PMID- 16785426
TI  - Visualization of a group II intron in the 23S rRNA of a stable ribosome.
AB  - Thousands of introns have been localized to rRNA genes throughout the three
      domains of life. The consequences of the presence of either a spliced or an
      unspliced intron in a rRNA for ribosome assembly and packaging are largely
      unknown. To help address these questions, and to begin an intron imaging study,
      we selected a member of the self-splicing group II intron family, which is
      hypothesized to be the progenitor not only of spliceosomal introns but also of
      non-LTR retrotransposons. We cloned the self-splicing group II Ll.LtrB intron
      from Lactococcus lactis into L. lactis 23S rRNA. The 2,492-nt Ll.LtrB intron
      comprises a catalytic core and an ORF, which encodes a protein, LtrA. LtrA forms
      a ribonucleoprotein (RNP) complex with the intron RNA to mediate splicing and
      mobility. The chimeric 23S-intron RNA was shown to be splicing proficient in its
      native host in the presence of LtrA. Furthermore, a low-resolution cryo-EM
      reconstruction of the L. lactis ribosome fused to the intron-LtrA RNP of a
      splicing-defective Ll.LtrB intron was obtained. The image revealed the intron as
      a large, well defined structure. The activity and structural integrity of the
      intron indicate not only that it can coexist with the ribosome but also that its
      presence permits the assembly of a stable ribosome. Additionally, we view our
      results as a proof of principle that ribosome chimeras may be generally useful
      for studying a wide variety of structured RNAs and RNP complexes that are not
      amenable to NMR, crystallographic, or single-particle cryo-EM methodologies.

PMID- 16785427
TI  - Involvement of human left dorsolateral prefrontal cortex in perceptual decision
      making is independent of response modality.
AB  - Perceptual decision making typically entails the processing of sensory signals,
      the formation of a decision, and the planning and execution of a motor response.
      Although recent studies in monkeys and humans have revealed possible neural
      mechanisms for perceptual decision making, much less is known about how the
      decision is subsequently transformed into a motor action and whether or not the
      decision is represented at an abstract level, i.e., independently of the specific
      motor response. To address this issue, we used functional MRI to monitor changes
      in brain activity while human subjects discriminated the direction of motion in
      random-dot visual stimuli that varied in coherence and responded with either
      button presses or saccadic eye movements. We hypothesized that areas representing
      decision variables should respond more to high- than to low-coherence stimuli
      independent of the motor system used to express a decision. Four areas were found
      that fulfilled this condition: left posterior dorsolateral prefrontal cortex
      (DLPFC), left posterior cingulate cortex, left inferior parietal lobule, and left
      fusifom/parahippocampal gyrus. We previously found that, when subjects made
      categorical decisions about degraded face and house stimuli, left posterior DLPFC
      showed a greater response to high- relative to low-coherence stimuli.
      Furthermore, the left posterior DLPFC appears to perform a comparison of signals
      from sensory processing areas during perceptual decision making. These data
      suggest that the involvement of left posterior DLPFC in perceptual decision
      making transcends both task and response specificity, thereby enabling a flexible
      link among sensory evidence, decision, and action.

PMID- 16785429
TI  - Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a
      furofuran lignan, (+)-sesamin.
AB  - (+)-Sesamin, a furofuran class lignan, is widespread in vascular plants and
      represented by Sesamum spp. (+)-Sesamin has been of rapidly growing interest
      because of its beneficial biological effects in mammals, but its biosynthesis and
      physiological roles in plants remain to be clarified. It is speculated to be
      synthesized from (+)-pinoresinol by means of (+)-piperitol by formation of two
      methylenedioxy bridges mediated by two distinct Sesamum indicum cytochrome P450
      (SiP450) proteins. Here, we report an SiP450, CYP81Q1, that alone catalyzes (+)
      sesamin biosynthesis from (+)-pinoresinol by means of (+)-piperitol by forming
      two methylenedioxy bridges. The CYP81Q1 gene expression profile was temporally
      consistent with the accumulation pattern of (+)-sesamin during seed development.
      The CYP81Q1-GFP chimera protein was colocalized with an endoplasmic reticulum
      (ER)-targeting chimera protein, indicating that (+)-sesamin biosynthesis occurs
      on the ER cytoplasmic surface. Moreover, we isolated two CYP81Q1 homologs from
      other Sesamum spp. Sesamum radiatum CYP81Q2 showed dual (+)-piperitol/(+)-sesamin
      synthetic activity. CYP81Q2, as well as CYP81Q1, therefore, corresponds to a (+)
      piperitol/(+)-sesamin synthase in lignan biosynthesis. In contrast, Sesamum
      alatum CYP81Q3 showed no activity, in accord with (+)-sesamin being deficient in
      S. alatum. Our findings not only provide insight into lignan biosynthesis but
      also unravel a unique mode of cytochrome P450 action.

PMID- 16785428
TI  - Phosphoproteomic analysis of Her2/neu signaling and inhibition.
AB  - Her2/neu (Her2) is a tyrosine kinase belonging to the EGF receptor (EGFR)/ErbB
      family and is overexpressed in 20-30% of human breast cancers. We sought to
      characterize Her2 signal transduction pathways further by using MS-based
      quantitative proteomics. Stably transfected cell lines overexpressing Her2 or
      empty vector were generated, and the effect of an EGFR and Her2 selective
      tyrosine kinase inhibitor, PD168393, on these cells was characterized.
      Quantitative measurements were obtained on 462 proteins by using the SILAC
      (stable isotope labeling with amino acids in cell culture) method to monitor
      three conditions simultaneously. Of these proteins, 198 showed a significant
      increase in tyrosine phosphorylation in Her2-overexpressing cells, and 81 showed
      a significant decrease in phosphorylation. Treatment of Her2-overexpressing cells
      with PD168393 showed rapid reversibility of the majority of the Her2-triggered
      phosphorylation events. Phosphoproteins that were identified included many known
      Her2 signaling molecules as well as known EGFR signaling proteins that had not
      been previously linked to Her2, such as Stat1, Dok1, and delta-catenin.
      Importantly, several previously uncharacterized Her2 signaling proteins were
      identified, including Axl tyrosine kinase, the adaptor protein Fyb, and the
      calcium-binding protein Pdcd-6/Alg-2. We also identified a phosphorylation site
      in Her2, Y877, which is located in the activation loop of the kinase domain, is
      distinct from the known C-terminal tail autophosphorylation sites, and may have
      important implications for regulation of Her2 signaling. Network modeling, which
      combined phosphoproteomic results with literature-curated protein-protein
      interaction data, was used to suggest roles for some of the previously
      unidentified Her2 signaling proteins.

PMID- 16785430
TI  - Extensive outcrossing and androdioecy in a vertebrate species that otherwise
      reproduces as a self-fertilizing hermaphrodite.
AB  - The mangrove killifish (Kryptolebias marmoratus) is the only vertebrate known to
      be capable of self-fertilization. Its gonad is typically an ovotestis that
      simultaneously produces eggs and sperm, and fertilization is internal. Although
      most populations of this species consist primarily or exclusively of
      hermaphroditic individuals, gonochoristic males occur at approximately 20%
      frequency in a natural population at Twin Cays, Belize. Here we use a battery of
      36 microsatellite loci to document a striking genetic pattern (high intraspecimen
      heterozygosities and low within-population linkage disequilibria) that differs
      qualitatively from the highly homozygous (or "clonal") genetic architecture
      characteristic of killifish populations previously studied in Florida, where
      males are much rarer. These findings document that outcrossing (probably between
      gonochoristic males and hermaphrodites) is common at the Belize site, and, more
      importantly, they demonstrate the dramatic impact that functional androdioecy can
      have on the population genetic architecture of this reproductively unique
      vertebrate species.

PMID- 16785432
TI  - Lanthanide complexes as fluorescent indicators for neutral sugars and cancer
      biomarkers.
AB  - Simple water-soluble lanthanum and europium complexes are effective at detecting
      neutral sugars as well as glycolipids and phospholipids. In solutions at
      physiologically relevant pH the fluorescent lanthanum complex binds neutral
      sugars with apparent binding constants comparable to those of arylboronic acids.
      Interference from commonly occurring anions is minimal. The europium complex
      detects sialic acid-containing gangliosides at pH 7.0 over an asialoganglioside.
      This selectivity is attributed, in large part, to the cooperative complexation of
      the oligosaccharide and sialic acid residues to the metal center, based on
      analogous prior studies. In MeOH, lysophosphatidic acid (LPA), a biomarker for
      several pathological conditions including ovarian cancer, is selectively detected
      by the europium complex. LPA is also detected via a fluorescence increase in
      human plasma samples. The 2-sn-OH moiety of LPA plays a key role in promoting
      binding to the metal center. Other molecules found in common brain ganglioside
      and phospholipid extracts do not interfere in the ganglioside or LPA fluorescence
      assays.

PMID- 16785431
TI  - Pegasoferae, an unexpected mammalian clade revealed by tracking ancient
      retroposon insertions.
AB  - Despite the recent large-scale efforts dedicated to comprehensive phylogenetic
      analyses using mitochondrial and nuclear DNA sequences, several relationships
      among mammalian orders remain controversial. Here, we present an extensive
      application of retroposon (L1) insertion analysis to the phylogenetic
      relationships among almost all mammalian orders. In addition to demonstrating the
      validity of Glires, Euarchontoglires, Laurasiatheria, and Boreoeutheria, we
      demonstrate an interordinal clade that links Chiroptera, Carnivora, and
      Perissodactyla within Laurasiatheria. Re-examination of a large DNA sequence data
      set yielded results consistent with our conclusion. We propose a superordinal
      name "Pegasoferae" for this clade of Chiroptera + Perissodactyla + Carnivora +
      Pholidota. The presence of a single incongruent L1 locus generates a tree in
      which the group of Carnivora + Perissodactyla associates with Cetartiodactyla but
      not with Chiroptera. This result suggests that incomplete lineage sorting of an
      ancestral dimorphism occurred with regard to the presence or absence of
      retroposon alleles in a common ancestor of Scrotifera (Pegasoferae +
      Cetartiodactyla), which was followed by rapid divergence into the extant orders
      over an evolutionarily short period. Accordingly, Euungulata (Cetartiodactyla +
      Perissodactyla) and Fereuungulata (Carnivora + Pholidota + Perissodactyla +
      Cetartiodactyla) cannot be validated as natural groups. The interordinal
      mammalian relationships presented here provide a cornerstone for future studies
      in the reconstruction of mammalian classifications, including extinct species, on
      evolution of large genomic sequences and structure, and in developmental analysis
      of morphological diversification.

PMID- 16785433
TI  - The cell surface leucine-rich repeat receptor for AtPep1, an endogenous peptide
      elicitor in Arabidopsis, is functional in transgenic tobacco cells.
AB  - AtPep1 is a 23-aa endogenous peptide elicitor from Arabidopsis leaves that
      signals the activation of components of the innate immune response against
      pathogens. Here, we report the isolation of an AtPep1 receptor from the surface
      of Arabidopsis suspension-cultured cells. An (125)I-labeled AtPep1 analog
      interacted with suspension-cultured Arabidopsis with a K(d) of 0.25 nM, and an
      (125)I-labeled azido-Cys-AtPep1 photoaffinity analog specifically labeled a
      membrane-associated protein of approximately 170 kDa. The labeled protein was
      purified to homogeneity, and its tryptic peptides were identified as gene
      At1g73080, which encodes a leucine-rich repeat receptor kinase, here called
      PEPR1. Verification of the binding protein as the receptor for AtPep1 was
      established by demonstrating the loss of function of microsomal membranes of two
      SALK insertional mutants and by a gain in function of the alkalinization response
      to AtPep1 by tobacco suspension-cultured cells expressing the At1g73080
      transgene. Synthetic homologs of AtPep1, deduced from the C termini of six known
      paralogs of PROPEP1, were biologically active and were competitors of the
      interaction of an AtPep1 radiolabeled analog with the receptor. The data are
      consistent with a role for PEPR1 as the receptor for AtPep1 to amplify innate
      immunity in response to pathogen attacks.

PMID- 16785434
TI  - An endogenous peptide signal in Arabidopsis activates components of the innate
      immune response.
AB  - Innate immunity is initiated in animals and plants through the recognition of a
      variety of pathogen-associated molecules that in animals are called pathogen
      associated molecular patterns and in plants are called elicitors. Some plant
      pathogen-derived elicitors have been identified as peptides, but peptide
      elicitors derived from the plant itself that activate defensive genes against
      pathogens have not been previously identified. Here, we report the isolation and
      characterization of a 23-aa peptide from Arabidopsis, called AtPep1, which
      activates transcription of the defensive gene defensin (PDF1.2) and activates the
      synthesis of H(2)O(2), both being components of the innate immune response. The
      peptide is derived from a 92-aa precursor encoded within a small gene that is
      inducible by wounding, methyl jasmonate, and ethylene. Constitutive expression of
      the AtPep1 precursor gene PROPEP1 in transgenic Arabidopsis plants causes a
      constitutive transcription of PDF1.2. When grown in soil, the transgenic plants
      exhibited an increased root development compared with WT plants and an enhanced
      resistance toward the root pathogen Pythium irregulare. Six paralogs of PROPEP1
      are present in Arabidopsis, and orthologs have been identified in species of
      several agriculturally important plant families, where they are of interest for
      their possible use in crop improvement.

PMID- 16785435
TI  - Low-dimensional, free-energy landscapes of protein-folding reactions by nonlinear
      dimensionality reduction.
AB  - The definition of reaction coordinates for the characterization of a protein
      folding reaction has long been a controversial issue, even for the "simple" case
      in which one single free-energy barrier separates the folded and unfolded
      ensemble. We propose a general approach to this problem to obtain a few
      collective coordinates by using nonlinear dimensionality reduction. We validate
      the usefulness of this method by characterizing the folding landscape associated
      with a coarse-grained protein model of src homology 3 as sampled by molecular
      dynamics simulations. The folding free-energy landscape projected on the few
      relevant coordinates emerging from the dimensionality reduction can correctly
      identify the transition-state ensemble of the reaction. The first embedding
      dimension efficiently captures the evolution of the folding process along the
      main folding route. These results clearly show that the proposed method can
      efficiently find a low-dimensional representation of a complex process such as
      protein folding.

PMID- 16785436
TI  - Hippocampal disconnection contributes to memory dysfunction in individuals at
      risk for Alzheimer's disease.
AB  - The concept of amnestic mild cognitive impairment (MCI) describes older people
      who show a decline predominantly in memory function, but who do not meet criteria
      for dementia. Because such individuals are at high risk for developing
      Alzheimer's disease, they are of great interest for understanding the prodromal
      stages of the disease process. The mechanism underlying memory dysfunction in
      people with MCI is not fully understood. The present study uses quantitative,
      high-resolution structural MRI techniques to investigate, in vivo, the anatomical
      substrate of memory dysfunction associated with MCI. Changes in brain structures
      were assessed with two imaging techniques: (i) whole-brain, voxel-based
      morphometry to determine regions of reduced white matter volume and (ii)
      sensitive volumetric segmentation of the entorhinal cortex and hippocampus, gray
      matter regions that are critically important for memory function. In participants
      with amnestic MCI, compared with age-matched controls, results showed a
      significant decrease in white matter volume in the region of the parahippocampal
      gyrus that includes the perforant path. There was also significant atrophy in
      both the entorhinal cortex and the hippocampus. Regression models demonstrated
      that both hippocampal volume and parahippocampal white matter volume were
      significant predictors of declarative memory performance. These results suggest
      that, in addition to hippocampal atrophy, disruption of parahippocampal white
      matter fibers contributes to memory decline in elderly individuals with MCI by
      partially disconnecting the hippocampus from incoming sensory information.

PMID- 16785437
TI  - Stargazin controls the pharmacology of AMPA receptor potentiators.
AB  - Glutamate is the major excitatory neurotransmitter in brain, and alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors
      (AMPARs) mediate the majority of postsynaptic depolarization. AMPAR ion channels
      display rapid gating, and their deactivation and desensitization determine the
      timing of synaptic transmission. AMPAR potentiators slow channel deactivation and
      desensitization, and these compounds represent exciting therapies for mental and
      neurodegenerative diseases. Previous studies showed that the AMPAR potentiators
      cyclothiazide and 4-[2-(phenylsulfonylamino)ethylthio]-2,6
      difluorophenoxyacetamide display a preference for flip and flop alternatively
      spliced versions of glutamate receptor subunits, respectively. Here, we find that
      the AMPAR auxiliary subunit stargazin changes this pharmacology and makes both
      spliced forms of glutamate receptor subunit 1 sensitive to both classes of
      potentiator. Stargazin also enhances the effect of AMPAR potentiators on channel
      deactivation. This work demonstrates that stargazin controls AMPAR potentiator
      pharmacology, which has important implications for development of AMPAR
      potentiators as therapeutic agents.

PMID- 16785438
TI  - Identifying and manipulating structural determinates linking catalytic
      specificities in terpene synthases.
AB  - Terpene synthases are a mechanistically intriguing family of enzymes that
      catalyze complex, multistep reactions that are capable of generating hundreds of
      structurally diverse hydrocarbon and oxygenated scaffolds of biological and
      commercial importance. Interestingly, distantly related terpene synthases from
      fungi to plants all contain an invariant three-dimensional fold, and molecular
      comparisons of their active sites indicate that they are enriched with relatively
      inert amino acid residues that do not react directly with the reaction
      intermediates. Therefore, catalytic specificity appears to rely on the contour
      and dynamics of the active site created by the positioning of amino acid
      backbones and side chains on this catalytic surface and by supporting layers of
      residues surrounding the synthase active site cavity. Despite the high degree of
      structural relatedness among terpene synthases, previous studies suggest that no
      clear relationship between phylogenic organization and catalytic specificities is
      easily deciphered. We now report on the reciprocal interconversion of catalytic
      specificities between two distinct yet evolutionarily related terpene synthases
      based on the systematic identification and mutational replacement of variable
      residues within and surrounding the active site. Furthermore, we uncover
      previously undocumented biosynthetic activity during the interconversion,
      activity that could have been present in a common ancestor of these two highly
      related synthases. These results provide a simplified means for mapping
      structural features that are responsible for functional attributes and a strategy
      for identifying residues that differentiate divergent biosynthetic properties in
      phylogenetically related terpene synthases.

PMID- 16785439
TI  - Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle
      contraction.
AB  - Muscle contraction and many other cell movements are driven by cyclic
      interactions between actin filaments and the motor enzyme myosin. Conformational
      changes in the actin-myosin binding interface occur in concert with the binding
      of ATP, binding to actin, and loss of hydrolytic by-products, but the effects of
      these conformational changes on the strength of the actomyosin bond are unknown.
      The force-dependent kinetics of the actomyosin bond may be particularly important
      at high loads, where myosin may detach from actin before achieving its full power
      stroke. Here we show that over a physiological range of rapidly applied loads,
      actomyosin behaves as a "catch" bond, characterized by increasing lifetimes with
      increasing loads up to a maximum at approximately 6 pN. Surprisingly, we found
      that the myosin-ADP bond is possessed of longer lifetimes under load than rigor
      bonds, although the load at which bond lifetime is maximal remains unchanged. We
      also found that actomyosin bond lifetime is ultimately dependent not only on
      load, but loading history as well. These data suggest a complex relationship
      between the rate of actomyosin dissociation and muscle force and shortening
      velocity. The 6-pN load for maximum bond lifetime is near the force generated by
      a single myosin molecule during isometric contraction. This raises the
      possibility that all catch bonds between load-bearing molecules are
      "mechanokinetically" tuned to their physiological environment.

PMID- 16785440
TI  - Discovery of a small-molecule HIV-1 integrase inhibitor-binding site.
AB  - Herein, we report the identification of a unique HIV-1 integrase (IN) inhibitor
      binding site using photoaffinity labeling and mass spectrometric analysis. We
      chemically incorporated a photo-activatable benzophenone moiety into a series of
      coumarin-containing IN inhibitors. A representative of this series was covalently
      photo-crosslinked with the IN core domain and subjected to HPLC purification.
      Fractions were subsequently analyzed by using MALDI-MS and electrospray
      ionization (ESI)-MS to identify photo-crosslinked products. In this fashion, a
      single binding site for an inhibitor located within the tryptic peptide
      (128)AACWWAGIK(136) was identified. Site-directed mutagenesis followed by in
      vitro inhibition assays resulted in the identification of two specific amino acid
      residues, C130 and W132, in which substitutions resulted in a marked resistance
      to the IN inhibitors. Docking studies suggested a specific disruption in
      functional oligomeric IN complex formation. The combined approach of photo
      affinity labeling/MS analysis with site-directed mutagenesis/molecular modeling
      is a powerful approach for elucidating inhibitor-binding sites of proteins at the
      atomic level. This approach is especially important for the study of proteins
      that are not amenable to traditional x-ray crystallography and NMR techniques.
      This type of structural information can help illuminate processes of inhibitor
      resistance and thereby facilitate the design of more potent second-generation
      inhibitors.

PMID- 16785441
TI  - Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell
      death in Drosophila melanogaster.
AB  - Ionizing radiation (IR) can induce apoptosis via p53, which is the most commonly
      mutated gene in human cancers. Loss of p53, however, can render cancer cells
      refractory to therapeutic effects of IR. Alternate p53-independent pathways exist
      but are not as well understood as p53-dependent apoptosis. Studies of how IR
      induces p53-independent cell death could benefit from the existence of a
      genetically tractable model. In Drosophila melanogaster, IR induces apoptosis in
      the imaginal discs of larvae, typically assayed at 4-6 hr after exposure to a
      LD(50) dose. In mutants of Drosophila Chk2 or p53 homologs, apoptosis is severely
      diminished in these assays, leading to the widely held belief that IR-induced
      apoptosis depends on these genes in Drosophila. In this article, we show that IR
      induced apoptosis still occurs in the imaginal discs of chk2 and p53 mutant
      larvae, albeit with a delay. We demonstrate that this phenomenon is a true
      apoptotic response because it requires caspase activity and the chromosomal locus
      that encodes the pro-apoptotic genes reaper, hid, and grim. We also show that
      Chk2- and p53-independent apoptosis is IR dose-dependent and is therefore
      probably triggered by a DNA damage signal. We conclude that Drosophila has Chk2-
      and p53-independent pathways to activate caspases and induce apoptosis in
      response to IR. This work establishes Drosophila as a model for p53-independent
      apoptosis, which is of potential therapeutic importance for inducing cell death
      in p53-deficient cancer cells.

PMID- 16785442
TI  - Linking DNA-binding proteins to their recognition sequences by using protein
      microarrays.
AB  - Analyses of whole-genome sequences and experimental data sets have revealed a
      large number of DNA sequence motifs that are conserved in many species and may be
      functional. However, methods of sufficient scale to explore the roles of these
      elements are lacking. We describe the use of protein arrays to identify proteins
      that bind to DNA sequences of interest. A microarray of 282 known and potential
      yeast transcription factors was produced and probed with oligonucleotides of
      evolutionarily conserved sequences that are potentially functional. Transcription
      factors that bound to specific DNA sequences were identified. One previously
      uncharacterized DNA-binding protein, Yjl103, was characterized in detail. We
      defined the binding site for this protein and identified a number of its target
      genes, many of which are involved in stress response and oxidative
      phosphorylation. Protein microarrays offer a high-throughput method for
      determining DNA-protein interactions.

PMID- 16785443
TI  - ICP0 and the US3 protein kinase of herpes simplex virus 1 independently block
      histone deacetylation to enable gene expression.
AB  - SK-N-SH cells exposed to low ratios of ICP0-null (DeltaICP0) mutants of herpes
      simplex virus per cell express the viral alpha proteins, but the progression to
      beta and gamma gene expression does not ensue. In these restrictive cells, post
      alpha gene expression can be induced after exposure of the infected cells to
      sodium butyrate, an indication that VP16 brought into cells by the virus and the
      alpha gene products made after infection cannot block the silencing of viral post
      alpha genes by histone deacetylases (HDACs). This observation is consistent with
      evidence reported earlier that ICP0 dissociates HDAC1/2 from the CoREST/REST
      complex. In permissive U2OS cells, replication is independent of the ratio of
      DeltaICP0 mutant per cell. To determine whether other viral genes are involved in
      blocking HDACs, we used a surrogate system consisting of baculoviruses carrying
      viral or cellular genes driven by CMV immediate-early promoter. Expression of
      these genes requires blocking of histone deacetylation. We report that (i)
      cotransduced U(S)3 or U(S)3.5 protein kinase substitutes for sodium butyrate in
      enabling the expression of a reporter gene in restrictive cells and enhancing it
      in permissive cells; (ii) HDAC1 is phosphorylated concomitant with the expression
      of reporter genes; and (iii) the amounts and appearance of HDAC1 are altered in
      transduced cells expressing U(S)3 protein kinase in the absence of other viral
      proteins. We conclude that the U(S)3 protein kinase blocks histone deacetylation
      by a mechanism distinct from that of ICP0 and that debilitated histone
      deacetylation contributes to the permissiveness of U2OS cells for DeltaICP0
      mutants.

PMID- 16785444
TI  - Modeling the Lac repressor-operator assembly: the influence of DNA looping on Lac
      repressor conformation.
AB  - Repression of transcription of the Escherichia coli Lac operon by the Lac
      repressor (LacR) is accompanied by the simultaneous binding of LacR to two
      operators and the formation of a DNA loop. A recently developed theory of
      sequence-dependent DNA elasticity enables one to relate the fine structure of the
      LacR-DNA complex to a wide range of heretofore-unconnected experimental
      observations. Here, that theory is used to calculate the configuration and free
      energy of the DNA loop as a function of its length and base-pair sequence, its
      linking number, and the end conditions imposed by the LacR tetramer. The tetramer
      can assume two types of conformations. Whereas a rigid V-shaped structure is
      observed in the crystal, EM images show extended forms in which two dimer
      subunits are flexibly joined. Upon comparing our computed loop configurations
      with published experimental observations of permanganate sensitivities, DNase I
      cutting patterns, and loop stabilities, we conclude that linear DNA segments of
      short-to-medium chain length (50-180 bp) give rise to loops with the extended
      form of LacR and that loops formed within negatively supercoiled plasmids induce
      the V-shaped structure.

PMID- 16785445
TI  - Molecular basis for PKR activation by PACT or dsRNA.
AB  - The mammalian protein kinase PKR is a critical component of the innate immune
      response against virus infection. Its cellular actions are mediated by modulating
      cell signaling and translational regulation. To be enzymatically active, latent
      PKR needs to be activated by binding to one of its activators, dsRNA or PACT
      protein. Although the structures of the N-terminal dsRNA-binding domain and the C
      terminal kinase domain of PKR have been separately determined, the mode of
      activation of the enzyme remains unknown. To address this problem, we used
      biochemical, genetic, and NMR analyses to identify the PACT-binding motif (PBM)
      located in the kinase domain and demonstrated an intramolecular interaction
      between PBM and dsRNA-binding domain. This interaction is responsible for keeping
      PKR in an inactive conformation, because its disruption by point mutations of
      appropriate residues produced constitutively active PKR. Furthermore, a short
      decoy peptide, representing PBM, was able to activate PKR by interfering with the
      intramolecular interaction. These observations suggest a model for PKR activation
      upon binding of dsRNA or PACT.

PMID- 16785448
TI  - Editorial policy: industry funding and editorial independence.

PMID- 16785447
TI  - The guinea pig as a transmission model for human influenza viruses.
AB  - The severity of epidemic and pandemic influenza outbreaks is dictated in part by
      the efficiency with which the causative strain transmits between human hosts. The
      mechanisms underlying influenza virus spread are poorly understood, in part
      because of the lack of a convenient animal model to study this phenomenon.
      Indeed, despite extremely efficient transmission among humans and virulence in
      the mouse model, we have shown that even the 1918 pandemic influenza virus does
      not transmit between mice. We therefore evaluated the guinea pig as a model
      mammalian host for influenza virus. Using the recent human isolate
      A/Panama/2007/99 (Pan/99) (H3N2) virus, we found that guinea pigs were highly
      susceptible to infection with the unadapted virus (ID(50) = 5 plaque-forming
      units). Pan/99 virus grew to high titers in the upper respiratory tract and was
      shed in nasal washings of infected animals. Moreover, influenza virus was
      transmitted from infected guinea pigs to noninfected guinea pigs housed in the
      same cage, an adjacent cage, and a cage placed 91 cm away. Our results
      demonstrate that influenza virus can pass between guinea pigs by means of droplet
      spread and thereby establish the suitability of the guinea pig as a model host
      for influenza virus transmission studies.

PMID- 16785449
TI  - Task Force Two calls for pan-Canadian approach to physician resources.

PMID- 16785450
TI  - Chronic malnutrition grips western Nepal.

PMID- 16785446
TI  - The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts
      directly with caspase-1 to modulate IL-1beta production.
AB  - Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory
      disorder with high carrier frequencies in the Middle East. Pyrin, the protein
      mutated in FMF, regulates caspase-1 activation and consequently IL-1beta
      production through cognate interaction of its N-terminal PYRIN motif with the ASC
      adaptor protein. However, the preponderance of mutations reside in pyrin's C
      terminal B30.2 domain. Here we demonstrate direct interaction of this domain with
      caspase-1. In lysates from cells not expressing ASC, reciprocal GST pull-downs
      demonstrated the interaction of pyrin with the p20 and p10 catalytic subunits of
      caspase-1. Coimmunoprecipitations of pyrin and caspase-1 from THP-1 human
      monocytic cells were consistent with the interaction of endogenous proteins. The
      C-terminal B30.2 domain of pyrin is necessary and sufficient for the interaction,
      and binding was reduced by FMF-associated B30.2 mutations. Full-length pyrin
      attenuated IL-1beta production in cells transfected with a caspase-1/IL-1beta
      construct, an effect diminished by FMF-associated B30.2 mutations and in B30.2
      deletion mutants. Modeling of the crystal structure of caspase-1 with the deduced
      structure of the pyrin B30.2 domain corroborated both the interaction and the
      importance of M694V and M680I pyrin mutations. Consistent with a net inhibitory
      effect of pyrin on IL-1beta activation, small interfering RNA (siRNA)-mediated
      pyrin knockdown in THP-1 cells augmented IL-1beta production in response to
      bacterial LPS. Moreover, the IL-1 receptor antagonist anakinra suppressed acute
      phase proteins in a patient with FMF and amyloidosis. Our data support a direct,
      ASC-independent effect of pyrin on IL-1beta activation and suggest heightened IL
      1 responsiveness as one factor selecting for pyrin mutations.

PMID- 16785451
TI  - Alberta health reforms shelved, again.

PMID- 16785452
TI  - Darfur on life-support: MSF.

PMID- 16785453
TI  - Happy doctors? Balancing professional and personal commitments.

PMID- 16785454
TI  - Microvascular dysfunction in cardiac syndrome X: the role of inflammation.

PMID- 16785455
TI  - Buprenorphine: a potential new treatment option for opioid dependence.

PMID- 16785456
TI  - Malnutrition: a silent emergency.

PMID- 16785457
TI  - A case of myocardial infarction complicating Kawasaki disease.

PMID- 16785458
TI  - Pulmonary hypertension following L-lysine ibuprofen therapy in a preterm infant
      with patent ductus arteriosus.
AB  - Patent ductus arteriosus is one of the most common congenital abnormalities found
      in premature infants. Ibuprofen, a nonsteroidal drug that is commonly used as an
      antipyretic, analgesic and anti-inflammatory agent, is also used to induce
      closure of symptomatic patent ductus arteriosus in preterm infants. Recently, we
      gave L-lysine ibuprofen to a preterm infant with respiratory distress to induce
      closure of a patent ductus arteriosus, and the infant experienced pulmonary
      hypertension. Only 3 cases of pulmonary hypertension following early
      administration of an ibuprofen solution buffered with tromethamine have
      previously been reported. However, this severe side effect has never been
      observed in multicentre, randomized, double-blind controlled trials, nor in
      recent reviews or meta-analyses of L-lysine ibuprofen use.

PMID- 16785459
TI  - Cost-effectiveness of self-managed versus physician-managed oral anticoagulation
      therapy.
AB  - BACKGROUND: Patient self-management of long-term oral anticoagulation therapy is
      an effective strategy in a number of clinical situations, but it is currently not
      a funded option in the Canadian health care system. We sought to compare the
      incremental cost and health benefits of self-management with those of physician
      management from the perspective of the Canadian health care payer over a 5-year
      period. METHODS: We developed a Bayesian Markov model comparing the costs and
      quality-adjusted life years (QALYs) accrued to patients receiving oral
      anticoagulation therapy through self-management or physician management for
      atrial fibrillation or for a mechanical heart valve. Five health states were
      defined: no events, minor hemorrhagic events, major hemorrhagic events,
      thrombotic events and death. Data from published literature were used for
      transition probabilities. Canadian 2003 costs were used, and utility estimates
      were obtained from various published sources. RESULTS: Self-management resulted
      in 3.50 fewer thrombotic events, 0.78 fewer major hemorrhagic events and 0.12
      fewer deaths per 100 patients than physician management. The average discounted
      incremental cost of self-management over physician management was found to be 989
      dollars (95% confidence interval [CI] 310 dollars-1655 dollars) per patient and
      the incremental QALYs gained was 0.07 (95% CI 0.06-0.08). The cost-effectiveness
      of self-management was 14,129 dollars per QALY gained. There was a 95% chance
      that self-management would be cost-effective at a willingness to pay of 23,800
      dollars per QALY. Results were robust in probabilistic and deterministic
      sensitivity analyses. INTERPRETATION: This model suggests that self-management is
      a cost-effective strategy for those receiving long-term oral anticoagulation
      therapy for atrial fibrillation or for a mechanical heart valve.

PMID- 16785460
TI  - Re-examining our approach to the approval and use of new drugs.

PMID- 16785461
TI  - Evidence and advocacy: are all things considered?

PMID- 16785463
TI  - Views of medicine as a profession.

PMID- 16785464
TI  - Views of medicine as a profession.

PMID- 16785462
TI  - Sudden infant death syndrome.
AB  - Sudden infant death syndrome (SIDS) continues to be the most common cause of
      postneonatal infant death. SIDS is a complex, multifactorial disorder, the cause
      of which is still not fully understood. However, much is known now about
      environmental risk factors, some of which are modifiable. These include maternal
      and antenatal risk factors such as smoking during pregnancy, as well as infant
      related risk factors such as non-supine sleeping position and soft bedding.
      Emerging evidence also substantiates an expanding number of genetic risk factors.
      Interactions between environmental and genetic risk factors may be of critical
      importance in determining an infant's actual risk of SIDS. Although no practical
      way exists to identify which infants will die of SIDS, nor is there a safe and
      proven prevention strategy even if identification were feasible, reducing
      exposure to modifiable risk factors has helped to lower the incidence of SIDS.
      Current challenges include wider dissemination of guidelines to all people who
      care for infants, dissemination of guidelines in culturally appropriate ways, and
      surveillance of SIDS trends and other outcomes associated with implementation of
      these guidelines.

PMID- 16785465
TI  - ALPHA form: additional resources.

PMID- 16785466
TI  - Wait times in the real world.

PMID- 16785467
TI  - Views of medicine as a profession.

PMID- 16785468
TI  - Patient characteristics not described.

PMID- 16785469
TI  - Views of medicine as a profession.

PMID- 16785470
TI  - Gefitinib for epidermal growth factor receptor mutant lung cancers: searching for
      a weapon of mass destruction.

PMID- 16785471
TI  - Prospective phase II study of gefitinib for chemotherapy-naive patients with
      advanced non-small-cell lung cancer with epidermal growth factor receptor gene
      mutations.
AB  - PURPOSE: This study was undertaken to investigate the efficacy and the
      feasibility of gefitinib for chemotherapy-naive patients with advanced non-small
      cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)
      mutations. PATIENTS AND METHODS: The EGFR gene status in various tumor samples
      obtained from chemotherapy-naive advanced NSCLC patients was examined by DNA
      sequencing of EGFR exons 18 to 23. Patients harboring EGFR mutations received
      gefitinib (250 mg/d) alone. The response rate, progression-free survival (PFS),
      and toxicity profile were assessed prospectively. RESULTS: Between June 2004 and
      October 2005, 75 patients were examined for the EGFR status, and 25 patients
      (33%) harbored EGFR mutations. EGFR mutations were significantly frequent in
      females (P < .01) and never or light smokers (P < .001). Sixteen patients with
      EGFR mutations were enrolled onto the study. The overall response rate in these
      patients was 75% (95% CI, 54% to 96%), and the disease control rate was 88% (95%
      CI, 71% to 100%). The median PFS time of these patients was 9.7 months (95% CI,
      7.4 to 9.9 months). No life-threatening toxicity was observed. CONCLUSION:
      Treatment with gefitinib alone for chemotherapy-naive NSCLC patients with EGFR
      mutations could achieve a high efficacy with acceptable toxicity. To assess the
      proper timing of gefitinib in such patients, a subsequent randomized trial
      comparing gefitinib with standard chemotherapy is warranted.

PMID- 16785472
TI  - Genetic variations in radiation and chemotherapy drug action pathways predict
      clinical outcomes in esophageal cancer.
AB  - PURPOSE: Understanding how specific genetic variants modify drug action pathways
      may provide informative blueprints for individualized chemotherapy. METHODS: We
      applied a pathway-based approach to examine the impact of a comprehensive panel
      of genetic polymorphisms on clinical outcomes in 210 esophageal cancer patients.
      RESULTS: In the Cox proportional hazards model, MTHFR Glu429Ala variant genotypes
      were associated with significantly improved survival (hazard ratio [HR] = 0.56;
      95% CI, 0.35 to 0.89) in patients treated with fluorouracil (FU). The 3-year
      survival rates for patients with the variant genotypes and the wild genotypes
      were 65.26% and 46.43%, respectively. Joint analysis of five polymorphisms in
      three FU pathway genes showed a significant trend for reduced recurrence risk and
      longer recurrence-free survival as the number of adverse alleles decreased (P =
      .004). For patients receiving platinum drugs, the MDR1 C3435T variant allele was
      associated with significantly reduced recurrence risk (HR = 0.25; 95% CI, 0.10 to
      0.64) and improved survival (HR = 0.44; 95% CI, 0.23 to 0.85). In nucleotide
      excision repair genes, there was a significant trend for a decreasing risk of
      death with a decreasing number of high-risk alleles (P for trend = .0008). In
      base excision repair genes, the variant alleles of XRCC1 Arg399Gln were
      significantly associated with the absence of pathologic complete response (odds
      ratio = 2.75; 95% CI, 1.14 to 6.12) and poor survival (HR = 1.92; 95% CI, 1.00 to
      3.72). CONCLUSION: Several biologically plausible associations between individual
      single nucleotide polymorphisms and clinical outcomes were found. Our data also
      strongly suggest that combined pathway-based analysis may provide valuable
      prognostic markers of clinical outcomes.

PMID- 16785473
TI  - Summaries for patients. Abatacept for people with active rheumatoid arthritis.

PMID- 16785474
TI  - Summaries for patients. What are the risks of using inhaled long-acting beta
      agonist medications for the relief of asthma?

PMID- 16785475
TI  - Effects of abatacept in patients with methotrexate-resistant active rheumatoid
      arthritis: a randomized trial.
AB  - BACKGROUND: The selective co-stimulation modulator abatacept demonstrated
      efficacy for treating rheumatoid arthritis in early clinical studies. OBJECTIVE:
      To evaluate the effects of abatacept in patients with persistent, active
      rheumatoid arthritis despite methotrexate treatment. DESIGN: One-year,
      multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to
      October 2004). SETTING: 116 centers worldwide. PATIENTS: 652 patients with active
      rheumatoid arthritis despite methotrexate treatment. INTERVENTION: Once-monthly
      infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or
      placebo. MEASUREMENTS: Co-primary end points were a 20% improvement in American
      College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically
      meaningful improvements in physical function, and change from baseline in joint
      erosion score at 1 year. RESULTS: Four hundred thirty-three and 219 patients were
      randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162
      (74%), respectively, completed 1 year of treatment. In a modified intention-to
      treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for
      abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI,
      19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo
      (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and
      19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points
      [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses
      increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4
      percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept
      versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5
      percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference,
      22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P <
      0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of
      patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the
      progression of structural joint damage compared with placebo. Abatacept-treated
      patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference,
      3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence
      of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage
      points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8%
      vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points];
      peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to
      14.0 percentage points]) compared with placebo recipients. LIMITATIONS: The study
      involved only 1 group of patients over 1 year. CONCLUSIONS: Abatacept
      statistically significantly reduced disease activity in patients with rheumatoid
      arthritis and an inadequate response to methotrexate. Longer treatment in
      different patient populations is needed to establish its appropriate role in
      rheumatoid arthritis.

PMID- 16785476
TI  - Autoimmune diseases in asthma.
AB  - BACKGROUND: Previous research has suggested an inverse relationship between T
      helper 2-related atopic disorders, such as asthma, and T-helper 1-related
      autoimmune diseases. One controversial hypothesis postulates that asthma provides
      a protective effect for the development of autoimmune-related disorders.
      OBJECTIVE: To assess the rate of newly diagnosed autoimmune disorders in a large
      cohort of young adults. DESIGN: Using cross-sectional data from the Israeli
      Defense Force database, the authors analyzed the prevalence of autoimmune
      disorders in asthmatic and nonasthmatic military personnel between 1980 and 2003.
      A follow-up study traced newly diagnosed autoimmune disorders among asthmatic and
      nonasthmatic individuals from the time of enrollment in military service until
      discharge (22 and 36 months for women and men, respectively). SETTING: General
      community. PATIENTS: 307,367 male and 181,474 female soldiers in compulsory
      military service who were between 18 and 21 years of age. MEASUREMENTS: Cases of
      type 1 diabetes mellitus, vasculitis, immune thrombocytopenic purpura,
      inflammatory bowel disease, rheumatoid arthritis, and the antiphospholipid
      syndrome. RESULTS: Of 488,841 participants at enrollment, significantly more
      women than men had autoimmune disorders. Compared with asthmatic women,
      nonasthmatic women had a significantly higher prevalence of all autoimmune
      disorders except for the antiphospholipid syndrome. Type 1 diabetes mellitus,
      vasculitis, and rheumatoid arthritis were less prevalent in men with asthma than
      in those without. During the follow-up period, vasculitis and rheumatoid
      arthritis were more frequently diagnosed in nonasthmatic persons of both sexes.
      There was a significantly higher incidence of immune thrombocytopenic purpura,
      inflammatory bowel disease, and the antiphospholipid syndrome in nonasthmatic
      women and a statistically significantly higher incidence of type 1 diabetes
      mellitus in nonasthmatic men. LIMITATIONS: The study was limited to a population
      of young military recruits; therefore, its findings are not necessarily
      applicable to the general population. Because of the noninterventional nature of
      the study, it describes associations but cannot prove causality. CONCLUSIONS:
      Asthma status may affect the prevalence of major autoimmune disorders.
      Preexisting asthma seems to protect against the development of autoimmune
      disorders to varying degrees in men and women.

PMID- 16785477
TI  - Dogma disputed: can aggressively lowering blood pressure in hypertensive patients
      with coronary artery disease be dangerous?
AB  - BACKGROUND: Because coronary perfusion occurs mainly during diastole, patients
      with coronary artery disease (CAD) could be at increased risk for coronary events
      if diastolic pressure falls below critical levels. OBJECTIVE: To determine
      whether low blood pressure could be associated with excess mortality and
      morbidity in this population. DESIGN: A secondary analysis of data from the
      International Verapamil-Trandolapril Study (INVEST), which was conducted from
      September 1997 to February 2003. SETTING: 862 sites in 14 countries. PATIENTS: 22
      576 patients with hypertension and CAD. INTERVENTIONS: Patients from INVEST were
      randomly assigned to a verapamil sustained-release- or atenolol-based strategy;
      blood pressure control and outcomes were equivalent. MEASUREMENTS: An unadjusted
      quadratic proportional hazards model was used to evaluate the relationship
      between average on-treatment blood pressure and risk for the primary outcome (all
      cause death, nonfatal stroke, and nonfatal myocardial infarction [MI]), all-cause
      death, total MI, and total stroke. A second model adjusted for differences in
      baseline covariates. RESULTS: The relationship between blood pressure and the
      primary outcome, all-cause death, and total MI was J-shaped, particularly for
      diastolic pressure, with a nadir at 119/84 mm Hg. After adjustment, the J-shaped
      relationship persisted between diastolic pressure and primary outcome. The MI
      stroke ratio remained constant over a wide blood pressure range, but at a lower
      diastolic blood pressure, there were substantially more MIs than strokes. An
      interaction between decreased diastolic pressure and history of revascularization
      was observed; low diastolic pressure was associated with a relatively lower risk
      for the primary outcome in patients with revascularization than in those without
      revascularization. LIMITATIONS: This is a post hoc analysis of hypertensive
      patients with CAD. CONCLUSIONS: The risk for the primary outcome, all-cause
      death, and MI, but not stroke, progressively increased with low diastolic blood
      pressure. Excessive reduction in diastolic pressure should be avoided in patients
      with CAD who are being treated for hypertension.

PMID- 16785478
TI  - Quality of care for patients hospitalized for acute exacerbations of chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is
      1 of the 10 leading causes of hospitalization among adults in the United States.
      OBJECTIVE: To evaluate the quality of care provided to patients hospitalized for
      acute exacerbations of COPD and to determine whether hospital or patient
      characteristics influence treatment. DESIGN: Retrospective cohort study. SETTING:
      360 hospitals throughout the United States. PATIENTS: 69,820 patients
      hospitalized for acute exacerbations of COPD. MEASUREMENTS: Adherence to
      diagnosis and treatment recommendations contained in guidelines produced by the
      American College of Physicians and the American College of Chest Physicians;
      analyses of associations between hospital and patient characteristics and
      composite measures of performance. RESULTS: Of the 69,820 patients, 66,276 (95%)
      underwent chest radiography, 63,715 (91%) received supplemental oxygen, 67 515
      (97%) received bronchodilators, 59,240 (85%) received systemic steroids, and
      59,053 (85%) were given antibiotics. In total, 45,800 (66%) received this entire
      set of recommended care processes. Numerous participants received tests or
      treatments that were not beneficial: 16,607 (24%) were treated with
      methylxanthine bronchodilators, 10,051 (14%) had sputum testing, 8354 (12%)
      underwent acute spirometry, 4299 (6%) had chest physiotherapy, and 1409 (2%) were
      treated with mucolytic medications. Overall, 31,519 patients (45%) received at
      least 1 of these nonrecommended care elements, and 22,929 (33%) received ideal
      care, defined as all of the recommended care processes and none of the
      nonrecommended ones. Individual hospital performance varied widely; whereas older
      patients and women were more likely to receive ideal care than their
      counterparts, a higher annual volume of admissions for COPD was not associated
      with improved hospital performance. LIMITATIONS: The study used administrative
      data, not chart review, and was limited to the inpatient management of COPD.
      CONCLUSIONS: The quality of care for patients hospitalized for acute
      exacerbations of COPD may be improved by increasing the use of systemic
      corticosteroid and antibiotic therapy, decreasing the use of unnecessary and
      potentially harmful treatments, and reducing variation in practice across
      hospitals.

PMID- 16785479
TI  - Narrative review: drug-eluting stents for the management of restenosis: a
      critical appraisal of the evidence.
AB  - Interventional cardiologists have quickly replaced bare metal stents with
      intravascular drug-eluting stents for treating and preventing restenosis, largely
      on the basis of empirical evidence that shows profound reduction in angiographic
      and clinical restenosis. A critical reassessment of the published evidence,
      however, suggests that the putative superiority of intravascular drug-eluting
      stents is founded on questionable premises, including 1) overestimation of
      restenosis benefit, 2) underestimation of the risk for stent thrombosis, 3)
      overreliance on "soft" rather than "hard" outcomes (need for repeated
      revascularization vs. death or myocardial infarction), and 4) the attendant
      overestimation of cost-effectiveness. Because the long-term incremental risks,
      benefits, and costs of drug-eluting stents have not yet been optimally evaluated
      in a broad spectrum of patient and lesion cohorts, the rational role of these
      devices in clinical management warrants reappraisal.

PMID- 16785480
TI  - Redesigning residency education in internal medicine: a position paper from the
      Association of Program Directors in Internal Medicine.
AB  - There has been considerable change in the practice of internal medicine in the
      past quarter century, including the rise of specialization, increasing time
      pressure, the hospitalist movement, and the rapidly changing responsibilities of
      internists in inpatient and outpatient settings. Training programs have not
      adequately responded to these trends, and there is a consensus that the residency
      education system urgently needs redesign.

PMID- 16785481
TI  - Abatacept in rheumatoid arthritis: a new branch on the "biologics" tree.

PMID- 16785482
TI  - Internal medicine training: putt or get off the green.

PMID- 16785484
TI  - The value of physician assessment.

PMID- 16785485
TI  - Chagasic encephalitis as the initial manifestation of AIDS.

PMID- 16785486
TI  - Quicksilver cholecystitis.

PMID- 16785487
TI  - The rocky road to useful cancer biomarkers.

PMID- 16785488
TI  - Homing in on L-selectin.

PMID- 16785489
TI  - A cell-surface molecule involved in organ-specific homing of lymphocytes. 1983.

PMID- 16785490
TI  - Intracellular TLR signaling: a structural perspective on human disease.
AB  - TLRs are crucial sensors of microbial infection. Maintaining structural integrity
      of TLR signaling components is essential for subsequent immunological protection.
      Alterations to the structure of these signaling molecules are often associated
      with profound clinical outcomes and susceptibility to various infectious
      diseases. These changes in structure are sometimes the result of a single
      nucleotide polymorphism (SNP). Numerous SNPs have been found in components of the
      TLR signaling pathway. Recently, the medical consequences and effects on TLR
      signaling of several of these SNPs have been elucidated. In addition, there have
      been numerous structures solved that are important to our understanding of the
      TLR signaling pathway at the molecular level. The scope of this review is to tie
      together current structural, biochemical, and genetic information of TLR
      signaling.

PMID- 16785491
TI  - Cutting edge: the silent chemokine receptor D6 is required for generating T cell
      responses that mediate experimental autoimmune encephalomyelitis.
AB  - D6, a promiscuous nonsignaling chemokine binding molecule expressed on the
      lymphatic endothelium, internalizes and degrades CC chemokines, and D6(-/-) mice
      demonstrated increased cutaneous inflammation following topical phorbol ester or
      CFA injection. We report that D6(-/-) mice were unexpectedly resistant to the
      induction of experimental autoimmune encephalomyelitis due to impaired
      encephalitogenic responses. Following induction with myelin oligodendroglial
      glycoprotein (MOG) peptide 35-55 in CFA, D6(-/-) mice showed reduced spinal cord
      inflammation and demyelination with lower incidence and severity of experimental
      autoimmune encephalomyelitis attacks as compared with D6(+/+) littermates. In
      adoptive transfer studies, MOG-primed D6(+/-) T cells equally mediated disease in
      D6(+/+) or D6(-/-) mice, whereas cells from D6(-/-) mice transferred disease
      poorly to D6(+/-) recipients. Lymph node cells from MOG-primed D6(-/-) mice
      showed weak proliferative responses and made reduced IFN-gamma but normal IL-5.
      CD11c(+) dendritic cells accumulated abnormally in cutaneous immunization sites
      of D6(-/-) mice. Surprisingly, D6, a "silent" chemokine receptor, supports immune
      response generation.

PMID- 16785492
TI  - Cutting edge: STAT1 and T-bet play distinct roles in determining outcome of
      visceral leishmaniasis caused by Leishmania donovani.
AB  - T-bet and STAT1 regulate IFN-gamma gene transcription in CD4+ T cells, which
      mediate protection against Leishmania. Here we show that T-bet and STAT1 are
      required for the induction of an efficient Th1 response during Leishmania
      donovani infection, but they play distinct roles in determining disease outcome.
      Both STAT1(-/-) and T-bet(-/-) mice failed to mount a Th1 response, but STAT1(-/
      ) mice were highly resistant to L. donovani and developed less immunopathology,
      whereas T-bet(-/-) mice were highly susceptible and eventually developed liver
      inflammation. Adoptive cell transfer studies showed that RAG2(-/-) recipients
      receiving STAT1(+/+) or STAT1(-/-) T cells developed comparable liver pathology,
      but those receiving STAT1(-/-) T cells were significantly more susceptible to
      infection. These unexpected findings reveal distinct roles for T-bet and STAT1 in
      mediating host immunity and liver pathology during visceral leishmaniasis.

PMID- 16785493
TI  - Cutting edge: impaired glycosphingolipid trafficking and NKT cell development in
      mice lacking Niemann-Pick type C1 protein.
AB  - Niemann-Pick type C1 (NPC1) is a late endosomal/lysosomal transmembrane protein
      involved in the cellular transport of glycosphingolipids and cholesterol that is
      mutated in a majority of patients with Niemann-Pick C neurodegenerative disease.
      We found that NPC1-deficient mice lacked Valpha14-Jalpha18 NKT cells, a major
      population of CD1d-restricted T cells that is conserved in humans. NPC1-deficient
      mice also exhibited marked defects in the presentation of Sphingomonas cell wall
      Ags to NKT cells and in bacterial clearance in vivo. A synthetic fluorescent
      alpha-glycosylceramide analog of the Sphingomonas Ag trafficked to the lysosome
      of wild-type cells but accumulated in the late endosome of NPC1-deficient cells.
      These findings reveal a blockade of lipid trafficking between endosome and
      lysosome as a consequence of NPC1 deficiency and suggest a common mechanism for
      the defects in lipid presentation and development of Valpha14-Jalpha18 NKT cells.

PMID- 16785494
TI  - Cutting edge: dendritic cells are essential for in vivo IL-12 production and
      development of resistance against Toxoplasma gondii infection in mice.
AB  - A powerful IFN-gamma response is triggered upon infection with the protozoan
      parasite, Toxoplasma gondii. Several cell populations, including dendritic cells
      (DCs), macrophages, and neutrophils, produce IL-12, a key cytokine for IFN-gamma
      induction. However, it is still unclear which of the above cell populations is
      its main source. Diphtheria toxin (DT) injection causes transient DC depletion in
      a transgenic mouse expressing Simian DT receptors under the control of the CD11c
      promoter, allowing us to investigate the role of DCs in IL-12 production. T.
      gondii-inoculated DT-treated and control groups were monitored for IL-12 levels
      and survival. We show in this study that DC depletion abolished IL-12 production
      and led to mortality. Furthermore, replenishment with wild-type, but not MyD88-
      or IL-12p35-deficient, DCs rescued IL-12 production, IFN-gamma-induction, and
      resistance to infection in DC-depleted mice. Taken together, the results
      presented in this study indicate that DCs constitute the major IL-12-producing
      cell population in vivo during T. gondii infection.

PMID- 16785495
TI  - Cutting edge: interleukin 17 signals through a heteromeric receptor complex.
AB  - IL-17 is an inflammatory cytokine produced primarily by a unique lineage of CD4 T
      cells that plays critical roles in the pathogenesis of multiple autoimmune
      diseases. IL-17RA is a ubiquitously expressed receptor that is essential for IL
      17 biologic activity. Despite widespread receptor expression, the activity of IL
      17 is most classically defined by its ability to induce the expression of
      inflammatory cytokines, chemokines, and other mediators by stromal cells. The
      lack of IL-17 responsiveness in mouse stromal cells genetically deficient in IL
      17RA is poorly complemented by human IL-17RA, suggesting the presence of an
      obligate ancillary component whose activity is species specific. This component
      is IL-17RC, a distinct member of the IL-17R family. Thus, the biologic activity
      of IL-17 is dependent on a complex composed of IL-17RA and IL-17RC, suggesting a
      new paradigm for understanding the interactions between the expanded family of IL
      17 ligands and their receptors.

PMID- 16785496
TI  - Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode
      for regulatory T cells.
AB  - Multiple modes of suppressive mechanisms including IL-10 are thought to be
      implicated in CD4+CD25+ regulatory T (Treg) cell-mediated suppression. However,
      the cellular source, role, and molecular mechanism of IL-10 in Treg cell biology
      remain controversial. We now studied the interaction between Treg cells and APCs.
      We demonstrate that Treg cells, but not conventional T cells, trigger high levels
      of IL-10 production by APCs, stimulate APC B7-H4 expression, and render APCs
      immunosuppressive. Initial blockade of B7-H4 reduces the suppressive activity
      mediated by Treg cell-conditioned APCs. Further, APC-derived, rather than Treg
      cell-derived, IL-10 is responsible for APC B7-H4 induction. Therefore, Treg cells
      convey suppressive activity to APCs by stimulating B7-H4 expression through IL
      10. Altogether, our data provide a novel cellular and molecular mechanism for
      Treg cell-mediated immunosuppression at the level of APCs, and suggest a
      plausible mechanism for the suppressive effect of IL-10 in Treg cell-mediated
      suppression.

PMID- 16785497
TI  - B cells and dendritic cells from V kappa 8 light chain transgenic mice activate
      MRL-lpr/gld CD4+ T cells.
AB  - Autoreactive CD4+ T cells are required for full expression of disease in human
      systemic lupus erythematosus and in spontaneous murine lupus. However, the Ag
      specificity of these CD4+ T cells remains largely unknown. Rheumatoid factor (RF)
      B cells function as highly efficient APCs by taking up immune complexes (IC) and
      presenting IC constituents to T cells. We hypothesized that Ag-specific CD4+ T
      cells in lupus-prone mice could be identified by stimulating the CD4+ T cells
      with RF B cells from AM14 RF BCR transgenic mice pulsed with IC containing lupus
      associated autoantibodies and autoantigens. This approach identified several
      independent T cell lines that proliferated robustly in response to IC-pulsed
      spleen cells from the AM14 RF BCR transgenic mice. However, these T cells did not
      recognize an IC constituent. Instead, these T cells recognized a determinant
      dependent on the inheritance of the transgene-encoded Vkappa8 L chain, most
      likely a neoantigen created by the insertion of the transgene into the genome.
      Additionally, although the precise nature of the neoantigen is not known, the T
      cells described in this report may provide a useful tool for examining the role
      of T cells in the RF autoantibody response.

PMID- 16785498
TI  - Tolerance to proinsulin-2 is due to radioresistant thymic cells.
AB  - Proinsulin is a key Ag in type 1 diabetes, but the mechanisms regulating
      proinsulin immune tolerance are unknown. We have shown that preproinsulin-2 gene
      deficient mice (proins-2(-/-)) are intolerant to proinsulin-2. In this study, we
      analyzed the mechanisms underlying T cell-mediated tolerance to proinsulin-2 in
      129/Sv nonautoimmune mice. The expression of one proinsulin-2 allele, whatever
      its parental origin, was sufficient to maintain tolerance. The site of proinsulin
      2 expression relevant to tolerance was evaluated in thymus and bone marrow
      chimeras. CD4+ T cell reactivity to proinsulin-2 was independent of proinsulin-2
      expression in radiation-sensitive bone marrow-derived cells. A wt thymus restored
      tolerance in proins-2(-/-) mice. Conversely, the absence of the preproinsulin-2
      gene in radioresistant thymic cells was sufficient to break tolerance. Although
      chimeric animals had proinsulin-2-reactive CD4+ T cells in their peripheral
      repertoire, they displayed no insulitis or insulin Abs, suggesting additional
      protective mechanisms. In a model involving transfer to immunodeficient
      (CD3epsilon(-/-)) mice, naive and proinsulin-2-primed CD4+ T cells were not
      activated, but could be activated by immunization regardless of whether the
      recipient mice expressed proinsulin-2. Furthermore, we could not identify a role
      for putative specific T cells regulating proinsulin-2-reactive CD4+ T in transfer
      experiments. Thus, proinsulin-2 gene expression by radioresistant thymic
      epithelial cells is involved in the induction of self-tolerance, and additional
      factors are required to induce islet abnormalities.

PMID- 16785499
TI  - Head kidney-derived macrophages of common carp (Cyprinus carpio L.) show
      plasticity and functional polarization upon differential stimulation.
AB  - Cells from the myeloid lineage are pluripotent. To investigate the potential of
      myeloid cell polarization in a primitive vertebrate species, we phenotypically
      and functionally characterized myeloid cells of common carp (Cyprinus carpio L.)
      during culture. Flow cytometric analysis, Ab labeling of cell surface markers,
      and light microscopy showed the presence of a major population of heterogeneous
      macrophages after culture. These head kidney-derived macrophages can be
      considered the fish equivalent of bone marrow-derived macrophages and show the
      ability to phagocytose, produce radicals, and polarize into innate activated or
      alternatively activated macrophages. Macrophage polarization was based on
      differential activity of inducible NO synthase and arginase for innate and
      alternative activation, respectively. Correspondingly, gene expression profiling
      after stimulation with LPS or cAMP showed differential expression for most of the
      immune genes presently described for carp. The recently described novel Ig-like
      transcript 1 (NILT1) and the CXCR1 and CXCR2 chemokine receptors were up
      regulated after stimulation with cAMP, an inducer of alternative activation in
      carp macrophages. Up-regulation of NILT1 was also seen during the later phase of
      a Trypanosoma carassii infection, where macrophages are primarily alternatively
      activated. However, NILT1 could not be up-regulated during a Trypanoplasma
      borreli infection, a model for innate activation. Our data suggest that NILT1,
      CXCR1, and CXCR2 could be considered markers for alternatively activated
      macrophages in fish.

PMID- 16785500
TI  - ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in
      dendritic cells and macrophages.
AB  - The CIITA is a master regulator for MHC class II expression, but the signaling
      events that control CIITA expression remain poorly understood. In this study, we
      report that both constitutive and IFN-gamma-inducible expression of CIITA in
      mouse bone marrow-derived dendritic cells (DC) and macrophages, respectively, are
      regulated by MAPK signals. In DC, the inhibitory effect of LPS on CIITA
      expression was prevented by MyD88 deficiency or pharmacological MAPK inhibitors
      specific for MEK (U0126) and p38 (SB203580), but not JNK (SP600125). In
      macrophages, LPS inhibited IFN-gamma-inducible CIITA and MHC class II expression
      without affecting expression of IFN regulatory factor-1 and MHC class I. Blocking
      ERK and p38 by MAPK inhibitors not only rescued LPS-mediated inhibition, but also
      augmented IFN-gamma induction of CIITA. Moreover, the induction of CIITA by IFN
      gamma was enhanced by overexpressing MAPK phosphatase-1 that inactivates MAPK.
      Conversely, CIITA expression was attenuated in the absence of MAPK phosphatase-1.
      The down-regulation of CIITA gene expression by ERK and p38 was at least partly
      due to decreased histone acetylation of the CIITA promoter. Our study indicates
      that both MAPK and phosphatase play an important role for CIITA regulation in DC
      and macrophages.

PMID- 16785501
TI  - CD48 is an allergen and IL-3-induced activation molecule on eosinophils.
AB  - Eosinophils are involved in a variety of allergic, parasitic, malignant, and
      idiopathic disorders by releasing a variety of factors including specific granule
      proteins, lipid mediators, and proinflammatory and immunoregulatory cytokines and
      chemokines. In addition, they interact with various cell types in the inflamed
      tissue. Yet, the mechanism of eosinophil activation is still poorly understood.
      Recently, we described the expression and function of the CD2-subfamily of
      receptors and especially 2B4 on human eosinophils. In this study we focus on
      CD48, the high-affinity ligand of 2B4. CD48 is a GPI-anchored protein involved in
      cellular activation, costimulation, and adhesion, but has not been studied on
      eosinophils. We demonstrate that human eosinophils from atopic asthmatics display
      enhanced levels of CD48 expression and that IL-3 up-regulates CD48 expression.
      Furthermore, cross-linking CD48 on human eosinophils triggers release of
      eosinophil granule proteins. Assessment of CD48 expression in a murine model of
      experimental asthma revealed that CD48 is induced by allergen challenge and
      partially regulated by IL-3. Additionally, anti-IL-3 reduces CD48 expression and
      the degree of airway inflammation. Thus, CD48 is an IL-3-induced activating
      receptor on eosinophils, likely involved in promoting allergic inflammation.

PMID- 16785502
TI  - IL-2 immunotoxin therapy modulates tumor-associated regulatory T cells and leads
      to lasting immune-mediated rejection of breast cancers in neu-transgenic mice.
AB  - Studies in cancer patients have suggested that breast tumors recruit regulatory T
      cells (Tregs) into the tumor microenvironment. The extent to which local Tregs
      suppress antitumor immunity in breast cancer is unknown. We questioned whether
      inhibiting systemic Tregs with an IL-2 immunotoxin in a model of neu-mediated
      breast cancer, the neu-transgenic mouse, could impact disease progression and
      survival. As in human breast cancer, cancers that develop in these mice attract
      Tregs into the tumor microenvironment to levels of approximately 10-25% of the
      total CD4+ T cells. To examine the role of Tregs in blocking immune-mediated
      rejection of tumor, we depleted CD4+CD25+ T cells with an IL-2 immunotoxin. The
      treatment depleted Tregs without concomitant lymphopenia and markedly inhibited
      tumor growth. Depletion of Tregs resulted in a persistent antitumor response that
      was maintained over a month after the last treatment. The clinical response was
      immune-mediated because adoptive transfer of Tregs led to a complete abrogation
      of the therapeutic effects of immunotoxin treatment. Further, Treg down
      modulation was accompanied by increased Ag-specific immunity against the neu
      protein, a self Ag. These results suggest that Tregs play a major role in
      preventing an effective endogenous immune response against breast cancer and that
      depletion of Tregs, without any additional immunotherapy, may mediate a
      significant antitumor response.

PMID- 16785503
TI  - Injury-induced suppression of effector T cell immunity requires CD1d-positive
      APCs and CD1d-restricted NKT cells.
AB  - Overwhelming infection remains the leading cause of death from serious burn
      injury despite recent advances in the care of burn patients and a better
      understanding of immune and inflammatory consequences of injury. In this study,
      we report a critical requirement for CD1d-restricted NKT cells and CD1d
      expression by APCs in the immune dysfunction that occurs early after burn injury.
      Using a well-established murine scald injury model with BALB/c and BALB/c CD1d
      knockout mice, we investigated whether peripheral T cell immunity was affected by
      the presence or absence of CD1d-restricted NKT cells in the early stages after
      injury. Using Ag-specific delayed-type hypersensitivity, T cell proliferation,
      and cytokine production as indices of immune responsiveness, we observed that
      both CD1d expression by APCs and CD1d-restricted NKT cells are required for
      immune suppression after injury. Via adoptive transfer of splenocytes from
      injured mice to uninjured recipients, we found injury-induced suppression of
      immunity to be Ag specific, long lasting, and critically dependent on cell
      surface expression of CD1d by APCs. Together, our results suggest that the
      defects in T cell responsiveness that occur subsequent to severe burn injury are
      not merely the result of global or passive suppression, but instead represent an
      active form of CD1d/NKT cell-dependent immunologic tolerance.

PMID- 16785504
TI  - Differential effects of IL-15 and IL-21 in myeloid (CD11b+) and lymphoid (CD11b-)
      bone marrow cells.
AB  - IL-15 has been found to activate NF-kappaB in various types of cells. However,
      the role of this transcription factor in IL-15- and IL-21-stimulated murine bone
      marrow (BM) cells is unclear. In this study, we demonstrated that both IL-15 and
      IL-21 are capable of delaying BM cell factor deprivation-induced apoptosis, but
      only IL-15 induced their proliferation. Following separation of BM cells into
      myeloid (CD11b(+)) and lymphoid (CD11b(-)) cell populations, we found that IL-15,
      but not IL-21, significantly induced proliferation in both cell populations. Both
      cytokines significantly delayed apoptosis, but only in CD11b(-) BM cells. IL
      15Ralpha, CD122 (IL-2/15Rbeta), and common gamma-chains (CD132) were expressed in
      both populations, whereas IL-21Ralpha was expressed only in CD11b(-) BM cells. In
      addition, we demonstrated that IL-15-induced BM cell proliferation was
      significantly inhibited in NF-kappaBp50(-/-) mice when compared with littermate
      controls. The ability of IL-15 and IL-21 to delay BM cell apoptosis was slightly
      inhibited in NF-kappaBp50(-/-) mice, whereas the antiapoptotic effect of LPS was
      markedly reversed. We conclude that IL-15, but not IL-21, induces BM cell
      proliferation and that both cytokines delay BM cell apoptosis. These biological
      activities were preferentially observed in CD11b(-) BM cells. Using NF-kappaBp50(
      /-) mice, we demonstrated for the first time that NF-kappaB plays a greater role
      in IL-15-induced cell proliferation than in IL-15- and IL-21-induced suppression
      of apoptosis.

PMID- 16785505
TI  - The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T
      cells and enhances the generation of T cell precursors.
AB  - The basic helix-loop-helix (bHLH) transcription factors HEB and E2A are critical
      mediators of gene regulation during lymphocyte development. We have cloned a new
      transcription factor, called HEBAlt, from a pro-T cell cDNA library. HEBAlt is
      generated by alternative transcriptional initiation and splicing from the HEB
      gene locus, which also encodes the previously characterized E box protein HEBCan.
      HEBAlt contains a unique N-terminal coding exon (the Alt domain) that replaces
      the first transactivation domain of HEBCan. Downstream of the Alt domain, HEBAlt
      is identical to HEBCan, including the DNA binding domain. HEBAlt is induced in
      early thymocyte precursors and down-regulated permanently at the double negative
      to double positive (DP) transition, whereas HEBCan mRNA expression peaks at the
      DP stage of thymocyte development. HEBAlt mRNA is up-regulated synergistically by
      a combination of HEBCan activity and Delta-Notch signaling. Retroviral
      transduction of HEBAlt or HEBCan into hemopoietic stem cells followed by OP9-DL1
      coculture revealed that HEBAlt-transduced precursors generated more early T
      lineage precursors and more DP pre-T cells than control transduced cells. By
      contrast, HEBCan-transduced cells that maintained high level expression of the
      HEBCan transgene were inhibited in expansion and progression through T cell
      development. HEB(-/-) fetal liver precursors transduced with HEBAlt were rescued
      from delayed T cell specification, but HEBCan-transduced HEB(-/-) precursors were
      not. Therefore, HEBAlt and HEBCan are functionally distinct transcription
      factors, and HEBAlt is specifically required for the efficient generation of
      early T cell precursors.

PMID- 16785506
TI  - Interleukin-21 enhances NK cell activation in response to antibody-coated
      targets.
AB  - NK cells express an activating FcR (FcgammaRIIIa) that mediates Ab-dependent
      cellular cytotoxicity and the production of immune modulatory cytokines in
      response to Ab-coated targets. IL-21 has antitumor activity in murine models that
      depends in part on its ability to promote NK cell cytotoxicity and IFN-gamma
      secretion. We hypothesized that the NK cell response to FcR stimulation would be
      enhanced by the administration of IL-21. Human NK cells cultured with IL-21 and
      immobilized IgG or human breast cancer cells coated with a therapeutic mAb
      (trastuzumab) secreted large amounts of IFN-gamma. Increased secretion of TNF
      alpha and the chemokines IL-8, MIP-1alpha, and RANTES was also observed under
      these conditions. NK cell IFN-gamma production was dependent on distinct signals
      mediated by the IL-21R and the FcR and was abrogated in STAT1-deficient NK cells.
      Supernatants derived from NK cells that had been stimulated with IL-21 and mAb
      coated breast cancer cells were able to drive the migration of naive and
      activated T cells in an in vitro chemotaxis assay. IL-21 also enhanced NK cell
      lytic activity against Ab-coated tumor cells. Coadministration of IL-21 and Ab
      coated tumor cells to immunocompetent mice led to synergistic production of IFN
      gamma by NK cells. Furthermore, the administration of IL-21 augmented the effects
      of an anti-HER2/neu mAb in a murine tumor model, an effect that required IFN
      gamma. These findings demonstrate that IL-21 significantly enhances the NK cell
      response to Ab-coated targets and suggest that IL-21 would be an effective
      adjuvant to administer in combination with therapeutic mAbs.

PMID- 16785507
TI  - Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the
      absence of functional IDO.
AB  - Dendritic cell (DC) tryptophan catabolism has emerged in recent years as a major
      mechanism of peripheral tolerance. However, there are features of this mechanism,
      initiated by IDO, that are still unclear, including the role of enzymes that are
      downstream of IDO in the kynurenine pathway and the role of the associated
      production of kynurenines. In this study, we provide evidence that 1) murine DCs
      express all enzymes necessary for synthesis of the downstream product of
      tryptophan breakdown, quinolinate; 2) IFN-gamma enhances transcriptional
      expression of all of these enzymes, although posttranslational inactivation of
      IDO may prevent metabolic steps that are subsequent and consequent to IDO; 3)
      overcoming the IDO-dependent blockade by provision of a downstream quinolinate
      precursor activates the pathway and leads to the onset of suppressive properties;
      and 4) tolerogenic DCs can confer suppressive ability on otherwise immunogenic
      DCs across a Transwell in an IDO-dependent fashion. Altogether, these data
      indicate that kynurenine pathway enzymes downstream of IDO can initiate
      tolerogenesis by DCs independently of tryptophan deprivation. The paracrine
      production of kynurenines might be one mechanism used by IDO-competent cells to
      convert DCs lacking functional IDO to a tolerogenic phenotype within an IFN-gamma
      rich environment.

PMID- 16785509
TI  - Flotillin-1 regulates IgE receptor-mediated signaling in rat basophilic leukemia
      (RBL-2H3) cells.
AB  - Cross-linking of high-affinity IgE receptors by multivalent Ag on mast cells (rat
      basophilic leukemia (RBL)-2H3) induces the phosphorylation of ITAM motifs of an
      IgE receptor by Src family tyrosine kinase, Lyn. The phosphorylation of IgE
      receptors is followed by a series of intracellular signals, such as Ca(2+)
      mobilization, MAPK activation, and degranulation. Therefore, Lyn is a key
      molecule in the activation of mast cells, but the molecular mechanisms for the
      activation of Lyn are still unclear. Recently, it is suggested that the
      localization of Lyn in lipid rafts is critical for its activation in several cell
      lines, although the precise mechanism is still unknown. In this study, we found
      that flotillin-1, which is localized in lipid rafts, is involved in the process
      of Lyn activation. We obtained flotillin-1 knockdown (KD)(2) rat basophilic
      leukemia (RBL)-2H3 cells, which express a low level of flotillin-1. In the
      flotillin-1 KD cells, we observed a significant decrease in Ca(2+) mobilization,
      the phosphorylation of ERKs, tyrosine phosphorylation of the gamma-subunit of IgE
      receptor, and IgE receptor-mediated degranulation. We also found that flotillin-1
      is constitutively associated with Lyn in lipid rafts in RBL-2H3 cells, and Ag
      stimulation induced the augmentation of flotillin-1 binding to Lyn, resulting in
      enhancement of kinase activity of Lyn. These results suggest that flotillin-1 is
      an essential molecule in IgE receptor-mediated mast cell activation, and
      regulates the kinase activity of Lyn in lipid rafts.

PMID- 16785508
TI  - Self-antigen maintains the innate antibacterial function of self-specific CD8 T
      cells in vivo.
AB  - Self-specific CD8 T cells, which are selected by high-affinity interactions with
      self-Ags, develop into a lineage distinct from conventional CD8 T cells. We have
      previously shown that these self-specific cells acquire phenotypic and functional
      similarities to cells of the innate immune system including the expression of
      functional receptors associated with NK cells. In this study, we show that these
      self-specific cells have the ability to produce large amounts of IFN-gamma in
      response to infection with Listeria monocytogenes in a bystander fashion. The
      rapid production of IFN-gamma is associated with a dramatic reduction in the
      number of viable bacteria at the peak of infection. Self-specific CD8 T cells
      provide only marginal innate protection in the absence of self-Ag; however, the
      presence of self-Ag dramatically increases their protective ability. Exposure to
      self-Ag is necessary for the maintenance of the memory phenotype and
      responsiveness to inflammatory cytokines such as IL-15. Significantly, self
      specific CD8 T cells are also more efficient in the production of IFN-gamma and
      TNF-alpha, thus providing more cytokine-dependent protection against bacterial
      infection when compared with NK cells. These findings illustrate that self
      reactive CD8 T cells can play an important innate function in the early defense
      against bacterial infection.

PMID- 16785510
TI  - A modified tyrosinase-related protein 2 epitope generates high-affinity tumor
      specific T cells but does not mediate therapeutic efficacy in an intradermal
      tumor model.
AB  - The generation of tumor-specific T cells is hampered by the presentation of
      poorly immunogenic tumor-specific epitopes by the tumor. Here, we demonstrate
      that, although CD8+ T cells specific for the self/tumor Ag tyrosinase-related
      protein 2 (TRP2) are readily detected in tumor-bearing hosts, vaccination of
      either tumor-bearing or naive mice with an epitope derived from TRP2 fails to
      generate significant numbers of tetramer-staining TRP2-specific T cells or
      antitumor immunity. We identified an altered peptide epitope, called deltaV,
      which elicits T cell responses that are cross-reactive to the wild-type TRP2
      epitope. Immunization with deltaV generates T cells with increased affinity for
      TRP2 compared with immunization with the wild-type TRP2 epitope, although TRP2
      immunization often generates a greater number of TRP2-specific T cells based on
      intracellular IFN-gamma analysis. Despite generating higher affinity responses,
      deltaV immunization alone fails to provide any greater therapeutic efficacy
      against tumor growth than TRP2 immunization. This lack of tumor protection is
      most likely a result of both the deletion of high affinity and functional
      tolerance induction of lower affinity TRP2-specific T cells. Our data contribute
      to a growing literature demonstrating the ability of variant peptide epitopes to
      generate higher affinity T cell responses against tumor-specific Ags. However,
      consistent with most clinical data, simple generation of higher affinity T cells
      is insufficient to mediate tumor immunity.

PMID- 16785511
TI  - Tumor escape mutants develop within an immune-privileged environment in the
      absence of T cell selection.
AB  - The establishment of tumor escape mutants, which can be driven by innate and/or
      adaptive immune effector cells, presents a significant obstacle in the
      development of successful tumor immunotherapies. Our study documents that tumors
      growing within an immune-privileged site within the eye develop a tumor escape
      phenotype in the absence of selective T cell pressure. P815 tumor cells that are
      recovered from progressively growing tumors within the anterior chamber of the
      eye escape elimination when injected into the flanks of a second group of
      syngeneic DBA/2 mice that were previously immunized against P815 tumor cells. The
      escape phenotype of eye-derived P815 tumors was stable and permanent when the
      tumor cells were cultured in vitro. Eye-derived tumor cells recovered from the
      anterior chamber of CB-17 SCID mice also escaped elimination when injected into
      the flanks of immunized mice, demonstrating that selective pressure by tumor Ag
      specific T cells did not contribute to the development of the escape phenotype.
      In vitro studies demonstrated that eye-derived tumor cells were not lysed by
      specific CTL and were unable to restimulate primed Ag-specific T cells. Immune
      escape of eye-derived tumor cells was not due to down-regulation of either MHC
      class I or ICAM-1. Our data demonstrate that the immune-privileged environment
      within the eye induces a tumor escape phenotype that is not driven by selective T
      cell pressure. We predict that immune escape within the eye is driven by the
      unique ocular environment that permanently alters gene expression in eye-derived
      tumor cells.

PMID- 16785512
TI  - Leptin selectively augments thymopoiesis in leptin deficiency and
      lipopolysaccharide-induced thymic atrophy.
AB  - The thymus is a lymphoid organ that selects T cells for release to the peripheral
      immune system. Unfortunately, thymopoiesis is highly susceptible to damage by
      physiologic stressors and can contribute to immune deficiencies that occur in a
      variety of clinical settings. No treatment is currently available to protect the
      thymus from stress-induced involution. Leptin-deficient (ob/ob) mice have severe
      thymic atrophy and this finding suggests that this hormone is required for normal
      thymopoiesis. In this study, the ability of leptin to promote thymopoiesis in
      wild-type C57BL/6 and BALB/c mice, as well as in leptin-deficient (ob/ob) and
      endotoxin-stressed (Escherichia coli LPS) mice, was determined. Leptin
      administration induced weight loss and stimulated thymopoiesis in ob/ob mice, but
      did not stimulate thymopoiesis in wild-type C57BL/6 nor BALB/c mice. In endotoxin
      stressed mice, however, leptin prevented LPS-induced thymus weight loss and
      stimulated TCRalpha gene rearrangement. Coadministration of leptin with LPS
      blunted endotoxin-induced systemic corticosterone response and production of
      proinflammatory cytokines. Thus, leptin has a selective thymostimulatory role in
      settings of leptin deficiency and endotoxin administration, and may be useful for
      protecting the thymus from damage and augmenting T cell reconstitution in these
      clinical states.

PMID- 16785514
TI  - Indexation as a novel mechanism of lymphocyte homeostasis: the number of
      CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cells.
AB  - To fulfill its mission, the immune system must maintain a complete set of
      different cellular subpopulations that play specific roles in immune responses.
      We have investigated the mechanisms regulating CD4+CD25+ regulatory T (Treg) cell
      homeostasis. We show that the expression of the high-affinity IL-2Ralpha endows
      these cells with the capacity to explore the IL-2 resource, ensuring their
      presence while keeping their number tied to the number of CD4+ T cells that
      produce IL-2. We show that such a homeostatic mechanism allows the increased
      expansion of T cells without causing disease. The indexing of Treg cells to the
      number of activated IL-2-producing cells may constitute a feedback mechanism that
      controls T cell expansion during immune responses, thus preventing autoimmune or
      lymphoproliferative diseases. The present study highlights that maintenance of
      proportions between different lymphocyte subsets may also be critical for the
      immune system and are under strict homeostatic control.

PMID- 16785515
TI  - Prolonged cell cycle transit is a defining and developmentally conserved
      hemopoietic stem cell property.
AB  - Adult mouse hemopoietic stem cells (HSCs) are typically quiescent and enter and
      progress through the cell cycle rarely in steady-state bone marrow, but their
      rate of proliferation can be dramatically enhanced on demand. We have studied the
      cell cycle kinetics of HSCs in the developing fetal liver at a stage when they
      expand extensively. Despite that 100% of fetal liver HSCs divide within a 48-h
      period, their average cell cycle transit time (10.6 h) is twice that of their
      downstream progenitors, translating into a prolonged G(1) transit and a period of
      relative quiescence (G(0)). In agreement with their prolonged G(1) transit when
      compared with hemopoietic progenitors, competitive transplantation experiments
      demonstrate that fetal HSCs are highly enriched in G(1) but also functional in S
      G(2)-M. This observation combined with experimental data demonstrating that adult
      HSCs forced to expand ex vivo also sustain a uniquely prolonged cell cycle and
      G(1) transit, demonstrate at least in part why purified HSCs at any state of
      development or condition are highly enriched in the G(0)-G(1) phases of the cell
      cycle. We propose that a uniquely prolonged cell cycle transit is a defining stem
      cell property, likely to be critical for their maintenance and self-renewal
      throughout development.

PMID- 16785516
TI  - G protein-coupled receptor 83 overexpression in naive CD4+CD25- T cells leads to
      the induction of Foxp3+ regulatory T cells in vivo.
AB  - Foxp3 functions as a lineage specification factor for the development of
      naturally occurring thymus-derived CD4+CD25+ regulatory T (Treg) cells. Recent
      evidence suggests that naive Foxp3-CD4+CD25- T cells can be converted in the
      periphery into Foxp3+ Treg cells. In this study, we have identified the G protein
      coupled receptor (GPR)83 to be selectively up-regulated by CD4+CD25+ Treg cells
      of both murine and human origin in contrast to naive CD4+CD25- or recently
      activated T cells. Furthermore, GPR83 was induced upon overexpression of Foxp3 in
      naive CD4+CD25- T cells. Transduction of naive CD4+CD25- T cells with GPR83
      encoding retroviruses did not confer in vitro suppressive activity. Nevertheless,
      GPR83-transduced T cells were able to inhibit the effector phase of a severe
      contact hypersensitivity reaction of the skin, indicating that GPR83 itself or
      GPR83-mediated signals conferred suppressive activity to conventional CD4+ T
      cells in vivo. Most strikingly, this in vivo acquisition of suppressive activity
      was associated with the induction of Foxp3 expression in GPR83-transduced CD4+ T
      cells under inflammatory conditions. Our results suggest that GPR83 might be
      critically involved in the peripheral generation of Foxp3+ Treg cells in vivo.

PMID- 16785513
TI  - Increased level and longevity of protective immune responses induced by DNA
      vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15
      gene delivery.
AB  - We investigated the ability of a plasmid-derived IL-21 delivered alone or in
      combination with the IL-15 gene to regulate immune responses to the HIV-1
      envelope (Env) glycoprotein induced by DNA vaccination. Mice were injected with
      the gp140DeltaCFI(HXB2/89.6) vector expressing a modified Env glycoprotein with C
      terminal mutations intended to mimic a fusion intermediate, in which the most
      divergent region encoding the variable V1, V2, and V3 domains of CXCR4-tropic
      HxB2 virus was replaced with the dual-tropic 89.6 viral strain. Using a
      recombinant vaccinia virus expressing 89.6 Env glycoprotein (vBD3) in a mouse
      challenge model, we observed that IL-21 plasmid produced sustained resistance to
      viral transmission when injected 5 days after DNA vaccination. Moreover, IL-21 in
      a synergistic manner with IL-15 expression vector augmented the vaccine-induced
      recall responses to the vBD3 challenge compared with those elicited by
      immunization in the presence of either cytokine alone. The synergistic
      combination of IL-21 and IL-15 plasmids promoted expansion of CD8+CD127+ memory T
      cell pools specific for a subdominant HLA-A2-restricted Env(121-129) epitope
      (KLTPLCVTL). Our results also show that coimmunization with IL-21 and IL-15
      plasmid combination resulted in enhanced CD8+ T cell function that was partially
      independent of CD4+ T cell help in mediating protection against vBD3 challenge.
      Furthermore, the use of IL-21 and IL-15 genes was able to increase Ab-dependent
      cellular cytotoxicity and complement-dependent lysis of Env-expressing target
      cells through augmentation of Env-specific IgG Ab levels. These data indicate
      that the plasmid-delivered IL-21 and IL-15 can increase the magnitude of the
      response to DNA vaccines.

PMID- 16785517
TI  - Galectin-1-matured human monocyte-derived dendritic cells have enhanced migration
      through extracellular matrix.
AB  - Dendritic cells (DCs) are potent mediators of the immune response, and can be
      activated by exogenous pathogen components. Galectin-1 is a member of the
      conserved beta-galactoside-binding lectin family that binds galactoside residues
      on cell surface glycoconjugates. Galectin-1 is known to play a role in immune
      regulation via action on multiple immune cells. However, its effects on human DCs
      are unknown. In this study, we show that galectin-1 induces a phenotypic and
      functional maturation in human monocyte-derived DCs (MDDCs) similar to but
      distinct from the activity of the exogenous pathogen stimuli, LPS. Immature human
      MDDCs exposed to galectin-1 up-regulated cell surface markers characteristic of
      DC maturation (CD40, CD83, CD86, and HLA-DR), secreted high levels of IL-6 and
      TNF-alpha, stimulated T cell proliferation, and showed reduced endocytic
      capacity, similar to LPS-matured MDDCs. However, unlike LPS-matured DCs, galectin
      1-treated MDDCs did not produce the Th1-polarizing cytokine IL-12. Microarray
      analysis revealed that in addition to modulating many of the same DC maturation
      genes as LPS, galectin-1 also uniquely up-regulated a significant subset of genes
      related to cell migration through the extracellular matrix (ECM). Indeed,
      compared with LPS, galectin-1-treated human MDDCs exhibited significantly better
      chemotactic migration through Matrigel, an in vitro ECM model. Our findings show
      that galectin-1 is a novel endogenous activator of human MDDCs that up-regulates
      a significant subset of genes distinct from those regulated by a model exogenous
      stimulus (LPS). One unique effect of galectin-1 is to increase DC migration
      through the ECM, suggesting that galectin-1 may be an important component in
      initiating an immune response.

PMID- 16785518
TI  - Tight linkage between translation and MHC class I peptide ligand generation
      implies specialized antigen processing for defective ribosomal products.
AB  - There is mounting evidence that MHC class I peptide ligands are predominantly
      generated from defective ribosomal products and other classes of polypeptides
      degraded rapidly (t1/2 < 10 min) following their synthesis. The most direct
      evidence supporting this conclusion is the rapid inhibition of peptide ligand
      generation following cycloheximide-mediated inhibition of protein synthesis. In
      this study, we show that this linkage is due to depleting the pool of rapidly
      degraded proteins, and not to interference with other protein synthesis-dependent
      processes. Our findings indicate that in the model systems used in this study,
      MHC class I peptides are preferentially generated from rapidly degraded
      polypeptides relative to slowly degraded proteins. This conclusion is supported
      by the properties of peptide presentation from slowly degraded (t1/2 = 4 h)
      defective ribosomal products generated artificially by incorporation of the amino
      acid analog canavanine into a model viral Ag. We propose that specialized
      machinery exists to link protein synthesis with class I peptide ligand generation
      to enable the rapid detection of viral gene expression.

PMID- 16785519
TI  - IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134
      pathway.
AB  - IL-18 induces inflammation resulting in either enhanced protection from pathogens
      or exacerbation of autoimmunity, and T cells are profoundly activated during
      these responses. How IL-18 influences T cell activation is unknown, but this
      study in mice shows that IL-18 boosted Ag-specific T cell clonal expansion of
      effector T cells and induced a subpopulation of IFN-gamma superproducing T cells.
      Commitment to IFN-gamma production through IL-18 was independent of NK cells and
      IL-12 but dependent on host-derived IFN-gamma. To determine how expansion of
      these effectors occurred, IL-18 was shown to induce OX40L on dendritic cells,
      whereas peptide stimulation induced CD134 (OX40) on specific T cells. CD134
      blockade inhibited T cell effector expansion thereby reducing the number of IFN
      gamma superproducers by 12-fold. Thus, independent of IL-12, IL-18 impacts T cell
      immunity throughout lymphoid and nonlymphoid tissue by bridging the innate and
      adaptive arms of the immune system through IFN-gamma and the CD134 costimulatory
      pathway.

PMID- 16785520
TI  - FOXP3+CD4+CD25+ adaptive regulatory T cells express cyclooxygenase-2 and suppress
      effector T cells by a prostaglandin E2-dependent mechanism.
AB  - CD4+CD25+ regulatory T (T(R)) cells suppress effector T cells by partly unknown
      mechanisms. In this study, we describe a population of human suppressive
      CD4+CD25+ adaptive T(R) (T(R)(adapt)) cells induced in vitro that express
      cyclooxygenase 2 (COX-2) and the transcription factor FOXP3. T(R)(adapt) cells
      produce PGE(2) and suppress effector T cell responses in a manner that is
      reversed by COX inhibitors and PGE(2) receptor-specific antagonists. In resting
      CD4+CD25- T cells, treatment with PGE(2) induced FOXP3 expression. Thus,
      autocrine and paracrine effects of PGE(2) produced by COX-2-positive T(R)(adapt)
      cells may be responsible for both the FOXP3+ phenotype and the mechanism used by
      these cells to suppress effector T cells.

PMID- 16785521
TI  - Accumulation of CD8+ T cells in advanced-stage tumors and delay of disease
      progression following secondary immunization against an immunorecessive epitope.
AB  - Self-reactive T cells that survive the process of positive and negative selection
      during thymocyte development represent potential effector cells against tumors
      that express these same self-Ags. We have previously shown that CD8+ T
      lymphocytes (T(CD8)) specific for an immunorecessive epitope, designated epitope
      V, from the SV40 large T Ag (Tag) escape thymic deletion in line SV11 Tag
      transgenic mice. In contrast, these mice are tolerant to the three most dominant
      Tag epitopes. The majority of the residual epitope V-specific T(CD8) have a low
      avidity for the target epitope, but a prime/boost regimen can expand higher
      avidity clones in vivo. Whether higher avidity T(CD8) targeting this epitope are
      affected by Tag-expressing tumors in the periphery or can be recruited for
      control of tumor progression remains unknown. In the current study, we determined
      the fate of naive TCR-transgenic T(CD8) specific for Tag epitope V (TCR-V cells)
      following transfer into SV11 mice bearing advanced-stage choroid plexus tumors.
      The results indicate that TCR-V cells are rapidly triggered by the endogenous Tag
      and acquire effector function, but fail to accumulate within the tumors. Primary
      immunization enhanced TCR-V cell frequency in the periphery and promoted entry
      into the brain, but a subsequent booster immunization caused a dramatic
      accumulation of TCR-V T cells within the tumors and inhibited tumor progression.
      These results indicate that epitope V provides a target for CD8+ T cells against
      spontaneous tumors in vivo, and suggests that epitopes with similar properties
      can be harnessed for tumor immunotherapy.

PMID- 16785522
TI  - CD44 differentially activates mouse NK T cells and conventional T cells.
AB  - NK T (NKT) cells are an important component of the innate immune system and
      recognize the MHC class I-like CD1d molecule. NKT cells possess significant
      immunoregulatory activity due to their rapid secretion of large quantities of pro
      and anti-inflammatory cytokines following CD1d-dependent stimulation. Because
      the innate immune system is programmed to respond to a multitude of diverse
      stimuli and must be able to quickly differentiate between pathogenic and
      endogenous signals, we hypothesized that, apart from stimulation via the TCR
      (e.g., CD1d-dependent activation), there must be multiple activation pathways
      that can be triggered through other cell surface receptors on NKT cells.
      Therefore, we analyzed the ability of CD44, a structurally diverse cell surface
      receptor expressed on most cells, to stimulate murine NKT cells, compared with
      conventional T cells. Stimulation of CD44 through Ab cross-linking or binding to
      its natural ligands hyaluronan and osteopontin induced NKT cells to secrete
      cytokines, up-regulate activation markers, undergo morphological changes, and
      resist activation-induced cell death, whereas conventional T cells only exhibited
      changes in morphology and protection from activation-induced cell death. This
      CD44-specific stimulation of NKT cells correlated with their ability to bind
      hyaluronan. Thus, fundamental differences in CD44 function between these
      lymphocyte subsets suggest an important biological role for CD44 in the innate
      immune response.

PMID- 16785523
TI  - Follicular dendritic cells are related to bone marrow stromal cell progenitors
      and to myofibroblasts.
AB  - Follicular dendritic cells (FDC) are involved in the presentation of native Ags
      to B cells during the secondary immune response. Some authors consider FDC to be
      hemopoietic cells, whereas others believe them to be mesenchymal cells. The low
      proportion of FDC in the lymphoid follicle, together with technical difficulties
      in their isolation, make these cells difficult to study. We show that Fibroblast
      Medium can be used successfully to isolate and maintain FDC lines. In this
      culture medium, we obtained 18 FDC lines from human tonsils, which proliferated
      for as long as 18 wk and showed a stable Ag phenotype as detected by flow
      cytometry and RT-PCR. FDC lines were CD45-negative and expressed Ags associated
      to FDC (CD21, CD23, CD35, CD40, CD73, BAFF, ICAM-1, and VCAM-1) and Ags specific
      for FDC (DRC-1, CNA.42, and HJ2). These cell lines were also able to bind B cells
      and secrete CXCL13, functional activities characteristic of FDC. Nevertheless,
      the additional expression of STRO-1, together with CD10, CD13, CD29, CD34, CD63,
      CD73, CD90, ICAM-1, VCAM-1, HLA-DR, alkaline phosphatase, and alpha-smooth muscle
      actin (alpha-SM actin) indicated that FDC are closely related to bone marrow
      stromal cell progenitors. The expression of alpha-SM actin also relates FDC with
      myofibroblasts. Like myofibroblasts, FDC lines expressed stress fibers containing
      alpha-SM actin and were able to contract collagen gels under the effect of
      TGFbeta1 and platelet-derived growth factor. These findings suggest that FDC are
      a specialized form of myofibroblast and derive from bone marrow stromal cell
      progenitors.

PMID- 16785524
TI  - Lymphotoxin pathway-directed, autoimmune regulator-independent central tolerance
      to arthritogenic collagen.
AB  - Ectopic expression of peripherally restricted Ags by medullary thymic epithelial
      cells (mTECs) is associated with negative selection. Autoimmune regulator (AIRE)
      is considered to be the master regulator of these Ags. We show in this study that
      the ectopic expression of type II collagen (CII) in mTECs and the corresponding
      central tolerance to CII are AIRE independent but lymphotoxin dependent. The
      failure to properly express CII in mTECs of Lta(-/-) and Ltbr(-/-) mice leads to
      overt autoimmunity to CII and exquisite susceptibility to arthritis. These
      findings define the existence of additional pathways of ectopic peripheral Ag
      expression, parallel to and independent of AIRE, which may cover an extended
      spectrum of peripheral Ags in the thymus.

PMID- 16785525
TI  - TLR activation of Langerhans cell-like dendritic cells triggers an antiviral
      immune response.
AB  - Langerhans cells (LC) are a unique subset of dendritic cells (DC), present in the
      epidermis and serving as the first line of defense against pathogens invading the
      skin. To investigate the role of human LCs in innate immune responses, we
      examined TLR expression and function of LC-like DCs derived from CD34+ progenitor
      cells and compared them to DCs derived from peripheral blood monocytes (monocyte
      derived DC; Mo-DC). LC-like DCs and Mo-DCs expressed TLR1-10 mRNAs at comparable
      levels. Although many of the TLR-induced cytokine patterns were similar between
      the two cell types, stimulation with the TLR3 agonist poly(I:C) triggered
      significantly higher amounts of the IFN-inducible chemokines CXCL9 (monokine
      induced by IFN-gamma) and CXCL11 (IFN-gamma-inducible T cell alpha
      chemoattractant) in LC-like DCs as compared with Mo-DCs. Supernatants from TLR3
      activated LC-like DCs reduced intracellular replication of vesicular stomatitis
      virus in a type I IFN-dependent manner. Finally, CXCL9 colocalized with LCs in
      skin biopsy specimens from viral infections. Together, our data suggest that LCs
      exhibit a direct antiviral activity that is dependent on type I IFN as part of
      the innate immune system.

PMID- 16785526
TI  - IL-2 in vivo activities and antitumor efficacy enhanced by an anti-IL-2 mAb.
AB  - IL-2 is a potent immunostimulant and has been tested for clinical use, including
      in immunotherapy for cancers and HIV infection. Here we show that a widely used
      neutralizing anti-murine IL-2 mAb (S4B6) exhibits unexpected activities that
      enhance the treatment effects of IL-2 in vivo. Coinjection of the anti-IL-2 mAb
      with a plasmid carrying murine IL-2 cDNA significantly increased the serum IL-2
      levels and induced a substantial increase in the division of CD8+ T and
      NK1.1(high) cells in vivo. Injection of the mAb premixed with recombinant murine
      IL-2 showed the same enhanced effect. A 5-day treatment with the anti-IL-2 mAb
      alone gradually increased the CD44(high)CD8+ population, and the increased
      population was maintained for >300 days, suggesting that the mAb can gradually
      maintain and potentially enhance the bioactivity of endogenous IL-2 for extended
      periods. Furthermore, combined treatment with the anti-IL-2 mAb plus the IL-2
      plasmid markedly enhanced Ag-specific CTL activity in vivo and partially
      protected mice from tumor metastasis to the lungs, compared with the anti-IL-2
      mAb or IL-2 plasmid alone. These results demonstrated IL-2-enhancing effects of
      the anti-IL-2 mAb in vivo and suggest that combining a neutralizing anti-IL-2 Ab
      with IL-2 gene delivery might be used effectively to enhance IL-2 functions in
      clinical applications.

PMID- 16785527
TI  - IFN-gamma and its receptor subunit IFNGR1 are recruited to the IFN-gamma
      activated sequence element at the promoter site of IFN-gamma-activated genes:
      evidence of transactivational activity in IFNGR1.
AB  - We have shown previously that IFN-gamma and one of its receptor subunits, IFNGR1,
      are translocated to the nucleus, together with STAT1alpha as one macromolecular
      complex, via the classical importin-dependent pathway. In this study, we have
      identified the nuclear targets of IFN-gamma and IFNGR1. By chromatin
      immunoprecipitation followed by PCR, IFN-gamma, its receptor subunit IFNGR1, and
      STAT1alpha were found to be associated with the IFN-gamma-activated sequence
      (GAS) in the promoter of two of the genes stimulated by IFN-gamma.
      Immunoprecipitated chromatin also showed the association of the IFN-gamma,
      IFNGR1, and STAT1alpha on the same DNA sequence. Examination of nuclear extracts
      from WISH cells treated with IFN-gamma revealed the specific binding of IFN
      gamma, IFNGR1, and STAT1alpha to biotinylated GAS nucleotide sequence.
      Association of IFN-gamma, IFNGR1, and STAT1alpha with the GAS promoter was also
      demonstrated by EMSA. Transfection with a GAS-luciferase gene together with the
      IFNGR1 and nonsecreted IFN-gamma resulted in enhanced reporter activity. In
      addition, IFNGR1 fused to the yeast GAL4 DNA binding domain resulted in enhanced
      transcription from a GAL4 response element, suggesting the presence of a trans
      activation domain in IFNGR1. Our observations put IFN-gamma and its receptor
      subunit, IFNGR1, in direct contact with the promoter region of IFN-gamma
      activated genes with associated increased activity, thus suggesting a
      transcriptional/cotranscriptional role for IFN-gamma/IFNGR1 as well as a possible
      role in determining the specificity of IFN-gamma action.

PMID- 16785528
TI  - Analysis of TLR4 polymorphic variants: new insights into TLR4/MD-2/CD14
      stoichiometry, structure, and signaling.
AB  - TLR4 is the signal-transducing receptor for structurally diverse microbial
      molecules such as bacterial LPS, respiratory syncytial virus fusion (F) protein,
      and chlamydial heat shock protein 60. Previous studies associated two polymorphic
      mutations in the extracellular domain of TLR4 (Asp(299)Gly and Thr(399)Ile) with
      decreased LPS responsiveness. To analyze the molecular basis for diminished
      responsiveness, site-specific mutations (singly or coexpressed) were introduced
      into untagged and epitope (Flag)-tagged wild-type (WT) TLR4 expression vectors to
      permit a direct comparison of WT and mutant signal transduction. Coexpression of
      WT TLR4, CD14, and MD-2 expression vectors in HEK293T cells was first optimized
      to achieve optimal LPS-induced NF-kappaB reporter gene expression. Surprisingly,
      transfection of cells with MD-2 at high input levels often used in the literature
      suppressed LPS-induced signaling, whereas supraoptimal CD14 levels did not. Under
      conditions where WT and polymorphic variants were comparably expressed,
      significant differences in NF-kappaB activation were observed in response to LPS
      and two structurally unrelated TLR4 agonists, chlamydial heat shock protein 60
      and RSV F protein, with the double, cosegregating mutant TLR4 exhibiting the
      greatest deficiency. Overexpression of Flag-tagged WT and mutant vectors at input
      levels resulting in agonist-independent signaling led to equivalent NF-kappaB
      signaling, suggesting that these mutations in TLR4 affect appropriate interaction
      with agonist or coreceptor. These data provide new insights into the importance
      of stoichiometry among the components of the TLR4/MD-2/CD14 complex. A structural
      model that accounts for the diminished responsiveness of mutant TLR4
      polymorphisms to structurally unrelated TLR4 agonists is proposed.

PMID- 16785529
TI  - Trends in antibody sequence changes during the somatic hypermutation process.
AB  - Probable germline gene sequences from thousands of aligned mature Ab sequences
      are inferred using simple computational matching to known V(D)J genes. Comparison
      of the germline to mature sequences in a structural region-dependent fashion
      allows insights into the methods that nature uses to mature Abs during the
      somatic hypermutation process. Four factors determine the residue type mutation
      patterns: biases in the germline, accessibility from single base permutations,
      location of mutation hotspots, and functional pressures during selection.
      Germline repertoires at positions that commonly contact the Ag are biased with
      tyrosine, serine, and tryptophan. These residue types have a high tendency to be
      present in mutation hotspot motifs, and their abundance is decreased during
      maturation by a net conversion to other types. The heavy use of tyrosines on
      mature Ab interfaces is thus a reflection of the germline composition rather than
      being due to selection during maturation. Potentially stabilizing changes such as
      increased proline usage and a small number of double cysteine mutations capable
      of forming disulfide bonds are ascribed to somatic hypermutation. Histidine is
      the only residue type for which usage increases in each of the interface, core,
      and surface regions. The net overall effect is a conversion from residue types
      that could provide nonspecific initial binding into a diversity of types that
      improve affinity and stability. Average mutation probabilities are approximately
      4% for core residues, approximately 5% for surface residues, and approximately
      12% for residues in common Ag-contacting positions, excepting the those coded by
      the D gene.

PMID- 16785530
TI  - Inhibition of MHC class II expression and immune responses by c-MIR.
AB  - We previously reported a novel E3 ubiquitin ligase (E3), designated as c-MIR,
      which targets B7-2 to lysosomal degradation and down-regulates the B7-2 surface
      expression through ubiquitination of its cytoplasmic tail. B7-2 is well known as
      a costimulatory molecule for Ag presentation, suggesting that the manipulation of
      c-MIR expression modulates immune responses in vivo. To examine this hypothesis,
      we generated genetically modified mice in which c-MIR was expressed under an
      invariant chain (Ii) promoter. Dendritic cells derived from genetically
      engineered mice showed low ability to present Ags. In addition, these mice showed
      resistance to the onset of experimental autoimmune encephalomyelitis and an
      impaired development of CD4 T cells in the thymus and the periphery. These
      findings led us to conclude that MHC class II (MHC II) is an additional target
      for c-MIR. Indeed, forced expression of c-MIR in several B cell lines down
      regulated the surface expression of MHC II, and down-regulation was found to
      depend on the presence of a single lysine residue in the cytoplasmic tail of the
      I-A beta-chain. In a reconstitution system using 293T cells, we found that the
      lysine residue at position 225 in the I-A beta-chain was ubiquitinated by c-MIR.
      To our knowledge, c-MIR is the first example of an E3 that is capable of
      inhibiting MHC II expression. Our findings suggest that c-MIR might potently
      regulate immune responses in vivo.

PMID- 16785531
TI  - Structural phylogenetic analysis of activation-induced deaminase function.
AB  - In mammals, activation-induced deaminase (AID) initiates somatic hypermutation
      (SHM) and class switch recombination (CSR) of Ig genes. SHM and CSR activities
      require separate regions within AID. A chromosome region maintenance 1 (CRM1)
      dependent nuclear export signal (NES) at the AID C terminus is necessary for CSR,
      and has been suggested to associate with CSR-specific cofactors. CSR appeared
      late in AID evolution, during the emergence of land vertebrates from bony fish,
      which only display SHM. Here, we show that AID from African clawed frog (Xenopus
      laevis), but not pufferfish (Takifugu rubripes), can induce CSR in AID-deficient
      mouse B cells, although both are catalytically active in bacteria and mammalian
      cell systems, albeit at decreased level. Like mammalian AID, Takifugu AID is
      actively exported from the cell nucleus by CRM1, and the Takifugu NES can
      substitute for the equivalent region in human AID, indicating that all the CSR
      essential NES motif functions evolutionarily predated CSR activity. We also show
      that fusion of the Takifugu AID catalytic domain to the entire human noncatalytic
      domain restores activity in mammalian cells, suggesting that AID features mapping
      within the noncatalytic domain, but outside the NES, influence its function.

PMID- 16785532
TI  - The biological activity of human CD20 monoclonal antibodies is linked to unique
      epitopes on CD20.
AB  - We have previously defined a panel of fully human CD20 mAb. Most of these were
      unexpectedly efficient in their ability to recruit C1q to the surface of CD20
      positive cells and mediate tumor lysis via activation of the classical pathway of
      complement. This complement-dependent cytotoxicity (CDC) potency appeared to
      relate to the unusually slow off-rate of these human Abs. However, we now present
      epitope-mapping data, which indicates that all human mAb bind a novel region of
      CD20 that may influence CDC potency. Epitope mapping, using both mutagenesis
      studies and overlapping 15-mer peptides of the extracellular loops of CD20,
      defined the amino acids required for binding by an extensive panel of mouse and
      human mAb. Binding by rituximab and mouse CD20 mAb, had an absolute requirement
      for alanine and proline at positions 170 and 172, respectively, within the large
      extracellular loop of CD20. Surprisingly, however, all of the human CD20 mAb
      recognize a completely novel epitope located N-terminally of this motif, also
      including the small extracellular loop of CD20. Thus, although off-rate may
      influence biological activity of mAb, another critical factor for determining CDC
      potency by CD20 mAb appears to be the region of the target molecule they
      recognize. We conclude that recognition of the novel epitope cooperates with slow
      off-rate in determining the activity of CD20 Ab in activation of complement and
      induction of tumor cell lysis.

PMID- 16785533
TI  - Signal regulatory protein molecules are differentially expressed by CD8-
      dendritic cells.
AB  - A normalized subtracted gene expression library was generated from freshly
      isolated mouse dendritic cells (DC) of all subtypes, then used to construct cDNA
      microarrays. The gene expression profiles of the three splenic conventional DC
      (cDC) subsets were compared by microarray hybridization and two genes encoding
      signal regulatory protein beta (Sirpbeta1 and Sirpbeta4) molecules were
      identified as differentially expressed in CD8(-) cDC. Genomic sequence analysis
      revealed a third Sirpbeta member localized in the same gene cluster. These
      Sirpbeta genes encode cell surface molecules containing extracellular Ig domains
      and short intracytoplasmic domains that have a charged amino acid in the
      transmembrane region which can potentially interact with ITAM-bearing molecules
      to mediate signaling. Indeed, we demonstrated interactions between Sirpbeta1 and
      beta2 with the ITAM-bearing signaling molecule Dap12. Real-time PCR analysis
      showed that all three Sirpbeta genes were expressed by CD8(-) cDC, but not by
      CD8(+) cDC or plasmacytoid pre-DC. The related Sirpalpha gene showed a similar
      expression profile on cDC subtypes but was also expressed by plasmacytoid pre-DC.
      The differential expression of Sirpalpha and Sirpbeta1 molecules on DC was
      confirmed by staining with mAbs, including a new mAb recognizing Sirpbeta1. Cross
      linking of Sirpbeta1 on DC resulted in a reduction in phagocytosis of Leishmania
      major parasites, but did not affect phagocytosis of latex beads, perhaps
      indicating that the regulation of phagocytosis by Sirpbeta1 is a ligand-dependent
      interaction. Thus, we postulate that the differential expression of these
      molecules may confer the ability to regulate the phagocytosis of particular
      ligands to CD8(-) cDC.

PMID- 16785534
TI  - Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for
      IFN-alpha: a potential role in systemic lupus erythematosus.
AB  - Human complement receptor type 2 (CR2/CD21) is a B lymphocyte membrane
      glycoprotein that plays a central role in the immune responses to foreign Ags as
      well as the development of autoimmunity to nuclear Ags in systemic lupus
      erythematosus. In addition to these three well-characterized ligands, C3d/iC3b,
      EBV-gp350, and CD23, a previous study has identified CR2 as a potential receptor
      for IFN-alpha. IFN-alpha, a multifunctional cytokine important in the innate
      immune system, has recently been proposed to play a major pathogenic role in the
      development of systemic lupus erythematosus in humans and mice. In this study, we
      have shown using surface plasmon resonance and ELISA approaches that CR2 will
      bind IFN-alpha in the same affinity range as the other three well-characterized
      ligands studied in parallel. In addition, we show that IFN-alpha interacts with
      short consensus repeat domains 1 and 2 in a region that serves as the ligand
      binding site for C3d/iC3b, EBV-gp350, and CD23. Finally, we show that treatment
      of purified human peripheral blood B cells with the inhibitory anti-CR2 mAb 171
      diminishes the induction of IFN-alpha-responsive genes. Thus, IFN-alpha
      represents a fourth class of extracellular ligands for CR2 and interacts with the
      same domain as the other three ligands. Defining the role of CR2 as compared with
      the well-characterized type 1 IFN-alpha receptor 1 and 2 in mediating innate
      immune and autoimmune roles of this cytokine should provide additional insights
      into the biologic roles of this interaction.

PMID- 16785535
TI  - E2A expression stimulates Ig hypermutation.
AB  - Ig hypermutation is limited to a region of approximately 2 kb downstream of the
      transcription start sites of the Ig loci. The process requires transcription and
      the presence of Ig enhancer sequences, and is initiated by the activation-induced
      cytidine deaminase (AID)-mediated deamination of cytidine bases. It remains
      unknown why AID causes mutations selectively in the Ig genes and not in most
      other transcribed loci of B cells. In this study, we report that the inactivation
      of the E2A gene strongly reduces the rate of Ig L chain mutations in the chicken
      B cell line DT40 without affecting the levels of surface Ig or AID expression.
      The defect is complemented by the expression of cDNAs corresponding to either of
      the two E2A splice variants E12 or E47. The results suggest that E2A-encoded
      proteins enhance Ig hypermutation by recruitment of AID to the Ig loci.

PMID- 16785536
TI  - p300/Cyclic AMP-responsive element binding-binding protein mediates
      transcriptional coactivation by the CD28 T cell costimulatory receptor.
AB  - During Ag stimulation of T cells, the recognition of B7 molecules by the CD28
      costimulatory receptor increases the level of c-Fos, a component of the AP-1
      transactivator known to bind the 5' Il2 gene enhancer. In this study, we show
      that the costimulation of Fos transcription by CD28 is associated with increased
      binding of p300/CREB-binding protein (CBP) molecules at the Fos promoter, and is
      blocked by an adenoviral E1A molecular antagonist of p300/CBP. Furthermore,
      transcriptional activation by a C-terminal domain of CBP is strengthened when
      CD28 molecules are actively signaling. This increased amount and activity of
      p300/CBP molecules at the Fos gene correlated with higher histone H4 acetylation
      and RNA polymerase II association with the promoter. These data suggest a global
      mechanism whereby CD28 signaling influences the rate and intensity of new gene
      expression during Ag recognition via direct control over the coactivator function
      of p300/CBP.

PMID- 16785537
TI  - A role for DNA hypomethylation and histone acetylation in maintaining allele
      specific expression of mouse NKG2A in developing and mature NK cells.
AB  - The repertoire of receptors that is expressed by NK cells is critical for their
      ability to kill virally infected or transformed cells. However, the molecular
      mechanisms that determine whether and when NK receptor genes are transcribed
      during hemopoiesis remain unclear. In this study, we show that hypomethylation of
      a CpG-rich region in the mouse NKG2A gene is associated with transcription of
      NKG2A in ex vivo NK cells and NK cell lines. This observation was extended to
      various developmental stages of NK cells sorted from bone marrow, in which we
      demonstrate that the CpGs are methylated in the NKG2A-negative stages
      (hemopoietic stem cells, NK progenitors, and NKG2A-negative NK cells), and
      hypomethylated specifically in the NKG2A-positive NK cells. Furthermore, we
      provide evidence that DNA methylation is important in maintaining the allele
      specific expression of NKG2A. Finally, we show that acetylated histones are
      associated with the CpG-rich region in NKG2A positive, but not negative, cell
      lines, and that treatment with the histone deacetylase inhibitor trichostatin A
      alone is sufficient to induce NKG2A expression. Treatment with the
      methyltransferase inhibitor 5-azacytidine only is insufficient to induce
      transcription, but cotreatment with both drugs resulted in a significantly
      greater induction, suggesting a cooperative role for DNA methylation and histone
      acetylation status in regulating gene expression. These results enhance our
      understanding of the formation and maintenance of NK receptor repertoires in
      developing and mature NK cells.

PMID- 16785538
TI  - Mycobacterium tuberculosis LprA is a lipoprotein agonist of TLR2 that regulates
      innate immunity and APC function.
AB  - TLR2 recognizes components of Mycobacterium tuberculosis (Mtb) and initiates
      responses by APCs that influence both innate and adaptive immunity. Mtb
      lipoproteins are an important class of TLR2 ligand, but only two, LpqH and LprG,
      have been characterized to date. In this study, we characterize a third Mtb
      lipoprotein, LprA, and determine its effects on host macrophages and dendritic
      cells. LprA is a cell wall-associated lipoprotein with no homologs outside the
      slow-growing mycobacteria. Using Mycobacterium smegmatis as an expression host,
      we purified 6x His-tagged LprA both with and without its acyl modifications.
      Acylated LprA had agonist activity for both human and murine TLR2 and induced
      expression of TNF-alpha, IL-10, and IL-12. LprA also induced dendritic cell
      maturation as shown by increased expression of CD40, CD80, and class II MHC (MHC
      II). In macrophages, prolonged (24 h) incubation with LprA decreased IFN-gamma
      induced MHC-II Ag processing and presentation, consistent with an observed
      decrease in MHC-II expression (macrophage viability was not affected and
      apoptosis was not induced by LprA). Reduced MHC-II Ag presentation may represent
      a negative feedback mechanism for control of inflammation that may be subverted
      by Mtb for immune evasion. Thus, Mtb LprA is a TLR2 agonist that induces cytokine
      responses and regulates APC function.

PMID- 16785539
TI  - Haemophilus influenzae surface fibrils contribute to serum resistance by
      interacting with vitronectin.
AB  - Vitronectin inhibits the membrane attack complex of the complement system and is
      found both in plasma and the extracellular matrix. In this study, we have
      identified the outer membrane protein Haemophilus surface fibrils (Hsf) as the
      major vitronectin-binding protein in encapsulated H. influenzae type b. A H.
      influenzae mutant devoid of Hsf showed a significantly decreased binding to both
      soluble and immobilized vitronectin as compared with the wild-type counterpart.
      Moreover, Escherichia coli-expressing Hsf at the surface strongly adhered to
      immobilized vitronectin. Importantly, the H. influenzae Hsf mutant had a markedly
      reduced survival as compared with the wild-type bacterium when incubated with
      normal human serum. A series of truncated Hsf fragments were recombinantly
      manufactured in E. coli. The vitronectin binding regions were located within two
      separate binding domains. In conclusion, Hsf interacts with vitronectin and
      thereby inhibits the complement-mediated bactericidal activity, and thus is a
      major H. influenzae virulence factor.

PMID- 16785540
TI  - Secreted proteins from Mycobacterium tuberculosis gain access to the cytosolic
      MHC class-I antigen-processing pathway.
AB  - CD8+ T cells play an important role in the host response to infection with
      Mycobacterium tuberculosis (Mtb). Mtb resides in an arrested phagosome that is
      phenotypically similar to an early endosome. The mechanisms by which Mtb-derived
      Ags gain access to the HLA-I-processing pathway are incompletely characterized.
      Studies with CD8+ T cell lines have suggested that Mtb Ags gain access to the HLA
      I pathway in an alternate vacuolar pathway that is both brefeldin A (BFA) and TAP
      independent. To define the requirements of entry of Ag into the HLA-I pathway, we
      have used human CD8+ T cell clones specific for the secreted Mtb Ag CFP10. Human
      monocyte-derived dendritic cells were pulsed with CFP10 expressed in a
      recombinant adenovirus, surface adsorbed to microspheres, or in its native form
      by Mtb. When delivered by adenovirus, processing and presentation of CFP10 were
      blocked by both BFA and the proteasomal blocker lactacystin. In contrast,
      processing of CFP10 adsorbed to the surface of microspheres was not affected by
      either of these Ag-processing inhibitors. BFA, lactacystin, and TAP inhibition
      blocked the recognition of Mtb-infected dendritic cells, suggesting that
      processing was via a cytosolic pathway for this secreted protein Ag. We conclude
      that secreted proteins from Mtb can be processed in a BFA- and proteasome
      dependent manner, consistent with egress of Ag into the cytosol and subsequent
      loading of proteasomally derived peptides.

PMID- 16785541
TI  - Novel activities of cyclophilin A and cyclosporin A during HIV-1 infection of
      primary lymphocytes and macrophages.
AB  - Studies conducted in cell lines indicate that cyclophilin A (CypA) is a component
      of HIV type 1 (HIV-1) virions, and that when CypA incorporation into virions is
      inhibited by treatment of infected cells with the immunosuppressive agent
      cyclosporin A (CsA), HIV-1 infection also is inhibited. Because HIV-1 particles
      assemble along a different pathway and incorporate different host proteins in
      macrophages than in other cell types, we investigated CypA and CsA activities in
      HIV-1-infected primary human macrophages, compared with primary human
      lymphocytes. We tested virus protein production, virion composition and
      infectivity, and progress through the virus life cycle under perturbation by drug
      treatment or mutagenesis in infected cells from multiple donors. Our findings
      from both primary cell types are different from that previously reported in
      transformed cells and show that the amount of CypA incorporated into virions is
      variable and that CsA inhibits HIV-1 infection at both early and late phases of
      virus replication, the stage affected is determined by the sequence of HIV-1 Gag.
      Because the cell type infected determines the identity of host proteins active in
      HIV-1 replication and can influence the activity of some viral inhibitors,
      infection of transformed cells may not recapitulate infection of the native
      targets of HIV-1.

PMID- 16785542
TI  - Four distinct patterns of memory CD8 T cell responses to chronic murine
      cytomegalovirus infection.
AB  - CMVs are beta herpesviruses that establish lifelong latent infection of their
      hosts. Acute infection of C57BL/6 mice with murine CMV elicits a very broad CD8 T
      cell response, comprising at least 24 epitopes from 18 viral proteins. In
      contrast, we show here that the CD8 T cell response in chronically infected mice
      was dominated by only five epitopes. Altogether, four distinct CD8 T cell kinetic
      patterns were evident. Responses to some epitopes, including M45, which dominates
      the acute response, contracted sharply after day 7 and developed into stable long
      term memory. The response to m139 underwent rapid expansion and contraction,
      followed by a phase of memory inflation, whereas the response to an M38 epitope
      did not display any contraction phase. Finally, responses against two epitopes
      encoded by the immediate early gene IE3 were readily detectable in chronically
      infected mice but near the limit of detection during acute infection. CD8 T cells
      specific for the noninflationary M45 epitope displayed a classic central memory
      phenotype, re-expressing the lymph node homing receptor CD62L and homeostatic
      cytokine receptors for IL-7 and IL-15, and produced low levels of IL-2. Responses
      to two inflationary epitopes, m139 and IE3, retained an effector memory surface
      phenotype (CD62L(low), IL-7Ralpha(-), IL-15Rbeta(-)) and were unable to produce
      IL-2. We suggest that immunological choices are superimposed on altered viral
      gene expression profiles to determine immunodominance during chronic murine CMV
      infection.

PMID- 16785543
TI  - Pneumocystis cell wall beta-glucans induce dendritic cell costimulatory molecule
      expression and inflammatory activation through a Fas-Fas ligand mechanism.
AB  - Respiratory failure during Pneumocystis pneumonia is mainly a consequence of
      exaggerated inflammatory responses to the organism. Dendritic cells (DCs) are the
      most potent APCs in the lung and are key to the regulation of innate and adaptive
      immune responses. However, their participation in the inflammatory response
      directed against Pneumocystis infection has not been fully elucidated. Therefore,
      we studied the role of Pneumocystis carinii, as well as Saccharomyces cerevisiae,
      cell wall-derived beta-glucans, in DC costimulatory molecule expression. We
      further studied the impact of beta-glucans on subsequent T cell activation.
      Because cytokine secretion by DCs has recently been shown to be regulated by Fas
      ligand (FasL), its role in beta-glucan activation of DCs was also investigated.
      beta-Glucan-induced DC activation occurred in part through dectin-1 receptors. We
      demonstrated that DC activation by beta-glucans elicits T cell activation and
      polarization into a Th1 patterned response, but with the conspicuous absence of
      IL-12. These observations differed from LPS-driven T cell polarization,
      suggesting that beta-glucans and LPS signal DC activation through different
      mechanisms. We additionally determined that IL-1beta and TNF-alpha secretion by
      beta-glucan-stimulated DCs was partially regulated by Fas-FasL. This suggests
      that dysregulation of FasL could further enhance exuberant and prolonged cytokine
      production by DCs following DC-T cell interactions, further promoting lung
      inflammation typical of Pneumocystis pneumonia.

PMID- 16785544
TI  - Impaired generation of reactive oxygen species during differentiation of
      dendritic cells (DCs) by Mycobacterium tuberculosis secretory antigen (MTSA) and
      subsequent activation of MTSA-DCs by mycobacteria results in increased
      intracellular survival.
AB  - We investigated the role of reactive oxygen species (ROS) in dendritic cell (DC)
      differentiation by 10-kDa Mycobacterium tuberculosis secretory Ag (MTSA) and
      survival of mycobacteria therein. Compared with GM-CSF, MTSA induced lower ROS
      production during DC differentiation from precursors. This result correlated with
      higher superoxide dismutase 1 expression in MTSA stimulated precursors as
      compared with GM-CSF stimulation. Furthermore, a negative regulation of protein
      kinase C (PKC) activation by ROS was observed during DC differentiation. ROS
      inhibited the rapid and increased phosphorylation of PKCalpha observed during DC
      differentiation by MTSA. In contrast, ROS inhibition increased the weak and
      delayed PKCalpha phosphorylation by GM-CSF. Similar to DC differentiation, upon
      activation with either M. tuberculosis cell extract (CE) or live Mycobacterium
      bovis bacillus Calmette-Guerin (BCG), DCs differentiated with MTSA (MTSA-DCs)
      generated lower ROS levels when compared with DCs differentiated with GM-CSF (GM
      CSF-DCs). Likewise, a negative regulation of PKCalpha phosphorylation by ROS was
      once again observed in DCs activated with either M. tuberculosis CE or live M.
      bovis BCG. However, a reciprocal positive regulation between ROS and calcium was
      observed. Compared with MTSA-DCs, stimulation of GM-CSF-DCs with M. tuberculosis
      CE induced a 2-fold higher ROS-dependent calcium influx. However, pretreatment of
      MTSA-DCs with H(2)O(2) increased calcium mobilization. Finally, lower ROS levels
      in MTSA-DCs correlated with increased intracellular survival of M. bovis BCG when
      compared with survival in GM-CSF-DCs. Although inhibiting ROS in GM-CSF-DCs
      increased M. bovis BCG survival, H(2)O(2) treatment of MTSA-DCs decreased
      survival of M. bovis BCG. Overall our results suggest that DCs differentiated
      with Ags such as MTSA may provide a niche for survival and/or growth of
      mycobacteria following sequestration of ROS.

PMID- 16785545
TI  - Altered CD4+ T cell phenotype and function determine the susceptibility to
      mucosal candidiasis in transgenic mice expressing HIV-1.
AB  - The impairments of protective mucosal immunity which cause susceptibility to
      oropharyngeal candidiasis (OPC) in HIV infection remain undefined. This study
      used a model of OPC in CD4C/HIV MutA transgenic (Tg) mice expressing Rev, Env,
      and Nef of HIV-1 to investigate the role of transgene expressing dendritic cells
      (DCs) and CD4+ T cells in maintenance of chronic oral carriage of Candida
      albicans. DCs were depleted in the Tg mice and had an immature phenotype, with
      low expression of MHC class II and IL-12. CD4+ T cells were quantitatively
      reduced in the oral mucosa, cervical lymph nodes (CLNs) and peripheral blood of
      the Tg mice, and displayed a polarization toward a nonprotective Th2 response.
      Proliferation of CLN CD4+ T cells from infected Tg mice in response to C.
      albicans Ag in vitro was abrogated and the cells failed to acquire an effector
      phenotype. Coculture of C. albicans-pulsed DCs with CD4+ T cells in vitro showed
      that Tg expression in either or both of these cell populations sharply reduced
      the proliferation of CD4+ T cells and their production of IL-2. Finally, transfer
      of naive non-Tg CD4+ T cells into these Tg mice restored proliferation to C.
      albicans Ag and sharply reduced oral burdens of C. albicans. Overall, these
      results indicate that defective CD4+ T cells primarily determine the
      susceptibility to chronic carriage of C. albicans in these Tg mice.

PMID- 16785546
TI  - Evaluation of immunological paradigms in a virus model: are dendritic cells
      critical for antiviral immunity and viral clearance?
AB  - We have examined the role of dendritic cells (DCs) in the antiviral immune
      response and viral clearance using a transgenic mouse model (CD11c-diphtheria
      toxin (DT) receptor GFP) that allows for their conditional ablation in vivo. DT
      administration systemically ablated conventional and IFN-producing plasmacytoid
      DCs (pDCs) in transgenic, but not nontransgenic littermates, without elimination
      of splenic macrophages. Unexpectedly, early (12 and 48 h postinfection) viral
      clearance of vesicular stomatitis virus was normal in DC-depleted mice despite
      markedly reduced serum titers of type I IFN. DC-depleted mice remained virus-free
      with the exception of a subset (approximately 30%) that developed overwhelming
      and fatal brain infections 6 days postinfection. However, DT treatment profoundly
      inhibited clonal expansion of naive CD8+ vesicular stomatitis virus-specific T
      cells without altering the primary Th1 and Th2 cytokine response. Optimal clonal
      expansion required pDCs because selective elimination of these cells in vivo with
      a depleting Ab also suppressed expansion of tetramer+ cells, although Th1/Th2
      cytokine production remained unaltered. Collectively, these data indicate that
      conventional DCs and to a lesser extent pDCs are critical for proliferation of
      naive antiviral T cells. However, other components of the primary adaptive immune
      response (Th1/Th2 cytokines) are essentially normal in the absence of DCs, which
      may account for the efficient viral clearance seen in DC-depleted mice. Thus,
      sufficient redundancy exists in the immune system to sustain efficient viral
      clearance despite loss of an APC considered essential for induction of a primary
      antiviral immune response.

PMID- 16785547
TI  - The meningococcal vaccine candidate GNA1870 binds the complement regulatory
      protein factor H and enhances serum resistance.
AB  - Neisseria meningitidis binds factor H (fH), a key regulator of the alternative
      complement pathway. A approximately 29 kD fH-binding protein expressed in the
      meningococcal outer membrane was identified by mass spectrometry as GNA1870, a
      lipoprotein currently under evaluation as a broad-spectrum meningococcal vaccine
      candidate. GNA1870 was confirmed as the fH ligand on intact bacteria by 1)
      abrogation of fH binding upon deleting GNA1870, and 2) blocking fH binding by
      anti-GNA1870 mAbs. fH bound to whole bacteria and purified rGNA1870 representing
      each of the three variant GNA1870 families. We showed that the amount of fH
      binding correlated with the level of bacterial GNA1870 expression. High levels of
      variant 1 GNA1870 expression (either by allelic replacement of gna1870 or by
      plasmid-driven high-level expression) in strains that otherwise were low-level
      GNA1870 expressers (and bound low amounts of fH by flow cytometry) restored high
      levels of fH binding. Diminished fH binding to the GNA1870 deletion mutants was
      accompanied by enhanced C3 binding and increased killing of the mutants.
      Conversely, high levels of GNA1870 expression and fH binding enhanced serum
      resistance. Our findings support the hypothesis that inhibiting the binding of a
      complement down-regulator protein to the neisserial surface by specific Ab may
      enhance intrinsic bactericidal activity of the Ab, resulting in two distinct
      mechanisms of Ab-mediated vaccine efficacy. These data provide further support
      for inclusion of this molecule in a meningococcal vaccine. To reflect the
      critical function of this molecule, we suggest calling it fH-binding protein.

PMID- 16785549
TI  - The peptidoglycan-degrading property of lysozyme is not required for bactericidal
      activity in vivo.
AB  - Lysozyme is an abundant, cationic antimicrobial protein that plays an important
      role in pulmonary host defense. Increased concentration of lysozyme in the
      airspaces of transgenic mice enhanced bacterial killing whereas lysozyme
      deficiency resulted in increased bacterial burden and morbidity. Lysozyme
      degrades peptidoglycan in the bacterial cell wall leading to rapid killing of
      Gram-positive organisms; however, this mechanism cannot account for the
      protective effect of lysozyme against Gram-negative bacteria. The current study
      was therefore designed to test the hypothesis that the catalytic activity
      (muramidase activity) of lysozyme is not required for bacterial killing in vivo.
      Substitution of serine for aspartic acid at position 53 (D53S) in mouse lysozyme
      M completely ablated muramidase activity. Muramidase-deficient recombinant
      lysozyme (LysM(D53S)) killed both Gram-positive and Gram-negative bacteria in
      vitro. Targeted expression of LysM(D53S) in the respiratory epithelium of wild
      type (LysM(+/+)/LysM(D53S)) or lysozyme M(null) mice (LysM(-/-)/LysM(D53S))
      resulted in significantly elevated lysozyme protein in the airspaces without any
      increase in muramidase activity. Intratracheal challenge of transgenic mice with
      Gram-positive or Gram-negative bacteria resulted in a significant increase in
      bacterial burden in LysM(-/-) mice that was completely reversed by targeted
      expression of LysM(D53S). These results indicate that the muramidase activity of
      lysozyme is not required for bacterial killing in vitro or in vivo.

PMID- 16785548
TI  - Persistence and function of central and effector memory CD4+ T cells following
      infection with a gastrointestinal helminth.
AB  - Immunity in the gastrointestinal tract is important for resistance to many
      pathogens, but the memory T cells that mediate such immunity are poorly
      characterized. In this study, we show that following sterile cure of a primary
      infection with the gastrointestinal parasite Trichuris muris, memory CD4+ T cells
      persist in the draining mesenteric lymph node and protect mice against
      reinfection. The memory CD4+ T cells that developed were a heterogeneous
      population, consisting of both CD62L(high) central memory T cells (T(CM)) and
      CD62L(low) effector memory T cells (T(EM)) that were competent to produce the Th
      type 2 effector cytokine, IL-4. Unlike memory T cells that develop following
      exposure to several other pathogens, both CD4+ T(CM) and T(EM) populations
      persisted in the absence of chronic infection, and, critically, both populations
      were able to transfer protective immunity to naive recipients. CD62L(high)CD4+
      T(CM) were not apparent early after infection, but emerged following clearance of
      primary infection, suggesting that they may be derived from CD4+ T(EM).
      Consistent with this theory, transfer of CD62L(low)CD4+ T(EM) into naive
      recipients resulted in the development of a population of protective
      CD62L(high)CD4+ T(CM). Taken together, these studies show that distinct subsets
      of memory CD4+ T cells develop after infection with Trichuris, persist in the
      GALT, and mediate protective immunity to rechallenge.

PMID- 16785550
TI  - Stat3 is required for cytoprotection of the respiratory epithelium during
      adenoviral infection.
AB  - The role of Stat3 in the maintenance of pulmonary homeostasis following
      adenoviral-mediated lung injury was assessed in vivo. Stat3 was selectively
      deleted from bronchiolar and alveolar epithelial cells in Stat3(DeltaDelta) mice.
      Although lung histology and function were unaltered by deletion of Stat3 in vivo,
      Stat3(DeltaDelta) mice were highly susceptible to lung injury caused by
      intratracheal administration of AV1-GFP, an early (E) region 1- and E3-deleted,
      nonproliferative adenovirus. Severe airspace enlargement, loss of alveolar
      septae, and sloughing of the bronchiolar epithelium were observed in
      Stat3(DeltaDelta) mice as early as 1 day after exposure to the virus. Although
      surfactant protein A, B, and C content and surfactant protein-B mRNA expression
      in Stat3(DeltaDelta) mice were similar, TUNEL staining and caspase-3 were
      increased in alveolar type II epithelial cells of Stat3(DeltaDelta) mice after
      exposure to virus. RNA microarray analysis of type II epithelial cells isolated
      from Stat3(DeltaDelta) mice demonstrated significant changes in expression of
      numerous genes, including those genes regulating apoptosis, supporting the
      concept that the susceptibility of Stat3-deficient mice to adenovirus was related
      to the role of Stat3 in the regulation of cell survival. AV1-Bcl-x(L), an E1- and
      E3-deleted, nonproliferative adenovirus expressing the antiapoptotic protein Bcl
      x(L), protected Stat3(DeltaDelta) mice from adenoviral-induced lung injury.
      Adenoviral infection of the lungs of Stat3-deficient mice was associated with
      severe injury of the alveolar and bronchiolar epithelium. Thus, Stat3 plays a
      critical cytoprotective role that is required for epithelial cell survival and
      maintenance of alveolar structures during the early phases of pulmonary
      adenoviral infection.

PMID- 16785551
TI  - Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of
      antibacterial defense in the lung against Klebsiella pneumoniae but not
      Pseudomonas aeruginosa.
AB  - Bacterial pneumonia is a leading cause of mortality and is associated with
      extensive neutrophil accumulation. Major pathogens associated with this disease
      include nonflagellated Klebsiella pneumoniae (Kp) and flagellated Pseudomonas
      aeruginosa (Pa). TLRs are essential for innate immune defense. TIRAP (Toll/IL-1R
      domain-containing adaptor protein) is an adaptor in TLR1, TLR2, TLR4, and TLR6
      signaling, whereas MyD88 is an adaptor for all TLRs. However, the importance of
      TIRAP in pulmonary defense against Kp or Pa has not been examined. To demonstrate
      the role of TIRAP, TIRAP-deficient and wild-type littermates were intratracheally
      inoculated with Kp or Pa. We found that TIRAP(-/-) mice had substantial
      mortality, higher bacterial burden in the lungs, and enhanced dissemination
      following Kp challenge. Furthermore, Kp-induced neutrophil sequestration,
      histopathology, and MIP-2, TNF-alpha, IL-6, and LIX (lipopolysaccharide-induced
      CXC chemokine) production were attenuated in the lungs of TIRAP(-/-) mice. In
      contrast, TIRAP is not required for Pa-induced mortality, pulmonary bacterial
      burden, bacterial dissemination, neutrophil accumulation, or histopathology, yet
      it is necessary for MIP-2, TNF-alpha, and IL-6 production, but not LIX
      production. However, both Kp- and Pa-induced neutrophil influxes are MyD88
      dependent. To determine the mechanisms associated with Pa-induced neutrophil
      accumulation, we inoculated mice with a flagellin C mutant of Pa (PaDeltafliC) or
      purified flagellin, a TLR5 agonist. PaDeltafliC-induced neutrophil sequestration
      and LIX expression are dependent on TIRAP, whereas flagellin-induced neutrophil
      influx and LIX expression are independent of TIRAP. These novel findings
      illustrate a pathogen-specific role for TIRAP in pulmonary defense and suggest
      that TLR5 plays an essential role for Pa-induced neutrophil influx via LIX
      production.

PMID- 16785552
TI  - SIGIRR promotes resistance against Pseudomonas aeruginosa keratitis by down
      regulating type-1 immunity and IL-1R1 and TLR4 signaling.
AB  - Pseudomonas aeruginosa keratitis destroys the cornea in susceptible Th1 responder
      C57BL/6 (B6), but not resistant Th2 responder (BALB/c) mice. To determine whether
      single Ig IL-1R-related molecule (SIGIRR) played a role in resistance, mRNA and
      protein expression levels were tested. Both were constitutively expressed in the
      cornea of the two mouse groups. A disparate mRNA and protein expression pattern
      was detected in the cornea of BALB/c vs B6 mice after infection. SIGIRR protein
      decreased significantly in BALB/c over B6 mice at 1 day postinfection. Thus,
      BALB/c mice were injected with an anti-SIGIRR Ab or IgG control. Anti-SIGIRR Ab
      over control-treated mice showed increased corneal opacity, stromal damage, and
      bacterial load. Corneal mRNA levels for IL-1beta, MIP-2, IL-1R1, TLR4, IL-18, and
      IFN-gamma and protein levels for IL-1beta and MIP-2 also were significantly up
      regulated in anti-SIGIRR Ab over control mice, while no changes in
      polymorphonuclear cell number, IL-4, or IL-10 mRNA expression were detected. To
      further define the role of SIGIRR, RAW264.7 macrophage-like cells were
      transiently transfected with SIGIRR and stimulated with heat-killed P. aeruginosa
      or LPS. SIGIRR transfection significantly decreased mRNA levels for IL-1R1, TLR4,
      and type 1 immune response-associated cytokines (IL-12, IL-18, and IFN-gamma) as
      well as proinflammatory cytokines IL-1beta and MIP-2 protein expression. SIGIRR
      also negatively regulated IL-1 and LPS, but not poly(I:C)-mediated signaling and
      NF-kappaB activation. These data provide evidence that SIGIRR is critical in
      resistance to P. aeruginosa corneal infection by down-regulating type 1 immunity,
      and that it negatively regulates IL-1 and TLR4 signaling.

PMID- 16785553
TI  - Agonistic monoclonal antibody against CD40 receptor decreases lymphocyte
      apoptosis and improves survival in sepsis.
AB  - Sepsis causes a marked apoptosis-induced depletion of lymphocytes. The degree of
      lymphocyte apoptosis during sepsis strongly correlates with survival. CD40, a
      member of the TNFR family, is expressed on APCs and has potent antiapoptotic
      activity. In this study we determined whether an agonistic Ab against CD40 could
      protect lymphocytes from sepsis-induced apoptosis. Secondly, we examined
      potential antiapoptotic mechanisms of the putative protection. Lastly, we aimed
      to determine whether anti-CD40 treatment could improve survival in sepsis. CD1
      mice were made septic by the cecal ligation and puncture method and treated
      postoperatively with anti-CD40 Ab. Treatment with anti-CD40 completely abrogated
      sepsis-induced splenic B cell death and, surprisingly, decreased splenic and
      thymic T cell death as well (p < 0.001). To investigate the mechanism of
      protection of anti-CD40 therapy on T cells, CD40 receptor expression was
      examined. As anticipated, the CD40 receptor was constitutively expressed on B
      cells, but, unexpectedly, splenic and thymic T cells were found to express CD40
      receptor during sepsis. Furthermore, CD4+CD8- T cells were the predominant
      subtype of T cells expressing CD40 receptor during sepsis. Additionally, the
      antiapoptotic protein Bcl-x(L) was found to be markedly increased in splenic B
      and T cells as well as in thymic T cells after treatment with anti-CD40 Ab (p <
      0.0025). Lastly, mice that were made septic in a double injury model of sepsis
      had improved survival after treatment with anti-CD40 as compared with controls (p
      = 0.05). In conclusion, anti-CD40 treatment increases Bcl-x(L), provides nearly
      complete protection against sepsis-induced lymphocyte apoptosis, and improves
      survival in sepsis.

PMID- 16785554
TI  - IL-17 plays an important role in the development of experimental autoimmune
      encephalomyelitis.
AB  - IL-17 is a proinflammatory cytokine that activates T cells and other immune cells
      to produce a variety of cytokines, chemokines, and cell adhesion molecules. This
      cytokine is augmented in the sera and/or tissues of patients with contact
      dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL
      17 is involved in the development of autoimmune arthritis and contact, delayed,
      and airway hypersensitivity in mice. As the expression of IL-17 is also augmented
      in multiple sclerosis, we examined the involvement of this cytokine in these
      diseases using IL-17(-/-) murine disease models. We found that the development of
      experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple
      sclerosis, was significantly suppressed in IL-17(-/-) mice; these animals
      exhibited delayed onset, reduced maximum severity scores, ameliorated
      histological changes, and early recovery. T cell sensitization against myelin
      oligodendrocyte glycoprotein was reduced in IL-17(-/-) mice upon sensitization.
      The major producer of IL-17 upon treatment with myelin digodendrocyte
      glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of
      IL-17(-/-) CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL
      17-producing T cells were increased in IFN-gamma(-/-) cells, while IFN-gamma
      producing cells were increased in IL-17(-/-) cells, suggesting that IL-17 and IFN
      gamma mutually regulate IFN-gamma and IL-17 production. These observations
      indicate that IL-17 rather than IFN-gamma plays a crucial role in the development
      of EAE.

PMID- 16785555
TI  - Transcellular secretion of group V phospholipase A2 from epithelium induces beta
      2-integrin-mediated adhesion and synthesis of leukotriene C4 in eosinophils.
AB  - We examined the mechanism by which secretory group V phospholipase A(2)
      (gVPLA(2)) secreted from stimulated epithelial cells activates eosinophil
      adhesion to ICAM-1 surrogate protein and secretion of leukotriene (LT)C(4).
      Exogenous human group V PLA(2) (hVPLA(2)) caused an increase in surface CD11b
      expression and focal clustering of this integrin, which corresponded to increased
      beta(2) integrin-mediated adhesion. Human IIaPLA(2), a close homolog of hVPLA(2),
      or W31A, an inactive mutant of hVPLA(2), did not affect these responses.
      Exogenous lysophosphatidylcholine but not arachidonic acid mimicked the beta(2)
      integrin-mediated adhesion caused by hVPLA(2) activation. Inhibition of hVPLA(2)
      with MCL-3G1, a mAb against gVPLA(2), or with LY311727, a global secretory
      phospholipase A(2) (PLA(2)) inhibitor, attenuated the activity of hVPLA(2);
      trifluoromethylketone, an inhibitor of cytosolic group IVA PLA(2) (gIVA-PLA(2)),
      had no inhibitory effect on hVPLA(2)-mediated adhesion. Activation of beta(2)
      integrin-dependent adhesion by hVPLA(2) did not cause ERK1/2 activation and was
      independent of gIVA-PLA(2) phosphorylation. In other studies, eosinophils
      cocultured with epithelial cells were stimulated with FMLP/cytochalasin B
      (FMLP/B) and/or endothelin-1 (ET-1) before LTC(4) assay. FMLP/B alone caused
      release of LTC(4) from eosinophils, which was augmented by coculture with
      epithelial cells activated with ET-1. Addition of MCL-3G1 to cocultured cells
      caused approximately 50% inhibition of LTC(4) secretion elicited by ET-1, which
      was blocked further by trifluoromethylketone. Our data indicate that hVPLA(2)
      causes focal clustering of CD11b and beta(2) integrin adhesion by a novel
      mechanism that is independent of arachidonic acid synthesis and gIVA-PLA(2)
      activation. We also demonstrate that gVPLA(2), endogenously secreted from
      activated epithelial cells, promotes secretion of LTC(4) in cocultured
      eosinophils.

PMID- 16785556
TI  - A mechanism for neurodegeneration induced by group B streptococci through
      activation of the TLR2/MyD88 pathway in microglia.
AB  - Group B Streptococcus (GBS) is a major cause of bacterial meningitis and
      neurological morbidity in newborn infants. The cellular and molecular mechanisms
      by which this common organism causes CNS injury are unknown. We show that both
      heat-inactivated whole GBS and a secreted proteinaceous factor from GBS (GBS-F)
      induce neuronal apoptosis via the activation of murine microglia through a TLR2
      dependent and MyD88-dependent pathway in vitro. Microglia, astrocytes, and
      oligodendrocytes, but not neurons, express TLR2. GBS as well as GBS-F induce the
      synthesis of NO in microglia derived from wild-type but not TLR2(-/-) or MyD88(-/
      ) mice. Neuronal death in neuronal cultures complemented with wild-type microglia
      is NO-dependent. We show for the first time a TLR-mediated mechanism of neuronal
      injury induced by a clinically relevant bacterium. This study demonstrates a
      causal molecular relationship between infection with GBS, activation of the
      innate immune system in the CNS through TLR2, and neurodegeneration. We suggest
      that this process contributes substantially to the serious morbidity associated
      with neonatal GBS meningitis and may provide a potential therapeutic target.

PMID- 16785557
TI  - Epithelial inflammation is associated with CCL28 production and the recruitment
      of regulatory T cells expressing CCR10.
AB  - Mucosal tissues require constant immune surveillance to clear harmful pathogens
      while maintaining tolerance to self Ags. Regulatory T cells (Tregs) play a
      central role in this process and expression of alpha(E)beta(7) has been reported
      to define a subset of Tregs with tropism for inflamed tissues. However, the
      signals responsible for recruiting Tregs to epithelial surfaces are poorly
      understood. We have isolated a subset of CCR10-expressing CD25+CD4+Foxp3+ Tregs
      with potent anti-inflammatory properties from chronically inflamed human liver.
      The CCR10+ Tregs were detected around bile ducts that expressed increased levels
      of the CCR10 ligand CCL28. CCL28 was secreted by primary human cholangiocytes in
      vitro in response to LPS, IL-1beta, or bile acids. Exposure of CCR10+ Tregs to
      CCL28 in vitro stimulated migration and adhesion to mucosal addressin cell
      adhesion molecule-1 and VCAM-1. Liver-derived CCR10+ Tregs expressed low levels
      of CCR7 but high levels of CXCR3, a chemokine receptor associated with
      infiltration into inflamed tissue and contained a subset of alpha(E)beta7(+)
      cells. We propose that CXCR3 promotes the recruitment of Tregs to inflamed
      tissues and CCR10 allows them to respond to CCL28 secreted by epithelial cells
      resulting in the accumulation of CCR10+ Tregs at mucosal surfaces.

PMID- 16785558
TI  - The Src family kinases Hck and Fgr are dispensable for inside-out,
      chemoattractant-induced signaling regulating beta 2 integrin affinity and valency
      in neutrophils, but are required for beta 2 integrin-mediated outside-in
      signaling involved in sustained adhesion.
AB  - Neutrophil beta(2) integrins are activated by inside-out signaling regulating
      integrin affinity and valency; following ligand binding, beta(2) integrins
      trigger outside-in signals regulating cell functions. Addressing inside-out and
      outside-in signaling in hck(-/-)fgr(-/-) neutrophils, we found that Hck and Fgr
      do not regulate chemoattractant-induced activation of beta(2) integrin affinity.
      In fact, beta(2) integrin-mediated rapid adhesion, in static condition assays,
      and neutrophil adhesion to glass capillary tubes cocoated with ICAM-1, P
      selectin, and a chemoattractant, under flow, were unaffected in hck(-/-)fgr(-/-)
      neutrophils. Additionally, examination of integrin affinity by soluble ICAM-1
      binding assays and of beta(2) integrin clustering on the cell surface, showed
      that integrin activation did not require Hck and Fgr expression. However, after
      binding, hck(-/-)fgr(-/-) neutrophil spreading over beta(2) integrin ligands was
      reduced and they rapidly detached from the adhesive surface. Whether alterations
      in outside-in signaling affect sustained adhesion to the vascular endothelium in
      vivo was addressed by examining neutrophil adhesiveness to inflamed muscle
      venules. Intravital microscopy analysis allowed us to conclude that Hck and Fgr
      regulate neither the number of rolling cells nor rolling velocity in neutrophils.
      However, arrest of hck(-/-)fgr(-/-) neutrophils to >60 microm in diameter venules
      was reduced. Thus, Hck and Fgr play no role in chemoattractant-induced inside-out
      beta(2) integrin activation but regulate outside-in signaling-dependent sustained
      adhesion.

PMID- 16785559
TI  - Adenoviral-mediated overexpression of SOCS3 enhances IgG immune complex-induced
      acute lung injury.
AB  - The lung inflammatory response caused by intratracheal deposition of IgG immune
      complexes (IC) includes the production of IL-6, which signals through activation
      of STAT transcription factors. Recently, suppressor of cytokine signaling 3
      (SOCS3) has been shown to be a key negative regulator of IL-6/gp130/Jak/STAT3
      signal transduction. Although SOCS3 has been implicated in several inflammatory
      diseases, very little is known regarding its activation and its function in the
      lung during acute inflammation. Our previous study showed that IL-6/STAT3
      activation was triggered in lungs after intrapulmonary deposition of IgG IC in
      rats. In the current study, we sought to determine whether SOCS3 is playing a
      regulatory role in the lung inflammatory response. SOCS3 induction occurred
      during development of inflammation in the IgG IC model of lung injury.
      Overexpression of SOCS3 in lung using a recombinant adenovirus encoding murine
      SOCS3 resulted in substantial increases in lung vascular permeability and lung
      myeloperoxidase, together with enhanced levels of TNF-alpha, MIP-2, and
      keratinocyte-activated cytokine in bronchoalveolar lavage fluids. SOCS3
      overexpression in lungs led to overproduction of bronchoalveolar lavage IL-6, but
      not IL-10, in this inflammatory model. We further show that activation of STAT3
      was inhibited by SOCS3 overexpression as well as by anti-IL-6 treatment during
      IgG IC-induced lung injury, as determined by EMSA. In vitro, SOCS3 overexpression
      abrogated IL-6-induced activation of STAT3 in lung epithelial cells. These
      findings suggest SOCS3 is an important regulator of lung inflammatory injury
      after deposition of IgG IC.

PMID- 16785560
TI  - Gender differences in murine airway responsiveness and lipopolysaccharide-induced
      inflammation.
AB  - The roles of gender and sex hormones in lung function and disease are complex and
      not completely understood. The present study examined the influence of gender on
      lung function and respiratory mechanics in naive mice and on acute airway
      inflammation and hyperresponsiveness induced by intratracheal LPS administration.
      Basal lung function characteristics did not differ between naive males and
      females, but males demonstrated significantly greater airway responsiveness than
      females following aerosolized methacholine challenge as evidenced by increased
      respiratory system resistance and elastance (p < 0.05). Following LPS
      administration, males developed more severe hypothermia and greater airway
      hyperresponsiveness than females (p < 0.05). Inflammatory indices including
      bronchoalveolar lavage fluid total cells, neutrophils, and TNF-alpha content were
      greater in males than in females 6 h following LPS administration (p < 0.05),
      whereas whole-lung TLR-4 protein levels did not differ among treatment groups,
      suggesting that differential expression of TLR-4 before or after LPS exposure did
      not underlie the observed inflammatory outcomes. Gonadectomy decreased airway
      inflammation in males but did not alter inflammation in females, whereas
      administration of exogenous testosterone to intact females increased their
      inflammatory responses to levels observed in intact males. LPS-induced airway
      hyperresponsiveness was also decreased in castrated males and was increased in
      females administered exogenous testosterone. Collectively, these data indicate
      that airway responsiveness in naive mice is influenced by gender, and that male
      mice have exaggerated airway inflammatory and functional responses to LPS
      compared with females. These gender differences are mediated, at least in part,
      by effects of androgens.

PMID- 16785561
TI  - Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute
      lung inflammation.
AB  - Glucocorticoid-induced TNFR-related gene (GITR) participates in the
      immune/inflammatory response. Because GITR expression has been described in cells
      other than T lymphocytes, we investigated whether it also modulates acute
      inflammatory response. Using GITR-deficient (GITR(-/-)) mice, we analyzed the
      role of GITR in the development of carrageenan-induced lung inflammation
      (pleurisy) by studying several proinflammatory markers 2-8 h after carrageenan
      injection. When compared with GITR(+/+), GITR(-/-) mice exhibited decreased
      production of turbid exudate containing a lower number of leukocytes. This was
      correlated with the reduction of inflammatory markers (including TNF-alpha, IL
      1beta, myeloperoxidase, inducible NO synthase, and cyclooxygenase 2) in the
      pleural exudate and/or in the lung. Moreover, endothelial cells expressed lower
      levels of adhesion molecules. In lungs of GITR(+/+) mice, GITR ligand expression
      was not modulated during pleurisy, while that of GITR increased, as a consequence
      of increased infiltration by GITR-expressing cells and of GITR up-regulation in
      macrophages and endothelial cells. Finally, cotreatment of GITR(+/+) mice with
      carrageenan and Fc-GITR fusion protein decreased the number of inflammatory cells
      (pleural macrophages and lung neutrophils) as compared with carrageenan treatment
      alone, confirming that GITR plays a role in the modulation of pleurisy.

PMID- 16785562
TI  - A regulatory effect of the balance between TNF-alpha and IL-6 in the
      granulomatous and inflammatory response to Rhodococcus aurantiacus infection in
      mice.
AB  - After i.v. inoculation with Rhodococcus aurantiacus, wild-type (WT) mice develop
      nonnecrotic, epithelioid granulomas. Because a high level of TNF-alpha is
      observed during the initial phase postinfection, we examined the extent to which
      TNF-alpha contributes to granulomatous inflammation using TNF-alpha gene
      deficient (TNF-alpha(-/-)) mice. Despite a lack of R. aurantiacus proliferation,
      TNF-alpha(-/-) mice displayed high mortality rates within 5 days postinfection,
      as well as a high level of IL-6 in their spleens. Histological examination showed
      an absence of granuloma formation in TNF-alpha(-/-) mice. Pretreatment of TNF
      alpha(-/-) mice with rTNF-alpha failed to restore this granuloma formation but
      accelerated bacterial removal and cellular recruitment. This rTNF-alpha
      administration also attenuated IL-6 production, resulting in increased survival
      rates of TNF-alpha(-/-) mice. Heat-killed R. aurantiacus induced in vitro
      enhanced mRNA expression and production of IL-6 in macrophages and DCs from TNF
      alpha(-/-) mice when compared with WT controls, and treatment of TNF-alpha(-/-)
      mouse cells with rTNF-alpha decreased the IL-6 secretion. Moreover, anti-TNF
      alpha or anti-IL-6 treatment increased IL-6 or TNF-alpha production by WT mouse
      cells, respectively. These data suggest that the production of TNF-alpha and IL-6
      can be negatively regulated by each other. Administration of rIFN-gamma to TNF
      alpha(-/-) mice caused immature granulomas in livers, and treatment with both
      rTNF-alpha and rIFN-gamma led to the formation of mature granulomas. Overall, TNF
      alpha appears crucial for bacterial clearance, cellular recruitment, and
      granuloma formation. The balance between TNF-alpha and IL-6 during the early
      phase of infection controls the development of the inflammatory response to R.
      aurantiacus infection.

PMID- 16785563
TI  - Lovastatin-induced apoptosis in macrophages through the Rac1/Cdc42/JNK pathway.
AB  - Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, have been
      used successfully in the treatment of hypercholesterolemia for more than a
      decade. Statins also exhibit overall clinical benefits on cardiovascular diseases
      independent of their effects on lowering serum cholesterol levels. These
      beneficial effects of statin therapy are believed to be due, at least in part, to
      the anti-inflammatory and immunomodulatory roles of statins. Statin treatment
      reduces the levels of inflammatory markers, decreases the activation and
      recruitment of immune cells, and delays the progression of atherosclerosis, a
      chronic inflammatory disease. However, little is known about the direct impact of
      statins on immune cells, particularly on macrophages. We report that lovastatin,
      a member of the statin family, effectively induces apoptosis in macrophages.
      Further investigation of the molecular mechanism has revealed that Rac1 and
      Cdc42, the small GTPase family members, may play an important role in lovastatin
      induced macrophage apoptosis. Moreover, the activation of the JNK pathway may
      contribute to this event. Our findings provide a better understanding of the
      molecular basis underlying the anti-inflammatory clinical benefits of statin
      therapy in cardiovascular diseases.

PMID- 16785564
TI  - Identification of a TLR-independent pathway for Borrelia burgdorferi-induced
      expression of matrix metalloproteinases and inflammatory mediators through
      binding to integrin alpha 3 beta 1.
AB  - Borrelia burgdorferi stimulates a robust inflammatory response at sites of
      localization. Binding of borrelial lipoproteins to TLR-2 is one pathway important
      in the host response to B. burgdorferi. However, while TLR-2 is clearly important
      in control of infection, inflammation is actually worsened in the absence of TLR
      2 or the shared TLR adapter molecule, MyD88, suggesting that there are
      alternative pathways regulating inflammation. Integrins are cell surface
      receptors that play an important role in cell to cell communications and that can
      activate inflammatory signaling pathways. In this study, we report for the first
      time that B. burgdorferi binds to integrin alpha(3)beta(1) and that binding of B.
      burgdorferi to this integrin results in induction of proinflammatory cytokines,
      chemokines, and end-effector molecules such as matrix metalloproteinases in
      primary human chondrocyte cells. Expression of these same molecules is not
      affected by the absence of MyD88 in murine articular cartilage, suggesting that
      the two pathways act independently in activating host inflammatory responses to
      B. burgdorferi. B. burgdorferi-induced alpha(3) signaling is mediated by JNK, but
      not p38 MAPK. In summary, we have identified a new host receptor for B.
      burgdorferi, integrin alpha(3)beta(1); binding of B. burgdorferi to integrin
      alpha(3)beta(1) results in the release of inflammatory mediators and is proposed
      as a TLR-independent pathway for activation of the innate immune response by the
      organism.

PMID- 16785565
TI  - C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated
      transcription in TNF-tolerant cells.
AB  - TNF is a major mediator of inflammation, immunity, and apoptosis. Pre-exposure to
      TNF reduces sensitivity to restimulation, a phenomenon known as tolerance,
      considered as protective in sepsis, but also as a paradigm for immunoparalysis.
      Earlier experiments in TNF-tolerant cells display inhibition of NF-kappaB
      dependent IL-8 gene expression at the transcriptional level with potential
      involvement of C/EBPbeta. In this study, we have shown that a kappaB motive was
      sufficient to mediate transcriptional inhibition under TNF tolerance conditions
      in monocytic cells. Furthermore, in tolerant cells, TNF-induced NF-kappaB p65
      phosphorylation was markedly decreased, which was accompanied by the formation of
      C/EBPbeta-p65 complexes. Remarkably, in C/EBPbeta(-/-) cells incubated under the
      conditions of TNF tolerance, neither impairment of transcription nor inhibition
      of p65 phosphorylation was observed. Finally, we showed that C/EBPbeta
      overexpression reduced p65-mediated transactivation and that association of
      C/EBPbeta with p65 specifically prevented p65 phosphorylation. Our data
      demonstrate that C/EBPbeta is an essential signaling component for inhibition of
      NF-kappaB-mediated transcription in TNF-tolerant cells and suggest that this is
      caused by blockade of p65 phosphorylation. These results define a new molecular
      mechanism responsible for TNF tolerance in monocytic cells that may contribute to
      the unresponsiveness seen in patients with sepsis.

PMID- 16785566
TI  - Conserved nontypeable Haemophilus influenzae-derived TLR2-binding lipopeptides
      synergize with IFN-beta to increase cytokine production by resident murine and
      human alveolar macrophages.
AB  - Nontypeable Haemophilus influenzae (NTHi) is strongly associated with
      exacerbations of chronic obstructive pulmonary disease, which often coincide with
      viral respiratory infections. TLR2 contributes importantly to innate immunity to
      NTHi, but whether this pathway is affected by simultaneous antiviral responses is
      unknown. To analyze potential interactions, resident murine and human alveolar
      macrophages (AMphi) were exposed, in the presence or absence of the appropriate
      rIFN-beta, to synthetic lipopeptides corresponding to the triacylated N-terminal
      fragments of three outer membrane proteins (OMP) (PCP, P4, and P6) that are
      highly conserved among different NTHi strains. Synthetic OMP elicited strong
      release of IL-6, the principal inducer of airway mucin genes, and induced CCL5
      and CXCL10 from murine AMphi only when IFN-beta was also present. Surprisingly,
      combined stimulation by OMPs and IFN-beta also markedly enhanced TNF-alpha
      release by murine AMphi. Stimulation with PCP plus IFN-beta induced IFN
      regulatory factor 1 expression and sustained STAT1 activation, but did not alter
      the activation of MAPKs or NF-kappaB. AMphi derived from STAT1-deficient mice did
      not demonstrate increased production of TNF-alpha in response to PCP plus IFN
      beta. Analysis of wild-type and STAT1-deficient AMphi using real-time PCR showed
      that increased TNF-alpha production depended on transcriptional up-regulation,
      but not on mRNA stabilization. The synergistic effect of synthetic OMP and IFN
      beta was conserved between murine AMphi and human AMphi for IL-6, but not for TNF
      alpha. Thus, IFN-beta, which is produced by virally infected respiratory
      epithelial cells, converts normally innocuous NTHi OMP into potent inflammatory
      stimulants, but does so via different mechanisms in mice and humans.

PMID- 16785567
TI  - Peptidoglycan-induced IL-6 production in RAW 264.7 macrophages is mediated by
      cyclooxygenase-2, PGE2/PGE4 receptors, protein kinase A, I kappa B kinase, and NF
      kappa B.
AB  - In this study, we investigated the signaling pathway involved in IL-6 production
      caused by peptidoglycan (PGN), a cell wall component of the Gram-positive
      bacterium, Staphylococcus aureus, in RAW 264.7 macrophages. PGN caused
      concentration- and time-dependent increases in IL-6, PGE(2), and cAMP production.
      PGN-mediated IL-6 production was inhibited by a nonselective cyclooxygenase (COX)
      inhibitor (indomethacin), a selective COX-2 inhibitor (NS398), a PGE(2) (EP2)
      antagonist (AH6809), a PGE(4) (EP4) antagonist (AH23848), and a protein kinase A
      (PKA) inhibitor (KT5720), but not by a nonselective NO synthase inhibitor (N(G)
      nitro-l-arginine methyl ester). Furthermore, PGE(2), an EP2 agonist (butaprost),
      an EP2/PGE(3) (EP3)/EP4 agonist (misoprostol), and misoprostol in the presence of
      AH6809 all induced IL-6 production, whereas an EP1/EP3 agonist (sulprostone) did
      not. PGN caused time-dependent activations of IkappaB kinase alphabeta (IKKdbeta)
      and p65 phosphorylation at Ser(276), and these effects were inhibited by NS398
      and KT5720. Both PGE(2) and 8-bromo-cAMP also caused IKKdbeta kinase alphabeta
      phosphorylation. PGN resulted in two waves of the formation of NF-kappaB-specific
      DNA-protein complexes. The first wave of NF-kappaB activation occurred at 10-60
      min of treatment, whereas the later wave occurred at 2-12 h of treatment. The PGN
      induced increase in kappaB luciferase activity was inhibited by NS398, AH6809,
      AH23848, KT5720, a protein kinase C inhibitor (Ro31-8220), and a p38 MAPK
      inhibitor (SB203580). These results suggest that PGN-induced IL-6 production
      involves COX-2-generated PGE(2), activation of the EP2 and EP4 receptors, cAMP
      formation, and the activation of PKA, protein kinase C, p38 MAPK, IKKdbeta,
      kinase alphabeta, p65 phosphorylation, and NF-kappaB. However, PGN-induced NO
      release is not involved in the signaling pathway of PGN-induced IL-6 production.

PMID- 16785568
TI  - Fc gamma RIIa, not Fc gamma RIIb, is constitutively and functionally expressed on
      skin-derived human mast cells.
AB  - The expression of FcgammaR by human skin-derived mast cells of the MC(TC) type
      was determined in the current study. Expression of mRNA was analyzed with
      microarray gene chips and RT-PCR; protein by Western blotting and flow cytometry;
      function by release of beta-hexosaminidase, PGD(2), leukotriene C(4) (LTC(4)), IL
      5, IL-6, IL-13, GM-CSF, and TNF-alpha. FcgammaRIIa was consistently detected
      along with FcepsilonRI at the mRNA and protein levels; FcgammaRIIc was sometimes
      detected only by RT-PCR; but FcgammaRIIb, FcgammaRI, and FcgammaRIII mRNA and
      protein were not detected. FcgammaRIIa-specific mAb caused skin MC(TC) cells to
      degranulate and secrete PGD(2), LTC(4), GM-CSF, IL-5, IL-6, IL-13, and TNF-alpha
      in a dose-dependent fashion. FcepsilonRI-specific mAb caused similar amounts of
      each mediator to be released with the exception of LTC(4), which was not released
      by this agonist. Simultaneous but independent cross-linking of FcepsilonRI and
      FcgammaRIIa did not substantially alter mediator release above or below levels
      observed with each agent alone. Skin MC(TC) cells sensitized with dust-mite
      specific IgE and IgG, when coaggregated by Der p2, exhibited enhanced
      degranulation compared with sensitization with either IgE or IgG alone. These
      results extend the known capabilities of human skin mast cells to respond to IgG
      as well as IgE-mediated signals.

PMID- 16785569
TI  - Inhibition of mixed lineage kinase 3 prevents HIV-1 Tat-mediated neurotoxicity
      and monocyte activation.
AB  - The HIV-1 gene products Tat and gp120 are toxic to neurons and can activate cells
      of myeloid origin, properties that are thought to contribute to the clinical
      manifestations of HIV-1-associated dementia (HAD). To investigate the
      intracellular signaling mechanisms involved in these events, the effect of Tat
      and gp120 on mixed lineage kinase (MLK) 3 activation was examined. Tat and gp120
      were shown to induce autophosphorylation of MLK3 in primary rat neurons; this was
      abolished by the addition of an inhibitor of MLK3 (CEP1347). CEP1347 also
      enhanced survival of both rat and human neurons and inhibited the activation of
      human monocytes after exposure to Tat and gp120. Furthermore, overexpression of
      wild-type MLK3 led to the induction of neuronal death, whereas expression of a
      dominant negative MLK3 mutant protected neurons from the toxic effects of Tat.
      MLK3-dependent downstream signaling events were implicated in the neuroprotective
      and monocyte-deactivating pathways triggered by CEP1347. Thus, the inhibition of
      p38 MAPK and JNK protected neurons from Tat-induced apoptosis, whereas the
      inhibition of p38 MAPK, but not of JNK, was sufficient to prevent Tat- and gp120
      mediated activation of monocytes. These results suggest that the normal function
      of MLK3 is compromised by HIV-1 neurotoxins (Tat, gp120), resulting in the
      activation of downstream signaling events that result in neuronal death and
      monocyte activation (with release of inflammatory cytokines). In aggregate, our
      data define MLK3 as a promising therapeutic target for intervention in HAD.

PMID- 16785571
TI  - Homozygosity for the IgG2 subclass allotype G2M(n) protects against severe
      infection in hereditary C2 deficiency.
AB  - Homozygous C2 deficiency (C2D) is the most common deficiency of the classical
      complement pathway in Western countries. It is mostly found in patients with
      autoimmune disease or susceptibility to bacterial infections and in healthy
      persons. We wished to assess to what extent other immunological factors might
      explain differences of susceptibility to infections in C2D. For this reason, 44
      Swedish patients with C2D were stratified with regard to the severity of
      documented infections. Investigations of IgG subclass levels, IgG subclass
      specific GM allotypes, concentrations of factor B, properdin, and factor H, and
      polymorphisms of mannan-binding lectin and the Fc receptors FcgammaRIIa and
      FcgammaRIIIb were performed. Homozygosity for the G2M*n allele, which is known to
      promote Ab responses to polysaccharide Ags, was strongly associated with the
      absence of severe infections (p < 0.001) in the patients, suggesting a major
      protective role. The combination of mannan (or mannose)-binding lectin and C2
      deficiency was found to be a minor susceptibility factor for invasive infection
      (p = 0.03). Low concentrations of IgG2 and factor B might sometimes contribute to
      susceptibility to infection. Other factors investigated did not appear to be
      important. In conclusion, the findings indicated that efficient Ab responses to
      polysaccharides are protective against severe infection in C2D. Implications with
      regard to vaccination should be considered.

PMID- 16785570
TI  - Hierarchy of alpha fetoprotein (AFP)-specific T cell responses in subjects with
      AFP-positive hepatocellular cancer.
AB  - We identified a series of immunodominant and subdominant epitopes from alpha
      fetoprotein (AFP), restricted by HLA-A*0201, which are recognized by the human T
      cell repertoire. The four immunodominant epitopes have been tested for
      immunogenicity in vivo, in HLA-A*0201+AFP+ advanced stage hepatocellular cancer
      (HCC) patients, and have activated and expanded AFP-specific IFN-gamma-producing
      T cells in these patients, despite high serum levels of this self Ag. Here, we
      have examined the frequency, function, and avidity of the T cells specific for
      subdominant epitopes from AFP. We find that T cells specific for several of these
      epitopes are of similar or higher avidity than those specific for immunodominant
      epitopes. We then tested the peripheral blood of subjects ex vivo with different
      levels of serum AFP for the hierarchy of response to epitopes from this Ag and
      find that HCC patients have detectable frequencies of circulating IFN-gamma
      producing AFP-specific CD8+ T cells to both immunodominant and subdominant
      epitopes. We find the immunodominant and subdominant peptide-specific T cells to
      be differentially expanded with different modes of Ag presentation. Whereas
      spontaneous and AFP protein-stimulated responses show evidence for
      immunodominance, AdVhAFP-transduced dendritic cell-stimulated responses were
      broader and not skewed. Importantly, these data identify subdominant epitopes
      from AFP that can activate high-avidity T cells, and that can be detected and
      expanded in HCC subjects. These subdominant epitope-specific T cells can also
      recognize tumor cells and may be important therapeutically.

PMID- 16785572
TI  - Detailed analysis of intrahepatic CD8 T cells in the normal and hepatitis C
      infected liver reveals differences in specific populations of memory cells with
      distinct homing phenotypes.
AB  - In hepatitis C virus (HCV) infection the immune response is ineffective, leading
      to chronic hepatitis and liver damage. Primed CD8 T cells are critical for
      antiviral immunity and subsets of circulating CD8 T cells have been defined in
      blood but these do not necessarily reflect the clonality or differentiation of
      cells within tissue. Current models divide primed CD8 T cells into effector and
      memory cells, further subdivided into central memory (CCR7+, L-selectin+),
      recirculating through lymphoid tissues and effector memory (CCR7-, L-selectin-)
      mediating immune response in peripheral organs. We characterized CD8 T cells
      derived from organ donors and patients with end-stage HCV infection to show that:
      1) all liver-infiltrating CD8 T cells express high levels of CD11a, indicating
      the effective absence of naive CD8 T cells in the liver. 2) The liver contains
      distinct subsets of primed CD8+ T cells including a population of CCR7+ L
      selectin- cells, which does not reflect current paradigms. The expression of CCR7
      by these cells may be induced by the hepatic microenvironment to facilitate
      recirculation. 3) The CCR7 ligands CCL19 and CCL21 are present on lymphatic,
      vascular, and sinusoidal endothelium in normal liver and in patients with HCV
      infection. We suggest that the recirculation of CCR7+/L-selectin- intrahepatic
      CD8 T cells to regional lymphoid tissue will be facilitated by CCL19 and CCL21 on
      hepatic sinusoids and lymphatics. This centripetal pathway of migration would
      allow restimulation in lymph nodes, thereby promoting immune surveillance in
      normal liver and renewal of effector responses in chronic viral infection.

PMID- 16785573
TI  - Circulating and liver resident CD4+CD25+ regulatory T cells actively influence
      the antiviral immune response and disease progression in patients with hepatitis
      B.
AB  - CD4+CD25+ regulatory T cells (Treg) have been shown to maintain immune tolerance
      against self and foreign Ags, but their role in persistent viral infection has
      not been well-defined. In this study, we investigated whether and where CD4+CD25+
      Treg contribute to the development of chronic hepatitis B (CHB). One hundred
      twenty-one patients were enrolled, including 16 patients with acute hepatitis B,
      76 with CHB, and 29 with chronic severe hepatitis B. We demonstrated that in
      chronic severe hepatitis B patients, the frequencies of CD4+CD25+ Treg in both
      PBMC and liver-infiltrating lymphocytes were significantly increased and there
      was a dramatic increase of FoxP3(+)-cell and inflammatory cell infiltration in
      the liver compared with healthy controls. In CHB patients, circulating CD4+CD25+
      Treg frequency significantly correlates with serum viral load. In acute hepatitis
      B patients, circulating CD4+CD25+ Treg frequency was initially low and with time,
      the profile reversed to exhibit an increased number of circulating Treg in the
      convalescent phase and restored to normal levels upon resolution. In PBMC taken
      from infected patients, depletion of CD4+CD25+ Treg led to an increase of IFN
      gamma production by HBV-Ag-stimulated PBMC. In addition, CD4+CD25+ Treg were
      capable of suppressing proliferation of autologous PBMC mediated by HBV Ags,
      which probably reflects the generation of HBV-Ag-specific Treg in circulation and
      in the liver of HBV-infected patients. Together, our findings suggest that
      CD4+CD25+ Treg play an active role not only in modulating effectors of immune
      response to HBV infection, but also in influencing the disease prognosis in
      patients with hepatitis B.

PMID- 16785575
TI  - Six days in Charity Hospital: two doctors' ordeal in Hurricane Katrina.
AB  - Hurricane Katrina devastated the city of New Orleans as well as a large section
      of the Gulf Coastal region of the United States. Herein, we present a first-hand
      view of physicians who were actually running the hospital of a major medical
      center during this natural disaster. This event demonstrates the vulnerability of
      basic human services, including health care even in industrialized, wealthy
      countries.

PMID- 16785576
TI  - Hereditary hemochromatosis: a review of the genetics, mechanism, diagnosis, and
      treatment of iron overload.
AB  - Hereditary hemochromatosis is a relatively common genetic disorder characterized
      by excess dietary iron absorption and deposition in tissues with resulting end
      organ damage. Early diagnosis and initiation of therapeutic phlebotomy can
      provide a normal life expectancy for affected individuals.

PMID- 16785577
TI  - Lyme disease: questions and discussion.
AB  - Diagnosis of Lyme disease is problematic and results in both overtreatment and
      mistreatment. Attention to epidemiology and physical findings will prevent
      inappropriate investigations and therapies. The disease has tropisms for specific
      tissues, and medical care should be tailored to the site and severity of
      infection.

PMID- 16785578
TI  - High-risk stress fractures: pathogenesis, evaluation, and treatment.
AB  - High-risk stress fractures require precise assessment and treatment because of
      their propensity for delayed union, nonunion, or complete fracture and their
      resulting disabling complications. Proper diagnosis necessitates a thorough
      clinical evaluation, centering on the patient's diet and history, particularly
      the training regimen. For a definitive diagnosis, plain radiography, ultrasound,
      bone scintigraphy, magnetic resonance imagery (MRI), and computed tomography (CT)
      are helpful, and each plays a specific role. High-risk stress fractures typically
      require aggressive treatment such as nonweight-bearing immobilization coupled
      with therapy and often surgery.

PMID- 16785579
TI  - Bupropion for smoking cessation: a review.
AB  - Smoking tobacco is the leading cause of preventable death. Bupropion is the only
      antidepressant recommended as first-line pharmacotherapy for smoking cessation.
      Bupropion is as effective as nicotine replacement therapy and can be used in
      diverse populations.

PMID- 16785580
TI  - Outcomes, health status, and medical resource utilization after bariatric
      surgery.
AB  - Surgical results, economic consequences, and shortterm health of obese patients
      were evaluated before and after bariatric surgery. Of 35 patients in Mayo Health
      Plan Arizona eligible for bariatric surgery and scheduled for gastric restriction
      with Roux-en-Y gastrojejunostomy, 22 (7 men, 15 women) completed pre- and
      postoperative (6- and 12-mo) short form (SF)-12 Health Surveys. Nineteen patients
      had open bariatric procedures and 3 had laparoscopic procedures. Comorbid
      conditions, hospital course, weight loss, and complications were examined. Health
      care utilization (actual dollars paid by plan) for the preceding year and at 1-
      and 2-yr follow-up were compared. Major comorbid conditions included diabetes
      mellitus or impaired fasting glucose, hyperlipidemia, sleep apnea, and
      hypertension. Mean length of hospital stay was 4.8 d after open procedures and 2
      d after laparoscopic procedures. No serious operative or postoperative
      complications occurred. From a baseline average body mass index (BMI) of 51.9,
      the 6- and 12-mo BMI averages were 39.6 (23.7% decrease) and 35.3 (32% decrease),
      respectively. Both physical and mental status improved. From baseline, physical
      health changed 18 and 21.2 points at 6 and 12 mo, respectively (p < 0.001), and
      mental health changed 9.3 points at each interval (p =0.003). Each postoperative
      year, resource utilization decreased (mean= $1300 per patient). Our findings of
      good surgical outcomes, significant weight loss, improved health status, and
      potential financial savings in this small sample may help patients, insurers, and
      self-funded employer groups evaluate the appropriateness of bariatric procedures.

PMID- 16785581
TI  - Treating the victims after disaster: physical and psychological effects.
AB  - Disaster victims present in waves. The initial presenting group is traditionally
      suffering from mild physical injuries, and the second wave, usually following 6 h
      later, typically has more serious trauma. Medical problems typically are not
      adequately treated when a person has psychological reasons to worry about
      survival. The third wave of victims from untreated medical problems occurs 6 d
      after the initial disaster. Triage of the initial waves is important to prevent
      the system from becoming overwhelmed and to begin looking for those who will
      suffer long-term psychological sequelae. Early intervention in those at greatest
      risk for long-term issues is important and can be accomplished.

PMID- 16785582
TI  - The red eye.
AB  - A red eye is a cardinal sign of ocular inflammation. Most cases are benign and
      can be managed by the primary care provider. The key is recognizing cases
      requiring ophthalmological consultation by differentiating between ciliary and
      conjunctival injection. Ciliary injection indicates inflammation of the cornea,
      iris, or ciliary body, whereas conjunctival injection mainly affects the
      posterior conjunctival blood vessels.

PMID- 16785583
TI  - Carbohydrate and calories: it is not what we used to think.
AB  - The majority of our diet consists of carbohydrates. Carbohydrates may be
      glycemic, which can be broken down and turned into simple glucose molecules
      quickly, or non-glycemic, which are not turned into sugar until they reach the
      large intestine. The glycemic index tells us how quickly the food we eat is
      turned into sugar and the glycemic load will give us absolute amounts of sugar
      introduced into the body by a food. Processing of foods and addition of fructose
      to the diet are major changes that correlate with weight gain in individuals.
      Decreasing carbohydrates in the diet goes along with a decrease in total calories
      in the diet.

PMID- 16785584
TI  - The importance of recognizing postural pseudoanemia.
AB  - The determination of the packed red cell volume and the hemoglobin level has been
      paramount for monitoring anemia and blood loss for patients in the hospital
      setting. Recently, these variables have been studied during various control
      conditions including changes in posture. It has been found that the hematocrit
      changes markedly with alteration of body posture, in such a way that shifts of
      estimated blood volume of 1 pint can commonly be elicited by a simple change of
      posture from supine to upright or vice versa. Therefore, it is important to
      recognize that in addition to the numerous pathological conditions that may
      affect the value of the packed cell volume, certain physiological maneuvers may
      have an equal impact and may confound the accurate assessment of true
      pathological changes in these variables. Thus, changes in posture can lead to
      substantial changes in hematocrit, which may be attributed mistakenly to blood
      loss or acute anemia and may result in a cascade of unnecessary diagnostic costs.
      In reality, these changes represent postural pseudoanemia, a normal physiological
      response to a change in position from standing to lying.

PMID- 16785586
TI  - Beginning antibiotics for acute rhinosinusitis and choosing the right treatment.
AB  - Acute bacterial sinusitis (ABS) is an extremely common problem in both children
      and adults. There are three clinical presentations of acute sinusitis: (1) onset
      with persistent symptoms (nasal symptoms or cough or both for > 10 but < 30 d
      without evidence of improvement); (2) onset with severe symptoms (high fever and
      purulent nasal discharge for 3-4 consecutive days); and (3) onset with worsening
      symptoms (respiratory symptoms, with or without fever, which worsen after several
      days of improvement). Images to confirm the presence of acute sinusitis are
      necessary in older children (> 6 years) and adults to enhance the certainty of
      diagnosis. The predominant bacterial species that are implicated in acute
      sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
      catarrhalis in children. In the last decade, there has been an increasing
      prevalence of penicillin-resistant S. pneumoniae, and beta-lactamase-producing H.
      influenzae and M. catarrhalis. Although there has been some controversy in the
      literature regarding the effectiveness of antibiotics in the treatment of ABS,
      most studies in which the diagnosis of acute bacterial sinusitis is confirmed
      with images and appropriate anti-biotics are prescribed show superior outcomes in
      recipients of antibiotics. Therapy may be initiated with high-dose amoxicillin or
      amoxicillin-clavulanate. In penicillin-allergic patients or those who are
      unresponsive to amoxicillin, amoxicillin-clavulanate is appropriate. Alternatives
      include cefuroxime, cefpodoxime, or cefdinir. In cases of serious drug allergy,
      clarithromycin or azithromycin may be prescribed. The optimal duration of therapy
      is unknown. Some recommend treatment until the patient becomes free of symptoms
      and then for an additional 7 d.

PMID- 16785587
TI  - Is rhinosinusitis a cause of asthma?
AB  - There is a great deal of evidence of an association between rhinosinusitis and
      asthma. However, it is less clear whether rhinosinusitis is a direct trigger for
      asthma or the two conditions are simply manifestations of a common underlying
      process. Evidence for a role for rhinosinusitis as a trigger for asthma includes
      many examples of improvement in asthma once concomitant rhinosinusitis is treated
      medically or surgically. Possible mechanisms for this relationship include naso
      pharyngo-bronchial reflexes, postnasal drip, abnormal breathing, and the local
      production of inflammatory mediators that trigger pulmonary inflammation via the
      bone marrow. On the other hand, evidence exists that rhinosinusitis and asthma
      are manifestations of a common process. For example, there are similarities
      between the histopathological changes in the epithelium in chronic rhinosinusitis
      and asthma. The bone marrow may provide the link between the upper and lower
      airways in creating a common disease. A second possible mechanism for a common
      disease is response to staphylococcal enterotoxins. Although evidence exists to
      suggest that rhinosinusitis either triggers asthma or represents a local
      manifestation of a shared disorder, the key to reconciling this apparent
      controversy is to consider that rhinosinusitis is not just a single, uniform
      disease. Current evidence suggests that rhinosinusitis with neither polyps nor
      eosinophilic inflammation acts as a direct trigger for asthma, whereas
      rhinosinusitis with both polyps and eosinophilic inflammation shares underlying
      mechanisms with asthma. Clearly, however, there is considerable overlap between
      the different, complex mechanisms that link rhinosinusitis to asthma.

PMID- 16785588
TI  - Imaging of rhinosinusitis and its complications: plain film, CT, and MRI.
AB  - Conventional plain-film radiography may be used as a screening method for various
      pathological conditions of the sinonasal cavities. However, CT scanning remains
      the study of choice for the imaging evaluation of acute and chronic inflammatory
      diseases of sinonasal cavities. MRI is superior to CT in differentiating
      inflammatory conditions from neoplastic processes. The most common complications
      of rhinosinusitis in children occur in the orbit. The information obtained from
      the CT scan and MRI, together with clinical findings, may be the best guidelines
      for clinical management and the mode of treatment. Although intracranial
      complications of sinusitis are relatively rare, prompt recognition of these
      disease states is important to prevent permanent neurological deficit or
      fatality. It is prudent to obtain MRI of the sinuses, orbits, and brain whenever
      extensive or multiple complications of sinusitis are suspected, in addition to CT
      scanning. Chronic rhinosinusitis is a clinical diagnosis, confirmed and staged
      with the CT scan of sinonasal cavities. Chronic inflammatory disease is often
      associated with mucosal thickening and sclerosis of the bone, particularly within
      the sinuses. Chronic extramucosal fungal sinusitis develops as a saprophytic
      growth in retained secretions in a sinus cavity. The imaging manifestations of
      chronic mycotic rhinosinusitis may be nonspecific or highly suggestive of the
      presence of fungal infection. The presence of diffuse increased attenuation
      within the paranasal sinuses and nasal cavity should be considered as chronic
      allergic hypersensitivity aspergillosis (chronic noninvasive aspergillosis) or
      chronic hyperplastic sinusitis and polyposis associated with desiccated, retained
      mucosal secretions. The MRI characteristics of fungal sinusitis depend on the
      stage of the disease.

PMID- 16785589
TI  - The role of ubiquitous airborne fungi in chronic rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is a confusing disease for both allergists and
      otorhinolaryngologists, partly because of its poorly understood pathophysiology
      and partly because of its limited treatment options. Several recent reports have
      provided evidence for a better understanding of the etiology and the relationship
      of CRS to airborne fungi-especially to Alternaria. First, the development of
      novel methods enables detection of certain fungi in mucus from the nasal and
      paranasal sinus cavities. Second, a non-IgE-mediated immunological mechanism for
      reactivity of patients with CRS to certain common fungi has been described.
      Third, these fungi are surrounded by eosinophils in vivo, suggesting that they
      are targeted by eosinophils. Finally, the preliminary results of studies using
      antifungal agents to treat patients with CRS are promising. Overall, these recent
      discoveries provide a logical mechanism for the pathophysiology of CRS, and they
      also suggest promising avenues for treatment of CRS with antifungal agents.

PMID- 16785590
TI  - Fungi in chronic hyperplastic eosinophilic sinusitis: reasonable doubt.
AB  - Chronic hyperplastic eosinophilic sinusitis (CHES) is a T-helper (Th)2-like,
      lymphocyteinitiated, eosinophil-rich inflammatory disease. The complex immune
      interactions required to orchestrate these processes begin with the presentation
      of antigen by mature dendritic cells to Th lymphocytes that display the
      appropriate antigen-specific T-cell receptor. The objective of sinus research
      must be to identify and target that antigen; this will lead to the cure for this
      condition. This article reviews numerous models that may be responsible for the
      pathophysiology of this disorder, including putative roles for allergens,
      bacteria, and bacterial-derived superantigens, as well as recent interest in
      fungal-derived antigens. Additionally, we speculate that whatever the inciting
      cause of CHES may be, it is plausible that once initiated, cellular
      differentiation pathways may lead to the development of an antigen-independent
      permanent phase. More than one of these may be valid in different subjects and,
      furthermore, this list almost assuredly does not explain all cases of CHES. The
      concept that fungal antigens colonizing the sinuses are responsible for CHES
      represents an intriguing, but unproven, hypothesis. Presently, the case for the
      fungus remains circumstantial. The case for fungi will be proved only with
      definitive proof that T-cells within the sinuses are actively responding to
      fungal antigens present in the sinus and with the further demonstration that
      removal of those fungal antigens ameliorates the disease.

PMID- 16785592
TI  - Sinus surgery: indications and techniques.
AB  - Functional endoscopic sinus surgery (FESS) is a recent addition to the treatment
      armamentarium of sinus disease. Performed through the nasal cavity using
      endoscopes and inciting no external scars, these advantages have renewed an
      interest in the surgical intervention of various sinus diseases. With minimal
      risk and complications associated with FESS, the temptation exists to lower the
      threshold and expand the indications for sinus surgery. However, regardless of
      the reduced risk, FESS should be pursued only when the goals are attainable and
      the limitations of surgery are understood for each specific disease. Chronic
      rhinosinusitis (CRS), affecting more than 31 million people a year, represents a
      treatment challenge. The challenge stems from evidence that CRS can result from
      different etiologies including bacteria, virus, fungi, superantigens, and
      unfavorable anatomy. With an unclear pathogenesis, success of medical therapy is
      often limited. Individuals failing medical therapy are candidates for surgical
      intervention. The controversy, indications, and goals of surgery in CRS are
      reviewed. Other indications for FESS are less controversial. Nasal polyps, which
      can interfere with medical therapy and obstruct airflow, often require surgical
      intervention. In addition, recent data has suggested a link between surgery and a
      reduction in inflammatory markers. Repair of skull base defects, and resection of
      benign and limited malignant nasal masses are also indications for FESS. This
      article reviews the indications of sinus surgery. In addition, it addresses some
      of the controversies, limitations, and advances in FESS.

PMID- 16785591
TI  - Allergic fungal sinusitis.
AB  - Many common chronic inflammatory rhinosinusitis conditions (hypertrophic sinus
      disease [HSD]) have the histopathological profile of allergic or asthmatic
      inflammation. Allergic fungal sinusitis (AFS) is both a type of noninvasive
      fungal rhinosinusitis and a type of HSD. AFS has clinicopathological features
      that make it similar, but not identical, to allergic bronchopulmonary
      aspergillosis (ABPA). Allergic mucin is a defined pathological entity occurring
      in ABPA, AFS, and in the HSD "eosinophilic mucin rhinosinusitis (EMRS)."
      Diagnosis of AFS requires a careful review of surgical reports, histopathology,
      and culture results. Treatment includes surgery and aggressive postoperative
      medical management of allergic inflammatory disease. Prognosis is good with
      integrated medical-surgical follow-up, but recurrence remains problematic. The
      association of ABPA, AFS, and HSD with class II genes of the major
      histocompatibility complex places the initiation of these inflammatory diseases
      within the context of antigen presentation and the acquired immune response.
      Pathological immunomanipulation of this response by local microbial superantigens
      may be a common mechanism for disease pathogenesis. Future research into the
      molecular biology of these related conditions may offer insight into the
      pathogenesis of other chronic inflammatory diseases.

PMID- 16785594
TI  - Estrogen effects on neuronal morphology.
AB  - This review focuses on the effects of estrogen on neuronal morphology. Over the
      last decade neuroscientists have accumulated a wealth of information confirming
      the trophic effects of 17beta-estradiol on a variety of brain regions, including
      changes of hippocampal spine density and axonal outgrowth and retraction in
      hypothalamic nuclei, as well as other measures of structural reorganization that
      could underlie some of the cognitive benefits attributed to this hormone.
      Overall, results from a variety of investigators suggest that 17beta-estradiol is
      a potent structural signal that can drive developmental as well as adult plastic
      events in a variety of brain regions, not only those implicated in reproduction,
      but also in a diversity of functions. Most notably, these structural
      modifications that subserve cyclic physiological processes, can also be activated
      in other brain regions to protect and even reverse structural neurodegenerative
      processes. The data presented here are not exhaustive, but rather meant to
      provide a few examples of these structural effects of 17beta-estradiol that could
      have important implications for clinical practice.

PMID- 16785595
TI  - Age-related changes in neuroprotection: is estrogen pro-inflammatory for the
      reproductive senescent brain?
AB  - Estrogen replacement therapy (ERT) is widely prescribed to postmenopausal women
      for relief from the adverse vasomotor effects of menopause, to reduce bone loss,
      to improve cardiovascular health, and to protect against metabolic disorders.
      However, there is now greater awareness of the increased risk to benefit ratio
      from the recently concluded Women's Health Initiative Memory Study (WHIMS), which
      reported that ERT increased the risk of cognitive impairment and dementia in
      elderly women. Studies from the experimental literature indicate that while
      estrogen is neuroprotective in many instances, estrogen replacement can be
      deleterious in some cases. These differences may be partly due to the age and
      species of the experimental model. The majority of the experimental data comes
      from studies where the age or endocrine status of the animal model is not
      comparable to that of menopausal or postmenopausal women, such as those in the
      WHIMS study. In this review, we will focus on age-related changes in estrogen's
      neuroprotective effects and evidence that reproductive senescence-related changes
      in the blood-brain barrier and the immune system may result in deleterious
      consequences for ERT.

PMID- 16785597
TI  - Mechanisms of neuroprotection by estrogen.
AB  - Over the past decade our recognition that estrogens function as important
      neurotrophic and neuroprotective factors has grown rapidly. Accumulating evidence
      from basic science studies demonstrates that estrogens exert profound protective
      actions against various forms of neurodegenerative diseases and injury. Although
      a thorough understanding of the mechanisms underlying the protective effect of
      estrogens is far from complete, significant progress has been achieved through
      the use of in vivo as well as in vitro models. Here we review the results from
      our laboratory demonstrating that low physiological levels of estradiol therapy
      exert powerful protection against ischemic stroke-like injury. Using an animal
      model of cerebrovascular stroke and in vitro explant cultures, we have begun to
      decipher under what circumstances 17beta-estradiol protects against neuronal
      death and to uncover its mechanisms of action. In addition, we will review recent
      work demonstrating that estradiol may additionally enhance the ability of the
      adult brain to undergo repair by influencing the production of new neurons under
      neuropathological conditions, as well as by promoting an anti-inflammatory
      response. As we uncover the important protective roles of ovarian steroid
      hormones in brain disease and injury, we increasingly appreciate that the
      mechanisms by which estrogens achieve these effects are diverse and complex.

PMID- 16785596
TI  - Multiple pathways transmit neuroprotective effects of gonadal steroids.
AB  - Numerous preclinical studies suggest that gonadal steroids, particularly
      estrogen, may be neuroprotective against insult or disease progression. This
      paper reviews the mechanisms contributing to estrogen-mediated neuroprotection.
      Rapid signaling pathways, such as MAPK, PI3K, Akt, and PKC, are required for
      estrogen's ability to provide neuroprotection. These rapid signaling pathways
      converge on genomic pathways to modulate transcription of E2-responsive genes via
      ERE-dependent and ERE-independent mechanisms. It is clear that both rapid
      signaling and transcription are important for estrogen's neuroprotective effects.
      A mechanistic understanding of estrogen-mediated neuroprotection is crucial for
      the development of therapeutic interventions that enhance quality of life without
      deleterious side effects.

PMID- 16785598
TI  - Neuroprotection by ovarian hormones in animal models of neurological disease.
AB  - Ovarian hormones can protect against brain injury, neurodegeneration, and
      cognitive decline. Most attention has focused on estrogens and accumulating data
      demonstrate that estrogen seems to specifically protect cortical and hippocampal
      neurons from ischemic injury and from damage due to severe seizures. Although
      multiple studies demonstrate protection by estrogen, in only a few instances is
      the issue of how the steroid confers protection known. Here, we first review data
      evaluating the neuroprotective effects of estrogens, a selective estrogen
      receptor modulator (SERM), and estrogen receptor alpha- and beta-selective
      ligands in animal models of focal and global ischemia. Using focal ischemia in
      ovariectomized ERalphaKO, ERbetaKO, and wild-type mice, we clearly established
      that the ERalpha subtype is the critical ER mediating neuroprotection in mouse
      focal ischemia. In rats and mice, the middle cerebral artery occlusion (MCAO)
      model was used to represent cerebrovascular stroke, while in gerbils the two
      vessel occlusion model, representing global ischemia, was used. The gerbil global
      ischemia model was used to evaluate the neuroprotective effects of estrogen,
      SERMs, and ERalpha- and ERbeta-selective compounds in the hippocampus. Analysis
      of neurogranin mRNA, a marker of viability of hippocampal neurons, with in situ
      hybridization, revealed that estrogen treatment protected the dorsal CA1 regions
      not only when administered before, but also when given 1 h after occlusion.
      Estrogen rarely is secreted alone and studies of neuroprotection have been less
      extensive for a second key ovarian hormone progesterone. In the second half of
      this review, we present data on neuroprotection by estrogen and progesterone in
      animal model of epilepsy followed by exploration into ovarian steroid effects on
      neuronal damage in models of multiple sclerosis and traumatic brain injury.

PMID- 16785599
TI  - Androgens, aging, and Alzheimer's disease.
AB  - Testosterone depletion is a normal consequence of aging in men that is associated
      with senescent effects in androgen- responsive tissues. We discuss new evidence
      that one consequence of testosterone depletion in men is an increased risk for
      the development of Alzheimer's disease (AD). Furthermore, we discuss two
      candidate mechanisms by which testosterone may affect AD pathogenesis. First,
      testosterone has been identified as an endogenous regulator of beta-amyloid, a
      protein that abnormally accumulates in AD brain and is implicated as a causal
      factor in the disease. Second, findings from several different paradigms indicate
      that testosterone has both neurotrophic and neuroprotective functions. These new
      findings support the clinical evaluation of androgen-based therapies for the
      prevention and treatment of AD.

PMID- 16785602
TI  - Progesterone-induced neuroprotection.
AB  - Estrogen and progesterone are two steroid hormones whose biology has been greatly
      studied within the confines of reproductive function. As a consequence, the
      effects of these hormones on the brain have focused primarily on the
      hypothalamus. Growing evidence, however, forces us to recognize that various
      extrahypothalamic brain regions, including the cerebral cortex and hippocampus,
      are equally important targets of these hormones. As such, hormones are involved
      in numerous aspects of brain function, and elicit effects ranging from the
      regulation of mood and cognition to the regulation of neuronal survival. While
      estrogen exerts neuroprotective effects in various experimental models, the
      potential for progesterone as a protective agent has, until recently, been
      greatly understudied. Here, we review the data from various laboratories
      including our own that support the protective role of progesterone and describe
      the multiplicity of mechanisms by which progesterone elicits these protective
      effects. Finally, we contrast the neurobiology of progesterone with that of the
      clinically used progestin, medroxyprogesterone acetate (MPA), and suggest that
      the "natural" progesterone may be the better choice when considering which
      progestin to use for future therapeutic/ palliative purposes in CNS-related
      disorders.

PMID- 16785601
TI  - The role of gonadotropins in Alzheimer's disease: potential neurodegenerative
      mechanisms.
AB  - In addition to the classical role of gonadotropins as a modulator of sex hormone
      production, it is now becoming apparent that the gonadotropins may have actions
      within the central nervous system. Evidence is also mounting that age-related
      increases in levels of the gonadotropin, luteinizing hormone (LH), may exert
      neurodegenerative effects such as those seen in Alzheimer's disease (AD). LH has
      been implicated in key cellular and biochemical processes that contribute to the
      pathogenesis of AD. These processes include the altered metabolism of key
      proteins in AD pathology, beta amyloid (Abeta), and its parent molecule, the
      amyloid precursor protein (APP). Evidence in the literature suggests that
      gonadotropins may be involved in processes that contribute to the
      etiology/pathogenesis of AD such as inflammation, cholesterol homeostasis, and
      insulin status. Here we examine the potential mechanisms by which gonadotropins
      could influence neurodegenerative processes. The role of gonadotropins in the
      brain and potential direct neuropathological effects of elevated gonadotropin
      levels is an exciting new topic in neuroendocrinology that in turn will lead to
      the development of novel therapeutic approaches for AD.

PMID- 16785600
TI  - Gender differences in neurological disease: role of estrogens and cytokines.
AB  - Increasing evidence suggests that inflammatory response may be a critical
      component of different brain pathologies. However, the role played by this
      reaction is not fully understood. The present findings suggest that
      neuroinflammtory mediators such as cytokines may be involved in a number of key
      steps in the pathological cascade of events leading to neuronal injury. This
      hypothesis is strongly supported by experimental and clinical observations
      indicating that inhibition of the inflammatory reaction correlates with less
      neuronal damage. Estrogens are thought to play a role in the sex difference
      observed in many neurological diseases with inflammatory components including
      stroke, Alzheimer's and Parkinson's diseases, multiple sclerosis, or amyotrophic
      lateral sclerosis. Clinical and experimental studies have established estrogen as
      a neuroprotective hormone in these diseases. However, the exact mechanisms
      involved in the neuroprotective effects of estrogens are still unclear. It is
      possible that the beneficial effects of these hormones may be dependent on their
      inhibitory activity on the inflammatory reaction associated with the above
      mentioned brain pathologies. Here, we review the current clinical and
      experimental evidence with respect to the inflammation-modulating effects of
      estrogens as one potential explanatory factor for sexual dimorzphism in the
      prevalence of numerous neurological diseases.

PMID- 16785605
TI  - Effects of long-term adrenalectomy on apoptosis and neuroprotection in the rat
      hippocampus.
AB  - Reduction in corticosterone by acute adrenalectomy (5 d) promotes apoptosis in
      dentate gyrus (DG) granular neurons, an effect concomitant with variations in the
      expression of the Bcl-2 gene family implicated in apoptotic regulation. However,
      no studies exist correlating the effect of long-term adrenalectomy (30 d) on the
      hippocampus in terms of extent of apoptosis and the levels of proteins related to
      an apoptotic cascade. After 5 d of adrenalectomy, we found an increase in
      apoptosis of the DG granular region, correlated with an increase in the
      processing of caspase-9. The magnitude of apoptosis 30 d after adrenalectomy was
      reduced in the DG granular layer compared with 5 d after adrenalectomy, in close
      relation to a reduction in the level of processed caspase-9. To understand how
      the increase in cell survival long after adrenalectomy occurs, we analyzed
      changes in the expression of genes and proteins related to apoptosis. Long-term
      adrenalectomy did not change hippocampal pro-apoptotic Bax or antiapoptotic Bcl-2
      mRNA levels or protein content with respect to control. However, we found an
      increase in mRNA levels of the GD's Bcl-x gene, in parallel with the increase in
      anti-apoptotic BCL-XL protein levels. These results suggest the reduction in
      apoptosis observed after long-term adrenalectomy occurs through mechanisms that
      repress proapoptotic genes previously found to be increased at shorter times of
      adrenalectomy.

PMID- 16785604
TI  - Immune modulation by estrogens: role in CNS HIV-1 infection.
AB  - Experimental and epidemiological data suggest that estrogen can be protective in
      both brain injury and infection. While estrogens can act directly on neurons to
      promote neuronal survival, estrogen also has antiinflammatory properties that may
      contribute to overall neuroprotection. Accordingly, estrogens may have particular
      relevance in chronic neuroimmune disorders such as HIV dementia. As AIDS is now a
      leading cause of death among women in their reproductive years, understanding the
      role that female sex hormones might play in the physiology of HIV-1 infection is
      especially critical. Indeed, there is accumulating evidence that many
      manifestations of HIV differ in women. For instance, it is now well established
      that women present with a lower viral titer at the time of seroconversion, have
      lower HIV viral loads compared to men at similar stages of disease, and may have
      altered disease progression during pregnancy. Conversely, while epidemiological
      studies suggest that women may be more vulnerable to certain late-stage AIDS
      related illnesses including HIV dementia, there is accumulating data that
      strongly suggest an estrogen-deficient state is associated with long-term HIV
      infection in some women. Evaluated as a whole, existing evidence indicates that
      estrogen can directly protect neurons from damage, can modulate brain
      inflammation, and could act to maintain low titers of the HIV-1 virus.
      Accordingly, it can be hypothesized that maintenance of serum estradiol levels
      could decrease the incidence of HIV dementia and other AIDS-related neurological
      syndromes in HIV-1 positive women. In this article, we both summarize current
      understanding and present new data related to the potential mechanisms whereby
      estrogen could modulate the mechanics and the consequences of HIV-1 infection in
      the brain and thereby thwart the development of HIV dementia.

PMID- 16785606
TI  - Effects of mitiglinide on glucose-induced insulin release into the portal vein
      and fat-induced triglyceride elevation in prediabetic and diabetic OLETF rats.
AB  - OBJECTIVE: The effect of single-dose mitiglinide on glucose and lipid metabolism
      was examined in OLETF rats with spontaneous type 2 diabetes in which the early
      insulin response following glucose challenge is known to diminish over time and
      become lost with aging. METHODS: (1) With catheters inserted into the portal
      veins, 12-wk-old prediabetic OLETF rats were given an OGTT of 1 g/kg after 17 h
      of fasting. Eight rats each were orally given mitiglinide 1 mg/kg, nateglinide 50
      mg/kg, or glibenclamide 1 mg/kg, vs 0.5% carboxymethylcellulose (CMC) as control,
      and were given an OGTT immediately afterward. Following oral administration of
      mitiglinide, nateglinide, glibenclamide, or 0.5% CMC, the 24-wk-old overt
      diabetic OLETF rats were immediately given an OGTT of 1g/kg. (2) After 17 h of
      fasting, 24-wk-old OLETF rats were subjected to a fat-loading test. Eight rats
      each were given mitiglinide 3 mg/kg, glibenclamide 1 mg/kg, or glimepiride 1
      mg/kg, vs 0.5% CMC, and were given soy oil 2 g/kg immediately afterward. They
      were also given mitiglinide orally and examined for LPL mRNA expression in their
      adipose tissue. RESULTS: (1) After OGTT, mitiglinide produced a significant
      increase in portal insulin levels 15 min after its administration, as well as a
      significant decrease in peripheral glucose levels 15-120 min after its
      administration in the OLETF rats. Likewise, nateglinide produced an increase in
      portal insulin levels and a decrease in peripheral glucose levels shortly after
      its administration in these rats. Glibenclamide increased portal insulin levels
      for an extended time after its administration, and significantly decreased
      peripheral glucose levels in the rats 120-300 min after its administration in the
      rats. In contrast, as in the 12-wk-old rats, a precipitous rise in insulin
      secretion was seen in the portal vein of 24-wk-old rats given mitiglinide, which
      peaked 15 min after mitiglinide administration, but the insulin levels continued
      to increase for 120 min or longer in the 24-wk-old rats given glibenclamide. In
      addition, as in the 12-wk-old rats, a significant decrease in glucose levels in
      peripheral blood was noted 30 and 60 min after mitiglinide administration and 300
      min after glibenclamide administration in the 24-wk-old rats. (2) Mitiglinide
      increased LPL mRNA expression 120 min after its administration, and significantly
      decreased peripheral TG and chylomicron- TG levels after fat challenge in the 24
      wk-old OLETF rats. CONCLUSION: Mitiglinide exhibited fast-onset and short-acting
      insulin-secretagogic effects, inhibiting post-glucose challenge increases in
      glucose levels and post-fat challenge increases in TG levels.

PMID- 16785603
TI  - Effects of age, gender, and gonadectomy on neurochemistry and behavior in animal
      models of Parkinson's disease.
AB  - The effects of aging and gender on the neurochemistry of the dopaminergic system
      have been studied extensively; however, data on comparative behavioral
      consequences of lesions of the dopaminergic system in aging and in female animals
      are limited. This study presents experimental results on the behavioral and
      morphological outcome in young, aging, and gonadectomized male and female rats in
      the 6-OHDA model of Parkinson's disease. Both young and aging male animals were
      more susceptible to 6-OHDA than females: female rats had significantly less
      dopaminergic cell loss and showed a higher degree of behavioral recovery.
      Although the dopaminergic cell loss was only slightly more in the aging rats of
      the same sex, they showed more severe behavioral deficits in both gender groups.
      Ovariectomy did not significantly influence the dopaminergic cell loss, but
      behavioral recovery was worse when compared to non-ovariectomized females. In
      contrast, castrated males had significantly less dopaminergic cell loss than non
      castrated males, but the behavioral recovery was not significantly better. The
      obtained results are discussed in light of the available literature on the age
      and gender differences in animals models of Parkinson's disease.

PMID- 16785608
TI  - Adenine nucleotide pattern in rat pancreatic islets exposed to nutrient
      secretagogues.
AB  - The effects of D-glucose, D-mannose, D-galactose, Dglyceraldehyde, pyruvate, L
      lactate, 2-ketoisocaproate, L-leucine, and/or L-glutamine on the ATP and ADP
      content of rat isolated pancreatic islets were reevaluated in order to compare
      changes evoked by these nutrient secretagogues in the islet ATP content and
      ATP/ADP ratio to their effects upon insulin release. Although being compatible
      with the fuel concept for nutrient-stimulated insulin secretion, the results of
      this study also argue against the monolithic view that the adenine nucleotide
      pattern in islet cells represents the sole coupling factor between metabolic and
      more distal events in the process of nutrient-stimulated insulin release.

PMID- 16785607
TI  - Fibroblast growth factor-2 and epidermal growth factor modulate prolactin
      responses to TRH and dopamine in primary cultures.
AB  - Fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are
      expressed in most tissues of the organism including pituitary. FGF-2 increases
      PRL levels and PRL mRNA in GH3 cells and primary cultures, and it has been
      involved in the lactotroph proliferation and hyperplasia. EGF also increases PRL
      levels in vitro. However, the effects of these two factors in the responses of
      lactotroph cells to TRH and dopamine (DA) remain to be clarified. In the present
      work we have studied the modulator activity of FGF-2 and EGF on in vitro PRL in
      responses to TRH and DA in primary cultures from in vivo vehicle- or estrogen
      (E2)-treated rats. We have found that FGF-2 (2 x 10(-11) M) prevents the EGF
      induced dose-dependent increase in PRL levels in control cells, and reversed the
      EGF-stimulating effects in cells from E2-treated rats. Both FGF-2 (2 x 10(-11) M)
      and EGF (6.6 x 10(-9) M) significantly increase (>30% and >120%, respectively)
      the PRL levels in response to TRH (10(-6), 10(-5) M). FGF-2 blocked the
      inhibitory effects of low doses of DA (10(-9) M). EGF was unable to do so,
      although markedly increased (>200%) the post-DA PRL rebound. In cells from in
      vivo E2-treated rats, FGF-2 increased (>50%) the PRL secretion in response to
      TRH, while EGF reduced responses to high doses of TRH (10(-6), 10(-5) M). In
      addition, FGF-2 reversed and EGF increased the inhibitory effects of DA. Both FGF
      2 and EGF completely blocked the post-DA PRL rebound, in these cells. Taken
      together our data suggest that FGF-2 and EGF are important regulators of
      lactotroph responsiveness to TRH and DA in vitro, although their actions are
      highly dependent on estrogenic milieu.

PMID- 16785609
TI  - Tritiated taurine handling by isolated rat pancreatic islets.
AB  - A gating of volume-sensitive anion channels may participate in the depolarization
      of the plasma membrane caused by high concentrations of D-glucose in insulin
      producing B-cells of the endocrine pancreas. The efflux of tritiated taurine from
      prelabeled cells is currently used to assess changes in the activity of such
      channels. The handling of [1,2-3H]taurine by isolated rat pancreatic islets was
      therefore investigated. The net uptake of [1,2-3H]taurine was found to represent
      a concentration-, time-, and temperature-dependent process. It was progressively
      increased in the range of D-glucose concentrations between 2.8 and 8.3 mM, but no
      further increase was observed at 16.7 mM D-glucose. Over 15 min incubation, the
      efflux of radioactivity from prelabeled islets was inhibited by MK571 (1.0 mM).
      It was increased in response to hypoosmolarity both in the presence and absence
      of extracellular Na+. Whether in salt-balanced or Na+-deprived media, the efflux
      of radioactivity from prelabeled islets increased in response to a rise in D
      glucose concentration from 2.8 to 5.6 or 8.3 mM, but decreased when the
      concentration of the hexose was further increased from 8.3 to 16.7 mM. In
      perifused islets, however, the radioactive efflux from prelabeled islets was
      inhibited, in a concentration- related manner, when islets first deprived of D
      glucose for 45 min were then exposed to 2.8, 5.6, or 16.7 mM D-glucose. Likewise,
      in prelabeled and perifused islets first exposed for 45 min to 4.0 mM D-glucose,
      a later rise in hexose concentration to 8.3 mM failed to affect significantly
      effluent radioactivity, while an increase in hexose concentration from 4.0 to
      16.7 mM inhibited the radioactive outflow. In these perifusion experiments, the
      rise in D-glucose concentration provoked the expected changes in insulin output.
      The findings obtained in islets examined immediately after preincubation in the
      presence of [1,2-3H]taurine are consistent with the presence of volume-sensitive
      anion channels in islet cells and with a gating of such channels in response to a
      rise in D-glucose concentration from 2.8 to 5.6-8.3 mM. However, the radioactive
      fractional outflow rate from prelabeled islets seems to reach its highest value
      at about 8.3 mM D-glucose, being unexpectedly decreased at a higher concentration
      (16.7 mM) of the hexose. In conclusion, the pleiotropic effects of D-glucose upon
      tritiated taurine outflow from prelabeled rat islets, which could conceivably be
      ascribed to differences in the handling of this amino sulfonic acid by distinct
      islet cell types, indicates that the present approach is far from optimal to
      characterize unambiguously the regulation by the hexose of volume-sensitive anion
      channel activity in insulin-producing islet cells.

PMID- 16785610
TI  - Adiponectin and resistin in the neonatal rat: effects of dexamethasone and
      hypoxia.
AB  - Hypoxia is a common neonatal stress that induces insulin resistance and a
      decrease in body weight gain. Dexamethasone is often used to treat neonatal
      cardiopulmonary disease, and also leads to insulin resistance and a decrease in
      body weight gain. The current study addressed the hypothesis that serum
      concentrations of the adipokines adiponectin and/or resistin are altered during
      hypoxia and/or dexamethasone therapy in neonatal rats. Rat pups with their
      lactating dams were exposed to hypoxia (11% O2) from birth and treated with a
      tapering regimen of dexamethasone from postnatal day (PD) 3-6. Serum adiponectin
      and resistin were measured on PD7. Hypoxia and dexamethasone independently
      decreased body weight gain and increased adiponectin levels. The combination of
      hypoxia and dexamethasone did not further increase adiponectin. Dexamethasone
      caused a small increase in resistin in normoxic pups, which may facilitate the
      hyperinsulemic- normoglycemic state we previously described. We also conclude
      that adiponectin is increased during hypoxia in response to a decrease in the
      sensitivity to insulin.

PMID- 16785611
TI  - Changes in serum inhibin levels and immunolocalization of inhibin/activin
      subunits during the breeding season in the wild male Japanese black bear (Ursus
      thibetanus japonicus).
AB  - The objective of this study was to investigate the changes in secretion of
      inhibin and cellular localization of inhibin alpha and inhibin/activin (beta(A)
      and beta(B)) subunits during the breeding season in the wild male Japanese black
      bear. Histological observations of testes were performed and seminiferous tubule
      diameters were measured. The sections of the testes were immunostained by the
      avidin- biotin-peroxidase complex method (ABC) using polyclonal antisera raised
      against porcine inhibin alpha, inhibin/ activin beta(A), and inhibin/activin
      beta(B) during the breeding season. Serum concentrations of immunoreactive (ir
      )inhibin, testosterone, and luteinizing hormone (LH) were measured by
      radioimmunoassay. Higher values of seminiferous tubule diameters and all types of
      spermatogenic cells including mature-phase spermatozoa were found during the
      breeding season. There were seasonal changes in serum concentrations of ir
      inhibin, testosterone, and LH. Ir-inhibin was positively correlated with
      testosterone, and LH. In addition, immunoreactivity of inhibin alpha, beta(A),
      and beta(B) subunits were also detected in Sertoli and Leydig cells during the
      breeding season. These results suggest that Japanese black bear testes may
      secrete bioactive inhibins during the breeding season and that the circulating
      inhibin may be a useful indicator of the testicular function in wild male
      Japanese black bears.

PMID- 16785612
TI  - Japanese IGT subjects with high insulin response are far more frequently
      associated with the metabolic syndrome than those with low insulin response.
AB  - Impaired glucose tolerance (IGT) represents a prediabetic state positioned
      somewhere between normal glucose tolerance and diabetes, which is also assumed to
      make individuals in this state highly susceptible to atherosclerotic disease. IGT
      also accounts for a highly heterogeneous population, with the condition varying
      from individual to individual. In this study, we stratified subjects with IGT by
      their insulin response and compare the pathology of IGT when it is associated
      with high or low insulin response to gain insight into the diverse pathology of
      IGT. Of the male corporate employees who underwent 75 g OGTT at the corporation's
      healthcare center, 150 individuals diagnosed with IGT (isolated IGT, combined IGT
      and IFG) comprised our study subjects. The study subjects were stratified into
      four quartiles by percentile AUC for insulin, and those in the 25th or less
      percentile were defined as the low insulin response group (n = 37), vs those in
      the 76th or greater percentile defined as the high insulin response group (n =
      38), and these groups were compared. There was no significant difference observed
      between the two groups in regard to post-OGTT glucose response and area under the
      glucose curve. However, the high insulin response group was associated with
      higher BMI, subcutanesous fat area, uric acid levels, HOMA-beta cell values, and
      delta insulin/delta glucose (30 min) than the low insulin response group. The
      number of risk factors for the metabolic syndrome detected (as defined by the
      ATPIII diagnostic criteria) per subject was 2.84 +/- 0.17 and 2.08 +/- 0.20,
      respectively, in the high insulin response group and in the low insulin response
      group, with the number significantly (p < 0.05) higher in the high insulin
      response group. Furthermore, the incidence of the metabolic syndrome as defined
      by the ATPIII diagnostic criteria was 63.2% (24/38) in the high insulin response
      group vs 32.4% (12/27) in the low insulin response group, with the incidence
      significantly (p < 0.01) higher in the high insulin response group. Likewise, the
      incidence of the metabolic syndrome as defined by the Japanese diagnostic
      criteria was found to be significantly (p < 0.05) higher in the high insulin
      response group at 50% (19/38) compared to 27.0% (10/37) in the low insulin
      response group. Our study findings suggest that IGT subjects with high insulin
      response and those with low insulin response vary greatly in regard to the number
      of atherosclerotic risk factors complicated and the frequency with which they are
      associated with the metabolic syndrome. It is also shown in middle-aged Japanese
      males that of the two forms of IGT, IGT with high insulin response is more
      closely linked to the pathogenesis of atherosclerotic cardiovascular disease.

PMID- 16785613
TI  - Role of hypoadiponectinemia in the metabolic syndrome and its association with
      post-glucose challenge hyper-free fatty acidemia: a study in prediabetic Japanese
      males.
AB  - We investigated the role of hypoadiponectinemia in the metabolic syndrome (MS),
      as well as its association with post-glucose challenge hyper-free fatty acidemia
      in the clinical setting. The study subjects comprised 177 corporate employees
      shown to have a fasting plasma glucose (FPG) level of 125 mg/dL or less in a 75 g
      OGTT in the corporation's healthcare center. When divided into those who met the
      Japanese criteria for the metabolic syndrome (MS group; n = 45) and those who did
      not (Non-MS group; n = 132), the MS group was shown to have significantly lower
      adiponectin levels than the Non-MS group, and tended to show higher high
      sensitivity C-reactive protein (CRP) values than the Non-MS group, while not
      achieving statistical significance. The MS group showed higher baseline glucose
      levels; higher baseline, 30-, 60-, and 120-min post-challenge insulin levels;
      higher 30-, 60-, and 120-min post-challenge free fatty acid levels than the Non
      MS group. Additionally, there was a significant, negative correlation between
      adiponectin levels, area under the free fatty acid curve, and area under the
      insulin curve at OGTT (r = -0.24, p < 0.01; r = -0.21, p < 0.01, respectively).
      When the patients were divided by adiponectin level into four groups to examine
      the number of risk factors for MS detected per patient and the incidence of MS,
      the lower the adiponectin level, the more risk factors were found per patient,
      with 68% of patients with an adiponectin level of less than 4 microg/mL found to
      have MS. In those with an adiponectin level of less than 4 microg/mL, BMI values,
      uric acid levels, HOMA-R values, and the number of risk factors for MS involved
      per patient were shown to be higher than in those with an adiponectin level of 4
      microg/mL or greater. Furthermore, the following risk factors for MS were more
      frequently found in those with an adiponectin level of less than 4 microg/mL than
      in those with an adiponectin level of 4 microg/mL or greater: VFA > or = 100 cm2
      (OR 12.8, p < 0.001); TG > or = 150 mg/dL (OR 3.2, p < 0.05); HDLC < 40 mg/dL (OR
      1.9, p = 0.29); BP > or = 130/85 mmHg (OR 2.2, p = 0.15); and FPG > or = 110
      mg/dL (OR 1.9, p = 0.29). Again, the incidence of MS (OR 7.6, p < 0.001) by the
      ATPIII criteria, as well as that by the Japanese criteria (OR 8.6, p < 0.001),
      was found to be higher in those with an adiponectin level of less than 4
      microg/mL than in those with an adiponectin level of 4 microg/mL or greater. Our
      study results suggest that adiponectin is closely associated with the multiple
      risk factors that go to make up the MS, suggesting a role for hypoadiponectinemia
      as a surrogate marker for the MS and further appear to suggest that post
      challenge hyper-free fatty acidemia may account in part for hypoadiponectinemia
      in the MS.

PMID- 16785614
TI  - Makorin RING finger protein 1 (MKRN1) has negative and positive effects on RNA
      polymerase II-dependent transcription.
AB  - Through its transcriptional activities, the proto-oncoprotein c-Jun can regulate
      cellular proliferation, survival, and differentiation. We have established a
      novel yeast assay that screens for repressors of c-Jun transcriptional activity.
      This screen led to the identification of a ubiquitously expressed novel RING zinc
      finger protein, termed Makorin RING zinc finger protein 1 (MKRN1), recently shown
      to act as an E3 ubiquitin ligase. Overexpression of MKRN1 in mammalian cells
      inhibited the transcriptional activities of not only c-Jun, but also the nuclear
      receptors, the androgen receptor, and the retinoic acid receptors. Truncation
      analysis indicates that both the amino and carboxy termini are required for this
      transrepression activity. Surprisingly, when fused to the heterologous DNAbinding
      domain of GAL4, MKRN1 activates, rather than inhibits, a GAL4-responsive reporter
      plasmid. In addition, truncation of either the amino- or carboxy-terminal half of
      MKRN1 disrupts its transactivation activity, the same observation that was made
      on its transrepression activity. These results demonstrate that MKRN1 has
      transcriptional activity and suggest that its transrepression and transactivation
      functions are mediated by the same mechanism. Interestingly, disruption of
      MKRN1's ubiquitin ligase activity does not affect its inhibitory transcriptional
      activity. Thus, MKRN1 may represent a nuclear protein with multiple nuclear
      functions, including regulating RNA polymerase II-catalyzed transcription.

PMID- 16785615
TI  - Chronic treatment with either dexfenfluramine or sibutramine in diet-switched
      diet-induced obese mice.
AB  - Dexfenfluramine (DEX) and sibutramine (SIB) are effective antiobesity agents.
      Their effects on weight control and hormone profile have not been previously
      studied in diet-switched diet-induced obese (DIO) mice, in which treatment is
      initiated upon cessation of a low-fat diet and resumption of a high-fat diet.
      Furthermore, their effects on circulating ghrelin in obese humans or in animal
      models of obesity have not yet been reported. Male C57Bl/6J DIO mice after 16 wk
      on a high-fat diet (HF, 60 kcal% fat) were switched to a low-fat diet (LF, 10
      kcal% fat) for 50 d. HF diet resumed concurrently with treatment for 28 d with
      DEX 3 and 10 mg/kg, twice a day (BID); SIB 5 mg/kg BID; or vehicle. Rapid weight
      regain ensued in vehicle-treated DIO mice. DEX or SIB treatment significantly
      blunted the body weight gain. Caloric intake was decreased acutely by DEX or SIB
      vs vehicle during the first 2 d treatment, but returned to control after 5 d. At
      the end of study, epididymal fat weight and whole body fat mass determined by
      DEXA scan were decreased by DEX 10 mg/kg, and whole body lean mass decreased with
      DEX 3 mg/kg treatment. Circulating ghrelin on d 28 was increased with either DEX
      3 or 10 mg/kg treatment, while growth hormone and insulin were decreased. Leptin
      was also decreased in the DEX 10 mg/kg group. SIB did not significantly affect
      fat mass, ghrelin, growth hormone, insulin, or leptin. Mice chronically fed LF
      diet maintained a lower caloric intake, gained less weight and fat mass than diet
      switched mice, and had higher ghrelin and lower insulin and leptin. In summary,
      weight regain in diet-switched DIO mice is delayed with either DEX or SIB
      treatment. DEX treatment of diet-switched DIO mice decreased growth hormone,
      insulin, leptin, fat mass, lean mass, and increased ghrelin, while SIB only
      decreased body weight.

PMID- 16785616
TI  - Selection of fluorophore and quencher pairs for fluorescent nucleic acid
      hybridization probes.
AB  - With the introduction of simple and relatively inexpensive methods for labeling
      nucleic acids with nonradioactive labels, doors have been opened that enable
      nucleic acid hybridization probes to be used for research and development, as
      well as for clinical diagnostic applications. The use of fluorescent
      hybridization probes that generate a fluorescence signal only when they bind to
      their target enables real-time monitoring of nucleic acid amplification assays.
      The use of hybridization probes that bind to the amplification products in real
      time markedly improves the ability to obtain quantitative results. Furthermore,
      real-time nucleic acid amplification assays can be carried out in sealed tubes,
      eliminating carryover contamination. Because fluorescent hybridization probes are
      available in a wide range of colors, multiple hybridization probes, each designed
      for the detection of a different nucleic acid sequence and each labeled with a
      differently colored fluorophore, can be added to the same nucleic acid
      amplification reaction, enabling the development of high-throughput multiplex
      assays. It is therefore important to carefully select the labels of hybridization
      probes, based on the type of hybridization probe used in the assay, the number of
      targets to be detected, and the type of apparatus available to perform the assay.
      This chapter outlines different aspects of choosing appropriate labels for the
      different types of fluorescent hybridization probes used with different types of
      spectrofluorometric thermal cyclers.

PMID- 16785617
TI  - Choosing reporter-quencher pairs for efficient quenching through formation of
      intramolecular dimers.
AB  - Fluorescent energy transfer within dual-labeled oligonucleotide probes is widely
      used in assays for genetic analysis. Nucleic acid detection/amplification
      methods, such as real-time polymerase chain reaction, use dual-labeled probes to
      measure the presence and copy number of specific genes or expressed messenger
      RNA. Fluorogenic probes are labeled with both a reporter and a quencher dye.
      Fluorescence from the reporter is only released when the two dyes are physically
      separated via hybridization or nuclease activity. Fluorescence resonance energy
      transfer (FRET) is the physical mechanism that is most often cited to describe
      how quenching occurs. We have found that many dual-labeled probes have enhanced
      quenching through a nonFRET mechanism called static quenching. Static quenching,
      which is also referred to as contact quenching, can occur even in "linear"
      oligonucleotide probes that have no defined secondary structure to bring the
      reporter and quencher pair into proximity. When static quenching accompanies FRET
      quenching, the background fluorescence of probes is suppressed. This chapter
      describes how to pair reporter and quencher dyes for dual-labeled probes to
      maximize both FRET and static quenching. Data comparing various reporter-quencher
      pairs is presented as well as protocols for evaluation and optimization of the
      probes.

PMID- 16785618
TI  - Detection of DNA hybridization using induced fluorescence resonance energy
      transfer.
AB  - Induced fluorescence resonance energy transfer (iFRET) is a variation of
      resonance energy transfer that is particularly well-suited for the detection of
      DNA hybridization. The underlying mechanism involves monitoring changes in
      fluorescence that are the result of an energy transfer reaction between a
      specific pair of donor and acceptor moieties. In iFRET, the donor is a dye that
      only fluoresces while interacting with double-stranded DNA and the acceptor is
      dye that is covalently linked to an oligonucleotide probe. Hybridization of the
      probe to its complement induces excitement of the donor dye and subsequent energy
      transfer to the acceptor dye. The energy transfer reaction (and concomitant
      hybridization status) can easily be followed by monitoring the fluorescence
      output of the acceptor dye. Because the interaction of the donor dye is
      reversible and dependent on the presence of double-stranded DNA, iFRET is
      extremely useful and herein demonstrated in the generation of DNA melting curves.

PMID- 16785619
TI  - Detecting RNA/DNA hybridization using double-labeled donor probes with enhanced
      fluorescence resonance energy transfer signals.
AB  - Fluorescence resonance energy transfer (FRET) occurs when two fluorophores are in
      close proximity, and the emission energy of a donor fluorophore is transferred to
      excite an acceptor fluorophore. Using such fluorescently labeled oligonucleotides
      as FRET probes, makes possible specific detection of RNA molecules even if
      similar sequences are present in the environment. A higher ratio of signal to
      background fluorescence is required for more sensitive probe detection. We found
      that double-labeled donor probes labeled with BODIPY dye resulted in a remarkable
      increase in fluorescence intensity compared to single-labeled donor probes used
      in conventional FRET. Application of this double-labeled donor system can improve
      a variety of FRET techniques.

PMID- 16785620
TI  - Oscillating probe for dual detection of 5'PO4 and 5'OH DNA breaks in tissue
      sections.
AB  - Several types of DNA cuts are used as markers of apoptosis for detection of
      apoptotic cells in situ. We recently introduced a ligase-based in situ assay that
      is specific for a single type of DNA damage--a double-strand break of DNase I
      type, bearing 5'PO4. Here we describe a vaccinia topoisomerase I-based approach
      to label another type of DNA damage in situ--a double-strand break of DNase II
      type, bearing 5'OH. The assay uses a new type of probe, a molecular oscillator.
      The probe self-assembles in solution out of a dual-hairpin oligonucleotide and
      vaccinia topoisomerase I. The enzyme continuously separates and religates two
      fluorescently labeled hairpins, which can participate in energy transfer. We
      describe the successful combination of topoisomerase-and ligase-based systems
      into an in situ assay. The assay uses an oscillating probe for simultaneous
      detection of two types of DNA cuts in tissue sections.

PMID- 16785621
TI  - Using molecular beacons for sensitive fluorescence assays of the enzymatic
      cleavage of nucleic acids.
AB  - A novel method for DNA enzymatic cleavage assays using molecular beacons (MBs) as
      the substrate for nuclease is described. An MB is a hairpin-shaped DNA probe that
      is labeled with a fluorescent dye at one end and a quencher at the other end. The
      loop sequence of the MB can be used as the substrate for single-stranded specific
      nucleases, whereas the stem of the MB can be designed as the substrate for
      restriction enzymes. The enzymatic cleavage breaks the MB into fragments and
      leads to the distance separation of the quencher and the fluorophore, resulting
      in an increase in the fluorescent signal. Up to an 80-fold signal-to-noise ratio
      was observed when these probes were cleaved by nucleases. Taking advantage of the
      MB's detection-without-separation property, this method allows for the real-time
      detection of DNA cleavage, which is useful for the characterization of DNA
      nuclease activity as well as the study of steady-state cleavage reaction
      kinetics. With its simplicity, convenience, high sensitivity, and excellent
      reproducibility, this method has the potential to be used in the study of both
      natural and artificial nucleic acid-cleaving enzymes.

PMID- 16785622
TI  - A continuous assay for DNA cleavage using molecular break lights.
AB  - Exploring the properties of molecules that cleave DNA (i.e., enzymatic nucleases,
      chemical footprinting agents, and naturally occurring DNA cleaving antibiotics)
      has been an ongoing process with benefits extending toward both laboratory and
      clinical applications. Despite the progress that has been made toward
      understanding the mechanics of DNA cleavage, a simple and continuous assay for
      detecting DNA cleavage has been lacking. Herein, we describe the molecular break
      light assay, wherein a single oligo-nucleotide modified by a 5'-fluorophore-3'
      quencher pair adopting a stem-loop structure with an appropriate DNA recognition
      site, provides for the rapid assaying of DNA cleavage with high sensitivity.
      Furthermore, the described methodology is highly convenient in that it is readily
      adaptable to common laboratory fluorometers and multi-well plate/ array systems,
      which may provide the basis for high-throughput screening of novel DNA cleaving
      agents. This assay may also be further extended to natural or "unnatural"
      transcription factor protection assay systems.

PMID- 16785623
TI  - Homogeneous detection of nucleic acids using self-quenched polymerase chain
      reaction primers labeled with a single fluorophore (LUX primers).
AB  - Multiplex quantitative polymerase chain reaction (PCR) based on novel design of
      fluorescent primers is described. Self-quenched fluorogenic primers are labeled
      with a single fluorophore on a base close to the 3'-end with no quencher
      required. A tail of 5-7 nucleotides is added to the 5'-end of the primer to form
      a blunt-end hairpin when the primer is not incorporated into a PCR product. This
      design provides a low initial fluorescence of the primers that increases upon
      formation of the PCR product. The hairpin oligonucleotides (DeltaG from -1.6 to 
      5.8 kcal/mol) are as efficient as linear primers and provide additional
      specificity to the PCR by preventing primer-dimers and mispriming. Self-quenched
      primers could be designed manually or by specialized software and could be used
      for real-time gene quantitation. Targets of 10-107 copies could be detected with
      precision in PCR using fluorescein-labeled primers for variable genes and JOE
      labeled primers for the reference genes. This method could also be used to detect
      single nucleotide polymorphism by allele-specific PCR. In conclusion, self
      quenched primers are an efficient and cost-effective alternative to fluorescence
      resonance energy transfer-labeled oligonucleotides.

PMID- 16785624
TI  - Use of self-quenched, fluorogenic LUX primers for gene expression profiling.
AB  - Application of a real-time detection system based on a novel primer design in
      gene expression profiling is described. In this system, called LUX (Light Upon
      eXtension), the generation of signal is based on a single fluorescent dye
      molecule that is attached to an oligonucleotide close to the 3'-end. A primer
      design software is available that identifies LUX primer pairs based on a set of
      rules for optimum signal development. The use of LUX fluorogenic primers to
      determine the expression patterns of various transcripts during differentiation
      in the P-19 mouse neuronal model is described.

PMID- 16785625
TI  - TaqMan reverse transcriptase-polymerase chain reaction coupled with capillary
      electrophoresis for quantification and identification of bcr-abl transcript type.
AB  - Real-time TaqMan polymerase chain reaction (PCR) assays allow quantification of
      the initial amount of target in a specimen, specifically, and reproducibly. The
      major limitation of TaqMan PCR assays is that they do not detect the size of the
      amplified target sequence. TaqMan PCR coupled with capillary electrophoresis is
      an alternative approach that can be used to circumvent this limitation. In this
      chapter, the utility of this approach in the identification and quantification of
      bcr-abl fusion transcripts produced as a result of t(9;22)(q34;q11) in chronic
      myelogenous leukemia is described. In this assay, abl primer labeled at its 5'
      end with the fluorescent dye NED (Applied Biosystems [ABI], Foster City, CA) is
      incorporated into the bcr-abl fusion product during the real-time PCR. The
      incorporated NED fluorescent dye is then used subsequently to identify the
      specific fusion transcript present in a given specimen by high-resolution
      capillary electrophoresis and GeneScan (ABI) analysis. Knowledge of the type of
      fusion transcript present in a specimen is useful to rule out false-positive
      results and to compare clones before and after therapy.

PMID- 16785626
TI  - Quantitative TaqMan assay for the detection and monitoring of cytomegalovirus
      infection in organ transplant patients.
AB  - Quantitative polymerase chain reaction assays have become the most common methods
      in the determination of viral load during cytomegalovirus (CMV) infection of
      transplant patients. In recent years, the development of automated nucleic acid
      extraction devices together with the introduction of real-time technology have
      been important elements for improvements of these assays. This chapter describes
      a method for the quantitation of CMV DNA viral load in the plasma samples of
      organ transplant patients. The method is based on MagNA Pure LC nucleic acid
      extraction system (Roche) and the TaqMan real-time technology. MagNA Pure LC is
      highly automated procedure with which 32 plasma samples could be processed within
      1.5 h. TaqMan chemistry and Sequence Detector System 7900HT device (Applied
      Biosystems) are used for the quantitative amplification of the CMV genome. The
      chapter also describes preparation of the plasmid, which is needed to achieve a
      quantitative standard curve for quantitation.

PMID- 16785627
TI  - Real-time detection and quantification of telomerase activity utilizing energy
      transfer primers.
AB  - A novel closed-tube format telomeric repeat amplification protocol specifically
      adapted to real-time detection and quantification of telomerase activity was
      developed. The assay utilizes energy transfer primers, which emit fluorescence
      only upon incorporation into polymerase chain reaction (PCR) amplification
      products. The assay, performed on a real-time detection instrument, is highly
      reproducible, sensitive, and specific. Telomerase activity in as few as 10
      cultured cells can be quantified with a linear dynamic range more than 2.5 logs.
      In addition, the presence of potential PCR inhibitor(s) is readily detectable by
      inclusion of an internal PCR control labeled with a second color fluorescence.

PMID- 16785628
TI  - Invader assay for single-nucleotide polymorphism genotyping and gene copy number
      evaluation.
AB  - The Invader assay (Third Wave Technologies) is a homogeneous, isothermal DNA
      probe-based method for sensitive detection of nucleic acid sequences. Invader
      reactions are performed directly on genomic DNA or total RNA targets; however,
      polymerase chain reaction- or reverse transcriptase polymerase chain re action
      amplified products can also be used. Detection is achieved through target
      specific signal amplification instead of target amplification. The assay is a
      highly accurate and specific detection method for both qualitative and
      quantitative analysis of single-nucleotide changes, insertions or deletions, gene
      copy number, infectious agents, and gene expression.

PMID- 16785629
TI  - Real-time quantitative polymerase chain reaction analysis of mitochondrial DNA
      point mutation.
AB  - Mitochondrial respiratory chain disorders are a group of clinically and
      genetically heterogeneous diseases. Several mitochondrial (mt)DNA point mutations
      are responsible for common mitochondrial diseases. These pathogenic mtDNA point
      mutations are usually heteroplasmic. Molecular diagnosis of the disease requires
      both qualitative detection of the mutation and quantitative analysis of the
      mutant heteroplasmy. In this report, two methods based on real-time quantitative
      polymerase chain reaction (PCR) analysis are used. The first method utilizes wild
      type or mutant sequence-specific TaqMan probe, which is labeled with a
      fluorescent reporter molecule at the 5'-end of the oligonucleotide probe and a
      quencher at the 3'-end of the probe. The second method utilizes sequence-specific
      primers to amplify the wild-type or mutant sequence followed by SYBR green
      detection of PCR products. Both methods allow simultaneous detection and
      quantification of the mutant mtDNA. In this chapter, we describe the detailed
      procedures regarding the application of fluorescent probes, and real time
      quantitative PCR in the molecular diagnosis of mitochondrial DNA disorders.

PMID- 16785631
TI  - High-throughput genotyping with energy transfer-labeled primers.
AB  - The Amplifluor method for single-nucleotide polymorphisms (SNP) genotyping
      provides homogeneous assays that utilize a pair of universal energy transfer
      labeled primers. The main advantage of this single-step, loci-independent, low
      cost method is that it can be readily adapted for new SNPs. The development of
      any new SNP assay requires only the design and synthesis of three conventional
      oligonucleotides. Furthermore, Amplifluor-based SNP assays require
      instrumentation found in most laboratories including a thermocycler and
      fluorescent plate-reader. Here, we provide detailed protocols for primer design,
      both manually and using AssayArchitect software. Protocols for SNP analysis are
      provided along with more than 100 examples for common polymorphisms. Specific
      cases including polymorphisms caused by the insertion/deletion of nucleotides,
      and dealing with the AT- and GC-rich sequences are addressed and discussed in
      detail.

PMID- 16785630
TI  - Multiplex single-nucleotide polymorphism detection by combinatorial fluorescence
      energy transfer tags and molecular affinity.
AB  - Combinatorial fluorescence energy transfer (CFET) tags, constructed by exploiting
      fluorescence energy transfer and combinatorial synthesis to generate a large
      number of unique fluorescence emission signatures from a limited number of
      fluorophores, allow multiple biological targets to be identified simultaneously.
      All of the CFET tags can be excited by a single wavelength of 488 nm and analyzed
      by a simple optical system. In genetic analysis, the CFET tags are coupled with
      solid phase capture for multiplex single-nucleotide polymorphism (SNP) detection.
      The design, synthesis, purification of CFET tags, and the methods to use the CFET
      tags and molecular affinity for SNP detection in the retinoblastoma tumor
      suppressor gene are described.

PMID- 16785632
TI  - Distance determination in protein-DNA complexes using fluorescence resonance
      energy transfer.
AB  - Fluorescence resonance energy transfer (FRET) provides distance information
      between a donor and an acceptor dye in the range of 10-100 A. Knowledge of the
      exact positions of some dyes (e.g., fluorescein, rhodamine, or Cy3) with respect
      to nucleic acids and DNA design enables us to translate these data into precise
      structural information using molecular modeling. Here we describe this in vitro
      approach from the design and synthesis of the DNA FRET samples to the
      fluorescence spectroscopy methods and analysis. Advances in the preparation of
      dye-labeled nucleic acid molecules and modern techniques like the measurement of
      FRET in vivo lead to an increased importance of FRET studies in structural and
      molecular biology.

PMID- 16785633
TI  - Multi-fluorophore fluorescence resonance energy transfer for probing nucleic
      acids structure and folding.
AB  - Fluorescence resonance energy transfer (FRET) is a widely used technique to study
      the structure and dynamics of nucleic acids in solution. Such a technique often
      uses only one donor fluorophore and one acceptor fluorophore to probe the
      distance and its changes between the two labeled sites. To fully understand
      molecules with complicated structures, such as three- or four-way DNA junctions,
      several dual-fluorophore experiments have to be performed. Here, we describe an
      emerging alternative technique using multi-fluorophore FRET, in which
      simultaneous labeling of one molecule with several different fluorophores is
      performed to acquire all the distance information in a single experiment. This
      method decreases the number of experiments necessary to perform and increases the
      consistency of the results. In this chapter, FRET study of a tri-fluorophore
      labeled DNAzyme serves as an example to illustrate the design of multi
      fluorophore FRET experiments and the related data processing and analysis. The
      (ratio)A method used to calculate FRET efficiency in dual-fluorophore systems is
      extended to multi-fluorophore systems. An important difference between dual- and
      multi-fluorophore systems is that, when a multi-fluorophore system is used, FRET
      efficiency is no longer a reliable parameter to assess folding. Instead,
      fluorophore-to-fluorophore distance should be used.

PMID- 16785634
TI  - Fluorescent DNAzyme biosensors for metal ions based on catalytic molecular
      beacons.
AB  - In this chapter, methods for designing metal ion sensors using fluorophore- and
      quencher-labeled DNAzymes are discussed. In contrast to the classical molecular
      beacon method based on binding, the methods described here utilize catalytic
      cleavage to release the fluorophore for detection and quantification, making it
      possible to take advantage of catalytic turnovers for signal amplification.
      Unlike classical molecular beacons that detect only nucleic acids, catalytic
      molecular beacons can be applied to different DNAzymes to detect a broad range of
      analytes. The methods described are based on the finding that almost all known
      trans-cleaving DNAzymes share a similar structure comprised of a catalytic
      DNAzyme core flanked by two substrate recognition arms. Using a typical DNAzyme
      called the "8-17" DNAzyme as an example, the design of highly sensitive and
      selective Pb2+ sensors is described in detail. The initial design employs a
      single fluorophore-quencher pair in close proximity, with the fluorophore on the
      5'-end of the substrate and the quencher on the 3'-end of the enzyme. Although
      this sensor is highly sensitive and selective at 4 degrees C, high background
      fluorescence is observed at higher temperatures. Therefore a new design with an
      additional quencher attached to the 3'-end of the substrate is employed to
      suppress background fluorescence. The dual quencher method allows the sensor to
      perform at ambient temperatures with a high signal-to-noise ratio.

PMID- 16785635
TI  - Fluorescent energy transfer readout of an aptazyme-based biosensor.
AB  - Biosensors are devices that amplify signals generated from the specific
      interaction between a receptor and an analyte of interest. RNA structural motifs
      called aptamers have recently been discovered as receptor components for
      biosensors owing to the ease with which they can be evolved in vitro to bind a
      variety of ligands with high specificity and affinity. By coupling an aptamer as
      allosteric control element to a catalytic RNA such as the hammerhead ribozyme,
      ligand binding is transduced into a catalytic event. We have made use of
      fluorescence resonance energy transfer (FRET) to further amplify ligand induced
      catalysis into an easily detectable fluorescence signal. This chapter reviews in
      detail the methods and protocols to prepare a theophylline specific aptazyme and
      to label its substrate with fluorophores. We also include detailed protocols to
      characterize by FRET the binding affinity of the target, theophylline, as well as
      the external substrate to the aptazyme. The chapter should therefore facilitate
      the implementation of RNA-based biosensor components for other analytes of
      interest.

PMID- 16785636
TI  - Fluorescence resonance energy transfer in the studies of guanine quadruplexes.
AB  - A guanine (G)-quadruplex DNA motif has recently emerged as a biologically
      important structure that is believed to interfere with telomere maintenance by
      telomerase. G-quadruplexes exhibit four-stranded structures containing one or
      more nucleic acid strands with central channel able to accommodate metal cations.
      Coordination of certain metal cations stabilizes G-quadruplex as with some
      promising small organic molecules that promote the formation and/or stabilization
      of G-quadruplex. Among many techniques employed to explore properties of G
      quadruplexes, the fluorescence resonance energy transfer (FRET) technique has
      been recognized as a powerful tool to study G-quadruplex formation. This review
      summarizes the current developments in the uses of FRET technique for the
      fundamental structural investigations and its practical applications.
      Applications include FRET-based selection of efficient quadruplex-binding
      ligands, design of a nanomolecular machine, and a molecular aptamer beacon for
      protein recognition. We also describe a technique for detection of potassium ions
      in aqueous solution with the use of quadruplex-based sensor (potassium-sensing
      oligonucleotide).

PMID- 16785637
TI  - Solution-phase molecular-scale computation with deoxyribozyme-based logic gates
      and fluorescent readouts.
AB  - Recent development of solution-phase molecular-scale Boolean calculations using
      deoxyribozymes is potentially an important step toward the development of
      autonomous therapeutic and diagnostic devices. Here, the construction of basic
      YES, AND, ANDNOT, and ANDANDNOT deoxyribozyme-based logic gates is described.
      Protocols for testing gate activity using fluorescent oligonucleotide probes have
      been provided, and pointers for gate optimization are included.

PMID- 16785638
TI  - On-chip protein synthesis for making microarrays.
AB  - Protein microarrays are a miniaturized format for displaying in close spatial
      density hundreds or thousands of purified proteins that provide a powerful
      platform for the high-throughput assay of protein function. The traditional
      method of producing them requires the high-throughput production and printing of
      proteins, a laborious method that raises concerns about the stability of the
      proteins and the shelf life of the arrays. A novel method of producing protein
      microarrays, called nucleic acid programmable protein array (NAPPA), overcomes
      these limitations by synthesizing proteins in situ. NAPPA entails spotting
      plasmid DNA encoding the relevant proteins, which are then simultaneously
      transcribed and translated by a cell-free system. The expressed proteins are
      captured and oriented at the site of expression by a capture reagent that targets
      a fusion protein on either the N- or C-terminus of the protein. Using a mammalian
      extract, NAPPA expresses and captures 1000-fold more protein per feature than
      conventional protein-printing arrays. Moreover, this approach minimizes concerns
      about protein stability and integrity, because proteins are produced just in time
      for assaying. NAPPA has already proven to be a robust tool for protein functional
      assays.

PMID- 16785639
TI  - RCA-enhanced protein detection arrays.
AB  - There are many instances in which it is desirable to generate profiles of the
      relative abundance of a multiplicity of protein species. Examples include studies
      in embryonic development, immunobiology, drug responses, cancer biology,
      biomarkers, and so on. Microarray formats provide a convenient, high-throughput
      vehicle for generating such profiles, and the repertoire of proteins that can be
      measured is growing continuously as larger panels of specific antibodies become
      available. Here we describe methods for the use of antibody microarrays, whereby
      the detection of specifically bound antigens is enhanced by rolling circle
      amplification (RCA). RCA-enhanced protein detection on antibody microarrays
      provides a means for rapid protein profiling at high sensitivity. The set of RCA
      reagents remains unchanged for different microarray formats and compositions, and
      signal readout is performed using standard fluorescent dyes and scanners. The
      method is sensitive enough for the most challenging applications, such as the
      detection of low-abundance components of human serum.

PMID- 16785640
TI  - Antibody microarrays using resonance light-scattering particles for detection.
AB  - Antibody microarray measurements show great potential for the simultaneous
      quantification of many proteins in small amounts of body fluids and extracts.
      Over the last few years, a micro-array platform centered around the concept of
      microarrays in microtiter wells was developed, and for the best assays we have
      achieved lower limits of detection in the femtomolar range using resonance light
      scattering particles for the staining of biotinylated detection antibodies.
      Although conceptually simple, these multiplexed sandwich assays are technically
      challenging. Here we describe in detail our protocols and procedures for the
      manufacturing of antibody microarrays with up to 48 different antibodies and for
      performing plasma measurements.

PMID- 16785641
TI  - Chemical proteomics profiling of proteasome activity.
AB  - Proteolysis is a key mechanism for protein homeostasis in living cells. This
      process is effected by different classes of proteases. The proteasome is one of
      the most abundant and versatile proteases, bearing three different proteolytic
      active sites. The proteasome plays an important role in essential biological
      pathways such as antigen presentation, signal transduction, and cell-cycle
      control feedback loops. The aim of this work is to design novel chemical
      strategies for capturing, detection, identification, and quantification--in one
      word, profiling--the active protease fractions of interest, in cells of different
      phenotypes. Here, a set of chemistry-based functional proteomics techniques is
      demonstrated by profiling the multi-catalytic protease activities of the
      proteasome. Importantly, functional profiling is complementary to expression
      level profiling and is an indispensable parameter for better understanding of
      mechanisms underlying biological processes.

PMID- 16785642
TI  - Two-dimensional difference gel electrophoresis.
AB  - The two-dimensional (2D) polyacrylamide gel-based approach to protein profiling
      has been successful because it is an accessible, inexpensive, and powerful tool
      for the analysis of global patterns of protein expression. All protein spots that
      are resolved and detected within the 104 to 105 dynamic range of gel capacity can
      be studied qualitatively and quantitatively in relation to each other, and viewed
      as a single image. Two-dimensional difference gel electrophoresis (DIGE) has
      strengthened the 2D platform by allowing the detection and quantitation of
      differences between samples resolved on the same gel, or across multiple gels,
      when linked by an internal standard. The technology is based on modification of
      protein extracts with fluorescent cyanine dyes, which have distinct excitation
      and emission spectra and are migration (charge and size) matched so that the same
      protein labeled with any of the dyes (Cy2, Cy3, Cy5) will migrate to the same
      position within a 2D gel, greatly enhancing reproducibility. It is becoming clear
      that each technology that is currently available for quantifying differential
      protein expression has its own weaknesses and strengths, and that multiplatform,
      integrated approaches will be necessary to provide the most complete analysis of
      any given proteome. We believe that DIGE is, and will remain in the future, a key
      front-end proteomic tool that will strongly complement other protein-profiling
      technologies.

PMID- 16785643
TI  - Oligomeric states of proteins determined by size-exclusion chromatography coupled
      with light scattering, absorbance, and refractive index detectors.
AB  - Size-exclusion chromatography (SEC), coupled with "on-line" static laser light
      scattering (LS), refractive index (RI), and ultraviolet (UV) detection, provides
      a universal approach for determination of the molar mass and oligomeric state in
      solution of native proteins as well as glycosylated proteins or membrane proteins
      solubilized in non-ionic detergents. Such glycosylated proteins or protein
      detergent complexes show anomalous behavior on SEC, thus presenting a challenge
      to determination of molar mass and oligomeric state in solution. In the SEC
      UV/LS/RI approach, SEC serves solely as a fractionation step, while the responses
      from the three detectors are utilized to calculate the molar mass for the
      polypeptide portion of the native or modified protein. The amount of sugar,
      lipid, or detergent bound to the polypeptide chain can also be estimated from the
      SEC-UV/LS/RI analysis.

PMID- 16785644
TI  - Surface plasmon resonance imaging measurements of protein interactions with
      biopolymer microarrays.
AB  - The surface-sensitive optical technique of surface plasmon resonance (SPR)
      imaging is an ideal method for the study of affinity binding interactions of
      unlabeled biological molecules in a multiplexed format. This approach has been
      widely applied to monitor DNA-DNA, DNA-RNA, peptide-protein, and protein-protein
      interactions as well as surface enzyme reactions. The success of SPR imaging
      measurements relies on the robust attachment of biomolecules in an array format.
      In this chapter, we introduce two different surface attachment chemistries that
      covalently immobilize DNA and peptides onto gold surfaces through the
      modification of self-assembled alkanethiol monolayers. Array fabrication
      approaches for the creation of individually addressable elements through the use
      of either gold dot patterns or polydimethylsiloxane (PDMS) microchannels are
      detailed. The utility of SPR imaging for the study of protein interactions is
      demonstrated with two biological systems: the binding of response regulator
      proteins, VanR and OmpR, onto a DNA array, and the interaction of S protein with
      an array of S-peptide variants. Furthermore, the application of real-time SPR
      imaging to the multiplexed determination of S-protein adsorption/desorption
      kinetics is described.

PMID- 16785645
TI  - Surface plasmon resonance mass spectrometry for protein analysis.
AB  - The combination of surface plasmon pesonance (SPR) and mass spectrometry (MS)
      provides a unique methodology for studying proteins and their interactions. SPR
      is utilized to assess protein quantitative variations and the kinetic aspects of
      protein interactions, whereas MS complements the analysis by providing an
      exclusive look at the structural features of the interacting proteins via
      measurement of their mass. Thus, intrinsic protein structural modifications that
      go unregistered via the SPR detection can readily be assessed from the MS data.
      The purpose of this chapter is dissemination of the procedures and protocols for
      successful SPR-MS analysis. The individual steps of the complete SPRMS process
      are illustrated via analysis of cardiac troponin I (cTnI).

PMID- 16785646
TI  - High-throughput affinity mass spectrometry.
AB  - Affinity mass spectrometry (AMS) is a proteomics approach for selectively
      isolating target protein(s) from complex biological fluids for mass spectrometric
      analysis. The resulting high-content mass spectrometry (MS) data show the unique
      MS protein signatures (wild-type, posttranslationally modified, as well as
      genetically modified forms of the protein target) that are present within a
      biological sample. Information regarding such protein diversity is normally lost
      in classical proteomic or immunoassay analyses. This chapter presents a step-by
      step description of high-throughput AMS in the population proteomic screening of
      the human plasma protein cystatin C.

PMID- 16785647
TI  - Isotope-coded affinity tags for protein quantification.
AB  - An important goal in proteomics is to compare the relative amounts of different
      proteins in biological samples and to try to correlate these differences with
      changes in physiological state. The isotopecoded affinity tag technique pioneered
      in Aebersold's laboratory takes advantage of differential tagging of cysteine
      residues in proteins with stable isotopes to significantly reduce the complexity
      of peptide mixtures and increase the number of sequences that are identified in a
      single tandem mass spectrometry experiment. In this approach, two samples are
      isotopically labeled (one heavy, one light) through a reactive group that
      specifically binds to cysteine residues; the samples are combined, separated with
      chromatography, and analyzed by mass spectrometry. The results are then database
      searched and a list of hundreds of proteins and their heavy:light ratio is
      obtained.

PMID- 16785648
TI  - Proteomic analysis by multidimensional protein identification technology.
AB  - Multidimensional chromatography coupled to mass spectrometry is an emerging
      technique for the analysis of complex protein mixtures. One approach in this
      general category, multidimensional protein identification technology (MudPIT),
      couples biphasic or triphasic microcapillary columns to high-performance liquid
      chromatography, tandem mass spectrometry, and database searching. The integration
      of each of these components is critical to the implementation of MudPIT in a
      laboratory. MudPIT can be used for the analysis of complex peptide mixtures
      generated from biofluids, tissues, cells, organelles, or protein complexes. The
      information described in this chapter will provide researchers with details for
      sample preparation, column assembly, and chromatography parameters for complex
      peptide mixture analysis.

PMID- 16785649
TI  - Isolation of glycoproteins and identification of their N-linked glycosylation
      sites.
AB  - Protein glycosylation has long been recognized as a very common posttranslational
      modification. Protein glycosylation is prevalent in proteins destined for
      extracellular environments. These include proteins localized on the extracellular
      surface and those secreted to body fluids. In search of a method that has the
      potential to identify and quantify most proteins found in body fluids or the cell
      surface, we have recently developed a novel method for solid-phase extraction of
      formerly N-linked glycosylated peptides from glycoproteins. It has been shown
      that proteins secreted to body fluids or localized on the cell surface can be
      specifically enriched by this method. The technique is based on the conjugation
      of glycoproteins to a solid support using hydrazide chemistry, removal of
      nonglycosylated peptides by trypsin digestion, stable isotope labeling of
      glycopeptides, and the specific release of formerly N-linked glycosylated
      peptides via peptide-N-glycosidase. The recovered formerly N-linked glycopeptides
      are then identified and quantified by tandem mass spectrometry.

PMID- 16785650
TI  - N-glycosylation analysis using the StrOligo algorithm.
AB  - N-glycosylation of proteins is the predominant glycosylation in mammals and
      confers specific conformations, localization, and functions to proteins. High
      throughput proteomics techniques have focused on the identification of proteins
      through amino acid sequence determination, with little attention paid to their
      post-translational modification, in particular, glycosylation. High-throughput
      mass spectrometric data often contain information about glycosylation, but this
      is systematically discarded by proteomic search engines. We have developed an
      algorithm, StrOligo (for STRucture of OLIGOsaccharides), capable of automated
      analysis of oligosaccharide composition and possible structures by mass
      spectrometry. The algorithm analyzes tandem mass spectrometry (MS/MS) data in an
      automated three-step process and provides possible structures and a
      discrimination score. In the first step, the algorithm constructs a relationship
      tree of the monosaccharide moiety losses observed in the MS/MS spectrum. In the
      second step, the algorithm uses the tree to propose possible compositions and
      structures from combinations of adduct and fragment ions as well as a
      discrimination score, which reflects the fit with the experimental results.
      Finally, an interface is available to visualize the proposed structures and their
      scores. As well, the MS/MS spectrum is displayed with relevant peaks labeled for
      the proposed structure with the highest discrimination score, using a modified
      nomenclature.

PMID- 16785651
TI  - MALDI-MS data analysis for disease biomarker discovery.
AB  - In this chapter, we address the issue of matrix-assisted laser
      desorption/ionization mass spectrometry (MS) data analysis for disease biomarker
      discovery. We first give a general framework of MS data analysis, then focus on
      several key steps. After that, we show some application examples using an ovarian
      sera cancer dataset. Finally, we discuss the limitations of current approaches
      and possible future research directions.

PMID- 16785652
TI  - Using the global proteome machine for protein identification.
AB  - This chapter describes the use of an open-source, freely available informatics
      system for the identification of proteins using tandem mass spectra of peptides
      derived from an enzymatic digest of a mixture of mature proteins. The chapter
      describes the use of features of the Global Proteome Machine (GPM) interface that
      assist in making comprehensive assignments between spectra and sequences,
      including the detection of point mutations, posttranslational modifications, and
      experimental artifacts. The use of this interface to validate results using the
      GPM Database is also described. This data repository allows analysts to compare
      their own results to those obtained by other scientists to determine the degree
      to which their data are consistent with previous measurements.

PMID- 16785653
TI  - Another probable case of variant CJD announced in Ireland.

PMID- 16785654
TI  - Outbreak of rubella in the Madrid region, Spain, 2005.

PMID- 16785655
TI  - World Health Organization finds no evidence that human influenza (H5N1)
      infections are spreading readily among humans in Vietnam.

PMID- 16785656
TI  - Recommendation for annual HIV and STI testing in MSM introduced in Norway.

PMID- 16785657
TI  - Isolation of Clostridium difficile ribotype 027, toxinotype III in the
      Netherlands after increase in C. difficile-associated diarrhoea.

PMID- 16785658
TI  - New legislation in Norway targets prevention of legionnaires disease.

PMID- 16785659
TI  - New Norwegian legionella legislation is consistent with the European guidelines.

PMID- 16785660
TI  - First confirmed case of lymphogranuloma venereum (LGV) in Switzerland.

PMID- 16785661
TI  - WHO status paper on prisons, drugs and harm reduction.

PMID- 16785662
TI  - Human trichinellosis in Lithuania, 1990-2004.

PMID- 16785663
TI  - International outbreak of Salmonella Stourbridge infection in Europe recognised
      following Enter-net enquiry, June-July 2005.

PMID- 16785664
TI  - Cases of Salmonella Stourbridge infection in France, April-June 2005.

PMID- 16785665
TI  - Outbreak of Salmonella Worthington infections in elderly people due to
      contaminated milk powder, France, January-July 2005.

PMID- 16785666
TI  - Larger than usual increase in cases of hantavirus infections in Belgium, France
      and Germany, June 2005.

PMID- 16785667
TI  - UK blood donors identified as at increased risk of vCJD are to be notified of
      their status.

PMID- 16785669
TI  - Increase in reported syphilis infections in Scotland in 2004.

PMID- 16785670
TI  - Measles outbreaks in Hessen and Bavaria, Germany, 2005.

PMID- 16785671
TI  - Syphilis in Germany, 2004: diagnoses increasing, particularly in smaller cities
      and rural areas.

PMID- 16785672
TI  - Large decrease in incidence of invasive Haemophilus influenzae b disease
      following introduction of routine vaccination in the Czech Republic.

PMID- 16785673
TI  - Death from rabies in a UK traveller returning from India.

PMID- 16785675
TI  - First case of vCJD reported in Spain.

PMID- 16785676
TI  - MRSA infections increasing in the Nordic countries.

PMID- 16785677
TI  - Young people's knowledge of sexually transmitted infections and condom use
      surveyed in England.

PMID- 16785679
TI  - E-alert 9 August: over 2000 cases so far in Salmonella Hadar outbreak in Spain
      associated with consumption of pre-cooked chicken, July-August, 2005.

PMID- 16785680
TI  - Highly pathogenic avian influenza reported in Russian bird populations.

PMID- 16785682
TI  - Modelling study suggests pandemic influenza could be controlled at source.

PMID- 16785681
TI  - International outbreak of Salmonella Stourbridge infection, April- July 2005:
      results of epidemiological, food and veterinary investigations in France.

PMID- 16785683
TI  - Healthcare workers could bring community-acquired MRSA from the US to Europe.

PMID- 16785684
TI  - Varicella in Romania: epidemiological trends, 1986-2004.

PMID- 16785685
TI  - Highly pathogenic avian influenza reported to be spreading into western Russia.

PMID- 16785686
TI  - Cluster of E. coli O157 infections in Scottish tourists returning from southwest
      Turkey, July-August 2005.

PMID- 16785687
TI  - First isolation of vaccine-derived poliovirus in Slovakia.

PMID- 16785688
TI  - Pertussis outbreak in recently vaccinated children in a kindergarten in Ljubljana
      during a resurgence in pertussis incidence.

PMID- 16785689
TI  - UK proposed guideline on management of severe malaria in children should trigger
      creation of European guideline.

PMID- 16785690
TI  - Increased hantavirus infections in Luxembourg, August 2005.

PMID- 16785691
TI  - Human bocavirus found in children with lower respiratory tract infection.

PMID- 16785693
TI  - Clinical experiences of the infections caused by extended-spectrum beta-lactamase
      producing Serratia marcescens at a medical center in Taiwan.
AB  - CTX-M-3 has become the most common extended-spectrum beta-lactamase (ESBL)
      produced by Serratia marcescens in Taiwan. An expanded effort to detect ESBL
      among 123 nonrepetitive isolates of S. marcescens was made and 15 (12%) ESBL
      producers were identified, all revealing CTX-M-3. Without routinely detecting the
      ESBL for S. marcescens in clinical laboratories, 80% of the ESBL-producers were
      reported to be susceptible to cefepime. The clinical spectrum of ESBL-producing
      S. marcescens-related infections included febrile urinary tract infection (n =
      3); afebrile pyuria (n = 2); pneumonia (n = 3); spontaneous bacterial peritonitis
      (n = 3); secondary bacteremia (n = 2) and one each with primary bacteremia and
      colonization of the central catheter tip. Overall, the 30-day mortality rate was
      33.3% (5/15) and the outcome depended on the severity of the underlying disorder
      and infection per se. In conclusion, although our case numbers were limited, due
      to the substantial incidence and associated mortality of ESBL-producing S.
      marcescens and its potential treatment failure by an apparently susceptible
      cephalosporin, we recommend that the detection and report of ESBL production for
      S. marcescens in clinical laboratories be made mandatory.

PMID- 16785694
TI  - Nosocomial outbreak of ceftazidime-resistant Serratia marcescens strains that
      produce a chromosomal AmpC variant with N235K substitution.
AB  - Serratia marcescens is a Gram-negative bacterium that is often associated with
      nosocomial infections. Here we analyzed the resistance mechanism of the
      ceftazidime-resistant S. marcescens nosocomial strains. The five S. marcescens
      urinary tract infection-associated isolates were positive for chromosomal ampC
      and bla(TEM-1). Four of the five strains, ES11, ES31, ES42, and ES46, were single
      clone and ceftazidime resistant. The fifth strain, ES71, was susceptible to
      ceftazidime. Analysis of the deduced amino acid sequence revealed a Glu-235-Lys
      substitution in the third amino acid of the third motif of AmpC from both ES46
      and ES71, and a site-directed mutagenesis experiment confirmed that this
      substitution is involved in the ceftazidime resistance phenotype. However, the
      resistance phenotypes of strains ES46 and ES71 to ceftazidime were quite
      different from one another, indicating that another mechanism, in addition to the
      AmpC mutation, is also involved in the determination of the resistance phenotype
      of these strains. Basal AmpC activity was more than two times higher in strain
      ES46 than in ES71, which could result in the differing resistance phenotypes of
      these two strains. The clinical significance and prevalence of extended-spectrum
      cephalosporin-resistant S. marcescens strains harboring the mutated chromosomal
      ampC gene are unclear in Japan and remain to be elucidated.

PMID- 16785695
TI  - Presentation of childhood brucellosis in Western Greece.
AB  - The purpose of this study was to evaluate clinical and laboratory findings,
      treatment modalities and final outcomes of brucellosis in children and to compare
      our data with those of other studies performed in Greece. Fifty-two children
      treated for brucellosis in the Department of Pediatrics during the decade 1995
      2004 were analyzed. Of the 52 children, 47 were reexamined during July 2005.
      Fever, arthritis or arthralgia, hepatomegaly and splenomegaly were the main
      findings. Young children had positive blood cultures and lower or negative
      antibody titers statistically significantly more often than did older children.
      Brucella abortus was isolated in 9 of 18 patients with positive blood cultures.
      Antibiotic treatment lasted for 28 days on average. There were no complications
      or relapses, except one, and the final outcomes were excellent.

PMID- 16785696
TI  - The predictive value of serum procalcitonin levels in adult patients with active
      pulmonary tuberculosis.
AB  - The aim of our prospective study was to evaluate the predictive value of serum
      procalcitonin (PCT) level in comparison with C-reactive protein level and
      erythrocyte sedimentation rate for the diagnosis of pulmonary tuberculosis (PTB)
      on admission and 6 months after the administration of anti-tuberculous
      chemotherapy (ATCT). Seventy-five adult male patients with active PTB who were
      mycobacteriologically diagnosed (smear and culture positivity) were examined in
      this study. As a control group, 75 healthy adult males were enrolled. The
      measured serum PCT levels were within the normal range both in healthy
      individuals and in patients 6 months after ATCT. Serum PCT levels had been
      slightly high on admission in patients with PTB in comparison with controls (P =
      0.01) and patients who had ATCT (P = 0.001), and this difference was
      statistically significant, but the PCT levels of most cases with PTB (58.7%) were
      below the usual cut-off level (0.5 ng/mL). We conclude from this study that the
      serum PCT level was not a reliable indicator in the diagnosis of active PTB
      because of its low sensitivity (41.3%), and in most cases it was not capable of
      overcoming the cut-off level even if statistically meaningful results were
      obtained. The PCT test for the presumptive diagnosis of PTB cannot be substituted
      for microbiological, epidemiological, clinical and radiological data.

PMID- 16785697
TI  - Cost-effectiveness analysis of antiretroviral drug treatment and HIV-1
      vaccination in Thailand.
AB  - The prevalence of adult HIV/AIDS in Thailand is declining due to intense
      prevention strategies, but it still continues to be a critical health problem
      with a prevalence of 1.5%. Several HIV vaccine candidates for the prevention of
      HIV infection or progress to AIDS were examined in clinical trials. We evaluated
      the cost-effectiveness of a vaccination regimen (rBCG prime-rDIs boost) currently
      in its pre-clinical phase. The cost-effectiveness of three interventions
      (vaccination, highly active antiretroviral treatment [HAART], and the combination
      of the two) through an existing vaccination program was assessed in a Markov
      model. The disability-adjusted life year (DALY) was the main effectiveness
      measure. In the base case the efficacy of the vaccine for preventing HIV
      infection was assumed to be 30%. The cost of the vaccine was estimated on the
      basis of its predicted production capacities in Thailand. The incremental cost
      effectiveness ratios of vaccination, HAART, and the combination were about dollar
      US 75, dollar US 610, and dollar US 267 per DALY averted compared with the do
      nothing strategy in the base case. The HAART-only strategy seemed to be less cost
      effective than the other options under the current assumptions. Sensitivity
      analyses indicated that the new HIV infection rate and the vaccine efficacy could
      affect the results.

PMID- 16785699
TI  - Masks for influenza patients: measurement of airflow from the mouth.
AB  - In case of a new influenza pandemic, provision of masks to coughing patients
      could be used to slow expansion of the epidemic. To quantitatively assess the
      efficacy of different masks, we used an ultrasonic anemometer to measure the
      velocity of airflow from the mouth in coughing. We found that even the cheapest
      paper masks reduced the air speed to less than 1/10, implicating their
      effectiveness in decreasing viral spread. We therefore propose that governments
      provide free masks to coughing patients in the general population upon the
      emergence of a new human influenza virus.

PMID- 16785698
TI  - Cholera outbreak in southeast of iran: routes of transmission in the situation of
      good primary health care services and poor individual hygienic practices.
AB  - Within the years 2001 to 2004 Sistan-va-Baluchestan was the only province with
      transmission of cholera in Iran. The objective of this study was to determine the
      epidemiological characteristics of the cholera outbreak that occurred in 2004 in
      the Sarbaz district in the southern parts of this province. The surveillance data
      were analyzed, and a matched case-control study was performed. From 22 October to
      15 November 2004, from 2,242 diarrhea cases that were sampled for stool culture,
      90 cases were positive for Vibrio cholerae O1 El-Tor biotype, serotype Ogawa.
      Multivariate analysis showed that risk factors for cholera were drinking
      beverages from street vendors (OR = 10.16, 95% CI: 2.55 - 40.50), illiteracy (OR
      = 5.76, 95% CI: 2.63 - 30.09), no hand washing with soap after toilet use (OR =
      22.06, 95% CI: 2.91 - 167.11), no hand washing with soap before meals (OR = 3.64,
      95% CI: 1.03 - 12.82), sex (OR = 3.73, 95% CI: 1.17 - 11.89) and eating food left
      over from previous meals without reheating (OR = 4.03, 95% CI: 1.23 - 13.18). The
      source of drinking water showed weak association with cholera only in univariate
      analysis (OR = 2.83, 95% CI: 1.12 - 7.19). The development of primary health
      care, even though it can improve the conditions that control the spread of an
      epidemic, is not enough of a control measure as long as the social hygienic
      standards are low and people do not follow the basic personal hygiene
      regulations.

PMID- 16785700
TI  - Surveillance of group B streptococcal toxic shock-like syndrome in nonpregnant
      adults and characterization of the strains in Japan.
AB  - Nine group B streptococci (GBS) strains were isolated from five toxic shock-like
      syndrome cases of nonpregnant adults in Japan from 2001 to 2005. All of them were
      identified as Streptococcus agalactiae. The serotypes of these strains were Ib,
      III, V, and VII. Pulsed-field gel electrophoresis revealed that the patterns of
      the strains isolated from the different patients were variable. Antimicrobial
      susceptibility tests showed that all of the strains were susceptible to
      penicillin G, ampicillin, cefotaxime, clindamycin, and telithromycin. One strain
      showed intermediate resistance to erythromycin.

PMID- 16785701
TI  - Serum levels of sICAM-1 and sE-selectin in patients with dengue virus infection.
AB  - The purpose of this study was to measure the serum level of sICAM-1 and sE
      selectin as markers for endothelial damage in patients with dengue fever (DF) and
      dengue hemorrhagic fever (DHF). Twenty-nine patients with serologically-proven
      dengue virus infection (age 10.6 +/- 2.4 years, 55% male, DF = 13 and DHF = 16)
      were enrolled. Serum samples were collected from 25 healthy children (age 10.6 +/
      2.3 years, 40% male) as the control group. A follow-up was done at a mean
      interval of 15.9 +/- 1.6 days. The level of sICAM-1 at the toxic stage was
      significantly elevated compared to its level at the follow-up (494.1 +/- 107.4
      versus 358.2 +/- 67.6 ng/ml, P = 0.001), but no difference was found between
      patients with DF and patients with DHF (444.1 +/- 158.0 versus 465.1 +/- 154.6
      ng/ml, P = 0.74). The sICAM-1 level at the follow-up was similar to that of the
      control group (396.9 +/- 113.0 ng/ml, P = 0.56). The level of sE-selectin at the
      toxic stage was not different from its level at the follow-up (75.9 +/- 33.0
      versus 75.5 +/- 31.7 ng/ml, P = 0.96), and no difference was found between the DF
      group and the DHF group (64.1 +/- 25.7 versus 78.8 +/- 39.9 ng/ml, P = 0.30).
      These levels were not elevated compared to the sE-selectin level that was
      determined in 8 patients in the control group (94.7 +/- 20.5 ng/ml, P = 0.12). In
      conclusion, there is evidence of endothelial activation by an increased sICAM-1
      level in patients with dengue virus infection. However, the degree of endothelial
      activation alone may be similar for patients with DF and patients with DHF, and
      this fact by itself cannot explain the difference between the two clinical
      syndromes of dengue virus infection. The sE-selectin level was not elevated for
      patients included in this study.

PMID- 16785702
TI  - Tuberculosis-like peritonitis due to an atypical Mycobacterium infection in a
      Japanese woman.
AB  - It is not known whether atypical Mycobacterium (AM) causes peritonitis in humans.
      We described a case of tuberculosis-like peritonitis caused by an AM. Genetic
      analysis of the biopsy specimens suggested an AM infection. Thus, we concluded
      that peritonitis in humans can be caused by some AM species as well as by
      Mycobacterium tuberculosis complex.

PMID- 16785703
TI  - Characterization of erythromycin resistance of Streptococcus pyogenes isolated
      from pharyngitis patients in Korea.
AB  - Six hundred fifteen isolates of Streptococcus pyogenes were collected over a 6
      year period from patients with pharyngitis in Korea. All isolates were
      characterized in terms of their antibiotic resistance, the phenotypes of
      erythromycin resistance, the frequencies of erm(B), erm(A), and mef(A) genes, and
      the emm genotype. The prevalent emm genotypes were emm12 and emm4. Moreover, the
      emm12 genotype was found to be the most resistant strain to erythromycin. Among
      the 126 strains demonstrating resistance to erythromycin, those with erm(B) were
      the most prevalent, accounting for 64.3% of the total. In summary, it is
      suggested that the S. pyogenes pathogen isolated from pharyngitis patients in
      Korea developed resistant gene acquisition, as well as a resistant phenotype,
      according to the annual prevailing emm type. It is also suggested that the emm
      genotype distribution of erythromycin-resistant strains is correlated to the
      acquisition of resistant genes.

PMID- 16785704
TI  - The low rate of methicillin-resistant Staphylococcus aureus in Turkish children.
AB  - During a 6-month period, swab samples were obtained from the nares, axilla and
      perineum of 1,000 children, age 0 to 16 years, who were attending a pediatric
      outpatient clinic. Staphylococcus aureus was isolated in 173 of the children.
      Only one child, a 35-day-old boy who had remained at the neonatal intensive care
      unit for 1 week after birth, was identified as a carrier of methicillin-resistant
      S. aureus. Except in diagnosed cases of allergic rhinitis, potential predisposing
      factors for colonization with S. aureus in our sample were comparable to those in
      non-colonized children.

PMID- 16785705
TI  - Frequency of amantadine-resistant influenza A virus isolated from 2001-02 to 2004
      05 in Nara Prefecture.
AB  - We investigated the frequency of amantadine-resistant influenza A viruses in Nara
      Prefecture during four epidemic seasons from 2001-02 to 2004-05. Point mutations
      within the M2 gene were identified using RT-PCR and DNA sequencing analysis. Five
      viruses (3.4%) with point mutation were observed from 145 strains analyzed. Three
      viruses (2.0%) possessed a change at position 31 (AGT-->AAT, Ser to Asn), one
      virus (0.7%) showed a change at position 26 (CTT-->TTT, Leu to Phe), one virus
      (0.7%) showed a change at position 27 (GTT-->ATT, Val to Ile), and none showed a
      change at position 30. All of these changes were the transition type of mutation.
      These results indicated that the possible circulation of drug-resistant viruses
      to the community was not supported by the findings obtained during the 2004-05
      season in Nara.

PMID- 16785706
TI  - Rapid subtyping of influenza a virus by loop-mediated isothermal amplification:
      two cases of influenza patients who returned from Thailand.

PMID- 16785707
TI  - Epidemiology and molecular analysis of group A streptococci from patients
      involved in food-borne disease outbreaks in Japan between 1996 and 2003.

PMID- 16785708
TI  - Epidemiological study of Japanese spotted fever and tsutsugamushi disease in
      Shimane Prefecture, Japan.

PMID- 16785709
TI  - A food-borne norovirus outbreak at a primary school in Wakayama Prefecture.

PMID- 16785710
TI  - Scrub typhus (tsutsugamushi disease) in Kanagawa Prefecture in 2001-2005.

PMID- 16785711
TI  - Sequence characteristics of HA gene in influenza type A (H1N1) virus isolated
      during the 2005-2006 season in Aichi Prefecture, Japan.

PMID- 16785712
TI  - Dual infection by dengue virus and Plasmodium vivax in Alappuzha District,
      Kerala, India.

PMID- 16785713
TI  - Characterization of biological activities of Brucella melitensis
      lipopolysaccharide.
AB  - Biological activities of lipopolysaccharide (LPS) from Brucella melitensis 16M
      were characterized in comparison with LPS from Escherichia coli O55. LPS
      extracted from B. melitensis was smooth type by electrophoretic analysis with
      silver staining. The endotoxin-specific Limulus activity of B. melitensis LPS was
      lower than that of E. coli LPS. There was no significant production of tumor
      necrosis factor-alpha and nitric oxide in RAW 264.7 macrophage cells stimulated
      with B. melitensis LPS, although E. coli LPS definitely induced their production.
      On the other hand, B. melitensis LPS exhibited a higher anti-complement activity
      than E. coli LPS. B. melitensis LPS as well as E. coli LPS exhibited a strong
      adjuvant action on antibody response to bovine serum. The characteristic
      biological activities of B. melitensis are discussed.

PMID- 16785714
TI  - First record of Leptospira borgpetersenii isolation in the Amami Islands, Japan.
AB  - In 2003, a Leptospira survey was performed on Yoroshima Island of the Amami
      Islands located in the southwestern part of Japan. Seven Leptospira strains were
      isolated from the field rat Rattus rattus, which were identified as L.
      borgpetersenii by flaB sequencing, 16S rDNA sequencing and gyrB sequencing, and
      serovar Javanica was determined by a microscopic agglutination test. NotI-long
      restriction fragment analysis indicated that these isolates were genetically
      indistinguishable from an isolate from the Okinawa Islands. The present results
      suggest that L. borgpetersenii is migrating into the Amami Islands in Japan.

PMID- 16785715
TI  - Two different conformations of rabies virus glycoprotein taken under neutral pH
      conditions.
AB  - We previously reported that the rabies virus glycoprotein (G) takes either of two
      different conformations (referred to as B and C forms) under neutral pH
      conditions, that could be differentiated by their reactivity to a monoclonal
      antibody (mAb), #1-30-44, that recognizes the acid-sensitive conformational
      epitope, and the formation taken is dependent on two separate regions containing
      Lys-202 and Asn-336 of the protein (Kankanamge et al., Microbiol. Immunol., 47,
      507-519, 2003). Semi-quantitative antibody-binding assays demonstrated that only
      one-third to one-fourth of mature G proteins on the cell surface were taking the
      1-30-44 epitope-positive B form even at pH 7.4. The ratio of B to C varied,
      depending on the environmental pH, but did not decrease to zero even at pH 5.8
      6.2, preserving a certain content (about 15-20%) of B form. Immunoprecipitation
      studies demonstrated that a portion of G proteins were intimately associated with
      a dimer form of matrix (M) protein in terms of resistance to treatment with a
      mixture of 1% deoxycholate and 1% Nonidet P-40, and seemed to preserve the B form
      even at lower pHs. Similar results were also obtained with the virion-associated
      G proteins, including the intimate association of a portion of the G proteins
      with the M protein dimer. From these results, we assume that a certain portion of
      the rabies virion-associated G proteins are associated with a dimer form of M
      protein, keeping the 1-30-44 epitope-positive B conformation under various pH
      conditions, which might possibly assure the virion's recognition of host cell
      receptor molecules in the body.

PMID- 16785716
TI  - Prevalence of low positive anti-HCV antibodies in blood donors: Schistosoma
      mansoni co-infection and possible role of autoantibodies.
AB  - Patients infected with schistosoma frequently show a high seroprevalence of anti
      hepatitis C virus (anti-HCV) antibodies. The aim of this study was to find the
      underlying reason for this phenomenon, and to examine a possible involvement of
      autoantibodies. Out of 2,400 Egyptian blood donors, 192 (8%) were anti-HCV
      positive by ELISA. They were 133 males and 59 females with age ranging from 27 to
      48 years. According to optical density ratio (ODR) of anti-HCV antibodies, 96
      cases were low positive (LP) with ODR (1-2) designated as group I, and 96 were
      high positive (HP) with ODR (> or =2) (group II). Both groups were examined for
      quantitative HCV core antigen (HCVcAg), liver function (Albumin, ALT, AST) and
      anti-Schistosoma mansoni(anti-Sm) IgG. Group I cases were HCVcAg negative with
      normal liver function tests, and 44 of them were anti-Sm positive. Ninety cases
      (93.75%) of group II were HCVcAg positive with markedly affected liver function
      tests and 72 cases were anti-Sm positive. All group I cases were examined for
      autoimmune markers (ANA, AMA, SMA and LKM). In group I, 33 (75%) of anti-Sm
      positive cases were positive for one or more of the autoimmune markers examined,
      while none of anti-Sm negative was positive for any marker with significant
      difference between the two groups (P < 0.0001). Our results primarily on blood
      donors indicate that LP anti-HCV frequently represents false-positive reactivity
      with a possible role of Sm-induced autoantibodies in this phenomenon.

PMID- 16785717
TI  - Beta-glucan derived from zymosan acts as an adjuvant for collagen-induced
      arthritis.
AB  - Collagen-induced arthritis (CIA) is an experimental model of rheumatoid arthritis
      (RA) and has helped researchers to analyze the pathogenesis of inflammatory joint
      disease. In classical CIA, Freund's complete adjuvant (FCA), which contains heat
      killed Mycobacterium tuberculosis, is used as an adjuvant. In our previous study,
      we reported that particles of beta-glucan, OX-CA, derived from Candida albicans,
      acted as a proper adjuvant in the CIA model. In this study, to establish pure
      beta-glucan as an adjuvant for CIA, we tested a commercially available
      preparation of Zymosan A (ZYM) and modified its products. beta-Glucan fractions
      of ZYM were prepared by oxidation with various concentrations of NaClO. The
      oxidized ZYM (OX-ZYM) was mainly composed of beta-glucan. In this study, we
      examined its effect as an adjuvant for CIA. DBA/1 mice injected with CII and OX
      CA developed arthritis 7-10 days after receiving booster injections; the OX-ZYM
      fractions induced arthritis with the same time course. 0.01% OX-ZYM (oxidized
      with a 0.01% NaClO solution) caused arthritis faster than 0.1% OX-ZYM or 0.5% OX
      ZYM. In conclusion, beta-glucan derived from ZYM by brief oxidation with NaClO is
      a suitable adjuvant for a CIA model with anti-CII antibody production.

PMID- 16785718
TI  - Unnoticed spread of class 1 integrons in gram-positive clinical strains isolated
      in Guangzhou, China.
AB  - A total of 46 gram-positive bacteria isolated from clinical specimens collected
      in China were subjected to PCR analysis with the intI1-specific primers, and the
      intI1-positive strains were further analyzed for their resistance gene cassette.
      All isolates possessed the class 1 integron in their genomes and the array of
      gene cassettes was dhfrXII-orfF-aadA2, which is very similar to other organisms
      except in one isolate carrying an additional copy of the class 1 integron
      containing the aadA2 gene cassette. Altogether, the results indicate that the
      class 1 integron is widespread in gram-positive clinical strains isolated in
      Guangzhou, China.

PMID- 16785720
TI  - Deletion polymorphisms in the promoter region of Fcgamma receptor IIB is not
      associated with antigen-specific IgG2a and IgG2b antibody responses in NC/Nga
      mice.
AB  - Fcgamma receptor (R) IIB, a low-affinity FcR for IgG, inhibits B cell Ag R (BCR)
      mediated activation when these two receptors are cross-linked by Ag and IgG
      containing immune complexs (ICs). We found deletion polymorphisms in the promoter
      region of fcgr2b in NC/Nga mice, a model for human atopic dermatitis. NC/Nga mice
      produced significantly higher levels of ovalbumin (OVA)-specific IgG, IgG2a and
      IgG2b than did BALB/c mice. Analysis of (BALB/c x NC/Nga)F1 x BALB/c or (BALB/c x
      NC/Nga) F1 x NC/Nga backcross mice revealed that deletion polymorphisms of fcgr2b
      in NC/Nga mice does not directly regulate hyper OVA-specific IgG2a and IgG2b Ab
      responses.

PMID- 16785719
TI  - Candida pseudohaemulonii Sp. Nov., an amphotericin B-and azole-resistant yeast
      species, isolated from the blood of a patient from Thailand.
AB  - Candida haemulonii(types I and II) is rarely isolated from clinical specimens. We
      isolated a strain that is phylogenetically close to C. haemulonii from the blood
      of a Thai patient, and named it C. pseudohaemulonii sp. nov. (CBS 10099T = JCM
      12453T = DMST 17134T). The new species and C. haemulonii types I and II were
      resistant to amphotericin B and azole agents but were susceptible to a 1,3-beta-D
      glucan synthetase inhibitor, micafungin, and 5-flucytosine. The species were
      easily distinguished using an ID32 yeast identification kit. The taxonomic
      description of C. pseudohaemulonii sp. nov. is presented.

PMID- 16785721
TI  - Estimation of membrane permeability and intracellular diffusion coefficients.
AB  - We propose a method for estimating membrane permeability and the intracellular
      diffusion coefficient using pulsed-gradient spin-echo measurement in combination
      with numerical simulation. The diffusion signal attenuation of leukocytes was
      measured with 4pi(2)q(2)(Delta-delta/3) values up to 6000 s/mm(2). For numerical
      simulations, the cell was modeled as a 15 x 15 microm(2) square with various
      membrane permeabilities and intracellular diffusion coefficients. Minimization of
      the difference in signal attenuations between the measurement and the simulation
      enabled estimations of these unknown parameters for the leukocytes. A cell sample
      of 2.17 x 10(8) cells/mL had a membrane permeability and an intracellular
      diffusion coefficient of 23 mum/s and 8.9 x 10(-4) mm(2)/s, respectively.

PMID- 16785722
TI  - Positive and negative predictive values of BI-RADS-MRI descriptors for focal
      breast masses.
AB  - PURPOSE: The purposes of this study were to evaluate the positive and negative
      predictive values of the BI-RADS-MR descriptors of focal masses and to develop an
      interpretation model based on the kinetic and morphologic parameters. METHODS:
      Retrospective review was performed of 171 consecutive focal breast masses. MR
      imaging was performed on a 1.5T system using the volumetric interpolated breath
      hold examination sequence (mean partition thickness, 1.2 mm; time of acquisition,
      35 s). Kinetic enhancement patterns were assessed by visually comparing signal
      intensity on the dynamic images acquired at 60 s and 4 min (washout, plateau, and
      persistent). RESULTS: There were 126 malignant and 45 benign lesions. The most
      frequent morphological finding among the malignant lesions was heterogeneous
      internal enhancement in the delayed phase (96%; P<0.001); the most frequent
      finding in benign lesions was smooth margin or smooth shape/margin (80 to 82%;
      P<0.001). The features with the highest positive predictive value for carcinoma
      were spiculated margin (100%), delayed central enhancement (100%), delayed
      enhancing internal septations (97%), and irregular shape (97%). The
      characteristics with the highest diagnostic accuracy for malignancy were
      spiculated margin (100%) and heterogeneous enhancement following washout in the
      smooth shape/margin group (100%). The sensitivity, specificity, and positive and
      negative predictive values of an interpretation model based on a combination of
      the morphologic characteristics and kinetic information were 99%, 89%, 96%, and
      98%, respectively. CONCLUSION: A combination of morphologic criteria,
      particularly lesion shape/margin and internal heterogeneity, and kinetic
      information is useful for differentiating benign and malignant lesions.

PMID- 16785723
TI  - Development of an ESR/MR dual-imaging system as a tool to detect bioradicals.
AB  - A system combining electron spin resonance imaging (ESRI) with another imaging
      modality capable of enabling visualization of the distribution of bioradicals on
      an anatomical map of the specimens would be a superior biomedical imaging system.
      We describe the development of an ESR/MR dual-imaging system with one permanent
      magnet and the biomedical applications of this system. The magnetic circuit
      developed for the ESR/MR dual-imaging system consisted of the permanent magnet
      made of Fe-Nd-B, pole pieces, and poke. The permanent magnet was installed on the
      MR side only, and the ESR side was made of pole pieces only. The magnetic field
      was adjusted to 0.5T at MR and to 0.042T at ESR. The overall dimensions of the
      magnet developed for the ESR/MR imaging system were 460 (W)x440 (D)x460 (H) mm,
      and it weighed 220 kg. The distance of each center for the magnet for ESR and MR
      imaging could be set as close as 200 mm. The entire ESR/MR imaging system can be
      installed in a common laboratory without magnetic shielding. MR images of plants
      (myoga) and small animals (mice and rats) were successfully acquired with or
      without ESR operation. ESR spectra of nitroxyl spin probes were also measured,
      even with MRI operation. ESR signals of triarylmethyl derivatives with narrow
      line-width (0.026 mT) were observed in living mice while MRI was operating. The
      ESR/MR imaging dual functions work properly with no electric or magnetic
      interference. The ESR/MR dual images demonstrate that this system enables
      visualization of the distribution of bioradicals on the anatomical map of the
      object.

PMID- 16785724
TI  - Diagnosis of ectopic pregnancy with MRI: efficacy of T2*-weighted imaging.
AB  - PURPOSE: To assess MRI in diagnosing ectopic pregnancy (EP), emphasizing T(2)*
      weighted imaging (WI) efficacy. METHODS AND MATERIALS: This is a prospective
      study of 24 female patients (16 to 41 years, average 29.9) clinically suspected
      of EP from April 1999 to June 2001. Eighteen had minimal vaginal bleeding and
      slight abdominal pain. All had positive pregnancy tests, and sonography showed no
      intrauterine pregnancy despite estimated gestational age of embryos and/or high
      concentrations of human chorionic gonadotrophin. MRI was performed with a 1.5T
      imager (Siemens, Vision VB33A) with a body-array coil. T(2)-WI (HASTE), T(1)-WI
      (2D FLASH), and T(2)*-WI (2D FLASH) were obtained without contrast. T(2)-WI was
      routinely obtained in 3 directions. T(2)*-WI orientation was determined based on
      the T(2)-WI. One of 4 radiologists with experience interpreting abdominal MR
      images interpreted images based on transvaginal ultrasonography (TVUS) and
      laboratory results. Abnormal adnexal mass with remarkable low signal area on
      T(2)*-WI was diagnosed as EP. RESULTS: We diagnosed 19 cases as EP. Tubectomy in
      eighteen and abdominal total hysterectomy in one confirmed diagnosis. In one
      undergoing diagnostic laparoscopy, EP was denied. In 5 cases diagnosed negative
      based on the above criterion, no mass was detected in three, and no area of low
      signal was recognized on T(2)*-WI in the masses in two. EP was denied in four of
      five, and in one of the five, who underwent tubectomy, EP without bleeding was
      diagnosed. All EP were tubal pregnancies at final diagnosis, 19 were ampullar
      pregnancies and one, interstitial. Using MRI to diagnose EP, with T(2)*-WI as a
      key diagnostic factor, sensitivity was 95%, specificity 100%, and accuracy 96%.
      CONCLUSIONS: MRI using T(2)*-WI is a sensitive, specific, and accurate method to
      evaluate EP. T(2)*-WI is highly accurate for detecting and diagnosing EP because
      of its sensitivity to fresh hematoma.

PMID- 16785725
TI  - Efficacy of cardiac MRI in the evaluation of ischemic heart disease.
AB  - With the development of fast scan techniques and technical advances in software,
      cardiac MRI can now be used for morphological and functional evaluation of the
      heart with good reliability and high spatial and temporal resolution. Cardiac MRI
      is employed at many institutions, mainly for assessing ischemic heart disease.
      Cardiac MRI can be used to identify coronary artery stenosis, evaluate myocardial
      viability, assess left ventricular wall motion and function, measure coronary
      blood flow and flow reserve, and obtain other useful information for the
      diagnosis of ischemic heart disease in a single examination, serving as a true
      comprehensive cardiac study. With regard to the evaluation of coronary artery
      stenosis, new techniques, such as whole-heart coronary MRA, permit visualization
      of the coronary arteries to their peripheral branches without contrast agent.
      Good results have been reported for whole-heart MRA as compared with X-ray
      coronary angiography (CAG). Attempts to evaluate plaque characteristics by
      visualizing the walls of the coronary arteries have also been reported recently.
      Technical improvements have been made in myocardial perfusion MRI to detect
      myocardial ischemia and in delayed contrast-enhanced MRI to assess myocardial
      viability, and some researchers have recently reported that the diagnostic
      capabilities of these techniques match or surpass those of cardiac nuclear
      medicine studies. We outline the features of the latest MR imaging techniques for
      the diagnosis of ischemic heart disease, discuss their practical applications,
      and compare them with other imaging modalities.

PMID- 16785726
TI  - MR findings of cerebral white matter in Cockayne syndrome.
AB  - The characteristic magnetic resonance (MR) findings of Cockayne syndrome have
      been reported; however, the corresponding characteristics on diffusion-weighted
      and fluid-attenuated inversion recovery (FLAIR) imaging are yet to be documented.
      In this adult case with Cockayne syndrome, we identified small patchy subcortical
      lesions visualized as areas of high intensity on diffusion-weighted images and
      low intensity on FLAIR images. It is possible that these findings reflect active
      demyelinating lesions.

PMID- 16785727
TI  - Mesoblastic nephroma: a case report of prenatal detection by MR imaging.
AB  - We report a case of mesoblastic nephroma detected prenatally by magnetic
      resonance (MR) imaging. MR imaging could provide valuable information about the
      origin and nature of a fetal abdominal mass and help define the relationship of
      the mass to adjacent structures.

PMID- 16785728
TI  - Fenestration of the middle cerebral artery detected by MR angiography.
AB  - Unlike fenestration of the posterior cerebral arterial circulation, fenestration
      of the anterior cerebral arterial circulation has not been well described. We
      investigated the location and configuration of fenestration of the middle
      cerebral artery (MCA) detected by magnetic resonance (MR) angiography. We found 6
      fenestrations of the MCA among cranial MR angiography images obtained from about
      2,000 patients during the past 9 years at our institution using either of two
      1.5T imagers. All images were obtained by the three-dimensional time-of-flight
      technique. Maximum-intensity projection images in the horizontal rotation view
      were displayed stereoscopically. All 6 fenestrations had small slit-like
      configurations, five located at the proximal M1 segment, the other, at the middle
      M1 segment. No associated aneurysm was found. Although MCA fenestration is
      extremely rare and cerebral artery fenestration usually has no clinical
      significance, an aneurysm can arise at the proximal end of the fenestration.
      Thus, recognizing MCA fenestration is important when interpreting cranial MR
      angiograms.

PMID- 16785730
TI  - Effects of omega-3 fatty acids on acute necrotizing pancreatitis in rats.
AB  - The aim of this study was to investigate the influence of omega-3 fatty acids
      (omega3FA) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic
      acid in rats. The induction of ANP resulted in significant increases in mortality
      rate, intestinal permeability, bacterial infection in pancreas and
      extrapancreatic organs, and serum activity of urea and amylase, alanine
      transferase (ALT), interleukin (IL)-6, tumor necrotizing factor-alpha (TNF
      alpha), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, tissue
      activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and
      lung, and a considerable decrease of concentrations of calcium, protein and
      albumin. The use of omega3FA reduced mortality, phenol sulfophthalein excretion
      in urine, bacterial infection in pancreas, liver, spleen, MPO and MDA levels in
      pancreatic and lung tissue, LDH level in BAL fluid and serum IL-6 and TNF-alpha
      values. Serum triglyceride increased only in the omega3FA groups. Serum amylase,
      ALT, calcium, urea, protein, IL-1, and degree of pancreatic damage indicated no
      difference between the pancreatitis groups. Increased intestinal permeability and
      cytokine levels, and free radical damage play an important role during the course
      of acute pancreatitis. The treatment with omega3FA improves these effects.
      omega3FA may be useful in the treatment during ANP in rats. Therefore, it can be
      beneficial in patients with pancreatitis.

PMID- 16785729
TI  - Primary repair of esophageal atresia in extremely low birth weight infants: a
      single-center experience and review of the literature.
AB  - BACKGROUND: Advances in neonatal intensive care have led to an increased survival
      of very low birth weight (VLBW, <1,500 g) and extremely low birth weight infants
      (ELBW, <1,000 g). Several abnormalities may occur in these children, e.g.
      esophageal atresia (EA), imperforate anus or abdominal wall defects. Correction
      of EA is often performed as a staged procedure in this group of patients.
      OBJECTIVES: To evaluate the feasibility of a primary correction of EA in 4 ELBW
      and VLBW infants. METHODS: Between 2002 and 2004, 4 infants below 1,200 g were
      operated on in our institution with a diagnosis of EA with lower
      tracheoesophageal fistula. Birth weight ranged from 780 to 1,120 g (median: 920
      g), gestational age from 28 to 30 weeks. Treatment included closure of the
      tracheoesophageal fistula and primary anastomosis of the esophagus in a one-step
      procedure. RESULTS: Primary correction of EA and fistula repair was feasible in
      all children. Initially, all children had a normal passage of the esophagus as
      observed in barium swallowing. One child suffering from a leakage of the
      anastomosis was managed conservatively. Another infant suffered from spontaneous
      small bowel perforation 6 days after surgery, which was treated by laparotomy.
      One child developed stenosis of the esophagus and required a single dilatation 14
      months after initial treatment. In the 4th child, a type II cleft syndrome was
      subsequently diagnosed, requiring secondary cleft repair together with
      semifundoplication. This child eventually died from cytomegalovirus pneumonia.
      CONCLUSIONS: Primary repair of EA and closure of a tracheoesophageal fistula is
      technically feasible and offers a good treatment option for ELBW and VLBW
      infants. Staged repair can be avoided. Infants with cleft syndrome are still a
      diagnostic and therapeutic challenge.

PMID- 16785731
TI  - Effect of proton pump inhibitors on hepatic regeneration.
AB  - INTRODUCTION: The liver is critical in multiple processes, including the
      clearance of endogenous compounds, the synthesis of macromolecules, and organ
      specific biotransformation processes. Therefore, the liver's regenerating
      capacity is of vital importance. Multiple pathways are activated in the complex
      process that leads to hepatic regeneration. In the present study, we aimed to
      evaluate the effect of proton pump inhibitors omeprozole, lansoprazole, and
      pantoprazole on hepatic regeneration following partial hepatectomy. MATERIALS AND
      METHODS: Four groups were formed with 32 rats in each. Partial liver resections
      were performed for all animals. Omeprazole (71.4 microg/day), lansoprazole (107
      microg/day), pantoprazole (143 microg/day) and placebo (0.5 cm(3)) were
      administered to the groups respectively. A quarter of the rats in each group were
      sacrificed on the 1st postoperative day. The rest were sacrificed on the 3rd, 5th
      and 7th postoperative days. The remnant regenerating liver mass was removed and
      weighed, and Ki-67 monoclonal antibody levels were measured. RESULTS: There was
      no statistical difference between the four groups on the first day in evaluating
      the weight of the liver mass (p = 0.09) and Ki-67 (p = 0.268) levels. Only the
      omeprazole group showed a difference; the Ki-67 level was lower in the omeprazole
      group on the 3rd (p = 0.003, p = 0.0001, p = 0.003), 5th (p = 0.017, p = 0.001, p
      = 0.0001) and 7th (p = 0.0001) days compared to the other groups. Also the weight
      of the remnant liver mass was lower in the omeprazole group on the 3rd, 5th and
      7th (p = 0.0001) days. CONCLUSION: We figured out that lansoprazole and
      pantoprazole have no effects on liver regeneration, whereas omeprazole showed a
      negative effect on hepatic regeneration.

PMID- 16785732
TI  - Intestinal duplications--experience in 6 cases.
AB  - Intestinal duplications are rare congenital anomalies, and most of them are
      detected in the first 2 years of life or antenatally. The clinical presentation
      depends on location, size, and the presence of ectopic gastric mucosa. Ultrasound
      scans during pregnancy result in a higher rate of antenatally detected
      duplications which allows early treatment and avoidance of possible
      complications. Resection of the duplication without adjacent bowel should be the
      treatment of choice. En bloc resection or partial excision with mucosectomy is
      advised in some cases. We present our experience with 6 patients treated in our
      institution from February 2002 to October 2005.

PMID- 16785733
TI  - Preclinical comparison of mTHPC and verteporfin for intracavitary photodynamic
      therapy of malignant pleural mesothelioma.
AB  - Efficacy and tumour selectivity of photodynamic therapy with two clinically
      approved sensitizers (mTHPC, verteporfin) were assessed for focal intracavitary
      photodynamic therapy (PDT) in rodents with malignant pleural mesothelioma (MPM)
      at recommended drug-light conditions and at escalating sensitizer dosages. MPM
      tumours were generated in 15 Fischer rats by subpleural mediastinal tumour cell
      injection followed after 5 days by intracavitary PDT with light delivery
      monitored by in situ dosimetry. Animals were intravenously sensitized either with
      mTHPC (0.1 mg/kg, n = 3; 0.2 mg/kg, n = 3) followed after 4 days by illumination
      with 20 J/cm(2) at 652 nm, or with verteporfin (0.6 mg/kg, n = 3; 1.2 mg/kg, n =
      3) followed after 20 min by illumination with 100 J/cm(2) at 689 nm. Three
      untreated tumour-bearing animals served as controls. Histological evaluation of
      the treated tumour and of adjacent normal organs was performed 10 days after
      tumour implantation. The extent of PDT-induced tumour necrosis was compared to
      the non-necrosed area and expressed in percentage. A locally invasive growing MPM
      tumour (3.1 +/- 1 mm diameter) without spontaneous necrosis diameter was found in
      all animals. For both sensitizers, focal intracavitary PDT was well tolerated at
      drug-light conditions recommended for clinical applications. Mediastinal organs
      were spared for both sensitizers but verteporfin resulted in a higher extent of
      tumour necrosis (80%) than mTHPC (50%). Drug dose escalation revealed a higher
      extent of PDT-related tumour necrosis for both sensitizers (mTHPC 55%,
      verteporfin 88%), however, verteporfin-PDT was associated with a higher toxicity
      than mTHPC-PDT.

PMID- 16785734
TI  - Implantation of the human embryo: research lines and models. From the
      implantation research network 'Fruitful'.
AB  - Infertility is an increasing problem all over the world, and it has been
      estimated that 10-15% of couples in fertile age have fertility problems. Likewise
      induced unsafe abortion is a serious threat to women's health. Despite advances
      made in assisted reproduction techniques, little progress has been made in
      increasing the success rate during fertility treatment. This document describes a
      wide range of projects carried out to increase the understanding in the field of
      embryo implantation research. The 'Fruitful' research network was created to
      encourage collaborations within the consortium and to describe our different
      research potentials to granting agencies or private sponsors.

PMID- 16785735
TI  - Metastatic mantle cell lymphoma presenting as a vaginal mass. A case report.
AB  - BACKGROUND: Vaginal masses are an uncommon finding in well-woman gynecologic
      examinations. The differential diagnosis includes cysts, leiomyomata, ectopic
      ureteroceles, infected granuloma, and malignancy. CASE: A 74-year-old woman with
      a history of mantle cell lymphoma was referred for vaginal prolapse. Examination
      revealed a vaginal mass, with MRI confirming 3 masses. Fine needle aspiration
      confirmed metastatic mantle cell lymphoma which later regressed with radiation
      therapy. CONCLUSION: Although vaginal masses are often rare and incidental
      findings during routine gynecologic examinations, a comprehensive differential
      diagnosis is required to avoid delays in treatment. Fine needle aspiration should
      be included as part of the arsenal of diagnostic tools because of its low cost
      and the ease with which it can be performed in a clinical setting.

PMID- 16785736
TI  - Hypertension and left ventricular hypertrophy in pediatric peritoneal dialysis
      patients: ambulatory blood pressure monitoring and echocardiographic evaluation.
AB  - BACKGROUND: Hypertension is a frequent complication of end-stage renal disease
      and left ventricular hypertrophy (LVH) is common in patients with poorly
      controlled hypertension. The aim of this study was to evaluate hypertension in
      pediatric peritoneal dialysis (PD) patients, to compare casual and ambulatory
      blood pressure (BP) measurements and to evaluate the impact of BP parameters on
      LVH. METHODS: The study comprised 25 PD patients (9 M, 16 F; mean age 14.14 +/-
      3.32 years) that have been followed in outpatient clinics. Medical records were
      reviewed for demographic features; casual BP measurements, ambulatory blood
      pressure monitoring (ABPM) and echocardiographic evaluation were applied to all
      patients. RESULTS: The mean 24-hour and daytime systolic blood pressure (SBP)
      values were found to be higher than casual SBP (p < 0.001). Significant
      difference was present in the frequency of hypertension between casual SBP (32%)
      and the mean daytime SBP (56%) (p < 0.05). Nighttime systolic hypertension was
      detected in 14 (56%) and diastolic hypertension in 16 (64%) patients. Elevated
      daytime SBP load and DBP load were detected in 64 and 76% of the patients,
      respectively. Elevated nighttime SBP load and DBP load were detected in 72% of
      the patients. Seventeen (68%) patients had attenuated dipping for SBP. The mean
      left ventricular mass index (LVMI) was 52.65 +/- 18.17 g/m(2.7) and 13 (52%)
      patients had LVH. LVMI was significantly correlated with casual BP measurements
      and the majority of ABPM parameters. CONCLUSION: The majority of pediatric PD
      patients had BP abnormalities in which severity was most accurately assessed with
      ABPM. Casual BP and majority of ABPM parameters were found to be significantly
      correlated with LVMI. Ambulatory blood pressure monitoring should be performed in
      all pediatric PD patients.

PMID- 16785737
TI  - Anaemia after renal transplantation--role of immunosuppressive drugs and a
      pathophysiological appraisal.
AB  - Improvements in patient care and longevity on dialysis programmes together with
      the increased numbers of patients referred for renal replacement therapy will
      inevitably result in enlarging numbers of subjects with functioning renal
      transplants. While this translates to a boon for the patients in terms of
      survival and quality of life, a very real problem has begun to emerge, that of
      post-transplantation anaemia (PTA). The prevalence of this condition has been
      estimated by several studies as varying somewhere between one third and two
      thirds of all patients, with the same attendant problems as anaemia in the
      context of chronic kidney disease. PTA is multifactorial in origin and involves
      interplay between a number of risk factors, not least of all the
      immunosuppressive protocol. It is the purpose of this article to briefly review
      the contribution from transplant immunosuppression to PTA and to assess its
      likely effects on and treatment options for patients.

PMID- 16785738
TI  - Immunosuppressive treatment of idiopathic focal segmental glomerulosclerosis: a
      five-year follow-up study.
AB  - BACKGROUND/AIMS: Focal segmental glomerulosclerosis (FSGS) is a common type of
      glomerular disease that can lead to chronic renal failure. Various therapeutic
      regimens have been used in nephrotic FSGS patients. The effect of treatment with
      prednisolone alone or its combination with azathioprine and cyclosporin and
      parameters related to a poor outcome are studied. METHODS: Fifty-one patients
      with idiopathic FSGS and a follow-up period of 5 years were included. Twenty-five
      were treated with prednisolone alone (1 mg/kg BW/day) or combination of
      prednisolone (0.5 mg/kg BW/day) with azathioprine (2 mg/kg BW/day) or
      cyclosporine (3 mg/kg BW/day) in gradually reduced doses whereas 26 patients
      received no immunosuppressive drugs. Lower prednisolone dose regimens were used
      as initial treatment in obese, borderline diabetics or patients with bone
      disease. The clinical course was estimated using the end-points of 50% or
      doubling of baseline serum creatinine and/or end-stage renal failure. The
      contribution of clinical and histological parameters in the clinical outcome was
      estimated by univariate and multivariate analyses. RESULTS: Increase of baseline
      serum creatinine by 50% during the follow-up period was observed in 2 treated and
      9 untreated patients (8% vs. 35%, p = 0.03) whereas doubling of serum creatinine
      in 2 and 5 patients respectively (8% vs. 19%, p = NS). End-stage renal failure
      developed in 4 of 51 patients (8%), 2 treated and 2 untreated (p = NS).
      Parameters related to a poor outcome were baseline serum creatinine and severity
      of glomerulosclerosis (multivariate analysis OR = 1.08, p = 0.01). Most of
      patients (68%) who reached end-points had persistent nephrotic syndrome during
      the follow-up. Remission of nephrotic syndrome was observed more frequently among
      treated (75 vs. 30.7%, p = 0.05). Prednisolone alone was followed by remission of
      nephrotic syndrome in 62.5% whereas combination of lower prednisolone dose with
      azathioprine and cyclosporin in 80 and 85.7% of patients. No serious side-effects
      were observed. CONCLUSION: This and previous studies suggest that steroid and/or
      immunosuppressive therapy have a role in amelioration of the clinical course and
      remission of nephrotic syndrome in patients with FSGS A combination of low
      predisolone dose with cyclosporine could be used as initial treatment in patients
      with higher risk for side-effects from the usual prednisolone dose.

PMID- 16785739
TI  - Focal segmental glomerulosclerosis--does treatment work?

PMID- 16785740
TI  - The relationship of microalbuminuria with metabolic syndrome.
AB  - BACKGROUND/AIMS: Microalbuminuria and the metabolic syndrome are risk factors for
      cardiovascular disease. The aim of this study is to examine the prevalence of
      microalbuminuira and to document the relationship of microalbuminuria with the
      metabolic syndrome in a large population of Korean subjects. METHODS: We examined
      the cross-sectional association of microalbuminuria with the components of the
      metabolic syndrome and with other cardiovascular risk factors in 6,588 Korean
      adults who took part in a health examination program. RESULTS: The prevalence of
      microalbuminuria was 4.2% in the non-metabolic syndrome group (n = 5,902), and
      14.4% in the metabolic syndrome group (n = 686). The odds ratio of
      microalbuminuria in the adults with the metabolic syndrome compared with those
      adults without the metabolic syndrome was 1.53 (1.13-2.07 95% CI). In the
      multiple logistic regression analysis, as compared with the subjects without an
      elevated blood pressure, a low high-density lipoprotein cholesterol level, a high
      triglyceride level, a high plasma glucose level and a large waist circumference,
      the odds ratios for microalbuminuria with these components, after adjustment was
      made for the body mass index, the high-sensitivity C-reactive protein level and
      the homeostasis model assessment, were 2.17 (95% CI 1.71-2.76), 2.84 (95% CI 1.55
      5.21), 1.30 (95% CI 1.03-1.65) and 2.68 (95% CI 2.04-3.51), respectively. The
      corresponding multivariate-adjusted odds ratios of microalbuminuria for the
      participants with 1, 2, 3, and 4 and 5 components of metabolic syndrome were 1.79
      (95% CI 1.24-2.59), 2.35 (95% CI 1.58-3.51), 3.23 (95% CI 2.07-5.25), and 4.22
      (95% CI 2.13-8.35), respectively. CONCLUSION: There was a significantly graded
      relationship between the number of metabolic syndrome components and the
      corresponding prevalence of microalbuminuria. These findings suggest
      microalbuminuria is strongly related with the components of the metabolic
      syndrome.

PMID- 16785741
TI  - Multislice computed tomographic angiography in evaluating dysfunction of the
      vascular access in hemodialysis patients.
AB  - AIMS: To introduce our preliminary experience in using multislice computed
      tomographic (CT) angiography (MSCTA) to assess stenoses of the hemodialysis
      vascular access and to guide revising operation or percutaneous transluminal
      angioplasty (PTA). METHODS: Contrast-enhanced 16-slice spiral CT was used to
      examine 22 hemodialysis patients with various dysfunctions of their vascular
      access. The transverse source images were reformatted as maximum intensity
      projection, volume-rendering, and multiple/curved planar reconstruction images.
      RESULTS: The whole spectrum of arteriovenous fistulas (AVF) with the feeding
      artery, anastomoses, and outflow tract up to the superior caval vein was clearly
      displayed in all patients. According to the results of MSCTA, AVF-revising
      surgery was done in 11 patients, and PTA under the guide of digital subtraction
      angiography (DSA) was done in 5 patients. The results of MSCTA coincide with the
      findings of surgery or DSA in these 16 patients. CONCLUSIONS: In our opinion,
      MSCTA is a good noninvasive diagnostic technique to detect various hemodialysis
      vascular access abnormalities. It is more economical than DSA in the present
      medical settings and could replace DSA in the imaging of hemodialysis vascular
      access and provide important information for further AVF-revising surgery or PTA.

PMID- 16785742
TI  - Recent insights into experimental mouse models of diabetic nephropathy.
AB  - BACKGROUND/AIMS: Mouse models are an essential experimental tool for
      investigating the role of molecular mechanisms and genetic susceptibility in the
      development of diabetic nephropathy. METHODS: The most widely used inbred strain,
      the C57BL/6 mouse, is commonly used in streptozotocin-induced models of type 1
      diabetes and is particularly susceptible to obesity-induced type 2 diabetes.
      However, use of this strain has been criticised by studies suggesting that it is
      relatively resistant to renal injury. RESULTS: Recent refinement of these models
      and utilisation of genetically modified (knockout and transgenic) mice on a
      C57BL/6 background has provided important insights into the roles of oxidative
      stress, advanced glycation end products, inflammation and profibrotic mechanisms
      in the development of type 1 and type 2 diabetic nephropathy. CONCLUSION: These
      findings demonstrate the utility of mouse models for identifying and testing
      novel therapeutic strategies which could translate into better protection against
      the human disease.

PMID- 16785743
TI  - Leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4, Gpr48) is
      essential for renal development in mice.
AB  - Leucine-rich repeat-containing G protein-coupled receptor (LGR)-4 is a G protein
      coupled receptor (GPCR) with a seven-transmembrane domain structure. LGRs are
      evolutionally and structurally phylogenetic, classified into three subgroups and
      are members of the so-called orphan receptors whose ligands have yet to be
      identified. We generated knockout mice lacking Lgr4(Gpr48) by targeted deletion
      of part of exon 18, which codes for the transmembrane and signal-transducing
      domains of the receptor. Lgr4 null mice were born at much less than the 25%
      expected frequency from crosses of Lgr4 heterozygous mice (Lgr4+/-). Lgr4 null
      mice that survived in utero died shortly after birth in almost all cases. We
      observed striking renal hypoplasia in the null mice, accompanied by elevated
      concentration of plasma creatinine. Histological analysis of the P0 null mouse
      kidney showed a notable decrease in the total number and density of the
      glomerulus. Thus, the function of Lgr4 is essential to regulate renal development
      in the mouse. This study suggests that the Lgr4 gene is a new and important
      member of LGRs involved in a group of genes responsible for hereditary disease in
      the kidney.

PMID- 16785744
TI  - Increased TGF-alpha and EGF Receptor mRNA expression in response to neonatal
      unilateral partial ureter obstruction in rats.
AB  - AIM: To evaluate the potential role of members of the epidermal growth factor
      (EGF) family in altered renal growth caused by partial ureteral obstruction in
      the developing obstructed and non-obstructed kidneys. METHODS: During anesthesia
      either the upper fourth (n = 6-7) or the upper two-thirds of the left ureter (n =
      6-7) were embedded into the psoas muscle in newborn rats resulting in mild or
      severe partial unilateral obstruction, respectively, which was maintained during
      the following 24 weeks. Sham-operated control rats were prepared in parallel (n =
      6-7). Real time PCR assays were used to quantify mRNA encoding EGF, TGF-alpha, HB
      EGF and EGF receptor. The expression of ribosomal RNA was determined to relate
      the specific mRNA expression of members of the EGF system. RESULTS: Relative
      expression of TGF-alpha and EGF receptor mRNA levels were elevated significantly
      both in the severe and mild obstructed kidney compared with the contralateral or
      sham-operated kidneys after 24 weeks of obstruction. However, the expression of
      neither EGF nor HB-EGF was changed after obstruction. CONCLUSION: The increased
      expression of TGF-alpha and its receptor in the obstructed kidney might be
      related to a cell-survival function in the affected cells possibly by protecting
      them from entering apoptosis.

PMID- 16785745
TI  - Central thyrotropin-releasing hormone infusion opposes cardiovascular and
      metabolic suppression during caloric restriction.
AB  - Inhibition of hypothalamic thyrotropin-releasing hormone (TRH) neuronal activity
      is a well-established adaptation to caloric restriction (CR) that suppresses
      pituitary secretion of thyroid-stimulating hormone, but may also participate in
      modulation of autonomic function. Thus, we hypothesized that decreased
      hypothalamic TRH activity contributes to CR-induced bradycardia and decreased
      metabolic rate. To test this hypothesis, male Sprague-Dawley rats were
      instrumented with telemetry devices for measurement of heart rate (HR) and blood
      pressure (BP) and a lateral intracerebroventricular (i.c.v.) guide cannula for
      central infusions. After recovery, rats were housed in metabolic chambers and
      given either ad libitum(ad-lib) or CR treatments for 7 days; half of each diet
      group was then given continuous i.c.v. infusions of TRH (25 nmol/h) or saline
      (0.25 microl/h) for 7 days via osmotic pump. This dose of TRH did not
      significantly alter peripheral free T(4) levels. In ad-lib rats, TRH infusion
      produced small reductions in food intake and small increases in HR and BP over
      saline-infused controls. In CR rats, TRH infusion resulted in an increase in HR
      and also energy expenditure over saline-infused controls. These results support
      the hypothesis that suppression of central TRH activity contributes to the
      homeostatic suppression of energy expenditure and HR observed during CR.

PMID- 16785746
TI  - Signaling pathway involved in the pro-apoptotic effect of dopamine in the GH3
      pituitary cell line.
AB  - Besides its physiological role as a neurotransmitter, dopamine (DA) induces
      apoptosis in the central nervous system. This effect is mediated partly by the DA
      transporter (DAT) and involves reactive oxygen species (ROS) formation as well as
      oxidative stress. In the pituitary, the inhibitory control by DA of prolactin
      release and synthesis and lactotrope cell proliferation is well known, while the
      pro-apoptotic effect of DA remains unclear. Our aim was to study the pro
      apoptotic effect of DA in the GH3 mammosomatotrope cell line and determine the DA
      mechanism that leads to apoptosis in these cells. Using flow cytometry, Western
      blot, and confocal microscopy, we showed for the first time that DA induced: (1)
      loss of mitochondrial potential; (2) relocation of Bax to the mitochondria; (3)
      cytochrome c release; (4) caspase-3 activation, and (5) nuclear fragmentation,
      resulting in apoptosis. We observed that DAT was expressed in GH3 cells and
      participated in the DA effect, as apoptosis was significantly reversed in the
      presence of DAT inhibitors. Direct measurement showed that DA rapidly increased
      the formation of intracellular ROS. The antioxidant N-acetyl-L-cysteine (NAC)
      effectively blocked DA-induced ROS formation and apoptosis. Neither JNK nor p38
      were involved in this process, so we suggest that the mitochondrial pore of
      transition is the likely target of the ROS generated by DA. These data provide
      the first evidence that DA triggers apoptosis in pituitary cells via a mechanism
      involving DAT and oxidative stress. These findings may be particularly relevant
      in understanding lactotrope apoptosis during postnatal life.

PMID- 16785747
TI  - Bartter syndromes and other salt-losing tubulopathies.
AB  - Genetic studies into rare inborn errors of renal tubular sodium handling in man
      have brought many interesting, sometimes surprising insights into how we can
      maintain our bodies' electrolytes and fluids homeostasis. The cloning and
      identification of sodium transporting genes and proteins like NHE3, NKCC2, ROMK,
      CLCNKB, NCC, and EnaC has considerably improved our understanding of renal salt
      handling. Subsequently, studies of genetically engineered animals provided even
      more insight into the complex renal physiology. The recent discovery of the WNK
      kinases as regulators and integrators of specific renal transport pathways helped
      elucidate this further and lets us start to appreciate the full complexity of
      renal sodium handling. We summarize recent findings in the field in the context
      of human diseases and a pathophysiologic basis for their treatment.

PMID- 16785748
TI  - Analbuminemic Nagase rats: blood pressure response to dietary salt challenge.
AB  - BACKGROUND: The role of albumin on blood pressure response to different salt
      challenges is not known. Therefore, we studied the blood pressure response of
      analbuminemic Nagase rats (NAR) to different salt challenges. 11beta
      Hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the enzyme regulating the
      glucocorticoid access to the mineralocorticoid receptor, an enzyme that is
      decreased in humans with salt sensitive hypertension and other diseases with
      abnormal renal salt retention, was assessed during salt challenges. METHODS:
      Blood pressure was measured continuously by an intra-arterial catheter and a
      telemetry system in NAR (n = 8). NAR were set successively for 7 days on a normal
      (0.45% NaCl), high (8% NaCl), low (0.1% NaCl) and normal salt diet again, to
      assess salt related response in mean systolic (SBP) and diastolic blood pressure
      (DBP). 11beta-HSD2activity was assessed by measuring the urinary (THB + 5alpha
      THB)/THA ratio with gas chromatography - mass spectrometry. RESULTS: Mean SBP and
      DBP increased with high salt intake (normal salt vs. high salt: SBP: 114 +/- 1
      vs.119 +/- 3 mm Hg, p < 0.01; DBP: 84 +/- 1 vs. 88 +/- 3 mm Hg; n = 8; p < 0.01).
      Urinary (THB +5alpha-THB)/THA ratio increased during the high-salt period when
      compared to the normal-salt period (high salt vs. normal salt: 0.52 +/- 0.10 vs.
      0.37 +/- 0.07; p = 0.05) indicating decreased 11beta-HSD2activity. CONCLUSION:
      Analbuminemic Nagase rats express increased blood pressure and reduced 11beta
      HSD2 activity in response to a high-salt diet.

PMID- 16785749
TI  - Localization of NBC1 variants in rat kidney.
AB  - Na+-HCO3- cotransporter (NBC1) plays a major role in bicarbonate reabsorption
      from proximal tubules. In a previous immunohistochemical study on human kidney,
      we showed that the kidney-type transporter (kNBC1) was abundantly expressed in
      the basolateral membranes of proximal tubules while the expression of pancreatic
      type transporter (pNBC1) was undetectable. In the present study we tried to
      determine the localization of NBC1 variants in rat kidney using the antibodies
      against the unique N-terminal regions of kNBC1 and pNBC1. In Western blot
      analysis on the membrane-enriched fraction from rat kidney both anti-kNBC1 and
      anti-pNBC1 antibodies yielded a approximately 130 kDa band. In
      immunohistochemical analysis with confocal microscopy the anti-kNBC1 antibody
      produced a strong and exclusively basolateral labeling in proximal tubules. On
      the other hand, the occasional pNBC1 labeling was detected in the apical
      membranes of proximal tubules. The electron microscopic observation further
      supported the basolateral localization of kNBC1 as well as the localization of
      pNBC1 on the basis of the brush border. Acute metabolic acidosis did not change
      the protein expression levels as well as the intracellular distribution of both
      NBC1 variants in rat kidney. These results are consistent with a view that kNBC1
      is the dominant variant that mediates bicarbonate reabsorption from rat renal
      proximal tubules. They also indicate that species difference may exist regarding
      the distribution of NBC1 variants in kidney.

PMID- 16785750
TI  - Experimental model for proliferative vitreoretinopathy by intravitreal dispase:
      limited by zonulolysis and cataract.
AB  - BACKGROUND: The intravitreal injection of dispase has been shown to be a valuable
      method for induction of experimental PVR. The goal of the present study was to
      gain additional information about potential side effects associated with this
      method. METHODS: Twenty-one pigmented rabbits received a single injection of
      dispase under topical anesthesia to one eye only, contralateral eyes served as
      untreated control. The animals were injected with doses from 0.045 to 0.065 units
      of dispase: 8 animals received 0.045 units, 9 animals 0.055 units and 4 animals
      0.065 units. RESULTS: Proliferative vitreoretinopathy occurred in 81% of the
      treated eyes. In 90% cataract formation was observed. Lens luxation was present
      in 47.3% of the cataract eyes. CONCLUSION: Intravitreal injection of dispase
      resulted in the reproducible induction of PVR in addition to cataract formation
      and lens luxation. Whether these effects may all be associated with a toxic
      reaction or whether the proliferative changes are solely triggered by endogenous
      reactions similar to the pathomechanism of human PVR and whether the cataract
      formation and the lens luxation may be avoided by changing the method of
      injection require further investigation.

PMID- 16785751
TI  - Pentoxifylline decreases up-regulated nuclear factor kappa B activation and
      cytokine production in the rat retina following transient ischemia.
AB  - AIM: To investigate whether pentoxifylline (PTX) could influence the increased
      cytokine gene expression in the retina flowing transient ischemia, and if so,
      whether it acts through the modulation of nuclear factor kappa B (NF-kappaB)
      activation. METHODS: Sprague-Dawley rats were randomly divided into three equal
      groups: control group, saline-treated group, and PTX-treated group. Increased
      intraocular pressure was applied for 90 min to induce retinal ischemia, and
      reperfusion was established by lowering the bottle to eye level. The reperfusion
      period lasted for 48 h. In the PTX-treated group, an initial dose of 20 mg PTX
      was injected via tail vein at the beginning of reperfusion. Then the rat received
      infusion of PTX at a rate of 6 mg/kg/h throughout the entire reperfusion period.
      The retinal tissues were collected at the end of 1, 6, 12, 24, and 48 h of
      reperfusion, respectively, for biochemical analysis. Histological examination was
      done on the tissues collected at the end of 48 h after reperfusion. RESULTS:
      Histological examination revealed reduction of overall retinal thickness and
      thinning of the inner retinal layer in saline-treated rats after 48-hour
      reperfusion. However, PTX treatment significantly reduced the loss of overall
      retinal thickness and thinning of inner retinal layers. Dramatic increase in NF
      kappaB activation, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta
      (IL-1beta) production and mRNA expression were observed in the saline-treated
      group after reperfusion, with the peak reached around 12 h. In the PTX-treated
      group, NF-kappaB activation, TNF-alpha and IL-1beta production and mRNA
      expression were significantly reduced at each corresponding time point compared
      to the saline-treated group. CONCLUSION: PTX decreased the up-regulated
      activation of NF-kappaB and the expression of proinflammatory cytokines, TNF
      alpha and IL-1beta in rat retinas following ischemia/reperfusion. This may
      contribute to significantly reduce the loss of overall retinal thickness and
      thinning of inner retinal layers.

PMID- 16785752
TI  - Alkali burns of the eye: effect of immediate copious irrigation with tap water on
      their severity.
AB  - PURPOSE: To examine the effect of immediate irrigation on ocular alkali burn.
      METHODS: Information on the injury, immediate irrigation, and ocular findings was
      retrospectively obtained from each patient's record. RESULTS: 36 patients (49
      eyes) irrigated their eyes with tap water (the irrigation group) and 17 patients
      (29 eyes) did not (no irrigation group). The mean age of patients in the
      irrigation and no irrigation groups was 30 and 53 years, respectively. According
      to Hugher's classification, 76% of eyes in the irrigation group had grade 1
      injury, while 86% of eyes in the no irrigation group had grade 2 injuries. Mean
      time from the injury until healing was 8 days in the irrigation group and 29 days
      in the no irrigation group, respectively. CONCLUSION: Immediate copious
      irrigation with tap water reduced the severity in alkali burns of the eye and
      shortened the healing time.

PMID- 16785753
TI  - The differential diagnosis of red eye: a survey of medical practitioners from
      Eastern Europe and the Middle East.
AB  - A survey amongst ophthalmologists and general medical practitioners from nine
      countries in Eastern Europe and the Middle East was conducted to estimate the
      percentage of patients presenting with a red eye and to examine differential
      diagnosis and treatment. Practitioners recorded brief details of every patient
      seen and detailed information concerning signs and symptoms, differential
      diagnosis and treatment for all patients presenting with a red eye during 20
      consecutive days in the period between May and September 2004. Red eyes accounted
      for approximately 15% of consultations with ophthalmologists and almost 6% with
      general medical practitioners. Allergic conjunctivitis was the most common
      diagnosis (35%), followed by dry eye (25%) and bacterial conjunctivitis (24%).
      General medical practitioners were far more likely to prescribe a combination
      topical antibiotic and steroid preparation than ophthalmologists. This survey
      illustrates that red eye remains a very important problem for both
      ophthalmologists and general medical practitioners. Identification of dry eye as
      a common cause of red eye symptoms and more appropriate treatment of dry eye,
      allergic conjunctivitis and viral conjunctivitis are key messages to emerge.

PMID- 16785754
TI  - Acanthamoeba keratitis and contact lens disinfecting solutions.
AB  - OBJECTIVES: To report cases of culture-proved Acanthamoeba keratitis in Greece
      over a 10-year period and to evaluate the effectiveness of the commonly used
      commercial contact lens disinfecting systems in clinical cases of Acanthamoeba
      keratitis. MATERIAL AND METHODS: During the years 1994-2004, 45 contact lens
      wearers and 3 non-contact lens wearers presenting with symptoms and signs of
      keratitis underwent corneal sampling. The scrapings obtained were inoculated
      directly onto appropriate culture media for bacteria, fungi and Acanthamoeba. All
      proved positive for Acanthamoeba. The contact lenses and contact lens
      disinfecting solutions (16 one-step 3% hydrogen peroxide and 3 multipurpose
      solutions) of 19/45 patients with culture-proven Acanthamoeba keratitis were
      cultured for bacteria, fungi and Acanthamoeba. RESULTS: Acanthamoeba was isolated
      from contact lenses and contact lens disinfecting solutions in all 19 cases of
      Acanthamoeba keratitis studied. CONCLUSIONS: The main risk factor for corneal
      infection in contact lens wearers is the use of contact lens disinfecting systems
      ineffective at killing Acanthamoeba cysts and trophozoites, as well as bacteria
      and fungi. Improvement or development of new contact lens disinfecting systems by
      manufacturers is needed to prevent Acanthamoeba keratitis.

PMID- 16785755
TI  - The effects of droperidol in perforating keratoplasty.
AB  - PURPOSE: To evaluate the intraoperative and postoperative effects of droperidol
      administered with general anesthesia during perforating keratoplasty. METHODS: A
      prospective, randomized, double-masked clinical trial. Twenty-seven patients
      undergoing penetrating keratoplasty under general anesthesia were included.
      Patients were assigned randomly to two groups. Fifteen subjects received
      droperidol during induction of general anesthesia. Twelve control patients
      received general anesthesia without droperidol. RESULTS: Droperidol significantly
      reduced fellow eye intraocular pressure (p < 0.0001). Intraoperative anterior
      chamber depth was significantly deeper with droperidol (p = 0.0002). Iris bulging
      was observed in 25% of the control group and 0% with droperidol. There was
      significantly less postoperative nausea in the droperidol group (p = 0.038).
      There was less postoperative vomiting in the droperidol group, although the
      difference was not significant (p = 0.07). Postoperative wound gaping was
      observed in 2 patients; both of them did not receive droperidol. CONCLUSIONS:
      Droperidol effectively reduces intraoperative and postoperative complications in
      keratoplasty surgery.

PMID- 16785756
TI  - Different plasma levels of vascular endothelial growth factor and nitric oxide
      between patients with choroidal and retinal neovascularization.
AB  - Because the blood flow is much more intense in the choroid than in the retina, it
      is interesting to explore whether choroidal neovascularization (CNV) is more
      influenced by plasma angiogenic factors than retinal neovascularization. The aim
      of this study was to investigate plasma profiles of vascular endothelial growth
      factor (VEGF) and nitric oxide (NO) in patients with CNV due to age-related
      macular degeneration (AMD) and in those with retinal neovascularization due to
      proliferative diabetic retinopathy (PDR). Seventy-seven subjects with AMD, 22
      with PDR, and 42 nondiabetic, non-AMD controls were enrolled in this comparative
      case series. AMD subjects were classified into three groups: dry type (dry AMD, n
      = 17), wet type with active CNV (CNV/AMD, n = 42), and disciform scar due to
      advanced wet AMD (scar/AMD, n = 18). Plasma VEGF and NO levels of each subject
      were measured with enzyme-linked immunosorbent assay and chemiluminescence,
      respectively. Plasma VEGF level in CNV/AMD (median 256.0 pg/ml, interquartile
      range 146.4-375.3 pg/ml) was significantly higher than in PDR (124.8 pg/ml, 75.7
      215.3 pg/ml; p = 0.004) and controls (120.3 pg/ml, 82.8-168.2 pg/ml, p =0.001).
      CNV/AMD also had the highest VEGF level among the AMD subgroups. Plasma NO level
      was significantly elevated in PDR (137.4 microM, 63.7-240.1 microM) when compared
      with CNV/AMD (71.8 microM, 42.4-113.3 microM; p = 0.004) and controls (62.6
      microM, 39.0-114.9 microM; p = 0.002). There was no significant difference in NO
      levels among the AMD subgroups. No significant correlation between VEGF and NO
      levels was noted. These findings indicate that both circulating VEGF and NO may
      play different roles in the pathogenesis of retinal neovascularization and CNV.

PMID- 16785757
TI  - A community-based epidemiologic study of gender differences in the relationship
      between insulin resistance/beta-cell dysfunction and diabetic retinopathy among
      type 2 diabetic patients in Kinmen, Taiwan.
AB  - PURPOSE: The purpose of this study was to explore whether there were gender
      differences in the relation of insulin resistance and beta-cell dysfunction to
      diabetic retinopathy among type 2 diabetic patients. METHODS: From 1999 to 2002,
      a screening regimen for diabetic retinopathy was performed by a panel of
      ophthalmologists using ophthalmoscopy and 45-degree color fundus photography to
      examine the fundus in a total of 971 type 2 diabetic patients examined between
      1991 and 1993 in Kinmen, Taiwan. Seven hundred and twenty-five type 2 diabetic
      patients (301 males and 424 females) attended ophthalmological fundus checkup.
      RESULTS: The response rate in males and females was 71.3 and 77.2%. The
      proportion of diabetic retinopathy at the first eye screening was 16.3% in males
      and 20.1% in females. From the multiple logistic regression, the type of diabetes
      (known cases vs. new cases) was a significant factor of diabetic retinopathy in
      both males (OR = 3.65, 95% CI: 1.59-8.37) and females (OR = 3.66, 95% CI: 2.01
      6.70). Diabetic retinopathy was also strongly affected by the homeostasis model
      assessment of insulin resistance (HOMA IR) and homeostasis model assessment of
      beta-cell dysfunction (HOMA beta-cell) (p < 0.0001 for trend test). In males,
      those who were in the 2nd quartile, 3rd quartile, and 4th quartile of HOMA IR had
      4.87 times (95% CI: 1.18-20.11), 6.83 times (95% CI: 1.91-24.46), and 10.15 times
      (95% CI: 2.42-42.56) the risk for diabetic retinopathy as compared to those in
      the 1st quartile. There was a reduced risk for diabetic retinopathy in relation
      to HOMA beta-cell for the 2nd quartile, 3rd quartile, and 4th quartile of 86%
      (95% CI: 37-97%), 95% (95% CI: 77-99%), and 96% (95% CI: 78-99%) as compared to
      that in the 1st quartile. Only the 4th quartile had a significant risk (OR =
      2.62, 95% CI: 1.17-5.86) for diabetic retinopathy as compared to that in the 1st
      quartile in females. The reduced risk for diabetic retinopathy found in relation
      to HOMA beta-cell for the 3rd and 4th quartiles were 66% (95% CI: 6-88%) and 66%
      (95% CI: 10-87%) as compared to that in the 1st quartile. CONCLUSIONS: Gender
      differences in the relationship between insulin resistance/beta-cell dysfunction
      and diabetic retinopathy were demonstrated in type 2 diabetic patients.

PMID- 16785758
TI  - Problems associated with the 25-gauge transconjunctival sutureless vitrectomy
      system during and after surgery.
AB  - OBJECTIVE: To report the initial experiences with the 25-gauge transconjunctival
      sutureless vitrectomy (TSV) system, including intraoperative and postoperative
      problems. METHODS: We retrospectively reviewed the medical records and surgical
      videotapes of 50 consecutive patients who underwent vitrectomy performed by one
      surgeon using the TSV system. RESULTS: Intraoperatively, we encountered such
      problems as difficulty in inserting the microcannula, which led to deformity,
      instability of the microcannula, self-disconnection of the infusion tip and
      resultant lens damage, and conversion to 20-gauge conventional vitrectomy.
      Postoperatively, there were 8 cases with hypotony (IOP < 6 mm Hg) on day 1, 6
      cases with elevated IOP, and 3 cases with retinal detachment during follow-up.
      CONCLUSION: Though certain problems exist during and after surgeries using TSV,
      this system is both convenient and safe for various vitreoretinal procedures.

PMID- 16785759
TI  - Intersession reproducibility of retinal nerve fiber layer thickness measurements
      by GDx-VCC in healthy and glaucomatous eyes.
AB  - BACKGROUND: To assess intersession reproducibility of retinal nerve fiber layer
      (RNFL) thickness measurements on scanning laser polarimetry with variable corneal
      compensation (GDx-VCC) in a sample of healthy subjects and glaucoma patients.
      METHODS: One eye each from 29 healthy and 29 glaucomatous subjects was selected
      and underwent RNFL scanning by the same operator at baseline and 1 week later.
      Glaucoma diagnosis relied on the presence of a reproducible defect on automated
      perimetry. GDx-VCC parameters considered were those available on page 1 of the
      printout [TSNIT average and standard deviation (SD), superior and inferior
      average (SA, IA), Nerve Fiber Indicator]. Reproducibility was assessed by
      calculating coefficient of variation and intraclass correlation coefficient
      separately for the two groups and for each parameter. The percentage of eyes with
      an intersession difference in thickness parameters of more than 5% was also
      calculated. RESULTS: Coefficient of variation was <6% for TSNIT average, SA and
      IA in both groups. Corresponding values for TSNIT SD in healthy subjects and in
      glaucoma patients were 13.7 and 11.4%, respectively, whereas for Nerve Fiber
      Indicator they were 82.9 and 13.3%. Intraclass correlation coefficient ranged
      from 0.794 to 0.907 in healthy subjects and from 0.924 to 0.972 in glaucoma
      patients. In healthy subjects, TSNIT average, SA and IA intersession difference
      was 5% or less in 55-69% of eyes, whereas the value for TSNIT SD was 34.5%.
      Corresponding values in glaucomatous eyes ranged from 69 to 79.3% for TSNIT
      average, SA and IA and was 37.9% for TSNIT SD. CONCLUSIONS: Intersession
      reproducibility of RNFL thickness measurements on GDx-VCC is high, both in
      healthy and in glaucomatous eyes. In a few cases, however, intersession variation
      may be larger than 10%. Caution is necessary while interpreting these changes
      during follow-up, in order to separate physiological variability from real RNFL
      thickness variations.

PMID- 16785760
TI  - Regression-related factors before and after laser in situ keratomileusis.
AB  - The aim of this study was to evaluate the refractive regression-related factors
      before and after laser in situ keratomileusis (LASIK) for myopia and give a
      reasonable way to prevent it. The consecutive patients who underwent LASIK from
      January to June 2004 were reviewed retrospectively. Thirteen eyes from 8 patients
      with myopic regression and 60 eyes from 42 patients with no myopic regression
      within 12 months of follow-up were enrolled. We compared the pre- and
      postoperative data which were associated with regression in the two groups. The
      mean preoperative intraocular pressure (IOP) was significantly higher in the
      regression group than in the non-regression group (p = 0.03). During the period
      of 12 months, the two groups differed in corneal bowing. In the regression group,
      both posterior and anterior corneal surfaces were significantly bowing (all p <
      0.05). In contrast, in the non-regression group, both posterior and anterior
      surfaces were relatively stable (all p > 0.05). The higher preoperative IOP and
      the progressive postoperative biomechanical bowing in the posterior and anterior
      surfaces of the cornea are two factors related to myopic regression in this
      study. Lowering the IOP preoperatively and postoperatively may be an effective
      way to prevent the myopic regression after LASIK.

PMID- 16785761
TI  - Mycobacterium abscessus keratitis after LASIK with IntraLase femtosecond laser.
AB  - A healthy 38-year-old woman developed 2 white spots in her left eye 2 weeks after
      bilateral laser in situ keratomileusis (LASIK) using the IntraLase femtosecond
      laser. Initial treatment included levofloxacin 0.5% but was unsuccessful. The
      surgeon irrigated the interface and repositioned the flap due to a worsened
      lesion. She was referred to us after the keratitis had not improved. The flap was
      lifted for collection of the specimen and irrigation of the interface. The
      keratitis was treated with intensive topical clarithromycin 1%, amikacin 1.25%
      and oral clarithromycin, which improved her clinical condition. She developed a
      toxic reaction to amikacin 1.25%, which was replaced by moxifloxacin 0.5%.
      Mycobacterium abscessus was identified. The keratitis resolved over 2 months.
      Five months after treatment, the patient had a visual acuity of 20/20 with
      correction. Nontuberculous mycobacteria should be considered as an etiologic
      agent, even in cases of infectious keratitis after LASIK using the femtosecond
      laser.

PMID- 16785762
TI  - Involvement of cAMP response element-binding protein activation in salivary
      secretion.
AB  - OBJECTIVE: Saliva secretion is mediated by cAMP and the calcium signaling pathway
      in salivary acinar cells. The PKA signaling pathway plays an important role in
      protein secretion through the activation of cAMP, in fluid secretion through the
      elevation of intracellular calcium and in the activation of cAMP response element
      binding protein (CREB), which is involved in these signaling cascades. In this
      study, we investigated whether the activation of CREB plays a part in the
      salivary secretion in mice. METHODS: We examined CREB activation by assessing
      phosphorylation at the serine-133 position using Western blotting. RESULTS:
      Carbachol (a muscarinic acetylcholine agonist) and isoproterenol (a beta
      adrenergic agonist) markedly activated CREB in parotid acinar cells. Carbachol
      and isoproterenol-induced CREB phosphorylation was blocked by atropine (a
      muscarinic acetylcholine antagonist) and propranolol (a beta-adrenergic
      antagonist), respectively. The PKA inhibitor H89 inhibited CREB activation, but
      the PLC inhibitor U73122 did not. Moreover, carbachol- and isoproterenol
      stimulated amylase secretion from parotid acinar cells was inhibited by H89 and
      adenoviral dominant-negative CREB. CONCLUSION: These results indicate that the
      muscarinic and beta-adrenergic activation of CREB was mediated through the PKA
      pathway and that CREB is involved in protein secretion from parotid acinar cells.

PMID- 16785763
TI  - Significance of Akt phosphorylation on tumor growth and vascular endothelial
      growth factor expression in human gastric carcinoma.
AB  - OBJECTIVE: Hypoxia is known to be a prevalent stress stimulus and increases the
      transcription of vascular endothelial growth factor (VEGF) mediated by hypoxia
      inducible factor-1alpha (HIF-1alpha). We investigated the role of phosphatidyl
      inositol-3 OH kinase (PI3K)-Akt signaling in the regulation of HIF-1alpha and
      VEGF expression in human gastric adenocarcinoma. METHODS: The growth-inhibitory
      and apoptosis-inducing effects of the LY294002 PI3K inhibitor were analyzed in
      four gastric cancer cell lines and in vivo. The regulatory mechanism of VEGF and
      HIF-1alpha expression under hypoxic conditions was examined in the cell cultures.
      In 88 gastric cancer tissue samples, phosphorylated Akt and VEGF expression were
      analyzed immunohistochemically. RESULTS: LY294002 suppressed cell proliferation
      but induced apoptosis with decreased levels of phosphorylated Akt. HIF-1alpha
      expression and VEGF secretion were induced under hypoxic conditions and VEGF
      protein secretion was significantly decreased by treatment with LY294002. In
      tumor samples, phosphorylated Akt expression was detected in 57% of the tumors,
      which was correlated with high VEGF expression, angiogenesis, clinicopathological
      parameters as well as a poor outcome. CONCLUSIONS: These findings suggest that
      phosphorylated Akt (Ser473) reflects the grade of malignancy in human gastric
      adenocarcinomas, not only in terms of tumor growth but also with respect to tumor
      angiogenesis.

PMID- 16785764
TI  - Improvements in the analysis strategy make single nucleotide polymorphism
      analysis a powerful tool in the detection and characterization of amplified
      chromosomal regions in human tumors.
AB  - OBJECTIVE: Single nucleotide polymorphism analysis (SNP) has recently been
      proposed as an alternative technique to comparative genomic hybridization (CGH)
      for defining loss of heterozygosity and gene copy number changes in a single
      experimental setup. In order to assess the potential of SNP analysis to
      complement or, ultimately, substitute CGH results, we applied both techniques to
      five primary tumor samples and two tumor cell lines. This was complemented by
      dilution experiments based on normal lymphocyte DNA to decipher the lower
      detection limit for genetic alterations. METHODS/RESULTS: Using an in-house
      software tool, we demonstrated that SNP analysis permits the generation of
      chromosomal alteration patterns that largely resemble conventional CGH ratio
      profiles of a given tumor/cell line. Moreover, compared to CGH, our SNP software
      tool allows a much more detailed definition of amplicon sizes and involved
      candidate genes. This advantage even persisted when the technique was applied to
      DNA with more than 60% of nontumor content. However, the detection of chromosomal
      losses is severely hampered by the presence of nontumor DNA so that the use of
      the SNP technique should be limited to tumor samples with more than 80% tumor
      DNA. CONCLUSION: SNP analysis is a very valuable tool for the detection and
      characterization of high-level chromosomal amplifications in the vast majority of
      primary tumor samples. Our software tool improves the analysis of SNP data and
      the presentation of the results, bridging the gap to existing CGH knowledge
      (http://bioinformatics.uni-muenster.de, 'Publications and Supplements').

PMID- 16785765
TI  - Impaired endotoxin tolerance induction in patients with familial Mediterranean
      fever.
AB  - OBJECTIVE: To investigate periodic disturbances in proinflammatory activation of
      neutrophils and monocytes in patients with familial Mediterranean fever (FMF)
      both during an attack and in remission. METHODS: 20 FMF patients, who were naive
      to colchicine treatment and did not have amyloidosis, and 10 patients with
      Behcet's disease (BD) were enrolled in this study. Phagocytosis, respiratory
      burst, CD11a/CD18 expression and intracellular cytokine synthesis were determined
      by flow cytometry. Endotoxin tolerance induction was defined by a reduced
      capacity of monocytes to respond to lipopolysaccharide (LPS) activation following
      a first exposure to LPS. RESULTS: In FMF patients, we observed upregulation of
      neutrophil and monocyte phagocytic activity and oxidative burst during remission
      and downregulation of phagocytic activity and stimulus-dependent oxidative burst
      during an attack. A comparative analysis of oxidative burst has revealed that
      while the neutrophil population shows a certain periodicity in the increase
      (during remission) and decrease (during attacks) in the spontaneous and inducible
      respiratory burst, periodicity in the monocyte population is very poor. In
      addition, LPS-induced oxidative burst and CD11a/CD18 integrin surface expression
      is higher in patients during an attack compared to patients in remission. The
      induction of homologous tolerance of monocytes to the repeated action of LPS is
      observed in FMF patients during an attack, normal donors and patients with BD,
      whereas monocytes from patients in remission failed to induce LPS homologous
      tolerance and exhibited heightened sensitivity to bacterial endotoxin. We found
      that colchicine is able to restore impaired LPS homologous tolerance induction in
      FMF patients in remission upon increased synthesis of IL-4 in FMF patient
      monocytes. CONCLUSION: Chronic inflammation during FMF is characterized by
      periodic changes in monocyte and neutrophil activation and heightened sensitivity
      to endotoxin, which is associated with the episodic nature of FMF. Increased
      endotoxin sensitivity in the period of remission could result from a shift in the
      monocyte activation program from 'alternatively' into 'classically' activated
      monocytes, which may have important implications for the treatment of FMF.

PMID- 16785766
TI  - How wild-type TP53 is inactivated in undifferentiated-type gastric carcinomas:
      analyses of intratumoral heterogeneity in deletion and mutation of TP53.
AB  - OBJECTIVE: In undifferentiated-type gastric carcinoma (UGC), inactivation of TP53
      is infrequent at early stages and comparable to tubular adenocarcinomas (TUBs) at
      advanced stages. To clarify how TP53 inactivation relates to histogenesis of
      UGCs, we examined p53 alterations in multiple samples of individual UGCs.
      METHODS: We used 27 UGCs including 12 mixed types with minor tubular component
      (TC) and 16 with a layered structure (LS), a histological remnant of incipient
      signet ring cell carcinoma (SIG). We examined p53 expression
      immunohistochemically and analyzed loss of heterozygosity (LOH) with four
      microsatellite markers within 17p13.1 in multiple microdissected samples. DNA
      sequence of mutation hot spots in TP53 was determined in representative samples
      of each tumor. RESULTS: In the mixed-type UGCs, 5 and 1 of the 8 tumors without
      LS showed global and regional loss of wild-type TP53, respectively, through
      mutation and LOH, and one fourth of the tumors with LS showed the regional loss.
      In the tumors with the mutation, the mutation pattern was identical between TC
      and poorly differentiated major component. CONCLUSION: The inactivation of wild
      type TP53 is an earlier event before dedifferentiation of TUB to mixed-type UGC,
      but is less frequent and a later event in a subset of mixed-type UGC deriving
      from SIG. .

PMID- 16785767
TI  - D2-40: a reliable marker in the diagnosis of pleural mesothelioma.
AB  - OBJECTIVE: Malignant mesotheliomas of the pleura, peritoneum and pericardium can
      easily be confused with either metastatic adenocarcinomas or reactive pleural
      lesions. D2-40, a monoclonal antibody used as a marker for seminomatous germ cell
      tumours and lymphatic endothelial cells, was recently described in mesothelial
      cells and type I but not type II pneumocytes. METHOD: The immunoreactivities of
      D2-40 in 76 lung carcinomas of different histological types (adenocarcinomas,
      squamous cell, small cell, and bronchioloalveolar carcinomas) were compared with
      those of 36 pleural epithelioid and sarcomatoid mesotheliomas and 5 specimens of
      chronic pleuritis. RESULTS: While all 18 analysed epithelioid mesotheliomas
      displayed a strong membranous immunostaining, 18 sarcomatoid mesotheliomas showed
      no, or a merely faint, cytoplasmic signal, comparable with fibroblasts in chronic
      pleuritis. Out of all analysed lung carcinomas, 49 showed no immunoreactivity for
      D2-40 (64%), while the other 27 (36%) showed a focal weak to moderate and only
      cytoplasmic signal. CONCLUSIONS: We regard D2-40 as a valid marker in the
      differential diagnosis of epithelioid mesotheliomas versus pulmonary
      adenocarcinomas. However, this marker may not properly label sarcomatoid
      mesotheliomas or distinguish them from reactive pleural lesions.

PMID- 16785768
TI  - Curiosity and crisis.

PMID- 16785769
TI  - The intellectual crisis of psychiatric research.
AB  - The aim of this paper was to examine the intellectual crisis and the potential
      sources of reveille in clinical research in psychiatry. Current prevailing
      conceptual models in psychiatry are critically examined, with particular
      reference to neurobiology, clinical psychopharmacology, assessment, and the
      therapeutic process. Biological reductionism, neglect of individual responses to
      treatment, massive propaganda from the pharmaceutical industry, misleading
      effects of psychometric theory on clinical assessment, and lack of consideration
      of multiple therapeutic ingredients and of the role of psychological well-being
      are identified as major sources of an intellectual crisis in psychiatric
      research. The conceptual crisis of psychiatry is shared by other areas of
      clinical medicine and stems from a narrow concept of science that neglects
      clinical observation, the basic method of medicine. A unified concept of health
      and disease may yield new clinical insights in psychiatric disorders, and may
      result in therapeutic efforts of more enduring quality than current strategies.

PMID- 16785770
TI  - Interpersonal psychotherapy for somatizing patients.
AB  - The interpersonal model is important for understanding somatizing behavior.
      According to this model, somatizing behavior is a form of interpersonal
      communication driven by insecure attachment. Interpersonal psychotherapy (IPT) is
      a time-limited, manual-based treatment designed to relieve symptoms and improve
      interpersonal functioning. Based on our experience using IPT with somatizing
      patients, we recommend a series of strategies for its successful implementation.
      These strategies include an emphasis on the therapeutic alliance within a
      bilaterally negotiated treatment contract, and aiming for improvement in
      interpersonal functioning rather than for alleviation of physical symptoms.
      Specific techniques include the use of bridging metaphors, communication
      analysis, and genuine positive reinforcement. With a focus on communication in a
      time-limited frame, fostered by a strong collaborative relationship, IPT appears
      to be a promising method of reducing somatizing behavior. We urge further
      research on the efficacy of this form of therapy.

PMID- 16785771
TI  - Comparison of sleep condition and sleep-related psychological activity after
      cognitive-behavior and pharmacological therapy for chronic insomnia.
AB  - BACKGROUND: Previous studies of insomnia focused mainly on the improvement of
      sleep condition and ignored the effects of sleep-related psychological activity
      and daytime function after pharmacological and behavioral treatments. We compared
      the clinical effects of both therapies on sleep condition, sleep-related
      psychological activity and daytime function in chronic insomnia. METHODS: Seventy
      one patients with chronic insomnia were randomly divided into 4 groups and either
      received cognitive-behavior therapy (CBT, n = 19), pharmacological therapy (PCT,
      n = 17), CBT plus medication (Combined, n = 18) or placebo (n = 17). The
      treatments lasted for 8 weeks with follow-ups conducted at 3 and 8 months. On the
      day after treatment ended, all patients were assessed using a polysomnogram
      (PSG), a sleep diary and a psychological assessment. RESULTS: The three active
      treatments were more effective than placebo at the time the treatments were
      completed. Subjective sleep-onset latency, sleep efficacy and total sleep time
      were better in the PCT group than in the CBT group. At the 3-month follow-up,
      subjective and objective sleep-onset latency, sleep efficacy and total sleep time
      were better in the CBT group than in both the PCT and the Combined group. At the
      8-month follow-up, the CBT group showed a steady comfortable sleep state, while
      the PCT and Combined groups were gradually returning to the pre-treatment
      condition. The Combined group showed a variable long-term effect. On the other
      hand, pre-sleep arousal at nighttime, dysfunctional beliefs about sleep as well
      as daytime functioning in the CBT group not only improved, but was better than in
      the other active treatment groups. CONCLUSION: Medication and Combined therapy
      produced a short-term effect on chronic insomnia while CBT had a long-term effect
      of improved sleep-related psychological activity and daytime functioning.

PMID- 16785772
TI  - Differential predictors of response to preventive cognitive therapy in recurrent
      depression: a 2-year prospective study.
AB  - BACKGROUND: Major depressive disorder is a recurrent disease. Brief cognitive
      therapy (CT), added to either regular care or medication, is helpful in
      preventing relapse/recurrence. Little is known which type of persons benefit from
      preventive CT, the so called 'aptitude treatment interaction' effect. METHOD: The
      present cohort included exclusively patients with at least two previous episodes
      remitted on various types of treatments (n = 172). They were assessed within a
      clinical trial comparing treatment as usual (TAU) with preventive CT added to
      TAU. Differential demographic, illness-related, psychological and biological risk
      factors in postponing recurrence by preventive CT were examined. RESULTS:
      Significant aptitude-treatment-interaction effects were found for the number of
      previous episodes, daily hassles and life events, avoidant coping, gender, and
      morning cortisol levels. Preventive CT seemed ineffective in patients with life
      events (as more frequently reported by women in our study) and in patients with
      high episode number characterized by higher levels of avoidant coping. Generic
      predictors indicate that in CT, as in TAU, patients with more residual depressive
      symptomatology and higher levels of dysfunctional attitudes profit less from
      preventive CT. CONCLUSION: The finding that preventive CT protects against the
      influence of a consistently found risk factor of relapse/recurrence, i.e. the
      number of depressive episodes, underlines the potential of psychological
      preventive interventions. Preventive CT seemed to be especially effective in
      reducing presumably internally provoked, relapse/recurrence but may be quite
      ineffective in reducing externally provoked relapse/recurrence. CT possibly
      prevents either stress generation or disrupts kindling effects. Kindling effects
      probably cannot be disrupted in patients with higher levels of avoidant coping
      who experienced a high number of episodes, and patients who experienced life
      events.

PMID- 16785773
TI  - Pregnant women with bronchial asthma benefit from progressive muscle relaxation:
      a randomized, prospective, controlled trial.
AB  - BACKGROUND: Asthma is a serious medical problem in pregnancy and is often
      associated with stress, anger and poor quality of life. The aim of this study was
      to determine the efficacy of progressive muscle relaxation (PMR) on change in
      blood pressure, lung parameters, heart rate, anger and health-related quality of
      life in pregnant women with bronchial asthma. METHODS: We treated a sample of 64
      pregnant women with bronchial asthma from the local population in an 8-week
      randomized, prospective, controlled trial. Thirty-two were selected for PMR, and
      32 received a placebo intervention. The systolic blood pressure, forced
      expiratory volume in the first second, peak expiratory flow and heart rate were
      tested, and the State-Trait Anger Expression Inventory and Health Survey (SF-36)
      were employed. RESULTS: According to the intend-to-treat principle, a significant
      reduction in systolic blood pressure and a significant increase in both forced
      expiratory volume in the first second and peak expiratory flow were observed
      after PMR. The heart rate showed a significant increase in the coefficient of
      variation, root mean square of successive differences and high frequency ranges,
      in addition to a significant reduction in low and middle frequency ranges. A
      significant reduction on three of five State-Trait Anger Expression Inventory
      scales, and a significant increase on seven of eight SF-36 scales were observed.
      CONCLUSIONS: PMR appears to be an effective method to improve blood pressure,
      lung parameters and heart rate, and to decrease anger levels, thus enhancing
      health-related quality of life in pregnant women with bronchial asthma.

PMID- 16785774
TI  - Dose response to adjunctive light therapy in citalopram-treated patients with
      post-stroke depression. A randomised, double-blind pilot study.
AB  - BACKGROUND: Post-stroke depression affects the outcome of stroke rehabilitation
      and is observed in approximately 30% of all stroke patients. We investigated
      whether the addition of light treatment to medical antidepressants influences the
      course of depression as measured by the Hamilton Depression Scale. METHODS: The
      effect of a combination of light therapy and citalopram in stroke victims
      receiving citalopram was examined by use of two different doses of light therapy
      under double-blind conditions. Altogether, 63 patients were included in the
      study. The mean age was 74.9 years. RESULTS: After 4 weeks of therapy, the 6-item
      subscale of the Hamilton Depression Scale showed a statistically significantly
      larger improvement in patients receiving high-intensity light treatment compared
      to those treated with medium-intensity light (p < 0.05). CONCLUSION: This pilot
      study demonstrates a dose response effect of light used as an adjunct therapy to
      antidepressants in post-stroke patients with major depression.

PMID- 16785775
TI  - Performance of the pictorial representation of illness and self measure in
      individuals with alcohol dependence, alcohol abuse or at-risk drinking.
AB  - BACKGROUND: The impact of chronic illnesses is not only influenced by one's
      physical functioning but also by its subjective importance to the individual's
      life. However, it is often difficult to asses such an impact in an appropriate
      way. PRISM (pictorial representation of illness and self measure) measures the
      perception of illness and first data on its validity have been published. The aim
      of the present study was to prove the applicability of PRISM regarding alcohol
      dependent patients. Therefore, a comparison was made between alcohol-dependent
      patients, alcohol abusers and at-risk drinkers. METHOD: The sample consisted of
      763 general practice patients, who scored above the cutoff in alcohol-related
      screening questionnaires. Of this sample, 330 were diagnosed as alcohol
      dependent, alcohol abusers (both according to DSM-IV) or at-risk drinkers. To
      prove the applicability, PRISM was put in context with the severity of alcohol
      dependence and the core constructs of the transtheoretical model of behavior
      change. RESULTS: PRISM was related to the severity of the drinking problem: the
      severer the drinking problem, the shorter the distance between self and illness.
      High correlations with aspects of alcohol consumption - such as adverse
      consequences from drinking, temptation to drink, and self-efficacy to abstain -
      were found. Concerning stages of change according to the transtheoretical model
      of behavior change, data show a significant difference in the self-illness
      separation between patients in the stage of contemplation compared to those in
      the precontemplation or action stage. CONCLUSIONS: The PRISM task is applicable
      to patients with alcohol use disorders. Within this group and in contrast to
      other chronic diseases, PRISM reveals a significant relationship not only to the
      severity of drinking, but also to the readiness to change one's drinking
      behavior.

PMID- 16785776
TI  - Metacognitive therapy versus exposure and response prevention for pediatric
      obsessive-compulsive disorder. A case series with randomized allocation.
AB  - BACKGROUND: Exposure with ritual prevention (ERP) is the psychotherapeutic
      treatment of choice for pediatric obsessive-compulsive disorder (OCD). In the
      present study, a new treatment rationale - metacognitive therapy (MCT) for
      children - was developed and evaluated. METHODS: Ten children and adolescents
      with OCD were randomly assigned to either MCT or ERP therapy condition. Patients
      were assessed before and after treatment and at the 3-month and 2-year follow-up
      by means of symptom severity interviews. Depressive symptoms were also assessed.
      Manualized treatment involved up to 20 sessions on a weekly basis. RESULTS: We
      found clinically and statistically significant improvements in symptom severity
      after treatment. At the 3-month and 2-year follow-up, the attained improvements
      during treatment were retained. CONCLUSIONS: Despite some methodological
      limitations, results showed that MCT proved to be a promising psychotherapeutic
      alternative to the well-established ERP in the treatment of pediatric OCD.
      Further investigations into the efficacy of MCT are necessary to answer questions
      as to the working mechanisms underlying therapy for OCD.

PMID- 16785777
TI  - Accelerated healing of excisional skin wounds by PL 14736 in alloxan
      hyperglycemic rats.
AB  - PL 14736 is a synthetic peptide, originally isolated from human gastric juice,
      that has anti-inflammatory and tissue-protective actions in experimental models
      of gastrointestinal inflammation. To investigate its possible benefit in poorly
      healing skin wounds, the effects of the topical application of PL 14736 in a gel
      formulation have been studied on full-thickness excisional wounds in rats, either
      healthy or made hyperglycemic by alloxan (175 mg/kg s.c.) 5 days previously. The
      effects of becaplermin gel (platelet-derived growth factor, PDGF-BB, Regranex, a
      standard therapy for diabetic foot ulcers, were investigated for comparison.
      Healing was evaluated for up to 7 days after wounding, using digital planimetry
      analysis, macroscopic scoring and histology. While healing was too rapid in
      healthy rats to observe enhancement by either treatment, in the hyperglycemic
      rats which exhibited delayed healing, PL 14736 (10-1,000 microg/wound) produced a
      dose-dependent acceleration of wound healing (determined by macroscopic scoring)
      equivalent at the highest doses to that observed with becaplermin. The beneficial
      effect on healing was associated with increased deposition of organized
      granulation tissue by day 7 for both PL 14736 and becaplermin, as determined
      histologically. PL 14736 tended to have a greater effect than becaplermin on the
      formation of granulation tissue containing mature collagen. Wound contraction, as
      measured by planimetry, was not significantly affected. In conclusion, topical PL
      14736 produces a dose-dependent acceleration of deficient skin wound healing in
      hyperglycemic rats by facilitating granulation tissue formation, similar to the
      response seen with topical becaplermin, the standard therapy for diabetic skin
      wounds. PL 14736 may represent an alternative therapy for delayed wound healing,
      such as that seen with diabetic foot ulcers, without the proliferative concerns
      or immunogenicity associated with growth factors.

PMID- 16785778
TI  - HER-2/neu in breast cancer: a comparative study between histology,
      immunohistochemistry, and molecular technique (FISH).
AB  - HER-2/neu is a protooncogene frequently overexpressed in breast cancer.
      Fluorescence in situ hybridization (FISH) is a technique targeting the gene
      amplification, while immunohisto-chemistry detects the protein expression.
      Usually both are applied to paraffin-embedded tissue. The authors studied HER-2
      by FISH and immunohistochemistry (HercepTest) in 81 breast carcinomas. The
      results showed an overall concordance (correlation coefficient 0.64). In all
      cases with HercepTest score 0 and 1+, nonamplification of the gene was observed.
      Gene amplification was found in 20% of cases with a 2+ score and in 77.78% of
      cases with a 3+ score. Data described in literature for 3+ carcinomas showed a 3%
      to 10% discrepancy between protein expression and gene amplification, while in
      this study this difference was up to 22.22%. As a consequence, even if it is
      usually considered important to analyze only 2+ cases by FISH, 3+ scores
      nonamplified for HER-2/neu may be a new, interesting subset. Furthermore, the
      authors investigated the two-variables correlation between chromosome 17 copy
      number, protein over-expression, gene amplification, and presence of metastatic
      lymph nodes. Interesting results came from the correlation between the HercepTest
      score and the HER-2/neu gene amplification evaluation, HercepTest and chromosome
      17 aneusomy, and gene amplification and lymph nodes status. In conclusion, the
      FISH technique can be an important and useful diagnostic tool to integrate the
      results of the HercepTest and to select patients for immunotherapy.

PMID- 16785779
TI  - HER-2 status in breast cancer: correlation of gene amplification by FISH with
      immunohistochemistry expression using advanced cellular imaging system.
AB  - It has become important to accurately evaluate the status of HER-2/neu in
      invasive breast cancer, especially when one is considering the use of anti-HER-2
      monoclonal antibody therapy (Trastuzumab). Almost one third of invasive breast
      carcinomas overexpress the HER-2/neu protein, so the use of the anti-HER-2/neu
      monoclonal antibody Herceptin (trastuzumab) to block the protein has become
      important in the management of and in prolonging the survival for patients with
      metastatic breast cancer. The effectiveness of this therapy is dependent on
      accurately evaluating the HER-2 status in these tumors, which can be done either
      by studying the expression of HER-2 protein by immunohistochemistry (IHC) or by
      evaluating HER-2 gene amplification by fluorescent in situ hybridization (FISH).
      Since interobserver variability may occur in manually grading HER-2 protein
      expression by IHC, the aim of this study was to compare the HER-2/neu expression
      by IHC using a computer-based image analysis system with that of the gene
      amplification by FISH. Formalin-fixed paraffin-embedded archival tissue from 108
      primary infiltrating ductal carcinomas were immunostained using the HercepTest
      (DAKO). To reduce interobserver variability, membrane staining was evaluated
      using the Automated Cellular Imaging System (ACIS) by ChromaVision, and the cases
      were divided into four groups: group 1 (n=23) with HER-2/neu expression ACIS
      score less than or equal to 1.5; group 2 (n=17) with a score ranging from 1.6 to
      1.9; group 3 (n=46) with a score 2.0 to 2.5; and group 4 (n=22) with a score
      greater than or equal to 2.6. FISH was performed on all of the 108 cases using
      the PathVysion HER-2/neu DNA probe kit from Vysis Inc. All cases were also
      manually reviewed and graded as negative, 1+, 2+, and 3+ according to the DAKO
      HercepTest grading scheme. Cases with negative and 1+immunostaining were
      considered as HER-2 not overexpressed, and cases with 2+ and 3+ staining were
      classified as showing HER-2 overexpression. In group 1, 1 of 23 (4%), in group 2,
      2 of 17 (12%), in group 3, 5 of 46 (11%), and in group 4, 19 of 22 (86%) cases
      showed gene amplification by FISH. Furthermore, in group 4 all 15 (100%) cases
      with an ACIS score of 3 or greater were FISH positive. Correlation with manual
      IHC score and FISH showed that 2 of the 23 (9%) IHC negative (0 and 1+) cases and
      25 of the 85 (29%) IHC positive (2+ and 3+) cases showed gene amplification by
      FISH. This study shows that the amplification of the HER-2/neu gene correlates
      better with overexpression of the HER-2/neu protein by IHC when the score is
      either less than 1.5 or greater than 2.6 by ACIS. Therefore, FISH may be useful
      to better evaluate HER-2/neu status in breast cancer in cases where the ACIS
      score by immunohistochemistry is 1.6 to 2.5, and since the correlation is so
      good, FISH may not be needed for HER-2 evaluation in cases with ACIS scores less
      than 1.5 and greater than 2.6.

PMID- 16785780
TI  - HER2 is unlikely to be involved in directly regulating angiogenesis in human
      breast cancer.
AB  - Angiogenesis is a fundamental component of oncogenesis. Angiogenic factors such
      as vascular endothelial growth factor (VEGF) and platelet derived-endothelial
      cell growth factor/thymidine phosphorylase (PD-ECGF/TP) are generated from tumor
      cells to provide tumor growth and are thought to be regulated via the HER2
      oncogene, whose amplification is the most common genetic alteration in breast
      cancer. The present study aimed to evaluate the immunoreactivity of angiogenic
      factors (VEGF, PD-ECGF/TP) and microvessel density (MVD) via epidermal growth
      factor receptor (EGFR) and HER2, and to correlate their expression with
      clinicopathologic features. Two hundred one invasive human breast cancer
      specimens were tested immunohistochemically for the expression of these proteins.
      In addition, MVD was examined using computerized image analysis. VEGF could be an
      additional interesting prognostic variable, as it was significantly associated
      with tumor grade (P=0.002), stage (P=0.018), and negative estrogen receptor
      status (P=0.011). EGFR was significantly related to invasive ductal carcinoma
      (P=0.030), tumor grade (P=0.009), VEGF expression (P=0.013), PD-ECGF/TP
      expression (P=0.024), and MVD (P=0.050). The finding that VEGF is not correlated
      to MVD does not rule out a crucial role of VEGF as a key factor in angiogenesis.
      HER2 could not be correlated to MVD, VEGF expression, or PD-ECGF/TP expression,
      indicating that this factor is unlikely to be involved in directly regulating
      angiogenesis, whereas the significant correlations between EGFR and histologic
      tumor type, tumor grade, the angiogenic factors VEGF and PD-ECGF/TP, and MVD
      point out that EGF is the major modulating growth factor for angiogenesis in
      breast cancer.

PMID- 16785781
TI  - LKB1 protein expression in human breast cancer.
AB  - Peutz-Jeghers syndrome is caused by germline mutations in the LKB1/STK11 gene.
      Peutz-Jeghers syndrome is associated with an increased risk of developing
      intestinal and extraintestinal cancers, including pancreatic, lung, and breast
      carcinomas. LKB1 gene inactivation has recently been demonstrated in a subset of
      sporadic pancreatic and lung carcinomas. The role of the LKB1 gene in sporadic
      breast carcinomas remains unclear, though recent studies suggest inactivation
      only within papillary carcinomas. Using a commercially available polyclonal
      antibody that has been shown to mirror LKB1 genetic status in gastrointestinal
      and pulmonary carcinomas, the authors performed IHC on a large series of breast
      cancers using tissue microarrays (TMAs). All abnormal TMA results were confirmed
      using whole sections; specifically, whole sections from the donor blocks of
      lesions demonstrating diminished or absent LKB1 protein expression on TMA were
      evaluated to compare labeling of the lesion with that of the surrounding normal
      breast. In all cases, normal breast epithelium demonstrated strong cytoplasmic
      labeling (providing an internal positive control), whereas the stroma was
      nonreactive. Luminal cells typically labeled more strongly than myoepithelial
      cells. Among 70 invasive ductal carcinomas, 3 (4.3%) showed complete loss of LKB1
      labeling, whereas 6 others (8.6%) showed diminished labeling. Of the eight
      intraductal carcinoma lesions adjacent to these invasive carcinomas, one (12.5%)
      showed complete loss of LKB1 labeling and one other (12.5%) showed diminished
      labeling; these results were identical to those of the adjacent invasive
      carcinomas. One of 10 (10%) hematogenous metastases of mammary carcinoma showed
      loss of LKB1 labeling. Nine of the 10 invasive carcinomas and both of the ductal
      carcinoma in situ (DCIS) cases showing loss of or diminished LKB1 expression were
      of high grade. In contrast, all 13 pure nonpapillary DCIS lesions, all 5 invasive
      lobular carcinomas and 3 accompanying lobular carcinoma in situ lesions, all 7
      papillary DCIS lesions, and all 3 papillomas evaluated showed intact LKB1
      labeling. Therefore, although frequent methylation of the LKB1 gene has been
      reported in papillary carcinomas of the breast, the authors did not find loss of
      protein expression in these lesions. Instead, it was found that loss of LKB1
      protein expression occurs in a subset of high-grade in situ and invasive mammary
      carcinomas. The authors found LKB1 gene methylation in several of these invasive
      carcinomas. Given recent Western blot results indicating that diminished LKB1
      expression in breast carcinomas correlates with shorter relapse-free survival,
      LKB1 IHC merits evaluation as a potential prognostic marker for breast carcinoma.

PMID- 16785782
TI  - B-cell chronic lymphocytic leukemia: correlation of clinical stages with
      angiogenic cytokine expression.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation
      of non-cycling B cells in lymphatic and extralymphatic tissues. Earlier studies
      had validated that angiogenesis was increased in B-CLL. Increased serum
      concentrations of vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) connote a poor prognosis in early-stage B-CLL. Early
      progression is also related to transforming growth factor-beta (TGF-beta), which
      inhibits B-cell proliferation and immunoglobulin production. The authors
      investigated the expression of CD34, VEGF, bFGF, and TGF-beta and their receptors
      in different stages of B-CLL by analyzing bone marrow samples from 23 patients
      (11 with Rai stages 0-II; 12 with stages III or IV). TGF-beta2 was expressed more
      strongly in stages 0 to II than in stages III or IV (P=0.03). There was no
      significant difference in the intensity of CD34, TGF-beta1, VEGF, and bFGF and
      their receptors between stages 0 to II and stages III or IV. Staining showed bFGF
      expression to be stronger than VEGF expression (P=0.001). Results did not confirm
      an association between the intensity of angiogenesis and B-CLL stage. The
      expression of TGF-beta2 was stronger in early-stage disease and may help slow
      disease progression.

PMID- 16785783
TI  - Downregulation of TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L in
      Barrett's esophagus with dysplasia and adenocarcinoma.
AB  - TRAIL/Apo2L is a CD95 ligand-related member of the TNF family that initiates
      apoptosis in immune and neoplastic cells after binding to specific surface
      receptors. The authors previously reported a specific topographic pattern of
      TRAIL expression in the normal colonic mucosa and the loss of TRAIL expression in
      tubular adenomas as well as in most colon carcinomas. Therefore, they
      hypothesized that similar changes may occur during the malignant transformation
      of Barrett's esophagus. The aim of this study was to compare TRAIL/Apo2L
      expression in normal gastroesophageal (GE) junction, Barrett's esophagus with and
      without dysplasia, and associated adenocarcinoma. Immunohistochemical evaluation
      of TRAIL expression was performed on formalin-fixed paraffin-embedded sections
      from 29 GE junction/esophageal biopsies, 20 gastric biopsies, 6 esophagectomies,
      2 small bowel resection specimens, and 5 colon biopsies. The expression was
      graded semiquantitatively on a 4-point scale (0-3). TRAIL was expressed in the
      foveolar epithelium of the histologically normal GE junctional mucosa and stomach
      as well as in the normal intestinal epithelium, with maximal expression in the
      surface epithelium. TRAIL was always detected in Barrett's metaplasia (21/21,
      100%), and the overall expression was similar to that of the columnar portion of
      the normal GE junction (8/8, 100%). TRAIL was rarely and weakly (1+) expressed in
      Barrett's esophagus with dysplasia (3/18, 16.7%) and adenocarcinoma (1/10, 10.0%)
      (P<0.001). Similarities in the topographic pattern of TRAIL expression in the
      normal GE junction, stomach, small intestine, and colon suggest a common function
      of TRAIL throughout the gastrointestinal tract. These results show that the
      downregulation of TRAIL is associated with development of dysplasia in Barrett's
      esophagus. Thus, the immunohistochemically detected downregulation of TRAIL
      expression appears to be a promising indicator of dysplasia in Barrett's
      esophagus.

PMID- 16785784
TI  - Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon
      cancer correlates with reduced apoptosis competence.
AB  - Pms2 protein is a component of the DNA mismatch repair complex responsible both
      for post-replication correction of DNA nucleotide mispairs and for early steps in
      apoptosis. Germline mutations in DNA mismatch repair genes give rise to
      hereditary non-polyposis colon cancer, which accounts for about 4% of colon
      cancers. However, little is known about the expression of mismatch repair
      proteins in relation to sporadic colon cancer, which accounts for the great
      majority of colon cancers. Multiple samples were taken from the non-neoplastic
      flat mucosa of colon resections from patients with no colonic neoplasia, a
      tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed
      using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome
      stained epoxy sections using morphologic criteria. Samples from patients without
      colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the
      base of crypts, while samples from 2 of the 3 colons with a tubulovillous
      adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2
      expression. Samples from patients with an adenocarcinoma that had reduced Pms2
      expression also exhibited reduced apoptosis capability in nearby tissue samples,
      evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced
      Pms2 expression in the colonic mucosa may be an early step in progression to
      colon cancer. This reduction may cause decreased mismatch repair, increased
      genetic instability, and/or reduced apoptotic capability. Immunohistochemical
      determination of reduced Pms2 expression, upon further testing, may prove to be a
      promising early biomarker of risk of progression to malignancy.

PMID- 16785785
TI  - Expression of CD138 (Syndecan-1) in renal cell carcinoma is reduced with
      increasing nuclear grade.
AB  - CD138/Syndecan-1 is a cell-surface heparan sulfate proteoglycan expressed on most
      epithelial cells, and decreased CD138 expression is associated with increased
      invasive and metastatic potential in carcinomas. CD138 expression has not been
      investigated previously in renal neoplasms. Formalin-fixed, paraffin-embedded
      tissue sections of 50 renal cell carcinomas (RCCs) (40 clear-cell RCCs of various
      nuclear grades, 10 of which harbored metastases; 6 papillary RCCs, 4 chromophobe
      RCCs) and 4 oncocytomas were stained immunohistochemically for CD138 using the
      monoclonal antibody B-B4 (CD138). Staining intensity and distribution were scored
      and results related to histologic type, nuclear grade, and local stage (pT).
      Immunoreactivity was membranous in all clear-cell RCCs, chromophobe RCCs, and
      oncocytomas and was located at the basal aspect of cytoplasm in papillary RCCs.
      In clear-cell RCCs, the extent of CD138 immunoreactivity decreased with
      increasing nuclear grade (P<0.001). No significant correlation was found between
      CD138 immunoreactivity and histologic type (P=0.2) or local stage (P=0.7).
      Metastatic foci showed a mild to moderate decrease in intensity compared with
      primary tumor. Decreased expression of CD138 may have a role in more aggressive
      behavior of clear-cell RCC.

PMID- 16785786
TI  - Cutaneous metastasis of renal cell carcinoma with Zellballen-like inflammatory
      reaction pattern on immunohistochemical studies.
AB  - Skin tumors show variable infiltration by subtypes of inflammatory cells. The
      composition of these cellular infiltrates, particularly tumor-associated
      macrophages and dendritic cell numbers, may be responsible for skin tumor
      progression or regression. In addition, these cells may give rise to diagnostic
      dilemmas on immunohistochemical studies. The authors report on the local
      inflammatory reaction to a metastatic renal cell carcinoma to the skin.
      Histologic examination and immunohistochemical studies demonstrated zellballen
      like changes with S-100-positive spindled cells identified around and within
      tumor cell nests. The role of tumorassociated macrophages and dendritic cells in
      the skin is discussed.

PMID- 16785787
TI  - HER-2/neu and bcl-2 in ovarian carcinoma: clinicopathologic, immunohistochemical,
      and molecular study in patients with shorter and longer survival.
AB  - The bcl-2 protein is a membrane protein involved in prolonging cell survival by
      inhibiting apoptosis. The HER-2 oncogene, which is located on chromosome 17 and
      encodes for a tyrosine-kinase growth factor receptor, is amplified and HER-2/neu
      is overexpressed in 25% to 30% of breast carcinomas. The authors analyzed the bcl
      2 expression and the bcl-2 gene and HER-2/neu overexpression and amplification in
      FIGO stage IIIC, serous, G3, ovarian carcinomas obtained from living patients who
      had no evident disease 5 years after primary treatment compared with ovarian
      carcinomas obtained from patients, matched for stage, grade of differentiation,
      and treatment, who had died of progression of disease no later than 2 years after
      primary treatment. bcl-2 overexpression was statistically correlated with
      progression of disease during first-line chemotherapy (P=0.021). The HER-2/neu
      status was found not to correlate with progression of disease during first-line
      chemotherapy. Both bcl-2 and HER-2/neu expression were not statistically
      associated with the clinical outcome of ovarian cancer patients. Gene
      amplification of the HER-2/neu chromosome 17 was found in all the HER-2/neu, 3+
      score, positive-staining ovarian carcinomas. None of the analyzed samples
      revealed a translocation t(14;18)(q32;q21) in the bcl-2 gene. The knowledge of
      additional prognostic or even predictive factors, such as bcl-2 expression, in
      patients with advanced ovarian carcinoma before the primary chemotherapeutic
      treatment may help in the management of patients who require a more tailored
      treatment. In addition, the gene amplification of the HER-2/neu suggests that HER
      2 is a potential target for treatment in ovarian cancer.

PMID- 16785788
TI  - GLUT-1 is preferentially expressed in atypical endometrial hyperplasia and
      endometrial adenocarcinoma.
AB  - The facilitative transport of monosaccharides in human cells is accomplished by a
      family of transmembrane proteins, GLUT-1 to GLUT-7, that differ in their tissue
      distribution, affinities for specific monosaccharides, and physiologic
      regulation. GLUT-1, a high-affinity glucose transporter, is normally expressed in
      erythrocytes, the perineurium of peripheral nerves, and capillary endothelial
      cells of the blood-brain barrier. Although the aberrant expression of GLUT-1 has
      been reported in a wide spectrum of epithelial malignancies, its possible
      correlation with the malignant transformation of endometrial epithelium has not
      been clearly established. The purpose of this study was to evaluate the extent to
      which benign, hyperplastic, atypical, and malignant endometrial epithelia express
      GLUT-1. The authors examined the IHC expression of GLUT-1 in cases of
      proliferative endometrium (n=12), secretory endometrium (n=10), endometrial
      polyps (n=10), adenomyosis (n=18), simple hyperplasia (n=14), complex hyperplasia
      without atypia (n=17), complex hyperplasia with atypia (n=17), and adenocarcinoma
      (n=31). Positive staining was defined as distinct, linear membrane staining,
      particularly at cell-cell borders. Cells that showed only cytoplasmic staining
      were considered negative. The percentages of positive cells and staining
      intensity were assessed in a semiquantitative fashion and scored (1+ to 3+). All
      cases from proliferative endometrium, secretory endometrium, adenomyosis, and
      simple hyperplasia and 90% (9/10 cases) of the endometrial polyps were negative
      for GLUT-1. GLUT-1 was expressed in 24% (4/17 cases) of complex hyperplasia
      without atypia, 71% (12/17 cases) of complex hyperplasia with atypia, and 90%
      (28/31 cases) of adenocarcinomas. The extent of staining ranged from occasional
      positive foci to extensive multifocal staining. GLUT-1 positivity increased in
      intensity as the distance of tumor cells to stroma increased. The authors
      conclude that GLUT-1 is preferentially expressed in complex hyperplasia with
      atypia and in adenocarcinoma and that GLUT-1 immunostaining is useful in
      distinguishing benign hyperplasia from hyperplasia strongly associated with
      malignancy. GLUT-1-mediated glucose transport may allow hypoxic tumor cells
      distant from stromal blood vessels to survive through glycolysis. These data
      suggest that the expression of GLUT-1 transporter may be closely related to the
      malignant transformation of epithelial endometrial tumors by supporting their
      increased need for glucose metabolism.

PMID- 16785789
TI  - Immunohistochemical analysis of embryonal sarcoma of the liver.
AB  - Embryonal sarcoma of the liver is a rare, aggressive malignant tumor that
      typically occurs in children and teenagers. Microscopic features include spindle,
      oval, or stellate cells with poorly defined cell borders, nuclear pleomorphism
      and multinucleation, and variable immunoreactivity to cytokeratin, vimentin, and
      alpha-1-antitrypsin. Intracellular and extracellular PAS-positive, diastase
      resistant hyaline globules are commonly present. The authors evaluated a panel of
      IHC stains to better define the pattern of immunoreactivity in this tumor.
      Embryonal sarcomas of the liver were identified from archival files and were
      immunostained with antibodies: cytokeratin AE1/3, hepatocyte, SMMS, myogenin,
      calponin, h-caldesmon, desmin, S100, vimentin, CD34, C-kit (CD117), CD10, ALK-1,
      PE10, Bcl2, p53, and Ki-67. Six cases were identified. Patient age ranged from 6
      to 24 years. Tumors ranged from 10 to 20 cm and contained spindled and
      epithelioid areas with PAS-positive, diastase-resistant globules and atypical
      cells with focal multinucleation. All cases showed immunoreactivity with vimentin
      and five showed immunoreactivity with Bcl2. Focal immunoreactivity was seen with
      cytokeratin AE1/3 in three cases, CD10 in four, calponin in two, desmin in one,
      and p53 in four. All tumors were negative with hepatocyte, myogenin, CD34, SMMS,
      h-caldesmon, PE10, ALK-1, and S100. No cytoplasmic staining was seen with C-kit.
      The proliferation index ranged from 30% to 95%. The diagnosis of embryonal
      sarcoma is based on typical morphologic features in a large liver tumor occurring
      in a young patient. The most useful IHC stains help to exclude tumors such as
      hepatoblastoma, hepatocellular carcinoma, embryonal rhabdomyosarcoma, and other
      sarcomas.

PMID- 16785790
TI  - Immunohistochemical detection of hTERT protein in soft tissue sarcomas:
      correlation with tumor grade.
AB  - Human telomerase reverse transcriptase (hTERT) is a telomerase catalytic subunit
      that regulates telomerase activity. Telomerase is expressed in many human cancers
      and cell lines and is thought to contribute to their immortality. Little is known
      about the expression of telomerase in non-epithelial tumors. The objective of
      this study was to evaluate hTERT expression in a wide range of soft tissue
      sarcomas. A total of 154 cases of different types of soft tissue sarcoma (54 low
      grade, 40 intermediate-grade, and 60 high-grade cases) were evaluated for hTERT
      expression using immunohistochemistry on tissue microarrays. hTERT
      immunoexpression was detected in 59% of cases; it was observed in 46%, 58%, and
      72% of low-grade, intermediate-grade, and high-grade sarcoma cases, respectively.
      The intensity of staining positively correlated with the grade of the sarcomas:
      diffuse strong positive nuclear staining was identified in 6, 8, and 30 cases of
      low-grade, intermediate-grade, and high-grade sarcomas, respectively. These
      results suggest that telomerase expression is more often detected in highly
      malignant tumors than in low-grade sarcomas and thus may be a critical mechanism
      in tumor progression.

PMID- 16785791
TI  - Comparative study of angiogenesis in thyroid glands with Graves disease and
      Hashimoto's thyroiditis.
AB  - Angiogenesis entails the sprouting of new vessels from pre-existing vasculature.
      In adults, angiogenesis occurs in the thyroid gland during disease processes such
      as hyperplastic goiter, Graves disease, thyroiditis, and cancer. In the present
      study multiple morphologic characteristics of microvessels were measured in and
      compared between 18 cases of Graves disease, 29 cases of Hashimoto's thyroiditis,
      and 15 control cases. All histologic sections were immunostained for CD31.
      Quantification of microvessel density (MVD), major axis length, minor axis
      length, area, perimeter and shape factor was performed by image analysis. MVD was
      increased significantly in both forms of autoimmune thyroid disease.
      Significantly higher values were found in Graves disease in comparison to
      Hashimoto's thyroiditis. In contrast, major axis length, minor axis length, and
      area had significantly higher values in Hashimoto's thyroiditis than in Graves
      disease. The statistical analysis revealed MVD as the unique significant
      morphometric factor discriminating the two autoimmune entities.

PMID- 16785792
TI  - Autoimmune-like pulmonary disease in association with parvovirus B19: a clinical,
      morphologic, and molecular study of 12 cases.
AB  - Parvovirus B19, the agent responsible for fifth disease, has been emerging as a
      significant pathogenetic factor in various acute vasculitic syndromes such as
      Wegener's granulomatosis, Henoch-Schonlein purpura, and Kawasaki disease. It has
      also been implicated in more chronic vasculopathic syndromes, specifically in the
      context of scleroderma and dermatomyositis. The basis of this association is
      likely multifactorial; implicated mechanisms include the virus's affinity for
      endothelium, resulting in a state of neoantigenicity through varied mechanisms as
      well as the induction of tumor necrosis factor alpha, a factor involved in the
      propagation of ANCA-positive vasculitic syndromes. The authors present a series
      of 12 patients with interstitial lung disease including idiopathic pulmonary
      fibrosis, scleroderma-associated pulmonary fibrosis, lymphocytic interstitial
      pneumonitis, and septal capillaritis. In all cases there was evidence of chronic
      parvovirus B19 infection based on serologic assessment and the isolation of B19
      DNA on lung samples in all patients. Furthermore, in two cases there was in situ
      localization of B19 RNA and tumor necrosis factor alpha to endothelium and
      stromal cells. On pathologic examination, there were varying degrees of both
      septal fibrosis and inflammation along with evidence of septal capillary injury.
      In those cases categorized as representing either scleroderma or idiopathic
      pulmonary fibrosis, the immunofluorescent studies showed evidence of anti
      endothelial cell antibody formation. The ANCA-associated syndromes were, as
      expected, negative by fluorescent analysis. Significantly elevated factor VIII
      levels, a standard serologic index of endothelial cell injury, were seen in four
      of the six patients tested. The antiphospholipid profile revealed
      antiphospholipids in 7 of the 11 patients tested. This report highlights a
      possible causal role for parvovirus B19 in the pathogenesis of select pulmonary
      disorders.

PMID- 16785793
TI  - Application of two different clones of vimentin to the diagnosis of salivary
      gland tumors.
AB  - With the evolution of IHC techniques, a broad range of antibodies have become
      available to diagnostic immunohistology. The authors observed different
      expressions of vimentin in salivary gland tumors using two clones of this
      antibody. This study was undertaken to show these differences comparing the
      immunoexpression of two clones of vimentin (V9 and Vim 3B4, DAKO, Carpenteria,
      CA) using 10 pleomorphic adenomas, 10 adenoid cystic carcinomas, and 4
      epithelial/myoepithelial carcinomas of the salivary glands. The V9 clone of
      vimentin was much more efficient in demonstrating the myoepithelial cells in the
      different tumors studied. The Vim 3B4 clone was capable of detecting some
      myoepithelial cells, the plasmacytoid or modified myoepithelial cells in the
      pleomorphic adenoma, but was very weak in epithelial/-myoepithelial carcinomas.
      The difference between the two clones studied is a warning that pathologists need
      to know the specificity and sensitivity of the reagent they are using.

PMID- 16785794
TI  - Tumor cell nuclei extraction from paraffin-embedded lymphoid tissue for
      fluorescence in situ hybridization.
AB  - In this study the authors evaluated a technique for isolating intact tumor nuclei
      from paraffin-embedded lymphoma samples before performing FISH testing to detect
      the lymphoma-specific trans-location t(11;14) that defines mantle cell lymphoma.
      Well-characterized surgical pathology cases of mantle cell lymphoma were
      identified from pathology archives. Thin sections were cut from the paraffin
      embedded tissue blocks. One section was stained using hematoxylin and eosin and
      an area composed exclusively of malignant cells was identified and marked on the
      slide. The corresponding area of the tissue block corresponding to this region
      underwent needle core biopsy, and the tissue was processed to isolate tumor cell
      nuclei and deposited onto a glass slide. The paired sample preparations underwent
      routine FISH testing for detection of the t(11;14)(q13;q32) chromosomal trans
      location. DNA probe hybridization quality was compared between the tissue and
      isolated nuclei. Individual tumor cell nuclei were successfully extracted from
      each of the tissue blocks. The t(11;14) trans-location was detected by FISH in
      all of the samples diagnosed as mantle cell lymphoma. The hybridization signals
      found in the nuclei of extracted tumor cells were bright, planar, and easily
      identified. Detection of signal was superior to that on whole tissue samples,
      where signals often overlapped or were truncated. This technique produces intact
      nuclei for analysis, preserves the tissue block for additional studies, and
      allows sampling of a specific area of the tissue block. This approach may be
      particularly useful when the amount of diagnostic tissue is limited.

PMID- 16785795
TI  - Multiparameter immunofluorescence on paraffin-embedded tissue sections.
AB  - Immunohistochemical techniques have gained increasing importance in diagnostics
      and research. While formalin-fixed, paraffin-embedded human tissue retains
      excellent morphology, the detection of antigens by immunofluorescence in its
      sections and especially the demonstration of multiple simultaneous antibodies
      have limitations. Double immunofluorescence labeling of routinely processed
      paraffin sections has been described previously. The signal intensity observed
      after triple labeling has been reported to be significantly inferior to that
      obtained by application of double fluorochromes. The authors show multicolor
      labeling of three and four primary antibodies in routinely processed paraffin
      embedded tissue sections using a standardized immunofluorescence technique. In
      addition, procedures to reduce background staining and to avoid nonspecific
      double staining are described.

PMID- 16785796
TI  - Development of new rabbit monoclonal antibody to progesterone receptor (Clone
      SP2): no heat pretreatment but effective for paraffin section
      immunohistochemistry.
AB  - Evaluation of estrogen and progesterone receptor (ER, PgR) status in breast
      cancer is widely used for the prediction of the response to endocrine therapy and
      as a biologic parameter closely related to disease prognosis. The IHC method is
      considered to be a specific, sensitive, and economical method for determining ER
      and PgR status. The authors developed the first rabbit anti-PgR mAb (clone SP2)
      used in IHC on formalin-fixed, paraffin-embedded tissue sections from breast
      carcinomas. This new antibody, compared with currently available anti-PgR
      antibodies, has important advantages, including its reactivity even without heat
      based antigen retrieval of fixed-embedded tissue sections in IHC and the
      predominance of nuclear immunostaining with only very low cytoplasmic signal. A
      comparative study of IHC on 107 histologic specimens from breast cancer cases
      showed that SP2 yields the same results as the wellknown mouse mAb to PgR (clone
      1A6). The antibody affinity of SP2 is 12 times higher than that of 1A6. Thus, SP2
      may prove of great value in the assessment of PgR status in human breast cancer.

PMID- 16785797
TI  - Morphologic, immunologic, and molecular methods to detect bacillus anthracis in
      formalin-fixed tissues.
AB  - Due to the importance of Bacillus anthracis as a cause of naturally occurring
      infection among humans and as an agent of bioterrorism, there is a vital need for
      rapid and specific assays, including immunohistochemistry (IHC) and polymerase
      chain reaction (PCR) assays, to detect the bacterium in formalin-fixed tissues.
      Colorimetric IHC assays were developed using a multistep indirect immunoalkaline
      phosphatase method with anti-B. anthracis cell wall (EAII-6G6-2-3) and anti-B.
      anthracis capsule (FDF-1B9) mAbs to detect B. anthracis antigens in formalin
      fixed, paraffin-embedded bacterial cultures and tissues. B. anthracis antigens
      were localized, using both antibodies, in samples from B. anthracis-infected
      animals and humans. The colorimetric IHC assay with both antibodies was expedient
      in diagnosing the presence of B. anthracis in formalin-fixed, paraffin-embedded
      tissue from bioterrorism-associated cases of inhalational and cutaneous anthrax
      and from a case of naturally occurring cutaneous anthrax. Using the same
      antibodies, confocal microscopy demonstrated the structure of replicating B.
      anthracis in tissues. B. anthracis-specific primers were successfully used with
      PCR to amplify and detect B. anthracis sequences derived from formalin-fixed
      tissues of anthrax cases. In this study, morphologic, immunologic, and molecular
      assays were used to study and diagnose 22 veterinary and human anthrax cases.

PMID- 16785798
TI  - Perinuclear dot-like cytokeratin 20 staining in small cell neuroendocrine
      carcinoma of the ovary (pulmonary-type).
AB  - Primary ovarian small cell carcinomas are rare tumors that are subclassified into
      the hypercalcemic (HT) and the pulmonary type (PT), and each tumor type has
      different clinicopathologic characteristics. However, overlapping morphologic
      features can make the distinction between these lesions difficult. The PT small
      cell carcinoma is very rare, with only one series and a few case reports
      published. The authors report two additional cases of this entity and also report
      for the first time the immunohistochemical finding of perinuclear dot-like
      staining with cytokeratin 20. This staining pattern has been reported only for
      Merkel cell carcinoma and salivary gland small cell carcinoma. The authors
      suggest that the punctate CK20 staining is a useful tool in the diagnostic
      distinction of PT small cell carcinoma from HT small cell carcinoma, from other
      primary ovarian tumors such as granulosa cell tumors, and from metastatic
      neuroendocrine tumors originating at primary sites such as the lung. Since the
      authors' conclusions are based on two cases of this rare entity, additional cases
      will need to be studied in the future.

PMID- 16785799
TI  - CDX2 expression and lung cancer.

PMID- 16785800
TI  - Combined C-11 methionine and F-18 FDG PET imaging in a case of neurosarcoidosis.
AB  - PURPOSE: PET scanning of the brain with F-18 FDG and C-11 methionine (MET) is
      useful for characterizing brain lesions discovered at MRI or CT. Most positive
      PET scans indicate malignancy. However, this case report demonstrates positive F
      18 FDG and C-11 MET PET scans in a patient with a nonmalignant condition,
      neurosarcoidosis. MATERIALS AND METHODS: We detail the history and evaluation of
      a 59-year-old woman who presented with ataxia. The patient's evaluation included
      a contrast-enhanced MRI followed by PET scanning of the brain with C-11 MET and
      of the brain and trunk with F-18 FDG. The patient subsequently underwent biopsy
      of a lesion as directed by MRI and PET. RESULTS: The MRI demonstrated multiple
      enhancing leptomeningeal lesions consistent with metastatic disease. PET with F
      18 FDG and C-11 MET demonstrated lesions in both cerebellar hemispheres with F-18
      FDG accumulation in the mediastinum and left hilum. Biopsy of a brain lesion
      directed by MRI and PET revealed sarcoidosis. CONCLUSIONS: In evaluating brain
      lesions, PET with F-18 FDG and C-11 MET can help localize the lesion best suited
      for biopsy. However, not all lesions that have increased uptake on C-11 MET or F
      18 FDG PET are malignant. Granulomatous inflammatory diseases such as
      neurosarcoidosis should also be considered in the differential diagnosis.

PMID- 16785801
TI  - Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with
      histopathologic confirmation.
AB  - PURPOSE: The purpose of this study is to determine the value of Tc-99m HMPAO
      SPECT in the diagnosis of the dementias, with particular reference to Alzheimer
      disease. MATERIALS AND METHODS: Tc-99m HMPAO was used with a 3-camera scanner to
      produce 5 sets of sectional images of the brain. Diagnosis was made by a
      physician blinded to the clinical diagnosis. Results in 49 subjects were
      ultimately compared with neuropathologic study of the brain at autopsy. RESULTS:
      Sensitivity = 86.7% (68.4-95.6%, 95% confidence interval [CI]), specificity =
      89.5% (65.5-98.2% CI), positive predictive value = 92.9% (75.0-98.8% CI),
      negative predictive value = 81% (57.4-93.7% CI), accuracy = 87.8% (74.5-94.9%
      CI), likelihood ratio = 8.23% (7.09-9.57% CI). CONCLUSIONS: Comparison is made
      with several other SPECT and PET series with histopathologic correlation. Brain
      blood flow SPECT is useful in the diagnosis and differential diagnosis of the
      dementias.

PMID- 16785802
TI  - Lymphadenopathy resulting from acute hepatitis C infection mimicking metastatic
      breast carcinoma on FDG PET/CT.
AB  - We report a case documenting fluorodeoxyglucose (FDG) accumulation in upper
      abdominal lymph nodes resulting from acute hepatitis C infection. A 42-year-old
      African-American female with a history of metastatic breast carcinoma was found
      to have hypermetabolic porta hepatic, peripancreatic, and paraaortic
      lymphadenopathy and hypermetabolism in the spleen on a surveillance FDG positron
      emission tomography/computed tomography (PET/CT) scan. Concurrently, she was
      diagnosed with acute hepatitis C infection. Antiviral therapy was not recommended
      secondary to the low level of detectable virus at the time of diagnosis. Her
      breast cancer therapy regimen was continued unaltered. FDG PET/CT scan was
      repeated 2 months later as a result of concern that the hypermetabolic lymph
      nodes represented metastatic disease; however, the scan revealed complete
      resolution of the previously abnormal findings. The resolution of the
      lymphadenopathy and the patient's clinical course led to the conclusion that the
      most likely explanation for the FDG PET/CT findings was inflammation secondary to
      acute hepatitis C infection and not metastatic breast carcinoma. Inflammatory and
      infectious processes accumulate FDG, occasionally resulting in false-positives
      for malignancy. Infected macrophages in the lymph nodes draining the liver in
      this case and stimulation of a cellular immune response by the hepatitis C virus,
      with resultant cytokine production by cytotoxic and T-helper cells, offer
      possible explanations for the findings seen on FDG PET/CT in this case. This case
      highlights the importance of clinical history and laboratory correlation for the
      proper interpretation of FDG PET scans.

PMID- 16785804
TI  - F-18 FDG whole-body PET for the assessment of disease activity in patients with
      rheumatoid arthritis.
AB  - PURPOSE OF REPORT: F-18 fluorodeoxyglucose (FDG) positron emission tomography
      (PET) can be used to image synovitis in patients with rheumatoid arthritis (RA).
      The aim of this study was to evaluate if a simple scoring system based on visual
      assessment of FDG joint uptake correlates with the clinical assessment of
      patients with RA undergoing antiinflammatory treatment. MATERIALS AND METHODS:
      Seven patients with active RA underwent whole-body FDG PET and clinical
      assessment before and after treatment with the antitumor necrosis factor alpha
      antibody (infliximab). A PET total joint score, ie, the sum of all scores based
      on FDG uptake intensity between zero and 4 in 28 joints, was correlated with a
      total joint score based on the clinical disease activity in the same joints using
      a Spearman rank correlation. RESULTS: The PET based total joint score was
      similarly high before onset as was the clinical total joint score. The decrease
      of FDG joint uptake in the follow-up PET scans correlated significantly with the
      clinical assessment. Additionally, synovial FDG uptake was found in
      extraarticular sites such as tendon sheaths and bursae. CONCLUSIONS: Visual
      assessment of FDG uptake shows a significant correlation with clinical evaluation
      of disease activity in patients with RA undergoing antiinflammatory treatment.

PMID- 16785803
TI  - Thyroid cancer presenting as a PET incidentaloma in a patient with concomitant
      breast cancer metastases to the thyroid.
AB  - INTRODUCTION: Metastases to the thyroid gland are considered a rare cause of
      thyroid tumor. Furthermore, a relationship between breast and thyroid carcinoma
      has been previously proposed. CASE DESCRIPTION: We describe the case of a 59-year
      old woman who presented with simultaneous papillary and breast carcinoma within
      the thyroid gland. F-18 fluorodeoxyglucose (FDG) positron emission tomography
      (PET) done for the evaluation of her metastatic breast cancer revealed a thyroid
      incidentaloma with a high metabolic rate (standardized uptake value [SUV] of 13).
      She underwent thyroidectomy and the pathology revealed papillary thyroid
      carcinoma corresponding to the lesion visualized on FDG PET. However, small
      metastatic implants of breast carcinoma were seen within the opposite thyroid
      lobe. CONCLUSION: This is a rare description of a concomitant papillary thyroid
      carcinoma presenting as an FDG PET incidentaloma alongside breast cancer
      metastases to the thyroid gland. Thyroid and breast cancer sometimes occur in the
      same patient. However, no explanation has been found to link these 2 cancers.
      Although uncommon, FDG PET thyroid incidentalomas seem to harbor a higher rate of
      malignancy than incidentalomas found on conventional imaging. In the appropriate
      clinical setting, it is therefore suggested to investigate these lesions
      thoroughly.

PMID- 16785805
TI  - False-positive restaging PET scans involving the spleen in two patients with
      aggressive non-Hodgkin lymphoma.
AB  - We report 2 patients with aggressive non-Hodgkin lymphoma who had positive
      restaging PET scans limited to the spleen and no significant uptake in nodal
      areas of previously known disease. Examination of the resected spleens from both
      patients revealed extensive inflammation surrounding necrotic tumor with no
      evidence of viable lymphoma or active infection. It is suggested that close
      observation of such patients for evidence of progressive disease may be
      considered as opposed to immediate intervention.

PMID- 16785807
TI  - Persistent generalized lymphadenopathy (PGL) mimicking lymphoma on whole-body FDG
      PET/CT imaging.

PMID- 16785806
TI  - Use of 2-deoxy-2-[F-18]-fluoro-D-glucose positron emission tomography to monitor
      therapeutic response by rhabdomyosarcoma in children: report of a retrospective
      case study.
AB  - PURPOSE: The purpose of this study was to study the use of 2-deoxy-2-[F-18]
      fluoro-D-glucose positron emission tomography (F-18 FDG PET) for monitoring
      therapeutic response by rhabdomyosarcoma (RMSA) in children. PATIENTS AND
      METHODS: A retrospective case study was performed by searching a computer
      database for the patients with RMSA in whom F-18 FDG PET studies were performed
      pre- and posttreatment. The data of the PET studies from these patients were
      analyzed in conjunction with clinical treatment and other imaging studies to
      determine whether interval changes of F-18 FDG uptake by the RMSA reflect
      response of RMSA to treatment. RESULTS: Four patients with RMSA who received both
      pretreatment and posttreatment F-18 FDG PET studies were identified from the
      database and included in this study. A dramatic decrease of F-18 FDG uptake by
      the tumor was evident in the patients who had a favorable response to the therapy
      and prolonged remission of the disease. In contrast, persistent abnormal FDG
      uptake in one patient was associated with early relapse of the RMSA. CONCLUSIONS:
      F-18 FDG PET may be useful for monitoring therapeutic response by RMSA in
      children, which needs to be verified with a prospective study in a larger patient
      population.

PMID- 16785808
TI  - Follicular hyperplasia: a potential false-positive finding on PET/CT imaging in
      the evaluation of lymphoma.

PMID- 16785809
TI  - Deep venous thrombosis on F-18 FDG PET/CT imaging.

PMID- 16785810
TI  - Esophageal diverticulum presenting as metastatic thyroid mass on iodine-131
      scintigraphy.

PMID- 16785811
TI  - A positional maneuver to augment conventional cholescintigraphy in the evaluation
      of acute acalculous cholecystitis.

PMID- 16785812
TI  - Clearance of unusual muscular uptake of F-18 FDG in the lower lumbar region on a
      repeat FDG-PET scan after oral chlorzoxazone intervention.

PMID- 16785813
TI  - The ischiopubic synchondrosis: changing appearance on PET/CT as a mimic of
      disease.

PMID- 16785814
TI  - Facet joint arthropathy demonstrated on FDG-PET.

PMID- 16785815
TI  - Interesting appearance of osseous hemangioma of the calcaneus on bone
      scintigraphy: correlative imaging with radiography CT and MRI.

PMID- 16785816
TI  - Intense uptake of Tc-99m HMDP in pleural metastasis from osteosarcoma.

PMID- 16785817
TI  - Detection of a stomach gastrointestinal stromal tumor in situs invertus by
      gallium-67 scintigraphy.

PMID- 16785818
TI  - Intense FDG uptake of metastatic clear cell carcinoma from the ovary in a uterine
      leiomyoma.

PMID- 16785819
TI  - F-18 FDG PET-CT appearance of metastatic brachial plexopathy in a case of
      carcinoma of the breast.

PMID- 16785820
TI  - Papillary thyroid cancer with metastasis to the skin.

PMID- 16785821
TI  - F-18 FDG PET in the diagnosis and monitoring of salmonella vertebral
      osteomyelitis: a comparison with MRI.

PMID- 16785822
TI  - Current readings in nuclear medicine.

PMID- 16785823
TI  - The PGH-synthase system and isozyme-selective inhibition.
AB  - Virtually all human cell types can express both cyclooxygenase (COX)-1 and COX-2
      under appropriate circumstances. Both isoforms can subserve physiologic and
      pathophysiologic roles when coupled with the appropriate stimuli and downstream
      prostaglandin (PG)H2-isomerases and prostanoid receptors. Although the ratio of
      maximal biosynthetic capacity of human platelets to the basal rate of production
      of thromboxane A2 is approximately 5000, this ratio is much lower in the case of
      PGI2, thus dictating quite different requirements for the extent and duration of
      COX inhibition in human platelets and vascular endothelial cells to detect
      functional and clinical effects. The development of low-dose aspirin as an
      antiplatelet agent has been instrumental in characterizing the role of platelet
      COX-1 in atherothrombosis. Similarly, though quite unexpectedly, the development
      of coxibs as anti-inflammatory agents has been instrumental in elucidating the
      role of endothelial COX-2 in vascular occlusion. Because of differential
      requirements for the inhibition of thromboxane A2 versus PGI2 biosynthesis in
      vivo, most traditional nonsteroidal anti-inflammatory drugs tend to mimic the
      effects of coxibs, rather than aspirin, on prostanoid-dependent cardiovascular
      homeostasis.

PMID- 16785824
TI  - Cyclooxygenase-2 inhibition and coagulation.
AB  - Selective inhibitors of cyclooxygenase-2 (COX-2) have come under scrutiny because
      of a possibly increased thrombotic risk observed in retrospective studies and
      comparatively small cancer trials. Indeed, inhibition of COX-2 may favor a
      prothrombotic environment by suppressing endothelial prostacyclin synthesis while
      leaving COX-1-dependent platelet thromboxane (TX) A2 synthesis unopposed.
      However, in vitro studies have shown that the effect of coxibs on coagulation is
      dependent on several variables; for example, the coxib celecoxib reduces
      endothelial tissue factor expression, a key initiator of the coagulation cascade.
      Furthermore, animal studies are inconclusive as some studies investigating the
      effect of COX-2 inhibition in atherosclerosis imply a detrimental effect of
      coxibs, whereas others suggest a beneficial effect on plaque progression and
      stability. In healthy human subjects and in patients with atherosclerotic
      vascular diseases, the effect of COX-2 inhibition on coagulation is equally
      unclear as no prospective, randomized, double-blinded studies sufficiently
      powered to investigate cardiovascular endpoints have been performed to directly
      investigate a potentially cardiotoxic effect of coxibs. Here, we review the
      effect of COX-2 inhibition on the coagulation system; we discuss the molecular
      mechanisms involved and summarize important clinical trials in which an increased
      frequency of thrombotic complications coxibs was observed.

PMID- 16785825
TI  - Cyclooxygenase-2 and nitric oxide.
AB  - Nitric oxide (NO) is a simple but pluripotent molecule that is mainly released
      from vascular endothelial cells where it is formed intracellularly by nitric
      oxide synthase from L-arginine in response to several stimuli, including shear
      stress or muscarinic receptor stimulation. NO stimulates guanylyl cyclase to form
      cyclic guanosine monophosphate, which results in relaxation and vasodilatation of
      vascular smooth muscle cells (VSMCs). In addition, NO prevents adhesion and
      aggregation of platelets, and it possesses anti-inflammatory, antiproliferative,
      and antimigratory effects on leukocytes, endothelial cells, and VSMCs, thus
      offering protection from atherosclerosis. Dysfunction of the vascular endothelium
      has been documented in most conditions that promote or are associated with
      atherosclerosis and is characterized by a reduced bioavailability of NO. The
      healthy endothelium prevents adhesion and migration of leukocytes, proliferation
      of VSMCs, and platelet adhesion and aggregation. Maintaining the balance of blood
      flow and thrombus formation is also a major task of the vascular endothelium. It
      has been shown that both NO and prostacyclin, a cyclooxygenase-derived relaxing
      factor, inhibit activation of platelets and regulate vasomotion. Reduced NO and
      prostacyclin levels can result in endothelial dysfunction, which is recognized as
      the first step in the atherogenic process. It is of note that chronic
      inflammation conditions, such as rheumatoid arthritis, are associated with
      endothelial dysfunction. The reduced NO bioavailability may therefore explain the
      increased risk for cardiovascular events in patients with chronic low-grade
      inflammation, such as rheumatoid arthritis and osteoarthritis. Thus, this article
      provides an overview of the impact of inflammation and anti-inflammatory
      treatment with cyclooxygenase inhibitors on endothelial function.

PMID- 16785826
TI  - COX-2 and atherosclerosis.
AB  - Inflammation plays a central role in the development of atherosclerotic disease,
      from the early phases of lesion formation to plaque disruption, the main
      underlying cause of acute ischemic syndromes. Arachidonic acid metabolism is
      implicated in the pathophysiology of ischemic syndromes affecting the coronary or
      cerebrovascular territory, as demonstrated by biochemical measurements of
      eicosanoid biosynthesis and the results of inhibitor trials in these settings. In
      particular, much attention has been focused on the pathway catalyzed by
      cyclooxygenase (COX), which leads to the generation of a variety of lipid
      mediators known as prostanoids. Two COX isozymes have been characterized, COX-1
      and COX-2, that differ in terms of regulatory mechanisms of expression, tissue
      distribution, substrate specificity, and preferential coupling to upstream and
      downstream enzymes. Whereas the role of platelet COX-1 in acute ischemic diseases
      is established, the role of COX-2 in atherothrombosis remains unclear. In this
      article, we summarize the findings from our group suggesting a crucial role for
      COX-2 in modulating atherosclerotic plaque stability or instability, according to
      the variable expression of upstream and downstream enzymes in the prostanoid
      biosynthesis.

PMID- 16785827
TI  - COX-2 and the kidney.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment
      of pain and inflammation. Nonselective NSAIDs inhibit both cyclooxygenase (COX)-1
      and COX-2. Nephrotoxicity of nonselective NSAIDs has been well documented. The
      effects of selective COX-2 inhibitors on renal function and blood pressure are
      attracting increasing attention. In the kidney, COX-2 is constitutively expressed
      and is highly regulated in response to alterations in intravascular volume. COX-2
      metabolites have been implicated in the mediation of renin release, regulation of
      sodium excretion, and maintenance of renal blood flow. Similar to nonselective
      NSAIDs, inhibition of COX-2 may cause edema and modest elevations in blood
      pressure in a minority of subjects. COX-2 inhibitors may also exacerbate
      preexisting hypertension or interfere with other antihypertensive drugs.
      Occasional acute renal failure has also been reported. Caution should be taken
      when COX-2 inhibitors are prescribed, especially in high-risk patients (including
      elderly patients and patients with volume depletion).

PMID- 16785828
TI  - Blood pressure effects of COX-2 inhibitors.
AB  - There has been significant recent interest in the cardiovascular effects of
      cyclooxygenase 2 (COX-2) selective inhibitors. Whereas much attention has been
      focused on the putative prothrombotic effect of these agents, their cardiorenal
      and blood pressure elevating actions may be of equal if not greater importance to
      cardiovascular risk. COX-2 is widely expressed throughout the kidney, and
      inhibition of this enzyme is contributory to reduced glomerular filtration, salt
      and water retention, and blood pressure elevation. The key issues in relation to
      COX-2 inhibitors and blood pressure are whether these blood pressure-elevating
      effects are similar to or differ from nonselective nonsteroid anti-inflammatory
      drugs, whether differences exist among COX-2 inhibitors in regard to blood
      pressure regulation, and if so, possible mechanisms underlying blood pressure
      differences between COX-2 inhibitors. With regard to the last issue, possible
      mechanisms include greater COX-2 selectivity of certain agents such as rofecoxib,
      the differing half-life of these agents, the carbonic anhydrase activity of
      celecoxib (which may offset renal-induced salt and water retention), and possible
      aldosterone modulation by rofecoxib. Finally, and perhaps most important, the
      issue arises as to whether blood pressure elevation may contribute in whole or in
      part to the increase in cardiovascular events observed with these agents in some
      but not all studies. Ultimately, adequately powered, prospective randomized
      clinical trials assessing relevant cardiovascular endpoints are required to
      address many of these outstanding questions. Such studies have recently been
      announced and will commence soon.

PMID- 16785829
TI  - Why and how to use NSAIDs in osteoarthritis.
AB  - There is an increasing body of evidence that an inflammatory process can be
      involved in the development and the progression of osteoarthritis. Such
      inflammation can be observed at both the cartilage, subchondral bone, and
      synovial tissue level. Of the 2 main categories of anti-inflammatory drugs
      [corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs)], NSAIDs are
      the most commonly used oral drugs in osteoarthritis. The symptomatic short-term
      effect of coxibs is similar to the conventional NSAIDs one and of greater
      magnitude than the one of analgesics such as paracetamol (acetaminophen). On the
      basis of current knowledge of potential gastrointestinal and, more importantly,
      cardiovascular side-effects, the still remaining important question is related to
      the efficacy-toxicity balance of a chronic systematic daily intake of NSAIDs
      versus an "at request" (PRN) intake.

PMID- 16785830
TI  - Expectations from patients with rheumatoid arthritis regarding COX-2s: cutting to
      the heart of the matter.
AB  - Before the withdrawal of 2 COX-2 selective agents (COX-2s) from the market, many
      rheumatoid arthritis patients were using these products regularly, with disease
      modifying antirheumatic agents. Clinical trials have shown benefit of COX-2s
      equivalent to nonselective nonsteroidal anti-inflammatory drugs (NS-NSAIDs) in
      rheumatoid arthritis. Better gastrointestinal (GI) safety has been demonstrated
      with COX-2s; numerical but not statistical benefit with concomitant use of
      cardiovascular (CV) doses of aspirin. COX-2 benefit may extend to lower GI blood
      loss against which proton pump inhibitors are not protective. COX-2s are
      associated with hypertension and edema of similar magnitude to NS-NSAIDs in
      predisposed individuals. Epidemiologic studies and clinical trials have confirmed
      the association of serious thromboembolic (CV) events and congestive heart
      failure with rofecoxib>25 mg daily, celecoxib, and NS-NSAIDs, although there is a
      paucity of long-term data. Important questions remain regarding relative GI and
      CV risks: is concomitant aspirin protective when coadministered with COX-2s? Does
      this abrogate their GI benefit? As identified many years ago with NS-NSAIDs,
      patients may respond to one and not another; COX-2s should be considered
      individually and not as a single "class." Patients deserve the opportunity to
      make a choice about the perceived benefit/risk assessment when using these
      therapies, with the collaboration of their physician.

PMID- 16785831
TI  - GI risk and risk factors of NSAIDs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in
      the United States. Ulcers are found at endoscopy in 15% to 30% of patients using
      NSAIDs regularly. The annual incidence of upper gastrointestinal (GI)
      complications such as bleeding with regular NSAID use is approximately 1.0% to
      1.5%, whereas the annual rate of upper GI clinical events (complicated plus
      symptomatic uncomplicated ulcers) is approximately 2.5% to 4.5%. Upper GI
      symptoms such as dyspepsia also occur in many patients taking NSAIDs--at a
      relative risk of about 1.5 to 2 compared with that in patients without NSAID use.
      Important risk factors for upper GI clinical events include older age, prior
      history of upper GI events, use of corticosteroids or anticoagulants, and high
      dose or multiple NSAIDs (including NSAID plus low-dose aspirin). Lower GI
      clinical events such as bleeding may also occur with NSAIDs, although they are
      less common and less well studied than upper GI events. The decision to employ a
      protective strategy to decrease NSAID-associated GI clinical events is based on
      risk stratification. Strategies employed include the use of non-NSAID analgesics,
      use of lowest effective dose of NSAID, use of medical cotherapy (eg, proton pump
      inhibitor, misoprostol), or use of coxibs.

PMID- 16785832
TI  - Nonsteroidal anti-inflammatory drugs versus selective COX-2 inhibitors in the
      upper gastrointestinal tract.
AB  - There are enough basic data supporting the use of coxibs with regard to the upper
      GI tract in patients with the need for continuous treatment of joint pain. The
      clinical studies available clearly show that coxibs induce fewer lesions and
      complications in volunteers and in patients when compared with NSAIDs. However,
      in Helicobacter pylori- positive patients the advantage seems less clear. The
      combination of NSAID plus PPI is not worse with regard to duodenal ulcers and
      recurrent clinical complications and is more cost effective than the use of
      coxibs. Similarly, with the concomitant use of aspirin even in low doses no major
      advantage of coxibs has been demonstrated. The combination of coxibs and PPI in
      high-risk patients needs to be studied. It is unclear at the moment how important
      are the changes in the lower GI tract. Considering the current controversy
      regarding cardiovascular events, there is no major reason to prefer coxibs to
      conventional NSAID plus PPI in patients needing long-term treatment.

PMID- 16785833
TI  - Rofecoxib increases susceptibility of human LDL and membrane lipids to oxidative
      damage: a mechanism of cardiotoxicity.
AB  - Clinical investigations have demonstrated a relationship between the extended use
      of rofecoxib and the increased risk for atherothrombotic events. This has led to
      the removal of rofecoxib from the market and concern over the cardiovascular
      safety of other cyclooxygenase (COX)-2 selective agents. Experimental findings
      from independent laboratories now indicate that the cardiotoxicity of rofecoxib
      may not be a class effect but because of its intrinsic chemical properties.
      Specifically, rofecoxib has been shown to increase the susceptibility of human
      low-density lipoprotein and cellular membrane lipids to oxidative modification, a
      contributing factor to plaque instability and thrombus formation. Independently
      of COX-2 inhibition, rofecoxib also promoted the nonenzymatic formation of
      isoprostanes and reactive aldehydes from biologic lipids. The basis for these
      observations is that rofecoxib alters lipid structure and readily forms a
      reactive maleic anhydride in the presence of oxygen. By contrast, other selective
      (celecoxib, valdecoxib) and nonselective (naproxen, diclofenac) inhibitors did
      not influence rates of low-density lipoprotein and membrane lipid oxidation. We
      have now further confirmed these findings by demonstrating that the prooxidant
      activity of rofecoxib can be blocked by the potent antioxidant astaxanthin in
      homochiral form (all-trans 3S, 3'S). These findings provide a mechanistic
      rationale for differences in cardiovascular risk among COX-selective inhibitors
      because of their intrinsic physicochemical properties.

PMID- 16785834
TI  - NSAIDs, coxibs, and the intestine.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are capable of damaging the whole
      gastrointestinal tract. Small and large intestinal injuries manifest as acute
      changes in permeability with endoscopic erosions, chronic erosions and ulcers,
      diaphragms in the small bowel, and an increase in small and large bowel
      complications including perforation and diverticular bleeding. It is quite
      likely, though not proven, that such lesions contribute to anemia in patients
      taking them. A growing body of data shows that selective inhibitors of the
      cyclooxygenase-2 enzyme have much reduced toxicity in this respect. In addition,
      NSAID use has also been associated with development or relapse of ulcerative
      colitis. Whether the same is true of Crohn's disease, particularly of the small
      bowel, is less clear. An important point is that there are data that suggest that
      paracetamol may also not be devoid of toxicity. This makes use of selective
      cyclooxygenase-2 inhibitors attractive. There have been a number of reports of
      their use in inflammatory bowel disease. However, many of these have principally
      involved Crohn's disease and there have not been enough to be clear whether they
      affect the influence of relapse of ulcerative colitis.

PMID- 16785835
TI  - Coxibs and cancer prevention.
AB  - Preventive medicine is becoming a cornerstone in our concept of health. This is
      especially significant in regard to cancer, as cancer is predicted to become the
      leading cause of death, surpassing heart disease, by the end of this decade. The
      prevention of colorectal cancer (CRC) has become an important public health goal
      because of the high incidence of CRC, with more than 945,000 new cases expected
      worldwide in 2006, and the considerable mortality and morbidity associated, with
      more than 492,000 deaths expected worldwide in the same year. The past 2 decades
      have seen the emergence of chemopreventive agents that have 1 of 3 effects:
      inhibiting, delaying, or reversing carcinogenesis. Notwithstanding a substantial
      body of evidence suggesting an inverse relationship between aspirin or
      nonsteroidal anti-inflammatory drug use and CRC incidence and mortality, the use
      of traditional nonsteroidal anti-inflammatory drugs in the chemoprevention of CRC
      is limited by their gastrointestinal toxicity. The favorable gastrointestinal
      safety profile of selective cyclooxygenase-2 inhibitors has therefore made them
      particularly attractive for this purpose. There has been concern, however, that
      selective cyclooxygenase-2 inhibitors may increase the risk of cardiovascular
      events, possibly by reducing endothelial prostacyclin production while leaving
      platelet thromboxane A2 generation unopposed. In the intriguing jigsaw puzzle of
      cancer prevention, we now have a definite positive answer for the basic question
      "if," but several other parts of the equation (proper patient selection, ultimate
      drug, optimal dosage, and duration) are missing. The most challenging task is to
      find the proper place for these interventions in the entire effort of cancer
      prevention, in subjects at risk for colorectal neoplasia, and in those at risk
      for other tumors. The achievement of this important goal may contribute to the
      conversion of CRC into a truly preventable disease.

PMID- 16785836
TI  - The role of COX-2 inhibitors in the treatment of postoperative pain.
AB  - Postoperative pain requires treatment not only to provide comfort to patients but
      also to improve postoperative outcome. Anti-inflammatory compounds are an
      important component of multimodal analgesia in the postoperative period. The
      newer cyclooxygenase (COX)-2 inhibitors are as effective as classical
      nonsteroidal anti-inflammatory drugs (NSAIDs) in this setting. However, COX-2
      inhibitors offer a number of advantages over NSAIDs when used to treat
      postoperative pain. These include a reduced incidence of gastrointestinal
      ulceration and no inhibitory effect on platelet function and thereby a reduced
      risk of blood loss. Other benefits are less impairment of bone healing and no
      induction of bronchospasm in patients with aspirin-sensitive asthma. Increased
      cardiovascular thromboembolic events by COX-2 inhibitors have been reported after
      coronary artery bypass graft surgery only, but in general, surgery studies the
      incidence of such complications was comparable to placebo. Overall, COX-2
      inhibitors offer a number of advantages over classical NSAIDs in the
      postoperative pain setting, but require the same caution with regard to renal
      effects.

PMID- 16785837
TI  - Cyclooxygenase inhibition: what should we do to resolve the confusion? An
      American perspective.
AB  - Recent placebo-controlled clinical trials suggest excessive adverse
      cardiovascular (CV) events associated with cyclooxygenase (COX)-2 selective
      nonsteroidal anti-inflammatory drugs (NSAIDs), developed to reduce
      gastrointestinal irritation associated with nonselective NSAIDs. Subsequent
      retrospective analyses of observational series and non-CV clinical trials suggest
      that CV events may occur with modest excess with all NSAIDs, nonselective and COX
      2 selective, compared with nonuse of these drugs, may be dose related, and do not
      differ substantially in frequency among various NSAIDs. However, inadequacy of
      study designs, controls, and events has precluded definition of the risk-benefit
      relationship of COX-2 selective and nonselective NSAIDs. Resolution of this
      problem requires several different types of studies, necessarily including
      appropriately designed randomized, controlled trials comparing commonly employed
      nonselective and COX-2 selective NSAIDs in patients expected to benefit (ie,
      those with symptomatically severe arthritis) who also have coronary occlusive
      disease so that achievable noninferiority trial size has power sufficient to
      resolve relatively small differences in adverse CV (and gastrointestinal) event
      rates. This article explores the goals and possible designs of trials appropriate
      for defining risk-benefit relationship that must be known for optimal application
      of NSAID therapy.

PMID- 16785838
TI  - A European's perspective of COX-2 drug safety.
AB  - Regulators require less evidence to take action on drug safety concerns than
      would be required to grant drug efficacy claims. Such an asymmetrical view of
      risk points to the need for large studies to judge the safety of novel medicines
      compared with standard therapy as smaller sample sizes might produce unreliable
      and misleading toxicity signals. Large studies conducted in the classical manner
      are expensive and difficult to conduct. In addition, tight entry criteria and
      strictly protocolized care results in such trials having poor external validity.
      If the safety of medicines is to be judged efficiently, novel, easier to conduct,
      and less-expensive solutions are required. Such trials could have improved
      external validity were they incorporated into normal care. This paper discusses
      the safety of cyclooxygenase-2 inhibitors and describes the sort of studies that
      could be carried out to gather better safety information on their use versus
      standard nonsteroidal anti-inflammatory drugs.

PMID- 16785839
TI  - Cyclo-oxygenase Inhibitors: Aspects in Cardiovascular Medicine, Gastroenterology
      and Rheumatology. Proceedings of the COX-2 Summit, September 7-8, 2005, Zurich,
      Switzerland.

PMID- 16785841
TI  - Pituitary gland: development, normal appearances, and magnetic resonance imaging
      protocols.
AB  - In this article, I will review the normal anatomy of the pituitary gland starting
      with a brief review of aspects of its origin and development that are pertinent
      to radiologists. The anatomy of the anterior and posterior lobes will be
      addressed as will be that of the surrounding structures and of the vascular
      structures of the gland. Radiologists need to be familiar with the normal
      magnetic resonance imaging appearance of the gland and the changes that it
      undergoes throughout life. The normal patterns of contrast enhancement by the
      gland are described. Normal pituitary variations and incidental conditions are
      discussed, and the article finishes by describing appropriate imaging protocols.

PMID- 16785842
TI  - Congenital pathology of the pituitary gland and parasellar region.
AB  - The adenohypophysis and neurohypophysis originate from the combination of 2
      events occurring during the fourth week of life, the development of Rathke pouch
      and of a neuroectodermal evagination of tissue from the floor of the
      diencephalon. Congenital pathology of the pituitary gland and parasellar regions
      derives from abnormalities of these coordinated events. In this article, we
      review the pathogenesis, clinical presentation, and imaging features of common
      and rare congenital disorders of the region of the sella turcica.

PMID- 16785843
TI  - Pituitary adenomas.
AB  - Pituitary adenomas are by far the most common sellar tumor and magnetic resonance
      imaging is the modality of choice for their detection and characterization.
      However, most of these neoplasms are asymptomatic and frequently incidentally
      visualized. One also has to be aware of common other incidental findings and
      normal age-related changes in the appearance of the gland. By convention, 10 mm
      is used as the size threshold to separate macroadenomas from microadenomas. For
      microadenomas, imaging is primarily used for lesion detection and localization,
      whereas with macroadenomas, the goal is to establish whether the mass represents
      a pituitary tumor or some other lesion and to precisely delineate its extent.

PMID- 16785844
TI  - Nonadenomatous tumors of the pituitary and sella turcica.
AB  - While pituitary adenomas make up over 90% of all sellar masses, there are a
      number of less known tumors, both malignant and benign, which may arise within
      the sella turcica. These include relatively common tumors such as meningiomas and
      craniopharyngiomas, as well as extremely rare tumors such as pituitary
      astrocytomas and granular cell tumors. Unfortunately, many of these tumors lack
      characteristic imaging features, often making it extremely difficult to
      distinguish them by imaging alone from the more common pituitary adenoma. In this
      article, we review several nonadenomatous tumors of the sella, with a focus on
      their clinical features and typical MR imaging characteristics.

PMID- 16785845
TI  - Inflammatory and infectious processes involving the pituitary gland.
AB  - Inflammatory and infectious diseases of the pituitary gland are rare, and imaging
      diagnosis may be difficult. They encompass a wide spectrum of pathology including
      autoimmune (lymphocytic) hypophysitis, granulomatous hypophysitis, local
      manifestations of systemic disease, and a multitude of infectious processes.
      Based on extensive review of the literature, this article will present a
      classification scheme, description of pathology, and imaging findings of the
      various inflammatory and infectious entities, along with selected images from our
      case material.

PMID- 16785846
TI  - Parasellar tumors: suprasellar and cavernous sinuses.
AB  - This article will review the presentation and imaging appearance of tumors
      affecting the area around the pituitary gland. For convenience, the lesions will
      be discussed in order of the regions they usually affect. For example, lesions
      affecting the suprasellar region include craniopharyngiomas, optic or
      hypothalamic gliomas, germ cell tumors, epidermoids, dermoids, hamartomas,
      lipomas, and choristomas. Tumors that commonly affect the parasellar cavernous
      sinus include schwannomas and meningiomas. Tumors like chordomas may arise in the
      sphenoid bone or clivus and affect the sella. Metastasis, meningiomas and
      aneurysms may involve any area around the sella. For a detailed discussion of
      normal anatomy and imaging protocols, see the first article of this monograph.

PMID- 16785847
TI  - Postoperative imaging of the pituitary gland.
AB  - Imaging often plays an important role in the management of patients who have been
      surgically treated for pituitary disease. The primary goals of the radiologist
      are to recognize normal postoperative findings, to distinguish iatrogenic changes
      in the sella and surrounding regions from residual tumor, and to detect surgical
      or therapy-related complications when apparent on imaging. Accurate assessment of
      the postoperative pituitary region requires an understanding of the normal sellar
      anatomy and of the common neurosurgical techniques applied to this region and
      familiarity with the appearance of this region in both the acute postoperative
      setting and also upon subsequent subacute and later examinations.

PMID- 16785848
TI  - Abdominal magnetic resonance imaging at 3.0 T: problem or a promise for the
      future?
AB  - The development of transmit-receive body coils and local and phased-array
      radiofrequency receive coils for 3.0-T magnetic resonance imaging (MRI) systems,
      and their recent approval in Europe and North America has promoted a move toward
      higher field, whole-body MRI. With approximately double the signal-noise ratio of
      a 1.5-T system, 3.0-T MR systems can substantially improve image quality and
      image acquisition speed; 3.0 T can potentially deliver square root(2) improvement
      in resolution in the same acquisition time of a comparable study at 1.5 T or one
      half slice thickness with identical coverage or 4-fold speedup in scanning time
      for identical resolution settings. Parallel imaging, multiple coil elements,
      specific absorption rate, and altered MR physical properties at 3.0 T (T1
      relaxation times, susceptibility, T2*) are important issues during optimization
      of sequences at high field. Possible future applications in the abdomen include
      high-resolution, contrast-enhanced imaging of the liver and pancreas; MR
      angiography; and MR spectroscopy. In this article, we will present our initial
      experience with optimization of sequences for abdominal MRI at 3.0 T and will
      include a short description of parallel imaging because of its importance for
      imaging at 3.0 T, general remarks comparing some of the physical properties of
      1.5 T and 3.0 T, and some of the challenges during sequence optimization for the
      abdomen at 3.0 T with examples of abdominal MRI at 3.0 T with 4- and 8-channel
      coils.

PMID- 16785849
TI  - Adult immunization.

PMID- 16785850
TI  - Transdermal methylphenidate (Daytrana) for ADHD.

PMID- 16785851
TI  - Conivaptan (Vaprisol) for hyponatremia.

PMID- 16785852
TI  - Circadian variation of mouse aqueous humor protein.
AB  - PURPOSE: The first aim was to document the 24 h pattern of total protein
      concentration in aqueous humor of the C57BL/6J mouse strain under various
      environmental light-dark conditions. The second aim was to determine the
      diurnal/nocturnal change of aqueous humor protein concentration in the CBA/CaJ
      mouse strain reported to show a unique absence of diurnal/nocturnal elevation of
      intraocular pressure (IOP). METHODS: Mice of both strains were entrained to a
      daily 12 h diurnal/light (6 AM to 6 PM) and 12 h nocturnal/dark cycle. Total
      protein concentrations of aqueous humor were determined using specimens collected
      from C57BL/6J mice every 4 h under standard light-dark, acute constant dark, and
      acute constant light conditions. Aqueous humor protein concentrations in CBA/CaJ
      mice were determined at three diurnal times and three nocturnal times. RESULTS:
      The C57BL/6J mouse strain showed a higher aqueous humor protein concentration
      during the diurnal period than during the nocturnal period under standard light
      dark conditions. This pattern persisted under acute constant dark and was
      modulated under acute constant light. The CBA/CaJ mouse strain showed a similar
      diurnal/nocturnal decrease of total aqueous humor protein concentration.
      CONCLUSIONS: Endogenous circadian variation of aqueous humor protein
      concentration occurs in the C57BL/6J mouse strain. The nocturnal concentration is
      significantly lower than the diurnal concentration. A similar diurnal/nocturnal
      decrease of aqueous humor protein concentration occurs in the CBA/CaJ mouse
      strain, indicating that this change of aqueous humor protein is unrelated to the
      diurnal/nocturnal pattern of IOP.

PMID- 16785853
TI  - Novel mutations of the PAX6 gene identified in Chinese patients with aniridia.
AB  - PURPOSE: Mutations in PAX6 are the major cause of aniridia. Only a few PAX6
      mutations in Chinese have been reported. This study is to identify novel
      mutations in PAX6 of Chinese patients with aniridia. METHODS: Aniridia patients
      were collected from 11 Chinese families, and genomic DNA was prepared from venous
      leukocytes. The coding regions of PAX6 were analyzed by direct sequencing of PCR
      products. Variations detected were further evaluated in available family members
      as well as in controls by using heteroduplex-SSCP analysis. RESULTS: Four novel
      mutations including c.141+1G>A, c.184-3C>G, c.542C>A (Ser181X), and c.562C>T
      (Gln188X) and one known mutation c.120C>A (Cys40X) were identified in PAX6 of
      five unrelated patients with aniridia. All five mutations are expected to
      generate null alleles of PAX6. Varied ocular phenotypes were observed in
      different patients within families. CONCLUSIONS: We identified four novel
      mutations and 1 known mutation in the human PAX6 gene. These results expand the
      mutation spectrum in PAX6 and enrich our knowledge of genotype-phenotype relation
      due to PAX6 mutations.

PMID- 16785854
TI  - Evaluation of the association between OPA1 polymorphisms and primary open-angle
      glaucoma in Barbados families.
AB  - PURPOSE: To investigate whether single nucleotide polymorphisms (SNPs) in the
      OPA1 gene are associated with two primary open-angle glaucoma (POAG) subgroups:
      those with elevated intraocular pressure (POAG/IOP) and those with normal tension
      glaucoma (NTG) in the African-Caribbean population of Barbados, West Indies.
      METHODS: SNPs at intervening sequence (IVS) 8, +4, and +32 of the OPA1 gene were
      directly sequenced from 48 individuals with POAG/IOP, 48 nonglaucomatous
      controls, and 61 people with NTG. The remaining exons of OPA1 were screened for
      sequence variations in the same 48 POAG/IOP participants and 48 controls by
      denaturing high performance liquid chromatography (dHPLC), and identified
      variations were confirmed by bidirectional sequencing. Genotype and allele
      frequencies of all SNPs were compared for statistically significant differences
      using the chi2 and Fisher's exact test. Haplotypes and compound genotypes were
      also analyzed to evaluate the combined effect of the two IVS8 SNPs. RESULTS: The
      analyses of the genotype and haplotype frequencies of IVS8 +4 and +32 do not show
      statistically significant differences between those with POAG/IOP or NTG and
      controls. At IVS8 +32, although there are suggestions of possible associations of
      the CC genotype with NTG (chi2 = 3.81, p = 0.05), and the TC genotype with
      POAG/IOP (chi2 = 4.23, p = 0.04), these differences do not reach statistical
      significance at the level of 0.017 after a Bonferroni correction. In addition,
      the combined genotype comparisons at IVS8 +32 do not support the association (for
      controls compared to NTG chi2 = 4.19, p = 0.12, df = 2; and for controls compared
      to POAG chi2 = 4.83, p = 0.09, df = 2). Sixteen variants are observed in the OPA1
      gene, of which 10 are novel. Neither genotype nor allele frequencies of any SNP
      are found to be associated with POAG/IOP. CONCLUSIONS: Although some results are
      suggestive, there is not sufficient evidence to support an association of the
      SNPs evaluated in OPA1 with POAG/IOP or NTG in the African-Caribbean population
      of Barbados, West Indies.

PMID- 16785855
TI  - Proteomic analysis of opsins and thyroid hormone-induced retinal development
      using isotope-coded affinity tags (ICAT) and mass spectrometry.
AB  - PURPOSE: Analyses that reveal the relative abundance of proteins are informative
      in elucidating mechanisms of retinal development and disease progression.
      However, popular high-throughput proteomic methods do not reliably detect opsin
      protein abundance, which serve as markers of photoreceptor differentiation. We
      utilized thyroid-hormone (TH) treatment of rainbow trout (Oncorhynchus mykiss) as
      a model of cone apoptosis and cone regeneration. We used this model to
      investigate if emerging proteomic technology allows effective analysis of retinal
      development and opsin protein abundance. We also sought to begin a
      characterization of proteomic changes in the retina occurring with TH treatment
      and address whether TH affects proliferation or photoreceptor differentiation.
      METHODS: Retinal homogenates were prepared from control and TH-treated fish.
      Peptides from control and treated homogenates were differentially labeled, using
      isotope-code affinity tags (ICAT) and analyzed using capillary liquid
      chromatography-electrospray ionization-tandem mass spectrometry (capLC-ESI
      MS/MS). This method identifies proteins and quantifies their relative abundance
      between two samples. RESULTS: The relative abundance of many retinal proteins
      changed during TH treatment. These included proteins from every functional class.
      We detected 1,684 different peptides, and our quantification suggests that 94
      increased and 146 decreased in abundance more than 50% during TH treatment. Cell
      cycle proteins appear to be increased, consistent with TH-inducing cell
      proliferation, similar to its effect in Xenopus. Other proteins associated with
      retinal development, such as deltaA and tubulins, changed in abundance during TH
      treatment. Rod opsin and three cone opsins were identified and the relative
      abundance of each changed with TH treatment. CONCLUSIONS: ICAT and capLC-ESI
      MS/MS are an effective complement to other molecular approaches that investigate
      the mechanisms of retinal development. Unlike other proteomic techniques, this
      approach does not require development of species- or tissue-specific methodology,
      such as characterizing two dimensional (2D) gels or antibodies, in order to be
      practical as a high-throughput approach. Importantly, this technology was able to
      assess the relative abundance of opsin proteins. These findings represent the
      first high-throughput proteomic analysis of the retina and demonstrate the
      technique's ability to provide useful information in retinal development.

PMID- 16785856
TI  - Polymorphism of beta-adrenergic receptors and susceptibility to open-angle
      glaucoma.
AB  - PURPOSE: The human trabecular meshwork and ciliary body, which express beta
      adrenergic receptors (ADRB1 and ADRB2), control aqueous humor dynamics. We
      investigated associations of ADRB polymorphisms with open-angle glaucoma (OAG),
      because ADRB gene polymorphisms alter receptor function. METHODS: We studied 240
      Japanese controls and 505 Japanese OAG patients including 211 with primary open
      angle glaucoma (POAG), and 294 with normal-tension glaucoma (NTG). Associations
      of four polymorphisms (Ser49Gly and Arg389Gly in the ADRB1 gene; Arg16Gly and
      Gln27Glu in the ADRB2 gene) were compared between patients and controls. Age,
      intraocular pressure (IOP), and visual field defects at diagnosis were examined
      for associations with polymorphisms. RESULTS: The Arg389Gly polymorphism in the
      ADRB1 gene showed significantly different allele and genotype frequencies in
      patients with NTG than in controls (p = 0.004 and 0.006, respectively). Other
      polymorphisms did not show a significant frequency difference. In POAG patients,
      carriers of Gly16 in the ADRB2 gene were significantly younger at diagnosis than
      noncarriers (p<0.001). The IOP at diagnosis was significantly higher in OAG
      patients carrying 27Glu in the ADRB2 gene than in patients without this allele
      (p<0.001). Clinical characteristics of OAG patients did not differ significantly
      in relation to other polymorphisms. CONCLUSIONS: Certain polymorphisms of the
      ADRB1 and ADRB2 genes influence the pathophysiology of OAG in Japanese patients.

PMID- 16785862
TI  - Molluscum contagiosum infection after reduced-intensity cord blood
      transplantation.

PMID- 16785863
TI  - Split chimerism may be enough to cure Evans syndrome.

PMID- 16785864
TI  - Risk factors and characteristics of ocular complications, and efficacy of
      autologous serum tears after haematopoietic progenitor cell transplantation.
AB  - The objective of the study was to evaluate the frequency and clinical
      characteristics of ocular complications and their risk factors, as well as
      autologous serum tears (AST) for the treatment of dry eye in these patients. Data
      from the files of 124 patients who had undergone allogeneic haematopoietic
      progenitor cell transplantation (HPCT) were evaluated. In addition, 33 HPCT
      patients were examined and their data were compared with controls. Analysis of
      tears and AST was performed. Dry eye manifestation occurred in 32% of patients
      and was positively correlated with age over 27 years (P = 0.05), peripheral blood
      progenitor cell transplant (P = 0.002), chronic graft-versus-host disease (P =
      0.0027), and chronic or acute myeloid leukaemia (P = 0.001). Dry mouth and
      Schirmer test < 5 mm were predictive factors for dry eye in HPCT patients (P =
      0.002 and odds ratio 3.9 and P = 0.007, odds ratio = 5.9, respectively).
      Microbiological analysis revealed that six of 11 AST samples were contaminated
      after 30 days of use. The present study supports the role of potential risk
      factors for ocular complications and key elements to detect alterations in the
      tear film from HPCT patients. In addition, AST contamination must be considered
      after longer periods of use.

PMID- 16785865
TI  - Retroviral vector insertions in T-lymphocytes used for suicide gene therapy occur
      in gene groups with specific molecular functions.
AB  - Graft-versus-host disease (GvHD) is a severe complication in the context of
      allogeneic stem cell transplantation and adoptive immunotherapy. The transfer of
      a suicide gene into donor T-lymphocytes (TLCs) allows selective elimination of
      GvHD-causing cells. As retroviral gene transfer into hematopoietic stem cells can
      induce leukaemia, there is an urgent need also to analyze retroviral integration
      sites in TLCs. We examined suicide gene-transduced TLCs in four grafts and from
      four transplanted patients. One-hundred and fifteen integration sites were
      detected in vitro. Of these 90 could be mapped to the human genome; 50% (45) were
      located in genes and 32% (29) were detected 10 kb upstream or downstream of
      transcription start sites. We found a significant overrepresentation of genes
      encoding for proteins with receptor activity, signal transducer activity,
      transcription regulator activity, nucleic acid binding activity and translation
      regulator activity. Similar data were obtained from patient samples. Our results
      point to preferred vector integration patterns, which are specific for the target
      cell population and probably independent of selection processes. Thus, future
      preclinical analysis of the integration repertoire with abundant amounts of
      transduced cells could allow a prediction also for the in vivo situation, where
      target cells are scarce.

PMID- 16785866
TI  - Early engraftment kinetics of two units cord blood transplantation.
AB  - Cord blood transplantation (CBT) is a promising alternative means of allogeneic
      stem cell transplantation. However, limited cell doses may compromise outcome. To
      enhance engraftment, CBT has been conducted using two units with promising
      results. However, little is known about the mechanism of engraftment. Here, we
      analyzed the early engraftment kinetics of eight patients given two unit
      umbilical CBT. Early engraftment kinetics revealed dominancy of one of two units
      from the day of engraftment (absolute neutrophil count > 0.5 x 10(9)/l). The
      median value of percentage of the predominant unit by chimerism analysis at the
      time of engraftment was 88% (60-100%). Two units CBT was found to be a safe,
      effective and promising alternative treatment option with good engraftment
      potential. Dominancy occurred early after CBT and is probably influenced by
      multiple factors.

PMID- 16785867
TI  - Use of intravenous mycophenolate mofetil for graft-versus-host disease
      prophylaxis in an allogeneic hematopoietic stem cell transplant recipient with an
      allergic reaction to cyclosporine and tacrolimus.

PMID- 16785868
TI  - What is the clinical significance of infusing hematopoietic cell grafts
      contaminated with bacteria?
AB  - Although hematopoietic stem cell (HSC) products are routinely cultured for
      sterility, bacterial contamination of these products is rarely observed and
      little is known about the clinical consequences of infusing contaminated grafts.
      We retrieved the sterility cultures of bone marrow and peripheral HSC grafts from
      938 patients transplanted at our center from January 1990 to July 2005. Fever,
      septicemia and other adverse events were assessed for up to 14 days following
      infusion of the graft. Out of the 1502 grafts collected during this 15-year
      period, 15 (1.0%) had a positive sterility culture (11 Gram-positive cocci, 2
      Gram-positive bacilli and 2 Gram-negative bacilli). No correlation was observed
      between the graft contamination rate and the extent of graft manipulation or the
      patient's underlying condition. Thirteen recipients were transplanted with
      contaminated grafts. Five patients were treated with specific pre-emptive
      antibiotics. Only one episode of Staphylococcus epidermidis bacteremia possibly
      related to a contaminated graft was observed on day +5. As the infusion of
      contaminated grafts with Gram-positive skin contaminants rarely results in
      unfavorable clinical outcomes, close patient monitoring without the use of
      specific pre-emptive antibiotics could be appropriate and could avoid antibiotic
      associated adverse events.

PMID- 16785869
TI  - Do negative or positive emotions differentially impact mortality after adult stem
      cell transplant?
AB  - Multiple diverse biomedical variables have been shown to affect outcome after
      hematopoietic stem cell transplantation (HSCT). Whether psychosocial variables
      should be added to the list is controversial. Some empirical reports have fueled
      skepticism about the relationship between behavioral variables and HSCT survival.
      Most of these reports have methodological shortcomings. Their samples were small
      in size and included heterogeneous patient populations with different malignant
      disease and disease stages. Most data analyses did not control adequately for
      biomedical factors using multivariate analyses. The pre-transplant evaluations
      differed from study to study, making cross-study generalizations difficult.
      Nevertheless, a few recently published studies challenge this skepticism, and
      provide evidence for deleterious effects of depressive symptomatology on HSCT
      outcome. This mini review integrates the new data with previously reviewed data,
      focusing on the differential impact of negative and positive emotional profiles
      on survival. Pre-transplant negative emotional profiles are associated with worse
      survival in the long term, whereas pre-transplant optimism about transplant
      appears to affect survival in the short term. These data have practical
      implications for transplant teams. Pre-transplant psychological evaluation should
      assess for specific adverse behavioral risk factors, particularly higher levels
      of depression and lower levels of optimistic expectations about transplant.
      Transplant centers should develop collaborative studies to further test the
      effects of these adverse behavioral risk factors, and run multicenter hypothesis
      driven clinical trials of psychological intervention protocols. Such studies
      should aim to better define pragmatics of assessment and intervention (timing,
      assessment tools, personnel), and evaluate their contribution to improving
      outcome after transplant.

PMID- 16785879
TI  - Assessing research quality.

PMID- 16785881
TI  - Interpreting flow cytometry data: a guide for the perplexed.

PMID- 16785880
TI  - TOLLing away in Brazil.

PMID- 16785882
TI  - Gene expression microarrays: glimpses of the immunological genome.
AB  - Successful microarray experimentation can generate enormous amounts of data,
      potentially very rich but also very unwieldy. Bold outlooks and new methods for
      data analysis and presentation should yield additional insight into the
      complexities of the immune system.

PMID- 16785884
TI  - Division of labor and cooperation between dendritic cells.

PMID- 16785883
TI  - Pursuing gene regulation 'logic' via RNA interference and chromatin
      immunoprecipitation.
AB  - RNA interference and chromatin immunoprecipitation are now firmly established as
      useful methods for studying mechanisms of gene regulation in vivo. Their combined
      use can help elucidate gene regulation 'logic' by aiding in target gene
      identification for transcription factors and chromatin-modifying complexes.

PMID- 16785885
TI  - Supplying the demand for granulocytes.

PMID- 16785886
TI  - NK cell development: gas matters.

PMID- 16785887
TI  - IRF4 - a factor for class switching and antibody secretion.

PMID- 16785889
TI  - Thymic stromal lymphopoietin in normal and pathogenic T cell development and
      function.
AB  - Thymic stromal lymphopoietin, a four helix-bundle cytokine, is expressed mainly
      by barrier epithelial cells and is a potent activator of several cell types,
      particularly myeloid dendritic cells. TSLP influences the outcome of interactions
      between dendritic cells and CD4+ thymocytes and T cells in many situations, such
      as the regulation of the positive selection of regulatory T cells, maintenance of
      peripheral CD4+ T cell homeostasis and induction of CD4+ T cell-mediated allergic
      inflammation.

PMID- 16785986
TI  - TRAIL resistance results in cancer progression: a TRAIL to perdition?
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL, APO-2L) is
      a mediator of cell death that preferentially targets cancer cells. The potential
      of TRAIL as a chemotherapeutic agent is limited, however, because of the
      emergence of TRAIL resistance. Furthermore, recent studies have demonstrated that
      alternative TRAIL signaling is unmasked in TRAIL resistant cells. In these cells,
      the predominant effect of TRAIL receptor activation is the activation of nuclear
      factor-kappaB (NF-kappaB), which promotes tumor metastases and invasion. TRAIL
      resistance can occur at the level of the death inducing signaling complex via
      upregulation of cFLIP or via an increase in antiapoptotic proteins of the Bcl-2
      family. A paradigm emerges from this information, that chemotherapy, targeting NF
      kappaB, cFLIP, or antiapoptotic proteins of the Bcl-2 family, in combination with
      TRAIL maybe more rational than TRAIL therapy alone.

PMID- 16785987
TI  - Fusion tyrosine kinases: a result and cause of genomic instability.
AB  - Reciprocal chromosomal translocations may arise as a result of unfaithful repair
      of spontaneous DNA double-strand breaks, most probably induced by oxidative
      stress, radiation, genotoxic chemicals and/or replication stress. Genes encoding
      tyrosine kinases are targeted by these mechanisms resulting in the generation of
      chimera genes encoding fusion tyrosine kinases (FTKs). FTKs display transforming
      activity owing to their constitutive kinase activity causing deregulated
      proliferation, apoptosis, differentiation and adhesion. Moreover, FTKs are able
      to facilitate DNA repair, prolong activation of G(2)/M and S cell cycle
      checkpoints, and elevate expression of antiapoptotic protein Bcl-X(L), making
      malignant cells less responsive to antitumor treatment. FTKs may also stimulate
      the generation of reactive oxygen species and enhance spontaneous DNA damage in
      tumor cells. Unfortunately, FTKs compromise the fidelity of DNA repair
      mechanisms, which contribute to the accumulation of additional genetic
      abnormalities leading to the resistance to inhibitors such as imatinib mesylate
      and malignant progression of the disease.

PMID- 16785988
TI  - Phospho-regulation of human protein kinase Aurora-A: analysis using anti-phospho
      Thr288 monoclonal antibodies.
AB  - Mammalian Aurora-A is related to a serine/threonine protein kinase that was
      originally identified by its close homology with Saccharomyces cerevisiae Ipl1p
      and Drosophila melanogaster aurora that are key regulators in the orchestration
      of mitotic events. The protein level of Aurora-A, its peak kinase activity during
      mitosis, and its activation have been attributed to phosphorylation. Here we show
      that this enzyme is an arginine-directed kinase and define its substrate
      specificity. We also found that Thr288 within the activation loop is a critical
      residue for activating phosphorylation events in vitro and that it is
      spatiotemporally restricted to a brief window at mitosis on duplicated
      centrosomes and on spindle microtubules proximal to the poles in vivo.
      Immunodepletion assays indicated that an upstream kinase(s) of Aurora-A might
      exist in mammalian cells in addition to autophosphorylation. Furthermore, human
      activated Aurora-A forms complexes with the negative regulator protein
      serine/threonine phosphatase type 1 (PP1) that was negatively phosphorylated on
      Thr320. Interestingly, phospho-specific Aurora-A monoclonal antibodies restrain
      Aurora-A kinase activity in vitro, providing further therapeutic avenues to
      explore.

PMID- 16785989
TI  - Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma
      development in adult mice.
AB  - Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras
      and p53. To investigate their possible involvement in the tumorigenesis, we
      generated a knock-in mouse line with oncogenic K-ras, conditionally expressed by
      Cre/LoxP system on a background of p53 alteration. Electroporation of Cre
      expression vector in skeletal muscle tissues resulted in the generation of tumor
      in adults with tumor incidences of 100% at 10 weeks and 40% at 15 weeks, in p53(
      /-) and p53(-/+) backgrounds, respectively. The tumor histology was pleomorphic
      RMS with characteristic bizarre giant cells, positive for desmin and alpha
      sarcomeric actin and exhibiting remarkable increase in total and phosphorylated
      extracellular signal-regulated protein kinase (ERK)1 and ERK2. Loss of the wild
      type p53 was detected in K-rasG12V-expressed tumors of p53(-/+) mice. Early
      lesions 3 weeks after electroporation consisted of proliferating populations of
      myogenic progenitors, including stem cells positive for ScaI antigen, immature
      cells positive for desmin and neural cell adhesion molecule-positive myotubes.
      Thus, cooperation of oncogenic K-ras and p53 deficiency resulted in the
      development of pleomorphic RMS in adult mice, providing a useful mouse model for
      further detailed studies.

PMID- 16785990
TI  - AHNP-streptavidin: a tetrameric bacterially produced antibody surrogate fusion
      protein against p185her2/neu.
AB  - The anti-p185(her2/neu) peptidomimetic (AHNP) is a small exo-cyclic peptide
      derived from the anti-p185(her2/neu) rhumAb 4D5 (h4D5). AHNP mimics many but not
      all of the antitumor characteristics exhibited by h4D5. However, the
      pharmacokinetic profiles of AHNP are less than optimal for therapeutic or
      diagnostic purposes. To improve the binding affinity to p185(her2/neu) and the
      antitumor efficacy, we have engineered a fusion protein containing AHNP and a
      nonimmunoglobulin protein scaffold, streptavidin (SA). The recombinant protein,
      AHNP-SA (ASA) bound to p185(her2/neu) with high affinity, inhibited the
      proliferation of p185(her2/neu)-overexpressing cells, and reduced tumor growth
      induced by p185(her2/neu)-transformed cells. These data suggest that the
      bacterially produced tetrameric ASA can be used as an antibody-surrogate
      molecule. This class of molecule will play a role in the diagnosis and treatment
      of p185(her2/neu)-related tumors. Our studies establish a general principle by
      which a small biologically active synthetic exo-cyclic peptide can be engineered
      to enhance functional aspects by structured oligomerization and can be produced
      recombinantly using bacterial expression.

PMID- 16785991
TI  - Prolactin modulates phosphorylation, signaling and trafficking of epidermal
      growth factor receptor in human T47D breast cancer cells.
AB  - Prolactin (PRL) is a polypeptide hormone produced by the anterior pituitary gland
      and other sites that acts both systemically and locally to cause lactation and
      other biological effects by interacting with the PRL receptor, a Janus kinase
      (JAK)2-coupled cytokine receptor family member, and activating downstream signal
      pathways. Recent evidence suggests PRL is a player in the pathogenesis and
      progression of breast cancer. Epidermal growth factor (EGF) also has effects on
      breast tissue, working through its receptors, epidermal growth factor receptor
      (EGFR) and ErbB-2 (c-neu, HER2), both intrinsic tyrosine kinase growth factor
      receptors. EGFR promotes pubertal breast ductal morphogenesis in mice, and both
      EGFR and ErbB-2 are relevant in pathogenesis and behavior of breast and other
      human cancers. Previous studies showed that PRL and EGF synergize to enhance
      motility in the human breast cancer cell line, T47D. In this study, we explored
      crosstalk between the PRL and EGF signaling pathways in T47D cells, with an
      ultimate aim of understanding how these two important factors might work together
      in vivo to affect breast cancer behavior. Both PRL and EGF caused robust
      signaling in T47D cells; PRL acutely activated JAK2, signal transducer and
      activator of transcription-5 (STAT5), and extracellular signal-regulated kinase-1
      and -2 (ERK1 and ERK2), whereas EGF caused EGFR activation and consequent src
      homology collagen (SHC) activation and ERK activation. Notably, PRL also caused
      phosphorylation of the EGFR and ErbB-2 at sites detected by PTP101, an antibody
      that recognizes threonine phosphorylation at consensus motifs for ERK-induced
      phosphorylation. PRL-induced PTP101-reactive phosphorylation was prevented by
      pretreatment with PD98059, an ERK pathway inhibitor. Furthermore, PRL synergized
      with EGF in activating SHC and ERK and transactivating a luciferase reporter
      driven by c-fos gene enhancer elements, suggesting that PRL allowed markedly
      enhanced EGF signaling. This was accompanied by substantial inhibition of EGF
      induced EGFR downregulation when PRL and EGF cotreatment was compared to EGF
      treatment alone. This effect of PRL was abrogated by ERK pathway inhibitor
      pretreatment. Our data suggest that PRL synergistically augments EGF signaling in
      T47D breast cancer cells at least in part by lessening EGF-induced EGFR
      downregulation and that this effect requires PRL-induced ERK activity and
      threonine phosphorylation of EGFR.

PMID- 16785992
TI  - Cisplatin induces PKB/Akt activation and p38(MAPK) phosphorylation of the EGF
      receptor.
AB  - Cisplatin is an effective DNA-damaging antitumor agent employed for the treatment
      of various human cancers. In this study, we report that Cisplatin activates
      PKB/Akt in several cancer cell lines and that this activation is mediated by
      EGFR, Src and PI3-kinase. Inhibition of PI3-kinase activity decreases the
      survival of the cells exposed to Cisplatin, suggesting that Cisplatin-induced
      PKB/Akt activation may lead to Cisplatin resistance. While investigating the EGFR
      dependent PKB/Akt activation in MDA-MB-468 cells, we found that the EGFR receptor
      undergoes a gel mobility shift upon Cisplatin treatment, which is mediated by
      p38(MAPK). An EGFR, in which threonine 669 was mutated to alanine (A669), is
      phosphorylated by p38(MAPK) to a much lesser extent, suggesting that threonine
      669 is a p38 phosphorylation site. We found that Cisplatin induces EGFR
      internalization, which is mediated by p38(MAPK-)dependent phosphorylation of the
      receptor on threonine 669. Our results identify the EGFR as a new substrate of
      p38 and identify threonine 669 as a new phosphorylation site that regulates EGFR
      internalization. Together, these results suggest that Cisplatin has side effects,
      which may alter the signaling pattern of cancer cells and modulate the desired
      effects of Cisplatin treatment.

PMID- 16785993
TI  - Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated
      phospholipase D activity and contributes to survival signals generated by
      phospholipase D.
AB  - p53 is the most commonly mutated gene in human cancer. Although the loss of tumor
      suppressor functions for p53 in tumorigenesis is well characterized, gain-of
      function p53 mutations observed in most cancers are not as widely appreciated.
      The human breast cancer cell line MDA-MB-231, which has high levels of a mutant
      p53, has high levels of phospholipase D (PLD) activity, which provides a survival
      signal in these cells when deprived of serum growth factors. We report here that
      the mutant p53 in MDA-MB-231 cells is stabilized by the elevated PLD activity in
      these cells. Surprisingly, the survival of MDA-MB-231 cells deprived of serum was
      dependent on the mutant p53. These data indicate that a mutant p53, stabilized by
      elevated PLD activity, can contribute to the suppression of apoptosis in a human
      breast cancer cell line and suggest a rationale for the selection of p53
      mutations early in tumorigenesis to suppress apoptosis in an emerging tumor.

PMID- 16785994
TI  - Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and
      its control of matrix metalloproteinase-2 and -9 expression.
AB  - Squamous cell carcinoma (SCC) is an invasive malignancy of epidermal
      keratinocytes. Surgical excision is currently the main treatment; however, this
      can cause scarring and disfigurement. There is accordingly, an acute need for
      alternative strategies to treat SCC. The transcription factor c-Jun is expressed
      in human SCC and another common form of invasive skin cancer, basal cell
      carcinoma together with the mitogenic marker-proliferating cell nuclear antigen.
      Here, we have employed DNAzymes (catalytic DNA molecules) targeting c-Jun (Dz13)
      to inhibit c-Jun expression in SCC cells. Dz13 inhibits SCC proliferation and
      suppresses solid SCC tumor growth and tumor angiogenesis in severe combined
      immunodeficient mice. We further demonstrate that Dz13 inhibits c-Jun, together
      with matrix metalloproteinase (MMP)-2 and MMP-9 expression in the tumors,
      consistent with DNAzyme inhibition of MMP-2 and MMP-9 gelatinolytic activity by
      zymography. Dz13 also suppressed the expression of vascular endothelial growth
      factor and fibroblast growth factor-2 in the tumors. These findings demonstrate
      that c-Jun regulates SCC growth and suggest that DNAzymes targeting this
      transcription factor may potentially be useful as inhibitors of cutaneous
      carcinoma.

PMID- 16785995
TI  - Directional sensing of a phorbol ester gradient requires CD44 and is regulated by
      CD44 phosphorylation.
AB  - Cancer progression is associated with enhanced directional cell migration, both
      of the tumour cells invading into the stroma and stromal cells infiltrating the
      tumour site. In cell-based assays to study directional cell migration, phorbol
      esters are frequently used as a chemotactic agent. However, the molecular
      mechanism by which these activators of protein kinase C (PKC) result in the
      establishment of a polarized migratory phenotype is not known. Here we show that
      CD44 expression is essential for chemotaxis towards a phorbol ester gradient. In
      an investigation of CD44 phosphorylation kinetics in resting and stimulated
      cells, Ser316 was identified as a novel site of phosphorylation following
      activation of PKC. PKC does not phosphorylate Ser316 directly, but rather
      mediates the activation of downstream Ser316 kinase(s). In transfection studies,
      a phosphorylation-deficient Ser316 mutant was shown to act in a dominant-negative
      fashion to impair chemotaxis mediated by endogenous CD44 in response to a phorbol
      ester gradient. Importantly, this mutation had no effect on random cell motility
      or the ability of cells to migrate directionally towards a cocktail of
      chemoattractants. These studies demonstrate that CD44 functions to provide
      directional cues to migrating cells without affecting the motility apparatus.

PMID- 16785996
TI  - Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin
      treatment.
AB  - We have studied the role of cyclins and cyclin-dependent kinase (CDK) activity in
      apoptosis induced by camptothecin (CPT). In this model, 22% of the cells stain
      for annexin-V at 24 h and then proceed to be 93% positive by 72 h. This time
      window permits the analysis of cyclins in cells that are committed to apoptosis
      but not yet dead. We provide evidence that cyclin protein levels and then
      associated kinase levels increase after CPT treatment. Strikingly, cyclin B1 and
      cyclin E1 proteins are present at the same time in CPT treated HT29 cells.
      Although cyclin B1 and E1 CDK complexes are activated in CPT treated cells, only
      the cyclin B1 complex is required for apoptosis since reduction of cyclin B1 by
      RNAi or roscovitine treatment reduces the number of annexin-V-stained cells. We
      have detected poorly organized chromosomes and phosphorylated histone H3 epitopes
      at the time of maximum cyclin B1/CDK kinase activity in CPT-treated cells, which
      suggests that these cells enter a mitotic catastrophe. Understanding which CDKs
      are required for apoptosis may allow us to better adapt CDK inhibitors for use as
      anti-cancer compounds.

PMID- 16785997
TI  - Enhanced expression of Duffy antigen receptor for chemokines by breast cancer
      cells attenuates growth and metastasis potential.
AB  - In addition to the role in regulating leukocyte trafficking, chemokines recently
      have been shown to be involved in cancer growth and metastasis. Chemokine network
      in tumor neovascularity may be regulated by decoy receptors. Duffy antigen
      receptor for chemokines (DARC) is a specific decoy receptor binding with the
      angiogenic CC and CXC chemokines. To investigate the effects of DARC on the
      tumorigenesis and the metastasis potential of human breast cancer cells, human
      DARC cDNA was reintroduced into the MDA-MB-231 and MDA-MB-435HM cells which have
      a high capability of spontaneous pulmonary metastasis. We demonstrated that DARC
      overexpression induced inhibition of tumorigenesis and/or metastasis through
      interfering with the tumor angiogenesis in vivo. This inhibition is associated
      with decreasing CCL2 protein levels, and MVD and MMP-9 expression in xenograft
      tumors. In human breast cancer samples, we also demonstrated that low expression
      of the DARC protein is significantly associated with estrogen receptor (ER)
      status, MVD, lymph node metastasis, distant metastasis and poor survival. Our
      results suggest for the first time that DARC is a negative regulator of growth in
      breast cancer, mainly by sequestration of angiogenic chemokines and subsequent
      inhibition of tumor neovascularity.

PMID- 16785998
TI  - Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide
      polymorphism arrays.
AB  - Genomic amplification of oncogenes and inactivation of suppressor genes are
      critical in the pathogenesis of human cancer. To identify chromosomal alterations
      associated with hepatocarcinogenesis, we performed allelic gene dosage analysis
      on 36 hepatocellular carcinomas (HCCs). Data from high-density single-nucleotide
      polymorphism arrays were analysed using the Genome Imbalance Map (GIM) algorithm,
      which simultaneously detects DNA copy number alterations and loss of
      heterozygosity (LOH) events. Genome Imbalance Map analysis identified allelic
      imbalance regions, including uniparental disomy, and predicted the coexistence of
      a heterozygous population of cancer cells. We observed that gains of 1q, 5p, 5q,
      6p, 7q, 8q, 17q and 20q, and LOH of 1p, 4q, 6q, 8p, 10q, 13q, 16p, 16q and 17p
      were significantly associated with HCC. On 6q24-25, which contains imprinting
      gene clusters, we observed reduced levels of PLAGL1 expression owing to loss of
      the unmethylated allele. Finally, we integrated the copy number data with gene
      expression intensity, and found that genome dosage is correlated with alteration
      in gene expression. These observations indicated that high-resolution GIM
      analysis can accurately determine the localizations of genomic regions with
      allelic imbalance, and when integrated with epigenetic information, a mechanistic
      basis for inactivation of a tumor suppressor gene in HCC was elucidated.

PMID- 16785999
TI  - Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in
      follicular tumors that progress to poorly differentiated carcinomas.
AB  - Ras oncogenes are frequently mutated in thyroid carcinomas. To verify the role
      played by N-ras in thyroid carcinogenesis, we generated transgenic mice in which
      a human N-ras(Gln61Lys) oncogene (Tg-N-ras) was expressed in the thyroid
      follicular cells. Tg-N-ras mice developed thyroid follicular neoplasms; 11%
      developed follicular adenomas and approximately 40% developed invasive follicular
      carcinomas, in some cases with a mixed papillary/follicular morphology. About 25%
      of the Tg-N-ras carcinomas displayed large, poorly differentiated areas,
      featuring vascular invasion and forming lung, bone or liver distant metastases. N
      ras(Gln61Lys) expression in cultured PC Cl 3 thyrocytes induced thyroid
      stimulating hormone-independent proliferation and genomic instability with
      micronuclei formation and centrosome amplification. These findings support the
      notion that mutated ras oncogenes could be able to drive the formation of thyroid
      tumors that can progress to poorly differentiated, metastatic carcinomas.

PMID- 16786000
TI  - CpG island promoter methylation and silencing of 14-3-3sigma gene expression in
      LNCaP and Tramp-C1 prostate cancer cell lines is associated with methyl-CpG
      binding protein MBD2.
AB  - 14-3-3sigma proteins regulate numerous cellular processes that are important to
      cancer development. One of its biological roles involves G2 cell-cycle arrest
      following DNA damage. It has also been reported that the loss of 14-3-3sigma
      expression via CpG methylation may contribute to malignant transformation by
      impairing the G2 cell-cycle checkpoint function, thereby allowing an accumulation
      of genetic defects. However, how the CpG methylation-dependent silencing
      mechanism works in relation to promoter methylation associated with methyl-CpG
      binding proteins (MeCPs) is still unclear. To better understand the mechanism, we
      first examined the methylation status of the 14-3-3sigma promoter-associated CpG
      islands and 14-3-3sigma gene expression in a subset of prostate cancer cell lines
      using methylation-specific PCR (MSP), an HhaI-based DNA methylation assay, and
      reverse transcription-PCR (RT-PCR). We found that the 14-3-3sigma expression is
      lost in LNCaP and Tramp-C1 prostate cancer cell lines and that this expression is
      restored after treatment with epigenetic silencing modifiers 5-aza-2'
      deoxycytidine (5-aza) and trichostatin A (TSA). These results imply
      transcriptional silencing via promoter-associated CpG methylation. Chromatin
      immunoprecipitation analysis revealed that methyl-CpG-binding protein 2 (MBD2) is
      associated preferentially to the methylated CpG island in the 14-3-3sigma
      promoter in LNCaP and Tramp-C1 cells but not in 14-3-3sigma-expressing PC3 and
      DU145 cells, which contain an unmethylated CpG island in the 14-3-3sigma promoter
      region. The 14-3-3sigma gene silencing because of CpG methylation correlates with
      binding of MBD2. In addition, the activation of 14-3-3sigma gene expression by a
      combination of 5-aza and TSA also involves the release of the MBD2 from the 14-3
      3sigma promoter-methylated CpG island in LNCaP and Tramp-C1 cells. Furthermore,
      MBD2 knockdown by siRNA stimulated 14-3-3sigma expression in LNCaP cells. We also
      investigated whether the loss of 14-3-3sigma expression in LNCaP and Tramp-C1
      cells affects cell proliferation by MTT assays. Interestingly, we observed that
      14-3-3sigma-inactivated LNCaP and Tramp-C1 cells had markedly decreased cell
      proliferation and protein expression of proliferation cell nuclear antigen (PCNA)
      after restoration of 14-3-3sigma expression with 5-aza and TSA treatment. On the
      other hand, the same treatment did not significantly affect 14-3-3sigma-active
      PC3 and DU145 cells, which normally express 14-3-3sigma. Finally, 14-3-3sigma
      knockdown by siRNA resulted in increased proliferation in PC3 and DU145 cells.
      These findings suggest that the transcriptional silencing of the 14-3-3sigma gene
      is caused by promoter CpG island methylation associated with MBD2, and that this
      may play an important role in prostate cancer progression during the invasive and
      metastatic stages of the disease.

PMID- 16786001
TI  - Expression of inappropriate cadherins by epithelial tumor cells promotes
      endocytosis and degradation of E-cadherin via competition for p120(ctn).
AB  - Cadherin cell-cell adhesion proteins play an important role in modulating the
      behavior of tumor cells. E-cadherin serves as a suppressor of tumor cell
      invasion, and when tumor cells turn on the expression of a non-epithelial
      cadherin, they often express less E-cadherin, enhancing the tumorigenic phenotype
      of the cells. Here, we show that when A431 cells are forced to express R
      cadherin, they dramatically downregulate the expression of endogenous E- and P
      cadherin. In addition, we show that this downregulation is owing to increased
      turnover of the endogenous cadherins via clathrin-dependent endocytosis.
      p120(ctn) binds to the juxtamembrane domain of classical cadherins and has been
      proposed to regulate cadherin adhesive activity. One way p120(ctn) may accomplish
      this is to serve as a rheostat to regulate the levels of cadherin. Here, we show
      that the degradation of E-cadherin in response to expression of R-cadherin is
      owing to competition for p120(ctn).

PMID- 16786033
TI  - Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk
      factors for Alzheimer's disease and cardiovascular disease.
AB  - High fat diets and sedentary lifestyles are becoming major concerns for Western
      countries. They have led to a growing incidence of obesity, dyslipidemia, high
      blood pressure, and a condition known as the insulin-resistance syndrome or
      metabolic syndrome. These health conditions are well known to develop along with,
      or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent
      studies have found that most of these disorders can also be linked to an
      increased risk of Alzheimer's disease (AD). To complicate matters, possession of
      one or more apolipoprotein E epsilon4 (APOE epsilon4) alleles further increases
      the risk or severity of many of these conditions, including AD. ApoE has roles in
      cholesterol metabolism and Abeta clearance, both of which are thought to be
      significant in AD pathogenesis. The apparent inadequacies of ApoE epsilon4 in
      these roles may explain the increased risk of AD in subjects carrying one or more
      APOE epsilon4 alleles. This review describes some of the physiological and
      biochemical changes that the above conditions cause, and how they are related to
      the risk of AD. A diversity of topics is covered, including cholesterol
      metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid
      precursor protein metabolism, and in particular their relevance to AD. It can be
      seen that abnormal lipid, cholesterol and glucose metabolism are consistently
      indicated as central in the pathophysiology, and possibly the pathogenesis of AD.
      As diagnosis of mild cognitive impairment and early AD are becoming more
      reliable, and as evidence is accumulating that health conditions such as
      diabetes, obesity, and coronary artery disease are risk factors for AD,
      appropriate changes to diets and lifestyles will likely reduce AD risk, and also
      improve the prognosis for people already suffering from such conditions.

PMID- 16786032
TI  - Impact of complex genetic variation in COMT on human brain function.
AB  - Catechol-O-methyltransferase (COMT) has been shown to be critical for prefrontal
      dopamine flux, prefrontal cortex-dependent cognition and activation. Several
      potentially functional variants in the gene have been identified, but
      considerable controversy exists regarding the contribution of individual alleles
      and haplotypes to risk for schizophrenia, partly because clinical phenotypes are
      ill-defined and preclinical studies are limited by lack of adequate models. Here,
      we propose a neuroimaging approach to overcome these limitations by
      characterizing the functional impact of ambiguous haplotypes on a neural system
      level intermediate phenotype in humans. Studying 126 healthy control subjects
      during a working-memory paradigm, we find that a previously described risk
      variant in a functional Val158Met (rs4680) polymorphism interacts with a P2
      promoter region SNP (rs2097603) and an SNP in the 3' region (rs165599) in
      predicting inefficient prefrontal working memory response. We report evidence
      that the nonlinear response of prefrontal neurons to dopaminergic stimulation is
      a neural mechanism underlying these nonadditive genetic effects. This work
      provides an in vivo approach to functional validation in brain of the biological
      impact of complex genetic variations within a gene that may be critical for its
      clinical association.

PMID- 16786037
TI  - Pilot evaluation of selective serotonin reuptake inhibitor antidepressants in hot
      flash patients under androgen-deprivation therapy for prostate cancer.
AB  - PURPOSE: Hot flash (HF) is a common side effect in prostate cancer patient
      undergoing androgen-deprivation therapy (ADT). In this study, we evaluated the
      efficacy of paroxetine (selective serotonin reuptake inhibitors (SSRIs)) for HF.
      PATIENTS AND METHODS: In total, 10 men with prostate cancer under ADH who were
      suffering with HF entered this study. Self-report questionnaire was used for the
      evaluation. RESULTS: The average rating for HF frequency decreased (P=0.009) and
      HF severity decreased (P=0.0332) also, reported QOL score increased (P=0.0218).
      CONCLUSION: These preliminary data suggest that low dose (10 mg/day) of
      antidepressant paroxetine can be helpful in the treatment of HFs in patients
      under ADT for prostate cancer. Further controlled studies are needed to more
      fully evaluate the efficacy of the SSRIs.

PMID- 16786038
TI  - Androgen deprivation therapy and cardiac function: effects of endurance training.
AB  - PURPOSE: This study examined the effects of an 8-week androgen deprivation
      therapy treatment using Zoladex and an endurance training regimen on cardiac
      function. METHODS: Male Sprague-Dawley rats received either Zoladex or placebo.
      Animals remained sedentary or endurance trained during the drug treatment period.
      On day 57, ex vivo cardiac function was analyzed. RESULTS: Hearts from sedentary
      animals receiving Zoladex possessed significant cardiac dysfunction. However,
      hearts from exercise trained rats receiving Zoladex possessed cardiac function
      values similar to those from hearts from placebo animals. CONCLUSIONS: An 8-week
      treatment with Zoladex promoted cardiac dysfunction. Endurance training during
      Zoladex treatment protected against this cardiac dysfunction.

PMID- 16786039
TI  - Characterization of a method for profiling gene expression in cells recovered
      from intact human prostate tissue using RNA linear amplification.
AB  - Coupling array technology to laser capture microdissection (LCM) has the
      potential to yield gene expression profiles of specific cell populations within
      tissue. However, remaining problems with linear amplification preclude accurate
      expression profiling when using the low nanogram amounts of RNA recovered after
      LCM of human tissue. We describe a novel robust method to reliably amplify RNA
      after LCM, allowing direct probing of 12K gene arrays. The fidelity of
      amplification was demonstrated by comparing the ability of amplified RNA (aRNA)
      versus that of native RNA to identify differentially expressed genes between two
      different cell lines, demonstrating a 99.3% concordance between observations.
      Array findings were validated by quantitative polymerase chain reaction analysis
      of a randomly selected subset of 32 genes. Using LCM to recover normal (N=5
      subjects) or cancer (N=3) cell populations from intact human prostate tissue,
      three differentially expressed genes were identified. Independent investigators
      have previously identified differential expression of two of these three genes,
      hepsin and beta-microseminoprotein, in prostate cancer. Taken together, the
      current study demonstrates that accurate gene expression profiling can readily be
      performed on specific cell populations present within complex tissue. It also
      demonstrates that this approach efficiently identifies biologically relevant
      genes.

PMID- 16786040
TI  - High-dose radiation employing external beam radiotherapy and high-dose rate
      brachytherapy with and without neoadjuvant androgen deprivation for prostate
      cancer patients with intermediate- and high-risk features.
AB  - The role of neoadjuvant androgen deprivation (NAD) in high-risk prostate cancer
      patients receiving high-dose radiotherapy (RT) remains unstudied. To evaluate the
      effect of a course of NAD, we reviewed the experiences of three institutions
      treating these patients with combined RT and high-dose rate brachytherapy (HDR).
      Of 1260 prostate cancer patients with high-risk features (pretreatment prostate
      specific antigen (PSA) > or =10, Gleason Score (GS) > or =7, or T stage > or
      =T2b), 560 received no NAD (n=308) or NAD for < or =6 months (n=252). Median dose
      to the prostate from RT and HDR was 42 and 23 Gy, respectively. Average total
      biologic equivalent prostate dose was >100 Gy (alpha/beta=1.2). Median follow-up
      was 4.3 years. Pretreatment characteristics were similar on chi(2) tables for all
      560 patients treated with or without NAD including pretreatment PSA (P=0.11), GS
      (P=0.4), and clinical T stage (P=0.2). Outcomes worsened for patients receiving
      NAD (5-year distant metastasis (DM) 10 vs 5% (P=0.04); cause-specific survival
      (CSS), 93 vs 98% (P=0.005)). Higher 5-year DM rates and lower CSS occurred in NAD
      patients with a GS between 8 and 10 (n=112 (P=0.03, P=0.02)), pretreatment PSA>
      or =15 (n=136 (P=0.03, P=0.008)), and palpable disease > or =T2a (n=434 (P=0.04,
      P=0.02)). The only two significant risk factors for DM on Cox multivariate
      analysis were GS (P=0.003, HR 2.8) and NAD (P=0.03, HR 2.7). AD given before
      definitive high-dose RT did not benefit prostate cancer patients with
      intermediate- and high-risk features. We favor the use of concurrent/adjuvant AD
      over prolonged NAD for prostate cancer patients for whom AD is clinically
      indicated.

PMID- 16786041
TI  - Muir Torre syndrome and MSH2 mutations: the importance of dermatological
      awareness.

PMID- 16786042
TI  - A prospective study of neurofibromatosis type 1 cancer incidence in the UK.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant condition affecting
      around one in 3000 live births. The manifestations of this condition are
      extremely variable, even within families, and genetic counselling is consequently
      difficult with regard to prognosis. Individuals with NF1 are acknowledged to be
      at increased risk of malignancy. Several studies have previously attempted to
      quantify this risk, but have involved relatively small study populations. We
      present prospective data from 448 individuals with NF1 with a total of 5705 years
      of patient follow-up. These data have been collected via the UK NF1 association
      for patients. Demographic information on the affected individuals was cross
      referenced with UK cancer registry data by the UK Office of National Statistics.
      The overall risk of cancer was 2.7 times higher in this cohort of NF1 patients
      than in the general population (95% confidence interval (CI) 1.9-3.7). The
      cumulative risk of a malignancy by age 50 years was 20% (95% CI 14-29%); beyond
      this age, the risk of cancer was not significantly elevated (P=0.27). The most
      frequent types of cancer were connective tissue (14% risk by age 70, 95% CI 7.8
      24%) and brain tumours (7.9, 95% CI 3.9-16%). There was no statistically
      significant excess of cancers at other sites (P=0.22).

PMID- 16786044
TI  - Mortality in women given diethylstilbestrol during pregnancy.
AB  - We used Cox regression analyses to assess mortality outcomes in a combined cohort
      of 7675 women who received diethylstilbestrol (DES) through clinical trial
      participation or prenatal care. In the combined cohort, the RR for DES in
      relation to all-cause mortality was 1.06 (95% CI = 0.98-1.16), and 1.11 (95% CI =
      1.02-1.21) after adjusting for covariates and omitting breast cancer deaths. The
      RR was 1.07 (95% CI = 0.94-1.23) for overall cancer mortality, and remained
      similar after adjusting for covariates and omitting breast cancer deaths. The RR
      was 1.27 (95% CI = 0.96-1.69) for DES and breast cancer, and 1.38 (95% CI=1.03
      1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12
      in the prenatal care cohort, but the DES-cohort interaction was not significant
      (P = 0.15). Diethylstilbestrol did not increase mortality from gynaecologic
      cancers. In summary, diethylstilbestrol was associated with a slight but
      significant increase in all-cause mortality, but was not significantly associated
      with overall cancer or gynaecological cancer mortality. The association with
      breast cancer mortality was more evident in trial participants, who received high
      DES doses.

PMID- 16786045
TI  - Stem cells and CAM.

PMID- 16786043
TI  - Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of
      the literature with meta-analysis of the survival results.
AB  - Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in
      adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on
      survival in patients with lung cancer. Studies evaluating the survival impact of
      COX-2 in lung cancer, published until December 2005, were selected. Data for
      estimation of individual hazard ratios (HR) for survival were extracted from the
      publications and combined in a pooled HR. Among 14 eligible papers, all dealing
      with non-small-cell lung cancer, 10 provided results for meta-analysis of
      survival data (evaluable studies). Cyclooxygenase-2 positivity was associated
      with reduced survival, improved survival or no statistically significant impact
      in six, one and seven studies, respectively. Combined HR for the 10 evaluable
      studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In
      stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI:
      1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect
      on survival in patients with lung cancer is associated with COX-2 expression, but
      the statistical significance is not reached. This effect is statistically
      significant in stage I, suggesting that COX-2 expression could be useful at early
      stages to distinguish those with a worse prognosis.

PMID- 16786047
TI  - Humor and Laughter May Influence Health: II. Complementary Therapies and Humor in
      a Clinical Population.
AB  - Our results support a connection between sense of humor and self-reported
      physical health, however, it is difficult to determine the relationship to any
      specific disease process. Whereas relationships between sense of humor and self
      reported measures of physical well-being appear to be supported, more research is
      required to determine interrelationships between sense of humor and well-being.

PMID- 16786048
TI  - The Nishino Breathing Method and Ki-energy (Life-energy): A Challenge to
      Traditional Scientific Thinking.
AB  - The breathing method, which was developed and is being taught by Kozo Nishino, a
      Japanese Ki-expert, is for raising the levels of Ki-energy (life-energy or the
      vitality) of an individual. It is neither a therapy nor a healing technique.
      However, many of his students have experienced an improvement in their health,
      and in some cases, they were able to overcome health problems by themselves.
      Since this is an interesting subject from the standpoint of complementary and
      alternative medicine (CAM), we have been collaborating with Nishino to conduct a
      scientific investigation of his Ki-energy. We found that Nishino's Ki-energy can
      inhibit cell division of cancer cells, protect isolated mitochondria from heat
      deterioration and reduce lipid peroxidation in heat-treated mitochondria.
      Although Ki-energy may consist of several different energy forms, we found that
      at least one of them is near-infrared radiation between the wavelength range of
      0.8 and 2.7 microm. Another interesting observation at his school is the Taiki
      practice (paired Ki-practice). During this practice, Nishino can 'move' his
      students without any physical contact. Many of them run, jump or roll on the
      floor when they receive his Ki-energy. We studied this and propose that
      'information' is conveyed through the air between two individuals by Ki-energy.
      This may be called a five sense-independent, life-to-life communication by Ki.
      All of our results suggest that we should re-evaluate the Cartesian dualism
      (separation of mind and body) which has been a fundamental principle of modern
      science for the past three centuries.

PMID- 16786046
TI  - Immunology and homeopathy. 3. Experimental studies on animal models.
AB  - A search of the literature and the experiments carried out by the authors of this
      review show that there are a number of animal models where the effect of
      homeopathic dilutions or the principles of homeopathic medicine have been tested.
      The results relate to the immunostimulation by ultralow doses of antigens, the
      immunological models of the 'simile', the regulation of acute or chronic
      inflammatory processes and the use of homeopathic medicines in farming. The
      models utilized by different research groups are extremely etherogeneous and
      differ as the test medicines, the dilutions and the outcomes are concerned. Some
      experimental lines, particularly those utilizing mice models of immunomodulation
      and anti-inflammatory effects of homeopathic complex formulations, give support
      to a real effect of homeopathic high dilutions in animals, but often these data
      are of preliminary nature and have not been independently replicated. The
      evidence emerging from animal models is supporting the traditional 'simile' rule,
      according to which ultralow doses of compounds, that in high doses are
      pathogenic, may have paradoxically a protective or curative effect. Despite a few
      encouraging observational studies, the effectiveness of the homeopathic
      prevention or therapy of infections in veterinary medicine is not sufficiently
      supported by randomized and controlled trials.

PMID- 16786049
TI  - Low-intensity electromagnetic millimeter waves for pain therapy.
AB  - Millimeter wave therapy (MWT), a non-invasive complementary therapeutic technique
      is claimed to possess analgesic properties. We reviewed the clinical studies
      describing the pain-relief effect of MWT. Medline-based search according to
      review criteria and evaluation of methodological quality of the retrieved studies
      was performed. Of 13 studies, 9 of them were randomized controlled trials (RCTs),
      only three studies yielded more than 3 points on the Oxford scale of
      methodological quality of RCTs. MWT was reported to be effective in the treatment
      of headache, arthritic, neuropathic and acute postoperative pain. The rapid onset
      of pain relief during MWT lasting hours to days after, remote to the site of
      exposure (acupuncture points), was the most characteristic feature in MWT
      application for pain relief. The most commonly used parameters of MWT were the MW
      frequencies between 30 and 70 GHz and power density up to 10 mW cm(-2). The
      promising results from pilot case series studies and small-size RCTs for
      analgesic/hypoalgesic effects of MWT should be verified in large-scale RCTs on
      the effectiveness of this treatment method.

PMID- 16786050
TI  - Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers:
      Modulating Allergic and Infectious Disease Pathology (II).
AB  - Regulatory T (T(reg)) cells maintain dominant control of immune responses to
      foreign materials and microbes. Appropriate T(reg) cell suppression of immune
      responses is essential for the maintenance of efficacious defensive responses and
      the limitation of collateral tissue damage due to excess inflammation. Allergy
      and infection are well studied and frequent afflictions in which T(reg) cells
      play an essential role. As such, they provide excellent models to communicate the
      significance and relevance of T(reg) cells to complementary and alternative
      medicine (CAM).

PMID- 16786051
TI  - Streblus asper Lour. (Shakhotaka): A Review of its Chemical, Pharmacological and
      Ethnomedicinal Properties.
AB  - Streblus asper Lour is a small tree found in tropical countries, such as India,
      Sri Lanka, Malaysia, the Philippines and Thailand. Various parts of this plant
      are used in Ayurveda and other folk medicines for the treatment of different
      ailments such as filariasis, leprosy, toothache, diarrhea, dysentery and cancer.
      Research carried out using different in vitro and in vivo techniques of
      biological evaluation support most of these claims. This review presents the
      botany, chemistry, traditional uses and pharmacology of this medicinal plant.

PMID- 16786052
TI  - Maggot Therapy: The Science and Implication for CAM Part I-History and Bacterial
      Resistance.
AB  - It is now a universally acknowledged fact that maggot therapy can be used
      successfully to treat chronic, long-standing, infected wounds, which have
      previously failed to respond to conventional treatment. Such wounds are typically
      characterized by the presence of necrotic tissue, underlying infection and poor
      healing. Maggot therapy employs the use of freshly emerged, sterile larvae of the
      common green-bottle fly, Phaenicia (Lucilia) sericata, and is a form of
      artificially induced myiasis in a controlled clinical situation. In this review
      article, we will discuss the role of maggots and their preparation for clinical
      use. Maggot therapy has the following three core beneficial effects on a wound:
      debridement, disinfection and enhanced healing. In part I we explore our current
      understanding of the mechanisms underlying these effects.

PMID- 16786053
TI  - The state of the art of traditional arab herbal medicine in the eastern region of
      the mediterranean: a review.
AB  - Historical and current studies indicate that the Eastern region of the
      Mediterranean has been distinguished from other regions by a rich inventory of
      complementary alternative medicine (CAM), in particular herbal medicine. Data
      collected from several surveys and studies indicate that there is a flourishing
      and well-developed trade of herbs. These surveys also reveal that 200-250 herbs
      are used in treating human diseases and are sold or traded in market places in
      the Mediterranean region or internationally. In addition, some of these herbs are
      rare or even endangered species. In regard to the status of the know-how of
      herbalists, unfortunately, herbal medicine in our region is mostly prescribed by
      ethnopharmacologists symptomatically-based on signs and symptoms alone, rather
      than as a result of a full understanding of the underlying disease. In some
      cases, herbs used today may not even correspond to the plants described
      originally in the old literature, as the former are cultivated from herbs that
      went through different breeding procedures throughout several centuries. This
      article presents a systematic review of both the state of the art of traditional
      Arab herbal medicine and the status of the know-how of Arab herbalists.

PMID- 16786054
TI  - Epicatechins Purified from Green Tea (Camellia sinensis) Differentially Suppress
      Growth of Gender-Dependent Human Cancer Cell Lines.
AB  - The anticancer potential of catechins derived from green tea is not well
      understood, in part because catechin-related growth suppression and/or apoptosis
      appears to vary with the type and stage of malignancy as well as with the type of
      catechin. This in vitro study examined the biological effects of epicatechin
      (EC), epigallocatechin (EGC), EC 3-gallate (ECG) and EGC 3-gallate (EGCG) in cell
      lines from human gender-specific cancers. Cell lines developed from organ
      confined (HH870) and metastatic (DU145) prostate cancer, and from moderately
      (HH450) and poorly differentiated (HH639) epithelial ovarian cancer were grown
      with or without EC, EGC, ECG or EGCG. When untreated cells reached confluency,
      viability and doubling time were measured for treated and untreated cells.
      Whereas EC treatment reduced proliferation of HH639 cells by 50%, EGCG suppressed
      proliferation of all cell lines by 50%. ECG was even more potent: it inhibited
      DU145, HH870, HH450 and HH639 cells at concentrations of 24, 27, 29 and 30
      microM, whereas EGCG inhibited DU145, HH870, HH450 and HH639 cells at
      concentrations 89, 45, 62 and 42 microM. When compared with EGCG, ECG more
      effectively suppresses the growth of prostate cancer and epithelial ovarian
      cancer cell lines derived from tumors of patients with different stages of
      disease.

PMID- 16786055
TI  - Bioactive constituents of brazilian red propolis.
AB  - In a new propolis type, red Brazilian propolis, 14 compounds were identified (six
      of them new for propolis), among them simple phenolics, triterepenoids,
      isoflavonoids, prenylated benzophenones and a naphthoquinone epoxide (isolated
      for the first time from a natural source). Three of the major components
      demonstrated significant antimicrobial activity, and two (obtained as inseparable
      mixture) possessed radical scavenging activity against 1,1-diphenyl-2
      picrylhydrazyl (DPPH).

PMID- 16786056
TI  - Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible
      Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract.
AB  - We aimed to compare the anti-inflammatory activities of six species of Curcuma
      drugs using adjuvant arthritis model mice. When orally administered 1 day before
      the injection of adjuvant, the methanol extract of Curcuma phaeocaulis
      significantly inhibited paw swelling and the serum haptoglobin concentration in
      adjuvant arthritis mice. Also when orally administered 1 day after the injection
      of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited
      paw swelling. Other Curcuma species (Curcuma longa, Curcuma wenyujin, Curcuma
      kwangsiensis, Curcuma zedoaria and Curcuma aromatica) had no significant
      inhibitory effects on adjuvant-induced paw swelling. Cyclooxygenase (COX)-2
      activity was significantly inhibited by the methanol extract of C. phaeocaulis.
      Curcuminoids' (curcumin, bis-demethoxycurcumin and demethoxycurcumin) were rich
      in C. longa, but less in C. phaeocaulis and C. aromatica, not in C. wenyujin, C.
      kwangsiensis and C. zedoaria, suggesting that curcuminoids' contents do not
      relate to inhibition of arthritis swelling. Therefore, C. phaeocaulis may be a
      useful drug among Curcuma species for acute inflammation, and the active
      constituents of C. phaeocaulis are not curcuminoids.

PMID- 16786057
TI  - Antimicrobial Activity of Indigofera suffruticosa.
AB  - Various organic and aqueous extracts of leaves of Indigofera suffruticosa Mill
      (Fabaceae) obtained by infusion and maceration were screened for their
      antibacterial and antifungal activities. The extracts were tested against 5
      different species of human pathogenic bacteria and 17 fungal strains by the agar
      solid diffusion method. Most of the extracts were devoid of antifungal and
      antibacterial activities, except the aqueous extract of leaves of I. suffruticosa
      obtained by infusion, which showed strong inhibitory activity against the Gram
      positive bacteria Staphylococcus aureus with a minimal inhibitory concentration
      (MIC) of 5000 microg ml(-1). The MIC values to dermatophyte strains were 2500
      microg ml(-1) against Trichophyton rubrum (LM-09, LM-13) and Microsporum canis.
      This study suggests that aqueous extracts of leaves of I. suffruticosa obtained
      by infusion can be used in the treatment of skin diseases caused by
      dermatophytes.

PMID- 16786058
TI  - Evaluation of Cytotoxic Effects of Dichloromethane Extract of Guduchi (Tinospora
      cordifolia Miers ex Hook F & THOMS) on Cultured HeLa Cells.
AB  - Extracts of Tinospora cordifolia (TCE) have been shown to possess anti-tumor
      properties, but the mechanism of the anti-tumor function of TCE is poorly
      understood. This investigation elucidates the possible mechanism underlying the
      cytotoxic effects of dichlormethane extracts of TCE, after selecting optimal
      duration and concentration for treatment. HeLa cells were exposed to various
      concentrations of TCE, which has resulted in a concentration-dependent decline in
      the clonogenicity, glutathione-S-transferase (GST) activity and a concentration
      dependent increase in lipid peroxidation (TBARS) with a peak at 4 h and lactate
      dehydrogenase (LDH) release with a peak at 2 h. Our results suggest that the
      cytotoxic effect of TCE may be due to lipid peroxidation and release of LDH and
      decline in GST.

PMID- 16786059
TI  - Satisfaction with Family Physicians and Specialists and the use of Complementary
      and Alternative Medicine in Israel.
AB  - Higher utilization of complementary and alternative medicine (CAM) is commonly
      explained by dissatisfaction or disappointment with conventional medical
      treatment. To explore, at two points in time in Israel, the associations between
      six domains of satisfaction (attitude, length of visits, availability,
      information sharing, perceived quality of care and overall) with conventional
      family physicians' and specialists' services and the likelihood of consulting CAM
      providers. This is a secondary analysis of interviews, which were conducted with
      2000 persons in 1993 and 2500 persons in 2000, representing the Israeli Jewish
      urban population aged 45-75 in those years. Bivariate and multivariate analyses
      were used in the investigation. In 1993, users of CAM were less satisfied than
      non-users with both family physicians' and specialists' care. Lower satisfaction
      with the attitude of, the amount of information sharing by and in general with
      family physicians, and with the length of visits and perceived quality of care of
      specialists were significantly associated with CAM use. In 2000, lower
      satisfaction with specialists' attitude, length of visits, availability and in
      general was significantly related to the use of CAM. Lower satisfaction with
      family physicians and specialists is significantly associated with consulting CAM
      providers. However, with CAM becoming a mainstream medical care specialty in its
      own, lower satisfaction with conventional medicine specialists becomes the most
      important factor.

PMID- 16786060
TI  - Bilateral integrative medicine, obviously.
AB  - Unstated and unacknowledged bias has a profound impact on the nature and
      implementation of integrative education models. Integrative education is the
      process of training conventional biomedical and traditional Chinese medicine
      practitioners in each tradition such that patient care may be effectively
      coordinated. A bilateral education model ensures that students in each tradition
      are cross-taught by experts from the 'other' tradition, imparting knowledge and
      values in unison. Acculturation is foundational to bilateral integrative medical
      education and practice. Principles are discussed for an open-minded bilateral
      educational model that can result in a new generation of integrative medicine
      teachers.

PMID- 16786061
TI  - Developing CAM Research Capacity for Complementary Medicine.
AB  - This article describes initiatives that have been central to the development of
      complementary and alternative medicine (CAM) research capacity in the United
      Kingdom, Canada and the United States over the last decade. While education and
      service delivery are essential parts of the development of CAM, this article will
      focus solely on the development of research strategy. The development of CAM
      research has been championed by both patients and politicians, primarily so that
      we may better understand the popularity and apparent effectiveness of these
      therapies and support integration of safe and effective CAM in health care. We
      hope that the perspective provided by this article will inform future research
      policy.

PMID- 16786063
TI  - DFT studies of the methyl exchange reaction between Cp2M-CH3 or Cp*2M-CH3 (Cp =
      C5H5, Cp* = C5Me5, M = Y, Sc, Ln) and CH4. Does M ionic radius control the
      reaction?
AB  - The activation energies for the methyl exchange reactions between Cp2M-CH3 and H
      CH3 have been calculated for M = Sc, Y and representative metals of the
      lanthanide family (La, Ce, Sm, Ho, Yb and Lu) with DFT(B3PW91) calculations with
      large-core pseudopotentials for M. The sigma-bond metathesis reactions are
      calculated to have lower activation energies for early lanthanides than for late
      lanthanides and any of group 3 metals. The relative activation barriers are
      analyzed using the NBO charge distributions in the reactant and in the transition
      states. It is shown that the methane needs to be polarized in the transition
      state as H((+delta))-CH3((-delta)) by the reactant, because this sigma-bond
      metathesis is best viewed as heterolytic cleavage of methane, leading to a proton
      transfer between two methyl groups in the field of an electropositive M metal.
      Early lanthanides, which are involved in strongly ionic metal-ligands bonds are
      thus associated with the lowest activation energies. The ionic radius and the
      steric effects influence the relative rates of reaction for the complexes of Sc,
      Y and Lu. In agreement with earlier works of Sherer et al., the experimental
      reactivity trends found by Tilley are reproduced best with Cp*2M-CH3 (Cp* =
      C5Me5) rather than Cp2M-CH3 (Cp = C5H5) because the steric bulk of C5Me5
      deactivates most the complex where the metal has the smallest ionic radius (Sc).
      While the steric effects and the influence of the metal ionic radius cannot be
      neglected, these factors are not the only ones involved in determining the
      activation barriers of the sigma-bond metathesis reaction.

PMID- 16786062
TI  - Intelligent design: the de novo engineering of proteins with specified functions.
AB  - One of the principal successes of de novo protein design has been the creation of
      small, robust protein-cofactor complexes which can serve as simplified models, or
      maquettes, of more complicated multicofactor protein complexes commonly found in
      nature. Different maquettes, generated by us and others, recreate a variety of
      aspects, or functional elements, recognized as parts of natural enzyme function.
      The current challenge is to both expand the palette of functional elements and
      combine and/or integrate them in recreating familiar enzyme activities or
      generating novel catalysis in the simplest protein scaffolds.

PMID- 16786064
TI  - Photomagnetic properties of iron(II) spin crossover complexes of 2,6
      dipyrazolylpyridine and 2,6-dipyrazolylpyrazine ligands.
AB  - The photomagnetic properties of the following iron(II) complexes have been
      investigated: [Fe(L1)2][BF4]2, [Fe(L2)2][BF4]2, [Fe(L2)2][ClO4]2,
      [Fe(L3)2][BF4]2, [Fe(L3)2][ClO4]2 and [Fe(L4)2][ClO4]2 (L1 = 2,6-di{pyrazol-1
      yl}pyridine; L2 = 2,6-di{pyrazol-1-yl}pyrazine; L3 = 2,6-di{pyrazol-1-yl}-4
      {hydroxymethyl}pyridine; and L4 = 2,6-di{4-methylpyrazol-1-yl}pyridine).
      Compounds display a complete thermal spin transition centred between 200-300 K,
      and undergo the light-induced excited spin state trapping (LIESST) effect at low
      temperatures. The T(LIESST) relaxation temperature of the photoinduced high-spin
      state for each compound has been determined. The presence of sigmoidal kinetics
      in the HS --> LS relaxation process, and the observation of LITH hysteresis loops
      under constant irradiation, demonstrate the cooperative nature of the spin
      transitions undergone by these materials. All the compounds in this study follow
      a previously proposed linear relation between T(LIESST) and their thermal spin
      transition temperatures T(1/2): T(LIESST) = T(0)- 0.3T(1/2). T(0) for these
      compounds is identical to that found previously for another family of iron(II)
      complexes of a related tridentate ligand, the first time such a comparison has
      been made. Crystallographic characterisation of the high- and low-spin forms, the
      light-induced high-spin state, and the low-spin complex [Fe(L4)2][BF4]2, are
      described.

PMID- 16786065
TI  - Active site structures and the redox properties of blue copper proteins: atomic
      resolution structure of azurin II and electronic structure calculations of
      azurin, plastocyanin and stellacyanin.
AB  - Understanding how the active site structures of blue copper proteins determine
      their redox properties is the central structure-function relationship question of
      this important class of protein, also referred to as cupredoxins. We here
      describe both experimental and computational studies of azurin, plastocyanin and
      stellacyanin designed to define more accurately the geometric structures of the
      active site of the reduced and oxidized species, and thus to understand how these
      structures determine the redox potentials of these proteins. To this end the
      crystal structure of reduced azurin II has been determined at an atomic
      resolution of 1.13 Angstrom and is presented here. Co-ordinates and structure
      factors have been deposited in the RCSB Protein Data Bank with accession codes
      2ccw and r2ccwsf respectively. The improved accuracy provided by the atomic
      resolution for the metal stereochemistry are utilised in conjunction with the
      EXAFS data for theoretical calculations. Multilevel calculations involving
      density functional theory and molecular mechanical potentials are used to predict
      both the geometric and electronic structure of the active sites of azurin,
      plastocyanin and stellacyanin and to estimate the relative redox potentials of
      these three proteins. We have also compared the relative energies of the
      structures obtained from experiment at varying resolutions, and from the isolated
      and embedded cluster calculations. We find significant energy differences between
      low and high (atomic) resolution structures arising primarily due to inaccuracies
      in the Cu-ligand distances in the lower resolution structures, emphasising the
      importance of accurate, very high resolution structural information. QM/MM
      structures are only approximately 1 kcal mol(-1) lower in energy than the 1.13
      Angstrom structure while the optimized gas phase structure is 13.0 kcal mol(-1)
      lower in energy.

PMID- 16786066
TI  - DFT calculations of d0 M(NR)(CHtBu)(X)(Y) (M = Mo, W; R = CPh3, 2,6-iPr-C6H3; X
      and Y = CH2tBu, OtBu, OSi(OtBu)3) olefin metathesis catalysts: structural,
      spectroscopic and electronic properties.
AB  - DFT(B3PW91) calculations have been carried out to rationalise the structural,
      electronic and spectroscopic properties of Mo and W imido M(NR1)(CHR2)(X)(Y)
      olefin metathesis catalysts by using either simplified or actual ligands of the
      experimental complexes. The calculated structures, energetics (preference for the
      syn isomer and alkylidene rotational barrier for the syn/anti interconversion),
      and spectroscopic properties (NMR J(C-H) coupling constants) are in good
      agreement with available experimental data. Additionally, the alkylidene nu(C-H)
      stretching frequencies, not available experimentally, have been calculated. These
      quasi-tetrahedral complexes have a linear imido group and a C-H alkylidene
      agostic interaction, which stabilizes the syn isomer. Whether looking at
      M(NR1)(CHR2)(X)(Y), M = Mo, W, or the isolobal Re complexes, Re(CR1)(CHR2)(X)(Y),
      a linear correlation is obtained between both the alkylidene nu(C-H) stretching
      frequencies and J(C-H) coupling constants with the calculated alkylidene C-H bond
      lengths. These correlations show that the strength of the alpha-C-H agostic
      interaction increases from alkylidyne Re to imido group 6 complexes and from Mo
      to W. The NBO and AIM Bader analyses show firstly that the imido and alkylidyne
      groups are both triply bonded to the metal, but that the triply bonded imido
      ligand is a weaker electron donor than the alkylidyne, hence the stronger alpha-C
      H agostic interaction for group 6 imido complexes. Secondly, one of the pi bonds
      of the triply bonded ligand is weakened at the transition state of the alkylidene
      rotation: while no lone pair is formed, the metal-ligand triple bond is
      polarized. This is more favourable for an imido than for an alkylidyne ligand,
      hence the lower alkylidene rotational barrier for the former complexes.
      Conversely, the aryl imido is even less of an electron donor than the alkyl imido
      group, which in turn strengthens the alpha-C-H agostic interaction and lowers the
      alkylidene rotational barrier even more.

PMID- 16786067
TI  - A new chiral lanthanide NMR probe for the determination of the enantiomeric
      purity of alpha-hydroxy acids and the absolute configuration of alpha-amino acids
      in water.
AB  - A water-soluble, enantiopure lanthanide complex, SSS-[Ln x L3], has been assessed
      as an effective chiral derivatizing agent for the determination of the
      enantiomeric purity of alpha-hydroxy acids in aqueous solution. The complex
      displays superior chemical shift non-equivalence (DeltaDeltadelta approximately 2
      11 ppm) for the diastereomeric resonances of interest compared to lanthanide
      shift reagents reported in the literature (DeltaDeltadelta <0.1 ppm, typically).
      1H NMR studies have also revealed that SSS-[Ln x L3] can be used to determine the
      absolute configuration of alpha-amino acids at physiological pH, in water. The
      ability of SSS-[Ln x L3] to signal anion binding and, in particular, to
      distinguish between diastereomers through optical techniques such as lanthanide
      luminescence and circular dichroism has also been assessed.

PMID- 16786068
TI  - A study of the formation, purification and application as a SWNT growth catalyst
      of the nanocluster [HxPMo12O40[subset]H4Mo72Fe30(O2CMe)15O254(H2O)98].
AB  - The synthetic conditions for the isolation of the iron-molybdenum nanocluster
      FeMoC [HxPMo12O40 [subset]H4Mo72Fe30(O2CMe)15O254(H2O)98], along with its
      application as a catalyst precursor for VLS growth of SWNTs have been studied. As
      prepared FeMoC is contaminated with the Keplerate cage
      [H4Mo72Fe30(O2CMe)15O254(H2O)98] without the Keggin [HxPMo12O40]n- template,
      however, isolation of pure FeMoC may be accomplished by Soxhlet extraction with
      EtOH. The resulting EtOH solvate is consistent with the replacement of the water
      ligands coordinated to Fe being substituted by EtOH. FeMoC-EtOH has been
      characterized by IR, UV-vis spectroscopy, MS, XPS and 31P NMR. The solid-state
      31P NMR spectrum for FeMoC-EtOH (delta-5.3 ppm) suggests little effect of the
      paramagnetic Fe3+ centers in the Keplerate cage on the Keggin ion's phosphorous.
      The high chemical shift anisotropy, and calculated T1 (35 ms) and T2 (8 ms)
      values are consistent with a weak magnetic interaction between the Keggin ion's
      phosphorus symmetrically located within the Keplerate cage. Increasing the FeCl2
      concentration and decreasing the pH of the reaction mixture optimizes the yield
      of FeMoC. The solubility and stability of FeMoC in H2O and MeOH-H2O is
      investigated. The TGA of FeMoC-EtOH under air, Ar and H2 (in combination with
      XPS) shows that upon thermolysis the resulting Fe : Mo ratio is highly dependent
      on the reaction atmosphere: thermolysis in air results in significant loss of
      volatile molybdenum components. Pure FeMoC-EtOH is found to be essentially
      inactive as a pre-catalyst for the VLS growth of single-walled carbon nanotubes
      (SWNTs) irrespective of the substrate or reaction conditions. However, reaction
      of FeMoC with pyrazine (pyz) results in the formation of aggregates that are
      found to be active catalysts for the growth of SWNTs. Activation of FeMoC may
      also be accomplished by the addition of excess iron. The observation of prior
      work's reported growth of SWNTs from FeMoC is discussed with respect to these
      results.

PMID- 16786069
TI  - Design, synthesis and photophysical studies of an emissive, europium based,
      sensor for zinc.
AB  - The synthesis of the probe complex . and photophysical studies in aqueous media
      are described. . is designed to be luminescently responsive to Zn(II) in the
      presence of a competitive ionic mixture at pH 7.4. The structure of the complex
      is based upon a carboxylate functionalized azamacrocycle and possesses a
      chromophoric bis-picolyl unit for binding Zn(II). The effect on both ligand
      fluorescence and Eu(III) phosphorescence was investigated in the presence and
      absence of Zn(II). The study revealed that binding Zn(II) increased the intensity
      of ligand fluorescence and modulated the inner sphere hydration number of Eu(III)
      (q increases from 0 to 2). This modulation in coordination environment induced
      pronounced changes in the form of the steady state spectra allowing the presence
      of Zn(II) to be signalled by both changes in emission intensity and lifetime.

PMID- 16786070
TI  - Extended three-dimensional supramolecular architectures derived from trinuclear
      (bis-beta-diketonato)copper(II) metallocycles.
AB  - Neutral trinuclear (triangular) copper(II) complexes of type [Cu3L3]
      incorporating the 1,4-aryl linked bis-beta-diketonato bridging ligands, 1,1-(1,4
      phenylene)-bis(butane-1,3-dione) (H2L2), 1,1-(1,4-phenylene)-bis(pentane-1,3
      dione) (H2L3) and 1,1-(1,4-phenylene)-bis(4,4-dimethylpentane-1,3-dione) (H2L4)
      have been demonstrated to react with selected heterocyclic nitrogen donor bases
      to generate extended supramolecular architectures whose structures have been
      confirmed by X-ray diffraction. Thus on reaction with 4,4'-bipyridine (bipy),
      [Cu3(L2)3] yields polymeric structures of type {[Cu3(L2)3(bipy)(THF)] x 2.75THF}n
      and {[Cu3(L2)3(bipy)(THF)] x bipy x 0.75THF}(n) while with pyrazine (pyz),
      {[Cu3(L2)3(pyz)] x 0.5THF}n was obtained. Each of these extended structures
      contain alternating triangle/linker units in a one-dimensional polymeric chain
      arrangement in which two of the three copper sites in each triangular 'platform'
      are formally five-coordinate through binding to a heterocyclic nitrogen atom.
      Interaction of the multifunctional linker unit hexamethylenetetramine (hmt) with
      [Cu3(L3)3] afforded an unusual, chiral, three-dimensional molecular framework of
      stoichiometry [Cu3(L3)3(hmt)]n. The latter incorporates the trinuclear units
      coordinated to three triply bridging hmt units. In marked contrast to the
      formation of the above structures incorporating bifunctional linker units and
      five-coordinate metal centres, the trinuclear platform [Cu3(L2)3] reacts with the
      stronger difunctional base 1,4-diazabicyclo[2.2.2]-octane (dabco) to yield a
      highly symmetric trigonal columnar species of type {[Cu3(L4)3(dabco)3] x 3H2O}n
      in which each copper centre is octahedrally coordinated.

PMID- 16786071
TI  - Inert benzothiazole functionalised ruthenium(II) complexes; potential DNA hairpin
      binding agents.
AB  - The two enantiomers of [Ru(bpy)2(bbtb)]2+{bpy = 2,2'-bipyridine; bbtb = 4,4'
      bis(benzothiazol-2-yl)-2,2'-bipyridine} have been isolated and fully
      characterised. Both enantiomers have been shown to have a strong association with
      calf thymus DNA by UV/visible absorption, emission and CD spectroscopy, with the
      Lambda enantiomer having the greater affinity. The binding of both enantiomeric
      forms of [Ru(bpy)2(Me2bpy)]2+ and [Ru(bpy)2(bbtb)]2+{Me(2)bpy = 4,4'-dimethyl
      2,2'-bipyridine} to a range of oligonucleotides, including an octadecanucleotide
      and an icosanucleotide which contain hairpin-sequences, have been studied using a
      fluorescent intercalator displacement (FID) assay. The complex [Ru(bpy)2(bbtb)]2+
      exhibited an interesting association with hairpin oligonucleotides, again with
      the Lambda enantiomer binding more strongly. A (1)H NMR spectroscopic study of
      the binding of both enantiomers of [Ru(bpy)2(bbtb)]2+ to the icosanucleotide
      d(CACTGGTCTCTCTACCAGTG) was conducted. This sequence contains a seven-base-pair
      duplex stem and a six-base hairpin-loop. The investigation gave an indication of
      the relative binding of the complexes between the two different regions (duplex
      and secondary structure) of the oligonucleotide. The results suggest that both
      enantiomers bind at the hairpin, with the ruthenium centre located at the stem
      loop interface. NOE studies indicate that one of the two benzothiazole
      substituents of the bbtb ligand projects into the loop-region. A simple model of
      the metal complex/oligonucleotide adduct was obtained by means of molecular
      modelling simulations. The results from this study suggest that benzothiazole
      complexes derived from inert polypyridine ruthenium(II) complexes could lead to
      the development of new fluorescent DNA hairpin binding agents.

PMID- 16786072
TI  - Titanium-salen complexes as initiators for the ring opening polymerisation of rac
      lactide.
AB  - A family of bis(iso-propoxide) titanium(IV) complexes supported by tetradentate
      Schiff base (salen) ligands has been synthesised and characterised, including a
      structural determination of N,N'-bis(6'-methylenimino-2',4'-di-tert
      butylphenoxy)cyclohexyl-(1R,2R)-diamino titanium(IV) bis(iso-propoxide). Their
      suitability for initiating the ring-opening polymerisation of rac-lactide has
      been investigated. Polymerisation activities are shown to correlate with the
      electronic properties of the substituents within the salen ligand. In contrast to
      aluminium-salen initiators, electron-withdrawing substituents on the Schiff base
      ligand have a detrimental influence upon polymerisation activities, whereas the
      use of electron-donating alkoxy-functionalized ligands has allowed the highest
      recorded activity to date for a titanium-based initiator.

PMID- 16786073
TI  - Polyhedral C2@Agn cages distorted by ancillary pyridine N-oxide ligands in silver
      acetylenediide complexes.
AB  - Reactions of the pyridine N-oxide ligands L, L2 and L3 with the silver
      acetylenediide-containing system under hydrothermal conditions gave rise to four
      silver-acetylenediide complexes bearing interesting C2@Agn motifs:
      (Ag2C2)2(AgCF3CO2)8(L1)3.5 (1), (Ag2C2)2(AgCF3CO2)8(L2)2 (2),
      (Ag2C2)(AgCF3CO2)4(L3) (3) and [(Ag7(C2)(CF3SO3)3(L3)2(H2O)2] x 2CF3SO3 (4) (L =
      nicotinic acid N-oxide, L(1) = pyridine N-oxide, L2 = 1,2-bis(4-pyridyl)ethane
      N,N'-dioxide, L3 = 1,3-bis(4-pyridyl)propane N,N'-dioxide), which exhibit new
      distorted polyhedral C2@Agn cage motifs. Complex 1 has a pair of acetylenediide
      dianions encapsulated in a Ag(14) aggregate composed of three polyhedral parts,
      whereas 2 contains an irregular (C2)2@Ag13 double cage. In 3, the basic building
      unit is a centrosymmetric (C2)2@Ag12 double cage with each component single cage
      taking the shape of a highly distorted triangulated dodecahedron with one missing
      vertex. As to complex 4, the core is a C2@Ag7 single cage in the form of a
      slightly distorted monocapped trigonal prism with four cleaved edges that include
      all three vertical sides. Furthermore, in the silver-rich environment, the pyO
      type ligands are induced to exhibit unprecedented coordination modes, such as the
      mu(5)-O,O,O,O',O' ligation mode of L2 in 2 and the mu4-O,O,O',O' mode of L3 in 3
      and 4.

PMID- 16786074
TI  - A modular approach to anion binding podands: adaptability in design and synthesis
      leads to adaptability in properties.
AB  - Progress in the development of a modular approach towards flexible anion-binding
      and sensing systems is reviewed within the context of related developments in
      conformationally flexible anion- and salt-binding hosts. The transferability of
      concepts and structural features across chemically distinct systems is emphasised
      along with the use of modular components in polymer and gel-phase systems.

PMID- 16786075
TI  - A series of new structural models for the OEC in photosystem II.
AB  - A new series of MMn(II-III)(4) clusters (M = Na, Ca) has been structurally
      characterised and their relevance to understanding the oxygen evolving centre of
      photosystem II is discussed.

PMID- 16786076
TI  - X-Ray crystallographic and EPR spectroscopic characterization of a pyrrolidine
      adduct of Y3N@C80.
AB  - Crystallographic data for the pyrrolidine adduct Y3N@C80C4H9N x 2.5CS2 reveals a
      slightly pyramidalized Y3N unit with idealized mirror symmetry that straddles the
      site of addition but does not directly interact with the addend.

PMID- 16786077
TI  - Photochromism of a diarylethene charge-transfer complex: photochemical control of
      intermolecular charge-transfer interaction.
AB  - A diarylethene derivative bearing a phenylenediamine group formed radical ions
      with an electron acceptor molecule in solution, and the concentration of the
      radical ions was modulated by the photochromic reaction of the diarylethene,
      reflecting the difference in the electron-donating character between the open-
      and closed-ring isomers.

PMID- 16786078
TI  - Notable norbornene (NBE) incorporation in ethylene-NBE copolymerization catalysed
      by nonbridged half-titanocenes: better correlation between NBE incorporation and
      coordination energy.
AB  - CpTiCl2(N=CtBu2) exhibits both remarkable catalytic activity and efficient
      norbornene (NBE) incorporation for ethylene-NBE copolymerization: the NBE
      incorporation by Cp'TiCl2(X) (X = N=CtBu2, O-2,6-iPr2C6H3; Cp' = Cp, C5Me5,
      indenyl) was related to the calculated coordination energy after ethylene
      insertion.

PMID- 16786079
TI  - A novel porous carbon based on diatomaceous earth.
AB  - The production and characterisation of a carbon negative of diatomaceous earth
      which has a highly intricate and novel porous structure.

PMID- 16786080
TI  - Lithium amide conjugate addition for the asymmetric synthesis of 3
      aminopyrrolidines.
AB  - Conjugate addition of homochiral lithium amides to methyl 4-(N-benzyl-N
      allylamino)but-2-enoate, chemoselective N-deprotection and concomitant
      cyclisation, followed by enolate functionalisation and deprotection allows access
      to syn- and anti-3,4-disubstituted aminopyrrolidines in > 98% d.e. and > 98% e.e.

PMID- 16786081
TI  - Chemo-differentiating MCRs based on alpha-ketoesters and terminal alkynoates. A
      homoaldol-based ABB' system.
AB  - A novel ABB' 3 component reaction (3-CR) system based on the organocatalyzed
      homoaldolic condensation of alpha-ketoesters in the presence of terminal
      conjugated alkynoates is described.

PMID- 16786082
TI  - Hydrogen adsorption in microporous hypercrosslinked polymers.
AB  - A microporous hypercrosslinked polymer resin was synthesized and shown to adsorb
      3.04 wt.% hydrogen at 77 K and 15 bar; this represents the highest level of
      hydrogen adsorption yet observed for an organic polymer.

PMID- 16786083
TI  - First C-3 lithiation of DMAP: a new entry into chemical tuning of acylation
      catalysts.
AB  - A TMSCH2Li-based reagent promoted the first C-3 lithiation of DMAP opening a
      direct access to functional diversity in acylation catalysts.

PMID- 16786084
TI  - Two-dimensional LNA/DNA arrays: estimating the helicity of LNA/DNA hybrid duplex.
AB  - We measured the helical repeats of a non-natural nucleic acid, locked nucleic
      acid (LNA), by incorporating LNA strands into the outer arms of a DNA double
      crossover (DX) molecule; atomic force microscopy (AFM) imaging of the two
      dimensional (2D) arrays self-assembled from these DX molecules allows us to
      derive the helical repeat of the LNA/DNA hetero-duplex to be 13.2 +/- 0.9 base
      pairs per turn.

PMID- 16786085
TI  - Sulfur-capped cyclodextrins: a new class of cavitands with extroverted as well as
      introverted donor functionalities.
AB  - Ansa-cyclodextrins were obtained in high yields by reaction of sodium sulfide
      with A,B-di- or A,B,D,E-tetramesylated alpha-CD precursors; the resulting
      thiocavitands are suitable for forming nanotubular molecules, as well as for
      hosting metal-organic fragments.

PMID- 16786086
TI  - Blue emitting polyaniline.
AB  - A family of stable polyaniline (PANI) derivatives exhibiting deep blue
      photoluminescence (PL) has been prepared. The synthetic strategy provides a
      unique way to functionalize the PANI backbone.

PMID- 16786088
TI  - Thermodynamic and kinetic factors in the hydrothermal synthesis of hybrid
      frameworks: zinc 4-cyclohexene-1,2-dicarboxylates.
AB  - Experimental and computational studies indicate that the formation of a series of
      zinc 4-cyclohexene-1,2-dicarboxylates takes place under thermodynamic rather than
      kinetic control.

PMID- 16786087
TI  - Extended ethidium bromide analogue as a triple helix intercalator: synthesis,
      photophysical properties and nucleic acids binding.
AB  - Ethidium bromide has been extended by fusing an additional aromatic ring
      resulting in a larger intercalator with increased affinity for poly r(A) x r(U),
      poly d(A) x d(T) and triple helices when compared to the parent heterocycle.

PMID- 16786089
TI  - Enyne ring-closing metathesis on heteroaromatic cations.
AB  - Cationic heteroaromatic enynes have been employed as substrates in enyne ring
      closing metathesis, under an atmosphere of ethylene and using the Hoveyda-Grubbs
      catalyst, for the first time; the reaction affords new 1-vinyl- and 2-vinyl
      substituted 3,4-dihydroquinolizinium salts, useful precursors for biologically
      relevant cations based on the quinolinizium system.

PMID- 16786090
TI  - A new class of laser dyes, 2-oxa-bicyclo[3.3.0]octa-4,8-diene-3,6-diones, with
      unity fluorescence yield.
AB  - A new class of highly fluorescent dyes, 4,8-diphenyl-2-oxa-bicyclo[3.3.0]octa-4,8
      diene-3,6-diones (1a-c), have been synthesized, they all exhibit unity
      fluorescence quantum yield and short radiative lifetime (< 4 ns) in common
      organic solvents and have demonstrated remarkable amplified spontaneous emission
      with a gain efficiency of > 10.

PMID- 16786091
TI  - Surfactant ionic liquid-based microemulsions for polymerization.
AB  - Surfactants based on imidazolium ionic liquids (ILs), including polymerizable
      surfactant ILs, have been synthesized and used to stabilize polymerizable
      microemulsions useful for producing polymer nanoparticles, gels, and open-cell
      porous materials.

PMID- 16786092
TI  - Reactivity of electrophilic micro-phosphinidene complexes with N-heterocyclic
      carbenes: formation of the first main group element adducts of 'abnormal' carbene
      ligands.
AB  - The reactions of Mn2- and Co2-containing micro-PNiPr2 complexes with NCN carbenes
      afford the 'abnormal' carbene adducts [Mn2(CO)8{mu-P(NiPr2)}(4-cyclo-C3H2-1,3
      (NR)2))] and [Co2(CO)4(mu-dppm){mu-P(NiPr2)(4-cyclo-C3H2-1,3-(NR)2)}] (R = tBu,
      adamantyl), respectively.

PMID- 16786093
TI  - A tryptophan-containing fluoroionophore sensor with high sensitivity to and
      selectivity for lead ion in water.
AB  - We report herein a fluoroionophore sensor derivated from tryptophan that shows
      high sensitivity (detection limit up to 0.15 microM) and specific selectivity for
      lead ion (Pb2+) over Ca2+, Cd2+, Co2+, Cr3+, Cu2+, K+, Mg2+, Na+, Fe2+, Mn2+,
      Ni2+ and Zn2+ in aqueous solution.

PMID- 16786094
TI  - Switching in molecular shapes: main chain length driven rod-circle transition of
      isolated helical polysilanes.
AB  - Unique conformations such as rod, semicircle, and circle structures of isolated
      semi-flexible helical polysilanes were observed by atomic force microscopy (AFM);
      the chain topology was significantly related to the chain length (molecular
      weight) on the surfaces.

PMID- 16786095
TI  - Highly-regulated nanocoatings of polymer films on carbon nanofibers using
      ultrasonic irradiation.
AB  - It was demonstrated that nanoprecise coatings of uniform and densely packed
      polymer layers on nanomaterials and uniform polymer coatings on individual nano
      objects are formed using ultrasonic effects.

PMID- 16786096
TI  - Direct conversion of esters, lactones, and carboxylic acids to oxazolines
      catalyzed by a tetranuclear zinc cluster.
AB  - The tetranuclear zinc cluster Zn4(OCOCF3)6O catalyzes the direct conversion of
      esters, lactones, and carboxylic acids to oxazolines with remarkable
      chemoselectivity.

PMID- 16786097
TI  - Vibrational circular dichroism and ab initio structure elucidation of an aromatic
      foldamer.
AB  - Ab initio calculations together with vibrational circular dichroism (VCD) are
      validated as very accurate tools for studying conformations and estimating
      conformational energies and helical handedness preferences of an entire, large
      (112 atoms), abiotic foldamer.

PMID- 16786098
TI  - An ordered cubic Im3m mesoporous Cr-TiO2 visible light photocatalyst.
AB  - An ordered and well-crystallized cubic Im3m mesoporous Cr-TiO2 photocatalyst with
      superb performance under visible light has been fabricated.

PMID- 16786099
TI  - An efficient total synthesis and absolute configuration determination of
      varitriol.
AB  - The first total synthesis and the absolute configuration determination of
      varitriol are described.

PMID- 16786100
TI  - Acellular pertussis vaccine for adolescents.
AB  - BACKGROUND: The use of whole-cell pertussis vaccine has led to a significant
      decline in incidence of the disease among children. This change in the
      epidemiological profile led to an increased number of cases among teenagers and
      adults, as a result of loss of immunity to the disease or vaccine after
      approximately 10 years. An increased number of cases was also observed among non
      immunized or partially immunized infants. Licensure of the DTP vaccine against
      diphtheria, tetanus, and acellular pertussis formulated specifically for patients
      over 10 years of age (Tdap) suggests the possibility of controlling pertussis in
      the most affected age groups over the past few years. SOURCES OF DATA: Data were
      collected from MEDLINE. The research was limited to the period between January
      1995 and January 2006. SUMMARY OF THE FINDINGS: In some countries there are two
      Tdap vaccines licensed for patients over 10 years of age. One of them contains
      five immunogenic components of Bordetella pertussis (pertussis toxin, filamentous
      hemagglutinin, fimbriae 2 and 3, and pertactin), and the other contains three
      components (pertactin, filamentous hemagglutinin, and inactivated pertussis
      toxin), the latter being the only one licensed in Brazil up to now. Although the
      composition of the two vaccines differs, studies show that they have similar
      effectiveness and immunogenicity. Some authors, however, emphasize that it is
      difficult to make a precise assessment of the immunological response to the
      vaccine and its duration. Several countries currently recommend the use of Tdap
      vaccine for adolescents. Canada has extended the target population up to 54 years
      of age. The guideline is that this group should receive one dose of the vaccine
      to reinforce the basic immunization scheme. This is based on study results that
      show that the vaccine-induced immunity lasts for around 6 to 12 years.
      Assessments of the economic impact of routine use of the vaccine in adolescents
      showed a positive cost-benefit ratio. Results of the epidemiological impact
      depend on the quality of diagnosis so that data reflect the reality of the
      disease. CONCLUSIONS: Although some questions remain to be clarified, the
      literature indicates the possibility of solving the "reappearance" of whooping
      cough (pertussis) with the use of Tdap vaccine. Perhaps the strategy of using a
      second booster dose in adolescence to replace the double diphtheria and tetanus
      vaccine should be adopted immediately.

PMID- 16786101
TI  - Vaccines against rotavirus and human papillomavirus (HPV).
AB  - OBJECTIVE: To briefly review strategies aimed at the development of rotavirus and
      HPV vaccines, with emphasis on the current status of studies assessing the
      safety, reactogenicity, immunogenicity and efficacy of recently developed
      vaccines. SOURCES OF DATA: This review focuses on articles published from 1996 to
      2006, mainly those from the last five years, with special emphasis on data
      obtained from recently completed studies involving a new live attenuated human
      rotavirus vaccine and a virus-like particle (HPV) vaccine. SUMMARY OF THE
      FINDINGS: Strategies for developing rotavirus vaccines ranged from Jennerian
      approaches to the new human-derived rotavirus vaccine. Currently, two rotavirus
      vaccines are recognized as both efficacious and safe: a pentavalent human-bovine
      reassortant vaccine and a vaccine derived from an attenuated rotavirus of human
      origin. The second of these has been evaluated in more than 70,000 infants all
      over the world. Prophylactic vaccines against HPV have been tested in more than
      25,000 young individuals around the world. Results from phase II and III clinical
      studies indicate that such vaccines against the most common types of HPV, those
      linked to both genital warts and 70% of cervical cancers, are safe and highly
      efficacious. CONCLUSIONS: A future rotavirus immunization program covering 60 to
      80% of infants worldwide is likely to reduce by at least 50% the number of
      rotavirus-associated hospitalizations and deaths. It is also reasonable to expect
      that implementation of HPV prophylactic vaccines will reduce the burden of the
      HPV-related diseases that presently impact millions of people around the world.

PMID- 16786102
TI  - Effect of adrenomedullin on the activity of barosensitive neurons in the rostral
      ventrolateral medulla of rats.
AB  - To investigate the eletrophysiological effect of rat adrenomedullin (rADM) on
      barosensitive neurons in the rostral ventrolateral medulla (rVLM) and its
      potential mechanisms, the extracellular recording and multi-barrel iontophoresis
      methods were used. Of the 29 barosensitive neurons in the rVLM, 20 neurons
      demonstrated excitatory response to iontophoretically applied rADM and increased
      the firing rate from (10.8 +/- 2.7) spikes/s to (14.6 +/- 3.6), (19.8 +/- 4.7)
      and (31.9 +/- 6.4) spikes/s (P<0.05, n=20) at the current of 30, 60 and 90 nA,
      respectively. Application of human adrenomedullin (22-52) [hADM (22-52)], a
      specific antagonist of rADM receptor, distinctly attenuated the augmentation of
      firing rate induced by rADMjthe firing rate was increased by 15.4% [(11.4 +/-
      2.5) spikes/s, P<0.05, n=10]. Another antagonist, human calcitonin gene-related
      peptide (8-37) [hCGRP (8-37)] had no significant effect on rADM-induced
      excitation. Other 23 barosensitive neurons were recorded to test the influence of
      nitric oxide synthase (NOS) inhibitors on the excitatory effect of rADM. In 10
      neurons, 7-NiNa (neuronal NOS inhibitor) decreased the firing rate from (10.1 +/-
      3.5) spikes/s to (7.5 +/- 2.5), (5.3 +/- 2.1) and (3.1 +/- 1.4) spikes/s (P<0.05,
      n=10) at the current of 10, 20 and 40 nA, respectively. The excitatory effect of
      rADM (60 nA, 30 s) during 7-NiNa application was nearly eliminated and the
      magnitude of firing rate was increased only by 17% of the basal level (6.2 +/-
      1.9) spikes/s (P<0.05, n=7). While aminoguanidine (AG, iNOS inhibitor) increased
      the firing rate at the resting level from (11.5 +/- 5.1) spikes/s to (17.8 +/-
      5.6), (22.5 +/- 6.3) and (29.1 +/- 6.4) spikes/s (P<0.05, n=8) at the current of
      10, 20 and 40 nA in 8 barosensitive neurons, respectively. When rADM (60 nA, 30
      s) was delivered during AG iontophoresis period, the firing rate significantly
      increased by 60% of the basal level [(22.5 +/- 6.3) spikes/s, n=5]. These results
      indicate that rADM activates the barosensitive neurons in the rVLM directly and
      acts as a cardiovascular regulator, and that this function might be mediated by
      its specific receptor. NO, mainly neuronal NOS-originated might be involved in
      the excitatory effect of rADM in the rVLM.

PMID- 16786103
TI  - [Protective effect of sevoflurane preconditioning on oxygen-glucose deprivation
      injury in rat hippocampal slices: the role of mitochondrial K(ATP) channels].
AB  - To investigate the neuroprotective effects of sevoflurane preconditioning on
      oxygen-glucose deprivation (OGD) injury and the role of mitochondrial KATP
      channels in rat, we established OGD injury model in rat hippocampal slices. The
      brain was rapidly removed, and the dissected hippocampus was sliced in cold
      artificial cerebrospinal fluid (ACSF) transversely to its longitudinal axis (400
      mum thick) with a Rotorslicer DTY-7700. Slices were placed on a nylon mesh in a
      recording chamber at 34 degrees C and humidified gas mixture (95% O2/5% CO2) was
      applied to the chamber at a flow rate of 200 ml/min. After 2 h of incubation,
      slices were randomly exposed to 2%, 4%, 6% sevoflurane or 6% sevoflurane combined
      with mitochondrial K(ATP) channel blocker (5-hydroxydecanoic acid, 5-HD) under
      normal condition (95% O2/5% CO2) for 30 min. Fifteen minutes later, slices were
      exposed to 14-minute OGD followed by 1-hour reoxygenation, and the changes of
      orthodromic population spike (OPS) at the end of reoxygenation were measured. The
      changes of ultrastructure of CA1 area in the group of 14-minute OGD followed by 1
      hour reoxygenation were detected with electron microscope. The results showed
      that sevoflurane preconditioning delayed the abolishing time of OPS (P<0.01) and
      significantly increased the recovery rate and the recovery amplitude of OPS
      compared with the OGD group. The recovery rate of OPS was 71.4% both in 4% and 6%
      sevoflurane preconditioning groups (P<0.05 vs OGD group), accordingly the
      recovery amplitude of OPS was (61.0 +/- 42.3)% and (78.7 +/- 21.1)% (P<0.01),
      respectively. The protective effect of 6% sevoflurane was blocked by 5-HD.
      Ultrastructural observation in the hippocampal CA1 region of the OGD group showed
      severe edema of the pyramidal cells, crimpled or ruptured nucleus membranes,
      aggregation of chromatin, and swelling of mitochondria, whereas these changes
      were less prominent in 4% and 6% sevoflurane groups. These results suggest that
      sevoflurane preconditioning is capable to protect neurons from OGD injury in
      vitro and that the protective effect is related to the activation of
      mitochondrial K(ATP) channels.

PMID- 16786104
TI  - [Rac1 accelerates endothelial cell senescence induced by hypoxia in vitro].
AB  - To investigate the role and mechanism of Rac1 protein in the process of the human
      umbilical vein endothelial cell (HUVEC) senescence, we used hypoxia as a model
      for modulating HUVECs entering replicative senescence in vitro. Premature
      senescence of HUVECs was evidenced by detecting the SA-beta-Gal activity and PAI
      1 expression. Meanwhile, cell cycle distribution and cell proliferation rate were
      investigated by flow cytometry assay and BrdU staining. The results indicated
      that the HUVECs became enlarged and flattened, both SA-beta-Gal activity and PAI
      1 expression increased obviously, while cell proliferation was inhibited and G(1)
      phase cell cycle arresting occurred when HUVECs were treated with continued
      hypoxia for 96 h. Accompanied with these changes, the expression of activated
      Rac1 increased obviously in cells after hypoxia. All these observations suggested
      that endothelial senescence could be induced by continued hypoxia and it might
      correlate with the activity of Rac1. To further define the relationship between
      Rac1 and HUVEC senescence, HUVECs were transiently infected with the
      constitutively active form of Rac1 (V12Rac1) or dominant negative form of Rac1
      (N17Rac1) using retrovirus vector pLNCX-V12Rac1 or pLNCX-N17Rac1. We observed the
      changes of these three kinds of HUVECs (HUVECs, N17Rac1-HUVECs, V12Rac1-HUVECs)
      after hypoxia for 48 h and 96 h, the expression and localization of serum
      response factor (SRF), which is one of the downstream signal molecules of Rac1,
      were also investigated. The results obtained indicated that after continued
      hypoxia for 48 h, HUVECs infected by V12Rac1 showed obvious senescence
      accompanied with SA-beta-Gal activation, PAI-1 expression increase, G(1) phase
      arrest and cell proliferation inhibition which were similar to HUVECs after
      continued 96-hour hypoxia treatment, while the senescence of HUVECs infected by
      N17Rac1 was significantly inhibited even if the cells were exposed to hypoxia for
      more than 96 h. All the results identified that the activation of Rac1 might
      accelerate HUVEC senescence induced by hypoxia and that inactivation of Rac1
      could partly block the cell senescence. To further investigate the mechanism of
      HUVEC senescence induced by Rac1, we detected the expression of total SRF (tSRF)
      and nuclear SRF (nSRF) in these three kinds of HUVECs by immunofluorescent
      analysis and Western blot assay after hypoxia. The results showed that the
      expression of nSRF decreased obviously and the nuclear translocation of SRF was
      inhibited in HUVECs infected by V12Rac1 compared with those in the normal HUVECs.
      In contrast, the expression of nSRF increased obviously in the HUVECs infected by
      N17Rac1. These results suggest that activation of Rac1 accelerates endothelial
      cell senescence and inhibition of Rac1 activity prevents HUVECs from entering
      senescence induced by hypoxia, while the nuclear translocation of SRF regulated
      by Rac1 might play an important role in the process of senescence.

PMID- 16786105
TI  - Identification and function of the growth hormone gene in Rongjiang pig of China.
AB  - Growth of animal is largely regulated by growth hormone (GH). In this study, the
      GH gene was isolated and cloned from the genomic DNA library from Rongjiang pig,
      a Chinese local swine, using polymerase chain reaction technique. The complete
      nucleotide sequence of a 1.903 kb genomic fragment containing Rongjiang swine GH
      gene has been determined. The GH gene contained five exons and four introns
      similar to the GH genes of other mammalians and exhibited 97%~99% identity to the
      GH genes of the four western meat-type breeds and nine Chinese local pigs.
      Polymorphism of GH genes was analyzed by using the restriction enzymes Dde I, Nar
      I and BsmN I in four western meat-type breeds and ten Chinese local pigs. Five
      polymorphic restriction sites, with Dde I at the base 622 (G/A) in exon 2 and 274
      (T/C) in 5o-flank, with Nar I at 631 (G/A) in exon 2, and with BsmN I at the base
      841 (T/C) in intron 2 and 1358 (A/G) in exon 4, were identified. The polymorphic
      restriction site at 1358 (A/G) leaded to the GH mature protein of Rongjiang pig
      differing from that of four western meat-type breeds and eight Chinese local
      breeds at the residue Val108 substituted by Ile108. According to the crystal
      structure of human GH mature protein, this Ile108 substitution might result in a
      lower affinity of GH for its receptor in Rongjiang breed.

PMID- 16786106
TI  - [Effects of neuropeptide Y on ion channels in ventricular myocytes].
AB  - Neuropeptide Y (NPY) co-exists with norepinephrine (NE) in sympathetic terminals,
      and is the most abundant neuropeptide in myocardium. Many studies have focused on
      the effects of NE on ion channels in cardiac myocytes and its physiological
      significance has been elucidated relatively profoundly. There have been few
      investigations, however, on the physiological significance of NPY in myocardium.
      The effects of NPY on L-type Ca2+ channel currents (I(Ca-L)) were evaluated in
      some studies and different results were presented, which might be attributed to
      the different species of animal tested and different methods used. It is
      necessary, therefore, to study the effects of NPY on ion channels in cardiac
      myocytes systematically and further to discuss the biological significance of
      their coexistence with NE in sympathetic terminals. The single ventricular
      myocytes from adult rat or guinea pig (only for measuring I(K)) were prepared
      using enzymatic dispersion. I(Ca-L), I(to), I(Na/Ca), I(Na) and I(K) in the
      cellular membrane were observed using whole cell voltage-clamp recording. In the
      present study, NPY from 1.0 to 100 nmol/L dose-dependently inhibited I(Ca-L)
      (P<0.01, n=5). The maximal rate of inhibition in this study reached 39% and
      IC(50) was 1.86 nmol/L. NPY had no effect on the voltage-dependence of calcium
      current amplitude and on the voltage-dependence of the steady-state gating
      variables. I(Ca-L) was activated at -30 mV, reaching the maximum at 0 mV. When
      both NE and NPY were applied with a concentration ratio of 500:1, 10 nmol/L NPY
      inhibited I(Ca-L) that had been increased by 5 mumol/L NE, which was consistent
      with the effect of NPY only on I(Ca-L). NPY also inhibited I(Na/Ca). At a
      concentration of 10 nmol/L, NPY inhibited inward and outward I(Na/Ca) from
      (0.27+/-0.11) pA/pF and (0.45+/-0.12) pA/pF to (0.06+/-0.01) pA/pF and (0.27+/
      0.09) pA/pF, respectively (P<0.05, n=4). NPY at 10 nmol/L increased I(to) from
      (12.5+/-0.70) pA/pF to (14.7+/-0.59) pA/pF(P<0.05, n=4). NPY at 10 nmol/L did not
      affect I(Na) in rat myocytes and I(K) in guinea pig myocytes. NPY increased the
      speed of action potential depolarization and reduced action potential duration of
      I(Ca-L), I(Na/Ca) and I(to), which contributed to the reduction of contraction.
      These results indicate that the effects of NPY are opposite to the effects of NE
      on ion channels of cardiac myocytes.

PMID- 16786107
TI  - The electrophysiological properties of HVC-RA synaptic transmission in the adult
      zebra finch in vivo.
AB  - The synaptic connection from high vocal center (HVC) to robust nucleus of the
      arcopallium (RA) is a pivotal part of vocal motor pathway in songbirds.
      Electrophysiological properties of HVC-RA synaptic transmission in adult male
      zebra finch (Taeniopygia guttata) in vivo was investigated by using field
      potential recording method. Following electrical stimulation of HVC, the evoked
      field potentials recorded in RA were feeble. The results showed that the
      remarkable paired-pulse facilitation was induced by paired-pulse stimulation at
      HVC-RA synapses. The results also showed that the evoked field potentials were
      significantly decreased after a conditioning tetanic stimulation and finally
      recovered gradually within 15 min, which indicates tetanic stimulation-induced
      transient depression is present at HVC-RA synaptic transmission. These results
      suggest that properties of synaptic transmission in this pathway might play a
      role in controlling song production.

PMID- 16786108
TI  - Effects of gastric ischemia-reperfusion on gastric mucosal cellular apoptosis and
      proliferation in rats.
AB  - The effect of gastric ischemia-reperfusion (GI-R) on gastric mucosal cellular
      apoptosis and proliferation was investigated using histological,
      immunohistochemical methods in Sprague-Dawley rats. The GI-R model was
      established by clamping the celiac artery for 30 min and reperfusing for 0, 0.5,
      1, 3, 6, 24, 48, 72 h, respectively. Mild gastric mucosal injury was induced by
      ischemia alone. However, the injury worsened and reached the maximum at 1 h after
      reperfusion, almost simultaneously with the gastric mucosal cellular apoptosis
      increase and cellular proliferation decrease in gastric mucosa. Then, gastric
      mucosal cells began to repair by increasing gastric cellular proliferation, which
      achieved the maximum at 24 h after reperfusion. The mucosal lesions were almost
      completely repaired at about 72 h after reperfusion. These results indicate that
      the gastric mucosal injury after GI-R is mainly induced by reperfusion. The
      damaged gastric mucosa could initiate its repairing mechanism immediately through
      inhibiting cellular apoptosis and increasing the number of proliferative cells,
      which substitute the damaged cells gradually. The plerosis almost completes in
      three days after reperfusion showing a strong self-repair ability of gastric
      mucosa.

PMID- 16786109
TI  - Cigarette smoke extract inhibits the proliferation of alveolar epithelial cells
      and induces apoptosis.
AB  - Cigarette smoke extract (CSE) contains abundant oxidants and free radicals.
      Oxidative stress caused by cigarette smoking results in the destruction of the
      alveolar cell walls and emphysema. However, there exists discrepancy about how
      CSE works in the process. In the present study, we observed the effect of CSE on
      the cell growth of type II alveolar epithelial cell-derived A549 cell line, and
      provided molecular understanding of this effect. The MTT assay results showed
      that CSE decreased the cell viability of A549 cells in a dose- and time-dependent
      manner, and cell cycle was arrested in G(1)/S phase. Furthermore, CSE-induced
      apoptosis of A549 cells was verified by Hoechst 33258 staining, electron
      microscopy in morphology, and the appearance of DNA fragmentation and annexin V
      FITC/propidium iodide (PI) staining assay at molecular level. It was found that
      CSE treatment resulted in the upregulation of Fas/APO-1 receptor and activation
      of caspase-3. CSE also initiated accumulation of intracellular reactive oxygen
      species, which was detected by laser confocal microscopy. Taken together, CSE
      could inhibit the cell growth and induce apoptosis of A549 cells through Fas
      receptor pathway. Oxidative stress caused by CSE may be the radical factor
      leading to apoptosis as well as cell growth inhibition in alveolar epithelial
      cells.

PMID- 16786110
TI  - [Dynamic changes of adenomatous polyposis coli protein and glycogen synthase
      kinase 3beta in the repair of the injured airway epithelial cells in smoking
      mice].
AB  - To investigate the roles of adenomatous polyposis coli (APC) protein and glycogen
      synthase kinase 3beta (GSK3beta) of smoking murine model in the repair of the
      injured airway epithelial cells (AECs) in different stages, 30 male Kun-Ming mice
      were randomly divided into two groups, the control group and the smoking group.
      There were 24 mice in smoking group, and 6 animals were separately killed at the
      end of the 1st, 4th, 8th and 12th week after smoking. Then the following tests
      were undertaken: (1) HE staining of lung section to observe the morphological
      changes of the bronchi in the smoking mice. (2) Immunohistochemical staining of
      APC protein and GSK3beta in the AECs. (3) Western blot was used to detect the
      levels of APC protein, GSK3beta and phosphorated GSK3beta (p-GSK3beta) in
      pulmonary tissue. (4) Observing the localizations of APC protein and GSK3beta in
      the AECs by immunofluorescence technique. The results showed: (1) AECs showed
      changes of predominant injury (1-, 4-week), repair (8-week) and reinjury (12
      week) along with smoking time prolonged. The experimental results indicated that
      the model of smoking mice was duplicated successfully. (2) Immunohistochemical
      results showed that the expression of APC protein in the AECs increased after 1
      week smoking (0.458 +/- 0.062 vs 0.399 +/- 0.060, P< 0.05 vs control), but was
      significantly decreased at the end of the 4th week (0.339+/- 0.056, P<0.01 vs
      control) and increased at the end of the 8th and 12th week (0.387 +/- 0.041,
      0.378 +/- 0.037, P<0.05 vs 4-week). The expression of GSK3beta in the AECs of
      smoking mice obviously decreased (P<0.01 or P<0.05 vs control). (3) Western blot
      showed that the expressions of APC protein and GSK3beta in lung tissue were
      consistent with the results of immunohistochemistry; and the levels of p-GSK3beta
      in all smoking models were higher than that in control. (4) The results of
      immunofluorescence showed that APC protein was localized mainly near the regions
      of epithelial cell membrane at the end of the 1st and 8th week after smoking,
      which were dissimilar with the localization in control, and this change was not
      seen in the location of GSK3beta. Taken together, these results demonstrate that
      the expressions and localizations of APC protein, GSK3beta and the activity of
      GSK3beta are dynamically changed in the AECs with experimental smoking injury at
      different phases, suggesting that APC protein and GSK3beta may be involved in the
      regulation of migration and proliferation of AECs, and play an important role in
      the process of repair of airway epithelium injury.

PMID- 16786111
TI  - [Effect of opening of mitochondrial ATP-sensitive K+ channel on the distribution
      of cytochrome C and on proliferation of human pulmonary arterial smooth muscle
      cells in hypoxia].
AB  - The objective of this paper was to investigate the contribution of mitochondrial
      ATP-sensitive K+ channel (mitoK(ATP)) and mitochondrial membrane potential
      (Deltapsim) to the distribution of cytochrome C in human pulmonary arterial
      smooth muscle cells (HPASMCs) and to the proliferation of HPASMCs induced by
      hypoxia. HPASMCs were divided into 6 groups, as following: (1) control group:
      cultured under normoxia; (2) diazoxide group: cultured in normoxia with
      diazoxide, an opener of mitoK(ATP); (3) 5-HD group: cultured in normoxia with 5
      hydroxydecanoate (5-HD), an antagonist of mitoK(ATP); (4) 24-hour hypoxia group:
      cultured in hypoxia for 24 h; (5) 24-hour hypoxia + diazoxide group: cultured in
      hypoxia with diazoxide for 24 h; (6) 24-hour hypoxia + 5-HD group: cultured in
      hypoxia with 5-HD for 24 h. The relative changes in mitochondrial potential were
      tested with rhodamine fluorescence (R-123) technique. Western blot was used to
      detect the expression of cytochrome C protein in cell plasma and
      mitochondria,respectively. The expression of cell caspase-9 protein was
      determined with Western blot. The proliferation of HPASMCs was examined by cell
      cycle analysis and MTT colorimetric assay. The results were as following: after
      exposure to diazoxide for 24 h, the intensity of R-123 fluorescence in normoxic
      HPASMCs was significantly increased compared with that in the control group
      (P<0.05), but there was no significant change of the intensity of R-123
      fluorescence after the HPASMCs had been exposed to 5-HD for 24 h; 24-hour hypoxia
      or 24-hour hypoxia + diazoxide could markedly increase the intensity of R-123
      fluorescence in HPASMCs compared with normoxia (P<0.05), and the change was more
      significant in 24-hour hypoxia + diazoxide group than that in 24-hour hypoxia
      group (P<0.05); 5-HD could weaken the effect of 24-hour hypoxia on the intensity
      of R-123 fluorescence. After exposure to diazoxide for 24 h, the ratio of the
      expression of cytosolic cytochrome C protein to that of mitochondrial cytochrome
      C protein was significantly decreased compared with that in the control group
      (P<0.05), and the expression of caspase-9 protein was significantly decreased
      compared with that in the control group (P<0.05). The percentage of S phase and A
      value of MTT were significantly increased compared with those in the control
      group (P<0.05). But there were no significant changes in these tests after
      HPASMCs had been exposed to 5-HD for 24 h (P>0.05). After exposure to hypoxia or
      hypoxia + diazoxide for 24 h, the ratio of the expression of cytosolic cytochrome
      C protein to that of mitochondrial cytochrome C protein and the expression of
      caspase-9 protein were significantly decreased compared with those in the control
      group (P<0.05). The percentage of S phase and A value of MTT were significantly
      increased compared with those in the control group (P<0.05). These changes were
      more significant in 24-hour hypoxia + diazoxide group than those in 24-hour
      hypoxia group (P<0.05). 5-HD could weaken the effect of hypoxia on the changes of
      the distribution of cytochrome C, the expression of caspase-9 in HPASMCs and the
      proliferation of HPASMCs induced by hypoxia (P<0.05). All these results suggest
      that the opening of mitoK(ATP) followed by a depolarization of Deltapsim induced
      by hypoxia might contribute to the inhibition of the release of cytochrome C from
      mitochondria to plasma in HPASMCs. This might be a mechanism of the development
      of hypoxic pulmonary hypertension. The signal transduction pathway of
      mitochondria might play an important role in the relationship between Deltapsim
      and apoptosis of HPASMCs.

PMID- 16786112
TI  - [Protein kinase Cdelta is possibly involved in the transition from hypertrophy to
      apoptosis of myocardiocytes].
AB  - Cardiac hypertrophy is an adaptive process to an increased hemodynamic overload.
      However, the adaption may lead to the fragility of myocardium facing pathological
      stimuli. In the present study, experiments were designed to explore the
      susceptibility of hypertrophic myocardiocytes to apoptotic stimuli and the role
      of protein kinase Cdelta (PKCdelta) during the transition from hypertrophy to
      apoptosis. Endothelin-1 (ET-1)-treated cardiomyocytes were used as model of
      cardiac hypertrophy. Angiotensin II (Ang II) was used as an apoptotic stimulus.
      Cell surface area was measured to determine the extent of hypertrophy. The
      apoptotic rate in cardiomyocytes was detected by Hoechst 33258. (1) Cell surface
      area was increased by 42.5% and 67.3% following 1 nmol/L and 10 nmol/L ET-1
      treatment, respectively, as compared with serum-free cultured myocytes. So the
      mildly and moderately hypertrophic myocyte models were set up. (2) Apoptotic
      rates in serum-free cultured, mildly and moderately hypertrophic myocytes after
      Ang II treatment were (15.54+/-1.32) %, (20.65+/-1.40) % and (29.33+/-3.52) %,
      respectively. It is suggested that hypertrophic myocytes are more susceptive to
      apoptotic stimulus. (3) Rottlerin, a specific inhibitor of PKCdelta depressed
      apoptotic rates induced by Ang II to (15.88+/-2.25) % in mildly hypertrophic
      myocytes and to (15.01+/-1.37) % in moderately hypertrophic myocytes; but
      rottlerin did not affect apoptotic rate induced by Ang II in serum-free cultured
      myocytes. These results suggest that inhibition of PKCdelta can reduce Ang II
      induced apoptosis of hypertrophic cardiomyocytes and that PKCdelta is possibly
      involved in the apoptotic process of hypertrophic cardiomyocytes.

PMID- 16786113
TI  - Regulative effects of ovarian steroids on rat gastric motility and sensitivity.
AB  - Women often complain gut symptoms during pregnancy and the luteal phase of the
      menstrual cycle. To investigate the relationship between ovarian steroids and the
      abnormal gut motility and sensitivity, the expressions of cholecystokinin (CCK),
      calcitonin gene-related peptide (CGRP) and their receptors in stomach were
      studied in ovariectomized rats. Blood samples were collected for estradiol
      (E(2)), progesterone (P(4)), CCK and CGRP radioimmunoassay. Expression of CCK(A)
      receptor in fundus was assessed by Western blot and CGRP receptor was determined
      by (125)I-CGRP radioligand binding assay (RBA). The replacement therapy with
      estradiol benzoate (EB) could dose-dependently increase the plasma CCK level and
      the expression of gastric CCK(A) receptor (P<0.05 respectively). P(4) replacement
      therapy could stimulate the release of CGRP and increase the binding sites of
      CGRP receptors in stomach (P<0.05 respectively). The combined effect of EB and
      P(4) was to stimulate the release of CCK and CGRP, and to increase the
      expressions of gastric CCK(A) and CGRP receptors. These results indicate that EB
      could inhibit gastric emptying by increasing CCK secretion and CCK(A) receptor
      expression in ovariectomized rats. P(4) could increase gut sensitivity by up
      regulating the release of CGRP and the activity of CGRP receptor. It could be
      deduced from these observations that CCK(A) and CGRP receptor antagonists could
      be used for female patients who suffer from gastrointestinal dysfunction closely
      related with the menstrual cycle, such as distension, satiety, bloating and
      abdominal pain.

PMID- 16786114
TI  - [Delayed disappearance of h-VEGF165 mRNA and protein under regulation of hypoxic
      response element].
AB  - Transfer of vascular endothelial growth factor (VEGF) gene to ischemic myocardium
      may provide a useful approach for angiogenesis and improve cardiac performance.
      However, uncontrolled expression of VEGF in vivo may result in certain side
      effects, such as hemangioma formation, retinopathy, and tumor development. We
      investigated the feasibility of using the nine copies of hypoxic response element
      (HRE) to control the expression of human VEGF(165) (h-VEGF(165)) under anoxic
      condition at cell level and also observed the synchron of h-VEGF(165) mRNA and
      protein expressions. Recombinant adeno-associated viral (rAAV) vector was
      prepared by using the three-plasmid system and cotransfected to human embryo
      kidney 293T cells by the calcium phosphate precipitates method. The rAAV vector
      was purified by chloroform-PEG8000/NaCl-chloroform and added to cultured
      myocardiocytes. Myocardiocytes of Sprague-Dawley rat were cultured in serum-free
      medium and then randomly divided into eight groups. Group I: cultured under
      normoxic conditions (21% O2) for 8 h as control; Group II: cultured under anoxic
      conditions (1% O2) for 8 h; Group III: cultured under normoxic conditions (21%
      O2) for 8 h with gene transfer; Group IV: cultured under anoxic conditions (1%
      O2) for 8 h with gene transfer; Group V, VI, VII: cultured under anoxic
      conditions (1% O2) for 8 h with gene transfer and then tured to normoxic
      conditions (21% O2) for 4, 8 or 12 h, respectively; Group VIII: cultured under
      anoxic conditions (1% O2) for 20 h with gene transfer. After completion of cell
      culture, the amount of h-VEGF(165) protein in culture supernatant was quantified
      by using enzyme linked immunosorbent assay (ELISA). Expression of h-VEGF(165)
      protein in cultured cardiacmyocytes was also evaluated by immunofluorescence. RT
      PCR was employed to detect the expression of h-VEGF(165) mRNA. The results
      revealed that there were no expressions of h-VEGF(165) mRNA and protein in groups
      I, II, III, VI and VII. After gene transfer, the expressions of h-VEGF(165)
      protein and mRNA were significantly higher in groups IV and VIII than those in
      other groups (P<0.01); Immunofluorescence positive cells were observed in groups
      IV, V and VIII. RT-PCR revealed that a 484-bp strip can be found in groups IV and
      VIII, but unavailable in other groups. We conclude that HRE is a promising
      regulator for h-VEGF(165) gene expression following the changes of oxygen
      environment. HRE can induce the expression of h-VEGF(165) gene after hypoxia, but
      in normal oxygen condition, the expression of h-VEGF(165) was inhibited. Although
      expression of h-VEGF(165) mRNA ceased in normal oxygen condition under the
      control of HRE, expression of h-VEGF(165) protein was hysteretic to h-VEGF(165)
      mRNA expression.

PMID- 16786115
TI  - The tetanus patterns for the induction of long-term depression in the adult rat
      hippocampus.
AB  - Previous reports suggested that a low-frequency stimulus (LFS) of 1~2 Hz (600~900
      pulses) induced a homosynaptic long-term depression (LTD) of synaptic efficacy in
      the hippocampal CA1 area of young rats (< 4-week old). However, these stimulation
      protocols often failed to induce LTD in the adult CA1 hippocampus. In the present
      study, we examined the effects of two novel tetanus patterns on LTD induction in
      adult rat hippocampal slices. We determined that these novel stimulation
      protocols induced LTD in the adult hippocampus, and that the characteristics of
      induced LTD were parameter-specific, including latency (period from the end of
      tetanus to a beginning of LTD) and the amplitude of LTD. These results suggest
      that LFS with certain patterns can induce LTD in the CA1 area of adult rat
      hippocampal slices, and that the multi-trains of 2-Hz protocol provided more
      effective response than the 5-Hz protocol.

PMID- 16786116
TI  - Expression of vascular endothelial growth factor receptors is closely related to
      the histological grade of hepatocellular carcinoma.
AB  - Angiogenesis is important for tumor growth, and is regulated by angiogenetic
      factors such as vascular endothelial growth factor (VEGF). In the present study,
      we investigated whether or not expression of VEGF receptors (VEGFRs) is related
      to the proliferation of tumor cells in hepatocellular carcinoma (HCC). We
      simultaneously stained proliferation marker Ki-67 antigen and either VEGFR1 (Flt
      1) or VEGFR2 (Flk-1) on paraffin-embedded tissue sections from 50 cases of
      surgically resected human HCC. Based on the staining pattern of VEGFRs, we
      classified the cases into 4 categories; receptor double-negative, Flt-1 single
      positive, Flk-1 single-positive, receptor double-positive. Interestingly, the Ki
      67 index was significantly lower in receptor double-negative cases in comparison
      to that in either Flt-1 single-positive or Flk-1 single-positive cases (P =
      0.0491, P = 0.0196, respectively). Moreover, the index was also significantly
      lower in receptor double-positive cases in comparison to either Flt-1 single
      positive or Flk-1 single-positive cases (P = 0.0026, P < 0.0001, respectively).
      We further investigated 35 cases showing a Ki67 index > 10% to determine the
      expression of VEGFRs on Ki-67 antigen-positive proliferating cells. Surprisingly,
      the histological grade of HCC and the expression pattern of VEGFRs showed a
      characteristic relation; the well-differentiated HCC cases were all distributed
      in the Flk-1-positive group (7/7), moderately differentiated HCC cases were
      distributed in either the Flt-1 or Flk-1 single-positive group (20/21), and
      poorly differentiated HCC cases were predominantly distributed in either the
      receptor double-negative or double-positive group (6/7). These findings suggest
      that the expression pattern of VEGFRs influences the histological differentiation
      of HCC.

PMID- 16786117
TI  - Clinicopathologic and genetic characteristics of gastric cancer in young male and
      female patients.
AB  - The pathways of gastric cancer in young patients (40 years of age or younger)
      have not yet been determined. We therefore examined clinicopathologically and
      genetically 68 gastric cancers in young patients and 66 tumors in older patients
      (41 years of age or older). Mutations in B-raf and K-ras were identified by PCR
      SSCP following sequencing. Microsatellite instability (MSI) and hMLH3 mutations
      were also examined. Histopathologically, diffuse-type gastric cancer and cancer
      in the whole of the stomach were found significantly more often in young patients
      than in older patients (21% vs. 2%, P = 0.0006, and 77% vs. 32%, P < 0.0001,
      respectively). Genetically, MSI and hMLH3 mutations were found significantly more
      often in tumors in young patients than in tumors in older patients (15% vs. 4%, P
      = 0.040, and 9% vs. 0%, P = 0.036, respectively). Tumors in young female patients
      were found significantly less often in the lower-third of the stomach and showed
      a significantly greater frequency of MSI, compared to tumors in young male
      patients (33% vs. 9%, P = 0.046, 5% vs. 30%, P = 0.010, respectively). These
      results suggest that the pathways of gastric carcinogenesis differ between young
      patients and older patients, and that the pathways differ between the sexes in
      young patients.

PMID- 16786118
TI  - Does the degree of intratumoural microvessel density and VEGF expression have
      prognostic significance in osteosarcoma?
AB  - The role of angiogenesis as a prognostic indicator in cancer has been extensively
      studied in recent times with several studies demonstrating a positive correlation
      for various malignant tumours. However, the role of angiogenesis in osteosarcoma
      remains a topic of debate. In this study, we aim to evaluate the significance of
      intratumoural microvessel density (MVD) and the degree of vascular epithelial
      growth factor (VEGF) expression as markers of angiogenesis and correlate this
      with disease outcome. Archival paraffin-embedded pre-treatment biopsy tissue of
      patients treated at St. Vincent's Hospital, Melbourne, with non-metastatic
      osteosarcoma at initial diagnosis was reviewed. Tissue was processed for
      immunofluorescent staining of the microvascular endothelial cells with antibodies
      directed against CD31 and CD34. The degree of angiogenesis was assessed, as
      determined by the microvessel density (MVD). Further histological examination was
      performed to assess the degree of VEGF expression. Histological observations were
      correlated with various clinicopathological factors and patient outcome in terms
      of recurrence, metastasis and death. Twenty-five cases were reviewed, 15 were
      male and 10 were female, and the median age was 26 years (range, 13-85). The mean
      follow-up was 21.5 months (range, 3-75 months). The median MVD was 43
      microvessels/0.26 mm2 (range, 25-54) and 46 microvessels/0.26 mm2 (range, 30-58)
      for CD31 and CD34, respectively. Despite the moderate to high vascularity, there
      was no significant difference noted between the MVD and disease outcome factors
      for both CD31 and CD34. There was a trend towards a higher MVD in patients aged >
      40 years compared to those < 40 years (p = 0.110 for CD31 and p = 0.097 for
      CD34). In terms of VEGF expression, 24 of 25 cases demonstrated either moderate
      or strong expression; however, no prognostic significance was determined. In this
      study, we were able to demonstrate that osteosarcoma is a relatively vascular
      tumour; however, the degree of MVD and VEGF expression does not provide
      prognostic information. It is likely that angiogenesis plays a key role in the
      pathogenesis of osteosarcoma and is, therefore, a potential target for novel anti
      angiogenic therapies.

PMID- 16786119
TI  - Effect of hepatocyte growth factor on endogenous hepatocarcinogenesis in rats fed
      a choline-deficient L-amino acid-defined diet.
AB  - Hepatocyte growth factor (HGF) is a promising agent for the treatment of
      intractable liver disease, due to its mitogenic, anti-apoptotic, and anti
      fibrotic effects. We investigated the effect of recombinant human HGF (rh-HGF) on
      the development of both hepatocellular carcinoma (HCC) and preneoplastic nodules
      in rats fed a choline-deficient L-amino acid-defined (CDAA) diet, an animal model
      of hepatocarcinogenesis resembling human development of HCC with cirrhosis. From
      weeks 13 to 48 of the CDAA diet, rh-HGF (0.1 or 0.5 mg/kg/day) was administered
      intravenously to rats in four-week cycles, with treatment for five consecutive
      days of each week for two weeks, followed by a two-week washout period. Treatment
      with rh-HGF significantly inhibited the development of preneoplastic nodules in a
      dose-dependent manner at 24 weeks. Although the numbers and areas of the
      preneoplastic nodules in rats treated with rh-HGF were equivalent to those in
      mock-treated rats by 60 weeks, the incidence of HCC was reduced by HGF treatment.
      Although one rat treated with low-dose rh-HGF exhibited a massive HCC, which
      occupied almost the whole liver, and lung metastases, HGF treatment did not
      increase the overall frequency of HCC. Administration of high-dose rh-HGF,
      however, induced an increase in the urinary excretion of albumin, leading to
      decreased serum albumin at 60 weeks. These results indicate that long-term
      administration of rh-HGF does not accelerate hepatocarcinogenesis in rats fed a
      CDAA diet. However, these findings do not completely exclude the potential of HGF
      induced hepatocarcinogenesis; this issue must be resolved before rh-HGF can be
      used for patients with intractable liver diseases, especially those with
      cirrhosis.

PMID- 16786120
TI  - Metronomic treatment of temozolomide inhibits tumor cell growth through reduction
      of angiogenesis and augmentation of apoptosis in orthotopic models of gliomas.
AB  - Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Temozolomide
      (TMZ), a methylating agent is one of the most effective chemotherapeutic agents
      against glioblastoma. To overcome the problem that most of these tumors become
      resistant to chemotherapeutic regimens within a year, we investigated the
      antitumor efficacy of metronomic administration of low-dose TMZ in in vitro cell
      proliferation/cytotoxicity assay and in vivo rat and nude mouse orthotopic glioma
      model. By in vitro assay, we elucidated that C6/LacZ rat glioma cells were more
      resistant to metronomic treatment of TMZ than U-87MG human glioblastoma cells and
      bEnd.3 mouse brain endothelial cells. Compared with the conventional
      chemotherapeutic regimen of TMZ, we found that frequent administration of TMZ at
      a low dose (metronomic treatment) markedly inhibited angiogenesis as well as
      tumor growth in a TMZ-resistant C6/LacZ rat glioma model. In addition, metronomic
      treatment of TMZ significantly augmented apoptosis of tumor cells in this model.
      For the TMZ-sensitive U-87MG cells, even with a very low dose of TMZ, which is
      not effective to reduce tumor mass, the metronomic treatment of TMZ reduced the
      microvessel density, i.e. angiogenesis, in a nude mouse orthotopic model. In
      conclusion, for both models, the metronomic treatment of TMZ decreased
      angiogenesis. Especially, in TMZ-resistant glioma cells, this regimen increased
      apoptosis of tumor cells and decreased tumor growth. The metronomic treatment of
      TMZ in orthotopic glioma models demonstrated a successful antiangiogenic effect
      which can overcome the chemoresistance in conventional TMZ chemotherapy.

PMID- 16786121
TI  - Loss of protein expression of hMLH1 and hMSH2 with double primary carcinomas of
      the stomach and colorectum.
AB  - The frequency of synchronous or metachronous multiple primary carcinomas in
      patients with gastrointestinal carcinoma or colorectal carcinoma (CRC) has been
      reported to be approximately 10%. We determined the role of hMSH2 and hMLH1 in
      double carcinomas with both GC and CRC. Fifty-six patients with synchronous or
      metachronous colorectal carcinoma with gastric carcinoma (CRC with GC), and 69
      patients with CRC alone was included in our study. We investigated their
      clinicopathological characteristics, family history and immunohistochemical
      stains of hMSH2 and hMLH1 were compared between the patients with CRC alone and
      those with both CRC with GC. The defective protein expression of hMSH1 and/or
      hMLH1 in colorectal carcinomas was significantly higher in patients with both CRC
      with GC than in those with CRC alone (p < 0.0001). The survival rate in patients
      with both CRC with GC was significantly lower than that in those with CRC alone
      (p < 0.01), in addition, the survival rate in patients with defective protein
      expression of hMSH2 and/or hMLH1 was higher than in those with a positive protein
      expression of hMSH2 and/or hMLH1 in CRC with GC (p < 0.05). The incidence of
      defective protein expression of hMSH2 and/or hMLH1 in CRC with GC patients
      suggests that abnormalities in the function of hMSH2 and hMLH1 may play an
      important role in carcinogenesis. Our findings indicate that the CRC patients who
      demonstrate a defective protein expression of hMSH2 and/or hMLH1 have a higher
      risk of developing secondary carcinoma in the gastrointestinal tract.

PMID- 16786122
TI  - The role of matrix metalloproteinases and tissue inhibitors of matrix
      metalloproteinase in microcystic meningiomas.
AB  - We studied the expression of matrix metalloproteinases (MMP) and tissue
      inhibitors of matrix metalloproteinase (TIMP) in microcystic meningiomas to
      investigate a possible underlying mechanism for the development of microcysts and
      of peritumoral edema, which are frequent characteristics of this rare subtype.
      Between October 1995 and June 2004, 10 of 19 patients who had histologically
      confirmed pure microcystic meningiomas were enrolled in the study. Six patients
      with meningothelial meningiomas, three with atypical meningiomas, and one with a
      transitional meningioma were included as a control group. Immunohistochemistry
      with paraffin blocks and real-time RT-PCR analysis for MMP-2, MMP-9, TIMP-1, TIMP
      2 and vascular endothelial growth factor (VEGF) were performed using stored
      frozen tissues. Compared with the control group, MMP-9 was invariably and highly
      expressed in immunohistochemical staining of microcystic meningiomas. MMP-2, TIMP
      1, TIMP-2 and VEGF were weakly expressed or not expressed in both microcystic and
      non-microcystic meningiomas. Real-time RT-PCR showed increased ratios of MMP-9 to
      TIMP-1 in microcystic meningiomas compared with the control group (55.855 +/-
      106.353 vs. 1.858 +/- 2.575, respectively; p = 0.00). The expression of MMP-2
      (0.72 +/- 1.20 vs. 2.54 +/- 3.01, p = 0.01) and TIMP-2 (1.22 +/- 1.67 vs. 1.61 +/
      1.82, p = 0.02) was higher in the control group. The results suggested that the
      increased ratio of MMP-9 to TIMP-1 might be associated with the formation of
      microcysts and peritumoral edema in microcystic meningioma.

PMID- 16786123
TI  - Predictive and prognostic role of activated mammalian target of rapamycin in
      cervical cancer treated with cisplatin-based neoadjuvant chemotherapy.
AB  - The present study was designed to clarify the expression and prognostic
      significance of activated Akt and mTOR in cervical cancer and their correlation
      with response to neoadjuvant chemotherapy (NAC). Immunohistochemical analysis for
      p-Akt and p-mTOR expression was performed on paraffin-embedded biopsy specimens
      from 25 patients with advanced cervical cancer (stage Ib2-IIb). We correlated
      this finding with various clinicopathological variables and prognosis by uni- and
      multivariate analyses. All patients received cisplatin-based NAC, and primary
      tumor response was evaluated by RECIST criteria and then classified as a positive
      or negative response. Activation of Akt was detected in the cytoplasm and nucleus
      of the cancer cells in 12 patients (48%), whereas p-mTOR was detected in the
      cytoplasm and membrane of the cancer cells in 13 patients (52%). Post NAC
      evaluation of the primary tumor revealed 68% (17/25) responsive tumors. The
      expression of p-mTOR and distant metastasis significantly correlated with the
      response to NAC (p = 0.0101 and p = 0.0107); however, there was no significant
      correlation between p-Akt and p-mTOR expression and any of the
      clinicopathological characteristics of the patients. In the univariate analysis,
      activated Akt and mTOR were found to be significant prognostic indicators (p <
      0.05). In multivariate analysis, p-mTOR expression retained its significance as
      an independent poor prognostic marker (p = 0.0178). In summary, our present study
      showed that cervical cancer expressed Akt and mTOR activation. Moreover, the
      expression of phosphorylated mTOR may have a role as a marker to predict response
      to chemotherapy and survival of cervical cancer patients who are treated with
      cisplatin-based neoadjuvant chemotherapy. Our results suggest that the mTOR
      cascade may be a promising target for therapeutic intervention in cervical
      cancer.

PMID- 16786124
TI  - The TP53 codon 72 polymorphism and predisposition to adrenocortical cancer in
      Polish patients.
AB  - The TP53 polymorphism occurs at codon 72 of exon 4 with two alleles encoding
      either arginine or proline. The association between this common polymorphism and
      risk of different cancers has been extensive studied, however various reports are
      controversial. We have analyzed the 72Pro polymorphic variant in patients with
      adrenocortical tumors to evaluate whether 72G--> C substitution at codon 72 of
      TP53 gene may be associated with increased risk for malignancy in adrenal cortex
      in comparison to the control group. DNA extracted from peripheral leucocytes of
      46 Polish patients with adrenocortical tumors (17 malignant and 29 benign) and 50
      controls was examined by PCR-HD method followed by direct sequencing. TP53
      polymorphism in codon 72 was found in 47% of ACC cases, in 28% of patients with
      adenomas and in 24% of controls. The genotype Arg/Arg, Arg/Pro and Pro/Pro
      distribution was respectively 53%/35%/12% for cancers, 72%/28%/0% for benign
      tumors and 76%/24%/0% for controls. High frequency of 72Pro allele in patients
      with carcinoma (29%) in comparison to the benign tumors (14%) and controls (12%)
      was statistically analyzed. We found that 72Pro variant of TP53 gene was
      associated with a significantly increased risk of ACC (OR = 3.05; 95% CI = 1.17
      7.91, p=0.03). Our results suggest that the TP53 codon 72 polymorphism could be
      associated with susceptibility for adrenocortical cancer in the examined Polish
      patients.

PMID- 16786125
TI  - Development of a self-proliferating Leydig cell line: a hyper-sensitive E
      screening model.
AB  - The mechanisms of estrogenic endocrine disruption on the male reproductive tract
      are poorly understood. In order to examine estrogenic properties of xenobiotic
      chemicals on male tissues, we have developed a mouse Leydig cell line (TM3-SF)
      that self-proliferates under serum-free conditions. This cell line was derived
      from ATCC's cell line, TM3. The development of TM3-SF was accomplished over a 4
      month period by a progressive serum starvation of the original TM3 cells. The
      newly established cell line was maintained under serum-free conditions for 20
      passages prior to testing. Sensitivity of the TM3-SF cells to estrogens was
      assayed by cell proliferation studies. A total of four compounds,
      diethylstilbestrol (DES), 17beta-estradiol, 17alpha-estradiol, and Bis-phenol A,
      were tested. Significant increases in cell proliferation occurred at various
      concentrations ranging from 1 pg/ml to 100 ng/ml for all four compounds. The
      order of potency observed was DES > Bis-phenol A > 17beta-estradiol and > 17alpha
      estradiol. In addition, we investigated the mechanism for the self-proliferative
      properties of TM3-SF. The results of these trials indicate that either inhibin or
      activin is a primary growth factor for this cell line as a 50% inhibition of
      growth was noted when cell cultures were exposed to the anti-betaa subunit of
      inhibin/activin. Furthermore, the addition of the anti-betaa subunit of
      inhibin/activin blocked the DES-induced proliferation of TM3-SF. We conclude that
      the growth of TM3-SF cells is estrogen sensitive and that either inhibin or
      activin is involved in the self-regulation of growth.

PMID- 16786126
TI  - Activation of the PKB/Akt pathway in histological benign prostatic tissue
      adjacent to the primary malignant lesions.
AB  - In order to evaluate the molecular heterogeneity of prostate cancer, this study
      examined the expression of Akt-pathway related parameters within the cancerous
      prostate gland. PTEN, p-Akt and p27kip1 are known to be altered in prostate
      cancer. Tissue samples from malignant, tumor adjacent benign and benign areas of
      25 whole mounted prostate cancer specimens were processed to 583 tissue
      microarray cores. Immunohistochemically determined biomarker expression was
      correlated to the different localizations. p-Akt and p27kip1 showed increased
      staining in malignant tissue compared to the respective benign tissue (p < 0.01
      and p < 0.05). The adjacent but histologically benign tissue had increased levels
      (p < 0.05 and p < 0.01), whereas no significant difference was found between the
      adjacent and malignant regions. A highly significant correlation of p-Akt and
      p27kip1 in benign tissue (p < 0.001) was lost in the adjacent areas and in the
      malignant tissue (p = 0.054 and p = 0.12). In tendency, PTEN expression was
      decreased in the malignant regions and revealed the highest staining in the
      adjacent zone. According to the results obtained, the expression of p-Akt and
      p27kip1 was increased in both the adjacent microscopically benign tissue as well
      as the primary tumors when compared with the histologically benign tissue
      specimens that served as biological control. The increased expression of PTEN
      indicates its regulatory function in the initial steps of a deteriorated cell
      cycle control as well as uncontrolled cellular proliferation, for example, which
      seem to be present in the normal prostatic tissue surrounding the primary
      malignant lesion. The addition of molecular markers to a 'classical'
      histopathological approach might contribute to an enhanced sensitivity of
      analytical approaches aimed at the detection of malignant or premalignant lesions
      within prostatic biopsies.

PMID- 16786127
TI  - Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and
      established cell lines.
AB  - Alterations of the Smad4 gene, identified as a mediator of the transforming
      growth factor-beta pathway, were investigated in hamster pancreatic duct
      adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters
      received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated
      exposure to an augmentation pressure regimen consisting of a choline-deficient
      diet combined with DL-ethionine then L-methionine and a further administration of
      20 mg/kg BOP. A total of 12 PDAs obtained 10 weeks after beginning the experiment
      and three cell lines established from subcutaneously transplantable PDAs in
      syngeneic hamsters were examined for mutations using reverse transcription
      polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP)
      analysis. A mutation was detected in only one PDA (1/12, 8.3%) in the form of an
      ACC to ATC (Thr to IIe) transition at codon 73; none were detected in the three
      cell lines. No reduced or increased expression of the Smad4 gene was detected in
      any case using real-time quantitative RT-PCR. These results suggest that the
      Smad4 gene might play a role in limited fraction of BOP-induced pancreatic duct
      carcinogenesis in hamsters.

PMID- 16786128
TI  - Enhancement of GLI1-transcriptional activity by beta-catenin in human cancer
      cells.
AB  - The Hedgehog (Hh) signaling pathway and the Wnt signaling pathway are known to
      play important roles in carcinogenesis and the progression of various human
      malignant tumors. Although a relationship between these two pathways has recently
      been reported, the mechanism by which beta-catenin, one of the key molecules of
      the Wnt signaling pathway, influences the Hh pathway has not yet been revealed in
      detail. To clarify the role of beta-catenin in relation to the Hh signaling
      pathway, we transfected GLI1 and beta-catenin expression constructs into human
      malignant cells, including stomach, colon, and lung cancers, and evaluated the
      luciferase activity of GLI-responsive reporter constructs. While exogenous GLI1
      increased the luciferase activity, exogenous beta-catenin also enhanced the
      activity under overexpression of GLI1. However, co-transfection with T-cell
      factor (TCF)-4 or lymphocyte enhancer factor (LEF)-1 did not influence the
      activity, indicating that the enhancement of beta-catenin in relation to the Hh
      signaling pathway is not TCF/LEF-dependent. Our results suggest that beta-catenin
      might be involved in the Hh signaling pathway via enhancement of the
      transcriptional activity of GLI.

PMID- 16786129
TI  - Acquired resistance to imatinib and secondary KIT exon 13 mutation in
      gastrointestinal stromal tumour.
AB  - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours
      of the gastrointestinal tract. Most of them have an activating mutation of KIT or
      PDGFRalpha tyrosine-kinase receptors. Imatinib is a selective tyrosine-kinase
      inhibitor of ABL, KIT and PDGFR, and provides a clinical benefit in about 85% of
      patients with advanced GIST. Unfortunately, secondary resistance following
      initial responses occurs in most of the cases, and molecular mechanisms are
      poorly understood. We sequenced KIT and PGDFRalpha exons from one patient with
      GIST before and after the development of imatinib resistance. We identified, in
      addition to a primary mutation in exon 9, a secondary mutation in KIT exon 13
      (first kinase domain) in the resistant sample. We demonstrate for the first time
      the feasibility of sequencing such samples removed by non-surgical biopsies
      during imatinib therapy. Such a approach, far less invasive than surgery and
      combined with sequencing, will likely help in better tailoring the treatment of
      advanced GISTs and understanding the mechanisms of resistance and response to
      imatinib.

PMID- 16786130
TI  - Immunohistochemical study of chymase-positive mast cells in inflammatory bowel
      disease.
AB  - Mast cell-derived chymase promotes inflammatory responses and tissue fibrosis.
      Although previous studies have reported changes in the number of mucosal mast
      cells in inflammatory bowel disease (IBD), the behaviour of chymase
      immunopositive mast cells has not been studied. In this study, we
      immunohistochemically investigated chymase immunopositive mast cells in the
      inflamed mucosa of IBD patients. Surgically-obtained or biopsy specimens from 10
      patients with ulcerative colitis (UC), 10 patients with Crohn's disease (CD) and
      10 normal colorectal tissue specimens were used. The chymase immunopositive cells
      were identified by immunohistochemical analysis using a monoclonal anti-human
      chymase antibody. In the normal colonic mucosa, a small number of chymase
      immunopositive mast cells were detected at the basal sites of the mucosa. There
      were no immunopositive cells in the submucosa. Chymase immunopositive mast cells
      were similarly observed in the inactive UC mucosa, but these cells decreased
      significantly in number in the active UC mucosa. In the inactive CD mucosa, the
      number of chymase immunopositive mast cells increased significantly (P < 0.05),
      and this was more clearly observed in the active CD mucosa. Furthermore, in the
      active CD mucosa, these cells were detected in the submucosa, propria muscularis,
      and surrounding fatty tissue. These observations suggest a crucial role for
      chymase immunopositive mast cells in the pathophysiology of CD. Since intestinal
      fibrotic changes such as stricture formation are a characteristic feature of CD,
      chymase immunopositive mast cells may act as a stimulus for the process of tissue
      fibrosis and tissue remodelling in the pathophysiology of CD.

PMID- 16786131
TI  - Chemokine receptor CCR7 enhances intrahepatic and lymphatic dissemination of
      human hepatocellular cancer.
AB  - Despite many pathophysiological analyses, the process of tumor dissemination of
      hepatocellular carcinoma (HCC) remains vague. In diverse tumor entities,
      expression of the chemokine receptor, CCR7, has been linked to tumor
      dissemination and poor prognosis. Therefore, we evaluated, whether CCR7 exerts
      similar effects in human HCC. CCR7 expression analysis was performed in vitro on
      human hepatoma cell lines (Huh7, Hep3B, wt HepG2, p53 dominant negative
      transfected HepG2). In addition, CCR7 expression was evaluated in 39 patients
      with hepatocellular cancer and correlated with both, tumor and patients
      characteristics. Human hepatocellular carcinoma samples and hepatoma cell lines
      displayed variable intensities of CCR7 expression. In patients, CCR7 expression
      was significantly associated with progressed local tumors (P = 0.02) and
      lymphatic metastasis (P = 0.02). Strong expression of CCR7 promotes intrahepatic
      and lymphatic HCC dissemination.

PMID- 16786132
TI  - Extraskeletal myxoid chondrosarcoma arising from the clavicle.
AB  - This report presents an extremely rare case of extraskeletal myxoid
      chondrosarcoma (EMC) arising from the clavicular periosteum. To the best of our
      knowledge, this may be the first detailed report of its clinicopathological
      findings. The patient was a 48-year-old man. Plain radiography and CT did not
      demonstrate any osteolytic lesion or periosteal reaction in the right clavicle.
      However, MRI showed an isosignal-intensity mass on T1-weighted images and a
      homogeneous high signal intensity lesion on T2-weighted images. The histological
      findings of the widely resected tumor were consistent with the diagnosis of
      extraskeletal myxoid chondrosarcoma. Preoperative diagnosis of extraskeletal
      myxoid chondrosarcoma at an unusual location, as in this case, is difficult not
      only with imaging examinations alone, but sometimes even after histological
      examination of biopsy specimens.

PMID- 16786133
TI  - Erlotinib prevents pulmonary metastasis in curatively resected breast carcinoma
      using a mouse model.
AB  - Metastatic breast cancer is still defined as an incurable disease, with the lungs
      being the most common metastatic sites in breast cancer patients. Epidermal
      growth factor receptor (EGFR), a member of receptor tyrosine kinase family, is
      known to be involved in survival, migration, angiogenesis and metastasis of
      cancer. The spontaneous pulmonary metastasis mouse model was applied to evaluate
      the effects of the EGFR tyrosine kinase inhibitor, erlotinib, on the prevention
      of pulmonary metastasis in curatively resected breast carcinoma. The expression
      of EGF and EGFR was significantly strong in pulmonary metastatic nodules compared
      to those in primary breast carcinoma tissue. A treatment of erlotinib (oral
      gavage, 50 mg/kg/day, every day for 6 weeks) given to mastectomized mice
      inhibited the incidence of pulmonary metastasis. The number of metastatic
      pulmonary nodules was significantly reduced in the erlotinib-treated group
      compared with the control. Therefore, erlotinib may play a role in preventing
      pulmonary metastasis, which shows the strong expression of EGF and EGFR after
      curative resection of primary breast cancer.

PMID- 16786134
TI  - Childhood thyroid carcinoma with BRAFT1799A mutation shows unique pathological
      features of poor differentiation.
AB  - The prevalence of BRAFT1799A mutation in papillary thyroid carcinomas (PTCs)
      displays a marked age association: relatively high in adults and exceedingly low
      in childhood. We report a case of a 12-year-old Japanese female with PTC, the
      only one case that harbored BRAFT1799A mutation in a series of 46 childhood
      thyroid cancer tissues. On histology, the findings were so atypical that
      pathologists had repeatedly examined tumor sections to agree on the diagnosis of
      poorly differentiated follicular carcinoma. Upon molecular investigation,
      BRAFT1799A was detected in DNA extracted from paraffin-embedded material, whereas
      TP53 was wild-type. Since BRAFT1799A is strictly limited to PTCs,
      immunohistochemical staining for CD15, a specific marker for papillary carcinoma,
      was performed to verify the diagnosis. A small tumor area with papillary-like
      structure was stained positive. These findings strongly suggest that this case is
      a poorly differentiated carcinoma that arose from PTC and implies a possible
      association of BRAF mutation with dedifferentiated phenotype of PTCs.

PMID- 16786135
TI  - Role of p16 and p14ARF in radio- and chemosensitivity of malignant gliomas.
AB  - In addition to cytoreductive surgery, most patients with malignant gliomas also
      undergo radio- and chemotherapy. An improved understanding of the molecular
      genetic mechanisms underlying the radio- and chemosensitivity of gliomas may help
      to identify glioma patients who will benefit from aggressive and, therefore,
      potentially toxic adjuvant treatment. It may also allow for the development of
      new therapies aimed at improving the response of these tumors towards chemo- and
      radiotherapy. The INK4a gene products, p16 and p14ARF, have been suggested as
      potential regulators of glioma chemo- and radiosensitivity. We have used
      tetracycline controlled expression of p16 and plasmid-based p14ARF expression to
      study the chemo- and radiosensitivity of glioma cell lines. Ectopic p16
      sensitized U-87MG cells towards treatment with vincristine and possibly also BCNU
      by approximately 1.5 to 2-fold, and towards ionizing radiation by a factor of
      1.5. p14ARF expression was found to render U-87MG cells 2-fold more
      radioresistant than controls. These findings support a role for p16 and p14ARF as
      modulators of the radio-and chemosensitivity of gliomas. Further studies of the
      role of cell cycle regulators in glioma chemo- and radio-sensitivity seem
      warranted. We would like to point out that such candidate genes which may code
      for potent growth suppressors (like p16) or even toxic gene products can be
      successfully investigated using the approach detailed in this manuscript.

PMID- 16786136
TI  - A novel metronomic chemotherapy regimen of weekly platinum and daily oral
      etoposide in high-risk non-small cell lung cancer patients.
AB  - The aim of this pilot phase II trial was to investigate the toxicity and anti
      tumour activity of a novel metronomic regimen of weekly cisplatin (CDDP) and oral
      etoposide (VP16) in high-risk patients with advanced NSCLC. The study enrolled 31
      high-risk patients (27 men and 4 women aged 16-82 years; mean, 64.3) with NSCLC
      (18 stage IIIB and 13 stage IV) and an ECOG performance status of < or = 3, all
      of whom received weekly CDDP 30 mg/m2 iv on days 1, 8, 14 and 28 of each cycle
      and oral daily etoposide 50 mg/m2 on 21 of the 28 days. The most frequent adverse
      events were grade III leukopenia and anemia; nevertheless, three patients died of
      pulmonary embolism after 2, 3 and 6 weeks of treatment. The objective response
      (OR) rate was 45.2% (2 complete and 12 partial), and the disease control rate was
      58.1% (14 ORs and 4 disease stabilisations). The mean time to progression and
      survival were respectively nine months (95% CI, 6.3-15.8 months) and thirteen
      months (95% CI, 9.1-20.5 months). Pharmacological analysis showed that this
      metronomic regimen allows a much greater median monthly area under the curve of
      CDDP and VP16 than conventional treatment schedules. Our findings also suggest
      that this treatment schedule may affect tumour growth and neoangiogenesis by
      changing peripheral blood vascular-endothelial growth factor levels. These
      preliminary results indicate that our metronomic regimen is well tolerated and
      active, even in patients with a very poor prognosis.

PMID- 16786137
TI  - Different mechanisms for anti-tumor effects of low- and high-dose
      cyclophosphamide.
AB  - It is known that, besides its direct cytotoxic effect as an alkylating
      chemotherapeutic agent, cyclophosphamide also has immuno-modulatory effects, such
      as depletion of CD4+CD25+ regulatory T cells. However, its optimal concentration
      has not yet been fully elucidated. Therefore, we first compared the effects of
      different doses of cyclophosphamide on T cell subsets including CD4+CD25+ T cells
      in mice. Cyclophosphamide (20 mg/kg) decreased the numbers of splenocytes, CD4+
      and CD8+ T cells by approximately 50%, while a decline in CD4+CD25+ T cell number
      was more profound, leading to the remarkably lower ratios of CD4+CD25+ T cells to
      CD4+ T cells. In contrast, 200 mg/kg cyclophosphamide severely decreased the
      numbers of all the T cell subsets by > 90% although the decreased ratios of
      CD4+CD25+ T cells to CD4+ T cells were still observed. Next, low-dose
      cyclophosphamide significantly inhibited in vivo growth of murine hepatoma MH129
      tumor in immuno-competent but not immuno-deficient mice. This anti-tumor effect
      was abolished by CD4+CD25+ T cell repletion. In contrast, high-dose
      cyclophosphamide exhibited similar anti-tumor effects in both mice. In addition,
      contrary to antibody-mediated CD4+CD25+ T cell depletion, administration of low
      dose cyclophosphamide after tumor inoculation was more efficacious than the prior
      administration. Our data show that low-dose cyclophosphamide selectively depletes
      CD4+CD25+ T cells, leading to enhanced anti-tumor effects against pre-existing
      tumors, while the anti-tumor effect of high-dose cyclophosphamide is solely
      attributed to its direct cytotoxicity. These findings appear to be highly crucial
      in a clinical setting of combined chemotherapy and immunotherapy for cancer
      treatment.

PMID- 16786138
TI  - A new strategy using autologous dendritic cells and lymphokine-activated killer
      cells for cancer immunotherapy: efficient maturation of DCs by co-culture with
      LAK cells in vitro.
AB  - Among a variety of antigen presenting cells (APCs), accumulating results support
      that the mature dendritic cell (DC) has the potential to induce efficient
      cytotoxic T lymphocyte (CTL) responses in the context of peptide-based
      immunotherapy. DCs have been known to assume the mature form by signaling through
      the CD40-CD40 ligand (CD40L) interaction, which may be provided by activated CD4+
      T cells expressing abundant CD40L molecules on their surfaces. Here, we report
      that DCs generated from peripheral blood monocytes obtained from patients with
      advanced cancer exhibit a mature phenotype after co-culturing with autologous
      lymphokine-activated killer (LAK) cells generated by the stimulation of
      peripheral blood mononuclear cells with anti-CD3 monoclonal antibody (mAb) and
      interleukin (IL)-2. Part of this process appeared to be dependent on the
      expression of CD40L on the surface of LAK cells, although it was also suggested
      that some other humoral factors produced by LAK cells may be involved in this
      effect as well. DCs derived from the donors, of which LAK cells demonstrated a
      higher Th1/Th2 ratio upon activation determined by the intracellular detection of
      interferon-gamma and IL-4, showed more efficient maturation upon co-culture with
      LAK cells than DCs from donors with a low Th1/Th2 ratio. Importantly, these
      matured DCs induced a two-times stronger antigen-presenting capacity measured by
      an allo-reactive mixed lymphocytes reaction assay as compared to immature DCs.
      These results imply the use of the combination of DCs and LAK cells for
      immunotherapy against cancer.

PMID- 16786140
TI  - Cellular processing in the SW1222 cell line of mAb A33 directly and indirectly
      radiohalogenated.
AB  - Investigations into the cellular processing of radiolabeled monoclonal antibodies
      (mAbs) for their further use in radioimmunodiagnosis and cancer therapy are
      needed in order to understand the fate of internalized and catabolized mAbs. The
      anti-colorectal cancer mAb, A33, was labelled with 76Br and 125I using the direct
      Chloramine-T method, or by labelling N-succinimidyl para-(tri-methylstannyl)
      benzoate and its further conjugation to the mAb. The cellular processing of the
      four conjugates was investigated in SW1222 cells in vitro. Uptake of mAb was
      rapid, peaking after 14-16 h. Intracellular degradation was slow and the early
      loss of radioactivity was due to dissociation of cell-surface bound mAb. The
      indirect labelling resulted in stronger binding of the mAb as well as prolonged
      intracellular retention of the radiolabel. Direct and indirect halogen
      radiolabelling results in different cell-processing patterns of radiolabels, and
      radioactive catabolic products follow different routes of cellular excretion. The
      results of this cellular study indicate that indirect labelling is preferable to
      the direct Chloramine-T method.

PMID- 16786139
TI  - PEA3 cooperates with c-Jun in regulation of HER2/neu transcription.
AB  - HER2/neu overexpressing breast tumors exhibit an increase in polyomavirus
      enhancer activator 3 (PEA3) expression. We examined the relationship between
      HER2/neu transcriptional activation and PEA3 in cooperation with c-Jun. HER2/neu
      promoter activity was decreased by deleting PEA3 binding site, and was
      downregulated when the PEA3 binding site was mutated. PEA3 and c-Jun each weakly
      enhanced luciferase expression of the HER2/neu promoter. However, the HER2/neu
      promoter response to PEA3 was considerably enhanced by c-Jun. Thus, we examined
      the interaction of PEA3 with c-Jun by the two-hybrid system, the transcriptional
      activity of PEA3 was specifically enhanced by c-Jun. When PEA3, c-Jun and
      coactivator p300 were cotransfected in MCF7 cells, the transcriptional activity
      of HER2/neu was increased by up to 20-fold. PEA3 and c-Jun-induced transcription
      of HER2/neu promoter was repressed by cotransfection of the dominant negative of
      p300. These results suggest that PEA3 and c-Jun stimulated synergistically the
      HER2/neu gene transcription with p300.

PMID- 16786141
TI  - Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class I
      matched allogeneic tumor cells.
AB  - A 29-year-old female breast cancer patient with multiple bone metastases (HLA-A2)
      was treated with adoptive transfer using autologous peripheral blood mononuclear
      cells (PBMCs) activated with the HLA-A2-matched allogeneic GC022588 gastric
      cancer cell line and interleukin-2 plus an immobilized anti-CD3 antibody culture
      system. The relief of bone pain in parallel with a decrease of serum
      carcinoembryonic antigen levels was obtained just after the administration of
      GC022588-activated effector lymphocytes, and a good quality of life was
      accomplished for 4 months. The GC022588-activated effector lymphocytes included
      44% CD4+, 77% CD8+, and 26% CD4+CD8+ phenotypes, and expressed 25% killing
      activity against GC022588 stimulator cells at an E/T ratio of 50:1. T cell
      receptor (TCR) usage analysis for the effector cells showed oligoclonal
      expression of TCRVbeta1, 3, 9, and 11, especially TCRVbeta5.2, 12, 13.1 and 17,
      and their killing activity was significantly inhibited in the presence of anti
      TCRalphabeta antibody and anti-TCRVbeta12 antibody. SSCP analysis revealed
      clonotypic bands of TCRVbeta12. These results suggest that shared antigens exist
      between breast and gastric adenocarcinomas. Allogeneic tumor cells can stimulate
      PBMCs to generate effector cells with selected TCRCDR3 usages that recognize
      tumor antigens. These effector lymphocytes may be good candidates for the
      adoptive immunotherapy of cancer.

PMID- 16786142
TI  - Suppression of U937 human monocytic leukemia cell growth by dideoxypetrosynol A,
      a polyacetylene from the sponge Petrosia sp., via induction of Cdk inhibitor p16
      and down-regulation of pRB phosphorylation.
AB  - Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is
      known to exhibit significant selective cytotoxic activity against a small panel
      of human tumor cell lines, the mechanisms of which however, are poorly
      understood. The aim of the present study was to further elucidate the possible
      mechanisms by which dideoxypetrosynol A exerts its anti-proliferative action in
      cultured human monocytic leukemia U937 cells. We observed that the proliferation
      inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest in
      the cell cycle, the effects of which were associated with up-regulation of cyclin
      D1 and down-regulation of cyclin E, in a concentration-dependent manner without
      any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A
      markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore,
      down-regulation of phosphorylation of retinoblastoma protein (pRB) by this
      compound was associated with enhanced binding of pRB and transcription factor E2F
      1. Overall, our results demonstrate a combined mechanism involving the inhibition
      of pRB phosphorylation and induction of p16 as targets for dideoxypetrosynol A,
      may explain some of its anti-cancer effects.

PMID- 16786143
TI  - The relationship between survival and the expression of dihydropyrimidine
      dehydrogenase in patients with colorectal cancer.
AB  - Dihydropyrimidine dehydrogenase (DPD) is considered to be a key enzyme affecting
      the prognosis for patients with colorectal cancer. We investigated whether a
      correlation exists between the expression of DPD and survival in patients with
      colorectal cancer. The present study was designed to quantify the DPD level using
      an enzyme-linked immunosorbent assay in tumors and normal tissue specimens
      obtained from 22 colorectal cancer patients. There were no significant
      differences in the preoperative features, neither in the intra- and post
      operative findings of patients between the high DPD and low DPD groups in tumor
      tissue. In patients showing an expression of DPD in tumor tissue, the overall
      survival in the low DPD group tended to be longer than that in the high DPD group
      (P = 0.076). In contrast, in patients showing an expression of DPD in normal
      tissue, no significant difference was observed in the overall survival between
      the high DPD and low DPD groups (P = 0.358). In patients showing an expression of
      DPD in tumor tissue, the disease-free survival in the low DPD group was longer
      than that in the high DPD group (P = 0.046), whereas in patients showing an
      expression of DPD in normal tissue, no significant difference was seen in the
      disease-free survival between the high DPD and low DPD groups (P = 0.473). There
      tended to be a correlation between the DPD expression in tumor tissue and that in
      adjacent normal tissue (R = 0.390, P = 0.073). Based on these findings, we
      demonstrated the importance of DPD expression in tumor tissue as a prognostic
      factor in patients with colorectal cancer.

PMID- 16786144
TI  - Detection and expression of human papillomavirus oncogenes in non-small cell lung
      cancer.
AB  - Human papillomavirus (HPV) has been found in lung cancer cases with variable
      frequency. In the present study, we analysed a series of 38 patients with non
      small cell lung cancer (NSCLC) (21 paraffin-embedded archival samples and 17
      fresh surgical specimens) for the presence of E6 and E7 oncogenes of HPV16, 18
      and 31. Eight of the tumours were positive (21%): six HPV16, one HPV16+18, and
      one HPV31. The normal tissue surrounding the HPV-positive tumour was negative for
      the presence of the virus. Sequencing analysis of URR, of HPV16, which was the
      most frequently found HPV type in our cases, showed an adenosine deletion at
      nucleotide 7861 (E2-binding site) in four out of six patients. Sequencing of the
      entire E6 and E7 genes of HPV16 showed a T to G transition at nucleotide position
      350 of E6, in all examined cases. This mutation is associated to the European
      variant of HPV16. Analysis of E6 and E7 transcripts was performed on the six
      fresh surgical specimens infected by HPV16. Our study showed that all of the
      tumours investigated, except one, contained E6 and E7 transcripts. Only in one
      case could we identify an unspliced form of the E6 transcript. Our results
      strengthen the relationship between HPV and NSCLC and support the hypothesis that
      HPV infection could play a role in bronchial carcinogenesis.

PMID- 16786145
TI  - A single-center report on clinical features and treatment response in patients
      with intestinal T cell non-Hodgkin's lymphomas.
AB  - Intestinal T cell lymphomas are rare, but highly aggressive in their clinical
      course. Generally diagnosed in advanced stages and presenting as surgical
      emergencies, they also respond poorly to standard anti-lymphoma therapies. Since
      these lymphomas are still not well characterized, we aimed our retrospective
      research at the evaluation of clinical features and treatment response in
      patients with intestinal T cell lymphomas diagnosed between February 1996 and
      November 2004. Fifteen patients were identified from the Department of Pathology
      database at the Institute of Oncology Ljubljana. Details of history, physical
      examination, staging investigation, treatment and outcome were taken from patient
      records. Ten (67%) patients had enteropathy-associated T cell lymphoma (EATL) and
      5 (33%) had peripheral T cell lymphoma (PTCL). Surgery was performed on 11
      patients with 8 cases on an emergency basis; all visible disease was resected in
      only 3 patients. In the continuation of treatment, all 15 patients received
      chemotherapy (predominantly CHOP). Six patients were treated with field
      radiotherapy as a part of the first treatment. In total, complete response was
      achieved in 6 patients (40%) with a median duration of 5.3 months (range, 2 to 12
      months), stable disease in 3 patients (20%), and progressive disease in 6
      patients (40%). Results were better in patients with limited disease. The most
      frequent treatment complications were small bowel perforation, obstruction,
      gastrointestinal bleeding, and infection. Even though some patients underwent
      second- and third-line treatment, 13 (87%) of the total 15 patients died from
      progressive disease or complications of treatment. The actuarial 1- and 5-year
      survival rates were 33% and 9%, respectively. The prognosis and standard
      treatment of patients with intestinal T cell lymphomas are unsatisfactory with
      only a few long-term survivors. Therefore, earlier diagnosis and the development
      of more effective treatments are urgently required to improve the prospects of
      these patients.

PMID- 16786146
TI  - Malignant tumors in two ancient populations: An approach to historical tumor
      epidemiology.
AB  - The actual increase in the rate of malignant tumors has been ascribed to a higher
      life expectancy and the influence of various environmental factors. Herein, we
      present data on the frequency of malignant tumors in paleopathologically well
      defined historic populations. Thereby, we looked for malignant growth affecting
      the skeleton in three study populations of 905 individuals that have been
      excavated from the necropoles of Thebes-West and Abydos, Upper Egypt covering the
      time period between 3200 and 500 BC and 2547 individuals that have been buried in
      a Southern German ossuary dating from between AD 1400 and 1800. The tissue
      preservation of both the Egyptian and Southern German material was excellent. All
      available specimens were subjected to a very careful macroscopic examination;
      isolated findings were also radiologically investigated. In parallel,
      anthropological data, such as gender and age at death, were recorded. We
      identified 5 cases of malignant tumors affecting the skeleton in the Egyptian
      material and 13 cases affecting the skeletal material from Southern Germany. In
      most instances, multiple osteolytic lesions with slight osteoblastic reaction are
      strongly suggestive for metastatic carcinoma. Few cases with poorly reactive
      osteolyses were most compatible with plasmacytoma. Relative tumor frequencies on
      an age- and sex-adjusted population basis (using a mathematic model of skeletal
      involvement of malignant tumors in a well-defined English study population from
      AD 1901 to 1905) indicated that the tumor rates were not statistically different
      between ancient Egyptian, the historical Southern German and the recent English
      reference population. These observations indicate that malignant tumors were
      present in spatially and temporarily different populations over the last 4000
      years with an age- and gender-adjusted frequency not different from Western
      industrial populations of c. 100 years ago. Therefore, we conclude that the
      current rise in tumor frequencies in present populations is much more related to
      the higher life expectancy than primary environmental or genetic factors.

PMID- 16786147
TI  - DNA analysis as a tool for breast cancer malpractice determination: an
      interdisciplinary approach.
AB  - Malpractice in breast cancer can be seen as false-negative or false-positive
      findings which may result in either late or incorrect therapies. Biopsy material
      can be unintentionally interchanged, leading to incorrect treatment, and
      psychological damage to the patient. There is an obvious need for
      individualization of the tissue samples in such cases. In this study we used a
      multidisciplinary approach to integrate DNA technology that has been standardized
      and used in forensic science for other purposes, mainly to prove malpractice that
      has been the result of interchanging tissue samples in breast cancer. The main
      focus of the study was to evaluate the applicability of the technique, therefore
      we studied the samples of a 58-year-old female for whom the result of
      pathological analysis was reported as 'invasive ductal carcinoma'. The patient
      was surgically treated by a modified mastectomy technique and referred for
      chemotherapy. Prior to chemotherapy we found that the tissue samples analyzed did
      not belong to the patient in question. We used a battery of 15 polymorphic STR
      loci to identify the sample and we had strong evidence for exclusion of the
      patient. The analysis was done on both blood and buccal swab of the patient and
      on the tissue sample. We concluded that the technique is applicable and useful;
      however care should be taken in the interpretation of the results because the
      mutations in the tumoral tissues are very well known. Therefore, the maximum of
      informative loci should be studied and loss of heterozygosity should always be
      considered. We should also have in mind the possibility of intentional
      interchange which gives the results value in medico-legal investigations.

PMID- 16786148
TI  - Expression of breast cancer specific gene-1 (BCSG-1/gamma-synuclein) is
      associated with tumour grade but not with clinical outcome of patients with
      breast cancer.
AB  - This study examined the expression and distribution of BCSG-1 in human breast
      cancer tissue. IHC revealed that BCSG-1 was primarily seen as a cytosolic
      protein, weakly staining normal mammary epithelial cells but increased in breast
      tumour cells. Q-PCR revealed that node negative and positive tumours had similar
      levels of BCSG-1 transcript and BCSG-1/CK19 ratio. There were significantly
      higher levels in grade 2 and grade 3 tumours compared to grade 1. Patients with
      NPI (Nottingham prognostic indicator) < 3.4, had a predicted 80% 15-year
      survival. After a 10-year follow-up, no significant difference was seen between
      tumours from patients remaining disease-free and those who died of breast cancer.
      The levels of BCSG-1 significantly correlated with an associated molecule,
      transglutaminase-3 (r = 0.307, P < 0.05), and weakly with transglutaminase-7 (r =
      0.183). BCSG-1 is increased in breast tumour cells, is negatively associated with
      tumour grade and significantly correlates with levels of transglutaminase-3.

PMID- 16786149
TI  - HIV-1 infection: is it time to reconsider our concepts?
AB  - The long asymptomatic phase of HIV infection is critical in the progression to
      AIDS. It probably reflects an ancestral relationship with lentiviruses stemming
      from the primate-simian immunodeficiency virus evolutionary pathway leading to an
      idiosyncratic immune tolerance, which needs to be understood if effective
      vaccines are to be rationally designed. The majority of CD4+ T cells that die due
      to HIV-1 in the asymptomatic phase are not infected with the virus. Transmission
      of the predominant HIV-1 R5 variants to T cells is mediated by infected monocyte
      derived macrophages. The two cell populations come into intimate contact mainly
      in the lymph nodes during antigen presentation where there is also active viral
      replication. We propose that HIV exploits antigen presentation to access target T
      cells and evade immune surveillance. This is achieved at the assembly point of an
      immunological synapse between an antigen presenting, HIV-1-infected macrophage
      and a responding effector/memory CD4+ T cell. Viral envelope gp120 glycoproteins
      proximal to MHC II molecules cross-link with T cell CD4 molecules, thus
      establishing a supra molecular immuno-viral synapse. The interaction results in
      conformational changes of gp120 exposing its V3 domain. Ionic interaction of this
      domain with the synapse-recruited chemokine receptor CCR5 dimerizes the receptor
      triggering intracellular signals that contribute to T cell receptor
      transactivation pathways and subsequent enhancement of T cell activation. HIV
      downregulated MHC II gives weak immune complexes. Disruption of the immuno-viral
      synapse before completion of cell entry is a frequent outcome condemning the
      responding T cell to a premature activation-induced T cell death. Information on
      the assembly, mechanistic and functional interactions at the immuno-viral
      synapses may well assist in elucidating new strategies to combat HIV infection.

PMID- 16786150
TI  - Specific subtelomere loss on chromosome der(11)t(3;11)(q23;q23)x2 in anaplastic
      thyroid cancer cell line OCUT-1.
AB  - One of the most aggressive human malignancies, anaplastic thyroid carcinoma
      (ATC), has an extremely poor prognosis that may be explained by its genomic
      instability. We hypothesized that the very rapid cell turnover observed in ATC
      might accelerate telomere shortening and chromosomal instability associated with
      tumor cell malignancy. To compare and measure chromosomal aberrations and
      telomere shortening in the anaplastic thyroid cancer cell line OCUT-1, we applied
      quantitative fluorescence in situ hybridization (Q-FISH) techniques. In all 15
      metaphases studied, telomere length estimates from Q-FISH of chromosomes in ATC
      were shorter than those of a fibroblast cell line derived from the stroma
      adjacent to the carcinoma. OCUT-1 cells display several chromosomal
      abnormalities, but have a near-normal chromosome complement of 46, XX, making it
      easy to analyze the karyotype. The karyotype showed 50, XX, +7, +11,
      der(11)t(3;11)(q23;q23)x2, del(12)(p11.2p12), +20, +1mar. We analyzed carefully
      the abnormalities in karyotype of OCUT-1 associated with telomere shortening on
      each chromosome and expression of subtelomeres. Telomere lengths in the q-arms of
      the abnormal chromosome del(12)(p11.2p12) were shorter than the average length in
      the q-arms of the normal chromosome 12 in OCUT-1. Subtelomeres on the abnormal
      chromosome der(11)t(3;11)(q23;q23)x2 also showed loss of signals on 11p, but
      there was no loss of signals in the cytogenetically normal trisomies 7 and 20 or
      the abnormal chromosome del(12)(p11.2p12). Subtelomeres of 3q had eight signals,
      one pair remaining in place on 3q and another pair on the abnormal 11p. Our
      findings suggest that telomere shortening and subtelomere loss are correlated
      with genetic instability in this anaplastic thyroid carcinoma cell line.

PMID- 16786151
TI  - Comano's (Trentino) thermal water interferes with the expression and secretion of
      vascular endothelial growth factor-A protein isoforms by cultured human psoriatic
      keratinocytes: a potential mechanism of its anti-psoriatic action.
AB  - Thermal balneotherapy with Comano spa's water (CW; Trentino, Italy) is used for
      psoriasis and other skin disorders but the mechanism(s) of action of this
      hypotonic water are unknown. Since skin psoriatic manifestations are thought to
      be angiogenesis-dependent, we assessed CW's effects on the expression and release
      of VEGF-A protein isoforms by cultured human lesional keratinocytes isolated from
      skin biopsies performed in 9 patients. Confluent, psoriatic keratinocytes were
      exposed for 11 days to DMEM, whose chemicals had been dissolved in either
      deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected
      by Western immunoblotting (WB), incubation in CW-DMEM elicited, with respect to
      DW-DMEM, an increase in intracellular and/or cell-bound L-VEGF-A189 and L-VEGF
      A165 48 kDa protein isoforms with no concurrent change in L-VEGF-A121 and L-VEGF
      A165 45 kDa proteins. Moreover, WB analysis of the secreted VEGF-A (sVEGF-A)
      proteins showed that the 20 and 15 kDa bands corresponding to different VEGF-A
      isoforms were directly and remarkably reduced in keratinocyte-conditioned CW-DMEM
      vs. DW-DMEM. Thus, CW interferes with VEGF-A isoform expression and secretion by
      the psoriatic keratinocytes. These effects would reduce all VEGF-A-mediated
      angiogenic, vessel permeabilising, and chemotactic effects, thereby at least in
      part explaining the beneficial actions of CW balneotherapy on the clinical
      manifestations of psoriasis.

PMID- 16786152
TI  - Mutational analysis of the NF2 gene in sporadic meningiomas by denaturing high
      performance liquid chromatography.
AB  - The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the
      development of sporadic meningiomas of the nervous system. In order to evaluate
      the role of the NF2 gene in sporadic meningiomas, we analyzed the entire coding
      regions of the NF2 gene in a group of 42 sporadic meningiomas: 17 meningothelial,
      11 transitional, 11 fibrous, one secretory, one atypical, and one malignant
      subtype, using denaturing high-performance liquid chromatography (DHPLC) and
      sequence analysis. Twenty-one mutations were identified in 20 patients with an
      overall mutation detection rate of 47.6%. The mutations included nine deletions
      (exons 1, 2, 5, 10, and 12), resulting in a frameshift, four non-sense mutations
      (exons 1, 2, and 7), four splice errors (exons 4, 5, 7, and 12), two missense
      mutations (exon 5) and two silent mutations (exon 11). Among these, 14 novel
      mutations were also identified in the present study. All mutations were noted in
      the first 12 exons, the region of homology with the ezrin-moesin-radixin protein.
      Furthermore, an association between NF2 mutations and histologic subtypes were
      observed; NF2 mutations were more frequent in fibrous meningiomas (8/11, 73%) and
      transitional meningiomas (6/11, 55%), than in meningothelial variant (5/17, 29%).
      These results provide evidence that mutations in the NF2 gene play an important
      role in the development of sporadic meningiomas as well as indicating a different
      tumorigenesis of these meningioma variants.

PMID- 16786153
TI  - PAR-1 upregulation by trimethyltin and lipopolysaccharide in cultured rat
      astrocytes.
AB  - We have previously shown that various protease-activated receptor (PAR) isoforms,
      mainly PAR-1, are upregulated in reactive astrocytes of rat hippocampus following
      i.p. administration of trimethyltin (TMT), a neurotoxicant which is known to
      cause neuronal death and reactive gliosis. In the present paper, we demonstrate
      that this PAR-1 upregulation was also mimicked in primary cultures of neonatal
      rat cortex astrocytes after exposure (24 and 48 h) to TMT (10-100 microM). This
      result suggests that the PAR-1 increase we have observed in vivo may represent a
      direct effect of TMT on astrocytes rather than a consequence of a complex
      astrocytic reaction following neuronal death. Furthermore, an evident
      upregulation of PAR-1 in cultured primary astrocytes also occurred following
      exposure to lipopolysaccharide (LPS) (a well-known inductor of glial cell
      activation) whereas other neurotoxic agents (such as staurosporine, hydrogen
      peroxide and sodium azide), which are known to induce cell death, were unable to
      determine any PAR-1 variation. Similarly to astrocytes, both TMT and LPS induced
      an upregulation of PAR-1 in the rat astrocytoma cell line, C6, thus indicating
      that this phenomenon was independent from microglial cells eventually
      contaminating astrocyte primary cultures. Furthermore, after exposure to TMT and
      LPS, the levels of tumor necrosis factor-alpha and interleukin-1beta were also
      increased in astrocyte cultures, suggesting that the PAR-1 upregulation we have
      detected may be involved in glial inflammatory response rather than in cell
      death.

PMID- 16786154
TI  - COX-2 inhibitors sensitize human hepatocellular carcinoma cells to TRAIL-induced
      apoptosis.
AB  - Cyclooxygenase (COX)-2 is upregulated in a variety of human cancers, including in
      hepatocellular carcinoma (HCC), whereas it is undetectable in most normal tissue.
      Evidence suggests that COX-2 is likely to be involved in hepatocarcinogenesis
      and, thus, COX-2 may be involved in an early process in carcinogenesis,
      dedifferentiation. To address this possibility, we investigated the effect of COX
      2 inhibitors on TNF-related apoptosis, inducing ligand (TRAIL) sensitivity and
      its molecular mechanisms, with special attention to anti-apoptotic proteins. We
      used the highly selective COX-2 inhibitors, NS398 and CAY10404. We also used the
      MTT assay and cytological analysis of DAPI-stained DNA to assess viability and
      apoptosis in two HCC cells (SK-Hep1 and HLE). In order to ask what led to
      increased sensitivity to TRAIL in HCC cells, cell surface expression of TRAIL and
      TRAIL-receptors was investigated using flow cytometry analysis. Expression of
      survivin, X-chromosome-linked IAP (XIAP), Bcl-xL, AKT and phospho-AKT was also
      investigated using immunoblotting. COX-2 inhibitors resulted in a concentration
      dependent decrease in cell viability in the two HCC cell lines tested. Subtoxic
      levels of COX-2 inhibitors did not significantly augment TNFalpha-induced
      apoptosis but did dramatically enhance TRAIL-induced apoptosis in both cell
      lines. TRAIL receptor 2/death receptor 5 (TRAIL-R2/DR5) expression was
      significantly up-regulated in SH-Hep1 and HLE cells. TRAIL receptor 1/death
      receptor 4 (TRAIL-R1/DR4) expression was up-regulated only in SK-Hep1. Expression
      of survivin and Bcl-xL was down-regulated in SK-Hep1 and HLE cells in the
      presence of CAY10404 but XIAP was not affected. Expression of survivin, Bcl-xL
      and XIAP was down-regulated in SK-Hep1 cells in the presence of NS398. Survivin
      expression was also down-regulated in the presence of NS398 in HLE cells.
      Finally, NS398 also decreased phospho-AKT in SK-Hep1 cells. These results
      demonstrate that COX-2 inhibitors can induce apoptosis and augment TRAIL
      sensitivity by up-regulation of TRAIL receptors and down-regulation of both
      survivin and AKT signaling.

PMID- 16786155
TI  - Neurotrophins and neurotransmitters in human palatine tonsils: an
      immunohistochemical and RT-PCR analysis.
AB  - Lymphoid organs are supplied by many nerve endings associated with different
      kinds of cells and macrophages. The role of these neuromediators on the release
      of locally active molecules is still unknown. Here we focused our attention on
      the expression of some neurotrophins (NTs), their high- and low-affinity
      receptors and several neurotransmitters in human palatine tonsils. Light and
      electron microscopy immunohistochemistry showed that human tonsillar samples were
      positive for all analyzed neurotrophins (NGF, BDNF and NT-3) and their high
      affinity receptors (TrkA, TrkB and TrkC, respectively). All of these molecules
      were strongly expressed in macrophages whereas, in some patients, a weaker
      specific staining of lymphocytes and blood vessels was also found. The low
      affinity receptor for NGF (p75) was always absent in the analysed samples. RT-PCR
      confirmed the occurrence of specific transcripts for NTs and their high-affinity
      receptors as well as the absence of mRNA for p75 protein. Also, specific
      immunoreactivity for neurotransmitters SP, VIP, CGRP, ChAT and nNOS was mainly
      expressed by macrophagic cells. These results suggest the presence of an
      extensive network of innervation in the human palatine tonsils which may play a
      role in the regulation of some immune functions as well as in the modulation of a
      possible functional scenario of interactions among different immune cellular
      subtypes.

PMID- 16786156
TI  - Heterozygous Thr 135 Ala polymorphism at leucine-rich repeat (LRR) in genomic DNA
      of toll-like receptor 4 in patients with poorly-differentiated gastric
      adenocarcinomas.
AB  - The genomic DNA of toll-like receptor (TLR) 2, TLR4, radioprotective 105, TLR6,
      and TLR9 were examined for mutations in 48 patients with gastric cancer. Of
      these, 22 had well-differentiated and 20 had poorly-differentiated
      adenocarcinomas, the latter group including 10 with signet ring cell carcinomas.
      The remaining 6 had gastric adenomas. Ten healthy volunteers with no family
      history of malignant diseases served as controls. DNA was extracted from
      peripheral blood and subjected to electrophoresis using PCR oligonucleotide
      primers. The resultant gel was analyzed with a DNA sequencer. None of the healthy
      volunteers, patients with gastric adenomas or those with well-differentiated
      gastric adenocarcinomas showed mutations. However, 8 of the 20 with poorly
      differentiated gastric adenocarcinoma showed heterozygosity at the 135th position
      of the amino acid sequence of TLR4, and a mutation from threonine to alanine was
      found at this site. Analysis of the entire available amino acid sequence of TLR4
      revealed that this mutation occurred at a leucine-rich repeat corresponding to
      one of its extracellular components. This suggests a disturbance in the protein
      phosphorylation reaction of TLR4, and that this disturbance is related to the
      development of poorly-differentiated gastric adenocarcinomas.

PMID- 16786157
TI  - Role of the carbohydrate recognition domains of mouse galectin-4 in
      oligosaccharide binding and epitope recognition and expression of galectin-4 and
      galectin-6 in mouse cells and tissues.
AB  - Galectin-4 and its homologue galectin-6 are members of the tandem-repeat
      subfamily of monomer divalent galectins. Expression of mouse galectin-4 and
      galectin-6 by RT-PCR using primers designed to distinguish both galectin
      transcripts indicates that both are expressed in the small intestine, colon,
      liver, kidney, spleen and heart and P19X1 cells while only galectin-4 is
      expressed in BW-5147 and 3T3 cell lines. In situ hybridization confirmed the
      presence of galectin-4/-6 transcripts in the liver and small intestine. Galectin
      4 is expressed in spermatozoons and oocytes and its expression during early mouse
      emryogenesis appears in 8-cell embryos and remains in later stages, as tested by
      RT-PCR. To study the role of carbohydrate recognition domains (CRDs) in
      oligosaccharide binding and epitope recognition, we cloned mouse full-length
      galectin-4 and galectin-6 cDNA and constructed bacterial expression vectors
      producing histidin-tagged recombinant galectin-4 and its truncated CRD1 and CRD2
      forms. Oligosaccharide binding profile for all recombinant forms was assessed
      using Glycan Array available through the Consortium for Functional Glycomics.
      Acquired data indicate that mGalectin-4 binds to alpha-GalNAc and alpha-Gal A and
      B type structures with or without fucose. While the CRD2 domain has a high
      specificity and affinity for A type-2 alpha-GalNAc structures, the CRD1 domain
      has a broader specificity in correlation to the total binding profile. These data
      suggest that CRD2 might be the dominant binding domain of mouse galectin-4.
      Mapping of epitopes reactive for biotinylated his-tagged CRD1, CRD2 and mGalectin
      4 performed on mouse cryosections showed that all three forms bind to alveolar
      macrophages, macrophages of red pulp of the spleen and proximal tubuli of the
      kidney and this binding was inhibited by 5 mM lactose. Interestingly, mGalectin
      4, but not CRD forms, binds to the suprabasal layer of squamous epithelium of the
      tongue, suggesting that the link region also plays an important role in ligand
      recognition.

PMID- 16786158
TI  - Cellular apoptosis susceptibility protein and proliferation in human
      hepatocellular carcinoma.
AB  - The cellular apoptosis susceptibility protein (CAS) is the human homologue of the
      product of the essential yeast chromosome segregation gene, CSE1, and has
      important roles in tumor necrosis factor (TNF)-induced apoptosis and cell
      proliferation. In this study, we used immunoblotting and immunohistochemistry to
      look at CAS expression in human hepatocellular carcinoma (HCC) cells. We also
      studied the correlation between CAS expression and cell proliferation. To do
      this, we studied the expression of proliferating cell nuclear antigen (PCNA) by
      immunostaining and at apoptosis by in situ nick end-labeling (TUNEL), followed by
      calculation of the PCNA labeling index (PCNA LI) and TUNEL labeling index (TUNEL
      LI). CAS was constitutively expressed in human HCC cell lines and was primarily
      confined to the cytoplasm of the cells. PCNA LI and TUNEL LI were significantly
      higher in HCC than in non-tumor tissue (p<0.01); however, the ratio of TUNEL
      LI/PCNA LI in HCC was significantly lower than that of non-tumor tissue.
      Immunohistochemistry revealed that the staining intensity score of CAS in HCC was
      significantly higher than that of non-tumor tissue (p<0.05). These results
      indicate that there is an augmentation of pro-liferative activity and apoptosis
      in HCC tissue, as compared to non-tumor tissue. There was a significant positive
      correlation between CAS and PCNA LI (p<0.05). In addition, we observed an inverse
      relationship between CAS expression and TUNEL LI, although the correlation did
      not reach statistical significance. These results suggest that CAS is expressed
      at higher levels in human HCC tissue than in non-tumor tissue. CAS may be
      associated with cell proliferation rather than apoptosis, and further, CAS might
      play an important role in the development of human HCCs.

PMID- 16786159
TI  - Dynamics of hyaluronan, CD44, and inflammatory cells in the rat kidney after
      ischemia/reperfusion injury.
AB  - Ischemia/reperfusion (I/R) injury in the kidney involves hemodynamic and cellular
      dysfunctions as well as leukocyte infiltration. Functional recovery occurs via
      cell proliferation and/or migration. To determine the roles of hyaluronan (HA)
      and its main receptor CD44 in renal postischemic processes, we compared their
      localization and expression with that of neutrophils, macrophages, and PCNA
      positive (regenerative) cells as characterized by immunohistochemistry, up to 28
      days after I/R in uninephrectomized rats. Observations covered all kidney zones,
      i.e. cortex (C), outer and inner stripes of outer medulla (OSOM, ISOM), and inner
      medulla (IM). In controls, HA was localized to the interstitium of IM and ISOM,
      and CD44 was mostly present on the basolateral membranes of collecting ducts in
      ISOM, the thin descending limb of Henle's loop and macula densa cells. After I/R,
      HA and CD44 staining appeared in C and OSOM at 12 h and persisted throughout the
      regenerative period, i.e. until day 7. Thereafter, they regressed but remained
      associated with remodeling areas. CD44 expression was found de novo on the apical
      pole of regenerating, not fully differentiated tubular cells and on some
      interstitial cells. It was prominent on all infiltrating neutrophils, as soon as
      2 h post-I/R, and on 30% of the macrophages, including those in late HA-rich
      inflammatory granulomas. CD44 is probably involved in early leukocyte
      infiltration, in tubular regeneration, and in macrophage activity, while HA
      modifies the physico-chemical environment of interstitial and migrating cells.
      Based on its presence in remodeling areas, the HA-CD44 pair may be implicated in
      persistent postichemic inflammation as observed in chronic allograft nephropathy.

PMID- 16786160
TI  - Regulation of calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1):
      review.
AB  - The response of living cells to change in cell environment depends on the action
      of second messenger molecules. The two second messenger molecules cAMP and Ca2+
      regulate a large number of eukaryotic cellular events. Calmodulin-stimulated
      cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in
      the complex interaction between cAMP and Ca2+ second messenger systems. Some PDE1
      isozymes have similar kinetic and immunological properties but are differentially
      regulated by Ca2+ and calmodulin. Accumulating evidence suggests that the
      activity of PDE1 is selectively regulated by cross-talk between Ca2+ and cAMP
      signalling pathways. These isozymes are also further distinguished by various
      pharmacological agents. We have demonstrated a potentially novel regulation of
      PDE1 by calpain. This study suggests that limited proteolysis by calpain could be
      an alternative mechanism for the activation of PDE1. We have also shown PDE1
      activity, expression and effect of calpain in the rat model in vitro of cardiac
      ischemia-reperfusion.

PMID- 16786161
TI  - Measurement of the radical scavenging activity of chicken jelly soup, a part of
      the medicated diet, 'Yakuzen', made from gelatin gel food 'Nikogori', using
      chemiluminescence and electron spin resonance methods.
AB  - We reported that gelatin gel 'Nikogori' soup made from the collagen in chicken
      wing meat, which is a part of the medicated diet 'Yakuzen', has high peroxyl and
      hydroxyl radical scavenging activities as the antioxidative capacity using
      chemiluminescence and electron spin resonance methods. The peroxyl radical
      scavenging activity of the soy sauce and chicken jelly 'Nikogori' soup sample was
      much higher than that of the chicken-only sample (control) at 100 degrees C
      heating for 60 min, although the addition of soy sauce only slightly enhanced the
      hydroxyl radical scavenging activity. Although the addition of garlic slightly
      enhanced the hydroxyl radical scavenging activity, it strongly inhibited the
      peroxyl radical scavenging activity. We found that chicken jelly 'Nikogori' soup
      only and soup with the addition of soy sauce had the highest antioxidative
      capacity as part of the medicated diet, 'Yakuzen'.

PMID- 16786162
TI  - Resistance to endoplasmic reticulum stress is an acquired cellular characteristic
      of rheumatoid synovial cells.
AB  - Synoviolin is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase which
      plays a critical role in ER-associated degradation (ERAD). We found that
      Synoviolin is a novel causative factor for rheumatoid arthritis (RA), which is
      especially up-regulated in proliferating synovial cells in the disease. We
      attempted to examine the role of Synoviolin in ER stress-induced apoptosis and
      proliferation of synovial cells. RA synovial cells (RSCs) were refractory to ER
      stress-induced apoptosis compared with HEK293 or HeLa cells. RSCs were also more
      resistant to the apoptosis than synovial cells from osteoarthritis patients,
      significantly. Down-regulation of Synoviolin by siRNA increased the
      susceptibility to ER stress-induced apoptosis in RSCs. Knock-down of Synoviolin
      by siRNA did not only induce apoptosis of RSCs but also inhibited their
      proliferation in vitro. These data suggest that RSCs are extraordinarily
      refractory to ER stress-induced apoptosis, and we termed this special property
      'hyper-ERAD'. Since Synoviolin is overexpressed in RSCs, and is known to play a
      critical role in the ERAD system as E3 ubiquitin ligase, hyper-ERAD is likely to
      present in these cells. Subsequently, the hyper-ERAD may cause synovial
      hyperplasia through its anti-apoptotic effect in RA. Further analyses are
      necessary to address this point, however, resistance to ER stress-induced
      apoptosis, or hyper-ERAD is a noteworthy new cellular characteristic of RSCs.

PMID- 16786163
TI  - Association of polymorphisms in forkhead box C2 and perilipin genes with bone
      mineral density in community-dwelling Japanese individuals.
AB  - Evidence suggests the existence of a close relation between lipid metabolism and
      bone remodeling. We hypothesized that polymorphisms of genes that play a role in
      lipid metabolism, such as those for forkhead box C2 (FOXC2) and perilipin (PLIN),
      might affect bone mineral density (BMD). We thus examined the possible
      relationships between a -512C --> T polymorphism of FOXC2 and a 1243C --> T
      polymorphism of PLIN to BMD in community-dwelling Japanese women and men. The
      subjects (1129 men, 1114 women for FOXC2; 1122 men, 1112 women for PLIN) were
      aged 40 to 79 years and were randomly recruited to a population-based prospective
      cohort study of aging and age-related diseases in Japan. Genotypes for FOXC2 and
      PLIN were determined with a fluorescence-based allele-specific DNA primer assay
      system. The -512C --> T polymorphism of FOXC2 was associated with BMD for the
      distal and proximal radius in men and in premenopausal women as well as with BMD
      for the distal radius and total body in postmenopausal women, with the T allele
      being related to reduced BMD. The 1243C --> T polymorphism of PLIN was associated
      with BMD for the total body, lumbar spine, femoral neck, and trochanter in men,
      with the C allele being related to reduced BMD. This polymorphism of PLIN was not
      associated with BMD in all women. These results suggest that FOXC2 is a
      susceptibility locus for reduced BMD in Japanese men and women, and that PLIN
      constitutes such a locus in Japanese men.

PMID- 16786164
TI  - Insulin-like growth factor I differentially regulates the expression of
      HIRF1/hCAF1 and BTG1 genes in human MCF-7 breast cancer cells.
AB  - Differential display PCR analysis (DD-PCR) was used to identify novel genes that
      respond to IGF-I treatment in human MCF-7 breast cancer cells. Fifty-three cDNAs
      showed alterations in their mRNA levels in IGF-I treated cells. One of these
      genes showed a significant increase in the mRNA level in IGF-I treated cells in
      comparison to non-treated cells. We named this gene HIRF1 (human IGF-I regulated
      factor 1). Nucleotide blast analysis revealed that this gene has a 100% sequence
      identity with the sequence for BTG1 (B-cell translocation gene) binding factor 1
      (human CCR4-associated factor 1 gene, hCAF1). By alignment of cloned HIRF1 cDNA
      and genomic DNA 8p21.3-p22 sequence, we were able to determine the exon-intron
      structure of the cloned HIRF1 gene on chromosome 8. Northern blot and real-time
      PCR analysis showed that BTG1 and c-fos reached their maximal expression fairly
      early within 10 min to 1 h, and decreased to basal levels after 3 h of IGF-I
      treatment. HIRF1/hCAF1 expression reached maximal stimulation after 3 h of IGF-I
      treatment and then gradually decreased to basal level. HIRF1 and BTG1 mRNA was
      inhibited by inhibitors of the cell signaling pathways, PI3/Akt kinase and MAPK
      kinases (ERK1/2 and p38). In summary, cloned HIRF1/hCAF1 is coregulated with BTG1
      in response to IGF-I. The regulation of these genes as early response genes may
      have an important role in differentiation, growth and proliferation of breast
      cancer cells.

PMID- 16786165
TI  - Metallic but not ceramic wear particles increase prostaglandin E2 release and
      interleukin-1beta gene expression in human blood monocytes in vitro.
AB  - In this study the potential of clinically relevant alumina ceramic and metal wear
      particles to induce an in vitro inflammatory response was assessed in human
      monocytes and lymphocytes isolated from healthy donors by measuring prostaglandin
      E2 (PGE2) levels and mRNA expression of various pro-inflammatory cytokines.
      Bacterial lipopolysaccharide (LPS) was used as positive control. LPS
      significantly increased PGE2 levels in the incubation medium of monocyte cultures
      after 24 h. Alumina had no effect on PGE2 production, whereas metals induced a
      concentration-dependent increase in PGE2 release, that was statistically
      significant at the dose of 0.1 mg/ml. In lymphocytes, LPS elicited a weak but
      significant increase in PGE2 release, whereas both alumina and metals did not
      modify PGE2 amounts at any of the concentrations tested. The gene expression of a
      number of pro- and anti-inflammatory cytokines was assessed in monocytes and
      lymphocytes exposed to LPS, 0.1 mg/ml alumina or 0.1 mg/ml metals for 24 h. In
      monocytes, LPS caused a 2-fold increase in interleukin-1beta (IL-1beta) mRNA
      levels. The exposure of monocytes to metals resulted in a selective increase in
      IL-1beta mRNA accumulation (+48% compared to control). By contrast, alumina did
      not modify IL-1beta mRNA levels. None of the test substances elicited any
      response on purified lymphocyte population. These findings suggest that PGE2
      production and IL-1 mRNA expression are a reliable marker to study the pro
      inflammatory effects of wear debris in vitro. The lower activity of alumina
      compared to metals suggests that the former should be preferred in implants for
      its favorable biological and mechanical behavior.

PMID- 16786166
TI  - Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation
      in 3T3-L1 cells.
AB  - Fucoxanthin is a major carotenoid found in edible seaweed such as Undaria
      pinnatifida and Hijikia fusiformis. We investigated the suppressive effects of
      fucoxanthin and its metabolite, fucoxanthinol, on the differentiation of 3T3-L1
      preadipocytes to adipocytes. Fucoxanthin inhibited intercellular lipid
      accumulation during adipocyte differentiation of 3T3-L1 cells. Furthermore,
      fucoxanthin was converted to fucoxanthinol in 3T3-L1 cells. Fucoxanthinol also
      exhibited suppressive effects on lipid accumulation and decreased glycerol-3
      phosphate dehydrogenase activity, an indicator of adipocyte differentiation. The
      suppressive effect of fucoxanthinol was stronger than that of fucoxanthin. In
      addition, in 3T3-L1 cells treated with fucoxanthin and fucoxanthinol, peroxisome
      proliferator-activated receptor gamma (PPARgamma), which regulates adipogenic
      gene expression, was down-regulated in a dose-dependent manner. These results
      suggest that fucoxanthin and fucoxanthinol inhibit the adipocyte differentiation
      of 3T3-L1 cells through down-regulation of PPARgamma. Fucoxanthinol had stronger
      suppressive effects than fucoxanthin on adipocyte differentiation in 3T3-L1
      cells.

PMID- 16786167
TI  - Expression pattern of matrix metalloproteinase and TIMP genes in fibroblasts
      derived from Ets-1 knock-out mice compared to wild-type mouse fibroblasts.
AB  - Matrix-degrading proteases play a key role in normal development, wound healing,
      many diseases such as rheumatoid arthritis and, in particular, tumour invasion.
      In invasive tumours, these enzymes are expressed by fibroblasts of the tumour
      stroma. Their expression and activity are tightly regulated at several levels, an
      important one being transcription. Previous in vitro and in vivo findings pointed
      to a major role of the Ets-1 transcription factor for this level of regulation.
      In the present study, we tried to prove this role in fibroblasts. We stimulated
      wild-type mouse fibroblasts with physiological doses of basic fibroblast growth
      factor (bFGF, known to induce different proteases and expressed by tumour cells)
      and compared the results to those obtained in Ets-1 -/- fibroblasts derived from
      Ets-1 knock-out mice. We found that basal Ets-1 levels are necessary not only for
      a fast induction of MMPs 2, 3 and 13 by bFGF but also for maintenance of the bFGF
      induced expression of tissue inhibitors of metalloproteinases (TIMPs) 1, 2 and 3,
      which are known not only to inhibit but also participate as activators of certain
      pro-MMPs.

PMID- 16786168
TI  - Activation of the ribosomal protein L13 gene in human gastrointestinal cancer.
AB  - Although ribosomal proteins are major components of ribosomes, recent data have
      shown them to have extraribosomal functions apart from ribosome and protein
      biosynthesis. In our earlier study, we showed that ribosomal protein L13 mRNA was
      up-regulated in response to DNA damage in hamster cells. We report here that L13
      expression is up-regulated in human gastrointestinal cancers. We also examined
      the biological role of L13 on human cancer cells. Knocking down L13 expression
      using small interfering RNA (siRNA) resulted in drastic attenuation of cancer
      cell growth with significant G1 and G2/M arrest of the cell cycle. Moreover, L13
      siRNA significantly enhanced the cellular sensitivity to certain DNA damaging
      agents and, concordantly, L13-overexpressing cells demonstrated greater
      chemoresistance compared to parent cells, suggesting an inverse correlation
      between L13 expression and chemosensitivity. By using semiquantitative RT-PCR, we
      analyzed expression of L13 in freshly resected cancer tissue of the stomach,
      colorectum and liver. Up-regulation of L13 mRNA expression was observed in 10
      (28%) of 36 gastric, 19 (41%) of 46 colorectal and 5 (20%) of 25 liver cancer
      tissue samples compared to adjacent normal tissue samples. We also found that
      increased expression of the L13 gene correlated with clinical staging in gastric
      cancers. The results of this study suggest that L13 plays an essential role in
      the progression of some gastrointestinal malignancies.

PMID- 16786169
TI  - Regucalcin increases Ca2+-ATPase activity in the heart mitochondria of normal and
      regucalcin transgenic rats.
AB  - The role of regucalcin, a regulatory protein in intracellular signaling system,
      in the regulation of Ca2+-ATPase activity in rat heart mitochondria was
      investigated. Mitochondrial Ca2+-ATPase activity was significantly increased by
      increasing concentrations of CaCl2 (2.5-50 microM). An increase in the enzyme
      activity was saturated at 50 microM CaCl2. The addition of regucalcin (10(-11)
      10(-8) M) in the enzyme reaction mixture caused a significant increase in Ca2+
      ATPase activity in heart mitochondria in the presence of 50 microM CaCl2.
      Regucalcin did not have a significant effect on mitochondrial Mg2+-ATPase
      activity. Regucalcin (10(-9) M) did not have a significant effect on Ca2+-ATPase
      activity in the presence of digitonin (10(-3) or 10(-2) %), which is a
      solubilization effect on membranous lipids. The effect of regucalcin in
      increasing mitochondrial Ca2+-ATPase activity was not observed in the presence of
      ruthenium red (10(-7) M) or lanthanum chloride (10(-7) M), which is an inhibitor
      of Ca2+ uniporter. The effect of regucalcin (10(-9) M) in increasing
      mitochondrial Ca2+-ATPase activity was not significantly enhanced in the presence
      of calmodulin (5 microg/ml) or dibutyryl cyclic AMP (10(-4) M), which is an
      intracellular signaling factor that can cause a significant increase in the
      enzyme activity. Mitochondrial regucalcin localization was significantly
      increased in the heart of regucalcin transgenic rats as compared with that of
      normal rats using Western blot analysis. Ca2+-ATPase activity was significantly
      increased in the heart mitochondria of regucalcin transgenic rats. This study
      demonstrates that regucalcin has an activating effect on Ca2+-ATPase in rat heart
      mitochondria, suggesting its role in the regulation of heart mitochondrial
      function.

PMID- 16786170
TI  - Mitochondria from the left heart ventricles of both normotensive and
      spontaneously hypertensive rats oxidize externally added NADH mostly via a novel
      malate/oxaloacetate shuttle as reconstructed in vitro.
AB  - A substantial increase in NADH production, arising from accelerated glycolysis,
      occurs in cardiac hypertrophy and this raises the question of how the NADH is
      oxidised. We have addressed this problem by reconstructing appropriate
      mitochondrial shuttles in vitro, using mitochondria from the left ventricles of
      both normotensive and spontaneously hypertensive rats at 5 and 24 weeks of age as
      model systems for left ventricle hypertrophy and hypertrophy/hypertension
      respectively. We found that most NADH oxidation occurs via a novel
      malate/oxaloacetate shuttle, the activity of which increases with time and with
      the progression of hypertrophy and development of hypertension as judged by
      statistical ANOVA analysis. In contrast, alpha-glycerol-phosphate and the
      malate/aspartate shuttles were shown to make only a minor contribution to NADH
      oxidation in a manner essentially independent of age and progression of
      hypertrophy/hypertension. The rate of malate transport in exchange with
      oxaloacetate proved to limit the rate of NADH oxidation via this
      malate/oxaloacetate shuttle.

PMID- 16786171
TI  - FK506 induces biphasic Ca2+ release from microsomal vesicles of rat pancreatic
      acinar cells.
AB  - The effect of the immunosuppressant drug FK506 on microsomal Ca2+ release was
      investigated in rat pancreatic acinar cells. When FK506 (0.1-200 microM) was
      added to the microsomal vesicles at a steady state of ATP-dependent 45Ca2+
      uptake, FK506 caused a dose-dependent and a biphasic release of 45Ca2+. Almost
      10% of total 45Ca2+ uptake was released at FK506 concentrations up to 10 microM
      (Km=0.47 microM), and 60% of total 45Ca2+ uptake was released at FK506
      concentrations over 10 microM (Km=55 microM). Preincubation of the vesicles with
      cyclic ADP-ribose (cADPR, 0.5 microM) increased the FK506 (< or =10 microM)
      induced 45Ca2+ release (Ozawa T, Biochim Biophys Acta 1693: 159-166, 2004).
      Preincubation with heparin (200 microg/ml) resulted in significant inhibition of
      the FK506 (30 microM)-induced 45Ca2+ release. Subsequent addition of inositol
      1,4,5-trisphosphate (IP3, 5 microM) after FK506 (100 microM)-induced 45Ca2+
      release did not cause any release of 45Ca2+. These results indicate that two
      types of FK506-induced Ca2+ release mechanism operate in the endoplasmic
      reticulum of rat pancreatic acinar cells: a high-affinity mechanism of Ca2+
      release, which involves activation of the ryanodine receptor, and a low-affinity
      mechanism of Ca2+ release, which involves activation of the IP3 receptor.

PMID- 16786172
TI  - Endothelin-1 activates Homer 1alpha expression via mitogen-activated protein
      kinase in cardiac myocytes.
AB  - Homer proteins are a family of scaffolding proteins which may play an important
      role in calcium signaling by facilitating the assembly of signaling complexes in
      neuronal cells. Among the three splice variants of Homer 1, Homer 1alpha is
      rapidly up-regulated by neural stimulation and may regulate the disassembly of
      signaling complexes mediated by Homer proteins. In spite of its potential
      importance in calcium signaling, the regulation of Homer 1alpha expression in
      cardiac myocytes has never been investigated. In this study, we examined the
      regulation of Homer 1alpha expression in cardiac myocytes. Homer 1alpha was
      significantly up-regulated by several hypertrophic agonists, including endothelin
      1 (ET-1), phenylephrine, isoprotenerol and angiotensin-II, and ET-1 most
      strikingly induced Homer 1alpha expression. The induction of Homer 1alpha
      expression by ET-1 peaked at 2 h and inhibitors for mitogen
      activated/extracellular signal regulated kinase (MEK) significantly suppressed
      the induction of Homer 1alpha. This study first clarified the regulation of Homer
      1alpha expression in cardiac myocytes and demonstrated that ET-1 induced Homer
      1alpha expression through the mitogen-activated protein kinase pathway.

PMID- 16786173
TI  - Effects of some endocrine disruptors on the secretory and proliferative activity
      of the regenerating rat adrenal cortex.
AB  - The effects of some endocrine disruptors that possess estrogen-like activity on
      the secretion and growth of regenerating rat adrenal cortex have been
      investigated in ovariectomized (OVX) and sham-OVX rats. As reference groups,
      dexamethasone (Dx)-administered sham-OVX and 17beta-estradiol-administered OVX
      animals were used. Dx, estradiol and endocrine disruptors were subcutaneously
      injected daily at a dose of 3 nmoles/100 g for 10 consecutive days after surgery,
      and adrenal enucleation was performed on day 5 of the experiment. Dx and
      genistein significantly decreased corticosterone plasma concentration (as
      measured by RIA) in sham-OVX rats with regenerating adrenals, while other
      disruptors (eusolex, procymidone, linurone, resveratrol, bisphenol-A and and
      silymarin) were ineffective. Mitotic index (as assayed by the stachmokinetic
      method with vincristine) was not changed by either Dx or disruptors. Estradiol
      significantly increased and genistein significantly lowered corticosterone blood
      level in OVX rats; similar effects were induced in the mitotic index of
      regenerating adrenals, but the changes were not significant. Eusolex increased
      the mitotic index, without altering the level of circulating corticosterone.
      Collectively, our findings allow us to conclude that, of the endocrine disruptors
      tested, only genistein is able to suppress the secretory activity of regenerating
      adrenal cortex, this Dx-like effect being apparently unrelated to its estrogen
      like activity, and only eusolex enhances the proliferation rate of regenerating
      adrenal, the effect being conceivably connected with its estrogen-like activity.

PMID- 16786174
TI  - Inhibition of cell cycle progression via p27Kip1 upregulation and apoptosis
      induction by an ethanol extract of Rhus verniciflua Stokes in AGS gastric cancer
      cells.
AB  - Botanical preparations are widely used by patient with cancer in Korea, Japan and
      China. Rhus verniciflua Stokes (RVS) has traditionally been used as a medicinal
      ingredient for the therapy of stomach and uterine cancer. In this study, we
      showed that exposure to an ethanol extract of RVS (50 microg/ml) resulted in a
      synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was
      related with the inhibition of proliferation and induction of apoptosis. The
      extract induces G1-cell cycle arrest through the regulation of cyclins, the
      induction of p27Kip1, and decrease the CDK2 kinase activity. The upregulated
      p27Kip1 level is caused by protein stability increment by the reduction of Skp2,
      a key molecule related with p27Kip1 ubiquitination and degradation, and de novo
      protein synthesis. RVS extract induces apoptosis through the expression of Bax,
      poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract
      induces G1-cell cycle arrest via accumulation of p27Kip1 controlled by Skp2
      reduction and apoptosis passing through an intrinsic pathway in human gastric
      cancer cells but not in normal cells, therefore we suggest that this extract
      could be a candidate medicine or compound for the development of novel class of
      anti-cancer drugs.

PMID- 16786175
TI  - Oxidized-HDL3 modulates the expression of Cox-2 in human endothelial cells.
AB  - Modified high density lipoprotein (HDL) has been suggested to modulate
      endothelial expression of proinflammatory genes. Since oxidised HDL (Ox-HDL) has
      been found in atheromatous plaques and receptors for modified HDL are present on
      endothelial cells, we investigated the effect of Ox-HDL3 on the expression of Cox
      1 or Cox-2. Ox-HDL3, increased Cox-2 mRNA and protein expression in endothelial
      cells while no effect on Cox-1 expression was observed. The intracellular
      pathways involved in this effect were investigated. The incubation with specific
      inhibitors of intracellular kinases showed that PI3K is mainly involved in the Ox
      HDL3-dependent Cox-2 induction. Transient transfection experiments suggested that
      the NF-IL6 response element in the proximal promoter (-327 to 59) is involved in
      Ox-HDL3-mediated Cox-2 expression. These data suggest that Ox-HDL induce Cox-2
      expression in endothelial cells through a PI3K/NF-IL6-dependent pathway.

PMID- 16786176
TI  - Tight junctions and compression therapy in chronic venous insufficiency.
AB  - Tight junctions (TJs) provide a barrier function, inhibiting solute and water
      flow through the paracellular space. There had been no analysis until now as to
      how tight junction molecules could be involved in the pathology of patients with
      chronic venous insufficiency. The aim of the study was to analyse the expression
      pattern of TJ-molecules occludin (OCLN), claudin-1 (CLDN-1), claudin-3 (CLDN-3)
      and claudin-5 (CLDN-5) on mRNA and protein level in patients with edema, venous
      leg ulcers and healthy controls. Biopsy specimens were taken in healthy
      individuals and in patients before, and four weeks after compression therapy.
      mRNA-expression was determined by using reverse-transcriptase and polymerase
      chain reaction (RT-PCR) and the protein-expression was determined by Western
      blotting from tissue specimens. Quantification performed determining the
      expression for TJ-molecules displayed diminished expression for CLDN-1 (p<0.01)
      and CLDN-5 (p<0.01) in patients with chronic venous insufficiency in comparison
      with healthy controls on mRNA as well as protein level. No statistical
      differences were detected for OCLN and CLDN-3 between the edema group and healthy
      controls. There was a significantly elevated expression (p<0.01) on mRNA and
      protein level between the leg ulcer group and healthy controls for OCLN and CLDN
      3. Densitometric evaluation revealed a more significantly elevated expression
      (p<0.01) for CLDN-1 and CLDN-5 on mRNA and protein level after four weeks of
      compression therapy in comparison with prior to treatment for the edema as well
      as the leg ulcer group. Compression therapy tightens the paracellular barrier via
      elevated expression of specific TJs and prevents thereby the progression of
      chronic venous insufficiency due to inhibited permeability of fluid into the
      perivascular tissue.

PMID- 16786177
TI  - Visual acuity comparison of vitrectomy with and without internal limiting
      membrane removal in the treatment of diabetic macular edema.
AB  - PURPOSE: To evaluate whether internal limiting membrane (ILM) peeling during
      vitrectomy affects vision outcome in patients with diabetic macular edema.
      MATERIAL AND METHOD: Fifty-eight eyes of 49 patients were included in the study.
      Patients with persistent diffuse clinically significant macular edema were
      divided into two groups according to the surgical method used. Group I subjects
      (15 patients; mean age 56.60+/-8.50 years; 17 eyes total) underwent vitrectomy
      with ILM peeling. Group II subjects (34 patients; mean age 57.52+/-11.54 years;
      41 eyes total) underwent vitrectomy without ILM peeling. The data recorded for
      each case were type and duration of diabetes, insulin treatment (yes/no),
      presence of arterial hypertension, stage of diabetic retinopathy, lens status,
      history of macular laser treatment, and detection of posterior vitreous
      detachment during surgery. Visual acuity was measured preoperatively and 1 year
      postoperatively in decimal notation, and values were converted to logarithm of
      minimal-angle-of-resolution (logMAR) scores. Mean pre- and postoperative visual
      acuity were compared within each group, and the mean change in visual acuity in
      Group I was compared to that in Group II. RESULTS: There were no significant
      differences between the groups with respect to age; sex distribution; diabetes
      type; duration of diabetes; numbers of patients on insulin treatment; frequencies
      of hypertension, proliferative diabetic retinopathy, previous macular laser
      treatment; or frequency of intraoperatively confirmed posterior vitreous
      detachment (chi-square, P>0.05 for all). Comparison of pre- and post-operative
      visual acuity revealed significant improvement in both Group I (1.15+/-0.307 vs.
      0.764+/-0.355 logMAR, respectively; Wilcoxon rank test, P<0.01) and Group II
      (1.22+/-0.516 vs. 0.829+/-0.436 logMAR, respectively; Wilcoxon rank test,
      P<0.001). The change in visual acuity for Group I was not significantly different
      from that observed in Group II (0.391+/-0.335 vs. 0.393+/-0.273 logMAR,
      respectively; Mann-Whitney U test, P>0.05). CONCLUSION: The visual acuity
      outcomes in the study indicate that vitrectomy without ILM peeling is just as
      effective as vitrectomy with ILM peeling in the treatment of diabetic macular
      edema. Both techniques led to significant and similar degrees of improvement in
      visual acuity.

PMID- 16786178
TI  - The irvine prism test: does the positive response indicate suppression scotoma?
AB  - PURPOSE: To investigate whether the positive prism test response is due to the
      presence of a suppression scotoma or the absence of bifoveolar fixation. METHODS:
      Fifty-one subjects with esotropia (microtropia, small-, moderate- or large-angle
      esotropia), and 22 subjects with nonstrabismic anisometropic amblyopia were
      examined. The prism test was performed by using base-out prisms of two different
      powers (4-PD and 30-PD), and base-in prism of 20-PD, as well as base-down prism
      of 10-PD for each subject. RESULTS: All the subjects with esotropia showed a
      positive prism test response, whereas all the subjects with nonstrabismic
      anisometropic amblyopia had a negative prism test response. All the esotropic
      subjects showed positive response to all magnitudes and positions of the prisms
      tested. CONCLUSIONS: The positive response to the prism test does not indicate
      suppression scotoma in subjects with microtropia and small-angle esotropia
      because all the esotropic subjects showed the positive response regardless of the
      amount of deviation or the sensorial adaptation mechanisms. Also, the positive
      response, seen in the esotropic subjects, did not alter to negative by using the
      prisms of different powers and directions.

PMID- 16786179
TI  - Late-stage diffuse unilateral subacute neuroretinitis: photocoagulation of the
      worm does not improve the visual acuity of affected patients.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the visual outcome following direct laser
      photocoagulation of the worm in patients with late-stage diffuse unilateral
      subacute neuroretinitis (DUSN). PATIENTS AND METHODS: The study reports on 22
      DUSN patients diagnosed in its late stage, in whom the worm was identified and
      subsequently destroyed by laser photocoagulation. Information gathered included
      initial and final visual acuities and length of follow-up. Statistical analysis
      was performed with the Paired Student's t-Test. A p value of less than 0.05 was
      considered significant. RESULTS: After a mean follow-up of 13.1 months, visual
      acuity improved in 2 patients, remained unchanged in 19 patients and decreased in
      one patient. Comparison of the visual outcome before and after laser treatment
      was not statistically significant (p = 0.302). CONCLUSION: Destruction of the
      worm by laser photocoagulation in eyes with late-stage DUSN does not improve the
      visual acuity of affected patients.

PMID- 16786180
TI  - When do tissues and cells become products? Regulatory oversight of emerging
      biological therapies.
AB  - Although therapeutics derived from biological sources have been subjected to
      regulatory oversight for some time, the products used in transplantation
      procedures have historically been exempt from this oversight. These products have
      been viewed as being part of medical practice rather than as the result of
      mainstream pharmaceutical manufacture. Furthermore, their unique source makes
      them difficult to assess in traditional regulatory systems based on the tenets of
      pharmaceutical quality control. With the increasing use of transplantation
      therapies to both replace dysfunctional organs and to influence genetic and
      metabolic processes, public health concerns on these therapies have increased. In
      addition, it is recognized that therapeutic claims for some of these
      interventions need to be properly assessed. These considerations have led the
      established regulatory agencies of the developed world to develop new regulatory
      paradigms for the products of transplantation practice. While a number of
      concerns have driven these developments, the minimization of infectious disease
      risk remains the paramount driver for introducing these regulatory systems. More
      than the regulation of medicines and medical devices manufactured in traditional
      pharmaceutical modes, the regulation of cell and tissue products is intimately
      linked to areas of public health policy and funding. This places regulators in a
      challenging position as they attempt to reconcile their roles as independent
      assessors with the needs of the overall public health framework. This is
      particularly difficult when considering measures which may affect access to life
      saving therapies. Regulators have recognized the need to assess these therapies
      through systems which incorporate consideration of risk-benefit ratios and
      include mechanisms for transparent and accountable release of products when full
      compliance to traditional concepts of manufacturing practice is not possible.

PMID- 16786181
TI  - [Diagnosis and therapy of dry eye syndrome].

PMID- 16786182
TI  - [Unilateral glaucoma with widened episcleral veins].

PMID- 16786183
TI  - [Intraocular pressure and corneal thickness. A comparison between non-contact
      tonometry and applanation tonometry].
AB  - OBJECTIVE: Corneal thickness and deformation seem to have a considerable
      influence on intraocular pressure measurement. Due to differences in the corneal
      deformation in either non-contact tonometry or applanation tonometry, both
      methods should be compared in the same patient group depending on central corneal
      thickness. METHODS: In 106 eyes of 55 patients (18 males, 37 females, age 17-89
      years, mean 63.3 years) with glaucoma and central corneal thickness between 409
      and 644 microm (Orbscan II pachymetry) intraocular pressure was measured in each
      eye with non-contact tonometry (Reichert AT550) and 30 min later with Goldman
      applanation tonometry. RESULT: Non-contact tonometry as well as applanation
      tonometry showed a positive correlation between measured intraocular pressure and
      corneal thickness. The steepness of the line of regression was 0.33 mmHg per 10
      microm of corneal thickness in non-contact tonometry and 0.17 mmHg per 10 microm
      of corneal thickness in applanation tonometry. CONCLUSION: Independently of the
      large differences in individual pressure measurements between non-contact
      tonometry and applanation tonometry, we found higher IOP values with non-contact
      tonometry in thicker corneas as compared with applanation tonometry. In thinner
      corneas there was a better correspondence between both methods. Thus, it seems
      very likely that corneal rigidity increases with corneal thickness.

PMID- 16786184
TI  - [Pain drawings of patients with orofacial pain. Comparison of acceptance and gain
      of information].
AB  - AIM OF THE STUDY: The aim of this prospective multicentric study was to compare
      two different types of pain drawings in terms of acceptance and gain of
      information in patients with orofacial pain. PATIENTS AND METHODS: A total of 204
      patients from 9 centers, who visited their dentist or physician for orofacial
      pain, received two different diagrams for pain drawings in random order. One was
      the original pain diagram of the Deutsche Schmerzfragebogen (German Pain
      Questionnaire, diagram A), and the other diagram had been developed to achieve a
      symmetrical representation of the body and to allow computer-assisted analysis
      (diagram B). This diagram was larger and contained a drawing of the head. The
      patients' answers were analyzed for the preference between diagrams, the number
      and distribution of pain areas, and the concordance between the diagrams. The
      results were correlated with the patients' data. RESULTS: Data from 183 patients
      could be analyzed: 100 of 183 patients preferred diagram B and 57 of 183
      preferred diagram A, independent of gender, age, or duration of disease. Most
      patients reported pain in more than one area; in only 43 of 183 patients was the
      pain limited to the face and head. The number and distribution of pain areas were
      not different between the two pain diagrams. CONCLUSIONS: Detailed head and body
      diagrams can be used in the diagnostic evaluation of patients with orofacial pain
      without fear of placing excessive demands on the patients and are useful for
      detecting comorbidities.

PMID- 16786186
TI  - Rutin improves the antioxidant status in streptozotocin-induced diabetic rat
      tissues.
AB  - Rutin, a polyphenolic flavonoid, was investigated for its antioxidant potential
      in streptozotocin (STZ)-induced diabetic rats. Rats were rendered diabetic by a
      single intraperitoneal injection of streptozotocin (50 mg/kg). The levels of
      fasting plasma glucose and insulin were estimated. Lipid peroxidative products
      and antioxidants were estimated in liver, kidney and brain. Histopathological
      studies were carried out in these tissues. A significant (p < 0.05) increase in
      the levels of fasting plasma glucose, lipid peroxidative products (thiobarbituric
      acid reactive substances [TBARS] and lipid hydroperoxides [HP]) and a significant
      (p < 0.05) decrease in plasma insulin, enzymic antioxidants (superoxide dismutase
      [SOD], catalase, glutathione peroxidase [GPx] and glutathione reductase [GRx])
      and nonenzymic antioxidants (reduced glutathione [GSH], vitamin C and E) in
      diabetic liver, kidney and brain were observed. Oral administration of rutin (100
      mg/kg) for a period of 45 days significantly (p < 0.05) decreased fasting plasma
      glucose, increased insulin levels and improved the antioxidant status of diabetic
      rats by decreasing lipid peroxidative products and increasing enzymic and
      nonenzymic antioxidants. Normal rats treated with rutin (100 mg/kg) showed no
      significant (p < 0.05) effect on any of the parameters studied. Histopathological
      studies of the liver, kidney and brain showed the protective role of rutin. Thus,
      our study clearly shows that rutin has antioxidant effect in STZ-induced
      experimental diabetes.

PMID- 16786185
TI  - Adriamycin induced myocardial failure in rats: protective role of Centella
      asiatica.
AB  - Generation of reactive oxygen species and mitochondrial dysfunction has been
      implicated in adriamycin induced cardiotoxicity. Mitochondrial dysfunction is
      characterized by the accumulation of oxidized lipids, proteins and DNA, leading
      to disorganization of mitochondrial structure and systolic failure. The present
      study was aimed to evaluate the efficacy of Centella asiatica on the
      mitochondrial enzymes; mitochondrial antioxidant status in adriamycin induced
      myocardial injury. Adriamycin (2.5 mg/kg body wt., i.p.) induced mitochondrial
      damage in rats was assessed in terms of decreased activities (p<0.05) of cardiac
      marker enzymes (lactate dehydrogenase, creatine phosphokinase, amino
      transferases), TCA cycle enzymes (isocitrate dehydrogenase, alpha-ketoglutarate
      dehydrogenase, malate dehydrogenase, respiratory marker enzymes (NADH
      dehydrogenase, cytochrome-C-oxidase), mitochondrial antioxidant enzymes (GPx,
      GSH, SOD,CAT) and increased (p<0.05) level of lipid peroxidation. Mitochondrial
      damage was confirmed by transmission electron microscopic examination. Pre-co
      treatment with aqueous extract of Centella asiatica (200 mg/kg body wt, oral)
      effectively counteracted the alterations in mitochondrial enzymes and
      mitochondrial defense system. In addition, transmission electron microscopy study
      confirms the restoration of cellular normalcy and accredits the cytoprotective
      role of Centella asiatica against adriamycin induced myocardial injury. Our
      results demonstrated elevated oxidative stress and mitochondrial dysfunction in
      adriamycin treated rats. Moreover, on the basis of our findings it may be
      concluded that the aqueous extract of C. asiatica not only possesses antioxidant
      properties but it may also reduce the extent of mitochondrial damage.

PMID- 16786187
TI  - The roles of translation initiation regulation in ultraviolet light-induced
      apoptosis.
AB  - Ultraviolet light (UV) inhibits translation initiation through activation of
      kinases that phosphorylate the alpha-subunit of eukaryotic initiation factor 2
      (eIF2alpha). Two eIF2alpha kinases, PERK and GCN2, are known to phosphorylate the
      Serine-51 of eIF2alpha in response to UV-irradiation. In this report, we present
      evidence that phosphorylation of eIF2alpha plays a role in UV-induced apoptosis.
      Our data show that wild-type mouse embryo fibroblasts (MEF(s/s)) are less
      sensitive to UV-induced apoptosis than MEF(A/A) cells in which the
      phosphorylation site, Ser51, of eIF2alpha is replaced with a non-phosphorylatable
      Ala (Ser51Ala). PARP expression in MEF(A/A) cells is reduced without being
      cleaved after UV-irradiation. In contrast, PARP is cleaved without a significant
      decrease in parental PARP in MEF(S/S) cells after UV-irradiation. Our data also
      show that MEF(GCN2-/-) cells, in which GCN2 is knocked out, are more sensitive to
      UV-irradiation, agreeing with the observation from MEF(A/A) cells. However,
      MEF(PERK-/-) cells, in which PERK is knocked out, are less sensitive to UV
      irradiation. In addition, MCF-7-PERKDeltaC cells, which are stably transfected
      with a kinase domain deleted mutant of PERK (PERKDeltaC), are more resistant to
      UV-induced apoptosis than parental MCF-7 cells. Overexpression of wild-type PERK
      sensitizes MCF-7 cells to UV-induced apoptosis without directly inducing cell
      death. These results suggest that the level of eIF2alpha phosphorylation impacts
      PARP expression upon UV-irradiation. The eIF2alpha kinases may mediate UV-induced
      apoptosis via an eIF2alpha dependent or independent signaling pathway.

PMID- 16786188
TI  - Essential roles of ERKs and p38K in up-regulation of GST A1 expression by Maotai
      content in human hepatoma cell line Hep3B.
AB  - It is widely accepted that the consumption of alcohol may lead to hepatic
      injuries such as hepatic fibrosis and cirrhosis. However, consumption of Maotai,
      one of the famous liquors in China, is found to have no obvious relevance with
      hepatic injury as ordinary white wine does in both epidemiological and
      histopathological studies. Present study used human hepatoma cell line Hep3B to
      address the mechanisms involved in the resistance of alcohol-induced hepatic
      injury by Maotai liquor. We found that exposure of Hep3B cells to Maotai residue
      without ethanol (MRWE) resulted in the increased GST A1 anti-oxidant responsive
      element (ARE) transcriptional expression, while MRWE treatment did not affect Nrf
      2-dependent transcriptional activity. Those findings were further confirmed at
      all time points and doses tested, suggesting that GST A1 transcription was
      regulated by MRWE via an Nrf-2-independent pathway. Consistent with GST A1
      induction, the phosphorylation of c-Jun, extracellular signal-regulated kinases
      (ERKs) and p38 kinase (p38 K), were also observed in MRWE-treated Hep3B cells.
      Furthermore, pretreatment of cells with either PD98059 (an inhibitor specific for
      MEK1/2-ERKs pathway) or SB202190 (an inhibitor specific for p38 K) led to a
      significant decrease in the induction of GST A1 transcriptional expression by
      MRWE treatment. Our results indicate that certain content in MRWE is able to
      induce GST A1 ARE transcriptional expression, which may provide protective
      effects for hepatic cells by antagonizing the oxidative stress derived from
      ethanol via an ERKs- and p38 K-dependent pathway.

PMID- 16786189
TI  - Mutational analysis on the function of the SWAP-70 PH domain.
AB  - SWAP-70 is a phosphatidylinositol trisphosphate (PtdIns(3,4,5)P(3))-binding
      protein, which is suggested to be involved in membrane ruffling, cooperating with
      activated Rac. Various point mutations were introduced in the PH domain.
      Substitutions of alanines for the positively charged amino acids within the first
      loop abolished the binding activity of the PH domains to PtdIns(3,4,5)P(3). The
      PtdIns(3,4,5)P(3) binding activity was required for translocation of SWAP-70 to
      the membrane, enhancement of membrane ruffling by the overexpressed protein, or
      the dominant-negative effect of a mutant lacking the carboxyl terminal region in
      membrane ruffling. When Rac was overexpressed, the above mutants were
      translocated to the membrane and exhibited a dominant-negative effect on membrane
      ruffling without PtdIns(3,4,5)P(3)-binding activity. These results suggest that
      the PtdIns(3,4,5)P(3)-binding activity is dispensable for these events when SWAP
      70 and Rac interacts efficiently. These results implicate that binding of SWAP-70
      to PtdIns(3,4,5)P(3) may facilitate the recruitment of SWAP-70 to activated Rac.

PMID- 16786190
TI  - Identification, regulation and anti-proliferative role of the NPR-C receptor in
      gastric epithelial cells.
AB  - Evidence suggests that functional atrial natriuretic peptide (ANP) receptors
      occur in surface gastric mucosal epithelial cells. To evaluate functional aspects
      of ANP in a model of these cells we examined the expression of natriuretic
      peptide receptors (NPR) subtypes A and C in the non-transformed rat gastric
      mucosal epithelial cell line RGM1. Transcripts for NPR-A and NPR-C were detected
      in RGM1 cells by RT-PCR. However, only NPR-C protein was detected by Western blot
      and immunohistochemical analyses. Specific saturable binding of (125)I-ANP to
      RGM1 cells revealed a single class of high affinity binding sites (K (d) = 208 +/
      71pM, B (max) = 110,000 +/- 14,000 sites/cell, Hill coefficient = 0.97 +/-
      0.05). ANP (IC(50) 130 +/- 47pM), BNP (IC(50) 716 +/- 26 pM), CNP (IC(50) 356 +/-
      85pM) and C-ANP (IC(50) 134 +/- 13pM), a specific ligand for NPR-C, effectively
      displaced (125)I-ANP binding. Cross-linking of (125)I-ANP to cells labeled
      predominantly a protein of 66,000 Da. These data suggest that (125)I-ANP binding
      was primarily to NPR-C. ANP and C-ANP inhibited forskolin- and prostaglandin E(2)
      (PGE(2))-stimulated cAMP in a PTx-sensitive fashion. PGE(2), transforming growth
      factor-+/-1 (TGF-+/-1), forskolin, 8-bromo-cyclic AMP, and phorbol-12-myristate
      13-acetate (PMA) caused a dose-dependent decrease in specific (125)I-ANP binding,
      whereas epidermal growth factor (EGF), 8-bromo-cyclic GMP and 4+/--phorbol
      didecanoate had no effect. PGE(2), forskolin, TGF-+/-1 and PMA significantly
      decreased (125)I-ANP B (max) values, NPR-C protein and steady-state NPR-C
      transcript levels. H89, a protein kinase A inhibitor, blocked the reduction of
      NPR-C mRNA produced by both forskolin and PGE(2.) GF109203X, a protein kinase C
      inhibitor, abolished the PMA-induced decrease in NPR-C transcripts but only
      partially blocked that produced by TGF-+/-1. RGM1 cells exhibited a dose
      dependent decrease in both DNA synthesis and cell proliferation when cultured in
      the presence of ANP or C-ANP. These findings indicate that RGM1 cells express
      functional NPR-C receptors that can influence RGM1 cell proliferation and are
      down-regulated by PGE(2) and TGF-+/-1.

PMID- 16786191
TI  - BRD2 is one of BRD7-interacting proteins and its over-expression could initiate
      apoptosis.
AB  - BRD7 is a potential nuclear transcription regulation factor related to
      nasopharyngeal carcinoma (NPC). BRD2, a putative BRD7-interacting protein, has
      been screened from human fetal brain cDNA library by yeast two-hybrid system.
      This study was to further identify the interaction between BRD7 and BRD2 in
      mammalian cells, and to investigate the subcellular localization of BRD2, as well
      as the effect on the functions of cell biology. Both immunoprecipitation and
      subcellular colocalization were performed together to identify the interaction of
      BRD7 with full-length BRD2, as well as C-terminal truncated BRD2 or N-terminal
      truncated BRD2. GFP direct fluorescence and Hochest 33258 staining were used to
      investigate the cellular localization pattern of BRD2 and the roles in initiating
      cell apoptosis in COS7 and HNE1. The results showed that BRD7 could interact with
      BRD2 and the region from amino acid 430 to 798 of BRD2 was critical for the
      interaction of BRD2 with BRD7. BRD2 mainly localizes in nucleus in two
      distribution patterns, diffused and dotted, and BRD2 has distinct roles in
      initiating apoptosis, and the dotted distribution pattern of BRD2 in nucleus may
      be a morphologic marker of cell apoptosis.

PMID- 16786192
TI  - Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia
      reperfusion injury in rats.
AB  - There is a great evidence that reactive oxygen species (ROS) play an important
      role in the pathophysiology of ischemia-reperfusion (I/R) injury in skeletal
      muscle. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis.
      It has antioxidant, anti-inflammatory and free radical scavenger properties. The
      aim of this study is to determine the protective effects of CAPE against I/R
      injury in respect of protein oxidation, neutrophil in filtration, and the
      activities of xanthine oxidase (XO) and adenosine deaminase (AD) on an in vivo
      model of skeletal muscle I/R injury. Rats were divided into three equal groups
      each consisting of six rats: Sham operation, I/R, and I/R plus CAPE (I/R+CAPE)
      groups. CAPE was administered intraperitoneally 60 min before the beginning of
      the reperfusion. At the end of experimental procedure, blood and gastrocnemius
      muscle tissues were used for biochemical analyses. Tissue protein carbonyl (PC)
      levels and the activities of XO, myeloperoxidase (MPO) and AD in I/R group were
      significantly higher than that of control (p < 0.01, p < 0.05, p < 0.01, p <
      0.005, respectively). Administration of CAPE significantly decreased tissue PC
      levels, MPO and XO activities in skeletal muscle compared to I/R group (p < 0.01,
      p < 0.05, p < 0.05, respectively). In addition, plasma creatine phosphokinase
      (CPK), XO and AD activities were decreased in I/R+CAPE group compared to I/R
      group (p < 0.05, p < 0.05, p < 0.001). The results of this study revealed that
      free radical attacks may play an important role in the pathogenesis of skeletal
      muscle I/R injury. Also, the potent free radical scavenger compound, CAPE, may
      have protective potential in this process. Therefore, it can be speculated that
      CAPE or other antioxidant agents may be useful in the treatment of I/R injury as
      well as diffused traumatic injury of skeletal muscle.

PMID- 16786193
TI  - Expression and distribution of trihydrophobin 1 in postnatal developing mouse
      testis.
AB  - The human trihydrophobin 1 (TH1) is a highly conserved and widely expressed
      protein. It is clear that TH1 serves as a new specific negative regulator of A
      Raf kinase. In this study, we found that TH1 associated with A-Raf in mouse
      testis by using coimmunoprecipitation analysis. Then we characterized the gene
      expression of TH1 in mouse testis and analyzed the changes of TH1 protein during
      postnatal development. The protein expression of TH1 in mouse testis was further
      analyzed by immunohistochemistry staining. Strong signals were detected in the
      seminiferous tubules and the distribution patterns varied with the different ages
      of postnatal mouse testis. TH1 was distributed in spermatocytes and Sertoli cells
      at 2 weeks postnatal, and was abundant in spermatogonia at 8 weeks postnatal.
      Leydig cells were positive to TH1 throughout testicular development. A high
      expression of TH1 in both Leydig cells and mouse Leydig tumor cells (mLTC-1cells)
      was found to be concentrated in the cytoplasm. The colocalization of TH1 and A
      Raf in mLTC-1 cells or in adult testis was also observable.

PMID- 16786195
TI  - Differential expression changes in K562 cells during the hemin-induced erythroid
      differentiation and the phorbol myristate acetate (PMA)-induced megakaryocytic
      differentiation.
AB  - K562 cell line has been used as a model of common progenitor of erythroblasts and
      magakaryocytes and can be differentiated into erythroid and megakaryocytic
      lineages by hemin and phorbol myristate acetate (PMA) respectively. We analyzed
      mRNA expression in un-induced, hemin-induced and PMA-induced K562 cells by
      differential display reverse transcription polymerase chain reaction (DDRT-PCR)
      method. 314 differential expression sequence tags (ESTs) were obtained. Among
      them, 201 ESTs displayed up-regulation and 85 ESTs down-regulation after hemin
      induction, 186 ESTs showed up-regulation and 72 ESTs down-regulation after PMA
      induction. The differentially expressed genes included those encoding
      transcription factors, signaling factors, apoptosis-associated factors and
      others. 45 of these ESTs stand for genes whose open reading frames were found but
      whose functions remain unknown. 4 ESTs represent possibly new genes. Furthermore
      we compared differences of gene expression during hemin-induced erythroid
      differentiation and PMA-induced megakaryocytic differentiation and found that the
      expressional changes of some transcription factors and metabolism proteins are
      the common but the expressional changes of some signal pathways in these two
      differentiation processes are different. These results suggested that erythroid
      differentiation and megakaryocytic differentiation are associated in activation
      and repression of different signal pathways.

PMID- 16786194
TI  - TNF-alpha, IFN-gamma, and IL-1beta modulate hyaluronan synthase expression in
      human skin fibroblasts: synergistic effect by concomital treatment with FeSO4
      plus ascorbate.
AB  - Several reports have shown that a number of cytokines such as tumor necrosis
      alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-beta (IL-1beta)
      are capable to induce hyaluronan sinthases (HASs) mRNA expression in different
      cell culture types. The obvious consequence of this stimulation is a marked
      increment in hyaluronan (HA) production. It has been also reported that oxidative
      stress, by itself, may increase HA levels. The aim of this study was to evaluate
      how TNF-alpha, IFN-gamma,IL-1beta, and exposition to oxidative stress may
      modulate HAS activities in normal human skin fibroblasts. Moreover, the effects
      on HAS mRNA expression of the concomitant treatment with cytokines and oxidants,
      and the HA concentrations after treatments, were studied. TNF-alpha, IFN-gamma,
      and IL-1beta were added to normal or/and exposed to FeSO(4) plus ascorbate
      fibroblast cultures and HAS1, HAS2 and HAS3 mRNA content, by PCR-real time, was
      assayed 3,h later. HA levels were also evaluated after 24,h incubation. The
      treatment of fibroblasts with cytokines up-regulated HASs gene expression and
      increased HA production. IL-1beta induced HAS mRNA expression and HA production
      more efficiently than TNF-alpha and IFN-gamma. The exposition of the fibroblasts
      with the oxidant system markedly increased HAS activities while slightly HA
      production. The concomitant treatment of cells with the cytokines and the oxidant
      was able to further enhance, in a dose dependent way, with synergistic effect on
      HAS mRNA expression. On the contrary HA levels resulted unaffected by the
      concomitant treatment, and resemble those obtained with the exposure to FeSO(4)
      plus ascorbate only. This lack in HA production could be due to the deleterious
      action of free radicals on the HA synthesis.

PMID- 16786196
TI  - Identification of USF2 as a key regulator of Runx2 expression in mouse
      pluripotent mesenchymal D1 cells.
AB  - Runx2 is one of the most important transcription factors directing the
      osteogenesis of mesenchymal stem cells and osteoblastic functions. It is likely
      that the factors controlling Runx2 expression would trigger the early steps of
      osteoblast differentiation. By using a reporter gene assay for 4.5 kb Runx2
      promoter, it was found that the first 305 bp of Runx2 promoter are active in D1
      cells. Within this region, electromobility shift assays (EMSAs) delineated a 6 bp
      of CACATG bound specifically by the proteins from D1 cell nuclear extract.
      Antibody super-shift and DNA-coupling magnetic bead pull-down assay indicated
      that the protein bound to this sequence is USF2. Site-specific mutagenesis
      revealed that this sequence contributed to the activity of 305 bp Runx2 promoter.
      Thus, we suggest that USF2 might be one of the regulators for the expression of
      the Runx2 gene in D1 cells.

PMID- 16786198
TI  - Instability and dynamics of thin viscoelastic liquid films.
AB  - The instability, rupture, and subsequent growth of holes in a thin Jeffreys-type
      viscoelastic film under the influence of long-range van der Waals force are
      investigated using both linear stability analysis and nonlinear numerical
      solutions. The linear stability analysis of full governing equations valid for
      arbitrary wave numbers shows that although fluid rheology does not influence the
      dominant length scale of the instability, it significantly affects the growth
      rate. It is shown that neglect of inertia and solvent dynamics results in a
      nonphysical singularity in the growth rate beyond a critical value of relaxation
      time. We further carry out numerical simulations of a set of long-wave, nonlinear
      differential equations (also derived in Rauscher et al., Eur. Phys. J. E 17, 373
      (2005)) governing the evolution of the free surface. The nonlinear simulations,
      in their domain of validity, confirm the results of the linear analysis.
      Interestingly, results from nonlinear simulations further show that both for
      Newtonian and viscoelastic liquids, the shape and the dewetting dynamics of a
      hole are identical when examined in terms of a rescaled time which depends on
      rheological parameters. Thus, viscoelasticity of Jeffreys type merely accelerates
      the growth rate, without however affecting the important morphological
      characteristics.

PMID- 16786197
TI  - Cell surface beta 1, 4-galactosyltransferase 1 promotes apoptosis by inhibiting
      epidermal growth factor receptor pathway.
AB  - Our previous studies have shown that overexpression of beta1,4
      galactosyltransferase1 (beta1,4GT1) leads to increased apoptosis induced by
      cycloheximide (CHX) in SMMC-7721 human hepatocarcinoma cells. However, the role
      of beta1,4GT1 in apoptosis remains unclear. Here we demonstrated that cell
      surface beta1,4GT1 inhibited the autophosphorylation of epidermal growth factor
      receptor (EGFR) especially at Try 1068. The phosphorylation of protein kinase B
      (PKB/Akt) and extracellular signal-regulated protein kinase1/2 (ERK1/2), which
      are downstream molecules of EGFR, were also reduced in cell surface beta1,4GT1
      overexpressing cells. Furthermore, the translocations of Bad and Bax that are
      regulated by PKB/Akt and ERK1/2 were also increased in these cells. As a result,
      the release of cytochrome c from mitochondria to cytosol was increased and
      caspase-3 was activated. In contrast, RNAi-mediated knockdown of beta1,4GT1
      increased the autophosphorylation of EGFR. These results demonstrated that cell
      surface beta1,4GT1 may negatively regulate cell survival possibly through
      inhibiting and modulating EGFR signaling pathway.

PMID- 16786199
TI  - Modification of Gore suture passer instrument.
AB  - BACKGROUND: The Gore suture passer instrument is an ideal reusable device for
      various laparoscopic procedures albeit with a few drawbacks. The needle is not
      self-retracting inside the sheath and this leads to incomplete (manual)
      retraction of the needle, causing bending and breakage of the needle tip. The
      intracorporeal orientation of the suture grasper is difficult to maintain because
      the needle and suture grasper is fully rotational inside the handle. METHODS: We
      rectified these drawbacks by inserting a spring below the connecting nut in the
      handle component to make the needle self-retracting. The needle and suture
      grasper was stabilized by a screw in the main body of the handle to fit in a
      longitudinal slot cut on the brass connecting nut. RESULTS: Our modification made
      the needle and suture grasper self-retracting inside the sheath and stabilize the
      needle during the insertion. We have used this modified suture passer on 80
      patients without breakage and bending of the needle. CONCLUSION: This
      modification has made this device user friendly, steady, and has reduced the
      operation time.

PMID- 16786200
TI  - Bilateral renal artery aneurysm: percutaneous treatment with stent-graft
      placement.
AB  - A 51-year-old man with an 8-year history of hypertension (170/115 mmHg with two
      drugs) and altered renal function (5.6 mg/dl serum creatinine, 101 mg/dl BUN) was
      referred to our Department to evaluate the renal arteries and rule out
      renovascular hypertension. Doppler ultrasound and magnetic resonance angiography
      revealed significant bilateral renal artery stenosis and the presence of
      bilateral renal artery aneurysms. A self-expandable polytetrafluoroethylene
      (PTFE)-covered nitinol stent-graft was deployed in each renal artery to treat the
      stenoses and to exclude the aneurysm. Postprocedural digital subtraction
      angiography confirmed the resolution of the renal artery stenoses and the
      complete exclusion of the aneurysms. At the 6 month follow-up, color Doppler
      confirmed normal patency of the renal arteries with complete exclusion of the
      aneurysms and significant reduction of the blood pressure (130/85 mmHg with one
      drug) and serum creatinine levels (2.1 mg/dl).

PMID- 16786201
TI  - Removal of a trapped endoscopic catheter from the gallbladder via percutaneous
      transhepatic cholecystostomy: technical innovation.
AB  - BACKGROUND: Percutaneous cholecystostomy is used for a variety of clinical
      problems. METHODS: Percutaneous cholecystostomy was utilized in a novel setting
      to resolve a problematic endoscopic situation. OBSERVATIONS: Percutaneous
      cholecystostomy permitted successful removal of a broken and trapped endoscopic
      biliary catheter, in addition to helping treat cholecystitis. CONCLUSION: Another
      valuable use of percutaneous cholecystostomy is demonstrated, as well as
      emphasizing the importance of the interplay between endoscopists and
      interventional radiologists.

PMID- 16786202
TI  - Smokers: risks and complications in abdominal dermolipectomy.
AB  - Cigarette smoke has many detrimental effects on health, with consequences such as
      cardiovascular diseases, respiratory diseases, and tumors. In plastic surgery,
      these effects appear during the wound healing process. This retrospective study
      showed wound healing in 57 patients who had undergone abdominal dermolipectomy
      surgery. The patients were divided into two groups: smokers and nonsmokers.
      According to the results, smokers face a great complication risk for surgical
      wounds, which cause aesthetically more undesirable scars than observed in
      nonsmokers. The authors hypothesize that abstinence from smoking for 4 to 12
      weeks before surgery would improve the quality of the scars.

PMID- 16786203
TI  - Nipple reconstruction using the fleur-de-lis flap technique.
AB  - The authors propose a simple and reliable technique for nipple reconstruction
      characterized by minimal loss in vertical projection.

PMID- 16786204
TI  - Unilateral dichotomy of nipple (intraareolar polythelia) and areola: report of a
      case and surgical correction.
AB  - An unusual case of intraareolar polythelia with two nipples is presented. The
      dichotomy affected not only the nipple, but also the areola. No other breast
      malformation existed. Surgical correction was performed by transposition flaps
      sutured to one another in the center of the areola. The anatomic and functional
      results were satisfactory.

PMID- 16786205
TI  - Usefulness of the nipple-suspension piercing device after correction of inverted
      nipples.
AB  - The authors have devised a new piercing instrument for postoperative nipple
      suspension of inverted nipples. The instrument can be used not only
      postsurgically, but also for nipple suspension in light inverted nipple cases
      without surgical repair. Details of the device and the method of piercing are
      described.

PMID- 16786206
TI  - Correction of prominent ears with a new splinting technique.
AB  - Correction of prominent ears represents one of the main applications in plastic
      surgery. Apart from its cosmetic nature, this operation is important because of
      the psychological distress that the deformity causes patients. In this study, 40
      patients who underwent treatment for prominent ears in our department were
      evaluated. The classical surgical technique described by Chongchet followed by a
      new splinting procedure was performed. The advantages of this technique are
      described in comparison with traditional methods.

PMID- 16786208
TI  - Use of calcium channel blockers after stroke is not associated with poor outcome:
      a cohort from the registry of the Canadian stroke network.
AB  - BACKGROUND: Control of hypertension is essential for the secondary prevention of
      stroke. Although several trials have assessed the role of calcium channel
      blockers (CCBs) in the acute stroke, few address their safety and efficacy in
      secondary prevention. The recovery process after stroke requires neurite
      outgrowth, which may be dependent on activation of calcium channels and NMDA
      receptors. We asked whether treatment of hypertension using CCBs is safe during
      the recovery of patients following stroke and whether it contributes to their
      functional outcome. METHODS: The Registry of the Canadian Stroke Network provided
      access to information from 1545 patients with ischemic stroke. Primary outcome
      variables were mortality and functional outcome, which was assessed using the
      Stroke Impact Scale-16. RESULTS: Patients discharged on CCB had a 2.5% 6-month
      mortality rate compared with 5.5% in those who were not on CCB at discharge (OR
      0.38, 95% CI 0.17-0.88). There was no change in 6-month mortality with respect to
      treatment with ACE-I, B-blockers or diuretics at discharge. Patients that were
      admitted on CCB had improved SIS-16 at 6-months if they were also discharged on
      CCB, as compared with patients who had their CCB discontinued (73.8 veas 66.8, p
      = 0.032). CONCLUSIONS: CCB treatment at the time of discharge did not impede
      functional recovery, and was associated with reduced mortality and improved SIS
      16 at 6 months.

PMID- 16786209
TI  - Cortical damage in brains of patients with adult-form of myotonic dystrophy type
      1 and no or minimal MRI abnormalities.
AB  - OBJECTIVE: To evaluate, by using quantitative MRI metrics, subtle cortical
      changes in brains of patients with the adult form of myotonic dystrophy type I
      (DM1) who showed no or minimal abnormalities on MRI. BACKGROUND: DM1 is an
      autosomal dominant multisystem disorder caused by the expansion of CTG repeats in
      the myotonic dystrophy-protein kinase gene. Mild to severe involvement of the CNS
      can be part of the clinical features of the disease. Several MRI studies have
      demonstrated that both focal white matter (WM) lesions and diffuse grey matter
      atrophy can be found in the brains of DM1 patients. However, whether these two
      processes are related or may occur independently is not clear. DESIGN/METHODS:
      Ten genetically-proven DM1 patients who showed no or minimal abnormalities on MRI
      underwent a new brain MRI examination to obtain computerized measures of total
      and regional brain volumes normalized to head size and regional measurements of
      the magnetization transfer ratio (MTr). RESULTS: Normalized brain volumes (NBV)
      were significantly (p < 0.0001) lower in DM1 subjects than in a group of age- and
      sex-matched normal controls. Normalized cortical volumes (NCV) also were lower (p
      = 0.003) in DM1 subjects than in normal controls, whereas normalized WM volumes
      were not different between the two groups (p = 0.3). In agreement with this,
      values of MTr in the neocortex (cortical-MTr) were significantly (p = 0.006)
      lower in DM1 patients than in normal controls and this difference was not found
      in the WM tissue (p = 0.8). CONCLUSIONS: Neocortical damage seems to be evident
      in the absence of visible WM lesions suggesting that a neocortical pathology,
      unrelated to WM lesion formation, occurs in DM1 brains.

PMID- 16786210
TI  - Hemoglobin oxygen saturation as a marker of cerebral hemodynamics in carotid
      artery occlusion: an integrated transcranial doppler and near-infrared
      spectroscopy study.
AB  - Cerebral hemodynamics play a pivotal role in stroke pathogenesis. Transcranial
      Doppler (TCD) studies demonstrated the importance of cerebral vasomotor
      reactivity (VMR) on the outcome of carotid artery occlusion (CAO). So far,
      positron emission tomography represents the best technique for detecting both
      hemodynamic and metabolic aspects of cerebral perfusion adaptive processes in
      cerebrovascular patients. Near-infrared spectroscopy (NIRS) is a new method
      allowing for a non-invasive assessment of cerebral blood flow and hemoglobin (Hb)
      oxygenation parameters.A recent TCD and NIRS study demonstrated that patients
      with symptomatic CAO had lower VMR values measured by TCD and lower oxygen
      saturation (oxygen%) increases detected by NIRS than asymptomatic ones. The
      parameters were obtained simultaneously after CO(2) inhalation. The present study
      aims to investigate if Hb oxygen % could represent also at rest a marker of
      hemodynamic status in carotid disease.Thirty-five symptomatic and 17 asymptomatic
      patients with CAO underwent a simultaneous examination by means of TCD and NIRS
      at rest condition and during CO(2) reactivity test. Symptomatic patients
      presented with oxygen% values at rest higher (p = 0.001) and VMR values lower (p
      < 0.001) than asymptomatic subjects. According to a logistic model, for each
      unitary VMR increase, the odds of being symptomatic decreases of about 10% (OR =
      0.9, p = 0.001); for each unitary increase of oxygen% at baseline, this odd
      increases of about 23% (OR = 1.23, p = 0.031). In addition to TCD VMR values,
      oxygen hemoglobin saturation at rest detected by NIRS can discriminate
      symptomatic from asymptomatic patients with CAO. NIRS can add an important
      contribution to explain pathophysiological mechanisms of stroke occurrence.

PMID- 16786211
TI  - Frequency of current utilisation of complementary and alternative medicine by
      patients with multiple sclerosis.
AB  - OBJECTIVE: The purpose of the study was to examine the frequency and
      characteristics of complementary and alternative medicine (CAM) use among
      patients with multiple sclerosis (MS). METHOD: In order to collect
      sociodemographic and disease related variables as well as aspects of CAM
      utilisation 254 MS patients were examined with an interview. The investigation
      was completed by data of the neurological examination. RESULTS: At the time of
      investigation 67.3% of the MS patients reported that they were currently using
      one or more CAMs. Overall, most of the overall utilized therapies (90.6%) were
      chosen as a complement and 9.4% as an alternative therapy. Users of complementary
      medicine were more severely affected by the MS than non-users and had a longer
      duration of illness. No sociodemographic differences were found between users and
      non-users. When evaluating the efficacy of CAM, patients reported improvement in
      67.1%, no influence in 32.3% and worsening in 0.6% of the cases. 3.7% of the CAM
      therapies were accompanied by minor side effects. CONCLUSIONS: Since MS patients
      are frequently using CAM despite the absence of clinically proven efficacy and
      appraise it positively, further research on the motivation for utilisation and on
      objective effects of CAM are needed.

PMID- 16786213
TI  - Cardiac involvement in limb-girdle muscular dystrophy 2I : conventional cardiac
      diagnostic and cardiovascular magnetic resonance.
AB  - BACKGROUND: The C826A mutation in the fukutin-related protein (FKRP) gene is
      typically associated with autosomal recessive limb-girdle muscular dystrophy 2I
      (LGMD2I) but oligosymptomatic phenotypes and patients with predominant cardiac
      involvement are also described. OBJECTIVE: To assess cardiac involvement in
      patients with LGMD2I. PATIENTS: Nine patients from 5 families (2 female, 7 male)
      homozygous for the 826C > A FKRP mutation were included. METHODS: Additional to
      conventional cardiac investigations (electrocardiography and echocardiography)
      the patients underwent cardiovascular magnetic resonance imaging (CMR).
      RESULTS/CONCLUSION: Cardiac involvement was detected by CMR in eight of nine
      patients (reduced left ventricular ejection fraction in 6, enlargement of left
      ventricular end-diastolic volume in 2 and left ventricular mass in 2) and in four
      patients by conventional cardiac diagnostic investigations. Two of the nine
      patients showed no muscle weakness or atrophy but suffered myalgias; both had
      cardiac manifestation of the disease. CMR is a sensitive method for detecting
      cardiac abnormalities in patients with LGMD2I and can be used for early detection
      of mild or subclinical cardiac involvement.

PMID- 16786212
TI  - Interferon gamma quantification in cerebrospinal fluid compared with PCR for the
      diagnosis of tuberculous meningitis.
AB  - PURPOSE: To assess the utility of interferon gamma (INF-gamma) levels in
      cerebrospinal fluid (CSF), for the diagnosis of tuberculous meningitis (TBM), and
      compare these results with aPCR technique. METHODS: We studied CSF samples from
      patients with proven or probable TBM and a control group, composed by patients
      with other causes of meningitis and without meningitis. INFgamma levels were
      measured by radioimmunoassay. A PCR technique was performed using IS6110 primers.
      RESULTS: Of the 127 patients studied, 20 (15.6%) had TBM, 59 (46%) had meningitis
      of another aetiology and 49 (38.4%) had were HIV and non-HIV patients with normal
      CSF. The area below the ROC curve for interferon gamma levels in the diagnosis of
      TBM was 0.94. A cut-off of 6.4 IU/mL yielded a sensitivity of 70% and a
      specificity of 94%. False positive results were observed in 7 of the 59 patients
      (11.8%) with non-TB meningitis, (patients with herpetic meningoencephalitis and
      meningitis due to intracellular microorganisms). INF-gamma sensitivity was higher
      than PCR (70% vs. 65%). Both tests performed together showed higher sensitivity
      (80%) and specificity (92.6%). CONCLUSION: CSF INF-gamma levels (> 6.4 IU/mL) are
      very valuable in TBM diagnosis. PCR and INF-gamma could be simultaneously used to
      increase the diagnostic yield.

PMID- 16786215
TI  - Symptomatic epilepsy with a tumor in the nose.

PMID- 16786214
TI  - Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulation.
AB  - An open controlled trial of 0.75 mg/Kg/day prednisolone was conducted at a stage
      when the patients had started falling several times in a day and stopped on their
      attaining a chair bound stage, thus minimising the total period of steroid
      therapy. Out of the 67 DMD patients enrolled in this study, 44 were put on
      prednisolone therapy and 23 served as controls. All patients were followed-up at
      two-monthly intervals for two years and thereafter they continued to take their
      respective medications till their chair-bound stage; then the drug was gradually
      withdrawn. In the treatment group 24 patients could not continue the trial
      because of adverse effects - 14 due to excessive obesity, 3 due to measles, 4 due
      to pulmonary tuberculosis, 2 due to recurrent throat and chest infection and 1
      due to an unexplained high leukocyte count. Of the remaining 20 patients in the
      treatment group, steroid therapy was stopped in 5 patients as there was no
      improvement in power in six months. Fifteen patients in the treatment group and
      19 patients in the control group could be followed regularly for 2 years and then
      up to chair-bound stage. Outcome parameters included fall frequency, peak
      expiratory flow rate, limb muscle power, ability to lift weights, time taken in
      getting up from squatting position, walking 9 metres and climbing 13 stairs.
      Maximum improvement was noted between 2 and 4 months while mild improvement in
      some parameters continued up to six months. All parameters remained stabilised
      for 1 year or so, after which there was slight deterioration. Deterioration at 2
      years was, however, less than the natural course of events noted in control
      patients. Prednisolone treated patients and controls became chair bound at the
      mean age of 169 +/- 9 and 132 +/- 8 months respectively. Till the ideal stage of
      the disease and the type or dosage of starting steroid therapy is defined by
      specially designed studies, 0.75 mg/Kg/day prednisolone therapy may be started in
      DMD patients at the stage of frequent falls ( > 10 / day) on walking or increased
      get-up time ( > 10 s) as observed while testing Gowers' sign; this improves
      muscle power and timing of motor performance within 2-4 months of onset of
      therapy in about 75% of those who tolerate this therapy, with a possible gain of
      approximately 3 years in terms of independent walking.

PMID- 16786216
TI  - The neurological disorder associated with thyroid autoimmunity.
AB  - The neurological disorder associated with thyroid autoimmunity is an elusive
      disease that neurologists have learned to recognize in the last few years. The
      diagnosis is made, after excluding more common diseases, when neuropsychiatric
      symptoms develop in a patient with high serum concentrations of anti-thyroid
      antibodies. The clinical presentations of the disease and the many controversial
      issues surrounding the diagnosis, the pathogenesis, the role of thyroid
      autoantibodies, and the choice of therapy are reviewed and discussed in the light
      of the medical literature in English.

PMID- 16786217
TI  - Blink amplitude but not saccadic hypometria indicates carriers of Parkin
      mutations.
AB  - We investigated saccades, eyelid blinks, and their interaction in symptomatic (n
      = 22) and asymptomatic (n = 31) subjects with (n = 19) and without (n = 34)
      Parkin mutations. Saccadic hypometria was correlated with clinical symptoms of
      Parkinson's disease, irrespective of mutational status. By contrast, blink
      amplitude was increased in carriers of Parkin mutations independent of their
      clinical status. Saccade main sequence and blink effects on saccades were normal.
      We propose that increased blink amplitude may serve as an endophenotype in
      carriers of Parkin mutations.

PMID- 16786218
TI  - Comparison of a simple method for quantitation of intraepidermal nerve fibres
      with a standard image analysis method using hypothenar skin.
AB  - OBJECTIVES: To compare a simpler method for counting intraepidermal nerve fibres
      with a standard computer based image analysis method in normal subjects with skin
      taken from the hypothenar region. METHODS: In 40 healthy controls (mean age 41.1
      years, range 21-71, 24 Chinese, 11 Indian, 5 Malay, 30 females) intraepidermal
      nerve fibres per length of epidermis were determined using immunoperoxidase
      staining with the panaxonal antibody PGP 9.5. Under brightfield microscopy, two
      methods of determining the length of the epidermis were compared. A simpler
      method employing a microscope intraocular lens ruler was compared with the more
      complex gold standard using image software analysis . RESULTS: Intraepidermal
      nerve fibres per length of epidermis using the intraocular ruler method were 3.07
      nerve fibres/mm (2SD 1.56). The image software analysis obtained values of 3.05
      nerve fibres/mm (2SD 1.54). Correlation between the two tests was excellent
      (r=0.999 p= or <0.00001). Epidermal nerve fibre counts from hypothenar skin are
      lower than in more proximal sites. CONCLUSION: A simple method for counting
      intraepidermal nerve fibres produces results similar to those using standard
      software image analysis. This should help the implementation of this technique
      for wider use.

PMID- 16786219
TI  - On the ORigin of smell: odorant receptors in insects.
AB  - Olfaction, the sense of smell, depends on large, divergent families of odorant
      receptors that detect odour stimuli in the nose and transform them into patterns
      of neuronal activity that are recognised in the brain. The olfactory circuits in
      mammals and insects display striking similarities in their sensory physiology and
      neuroanatomy, which has suggested that odours are perceived by a conserved
      mechanism. Here I review recent revelations of significant structural and
      functional differences between the Drosophila and mammalian odorant receptor
      proteins and discuss the implications for our understanding of the evolutionary
      and molecular biology of the insect odorant receptors.

PMID- 16786220
TI  - Class III adenylyl cyclases: molecular mechanisms of catalysis and regulation.
AB  - Class III adenylyl cyclases are the most abundant type of cyclic AMP-producing
      enzymes. The adjustment of the cellular levels of this second messenger is
      achieved by a variety of regulatory mechanisms which couple signals to adenylyl
      cyclase activity. Because of the divergent nature of stimuli which impinge on
      these enzymes, highly individualized class III adenylyl cyclases have evolved in
      metazoans, eukaryotic unicells and bacteria. Regulation usually exploits the
      dimeric structure of the catalyst, whose active centres form at the dimer
      interface. The fold of the catalytic domains and the basic catalytic mechanisms
      are similar in all class III adenylyl cyclases, and substrate binding generally
      closes the active site by an induced-fit mechanism. Regulatory inputs can result
      in dramatic rearrangements of the catalytic domains within the dimer, which often
      are based on rotational movements.

PMID- 16786221
TI  - nDsbD: a redox interaction hub in the Escherichia coli periplasm.
AB  - DsbD is a redox-active protein of the inner Escherichia coli membrane possessing
      an N-terminal (nDsbD) and a C-terminal (cDsbD) periplasmic domain. nDsbD
      interacts with four different redox proteins involved in the periplasmic
      disulfide isomerization and in the cytochrome c maturation systems. We review
      here the studies that led to the structural characterization of all soluble DsbD
      domains involved and, most importantly, of trapped disulfide intermediate
      complexes of nDsbD with three of its four redox partners. These results revealed
      the structural features enabling nDsbD, a 'redox hub' with an immunoglobulin-like
      fold, to interact efficiently with its different thioredoxin-like partners.

PMID- 16786222
TI  - Insulin/IGF signalling in neurogenesis.

PMID- 16786223
TI  - Coaxing bone marrow stromal mesenchymal stem cells towards neuronal
      differentiation: progress and uncertainties.
AB  - Multipotent adult stem cells capable of developing into particular neuronal cell
      types have great potential for autologous cell replacement therapy for central
      nervous system neurodegenerative disorders and traumatic injury. Bone marrow
      derived stromal mesenchymal stem cells (BMSCs) appear to be attractive starting
      materials. One question is whether BMSCs could be coaxed to differentiate in
      vitro along neuronal or glial lineages that would aid their functional
      integration post-transplantation, while reducing the risk of malignant
      transformation. Recent works suggest that BMSCs could indeed be differentiated in
      vitro to exhibit some cellular and physiological characteristics of neural cell
      lineages, but it is not likely to be achievable with simple chemical treatments.
      We discussed recent findings pertaining to efforts in neuronal differentiation of
      BMSCs in vitro, and results obtained when these were transplanted in vivo.

PMID- 16786224
TI  - Soluble proteins in insect chemical communication.
AB  - Our understanding of the biochemical mechanisms that mediate chemoreception in
      insects has been greatly improved after the discovery of olfactory and taste
      receptor proteins. However, the presence of soluble polypeptides in high
      concentration around the dendrites of sensory neurons still poses unanswered
      questions. More than 2 decades after their discovery and despite the wealth of
      structural information available, the physiological function of odorant-binding
      proteins is not well understood. More recently, members of a second family of
      soluble polypeptides, the chemosensory proteins, were also discovered in the
      lymph of chemosensilla. Here we review the structural properties of both classes
      of soluble proteins, their affinity to small ligands, and their expression in the
      different parts of the insect body and subcellular localisation. Finally, we
      discuss current ideas and models of the role of such proteins in insect
      chemoreception.

PMID- 16786225
TI  - Thiamine pyrophosphate: an essential cofactor for the alpha-oxidation in mammals-
      implications for thiamine deficiencies?
AB  - The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine
      pyrophosphate (TPP)-dependent peroxisomal enzyme involved in the alpha-oxidation
      of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a
      role of TPP in these processes. Until then, TPP had not been implicated in
      mammalian peroxisomal metabolism. The effect of thiamine deficiency on 2-HPCL and
      alpha-oxidation has not been studied, nor have possible adverse effects of
      deficient alpha-oxidation been considered in the pathogenesis of diseases
      associated with thiamine shortage, such as thiamine-responsive megaloblastic
      anemia (TRMA). Experiments with cultured cells and animal models showed that
      alpha-oxidation is controlled by the thiamine status of the cell/tissue/organism,
      and suggested that some pathological consequences of thiamine starvation could be
      related to impaired alpha-oxidation. Whereas accumulation of phytanic acid and/or
      2-hydroxyfatty acids or their alpha-oxidation intermediates in TRMA patients
      given a normal supply of thiamine is unlikely, this may not be true when
      malnourished.

PMID- 16786226
TI  - Rubinstein-Taybi syndrome: molecular findings and therapeutic approaches to
      improve cognitive dysfunction.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare human genetic disorder characterized by
      mental retardation and physical abnormalities. Many RTS patients have a genetic
      mutation which has been mapped to chromosome 16p13.3, a genomic region encoding
      cyclic AMP (cAMP) response element binding protein (CREB) binding protein (CBP).
      CBP is a transcriptional co-activator that binds to CREB when the latter is
      phosphorylated and promotes gene transcription. CREB-dependent gene transcription
      has been shown to underlie long-term memory formation. In this review we will
      focus on recent findings regarding the biology of CBP and its role in memory
      formation and cognitive dysfunction in RTS. We will also review the role of CBP
      in other neurological disorders, including Alzheimer's disease, Huntington's
      disease and amyotrophic lateral sclerosis. Finally, we will discuss novel
      therapeutic approaches targeted to CBP/CREB function for treating the cognitive
      dysfunction of RTS and other neurological disorders.

PMID- 16786227
TI  - Arterial wall cholesterol content is a predictor of development and severity of
      arterial thrombosis.
AB  - BACKGROUND: It is unclear if total cholesterol content contributes to the
      severity of cardiovascular events by affecting the amount of thrombosis. This
      study evaluated relationships between cholesterol levels and the amount of
      thrombosis in an atherosclerotic rabbit model of plaque disruption and
      thrombosis. METHODS: Three groups of NZW rabbits were used: normal rabbits (Group
      I, n = 4); atherosclerotic rabbits (Group II, n = 4); and atherosclerotic rabbits
      with pharmacologically triggered thrombosis (Group III, n = 16). Atherosclerosis
      was induced by feeding a cholesterol enriched diet and balloon
      deendothelialization. At post-mortem, platelet-rich thrombus and arterial wall
      cholesterol were quantified and histology performed by light and electron
      microscopy. RESULTS: Arterial wall cholesterol was strongly correlated to serum
      cholesterol in all groups (r = 0.94, p < 0.0001). There was a significant
      correlation between the thrombus surface area with arterial wall cholesterol in
      Group III (r = 0.71, p < 0.002). Serum cholesterol, arterial wall cholesterol,
      and thrombus surface area were all significantly correlated but only arterial
      wall cholesterol was an independent predictor of thrombosis. A threshold specific
      for this model was noted for serum and arterial cholesterol levels above which
      thrombosis consistently occurred. CONCLUSIONS: Arterial wall cholesterol was
      strongly correlated to serum cholesterol and thrombosis severity. Serum
      cholesterol, arterial wall cholesterol and thrombus surface area were all
      integrally related.A model of plaque disruption and thrombosis was used to
      demonstrate a correlation between serum and arterial wall cholesterol (r = 0.94;
      p < 0.0001); arterial wall cholesterol and the amount of thrombosis (surface
      area; r = 0.71, p < 0.002). A threshold of serum and arterial cholesterol was
      determined at which thrombosis occurred in this model.

PMID- 16786228
TI  - Dose escalation trial of the efficacy, safety, and pharmacokinetics of a novel
      fibrinolytic agent, BB-10153, in patients with ST elevation MI: results of the
      TIMI 31 trial.
AB  - BACKGROUND: Currently available fibrinolytic agents are limited by their ability
      to restore normal blood flow in only half of patients, the risk of reocclusion,
      and the risk of intracranial hemorrhage. The genetically engineered agent BB
      10153 is activated by thrombin, not plasminogen activator enzymes, which limits
      its activity to the site of thrombus which may in turn reduce the risk of
      systemic bleeding. BB-10153 also has a relatively long half-life of 3-4 hours,
      which may also limit the potential for early reocclusion [1, 2]. METHODS: The
      study was a phase II, open-label, multi-center, dose escalation, single-dose
      administration study to determine the efficacy, safety, tolerability,
      pharmacokinetics and pharmacodynamics of BB-10153 in ST segment elevation MI
      (STEMI). STEMI patients (n = 50) received a single dose of BB-10153 at one of six
      dose levels (1.0, 2.0, 3.0, 5.0, 7.5 and 10 mg/kg). The primary endpoint was TIMI
      flow grade (TFG) 3 at 60 minutes following the intravenous bolus of BB-10153.
      RESULTS: Mean area under the curve for drug concentration ranged from 48.0
      microg.h/mL in the 1 mg/kg dose group to 788.6 microg.h/mL in the 10 mg/kg dose
      group. Likewise, mean Cmax generally increased with dose over the entire dose
      range, from 4.9 microg/mL in the 1 mg/kg dose group to 139.6 microg/mL in the 10
      mg/kg dose group. The mean apparent terminal half-life (t1/2) was 4.4 hours
      (range 2.2 to 7.6 hours). Few patients in the 1-3 mg/kg dosage groups achieved
      TFG 3 on the one-hour post-dose angiogram (4/20, 20%), and no patients achieved
      complete ST segment resolution. The 5, 7.5 and 10 mg/kg doses were associated
      with similar rates of TIMI grade 3 flow of approximately three per seven
      patients. Pooling TFG 3 data from the 5, 7.5 and 10 mg/kg groups yielded a TIMI
      grade 3 flow rate of 34% (n = 10/29; range 29-43%). No patients experienced 30
      day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during
      the study. One patient experienced recurrent angina and developed recurrent
      myocardial ischemia requiring urgent revascularization. Three patients sustained
      TIMI major bleeding events (one in 1 mg/kg group, two in 7.5 mg/kg group), six
      patients sustained TIMI minor bleeds (one in the 2, 3, 7.5 and 10 mg/kg groups,
      two in the 5 mg/kg group), twp patients sustained TIMI minimal bleeds (one in
      each of the 2 and 10 mg/kg groups) and no patients sustained intracranial
      hemorrhage (ICH). CONCLUSION: In a dose escalation study of a single intravenous
      bolus, the novel fibrinolytic agent, BB-10153 was associated with a rise in the
      mean area under the curve and Cmax for drug concentration over the dose range 1
      to 10 mg/kg. Higher doses were associated with a range of TIMI grade 3 flow of 29
      43%, and no patients experienced 30-day death, recurrent acute MI, cardiogenic
      shock, stroke or anaphylaxis during the study. In a dose escalation study of a
      single intravenous bolus, the novel fibrinolytic agent, BB-10153 was associated
      with a rise in the mean area under the curve and Cmax for drug concentration over
      the dose range 1 to 10 mg/kg. Higher doses were associated with a range of TIMI
      grade 3 flow of 29-43%, and no patients experienced 30-day death, recurrent acute
      MI, cardiogenic shock, stroke or anaphylaxis during the study.

PMID- 16786229
TI  - Pharmacy-managed anticoagulation: assessment of in-hospital efficacy and
      evaluation of financial impact and community acceptance.
AB  - BACKGROUND: The dangers of thrombosis are well known and yet current therapy
      presents a paradox; effective methods of pharmacological anticoagulation are
      available, but underemployed. The risks associated with the use of
      anticoagulants, especially warfarin, and the requirement of meticulous dosing
      with subsequent vigilant monitoring provides some explanation for this
      discrepancy. Efforts have been made to address this incongruity and increase
      anticoagulation treatment while mitigating complications; these include the
      development of dosing nomograms, patient self-monitoring of anticoagulation
      status, and increased pharmacist participation in anticoagulation management.
      Although the latter option has proven effective in outpatient clinics, its in
      hospital application has received less attention. Therefore, our primary goal was
      to review the published literature to evaluate the efficacy of in-hospital,
      pharmacy-managed anticoagulation. In addition, our secondary goals were to assess
      the potential financial benefit and community acceptance of such pharmacist
      management. METHODS: Potentially relevant studies were identified by searching
      PubMed; however, because some pharmacy journals are not included in this
      database, we also used internet search engines to locate articles. We
      subsequently employed the Science Citation Index to find additional papers that
      had referenced articles identified by our initial searches. RESULTS: Several
      pilot studies, focusing primarily on adherence to warfarin dosing guidelines,
      found general equivalence between pharmacist and physician management and
      specifically illustrated the potential benefit gained simply through adherence to
      protocols. Nevertheless, these studies frequently lacked appropriate statistical
      analysis and examined small, and often heterogeneous, patient groups. Larger
      comparative studies also possessed some of the same flaws; however, taken
      together the equivalence and, in some cases improvement, in patient outcomes
      (e.g., greater control of International Normalized Ratios and decreased length of
      hospital stay) that they demonstrated suggest the value of increased pharmacist
      participation in anticoagulation therapy. Studies using heparin-based
      anticoagulation reported similar positive findings and hence support the warfarin
      results. Both published studies examining financial implications of in-hospital
      pharmacy management indicated potential for considerable savings. Finally,
      although we identified no in-hospital studies of community acceptance, positive
      survey results indicted that the majority of physicians and patients accepted
      pharmacy-managed outpatient anticoagulation. CONCLUSIONS: The reported outcomes
      of pharmacy-managed in-hospital anticoagulation therapy appear at least equal,
      and sometimes superior, to those obtained through standard care; however, the
      lack of large well-designed trials prevents drawing definitive conclusions.
      Nevertheless, the continued and likely increased future need for anticoagulation
      in general and warfarin therapy in particular suggests that increased pharmacist
      involvement could enhance the quality of patient care.

PMID- 16786230
TI  - Extended-duration thromboprophylaxis in acutely ill medical patients with recent
      reduced mobility: methodology for the EXCLAIM study.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a significant cause of mortality and
      morbidity in medical patients. Although thromboprophylaxis with enoxaparin
      reduces the risk of VTE in these patients, the optimal duration of therapy is not
      currently known. The EXCLAIM (EXtended CLinical prophylaxis in Acutely Ill
      Medical patients) study is designed to compare the efficacy and safety of
      extended-duration thromboprophylaxis using enoxaparin with the standard regimen
      of enoxaparin in acutely ill medical patients with recent reduced mobility.
      METHODS: All enrolled acutely ill medical patients receive enoxaparin 40 mg
      subcutaneously once daily for 10 +/- 4 days. Eligible patients are then
      randomized in a blinded manner to receive either extended-duration
      thromboprophylaxis with enoxaparin 40 mg subcutaneously once daily or placebo
      subcutaneously once daily for an additional 28 +/- 4 days. The primary efficacy
      endpoint is the incidence of VTE during the 28 +/- 4 days after randomization.
      This study utilizes a standardized bilateral compression ultrasonography
      examination protocol that consists of an intensive interrogation of the deep
      veins of the lower extremities for proximal deep-vein thrombosis. The secondary
      efficacy endpoints are the rate of symptomatic VTE during the 3 months after
      randomization and mortality at 3 and 6 months after enrollment. The primary
      safety endpoint is the incidence of major hemorrhagic complications during the 28
      +/- 4 days after randomization. RESULTS: To date, 3,983 patients, with a broad
      range of medical conditions, have been included in the study. Almost one third of
      the enrolled patients with reduced mobility are acutely ill due to respiratory
      insufficiency and one third have infectious diseases. CONCLUSIONS: The EXCLAIM
      study is designed to show the efficacy and safety of extended-duration
      thromboprophylaxis using enoxaparin in acutely ill medical patients with recent
      reduced mobility, which may potentially lead to a reduction in the incidence of
      late VTE events in these patients. The EXCLAIM (EXtended CLinical prophylaxis in
      Acutely Ill Medical patients) study, involving 4,726 acutely ill medical patients
      with recent reduced mobility, is designed to compare the efficacy and safety of
      extended-duration thromboprophylaxis using 40 mg once daily enoxaparin (38 +/- 4
      days) with the standard regimen for enoxaparin (40 mg once daily for 10 +/- 4
      days). The objective of this study is to demonstrate that the extended-duration
      enoxaparin regimen is an effective and safe thromboprophylaxis regimen out of
      hospital.

PMID- 16786231
TI  - Transport for abciximab facilitated primary angioplasty versus on-site
      thrombolysis with a liberal rescue policy: the randomised Holland Infarction
      Study (HIS).
AB  - AIMS: As of to date, the only large transportation trial comparing on-site fibrin
      specific thrombolysis with transfer for primary angioplasty in patients
      presenting in a referral centre is the DANAMI-2 trial, with only 3% rescue
      angioplasty. The Holland Infarction Study (HIS) compared abciximab facilitated
      primary angioplasty (FP) with on-site fibrin-specific thrombolytic therapy (TT)
      with a liberal protocol-driven rescue angioplasty (transport to intervention
      centre in case < 50% ST resolution at 60 min). METHODS AND RESULTS: Patients in a
      referral centre without shock and < 4.5 h of chest pain presenting with ST
      elevation having > or = 12 mm ST-segment shift were randomised to either
      strategy. Of the originally planned 900 patients only 48 were included due to
      suspension of financial funding. Death, recurrent MI and stroke at one year was
      8% for the FP-group and 22% for the TT-group (p = 0.2). Two hours after
      randomisation the rates of complete ST-segment resolution (> or =70%) were 52%
      and 35%, respectively (p = 0.2). CONCLUSION: This prematurely discontinued
      randomised transportation trial shows favorable trends with respect to long-term
      clinical outcome and early ST-resolution for abciximab facilitated primary
      angioplasty. In view of the real world delays associated with interhospital
      transport for primary angioplasty, treatment strategies focusing on early fibrin
      specific lysis with a liberal selective rescue policy are warranted.

PMID- 16786233
TI  - The mean platelet volume in gestational diabetes.
AB  - OBJECTIVE: To compare the platelet count and mean platelet volume (MPV) values of
      pregnancies diagnosed with gestational diabetes with those of healthy
      pregnancies. MATERIAL-METHOD: Between June 2003 and September 2004, 100 healthy
      pregnancies and 100 pregnancies with gestational diabetes were studied at Gazi
      University, Department of Obstetrics and Gynecology. RESULTS: While no
      statistically significant difference was observed in the platelet count between
      the two groups, the MPV of the gestational diabetes group (9.4 +/- 1.6 fl) was
      evaluated to be significantly higher than the MPV of the healthy pregnancy group
      (8.3 +/- 1.1 fl). Additionally, when linear regression analysis was performed an
      inverse relationship was observed between platelet number and MPV. CONCLUSION:
      There is a need for further research focusing on the platelet function in the
      observation and treatment of gestational diabetes, which can pose the risk of
      developing Type 2 diabetes for the mother and has negative consequences for the
      fetus.

PMID- 16786232
TI  - Intracoronary bolus administration of eptifibatide during percutaneous coronary
      stenting for non ST elevation myocardial infarction and unstable angina.
AB  - BACKGROUND: Distal embolization of thrombotic debris may occur during and after
      percutaneous coronary intervention (PCI) for acute coronary syndromes. This may
      lead to impaired microvascular perfusion, myocardial infarction and increased
      morbidity and mortality. In vitro studies suggest that high local concentrations
      of a glycoprotein IIb/IIIa inhibitor may be effective in disaggregating thrombus
      and thereby prevent microvascular compromise. We hypothesized that intracoronary
      (IC) administration of eptifibatide during stent implantation for unstable
      angina/non ST elevation myocardial infarction (UA/NSTEMI) would be safe and would
      lead to an acceptable rate of normal myocardial perfusion. METHODS: In 54
      patients with UA/NSTEMI, 2 boluses of 180 mcg/kg of eptifibatide each were
      administered via the IC route during PCI. Data were retrospectively collected and
      reviewed by an independent core laboratory. RESULTS: No adverse events including
      arrhythmias occurred during IC administration of eptifibatide. There were no
      deaths or urgent revascularizations among patients treated with IC eptifibatide.
      One patient (2.0%) sustained a post-procedure myocardial infarction. One patient
      sustained a TIMI major bleeding event due to a gastrointestinal bleed. There were
      no TIMI minor bleeding events. Normal post PCI TIMI Myocardial Perfusion Grade
      was observed in 54% of patients. CONCLUSION: IC bolus administration of
      eptifibatide was feasible and safe among patients with UA/NSTEMI. Larger
      prospective and randomized studies are warranted to further explore the efficacy
      of this strategy. Intracoronary eptifibatide administration during PCI for
      UA/NSTEMI is feasible and safe.

PMID- 16786234
TI  - Host-guest composites for induced hemostasis and therapeutic healing in traumatic
      injuries.
AB  - INTRODUCTION: The United States military currently outfits our soldiers with a
      zeolite-based hemostatic agent (HA) that is applied directly onto a traumatic
      wound to induce hemostasis and prevent loss of life from exsanguination. The
      goals of this work were to identify and implement strategies to attenuate a
      tissue burning side effect associated with the HA, resulting from a large release
      of heat upon hydration, without adversely affecting the wound healing properties.
      Five ion exchanged derivatives of the parent HA were prepared and characterized
      with regard to their material and thermal properties, in vitro hemostatic
      efficacy, and antibacterial activity. METHODS: The five host-guest high-surface
      area HAs were prepared by ion exchanging the zeolite linde type 5A with aqueous
      salt solutions under controlled conditions. The modified HAs were characterized
      by TGA, DSC, Thermal Imaging, SEM, XRD, XPS, BET, and a Thromboelastograph (TEG)
      was employed to assay the in vitro hemostatic efficacy. Antibacterial activity
      was assayed by measuring the zone of no growth of Pseudomonas aeruginosa biofilms
      growing in contact with the ion exchanged HAs. RESULTS: The heat released during
      application of the HA can be minimized from 680 J/g to 420 J/g by ion exchanging
      the calcium ions in zeolite linde type 5A with cations of a reduced hydration
      enthalpy. Zeolite-based HAs that demonstrate in vitro clot induction time of R <
      or = 1.8 min, and with surfaces areas > or = 634 m2/g, correlate with 75% in vivo
      swine survivability of a universally lethal groin injury. Silver exchanged HA
      maintained a zone of no growth of P. aeruginosa with a surface area twice the
      geometrical surface area of an HA pressed pellet for 24 hours in an LB Agar
      assay. CONCLUSIONS: Two strategies for reducing the large amount of heat released
      by a zeolite-based HA during application have been described and quantified: (1)
      ion exchange and (2) prehydration. Five ion-exchanged derivatives of the original
      HA have been prepared and assayed for hemostatic efficacy both in vitro, by TEG,
      and in vivo, by clinical swine trials. Contact activation coagulation rates,
      alpha, were found to increase with the amount of heat released by the HA. In
      Vitro clot induction time, R, and HA surface area have been identified as
      predictors of in vivo hemostatic performance. A proposed rationale for selecting
      hemostatic materials based on these parameters will likely reduce the quantity of
      experiments involving animals, and the associated labor and capital costs,
      necessary to test a new HA. A method for incorporating antibacterial activity
      against gram negative P. aeruginosa into the Ag-exchanged formulation of zeolite
      LTA-5A has been described and substantiated.

PMID- 16786235
TI  - Treatment dosage recommendation for fondaparinux in a patient with heparin
      induced thrombocytopenia.

PMID- 16786236
TI  - Cholesterol, C-reactive protein, and cerebrovascular events following intensive
      and moderate statin therapy.
AB  - BACKGROUND: While statins have been shown to reduce cerebrovascular events (CVE),
      the relationship between cholesterol, C-reactive protein (CRP), and CVE in
      patients treated with different statin strategies is still being explored.
      METHODS: PROVE IT-TIMI 22 was a randomized trial of intensive (atorvastatin 80
      mg/day) and moderate (pravastatin 40 mg/day) statin therapy in 4,162 patients
      with acute coronary syndromes followed for an average of 24 months; serial
      biomarkers allowed for an assessment of the lipid and non-lipid effects of
      statins as they relate to CVE. RESULTS: In this study, 45 patients on intensive
      statin therapy and 40 patients on moderate statin therapy had a CVE during the
      study period (2.1% v. 1.9%, P = 0.62). While the lipid profiles of patients with
      and without CVE were similar, those with CVE had higher CRP levels at 30 days and
      4 months (2.7 v. 1.9, 2.4 v. 1.7 mg/L; P = 0.012, P = 0.005). Day 30 CRP remained
      an independent predictor of CVE after adjusting for age, development of atrial
      fibrillation, diabetes, and prior CVE. Patients with low density lipoprotein
      (LDL) levels < 70 mg/dL and > or = 70 mg/dL had similar rates of CVE, while
      patients with CRP < 2 mg/L tended to have lower event rates when compared to
      those with higher levels. The lowest rates of CVE were seen in patients who had
      LDL < 70 mg/dL and CRP < 2 mg/L. CONCLUSION: In PROVE IT--TIMI 22, achieved LDL
      levels did not appear to independently impact the rate of CVE. In contrast,
      patients with elevated CRP levels were at higher risk of stroke or transient
      ischemic attack, reinforcing the link between inflammation and CVE. The goal of
      this PROVE IT-TIMI 22 sub-study was to examine the relationship between
      cholesterol, CRP, and CVE in patients on intensive and moderate statin therapy.
      The achieved lipid levels were similar in patients with and without a CVE;
      however, the achieved levels of CRP were higher in patients who subsequently
      developed a stroke or TIA. These findings further support the relationship
      between inflammation and CVE.

PMID- 16786237
TI  - Differential diagnosis and management of acute profound thrombocytopenia by
      tirofiban: a case report.
AB  - Although the glycoprotein IIb/IIIa receptor inhibitors have improved outcomes of
      patients with acute coronary syndrome (ACS), therapy with these agents may cause
      thrombocytopenia with bleeding complications. This adverse effect is seemed to be
      rare with tirofiban. In this report, we describe a case of acute profound
      thrombocytopenia within two hours of tirofiban administration and review the
      differential diagnosis and the management of thrombocytopenia.

PMID- 16786238
TI  - Multiple coronary thrombosis and stent implantation to the subtotally occluded
      right renal artery in a patient with essential thrombocytosis: a case report with
      review.
AB  - Essential thrombocytosis is a myeloproliferative disorder of unknown etiology
      manifested clinically by the overproduction of platelets in the absence of a
      definable cause. Platelet dysfunction in essential thrombocytosis results in both
      hemorrhage and thrombosis. It is one of the rare causes of ischemic
      cardiovascular events. Fewer than 20 cases of essential thrombocytosis with
      involvement of coronary arteries leading to acute coronary syndromes or
      myocardial infarction have been reported. We report a case of multiple coronary
      thrombosis involving the left anterior descending artery and circumflex artery
      and stent implantation to the subtotally stenotic right renal artery in a women
      with unstable angina pectoris, essential thrombocytosis and previous history of
      renal artery trombosis.

PMID- 16786240
TI  - New tools for G-protein coupled receptor (GPCR) drug discovery: combination of
      baculoviral expression system and solid state NMR.
AB  - Biotechnology using molecular biology, biochemistry, biophysics, and
      computational approaches provides an alternative approach for classical
      pharmacological screening to look at ligand-receptor interactions and receptor
      specificity, which should support the design of selective drugs based on detailed
      structural principles. This review addresses specific approaches to study
      function, structure and relevance of a major pharmaceutical target, namely the G
      Protein Coupled Receptors (GPCRs). The main aim of this review has been to
      exploit and combine GPCR over-expression in a baculoviral expression system with
      solid-state MAS NMR (ssNMR) approaches for the elucidation of electronic
      structures of the coordinating ligands/drugs and their modes of interactions with
      the GPCRs. This review summarizes the approaches, possible future experiments and
      developments using the above combination of tools for GPCR drug discovery.

PMID- 16786239
TI  - Preoteomics, metabolomics and progenitor cells in acute coronary syndromes.

PMID- 16786241
TI  - Reduction of trienoic fatty acid content by expression of a double-stranded RNA
      of a plastid omega-3 fatty acid desaturase gene in transgenic tobacco.
AB  - Plastid omega-3 fatty acid desaturase catalyzes the conversion of dienoic fatty
      acids (16:2 and 18:2) to trienoic fatty acids (16:3 and alpha-18:3) in
      glycerolipids which are the main constituents of chloroplast membranes. We
      produced transgenic tobacco plants that express the transcript of a double
      stranded RNA (dsRNA) of tobacco plastid omega-3 fatty acid desaturase gene,
      NtFAD7. In these transgenic plants, 16:3 and alpha-18:3 content in leaves
      decreased to less than 2.7% and 7.5-10.4%, respectively, when compared with the
      control plant. The steady-state NtFAD7 mRNA was not detected in the transgenic
      plants. These results indicate that down-regulation of the transcript level in
      the NtFAD7 by introduction of NtFAD7 dsRNA constructs is useful to decrease the
      trienoic fatty acid contents of the vegetative tissues in higher plants.

PMID- 16786242
TI  - Regulation of two photosynthetic pigment-related genes during stress-induced
      pigment formation in the green alga, Dunaliella salina.
AB  - The expression of mRNAs coding for 1-deoxyxylulose-5-phosphate synthase (DXS) and
      phytoene synthase (PSY) were studied in Dunaliella salina grown under nitrogen
      sufficient (NS) and nitrogen-limited (NL) conditions. Under NS conditions growth
      was 2.5 times higher than under NL conditions. No differences were found in
      chlorophyll a content per cell, and total carotenoid content per cell was 5.33 pg
      1(-1) for the NS treatment and 7.76 pg 1(-1) for the NL. DXS transcripts
      exhibited diminished expression under NL conditions, peaking at day 15 of
      cultivation in both treatments. Simultaneously, PSY transcripts exhibited
      constant expression under both conditions. These results suggest that these genes
      play an important role in the balance of photosynthetic pigments during pigment
      accumulation.

PMID- 16786243
TI  - Production of high-content galacto-oligosaccharide by enzyme catalysis and
      fermentation with Kluyveromyces marxianus.
AB  - Of three beta-galactosidases from Aspergillus oryzae, Kluyveromyces lactis and
      Bacillus sp., used for the production of low-content galacto- oligosaccharides
      (GOS) from lactose, the latter produced the highest yield of trisaccharides and
      tetrasaccharides. GOS production was enhanced by mixing beta-galactosidase
      glucose oxidase. The low-content GOS syrups, produced either by beta
      galactosidase alone or by the mixed enzyme system, were subjected to the
      fermentation by Kluyveromyces marxianus, whereby glucose, galactose, lactose and
      other disaccharides were depleted, resulting in up to 97% and 98% on a dry weight
      basis of high-content GOS with the yields of 31% and 32%, respectively.

PMID- 16786244
TI  - New solid-state fermentation chamber for bulk production of aerial conidia of
      fungal biocontrol agents on rice.
AB  - A novel solid-state fermentation apparatus, namely an upright multi-tray
      conidiation chamber, was developed to facilitate the production of aerial conidia
      of fungal biocontrol agents, such as Beauveria bassiana. The chamber with 25
      bottom-meshed metal trays had a capacity of > or =50 kg rice with each tray
      holding > or =2 kg. In repeated trials, a mean yield of 2.4 (1.8-2.7) x 10(12)
      conidia kg(-1) rice was harvested from the 7-day cultures of B. bassiana in a
      fully loaded chamber. The new apparatus has a high potential for bulk production
      of fungal conidia.

PMID- 16786245
TI  - Enantioselective Baeyer-Villiger oxidation of bicyclo[3.2.0]hept-2-en-6-One with
      fungi: optimization of biotransformation and use of TiO2 as support of cell
      growth.
AB  - Fungi from Amazonian forest soil (Ecuador) and an Italian factory were screened
      for Baeyer-Villiger (BV) oxidation of bicyclo [3.2.0]hept-2-en-6-one to 2
      oxabicyclo[3.3.0]oct-6-en-3-one (Corey's lactone). Isolates of Fusarium sp. and
      F. solani produced the (+)-(1R,5S)-lactone while isolates of Aspergillus
      terricola and A. amazonicus afforded the (-)-(1S,5R)-lactone. Highest conversions
      (85% yield and 70% enantiomeric excess) were obtained with A. amazonicus grown in
      presence of 2.7 mM titanium dioxide.

PMID- 16786246
TI  - Lactic acid production from sugar-cane juice by a newly isolated Lactobacillus
      sp.
AB  - A newly isolated sucrose-tolerant, lactic acid bacterium, Lactobacillus sp.
      strain FCP2, was grown on sugar-cane juice (125 g sucrose l(-1), 8 g glucose l(
      1) and 6 g fructose l(-1)) for 5 days and produced 104 g lactic acid l(-1) with
      90% yield. A higher yield (96%) and productivity (2.8 g l(-1 )h(-1)) were
      obtained when strain FCP2 was cultured on 3% w/v (25 g sucrose l(-1), 2 g glucose
      l(-1) and 1 g fructose l(-1)) sugar-cane juice for 10 h. Various cheap nitrogen
      sources such as silk worm larvae, beer yeast autolysate and shrimp wastes were
      also used as a substitute to yeast extract.

PMID- 16786247
TI  - Gene transfer by DNA/mannosylated chitosan complexes into mouse peritoneal
      macrophages.
AB  - Chitosan is a biodegradable and biocompatible polymer and is useful as a non
      viral vector for gene delivery. In order to deliver pDNA/chitosan complex into
      macrophages expressing a mannose receptor, mannose-modified chitosan (man
      chitosan) was employed. The cellular uptake of pDNA/man-chitosan complexes
      through mannose recognition was then observed. The pDNA/man-chitosan complexes
      showed no significant cytotoxicity in mouse peritoneal macrophages, while
      pDNA/man-PEI complexes showed strong cytotoxicity. The pDNA/man-chitosan
      complexes showed much higher transfection efficiency than pDNA/chitosan complexes
      in mouse peritoneal macrophages. Observation with a confocal laser microscope
      suggested differences in the cellular uptake mechanism between pDNA/chitosan
      complexes and pDNA/man-chitosan complexes. Mannose receptor-mediated gene
      transfer thus enhances the transfection efficiency of pDNA/chitosan complexes.

PMID- 16786248
TI  - Real-time fluorogenic PCR assays for the detection of entA, the gene encoding
      staphylococcal enterotoxin A.
AB  - Staphylococcal enterotoxin A (SEA) is among the most potent of the growing list
      of known enterotoxins produced by Staphylococcus aureus. SEA, a 27 kDa monomeric
      protein, is encoded by the entA gene. We have developed two real-time fluorogenic
      PCR assays for the detection of nucleic acid sequences in entA. The assays are
      useful in detecting and identifying strains of S. aureus that produce SEA and can
      serve a confirmatory role in determining the presence of SEA in food samples. The
      assays were tested in two real-time PCR formats, using either dye-labeled DNA
      probes corresponding to each primer set that are degraded by the 5' exonuclease
      activity of Taq polymerase, or a PCR master mix that contains the DNA-binding dye
      SYBR Green. In both formats the assays have a limit of detection of between 1 and
      13 copies of a S. aureus genome that contains a copy of entA. Neither assay cross
      reacted with genomic DNA isolated from other strains of S. aureus or other
      species.

PMID- 16786249
TI  - Improvement of biohydrogen production under decreased partial pressure of H2 by
      Enterobacter cloacae.
AB  - When the partial pressure of H(2) was decreased by lowering the total pressure in
      the headspace of the reactor in a batch fermentation process from 760 mm Hg to
      380 mm Hg containing Enterobacter cloacae, the molar yield of H(2) increased from
      1.9 mol to 3.9 mol H(2)/mol glucose. The maximum production rate was 0.017 mmol
      H(2)/h l at 380 mm Hg. The lag period as well as total batch time of H(2)
      production decreased using a decreased partial pressure.

PMID- 16786250
TI  - Anti-hepatitis B activities of ganoderic acid from Ganoderma lucidum.
AB  - Ganoderic acid, from Ganoderma lucidum, at 8 microg/ml inhibited replication of
      hepatitis B virus (HBV) in HepG2215 cells over 8 days. Production of HBV surface
      antigen and HBV e antigen were 20 and 44% of controls without ganoderic acid.
      Male KM mice were significantly protected from liver injury, induced with carbon
      tetrachloride, by treatment with ganoderic acid at 10 mg and 30 mg/kg x d (by
      intravenous injection) 7 days. Ganoderic acid at the same dosage also
      significantly protected the mice from liver injury induced by M. bovis BCG plus
      lipopolysaccharide (from Escherichia coli 0127:B8).

PMID- 16786251
TI  - Enhancement of transient gene expression by fed-batch culture of HEK 293 EBNA1
      cells in suspension.
AB  - Enhanced green fluorescence protein (GFP) and erythropoietin (EPO) were used as
      reporters to assess and improve transient gene expression in HEK 293 EBNA1 cells.
      The production of EPO only lasted 3 days and reached 18.1 mg/l in suspension
      cultures in 1 l batch bioreactors. However, GFP expression examined in well-plate
      experiments persisted for 12 days in transfected cells but decreased rapidly
      within the next 15 days. These results suggest that the retaining of a plasmid in
      cells may not be a limiting factor for protein expression in large-scale
      transient transfection. To improve cell maintenance and protein expression, a fed
      batch culture was performed using an enriched medium, a mixture of equal volumes
      of 293 SFM II medium and a 5 x amino acid solution prepared based on DMEM/F12
      medium formula. EPO reached 33.6 mg/l, representing 86% increase over that of the
      batch culture. Moreover, the total amount of EPO produced was increased by 165%
      in view of the volume increase in the fed-batch culture. The serum-free medium
      used in this work enables cells growing well and transfection without medium
      change. Thus, the process reported here is simple and easy to scale up.

PMID- 16786252
TI  - Comparison of proprioceptive functions between computerized proprioception
      facilitation exercise and closed kinetic chain exercise in patients with knee
      osteoarthritis.
AB  - AIM: The aim of this study was to compare proprioceptive function between
      computerized proprioception facilitation exercise (CPFE) and closed kinetic chain
      exercise (CKCE) for knee osteoarthritis. DESIGN: Randomized-controlled. SETTING:
      Kinesiology laboratory. PATIENTS: Eighty-one patients with bilateral knee
      osteoarthritis were randomly assigned to CPFE, CKCE, and control groups.
      INTERVENTION: Both exercise groups underwent an 8-week program of three sessions
      per week. The control group received no training. The CPFE program included a 20
      min computer game to be played by the trained foot of the subject. CKCE included
      10 sets of 10 repetitions of repeated knee extension and flexion with resistance
      of 10-25% of body weight. MAIN OUTCOME MEASURES: Absolute reposition error,
      functional score, walking speed, and knee muscle strength were assessed with an
      electrogoniometer, the physical function subscale of Western Ontario and McMaster
      Osteoarthritis Index, a CASIO stopwatch, and a Cybex 6000 dynamometer before and
      after the 8-week period. RESULTS: The results of this study showed that both CPFE
      and CKCE were effective in improving joint position sense, functional score,
      walking speed, and muscle strength. Furthermore, CKCE showed greater effect in
      increasing knee extensor torque in patients with knee osteoarthritis. CONCLUSION:
      Clinical effects of CPFE were the same as those of CKCE except for knee extensor
      torque. The increase in knee extensor torque in CPFE patients was not as great as
      that seen in CKCE patients.

PMID- 16786253
TI  - Slow-stimulated multifocal ERG in high- and normal-tension glaucoma.
AB  - PURPOSE: To study the ability and sensitivity of the slow stimulation multifocal
      ERG (mfERG) to detect glaucomatous damage. METHODS: Right eyes of 20 patients
      with normal-tension glaucoma (NTG), 15 patients with high-tension glaucoma (HTG)
      and 15 healthy volunteers underwent testing with the mfERG (VERIS 4.1). The
      central 50 degrees of the retina were stimulated by 103 hexagons (m-sequence:
      2(13)-1, Lmax: 100 cd/m(2), Lmin: 1 cd/m(2), background: 50 cd/m(2)). Each m
      sequence step was followed by 3 black frames (Lmax: < 1 cd/m(2)). Five response
      averages of the first order response component (KI) were analyzed: the central
      7.5 degrees and the 4 adjoining quadrants. The amplitudes from the first minimum,
      N1, to the first maximum, P1, and from P1 to the second minimum, N2, were
      analyzed as well as the latencies of N1, P1, N2 and the latencies of 3 multifocal
      oscillatory potentials (mfOPs) with their maxima at about 73, 80 and 85 ms.
      RESULTS: For each parameter the percentage of deviation from the mean of the
      control group was calculated. These values were then added for each individual to
      form a deviation index (DI). Seventeen patients (85.0%) with NTG and 3 patients
      (20.0%) with HTG showed a DI outside the normal range. The major changes were
      observed in the mfOPs of the NTG patients. MfOPs were then selectively filtered
      at 100-300 Hz and their scalar product was analyzed over an epoch of 68-105 ms.
      This confirmed that mfOPs differed significantly from the control in the central
      7.5 degrees and, for NTG, in the nasal field. With a logistic regression analysis
      the mfOPs had a sensitivity to differentiate 85% of the NTG patients and 73% of
      the HTG patients from normal. CONCLUSIONS: Under these conditions, the slow
      stimulated mfERG can detect glaucomatous dysfunction in NTG (85.0%). The
      differences observed between NTG and HTG are in support of a different underlying
      pathomechanism.

PMID- 16786254
TI  - Copper concentration of liver tissue under long-term copper-histidine therapy in
      a patient with Menkes disease.
AB  - Copper-histidine is the treatment of choice in Menkes disease but bears the
      potential risk of copper overload and induced liver cirrhosis. We report normal
      copper concentrations of liver tissue over an 8-year treatment period with copper
      histidine.

PMID- 16786255
TI  - Dietary intervention and oxidative phosphorylation capacity.
AB  - Secondary deterioration of mitochondrial function has been reported in patients
      with anorexia and cancer-related malnutrition. Inadequate nutrition, failure to
      thrive and feeding problems are also common symptoms in children with primary
      oxidative phosphorylation defects. As a standard intervention protocol we advise
      an age-appropriate diet and energy intake in our patients diagnosed with a
      mitochondrial dysfunction. By comparing the results of the first and the second
      samples from a group of children who underwent repeated muscle biopsies, we
      observed biochemical improvement in the mitochondrial function in 7 out of 10
      patients following dietary advice and intervention. We suggest evaluating the
      nutritional state by interpretation of the skeletal muscle biochemistry in
      patients with a suspected oxidative phosphorylation defect. Since an insufficient
      dietary intake could play a role in secondary mitochondrial dysfunction,
      nutritional intervention should be performed prior to the biopsy. On the other
      hand, our data suggest that optimizing the nutritional and energy intake might
      also improve the utilization of the residual mitochondrial energy-generating
      capacity in patients with primary oxidative phosphorylation defects.

PMID- 16786256
TI  - Dietary treatment in adult-onset type II glycogenosis.
AB  - Eight patients with adult-onset type II glycogenosis (GSD II), all carrying the
      IVS1-13T<G mutation, were treated with high-protein isocaloric diet for 3 years.
      We evaluated the usefulness of this approach through the assessment of the
      skeletal muscles (by manual muscle testing, quantitative isokinetic exercise, and
      muscle MRI) and the respiratory function (by spirometry). Three patients with
      mild or moderate disease severity refused the diet and were still monitored for
      comparison: they showed clinical (2 patients) or clinicoradiological (1 patient)
      progression of muscle weakness, while respiratory function remained unchanged.
      Among the patients accepting the dietary treatment, muscle strength remained
      unchanged, as did the degree of fatty infiltration and atrophy as assessed by
      muscle MRI; respiratory function worsened in 2/5 patients with severe baseline
      respiratory dysfunction. High-protein diet may stabilize disease progression at
      the skeletal muscles, but does not produce significant clinical improvements;
      moreover, the usefulness of this approach in patients with severe respiratory
      disease seems questionable.

PMID- 16786257
TI  - Anomalous origin of the right vertebral artery from the ascending aorta in the
      presence of an aberrant right subclavian artery.
AB  - We present a case of a 63-year-old man who was admitted to the hospital due to an
      acute coronary syndrome. Angiographic and magnetic resonance angiography
      examination showed an abnormal right vertebral artery originating from the
      ascending aorta, just above the left coronary sinus Valsalva in addition to
      aberrant retro-esophageal right subclavian artery. The variations and the
      incidence of various abnormal origins of the right vertebral artery are also
      reviewed.

PMID- 16786258
TI  - Five chambered heart: a case report and brief review of literature.
AB  - We present a patient with chest pain and suspicious findings in
      electrocardiography and myocardial perfusion scintigraphy for myocardial
      ischemia. Coronary angiography and then echocardiography and magnetic resonance
      imaging revealed a dilated left anterior descending coronary artery, which has
      fistulous communication with a large, separate chamber that occupies the infero
      apical interventricular septum. This is a challenging congenital anomaly for a
      clinician in many aspects, which are discussed in the report.

PMID- 16786259
TI  - Evaluation of multiple coronary artery aneurysms in Kawasaki's disease by whole
      heart non-contrast enhanced MRI.
AB  - We describe a patient with history of an acute coronary syndrome. Cardiovascular
      magnetic resonance (CMR) was used for the assessment of coronary artery status
      using a high-resolution whole heart coronary artery imaging sequence, cardiac
      function at rest and detection of myocardial fibrosis using delayed enhancement.
      In the current case there were multiple giant aneurysms, one with evidence of
      thrombosis in combination with wall motion abnormalities and late enhancement in
      the myocardial segments supplied by this coronary artery.

PMID- 16786260
TI  - Applicability of Coriolopsis rigida for biodegradation of polycyclic aromatic
      hydrocarbons.
AB  - Laccase was produced by Coriolopsis rigida using barley bran as substrate in
      solid-state fermentation (SSF) and also by submerged fermentation (SmF). The best
      results were obtained in SSF with twice the amount of laccase production. Laccase
      could be produced from repeated batch cultures of SSF over 30 days. The laccase
      degraded several polycyclic aromatic hydrocarbons (PAHs) in vivo and in vitro.
      The addition of an effective mediator, 1-hydroxybenzotriazol (50 microM), during
      in vitro treatment increased the degradation rate.

PMID- 16786261
TI  - Effect of a short contact time with lees on volatile composition of Airen and
      Macabeo wines.
AB  - Volatile compounds were analyzed in Airen and Macabeo wines at the end of the
      alcoholic fermentation and after a short time contact with wine lees. The
      concentration of 34 analyzed compounds, with the exception of hexyl acetate,
      linalool, ss-ionone and farnesol, increased significantly after contact with lees
      in Airen wines. Esters and terpenic compounds decreased significantly in Macabeo
      wines after contact with lees. The contact with lees could be considered as
      favourable in Airen wines to improve the aroma quality.

PMID- 16786262
TI  - Recovery of nuclease produced by Lactococcus lactis using expanded bed ion
      exchange chromatography.
AB  - Expanded bed-ionic exchange chromatography (EB-IEC) was used for the recovery and
      purification of recombinant staphylococcal nuclease secreted by Lactococcus
      lactis. At the end of the fermentation process, the nuclease activity reached 39
      U ml(-1). The EB-IEC performances were firstly evaluated with clarified culture
      broth. The isocratic elution with 0.5 M NaCl led to approximately 80% of nuclease
      recovery. Proceeding with 3-fold bed expansion resulted in a reduction of the
      resin capacity by a factor of 32% compared to the process in a packed bed
      configuration. Simplification of the early purification steps was reached by
      loading immediately the unclarified culture broth previously diluted to reduce
      conductivity. Presence of Cells did not affect the chromatography performances
      resulting in 55-fold purification with the same yield.

PMID- 16786263
TI  - Verticillium lecanii spore formulation using UV protectant and wetting agent and
      the biocontrol of cotton aphids.
AB  - Verticillium lecanii spores (10(8 )spores ml(-1)) suspended in 1% (w/v)
      montmorillonite SCPX-1374 and 1% (w/v) of the wetting agent, EM-APW#2, which is a
      polyoxyethylene, had approx. 80% survival after exposure to UV-C for 30 min and
      about 93% after exposure to UV-B for 6 h. In greenhouse testing, cotton aphid
      densities increased 14-fold over their initial density in 15 d without spore
      application. However, initial cotton aphid densities were decreased by 60% of the
      initial level when plants were treated with the spore formulation.

PMID- 16786264
TI  - Salicylic acid enhances Jaceosidin and Syringin production in cell cultures of
      Saussurea medusa.
AB  - Addition of 20 muM salicylic acid to Saussurea medusa cell cultures at day 6
      resulted in jaceosidin and syringin productions up to 95 mg l(-1 )and 631 mg l(
      1) which were, respectively, about 2.5- and 2.7-fold higher than in the control.
      The biomass was increased from 8 to 12 g l(-1). Expression of chalcone synthase
      gene (chs) increased sharply after 12 h treatment and was sustained up to 48 h;
      chalcone isomerase gene (chi) expression reached a peak at 24 h and decreased
      after 48 h; and phenylalanine ammonia-lyase activity increased by 7.5-fold (96 U
      mg(-1) protein) higher than in the control after 24 h. These results indicate
      that salicylic acid enhances the production of jaceosidin and syringin which is
      accompanied by induction of the related phenylpropanoid biosynthetic enzymes.

PMID- 16786265
TI  - Activation of a refolded, berberine-specific, single-chain Fv fragment by
      addition of free berberine.
AB  - A single-chain variable fragment (scFv) specific for berberine was produced in
      Escherichia coli. The anti-berberine scFv gene was cloned from hybridoma 1D5-3B-7
      producing the monoclonal antibody. The variable regions of the heavy (V(H)) and
      light chain (V(L)) genes were connected with a flexible linker using an assembly
      PCR. The V(H)-linker-V(L) gene was inserted into a plasmid, pET28a (+), then
      overexpressed in E. coli BL21 (DE3). The active of the scFv by refolding based on
      stepwise dialysis methods and an artificial chaperone was determined by direct
      and competitive enzyme-linked immunosorbent assay (ELISA). The results of direct
      ELISA showed that the anti-berberine scFv retained specific binding activity to
      berberine. In competitive ELISA, however, activity was increased depending on the
      concentration of berberine.

PMID- 16786266
TI  - Expression, renaturation and simultaneous purification of recombinant human stem
      cell factor in Escherichia coli.
AB  - Recombinant human stem cell factor (rhSCF) was produced as an inclusion body by
      Escherichia coli DH5alpha grown in a 5 l fermentor. Inclusion bodies of rhSCF
      were purified and solubilized in urea solution, then renatured with simultaneous
      purification using a high performance hydrophobic interaction chromatographic
      (HPHIC) squat column. The refolded rhSCF had a purity of 94% and a bioactivity of
      1.2 x 10(6 )IU mg(-1)of rhSCF protein. The method described is fast and simple to
      implement.

PMID- 16786267
TI  - Screen-less expanded bed column: new approach for the recovery and purification
      of a malaria transmission blocking vaccine candidate from Pichia pastoris.
AB  - An experimental malaria transmission blocking vaccine antigen, Pfs25H, expressed
      and secreted from Pichia pastoris was recovered and purified using a screenless
      expanded bed column equipped with a rotating fluid distribution system. This
      column was able to accommodate feed stock, containing 30% biomass, at a flow rate
      of 300-400 cm/h without affecting column stability. This capability is three
      times higher than the capability of the expanded bed column currently in use,
      which is equipped with a perforated plate fluid distribution system; this design
      could accommodate biomass concentrations of only up to 10%. The screen-less
      design did not affect the binding capacity, purification level or process yield
      and, therefore, shorten the process. Purified Pfs25H of 6.4 g were recovered from
      37 l of Pichia pastoris culture in one step.

PMID- 16786268
TI  - Molecular cloning and expression of perhydrolase genes from Pseudomonas
      aeruginosa and Burkholderia cepacia in Escherichia coli.
AB  - Two bacterial perhydrolase genes, perPA and perBC, were cloned from Pseudomonas
      aeruginosa and Burkholderia cepacia, respectively, using PCR amplification with
      primers designed to be specific for conserved amino acid sequences of the already
      known perhydrolases. The amino acid sequence of PerPA was identical to a putative
      perhydrolase of P. aeruginosa PAO1 genome sequences, whereas PerBC of B. cepacia
      was a novel bacterial perhydrolase showing similarity of less than 80% with all
      other existing perhydrolases. Most importantly, the perPA gene was expressed as a
      soluble intracellular form to an extent of more than 50% of the total protein
      content in Escherichia coli. Two perhydrolase enzymes were confirmed to exhibit
      the halogenation activity towards Phenol Red and monochlorodimedone. These
      results suggested that we successfully obtained the newly identified members of
      the bacterial perhydrolase family, expanding the pool of available perhydrolases.

PMID- 16786269
TI  - Cloning and expression of human stem cell factor fused with thrombopoietin
      mimetic peptide in Escherichia coli.
AB  - Thrombopoietin (TPO) acts synergistically with stem cell factor (SCF) in
      hematopoiesis and megakaryopoiesis. In this work, we designed the expression of
      SCF fused with the monomer or the dimer of TPO mimetic peptide through a flexible
      peptide linker. The recombinant fusion proteins were produced in E. coli DH5alpha
      at up to 25% of total cell proteins. The resultant inclusion bodies were refolded
      by dilution and purified by ion-exchange chromatography. Subsequent biological
      activity assays showed that the fusion proteins exhibited higher potency than
      recombinant human SCF, indicating that they have a potential role for
      pharmaceutical applications.

PMID- 16786270
TI  - A novel dual peroxisome proliferator-activated receptors alpha and gamma agonist
      with beneficial effects on insulin resistance and lipid metabolism.
AB  - Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are key
      regulators of lipid homeostasis and insulin resistance. In this study we show
      that a novel compound, 3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}- 2
      [2-(2-nitro-phenoxy)-acetyl amino]-propionic acid (O325H), is an agonist with
      dual effect on PPARalpha/gamma by using dual-luciferase reporter gene assay. By
      activating PPARalpha and PPARgamma simultaneously, O325H promotes pre-adipocyte
      differentiation and up-regulates the expression of glucose and lipid metabolic
      target genes. In diabetic mice, administration of O325H at 10 mg/kg decreases the
      blood lipid and glucose levels. Therefore, O325H has dual action on PPARalpha and
      PPARgamma and is a promising agent for the amelioration of lipid metabolic
      disorders and diabetes associated with insulin resistance.

PMID- 16786271
TI  - High-level expression of basic fibroblast growth factor in transgenic soybean
      seeds and characterization of its biological activity.
AB  - The glycinin G1 gene encodes a soybean seed storage protein accumulating at a
      high level. We have used the G1 promoter to confer seed-specific expression of
      human basic fibroblast growth factor (bFGF) in transgenic soybeans. The coding
      region of 18 kDa bFGF was fused to the promoter or promoter-signal peptide
      sequence of G1 gene, and transferred into soybean. Analysis of transgenic plants
      demonstrated that bFGF transcript or protein was confined to the seeds. The
      highest level of bFGF accumulation in the seeds reached up to 2.3% of total
      soluble protein. The soybean-derived bFGF was biologically active as confirmed by
      its mitogenic activity on Balb/c 3T3 cells, and exhibited other properties
      identical to native bFGF. We also observed a seed-specific expression of beta
      glucuronidase driven by the G1 promoter. These results indicated that the G1
      promoter contains essential cis-elements for seed-specific expression, and thus
      can be used for expression of pharmaceutical proteins in soybean seeds.

PMID- 16786272
TI  - One-pot microbial synthesis of 2'-deoxyribonucleoside from glucose, acetaldehyde,
      and a nucleobase.
AB  - A one-pot enzymatic synthesis of 2'-deoxyribonucleoside from glucose,
      acetaldehyde, and a nucleobase was established. Glycolysis by baker's yeast
      (Saccharomyces cerevisiae) generated ATP which was used to produce D: 
      glyceraldehyde 3-phosphate production from glucose via fructose 1,6-diphosphate.
      The D: -glyceraldehyde 3-phosphate produced was transformed to 2'
      deoxyribonucleoside via 2-deoxyribose 5-phosphate and then 2-deoxyribose 1
      phosphate in the presence of acetaldehyde and a nucleobase by deoxyriboaldolase,
      phosphopentomutase expressed in Escherichia coli, and a commercial nucleoside
      phosphorylase. About 33 mM 2'-deoxyinosine was produced from 600 mM glucose, 333
      mM acetaldehyde and 100 mM adenine in 24 h. 2'-Deoxyinosine was produced from
      adenine due to the adenosine deaminase activity of E. coli transformants.

PMID- 16786273
TI  - Development of a fiber optic enzymatic biosensor for 1,2-dichloroethane.
AB  - There is a significant need for devices capable of measuring water contaminant
      concentrations in situ--continuously, rapidly, and without reagents, extraction,
      or other pretreatment. Toward this goal, we constructed and tested fiber optic
      biosensors for measurement of 1,2-dichloroethane (DCA) in aqueous solutions. The
      biocomponent was the haloalkane dehalogenase, DhlA, in whole cells of
      Xanthobacter autotrophicus GJ10. These cells were immobilized in calcium alginate
      on the tip of a fiber optic fluoresceinamine-based pH optode. The resulting
      biosensor could quantify DCA at 11 mg/l and had a linear response up to at least
      65 mg/l. Total signal change was reached in 8-10 min, and measurements were
      reproducible (SE <9%). The sensor's small size, potential for remote operation,
      and low cost make it of interest for further development.

PMID- 16786274
TI  - Quantitative comparison of the signals of an electrochemical bioactivity sensor
      during the cultivation of different microorganisms.
AB  - The microbial activity of different microorganisms was determined by means of an
      electrochemical bioactivity sensor (BAS). The BAS is based on a biofuel cell and
      was used for analytical purposes. Online determination of microbial activity
      using the BAS demonstrated that when different microorganisms with different
      metabolic pathways were cultivated, a distinct activity signal was detectable
      with all organisms applied. Furthermore, the results permitted a quantitative
      comparison of the BAS signals. Among other findings it was shown that the
      quotient of the BAS signal and the utilized glucose varied from 0.16-29.08 mV g(
      1), the quotient of the maximum BAS signal and the released energy of the
      reaction exhibited a lower variation of 0.07-0.19 mV kJ(-1). Furthermore it was
      demonstrated that the highest BAS signals could be measured during anaerobic E.
      coli fermentations, the reason being the formation of electroactive fermentation
      products, such as formic acid and H(2).

PMID- 16786275
TI  - Over-production of beta-carotene from metabolically engineered Escherichia coli.
AB  - To produce recombinant beta-carotene in vitro, synthetic operons encoding genes
      governing its biosynthesis were engineered into Escherichia coli. Constructs
      harboring these operons were introduced into either a high-copy or low-copy
      cloning vector. beta-Carotene production from these recombinant E. coli cells was
      either constitutive or inducible depending upon plasmid copy number. The most
      efficient beta-carotene production was with the low-copy based vector. The
      process was increased incrementally from a 5 l to a 50 l fermentor and finally
      into a 300 l fermentor. The maximal beta-carotene yields achieved using the 50 l
      and 300 l fermentor were 390 mg l(-1) and 240 mg l(-1), respectively, with
      overall productivities of 7.8 mg l(-1) h(-1) and 4.8 mg l(-1) h(-1).

PMID- 16786276
TI  - Expression and aggregation of recombinant human consensus interferon-alpha mutant
      by Pichia pastoris.
AB  - A recombinant human consensus interferon-alpha mutant (cIFN) was expressed in
      Pichia pastoris. The maximum dry cell weight, cIFN concentration and antiviral
      activity were 160 g l(-1), 1.24 g l(-1) and 4.1 x 10(7) IU ml(-1), respec tively.
      The cIFN secreted into the medium was in the form of aggregates dominantly by non
      covalent interaction and partially by disulphide bond. When the fermentation
      supernatant was disaggregated with 6 M guanidine hydrochloride, the antiviral
      activity of cIFN achieved 2.2 x 10(8) IU ml(-1).

PMID- 16786277
TI  - Enhancement and selective production of oligomycin through inactivation of
      avermectin's starter unit in Streptomyces avermitilis.
AB  - Oligomycin and its analogues, produced by Streptomyces avermitilis and other
      actinomycetes, are of interest for their potent and selective biological
      activities. PCR-mediated gene replacement, targeting bkdF, one of avermectin's
      starter unit encoding genes in S. avermitilis, was performed to yield an
      oligomycin producer, BIB0423. The engineered strain produced oligomycin A at 2.3
      mg/ml compared to the wild type strain at 0.1 mg/ml. This resulting mutant was
      genetically stable and should be useful for the industrial production of
      oligomycin.

PMID- 16786278
TI  - Bioaffinity based oriented immobilization of stem bromelain.
AB  - Bromelain is a basic, 23.8 kDa thiol proteinase obtained from stem of the
      pineapple plant (Ananas comosus) and is unique in containing a single
      oligosaccharide chain attached to the polypeptide. This property allowed its
      affinity binding and favorable orientation on a Sepharose support pre-coupled
      with the lectin, concanavalin A (Con A). For comparison, bromelain was also
      immobilized by covalently coupling to the CNBr-activated Sepharose. The
      preparation obtained was more resistant to thermal inactivation as evident from
      the retention of over 50% activity after incubation at 60 degrees C for 100 min
      (as compared to 20% retained by the native enzyme and 30% retained by the
      covalently immobilized enzyme), exhibited a broader pH-activity profile with the
      enzyme retaining over 60% activity at pH 11 (as compared to over 25% retained by
      native and the enzyme immobilized covalently). The native, covalently-coupled and
      affinity-bound bromelains had apparent K (m) values of 1.1, 2 and 0.54 mg/ml,
      respectively using casein as the substrate. The V (max) values remained
      unaffected on immobilization.

PMID- 16786279
TI  - Molecular cloning and expression of a cDNA encoding Lon protease from rice (Oryza
      sativa).
AB  - The ATP-dependent Lon protease is a highly conserved enzyme that is present in
      archeae, eubacteria, and eukaryotes, and plays an important role in intracellular
      protein degradation. We have isolated a Lon protease gene, OsLon1, from Oryza
      sativa. The cDNA contained a 2,655 bp ORF. Comparative analysis showed that
      OsLon1 shared significant similarity with the previously reported Lon proteases
      from maize, Arabidopsis, human, and bacteria. Tissue expression pattern analysis
      revealed that OsLon1 was highly expressed in young leaves, mature leaves, and
      leaf sheaths but only weakly in young roots, mature roots, and young panicles.
      The OsLon1 gene was successfully expressed in E. coli and the detected protein
      size, about 120 kDa, matched the expected molecular mass of the His-tagged OsLon1
      protein.

PMID- 16786280
TI  - Nucleotide mutations in purA gene and pur operon promoter discovered in guanosine
      and inosine-producing Bacillus subtilis strains.
AB  - The promoter region of the pur operon, which contains 12 genes for inosine
      monophosphate biosynthesis from phosphoribosylpyrophosphate, and the purA gene,
      encoding the adenylosuccinate synthetase, were compared among wild-type and three
      purine-producing Bacillus subtilis strains. A single nucleotide deletion at
      position 55 (relative to translation start site) in purA gene was found in a high
      inosine-producing strain and in a high guanosine-producing strain, which
      correlates with the absence of adenylosuccinate synthetase activity in these
      strains. Within the pur operon promoter of high guanosine-producing strain, in
      addition to a single nucleotide deletion in PurBox1 and a single nucleotide
      substitution in PurBox2, there were 4 substitutions in the flanking region of the
      PurBoxes and 32 nucleotide mutations in the 5' untranslated region. These
      mutations may explain the purine accumulation in purine-producing strains and be
      helpful to the rational design of high-yield recombinant strains.

PMID- 16786281
TI  - Diplectanids (Monogenea) parasitic on the gills of the coralgroupers Plectropomus
      laevis and P. leopardus (Perciformes, Serranidae) off New Caledonia, with the
      description of five new species and the erection of Echinoplectanum n. g.
AB  - Echinoplectanum n. g. is erected for diplectanids which have a male copulatory
      organ comprising a tubular sclerotised penis with a muscular reservoir at its
      proximal extremity and an protrusible cirrus, often with spiny ridges, at its
      distal extremity, and a female copulatory organ comprising a sclerotised vaginal
      sac, often with two thin tubes. All species have similar squamodiscs made of rows
      of rodlets, with the central rows forming closed circles, and haptoral parts with
      a similar shape but different measurements; they are distinguished on the basis
      of the size and morphology of the male copulatory organ and sclerotised vagina.
      Five new species are included in Echinoplectanum and are all parasites of
      coralgroupers, Plectropomus spp., off New Caledonia, South Pacific. Two are from
      P. laevis (Lacepede): E. laeve n. sp. (type-species) has a large elongate penis,
      53[Formula: see text]m in length, a cirrus with spiny ridges and a spherical
      vagina with two long thin tubes; and E. chauvetorum n. sp. has a large elongate
      penis, 51[Formula: see text]m in length, a cirrus with thin spiny ridges, and a
      pear-shaped vagina with two short thin tubes. Three species are from P. leopardus
      (Lacepede): E. leopardi n. sp. has an elongate penis, 36[Formula: see text]m in
      length, an unspiny cirrus and a triangular vagina; E. pudicum n. sp. has a very
      small elongate penis 14[Formula: see text]m in length and no visible vagina; and
      E. rarum n. sp. has a short thick penis 18[Formula: see text]m in length and a
      ring-shaped vagina with two thin tubes. In addition, Diplectanum plectropomi
      Young, 1969, from P. maculatus off Western Australia, and D. echinophallus Euzet
      & Oliver, 1965 from Epinephelus marginatus in the Mediterranean Sea and Senegal,
      West Africa, both herein redescribed from the type-specimens, are transferred to
      Echinoplectanum, as E. plectropomi n. comb. and E. echinophallus n. comb.,
      respectively. Six of the seven species of Echinoplectanum are parasitic in
      members of Plectropomus from the South West Pacific, but one (E. echinophallus)
      is a parasite of Epinephelus marginatus and has been recorded only from the
      Mediterranean and East Atlantic; it is suggested that Echinoplectanum is
      associated with Plectropomus, a basal genus among the epinephelines, and that
      host-switching to Epinephelus marginatus occurred, whose distribution extends
      from Europe to the Indian Ocean. Morphological characteristics of the copulatory
      organs suggest that a "chastity belt versus spiny penis" sperm competition
      pattern prevails in Echinoplectanum spp.

PMID- 16786282
TI  - Laticola dae n. sp. (Monogenea: Diplectanidae) from Epinephelus maculatus
      (Perciformes: Serranidae) off New Caledonia.
AB  - Laticola dae n. sp. is described from specimens collected from the gill-filaments
      of the highfin grouper Epinephelus maculatus, a coral reef fish caught off
      Noumea, New Caledonia, South Pacific. The species is characterised by a spoon
      shaped sclerotised male copulatory organ, with four thin walls and 73-[Formula:
      see text]m in outer length, and a sclerotised vagina in form of a disc, 16
      [Formula: see text]m in diameter, with a smaller hemisphere on one side. Laticola
      Yang et al., 2006 was described to accommodate diplectanids from Lates calcarifer
      (Centropomidae); this is the first Laticola described from a serranid. Other
      diplectanids, including several species of Pseudorhabdosynochus Yamaguti, 1958,
      were also found on the same species of fish; specimens of L. dae represented
      about half of the diplectanids collected; all other species were rare.

PMID- 16786283
TI  - Monogeneans on native and introduced freshwater fishes from Cuba with the
      description of a new species of Salsuginus Beverley-Burton, 1984 from Limia
      vittata (Poeciliidae).
AB  - During a parasitological survey carried out between March and September 2003 in
      Cuba, the following monogeneans were found on the gills of freshwater fishes:
      Salsuginus cubensis n. sp. on the Cuban molly Limia vittata Guichenot
      (Poeciliidae); Cichlidogyrus sclerosus Paperna & Thurston, 1969 and C. tilapiae
      Paperna, 1960 on the African cichlid Tilapia rendalli Boulenger (Cichlidae);
      Haplocleidus dispar Mueller, 1936 and Pterocleidus acer Mueller, 1936 (all
      Dactylogyridae) on the sunfish Lepomis macrochirus Rafinesque (Centrarchidae)
      (new geographical records); and Gyrodactylus sp. (Gyrodactylidae) on the biajaca
      Nandopsis tetracanthus Valenciennes (Cichlidae) (new host and geographical
      record). Salsuginus cubensis differs from all other species of the genus in the
      size and morphology of the copulatory complex. The occurrence of C. sclerosus, C.
      tilapiae, H. dispar and P. acer in their respective hosts is due to the
      introduction of these hosts to Cuba. A review of the species composition of the
      Monogenea in native and introduced freshwater fish from Cuba is presented and the
      zoogeographical distribution of the species found is briefly discussed.

PMID- 16786284
TI  - Nomimoscolex pertierrae n. sp. (Eucestoda: Proteocephalidea), a parasite of
      Pseudoplatystoma corruscans (Siluriformes: Pimelodidae) in Brazil and
      redescription of N. sudobim Woodland, 1935, a parasite of P. fasciatum.
AB  - The cestode Nomimoscolex sudobim Woodland, 1935 (Proteocephalidea) is redescribed
      on the basis of its type-specimens and recently collected material found in the
      intestine of the 'sudobim' Pseudoplatystoma fasciatum (Siluriformes: Pimelodidae)
      (type-host), from the Amazon River (near the type-locality). Nomimoscolex
      pertierrae n. sp. is described from the 'surubi' Pseudoplatystoma corruscans from
      the Parana River around Porto Rico. Among fifteen known Nomimoscolex species,
      only N. sudobim possess a cortical uterus in combination with osmoregulatory
      canals some distance internal to the proglottis margins, as in N. pertierrae n.
      sp. N. pertierrae differs from N. sudobim, which exhibits the most similarity
      with the former species, in the morphology of the scolex, the size and unusual
      shape of microtriches (slender digitiform) on the internal and marginal regions
      of the suckers, and in the lower mean number of testes [(114 in N. pertierrae,
      ranging between 216 (recently collected material) and 240 (type-material) in N.
      sudobim)]. The material described as N. sudobim by Pavanelli & Rego (1992) from
      the intestine of P. corruscans is considered to be N. pertierrae. The utility of
      microtriches as characters for distinguishing between species is demonstrated in
      the clear differences in the shape of those of N. pertierrae and N. sudobim. The
      morphology of microtriches warrants more attention in future studies on the
      taxonomy of proteocephalidean cestodes.

PMID- 16786285
TI  - Anilocra pilchardi n. sp., a new parasitic cymothoid isopod from off Lebanon
      (Eastern Mediterranean).
AB  - Anilocra pilchardi n. sp. is described from several specimens collected mainly
      from clupeiform fishes from off Lebanon. Various stages of the parasite are
      considered: ovigerous and non-ovigerous females, male and intramarsupial larvae.
      Taxonomic comments on the relationship of A. pilchardi to other congeneric
      species are given. A. pilchardi belongs to a particular group of Anilocra species
      previously known only from the Indo-Pacific Region.

PMID- 16786286
TI  - Three new species of Dactylogyrus Diesing, 1850 (Monogenea: Dactylogyridae) from
      the gills of the bala sharkminnow Balantiocheilos melanopterus (Cyprinidae) from
      Thailand.
AB  - Three new species of Dactylogyrus are described from the gills of the cyprinid
      fish Balantiocheilos melanopterus (Bleeker) imported from Thailand via the
      aquarium trade. They are D. coartatus n. sp., D. macrocolpius n. sp. and D.
      melanopteri n. sp. The double-bar species, D. coartatus n. sp. and D. melanopteri
      n. sp., are characterised by hooks that are markedly large in relation to the
      size of the anchors. Clip-like anchors with a sharply recurved, long point are a
      unique feature of D. coartatus n. sp. The single-bar species, D. macrocolpius n.
      sp., is characterised by having a copulatory organ composed of a spiral copulum
      and a medial accessory piece with thorns.

PMID- 16786288
TI  - Copy number of bean mitochondrial genes estimated by real-time PCR does not
      correlate with the number of gene loci and transcript levels.
AB  - Structural rearrangements characteristic for plant mitochondrial DNA often result
      in the appearance of genes in new genomic environments. The determination of the
      real number of gene copies is difficult since the in vivo structure of plant
      mitochondrial genomes is questionable. It is still uncertain whether the gene
      copy number regulates transcription in plant mitochondria. Using the real-time
      PCR technique we have quantified the copies of mitochondrial genes and their
      transcripts in four related Phaseolus vulgaris lines. We found low intergenomic
      variation both in the copy number of particular genes and the abundance of their
      transcripts, while the intragenomic differences between copy numbers and
      transcripts levels of various genes were much higher. Furthermore, we found that
      the appearance of a gene in a new location is not correlated with a proportional
      increase in its copy number estimated by real-time PCR. This observation seems to
      result from gene dosage compensation which is probably associated with the
      multimolecular plant mitochondrial genome structure and particularly with the
      recombinogenic activity of large repeats. Based on the relative gene copy numbers
      we propose the existence of two types of Phaseolus mitochondrial genomes: one
      associated with fertility and the other inducing cytoplasmic male sterility. We
      also show that there is no correlation between the observed number of copies of
      the analyzed genes and the steady-state level of their transcripts.

PMID- 16786290
TI  - Direct interaction between the tobacco mosaic virus helicase domain and the ATP
      bound resistance protein, N factor during the hypersensitive response in tobacco
      plants.
AB  - Plants cope with pathogens with distinct mechanisms. One example is a gene-for
      gene system, in which plants recognize the pathogen molecule by specified
      protein(s), this being called the R factor. However, mechanisms of interaction
      between proteins from the host and the pathogen are not completely understood.
      Here, we analyzed the mode of interaction between the N factor, a tobacco R
      factor, and the helicase domain (p50) of tobacco mosaic virus (TMV). To this end,
      domain dissected proteins were prepared and subjected to Agroinfiltration into
      intact leaves, followed by yeast two hybrid and pull-down assays. The results
      pointed to three novel features. First, the N factor was found to directly bind
      to the p50 of TMV, second, ATP was pre-requisite for this interaction, with
      formation of an ATP/N factor complex, and third, the N factor was shown to
      possess ATPase activity, which is enhanced by the p50. Moreover, we found that
      intra- and/or inter-molecular interactions take place in the N factor molecule.
      This interaction required ATP, and was disrupted by the p50. Based on these
      results, we propose a following model for the TMV recognition mechanism in
      tobacco plants. The N factor forms a complex with ATP, to which the helicase
      domain interacts, and enhances ATP hydrolysis. The resulting ADP/N factor complex
      then changes its conformation, thereby facilitating further interaction with the
      down-stream signaling factor(s). This model is consistent with the idea of
      'protein machine'.

PMID- 16786289
TI  - The Arabidopsis AtDi19 gene family encodes a novel type of Cys2/His2 zinc-finger
      protein implicated in ABA-independent dehydration, high-salinity stress and light
      signaling pathways.
AB  - The AtDi19 (drought-induced) gene family encodes seven hydrophilic proteins that
      contain two atypical Cys2/His2 (C2H2) zinc finger-like domains that are
      evolutionarily well-conserved within angiosperms suggesting a conserved and
      important function. Five of the seven Arabidopsis AtDi19-related:DsRed2 fusion
      proteins exhibited speckled patterns of localization within the nucleus as shown
      by transient expression analysis in Arabidopsis protoplasts. In contrast, AtDi19
      2:DsRed2 was present in the nucleus and cytoplasm, whereas AtDi19-4:DsRed2 was
      localized to the nuclear periphery. mRNA expression studies showed that AtDi19
      genes are ubiquitously expressed in Arabidopsis tissues, although some
      differences were observed. In seedlings, RT-PCR analyses showed that AtDi19-1 and
      AtDi19-3 steady-state transcript amounts were rapidly induced by dehydration,
      whereas transcript amounts for AtDi19-2 and AtDi19-4 increased in response to
      high-salt stress. In addition, the mRNA abundance of all the AtDi19-related gene
      family members was not regulated by ABA. These data, taken together, suggest that
      several AtDi19-related gene family members may function in ABA-independent,
      dehydration and salinity stress signaling pathways. However, they may also be
      regulated by other abiotic stimuli. AtDi19-7, for example, has been implicated in
      regulating light signaling and responses. Finally, we show that most AtDi19
      related proteins are phosphorylated in vitro by calcium-dependent protein kinases
      suggesting that this post-translational modification may be important for
      regulating the function of this novel protein family.

PMID- 16786291
TI  - Spatial organisation of four enzymes from Stevia rebaudiana that are involved in
      steviol glycoside synthesis.
AB  - The sweet steviol glycosides found in the leaves of Stevia rebaudiana Bert. are
      derived from the diterpene steviol which is produced from a branch of the
      gibberellic acid (GA) biosynthetic pathway. An understanding of the spatial
      organisation of the two pathways including subcellular compartmentation provides
      important insight for the metabolic engineering of steviol glycosides as well as
      other secondary metabolites in plants. The final step of GA biosynthesis, before
      the branch point for steviol production, is the formation of (-)-kaurenoic acid
      from (-)-kaurene, catalysed by kaurene oxidase (KO). Downstream of this, the
      first committed step in steviol glycoside synthesis is the hydroxylation of
      kaurenoic acid to form steviol which is then sequentially glucosylated by a
      series of UDP-glucosyltransferases (UGTs) to produce the variety of steviol
      glycosides. The subcellular location of KO and three of the UGTs involved in
      steviol glycoside biosynthesis was investigated by expression of GFP fusions and
      cell fractionation which revealed KO to be associated with the endoplasmic
      reticulum and the UGTs in the cytoplasm. It has also been shown by expressing the
      Stevia UGTs in Arabidopsis that the pathway can be partially reconstituted by
      recruitment of a native Arabidopsis glucosyltransferase.

PMID- 16786292
TI  - Characterizations of a hypomorphic argonaute1 mutant reveal novel AGO1 functions
      in Arabidopsis lateral organ development.
AB  - Genes that encode the ARGONAUTE (AGO) proteins make up a highly conserved family,
      and several members in the family have been defined to function in
      posttranscriptional gene silencing (PTGS) in plants, quelling in fungi and RNAi
      in animals. The Arabidopsis AGO1 gene has been demonstrated to be crucial in
      multiple RNA silencing pathways (PTGS, microRNA and trans-acting siRNA pathways);
      however, its biological functions do not seem to be fully addressed. Here we
      report characterizations of a new hypomorphic ago1 allele, ago1-37, and show
      novel AGO1 functions important in lateral organ development. We found that double
      mutants combining ago1-37 with asymmetric leaves1 (as1) or asymmetric leaves2
      (as2) produced more severe phenotypes than the single mutants, indicating that
      AGO1 genetically interacts with AS1 and AS2 for plant development. Similar to the
      previously characterized mutants rdr6, sgs3 and zippy, which are deficient in the
      trans-acting siRNA activity, ago1-37 also showed an earlier phase transition from
      juvenile to adult leaves. Moreover, based on the detailed phenotypic analyses of
      single and double mutant plants, we found that the AGO1 functions are required
      for repressing several class I KNOTTED1-like homeobox (KNOX) genes in leaves, and
      for specifying both adaxial and abaxial identities of the leaf and petal. Our
      results demonstrate several important AGO1 functions in plant lateral organ
      development.

PMID- 16786293
TI  - A LINE-type retrotransposon active in meristem stem cells causes heritable
      transpositions in the sweet potato genome.
AB  - We isolated a LINE-type retrotransposon, LIb, which showed high transposition
      activity in sweet potato callus. A copy transposed in the callus was 6303 bp in
      length and showed key features of a LINE element. Apparently full-length copies
      sharing the 5' UTR sequence with the 6303-bp copy increased dramatically in the
      callus as several original copies in the sweet potato genome. These apparently
      full-length copies had almost identical sequences to other transposed copies,
      many of which were truncated at the 5' end upon transposition. These results
      indicate that active LIb is confined to a single LINE family, and that members
      containing a long functional 5' UTR are present in limited numbers in the sweet
      potato genome. This is despite their copy numbers being estimated at over 100.
      The transcription of LIb was not completely suppressed, even in wild-type plants.
      Spontaneous transpositions were found among local variant lines of the cultivar
      Koukei14, from which the callus with high LIb activity was derived. Meristem
      culture of this cultivar appeared to facilitate transpositions of LIb in a
      mericlone plant. This is the first experimental demonstration of
      retrotransposition in a plant species without the imposition of cell
      differentiation. LIb transpositions appear to occur in single founder cells in
      the meristem because the LIb insertion was found throughout mericlone plant
      tissues. Transpositional activities in meristem cells might be essential
      characteristics of plant retrotransposons that cause heritable changes in host
      plant genomes and genetic systems.

PMID- 16786294
TI  - CASAR82A, a pathogen-induced pepper SAR8.2, exhibits an antifungal activity and
      its overexpression enhances disease resistance and stress tolerance.
AB  - Pepper SAR8.2 gene (CASAR82A) was previously reported to be locally or
      systemically induced in pepper plants by biotic and abiotic stresses. In this
      study, the physiological and molecular functions of the pepper SAR8.2 protein in
      the plant defense responses were investigated by generating Arabidopsis
      transgenic lines overexpressing the CASAR82A gene. The transgenic Arabidopsis
      plants grew faster than the wild-type plants, indicating that the CASAR82A gene
      was involved in plant development. The ectopic expression of CASAR82A in
      Arabidopsis was accompanied by the expression of the Arabidopsis pathogenesis
      related (PR)-genes including AtPR-1, AtPR-4 and AtPR-5. CASAR82A overexpression
      enhanced the resistance against infections by Pseudomonas syringae pv. tomato,
      Fusarium oxysporum f.sp. matthiolae or Botrytis cinerea. The transgenic plants
      also exhibited increased NaCl and drought tolerance during all growth stages.
      Moreover, the methyl viologen test showed that the transgenic plants were
      tolerant to oxidative stress. The purified recombinant CASAR82A protein and crude
      protein extracts of the transgenic plants exhibited antifungal activity against
      some phytopathogenic fungi, indicating that the enhanced resistance of the
      transgenic plants to fungal pathogen infection may be due to the antifungal
      effect of SAR8.2 protein.

PMID- 16786296
TI  - A microarray-based detection system for genetically modified (GM) food
      ingredients.
AB  - A multiplex DNA microarray chip was developed for simultaneous identification of
      nine genetically modified organisms (GMOs), five plant species and three GMO
      screening elements, i.e. the 35S promoter, the nos terminator and the nptII gene.
      The chips also include several controls, such as that for the possible presence
      of CaMV. The on-chip detection was performed directly with PCR amplified
      products. Particular emphasis was placed on the reduction of the number of PCR
      reactions required and on the number of primers present per amplification tube.
      The targets were biotin labelled and the arrays were detected using a
      colorimetric methodology. Specificity was provided by specific capture probes
      designed for each GMO and for the common screening elements. The sensitivity of
      the assay was tested by experiments carried out in five different laboratories.
      The limit of detection was lower than 0.3% GMO for all tests and in general
      around 0.1% for most GMOs. The chip detection system complies with the
      requirements of current EU regulations and other countries where thresholds are
      established for the labelling of GMO.

PMID- 16786295
TI  - Cyanide metabolism in higher plants: cyanoalanine hydratase is a NIT4 homolog.
AB  - Cyanoalanine hydratase (E.C. 4.2.1.65) is an enzyme involved in the cyanide
      detoxification pathway of higher plants and catalyzes the hydrolysis of beta
      cyano-L-alanine to asparagine. We have isolated the enzyme from seedlings of blue
      lupine (Lupinus angustifolius) to obtain protein sequence information for
      molecular cloning. In contrast to earlier reports, extracts of blue lupine
      cotyledons were found also to contain cyanoalanine-nitrilase (E.C. 3.5.5.4)
      activity, resulting in aspartic acid production. Both activities co-elute during
      isolation of cyanoalanine hydratase and are co-precipitated by an antibody
      directed against Arabidopsis thaliana nitrilase 4 (NIT4). The isolated
      cyanoalanine hydratase was sequenced by nanospray-MS/MS and shown to be a homolog
      of Arabidopsis thaliana and Nicotiana tabacum NIT4. Full-length cDNA sequences
      for two NIT4 homologs from blue lupine were obtained by PCR using degenerate
      primers and RACE-experiments. The recombinant LaNIT4 enzymes, like Arabidopsis
      NIT4, hydrolyze cyanoalanine to asparagine and aspartic acid but show a much
      higher cyanoalanine-hydratase activity. The two nitrilase genes displayed
      differential but overlapping expression. Taken together these data show that the
      so-called 'cyanoalanine hydratase' of plants is not a bacterial type nitrile
      hydratase enzyme but a nitrilase enzyme which can have a remarkably high nitrile
      hydratase activity.

PMID- 16786297
TI  - OsEIL1, a rice homolog of the Arabidopsis EIN3 regulates the ethylene response as
      a positive component.
AB  - The plant gaseous hormone ethylene regulates many aspects of plant growth,
      development and responses to the environment. ETHYLENE INSENSITIVE3 (EIN3) is a
      transcription factor involved in the ethylene signal transduction pathway in
      Arabidopsis. To gain a better understanding of the ethylene signal transduction
      pathway in rice, six EIN3-like genes (designated OsEIL1-6) were identified.
      OsEIL1, which showed highest similarity with EIN3, was isolated and functionally
      characterized. Ectopic expression of OsEIL1 in Arabidopsis can partially
      complement the ein3-1 mutant. The transgenic rice plants with overexpression of
      OsEIL1 exhibit short root, coiled primary root and slightly short shoot phenotype
      and elevated response to exogenous ethylene. OsEBP89, an ethylene responsive
      element binding protein (EREBP) and OsACO1, an ACC (1-aminocyclopropane-1
      carboxylic acid) oxidase gene were enhanced in the OsEIL1 overexpressing
      transgenic plants. These results indicate that OsEIL1 is involved in ethylene
      signal transduction pathway and acts as a positive regulator of ethylene response
      in rice.

PMID- 16786298
TI  - AtRLI2 is an endogenous suppressor of RNA silencing.
AB  - RNA silencing is a mechanism involved in gene regulation during development and
      anti-viral defense in plants and animals. Although many viral suppressors of this
      mechanism have been described up to now, this is not the case for endogenous
      suppressors. We have identified a novel endogenous suppressor in plants: RNase L
      inhibitor (RLI) of Arabidopsis thaliana. RLI is a very conserved protein among
      eukaryotes and archaea. It was first known as component of the interferon-induced
      mammalian 2'-5' oligoadenylate (2-5A) anti-viral pathway. This protein is in
      several organisms responsible for essential functions, which are not related to
      the 2-5A pathway, like ribosome biogenesis and translation initiation.
      Arabidopsis has two RLI paralogs. We have described in detail the expression
      pattern of one of these paralogs (AtRLI2), which is ubiquitously expressed in all
      plant organs during different developmental stages. Infiltrating Nicotiana
      benthamiana green fluorescent protein (GFP)-transgenic line with Agrobacterium
      strains harboring GFP and AtRLI2, we proved that AtRLI2 suppresses silencing at
      the local and at the systemic level, reducing drastically the amount of GFP small
      interfering RNAs.

PMID- 16786299
TI  - RNA interference of the Arabidopsis putative transcription factor TCP16 gene
      results in abortion of early pollen development.
AB  - Pollen development is a fundamental and essential biological process in seed
      plants. Pollen mother cells generated in anthers undergo meiosis, which gives
      rise to haploid microspores. The haploid cells then develop into mature pollen
      grains through two mitotic cell divisions. Although several sporophytic and
      gametophytic mutations affecting male gametogenesis have been identified and
      analyzed, little is known about the underlying molecular mechanism. In this
      study, we investigated the function of the TCP16 gene, which encodes a putative
      transcription factor. Expression analysis of the promoter::GUS fusion gene
      revealed that TCP16 transcription occurred predominantly in developing
      microspores. GUS expression began at the tetrad stage and markedly increased in
      an early unicellular stage. Transgenic plants harboring a TCP16 RNA interference
      (RNAi) construct generated equal amounts of normal and abnormal pollen grains.
      The abnormal pollen grains exhibited morphological abnormality and degeneration
      of genomic DNA. The defective phenotype of the RNAi plants was first detectable
      at the middle of the unicellular stage. Our results therefore suggest that TCP16,
      a putative transcription factor, plays a crucial role in early processes in
      pollen development.

PMID- 16786300
TI  - Uncovering the post-embryonic role of embryo essential genes in Arabidopsis using
      the controlled induction of visibly marked genetic mosaics: EMB506, an
      illustration.
AB  - The embryo essential gene EMB506 plays a crucial role in the transition of the
      Arabidopsis embryo from radial symmetry to bilateral symmetry just prior to the
      early heart stage of development. In addition to influencing embryo development
      EMB506 also affects chloroplast biogenesis. To further investigate the role of
      EMB506 gene expression in Arabidopsis we have generated green fluorescent protein
      (GFP) marked emb506 mosaic sectors at temporally defined stages during
      embryogenesis and additionally during various stages of vegetative growth, in
      otherwise phenotypically wild-type plants. We confirm the essential requirement
      for EMB506 gene expression in chloroplast biogenesis as reflected by the
      decreased chlorophyll content in emb506 mosaic sectors. We also show that the
      influence of EMB506 gene expression as it impinges on chloroplast biogenesis is
      first relevant at an intermediate stage in embryogenesis and that the role of
      EMB506 gene expression in chloroplast biogenesis is distinct from the essential
      role of EMB506 gene expression during early embryo development. By inducing
      emb506 mosaicism after the essential requirement for EMB506 gene expression in
      embryogenesis and also during vegetative growth we reveal that EMB506 gene
      expression additionally is required for correct cotyledon-, true leaf- and
      cauline leaf margin development. The strategy that we describe can be tailored to
      the mosaic analysis of any cloned EMB gene for which a corresponding mutant
      exists and can be applied to the mosaic analysis of mutant lethal genes in
      general.

PMID- 16786301
TI  - Overexpression of farnesyl diphosphate synthase in Arabidopsis mitochondria
      triggers light-dependent lesion formation and alters cytokinin homeostasis.
AB  - To investigate the role of mitochondrial farnesyl diphosphate synthase (FPS) in
      plant isoprenoid biosynthesis we characterized transgenic Arabidopsis thaliana
      plants overexpressing FPS1L isoform. This overexpressed protein was properly
      targeted to mitochondria yielding a mature and active form of the enzyme of 40
      kDa. Leaves from transgenic plants grown under continuous light exhibited
      symptoms of chlorosis and cell death correlating to H(2)O(2) accumulation, and
      leaves detached from the same plants displayed accelerated senescence.
      Overexpression of FPS in mitochondria also led to altered leaf cytokinin profile,
      with a reduction in the contents of physiologically active trans-zeatin- and
      isopentenyladenine-type cytokinins and their corresponding riboside
      monophosphates as well as enhanced levels of cis-zeatin 7-glucoside and storage
      cytokinin O-glucosides. Overexpression of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase did not prevent chlorosis in plants overexpressing FPS1L, but did
      rescue accelerated senescence of detached leaves and restored wild-type levels of
      cytokinins. We propose that the overexpression of FPS1L leads to an enhanced
      uptake and metabolism of mevalonic acid-derived isopentenyl diphosphate and/or
      dimethylallyl diphosphate by mitochondria, thereby altering cytokinin homeostasis
      and causing a mitochondrial dysfunction that renders plants more sensitive to the
      oxidative stress induced by continuous light.

PMID- 16786303
TI  - Characterization of T-DNA insertion mutants and RNAi silenced plants of
      Arabidopsis thaliana UV-damaged DNA binding protein 2 (AtUV-DDB2).
AB  - The human UV-damaged DNA binding protein (UV-DDB), a heterodimeric protein
      composed of 127 kDa (UV-DDB1) and 48 kDa (UV-DDB2) subunits, has been shown to be
      involved in DNA repair. To elucidate the in vivo function of plant UV-DDB2, we
      have analyzed T-DNA insertion mutants of the Arabidopsis thaliana UV-DDB2 subunit
      (atuv-ddb2 mutants) and AtUV-DDB2 RNAi silenced plants (atuv-ddb2 silenced
      plants). atuv-ddb2 mutants and atuv-ddb2 silenced plants were both viable,
      suggesting that AtUV-DDB2 is not essential for survival. Interestingly, both
      plant types showed a dwarf phenotype, implying impaired growth of the meristem.
      To the best of our knowledge, this is the first occasion that a dwarf phenotype
      has been found to be associated with a UV-DDB2 mutation in either plants or
      animals. The mutants also demonstrated increased sensitivity to UV irradiation,
      methyl methanesulfonate and hydrogen peroxide treatment, indicating that AtUV
      DDB2 is also involved in DNA repair. Our results lead us to suggest that not only
      does AtUV-DDB2 function in DNA repair, it also has a direct or indirect influence
      on cell proliferation in the plant meristem.

PMID- 16786302
TI  - Auxin flow in anther filaments is critical for pollen grain development through
      regulating pollen mitosis.
AB  - It was well known that auxin is critical for anther/pollen grain development,
      however, the clear distribution and detailed effects of auxin during floral
      development are still unclear. We have shown here that, through analyzing GUS
      activities of Arabidopsis lines harboring auxin response elements DR5-GUS, auxin
      was mainly accumulated in the anther during flower stages 10-12. Further studies
      employing the indoleacetic acid-lysine synthetase (iaaL) coding gene from
      Pseudomonas syringae subsp. savastanoi under control of the promoter region of
      Arabidopsis phosphatidylinositol monophosphate 5-kinase 1 gene, which conducts
      the anther filament-specific expression, showed that block of auxin flow of
      filaments resulted in shortened filaments and significantly defective pollen
      grains. Similar phenotype was observed in tobacco plants transformed with the
      same construct, confirming the effects of auxin flow in filaments on anther
      development. Detailed studies further revealed that the meiosis process of pollen
      grain was normal while the mitosis at later stage was significantly defected,
      indicating the effects of auxin flow in filaments on pollen grain mitosis
      process. Analysis employing [(14)C]IAA, as well as the observation on the
      expression of AtPIN1, coding for auxin efflux carrier, demonstrated the presence
      of polar auxin transport in anther filaments and pollen grains.

PMID- 16786304
TI  - Arabidopsis thaliana UBC13: implication of error-free DNA damage tolerance and
      Lys63-linked polyubiquitylation in plants.
AB  - Ubiquitylation is an important biochemical reaction found in all eukaryotic
      organisms and is involved in a wide range of cellular processes. Conventional
      ubiquitylation requires the formation of polyubiquitin chains linked through
      Lys48 of the ubiquitin, which targets specific proteins for degradation. Recently
      polyubiquitylation through a noncanonical Lys63 chain has been reported, and is
      required for error-free DNA damage tolerance (or postreplication repair) in
      yeast. To date, Ubc13 is the only known ubiquitin-conjugating enzyme (Ubc)
      capable of catalyzing the Lys63-linked polyubiquitylation reaction and this
      function requires interaction with the Ubc variant Mms2. No information is
      available on either Lys63-linked ubiquitylation or error-free damage tolerance in
      plants. We thus cloned and functionally characterized two Arabidopsis thaliana
      UBC13 genes, AtUBC13A and AtUBC13B. The two genes are highly conserved with
      respect to chromosomal structure and protein sequence, suggesting that they are
      derived from a recent gene duplication event. Both AtUbc13 proteins are able to
      physically interact with yeast or human Mms2, implying that plants also employ
      the Lys63-linked polyubiquitylation reaction. Furthermore, AtUBC13 genes are able
      to functionally complement the yeast ubc13 null mutant for spontaneous
      mutagenesis and sensitivity to DNA damaging agents, suggesting the existence of
      an error-free DNA damage tolerance pathway in plants. The AtUBC13 genes appear to
      express ubiquitously and are not induced by various conditions tested.

PMID- 16786305
TI  - Regulatory role of cystathionine-gamma-synthase and de novo synthesis of
      methionine in ethylene production during tomato fruit ripening.
AB  - The essential amino acid methionine is a substrate for the synthesis of S
      adenosyl-methionine (SAM), that donates its methyl group to numerous methylation
      reactions, and from which polyamines and ethylene are generated. To study the
      regulatory role of methionine synthesis in tomato fruit ripening, which requires
      a sharp increase in ethylene production, we cloned a cDNA encoding cystathionine
      gamma-synthase (CGS) from tomato and analysed its mRNA and protein levels during
      tomato fruit ripening. CGS mRNA and protein levels peaked at the "turning" stage
      and declined as the fruit ripened. Notably, the tomato CGS mRNA level in both
      leaves and fruit was negatively affected by methionine feeding, a regulation that
      Arabidopsis, but not potato CGS mRNA is subject to. A positive correlation was
      found between elevated ethylene production and increased CGS mRNA levels during
      the ethylene burst of the climacteric ripening of tomato fruit. In addition,
      wounding of pericarp from tomato fruit at the mature green stage stimulated both
      ethylene production and CGS mRNA level. Application of exogenous methionine to
      pericarp of mature green fruit increased ethylene evolution, suggesting that
      soluble methionine may be a rate limiting metabolite for ethylene synthesis.
      Moreover, treatment of mature green tomato fruit with the ethylene-releasing
      reagent Ethephon caused an induction of CGS mRNA level, indicating that CGS gene
      expression is regulated by ethylene. Taken together, these results imply that in
      addition to recycling of the methionine moieties via the Yang pathway, operating
      during synthesis of ethylene, de novo synthesis of methionine may be required
      when high rates of ethylene production are induced.

PMID- 16786306
TI  - Towards positional cloning in Brassica napus: generation and analysis of doubled
      haploid B. rapa possessing the B. napus pol CMS and Rfp nuclear restorer gene.
AB  - The Polima (pol) system of cytoplasmic male sterility (CMS) and its fertility
      restorer gene Rfp are used in hybrid rapeseed production in Brassica napus. To
      facilitate map-based cloning of the Rfp gene, we have successfully transferred
      the pol cytoplasm and Rfp from the amphidiploid B. napus to the diploid species
      B. rapa and generated a doubled haploid pol cytoplasm B. rapa population that
      segregates for the Rfp gene. This was achieved through interspecific crosses, in
      vitro rescue of hybrid embryos, backcrosses, and microspore culture. Male
      fertility conditioned by Rfp was shown to co-segregate in this population with
      Rfp-specific mitochondrial transcript modifications and with DNA markers
      previously shown to be linked to Rfp in B. napus. The selfed-progeny of one
      doubled haploid plant were confirmed to be characteristic B. rapa diploids by
      cytogenetic analysis. Clones recovered from a genomic library derived from this
      plant line using the RFLP probe cRF1 fell into several distinct physical contigs,
      one of which contained Rfp-linked polymorphic restriction fragments detected by
      this probe. This indicates that chromosomal DNA segments anchored in the Rfp
      region can be recovered from this library and that the library may therefore
      prove to be a useful resource for the eventual isolation of the Rfp gene.

PMID- 16786307
TI  - KIDARI, encoding a non-DNA Binding bHLH protein, represses light signal
      transduction in Arabidopsis thaliana.
AB  - Through activation tagging mutagenesis, we isolated a kidari-D (kdr-D) mutant,
      which exhibited a defect in blue and far-red light mediated photomorphogenesis.
      Under continuous blue light, the kdr-D mutant showed long hypocotyl phenotype,
      whereas it showed normal cotyledon opening and expansion. In addition, the kdr-D
      showed slightly longer hypocotyl under continuous far-red light, suggesting that
      KDR functions in a branch of cry signaling and mediates a cross-talk between cry
      and phyA. In the kdr-D mutant, a gene encoding a putative basic/Helix-Loop-Helix
      (bHLH) protein was overexpressed by the insertion of 35S enhancer into 10 kb
      upstream of the gene. Consistently, overexpression of this gene recapitulated the
      phenotype of kdr-D. KDR is composed of 94 amino acids with non-DNA binding HLH
      domain, a structure found in human Inhibitor of DNA binding 1 (Id-1) which
      functions as a negative regulator of bHLH proteins through heterodimerization
      with them. The KDR specifically interacted with HFR1, a bHLH protein regulating
      photomorphogenesis, in yeast two hybrid assay and the kdr-D was epistatic to
      35S::HFR1 in the hypocotyl phenotype. Thus, it shows that KDR functions as a
      negative regulator of HFR1, similar to Id-1 in human. The KDR exhibited circadian
      expression pattern with an increase during the day. Taken together, our results
      suggest that KDR attenuates light mediated responses in day light condition
      through inhibition of the activity of bHLH proteins involved in light signaling.

PMID- 16786308
TI  - Identification and characterization of a host reversibly glycosylated peptide
      that interacts with the Tomato leaf curl virus V1 protein.
AB  - Monopartite geminiviruses of the genus Begomovirus have two virion-sense genes,
      V1 and V2. V2 encodes the viral coat protein, but the function of V1 is largely
      unknown, although some studies suggest that it may play a role in cell-to-cell
      movement. Yeast two-hybrid technology was used to identify possible host binding
      partners of V1 from Tomato leaf curl virus (TLCV) to better understand its
      function. A protein closely related to a family of plant reversibly glycosylated
      peptides, designated SlUPTG1, was found to interact with V1 in yeast and in
      vitro. SlUPTG1 may function endogenously in the synthesis of cell wall
      polysaccharides, since a bacterially expressed form of the protein acted as an
      autocatalytic glycosyltransferase in vitro, a SlUPTG1:GFP fusion protein
      localized to the cell wall, and expression of SlUPTG1 appeared to be highest in
      actively dividing tissues. However, expression of SlUPTG1 in a transient TLCV
      replication assay increased the accumulation of viral DNA, suggesting that this
      host factor also plays a role in viral infection. Together, these data provide
      new insight into the role of V1 in TLCV infection and reveal another host pathway
      which geminiviruses may manipulate to achieve an efficient infection.

PMID- 16786309
TI  - Cell cycle regulated D3-type cyclins form active complexes with plant-specific B
      type cyclin-dependent kinase in vitro.
AB  - Tobacco (Nicotiana tabacum L.) cv Bright Yellow-2 (BY-2) cells are the most
      highly synchronizable plant cell culture, and previously we used them to analyze
      cell cycle regulation of cyclin-dependent kinases (CDKs) containing the cyclin
      binding motifs PSTAIRE (CDKA) and PPTA/TLRE (CDKB). Here we describe the analysis
      of tobacco CycD3 cyclins whose transcripts predominantly accumulate during G2 to
      M phase, which represents a unique feature of this type of cyclin D in plants.
      Although protein levels of CycD3s fluctuate with different patterns during the
      cell cycle, kinase assays revealed that the CycD3-associated kinases
      phosphorylate histone H1 and the tobacco retinoblastoma related protein (NtRBR1)
      with two peaks at the G1/S and G2/M boundaries. In vitro pull-down assays
      revealed that cell cycle-regulated CycD3s bind to CDKA, but more weakly than does
      CycD3;3, and that they also bind to CDKB and the CDK inhibitor NtKIS1a. Mutations
      in the cyclin box of the CycD3s showed that two amino acids are required for
      binding with CDKA and NtKIS1a, but no diminished interaction was observed with
      CDKB. A reconstituted kinase assay was adapted for use with bacterially produced
      GST-CycD3s, and kinase activity could be activated by incubation of extracts from
      exponentially growing BY-2 cells. Such activated complexes contained CDKA and
      CDKB, and the reconstituted GST-CycD3 mutants, retaining binding ability to CDKB,
      showed kinase activity, suggesting that these cell cycle-regulated CycD3s form
      active complexes with both A- and B-type CDKs in vitro.

PMID- 16786310
TI  - Subtractive cDNA libraries identify differentially expressed genes in dormant and
      growing buds of leafy spurge (Euphorbia esula).
AB  - Two subtractive cDNA libraries were developed to study genes associated with bud
      dormancy (reverse library) and initiation of shoot growth (forward library) in
      leafy spurge. To identify unique sequences represented in each library, 15744
      clones were screened to reduce the level of redundancy within both libraries. A
      total of 516 unique sequences were obtained from 2304 minimally redundant clones.
      Radioactive probes developed from RNAs extracted from crown buds of either intact
      (para-dormant control) or a series of growth-induced (2 h, 2, and 4 d after
      decapitation) plants were used to identify differentially expressed genes by
      macroarray analysis. Semi-quantitative RT-PCR was used to confirm results
      obtained by macroarray analysis and to determine the expression profiles for
      other transcripts identified within the subtractive libraries. Selected clones
      were also used to examine gene expression in crown buds after growth induction
      and/or during normal seasonal growth. In this study, four distinct patterns of
      gene expression were observed during the transition from para-dormancy to growth
      induction. Many of the differentially regulated genes identified have unknown or
      hypothetical functions while others are known to play important roles in
      molecular functions. Gene ontology analysis identified a greater proportion of
      genes involved with catalytic activity in the forward library while the reverse
      library had a greater proportion of genes involved in DNA/RNA binding.

PMID- 16786311
TI  - CENTRIN2 interacts with the Arabidopsis homolog of the human XPC protein (AtRAD4)
      and contributes to efficient synthesis-dependent repair of bulky DNA lesions.
AB  - Arabidopsis thaliana CENTRIN2 (AtCEN2) has been shown to modulate Nucleotide
      Excision Repair (NER) and Homologous Recombination (HR). The present study
      provides evidence that AtCEN2 interacts with the Arabidopsis homolog of human
      XPC, AtRAD4 and that the distal EF-hand Ca(2+) binding domain is essential for
      this interaction. In addition, the synthesis-dependent repair efficiency of bulky
      DNA lesions was enhanced in cell extracts prepared from Arabidopsis plants
      overexpressing the full length AtCEN2 but not in those overexpressing a truncated
      AtCEN2 form, suggesting a role for the distal EF-hand Ca(2+) binding domain in
      the early step of the NER process. Upon UV-C treatment the AtCEN2 protein was
      shown to be increased in concentration and to be localised in the nucleus
      rapidly. Taken together these data suggest that AtCEN2 is a part of the AtRAD4
      recognition complex and that this interaction is required for efficient NER. In
      addition, NER and HR appear to be differentially modulated upon exposure of
      plants to DNA damaging agents. This suggests in plants, that processing of bulky
      DNA lesions highly depends on the excision repair efficiency, especially the
      recognition step, thus influencing the recombinational repair pathway.

PMID- 16786312
TI  - Single-stranded DNA plant pathogens in Eilat.
AB  - An international conference on "Inter- and Intracellular Dynamics of ssDNA Plant
      Pathogens: Implications for Improving Resistance'' was sponsored by the United
      States-Israel Binational Agricultural Research and Development Fund (BARD) and
      organized in Eilat, Israel in November 2005. The topic of this meeting was single
      stranded plant pathogens, their inter- as well as intra-cellular dynamics and
      their implications for improving resistance. Most of the talks concentrated on
      new and very new findings on principles of virus and bacterium-host interactions,
      studies that no doubt will lead eventually to the establishment of plants
      resistant to viral and bacterial infections.

PMID- 16786313
TI  - Isolation of two populations of sperm cells from the pollen tube of Torenia
      fournieri.
AB  - The two sperm cells of Torenia fournieri are dimorphic. The dimorphic character
      suggests that they might be preferentially involved in fertilization during in
      vivo fusion with the egg cell and central cell. To probe the mechanism of
      preferential fertilization, it is necessary to use the most current molecular
      techniques. For this purpose, populations of >1000 individuals of the two
      dimorphic sperm cells, Sua (unassociated with the vegetative nucleus) and Svn
      (associated with the vegetative nucleus) were isolated from pollen tubes that had
      grown out of the cut ends of the styles. The two sperm cells released from pollen
      tubes remained attached to one another. When the two attached sperm cells were
      transferred into a solution containing 0.01% cellulose, 0.01% pectinase, and 5%
      mannitol, the connection between the two cells disappeared, and they were easily
      separated using a micromanipulator. The collection of these two individual
      populations containing over a thousand cells will permit research on gametic
      recognition at the molecular level.

PMID- 16786315
TI  - Antiperistaltic ileal segment in ileoanal "J" pouch surgery. Functional results
      could be improved?

PMID- 16786314
TI  - Expression of ipt gene controlled by an ethylene and auxin responsive fragment of
      the LEACO1 promoter increases flower number in transgenic Nicotiana tabacum.
AB  - Cytokinins play important roles in regulating plant growth and development. A new
      genetic construct for regulating cytokinin content in plant cells was cloned and
      tested. The gene coding for isopentenyl transferase (ipt) was placed under the
      control of a 0.821 kb fragment of the 1-aminocyclopropane-1-carboxylic acid (ACC)
      oxidase gene promoter from Lycopersicon esculentum (LEACO1) and introduced into
      Nicotiana tabacum (cv. Havana). Some LEACO1(0.821) (kb)-ipt transgenic plant
      lines displayed normal shoot morphology but with a dramatic increase in the
      number of flower buds compared to nontransgenic plants. Other transgenic lines
      produced excessive lateral branch development but no change in flower bud number.
      Isolated leaves of transgenic tobacco plants showed a significantly prolonged
      retention of chlorophyll under dark incubation (25 degrees C for 20 days). Leaves
      of nontransformed plants senesced gradually under the same conditions.
      Experiments with LEACO1(0.821) (kb)-gus transgenic tobacco plants suggested auxin
      and ethylene involvement in induction of LEACO1(0.821) (kb) promoter activity.
      Multiple copies of nucleotide base sequences associated with either ethylene or
      auxin response elements were identified in the LEACO1(0.821) (kb) promoter
      fragment. The LEACO1(0.821) (kb)-ipt fusion gene appears to have potential
      utility for improving certain ornamental and agricultural crop species by
      increasing flower bud initiation and altering branching habit.

PMID- 16786316
TI  - Laparoscopic anterior resection and total mesorectal excision for rectal cancer:
      a prospective nonrandomized study.
AB  - BACKGROUND: The purpose of this study was to present our experience of
      laparoscopic total mesorectal resection, including ultralow resection and
      coloanal anastomosis. MATERIALS AND METHODS: Between 1993 and 2005, patients fit
      for general anesthesia, with resectable cancers, and with lower edge of tumor
      beyond 5 cm of the anal verge were subjected to laparoscopic anterior resection
      with sphincter preservation. Double stapling technique is used to establish bowel
      continuity. RESULTS: A total of 170 patients, 88 males and 82 females, were
      subjected to successful laparoscopic anterior resection, which included high
      anterior resection (n=90), low anterior resection (n=52), ultralow anterior
      resection (n=20), and coloanal anastomosis (n=8). The average age of patients was
      58.4 years (12-90 years). Mean operating time was 130 min and mean hospital stay
      was 7 days. The morbidity was 13.5% with nil mortality. With an average follow-up
      of 49 months (range 9 years to 3 months), 9 patients developed local recurrence
      and 45 patients developed distant metastasis. CONCLUSION: In selected cases,
      laparoscopic anterior resection is possible for all levels of rectal tumors,
      allowing sphincter preservation and maintaining oncological safety.

PMID- 16786317
TI  - Colorectal cancer in a population with endemic Schistosoma mansoni: is this an at
      risk population?
AB  - PURPOSE: Chronic infection with schistosomiasis has been clearly associated with
      the development of bladder cancer, and infestation is associated with a high
      incidence of colorectal cancer in endemic populations. Despite this association,
      the potential role of alterations in tumor suppressor genes colorectal cancers
      has never been evaluated in an endemically infected population. The aim of this
      paper was to compare histopathologic and genetic changes in schistosomal colitis
      associated colorectal cancer (SCC) with colorectal cancer in a group of patients
      from the same population not affected by the disease (NDCC). MATERIALS AND
      METHODS: Sixty patients were included in this study: SCC-40, NDCC-20. Data
      collected included age, sex, clinical presentation, presence of synchronous
      tumors, histopathology, and clinical stage. p53, DCC (deleted in colorectal
      cancer gene), and mismatch repair genes (MLH1 and MSH2) were studied using
      immunohistochemical staining. RESULTS: Patients with SCC were significantly
      younger than the NDCC group (34.52+/-11.22 years vs 50.73+/-12.75 years, p=0.02).
      Mucinous adenocarcinoma occurred significantly more frequently in SCC (35 vs 10%,
      p=0.02). SCC tumors were more frequently stage III or IV, and significantly more
      synchronous tumors were present in the affected group (SCC-8/40 vs NDCC-1/20,
      p=0.05). p53 staining was far more frequent in SCC (SCC-32/40 vs NDCC-8/20,
      p=0.006). DCC expression was similar in two groups. There were only four cases,
      three in SCC and one in NDCC, that showed microsatellite instability. CONCLUSION:
      The data suggest that schistosomal colitis is more commonly associated with
      earlier onset of multicentric colorectal cancer, high percentage of mucinous
      adenocarcinoma, and presents at an advanced stage. The identification of a higher
      incidence of altered p53 expression in the SCC group raises the possibility of an
      association between schistosomiasis and alterations in p53 activation as an
      inciting event in colorectal cancer development.

PMID- 16786318
TI  - Induction of a leaf specific geranylgeranyl pyrophosphate synthase and emission
      of (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene in tomato are dependent on
      both jasmonic acid and salicylic acid signaling pathways.
AB  - Two cDNAs encoding geranylgeranyl pyrophosphate (GGPP) synthases from tomato
      (Lycopersicon esculentum) have been cloned and functionally expressed in
      Escherichia coli. LeGGPS1 was predominantly expressed in leaf tissue and LeGGPS2
      in ripening fruit and flower tissue. LeGGPS1 expression was induced in leaves by
      spider mite (Tetranychus urticae)-feeding and mechanical wounding in wild type
      tomato but not in the jasmonic acid (JA)-response mutant def-1 and the salicylic
      acid (SA)-deficient transgenic NahG line. Furthermore, LeGGPS1 expression could
      be induced in leaves of wild type tomato plants by JA- or methyl salicylate
      (MeSA)-treatment. In contrast, expression of LeGGPS2 was not induced in leaves by
      spider mite-feeding, wounding, JA- or MeSA-treatment. We show that emission of
      the GGPP-derived volatile terpenoid (E,E)-4,8,12-trimethyltrideca-1,3,7,11
      tetraene (TMTT) correlates with expression of LeGGPS1. An exception was MeSA
      treatment, which resulted in induction of LeGGPS1 but not in emission of TMTT. We
      show that there is an additional layer of regulation, because geranyllinalool
      synthase, catalyzing the first dedicated step in TMTT biosynthesis, was induced
      by JA but not by MeSA.

PMID- 16786319
TI  - Monoclonal gammopathy of undetermined significance and Helicobacter pylori
      infection.

PMID- 16786320
TI  - 18F-fluorodeoxyglucose positron emission tomography in patients with recurrent
      ovarian cancer: in comparison with vascularity, Ki-67, p53, and histologic grade.
AB  - The aim of this study was to assess the correlation between 18F
      fluorodeoxyglucose positron emission tomography (FDG PET) positivity of tumor
      recurrence and vascularity, Ki-67, p53, and histologic grade in patients with
      ovarian cancer. Nineteen patients with recurrent ovarian cancer underwent FDG PET
      before second-look surgery. Archival paraffin-embedded tissue materials were used
      to assess histologic grade including architectural pattern, mitotic activity, and
      nuclear pleomorphism; intratumor microvessel density (MVD); Ki-67; and p53.
      Univariate analysis was used to evaluate the correlation between FDG PET
      positivity and each biomarker. Stepwise logistic regression analysis was used to
      determine the best parameter to explain FDG PET positivity. MVD revealed
      significant positive correlation with FDG PET positivity (p=0.0341). There was no
      significant correlation between FDG PET positivity and Ki-67 or p53 (p=0.4040,
      p=0.6027). Mitotic activity yielded statistically significant positive
      correlations with FDG PET positivity (p=0.0448) although histologic grade
      revealed no positive correlation (p=1). Stepwise logistic regression analysis
      revealed MVD to be the strongest parameter for FDG PET positivity (OR=0.696, 95%
      CI 0.487-0.993, p=0.0458). In conclusion, FDG PET positivity revealed positive
      correlation with MVD and mitotic activity. MVD was the strongest parameter in
      predicting positive tumor recurrence on FDG PET.

PMID- 16786321
TI  - Acute knee trauma: role of ultrasound.
AB  - The purpose of this study was to determine the diagnostic accuracy of high
      spatial resolution ultrasonography (US) in the detection of lipohemarthrosis of
      the knee and to evaluate this sign as criteria of intra-articular fracture. Forty
      eight patients with clinical suspicion of knee fracture were prospectively
      examined by conventional radiography, sonography examination and computed
      tomography (CT) within 48 h after trauma in order to depict direct (fracture
      line) and indirect (lipohemarthrosis) signs of intra-articular fracture.
      Lipohemarthrosis was defined as a multi-layered collection in the
      subquadricipital recess. CT was considered as the gold standard for both direct
      and indirect fracture criteria. CT imaging showed direct signs of intra-articular
      fracture in 31 patients (65%). Among these patients, 30 (97%) had a
      lipohemarthrosis. Conventional radiographs showed intra-articular fracture in 26
      patients (54%). Among these, 18 (69%) had a lipohemarthrosis. Sonographic
      examinations could not depict any direct sign of intra-articular fracture but
      showed a lipohemarthrosis in 29 (93%) of patients with proven fracture via CT.
      This allowed the depiction of four out of five occult knee fractures. The
      sensitivity, specificity, positive predictive value, negative predictive value of
      sonography for the diagnosis of lipohemarthrosis was 97, 100, 100 and 94%,
      respectively, compared with 55, 100, 100 and 55% with conventional radiographs.
      Using lipohemarthrosis as criterion of fracture, the sensitivity, specificity,
      positive predictive value and negative predictive value of sonography for early
      detection of intra-articular knee fractures was 94, 94, 97 and 89%, respectively,
      compared with 84, 88, 93 and 75% with conventional radiographs. We concluded
      that, by showing lipohemarthrosis in the subquadricipital recess, high-resolution
      sonography is a reliable and accurate technique for the evaluation of intra
      articular knee fractures.

PMID- 16786322
TI  - Localization of thymosin beta10 in breast cancer cells: relationship to actin
      cytoskeletal remodeling and cell motility.
AB  - Beta-thymosins are polypeptides involved in the regulation of actin
      polymerization and thymosin beta10 and beta4 have been implicated in
      sequestration of monomeric (G-) actin. Additionally, experimental overexpression
      of thymosin beta10 has been found to result in increases in F-actin bundles as
      well as in cell motility and spreading. We have studied the distribution of
      endogenously expressed thymosin beta10 in cultured human breast cancer cell
      lines. Both unperturbed monolayer cultures and wound-healing models were examined
      using double-staining for thymosin beta10 and polymerized (F-) actin. Our
      findings show that thymosin beta10 is expressed in all three-cancer cell lines
      (SK-BR-3, MCF-7 and MDA-MB-231) studied. No or little staining was detected in
      confluent cells, whereas strong staining occurred in semiconfluent cells and in
      cells populating monolayer wounds. Importantly, the distribution of staining for
      thymosin beta10 was inverse of staining for F-actin. These data support a
      physiological role for thymosin beta10 in sequestration of G-actin as well as in
      cancer cell motility.

PMID- 16786323
TI  - Expression of SWAP-70 in the uterus and feto-maternal interface during embryonic
      implantation and pregnancy in the rhesus monkey (Macaca mulatta).
AB  - SWAP-70 is a unique signaling protein involved in multiple processes including
      lymphatic cell activation, migration, adhesion, and cytoskeleton organization.
      Its role in reproductive system remains to be unclear. In the present study, the
      spatial and temporal expression of SWAP-70 in the uterus during normal menstrual
      cycle as well as on the feto-maternal interface during pregnancy was investigated
      in the rhesus monkey by in situ hybridization and immunohistochemistry. It was
      shown that SWAP-70 was mainly expressed in glandular epithelial cells of uterine
      endometrium, and the level peaked at the mid-secretory stage. At the beginning of
      embryonic implantation, SWAP-70 was intensely expressed at the implantation site,
      mainly localized in glandular and luminal epithelial cells, as well as in primary
      trophoblasts and epithelial plaque. High level of SWAP-70 was observed in villous
      cytotrophoblast (VCT), syncytiotrophoblast (ST), column cytotrophoblast,
      trophoblast shell, interstitial trophoblast, and endovascular trophoblast during
      gestational days 15-25. From gestational day 50 to term, expression of SWAP-70
      decreased evidently and was restricted in VCT cells. What's more, SWAP-70 co
      localized with F-actin on the feto-maternal interface, especially in highly
      motive extravillous trophoblasts. The data indicate that SWAP-70 may be involved
      in regulating motility of trophoblast cells during embryonic implantation and
      placentation.

PMID- 16786324
TI  - Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and
      in extracellular mucous gel adherent to normal and damaged gastric mucosa.
AB  - Trefoil factor 2 (TFF2) is mucin associated peptide that has a mucosal barrier
      function in addition to participating in repair and healing. We examined the
      localization of TFF2 and gastric mucins in gastric mucous cells, the surface
      mucous gel layer (SMGL) adherent to normal gastric mucosa, and in the mucoid cap
      covering gastric erosions. Carnoy's solution, or formalin/picric acid-fixed
      paraffin embedded materials from resected stomachs and formalin-fixed paraffin
      embedded gastric biopsy materials were used. Sections were immunostained for the
      TFF2 and histochemically stained for gastric mucins. In addition, thick sectioned
      gastric mucosa fixed in Carnoy's solution were stained with FITC-labeled GSA-II
      lectin specific for gland mucous cell mucin and examined for three-dimensional
      images of the SMGL using a confocal laser scanning microscope. The TFF2 and gland
      mucous cell mucin were found intermixed together in the gastric gland mucous
      cells, in the SMGL in laminated layers, and in the mucoid cap. A laminated
      arrangement of continuous sheets of gland mucous cell mucin in the SMGL was
      demonstrated in the three-dimensional images. Co-localization of the TFF2 with
      gland mucous cell mucin suggests a physical interaction between the TFF2 and
      gland mucous cell mucin. The TFF2 trapped in the adherent mucins may be
      responsible for mucosal defense, healing, and repair.

PMID- 16786325
TI  - Plant phenological data and tree-rings as palaeoclimate indicators in south-west
      Finland since AD 1750.
AB  - Plant phenological data and tree-rings were tested for their palaeoclimatic value
      in south-west Finland since AD 1750. The information from fragmentary, partly
      overlapping, partly non-systematically biased plant phenological records of 14
      different phenomena (a total of 3,144 observations) was combined into one
      continuous time series of phenological indices. All site- and phenomenon-specific
      series were standardized to present an average of zero and standard deviation of
      one. The mean phenomenon-specific series were then averaged as arithmetic means
      for annually resolved time series representing the variability in the particular
      plant phenomenon. Consequently, each phenomenon-specific mean series was based on
      spatially normalized site-specific index series. These series were compared to
      each other, living-tree and subfossil tree-rings, and to early and modern
      meteorological time series. Phenological indices showed strong positive
      correlation with February to June temperatures. On the other hand, the
      correlations between phenological indices and precipitation data were around
      zero. Analysis using time-dependent running correlations showed non-stationary
      relationship between the tree-rings and phenological indices and observed spring
      temperatures. The skill of phenological data for reconstructing the spring
      temperatures was statistically proved.

PMID- 16786326
TI  - [Value of a combined ossification prophylaxis with indomethacin and radiotherapy
      for acetabular fractures].
AB  - BACKGROUND: Heterotopic ossification is a complication in patients with
      surgically treated acetabular fractures. The incidence is related to the surgical
      approach (extended iliofemoral, posterior or a combined approach). The objective
      of this study was to evaluate the incidence of heterotopic ossification in
      patients with acetabular fractures who received a combined prophylaxis with both
      a single dose of radiation and indomethacin compared to those who received only a
      prophylaxis with radiation or indomethacin. PATIENTS AND METHODS: A total of 24
      patients with a combined prophylaxis after surgery were examined retrospectively
      24 months after trauma. A systematic literature review was performed and our own
      results were compared with different methods for prophylaxis of heterotopic
      ossification from the literature. RESULTS: Only one patient developed a
      heterotopic ossification. In accordance with the literature, combined prophylaxis
      showed the least incidence of ossification compared to the other methods.
      Differences in incidence frequencies were significant between the different
      prophylaxis methods. CONCLUSION: A combined prophylaxis for heterotopic
      ossification in surgically treated acetabular fractures seems to be a better
      alternative than a prophylaxis with radiation or indomethacin alone.

PMID- 16786327
TI  - [Clinical experience with bone morphogenetic protein 7 (BMP 7) in nonunions of
      long bones].
AB  - BACKGROUND: Nonunions of long bone fractures are considerable therapeutic and
      economic problems with increasing tendency. Basic surgical options are autogenous
      cancellous bone grafting, rod dynamization, reamed nailing, plate fixation with
      compression, and bone transport techniques. If these methods fail to work,
      alternative treatment options are needed. MATERIAL AND METHODS: Since May 2001
      treatment with recombinant human (rh) bone morphogenic protein 7 [BMP-7 or
      osteogenic protein 1 (OP-1)] in combination with a type one collagen carrier has
      gained interest. BMP 7 induces the formation of new bone by differentiation of
      stem cells, thereby initiating the reaction cascade of osteogenesis. Nonunions
      over 9 months and unsuccessful bone grafting delineate the indication. RESULTS:
      We report our experience with 21 patients and nonunion of long bone fractures.
      Between July 2002 and June 2004, 23 units of BMP 7 were implanted. The
      implantation sites were 7 femora, 12 tibias, 2 humeri, and 2 forearms. In ten
      cases BMP 7 was combined with a new osteosynthesis and bone grafting and in five
      patients with bone grafting alone. In contrast in eight patients BMP 7 was
      applied as a single procedure without any bone grafting or any change of the
      osteosynthesis. CONCLUSION: There were no peri- or postoperative complications.
      Follow-up was obtained for a minimum of 6 months. Of 23 implantations, 22 were
      successful with bony healing revealed by clinical and radiological evaluation. In
      one patient no bony consolidation of the nonunion has been seen so far. In
      summary, based on our results we propose BMP 7 as an additional innovative
      therapy of long bone nonunions.

PMID- 16786328
TI  - Immunohistochemical localization of vascular endothelial growth factor and its
      receptor Flk-1 in the amphibian developing principal and accessory olfactory
      system.
AB  - In the last years several studies have shown that vascular endothelial growth
      factor (VEGF) is present in neural stem cells and mature neurons from different
      neural tissues where it may play an important role as a neuroproliferative and/or
      antiapoptotic factor. The olfactory neuroepithelium has the capability to replace
      dying neurons with new neurons formed by cell division from stem cells in the
      basal region of the epithelium. The present study demonstrates, for the first
      time, that VEGF is present in the olfactory epithelium, nerves and bulbs (both
      main and accessory) during the development of the toad Bufo arenarum. In this
      report, we detected VEGF immunoreactivity in mature olfactory neurons from early
      larval stages until the beginning of the metamorphic climax. VEGF expression
      decreases dramatically after metamorphosis. VEGF receptor Flk-1 was localized by
      immunohistochemistry, from premetamorphic larval stages until the climax in the
      neurons of the olfactory epithelium with a more intense labeling in the basal
      cell layer. Double-label immunofluorescence studies localized VEGF to the
      cytoplasm and the nucleus of mature neurons whereas Flk-1 was expressed in cell
      membranes. Flk-1 was present in neurons of both the main and accessory olfactory
      bulbs. After the end of metamorphosis, Flk-1 expression was limited to basal
      cells in the olfactory epithelium and Bowman's glands. The main and accessory
      olfactory bulbs showed the same pattern of Flk-1 immunostaining before and after
      the end of metamorphosis. The presence of VEGF and its receptor in the olfactory
      system suggests that VEGF may play an important role during neural development.

PMID- 16786329
TI  - Symptoms and weight loss in patients with gastrointestinal and lung cancer at
      presentation.
AB  - INTRODUCTION: Weight loss is an independent prognostic factor for decreased
      survival in cancer patients. The effectiveness of treatment is impaired in
      patients with weight loss. The aetiology of this weight loss is complex and
      poorly characterised. Decreased calorie intake may be important. The reasons for
      decreased intake are unknown. AIMS AND METHODS: To determine in adult patients
      with cancer, who had not started chemotherapy or radiotherapy, the prevalence of
      symptoms which carry a risk to nutritional status and how these relate to weight
      loss, tumour burden and primary tumour site. New patients referred for treatment
      of any form of gastrointestinal (GI) cancer, non-small cell lung cancer or lung
      mesothelioma completed a validated questionnaire recording symptoms contributing
      to weight loss (Patient-generated Subjective Global Assessment--PG-SGA). In a
      subset of patients without metastatic disease, computed tomography scans were
      assessed to determine tumour burden. RESULTS: Between August and October 2004,
      122 patients with GI and 29 with lung cancers were recruited. There were 48% of
      GI and 28% of lung cancer patients who had lost weight. Sixty-two percent of the
      patients had one or more symptoms at presentation. The frequency of symptoms
      varied according to the site of disease. The most common symptom at all tumour
      sites was loss of appetite (38%). There was a weak but significant correlation
      between the number of symptoms and amount of weight loss (r=0.347). Patients
      reporting a reduced food intake had more symptoms than patients who had not lost
      weight. Tumour burden did not correlate with weight loss. CONCLUSION: The
      symptoms in cancer patients occur across different types of primary tumours, may
      affect food intake and have a part in causing weight loss. More information on
      the role of symptom management in improving nutritional status is needed.

PMID- 16786330
TI  - Soluble triggering receptor expressed on myeloid cells 1: a biomarker for
      bacterial meningitis.
AB  - OBJECTIVE: To evaluate whether soluble triggering receptor expressed on myeloid
      cells 1 (sTREM-1) in CSF can serve as a biomarker for the presence of bacterial
      meningitis and outcome in patients with this disease. DESIGN: Retrospective study
      of diagnostic accuracy. SETTING AND PATIENTS: 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. RESULTS: CSF sTREM-1 levels were higher in patients with
      bacterial meningitis (median 82 pg/ml, range 0-988) than in those with viral
      meningitis (0 pg/ml, 0-48) and controls (0 pg/ml, 0-36). The diagnostic accuracy
      of sTREM-1 in discriminating between patients with and without bacterial
      meningitis, expressed as the area under the receiver operating characteristic
      curve, was 0.82. At a cutoff level of 20 pg/ml the sensitivity was 0.73 and
      specificity 0.77. In patients with bacterial meningitis CSF sTREM-1 levels were
      associated with mortality (survivors, median 73 pg/ml, range 0-449 pg/ml;
      nonsurvivors, 15 pg/ml, 0-988). CONCLUSIONS: Measuring sTREM-1 in CSF may be a
      valuable new additional approach to accurately diagnose bacterial meningitis and
      identify patients at high risk for adverse outcome. Therefore a prospective study
      of sTREM-1 as a biomarker in bacterial meningitis is needed.

PMID- 16786331
TI  - Adrenal axis function does not appear to be associated with hemodynamic
      improvement in septic shock patients systematically receiving glucocorticoid
      therapy.
AB  - OBJECTIVE: There is mounting evidence showing the value of low-dose
      corticosteroids in patients with septic shock requiring vasopressor therapy. It
      remains unclear whether adrenal function tests should be carried out
      systematically to guide the decision on glucocorticoid therapy. METHODS: The
      retrospective study was conducted in 52 patients in three university hospital
      ICUs. We included consecutive patients with catecholamine-dependent septic shock
      who had not received ketoconazole, glucocorticoids, or etomidate in the 24 h
      before the ACTH test, and who had survived to day 3 after the shock onset. All
      patients had a 250-microg ACTH test before systematic glucocorticoid therapy was
      started. Various definitions of relative adrenal insufficiency were used (based
      on cortisol basal level and/or change in cortisol level after ACTH stimulation).
      We defined hemodynamic improvement as a 50% reduction in the vasoactive agent
      dose in the 3 days following the initiation of glucocorticoid treatment. The
      relationship between the hemodynamic improvement and the results of the adrenal
      function tests was analyzed. RESULTS: Hemodynamic improvement occurred in 29
      patients (55.8%). Baseline characteristics, sites of infection, types of micro
      organisms and antibiotic management did not differ between patients with and
      those without hemodynamic improvement. Relative adrenal insufficiency whatever
      the definition was not associated with hemodynamic improvement. CONCLUSION: In
      catecholamine-dependent septic shock patients managed with systematic
      glucocorticoid therapy the results of ACTH stimulation do not predict hemodynamic
      improvement.

PMID- 16786332
TI  - Chronic lithium chloride administration to rats elevates glucose metabolism in
      wide areas of brain, while potentiating negative effects on metabolism of
      dopamine D2-like receptor stimulation.
AB  - RATIONALE AND OBJECTIVES: The regional cerebral metabolic rate for glucose
      (rCMRglc) can be imaged in vivo as a marker of brain functional activity. The
      effects of chronic lithium administration on baseline values of rCMRglc and
      values in response to administration of dopamine D2-like receptor agonists have
      not been examined in humans or rats. Knowing these effects may elucidate and
      localize the therapeutic action of lithium in bipolar disorder. METHODS: In
      unanesthetized rats, we used the 2-deoxy-D-glucose (2-DG) technique to image the
      effects of a 6-week control diet or LiCl diet sufficient to produce a plasma
      lithium concentration therapeutically relevant to bipolar disorder, on rCMRglc at
      baseline and in response to the dopaminergic D2-like receptor agonist, quinpirole
      (1 mg/kg i.v.), or to i.v. saline. RESULTS: Baseline rCMRglc was significantly
      elevated in 30 of 81 brain regions examined, in LiCl diet compared with control
      diet rats. Affected were visual and auditory structures, frontal cortex,
      amygdala, hippocampus, nucleus accumbens, caudate-putamen, interpeduncular
      nucleus, and substantia nigra. Acute quinpirole significantly decreased rCMRglc
      in four areas of the caudate-putamen in control diet rats, and in these and 19
      additional brain areas in LiCl-fed rats. CONCLUSIONS: In unanesthetized rats,
      chronic lithium administration widely upregulates baseline rCMRglc and
      potentiates the negative effects on rCMRglc of D2-like receptor stimulation. The
      baseline elevation may relate to lithium's reported ability to increase auditory
      and visual evoked responses in humans, whereas lithium's potentiation of
      quinpirole's negative effects on rCMRglc may be related to its therapeutic
      efficacy in bipolar disorder.

PMID- 16786333
TI  - Phase I and pharmacokinetic study of S-1 administered for 14 days in a 21-day
      cycle in patients with advanced upper gastrointestinal cancer.
AB  - PURPOSE: S-1 is a novel oral fluoropyrimidine that combines tegafur with CDHP and
      oxonic acid. To decrease the incidence of late onset, severe diarrhea observed in
      a previous study, a phase I study was conducted to determine the maximum
      tolerated dose (MTD) of S-1 utilizing a 14-day schedule, repeated every 21 days,
      in patients with chemotherapy-refractory upper gastrointestinal malignancies.
      METHODS: S-1 was administered orally, twice-daily, at an initial dose level of 30
      mg/m2/dose; doses were escalated by 5 mg/m2 at each level. A minimum of three
      patients were enrolled at each dose level. S-1 toxicity, antitumor activity, and
      pharmacokinetics were assessed. The MTD was based on the dose limiting toxicity
      (DLT) during the first treatment cycle. RESULTS: At 30 mg/m2 no DLT was observed
      in the first three evaluable patients. Two of the first three patients at the 35
      mg/m2 dose level developed DLTs (grade 3 rash and dehydration). An additional
      nine patients were subsequently treated at 30 mg/m2 without DLT and this dose was
      established as the MTD. Common toxicities at 30 mg/m2 included diarrhea, nausea,
      skin rash, anorexia, and fatigue. No grade 4 toxicities were observed. One
      partial response was seen in a patient with gemcitabine-refractory pancreatic
      adenocarcinoma and ten patients with pancreatic, gastric, or gallbladder
      carcinomas achieved stable disease as their best response to therapy. The AUC(0
      8) of 5-FU at the 30 and 35 mg/m2 dose levels were 875 +/- 212 and 894 +/- 151 h
      ng/ml, respectively. CONCLUSIONS: In a 14-day dosing schedule, the MTD of S-1 was
      30 mg/m2 and preliminary evidence of antitumor activity was seen in a North
      American population with refractory upper gastrointestinal malignancies.

PMID- 16786334
TI  - Blood lipid profile and myocardial superoxide dismutase in swim-trained young and
      middle-aged rats: comparison between left and right ventricular adaptations to
      oxidative stress.
AB  - Region-wise interactive effects of age, swim intensity, and duration on exercise
      performance in the myocardium and serum lipid profile in young (4 months) and
      middle-aged (12 months) rats were examined. Animals were allocated to the
      sedentary control (SE-C) or one of the nine trainee groups. Swim training was for
      6 days/week and for 4 weeks at 3 durations (20, 40, and 60 min/day) and
      intensities (2%, low; 3%, medium; 5%, high). Swim velocity and external work
      showed an age-related decline with low-intensity of 20 min/day in the middle
      aged. Reduction in serum cholesterol, low-density lipoproteins (LDLs), and
      triglycerides were accompanied by elevated levels in high-density lipoprotein in
      the low-to-moderately trained ones for 20 and 40 min/day. Training at 2%,
      intensity for 20 min/day was sufficient to alter the blood lipid profile and
      improve swim performance, and endurance in terms of blood lactate. A concomitant
      increase in Mn-superoxide dismutase (Mn-SOD) activity and reduced malondialdehyde
      in the left ventricle (LV) and right ventricle (RV) were evident. Lipofuscin was
      higher in the LV compared to RV. Our results reflect the minimization of free
      radical generation through appropriate exercise protocols. Our findings on
      improved blood lipid profile could be related to lower free radicals, which would
      otherwise oxidize LDLs. Further, swim training when initiated in the young and
      middle age for as low as 20 min/day at 2% intensity improves the Mn-SOD in the LV
      and RV. However, the adaptive response of the LV was weaker when compared to the
      RV, more so in the middle aged.

PMID- 16786335
TI  - Seasonal regulations of energetics, serum concentrations of leptin, and
      uncoupling protein 1 content of brown adipose tissue in root voles (Microtus
      oeconomus) from the Qinghai-Tibetan plateau.
AB  - Survival of small mammals in winter requires proper adjustments in physiology,
      behavior and morphology. The present study was designed to examine the changes in
      serum leptin concentration and the molecular basis of thermogenesis in seasonally
      acclimatized root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau. In
      January root voles had lower body mass and body fat mass coupled with higher
      nonshivering thermogenesis (NST) capacity. Consistently, cytochrome c oxidase
      activity and mitochondrial uncoupling protein-1 (UCP1) protein contents in brown
      adipose tissues were higher in January as compared to that in July. Circulating
      level of serum leptin was significantly lower in winter and higher in July.
      Correlation analysis showed that serum leptin levels were positively related with
      body mass and body fat mass while negatively correlated with UCP1 protein
      contents. Together, these data provided further evidence for our previous
      findings that root voles from the Qinghai-Tibetan plateau mainly depend on higher
      NST coupled with lower body mass to enhance winter survival. Further, fat
      deposition was significantly mobilized in cold winter and leptin was potentially
      involved in the regulation of body mass and thermogenesis in root voles. Serum
      leptin might act as a starvation signal in winter and satiety signal in summer.

PMID- 16786336
TI  - Natural history of bone bruises after acute knee injury: clinical outcome and
      histopathological findings.
AB  - The purpose of this paper is to review the scientific literature on the natural
      history of bone bruises and the experimental studies regarding the
      histopathological effects of impaction load on articular cartilage and
      subchondral bone. Bone bruises with subchondral or osteochondral injuries, or
      geographic bone bruises seemed to be persistent for years after trauma on MRI.
      Biopsy samples of the articular cartilage overlying the bone bruise lesions
      showed degeneration or necrosis of chondrocytes and loss of proteoglycan.
      Experimental studies using a single impact load revealed chondrocytes death,
      alteration of the mechanical properties of cartilage explants and/or an increase
      in the thickness of subchondral bone. These data are indicative of a significant
      injury to normal articular cartilage homeostasis, and support the suggestion that
      severe bone bruise is a precursor of early degenerative changes. We recommend
      delaying return to full weightbearing status when a severe bone bruise is
      detected to prevent further collapse of subchondral bone and further aggravation
      of articular cartilage injury.

PMID- 16786337
TI  - CT changes after trochleoplasty for symptomatic trochlear dysplasia.
AB  - Trochlear dysplasia is an important risk factor for patellar instability. Because
      of a decreased trochlear depth in combination with a low lateral femoral condyle,
      the patella cannot engage properly in the trochlea. Trochleoplasty is a surgical
      procedure, which strives to correct such bony abnormalities. The aim of this
      study was to describe morphological features of trochlear dysplasia and the
      corrective changes after trochleoplasty on CT scan. The study group consists of
      17 knees with trochlear dysplasia having undergone trochleoplasty for recurrent
      patellofemoral dislocation at a mean age of 22.4 years. The evaluation consisted
      in pre- and postoperative measurements on the proximal and distal trochlea on
      transverse CT scans in order to determine the morphological features. We measured
      the transverse position and depth of the trochlear groove, the transverse
      position of the patella, the ratio between the posterior patellar edge and the
      trochlear groove, the lateral patellar inclination angle, the sulcus angle, and
      the lateral trochlear slope. The trochlear groove lateralised a mean of 6.1 mm in
      the proximal aspect and 2.5 mm in the distal aspect of the trochlea, while the
      patella medialised a mean of 5 mm. Preoperatively the patella was lateral in
      relation to the trochlear groove in 13 cases, neutral in two cases, and medial in
      two cases. Postoperatively it was lateral in four cases, in neutral position in
      seven cases, and medialised in six cases, referenced to the trochlear groove. The
      trochlear depth increased from 0 to 5.9 mm postoperatively in the proximal aspect
      of the trochlea, and from 5.5 to 8.3 mm postoperatively in the distal trochlea.
      The lateral patellar inclination angle decreased from a mean of 21.9 degrees to a
      mean of 7.8 degrees . The sulcus angle decreased from a mean of 172.1 degrees to
      a mean of 133 degrees in the proximal trochlea and from a mean of 141.9 degrees
      to a mean of 121.7 degrees in the distal trochlea. The lateral trochlear slope
      changed from 2.8 degrees to 22.7 degrees in the proximal and from 14.9 degrees to
      26.9 degrees in the distal part of the trochlea. In the CT scan patients with
      trochlear dysplasia demonstrated a poor depth, or even a flat or convex trochlea
      with a greater sulcus and lateral trochlear slope angle, a lateralised patella to
      the trochlear groove with poor congruency, and a greater lateral patellar
      inclination angle. Trochleoplasty can correct the pathological features of
      trochlear dysplasia by surgically creating more normal anatomy. The goal of this
      surgical procedure is to steepen and lateralise the trochlear groove for a better
      engagement of the patella.

PMID- 16786338
TI  - [Damage to large tendons: Achilles, patellar and quadriceps tendons].
AB  - The etiology and mechanisms of Achilles, patellar and quadriceps tendon ruptures
      are very similar. Age dependent changes in tendon structure and disorders such
      gout, diabetes, rheumatic diseases and chronic renal failure are associated
      causes. The main mechanism of rupture is indirect trauma. Although clinical
      diagnosis is easy, ruptures are still frequently missed. Sonography is the main
      standard diagnostic tool. MRI is indicated only in special cases. Open operative
      repair is the most common treatment for quadriceps and patellar tendon ruptures.
      Treatment of Achilles tendon ruptures is moving towards an individualized choice
      of therapy. Percutaneous and other "minimally invasive" techniques will play an
      increasingly important role.

PMID- 16786339
TI  - [Trends in surgical intensive care. Experience in one centre over 12 years].
AB  - BACKGROUND: For critically ill medical patients until the year 2000, increases in
      patient age and severity of disease but also acute prognosis have been described.
      Since then, further improvement appears possible. Several controlled studies have
      recently demonstrated that acute mortality may be further lowered by new adjuvant
      therapies such as aggressive glycemic control. However, it is still unknown
      whether demographic changes and progress in intensive care can be reproduced in
      surgical critically ill patients outside of a controlled trial setting. METHODS:
      We performed a retrospective, observational cohort study using data prospectively
      collected from the surgical intensive care unit (ICU) of the LMU Department of
      Surgery in Munich, Germany, Grosshadern Campus, from March 1 1993 through
      February 28 2005. Since 1999 we have successively introduced a variety of new
      therapies to daily routine. A cohort of 5,495 patients was analysed. RESULTS: We
      identified reduced ICU mortality during the observation period, although age rose
      simultaneously and disease severity remained constant. Results from multivariate
      analysis suggest that improvements in prognosis essentially result from the
      implementation of new therapies after 2001. After adjusting for more than 20
      covariables, treatment received after 2001 was identified as an independent
      factor linked with reduced risk of death. CONCLUSIONS: General demographic trends
      and progress in intensive care can be demonstrated also in unselected surgical
      cohorts. Furthermore, the results here confirm the efficacy of new therapeutic
      modifications in routine therapy.

PMID- 16786340
TI  - [Unclear soft-tissue tumor].
AB  - Cystic necrotization with liquefaction and calcification of muscle tissue is a
      rare late sequel of compartmental syndrome. Diagnosis and treatment of this
      clinical picture is still a problem. In the literature, various therapeutic
      approaches are described such as incision, needle decompression, and complete
      compartmental debridement. We report a case in which cystic degradation and
      liquefaction of three compartments developed 51 years after a complete fracture
      of the tibia. The patient was treated by radical compartmental resection. No
      postoperative complication was noted, and almost no functional loss occurred.

PMID- 16786341
TI  - [The new curriculum for surgery in Hamburg, Germany].
AB  - In October 2004, the medical faculty of Hamburg University started a program to
      restructure completely clinical teaching according to new state regulations of
      June 2002. In this new curriculum design, the surgical disciplines were
      horizontally and vertically interconnected and integrated, with a focus on
      practical training and problem-based teaching. This study describes the concept
      of clinical teaching and presents the student evaluation results of the first
      four blocks with a focus on performance in surgical disciplines. There was high
      student satisfaction with the new program, compared with results before October
      2004 and also with respect to other disciplines within the new curriculum. This
      was especially true for the practical courses in the newly established skills
      lab. Future developments in e-learning and practical teaching in the skills lab
      are necessary to overcome restrictions on medical education due to changes in the
      German health care system.

PMID- 16786343
TI  - Evaluation of leptin level and Ob gene polymorphism in patients with Behcet's
      disease.
AB  - The present study was aimed to evaluate serum leptin level and the frequency of
      oligopolymorphic codon 25 (CAA/CAG) of Ob gene in Behcet's disease. Eighty-seven
      patients with Behcet's disease and 85 healthy controls with matched age, gender
      and body mass index were included in the study. Serum leptin level was determined
      and genotype of codon 25 of Ob gene was performed by using the PCR amplification
      after DNA extraction. Serum leptin concentration of the patients with Behcet's
      disease (23.8 +/- 22.8 ng/ml) was higher than that of the control groups (17.1 +/
      14.7 ng/ml). The patients with Behcet's disease and control subjects showed
      CAA/CAA genotype, indicating the presence of no polymorphism. Neither Behcet's
      disease nor serum leptin level was found to be related to codon 25 polymorphism.
      We concluded that leptin 25CAG polymorphism is not associated with Behcet's
      disease and serum leptin level.

PMID- 16786342
TI  - Allelic configuration and polysomic inheritance of highly variable
      microsatellites in tetraploid gynodioecious Thymus praecox agg.
AB  - Polyploidy plays a pivotal role in plant evolution. However, polyploids with
      polysomic inheritance have hitherto been severely underrepresented in plant
      population genetic studies, mainly due to a lack of appropriate molecular genetic
      markers. Here we report the establishment and experimental validation of six
      fully informative microsatellite markers in tetraploid gynodioecious Thymus
      praecox agg. Sequence data of 150 microsatellite alleles and their flanking
      regions revealed high variation, which may be characteristic for polyploids with
      a reticulate evolutionary history. Understanding the patterns of mutation (indels
      and substitutions) in microsatellite flanking-sequences was a prerequisite for
      the development of co-dominant markers for fragment analyses. Allelic segregation
      patterns among progeny arrays from ten test crosses revealed tetrasomic
      inheritance in T. praecox agg. No evidence of frequent double reduction was
      detected. Polymerase chain reaction (PCR) based dosage effects allowed for
      precise assignment of allelic configuration at all six microsatellite loci. The
      quantification of allele copy numbers in PCR was verified by comparisons of
      observed and expected gametic allele frequencies and heterozygosities in test
      crosses. Our study illustrates how PCR based markers can provide reliable
      estimates of heterozygosity and, thus, powerful tools for breeding system and
      population genetic analyses in polyploid organisms.

PMID- 16786344
TI  - Induction of cellular immunity against hair follicle melanocyte causes alopecia.
AB  - Alopecia areata (AA) is generally regarded as an organ-specific autoimmune
      disease. Although it has been hypothesized that the autoimmunity is mediated by T
      cells and that hair follicle melanocyte is one of the targets, definitive
      evidence is lacking. We here demonstrate that AA-like lesions can be induced in
      mice by inducing CD8(+) T-cell-mediated immunity to hair follicle melanocytes. We
      found that hair loss was induced in mice-bearing interleukin-12-producing B16
      melanoma cells by the depletion of CD4(+) T cells, accompanied by vitiligo-like
      coat color change. The alopecic lesions varied in size from pachy to extensive.
      In many instances, hair loss developed and was followed by the regrowth of white
      hairs. Histological analysis revealed that mononuclear cells infiltrated in and
      around the bulb region of hair follicles. Furthermore, immunohistochemical
      examination clearly showed the intra-follicular infiltration of CD8(+) T cells.
      Neither the vitiligo-like coat color nor AA-like lesions were induced when CD8(+)
      T cells were codepleted. These observations indicate that the induction of CD8(+)
      T-cell-mediated immunity against hair follicle melanocytes causes alopecia. It is
      thought that there are many types of AA with different mechanisms, targets etc.
      Although hair follicle melanocytes have long been thought to be one of the
      targets of AA, evidence to support the hypothesis is sparse. Therefore, we
      believe that our observation is significant to support the hypothesis.

PMID- 16786345
TI  - Comparison of sebum secretion, skin type, pH in humans with and without acne.
AB  - Differences of skin type and pH between subjects with and without acne have not
      been investigated. In addition, the relationship between sebum secretion and pH
      in these populations has not been determined. This study assessed the differences
      in objective and subjective skin types between these two groups. Secondly, this
      study evaluated the difference in pH on five facial areas (forehead, nose, chin,
      right and left cheeks) between the two populations. Lastly, the relationship
      between pH and sebum secretion was analyzed in each population. Sebum casual
      levels (CL) of the five facial areas in 36 Koreans with acne and 47 Koreans
      without acne were measured by using a Sebumeter SM 815 and subjects were
      classified into objective skin types by CL. Subjects reported the type of skin
      they believed they had, which determined the subjective skin type. The pH levels
      of the five facial areas were measured by the Skin-pH-Meter PH 905. Data were
      assessed with adequate statistical tests depending on data type and distribution.
      Among the five areas, the nose of the subjects with acne showed a significantly
      higher CL, compared to the subjects without acne. This difference in CL on the
      nose resulted in the difference in CL on the T-zone and mean facial sebum
      excretions (MFSE). Although CL differed, objective skin types did not differ
      between the two groups (P > 0.05), but the subjective skin types differed
      significantly (P = 0.001). In addition, the objective skin types were
      significantly different than the subjective skin types in subjects with acne (P =
      0.001), whereas the two skin types did not differ in subjects without acne.
      Subjects with acne actually overestimated their skin types and stated their skin
      types were "oilier" than they were. In respect to pH, none of the five areas
      differed significantly between the two groups. Among the five sites in subjects
      with acne, CL showed a significant negative correlation with pH on the left (r (2
      )=0.12) and right (r ( 2 )=0.15) cheeks, which resulted in a significant negative
      correlation on the U-zone (r ( 2 )=0.14). In contrast, in subjects without acne,
      there was a significant negative correlation between CL and pH on the forehead (r
      ( 2 )=0.10) and chin (r ( 2 )=0.16), which led to a significant negative
      correlation on the T-zone (r ( 2 )=0.14).

PMID- 16786346
TI  - Unfolding time distribution of GFP by single molecule fluorescence spectroscopy.
AB  - We have studied the unfolding of single molecules of GFP-mut2 mutant trapped in
      wet silica gels in a wide range of GuHCl concentration. After the addition of
      denaturant, the number of fluorescent molecules decreases with unfolding rates
      (of the order of 0.01 min(-1)) that are in very good agreement with bulk
      fluorescence and circular dichroism data. Unexpectedly, single molecule
      experiments show rare fluctuations in the number of fluorescent proteins at
      equilibrium. On the other hand, although a first approximate description of the
      number decays can be reasonably performed by single exponential functions, the
      distributions of the single molecule unfolding times show a maximum at times
      congruent with 50-100 min up to the denaturation midpoint concentration of
      [GuHCl] congruent with 2.5 M. A theoretical analysis of the distributions
      indicates that this feature is a fingerprint of the competition between unfolding
      and refolding processes when the protein is very far from the midpoint denaturant
      concentration.

PMID- 16786347
TI  - Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours
      for 13 weeks.
AB  - Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm)
      and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by
      inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological
      investigation 8 weeks after the end of exposure. Brainstem auditory-evoked
      responses were used to determine auditory thresholds at different frequencies.
      Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four
      concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz
      in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses
      of outer hair cells of the organ of Corti occurred in animals exposed to the four
      concentrations studied. Exposure to both mixed xylenes produced ototoxicity
      characterized by increased auditory thresholds and losses of outer hair cells.
      Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the
      mixed xylene studied and the area of the concentration-response curves taken into
      account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a
      given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given
      the high ototoxicity of ethylbenzene, the safety margin of less or equal to two
      (LOAEL/TWA) might be too small to protect workers from the potential risk of
      ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene
      observed in mixed xylenes should encourage the production of mixed xylenes with
      the lowest possible concentrations of ethylbenzene and para-xylene.

PMID- 16786348
TI  - The contribution of diffusion-weighted MR imaging to distinguishing typical from
      atypical meningiomas.
AB  - INTRODUCTION: Atypical/malignant meningiomas recur more frequently then typical
      meningiomas. In this study, the contribution of diffusion-weighted MR imaging to
      the differentiation of atypical/malignant and typical meningiomas and to the
      determination of histological subtypes of typical meningiomas was investigated.
      METHODS: The study was performed prospectively on 39 patients. The signal
      intensity of the lesions was evaluated on trace and apparent diffusion
      coefficient (ADC) images. ADC values were measured in the lesions and peritumoral
      edema. Student's t-test was used for statistical analysis. P<0.05 was considered
      statistically significant. RESULTS: Mean ADC values in atypical/malignant and
      typical meningiomas were 0.75+/-0.21 and 1.17+/-0.21, respectively. Mean ADC
      values for subtypes of typical meningiomas were as follows: meningothelial,
      1.09+/-0.20; transitional, 1.19+/-0.07; fibroblastic, 1.29+/-0.28; and
      angiomatous, 1.48+/-0.10. Normal white matter was 0.91+/-0.10. ADC values of
      typical meningiomas and atypical/malignant meningiomas significantly differed
      (P<0.001). However, the difference between peritumoral edema ADC values was not
      significant (P>0.05). Furthermore, the difference between the subtypes of typical
      meningiomas and atypical/malignant meningiomas was significant (P<0.001).
      CONCLUSION: Diffusion-weighted MR imaging findings of atypical/malignant
      meningiomas and typical meningiomas differ. Atypical/malignant meningiomas have
      lower intratumoral ADC values than typical meningiomas. Mean ADC values for
      peritumoral edema do not differ between typical and atypical meningiomas.

PMID- 16786350
TI  - Anterior cerebral artery variations detected by MR angiography.
AB  - INTRODUCTION: From anatomical and angiographic studies, it is well known that
      there are several variations of the anterior cerebral artery (ACA). However, ACA
      variations have rarely been studied by magnetic resonance (MR) angiography. The
      purpose of this study was to investigate not only the type, location,
      configuration, and incidence of ACA variations, but also coexisting arterial
      pathology such as aneurysms detected by cranial MR angiography. METHODS: We
      retrospectively reviewed cranial MR angiography images of 891 patients at our
      institution. All images were obtained with one of two 1.5-T scanners using the
      three-dimensional time-of-flight technique. Maximum intensity projection (MIP)
      images in the horizontal rotation view were displayed stereoscopically. We
      reviewed these horizontal MIP images, inferosuperior MIP images, and source
      images, and identified variations of the ACA. RESULTS: We found 50 instances
      (5.6%) of unilateral A1 segment aplasia, 27 (3.0%) of three A2 segments, 18
      (2.0%) of an unpaired A2 segment, and 11 (1.2%) fenestrations of the A1 and/or A2
      segment. Seven anterior communicating artery (ACoA) aneurysms and one ACA
      territory embolic infarction were found among the 50 patients with unilateral A1
      segment aplasia. One ACoA aneurysm and one pericallosal infarction were found in
      the 27 patients with three A2 segments. Two distal ACA aneurysms were detected
      among the 18 patients with an unpaired A2 segment. No associated aneurysm was
      seen at the fenestrations. CONCLUSION: Although the clinical significance of ACA
      variations is usually minor, an associated aneurysm is found relatively
      frequently. Thus, recognizing ACA variations during the interpretation of cranial
      MR angiograms is important.

PMID- 16786349
TI  - Paediatric dissecting posterior cerebral aneurysms: report of two cases and
      review of the literature.
AB  - INTRODUCTION: Intracranial aneurysms in the paediatric population are uncommon,
      accounting for 2% to 6% of all aneurysms, and spontaneous arterial dissection is
      rarely reported as the cause of aneurysms in children, especially in the
      posterior cerebral artery. METHODS: Two cases of paediatric spontaneous posterior
      cerebral artery dissecting aneurysms are reported, one in a 33-month-old male
      child presenting with aneurysmal rupture and subarachnoid haemorrhage and the
      other in a 9-year-old boy with an unruptured aneurysm. RESULTS: The first child
      was successfully treated by endovascular parent vessel occlusion without
      neurological deficit and in the second a spontaneous thrombosis of the aneurysm
      and its parent artery occurred associated with hydrocephalus and a favourable
      outcome. CONCLUSION: Dissecting aneurysms are dynamic lesions with variable and
      unpredictable evolution and close follow-up and/or early treatment is warranted.
      Spontaneous arterial dissection is a rare, probably still under-recognized, cause
      of intracranial aneurysms that may be responsible for a significant number of
      aneurysms and spontaneous aneurysmal thromboses in children.

PMID- 16786351
TI  - Impaired cognitive functions in mild traumatic brain injury patients with normal
      and pathologic magnetic resonance imaging.
AB  - INTRODUCTION: Mild traumatic brain injury (MTBI) is a common neurological
      (neurotraumatological) diagnosis. As well as different subjective symptoms, many
      patients develop neuropsychological dysfunction with objective impairment of
      attention, memory and certain executive functions. Magnetic resonance imaging
      (MRI) is not routinely used in MTBI patients despite its proven greater
      sensitivity and specificity in comparison with computed tomography (CT). METHODS:
      The patient group consisted of 30 persons with MTBI and the control group
      consisted of 30 sex- and age-matched healthy volunteers. Both groups underwent
      neurological examination, neuropsychological testing (including the
      Postconcussion Symptoms Scale questionnaire, PCSS) and brain MRI (the patient
      group within 96 h after injury). RESULTS: The analyzed groups did not differ
      significantly in terms of sex, age, or level or duration of education. MRI
      pathological findings (traumatic and nonspecific) were present in nine patients.
      Traumatic lesions were found in seven patients. Nonspecific white matter lesions
      were found in five healthy controls. There were significant differences between
      MTBI patients and controls in terms of subjective symptoms (PCSS) and selected
      neuropsychological tests. Statistically significant neuropsychological
      differences were found between MTBI patients with true traumatic lesions and MTBI
      patients with nonspecific lesions. CONCLUSION: There is evidence that MTBI
      patients with true traumatic MRI lesions are neuropsychologically different from
      MTBI patients with nonspecific MRI lesions or normal brain MRI. These results
      support the hypothesis that some acute MTBI signs and symptoms have a real
      organic basis which can be detected by selected new MRI modalities.

PMID- 16786352
TI  - Exploring the mental number line: evidence from a dual-task paradigm.
AB  - In a parity-judgment task smaller numbers are responded to faster with the left
      hand key and vice versa for larger numbers (SNARC effect; Dehaene et al., in
      Journal of Experimental Psychology: General, 122, 371-396, 1993). We used the
      psychological refractory period paradigm involving a parity-judgment task and
      tone-discrimination task to address the question at which stage this effect
      arises. When the parity-judgment task is performed second, then we found equal
      SNARC effects for the short and the long SOA. According to the central bottleneck
      model, this indicates that the effect arises during the response-selection or
      execution stage. In Experiment 2 the parity-judgment task was performed first.
      The pattern of results indicates that the SNARC effect originates during the
      perceptual encoding or response-selection. Together, our results suggest that the
      SNARC effect originates while the response is selected.

PMID- 16786353
TI  - Multiple temporal references in sensorimotor synchronization with metrical
      auditory sequences.
AB  - A local phase perturbation in an auditory sequence during synchronized finger
      tapping elicits an automatic phase correction response (PCR). The stimulus for
      the PCR is usually considered to be the most recent tap-tone asynchrony. In this
      study, participants tapped on target tones ("beats") of isochronous tone
      sequences consisting of beats and subdivisions (1:n tapping). A phase
      perturbation was introduced either on a beat or on a subdivision. Both types of
      perturbation elicited a PCR, even though there was no asynchrony associated with
      a subdivision. Moreover, the PCR to a perturbed beat was smaller when an
      unperturbed subdivision followed than when there was no subdivision. The relative
      size of the PCRs to perturbed beats and subdivisions depended on tempo, on
      whether the subdivision was local or present throughout the sequence, and on
      whether or not participants engaged in mental subdivision, but not on whether or
      not taps were made on the subdivision level. The results show that phase
      correction in synchronization depends not merely on asynchronies but on
      perceptual monitoring of multiple temporal references within a metrical
      hierarchy.

PMID- 16786354
TI  - Strength, size and activation of knee extensors followed during 8 weeks of
      horizontal bed rest and the influence of a countermeasure.
AB  - Changes in the quadriceps femoris muscle with respect to anatomical cross
      sectional area (CSA), neural activation level and muscle strength were determined
      in 18 healthy men subjected to 8 weeks of horizontal bed rest (BR) with (n = 9)
      and without (n = 9) resistive vibration exercise (RVE). CSA of the knee extensor
      muscle group was measured with magnetic resonance imaging every 2 weeks during
      bed rest. In the control subjects (Ctrl), quadriceps femoris CSA decreased
      linearly over the 8 weeks of bed rest to -14.1 +/- 5.2% (P < 0.05). This
      reduction was significantly (P < 0.001) mitigated by the exercise paradigm (-3.5
      +/- 4.2%; P < 0.05). Prior to and seven times during bed rest, maximal unilateral
      voluntary torque (MVT) values of the right leg were measured together with neural
      activation levels by means of a superimposed stimulation technique. For Ctrl, MVT
      decreased also linearly over time to -16.8 +/- 7.4% after 8 weeks of bed rest (P
      < 0.01), whereas the exercise paradigm fully maintained MVT during bed rest. In
      contrast to previous reports, the maximal voluntary activation remained unaltered
      for both groups throughout the study. For Ctrl, the absence of deterioration of
      the activation level might have been related to the repeated testing of muscle
      function during the bed rest. This notion was supported by the observation that
      for a subset of Ctrl subjects (n = 5) the MVT of the left leg, which was not
      tested during BR, was reduced by 20.5 +/- 10.1%, (P < 0.01) which was for those
      five subjects significantly (P < 0.05) more than the 11.1 +/- 9.2% (P < 0.01)
      reduction for the right, regularly tested leg.

PMID- 16786355
TI  - Living high-training low: effect on erythropoiesis and maximal aerobic
      performance in elite Nordic skiers.
AB  - The "living high-training low" model (Hi-Lo) may improve aerobic performance in
      athletes, and the main mechanism of this improvement is thought to be augmented
      erythropoiesis. A positive effect of Hi-Lo has been demonstrated previously by
      using altitudes of 2,000-3,000 m. Since the rate of erythropoiesis is altitude
      dependent, we tested whether a higher altitude (3,500 m) during Hi-Lo increases
      erythropoiesis and maximal aerobic performance. Nordic skiers trained for 18 days
      at 1,200 m, while sleeping at 1,200 m in ambient air (control group, n = 5) or in
      hypoxic rooms (Hi-Lo, n = 6; 3 x 6 days at simulated altitudes of 2,500, 3,000
      and finally 3,500 m, 11 h day(-1)). Measurements were done before, during (blood
      samples only) and 2 weeks after the intervention (POST). Maximal aerobic
      performance was examined from VO(2max) and time to exhaustion (T(exh)) at
      vVO(2max) (minimum speed associated with VO(2max)), respectively. Erythropoietin
      and soluble transferrin receptor responses were higher during Hi-Lo, whereas
      reticulocytes did not change. In POST (vs. before): hematological parameters were
      similar to basal levels, as well as red blood cell volume, being 2.68 +/- 0.83 l
      (vs. 2.64+/-0.54 l) in Hi-Lo and 2.62+/-0.57 l (vs. 2.87 +/- 0.59 l) in controls.
      At that time, neither VO(2max) nor T(exh) were improved by Hi-Lo, VO(2max) being
      non-significantly decreased by 2.0% (controls) and 3.7% (Hi-Lo). The present
      results suggest that increasing the altitude up to 3,500 m during Hi-Lo
      stimulates erythropoiesis but does not confer any advantage for maximal O2
      transport.

PMID- 16786356
TI  - Modelling of aerobic and anaerobic energy production during exhaustive exercise
      on a cycle ergometer.
AB  - An extension of the original hyperbolic model (Model-2) was proposed by using
      power output required to elicit maximal oxygen uptake (Pt). This study aimed to
      test this new model (Model-alpha) using mechanical work produced during cycle
      ergometry. Model alpha assumed that power exceeding a critical power (Pc) was met
      partly by the anaerobic metabolism. The parameter alpha was the proportion of the
      power exceeding Pc provided by anaerobic metabolism, while power exceeding Pt was
      exclusively met by anaerobic metabolism. Aerobic power was assumed to rise
      monoexponentially with a time constant tau. The exhaustion was assumed to be
      reached when the anaerobic work capacity W' was entirely utilised. Twelve
      subjects performed one progressive ramp test to assess the power at ventilatory
      threshold (P(VT)) and Pt and five constant-load exercise to exhaustion within 2
      30 min, with one to estimate the maximal accumulated oxygen deficit (MAOD).
      Parameters from Model alpha were fitted with tau equal to 0, 10, 20 and 30 s.
      Results in goodness-of-fit was better than Model-2 whatever the value assumed for
      tau (P < 0.05). The value of tau did not affect much the estimates for P (c) and
      alpha. P (c) estimates were significantly correlated with Pc from Model-2 and
      with P(VT). W' estimates, which were dependent on the value ascribed to tau, were
      not statistically different than MAOD. These two variables were, however, not
      significantly correlated. In conclusion, Model alpha could provide useful
      information on the critical power and the anaerobic contribution according to
      exercise intensity, whereas W' estimates should be used with care because of the
      sensitivity to the assumption on aerobic power kinetics tau.

PMID- 16786359
TI  - [Possible genetic link between Darier's disease and depression. Review of the
      literature and case history].
AB  - Darier's disease is a rare, inherited autosomal dominant skin disorder caused by
      a mutation in the sarcoendoplasmatic reticulum calcium transporter (SERCA)-2
      gene. In a number of pedigrees, Darier's disease closely relates with affective
      disorder. The most likely hypothesis for this is a susceptibility gene for
      affective disorder near the SERCA-2-gene. A 6.5-megabase region could be
      identified as a susceptibility locus. This region constitutes a susceptability
      locus also in affective disorder without Darier's disease. The underlying gene
      has not yet been identified.

PMID- 16786358
TI  - The membrane-cytoskeleton organizer ezrin is necessary for hepatocellular
      carcinoma cell growth and invasiveness.
AB  - PURPOSE: The change of cell mobility is one of the preconditions of tumor
      metastasis. Cell skeleton alteration and rearrangement of F-actin was closely
      related to cell mobility. Ezrin is a membrane-cytoskeleton organizer that can
      mediate the rearrangement and the function of F-actin. In this paper, we
      investigated the effect of ezrin on hepatocellular carcinoma cell growth and
      invasiveness. METHODS: Hepatocellular carcinoma cell lines such as MHCC-1, MHCC97
      H, SF7721, SMMC7721, Hep3B, and HepG2 were chosen in this study. We first
      examined the expression and the distribution of ezrin and F-actin in these cell
      lines using immunofluorescence, RT-PCR, and the western blot. Next we used small
      interfering RNA (siRNA) to down-regulate ezrin expression in MHCC-1, MHCC97-H,
      SF7721, and HepG2 to investigate the role of ezrin in tumor cell growth and
      invasiveness. RESULTS: Our preliminary results showed that the expression of
      ezrin and gamma-actin in MHCC-1, MHCC97-H, and SF7721 with higher metastatic
      potential were obviously up-regulated than those in SMMC7721, Hep3B, and HepG2
      with lower potential. No different expression of beta-actin was found in the
      above tumor cell lines. The outcome of RNAi indicated that decreasing ezrin
      expression can notably inhibit the proliferation of the four hepatocellular
      carcinoma cell lines (p < 0.01, n = 10). The proportion of cells in G2-M phase
      also decreased after RNAi. The number of pseudopods decreased as well after RNAi
      treatment (p < 0.01, n = 5). The mobility and invasiveness of cancer cells
      decreased with decreasing ezrin expression tested by transwell assay (p < 0.01, n
      = 8). CONCLUSION: Ezrin plays an important role in the process of hepatocellular
      carcinoma cell proliferation, migration, and invasiveness.

PMID- 16786357
TI  - The prognostic significance of preoperative plasma levels of osteopontin in
      patients with hepatocellular carcinoma.
AB  - We aimed to evaluate the prognostic value of preoperative plasma osteopontin
      (OPN) levels in 101 patients with hepatocellular carcinoma (HCC) who underwent
      liver resection. Plasma OPN levels were detected by ELISA. The association of
      plasma OPN levels of patients with clinicopathological characteristics, tumor
      recurrence, and survival was analyzed. The median plasma OPN level of patients
      was 176.90 ng/ml (range 13.73-780.00 ng/ml), which was significantly higher than
      that of 24 healthy volunteers (63.74 ng/ml, range 12.20-122.32 ng/ml). Plasma OPN
      levels were significantly different in patients with different numbers of tumor
      nodules (168.18 and 217.11 ng/ml for single and multiple nodules, respectively; P
      = 0.002), different Edmondson's grades (201.24, 168.36, and 503.58 ng/ml for
      grades I, II, and III/IV, respectively; P = 0.015), and different TNM stages
      (168.16, 167.54, and 216.18 ng/ml for stages I, II, and III/IV, respectively; P =
      0.016). Significantly higher plasma OPN levels were found in patients with a
      recurrence of HCC after resection, compared with those without recurrence (213.55
      versus 153.70 ng/ml; P = 0.0013). A higher plasma OPN level was a leading
      independent prognostic factor for both overall survival (OS) and disease-free
      survival (DFS) in univariate and multivariate Cox models. This suggests that the
      preoperative plasma OPN level can be used as a predictive marker for HCC
      recurrence and may be helpful to assess the prognosis of patients with HCC after
      surgery.

PMID- 16786360
TI  - [Generalized anxiety disorder with comorbidity. Treatment with pregabalin].
AB  - The efficacy of pregabalin in treating generalized anxiety disorder (GAD) has
      been shown in recent studies. Our experience and case reports in the present
      publication indicate that pregabalin can be an effective therapeutic option for
      patients with GAD and comorbid psychiatric disorders. Treatment with pregabalin
      should also be considered in patients with partial remission of GAD or
      intolerability of SSRI or SNRI.

PMID- 16786363
TI  - [Effects of hyperbaric oxygen therapy (HBO) during treatment of infected free
      bone transplants. A Case report].
AB  - BACKGROUND: Hyperbaric oxygen therapy (HBO) leads to a significant increase of
      oxygen supply in poorly perfused tissue. Several physiological mechanisms of this
      treatment modality are suitable for having a positive effect on infected large
      autologous free bone transplants. CASE REPORT: In a 49-year-old male with a
      metastasized squamous cell carcinoma of the floor of the mouth radical tumour
      surgery with subsequent radiation was performed. Nine years later an infected
      osteoradionecrosis of the mandible emerged which required a continuity-resection
      with simultaneously performed reconstruction of the mandible using an autologous
      free transplanted iliac bone graft. Four days post surgery wide intraoral
      dehiscence with complete denuding of the bone graft occurred. For this reason
      initiation of an adjuvant hyperbaric oxygen therapy in addition to high dose
      antibiotic therapy and local wound care. Combined therapy led to granulation
      tissue on the surface of the transplanted bone with subsequent epithelization.
      Complete incorporation and conversion of the bone transplant with full
      rehabilitation concerning function and aesthetics was noted. DISCUSSION: Without
      HBO treatment the large volume infected autologous free bone transplant would
      have been lost. Beside other capabilities of HBO the induction of rapid
      neovascularisation and increasing oxygen diffusion radius are the reasons that
      the infected transplant was saved. Only under these conditions it was possible to
      erradicate the bacterial infection effectively with antibiotics.

PMID- 16786364
TI  - Sebaceous lymphadenocarcinoma of parotid gland.
AB  - The sebaceous lymphadenocarcinoma of the salivary glands is extremely rare and
      represents carcinomatous transformation of sebaceous lymphadenoma. There are only
      four reported patients in the medical literature. A patient who presented with a
      recent increase of a left infraauricular mass, of more than 10 years duration,
      underwent surgery. The microscopic examination revealed a typical sebaceous
      lymphadenoma with transition to a sebaceous adenocarcinoma. After postoperative
      adjuvant radiotherapy, the patient remains disease-free at 24 months
      postoperatively. We here report a fifth case of this tumor and the youngest age
      at diagnosis among reported cases.

PMID- 16786362
TI  - Selecting neonates with congenital cytomegalovirus infection for ganciclovir
      therapy.
AB  - OBJECTIVE: The objective of this study is to look for evidence based or
      scientific guidelines for selection of newborns with congenital cytomegalovirus
      (CMV) infection that might benefit from treatment with ganciclovir. MATERIALS AND
      METHODS: A literature search was conducted involving the MEDLINE database and the
      Cochrane Collaboration Library. Abstracts were reviewed to select pertinent
      articles dealing with ganciclovir therapy in neonates. References from selected
      articles as well as from reviews were screened for additional relevant articles.
      In total, 13 case reports (16 patients in all), three descriptive uncontrolled
      studies (20 patients in all), two randomized dose-comparative studies (54
      patients in all) and one randomized controlled study (42 patients) were
      identified. OBSERVATIONS: All reported patients presented with central nervous
      system manifestation of CMV infection. Only the randomized controlled study
      showed a reduction of hearing deterioration in the treated group. Published
      predictors of hearing loss in congenitally CMV infected children allow
      identification of candidates that might benefit from treatment. Studies so far
      are promising but of insufficient number to make evidence based recommendations
      about indications for treatment of congenital CMV. As such, studies are very
      difficult to conduct and treatment of infants at high risk of hearing loss may
      appear justified. There is scientific data to help clinicians in selecting a
      subgroup of infants that is at higher risk of hearing deterioration and therefore
      might benefit the most from ganciclovir therapy.

PMID- 16786361
TI  - A new view on cutaneous dendritic cell subsets in experimental leishmaniasis.
AB  - Because of their anatomical distribution epidermal Langerhans cells (LCs) are
      discussed to be crucial for antigen uptake and subsequent presentation to naive T
      cells in skin-draining lymph nodes. The use of LC-specific markers like Langerin
      or knock-in mice expressing green fluorescent protein under the control of the
      Langerin promotor now facilitates the dissection of LCs from other dendritic cell
      (DC) subsets. Surprisingly, current data indicate that LCs are not generally
      involved in the induction of cellular immune responses. Moreover, the widely
      accepted paradigm postulating that LCs in principle act as T cell activators is
      contested by recent publications. Consequently, the biological role of LCs, in
      particular in cutaneous immune responses, needs to be revisited. The experimental
      model of leishmaniasis represents a suitable model to study the origin of an
      antigen-specific T cell response in mice. With this model the transport and
      presentation of skin derived Leishmania (L.) major antigens can be monitored in
      vivo. Furthermore, the quality of T cell-DC interactions can be determined.
      Considering recent progress in LC research we propose a novel concept of LCs in T
      cell meditated immunity against L. major parasites.

PMID- 16786365
TI  - Effect of topical mitomycin C for antrostomy in rabbit with sinusitis.
AB  - The aim of this study is to evaluate if mitomycin C (MMC), applied topically at
      the site of maxillary antrostomy in experimentally inflamed maxillary sinuses,
      may reduce postoperative ostial stenosis without any harmful effect. Twenty-four
      rabbits with experimentally induced maxillary sinusitis underwent maxillary
      antrostomy bilaterally. MMC at a concentration of 0.4 or 1 mg/ml was applied at
      the site of antrostomy on the right whilst the antrostomy site on the left served
      as the control. Half of each MMC concentration group of animals were killed after
      3 weeks, and the remaining half after 6 weeks. For every rabbit, the areas of
      antrostomies were measured and mucosal specimens around the ostia were obtained
      for microscopic evaluation at the time of antrostomy and killing. Within each MMC
      concentration group, MMC-treated antrostomies were significantly wider than those
      of the controls (P < 0.05), even after 6 weeks. However, comparison of the areas
      of MMC-treated antrostomies between the two MMC concentration groups did not show
      any significant difference (P > 0.05). No systemic side effect or permanent
      mucosal damage was detected. These results suggest that postoperative topical MMC
      at a concentration of 0.4 mg/ml can be used to prolong the patency of maxillary
      antrostomy in an inflammed sinus.

PMID- 16786366
TI  - Parapharyngeal space foreign body.
AB  - We present a case of an unusual toothbrush foreign body in the parapharyngeal
      space in a 1.5-year-old child. Children are most affected by this kind of trauma.
      Quicker and exact diagnosis guarantee proper treatment and recovery. The
      toothbrush had broken and one-third (about 6 cm) of it was left in the child's
      mouth, causing some swallowing problems. We do not observe any injury of
      neurovascular structures or inflammation complications. Under general anesthesia,
      neck exploration was undertaken and the toothbrush removed. External exploration
      of the neck is the method of choice in the treatment of big parapharyngeal space
      foreign body as we demonstrated in our case. This method guarantees a good
      exposure of the neurovascular structures of the neck.

PMID- 16786367
TI  - Structure of peripheral synapses: autonomic ganglia.
AB  - Final motor neurons in sympathetic and parasympathetic ganglia receive synaptic
      inputs from preganglionic neurons. Quantitative ultrastructural analyses have
      shown that the spatial distribution of these synapses is mostly sparse and
      random. Typically, only about 1%-2% of the neuronal surface is covered with
      synapses, with the rest of the neuronal surface being closely enclosed by Schwann
      cell processes. The number of synaptic inputs is correlated with the dendritic
      complexity of the target neuron, and the total number of synaptic contacts is
      related to the surface area of the post-synaptic neuron. Overall, most neurons
      receive fewer than 150 synaptic contacts, with individual preganglionic inputs
      providing between 10 and 50 synaptic contacts. This variation is probably one
      determinant of synaptic strength in autonomic ganglia. Many neurons in
      prevertebral sympathetic ganglia receive additional convergent synaptic inputs
      from intestinofugal neurons located in the enteric plexuses. The neurons support
      these additional inputs via larger dendritic arborisations together with a higher
      overall synaptic density. There is considerable neurochemical heterogeneity in
      presynaptic boutons. Some synapses apparently lack most of the proteins normally
      required for fast transmitter release and probably do not take part in
      conventional ganglionic transmission. Furthermore, most preganglionic boutons in
      the ganglionic neuropil do not form direct synaptic contacts with any neurons.
      Nevertheless, these boutons may well contribute to slow transmission processes
      that need not require conventional synaptic structures.

PMID- 16786368
TI  - Giant reticulospinal synapse in lamprey: molecular links between active and
      periactive zones.
AB  - Deciphering the function of synaptic release sites is central to understanding
      neuronal communication. Here, we review studies of the lamprey giant
      reticulospinal synapse, a model that can be used to dissect synaptic vesicle
      trafficking at single release sites. The presynaptic axon is large and contains
      active zones that are spatially separated from each other. During activity,
      synaptic vesicle membrane is shuttled between the active zone and the periactive
      zone at which endocytosis occurs. Recent studies have shown that the periactive
      zone contains an actin-rich cytomatrix that expands during synaptic activity.
      This cytomatrix has been implicated in multiple functions that include (1)
      activity-dependent trafficking of proteins between the synaptic vesicle cluster
      and the periactive zone, (2) synaptic vesicle endocytosis, and (3) the movement
      of newly formed synaptic vesicles to the vesicle cluster. The actin cytomatrix
      thus provides a link between the active zone and the periactive zone; this link
      appears to be critical for sustained cycling of synaptic vesicles.

PMID- 16786369
TI  - Stereo-EEG in children.
AB  - BACKGROUND: Stereotactic placement of intracerebral multilead electrodes for
      chronic EEG recording of seizures or stereoelectroencephalography (SEEG) was
      introduced 50 years ago at Saint Anne Hospital in Paris, France for the
      presurgical evaluation of patients with drug-resistant focal epilepsy. SEEG
      explorations are indicated whenever the noninvasive tests fail to adequately
      localize the epileptogenic zone (EZ). INDICATIONS: Currently, approximately 35%
      of our operated-on children require a SEEG evaluation. Arrangement of electrodes
      is individualized according to the peculiar needs of each child, to verify a
      predetermined hypothesis of localization of the EZ based on pre-SEEG anatomo
      electro-clinical findings. Multilead intracerebral electrodes are designed to
      sample cortical structures on the lateral, intermediate, and mesial aspect of the
      hemisphere, as well as deep-seated lesions. Stereotactic stereoscopic
      teleangiograms and coregistered 3-D MRI are employed to plan avascular
      trajectories and to accurately target the desired structures. Pre-SEEG
      stereotactic neuroradiology and electrode implantation are usually performed in
      separate procedures. Electrodes are removed once video-SEEG monitoring is
      completed. INTRACEREBRAL ELECTRICAL STIMULATIONS: Intracerebral electrical
      stimulations are used to better define the EZ and to obtain a detailed functional
      mapping of critical cortical and subcortical regions. MORBIDITY: Surgical
      morbidity of SEEG is definitely low in children. SEEG-GUIDED RESECTIVE SURGERY:
      In 90% of evaluated children, SEEG provides a guide for extratemporal or
      multilobar resections. SEEG-guided resective surgery may yield excellent results
      on seizures with 60% of patients in Engel's Class I.

PMID- 16786370
TI  - Multiple subpial transections in pediatric epilepsy: indications and outcomes.
AB  - OBJECTIVE: Multiple subpial transection (MST) is a surgical technique mainly used
      when epileptiform activity arises from eloquent or functional brain cortex. In
      the medical literature, there are relatively few studies reporting the efficacy
      and safety of this procedure in adults and in children. We review the scientific
      rationale, the indications, and the results of this procedure. METHODS:
      Neuroanatomic studies show that the basic functional cortical unit is arranged
      vertically, and epileptic activity spreads horizontally. Minimal cortical unit is
      essential for maintenance of cortical activity. Vertical incisions in the cortex
      interrupt transverse synaptic connections, preventing seizure propagation while
      preserving the vertical column subserving neuronal function. In the past, it has
      been difficult to assess the efficacy of MSTs per se, as they have usually been
      performed together with cortical resection or lesionectomy. After MSTs, studies
      show that 33-46% of treated children are in Engel class I or II. The permanent
      complication rate is low with no permanent language or motor disabilities.
      CONCLUSIONS: MST is a safe procedure with unclear specific efficacy. It has been
      used mainly in conjunction with cortical resection or lesionectomy, when the
      eloquent cortex is involved in the seizure activity. Further prospective studies
      are needed to define the role of MST in epilepsy surgery.

PMID- 16786372
TI  - Clinical image. Air in bone: intraosseous pneumatocyst in a child.

PMID- 16786373
TI  - Epithelioid sarcoma arising on the forearm of a 6-year-old boy: case report and
      review of the literature.
AB  - Epithelioid sarcoma is a rare malignant tumor that occurs mainly in young adults
      and most frequently involves the distal portion of the upper extremities. The
      tumor is particularly rare in children and more frequently involves the head and
      neck; only one case involving the forearm has been reported in a child under 10
      years of age, and he was treated with amputation. We report the case of a 6-year
      old boy with an epithelioid sarcoma of the forearm whose initial management had
      been inappropriate. The patient was ultimately treated with limb sparing surgery.
      Two years later, no local recurrence was evident but pleural metastases were
      detected.

PMID- 16786374
TI  - Axial loading with hyperflexion injury to the atlas resulting in crushed lateral
      masses.
AB  - A 40-year-old man was involved in an ATV accident, in which he landed on the top
      of his head. There was no neurological deficit. A plain radiograph showed
      prevertebral soft tissue swelling at the atlas and axis level. Computed
      tomography (CT) demonstrated vertical fractures of the anterior aspects of both
      lateral masses of the atlas, extending to the junction of the lateral mass with
      the anterior arch bilaterally. There was no lateral offset of the lateral masses.
      The mechanism of injury is believed to be axial loading along with hyperflexion.

PMID- 16786371
TI  - Anesthesia for epilepsy surgery in children.
AB  - BACKGROUND: The perioperative management of infants and children for epilepsy
      surgery should focus on the specific problems unique to the state of the disease,
      age of the child, and operative conditions. A basic understanding of age
      dependent variables and the interaction of anesthetic and surgical procedures are
      essential in minimizing perioperative morbidity and mortality. Specific medical
      conditions that impact the conduct of anesthesia include congenital anomalies,
      chronic anticonvulsant therapies, and evolving coagulopathies. The neurosurgical
      procedure and neurophysiological monitoring will determine the type of anesthetic
      technique to be utilized during surgery. OBJECTIVE: This review will provide a
      systematic approach to pediatric patients undergoing epilepsy surgery.

PMID- 16786376
TI  - Phenotypic and genotypic characterization of coagulase-negative staphylococci
      isolated in blood cultures from patients with haematological malignancies.
AB  - Coagulase-negative staphylococci are the predominant aetiological agents in
      bacteraemic patients hospitalized for haematological malignancies. The aim of
      this study was to determine whether differences exist in the prevalence of icaAB
      genes and in the phenotypic and/or genotypic pattern between blood isolates of
      coagulase-negative staphylococci, interpreted as representing true bacteraemia,
      and contaminant isolates from patients with haematological malignancies. Eighty
      two isolates representing true bacteraemia and 47 contaminant isolates were found
      among 76 patients. The most prevalent species in both groups of patients was
      Staphylococcus epidermidis (n=103; 80%). Biochemical typing using the Phene Plate
      system and genotyping using pulsed-field gel electrophoresis showed a tendency
      towards a more homogeneous pattern among isolates causing true bacteraemia
      compared with contaminant isolates. Two major genotypic groups of S. epidermidis
      were found in both the true bacteraemia group and the contaminant group, with
      concordant pulsotypes found as well. These groups may comprise isolates carrying
      specific virulence factors, but the prevalence of the icaAB genes did not differ
      between the true bacteraemia group and the contaminant group. No significant
      difference was seen between the two study groups regarding clinical symptoms or
      complications, use of central venous catheter, and levels of absolute neutrophil
      count or C-reactive protein.

PMID- 16786377
TI  - Seroprevalence of measles, rubella, and mumps antibodies in Catalonia, Spain:
      results of a cross-sectional study.
AB  - Determination of antibody levels against vaccine-preventable diseases is of great
      value to assess immunization programmes. The objective of this study was to
      determine the prevalence of measles, rubella, and mumps antibodies in
      representative samples of the child and adult population of Catalonia and compare
      the findings to those obtained in 1996. A representative sample of the child and
      adult (>or=15 years) population of Catalonia was studied. Enzyme-linked
      immunosorbent assay techniques were used to determine the presence of antibodies.
      Equivocal results for antibodies against measles and rubella were tested using an
      immunofluorescence technique. To compare proportions, the chi-square test and the
      Fisher's exact test were used. Statistical significance was set at 0.05. Adjusted
      odds ratios were calculated using multiple logistic regression analysis. Samples
      from 2,619 people were analyzed. The global prevalence of antibodies was 98.3%
      for measles, 91.1% for mumps, and 98.1% for rubella. The prevalence of rubella
      antibodies was higher in women than in men (98.8 vs. 97.2%, respectively).
      Compared with the results obtained in the 1996 seroprevalence study, only the
      prevalence of rubella antibodies showed a statistically significant increase in
      men (97.2 vs. 94.6%; p=0.002) and, in particular, in women (98.8 vs. 95.3%;
      p<0.001). The low prevalence of susceptible subjects has already led to the
      elimination of indigenous measles in Catalonia and should allow the elimination
      of indigenous rubella by 2005. The level of antibodies necessary to interrupt the
      transmission of mumps has still not been reached in all age groups.

PMID- 16786378
TI  - Clinical outcomes of bacteremic pneumococcal infections in an area with high
      resistance.
AB  - In a retrospective study designed to gather information in a region with high
      antimicrobial resistance, the outcomes of 216 episodes of laboratory-confirmed
      pneumococcal bacteremia treated in Hong Kong between 1995 and 2001 were assessed.
      The patients had a mean age (+/-standard deviation) of 40+/-33.7 years. In all
      patients, the clinical diagnosis was confirmed by isolation of Streptococcus
      pneumoniae from blood (n=216), cerebrospinal fluid (n=7) and/or other sterile
      sites (n=12). Penicillin nonsusceptibility was found in 37.5% of the isolates
      (20.8% intermediate and 16.7% resistant). Penicillin nonsusceptibility was not a
      risk factor for inpatient mortality (p=0.7), nor did it affect duration of fever
      (p=0.4), requirement for intensive care unit admission (p=0.4) or development of
      suppurative complications (p=0.2). Advanced age (OR 11.3, 95%CI 4.5-28.2,
      p<0.01), critical illness (OR 11.3, 95%CI 4.5-28.2, p<0.001) and discordant
      therapy (OR 4.3, 95%CI 1.7-10.9, p<0.002) involving agents with poor anti
      pneumococcal activity (but not penicillins and broad-spectrum beta-lactam agents)
      were significantly associated with mortality.

PMID- 16786375
TI  - Clinical features and outcome of spontaneous bacterial peritonitis in HIV
      infected cirrhotic patients: a case-control study.
AB  - The aim of this study was to evaluate the clinical characteristics and outcome of
      spontaneous bacterial peritonitis, a serious complication in patients with
      cirrhosis and ascites, in an HIV-infected cirrhotic population. Thirty-five HIV
      infected cirrhotic patients who developed spontaneous bacterial peritonitis
      during a 12-year period were compared with 70 non-HIV-infected cirrhotic
      subjects. Patients were matched according to the date of the first episode of
      spontaneous bacterial peritonitis. A bacteriological diagnosis was made in 37 of
      47 (79%) and in 50 of 97 (52%) episodes in the HIV group and in the non-HIV
      group, respectively (p=0.003), and Streptococcus pneumoniae was isolated more
      frequently in the HIV group (22 vs. 8%, p=0.02). Median survival after the
      initial diagnosis of spontaneous bacterial peritonitis was 2.9 and 14.0 months in
      the HIV group and non-HIV group, respectively. Age (hazard ratio [HR] 1.04; 95%CI
      1.01-1.07), male sex (HR 2.55; 95%CI 1.34-4.83), Child-Pugh score at first
      spontaneous bacterial peritonitis episode (HR 1.29; 95%CI 1.10-1.54), renal
      impairment at first spontaneous bacterial peritonitis episode (HR 2.61; 95%CI
      1.49-4.62), and HIV infection (HR 9.81; 95%CI 4.03-23.84) were independently
      associated with higher long-term mortality after the first diagnosis of
      spontaneous bacterial peritonitis. In conclusion, HIV-infected cirrhotic patients
      with spontaneous bacterial peritonitis have a higher rate of bacteriological
      diagnosis and a more frequent pneumococcal etiology than non-HIV-infected
      subjects. Life expectancy in these patients, once spontaneous bacterial
      peritonitis has developed, is poor. These data are particularly relevant for
      determining the optimal time for liver transplantation in this population.

PMID- 16786379
TI  - Multiplex PCR-ELISA for direct detection of MRSA in nasal swabs advantageous for
      rapid identification of non-MRSA carriers.
AB  - In the study presented here 251 nasal swabs obtained from medical staff were
      directly investigated for MRSA using a commercial multiplex PCR system in
      parallel with conventional culture methods to determine the usefulness of PCR for
      rapid screening. Both methods identified 3.2% (8/251) of specimens as MRSA
      positive; one sample was culture-positive only, and three were PCR-positive only.
      PCR correctly identified 215 of 239 (90%) negative swab samples, but one sample
      with weak cultural growth was not detected and was therefore considered false
      negative. The comparative sensitivity of culture versus PCR was 75% (9/12) versus
      91.6% (11/12). Although PCR had a low positive predictive value (31.4%) its
      negative predictive value was high (99.5%). The results of this study indicate
      the multiplex PCR is suitable for the rapid identification of MRSA-negative
      individuals directly from nasal swabs in populations with a low MRSA prevalence,
      but positive results need to be confirmed by culture.

PMID- 16786380
TI  - Risk factors for bacteriuria due to Pseudomonas aeruginosa or Enterococcus spp in
      patients hospitalized via the emergency department.
AB  - To determine the incidence and risk factors related to isolation of Pseudomonas
      aeruginosa or Enterococcus spp from urine cultures obtained from patients in the
      emergency department (ED), a 1-year prospective study was conducted of all urine
      specimens collected in the ED of a general hospital. Specimens from which one of
      these organisms was isolated at a concentration of >or=10(5) cfu/ml were
      included. Of 744 positive urine cultures, 39 (5%) were P. aeruginosa and 28 (4%)
      Enterococcus spp. Comparison with a control cohort of 80 patients with
      Escherichia coli bacteriuria revealed several univariate indicators for P.
      aeruginosa bacteriuria, including male sex, indwelling catheter, past
      prostatectomy, hospitalization in the previous 2 months and pregnancy;
      multivariate indicators were indwelling catheter (p<0.001) and male sex
      (p<0.001). Enterococcus and P. aeruginosa were significantly more often
      associated with asymptomatic bacteriuria. These data will help clinicians select
      appropriate antibiotic treatment for patients with urinary tract infections.

PMID- 16786381
TI  - Differences in microscopic diagnosis of helminths and intestinal protozoa among
      diagnostic centres.

PMID- 16786382
TI  - [Differential diagnosis of back pain].
AB  - Back pain is one of the most frequent clinical pictures encountered in a
      physician's practice. It can pose a great burden on the individual and in
      addition have a multifactorial origin. It can be caused by intervertebral discs,
      vertebral joints, nerve roots, ligaments, sacroiliac joints, or a combination of
      the above. Back pain, as a symptom of a systemic disease, can also be a warning
      signal of grave disorders such as malignancies or in the event of aortic
      aneurysm. The well-considered choice of appropriate diagnostic procedures and
      suitable treatment requires a thorough knowledge of this multifactorial clinical
      picture.

PMID- 16786383
TI  - [Degenerative diseases of the spine: Rare and often unrecognized causes of pain
      syndromes].
AB  - GOAL: The aim of this article is to describe rare and often unrecognized causes
      of spinal pain syndromes. METHOD: Intervertebral disc degeneration frequently
      appears in early adulthood and can have a symptomatic or asymptomatic course.
      This article discusses incidence, pathophysiology, imaging, and pain
      symptomatology involved in the origin of back pain. RESULTS: Anulus tears are
      often found in asymptomatic individuals but could be implicated in lumbar pain
      symptomatology in correlation with the provocative discography. Transient
      disorders can lead to pseudarthrosis of the iliac bone and to degeneration or to
      a reactive hypermobility with intervertebral disc degeneration in the level
      above. Modic type 1 erosive osteochondrosis is characterized by bone marrow edema
      near the hyaline cartilage end plate, which mostly elicits severe pain and
      results in serious limitations in everyday activities. The most important
      differential diagnosis is spondylodiscitis. Schmorl's nodes can exhibit
      considerable surrounding bone marrow edema that can be mistaken for metastases. A
      combination of MRI and CT should be employed for the diagnostic work-up of
      fatigue fracture of the interarticular portion, which is often overlooked due to
      its location. Synovial cysts of the facet joints can lead to radicular symptoms.
      Insufficiency fracture of the sacrum is frequently mistaken for metastasis due to
      intense scintigraphic enhancement and its signal behavior in MRI. CT provides
      instructive information. CONCLUSION: Differential diagnosis should include less
      common causes such as anulus tears, transient disorders, activated Schmorl's
      nodes, synovial cysts of the facet joints, fatigue fractures of the
      interarticular portion of the spine and the sacrum and distinguish from
      metastases in particular.

PMID- 16786384
TI  - [Inflammatory spine disease as a cause of back pain].
AB  - PURPOSE: The aim of this review is to evaluate the role of inflammatory spine
      disease in patients with chronic back pain. The contribution of imaging
      modalities for the diagnostic evaluation of back pain is discussed. MATERIAL AND
      METHODS: A systematic literature search based on the classification of
      seronegative spondyloarthropathies and rheumatoid arthritis was performed. The
      results of this search and the experiences in a large collective of
      rheumatological patients are analyzed. RESULTS: The prevalence of rheumatoid
      arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The
      etiology of these entities is not fully elucidated. Magnetic resonance imaging is
      increasingly used for early detection and surveillance of therapy with TNF-alpha
      antagonists. DISCUSSION: Bone marrow edema, which is only detectable with MRI,
      represents an early sign of inflammation. Therapy with TNF-alpha antagonists is
      based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI
      is useful for assessment of the effectiveness of anti-inflammatory therapy.

PMID- 16786385
TI  - [Postoperative syndrome after spine surgery].
AB  - Postoperative syndrome after spine surgery, i.e., symptoms or syndromes caused by
      complications or procedure-related consequences, is gaining more and more
      importance. Due to great improvements concerning imaging and operative techniques
      (microsurgery, instrumentation) the total number of spinal surgeries as well as
      their related complications are increasing. Procedure-related postoperative
      complications including neurological deficit syndromes can occur acutely or at a
      later date. Concerning imaging techniques for postoperative evaluation after
      spinal surgery there are several modalities available. Their indications depend
      on complex factors including initial pathology the surgery was performed for,
      kind of surgical technique (surgical approach, instrumentation), anatomy of the
      patient as well as the time between onset of symptoms and surgery. In cases of
      ambiguous findings, the combination of different imaging techniques can be
      instrumental.

PMID- 16786386
TI  - [Vertebroplasty in the treatment of back pain].
AB  - BACKGROUND: Percutaneous vertebroplasty (PVP) represents a minimally invasive
      option which is gaining in importance for the treatment of vertebral compression
      fractures (VCF) and osteolysis of the spine. This article describes the
      indications for its use, peri-interventional imaging, technique, and results of
      PVP. MATERIAL AND METHODS: The current guidelines for performance of PVP are
      explained in accordance with the "Interdisciplinary Consensus Paper on
      Vertebroplasty and Kyphoplasty" of the German Professional Associations and the
      2005 CIRSE Guidelines. The results of our own study carried out in 2002 are
      compared to the complication rates and clinical outcomes reported in the
      literature. RESULTS: Painful osteoporotic VCF and osteolysis within the vertebral
      body due to metastases and multiple myeloma are indications for PVP. Absolute
      contraindications are, in particular, asymptomatic VCF, alleviation of pain by
      drug treatment, therapy-refractory coagulopathies, allergies to cement
      components, and active infections. MRI or CT is indicated before undertaking PVP
      to assess the fracture age, to exclude other causes of pain, and to evaluate the
      posterior edge of the vertebral body. High-quality mono- or biplanar fluoroscopy-
      preferably in combination with CT (fluoroscopy)--is necessary for PVP to minimize
      the risk of cement leakage. A clear reduction in pain [mean reduction of 6.1
      points (VAS)] is achieved in 86-92% of the patients with PVP. Our own study
      treating 58 patients (mean follow-up 323+/-99 days) revealed a clear alleviation
      of pain in 77% [-5.7 points (VAS)]. CONCLUSION: PVP constitutes a safe and
      effective minimally invasive treatment approach to stabilize and reduce acute and
      chronic back pain due to osteoporotic VCF and tumor-associated osteolysis.

PMID- 16786387
TI  - [Balloon kyphoplasty in the treatment of back pain].
AB  - BACKGROUND: Experience of just under 5 years has shown that balloon kyphoplasty
      can be just as successfully employed as the longer-stablished vertebroplasty for
      the treatment of back pain due to recent or prior osteoporotic fractures as well
      as new traumatic fractures. MATERIAL AND METHOD: Among 345 patients with a total
      of 690 treated vertebral bodies, the change in pain symptomatology was analyzed
      for a follow-up period of 12 months in 40 study patients who underwent
      kyphoplasty and a control group of 20 patients. In addition, the pain experienced
      by a further 29 patients with new traumatic vertebral body fractures was
      monitored over a 12-month period. These fractures were partly managed by fixateur
      interne alone and by a combination of fixateur interne and kyphoplasty. RESULTS:
      The 40 patients treated by kyphoplasty had a baseline VAS score of 26.2+/-2.00,
      which increased to 44.4+/-3.11 after 12 months, while the respective scores for
      the control group were 33.6+/-4.21 and 34.3+/-4.35. In the 29 patients with new
      traumatic vertebral body fractures, the initial VAS score was 62 and after 12
      months a distinct reduction of pain was noted with a score of 20 (100 = maximum
      pain, 0 = no pain). The number of times that the 40 patients managed by
      kyphoplasty had to consult their general practitioner was significantly reduced
      by the pain therapy. CONCLUSION: Balloon kyphoplasty verifiably improved the pain
      symptomatology after vertebral fracture over a period of 12 months. Comparison
      with the control group, which received the same osteoporosis drug therapy,
      confirmed the effect of this minimally invasive treatment form.

PMID- 16786388
TI  - [Nucleolysis in the herniated disk].
AB  - Back pain associated with a herniated disk has become an important and increasing
      general health problem in Germany and other industrialized countries. After all
      methods of conservative treatment have been exhausted, nucleolysis may be a
      minimally invasive alternative to surgery. In nucleolysis, chondrolytic
      substances or other substances, which reduce the pressure within the disk by
      other means, are injected into the nucleus pulposus under CT guidance. Among
      various substances, which have been employed for nucleolysis, an ozone-oxygen
      mixture appears to be very promising. The water-binding capacity of ozone results
      in a reduction of pain for several months. Moreover, it has an anti-inflammatory
      effect and results in an increase of perfusion. Ozone is converted into pure
      oxygen in the body and has a low allergic potential. Recent minimally invasive
      therapeutic methods such as percutaneous nucleotomy or laser treatment do not
      result in superior results compared with nucleolysis.

PMID- 16786389
TI  - [Facet blockade, peridural and periradicular pain therapy].
AB  - More than 80% of vertebrogenic lumbar pain is unspecific and can only be
      attributed to a specific anatomic structure with difficulty. The pain can emanate
      from the intervertebral discs, intervertebral and sacroiliac (SI) joints,
      musculature, and ligaments. In a maximum of 7% of cases, the pain is radicular
      (4% due to intervertebral discs and 3% caused by stenoses). In 7-15% of cases,
      the pain's origin is located in the region of the vertebral joints and in up to
      15% in the region of the SI joint. Although the overwhelming majority of pain has
      no clear structural cause, infiltrations of medications and nerve blockades are
      frequently employed. The efficacy of these procedures has however not been
      verified in controlled studies with the exception of epidural injection of
      corticosteroids for radicular pain. Epidural and epiradicular application of
      corticosteroids appear to be effective for radicular pain, at least on a short
      term basis, although controlled studies have yielded controversial results. The
      difficulty lies partly in the exact placement at the affected root for applying
      the medication. This is hardly possible with a caudal injection, while with a
      lumbar peridural injection and periradicular injections it is only possible under
      X-ray control or even better CT guidance.

PMID- 16786390
TI  - Influence of pesticides and herbicides presence on phosphatase activity and
      selected bacterial microbiota of a natural lake system.
AB  - Phosphatase activities (cell-bounded phosphatases "BP" and freely dissolved
      phosphatases "D P") in water samples from a natural lake "Laguna Grande"
      (Antequera, Malaga, Spain) amended with 50 microg/ml of selected insecticides,
      herbicides and fungicide captan were studied under laboratory controlled
      conditions (temperature and agitation). Our data show that dissolved alkaline
      phosphatase was the enzymatic activity that contributed in higher proportion to
      total lake water samples phosphatase status. The presence of organochlorinated
      insecticides (aldrin and lindane), organophosphorous insecticides (dimetoate,
      methidation and methyl-parathion), herbicide atrazine and fungicide captan
      significantly increased phosphatase activities after 28 days of incubation.
      However, these activities were not affected as a consequence of the addition of
      the herbicide simazine to the water samples. Heterotrophic mesophilic and
      psychrophilic aquatic bacteria counts as well as culturable phosphate
      solubilizing microorganisms, increased when the pesticides were added to lake
      water samples with herbicide simazine exception.

PMID- 16786391
TI  - Facial skin surface temperature changes during a "concealed information" test.
AB  - When individuals who commit a crime are questioned, they often show involuntary
      physiological responses to remembered details of that crime. This phenomenon is
      the basis for the concealed information test, in which rarely occurring crime
      related details are embedded in a series of more frequently occurring crime
      irrelevant items while respiratory, cardiovascular, and electrodermal responses
      are recorded. Two experiments were completed to investigate the feasibility of
      using facial skin surface temperature (SST) measures recorded using high
      definition thermographic images as the physiological measure during a concealed
      information test. Participants were randomly assigned to nondeceptive or
      deceptive groups. Deceptive participants completed a mock-crime paradigm. A focal
      plane array thermal imaging radiometer was used to monitor SST while crime
      relevant and crime-irrelevant items were verbally presented to each participant.
      During both experiments, there were significant facial SST differences between
      deceptive and nondeceptive participants early in the analysis interval. In the
      second experiment, hemifacial (i.e., "half-face" divided along the longitudinal
      axis) effects were combined with the bilateral responses to correctly classify
      91.7% of participants. These results suggest that thermal image analysis can be
      effective in discriminating deceptive and nondeceptive individuals during a
      concealed information test.

PMID- 16786392
TI  - Q-method for high-resolution, whole-cell patch-clamp impedance measurements using
      square wave stimulation.
AB  - High-resolution measurements of cell impedance provide invaluable information on
      various cellular processes such as exocytosis, ion channel gating, or
      fertilization. The best recent techniques, although achieving impedance
      resolution at theoretical limits, have limited applicability due to their
      inherent constrains and high complexity. We report here a simple method of high
      resolution impedance measurement, dubbed as the Q-method, based on measurement of
      a charge by integrating the cell current during square wave stimulation and on
      its decomposition into specific components related to segments of the voltage
      stimulus. Simple relations were derived allowing very fast and direct estimation
      of cell impedance parameters. The major advantages of the Q-method are its
      inherently low sensitivity to low-pass filtering, rejection of periodic
      interference signals, automatic on-the-fly adjustment of the stimulation
      frequency for the highest capacitance resolution, and simultaneous high
      resolution low-crosstalk monitoring of membrane resistance, series resistance and
      parasitic capacitance in addition to membrane capacitance. Implementation of the
      Q-method is straightforward with any patch-clamp setup and any cell type.
      Theoretical grounds of the Q-method, including its resolution and the noise of
      individual parameters, are developed and experimentally verified.

PMID- 16786394
TI  - The effect of varying magnitudes of whole-body vibration on several skeletal
      sites in mice.
AB  - It has been reported that whole-body vibration (WBV) is anabolic to trabecular
      bone in animal models and humans. It is likely that this anabolic response does
      not occur uniformly throughout the entire body. Two factors that may affect the
      observed anabolic response are vibration magnitude and skeletal site of interest.
      In this study, mice were loaded with WBV of varying magnitudes. After five weeks
      of loading, bone marrow was flushed from tibias in order to quantify
      osteoprogenitor cells. Staining with alizarin red (an indicator of
      mineralization) showed a significant decrease in percent stained area in the 0.3
      g loaded group compared to the control group and the 1.0 g group. MicroCT
      analysis was performed at five skeletal sites: the proximal tibial metaphysis,
      femoral condyles, distal femoral metaphysis, proximal femur, and L5 vertebral
      body. Increasing magnitudes of WBV were associated with a non-dose-dependent
      increase in trabecular bone volume (BV/TV) at the proximal tibial metaphysis,
      although other sites were unresponsive. There were statistically significant
      increases in BV/TV in the 0.1 g group (32% increase) and 1.0 g group (43%
      increase) compared to control (p < 0.05). The 0.1 g and 1.0 g groups also had
      higher BV/TV than the 0.3 g loaded group. If this non-dose-dependent phenomenon
      is verified by future studies, it suggests that a range of magnitudes should be
      examined for each application of WBV.

PMID- 16786393
TI  - Surfactant copolymers prevent aggregation of heat denatured lysozyme.
AB  - We investigated the ability of certain triblock copolymer surfactant poloxamers
      of the form polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO
      PEO), to prevent formation of stable aggregates of heat denatured hen egg
      lysozyme. Differential scanning calorimetry (DSC) and synchrotron small angle x
      ray scattering (SAXS) experiments were performed to study the thermodynamics and
      solution structures of lysozyme at temperatures between 20 and 90 degrees C in
      the presence and absence of poloxamers with various molecular weights (8.4-14.3
      kDa), but similar hydrophile/hydrophobe (PEO:PPO) ratio of 80%. Poloxmer 188 was
      found to be very effective in preventing aggregation of heat denatured lysozyme
      and those functioned as a synthetic surfactant, thus enabling them to refold when
      the conditions become optimal. For comparison, we measured the ability of 8 kDa
      polyethylene glycol (PEG) to prevent lysozyme aggregation under same conditions.
      The results of these studies suggest that poloxamers are more efficient than PEG
      in preventing aggregation of heat denaturated lysozyme. To achieve equivalence,
      more than an order of magnitude higher concentration of PEG concentration was
      needed. Apparently, the presence of a hydrophobic segment in the poloxamers
      increases their ability to target the hydrophobic region of the unfolded proteins
      and protect them from self association. Given their biocompatibility and the low
      concentrations at which they effectively facilitate refolding of denatured
      proteins, they may be useful in the treatment of burns and other conditions
      resulting in the denaturation of proteins.

PMID- 16786395
TI  - Towards a noninvasive method for determination of patient-specific wall strength
      distribution in abdominal aortic aneurysms.
AB  - The spatial distributions of both wall stress and wall strength are required to
      accurately evaluate the rupture potential for an individual abdominal aortic
      aneurysm (AAA). The purpose of this study was to develop a statistical model to
      non-invasively estimate the distribution of AAA wall strength. Seven parameters-
      namely age, gender, family history of AAA, smoking status, AAA size, local
      diameter, and local intraluminal thrombus (ILT) thickness--were either directly
      measured or recorded from the patients hospital chart. Wall strength values
      corresponding to these predictor variables were calculated from the tensile
      testing of surgically procured AAA wall specimens. Backwards-stepwise regression
      techniques were used to identify and eliminate insignificant predictors for wall
      strength. Linear mixed-effects modeling was used to derive a final statistical
      model for AAA wall strength, from which 95% confidence intervals on the model
      parameters were formed. The final statistical model for AAA wall strength
      consisted of the following variables: sex, family history, ILT thickness, and
      normalized transverse diameter. Demonstrative application of the model revealed a
      unique, complex wall strength distribution, with strength values ranging from 56
      N/cm2 to 133 N/cm2. A four-parameter statistical model for the noninvasive
      estimation of patient-specific AAA wall strength distribution has been
      successfully developed. The currently developed model represents a first attempt
      towards the noninvasive assessment of AAA wall strength. Coupling this model with
      our stress analysis technique may provide a more accurate means to estimate
      patient-specific rupture potential of AAA.

PMID- 16786396
TI  - A signal analysis technique of vestibulo-ocular reflex stimulated with impulsive
      head movements.
AB  - Eye movements have been investigated in several areas of medicine and also
      elsewhere, such as in psychology or even in the development of human-computer
      interfaces. In the last few years we have designed a technique to stimulate,
      measure and analyze vestibulo-ocular reflex eye movements. In the otoneurological
      literature these are seen as a novel and promising means of revealing certain
      disorders and diseases associated with vertigo. Vestibulo-ocular reflex is
      stimulated by impulsive head movements. We developed the present pattern
      recognition technique to detect the stimulus (impulsive head movements) and the
      vestibulo-ocular reflex (response eye movements) generated from signals and to
      compute the latency and the gain values between them. Using our technique to
      calculate these attributes, we obtained clearly different results for a group of
      22 dizzy patients than for a group of 30 healthy subjects.

PMID- 16786397
TI  - Statistical mapping of speckle autocorrelation for visualization of hyperaemic
      responses to cortical stimulation.
AB  - Statistically mapped speckle autocorrelation images (SAR) were used to track the
      hemodynamically active perfusion regions in the rat cortex during and following
      DC current stimulation with high transverse spatial resolution (38 um). The SAR
      images provided a spatio-temporal information about the net activation patterns
      of Cerebral Blood Flow (CBF) changes over a period of time as against those
      changes for each frame interval estimated using spatial contrasts derived from
      the first order spatial statistics. Thus the information about the relative
      maxima of perfusion during a Transient Hyperaemic Episode (THE) across different
      regions in the imaging window could be identified without the need for actually
      having to estimate the spatial contrast maps of the imaged region for each frame
      contained in the time window of observation. With the application of DC
      stimulation, the regions with a high correlation in the temporal fluctuations
      were representative of the areas that underwent least changes in activation. By
      varying the intensity of stimulation, THEs were observed for stimulation current
      densities in the range 0.1-3.8 mA/mm2 using both the derived speckle contrast
      maps and concurrently on a Laser Doppler Flow meter, with its probe positioned 1
      mm from the site of stimulation. For current densities below the lower threshold
      of stimulation, the SAR images revealed an unprecedented reduction in the surge
      amplitude at sites distal to the region of stimulation. This was accompanied by
      an increase in pixel areas representing minimally active regions of perfusion
      ("perfusion islets") with no identifiable peak in the hemodynamic responses
      estimated from speckle contrast variations. The SAR images can be a useful tool
      for visualization of slow wave perfusion dynamics during cortical stimulation.

PMID- 16786398
TI  - Biochemical composition and indigestible oligosaccharides in Phaseolus vulgaris
      L. seeds.
AB  - Common beans have a high nutritional value, but contain galactooligosaccharides
      (GO), which cause flatulence and intestinal discomfort in humans. The biochemical
      composition of ten bean cultivars was determined to select those of high protein
      and low GO contents. The cultivars varied in carbohydrate (47.02-60.17%), GO
      (3.12-5.71%), protein (22.17-33.50%), lipid (1.13-1.81%), moisture (11.42-12.93%)
      and ash contents (4.08-5.61%). 'Mexico 222' presented the highest alpha
      galactosidase activity. Protein and GO contents were positively correlated.
      'Perry Marrow' combined high protein and low GO concentrations, indicating it can
      be used in improvement programs aiming at high-quality cultivars for human
      consumption.

PMID- 16786399
TI  - Optimized RT-PCR method for assaying expression of monocyte chemotactic protein
      type 1 (MCP-1) in rabbit aorta.
AB  - The reverse transcription polymerase chain reaction (RT-PCR) is one of the most
      useful molecular biology methods in opening the way to understanding of the
      mechanisms of atherosclerosis on the gene structure and/or expression level. We
      optimized this technique for assaying expression of the monocyte chemotactic
      protein type 1 (MCP-1) gene in rabbit aorta with respect to the temperature
      profile, yield to cycle number, interference of genomic DNA with the RNA matrix,
      and repeatability. Variability of expression of the constitutive GAPDH gene was
      also examined. The study was done in 18 New Zealand rabbits allocated to two
      groups and fed a standard chow for 2 (S1) or 3 (S2) months. The experiment ended
      with removal of part of the ascending rabbit aorta, from which RNA was isolated.
      The optimal temperature for binding of specific primers to the MCP-1 and GAPDH
      genes was 63 degrees C, and the optimal number of cycles for PCR amplification
      was 22 for MCP-1 and 26 for GAPDH. The GAPDH amplicon size was 465 base pairs in
      the presence or absence of reverse transcriptase showing contamination of the RNA
      matrix with genomic DNA. Repeatability of the RT-PCR method was 8.7%, and
      variability of expression of the GAPDH gene was 7.7%. Thus, RT-PCR adjusted for
      contaminating genomic DNA provides a reliable way of assaying expression of the
      MCP-1 gene in rabbit aorta.

PMID- 16786400
TI  - Mock jurors' reactions to selective presentation of evidence from multiple
      opportunity searches.
AB  - Prior to trial, litigants sometimes conduct broad investigations in which there
      are multiple opportunities to find supportive evidence by chance alone. During
      trial, litigants may selectively present only the most helpful evidence uncovered
      by their investigations. Two experiments examined whether mock jurors appreciate
      that the evidence they hear at trial may be a selective and unrepresentative
      sample of underlying facts. The data suggest that people do understand the
      significance of multiple-opportunity searches for legal inference. However, they
      may not consider the possibility that evidence was strategically selected from a
      larger sample space of facts unless that sample space is identified.

PMID- 16786401
TI  - An archival analysis of actual cases of historic child sexual abuse: A comparison
      of jury and bench trials.
AB  - Logistic regression analyses were used to predict verdicts from 466 Canadian jury
      and 644 Canadian judge-alone criminal trials involving delayed or historic
      allegations of child sexual abuse. Variables in regard to the complainant and
      offence were selected from the legal, clinical, and experimental literatures,
      including mock juror research. Of six variables that had been related to
      decisions reached in mock juror research concerning delayed allegations of child
      sexual abuse (i.e., repressed memory testimony, involvement in therapy, length of
      delay, age of complainant, presence of experts, and frequency of abuse) two (age
      of complainant and presence of expert) predicted verdicts. An additional five
      variables (duration, severity, complainant-accused relationship, threats, and
      complainant gender) were also examined: of these, threats and the complainant
      accused relationship reliably predicted jury verdicts. For judge-alone trials,
      five variables predicted verdict: length of the delay, offence severity, claims
      of repression, the relationship between complainant and accused, and presence of
      an expert. Implications of the jurors' and judges' differential sensitivity to
      these variables for future simulation and archival research are discussed.

PMID- 16786403
TI  - Law and emotion: a proposed taxonomy of an emerging field.
AB  - Scholars from diverse fields have begun to study the intersection of emotion and
      law. The notion that reason and emotion are cleanly separable--and that law
      rightly privileges and admits only of the former--is deeply engrained. Law and
      emotion scholarship proceeds instead from the belief that the legal relevance of
      emotion is both significant and deserving of (and amenable to) close scrutiny. It
      is organized around six approaches, each of which is defined and discussed:
      emotion-centered, emotional phenomenon, emotion theory, legal doctrine, theory of
      law; and legal actor. Drawing on the analytic value of the proposed taxonomy, any
      exploration of law and emotion should strive to identify which emotion(s) it
      takes as its focus; distinguish implicated emotion-driven phenomena; explore
      relevant and competing theories of the emotions; limit itself to a particular
      type of legal doctrine; expose underlying theories of law; and make clear which
      legal actors are implicated. Directions for future research are discussed and
      cross-disciplinary collaboration encouraged.

PMID- 16786404
TI  - Emotions and attributions of legal responsibility and blame: a research review.
AB  - Research on the effects of emotions and moods on judgments of legal
      responsibility and blame is reviewed. Emotions and moods may influence decision
      makers in 3 ways: by affecting their information processing strategies, by
      inclining their judgments in the direction of the valence of the emotion or mood,
      and/or by providing informational cues to the proper decision. A model is
      proposed that incorporates these effects and further distinguishes among various
      affective influences in terms of whether the affect is provoked by a source
      integral or incidental to the judgment task, and whether it affects judgment
      directly (e.g., by providing an informational cue to judgment) or indirectly
      (e.g., by affecting construal of judgment target features, which in turn affects
      the judgment). Legal decision makers' abilities to correct for any affective
      influences they perceive to be undesirable and normative implications for legal
      theory and practice are briefly discussed.

PMID- 16786405
TI  - Chaos in the courtroom reconsidered: emotional bias and juror nullification.
AB  - A widespread presumption in the law is that giving jurors nullification
      instructions would result in "chaos"-jurors guided not by law but by their
      emotions and personal biases. We propose a model of juror nullification that
      posits an interaction between the nature of the trial (viz. whether the fairness
      of the law is at issue), nullification instructions, and emotional biases on
      juror decision-making. Mock jurors considered a trial online which varied the
      presence a nullification instructions, whether the trial raised issues of the
      law's fairness (murder for profit vs. euthanasia), and emotionally biasing
      information (that affected jurors' liking for the victim). Only when jurors were
      in receipt of nullification instructions in a nullification-relevant trial were
      they sensitive to emotionally biasing information. Emotional biases did not
      affect evidence processing but did affect emotional reactions and verdicts,
      providing the strongest support to date for the chaos theory.

PMID- 16786406
TI  - Gruesome evidence and emotion: anger, blame, and jury decision-making.
AB  - Judges assume that gruesome evidence can influence juror verdicts, but little is
      known about the manner in which the influence is manifested. In a 2 x 3 study
      that varied the gruesome content of photographic and verbal evidence, gruesome
      verbal evidence did not influence mock juror emotional states, and had no impact
      on the conviction rate. Mock jurors who saw gruesome photographs, compared with
      those who saw no photographs, reported experiencing significantly more intense
      emotional responses, including greater anger at the defendant. The conviction
      rate when visual evidence in the form of gruesome or neutral photographs was
      included was significantly higher than the conviction rate without photographic
      evidence. Mean ratings of the inculpatory weight of prosecution evidence by mock
      jurors presented with gruesome photographs were significantly higher than those
      by mock jurors who did not view any photographs. Further analyses revealed that
      mock juror anger toward the defendant mediated the influence of the gruesome
      photographs in enhancing the weight of inculpatory evidence.

PMID- 16786407
TI  - Appropriately upset? Emotion norms and perceptions of crime victims.
AB  - Victims who express less emotion in response to a crime are perceived as less
      deserving, less sympathetic, and they have less punishment assigned to the
      offender who committed the crime. This study considers the extent to which
      emotion norms underlie perceptions of victims who testify. Two studies
      investigate the circumstances in which emotional reactions to a crime are seen as
      "unusual" and whether a more general emotion norm underlies responses to victim
      testimony. We test a "victim-role" norm against a "proportionality" norm by
      crossing the severity of victim's emotional response (severe or mild) with the
      seriousness of a crime (serious or less serious). Results across two studies lend
      greater support to the notion that people expect victims to match the intensity
      of their emotional response to the seriousness of the event (i.e., a
      proportionality rule), although we also find instances in which expectations of
      the victim are not strong. Gender of the victim exhibited small and contingent
      effects. We discuss the relevance of emotion norms to legal settings.

PMID- 16786408
TI  - Credibility of the emotional witness: a study of ratings by court judges.
AB  - Previous studies have shown that the emotional behavior displayed during
      testimony may affect the perceived credibility of the witness. The present study
      compares credibility ratings by Norwegian court judges with those made by lay
      people. The participants viewed one of three video-recorded versions of a rape
      victim's statement, role played by a professional actress. The statement was
      given in a free-recall manner with one of three kinds of emotions displayed,
      termed congruent, neutral, and incongruent emotional expression. The results show
      that, in contrast to lay people, the credibility ratings of court judges and
      their votes for a guilty verdict were not influenced by the emotions displayed by
      the witness. Results are discussed in terms of professional expertise.

PMID- 16786409
TI  - Emotion and the law: a framework for inquiry.
AB  - This paper draws on research in social and cognitive psychology to show how
      theories of judgment and decision making that incorporate decision makers'
      affective responses apply to legal contexts. It takes 2 widely used models of
      decision making, the rational actor and lens models, and illustrates their
      utility for understanding legal judgments by using them to interpret research
      findings on juror decision making, people's obedience to the law (e.g., paying
      taxes), and eyewitness memory. The paper concludes with a discussion of the
      advantages of modifying existing approaches to information processing to include
      the influence of affect on how legal actors reach judgments about law and legal
      process.

PMID- 16786410
TI  - A non-linear mixed effect dynamic model incorporating prior exposure and
      adherence to treatment to describe long-term therapy outcome in HIV-patients.
AB  - Long term therapy with antiretroviral agents in HIV-infected patients often
      result in failure to suppress the virus load. Imperfect adherence to prescribed
      antiviral drugs is an important factor explaining the resurgence of virus. A
      better understanding of the factors responsible for the virological failure is
      important for the development of new treatment strategies. Many complex non
      linear models have been developed to describe and simulate the dynamics of HIV-1
      virus. Those complicated viral dynamic models have not been used in clinical
      trials to estimate HIV dynamics parameters, due to their complexity, until the
      recent development of simplification and approximation techniques. The estimation
      of the parameters associated with the dynamics from real data has been mostly
      limited to linearized models that can only explain the decay (suppression) of the
      virus following antiviral treatment. Moreover, no complete characterization of
      typical clinical data in terms of inter-subject variability and identification of
      important covariates effecting HIV-1 dynamics has been attempted. The objective
      of our paper was to develop a hierarchical non-linear mixed effect model
      characterizing inter-subject variability in the long-term response to treatment
      of HIV-1 RNA, and show how the model can be used to quantify the effect of
      important covariates, such as physiological variables, adherence to treatment or
      previous exposure to treatment, on the dynamics of HIV-1 RNA. As an example we
      report the analysis of AIDS clinical trial data from AACTG 398, which shows that
      patients with previous exposure to treatment show faster death rates for HIV-1,
      and that higher adherence to treatment is associated with lower reproductive
      ratio.

PMID- 16786413
TI  - History at the table: conflict in planning in a community in the rural American
      South.
AB  - This article is a case study of problems that emerged during the planning of an
      anti-poverty program in a community in the rural American South in the early
      1990s. Issues of racism, sexism, and classism in the planning process are
      discussed as they are informed by the national welfare reform rhetoric of the
      time, a local context of historical and current White racism, and the historical
      and current identity positions of the local Black planners. The author argues
      that understanding local history is a vital component in planning and
      implementing social programs. The article offers an analysis of the deployment of
      power in the planning of social change projects that can be used to develop
      inclusive planning processes that are responsive to the needs of economically and
      socially oppressed populations.

PMID- 16786411
TI  - Older spouses' cortisol responses to marital conflict: associations with
      demand/withdraw communication patterns.
AB  - We examined 31 older couples' wife demand/husband withdraw communication patterns
      and cortisol responses to marital conflict. Regression analyses indicated that
      wife demand/husband withdraw sequences during conflict related to cortisol
      responses only for wives. Based on a mixed model that accounted for the
      interdependence of spouses' perceptions of communication patterns and outcomes,
      older spouses who reported greater wife demand/husband withdraw patterns in their
      marriage had greater cortisol responses during a conflict discussion; actual
      demand-withdraw did not relate to cortisol responses in this model. Findings
      suggest that perceived communication patterns contribute to neuroendocrine
      responses to marital conflict, and implications for marriage and health research
      with older couples are discussed.

PMID- 16786414
TI  - Lessons learned in developing a research partnership with the Transgender
      community.
AB  - The challenge facing the authors was to develop a relationship with members of
      the Transgender community in a large urban city in order to develop research that
      would benefit this group. The situation is presented from the differing
      perspectives of the three women involved (one Transgender woman and two
      biological women); they provide their accounts of a meeting with key members of
      the Transgender community where the challenge became apparent. During the
      meeting, the issue of representation arose resulting in a discussion of whether
      the research agenda should be focused on a specific subgroup under the
      Transgender umbrella or be open to all members of this diverse and underserved
      group. Reflections on what was learned about the diversity of individuals under
      the Transgender umbrella and the lessons that helped them respond to the
      challenge are discussed.

PMID- 16786412
TI  - Correlation of glottal closure using concurrent ultrasonography and
      nasolaryngoscopy in children: a novel approach to evaluate glottal status.
AB  - OBJECTIVES: Endoscopic procedures to assess aerodigestive symptoms by evaluating
      glottal motion are not practical in neonates because of small nares, respiratory
      difficulties, or additional stress. Our objective was to determine the temporal
      correlation between concurrent nasolaryngoscopy (NLS) and ultrasonography (USG)
      evaluation of glottal motion. METHODS: Simultaneous USG of the glottis was
      performed in 10 subjects (5 males, 5 females, age = 4.5 months to 7.1 years) that
      underwent diagnostic flexible outpatient NLS. The USG transducer was placed on
      the anterior neck at the level of the vocal cords. The video signals from NLS and
      USG were integrated and synchronized into real-time cine loops of 1-min duration.
      RESULTS: Frame-by-frame evaluation of 10,800 frames identifying glottal opening
      and closure time was compared between the two modalities by three observers and
      the timing of glottal closure was marked. Two investigators, blinded to NLS
      images, identified ultrasonographically determined glottal closure with 99% and
      100% accuracy, and the mean probability of missing a closure frame was 0.007 (95%
      CI = 0.0008-0.024). CONCLUSIONS: Temporal characteristics of glottal motion can
      be quantified by USG with perfect reliability and safety. This method can be
      useful in measuring the presence and the duration of laryngeal adduction.

PMID- 16786415
TI  - Article for "diversity stories in community research and action" facing
      resistance in waking up to privilege.
AB  - This article identifies a challenge brought to us while facilitating a diversity
      workshop with adults in a school work setting. Our program involved using the
      video The Color of Fear as a centerpiece of a training to school district staff
      where the goals were to raise awareness and understanding of race, gender and
      class issues, increase understanding of power and privilege, and build alliances
      between people from diverse backgrounds. The challenge came from a white, male
      participant and involved issues of privilege, the intersections of race, class,
      and gender, and resistance to addressing diversity matters. Reflections of what
      worked and didn't work are offered as well as recommendations to other
      facilitators who will face similar challenges.

PMID- 16786416
TI  - Genetic risks to the mother and the infant: assessment, counseling, and
      management.

PMID- 16786418
TI  - The business case for preconception care: methods and issues.
AB  - Only a limited number of economic evaluations have addressed the costs and
      benefits of preconception care. In order to persuade health care providers,
      payers, or purchasers to become actively involved in promoting preconception
      care, it is important to demonstrate the value of doing so through development of
      a "business case". Perceived benefits in terms of organizational reputation and
      market share can be influential in forming a business case. In addition, it is
      standard to include an economic analysis of financial costs and benefits from the
      perspective of the provider practice, payer, or purchaser in a business case. The
      methods, data needs, and other issues involved with preparing an economic
      analysis of the likely financial return on investment in preconception care are
      presented here. This is accompanied by a review or case study of economic
      evaluations of preconception care for women with recognized diabetes. Although
      the data are not sufficient to draw firm conclusions, there are indications that
      such care may yield positive financial benefits to health care organizations
      through reduction in maternal and infant hospitalizations. More work is needed to
      establish how costs and economic benefits are distributed among different types
      of organizations. Also, the optimum methods of delivering preconception care for
      women with diabetes need to be evaluated. Similar assessments should also be
      conducted for other forms of preconception care, including comprehensive care.

PMID- 16786419
TI  - Deliveries from embryos fertilized with spermatozoa obtained from cryopreserved
      testicular tissue.
AB  - AIM: The data of 167 TESE-ICSI-ET cycles performed with fresh or frozen, motile
      or immotile testicular spermatozoa were analyzed, retrospectively. METHODS: The
      outcome measures studied were state/condition of spermatozoa, fertilization,
      embryo developmental, implantation and pregnancy/delivery and abortion rates.
      RESULTS: No differences were found in fertilization, implantation and pregnancy
      rates of oocytes injected with fresh or frozen spermatozoa. However, difference
      was obtained in the fertilization rate of oocytes injected with motile vs. non
      motile spermatozoa (72% vs. 62%; P < 0.04). Difference was also observed in
      embryo development between oocytes injected with fresh vs. frozen spermatozoa
      (83% vs. 75%; P < 0.03). But, no difference was obtained in embryo development
      between oocytes injected with motile vs. immotile spermatozoa. No difference was
      also found in the implantation rate of embryos developed from oocytes injected
      with motile vs. non-motile spermatozoa. No difference was found in abortion rates
      either. CONCLUSIONS: State/condition of injected testicular spermatozoa has
      impact to fertilization and embryo development. Pregnancy/delivery can be
      achieved with frozen/immotile spermatozoa.

PMID- 16786420
TI  - Efficacy of low-dose human chorionic gonadotropin (hCG) in a GnRH antagonist
      protocol.
AB  - PURPOSE: To examine the efficacy of low-dose hCG using a GnRH antagonist
      protocol. METHODS: Prospective randomized study was performed at the Kyono Ladies
      Clinic. One hundred ninety-two women (<40 -years old, <3 previous cycles) were
      randomly assigned to GnRH agonist (buserelin) long protocol (LP, n = 66), GnRH
      antagonist (cetrorelix) with no low-dose hCG protocol (NhCGP, n = 63), or GnRH
      antagonist with low-dose hCG protocol (hCGP, n = 63). RESULTS: The hCGP was
      associated with reduced total amounts of FSH, increased oocyte maturation rate,
      high-quality day 3 embryos rate, and number of frozen embryos. Ovarian
      hyperstimulation syndrome (OHSS) tended to be lower in the GnRH antagonist
      protocol. Pregnancy and implantation rates did not differ significantly between
      study groups. CONCLUSIONS: Daily low-dose hCG supplementation in the late
      follicular phase could improve the outcome in FSH based-GnRH antagonist protocol.
      This protocol, however, does require further modifications, including
      determination of the optimal doses for hCG and gonadotropin pretreatment.

PMID- 16786422
TI  - Ethnicity and clinical psychiatric diagnosis in childhood.
AB  - This paper focuses on whether a consistent difference by ethnicity existed in the
      clinical diagnosis of children and adolescents in two behavioral health service
      environments and reviews plausible explanations for such a difference. Key
      measures were clinical diagnosis and ethnicity, abstracted from the
      administrative dataset of a New Jersey behavioral health care organization during
      2000-2002, and a data collection conducted for the State of Indiana during 1991
      1992. Sample sizes were 5,394 and 10,437, respectively. Only primary diagnoses
      were used in this study, classified into externalizing versus internalizing
      disorders. Logistic regression was performed for the dependent variable of
      presence/absence of an externalizing disorder or internalizing disorder. A main
      effect for ethnicity was found; African American youth received more
      externalizing diagnoses than did European American youth (odds ratio 2.01 (CI:
      1.73-2.33) in one sample and 1.67 (CI: 1.44-1.94) in the other); African American
      youth also received fewer internalizing diagnoses than European American youth
      (odds ratio 0.55 (CI: .48-.63) in one sample and 0.75 (CI:.64-.88) in the other.
      Potential explanations for these findings include: 1. Biopsychosocial origin; 2.
      Clinician bias; 3. Discordant normative behavioral expectations between parents
      and service providers; and 4. Interaction between differential expression of
      underlying pathology and tolerance for such expressions.

PMID- 16786421
TI  - Efficacy of a human embryo transfer medium: a prospective, randomized clinical
      trial study.
AB  - PURPOSE: The aim of this prospective, randomized trial was to evaluate the
      efficacy of Embryo-Glue as a human embryo transfer medium in IVF/ICSI cycles.
      METHOD: A total of 815 nonselected patients undergoing IVF/ICSI treatment between
      September 2003 and February 2004 were randomly allocated into the test (417
      patients) and the control (398 patients) groups. In both groups, embryos were
      cultured in G-1ver 3, supplemented with 10% recombinant human albumin. On the day
      of embryo transfer (day 3), the best or good quality embryos were selected for
      intrauterine transfer. In the test group, the selected embryos were treated with
      EmbryoGlue prior to the transfer, whereas in the control group they were
      transferred without any treatment. RESULTS: The patients' characteristics such as
      age and the number of ART cycles and also the number of patients in each
      indication of infertility and the number of embryos selected for transfer were
      all similar between the two groups. In the test group, the clinical pregnancy
      rate in the tubal factors and the implantation rate in the tubal factors and
      recurrent implantation failures increased significantly compared with those in
      the control group. In the test group, life birth and the triplet delivery rates
      increased significantly compared with those in the control group. CONCLUSION:
      EmbryoGlue is a useful embryo transfer medium, and at least in some infertile
      patients it can improve clinical implantation and ongoing pregnancy rates.

PMID- 16786423
TI  - Short term involuntary psychiatric examination of children in Florida.
AB  - This study describes the use of emergency mental health services by children over
      a 4-year period. Analysis of a statewide database revealed 51,861 or 15% of all
      involuntary examinations were conducted on children. These youth were on average
      a little over 14 years of age and law enforcement officials initiated the
      majority of examinations. The majority of examinations were initiated due to the
      children demonstrating harmful behaviors to themselves or others. One-fifth of
      the children (21%) experienced more than one examination over the 4-year period.
      Areas of future research on this topic are discussed. The implications of the
      nature of examinations and patterns of repeated examinations are discussed.

PMID- 16786424
TI  - Speech sound disorder influenced by a locus in 15q14 region.
AB  - Despite a growing body of evidence indicating that speech sound disorder (SSD)
      has an underlying genetic etiology, researchers have not yet identified specific
      genes predisposing to this condition. The speech and language deficits associated
      with SSD are shared with several other disorders, including dyslexia, autism,
      Prader-Willi Syndrome (PWS), and Angelman's Syndrome (AS), raising the
      possibility of gene sharing. Furthermore, we previously demonstrated that
      dyslexia and SSD share genetic susceptibility loci. The present study assesses
      the hypothesis that SSD also shares susceptibility loci with autism and PWS. To
      test this hypothesis, we examined linkage between SSD phenotypes and
      microsatellite markers on the chromosome 15q14-21 region, which has been
      associated with autism, PWS/AS, and dyslexia. Using SSD as the phenotype, we
      replicated linkage to the 15q14 region (P=0.004). Further modeling revealed that
      this locus influenced oral-motor function, articulation and phonological memory,
      and that linkage at D15S118 was potentially influenced by a parent-of-origin
      effect (LOD score increase from 0.97 to 2.17, P=0.0633). These results suggest
      shared genetic determinants in this chromosomal region for SSD, autism, and
      PWS/AS.

PMID- 16786425
TI  - Strain differences in rewarded discrimination learning using the olfactory tubing
      maze.
AB  - We trained BALB/c Byllco (C), CD-1, SV 129/SvPasCr1 (129 SV), C57BL/6 (B6) and
      DBA/2J (D2) mice using the olfactory tubing maze with the hope of gaining insight
      into behavioral genetics related to learning and memory processes. All strains of
      mice acquired the odor-reward associations using this new task except the D2
      strain. The C, CD-1, and 129 SV consistently remembered the associations from the
      sixth 20-trial training session, reaching 80% +/- 5 correct responses in session
      seven. The B6 mice required one more session to reach 76%, while the D2 mice
      never learned the correct odor-reward associations. All mice learned the paradigm
      and the timing of the task, although the 129 SV mice decreased slower the inter
      trial intervals across sessions. With this new task, D2 mice, with a deficit
      totally devoted to an impairment on learning and memory, can be used as a model
      of hippocampal dysfunction, in some respects like that observed in human amnesic
      patients whose selective hippocampal-dependent memory is deeply impaired. The
      high-scoring strains (C, CD-1, and 129 SV) seem to be ideal in this task to study
      a gene-targeting mutation postulated to reduce behavioral performance, and
      inversely, for D2 mice. The moderate-scoring strain, B6, should be ideal for
      allowing gene-targeting to go either way. In addition, this new task, which
      enables automated training of odor associations, could be used for studying the
      phenomenon of transitivity in mice, as described in rats.

PMID- 16786426
TI  - Precision and bias of a normal finite mixture distribution model to analyze twin
      data when zygosity is unknown: simulations and application to IQ phenotypes on a
      large sample of twin pairs.
AB  - The classification of twin pairs based on zygosity into monozygotic (MZ) or
      dizygotic (DZ) twins is the basis of most twin analyses. When zygosity
      information is unavailable, a normal finite mixture distribution (mixture
      distribution) model can be used to estimate components of variation for
      continuous traits. The main assumption of this model is that the observed
      phenotypes on a twin pair are bivariately normally distributed. Any deviation
      from normality, in particular kurtosis, could produce biased estimates. Using
      computer simulations and analyses of a wide range of phenotypes from the U.K.
      Twins' Early Developments Study (TEDS), where zygosity is known, properties of
      the mixture distribution model were assessed. Simulation results showed that, if
      normality assumptions were satisfied and the sample size was large (e.g., 2,000
      pairs), then the variance component estimates from the mixture distribution model
      were unbiased and the standard deviation of the difference between heritability
      estimates from known and unknown zygosity in the range of 0.02-0.20.
      Unexpectedly, the estimates of heritability of 10 variables from TEDS using the
      mixture distribution model were consistently larger than those from the
      conventional (known zygosity) model. This discrepancy was due to violation of the
      bivariate normality assumption. A leptokurtic distribution of pair difference was
      observed for all traits (except non-verbal ability scores of MZ twins), even when
      the univariate distribution of the trait was close to normality. From an
      independent sample of Australian twins, the heritability estimates for IQ
      variables were also larger for the mixture distribution model in six out of eight
      traits, consistent with the observed kurtosis of pair difference. While the known
      zygosity model is quite robust to the violation of the bivariate normality
      assumption, this novel finding of widespread kurtosis of the pair difference may
      suggest that this assumption for analysis of quantitative trait in twin studies
      may be incorrect and needs revisiting. A possible explanation of widespread
      kurtosis within zygosity groups is heterogeneity of variance, which could be
      caused by genetic or environmental factors. For the mixture distribution model,
      violation of the bivariate normality assumption will produce biased estimates.

PMID- 16786427
TI  - Identification and kinetic characterization of HtDTC, the mitochondrial
      dicarboxylate-tricarboxylate carrier of Jerusalem artichoke tubers.
AB  - Jerusalem artichoke (Helianthus tuberosus L.) tubers were reported to be tolerant
      to cold and freezing. The aim of this study was to perform a kinetic
      characterization of the mitochondrial dicarboxylate-tricarboxylate carrier
      (HtDTC) and to assess a possible involvement of this carrier in the cold
      tolerance of tubers. The HtDTC was purified from isolated mitochondria by
      sequential chromatography on hydroxylapatite/celite and Matrex Gel Orange A. SDS
      gel electrophoresis of the purified fraction showed a single polypeptide band
      with an apparent molecular mass of 31.6 kDa. A polyclonal antibody raised against
      the tobacco DTC cross-reacted with the purified protein on Western blot analysis.
      In gel trypsin, digestion of the purified HtDTC yielded peptides that exhibited
      strong amino acid sequence similarity to previously identified plant DTCs.
      Furthermore, using degenerate primers, a portion of the Htdtc cDNA was amplified
      and sequenced; this cDNA encoded for a protein with high sequence similarity to
      known plant homolog DTCs. When reconstituted in liposomes loaded with
      dicarboxylate (2-oxoglutarate, malate, malonate, succinate, and maleate) or
      tricarboxylate anions (citrate, trans-aconitate, and isocitrate), the purified
      HtDTC transported all these anions in exchange with external [14C]2-oxoglutarate.
      A kinetic characterization of HtDTC was performed: (a) the half-saturation
      constant Km and the Vmax at 25 degrees C of the 2-oxoglutarate/2-oxoglutarate
      exchange by reconstituted HtDTC were found to be 360 microM and 10.9
      micromol/(min mg protein), respectively; (b) the activation energy Ea of the
      succinate/2-oxoglutarate exchange by the reconstituted HtDTC was found to be 50.7
      kJ/mol constant between -5 and 35 degrees C. Similarly, the activation energy Ea
      of succinate respiration of isolated Jerusalem artichoke mitochondria, measured
      between -2 and 35 degrees C, was shown to be constant (65.3 kJ/mol). The
      physiological relevance of kinetic properties and temperature dependence of
      transport activities of HtDTC is discussed with respect to the cold tolerance
      ability of Jerusalem artichoke tubers.

PMID- 16786428
TI  - Cyclosporin A increases mitochondrial calcium uptake capacity in cortical
      astrocytes but not cerebellar granule neurons.
AB  - Isolated brain mitochondria are a heterogeneous mixture from different cell types
      and these subsets may have differing sensitivities to Ca2+-induced membrane
      permeability transition (MPT) and to inhibition of the MPT by cyclosporin A
      (CsA). This study tested the hypothesis that mitochondria within primary cultures
      of astrocytes and neurons exhibit different energy-dependent Ca2+ uptake
      capacities and different degrees to which CsA increases their uptake capacity.
      Astrocytes and neurons were suspended in a cytosol-like medium containing
      respiratory substrates, ATP, and Mg2+ in the presence of digitonin to selectively
      permeabilize the plasma membrane. Uptake of added Ca2+ by mitochondria within the
      cells was measured by Calcium Green 5N fluorescent monitoring of the medium
      [Ca2+]. Permeabilized astrocytes had a fourfold higher Ca2+ uptake capacity,
      relative to neurons and a twofold higher content based on relative contents of
      mitochondria assessed by measurements of mitochondrial DNA and cytochrome oxidase
      subunit 1 protein. In astrocytes the Ca2+ uptake capacity was increased twofold
      by preincubation with 2-5 microM CsA, while in neurons CsA had no effect. Similar
      results were obtained using measurements of the effects of added Ca2+ on
      mitochondrial membrane potential. FK506, a drug similar to CsA but without MPT
      inhibitory activity, had no effect on either cell type. These results are
      consistent with the presence of a calcium-induced MPT in astrocytes, even in the
      presence of ATP, and indicate that the MPT in cerebellar granule neurons is
      resistant to CsA inhibition. Some of the protective effects of CsA in vivo may
      therefore be mediated by preservation of mitochondrial functional integrity
      within astrocytes.

PMID- 16786429
TI  - The effect of a spinal cord hemisection on changes in nitric oxide synthase pools
      in the site of injury and in regions located far away from the injured site.
AB  - 1. The present study was designed to examine the nitric oxide synthase activities
      (constitutive and inducible) in the site of injury in response to Th10-Th11
      spinal cord hemisection and, to determine whether unilateral disconnection of the
      spinal cord influences the NOS pools on the contra- and ipsilateral sides in
      segments located far away from the epicentre of injury. 2. A radioassay detection
      was used to determine Ca(2+)-dependent and inducible nitric oxide synthase
      activities. Somal, axonal and neuropil neuronal nitric oxide synthase was
      assessed by immunocytochemical study. A quantitative assessment of neuronal
      nitric oxide synthase immunoreactivity was made by an image analyser. The level
      of neuronal nitric oxide synthase protein was measured by the Western blot
      analysis. 3. Our data show the increase of inducible nitric oxide synthase
      activity and a decrease of Ca(2+)-dependent nitric oxide synthase activity in the
      injured site analysed 1 and 7 days after surgery. In segments remote from the
      epicentre of injury the inducible nitric oxide synthase activity was increased at
      both time points. Ca(2+)-dependent nitric oxide synthase activity had decreased
      in L5-S1 segments in a group of animals surviving for 7 days. A hemisection
      performed at thoracic level did not cause significant difference in the nitric
      oxide synthase activities and in the level of neuronal nitric oxide synthase
      protein between the contra- and ipsilateral sides in C6-Th1 and L5-S1 segments
      taken as a whole. Significant differences were observed, but only when the spinal
      cord was analysed segment by segment, and/or was divided into dorsal and ventral
      parts. The cell counts in the cervicothoracic (C7-Th1) and lumbosacral (L5-S1)
      enlargements revealed changes in neuronal nitric oxide synthase immunoreactivity
      on the ipsilateral side of the injury. The densitometric area measurements
      confirmed the reduction of somal, neuropil and axonal neuronal nitric oxide
      synthase immunoreactive staining in the ventral part of rostrally oriented
      segments. 4. Our findings provide evidence that the changes in nitric oxide
      synthase pools are limited not only to impact zone, but spread outside the
      original lesion. The regional distribution of nitric oxide synthase activity and
      neuronal nitric oxide synthase immunoreactivity, measured segment by segment
      shows that nitric oxide may play a significant role in the stepping cycle in the
      quadrupeds.

PMID- 16786430
TI  - Characterization of NO/cGMP-mediated responses in identified motoneurons.
AB  - 1. Nitric oxide (NO) is thought to play a neuromodulatory role in the nervous
      system of vertebrate and invertebrate species. In the hornworm Manduca sexta, NO
      mediated signaling has been implicated in behavioral and developmental processes,
      but its exact function in neurons is unknown. In this study, we identify specific
      neurons in the CNS of Manduca larvae that accumulate cGMP in response to
      treatment with NO donors in the presence of cGMP-phosphodiesterase inhibitors.
      Subsets of these neurons were identified as motoneuron-12 (MN12) and
      intersegmental motoneurons (ISMs), which innervate dorsal oblique muscles of the
      larvae. 2. To investigate the physiological role of NO-evoked increases in cGMP
      in these motoneurons we performed intracellular recordings; we found that
      application of NO donors caused an increase in neuronal excitability that was
      characterized by an increase in the spontaneous firing frequency. When action
      potentials and EPSPs were blocked, NO treatment evoked a depolarization of the
      resting membrane potential and a decrease in the measured input resistance in
      both MN12 and the ISMs. 3. Additional experiments with MN12 showed that treatment
      with the cGMP analogue, 8-Br-cGMP mimicked the NO effect on the resting potential
      and the input resistance. Furthermore, MN12 incubation with the NOS inhibitor, L
      NNA, resulted in a small hyperpolarization of the resting potential and an
      increase in the input resistance, and incubation with the sGC inhibitor, ODQ
      blocked the NO-evoked depolarization of MN12. Finally, NO treatment during
      voltage clamping of MN12 evoked an inward positive current. 4. Taken together,
      these results suggest that NO can act as a "gain control" of neuronal
      excitability, which might have an important role in insect behavior.

PMID- 16786431
TI  - Spatiotemporal alterations of the NO/NOS neuronal pools following transient
      abdominal aorta occlusion: morphological and biochemical studies in the rabbit.
AB  - 1. Brief interruption of spinal cord blood flow resulting from transient
      abdominal aortic occlusion may lead to degeneration of specific spinal cord
      neurons and to irreversible loss of neurological function. The alteration of
      nitric oxide/nitric oxide synthase (NO/NOS) pool occurring after ischemic insult
      may play a protective or destructive role in neuronal survival of affected spinal
      cord segments. 2. In the present study, the spatiotemporal changes of NOS
      following transient ischemia were evaluated by investigating neuronal NOS
      immunoreactivity (nNOS-IR), reduced nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPHd) histochemistry, and calcium-dependent NOS (cNOS) conversion
      of [(3)H] l-arginine to [(3)H] l-citrulline. 3. The greatest levels of these
      enzymes and activities were detected in the dorsal horn, which appeared to be
      most resistant to ischemia. In that area, the first significant increase in
      NADPHd staining and cNOS catalytic activity was found immediately after a 15-min
      ischemic insult. 4. Increases in the ventral horn were observed later (i.e.,
      after a 24-h reperfusion period). While the most intense increase in nNOS-IR was
      detected in surviving motoneurons of animals with a shorter ischemic insult (13
      min), the greatest increase of cNOS catalytic activity and NADPHd staining of the
      endothelial cells was found after stronger insult (15 min). 5. Given that the
      highest levels of nNOS, NADPHd, and cNOS were found in the ischemia-resistant
      dorsal horn, and nNOS-IR in surviving motoneurons, it is possible that NO
      production may play a neuroprotective role in ischemic/reperfusion injury.

PMID- 16786432
TI  - Glucocorticoids increase repair potential in a novel in vitro human airway
      epithelial wounding model.
AB  - Airway epithelial damage is a cardinal feature of chronic asthma. Agents which
      enhance epithelial repair without triggering uncontrolled fibrosis of the
      mesenchyme would be predicted to be useful in the management of asthma. We have
      developed a repeat wound model using mucociliated human bronchial epithelial cell
      (HBEC) cultures to define the key pathways involved in airway epithelial repair,
      and to study the effects of potential therapeutic agents on epithelial repair in
      a chronic setting. We show that repair occurs primarily by cell migration to
      close a defect; this process requires activation of the EGF receptor (EGFR) and
      subsequent tyrosine kinase signalling. Migration is accompanied by up-regulation
      of CD44 in motile cells at the wound margins with proliferation of non-migrating
      cells adjacent to the wound area. In long-term studies beta2 adrenoceptor
      agonists and phosphodiesterase (PDE) inhibitors have no effect on repair
      potential, in contrast chronic treatment with the glucocorticoid dexamethasone
      extends the lifespan of repeatedly wounded differentiated cultures. We suggest
      part of the beneficial effects of glucocorticoids in asthma is related to this
      ability to prolong repair potential following repeated episodes of epithelial
      injury.

PMID- 16786433
TI  - Bluetongue virus and double-stranded RNA increase human vascular permeability:
      role of p38 MAPK.
AB  - Endothelial cell (EC) involvement in viral hemorrhagic fevers has been clearly
      established. However, virally activated mechanisms leading to endothelial
      activation and dysfunction are not well understood. Several different potential
      mechanisms such as direct viral infection, alterations in
      procoagulant/anticoagulant balance, and increased cytokine production have been
      suggested. We utilized a model of EC barrier dysfunction and vascular endothelial
      leakage to explore the effect of bluetongue virus (BTV), a hemorrhagic fever
      virus of ruminants, on human lung endothelial cell barrier properties. Infection
      of human lung EC with BTV induced a significant and dose-dependent decrease in
      trans-endothelial electrical resistance (TER). Furthermore, decreases in TER
      occurred in conjunction with cytoskeletal rearrangement, suggesting a direct
      mechanism for viral infection-mediated endothelial barrier disruption.
      Interestingly, double-stranded RNA (dsRNA) mimicked the effects of BTV on
      endothelial barrier properties. Both BTV- and dsRNA-induced endothelial barrier
      dysfunction was blocked by treatment with a pharmacological inhibitor of p38
      MAPK. The induction of vascular permeability by dsRNA treatment or BTV infection
      was concomitent with induction of inflammatory cytokines. Taken together, our
      data suggest that the presence of dsRNA during viral infections and subsequent
      activation of p38 MAPK is a potential molecular pathway for viral induction of
      hemorrhagic fevers. Collectively, our data suggest that inhibition of p38 MAPK
      may be a possible therapeutic approach to alter viral-induced acute hemorrhagic
      diseases.

PMID- 16786434
TI  - Conservation and phylogeny of a novel family of non-Hox genes of the Antp class
      in Demospongiae (porifera).
AB  - A survey across the most basal animal phylum, the Porifera, for the presence of
      homeobox-containing genes led to the isolation of 24 partial or complete homeobox
      sequences from 21 sponge species distributed in 15 families and 6 orders of
      Demospongiae. All the new sequences shared a high identity/similarity with EmH-3
      (Ephydatia muelleri), a non-Hox gene from the Antp class. The Demox sequences,
      EmH-3, and related homeodomains formed a well-supported clade with no true
      affinity with any known bilaterian family, including the Tlx/Hox11 family,
      suggesting that the EmH-3 family of genes, comprising 31 members, represents a
      novel family of non-Hox genes, called the Demox family, widespread among
      Demospongiae. The presence of the Tlx/Hox11 specific signature in the Demox
      family and common regulatory elements suggested that the Demox and Tlx/Hox11
      families are closely related. In the phylogenetic analyses, freshwater
      Haplosclerida appeared as monophyletic, and Haplosclerida and Halichondrida as
      polyphyletic, with a clade comprising Agelas species and Axinella corrugata. As
      for their expression, high levels of Demox transcripts were found in adult
      tissues. Our data add to the number of published poriferan homeobox sequences and
      provide independent confirmation of the current Demospongiae phylogenies.

PMID- 16786435
TI  - Preliminary assessment of the impact of microRNA-mediated regulation on coding
      sequence evolution in mammals.
AB  - Despite prior claims to the contrary, several lines of evidence suggest that
      selection acts on synonymous mutations in mammals. What might be the mechanisms
      for such selection? Here I attempt to quantify the constraints on the evolution
      of the coding sequence resulting from regulation of mRNA by microRNAs (miRNAs)
      that antisense-bind to the coding region of mRNAs. I employ a set of genes
      recently experimentally verified to be the target of a miRNA, all with putative
      antisense pairing domains within the coding sequence. Although very small (
      approximately 22 nucleotides), 2 of 13 pairing domains show evidence of
      significantly slow sequence evolution. This, along with evidence that these genes
      are regulated by the miRNA under consideration, provides the first good candidate
      domains for intra-CDS pairing of a miRNA in mammals. When analyzed en masse, the
      putative pairing domains have a significantly reduced rate of synonymous
      evolution (approximately 35% lower than null). However, given the size and rarity
      of pairing domains within the coding sequence, the effects that such constraint
      has on estimates of the mutation rate are small enough to be ignored (probably
      less than 1% reduction). The pairing sites also have low Ka values and the
      selection on the synonymous sites is unlikely to lead to misleading reports of
      localized high Ka/Ks ratios.

PMID- 16786436
TI  - Molecular cloning of disintegrin-like transcript BA-5A from a Bitis arietans
      venom gland cDNA library: a putative intermediate in the evolution of the long
      chain disintegrin bitistatin.
AB  - We report the cloning and sequence analysis of BA-5A from a venom gland cDNA
      library of the puff adder, Bitis arietans, that encodes a novel ECD-disintegrin
      like domain. BA-5A is a unique PII disintegrin. It contains the 16 cysteine
      residues that are conserved in all known disintegrin-like domains of ADAM
      proteins and snake venom metalloproteinases but lacks the cysteine-rich domain.
      These features suggest that BA-5A may represent an intermediate in the
      evolutionary pathway of the long disintegrin bitistatin and that removal of the
      cysteine-rich domain and loss of the PIII-specific disulfide bond were separate
      events along the structural diversification pathway of disintegrins, the former
      predating the latter. The protein family composition of the Bitis arietans venom,
      as determined by combination of reversed-phase HPLC and proteomic analysis, was
      as follows: Zn(2+)-metalloproteinase (38.5%), serine proteinase (19.5%),
      disintegrin (17.8%), C-type lectin-like (13.2%), PLA(2) (4.3%), Kunitz-type
      inhibitor (4.1%), cystatin (1.7%), and unknown (0.9%). BA-5A could not be
      detected in the venom proteome of Bitis arietans. The occurrence of this very low
      abundance (< 0.05%) or nonexpressed disintegrin transcript indicates a hitherto
      unrecognized structural diversity of this protein family. Whether BA-5A plays a
      physiological role or represents an orphan protein which could eventually evolve
      a role in the adaptation of snakes to changing ecological niches and prey habits
      deserves further investigation.

PMID- 16786437
TI  - Evolution and diversification of RNA silencing proteins in fungi.
AB  - Comprehensive phylogenetic analyses of fungal Argonaute, Dicer, and RNA-dependent
      RNA polymerase-like proteins have been performed to gain insights into the
      diversification of RNA silencing pathways during the evolution of fungi. A wide
      range of fungi including ascomycetes, basidiomycetyes, and zygomycetes possesses
      multiple RNA silencing components in the genome, whereas a portion of ascomycete
      and basidiomycete fungi apparently lacks the whole or most of the components. The
      number of paralogous silencing proteins in the genome differs considerably among
      fungal species, suggesting that RNA silencing pathways have diversified
      significantly during evolution in parallel with developing the complexity of life
      cycle or in response to environmental conditions. Interestingly, orthologous
      silencing proteins from different fungal clades are often clustered more closely
      than paralogous proteins in a fungus, indicating that duplication events occurred
      before speciation events. Therefore, the origin of multiple RNA silencing
      pathways seems to be very ancient, likely having occurred prior to the divergence
      of the major fungal lineages.

PMID- 16786438
TI  - Thermal adaptation of the small subunit ribosomal RNA gene: a comparative study.
AB  - We carried out a comprehensive survey of small subunit ribosomal RNA sequences
      from archaeal, bacterial, and eukaryotic lineages in order to understand the
      general patterns of thermal adaptation in the rRNA genes. Within each lineage, we
      compared sequences from mesophilic, moderately thermophilic, and
      hyperthermophilic species. We carried out a more detailed study of the archaea,
      because of the wide range of growth temperatures within this group. Our results
      confirmed that there is a clear correlation between the GC content of the paired
      stem regions of the 16S rRNA genes and the optimal growth temperature, and we
      show that this correlation cannot be explained simply by phylogenetic relatedness
      among the thermophilic archaeal species. In addition, we found a significant,
      positive relationship between rRNA stem length and growth temperature. These
      correlations are found in both bacterial and archaeal rRNA genes. Finally, we
      compared rRNA sequences from warm-blooded and cold-blooded vertebrates. We found
      that, while rRNA sequences from the warm-blooded vertebrates have a higher
      overall GC content than those from the cold-blooded vertebrates, this difference
      is not concentrated in the paired regions of the molecule, suggesting that
      thermal adaptation is not the cause of the nucleotide differences between the
      vertebrate lineages.

PMID- 16786439
TI  - The molecular phylogeny of a nematode-specific clade of heterotrimeric G-protein
      alpha-subunit genes.
AB  - In animal olfactory systems, odorant molecules are detected by olfactory
      receptors (ORs). ORs are part of the G-protein-coupled receptor (GPCR)
      superfamily. Heterotrimeric guanine nucleotide binding G-proteins (G-proteins)
      relay signals from GPCRs to intracellular effectors. G-proteins are comprised of
      three peptides. The G-protein alpha subunit confers functional specificity to G
      proteins. Vertebrate and insect Galpha-subunit genes are divided into four
      subfamilies based on functional and sequence attributes. The nematode
      Caenorhabditis elegans contains 21 Galpha genes, 14 of which are exclusively
      expressed in sensory neurons. Most individual mammalian cells express multiple
      distinct GPCR gene products, however, individual mammalian and insect olfactory
      neurons express only one functional odorant OR. By contrast C. elegans expresses
      multiple ORs and multiple Galpha subunits within each olfactory neuron. Here we
      show that, in addition to having at least one member of each of the four
      mammalian Galpha gene classes, C. elegans and other nematodes also possess two
      lineage-specific Galpha gene expansions, homologues of which are not found in any
      other organisms examined. We hypothesize that these novel nematode-specific
      Galpha genes increase the functional complexity of individual chemosensory
      neurons, enabling them to integrate odor signals from the multiple distinct ORs
      expressed on their membranes. This neuronal gene expansion most likely occurred
      in nematodes to enable them to compensate for the small number of chemosensory
      cells and the limited emphasis on cephalization during nematode evolution.

PMID- 16786440
TI  - SSADH variation in primates: intra- and interspecific data on a gene with a
      potential role in human cognitive functions.
AB  - In the present study we focus on the nucleotide and the inferred amino acid
      variation occurring in humans and other primate species for mitochondrial NAD(+)
      dependent succinic semialdehyde dehydrogenase, a gene recently supposed to
      contribute to cognitive performance in humans. We determined 2527 bp of coding,
      intronic, and flanking sequences from chimpanzee, bonobo, gorilla, orangutan,
      gibbon, and macaque. We also resequenced the entire coding sequence on 39
      independent chromosomes from Italian families. Four variable coding sites were
      genotyped in additional populations from Europe, Africa, and Asia. A test for
      constancy of the nonsynonymous vs. synonymous rates of nucleotide changes
      revealed that primates are characterized by largely variable d(N)/d(S) ratios. On
      a background of strong conservation, probably controlled by selective
      constraints, the lineage leading to humans showed a ratio increased to 0.42.
      Human polymorphic levels fall in the range reported for other genes, with a
      pattern of frequency and haplotype structure strongly suggestive of
      nonneutrality. The comparison with the primate sequences allowed inferring the
      ancestral state at all variable positions, suggesting that the c.538(C) allele
      and the associated functional variant is indeed a derived state that is
      proceeding to fixation. The unexpected pattern of human polymorphism compared to
      interspecific findings outlines the possibility of a recent positive selection on
      some variants relevant to new cognitive capabilities unique to humans.

PMID- 16786441
TI  - Carotid body tumor resection: does the need for vascular reconstruction worsen
      outcome?
AB  - We evaluated outcomes after carotid body tumor resection (CBR) requiring vascular
      reconstruction. Patients undergoing CBR at an academic medical center between
      1990 and 2005 were identified. Medical records were retrospectively reviewed for
      clinical data, operative details, Shamblin's classification, tumor pathology,
      complications, and mortality. Comparisons were performed between those undergoing
      CBR alone and CBR requiring vascular reconstruction (CBR-VASC). Of the 71 CBRs
      performed in 62 patients, 16 required vascular reconstruction (23%). Although
      there was no difference in mean tumor size (CBR 29.1 +/- 11.9 mm, CBR-VASC 32.5
      +/- 9.9 mm; p = 0.133), carotid body tumors were more commonly Shamblin's I when
      CBR was performed alone (CBR 53% vs. CBR-VASC 25%, p = 0.045) and Shamblin's
      II/III when vascular reconstruction was required (CBR 47% vs. CBR-VASC 75%, p =
      0.045). There was also a significant difference in malignant tumor pathology when
      vascular reconstruction was required (CBR 4.4% vs. CBR-VASC 25%, p = 0.034).
      Cranial nerve dysfunction was higher in patients requiring vascular repair (CBR
      27% vs. CBR-VASC 63%, p = 0.012), but there was no difference in baroreflex
      failure (CBR 7.27% vs. CBR-VASC 0%, p = 0.351), Horner's syndrome (CBR 5.5% vs.
      CBR-VASC 6.25%, p = 0.783), or first bite syndrome (CBR 7.27% vs. CBR-VASC 12.5%,
      p = 0.877). There were no perioperative strokes in either group, and one death
      was unrelated to operation. When required, carotid artery reconstruction at the
      time of CBR can be performed safely. Although cranial nerve dysfunction is more
      common when vascular repair is required, this is more likely related to locally
      advanced disease and tumor pathology rather than operative techniques.

PMID- 16786443
TI  - Supercritical fluid extraction for liquid chromatographic determination of
      pyrazosulfuron-ethyl in soils.

PMID- 16786444
TI  - Impact of fermented brown rice with Aspergillus oryzae intake and concentrations
      of organochlorine pesticides in blood of humans from Japan.

PMID- 16786442
TI  - A new polymer-lipid hybrid nanoparticle system increases cytotoxicity of
      doxorubicin against multidrug-resistant human breast cancer cells.
AB  - PURPOSE: This work is intended to develop and evaluate a new polymer-lipid hybrid
      nanoparticle system that can efficiently load and release water-soluble
      anticancer drug doxorubicin hydrochloride (Dox) and enhance Dox toxicity against
      multidrug-resistant (MDR) cancer cells. METHODS: Cationic Dox was complexed with
      a new soybean-oil-based anionic polymer and dispersed together with a lipid in
      water to form Dox-loaded solid lipid nanoparticles (Dox-SLNs). Drug loading and
      release properties were measured spectrophotometrically. The in vitro
      cytotoxicity of Dox-SLN and the excipients in an MDR human breast cancer cell
      line (MDA435/LCC6/MDR1) and its wild-type line were evaluated by trypan blue
      exclusion and clonogenic assays. Cellular uptake and retention of Dox were
      determined with a microplate fluorometer. RESULTS: Dox-SLNs were prepared with a
      drug encapsulation efficiency of 60-80% and a particle size range of 80-350 nm.
      About 50% of the loaded drug was released in the first few hours and an
      additional 10-20% in 2 weeks. Treatment of the MDR cells with Dox-SLN resulted in
      over 8-fold increase in cell kill when compared to Dox solution treatment at
      equivalent doses. The blank SLN and the excipients exhibited little cytotoxicity.
      The biological activity of the released Dox remained unchanged from fresh, free
      Dox. Cellular Dox uptake and retention by the MDR cells were both significantly
      enhanced (p < 0.05) when Dox was delivered in Dox-SLN form. CONCLUSIONS: The new
      polymer-lipid hybrid nanoparticle system is effective for delivery of Dox and
      enhances its efficacy against MDR breast cancer cells.

PMID- 16786445
TI  - Residual behavior and risk assessment of Spiromesifen (Oberon 240 SC) on eggplant
      (Solanum melonongena L) in India: a multilocational study.

PMID- 16786446
TI  - Organochlorine pesticides in tissues of catfish (Silurus asotus) from Guanting
      Reservoir, People's Republic of China.

PMID- 16786448
TI  - Status of HCH residues in Indian medicinal plant materials.

PMID- 16786447
TI  - Polychlorinated biphenyls in fish species from Guanting Reservoir, Beijing,
      People's Republic of China.

PMID- 16786449
TI  - Bioavailability of polycyclic aromatic hydrocarbons (PAHs) from surficial Lake
      Erie sediments.

PMID- 16786450
TI  - Phthalate esters in sediments from Guanting Reservoir and the Yongding River,
      Beijing, People's Republic of China.

PMID- 16786451
TI  - Nutrient fate in treated wastewater amenity irrigation.

PMID- 16786452
TI  - Distribution and speciation of some metals in mangrove sediments from Jiulong
      river estuary, People's Republic of China.

PMID- 16786453
TI  - Effect of sewage sludge addition on soil quality in terms of metal
      concentrations.

PMID- 16786454
TI  - Spatial distribution and partitioning of heavy metals in surface sediments from
      Yangtze estuary and Hangzhou Bay, People's Republic of China.

PMID- 16786455
TI  - Total mercury and methylmercury accumulation in the muscle tissue of frigate
      (Auxis thazard thazard) and yellow fin (Thunnus albacares) tuna from the Gulf of
      Guinea, Ghana.

PMID- 16786456
TI  - Effects of commercial microbial products on the immune system of Elliptio
      complanata mussels.

PMID- 16786457
TI  - Oil spill remediation techniques can have different impacts on mixed function
      oxygenase enzyme activities in fish.

PMID- 16786458
TI  - Biomarkers in caddisfly larvae of the species Hydropsyche pellucidula (Curtis,
      1834) (Trichoptera: Hydropsychidae) measured in natural populations and after
      short term exposure to fenitrothion.

PMID- 16786459
TI  - Acute toxicity of dichlorvos on fingerling European catfish, Silurus glanis.

PMID- 16786460
TI  - Efficiency of rice bran for removal of di-n-butyl phthalate and its effect on the
      growth inhibition of Selenastrum capricornutum by di-n-butyl phthalate.

PMID- 16786461
TI  - Comparative sensitivity of green algae to herbicides using erlenmeyer flask and
      microplate growth-inhibition assays.

PMID- 16786462
TI  - Effect of cadmium on hematological functions in tilapia (Oreochromis
      mossambicus).

PMID- 16786463
TI  - [New aspects of atrial fibrillation therapy].

PMID- 16786465
TI  - [New antiarrhythmic drugs for therapy of atrial fibrillation: II. Non-ion channel
      blockers].
AB  - The therapeutic approach to atrial fibrillation is difficult and challenging. The
      effect of "classical" antiarrhythmic agents is based on their inhibitory effects
      on various ion channels. However, therapeutic benefit of these agents is often
      limited. The primary goal of this article is to discuss new therapeutic
      approaches using non-ion channel blocking drugs in the treatment of atrial
      fibrillation. Some of the substances discussed in this article have been used
      already in the clinical practice. Others, for example gentherapeutic approaches,
      are still in the experimental state. In contrast to ion channel blocking agents
      their efficacy is based on the suppression of structural remodeling. Hence, it
      can be assumed that due to these effects they may also be beneficial in the
      primary prevention of atrial fibrillation.

PMID- 16786466
TI  - [Electrical and pharmacological strategies for early cardioversion of atrial
      fibrillation].
AB  - Cardioversion of atrial fibrillation as an element of rhythm control strategy is
      indicated in patients with first episode of atrial fibrillation, hemodynamic
      instability, recurrent atrial fibrillation with low probability of spontaneous
      conversion, or severe symptoms. Early cardioversion is performed within 48 h of
      onset of atrial fibrillation. The best point in time is still unknown. It can be
      performed by pharmacological, or, preferentially, by electrical cardioversion.
      The advantages of electrical cardioversion are higher efficacy and no
      proarrhythmic risk, however, short time general anaesthesia is needed. Electrical
      cardioversion is most effective when biphasic shocks are delivered. For
      pharmacological cardioversion, several antiarrhythmic drugs are available which
      have to be considered individually. Thromboembolic risk does not differ between
      the two methods. Early cardioversion and maintenance of sinus rhythm is most
      effective in atrial fibrillation of short duration, normal left atrial size and
      no or only mild structural heart disease.

PMID- 16786464
TI  - [New antiarrhythmic drugs for therapy of atrial fibrillation: I. Ion channel
      blockers].
AB  - During the last ten years we have made substantial progress in our understanding
      of the underlying mechanisms of atrial fibrillation. The high rate associated
      alterations in electrical and structural properties of the atria, referred to as
      atrial remodeling, promote the progression of atrial fibrillation. The
      development of new therapeutic approaches addresses three different directions:
      (i) prevention of atrial remodeling, especially of structural remodeling; (ii)
      increase of long-term efficacy of currently used drugs and improvement of their
      side-effect profile; and (iii) design of atria- and pathology-specific
      antiarrhythmic drugs without concomitant proarrhythmic effects in the ventricles.
      The current review outlines the pathophysiology of atrial fibrillation and
      focuses on electrical remodeling. The properties of new antiarrhythmic drugs for
      atrial fibrillation are discussed in detail.

PMID- 16786467
TI  - [Anticoagulation with atrial fibrillation].
AB  - Atrial fibrillation is associated with a relevant risk for ischemic stroke:
      Observational studies suggest that one in four to five strokes is due to atrial
      fibrillation. Depending on the risk profile of an individual patient, the yearly
      risk for a stroke is between 2% and 14%. Continuous oral anticoagulation is
      indicated if atrial fibrillation is accompanied by at least one additional risk
      factor for thromboembolic complications. This recommendation is supported by
      several large randomized trials. Due to their low therapeutic range, vitamin K
      antagonists (phenprocoumon, warfarin, and others), the most commonly used oral
      anticoagulants, require regular anticoagulation monitoring. If well-controlled
      (international normalized ratio 2-3, in elderly patients preferably 2-2.5), oral
      anticoagulation prevents more than half of ischemic strokes related to atrial
      fibrillation, while bleeding complications are rare. In the follow-up of low risk
      patients (CHADS2-Score 0), oral anticoagulation becomes necessary when risk
      factors for thromboembolic complications develop. If a stroke occurs during oral
      anticoagulation and an INR>2 in a patient with atrial fibrillation, other causes
      than thromboembolic events should be considered. New anticoagulants--especially
      direct thrombin antagonists--are currently evaluated in clinical trials and may
      in the future facilitate anticoagulation in patients with atrial fibrillation.

PMID- 16786469
TI  - [Avoidance of intermittent T-wave oversensing with device programming].
AB  - We report the case of a 35-year-old man who was suffering from severe heart
      failure due to cardiomyopathy. He underwent heart transplantation years ago and
      developed complex ventricular arrhythmias in the following months in combination
      with recurrent episodes of syncope due to hypertrophic non-obstructive
      cardiomyopathy in the transplanted heart, so a dual chamber ICD was implanted.
      Months later repetitive episodes of intermittent T-wave oversensing with
      consecutive activation of the ICD could be observed. Surgical revision of the
      electrode was performed and the patient was closely followed up. One year later,
      further episodes of T-wave oversensing led to multiple inappropriate IDC-shocks.
      A very short AV-conduction time was programmed to allow ventricular capture
      whenever possible, because T-wave oversense after ventricular capture would be
      annotated as single ventricular ectopy not resulting in antitachycardia pacing.
      As a consequence, the patient was free from inappropriate ICD-shocks, but showed
      several shorter episodes of T-wave oversensing. They were all initiated by atrial
      activity that was seen in the refractory period, thus leading to a loss of AV
      synchrony. Programming a very short post ventricular atrial refractory period
      (PVARP) in addition to a short AV-delay led to the complete disappearance of T
      wave oversensing in this patient. During a 9-month follow-up, no further
      tachycardia episodes were detected by the device.

PMID- 16786470
TI  - [Pacemaker quiz, 12th part].

PMID- 16786468
TI  - [Genetics of atrial fibrillation: rare mutations, common variants and clinical
      relevance?].
AB  - Atrial fibrillation (AF) is considered the, by far, the most common arrhythmia of
      man, affecting millions of patients worldwide. The high socio-economic relevance
      is due to several severe complications and therefore requires profound scientific
      research in the field of etiology and treatment options. Atrial fibrillation
      typically occurs in the older patient who often suffers from a number of
      underlying diseases that act as predisposing factors. That genetics contribute
      strongly to this rhythm disorder is therefore not evident at a first glance.
      However, there are a number of investigations that prove familial accumulation
      for lone AF. Furthermore it is remarkable that many older patients suddenly
      develop atrial fibrillation without underlying disease, while others remain in
      sinus rhythm although suffering from a series of risk factors. Considering all
      this, genetic interference becomes most probable. Therefore in the recent past
      remarkable endeavours have been ventured to clarify the genetic basis of both
      lone AF and AF in the context of underlying diseases. For the former, until now
      four different genetic loci and three disease genes have been identified as
      causative. Concerning AF in the general population, mainly studies turning the
      spotlight on single-nucleotide polymorphisms (SNPs) have been applied. It is
      assumed that SNPs in disease-causing genes are distributed differentially among
      healthy and diseased individuals. These differences in frequency have been
      investigated with case-control studies. Up to now six different genes have been
      found to be associated with AF, including the genes for angiotensin-converting
      enzyme, angiotensinogen and several cardiac ion channels. Promising new
      technologies, especially high-throughput SNP genotyping and the genome wide scan
      for new candidate genes using chip arrays capable of genotyping up to 500 000
      SNPs at a time, will multiply the speed to achieve new results. With that the
      possibility, approaches to optimize existing therapies and to open up new
      pathways to treat AF.

PMID- 16786471
TI  - [ECG-quiz, 2nd part].

PMID- 16786474
TI  - Chiral separation of cetirizine by capillary electrophoresis.
AB  - Chiral separation of cetirizine, a second-generation H(1)-antagonist, was studied
      by CD-mediated CE. Several parameters, including pH, CD type, buffer
      concentration, type of co-ion, applied voltage and temperature, were
      investigated. The best conditions for chiral separation were obtained using a 75
      mM triethanolamine-phosphate buffer (pH 2.5) containing 0.4 mg/mL heptakis(2,3
      diacetyl-6-sulfato)-beta-CD and 10% ACN. Online UV detection was performed at 214
      nm, a voltage of 20 kV was applied and the capillary was temperature controlled
      at 25 degrees C by liquid cooling. Hydrodynamic injection was performed for 1 s.
      The method was validated for the quantification of levocetirizine in tablets and
      for enantiomeric purity testing of the drug substance. Selectivity, linearity,
      LOD and LOQ, precision and accuracy were evaluated for both methods. The amount
      of levocetirizine dihydrochloride in the commercially available tablets was
      quantified and was found to be within the specification limits of the claimed
      amount (5 mg). The amount of distomer in levocetirizine drug substance was found
      to be 0.87 +/- 0.09% w/w, which is in agreement with the certificate of analysis
      supplied by the company.

PMID- 16786477
TI  - Capillary electrophoresis for the analysis of small-molecule pharmaceuticals.
AB  - This paper reviews the application of CE to the analysis of small-molecule
      pharmaceuticals. The areas of pharmaceutical analysis covered are enantiomer
      separation, the analysis of small molecules such as amino acids or drug counter
      ions, pharmaceutical assay, determination of related substances and
      physicochemical measurements such as log P and pK(a) of compounds. The different
      electrophoretic modes available and their advantages for pharmaceutical analysis
      are described. Recent applications of CE for each subject area are tabulated with
      electrolyte details.

PMID- 16786478
TI  - Why not using capillary electrophoresis in drug analysis?
AB  - CE and related methods are well-established techniques in the analysis of
      biomolecules, such as DNA and proteins. Even though CE is a rather good
      alternative to HPLC for the evaluation of the impurity profile and the
      enantiomeric purity of a drug, it is rarely applied. This might be due to the
      reservation of national licensing authorities and the pharmacopoeia commissions
      for several reasons. In this review containing some experimental data we report
      on several drug examples which demonstrate the superiority of CE over HPLC in
      special cases, i.e., in the analysis of antibiotics, amino acids and peptides,
      and the determination of enantiomeric purity. However, in order to make the CE
      techniques more suitable for pharmacopoeial purposes the general methods
      describing separation methods have to be complemented with the adjustment of the
      electrophoretic conditions being necessary to satisfy the system suitability
      criteria without fundamentally modifying the methods. Taken together CE should be
      more often applied in drug quality control.

PMID- 16786479
TI  - Micellar electrokinetic capillary chromatographic method for the separation and
      quantitation of multiple amino acids as naphthoxy derivatives in pharmaceutical
      formulations.
AB  - The MEKC method is described for the quantitative analysis of 17 amino acids (AA)
      in pharmaceutical products. The method is based on simply derivatizing the AA
      with (2-naphthoxy)acetyl chloride under mild conditions. The resulting
      derivatives were separated by MEKC with borate buffer (35 mM; pH 9.50) including
      150 mM SDS at the applied voltage of 25 kV in an uncoated capillary (effective
      length, 40 cm) and monitored by UV at 230 nm. The detection limits of the amino
      acid derivatives were in the range of 3.0-8.0 microM (S/N = 3, injection 5.0 s, 6
      895 Pa). The precision (RSD) and accuracy (relative error) of the method for
      intra- and interday analyses of the analytes are all below 5.2%. The amino acid
      derivatives are stable at room temperature for 33 h studied and the molar
      absorptivity of the alanine derivative (used as a model) is stable over a wide pH
      range of 3.00-12.00. This is favorable for monitoring the derivatives in various
      pH by CE or LC. Application of the method to the analysis of multiple AA in a
      liquid injection formulation proved satisfactory.

PMID- 16786480
TI  - Rapid analysis of atorvastatin calcium using capillary electrophoresis and
      microchip electrophoresis.
AB  - In this work, a capillary electrophoretic method for the rapid quantitation of
      atorvastatin (AT) in a lipitor tablet was investigated and developed. Method
      development included studies of the effect of applied potential, buffer
      concentration, buffer pH, and hydrodynamic injection time on the electrophoretic
      separation. The method was validated with regard to linearity, precision,
      specificity, LOD, and LOQ. The optimum electrophoretic separation conditions were
      25 mM sodium acetate buffer at pH 6, with a separation voltage of 25 kV using a
      50 microm capillary of 33 cm total length. Sodium diclofenac was used as an
      internal standard. Analysis of AT in a commercial lipitor tablet by
      electrophoresis gave quite high efficiency, coupled with an analysis time of less
      than 1.2 min in comparison to LC. Once the separation was optimized on capillary,
      it was further miniaturized to a microchip platform, with linear imaging UV
      detection using microchip electrophoresis (MCE). Linear imaging UV detection
      allowed for real-time monitoring of the analyte movement on chip, so that the
      optimum separation time could be easily determined. This microchip
      electrophoretic method was compared to the CE method with regard to speed,
      efficiency, precision, and LOD. This work represents the most rapid and first
      reported analysis of AT using MCE.

PMID- 16786481
TI  - Analysis and validation of the phosphorylated metabolites of two anti-human
      immunodeficiency virus nucleotides (stavudine and didanosine) by pressure
      assisted CE-ESI-MS/MS in cell extracts: sensitivity enhancement by the use of
      perfluorinated acids and alcohols as coaxial sheath-liquid make-up constituents.
AB  - A CE method utilizing triple quadrupole electrospray (ES) MS (MS/MS) detection
      was developed and validated for the simultaneous measurement of nucleoside 5'
      triphosphate and 5'-monophosphate anabolites of the anti-HIV (human
      immunodeficiency virus) didanosine (ddAMP, ddATP) and stavudine (d4TMP, d4TTP),
      among a pool of 14 endogenous 5'-mono-, di-, and triphosphate nucleosides. These
      compounds were spiked and extracted from peripheral blood mononuclear cells
      (PBMCs) which are the sites of HIV replication and drug action. An acetic
      acid/ammonia buffer (pH 10, ionic strength of 40 mM) was selected as running
      electrolyte, and the separation was performed by the simultaneous application of
      a CE voltage of +30 kV and an overimposed pressure of 28 mbar (0.4 psi). The
      application of pressure assistance was needed to provide stable ES conditions for
      successful coupling. The coupling was carried out with a modified sheath-flow
      interface, with one uninterrupted capillary (80 cmx 50 microm id; 192 microm od)
      in a dimension that fits into the ESI needle to get a stable ion spray. Some CE
      MS parameters such as overimposed pressure, sheath-liquid composition, sheath
      liquid and sheath-gas flow rates, ES voltage, and the CE capillary position were
      optimized in order to obtain an optimal sensitivity. The use of perfluorinated
      alcohols and acids in the coaxial sheath-liquid make-up (2,2,2-trifluoroethanol +
      0.2 mM tridecafluoroheptanoic acid) appeared to provide the best MS sensitivity
      and improve the stability of spray. The linearity of the CE-MS and CE-MS/MS
      methods was checked under these conditions. Validation parameters such as
      accuracy, intraday and interday precision, and LOQs were determined in CE-MS/MS
      mode. Finally, the quantitation of d4T-TP and ddA-TP was validated in this CE
      MS/MS system.

PMID- 16786482
TI  - Comparative studies on the analysis of urinary trypsin inhibitor (ulinastatin)
      preparations.
AB  - Urinary trypsin inhibitor (ulinastatin) is a characteristic protein
      pharmaceutical which contains both glycosaminoglycans and N-linked glycans in its
      molecule and has been used for treatment of acute pancreatitis. The comparability
      of ulinastatin preparations of different lots or from different companies was
      studied by using conventional analytical approaches such as SDS-PAGE, cellulose
      acetate membrane electrophoresis, and HP size-exclusion chromatography (SEC) and
      also by using newly developed techniques such as CE and MALDI-TOF MS. The methods
      using SEC and SDS-PAGE according to The Japanese Pharmacopoeia showed similar
      molecular masses for two different preparations, and the estimated molecular
      masses were significantly different from those observed with MALDI-TOF MS. We
      also showed that the electrophoretic methods using cellulose acetate membrane
      electrophoresis and CE can be used for comparability assessments of ulinastatin
      preparations. In addition, we analyzed the unsaturated disaccharides derived from
      glycosaminoglycan (chondroitin 4-sulfate chain) and N-linked oligosaccharides
      attached to ulinastatin by CE after releasing them by enzymatic digestion
      followed by fluorescent labeling with 2-aminoacridone and 2-aminobenzoic acid,
      respectively. The results indicated that carbohydrate chains are important as
      markers for comparability assessments of ulinastatin pharmaceutical preparations.

PMID- 16786483
TI  - Development of off-line and on-line capillary electrophoresis methods for the
      screening and characterization of adenosine kinase inhibitors and substrates.
AB  - Fast and convenient CE assays were developed for the screening of adenosine
      kinase (AK) inhibitors and substrates. In the first method, the enzymatic
      reaction was performed in a test tube and the samples were subsequently injected
      into the capillary by pressure and detected by their UV absorbance at 260 nm. An
      MEKC method using borate buffer (pH 9.5) containing 100 mM SDS (method A) was
      suitable for separating alternative substrates (nucleosides). For the CE
      determination of AMP formed as a product of the AK reaction, a phosphate buffer
      (pH 7.5 or 8.5) was used and a constant current (95 microA) was applied (method
      B). The methods employing a fused-silica capillary and normal polarity mode
      provided good resolution of substrates and products of the enzymatic reaction and
      a short analysis time of less than 10 min. To further optimize and miniaturize
      the AK assays, the enzymatic reaction was performed directly in the capillary,
      prior to separation and quantitation of the product employing electrophoretically
      mediated microanalysis (EMMA, method C). After hydrodynamic injection of a plug
      of reaction buffer (20 mM Tris-HCl, 0.2 mM MgCl2, pH 7.4), followed by a plug
      containing the enzyme, and subsequent injection of a plug of reaction buffer
      containing 1 mM ATP, 100 microM adenosine, and 20 microM UMP as an internal
      standard (I.S.), as well as various concentrations of an inhibitor, the reaction
      was initiated by the application of 5 kV separation voltage (negative polarity)
      for 0.20 min to let the plugs interpenetrate. The voltage was turned off for 5
      min (zero-potential amplification) and again turned on at a constant current of 
      60 microA to elute the products within 7 min. The method employing a
      polyacrylamide-coated capillary of 20 cm effective length and reverse polarity
      mode provided good resolution of substrates and products. Dose-response curves
      and calculated K(i) values for standard antagonists obtained by CE were in
      excellent agreement with data obtained by the standard radioactive assay.

PMID- 16786485
TI  - Proteomic dissection of plant development.
AB  - Plant development is controlled by complex endogenous genetic programs and
      responses to environmental cues. Proteome analyses have recently been introduced
      to plant biology to identify proteins instrumental in these developmental
      processes. To date most plant proteome studies have been employed to generate
      reference maps of the most abundant soluble proteins of plant organs at a defined
      developmental stage. However, proteomics is now also utilized for genetic studies
      comparing the proteomes of different plant genotypes, for physiological studies
      analyzing the influences of exogenous signals on a particular plant organ, and
      developmental studies investigating proteome changes during development.
      Technical advances are now beginning to allow a proteomic dissection of
      individual cell types, thus greatly increasing the information revealed by
      proteome analyses.

PMID- 16786486
TI  - Compensatory effect of the minor Streptomyces lividans type I signal peptidases
      on the SipY major signal peptidase deficiency as determined by extracellular
      proteome analysis.
AB  - The developmentally complex bacterium Streptomyces lividans has the ability to
      produce and secrete a significant amount of protein and possesses four different
      type I signal peptidase genes (sipW, sipX, sipY and sipZ) that are unusually
      clustered in its chromosome. 2-DE and subsequent MS of extracellular proteins
      showed that proteins with typical export signals for type I and type II signal
      peptidases are the main components of the S. lividans secretome. Secretion of
      extracellular proteins is severely reduced in a strain deficient in the major
      type I signal peptidase (SipY). This deficiency was efficiently compensated by
      complementation with any of the other three signal peptidases as deduced from a
      comparison of the corresponding 2-D PAGE patterns with that of the wild-type
      strain.

PMID- 16786487
TI  - Update and challenges on proteomics in rice.
AB  - Rice is not only an important agricultural resource but also a model plant for
      biological research. Our previous review highlighted different aspects of the
      construction of rice proteome database, cataloguing rice proteins of different
      tissues and organelle, differential proteomics using 2-DE and functional
      characterization of some of the proteins identified (Komatsu, S., Tanaka, N.,
      Proteomics 2005, 5, 938-949). In this review, the powerfulness and weaknesses of
      proteomic technologies as a whole and limitations of the currently used
      techniques in rice proteomics are discussed. The information obtained from these
      techniques regarding proteins modification, protein-protein interaction and the
      development of new methods for differential proteomics will aid in deciphering
      more precisely the functions of known and/or unknown proteins in rice.

PMID- 16786488
TI  - Proteomic biomarkers for autoimmune disease.
AB  - Autoimmune diseases affect 3% of the world population, yet the diagnosis and
      classification of autoimmune diseases remain based on clinical examination
      combined with traditional laboratory tests and imaging studies. The development
      of genomic and proteomic technologies provides an unprecedented ability to
      identify novel biosignatures to diagnose, classify, and guide therapeutic
      decision making in patients with autoimmune disease. In this article, we review
      recent advances in proteomics technologies and their application to autoimmune
      disease.

PMID- 16786489
TI  - Automation, parallelism, and robotics for proteomics.
AB  - The speed of the human genome project (Lander, E. S., Linton, L. M., Birren, B.,
      Nusbaum, C. et al., Nature 2001, 409, 860-921) was made possible, in part, by
      developments in automation of sequencing technologies. Before these technologies,
      sequencing was a laborious, expensive, and personnel-intensive task. Similarly,
      automation and robotics are changing the field of proteomics today. Proteomics is
      defined as the effort to understand and characterize proteins in the categories
      of structure, function and interaction (Englbrecht, C. C., Facius, A., Comb.
      Chem. High Throughput Screen. 2005, 8, 705-715). As such, this field nicely lends
      itself to automation technologies since these methods often require large
      economies of scale in order to achieve cost and time-saving benefits. This
      article describes some of the technologies and methods being applied in
      proteomics in order to facilitate automation within the field as well as in
      linking proteomics-based information with other related research areas.

PMID- 16786490
TI  - The use of mass spectrometry for the proteomic analysis of glycosylation.
AB  - Of all protein PTMs, glycosylation is by far the most common, and is a target for
      proteomic research. Glycosylation plays key roles in controlling various cellular
      processes and the modifications of the glycan structures in diseases highlight
      the clinical importance of this PTM. Glycosylation analysis remains a difficult
      task. MS, in combination with modern separation methodologies, is one of the most
      powerful and versatile techniques for the structural analysis of glycoconjugates.
      This review describes methodologies based on MS for detailed characterization of
      glycoconjugates in complex biological samples at the sensitivity required for
      proteomic work.

PMID- 16786491
TI  - Capillary electrophoresis for the characterization of the complex dendrimeric
      contrast agent Gadomer.
AB  - A CE method for the characterization of the complex dendrimeric contrast agent
      Gadomer has been developed and validated. The method was capable of separating
      the target substance Gadomer 24 from related dendrimers containing amino or
      carboxyl functions and from impurities of lower molecular weight. The compounds
      were separated in a fused-silica capillary. The optimized BGE consisted of 15 mM
      sodium phosphate, pH 6.3, containing 0.5 mM hexadecyltrimethylammonium bromide.
      The assay was validated with regard to linearity, specificity, accuracy, LOD and
      LOQ as well as robustness according to the guidelines of the International
      Conference on Harmonization. The method allows the determination of the purity
      and stability of the drug substance Gadomer as well as its injectable
      formulation. On the basis of the present study, a strategy for the quality
      assurance and quality control of the complex dendrimeric drug candidate Gadomer
      may be devised. The method may therefore serve as a key component in a set of
      analytical methodologies designed to assure and control the reproducible quality
      and safety of this innovative product. To the best of our knowledge, this is the
      first work reporting a validated method for the characterization, impurity
      profiling, and stability testing of a dendrimeric agent designed for clinical
      use.

PMID- 16786492
TI  - Analytical method for assessing potential dermal exposure to captan, using whole
      body dosimetry, in small vegetable production units in Argentina.
AB  - An analytical method has been developed that can be used to determine the
      potential dermal exposure (PDE) of workers to the pesticide captan in small-scale
      horticultural production units. The methodology is based on the whole body
      dosimetry technique, using a cotton coverall and cotton gloves as sampling media,
      with protective clothing worn beneath the cotton media to protect the operator.
      The quantitative determination of captan was done by gas chromatography-electron
      capture detector (GC-ECD), with the analytical method validated by measuring
      limits of detection and quantification, linear ranges, sample recovery and
      precision. Special emphasis is placed on factors that affected the stability of
      captan during chromatographic determination. The data generated for potential
      dermal exposure are presented separately for mixing/loading and application
      activities. These data are compared with values obtained with visible tracers
      using a similar field technique. Margin of safety (MOS) values are also
      calculated for the agricultural procedures studied.

PMID- 16786493
TI  - Possible regulatory approaches to comparative risk assessment for pesticides.

PMID- 16786494
TI  - Hazards and uptake of chitin synthesis inhibitors in bumblebees Bombus
      terrestris.
AB  - This research project examined the potential hazards of a major class of insect
      growth regulators (IGRs) to survival, reproduction and larval growth in
      bumblebees Bombus terrestris L. Eight chitin synthesis inhibitors (CSIs) were
      tested: buprofezin, cyromazine, diflubenzuron, flucycloxuron, flufenoxuron,
      lufenuron, novaluron and teflubenzuron. These different IGRs, which are important
      in the control of pest insects in greenhouses, were applied via three different
      routes of exposure under laboratory conditions: dermal contact, and orally via
      the drinking of sugar/water and via pollen. The compounds were tested at their
      respective maximum field recommended concentrations (MFRC) and also in dose
      response assays to calculate LC(50) values. In general, none of the CSIs showed
      acute worker toxicity. However, there was a dramatic reduction in brood
      production, especially after oral treatment with pollen and sugar/water.
      Conspicuously, egg fertility was reduced in all treatments with diflubenzuron and
      teflubenzuron. In addition to egg mortality, the worker bumblebees removed larvae
      from the treated nest, and in most cases these individuals were dead first-second
      instars. Under a binocular microscope, such larvae showed an abnormally formed
      cuticle leading to mechanical weakness and death. In another series of
      experiments using (14)C-diflubenzuron and (14)C-flufenoxuron, cuticular
      penetration in workers was studied for a better understanding of the differences
      in toxicity. With (14)C-diflubenzuron, transovarial transport and accumulation in
      the deposited eggs supported the strong reproductive effects. Overall, the
      present results suggest that CSIs should be applied with caution in combination
      with bumblebees. The compatibility of each compound to be used in combination
      with B. terrestris is discussed in relation to calculated LC(50) values, routes
      of uptake and effects.

PMID- 16786495
TI  - Leaf surface characteristics of apple seedlings, bean seedlings and kohlrabi
      plants and their impact on the retention and rainfastness of mancozeb.
AB  - A study was made of the influence of the upper leaf surface characteristics on
      the retention and rainfastness of the contact fungicide mancozeb with and without
      tank-mix adjuvants (RSO 5 and RSO 60) on apple seedlings, bean seedlings and
      kohlrabi plants. Large differences in roughness, in the amount and composition of
      surface waxes and in the retention and rainfastness of mancozeb were found among
      species. Strong correlations between roughness and total amount of surface waxes
      and mass of C29 alkane in the wax mass were also found. Fungicide retention was
      strongly, negatively correlated with surface roughness, total epicuticular wax,
      amount of C29 alkane and the total mass of alkanes. Rainfastness correlated
      strongly or very strongly with the amount of C28 alcohol and C33 alkane. The
      addition of a more hydrophobic (RSO 5) or a more hydrophilic (RSO 60) adjuvant to
      the spray solution influenced retention and rainfastness, and also altered the
      correlation coefficients. The present results support earlier observations which
      show that the success of adjuvants in enhancing the retention and rainfastness of
      agrochemicals depends on the characteristics of the leaf surface.

PMID- 16786496
TI  - Health, schooling and lifestyle among young adults in Finland.
AB  - This was a longitudinal, general population study based on a Northern Finland
      1966 Birth Cohort, using a structural equation approach to estimate the health
      production function and health input functions for four lifestyle variables
      (smoking, alcohol consumption, exercise and unhealthy diet) for males and
      females. In particular, we examined the productive and allocative effects of
      education on health. We used 15D, a generic measure of health-related quality of
      life, as a single index score measure but we also estimated models for some of
      its dimensions. Among the males, the important factors impacting on health were
      education and all the four lifestyle factors, as well as some exogenous variables
      at 31 years and variables describing parents' background, and health and
      behaviour at 14 years. An increase of five years in schooling increased the
      health score by 0.008, of which about 50% was due to direct effect and 50% due to
      indirect effects. Among the females, education does not impact on health, but
      health was affected by the use of alcohol, exercise and diet, but not by smoking.
      Our results indicate that policy options that increase education among men will
      increase their health indirectly via healthier lifestyles. However, since the
      total effect was rather modest and the direct effect insignificant, an increase
      of schooling is not a cost-effective way to increase health given the present
      high educational level of Finland. The young adults' and particularly women's
      internationally high educational status in Finland might be a reason why we find
      only a modest effect of schooling on health and the non-existence of such effects
      among women.

PMID- 16786497
TI  - Fumigant activity of plant essential oils and components from horseradish
      (Armoracia rusticana), anise (Pimpinella anisum) and garlic (Allium sativum) oils
      against Lycoriella ingenua (Diptera: Sciaridae).
AB  - Plant essential oils from 40 plant species were tested for their insecticidal
      activities against larvae of Lycoriella ingenue (Dufour) using a fumigation
      bioassay. Good insecticidal activity against larvae of L. ingenua was achieved
      with essential oils of Chenopodium ambrosioides L., Eucalyptus globulus Labill,
      Eucalyptus smithii RT Baker, horseradish, anise and garlic at 10 and 5 microL L(
      1) air. Horseradish, anise and garlic oils showed the most potent insecticidal
      activities among the plant essential oils. At 1.25 microL L(-1), horseradish,
      anise and garlic oils caused 100, 93.3 and 13.3% mortality, but at 0.625 microL
      L(-1) air this decreased to 3.3, 0 and 0% respectively. Analysis by gas
      chromatography-mass spectrometry led to the identification of one major compound
      from horseradish, and three each from anise and garlic oils. These seven
      compounds and m-anisaldehyde and o-anisaldehyde, two positional isomers of p
      anisaldehyde, were tested individually for their insecticidal activities against
      larvae of L. ingenua. Allyl isothiocyanate was the most toxic, followed by trans
      anethole, diallyl disulfide and p-anisaldehyde with LC(50) values of 0.15, 0.20,
      0.87 and 1.47 microL L(-1) respectively.

PMID- 16786498
TI  - Informing the efficient use of health care and health care research resources -
      the case of screening for abdominal aortic aneurysm in Sweden.
AB  - BACKGROUND: An analytical framework using Bayesian decision theory and value-of
      information analysis has recently been advocated for the economic evaluation of
      health technologies. The purpose of this study was to apply this framework to
      screening for abdominal aortic aneurysm (AAA) in Sweden and to compare the
      conclusions from this study with the conclusions presented in an assessment
      performed by the Swedish Council of Technology Assessment (SBU). METHODS: A
      probabilistic decision-analytical model was developed to establish the cost
      effectiveness of a screening programme for AAA relative to current clinical
      practice and to calculate the value-of-information. RESULTS: The cost per quality
      adjusted life-year for screening was 9700 euro. The expected value of perfect
      information for the assessment of overall cost-effectiveness was low, suggesting
      little benefit in conducting further research. Expected value of perfect partial
      information indicated that rupture probabilities were associated with the highest
      uncertainty. By contrast, the SBU report concluded there was limited evidence of
      cost-effectiveness and proposed further research. CONCLUSION: The investigated
      screening programme for AAA is likely to be cost-effective and conducting another
      clinical trial is unlikely to add much valuable information to this decision
      problem. These recommendations contrast with the vaguer recommendations from SBU
      that more evidence is required of costs-effectiveness.

PMID- 16786499
TI  - Matching estimates of the impact of over-the-counter emergency birth control on
      teenage pregnancy.
AB  - In this paper, we demonstrate how matching estimators can be used to evaluate
      policy interventions which are implemented in relatively few regions at different
      times. Our technique is based on translating calendar time into 'experimental
      time' to provide a common starting point for entry by different areas into the
      scheme. Such an approach is likely to have many applications, in particular to
      cases of state- or country-level interventions for which only aggregate data are
      available. We illustrate the technique using the case of free over-the-counter
      access to emergency birth control for teenagers at pharmacies in England. We
      construct matching estimates of the impact of this scheme on the under-18
      conception rate in local authorities. Irrespective of either the matching or the
      adjustment procedure, we find no evidence that over-the-counter emergency birth
      control schemes lead to lower teenage pregnancy rates.

PMID- 16786501
TI  - Rational alcohol addiction: evidence from the Russian longitudinal monitoring
      survey.
AB  - Alcohol consumption in Russia is legendary and has been reported to be the third
      leading cause of death in the former Soviet Union after heart disease and cancer.
      Are Russian alcohol consumers rational addicts? This paper uses eight rounds of a
      nationally representative Russian survey spanning the period 1994-2003 to
      estimate a rational addiction (RA) model for alcohol consumption. This is done in
      a panel data setting as well as on a wave-by-wave basis. The profile of the
      Russian drinker finds a huge difference between males and females and the model
      is estimated by gender. We do not find support for the RA model in Russia for
      women. For men, although we find that some implications of the RA model are
      satisfied, we fail to endorse the model empirically on grounds of implausible
      negative estimates of the discount rate.

PMID- 16786500
TI  - Underage alcohol use, delinquency, and criminal activity.
AB  - Since 1988, the minimum legal drinking age (MLDA) has been 21 years for all 50 US
      states. The increasing prevalence of teenagers driving under the influence (DUI)
      of alcohol and the resulting traffic accidents were two main reasons for raising
      the MLDA to 21 years. Following the passage of this legislation, several
      published studies have found that the higher MLDA is associated with a
      significant reduction in both fatal and non-fatal accidents. While the
      relationship between MLDA and DUI events among young adults has been extensively
      studied, less information is available on other potential consequences of
      underage drinking. The present study uses data from the National Epidemiologic
      Survey on Alcohol and Related Conditions (NESARC), a recent nationally
      representative survey, to investigate the effects of underage drinking on a
      variety of delinquency and criminal activity consequences. After controlling for
      the endogeneity of alcohol use where appropriate, we find strong evidence that
      various measures of alcohol consumption are related both to delinquency and to
      criminal activity. However, the findings are not uniform across gender as we find
      striking differences between males and females. These results have interesting
      policy and public health implications regarding underage drinking.

PMID- 16786502
TI  - Dynamics in the use of drugs.
AB  - This paper uses information about prime age individuals living in Amsterdam to
      study the dynamics in the use of tobacco, cannabis, and cocaine. The analysis
      examines transitions from non-use to use, as well as transitions from use to non
      use. Particular attention is given to the effect of the age of onset on quitting
      behavior. The empirical analysis shows that for most of the drugs investigated,
      the earlier individuals start using a particular drug the less likely they are to
      stop using that drug.

PMID- 16786504
TI  - Multiple displacement amplification to create a long-lasting source of DNA for
      genetic studies.
AB  - In many situations there may not be sufficient DNA collected from patient or
      population cohorts to meet the requirements of genome-wide analysis of SNPs,
      genomic copy number polymorphisms, or acquired copy number alternations. When the
      amount of available DNA for genotype analysis is limited, high performance whole
      genome amplification (WGA) represents a new development in genetic analysis. It
      is especially useful for analysis of DNA extracted from stored histology slides,
      tissue samples, buccal swabs, or blood stains collected on filter paper. The
      multiple displacement amplification (MDA) method, which relies on isothermal
      amplification using the DNA polymerase of the bacteriophage phi29, is a recently
      developed technique for high performance WGA. This review addresses new trends in
      the technical performance of MDA and its applications to genetic analyses. The
      main challenge of WGA methods is to obtain balanced and faithful replication of
      all chromosomal regions without the loss of or preferential amplification of any
      genomic loci or allele. In multiple comparisons to other WGA methods, MDA appears
      to be most reliable for genotyping, with the most favorable call rates, best
      genomic coverage, and lowest amplification bias.

PMID- 16786505
TI  - Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene.
AB  - Ornithine transcarbamylase (OTC) deficiency is the most common inherited disorder
      of the urea cycle and is transmitted as an X-linked trait. Defects in the OTC
      gene cause a block in ureagenesis resulting in hyperammonemia, which can lead to
      brain damage and death. Three previous mutation updates for the OTC gene have
      been published, in 1993, 1995, and 2002. The most recent comprehensive update, in
      2002, contained 244 mutations including 13 nondisease-causing mutations and
      polymorphisms. This current update reports 341 mutations, of which 93 have not
      been previously reported, and an additional 29 nondisease-causing mutations and
      polymorphisms. Out of the 341 mutations, 149 were associated with neonatal onset
      of hyperammonemia (within the first week of life), 70 were seen in male patients
      with later onset of hyperammonemia, and 121 were found in heterozygous females
      (one unknown). Along with the reported mutations, residual enzyme activities and
      other pertinent clinical information are included whenever available. Most
      mutations in the OTC gene are specific to a particular family ("private"
      mutations). They are distributed throughout the gene, with a significant paucity
      of mutations in the 32 first codons encoding the "leader" peptide (exon 1 and the
      beginning of exon 2). Almost all mutations in consensus splice sites confer a
      neonatal onset phenotype. Using the current molecular screening methods,
      mutations are found in about 80% of the patients. The remaining patients may have
      mutations in regulatory domains or mutations deep in the introns, which
      constitute 98.5% of the genomic sequence. In addition, a phenocopy of OTC
      deficiency caused by mutations in another unknown gene cannot be excluded.

PMID- 16786506
TI  - Conformational studies of proline-, thiaproline- and dimethylsilaproline
      containing diketopiperazines.
AB  - As proline plays an important role in biologically active peptides, many
      analogues of this residue have been developed to modulate the proportion of cis
      and trans conformers. A correlation between the pyrrolidine ring shape and
      structural properties of proline has been established. Diketopiperazine (DKP) is
      the model of choice to study the influence of the proline ring modification. In
      this contribution, cyclo(Gly-Pro) and two analogues cyclo(Sip-Pro) and cyclo(Thz
      Pro) have been studied with proton NMR. We showed that both analogues with
      heteroatoms in gamma position, silicon and sulfur respectively, display a more
      rigid five-member ring. The usual flexibility of proline ring is restrained in
      both cases and only the two C(beta)-exo and C(beta)-endo conformations are
      observed.

PMID- 16786507
TI  - A quality assessment survey of SNP genotyping laboratories.
AB  - To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA)
      round was organized between 11 laboratories in the Nordic and Baltic countries.
      The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly
      selected SNPs. The methods used by the participating laboratories included all
      major platforms for small- to medium-size SNP genotyping. The laboratories used
      their standard procedures for SNP assay design, genotyping, and quality control.
      Based on the joint results from all laboratories, a consensus genotype for each
      DNA sample and SNP was determined by the coordinator of the survey, and the
      results from each laboratory were compared to this genotype. The overall
      genotyping accuracy achieved in the survey was excellent. Six laboratories
      delivered genotype data that were in full agreement with the consensus genotype.
      The average accuracy per SNP varied from 99.1 to 100% between the laboratories,
      and it was frequently 100% for the majority of the assays for which SNP genotypes
      were reported. Lessons from the survey are that special attention should be given
      to the quality of the DNA samples prior to genotyping, and that a conservative
      approach for calling the genotypes should be used to achieve a high accuracy.

PMID- 16786509
TI  - Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis
      imperfecta type I-IV.
AB  - Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited disorders
      characterized by increased bone fragility, with clinical severity ranging from
      mild to lethal. To date, seven types of OI have been described, based on clinical
      phenotype and histological findings. Most patients with a clinical diagnosis of
      OI type I-IV have a mutation in the COL1A1 or COL1A2 genes which encode the two
      alpha chains of type I collagen, the major component of the bone matrix. Analysis
      of COL1A1 and COL1A2 in a cohort of 83 unrelated patients with OI type I-IV
      identified a total of 62 mutations. Thirty-eight appear novel, 26 in COL1A1, and
      12 in COL1A2, and these are described here. The largest group consists of point
      mutations affecting glycine residues in the triple helical domain of the two
      alpha chains, predicted to disrupt protein folding and structure. This is in
      accordance with previously published data. A doublet GC deletion, an unusual 398
      base deletion predicted to completely remove exon 20 of COL1A2, and a point
      mutation resulting in substitution of a conserved cysteine in the C-terminal
      propeptide are described. In addition rare mutations at the cleavage sites of the
      C-propeptide and the N-terminal signal peptide are described.

PMID- 16786508
TI  - The heterogeneous nature of germline mutations in NF1 patients with malignant
      peripheral serve sheath tumours (MPNSTs).
AB  - Malignant peripheral nerve sheath tumours (MPNSTs) are a major cause of mortality
      in patients with neurofibromatosis 1 (NF1). We have analysed lymphocyte DNA
      samples from 30 NF1 patients with MPNSTs to determine their underlying
      constitutional NF1 gene mutations. Mutations were detected in 27/30 (90%) of
      these patients. NF1 mutations identified included nonsense, missense, frameshift,
      splice site mutation and single or multi-exonic deletions and with no obvious
      clustering of the mutations across the gene. Fourteen of the mutations represent
      novel gene changes. There did not appear to be any relationship between the
      mutation type and the level of clinical severity observed. Of the 20 patients
      with high grade MPNSTs, seven patients had small (<20 bp) and multi-exonic
      deletions and three had small insertions (<20 bp). Several studies have suggested
      that NF1 patients with a constitutional 1.5 Mb deletion of the NF1 gene have an
      increased risk of developing malignant peripheral nerve sheath tumours (MPNSTs).
      None of our patients had a 1.5 Mb deletion. Larger prospective studies are needed
      to ascertain whether there is a different spectrum of NF1 mutations in NF1
      patients with high grade compared to low grade MPNSTs and of patients with the
      1.5Mb deletion, in order to determine the true frequency of MPNST in this sub
      group of NF1 patients.

PMID- 16786510
TI  - A new large CFTR rearrangement illustrates the importance of searching for
      complex alleles.
AB  - The p.Val754Met variant, described in 1996 in a CF patient, has been considered a
      CF mutation. However, biochemical aspects, results of functional studies and,
      finally, the identification of a complex deletion removing exons 3 to 10 and 14b
      to 16 in cis of p.Val754Met in a CF patient, argue against a strong deleterious
      effect. An inventory through the French CF network of patients carrying
      p.Val754Met led to the registration of seven patients (CF: n=4; idiopathic
      chronic pancreatitis: n=3) and six healthy individuals, all heterozygous for the
      variation. Extensive CFTR gene analysis was carried out, including the search for
      large rearrangements and other possible mutations. The complex deletion, whose
      breakpoints are described here, was found only in the four CF patients, in
      association with the same haplotype. This data, added to the fact that the
      p.[Phe508del]+[Val754Met] genotype was found in a healthy individual, bring
      further arguments against the association of p.Val754Met with CF. We thus suggest
      looking for a possible complex allele whenever p.Val754Met is detected and
      considering it neutral regarding genetic counseling when found in isolation.

PMID- 16786511
TI  - Genetic variability, haplotypes, and htSNPs for exons 1 at the human UGT1A locus.
AB  - UDP-Glucuronosyltransferases (UGTs) are a superfamily of enzymes responsible for
      glucuronidation of xenobiotics and endobiotics. Genetic polymorphisms have been
      identified in the promoter and exonic regions of several UGT genes. The UGT1As on
      chromosome 2q37 have unique exons 1 but share the remainder of their coding
      sequence. We screened exon 1 of each of the nine functional UGT1As in Asians
      (n=46) and Caucasians (n=92) with the aim of determining linkage disequilibrium
      (LD) and haplotypes across the entire locus in both populations. For
      polymorphisms in UGT 1A3, 1A4, 1A5, 1A7, and 1A8, we observed significant
      differences in the allele frequency between the two populations. The haplotype
      block structure across the UGT1A locus was constructed using all 83 polymorphisms
      and showed four and five haplotype blocks in Caucasians and Asians, respectively.
      There was long-distance LD between UGT pairs: 1A8 and 1A10; 1A1 and 1A3; 1A1 and
      1A6; 1A6 and 1A7; and 1A7 and 1A9. Whereas both ethnic groups shared some
      haplotype-tagging SNPs (htSNPs), Caucasians and Asians also had unique htSNPs.
      This was partly due to the fact that rare variants (<5% allele frequency) were
      included in our analyses. Haplotypes with frequencies >5% represented only 60% of
      Caucasian and 65% of Asian UGT1A haplotypes. Differences in haplotype
      distribution patterns suggest individual and ethnic differences in
      glucuronidation capacity.

PMID- 16786512
TI  - Identification of a novel mutation of SH3BP2 in cherubism and demonstration that
      SH3BP2 mutations lead to increased NFAT activation.
AB  - We describe a novel missense mutation (Aspartic acid to Asparagine, p.D419N
      (g.1371G>A, c.1255G>A) within exon 9 of SH3BP2 in a patient with cherubism, an
      autosomal dominant syndrome characterized by excessive osteoclastic bone
      resorption of the jaw. Two siblings and the father were carriers but lacked
      phenotypic features. Transient expression of p.D419N (c.1255G>A), as well as
      three previously described exon 9 mutations from cherubism patients (p.R415Q
      (c.1244G>A), p.D420E (c.1259G>A), and p.P418R (c.1253C>G)) increased activity of
      NFAT (nuclear factor of activated T-cells), an osteoclastogenic mediator,
      indicating that cherubism results from gain of function mutations in SH3BP2.

PMID- 16786514
TI  - Werner syndrome and mutations of the WRN and LMNA genes in France.
AB  - Werner syndrome (WS) is a pleiotropic disease of premature aging involving short
      stature, tight, atrophied, and/or ulcerated skin; a characteristic 'birdlike'
      facies and high, squeaky or hoarse voice; premature greying and thinning of the
      hair; and early onset cataracts. Additional common symptoms include diabetes
      mellitus, hypogonadism, osteoporosis, osteosclerosis of the digits, soft tissue
      calcification, premature atherosclerosis, rare or multiple neoplasms, malformed
      teeth, and flat feet. Diagnosis can be difficult due to the variable presentation
      and rarity of the disorder. Transmission is usually autosomal recessive. The WS
      gene, WRN, is member of the RecQ DNA helicase family. Biallelic mutations of WRN
      are responsible for most patients. Although heterozygous missense mutations in
      the LMNA gene have been observed in severely affected WS patients, this only
      accounts for a small fraction of non-WRN patients. Eighteen WS cases were
      referred to us for molecular analysis. Eleven had definite and three had probable
      WS according to the University of Washington Registry clinical criteria. All
      exons of the WRN gene and their splice junctions were sequenced. Of the fourteen
      definite or probable cases, 11 had one or more WRN mutation. Thirteen different
      mutations were found, and ten of these were previously undescribed. There were
      few phenotypic differences between patients with WRN mutation(s) and those who
      met clinical criteria though lacking WRN mutations. However, patients with
      mutations tended to have more symptoms overall, and mutations were not observed
      in the two cases with cardiomyopathy.

PMID- 16786513
TI  - McArdle disease: the mutation spectrum of PYGM in a large Italian cohort.
AB  - Deficiency of the muscle isozyme of glycogen phosphorylase is causative of
      McArdle disease or Glycogen storage disease type V (GSD-V), the most common
      autosomal recessive disorder of glycogen metabolism. The typical clinical
      presentation is characterized by exercise intolerance with cramps, and recurrent
      myoglobinuria. To date, 46 mutations in the PYGM gene have been detected in GSD-V
      patients. We report the mutational spectrum in 68 Italian patients. We identified
      30 different mutations in the PYGM gene, including 19 mutations that have not
      been reported previously. The novel mutations include: eight missense mutations
      (c.475G>A, p.G159R; c.689C>G, p.P230R; c.1094C>T, p.A365E; c.1151C>A, p.A384D;
      c.1182C>T, p.R428C; c.1471C>T, p.R491C; c.2444A>C, p.D815A; c.2477G>C, p.W826S),
      two nonsense mutations (c.1475G>A, p.W492X; c.1627A>T, p.K543X), five splice site
      mutations (c.855 +1G>C; c.1092 +1G>A; c. 1093-1G>T; c.1239 +1G>A; c.2380 +1G>A),
      and four deletions (c.715_717delGTC, p.V239del; c.304delA, p.N102DfsX4;
      c.1970_2177del, p.V657_G726; c.2113_2114delGG, p.G705RfsX16). Whereas we
      confirmed lack of direct correlation between the clinical phenotype and the
      genotype, we also found that the so-called 'common mutation' (p.R50X) accounted
      for about 43% of alleles in our cohort and that no population-related mutations
      are clearly identified in Italian patients.

PMID- 16786515
TI  - Novel and recurrent mutations in keratin KRT5 and KRT14 genes in epidermolysis
      bullosa simplex: implications for disease phenotype and keratin filament
      assembly.
AB  - Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant genetic skin
      disorders caused by mutations of the keratin genes KRT5 and KRT14. It is
      characterised by lysis of basal keratinocytes leading to the development of
      intraepidermal blisters upon minor mechanical trauma. We investigated 27 EBS
      patients and families of mainly German origin by sequence analysis of the entire
      coding sequences of KRT5 and KRT14 and identified 12 novel and seven previously
      reported mutations within the KRT5 and KRT14 genes. The study discusses possible
      implications of the novel mutations on protein structure, keratin intermediate
      filament (KIF) formation and the corresponding phenotype, and summarises the
      spectrum of mutations reported so far in EBS. Detailed knowledge of the spectrum
      of EBS mutations and their genotype-phenotype correlation is essential for
      accurate genetic counselling and prenatal diagnosis.

PMID- 16786516
TI  - Sub-Saharan African coding sequence variation and haplotype diversity at the NAT2
      gene.
AB  - A total of 530 chromosomes from 12 sub-Saharan African populations were sequenced
      at the human arylamine N-acetyltransferase NAT2 gene. We identified seven novel
      non-synonymous mutations observed at low frequencies (<11%) in our African multi
      ethnic panel. By using algorithms based on evolutionary conservation, two
      mutations (c.70T>A [p.L24I] and c.578C>T [p.T193M]) for which the activity of
      their encoded protein has never been determined, were predicted to entail a
      potentially damaging effect on protein activity. In addition, approximately 5% of
      the overall NAT2 African haplotypes presented an unknown functional effect. More
      interestingly, NAT2 haplotype frequencies and acetylation status inference
      revealed that the hunter-gatherer Western Pygmies and !Kung San were mainly
      composed of fast and intermediate acetylators, in clear contrast with most
      agriculturalist populations. These observations highlight the need of a detailed
      genetic characterization of African populations at this locus to adapt medical
      treatment, such as the antitubercular isoniazid, to individual/population make-up
      in the most effective manner.

PMID- 16786517
TI  - A common mutation in the CBS gene explains a high incidence of homocystinuria in
      the Qatari population.
AB  - We report the results of a study carried out to delineate genetic and
      epidemiological aspects of homocystinuria in the Qatari population. Sixty-four
      patients with homocystinuria (37 males, 27 females, age 1 to 29 years) from 31
      nuclear families were ascertained over a period of more than four years. The
      incidence of homocystinuria in Qatar was calculated to be > or =1:3000, the
      highest in the world known so far. All patients in whom data were available were
      vitamin B6-nonresponsive. Molecular studies were performed in all patients. All
      53 patients from tribe M and all three patients from tribe K were homozygous for
      the mutation c.1006C>T (p.R336C) in the CBS gene, with an additional seven
      patients resulting from mixed marriages between tribe M and tribe K. A single
      patient from tribe S was homozygous for mutation c.700G>A (p.D234N) in the CBS
      gene. Both mutations have been previously reported but involve hypermutable CpG
      dinculeotides and may be recurrent mutations in the Qatari population. The
      results of this study illustrate a strong founder effect causing a high
      prevalence of an autosomal recessive disease in a highly consanguineous Arabian
      population. Molecular neonatal screening may be suitable for early detection of
      homocystinuria in this population.

PMID- 16786518
TI  - Partner's behavior, not reward distribution, determines success in an unequal
      cooperative task in capuchin monkeys.
AB  - It was recently demonstrated that capuchin monkeys notice and respond to
      distributional inequity, a trait that has been proposed to support the evolution
      of cooperation in the human species. However, it is unknown how capuchins react
      to inequitable rewards in an unrestricted cooperative paradigm in which they may
      freely choose both whether to participate and, within the bounds of their
      partner's behavior, which reward they will receive for their participation. We
      tested capuchin monkeys with such a design, using a cooperative barpull, which
      has been used with great success in the past. Contrary to our expectations, the
      equity of the reward distribution did not affect success or pulling behavior.
      However, the behavior of the partner in an unequal situation did affect overall
      success rates: pairs that had a tendency to alternate which individual received
      the higher-value food in unequal reward situations were more than twice as
      successful in obtaining rewards than pairs in which one individual dominated the
      higher-value food. This ability to equitably distribute rewards in inherently
      biased cooperative situations has profound implications for activities such as
      group hunts, in which multiple individuals work together for a single,
      monopolizable reward.

PMID- 16786519
TI  - Intragroup lethal aggression in wild spider monkeys.
AB  - We report the first evidence of intragroup coalitionary aggression leading to the
      death of a wild young adult male spider monkey. During a long-term study of a
      well-habituated community at the Otoch Ma'ax Yetel Kooh reserve in Yucatan,
      Mexico, a young adult male sustained severe injuries repeatedly between January
      and March 2002. On 1 April 2002 the same male was the victim of an intragroup
      attack by at least one adult male that resulted in his death. We highlight
      several causes of intragroup aggression that may account for the killing.

PMID- 16786520
TI  - Bed-building in captive chimpanzees (Pan troglodytes): the importance of early
      rearing.
AB  - In the wild, great apes sleep in beds they make by successively bending branches
      into an interwoven platform. These beds are functionally more closely related to
      human beds than they are to the nests and tree-holes used by other primate
      species. The idea that bed-building by great apes is learned behavior that is
      dependent on appropriate early experiences has been proposed but never fully
      tested. In the present study this hypothesis was indirectly tested in 73 captive
      adult chimpanzees (Pan troglodytes; 27 wild-born and 46 captive-born). Bed
      building and use were tested experimentally by the introduction of three sets of
      bedding materials. Over 200 hr of scan-sampling data were collected during 45-min
      observations following introduction of the bedding material. The wild-born
      subjects built and used beds significantly more often than the captive-born
      subjects. Also, wild-born subjects used more complex techniques during
      construction. Captive-born subjects that were mother-reared through early
      adolescence spent more time building and using beds than their nursery-reared
      counterparts. These differences remained consistent even when previous adult
      experience with bedding (measured as naturalistic vs. traditional housing) was
      accounted for. These results suggest that bed-building is a learned behavior that
      requires early experience and practice for acquisition.

PMID- 16786521
TI  - Cross-genus adoption of a marmoset (Callithrix jacchus) by wild capuchin monkeys
      (Cebus libidinosus): case report.
AB  - We report a case of interspecies adoption of an infant marmoset (Callithrix
      jacchus) by wild capuchin monkeys (Cebus libidinosus). The marmoset was an infant
      when it was first observed in the capuchin group on 3 March 2004. Since it first
      appeared it has been observed informally and frequently. In January 2005
      systematic observations were made of the marmoset and a capuchin of similar age.
      Throughout its period of adoption the marmoset appeared to be socially integrated
      into the group, benefiting from nurturant behaviors exhibited by two successive
      adoptive "mothers" and pronounced tolerance from all members of the group. This
      case highlights the flexibility of both Callithrix and Cebus in accommodating
      variable social behaviors and other characteristics (including size) of social
      partners.

PMID- 16786522
TI  - What Hanuman langur males know about female reproductive status.
AB  - In species with a high risk of infanticide, a conflict of interest exists between
      the sexes over the amount of paternity information that is available to males.
      While females are expected to keep males unaware of their reproductive status in
      order to confuse paternity, selection should favor those male traits that enhance
      the males' assessment of female status and consequently of paternity probability.
      In Hanuman langurs (Semnopithecus entellus), a species that is extremely
      vulnerable to infanticide, females have been shown to successfully conceal the
      exact timing of ovulation from males--perhaps because they exhibit no sexual
      swelling and mate during all reproductive phases, including gestation.
      Nevertheless, it remains unclear whether males have hitherto unrecognized
      information about females' reproductive condition on a broader level that could
      still enhance male reproductive success. We investigated male assessment of
      female reproductive states in a population of wild Hanuman langurs as indicated
      by changes in male behavior, such as rates of copulations, anogenital
      inspections, and consortships, in relation to different female receptive periods
      (pregnant, fertile-nonconceptional, and conceptional). Our data indicate that
      males were able to discern qualitatively distinct reproductive states. Males were
      more interested in fertile than pregnant females, as indicated by higher
      copulation rates. Based on consortships, males distinguished fertile from
      nonfertile phases, as well as fertile, nonconceptional receptive periods from
      conceptional ones. Hanuman langur males are thus not as unaware of female
      reproductive condition as previously thought, supporting the idea of an ongoing
      battle of the sexes over paternity information. However, granting some knowledge
      while at the same time concealing the exact day of ovulation may also reflect a
      pure female strategy of balancing paternity concentration with paternity
      confusion, which is the most likely strategy in this system with high infanticide
      risk and male defense of infants.

PMID- 16786523
TI  - Tetanus antibody titers and duration of immunity to clinical tetanus infections
      in free-ranging rhesus monkeys (Macaca mulatta).
AB  - Prior to 1985 tetanus was a major cause of mortality in the free-ranging colony
      of rhesus monkeys on Cayo Santiago, accounting for almost a quarter of annual
      deaths. In 1985 and 1986 all animals (except infants) received primary and
      booster doses, respectively, of tetanus toxoid. In subsequent years primary
      immunizations were given to all yearlings, and boosters were administered to all
      2-year-old animals during the annual capture of the colony. The main objectives
      of the tetanus immunization program were to reduce the pain and suffering caused
      by tetanus infections and to decrease mortality in the colony. Other objectives
      were to evaluate the efficacy of the two-dose tetanus toxoid immunization
      protocol and to determine whether additional boosters might be required to
      provide adequate long-term protection against tetanus infections. The immediate
      effect of the mass immunization program was the elimination of clinical tetanus
      infections in the population and a 42.2% reduction in the overall mortality rate.
      Since the immunization program began, no cases of tetanus have been observed in
      the colony, except in two unimmunized infants, and it has not been necessary to
      give tertiary injections of tetanus toxoid to maintain protection against
      infection. A sample collected in 2004 of the original cohort of monkeys immunized
      in 1985 and 1986 showed that 93.3% (14/15) had protective tetanus antibody titers
      (>0.01 IU/ml) at the ages of 20-23 years, which is close to the life expectancy
      of the Cayo Santiago rhesus macaques. Two intramuscular doses of tetanus toxoid
      provided long-term, if not lifelong, protection against tetanus for rhesus
      monkeys living in a tropical clime where tetanus is enzootic and the risk of
      infection is great.

PMID- 16786524
TI  - Selective attention toward female secondary sexual color in male rhesus macaques.
AB  - Pink-to-red anogenital and facial sexual skin occurs in females of many primate
      species. Since female sexual skin color varies with reproductive state, it has
      long been assumed that color acts to stimulate male sexual interest. Although
      there is supportive evidence for this as regards anogenital skin, it is unclear
      whether this is also the case for facial sexual skin. In this study we
      experimentally manipulated digital facial and hindquarter images of female rhesus
      macaques (Macaca mulatta) for color within the natural range of variation. The
      images were presented to adult male conspecifics to assess whether the males
      exhibited visual preferences for red vs. non-red female coloration, and whether
      preferences varied with anatomical region. The males displayed significantly
      longer gaze durations in response to reddened versions of female hindquarters,
      but not to reddened versions of faces. This suggests that female facial
      coloration may serve an alternative purpose to that of attracting males, and that
      the signal function of sexual skin and the intended recipients may vary across
      anatomical regions.

PMID- 16786526
TI  - Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study.
AB  - OBJECTIVE: To evaluate the relation between T2 lesions and disease severity in
      relapsing-remitting multiple sclerosis (MS). METHODS: This article describes a 13
      year longitudinal study in 30 patients. RESULTS: Patients were 36.3 +/- 6.0 years
      old, had MS for 6.1 +/- 5.8 years, Expanded Disability Status Scale was 2.2 +/-
      0.8, and brain parenchymal fraction (BPF) was 0.825 +/- 0.015 at study entry. At
      last visit, Expanded Disability Status Scale was 4.4 +/- 1.95, Multiple Sclerosis
      Functional Composite was -0.34 +/- 1.7, and BPF was 0.774 +/- 0.037. Baseline T2
      lesion volume correlated with the BPF of the last visit (r = -0.66; p < 0.0001),
      magnetization transfer ratio (MTR) in normal-appearing brain tissue (r = -0.52; p
      = 0.004), and lesion MTR (r = -0.76; p < 0.0001). Change in T2 lesion volume in
      the first 2 years correlated with BPF of the last visit (r = -0.40; p = 0.03),
      normal-appearing brain tissue MTR (r = -0.44; p = 0.015), lesion MTR (r = -0.46;
      p = 0.018), Multiple Sclerosis Functional Composite scores (r = -0.50; p =
      0.005), and Paced Auditory Serial Addition Task scores (r = -0.52; p = 0.003).
      Age was a significant covariate for clinical but not magnetic resonance imaging
      outcomes. INTERPRETATION: T2 lesions in relapsing-remitting MS correlate strongly
      with brain tissue loss and brain tissue integrity 13 years later, and with
      clinical disease severity, though age significantly impacts the clinical
      correlation. The results provide direct evidence for the disability threshold
      hypothesis in MS and support monitoring T2 lesions in relapsing-remitting MS.

PMID- 16786525
TI  - Cold extends electromyography distinction between ion channel mutations causing
      myotonia.
AB  - OBJECTIVE: Myotonias are inherited disorders of the skeletal muscle excitability.
      Nondystrophic forms are caused by mutations in genes coding for the muscle
      chloride or sodium channel. Myotonia is either relieved or worsened by repeated
      exercise and can merge into flaccid weakness during exposure to cold, according
      to causal mutations. We designed an easy electromyography (EMG) protocol
      combining repeated short exercise and cold as provocative tests to discriminate
      groups of mutations. METHODS: Surface-recorded compound muscle action potential
      was used to monitor muscle electrical activity. The protocol was applied on 31
      unaffected control subjects and on a large population of 54 patients with
      chloride or sodium channel mutations known to cause the different forms of
      myotonia. RESULTS: In patients, repeated short exercise test at room temperature
      disclosed three distinct abnormal patterns of compound muscle action potential
      changes (I-III), which matched the clinical symptoms. Combining repeated exercise
      with cold exposure clarified the EMG patterns in a way that enabled a clear
      correlation between the electrophysiological and genetic defects. INTERPRETATION:
      We hypothesize that segregation of mutations into the different EMG patterns
      depended on the underlying pathophysiological mechanisms. Results allow us to
      suggest EMG guidelines for the molecular diagnosis, which can be used in clinical
      practice.

PMID- 16786527
TI  - Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis.
AB  - OBJECTIVE: The objective of this study was to identify the gene causing autosomal
      recessive infantile bilateral striatal necrosis. METHODS: We have mapped the
      disease gene in the candidate region to approximately 230kb on 19q13.33 in 8
      interrelated families including a total of 12 patients and 39 unaffected
      individuals. RESULTS: Sequencing of the nup62 gene showed a missense mutation
      causing a change from glutamine to proline (Q391P) in all the patients, producing
      a substitution from a polar, hydrophilic residue to a nonpolar, neutral residue.
      All the other 12 candidate genes were sequenced, and no pathogenic sequence
      changes were found. Comparisons of p62 protein sequences from diverse species
      indicate that glutamine at position 391 is highly conserved. Five prenatal
      diagnoses were performed in three at-risk families. INTERPRETATION: This is the
      second example of a nuclear pore complex protein causing mendelian disease in
      humans (the first one is triple A syndrome). Our findings suggest that p62 has a
      cell type-specific role and is important in the degeneration of the basal ganglia
      in humans.

PMID- 16786529
TI  - Choline acetyl transferase and neuropeptide immunoreactivities are colocalized in
      somata, but preferentially localized in distinct axon fibers and boutons of cat
      sympathetic preganglionic neurons.
AB  - Cholinergic sympathetic preganglionic neurons (SPN) coexpress the biosynthetic
      enzyme for acetylcholine, choline acetyl-transferase (ChAT), and neuropeptides
      such as enkephalin (ENK) in their cell bodies. However, it is not clear whether
      they also coexpress ChAT and neuropeptides in axon fibers and boutons. To explore
      coexpression of ChAT and neuropeptides in somata and axon processes of SPN, we
      investigated, using immunohistochemistry, retrograde labeling, confocal analysis,
      and tridimensional reconstruction, whether ChAT and the peptides neurotensin,
      methionine-ENK, somatostatin, calcitonin gene-related peptide, and vasoactive
      intestinal peptide colocalize in somata, axons fibers, and boutons of cat SPN.
      Practically, complete colocalization for these peptides and ChAT was observed in
      SPN somata. Conversely, in most instances we observed independent localization of
      immunoreactivity (IR) for ChAT and the peptides in axon fibers and boutons. The
      minor colocalization between ChAT- and peptide-IR in preganglionic fibers could
      correspond to a sequential axonal transport of ChAT and peptides, since we
      observed coexistence of these transmitters after blocking axonal transport.
      Contrary to Dale's principle, our results suggest that SPN can synthesize ChAT
      and peptides in their cell bodies and route them to distinct axon boutons or
      terminals in sympathetic ganglia. Presence of axon boutons containing either ChAT
      or neuropeptides lead us to suggest a new neurochemical pattern of cotransmission
      in sympathetic ganglia based on the concurrent release of transmitters and
      cotransmitters from distinct presynaptic boutons, rather than in the corelease of
      these mediators from the same axon process. The possibility that cellular
      segregation could be transient and depend on functional requirements is
      considered.

PMID- 16786528
TI  - Dopamine receptor signaling molecules are altered in elderly schizophrenic
      cortex.
AB  - Alterations of molecules that mediate dopaminergic signal transduction have been
      found in schizophrenia, supporting the hypothesis of altered dopaminergic
      neurotransmission in this illness. To further explore this hypothesis, the
      authors measured transcript expression of three proteins involved in dopamine
      (DA) signaling in postmortem dorsolateral prefrontal and anterior cingulate
      cortex of elderly schizophrenic subjects and a comparison group. The transcript
      encoding calcyon, a protein that potentiates crosstalk between D1 DA receptors
      and Gq/11-linked receptors, was increased in schizophrenic prefrontal and
      cingulate cortex by 25%. Transcript levels of spinophilin, a protein enriched in
      dendritic spines that modulates excitatory neurotransmission, were increased 22%
      in dorsolateral prefrontal cortex but were unchanged in anterior cingulate cortex
      in schizophrenia. Levels of DARPP-32 mRNA, a downstream effector of dopaminergic
      neurotransmission, were similar in both groups for both cortical groups. These
      alterations in spinophilin and calcyon mRNA levels in schizophrenic prefrontal
      and cingulate cortex provide further evidence of altered dopaminergic
      neurotransmission in this illness.

PMID- 16786530
TI  - Prefrontal infusion of PD098059 immediately after fear extinction training blocks
      extinction-associated prefrontal synaptic plasticity and decreases prefrontal
      ERK2 phosphorylation.
AB  - A previous study has demonstrated that disruption of fear extinction-induced long
      term potentiation (LTP) in the medial prefrontal cortex (mPFC) is associated with
      the return of fear responding. Given that immediate posttraining infusion of
      PD098059, an inhibitor of extracellular signal-regulated kinase (ERK) mitogen
      activated protein kinase (MAPK) cascade, into the mPFC also promotes recovery of
      fear, we investigated whether impairment of mPFC ERK/MAPK cascade also interferes
      with development of extinction-related LTP in the mPFC in rats. In Experiment 1,
      extinction training consisting of repetitive presentations of a tone previously
      associated with eyelid-shock application induced LTP-like changes at hippocampal
      inputs to the mPFC that were evident for approximately 2 h following fear
      extinction. Infusion of PD098059 into the mPFC immediately after extinction
      training abolished training-related prefrontal LTP and impaired retention of
      extinction memory tested on the following day. In Experiment 2, immunoblotting
      assays revealed that posttraining infusion of PD098059 into the mPFC produced a
      significant reduction of mPFC ERK2. These data, along with previous findings,
      suggest that low levels of ERK2 phosphorylation in the mPFC may interfere with
      mechanisms of retention of extinction training. The involvement of mPFC LTP in
      fear extinction is discussed.

PMID- 16786531
TI  - Detection of 95 novel mutations in coagulation factor VIII gene F8 responsible
      for hemophilia A: results from a single institution.
AB  - Hemophilia A (HA) is an X-linked hereditary bleeding disorder defined by a
      qualitative and/or quantitative factor VIII (FVIII) deficiency. The molecular
      diagnosis of HA is challenging because of the high number of different causative
      mutations that are distributed throughout the large F8 gene. The putative role of
      the novel mutations, especially missense mutations, may be difficult to interpret
      as causing HA. We identified 95 novel mutations out of 180 different mutations
      responsible for HA in 515 patients from 406 unrelated families followed up at a
      single hemophilia treatment center of the Bicetre university hospital (Assistance
      Publique-Hopitaux de Paris [AP-HP], Le Kremlin-Bicetre). These 95 novel mutations
      comprised 55 missense mutations, 12 nonsense mutations, 11 splice site mutations,
      and 17 small insertions/deletions. We therefore developed a mutation analysis
      based on a body of proof that combines the familial segregation of the mutation,
      the resulting biological and clinical HA phenotype, and the molecular
      consequences of the amino acid (AA) substitution. For the latter, we studied the
      putative biochemical modifications: its conservation status with cross-species
      FVIII and homologous proteins, its putative location in known FVIII functional
      regions, and its spatial position in the available FVIII 3D structures. The
      usefulness of such a strategy in interpreting the causality of novel F8 mutations
      is emphasized.

PMID- 16786532
TI  - In vitro analysis of genomic instability triggered by BRCA1 missense mutations.
AB  - The BRCA1 tumor suppressor gene encodes a phosphoprotein involved in many
      cellular key functions including DNA repair, transcription regulation, cell-cycle
      control and apoptosis. Most of these functions are strictly related to the
      ability of BRCA1 to interact with the other partners of a multimeric complex
      called BASC. Among these components, an important role is played by the human
      homolog of the bacterial MutL, MLH1. In this study, we have identified the BRCA1
      binding domains to MLH1 and demonstrated that three distinct mutations in one of
      these interaction domains can produce, in vitro, a microsatellite instability
      phenotype, one of the hallmarks of an imbalance in the mismatch DNA repair
      machinery. These data support a model in which a structural modification in a
      critical domain of the BRCA1 gene product secondary to single amino acid
      mutations, may be able, per se, to impair the DNA damage response pathway,
      inducing genomic instability and eventually leading to breast carcinogenesis.

PMID- 16786533
TI  - Mutational spectrum of maple syrup urine disease in Spain.
AB  - Mutations in any of the three different genes BCKDHA, BCKDHB, and DBT encoding
      for the E1alpha, E1beta, and E2 catalytic components of the branched-chain alpha
      ketoacid dehydrogenase (BCKD) complex can cause maple syrup urine disease (MSUD).
      The disease presents heterogeneous clinical and molecular phenotypes. Severity of
      the disease ranges from the classical to the mildest variant types. Here, we
      describe the MSUD genotypes and related phenotypes in a cohort of 33 Spanish
      patients. Based on complementation testing, we selected 15 patients as defective
      in E1beta, 10 in E1alpha, seven in E2l; one remains unclassified. 92.5% of
      alleles have been characterized, and the mutational spectrum includes 36
      different sequence variations presumably leading to loss-of-function, 15 changes
      in the BCKDHA, 14 in the BCKDHB, and seven in the DBT genes. Twenty-four changes
      are novel. The mutational profile is heterogeneous with no prevalent sequence
      variations detected, except for the E1beta mutation, c.487G>T (p.Glu163X), which
      appears on six out of 30 disease alleles analyzed. Approximately 30% of the
      patients included in this study showed a variant MSUD phenotype. That included
      50% of the patients identified as EIa and at least four out of seven of those
      selected as EII. Precise genotypes as c.[647C>T]+[889C>T] for the EIa and
      c.[827T>G ]+[1349C>A] for the EII appeared associated to the mildest
      presentations of the disease.

PMID- 16786534
TI  - Variability of pesticide residues in crop units.
AB  - The results of 89 new field trials and 11 supervised trials were considered,
      together with 91 sets of residue data evaluated earlier. The datasets consisted
      of 22,643 valid residue data. As all variability factors calculated from
      individual sample sets are affected by the uncertainties of sampling and
      analysis, the average of the P(0.975)/R(ave) (97.5th percentile of the residue
      population divided by the average residues in the lot) values gives the best
      estimate for the variability factor. The Harrell-Davis (H-D) method gave an
      average value of 2.89 for the variability factor for all samples, while the
      average variability factors obtained from samples derived from the new field and
      supervised trials were 2.8 and 2.7 with the IUPAC and H-D methods respectively.
      The number of residue values below the LOQ in a sample set significantly affects
      the observed variability factors. It was found that datasets containing over 20%
      non-quantifiable residues might not reflect the true variability of the residues.
      Mixing of treated and non-treated commodities may significantly increase the
      apparent variability. Consequently, only datasets of known origin and consisting
      of well-quantifiable residues should be used for estimation of the variability
      factor. Samples taken from marketed lots may not represent a single lot, and thus
      they have limited value in estimating the variability factor. The large number of
      residue data confirms the applicability of the default variability factor of 3
      adopted by the FAO/WHO for deterministic estimation of the acute intake of
      pesticide residues.

PMID- 16786535
TI  - Methylthioadenosine reverses brain autoimmune disease.
AB  - OBJECTIVE: To assess the immunomodulatory activity of methylthioadenosine (MTA)
      in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with
      multiple sclerosis. METHODS: We studied the effect of intraperitoneal MTA in the
      acute and chronic EAE model by quantifying clinical and histological scores and
      by performing immunohistochemistry stains of the brain. We studied the
      immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral
      blood mononuclear cells from healthy control subjects and multiple sclerosis
      patients by assessing cell proliferation and cytokine gene expression, by real
      time polymerase chain reaction, and by nuclear factor-kappaB modulation by
      Western blot. RESULTS: We found that MTA prevents acute EAE and, more
      importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited
      brain inflammation and reduced brain damage. Administration of MTA suppressed T
      cell activation in vivo and in vitro, likely through a blockade in T-cell
      signaling resulting in the prevention of inhibitor of kappa B (IkappaB-alpha)
      degradation and in the impaired activation transcription factor nuclear factor
      kappaB. Indeed, MTA suppressed the production of proinflammatory genes and
      cytokines (interferon-gamma, tumor necrosis factor-alpha, and inducible nitric
      oxide synthase) and increased the production of antiinflammatory cytokines
      (interleukin-10). INTERPRETATION: MTA has a remarkable immunomodulatory activity
      and may be beneficial for multiple sclerosis and other autoimmune diseases.

PMID- 16786537
TI  - Amyloid beta-protein fragment 31-35 suppresses long-term potentiation in
      hippocampal CA1 region of rats in vivo.
AB  - Effects of fragment 31-35 of amyloid beta-protein (AbetaP31-35) on the baseline
      synaptic transmission, shown as fEPSPs, and the long-term potentiation (LTP)
      induced by high-frequency stimuli (HFS) were investigated in vivo in the
      hippocampal CA1 region of rats; a longer fragment of AbetaP, i.e., AbetaP25-35,
      which had been generally accepted as the active center in AbetaP, was also tested
      comparatively along with AbetaP31-35. The results showed that: (1) the baseline
      fEPSPs induced by test stimuli were not changed by i.c.v. injection of AbetaP31
      35, while application of either AbetaP31-35 or AbetaP25-35 with the same molar
      concentration (50 nmol) significantly and similarly suppressed the HFS-induced
      LTP; (2) higher concentration of AbetaP31-35 or longer time of AbetaP exposure
      exhibited stronger suppression on LTP, indicating a dose- and time-dependent
      trends; (3) no significant effects could be found on the paired-pulse
      facilitation (PPF) following AbetaP31-35 injection; (4) pretreatment with
      verapamil (2.5 mg/kg, i.p., 1 h prior to HFS), a blocker of L-type Ca2+ channels,
      did not affect the baseline fEPSPs, while it exhibited a significant suppression
      on LTP induced by HFS; and (5) surprisingly enough, coapplication with verapamil
      and AbetaP31-35 exhibited a similar suppression on LTP just as both of these two
      agents were used alone. These results indicate that: (1) AbetaP31-35, similar to
      AbetaP25-35, possesses potent suppressive effects on hippocampal LTP in vivo,
      supporting our proposal that the fragment AbetaP31-35 might be to date the
      shortest active sequence in full-length of AbetaP molecule; (2) AbetaP31-35
      induced LTP suppression is not mediated by affecting the presynaptic processes;
      and (3) L-type Ca2+ channels might be one of the main pathways by which AbetaP31
      35 insults LTP.

PMID- 16786536
TI  - No role of the dopamine transporter in acute ethanol effects on striatal dopamine
      dynamics.
AB  - The acute effects of ethanol on dopamine (DA) release and clearance in the
      caudate-putamen were evaluated in wild-type and dopamine transporter (DAT)
      knockout (DAT-KO) mice, using microdialysis and voltammetry. Dialysate DA levels
      were elevated, approximately 80% above baseline levels, after administration of 2
      g/kg ethanol in both wild-type and DAT-KO mice. In brain slices containing the
      caudate-putamen, a low (20 mM) concentration of ethanol produced no change in
      electrically stimulated DA release in either wild-type or DAT-KO mice. A high
      concentration (200 mM) of ethanol caused a similar decrease in DA release in
      slices from both types of mice. DA clearance was unaltered across the genotypes
      at low and high concentrations of ethanol. The fact that ethanol had similar
      effects in wild-type and DAT-KO mice, measured by in vivo microdialysis or brain
      slice voltammetry, supports the idea that acute ethanol does not interact with
      the DAT to produce its effects on the DA system.

PMID- 16786538
TI  - Radiosynthesis, ex vivo and in vivo evaluation of [11C]preclamol as a partial
      dopamine D2 agonist radioligand for positron emission tomography.
AB  - Dopamine D2 partial agonists have been successfully used as schizophrenia
      therapeutics. Radiolabeled D2 partial agonists may have application in
      elucidating dopaminergic transmission. It was the goal of this work to radiolabel
      (S)-(-)propyl-3-(3-hydroxyphenyl)piperidine (preclamol; (-)3-PPP), a partial
      dopamine D2 agonist with carbon-11 (half-life=20.4 min) and to evaluate this
      novel radiopharmaceutical for dopaminergic imaging in rodent models.
      [11C]Preclamol was synthesized by acylation of (S)-3-(3-hydroxyphenyl)piperidine
      hydrochloride with [11C]propionyl chloride, followed by LiAlH4 reduction, and
      HPLC purification. Male Sprague-Dawley rats were injected in the tail vein with a
      saline solution of [11C]preclamol (1.1 mug/kg) and sacrificed at 5, 15, 30 and 60
      min postinjection. Brain regions were excised, weighed, and measured for
      radioactivity. In vivo binding kinetics of [11C]preclamol were determined with
      beta-sensitive microprobes implanted into the striatum and cerebellum of an
      anesthetized rat. A full production of [11C]preclamol resulted in 34 mCi ready
      for injection (corresponding to 4% uncorrected radiochemical yield, based on
      starting [11C]CO2) with specific activity of 535 mCi/micromol. The total
      synthesis time was 45 min and resulted in chemically and radiochemically pure
      [11C]preclamol (>99%; n=3). High levels of radioactivity were observed in rat
      brain indicating good blood-brain barrier penetration of [11C]preclamol, with 0.5
      to 0.7% injected dose per gram of wet tissue present in all brain regions at 5
      minutes postinjection. Unfortunately, [11C]preclamol displayed minimal
      preferential uptake in dopaminergic brain regions. A low striatal specific
      binding (SB) ratio of 0.32 was determined ex vivo at 60 min postinjection and was
      in close agreement with the microprobe study over 60 min (peaked at 27 min
      postinjection; SB ratio=0.6). The binding potential value was only 0.34 over a 1
      hour time course, suggesting that [11C]preclamol is not suitable for cerebral PET
      studies.

PMID- 16786539
TI  - Control of Aspergillus growth and aflatoxin production using natural maize
      phytochemicals under different conditions of water activity.
AB  - The effects of the natural phytochemicals trans-cinnamic acid (CA) and ferulic
      acid (FA) alone at concentrations of 1-25 mM and in 16 combinations (M: mixtures)
      on growth and aflatoxin B(1) production by Aspergillus flavus Link and A.
      parasiticus Speare were evaluated. Studies on growth rate and aflatoxin B(1)
      production were carried out in vitro in relation to a water activity a(w) of
      0.999, 0.971, 0.955 and 0.937. Overall, CA at concentrations of 10 and 20 mM and
      FA-CA mixtures M3 (20 + 5 mM respectively), M8 (25 + 5 mM), M9 (1 + 10 mM), M10
      (10 + 10 mM), M11 (20 + 10 mM), M12 (25 + 10 mM), M13 (1 + 20 mM), M14 (10 + 20
      mM), M15 (20 + 20 mM) and M16 (25 + 20 mM) were the treatments most effective at
      inhibiting growth of the four species assayed. All strains were much more
      sensitive to all natural phytochemicals tested on growth rate at a(w) = 0.937. CA
      and the FA-CA mixtures M1 (1 + 1 mM respectively), M4 (25 + 1 mM), M5 (1 + 5 mM),
      M6 (10 + 1 mM), M7 (20 + 1 mM), M8 (25 + 5 mM), M9 (1 + 10 mM), M10 (10 + 10 mM),
      M11 (20 + 10 mM), M12 (25 + 10 mM), M13 (1 + 20 mM), M14 (10 + 20 mM), M15 (20 +
      20 mM) and M16 (25 + 20 mM) completely inhibited aflatoxin B(1) production by all
      strains at a(w) = 0.999, 0.971, 0.955 and 0.937. Decreased aflatoxin B(1) levels
      in comparison with the control were observed with FA at 1, 10, 20 and 25 mM with
      the strains RCM89, RCM108 and RCM38 at a(w) = 0.971, 0.955 and 0.999
      respectively. The data show that CA and FA can be considered as effective
      fungitoxicants for A. flavus and A. parasiticus in in vitro assay. The
      information obtained is part of an ongoing study to determine their application
      at the storage level.

PMID- 16786540
TI  - Toxicity of spray and fumigant products containing cassia oil to Dermatophagoides
      farinae and Dermatophagoides pteronyssinus (Acari: Pyroglyphidae).
AB  - The toxicity of formulations of oil of cassia, Cinnamomum cassia Blume, (20 and
      50 g L(-1) sprays and 100% oil-based fumigant) to adult Dermatophagoides farinae
      Hughes and D. pteronyssinus Trouessart was examined using contact and vapour
      phase toxicity bioassays. Results were compared with the lethal activity of three
      commercial acaricides: benzyl benzoate, dibutyl phthalate and diethyl-m-toluamide
      (deet). The contact toxicity of cassia oil to both dust mite species was
      comparable with that of benzyl benzoate but was higher than that of the other two
      acaricides. Sprays containing 20 and 50 g L(-1) cassia oil were effective against
      both mite species when applied to fabric, glass, paper, plastic, tin or wood
      substrates. Applications of the 50 g L(-1) spray to different space volumes and
      surface areas determined that 50-60 mg of cassia oil was needed to control dust
      mites in 3.4 m(3) or in 1 m(2). In tests with fumigant devices, toxicity varied
      according to the thickness of non-woven fabric covering the device, the exposure
      time, the number of fumigant devices used and the volume of the space sprayed.
      Fumigant toxicity to adult D. pteronyssinus was more pronounced with devices
      enclosed in thinner (40 microm) versus thicker (45 or 50 microm) non-woven fabric
      covers. A single fumigant device with a 40 microm thick non-woven fabric cover
      resulted in substantial control in a space of 0.05 m(3) but exhibited only
      moderate to weak control in spaces >or= 0.097 m(3) at 4 days after application.
      Two fumigant devices gave 88% mortality in a space of 1.73 m(3). Cassia oil
      applied as sprays or in fumigant devices appears to provide effective protection
      of humans from house dust mites.

PMID- 16786541
TI  - DFT models for copper(II) bispidine complexes: structures, stabilities,
      isomerism, spin distribution, and spectroscopy.
AB  - Various DFT and ab initio methods, including B3LYP, HF, SORCI, and LF-density
      functional theory (DFT), are used to compute the structures, relative
      stabilities, spin density distributions, and spectroscopic properties (electronic
      and EPR) of the two possible isomers of the copper(II) complexes with derivatives
      of a rigid tetradentate bispidine ligand with two pyridine and two tertiary amine
      donors, and a chloride ion. The description of the bonding (covalency of the
      copper-ligand interactions) and the distribution of the unpaired electron
      strongly depend on the DFT functional used, specifically on the nonlocal DF
      correlation and the HF exchange. Various methods may be used to optimize the DFT
      method. Unfortunately, it appears that there is no general method for the
      accurate computation of copper(II) complexes, and the choice of method depends on
      the type of ligands and the structural type of the chromophore. Also, it appears
      that the choice of method strongly depends on the problem to be solved. LF-DFT
      and spectroscopically oriented CI methods (SORCI), provided a large enough
      reference space is chosen, yield accurate spectroscopic parameters; EDA may lead
      to a good understanding of relative stabilities; accurate spin density
      distributions are obtained by modification of the nuclear charge on copper;
      solvation models are needed for the accurate prediction of isomer distributions.

PMID- 16786542
TI  - Theoretical, spectroscopic, and mechanistic studies on transition-metal
      dinitrogen complexes: implications to reactivity and relevance to the nitrogenase
      problem.
AB  - Dinitrogen complexes of transition metals exhibit different binding geometries of
      N2 (end-on terminal, end-on bridging, side-on bridging, side-on end-on bridging),
      which are investigated by spectroscopy and DFT calculations, analyzing their
      electronic structure and reactivity. For comparison, a bis(mu-nitrido) complex,
      where the N--N bond has been split, has been studied as well. Most of these
      systems are highly covalent, and have strong metal-nitrogen bonds. In the present
      review, particular emphasis is put on a consideration of the activation of the
      coordinated dinitrogen ligand, making it susceptible to protonation, reactions
      with electrophiles or cleavage. In this context, theoretical, structural, and
      spectroscopic data giving informations on the amount of charge on the N2 unit are
      presented. The orbital interactions leading to a charge transfer from the metals
      to the dinitrogen ligand and the charge distribution within the coordinated N2
      group are analyzed. Correlations between the binding mode and the observed
      reactivity of N2 are discussed.

PMID- 16786543
TI  - Can the semiempirical PM3 scheme describe iron-containing bioinorganic molecules?
AB  - A set of iron parameters for use in the semiempirical PM3 method have been
      developed to allow the structure and redox properties of the active sites of iron
      containing proteins to be accurately modeled, focussing on iron-sulfur, iron
      heme, and iron-only hydrogenases. Data computed at the B3LYP/6-31G* level for a
      training set of 60 representative complexes have been employed. A gradient-based
      optimization algorithm has been used, and important modifications of the core
      repulsion function have been highlighted. The derived parameters lead in general
      to good predictions of the structure and energetics of molecules both within and
      outside the training set, and overcome the extensive deficiencies of a B3LYP/STO
      3G model. Particularly encouraging is the success of the parameters in describing
      [4Fe-4S] cubanes. The derived parameter set provides a starting point should
      greater accuracy for a more restricted range of compounds be required.

PMID- 16786544
TI  - Laboratory and field tests of spray-dried and granular formulations of a Bacillus
      thuringiensis strain with insecticidal activity against the sugarcane borer.
AB  - Formulations of Bacillus thuringiensis Berliner (Bt) with insecticidal activity
      against the sugarcane borer, Diatraea saccharalis Fabricius (Lepidoptera:
      Pyralidae), were developed and tested under laboratory and field conditions. The
      formulations were prepared using biodegradable polymers such as modified corn
      starch as an encapsulating agent, gelatin as an adherent, powdered sugarcane as a
      feeding stimulant and a Bt var. kurstaki GM-34 strain from a non-sugarcane region
      as the active ingredient. The spore-crystal complex of this strain was mixed at
      three different concentrations (30, 70 and 100 g kg(-1)) with the other
      ingredients. The blends were prepared as spray-dried and granular formulations,
      and then submitted to laboratory tests with two day old larvae of D. saccharalis
      and field tests in sugarcane crops with natural sugarcane borer infestation.
      Spray-dried formulations in laboratory bioassays caused mortality near 100% with
      all three concentrations, and granular formulations caused mortality around 84%.
      The field tests showed that spray-dried formulations at 70 and 100 g kg(-1)
      concentrations were as effective as a commercial bioinsectide (Lepinox), while
      granular formulations were ineffective.

PMID- 16786545
TI  - Integrated pest management (IPM): definition, historical development and
      implementation, and the other IPM.

PMID- 16786546
TI  - DFT calculations of 57Fe Mossbauer isomer shifts and quadrupole splittings for
      iron complexes in polar dielectric media: applications to methane monooxygenase
      and ribonucleotide reductase.
AB  - To predict the isomer shifts of Fe complexes in different oxidation and spin
      states more accurately, we have performed linear regression between the measured
      isomer shifts (delta(exp)) and DFT (PW91 potential with all-electron triple-zeta
      plus polarization basis sets) calculated electron densities at Fe nuclei [rho(0)]
      for the Fe(2+,2.5+) and Fe(2.5+,3+,3.5+,4+) complexes separately. The geometries
      and electronic structures of all complexes in the training sets are optimized
      within the conductor like screening (COSMO) solvation model. Based on the linear
      correlation equation delta(exp) = alpha[rho(0) - 11884.0] + C, the best fitting
      for 17 Fe(2+,2.5+) complexes (totally 31 Fe sites) yields alpha = -0.405 +/-
      0.042 and C = 0.735 +/- 0.047 mm s(-1). The correlation coefficient is r = -0.876
      with a standard deviation of SD = 0.075 mm s(-1). In contrast, the linear fitting
      for 19 Fe(2.5+,3+,3.5+,4+) complexes (totally 30 Fe sites) yields alpha = -0.393
      +/- 0.030 and C = 0.435 +/- 0.014 mm s(-1), with the correlation coefficient r = 
      0.929 and a standard deviation SD = 0.077 mm s(-1). We provide a physical
      rationale for separating the Fe(2+,2.5+) fit from the Fe(2.5+,3+,3.5+,4+) fit,
      which also is clearly justified on a statistical empirical basis. Quadrupole
      splittings have also been calculated for these systems. The correlation between
      the calculated (DeltaE(Q(cal))) and experimental (DeltaE(Q(exp))) quadrupole
      splittings based on |DeltaE(Q(exp))| = A |DeltaE(Q(cal))| + B yields slope A,
      which is almost the ideal value 1.0 (A = 1.002 +/- 0.030) and intercept B almost
      zero (B = 0.033 +/- 0.068 mm s(-1)). Further calculations on the reduced
      diferrous and oxidized diferric active sites of class-I ribonucleotide reductase
      (RNR) and the hydroxylase component of methane monooxygenase (MMOH), and on a
      mixed-valent [(tpb)Fe3+(mu-O)(mu-CH3CO2)Fe4+(Me3[9]aneN3)]2+ (S = 3/2) complex
      and its corresponding diferric state have been performed. Calculated results are
      in very good agreement with the experimental data.

PMID- 16786547
TI  - A theoretical framework for TTO valuations of health.
AB  - This paper proposes a theoretical framework, drawing on Hicks utility theory, for
      the Time Trade-off (TTO) method conventionally used to value health states. We
      briefly describe that theory and posit four distinctive TTO valuation approaches
      suggested by it: each of compensating variation and equivalent variation for both
      gains and losses in health, with valuation of health states in each case derived
      from trade-offs between health and length of life. Recent developments and
      research on TTO valuation are placed in the context of this framework.

PMID- 16786548
TI  - The impact of prenatal care on birthweight: the case of Uruguay.
AB  - This study analyzes prenatal care and birthweight in Uruguay. These data are
      unique since they represent a population of urban, poor women who gave birth in a
      health care system that provides both prenatal and obstetric care free of charge.
      This study finds a positive effect of increased prenatal care use on birthweight
      and evidence of bias in OLS estimates, similar to studies that use US data. The
      results highlight the usefulness of existing methodologies for estimating the
      effect of prenatal care on birthweight and the importance of extending these
      methodologies to data from countries other than the US.

PMID- 16786549
TI  - The Dutch tariff: results and arguments for an effective design for national EQ
      5D valuation studies.
AB  - The objective of this study was to estimate a Dutch EQ-5D tariff and to determine
      in a simulation study using the dataset of the original UK valuation study, the
      number of health states and respondents needed to estimate a reliable tariff. In
      all, 300 Dutch respondents directly valued 17 states compared to 3000 respondents
      and 42 states in the original MVH protocol. The results reaffirmed differences in
      health-related preferences between countries, justifying the estimation of
      national tariffs. The mean absolute error was 0.030. The design of this study is
      recommended for national EQ-5D valuation studies.

PMID- 16786550
TI  - Ordering effect and price sensitivity in discrete choice experiments: need we
      worry?
AB  - The objective of this paper is to analyse the impact that attribute ordering has
      on the relative importance of the price attribute. A discrete choice experiment
      was performed in order to elicit psoriasis patients' preferences for treatment.
      We tested for ordering effect with respect to the price attribute, and disclosed
      noticeable higher price sensitivity when the price attribute was placed at the
      end of the program description. Our results indicate that preferences are context
      dependent and that heuristics may be used in the choice process. Our result does
      not, however, suggest that ordering effect is a symptom of lexicographic
      ordering.

PMID- 16786551
TI  - Calcium-binding proteins, neuronal nitric oxide synthase, and GABA help to
      distinguish different pallial areas in the developing and adult chicken. I.
      Hippocampal formation and hyperpallium.
AB  - To better understand the formation and adult organization of the avian pallium,
      we studied the expression patterns of gamma-aminobutyric acid (GABA), calbindin
      (CB), calretinin (CR), and neuronal nitric oxide synthase (nNOS) in the
      hippocampal formation and hyperpallium of developing and adult chicks. Each
      marker showed a specific spatiotemporal expression pattern and was expressed in a
      region (area)-specific but dynamic manner during development. The combinatorial
      expression of these markers was very useful for identifying and following the
      development of subdivisions of the chicken hippocampal formation and
      hyperpallium. In the hyperpallium, three separate radially arranged subdivisions
      were present since early development showing distinct expression patterns: the
      apical hyperpallium (CB-rich); the intercalated hyperpallium (nNOS-rich, CB
      poor); the dorsal hyperpallium (nNOS-poor, CB-moderate). Furthermore, a novel
      division was identified (CB-rich, CR-rich), interposed between hyper- and
      mesopallium and related to the lamina separating both, termed laminar pallial
      nucleus. This gave rise at its surface to part of the lateral hyperpallium. Later
      in development, the interstitial nucleus of the apical hyperpallium became
      visible as a partition of the apical hyperpallium. In the hippocampal formation,
      at least five radial divisions were observed, and these were compared with the
      divisions proposed recently in adult pigeons. Of note, the corticoid dorsolateral
      area (sometimes referred as caudolateral part of the parahippocampal area)
      contained CB immunoreactivity patches coinciding with Nissl-stained cell
      aggregates, partially resembling the patches described in the mammalian
      entorhinal cortex. Each neurochemical marker was present in specific neuronal
      subpopulations and axonal networks, providing insights into the functional
      maturation of the chicken pallium.

PMID- 16786552
TI  - Histological and cytological study of the bed nuclei of the stria terminalis in
      adult rat. II. Oval nucleus: extrinsic inputs, cell types, neuropil, and neuronal
      modules.
AB  - The oval nucleus (Ov) of the bed nuclei of the stria terminalis was studied in
      adult rats. The Ov is composed of 11 neuron types distributed into a shell and a
      core domain. The stria terminalis, internal capsule, ventral amygdaloid pathway,
      and medial forebrain bundle are the main sources of afferents to the neuropil of
      the Ov. The nucleus shell contains abundant intrinsic neurons possibly connected
      among themselves and with the core by centripetal axon collaterals. Series of
      intrinsic neurons in the shell, linked with both short-axon and projecting
      neurons in the core, suggest a centripetal control of projecting neurons. In situ
      hybidization for vesicular glutamate transporter (VGlu) and glutamic acid
      decarboxylase (GAD) show numerous GAD-synthesizing neurons and an absence of VGlu
      synthesizing neurons. In the electron microscope, the neuropil of the Ov contains
      axospinous, axoshaft, axosomatic, mixed (i.e., chemical-electrical), and
      axoaxonic synapses, in order of frequency. Synaptic boutons in apposition with
      the initial segment, represent an additional axoaxonic interaction. Further
      neural synchronization of the Ov occurs via gap junctions between somata, soma
      dendrite, and possibly by apposition between axon terminals. The putative inputs
      from the major tracts of the forebrain coupled with the cytological organization
      of the Ov make it one of the most complex structures of the mammalian brain.

PMID- 16786553
TI  - SMN, the product of the spinal muscular atrophy-determining gene, is expressed
      widely but selectively in the developing human forebrain.
AB  - The expression pattern of the survival motor neuron (SMN) protein has been
      investigated immunohistochemically in the human fetal forebrain from 14 to 38
      weeks of gestation. Mutations in the SMN gene cause spinal muscular atrophy
      (SMA), an autosomal recessive disease characterized by degeneration of lower
      motor neurons in the spinal cord leading to progressive muscle wasting. SMN is a
      multifunctional protein and has been implicated in diverse cytoplasmic and
      nuclear processes. The monoclonal murine SMN antibody used in this study
      recognized a major band at approximately 34 kDa. In spinal cord anterior horn
      motor neurons at 13 weeks of gestation, the soma, proximal neurites, and nucleus
      were immunostained. In the nucleus, SMN immunolabeling was observed at the
      nuclear membrane, at the nucleolus, and at dot-like structures in the nucleoplasm
      likely to be coiled bodies and gems. In the fetal forebrain, SMN was
      immunodetected as early as 14 weeks of gestation. From 14 to 24 weeks of
      gestation, intense immunostaining was observed in the basal nucleus of Meynert, a
      major source of cholinergic afferents to the cortex. Less intensely labeled cells
      at lower packing density were also observed in the thalamus, reticular and
      perireticular nucleus, globus pallidus, hippocampus, amygdala, and enthorinal
      cortex. Immunolabeled cells were still detectable at 38 gestational weeks, the
      latest time point investigated. These findings provide an anatomical basis for
      future investigations of SMN functions during brain development and for the
      neuropathological characterization of severe SMA cases.

PMID- 16786554
TI  - Epithelial mitochondria-rich cells and associated innervation in adult and
      developing zebrafish.
AB  - Studies of ion regulation by mitochondria-rich cells (MRCs) of transport
      epithelia in fish have revealed many processes by which ion homeostasis is
      achieved. However, the control of these mechanisms and, particularly, the extent
      of nervous system involvement are not completely understood. We characterized the
      potential innervation of MRCs in various gill and extrabranchial tissues involved
      in ion transport in the model vertebrate the zebrafish. Confocal and conventional
      microscopy of whole-mount preparations were combined with immunofluorescence
      techniques to label MRCs with antibodies against a subunit of the enzyme
      Na(+)/K(+)-ATPase and nerve fibers with a zebrafish neuronal marker, zn-12. MRCs
      of the gill filaments were identified by their morphology and migration out to
      the lamellae in response to ion-poor water acclimation. Gill MRCs were intimately
      associated with nerve fibers originating from outside the filaments. MRCs of the
      opercular epithelium resembled those of the gill and were also located adjacent
      to nerve fibers. Mitochondria-rich "pseudobranch cells" were identified in the
      pseudobranch by immunofluorescence and labeling of dissociated cells with the
      mitochondrial marker DASPEI. Pseudobranch MRCs resembled gill MRCs and received
      innervation from a dense network of nerve fibers. In larvae, MRCs were
      distributed across the surface of the skin. These cells were situated among a
      dense network of varicose nerve fibers, and some MRCs of the skin displayed
      extensive cytoplasmic processes. Evidence is presented suggestive of widespread
      association of MRCs with the nervous system in transport epithelia and the neural
      control of MRC-mediated ion regulation in teleost fish.

PMID- 16786556
TI  - Exploring the cell's network with molecular imaging.
AB  - Molecular imaging is already a powerful tool for investigating molecular
      interactions within the cell. Interpreting molecular imaging findings will,
      however, take us into the more unfamiliar, nonlinear realm of networks. The
      network class of interest is the "scale-free" network, which characterizes not
      only the cell, but also surprisingly, other real work networks such as the world
      wide web. This network topology yields insights in how the cell is functionally
      organized via motifs, modules, and different types of hubs. Additional
      organizational information is gained from the cell's evolutionary history.
      Interpretation of molecular images will be deepened by a both qualitative and
      quantitative knowledge of the cell's network. Importantly, cell network behavior
      can be independent of molecular detail. For this reason, the same molecule can
      serve different functions in different cells or even within the same cell. Since
      a scale-free network's behavior is likely to be nonlinear and exhibit emergent
      behavior, a degree of caution is prudent in assigning cause and effect to
      molecular imaging findings in our effort to reengineer some of the cell's
      functions. Molecular imagers will need to be cognizant of the level of
      organization in the cell's network they are interrogating.

PMID- 16786555
TI  - Postnatal cellular contributions of the hippocampus subventricular zone to the
      dentate gyrus, corpus callosum, fimbria, and cerebral cortex.
AB  - The rodent dentate gyrus (DG) is formed in the embryo when progenitor cells
      migrate from the dentate neuroepithelium to establish a germinal zone in the
      hilus and a secondary germinal matrix, near the fimbria, called the hippocampal
      subventricular zone (HSVZ). The developmental plasticity of progenitors within
      the HSVZ is not well understood. To delineate the migratory routes and fates of
      progenitors within this zone, we injected a replication-incompetent retrovirus,
      encoding the enhanced green fluorescent protein (EGFP), into the HSVZ of
      postnatal day 5 (P5) mice. Between P6 and P45, retrovirally-infected EGFP(+) of
      progenitors migrated into the DG, established a reservoir of progenitor cells,
      and differentiated into neurons and glia. By P6-7, EGFP(+) cells were observed
      migrating into the DG. Subsets of these EGFP(+) cells expressed Sox2 and Musashi
      1, characteristic of neural stem cells. By P10, EGFP(+) cells assumed positions
      within the DG and expressed immature neuronal markers. By P20, many EGFP(+) cells
      expressed the homeobox prospero-like protein Prox1, an early and specific granule
      cell marker in the CNS, and extended mossy fiber projections into the CA3. A
      subset of non-neuronal EGFP(+) cells in the dentate gyrus acquired the morphology
      of astrocytes. Another subset included EGFP(+)/RIP(+) oligodendrocytes that
      migrated into the fimbria, corpus callosum, and cerebral cortex. Retroviral
      injections on P15 labeled very few cells, suggesting depletion of HSVZ
      progenitors by this age. These findings suggest that the early postnatal HSVZ
      progenitors are multipotent and migratory, and contribute to both dentate gyrus
      neurogenesis as well as forebrain gliogenesis.

PMID- 16786557
TI  - Spatial firing properties of lateral septal neurons.
AB  - The present study describes the spatial firing properties of neurons in the
      lateral septum (LS). LS neuronal activity was recorded in rats as they performed
      a spatial navigation task in an open field. In this task, the rat acquired an
      intracranial self-stimulation reward when it entered a certain place, a location
      that varied randomly from trial to trial. Of 193 neurons recorded in the LS, 81
      showed place-related activity. The majority of the tested neurons changed place
      related activity when spatial relations between environmental cues were altered
      by rotating intrafield (proximal) cues. The comparison of place activities
      between LS place-related neurons recorded in the present study and hippocampal
      place cells recorded in our previous study, using identical behavioral and
      recording procedures, revealed that spatial parameters (spatial information
      content, coherence, and cluster size) were smaller in the LS than in the
      hippocampus. Of the 193 LS neurons, 86 were influenced by intracranial self
      stimulation rewards; 31 of these 86 were also place-related. These results,
      together with previous anatomical and behavioral observations, suggest that the
      spatial information sent from the hippocampus to the LS is modulated by and
      interacts with signals related to reward in the LS.

PMID- 16786559
TI  - Innervation of dorsal and caudal fin muscles in adult zebrafish Danio rerio.
AB  - The organization of the neuromuscular system of the dorsal and caudal fin of
      zebrafish, Danio rerio, was studied, including the anatomy of fin motoneurons as
      revealed by neurobiotin backfills and differential staining using fluorescent
      markers. The musculature of the dorsal fin consists of one pair of protractor and
      retractor muscles and 10 sets of muscles attaching to the bases of dorsal fin
      rays. Each set consists of one pair of erector, depressor, and inclinator
      muscles. The supplying nerves of the dorsal fin musculature originate from spinal
      segments 9-17 and form a dorsal fin plexus at the base of the muscles. Dorsal and
      caudal fin motoneurons have small cell bodies and ipsilateral dendritic branching
      patterns, thus resembling secondary motoneurons of the axial musculature. As
      shown by differential staining using fluorescent-labeled dextrans, cell bodies of
      dorsal fin motoneurons and axial motoneurons seem to be located in separate motor
      columns. The musculature of the caudal fin is composed of 12 muscles that are
      arranged in a superficial and a deep muscle layer. The nerves that supply the
      caudal fin musculature arise from the last five caudal segments of the spinal
      cord and form the caudal plexus. Neurobiotin backfills were performed on the
      dorsal caudal muscles, the medial caudal muscles, and the ventral caudal muscles.
      Most cell bodies of caudal fin motoneurons are small and are located in a ventral
      motor column. The organization of dorsal and caudal fin motoneurons is compared
      with the innervation of fins in other fish.

PMID- 16786558
TI  - Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord,
      with a note on the spinocervical tract.
AB  - To evaluate whether the organization of glutamatergic fibers systems in the
      lumbar cord is also evident at other spinal levels, we examined the
      immunocytochemical distribution of vesicle glutamate transporters 1 and 2
      (VGLUT1, VGLUT2) at several different levels of the rat spinal cord. We also
      examined the expression of VGLUTs in an ascending sensory pathway, the
      spinocervical tract, and colocalization of VGLUT1 and VGLUT2. Mainly small VGLUT2
      immunoreactive varicosities occurred at relatively high densities in most areas,
      with the highest density in laminae I-II. VGLUT1 immunolabeling, including small
      and medium-sized to large varicosities, was more differentiated, with the highest
      density in the deep dorsal horn and in certain nuclei such as the internal
      basilar nucleus, the central cervical nucleus, and the column of Clarke. Lamina I
      and IIo displayed a moderate density of small VGLUT1 varicosities at all spinal
      levels, although in the spinal enlargements a uniform density of such
      varicosities was evident throughout laminae I-II in the medial half of the dorsal
      horn. Corticospinal tract axons displayed VGLUT1, indicating that the
      corticospinal tract is an important source of small VGLUT1 varicosities. VGLUT1
      and VGLUT2 were cocontained in small numbers of varicosities in laminae III-IV
      and IX. Anterogradely labeled spinocervical tract terminals in the lateral
      cervical nucleus were VGLUT2 immunoreactive. In conclusion, the principal
      distribution patterns of VGLUT1 and VGLUT2 are essentially similar throughout the
      rostrocaudal extension of the spinal cord. The mediolateral differences in VGLUT1
      distribution in laminae I-II suggest dual origins of VGLUT1-immunoreactive
      varicosities in this region.

PMID- 16786560
TI  - Ontogeny of the somatostatin variant [Pro2,Met13]somatostatin-14 in the brain,
      pituitary, and sensory organs of the frog Rana esculenta.
AB  - Two forms of somatostatin are expressed in the frog brain, i.e., somatostatin-14
      (SS1) and the [Pro(2), Met(13)]somatostatin-14 variant (SS2). We have previously
      described the ontogeny of SS1-immunoreactive cells in the brain of Rana
      esculenta. In the present study, we have investigated the distribution of prepro
      SS2 (PSS2)-expressing neurons in the brain of the same species during development
      by using antibodies directed against the N-flanking region of SS2 (PSS2(54-66)).
      Immunoreactive perikarya first appeared in the ventral hypothalamus at stages IV
      VII. Subsequently, positive neurons were seen in the nucleus of the diagonal band
      of Broca, the anterior preoptic area, the posterior tuberculum (stages VIII-XII),
      as well as the dorsal (stages XIII-XV) and medial (stages XIX-XX) periventricular
      preoptic nucleus. At metamorphic climax and in newly metamorphosed frogs,
      positive perikarya were found in the striatum and in the interpeduncular nucleus.
      PSS2(54-66)-immunoreactive fibers were already widely distributed during the
      first stages of development, indicating that SS2 may act as a neuromodulator
      and/or neurotransmitter during ontogeny. The presence of PSS2(54-66)-positive
      nerve fibers in olfactory structures suggests that, in tadpoles, SS2 may be
      involved in the processing of olfactory information. The occurrence of PSS2(54
      66)-like immunoreactivity in taste buds, and in the olfactory and vomeronasal
      organs indicates that SS2 may mediate the unconditioned and reinforcing
      properties of natural chemicals. Finally, the intenseexpression of PSS2(54-66)
      like immunoreactivity in melanotrope cells of the pituitary suggests that SS2 may
      diffuse toward the pars distalis to regulate the activity of adenohypophysial
      cells during tadpole development.

PMID- 16786561
TI  - Psychosis pathways converge via D2high dopamine receptors.
AB  - The objective of this review is to identify a target or biomarker of altered
      neurochemical sensitivity that is common to the many animal models of human
      psychoses associated with street drugs, brain injury, steroid use, birth injury,
      and gene alterations. Psychosis in humans can be caused by amphetamine,
      phencyclidine, steroids, ethanol, and brain lesions such as hippocampal,
      cortical, and entorhinal lesions. Strikingly, all of these drugs and lesions in
      rats lead to dopamine supersensitivity and increase the high-affinity states of
      dopamine D2 receptors, or D2High, by 200-400% in striata. Similar
      supersensitivity and D2High elevations occur in rats born by Caesarian section
      and in rats treated with corticosterone or antipsychotics such as reserpine,
      risperidone, haloperidol, olanzapine, quetiapine, and clozapine, with the latter
      two inducing elevated D2High states less than that caused by haloperidol or
      olanzapine. Mice born with gene knockouts of some possible schizophrenia
      susceptibility genes are dopamine supersensitive, and their striata reveal
      markedly elevated D2High states; suchgenes include dopamine-beta-hydroxylase,
      dopamine D4 receptors, G protein receptor kinase 6, tyrosine hydroxylase,
      catechol-O-methyltransferase, the trace amine-1 receptor, regulator of G protein
      signaling RGS9, and the RIIbeta form of cAMP-dependent protein kinase (PKA).
      Striata from mice that are not dopamine supersensitive did not reveal elevated
      D2High states; these include mice with knockouts of adenosine A2A receptors,
      glycogen synthase kinase GSK3beta, metabotropic glutamate receptor 5, dopamine D1
      or D3 receptors, histamine H1, H2, or H3 receptors, and rats treated with
      ketanserin or aD1 antagonist. The evidence suggests that there are multiple
      pathways that convergetoelevate the D2High state in brain regions and that this
      elevation may elicit psychosis. This proposition is supported by the dopamine
      supersensitivity that is a common feature of schizophrenia and that also occurs
      in many types of genetically altered, drug-altered, and lesion-altered animals.
      Dopamine supersensitivity, in turn, correlates with D2High states. The finding
      that all antipsychotics, traditional and recent ones, act on D2High dopamine
      receptors further supports the proposition.

PMID- 16786563
TI  - Intravenous contrast-enhanced dynamic MR urography: diagnosis of vesicoureteral
      reflux during bladder filling with time-signal intensity curves.
AB  - PURPOSE: To evaluate the time-signal intensity (SI) curves generated from
      intravenous (IV) gadodiamide-enhanced dynamic magnetic resonance (MR) urographic
      scans for identifying vesicoureteral reflux (VUR) during bladder filling.
      MATERIALS AND METHODS: MR urographic studies of children were retrospectively
      reviewed, and 52 ureterorenal units of 26 patients (15 females and 11 males, mean
      age = 5.5 years) who had also undergone voiding cystourethrographic (VCUG)
      examination were included in this study. The patients were examined on a 1.5T
      scanner. For functional MR urography and to generate time-SI curves, we used a
      post IV contrast-enhanced two-dimensional (2D) fast field echo (FFE) sequence (TR
      = 17 msec, TE = 3.2 msec, flip angle (FA) = 90 degrees ) in the coronal plane. MR
      urographic time-SI curves that demonstrated a prompt and concave fall of the
      initial third phase followed by intermittent or constantly increasing SI peaks
      above the baseline from which the second phase starts were considered to have
      VUR. We compared the differences in time-SI curves between the control group and
      patients with VUR during bladder filling. RESULTS: Twelve ureterorenal units of
      eight patients (four bilateral and four unilateral) had VUR during bladder
      filling on VCUG. The time-SI curves of these patients showed intermittent (N = 8
      ureterorenal units), and constantly increasing (N = 4 ureterorenal units) SI
      peaks consistent with VUR. One patient also had bilateral abnormal time-SI curves
      suggesting VUR despite the normal VCUG study. In the control group, 25 units had
      normal triphase time-SI curves, six renal units had urinary dilatation with good
      washout after diuretic injection, and four renal units had upper urinary
      dilatation without contrast washout, while five renal units did not show any
      function. None of the patients in the control group revealed distortion in the
      time-SI curve. The differences in time-SI curves patterns between the control
      group and patients with VUR during bladder filling were statistically significant
      (P < 0.001). CONCLUSION: After a prompt and concave decrease of the initial third
      phase of the time-SI curve, intermittent spikes or a constant rise in SI above
      the baseline suggest the existence of VUR.

PMID- 16786564
TI  - Comparison of myocardial velocities obtained with magnetic resonance phase
      velocity mapping and tissue Doppler imaging in normal subjects and patients with
      left ventricular dyssynchrony.
AB  - PURPOSE: To compare longitudinal myocardial velocity and time to peak
      longitudinal velocity obtained with magnetic resonance phase velocity mapping (MR
      PVM) and tissue Doppler imaging (TDI), and to assess the reproducibility of each
      method. MATERIALS AND METHODS: Longitudinal myocardial velocity was measured by
      TDI and MR-PVM in 10 normal volunteers and 10 patients with dyssynchrony. The
      reproducibility of MR-PVM and TDI was assessed on repeated measurements in the 10
      normal volunteers. RESULTS: MR and TDI measurements of longitudinal myocardial
      velocity correlated well (r = 0.86) in both normal subjects and patients with
      dyssynchrony. However, myocardial velocities measured with MR consistently
      exceeded velocities measured with TDI. MR and TDI agreed strongly in measuring
      the time to peak velocity (r = 0.97). The reproducibility of TDI and MR-PVM
      appeared similar in measuring peak velocities (13.1% vs. 11.0%, respectively; P =
      NS) and time to peak velocity (9.1% vs. 5.7%, respectively; P = NS). CONCLUSION:
      Excellent correlation and reproducibility were observed between MR-PVM and TDI in
      measuring longitudinal myocardial velocity and time to peak velocity in both
      normal subjects and patients with dyssynchrony.

PMID- 16786562
TI  - Distribution of EphB receptors and ephrin-B1 in the developing vertebrate spinal
      cord.
AB  - Contact-dependent interactions between EphB receptors and ephrin-B ligands
      mediate a variety of cell-cell communication events in the developing and mature
      central nervous system (CNS). These predominantly repulsive interactions occur at
      the interface between what are considered to be mutually exclusive EphB and
      ephrin-B expression domains. We previously used receptor and ligand affinity
      probes to show that ephrin-B ligands are expressed in the floor plate and within
      a dorsal region of the embryonic mouse spinal cord, while EphB receptors are
      present on decussated segments of commissural axons that navigate between these
      ephrin-B domains. Here we present the generation and characterization of two new
      monoclonal antibodies, mAb EfB1-3, which recognizes EphB1, EphB2, and EphB3, and
      mAb efrnB1, which is specific for ephrin-B1. We use these reagents and polyclonal
      antibodies specific for EphB1, EphB2, EphB3, or ephrin-B1 to describe the
      spatiotemporal expression patterns of EphB receptors and ephrin-B1 in the
      vertebrate spinal cord. Consistent with affinity probe binding, we show that
      EphB1, EphB2, and EphB3 are each preferentially expressed on decussated segments
      of commissural axons in vivo and in vitro, and that ephrin-B1 is expressed in a
      dorsal domain of the spinal cord that includes the roof plate. In contrast to
      affinity probe binding profiles, we show here that EphB1, EphB2, and EphB3 are
      present on the ventral commissure, and that EphB1 and EphB3 are expressed on
      axons that compose the dorsal funiculus. In addition, we unexpectedly find that
      mesenchymal cells, which surround the spinal cord and dorsal root ganglion,
      express ephrin-B1.

PMID- 16786565
TI  - Quantitative diffusion imaging in breast cancer: a clinical prospective study.
AB  - PURPOSE: To study the correlation between apparent diffusion coefficient (ADC)
      and pathology in patients with undefined breast lesion, to validate how
      accurately ADC is related to histology, and to define a threshold value of ADC to
      distinguish malignant from benign lesions. MATERIALS AND METHODS: Seventy-eight
      patients (110 lesions) were referred for positive or dubious findings. Three
      dimensional fast low-angle shot (3D-FLASH) with contrast injection was applied.
      EPI diffusion-weighted imaging (DWI) with fat saturation was performed, and ROIs
      were selected on subtraction 3D-FLASH images before and after contrast injection,
      and copied on an ADC map. Inter- and intraobserver analyses were performed.
      RESULTS: At pathology 22 lesions were benign, 65 were malignant, and 23 were
      excluded. The ADCs of malignant and benign lesions were statistically different.
      In malignant tumors the ADC was (mean +/- SEM) 0.95 +/- 0.027 x 10(
      3)mm(2)/second, and in benign tumors it was 1.51 +/- 0.068 x 10(-3)mm(2)/second.
      According to receiver operating characteristic (ROC) curves, we found a threshold
      between malignant and benign lesions for highest sensitivity and specificity
      (both 86%) around 1.13 +/- 0.10 x 10(-3)mm(2)/second. For a threshold of 0.95 +/-
      0.10 x 10(-3)mm(2)/second, specificity was 100% but sensitivity was very low.
      Inter- and intraobserver studies showed good reproducibility. CONCLUSION: The ADC
      may help to differentiate benign and malignant lesions with good specificity, and
      may increase the overall specificity of breast MRI.

PMID- 16786567
TI  - Monitoring the therapeutic response of locally advanced breast cancer patients:
      sequential in vivo proton MR spectroscopy study.
AB  - PURPOSE: To evaluate the use of the water-to-fat (W-F) value obtained from in
      vivo proton ((1)H) MR spectroscopy (MRS) as a response indicator of cytologically
      confirmed patients with locally advanced breast cancer (LABC), and to monitor the
      therapeutic response of such patients to neoadjuvant chemotherapy (NACT).
      MATERIALS AND METHODS: Serial (1)H MR spectra were recorded both before and after
      the completion of chemotherapy in 33 LABC patients (with infiltrating ductal
      carcinoma (IDC)) at 1.5T. In addition, spectra from normal breast tissues of 28
      healthy volunteers were recorded. RESULTS: Malignant breast tissues showed
      elevated W-F values compared to normal breast tissues of controls. Statistically
      significant higher pretherapy W-F value (P < 0.01) was observed in patients
      compared to controls. In patients who received NACT resulting in the reduction of
      the primary tumor size, the W-F value showed a decrease that was statistically
      significant (P < 0.01). Analysis of the MR data further indicates that the W-F
      value had no correlation with the menstrual status of the patients. A comparison
      of pretherapy W-F value with pretherapy tumor volume showed a fair correlation (P
      = 0.05), while the posttherapy W-F value showed no such correlation with the
      posttherapy tumor volume. CONCLUSION: This study demonstrates that simple,
      conventional in vivo (1)H MRS is a useful technique for monitoring the
      therapeutic response of breast cancer patients. The observed trend in the
      reduction of W-F value provides a noninvasive response indicator to monitor the
      clinical outcome of locally advanced breast cancer patients to NACT.

PMID- 16786566
TI  - Dynamic pulmonary perfusion and flow quantification with MR imaging, 3.0T vs.
      1.5T: initial results.
AB  - PURPOSE: To prospectively evaluate the technical feasibility and relative
      performance of pulmonary time-resolved MR angiography (MRA) and pulmonary artery
      (PA) flow quantification at 3.0T vs. 1.5T. MATERIALS AND METHODS: Time-resolved
      contrast-enhanced (CE) MRA of the pulmonary circulation, and flow quantification
      of the main PA (MPA) were performed in 14 consecutive adult healthy volunteers at
      both 1.5 and 3.0 Tesla with nearly identical sequence parameters. Image quality,
      signal-to-noise ratio (SNR), and quantitative indices of pulmonary perfusion,
      flow, and velocity were evaluated and compared at both field strengths. RESULTS:
      Time-resolved pulmonary MRA, perfusion, and flow quantification were successfully
      performed at both magnetic fields. The results of pulmonary perfusion and flow
      indices were comparable at both magnetic fields, with no statistically
      significant difference. The SNR values for vascular structures were higher at
      3.0T vs. 1.5T (P = 0.001). The SNR values and the definition scores for
      parenchymal enhancement were significantly lower (P = 0.008 and 0.001,
      respectively) at 3.0T. CONCLUSION: Time-resolved pulmonary MRA, perfusion, and
      flow quantification at 3.0T was feasible, with comparable results to 1.5T. The
      lower parenchymal enhancement at 3.0T is believed to reflect increased
      susceptibility effects at higher magnetic fields. Further work is needed to fully
      exploit the potential of pulmonary perfusion imaging at 3.0T and to address the
      current limitations.

PMID- 16786568
TI  - Delivery and assessment of endovascular stents to repair aortic coarctation using
      MR and X-ray imaging.
AB  - PURPOSE: To investigate the utility of MR and X-ray imaging for characterizing
      aortic coarctation and flow, and guiding the endovascular catheter to place a
      stent to repair the coarctation. MATERIALS AND METHODS: The descending aorta in
      eight dogs was looped with elastic band and tightened distal to the subclavian
      artery. Balanced fast field echo (bFFE) and velocity-encoded cine (VEC) MRI
      sequences were used for device tracking and measuring aortic flow. A T1-weighted
      fast-field echo sequence (T1-FFE) was used to visualize the coarctation and
      roadmap the aorta. Nitinol stents were guided by a nitinol guidewire and placed
      under MR guidance. RESULTS: Aortic coarctation was visible on MR and X-ray
      imaging. The procedure success rate was 88%. VEC MRI measured the changes in
      aortic flow (baseline = 1.3 +/- 0.2, coarctation = 0.2 +/- 0.02, and stent
      placement = 0.8 +/- 0.1 liters/minute). A significant reduction in iliac blood
      pressure was measured after coarctation, but it was reversed by stent placement.
      The stent lumen was visible on X-ray fluoroscopy, but not on MRI. CONCLUSION:
      Stent deployment to repair aortic coarctation is feasible under MR guidance. The
      combined use of MR and X-ray imaging is effective for anatomic and functional
      evaluation of aortic coarctation dilation, which may be crucial for optimal
      therapy.

PMID- 16786569
TI  - Bone metastases from head and neck paragangliomas: uncommon MR findings in an
      uncommon condition--report of three cases.
AB  - Malignancy (defined as metastatic disease) has been reported in nearly 5% of head
      and neck paragangliomas. Metastases preferentially target the lymph nodes, lung,
      liver, or bone. We describe three patients with multiple silent bone metastases
      exhibiting a fatty halo at MRI that coexisted with expansive bone lesions. In all
      cases, (123)I-metaiodobenzylguanidine ((123)MIBG) scintigraphy showed no abnormal
      tracer uptake, whereas (111)In-pentetreotide scintigraphy visualized a few silent
      bone metastases. These findings indicate that MRI should be included in the
      staging of paraganglioma patients with risk factors for malignancy.

PMID- 16786571
TI  - Accelerated volumetric MRI with a SENSE/GRAPPA combination.
AB  - PURPOSE: To combine the specific advantages of the generalized autocalibrating
      partially parallel acquisitions (GRAPPA) technique and sensitivity encoding
      (SENSE) with two-dimensional (2D) undersampling. MATERIALS AND METHODS: By
      splitting the 2D reconstruction process into multiple one-dimensional (1D)
      reconstructions, the normal 1D GRAPPA method can be used for image
      reconstruction. Due to this data-handling process, a GRAPPA reconstruction is
      performed along the phase-encoding (PE) direction and effectively a SENSE
      reconstruction is performed along the partition-encoding (PAE) direction.
      RESULTS: In vivo experiments demonstrate the successful implementation of the
      SENSE/GRAPPA combination. Experimental results with up to 9.6-fold acceleration
      using a prototype 32-channel receiver head coil array are presented. CONCLUSION:
      The proposed SENSE/GRAPPA combination for 3D imaging allows the GRAPPA method to
      be applied in combination with 2D undersampling. Because the SENSE/GRAPPA
      combination is not based on knowledge of spatial coil sensitivities, it should be
      the method of choice whenever it is difficult to extract the sensitivity
      information.

PMID- 16786570
TI  - p53-Mediated enhancement of radiosensitivity by selenophosphate synthetase 1
      overexpression.
AB  - Selenium has been associated with cancer prevention. Despite vast knowledge of
      selenium effect on various health conditions, functional characterization of
      selenium metabolic enzymes on cellular physiology has been limited. Therefore, to
      gain insight into the mechanisms underlying cancer prevention by selenium, we
      investigated sps1, one of the two human selenophosphate synthetase genes for its
      role in cancer cell's response to ionizing radiation. Although stable expression
      of Sps1 protein per se had little effect on cell proliferation, concurrent
      irradiation decreased viability of the sps1 cell line. The increased sensitivity
      of the cell lines to ionizing radiation was correlated with increased p53
      activity as well as with simultaneous up- and downregulation of Bax and Bcl2,
      respectively. Knockdown of sps1 and p53 by small interfering RNA method revealed
      that the level of p53 was proportional to that of Sps1 and that the increased
      radiosensitivity was dependent upon p53. Sps1 cell lines displayed decreased
      level of reactive oxygen species (ROS) with concomitant increase of certain redox
      enzymes. Furthermore, p53 activity was regulated by cellular redox via Ref1 in
      sps1 cell lines. Collectively, our results demonstrated that sps1 was able to
      affect cell viability upon ionizing radiation via modulation of p53 activity.
      They further suggest that Sps1 and its reaction product selenophosphate might be
      involved in cancer prevention in a p53-dependent manner and could be applied to
      development of a novel cancer therapy.

PMID- 16786572
TI  - High-resolution, time-resolved MRA provides superior definition of lower
      extremity arterial segments compared to 2D time-of-flight imaging.
AB  - PURPOSE: To evaluate a novel time-resolved contrast-enhanced (CE) projection
      reconstruction (PR) magnetic resonance angiography (MRA) method for identifying
      potential bypass graft target vessels in patients with Class II-IV peripheral
      vascular disease. MATERIALS AND METHODS: Twenty patients (M:F = 15:5, mean age =
      58 years, range = 48-83 years), were recruited from routine MRA referrals. All
      imaging was performed on a 1.5 T MRI system with fast gradients (Signa LX; GE
      Healthcare, Waukesha, WI). Images were acquired with a novel technique that
      combined undersampled PR with a time-resolved acquisition to yield an MRA method
      with high temporal and spatial resolution. The method is called PR hyper time
      resolved imaging of contrast kinetics (PR-hyperTRICKS). Quantitative and
      qualitative analyses were used to compare two-dimensional (2D) time-of-flight
      (TOF) and PR-hyperTRICKS in 13 arterial segments per lower extremity. Statistical
      analysis was performed with the Wilcoxon signed-rank test. RESULTS: Fifteen
      percent (77/517) of the vessels were scored as missing or nondiagnostic with 2D
      TOF, but were scored as diagnostic with PR-hyperTRICKS. Image quality was
      superior with PR-hyperTRICKS vs. 2D TOF (on a four-point scale, mean rank = 3.3
      +/- 1.2 vs. 2.9 +/- 1.2, P < 0.0001). PR-hyperTRICKS produced images with high
      contrast-to-noise ratios (CNR) and high spatial and temporal resolution. 2D TOF
      images were of inferior quality due to moderate spatial resolution, inferior CNR,
      greater flow-related artifacts, and absence of temporal resolution. CONCLUSION:
      PR-hyperTRICKS provides superior preoperative assessment of lower limb ischemia
      compared to 2D TOF.

PMID- 16786573
TI  - Dynamic MR perfusion and proton MR spectroscopic imaging in Sturge-Weber
      syndrome: correlation with neurological symptoms.
AB  - PURPOSE: To investigate physiological alterations in Sturge-Weber syndrome (SWS)
      using MR perfusion imaging (PWI) and proton spectroscopic imaging (MRSI), and
      their association with neurological status. MATERIALS AND METHODS: Six
      consecutive patients with a clinically established diagnosis of SWS underwent MRI
      using a 1.5 Tesla scanner. The protocol consisted of conventional anatomic scans,
      dynamic PWI, and multislice MRSI. A pediatric neurologist evaluated the
      neurological scores, and the imaging results were correlated with neurological
      scores using nonparametric correlation analysis. RESULTS: Two patients had
      classic neuroimaging findings of unilateral cerebral atrophy with corresponding
      leptomeningeal enhancement and hypoperfusion (prolonged mean transit time). Two
      patients had bilateral disease, and two had normal symmetric perfusion. Among
      clinical measures, the highest correlation was between hemiparesis index and
      hypoperfused tissue volume (Spearman's correlation coefficient, rho = 0.943, P <
      0.05). There was also a trend of correlation, although not statistically
      significant (P = 0.06), between the hemiparesis score and the NAA/Cr ratio in the
      mid to posterior centrum semiovale, lateral gray matter (GM), and splenium.
      CONCLUSION: In SWS, PWI indicates cerebral hypoperfusion predominantly due to
      impaired venous drainage, with only the most severely affected regions in some
      patients also showing arterial perfusion deficiency. The extent and severity of
      the perfusion abnormality and neuronal loss/dysfunction reflect the severity of
      neurological symptoms and disability, and the highest correlation is found with
      the degree of hemiparesis. These parameters may be useful as quantitative
      measures of disease burden; however, further studies in larger number of patients
      (and with a more homogeneous age range) are required to confirm the preliminary
      findings reported here.

PMID- 16786575
TI  - Comparison of Schwann cell and sciatic nerve transcriptomes indicates that mouse
      is a valid model for the human peripheral nervous system.
AB  - High-throughput gene expression analyses of murine models of the peripheral
      nervous system (PNS), and its cellular components, have yielded enormous amounts
      of expression data of the PNS in various conditions. These data provided clues
      for future research directions to further decipher this complex organ in relation
      to acquired and inherited PNS diseases. Various studies addressing the validity
      of mouse models for human conditions in other tissues and cell types have
      indicated that in many cases the mouse model only poorly represents the human
      situation. To determine how well the mouse can serve as model to study the
      biological processes occurring in the PNS, we compared the gene expression
      profiles that we generated for mouse and human sciatic nerve and cultured Schwann
      cells derived thereof. A two-way analysis based on the differentially expressed
      genes between the sciatic nerve and the cultured Schwann cell, and which takes
      into account the differential expression between mouse and man, indicates that
      the human PNS is well represented by that of the mouse in terms of the
      "biological processes" ontology.

PMID- 16786574
TI  - Gene delivery to the spinal cord: comparison between lentiviral, adenoviral, and
      retroviral vector delivery systems.
AB  - Viral gene delivery for spinal cord injury (SCI) is a promising approach for
      enhancing axonal regeneration and neuroprotection. An understanding of spatio
      temporal transgene expression in the spinal cord is essential for future studies
      of SCI therapies. Commonly, intracellular marker proteins (e.g., EGFP) were used
      as indicators of transgene levels after viral delivery, which may not accurately
      reflect levels of secreted transgene. This study examined transgene expression
      using ELISA after viral delivery of D15A, a neurotrophin with BDNF and NT-3
      activities, at 1, 2, and 4weeks after in vivo and ex vivo delivery using
      lentiviral, adenoviral, and retroviral vectors. Further, the inflammatory
      responses and viral infection patterns after in vivo delivery were examined.
      Lentiviral vectors had the most stable pattern of gene expression, with D15A
      levels of 536 +/- 38 and 363 +/- 47 pg/mg protein seen at 4 weeks after the in
      vivo and ex vivo delivery, respectively. Our results show that protein levels
      downregulate disproportionately to levels of EGFP after adenoviral vectors both
      in vivo and ex vivo. D15A dropped from initial levels of 422 +/- 87 to 153 +/- 18
      pg/mg protein at 4 weeks after in vivo administration. Similarly, ex vivo
      retrovirus-mediated transgene expression exhibited rapid downregulation by 2
      weeks post-grafting. Compared to adenoviral infection, macrophage activation was
      attenuated after lentiviral infection. These results suggest that lentiviral
      vectors are most suitable in situations where stable long-term transgene
      expression is needed. Retroviral ex vivo delivery is optional when transient
      expression within targeted spinal tissue is desired, with adenoviral vectors in
      between.

PMID- 16786577
TI  - Whole-body T1 mapping improves the definition of adipose tissue: consequences for
      automated image analysis.
AB  - PURPOSE: To determine whether a whole-body T1-mapping acquisition method improves
      the definition of adipose tissue (AT) and simplifies automated AT segmentation
      compared to an image-based method. MATERIALS AND METHODS: The study included 10
      subjects. Two whole-body volumes were acquired from each subject using two
      different flip angles. Whole-body T1 maps were calculated from each pair of whole
      body volumes. AT was automatically segmented from the T1 maps and from the
      original image slices. The results were evaluated using manually segmented slices
      as reference. RESULTS: The T1-mapping method segmented more of the reference AT
      than the image-based method, with mean values (standard deviations (SDs)) of
      87.7(5.1)% and 81.1(5.2)%, respectively. Compared to the image-based method, the
      T1-mapping method gives better histogram separation of AT in whole-body volumes.
      The suggested method also provides an output with smaller in-slice AT intensity
      variations. CONCLUSION: The T1-mapping method improves the definition of AT. T1
      based analysis is superior to analysis based on the original images, and allows
      fully automated and accurate whole-body AT segmentation.

PMID- 16786576
TI  - Study on the toxic mechanism of prion protein peptide 106-126 in neuronal and non
      neuronal cells.
AB  - A synthetic peptide corresponding to the 106-126 amyloidogenic region of the
      cellular human prion protein (PrP(c)) is useful for in vitro study of prion
      induced neuronal cell death. The aim of the present work was to examine the
      implication of the cellular prion protein in the toxicity mechanism induced by
      PrP 106-126. The effect of PrP 106-126 was investigated both on human
      neuroblastoma SH-SY5Y cells and on SH-SY5Y overexpressing murine cellular prions
      (wtPrP). We show by metabolic assay tests and ATP assays that PrP(c) expression
      does not modulate the toxicity of the prion peptide. Moreover, we investigated
      the effect of this peptide on an established non neuronal model, rabbit kidney
      epithelial A74 cells that express a doxycycline-inducible murine PrP(c) gene. We
      show for the first time that the prion peptide 106-126 does not exert any toxic
      effect on this cell line in the presence or absence of doxycycline. Our results
      show that the PrP 106-126-induced cell alteration is independent of PrP(c)
      expression. Rather, it seems to act via an interaction with lipidic components of
      the plasma membrane as strengthened by our results showing the differential
      susceptibility of neuronal and non neuronal cell lines that significantly differ
      by their membrane fatty acid composition.

PMID- 16786578
TI  - Temporal dynamics of neurite outgrowth promoted by basic fibroblast growth factor
      in chick ciliary ganglia.
AB  - Basic fibroblast growth factor (bFGF) is a potent and multifunctional
      neurotrophic factor that can influence neuronal survival and differentiation. It
      has been shown to modulate growth and orientation of neuritic processes both in
      intact organs and in neuronal cultures, with a wide spectrum of effects on
      different preparations. Here we report that it promotes neurite growth in
      developing parasympathetic neurons from the chick ciliary ganglion. We have used
      both organotypic cultures and dissociated neurons, and we have combined
      assessment of global neurite growth by immunocytochemical techniques with
      evaluation of dynamic parameters of single neurites via time-lapse microscopy. We
      show that laminin, a molecule of the extracellular matrix that has been
      associated with stimulation of neurite extension, has only a limited and short
      lived effect on neurite outgrowth. In contrast, bFGF can promote global growth of
      the neuritic network both in whole ganglia and in dissociated cultures for times
      up to 48 hr, and this effect is related to an increase in the growth rate of
      single neurites. Moreover, the effect can be observed even in enriched neuronal
      cultures, pointing to a direct action of bFGF on neurons.

PMID- 16786579
TI  - Monoclonal antibody Rip specifically recognizes 2',3'-cyclic nucleotide 3'
      phosphodiesterase in oligodendrocytes.
AB  - The antigen recognized with monoclonal antibody (mAb) Rip (Rip-antigen) has been
      long used as a marker of oligodendrocytes and myelin sheaths. However, the
      identity of Rip-antigen has yet to be elucidated. We herein identified the Rip
      antigen. No signal recognized by mAb-Rip was detected by immunoblot analyses in
      the rat brain, cultured rat oligodendrocytes, or the oligodendrocyte cell line CG
      4. As this antibody worked very well on immunocytochemistry and
      immunohistochemistry, Rip-antigen was immunopurified with mAb-Rip from the
      differentiated CG-4 cells. Eight strong-intensity bands thus appeared on 5-20%
      SDS-PAGE with SYPRO ruby fluorescence staining. To identify these molecules, each
      band extracted from the gel was analyzed by MALDI-QIT/TOF mass spectrometry. We
      found an interesting molecule in the oligodendrocytes from an approximately 44
      kDa band as 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). To test whether
      CNP was recognized by mAb-Rip, double-immunofluorescence staining was performed
      by using Alexa Fluor 488-conjugated mAb-Rip and Alexa Fluor 568-conjugated mAb
      CNP in the rat cerebellum, mouse cerebellum, cultured rat oligodendrocytes, and
      CG-4 cells. The Rip-antigen was colocalized with CNP in these cells and tissues.
      To provide direct evidence that CNP was recognized by mAb-Rip, rat Cnp1
      transfected HEK293T cells were used for double-immunofluorescence staining with
      mAb-Rip and mAb-CNP. The Rip-antigen was colocalized with CNP in rat Cnp1
      transfected HEK293T cells, but the antigen was not detected by mAb-Rip and mAb
      CNP in mock-transfected HEK293T cells. Overall, we have demonstrated that the
      antigen labeled with mAb-Rip is CNP in the oligodendrocytes.

PMID- 16786580
TI  - MRI, volumetry, 1H spectroscopy, and cerebropetal blood flowmetry in childhood
      idiopathic anatomic megalencephaly.
AB  - PURPOSE: To evaluate cerebral abnormalities in childhood idiopathic anatomic
      megalencephaly (MC) by means of different magnetic resonance (MR) modalities.
      MATERIALS AND METHODS: MRI, volumetry, spectroscopy, and cerebropetal blood
      flowmetry were performed in six children with idiopathic anatomic MC, and seven
      volunteers. RESULTS: MRI revealed an increased ventricular system in five of six
      patients. A thalamic hamartoma was found in one patient and a Chiari I
      malformation was found in two. Volumetric analysis showed a disproportional
      increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF)
      volume. Supratentorial volume was disproportionally increased compared to
      cerebellar volume. Intracranial volume correlated significantly with skull
      circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak
      ratios in WM were significantly higher in patients than in controls.
      Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients.
      Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was
      increased in MC, possibly related to increased brain volume. CONCLUSION: This
      study reveals associated developmental anomalies for idiopathic anatomic MC. A
      relative ventriculomegaly was found, which should not be misinterpreted as true
      hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances.
      Total intracranial volume is correlated to skull circumference and cerebropetal
      blood flow.

PMID- 16786582
TI  - B1 field, SAR, and SNR comparisons for birdcage, TEM, and microstrip coils at 7T.
AB  - PURPOSE: To compare the performance of birdcage, transverse electromagnetic (TEM)
      and microstrip volume coils at 7T under the same geometric conditions. MATERIALS
      AND METHODS: Birdcage, TEM, and microstrip coils are modeled with the same
      dimensions. The finite difference time domain (FDTD) method is adopted to
      calculate the electromagnetic fields of the coils. Further, B(1) field, specific
      absorption rate (SAR) and signal-to-noise ratio (SNR) are calculated for these
      coils. RESULTS: In the unloaded case, within the central axial plane, the
      variation of B(1) field magnitude over 18-cm distance is about 15% for the
      birdcage coil, 23% for the TEM coil, and 38% for the microstrip coil. In the
      loaded case, the percentages of the samples on the central axial plane, which
      have B(1) field magnitude within +/-20% of the average B(1) field magnitude, are
      about 57% for the birdcage, 72% for the TEM, and 59% for the microstrip coil.
      Average SAR levels are 11.4% and 42.9% higher in the birdcage than those in the
      TEM and microstrip coils, respectively. The average relative SNR on the central
      axial plane for the shielded birdcage, TEM, and microstrip coils are 1, 1.07, and
      1.48, respectively. CONCLUSION: The birdcage coil has the best unloaded B(1)
      field homogeneity, and the TEM coil has the best loaded B(1) field homogeneity
      and the lowest radiation loss; while the microstrip coil is better in SAR and SNR
      at 7T than the birdcage and TEM coils.

PMID- 16786581
TI  - Role for retinoid signaling in left-right asymmetric digestive organ
      morphogenesis.
AB  - The looping events that establish left-right asymmetries in the vertebrate gut
      tube are poorly understood. Retinoic acid signaling is known to impact left-right
      development in multiple embryonic contexts, although its role in asymmetric
      digestive organ morphogenesis is unknown. Here, we show that the genes for
      retinaldehyde dehydrogenase (RALDH2) and a retinoic acid hydroxylase (CYP26A1)
      are expressed in complementary patterns in the Xenopus gut during looping. A late
      stage chemical genetic assessment reveals that agonists and antagonists of
      retinoid signaling generate abnormal gut looping topologies, digestive organ
      heterotaxias, and intestinal malrotations. Accessory organ deformities commonly
      associated with intestinal malrotation in humans, such as annular pancreas,
      pancreas divisum, and extrahepatic biliary tree malformations, are also induced
      by distinct retinoid receptor agonists. Thus, late-stage retinoic acid signaling
      is likely to play a critical role in asymmetric gut tube morphogenesis and may
      underlie the etiology of several clinically relevant defects in the digestive
      system.

PMID- 16786584
TI  - Stage III cystic partially differentiated nephroblastoma recurring after
      nephrectomy and chemotherapy.
AB  - Cystic partially differentiated nephroblastoma (CPDN) has low malignant
      potential. We report a 1-year-old with stage III CPDN of the right kidney that
      recurred following radical nephrectomy and chemotherapy. There was evidence of
      tumor spillage pre-operatively and intra-operatively. During chemotherapy the
      disease recurred in the omentum and the peritoneum. Pathology of the recurrent
      resected cysts revealed a more differentiated biphasic tumor without blastemal
      elements. It appears that spillage of CPDN in our patient led to dissemination of
      disease. Chemotherapy failed to prevent recurrence but only mature elements were
      present following this treatment. The intensity of therapy required to treat CPDN
      remains undefined.

PMID- 16786583
TI  - Tensor deflection (TEND) tractography with adaptive subvoxel stepping.
AB  - PURPOSE: To develop an adaptive subvoxel stepping scheme, as an adjunct to tensor
      deflection (TEND) tractography, that automatically adjusts the stepping size by
      considering the tensor linearity to properly trace fiber bundles in regions with
      different degrees of tensor anisotropy. MATERIALS AND METHODS: A theoretical
      investigation of the TEND algorithm was performed to assess the degree of
      deflection of the propagation vector toward the major eigenvector. Mathematically
      generated phantoms (one with curved fibers and the other with crossing fibers) at
      wide ranges of signal-to-noise ratio (SNR), and human brain images obtained in
      vivo were used to test the performance of the adaptive stepping algorithm.
      RESULTS: The degree of deflection was found to be inversely related to the
      stepping size. A small stepping size was advantageous for tracing single curved
      fiber bundles, whereas a large stepping size was beneficial for passing through
      fiber crossing regions. The performance of the adaptive stepping algorithm was
      superior to fixed stepping in both situations, leading to an approximately 0.17
      voxel of deviation in curved fibers and a nearly 100% successful tracking rate in
      crossing fibers at typical SNR. Human brain images demonstrated similar results.
      CONCLUSION: The adaptive stepping algorithm is a helpful adjunct to TEND
      tractography.

PMID- 16786585
TI  - Differential expression of polycomb repression complex 1 (PRC1) members in the
      developing mouse brain reveals multiple complexes.
AB  - Polycomb group (PcG) genes are regulators of body segmentation and cell growth,
      therefore being important players during development. PcG proteins form large
      complexes (PRC) that fulfil mostly repressive regulative functions on homeotic
      gene expression. Although expression of PcG genes in the brain has been noticed,
      the involvement of PcG genes in the processes of brain development is not
      understood. In this study, we analysed the expression patterns of PRC1 complex
      members to reveal PcG proteins that might be relevant for mouse brain
      development. Using in situ hybridisation, we show PRC1 activity in proliferative
      progenitor cells during neurogenesis, but also in maturated neuronal structures.
      PRC1 complex compositions vary in a spatial and temporal controlled manner during
      mouse brain development, providing cellular tools to act in different
      developmental contexts of cell proliferation, cell fate determination, and
      differentiation.

PMID- 16786586
TI  - Defibrotide for the treatment of hepatic veno-occlusive disease in children.
AB  - BACKGROUND: This retrospective report describes experience with defibrotide in
      children with hepatic veno-occlusive disease (HVOD) following hematopoietic
      progenitor cell transplant (HPCT) in a single institution. PROCEDURE: Children
      who had undergone HPCT between February 1999 and June 2001 and between July 2003
      and September 2004 and who received defibrotide during their admission were
      identified. Demographic data and information regarding the clinical course of
      these patients were abstracted from their health records. RESULTS: Fourteen
      children (mean age: 9.3 years; range: 0.4-18.1) who underwent HPCT during the
      study period received defibrotide for the treatment of HVOD; nine were girls.
      Most patients underwent HPCT for hematologic malignancies (8/14) and received
      matched unrelated donor transplants (8/14). Conditioning regimens included
      cyclophosphamide with total body irradiation (5/14) and busulfan followed by
      cyclophosphamide (7/14). HVOD was diagnosed on transplant day -4 to +33 (median:
      +10.5); defibrotide was started on transplant day -4 to +40 (median: +12). The
      median initial defibrotide dose was 33 mg/kg/day (11-40 mg/kg/day); the median
      maximum defibrotide dose was 38.5 mg/kg/day (11-81 mg/kg/day). The median
      duration of defibrotide therapy was 16 days (4-37 days). Defibrotide was
      discontinued due to clinical improvement (9), death (3), drug unavailability (1),
      and neurological toxicity (1). Gastrointestinal hemorrhage was observed in two
      patients and intra-cranial hemorrhage was observed in one patient during
      defibrotide therapy. The survival rate to day +100 was 79%. CONCLUSIONS:
      Defibrotide appears to be an effective and relatively safe treatment for children
      with HVOD.

PMID- 16786587
TI  - Acute renal failure in a 17-year-old female with ALL receiving escalating
      intravenous methotrexate without leukovorin.

PMID- 16786588
TI  - Developmental cell death during Xenopus metamorphosis involves BID cleavage and
      caspase 2 and 8 activation.
AB  - Elimination of tadpole organs during Xenopus metamorphosis is largely achieved
      through apoptosis, and recent evidence suggest involvement of the mitochondrial
      death route and bax-initiated caspase-3 and -9 deployment. However, events
      upstream of the activation of Bax are unknown. In other models, proteins of the
      BH3-only group such as BID are known to assure this function. We show that
      Xenopus bid transcript levels increase at metamorphosis in larval cells destined
      to disappear. This increase correlates with an abrupt rise in Caspase-2 and -8
      mRNA levels and an enhanced activity of Caspase-2 and -8. In BIDGFP transgenic
      animal's tail regression is accelerated. The cleavage of BIDGFP fusion protein
      during natural or T(3)-induced metamorphosis was specifically inhibited by
      caspase-8 inhibitors. Our results show that tail regression at metamorphosis
      implicates an apoptotic pathway inducible by T(3) hormone in an organ autonomous
      manner and involving the cell death executioners BID and Caspases-2 and -8.

PMID- 16786589
TI  - Feasibility of evaluating Crohn's disease activity at 3.0 Tesla.
AB  - PURPOSE: To determine whether abdominal 3.0T MRI can be used for evaluation of
      Crohn's disease (CD) compared with ileocolonoscopy (CS), and to determine patient
      preference for MRI as opposed to CS. MATERIALS AND METHODS: Twenty patients
      scheduled for CS underwent MRI. At CS, disease severity was graded and the
      Crohn's Disease Endoscopic Index of Severity (CDEIS) was determined. Radiological
      grading (by two observers) was compared with endoscopic grading and CDEIS.
      Patient experience and preference were determined. RESULTS: In respectively 10
      (observer 1) and 13 patients (observer 2) exact agreement between radiological
      and endoscopic grading was found. In respectively 10 and 7 patients radiological
      and endoscopic grading differed one level. No statistically significant
      correlation was found between radiological grading and CDEIS. Between bowel wall
      thickness and CDEIS weak to moderate correlations were found, and between bowel
      wall enhancement and CDEIS weak correlations were found. All patients preferred
      MRI over CS. CONCLUSION: It is feasible to perform abdominal 3.0T MRI using
      orally administered contrast medium for evaluation of CD, and this method can be
      considered a patient-friendly alternative to CS.

PMID- 16786590
TI  - Automated measurement of mean wall thickness in the common carotid artery by MRI:
      a comparison to intima-media thickness by B-mode ultrasound.
AB  - PURPOSE: To determine whether the mean wall thickness (MWT) of the common carotid
      artery (CCA) measured by MRI is comparable to B-mode ultrasound (US) measurement
      of the intima-media thickness (IMT), an established marker of cardiovascular
      risk. MATERIALS AND METHODS: As part of the two-year ORION trial, 43 patients
      with 16-79% stenosis by duplex US underwent high-resolution MRI and B-mode US
      examinations of their carotid arteries. Twenty-eight carotid arteries were
      identified as having both sufficient proximal coverage and adequate image quality
      of the CCA on MRI and a corresponding US. A novel algorithm utilizing statistical
      shape modeling was developed to automatically detect and measure MWT to within
      subpixel accuracy. The interrater and interscan reproducibility of the MWT
      measurement was computed as the root-mean-square (RMS) difference. The MWT and
      IMT measurements were compared via the Pearson correlation coefficient. RESULTS:
      The MWT and IMT had a high Pearson correlation coefficient (r = 0.93; P < 0.001).
      The RMS difference between readers and between scans was 0.01 mm and 0.04 mm,
      respectively. Our automated algorithm correctly identified the lumen in 28 cases
      (100%) and the outer-wall boundary in 26 cases (93%). CONCLUSION: Automated
      measurements of the MWT by MRI are reproducible and have a high correlation with
      the IMT by B-mode US.

PMID- 16786591
TI  - Optimized cationic lipid-based gene delivery reagents for use in developing
      vertebrate embryos.
AB  - We have used cationic lipid-based transfection reagents for ectopic gene
      expression experiments in developing vertebrate embryos. Lipofectamine,
      Lipofectamine 2000, and Lipofectamine enhanced with a disulfide linked pegylated
      lipid (mPEG-SS-DOPE) were initially tested and optimized in cell culture. Two
      reagent formulations, 1:4 (DNA:Lipofectamine 2000) Lipofectamine 2000, and 7.5%
      pegylated Lipofectamine, produced the highest levels of gene expression in vitro.
      Those formulations, containing the enhance green fluorescent protein reporter
      gene, were microinjected into intact vertebrate embryos -- systemically through
      the vasculature and locally into selected tissues -- to assess in vivo
      transfection efficiency. Whereas both formulations are capable of transfecting
      cells in developing embryos in vivo, greater transfection efficiencies in a
      broader range of tissue types were obtained with the pegylated Lipofectamine
      formulation. We conclude that in developing vertebrate embryos, optimized
      cationic lipid-based reagents are capable of producing significant levels of
      ectopic gene expression and can be used as alternatives to electroporation and
      viral-mediated gene delivery.

PMID- 16786592
TI  - Restricted expression of Fgf16 within the developing chick inner ear.
AB  - Fibroblast growth factor (FGF) signaling is required for otic placode induction
      and patterning of the developing inner ear. We have cloned the chick ortholog of
      Fgf16 and analyzed its expression pattern in the early chick embryo. Expression
      is restricted to the otic placode and developing inner ear through all the stages
      examined. By the closed otocyst stage, expression has resolved to anterior and
      posterior domains that partially overlap with those of bone morphogenetic protein
      4 (Bmp4), a marker of the developing sensory patches, the cristae of the anterior
      and posterior semicircular canals. Platelet-derived growth factor alpha (PDGFA),
      another growth factor with restricted otic expression, also overlaps with Fgf16
      expression. The restricted expression pattern of Fgf16 suggests a role for FGF
      signaling in the patterning of the sensory cristae, together with BMP signaling.

PMID- 16786594
TI  - Mathematical model of morphogen electrophoresis through gap junctions.
AB  - Gap junctional communication is important for embryonic morphogenesis. However,
      the factors regulating the spatial properties of small molecule signal flows
      through gap junctions remain poorly understood. Recent data on gap junctions, ion
      transporters, and serotonin during left-right patterning suggest a specific
      model: the net unidirectional transfer of small molecules through long-range gap
      junctional paths driven by an electrophoretic mechanism. However, this concept
      has only been discussed qualitatively, and it is not known whether such a
      mechanism can actually establish a gradient within physiological constraints. We
      review the existing functional data and develop a mathematical model of the flow
      of serotonin through the early Xenopus embryo under an electrophoretic force
      generated by ion pumps. Through computer simulation of this process using
      realistic parameters, we explored quantitatively the dynamics of morphogen
      movement through gap junctions, confirming the plausibility of the proposed
      electrophoretic mechanism, which generates a considerable gradient in the
      available time frame. The model made several testable predictions and revealed
      properties of robustness, cellular gradients of serotonin, and the dependence of
      the gradient on several developmental constants. This work quantitatively
      supports the plausibility of electrophoretic control of morphogen movement
      through gap junctions during early left-right patterning. This conceptual
      framework for modeling gap junctional signaling -- an epigenetic patterning
      mechanism of wide relevance in biological regulation -- suggests numerous
      experimental approaches in other patterning systems.

PMID- 16786593
TI  - Determination of dihedral Psi angles in large proteins by combining
      NH(N)/C(alpha)H(alpha) dipole/dipole cross-correlation and chemical shifts.
AB  - We propose a strategy based on the combination of experimental
      NH(N)/C(alpha)H(alpha) dipole/dipole cross-correlated relaxation rates and
      chemical shift analysis for the determination of Psi torsion angles in proteins.
      The method allows the determination of a dihedral angle that is not easily
      accessible by nuclear magnetic resonance (NMR). The measurement of dihedral angle
      restraints can be used for structure calculation, which is known to improve the
      quality of NMR structures. The method is of particular interest in the case of
      large proteins, for which spectral assignment of the nuclear Overhauser effect
      spectra, and therefore straightforward structural determination, is out of reach.
      One advantage of the method is that it is reasonably simple to implement, and
      could be used in association with other methods aiming at obtaining structural
      information on complex systems, such as residual dipolar coupling measurements.
      An illustrative example is analyzed in the case of the 30-kDa protein 6
      phosphogluconolactonase.

PMID- 16786595
TI  - STRUCTFAST: protein sequence remote homology detection and alignment using novel
      dynamic programming and profile-profile scoring.
AB  - STRUCTFAST is a novel profile-profile alignment algorithm capable of detecting
      weak similarities between protein sequences. The increased sensitivity and
      accuracy of the STRUCTFAST method are achieved through several unique features.
      First, the algorithm utilizes a novel dynamic programming engine capable of
      incorporating important information from a structural family directly into the
      alignment process. Second, the algorithm employs a rigorous analytical formula
      for profile-profile scoring to overcome the limitations of ad hoc scoring
      functions that require adjustable parameter training. Third, the algorithm
      employs Convergent Island Statistics (CIS) to compute the statistical
      significance of alignment scores independently for each pair of sequences.
      STRUCTFAST routinely produces alignments that meet or exceed the quality obtained
      by an expert human homology modeler, as evidenced by its performance in the
      latest CAFASP4 and CASP6 blind prediction benchmark experiments.

PMID- 16786596
TI  - Solution structure of TA1092, a ribosomal protein S24e from Thermoplasma
      acidophilum.

PMID- 16786597
TI  - Collagen fibril assembly during postnatal development and dysfunctional
      regulation in the lumican-deficient murine cornea.
AB  - The transparent cornea is the outer barrier of the eye and is its major
      refractive surface. Development of a functional cornea requires a postnatal
      maturation phase involving development, growth and organization of the stromal
      extracellular matrix. Lumican, a leucine-rich proteoglycan, is implicated in
      regulating assembly of collagen fibrils and the highly organized extracellular
      matrix essential for corneal transparency. We investigated the regulatory role(s)
      of lumican in fibril assembly during postnatal corneal development using wild
      type (Lum+/+) and lumican-null (Lum-/-) mice. In Lum+/+ mice, a regular
      architecture of small-diameter fibrils is achieved in the anterior stroma by
      postnatal day 10 (P10), while the posterior stroma takes longer to reach this
      developmental maturity. Thus, the anterior and the posterior stroma follow
      distinct developmental timelines and may be under different regulatory
      mechanisms. In Lum-/- mice, it is the posterior stroma where abnormal lateral
      associations of fibrils and thicker fibrils with irregular contours are evident
      as early as P10. In contrast, the anterior stroma is minimally perturbed by the
      absence of lumican. In Lum+/+ mice, lumican is expressed throughout the
      developing stroma at P10, with strong expression limited to the posterior stroma
      in the adult. Therefore, the posterior stroma, which is most vulnerable to
      lumican-deficiency, demonstrates an early developmental defect in fibril
      structure and architecture in the Lum-/- mouse. These defects underlie the
      reported increased light scattering and opacity detectable in the adult. Our
      findings emphasize the early regulation of collagen structure by lumican during
      postnatal development of the cornea.

PMID- 16786598
TI  - Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in
      patients with adult T-cell leukemia.
AB  - Here, we report that freshly isolated unstimulated adult T-cell leukemia (ATL)
      cells present high telomerase activity compared to asymptomatic carriers or
      normal donors. In spite of this high telomerase activity, ATL cells retained
      shorter telomeres compared to those of uninfected cells isolated from the same
      patients. Because the safeguarding of telomere length is critical to the
      unlimited proliferation of tumor cells, we investigated the underlying mechanism
      for short telomere maintenance in ATL cells. Transcriptional and
      posttranscriptional expression of telomere-binding proteins TRF1, TRF2, TIN2 and
      POT1, known to regulate telomere homeostasis and protection, were evaluated. We
      found that TRF1 and TRF2 are overexpressed in in vivo patient's samples from ATL
      but not asymptomatic carriers, while levels of POT1 expression did not
      specifically increase in ATL. To gain insights into the regulation of TRF genes
      in HTLV-I infected cells, we investigated the expression of TIN2, a regulator of
      these genes, and found an increase in TIN2 expression in ATL patients. Together
      our results underscore the importance of telomerase and telomere length
      regulating factors as novel markers for ATL disease progression and as potential
      therapeutic targets for the treatment of HTLV-I-associated malignancies.

PMID- 16786599
TI  - Molecular simulations reveal a new entry site in quercetin 2,3-dioxygenase. A
      pathway for dioxygen?
AB  - Molecular dynamics simulations performed on quercetin 2,3-dioxygenase have shown
      the existence of a channel linking the bulk solvent and the cavity of the enzyme.
      Although much is known about the the oxygenolysis reaction catalyzed by this
      enzyme, the way dioxygen enters the active site has not been firmly established.
      The size, orientation and hydrophobic character of this channel suggests that it
      could provide an entrance for molecular dioxygen into the cavity. Free energy
      calculations show that such a process is likely to occur.

PMID- 16786600
TI  - Old fold in a new X-ray diffraction dataset? Low-resolution molecular replacement
      using representative structural templates can provide phase information.
AB  - The advent of structural genomics has led to a dramatic increase in the number of
      structures deposited in the Protein Data Bank. The number of new folds, however,
      still remains a very small fraction of the total number of deposited structures.
      Recent data on the progress of the structural genomics initiative reveals that
      more than 85% of target proteins that progress to the stage of data collection
      and structure determination have a known fold. Enzymes, which tend to exploit
      reaction space while adopting a common stable scaffold, contribute significantly
      to this observation. Herein, we evaluate a method to examine the "old fold in a
      new dataset" scenario likely to be encountered in the structural genomics
      pipeline. We demonstrate that a fold detection strategy based on secondary
      structure signatures followed by molecular replacement using a minimalist model
      can be effectively used to solve the phase problem in X-ray crystallography
      without further recourse to heavy atom derivatives or multiple anomalous
      dispersion techniques. Three common folds-the triosephosphate isomerase (TIM),
      adenine nucleotide alpha hydrolase-like (HUP), and RNA recognition motif (RRM)
      were examined using this approach. The results presented herein also provide an
      estimate of the extent of phase information that can be derived from a single
      domain in a large multidomain structure.

PMID- 16786601
TI  - An amylase/Cre transgene marks the whole endoderm but the primordia of liver and
      ventral pancreas.
AB  - Mice bearing a Cre-encoding transgene driven by a compound [SV40 small t
      antigen/mousealpha-amylase-2] promoter expressed the recombinase at early
      developmental stages broadly in the embryonic endoderm before the pancreas and
      lungs begin to outgrow, but not in other germ layers, as determined indirectly by
      beta-galactosidase and YFP reporter activity, indicating that the transgene is in
      fact an endodermic marker. Interestingly, the liver and ventral pancreas were
      excluded from this expression pattern, denoting that the chimerical alpha-amylase
      2 promoter was not active in the anterior leading edge of the endoderm (the
      presumptive region from which liver and ventral pancreas form). These transgenics
      thus confirm, among other findings, that dorsal and ventral pancreatic primordia
      have different intrinsic transcriptional capabilities. In conclusion, we have
      generated a new transgenic mouse that should be useful to target endoderm at
      early stages, without affecting the liver or ventral pancreas before embryonic
      day E12.5.

PMID- 16786602
TI  - Resection of selected invasive squamous cell carcinoma of the pyriform sinus by
      means of the lateral pharyngotomy approach: the partial lateral pharyngectomy.
AB  - BACKGROUND: Although the lateral pharyngotomy is a well-known surgical procedure,
      to our knowledge, no published reports have described the results achieved with a
      lateral pharyngectomy approach in patients with isolated and previously untreated
      selected invasive squamous cell carcinoma of the lateral wall of the pyriform
      sinus. METHODS: The medical files and operative charts of 30 patients with an
      isolated, and previously untreated, squamous cell carcinoma of the pyriform
      sinus, treated for cure by lateral partial pharyngectomy and primary closure, as
      well as postoperative radiotherapy (n = 22), and preoperative chemotherapy (n =
      8), were retrospectively studied. Sixteen tumors were classified as T1 and 14 as
      T2. All patients but one were followed until death. RESULTS: Three patients (9%)
      died in the immediate postoperative period (two from medical complications and
      one from a surgery-related complication). Overall, 29 patients died, resulting in
      a 77.7%, 40%, 23.3%, and 15% 1-, 3-, 5- and 10-year Kaplan-Meier actuarial
      survival estimate, respectively. Only one patient had a serious postoperative
      complication develop. All patients were decannulated. No patients required a
      gastrostomy and/or completion total laryngectomy for functional reasons. Local
      recurrence occurred in four patients (13%). The 3-and 5-year Kaplan-Meier
      actuarial local control estimates were 88.5% and 79.6%, respectively. The use of
      a platin-based induction chemotherapy (p = .05) regimen was the only variable
      that was significantly statistically related to local recurrence. Overall, a
      93.3% laryngeal preservation rate was achieved. CONCLUSION: Partial pharyngectomy
      by means of the lateral pharyngotomy combined with postoperative radiation
      therapy is an efficient and function-sparing approach to control selected
      invasive squamous cell carcinomas of the lateral wall of the pyriform sinus.

PMID- 16786603
TI  - Outbreak news. Cholera, Angola--update.

PMID- 16786605
TI  - Health crisis worsens in Central African Republic.

PMID- 16786604
TI  - US physician-senator Bill Frist disappoints on health.

PMID- 16786607
TI  - LTC facilities struggle to solve Part D problems.

PMID- 16786606
TI  - Britain's postdocs unite.

PMID- 16786608
TI  - MI: nurse practictioner's affidavit of merit: sufficient only as 'prerequisite'
      to filing suit.

PMID- 16786609
TI  - [Nikolai Vasil'evich Lazarev (110-th anniversary of his birth)].

PMID- 16786611
TI  - Australia's impaired glycaemic function.

PMID- 16786610
TI  - Letters and notes in orthopaedic surgery.
AB  - INTRODUCTION: Accurate written communication is essential in orthopaedic surgery.
      Incomplete and poorly structured letters can lead to poor knowledge of a
      patient's diagnosis. MATERIALS AND METHODS: Structured and traditional letter
      formats were compared for speed of reading and preference by general
      practitioners (GPs), consultants, registrars and out-patient nursing staff. In
      addition, out-patient clinic letters and notes were analysed and compared for
      speed of reading and ease of assimilating information and content. RESULTS: There
      was overwhelming preference for the structured letter format. This style of
      letter could be read significantly more quickly with information better
      assimilated and relevant data included more frequently. However, only 26% of
      letters generated contained a complete set of information sought by GPs and
      hospital staff. CONCLUSIONS: Structured letters are better in orthopaedics
      because it is easier to access the contents. The structured format disciplines
      medical staff to address essential information. Even with a structured format the
      majority of letters omitted essential information. Training in letter writing is
      necessary. A structured letter format next to dictating machines might improve
      the quality of letters generated.

PMID- 16786612
TI  - Global ecosystem at risk.

PMID- 16786613
TI  - Climate change and health: is there a risk?

PMID- 16786614
TI  - [121st Internal Medicine Seminar--XXVI Vanysek Seminar held on the anniversary of
      the birth of Dr. Rudolf Vanysek, the founder of Internal Medicine in Brno. Friday
      15 March 2002, Brno. Inflammatory diseases of the pancreas].

PMID- 16786615
TI  - ACCF issues consensus report on CAM.

PMID- 16786616
TI  - Connecting passions: medical students and teachers  in paediatrics.

PMID- 16786617
TI  - Student attitudes towards the doctor-patient  relationship in a medical college
      in western Nepal.

PMID- 16786618
TI  - The taint of 'misbehavior'.

PMID- 16786619
TI  - Consequences of sex selection.

PMID- 16786620
TI  - Blood feud: a controversy over South American DNA samples held in North American
      laboratories ripples through anthropology.

PMID- 16786621
TI  - An activist group's hidden-camera investigation at Chapel Hill raises issues
      about college's oversight of animal welfare.

PMID- 16786622
TI  - Joint Commission expectations related to USP-NF Chapter 797 on compounding
      sterile preparations.

PMID- 16786623
TI  - [Microbial biotechnologies: scientific aspects and implementation conditions].

PMID- 16786625
TI  - [On the nature of the pathogen of pale-green dwarfism in cereals].
AB  - The paper presents more precise data concerning optimal temperature demands to
      growth of white-yellow dwarfness of cereals (WYDC) identified before as
      Acholeplasma laidlawii var. granulum, its relation to sterols and genome
      properties was determined using pulse-electrophoresis. It was established that
      the agent strains 84 and 118, characterized by phytopathogenicity, grew most
      intensively at 32 degrees C; they behaved as mesoplasmas but, as it had been
      found, they were capable to synthesis of carotenoids and displayed close
      serologic affinity for A. laidlawii PG8. That is, the above strains are typical
      acholeplasmas capable to live in leafhoppers which carry a disease and in cereals
      plants and cause a disease with typical symptoms of "yellows" in the latter.
      Molecular weight of the strain 84 genome was 2200 t.p.n. (GC = 33 mol %); in
      strains 118 it was 2310 t.p.n. (GC = 34.2 mol %). Allowing for the fact that
      molecular weight of genome of A. laidlavii var. granulum is almost by 1/3 (1600 +
      710 t.p.n.) more than that of A. laidlawii PG8 genome, the authors think that the
      agent of WYDC is the evolution precursor (or one of precursors) which initiated
      the Acholeplasma and Phytoplasma genera as a results of splitting of their
      genomes.

PMID- 16786624
TI  - [Shewanella genus bacteria isolated from the Black sea water and molluscs].
AB  - Six (6) strains of bacteria isolated from the Black Sea water and mollusks
      Mytilaster lineatus have been assigned to Shewanella genus on the basis of
      phenotypical and molecular-genetic study. Partial sequence of 16S rRNA gene
      revealed 100% similarity of three of these strains to S. baltica, although they
      had some phenotypical differences. Three more strains were genetically related to
      S. colwelliana and S. affinis (99-100% of 16S rRNA sequences similarity), but
      they differed from these species as well as from each other in some phenotypical
      properties, so the question about their taxonomic status still remains open. In
      aerobic conditions the Black Sea strains of S. baltica adsorbed significant
      quantities of Fe III from the media. They reduced it to Fe (II) in anaerobic
      conditions. Strains isolated from mollusks were not able to reduce Fe (III).

PMID- 16786626
TI  - [Alpha-amylases of Bacillus subtilis].
AB  - Preparations of alpha-amylase have been obtained as a result of screening of
      Bacillus subtilis strains. They can hydrolyse starch at a temperature from 60 to
      95 degrees C at acidic and alkaline values of pH and hold stability during 2-3
      hours. Alpha-Amylase of B. subtilis 147 with optimum pH 9.1 which displayed
      activity at 95 degrees C, proved to be promising for further investigations,
      since it is competitive with the already described alpha-amylases of Bacillus.

PMID- 16786627
TI  - [Expression of genes of prophage P1 Escherichia coli in cells of phytopathogenic
      Erwinia].
AB  - It is shown that the temperate coliphage P1Cmcts100 can transduce resistance to
      chloramphenicol in the cells of phytopathogenic bacteria Erwinia horticola and E.
      carotovora subsp. atroseptica. In the latter case the extrachromosomal DNA is
      inherited by recipient cells as the authentic prophage P1. The prophage P1
      expresses rectification-modification EcoP1, as well as the genes of lysogenic
      conversion in phytopathogenic erwinia. Here the character of superinfection of
      transductants of E. atroseptica g125 by erwiniophage ZF40, by certain
      carotovoricines and coliphage T21 changes. Besides, the expression of genes of
      prophage P1 leads to the increase of survival of E. atroseptica when raising the
      environment temperature. Under these conditions the trans mutagenesis of
      bacterial chromosome can precede, that permits considering the phage P1 as a
      special tool for studying the molecular genetics of erwinia.

PMID- 16786628
TI  - [Effect of exogenous plasmid R68.45 on productive and lisogenic development of
      temperate bacteriophage ZF40 Erwinia carotovora].
AB  - The Erwinia carotoerora strains bearing exogenous plasmid R68.45 have been
      obtained by means of transconjugation. Dynamics and frequency characteristics of
      plasmid transfer to erwinia cells have been studied. Plasmid-phage interrelations
      have been studied for the first time in E. carotovora. It has been established
      that the presence of exogenous plasmid R68.45 affects essentially the culture
      growth parameters and lisogenization of E. carotovora by the wild phage ZF40 and
      its clear-mutants. The phage infection leads to the exclusion of plasmid R68.45
      with different frequency (from 23 to 45% depending on the phage mutant). The
      presence of plasmid R68.45 in the erwinia cells destabilizes the defective
      lysogeny in E. carotovora.

PMID- 16786629
TI  - [Peculiarities of growth and development of strains Hormoconis resinae (Lindau)
      V. arx & De Vries F. Resinae and Cladosporium sphaerospermum penz].
AB  - The work deals with the effect of limitation of organic carbon (glucose) on the
      growth and morphology of two species of microscopic fungi Hormoconis resinae and
      Cladosporium sphaerospermum (11 strains), isolated from premises of the 4th unit
      of the Chernobyl NPP and isolation places which arc pure from radionuclides. The
      dissimilar reaction of each of the species to decreasing the amount of organic
      carbon in the culture medium has been established. Ontogenesis reduction was
      observed for both species under the conditions of limitations of organic carbon.
      In was manifested for H. resinae in reduction of the typical conidial sporulation
      and in transition to micelial way of existence, and only conidial sporulation and
      formation of "empty" micelium Were registered under such conditions for C.
      sphaerospermum. The studied strains were related to 3 ecologic groups by
      oligocarbotolerance criterion: typical saprotrophs, intermediate group, strains
      with a tendency to oligocarbotolerance.

PMID- 16786630
TI  - [Functional properties of prosomal protein 39 kappaDa from Datura stramonium
      leaves infected with Potato Virus X].
AB  - Free cytoplasmic informosomes isolated from Datura stramonium plants infected by
      PVX contain a low-molecular ribonucleoprotein complex (RNP). This complex as to
      its main physico-chemical parameters (sedimentation coefficient 10S, buoyant
      density in CsSO4 1.31 g/cm3, stability to 1% lauroylsarcosinate-Na) corresponds
      to the prosome (inhibitory RNP). Prosomes isolated from free mRNP of D.
      stramonium plants infected by PVX contain the protein of 39 kDa. This protein was
      shown to be capable to phosphorylate in vitro in the composition of informosomes
      and prosomes. It is possible that this protein can be the protein-repressor,
      since it is absent in the translated polysome-associated form of mRNP. The label
      incorporation has shown that the protein of 39 kDa is able to reduce in vitro the
      template activity of genomic RNA PVX to 40% and RNA TMIV--to 30%. Moreover, the
      protein 39 of kDa has the protease activity. It affects substrate-case in like
      trypsin. It is supposed that it can participate in splitting the intracellular
      proteins as well as in the expression of the virus genome, it can also influence
      the template activity of cell RNAs.

PMID- 16786631
TI  - [Research of modulation of CD95-mediated apoptosis in lymphoblastic MP-1 and BJAB
      cells infected by adenovirus and Epstein-Barr virus].
AB  - Model systems of infecting limphoblastic MP-1 and BJAB cells by Epstein-Barr
      virus, 5 serotype adenovirus and double infection are developed. A rather high
      level of accumulation of DNA of these viruses in the cells in dynamics at
      monoinfection and inhibition interference at multi-infection was shown by PCR
      method. The influence of virus infection on proliferative activity was studied.
      The stimulation of cells growth in the system BJAB + EBV was detected, and double
      infecting inhibited the process by 50%. The 25% difference in development of
      apoptosis process between cells infected by adenovirus and EBV was established
      when defining CD95-mediated apoptosis in infected MP-1 cells. The infecting of
      BJAB cells by viruses had a scarce effect on the processes of spontaneous
      apoptosis, but the data on CD95-mediated apoptosis at EBV infection testify to
      inhibition of this process both at a monoinfection, and at a double infection.
      The work was performed in the framework of the fundamental agreement of Ministry
      of Education and Science of Ukraine F7/366-2001, and grant INTAS N011-2382.

PMID- 16786632
TI  - [Study of some properties of strain Lactobacillus plantarum G3/3(13) antagonistic
      factor].
AB  - The screening of strains which expressed antagonistic activity, that is not
      connected with lactic acid and hydrogen peroxide synthesis was conducted among 72
      cultures of lactic acid bacteria. The strain L. plantarum G3/3(13) which
      inhibited growth of 11 test-cultures including Lactobacillus plantarum,
      Enterococcus faecalis and E. faecium was selected. The antibacterial factor was
      of protein nature, did not retain the activity after boiling and was active at pH
      2.0-8.0, whereas at pH 9.0 its activity fell significantly. The obtained results
      allow to assume that the formed agent can be bacteriocin-like substance and the
      strain L. plantarum G3/3(13) may be useful for food industry or probiotic
      construction.

PMID- 16786633
TI  - [Study of vaginal and intestinal microflora of women in the prenatal period and
      its correction in dysbacteriosis].
AB  - A comparative research of the structure of vaginal and intestinal microflora in
      norm and at kidney pathologies in women in the prenatal period was carried out.
      At physiologically normal course of pregnancy microbiocenosis of vagina and
      intestine does not contain pathogenic and conditional-pathogenic microorganisms.
      Lactic acid bacteria are fixed within the limits of 10(5)-10(8) CFU/1 ml in the
      vagina secretion and 10(7)-10(8) CFU/1 g in the intestine content. The spore
      microorganisms have completely disappeared in vaginal biocenosis of women with
      pyelonephritis after pharmacotherapy; and colibacterias has disappeared in 62% of
      women. Quantity of lactic acid bacteria has also decreased. Quantity of E. coli
      (10(8)- 10(9)) CFU/g, sporous microorganisms (10(3)-10(4)) CFU/g and yeast (10(4)
      10(5)) CFU/g has considerably increased in the content of intestine. Lactic acid
      bacteria in content of the vagina are presented by: Lactobacillus acidophilus, L.
      plantarum, L. fermentum, L. vaginalis; in content of the intestine--L. plantarum
      and L. fermentum. All the isolated strains of lactobacilli are resistant to
      metrogyl and amphotericin, 87%--to cephoxitine, cypropfloxacine. Twenty three of
      24 strains of lactic acid bacteria--antagonists of pathogenic microflora have
      shown adhesion to vaginal epthelium. The degree of adhesive activity depends on
      the strain and genus specificity of cultures. The highest index of adhesiveness
      in indicated in Enterococcus faecium (5.82 - 7.62) and Streptococcus salivarius
      subsp. thermophilus (2.74 - 6.40) strains. The screening of strains has been
      performed, which suppress growth of gas-producing microflora. The strain of
      Lactobacillus plantarum 200D proved to be the most active one. A complex of
      cultures of the lactic bacteria providing normalization of microbial cenosis of
      the vagina in women in the prenatal period has been selected as based on the data
      obtained. The biotechnology of production of vaginal suppositories is developed.

PMID- 16786634
TI  - [Fusariosis of seeds of winter triticale].
AB  - The results of studying the mycoflora of winter triticale grains and seedlings
      after artificial and natural inoculation are presented. The species of Fusarium,
      Alternaria, Helminthosporium, Septoria, Cladosporium, Penicillium, Rhizopus were
      identified. Fusarium spp., prevailed over other fungi as to the number of its
      isolates. Its isolates (n = 142) were distinguished, 5 species were identified.
      It is significant, that most isolates of Fusarium graminearum caused a disease of
      grains. The species F. oxysporum dominated on winter triticale seedlings.

PMID- 16786635
TI  - [Psychiatric care act of Ukraine and issues concerning reformation of the mental
      health protection service].
AB  - An analysis was performed of the conception and content of a new Psychiatric Care
      Act by making a comparison with data from published literature and the present
      day status of the mental health protection service. The main features of the
      crisis of psychiatry in Ukraine are characterized together with possible ways of
      resolving it. Main trends in reformation of the psychiatric service are
      identified that are to be secured by relevant acts of departmental and
      interdepartmental character based on law. Priority is emphasized to defence of
      the patients' rights and liberties together with a need for a guarantee of a
      highly skilled medical care to be provided for mental patients.

PMID- 16786636
TI  - [Pharmacotherapy of intestinal dysbacteriosis].
AB  - The article presents a summary of the published literature together with results
      of the author's own investigations designed to study pharmacotherapy of
      intestinal dysbacteriosis. Reasons for the origination of the above medical
      condition are given, the particulars of its clinical presentation are specified.
      Clinical-and-pharmacological properties of chylac forte, a new effective
      probiotic, are detailed.

PMID- 16786637
TI  - [Immunity status in persons with acute radiation disease].
AB  - Following the Chernobyl accident those persons having survived acute radiation
      sickness demonstrated significant decline in the activity of myeloperoxidase in
      the peripheral blood neutrophilic granulocytes, which fact results in a decrement
      of bactericidial power of cells. The neutrophilic granulocyte peroxidase activity
      can hardly ever be referrable to the intensity of oxidative processes in them,
      which fact is an intriguing issue warranting further study. In analyzing
      parameters characterizing cell-bound immunity in patients late after the accident
      persistent changes are recordable in the CD4+ / 8+ ratio. The humoral link of
      immunity was found to be more labile. We failed to find out established
      regularities in its abnormalities.

PMID- 16786638
TI  - [Epidemiological study on special features of prevalence of disorders of the
      endocrine system among rural population living in different ecological
      conditions].
AB  - An epidemiological study was made on special features of prevalence of disorders
      of the endocrine system among the rural population over the period 1992-1996
      based upon 8 regions of Ukraine. The role has been ascertained of ecological
      factors in modification of contingent prevalence of endocrine diseases. A
      hypothesis has been framed that there is the "exposure-->effect" type
      relationship between abnormal levels of radiation contamination and risk for
      origination of disorders of the endocrine system and increase in endocrine
      morbidity.

PMID- 16786639
TI  - [Lymphocyte changes in ischemic heart disease].
AB  - The paper focuses on the membrane lipid complex status and lymphocyte metabolic
      activity in IHD patients to elaborate new approaches toward treatment and
      prevention of immune disorders in the above pathology. The study was made in
      blood specimens from 53 coronary patients presenting with progressive unstable
      angina. The diagnosis was made on the basis of a complex clinical-and-laboratory
      and electrocardiographic evaluation. The composition of the lymphocyte membrane
      lipid complex and blood serum was studied with the aid of the gas chromatography
      techniques. Three variants were identified of change in the lipid composition of
      lymphocyte membranes in IHD patients having undergone the above evaluation. We
      consider it expediant to use criteria for the state of lymphocyte membranes in
      IHD patients in order that we might properly deal with issues concerning
      diagnosis, prognosis and selection of optimum pathogenetic therapy of the medical
      condition in question.

PMID- 16786640
TI  - [Effects of exogenous cholesterol on the functional morphology of blood formed
      elements in atherogenesis dynamics].
AB  - Results of clinical and experimental studies showed that exogenous cholesterol is
      a factor of initiation of athero- and thrombogenesis that under conditions of
      failure of compensatory reactions are manifested by generation and progression of
      illness. In the control group of observation, activation of leukocytes in
      indicative of reciprocal reactions of cell-bound immunity directed to elimination
      of atherogenic lipoproteids whereas in patients with ischemic heart disease, the
      cholesterol load apparently provokes cell type effector reactions leading to
      damage to and necrosis of cells. In healthy subjects, chemotaxis and phagocytosis
      become activated while in sick persons they get supressed. We can well believe
      that there takes place fixation of an antigen (in the given case--apo-beta
      lipoproteins) on macrophages and polymorphonuclear leukocytes with subsequent
      cascade to follow such as activation of lipooxygenase, active forms of oxygen,
      superoxydes, cytokins, as well as production of elastase and collagenase, which
      fact in the presence of a high degree inter-cellular cooperation results in
      formation of a vicious circle. The findings secured corraborate etiological
      significance of exogenous cholesterol and saturated fatty acids as a starting
      point of atherogenesis.

PMID- 16786641
TI  - [Interrelation between levels of eicosanoids and tachykinins in the expired air
      condencate in the obstructive type respiratory insufficiency in patients with
      destructive pulmonary tuberculosis].
AB  - The content was studied of vasoactive intestinal peptide (VIP), substantia P
      (SP), bombesine (BMB), prostaglandins (PG) E2, F2alpha, 6-keto-F1alpha, Tx A2,
      and leukotrien (LT) B4 in the expired air condensate with the aid of the
      radioimmune technique to reveal a relation between pulmonary tachykinins and
      eicosanoids in obstructive type respiratory incompetence in patients with
      pulmonary tuberculosis. In patients with pulmonary tuberculosis, a high level of
      BMB was measurable in the expired air condensate. A linear negative correlation
      has been established between BMB content and forced expiratory volume, SP and
      respiratory volume, SP and lung capacity. In pulmonary tuberculosis, PGE2 and
      PGF2alpha levels are significantly evaluated. There was a positive correlation
      between BMB content and PGF2a in the expired air condensate, which fact suggests
      their synergic action on the smooth muscles of the bronchi and bronchioles.

PMID- 16786643
TI  - [Hemocoagulation disorder and its impact on cerebral hemodynamics in patients
      with type I diabetes mellitus].
AB  - Indices were studied for the blood coagulation system in 132 patients with
      insulin-dependent diabetes mellitus (IDDM). The above indices tended to change
      toward hypercoagulation. The degree of changes was found to be related to
      duration and severity of illness. Patients presenting with a grave form DM more
      than 10 years in duration demobnstrated changes in their coagulograms suggesting
      the development of the chronic disseminated intravascular coagulation syndrome.
      Correlation has been established between fibrinogen and indices of
      reoencephalogram reflecting the state of the cerebral vascular system. The
      conclusion reached was to the effect that hyperfibrinogenemia makes for reduction
      in the brain pulse blood, is related to the development of venous discirculation,
      increase in the rigidity of cerebral vessels and heterogenuity of the blood
      filling in the brain.

PMID- 16786642
TI  - [Effects of alcoholic beverages on the fatty acid spectrum of the expired air
      condensate lipids in patients with tuberculosis of the respiratory organs].
AB  - Results are highlighted of the study into the pulmonary surfactant in healthy
      subjects. as well as in those afflicted with pulmonary tuberculosis who abused
      alcoholic drinks, with the aid of the chromotography techniques. It has been
      ascertained that activity of the pulmonary surfactant is dependent upon the
      clinical form of tuberculosis, its extension and presence of alcoholism. The
      lipid polyunsaturated fatty acids, with the linoleic (C18:2) and arachidonic
      (C20:4) acids being the most sensitive ones to the process of lipid peroxidation
      (LPO), and the study into the spectrum of lipid fatty acids in the expired air
      consensate suggest intencity of LPO in the pulmonary surfactant and permit
      carrying out its correction in a timely fashion during the process of treatment.

PMID- 16786644
TI  - [Metabolic indices for the bone tissue organic base metabolism and its mineral
      metabolism in patients with scoliosis].
AB  - The biochemical findings secured in the examination of 55 pediatric patients
      presenting with a progressing form of scoliosis suggested to us abnormalities of
      metabolism in the osseous tissue organic base and of the mineral metabolism.
      Indices capable of reflecting in the most unbiassed fashion the osseous tissue
      metabolic states include Ca/Cr, Ca/fr OP, Ph/Cr, Ph/fr OP ratios. Collagen and
      mineral metabolic disturbances result in structural changes in the vertebral
      osseous tissue organic base that may have an important part in the development of
      scoliotic disease.

PMID- 16786645
TI  - [Separate catheterization test in the assesment of the kidney function in
      patients with renal artery stenosis].
AB  - An investigation has been designed to study the functional state of the kidneys
      in arterial affection of the major trunk by studying indices for separate
      catheterization of the ureters in 24 patients presenting with the functionally
      significant stenosis and 21 patient with essential hypertension. It has been
      established that significance of classical criteria of assessment of separate
      catheterization tests comes up to 45.2%, semi-classical 70.2%. Strong
      lateralization of the indices in three collections of urine secures the
      diagnostic usefulness of the study in 95.2% of cases.

PMID- 16786646
TI  - [Diagnostic significance of certain cellular immune system disorders in children
      with Perthes disease].
AB  - Data are submitted to the effect that parameters associated with the cell link of
      the immune system should allow some judgement about character and degree of time
      related immunological abnormalities in children with Perthes disease. In the
      earliest stages of the illness immunological abnormalities are in large measure
      related to the presence of foci of chronic bacterial infection as evidenced by a
      high NBT-test. The above immunological abnormalities aggravate the course of
      aseptic necrosis of the hip joint or they serve as a trigger mechanism of its
      development.

PMID- 16786647
TI  - [Osteosynthesis of the femoral neck fractures using the original device].
AB  - At the centre of traumatology, the Central District Clinical Hospital N 12 of
      Kiev, the authors have conducted investigations in order that on the basis of
      clinical and roentgenologic findings they might assess both early and long-term
      results of osteosynthesis of the femoral neck fractures with the aid of the
      elaborated device made of titanium. The studies were made in 43 patients aged 30
      to 70 years over the period 1997-2000. Complications were recorded in 9.5 percent
      of cases. Osteosynthesis of the femoral neck fractures by making use of the
      elaborated device will, we believe, come to be efficiently used by
      traumatologists.

PMID- 16786648
TI  - [Effect of chondroprotectors in the treatment and prophylaxis of the knee joint
      osteoarthrosis].
AB  - An analysis is presented of employment of hyalgan (1% solution of hyaluronic
      acid) in 29 patients with osteoarthrosis of the knee joint (KJOA). The patients
      were divided into three groups. Group I comprized 9 patients with prior
      arthroscopic interventions in the knee joint with stage I KJOA; group II was 5
      patients having undergone plasty of the anterior cruciate ligament with stage I
      KJOA; group III was 15 patients with stage II-III KJOA. Hyalgan (20 mg) was
      administered once per week for 5 weeks. Intensity of the pain syndrome was
      assessed by using a visual-analogue scale together with time-related thermal
      gradient with the aid of the remote infrared thermography technique. Hyalgan
      enhances efficiency of treatment of KJOA.

PMID- 16786649
TI  - [Surgical treatment for compression fractures of the tibia condyles].
AB  - Results are submitted of surgical treatment of 69 patients presenting with
      compression fracture of condyles of the tibia. The elaborated management scheme
      of the above kind of fractures was found to have ensured a positive result in 84
      percent of cases.

PMID- 16786650
TI  - [Problems of surgical aid to HIV-infected and AIDS patients].
AB  - The article focuses on general characterization of HIV-infection, staging of the
      condition, problems of providing surgical aid for AIDS patients and HIV-infected
      subjects. Clinical cases are described of surgical afflictions in this group of
      patients.

PMID- 16786651
TI  - [Effects of low-intensity EHF-radiation on peripheral sections of the nervous
      system].
AB  - A study was made on effects of EHF-radiation on man. The study was conducted in
      40 volunteers who ranged from 20 to 30 years old using the EHF-apparatus "Yav-I"
      (wavelength 7.1 mm, wattage 5 mW/cm2). As a result of 50 min exposure to EHF
      radiation of the area of the GI(II)4 acupuncture point in EEG study a
      rearrangement has been recorded of cortical rhythm patterns characteristic of a
      healthy man, that suggested the development of an unspecific reaction of
      activation such as increase in the tone of the brain cortex. In the investigation
      designed to study indication of EHF EMF, it has been shown that a field with the
      above parameters is recognized by 78 percent of examinees.

PMID- 16786652
TI  - [Biological action of electromagnetic fields of 4 MHz decametric waves].
AB  - Exposure to the amplitude-modulated electromagnetic field, 4 MHZ, 400, 200, and
      100 V/m over two months for 16 hours a day was found out to bring low the
      adaptation potential of a number of bodily physiological systems in animals (non
      linebred rats). Changes in the brain functional activity, cell-bound, and humoral
      immunity were ascertained to be the structural-and-functional basis of
      reorganization of physiological prosesses.

PMID- 16786653
TI  - [Clinical symptomology and character of hormonal shifts in the hypophysial-and
      thyroid system in hypotensive-type autonomic-and-vascular dysfunction in
      adolescents with the history of the perinatal injury of the central nervous
      system].
AB  - As many as 157 juveniles were examined, their age ranging between 11 to 14 years.
      Of these, 69 were healthy subjects who formed the control group, 88 had a history
      of manifestations of hypotensive-type vegetative-and-vascular dysfunction and of
      perinatal pathology. The latter demonstrarted hormonal shifts characterized by
      high functional activity of the thyroid gland, especially so in boys with the
      above pathology under normal values for the thyrotropic function of the pituitary
      gland, which events were noted to be associated with apparent clinical symptoms,
      the most typical of which are cardialgias, headacke, dizziness, undue fatigue,
      changeable moods. The interpretation of the results obtained is given.

PMID- 16786654
TI  - [Prevalence and risk factors for the development of diabetic neuropathy].
AB  - Neuropathology is one of the most commonly encountered complications of diabetes
      mellitus. But we are lacking in exact estimates of the nervous system affliction
      incidence rates in patients with diabetes mellitus in countries of the
      Commonwealth of Independent States. Our objective in this work was to study
      prevalence of diabetic neuropathy and to identify factors predisposing to
      formation of the above complication of diabetes in the Prednistrovye Region of
      Moldova. Overall 250 patients with diabetes mellitus were examined. Relatedness
      has been revealed of the degree of peripheral neuropathy to the level of glycated
      hemoglobin (Hb(AIc)) reflecting the condition of long-term compensation of
      diabetes mellitus, with interrelation having been established of progression of
      the above distress degree of severity, with duration of diabetes mellitus, blood
      plasma reduction in the content of high-density lipoproteins, augmentation of low
      density lipoproteins and triglycerides as well. High incidence of neuropathy
      attests to the need for us to carry out special medical and social measures aimed
      to improve the therapy of patients with diabetes mellitus and to early recognize
      the distress in order that we might lessen the risk for development of chronic
      complications of disease.

PMID- 16786655
TI  - [Transient neonatal hypothyrosis in premature neonates].
AB  - Plasma levels were measured of T4, free T4, T3, TSH in 64 premature neonates and
      in 41 those born at right time during the time-related course of the neonatal
      period. The results secured permit regarding the thyroid hypohormonosis syndrome
      in premature neonates as a consequence of the hypothalamic-hypophyseal-thyroid
      axis deficiency and of immaturity of the thyreostatic receptors as well. On the
      one hand, this promotes hypometabolism and, correspondingly, favours more
      economic utilization of bodily energy resources but on the other hand, such
      adaptation is not infrequently results in its failure and persistent
      thyrodeficiency, especially in very low-birth weight infants, during the whole of
      the neonatal period.

PMID- 16786656
TI  - [Pathogenetic characteristics of trigger mechanisms of preterm birth].
AB  - A study was made into the immune factors capability to induce labour in
      physiologic delivery and in threat of preterm birth. The immune response
      reactivity was proved to be the case immediately before the physiological labour
      and in premature delivery. The studies made showed that a rise in the level of
      lymphocytes and in the subpopulations ratios is a matter of principle in the
      diagnosis and prognosis of the contractile activity of the uterus. Preclinical
      diagnosis of pregnancy suspension permit performing a rational drug correction to
      secure a positive effect on indices for perinatal pathology.

PMID- 16786657
TI  - [Use of inhibitors of the angiotensin-converting enzyme and the beta
      adrenoblocker metoprolol combined in treatment of chronic cardiac insufficiency].
AB  - Clinical-and-hemodynamic effects were studied of a supplementary use of a
      selective beta-adrenoblocker metoprolol in an ongoing therapy of chronic cardiac
      insufficiency (CCI) with inhibitors of the angiotensin-converting enzyme (ACEI)
      and diuretics. It has been found out that long (over 8 weeks) course of therapy
      supplemented with metoprolol results in improvement of the left ventricular
      systolic function and lowering of the functional class. Long-term administration
      of metoprolol enhances tolerance to a graded physical exercise in CCI patients,
      which observation is accompanied by a more economic character of its performance.
      The findings secured validate the expediency of a supplementary use of the beta
      adrenoblocker metoprolol in the routine regimen of the supporting treatment of
      CCI patients involving the use of ACEI plus a diuretic.

PMID- 16786658
TI  - [Effects of wobenzyme on certain indices for the oxidation-antioxidation
      homeostasis and erythrocyte morphofunctional status in elderly and senile
      patients with peptic ulcer].
AB  - Some specifities of mechanisms of the antiradical defence decompensation have
      been ascertained together with changes in morphofunctional properties of red
      cells in gastric and duodenal ulcer concomitant with affection of the
      hepatobiliary system. The need has been demonstrated for supplementing the
      therapeutic complex with the polyenzymic preparation wobenzyme that facilitates
      normalization of the red blood cells' ability to undergo deformation, lowering
      the degree of viscosity of the erythrocytic suspension in the above group of
      patients.

PMID- 16786659
TI  - [Effects of olbetam on lipid reroxidation, the antioxidant system and endogenous
      intoxication in patients with atherosclerosis obliterans of arteries of the lower
      extermities].
AB  - The interrelation was studied of processes of lipid peroxidation (LPO), the
      antioxidant system (AOS) with the level of endogenous intoxication (EI) during
      treatment with olbetam. Before the treatments administered, significantly high
      levels were recordable of LPO, EI against the background of low AOS activity. An
      one-month course of treatment with olbetam was found to be effective in all the
      parameters studied (LPO, AOS, EI). One month after the withdrawal of the drug the
      olbetam action on the AOS activity plasma level of MDA is still observable, with
      the processes of LPO and EI tending to return to normal. The abovestated permits
      recommending olbetam in the treatment of atherosclerosis obliterans of arteries
      of the inferior limbs as a hypolipidemic drug preparation endowed with an
      antioxidant and deintoxicationg activities.

PMID- 16786660
TI  - [Use of deprim in the treatment of depression in an outpatient setting].
AB  - Results are submitted of a clinical trial of deprim of the Lek firm (Slovakia), a
      new drug preparation having an antidepressive effect. Enrolled in a comparative
      randomized investigation were 32 patients with mild to moderately severe
      depressive disorders. Throughout the study being conducted, the time-related
      course of clinical condition was assessed with the aid of the M. Hamilton scale
      assessment of degree of depression. The data secured suggest efficacy of
      employment of the drug deprim in an outpatient psychiatric and general somatic
      practice for treating neurotic depressions of mild to moderately severe degree.

PMID- 16786661
TI  - [Characteristics of the therapy of patients with type II diabetes mellitus and
      metabolic syndrome].
AB  - The article focuses on the action of sugar-lowering drugs of different groups
      (metformin, acarbose, gliquidone, diacamf, food fibre, in patients with type II
      diabetes mellitus presenting with the metabolic syndrome. All studied medicinal
      agents compensated the carbohydrate and lipid metabolism, lowered the body mass,
      delayed the development of atherosclerosis, which facts were found to alleviate
      the manifestations of the metabolic syndrome.

PMID- 16786662
TI  - [Systemic enzymotherapy as a method of prophylaxis of postradiation complications
      in oncological patients].
AB  - Set out in the paper are results of treatment of those patients with carcinoma of
      the lung, uterine cervix, hysterocarcinoma, breast cancer, malignant thymomas,
      malignant non-Hodgkin's lymphomas, and lymphogranulematosis having been
      administered combined, chemoradiation or radiation treatments against the
      background of a complex of accompanying therapy involving systemic enzymotherapy.
      Polyenzymic drugs were found to be capable of improving results of treatment of
      acute radiation reactions and preventing postradiation fibrous changes in the
      lungs, skin, fatty tissue, soft tissue, liver, kidneys. Thus, systemic
      enzymotherapy is capable of improving the quality of life and results of
      treatment of oncological patients.

PMID- 16786663
TI  - [Immunocorrective effect of cycloferon and thymogen in patients with uterine
      cancer].
AB  - Those women diagnosed as having hysterocarcinoma demonstrate even before surgery
      pronounced immunological disturbances tending to progress after surgical
      intervention. The employment of cyclopheronum and thymogenum makes for
      normalization of values for the immune status. Clinically, this is accompanied by
      a more favourable postoperative course.

PMID- 16786664
TI  - [Perspective for using chitin drugs in obstetrical practice].
AB  - The article focuses on structure, physical-and-chemical properties of chitin and
      glucans. An analysis was performed of experimental and clinical results of
      treatment with chitin and glucans. Shown in the paper is a high antibacterial
      activity of the drug mycoton. Its use as a topica or per os results in
      alleviation of signs of local inflammation, earlier transition of the hydration
      phase to the dehydration phase, accelaration of the process of tissue
      regeneration, which fact permits cutting the time of the in-patient's staying in
      hospital by 3.5 to 5.4 days. On the basis of the abovestated the conclusion has
      been reached that mycoton is a chitin-containing drug obtained from higher
      basidial fungi, it can be used as an alternative drug for treating of wound
      infection in the obstetrician's practice.

PMID- 16786665
TI  - [Hypereosinophilic syndrome].
AB  - The article focuses on one of rarely occuring forms of "major eosinophilias"-
      hypereosinophilic syndrome (HES). Based on two observations and data from the
      published literature the clinical presentation of HES is described together with
      affection of different organs, changes in the blood and bone marrow. The article
      has a particular focus on differential diagnosis of HES, symptomatic and clonal
      eosinophilias, importance of cytogenetic investigations. The policy of managing
      patients presenting with the above medical problem is discussed.

PMID- 16786666
TI  - [Morbidity patterns among workers in the porcelain industry].
AB  - Morbidity patterns were studied among female workers engaged in the production of
      porcelain. The above patterns were found to be related to the worker's occupation
      and in a lesser measure to her age. The greatest case rate was among those female
      workers engaged in paint grinding whose work involved the use of organic
      solvents, with the least one recordable in those engaged in burning operations
      exposed to radiant heat. Age-related case rate in the group of women of basic
      occupations was at its highest at ages 30 to 39 years, with the above rate at its
      lowest in the group within 20 to 24 age bracket, acute respiratory viral
      infections coming first.

PMID- 16786668
TI  - [The role of medical risk factors in the development of tuberculosis in the
      military personnel].
AB  - A total of 120 servicemen of the enlisted staff having been taken ill with
      tuberculosis were examined with the purpose of identifying in them medical risk
      factors and assessing the part they play in the development of the illness. 84
      (75%) of those having been fallen ill revealed the following risk factors:
      residual changes after spontaneously cured tuberculosis, abnormalities in the
      immunological reactivity, family and industrial tubcontact, hypersensitivity to
      tuberculin, and other factors. A three-degree scale is submitted for assessment
      of risk for development of tuberculosis in servicemen of the enlisted staff. The
      author considers it inexpediant to call up for military service those young men
      presenting with third degree risk for tuberculosis.

PMID- 16786667
TI  - [Some aspects of damage to the heart in intercurrent exposure to dust and high
      air temperature].
AB  - Albino male rats were exposed to inhalation dusting with rock dust containing 29%
      free silicon dioxide over eight months at air temperature 37-38 degrees C. It has
      been ascertained that combined bodily exposure to dust and high ambient
      temperature promotes the development of prominent hypertrophy and hypoxia of the
      myocardium, activation of the lipid peroxidation processes, resulting in an
      appreciable degree of morphological changes in the cardiac tissue. It is
      suggested that the above changes might be a reflection of development of
      myocardial dystrophy originating in insufficiency of energy supply to the
      cardiomyocytes, that can lead to the development of cardiosclerosis of dystrophic
      genesis. Major disturbances in the myocardial microcirculation, increase in the
      functional load on the heart were found to be those factors favouring the
      development of myocardial dystrophy under the conditions described.

PMID- 16786670
TI  - [Main approaches toward analysis of economic efficiency of medicamentous therapy
      of sexually-transmitted infections].
AB  - The article focuses on those problems related to the assessment of economic
      efficiency of medicamentous therapy of those infections caught by sexual
      intercourse. The chief components are described a reference to which is essential
      in carrying out an analysis of the economic efficiency of the treatments
      administered. The basic factors for optimum ways of performing analysis of the
      treatment from the standpoint of its economic efficiency are determined.

PMID- 16786669
TI  - [Technology of registration of deaths in Ukraine: problems and ways for
      improvement of quality of data about oncological patients].
AB  - Considered in the paper is modern technology of registration of deaths from
      malignant tumors in Ukraine. Ways are submitted for improvement of quality of
      data on life span of oncological patients with the purpose of optimizing the
      organization of the oncological service, securing an objective assessment of
      results of treatment of oncological patients according to mortality indices.

PMID- 16786671
TI  - [Iurii Drohobych--the first Ukranian doctor of medicine].

PMID- 16786672
TI  - Managing growth at ES&T.

PMID- 16786673
TI  - Triclocarban seems to defy wastewater treatment.

PMID- 16786675
TI  - Pesticide mixtures ubiquitous in U.S. streams.

PMID- 16786674
TI  - Fish farms harm local food supply.

PMID- 16786676
TI  - Perchlorate found in produce worldwide.

PMID- 16786677
TI  - NIEHS faces opposition to journal privatization plan.

PMID- 16786678
TI  - EPA's science for you campaign.

PMID- 16786679
TI  - Water desalination takes a step forward.

PMID- 16786680
TI  - Effects of human pharmaceuticals on aquatic life: next steps.

PMID- 16786681
TI  - Biological monitoring of polyfluoroalkyl substances: A review.
AB  - Polyfluoroalkyl substances (PFSs) are used in industrial and commercial products
      and can degrade to persistent perfluorocarboxylates (PFCAs) and perfluoroalkyl
      sulfonates (PFSAs). Temporal trend studies using human, fish, bird, and marine
      mammal samples indicate that exposure to PFSs has increased significantly over
      the past 15-25 years. This review summarizes the biological monitoring of PFCAs,
      PFSAs, and related PFSs in wildlife and humans, compares concentrations and
      contamination profiles among species and locations, evaluatesthe
      bioaccumulation/biomagnification in the environment, discusses possible sources,
      and identifies knowledge gaps. PFSs can reach elevated concentrations in humans
      and wildlife inhabiting industrialized areas of North America, Europe, and Asia
      (2-30,000 ng/ mL or ng/g of wet weight (ww)). PFSs have also been detected in
      organisms from the Arctic and mid-ocean islands (< or = 3000 ng/g ww). In humans,
      PFSAs and PFCAs have been shown to vary among ethnic groups and PFCA/PFSA
      profiles differ from those in wildlife with high proportions of perfluorooctanoic
      acid and perfluorooctane sulfonate. The pattern of contamination in wildlife
      varied among species and locations suggesting multiple emission sources. Food web
      analyses have shown that PFCAs and PFSAs can bioaccumulate and biomagnify in
      marine and freshwater ecosystems. Knowledge gaps with respect to the transport,
      accumulation, biodegradation, temporal/spatial trends and PFS precursors have
      been identified. Continuous monitoring with key sentinel species and
      standardization of analytical methods are recommended.

PMID- 16786682
TI  - Compound class specific 14C analysis of polycyclic aromatic hydrocarbons
      associated with PM10 and PM1.1 aerosols from residential areas of suburban Tokyo.
AB  - Compound class specific radiocarbon analysis (CCSRA) was performed for polycyclic
      aromatic hydrocarbons (PAHs) associated with airborne particulate matter (APM)
      with diameter <10 microm (PM10) and <1.1 microm (PM1.1) collected from a
      residential area of suburban Tokyo, Japan, and seasonal and particle-size
      radiocarbon variations were investigated. Source diagnostic isomer pair ratios
      indicated mixed contributions from petroleum combustion and from biomass and coal
      combustion to the PAHs in APM. The delta14C- PAHs in APM, ranging from -787 to 
      514 per thousand, indicated dominance of fossil fuel combustion. The delta14C of
      5-6 rings (HMW) PAHs were higher than the 3-4 rings (LMW) species in both PM10
      and PM1.1 samples. The delta14C of HMW-PAHs indicated greater biomass-burning
      contributions in summer than in winter and no apparent particle-size variation.
      Conversely, the delta14C of LMW species showed a greater contribution from fossil
      sources in summer and in larger particles (PM10). This finding could be
      tentatively attributed to the recondensation of fossil-PAHs vaporized from
      petroleum sources. A 14C isotopic mass balance approach estimated that biomass
      burning contributes 17-45% of the PAH burden in suburban Tokyo, and that the
      increase in the biomass-PAH accounts for approximately 27% and 22% of winter-time
      elevation of LMW- and HMW-PAHs, respectively. These are far exceeding what is
      expected from the emission statistics for CO2 and combusted materials in Japan
      and emphasizing the importance of biomass-burning as a source of PAHs; which, in
      turn, demonstrates the utility and the significance of field-based source
      assessment by using CCSRA for an effective regulation of atmospheric pollution by
      PAHs.

PMID- 16786683
TI  - Sorption of phthalate esters and PCBs in a marine ecosystem.
AB  - Dialkyl phthalate esters (DPEs) are widely used industrial chemicals with octanol
      seawater partition coefficients ranging between 10(1.80) for dimethyl phthalate
      to 10(10.0) for diiso-decyl phthalate, indicating a propensity to sorb strongly
      to particulate matter in aquatic environments. Sorption plays a key role in
      controlling the long-term fate of DPEs in aquatic systems and exposure to
      organisms in aquatic food-webs. However, field observations of the sorption of
      many commercial DPEs do not exist. To characterize the sorptive nature of DPEs in
      a real-world aquatic ecosystem, we measured concentrations of DPEs congeners,
      commercial DPE mixtures, and 10 polychlorinated biphenyls (PCBs) in water,
      suspended sediments, and bottom sediments of a marine inlet. Sorption
      coefficients of spiked and native DPEs and PCBs between suspended sediments and
      water indicate that the apparent sorptive nature of DPEs and PCBs is
      substantially greater than expected from K(ow)-based sorption models. Particulate
      and dissolved organic matter showed similar (i.e., not statistically different)
      sorption affinities for native analytes. The apparent fraction of the total
      aqueous concentration of DPEs that is freely dissolved and absorbable via the
      respiratory tract of aquatic organisms varied from virtually 100% for DMP to
      0.0003% for C10. The observed decline in concentration of most DPEs between
      suspended and bottom sediments, compared to an increase in the concentration of
      high Kow PCBs, suggests that the rate of desorption and degradation of DPEs
      exceeds that of organic carbon mineralization and contributes to the previously
      observed lack of biomagnification of DPEs in the aquatic food-web of this system.

PMID- 16786684
TI  - Ecosystemic effects of salmon farming increase mercury contamination in wild
      fish.
AB  - Net-pen salmon aquaculture has well-known effects on coastal ecosystems: farm
      waste increases sediment organic content and the incidence of sediment anoxia,
      supports increased production of deposit-feeding invertebrates, and attracts
      higher densities of demersal fish and other mobile carnivores. These impacts are
      widely considered to be localized and transitory, and are commonly managed by
      imposing a period of fallowing between cycles of production. The implications of
      these ecosystemic effects for contaminant cycling, however, have not previously
      been considered. We found elevated levels of mercury in demersal rockfishes near
      salmon farms in coastal British Columbia, Canada, attributable to a combination
      of higher rockfish trophic position and higher mercury levels in prey near farms.
      Mercury concentrations in long-lived species such as rockfishes change over a
      longer time scale than cycles of production and fallowing, and thus at least some
      important effects of fish farms may not be considered transitory.

PMID- 16786685
TI  - Landscape control of stream water aluminum in a boreal catchment during spring
      flood.
AB  - Inorganic aluminum (Al) concentrations are critical for defining the biological
      effects of acidification. The landscape's role in controlling the spatial
      variability of Al and its speciation has received only limited attention. We
      analyzed the speciation of stream Al at 14 sites within a 68 km2 boreal catchment
      during spring snowmelt, a period of episodic acidity. Three factors that
      influenced Al at these sites were landscape type (specifically the proportion of
      wetland areas), stream pH, and dissolved organic carbon (DOC). Forested catchment
      sites underlain by mineral soils had higher total Al concentrations and greater
      inorganic Al proportions than catchments with larger wetland areas, despite
      significantly higher pH. We suggest that this difference results from source
      limitation of Al in the peat wetlands. The control of Al solubilitywas dominated
      by organic complexes, with the organic carrying capacity exceeding Al in the
      majority of samples. When assessing the inorganic phase, only four percent of the
      samples were oversaturated with regards to commonly forming secondary Al
      minerals, with no samples showing supersaturation higher than 10 times with
      respect to any given solid phase. Inorganic Al rarely exceeded biological
      thresholds, except for short periods during peak flow in forested areas, despite
      two-thirds of the streams having minimum pH values below 4.9. Streams with a high
      percentage of wetland area were associated with lower Al:DOC ratios. The Al:DOC
      ratios were quite stable in each stream before, during, and after snowmelt, with
      the exception of isolated spikes in the Al:DOC ratio associated with particulate
      Al at a downstream site during high flow.

PMID- 16786686
TI  - Experimental evidence for a lack of thermodynamic control on hydrogen
      concentrations during anaerobic degradation of chlorinated ethenes.
AB  - Hydrogen (H2) concentrations during reductive dechlorination of cis
      dichloroethene (cDCE) and vinyl chloride (VC) were investigated with respectto
      the influence of parameters entering the Gibbs free energy expression of the
      reactions. A series of laboratory experiments was conducted employing a mixed,
      Dehalococcoides-containing enrichment culture capable of complete dechlorination
      of chlorinated ethenes. The objective was to investigate whether a constant
      energy gain controls H2 levels in dechlorinating systems, thereby evaluating the
      applicability of the partial equilibrium approach to microbial dechlorination at
      contaminated sites. Variations in the temperature between 10 and 30 degrees C did
      not affect the H2 concentration in a fashion that suggested thermodynamic control
      through a constant energy gain. In another set of experiments, H2 levels at
      constant ionic strength were independent of the chloride concentration between 10
      and 110 mmol chloride per liter. These findings demonstrate that the partial
      equilibrium approach is not directly applicable to the interpretation of
      reductive degradation of chlorinated ethenes. We also present recalculated
      thermodynamic properties of aqueous chlorinated ethene species that allow for
      calculation of in-situ Gibbs free energy of dechlorination reactions at different
      temperatures.

PMID- 16786687
TI  - Plutonium oxidation and subsequent reduction by Mn(IV) minerals in Yucca Mountain
      tuff.
AB  - Plutonium oxidation state distribution on Yucca Mountain tuff and synthetic
      pyrolusite (beta-MnO2) suspensions was measured using synchrotron X-ray micro
      spectroscopy and microimaging techniques as well as
      ultrafiltration/solventextraction techniques. Plutonium sorbed to the tuff was
      preferentially associated with manganese oxides. For both Yucca Mountain tuff and
      synthetic pyrolusite, Pu(IV) or Pu(V) was initially oxidized to more mobile
      Pu(V/VI), but over time, the less mobile Pu(IV) became the predominant oxidation
      state of the sorbed Pu. The observed stability of Pu(IV) on oxidizing surfaces
      (e.g., pyrolusite), is proposed to be due to the formation of a stable hydrolyzed
      Pu(IV) surface species. These findings have important implications in estimating
      the risk associated with the geological burial of radiological waste in areas
      containing Mn-bearing minerals, such as at the Yucca Mountain or the Hanford
      Sites, because plutonium will be predominantly in a much less mobile oxidation
      state (i.e., Pu(IV)) than previously suggested (i.e., Pu(V/VI).

PMID- 16786688
TI  - Aqueous oxidation of substituted dihydroxybenzenes by substituted benzoquinones.
AB  - Strict anaerobic techniques, HPLC, and spectrophotometry are employed to explore
      rates of reaction between a series of substituted benzoquinone oxidants and
      substituted dihydroxybenzene reductants, which represent important redox-active
      moieties within natural organic matter (NOM). Benzoquinones and dihydroxybenzenes
      that lack electron-withdrawing substituents exhibit reversible reactions within
      the acidic range of natural waters. Initial rates for reversible reactions are
      proportional to [H+]-1, attributable to the greater reactivity of monoprotonated
      versus diprotonated dihydroxybenzene molecules. Reversible reactions are
      generally faster for pairs having higher thermodynamic driving force.
      Concentrations in reversible reactions eventually reach plateau values, which
      coincide with expected values calculated using standard reduction potentials. If
      a reactant benzoquinone possesses an electron-withdrawing substituent, reaction
      progress falls short of expected values. If a product benzoquinone possesses an
      electron-withdrawing substituent, reaction progress extends beyond what is
      thermodynamically predicted. Electron-withdrawing substituents raise the
      susceptibility of benzoquinones to side reactions such as the Michael addition
      reaction.

PMID- 16786689
TI  - Sorption of Am(III) onto 6-line-ferrihydrite and its alteration products:
      investigations by EXAFS.
AB  - For the long-term performance assessment of nuclear waste repositories, knowledge
      about the interactions of actinide ions with mineral surfaces such as iron oxides
      is imperative. The mobility of released radionuclides is strongly dependent on
      the sorption/desorption processes at these surfaces and on their incorporation
      into the mineral structure. In this study the interaction of Am(III) with 6-line
      ferrihydrite (6LFh) was investigated by EXAFS spectroscopy. At low pH values (pH
      5.5), as well at higher pH values (pH 8.0), Am(III) sorbs as a bidentate corner
      sharing species onto the surface. Investigations of the interaction of Am(III)
      with Fh coated silica colloids prove the sorption onto the iron coating and not
      onto the silica substrate. Hence, the presence of Fh, even as sediment coating,
      is the dominant sorption surface. Upon heating, Fh is transformed into goethite
      and hematite as shown by TEM and IR measurements. The results of the fit to the
      EXAFS data indicate the release of sorbed Am(III) at pH 5.5 during the
      transformation and likely a partial incorporation of Am into the Fh
      transformation products at pH 8.0.

PMID- 16786690
TI  - Reoxidation behavior of technetium, iron, and sulfur in estuarine sediments.
AB  - Technetium is a redox active radionuclide, which is present as a contaminant at a
      number of sites where nuclear fuel cycle operations have been carried out. Recent
      studies suggest that Tc(VII), which is soluble under oxic conditions, will be
      retained in sediments as Fe(III)-reducing conditions develop, due to reductive
      scavenging as hydrous TcO2. However, the behavior of technetium during subsequent
      reoxidation of sediments remains poorly characterized. Here, we describe a
      microcosm-based approach to investigate the reoxidation behavior of reduced,
      technetium-contaminated sediments. In reoxidation experiments, the behavior of Tc
      was strongly dependent on the nature of the oxidant. With air, reoxidation of
      Fe(II) and, in sulfate-reducing sediments, sulfide occurred accompanied by
      approximately 50% remobilization of Tc to solution as TcO4-. With nitrate,
      reoxidation of Fe(II) and, in sulfate-reducing sediments, sulfide only occurred
      in microbially active experiments where Fe(II) and sulfide oxidation coupled to
      nitrate reduction was occurring. Here, Tc was recalcitrant to remobilization with
      <10% Tc remobilized to solution even when extensive Fe(II) and sulfide
      reoxidation had occurred. X-ray absorption spectroscopy on reoxidized sediments
      suggested that 15-50% of Tc bound to sediments was present as Tc(VII). Overall,
      these results suggest that Tc reoxidation behavior is not directly coupled to Fe
      or S oxidation and that the extent of Tc remobilization is dependent on the
      nature of the oxidant.

PMID- 16786691
TI  - Investigation of alpha-pinene + ozone secondary organic aerosol formation at low
      total aerosol mass.
AB  - We present a method for measuring secondary organic aerosol (SOA) production at
      low total organic mass concentration (COA) using proton-transfer reaction mass
      spectrometry (PTR-MS). PTR-MS provides high time resolution measurements of gas
      phase organic species and, coupled with particle measurements, allows for the
      determination of aerosol yield in real time. This approach facilitates the
      measurement of aerosol production at low COA; in fact aerosol mass fractions can
      be measured during alpha-pinene consumption as opposed to only at the completion
      of gas-phase chemistry. The high time resolution data are consistent with both
      the partitioning theory of Pankow (Atmos. Environ. 1994, 28,185 and 189) and the
      previous experimental measurements. Experiments including the effect of UV
      illumination and NOx reveal additional features of alpha-pinene + ozone product
      photochemistry and volatility. The high time resolution data also elucidate
      aerosol production from alpha-pinene ozonolysis at COA < 10 microg m(-3) and show
      that extrapolations of current partitioning models to conditions of low COA
      significantly underestimate SOA production under dark, low-NOx conditions.
      However, extrapolations of current models overestimate SOA production under
      illuminated, higher-NOx conditions typical of polluted regional air masses.

PMID- 16786692
TI  - Thermodynamic constraints on the oxidation of biogenic UO2 by Fe(III)
      (Hydr)oxides.
AB  - Uranium mobility in the environment is partially controlled by its oxidation
      state, where it exists as either U(VI) or U(IV). In aerobic environments, uranium
      is generally found in the hexavalent form, is quite soluble, and readily forms
      complexes with carbonate and calcium. Under anaerobic conditions, common metal
      respiring bacteria can reduce soluble U(VI) species to sparingly soluble UO2
      (uraninite); stimulation of these bacteria, in fact, is being explored as an in
      situ uranium remediation technique. However, the stability of biologically
      precipitated uraninite within soils and sediments is not well characterized. Here
      we demonstrate that uraninite oxidation by Fe(III) (hydr)oxides is
      thermodynamically favorable under limited geochemical conditions. Our analysis
      reveals that goethite and hematite have a limited capacity to oxidize
      UO2(biogenic) while ferrihydrite can lead to UO2(biogenic) oxidation. The extent
      of UO2(biogenic) oxidation by ferrihydrite increases with increasing bicarbonate
      and calcium concentration, but decreases with elevated Fe(II)(aq) and U(VI)(aq)
      concentrations. Thus, our results demonstrate that the oxidation of UO2(biogenic)
      by Fe(III) (hydr)oxides may transpire under mildly reducing conditions when
      ferrihydrite is present.

PMID- 16786693
TI  - Geochemical modeling of leaching from MSWI air-pollution-control residues.
AB  - This paper provides an improved understanding of the leaching behavior of waste
      incineration air-pollution-control (APC) residues in a long-term perspective.
      Leaching was investigated by a series of batch experiments reflecting leaching
      conditions after initial washout of highly soluble salts from residues. Leaching
      experiments were performed at a range of pH-values using carbonated and
      noncarbonated versions of two APC residues. The leaching data were evaluated by
      geochemical speciation modeling and discussed with respect to possible solubility
      control. The leaching of major elements as well as trace elements was generally
      found to be strongly dependent on pH. As leaching characterization was performed
      in the absence of high salt levels, the presented results represent long-term
      leaching after initial washout from a disposal site, that is, liquid-to-solid
      ratios above 1-2 L/kg. The leaching of Al, Ba, Ca, Cr, Pb, S, Si, V, and Zn was
      found influenced by solubility control from A12O3, Al(OH)3, Ba(S,Cr)04 solid
      solutions, BaSO4, Ca6Al2(SO4)3(OH)12 x 26H2O, CaAl2Si4O12 x 2H2O, Ca(OH)2,
      CaSiO3, CaSO4 x 2H2O, CaZn2(OH)6 x 2H2O, KAlSi2O6, PbCO3, PbCrO4, Pb2O3, Pb2V2O7,
      Pb3(VO4)2, ZnO, Zn2SiO4, and ZnSiO3. The presented dataset and modeling results
      form a thorough contribution to the assessment of long-term leaching behavior of
      APC residues under a wide range of conditions.

PMID- 16786694
TI  - Regressing gas/particle partitioning data for polycyclic aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) were measured in the rural atmosphere of
      Southern Ontario, Canada from October 2001 to November 2002. Sixty seven pairs of
      gaseous and particle-bound concentrations of PAHs were determined concurrently in
      a forest and a clearing. The gas/particle partitioning behavior of the PAHs was
      investigated by fitting the original Junge-Pankow equation to the fraction in the
      particle phase phi for each set of measured data, either allowing the slope m to
      deviate from -1 (two-parameter model) or not (one-parameter model). This fitting
      procedure was judged more robust than linear logarithmic regressions involving
      the gas/particle partition coefficient, because the latter is sensitive to the
      applied blank correction, tends to ignore a significant amount of analytical
      information, and gives undue weight to more uncertain data points. The
      experimental data fit was good for both nonlinear models, and discrepancies
      between experimental data and models and between models are mostly related to
      sampling/experimental artifacts. In particular, samples taken close to the
      freezing point appear to suffer from blow-off artifacts. Applying slopes m
      different from -1 appears only justified if it can be assured that a second
      parameter indeed provides a better fit and that this better fit is not due to
      experimental, analytical, or statistical artifacts. The magnitude of the
      differences in the model fitting parameters between sampling events is consistent
      with the reported variability in the nature and concentration of atmospheric
      particles. Statistical tests on the regression results indicate that the
      gas/particle partitioning was not significantly different between the forest and
      the clearing.

PMID- 16786695
TI  - Modeling the impact of a benzene source zone on the transport behavior of PAHs in
      groundwater.
AB  - Aquifers at industrial sites are commonly characterized by a multitude of
      contaminant source zones. Conceivably, dissolved contaminants originating from an
      up-gradient residual nonaqueous phase liquid (NAPL) source zone may be
      transported along the groundwater flow path into another residual NAPL source
      zone down-gradient. However, if and how contaminants from different zones may
      affect one another with regard to dissolution and transport has thus far been
      unknown. To identify and understand such potential interactions, the numerical
      model BIONAPL3D was applied to simulate the behavior of six dissolved polycyclic
      aromatic hydrocarbons (PAHs), stemming simultaneously from an up-gradient NAPL
      source zone, when they encounter a down-gradient NAPL source zone. The down
      gradient NAPL source zone was assumed to be a residual benzene phase with a
      saturation of 10%. When the dissolved PAHs entered the benzene source zone, the
      aqueous PAH concentrations declined significantly due to their partitioning into
      the residual benzene phase. As benzene rapidly dissolved intothe aqueous
      phase,the PAHswere resolubilized with negligible impact due to benzene co
      solvency. The degree of resolubilization was much smaller than the initial loss
      due to partitioning into the benzene phase. Thus, the PAHs formed a new residual
      NAPL phase that, over time, replaced the original benzene source zone. The new
      NAPL phase continued to grow even after all of the benzene was dissolved. Our
      modeling approach is the first theoretical demonstration of a significant
      interaction of contaminants emanating from multiple source zones. It should be
      regarded as a starting point to consider source zone interactions at polluted
      field sites.

PMID- 16786696
TI  - The partition behavior of fluorotelomer alcohols and olefins.
AB  - In this paper we present a number of equilibrium partition constants for
      fluorotelomer alcohols and olefins among them data for air/water and octanol/air
      partitioning. These data are typically required for environmental fate modeling.
      Our data deviate substantially from those in the literature. A comprehensive
      check for consistency and plausibility strongly suggests that the data published
      here are correct. As a consequence the fluorotelomer alcohols will sorb much more
      to organic phases and have a smaller tendency to remain in the water phase than
      expected based on previous data. The presented partition data also allow us to
      derive descriptors for the various kinds of specific (e.g., H-bonds) and
      nonspecific (e.g., van der Waals) intermolecular interactions thatthe compounds
      can undergo. These descriptors can be used in polyparameter linear free energy
      relationships (pp-LFER) in orderto predict a large variety of other partition
      coefficients (e.g., air/solvent, solvent/ water) as well as the temperature
      dependence of their air/ water partitioning. The experimental and theoretical
      approach that we present here can serve as a general example for what needs to be
      done in order to ensure high quality physicochemical data for organic pollutants.

PMID- 16786697
TI  - Modeling the probability of arsenic in groundwater in New England as a tool for
      exposure assessment.
AB  - We developed a process-based model to predict the probability of arsenic
      exceeding 5 microg/L in drinking water wells in New England bedrock aquifers. The
      model is being used for exposure assessment in an epidemiologic study of bladder
      cancer. One important study hypothesis that may explain increased bladder cancer
      risk is elevated concentrations of inorganic arsenic in drinking water. In
      eastern New England, 20-30% of private wells exceed the arsenic drinking water
      standard of 10 micrograms per liter. Our predictive model significantly improves
      the understanding of factors associated with arsenic contamination in New
      England. Specific rock types, high arsenic concentrations in stream sediments,
      geochemical factors related to areas of Pleistocene marine inundation and
      proximity to intrusive granitic plutons, and hydrologic and landscape variables
      relating to groundwater residence time increase the probability of arsenic
      occurrence in groundwater. Previous studies suggest that arsenic in bedrock
      groundwater may be partly from past arsenical pesticide use. Variables
      representing historic agricultural inputs do not improve the model, indicating
      that this source does not significantly contribute to current arsenic
      concentrations. Due to the complexity of the fractured bedrock aquifers in the
      region, well depth and related variables also are not significant predictors.

PMID- 16786699
TI  - Measuring hydrophobic micropore volumes in geosorbents from trichloroethylene
      desorption data.
AB  - Hydrophobic micropores can play a significant role in controlling the long-term
      release of organic contaminants from geosorbents. We describe a technique for
      quantifying the total and the hydrophobic mineral micropore volumes based on the
      mass of trichloroethylene (TCE) sorbed in the slow-releasing pores under dry and
      wet conditions, respectively. Micropore desorption models were used to
      differentiate the fast- and slow-desorbing fractions in desorption profiles. The
      micropore environment in which organic molecules were sorbed in the presence of
      water was probed by studying the transformation of a water-reactive compound (2,2
      dichloropropane or 2,2-DCP). For sediment from an alluvial aquifer, the total and
      hydrophobic micropore volumes estimated using this technique were 4.65 microL/g
      and 0.027 microL/g (0.58% of total), respectively. In microporous silica gel A, a
      hydrophobic micropore volume of 0.038 microL/g (0.035% of reported total) was
      measured. The dehydrohalogenation rate of 2,2-DCP sorbed in hydrophobic
      micropores of the sediment was slower than that reported in bulk water,
      indicating an environment of low water activity. The results suggest that
      hydrolyzable organic contaminants sorbed in hydrophobic micropores react slower
      than in bulk water, consistent with the reported persistence of reactive
      contaminants in natural soils.

PMID- 16786700
TI  - New method for testing phototoxicity of polycyclic aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs), widespread environmental pollutants,
      were recently reported to show photomutagenesis. As contaminants in the
      environment are usually exposed to sunlight, a way to evaluate the phototoxic
      characteristics of pollutants is required. We have previously found that
      phosphorylation of histone H2AX (gamma-H2AX), which accompanied the induction of
      DNA double strand breaks (DSBs), was significantly induced by low concentrations
      of benzo[a]pyrene (10(-9)-10(-7) M) and UVA (0.6 J/cm2) in CHO-K1 cells. Higher
      concentrations have been required for the detection of DSBs. The aim of the
      present study is to investigate the applicability of gamma-H2AX in a new
      phototoxicity assay of PAHs. The human keratinocytes, HaCaT, were treated with
      four model PAHs (naphthalene, phenanthrene, pyrene, and benzo[a]pyrene, 10(-11)
      10(-7) M) and/or UVA (5 J/cm2), and the induction of gamma-H2AX was assessed.
      Furthermore, DSBs were directly detected using a biased sinusoidal field gel
      electrophoresis, and the cell viability was examined as a general assay of
      phototoxicity. The induction of gamma-H2AX was detected in the presence of all
      the PAHs except naphthalene at concentrations of 10(-9)-10(-7) M, whereas neither
      DSBs nor cell death could be detected at those concentrations, and higher
      concentrations were required for the detection. Naphthalene showed no
      phototoxicity in any of the three different assays. These findings suggest that
      histone H2AX is a potential moleculartargetfor detecting the phototoxicity of
      PAHs more sensitively than the detection of cell viability and DSBs.

PMID- 16786698
TI  - The global atmospheric environment for the next generation.
AB  - Air quality, ecosystem exposure to nitrogen deposition, and climate change are
      intimately coupled problems: we assess changes in the global atmospheric
      environment between 2000 and 2030 using 26 state-of-the-art global atmospheric
      chemistry models and three different emissions scenarios. The first (CLE)
      scenario reflects implementation of current air quality legislation around the
      world, while the second (MFR) represents a more optimistic case in which all
      currently feasible technologies are applied to achieve maximum emission
      reductions. We contrast these scenarios with the more pessimistic IPCC SRES A2
      scenario. Ensemble simulations for the year 2000 are consistent among models and
      show a reasonable agreement with surface ozone, wet deposition, and NO2 satellite
      observations. Large parts of the world are currently exposed to high ozone
      concentrations and high deposition of nitrogen to ecosystems. By 2030, global
      surface ozone is calculated to increase globally by 1.5 +/- 1.2 ppb (CLE) and 4.3
      +/- 2.2 ppb (A2), using the ensemble mean model results and associated +/-1 sigma
      standard deviations. Only the progressive MFR scenario will reduce ozone, by -2.3
      +/- 1.1 ppb. Climate change is expected to modify surface ozone by -0.8 +/- 0.6
      ppb, with larger decreases over sea than over land. Radiative forcing by ozone
      increases by 63 +/- 15 and 155 +/- 37 mW m(-2) for CLE and A2, respectively, and
      decreases by -45 +/- 15 mW m(-2) for MFR. We compute that at present 10.1% of the
      global natural terrestrial ecosystems are exposed to nitrogen deposition above a
      critical load of 1 g N m(-2) yr(-1). These percentages increase by 2030 to 15.8%
      (CLE), 10.5% (MFR), and 25% (A2). This study shows the importance of enforcing
      current worldwide air quality legislation and the major benefits of going
      further. Nonattainment of these air quality policy objectives, such as expressed
      by the SRES-A2 scenario, would further degrade the global atmospheric
      environment.

PMID- 16786702
TI  - Mass transfer within electrostatic precipitators: in-flight adsorption of mercury
      by charged suspended particulates.
AB  - Electrostatic precipitation is the dominant method of particulate control used
      for coal combustion, and varying degrees of mercury capture and transformation
      have been reported across ESPs. Nevertheless, the fate of gas-phase mercury
      within an ESP remains poorly understood. The present analysis focuses on the gas
      particle mass transfer that occurs within a charged aerosol in an ESP. As a
      necessary step in gas-phase mercury adsorption or transformation, gas-particle
      mass transfer-particularly in configurations other than fixed beds-has received
      far less attention than studies of adsorption kinetics. Our previous analysis
      showed that only a small fraction of gas-phase mercury entering an ESP is
      likelyto be adsorbed by collected particulate matter on the plate electrodes. The
      present simplified analysis provides insight into gas-particle mass transfer
      within an ESP under two limiting conditions: laminar and turbulent fluid flows.
      The analysis reveals that during the process of particulate collection, gas
      particle mass transfer can be quite high, easily exceeding the mass transfer to
      ESP plate electrodes in most cases. Decreasing particle size, increasing particle
      mass loading, and increasing temperature all result in increased gas-particle
      mass transfer. The analysis predicts significantly greater gas-particle mass
      transfer in the laminar limitthan in the turbulent limit; however, the
      differences become negligible under conditions where other factors, such as total
      mass of suspended particulates, are the controlling mass transfer parameters.
      Results are compared to selected pilot- and full-scale sorbent injection data.

PMID- 16786701
TI  - Occurrence and removal of chloro-s-triazines in water treatment plants.
AB  - Atrazine, simazine, and propazine and their major chlorinated degradates
      (deethylatrazine, deisopropylatrazine, and didealkylatrazine) are considered as a
      group to be endocrine-disrupting chemicals by the U.S. Environmental Protection
      Agency. On this basis, regulatory action levels are currently under consideration
      for the total chloro-s-triazine (TCT) levels in drinking waters. To assess the
      concentrations of each of these species in drinking water and their treatability
      in conventional water treatment, a comprehensive, full-scale studywas conducted
      that included frequent monitoring at 33 and 47 water utilities during 2003 and
      2004, respectively. Approximately 900 paired raw and treated water samples were
      analyzed using a gas chromatography/mass spectrometry method with
      preconcentration using a mixed-mode, solid-phase extraction that allowed
      quantitation of each species including didealkylatrazine. The results showed that
      atrazine concentrations were generally well within the 3 microg/L maximum
      contaminant level (MCL) and that simazine and propazine concentrations were
      generally negligible. Ninety-fifth-percentile values for the ratio of
      TCT/atrazine were 4.8 and 4.7, respectively. Effectiveness of conventional
      treatment technologies, including carbon, was observed to vary significantly.
      Concerns that didealkyatrazine concentrations may be high and significantly
      elevate the TCT appear to be unfounded. In general, the results suggest that
      potential treatment requirements for TCT are not likely to be any more difficult
      for utilities to meet than the current requirements for atrazine.

PMID- 16786703
TI  - Biological enhancement of tetrachloroethene dissolution and associated microbial
      community changes.
AB  - A bench-scale study was performed to evaluate the enhancement of
      tetrachloroethene (PCE) dissolution from a dense nonaqueous phase liquid (DNAPL)
      source zone due to reductive dechlorination. The study was conducted in a pair of
      two-dimensional bench-scale aquifer systems using soil and groundwater from Dover
      Air Force Base, DE. After establishment of PCE source zones in each aquifer
      system, one was biostimulated (addition of electron donor) while the other was
      biostimulated and then bioaugmented with the KB1 dechlorinating culture.
      Biostimulation resulted in the growth of iron-reducing bacteria (Geobacter) in
      both systems as a result of the high iron content of the Dover soil. After
      prolonged electron donor addition methanogenesis dominated, but no dechlorination
      was observed. Following bioaugmentation of one system, dechlorination to ethene
      was achieved, coincident with growth of introduced Dehalococcoides and other
      microbes in the vicinity and downgradient of the PCE DNAPL (detected using DGGE
      and qPCR). Dechlorination was not detected in the nonbioaugmented system over the
      course of the study, indicating that the native microbial community, although
      containing a member of the Dehalococcoides group, was not able to dechlorinate
      PCE. Over 890 days, 65% of the initial emplaced PCE was removed in the
      bioaugmented, dechlorinating system, in comparison to 39% removal by dissolution
      from the nondechlorinating system. The maximum total ethenes concentration (3 mM)
      in the bioaugmented system occurred approximately 100 days after bioaugmentation,
      indicating that there was at least a 3-fold enhancement of PCE dissolution atthis
      time. Removal rates decreased substantially beyond this time, particularly during
      the last 200 days of the study, when the maximum concentrations of total ethenes
      were only about 0.5 mM. However, PCE removal rates in the dechlorinating system
      remained more than twice the removal rates of the nondechlorinating system. The
      reductions in removal rates over time are attributed to both a shrinking DNAPL
      source area, and reduced flow through the DNAPL source area due to bioclogging
      and pore blockage from methane gas generation.

PMID- 16786704
TI  - Partitioning, persistence, and accumulation in digested sludge of the topical
      antiseptic triclocarban during wastewater treatment.
AB  - The topical antiseptic agent triclocarban (TCC) is a common additive in many
      antimicrobial household consumables, including soaps and other personal care
      products. Long-term usage of the mass-produced compound and a lack of
      understanding of its fate during sewage treatment motivated the present mass
      balance analysis conducted at a typical U.S. activated sludge wastewater
      treatment plant featuring a design capacity of 680 million liters per day. Using
      automated samplers and grab sampling, the mass of TCC contained in influent,
      effluent, and digested sludge was monitored by isotope dilution liquid
      chromatography (tandem) mass spectrometry. The average mass of TCC (mean +/-
      standard deviation) entering and exiting the plant in influent (6.1 +/- 2.0
      microg/L) and effluent (0.17 +/- 0.03 microg/ L) was 3737 +/- 694 and 127 +/- 6
      g/d, respectively, indicating an aqueous-phase removal efficiency of 97 +/- 1%.
      Tertiary treatment by chlorination and sand filtration provided no detectable
      benefit to the overall removal. Due to strong sorption of TCC to wastewater
      particulate matter (78 +/- 11% sorbed), the majority of the TCC mass was
      sequestered into sludge in the primary and secondary clarifiers of the plant.
      Anaerobic digestion for 19 days did not promote TCC transformation, resulting in
      an accumulation of the antiseptic compound in dewatered, digested municipal
      sludge to levels of 51 +/- 15 mg/kg dry weight (2815 +/- 917 g/d). In addition to
      the biocide mass passing through the plant contained in the effluent (3 +/- 1%),
      76 +/- 30% of the TCC input entering the plant underwent no net transformation
      and instead partitioned into and accumulated in municipal sludge. Based on the
      rate of beneficial reuse of sludge produced by this facility (95%), which exceeds
      the national average (63%), study results suggest that approximately three
      quarters of the mass of TCC disposed of by consumers in the sewershed of the
      plant ultimately is released into the environment by application of municipal
      sludge (biosolids) on land used in part for agriculture.

PMID- 16786705
TI  - Cathepsin B and glutathione peroxidase show differing transcriptional responses
      in the grass shrimp, Palaemonetes pugio following exposure to three xenobiotics.
AB  - The common molecular biology techniques, suppressive-subtractive hybridization
      (SSH) and semi-quantitative real-time PCR (SQRT-PCR), were used to identify
      differentially expressed genes in the grass shrimp, Palaemonetes pugio following
      exposure to three different xenobiotics. Lab-acclimated adult male grass shrimp
      were exposed to empirically derived 96-hr male-specific LC50 concentrations of
      fipronil (FP, a phenylpyrazole GABA disrupting pesticide), endosulfan (ES, a
      cyclodiene GABA disrupting pesticide), or cadmium (Cd), as well as a control
      (CC). An SSH gene expression library was constructed from surviving shrimp from
      the fipronil and control exposures. Clones obtained by SSH were identified by
      searching against the NCBI website. A total of 42 genes were identified that were
      up-regulated by FP exposure, and 47 that were down-regulated. A subset of the
      affected genes was tested with SQRT-PCR to verify responsiveness to fipronil, as
      well as to endosulfan and cadmium. Two genes showed strong and significant
      responses to the exposures: glutathione peroxidase was significantly up-regulated
      by all three exposures, while Cathepsin B was strongly responsive to the two
      pesticides, but not to cadmium.

PMID- 16786707
TI  - Comment on "fate of rising CO2 droplets in seawater".

PMID- 16786706
TI  - Absolute transcript expression signatures of Cyp and Gst genes in Mus spretus to
      detect environmental contamination.
AB  - We evaluated whether quantitation of mRNA molecules of key genes is a reliable
      biomonitoring end-point. We examined the Mus spretus expression levels of 19
      transcripts encoding different cytochrome-P450s and glutathione transferases.
      Mice dwelling at the Donana Biological Reserve were compared to those from an
      industrial settlement (PS). Metal biomonitoring indicated that PS animals
      sustained a heavier pollutant burden than those from the reference site.
      Transcript quantitations showed the following: (i) gender-related differences in
      the expression of most Cyp and Gst genes; (ii) one PS female displaying much
      smaller/larger transcript amounts than the remaining females; (iii) the
      concomitant up-regulation of Cyp1a2, Cyp2a5, Cyp2e1, Cyp4a10, Gsta1, Gsta2,
      Gstm1, and Gstm2 mRNAs in liver of PS males; and (iv) outstanding qualitative and
      quantitative differences between the hepatic expression signature of PS males and
      that promoted by paraquat. We conclude that (i) absolute amounts of transcripts
      encoding biotransformation enzymes are more potent biomarkers in males than in
      females, and in liver than in kidney; (ii) individual quantitations prevent
      biased interpretations by specimens with abnormal expression levels; and
      (iii)transcript expression signature of PS males is consistent with exposure to a
      complex profile of organic pollutants, other than oxidative stressors.

PMID- 16786708
TI  - Comment on "parking lot sealcoat: an unrecognized source of urban polycyclic
      aromatic hydrocarbons".

PMID- 16786709
TI  - [Epilepsy and male sexual dysfunction: etiology, diagnosis and therapy].
AB  - While 10% of healthy men had sexual dysfunctions, male epilepsy patients
      experience sexual problems in 40-70%. The cause of sexual dysfunction in epilepsy
      is multifactorial, but there are three main factors: the epilepsy itself,
      antiepileptic treatment and psychiatric/psychic problems. Antiepileptics with
      hepatic enzyme induction potential (carbamazepine, phenytoin) enhance the
      metabolism of sexual steroids. Valproic acid as an enzyme inhibitor and drug with
      high protein binding affinity elevates the free serum levels of androgens.
      Certain antiepileptic drugs may have negative cognitive side effects, some of
      them can induce psychiatric disorders. These drugs can facilitate male sexual
      dysfunctions through these psychic side effects. The metabolic and endocrine
      alterations caused by carbamazepine may return to normal level after replacement
      of carbamazepine with oxcarbazepine. After an oxcarbazepine-carbamazepine
      replacement, carbamazepine-induced impotency can be cured. According some new
      data lamotrigine can also help in sexual dysfunction. The therapy of sexual
      dysfunction in epilepsy depends on its cause. In cases of hormonal alterations,
      the fist step is a change of antiepileptic regimen. Instead of enzyme-inductor
      antiepileptics and valproate, new antiepileptic drugs should be prescribed. At
      present, the most investigated antiepileptic drug is the oxcarbazepine with
      positive effect on antiepileptic-induced male sexual dysfunction, however,
      lamotrigine seems to be also beneficial. If the hormonal and sexual dysfunctions
      cannot be eliminated by drug changes, androgenic therapy or bromocriptine may be
      required. Testosterone may not only be beneficial on sexual functions, but can
      reduce also the seizure frequency. Independent of etiology, erectile dysfunctions
      can be successfully treated by sildenafil.

PMID- 16786710
TI  - [Significance of neutralizing antibodies to immunomodulatory therapy and their
      laboratory analysis in multiple sclerosis].
AB  - Interferon-alpha, -beta, and -gamma have been used for the management of several
      diseases with varying clinical effects. Like many other proteins, all interferon
      species are potentially immunogenic, especially those produced by recombinant
      gene technologies. A reliable screening assay for anti-interferon-beta antibodies
      is suggested for patients with multiple sclerosis receiving interferon-beta
      therapy. Natural interferon-beta is a glycosylated 166 amino acid 25 kDa protein,
      recombinant interferon-beta is available for therapy as 1a and 1b products. Both
      preparations induce anti-interferon-beta antibodies, detectable in the serum of
      interferon-beta-treated patients with multiple sclerosis. The question of which
      assay is optimal for testing for anti-interferon-beta antibodies in interferon
      beta-treated patients is unsettled. Two types of antibody assays are generally
      used: those measuring binding antibodies and those measuring neutralizing
      antibodies. The findings suggest that high titers of both binding and
      neutralizing antibodies reduce the clinical efficacy of interferon-beta in
      relapsing-remitting multiple sclerosis, which is important for the long-term
      efficacy of these drugs. Treatment with glatiramer acetate has also been shown to
      induce the development of "reactive antibodies" in patients with multiple
      sclerosis. This article briefly describes some of the findings concerning anti
      interferon binding and neutralizing antibodies.

PMID- 16786711
TI  - [Neuropathologic investigation in autopsies with special emphasis on findings in
      Alzheimer's disease].
AB  - Out of an average total of 1400 autopsies per year, neuropathological
      examinations were performed in 477 cases between 1997 and 1999 to investigate the
      incidence of dementias. The majority of the studied subjects were over 50 years
      old. Bielschowsky's and/or Gallyas's silver methods and, in some cases, protein
      tau (MAP) immunocytochemistry and amyloid staining were performed beside routine
      examination. Pathological changes were found in 212 of the 364 cases studied by
      the above methods but histological changes associated with dementia were only
      detected in 167 cases. The various forms of Alzheimer's dementia were also
      classified by age. The "incipient" form of Alzheimer's disease was verified in 23
      cases. Old infarcts of various extensions were found in 42 percent of Alzheimer's
      dementias. Very mild or age-related degenerative changes were observed in 82
      cases among subjects over 50 years old. Of these, eight patients died in their
      90s. In some cases (n = 38) the number of neuritic plaques dominated over the
      number of neurofibrillary tangles but a reverse finding also occurred (n = 13).
      Neuronal degeneration was variable and was not always proportional to the number
      of neurofibrillary tangles. "Simple type of senile atrophy" was defined by the
      presence of minor or age-related Alzheimer changes and was considered a separate
      entity. The "incipient" form of Alzheimer's dementia was diagnosed in relatively
      young individuals where mild Alzheimer changes were found at the
      neuropathological examination. "Preclinical" Alzheimer's dementia could only be
      suspected by clinical data and could very rarely be supported by the
      neuropathological finding of "incipient" form. The ratio of pure Alzheimer's to
      vascular dementias cases proved to be 54:41 in this study. The results suggest
      that dementias are considerably underdiagnosed both in the clinical and
      pathological practice and that the recently defined "preclinical" and "incipient"
      forms are very hard to recognize both clinically and pathologically. The
      neuropathological study of the degenerative, mainly Alzheimer's type, findings in
      the randomly selected autopsies revealed great variations which raises many
      questions concerning the normal and pathologic aging of the brain as well as the
      "incipient" and senile forms of Alzheimer's dementia.

PMID- 16786712
TI  - [Experience with levetiracetam in childhood epilepsy].
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam in children
      with drug resistant epilepsy from a retrospective study. METHODS: We report the
      result of a study of 85 pediatric patients (mean 10.5 years, range: 1-24) with
      refractory generalized and focal epilepsy, who received levetiracetam as add-on
      treatment. The average duration of epilepsy was eight years, and the patient were
      treated with mean of 6.0 antiepileptic drugs before levetiracetam was introduced.
      RESULTS: Ten patients (12%) became seizure-free, three (3%) responded with
      seizure reduction of more than 90%, 32 (38%) responded with seizure reduction of
      more than 50% following introduction of levetiracetam. No response to
      levetiracetam was reported in 34% (n: 29). Positive psychotropic effect was
      observed in 26 patient (30%). Mild to moderate side effects were reported in 11
      patients (13%), consisting most frequently general behavioral changes,
      aggression, sleep disturbances, but they ceased after decreasing the dose of
      levetiracetam. Mental retardation was associated with poor response and
      associated with more side effects. CONCLUSION: Levetiracetam is a well tolerated
      new antiepileptic drug that may effectively improve seizures control as an add-on
      drug in resistant epilepsy in childhood with good tolerability.

PMID- 16786713
TI  - [Changes in EEG-complexity after subcortical ischemic brain damage].
AB  - INTRODUCTION: Complexity analysis of the EEG is a relatively new field in
      theoretical and clinical electrophysiology. The authors present results of EEG
      analysis in a patient with stroke, utilizing the sensitivity of the new
      procedures with respect to linear and nonlinear synchronization. PARTICIPANTS AND
      METHODS: The EEG (19 channels) was recorded in a patient with subcortical
      unilateral ischaemic completed stroke involving the frontoparietal white matter
      while leaving the cortex intact and in 12 healthy controls in eyes open and in
      eyes closed conditions. RESULTS: In the patient, increased Omega-complexity was
      found in slow (delta, theta) and lower alpha frequencies in the side of the
      stroke and in high frequencies (beta2 in eyes closed, alpha2, beta1 and beta2 in
      eyes open conditions) in the intact side. Synchronization likelihood was higher
      in the ischaemic side in the beta2 (eyes closed) and both in the beta1 and beta2
      (eyes open) frequencies. Increasing Omega-complexity caused by eyes opening was
      markedly reduced in the patient in the beta frequencies compared to that seen in
      the controls. The difference was more conspicuous in the side of the infarct and
      involved not only the beta but also the alpha frequencies as well. Opening the
      eyes decreased synchronization likelihood in all frequency bands in the controls
      and also in the patient except the alpha2, beta1 and beta2 bands in the side of
      the lesion. CONCLUSIONS: The increased Omega-complexity and decreased
      synchronization likelihood in the slow frequencies in the infarcted side is
      probably the result of lesioned interneuronal connections lowering the level of
      cooperation of neuronal systems involved in this type of activity. The increased
      Omega-complexity and decreased synchronization likelihood caused by eyes opening
      could not be observed in the beta and alpha frequencies in the side of the
      lesion, possibly caused by damaged thalamocortical connections.

PMID- 16786714
TI  - [Complex eye movement disturbance in thalamic and mesencephalic infarcts].
AB  - A 36 year-old male patient developed sudden double vision and gait imbalance.
      Neurological examination revealed gaze paresis upward and on the left side
      downward (vertical "one-and-a-half"-syndrome), horizontal gaze nystagmus on the
      left bulbus directed to left. The MRI revealed bilateral thalamic and left
      midbrain ischemic lesions. The brainstem auditory and visual evoked responses
      were normally configured. Optokinetic nystagmus test found rightward, upward and
      downward hypometric saccades, convergence-retraction nystagmus--which was not
      visible at physical neurological examination--saccadic smooth pursuit eye
      movement and pseudoabducent palsy on both sides. The complex gaze disturbance was
      attributed to the lesions in the intralaminar nuclei of the thalamus and in the
      pretectal and rostromedial tegmentum of the mesencephalon. Infarcts may have been
      due to a variant artery: i.e. the thalamoperforant and the superior paramedian
      mesencephalic arteries originate with common branch from one of the communicant
      basilar artery. The authors discuss the mechanism of complex gaze palsy and call
      attention to the diagnostic value of optokinetic nystagmus examination.

PMID- 16786715
TI  - [The beginnings of anthropology in Hungary].
AB  - In the second half of the 19th century anthropological research started
      everywhere in the world. Cranioscopy formed an important part of physical
      anthropology. Jozsef Lenhossek (1818-1888) worked also on this subject and on the
      basis of one of his investigations in 1875 he became the founder of physical
      anthropology in Hungary. On 76 skulls of several collections and on 265 heads
      together with his coworkers he performed 50 measurements on each skulls and heads
      and calculated the important ratios (skull-indexes). He determined the skull
      indexes of the Hungarian people. These indexes are valid also today.

PMID- 16786716
TI  - IPA uses risk-adjusted profiling to reduce utilization.

PMID- 16786717
TI  - Clinical paths, subcapitation, DM effective for California multispecialty IPA.

PMID- 16786718
TI  - Patients not alarmed when capitation disclosed as method of physician
      compensation.

PMID- 16786719
TI  - Better access to primary care may reduce ED use in Medicaid managed care.

PMID- 16786720
TI  - Relationship between the prostatic tissue components and natural history of
      benign prostatic hyperplasia.
AB  - OBJECTIVE: Few reports have been published on the relationship between prostatic
      tissue components and the natural history of benign prostatic hyperplasia (BPH).
      The present study was undertaken to evaluate this relationship. STUDY DESIGN:
      Forty-nine patients with BPH who underwent suprapubic prostatectomy were studied.
      Six infant prostates and 10 non-BPH specimens were obtained from autopsy.
      Specimens were stained with antibodies to alpha-smooth muscle actin, and the mean
      ratio of the stroma was determined with computer image analysis. Stromal ratios
      were evaluated according to resected prostate weight and age. RESULTS: The stroma
      comprised 82.6 +/- 8.4% of the prostate area at 0-1 year of age and 43.7 +/- 5.1%
      at 15-28 years of age. In BPH, the stromal proportion increased to 55.9 +/-
      10.2%, but decreased with increases in prostate weight and/or age. CONCLUSION:
      The stromal component increased in patients with BPH and decreased with increased
      prostate weight and/or age, comprising approximately 42-47% of the prostate area,
      as in the non-BPH prostate, indicating a balance in prostatic tissue components
      in both patients with BPH and the non-BPH prostate.

PMID- 16786721
TI  - Prostate basal cell lesions can be negative for basal cell keratins: a diagnostic
      pitfall.
AB  - BACKGROUND: Prostate basal cell lesions can have architectural and cytologic
      atypia that mimic prostate adenocarcinoma. Immunohistochemical stains for basal
      cell markers are most helpful in the differential diagnosis. All of the published
      studies show basal cell lesions are positive for basal cell keratins, whereas
      adenocarcinoma is negative for both. We reported two cases of prostate basal cell
      lesions with negative basal cell keratin expression by immunohistochemistry.
      STUDY DESIGN: We reported the histologic and immunohistochemical profiles of two
      cases of basal cell lesions of the prostate. RESULTS: Histologically, both cases
      were highly suspicious for prostate adenocarcinoma with infiltrative growth
      pattern and significant nuclear atypia. The atypical glands in both cases were
      negative for basal cell keratins. However, both lesions were positive for another
      basal cell marker, p63, confirming that they were basal cells in origin, rather
      than prostate adenocarcinoma. CONCLUSION: Prostate basal cell lesions can
      occasionally be negative for basal cell keratins by immunohistochemistry and
      therefore may be misdiagnosed as prostate adenocarcinoma. We recommend using both
      p63 and basal cell keratins simultaneously in the workup of atypical prostate
      lesions to avoid such a misdiagnosis.

PMID- 16786722
TI  - Usefulness of AgNOR technique and CEA expression in atypical metaplastic cells
      from cervical smears.
AB  - OBJECTIVE: To evaluate the proliferating capacity of atypical metaplastic cells
      in cervical smears by AgNOR technique and image analysis and investigate the
      probable relation with squamous intraepithelial lesions (SIL) using
      immunocytochemical assay for carcinoembryonic antigen (CEA). STUDY DESIGN: Eight
      cervical smears were stained with Papanicolaou stain for diagnosis of atypical
      metaplastic cells. After removal of the stain the smears were processed with a
      silver colloidal solution and the AgNOR area determined by image cytometry.
      Differences in the mean AgNOR protein area between reactive metaplastic cells and
      controls were tested by Student's t test. The CEA was investigated by
      immunocytochemical staining in smears with atypical metaplastic cells and smears
      from high-grade squamous intraepithelial lesions (HSIL). RESULTS: The mean AgNOR
      areas from atypical metaplastic cells (4.55, 6.66, 4.68, 5.30, 4.97, 6.20, 6.28,
      and 7.35) were significantly greater those that of intermediate metaplastic cells
      and cells from low-grade squamous intraepithelial lesions (LSIL) (0.77, 0.99, and
      0.82, respectively). The atypical metaplastic cells showed values of mean AgNOR
      area intermediate between that of basal cells (3.28) and HSIL cells (7.73) or
      neoplastic cells (16.12). The CEA was strongly expressed by the atypical
      metaplastic cells. CONCLUSION: The expression of CEA in the atypical metaplastic
      cells underlies the probable relation to SIL. Although the organizer region areas
      raised high values, it would be necessary to use a greater number of cases to
      define whether the AgNOR area is indicative of the proliferative activity of the
      atypical metaplastic cells.

PMID- 16786723
TI  - Gastrointestinal stromal tumor. A study of 158 cases: clinicopathological
      features and prognostic factors.
AB  - OBJECTIVE: To increase knowledge on the behavior of gastrointestinal stromal
      tumors (GISTs) and factors influencing therapy. STUDY DESIGN: The
      clinicomorphological features of 158 GISTs were analyzed. Survival analysis was
      performed on the whole series, as well as on a selected group of patients with
      high risk GIST who did not receive imatinib mesylate. The impact of imatinib
      mesylate on the prognosis was investigated. RESULTS: Most of the GISTs had a
      benign behavior. The risk class was a powerful prognostic factor but was unable
      to predict the outcome in a single case; even patients in the high risk class not
      receiving imatinib mesylate had a low mortality rate. In this group, it was the
      mitotic activity that better correlated with prognosis, and a cut point of 10
      mitoses per 50 high-power field can be fixed to discriminate cases with favorable
      or unfavorable outcome. Patients with GISTs presenting as aggressive disease
      received great benefit from imatinib mesylate therapy. CONCLUSION: Mitotic
      activity is important in predicting the outcome of patients with high risk GIST
      who present at diagnosis without dissemination. This finding can have therapeutic
      implications.

PMID- 16786724
TI  - Flow cytometry phenotypization of thyroidal lymphoid infiltrate and functional
      status in Hashimoto's thyroiditis.
AB  - OBJECTIVE: To evaluate the thyroidal lymphoid infiltrate (TLI) in thyroidal
      functional status (TFS) for differences among patients with Hashimoto's
      thyroiditis (HT). STUDY DESIGN: Flow-cytometry (FC) was applied to thyroidal fine
      needle cytology samples in 57 patients. TLI was analyzed using a fluorescence
      activated cell sorter (FACS) scan and fluorescence antibodies CD3, CD4, CD5, CD8,
      CD10, and CD19 and kappa and lambda light chains. TFS was determined by serum
      thyroid-stimulating hormone (TSH), FT3 and FT4 immunoassays, in specific clinical
      settings, to classify the cases as hyperthyroid, euthyroid and hypothyroid. FC
      assessment was then compared with the corresponding TFS. RESULTS: B-lymphocytes
      were present in 44 cases (77%). T-lymphocytes were present in all the cases;
      CD4/CD8 = 2:1 ratio was observed in 16 euthyroid, 1 hyperthyroid and 3
      hypothyroid; CD4/CD8 > or = 3:1 ratio in 22 euthyroid, 2 hyperthyroid and 2
      hypothyroid cases; CD4/CD8 < or = 1:1 ratio in 1 euthyroid, 3 hyperthyroid and in
      7 hypothyroid cases. Grouping hyperthyroid and hypothyroid cases, a significant
      association was observed with the CD4/CD8 < or = 1:1 ratio (p < 0.01).
      CONCLUSION: Intrathyroidal CD4/CD8 < 1:1 ratio might be the expression of intense
      apoptosis in the early phases of HT, generally followed by the restoration of
      CD4/CD8 balance; persistence of increased intrathyroidal CD8 might be related to
      intense thyroidal damage and thus an increasing risk of hypothyroidism.

PMID- 16786725
TI  - Intratubular germ cell neoplasia of unclassified type.
AB  - Intratubular germ cell neoplasia of unclassified type (IGCNU) is the precursor
      lesion of adult testicular germ cell invasive tumors. Primordial germ cells
      (PGCs) are recognized as the cells of origin of testicular germ cell tumors
      (TGCTs) because of the genetic and phenotypic characteristics analyzed. The most
      important risk factors responsible for abnormal development of PGCs are
      environmental, including the testicular dysgenetic syndromes that generate a
      better microenvironmentfor survival of IGCNU cells, an abnormal relationship with
      Sertoli cells, and an abnormal hormonal exposure at the time of testicular
      differentiation in utero. Furthermore, a familial TGCT susceptibility gene
      (TGCT1), localized at Xq27, is associated with a higher risk for bilateral tumors
      and possibly cryptorchidism. The normal tetraploid pattern and the consequent
      genomic instability of germinal cell DNA are considered sufficient per se for
      neoplastic transformation. The altered expression of oncogenes and suppressor
      genes due to nonrandom chromosomal numerical aberrations are involved in the
      development of IGCNU. Some of these genes are considered responsible for
      bilaterality, while other genes characterize the similarity between IGCNU cells
      and PGCs or are involved in the neoplastic transformation, histotype
      differentiation, and invasivity. In spite of the monomorphic seminomatous
      appearance of cells in IGCNU, it is becoming increasingly evident that they hide
      an intrinsic heterogeneity capable of committing neoplastic cells to an embryonal
      and pluripotent development associated or not with a seminomatous phenotype.

PMID- 16786726
TI  - Correlation between the papanicolaou stain and the Wright-Giemsa stain in body
      fluids: a quality assurance study.
AB  - OBJECTIVE: To compare the use of Papanicolaou and Wright-Giemsa stains for the
      evaluation of body fluids in cytology and hematology laboratories and determine
      whether other factors account for discrepancies in diagnosis. STUDY DESIGN: We
      retrospectively reviewed cytopathology reports of peritoneal, pleural, and
      cerebrospinal fluids received by hematology and cytology laboratories for 1 year.
      Cases were divided into 3 categories-benign, atypical, and malignant--and slides
      of discrepant diagnoses were reviewed. RESULTS: During this period, 198 of 3212
      (0.61%) cases received by the hematology laboratory and 252 of 4402 (0.57%) cases
      received by the cytology laboratory were diagnosed as malignant or atypical. Of
      3212 cases simultaneously received by the cytology and hematology laboratories,
      17 diagnosed as malignant by hematology were diagnosed benign by cytology
      (sensitivity 96%). Sixteen cases diagnosed as malignant by cytology were
      diagnosed as benign by hematology (sensitivity 97%). No benign cases were
      diagnosed as malignant (specificity 100%). Review of the glass slides of the
      discrepant cases revealed 8 cases undercalled by hematology and 7 cases
      undercalled by cytology. CONCLUSION: Papanicolaou stain is superior for carcinoma
      and Wright-Giemsa stain for hematopoietic disorders, but used together they may
      reduce false negative results. Delays in processing, staining technique, and
      interobserver variability contribute to discrepancy.

PMID- 16786727
TI  - Sensitivity and specificity of the micronucleus test in hypotonic-swollen
      mononuclear leukocytes compared to the micronucleus test in binucleated
      lymphocytes to assess chromosomal breaks.
AB  - OBJECTIVE: To examine the sensitivity and specificity of the micronucleus (MN)
      test on swollen mononuclear cells compared to that in binucleated lymphocytes.
      STUDY DESIGN: This is a cross-sectional experimental study. Samples were taken
      from patients who had a malignancy who were scheduled to receive chemotherapy;
      samples were taken before and after the chemotherapy regimen began. The MN tests
      on swollen mononuclear cells and binucleated lymphocytes were performed on every
      sample. Proportions of micronucleated cells/cells screened were noted and
      interpreted as positive or negative results. The results of both tests were
      compared to get the sensitivity and specificity of the MN test on swollen
      mononuclear cells. RESULTS: Of 59 samples obtained, 54 were included in this
      study. The results showed that the sensitivity of the MN test on swollen
      mononuclear cells compared to that on binucleated lymphocytes was 89% and
      specificity was 78%. CONCLUSION: The MN test on swollen mononuclear cells was
      able to detect chromosomal breaks caused by chronic clastogen exposure.

PMID- 16786728
TI  - [Nutrition transition: a review of Latin American profile].
AB  - The nutrition situation has evolved in different ways in Latin-American
      countries. The aim of the study was to analyze the nutritional change and some
      conditions within Latin America in the last years. An electronic and manual
      search of articles published between 1995 and 2005 was made, selecting those that
      included the nutritional situation of Latin American countries. Additionally,
      data was collected from national surveys and international reports including
      information since 1990. The countries have evolved through different transition
      stages. For example, an increase of excess of weight, particularly in adult
      women, which exceeded 30% in some countries also reached up to 70% in others.
      Equally worrisome was the over 6% obesity level in children in five of the
      countries surveyed. There is a tendency to diminish the deficit of weight with
      seven of nine countries displaying a reduction of women with low weight while
      stunting diminished globally. An increase of the caloric availability in 17 of 20
      countries was also observed. The total population that lives under the poverty
      line has diminished in 9 of 13 countries although some exceeded 60%. Some
      indicators of sedentary lifestyle have increased, the number of cars has been
      increasing in all countries and similar figures are recorded with respect to
      television and personnel computers. The evolution of the nutritional status is
      reflected through the action of set factors, the most important of which being
      the increase in caloric ingestion and sedentary activities in an urbanized
      environment, the promotion of the use of technologies that limit physical
      activity. There is also a reduction in food insecurity due to a fall in poverty
      levels although social inequalities still persist.

PMID- 16786729
TI  - [Trans fatty acids: foods and effects on health].
AB  - Trans fatty acids can be found in foods derived from ruminant animals and foods
      that contain partially hydrogenated fat such as fast foods. The consumption of
      trans fatty acids is larger in the United States, Canada, and some European
      countries than in Japan and Mediterranean countries. The incidence of coronary
      heart diseases is higher in countries where the consumption of trans fatty is
      high. Studies show that trans fatty acids can contribute to increase LDL and
      lipoprotein [a], and to reduce the levels of HDL. In addition, trans isomeric
      seems to inhibit the action of desaturase enzymes of essential fatty acids (A5-
      and A6-desaturase) by holding back the biosynthesis of important fatty acids such
      as arachidonic acid and docosahexaenoic acid (DHA). With respect to pregnant
      women's and infant's health, concentrations of trans fatty acids ingested by the
      mother are associated to concentrations found in the maternal milk. Besides the
      milk, the trans fatty acids can be transferred to the newly born through the
      placenta. Studies suggest that trans fatty acids can affect intrauterine growth
      due to the inhibition of the conversion of essential fatty acids by desaturase
      enzymes. The inhibition of DHA can also cause early atherosclerosis lesion.
      However, studies on the effects of trans fatty acids on health are still
      inconclusive and there are no current recommendations on their consumption.
      Additionally, in Brazil, studies to determine the composition of trans isomeric
      in foods are still incipient, which indicates a great need of research in this
      area.

PMID- 16786730
TI  - [Lipid profile in Venezuelan preschoolers by socioeconomic status].
AB  - Epidemiological studies have shown that unfavorable serum lipids levels in
      childhood are predictors of development of atherosclerosis lesions in adulthood.
      We assessed the lipid profile of 297 Venezuelan preschool children (4-7 years
      old) from two socioeconomic levels in order to compare them by this
      characteristic. Their social level was determined according to modified Graffar
      method, and two groups were obtained: high socioeconomic status (HSES, n=103) and
      low socioeconomic status (LSES, n=194). Nutritional anthropometric evaluation was
      performed by weight to height, and NCHS/OMS cut-off point was used. Lipid profile
      was determined by colorimetric biochemical methods and atherogenic risks factors
      were calculated. Underweight for HSES was 5.8% and for LSES: 14.9%, while normal
      status was 78.6% and 70.1%, and overweight was 15.5% and 14.9%, respectively.
      Mean values for triglycerides were 0.66 +/- 0.27and 0.76 +/- 0.31 mmol/L, total
      cholesterol (TC): 3.61 +/- 0.65 and 2.98 +/- 0.71 mmol/L, HDL-C: 1.04 +/- 0.18
      and 0.62 +/- 0.16 mmol/L, LDL-C: 2.27 +/- 0.61 and 2.01 +/- 0.71 mmol/L, TC/HDL
      C: 3.5 +/- 0.78 and 5.0 +/- 1.5; LDL-C/HDL-C: 2.0 +/- 0.71 and 3.4 +/- 1.4 with
      significant differences between HSES and LSES as shown respectively. A
      significant association was found (p < 0.01) between lipid values and
      socioeconomic status, being the LSES preschoolers those with the higher
      atherogenic risk. Its pattern was of lower HDL-C levels, and higher TC/HDL-C and
      LDL-C/HDL-C ratio. Comparisons of lipid profile by nutritional status or gender
      did not show significant differences. Findings indicate that children from low
      socioeconomic status are at a higher risk for cardiovascular disease and
      atherosclerosis than children from high socioeconomic status.

PMID- 16786731
TI  - [Serum insulin, leptin and growth hormone levels are associated with body mass
      index and obesity index in adolescents].
AB  - Leptin, insulin and growth hormone levels seem to regulate body composition, fat
      distribution and fat mass. The purpose of this study was to determine the
      relationship among insulin, leptin and growth hormone levels in a group of
      adolescents. Ninety five adolescents (31 boys and 64 girls) between 13 and 18 y.
      of age were studied. A medical and nutritional history was made which included
      body mass index (BMI) and subcutaneous skinfolds measurements. Basal levels of
      glucose, triglycerides, total cholesterol, HDL-C, LDL-C, VLDL-C, leptin, insulin
      and growth hormone were determined. The leptin and insulin levels were positively
      associated with body mass index (BMI) and obesity index (OBI). Insulin, leptin
      and obesity markers were negatively associated with growth hormone level. Fifty
      two percent of the adolescents with BMI = 21.09 kg/m2 were considered
      metabolically obese because they had elevated levels of insulin (18.68 +/- 1.52
      vs. 10.08 +/- 0.38 microU/ml), HOMA IR (3.34 +/- 0.24 vs. 1.76 +/- 0.07), leptin
      (16.30 +/- 1.24 vs. 8.11 +/- 1.32 ng./dl) and triglycerides (78.56 +/- 4.38 vs.
      64.39 +/- 5.48 mg/dl) and lower levels of HDL-C (39.09 +/- 1.27 vs. 43.30 +/-
      2.38 mg/dl), compared with normal group. The same alterations were observed in
      the obese group, in which significative decrease in growth hormone level was
      added. We conclude that hyperinsulinemia, hyperleptinemia and low growth hormone
      levels, may be established as risk factors related to obesity markers, lipid
      alterations and insulin resistance that can lead to an early development of Type
      II diabetes and cardiovascular disease.

PMID- 16786732
TI  - [Lowering plasma homocysteine with vitamins B6, B12, and folic acid. Effect on
      lipids concentration in patients with secondary hyperlipoproteinemia type IV,
      with and without Lovastatina treatment].
AB  - The concentration of plasma homocysteine was diminished by the oral use of
      vitamins B6 (300 mg/day), B12 (250 microg/day) and folic acid (10 mg/day), and
      the effect was studied in the lipids of patient with hiperlipoproteinemia
      secondary type IV, during 120 days, in 30 patients, 45 to 70 years old, with
      myocardial heart attack. They were divided in group A (n=15) without treatment
      with Lovastatin and group B (n=15) with Lovastatin. Basal homocysteine
      concentration was 17.4 +/- 1.0 micromol/L and 16.7 +/- 1.0 micromol/L for the
      groups A and B respectively, diminishing 24% at the end of the experimental time,
      in both groups. Total cholesterol decreased below 220 mg/dl, while the
      triglycerides diminished 25.4 mg/dl and 27.0 mg/dl in groups A and B
      respectively, by each micromol/L of homocysteine catabolissed. Low density
      lipoproteins (LDL) and very low density (VLDL) diminished significantly (p <
      0.005), while the high-density (HDL) increased 1.0 mg/dl in group A and 1.15
      mg/dl in group B, for each micromol/L of homocysteine metabolized, lowering the
      coronary risk factor in 28.5% group A and 35.9% group B. We concluded that these
      vitamins decreased plasma homocysteine concentration, promoting the lowering of
      lipids and lipoprotein concentratation in this type of patients; while Lovastatin
      doesn't reduce homocysteine, but it had a synergic effect with the vitamins,
      dicreasing the lipid concentration, in group B.

PMID- 16786734
TI  - [Microbiological assessment of the Gouda-type cheese-making process in a
      Venezuelan industry].
AB  - The adoption of the Hazard Analysis and Critical Control Point (HACCP) system is
      necessary to assure the safety of the product in the cheese-making industry. The
      compliment of pre-requisite programs as Good Manufacture Practices (GMPs) and
      Sanitation Standard Operating Procedures (SSOPs) are required before the
      implementation of the HACCP plan. GMPs are the standards related to equipments,
      tools, personnel, etc. SSOPs are the procedures related to hygiene and sanitation
      of the plant and workers. The aim of this study was to assess the compliment of
      the pre-requisite programs and the microbiological conditions of the Gouda type
      cheese-making process in a Venezuelan processing plant before designing a HACCP
      plan. Samples were: (a) raw milk, pasteurized milk, curd and ripened cheese, (b)
      water, (c) environment of the production areas and ripening premises, (d)
      equipments before and after sanitation, (e) food handlers. Microbiological
      analyses were done according to COVENIN standards. This study showed that even
      though pasteurization process was effective to kill pathogen bacteria of the raw
      milk and the water was safe, however there are deficient manufacture practices in
      the hygiene as well as in sanitation of the plant and food handlers. Prerequisite
      programs (GMP-SSOP) of this industry need to be well established, controlled and
      evaluated.

PMID- 16786733
TI  - [Effect of diarrhea on nutrient utilization in protein deficient or protein
      calorie deficient rats].
AB  - Diarrhea increases the effects of malnutrition. Accordingly, the effect of
      diarrhea on two types of malnutrition (protein deficiency and protein-calorie
      deficiency) was studied. The experiment included 42 young Sprague Dawley rats.
      The rats were distributed into three groups with 14 rats per group. During the
      first 16 of the experiment, the first group was fed a control diet ad libitum,
      the second received the same diet but with food intake reduced in 50% whereas the
      third group was offered a protein deficient diet. Thus, at the end of this period
      there were well-fed rats (control), as well as protein and protein-calorie
      malnourished rats. Then one half of the rats in each group were given lactose to
      produce diarrhea and all rats continued with their previously assigned diet and
      feeding regime during one more week. Therefore, during this period there were
      control rats, protein deficient rats and protein-calorie deficient rats with and
      without diarrhea. The results showed that diarrhea caused a substantial reduction
      in food intake and growth in the well-fed rats and also in the group fed the
      protein deficient diet. However, the protein-calorie deficient group did not
      reduce its intake nor its growth rate. As a result, diarrhea caused malnutrition
      in the control group and increased malnutrition in the protein deficient but it
      did not have an additional effect in the protein-calorie deficient rats. The
      apparent absorption of lipids and nitrogen measured in these rats showed that the
      absorption reduction caused by diarrhea was more pronounced in the protein
      deficient group. This group also had the lowest activities of intestinal
      disaccharidases. These results showed that diarrhea had a more detrimental effect
      in protein deficient than in protein-calorie deficient rats.

PMID- 16786735
TI  - [Design of a HACCP Plan for the Gouda-type cheesemaking process in a milk
      processing plant].
AB  - The Hazard Analysis and Critical Control Point (HACCP) is a preventive and
      systematic method used to identify, assess and control of the hazards related
      with raw material, ingredients, processing, marketing and intended consumer in
      order to assure the safety of the food. The aim of this study was to design a
      HACCP plan for implementing in a Gouda-type cheese-making process in a dairy
      processing plant. The used methodology was based in the application of the seven
      principles of the HACCP, the information from the plant about the compliment of
      the pre-requisite programs (70-80%), the experience of the HACCP team and the
      sequence of stages settles down by the COVENIN standard 3802 for implementing the
      HACCP system. A HACCP plan was proposed with the scope, the selection of HACCP
      team, the description of the product and the intended use, the flow diagram of
      the process, the hazard analysis and the control table of the plan with the
      critical control points (CCP). The following CCP were identified in the process:
      pasteurization, coagulation and ripening.

PMID- 16786736
TI  - [Thiamine retention as a function of thermal processing conditions: canned
      salmon].
AB  - The present work studied the effect of different treatments at high temperatures
      on the nutritional properties of thiamine retention and color measurement
      experimentally. Canned salmon (Salmo salar) was processed under different
      temperatures and time conditions (110 degrees C for 135 minutes; 114 degrees C
      for 89 minutes; 118 degrees C for 69 minutes and 121 degrees C for 62 minutes).
      Thiamine was determined by HPLC before and after the process. Color changes, due
      to processing conditions, were also measured utilizing a Hunter colorimeter. The
      canning was prepared in 300 x 407 cans and sterilized until Fo value reached 6
      min. The nutritional value or index represented by the B1 vitamin or thiamine was
      affected by high temperature and time exposition. The lowest loss of thiamine of
      19.2% was obtained in the canned salmon sterilized at 114 degrees C for 89
      minutes. The color in canned salmon was different from the raw material, with a
      severe loss of red color and a greater clarity of the meat.

PMID- 16786737
TI  - [Manaca, sweet potato and yam: possible substitutes of wheat in foods for two
      ethnic population in Venezuelan Amazon].
AB  - In this study, flours from manaca or acai (Euterpe oleracea Mart), sweet potato
      (Ipomea batatas), and yam (Dioscorea spp.), species grown in the Venezuelan
      Amazon, were obtained. The proximal composition, water activity (a(w)), Fe, Ca,
      Zn, Mg, Cu, Na and K content were determined for the flours of manaca, sweet
      potato and yam. These flours were used as ingredients of products for the
      inhabitants of the indigenous populations of the Venezuelan Amazon (Piaroa and
      Hiwi). Two types of products that traditionally contain wheat flour in their
      formulation (ingredient they know by transculturation) were formulated; an
      attempt to substitute it totally or partially by the manaca, sweet potato and/or
      yam flours was made. For the selection of the products to be formulated, the
      preferences and eating habits of the indigenous communities and ease and
      simplicity of the preparations to be developed, were considered. The two products
      formulated were cookies and "small cakes". To decide on the formulation(s) of the
      final product(s), sensorial evaluations were made in the laboratory and in the
      indigenous communities Piaroa and Hiwi. High fat content (16%), dietetic fiber
      (59.7%) and iron (25 mg / 100 g) in manaca or acai flour were remarkable. Two
      types of cookies and two of "small cakes" were equally accepted by the indigenous
      communities. Cookies supply a high iron amount (about 24%). The feasibility of
      substituting the wheat flour by manaca, sweet potato and yam flour in products
      accepted by two ethnic populations of the Venezuelan Amazon was demonstrated.

PMID- 16786738
TI  - [Cardon dato (Stenocereus griseus, Cactaceae) fruit pulp as raw material for
      marmalade production].
AB  - This study aimed to examine the possibility of producing marmalades from the
      fruit pulp of the red and white varieties of card6n dato (Stenocereus griseus).
      We developed the formulations of the marmalades and evaluated their stability
      during three months of storage at room temperature. As first step, we
      characterized the fruits of the two color varieties, observing that despite the
      considerable difference between both color varieties, there were no significant
      differences in average weight, dimensions and proportion of pulp, skin and seeds.
      The pulp of the two color types had high pH (5.2) values and low contents of
      reductor sugars (3.59 g/ 100 g white variety 2.23 g/ 100 g red variety), non
      reductor sugars (0.75 g/ 100 g white variety and 2.03 g/ 100 g red variety),
      pectin (0.14 g/ 100 g white variety and 0.23 g/ 100 g red variety) and acids
      (7.67 g/ 100 g white variety and 0.15 g/ 100 g red variety). It is needed to
      include sugar, pectin, and citric acid in the marmalade formula. The first
      marmalades produced were gummy, a problem that we solved adding the acid from the
      beginning of the making process. During the three months of storage, the
      marmalades had good acceptance by the evaluators, this despite slight
      fluctuations observed in pH, solid contents, and acidity.

PMID- 16786739
TI  - [Correlations between serum matrix metalloproteinase (MMP-1, MMP-3, MMP-9, MMP
      13) concentrations and markers of disease activity in early rheumatoid
      arthritis].
AB  - The purpose of this study was to analyse the correlations between serum
      concentrations of the matrix metalloproteinases (MMP-1, MMP-3, MMP-9, MMP-13) and
      clinical markers of disease activity in patients with early rheumatoid arthritis
      (RA). The study group consisted of 30 RA patients, untreated with disease
      modifying antirheumatic drugs (DMARDs) or corticosteroids, with disease duration
      less than 3 years. The analysis of serum concentrations of MMPs was based on a
      quantitative sandwich ELISA. We observed the positive significant correlations
      between studied MMPs and clinical markers of disease activity, such as number of
      swollen joints or erythrocyte sedimentation rate (ESR). Furthermore, we revealed
      significant correlations between serum MMP-1, MMP-3, MMP-9, MMP-13 concentrations
      and disease activity score (DAS) (p < 0.01; p < 0.001; p < 0.001; p < 0.05
      respectively). We conclude that studied matrix metallo-proteinases might be
      useful clinical markers of disease activity in early rheumatoid arthritis.

PMID- 16786740
TI  - [Value of closed pleural biopsy in diagnosis of pleural effusion].
AB  - The aim of the study was to assess closed pleural biopsy (CPB) as a diagnostic
      method of pleural effusion. CPB using Cope needle was performed in 62 patients,
      proceeded by ultrasound examination. It helped to obtain specimen for
      histological and microbiological examination even with cases of small amount of
      fluid. In all 62 patients CPB enabled to diagnose 13 cases with neoplasmatic
      effusions (majority being adenocarcinomas) and 16 cases of tuberculosis in
      histological and/or microbiological examination. There were 33 cases with non
      specific inflammatory changes. In 7 patients we confirmed neoplastic pleural
      infiltrates in cytological examination of pleural effusion. In 26 patients
      videothoracoscopy (VTS) was carried out and 20 of those had post-inflammatory
      changes. In 4 cases, however we confirmed neoplasmatic effusions and in next 2
      cases--tuberculosis. Closed pleural biopsy proves to be an efficient method in
      diagnosis of Tuberculosis and malignant pleural effusions. However, in 23% of
      cases with post-inflammatory changes, malignancy and tuberculosis were
      undiagnosed. This in turn implicates the necessity for further diagnostic
      procedures including VTS.

PMID- 16786741
TI  - [Markers of oxidative balance and concentration of selected metals in
      pollinotics].
AB  - It was reported that catalytically active metals are presented in both the
      soluble and insoluble fractions of ambient air pollution particles. Both
      catalyses generate and stimulate oxidative stress. There are very few reports on
      the role of oxidative stress in pollen allergy Theoretical presumptions may
      suggest that oxidative metabolism can be influenced by the activity of some
      metals and, on the other hand, pollens could be a carrier of at least catalytic
      amount of metals. The aim of our study was to evaluate concentrations of some
      metals (Cd, Cr, Pb, Ni, Mg, Zn) and compare the markers of oxidative balance
      expressed as malondialde-hyde (MDA) concentration, superoxide dismutase (SOD) and
      glutathion peroxidase (GPx) activities in the blood of patients with pollinosis.
      The investigation was performed on the group of 50 individuals, 34 diagnosed as
      pollen allergic and 16 healthy volunteers. We have found Pb blood concentration
      higher in pollen allergics group, but only on the verge of statistical
      significance (p = 0.058). No statistically significant differences in the
      concentrations of other examined metals between pollen allergics and controls
      were observed; whereas SOD activity was higher in allergics (p = 0.015), GPx
      activity lower in allergics (p = 0.045) and MDA concentration higher in allergics
      (p = 0.044). The positive linear correlations between SOD and Pb (r = 0.492; p <
      0.001) as well as between Mg and MDA (r = 0.329; p = 0.02) were observed. On the
      basis of these results we formulated the following hypotheses, in our opinion
      worth further investigations: The statistically significant increase in SOD
      activity in the group of pollen allergics when compared to the group of controls
      points out the role of oxidative stress in pollen allergic persons. The
      statistically significant decrease in GPx activity suggests the long-lasting
      duration of oxidative stress in pollen allergic. The positive correlation between
      SOD activity and Pb level may suggest the putative role of Pb in oxidative
      stress. The positive correlation between Mg and MDA may suggest the presence of
      an additional mechanism in pollen allergy probably connected with the activation
      of phagocytosis by magnesium.

PMID- 16786742
TI  - [Non-allergic type of atopic dermatitis among patients of Allergic Diseases
      Diagnostic Center, University of Medical Sciences in Poznan].
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease of unclear
      etiopathogenesis. It belongs to the group of atopic diseases and an IgE-mediated
      uptake and antigen focusing of environmental allergens by IgE-bearing dendritic
      cells is assumed to be a central immunopathogenetic event resulting in clinical
      appearance of AD. In case of non-allergic (intrinsic) type of AD, non IgE-related
      factors are involved in the process. Potential immunological and clinical
      differences between allergic and non-allergic type of the disease are still being
      investigated. The aim of our study was to evaluate prevalence of non-allergic and
      allergic type of AD among patients of Allergic Diseases Diagnostic Center,
      University of Medical Sciences in Poznan between 2001 and 2002. We investigated
      161 patients with AD and selected factors influencing course of the disease such
      as age, gender, month of birth, population of the region and characteristics of
      sensitizing allergens were analyzed. Allergological diagnostics consisted of skin
      prick tests and measurements of total and antigen specific IgE concentrations in
      sera of investigated patients (FEIA CAP). Non-allergic type of AD was registered
      in 38.5% of the investigated population. There was no significant difference
      between allergic and non-allergic type of AD in terms of month of birth and
      living conditions (urban areas or countryside). Especially in the case of
      children evaluations of total and antigen specific IgE serum concentrations were
      helpful in verification of skin prick test results. In the group of patients with
      allergic type of AD grass pollen allergens were sensitizing most frequently and
      finally type of sensitizing airborne allergens may be at least partially related
      to the environmental characteristics of the region.

PMID- 16786743
TI  - [The results of extra diagnostic methods in patients allergic to dust mites
      treated by specific immunotherapy].
AB  - BACKGROUND: In addition to allergen elimination, specific immunotherapy remains
      the only recognized causal treatment of allergic diseases. Nevertheless, there
      are no commonly accepted parameters and tests allowing for the evaluation and
      prediction of its efficacy. The aim of this study was to evaluate the results of
      readily available supplemental allergy tests and to attempt to associate those
      findings with the outcome of therapy for desensitized patients. METHODS: This
      study was conducted in a group of 22 patients receiving specific immunotherapy
      for perennial allergic rhinitis to dust mites. The results of skin prick tests,
      sIgE levels, nasal eosinophilia levels as well as specific nasal provocation
      tests measured by acoustic rhinometry were compared prior to desensitization and
      two years following the therapy. The control group comprised 17 allergic patients
      treated without immunotherapy. RESULTS: Apart from the confirmation of
      immunotherapy efficacy, a positive correlation between its results and the
      results of the nasal provocation test (correlation coefficient r = 0.85) were
      demonstrated in this study. No relationship was however found between the
      obtained result and the results of skin prick tests (r = 0.57) and serum sIgE
      levels (r = 0.59) or nasal eosinophilia (r = 0.57). The result of acoustic
      rhinometry corresponded well with clinical manifestations observed in nasal
      provocation tests. CONCLUSIONS: The specific nasal provocation test is an easy
      method that may be used for monitoring the efficacy of immunotherapy, and
      acoustic rhinometry is a good method for measuring its results.

PMID- 16786744
TI  - [Exhaled hydrogen peroxide (H2O2) in allergic and non-allergic stable mild
      asthmatic children].
AB  - The evaluation of breath condensate (BC) composition is a new, non-invasive
      method studying inflammation processes in several respiratory diseases. Among
      many inflammation markers, hydrogen peroxide (H2O2) is the most common one, and
      its increased level was found in BC of cystic fibrosis and asthma patients. As in
      children's asthma, H2O2 is present and could correlates with the severity of the
      disease. The aim of our study was to check whether there exist differences
      between levels of H2O2 in children with allergic and non-allergic asthma. 83
      allergic and 33 non-allergic children with mild asthma (50 girls and 66 boys,
      aged 7-17 years) were included in the study. All patients were clinically stable
      and used inhaled corticosteroids daily, and an inhaled bronchodilator on demand.
      Exhaled BC was obtained by spontaneously tidal volume breathing with EcoScreen
      (Jaeger, Germany). The content of H2O2 in the BC was measured
      spectrofluorometrically (homovanillic acid method). All subjects underwent flow
      volume measurements immediately after collection of the condensate. Lung function
      in asthmatic allergic and non-allergic children showed near normal values and did
      not differ between groups. In the allergic group, the median H2O2 level in the
      expired condensate was 0.238 (0-1.86) microM, and in non-allergic 0.192 (0-0.78)
      microM (p > 0.05). We conclude that hydrogen peroxide in exhaled breath
      condensate of children with stable mild asthma does not differ significantly in
      allergic and non-allergic children and activity of airway inflammation seems to
      independent on allergic status of patients.

PMID- 16786745
TI  - [Ultrasonographic evaluation of atherosclerotic changes in carotid and brachial
      arteries in obese and hypertensive children].
AB  - According to very well documented onset of atherosclerosis in early childhood,
      scientists are looking for good diagnostic methods for evaluating first changes
      in arterial blood vessels noninvasively. We want to know more about pathogenetic
      mechanisms and about changes in vessels especially in the group of young people
      with risk factors of premature atherosclerosis. The role of endothelial
      dysfunction in the very early phase of this process is known well so far. High
      resolution echocardiography seems to be a good method which allows to examine
      arteries in children and adolescents. Because of localization, brachial and
      carotid arteries are a very good field for this kind of examinations. The aim of
      this study was the evaluation with high resolution echocardiography, selected
      parameters of endothelial function in obese and hypertensive children and
      adolescents. We measured the intimal plus medial thickness in carotid common
      arteries (IMT) also. MATERIAL AND METHODS: We examined a group of 54 children (33
      boys and 21 girls) aged 13-15 yr (mean 14 yr 6 months) obese or/ and with
      arterial hypertension. We eliminated persons with secondary reasons for these
      risk factors. For better analizes we devided a whole group into 3 subgroups:
      patients with isolated arterial hypertension (n-20), with isolated obesity (n-15)
      and with cumulation of both factors together (n-19). The control group consisted
      of 17 children (11 boys, 6 girls) in similar age. Using high resolution
      echocadiography, B-mode images, we measured during end diastole, distance "m-m"
      in brachial arteries (distance between two "m" lines which borde with media and
      adventitia of near and far wall of the artery) at rest, during reactive hyperemia
      (with increased flow causing endothelium-dependent dilatation FMD), again at rest
      and after sublingual administration glyceryl trinitrate (causing endothelium
      independent dilatation NTGMD). Using Doppler technic we evaluated baseline flow
      and calculated degree of reactive hyperemia. We also measured intimal plus medial
      thickness in every carotid artery three times and calculated mean value. In our
      analysis we estimated concentrations of cholesterol, HDL-cholesterol, LDL
      cholesterol and triglicerides. RESULTS: In the whole examined group, the vessel
      size was larger and FMD was significantly impaired. In the group with an isolated
      hypertension and isolated obesity we noticed some differences but they did not
      achieve statistical significance. In the group with cumulation of risk factors,
      the "m-m" value, was significantly higher at rest, during reactive hyperemia and
      after medication and FMD was significantly lower. NTGMD in all subgroups was
      similiar to control group. We noticed higher IMT values in the whole examined
      group and in the subgroups compared to the control group. The highest IMT were in
      the case of the cumulation of hypertension and obesity. The level of
      triglicerides was higher in the group of isolated obesity, with obesity and
      hypertension and in whole examined group against control. CONCLUSIONS: 1. FMD
      evaluated in brachial artery, seems to be usefull in diagnosis of impaired
      endothelial function in young people suffering from the risks factors of
      athersclerosis. 2. Isolated obesity or arterial hypertension did not influence
      significantly on the impairing of endothelial function. 3. The degree of
      impairment in endothelial function is dependent on accumulation of athersclerosis
      risk factors (obesity and hypertension). 4. The evaluation of IMT in carotid
      arteries in children with obesity and hypertension, showed more advanced degree
      of atherosclerotic changes in this group compared to healthy controls.

PMID- 16786746
TI  - [Measles incidence in the cohort of schoolchildren and vaccination
      effectiveness].
AB  - The purpose of the study was to assess measles incidence in the cohort of
      schoolchildren and vaccination effectiveness. Subjects under study covered 1005
      children in the aged of 11 years, who were covered by the prospective
      epidemiological study in Krakow. The results of the study have demonstrated that
      78% of children received full vaccination, 18% underwent incompleted vaccination,
      while only 4% did not receive any vaccination against measles. Cumulated
      incidence in the total group was 12%, but in the unvaccinated it was 4 times
      higher (41%) than in the vaccinated group of children (9%). In the group with
      incomplete vaccination, cumulative incidence was 17%. Effectiveness of
      uncompleted vaccination was 58% and that of the complete vaccination reached 78%.
      When additional variables were included in the multivariate logistic models such
      as children health status and potential errors of medical diagnosis, estimated
      effectiveness of current vaccination program was higher than 90%.

PMID- 16786747
TI  - [The total antioxidative activity measured by FRAP method in women with
      intrauterine growth restriction treated by L-arginine].
AB  - The total antioxidative activity means the organisms ability to defend against
      free radical reactions. This can be changed in pathological pregnancies. DESIGN:
      The aim of the study was to find the correlation between total antioxidative
      activity in the serum of healthy pregnant women and in intrauterine growth
      restriction. The decrease of total antioxidative activity may be connected with
      high risk of cell membrane destruction. High risk of destruction of different
      biological cell functions by free radical processes is observed in IUGR and
      hypertension. MATERIAL AND METHODS: The study was taken in Medical University in
      Lodz in 1999-2003. The study group consists of 80 women with IUGR, the controls
      of 60 healthy pregnant women. L-arginine - nitric oxide precursor and
      acetylsalicylic acid were used in the group of IUGR. The total antioxidative
      serum activity was measured by FRAP method and expressed in mmol/l. RESULTS: In
      IUGR group total antioxidative activity was lower before treatment and it
      increases after the treatment. In controls, the value was higher than in IUGR
      group before and after the treatment. CONCLUSIONS: The significant difference
      between two groups and the increase of total antioxidative activity in IUGR due
      to the L-arginine treatment was found.

PMID- 16786748
TI  - [Influence of cardiopulmonary bypass on risk of AF after coronary artery bypass
      grafting].
AB  - Atrial fibrillation is the most common tachyarrhythmia after coronary artery
      bypass grafting. The etiology of this arrhythmia and factors responsible for its
      genesis are unclear. The aim of this study was to compare the frequency of AF in
      patients undergoing coronary artery bypass grafting without the use of
      cardiopulmonary bypass (CPB) with those undergoing CABG using standard CPB. The
      study population consisted of 325 patients who underwent coronary artery bypass
      grafting between June 2000 and December 2001 (mean age 60.02, range 38-83 years,
      242 males). Each patient had continuous ECG monitoring since the operation to the
      third postoperative day. AF occurred in 100 of 325 patients (30.76%). Patients
      were divided into two groups according to the presence (group A-100 patients) or
      absence (group B-100 patients) of post-CABG AF. Patients in both groups were
      compared. Intraoperative variables were used to compare the two groups. Patients
      with AF were significantly older (66.04 +/- 7.88 vs. 60.49 +/- 9.74 p = 0.0001).
      There was no statistically significant difference in the incidence of atrial
      fibrillation between the patients after coronary artery bypass grafting
      procedures, performed with or without cardiopulmonary bypass.

PMID- 16786749
TI  - [Systolic and diastolic left ventricle function assessment by tissue Doppler
      echocardiography in patients with perfusion defects in SPECT study].
AB  - INTRODUCTION: Tissue Doppler imaging (TDI) facilitates the quantitative
      assessment of the regional systolic and diastolic left ventricle function. Heart
      scintigraphy (SPECT) facilitates the assessment of regional perfusion of the
      myocardium. The aim of the study was the evaluation of the correlation between
      the regional myocardial perfusion defects observed in the SPECT study and the
      regional systolic and diastolic left ventricle function observed in TDI
      examination in the ischaemic heart disease patients. MATERIAL AND METHODS: In 40
      patients (33 men and 7 women) aged 43-74 years (mean age 56 years) diagnosed of
      ischaemic heart disease on the basis of coronary angiography, rest TDI
      examination was performed. Maximal systolic and maximal early-diastolic
      myocardial velocities were assessed in 13 myocardial segments of the left
      ventricle, supplied by respective coronary arteries (left anterior descending
      artery--LAD, circumflex artery--Cx, right coronary artery--RCA). During rest and
      exercise perfusion scintigraphy of the heart (Tc99 MIBI SPECT) myocardial
      perfusion was evaluated in the segments analysed previously during TDI study. On
      the basis of the SPECT examination results the patients were divided into three
      groups: group I) patients with fixed perfusion defects, group II) patients with
      exercise-induced perfusion defects and normal rest perfusion, group III) patients
      with normal perfusion during rest and exercise. RESULTS: Systolic and diastolic
      myocardial velocity in LAD and Cx supplied segments were significantly higher in
      group II and group III as compared with group I. Systolic and diastolic
      velocities of myocardium supplied by LAD were significantly lower in group II as
      compared with group III. In Cx supplied region the diastolic myocardial velocity
      was significantly lower in group II as compared with group Ill. CONCLUSIONS: In
      the left ventricle myocardial regions with fixed perfusion defects, statistically
      significant decrease of systolic and diastolic myocardial velocities was
      observed. Moreover, the decrease of diastolic myocardial velocity in the rest TDI
      examination was found in patients with normal rest perfusion and exercise-induced
      perfusion defects.

PMID- 16786750
TI  - [Intake of selected nutrients by perceived control over life, over health and
      general control in men and women aged 45-64, residents of Krakow].
AB  - The aim of this study was to compare mean intake of energy and selected nutrients
      in groups with high perceived control over life, over health, general control and
      the remaining part of population. The study sample was 3544 men and women aged 45
      4, residents of Krakow, randomly selected by sex, age and districts. Data on
      perceived control was collected by using 9-items questionaire. Nutrient intake
      was assessed by 24-hour recall. After adjustment to age and education, in men
      with high perceived control over life mean intake of witamin C was higher (56.3
      mg) than in the remaining men (49.0 mg). Compared with other women, women with
      high perceived control over health had lower mean intake of total energy (6403.9
      kJ vs 6831.9 kJ), proteins (56.3 g vs 60.1 g), carbohydrates (217.4 g vs 229.6
      g), fat (55.1 g vs 59.8 g) and sodium (1347.5 mg vs 1446.6 mg). In women with
      high general control, there was lower mean energy intake (6403.9 kJ vs 6773,9 kJ)
      and SFA intake (18.3 g vs 20.1 g) than in the remaining women. P/S ratio was
      higher in women with high general control (0.55) then in other women (0.49). In
      men with high general control mean intake of carbohydrates was lower (292.3 g vs
      310.3 g) then in the remaining men. There was no difference in nutrient intake in
      men with high perceived control over health and in women with high perceived
      control over life than in remaining part of the sample. In the study sample, high
      perceived control was related to more favourable diet in women, less effect was
      observed in men.

PMID- 16786751
TI  - [Homocysteine level, relationship with cardiovascular risk factors in selected
      Polish population].
AB  - The aim of the study was to evaluate the concentration and distribution of
      homocysteine in random samples of men and women aged 20-74 from two populations:
      urban (Warsaw) and industrial-rural (former Tarnobrzeg Province), and the
      estimation of relationship between selected cardiovascular risk factors and
      homocysteine concentration. In 2001 in 617 men and 657 women homocysteine level,
      lipids profile, glucose, folic acid, vitamin B12 concentration, blood pressure
      and alcohol intake were determined. The mean (geometric) homocysteine
      concentration was 10.9 micro mol/L in men and 9.6 micro mol/L in women. There
      were no differences in the homocysteine concentration and distribution between
      regions according to sex. The homocysteine level was connected with folic acid
      and vitamin B12 concentration in both genders. Moreover, in men was recorded
      relationship between homocysteine and body mass index, cholesterol level, alcohol
      intake, and in women between homocysteine and daily number of cigarettes smoked.

PMID- 16786752
TI  - [The assessment of quality of life after stroke, sex and age factors].
AB  - The aim of the work was quality of life depending on sex and age. The study
      included 79 persons, at age 25-70 after first stroke. Examination was provided in
      home conditions in 3, 6, 12 month after stroke. For evaluation of quality of life
      used was the London Handicap Scale questionnaire. In the present study quality of
      life people in the first year after stroke is increasing systematically. Women
      and younger people have higher adaptation skills for new life situation.
      CONCLUSION: quality of life is better in the second part of the first year after
      stroke.

PMID- 16786753
TI  - [Sociodemographic data and their influence on anxiety and depression in patients
      after spine surgery].
AB  - AIM: The aim of this study was to assess the score of HADS and the correlation
      with sociodemographic data in patients after spine surgery. MATERIAL: 40 patients
      after spine surgery because of low back pain and 20 persons of control group
      participated in the study. METHODS: HADS was used in the study. Socidemographic
      data were collected by means of Socio-demographic data questionnaire. RESULTS:
      Patients after spine surgery had worse results in HADS-A and HADS-D in comparison
      to control group. Men, older, worse-educated, unemployed, reporting more
      concomitant disease and medicine taking patients were more depressed. Anxiety
      correlated with age, education, tacking medicine and improvement after surgery.
      CONCLUSION: Patients after spine surgery need multidisciplinary care because of
      higher level of anxiety and depression.

PMID- 16786755
TI  - [Assessment of selected parameters measured on panoramic radiographs in
      postmenopausal women].
AB  - Osteoporosis and pathological bone fractures which are its consequences are a
      serious health problem of today's world. The aim of this study was to check if
      the picture of panoramic radiographs may contribute to early risk determination
      of this disease. The examination was carried out in women at the age 51-69. The
      group consisted of female patients, in whom, due to the lasting process of
      osteoporosis, the distal ephiphysis of radial bone was pathologically broken. The
      control group consisted of women who were volunteers and agreed to be examined.
      Density of bone tissue within the calcaneal bones was evaluated. In these female
      patients the panoramic radiographs were taken. The compacted substance of the
      base of mandible was assessed on both sides of the radigraph, distally from the
      mental foramen. Depending on the morphology of the compacted substance, the
      values of the MIC index were assigned to them. The value of PMI index was
      calculated. The results of the study were analysed statistically. Significant
      differences were indicated between parameters, which are derivatives of bone
      density and also statistically significant differences concerning the value of
      MIC index in both groups.

PMID- 16786754
TI  - [Changes in certain biochemical markers of bone turnover in rheumatoid arthritis
      patients treated with short-term low dose glucocorticosteroids].
AB  - Osteoporosis associated with rheumatoid arthritis (RA) is induced by chronic
      inflammation. Glucocorticosteriods (GCS) applied in the treatment of RA
      chronically reduce production of proinflammatory cytokines (IL-1, IL-6, and TNF)
      which are potent stimulators of bone resorption. On the other hand they directly
      reduce bone mass by inhibition of osteoblast. In order to assess bone turnover
      the following parameters have been measured: Alkaline phosphatase (AP), alkaline
      phosphatase-bone formation (AP-B), deoxypirydynoline (Dpd) and carboxyterminal
      telopeptides of type I collagen (CTx). Based on the obtained findings we conclude
      that: 1. Decrease in level of AP-B and CTx may suggest reduction of bone
      turnover, 2. Short-term low dose GCS therapy dramatically reduce inflammation
      which temporarily may reduce the loss of bone mass.

PMID- 16786756
TI  - [Sense of coherence in alcohol dependent males treated in departments of alcohol
      detoxication and rehabilitation--initial report].
AB  - The aim of this study was a comparison of the sense of coherence in the group of
      alcohol dependent male patients, with and without selecting psychosocial effects
      of alcoholism. The examined group consisted of 55 males treated in departments of
      alcohol detoxication and rehabilitation in Mental Hospital in Toszek. The SOC--29
      scale by Antonovsky was used in order to estimate the sense of coherence and
      specific questionnaire was used to show selecting psychosocial effects of
      alcoholism. SOC level was significantly higher in the group of men without
      psychosocial consequences of alcohol dependence.

PMID- 16786757
TI  - [Pressure ulcer prevention--evaluation of awarness in families of patients at
      risk].
AB  - Widespread use of risk assessing scales and standards in health care of
      chronically ill patients resulted in improvement of pressure ulcer prevention and
      treatment in institutional care. However many bed-ridden patients depend on
      awareness and preparation of families and caregivers, who provide home care after
      discharge from the hospital. The aim of this study was to evaluate the knowledge
      of pressure ulcers prevention in families of patient at risk. METHODS: During a 4
      month period, 62 caregivers (78% family members and 22% non-related) filled out
      the questionnaire enquiring about the issue related to pressure ulcer prevention
      and treatment. RESULTS: Only 11% of questioned person knew what the pressure
      ulcer was, 42% of caregivers were not aware of possible pressure ulcer causes,
      and 54.8% were not able to mention any pressure ulcer risk factor. Most of
      caregivers did not know basic principles of prevention including devices useful
      in pressure ulcer prevention, did not know about pressure reducing mattresses nor
      dressings used in pressure ulcers treatment. Fifty three percent of questioned
      persons never received any information about pressure ulcer prevention, and only
      23% received such information from nurses--which reflects low involvement of
      professional staff in education of families of patients at risk in principles of
      pressure ulcers prevention. CONCLUSIONS: Families and caregivers of bed-ridden
      patients have insufficient knowledge of pressure ulcer prevention. Contribution
      of medical staff in education of families of patients at risk in pressure ulcer
      prevention is minimal, indicating the need of preparation and implementation of
      an educational program for bed-ridden patients' caregivers.

PMID- 16786758
TI  - [Duodenal diverticula and choledocholithiasis in own material].
AB  - The detectability of duodenal diverticula (DD), a common duodenal pathology, has
      been growing with the increasing availability of endoscopic examinations, and
      especially of endoscopic retrograde cholangio-pancreatography (ERCP). The study
      is a retrospective analysis of incidence rates of DD and accompanying diseases of
      bile ducts, liver and pancreas detected by ERCP. We performed 8642 ERCP
      examinations between 1974 and 2001, which detected DD in 622 (7.2%) patients. Of
      these, 409 (65.8%) had choledocholithiasis, and 97 (15.6%) liver, gallbladder,
      bile ducts or pancreatic cancer. In the remaining 106 (17.0%) patients no
      pathologies requiring surgical intervention were found by radiological
      examination of bile ducts and pancreatic duct. In 10 (1.6%) patients with DD,
      caniulation of Vater papilla was not performed due to its anatomical location.
      Obtained results confirm relationship between DD and choledocholithiasis. It has
      not been established whether DD predispose to choledocholithiasis by interfering
      with bile duct emptying and causing bile lithogenicity, or rather that duodenal
      diverticula are caused by a concrement moved to duodenum by contractions of the
      gallbladder or sphincter of Oddi.

PMID- 16786759
TI  - [Studies on relationship between immunodeficiency in HIV-infected people and
      condition of upper gastrointestinal tract mucosa, prevalence of mycosis and
      Helicobacter pylori infection].
AB  - HIV infection leads to progressive deterioration of immunity. Upper
      gastrointestinal symptoms are often reported in patients with this infection. The
      aim of the study was to evaluate morphological changes in upper gastrointestinal
      tract mucosa and prevalence of opportunistic infections and Helicobacter pylori
      in HIV-infected people in relationship to the degree of immunosupression. We
      studied 94 HIV-infected patients with dyspeptic symptoms, 47 suffered from severe
      immunodeficiency expressed by low CD4+ lymphocyte count below 200/ mm3. Control
      group consisted of 52 non HIV-infected patients. During endoscopy,
      gastrointestinal tract mucosa was evaluated and biopsy samples were taken from
      gastric body and antrum for histopathological analysis and rapid urease test. In
      patients with CD4+ lymphocyte count below 200/mm3, endoscopic examination
      revealed significantly more frequent esophageal candidiasis (36%); whereas reflux
      esophagitis (13%) was significantly less often diagnosed in comparison to the
      rest of the patients. Duodenitis and duodenal erosions were also less frequent in
      them. Prevalence of Helicobacter pylori infection in gastric antrum was
      significantly lower in HIV-infected patients with severe immunodeficiency (40%)
      in comparison to the rest of the patients (72%) and control group (69%). Chronic
      active gastritis of the antral mucosa was less frequent in HIV-infected patients
      with CD4+ lymphocyte count below 200/mm3.

PMID- 16786761
TI  - [Prevalence of hepatitis C virus infection among haematological and oncological
      patients treated with blood products].
AB  - The aim of our study was to determine prevalence of hepatitis C virus infection
      (HCV) among patients with haematological and oncological diseases treated in the
      past with blood or blood products (about 20% among adults and about 50% in
      children in selected wards in 1992). Infection with HCV was detected in 3 out of
      64 examined patients (4.7%) and in 64 of 14 098 blood donors (0.4%), p < 0.05.
      The two HCV cases in the study group were in persons with haemophilia A treated
      with cryoprecipitate before 1992. Among 51 persons receiving transfusions only
      after 1992--1 case of HCV infection was detected (2.0%) Our results indicate
      improvement in the safety of treatment with blood and/or blood products and
      suggest that the present risk of HCV infection among patients with haematological
      and oncological diseases treated with these products after 1992 is rather small.

PMID- 16786760
TI  - [Sustained virological response in children with chronic hepatitis C treated with
      interferon alpha and ribavirin].
AB  - The aim of the study was to assess the effect of IFN-alpha and ribavirine
      combined therapy of chronic hepatitis C in children. The study comprised 37
      children (22 boys and 15 girls) aged between 4 and 18 years (mean 12 years and 6
      months) with chronic hepatitis C, diagnosed on the basis of serological,
      virological and histological criteria. The treatment included Intron A (Schering
      Plough) administered subcutaneously 3 M.U. 3 times a week and ribavirin (Rebetol
      Schering Plough) orally 15 mg/kg body weight daily for the period of 12 months.
      In all children liver biopsy was performed before the beginning of treatment.
      Tests for the presence of HCV RNA in serum were performed after 12-weeks therapy
      (EVR), after 6-months therapy, immediately on its completion (ETR) and 6 months
      afterwards (SVR), after the end of treatment. In the course of applied treatment,
      ALT activity, hemoglobin levels, leukocyte and trombocyte counts in the
      peripheral blood were determined every 4 week. EVR was obtained in 25 children
      and in these chidren genetic material of HCV in serum of blood was not observed
      both, after 6-months therapy, as well after the end of treatment. In this group a
      sustained virological response (SVR) was observed in 21 children. In 12 children
      without EVR, the elimination of HCV RNA was not achieved in the course of further
      treatment. CONCLUSIONS: 1. Twelve-months of combined IFN-alpha and ribavirine
      therapy enables to obtain a sustained virological response in about 56% of the
      treated children. 2. The frequency of recurrences of HCV infection in children
      amounts to 16%. 3. During the combined IFN-alpha and ribavirine treatment
      numerous side effects were observed, which in individual cases were the reason
      for treatment modification.

PMID- 16786762
TI  - [Genetic polymorphism and outcome in acute lymphoblastic leukaemia of childhood].
AB  - Current treatment strategies of leukaemia use risk factors existing at the time
      of diagnosis to establish risk-adapted therapy. This approach currently results
      in overall 95% rate of complete remission in paediatric acute lymphoblastic
      leukemia (ALL). However, as many as 30% of patients suffer from relapse and
      majority of children with ALL is profoundly affected by toxicity of anticancer
      drugs. In our study the probability of event free survival in children presenting
      with normal blast karyotype and treated according to BFM 90 protocol was 75%.
      This suggests the existence of factors independent from leukaemia genetic
      background, which influences the outcome of patients with ALL. This review is
      focused on genetic and functional polymorphism of enzymes that have or may have
      the influence on metabolism of drugs included in treatment protocol for ALL in
      children. Basic enzymes of anticancer drug metabolic pathways are described and
      frequency of their polymorphisms in Caucasian population is discussed.

PMID- 16786763
TI  - [The role of genetic polymorphisms within tumor necrosis factor promoter gene in
      non-Hodgkin's lymphomas].
AB  - Elevated tumor necrosis factor (TNF) and its soluble receptors (p55 and p75)
      plasma levels in patients with non-Hodgkin's lymphoma (NHL) have been shown to
      correlate with various adverse prognostic factors and predict poor NHL outcome.
      In vitro studies demonstrated that TNF expression level could be influenced by
      TNF-376, -308, -238, -163 promoters' polymorphisms. To explore whether these
      polymorphisms confer the susceptibility to and influence NHL outcome, we
      genotyped the TNF-376, -308, -238, -163 polymorphisms in 204 NHL patients and 96
      healthy controls. The frequency and distribution of polymorphic alleles were
      similar in both studied groups. TNF-308A was the only polymorphic allele related
      to elevated TNF, p55, p75 plasma levels (p = 0.009, p = 0.03, p = 0.007,
      respectively), lower complete remission rate (p = 0.01), higher progression (p =
      0.06) and death (p = 0.01) incidences. TNF-308A was the sole allele of
      independent prognostic significance for shorter freedom from progression (FFP)
      and overall survival (OS) (p = 0.009 and p = 0.017, respectively). These data
      indicate that innate immunity as reflected by the genetic propensity of the host
      to regulate TNF expression influences clinical course and outcome of NHL.

PMID- 16786764
TI  - [The role of HLA DRB1 genetic polymorphisms in non-Hodgkin's lymphomas].
AB  - The role of tumor necrosis factor (TNF)-308A polymorphic allele on non-Hodgkin's
      lymphoma (NHL) outcome was documented in the previous studies, although the role
      of the neighboring polymorphisms was unknown. The aim of the present study was to
      asses the frequencies and distributions of the HLA DRB1, TNF-308 and lymphotoxin
      alpha (LTalpha)+252 allelic polymorphisms in NHL patients and healthy controls
      and their influence on NHL outcome. The HLA DRB1, TNF-308 and LTalpha +252
      allelic frequencies and distributions didn't differ significantly between
      patients and healthy controls, thus it is unlikely that polymorphisms within the
      above mentioned sites confer susceptibility for lymphoma occurrence. Among the
      polymorphic alleles HLA DRB1*03, TNF-308A and LTalpha +252A remaining in linkage
      disequilibrium, TNF-308A was the only allele associated with higher TNF and its
      p55 and p75 receptors' plasma levels (p = 0.009, p = 0.03, and p = 0.007), lower
      complete remission rates (p = .006), shorter freedom from progression (FFP) and
      overall survival (OS) (p = 0.009 and p = 0.017, respectively). Among the
      polymorphic HLA DRB1 alleles, null HLA DRB1*02 was the sole allele along with the
      TNF-308A that remained independent factors for shorter FFP (relative risk [RR] =
      1.18, p < 0.02 and RR = 1.63, p < 0.0001, respectively) and OS (RR = 1.25, p <
      0.0001 and RR = 1.51, p < 0.0001, respectively). Innate immunity reflected by
      inherited HLA DRB1 genes repertoire and genetic propensity of the host to
      regulate TNF production and/or other closely linked genes influences clinical
      course and outcome of NHL.

PMID- 16786765
TI  - [Influence of selected clinical features on detection of sentinel node in
      patients with skin melanoma].
AB  - BACKGROUND: Combined use of preoperative lymphoscintigraphy, intraoperative
      detection of gamma radiation and intraoperative blue-dye staining allow for
      identification of sentinel node in 94%-100% of skin melanoma patients.
      OBJECTIVES: To assess the influence of clinical factors on the progress of
      preoperative lympho-scintigraphy, intraoperative detection of gamma radiation and
      intraoperative blue-dye staining, during sentinel node biopsy procedure in skin
      melanoma patients. MATERIAL AND METHODS: From 1.12.1999 to 30.06.2001 in
      Department of Surgical Oncology, Medical University of Lodz, in 74 patients with
      skin melanoma, sentinel node biopsy was performed. Analysis comprised the
      influence of: age, sex, skin complexion of patients, diameter of primary tumor,
      presence of ulceration in primary tumor and location of primary tumor, on
      progress of parts of sentinel node biopsy. RESULTS: In subgroup of patients in
      whom time of sentinel node identification during preoperative lympho-scintigraphy
      was longer than 10 minutes, statistically significant relationship was found
      between time of identification and location of primary tumor (p < 0.05). The time
      was shortest in patients with primary tumor located on lower extremity and was
      the longest in patients with primary tumor located on head and neck.
      Statistically significant correlation was found between skin complexion and
      degree of sentinel node staining. In all red haired patients with light skin
      complexion full staining of sentinel node was observed. In patients with dark
      skin complexion full staining of sentinel node was observed only in 61.5% of
      cases. There was no statistical relationship between remaining clinical features
      and progress of preoperative lympho-scintigraphy, intraoperative detection of
      gamma radiation and intraoperative blue-dye staining. CONCLUSIONS: The time of
      identification of sentinel node during preoperative lympho-scintigraphy is
      related to location of primary tumor. The progress of intraoperative detection of
      gamma radiation is not related to studied clinical features. Degree of sentinel
      node staining is related to skin complexion of patient.

PMID- 16786766
TI  - [Evaluation of tolerance and efficacy of postoperative combined radiotherapy and
      chemotherapy in locally advanced gastric cancer].
AB  - PURPOSE: To assess the toxicity and the efficacy of adjuvant radio-chemotherapy
      in patients with high-risk gastric cancer. METHODS AND MATERIALS: Patients with
      adenocarcinoma of the stomach were enrolled into the study from April 1999 to
      December 2000. There were 15 females and 27 males, 33 to 69 years old (median
      52). There were following inclusion criteria: tumor stages T1-2 N1-3 or T3-4 N0
      3, no distant metastases (except resected metastases to sac or spleen). All
      patients had lymph node and/or serosal involvement. Radiation dose of 42.5 Gy in
      1.7 Gy per fraction was delivered to the tumor bed and regional lymph nodes over
      5 weeks. In 4 cases of nonradical surgery a boost dose of 8.5 Gy was given.
      Chemotherapy consisted of 5-Fu 325 mg/m2/day, given on day 1-3 and 29-31 of
      radiotherapy. RESULTS: All patients completed radiotherapy as planned. Mild
      nausea/vomiting in 43% of pts., leucopenia WHO 1 and 2 in 43% of pts. as well as
      WHO 3 in 5% of pts. and diarrhea WHO 1 and 2 in 21% of pts. were the most
      frequent toxicities. Three year relapse-free survival and overall survival rates
      were 29% and 31%, respectively (median 12 and 18 months). Three year survival
      rates in stage II, III and IV were 67%, 24% and 17% respectively. CONCLUSION:
      Postoperative radio-chemotherapy in patients with locally advanced gastric cancer
      was safe and well tolerated. The results obtained in this study and from
      literature suggest that adjuvant radio-chemotherapy may improve 3-year survival
      rates by 10-15% compared to historical controls treated with surgery alone.

PMID- 16786767
TI  - [Cryotherapy of liver tumors].
AB  - AIM OF THE STUDY: To assess the value of cryodestruction during cytoreduction of
      liver tumors in the patients undergoing palliative treatment as well as
      evaluation of the frequency and type of complications of the method. PATIENTS AND
      METHOD: Between 1990-2001, 33 cryodestruction of maligant tumors of liver were
      performed for primary tumor in 8 cases and for metastatic lesions in 25. Thirteen
      patients had single, and the remaining 20 multiple lesions in liver. In 11 cases
      cryotherapy supplemented resective procedures or devascularisation of liver
      parenchyma. RESULTS: Mean time of follow-up was 14 months in the patients
      subjected to cryotherapy alone and 10 months in those subjected to cryotherapy as
      a supplementing modality. Postroperative complications related to cryotherapy did
      not exceed 9%, and overall mortality was 3%. CONCLUSIONS: Cryoablation is
      valuable alternative for other methods of palliative treatment in the patients
      with liver tumors.

PMID- 16786768
TI  - [Age as a prognostic factor in colorectal cancer treatment].
AB  - Aging of the population leads to increasing the numbers of patients requiring
      surgical interventions. Though highest incidence of colorectal cancer occurs in
      the age range between 60-70 years, the incidence of colorectal cancer in the age
      group below 40 years has been also increasing. In this age group the course of
      the disease and prognosis are different than in the patients over 60 years of
      age. The authors are analysing data from the study protocols of 1332 patients
      operated for colorectal cancer at our Department of Surgery between 1984-2000.
      The results obtained in 3 age groups were compared: group I--patients < or = 40
      years (n = 56), group II patients between 41-70 years (n = 944), group III > 70
      years (n = 332). No significant differences related to the stage of the disease
      and the number of asymptomatic patients were observed between groups. The
      patients below 40 years had more lesions of multiple type, and the number of
      emergency procedures was lower. The number of resective procedures was the
      highest in this group similarly as the rates of recurrent disease, either local
      or systemic. The patterns of five-year survival in the age group below 40 years
      and over 70 were similar. Colorectal cancer in the patients below 40 years of age
      has poor prognosis, however long-term survivals are similar as in the patients
      over 70 years. Due to the lack of concomitant diseases in the patients with
      colorectal cancer below 40 years, prognosis in this group is the worst.

PMID- 16786770
TI  - [Prognostic value of low hemoglobin concentration in adjuvant radiotherapy after
      total laryngectomy in group of patients with laryngeal cancer].
AB  - PURPOSE: To investigate the impact of hemoglobin concentration (Hb) at the start
      and end of radiotherapy, and the drop of hemoglobin concentration during
      radiotherapy on the loco-regional control in postoperative radiotherapy for
      patients with advanced laryngeal cancer. MATERIALS AND METHODS: Between January
      1993 and December 1996, 254 patients with pT3 or pT4 and pN0-pN2 laryngeal cancer
      were treated with a total laryngectomy and adjuvant radiotherapy (RT). The median
      age of patients was 56.3 years (range: 30-70 years). The analyzed group consisted
      of 236 males (92%) and 18 females (8%). In all cases a total laryngectomy was
      performed. 196 out of 254 patients underwent homolateral neck dissection and 58
      out of 254 underwent bilateral neck dissection. The primary tumor bed was
      irradiated to the median total dose of 61.2 Gy (range: 57 - 64 Gy) and all
      regional lymph nodes were treated in all patients to a dose of 50 Gy. Indications
      for postoperative RT were close postoperative margins at the tumor site or
      pathological status of lymph nodes described as pN1 or pN2. Univariate analyses
      were used to determine the predictors for locoregional failure. The following
      factors were studied for prognostic importance of loco-regional outcome: the
      hemoglobim concentration at the start of radiotherapy, at the end of
      radiotherapy, and the drop of hemoglobin concentration during radiotherapy, age,
      sex, pT and pN categories. RESULTS: The actuarial 5-year overall survival was
      49%, the actuarial loco-regional control rate was 70%. Univariate analysis, using
      log-rank test indicated that pN +, Hb level at the end of RT (p = 0.004) and drop
      during RT (p = 0.038) were predicted for the loco-regional control of
      postoperative radiotherapy. CONCLUSIONS: Analysis showed that the low level of Hb
      at the end of radiotherapy and the drop during radiotherapy were correlated with
      decreasing of the loco-regional control of adjuvant radiotherapy for patients
      with advanced laryngeal cancer.

PMID- 16786769
TI  - [Prognostic factors in patients with cervical--confined endometrial carcinoma
      treated with surgery and postoperative radiotherapy].
AB  - OBJECTIVE: The aim of the study was to determine prognostic factors in the group
      of the patients with uterine--confined endometrial carcinoma treated with surgery
      and postoperative radiotherapy. MATERIAL AND METHODS: The authors analyzed 102
      patients (mean age 58 years) with stage 1 (74 patients) and stage 11 (28
      patients) endometrial carcinoma. All patients were treated with surgery
      (abdominal hysterectomy and bilateral adnexectomy) and postoperative
      radiotherapy: external beam pelvic irradiation (20 patients), vaginal cuff
      irradiation (33 patients) and combination (49 patients). Analysed were prognostic
      factors as follows: age, stage, tumor grade, depth of myometrial invasion,
      hormone receptors, expression of the tumor suppressor gene p53, Her 2/neu and MIB
      1 (ki-67 paraffin). RESULTS: In our group of patients, multivariate analysis has
      identified tumor grade, progesterone receptors status and MIB-1 as independent
      significant prognostic factors.

PMID- 16786771
TI  - [Myocardial dysfunction, neuropathy and nephropathy in long standing type 1
      diabetic patients].
AB  - Cardiovascular and renal complications among type 1 diabetic patients are
      predictive factors for sudden cardiac death and stroke. The aim of the study was
      to assess the prevalence of diabetic nephropathy and autonomic neuropathy in type
      1 diabetic patients with and without diastolic dysfunction in echocardiographic
      examination. The study was performed in a group consisting of 37 patients with
      type 1 diabetes mellitus. Mean age of the study group equaled 37.24 +/- 10.85
      years, duration of diabetes mellitus 21.3 +/- 9.55 years. All patients performed
      EKG, and cardiovascular autonomic test with ProSciCard according to Ewing
      battery. The following parameters were assessed: heart rate (HR), standard
      deviation of HR, RMSDD, VLF, LF, HF, deep breathing test, Ewing supine test and
      Valsalva maneuver. Systolic and diastolic function was assessed in
      echocardiography examination at rest. In all patients following laboratory
      parameters were assessed: HbA1c, total chol, LDL-chol, HDL-chol, triglicerides,
      uremic acid, glucose, albumin, creatinine, cystatin C, microalbuminuria. RESULTS:
      mean heart rate in the examined group --78.38 +/- 15.54 /min, VLF--1.59 +/- 1.7;
      LF--4.22 +/- 1.51, HF--0.82 +/- 0.88, mean heart rate during deep breathing test 
      -79.63 +/- 13.71, Ewing ratio--0.91 +/- 0.11. Cardiovascular autonomic neuropathy
      and diabetic neuropathy were diagnosed in 3 patients, these patients suffered
      also from proliferative retinopathy and diabetic nephropathy. The remaining group
      of 34 patients has normoalbuminuria. Calculated creatinine clearance according to
      Cockroft-Gault equation was 88.85 +/- 9.60 m/min, cystatin C concentration--0.97
      +/- 0.22 ng/ml. In echocardiography exam, there were no abnormalities in systolic
      function, and diastolic dysfunction was diagnosed in 15 patients. Preliminary
      results showed that only the cystatin C level significantly differed patients
      with and without diastolic dysfunction in echocardiographic examination. Cystatin
      C could be the first sign of renal failure among these patients. Cardiovascular
      autonomic neuropathy and diabetic nephropathy were diagnosed only in 3 patients
      with left ventricular diastolic dysfunction in echocardiographic study.

PMID- 16786772
TI  - [Radiotherapy combined with hormonal therapy as treatment method in patients with
      prostate cancer: still more questions than answers].
AB  - Treatment of prostate cancer is a challenge for both urologists and radiation
      oncologists. Currently two radical methods of treatment are recommended i.e.
      radical prostatectomy and radiotherapy. Hormonal therapy is mainly indicated for
      treatment of patients with metastases, but lately has become popular in
      combination with radical radiotherapy. Outcome of radiotherapy in more advanced
      stage of disease due to high risk of distant metastases and local failure is
      unsatisfactory. In the last years the introduction of combined treatment
      consisted of radiotherapy and hormonal therapy may lead to improvement of results
      of treatment. The general rationales for combining radiotherapy and hormonal
      therapy are fourfold: decreasing prostate volume, diminishing of amount of cancer
      cells, improving tumor oxygenation, and elimination of micro metastasis. One of
      the first trials, which indicated that combined treatment might improve results
      of treatment, was RTOG 8307. In this trial two strategies of hormonal therapy
      were compared: megestrol acetate versus diethylostilbestrol. The comparison of
      results from this trial to historical study control group indicated that combined
      treatment gave benefit. Another trial, which indicated that combined treatment
      might produce better results, was RTOG 8531. Results from this trial indicated
      that better local control is achieved by combined treatment. Another trial, which
      indicated benefit due to implementation of hormonal therapy to radiotherapy, was
      trial RTOG 8610 The EORTC 22863 reported an improvement in the estimated 5-year
      overall survival (79% vs. 63%). In investigational trial hormonal therapy after
      radiotherapy ending was continued for three years. The RTOG 9202 was the latest
      study, which indicated benefits obtained by long lasting adjuvant hormonal
      treatment. This study showed that 2 years of adjuvant hormonal therapy produced
      significant prolongation of the 5-year overall survival by 80% in comparison to
      69% for patients treated without adjuvant hormonal therapy. Despite these few
      trials, lacking is still data and the following crucial questions are waiting for
      answers in the near future: What is the optimal timing of hormonal therapy? Which
      patients will obtain the greatest benefits due to combined strategy? How does
      long lasting hormonal therapy influence on patient's quality of life? Future
      trials (RTOG 9413 and RTOG 9901) will give some answers to the mentioned above
      questions. Currently we can conclude that in the group of patients with high risk
      of relapse, hormonal therapy with radiotherapy improve results of treatment.

PMID- 16786773
TI  - [Adjuncts to surgery in cervical cancer].
AB  - Beside radiotherapy, radical hysterectomy with pelvic lymph node dissection is
      the cornerstone of early cervical cancer management. Surgery allows for more
      accurate evaluation of tumor extension as compared to non-invasive procedures
      preceding definite radiotherapy. Treatment failures after surgery include local
      regional recurrences and distant metastases, and their proportion varies in
      particular series. In this study, we address the risk factors for recurrence in
      early-stage cervical cancer patients managed with primary surgery: lymph node
      positivity, deep stromal invasion, lymphovascular space involvement and
      positivity of surgical margins. Based on both retrospective and randomized
      studies, currently two adjuncts to surgery: radiotherapy and chemotherapy, used
      alone or in combination are employed. The indications for these approaches are
      reviewed. Additionally, the recommendations of American Brachytherapy Society for
      the use of postoperative brachytherapy are presented.

PMID- 16786774
TI  - [The influence of trauma on immunological response (the role of Tgammadelta+
      lymphocytes)].
AB  - The influence of trauma, especially surgical operation on immunological response
      has not been clarified sufficiently. The authors discuss the influence of
      surgical trauma on humoral and cell mediated immune response and on phagocytosis
      as well. The role of Tgammadelta+ lymphocytes in immunological processes that
      occur after trauma have been also discussed.

PMID- 16786775
TI  - [Premenstrual syndrome--current approach].
AB  - Premenstrual syndrome (PMS) affects 3-5% of women. It still remains controversial
      in diagnosis and treatment. Dynamic progress in neuroendocrinology in recent
      years led to PMS etiology explanation. It also influenced therapeutic approach.
      According to Wang et al. neuroactive steroids and their imbalance evoke PMS
      symptoms. That theory introduced other therapeutic interventions restoring
      neuroendorine balance. The newer antidepresants demonstrated excellent efficacy
      in treatment of somatic and emotional PMS symptoms. PMS is a typical object of
      contemporary studies on therapeutic efficacy according to evidence based
      medicine.

PMID- 16786776
TI  - [Interstitial lung disease related to systemic connective tissue diseases].
AB  - Interstitial lung disease (ILD) is one of the most frequent and most serious
      complications of connective tissue diseases such as systemic sclerosis, systemic
      lupus erythematosus, dermato- and polymyositis, Sjogren's syndrome, or mixed
      connective tissue disease. Diagnosis of ILD is often delayed in patients with
      connective tissue diseases because of the systemic character of the primary
      condition, restricted physical activity of the patient and insufficient awareness
      of the physycian. The aim of the current review is to present the up-to-date
      information on ethiopathology, classification, diagnosis and treatment of ILD in
      patients with connective tissue diseases.

PMID- 16786777
TI  - [Allergia rhinosinusitis. Diagnosis, programming and treatment monitoring].
AB  - Allergic rhinitis (AR) is one of the most common airway diseases. About 15% of
      population suffers from this disease and the prevalence of this illness is still
      increasing. The symptoms of AR (itching, sneezing, watery nasal discharge) may be
      persistent or intermittent. Persistent AR often leads to sinusitis (in about 50%
      of patients), to bronchial asthma (in 40-50% of cases), to conjunctivitis (in >
      40%) and to nasal polyps (in 10-15%). The main reasons for AR symptoms are
      environmental allergens (mites, pollen grains, moulds, animal epithelia) as well
      as foods, some drugs and chemicals. Diagnosis of AR is based on history,
      rhinoscopy, cytology of nasal smear. In IgE related AR very important are
      positive skin prick tests with allergens and the increase of allergen specific
      IgE in serum. In the treatment of AR most important are: allergen avoidance,
      topical antihistamins and steroids. Sometimes topical anticholinergics and nasal
      decongestants are used. In severe symptoms oral antihistamines and oral steroids
      are needed. In some cases of IgE related AR specific immunotherapy is applied.

PMID- 16786778
TI  - [Contact urticaria syndrome].
AB  - Current point of view on patho-mechanism, diagnosis, clinical features and
      prevention of contact urticaria syndrome was presented, especially with emphasis
      on systemic symptoms existing in this disease. The importance of allergic and non
      allergic reaction in pathogenesis of this syndrome was also discussed. Special
      attention was paid to possibility of life threatening symptoms appearing during
      the contact of allergens or other physical agents with the skin. In addition the
      principles of prophylaxis in such cases were described.

PMID- 16786779
TI  - [Eosinophil in allergic and non-allergic inflammation].
AB  - Eosinophiles are the cells, which play a crucial role in different pathological
      events. The atopic and parasitic disorders, as well as hipereosinophilic syndrome
      (HES) are the most typical processes in which they take part. Eosinophilia, which
      is the rise of number of eosinophiles in peripheral blood above 500 in 1 microl,
      or above 5% in smear of leucocytes can exist both in allergic and infectious
      diseases, as well as in neoplasmic and autoimmunological disorders, and in
      reactions to drugs or others. The mechanism of activation of eosinophiles in
      atopic diseases is well known and is connected with IL-5, IL-4 and IL-13.
      According to the last literature data, three routes of activation of eosinophil
      can be distinguished: Th2 route connected with cytokines: IL-5, IL-4 and IL-13,
      Th1 route connected with cytokines: IFN-gamma 11-12, GM-CSF, as well as internal
      route connected with IL-1, TNF, GM-CSF. The experience of different routes of
      eosinophil's activation may be helpful in the differential diagnosis of
      eosinophilia.

PMID- 16786780
TI  - [Bronchial challenges in asthma diagnosis].
AB  - The evaluation of bronchial hyperreactivity is useful for diagnosis atypical form
      asthma, in monitoring of anti-inflammatory treatment, in epidemiology and in
      scientific research. Different stimuli indirect and direct are applied to asses
      bronchial reactivity. Direct stimuli e.g. methacholine and histamine cause airway
      limitation by acting on airway smooth muscle. By contrast indirect stimuli
      (exercise, nonisotonic aerosols, adenosine, mannitol) cause airway limitation by
      acting inflammatory cells and neuronal cells which release mediators to cause
      secondary broncho-constriction. Bronchial challenges with direct stimuli are less
      sensitivity but more specific than the direct challenges in differentiating
      asthma from normal.

PMID- 16786781
TI  - [The importance of regulation of endogenous methylarginine concentrations in
      clinical practice].
AB  - Endogenous methylarginines, the catabolism products of proteins containing post
      translationally methylated arginine residues, are the modulators of arginine
      metabolism. Endogenous methylarginines compete with arginine about cationic
      aminoacid transporter and some of them, e.g. asymmetric dimethylarginine (ADMA)
      and N-mono-methylarginine (MMA), are competitive inhibitors of nitric oxide
      synthases. The changes of arginine metabolism, induced by these methylarginines,
      may have serious consequences, because arginine is the precursor of cell
      signalling molecules such as NO, agmatine, glutamate and gamma-aminobutyric acid
      (GABA) and the regulatory molecules polyamines. ADMA has also prooxidant
      properties and increases endothelial adhesiveness for monocytes. Asymmetric
      methyl-arginines induce endothelial dysfunction, which may be reversed by L
      arginine supplementation, what is defined as "arginine paradox". The increased
      plasma concentration of asymmetric methylarginines is induced by
      hypercholesterolemic or hyperhomocysteinemic diets and by rich sodium chloride
      intake. The high level of plasma asymmetric methyl-arginines accompanies
      atherosclerosis, hypertension, chronic renal failure, diabetes, insulin
      resistence, hyperthyreosis, schizophrenia and sclerosis multiplex. The causes of
      increased concentration ADMA and MMA in these diseases are just now discovered.
      The hope in the future is the modulation of methylarginines concentration by
      regulation of expression and activities of enzymes taking part in the metabolism
      of these substances, particularly of dimethyl-arginine dimethyl-aminotransferase.
      The main aim of the present study is to pay attention to possibility of the
      modulation of asymmetric methyl-arginines concentration, what may be a new way of
      synthase nitric oxide activity regulation in vivo and may be useful in future
      therapy of patologies in which synthesis of NO is troubled.

PMID- 16786783
TI  - [Atherosclerosis and rheumatoid arthritis].
AB  - There is growing evidence that patients with rheumatoid arthritis (RA) are at
      higher risk of cardiovascular diseases (CVD) including myocardial infarction and
      stroke. Recent analysis indicate that CVD is the most common cause of death in
      RA; however research on traditional risk factors such as smoking, hypertension or
      elevated cholesterol level has shown mixed results. There are many convincing
      suggestions that RA-specific factors associated with systemic inflammation may
      play a critical role in endothelial cell damage and accelerated development of
      atherosclerosis. Since atherosclerosis is currently recognized as a chronic
      inflammatory condition that can be converted into an acute clinical event by
      plaque rupture and thrombosis--the interplay between inflammatory mediators
      including cytokines (TNF-alpha, IL-1, IL-6), C-reactive protein, blood
      coagulation factors and vessel wall cells attracts much attention. Their pivotal
      role in the pathogenesis of both diseases, RA and atherosclerosis has been
      presented and discussed in our review.

PMID- 16786782
TI  - [Heart surgery in patients with chronic renal insufficiency: risk factors,
      outcome, management].
AB  - Cardiovascular diseases are one of the most common causes of hospitalization.
      Renal failure is a very important risk factor in patients undergoing heart
      surgery. So far few authors have written about non-dialysis dependent patients
      with mild renal insufficiency undergoing heart surgery. The purpose of this study
      is to present most important risk factors and outcomes in patients with different
      stages of renal insufficiency. The authors have studied attentively non-dialysis
      dependent patients with mild renal insufficiency because of high risk of
      pooperative renal failure in this population. To diminish high risk of
      perioperative death in these patients, there is a need for very close co
      operation between cardiologists, cardiac surgeons and nephrologists.

PMID- 16786784
TI  - [Risk factors and early prevention of osteoporosis].
AB  - Osteoporosis is a generalized bone disease that is characteristed by diminish of
      bone mass and destruction of bone microarchitecture, which leads to increased
      risk of bone fractures. The appearance of disease to much extent depends on the
      amount of bone mass that has been stored in the periods of childhood and
      adolescence. This article discusses basic factors which determine correct bone
      building including genetic, hormonal and environmental factors. The awareness of
      their existence as well as the knowledge of risk factors allows to implement
      proper, early prevention of this disease becoming more and more common.

PMID- 16786785
TI  - [Auditory neuropathy--new disease].
AB  - Auditory neuropathy, a disorder of neural synchrony, is a retrocochlear hearing
      disorder identified by absence of auditory brainstem responses (ABR) and presence
      of evoked acoustic otoemissions (EOA). Registration of emissions shows normal
      function of external cilliary cells. Patients with auditory neuropathy have
      difficulties to understand speech especially in presence of beckground noise.
      Normal conversation requires the support of orofacial reading. The authors
      presents electrophysiological and behavioral tests useful in diagnostic process.
      An option in treatment of auditory neuropathy is cochlear implantation. Such
      treatment is indicated when conventional hearing aids doe not help to improve
      speech understanding.

PMID- 16786786
TI  - [Postoperative nausea and vomiting (PONV)--causes, prevention, treatement].
AB  - The paper approximates news relating to pathophysiology, prophylaxis and
      treatment of postoperative nausea and vomiting, which, besides the pain, remain
      some of the most unpleasant memories of the recovery phase. In spite of the fact
      that they belong to very common ailments of the postoperative phase, they are
      placed low on this list, probably because the common belief that they do not
      threaten life imminently. However they may cause a varity of undesired symptoms,
      among them aspiration of stomach contents into the lungs in patients with
      impaired consciousnesess, also dehydratation, and electrolytic disturbances,
      especially with children and older patients. This paper has presented methods for
      their prevention and treatment.

PMID- 16786787
TI  - [Psychosocial consequences of genetic susceptibility on development of disease].
AB  - The development of predictive genetic DNA- tests gives people the choice "to
      know" or "not to know" a decision with tremendous short-mid- and long-term
      consequences. Family history of disease can provide information about the
      increased risk of susceptibility, and these knowledge may have psychosocial
      implication. The results of studies using genetic testing and their psychological
      impact are discussed with regard to hereditary cancer (breast, colorectal,
      prostate) as well as particular neurogenetic disease (e.g. Huntington' disease).
      Psychological studies on genetic risk concentrating on psychological adjustment,
      transfer of information within the family and perception of genetic risk in
      families showed that genetic disease had a considerable impact on family life
      (e.g. reproductive decisions). Findings showed that people with a family history
      of cancer (without genetic testing) vary in their illness behaviour, but little
      is known about the effect of inheredited predisposition to disease (e.g. cancer)
      on such health related behaviour as smoking, diet, activity level. Genetic
      information could both increase (strengthening the belief that current behaviour
      combined with genetic predisposition is putting person at increasing risk of
      disease) and decrease motivation to change behaviour (weakening belief that
      changing behaviour will reduce risk of disease because genetic is immutable).

PMID- 16786788
TI  - [Animal transgenesis for necessities of xenotransplantation].
AB  - The presence in humans of xenoreactive antibodies directed against swine Gal
      antigen present on the surface of xenograft donor cells, leads to the complement
      activation and immediate xenograft rejection--as a consequence of hyperacute
      immunological reaction. The graft of genetically modified organ of a swine
      depleted of at alpha1,3-galactosylotransferase enzyme that is responsible for Gal
      antigen origin, would be tolerated with simultaneous administration of medicines
      decreasing other less severe immunological reactions. To prevent hyperacute
      rejection it is also possible to modify swine genome by human genes controlling
      enzymatic cascade of complement or modifying the set of donor's cell surface
      proteins. The removal or significant reduction of number of Gal antigen molecules
      prevents complement activation. In this situation, the main reason for the graft
      rejection is malfunction of the regulation of coagulation system inside the graft
      and cellular reactions involving macrophages, neutrophiles, NK cells and
      lymphocytes T. Minor genetic differences between the acceptor's organism and the
      donor of grafting organ can lead to so called delayed xenograft rejection. As our
      knowledge about reactions taking place inside grafted tissue will increase it
      would be possible to introduce genes controlling coagulation system into swine
      genome.

PMID- 16786789
TI  - [Ehrlichiosis].
AB  - Ehrlichiosis is a disease caused by Ehrlichiae bacteria. The disease is
      transmitted by ticks. The disease occurs in the following clinical forms:
      monocytic ehrlichiosis, granulocytic ehrlichiosis and sennetsu fever. Symptoms of
      ehrlichiosis are non-specific, and include flu-like symptoms, cutaneous
      manifestations (erythema), enlargement of the lymphatic nodules, liver and
      spleen. Involvement of the gastrointestinal tract is common in the patients.
      Symptoms are accompanied by alteration seen in peripheral blood (leukopenia with
      lymphocytopenia, thrombocytopenia). Antibiotics are used in management of
      ehrlichiosis.

PMID- 16786790
TI  - [Amyloidosis in patients with rheumatoid arthritis].
AB  - Current views on the pathogenesis of reactive amyloidosis are presented.
      Diagnostic methods used, clinical picture, prognostic factors and methods of
      treatments are discussed.

PMID- 16786791
TI  - [Systemic sclerosis--clinical course and treatment possibilities].
AB  - Systemic sclerosis is an autoimmune disease, characterized by fibrosis of the
      skin and internal organs, such as esophagus, heart, lungs, and kidneys. Three
      main forms of systemic sclerosis are conspicuous: diffuse systemic sclerosis,
      limited systemic sclerosis and scleroderma sine sclerosis. Respective variants
      differ in skin sclerosis exacerbation, progress and prognosis; whereas organ
      involvement, osseous and articular alterations are comparable in all forms of the
      disease. Due to the fact that etiology of systemic sclerosis is not known, no
      specific therapy has been developed. The therapy is based on influencing main
      pathogenetic factors, such as peripheral circulation disturbances, abnormal
      immune activation and increase in collagen accumulation. An overview of clinical
      course of systemic sclerosis and new therapeutic modalities is provided.

PMID- 16786792
TI  - [Metabolic polymorphisms and biomarkers of exposition to polycyclic aromatic
      hydrocarbons (PAH)].
AB  - Polyunsaturated aromatic hydrocarbons (PAHs) are formed during the incomplete
      combustion of organic material, as an ingredient in cigarette smoke, in exhaust
      fumes, and forest fires. They are not electrophilic per se, but are converted to
      electrophiles by cellular enzyme systems. Enzymes with these function fall into
      classes "phase 1" and are members of cytochrome P450 superfamily of
      monooxygenases. Reactive hydrophilic intermediates of PAH bind convalently to DNA
      and form highly mutagenic DNA adducts. "Phase 2" conjugating enzymes such as
      glutathion-S-transferases (GS) act as inactivating enzymes. Polymorhisms of genes
      involved in metabolism of PAH and their influence on DNA adducts formation and
      cytogenetic biomarkers as a cancer suscetibility factors are presented.

PMID- 16786793
TI  - [Patient satisfaction as the main indicator of primary care quality].
AB  - Patient satisfaction is increasingly considered to be one of the most important
      factors in the measurement of quality of medical care. In the paper we show the
      most important aspects of patient satisfaction and the main reasons for its lack.
      We also suggest the possibilities of measurement and improvement of patient
      satisfaction as the main factor of better clinical care and a properly
      functioning family doctor.

PMID- 16786794
TI  - [Phototherapy in dermatology].
AB  - Treatment of some skin diseases by exposure to ultraviolet radiation is
      presented. Phototherapy including radiation of different lenghts of waves has
      been used in medicine for along period of time, it also plays an importaint role
      in modern dermatology. The study presents the modern methods of phototherapy and
      photochemiotherapy as well as history, indications, contraindications and side
      effects of phototherapy.

PMID- 16786795
TI  - [Thrombocytopenia as a complication of nonsteroidal anti-inflammatory drug
      treatment].
AB  - Thrombocytopenia can be a severe complication of nonsteroidal anti-inflammatory
      drug treatment. We report a case of a 58 year old patient who developed severe
      thrombocytopenia during treatment with ketoprofen. Within several days the
      platelet count decreased to undetectable values in routine blood count. In
      parallel, symptoms of severe hemorrhagic diathesis occurred. Immunoenzymatic
      tests and result of bone marrow trepanobiopsy ruled out underlying cancer and
      idiopathic thrombocytopenic purpura (antiplatelet antibodies were not detected).
      After discontinuation of ketoprofen and treatment with corticosteroids, the
      patient's platelet count returned to normal and remained stable at 6 months of
      follow-up.

PMID- 16786796
TI  - [A case of emphysema suggesting cystic lung disease in computer tomography].
AB  - Pulmonary emphysema is anatomically defined as abnormal persistent enlargement of
      the air spaces distal to the terminal bronchioles, accompanied by destruction of
      alveolar walls, without evident fibrosis. High-resolution computer tomography
      (HRCT) imaging is a valuable tool for diagnosis of this disease. The presence of
      minute cysts distributed evenly through all lung zones is rarely observed in
      pulmonary emphysema. In such cases, emphysema should be differentiated from other
      cystic lung diseases. We present a case of a 45-year-old women admitted to our
      Department with dyspnoea on exertion. Physical examination revealed no
      abnormalities. A chest radiograph showed diffused interstitial lesions in both
      lungs; HRCT revealed multiple oval-shaped cysts equally dispersed in all lung
      areas. The pulmonary function tests revealed increased lung volumes (total lung
      capacity 114.6% predicted, residual volume 200.6% of predicted), while both vital
      capacity and FEV1 were decreased (73.6% and 54.0% of predicted volumes,
      respectively). Diffused lung capacity was normal. Trans-bronchial biopsy was non
      contributory. Histiological examination of lung tissue obtained by videothoraco
      scopy (VTS) was diagnostic for bullous emphysema. The patient had prescribed
      ipratropium bromide and teophyline. Differential diagnosis, apart from pulmonary
      emphysema, should take into consideration lymphangioleiomyomatosis, histiocytosis
      and sarcoidosis.

PMID- 16786797
TI  - [Variant angina pectoris associated with Morgagni-Adams-Stokes syndrome--case
      report].
AB  - We report a case of Prinzmetal angina initially manifested with short losses of
      consciousness in a 55-year-old man hospitalized in the Department of Coronary
      Artery Disease, Institute of Cardiology, Jagiellonian University Medical College
      in Cracow. Clinical symptomatology of the presented case, causes and mechanism of
      loss of consciousness in variant angina as well as treatment methods are
      discussed.

PMID- 16786798
TI  - [Acute inferior and right ventricular myocardial infarction in a patient with
      congenital secundum atrial septal defect].
AB  - We are presenting the case of a forty-six-year old patient, with a previously
      undiagnosed congenital secundum atrial septal defect, admitted to the intensive
      care ward because of an acute inferior and right ventricular myocardial
      infarction. He was randomised to Gusto V Trial and intravenous therapy of
      reteplase and abciximab was administered, which resulted in electrocardiographic
      reperfusion. After several hours of right ventricular failure his condition
      improved. No complications were observed throughout the convalescence. During the
      routine TTE examination a secundum ASD was diagnosed and confirmed afterwards in
      the TEE examination. Patient was qualified for coronarography which revealed a
      critical lesion in the right coronary artery; successful PCI was conducted. He is
      now waiting for surgical correction of a secundum atrial septal defect.

PMID- 16786799
TI  - [The bilateral breast cancer in patient treated for Ewing sarcoma in childhood-
      the case report].
AB  - This paper presents a patient with bilateral breast cancer who was treated for
      Ewing sarcoma in childhood.

PMID- 16786800
TI  - [Solid and papillary epithelial neoplasm of the pancreas--a rare malignant tumor
      of pancreas].
AB  - The paper presents two cases of solid and papillary epithelial neoplasm of the
      pancreas (SPENP)--a rare pancreatic neoplasm in a 45-year-old woman admitted to
      the hospital with the diagnosis of pancreatic tail tumor and 22-year-old woman
      with the diagnosis of pancreatic head tumor. First patient was subjected to
      peripheral pancreatic resection; the second patient was subjected to Whipple
      pancreatoduodenectomy. Histopathological examination confirmed SPENP. The authors
      present cases and review of the literature on SPENP.

PMID- 16786801
TI  - [Chronic myelomonocytic leukema with gingival hyperplasia--a case report].
AB  - The article reports the case of a patient with chronic myelomonocitic leukemia
      whose first complaint was gingival hyperplasia.

PMID- 16786802
TI  - [Endocrinology complications of Langerhans cell histiocytosis].
AB  - The aim of presentation is an unusual case report of a 17 year old boy with short
      statured (SD (-)4), absent puberty and thyroid enlargement. Endocrine tests
      demonstrated a growth hormone and gonadotropin deficiency with diabetes
      insipidus. Magnetic resonance imaging showed a small pituitary gland and an
      absence of the posterior bright signal. Fine needle aspiration cytology of the
      focus localized in the left lobe of thyroid gland and nearest enlarged lymph
      nodes revealed diffuse infiltrate by the large histiocytosis confirming
      Langerhans cell histiocytosis like in the skin histological specimen biopsy.
      After chemotherapy we observed a regretion of focal changes in the thyroid.

PMID- 16786803
TI  - [An outline of history of rectal surgery].
AB  - An outline of the history of rectal surgery since the XIX century to the present
      day has been presented. Evolution of the opinions in rectal surgery have been
      recalled. Development of surgical technique has been presented. Technical
      achievements in surgery, which pushed possibilities of surgical treatment in
      rectal cancer patients, has been described.

PMID- 16786804
TI  - [Priest Sebastian Kneipp and his hydrotherapeutic method. Point of view after
      over one hundred years].
AB  - Vincenz Priestnitz (1799-1851) and Wilhelm Winternitz (1835-1905) were creators
      of world hydrotherapy. Sebastian Kneipp (1821-1893), the priest at Worishofen,
      the owner of the hydro-therapeutic infirmary where are found precursors of many
      hydro-therapeutic methods. He was the author of several popular books based on
      his experience. The book "My water treatment" is best known. He was also a
      builder of the curative houses, such as: Sebastianeum, Kneip pianeum, Kinder
      Asyl. About 25 thousand people from far-away lands yearly were Kneipp's patients.
      Pourning, wrapings, compresses, rinsing off, total-baths and partial-baths were
      used often. The aim of this paper is to present Kneipp's silhouette and his
      sometimes uncritical hydro-therapeutic methods.

PMID- 16786805
TI  - [The reception of Sebastian Kneipp's hydrotherapeutic method. Its significance in
      contemporary medicine].
AB  - The reports of Wladyslaw Jasinski (1827-1903), Jozef Surzycki (1855-1937) and
      Jozef P. Drzewiecki (1860-1907), XIX century Polish physicians from the
      hydrotherapeutic infirmary in Worishofen are described with full particulars. The
      Kneipp's hydrotherapeutic methods are presented in more details. The Worishofen's
      physicians at that time are outlined. The critical view of therapeutic methods in
      Worishofen by Polish physicians is depicted. The importance of hydrotherapeutic
      methods for contemporary and present medicine is thoroughly described.

PMID- 16786806
TI  - Finding an effective structure for perioperative clinical leadership.

PMID- 16786807
TI  - How to make a business case for new surgical technology.

PMID- 16786808
TI  - Finding a balance for specialty teams.

PMID- 16786809
TI  - Staff input key to specialty team success.

PMID- 16786810
TI  - AORN updates sterilization guideline.

PMID- 16786812
TI  - Successful managed care contracting.

PMID- 16786811
TI  - Is that patient's postoperative skin injury really a burn?

PMID- 16786813
TI  - Characterization of the facial expression of emotions in schizophrenia patients:
      preliminary findings with a new electromyography method.
AB  - OBJECTIVE: We investigated facial expression of emotions (FEE) in schizophrenia
      patients, using an improved and highly selective facial electromyography (EMG)
      method, and we examined the correlation between FEE and psychopathology. METHOD:
      We compared unmedicated patients with schizophrenia (n = 32) with healthy
      subjects (n = 21) with regard to the activity of 3 joy-relevant facial muscles
      (the M.zygomaticus, the M. orbicularis oculi, and the M.levator labii). Emotions
      were induced by pictures from the International Affective Picture System. We
      measured previsible muscle activity with a new, highly selective facial EMG. We
      used the Positive and Negative Syndrome Scale to evaluate psychopathology.
      RESULTS: Patients with schizophrenia showed fewer joy or smile reactions than did
      control subjects and displayed decreased activity of the M.orbicularis oculi and
      M.zygomaticus under presentation of positive pictures. Reduced activity of these
      muscles can be caused by depression. Increased activity of the M. levator labii
      correlates with positive symptoms. CONCLUSIONS: Our findings indicate that
      psychopathological syndromes correlate with schizophrenic mimic disturbances.
      These results can be used to compare various antipsychotics with regard to their
      influence on mimic disturbances.

PMID- 16786814
TI  - Genetic associations between delusional disorder and paranoid schizophrenia: A
      novel etiologic approach.
AB  - OBJECTIVES: Genetic associations between delusional disorder and paranoid
      schizophrenia are not well understood, although involvement of biological factors
      has been suspected. We investigated the incidence of human leukocyte antigen
      (HLA) class I alleles in patients with delusional disorder and paranoid
      schizophrenia, first, to explore a possible immunogenetic etiology of these
      paranoid disorders and, second, to determine whether they share similar etiologic
      mechanisms. METHOD: We employed a nested case-control study design. Psychiatric
      reference data were available for 38,500 patients attending a hospital-based
      psychiatric outpatient department between 1998 and 2005. We enrolled 100 patients
      with delusional disorder and 50 patients with paranoid schizophrenia as the
      subject cases, using DSM-IV criteria. We considered equivalent numbers of healthy
      volunteers matched for age and ethnic background as control subjects. All
      subjects came from an India-born Bengali population. We applied the polymerase
      chain reaction-based molecular typing method to all patients and healthy
      subjects. RESULTS: The HLA-A*03 gene is significantly associated with delusional
      disorder as well as with paranoid schizophrenia. This HLA gene alone or in
      linkage disequilibrium with other HLA genes or other closely linked non-HLA genes
      may influence susceptibility to delusional disorder and paranoid schizophrenia.
      CONCLUSIONS: The study reveals important associations between HLA genes and
      paranoid disorders. Delusional disorder and paranoid schizophrenia may share
      similar etiologic mechanisms. This preliminary observation may help our
      understanding of the genetic basis of these paranoid disorders.

PMID- 16786815
TI  - An epidemiologic study of posttraumatic stress disorder in flood victims in Hunan
      China.
AB  - OBJECTIVE: To estimate the occurrence and to assess the determinants of
      posttraumatic stress disorder (PTSD) in flood victims. METHOD: We carried out a
      retrospective study to examine the occurrence and the determinants of PTSD in
      victims of flood in 1998 and 1999 in Hunan, China. We used multistage sampling to
      select the subjects from the flood areas, and we ascertained PTSD according to
      DSM-IV criteria. Data were collected in face-to-face interviews carried out by
      experienced research assistants using a preconstructed questionnaire. We used a
      multiple logistic regression model to analyze the data. RESULTS: A total of 33
      340 subjects (86.0% of the selected subjects, aged 7 years or over) in the study
      villages were interviewed. Among them, 2875 (8.6%) had symptoms that met the
      diagnostic criteria for PTSD. Significant risk factors for PTSD included female
      sex (odds ratio [OR] 1.12; 95% confidence interval [CI], 1.04 to 1.21), older age
      (age 18 to 59 years OR 2.28; 95%CI, 2.02 to 2.57, and age > or = 60 years OR
      2.42; 95%CI, 2.05 to 2.85), flood type (collapsed embankment OR 1.84; 95%CI, 1.64
      to 2.05, and flash flood OR 3.12; 95%CI, 2.76 to 3.52), and flood severity
      (intermediate OR 4.05; 95%CI, 3.55 to 4.62, and severe OR 2.98; 95%CI, 2.60 to
      3.41). CONCLUSIONS: PTSD is a common mental disorder in flood victims, which
      implies the need for improved health services, especially mental health services,
      for this population.

PMID- 16786816
TI  - Influence of family therapy on bullying behaviour, cortisol secretion, anger, and
      quality of life in bullying male adolescents: A randomized, prospective,
      controlled study.
AB  - OBJECTIVE: To determine the influence of brief strategic family therapy (BSFT) on
      salivary cortisol, anger, and health-related quality of life (QoL) in adolescent
      boys with bullying behaviour. METHOD: We selected a sample of 72 boys
      demonstrating bullying behaviour from the general population and treated 36 with
      BSFT for 12 weeks. The other 36 boys formed the control group. Primary outcome
      measures were salivary cortisol concentration 15 to 30 minutes after awakening
      and changes on the subscales of the State-Trait Anger Expression Inventory
      (STAXI) and the Health Survey (SF-36). RESULTS: After 12 weeks' treatment, we
      observed a significant reduction in bullying behaviour in the BSFT group (P =
      0.017) and in the mean values (according to the intent-to-treat principle) for
      salivary cortisol concentration (P < 0.001). The BSFT group also showed
      significantly greater change on the STAXI subscales State-Anger (P < 0.001),
      Trait-Anger (P < 0.001), Anger-Out (P < 0.001), and Anger-Control (P < 0.001).
      Treatment with BSFT also resulted in significant improvement on the SF-36
      subscales for Vitality (P < 0.001), Social Functioning (P < 0.001), Role
      Emotional (P < 0.001), and Mental Health (P < 0.001). CONCLUSIONS: BSFT
      effectively influenced bullying behaviour, salivary cortisol concentration,
      anger, and health-related QoL in adolescent bullying boys.

PMID- 16786817
TI  - Pharmacologic response to a diagnosis of late-life depression: A population study
      in Quebec.
AB  - OBJECTIVE: To identify predictors of receiving psychoactive medication and
      receiving recommended first-line pharmacotherapy in individuals with newly
      diagnosed late-life depression. METHODS: We undertook a retrospective database
      cohort study of 5258 beneficiaries of the Quebec provincial health insurance plan
      between 1999 and 2002. Subjects were aged 65 to 84 years and diagnosed with
      depression by primary care physicians or psychiatrists between October 2000 and
      March 2001; they had no depression diagnosis in the previous year. We defined
      receipt of psychoactive medication as having a pharmacy claim in the year
      following the depression diagnosis. We determined receipt of recommended first
      line pharmacotherapy from the first psychoactive medication dispensed following
      diagnosis and defined it accordingly; we defined first-line pharmacotherapy
      according to the 2001 Canadian Psychiatric Association guidelines. We used
      multivariate generalized estimating equations models to identify the determinants
      of the 2 outcomes. RESULTS: A total of 4421 (84.1%) patients received
      psychoactive medication following diagnosis; 2623 (59.3%) patients had not
      received antidepressants in the previous year. Of these, 1310 (49.9%) received
      recommended first-line pharmacotherapy. Independent predictors of receiving
      psychoactive medication were female sex, depression not otherwise specified
      (NOS), increasing comorbidity, and living in rural areas. Independent predictors
      of receiving recommended first-line pharmacotherapy were male sex, depression
      NOS, receiving medication in the month following diagnosis, and having the same
      physician diagnosing and treating the patient. CONCLUSION: Male sex and
      continuity of care predicted that patients had the recommended medication
      dispensed.

PMID- 16786818
TI  - Corrected QT intervals in newly admitted geriatric psychiatric patients: an
      examination of risk factors.
AB  - OBJECTIVES: The primary objective of this study was to determine the incidence of
      prolonged corrected QT (QTc) intervals in a population of geriatric psychiatry
      inpatients. Our secondary objective was to examine the associations between
      prolonged QTc intervals and risk factors identified as determinants in prolonging
      the QTc interval. METHODS: We identified all geriatric patients (aged 60 years
      and older) who were admitted to the geriatric program of our facility between May
      1, 2003, and December 31, 2003. Those patients with a heart rate QTc interval
      calculated on the electrocardiogram (ECG) were eligible for the study. We used
      Bazett's formula to calculate the QTc interval. We defined a priori that a
      prolonged QTc interval would be 450 ms and 460 ms for men and women,
      respectively. We collected data on demographic variables such as weight, sex,
      age, and Axis I and III diagnoses, as well as on recognized risk factors for
      prolonged QTc interval. We used Student's t tests to conduct parametric analysis
      on continuous variables, and chi-square to test categorical variables for
      independence. RESULTS: During the study period, 88 patients were admitted to the
      geriatric division of Riverview Hospital. Of these patients, 34 men and 42 women
      had calculated QTc intervals on their ECG and therefore made up the study
      population. Our data show that 29.4% of men and 21.4% of women had prolonged QTc
      intervals. However, neither diagnostic nor medicinal risk factors were found to
      be associated with an increased incidence of prolonged QTc interval in this
      patient population. CONCLUSION: The preliminary findings of this study suggest
      that in this patient population the QTc interval may not be influenced by
      recognized risk factors to the same extent as observed in the adult population.
      These results warrant confirmation by a larger, prospectively designed study.

PMID- 16786819
TI  - Canadian psychiatry residency training programs: A glance at the management
      structure.
AB  - OBJECTIVES: To describe the administrative functioning of all current Canadian
      psychiatry residency training programs (RTPs) and to suggest available
      improvements to existing systems. METHOD: We obtained data about the 2004 RTPs by
      distributing 2 questionnaires to all Canadian psychiatry RTPs. RESULTS: Residency
      program committees (RPCs) are mainly consultative and carry only a small amount
      of the workload of managing a residency program. Program directors (PDs) manage
      more than 80% of the work and report that the time allowance to perform their
      duties is suboptimal. PDs remain in office for about 5 years, departing during or
      at the end of a predetermined second term. CONCLUSION: RPCs bear only a small
      amount of the workload generated by the RTP. We piloted administrative changes
      that led to more equitable work distribution.

PMID- 16786820
TI  - Insulin resistance and adiponectin levels in drug-free patients with
      schizophrenia: A preliminary report.
AB  - OBJECTIVE: To compare the insulin sensitivity and adiponectin levels of
      medication-free patients suffering from schizophrenia or schizoaffective disorder
      with that of matched healthy volunteers. METHOD: We evaluated 9 nondiabetic
      patients aged 26.6 years (median 26 years, range 17 to 41 years) and matched
      volunteers, using the frequently sampled intravenous glucose tolerance test,
      minimal model analysis, and fasting adiponectin levels. RESULTS: The mean insulin
      sensitivity index of the patients was 42% lower than that of the healthy
      volunteers (P = 0.026), with inadequate compensation in insulin secretion.
      Patients with schizophrenia tended to have reduced adiponectin levels (P =
      0.055). CONCLUSIONS: By direct measurement, this study provides evidence of
      insulin resistance and susceptibility to type 2 diabetes in patients with
      schizophrenia who are free of antipsychotic drugs.

PMID- 16786821
TI  - Detection of depression in acute schizophrenia: sensitivity and specificity of 2
      standard observer rating scales.
AB  - OBJECTIVE: To compare the psychometric properties of the Calgary Depression
      Rating Scale (CDRS) and the Hamilton Depression Rating Scale (HDRS) for severity
      assessment of depression in acute schizophrenia. METHOD: During clinical routine
      treatment, we investigated 119 inpatients with acute schizophrenia, using the
      CDRS, the HDRS, and a global 4-point Depression Severity Scale (DEP-SEV). We
      compared CDRS and HDRS sum scores regarding their diagnostic accuracy, with
      global severity of depression as the criterion. We estimated sensitivity and
      specificity on the basis of receiver operating characteristic curves. RESULTS:
      According to global clinical ratings (DEP-SEV), 31% of patients had no
      depression, 19% had mild, 31% had moderate, and 19% had severe depression.
      Sensitivity was significantly higher (P < 0.05) for the CDRS than for the HDRS to
      assess mild (0.94 vs 0.76, cut-off 3 vs 10 points) or severe depression (1.00 vs
      0.78, cut-off 11 vs 22 points); specificity was comparably high (> or = 0.88) for
      both scales. CONCLUSION: Despite the fact that both scales were effective in
      separating mild, moderate, and severe depression, significant advantages emerged
      for the CDRS to detect mild or severe depression in schizophrenia.

PMID- 16786822
TI  - Characterization and treatment response of anxious children with asthma.
AB  - OBJECTIVES: To compare children with Axis I anxiety disorders and asthma with a
      matched group of anxious children without asthma on questionnaire measures and
      response to cognitive-behavioural treatment (CBT) for anxiety. METHOD: A sample
      of 36 children with comorbid anxiety and asthma, aged 8 to 12 years, were matched
      for age, sex, and specific anxiety disorder with 36 children with an Axis I
      anxiety disorder but no asthma. Parents and children completed standardized
      questionnaires. RESULTS: Children with comorbid anxiety and asthma had
      significantly more perinatal complications (P = 0.001), and higher total (P =
      0.000) and psychological stressors (P = 0.02), especially parent-child problems
      (P = 0.01), but lower levels of depression (P = 0.03) and anxiety (P = 0.05),
      compared with anxious, nonasthmatic children. All children reported decreased
      anxiety (P = 0.001) and depression (P = 0.000) posttreatment, with a trend toward
      less improvement in anxiety in anxious children with asthma. CONCLUSIONS:
      Although replication is needed, addressing psychosocial stress and parent-child
      problems may increase CBT efficacy in children with comorbid anxiety and asthma.

PMID- 16786823
TI  - Re: troubles in traumatology, and debunking myths about trauma and memory.

PMID- 16786824
TI  - Better practices in collaborative mental health care: an analysis of the evidence
      base.
AB  - OBJECTIVES: To conduct a systematic review of the experimental literature in
      order to identify better practices in collaborative mental health care in the
      primary care setting. METHODS: A review of Canadian and international literature
      using Medline, PsycInfo, Embase, the Cochrane Library, and other databases
      yielded over 900 related reports, of which, 38 studies met the inclusion
      criteria. A systematic review and descriptive analysis is presented, with key
      conclusions and best practices. RESULTS: Successful collaboration requires
      preparation, time, and supportive structures, building on preexisting clinical
      relationships. Collaborative practice is likely to be most developed when
      clinicians are colocated and most effective when the location is familiar and
      nonstigmatizing for patients. Degree of collaboration does not appear to predict
      clinical outcome. Enhanced collaboration paired with treatment guidelines or
      protocols offers important benefits over either intervention alone in major
      depression. Systematic follow-up was a powerful predictor of positive outcome in
      collaborative care for depression. A clear relation between collaborative efforts
      to increase medication adherence and clinical outcomes was not evident.
      Collaboration alone has not been shown to produce skill transfer in PCP knowledge
      or behaviours in the treatment of depression. Service restructuring designed to
      support changes in practice patterns of primary health care providers is also
      required. Enhanced patient education was part of many studies with good outcomes.
      Education was generally provided by someone other than the PCP. Collaborative
      interventions that are part of a research protocol may be difficult to sustain
      long-term without ongoing funding. Consumer choice about treatment modality may
      be important in treatment engagement in collaborative care (for example, having
      the option to choose psychotherapy vs medication). CONCLUSIONS: A body of
      experimental literature evaluating the impact of enhanced collaboration on
      patient outcomes-primarily in depressive disorders-now exists. Better practices
      in collaborative mental health care are beginning to emerge.

PMID- 16786825
TI  - Where oh where...?

PMID- 16786826
TI  - Why a well-paid nurse is a better nurse.
AB  - In an article subtitled "Why is a Badly Paid Nurse a Good Nurse?" economist
      Anthony Heyes argues that nursing wages should be kept low. Counter arguments are
      provided based on what the authors consider more adequate economic analysis.

PMID- 16786827
TI  - Which pasture is really greener? A research note on salary studies.
AB  - National and regional studies of nurse salaries often draw conclusions based
      solely on the dollar values reported. This brief research note shows the
      importance of including information about the cost of living into any comparative
      analysis of geographic differences in salaries.

PMID- 16786828
TI  - ADN to BSN: lessons from human capital theory.
AB  - Currently, approximately 16% of associate degree nursing (ADN) graduates acquire
      baccalaureate or higher degrees. Human capital analysis demonstrated negative to
      minimal average returns on investment (ROI) in BSN education. Increasing the ROI
      may influence ADNs to pursue baccalaureate education and can be an effective
      strategy for meeting the projected need for BSN-prepared nurses.

PMID- 16786829
TI  - Overcoming barriers to patient safety.
AB  - Creating a culture of patient safety is a critical goal of all patient care unit
      staff. An analysis of the key barriers to patient safety on a typical inpatient
      unit in an acute care hospital (unclear unit values), the fear of punishment for
      errors, the lack of systematic analysis of mistakes, the complexity of the
      nurses' work, and inadequate teamwork are presented. Nine practices to overcome
      these barriers and achieve patient safety are discussed.

PMID- 16786831
TI  - Paving and resurfacing the road to Magnet: part II.

PMID- 16786832
TI  - Securing successful funding for nursing research through the Agency for
      Healthcare Research and Quality.

PMID- 16786830
TI  - Graduate nurse perceptions of the work experience.
AB  - Findings from a longitudinal study on the perceptions of the work environment and
      job satisfaction for new graduate nurses in the first 18 months of employment at
      a Magnet Midwestern urban academic pediatric medical center are described. The
      findings indicated that orientation assisted the new graduate to become confident
      in his/her clinical competence and work management. By 18 months, the new
      graduate felt satisfied with access to resources and the ability to participate
      in professional development opportunities. The results suggest that the new
      graduate nurse's career adjustment extends beyond mastering clinical skills and
      includes a lifestyle adjustment to a profession that requires service 24 hours a
      day, 7 days a week.

PMID- 16786833
TI  - Creating partnerships through Patient Safety Awareness Week.

PMID- 16786834
TI  - Stories as motivators.

PMID- 16786835
TI  - Beyond busyness: creating slack in the organization.
AB  - Human beings are not machines. The patient safety literature documents the price
      we pay for excessive overtime, long hours, and no breaks. Disengaged staff, high
      vacancy rates, and turnover are the products of cultures that do not support a
      professional environment where nurses are seen as knowledge workers. At his
      retirement dinner, a factory worker accepted accolades for his years of dedicated
      service. In his farewell speech, he noted that for 40 years the factory used his
      hands but never his brains. His expertise and knowledge were never acknowledged
      or solicited. Consequently he watched in silence for years as directives came
      down from managers and leaders that were totally unrealistic and bore no
      relevance to the reality in which he worked. And he watched the initiatives fail.
      Unfortunately we in health care can create that exact situation if we do not
      incorporate time (slack) into the schedules of our knowledge workers so they can
      unleash their genius, reinvent health care, and fix health care from the inside
      out. Nurse leaders must be the architects of participation and allow this to
      happen.

PMID- 16786836
TI  - Photoirradiation of representative polycyclic aromatic hydrocarbons and twelve
      isomeric methylbenz[a]anthracene with UVA light: formation of lipid peroxidation.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widespread genotoxic environmental
      pollutants, which require metabolic activation in order to exert biological
      activities, including mutagenicity and carcinogenicity. Photoactivation is
      another activation pathway that can lead to PAH genotoxicity. In this paper, we
      demonstrate that photoirradiation of a series of representative PAHs, with and
      without bearing a methyl substituent, with UVA light in the presence of methyl
      linoleate resulted in the formation of methyl linoleate hydroperoxides (a lipid
      peroxide). The lipid peroxide formation was inhibited by dithiothreitol (DTT)
      (free radical scavenger), NaN3 (singlet oxygen and free radical scavenger), and
      superoxide dismutase (SOD) (superoxide scavenger), but was enhanced by the
      presence of deuterium oxide (D2O) (extends singlet oxygen lifetime). These
      results suggest that photoirradiation of PAHs by UVA light generates reactive
      oxygen species (ROS), which induce lipid peroxidation.

PMID- 16786837
TI  - Prominent free radicals scavenging activity of tannic acid in lead-induced
      oxidative stress in experimental mice.
AB  - Lead (Pb) is known to disrupt the pro-oxidant/antioxidant balance of tissues
      leading to biochemical and physiological dysfunction. The present study was
      designed to investigate the effect of tannic acid on some biochemical parameters
      in Swiss albino mice exposed to lead acetate. The levels of thiobarbaturic acid
      reactive substances (TBARS) as an index of lipid peroxidation, nitric oxide (NO),
      and serum lead (Pb) were significantly increased following intragastric
      administration of 50 micromole lead acetate/kg body weight three times a week,
      every other day for three weeks, compared to the corresponding control values. On
      the other hand, the activities of superoxide dismutase (SOD), catalase (CAT),
      glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione
      content (GSH) and serum copper (Cu) and zinc (Zn) were significantly diminished
      relative to the control values. The administration of 20 mg tannic acid/kg body
      weight three times a week every other day for three weeks, enhanced the
      endogenous antioxidant capacity of the cells by increasing the activities of
      antioxidant enzymes (SOD, CAT, GSH-R, GST), GSH content and serum Cu and Zn
      levels. Compared to the lead acetate-exposed group, the levels of TBARS, NO and
      Pb were decreased in the lead acetate exposed group treated with tannic acid.
      These results afford evidence supporting the hypothesis that lead induces
      oxidative stress in hepatic cells. Moreover, tannic acid has a potential in
      sustaining global antioxidant effect in hepatic cells leading to decreased
      oxidative stress and cellular damage initiated through free radical production by
      lead acetate.

PMID- 16786838
TI  - The rate-limiting step in anaerobic digestion in the presence of phosphine.
AB  - Methanogenesis is the most important anaerobic biodegradation process in nature,
      which is accomplished by three different kinds of bacteria - hydrolytic,
      acetogenic and methanogenic bacteria (MB). An experiment was performed to
      determine the rate-limiting step of methanogenesis under the influence of various
      phosphine concentrations (100, 300, 500, 700 and 1000 ppm). It was found that the
      growth of fermentative bacteria (FB) was severely affected by higher
      concentrations of phosphine (700 and 971 ppm), while the growth of hydrogen
      producing acetogenic bacteria (HPAB) and MB was not affected severely at higher
      phosphine concentrations. Thus, HPAB and MB are less sensitive to phosphine
      compared with FB, which means that hydrolysis, and fermentation step is the rate
      limiting step during methanogenesis under the influence of phosphine. It is
      recommended that special attention be paid to the first stage of methanogenesis
      under high concentrations of phosphine during anaerobic wastewater treatment.

PMID- 16786839
TI  - The protective effect of hydrated sodium calcium aluminosilicate against the
      adverse effects of aflatoxin B1 on D. melanogaster.
AB  - The main aim of this study was to investigate the effects of Aflatoxin B1 (AFB1)
      and Aflatoxin B1 + hydrated sodium calcium aluminosilicate (HSCAS) on various
      developmental stages of Drosophila melanogaster. Different concentrations of AFB1
      and HSCAS + AFB1 were administered during the developmental periods of the fly
      (egg, larvae and pupae). When the F1 progeny of control and application groups
      were compared, AFB1 was found to extend the process of metamorphosis and decrease
      the total number of offspring. However, these negative effects were inhibited
      with HSCAS treatment at different concentrations (5.0 and 10.0 ppm). These
      results suggest that HSCAS could effectively inhibit AFB1-induced abnormalities
      in the developmental stages of D. melanogaster.

PMID- 16786840
TI  - Levels of retinyl palmitate and retinol in the stratum corneum, epidermis, and
      dermis of female SKH-1 mice topically treated with retinyl palmitate.
AB  - Retinyl esters are the storage form of vitamin A in skin, and retinyl palmitate
      (RP) accounts for the majority of the retinyl esters endogenously formed in skin.
      RP is also obtained exogenously through the topical application of cosmetic and
      skin care products that contain RP. There is limited information on the
      penetration and distribution of RP and vitamin A within the stratified layers of
      the skin. The purpose of these studies was to determine the time course for
      accumulation and disappearance of RP and retinol in the stratified layers of skin
      from female SKH-1 mice that received single or repeated topical applications of
      creams containing 0.5 or 2% of RP. We developed an HPLC method with detection
      limits of 5.94 and 1.62 ng, to simultaneously quantify the amount of RP and
      retinol, respectively, in skin samples. Our results showed that RP rapidly
      diffuses into the stratum corneum and epidermal skin layers within 24 h following
      the application of RP-containing creams. Of the three skin layers, the highest
      level of RP and retinol per weight unit (ng/mg) at all time points was found in
      the epidermis. Levels of RP and retinol were lowest in the dermal layer and
      intermediate in the stratum corneum. The levels of RP and retinol in the
      separated skin layers and in the intact skin decreased with time, but levels of
      RP remained higher than control values for a period of up to 18 days. Our results
      indicate that the application of RP to mouse skin alters the normal physiological
      levels of RP and retinol in the skin.

PMID- 16786841
TI  - Molecular characterization of Escherichia coli O157:H7 hide contamination routes:
      feedlot to harvest.
AB  - This study was conducted to identify the origin of Escherichia coli O157:H7
      contamination on steer hides at the time of harvest. Samples were collected from
      the feedlot, transport trailers, and packing plant holding pens and from the
      colons and hides of feedlot steers. A total of 50 hide samples were positive for
      E. coli O157:H7 in two geographical locations: the Midwest (25 positive hides)
      and Southwest (25 positive hides). Hide samples were screened, and the presence
      of E. coli O157: H7 was confirmed. E. coli O157:H7 isolates were fingerprinted by
      pulsed-field gel electrophoresis and subjected to multiplex PCR procedures for
      amplification of E. coli O157:H7 genes stx1, stx2, eaeA, fliC, rfbEO157, and
      hlyA. Feedlot water trough, pen floor, feed bunk, loading chute, truck trailer
      side wall and floor, packing plant holding pen floor and side rail, and packing
      plant cattle drinking water samples were positive for E. coli O157:H7. Pulsed
      field gel electrophoresis banding patterns were analyzed after classifying
      isolates according to the marker genes present and according to packing plant. In
      this study, hide samples positive for E. coli O157:H7 were traced to other E.
      coli O157:H7-positive hide, colon, feedlot pen floor fecal, packing plant holding
      pen drinking water, and transport trailer side wall samples. Links were found
      between packing plant side rails, feedlot loading chutes, and feedlot pens and
      between truck trailer, different feedlots, and colons of multiple cattle. This
      study is the first in which genotypic matches have been made between E. coli
      O157:H7 isolates obtained from transport trailer side walls and those from cattle
      hide samples within the packing plant.

PMID- 16786842
TI  - Transfer coefficient models for escherichia coli O157:H7 on contacts between beef
      tissue and high-density polyethylene surfaces.
AB  - Risk studies have identified cross-contamination during beef fabrication as a
      knowledge gap, particularly as to how and at what levels Escherichia coli O157:H7
      transfers among meat and cutting board (or equipment) surfaces. The objectives of
      this study were to determine and model transfer coefficients (TCs) between E.
      coli O157:H7 on beef tissue and high-density polyethylene (HDPE) cutting board
      surfaces. Four different transfer scenarios were evaluated: (i) HDPE board to
      agar, (ii) beef tissue to agar, (iii) HDPE board to beef tissue to agar, and (iv)
      beef tissue to HDPE board to agar. Also, the following factors were studied for
      each transfer scenario: two HDPE surface roughness levels (rough and smooth), two
      beef tissues (fat and fascia), and two conditions of the initial beef tissue
      inoculation with E. coli O157:H7 (wet and dry surfaces), for a total of 24
      treatments. The TCs were calculated as a function of the plated inoculum and of
      the cells recovered from the first contact. When the treatments were compared,
      all of the variables evaluated interacted significantly in determining the TC. An
      overall TC-per-treatment model did not adequately represent the reduction of the
      cells on the original surface after each contact and the interaction of the
      factors studied. However, an exponential model was developed that explained the
      experimental data for all treatments and represented the recontamination of the
      surfaces with E. coli O157:H7. The parameters for the exponential model for cross
      contamination with E. coli O157:H7 between beef tissue and HDPE surfaces were
      determined, allowing for the use of the resulting model in quantitative microbial
      risk assessment.

PMID- 16786843
TI  - Growth performance and shedding of some pathogenic bacteria in feedlot cattle
      treated with different growth-promoting agents.
AB  - Eighty steers with a mean body weight of 319 kg were used in a study to evaluate
      the effect of a growth-promoting implant (trenbolone acetate plus estradiol
      benzoate), monensin, and oxytetracycline on the steer performance and shedding of
      some foodborne pathogens. The steers were allotted to one of eight treatment
      combinations according to a randomized complete block design with 16 pens of five
      animals. Rectal fecal samples were collected before treatment commenced and over
      a period of more than 24 weeks to study the influence of treatments on the
      intestinal microbiology of the animals. Results supported the beneficial effect
      of the hormonal implant on the performance of feedlot steers (average daily gain,
      feed efficiency, and fat thickness), on carcass characteristics (hot carcass
      weight, lean yield), and economic value of the carcasses (P < 0.01). The levels
      of Escherichia coli in feces were not affected by treatments but remained high
      throughout the study period. Antibiotic-resistant isolates of E. coli were more
      frequently found as the study progressed but were not associated with any
      specific treatment. Also independently of treatment, we observed a reduction over
      time in the shedding of Campylobacter and Yersinia during the feeding period,
      whereas the shedding of Enterococcus was increased. The results of this study
      confirmed the beneficial economic effect of growth-promoting agents in beef
      production and showed that the agents tested did not specifically affect the
      overall microbial evolution of the animal gut. However, the study also showed,
      independently of the growth promoter used, the shedding of Campylobacter,
      Yersinia, and antibiotic-resistant E. coli in the feedlot environment. These
      bacteria also may be found in the colonic tissue of steers at slaughter and might
      be a source of carcasses contamination.

PMID- 16786844
TI  - A rapid molecular-based assay for direct quantification of viable bacteria in
      slaughterhouses.
AB  - A rapid test for microbial quantification in carcass and environmental swabs that
      does not require enrichment and provides results in less than 4 h is described
      here. Steps in the assay include the rapid concentration of bacteria on sponge
      swabs by vacuum filtration followed by real-time PCR detection. The assay has
      been applied for the detection of coliforms, Escherichia coli O157:H7, Salmonella
      spp., and Listeria monocytogenes on carcass swabs and environmental samples in a
      slaughterhouse-processing line. Comparison of this rapid method with standard
      culture techniques for coliform counts on beef and pork carcass swabs revealed
      higher numbers of bacteria (2- to 50-fold) by the rapid test compared with the
      plate counts. This was due to the detection of all bacteria (live, dead, and non
      culturable forms) in the rapid assay. To allow detection of only viable bacteria,
      concentrated samples were treated with ethidium monoazide (EMA) prior to DNA
      extraction and real-time PCR detection, thereby preventing the amplification of
      DNA from bacteria with damaged cell walls and allowing only the DNA from bacteria
      with intact membranes to be detected. EMA treatment resulted in a significant
      reduction (P < 0.001) in the number of coliforms detected compared to real-time
      PCR without EMA treatment. In beef swabs, the counts obtained in EMA real-time
      PCR were not significantly different (P < 0.08) from the culture counts and the
      correlation coefficient between the two assays was 0.7385. A lower correlation
      coefficient (0.402) was obtained with pork swabs. The assay described herein has
      the potential to be applied on a routine basis to slaughterhouse lines for the
      detection of indicator organisms or specific pathogens.

PMID- 16786845
TI  - Fate of inoculated Escherichia coli O157:H7, cultured under different conditions,
      on fresh and decontaminated beef transitioned from vacuum to aerobic packaging.
AB  - This study evaluated the behavior of Escherichia coli O157:H7 during aerobic
      storage, after storage in vacuum packages, on beef inoculated with cultures
      prepared (35 degrees C, 24 h) in tryptic soy broth without dextrose (TSB),
      nonacid hot water carcass decontamination runoff fluids (washings; pH 6.0; WASH),
      cells from biofilms formed on stainless steel coupons in WASH (WETB), or WETB
      dried (25 degrees C, 12 h) before harvesting of cells (DRYB). These inocula were
      applied to fresh beef pieces (40 cm2), which were then left untreated or treated
      by immersion in hot water (75 degrees C) followed by 2% lactic acid (55 degrees
      C; hot water/lactic acid [HW/LA]), for 30 s each. Inoculated samples were vacuum
      packaged and stored at 0 (30, 60, or 90 days), 4 (7 or 14 days), or 12 degrees C
      (4 or 8 days) and subsequently transferred to retail packages for aerobic storage
      at 7 degrees C for 5 days. Populations of E. coli O157:H117, regardless of
      inoculum type, remained generally unchanged (P > 0.05) after aerobic storage (7
      degrees C, 5 days) of untreated or HW/LA-treated beef samples previously stored
      in vacuum packages at 0 or 4 degrees C. However, reductions in E. coli O157:H7
      levels were generally obtained when vacuum packaged, untreated beef samples
      previously stored at 12 degrees C were transitioned to aerobic conditions.
      Additionally, despite similar (P > 0.05) levels of E. coli O157:H7 cells of TSB,
      WASH, WETB, and DRYB origin on vacuum-packaged, untreated samples after 8 days of
      storage at 12 degrees C, subsequent aerobic storage resulted in larger (P < 0.05)
      reductions of cells of WETB and DRYB origin than for cells of TSB and WASH
      origin. For HW/LA-treated beef previously stored at 12 degrees C in vacuum
      packages, populations of E. coli O157:H7 remained largely unchanged after aerobic
      storage in retail packages. Results thus indicated that aerobic storage of beef
      (7 degees C, 5 days) previously stored in vacuum packages at 0 or 4 degrees C did
      not lead to E. coli O157:H7 population changes, whereas transition from vacuum
      packages stored under mildly abusive temperature (12 degrees C) to aerobic
      storage may have caused injury and death to the pathogen.

PMID- 16786847
TI  - Differential killing activity of cetylpyridinium chloride with or without bacto
      neutralizing buffer quench against firmly adhered Salmonella gaminara and
      Shigella sonnei on cut lettuce stored at 4 degrees C.
AB  - Cetylpyridinium chloride (CPC) activity was quenched with Bacto neutralizing
      buffer on inoculated cut iceberg lettuce. This protocol permitted comparison of
      the numbers of Salmonella Gaminara- or Shigella sonnei-inoculated cells on
      lettuce that survived 1 min of CPC treatment. Cut lettuce was inoculated with
      about 6 log of Salmonella or 9 log of Shigella and stored in Whirl-Pak bags at 4
      degrees C for up to 4 days. Loosely adhered pathogen cells were washed off before
      CPC treatment. Firmly adhered cells of Salmonella Gaminara or S. sonnei on cut
      iceberg lettuce survived treatment with CPC even at the 0.4% CPC level if the CPC
      activity was quenched after 1 min by adding Bacto neutralizing buffer. The
      results confirm that there is extended killing activity of residual CPC against
      Salmonella Gaminara or S. sonnei if the residual CPC remaining in contact with
      the lettuce after the initial 1-min wash is not quenched. The CPC treatment was
      useful in reducing the numbers of these target pathogens on lettuce.

PMID- 16786846
TI  - Phenotypic and genotypic characterization of Salmonella enterica serotype
      paratyphi B isolates from environmental and human sources in Galicia, Spain.
AB  - Salmonella serotype Paratyphi B isolates obtained from shellfish and human
      infections in Galicia (northwest Spain) from 1998 were investigated by different
      phenotypic and genetic methods to evaluate their systemic or enteric nature.
      Isolates were investigated for D-tartrate fermentation, presence of genes
      encoding the effector proteins sopE1 and avrA, pulsed-field gel electrophoresis
      profile, and antimicrobial susceptibility. Systemic variant strains (dT-) were
      the dominant among the marine environment isolates. All dT- isolates were sopE1
      positive and avrA negative, presented an indistinguishable electrophoresis
      profile, and were grouped in a single cluster. More electrophoresis heterogeneity
      was observed among dT+ isolates. Only two isolates showed resistance to any of
      the 16 antibiotics included in our panel. The present study identified the marine
      environment as a potential natural source of systemic variant isolates of
      Salmonella Paratyphi B. The presence of systemic variant isolates of Salmonella
      Paratyphi B in the marine environment is of notable public health significance as
      a result of the potential risk of acquiring enteric fever linked to the
      consumption of raw shellfish.

PMID- 16786848
TI  - Chlorine resistance of Listeria monocytogenes biofilms and relationship to
      subtype, cell density, and planktonic cell chlorine resistance.
AB  - Strains of Listeria monocytogenes vary in their ability to produce biofilms. This
      research determined if cell density, planktonic chlorine resistance, or subtype
      are associated with the resistance of L. monocytogenes biofilms to chlorine.
      Thirteen strains of L. monocytogenes were selected for this research based on
      biofilm accumulation on stainless steel and rep-PCR subtyping. These strains were
      challenged with chlorine to determine the resistance of individual strains of L.
      monocytogenes. Planktonic cells were exposed to 20 to 80 ppm sodium hypochlorite
      in 20 ppm increments for 5 min in triplicate per replication, and the experiment
      was replicated three times. The number of tubes with surviving L. monocytogenes
      was recorded for each isolate at each level of chlorine. Biofilms of each strain
      were grown on stainless steel coupons. The biofilms were exposed 60 ppm of sodium
      hypochlorite. When in planktonic culture, four strains were able to survive
      exposure to 40 ppm of chlorine, whereas four strains were able to survive 80 ppm
      of chlorine in at least one of three tubes. The remaining five strains survived
      exposure to 60 ppm of chlorine. Biofilms of 11 strains survived exposure to 60
      ppm of chlorine. No association of biofilm chlorine resistance and planktonic
      chlorine resistance was observed; however, biofilm chorine resistance was similar
      for strains of the same subtype. Biofilm cell density was not associated with
      chlorine resistance. In addition, biofilms that survived chlorine treatment
      exhibited different biofilm morphologies. These data suggest that chlorine
      resistance mechanisms of planktonic cells and biofilms differ, with planktonic
      chlorine resistance being more affected by inducible traits, and biofilm chlorine
      resistance being more affected by traits not determined in this study.

PMID- 16786849
TI  - Characterization of Listeria monocytogenes isolates from 50 small-scale Austrian
      cheese factories.
AB  - One hundred eighty-one small-scale cheese factories (annual production < 100,000
      kg) were tested for the presence of Listeria monocytogenes in cheese and smear
      samples from 1997 to 2000. In total, 2615 samples were drawn. Fifty (27.6%) of
      181 enterprises yielded L. monocytogenes. From 14 of the cheese-making
      facilities, we obtained more than four L. monocytogenes isolates. A total of 182
      mostly cheese- and smear-borne L. monocytogenes strains were characterized by
      serotyping and pulsed-field gel electrophoresis. In 12 of 14 cheese factories,
      over half of the L. monocytogenes isolates were genetically indistinguishable by
      pulsetype. On average, genetically indistinguishable isolates were recovered for
      11.9 months. Regarding serotypes, 27.3% of the isolates were of serovar 4b.
      Inadequate personal hygiene could explain the high prevalence of serovar 4b
      isolates in small-scale cheesemaking facilities. Forty-two percent of the serovar
      4b isolates recovered from epidemiologically unlinked facilities (in comparison
      to 40 and 29% of the 1/2a and 1/2b isolates, respectively) were genetically
      indistinguishable from at least one other isolate. Indistinguishable serovar 1/2a
      and 1/2b isolates belonged to five and six different pulsetypes, respectively,
      whereas serovar 4b isolates belonged to only two pulsetypes. This finding
      suggested a wide distribution of genetically homologous serovar 4b isolates among
      the facilities tested in our study.

PMID- 16786850
TI  - Contamination of cooked peeled shrimp (Pandalus borealis) by Listeria
      monocytogenes during processing at two processing plants.
AB  - Listeria spp. and Listeria monocytogenes contamination was evaluated in cooked
      peeled shrimp (final or semifinal product, 82 samples) and the shrimp-processing
      environment (two plants, 613 samples) in eight surveys conducted from 1998
      through 2001. Listeria was detected in 12.5% (78) of the 695 samples (11.2% of
      the samples were positive for L. monocytogenes), but none of the samples of final
      product contained Listeria. One hundred seventy-two L. monocytogenes isolates
      were characterized by pulsed-field gel electrophoresis. Cleavage with
      macrorestriction enzymes AscI and ApaI yielded 14 different pulsotypes in the
      plants; two types were dominant, one in each plant. Sixty-three of the 106
      isolates in plant A and 43 of the 66 isolates in plant B were of the dominant
      types. Certain strains, mainly of serotypes 1/2c and 4b and pulsotypes 1A and 2H,
      were persistent for long periods in both plants. Adaptation of good hygienic
      practices in the processing plants, including strict rules concerning traffic of
      staff and equipment, and existing hygienic requirements appeared to be effective
      in preventing contamination between areas within plants and in the final product.
      The persistence of Listeria strains in these two processing plants indicates the
      importance of detecting the places in the processing environment (e.g.,
      transporters, equipment, floors, and drains) where L. monocytogenes can survive
      so that cleaning and disinfection efforts can be directed to such niches.

PMID- 16786851
TI  - Determination of the growth limits and kinetic behavior of Listeria monocytogenes
      in a sliced cooked cured meat product: validation of the predictive growth model
      under constant and dynamic temperature storage conditions.
AB  - To describe the growth limits of Listeria monocytogenes NCTC10527 in a sliced
      vacuum-packaged cooked cured meat product, the binary logistic regression model
      was used to develop an equation to determine the probability of growth or no
      growth of L. monocytogenes as a function of temperature (from 0 to 10 degrees C)
      and water activity (from 0.88 to 0.98). Two inoculum concentrations were used (10
      and 10(4) CFU g(-1)), and the growth limits for the two inocula were different.
      The kinetic behavior of L. monocytogenes as a function of temperature (4, 8, 12,
      and 16 degrees C) on the same meat product at the lower concentration (10 CFU g(
      1)) was also studied. The Baranyi model appeared to fit the overall experimental
      data better than did the modified Gompertz and the modified logistic models.
      Maximum specific growth rate (micromax), lag phase duration (LPD), and maximum
      cell concentration (Nmax) derived from the primary model were modeled using the
      square root function (micromax and LPD) and a second order polynomial (Nmax)
      (secondary models). The selection of the best model (primary or secondary) was
      based on some statistical indices (the root mean square error of residuals of the
      model, the regression coefficient, the F test, the goodness of fit, and the bias
      and accuracy factor). The developed kinetic behavior model was validated under
      constant and dynamic temperature storage conditions. This prediction of L.
      monocytogenes growth provides useful information for improving meat safety and
      can be used for in-depth inspection of quality assurance systems in the meat
      industry.

PMID- 16786852
TI  - Inhibition of Listeria innocua in hummus by a combination of nisin and citric
      acid.
AB  - The effect of nisin or citric acid or combinations of these two inhibitors on the
      inactivation of a cocktail of three Listeria innocua strains was investigated in
      a model brain heart infusion (BHI) broth and hummus (chickpea dip). In BHI broth,
      citric acid had a limited ability to inhibit L. innocua growth. Nisin initially
      reduced L. innocua concentrations by about 3 log cycles; however, L. innocua
      reached concentrations similar to those of the control after 5 days at 22 degrees
      C. In combination, the effects of 500 IU/ml nisin and 0.2% citric acid were
      synergistic and resulted in complete elimination of L. innocua in the BHI broth.
      The inhibition of L. innocua by nisin (500 or 1,000 IU/g), citric acid (0.1, 0.2,
      or 0.3%), or their combinations also was evaluated in hummus. Citric acid alone
      did not affect L. innocua growth or the aerobic bacterial plate count. A
      combination of 1,000 IU/g nisin and 0.3% citric acid was somewhat effective
      (approximately 1.5-log reduction) in controlling the concentration of L. innocua
      and the aerobic plate count for up to 6 days. This combination also may be
      useful, in addition to proper hygienic practices, for minimizing the growth of
      the pathogen Listeria monocytogenes in hummus.

PMID- 16786853
TI  - Effect of cheese water activity and carbohydrate content on the barotolerance of
      Listeria monocytogenes scott A.
AB  - High-pressure processing is an appropriate technique for improving the
      microbiological safety of packaged ready-to-eat foods. The effect of high
      pressure treatment on Listeria monocytogenes Scott A inoculated into fresh
      Hispanico-type cheese and ripe Mahon cheese was investigated. A 3.8-log reduction
      in the counts of L. monocytogenes Scott A in fresh cheese was recorded after 3
      min at 400 MPa and 12 degrees C, whereas 18 min under the same conditions was
      required to obtain a 1-log reduction in ripe cheese. Dry matter values were
      48.96% for fresh cheese and 58.79% for ripe cheese, and water activity (aw)
      values were 0.983 and 0.922, respectively. In dehydrated fresh cheese (58.20% dry
      matter) in which 5% NaCl was added to achieve a 0.904 aw value, L. monocytogenes
      Scott A counts were lowered by only 0.4 log after treatment for 10 min at 400
      MPa. On the other hand, in a 60:40 mixture of ripe cheese:distilled water with a
      0.976 aw value, the reduction under the same conditions was 3.9 log. Within the
      aw range of 0.945 to 0.965, L. monocytogenes Scott A barotolerance was
      significantly higher in fresh cheese than in ripe cheese for equivalent aw
      values. Carbohydrate content was higher in fresh cheese than in ripe cheese. The
      addition of lactose at a concentration of 5 mg/g to an 85:15 mixture of ripe
      cheese:distilled water did not influence L. monocytogenes Scott A barotolerance
      during treatment for 10 min at 400 MPa. Galactose at a concentration of 5 mg/g
      had a protective effect during high-pressure treatment, and glucose at a
      concentration of 5 mg/g favored L. monocytogenes Scott A survival during
      refrigerated storage of pressurized samples at 8 degrees C for 5 days.

PMID- 16786854
TI  - Deoxynivalenol and satratoxin G potentiate proinflammatory cytokine and
      macrophage inhibitory protein 2 induction by Listeria and Salmonella in the
      macrophage.
AB  - Health risks from microbial pathogens and toxins encountered in food and the
      environment continue to be of worldwide concern. The purpose of this research was
      to test the hypothesis that trichothecene mycotoxins amplify inflammatory
      responses to foodborne bacterial pathogens. We assessed the capacity of
      deoxynivalenol (DON) and satratoxin G (SG) to potentiate chemokine and
      proinflammatory cytokine production in RAW 264.7 murine macrophages induced by
      Listeria monocytogenes and Salmonella Typhimurium. When macrophage cultures were
      incubated with killed irradiated suspensions of the pathogens for 24 h, the
      minimum Listeria concentrations for induction of macrophage inhibitory protein 2
      (MIP-2), interleukin-1beta (IL-beta), IL-6, and tumor necrosis factor alpha (TNF
      alpha) were 0.01, 0.01, 1.0, and 1.0 microg/ml (P < 0.05) and the minimum
      Salmonella concentrations were 0.01, 0.01, 0.1, and 0.1 microg/ml, respectively
      (P < 0.05). Induction of all four mediators by both pathogens was potentiated by
      DON (at 100 and 250 ng/ml); observed responses were significantly higher than
      predicted additive responses (P < 0.05). SG (at 2 and 5 ng/ml) also significantly
      amplified induction of IL-1beta and TNF-alpha (P < 0.05) by both Listeria and
      Salmonella. These results indicate that DON encountered in Fusarium-contaminated
      food and SG from Stachybotrys-contaminated indoor environments could magnify
      innate inflammatory responses to foodborne bacterial pathogens.

PMID- 16786855
TI  - Modeling the level of contamination of Staphylococcus aureus in ready-to-eat
      kimbab in Korea.
AB  - The risk of Staphylococcus aureus in ready-to-eat kimbab (rice rolled in laver)
      sold in Korea was evaluated by a mathematical modeling approach. Four nodes were
      constructed from preparation at retail to consumption. A predictive microbial
      growth model and survey data were combined with probabilistic modeling to
      simulate the level of S. aureus in a single kimbab at the time of consumption. We
      estimated the mean level of S. aureus to be 2.92 log CFU/g for a typical kimbab
      (150 to 200 g each) at the time of consumption. Our model also showed that 29.73%
      of the kimbabs had > or = 100,000 S. aureus CFU/g, which poses some risk of
      illness, since some level of enterotoxin would be expected from toxigenic
      strains. However, because of the lack of dose-response models for staphylococcal
      enterotoxin, the final level of S. aureus in the kimbabs could not be used to
      estimate how many people would become ill from eating them. Correlation
      sensitivity results showed that consumer eating patterns and initial
      contamination levels at retail stores were the most significant risk factors for
      illness and that temperature control under 10 degrees C was a critical control
      point in kimbab retail establishments to prevent the growth of S. aureus.

PMID- 16786856
TI  - Rapid detection of enterotoxigenic clostridium perfringens by real-time
      fluorescence resonance energy transfer PCR.
AB  - Clostridium perfringens is one of the etiologic agents of gas gangrene that can
      occur when a wound is contaminated with soil. Type A C. perfringens can cause
      foodborne and nonfoodborne gastrointestinal illnesses due to an enterotoxin (CPE)
      produced by some strains during sporulation. We developed a quantitative real
      time PCR assay based on fluorescence resonance energy transfer hybridization
      chemistry that targets the C. perfringens-specific phospholipase C (plc) gene and
      the enterotoxigenic gene (cpe) with the LightCycler and the Ruggedized Advanced
      Pathogen Identification Device (R.A.P.I.D.). The assay can detect as few as 20
      copies of target sequences per PCR. The total assay time, from extraction to PCR
      analysis, is 90 min. This assay is rapid, sensitive, and specific and will allow
      direct detection of C. perfringens in water, food, and stool samples. It should
      prove helpful in investigating foodborne illnesses due to C. perfringens and can
      be used as a tool to ensure the safety of food and water supplies.

PMID- 16786857
TI  - Microbial evolution during storage of seasoned olives prepared with organic acids
      with potassium sorbate, sodium benzoate, and ozone used as preservatives.
AB  - The effect of potassium sorbate, sodium benzoate, and ozone in combination with
      citric, lactic, and acetic acids on the microbial population of seasoned table
      olives of the olive 'Alorena' cultivar was studied in both fresh (FF) and stored
      fruits (SF). The inactivation/growth curves were modeled and the biological
      parameters estimated, with yeast used as the target microorganism. Regardless of
      the acid added, potassium sorbate showed a general inactivation effect on yeasts
      in the products prepared from both FF and SE Sodium benzoate had a rapid
      inactivation effect with FF, but with SF, it was effective only in the presence
      of acetic acid. A strain of Issatchenkia occidentalis was found that was
      resistant to the combination of this preservative with citric or lactic acids. In
      FF, ozone showed an initial marked inhibition against yeasts, but later, yeasts
      were again able to grow. In SF, ozone was a strong inactivating agent when it
      replaced any of the traditional preservatives. Lactic acid bacteria were always
      absent in products prepared from FF, and apparently were not affected by the
      different preservative agents in those prepared from SF. The behavior of yeasts
      and lactic acid bacteria populations in commercial products were similar to those
      found in experimental treatments.

PMID- 16786858
TI  - Occurrence of aflatoxins, ochratoxin A, and fumonisins in retail foods in Japan.
AB  - We conducted a survey of aflatoxin B1, B2, G1, and G2, ochratoxin A, and
      fumonisin B1, B2, and B3 contamination in various foods on the retail market in
      Japan in 2004 and 2005. The mycotoxins were analyzed by high-performance liquid
      chromatography, liquid chromatography-mass spectrometry, or high-performance thin
      layer chromatography. Aflatoxins were detected in 10 of 21 peanut butter samples;
      the highest concentration of aflatoxin B1 was 2.59 microg/kg. Aflatoxin
      contamination was not found in corn products, corn, peanuts, buckwheat flour,
      dried buckwheat noodles, rice, or sesame oil. Ochratoxin A was detected in
      oatmeal, wheat flour, rye, buckwheat flour, green coffee beans, roasted coffee
      beans, raisins, beer, and wine but not in rice or corn products. Ochratoxin A
      concentrations in contaminated samples were below 0.8 microg/kg. Fumonisins were
      detected in popcorn, frozen corn, corn flakes, and corn grits. The highest
      concentrations of fumonisins B1, B2, and B3 in these samples were 354.0, 94.0,
      and 64.0 microg/kg, respectively.

PMID- 16786859
TI  - Occurrence of patulin in organic, conventional, and handcrafted apple juices
      marketed in Belgium.
AB  - The aim of this research was to compare the occurrence of patulin in a large
      group of organic, conventional, and handcrafted apple juices marketed in Belgium.
      An analytical procedure based on high-performance liquid chromatography with UV
      detection was validated and used to analyze 177 apple juice samples: 65 organic,
      90 conventional, and 22 handcrafted. Patulin was detected in 22 samples (12%),
      and quantification was possible in 10 (6%) of these samples. The patulin content
      was higher than the European legal limit of 50 microg/liter in two samples of
      organic apple juice. Although, the incidence of patulin in organic (12%),
      conventional (13%), and handcrafted (10%) apple juices was not significantly
      different (P = 0.863), the mean concentration of patulin in contaminated samples
      was significantly higher in organic (43.1 microg/liter) than in conventional
      (10.2 microg/liter) (P = 0.02) and handcrafted (10.5 microg/liter) (P = 0.037)
      apple juice. The highest patulin concentrations were found in the most expensive
      apple juices because of the higher price of organic apple juice. This relation
      was not observed when only conventional apple juices were analyzed.

PMID- 16786860
TI  - Scanning electron microscopy of Anisakis larvae following different treatments.
AB  - Ingestion of fish parasitized with Anisakis larvae can produce infestation and/or
      allergy in consumers. Technological and food processing treatments have been
      applied to parasitized fish in order to kill the larvae and avoid the
      infestation; however, their influence on allergenicity has not been studied. Four
      lots of hake (Merluccius merluccius) steaks artificially parasitized with
      Anisakis larvae were subjected to two storage chilling (5 degrees C +/- 1 degrees
      C) and freezing (-20 degrees C +/- 1 degrees C) treatments and two food
      processing treatments of heat (final temperature 86.3 degrees C) and microwave
      (final temperature 66.9 degrees C) and studied by scanning electron microscopy,
      environmental scanning electron microscopy (ESEM) (acid [pH = 2] and water
      preparations), and emission of fluorescence. Anisakis larvae were resistant to
      acid conditions, remaining alive after treatment. Larvae in the heat- and
      microwave-treated lots presented coagulated and disrupted zones in the cuticle
      with release of fluids. The cylindrical shape changed to a dehydrated appearance
      mainly observed by ESEM. Fluorescence was only noticeable in the frozen larvae.
      Larvae without apparent changes, together with dehydrated ones, were observed by
      ESEM in the frozen lot; nevertheless, no disruptions in the cuticle were
      perceptible. Further studies are needed in order to elucidate if the changes
      observed in the cuticle reduce the resistance of the parasites to the action of
      gastric enzymes in the gastrointestinal tract and to determine the release of
      allergens to the flesh by the live larvae during chilled storage of the fish.

PMID- 16786861
TI  - Alternative cutting methods to minimize transfer of nervous system tissue during
      steak preparation from bone-in short loins.
AB  - Fresh beef products, such as steaks, may become contaminated with potential
      specified risk materials (SRMs), such as central nervous system tissue, during
      the fabrication of bone-in loin subprimals. The objective of this study was to
      evaluate current and alternative cutting methods that could be used to minimize
      the transfer of nervous system tissue (NST) tissue during preparation of steaks
      from bone-in short loins. Bone-in short loins were cut according to three
      methods. (i) Cutting method I-The vertebral column bones were removed prior to
      cutting the loin into steaks from the medial (vertebral column) to lateral
      (flank) side. (ii) Cutting method II--The loin was cut into steaks from the
      vertebral column side to the flank side prior to removal of the vertebral column
      bones. (iii) Cutting method III--The loin was cut into steaks from the flank side
      to the vertebral column side prior to removal of the vertebral column bones.
      Results indicated that surface areas along the vertebral column cutting line had
      detectable (0.10 and 0.22% NST/100 cm2) and, thus, higher potential SRM
      contamination than resulting steak surfaces or the cutting blade. Overall, there
      were no detectable (<0.10% NST/100 cm2) differences in NST contamination of
      steaks produced by the three cutting methods. Immunohistochemical evaluation of
      areas on excised and ground steak surfaces indicated that regardless of cutting
      method, there was generally "no" to "moderate" staining, suggesting that
      detectable (0.137 to 0.201% NST) contamination from these samples was most likely
      due to peripheral nerve detection. These results imply that steaks may be cut
      from bone-in short loins prior to removal of the vertebral column bones without
      affecting the transfer of NST to resulting steaks at concentrations <0.10%
      NST/100 cm2.

PMID- 16786862
TI  - Preliminary study on health-related lipid components of bakery products.
AB  - The purpose of this study was to evaluate the presence of health-related lipid
      components, in particular trans fatty acids and sterol oxidation products, in
      four bakery products. Both types of components are known for their adverse
      biological effects, especially the increase of atherogenic risk, and therefore it
      is advisable to monitor their presence in food products. Trans fatty acids were
      determined by silver-ion thin-layer chromatography-gas chromatography, whereas
      sterol oxidation was assessed by gas chromatography and gas chromatography-mass
      spectrometry determination of 7-keto derivatives (tracers of sterol oxidation).
      The amount of trans fatty acids (0.02 to 3.13 g/100 g of product), sterols (34.9
      to 128.3 mg/100 g of product), and 7-keto derivatives of sterols (1.88 to 3.14
      mg/kg of product) varied considerably among samples. The supply of phytosterols
      (22.5 to 64.0 mg/100 g of product) was not significant, and the extent of
      oxidation of most phytosterols to its corresponding 7-keto derivative was low
      (0.29 to 0.84%), except for that of brassicasterol (2.01 to 3.11%). The quality
      of ingredients and raw materials seems to have greatly influenced the fatty acid
      profile, stability, safety, and quality of the final product; these ingredients
      should be chosen with extreme care to decrease their potential negative health
      effects and to increase safety of these products.

PMID- 16786863
TI  - Relationship between total mercury concentration and fish size in two pelagic
      fish species: implications for consumer health.
AB  - Total mercury concentrations were determined in different size classes of two
      pelagic fish species of great commercial importance, horse mackerel (Trachurus
      trachurus) and Mediterranean horse mackerel (Trachurus mediterraneus), to
      evaluate the relationship between total mercury concentration and fish size and
      to determine whether any differences might affect the quantitative assessment of
      mercury exposure for consumers. Mercury concentrations in horse mackerel and in
      Mediterranean horse mackerel were between 0.16 and 2.41 microg g(-1) of weight
      wet (mean, 0.68 microg g(-1)) and between 0.09 and 1.62 microg g(-1) (mean, 0.51
      microg g(-1)), respectively. The regression curves revealed a significant
      relationship between mercury concentration and fish size (length and weight) for
      both species. Concentrations exceeding the proposed limit for human consumption
      were observed in 33.3% of the samples of both species and were associated with
      larger specimens. The consumption of the larger specimens could lead to an
      increase in mercury exposure for consumers. Estimated weekly intakes, calculated
      on the basis of concentrations relative to each size class, revealed a high
      exposure associated with the consumption of fish larger than 30 cm (horse
      mackerel, 11.63 to 20.16 microg/kg of body weight; Mediterranean horse mackerel,
      5.86 to 13.55 microg/kg of body weight). An understanding of the factors leading
      to an increase in mercury exposure can help consumers make informed decisions
      about eating fish.

PMID- 16786864
TI  - An electrochemical bioassay for dichlorvos analysis in durum wheat samples.
AB  - The use of an acetylcholinesterase inhibition assay for the detection of
      dichlorvos in durum wheat samples by a simplified extraction procedure is
      reported. After an incubation step, the residual activity was determined with an
      amperometric biosensor using a portable potentiostat. The use of electric eel and
      recombinant acetylcholinesterase was compared. The effect of the matrix extract
      was evaluated by using various sample:solvent ratios, 1:2.5, 1:5, 1:10, and 1:20.
      The optimal extraction ratio, considering the electrochemical interferences and
      the effect on enzyme activity and bioavailability of the pesticide, was 1:10.
      Calibrations were performed in buffer and durum wheat extract. The calculated
      detection limits in buffer solution were 10 ng/ ml and 0.045 ng/ml for electric
      eel and recombinant acetylcholinesterase, respectively, whereas operating in the
      matrix extract they increased up to 45 ng/ml and 0.07 ng/ml, corresponding to
      0.45 mg/kg (extraction ratio 1:10) and 0.07 mg/kg in samples. These
      characteristics allowed the detection of contaminated samples at the maximum
      residue limit, which is 2 mg/kg and well below. Fortified samples of durum wheat
      were obtained with both dichlorvos and the commercial product Didivane, which
      contains dichlorvos as an active molecule. At all the tested levels, the
      occurrence of contaminant was detected with an average recovery of 75%. The total
      assay time, including the extraction step, was 30 min. Because several
      extractions as well as most of the assay steps can be run simultaneously, the
      throughput for one operator is 12 determinations per hour.

PMID- 16786865
TI  - Food safety perceptions and behaviors of Kentucky consumers.
AB  - In several areas, Kentuckians practice more risky health behaviors than most of
      the rest of the nation. The Health Belief Model states that individuals with
      lower perceived risks practice less healthy behaviors. This study sought to
      determine if this was true for food safety by assessing food safety perceptions
      and behaviors of Kentucky consumers. Data were collected through a telephone
      questionnaire based on a survey by the U.S. Food and Drug Administration; 728
      respondents participated. Food safety perceptions were analyzed by examining
      participants' responses to confidence in the safety of the food supply,
      perception of likelihood of people becoming sick because of foodborne illness,
      and perception of where food safety problems are most likely to occur.
      Significant differences were found in food safety perceptions for age, gender,
      household income, education, and employment in the food industry. Analysis of
      food safety behaviors revealed differences in food handling behaviors for gender,
      education level, household income, race, and households with a member aged 65
      years or older. Significant relationships were found between respondents' food
      safety perceptions and behaviors. In general, Kentucky consumers who perceived
      higher risks exhibited safer food handling behaviors. Strategies to increase the
      understanding of real and perceived food safety risks in the home combined with
      strategies that target specific demographic groups may be the most effective
      approach to improve food handling practices. A better understanding of consumers'
      food safety risk perceptions and behaviors could lead to more effective food
      safety education materials and messages.

PMID- 16786866
TI  - PCR identification of Salmonella: potential contamination sources from production
      and postharvest handling of cantaloupes.
AB  - Salmonella is one of the most frequently reported etiological agents in outbreaks
      of foodborne diseases associated with the consumption of cantaloupes. Sensitive
      and reliable methods for detecting and identifying foodborne microorganisms are
      needed. The PCR can be used to amplify specific DNA fragments and thus to detect
      and identify pathogenic bacteria. In this study, a PCR method was used to
      evaluate the incidence of Salmonella at cantaloupe production, harvest, and
      packaging steps, and the results were compared with those of the standard method
      for detection of Salmonella in foods (Mexican NOM-114-SSA1-1994). Salmonella was
      detected by both standard and PCR methods in 23.5% of the irrigation water
      samples but only by the PCR method in 9.1% of the groundwater samples, 4.8% of
      the chlorinated water samples, 16.7% of samples from the hands of packing
      workers, 20.6% of samples from the packed cantaloupes, and 25.7% of samples from
      the in-field cantaloupes. With the standard method, Salmonella was found in 8.3%
      of the crop soil samples. Statistical analysis indicated a significant difference
      in sensitivity (P < 0.05) between the two methods; the PCR method was 4.3 times
      more sensitive than the standard method. Salmonella was found at seven of the
      eight pointsevaluated during the production and postharvest handling of
      cantaloupe melons.

PMID- 16786867
TI  - Effect of refrigeration on in vitro penetration of Salmonella enteritidis through
      the egg yolk membrane.
AB  - Internally contaminated eggs have been implicated as leading sources of
      transmission of Salmonella Enteritidis (SE) to humans. Although SE is not often
      deposited inside the nutrient-rich yolks of naturally contaminated eggs,
      penetration through the vitelline membrane to reach the yolk contents could
      result in rapid bacterial multiplication. In previous studies, such penetration
      has been observed occasionally at warm temperatures during experiments with in
      vitro egg contamination models. The present study was conducted to determine
      whether refrigeration affects the frequency of in vitro SE penetration of the egg
      yolk membrane. After inoculation of small numbers of SE onto the outside of the
      vitelline membranes of intact yolks, immediate refrigeration of contaminated
      samples prevented the penetration of SE into the egg yolk contents during 24 h of
      storage. However, SE penetrated inside the yolk contents in 4% of contaminated
      egg samples refrigerated after 2 h of storage at 30 degrees C, 15% of samples
      refrigerated after 6 h of storage at 30 degrees C, and 40% of samples stored at
      30 degrees C for 24 h (48 samples per treatment group). These results highlight
      the value of prompt refrigeration for restricting the opportunities for SE to
      multiply to high numbers inside the yolks of contaminated eggs.

PMID- 16786868
TI  - Effect of gamma or beta radiation on Salmonella DT 104 in ground pork.
AB  - Mixtures of six Salmonella Typhimurium DT 104 strains were inoculated into three
      ground pork products to determine the effect of fat content on the radiation
      resistance of Salmonella DT 104. The ground pork products were 90% lean, 50:50
      fat:lean, and 100% fat. Inoculated products were irradiated using a gamma
      radiation source in a self-contained 137Cesium irradiator or a 10 MeV accelerator
      producing electrons (e-beam). The radiation D10-values (dose required for a 90%
      inactivation of viable CFU) for Salmonella DT 104 inoculated into 90% lean ground
      pork, 50:50 fat/lean ground pork, and 100% pork fat and subjected to beta
      radiation were 0.42 kGy, 0.43 kGy, and 0.43 kGy, respectively. The corresponding
      radiation D10-values for Salmonella DT 104 subject to gamma radiation were 0.56,
      0.62, and 0.62 kGy, respectively. There was no statistical significant difference
      (P = 0.3) in radiation D10-values for Salmonella in the three products subject to
      either radiation treatment. Therefore, fat content had no effect. There was a
      significant difference (P = 0.001) between the radiation D10-values obtained with
      the two radiation sources. The radiation D10-values were within the reported
      range for irradiation destruction of Salmonella contaminated raw meat products.

PMID- 16786869
TI  - Gamma radiation sensitivity of Enterobacter sakazakii in dehydrated powdered
      infant formula.
AB  - The observed Enterobacter sakazakii D10-values for tryptic soy broth and
      dehydrated powdered infant formula were 0.27 +/- 0.05 and 0.76 +/- 0.08 kGy,
      respectively. A decrease of approximately 3 log in the dehydrated powdered infant
      formula was obtained by irradiation with 3.0 kGy or rehydration with hot water at
      80 degrees C. No recoverable bacteria were found in the powdered infant formula
      irradiated at 5.0 kGy and stored, either before or after rehydration. A radiation
      dose of up to 5.0 kGy had no marked effect on the sensory properties of the
      dehydrated powdered infant formula after rehydration and heating. Gamma radiation
      could potentially be used to inactivate E. sakazakii in dehydrated powdered
      infant formula; however, nutritional studies need to be conducted before the use
      of radiation can be recommended.

PMID- 16786870
TI  - Role of the rpoS gene in the survival of Vibrio parahaemolyticus in artificial
      seawater and fish homogenate.
AB  - Vibrio parahaemolyticus is a foodborne pathogen isolated from coastal waters of
      the United States and from a variety of seafood, including fish. Seawater
      represents a nutrient-limiting environment for V. parahaemolyticus. During its
      persistence in seawater, V. parahaemolyticus is exposed to a variety of
      environmental stresses, including hyperosmolarity, fluctuations in temperature,
      and cold stress. The alternate sigma factor of RNA polymerase, designated as
      (RpoS), encoded by the gene rpoS has been shown to play a major role in bacterial
      adaptive responses to adverse environmental conditions. The present study was
      undertaken to investigate the role of rpoS in the survival of V. parahaemolyticus
      in seawater and fish. A V. parahaemolyticus rpoS mutant was constructed by the
      insertion of a chloramphenicol acetyltransferase gene cassette within the rpoS
      gene, and the wild and mutant strains were assayed for their ability to survive
      in artificial seawater (ASW) at 6 and 1 degrees C and in fish homogenate at 4 and
      8 degrees C. The survival of the rpoS mutant of V. parahaemolyticus both in ASW
      and fish homogenate at either storage temperature was significantly (P < 0.05)
      lower than that of the wild strain. Further, the viability of V.
      parahaemolyticus, especially the mutant, was significantly reduced at lower
      storage temperatures of ASW and fish homogenate. Results of this study indicate
      that rpoS potentially plays an important role in the survival of V.
      parahaemolyticus under conditions of cold stress and hyperosmolarity.

PMID- 16786871
TI  - Pulsed-field gel electrophoresis typing of Listeria monocytogenes isolated in two
      Finnish fish farms.
AB  - The aim of this study was to find sources of Listeria monocytogenes contamination
      in fish products from a fish farm. The occurrence of L. monocytogenes also was
      compared in two freshwater fish farms with different types of fishponds. Samples
      collected from chilled rainbow trout (Oncorhynchus mykiss) and the slaughterhouse
      environment did not contain L. monocytogenes, but Listeria innocua was found in
      two samples from the slaughterhouses. Ten isolates of L. monocytogenes were
      discovered in sediment and water samples from farming tanks and earth ponds.
      Further characterization by serovar revealed the same serovar (1/2a) for all the
      isolates. Pulsed-field gel electrophoresis was used to divide the isolates into
      five different pulsotypes, three of which have been identified previously in fish
      products on the retail market. This finding supports the assumption that the
      primary production, and probably the raw fish, is a source of Listeria
      contamination in fish products. Some of the isolates were associated with a
      certain type of fishpond, indicating the need for hygienic analysis of the
      suitability of different types of farming ponds.

PMID- 16786872
TI  - Staphylococcal enterotoxin D production by Staphylococcus aureus FRI 100.
AB  - Staphylococcus aureus FRI 100 is commonly used as a control strain for
      staphylococcal enterotoxin A (SEA) assays. When FRI 100 was used in PCR-based
      enterotoxin detection methods, the strain gave a positive result for both SEA and
      staphylococcal enterotoxin D (SED). Production of SED was confirmed by testing
      concentrated and unconcentrated culture supernatants with the TECRA
      staphylococcal enterotoxin visual immunoassay. SED was detected after 24 h of
      growth in Trypticase soy broth. Primers were created to amplify the entire sed
      gene by PCR for subsequent sequencing. The sequenced gene showed high similarity
      to a previously sequenced sed gene. The SED-like gene in FRI 100 exhibited four
      point mutations and two deletions. Changes in the FRI 100 open reading frame
      altered the primary structure of the SED-like protein, allowing for coding of
      only the first 150 amino acids followed by a stop codon. Because the SED active
      site is at the proximal end, where there was no change in DNA sequence, we
      conclude FRI 100 produces a variant form of SED. It is necessary to note that,
      when using FRI 100 as an SEA control strain, it does produce a variant of the SED
      protein, which exhibits immunological activity, and the sed-like gene is detected
      by commonly used PCR primers. This phenomenon may be an important general
      consideration when using PCR to characterize strains of toxin-producing S.
      aureus. S. aureus enterotoxin-positive PCR results should be confirmed by
      immunological techniques.

PMID- 16786873
TI  - Location of bung bagging during beef slaughter influences the potential for
      spreading pathogen contamination on beef carcasses.
AB  - Preevisceration carcass washing prior to bung bagging during beef slaughter may
      allow pooling of wash water in the rectal area and consequent spread of potential
      pathogens. The objective of this study was to compare protocols for bung bagging
      after preevisceration washing with an alternative method for bung bagging before
      preevisceration washing for the potential to spread enterohemorrhagic Escherichia
      coli, E. coli O157:H7, and Salmonella on carcass surfaces. The study evaluated
      incidence rates of pathogens in preevisceration wash water (10 ml) samples (n =
      120) and on surface (100 cm2) sponge samples (n = 120) in the immediate bung
      region when bagging occurred before (prewash bagging) and after (postwash
      bagging) preevisceration washing. Surface sampling from postwash bagging yielded
      incidence rates of 58.3, 5, and 8.3%, whereas wash water sampling yielded 28.3,
      1.7, and 5% for enterohemorrhagic Escherichia coli, E. coli O157:H7, and
      Salmonella, respectively. Surface sampling from prewash bagging yielded incidence
      rates of 35, 1.7, and 0%, whereas wash water sampling yielded 18.3, 0, and 8.3%
      for enterohemorrhagic Escherichia coli, E. coli O157:H7, and Salmonella,
      respectively. Results of this research indicate that the rectal area is a
      significant source of pathogen contamination on carcasses and that wash water is
      an important mechanism for potential transfer of pathogen contamination from the
      rectal area. Results from this study suggest that bung bagging, as proposed in
      this study, before (prewash bagging) rather than after (postwash bagging)
      preevisceration washing was generally more effective in controlling pathogen
      contamination and potential spread from the rectal area of carcasses.

PMID- 16786874
TI  - Microbiological status of fresh beef cuts.
AB  - Fresh beef samples (n = 1,022) obtained from two processing plants in the Midwest
      (July to December 2003) were analyzed for levels of microbial populations (total
      aerobic plate count, total coliform count, and Escherichia coli count) and for
      the presence or absence of E. coli O157:H7 and Salmonella. A fresh beef cut
      sample was a 360-g composite of 6-g portions excised from the surface of 60
      individual representative cuts in a production lot. Samples of fresh beef cuts
      yielded levels of 4.0 to 6.2, 1.1 to 1.8, and 0.8 to 1.0 log CFU/g for total
      aerobic plate count, total coliform count, and E. coli count, respectively. There
      did not appear to be substantial differences or obvious trends in bacterial
      populations on different cuts. These data may be useful in establishing a
      baseline or a benchmark of microbiological levels of contamination of beef cuts.
      Mean incidence rates of E. coli O157:H7 and Salmonella on raw beef cuts were 0.3
      and 2.2%, respectively. Of the 1,022 samples analyzed, cuts testing positive for
      E. coli O157:H7 included top sirloin butt (0.9%) and butt, ball tip (2.1%) and
      for Salmonella included short loins (3.4%), strip loins (9.6%), rib eye roll
      (0.8%), shoulder clod (3.4%), and clod, top blade (1.8%). These data provide
      evidence of noticeable incidence of pathogens on whole muscle beef and raise the
      importance of such contamination on product that may be mechanically tenderized.
      Levels of total aerobic plate count, total coliform count, and E. coli count did
      not (P > or = 0.05) appear to be associated with the presence of E. coli O157:H7
      and Salmonella on fresh beef cuts. E. O157:H7 was exclusively isolated from cuts
      derived from the sirloin area of the carcass. Salmonella was exclusively isolated
      from cuts derived from the chuck, rib, and loin areas of the carcass. Results of
      this study suggest that contamination of beef cuts may be influenced by the
      region of the carcass from which they are derived.

PMID- 16786875
TI  - Antimicrobial properties of the chelating agent EDTA on Streptococcal bovine
      mastitis isolates.
AB  - To determine the efficacy of the chelating agent EDTA on microbial growth,
      separate cultures of two streptococcal bovine mastitis isolates, Streptococcus
      agalactiae and Streptococcus uberis, were exposed to known concentrations of
      EDTA. Bacterial cultures of 10(8) CFU/ml were exposed to concentrations of EDTA
      ranging from 30 to 100 mM in an in-vitro-milk environment. Multiple replications
      of cultures exposed to EDTA were plated during a two-hour time course. A
      concentration of 100 mM EDTA resulted in a 90% reduction of S. agalactiae and a
      99% reduction of S. uberis. Under these experimental conditions, EDTA treatments
      in cultures of both isolates exhibited from 1 to 2 log reductions suggesting that
      EDTA is a potentially effective antimicrobial against streptococcal isolates
      implicated in causing bovine mastitis.

PMID- 16786876
TI  - Aflatoxin B1 contamination in wheat grain samples collected from different
      geographical regions of India: A multicenter study.
AB  - In a multicenter study conducted by the Indian Council of Medical Research, 1,646
      samples of wheat grain collected from rural and urban areas of 10 states
      representing different geographical regions of India were analyzed for aflatoxin
      B1 (AFB1). AFB1 concentrations of > or = 5 microg kg(-1) were recorded in 40.3%
      of the samples, and concentrations above the Indian permissible regulatory limit
      of 30 microg kg(-1) were found in 16% of the samples. The proportion of samples
      with AFB1 concentrations above the Indian regulatory limit ranged from 1.7 to
      55.8% in different states, with the minimum in Haryana and the maximum in Orissa.
      The variation in wheat contamination among states seems to be mainly the result
      of unsatisfactory storage conditions. Median AFB1 concentrations of 11, 18, and
      32 microg kg(-1) were observed in samples from Uttar Pradesh, Assam, and Orissa,
      respectively; concentrations in other states were <5 microg kg(-1). The maximum
      AFB1 concentration of 606 microg kg(-1) was observed in a sample from the state
      of Uttar Pradesh. The calculated probable daily intakes of AFB1 through
      consumption of contaminated wheat for the population in some states were much
      higher than the suggested provisional maximum tolerable daily intake. Human
      health hazards associated with such AFB1 exposure over time cannot be ruled out.

PMID- 16786877
TI  - Green onions: potential mechanism for hepatitis A contamination.
AB  - The largest documented foodborne hepatitis A outbreak in U.S. history occurred in
      November 2003. The source of that outbreak was green onions from a farm in
      Mexico. Two biomarkers were used to determine ways in which hepatitis A virus
      (HAV) can contaminate onions. Fluorescent microspheres (1.0 to 10 microm) and HAV
      vaccine were placed on the soil and the surfaces of pot-grown onions and in the
      liquid medium of hydroponically cultivated onions. Reverse transcription PCR (RT
      PCR) was used to identify HAV RNA. Microspheres were found on the outside and
      inside of the pot-grown onions for up to 60 days. RT-PCR revealed HAV RNA from
      the vaccine in well-washed green onions. In the hydroponically grown onions,
      microspheres were found throughout the onion after only 1 day. RT-PCR also
      revealed HAV RNA inside the hydroponically grown onions. Both biomarkers support
      the hypothesis that HAV can contaminate the inside of the growing onion and can
      be taken up intracellularly through the roots. Once inside, the particles are
      impossible to remove by cleaning.

PMID- 16786878
TI  - Cold stress tolerance of Listeria monocytogenes: A review of molecular adaptive
      mechanisms and food safety implications.
AB  - The foodborne pathogen Listeria monocytogenes has many physiological adaptations
      that enable survival under a wide range of environmental conditions. The microbes
      overcome various types of stress, including the cold stress associated with low
      temperatures in food-production and storage environments. Cold stress adaptation
      mechanisms are therefore an important attribute of L. monocytogenes, enabling
      these food pathogens to survive and proliferate to reach minimal infectious
      levels on refrigerated foods. This phenomenon is a function of many molecular
      adaptation mechanisms. Therefore, an improved understanding of how cold stress is
      sensed and adaptation measures implemented by L. monocytogenes may facilitate the
      development of better ways of controlling these pathogens in food and related
      environments. Research over the past few years has highlighted some of the
      molecular aspects of cellular mechanisms behind cold stress adaptation in L.
      monocytogenes. This review provides an overview of the molecular and
      physiological constraints of cold stress and discusses the various cellular cold
      stress response mechanisms in L. monocytogenes, as well as their implications for
      food safety.

PMID- 16786879
TI  - Associatively activated representations of food events resemble food outcome
      expectancies more closely than they resemble food-based memories.
AB  - When Pavlovian stimuli activate representations of food, do these representations
      resemble memories of food consumed in the recent past or expectancies of food
      that is imminent? In Experiments 1A and 1B, this question was addressed by
      training pigeons on a symbolic matching-to-sample task involving different grains
      as memory cues or as expectancy cues for correct choices. Autoshaping trials
      involving these same grains were interspersed among matching-to-sample trials, as
      were test trials involving the substitution of autoshaping stimuli for cues in
      the matching-to-sample task. Control over choices transferred to autoshaping
      stimuli in both experiments, suggesting that associatively activated
      representations of food resemble both memories and expectancies. In Experiment 2,
      pigeons were trained on a symbolic matching-to-sample task in which food and no
      food memory cues (i.e., the samples) were juxtaposed with no-food and food
      expectancy cues. Subsequently, autoshaping stimuli, which activated
      representations of food and no food, were substituted for the samples. Choices by
      the pigeons indicated that associatively activated representations of food
      related events resemble expectancies more closely than they do memories.

PMID- 16786880
TI  - Spontaneous recovery from overexpectation.
AB  - In three Pavlovian magazine approach experiments, rats received conditioning of
      auditory and visual stimuli by pairing with a pellet. Then the stimuli received
      additional conditioning while presented in simultaneous compound and were tested
      either immediately or after a delay. The compound conditioning resulted in a
      decrement in responding to the individual stimuli (overexpectation). However,
      there was recovery of responding with the passage of time. These results suggest
      that the decrements produced by an overexpectation procedure share some
      properties with those produced by nonreinforcement.

PMID- 16786881
TI  - When more is less: extending training of the blocking association following
      compound training attenuates the blocking effect.
AB  - Three conditioned lick suppression experiments with rats were performed to assess
      the influence, following compound training of two stimuli (A and X) with the same
      outcome (AX-O trials), of extending training of the blocking association (i.e., A
      O) on responding to the target stimulus (X) at test. In Experiment 1, backward
      blocking was attenuated when the blocking association was extensively trained.
      Experiment 2 showed that forward blocking was also attenuated by extensive
      further training of the blocking association following the AX-O trials.
      Experiment 3 contrasted candidate explanations of the results of Experiments 1
      and 2 and demonstrated that these results are consistent with the framework of
      the extended comparator hypothesis (Denniston, Savastano, & Miller, 2001).

PMID- 16786882
TI  - Extinction of a saccharin-lithium association: assessment by consumption and
      taste reactivity.
AB  - Extinction of a conditioned palatability shift preceded extinction of conditioned
      taste avoidance whether rats were tested using a within-subjects design or a
      between-subjects design. In each of two experiments, consumption of 0.1%
      saccharin was paired with either 20 ml/kg of 0.15 M LiCl or equi-volume
      physiological saline on a single trial. In Experiment 1, on each of 10 extinction
      trials, rats were given a taste reactivity test immediately prior to a
      consumption test. In Experiment 2, half of the rats were extinguished by taste
      reactivity testing and half of the rats were extinguished by a consumption test
      on each of 10 extinction trials. In both experiments, the aversive reactions of
      gaping and passive dripping were extinguished in a single trial and the
      suppression of ingestive reactions was extinguished in 2 trials; however,
      extinction of taste avoidance required 4-5 trials. These results suggest that
      rats continue to avoid a lithium-paired flavor even when they do not have an
      aversion to the taste.

PMID- 16786883
TI  - Recovery of conditioned fear by a single postextinction shock: effect of
      similarity of shock contexts and of time following extinction.
AB  - Subjects in six experimental groups (n = 16 each) received one-trial passive
      avoidance (PA) training in which shock was delivered upon movement from a white
      wooden floor compartment to a black grid compartment. Then fear was extinguished
      (30 min) in the black compartment. After either 24 or 168 h, all the groups were
      treated in a room distinctively different from the training room. At each
      interval, one group received a shock in an apparatus similar to the conditioning
      box, another received a shock in a dissimilar apparatus, and another was placed
      in a neutral box. A PA test trial in the training apparatus indicated
      reinstatement of extinguished fear in all the groups given a postextinction shock
      except the 24-h dissimilar group. Control groups revealed that the extinction
      treatment was effective and that spontaneous recovery was not evident. The
      results were explained in terms of classical conditioning, stimulus
      generalization, and the broadening (flattening) of stimulus generalization
      gradients with time.

PMID- 16786884
TI  - Initial-link duration and acquisition of preference in concurrent chains.
AB  - Initial-link response allocation in concurrent chains becomes less extreme as the
      absolute duration of the initial links increases (Fantino, 1969). The present
      study asked whether initial-link duration affected how quickly response
      allocation reached asymptote (i.e., acquisition of preference). Six pigeons were
      trained on a concurrent-chains procedure in which the terminal links were fixed
      interval (FI) 8 sec FI 16 sec or FI 16 sec FI 8 sec and were reversed every 20
      sessions. Across conditions, all possible combinations of transitions between
      variable-interval (VI) 8-sec (short) and VI 24-sec (long) initial-link schedules
      were studied. Overall, the rate of acquisition was faster when the durations of
      the initial links preceding the reversal were short rather than long, and when
      the durations of the initial links following the reversal were long rather than
      short. By contrast, initial-link duration had no effect on acquisition or
      asymptotic measures of temporal control of terminal-link responding. These
      results support the core principle of delay-reduction theory (Fantino, 1969) that
      the impact of a conditioned reinforcer varies directly with initial-link
      duration, but also suggest that temporal learning during the terminal links
      proceeds independently ofinitial-link duration.

PMID- 16786885
TI  - Concurrent schedules of wheel-running reinforcement: choice between different
      durations of opportunity to run in rats.
AB  - How do animals choose between opportunities to run of different durations? Are
      longer durations preferred over shorter durations because they permit a greater
      number of revolutions? Are shorter durations preferred because they engender
      higher rates of running? Will longer durations be chosen because running is less
      constrained? The present study reports on three experiments that attempted to
      address these questions. In the first experiment, five male Wistar rats chose
      between 10-sec and 50-sec opportunities to run on modified concurrent variable
      interval (VI) schedules. Across conditions, the durations associated with the
      alternatives were reversed. Response, time, and reinforcer proportions did not
      vary from indifference. In a second experiment, eight female Long-Evans rats
      chose between opportunities to run of equal (30 sec) and unequal durations (10
      sec and 50 sec) on concurrent variable-ratio (VR) schedules. As in Experiment 1,
      between presentations of equal duration conditions, 10-sec and 50-sec durations
      were reversed. Results showed that response, time, and reinforcer proportions on
      an alternative did not vary with reinforcer duration. In a third experiment,
      using concurrent VR schedules, durations were systematically varied to decrease
      the shorter duration toward 0 sec. As the shorter duration decreased, response,
      time, and reinforcer proportions shifted toward the longer duration. In summary,
      differences in durations of opportunities to run did not affect choice behavior
      in a manner consistent with the assumption that a longer reinforcer is a larger
      reinforcer.

PMID- 16786886
TI  - Limits of dynamic object perception in pigeons: dynamic stimulus presentation
      does not enhance perception and discrimination of complex shape.
AB  - A go/no-go procedure was used to train pigeons to discriminate pictures of human
      faces differing only in shape, with either static images or movies of human faces
      dynamically rotating in depth. On the basis of experimental findings in humans
      and some earlier studies on three-dimensional object perception in pigeons, we
      expected dynamic stimulus presentation to support the pigeon's perception of the
      complex morphology of a human face. However, the performance of the subjects
      presented with movies was either worse than (AVI format movies) or did not differ
      from (uncompressed dynamic presentation) that of the subjects trained with a
      single or with multiple static images of the faces. Furthermore, generalization
      tests to other presentation conditions and to novel static views revealed no
      promoting effect of dynamic training. Except for the subjects trained on multiple
      static views, performance dropped to chance level with views outside the training
      range. These results are in contrast to some prior reports from the literature,
      since they suggest that pigeons, unlike humans, have difficulty using the
      additional structural information provided by the dynamic presentation and
      integrating the multiple views into a three-dimensional object.

PMID- 16786887
TI  - Modeling unidimensional categorization in monkeys.
AB  - The categorization performance of monkeys on a unidimensional perceptual
      categorization task was examined with reference to decision bound and exemplar
      theories of categorization. Three rhesus monkeys were presented with stimuli
      varying along a single dimension, the displacement of a target light from a
      fixation point. Left or right saccade responses were probabilistically reinforced
      according to one of three functions, two of which were nonmonotonic at one end of
      the stimulus space. The monkeys all showed a monotonic increase in response
      probability as a function of target light displacement in this region, consistent
      with decision bound theory. Fits of a single-boundary model (GRT, Ashby & Gott,
      1988) and two exemplar models--one using a probabilistic response function (GCM;
      Nosofsky, 1986), the other using a deterministic response function (DEM; Ashby &
      Maddox, 1993)--revealed overall support for the decision bound model. The results
      suggest that monkeys used a perceptual decision boundary to perform the task.

PMID- 16786888
TI  - Spatial pattern learning in the radial arm maze.
AB  - Rats experienced a spatial pattern of baited and unbaited arms in an eight-arm
      radial maze. The spatial pattern remained constant over trials, but the spatial
      locations that were baited varied unpredictably. Although there was no evidence
      of control by the spatial pattern during free choice training trials, the rats'
      ability to locate baited arms in forced choice test trials was superior to that
      of animals in a control condition for which maze arms were not baited in a
      consistent spatial pattern. This is consistent with the results of experiments
      showing that spatial choices by rats in a pole box maze are controlled by
      abstract spatial patterns.

PMID- 16786889
TI  - Let's thank the dentists.

PMID- 16786890
TI  - Court of appeals examines covenant-not-to-compete issues.

PMID- 16786891
TI  - The accusations fly!

PMID- 16786892
TI  - Top 10 lies dentists tell themselves.

PMID- 16786893
TI  - Maximize the dollar value of your dental scrap metal.

PMID- 16786894
TI  - Good communication can speed up your claims.

PMID- 16786895
TI  - Embezzlement: it can happen to you. Don't be a victim!

PMID- 16786896
TI  - Dr. Jane Grover: our ADA Second Vice President candidate. Interview by Dr. Jeff
      Johnston.

PMID- 16786897
TI  - Oral pathology quiz #17: incidental red and white lesion.

PMID- 16786899
TI  - Few support Howard on workchoices.

PMID- 16786898
TI  - What's in a name...?

PMID- 16786900
TI  - Your rights at work---nurses worth fighting for.

PMID- 16786901
TI  - Nurses keep the system safe.

PMID- 16786902
TI  - Federal budget--at a glance.

PMID- 16786903
TI  - After Larry.

PMID- 16786904
TI  - Eyes to the world.

PMID- 16786905
TI  - Attack on low paid workers' super. Regulation taskforce recommends cuts to super.

PMID- 16786906
TI  - Sodium and water retention in heart failure and diuretic therapy: basic
      mechanisms.
AB  - The pathophysiology of sodium and water retention in heart failure is
      characterized by a complex interplay of hemodynamic and neurohumoral factors.
      Relative arterial underfilling is an important signal that triggers heart failure
      related sodium and water retention. The response to perceived arterial
      underfilling is modulated by the level of neurohormonal activation, the degree of
      renal vasoconstriction, and the extent to which renal perfusion pressure is
      reduced. Sodium retention can also be exceeded by water retention, with the
      result being dilutional hyponatremia. Sodium and water retention in heart failure
      also function to dampen the natriuretic response to diuretic therapy. The
      attenuated response to diuretics in heart failure is both disease-specific and
      separately influenced by the rate and extent of diuretic absorption, the rapidity
      of diuretic tubular delivery, and diuretic-related hypertrophic structural
      changes that surface in the distal tubule.

PMID- 16786907
TI  - Acute decompensated heart failure: the cardiorenal syndrome.
AB  - The cardiorenal syndrome is not well understood, and a uniform definition is
      lacking. Worsening renal function as determined by a decline in creatinine
      clearance in patients with decompensated heart failure is an identifier of
      patients with this syndrome. Treatment is a challenge. Diuretic therapy is
      valuable in treating congestion but may worsen renal function. Patients with
      decompensated heart failure are often refractory to diuretics, in which case
      higher doses must be used or alternate methods explored to reduce salt and water.

PMID- 16786908
TI  - New approaches to detect and manage edema and renal insufficiency in heart
      failure.
AB  - Earlier detection of edema and renal insufficiency, before overt decompensation,
      is fundamental to further advances in altering the natural history of heart
      failure. Progress is being made in the earlier detection of these complications
      through the use of new devices that monitor for hemodynamic compromise and
      through monitoring of select cardiac and renal biomarkers. In addition, diuretic
      sparing approaches to heart failure management, novel drug classes, new devices,
      and nonpharmacologic therapies are emerging to reduce reliance on diuretic
      therapy and manage edema with less renal compromise.

PMID- 16786909
TI  - Vasopressin receptor antagonists: mechanisms of action and potential effects in
      heart failure.
AB  - Increased arginine vasopressin (AVP) secretion in heart failure may lead to
      vasoconstriction, left ventricular remodeling, and water retention-actions that
      promote afterload, preload, and hyponatremia and thereby cause disease
      progression. Interfering with AVP-mediated signaling pharmacologically may be
      beneficial in heart failure. Selective antagonism of the vasopressin 2 (V2)
      receptor may facilitate a safe diuresis and normalize low serum sodium levels, as
      demonstrated in preliminary clinical trials. Pure V2 antagonism, however, may
      stimulate AVP secretion and enhance V1a signaling, while pure V1a receptor
      antagonism may lead to unwanted V2 stimulation and secondary water retention and
      volume expansion. Combined V1a and V2 receptor antagonism could potentially prove
      advantageous as a therapy for heart failure by acting synergistically to
      facilitate diuresis and improve hemodynamics.

PMID- 16786910
TI  - The clinical effects of vasopressin receptor antagonists in heart failure.
AB  - The neurohormone arginine vasopressin (AVP) is a promising target in the
      treatment of heart failure because AVP promotes congestion and hyponatremia, each
      of which is associated with poor outcomes. Diuretics are standard therapy for
      heart failure, but they have several limitations, including worsening renal
      function and hyponatremia. Blocking AVP leads to effective aquaresis,
      improvements in hemodynamics and renal function parameters, weight loss, and
      normalization of serum sodium, without changes in blood pressure or heart rate.
      In placebo-controlled trials in the inpatient and outpatient setting, the AVP
      receptor antagonist tolvaptan reduced body weight and edema and normalized serum
      sodium in patients with heart failure.

PMID- 16786911
TI  - The life and trial of Dagmar Nelson--Part 1.
AB  - During the more desperate years of the Great Depression, a group of physicians
      brought an injunction proceeding against Dagmar Nelson and her employing hospital
      for illegally practicing medicine without a license. She administered general
      anesthesia and her employer knew it and supported her. It was a bizarre trial in
      that the arguments presented by both sides seem incongruous to our way of
      thinking today. The evidence presented at the trial echoed the predominant view
      at the time--the undisputed dominance of the male physician over the female
      nurse, who was portrayed, even by the defense, as only an extension of the
      surgeon who "has the power and therefore the responsibility" to control the
      surgery. Had she lost, anesthesia as a specialty of nursing would not exist. The
      method by which she won, however, has haunted us to this day. Part 2 of this 2
      part column on "The life and trial of Dagmar Nelson" is scheduled for publication
      in the August 2006 AANA Journal.

PMID- 16786912
TI  - Isoproterenol-induced elevated bispectral indexes while undergoing radiofrequency
      ablation: a case report.
AB  - The use of bispectral index (BIS) for monitoring neuronal function under general
      anesthesia has been expanding in practice. However, the meanings of the values
      are not always clear and have been shown to be altered by such drugs as ketamine,
      ephedrine, and physostigmine. Presented here is a case of increasing BIS in
      response to noradrenergic beta receptor stimulation via the administration of
      isoproterenol while under general anesthesia. The rise in BIS values appeared to
      have no correlation to the stimulation produced by the procedure. The patient
      reported no intraoperative recall despite BIS values in the high 70s. This case
      reinforces that BIS values require interpretation and can only be relevant to the
      circumstances of the individual case.

PMID- 16786913
TI  - Comparison of two approaches to brachial plexus anesthesia for proximal upper
      extremity surgery: interscalene and intersternocleidomastoid.
AB  - We conducted a prospective, randomized study to compare differences between
      groups of patients given a brachial plexus block using an interscalene (IS) or an
      intersternocleidomastoid (ISCM) approach. Specific variables analyzed included
      overall success rates, time to achieve sensory and motor anesthesia, time to
      place block, and incidence of side effects. For the study, 81 patients were
      randomized to receive a brachial plexus blockade using the IS or ISCM approach
      followed by general anesthesia for their surgical procedure. Intraoperative
      analgesics were controlled for in both groups. No differences in demographics,
      block success rate, pain scale scores, and analgesia duration were noted between
      groups. The ISCM group required less time to complete the block (7.08 +/- 2.9
      min) compared with the IS group (9.62 +/- 5.31 min) (P = .039), achieved a
      significantly higher rate of complete motor and sensory block at 30 minutes (P =
      .032), and had fewer side effects (P = .049). Based on our results, we found that
      using the ISCM approach to the brachial plexus resulted in a faster onset of
      anesthesia and a higher ratio of complete block at 30 minutes compared with the
      IS approach.

PMID- 16786914
TI  - Unintended subdural injection: a complication of epidural anesthesia--a case
      report.
AB  - Epidural anesthesia is practiced in virtually every clinical setting. Its safety
      and versatility have supported increasing use for more and varied therapies. In a
      healthy patient in whom near-complete left hemiparesis developed following a
      routine continuous epidural anesthetic for labor, subdural deposit of the local
      anesthetic was suspected. The following case and discussion may help illustrate
      the mechanism behind this complication and how it can be detected, treated, and,
      possibly, avoided.

PMID- 16786915
TI  - Assigning surgical cases with regional anesthetic blocks to anesthetists and
      operating rooms based on operating room efficiency.
AB  - The popularity of regional anesthesia blocks for both intraoperative anesthesia
      and postoperative pain management supports the inclusion of the administration of
      regional anesthesia into discussions about operating room (OR) efficiency. This
      article reviews the literature on OR efficiency with a focus on day-of-surgery
      decision making. Vignettes show regional anesthesia block placement is a variable
      that can affect the efficiency of use of OR time. Clinical examples highlight OR
      management issues and staff assignment decisions on the day of surgery. Regional
      anesthetic block placement can affect surgical schedules, and thus OR efficiency.
      When patient safety is unaffected, rearranging OR schedules on the day of surgery
      to place regional blocks, meet surgeon requests, or move up incision times should
      generally not be done if doing so results in otherwise unnecessary increases in
      overutilized OR time.

PMID- 16786916
TI  - Anesthesia concerns for children with tuberous sclerosis.
AB  - Tuberous sclerosis (TS) is a relatively rare, autosomal dominant syndrome that
      displays high genetic penetrance in affected families. It is identified by a
      classic triad of symptoms including epilepsy, skin lesions, and mental
      retardation. Tuberous sclerosis causes hamartomas in multiple organ systems,
      including the brain, skin, heart, kidneys, lungs, and liver. Awareness of the
      signs and symptoms and the organs involved is critical to provide safe and
      effective anesthesia care. We describe a 10-year-old girl with TS scheduled to
      receive a general anesthetic for laser treatment of facial angiofibromas. The
      patient had several coexisting maladies from TS, including hypertension, autism,
      seizure disorder, cardiac rhabdomyomas, developmental delay, and bilateral
      polycystic renal disease. The laser procedure was performed, and there were no
      surgical or anesthetic complications. However, the potential for complications
      due to TS remained high throughout the provision of anesthesia care. Increased
      knowledge of TS and diligence in anesthesia practice can greatly reduce these
      risks.

PMID- 16786917
TI  - Medical therapy to reduce perioperative cardiac complications.
AB  - Preoperative cardiac assessment has become an integral part of contemporary
      anesthesia practice. Simple clinical markers can identify high-risk patients, but
      the question of how to reduce cardiac complications among high-risk patients has
      been controversial. Good quality randomized controlled trials have showed that
      neither preoperative coronary revascularization nor the placement of pulmonary
      artery catheters reduces perioperative cardiac complications. On the other hand,
      there is increasing evidence that medical therapy offers myocardial protection
      and reduces perioperative cardiac complications. The data supporting these
      conclusions are reviewed in an evidence-based manner. At present, it is prudent
      to treat moderate- to high-risk patients undergoing elective surgery with beta
      blockers if possible. Because not all patients are candidates for beta-blocker
      therapy, data regarding the perioperative use of alternative medications to
      reduce perioperative cardiac complications have been explored and are reviewed.

PMID- 16786918
TI  - Update for nurse anesthetists. Eisenmenger syndrome: an anesthetic conundrum.
AB  - Eisenmenger syndrome is an insidious disease entity. This disease is
      characterized by an unrepaired congenital heart defect and left-to-right cardiac
      shunting. After many years of increased blood flow through the pulmonary system
      as a result of the shunting, damage to the pulmonary vessels occurs, culminating
      in severe pulmonary hypertension. The pulmonary hypertension eventually causes
      the cardiac shunt to reverse direction. The right-to-left shunt results in a very
      debilitated patient. There is no known medical cure for this disease; the only
      curative option is heart-lung transplantation or bilateral lung transplantation
      with repair of the patent heart defect. Because of the great strides in medical
      care, more patients with Eisenmenger syndrome require anesthesia. Maintaining the
      patient's systemic vascular resistance at the preoperative level is of paramount
      importance. Choosing the best anesthesia technique is difficult, at best.

PMID- 16786919
TI  - The tide has turned for specialists as trusts try to balance their books.

PMID- 16786920
TI  - Sobering message. Interview by Lynne Pearce.
AB  - As Northern Ireland's first alcohol liaison nurse, Gary Doherty has dramatically
      reduced the number of hospital admissions where misuse was an issue. His work has
      won him the RCN's 2006 Northern Ireland Nurse of the Year Award.

PMID- 16786921
TI  - Healthy on the inside. Interview by Carol Davis.
AB  - Prison inmates are at a disadvantage when it comes to health promotion and
      disease prevention. Nurses are trying to redress the balance.

PMID- 16786922
TI  - Postcode health care.
AB  - Health needs mapping can identify where people with particular conditions live-
      down to a postcode. Healthcare professionals can then target specific health
      promotion messages. Mapping exercises make use of techniques more commonly
      associated with retail marketing. Combining this information with hospital
      episode statistics allows people at risk of diseases to be identified. This works
      at the level of postcodes, which on average cover just 14 addresses.

PMID- 16786923
TI  - Home truths.

PMID- 16786924
TI  - All wound up.

PMID- 16786925
TI  - A very British service.

PMID- 16786926
TI  - Professional issues associated with the role of the research nurse.
AB  - This article presents the findings of two studies undertaken during 2002 and 2003
      that aimed to explore a range of professional issues facing research nurses. The
      results indicated that the position of research nurses is often complex because
      of a combination of contractual and accountability arrangements. This position
      can be intensified by feelings of isolation, a lack of professional support and
      limited specific educational opportunities. Experienced research nurses are often
      highly skilled in terms of their specialist clinical knowledge, and have a
      comprehensive understanding of all aspects of the research process, including
      methodological, ethical and practical issues.

PMID- 16786927
TI  - Critical practice in nursing care: analysis, action and reflexivity.
AB  - This article examines critical practice and its underlying principles: analysis,
      action and reflexivity. Critical analysis involves the examination of knowledge
      that underpins practice. Critical action requires nurses to assess their skills
      and identify potential gaps in need of professional development. Critical
      reflexivity is personal analysis that involves challenging personal beliefs and
      assumptions to improve professional and personal practice. Incorporating these
      aspects into nursing can benefit nursing practice.

PMID- 16786928
TI  - Promoting effective teaching and learning in the clinical setting.
AB  - This article explores the nature of teaching and learning in the clinical area.
      Many of the issues that mentors encounter in promoting a good learning
      environment and undertaking effective teaching are discussed.

PMID- 16786929
TI  - Nightlife emergency.

PMID- 16786930
TI  - Assessment of the patient with acute abdominal pain.
AB  - Abdominal pain has many causes, from simple to complex presentations. Patients
      with abdominal pain may have a number of physiological and psychological needs.
      Nurses have a key role to play in patient assessment, history taking and
      management.

PMID- 16786931
TI  - Art and soul.

PMID- 16786932
TI  - Rights for equals.

PMID- 16786933
TI  - A professional friend.

PMID- 16786934
TI  - The case: Bone disease in sickle cell anemia.

PMID- 16786935
TI  - Retrieving tendons.

PMID- 16786936
TI  - On the attainment of board certification.

PMID- 16786937
TI  - Accuracy of intra-articular injection of the glenohumeral joint: a cadaveric
      study.

PMID- 16786938
TI  - An ounce of prevention.

PMID- 16786939
TI  - Single incision arthroscopic ACL reconstruction in skeletally immature patients
      with direct visualization of the femoral and tibial physes.

PMID- 16786940
TI  - Butterfly-type splint immobilization to prevent thenar flap detachment in
      children.

PMID- 16786942
TI  - Scaphoid stress fracture: an unusual cause of wrist pain in a competitive diver.

PMID- 16786941
TI  - Pharmacokinetic considerations in the treatment of methicillin-resistant
      Staphylococcus aureus osteomyelitis.

PMID- 16786943
TI  - Venous thromboembolism following major orthopedic surgery: what is the risk after
      discharge?
AB  - Guidelines recommend thromboprophylaxis for at least 10 days to prevent venous
      thromboembolism in patients undergoing high-risk orthopedic surgery, such as
      total hip arthroplasty (THA) or total knee arthroplasty (TKA). Furthermore, the
      recently updated ACCP guidelines also recommend extending the duration of
      thromboprophylaxis for 28 to 35 days following THA or hip fracture surgery as the
      risk for venous thromboembolism persists for up to 3 months after surgery.
      Extended-duration thromboprophylaxis (up to 6 weeks) with low-molecular-weight
      heparin is significantly more effective in preventing venous thromboembolism in
      orthopedic surgery patients than the recommended practice of at least 10 days.
      Extended-duration thromboprophylaxis may require risk stratification to identify
      high-risk patients. Current risk-assessment models have limitations and are not
      specific to orthopedic surgery patients; therefore, improvements may facilitate
      the use of extended-duration thromboprophylaxis in high-risk patients, thereby
      reducing the burden of venous thromboembolism.

PMID- 16786944
TI  - Hip arthroscopy.
AB  - With adequate patient screening and attention to complications specific to the
      hip joint, hip arthroscopy can be performed safely and effectively. When used in
      appropriately selected patients, the reduced recovery and rehabilitation time is
      significant. In the past decade, the indications for hip arthroscopy have evolved
      to include a variety of pathologies, which has lead to a dramatic rise in its
      use.

PMID- 16786945
TI  - Painless reduction of acute anterior shoulder dislocations without anesthesia.
AB  - In 1938, Dr Henry Milch described a maneuver for the reduction of acute anterior
      shoulder dislocations consisting of shoulder abduction and external rotation with
      "pulsion" of the humeral head. Although many methods may be used to reduce the
      dislocated glenohumeral joint, the Milch technique is unique because of its
      gentle, effective, and relatively painless nature. This article studied the
      effectiveness of this technique on 76 consecutive acute anterior shoulder
      dislocations in 75 patients seen in our institution's two campuses over an 18
      month period. Twelve shoulders had concomitant fractures of the greater
      tuberosity. All 76 shoulders were reduced on the first attempt. No anesthesia was
      used, and no complications were reported from the reduction maneuver. The Milch
      method is an ideal first line treatment for all acute anterior shoulder
      dislocations including those associated with fracture of the greater tuberosity.

PMID- 16786946
TI  - Age and ACL reconstruction revisited.
AB  - To determine the age limitations for indicating ACL reconstructions in patients
      with functional instability, this article reviews the results of anterior
      cruciate ligament (ACL) reconstructions in 23 patients with an average age of 54
      years (range: 49-64 years). Patients were evaluated with the Lysholm and
      Gillquist knee questionairre, visual analog scale, satisfaction rating, physical
      examination, KT-1000 testing, and radiographs. Nineteen of the 23 patients were
      available for follow-up at an average of 24 months after the index procedure.
      Sixteen patients returned for physical examination and 3 agreed to telephone
      interviews. The mean Lysholm score was 92, visual analog score 0.5, satisfaction
      rating 100%, KT-1000 testing 2mm, range of motion 0 degrees to 135 degees.
      Sixteen of the 19 patients returned to acceptable activity levels. Fifteen
      patients had excellent or good results, while 4 patients had fair or poor
      results. Three of the 4 fair or poor results had significant moderate or severe
      knee arthrosis. Anterior cruciate ligament reconstruction with allograft in 49-64
      year-old patients with minimal arthrosis is a safe, minimally invasive procedure
      that allows for return to a desired level of activity.

PMID- 16786947
TI  - Supramalleolar tibial osteotomy secured with the Puddu plate.
AB  - Clinical indications for distal tibial osteotomies are rare and information on
      fixation techniques is limited. This article reviews a retrospective study of 4
      patients who underwent 5 distal tibial open-wedge osteotomies stabilized with a
      Puddu plate. All osteotomies healed within 3 months with no incidence of
      malunion, nonunion, or fixation failure and all deformities were adequately
      corrected. The Puddu plate (Arthrex Inc, Naples, Fla) provides secure fixation
      for open-wedge distal tibial osteotomies with accurate and reproducible results.

PMID- 16786948
TI  - Isolated anterior interosseous nerve palsy following sling immobilization.

PMID- 16786950
TI  - Parathyroid carcinoma metastasis presenting as a pathologic bone fracture.

PMID- 16786949
TI  - Dislocation of the first ray at the medial cuneonavicular joint in a football
      player.

PMID- 16786951
TI  - [Congenital heart disease in adults: necessity of specialized long-term follow
      up].

PMID- 16786952
TI  - [Tetralogy of Fallot: after the successful surgical correction...].
AB  - Tetralogy of Fallot is the most frequent cyanotic congenital heart disease
      (1/10000 births). The first complete corrections have been done in the fifties,
      and we now have long-term follow-up studies, revealing the most frequent
      arrhythmias and anatomic substrates compromising the long-term survival of these
      patients. The purpose of this article is to review some of the long-term
      complications of these patients, who, even if they have been completely
      corrected, will never be cured.

PMID- 16786953
TI  - [Transposition of the great arteries: long-term follow-up].
AB  - The management of transposition of the great arteries has changed importantly
      over the last decades. New techniques are employed for the diagnosis and surgical
      intervention has improved. This has lead to an increasing number of long-term
      survivors, who require specialised and focussed follow-up, depending on their
      type of surgical repair Mustard/Senning of arterial Switch. The long-term
      problems vary for each type of repair and require a specific approach,
      pharmacotherapy, catheter intervention or surgery. These complex sequellae
      implicate that transposition patients are never completely cured and probably
      will have a limited life span.

PMID- 16786954
TI  - [Univentricular hearts: long-term follow-up, complications and criteria for
      reintervention].
AB  - Univentricular hearts are complex and heterogeneous congenital heart defects.
      Treatment is surgical and comprises several palliative operations to permit long
      term survival in these patients. Late complications are frequent and need
      intensive treatments. This review article focuses on the main surgical
      interventions, complications, follow-up and reintervention criteria in patients
      with univentricular hearts.

PMID- 16786955
TI  - [Temporal trends in treatment of ST segment elevation myocardial infarction in
      Switzerland from 1997 to 2005].
AB  - From 1997 to 2005, 19461 patients admitted for acute coronary syndrome in 68
      hospitals in Switzerland were included in the AMIS Plus registry, of whom 11 543
      showed ST segment elevation or left bundle branch block on the ECG at admission.
      During this period, there was an important increase in the proportion of patients
      treated by primary percutaneous coronary intervention (8% to 74%), and a marked
      reduction in the use of thrombolysis (47% to 6%) and also in the proportion of
      patients who did not receive any reperfusion treatment (45% to 20%). Furthermore,
      there was a decrease in hospital mortality (12% to 7%). Main predictors of
      hospital mortality were withholding PCI and thrombolysis, advanced age and the
      presence of cardiogenic shock. Moreover, primary PCI was associated with lower
      hospital mortality when compared to thrombolysis.

PMID- 16786956
TI  - [Management of atrial flutter in 2006].
AB  - Typical or common atrial flutter is a frequent cardiac arrhythmia related to a
      macroreentrant circuit located entirely within the right atrium. Risks associated
      with this supraventricular arrhythmia include 1 to 1 conduction with extremely
      rapid ventricular rates, tachycardia-mediated cardiomyopathy and thromboembolic
      events. Treatment of choice of atrial flutter is radiofrequency catheter ablation
      of the cavo-tricuspid isthmus, and this form of treatment may be considered
      either during the first episode or at the time of the first recurrence of atrial
      flutter. Anticoagulant therapy is the rule in the presence of atrial flutter
      because this arrhythmia favors thromboembolic complications and because atrial
      flutter is frequently associated with atrial fibrillation.

PMID- 16786957
TI  - [Radiofrequency ablation in ventricular tachycardia: an alternative to implanted
      cardioverter defibrillator?].
AB  - Patients with ventricular tachycardia (VT) are subject to frequent recurrences
      despite antiarrhythmic drug therapy. Radiofrequency ablation is a useful
      alternative. Implantable defibrillators terminate episodes of VT but do not
      prevent them. The efficacy of catheter ablation depends on the cause and location
      of VT. There are two situations: VT in patients without identifiable structural
      heart disease or idiopathic VT and VT related to structural heart disease. After
      catheter ablation, idiopathic VT has a good prognosis and implantable
      defibrillators are usually not indicated. Scar-related VT are more difficult to
      treat with catheter ablation, but this technique is particularly useful for
      controlling frequent defibrillator shocks and incessant VT.

PMID- 16786958
TI  - [Therapeutic drug monitoring (TDM) of psychotropic drugs: a consensus guideline
      of the AGNP-TDM group].
AB  - In psychiatry, therapeutic drug monitoring (TDM) is an established procedure for
      most psychotropic drugs. However, as its use in everyday clinical practice is far
      from optimal, the AGNP-TDM group has worked out consensus guidelines to assist
      psychiatrists and laboratories involved in drug analysis. Based on a thorough
      analysis of available literature, 5 levels of recommendation were defined with
      regard to TDM of psychoactive drugs, from 1) (strongly recommended) to 5) (not
      recommended). A list of indications for TDM, alone or in combination with
      pharmacogenetic tests is presented. Instructions are given with regard to
      preparation of TDM, analytical procedures, reporting and interpretation of
      results and the use of information for patient treatment. Using the consensus
      guideline will help to ensure optimal clinical benefit of TDM.

PMID- 16786959
TI  - [The endocarditis of Mr. C].

PMID- 16786960
TI  - [A new step towards an influenza A H5N1 vaccine].

PMID- 16786961
TI  - [Therapeutic decision making].

PMID- 16786963
TI  - [Towards an updated set of International Health Regulations].

PMID- 16786962
TI  - [The Vatican, AIDS and condoms].

PMID- 16786964
TI  - [Clinicians and artificial organ specialists meet in Lausanne].

PMID- 16786965
TI  - [Oil and medicine: two common shortages].

PMID- 16786966
TI  - Medicare Part D and the challenge of a dynamic marketplace.

PMID- 16786967
TI  - Uninsurance among children eligible for the State Children's Health Insurance
      Program: results from a national survey.
AB  - Uninsurance among State Children's Health Insurance Program (SCHIP)--eligible
      children was examined using the 2001 National Survey of Children with Special
      Health Care Needs. Nationally, 6.1% of children (4.3 million) were eligible for
      SCHIP in 2000, and 35.6% (1.5 million) eligible children were uninsured. In
      addition to the variation across states in SCHIP eligibility and uninsurance, the
      study revealed a lower uninsurance rate in the 17 states that expanded Medicaid
      eligibility, compared with the 34 states with separate SCHIP programs that were
      implemented alone or in combination with Medicaid expansion. It was also revealed
      that the parents of SCHIP-eligible but uninsured children had limited knowledge
      of and experience with SCHIP.

PMID- 16786968
TI  - The National Guideline Clearinghouse.

PMID- 16786969
TI  - Managing the triptans.

PMID- 16786971
TI  - In the antitrust bull's eye: hospital mergers and professional associations.

PMID- 16786970
TI  - Effects of a polypharmacy edit and reduced quantity limits on the utilization of
      triptans and overall costs in an integrated health system.
AB  - On January 1, 2004, Intermountain Healthcare Health Plans implemented a
      polypharmacy edit and reduced the quantity limits of triptans to minimize the
      risks associated with triptan polypharmacy. The intervention covered one oral
      triptan brand per month and allowed one alternate formulation, limited monthly
      oral triptan quantities, and recommended use of prophylactic medication. During
      2003, the prescription count per quarter for triptans increased from 4,816 to
      5,359. The number of utilizing members increased from 2,659 to 2,781 over the
      course of the year. Total ingredient cost for fourth-quarter 2003 was dollar
      932,950. For first-quarter 2004, the prescription count was 4,131 (used by 2,423
      members) at a total ingredient cost of dollar 583,988. Fourth-quarter 2004
      utilization was 4,763 prescriptions, 2,719 members, and dollar 700,534 total
      ingredient cost. The total triptan spend was dollar 872,718 lower during 2004
      compared with 2003. Total medical claims remained constant over the two-year
      period for members who had a history of at least one triptan during that time.
      Educating members and health care professionals about the appropriate use of
      triptans can improve outcomes, and reevaluation of polypharmacy edits and
      quantity limits based on evolving clinical data improves the appropriate use of
      triptans.

PMID- 16786972
TI  - Do usual screening methods for prostate cancer reduce mortality?

PMID- 16786973
TI  - Disease constraints for utilization of the African buffalo (Syncerus caffer) on
      game ranches in Zambia.
AB  - Eco-tourism depending on wildlife is becoming increasingly profitable and
      landowners are beginning to favor game farming and ecotourism. In these areas,
      large-scale translocation of wildlife involves a diversity of species and large
      populations. The African buffalo (Syncerus caffer) is one of the major tourist
      attractions in Zambia. It accounts for 8.7% and 12.4% of the total animal species
      hunted in the Game Management Areas and the total hunting revenue earned in
      Zambia, respectively. It is ecologically an important animal species essential
      for the purpose of habitat control and facilitating the provision of suitable
      grazing pastures. However, the rearing of the African buffalo on game ranches has
      been hampered by its carrier state of the Southern Africa Terroritory (SAT)
      serotypes of foot and mouth disease virus (FMD). The African buffalo is also
      known to be a carrier of Theileria parva lawrencei, the causative agent of
      corridor disease (CD) that continues to have devastating effects on the livestock
      industry in Zambia. In addition, the importation of buffaloes from countries with
      populations endemic to bovine tuberculosis is highly restricted. Veterinary
      regulations in Zambia, strongly advocate against the translocation of buffaloes
      from protected areas to private ranches for disease control purposes thereby
      mounting a considerable constraint on the economic and ecological viability of
      the industry. It is hoped that this review will motivate the relevant government
      authorities in exploiting ways in which this animal species play a central role
      in eco-tourism.

PMID- 16786974
TI  - Ecology and epidemiology of anthrax in cattle and humans in Zambia.
AB  - Anthrax is endemic in Western and North-western Provinces of Zambia. The disease
      occurs throughout the year and impacts negatively on the economy of the livestock
      industry and public health in Zambia. During 1989-1995, there were 1626 suspected
      cases of anthrax in cattle in Western province and of these 51 were confirmed.
      There were 220 cases of human anthrax cases in 1990 alone and 248 cases during
      1991-1998 with 19.1% and 7.7% case fatality rates, respectively. Interplay of the
      ecology of affected areas and anthropogenic factors seem to trigger anthrax
      epidemics. Anthrax has drawn considerable attention in recent years due to its
      potential use as a biological weapon. In this paper, the history, current status
      and approaches towards the control of the disease in Zambia are discussed.
      Quarantine measures restrict trade of livestock and exchange of animals for
      draught power resulting in poor food security at household levels. Challenges of
      anthrax control are complex and comprise of socio-political, economical,
      environmental and cultural factors. Inadequate funding, lack of innovative
      disease control strategies and lack of cooperation from stakeholders are the
      major constraints to the control of the disease. It is hoped that the information
      provided here will stimulate continued awareness for the veterinary and medical
      authorities to maintain their surveillance and capabilities against the disease.
      This may lead to a culminating positive impact on livestock and human health in
      the southern African region.

PMID- 16786975
TI  - Experimental transmission of Bovine leukemia virus in cattle via rectal
      palpation.
AB  - We examined whether Bovine leukemia virus (BLV) was transmitted by rectal
      palpation using a common sleeve between a BLV-infected cow and BLV-negative
      steers. Three of four steers developed antibodies against BLV as determined by
      agar-gel immunodiffusion (AGID) test between 7 to 10 weeks after the first rectal
      palpation using common sleeves from BLV-infected cow. In the steers, BLV proviral
      DNA were detected by PCR 1 to 5 weeks earlier than detection of the antibodies by
      the AGID test. Our experiments demonstrated that rectal palpation is a potential
      cause of BLV spread in herds and that detection of BLV proviral DNA in cattle by
      PCR is useful screening test for early diagnosis of BLV infection.

PMID- 16786976
TI  - The promise of a community-based approach to managing severe malnutrition: A case
      study from Ethiopia.
AB  - BACKGROUND: Community-based therapeutic care (CTC) is a new strategy in the
      arsenal of techniques to manage complex nutritional emergencies in rural
      communities. The CTC approach uses a newly developed ready-to-use therapeutic
      food, Plumpynut, to rehabilitate severely malnourished children in their home
      communities. Emerging literature has suggested the CTC strategy yielded results
      that were superior to those of programs limited to therapeutic feeding centers,
      as measured by rates of coverage and numbers of children rehabilitated.
      OBJECTIVE: To compare the effectiveness of the CTC strategy in combination with
      conventional treatments for acute malnutrition. The expectation was that this
      program would support the growing consensus on the effectiveness of CTC
      strategies. METHODS: Data from monitoring the initial phase of program
      implementation were reviewed to ascertain program impact. The number of children
      participating and the outcome of their participation were assessed. RESULTS:
      Families became key participants in the rehabilitation of their children, and
      communities became strengthened through the mobilization of local networks and
      the improved knowledge base of local health workers. Recovery rates were
      comparable with international standards, and coverage far exceeded that of
      traditional center-based care. CONCLUSIONS: CTC is an important tool to
      effectively address nutritional emergencies and may be a valuable entry point for
      long-term development, since it fosters capacity building and improvement in
      local communities. CTC programs may eventually be viewed as the entry point for
      more sustained development-oriented interventions, thus helping make the
      transition from relief to development.

PMID- 16786977
TI  - Promotion of the feeding minds and fighting hunger initiative in selected rural
      schools in Andhra Pradesh, India.
AB  - BACKGROUND: Schoolchildren are good agents of change and need to be educated and
      sensitized to specific issues of hunger and malnutrition through a question-and
      answer process. Feeding Minds and Fighting Hunger (FMFH), a global project
      initiated by the Food and Agriculture Organization and partner organizations,
      attempts to help schoolchildren learn about these issues by introducing concepts
      in the prevention of hunger and malnutrition to teachers, and by facilitating
      transfer of knowledge to the children through a set of model lessons. OBJECTIVE:
      To test the feasibility of the FMFH approach to improve the nutrition knowledge
      of rural schoolchildren in three rural schools in Medak District of the South
      Indian state of Andhra Pradesh. METHODS: Participatory workshops for teachers
      were conducted to facilitate knowledge transfer to the children through
      interactive classroom teaching and other activities. The change in knowledge and
      thinking of children in the seventh and eighth grades was assessed by a ques-
      tionnaire administered before and after the intervention. The questionnaire also
      assessed, in part, the status of local food security based on the sources of
      different food items in the households. RESULTS: The responses to the
      questionnaire suggested that the children's knowledge of nutrients and their
      functions was not good initially but improved after the intervention. However,
      their understanding of the social factors responsible for hunger and malnutrition
      was fairly good prior to the intervention. Improvement in responses to the
      question of what should be done to combat malnutrition also occurred after
      intervention. The community had village-level food security for rice and maize
      but depended partially or fully on outside sources for pulses, fruits and
      vegetables, and animal products. CONCLUSIONS: The FMFH approach can be applied in
      rural schools where "the poorest of the poor" children can improve their
      understanding of balanced diets, better nutrition, the causes of malnutrition,
      and approaches to combat malnutrition.

PMID- 16786978
TI  - Child's gender and household food insecurity are associated with stunting among
      young Pakistani children residing in urban squatter settlements.
AB  - BACKGROUND: The nutritional status of children is a good indicator of the overall
      well-being of a society and reflects food security as well as existing health
      care and environmental conditions. In Pakistan, it is estimated that nearly 40%
      to 50% of children under the age of five are stunted. Due to greater economic
      opportunities available to the urban population as compared to the rural, it was
      believed that economic resources existed in poor urban Pakistani households but
      that the households lacked the skills and knowledge to translate their resources
      into good care and feeding practices. OBJECTIVE: This study aimed 1) to assess
      the prevalent care and feeding practices among children aged 6 to 18 months
      residing in the squatter settlements of Karachi and 2) to identify care and
      feeding practices, as well as any other underlying factors, associated with
      stunting. METHODS: A cross-sectional survey was conducted in eight settlements
      between October and December 2000. A total of 433 mothers of eligible children
      were interviewed with the use of structured questionnaires. Final analysis using
      multiple logistic regression was conducted on 399 mother-child pairs. RESULTS:
      Female children were nearly three times more likely to be stunted than male
      children. Households that were food insecure with hunger were also three times
      more likely than other households to have a stunted child. Lack of maternal
      formal schooling (adjusted prevalence odds ratio, 2.9; 95% confidence interval,
      1.4 to 3.8) and large household size (adjusted prevalence odds ratio, 1.7; 95%
      confidence interval, 1.0 to 3.8) were also associated with stunting. Even though
      certain care and feeding practices were significant at the univariate level, they
      were not significant in the final multivariate analysis and so were excluded from
      the final model. CONCLUSIONS: In households where food insecurity exists,
      knowledge of care practices may not be sufficient, and interventions such as food
      subsidies must precede or accompany educational efforts. Further follow-up is
      required to explore the effect of gender differences on child care.

PMID- 16786979
TI  - Women's empowerment and domestic violence: the role of sociocultural determinants
      in maternal and child undernutrition in tribal and rural communities in South
      India.
AB  - BACKGROUND: Moderate malnutrition continues to affect 46% of children under five
      years of age and 47% of rural women in India. Women's lack of empowerment is
      believed to be an important factor in the persistent prevalence of malnutrition.
      In India, women's empowerment often varies by community, with tribes sometimes
      being the most progressive. OBJECTIVE: To explore the relationship between
      women's empowerment, maternal nutritional status, and the nutritional status of
      their children aged 6 to 24 months in rural and tribal communities. METHODS: This
      study in rural Karnataka, India, included tribal and rural subjects and used both
      qualitative and quantitative methods of data collection. Structured interviews
      with mothers were performed and anthropometric measurements were obtained for 820
      mother-child pairs. The data were analyzed by multivariate and logistic
      regression. RESULTS: Some degree of malnutrition was seen in 83.5% of children
      and 72.4% of mothers in the sample. Biological variables explained most of the
      variance in nutritional status, followed by health-care seeking and women's
      empowerment variables; socioeconomic variables explained the least amount of
      variance. Women's empowerment variables were significantly associated with child
      nutrition and explained 5.6% of the variance in the sample. Maternal experience
      of psychological abuse and sexual coercion increased the risk of malnutrition in
      mothers and children. Domestic violence was experienced by 34% of mothers in the
      sample. CONCLUSIONS: In addition to the known investments needed to reduce
      malnutrition, improving women's nutrition, promoting gender equality, empowering
      women, and ending violence against women could further reduce the prevalence of
      malnutrition in this segment of the Indian population.

PMID- 16786980
TI  - Assessment of nutritional status of children under five years of age, pregnant
      women, and lactating women living in relief camps after the tsunami in Sri Lanka.
AB  - BACKGROUND: A strong earthquake that hit Aceh on December 26, 2004, triggered a
      powerful tsunami, resulting in an unprecedented catastrophe in Sri Lanka. The
      initial phase of the disaster was marked by limited access to food coupled with
      an inadequate supply of safe water and poor environmental hygiene and sanitation,
      all of which placed children at increased risk for undernutrition. OBJECTIVE: To
      assess the nutritional status of children under five years of age, pregnant
      women, and lactating women residing in 40 relief camps after the tsunami.
      METHODS: A cross-sectional, 30-cluster study was performed. Thirty children under
      five from each cluster (camp) and all pregnant and lactating women in selected
      camps were studied. Data were collected by interviews with the primary caregivers
      of the children, interviews with key informants in the camps, direct observation,
      and focus group discussions with mothers. Weight, height, or length was measured
      on children and pregnant women. Mid-upper-arm circumference of lactating women
      was measured. RESULTS: A total of 878 children were assessed, of whom 16.1%,
      20.2%, and 34.7% were wasted, stunted, and underweight, respectively. The
      prevalence of each indicator was higher in boys than in girls. During the 2 weeks
      before the survey, 69.5% of the children had acute respiratory tract infections
      and 17.9% had diarrhea. Although the general food distribution was well in place,
      the food supply lacked diversity, and 70.9% of the children did not get
      appropriate supplementary food. The prevalence of undernutrition among pregnant
      women (n = 168) was 37%. Thirty-one percent of lactating women (n = 97) were
      underweight, and 20% were overweight. CONCLUSIONS: The prevalence of both acute
      and chronic undernutrition among children in the camps is significantly higher
      than the national Sri Lankan average. There is a need to establish nutritional
      surveillance systems to monitor the nutritional status of displaced and
      nondisplaced children and mothers.

PMID- 16786981
TI  - Prevalence of challenging nutritional problems among adolescents in Sri Lanka.
AB  - BACKGROUND: Although 21% of the population of Sri Lanka consists of adolescents,
      studies of nutritional status among this group are limited. OBJECTIVE: To assess
      nutritional problems and dietary and activity patterns among adolescents in Sri
      Lanka. METHODS: A nationally representative cross-sectional study was conducted
      on 6,264 adolescents 10 to 15 years of age. All subjects were clinically examined
      for Bitot's spots, and their weights and heights were measured. The subjects were
      interviewed during regular class time. Hemoglobin concentration and dietary and
      activity patterns were assessed among a subsample (n = 787) of 1,521 adolescents.
      The World Health Organization age- and sex-specific references for body-mass
      index and height-for-age were used to estimate the prevalence of underweight and
      stunting, respectively. The International Obesity Task Force age- and sex
      specific reference for body-mass index was used to estimate the prevalence of
      overweight. Age-specific WHO-defined cut off points were used to estimate the
      prevalence of anemia. RESULTS: The prevalence rates of underweight, stunting, and
      overweight were 47.2%, 28.5%, and 2.2%, respectively. The prevalence rates of
      anemia and vitamin A deficiency were 11.1% and 0.4%, respectively. During the
      previous 6 months, 10.4% of the subjects had usually not eaten breakfast before
      going to school. During the week before the interview, 24.4% of the children had
      not consumed green leafy vegetables, 26.6% had not consumed fruit, 19.0% had not
      participated in physical activities, and 27.5% had watched television for more
      than 2 hours per day. CONCLUSIONS: The nutritional problems of adolescents aged
      10 to 15 years should be addressed through the schools. Specific policies should
      be developed in collaboration with the Ministry of Health and Education to
      control nutritional problems among adolescents.

PMID- 16786982
TI  - Evidence-based nutrition recommendations for the treatment and prevention of type
      2 diabetes and the metabolic syndrome.

PMID- 16786983
TI  - Agricultural biodiversity, nutrition, and health: making a difference to hunger
      and nutrition in the developing world.
AB  - BACKGROUND: In spite of the strides made globally in reducing hunger, the
      problems of micronutrient deficiencies and coexisting obesity and related
      cardiovascular and degenerative diseases constitute a formidable challenge for
      the future. Attempts to reverse this trend with single-nutrient intervention
      strategies have met with limited success, resulting in renewed calls for food
      based approaches. The deployment of agricultural biodiversity is an approach that
      entails greater use of local biodiversity to ensure dietary diversity. OBJECTIVE:
      To outline a new strategy proposed by the International Plant Genetic Resources
      Institute (IPGRI) that employs agricultural biodiversity as the primary resource
      for food security and health. METHODS: The authors carried out a meta-analysis to
      review and assemble existing information on the nutritional and healthful
      properties of traditional foods based on a diverse set of case studies and food
      composition and nutritional analysis studies. The methods highlight particular
      examples of foods where analysis of nutrient and non-nutrient composition reveals
      important traits to address the growing problems of malnutrition associated with
      the rise of chronic diseases. Finally, the authors analyze social, economic, and
      cultural changes that undermine the healthful components of traditional diets.
      RESULTS: Based on this multidisciplinary and comparative approach, the authors
      suggest a holistic food-based approach that combines research to assess and
      document nutritional and healthful properties of traditional foods, investigating
      options in which nutritionally valuable traditional foods can contribute to
      better livelihoods, and ways that awareness and promotional campaigns can
      identify healthful components of traditional diets that fit the needs of urban
      and market-oriented consumers. CONCLUSIONS: There is an urgent need for
      agricultural research centers, national agricultural research systems,
      universities, and community-based organizations to work together under a shared
      policy framework with the aim of developing a strong evidence base linking
      biodiversity, nutrition, and health. Although these initiatives are still
      ongoing, the gains realized in small-scale and local pilot efforts have
      encouraged IPGRI to work with local partners toward the implementation of scale
      up efforts in various regions.

PMID- 16786984
TI  - Child Nutrition Initiative in Israel and Palestine: Status of food security,
      micronutrient malnutrition, and behavioral change and communication programs.

PMID- 16786986
TI  - Introduction. Contraception is an extremely important consideration.

PMID- 16786985
TI  - Anthelmintic treatment improves the hemoglobin and serum ferritin concentrations
      of Tanzanian schoolchildren.

PMID- 16786987
TI  - The state of contraception care in the United States today: perspectives from the
      Planned Parenthood Federation of America.

PMID- 16786988
TI  - The costs of unintended pregnancy.

PMID- 16786989
TI  - A Managed Care Consensus statement on contraception and women's health.

PMID- 16786990
TI  - Hapten synthesis and development of polyclonal antibody-based multi-sulfonamide
      immunoassays.
AB  - This paper reports the synthesis of five sulfonamide derivatives, the production
      of broad-specificity polyclonal antibodies for immunoassay of sulfonamides, and
      the analysis of milk samples by developed assay. The three-step synthesis
      procedure reported in most of the literature was adopted and modified in this
      study. In the procedure, the purification of the intermediate was avoided and the
      time of synthesis was shortened from >20 to 6-9 h with improved yields. This
      method is generally applicable to the synthesis of haptens containing the common
      structure of sulfonamides. Three haptens were coupled to keyhole limpet
      hemocyanin, and polyclonal antibodies were obtained from rabbits immunized with
      these conjugates. Using the antibodies obtained, from one of these was developed
      an enzyme-linked immunosorbent assay (ELISA) based on the competition between
      free sulfonamides and the hapten-horseradish peroxidase (HRP) conjugates. The
      hapten-HRP conjugate giving the best competitive results and 11 structurally
      different sulfonamides showed 50% inhibition at concentrations of <100 ng mL(-1).
      After removal of the protein with acetone, milk samples were analyzed by ELISA
      directly; a matrix effect could be avoided when a 1:20 dilution with phosphate
      buffered saline was used, and 104-131% recoveries of spiked samples were
      obtained. The developed immunoassay is suitable to determine sulfisozole,
      sulfathiazole, sulfameter, sulfamethoxypyridazine, sulfapyridine, and
      sulfamethizole below the maximum residue limit in milk (100 ng mL(-1) of total
      sulfonamides) rapidly and reliably.

PMID- 16786991
TI  - Stable isotope and trace element profiling combined with classification models to
      differentiate geographic growing origin for three fruits: effects of subregion
      and variety.
AB  - Classifications of geographic growing origin of three fresh fruits combining
      elemental profiles with various modeling approaches were determined. Elemental
      analysis (Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, V, and Zn) of strawberry,
      blueberry, and pear samples was performed using inductively coupled plasma argon
      atomic emission spectrometer. Bulk stable carbon and nitrogen isotope analyses in
      pear were performed using mass spectrometry as an alternative fingerprinting
      technique. Each fruit, strawberry (Fragaria x ananassa), blueberry (Vaccinium
      caesariense/corymbosum), and pear (Pyrus communis), was analyzed from two growing
      regions: Oregon vs Mexico, Chile, and Argentina, respectively. Principal
      component analysis and canonical discriminant analysis were used for data
      visualization. The data were modeled using linear discriminant function,
      quadratic discriminant function, neural network, genetic neural network, and
      hierarchical tree models with successful classification ranging from 70 to 100%
      depending on commodity and model. Effects of Oregon subregional and variety
      classification were investigated with similar success rates.

PMID- 16786992
TI  - Quantitative and confirmatory analyses of malachite green and leucomalachite
      green residues in fish and shrimp.
AB  - Liquid chromatographic methods are presented for the quantitative and
      confirmatory determination of malachite green (MG) and leucomalachite green (LMG)
      for channel catfish, rainbow trout, tilapia, basa, Atlantic salmon, and tiger
      shrimp. Residues were extracted from tissues with ammonium acetate buffer and
      acetonitrile and isolated by partitioning into dichloromethane. LMG was
      quantitatively oxidized to the chromic MG with 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone. Extracts were analyzed for total MG by liquid chromatography with
      both visible detection (LC-VIS) at 618 nm for routine screening and ion trap mass
      spectrometry (LC-MSn) with no discharge-atmospheric pressure chemical ionization
      for residue confirmation. The method was validated in each species fortified with
      LMG at 1, 2, 4, and 10 ng/g (ppb), and average recoveries ranged from 85.9 to
      93.9%. Quantitative data were consistent for the two detection methods, with
      measured method detection limits of 1.0 ng/g for LC-VIS and 0.25 ng/g for LC-MSn.
      Incurred tissues from catfish, trout, tilapia, and salmon that had been treated
      with MG were also extracted and analyzed as part of this study.

PMID- 16786993
TI  - Selenium species in aqueous extracts of alfalfa sprouts by two-dimensional liquid
      chromatography coupled to inductively coupled plasma mass spectrometry and
      electrospray mass spectrometry detection.
AB  - The complementary use of two different liquid chromatographic mechanisms coupled
      to inductively coupled plasma mass spectrometry (ICP-MS) for selenium (Se)
      specific detection has permitted the screening of the most abundant Se-containing
      fractions in selenized alfalfa sprouts (Medicago sativa). Aqueous extracts of the
      sprouts were fractionated first by size exclusion chromatography (SEC) using a
      Superdex Peptide column and a mobile phase containing an ammonium acetate buffer
      (pH 7). Further purification of the individual SEC Se-containing fractions was
      carried out using two different chromatographic systems: a Shodex Ashaipack
      column, with a mixed mechanism of size exclusion and ion exchange, and a
      conventional reversed phase C8 using ion-pairing reagents. In both cases, the
      columns were coupled to an inductively coupled plasma mass spectrometer equipped
      with an octapole reaction system for Se specific detection. This system allowed
      the on-line monitoring of the most abundant Se isotopes (78Se, 80Se) by reducing
      the possible polytomic interferences affecting these ions by adding hydrogen (2
      mL min(-1)) to the octapole reaction cell. The results obtained by both
      separation mechanisms were highly comparable, revealing the presence of Se
      methionine and Se-methyl selenocysteine. Both compounds were then confirmed by
      analyzing the corresponding fractions by electrospray quadrupole-time-of-flight
      (ESI-Q-TOF) mass spectrometry. Finally, an additional Se-containing species
      showing Se isotope distribution was detected at a molecular ion m/z 239 in the
      ESI-Q-TOF. The collision-induced dissociation of the m/z 239 and 237 ions
      (corresponding to 80Se and 78Se isotopes, respectively) revealed the possible
      presence as well of a derivative of the Se-2-propenyl selenocysteine.

PMID- 16786994
TI  - Simultaneous determination of eight water-soluble vitamins in supplemented foods
      by liquid chromatography.
AB  - A fast, simple, and reliable method for the isolation and determination of the
      vitamins thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid,
      cyanocobalamin, and ascorbic acid in food samples is proposed. The most relevant
      advantages of the proposed method are the simultaneous determination of the eight
      more common vitamins in enriched food products and a reduction of the time
      required for quantitative extraction, because the method consists merely of the
      addition of a precipitation solution and centrifugation of the sample.
      Furthermore, this method saves a substantial amount of reagents as compared with
      official methods, and minimal sample manipulation is achieved due to the few
      steps required. The chromatographic separation is carried out on a reverse phase
      C18 column, and the vitamins are detected at different wavelengths by either
      fluorescence or UV-visible detection. The proposed method was applied to the
      determination of water-soluble vitamins in supplemented milk, infant nutrition
      products, and milk powder certified reference material (CRM 421, BCR) with
      recoveries ranging from 90 to 100%.

PMID- 16786995
TI  - Evaluation of a method for assaying sulfonamide antimicrobial residues in cheese:
      hot-water extraction and liquid chromatography-tandem mass spectrometry.
AB  - Several sulfonamide antimicrobials (SAAs) are largely used in veterinary
      medicine. A rapid, specific, and sensitive procedure for determining 12 SAAs in
      cheese is presented. The method is based on the matrix solid-phase dispersion
      technique followed by liquid chromatography (LC)-tandem mass spectrometry (MS)
      equipped with an electrospray ion source. Target compounds were extracted from
      Mozzarella, Asiago, Parmigiano, Emmenthal, and Camembert cheese samples by 6 mL
      of water modified with 10% methanol and heated at 120 degrees C. The addition of
      methanol to hot water served to improve remarkably extraction yields of the most
      lipophilic SAAs, that is, sulfadimethoxine and sulfaquinoxaline. After
      acidification and filtration, 100 microL of the aqueous extract was injected in
      the LC column. MS data acquisition was performed in the multireaction monitoring
      mode, selecting two precursor-to-product ion transitions for each target
      compound. Methanol-modified hot water appeared to be an efficient extractant,
      because absolute recovery ranged between 67 and 88%. Using sulfamoxole as
      surrogate analyte, recovery of the 12 analytes spiked in the five types of cheese
      considered at the 50 ng/g level ranged between 75 and 105% with RSD not higher
      than 11%. Statistical analysis of the mean recovery data showed that the
      extraction efficiency was not affected by the type of cheese analyzed. This
      result indicates this method could be applied to other cheese types not
      considered here. The accuracy of the method was determined at three spike levels,
      that is, 20, 50, and 100 ng/g, and varied between 73 and 102% with relative
      standard deviations ranging between 4 and 12%. On the basis of a signal-to-noise
      ratio of 10, limits of quantification were estimated to be <1 ng/g.

PMID- 16786996
TI  - Nondestructive determination of lignans and lignan glycosides in sesame seeds by
      near infrared reflectance spectroscopy.
AB  - Sesame (Sesamum indicum L.) contains abundant lignans including lipid-soluble
      lignans (sesamin and sesamolin) and water-soluble lignan glycosides (sesaminol
      triglucoside and sesaminol diglucoside) related to antioxidative activity. In
      this study, near infrared reflectance spectroscopy (NIRS) was used to develop a
      rapid and nondestructive method for the determination of lignan contents on
      intact sesame seeds. Ninety-three intact seeds were scanned in the reflectance
      mode of a scanning monochromator. This scanning procedure did not require the
      pulverization of samples, allowing each analysis to be completed within minutes.
      Reference values for lignan contents were obtained by high-performance liquid
      chromatography analysis. Calibration equations for lignans (sesamin and
      sesamolin) and lignan glycosides (sesaminol triglucoside and sesaminol
      diglucoside) contents were developed using modified partial least squares
      regression with internal cross-validation (n = 63). The equations obtained had
      low standard errors of cross-validation and moderate R2 (coefficient of
      determination in calibration). The prediction of an external validation set (n =
      30) showed significant correlation between reference values and NIRS predicted
      values based on the SEP (standard error of prediction), bias, and r2 (coefficient
      of determination in prediction). The models developed in this study had
      relatively higher values (more than 2.0) of SD/SEP(C) for all lignans and lignan
      glycosides except for sesaminol diglucoside, which had a minor amount, indicating
      good correlation between the reference and the NIRS estimate. The results showed
      that NIRS, a nondestructive screening method, could be used to rapidly determine
      lignan and lignan glycoside contents in the breeding programs for high quality
      sesame.

PMID- 16786997
TI  - Development of monoclonal antibodies against pirimiphos-methyl and their
      application to IC-ELISA.
AB  - To detect the organophosphorus (OP) pesticide pirimiphos-methyl in grain samples,
      a monoclonal antibody-based indirect competitive enzyme-linked immunosorbent
      assay (IC-ELISA) was developed and optimized. By the active esters method,
      pirimiphos-methyl hapten A was conjugated to keyhole limpet hemocyanin to be used
      as the immunogen for the production of monoclonal antibodies, and pirimiphos
      methyl hapten B was conjugated to ovalbumin to be used as coating antigen. By
      using the monoclonal antibody and the coating antigen, an IC-ELISA has been
      developed. Under the established optimized conditions, the IC-ELISA showed an
      IC50 of 4.2 ng/mL with a detection limit of 0.07 ng/mL. The IC-ELISA showed
      negligible cross-reactivity with other OP pesticides except with pirimiphos
      ethyl. Recoveries of pirimiphos-methyl from spiked grain samples ranged from 83
      to 96%.

PMID- 16786998
TI  - Antimutagenic and antioxidant properties of phenolic fractions from Andean purple
      corn (Zea mays L.).
AB  - The antimutagenic and antioxidant properties of various phenolic fractions
      obtained from Andean purple corn were examined by the Ames test and the DPPH
      antiradical assay. An anthocyanin-rich water fraction (WF) and an ethyl acetate
      fraction (EAF) showed a dose-dependent antimutagenic behavior against the food
      mutagen Trp-P-1 with IC50 values of 321.7 +/- 21.36 and 95.2 +/- 10.95 microg of
      chlorogenic acid equiv/plate, respectively, indicating that EAF was a more potent
      antimutagen. The antioxidant activities for WF and EAF were 1.019 +/- 0.05 and
      0.838 +/- 0.11 microg of Trolox equiv/mug of phenolics, respectively. Further
      fractionation of WF and EAF revealed an ethyl acetate subfraction, EA-IV, with
      high antimutagen potency that contained a quercetin derivative. The mechanism of
      antimutagenic action of the WF is predominantly a blocking effect on the S-9 Mix
      activation system of the mutagen, whereas for the EAF, it is a dual mechanism
      involving blocking of the S-9 Mix and a scavenging action on Trp-P-1
      electrophiles.

PMID- 16786999
TI  - Angiotensin I-converting enzyme inhibitory peptide derived from glycinin, the 11S
      globulin of soybean (Glycine max).
AB  - Angiotensin I-converting enzyme (ACE), a dipeptidyl carboxypeptidase, catalyzes
      the conversion of Angiotensin I to the potent vasoconstrictor Angiotensin II and
      plays an important physiological role in regulating blood pressure. Inhibitors of
      angiotensin 1-converting enzyme derived from food proteins are utilized for
      pharmaceuticals and physiologically functional foods. ACE inhibitory properties
      of different enzymatic hydrolysates of glycinin, the major storage protein of
      soybean, have been demonstrated. The IC50 value for the different enzyme digests
      ranges from 4.5 to 35 microg of N2. The Protease P hydrolysate contained the most
      potent suite of ACE inhibitory peptides. The ACE inhibitory activity of the
      Protease P hydrolysate after fractionation by RP-HPLC and ion-pair chromatography
      was ascribed to a single peptide. The peptide was homogeneous as evidenced by
      MALDI-TOF and identified to be a pentapeptide. The sequence was Val-Leu-Ile-Val
      Pro. This peptide was synthesized using solid-phase FMOC chemistry. The IC50 for
      ACE inhibition was 1.69 +/- 0.17 microM. The synthetic peptide was a potent
      competitive inhibitor of ACE with a Ki of 4.5 +/- 0.25 x 10(-6) M. This peptide
      was resistant to digestion by proteases of the gastrointestinal tract. The
      antihypertensive property of this peptide derived from glycinin might find
      importance in the development of therapeutic functional foods.

PMID- 16787000
TI  - Quantification of the polyphenols and triterpene acids in chinese hawthorn fruit
      by high-performance liquid chromatography.
AB  - The levels of seven polyphenols (epicatechin, procyanidin B2, procyanidin B5,
      procyanidin C1, hyperoside, isoquercitrin, and chlorogenic acid) and two
      triterpene acids (oleanolic acid and ursolic acid) in the matured fruits of
      Chinese hawthorn (Crataegus pinnatifida Bge. var. major N.E.Br.) were determined
      by high-performance liquid chromatography methods. The average contents of those
      constituents in 37 representative cultivars were 1405, 1505, 339, 684, 56, 41,
      234, 952, and 147 microg/g fresh weight (FW), respectively. A significant inverse
      correlation between the procyanidin contents and the latitude of the geographical
      origin of the cultivars was observed (r = 0.3851, P < 0.02). Correlation analysis
      of the levels of the nine compounds in the 37 cultivars yielded a strong
      correlation (P < 0.001) between the individual levels of the four procyanidins
      and the sum of the procyanidins level (r = 0.7413-0.9898) and between the
      flavonoids and the chlorogenic acid (r = 0.5383-0.9212). The changes in level of
      the nine compounds in the hawthorn fruit were evaluated during maturation using
      the Hebei Dajinxing cultivar. Sixty-one days after blossom, the polyphenol level
      reached the highest point and the sum of the contents was 1.36 g/100 g FW.

PMID- 16787001
TI  - Effects of ergot alkaloids on food preference and satiety in rabbits, as assessed
      with gene-knockout endophytes in perennial ryegrass (Lolium perenne).
AB  - Neotyphodium species are fungal endophytes best known for their protection of
      grass hosts and production of bioactive metabolites including ergot alkaloids.
      Perennial ryegrass-Neotyphodium sp. Lp1 symbiota that have altered ergot alkaloid
      profiles (resulting from knockouts in two different endophyte genes) were fed,
      along with controls, to rabbits to test the effects of ergot alkaloids on food
      preference and satiety. Interestingly, rabbits dramatically preferred plants that
      were endophyte-infected but free of ergot alkaloids over endophyte-free plants (P
      = 0.01). Accumulation of ergot alkaloids of the clavine class counteracted the
      added appeal of endophyte-infected plants. In satiety tests, consumption of
      ergovaline (the ultimate ergot pathway product in wild-type endophyte), but not
      of several other ergot alkaloids, during an initial meal had a negative effect on
      subsequent rabbit chow consumption (P < 0.05). The data indicate that clavines
      were sufficient to reduce the appeal of endophyte-infected grasses, whereas only
      ergovaline reduced appetite.

PMID- 16787002
TI  - Alpha-glucosidase inhibitory and antihyperglycemic effects of polyphenols in the
      fruit of Viburnum dilatatum Thunb.
AB  - Small crimson fruit of Viburnum dilatatum Thunb. (gamazumi), a wild deciduous low
      tree belonging to a family of Caprifoliaceae, has strong antioxidant activity,
      and cyanidin 3-sambubioside (C3S) and 5-caffeoyl quinic acid (5-CQA) are
      identified as active compounds. The freeze-dried powder of V. dilatatum fruit
      juice (CEV) was orally administered to streptozotocin-induced diabetic rats for 4
      weeks repeatedly. Consequently, the elevation of plasma glucose level after oral
      administration of 2 g/kg glucose was suppressed by the repeated administration of
      CEV. The action was dependent on the dose of CEV, and plasma glucose level in
      rats administered 500 mg/kg of CEV was decreased significantly from that in rats
      without CEV. Increase of insulin secretion was not found in rats with or without
      administration of CEV. It was expected that CEV had some effects on glucose
      uptake. In five compounds identified from V. dilatatum fruit, C3S and 5-CQA
      showed inhibitory activity on sucrase and maltase. Inhibitory activity of
      cyanidin 3-glucoside and cyanidin aglycon (Cy) was not found markedly, and so it
      was thought that the activity was a characteristic property in Cy diglycosides.
      Moreover, 5-CQA and C3S were main polyphenol in the fruit of V. dilatatum. These
      results suggest that V. dilatatum fruit has the alpha-glucosidase inhibitory
      activities and the antihyperglycemic action.

PMID- 16787004
TI  - Chemical composition of abaca (Musa textilis) leaf fibers used for manufacturing
      of high quality paper pulps.
AB  - The chemical composition of leaf fibers of abaca (Musa textilis), which are
      commonly used for high-quality paper pulp production, was thoroughly studied. The
      results revealed that the lignin content was 13.2% of the total fiber. The
      analysis of abaca fibers by pyrolysis coupled to gas chromatography-mass
      spectrometry (Py-GC/MS) released predominantly compounds arising from lignin and
      p-hydroxycinnamic acids, with high amounts of 4-vinylphenol. The latter compound
      was demonstrated to arise from p-coumaric acid by pyrolysis of abaca fibers in
      the presence of tetramethylammonium hydroxide, which released high amounts of p
      coumaric acid (as the methyl derivative). Products from p-hydroxyphenyl (H),
      guaiacyl (G), and syringyl (S) propanoid units, with a predominance of the latter
      (H:G:S molar ratio of 1.5:1:4.9), were also released after Py-GC/MS of abaca
      fibers. Sinapyl and coniferyl acetates, which are thought to be lignin monomer
      precursors, were also found in abaca. The extractives content of the abaca fiber
      (0.4%) was low, and the most predominant compounds were free sterols (24% of
      total extract) and fatty acids (24% of total extract). Additionally, significant
      amounts of steroid ketones (10%), triglycerides (6%), omega-hydroxyfatty acids
      (6%), monoglycerides (4%), fatty alcohols (4%), and a series of p-hydroxycinnamyl
      (p-coumaric and ferulic acids) esterified with long chain alcohols and omega
      hydroxyfatty acids were also found, together with minor amounts of steroid
      hydrocarbons, diglycerides, alpha-hydroxyfatty acids, sterol esters, and sterol
      glycosides.

PMID- 16787003
TI  - Antioxidant activity of Botryococcus braunii extract elucidated in vitro models.
AB  - Botryococcus braunii is a green colonial microalga that is used mainly for the
      production of hydrocarbons, exopolysaccharides, and carotenoids. In the present
      study, the antioxidant properties of acetone extracts of B. braunii were
      evaluated using in vitro model systems such as 1,1-diphenyl-2-picrylhydrazyl
      (DPPH), hydroxy radical scavenging, and lipid peroxidation in human low-density
      lipoprotein and rat tissues. Acetone extracts of B. braunii (equivalent to 10 ppm
      total carotenoid) exhibited 71 and 67% antioxidant activity in DPPH and hydroxyl
      radical scavenging model systems, respectively. Similarly, the extract also
      showed 72, 71, and 70% antioxidant activity in the liver, brain, and kidney of
      rats. Low-density lipoprotein oxidation induced by Cu2+ ions was also protected
      (22, 38, and 51%) by the algal extract in a dose-dependent manner (4, 6, and 8
      ppm levels of total carotenoid). Thiobarbituric acid reactive substances
      concentration in the blood, liver, and kidney of rats was also significantly
      decreased in B. braunii treated samples compared with those of control.
      Carotenoids (violaxanthin, astaxanthin, lutein, zeaxanthin, chlorophylls a and b,
      and alpha, beta-carotene) identified in the B. braunii acetone extract may be
      exhibiting antioxidant activity. Among the carotenoids, lutein represents more
      than 75% of the total carotenoids. B. braunii extract was shown to be effective
      for protecting biological systems against various oxidative stresses in vitro.
      This is the first report on the antioxidant properties of B. braunii.

PMID- 16787005
TI  - Plasticization of a protein-based film by glycerol: a spectroscopic, mechanical,
      and thermal study.
AB  - Kafirin, the seed storage protein of the cereal sorghum, is highly homologous
      with the maize storage protein zein. The effects of plasticisation of a kafirin
      film by glycerol in the absence of water were examined by a combination of
      spectroscopic (NMR and infrared), rheological, and calorimetric methods. The
      results suggest that at low glycerol levels the glycerol is absorbed onto and
      possibly into the protein. Increasing the level of glycerol increases the motion
      of the protein and changes the protein conformation. There are corresponding
      changes of the mechanical properties of protein films. At 40% (w/w) of glycerol,
      two glass transition temperatures were observed, one of which corresponded to the
      glass transition temperature of pure glycerol. This result indicates that at this
      level of plasticizer there are sufficient glycerol/glycerol interactions
      occurring to allow a separate glass formation process for glycerol.

PMID- 16787006
TI  - Studies on kinetics and thermostability of a novel acid invertase from Fusarium
      solani.
AB  - The present investigation deals with purification and thermal characterization of
      an acid invertase produced by Fusarium solani in submerged culture. The maximum
      enzyme activity (9.90 U mL(-1)) was achieved after 96 h of cultivation at pH 5.0
      and 30 degrees C in a basal medium containing molasses (2%) as the carbon and
      energy source supplemented with 1% peptone. Invertase was purified by ammonium
      sulfate fractionation and column chromatography on DEAE-cellulose and Sephadex G
      200. The purified enzyme was proven to be homogeneous by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The molecular mass of the enzyme was 65 kDa.
      The optimum pH and temperature for activity were 2.6 and 50 degrees C,
      respectively. The Km value for sucrose was 3.57 mM with an activation energy of
      4.056 kJ mol(-1). Enthalpies of activation (DeltaH) were decreased while
      entropies (DeltaS) of activation increased at higher temperatures. The effects of
      alpha-chymotrypsin and 4 M urea were tetraphasic with periodic gain and loss of
      enzyme activity. A possible explanation for the thermal inactivation of invertase
      at higher temperatures is also discussed.

PMID- 16787007
TI  - Heat-stable phytases in transgenic wheat (Triticum aestivum L.): deposition
      pattern, thermostability, and phytate hydrolysis.
AB  - The present paper addresses the question of thermotolerance of in planta
      synthesized heterologous enzymes using phytase as a model. Two individual
      transgenic wheat materials expressing an Aspergillus fumigatus phytase with a low
      denaturation temperature (62.5 degrees C) but a high refolding capacity, and a
      rationally designed consensus phytase engineered to a high denaturation
      temperature (89.3 degrees C), were evaluated. High levels of endosperm specific
      expression were ensured by the wheat high molecular weight glutenin 1DX5
      promoter. Immunodetection at the light and electron microscopical level shows
      unequivocally that the heterologous phytase is deposited in the vacuole, albeit
      that the transformation constructs were designed for secretion to the apoplast.
      Evaluation of heat stability properties and kinetic properties unraveled that,
      under these deposition conditions, heat stability based on high unfolding
      temperature is superior to high refolding capacity and represents a realistic
      strategy for improving phosphate and mineral bioavailability in cereal-based feed
      and food.

PMID- 16787008
TI  - Piceid (resveratrol glucoside) synthesis in stilbene synthase transgenic apple
      fruit.
AB  - A stilbene synthase gene along with the selectable marker gene bar for herbicide
      resistance was transferred via Agrobacterium tumefaciens mediated transformation
      into apple (Malus domesticaBorkh.) cvs. 'Elstar' and 'Holsteiner Cox'. The
      stilbene synthase catalyzes the conversion of 1 molecule of p-coumaroyl-CoA and 3
      molecules of malonyl-CoA into 3,4',5-trihydroxystilbene, commonly known as
      resveratrol. This phytoalexin has implications in both phytopathology and human
      health. Greenhouse-grown transgenic and nontransformed control plants were
      grafted onto dwarfing rootstock M27. Flowering and fruiting occurred within the
      following years, offering the opportunity to analyze transgenic apple fruit and
      fertility of transgenic plants as well as inheritance of the transgenes into the
      seedling progeny. Molecular analysis revealed that the stilbene synthase is
      expressed in transgenic plants and in the skin and flesh of transgenic apple
      fruit. After formation, resveratrol is modified by the addition of a hexose
      sugar. The resulting component was characterized as piceid. With the aim of
      characterizing the influence of the novel biosynthetic pathway on the
      accumulation of other phenolic compounds naturally present in apple fruit, the
      amounts of flavanols, flavonols, phloretin derivatives and hydroxycinnamic acids
      in wild type and transgenic fruit were determined by HPLC. In all investigated
      transformed lines that accumulated piceid, no negative correlation between levels
      of piceid and the above-mentioned compounds was observed, except for the flavonol
      contents, which slightly decreased. Inheritance of the transgenes was confirmed
      in the seedling progeny, which were obtained after pollination of transgenic
      plants with nontransgenic pollen and vice versa after pollination of
      nontransgenic plants with pollen obtained from transgenic plants. The fertility
      of stilbene synthase transgenic plants was demonstrated. To the authors'
      knowledge this is the first time that data are available on piceid synthesis in
      transgenic apple fruit and the effects of its accumulation on levels of other
      phenolic compounds present in the fruit.

PMID- 16787009
TI  - Immobilization of angiotensin-converting enzyme on glyoxyl-agarose.
AB  - The assay of angiotensin-converting enzyme (ACE) inhibition by food-derived
      peptides is usually carried out by using soluble ACE in a batch process. The
      purification of this enzyme from tissues is not an easy task, and the resulting
      preparation loses activity very fast. In addition, ACE commercial preparations
      are very expensive. In this work the immobilization of ACE, through lysine amino
      groups, to 4% beads cross-linked (4 BCL) glyoxyl-agarose is described. The amount
      of immobilized enzyme increased with increasing concentrations of enzyme and with
      incubation time until a saturation point was reached at 50 mg protein/mL gel and
      3.5 hours, respectively. The IC50 values for a noncompetitive sunflower peptide
      inhibitor were similar for the soluble (30.56 microM) and immobilized (32.7
      microM) enzymes. An immobilized derivative was obtained that was 60 times more
      stable than the soluble enzyme at 60 degrees C. This procedure yields a
      derivative that can be reused and has increased thermal stability compared to
      that of the soluble enzyme. Thus, ACE immobilization is a good alternative to
      using soluble freshly prepared or commercial preparations because of economical
      and practical reasons.

PMID- 16787010
TI  - Biocatalytic synthesis of butein and sulfuretin by Aspergillus alliaceus.
AB  - Aspergillus alliaceus UI315 was examined for its potential to catalyze
      biotransformation reactions of chalcones that mimic plant biosynthetic processes.
      3-(4' '-Hydroxyphenyl)-1-(2',4'-dihydroxyphenyl)propenone (4,2',4'
      trihydroxychalcone, isoliquiritigein) (1) was efficiently transformed to two
      major metabolites that were isolated chromatographically and identified by
      spectroscopic methods as 3-(3' ',4' '-dihydroxyphenyl)-1-(2',4'
      dihydroxyphenyl)propenone (butein) (7) and 2-[(3,4-dihydroxyphenyl)methylene]-6
      hydroxy-3(2H)benzofuranone (7,3',4'-trihydroxyaurone, sulfuretin) (10).
      Inhibition experiments suggested that initial C-3 hydroxylation of 1 to 7 was
      catalyzed by a cytochrome P450 enzyme system. A second A. alliaceus enzyme,
      partially purified and identified as a catechol oxidase, catalyzed the oxidation
      of the catechol butein (7) likely through an ortho-quinone (8) that cyclized to
      the aurone product 10. This work showed that A. alliaceus UI315 contains
      oxidative enzyme systems capable of converting phenolic chalcones such as 1 into
      aurones such as 10 in a process that mimics plant biosynthetic pathways.

PMID- 16787011
TI  - Electrochemical modification of the redox potential of pasteurized milk and its
      evolution during storage.
AB  - Several modifications that occur in milk during its processing and storage are
      driven by different oxidation-reduction reactions. In this study, a smooth
      electrolytic process was used to modify the redox state of the active species of
      milk thereby creating a mean to control these reactions. Five electroreduction
      treatments (2, 4, 6, 8, and 10 V) were applied to pasteurized skim milk.
      Parameters such as redox potential, dissolved oxygen, pH, conductivity, and
      current intensity were monitored during the course of each treatment. The
      proposed technology allows modulation of the redox potential of milk. Significant
      decreases of redox potential (441-707 mV) and of dissolved oxygen (3.3-8.3 mg L(
      1)) were obtained. However, the results suggest that only a short-term modulation
      is created and that natural "milk equilibrium" is reestablished after 4-5 days of
      storage depending on the voltage difference applied during the electrochemical
      treatment.

PMID- 16787012
TI  - Monitoring of changes in substrate characteristics during mushroom compost
      production.
AB  - Substrates from three mushroom compost facilities in Northern Ireland, employing
      similar production technologies, were examined to assess the quality of the
      compost produced. Biochemical investigation highlighted changes in substrates
      through each step of the production cycle. Thermogravimetric analysis (TGA)
      provided useful information on fiber fraction content and extent of substrate
      breakdown. A comparison of productivity, chemical, and thermal data permitted
      assessment of the degree of bioconversion that had occurred in the decomposition
      from raw materials to finished substrate for each composter. One of the
      composters consistently produced substrate of inferior quality compared to the
      other two, indicating production inefficiencies during composting. Results
      demonstrated that allied to chemical analyses, TGA is a useful tool, providing
      valuable information on substrate quality and, in particular, for studying the
      bioconversion of lignocellulosic materials in mushroom compost.

PMID- 16787013
TI  - Oxidation of glycerol in the presence of hydrogen peroxide and iron in model
      solutions and wine. Potential effects on wine color.
AB  - Wine oxidation appears to include the formation of hydroxyl radical (*OH), an
      exceptionally reactive and thus nonselective compound that might be involved in
      the production of important aldehydes and ketones. This experiment examined the
      *OH oxidation of glycerol, a major wine constituent, and thus a likely target of
      such oxidation, in model wine, generated by hydrogen peroxide and iron catalysis.
      The oxidation products generated were analyzed as their hydrazones using LC
      DAD/MS. Glyceraldehyde and dihydroxyacetone were the main compounds identified,
      both of which were also observed in naturally aged and *OH-oxidized wines. As
      anticipated, the presence of ethanol in the model wine did not preclude the
      formation of these compounds. Additionally, when a young red wine was treated
      with these oxidation derivatives, a noteworthy increase in color was observed,
      most likely due to the formation of novel anthocyanin-based structures.

PMID- 16787014
TI  - Combined effect of modified atmosphere packaging and addition of rosemary
      (Rosmarinus officinalis), ascorbic acid, red beet root (Beta vulgaris), and
      sodium lactate and their mixtures on the stability of fresh pork sausages.
AB  - The effects of rosemary, in combination with ascorbic acid, red beet root, and
      sodium lactate, as well as their mixtures, on the inhibition of both lipid and
      pigment oxidation of fresh pork sausages packaged in a modified atmosphere were
      studied. Sausages (240) were packaged in a 80% O2 + 20% CO2 gas mixture and
      analyzed for CIE a, metmyoglobin, TBARS, psychrotrophic aerobes, and sensory
      discoloration and off-odor throughout 20 days of storage at 2 +/- 1 degrees C.
      The mixture of rosemary + ascorbic acid + sodium lactate + red beet root extract
      extended the shelf life of fresh pork sausages from 8 to 16 days. Results
      demonstrated that all of the components of the mixture contributed to obtaining
      the maximum delay in color and/or odor decay, due to a combined inhibitory action
      on both pigment and lipid oxidation, as well as on microbial growth.

PMID- 16787015
TI  - Sucrose, glucose, and fructose extraction in aqueous carrot root extracts
      prepared at different temperatures by means of direct NMR measurements.
AB  - Solutions obtained by heating carrot roots in water (stocks) are widely used in
      the food industry, but little information is available regarding the metabolites
      (intermediates and products of metabolism) found in the stock. The effect of
      treatment temperature and duration on the sugar composition of stocks was
      investigated directly by quantitative (1)H NMR spectroscopy, to understand the
      extraction mechanism when processing at 100 degrees C. Stocks prepared at three
      different temperatures (50, 75, and 100 degrees C) were investigated for up to 36
      h. Three sugars (sucrose, glucose, and fructose) were detected and quantified.
      The concentrations of these three sugars reached a maximum after 9 h when the
      temperature of treatment was 50 or 75 degrees C. At 100 degrees C, the sucrose
      concentration reached a maximum after 3 h, whereas the concentration of glucose
      and fructose was still increasing at that time. Comparison of the kinetic
      composition of these carrot stocks with that of model sugar solutions leads to
      the proposal that the changes in stock composition result from sugar diffusion,
      sucrose hydrolysis, and hydroxymethylfurfural (HMF) formation.

PMID- 16787016
TI  - Controlled proteolysis and the properties of milk gels.
AB  - Milk gels induced by partial proteolysis of the kappa-casein followed by
      acidification were studied, and their gelation behavior was compared to that of
      milk gels induced by simultaneous acidification and renneting, using dynamic
      rheology. There were generally two stages (at pH values below and above 5.0) in
      the gelation of the milk whose kappa-casein had been partially proteolyzed and
      acidified. The onset of gelation was at higher pH as the degree of kappa-casein
      proteolysis increased. The development of G' immediately after the onset of
      gelation was faster in the milk gels induced by simultaneous acidification and
      renneting, because of the continuing kappa-casein proteolysis. Preheat treatment
      caused the onset of gelation to occur at higher pH than for unheated milk.
      However, the maximum tan delta during gelation always occurred at the same pH
      (for a given concentration of acidulant), and its value and position were
      independent of the extent of renneting and whether the milks had been heat
      treated. The results are discussed in terms of the interactions between casein
      micelles occurring during gelation.

PMID- 16787017
TI  - Anthocyanin composition in black, blue, pink, purple, and red cereal grains.
AB  - Anthocyanin pigments from a wide variety of edible and ornamental black, blue,
      pink, purple, red, and white wheat, barley, corn, rice, and wild rice were
      identified and quantified to evaluate their potential as natural colorants or
      functional food ingredients. The total anthocyanin contents varied significantly
      and exhibited a range of 7-3276 microg/g. Some grains, such as red rice and black
      rice, contained a limited number of pigments, whereas others, such as blue, pink,
      purple, and red corns, had complex anthocyanin profiles. Of the 42 anthocyanin
      compounds observed, 9 were characterized by comparison of the spectroscopic and
      chromatographic properties with those of authentic standards. The remaining
      compounds were tentatively identified on the basis of spectroscopic properties
      and electrospray ionization mass spectra. The most abundant anthocyanins were
      cyanidin 3-glucoside in black and red rices and in blue, purple, and red corns,
      pelargonidin 3-glucoside in pink corn, and delphinidin 3-glucoside in blue wheat.

PMID- 16787018
TI  - Chemical composition of selected edible nut seeds.
AB  - Commercially important edible nut seeds were analyzed for chemical composition
      and moisture sorption. Moisture (1.47-9.51%), protein (7.50-21.56%), lipid (42.88
      66.71%), ash (1.16-3.28%), total soluble sugars (0.55-3.96%), tannins (0.01
      0.88%), and phytate (0.15-0.35%) contents varied considerably. Regardless of the
      seed type, lipids were mainly composed of mono- and polyunsaturated fatty acids
      (>75% of the total lipids). Fatty acid composition analysis indicated that oleic
      acid (C18:1) was the main constituent of monounsaturated lipids in all seed
      samples. With the exception of macadamia, linoleic acid (C18:2) was the major
      polyunsaturated fatty acid. In the case of walnuts, in addition to linoleic acid
      (59.79%) linolenic acid (C18:3) also significantly contributed toward the total
      polyunsaturated lipids. Amino acid composition analyses indicated lysine (Brazil
      nut, cashew nut, hazelnut, pine nut, and walnut), sulfur amino acids methionine
      and cysteine (almond), tryptophan (macadamia, pecan), and threonine (peanut) to
      be the first limiting amino acid as compared to human (2-5 year old) amino acid
      requirements. The amino acid composition of the seeds was characterized by the
      dominance of hydrophobic (range = 37.16-44.54%) and acidic (27.95-33.17%) amino
      acids followed by basic (16.16-21.17%) and hydrophilic (8.48-11.74%) amino acids.
      Trypsin inhibitory activity, hemagglutinating activity, and proteolytic activity
      were not detected in the nut seed samples analyzed. Sorption isotherms (Aw range
      = 0.08-0.97) indicated a narrow range for monolayer water content (11-29 mg/g of
      dry matter). No visible mold growth was evident on any of the samples stored at
      Aw < 0.53 and 25 degrees C for 6 months.

PMID- 16787019
TI  - Time course of the evolution of malic and lactic acids in the alcoholic and
      malolactic fermentation of grape must by quantitative 1H NMR (qHNMR)
      spectroscopy.
AB  - Quantitative NMR can be used to monitor several processes that take place in the
      transformation of the must of wine grapes. The study described here focused
      attention on monitoring of the malic and lactic acid levels during the alcoholic
      and malolactic fermentation processes. The method allows the simultaneous
      quantification of both acids through a range of 1-3.2 mmol/L. The effectiveness
      of each process was assessed and compared by carrying out precise analyses using
      enzymatic methods.

PMID- 16787020
TI  - Residue levels and effectiveness of pyrimethanil vs imazalil when using heated
      postharvest dip treatments for control of Penicillium decay on citrus fruit.
AB  - The influence of fungicide concentration and treatment temperature on residue
      levels of pyrimethanil (PYR) in comparison with the commonly used fungicide
      imazalil (IMZ) was investigated in orange fruits following postharvest dip
      treatments. The dissipation rate of PYR residues was recorded as a function of
      storage conditions. The fungicide efficacy against green and blue molds caused by
      Penicillium digitatum and Penicillium italicum, respectively, was evaluated on
      different citrus varieties following the fungicide application at 20 or 50
      degrees C. Residue levels of PYR in Salustiana oranges were significantly
      correlated with the fungicide dosage, but residue concentrations were notably
      higher (ca. 13-19-fold) after treatment at 50 degrees C as compared to treatments
      at 20 degrees C. After treatment at temperatures ranging from 20 to 60 degrees C,
      PYR and IMZ residues in Salustiana oranges were significantly correlated with dip
      temperatures. Dissipation rates of PYR during storage were negligible in both
      Salustiana and Tarocco oranges. Results obtained on wounded, noninoculated Miho
      satsumas revealed that when treatments were performed at 50 degrees C, PYR or IMZ
      concentrations needed to achieve the complete control of decay were 8- and 16
      fold less than by treatment at 20 degrees C. When fruits were inoculated with
      either P. digitatum or P. italicum, the application of 400 mg L(-1) PYR at 20
      degrees C or 100 mg L(-1) PYR at 50 degrees C similarly reduced green and blue
      mold development. These results were corroborated by storage trials on Marsh
      grapefruits and Tarocco oranges. The lowest concentration of PYR required to
      achieve almost total protection of the fruit against decay accounted for 100 mg
      L(-1) at 50 degrees C and 400 mg L(-1) at 20 degrees C, respectively. Treatments
      did not affect fruit external appearance, flavor, and taste. It is concluded that
      postharvest PYR treatment represents an effective option to control green and
      blue mold in citrus fruit and that integration of fungicide applications and hot
      water dips may reduce the possibility of selecting fungicide-resistant
      populations of the pathogen, as a consequence of increased effectiveness of the
      treatment.

PMID- 16787021
TI  - Development of controlled release formulations of carbofuran and evaluation of
      their efficacy against Meloidogyne incognita.
AB  - Controlled release (CR) formulations of the insecti-nematicide carbofuran have
      been prepared using commercially available rosin, sodium carboxymethylcellulose
      and sodium carboxymethylcellulose with clay (bentonite, kaolinite, and Fuller's
      earth). The kinetics of carbofuran release in soil from the different
      formulations were studied in comparison with that of the commercially available
      granules (3G). Release from the commercial formulation was faster than with the
      new CR formulations. Addition of clay in the biodegradable polymer matrix reduced
      the rate of release. The diffusion exponent (n value) of carbofuran in soil
      ranged from 0.462 to 0.740 in the tested formulations. The half-release (t1/2)
      values ranged between 4.79 and 25.11 days, and the period of optimum availability
      (POA) of carbofuran ranged from 15.10 to 43.97 days. The mean EC50 of the
      commercial formulation against Meloidogyne incognita was quite high as compared
      to those of CR formulations. The effective duration (te) of carbofuran from the
      CR and commercial formulations was predicted by fitting the mean EC50 values of
      test formulations in the model (M(infinity) - Me)/M(infinity) = Kdte. It was 0.7
      day in commercial 3G in comparison with 17.8 days for CMC-bentonite. The bioassay
      studies revealed that with the rosin-yellow polymer, the dose of carbofuran could
      be reduced to half of its recommended dose for nematode control. Overall, a
      comparison of CR formulations with the commercial one showed an earlier
      degradation of carbofuran in the latter and relatively prolonged activity in the
      former.

PMID- 16787022
TI  - Biodegradation of the fungicide iprodione by Zygosaccharomyces rouxii strain
      DBVPG 6399.
AB  - Iprodione is a contact fungicide used to control several pathogens such as
      Botrytis cinerea, Monilia, and Sclerotinia. This paper reports the ability of an
      iprodione-resistant strain of Zygosaccharomyces rouxii to degrade iprodione at a
      concentration of 1 mg L(-1). The yeast Z. rouxii was chosen also for its ability
      to grow at high osmolarity. Also of note is that in bioremediation situations and
      in the food industry such resistance could be important. The kinetic and
      metabolic behaviors of the fungicide in the media are described. The results show
      a new transformation pathway of iprodione by the yeast leading to the formation
      of N-(3,5-dichlorophenyl)-2,4-dioxoimidazoline, 3-isopropylhydantoin, and 3,5
      dichloroaniline. These compounds were identified by 1H NMR, 13C NMR, and GC-MS
      analyses. This study provides a basis to employ yeast strains in biodegradation
      studies in relation to their ability in the disappearance and degradation of
      xenobiotics into simpler molecules.

PMID- 16787023
TI  - Acid- and base-catalyzed hydrolysis of chloroacetamide herbicides.
AB  - Despite the prevalence of chloroacetamides as herbicides, little is known about
      the rates or products of acid- or base-catalyzed hydrolysis of these compounds.
      Mechanisms of acid-catalyzed reactions may parallel those catalyzed by
      (hydr)oxide minerals, while base-catalyzed processes have as important
      counterparts reactions with environmental nucleophiles (such as reduced sulfur
      species). The current study systematically investigates how the structure of nine
      chloroacetamides affects their reactivity in 2 N NaOH, 2 N HCl, or 6 N HCl at 25
      or 85 degrees C. Base-catalyzed hydrolysis proceeds either through an
      intermolecular SN2 reaction to hydroxy-substituted derivatives or (in a few
      cases) through amide cleavage, while both amide and ether group cleavages are
      observed under acidic conditions. Our results reveal that subtle differences in
      chloroacetamide structure [notably the type of (alkoxy)alkyl substituent] can
      dramatically influence reactivity and reaction mechanism. Hydroxy-substituted,
      morpholinone, and secondary aniline derivatives were identified upon reaction for
      several years in deionized water at circumneutral pH.

PMID- 16787024
TI  - Influence of methanol on the dynamics of the retention and release of cyprodinil
      by an agricultural soil.
AB  - The influence of methanol on the adsorption of the fungicide cyprodinil by a crop
      soil was studied by equilibrium measurements and by determining the retention
      release dynamics in a continuous stirred flow tank reactor (CSTR). Equilibrium
      measurements showed the effective coefficient of partition of cyprodinil between
      soil and solution, K(dc), decreases linearly as the concentration of methanol in
      the solution increases until a percentage of 20% is reached. In CSTR experiments,
      the retention of cyprodinil was found to be almost reversible; up to a 95% of the
      fungicide was desorbed. The retention-release dynamics showed biphasic behavior
      and was partially controlled by diffusion. This behavior was reproduced by a
      model of diffusion into micropores identifying the soil particles as spheres and
      taking into account both intraparticle nonlinear adsorption and nonlinear
      adsorption at external surfaces. In all cases, the sorption kinetics was not the
      limiting step. The main effect of methanol in the retention-release dynamics
      ended up being based on the changes produced in the adsorption equilibrium.
      Methanol also increased the effective diffusion coefficient and decreased the
      mass transfer coefficient. The optimized Freundlich's isotherm coefficients for
      <5% methanol were lower than those obtained from the batch experiments.

PMID- 16787025
TI  - Circulating fluidized bed combustion product addition to acid soil: alfalfa
      (Medicago sativa L.) composition and environmental quality.
AB  - To reduce S emissions, petroleum coke with a high concentration of S was
      combusted with limestone in a circulating fluidized bed (CFB) boiler. The
      combustion process creates a bed product that has potential for agricultural
      uses. This CFB product is often alkaline and enriched in S and other essential
      plant nutrients, but also contains high concentrations of Ni and V. Agricultural
      land application of CFB product is encouraged, but little information is
      available related to plant responses and environmental impacts. CFB product and
      agricultural lime (ag-lime) were applied at rates of 0, 0.5, 1.0, and 2.0 times
      the soil's lime requirement (LR) to an acidic soil (Wooster silt loam). The 2.0x
      LR application rate of CFB product was equivalent to 67.2 Mg ha(-1). Alfalfa
      yield was increased 4.6 times by CFB product and 3.8 times by ag-lime compared to
      untreated control. Application of CFB product increased the concentration of V in
      soil and alfalfa tissue, but not in soil water, and increased the concentration
      of Ni in soil and soil water, but not in alfalfa tissue. However, these
      concentrations did not reach levels that might cause environmental problems.

PMID- 16787026
TI  - Effect of the simultaneous addition of beta-cyclodextrin and the herbicide
      norflurazon on its adsorption and movement in soils.
AB  - The effects of beta-cyclodextrin (BCD) on the sorption-desorption and transport
      processes of the herbicide norflurazon (NFL) in soils of different
      characteristics when both are applied simultaneously have been investigated.
      Adsorption-desorption studies of NFL on six soils of very different
      characteristics in the presence of BCD have been performed using a batch
      equilibration method and correlated to its mobility in homogeneous hand-packed
      soil columns. NFL determinations were undertaken by HPLC equipped with a diode
      array detector at a wavelength of 220 nm. BCD was also analyzed by HPLC with
      fluorimetric detection using a postcolumn reaction. The interaction of NFL with
      BCD yielded the formation of an inclusion complex in solution. When this complex
      is applied to soils, a large decrease in NFL adsorption capacity and an increase
      in its desorption were observed, due to the higher tendency of NFL-BCD complexes
      to remain in solution. The results obtained in adsorption and soil column
      experiments indicated that the influence of BCD on NFL mobility and availability
      depends on the different affinities of BCD to be sorbed on soils of different
      characteristics and on the concentration of BCD used. The lower the concentration
      of BCD added, the more tenaciously it adheres to the soil, and most of the BCD
      molecules would be adsorbed, providing a coating to soil particles that acts as a
      bridge between NFL and the soil surface, acting as an adsorbent and retarding the
      mobility of the herbicide. At higher concentrations of BCD, or in soils where its
      adsorption is very low, most of the BCD molecules are in the aqueous phase and
      NFL molecules tend to be complexed with BCD in solution, acting then as a
      solubilizing agent.

PMID- 16787027
TI  - Surfactant-modified zeolite as a slow release fertilizer for phosphorus.
AB  - The feasibility of using surfactant-modified zeolite (SMZ) as a carrier for
      fertilizer and for slow release of phosphorus (P) was investigated. Zeolite-A was
      modified by using hexadecyltrimethylammonium bromide, a cationic surfactant, to
      modify its surface to increase its capacity to retain anion, namely, phosphate
      (PO4(3-)). SMZ was thoroughly characterized using X-ray diffraction, Fourier
      transform infrared, and scanning electron microscopy to study the effect of
      surfactant modification. Zeolite-A and SMZ were then subjected to P loading by
      treating them with fertilizer (KH2PO4). It was observed that the P loading on SMZ
      increased by a factor of 4.9 as compared to the unmodified zeolite-A. A
      comparative study of the release of P from fertilizer-loaded unmodified zeolite-A
      and SMZ and from solid KH2PO4 was performed using the constant flow percolation
      reactor. The results show that the P supply from fertilizer-loaded SMZ was
      available even after 1080 h of continuous percolation, whereas P from KH2PO4 was
      exhausted within 264 h. The results indicate that SMZ is a good sorbent for PO4(3
      ), and a slow release of P was achievable. These properties suggest that SMZ has
      a great potential as the fertilizer carrier for slow release of P.

PMID- 16787028
TI  - Chemical composition of the essential oils of serbian wild-growing Artemisia
      absinthium and Artemisia vulgaris.
AB  - The chemical composition of the aerial and root essential oils, hydrodistilled
      from Artemisia absinthium L. and Artemisia vulgaris L. (wild-growing populations
      from Serbia), were studied by gas chromatography, gas chromatography-mass
      spectrometry, and 13C nuclear magnetic resonance. During the storage of plant
      material under controlled conditions, a significant decrease of essential oil
      yields (isolated directly after drying and after 1 year of storage) and
      significant differences in their chemical compositions were observed. A possible
      mechanism for the observed oil component interconversion has been discussed. The
      noticeable differences in the chemical composition of the oils isolated from
      roots and aerial parts of A. absinthium and A. vulgaris were also correlated with
      the diverging biosynthetic pathways of volatiles in the respective plant organs.
      The antimicrobial activities against the common human pathogens of all of the
      isolated oils were tested according to National Committee on Clinical Laboratory
      Standards. The oils showed a broad spectrum of antimicrobial activity against the
      tested strains. Therefore, these oils can be used as flavor and fragrance
      ingredients.

PMID- 16787029
TI  - Changes induced by UV radiation during virgin olive oil storage.
AB  - The effects of UV radiation on the chemical and sensory characteristics of virgin
      olive oils (cv. Arbequina and Picual) were assessed. Even small doses of UV
      radiation induced oxidation of the virgin olive oil samples. Total phenols and
      fatty acids contents decreased during the process as well as the intensity of the
      bitter and fruity sensory attributes, while the intensity of the rancid sensory
      attribute notably increased. Acetaldehyde, 2-butenal, 2-pentenal, octane,
      octanal, hexanal, nonanal, and 2-decenal were the volatile compounds most
      affected, showing an important increase during the irradiation process. Nonanal,
      hexanal, and pentanal showed high correlation with the rancid sensory attribute
      (90%, 86%, and 86%, respectively). 2-Decenal and nonanal concentrations allowed
      us to predict the alteration level of the samples by mean of multiple Ridge
      regression.

PMID- 16787031
TI  - Model studies on the efficacy of protein homogenates from raw pork muscle and dry
      cured ham in binding selected flavor compounds.
AB  - The binding of sarcoplasmic and myofibrillar proteins extracted from postrigor
      pork muscle and from 7 and 12 months dry-cured hams with volatile compounds such
      as 3-methyl-butanal, 2-methyl-butanal, 2-pentanone, hexanal, methional, and
      octanal was studied using solid phase microextraction and gas chromatography
      analysis. The binding ability of sarcoplasmic proteins from pork muscle was
      higher than the ability shown by 7 and 12 months dry-cured ham sarcoplasmic
      homogenates and also higher than the binding ability of myofibrillar homogenates.
      The effect of the ionic strength on the binding was also studied. This effect was
      more important on myofibrillar proteins due to its ability to produce changes on
      the protein conformation that affect their binding ability. However, the
      sarcoplasmic protein binding ability was more related to the small compounds
      present in this homogenate than with the aqueous phase ionic strength.

PMID- 16787030
TI  - Characterization of epoxydecenal isomers as potent odorants in black tea
      (Dimbula) infusion.
AB  - In a black tea (Dimbula) infusion, the potent "sweet and/or juicy" odorants were
      identified as the cis- and trans-4,5-epoxy-(E)-2-decenals by comparison of their
      gas chromatography retention indices, mass spectra, and odor quality to those of
      the actual synthetic compounds. Of the two odorants, cis-4,5-epoxy-(E)-2-decenal
      has been identified for the first time in the black tea. On the basis of the
      aroma extract dilution analysis on the flavor distillate obtained using the
      solvent-assisted flavor evaporation technique from the black tea infusion, these
      isomers showed higher flavor dilution (FD) factors. The FD factors and
      concentrations of these odorants in the black tea infusion were observed to be
      much higher than those from Japanese green tea. In addition, the model studies
      showed that these odorants were generated from linoleic acid and its
      hydroperoxides by heating, but the generated amounts of these odorants from
      linoleic acid were much less than those of its hydroperoxides. It can be assumed
      from these results that the withering and fermentation, which are characteristic
      processes during the manufacturing of the black tea, which includes the enzymatic
      reaction such as lipoxygenase, is one of the most important factors for the
      formation of the epoxydecenal isomers.

PMID- 16787032
TI  - Volatile composition and contribution to the aroma of spanish honeydew honeys.
      Identification of a new chemical marker.
AB  - Honeydew honeys from holm-oak, oak, and forest were isolated for aroma compounds
      by simultaneous distillation-extraction and analyzed by gas chromatography-mass
      spectrometry. In all, 66 volatile components were identified and quantified.
      trans-Oak lactone, a characteristic volatile component of oak wood, is proposed
      as a new chemical marker for the plant origin of honeydew honeys. Other
      compounds, such as aminoacetophenone and propylanisol, could be considered
      characteristic of holm-oak honeydew honeys. A total of 15 volatile compounds
      presented odor activity values (OAVs) greater than 1, with phenylacetaldehyde and
      beta-damascenone being those with the highest OAVs.

PMID- 16787033
TI  - Identification of monomenthyl succinate in natural mint extracts by LC-ESI-MS-MS
      and GC-MS.
AB  - Fresh and dried mint leaves Mentha piperita (peppermint) and Mentha spicata
      (spearmint) were extracted in two different ways and the extracts investigated by
      high performance liquid chromatography-tandem mass spectrometry. All the
      ethanolic extracts prepared with Soxhlet apparatus were used in the
      identification of monomenthyl succinate as previously reported. The highest level
      was found in fresh spearmint leaves. The analysis of the extractions, prepared
      under mild conditions using a fluorinated solvent (HFC 134-a), confirmed the
      natural occurrence of monomenthyl succinate in the leaves, ruling out the
      hypothesis that this constituent could be an artifact of the Soxhlet extraction
      process. A method for identifying this compound in such a fluorinated solvent
      extract of mint leaf using preliminary esterification with diazomethane and then
      GC-MS is described.

PMID- 16787034
TI  - Difference in the volatile composition of pine-mushrooms (Tricholoma matsutake
      Sing.) according to their grades.
AB  - The differences in volatile components of pine-mushrooms (Tricholoma matsutake
      Sing.) according to their grades were observed by applying multivariate
      statistical methods to GC-MS data sets. A total of 35 and 37 volatile components
      were identified in raw and cooked pine-mushrooms, respectively. The volatile
      components in pine-mushrooms were primarily composed of C8 species, such as 3
      octanol, 1-octen-3-ol, 1-octanol, (E)-2-octen-1-ol, 3-octanone, 1-octen-3-one,
      (E)-2-octenal, and octanoic acid. The levels of ethyl octanoate, junipene, and 3
      methyl-3-buten-2-one were much higher in raw pine-mushroom of higher grades,
      whereas the reverse was true for C8 components. On the other hand, furfuryl
      alcohol, benzyl alcohol, phenylethyl alcohol, dihydro-5-methyl-2(3H)-furanone,
      2(5H)-furanone, (E)-2-methyl-2-butenal, furfural, phenylacetaldehyde, benzoic
      acid methyl ester, camphene, and beta-pinene were the major components of cooked
      mushrooms. These volatile components formed by various thermal reactions could be
      mainly responsible for the difference in volatile components of cooked pine
      mushrooms according to their grades.

PMID- 16787035
TI  - Antioxidant and antiradical activities in extracts of hazelnut kernel (Corylus
      avellana L.) and hazelnut green leafy cover.
AB  - Phenolic compounds in the aqueous systems were extracted, from hazelnut kernel
      (HK) and hazelnut green leafy cover (HGLC), with 80% (v/v) ethanol (HKe and
      HGLCe) or 80% (v/v) acetone (HKa and HGLCa). The extracts were examined for their
      phenolic and condensed tannin contents and phenolic acid profiles (free and
      esterified fractions) as well as antioxidant and antiradical activities by total
      antioxidant activity (TAA), antioxidant activity in a beta-carotene-linoleate
      model system, scavenging of DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, and
      reducing power. Significant differences (p < 0.05) in the contents of total
      phenolics, condensed tannins, and TAA existed among the extracts that were
      examined. HGLCa extract had the highest content of total phenolics (201 mg of
      catechin equivalents/g of extract), condensed tannins (542 mg of catechin
      equivalents/g of extract), and TAA (1.29 mmol of Trolox equivalents/g of extract)
      followed by HGLCe, HKa, and HKe extracts, respectively. Five phenolic acids
      (gallic acid, caffeic acid, p-coumaric acid, ferulic acid, and sinapic acid) were
      tentatively identified and quantified, among which gallic acid was the most
      abundant in both free and esterified forms. The order of antioxidant activity in
      a beta-carotene-linoleate model system, the scavenging effect on DPPH radical,
      and the reducing power in all extracts were in the following order: HGLCa > HGLCe
      > HKa > HKe. These results suggest that both 80% ethanol and acetone are capable
      of extracting phenolics, but 80% acetone was a more effective solvent for the
      extraction process. HGLC exhibited stronger antioxidant and antiradical
      activities than HK itself in both extracts and could potentially be considered as
      an inexpensive source of natural antioxidants.

PMID- 16787036
TI  - Comparison of the physicochemical properties and ultrastructure of japonica and
      indica rice grains.
AB  - The physicochemical properties and ultrastructures of japonica vs indica rice
      varieties and waxy vs nonwaxy rice varieties were compared. The viscogram values
      of the indica varieties were significantly higher than those of the japonica
      varieties. The gelatinization temperatures, breakdown, and setback were
      significantly lower for waxy than for nonwaxy rice varieties. Japonica rice
      exhibited lower hardness but higher adhesiveness than indica rice. The air space
      between individual starch granules was larger for waxy than for nonwaxy rice. The
      starch granules were compact in japonica rice, while the compound starch granules
      of indica rice were much smaller than those of japonica rice and were scattered
      widely in the endosperm. The protein bodies in japonica rice were concentrated
      near the cell wall, whereas those in indica rice were scattered around
      amyloplasts. These results suggest that the ultrastructure of rice affects the
      texture of the cooked product.

PMID- 16787037
TI  - Simulated digestion of Vitis vinifera seed powder: polyphenolic content and
      antioxidant properties.
AB  - There is increasing evidence that reactive oxygen species arising from several
      enzymatic reactions are mediators of inflammatory events. Plant preparations have
      the potential for scavenging such reactive oxygen species. Flavans and
      procyanidins are bioavailable and stable during the process of cooking. This
      study used conditions that mimicked digestion of Vitis vinifera seed powder in
      the stomach (acidic preparation) and small intestine (neutral preparation). The
      flavonoids of these two preparations were released during simulated digestion and
      were determined with HPLC analysis. Biochemical model reactions relevant for the
      formation of reactive oxygen species in vivo at inflammatory sites were used to
      determine the antioxidant properties of the two preparations. The inhibition of
      the indicator reaction for the formation of reactive oxygen species represents a
      potential mechanism of the physiological activity of the corresponding
      preparation. The results of this work show clearly that the polyphenols released
      during the simulated digestion of the two preparations have good scavenging
      potential against superoxide radicals, hydroxyl radicals, and singlet oxygen.
      They protect low-density lipoprotein against copper-induced oxidation due to the
      copper-chelating properties and their chain-breaking abilities in lipid
      peroxidation.

PMID- 16787038
TI  - Changes in organosulfur compounds in garlic cloves during storage.
AB  - We determined the changes in the contents of three gamma-glutamyl peptides and
      four sulfoxides in garlic cloves during storage at -3, 4, and 23 degrees C for
      150 days using a validated high-performance liquid chromatography method that we
      reported recently. When garlic was stored at 4 degrees C for 150 days, marked
      conversion of the gamma-glutamyl peptides, gamma-L-glutamyl-S-allyl-L-cysteine
      and gamma-L-glutamyl-S-(trans-1-propenyl)-L-cysteine (GSPC), to sulfoxides,
      alliin and isoalliin, was observed. Interestingly, however, when garlic was
      stored at 23 degrees C, a decrease in GSPC and a marked increase in cycloalliin,
      rather than isoalliin, occurred. To elucidate in detail the mechanism involved,
      the conversion of isoalliin to cycloalliin in both buffer solutions (pH 4.6, 5.5,
      and 6.5) and garlic cloves at 25 and 35 degrees C was examined. Decreases in the
      concentration of isoalliin in both the solutions and the garlic cloves during
      storage followed first-order kinetics and coincided with the conversion of
      cycloalliin. Our data indicated that isoalliin produced enzymatically from GSPC
      is chemically converted to cycloalliin and that the cycloalliin content of garlic
      cloves increases during storage at higher temperature. These data may be useful
      for controlling the quality and biological activities of garlic and its
      preparations.

PMID- 16787039
TI  - Characterization of flavonol conjugates in immature leaves of pak choi [Brassica
      rapa L. Ssp. chinensis L. (Hanelt.)] by HPLC-DAD and LC-MS/MS.
AB  - The flavonoid composition of immature leaves of pak choi [Brassica rapa L. ssp.
      chinensis L. (Hanelt.)] was investigated. Flavonol aglycone content was measured
      in 11 pak choi varieties, indicating significant differences (P < 0.05) in
      content between varieties and relatively high contents of kaempferol and
      isorhamnetin. Levels of quercetin ranged from 3.2 to 6.1 mg/100 g of dry weight
      (DW), whereas levels of isorhamnetin and kaempferol were significantly higher
      (8.1-35.1 and 36.0-102.6 mg/100 g of DW, respectively). A large number of
      glycoside and hydroxycinnamic acid derivatives of quercetin, kaempferol, and
      isorhamnetin were identified in cv. 'Shanghai' by LC/UV-DAD/ESI-MS/MS. The UV-DAD
      data allowed identification of hydroxycinnamic acid derivatives, but detailed
      MS/MS fragmentations were required for the structure elucidation. Pak choi could
      be a potentially important source of dietary flavonols, in particular, kaempferol
      and isorhamnetin.

PMID- 16787040
TI  - Adulteration of apple with pear juice: emphasis on major carbohydrates, proline,
      and arbutin.
AB  - Detection of juice-to-juice adulteration based on chemical composition studies is
      a common method used by government regulatory agencies and food companies. This
      study investigated the use of major carbohydrate (fructose, glucose and sucrose),
      polyol (sorbitol), proline, and phenolic profiles as indicators of pear
      adulteration of apple juice (PAAJ). For this work, a total of 105 authentic apple
      juice samples from 13 countries and 27 authentic pear juice samples from 5
      countries were analyzed. Because the major carbohydrate ranges for these juices
      showed significant overlap their use as markers for PAAJ detection would be very
      limited. It was found that sorbitol and proline means for apple and pear were
      significantly different; however, their broad natural ranges would afford PAAJ at
      levels up to 30% without detection. In addition, careful selection of the pear
      juice used as the adulterant would further limit the usefulness of these markers
      for PAAJ detection. Arbutin was conclusively identified as a marker for pear
      juice on the basis of its presence in all 27 authentic pear samples and its
      absence (<0.5 microg/mL) in all 105 apple juice samples analyzed in this study.
      The application of the developed HPLC-PDA method for arbutin analysis to detect
      PAAJ at levels as low as 2% (v/v) was demonstrated. A confirmation method for the
      presence of arbutin in pure pear juice and apple adulterated with pear juice was
      introduced on the basis of the hydrolysis of arbutin to hydroquinone employing
      beta-glucosidase, with reactant and product monitoring by HPLC-PDA.

PMID- 16787041
TI  - Protein distribution in commercial wet- and dry-milled corn germ.
AB  - To identify high-valued coproducts from commercially processed corn germ, it was
      necessary to determine the effect of processing conditions on corn germ proteins.
      We found that significantly less protein was extracted from commercial wet-milled
      as compared to dry-milled corn germ using Tris, sodium dodecyl sulfate (SDS)
      buffer containing 14 mM 2-mercaptoethanol at 100 degrees C for 10 min. SDS
      polyacrylamide gel electrophoresis (PAGE) revealed a number of proteins with
      molecular masses ranging from approximately 10 to 66 kDa for the dry-milled corn
      germ as compared to only a few significant protein bands centered around 23 kDa
      in the wet-milled corn germ. The protein content of the wet- and dry-milled corn
      germ was approximately the same; however, nonprotein nitrogen values were
      significantly greater for the wet-milled than for the dry-milled germ. The
      distribution of fractionated germ protein freshly excised from the embryo of
      yellow dent corn kernels was more similar to that of dry-milled than wet-milled
      corn. SDS-PAGE of laboratory preparations of wet-milled corn germ more closely
      resembled commercial dry- than wet-milled corn germ, which could be attributed to
      limited microbial growth during steeping in the laboratory preparations.

PMID- 16787042
TI  - Formation of cholesterol oxidation products in marinated foods during heating.
AB  - The objectives of this study were to develop a gas chromatography-mass
      spectrometry (GC-MS) method to analyze the contents of cholesterol oxidation
      products (COPs) in marinated eggs, pork, and juice and to compare the effect of
      heating time and soy sauce or sugar on the formation of COPs. By using a silica
      cartridge for purification and GC-MS with selected ion monitoring for detection,
      seven COPs, including 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol,
      5,6alpha-epoxycholesterol, 5,6beta-epoxycholesterol, 5alpha-cholestane-3beta,
      5,6beta-triol, 5-cholesten-3beta-25-diol, and 7-ketocholesterol, as well as
      internal standard 5alpha-cholestane, were resolved within 16 min by using a HP
      5MS capillary column. During marinating, the levels of most COPs followed an
      increasing trend with increasing heating time. However, a higher amount of COPs
      was generated for ground pork as compared to eggs. The incorporation of soy sauce
      or sugar (1 and 10%) was effective in inhibiting COPs formation, with the latter
      being more pronounced than the former in both marinated eggs and pork.

PMID- 16787043
TI  - Protective effects of extra virgin olive oil phenolics on oxidative stability in
      the presence or absence of copper ions.
AB  - The antioxidant activity of the phenolic fraction of extra virgin olive oil was
      assessed in samples that had a decreasing content of antioxidants in the presence
      and absence of copper ions as a catalyst of autoxidation. The oxidation process
      was evaluated by measuring primary and secondary oxidation products. Changes in
      phenols and tocopherols were investigated by high-performance liquid
      chromatography. Both the total phenol content and their antioxidant activity were
      monitored by spectrophotometric assays (with Folin-Ciocalteu and ABTS*+
      reagents). The important role of phenolic compounds (particularly the o
      diphenols) in protection from autoxidation was confirmed. However, the
      tocopherols were more quickly consumed in oils that had the lowest content of o
      diphenols, which also showed evidence of an ability to chelate copper. In
      particular, a dramatic decrease was observed in the isomeric form of
      decarboxymethyl-oleuropein aglycone after addition of the metal, despite its
      significant increase in samples stored in the absence of copper.

PMID- 16787044
TI  - Regulation of color break in citrus fruits. Changes in pigment profiling and gene
      expression induced by gibberellins and nitrate, two ripening retardants.
AB  - Citrus clementina fruits were repeatedly treated on-tree from mature green until
      breaker stages with either nitrate or gibberellin, two retardants of external
      ripening. The natural color break was characterized by a reduction in chlorophyll
      concentration, a decrease in beta,epsilon-carotenoids, beta-carotene, neoxanthin,
      and all-E-violaxanthin, and an increase in beta,beta-xanthophylls [mainly (9Z)
      violaxanthin and beta-cryptoxanthin]. The two retardants delayed both chlorophyll
      depletion and total carotenoid accumulation and in addition altered carotenoid
      composition. Treated fruits maintained longer the typical carotenoid composition
      of green fruits and reduced beta,beta-xanthophyll accumulation. Natural
      degreening was accompanied by a marked decrease in transcript levels of 1-deoxy-d
      xylulose 5-phosphate synthase (DXS) and geranylgeranyl reductase (CHL P) while,
      conversely, pheophorbide a oxygenase (PaO) and phytoene synthase (PSY) gene
      expression increased. Gibberellin and nitrate delayed the reduction of DXS
      expression and the induction of PaO and PSY transcript accumulation, while no
      differences in CHL P were observed. The data indicate that both ripening
      retardants repressed natural PaO and PSY expression, suggesting a mechanistic
      basis for the elevated levels of chlorophyll and lower carotenoid concentration
      resulting from the gibberellin and nitrogen treatments and the consequent color
      break delay in citrus fruit peels.

PMID- 16787045
TI  - Metabolism by rats of 2-dodecylcyclobutanone, a radiolytic compound present in
      irradiated beef.
AB  - Alkylcyclobutanones (2-ACBs) are suspected cancer promoters and clastogens, which
      have raised concerns about the safety of irradiated foods. Currently there are
      few data on the metabolism of 2-ACBs, which makes it very important to study this
      aspect of 2-ACBs to evaluate their safety. The objectives of this experiment were
      to quantify 2-dodecylcyclobutanone (2-DCB; formed from palmitic acid) in the
      feces and adipose tissue of rats and to check for metabolites of 2-DCB in the
      urine. Six female Sprague-Dawley rats were administered 2-DCB (5 mg/day) in corn
      oil for 5 days via gavage. Six control rats did not receive 2-DCB. Feces and
      urine were collected daily, whereas adipose tissue was collected upon euthanasia.
      Hexane extracts of feces and adipose tissue were analyzed by gas chromatography
      mass spectroscopy (GC-MS). Urine with and without added beta-glucuronidase was
      monitored for glucuronide complexes by hexane extraction and GC-MS. The total
      amount of 2-DCB recovered in feces was 1.78 +/- 0.63 mg at the end of 5 days,
      which represents between 3 and 11% of the total 2-DCB administered. The total
      amount recovered in the adipose tissue was 0.08 +/- 0.01 mg, which was
      approximately 0.33% of the total 2-DCB administered. No metabolites were
      recovered in any of the urine extracts. The results show that at most 11% of the
      2-DCB was recovered unchanged in the feces and adipose tissue. This indicates
      that either most of 2-DCB is metabolized and rapidly eliminated from the body or
      stored at sites other than adipose tissue.

PMID- 16787046
TI  - Fortification of milk with calcium: effect on calcium bioavailability and
      interactions with iron and zinc.
AB  - Calcium solubility, dialysability, and transport and uptake (retention +
      transport) by Caco-2 cells as indicators of calcium bioavailability have been
      estimated in the in vitro gastrointestinal digests of milk and calcium fortified
      milk. A significant linear correlation (p < 0.05) was obtained between calcium
      uptake and the amount of soluble calcium added to the cells, and also between
      percentage calcium uptake and the calcium measured in the analyzed samples. The
      solubility, dialysis, transport, and uptake values are higher (p < 0.05) for
      calcium fortified milks than for nonfortified milks; that is, calcium
      fortification increases not only calcium content but also its bioavailability. An
      inhibitory effect of calcium from fortified milks upon iron absorption was found.
      The observed effect of calcium from fortified milks upon zinc bioavailability
      depends on the in vitro method used, zinc solubility and dialysis decrease in
      calcium fortified milks, and percentage zinc uptake remains unchanged.

PMID- 16787047
TI  - Both soybean and kudzu phytoestrogens modify favorably the blood lipoprotein
      profile in ovariectomized and castrated hamsters.
AB  - The present study compared the hypolipidemic activity of kudzu phytoestrogens
      with that of soybean phytoestrogen in estrogen- and androgen-deficient hamsters.
      In the first experiment, ovariectomized hamsters (n = 37) were randomly divided
      into four groups (n = 9-10 each group). The first group was the control group,
      whereas the second group had the time-releasing estradiol-17beta subcutaneous
      (pellet) implants as a positive control. The third and fourth groups were orally
      administered soybean or kudzu phytoestrogen extracts (30 mg/kg of body weight)
      per day. In the second experiments, the first group of male hamsters (n = 9)
      received a sham operation, whereas the other three groups of male hamsters (n = 9
      each) were castrated. The castrated control group received orally distilled
      water, whereas the second and third castrated groups were orally given 30 mg/kg
      soybean or kudzu phytoestrogen extracts. The results for the first experiment
      showed that the ovariectomized hamsters orally given soybean and kudzu
      phytoestrogen extracts had significantly decreased serum total cholesterol (TC)
      and non-high-density lipoprotein cholesterol (non-HDL-C) with HDL cholesterol
      (HDL-C) being unaffected. The data from the second experiment demonstrated that
      administration of soybean but not kudzu phytoestrogen extracts decreased
      significantly serum TC. However, administration of kudzu phytoestrogens caused
      redistribution of cholesterol among lipoproteins, leading to a significant
      decrease in the ratio of non-HDL-C to HDL-C. It was concluded that both soybean
      and kudzu phytoestrogens could modify favorably lipoprotein profiles in
      ovariectomized and castrated hamsters.

PMID- 16787048
TI  - The flavonol quercetin-3-glucoside inhibits cyanidin-3-glucoside absorption in
      vitro.
AB  - At present, little is known about the mechanisms responsible for intestinal
      absorption of anthocyanins (ACNs). For example, it has not yet been established
      if ACNs are absorbed through an active transport mechanism, such as the sodium
      dependent glucose transporter (SGLT1), or by passive diffusion. Previously, we
      found that the absorption of ACNs differs between regions of the digestive tract
      and is maximal in the jejunum, suggesting that an active transport mechanism is
      involved. In the present study, we examined the effect of d-glucose (main
      substrate of SGLT1), phloridzin (inhibitor of SGLT1), and quercetin-3-glucose
      (Q3G, a flavonol) on the absorption of cyanidin-3-glucoside (C3G; approximately 5
      micromol/L) by mouse jejunum mounted in Ussing chambers. We found that the
      presence of either D-glucose (10, 20, and 40 mmol/L) or phloridzin (50, 100, and
      200 micromol/L) resulted in a small but insignificant inhibition of C3G
      disappearance from the mucosal solution (decrease of disappearance with glucose,
      33%; with phloridzin, 18%; NS). However, when the flavonol Q3G (50 micromol/L)
      was added to the mucosal solution together with the C3G, the disappearance of C3G
      was significantly decreased (74%; p < 0.001), and Q3G disappeared instead. In
      addition, we found phloretin and quercetin, the aglycones of phloridzin and Q3G,
      respectively, present in the mucosal solution and tissue extracts, indicating
      hydrolysis of these compounds by the enterocytes of the jejunum. In contrast, the
      aglycone cyanidin was not detected at all. Our results show that in the mouse
      small intestine, ACN absorption is not solely dependent on the activity of the
      SGLT1 transporter, as d-glucose and phloridzin had only a slight effect on
      uptake. Q3G, however, clearly inhibited C3G disappearance. These results suggest
      that there might be a competitive inhibition between C3G and Q3G absorption. It
      is possible that an absorption mechanism other than the SGLT1 is involved, which
      has a structural preference toward flavonols.

PMID- 16787050
TI  - Cooperative 4-pyridone H-bonds with extraordinary stability. A DFT molecular
      orbital study.
AB  - The N-H...O H-bonding enthalpy between 4-pyridones connected in a chain of H
      bonds can achieve 23 kcal/mol for the most central H-bonds, while that between
      two 4-pyridones is 9.90 kcal/mol based upon DFT calculations on the counterpoise
      corrected potential energy surfaces. That the range of enthalpies for N-H...O H
      bonds can vary from as little as 2 to as much 23 kcal/mol depends primarily upon
      the polarizability of whatever internally connects the N-H and C=O within the H
      bonding molecule, which are two parallel -C=C- entities in 4-pyridone. The
      contribution of covalent or charge-transfer interactions between the pi-systems
      of adjacent 4-pyridones is small.

PMID- 16787049
TI  - The organization of aromatic side groups in an amyloid fibril probed by solid
      state 2H and 19F NMR spectroscopy.
AB  - Some 25 diseases are associated with proteins and peptides that assemble into
      amyloid fibrils composed of beta-strands connected by hydrogen bonds oriented
      parallel to the fiber long axis. There is mounting evidence that amyloid
      formation involves specific interactions between amino acid side groups, which
      bring together beta-sheets to form layers with buried and exposed faces. This
      work demonstrates how a combination of solid-state 2H and 19F NMR experiments can
      provide constraints on fibril architecture by probing the environment and spatial
      organisation of aromatic side groups. It is shown that phenylalanine rings within
      fibrils formed by a decapeptide fragment of the islet amyloid polypeptide,
      amylin, are highly motionally restrained and are situated within 6.5 A of one
      another. Taken together with existing structural constraints for this peptide,
      these results are consistent with a fibril architecture that comprises layers of
      two or more beta-sheets, with the aromatic residues facing into the inter-sheet
      space and possibly engaged in pi-pi interactions. The methods presented will be
      of general utility in exploring the architecture of fibrils of larger, full
      length peptides and proteins, including amylin itself.

PMID- 16787051
TI  - A monolithiated and its related 1,3-dilithiated allylsilane: syntheses, crystal
      structures, and reactivity.
AB  - Treatment of Me2Si(CH2CH=CH2)(CH2NC5H10) with 1 or 2 equiv of t-BuLi afforded the
      mono- or dilithiated allylsilanes, which crystallize as a tetramer and a hexamer
      from pentane. The product selectivity in trapping reactions is influenced by the
      ability of both the solvent and the electrophile to coordinate the lithium
      center.

PMID- 16787052
TI  - Determination of lysine pK values using [5-13C]lysine: application to the lyase
      domain of DNA Pol beta.
AB  - Determination of the protonation state of titratable protein residues is of
      critical importance for the interpretation of active site chemistry, as well as
      for understanding the role of electrostatic interactions in protein folding and
      stability. However, protein titration studies are limited by the fact that, at
      extreme pH values, increasing fractions of unfolded or partially unfolded
      structures may be present. This problem is particularly acute for lysine residues
      which have high pK values. In the present study, we point out that the use of the
      13C resonance of lysine C-5 as a reporter for titration of the epsilon-amino
      group is preferable to the use of C-6 due to the 5-fold greater titration shift,
      so that reasonable results can be obtained using a two parameter fit of data
      obtained over a more limited pH range. A new synthetic procedure for [5
      13C]lysine is described, and the pK value for Lys72 in the lyase domain of DNA
      polymerase beta has been determined using the [5-13C]lysine-labeled enzyme. The
      results agree well with recent studies of the Pol lambda lyase domain,
      demonstrating that the pK value for this residue is not optimized for Schiff base
      chemistry (Gao et al., Biochemistry 2006, 45, 1785-1794). We also have re
      evaluated data for the pK of Lys73 in the TEM-1 beta-lactamase.

PMID- 16787053
TI  - To patterned binary polymer brushes via capillary force lithography and surface
      initiated polymerization.
AB  - An effective approach is described for the synthesis of binary patterned polymer
      brushes using a combination of capillary force lithography and surface-initiated
      polymerization. First, the approach calls for an ultrathin polystyrene (PS) mask
      to be deposited, in a pattern, over a surface to which a layer of polymerization
      initiator has already been anchored. Next, surface-initiated atom transfer
      radical polymerization (ATRP) is performed. This can graft the initial polymer
      brush onto those areas of the surface unprotected by the PS mask. After grafting
      is complete, the PS mask is removed and a second brush is synthesized on the
      newly exposed areas.

PMID- 16787054
TI  - Enhanced open-circuit voltage in subphthalocyanine/C60 organic photovoltaic
      cells.
AB  - A double-heterostructure boron subphthalocyanine chloride (SubPc)/C60 thin-film
      photovoltaic cell exhibits a more than doubled Voc compared to a conventional
      copper phthalocyanine (CuPc)/C60 cell under 1 sun AM1.5G simulated illumination.
      The lower oxidation potential of SubPc results in an increase in the energy
      difference between the lowest unoccupied molecular orbital of the acceptor-like
      material and the highest occupied molecular orbital of the donor-like material
      (referred to as the interface gap, Ig) by 400 meV. We attribute the significant
      increase in Voc to this increase in Ig.

PMID- 16787055
TI  - Off-resonance TROSY-selected R 1rho experiment with improved sensitivity for
      medium- and high-molecular-weight proteins.
AB  - NMR spin relaxation techniques that utilize relaxation interference phenomena
      (TROSY) enable chemical exchange processes to be characterized in high-molecular
      weight proteins. A TROSY-selected (TS) approach for measuring off-resonance R1rho
      relaxation in the spin-locked rotating reference frame is developed using three
      principles: (i) deuteration of nonexchangeable 1H sites to minimize remote dipole
      dipole interactions, (ii) selective excitation of the slowly relaxing 15N doublet
      component to obtain optimal initial conditions, and (iii) selective inversion of
      one of the 15N doublet components to suppress cross-relaxation during the spin
      lock period. The method is validated using [90%-15N, 70%-2H] ubiquitin at 280 K.
      The TROSY-selected R1rho experiment enables characterization of backbone dynamics
      on the microsecond time scale in large proteins.

PMID- 16787056
TI  - Reciprocity of steric and stereoelectronic effects in the collagen triple helix.
AB  - In previous work, we demonstrated that 4-fluoroproline residues can contribute
      greatly to the conformational stability of the collagen triple helix, and that
      this stability arises from stereoelectronic effects that fix the pucker of the
      pyrrolidine ring and thereby preorganize the backbone properly for triple-helix
      formation. Here, we take a reciprocal approach, demonstrating that the steric
      effect of a 4-methyl group confers stability similar to that from a 4-fluoro
      group in the opposite configuration. Such fundamental interplay between steric
      and stereoelectronic effects is heretofore unknown in proteins-natural or
      synthetic-and provides a new means to modulate conformational stability.

PMID- 16787057
TI  - Transition state stabilization and alpha-amino carbon acidity in alanine
      racemase.
AB  - Combined QM/MM simulations have been carried out to investigate the origin of the
      carbon acidity enhancement in the alanine racemization reaction catalyzed by
      alanine racemase (AlaR). The present studies show that enhancement of carbon
      acidity of alpha-amino acids by cofactor pyridoxal 5'-phosphate, PLP, with an
      unusual, unprotonated pyridine is due to solvation effects, in contrast to the
      intrinsic electron-withdrawing stabilization by the pyridinium ion to form a
      quinonoid intermediate. Alanine racemase further lowers the alpha-proton acidity
      and provides an overall 14-17 kcal/mol transition state stabilization. Our
      computational results are consistent with the hypothesis that the use of the
      unusual form of PLP cofactor in AlaR is to raise the free energy of the
      intermediate, thereby increasing the reprotonation rate and enhancing the enzyme
      selectivity for racemization.

PMID- 16787058
TI  - Confinement and controlled release of bisphosphonates on ordered mesoporous
      silica-based materials.
AB  - Bisphosphonates have been confined in siliceous ordered mesoporous materials, and
      the drug release rate of these systems has been investigated. The bisphosphonate
      adsorption rate has been increased from 1% in oral administration to around 40%
      locally delivered. Drug dosage can be modulated through amine modification of the
      material surface, leading to a bisphosphonate adsorption in the ordered
      mesoporous matrices 3 times larger than that for unmodified materials. The use of
      these drug delivery systems opens new fields with new possibilities for tissue
      engineering.

PMID- 16787059
TI  - Distance distributions of short polypeptides recovered by fluorescence resonance
      energy transfer in the 10 A domain.
AB  - Fluorescence resonance energy transfer (FRET) between tryptophan (Trp) as donor
      and 2,3-diazabicyclo[2.2.2]oct-2-ene (Dbo) as acceptor was studied by steady
      state and time-resolved fluorescence spectroscopy. The unique feature of this
      FRET pair is its exceptionally short Forster radius (10 A), which allows one to
      recover distance distributions in very short structureless peptides. The
      technique was applied to Trp-(GlySer)n-Dbo-NH2 peptides with n = 0-10, for which
      the average probe/quencher distance ranged between 8.7 and 13.7 A experimentally
      (in propylene glycol, analysis according to wormlike chain model) and 8.6-10.2 A
      theoretically (for n = 0-6, GROMOS96 molecular dynamics simulations). The larger
      FRET efficiency in steady-state compared to time-resolved fluorescence
      experiments was attributed to a static quenching component, suggesting that a
      small but significant part (ca. 10%) of the conformations are already in van der
      Waals contact when excitation occurs.

PMID- 16787060
TI  - A modular approach to ferroelectric polymers with chemically tunable curie
      temperatures and dielectric constants.
AB  - We present a modular approach toward poly(vinylidene fluoride)-based
      ferroelectric fluoropolymers with high dielectric constants. This strategy is
      based on a two-step reaction, including the copolymerization of vinylidene
      fluoride and chlorotrifluoroethylene and a subsequent hydrogenation reaction. The
      chemical structures and compositions of the resulting polymers can be precisely
      controlled, leading to tunable Curie temperatures and dielectric constants and a
      systematical study of structure-property correlations.

PMID- 16787061
TI  - Self-assembling bisurea macrocycles used as an organic zeolite for a highly
      stereoselective photodimerization of 2-cyclohexenone.
AB  - We report a highly selective 2 + 2 cycloaddition of 2-cyclohexenone in the
      presence of self-assembled bisurea macrocycles that yields the head-to-tail
      photodimer. The reaction proceeds with high conversion and with decreased
      incidence of secondary photorearrangement. Furthermore, the product can be
      extracted from the assembly, and the solid assembly is readily recovered and
      reused, much like a zeolite.

PMID- 16787062
TI  - Hydrogenation of carbon monoxide by tetranuclear rare earth metal polyhydrido
      complexes. Selective formation of ethylene and isolation of well-defined polyoxo
      rare earth metal clusters.
AB  - The reaction of the tetranuclear rare earth metal polyhydrido complexes {Cp'Ln(mu
      H)2}4(THF) (Cp' = C5Me4SiMe3, Ln = Y (1a), Lu (1b)) with carbon monoxide (1 atm)
      yielded ethylene and the corresponding tetraoxo cubane complexes (Cp'Ln)4(mu3-O)4
      (Ln = Y (5a), Lu (5b)). Stepwise formation of some key reaction intermediates,
      such as oxymethylene complexes (Cp'Ln)4(mu-OCH2)(mu-H)6(THF) (Ln = Y (2a), Lu
      (2b)), enolate species (Cp'Y)4(OCH=CH2)(mu-O)(mu-H)5(THF) (3), and dioxo complex
      (Cp'Y)4(mu3-O)2(mu-H)4(THF) (4), was confirmed. The molecular structures of 2a,
      4, and 5b were determined by X-ray diffraction studies.

PMID- 16787063
TI  - Total synthesis and absolute stereochemical assignment of (+)- and (-)
      galbulimima alkaloid 13.
AB  - We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13. The
      absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is revised to 2S.
      Sequential use of catalytic cross-coupling and cross-metathesis reactions
      followed by an intramolecular Diels-Alder reaction provided the required trans
      decalin AB-ring system and masked the C16 carbonyl as an N-vinyl carbamate for
      late-stage unveiling in the form of the necessary C16 enone. A vinyl radical
      cyclization secured the C-ring, while successful execution of our strategy for
      introduction of the CDE-ring system in complex galbulimima alkaloids provided the
      target pentacycle with complete diastereoselection.

PMID- 16787064
TI  - Geosmin biosynthesis. Streptomyces coelicolor germacradienol/germacrene D
      synthase converts farnesyl diphosphate to geosmin.
AB  - Geosmin is responsible for the characteristic odor of moist soil. Incubation of
      recombinant germacradienol synthase, encoded by the SCO6073 (SC9B1.20) gene of
      the Gram-positive soil bacterium Streptomyces coelicolor, with farnesyl
      diphosphate (2, FPP) in the presence of Mg2+ gave a mixture of (4S,7R)-germacra
      1(10)E,5E-diene-11-ol (3) (74%), (-)-(7S)-germacrene D (4) (10%), geosmin (1)
      (13%), and a hydrocarbon, tentatively assigned the structure of octalin 5 (3%).
      Individual incubations of recombinant germacradienol synthase with [1,1-2H2]FPP
      (2a), (1R)-[1-2H]-FPP (2b), and (1S)-[1-2H]-FPP (2c), as well as with FPP (2) in
      D2O, and GC-MS analysis of the resulting deuterated products supported a
      mechanism of geosmin formation involving proton-initiated cyclization and retro
      Prins fragmentation of the initially formed germacradienol to give intermediate
      5, followed by protonation of 5, 1,2-hydride shift, and capture of water.

PMID- 16787065
TI  - Chiral permselectivity in surface-modified nanoporous opal films.
AB  - Nanoporous 7 mum thin opal films comprising 35 layers of 200 nm diameter SiO2
      spheres were assembled on Pt electrodes and modified with chiral selector
      moieties on the silica surface. Diffusion of chiral redox species through the
      opals was studied by cyclic voltammetry. The chiral opal films demonstrate high
      selectivity for transport of one enantiomer over the other. This chiral
      permselectivity is attributed to the surface-facilitated transport utilizing
      noncovalent interactions between the chiral permeant molecules and surface-bound
      chiral selectors.

PMID- 16787067
TI  - Tropene derivatives by sequential intermolecular and transannular, intramolecular
      palladium-catalyzed hydroamination of cycloheptatriene.
AB  - A consecutive inter- and intramolecular hydroamination of cycloheptatriene with
      primary aromatic amines, benzylic amines, and beta-phenethylamines occurs to
      produce pharmaceutically relevant tropene (8-azabicyclo[3.2.1]octene) frameworks
      in good to excellent yields. This reaction occurs in the presence of a catalyst
      generated from palladium trifluoroacetate, 9,9-dimethyl-4,5
      bis(diphenylphosphino)xanthene and a mild acid. Mechanistic studies reveal that
      the overall process has some reversible steps, but that the rate of these reverse
      reactions are far slower than the rates of the forward catalytic process.

PMID- 16787066
TI  - Gold(I)-catalyzed synthesis of dihydropyrans.
AB  - A trinuclear gold(I)-oxo complex, [(Ph3PAu)3O]BF4, serves as the catalyst for the
      stereocontrolled synthesis of 2-hydroxy-3,6-dihydropyrans from propargyl vinyl
      ethers. Importantly, the rearrangement proceeds with excellent
      diastereoselectivity, and the rearrangement of chiral nonracemic propargyl vinyl
      ethers proceeds with excellent chirality transfer to furnish enantioenriched
      pyrans. Additionally, the reaction is amenable to the synthesis of spiroketals
      from appropriately functionalized precursors. In this case, from a linear
      precursor, in a single step, the bicyclic spiroketal framework is established
      with complete stereocontrol over three centers and an alkene functional group in
      the product.

PMID- 16787068
TI  - Hydrogen storage in metal-organic frameworks by bridged hydrogen spillover.
AB  - The possible utilization of hydrogen as the energy source for fuel-cell vehicles
      is limited by the lack of a viable hydrogen storage system. Metal-organic
      frameworks (MOFs) belong to a new class of microporous materials that have
      recently been shown to be potential candidates for hydrogen storage; however, no
      significant hydrogen storage capacity has been achieved in MOFs at ambient
      temperature. Here we report substantially increased hydrogen storage capacities
      of modified MOFs by using a simple technique that causes and facilitates hydrogen
      spillover. Thus, the storage of 4 wt % is achieved at room temperature and 100
      atm for the modified IRMOF-8. The adsorption is reversible, and the rates are
      fast. That has made MOFs truly promising for hydrogen storage application.

PMID- 16787069
TI  - Synthesis of mixed sequence borane phosphonate DNA.
AB  - A novel solid-phase phosphoramidite-based method has been developed for the
      synthesis of borane phosphonate DNA. Keys to this new approach are replacement of
      the common 5'-dimethoxytrityl blocking group with a 5'-silyl ether and the use of
      new protecting groups on the bases (adenine, N6-dimethoxytrityl; cytosine, N4
      trimethoxytrityl; guanine, N2-[9-fluorenylmethoxycarbonyl]; thymine, N3-anisoyl).
      Because of these developments, it is now possible for the first time to
      synthesize oligodeoxynucleotides having any combination of the four 2'
      deoxynucleosides and both phosphate and borane phosphonate internucleotide
      linkages (including oligomers having exclusively borane phosphonate linkages).

PMID- 16787070
TI  - Most stable metallic phase of the mixed-valence MMX-chain, Pt2(dtp)4I (dtp =
      C2H5CS2-), in purely d-electronic conductors based on the transition-metal
      complex.
AB  - The electrical resistivity and X-ray oscillation photograph measurements for an
      MMX-chain complex, Pt2(dtp)4I (dtp = C2H5CS2-), under high pressure were
      performed. We observed the most stable metallic phase (TMI = 70 K, under 2.2 GPa)
      in the 1-D purely d-electronic conductors and pressure-induced metal-insulator
      transition including the structural phase transition at 3.0 GPa.

PMID- 16787072
TI  - Backbone-thermoresponsive hyperbranched polyethers.
AB  - A new type of materials, the backbone-thermoresponsive hyperbranched polyether,
      was successfully synthesized by proton-transfer polymerization of 1,4-butanediol
      diglycidyl ether and various triols, and the lower critical solution temperature
      (LCST) values can be readily adjusted from 19.0 to 40.3 degrees C by changing the
      hydrophilic/hydrophobic balance of BDE and triols.

PMID- 16787071
TI  - Regiochemical control in the metal-catalyzed transposition of allylic silyl
      ethers.
AB  - A novel mode of regiochemical control over the allylic [1,3]-transposition of
      silyloxy groups catalyzed by Re2O7 has been developed. This strategy relies on a
      cis-oriented vinyl boronate, generated from the Alder-ene reaction of homoallylic
      silyl ethers and alkynyl boronates, to trap out the allylic hydroxyl group. The
      resulting cyclic boronic acids are excellent partners for cross-coupling
      reactions. High chirality transfer is observed for the rearrangement of
      enantioenriched allylic silyl ethers.

PMID- 16787073
TI  - Hydroheteroarylation of alkynes under mild nickel catalysis.
AB  - Nickel complexes having a bulky tri(sec-alkyl)phosphine ligand catalyze
      hydroheteroarylation of alkynes at 35 degrees C. Selective activation of an Ar-H
      bond over an Ar-CN bond of N-protected 3-cyanoindoles is achieved by a proper
      choice of ligand and/or an N-protecting group. The catalysis is applicable to a
      diverse range of heteroarenes to afford cis-hydroheteroarylation products in
      highly chemo- and stereoselective manners. Excellent regioselectivity is observed
      with unsymmetrical alkynes to give the corresponding heteroaryl-substituted
      ethenes having a larger substituent trans to an aryl group.

PMID- 16787074
TI  - Germanium telluride nanowires and nanohelices with memory-switching behavior.
AB  - We report the synthesis of single-crystalline GeTe nanowires (NWs) and
      nanohelices (NHs) using a vapor transport method assisted by metal catalysts. The
      NWs have typical diameters of 65 +/- 20 nm and lengths reaching up to 50 mum,
      while NHs have an average helix diameter of 135 +/- 30 nm, with widely varying
      pitches. Electron microscopy and diffraction measurements show that these NWs and
      NHs are single crystalline and exhibit a rhombohedral structure. The devices
      incorporating individual GeTe NWs exhibit nonvolatile resistance changes
      associated with voltage-driven crystalline-amorphous transitions, suggesting that
      these NWs can be the basis of an electrically driven nonvolatile memory.

PMID- 16787075
TI  - Palladium-catalyzed coupling of allylboronic acids with iodobenzenes. Selective
      formation of the branched allylic product in the absence of directing groups.
AB  - Palladium-catalyzed coupling reactions of functionalized allylboronic acids with
      iodobenzenes were achieved under standard Suzuki-Miyaura coupling conditions. The
      coupling reactions afforded selectively the branched allylic products in high to
      excellent yields. In contrast to palladium-catalyzed nucleophilic substitution
      reactions proceeding via (eta3-allyl)palladium intermediates, this process does
      not require directing groups in the allyl moiety to achieve substitution at the
      congested allylic terminus. The regioselectivity of the process was largely
      unaffected by the substituent effects of the iodobenzenes and the allylic
      substrates.

PMID- 16787076
TI  - Rh(I)-catalyzed silylation of aryl and alkenyl cyanides involving the cleavage of
      C-C and Si-Si bonds.
AB  - The Rh(I)-catalyzed silylation of nitriles with disilanes is described. The
      cleavage of inert carbon-cyano and silicon-silicon bonds occurs in this
      catalysis.

PMID- 16787077
TI  - Potentiometry at trace levels in confined samples: ion-selective electrodes with
      subfemtomole detection limits.
AB  - We explore here for the first time the direct potentiometric detectability of
      calcium, lead, and silver ions in amounts on the order of 300 attomoles at 100
      picomolar concentrations without any preconcentration, analyte recycling, or
      electrocatalytic signal enhancement. The results presented here place zero
      current potentiometry among the most sensitive electrochemical methods available.

PMID- 16787079
TI  - High performance poly(styrene-b-diene-b-styrene) triblock copolymers from a
      hydrocarbon-soluble and additive-free dicarbanionic initiator.
AB  - A new hydrocarbon-soluble (additive-free) dicarbanionic organolithium initiator,
      obtained by a simple halogen-lithium exchange reaction (Gilman's reaction) from a
      diarylhalide containing a side C15 alkyl chain, has been designed and used to
      initiate the anionic polymerization of butadiene and styrene. The dilithiated
      species formed afford well-defined poly(styrene-b-butadiene-b-styrene) (SBS)
      triblock copolymers with a high percentage of 1,4-microstructure polybutadiene
      (91%) and excellent mechanical properties, such as ultimate tensile strength
      higher than 30 MPa and elongation at a break of 1000%. This represents a
      breakthrough in the synthesis of SBS polymers, one of the most used thermoplastic
      elastomers.

PMID- 16787078
TI  - Asymmetric Friedel-crafts reaction of indoles with imines by an organic catalyst.
AB  - In this communication, we report an asymmetric Friedel-Crafts reaction of indoles
      with imines catalyzed by a bifunctional cinchona alkaloid catalyst. This is the
      first efficient organocatalytic asymmetric Friedel-Crafts reaction of indoles
      with imines. This reaction is operationally simple and, unprecedentedly, affords
      high enantioselectivity for a wide range of indoles and both aryl and alkyl
      imines. This establishes a direct, convergent, and versatile approach to
      optically active 3-indolyl methanamines, a structural motif embedded in numerous
      indole alkaloids and synthetic indole derivatives.

PMID- 16787080
TI  - Enantioselective synthesis of bridged- or fused-ring bicyclic ketones by a
      catalytic asymmetric Michael addition pathway.
AB  - Efficient methodology has been developed for the conjugate addition of ketene
      acetals to cyclic alpha,beta-enones. The chiral adducts allow access to fused- or
      bridged-ring structures such as those shown.

PMID- 16787081
TI  - Nonchelated d0 zirconium-alkoxide-alkene complexes.
AB  - The reaction of Cp'2Zr(O(t)Bu)Me (Cp' = C5H4Me) and [Ph3C][B(C6F5)4] yields the
      base-free complex [Cp'2Zr(O(t)Bu)][B(C6F5)4] (6), which exists as
      Cp'2Zr(O(t)Bu)(ClR)+ halocarbon adducts in CD2Cl2 or C6D5Cl solution. Addition of
      alkenes to 6 in CD2Cl2 solution at low temperature gives equilibrium mixtures of
      Cp'2Zr(O(t)Bu)(alkene)+ (12a-l), 6, and free alkene. The NMR data for 12a-l are
      consistent with unsymmetrical alkene bonding and polarization of the alkene C=C
      bond with positive charge buildup at C(int) and negative charge buildup at
      C(term). These features arise due to the lack of d-pi* back-bonding. Equilibrium
      constants for alkene coordination to 6 in CD2Cl2 at -89 degrees C, K(eq) =
      [12][6](-1)[alkene](-1), vary in the order: vinylferrocene (4800 M(-1)) >>
      ethylene (7.0) approximately alpha-olefins > cis-2-butene (2.2) > trans-2-butene
      (<0.1). Alkene coordination is inhibited by sterically bulky substituents on the
      alkene but is greatly enhanced by electron-donating groups and the beta-Si
      effect. Compounds 12a-l undergo two dynamic processes: reversible alkene
      decomplexation via associative substitution of a CD2Cl2 molecule, and rapid
      rotation of the alkene around the metal-(alkene centroid) axis.

PMID- 16787082
TI  - Trehalose click polymers inhibit nanoparticle aggregation and promote pDNA
      delivery in serum.
AB  - Herein, three new glycopolymers have been synthesized via "click polymerization"
      to promote nucleic acid delivery in the presence of biological media containing
      serum. These structures were designed to contain a trehalose moiety to promote
      biocompatibility, water solubility, and stability against aggregation, amide
      triazole groups to enhance DNA binding affinity, and an oligoamine unit to
      facilitate DNA encapsulation, phosphate neutralization, and interactions with
      cell surfaces. A 2,3,4,2',3',4'-hexa-O-acetyl-6,6'-diazido-6,6'-dideoxy-D
      trehalose (4) monomer was polymerized via copper(I)-catalyzed azide-alkyne
      cycloaddition with a series of dialkyne-amide comonomers that contain either one,
      two, or three Boc-protected secondary amines (7a, 7b, or 7c, respectively). After
      deprotection, three water-soluble polycations (9a, 9b, or 9c) were obtained with
      similar degrees of polymerization (n = 56-61) to elucidate the role of amine
      number on nucleic acid binding, complex formation, stability, and cellular
      delivery. Gel electrophoresis and ethidium bromide experiments showed that 9a-9c
      associated with plasmid DNA (pDNA) and formed complexes (polyplexes) at N/P
      ratios dependent on the amine number. TEM experiments revealed that 9a-9c
      polyplexes were small (50-120 nm) and had morphologies (spherical and rodlike)
      associated with the polymer chain stiffness. Dynamic light scattering studies in
      the presence of media containing serum demonstrated that 9c polyplexes had a low
      degree of flocculation, whereas 9a and 9b polyplexesd aggregate rapidly. Further
      biological studies revealed that these structures were biocompatible and deliver
      pDNA into HeLa cells. Particularly, 9c polyplexes promoted high delivery efficacy
      and gene expression profiles in the presence of serum.

PMID- 16787083
TI  - Two-state reactivity, electromerism, tautomerism, and "surprise" isomers in the
      formation of compound II of the enzyme horseradish peroxidase from the principal
      species, compound I.
AB  - QM and QM/MM calculations on Compound II, the enigmatic species in the catalytic
      cycle of the horseradish peroxidase enzyme, reveal six low-lying isomers. The
      principal isomer is the triplet oxo-ferryl form (PorFe(IV)=O) that yields the
      hydroxo-ferryl isomer (PorFe(IV)-OH+). These are the only forms observed in
      experimental studies. Theory shows, however, that these are the least stable
      isomers of Compound II. The two most stable forms are the singlet and triplet
      states of the Por+*Fe(III)-OH electromer. In addition, theory reveals species
      never considered in heme enzymes: the singlet and triplet states of the
      Por+*Fe(III)-OH2 electromer. The computational results reproduce the experimental
      features of the known isomers and enable us to draw relationships and make
      predictions regarding the missing ones. For example, while the "surprise"
      species, singlet and triplet Por+*Fe(III)-OH2, have never been considered in heme
      chemistry, the calculated Fe-O bond lengths indicate that these isomers may have,
      in fact, been observed in one of the two opposing EXAFS studies reported
      previously. Furthermore, these ferric-aqua complexes could be responsible for the
      reported 18O exchange with bulk water. It is clear, therefore, that the role of
      Compound II in the HRP cycle is considerably more multi-faceted than has been
      revealed so far. Our suggested multi-state reactivity scheme provides a paradigm
      for Compound II species. The calculated Mossbauer parameters may be helpful
      toward eventual characterization of these missing isomers of Compound II.

PMID- 16787084
TI  - Solid-state acid-base interactions in complexes of heterocyclic bases with
      dicarboxylic acids: crystallography, hydrogen bond analysis, and 15N NMR
      spectroscopy.
AB  - A cancer candidate, compound 1, is a weak base with two heterocyclic basic
      nitrogens and five hydrogen-bonding functional groups, and is sparingly soluble
      in water rendering it unsuitable for pharmaceutical development. The crystalline
      acid-base pairs of 1, collectively termed solid acid-base complexes, provide
      significant increases in the solubility and bioavailability compared to the free
      base, 1. Three dicarboxylic acid-base complexes, sesquisuccinate 2, dimalonate 3,
      and dimaleate 4, show the most favorable physicochemical profiles and are studied
      in greater detail. The structural analyses of the three complexes using crystal
      structure and solid-state NMR reveal that the proton-transfer behavior in these
      organic acid-base complexes vary successively correlating with Delta pKa. As a
      result, 2 is a neutral complex, 3 is a mixed ionic and zwitterionic complex and 4
      is an ionic salt. The addition of the acidic components leads to maximized
      hydrogen bond interactions forming extended three-dimensional networks. Although
      structurally similar, the packing arrangements of the three complexes are
      considerably different due to the presence of multiple functional groups and the
      flexible backbone of 1. The findings in this study provide insight into the
      structural characteristics of complexes involving heterocyclic bases and
      carboxylic acids, and demonstrate that X-ray crystallography and 15N solid-state
      NMR are truly complementary in elucidating hydrogen bonding interactions and the
      degree of proton transfer of these complexes.

PMID- 16787085
TI  - Perturbation of conjugation in internally solvated allylic lithium compounds:
      variation of ligand structure. NMR and X-ray crystallography.
AB  - Several allyic lithium compounds were prepared with different potential ligands
      tethered at C2. These are with CH3OCH2CH2NCH3CH2-, 5 and 1-TMS 6, with
      (CH3)2NCH2CH2NCH3CH2-, 1-TMS 7, and with ((CH3)2NCH2CH2)2NCH2-, 8 and 1-TMS 9. In
      all these compounds Li is fully coordinated to the pendant ligand and is sited
      off the axis perpendicular to the allyl plane at one of the allyl termini as
      indicated by a combination of X-ray crystallography and NMR spectra. Compounds 5
      and 8 are Li-bridged dimers as shown by X-ray crystallography and also dimeric in
      benzene solution as determined from freezing point determinations. Compounds 6,
      7, and 9 are monomeric in THF-d8 or diethyl ether-d10 solution and exhibit one
      bond 13C1, 6Li scalar coupling at low temperature. Taken together the
      crystallographic and NMR data indicate that all of these compounds incorporate
      partially delocalized allylic moieties. Compounds 5 and 8 undergo fast 1,3-Li
      sigmatropic shifts that are proposed to take place within low concentrations of
      monomers in fast equilibrium with prevalent dimers. Averaging with increasing
      temperature of the one-bond 13C, 6Li coupling constant in 6, 7, and 13 provided
      the dynamics of bimolecular C-Li exchange with Delta H++ values of 6.7, 12, and
      13 kcal x mol(-1), respectively. Averaging of the diastereotopic N(CH3)2 13C
      resonances of 7 is indicative of fast transfer of coordinated ligand between
      faces of the allyl plane Delta H++ = 5.3 kcal x mol(-1) combined with slower
      inversion at nitrogen. Compound 8 exhibits similar effects. It is concluded that
      variation of the ligand structure changes dynamic behavior of the compounds but
      has little influence of their degrees of delocalization.

PMID- 16787086
TI  - Size- and shape-dependent transformation of nanosized titanate into analogous
      anatase titania nanostructures.
AB  - A size- and shape-dependent morphological transformation was demonstrated during
      the hydrothermal soft chemical transformation, in neutral solution, of titanate
      nanostructures into their anatase titania counterparts. Specifically,
      lepidocrocite hydrogen titanate nanotubes with diameters of approximately 10 nm
      were transformed into anatase nanoparticles with an average size of 12 nm.
      Lepidocrocite hydrogen titanate nanowires with relatively small diameters
      (average diameter range of < or = 200 nm) were converted into single-crystalline
      anatase nanowires with relatively smooth surfaces. Larger diameter (>200 nm)
      titanate wires were transformed into analogous anatase submicron wire motifs,
      resembling clusters of adjoining anatase nanocrystals with perfectly parallel,
      oriented fringes. Our results indicate that as-synthesized TiO2 nanostructures
      possessed higher photocatalytic activity than the commercial titania precursors
      from whence they were derived.

PMID- 16787087
TI  - Temperature- and length-dependent energetics of formation for polyalanine helices
      in water: assignment of w(Ala)(n,T) and temperature-dependent CD ellipticity
      standards.
AB  - Length-dependent helical propensities w(Ala)(n,T) at T = 10, 25, and 60 degrees C
      are assigned from t/c values and NMR 13C chemical shifts for series 1 peptides
      TrpLys(m)Inp2(t)Leu-Ala(n)(t)LeuInp2Lys(m)NH2, n = 15, 19, and 25, m = 5, in
      water. Van't Hoff analysis of w(Ala)(n,T) show that alpha-helix formation is
      primarily enthalpy-driven. For series 2 peptides Ac-Trp Lys5Inp2(t)Leu
      (beta)AspHel-Ala(n)-beta-(t)LeuInp2Lys5NH2, n = 12 and 22, which contain
      exceptionally helical Ala(n) cores, protection factor-derived fractional
      helicities FH are assigned in the range 10-30 degrees C in water and used to
      calibrate temperature-dependent CD ellipticities [theta](lambda,H,n,T). These are
      applied to CD data for series 1 peptides, 12 < or = n < or = 45, to confirm the
      w(Ala)(n,T) assignments at T = 25 and 60 degrees C. The [theta](lambda,H,n,T) are
      temperature dependent within the wavelength region, 222 +/- 12 nm, and yield a
      temperature correction for calculation of FH from experimental values of
      [theta](222,n,T,Exp).

PMID- 16787088
TI  - Toward exceeding the Shockley-Queisser limit: photoinduced interfacial charge
      transfer processes that store energy in excess of the equilibrated excited state.
AB  - Nanocrystalline (anatase), mesoporous TiO2 thin films were functionalized with
      [Ru(bpy)2(deebq)](PF6)2, [Ru(bq)2(deeb)](PF6)2, [Ru(deebq)2(bpy)](PF6)2,
      [Ru(bpy)(deebq)(NCS)2], or [Os(bpy)2(deebq)](PF6)2, where bpy is 2,2'-bipyridine,
      bq is 2,2'-biquinoline, and deeb and deebq are 4,4'-diethylester derivatives.
      These compounds bind to the nanocrystalline TiO2 films in their carboxylate forms
      with limiting surface coverages of 8 (+/- 2) x 10(-8) mol/cm2. Electrochemical
      measurements show that the first reduction of these compounds (-0.70 V vs SCE)
      occurs prior to TiO2 reduction. Steady state illumination in the presence of the
      sacrificial electron donor triethylamine leads to the appearance of the reduced
      sensitizer. The thermally equilibrated metal-to-ligand charge-transfer excited
      state and the reduced form of these compounds do not inject electrons into TiO2.
      Nanosecond transient absorption measurements demonstrate the formation of an
      extremely long-lived charge separated state based on equal concentrations of the
      reduced and oxidized compounds. The results are consistent with a mechanism of
      ultrafast excited-state injection into TiO2 followed by interfacial electron
      transfer to a ground-state compound. The quantum yield for this process was found
      to increase with excitation energy, a behavior attributed to stronger overlap
      between the excited sensitizer and the semiconductor acceptor states. For
      example, the quantum yields for [Os(bpy)2(dcbq)]/TiO2 were phi(417 nm) = 0.18 +/-
      0.02, phi(532.5 nm) = 0.08 +/- 0.02, and phi(683 nm) = 0.05 +/- 0.01. Electron
      transfer to yield ground-state products occurs by lateral intermolecular charge
      transfer. The driving force for charge recombination was in excess of that stored
      in the photoluminescent excited state. Chronoabsorption measurements indicate
      that ligand-based intermolecular electron transfer was an order of magnitude
      faster than metal-centered intermolecular hole transfer. Charge recombination was
      quantified with the Kohlrausch-Williams-Watts model.

PMID- 16787089
TI  - Investigation of dipolar-mediated water-protein interactions in microcrystalline
      Crh by solid-state NMR spectroscopy.
AB  - Water-protein interactions play a major role in protein folding, structure, and
      function, and solid-state NMR has recently been shown to be a powerful tool for
      the site-resolved observation of these interactions in solid proteins. In this
      article we report investigations on possible water-protein dipolar transfer
      mechanisms in the microcrystalline deuterated protein Crh by a set of solid-state
      NMR techniques. Double-quantum (DQ) filtered and edited heteronuclear correlation
      experiments are used to follow direct dipolar water-protein magnetization
      transfers. Experimental data reveal no evidence for "solid-like" water molecules,
      indicating that residence times of solvent molecules are shorter than required
      for DQ creation, typically a few hundred microseconds. An alternative
      magnetization pathway, intermolecular cross-relaxation via heteronuclear nuclear
      Overhauser effects (NOEs), is probed by saturation transfer experiments. The
      significant additional enhancements observed when irradiating at the water
      frequency can possibly be attributed to direct heteronuclear water-protein NOEs;
      however, a contribution from relayed magnetization transfer via chemical exchange
      or proton-proton dipolar mechanisms cannot be excluded.

PMID- 16787091
TI  - Dendrimers as a scaffold for nitric oxide release.
AB  - The preparation and characterization of nitric oxide (NO)-releasing dendrimer
      conjugates are reported. Generation 3 and 5 polypropylenimine dendrimers (DAB-Am
      16 and DAB-Am-64) were modified at the exterior to impart different amine
      functionalities. The ability to store NO on a dendritic scaffold using N
      diazeniumdiolate NO donors was examined via the reaction of primary amine,
      secondary amine, and amide functionalities with high pressures of NO (5 atm). The
      secondary amine dendrimer conjugates exhibited a high storage capacity for NO (up
      to 5.6 micromol NO/mg), greatly increasing the "payload" of released NO over
      existing macromolecular NO donors. The mechanism of diazeniumdiolate
      decomposition was proton initiated, generating NO spontaneously under
      physiological conditions (pH 7.4, 37 degrees C). The NO release durations (>16 h)
      observed for the secondary amine dendrimers were significantly longer compared to
      small molecule alkyl secondary amine diazeniumdiolates, thus illustrating a
      dendritic effect on NO release kinetics. The multivalent exterior of dendrimers
      allows for the future combination of NO donors and other functionalities on a
      single molecular scaffold, enabling diverse utility as NO storage/delivery
      systems.

PMID- 16787090
TI  - Topology of an outer-membrane enzyme: Measuring oxygen and water contacts in
      solution NMR studies of PagP.
AB  - The topology of the bacterial outer-membrane enzyme, PagP, in
      dodecylphosphocholine micelles was studied by solution NMR using oxygen and water
      contacts as probes of hydrophobicity and topology. The effects of oxygen on amide
      protons were measured at an oxygen partial pressure of 20 atm through the
      paramagnetic contribution to the relaxation rates associated with the decay of
      two-spin order. A significant gradation of paramagnetic rates was observed for
      backbone amides belonging to the transmembrane residues. These rates were
      observed to depend on immersion depth, local hydrophobicity, and steric effects.
      Variations in the paramagnetic relaxation rates due to local hydrophobicity or
      steric effects could be, to some extent, averaged out by considering an
      azimuthally averaged quantity. This averaged paramagnetic rate was found to have
      a distinct maximum exactly in the middle of the transmembrane domain of PagP,
      assuming the immersion depth axis is tilted by 25 degrees with respect to the
      barrel axis. Contact between the protein surface and water was assessed by
      measuring the amide decay rates during water saturation. The comparison of local
      contrast effects from both water and oxygen allows one to distinguish among
      steric effects, local hydrophobicity, and immersion depth. For example, the
      absence of contrast effects from either water or oxygen at the periplasmic end of
      beta-strands B and C was consistent with protection effects arising from the
      association with the N-terminal alpha-helix. A parameter defined by the natural
      logarithm of the ratio of the normalized paramagnetic relaxation rate to the
      normalized amide decay rate under water saturation was found to correlate with
      immersion depth of the corresponding backbone amide nuclei. The results suggest
      that the oxygen/water contrast experiments give direct information regarding
      membrane protein topology and surface hydrophobicities, thereby complementing
      existing NMR structure studies and ESR spin-labeling studies.

PMID- 16787092
TI  - An approach to helical tubular self-aggregation using C2-symmetric self
      complementary hydrogen-bonding cavity molecules.
AB  - In an approach to helical self-aggregation, C2-symmetric cavity compounds based
      on the fusion of the bicyclo[3.3.1]nonane and indole framework and incorporating
      two 2-pyridone hydrogen-bonding motifs, compounds (-)-4 (pyrrole N-butyl) and (-)
      5 (pyrrole N-decyl), have been synthesized. The 2-pyridone AD-DA hydrogen-bonding
      motif failed to operate in the solid state as demonstrated by X-ray diffraction
      analysis of (-)-4. Instead, the hydrogen-bonded (D-A) chains ...O=C-N-H...O=C-N
      H...O=C-N-H..., interconnecting columnar stacks, comprise helices of the right
      handed (P) chirality motif. In solution, the aggregation of (-)-5 was studied by
      NMR, electronic, and CD spectroscopies, and VPO measurements. These
      investigations strongly suggest that (-)-5 associates to oligomers in CHCl3 and
      CH2Cl2 using the 2-pyridone motif, fitting the equal K model, and that pi
      stacking can be ruled out as a mode of aggregation. We conclude that the so
      formed aggregates of (-)-5 have a helical structure, based on the fact that only
      helical tubular structures can result when enantiomerically pure 5 uses its 2
      pyridone AD-DA hydrogen-bonding motifs for aggregation.

PMID- 16787094
TI  - Structures, photoluminescence, and reversible vapoluminescence properties of
      neutral platinum(II) complexes containing extended pi-conjugated cyclometalated
      ligands.
AB  - Reacting K2PtCl4 with the tridentate R-C(wedge)N(wedge)C-H2 ligands 2,6-di-(2'
      naphthyl)-4-R-pyridine (R = H, 1a; Ph, 1b; 4-BrC6H4, 1c; 3,5-F2C6H3, 1d) in
      glacial acetic acid, followed by heating in dimethyl sulfoxide (DMSO), gave
      complexes [(R-C(wedge)N(wedge)C)Pt(DMSO)] (2a-d). In the crystal structures of 2a
      c, the molecules are paired in a head-to-tail orientation with Pt...Pt
      separations >6.3 A, and there are extensive close C-H...pi (d = 2.656-2.891 A),
      pi...pi (d = 3.322-3.399 A), and C-H...O=S (d = 2.265-2.643 A) contacts. [(Ph
      C(wedge)N(wedge)C)Pt(PPh3)] (3) was prepared by reacting 2b with PPh3. Reactions
      of 2a-d with bis(diphenylphosphino)methane (dppm) gave [(R
      C(wedge)N(wedge)C)2Pt2(mu-dppm)] (4a-d). Both head-to-head (syn) and head-to-tail
      (anti) conformations were found for 4a.6CHCl3.C5H12, whereas only one
      conformation was observed for 4b.2CHCl3 (syn), 4c.3CH2Cl2 (syn), and 4d.2CHCl3
      (anti). In the crystal structures of 4a-d, there are close intramolecular Pt...Pt
      contacts of 3.272-3.441 A in the syn conformers, and long intramolecular Pt...Pt
      separations of 5.681-5.714 A in the anti conformers. There are weak C-H...X (d =
      2.497-3.134 A) and X...X (X = Cl or Br; d = 2.973-3.655 A) interactions between
      molecules 4a-d and occluded CHCl3/CH2Cl2 molecules, and their solvent channels
      are of varying diameters (approximately 9-28 A). Complexes 2a-d, 3, and 4a-d are
      photoluminescent in the solid state, with emission maxima at 602-643 nm. Upon
      exposure to volatile organic compounds, 4a shows a fast and reversible
      vapoluminescent response, which is most intense with volatile halogenated
      solvents (except CCl4). Powder X-ray diffraction analysis of desolvated 4a
      revealed a more condensed molecular packing of syn and anti complexes than
      crystal 4a.6CHCl3.C5H12.

PMID- 16787093
TI  - X-ray absorption edge spectroscopy and computational studies on LCuO2 species:
      Superoxide-Cu(II) versus peroxide-Cu(III) bonding.
AB  - The geometric and electronic structures of two mononuclear CuO2 complexes,
      [Cu(O2){HB(3-Ad-5-(i)Prpz)3}] (1) and [Cu(O2)(beta-diketiminate)] (2), have been
      evaluated using Cu K- and L-edge X-ray absorption spectroscopy (XAS) studies in
      combination with valence bond configuration interaction (VBCI) simulations and
      spin-unrestricted broken symmetry density functional theory (DFT) calculations.
      Cu K- and L-edge XAS data indicate the Cu(II) and Cu(III) nature of 1 and 2,
      respectively. The total integrated intensity under the L-edges shows that the 's
      in 1 and 2 contain 20% and 28% Cu character, respectively, indicative of very
      covalent ground states in both complexes, although more so in 1. Two-state VBCI
      simulations also indicate that the ground state in 2 has more Cu (/3d8)
      character. DFT calculations show that the in both complexes is dominated by O2(n
      ) character, although the O2(n-) character is higher in 1. It is shown that the
      ligand L plays an important role in modulating Cu-O2 bonding in these LCuO2
      systems and tunes the ground states of 1 and 2 to have dominant Cu(II)-superoxide
      like and Cu(III)-peroxide-like character, respectively. The contributions of
      ligand field (LF) and the charge on the absorbing atom in the molecule (Q(mol)M)
      to L- and K-edge energy shifts are evaluated using DFT and time-dependent DFT
      calculations. It is found that LF makes a dominant contribution to the edge
      energy shift, while the effect of Q(mol)M is minor. The charge on the Cu in the
      Cu(III) complex is found to be similar to that in Cu(II) complexes, which
      indicates a much stronger interaction with the ligand, leading to extensive
      charge transfer.

PMID- 16787095
TI  - Structural basis of the inhibition of Golgi alpha-mannosidase II by mannostatin A
      and the role of the thiomethyl moiety in ligand-protein interactions.
AB  - The X-ray crystal structures of mannose trimming enzyme drosophila Golgi alpha
      mannosidase II (dGMII) complexed with the inhibitors mannostatin A (1) and an N
      benzyl analogue (2) have been determined. Molecular dynamics simulations and NMR
      studies have shown that the five-membered ring of mannostatin A is rather
      flexible occupying pseudorotational itineraries between 2T3 and 5E, and 2T3 and
      4E. In the bound state, mannostatin A adopts a 2T1 twist envelope conformation,
      which is not significantly populated in solution. Possible conformations of the
      mannosyl oxacarbenium ion and an enzyme-linked intermediate have been compared to
      the conformation of mannostatin A in the cocrystal structure with dGMII. It has
      been found that mannostatin A best mimics the covalent linked mannosyl
      intermediate, which adopts a 1S5 skew boat conformation. The thiomethyl group,
      which is critical for high affinity, superimposes with the C-6 hydroxyl of the
      covalent linked intermediate. This functionality is able to make a number of
      additional polar and nonpolar interactions increasing the affinity for dGMII.
      Furthermore, the X-ray structures show that the environment surrounding the
      thiomethyl group of 1 is remarkably similar to the arrangements around the
      methionine residues in the protein. Collectively, our studies contradict the long
      held view that potent inhibitors of glycosidases must mimic an oxacarbenium ion
      like transition state.

PMID- 16787096
TI  - Artificial transfer hydrogenases based on the biotin-(strept)avidin technology:
      fine tuning the selectivity by saturation mutagenesis of the host protein.
AB  - Incorporation of biotinylated racemic three-legged d6-piano stool complexes in
      streptavidin yields enantioselective transfer hydrogenation artificial
      metalloenzymes for the reduction of ketones. Having identified the most promising
      organometallic catalyst precursors in the presence of wild-type streptavidin,
      fine-tuning of the selectivity is achieved by saturation mutagenesis at position
      S112. This choice for the genetic optimization site is suggested by docking
      studies which reveal that this position lies closest to the biotinylated metal
      upon incorporation into streptavidin. For aromatic ketones, the reaction proceeds
      smoothly to afford the corresponding enantioenriched alcohols in up to 97% ee (R)
      or 70% (S). On the basis of these results, we suggest that the enantioselection
      is mostly dictated by CH/pi interactions between the substrate and the eta6-bound
      arene. However, these enantiodiscriminating interactions can be outweighed in the
      presence of cationic residues at position S112 to afford the opposite enantiomers
      of the product.

PMID- 16787097
TI  - Carbonic anhydrase inhibitors: X-ray and molecular modeling study for the
      interaction of a fluorescent antitumor sulfonamide with isozyme II and IX.
AB  - The X-ray crystal structure of the fluorescent antitumor sulfonamide carbonic
      anhydrase (CA, EC, 4.2.1.1) inhibitor (4-sulfamoylphenylethyl)thioureido
      fluorescein (1) in complex with the cytosolic isoform hCA II is reported,
      together with a modeling study of the adduct of 1 with the tumor-associated
      isoform hCA IX. Its binding to hCA II is similar to that of other
      benzesulfonamides, with the ionized sulfonamide coordinated to the Zn2+ ion
      within the enzyme active site, and also participating in a network of hydrogen
      bonds with residues Thr199 and Glu106. The scaffold of 1 did not establish polar
      interactions within the enzyme active site but made hydrophobic contacts (<4.5 A)
      with Gln92, Val121, Phe131, Val135, Leu198, Thr199, Thr200, and Pro202. The
      substituted 3-carboxy-amino-phenyl functionality was at van der Waals distance
      from Phe131, Gly132, and Val135. The bulky tricyclic fluorescein moiety was
      located at the rim of the active site, on the protein surface, and strongly
      interacted with the alpha-helix formed by residues Asp130-Val135. All these
      interactions were preserved in the hCA IX-1 adduct, but the carbonyl moiety of
      the fluorescein tail of 1 participates in a strong hydrogen bond with the
      guanidine moiety of Arg130, an amino acid characteristic of the hCA IX active
      site. This may account for the roughly 2 times higher affinity of 1 for hCA IX
      over hCA II and may explain why in vivo the compound specifically accumulates
      only in hypoxic tumors overexpressing CA IX and not in the normal tissues. The
      compound is in clinical studies as an imaging tool for acute hypoxic tumors.

PMID- 16787098
TI  - Synthesis of bicyclic p-diiodobenzenes via silver-catalyzed Csp-H iodination and
      ruthenium-catalyzed cycloaddition.
AB  - Highly substituted iodobenzenes were efficiently and regioselectively synthesized
      from readily available 1,6-diynes via two-step process consisting of silver
      catalyzed Csp-H iodination and subsequent ruthenium-catalyzed [2 + 2 + 2]
      cycloaddition of resultant iododiynes. Some of the obtained iodobenzenes were
      subjected to palladium-catalyzed C-C bond-forming reactions such as Mizoroki-Heck
      reaction, Sonogashira reaction, and Suzuki-Miyaura coupling, giving highly
      conjugated molecules.

PMID- 16787099
TI  - Divergent growth of coordination dendrimers on surfaces.
AB  - Divergent growth of surface-initiated dendritic nanostructures on gold surfaces
      in a highly controlled, stepwise manner is demonstrated, using metal-organic
      coordination as the binding motif. The repeat unit for dendrimer growth was a
      branched, C3-symmetrical ligand building block bearing three bis-hydroxamate
      groups. The surface initiation sites for dendrimer growth were obtained by the
      formation of a mixed monolayer comprising isolated bis-hydroxamate disulfide
      anchor ligands and octanethiol (OT) at very low anchor/OT ratios. Following
      functionalization of the surface with spaced anchors, alternate immersion in
      solutions of Zr4+ ions and the branched ligand afforded surface-confined
      dendrimers of increasing generation, where the number of generations is
      conveniently controlled by the number of coordination binding sequences. The
      heights of different generation dendrimers are in excellent agreement with values
      predicted by molecular models, as well as with thicknesses of branched
      multilayers prepared by the same procedure on full anchor monolayers. At higher
      generation numbers, gradual dendrimer overlap and coalescence are observed,
      eventually resulting in a continuous overlayer and a transition from 3D to 1D
      growth. A mechanism for the development of dendritic coordination nanostructures
      on surfaces is discussed.

PMID- 16787100
TI  - Validation of the M-C/H-C bond enthalpy relationship through application of
      density functional theory.
AB  - Density functional theory has been used to calculate H-C and M-C bond
      dissociation enthalpies in order to evaluate the feasibility of correlating
      relative M-C bond enthalpies Delta H(M-C)rel with H-C bond enthalpies Delta H(H
      C) via computational methods. This approach has been tested against two
      experimental correlations: a study of (a) Rh(H)(R)(Tp')(CNCH2CMe3) [R =
      hydrocarbyl, Tp' = HB(3,5-dimethylpyrazolyl)3] (Wick, D. D.; Jones, W. D.
      Organometallics 1999, 18, 495) and (b) Ti(R)(silox)2(NHSit-Bu3) (silox = OSit
      Bu3) (Bennett, J. L.; Wolczanski, P. T. J. Am. Chem. Soc. 1997, 119, 10696). We
      show that the observation that M-C bond enthalpies increase more rapidly with
      different substituents than H-C bond enthalpies is reproduced by theory.
      Quantitative slopes of the correlation lines are reproduced within 4% of the
      experimental values with a B3PW91 functional and with very similar correlation
      coefficients. Absolute bond enthalpies are reproduced within 6% for H-C bonds,
      and relative bond enthalpies for M-C bonds are reproduced within 30 kJ mol(-1)
      for Rh-C bonds and within 19 kJ mol(-1) for Ti-C bonds. Values are also
      calculated with the BP86 functional.

PMID- 16787102
TI  - C-C bond formation via C-H bond activation: catalytic arylation and alkenylation
      of alkane segments [J. Am. Chem. Soc. 2002, 124, 13372-13373].

PMID- 16787101
TI  - X-ray illumination induced Fe(II) spin crossover in the Prussian blue analogue
      cesium iron hexacyanochromate.
AB  - The effect of X-ray illumination on the structural properties of the mixed
      valence Prussian blue analogue CsFe(II)[Cr(III)(CN)6] has been studied by time
      dependent high-resolution synchrotron X-ray diffraction. Abrupt isosymmetric
      phase transitions, accompanied by dramatic volume collapse, were found in the
      temperature range 245-265 K, induced by sudden Fe(II) spin transitions from the
      high spin (HS) (4t(2g)2e(g), S = 2) to the low spin (LS) (6t(2g)0e(g), S = 0)
      configuration. Absorption of X-ray photons generates photoexcited Fe(II)(LS)
      domains whose size rapidly grows with time until the percolation threshold is
      reached and the structure collapse is triggered. The persistent character of the
      optically excited spin crossover states derives from the strong electron-phonon
      coupling, associated with the large lattice relaxations, which accompany the
      internal spin rearrangements. It is thus possible to use X-ray light in a
      controllable and efficient way to induce photoswitching between the ground and
      hidden or inaccessible excited states in suitably selected multistable materials
      in the bulk.

PMID- 16787103
TI  - Selective C-arylation of free (NH)-heteroarenes via catalytic C-H bond
      functionalization [J. Am. Chem. Soc. 2003, 125, 5274-5275].

PMID- 16787104
TI  - Diversity synthesis via C-H bond functionalization: concept-guided development of
      new C-arylation methods for imidazoles [J. Am. Chem. Soc. 2003, 125, 10580
      10585].

PMID- 16787105
TI  - Dynamics of the central bottleneck: dual-task and task uncertainty.
AB  - Why is the human brain fundamentally limited when attempting to execute two tasks
      at the same time or in close succession? Two classical paradigms, psychological
      refractory period (PRP) and task switching, have independently approached this
      issue, making significant advances in our understanding of the architecture of
      cognition. Yet, there is an apparent contradiction between the conclusions
      derived from these two paradigms. The PRP paradigm, on the one hand, suggests
      that the simultaneous execution of two tasks is limited solely by a passive
      structural bottleneck in which the tasks are executed on a first-come, first
      served basis. The task-switching paradigm, on the other hand, argues that
      switching back and forth between task configurations must be actively controlled
      by a central executive system (the system controlling voluntary, planned, and
      flexible action). Here we have explicitly designed an experiment mixing the
      essential ingredients of both paradigms: task uncertainty and task simultaneity.
      In addition to a central bottleneck, we obtain evidence for active processes of
      task setting (planning of the appropriate sequence of actions) and task
      disengaging (suppression of the plan set for the first task in order to proceed
      with the next one). Our results clarify the chronometric relations between these
      central components of dual-task processing, and in particular whether they
      operate serially or in parallel. On this basis, we propose a hierarchical model
      of cognitive architecture that provides a synthesis of task-switching and PRP
      paradigms.

PMID- 16787108
TI  - Which drugs for which patients?

PMID- 16787109
TI  - Targeting von Hippel-Lindau syndrome: the future is now.

PMID- 16787110
TI  - Breast CT: a critical perspective.

PMID- 16787107
TI  - Strigolactones stimulate arbuscular mycorrhizal fungi by activating mitochondria.
AB  - The association of arbuscular mycorrhizal (AM) fungi with plant roots is the
      oldest and ecologically most important symbiotic relationship between higher
      plants and microorganisms, yet the mechanism by which these fungi detect the
      presence of a plant host is poorly understood. Previous studies have shown that
      roots secrete a branching factor (BF) that strongly stimulates branching of
      hyphae during germination of the spores of AM fungi. In the BF of Lotus, a
      strigolactone was found to be the active molecule. Strigolactones are known as
      germination stimulants of the parasitic plants Striga and Orobanche. In this
      paper, we show that the BF of a monocotyledonous plant, Sorghum, also contains a
      strigolactone. Strigolactones strongly and rapidly stimulated cell proliferation
      of the AM fungus Gigaspora rosea at concentrations as low as 10(-13) M. This
      effect was not found with other sesquiterperne lactones known as germination
      stimulants of parasitic weeds. Within 1 h of treatment, the density of
      mitochondria in the fungal cells increased, and their shape and movement changed
      dramatically. Strigolactones stimulated spore germination of two other
      phylogenetically distant AM fungi, Glomus intraradices and Gl. claroideum. This
      was also associated with a rapid increase of mitochondrial density and
      respiration as shown with Gl. intraradices. We conclude that strigolactones are
      important rhizospheric plant signals involved in stimulating both the pre
      symbiotic growth of AM fungi and the germination of parasitic plants.

PMID- 16787106
TI  - Formation of the ascidian epidermal sensory neurons: insights into the origin of
      the chordate peripheral nervous system.
AB  - The vertebrate peripheral nervous system (PNS) originates from neural crest and
      placodes. While its developmental origin is the object of intense studies, little
      is known concerning its evolutionary history. To address this question, we
      analyzed the formation of the larval tail PNS in the ascidian Ciona intestinalis.
      The tail PNS of Ciona is made of sensory neurons located within the epidermis
      midlines and extending processes in the overlying tunic median fin. We show that
      each midline corresponds to a single longitudinal row of epidermal cells and
      neurons sharing common progenitors. This simple organization is observed
      throughout the tail epidermis, which is made of only eight single-cell rows, each
      expressing a specific genetic program. We next demonstrate that the epidermal
      neurons are specified in two consecutive steps. During cleavage and gastrula
      stages, the dorsal and ventral midlines are independently induced by FGF9/16/20
      and the BMP ligand ADMP, respectively. Subsequently, Delta/Notch-mediated lateral
      inhibition controls the number of neurons formed within these neurogenic regions.
      These results provide a comprehensive overview of PNS formation in ascidian and
      uncover surprising similarities between the fate maps and embryological
      mechanisms underlying formation of ascidian neurogenic epidermis midlines and the
      vertebrate median fin.

PMID- 16787112
TI  - Liposomal muramyl tripeptide phosphatidyl ethanolamine: ifosfamide-containing
      chemotherapy in osteosarcoma.
AB  - Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) is a synthetic
      biological investigational agent used for treating osteosarcoma. It has been used
      in both canine and human osteosarcoma to reduce pulmonary metastases, the most
      common pattern of treatment failure for sarcomas. L-MTP-PE has been well
      tolerated using the concept of biological cancer therapy during chemotherapy. The
      use of L-MTP-PE with ifosfamide is the best studied combination with single agent
      chemotherapy. This may represent a new treatment choice for osteosarcoma patients
      receiving ifosfamide. Such patients include those with a poor initial
      histological response to primary therapy and/or metastatic disease including
      pulmonary metastases. Reduction of side effects of L-MTP-PE, such as fever and/or
      flu-like symptoms, with ibuprofen has not reduced efficacy. Since improved
      symptom control is possible using drug combinations that are especially effective
      for delayed nausea, outpatient high-dose ifosfamide chemotherapy combined with L
      MTP-PE may lead to a safe and effective therapy while maintaining the patients'
      quality of life.

PMID- 16787113
TI  - Sleeping Beauty transposon system--future trend in T-cell-based gene therapies?
AB  - The Sleeping Beauty (SB) transposon system can mediate stable gene transfer and
      expression in primary human T cells. Optimal in vitro conditions for maximum gene
      transfer efficiencies have been developed with regard to further application of
      the SB transposon system in T cell based gene therapies. This raises the question
      of whether or not the SB transposon system is a convincing alternative for virus
      mediated gene transfer based on the currently available data. Here, we will
      discuss controversial safety and efficacy issues in transposon and viral gene
      transfer technology.

PMID- 16787114
TI  - Breast CT: potential for breast cancer screening and diagnosis.
AB  - Although screening mammography has been shown to be effective in reducing breast
      cancer mortality, a new technique called breast computed tomography (CT) is being
      studied in the hope that breast cancer can be detected even earlier. A prototype
      unit has been designed, fabricated and tested at the University of California,
      Davis, USA, and is currently being used in a Phase II clinical trial to study the
      feasibility of breast CT for breast cancer detection and diagnosis. A total of 46
      volunteers and patients have been imaged, and the breast CT images show
      impressive anatomical detail of the breast that is not appreciated in
      mammography. The radiation dose levels needed to produce excellent image quality
      are equal to two-view mammography. Further study of breast CT is needed to better
      understand its potential role in breast cancer screening and diagnosis.

PMID- 16787115
TI  - Genomics in breast and prostate cancer: assessment of the current state and
      future perspectives.
AB  - Genomic approaches to cancer are beginning to have an important impact in
      unraveling the complex etiologies of this disease, as well as allowing us to
      rationally treat afflicted patients. In this article, we will focus largely on
      genomic approaches to breast and prostate cancer susceptibility, as well as
      pharmacogenomic approaches to treatment. Current genomic approaches to cancer
      susceptibility have led to some significant, if not spectacular, successes which
      include breast cancer. More modest achievements, if not outright failures, such
      as in prostate cancer, are also notable and will be discussed further. We propose
      interdisciplinary approaches involving basic, clinical and population scientists
      to vigorously attack the cancer problem scientifically and with more
      organization. We highlight recent successes and suggest new approaches with a
      personal, if not provocative, perspective.

PMID- 16787116
TI  - Genetics of hereditary diffuse gastric cancer: progress and future challenges.
AB  - Hereditary diffuse gastric cancer (HDGC) is a rare cancer susceptibility
      syndrome. One third of HDGC syndrome families carry germline mutations of the E
      cadherin gene. Owing to the limitation of the current endoscopic screening
      techniques and since no chemoprevention is yet available, total prophylactic
      gastrectomy is the only option offered to carriers of inactivating mutations in
      genetic counseling. In this regard, 30% of the E-cadherin germline mutations
      reported to date are of the missense type, and since their pathogenic
      significance is not straightforward, the management of carriers of such mutations
      is suboptimal. In the absence of definitive clinical evidence, functional in
      vitro studies together with in silico analysis have been used to infer the
      pathogenic significance of germline missense mutations. Since most of the HDGC
      families reported to date are negative for E-cadherin germline mutations, the
      identification of alternative genes underlying the tumorigenesis of diffuse
      gastric has become an important target for research.

PMID- 16787117
TI  - Role of the microenvironment in multiple myeloma bone disease.
AB  - Multiple myeloma bone disease occurs in over 70-80% of patients with myeloma and
      represents a significant source of morbidity and mortality. Early in multiple
      myeloma bone disease there is a balance between osteoclast activation and
      osteoblast suppression. However, this balance appears to be lost in advanced
      disease, resulting in the development of lytic lesions and bone destruction.
      Osteoclast activation occurs through a variety of factors, including receptor
      activator of nuclear factor-kappaB ligand, macrophage inflammatory protein
      1alpha, interleukin-3 and interleukin-6, resulting in osteoclast stimulation and
      bone resorption. There is also significant osteoblast suppression through the
      inhibitory actions of interleukin-3, dickkopf 1, secreted frizzled-related
      protein-2 and interleukin-7. Understanding the mechanisms behind myeloma bone
      disease will help to identify potential future therapeutic interventions to help
      ameliorate or prevent osteoblast suppression and decrease osteoclast activation,
      with the goal of improving the overall quality of life for patients with multiple
      myeloma.

PMID- 16787118
TI  - Strong-arming immune regulation: suppressing regulatory T-cell function to treat
      cancers.
AB  - In recent years there has been an accelerated understanding of immune regulatory
      mechanisms. Much of this immune regulation is linked to a collection of
      specialized regulatory cells of the T-cell lineage (Tregs). This collection
      consists of Tregs that are either thymically derived or peripherally induced.
      Tregs are important for controlling potentially autoreactive immune effectors and
      immune responses to foreign organisms and molecules. Their importance in
      maintaining immune homeostasis and the overall health of an organism cannot be
      overstated. However, there is a dark side, and Tregs may also be involved in the
      pathogenesis of malignancies. Evidence shows that tumors induce or recruit Tregs
      to block antitumor effectors. Thus, there are efforts underway to identify
      approaches that specifically inhibit the function of intratumoral Tregs, which
      could lead to increased immunity to tumors without off-target immune-related
      pathologies (i.e., autoimmune disease). In this review, the biology of Tregs is
      discussed along with their involvement in malignancies and emerging strategies to
      block their function.

PMID- 16787120
TI  - Can molecular profiling of cytogenetic subgroups draw a roadmap for
      individualizing therapy in myelodysplastic syndromes?
AB  - Therapeutic options for the heterogeneous hematopoietic disorders grouped under
      the myelodysplastic syndromes (MDS) have been difficult to develop, even though
      the incidence of this disease is increasing because of the ageing population.
      Several drugs have now been shown to have therapeutic efficacy in subgroups of
      patients, but the main challenge is still the preselection of the patient for a
      given strategy. To state the problem simply, effective therapies may already
      exist for a substantial number of MDS patients, but we do not know how to match
      the right drug to the right patient. Cytogenetic abnormalities have provided some
      treatment guidance, however these are generally restricted to patients known to
      have a better prognosis. To develop reliable predictive assays in patients with
      complex or more advanced diseases, we will have to delve deeper than
      cytogenetics. This review summarizes what is known about the clinical and
      biological characteristics of various karyotypic subgroups of MDS, and proposes a
      roadmap for combining the bedside-to-bench approach with the use of DNA
      microarray analysis in developing expression profiles that can serve as a guide
      in the preselection of treatment options for individual MDS patients.

PMID- 16787119
TI  - Specific targeting of gene therapy to prostate cancer using a two-step
      transcriptional amplification system.
AB  - Significant advances in gene therapy have been made as a result of the
      improvement of gene delivery systems, discovery of new therapeutic genes, better
      understanding of mechanisms of disease progression, exploration and improvement
      of tissue-specific gene regulatory sequences, and development of better
      prodrug/enzyme systems. This review discusses adenoviral-based and prostate
      specific cancer gene therapy--emphasizing tissue-specific promoter choices to
      increase gene therapy safety and specificity--and the development of prostate
      targeted vectors, with a focus on the two-step transactivation system for
      amplifying gene expression, specifically in prostate cancer cells. Several
      examples will be discussed for the scientific basis and therapeutic applications.
      In addition, prostate cancer gene therapy clinical trials and future directions
      in this field will also be described briefly.

PMID- 16787121
TI  - Modulation of response to tumor therapies by the extracellular matrix.
AB  - The composition of the extracellular matrix in tumors is vastly different from
      that found in the normal tissue counterparts. As the extracellular matrix can
      signal to cells via integrin binding and activation, which is known to modulate
      cell proliferation, survival and migration, it may influence the response of both
      tumor and endothelial cells to anticancer therapies. Certain tumor-associated
      extracellular matrix proteins have been shown to confer resistance to
      chemotherapeutic drugs, radiation and anti-angiogenic factors. The current
      literature regarding this phenomenon and the potential therapeutic modalities to
      overcome extracellular matrix-induced resistance will be discussed.

PMID- 16787126
TI  - Patients with diabetes and depression may need additional support for exercise.
AB  - OBJECTIVE: To examine the association between depressive symptoms and exercise
      related variables among patients with type 2 diabetes. METHODS: Surveys were
      completed by 207 primary care patients diagnosed with type 2 diabetes (52%
      female; 95% white; mean age = 63 years). Multiple linear regression analyses were
      conducted. RESULTS: Lower use of relapse prevention behavior was significantly
      associated with higher depression scores in a multivariate model. CONCLUSIONS:
      Patients with diabetes and depression have barriers to exercise (eg, fewer skills
      for relapse prevention) and may require additional support for exercise
      initiation and maintenance.

PMID- 16787125
TI  - Comparison of 3 interventions to increase walking in sedentary women.
AB  - OBJECTIVE: To increase walking activity in sedentary women. METHODS: Women (N =
      253) were randomly assigned to 1 of 3 groups: video education/control, brief
      telephone calls with no counseling, and telephone calls with counseling.
      Assessments were made at baseline, 6 months, and 1 year. RESULTS: All
      interventions increased the number of reported minutes walked and decreased the
      time to walk a mile. CONCLUSIONS: The variability in the telephone counseling and
      brief telephone call groups seemed to suggest a group of participants who were
      high responders.

PMID- 16787127
TI  - Tobacco cessation and weight loss: trends in media coverage.
AB  - OBJECTIVE: To examine time trends in amount of media coverage on tobacco
      cessation versus weight loss and test whether the 2 topics compete for limited
      media attention. METHODS: Monthly print and broadcast media coverage from 1995 to
      2003 was estimated. RESULTS: Tobacco and weight coverage were uncorrelated.
      Tobacco coverage peaked in 1997-98, whereas coverage of weight increased linearly
      between 1995 and 2003. CONCLUSION: Tobacco and weight topics do not appear to
      compete for media coverage. Interest in weight topics is rising, consistent with
      its growing public health importance. Coverage of tobacco is declining,
      suggesting a need to keep tobacco and cessation in the public eye.

PMID- 16787128
TI  - Disparity of physicians' utilization of tobacco treatment services.
AB  - OBJECTIVES: To evaluate the familiarity with and utilization of tobacco treatment
      resources among physicians. METHODS: The NJ State Physician Census was mailed to
      30,639 physicians with 8150 responding (26.6%). Data from 4598 direct patient
      care physicians were analyzed. RESULTS: Pulmonologists, cardiologists, and family
      physicians had the highest levels of familiarity and referral, whereas
      psychiatrists, neurologists, ophthalmologists, and surgeons had the lowest.
      Physicians who were younger, female, who had more teaching hours, and who
      accepted fewer new patients all had higher familiarity. CONCLUSIONS: Familiarity
      with tobacco dependence treatment resources varies by physician characteristics.
      Increasing physicians' utilization of these resources is an important research
      priority.

PMID- 16787129
TI  - Health behavior goals of cardiac patients after hospitalization.
AB  - OBJECTIVES: To examine the types and influences of health behavior goals self
      selected by post hospitalized cardiac patients. METHODS: Subjects participated in
      a trial assessing the effectiveness of a health behavior change program. RESULTS:
      Nearly 95% of smokers and 89.7% of patients with elevated weights selected a
      smoking and/or dietary modification goal, respectively. Only 43.8% of physical
      activity goal patients started a rehabilitation program. Although no consistent
      relationships were found between patient characteristics and type of goal(s)
      selected, significant improvements in readiness to change levels occurred.
      CONCLUSIONS: Many patients can make health behavior progress consistent with
      behaviors needing improvements by clinical criteria.

PMID- 16787130
TI  - Factors associated with quitting smoking at a tobacco dependence treatment
      clinic.
AB  - OBJECTIVE: To identify factors associated with successful quitting at a free
      tobacco treatment clinic. METHODS: A cohort study of the first 1021 patients who
      made a quit attempt. Baseline and treatment variables were recorded, and logistic
      regression was used to identify factors associated with abstinence at 4-week and
      6-month follow-up. RESULTS: Three hundred twenty (31.3%) patients reported
      tobacco abstinence at 6 months. Several markers of low socioeconomic status and
      high nicotine dependence were predictive of poorer smoking cessation outcomes.
      Compliance with evidence-based treatment was associated with improved treatment
      outcome, as was older age and having more than 2 children. CONCLUSIONS: Efforts
      should be made to enhance treatment compliance among smokers with indicators of
      high nicotine dependence and low socioeconomic status.

PMID- 16787131
TI  - Factors predicting pregnancy smoking in Southern Appalachia.
AB  - OBJECTIVE: To examine sociodemographic, medical, and substance use factors
      associated with smoking continuation during pregnancy. METHODS: Data from 221
      consecutive prenatal patients were analyzed. RESULTS: Of the 67% who were pre
      pregnancy smokers (n=148), 27% quit during pregnancy, whereas another 43% reduced
      by > 1/4 pack/day. Women who continued to smoke had lower incomes, more prior
      pregnancies, were less likely to have adequate prenatal care, and smoked more and
      for more years than did women who quit during pregnancy. CONCLUSION: Several
      characteristics predicted pregnancy smoking in this sample. Results suggest ways
      to more effectively target pregnant women for successful smoking cessation.

PMID- 16787132
TI  - Physical activity and quality of life improvements before obesity surgery.
AB  - OBJECTIVE: To examine quality of life (QOL), physical activity (PA), and physical
      activity readiness (PAR) among gastric-bypass surgery (GBS) candidates. METHODS:
      The SF-36v2, International Physical Activity Questionnaire, and a stages-of
      change measure assessed QOL, PA, and PAR respectively across 2 presurgical
      visits. RESULTS: Increases in mental QOL, PA, and PAR were observed across
      visits. Sufficiently physically active participants reported significantly higher
      physical QOL than did insufficiently physically active participants. CONCLUSIONS:
      Findings demonstrating positive presurgical changes in PA and PA readiness as
      well as the association between PA and QOL warrant increased efforts to promote
      PA adoption and maintenance among GBS candidates.

PMID- 16787133
TI  - Adolescents' smoking behaviors, beliefs on the risks of smoking, and exposure to
      ETS in Juarez, Mexico.
AB  - OBJECTIVE: To assess the smoking behaviors, beliefs about the risks of smoking,
      and exposure to ETS among adolescents in Juarez, Mexico. METHODS: A cross
      sectional study was conducted with sixth-grade students (N=506), aged 11-13 years
      old, attending 6 randomly selected schools. Schools were classified by school
      setting and SES. RESULTS: Students attending a low SES school setting were more
      likely to have smoked (P < 0.01), be current smokers (P < 0.01), be exposed to
      ETS at home and in public (P < 0.01) than were students attending a middle or
      high SES school. CONCLUSION: Smoking interventions should target students
      attending school in low SES settings.

PMID- 16787139
TI  - Diabetes therapy trials with inhaled insulin.
AB  - Administration of insulin by inhalation was first attempted > 50 years ago. At
      that time, little was known concerning effective delivery systems and insulin
      formulations. The recent development of pulmonary delivery systems for the
      administration of insulin is driven by the reluctance of patients and their
      providers to initiate insulin earlier in the course of Type 2 diabetes, the
      desire to reduce the number of daily insulin injections for both Type 1 and 2
      patients, and the recent emphasis on intensified glycaemic control including
      postprandial glycaemic control. The deep lung is a unique mucosal tissue having a
      surface area of > 100 m2 and is readily accessible both to the external
      environment and to drug delivery, provided that appropriate conditions are met.
      There have been four mid- to late-phase pulmonary insulin programmes using modern
      inhalation devices that will be reported in this paper. The programmes differ in
      the choice of delivery systems, the formulations of insulin and reported
      bioavailability, pharmacokinetic and glucodynamic profiles and adverse events.
      However, all systems successfully deliver insulin to the deep lung and biological
      effectiveness compares favourably with injected subcutaneous insulins.

PMID- 16787138
TI  - Inhibitors of cyclic nucleotide phosphodiesterase 3 and 5 as therapeutic agents
      in heart failure.
AB  - Cyclic nucleotide phosphodiesterases (PDE) 3 and 5 regulate cAMP and cGMP
      signalling in cardiac and smooth muscle myocytes. Important advances in the
      understanding of the roles of these enzymes have recently been made. PDE3
      inhibitors have inotropic and vasodilatory properties, and although they acutely
      improve haemodynamics in patients with heart failure, they do not improve long
      term morbidity and mortality. Although combination therapy with beta-adrenergic
      receptor antagonists or selective inhibition of specific PDE3 isoforms might
      result in a more favourable long-term outcome, more clinical data are needed to
      test this proposition. The role of PDE5 inhibitors in the treatment of cardiac
      disease is evolving. PDE5 inhibitors cause pulmonary and systemic vasodilation.
      How these drugs will compare with other vasodilators in terms of long-term
      outcomes in patients with heart failure is unknown. Recent studies also suggest
      that PDE5 inhibitors may have antihypertropic effects, exerted through increased
      myocardial cGMP signalling, that could be of additional benefit in patients with
      heart failure.

PMID- 16787140
TI  - Investigational PPAR-gamma agonists for the treatment of Type 2 diabetes.
AB  - The tremendous increase in the global prevalence of Type 2 diabetes (T2D) and its
      conglomeration of metabolic disorders has dramatically intensified the search for
      innovative therapies to fight this emerging epidemic. Over the last decade, the
      family of nuclear receptors, especially the peroxisome proliferator-activated
      receptors (PPARs), has emerged as one of the most important drug targets aimed at
      combating the metabolic syndrome. Consequently, compounds that activate the PPARs
      have served as potential therapeutics for the treatment of T2D and the metabolic
      anomalies associated with this disorder. This review focuses on the currently
      marketed compounds and also describes the discovery and development of the next
      generation of PPAR ligands that are under investigation for the potential
      treatment of T2D and the metabolic syndrome.

PMID- 16787141
TI  - Promising new treatments for neovascular age-related macular degeneration.
AB  - Angiogenesis, the growth of new blood vessels from existing blood vessels, is
      responsible for vision loss in a variety of ophthalmic diseases. In neovascular
      age-related macular degeneration (AMD), the leading cause for legal blindness in
      many industrialised countries, abnormal blood vessels grow in the macula and
      cause blindness. There are a number of factors important in the angiogenic
      cascade but VEGF-A has been implicated in recent years as the major factor
      responsible for neovascular and exudative diseases of the eye. Numerous
      antiangiogenic drugs are in development but anti-VEGF drugs have shown great
      promise in treating neovascular AMD and other ocular diseases, and many of these
      drugs have been adopted from oncology where antiangiogenic therapy is gaining
      wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have
      brought the hope of vision improvement to a significant proportion of patients.
      This review provides an overview on angiogenic mechanisms, potential
      antiangiogenic treatment strategies and different antiangiogenic drugs with
      special focus on neovascular AMD.

PMID- 16787142
TI  - Combination therapy using LHRH and somatostatin analogues plus dexamethasone in
      androgen ablation refractory prostate cancer patients with bone involvement: a
      bench to bedside approach.
AB  - The development of resistance to anticancer therapies is a major hurdle in
      preventing long-lasting clinical responses to conventional therapies in hormone
      refractory prostate cancer. Herein, the molecular evidence documenting that bone
      metastasis microenvironment survival factors (mainly the paracrine growth hormone
      independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and
      the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived
      IGF-1 production) produce an epigenetic form of prostate cancer cells that are
      resistant to proapoptotic therapies is reviewed. Consequently, the authors
      present the conceptual framework of a novel antibone microenvironment survival
      factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation
      refractory prostate cancer (a combination of conventional androgen ablation
      therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with
      dexamethasone plus somatostatin analogue, which yielded durable objective
      responses and major improvement of bone pain and performance status in stage D3
      prostate cancer patients.

PMID- 16787143
TI  - Immunomodulatory drugs in myelodysplastic syndromes.
AB  - This review summarises the mechanism of action of immunomodulatory analogues of
      thalidomide and their use in myelodysplastic syndromes. Thalidomide was found to
      have a response rate of approximately 20% in these patients. Lenalidomide--which
      is more potent and less toxic than thalidomide--has been used in three clinical
      trials and produced the best responses (60 - > 90%) in low- and intermediate-1
      risk transfusion-dependent patients with del(5q). The responses are purely
      erythroid in nature, and are associated with major cytogenetic responses in > 50%
      of the del(5q) patients. Non-del(5q) low- and intermediate-1-risk transfusion
      dependent patients also had a approximately 25% incidence of transfusion
      independence following therapy with lenalidomide. Median time to response is
      approximately 4 weeks and 90% of patients respond within 12 weeks. The precise
      mechanism of action remains unknown but anticytokine, antiangiogenic and
      immunomodulatory properties are thought to play a role.

PMID- 16787145
TI  - Pirfenidone for the treatment of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is an under-recognised, rare, progressive
      disease of the lungs with unknown aetiology and high mortality. The currently
      advocated pathogenic mechanism is represented by progressive multifocal fibrosis.
      It is diagnosed based on clinical, radiographic, physiological and
      histopathological criteria. Existing therapeutic guidelines recommend anti
      inflammatory and immunosuppressive combinations, despite proven limited efficacy.
      There is no therapy approved specifically for IPF, but several antifibrotic
      agents are currently under development for this indication. Pirfenidone is an
      antifibrotic agent potentially effective for IPF therapy, and preclinical and
      available clinical data support its use in IPF. Future clinical studies are
      expected to provide more consistent information on survival benefit, lung
      function and health-related quality of life.

PMID- 16787146
TI  - Analysing the output from primary screening.
AB  - From a perspective of process knowledge and enhancement, the analysis of the
      results of biological screening should not be limited to the outcome of specific
      projects, but additionally encompass a process centric view. Summarising outcomes
      across multiple projects is a powerful tool to gain a greater understanding of
      biological screening that will also enable optimisation of the strategy for
      specific projects or target classes. We have analysed a set of 73,651 compounds
      with reproducible (confirmed) results from 63 high-throughput screening (HTS)
      campaigns to reveal the underlying trends in the population of active compounds.
      We have focused on the overall physico-chemical profile of compound populations
      derived from biological screening since the in vivo activity of drug molecules is
      the result of physico-chemical and structural properties of the compound.

PMID- 16787144
TI  - Pegylated arginine deiminase: a novel anticancer enzyme agent.
AB  - Pegylated arginine deiminase (ADI-PEG20) is a novel anticancer enzyme that
      produces depletion of arginine, which is a nonessential amino acid in humans.
      Certain tumours, such as malignant melanoma and hepatocellular carcinoma, are
      auxotrophic for arginine. These tumours that are sensitive to arginine depletion
      do not express argininosuccinate synthetase, a key enzyme in the synthesis of
      arginine from citrulline. ADI-PEG20 inhibits human melanomas and hepatocellular
      carcinomas in vitro and in vivo. Phase I - II trials in patients with melanoma
      and hepatocellular carcinomas have shown the drug to have antitumour activity and
      tolerable side effects. Large Phase II trials and randomised, controlled Phase
      III trials are needed to determine its overall efficacy in the treatment of these
      malignancies and others.

PMID- 16787147
TI  - Automated high content screening for phosphoinositide 3 kinase inhibition using
      an AKT 1 redistribution assay.
AB  - High Content Screening (HCS), a combination of fluorescence microscopic imaging
      and automated image analysis, has become a frequently applied tool to study test
      compound effects in cellular disease-modelling systems. In this work, we
      established a medium to high throughput HCS assay in the 384-well format to
      measure cellular type I phosphoinositide 3 kinase (PI3K) activity. Type I PI3K is
      involved in several intracellular pathways such as cell survival, growth and
      differentiation as well as immunological responses. As a cellular model system we
      used Chinese Hamster Ovary (CHO) cells that had been stably transfected with
      human insulin receptor (hIR) and an AKT1-enhanced green fluorescent protein
      (EGFP) fusion construct. Upon stimulation of the hIR with insulin-like growth
      factor-1 (IGF-1), PI3K was activated to phosphorylate phosphatidylinositol
      (PtdIns)-4,5-bisphosphate at the 3-position, resulting in the recruitment of AKT1
      EGFP to the plasma membrane. The AKT1-EGFP redistribution assay was robust and
      displayed little day-to-day variability, the quantification of the fluorescence
      intensity associated with plasma membrane spots delivered good Z' statistics. A
      novel format of compound dose-response testing was employed using serial
      dilutions of test compounds across consecutive microtiter plates (MTPs). The dose
      response testing of a PI3K inhibitor series provided reproducible IC50 values.
      The profiling of the redistribution assay with isoform-selective inhibitors
      indicates that PI3Kalpha is the main isoform activated in the CHO host cells
      after IGF-1 stimulation. Toxic compound side effects could be determined using
      automated image analysis. We conclude that the AKT1-EGFP redistribution assay
      represents a solid medium/high throughput screening (MTS/HTS) format to determine
      the cellular activity of PI3K inhibitors under conditions of growth factor
      stimulation.

PMID- 16787148
TI  - Successful screening of large encoded combinatorial libraries leading to the
      discovery of novel p38 MAP kinase inhibitors.
AB  - Screening of more than 2 million compounds comprising 41 distinct encoded
      combinatorial libraries revealed a novel structural class of p38 mitogen
      activated protein (MAP) kinase inhibitors. The methodology used for screening
      large encoded combinatorial libraries combined with the statistical
      interpretation of screening results is described. A strong preference for a
      particular triaminotriazine aniline amide was discovered based on biological
      activity observed in the screening campaign. Additional screening of a focused
      follow-up combinatorial library yielded data expanding the unique combinatorial
      SAR and emphasizing an extraordinary preference for this particular building
      block and structural class. The preference is further highlighted when the p38
      inhibitor data set is compared to data obtained for a panel of other kinases.

PMID- 16787149
TI  - A pseudo-ligand approach to virtual screening.
AB  - A virtual screening method is presented that is grounded on a receptor-derived
      pharmacophore model termed "virtual ligand" or "pseudo-ligand". The model
      represents an idealized constellation of potential ligand sites that interact
      with residues of the binding pocket. For rapid virtual screening of compound
      libraries the potential pharmacophore points of the virtual ligand are encoded as
      an alignment-free correlation vector, avoiding spatial alignment of pharmacophore
      features between the pharmacophore query (i.e., the virtual ligand) and the
      candidate molecule. The method was successfully applied to retrieving factor Xa
      inhibitors from a Ugi three-component combinatorial library, and yielded high
      enrichment of actives in a retrospective search for cyclooxygenase-2 (COX-2)
      inhibitors. The approach provides a concept for "de-orphanizing" potential drug
      targets and identifying ligands for hitherto unexplored or allosteric binding
      pockets.

PMID- 16787150
TI  - Microarray technology as a universal tool for high-throughput analysis of
      biological systems.
AB  - Over the last years microarray technology has become one of the principal
      platform technologies for the high-throughput analysis of biological systems.
      Starting with the construction of first DNA microarrays in the 1990s, microarray
      technology has flourished in the last years and many different new formats have
      been developed. Peptide and protein microarrays are now applied for the
      elucidation of interaction partners, modification sites and enzyme substrates.
      Antibody microarrays are envisaged to be of high importance for the high
      throughput determination of protein abundances in translational profiling
      approaches. First cell microarrays have been constructed to transform microarray
      technology from an in vitro technology to an in vivo functional analysis tool.
      All of these approaches share a common prerequisite: the solid support on which
      they are generated. The demands on this solid support are thereby as manifold as
      the applications themselves. This review is aimed to display the recent
      developments in surface chemistry and derivatization, and to summarize the latest
      developments in the different application areas of microarray technology.

PMID- 16787151
TI  - Application of chemical arrays in screening elastase inhibitors.
AB  - Protein chip technology provides a new and useful tool for high-throughput
      screening of drugs because of its high performance and low sample consumption. In
      order to screen elastase inhibitors on a large scale, we designed a composite
      microarray integrating enzyme chip containing chemical arrays on glass slides to
      screen for enzymatic inhibitors. The composite microarray includes an active
      proteinase film, screened chemical arrays distributed on the film, and substrate
      microarrays to demonstrate change of color. The detection principle is that
      elastase hydrolyzes synthetic colorless substrates and turns them into yellow
      products. Because yellow is difficult to detect, bromochlorophenol blue (BPB) was
      added into substrate solutions to facilitate the detection process. After the
      enzyme had catalyzed reactions for 2 h, effects of samples on enzymatic activity
      could be determined by detecting color change of the spots. When chemical samples
      inhibited enzymatic activity, substrates were blue instead of yellow products. If
      the enzyme retained its activity, the yellow color of the products combined with
      blue of BPB to make the spots green. Chromogenic differences demonstrated whether
      chemicals inhibited enzymatic activity or not. In this assay, 11,680 compounds
      were screened, and two valuable chemical hits were identified, which demonstrates
      that this assay is effective, sensitive and applicable for high-throughput
      screening (HTS).

PMID- 16787152
TI  - Microarray and nanotechnology applications of functional nanoparticles.
AB  - Microarrays are a sensitive, specific, miniaturized devices that may be used to
      detect selected DNA sequences and proteins, or mutated genes associated with
      human diseases. Several methods have been developed to detect the binding of
      complementary molecules to microarrays by generating an optical signal. One of
      the most commonly used molecular labeling methods at present is fluorescence, but
      its application is expensive due to sophisticated equipment required to design
      the platform, hybridize it, and interpret the images derived from microarray
      based studies. This is a drawback for its use in laboratories and clinical
      services. Another less expensive procedure having similar sensitivity and
      specificity is DNA and protein functional nanoparticles (FNP). Nanoparticles are
      sphere-like biocompatible materials made of inert silica, metal or crystals of a
      nanometer in size, which are generally coated with a thin gold layer. They may be
      used as hybridization probes in single nucleotide polymorphism (SNP) screening
      and to detect biological markers for cancer, infection, and cardiovascular
      diseases.

PMID- 16787153
TI  - Nitrogen-containing macrocycles as host molecules for the recognition of
      undissociated phenol derivatives: mechanism of potentiometric signal generation.
AB  - The mechanism of the generation of potentiometric signals of corrole- and
      calix[4]pyrrole-containing liquid membrane electrodes was elucidated and compared
      in the presence of the neutral forms of phenol derivatives. In addition, the
      influence of lipophilic, anionic or cationic salts on this phenomenon was
      explored. Finally, the relationship between the acid-base properties of the
      phenolic guests and the hydrogen bond donor activity of the calix[4]pyrrole and
      corrole hosts, and the influence on the molecular recognition phenomenon
      occurring at the organic/aqueous interface are discussed.

PMID- 16787155
TI  - Utility of mass spectrometry for pharmaceutical profiling applications.
AB  - MS has great utility for pharmaceutical profiling, the measurement of
      physicochemical and metabolic properties that are crucial to the discovery and
      development of new drug candidates. An evaluation of the capabilities of MS to
      improve the speed, specificity, sensitivity and cost per compound of method in
      development indicates when MS technologies have utility compared to other
      analytical techniques. MS has been used successfully for methods that profile the
      critical properties: permeability, lipophilicity, plasma and solution stability,
      solubility, plasma protein binding and integrity. In general, MS has utility in
      these methods using analytical strategies involving unique MS technologies (e.g.,
      parallel multiplexed interfaces, trap-and-elute), orthogonal detection to UV,
      high sensitivity for low LOQs, low concentration studies, highly specific MS/MS
      SRM, combinatorial analysis, use of internal standards, providing initial
      structural data in addition to quantitative and facile integration with HPLC
      autosamplers and other hardware that allow enhanced on-line experiments.
      Ultimately, it is important to evaluate the appropriateness of any technique that
      is being considered for use in a method, to insure that it best meets all of the
      criteria for the organization's needs.

PMID- 16787156
TI  - Utility of mass spectrometry for in-vitro ADME assays.
AB  - A balance between pharmacological activity, safety and drug metabolism and
      pharmacokinetics (DMPK) attributes determines the fate of a new chemical entity
      (NCE) in drug discovery. Because of the increased number of NCEs requiring DMPK
      evaluation, several in vitro higher-throughput screens and counter screens
      designed to evaluate DMPK attributes have been introduced in drug discovery. The
      DMPK screens evaluate NCEs for potential absorption, metabolism, drug-drug
      interactions, brain penetration, protein binding and pharmacokinetics. Higher
      throughput analytical methodologies for the determination of either a common end
      product of a screen or the parent compound (and/or possible metabolites) are
      essential for successful DMPK screens. Because of its speed, sensitivity and
      specificity, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become
      the technology of choice for sample analysis. In this review, several in vitro
      screening assays that we employ in drug discovery are discussed with an emphasis
      on LC-MS/MS role in accelerating them.

PMID- 16787157
TI  - Increasing speed and throughput when using HPLC-MS/MS systems for drug metabolism
      and pharmacokinetic screening.
AB  - Both combinatorial chemistry and parallel synthesis provide a valuable means for
      the production of large numbers of compounds with diverse molecular architectures
      that become available for various drug discovery experiments. In both the lead
      optimization and lead selection stages, one requirement that is common for many
      processes is the need for bioanalytical support. This review summarizes current
      high throughput strategies and efficient methodologies that are employed for drug
      metabolism and pharmacokinetic (DMPK) screens for a series of drug discovery
      compounds. For these types of assays, high performance liquid chromatography
      coupled to a tandem mass spectrometer (HPLC-MS/MS) has now become the technique
      of choice. The major high throughput strategies including sample reduction and
      cassette dosing are discussed. The methods for increasing the speed of HPLC-MS/MS
      based analyses, such as fast chromatography, direct sample injection, parallel
      technologies and combined ionization interfaces are also presented in this
      review. In addition, the special challenges when performing HPLC-MS/MS
      bioanalysis, such as the choice of ionization sources, matrix ionization
      suppression and the potential for endogenous interferences, are addressed.

PMID- 16787158
TI  - LC-MS Development strategies for quantitative bioanalysis.
AB  - Although quantitative bioanalysis using liquid chromatography in conjunction with
      atmospheric pressure ionization tandem mass spectrometry (LC-MS/MS) has been in
      use for approximately fifteen years, new concepts and technologies are
      continuously being introduced to enhance the multiple steps of quantitative LC
      MS/MS bioanalysis. In this review article, we have focused on concepts and
      technologies that have recently been introduced to achieve further improvements
      in biological sample collection/storage and extraction, chromatography and mass
      spectrometric detection. Under these major headings, a number of specific topics
      are presented, summarizing the most recent findings in these areas. Included
      among the topics discussed are: off-line plasma extraction, on-line plasma
      extraction, enhanced mass resolution, atmospheric pressure photoionization, high
      field asymmetric waveform ion mobility spectrometry, electron capture atmospheric
      pressure chemical ionization, enhancing MS detection via formation of anionic and
      cationic adducts, chemical derivatization, ultra-performance chromatography,
      hydrophilic interaction chromatography, and MS-friendly ion-pair reversed-phase
      chromatography. In the end, we discuss potential pitfalls in LC-MS/MS bioanalysis
      and the means to avoid them. Such pitfalls may occur due to mass spectral
      interference from metabolites or prodrugs, due to the use of inappropriate
      calibration standard and quality control samples for analysis involving unstable
      drugs or metabolites, and due to the wild card phenomenon commonly known as the
      matrix effect.

PMID- 16787159
TI  - Application of mass spectrometry for metabolite identification.
AB  - Metabolism studies play a pivotal role in drug discovery and development.
      Characterization of metabolic "hot-spots" as well as reactive and
      pharmacologically active metabolites is critical to designing new drug candidates
      with improved metabolic stability, toxicological profile and efficacy. Metabolite
      identification in the preclinical species used for safety evaluation is required
      in order to determine whether human metabolites have been adequately tested
      during non-clinical safety assessment. From an instrumental standpoint, high
      performance liquid chromatography (HPLC) coupled with mass spectrometry (MS)
      dominates all analytical tools used for metabolite identification. The general
      strategies employed for metabolite identification in both drug discovery and drug
      development settings together with sample preparation techniques are reviewed
      herein. These include a discussion of the various ionization methods, mass
      analyzers, and tandem mass spectrometry (MS/MS) techniques that are used for
      structural characterization in a modern drug metabolism laboratory. Mass
      spectrometry-based techniques, such as stable isotope labeling, on-line H/D
      exchange, accurate mass measurement to enhance metabolite identification and
      recent improvements in data acquisition and processing for accelerating
      metabolite identification are also described. Rounding out this review, we offer
      additional thoughts about the potential of alternative and less frequently used
      techniques such as LC-NMR/MS, CRIMS and ICPMS.

PMID- 16787161
TI  - The use of Qtrap technology in drug metabolism.
AB  - Advances in mass spectrometry continue to bring new and exciting capabilities to
      the study of drug metabolism. This review covers the hybrid linear ion trap -
      triple quadrupole mass spectrometer, the QTrap. While still a recent addition to
      the arsenal of mass spectrometry techniques available to the metabolism
      scientist, reports in the literature highlight the advantages of the system for
      metabolite identification. The system combines the selective scans of the triple
      quadrupole with the high speed, high sensitivity of the ion trap allowing
      metabolites to be found and characterized in a single scan. Additionally, the
      system has MS(3) and time delayed fragmentation scans that aid in structure
      elucidation. Since the fragmentation occurs in the collision cell of the triple
      quadrupole, the traditionally rich fragmentation of the collision cell
      fragmentation is preserved. In addition to helping to make traditional processes
      more efficient, work has been done that shows the potential of the instrument to
      change traditional DMPK approaches. Researchers have reported methods that allow
      for both qualitative analysis of circulating metabolites and quantification of
      parent drug within the same analysis. The approaches reported show how the
      instrument can be used to collect more information from every sample and
      potentially streamline typical drug metabolism assays.

PMID- 16787160
TI  - The role of mass spectrometry in biomarker discovery and measurement.
AB  - Recent advances in the biological and analytical sciences have led to
      unprecedented interest in the discovery and quantitation of endogenous molecules
      that serve as indicators of drug safety, mechanism of action, efficacy, and
      disease state progression. By allowing for improved decision-making, these
      indicators, referred to as biomarkers, can dramatically improve the efficiency of
      drug discovery and development. Mass spectrometry has been a key part of
      biomarker discovery and evaluation owing to several important attributes, which
      include sensitive and selective detection, multi-analyte analysis, and the
      ability to provide structural information. Because of these capabilities, mass
      spectrometry has been widely deployed in search for new markers both through the
      analysis of large molecules (proteomics) and small molecules (metabonomics). In
      addition, mass spectrometry is increasingly being used to support quantitative
      measurement to assist in the evaluation and validation of biomarker leads. In
      this review, the dual role of mass spectrometry for biomarker discovery and
      measurement is explored for both large and small molecules by examining the key
      technologies and methods used along the continuum from drug discovery through
      clinical development.

PMID- 16787162
TI  - Utility of the hybrid LTQ-FTMS for drug metabolism applications.
AB  - Fourier Transform Ion Cyclotron Mass Spectrometry (FTMS) provides the highest
      mass accuracy and mass resolving power of the currently available mass
      spectrometers. One of the main drawbacks in its use for absorption, distribution,
      metabolism and excretion (ADME) applications has been its incompatibility with
      standard HPLC columns and flow rates. Hybrid instruments, such as the LTQ-FT,
      provide the much needed bridge between the excellent performance and capabilities
      of the FT mass spectrometers and the well-established, tested and validated
      features of quadrupoles and ion traps. The hybrid instruments are compatible with
      standard HPLC flow rates, have high-throughput and automation compatibility, and
      also provide data dependant MSn. The ability to maintain the fidelity of an
      externally calibrated accurate mass measurement across an HPLC peak, where the
      analyte concentrations are rapidly changing, is a significant advance for this
      technology, as is the ability to perform data dependent MS/MS experiments on the
      chromatographic time scale. The MSn and accurate mass capabilities are routinely
      utilized to rapidly confirm the identification of expected metabolites or to
      elucidate the structures of unusual or unexpected metabolites. The combination of
      traditional high-flow chromatography and robust, externally calibrated accurate
      mass determination for both parent and product ions makes the LTQ-FTMS a very
      powerful analytical tool for the characterization of metabolites, identification
      of metabolic soft-spots and for metabonomics studies.

PMID- 16787163
TI  - Use of nano-electrospray for metabolite identification and quantitative
      absorption, distribution, metabolism and excretion studies.
AB  - Determination of the pharmacokinetics and metabolite identification have been an
      integral part of drug discovery and development to ensure that drugs have
      appropriate absorption, distribution, metabolism and excretion properties. Liquid
      chromatography interfaced with a mass spectrometer has greatly facilitated these
      studies. Nano-electrospray has distinct sensitivity advantages and the increased
      amount of time available to perform mass spectrometric experiments facilitates
      structural characterization of metabolites. The recently developed silicon chip
      based nano-electrospray devices are more practical than pulled capillaries. The
      use of these devices for the determination of pharmacokinetics and metabolite
      identification will be described and particular attention will be paid to the
      distinct advantages and disadvantages these devices offer.

PMID- 16787165
TI  - Nanoparticle-based diagnosis and therapy.
AB  - Nanoparticles are at the leading edge of the rapidly developing field of material
      science in nanotechnology with many potential applications in clinical medicine
      and research. Due to their unique size-dependent properties nanoparticles offer
      the possibility to develop both new therapeutic and diagnostic tools. The ability
      to incorporate drugs into nanosystems displays a new paradigm in pharmacotherapy
      that could be used for cell-targeted drug delivery. Nontargeted nanosystems such
      as nanocarriers that are coated with polymers or albumin and solid lipid
      particles have been used to transport a large number of compounds. However,
      nowadays drugs can be coupled to nanocarriers that are specific for cells and/or
      organs. Thus, drugs that are either trapped within the carriers or deposited in
      subsurface oil layers could be specifically delivered to organs, tumors and
      cells. These strategies can be used to concentrate drugs in selected target
      tissues thus minimizing systemic side effects and toxicity. In addition to these
      therapeutic options, nanoparticle-based "molecular" imaging displays a field in
      which this new technology has set the stage for an evolutionary leap in
      diagnostic imaging. Based on the recent progress in nanobiotechnology,
      nanoparticles have the potential to become useful tools as therapeutic and
      diagnostic tools in the near future.

PMID- 16787166
TI  - New insights into the molecular mechanisms of corticosteroids actions.
AB  - Corticosteroids produce a marked improvement in clinical parameters in most
      asthmatic patients; in contrast, corticosteroids have little effect on lung
      function measurements in patients with chronic obstructive pulmonary disease. By
      uncovering the reason for this paradox, it should be possible to implement
      treatment regimens that restore corticosteroid sensitivity. Corticosteroids exert
      their effects by binding to a cytoplasmic receptor, which is subjected to post
      translational modifications. Receptor phosphorylation may influence hormone
      binding and nuclear translocation, alter glucocorticoid receptor interactions and
      protein half-life. Other modifications such as nitration/nitrosylation may also
      affect glucocorticoid receptor function. Oxidative stress due to cigarette smoke
      may be a mechanism for the corticosteroid resistance observed in chronic
      obstructive pulmonary disease, as it enhances proinflammatory transcription and
      reduces glucocorticoid receptor-associated repressor functions. Therapies
      targeting these aspects of the glucocorticoid receptor activation pathway may
      reverse steroid resistance in patients with chronic obstructive pulmonary
      disease.

PMID- 16787167
TI  - Cytokines as targets in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease [COPD] is characterised by airflow
      limitation of peripheral airways that is not fully reversible and progressive and
      is associated with an abnormal inflammatory response of the lungs to noxious
      particles or gases. There is also intense airway wall remodelling and evidence of
      systemic inflammation. Increased interleukin [IL]-6, IL-1beta, tumor necrosis
      factor-alpha [TNF-alpha], GRO-alpha, MCP-1 and IL-8 levels are measured in
      sputum, with further increases during exacerbations. The bronchiolar epithelium
      over-expresses MCP-1, MIP-1alpha and IL-8. IL-8 can account for sputum neutrophil
      chemotactic activity. TNFalpha and IL-1beta stimulate macrophages to produce
      matrix metalloproteinase-9 [MMP-9], and bronchial epithelial cells to produce
      extracellular matrix glycoproteins. Increased expression of transforming growth
      factor-beta [TGFbeta) and epidermal growth factor [EGF] occurs in the epithelium
      and submucosal cells; gene array studies reveal an excess of TGFbeta1, CTGF and
      PDGFRA in COPD. TGFbeta and EGF activate proliferation of fibroblasts, while
      activation of the EGF receptor leads to mucin gene expression. Anti-cytokine
      therapy could be in the form of soluble receptors or by neutralising antibodies,
      small compounds blocking cytokine receptors or incomplete and non-activating
      cytokines, inhibitors of protein activation and inhibitors of signal transduction
      and transcription such as via inhibition of mitogen-activated protein kinases
      [MAPK] and of transcription factor, nuclear factor kappaB. Anti-IL-8 therapy has
      been tried with little effect on COPD, and current trials are on-going with TNF
      alpha inhibitors. Other treatments such as phosphodiesterase 4 inhibitors have
      anti-cytokine effects that may underlie their beneficial effects in COPD.

PMID- 16787168
TI  - Nuclear factor kappa B is a promising therapeutic target in inflammatory lung
      disease.
AB  - Nuclear factor kappa B (NF-kappaB) regulates the transcription of a wide array of
      gene products that are involved in the molecular pathobiology of the lung. Three
      lung cell types, epithelial cells, macrophages and neutrophils, have been shown
      to be involved in the generation of lung inflammation through signaling
      mechanisms that are dependent on activation of the NF-kappaB pathway. The basic
      molecular biology of the NF-kappaB activation pathway is well described, and
      approaches to modify this axis have involved inhibition of various components of
      the classical activation pathway, including ubiquitination and proteosomal
      degradation of IkappaB. Recently, there have been detailed characterizations of
      molecular mechanisms that involve reversible post-translational modification of
      RelA, including phosphorylation and acetylation that might be amenable to
      therapeutic interdiction. Alternately DNA decoy, antisense and siRNA technologies
      that interfere with NF-kappaB binding and inhibition of gene expression,
      respectively, of NF-kappaB proteins have been employed in experimental settings,
      but this has not been practically or effectively applied in human disease. A very
      promising approach, in our view, is inhibition of inhibitory kappa B kinases
      (IKK) since these appear to be highly specific for the NF-kappaB activation
      pathway and amenable to conventional small molecule pharmaceutical approaches.

PMID- 16787169
TI  - Chemokine receptors in chronic obstructive pulmonary disease (COPD).
AB  - Chronic obstructive pulmonary disease (COPD) is a debilitating disease
      characterized by recurrent episodes of leukocyte infiltration in the lung
      parenchyma causing progressive pulmonary tissue damage and loss of function.
      Recruitment of neutrophils and CD8+ T cells is linked to disease progression and
      is under control of chemotactic mediators produced in the inflamed COPD lung.
      Recent progress in elucidation of the molecular mechanisms that regulate
      migration of inflammatory cells into the lung has revealed interesting novel
      targets for therapeutic intervention in this disease. Chemokine receptors CXCR1
      and CXCR2 expressed on neutrophils and CXCR3 expressed on CD8+ T cells have been
      identified as potential therapeutic targets to prevent recruitment of pathogenic
      cells into the inflamed lung. However, the observation that chemokine receptors
      are also expressed and functional on various types of lung resident cells
      including epithelial and smooth muscle cells has raised new questions on the role
      played by chemokine receptors in COPD. These new findings suggest that chemokine
      receptor signalling could contribute to the adaptive response of lung tissue
      resident cells to the microenvironmental changes induced by inflammation. Thus,
      investigation of the role played by chemokine receptors in development of COPD
      remains a fertile area of research. Nevertheless, validation of chemokine
      receptor targets in COPD has proven a difficult challenge given the lack of
      predictive animal models of the disease and the still poorly defined etiology and
      pathogenesis.

PMID- 16787170
TI  - Targeting transcription: a new concept of anti-inflammatory therapy of airway
      diseases.
AB  - Most pathological conditions that result in human diseases are associated with
      altered gene expression. With the advent of new technologies that might control
      gene expression and a broader knowledge of transcription factors and pathways,
      new strategies have emerged that offer promising first results for therapeutical
      and experimental purposes. This review will focus on different inflammatory
      conditions of the lung, in which targeting the transduction of involved genes
      have been successfully attempted.

PMID- 16787171
TI  - Targeting mitogen-activated protein kinases for asthma.
AB  - Allergic asthma is a chronic airway inflammatory disorder attributable to T
      helper 2 cell responses together with other inflammatory cells such as mast
      cells, B cells and eosinophils, and pro-inflammatory cytokines and chemokines.
      Mitogen-activated protein kinase (MAPK) signaling cascades have been shown to be
      important in the differentiation, activation, proliferation, degranulation and
      migration of various immune cells, and airway smooth muscle and epithelial cells.
      In mammal, MAPK signaling modules are divided into at least 3 groups:
      extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal
      kinase (JNK). Each MAPK module plays a discrete yet complementary role in
      accentuating allergic airway inflammation. Cumulative evidence reveals potential
      anti-inflammatory activities of MAPK inhibitors in a variety of in vitro models
      of inflammation. Recently, the anti-inflammatory effects of MAPK kinase inhibitor
      (U0126), p38 MAPK inhibitors (SB239063 and respirable p38alpha MAPK antisense
      oligonucleotide) and JNK inhibitor (SP600125) have been demonstrated in in vivo
      animal models of asthma. Development of inhibitors targeting at MAPK could be an
      attractive strategy for the treatment of asthma.

PMID- 16787172
TI  - Adenosine receptors as promising therapeutic targets for drug development in
      chronic airway inflammation.
AB  - A growing body of evidence has emerged in support of a pro-inflammatory role for
      adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the
      airways such as asthma and COPD. The demonstration that adenosine enhances mast
      cell allergen-dependent activation, the notion that elevated levels of adenosine
      are present in chronically inflamed airways, and the results from exposure
      studies of nebulised adenosine showing dose-dependent bronchoconstriction in
      subjects with asthma and COPD, emphasise the importance of adenosine in the
      initiation, persistence and progression in these common inflammatory disorders of
      the airways. Adenosine exerts its manifold biological activities by interacting
      with at least four adenosine receptor subtypes. Selective activation or blockade
      of these sites is being exploited by the pharmaceutical industry in an attempt to
      generate novel therapies for asthma and COPD. This review article intends to
      address the potential role of adenosine in asthma and to put forward the idea
      that drugs that have been developed to selectively activate or downregulate
      adenosine receptor subtypes may constitute a considerable advance in the
      management of chronic airway inflammation.

PMID- 16787173
TI  - Antioxidant therapeutic targets in COPD.
AB  - Oxidative stress and chronic inflammation are important features in the
      pathogenesis of chronic obstructive pulmonary disease (COPD). Oxidative stress
      has important consequences for several elements of lung physiology and for the
      pathogenesis of COPD, including oxidative inactivation of antiproteases and
      surfactants, mucus hypersecretion, membrane lipid peroxidation, alveolar
      epithelial injury, remodeling of extracellular matrix, and apoptosis. Therefore,
      targeting oxidative stress with antioxidants or boosting the endogenous levels of
      antioxidants is likely to be beneficial in the treatment of COPD. Antioxidant
      and/or anti-inflammatory agents such as thiol molecules (glutathione and
      mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenol
      (curcumin-diferuloylmethane, a principal component of turmeric), resveratrol (a
      flavanoid found in red wine), green tea (theophylline and epigallocatechin-3-
      gallate), ergothioneine (xanthine and peroxynitrite inhibitor), quercetin,
      erdosteine and carbocysteine lysine salt, have been reported to control NF-kappaB
      activation, regulation of glutathione biosynthesis genes, chromatin remodeling
      and hence inflammatory gene expression. Specific spin traps such as alpha-phenyl
      N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), manganese (III)
      meso-tetrakis (N,N'-diethyl-1,3-imidazolium-2-yl) porphyrin (AEOL 10150 and AEOL
      10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette
      smoke-induced inflammatory responses in vivo. Since a variety of oxidants, free
      radicals and aldehydes are implicated in the pathogenesis of COPD it is possible
      that therapeutic administration of multiple antioxidants will be effective in the
      treatment of COPD. Various approaches to enhance lung antioxidant capacity and
      clinical trials of antioxidant compounds in COPD are discussed.

PMID- 16787175
TI  - The vasculature as a target in the treatment of pulmonary emphysema.
AB  - Pulmonary emphysema, a major component of chronic obstructive pulmonary diseases,
      is a highly prevalent progressive tissue-destructive disease, with no effective
      treatments. The interplay between inflammation, matrix proteolysis, oxidative
      stress and apoptosis might account for the irreversible progression of the
      disease. Recent investigations have underlined the importance of the lung
      vasculature in the pathobiology of chronic obstructive pulmonary diseases
      offering new therapeutic strategies. This review will focus on the pulmonary
      microvessels as a target in the treatment of pulmonary emphysema.

PMID- 16787174
TI  - Nitric oxide synthase (NOS) as therapeutic target for asthma and chronic
      obstructive pulmonary disease.
AB  - In the respiratory tract, NO is produced by residential and inflammatory cells.
      NO is generated via oxidation of L-arginine that is catalysed by the enzyme NO
      synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS),
      inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the
      constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules
      (nitrosothiols) are able to modulate bronchomotor tone. NO derived from the
      inducible isoform of NO synthase, up-regulated by different cytokines via NF
      kappaB-dependent pathway, seems to be a pro-inflammatory mediator with
      immunomodulatory effects. The production of NO under oxidative stress conditions
      secondarily generates strong oxidising agents (reactive nitrogen species) that
      may amplify the inflammatory response in asthma and COPD. Moreover, NO can be
      exhaled and levels are abnormal in stable atopic asthma and during exacerbations
      in both asthma and COPD. Exhaled NO might therefore be a non-invasive tool to
      monitor the underlying inflammatory process. It is suggested that NOS regulation
      provides a novel target in the prevention and treatment of chronic inflammatory
      diseases of the airways such as asthma and COPD.

PMID- 16787176
TI  - Antimicrobial peptides in COPD--basic biology and therapeutic applications.
AB  - A large number of studies have implicated activation of innate immune mechanisms
      in the pathogenesis of chronic obstructive pulmonary disease (COPD). Accumulation
      of inflammatory cells, chemokines and pro-inflammatory cytokines is a hallmark of
      activation of these mechanisms, but only a few studies have focussed on
      antimicrobial peptides in COPD. These peptides are a central component of innate
      immunity, and airway epithelial cells and neutrophils in the lung are the main
      cellular sources. In addition to their direct antimicrobial action, antimicrobial
      peptides have been shown to display a variety of activities that may implicate
      them in the pathogenesis of COPD. This is based on the observation that they not
      only contribute to defense against respiratory pathogens that have been
      associated with COPD, but may also contribute to the influx of inflammatory
      cells, activation of adaptive immunity and epithelial remodeling. The aim of this
      review is to provide an update on the basic biology of antimicrobial peptides in
      the lung, with a focus on their putative role in COPD. In addition, the
      implication of this knowledge for future treatment of COPD is discussed.

PMID- 16787177
TI  - Proteases and their role in chronic inflammatory lung diseases.
AB  - Proteases play an essential role in modulating the turnover of extracellular
      matrix. Furthermore, they are involved in the processing of various proteins thus
      regulating fundamental cellular functions such as apoptosis, cells growth and
      activation, protein secretion and phagocytosis. At the tissue and organ levels,
      proteases influence mechanisms including cell migration and invasion, cellular
      interactions and signal transduction as well as tissue formation and
      stabilization. Proteases are classified based on their catalytic mechanisms into
      serin, aspartic, metallo, threonin and cysteine proteases and are localized
      extracellularly, at the cellular surface, in the cytoplasm of cells or within
      specific subcellular structures such as lysosomes. The present review focuses on
      the specific functions of lysosomal cysteine proteases and the potential effects
      of modulators of cysteine protease activity.

PMID- 16787178
TI  - Leptin: a promising therapeutic target with pleiotropic action besides body
      weight regulation.
AB  - Leptin seems to regulate various physiological mechanisms besides body weight.
      Leptin plays a role in vascular biology and pathology as well as renal function.
      In addition, leptin has been implicated in the regulation of fertility and
      reproduction. The effect of pharmaceutical agents on circulating plasma leptin
      levels has been assessed. Among the drugs investigated are glitazones, statins,
      fibrates, serotonin reuptake inhibitors and cannabinoid-1 receptor antagonists.
      Since these agents are used to treat pathological conditions there is a potential
      role for leptin in these states. The degree of involvement of leptin in several
      pathophysiological states needs to be defined to aid in the development of
      potentially useful therapeutic agents.

PMID- 16787179
TI  - Histone deacetylase inhibitors as potent modulators of cellular contacts.
AB  - Histone deacetylase inhibitors are nowadays considered as promising anti-cancer
      drugs, as they interfere with several key steps of tumor development and
      progression, both in vitro and in vivo. Less attention has been paid to their
      impact on cell junctions. Nevertheless, cell junctions are gatekeepers in the
      management of tissue homeostasis, and their aberrant expression and functioning
      is observed in all aspects of cancer biology. The present review provides a state
      of the art of the current knowledge concerning the effects of histone deacetylase
      inhibitors on cell junctions. Besides an updated theoretical basis, we also
      exemplify its actual relevance in cancer therapy.

PMID- 16787181
TI  - The history of the HSV amplicon: from naturally occurring defective genomes to
      engineered amplicon vectors.
AB  - We have derived the HSV amplicon vector in 1981/1982 after elaborate experience
      with "defective viruses", arising spontaneously in viral stocks propagated at
      high multiplicities of infection (m.o.i.). The defective viruses were found to
      contain large concatemeric genomes with repeat units of limited complexity. We
      employed cloned defective genome repeats to generate the "amplicon" vectors,
      which in the presence of helper virus replicate to produce packaged large
      concatemeric genomes, transmissible to uninfected cells. The cloned amplicons
      were then employed to fine map and analyze the signals essential for amplicon
      propagation: (i) A DNA replication origin, producing concatemeric genomes by
      rolling circle replication. Three DNA replication origins were identified in the
      HSV genome. (ii) Signals termed pac-1 and pac-2, directing a measuring function
      for coordinate cleavage of the concatemeric genomes and their packaging as full
      size (150 kb) genomes. Using amplicons, foreign genes of large sizes could be
      linked to less than 1 kb of the cis-acting HSV DNA sequences and become amplified
      in packaged defective genomes, transmissible to new cells. The transgenes are
      expressed efficiently, due to sequence reiterations. Large quantities of vectors
      can be produced in vitro. The amplicons are attractive vectors for use as non
      integrating gene delivery vectors. The packaging signals pac-1 and pac-2 are well
      conserved in different herpesviruses and amplicons with a DNA replication origin
      and cleavage and packaging signals have been produced in additional
      herpesviruses. Depending on amplicon-host cell combination, the vectors can be
      employed with and without mutated helper virus(es) to obtain high gene
      expression, and desired effect on the target cell. In the absence of helper
      virus, the defective virus produced is limited for spread in the targeted cells.
      We expect that new vectors employing state of the art transgenes, will be
      developed to generate amplicon based concatemeric defective viruses capable of
      efficient expression of these genes.

PMID- 16787182
TI  - DNA-based methods to prepare helper virus-free herpes amplicon vectors and
      versatile design of amplicon vector plasmids.
AB  - The herpes simplex virus (HSV) amplicon vector is a versatile plasmid-based gene
      delivery vehicle with a large transgene capacity (up to 150 kb) and the ability
      to infect a broad range of cell types. The vector system was originally developed
      by Frenkel and her colleagues in 1980. Ever since, a great deal of effort by
      various investigators has been directed at minimizing the toxicity associated
      with the inevitable contamination by helper virus. In 1996, Fraefel and his
      colleagues successfully devised a cosmid-based packaging system that was free of
      contamination by helper virus (so-called helper virus-free packaging), which
      utilized as helper a set of 5 overlapping cosmid clones that covered the entire
      HSV genome, which lacked the DNA packaging/cleavage signals. With the helper
      virus-free system, broader applications of the vector became possible. Cloning of
      the entire HSV genome in bacteria artificial chromosome (BAC) plasmids enabled
      stable maintenance and propagation of the helper HSV genome in bacteria. It also
      allowed for the development of BAC-based helper virus-free packaging systems. In
      this article, we review various versions of DNA-based methods to prepare HSV
      amplicon vectors free of helper virus contamination. We also examine recent
      advances in vector design, including methods of vector construction, hybrid
      amplicon vectors, and the infectious BAC system. Future directions in improving
      packaging systems and vector designs are discussed.

PMID- 16787183
TI  - Chimeric herpes simplex virus/adeno-associated virus amplicon vectors.
AB  - Chimeric or hybrid herpes simplex virus type 1/adeno-associated virus amplicon
      vectors combine the large transgene capacity of HSV-1 with the potential for site
      specific genomic integration and stable transgene expression of AAV. These
      chimeric vectors have been demonstrated to support transgene expression for
      significantly longer periods than standard HSV-1 amplicons. Moreover, HSV/AAV
      hybrid vectors can mediate integration at the AAVS1 pre-integration site on human
      chromosome 19 at a relatively high rate, although random integration has also
      been observed. One major remaining hurdle of HSV/AAV hybrid vectors is the low
      packaging efficiency and titers when AAV rep sequences are included in the
      amplicon vector. In the conditions prevalent during the replication/packaging of
      HSV/AAV hybrid amplicons into HSV-1 virions, in particular the presence of HSV-1
      replication factors and AAV Rep protein, at least three different viral origins
      of DNA replication are active: the HSV-1 ori, the AAV inverted terminal repeats
      (ITRs), and the p5 promoter/ori driving expression of the AAV rep gene. A
      detailed understanding of the properties of these origins of DNA replication and
      the molecular mechanisms of interactions between them, may allow designing novel
      hybrid vectors that allow the efficient and precise integration of large
      transgenes in the human genome.

PMID- 16787184
TI  - Delivery of large genomic DNA inserts >100 kb using HSV-1 amplicons.
AB  - The principal aim of gene therapy for recessive genetic diseases is to supplement
      the loss of function of an endogenous gene. For the treatment of many diseases
      regulation of transgene expression at physiological levels, expression of
      multiple splice variants, and correct tissue specificity are of utmost importance
      for effective therapy. We therefore believe the use of a complete genomic locus,
      in which the native promoter and regulatory regions drive and control expression,
      is an elegant and effective alternative to traditional complementary DNA (cDNA)
      vectors utilising heterologous promoters. Viral vectors have proved, over the
      years, to be an effective means of gene delivery in vitro and in vivo, but the
      size of complete genomic loci precludes their use in most viral systems. One
      notable exception comprises the amplicon-type vectors based on human
      herpesviruses, such as the herpes simplex virus type I (HSV-1) amplicon vector.
      The large genome of HSV-1 (152 kb) confers upon HSV-1 amplicons a very large
      transgene capacity sufficient to accommodate approximately 95% of human genomic
      loci. The combination of the large transgene capacity, a broad range of cell
      tropism, and the ability to infect dividing and non-dividing cells makes HSV-1
      amplicons an excellent vector system to develop for the delivery of large genomic
      loci. Here we review recent work which has shown that HSV-1 amplicons can be used
      for the delivery and expression of large genomic inserts >100 kb to cells in
      culture to rescue phenotypes in cellular models of genetic disease. We then
      discuss applications for high capacity HSV-1 amplicons in vivo and their
      potential to facilitate the use of large genomic inserts in gene therapy
      treatment regimes.

PMID- 16787185
TI  - HSV amplicons: neuro applications.
AB  - Strategies that employ HSV amplicon vectors in the prevention and/or amelioration
      of pathogenic states afflicting the central nervous system (CNS) have been
      extensively documented in preclinical disease models. The versatility of the HSV
      amplicon platform allows for the implementation of therapeutic approaches that
      require expression of genes exhibiting neuroprotective or neuroplastic
      activities, or even applications that necessitate the elaboration of antigen
      specific immune responses to pathogenic proteins/structures harbored within the
      CNS. This discourse highlights the successes and challenges encountered using HSV
      amplicon vectors as tools for the dissection of neural network function and as
      therapeutics directed against a variety of neurologic disorders.

PMID- 16787186
TI  - Amplicon vectors as outstanding tools to study and modify cognitive functions.
AB  - This review summarizes recent data on the use of HSV-1-based amplicon vectors for
      in vivo gene delivery to the brains of rats and mice to study and modify
      behaviour. Here we describe studies that have focused on cognitive functions like
      learning and memory. In addition, the use of amplicons in other behavioural
      studies, like addiction, social interaction, anxiety and stress, will be briefly
      updated. Several remarkable findings have been achieved, thanks to the use of
      these very efficient and non-toxic naturally neurotropic vectors, most
      particularly the consistent observation that genetic manipulation of a rather
      limited number of neurons in restricted regions of the brain, could result in
      significant behavioural changes, a notion that is therefore emerging as a common
      unifying hypothesis, thanks to these works.

PMID- 16787187
TI  - HSV amplicon vectors for cancer therapy.
AB  - HSV amplicon vectors provide a unique tool in the armamentarium of weapons for
      treatment of cancer. Their large capacity (up to 150 kb) allows incorporation of
      multiple and large transgenes, including whole gene loci, as well as components
      of other viruses to control the fate of transgenes in the host cells. Means have
      been developed to achieve heritable transmission of transgenes in tumor cells by
      episomal replication or genomic integration. Therapeutic transgenes incorporated
      into amplicon vectors have included anti-angiogenic agents, immune enhancing
      proteins, prodrug activating enzymes, and apoptosis-inducing factors, as well as
      inhibitory RNAs for tumor-associated messages. Perks of this vector system
      include the ability to combine amplicon vectors with oncolytic HSV recombinant
      vectors to extend the therapeutic range and to target non-dividing as well as
      dividing tumor cells. Tumor vaccination is favored by the high infectivity of
      dendritic antigen-presenting cells with HSV vectors, and the vectors themselves
      appear to have intrinsic immune enhancing properties. Promoter manipulation can
      be used to target therapeutic gene expression to specific tumor cell types and to
      achieve drug regulated transgene expression. Further, amplicon vectors can be
      used to convert tumor cells into packaging cells for retrovirus and adeno
      associated virus vectors, thus generating vectors on site. Amplicon vectors have
      also proven to be a versatile tool to explore imaging modalities to monitor gene
      delivery and tumor responses to therapeutic intervention.

PMID- 16787188
TI  - HSV-1 amplicon vectors are an efficient gene transfer system for skeletal muscle
      cells.
AB  - HSV-1 amplicon vectors have been considered as a promising gene delivery system
      for gene therapy of skeletal muscle diseases, due to the ability to infect non
      dividing cells such as differentiated muscle cells, and to accommodate large
      transgenes such as the 14-kb dystrophin cDNA. Studies revealed that HSV-1
      amplicons can transduce cultured differentiated and undifferentiated muscle cells
      with high efficiency. Studies also revealed that HSV-1 amplicons are capable of
      delivering at least 23-kb transgene DNA, including the full-length dystrophin
      cDNA into muscle cells. The combination of high transduction efficiency, the
      ability to accommodate large constructs and ease of manipulation makes HSV-1
      amplicons an ideal gene delivery tool for the study of muscle ion channels in
      which gene transduction is frequently employed in cultured muscle cells that are
      resistant to all the transfecting reagents. However, intramuscular injection of
      HSV-1 amplicons has been proven inefficient in mature muscles. Evidence has shown
      that this is mainly because the basal membrane that sheaths each myofibers blocks
      HSV-1 virions from myofiber cell surface receptors. This result led to the
      conclusion that HSV-1 amplicons are more suitable for ex vivo manipulation of
      diseased muscle progenitors or stem cells for autologous cell therapy than in
      vivo intramuscular injection. Efforts to confer stable transduction ability on
      amplicons have made progress. A new generation of HSV/AAV hybrid amplicons has
      been shown to be capable of integrating large transgenes into the AAVS1 site of
      the human genome, thus, holding potential to achieve a safe and lasting gene
      transduction in human muscle cells.

PMID- 16787189
TI  - Amplicons as vaccine vectors.
AB  - HSV-1 amplicon vectors efficiently transduce cultured antigen-presenting cells
      (APC), including both human and murine dendritic cells as well as primary human
      chronic lymphocytic leukemia (CLL) B cells. Helper-free amplicons have been shown
      to be especially well-suited for this purpose, since they do not impair the
      antigen-presenting functions of these target cells. In vivo, amplicon vectors
      have been used in preclinical studies aimed at the development of therapeutic
      cancer vaccines, as well as vaccines for Alzheimer's disease, and selected
      microbial pathogens. Studies in small animal model systems have shown that ex
      vivo transduction of irradiated tumor cells with amplicon vectors encoding
      immunomodulatory cytokines such as IL-2 or GM-CSF can elicit protective responses
      against a tumor challenge. In an experimental model for cancer immunotherapy,
      direct transduction of preformed tumors with vectors encoding CD40L resulted in
      slowed tumor growth or tumor eradication. Other studies have examined the ability
      of amplicons to elicit immune responses against encoded antigens, and have shown
      that strong cellular immune responses can be generated against amplicon encoded
      HIV-1 antigens in mice. Thus, amplicon vectors have shown significant promise as
      vaccine vectors in a range of settings. These promising initial findings
      highlight the need to perform additional studies, including experiments to
      evaluate the immunogenicity of amplicon vectors in additional animal models,
      possibly including nonhuman primates. Overall, amplicon vectors offer compelling
      advantages when compared to other vaccine-delivery platforms, which include the
      capacity to incorporate a very large transgene payload and the potential to
      efficiently transduce mucosal surfaces. It will be important to design future
      studies to directly test and exploit these features of the amplicon system. The
      next few years therefore promise to be an exciting and important period in the
      development of amplicons as vaccine vectors.

PMID- 16787190
TI  - HSV-1 based amplicon vectors as an alternative system for the expression of
      functional HCV proteins.
AB  - The lack of efficient systems for the propagation of the hepatitis C virus in
      vitro, in the past decade, led to the development of several heterologous
      expression systems for the study of the HCV proteins and the HCV life cycle. HSV
      1 amplicon vectors encoding the HCV structural and some of the non structural
      proteins were generated initially for the expression of high levels of these
      proteins into mammalian cells. The recent developments in the production of
      amplicon vectors, allowing the elimination of the contaminating helper HSV-1
      virus have given a novel impulse in the study of these vectors as possible
      vaccine candidates. In this review, an extensive list of the existing amplicon
      vectors expressing HCV proteins is provided, together with a brief overview of
      the results obtained by these studies.

PMID- 16787191
TI  - Characterization of the lymphotropic amplicons-6 and tamplicon-7 vectors derived
      from HHV-6 and HHV-7.
AB  - Amplicon-6 and Tamplicon-7 are novel non-integrating vectors derived from the
      lymphotropic Human Herpesviruses 6 and 7 (HHV-6 and HHV-7). In the presence of
      helper viruses the amplicon vectors replicate to yield packaged defective genomes
      of size approximately 150 kb and consisting of multiple repeat units containing
      (i) the oriLyt DNA replication origin (ii) the pac-1 and pac-2 cleavage and
      packaging signals (iii) bacterial plasmid DNA sequences (iv) the chosen
      transgene(s). Employing CD46 as a receptor HHV-6 gains entry into varied cells,
      including lymphocytes and dendritic cells, whereas HHV-7 employs the CD4 receptor
      to target CD4+ cells. The amplicon-based vectors have facilitated the
      characterization of viral DNA replication and packaging. Following
      electroporation and helper virus superinfection, the vectors can be transmitted
      as cell associated and as cell-free virions secreted into the medium. Analyses by
      flow cytometry have shown good cell spread and efficient gene expression.
      Exemplary transgenes have included: (i) The Green Fluorescence Protein (GFP) (ii)
      Genes for potential use in anti-viral vaccination e.g., the HSV-1 glycoprotein D
      (gD) with and without the trans-membrane region, expressed intracellularly, at
      the cell membrane or as secreted proteins. (iii) Tumor cell antigens. (iv)
      Apoptotic genes for development of oncolytic vectors. Due to their cell tropism,
      their structure as concatemeric genomes, with less than 1.5 kb of viral DNA
      sequences, the HHV-6 and 7 amplicons have the potential to become unique vectors
      for immunization and lymphotropic gene therapy.

PMID- 16787192
TI  - The effects of prostaglandin E-1 in patients with intermittent claudication.
AB  - Aim of the study is to evaluate the effects of Prostaglandin E-1 (PGE-1) in
      patients with peripheral arterial disease (PAD) at the 2nd b stage Fontaine's
      classification. The study, controlled, single blinded, enrolled 123 patients with
      intermittent claudication that were randomised in two groups; the first group
      received a treatment with PGE-1 while the second one received a pentoxifylline
      buflomedil association by venous infusion. We evaluated: Pain Free Walking
      Distance (PFWD), Maximum Walking Distance (MWD), Rest Flow (RF), Peak Flow (PF),
      Basal (BVR) and Minimal Vascular Resistance (MVR) with a strain gauge
      plethysmograph, Resting Flow (RF), Peak Flow (PF), time to reach the Peak Flow
      (tPF) and time to recovery of the base values (tRF) with laser Doppler flowmeter.
      After a four weeks treatment, we observed an increase of 370% about PFWD and of
      260% in the MWD in patients treated with PGE-1; the other group showed an
      increase of 110% and 118% respectively. Moreover, the patients of the first group
      showed a significant increase regarding the plethysmographic Peak Flow (from
      9.75+/-1.37 to 16.21+/-1.75, p<0.001), greater than the one observed in the
      second group (from 9.53+/-1.41 to 13.47+/-1.53, p<0.05); also the laser Doppler
      parameters showed a significant reduction, more evident in the first group (tPF
      from 23.0+/-7.5 to 10.5+/-4.9, p<0.001; tRF from 73.5+/-22.7 to 48.3+/-13.5,
      p<0.001) than in the second one.

PMID- 16787193
TI  - Prevention of myocardial damage during coronary intervention.
AB  - Myocardial injury during coronary intervention occurs in 10-40% of cases and is
      often characterized by a slight increase of markers of myocardial necrosis,
      without symptoms, electrocardiographic changes or impairment of cardiac function.
      However, even small increases of creatine kinase-MB levels are expression of a
      true and detectable infarction, and may be associated with higher follow-up
      mortality. The cause of CK-MB elevation in case of procedural complications
      (dissection, transient vessel closure, no reflow, side branch occlusion etc.) is
      obvious; however, most cases of minor CK-MB elevation occur in patients with
      uncomplicated procedure with excellent final angiographic results. It has been
      suggested that the main mechanism explaining occurrence of myocardial necrosis
      during otherwise successful coronary interventions may be distal
      microembolization of plaque components, an enhanced inflammatory state or due to
      total plaque burden and/or to plaque instability. Different treatments have been
      proposed to prevent myocardial injury during coronary intervention, including
      nitrate infusion, intracoronary beta-blockers, adenosine, clopidogrel and
      IIb/IIIa inhibitors, but none of those (apart from the use of IIb/IIIa
      inhibitors) has been routinely introduced in clinical practice. We performed the
      ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty)
      trial, i.e. the first prospective, randomised, placebo controlled study to
      evaluate effects of 7 days of pre-treatment with a fixed dose of atorvastatin (40
      mg/day) on post-procedural release of markers of myocardial damage in patients
      with stable angina undergoing percutaneous intervention. In this study therapy
      with atorvastatin has been associated with 80% risk reduction on the occurrence
      of peri-procedural myocardial infarction, as well as with significant reduction
      of post-intervention peak levels of all markers of myocardial damage. The
      mechanisms underlying the beneficial effects of atorvastatin may be an
      inflammatory action reducing myocardial necrosis due to microembolization, an
      improvement of endothelial function on microcirculation, and direct protection of
      myocardium.

PMID- 16787194
TI  - Cyclooxygenase-2 inhibitors: a painful lesson.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) represent a clinically important
      class of agents. NSAIDs are commonly used in treatment of conditions such as
      headache, fever, inflammation and joint pain. Complications often arise from
      chronic use of NSAIDs. Gastrointestinal (GI) toxicity in the form of gastritis,
      peptic erosions and ulcerations and GI bleeds limit usage of NSAIDs. These
      toxicities are thought to be due to cyclooxygenase (COX)-1 blockade. COX-1
      generates cytoprotective prostanoids such as prostaglandin (PG) E2 and
      prostacyclin (PGI2). COX-2 inhibitors, commonly referred to as coxibs, were
      developed to inhibit inflammatory prostanoids without interfering with production
      of COX-1 prostanoids. Concerns over cardiovascular safety, however, have evolved
      based on the concept of inhibition of COX-2-derived endothelial prostanoids
      without inhibition of platelet thromboxane A2, leading to increased
      cardiovascular risk. The Celecoxib Long-Term Arthritis Safety Study (CLASS) trial
      did not show a significant increase in cardiovascular risk for celecoxib
      (Celebrex), but results of the Vioxx Gastrointestinal Outcomes Research (VIGOR)
      study showed an increased cardiovascular risk with long-term daily usage of
      rofecoxib in patients with rheumatoid arthritis. The Adenomatous Poly Prevention
      on Vioxx (APPROVe) trial further evaluated cardiovascular effects of rofecoxib
      and recently led to removal of this drug from the marketplace. Coxibs affect
      renal function via blockade of normal COX-2 functions. COX-2 expression increases
      in high renin states and in response to a high-sodium diet or water deprivation.
      PGI2 and PGE2 are the most important renal prostanoids. PGI2 inhibition results
      in hyperkalemia. PGE2 inhibition results in sodium retention, which leads to
      hypertension, peripheral edema and potentially exacerbation of heart failure.
      This review article discusses beneficial and deleterious effects associated with
      prostanoids produced by COX-1 and COX-2 in various organs and how blockade of
      these products translates into clinical medicine.

PMID- 16787195
TI  - Regulatory mechanisms of cardiac development and repair.
AB  - The heart originates from bilateral primordia that eventually fuse in the
      embryonic midline leading to a linear tube. Soon after, the heart bends to the
      right and atrial and ventricular chambers are formed. Progressively each
      embryonic compartment initiates a process of septation that eventually leads to a
      four chambered heart with a double circuitry and synchronous contraction. During
      these developmental events, the growth of the heart and in particular of its
      myocardial component gradually increases. However, as the heart gets into its
      mature stage, myocardial growth ceases and concomitantly the myocardium looses
      its proliferative capacity. In the adult human population, the most frequent
      cardiac pathologies emanate from a decompensated lost of myocardial function.
      Therapeutical approaches aiming to add or replace new myocytes to the failing
      heart are thus highly desired. Embryonic stem cells have a high capacity to give
      rise to multiple cell types, including myocardial cells, opening new
      therapeutical possibilities. Unexpectedly discrete adult cell populations have
      also shown a greater cell plasticity than previously thought, earning therefore
      much attention as therapeutic targets. These observations have launched initial
      clinical trials with great hope of clinical benefit. However, it is essential in
      this respect to initially understand, and eventually control myogenic cell fate
      determination. Developmental biology of the heart provides a very suitable model
      for this end. Over the last decade there has been a considerable advance in the
      understanding of the molecular mechanisms that lead to the determination of the
      cardiomyocyte lineage and the regulatory mechanisms by which morphogenesis of the
      heart takes place. Growth factor signalling and transcriptional events
      controlling cardiac myogenesis have been progressively unravelled. In this review
      we aim to summarise current data concerning the cardiomyogenic cell fate
      determination pathways occurring during the natural process of cardiogenesis as
      compared to the myogenic lineages obtained from embryonic and adult stem cells.
      Identification of key elements provides important resources to which drugs can be
      targeted and eventually can result in promising tools to control and expand
      cardiomyocyte determination.

PMID- 16787196
TI  - Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for
      patients with acute myocardial infarction?
AB  - Reperfusion of ischemic myocardium after acute myocardial infarction (AMI)
      induces a local activation of inflammatory reactions that results in
      ischemia/reperfusion (I/R)-injury. I/R-injury contributes considerably to the
      total cell damage in the heart after AMI. Secretory phospolipase A2-IIA (sPLA2
      IIA), C-reactive protein (CRP) and complement are inflammatory mediators that
      have been demonstrated to play key roles in I/R injury. From studies by us and
      others a mechanism emerged in which sPLA2-IIA binds to reversibly damaged
      cardiomyocytes and subsequently induces cell death, partly by potentiating
      binding of CRP and subsequent complement activation. Next to this, sPLA2-IIA also
      has a direct toxic effect, independent of CRP or complement. Therefore, these
      studies indicate a crucial role of inflammatory mediators in ischemia/reperfusion
      injury. This review will focus on the pathogenic effects of sPLA2-IIA, CRP and
      complement and on the putative therapeutic effects of inhibitors of these
      inflammatory mediators in acute myocardial infarction.

PMID- 16787197
TI  - Physiological significance and therapeutic potential of adrenomedullin in
      pulmonary hypertension.
AB  - Adrenomedullin (ADM) is a potent vasodilator peptide that was originally isolated
      from human pheochromocytoma. Its vasodilatory effect is mediated by cyclic
      adenosine 3',5'-monophosphate- and nitric oxide-dependent mechanisms. Earlier
      studies have demonstrated that ADM is secreted from various tissues, including
      vessels, heart, and lungs. In addition, there are specific receptors for ADM in
      the lungs. Plasma ADM level is elevated in proportion to the severity of
      pulmonary hypertension, and circulating ADM is partially metabolized in the
      lungs. These findings suggest that ADM plays an important role in the regulation
      of pulmonary vascular tone. Administration of ADM by intravenous or intratracheal
      delivery significantly decreased pulmonary arterial pressure and pulmonary
      vascular resistance in patients with pulmonary arterial hypertension.
      Furthermore, we have recently developed a new therapeutic strategy using ADM gene
      modified endothelial progenitor cells (EPC). Intravenously administered ADM gene
      modified EPC were incorporated into lung tissues and attenuated monocrotaline
      induced pulmonary hypertension in rats. In addition, ADM has angiogenic and anti
      apoptotic activities via activation of Akt and/or mitogen-activated protein
      kinase. These findings suggest that ADM may act not only as a vasodilator but
      also as a vasoprotective factor. Thus, ADM may be a promising endogenous peptide
      for the treatment of pulmonary hypertension.

PMID- 16787198
TI  - Uremia, atherothrombosis and malnutrition: the role of L-arginine-nitric oxide
      pathway.
AB  - The uraemic syndrome is a complex condition that results from an accumulation of
      multiple waste compounds, combined with failure of the endocrine and homeostatic
      functions of the kidney in end-stage chronic renal failure (CRF) patients.
      Recently it has become clear that uraemia is a microinflammatory condition with a
      significant increase in inflammation markers. Malnutrition is a common
      pathological condition which exacerbates cardiovascular mortality in uraemic
      patients. Inadequate diet and a state of persistent catabolism play major roles
      in uraemic malnutrition, yet the underlying mechanisms have not been completely
      clarified. Malnourished patients present elevated levels of circulating
      cytokines, further aggravating the oxidative and inflammatory characteristics of
      uraemia. It has been suggested that abnormalities in nitric oxide bioactivity,
      coupled with malnutrition and inflammation, may contribute to increased incidence
      of atherothrombotic events in uraemia. Amongst the earliest indications of
      nutritional deficiency are low concentrations of plasma amino acids, including L
      arginine, the precursor for nitric oxide (NO) synthesis. Atherosclerosis is an
      inflammatory disorder and NO is an important mediator of inflammation. There is a
      close association between thrombosis and platelet aggregation, and NO is involved
      in all stages of platelet activation. L-arginine inhibits platelet aggregation
      both in vitro and in vivo, while L-NMMA (NG-monomethyl-L-arginine), an endogenous
      L-arginine analogue and inhibitor of NO synthase (NOS), increases platelet
      activation and adhesion. The majority of studies in animal models and human
      patients indicate that the systemic production of NO is increased in uraemia. CRF
      patients show reduced plasma concentration of L-arginine, and the enhancement of
      L-arginine transport is essential to maintain increased NO synthesis in platelets
      taken from these patients. The present review provides an overview of recent
      advances in the understanding of the association among malnutrition, chronic
      inflammation and the L-arginine-nitric oxide pathway in uraemic patients, and
      related potential interventions that could improve clinical outcome in chronic
      renal failure.

PMID- 16787199
TI  - Dietary small molecules and large-scale gene expression studies: an experimental
      approach for understanding their beneficial effects on the development of
      malignant and non-malignant proliferative diseases.
AB  - Epidemiological studies have repeatedly demonstrated a correlation between
      nutrition, development and the severity of malignant and non-malignant
      proliferative diseases such as cancer and atherosclerosis. Therefore, the
      prevention of chronic proliferative diseases through dietary intervention is
      currently receiving considerable attention. Until now, much of the research is
      being focused on the cellular and molecular action mechanisms of dietary small
      molecules explaining their beneficial effects. Dietary chemicals may affect gene
      expression in several human diseases. However, significant progress has been made
      and several molecular action mechanisms have been proposed. Alteration of
      genetical pathways by nutrition, also called "Nutrigenomics", may offer a new
      approach for understanding the beneficial effects of dietary compounds on the
      development of severe polygenic diseases, such as cardiovascular disease,
      diabetes and hypertension. This review focuses on the nutritional genomics of
      dietary chemicals with a special emphasis on catechins. Catechins belong to the
      flavonoid family, which are polyphenolic compounds available in foods of plant
      origin. Several epidemiological studies have reported that consumption of
      flavonoids, and especially catechins might function as chemopreventive agents
      against cancer and cardiovascular diseases.

PMID- 16787200
TI  - Strategies for efficient lead structure discovery from natural products.
AB  - This investigation aims to evaluate strategies for an efficient selection of
      bioactive compounds from the multitude and biodiversity of the plant kingdom.
      Statistics prove natural products (NPs) as a source leading most consistently to
      successful development of new drugs. However, there are several reasons why the
      interest in finding bioactive NPs has generally declined at several major
      pharmaceutical companies. Their substantial argument is that the research in this
      field is time-consuming, highly complex and ineffective. A more rational and
      economic search for new lead structures from nature must therefore be a priority
      in order to overcome these problems. In this paper, different strategies are
      described to exploit the molecular diversity of bioactive secondary metabolites,
      namely classical pharmacognostic approaches and computational methods. The latter
      include various data mining tools, like virtual screening filtering experiments
      using pharmacophore models, docking studies, and neural networks, which help to
      establish a relationship between chemical structure and biological activity. The
      strengths and weaknesses of these methods will be shown in this review. Focusing
      on selected targets within the arachidonic acid cascade (phospholipase A(2), 5
      lipoxygenase, cyclooxygenase-1 and -2), several studies of successful discoveries
      in the field of anti-inflammatory NPs were scrutinized for the applied
      strategies. Both the compilation of relevant published data and recent studies
      supported by our own research clearly demonstrate the benefits of the synergistic
      effect of a hybridization of these strategies for an effective drug discovery
      from natural ingredients.

PMID- 16787201
TI  - Controlling biofilms of gram-positive pathogenic bacteria.
AB  - Many bacteria can form aggregates on interfaces, called biofilms, where they are
      much more protected against toxic agents such as antibiotics or antibodies.
      Bacteria organized in biofilms are therefore very difficult to control and often
      even high dosages of antibiotics cannot clear infectious biofilms. To form
      biofilms bacteria have to start a complex genetic program to switch from
      planktonic to sessile lifestyle. This starts with the determination of their cell
      density, a process called quorum sensing, triggered by small, water soluble
      molecules, so called autoinducers. From Gram-positive bacteria several small
      peptides are known, many of them thiolactones. More recently another group of
      compounds was discovered probably formed from ribose-homocysteine and the first
      autoinducer-II identified is a furanosyl borate diester. While small peptides are
      found to trigger the intraspecies communication autoinducer-II is assumed to be
      used for communication at the interspecies level. Taking the lead structure from
      these peptides several derivatives have been developed which prevent biofilm
      formation in many Gram-positive bacteria, including Staphylococcus aureus. Some
      of these compounds are already in clinical studies. In this review the different
      approaches to control bacterial biofilms are discussed together with the
      difficulties arising from the species-specificity of the autoinducers.

PMID- 16787202
TI  - The application of Freidinger lactams and their analogs in the design of
      conformationally constrained peptidomimetics.
AB  - Peptides exist in solution as an equilibrium mixture of conformers. The backbone
      conformational constraints are of interest as a means of limiting degrees of
      freedom and thereby constraining a synthetic peptide into the bioactive
      conformation. This concept plays an important role in the design of
      peptidomimetics in the drug development process. In the early eighties,
      Freidinger proposed the concept of protected lactam-bridged dipeptides, which was
      a milestone in the design of conformationally constrained peptides. These types
      of compounds, now widely known as Freidinger lactams, have been of interest to
      many medicinal and peptide chemists. This review seeks to present the various
      applications that Freidinger lactams and their hetero-, fused- and unsaturated
      analogs have found in the design of conformationally constrained peptidomimetics
      in different therapeutic areas.

PMID- 16787203
TI  - Natural and adaptive immune cell-based therapies in autoimmunity.
AB  - Recent studies have raised great interest in the modulation of autoimmune
      responses by manipulation of immunoregulatory cells. Several lymphocyte
      subpopulations responsible for the induction and maintenance of immune tolerance
      have been extensively studied, and much has been learned about their properties.
      Lately, a series of attempts to harness the immunoregulatory activities of these
      cells for therapeutic purposes has proven successful in preclinical studies. The
      development of new strategies for the expansion of glycolipid-induced activation
      of NKT cells and antigen-specific regulatory T cells represent examples that have
      generated considerable interest and that are leading to the development of
      immunoregulatory cell-based approaches translating the findings from the bench to
      the bedside. This review highlights the advances, obstacles and limitations of
      these studies and critically discusses the most recent findings in this rapidly
      expanding field.

PMID- 16787204
TI  - Selective alpha7 nicotinic acetylcholine receptor ligands.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand gated ion channels
      of broad distribution and structural heterogeneity. Their functional diversity
      demonstrated involvement in a variety of neuronal processes (e.g., sensory gating
      and cognitive function) and generated great interest in them as targets for
      therapeutic intervention in a number of neuropathological conditions and
      diseases. In order to control distinct nicotinic functions pharmacologically, it
      is important to design ligands that selectively interact with distinct receptor
      subtypes in such a way as to maximize the therapeutic effect and minimize the
      adverse effects. The alpha7 nAChR, a CNS subtype, has been the most intensively
      studied nAChR in recent years. Selective alpha7 nAChR agonists have been
      developed as potential candidates for the treatment of schizophrenia, cognitive
      disorders (including Alzheimer's disease), and inflammation. Despite early
      concerns that the rapid desensitization property of the alpha7 nAChR would limit
      their therapeutic potential, several have already been advanced to clinical
      trials (e.g., PH-399733, Pfizer; MEM 3454, Memory Pharmaceuticals/Roche). Further
      development of allosteric modulators and pharmaceutically relevant antagonists
      might expand the therapeutic potential of compounds that target alpha7 nAChRs. In
      this review we briefly describe the structure and function of the alpha7 nAChR
      and its in vitro and in vivo pharmacology, discuss the clinical relevance of
      these efforts, and review the current progress in alpha7 ligand development.

PMID- 16787205
TI  - Comprehensive therapy in osteoporosis using a single drug: from ADFR to strontium
      ranelate.
AB  - In vitro, strontium ranelate increases collagen and non-collagenic proteins
      synthesis by mature osteoblast enriched cells. The effects of strontium ranelate
      on bone formation were confirmed as the drug enhanced preosteoblastic cell
      replication. In the isolated rat osteoclast, a preincubation of bone slices with
      strontium ranelate induced a dose-dependent inhibition of the bone resorbing
      activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited
      preosteoclast differentiation. In a phase II dose ranging trial Strontium
      ranelate (500 mg, 1000 mg, 2000 mg/day) or placebo were given to 353
      postmenopausal women with prevalent vertebral osteoporosis. At the conclusion of
      this 2-year study, the annual increase in lumbar BMD of the group receiving 2000
      mg of strontium ranelate was + 7.3%, a significant increase in bone alkaline
      phosphatase, over a 6-month period and a significant decrease in N-telopeptide
      crosslinks throughout the 2-year period were seen. During the second year of
      treatment, the dose of 2000 mg was associated with a 44% reduction in the number
      of patients experiencing a new vertebral deformity. The primary analysis of the
      SOTI study, evaluating the effect of strontium ranelate 2000 mg on vertebral
      fracture rates, revealed a 41% reduction in the relative risk of patient
      experiencing a first new vertebral fracture with strontium ranelate throughout
      the 3-year study. The TROPOS study showed a significant reduction in the risk of
      experiencing a first non-vertebral fracture by 16% in the group treated with
      strontium ranelate throughout the 3-year study. A reduction in the risk of
      experiencing a hip fracture by 36% was also demonstrated in the patients at high
      risk of hip fracture (age > or =74 years and Femoral Neck T score < or = -2.4
      according to NHANES normative value). All these results suggest that strontium
      ranelate is a new, effective and safe treatment of vertebral and non-vertebral
      osteoporosis, with a unique mode of action.

PMID- 16787206
TI  - Design of peptide-based vaccines for cancer.
AB  - The immune system responds efficiently to bacteria, viruses and other agents
      however, the immune response to cancers is not as effective. In most cases other
      than specific genetic rearrangements leading to non-self proteins such as in
      leukemia and idiotypes in lymphoma, tumor associated proteins are self proteins
      and are not recognized by the immune system to prevent malignancy. In most
      cancers, patients develop antibodies and/or CTL-precursors to tumor associated
      antigens but are not effective in generating a therapeutic immune response.
      Adjuvants have been used with either whole tumors, subunits or peptides with the
      aim of increasing their immunity. Whole tumor antigens have certain advantages
      associated with it, such as ready availability as recombinant proteins, potential
      epitopes that can be presented by a number of MHC class I/II alleles and antibody
      development. The methods of identification of CD8 and CD4 epitopes either by use
      of epitope prediction algorithms or use of transgenic mice has made the use of
      defined synthetic peptides more attractive. The possibility to synthesize long
      peptides and introduce multiple epitopes (CD4 or CD8) from single or multiple
      antigens makes peptide a viable alternative to whole proteins. As an alternative
      to totally synthetic peptide constructs or polymers, polytopes have been
      generated by genetic engineering methods. In addition, to deliver immunogens to
      and to activate DC, receptor-mediated delivery of peptides using antibodies,
      cytokines and carbohydrates have been used. This review will encompass the
      various strategies, preclinical and clinical applications in designing peptide
      based vaccines for cancer.

PMID- 16787207
TI  - Ceramide in apoptotic signaling and anticancer therapy.
AB  - Ceramide, a product of sphingolipid metabolism, is generated in response to
      various stress stimuli, such as tumor necrosis factor-alpha, CD95/Fas,
      chemotherapeutic agents, and irradiation. Ceramide may modulate the biochemical
      and cellular processes that lead to apoptosis. However, the mechanisms by which
      ceramide regulates apoptotic events are not fully defined. It is believed that
      the biological effect of ceramide depends on its concentration, the activation or
      differentiation status of the cell, and the time frame of action. Here, we
      discuss the metabolism and cell apoptotic signaling of ceramide. The involvement
      of protein kinases (i.e. PI3K/Akt and GSK-3beta) and protein phosphatases (i.e.
      PP1 and PP2A), Bcl-2 family proteins, mitochondrial damage, and caspase cascade
      activation are demonstrated. Further, ceramide and its derivatives have recently
      been incorporated into strategies for anticancer therapies. An understanding of
      the apoptotic signaling pathways mediated by ceramide may shed light on its
      potential for therapeutic intervention.

PMID- 16787208
TI  - Macromolecular ensembles of internal and external fibrinolysis: the resources for
      enhancement of thrombolysis efficacy.
AB  - The results of the search for new plasminogen activators for thrombolytic therapy
      have been reviewed with analysis of slowdown in this process. The reserves of
      increasing the effectiveness of thrombolysis are considered and the mechanisms
      underlying the interactions between plasminogen and its activators with fibrin
      are described. The domain composition of the fibrinolytic agents and the
      functional role of their structural elements in fibrinolytic interactions are
      discussed. The action of fibrin-specific and fibrin-nonspecific plasminogen
      activators in fibrinolysis has been evaluated. The necessity of the investigation
      of the regularities of internal and external fibrinolysis has been substantiated.
      The internal fibrinolysis became the resource for enhancement of thrombolysis
      efficacy. The approaches to the use of internal fibrinolysis to increase the
      effectiveness of enzyme therapy (monotherapy with plasminogen or new-made
      plasminogen activator as well as polytherapy with combination of different
      plasminogen activators /thrombolysis trigger plus third-generation plasminogen
      activator of prolonged action/) have been outlined and the relationship between
      this research and the current tendencies in the improvement of clinical
      thrombolysis (dose reduction, adjacent therapy, etc.) has been discussed.

PMID- 16787209
TI  - Gene-gene and gene-environment interplay represent specific susceptibility for
      different types of ischaemic stroke and leukoaraiosis.
AB  - Stroke is a very frequent entity. It is the third leading cause of death and the
      leading cause of adult disability in the developed world. At a population level,
      the common sporadic form of ischaemic stroke is underpinned by both environmental
      and genetic risk factors. Typically, in clinical practice, environmental risk
      factors such as hypertension, diabetes mellitus, smoking, alcohol consumption,
      and other factors, are usually considered to be more important than genetic
      factors. However, it is the interplay of both environmental and common genetic
      factors [such as the Leiden V, methylenetetrahydrofolate reductase C677T,
      apolipopotein E 4, endothelial nitric oxide synthase G894T, angiotensin
      converting enzyme I/D and angiotensin II type 1 receptor A1166C mutations and
      polymorphisms] that leads to the development of ischaemic stroke. Indeed, a
      complex network of interactions between genetic factors and clinical risk factors
      can be supposed. This review evaluates the possible roles of gene-gene and gene
      environment interactions concerning the above genetic factors in the evolution of
      ischaemic stroke and leukoaraiosis. A knowledge of the specific genetic patterns
      which are associated with a significant risk of ischaemic stroke or leukoaraiosis
      may also draw attention to a large population at an increased risk of circulatory
      disorders. This may facilitate the choice of more effective and specific
      prevention on the basis of the genotype.

PMID- 16787210
TI  - Pharmacological treatment of atrial fibrillation: mechanisms of action and
      efficacy of class III drugs.
AB  - Atrial fibrillation represents a major clinical, social and economical matter,
      and its importance is expected to increase even more in the near future. The
      progressive ageing of population is associated with an inevitable rising in
      incidence and prevalence of this rhythm disorder, which limits functional
      capability, favours occurrence of cerebrovascular events and increases people's
      request for emergency room visits and hospital recovery. In spite of the
      increasing successes of the interventional non-pharmacological therapies, drug
      treatment of patients with atrial fibrillation in relation to conversion to sinus
      rhythm and prevention of recurrences, maintains a critical role. Several
      antiarrhythmic drugs are nowadays available, but their efficacy is limited by the
      high rate of arrhythmias recurrences and by side effects during acute and chronic
      treatment. Drugs interfering with potassium channels (Class III drugs) have been
      proposed and used in patients with atrial fibrillation. Aim of this review is to
      discuss the most recent data on the efficacy and feasibility of class III drugs
      in atrial fibrillation. Experimental and clinical data on dronedarone, ibutilide,
      dofetilide, azimilide, ersentilide and ambasilide will be hereby discussed.

PMID- 16787211
TI  - Endothelin-1: the yin and yang on vascular function.
AB  - Endothelin-1 (ET-1) is a vasoconstrictor secreted by endothelial cells, which
      acts as the natural counterpart of the vasodilator nitric oxide (NO). ET-1
      contributes to vascular tone and regulates cell proliferation through activation
      of ETA and ETB receptors. Physical factors such as shear stress, or stimuli
      including thrombin, epinephrine, angiotensin II, growth factors, cytokines and
      free radicals enhance secretion of ET-1. By contrast, mediators like nitric oxide
      (NO), cyclic GMP, atrial natriuretic peptide, and prostacyclin reduce the release
      of endogenous ET-1. Thus, under normal conditions, the effects of the ET-1 are
      carefully regulated through inhibition or stimulation of ET-1 release from
      endothelium. Endothelial dysfunction is one of the earliest landmarks of vascular
      abnormalities. Altered function of endothelium may result from absolute decrease
      in bioavailability of NO as well as from relative augment in ET-1 synthesis,
      release or activity. Imbalance in the production of vasodilator and
      vasoconstrictor agents may contribute to the onset of hemodynamic disorders.
      Since dysregulation of the endothelin system is important in the pathogenesis of
      several cardiovascular diseases, the ETA and ETB receptors are attractive
      therapeutic targets for disorders associated with elevated ET-1 levels. ET
      receptor antagonists may be regarded as disease-modifying agents thanks to their
      ability to preserve endothelial integrity when the endothelin system is
      overactive. This review summarizes the current knowledge on the role of ET-1 in
      experimental hypertension and describes recent findings on the involvement of
      MAPK signalling pathways in ET-1 release in hypertension associated with insulin
      resistance. Moreover, therapeutic applications of ET-1 receptor blockers are also
      discussed.

PMID- 16787212
TI  - Homology modeling of G-protein-coupled receptors and implications in drug design.
AB  - G-protein-coupled receptors (GPCRs) are considered therapeutically important due
      to their involvement in a variety of processes governing several cellular
      functions, and their tractability as drug targets. A large percentage of drugs on
      the market, and in development stages, target the super family of the GPCRs. The
      enormous interest in GPCR drug design is, however, limited by the scarcity of
      structural information. The only GPCR for which a three dimensional (3D)
      structure is reported is bovine rhodopsin and it belongs to class A of the GPCR
      family. As a result, there has been considerable interest in alternative
      techniques, for example, homology modeling of GPCRs, in order to derive useful
      three dimensional models of other proteins for use in structure-based drug
      design. However, homology modeling of GPCRs is not straightforward, and
      encounters several problems, owing to the availability of a single structural
      template, as well as the low degree of sequence homology between the template and
      target sequences. There are several key issues which need to be considered during
      every stage of GPCR homology modeling, in order to derive reasonable 3D models.
      Homology modeling of GPCRs has been utilized increasingly in the past few years
      and has been successful, not only in furthering the understanding of ligand
      protein interactions, but also in the identification of new and potent ligands.
      Thus, with the lessons learned from past experiences and new developments,
      homology modeling in case of GPCRs can be harnessed for developing more reliable
      three dimensional models. This, in turn, will provide better tools to use in
      structure-based drug design leading to the identification of novel and potent
      GPCR ligands for several therapeutic indications.

PMID- 16787213
TI  - Insights into mechanism of NMD: digging from the NMD-related protein complexes.
AB  - Nonsense-mediated RNA decay (NMD), an mRNA quality control mechanism, triggers
      degradation of mRNAs that contain premature termination codon (PTC) within their
      coding regions. NMD is a relatively conservative process that involves many trans
      acting factors. The key domains for their function in NMD are conserved in
      evolution. These trans-acting factors are classified as different groups by their
      function in NMD. In addition, the mRNP formation is dynamic in NMD process
      because of sequential recruitment and interaction of these factors. To gain an
      insight into the mechanism of NMD, we dissect the mechanism of NMD based on the
      information on the structure, the regulation and interaction of these factors.

PMID- 16787214
TI  - A review of current knowledge of the complement system and the therapeutic
      opportunities in inflammatory arthritis.
AB  - The complement activation system, a key component of the innate immune system,
      protects the host from microorganisms such as bacteria, and other foreign threats
      including abnormal cells. However, it is also double-edged in that it can have
      negative effects in the host; excessive complement activation damages the host
      and can even kill in anaphylactic shock and septic shock. Regulation of the
      complement system is a useful strategy to control inflammatory diseases,
      including inflammatory arthritis. Rheumatoid arthritis is a common inflammatory
      disease worldwide. Many medicines are developed to control inflammation,
      including recently developed biological response modifiers such as anti-TNF and
      IL-6 agents. Nevertheless, in some patients disease remains difficult to control
      because of complications, side effects and tolerance of medicines. In
      inflammatory arthritis, including rheumatoid arthritis, there is abundant
      evidence implicating complement activation in humans and animal models.
      Therefore, anti-complement agents might be beneficial as part of clinical
      treatment. However, at present, there are still no applicable agents for
      therapeutic regulation of excessive complement activation in chronic disease.
      Novel agents in development might be useful as a strategy to control complement
      activation. Here I describe recent knowledge of the complement system in
      inflammatory arthritis, the recent developments in anti-complement agents and
      their considerable potential for the future.

PMID- 16787215
TI  - Killing time for cancer stem cells (CSC): discovery and development of selective
      CSC inhibitors.
AB  - Can cancer be cured or will it have to be controlled as a chronic disease?
      Despite a better understanding of the biology of tumour cells, the treatment of
      most cancers has not significantly changed for the past three decades. Are
      current cancer drugs targeted at the wrong kind of cells? Accumulating evidence
      has implicated that cancer is a disease of stem cells. In this context, a small
      fraction of cancer cells adopt the properties of stem cells. In some cases, the
      cancer stem cells (CSC) could be the close derivative of normal tissue stem
      cells. In either situation, the net result will be the same, in that CSC are the
      cells to be used as targets in the development of molecular and pharmaceutical
      therapies to treat and prevent human cancer. This could be a paradigm shift in
      the treatment of cancer, away from targeting the blast cells and towards the
      targeting of the CSC. A challenge to this approach will be to find a way to
      specifically target CSC without toxicity to normal cells. In this article, we
      propose how CSC can be used in therapy programs (target identification, drug
      discovery, etc.). Therefore, in the future, it might be possible to rid a patient
      of all his/her cancer cells, including the cancer stem cells.

PMID- 16787216
TI  - Emerging role of intravascular ultrasound in the assessment of experimental anti
      atherosclerotic therapies.
AB  - Intravascular ultrasound (IVUS) imaging within the coronary arteries has emerged
      as the gold standard for the quantitation of the extent of atherosclerosis
      plaque. Studies that have utilized IVUS have enhanced our understanding of the in
      vivo natural history of atherogenesis. As IVUS can be performed within the same
      coronary artery at different time points it has become an attractive tool for the
      assessment of the effect of experimental anti-atherosclerotic strategies on
      plaque burden. This review will review the evolution of IVUS as an imaging
      modality and highlight its use to assess a number of interventions that are
      directed at both modification of existing risk factors and novel targets that are
      thought to play a pivotal role in the pathogenesis of atheroma formation.

PMID- 16787217
TI  - Bringing kinases into focus: efficient drug design through the use of
      chemogenomic toolkits.
AB  - The study of protein target families, as opposed to single targets, has become a
      very powerful tool in chemogenomics-led drug discovery. By integrating
      comprehensive chemoinformatics and bioinformatics databases with customised
      analytical tools, a 'Toolkit' approach for the target family is possible, thus
      allowing predictions of the ligand class, affinity, selectivity and likely off
      target issues to be made for the guidance of the medicinal chemist. In this
      review, we highlight the development and application of the Toolkit approach to
      the protein kinase superfamily, drawing on examples from lead optimisation
      studies and the design of focused libraries for lead discovery.

PMID- 16787218
TI  - Antiviral and immunomodulatory properties of new pro-glutathione (GSH) molecules.
AB  - Reduced glutathione (GSH) is present in millimolar concentrations in mammalian
      cells. It is involved in many cellular functions such as detoxification, amino
      acid transport, production of coenzymes, and the recycling of vitamins E and C.
      GSH acts as a redox buffer to preserve the reduced intracellular environment.
      Decreased glutathione levels have been found in numerous diseases such as cancer,
      viral infections, and immune dysfunctions. Many antioxidant molecules, such as
      GSH and N-acetylcysteine (NAC), have been demonstrated to inhibit in vitro and in
      vivo viral replication through different mechanisms of action. Accumulating
      evidence suggests that intracellular GSH levels in antigen-presenting cells such
      as macrophages, influence the Th1/Th2 cytokine response pattern, and more
      precisely, GSH depletion inhibits Th1-associated cytokine production and/or
      favours Th2 associated responses. It is known that GSH is not transported to most
      cells and tissues in a free form. Therefore, a number of different approaches
      have been developed in the last years to circumvent this problem. This review
      discusses the capacity of some new molecules with potent pro-GSH effects either
      to exert significant antiviral activity or to augment GSH intracellular content
      in macrophages to generate and maintain the appropriate Th1/Th2 balance. The
      observations reported herein show that pro-GSH molecules represent new
      therapeutic agents to treat antiviral infections and Th2-mediated diseases such
      as allergic disorders and AIDS.

PMID- 16787219
TI  - Delivering drugs to the central nervous system: a medicinal chemistry or a
      pharmaceutical technology issue?
AB  - This review aims to summarize the non-invasive approaches employed in delivering
      drugs to the central nervous system which is severely hindered by the presence of
      the blood-brain barrier (BBB) that limits molecular permeation. Particular
      attention will be placed on the several available strategies for delivering drugs
      into the brain, through circumvention of the BBB, in order to critically address
      the medicinal chemistry and the pharmaceutical technology contributions.

PMID- 16787221
TI  - Carbon nanotubes: materials for medicinal chemistry and biotechnological
      applications.
AB  - Carbon nanotubes are considered as molecular wires exhibiting novel properties
      for diverse applications including medicinal and biotechnological purposes.
      Surface chemistry on carbon nanotubes results on their solubilization in organic
      solvents and/or aqueous/physiological media. Herein, we will present how
      interfacing such novel carbon-based nanomaterials with biological systems may
      lead to new applications in diagnostics, vaccine and drug delivery. Recent
      developments in this rapidly growing field will be presented thus suggesting
      exciting opportunities for the utilization of carbon nanotubes as useful tools
      for biotechnological applications. Emphasis will be placed in the integration of
      biomaterials with carbon nanotubes, which enables the use of such hybrid systems
      as biosensor devices, immunosensors and DNA-sensors.

PMID- 16787220
TI  - Novel therapeutics for diabetic micro- and macrovascular complications.
AB  - Diabetic patients have a two- to four-fold increased risk for the development of
      microvascular (renal, neuronal and retinal) and macrovascular complications.
      Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic
      patients even with careful glycaemic, blood pressure and lipid control. With the
      worldwide increase in the incidence diabetes, new strategies to prevent the
      complications are urgently needed. Mediators of vascular damage of diabetes
      include poor glycemic control, lipoprotein abnormalities, hypertension, oxidative
      stress, inflammation and advanced glycation end-products (AGEs), which are
      modified proteins formed by non-enzymatic glycation. AGEs are resistant to
      enzymatic degradation and therefore very stable, thus their accumulation
      continues throughout aging. AGE accumulation causes arterial stiffening in the
      vessel wall, glomerulosclerosis in the kidney, and vascular hyperpermeability in
      the retina. Through their interaction with their putative receptor the so-called
      receptor for AGEs (RAGE), AGEs activate endothelial cells and macrophages,
      generate reactive oxygen species (ROS), induce overexpression of vascular
      endothelial growth factor (VEGF) and vascular cell adhesion molecule-1 (VCAM-1),
      and quench nitric oxide (NO). The pharmacological treatment currently available
      for either Type 1 or Type 2 diabetic patients does not directly address the
      excess accumulation of AGEs. Novel compounds that inhibit AGE formation, cleave
      AGE cross-links or reverse their interaction with RAGE are now accessible and
      could prove useful in meeting this challenge. Other strategies such as inhibition
      of the hexosamine pathway, vitamin therapy to reduce oxidation and AGE
      accumulation, reduction of the ROS, or blocking the actions of growth factors or
      intracellular messengers of cell differentiation are also currently under
      research. This review will recount recent advances in the development of
      therapeutic approaches for inhibiting and treating the development of diabetic
      end-organ damage.

PMID- 16787222
TI  - Therapeutic applications of glycosaminoglycans.
AB  - Complex polysaccharides, hyaluronic acid or hyaluronan (HA), keratan sulfate
      (KS), chondroitin sulfates (CSs) and heparin (Hep)/heparan sulfate (HS), are a
      class of ubiquitous molecules exhibiting a wide range of biological functions.
      They are widely distributed as glycosaminoglycans (GAGs) sidechains of
      proteoglycans (PGs) in the extracellular matrix and at cellular level. The recent
      emergence of improved enzymatic and analytical tools for the study of these
      complex sugars has produced a virtual explosion in the field of glycomics. In
      particular, the study of the GAG family of polysaccharides has shed considerable
      light on the way in which specific carbohydrate structures modulate cellular
      phenotypes. In addition to the well-known therapeutic applications of some of
      these macromolecules, such as HA and derivatives as structure modifying molecules
      and possessing gel-like properties able to provide functional support for
      tissues, Hep as an anticoagulant and antithrombotic drug and CS in the treatment
      of osteoarthritis (OA), this increased understanding of GAG structure-function
      relationship has led to the discovery of novel pharmaceuticals for the possible
      treatment of serious diseases, such as cancer. In this paper, the structure and
      the therapeutic applications of several complex natural polysaccharides,
      including HA, CS/DS, Hep and their derivatives, are presented and discussed also
      in the light of the many questions still left unanswered, such as improved
      preparation and GAG-based drugs with improved properties and new possible
      therapeutic applications.

PMID- 16787223
TI  - Development of BACE1 inhibitors for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most
      common cause of dementia. The production and accumulation of beta-amyloid
      peptides (Abeta) from the beta-amyloid precursor protein (APP) are believed to
      play a key role in the onset and progression of AD. BACE1 (beta-site APP cleaving
      enzyme 1) is the protease responsible for the N-terminal cleavage of APP leading
      to the production of Abeta peptides and the development of BACE1 inhibitors as
      potential therapeutic agents for AD has generated tremendous interests from both
      academia and the pharmaceutical industry. A wide variety of BACE1 inhibitors have
      been reported, several of which have demonstrated highly promising efficacy in
      animal models of AD. This review focuses on recent disclosures of BACE1
      inhibitors in the patent and scientific literature, covering the period from
      approximately May 2004 to November 2005.

PMID- 16787224
TI  - Clinical proteomics: new trends for protein microarrays.
AB  - Protein microarrays are an emerging class of nanotechnology for tracking many
      different proteins simultaneously. Much progress has been made for applications
      in basic sciences. Translation of these methods for the treatment of patients,
      however, is slow, because the realities in the clinic are rarely taken into
      account, and proteomic changes in cultured cell lines might not fully reflect
      human diseases due to the lack of the tissue microenvironment. In this review, we
      summarise current protein microarray approaches that are being developed for
      profiling tissues and histopathologically defined cell populations from cancer
      patients. We provide an overview of clinical applications for protein lysate
      microarrays and discuss the power of this technology for the discovery of disease
      markers for cancer diagnosis and individualised treatment.

PMID- 16787225
TI  - Small molecule glucokinase activators as glucose lowering agents: a new paradigm
      for diabetes therapy.
AB  - Glucokinase (GK) is a molecular sensor that regulates glucose induced insulin
      secretion in pancreatic beta-cells and glucose homeostasis in the liver via
      catalysis of glucose to glucose-6-phosphate. The recent discovery and development
      of small molecule glucokinase activators represents a potentially important
      development for the management of type 2 diabetes. Since the discovery of the
      first orally active small molecule GK activator RO0281675, a number of research
      groups have reported the identification of potent activators. In this review, the
      biological significance of GK in whole body glucose homeostasis is briefly
      described coupled with the recent progress regarding the identification of novel
      small molecule GK activators.

PMID- 16787226
TI  - G protein-coupled receptors in regulation of body weight.
AB  - In this issue of CNS & Neurological Disorders-Drug Targets, we focus on G protein
      coupled receptors (GPCRs) that are involved in regulating body weight. In six
      reviews, the melanocortins system (including MC4 and MC3 receptors, Agrp, MSH),
      the NPY receptors (including NPY-Y1, NPY-Y2, and NPY-Y5, PYY3-36), the
      cannabinoid system (including the development of rimonabant), the ghrelin (GHS,
      growth hormone secretagogue) system, the monoamine GPCRs (including serotonin,
      adrenergic and histamine receptors), orexin (hypocretin) system and the galanin
      receptors are covered. In this overview, an introduction to the GPCRs and the
      field of central regulation of food intake is provided together with brief
      mentioning of some other GPCRs that are also implicated in regulation of body
      weight, such as the melanin-concentrating hormone (MCH), neuromedin U, prolactin
      releasing peptide (PrRP), bombesin, cholecystokinin (CCK), Glucagon-like peptide
      1 (GLP-1) (and oxyntomodulin), neuropeptide B (NPB) and neuropeptide W (NPW),
      opioids peptides, free fatty acid (FFA) receptors (GPR40, GPR41). In total over
      40 GPCRs are listed that have been implicated to affect regulation of body
      weight.

PMID- 16787227
TI  - Melanocortin receptors as drug targets for disorders of energy balance.
AB  - There is overwhelming evidence that the brain melanocortin system is a key
      regulator of energy balance, and dysregulations in the brain melanocortin system
      can lead to obesity. The melanocortin system is one of the major downstream
      leptin signaling pathways in the brain. In contrast to leptin, preclinical
      studies indicate that diet-induced obese animals are still responsive to the
      anorectic effects of melanocortin receptor agonists, suggesting the melanocortin
      system is an interesting therapeutic opportunity. Besides regulating energy
      balance, melanocortins are involved in a variety of other neuroendocrine
      processes, including inflammation, blood pressure regulation, addictive and
      sexual behavior, and sensation of pain. This review evaluates the melanocortin
      system function from the perspective to use specific melanocortin (MC) receptors
      as drug targets, with a focus on the treatment of obesity and eating disorders in
      humans, and the implications this may have on mechanisms beyond the control of
      energy balance.

PMID- 16787228
TI  - NPY receptors as drug targets for the central regulation of body weight.
AB  - Neuropeptide Y (NPY) is present in the hypothalamus, where it is believed to play
      a key role in the control of food intake. Evidence for this assertion has come
      from studies demonstrating that acute administration of NPY into the hypothalamus
      or into the brain ventricles leads to increased food intake. In the case of
      chronic administration, the hyperphagic effects of NPY are prolonged leading to
      the development of an obese state. NPY levels in the hypothalamus are temporally
      correlated with food intake and are markedly elevated in response to energy
      depletion. However, attempts to demonstrate an important role for NPY in the
      control of food intake using NPY knockout mice, NPY antisense
      oligodeoxynucleotides and anti-NPY antibodies has produced equivocal results.
      Despite this many pharmaceutical companies have moved ahead with the search for
      agonists and antagonists of NPY receptor subtypes as anti-obesity agents.
      Antagonists of the NPY Y(1) and NPY Y(5) receptor subtype initially looked
      promising since analogs of NPY with high selectivity for these receptors strongly
      stimulated food intake. However, attempts to inhibit the signaling of NPY through
      the NPY Y(1) and NPY Y(5) receptors has produced equivocal effects on food
      intake. Recent observations that the gut derived peptide PYY(3-36) suppresses
      appetite by stimulating both peripherally and centrally located NPY Y(2)
      receptors remain controversial in animals but the effects look promising in human
      studies. Whether this will be the long awaited therapy based on manipulation of
      NPY receptors will await further studies of long term efficacy and more
      importantly a favorable side effect profile.

PMID- 16787229
TI  - Endocannabinoids in appetite control and the treatment of obesity.
AB  - Research into the endocannabinoid 'system' has grown exponentially in recent
      years, with the discovery of cannabinoid receptors and their endogenous ligands,
      such as anandamide and 2-arachidonoylglycerol (2-AG). Important advances have
      been made in our understanding of endocannabinoid transduction mechanisms, their
      metabolic pathways, and of the biological processes in which they are implicated.
      A decade of endocannabinoid studies has promoted new insights into neural
      regulation and mammalian physiology that are as revolutionary as those arising
      from the discovery of the endogenous opioid peptides in the 1970s. Thus,
      endocannabinoids have been found to act as retrograde signals: released by
      postsynaptic neurons, they bind to presynaptic heteroceptors to modulate the
      release of inhibitory and excitatory neurotransmitters through multiple G-protein
      coupled receptor (GPCR)-linked effector mechanisms. The metabolic pathways of
      anandamide and 2-AG have now been been characterised in great detail, and we can
      anticipate that these pathways -- together with endocannabinoid uptake mechanisms
      -- will complement cannabinoid receptors as targets for the pharmacological
      analysis of the physiological functions of these substances. Specific insights
      into the potential role of endocannabinoid-CB1 receptor systems in central
      appetite control, peripheral metabolism and body weight regulation herald the
      clinical application of CB1 receptor antagonists in the management of obesity and
      its associated disorders.

PMID- 16787230
TI  - Monoamine receptors in the regulation of feeding behaviour and energy balance.
AB  - We evaluate the likely utility of drugs that interact, either directly or
      indirectly, with monoamine binding receptors for the treatment of obesity. We
      discuss ligands at dopaminergic, adrenergic, serotoninergic and histaminergic
      receptors and also drugs that either release or inhibit the reuptake of monoamine
      neurotransmitters. We review evidence from preclinical studies of receptor
      distribution and function, together with the consequences of gene deletion in
      transgenic mouse strains and the results from human studies where these are
      available. In addition we consider the side effect profiles that would be
      expected of these potential anti-obesity treatments. We conclude that compounds
      interacting with 5-HT(2C), 5-HT(6) and histamine H(3) receptors may be of
      particular interest as specific drug development targets for the treatment of
      appetite disturbance in obesity.

PMID- 16787231
TI  - Roles of orexins and orexin receptors in central regulation of feeding behavior
      and energy homeostasis.
AB  - Orexins were initially recognized as regulators of feeding behavior due to their
      exclusively production in the lateral hypothalamic area (LHA), a feeding center.
      Subsequently, the finding that orexin deficiency causes narcolepsy in humans and
      animals suggested that these hypothalamic neuropeptides play a critical role in
      regulating and maintaining sleep/wakefulness states. Proper maintenance of
      arousal during food searching and intake is essential for an animal's survival.
      Therefore, feeding behavior and sleep/wakefulness states are appropriately
      coordinated. For example, when faced with reduced food availability, animals
      adapt with a longer wakefulness period, which disrupts the normal circadian
      pattern of activity. The discovery that orexin neurons are regulated by
      peripheral metabolic cues, including ghrelin, leptin and glucose, suggests that
      they might have important roles as a link between energy homeostasis and
      sleep/wakefulness states. Recent studies on afferent (input) systems of orexin
      neurons further suggest roles of orexin and orexin receptors in the coordination
      of feeding, arousal and emotion.

PMID- 16787232
TI  - Galanin/GALP receptors and CNS homeostatic processes.
AB  - Galanin is a 29/30 amino acid peptide neurotransmitter that is widely distributed
      throughout the central nervous system and periphery. There are three well
      characterized G-protein coupled galanin receptors subtypes (GalR1-3). A more
      recently discovered 60 amino acid galanin-like peptide (GALP) shares amino acid
      sequence homology with galanin (1-13) in position 9-21 and has high binding
      affinity for GalR1-3, with highest affinity for GalR3. Considerable evidence has
      accumulated that implicates both galanin and GALP as playing important roles in
      regulating food and water intake behavior and related neuroendocrine functions.
      Pharmacological tools are emerging that will allow dissociation of specific roles
      for the peptides and their associated receptor subtypes in mediating the
      homeostatic processes of energy and fluid balance.

PMID- 16787233
TI  - D1 and functionally selective dopamine agonists as neuroprotective agents in
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder that results
      in major motor disturbances due primarily to loss of midbrain dopamine neurons.
      The mainstream treatment has been dopaminergic replacement therapy aimed at
      symptomatic relief, with the gold standard drug being the dopamine precursor
      levodopa. The general dogma has been that levodopa works primarily by indirectly
      activating the D(2) family of dopamine receptors. Recently, a number of direct
      dopamine agonists that target the D(2) and D(3) dopamine receptors have been used
      as dopaminergic replacement strategies. Although these direct D(2) and D(3) drugs
      cause only modest improvement in motor function compared to levodopa, they can
      delay the initiation of levodopa and can act synergistically with levodopa. In
      addition, they can delay the onset of levodopa-related motor complications.
      Recent imaging data also suggest that they may have neuroprotective effects.
      Whereas D(2)/D(3) agonists have received much attention as several drugs are
      available for clinical trials and usage, there has been a large body of data
      showing that the D(1) receptor actually may play a larger role in restoration of
      normal motor function. This review examines the current use of dopamine D(2)/D(3)
      agonists in treatment of PD and their potential for providing neuroprotection.
      Furthermore, we also examine the potential that D(1) agonists might have in
      neuroprotective actions in the disease progression.

PMID- 16787234
TI  - Growth hormone secretagogue (ghrelin-) receptors--a complex drug target for the
      regulation of body weight.
AB  - The growth hormone secretagogue receptor (GHS-R) is expressed in several tissues
      and seems to mediate the different actions of the synthetic growth hormone
      secretagogues (GHS) and the endogenous ligand of this receptor, ghrelin. The GHS
      R belongs to the family of G-protein coupled receptors (GPCR). Two different
      receptor variants, type 1a and 1b, have been described and they seem to mediate
      different actions in different tissues. In addition to their functions on growth
      hormone (GH) secretion and food intake, ghrelin and its receptor are involved in
      several cardiovascular mechanisms, pancreatic functions, adipogenesis, gonadal
      function, immune system actions or tumoral cells. This review will summarize data
      regarding the structure of the GHS-R gene, reports investigating the expression,
      control and functions of the GHS-R in various tissues, and studies of the
      underlying transcriptional mechanisms and the genetic manipulation of both
      ghrelin and GHS-R. Thus, it seems clear the possibility that ghrelin and/or GHS
      analogs, acting as either agonists or antagonists on different activities, might
      have clinical impact.

PMID- 16787235
TI  - Signaling mechanisms underlying Abeta toxicity: potential therapeutic targets for
      Alzheimer's disease.
AB  - The accumulation of amyloid beta peptide (Abeta) is believed to be an early and
      critical event leading to synapse and neuronal cell loss in Alzheimer's Disease
      (AD). Abeta itself is toxic to neurons in vitro and the load of Abeta in vivo
      causes the loss of synapses and neurons in brain in animal models. Therefore,
      there has been considerable interest in elucidating the mechanism(s) of Abeta
      neurotoxicity. Here, we review the molecular signaling pathways involved in Abeta
      induced cell death, including signaling through the neuronal nicotinic receptor
      and the Abeta-triggered generation of reactive oxygen species (ROS) leading to
      the activation of the c-jun N-terminal kinase (JNK), and the ensuing
      phosphorylation of p66Shc and inactivation of the Forkhead transcription factors.
      This focused review not only provides a better understanding of the signaling
      mechanisms involved in Abeta-induced cell death, but also underscores the
      potential of JNK, p66Shc, Forkhead proteins, p25/cdk5, and neuronal nicotinic
      receptor, as therapeutic targets for AD.

PMID- 16787236
TI  - The vitamin D neuroendocrine system as a target for novel neurotropic drugs.
AB  - Vitamin D is a seco-steroid hormone with multiple functions in the nervous
      system. Physiological brain mechanisms of vitamin D and its receptors include
      neuroprotection, antiepileptic effects, immunomodulation, possible interplay with
      several brain neurotransmitter systems and hormones, as well as the regulation of
      behaviours. Here we review the important role of the vitamin D neuroendocrine
      system in the brain, and outline perspectives for the search for novel
      neurotropic drugs to treat various vitamin D-related dysfunctions.

PMID- 16787239
TI  - Iron chelation as therapy for HIV and Mycobacterium tuberculosis co-infection
      under conditions of iron overload.
AB  - Iron chelators, as treatment for conditions of iron overload, have implications
      for AIDS and tuberculosis (TB) since excess iron in the system assists HIV and
      Mycobacterium tuberculosis (M.tb) multiplication. Excess iron, especially due to
      dietary habits, is almost as common in sub-Saharan Africa as infections by the
      two organisms. That HIV and M.tb influence each other's replication during co
      infection is well established, but in vitro evaluations of concurrent infection
      of the two under conditions of iron overload and determining whether chelators
      reverse the effect, are limited. This review provides brief commentary on the
      possibility of iron chelators presently in clinical use influencing simultaneous
      HIV-M.tb infections during iron loading and the feasibility of evaluating this in
      vitro.

PMID- 16787241
TI  - Cellular entry of HIV: Evaluation of therapeutic targets.
AB  - In the absence of a vaccine which could stop the HIV/AIDS pandemic, the
      development of therapeutic options is of utmost interest. The combined use of
      inhibitors of reverse transcriptase and protease as highly active antiretroviral
      therapy (HAART) provided the first effective treatment of HIV/AIDS and
      significantly decreased the number of AIDS related deaths in industrialized
      countries. However, the emergence of resistant viruses and the toxic side effects
      of HAART highlights that novel therapies are urgently required. The inhibition of
      HIV-1 entry is a promising option. Entry of HIV-1 into target cells involves
      interactions of the viral envelope protein (Env) with CD4 and a coreceptor,
      usually CCR5 or CXCR4. Env binding to receptor triggers several conformational
      rearrangements in Env, which involve the creation and/or exposure of structural
      intermediates pivotal to fusion of the viral and cellular membranes. Both,
      cellular receptors and structures in Env associated with membrane fusion are
      targets for therapeutic intervention. Here, we will discuss how HIV-1 enters
      cells and introduce strategies how this process can be inhibited.

PMID- 16787240
TI  - Potential use of pharmacological cyclin-dependent kinase inhibitors as anti-HIV
      therapeutics.
AB  - Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA
      polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are
      currently in clinical trials as potential cancer therapeutics since CDK
      hyperactivation is detected in the majority of neoplasias. Within the last few
      years, the anti-viral effects of PCIs have also been observed against various
      viruses, including human immunodeficiency virus (HIV), herpes simplex virus, and
      murine leukemia virus. Through the inhibition of CDK2 and 9, the cellular co
      factors for HIV-1 Tat transactivation, HIV-1 replication is blocked by two
      specific PCIs, CYC202 and flavopiridol, respectively. In this article, we will
      review the inhibitory mechanisms of flavopiridol and CYC202 and discuss their
      possible usage in AIDS treatment.

PMID- 16787242
TI  - Chromatin modifications (acetylation/ deacetylation/ methylation) as new targets
      for HIV therapy.
AB  - Human immunodeficiency virus (HIV) is one of the most deadly threats to the human
      race. Though the developed countries have been able to control the epidemic by
      utilizing the discovery of very expensive diagnostics, the situation is
      dangerously alarming in developing and underdeveloped countries. However,
      development of highly active anti- retroviral drugs has improved the survival and
      quality of life, but prolonged treatment results in viral load rebound to
      pretherapy levels. Recent advances in our understanding of eukaryotic and genome-
      integrated viral gene expression showed that regulation of chromatin function is
      closely linked to the multiplication of HIV. Therefore, a new therapeutic
      approach has been initiated targeting the chromatin-modifying enzymes mainly
      histone acetyltransferases and deacetylases which may lead to a better and
      economical anti- HIV combinatorial therapeutics. In this review, we have
      discussed the mechanisms of HIV gene expression in the chromatin context and its
      potentiality to be exploited as new therapeutic target.

PMID- 16787243
TI  - Recent developments in delivery of nucleic acid-based antiviral agents.
AB  - Rapid advances in viral genomics, gene function and regulation, as well as in
      rational drug design, have led to the development of gene-based drugs that can
      induce protective antiviral immunity, interfere with viral replication, suppress
      viral gene expression or cleave viral mRNAs. Several such drug candidates have
      been developed in recent years against various viruses including HIV. Although
      gene-based agents show promise as anti-viral agents their therapeutic efficacy
      may be restricted by limited delivery to intracellular sites of viral replication
      and in vivo nuclease degradation. Enhancement of the efficacy of gene-based drugs
      by encapsulation within liposomes or insertion within viral vectors has been
      evaluated. This review will highlight recent developments in delivery systems
      used to target nucleic acid-based drugs into sites of viral replication,
      therefore avoiding potential drug toxicity in non-viral infected organs. Liposome
      encapsulation and insertion of nucleic acid-based drugs within viral vectors can
      significantly enhance antiviral efficacies. Viral vector-mediated therapy usually
      results in greater expression of the gene-based drug than with liposome delivery,
      however significant safety concerns have been raised in regards to viral vector
      therapies. Research is ongoing to increase drug delivery to the desired target
      cells while eliminating adverse side effects.

PMID- 16787244
TI  - Recombinant human polyclonal antibodies: A new class of therapeutic antibodies
      against viral infections.
AB  - The mammalian immune system eliminates pathogens by generating a specific
      antibody response. Polyclonality is a key feature of this immune response: the
      immune system produces antibodies which bind to different structures on a given
      pathogen thereby increasing the likelihood of its elimination. The vast majority
      of current recombinant antibody drugs rely on monospecific monoclonal antibodies.
      Inherently, such antibodies do not represent the benefits of polyclonality
      utilized by a natural immune system and this has impeded the identification of
      efficacious antibody drugs against infectious agents, including viruses. The
      development of novel technologies has allowed the identification and
      manufacturing of antigen-specific recombinant polyclonal human antibodies, so
      called symphobodies. This review describes the rationale for designing drugs
      based on symphobodies against pathogenic viruses, including HIV, vaccinia and
      smallpox virus, and respiratory syncytial virus.

PMID- 16787245
TI  - Therapeutic AIDS vaccines.
AB  - Therapeutic HIV vaccines represent promising strategy as an adjunct or
      alternative to current antiretroviral treatment options for HIV. Unlike
      prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic
      vaccines are given to already infected individuals to help fight the disease by
      modulating their immune response. The first immunotherapeutic trial in AIDS
      patients was conducted in 1983. Since then several dozen conventional therapeutic
      vaccine trials have been carried out. Unfortunately, the results have
      consistently shown that while HIV-specific immune responses were evident as a
      result of vaccination, the clinical improvement has been seldom observed. The
      instances of the apparent clinical benefit were invariably associated with
      unconventional vaccines that acted in accord with the principles of
      alloimmunization and/or autologous vaccination. All such vaccines were derived
      from the blood of HIV carriers or a cell culture and thus they inherently
      contained allo- or self-antigens unrelated to HIV. This intriguing observation
      raises the issue whether this clinically successful approach has been unduly
      neglected. The current strategy biased toward vaccines, which have shown little
      evidence of clinical efficacy, needs to be diversified and supplemented with
      research on alternative vaccine approaches geared toward immune tolerance
      induction.

PMID- 16787246
TI  - Anti-HIV therapy: Current and future directions.
AB  - Although combinations of drugs that target the HIV reverse transcriptase and
      protease enzymes have clearly revolutionized the treatment of HIV/AIDS, problems
      with these agents, such as viral escape mutants, persistence of viral reservoirs,
      poor patient compliance due to complicated regimens, and toxic side effects, have
      emphasized the need for development of new drugs with novel mechanisms of action,
      as well as an HIV vaccine. Recently two new classes of drugs have been identified
      that interfere with the membrane fusion reaction required for HIV entry of target
      cells. Two such agents, T-20 (enfuvirtide) and T-1249, which have been approved
      by the Food and Drug Administration (FDA), block the action of the fusogenic
      envelope glycoprotein gp41. Others target the HIV coreceptors CCR5 and CXCR4, and
      are now in clinical trials. Also under development are novel agents that target
      the HIV integrase and HIV regulatory gene products as well as immunomodulators
      such as IL-12 and IL-2. This article will focus on these and other novel
      approaches to HIV therapeutics.

PMID- 16787247
TI  - Effects of ACE inhibitors on skeletal muscle.
AB  - Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity, mortality,
      hospital admissions, and decline in physical function and exercise capacity in
      congestive heart failure (CHF) patients. These therapeutic effects are attributed
      primarily to beneficial cardiovascular actions of these drugs. However, it has
      been suggested that ACE inhibitor-induced positive effects may also be mediated
      by direct action on the skeletal muscle. In particular, two recently published
      observational studies documented that among hypertensive subjects free of CHF,
      treatment with ACE inhibitors was associated with better performance and muscular
      outcomes and genetic studies also support the hypothesis that the ACE system may
      be involved in physical performance and skeletal muscle function. Effects on the
      skeletal muscle are probably mediated by mechanical, metabolic, anti
      inflammatory, nutritional, neurological and angiogenetic actions of these drugs.
      These studies may have major public health implications for older adults, as
      consequence of the fact that, in this population, gradual loss of muscle mass and
      muscle strength can play a key role in the onset and progression of disability.
      Therefore, if findings of observational studies will be later confirmed in
      randomized controlled trials, ACE inhibitors could represent an effective
      intervention to prevent physical decline in the elderly, leading to greater
      autonomy in this growing population.

PMID- 16787249
TI  - The role of T-type calcium channels in epilepsy and pain.
AB  - T-type calcium channels open in response to small depolarizations of the plasma
      membrane. The entry of two positive charges with every calcium ion leads to a
      further depolarization of the membrane, the low threshold spike, and opening of
      channels that have a higher threshold. In this manner, T-channels play an
      important pacemaker role in gating the activity of Na+ and Ca2+ channels. T
      channels are preferentially expressed in dendrites, suggesting they play
      important roles in synaptic integration. Pharmacological evidence indicates that
      they are expressed in the receptive fields of sensory neurons, suggesting they
      play a primary role in nociception. Molecular cloning of the three T-channel
      genes has allowed detailed studies on their channel properties, pharmacology,
      distribution in the brain, up-regulation in animal models of disease, and
      provided the tools to screen for novel drugs. Studies on transgenic animals have
      provided the proof-of-concept that T-channels are important drug targets for the
      treatment of absence epilepsy and neuropathic pain. Mutations in ion channel
      genes, or channelopathies, have been found in many diseases. Similarly, T-channel
      gene mutations have been found in patients with childhood absence epilepsy.
      Considering the important role T-channels play in the thalamus, it is likely that
      T-channel mutations also contribute to a wider range of disorders characterized
      by thalamocortical dysrhythmia.

PMID- 16787250
TI  - K+ channel blockers: novel tools to inhibit T cell activation leading to specific
      immunosuppression.
AB  - During the last two decades since the identification and characterization of T
      cell potassium channels great advances have been made in the understanding of the
      role of these channels in T cell functions, especially in antigen-induced
      activation. Their limited tissue distribution and the recent discovery that
      different T cell subtypes carrying out distinct immune functions show specific
      expression levels of these channels have made T cell potassium channels
      attractive targets for immunomodulatory drugs. Many toxins of various animal
      species and a structurally diverse array of small molecules inhibiting these
      channels with varying affinity and selectivity were found and their successful
      use in immunosuppression in vivo was also demonstrated. Better understanding of
      the topological differences between potassium channel pores, detailed knowledge
      of toxin and small-molecule structures and the identification of the binding
      sites of blocking compounds make it possible to improve the selectivity and
      affinity of the lead compounds by introducing modifications based on structural
      information. In this review the basic properties and physiological roles of the
      voltage-gated Kv1.3 and the Ca2+-activated IKCa1 potassium channels are discussed
      along with an overview of compounds inhibiting these channels and approaches
      aiming at producing more efficient modulators of immune functions for the
      treatment of diseases like sclerosis multiplex and type I diabetes.

PMID- 16787251
TI  - The renal epithelial sodium channel: genetic heterogeneity and implications for
      the treatment of high blood pressure.
AB  - The renal epithelial sodium channel (ENaC) is of fundamental importance in the
      control of sodium reabsorption through the distal nephron. ENaC is an important
      component in the overall control of sodium balance, blood volume and thereby of
      blood pressure. This is clearly demonstrated by rare genetic disorders of sodium
      channel activity (Liddle's Syndrome and Pseudohypoaldosteronism type 1 associated
      with contrasting effects on blood pressure). Subtle dysregulation of ENaC however
      may also be important in essential hypertension - a common condition and a major
      cause of cardiovascular morbidity and mortality. The epithelial sodium channel is
      formed from three partly homologous subunits. In this review we deals firstly
      with current views of structural and functional features of the renal epithelial
      sodium channel with particular emphasis on mechanisms and processes involved in
      the control of sodium channel activity at the biochemical and cellular levels. We
      then focus on genetic aspects with reference to the significance of genetic
      variation in the sodium channel genes in relation to blood pressure. In
      particular, we review recent investigations on the potential clinical
      significance of mutations within the genes encoding ENaC subunits in individuals
      with high blood pressure. Lastly, we also examine the potential value of
      pharmacological targeting of the renal epithelial sodium channel with the sodium
      channel inhibitor amiloride for the treatment of hypertension.

PMID- 16787252
TI  - CFTR chloride channel drug discovery--inhibitors as antidiarrheals and activators
      for therapy of cystic fibrosis.
AB  - The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a cAMP
      activated chloride channel expressed in epithelia in the lung, intestine,
      pancreas, testis and other tissues, where it facilitates transepithelial fluid
      transport. In the intestine CFTR provides the major route for chloride secretion
      in certain diarrheas. Mutations in CFTR cause the hereditary disease cystic
      fibrosis, where chronic lung infection and deterioration in lung function cause
      early death. CFTR is a well-validated targeted for development of inhibitors for
      therapy of secretory diarrheas and activators for therapy in cystic fibrosis. Our
      lab has identified and optimized small molecule inhibitors of CFTR, as well as
      activators of DeltaF508-CFTR, the most common mutant CFTR causing cystic
      fibrosis. High-throughput screening of small molecule collections utilizing a
      cell-based fluorescence assay of halide transport yielded thiazolidinone and
      glycine hydrazide CFTR inhibitors that block enterotoxin-mediated secretory
      diarrhea in rodent models, including a class of non-absorbable inhibitors that
      target the CFTR pore at its external entrance. Benzothiophene, phenylglycine and
      sulfonamide potentiators were identified that correct the defective gating of
      DeltaF508-CFTR chloride channels, and other small molecules that correct its
      defective cellular processing. Small molecule modulators of CFTR function may be
      useful in the treatment of cystic fibrosis, secretory diarrhea and polycystic
      kidney disease.

PMID- 16787253
TI  - The voltage-dependent anion channel (VDAC): function in intracellular signalling,
      cell life and cell death.
AB  - Research over the last decade has extended the prevailing view of mitochondria to
      include functions well beyond the critical bioenergetics role in supplying ATP.
      It is now recognized that mitochondria play a crucial role in cell signaling
      events, inter-organelle communication, aging, many diseases, cell proliferation
      and cell death. Apoptotic signal transmission to the mitochondria results in the
      efflux of a number of potential apoptotic regulators to the cytosol that trigger
      caspase activation and lead to cell destruction. Accumulating evidence indicates
      that the voltage-dependent anion channel (VDAC) is involved in this release of
      proteins via the outer mitochondrial membrane. VDAC in the outer mitochondrial
      membrane is in a crucial position in the cell, forming the main interface between
      the mitochondrial and the cellular metabolisms. VDAC has been recognized as a key
      protein in mitochondria-mediated apoptosis since it is the proposed target for
      the pro- and anti-apoptotic Bcl2-family of proteins and due to its function in
      the release of apoptotic proteins located in the inter-membranal space. The
      diameter of the VDAC pore is only about 2.6-3 nm, which is insufficient for
      passage of a folded protein like cytochrome c. New work suggests pore formation
      by homo-oligomers of VDAC or hetero-oligomers composed of VDAC and pro-apoptotic
      proteins such as Bax or Bak. This review provides insights into the central role
      of VDAC in cell life and death and emphasizes its function in the regulation of
      mitochondria-mediated apoptosis and, thereby, its potential as a rational target
      for new therapeutics.

PMID- 16787255
TI  - The impact of ancillary subunits on small-molecule interactions with voltage
      gated potassium channels.
AB  - Voltage-gated potassium channels (Kv channels) are the major determinants of
      cellular repolarization in excitable cells--they open in response to
      depolarization and facilitate selective efflux of potassium ions across the
      plasma membrane. Because of the importance of exquisitely timed cellular
      repolarization in controlling action potential morphology and duration, Kv
      channels are attractive therapeutic targets, particularly for drugs aimed at
      controlling aberrant electrical excitability such as is observed in cardiac
      arrhythmia and epilepsy. While the pore-forming alpha subunits of Kv channels are
      sufficient to form functional channels, a host of cytoplasmic and transmembrane
      ancillary subunits modulate their trafficking, function and regulation in vivo.
      Here, we consider the impact of ancillary subunits on Kv channel pharmacology,
      and discuss how increased understanding of the roles of ancillary subunits in
      native Kv channel complexes will lead to development of safer, more specific and
      more efficacious therapeutic small molecules.

PMID- 16787254
TI  - The cardiac hERG/IKr potassium channel as pharmacological target: structure,
      function, regulation, and clinical applications.
AB  - Human ether-a-go-go-related gene (hERG) potassium channels conduct the rapid
      component of the delayed rectifier potassium current, IKr, which is crucial for
      repolarization of cardiac action potentials. Moderate hERG blockade may produce a
      beneficial class III antiarrhythmic effect. In contrast, a reduction in hERG
      currents due to either genetic defects or adverse drug effects can lead to
      hereditary or acquired long QT syndromes characterized by action potential
      prolongation, lengthening of the QT interval on the surface ECG, and an increased
      risk for "torsade de pointes" arrhythmias and sudden death. This undesirable side
      effect of non-antiarrhythmic compounds has prompted the withdrawal of several
      blockbuster drugs from the market. Studies on mechanisms of hERG channel
      inhibition provide significant insights into the molecular factors that determine
      state-, voltage-, and use-dependency of hERG current block. In addition, crucial
      properties of the high-affinity drug binding site in hERG and its interaction
      with drug molecules have been identified, providing the basis for more refined
      approaches in drug design, safety pharmacology and in silico modeling. Recently,
      mutations in hERG have been shown to cause current increase and hereditary short
      QT syndrome with a high risk for life-threatening arrhythmias. Finally, the
      discovery of adrenergic mechanisms of hERG channel regulation as well as the
      development of strategies to enhance hERG currents and to modify intracellular
      hERG protein processing may provide novel antiarrhythmic options in
      repolarization disorders. In conclusion, the increasing understanding of hERG
      channel function and molecular mechanisms of hERG current regulation could
      improve prevention and treatment of hERG-associated cardiac repolarization
      disorders.

PMID- 16787256
TI  - Molecularly guided therapy of neuroblastoma: a review of different approaches.
AB  - Neuroblastoma (NB) is the most frequent extra-cranial solid tumor and the first
      cause of lethality in pre-school age children. NB accounts for 9-10% of pediatric
      tumors and affects more than ten thousand children a year. It originates from the
      sympathetic nervous system and is characterized by heterogeneous pathological and
      clinical presentation. Stage 4 NB represents approximately 50% of the cases and
      shows metastatic dissemination at onset; its prognosis is grim, with 20% of the
      patients surviving at 5 years from diagnosis in spite of aggressive chemotherapy
      with autologous hematopoietic stem cell support. Novel therapeutic strategies are
      urgently needed to improve the prognosis of stage 4 NB patients. Here we review
      the most promising approaches to NB treatment that have already reached clinical
      testing or have proved to be successful in preclinical models of the disease. All
      of these approaches are molecularly guided, since their rational development has
      benefited from the enormous amount of information on the biology of neuroblastoma
      gathered through molecular biology and genetics studies. The following topics are
      reviewed: MYCN oncogene amplification as parameter for therapeutic decision,
      minimal residual disease, immunotherapy, gene therapy, differentiation and
      apoptotic therapy, anti-angiogenic therapy, gene expression profiling as tool for
      generating novel therapeutic approaches. Although several efforts are still
      needed to reach a significant cure of patients with neuroblastoma, molecularly
      guided approaches have opened new ways to neuroblastoma treatment and can
      represent useful models for other cancers of either childhood or adulthood.

PMID- 16787257
TI  - Endocannabinoids: a new family of lipid mediators involved in the regulation of
      neural cell development.
AB  - The endocannabinoids (eCBs) anandamide and 2-arachidonoylglycerol are important
      retrograde messengers that inhibit neurotransmitter release via presynaptic CB1
      receptors. In addition, cannabinoids are known to modulate the cell
      death/survival decision of different neural cell types, leading to different
      outcomes that depend on the nature of the target cell and its
      proliferative/differentiation status. Thus, cannabinoids protect primary neurons,
      astrocytes and oligodendrocytes from apoptosis, whereas transformed glial cells
      are prone to apoptosis by cannabinoid challenge. Moreover, a potential role of
      the eCB system in neurogenesis and neural differentiation has been proposed.
      Recent research shows that eCBs stimulate neural progenitor proliferation and
      inhibit hippocampal neurogenesis in normal adult brain. Cannabinoids inhibit
      cortical neuron differentiation and promote glial differentiation. On the other
      hand, experiments with differentiated neurons have shown that cannabinoids also
      regulate neuritogenesis, axonal growth and synaptogenesis. These new observations
      support that eCBs constitute a new family of lipid signaling cues responsible for
      the regulation of neural progenitor proliferation and differentiation, acting as
      instructive proliferative signals through the CB1 receptor.

PMID- 16787258
TI  - Exploring the molecular function of PIN1 by nuclear magnetic resonance.
AB  - PIN1 participates in the regulation of a number of signalling pathways in the
      cell involving protein phosphorylation/dephosphorylation. Its role seems to be an
      essential control level in addition to the protein phosphorylation by proline
      directed kinases. Its cellular function includes regulation of the cell cycle by
      interaction with phosphorylated mitotic proteins such as Cdc25 and transcription
      factors such as p53. PIN1 was shown to be involved in the malignant
      transformation of cells in breast cancer, by up regulation of cyclinD1 and is
      thought to be involved in the development of the AD by regulating the function of
      phosphorylated Tau. We propose here to discuss the molecular function of PIN1 at
      the atomic level based on data from the recent literature and our own results
      obtained by the technique of Nuclear Magnetic Resonance. PIN1 specifically
      interacts with pThr/pSer-Pro motifs and is constituted by two domains: a WW N
      terminal domain that binds pThr/pSer-Pro epitopes and a prolyl cis/trans
      isomerase C-terminal catalytic domain. An exception to this organisation is found
      in the plant PIN1 homologous enzymes, like PIN1At from Arabidopsis thaliana, that
      are constituted of the sole catalytic domain. The molecular function of PIN1,
      binding to and isomerization of pThr/pSer-Pro bonds, are thought to lead to
      several functional consequences. In a first mode of action, exemplified by its
      competition with the CKS protein, the interaction with PIN1 prevents interaction
      with other regulatory proteins, like ubiquitin-ligases that lead to degradation
      pathways. In a second mode of action, the idea is largely accepted that the local
      isomerization modifies the global conformation of the protein substrate and hence
      its intrinsic activity, although this has never been directly demonstrated.
      Finally, isomerization catalysis is thought to regulate the (de)phosphorylation
      of specific pThr/pSer-Pro motifs, exemplified by the stimulation of the
      dephosphorylation of pThr231 of Tau by the PP2A phosphatase.

PMID- 16787259
TI  - Molecular dynamics of nicotinic acetylcholine receptor correlating biological
      functions.
AB  - The nicotinic acetylcholine receptor (nAChR) that mediates fast intercellular
      communication in response to neurotransmitters is a paradigm of ligand-gated ion
      channels. Molecular dynamics (MD) simulations are valuable in understanding
      membrane protein function at atomic level, providing useful clues for further
      experimental/theoretical studies. In this brief review, recent progress in MD
      simulations of the nAChR has been illustrated, mainly focusing on the latest
      simulation of the whole transmembrane domain of the receptor. On the basis of MD
      simulations, asymmetrical and asynchronous motions of five subunits were observed
      both in the ligand binding and transmembrane domains; a closed-to-open
      conformational shift of the gate was captured in different simulation systems;
      the contributions from the lipid molecules and other transmembrane segments
      rather than M2 to the gate switch as well as the conformational change of the
      whole channel were assessed; the dynamic behavior and related physical/chemical
      properties of the water molecules and cations within the ion channel were
      examined; and an experimentally comparable single-channel conductance and ion
      selectivity were obtained.

PMID- 16787260
TI  - Biological significance of polymorphism in legume protease inhibitors from the
      Bowman-Birk family.
AB  - Naturally occurring protease inhibitors (PI) of the Bowman-Birk type constitute a
      major PI family in cereal and legume seeds. The family name is derived from the
      names of the two investigators who characterised the first inhibitor of this
      type, the Bowman-Birk inhibitor from soybean (BBI). These proteins have the
      capacity to inhibit one or more of a range of serine proteases, including the
      digestive enzymes trypsin and chymotrypsin. PI from this family interact with the
      active sites of serine proteases in a 'canonical', i.e. substrate-like, manner
      via exposed reactive site loops of conserved conformation within the inhibitor.
      Multiple BBI variants can be found within and among species. A limited number of
      amino acids located within the inhibitory domain is responsible for the primary
      functional and biological activities of BBI-like proteins. However, sequence
      variation in binding loops, post-translational modifications at the amino- and
      carboxy-terminal ends, as well as differences in the multimeric nature of the
      inhibitors may act in combination to influence the functional properties and the
      physiological role of BBI-like proteins. Recently, BBI and proteins homologous to
      BBI (BBI-like proteins) have emerged as highly promising cancer chemopreventive
      agents. BBI has been shown to be capable of preventing or suppressing
      carcinogenic processes in a wide variety of in vitro and in vivo animal model
      systems. The potential exploitation of BBI-like proteins in human health
      promotion programmes will depend on elucidating in detail the molecular basis for
      the variation in biological activities among the many variant forms. New
      knowledge, derived both from the use of synthetic cyclic peptides that mimic the
      inhibitory loops of BBI-like proteins, and from genomic data pertaining to the
      structure of BBI gene classes, together facilitate the manipulation, screening
      and selection of appropriate variants through biotechnology.

PMID- 16787262
TI  - The roles of corticotropin-releasing factor-related peptides and their receptors
      in the cardiovascular system.
AB  - Corticotropin-releasing factor (CRF), CRF-related peptides and their receptors
      are present in the central nervous system and in peripheral tissues including the
      immune, reproductive and cardiovascular systems. CRF and urocortin (urocortin 1)
      bind to the CRF receptor type 1 (CRF(1) receptor) and the CRF receptor type 2
      (CRF(2) receptor), whereas urocortin 2 (formerly known as stresscopin related
      peptide) and urocortin 3 (formerly known as stresscopin) bind with high affinity
      to the CRF(2) receptor. Recent studies show that urocortin 1, urocortin 2 and
      urocortin 3 are potent regulators of cardiovascular function. This review
      highlights the role of cardiovascular CRF and related peptides and its relevance
      in mediating the adaptive response of the cardiovascular system to stressful
      conditions.

PMID- 16787263
TI  - Development of inhibitors of the aspartyl protease renin for the treatment of
      hypertension.
AB  - Renin is the rate-limiting enzyme in the renin-angiotensin-aldosterone system
      (RAS) which controls blood pressure and volume. The biological function of renin
      is to cleave the N-terminus of angiotensinogen releasing the decapeptide,
      angiotensin I (ANGI). Subsequently, angiotensin I is further processed by the
      angiotensin converting enzyme (ACE) to produce angiotensin II (ANGII). The RAS
      cascade is a major target for the clinical management of hypertension. Current
      clinical treatments include angiotensin converting enzyme inhibitors (ACEi) and
      ANGII receptor blockers (ARBs). As the rate-limiting enzyme in ANGII production,
      renin inhibitors have been pursued as an additional class of anti-hypertensives.
      Clinical studies conducted with renin inhibitors have shown them to be as
      effective as ACE inhibitors in lowering blood pressure. Most importantly,
      inhibitors of renin may have a number of potential advantages over ACEi and ARBs.
      Renin is specific for angiotensinogen and will not carry the ancillary
      pharmacology associated with ACEi or ARBs. To date, no renin inhibitors have made
      it to market. The development of these inhibitors has been hindered by poor
      bioavailability and complex synthesis. However, despite the pharmacokinetic
      challenges of designing renin inhibitors, the enzyme remains a promising target
      for the development of novel treatments for hypertension. This review will
      consist of an overview of renin biology, the pharmacology of renin and RAS and
      focus in on renin as a target for blood pressure regulation. We also cover the
      evaluation of renin inhibitors in animal models and clinical studies. Presently a
      number of new generation inhibitors of renin are in development with at least one
      in the clinic and these will be discussed. Finally we will discuss what might
      distinguish renin inhibitors from current therapeutic options and discuss other
      therapeutic indications renin inhibitors might have.

PMID- 16787261
TI  - Advances in homology protein structure modeling.
AB  - Homology modeling plays a central role in determining protein structure in the
      structural genomics project. The importance of homology modeling has been
      steadily increasing because of the large gap that exists between the overwhelming
      number of available protein sequences and experimentally solved protein
      structures, and also, more importantly, because of the increasing reliability and
      accuracy of the method. In fact, a protein sequence with over 30% identity to a
      known structure can often be predicted with an accuracy equivalent to a low
      resolution X-ray structure. The recent advances in homology modeling, especially
      in detecting distant homologues, aligning sequences with template structures,
      modeling of loops and side chains, as well as detecting errors in a model, have
      contributed to reliable prediction of protein structure, which was not possible
      even several years ago. The ongoing efforts in solving protein structures, which
      can be time-consuming and often difficult, will continue to spur the development
      of a host of new computational methods that can fill in the gap and further
      contribute to understanding the relationship between protein structure and
      function.

PMID- 16787264
TI  - Cellobiose dehydrogenase--a flavocytochrome from wood-degrading, phytopathogenic
      and saprotropic fungi.
AB  - Cellobiose dehydrogenase, the only currently known extracellular flavocytochrome,
      is formed not only by a number of wood-degrading but also by various
      phytopathogenic fungi. This inducible enzyme participates in early events of
      lignocellulose degradation, as investigated in several basidiomycete fungi at the
      transcriptional and translational level. However, its role in the ascomycete
      fungi is not yet obvious. Comprehensive sequence analysis of CDH-encoding genes
      and their translational products reveals significant sequence similarities along
      the entire sequences and also a common domain architecture. All known cellobiose
      dehydrogenases fall into two related subgroups. Class-I members are represented
      by sequences from basidiomycetes whereas class-II comprises longer, more complex
      sequences from ascomycete fungi. Cellobiose dehydrogenase is typically a
      monomeric protein consisting of two domains joined by a protease-sensitive linker
      region. Each larger (dehydrogenase) domain is flavin-associated while the smaller
      (cytochrome) domains are haem-binding. The latter shorter domains are unique
      sequence motifs for all currently known flavocytochromes. Each cytochrome domain
      of CDH can bind a single haem b as prosthetic group. The larger dehydrogenase
      domain belongs to the glucose-methanol-choline (GMC) oxidoreductase superfamily -
      a widespread flavoprotein evolutionary line. The larger domains can be further
      divided into a flavin-binding subdomain and a substrate-binding subdomain. In
      addition, the class-II (but not class-I) proteins can possess a short cellulose
      binding module of type 1 at their C-termini. All the cellobiose dehydrogenases
      oxidise cellobiose, cellodextrins, and lactose to the corresponding lactones
      using a wide spectrum of different electron acceptors. Their flexible specificity
      serves as a base for the development of possible biotechnological applications.

PMID- 16787266
TI  - Glial modulation of GABAergic and glutamat ergic neurotransmission.
AB  - Function of astroglia in the modulation of availability, release and clearance
      (inactivation) of Glu and GABA within the central nervous system is reviewed. Net
      synthesis of Glu through Gln synthetase exclusively localized in astrocytes can
      only occur by a metabolic coupling between neurons and astrocytes. Two (GLAST and
      GLT-1) of the five Glu transporters cloned preferentially expressed in astrocytes
      perform the astroglial Glu uptake of very high capacity. Moreover, astrocytes
      have been shown to mediate Glu release by a mechanism mimicking vesicular
      release. Biosynthesis of GABA in neurons is brought about by decarboxylation of
      Glu catalyzed by a pyridoxal phosphate requiring enzyme (GAD) that exists in two
      isoforms (GAD65 and GAD67) exhibiting different subcellular localization and
      regulatory properties. Detailed studies of GABA synthesis in GABAergic neurons
      using (13)C NMR spectroscopy have provided evidence for direct involvement of the
      tricarboxylic acid cycle. Synaptically released GABA taken up into surrounding
      astrocytes is converted to either CO(2) or Gln. Two reports on the release of
      GABA in rat dorsal root ganglia indicated that glial cells may perform GABA
      release as well. Gln formed from GABA in astrocytes can be transferred to
      GABAergic neurons and subsequently converted to GABA. Inhibition of either
      degradation or clearance of GABA has been successfully applied in the development
      of antiepileptics such as vigabatrin or tiagabine. So far, no specific strategy
      has been developed aimed at stimulating Glu transport.

PMID- 16787267
TI  - Extracellular level of GABA and Glu: in vivo microdialysis-HPLC measurements.
AB  - In spite of several studies showing specific physiological functions of changes
      in the extracellular level of the major excitatory and inhibitory transmitters,
      Glu and GABA within the brain ([Glu](EXT), [GABA](EXT)) the exact origin
      (neuronal vs. astroglial, synaptic vs. extrasynaptic) of Glu and GABA present in
      dialysate samples is still a matter of debate. For better understanding the
      significance of in vivo microdialysis data, here we discuss methodological
      details and problems in addition to regulation of [Glu](EXT) and [GABA](EXT).
      Changes in [Glu](EXT) and [GABA](EXT) under pathological conditions such as
      ischemia and epilepsy are also reviewed. Based on recent in vivo microdialysis
      data we argue that ambient [Glu](EXT) and [GABA](EXT)may have a functional role.
      It is suggested that specific changes in concentrations of Glu and GABA in
      dialysate samples together with their alterations independent of neuronal
      activity indicate the involvement of Glu and GABA in the information processing
      of the brain as essential signaling molecules of nonsynaptic transmission as
      well. Since various drugs are able to interfere with extrasynaptic signals in
      vivo, studying the extracellular cell-to-cell communication of brain cells
      represents a new aspect to improve drugs modulating Gluergic as well as GABAergic
      neurotransmission.

PMID- 16787268
TI  - Nonsynaptic receptors for GABA and glutamate.
AB  - The concept of nonsynaptic communication between neurons, once a heretic idea,
      has become a self-evident fact during the almost forty years since its original
      discovery. In this review we investigate whether the archetypical synaptic
      transmitters of the central nervous system, Glu and GABA, can operate via
      nonsynaptic transmission. While experimental data supporting the general concept
      of nonsynaptic transmission has been progressively accumulating during these
      years, most of the evidence regarding nonsynaptic transmission by Glu and GABA
      are results of the last decade. In this paper we collect evidence for different
      forms of nonsynaptic transmission by the Gluergic and GABAergic system. We
      investigate two theoretical predictions of the concept of nonsynaptic
      transmission in the light of recent progress in the field: i) since extrasynaptic
      receptors experience a lower concentration of agonist, they are likely to have
      higher affinity for the agonist ii) extrasynaptic receptors are expected to be
      more important pharmacological targets.

PMID- 16787269
TI  - Glutamate as a modulator of embryonic and adult neurogenesis.
AB  - It has been widely accepted that neurogenesis continues throughout life. Neural
      stem cells can be found in the ventricular zone of the embryonic and in
      restricted regions of the adult central nervous system, including subventricular
      and subgranular zones of the hippocampal dentate gyrus. The network of signaling
      mechanisms determining whether neural stem cells remain in a proliferative state
      or differentiate is only partly discovered. Recent advances indicate that
      glutamate (Glu), the predominant excitatory neurotransmitter in mature neurons,
      can influence immature neural cell proliferation and differentiation, as well.
      Despite many similarities, Glu actions on neurogenesis in the developing and
      adult brain show distinct differences and are far from being clear. Due to
      alterations of Glu transport mechanisms, extracellular Glu level is high in the
      embryonic CNS. Glu acts non-synaptically on dividing progenitors either by
      directly activating ionotropic and/or metabotropic Glu receptors or can influence
      other cells which are located in the vicinity of proliferating cells and produce
      molecules regulating neural precursor cell proliferation by other mechanisms. Due
      to the complexity of signaling pathways and to regional differences in neural
      precursors, Glu can influence proliferation and neuronal commitment as well, and
      acts as a positive regulator of neurogenesis. Brain injuries like ischemia,
      epilepsy or stress lead to severe neuronal death and additionally, influence
      neurogenesis, as well. Glu homeostasis is altered under these pathological
      circumstances, implying that therapeutic treatments mediating Glu signaling might
      be useful to increase neuronal replacement after cell loss in the brain.

PMID- 16787270
TI  - Trophic effect of glutamate.
AB  - During development, Glu receptors and N-methyl-D-aspartate receptors in
      particular initiate a cascade of signal transduction events and gene expression
      changes primarily involving Ca(2+) ion-mediated signaling induced by activation
      of either Ca(2+) ion-permeable receptor channels or voltage-sensitive Ca(2+) ion
      channels. The consecutive activation of major protein kinase signaling pathways,
      such as Ras-MAPK/ERK and PI3-K-Akt, contributes to regulation of gene expression
      through the activation of key transcription factors, such as CREB, SRF, MEF-2, NF
      kappaB. Metabotropic Glu receptors can also engage these signaling pathways and
      this may be mediated, in part, by transactivating receptor tyrosine kinases.
      Indirect effects of Glu receptor stimulation are due to the production and
      release of neurotrophic factors, such as brain derived neurotrophic factor and
      also involve glia-neuronal interaction through Glu-induced release of trophic
      factors from glia. The trophic effect of Glu receptor activation is developmental
      stage-dependent and may play an important role in determining the selective
      survival of neurons that made proper connections. During this sensitive
      developmental period interference with Glu receptor function may lead to
      widespread neuronal loss. However, NMDA receptor blockade-induced
      neurodegeneration can also occur in the adult brain. Depending on the stimulus
      strength, Glu receptors mediate biphasic effects. In addition to synaptic
      transmission, physiological stimulation of Glu receptors can mediate trophic
      effects and promote neuronal plasticity. Excessive stimulation is neurotoxic.
      Attention must, therefore, be paid to these features, when therapeutic
      manipulation of excitatory amino acid receptors is considered in the clinical
      setting.

PMID- 16787271
TI  - Functional significance of co-localization of GABA and Glu in nerve terminals: a
      hypothesis.
AB  - Salient features of the co-transmission by GABA and Glu in neural signaling are
      summarized. Experimental data have been accumulating which demonstrate; i) GABA
      immunoreactivity in and GABA-release from constitutively Gluergic hippocampal
      mossy fibre terminals, ii) plasticity of the GABAergic phenotype of
      constitutively Gluergic granule cells of the Dentate Gyrus, iii) expression of
      GABA(A) receptor gamma(3) subunit in the mossy fibre termination zone in the CA3
      subfield, iv) co-labeling of terminals for GABA and Glu in the retina, brain stem
      and spinal cord, and v) functional compatibility of vesicular Glu (VGLUT3) and
      GABA (VIAAT) transporters. It is not clear, however, whether or not Glu and GABA
      are released from the same terminals, and packaged in the same vesicles. Using
      multiple transmitters neurons may serve to reduce the metabolic cost and errors
      of signaling.

PMID- 16787272
TI  - Co-existence of GABA and Glu in the hippocampal granule cells: implications for
      epilepsy.
AB  - The granule cells of the Dentate Gyrus are one of the most exciting and
      intriguing cells in the central nervous system. Besides containing and releasing
      Glu, they have been shown to contain and release peptides (somatostatin,
      neuropeptide Y, neurokinin B, cholecystokinin, dynorphin, enkephalin), Zn(++)
      ion, and brain-derived neurotrophic factor (BDNF). The recent addition of GABA to
      this list suggests that these cells can also function as inhibitory cells.
      Indeed, evidence has been presented of co-localization of all markers of the
      GABAergic phenotype in granule cells: GABA, the enzyme for its synthesis (Glu
      decarboxylase) and the membrane and vesicular transporters of GABA. These markers
      of the GABAergic phenotype are up-regulated after epileptic seizures. When this
      occurs, monosynaptic GABA receptor-mediated transmission emerges in the mossy
      fiber synapse thus restraining excitation and mediating antiepileptic and
      neuroprotective actions.

PMID- 16787273
TI  - Co-existence of GABA and Glu transporters in the central nervous system.
AB  - Co-localization of transporters able to recapture the released or endogenously
      synthesized transmitter (homotransporters) and of transporters that can
      selectively take up transmitters/modulators originating from neighbouring
      structures (heterotransporters) has been demonstrated to occur within the same
      axon terminal of several neuronal phenotypes. Activation of terminal
      heterotransporters invariably leads to the release of the transmitter specific to
      the terminal. Heterotransporters are also increasingly reported to exist on
      neuronal soma/dendrites and nerve terminals, on the basis of morphological
      experiments. The functions of somatodendritic heterotransporters has been
      investigated only in a very limited number of cases. Release-regulating GABA
      heterotransporters of the GAT-1 type exist on Glu nerve terminals in different
      rodent brain regions including spinal cord. Activation of GABA heterotransporters
      provokes release of Glu, which takes place by reversal of the Glu homotransporter
      and by anion channel opening. Interestingly, the release of Glu induced by GABA
      in spinal cord is dramatically enhanced in a transgenic mouse model of
      amyotrophic lateral sclerosis and this effect seems to represent the most
      precocious mechanism that increases extracellular Glu concentration, reported to
      occur in the pathomechanism.

PMID- 16787274
TI  - Role for GABA and Glu plasma membrane transporters in the interplay of inhibitory
      and excitatory neurotransmission.
AB  - Neurotransmitter plasma membrane transporters do have much more to perform than
      simply terminating synaptic transmission and replenishing neurotransmitter pools.
      Findings in the past decade have evidenced their function in maintaining
      physiological synaptic excitability, and their actions in critical or
      pathological conditions, also. Conclusively these findings indicated a previously
      unrecognized role for neurotransmitter plasma membrane transporters in both,
      synaptic and nonsynaptic signaling. Major inhibitory and excitatory
      neurotransmitters within the brain, GABA and Glu, have long been considered to
      operate through independent systems (GABAergic or Gluergic), each of them
      characterized by its own localization, function and dedicated GABAergic or
      Gluergic cell phenotypes. Recent advances, however, have challenged this long
      standing paradigm. Localization of GABA in Gluergic terminals and Glu in
      GABAergic cells were reported. Specific plasma membrane transporters for GABA and
      Glu are also co-localized in different brain areas. Although, their role in
      regulating each other's signal is still far from being understood, emerging lines
      of evidence on interplaying GABAergic and Gluergic processes through plasma
      membrane transporters opens up a new avenue in the field of more specific
      therapeutic intervention.

PMID- 16787276
TI  - K(v)7 channels: function, pharmacology and channel modulators.
AB  - K(v)7 channels are unique among K(+) channels, since four out of the five channel
      subtypes have well-documented roles in the development of human diseases. They
      have distinct physiological functions in the heart and in the nervous system,
      which can be ascribed to their voltage-gating properties. The K(v)7 channels also
      lend themselves to pharmacological modulation, and synthetic openers as well as
      blockers of the channels, regulating neuronal excitability, have existed even
      before the K(v)7 channels were identified by cloning. In the present review we
      give an account on the focused efforts to develop selective modulators, openers
      as well as blockers, of the K(v)7 channel subtypes, which have been undertaken
      during recent years, along with a discussion of the K(v)7 ion channel physiology
      and therapeutic indications for modulators of the neuronal K(v)7 channels.

PMID- 16787277
TI  - Pharmacological roles of the large-conductance calcium-activated potassium
      channel.
AB  - The gating of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel is
      primarily controlled by intracellular Ca(2+) and/or membrane depolarization.
      These channels play a role in the coupling of excitation-contraction and stimulus
      secretion. A variety of structurally distinct compounds may influence the
      activity of these channels. Squamocin, an Annonaceous acetogenin, could interact
      with the BK(Ca) channel to increase the amplitude of Ca(2+)-activated K(+)
      current in coronary smooth muscle cells. Its stimulatory effect is related to
      intracellular Ca(2+) concentrations. In inside-out patches, application of
      ceramide to the bath suppressed the activity of BK(Ca) channels recorded from
      pituitary GH(3) cells and from retinal pigment epithelial cells. ICI-182,780, an
      estrogen receptor antagonist, was found to modulate BK(Ca)-channel activity in
      cultured endothelial cells and smooth muscle cells in a mechanism unlinked to the
      inhibition of estrogen receptors. Caffeic acid phenethyl ester (CAPE) and its
      analogy, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, could directly increase the
      activity of BK(Ca) channels in GH(3) cells. CAPE also reduced the frequency and
      amplitude of intracellular Ca(2+) oscillations in these cells. The CAPE
      stimulated activity in BK(Ca) channels is thought to be unassociated with its
      inhibition of NF-kappaB activation. Cilostazol, an inhibitor of cyclic nucleotide
      phosphodiesterase, could stimulate BK(Ca) channel-activity and reduce the firing
      of action currents simultaneously in GH(3) cells. Therefore, the regulation by
      these compounds of BK(Ca) channels may in part be responsible for their
      regulatory actions on cell functions.

PMID- 16787278
TI  - Structure-activity relationships of K(ATP) channel openers.
AB  - Given their many physiological functions, K(ATP) channels represent promising
      drug targets. Sulfonylureas like glibenclamide block K(ATP) channels; they are
      used in the therapy of type 2 diabetes. Openers of K(ATP) channels (KCOs) e.g.
      relax smooth muscle and induce hypotension. KCOs are chemically heterogeneous and
      include as different classes as the benzopyrans, cyanoguanidines, thioformamides,
      thiadiazines and pyridyl nitrates. Examples for new chemical entities more
      recently developed as KCOs include cyclobutenediones, dihydropyridine related
      structures, and tertiary carbinols. Structure-activity relationships of the main
      chemical classes of KCOs are discussed.

PMID- 16787279
TI  - From cromakalim to different structural classes of K(ATP) channel openers.
AB  - ATP-Sensitive potassium channel openers (K(ATP)COs) are a group of compounds with
      a broad spectrum of potential therapeutic applications, as they constitute
      efficient tools for dampening cell excitability. Interest in the K(ATP)COs was
      triggered in the early 1980s by the discovery of the benzopyran-based structure
      cromakalim (CRK), which is a powerful smooth muscle relaxant. CRK can be
      considered the archetype of K(ATP)COs and is by far the most mimicked structure.
      In many structure-activity studies various substitutions have been made at the
      different positions of the benzopyran ring permitting the optimal activity to be
      correlated with a specific set of structural characteristics and stereochemical
      features of the molecule. Thus, many potent benzopyran derivatives have been
      identified. The benzopyran nucleus itself has also been modified in both the
      aromatic ring and in the pyran moiety. The intention of this review is to bring
      together all the different structural classes of K(ATP)COs arising from the
      replacement of CRK benzopyran-based structure with various ring systems; design,
      structure-activity relationship, and synthesis will be given.

PMID- 16787280
TI  - Nucleoside analogs as anti-HBV agents.
AB  - Chronic hepatitis B virus (HBV) infection affects about 400 million people
      worldwide. The development of nucleoside analogs that inhibit HBV polymerase
      provides an important approach for treating HBV infection. The approval of
      lamivudine, adefovir and entecavir represents a cornerstone of hepatitis B
      therapy. However, the challenges from the resistance and the off-therapy viral
      rebound are still unmet, and there is a need of developing new therapeutic
      agents. This review will discuss the structure-activity relationship of the most
      significant anti-HBV nucleoside analogs and the latest development in the field.

PMID- 16787281
TI  - Progress in 7-deazapurine - pyrrolo[2,3-d]pyrimidine - ribonucleoside synthesis.
AB  - This review reports on the synthesis of 7-deazapurine ribonucleosides, including
      C-nucleosides, 2'-C-methyl derivatives and L-enantiomers. It covers the various
      aspects of convergent nucleoside synthesis such as the Schiff base procedure, the
      fusion reaction, the metal salt procedures, the Silyl-Hilbert-Johnson reaction,
      and the nucleobase anion glycosylation. The review discusses the scope and
      limitations of glycosylation reactions performed on 7-deazapurines. Peracylated
      ribose derivatives were now employed in the glycosylation, which overcome
      difficulties reported earlier.

PMID- 16787282
TI  - RNA Interference with chemically modified siRNA.
AB  - siRNA has become an indispensable tool for functional characterization of genes.
      It has also demonstrated tremendous potential as a new generation of drug
      candidates. Although the technology works very well to a great panel of cells in
      vitro, it is still a challenge to translate the success into in vivo target
      validation easiness and, even more difficult, into therapeutic applications. With
      a number of chemically modified compounds under initial clinical trial from
      several commercial entities, the interests in chemical modification of siRNA have
      become heightened. In this review we have tried to touch on most of the chemical
      modifications of RNA that have been tested in the siRNA landscape, but maintained
      a focus on the backbone modifications, and 2'-modifications on the ribose ring.
      It is anticipated that more modifications and more systematic comparisons between
      different modifications will be performed to draw more educated conclusions over
      some of the modifications.

PMID- 16787283
TI  - RNA interference and potential applications.
AB  - RNA interference (RNAi) is the process of using specific sequences of double
      stranded RNA (dsRNA) to knock down the expression level of sequence-homologous
      genes. Such ability of small interfering RNA (siRNA) in mammalian cells will
      undoubtedly revolutionize the study of functional genomics, the discovery of drug
      targets and even the treatment of human diseases. In this review we briefly
      describe the history of RNAi discovery, the RNAi mechanism and the general
      guideline for siRNA design as well as various methods for siRNA production and
      delivery. We also introduce the potential applications of siRNA, inducible siRNA
      and siRNA library in speeding up basic biomedical research and in acting as
      potential therapeutic agents for treatment of numerous human diseases.

PMID- 16787284
TI  - Chemical and structural diversity of siRNA molecules.
AB  - Short interfering RNAs (siRNAs) are 21-23 nt long double-stranded
      oligoribonucleotides which in mammalian cells exhibit a potency for sequence
      specific gene silencing via an RNA interference (RNAi) pathway. It has been
      already proven that exogenous, chemically synthesized siRNA molecules are
      effective inhibitors of gene expression and are widely applied for analysis of
      protein function and proteomics-based target identification. Moreover, since
      their discovery siRNA molecules have been implemented as potential candidates for
      therapeutic applications. Variously modified siRNA molecules containing sugar
      modifications (2'-OMe, -F, -O-allyl, -amino, orthoesters and LNA analogues),
      internucleotide phospodiester bond modifications (phosphorothioates,
      boranophosphates), base modifications (s(2)U) as well as 3'-terminal cholesterol
      conjugated constructs were investigated as potential candidates for effective
      inhibition of gene expression. This chapter reviews an impact of chemical and
      structural modifications of siRNA molecules on their serum and thermal stability,
      cellular and in vivo activity, cellular uptake, biodistribution and cytotoxicity.
      Functional analysis of chemically modified siRNA molecules allows for better
      understanding of the mechanism of the RNA interference process as well as
      demonstrates immense efforts in optimizing in vivo potency of siRNA molecules for
      RNAi-based drug design.

PMID- 16787286
TI  - Gender and susceptibility to sepsis following trauma.
AB  - An analysis of current literature on sexual dimorphism in response to trauma
      hemorrhage revealed conflicting reports on the role of gender in outcomes of
      trauma patients. In contrast, results obtained from experimental studies clearly
      support the suggestion that gender plays a significant role in post injury
      pathogenesis. As discussed in this review, experimental studies suggest that the
      suppression of immune and cardiac function is severe in males and ovariectomized
      females; however, both immune and cardiac functions are maintained in proestrus
      females. Furthermore, findings from a number of studies have shown that the
      depletion of male sex hormones by castration or by blocking the interaction
      between male sex steroids and their receptors in males prevented the suppression
      of both immune and cardiac functions following trauma-hemorrhage. Moreover,
      administration of estrogen in males and ovariectomized females also prevented the
      suppression of immune and cardiac functions following trauma-hemorrhage. Thus,
      these experimental findings collectively suggest that female sex hormones (i.e.,
      estrogen) produce salutary effects following trauma-hemorrhage whereas male sex
      steroids (i.e. 5alpha-dihydrotestosterone, 5alpha-DHT) are suppressive to immune
      and cardiac functions under those conditions. Such dramatic differences in the
      outcome of trauma-hemorrhage in proestrus females and males clearly suggest that
      the prevailing sex hormonal levels at the time of injury play a critical role in
      shaping the host response to trauma-hemorrhage. While a definitive cause for the
      conflicting data obtained in the clinical setting remains to be established, the
      discrepancy could be due to the differences in the hormonal levels at the time of
      injury. Since there is no information on hormonal status in the clinical studies,
      it is difficult to ascertain the role of sex hormones in post trauma
      pathogenesis. Therefore, in order to establish the role of gender in the outcome
      of trauma patients, more planned studies are needed in which the levels of sex
      hormones should be measured at the time of hospital admission. Furthermore, more
      studies, both in the clinical and experimental settings, should be performed to
      determine the mechanism by which the sex hormones improve immune and organ
      functions following trauma-hemorrhage. The findings obtained from these studies
      will help in designing innovative therapeutic approaches for the treatment of
      trauma patients.

PMID- 16787287
TI  - Neuro-immune-endocrine mechanisms during septic shock: role for nitric oxide in
      vasopressin and oxytocin release.
AB  - Septic shock is a major cause of death following trauma and a persistent problem
      in surgical patients. It is a challenge to the critical care medicine specialist
      and carries an unacceptably high mortality rate, despite adequate antibiotic and
      vasopressor therapy. The prevalent hypothesis regarding its mechanism is that the
      syndrome is caused by an excessive defensive and inflammatory response. During
      the acute phase some signalling mechanisms are activated, particularly hormone
      release, which function to restore the host homeostasis that has been disturbed
      by the infection. Since the neuroendocrine and immune systems are functionally
      related, so the exposure to antigens induces a synchronized response, which
      allows the organism to successfully endure immunology changes. An important
      characteristic of this communication includes the appearance of proteins released
      into the circulation by activated immune cells. These proteins, called cytokines
      can enter the circulation and reach neuroendocrine organs, where they act either
      themselves or through the release of intermediates such as prostaglandin,
      catecholamines and nitric oxide. The synthesis of nitric oxide may be induced in
      brain as a consequence of infection and may alter the function of the
      hypothalamic-pituitary axis. In this review we discuss the physiologic roles of
      the nitric oxide in central nervous system controlling the regulation of
      vasopressin and oxytocin during the pathophysiology of sepsis.

PMID- 16787288
TI  - Bacterial translocation, microcirculation injury and sepsis.
AB  - Sepsis is the result from a complex bacterial-host interaction, which is an often
      fatal response when host protective molecular mechanisms designed to fight
      invading bacteria surpass the beneficial intensity to the point of causing injury
      to the host. Increasing evidences have implicated the bacterial translocation
      (BT) as the main source for the induction of sepsis, although the beneficial
      effect of BT process has been related to the development of the intestinal immune
      response by physiological interaction between bacteria and host. In this article,
      we examined evolving concepts concerning to BT and discussed about its potential
      role in the promotion of microcirculation injury, moreover, its possible
      participation in the sepsis induction. According to our data obtained from in
      vivo BT animal-model, both bacterial overgrowth and bacterial pathogenic
      determinants seem to be major predisposing factors for the induction of BT.
      Besides, translocation of luminal bacteria through the lymphatic via elicits the
      activation of the GALT inflammatory response contributing to microcirculation
      injuries, and the haematological via of BT was responsible to the systemic
      bacterial spread. On other hand, the combination of BT process to the pre
      existing host systemic infection played a crucial role in the worsening of the
      clinical outcome. In our understanding, studies concerning to intestinal immune
      response and the pathophysiology of bacterial-host interaction, under normal and
      disease conditions, seems to be the key elements to the development of
      therapeutic approaches towards sepsis.

PMID- 16787289
TI  - Neutrophil function in severe sepsis.
AB  - Sepsis and septic shock continue to be a major cause of morbidity and mortality
      in critically ill patients. During the onset of sepsis, several inflammatory
      mediators, including cytokines, chemokines and nitric oxide are released
      systemically and mediate most of the pathophysiological events present in sepsis
      and septic shock, such as cardiovascular dysfunction and target-organ lesions.
      Polymorphonuclear leukocytes are critical effector cells during the inflammatory
      process and their migration to the infection focus is extremely important for the
      local control of bacterial growth and consequently for the prevention of
      bacterial dissemination. In experimental models and in human sepsis a profound
      failure of neutrophil migration to the infection focus is observed. It seems that
      the failure of neutrophil migration is dependent on toll-like receptor 4 (TLR4)
      and mediated by cytokines and chemokines, which induce the production of nitric
      oxide that inhibits neutrophil adhesion to venular endothelium and also the
      neutrophil chemotactic ability.

PMID- 16787290
TI  - Redox mechanisms of vascular cell dysfunction in sepsis.
AB  - Sepsis remains one of the leading causes of death in intensive care units,
      despite recent acquired knowledge on pathophysiology and treatment. Several
      mediators of inflammation and cellular damage have been implicated in the complex
      host-pathogen interaction underlying organ damage and multisystem organ failure ,
      which are hallmarks of sepsis and common causes of death. Among such mediators,
      reactive oxygen/nitrogen species have been increasingly studied in the context of
      direct cytotoxicity as well as altered cell signaling. While the generation of
      reactive oxygen species by inflammatory cells in sepsis is well known, recent
      studies have shown that vascular cells are able to release reactive oxygen
      intermediates that may be associated with endothelial dysfunction of sepsis.
      These compounds can activate transcription factors such as NF-kappaB that sustain
      inflammatory process or enzymatic systems like poly(ADP-ribose) polymerase-1,
      which are involved in apoptosis and cytotoxicity of sepsis. Our laboratory
      recently showed that platelet-derived exosomes from septic patients carry
      components of a superoxide-producing NADPH oxidase and can, at least in vitro,
      induce apoptosis of endothelial and vascular smooth muscle cells by a ROS
      dependent pathway. Taken together, these data show that reactive oxygen species
      are involved in cell signaling and organ injury in sepsis. Efforts must be made
      to identify the precise contribution of these factors in septic process, in order
      to clarify the mechanisms associated with the disease. This will certainly lead
      to discovery of therapeutic strategies that can help us to mitigate vascular
      dysfunction of sepsis.

PMID- 16787291
TI  - Nitric oxide and cardiovascular dysfunction in sepsis.
AB  - Sepsis and septic shock are the major causes of morbidity and mortality in
      critically ill patients. During the onset of sepsis, a massive inflammatory
      reaction involving chemical mediators such as cytokines and chemokines and
      inflammatory cells such as the polymorphonuclear neutrophil and macrophage takes
      place. In addition to this systemic inflammatory process, sepsis and septic
      shocks cause a profound decrease in the peripheral vasomotor tone leading to a
      great decrease in the peripheral resistance. This event is central to derangement
      of hemodynamic and perfusion parameters. Nitric oxide (NO) is produced by several
      cell types and has been implicated in a wide range of physiological and
      pathological processes, with both detrimental and beneficial effects. There is a
      wealth of data implicating NO as a key player in all cardiac, vascular, renal and
      pulmonary derangements of sepsis and septic shock. Clinical assays trying to
      improve sepsis by inhibiting NO formation by NO synthases have met with failure,
      probably due to the lack of selectivity of inhibitors towards NOS isoforms.
      Notwithstanding the search for selective inhibitors, a better understanding of
      the NO molecular effector mechanisms may provide new opportunities for therapy
      development. Some of these NO effector mechanisms are discussed, including
      guanylate cyclase, nitrosothiols, potassium channels, reactive oxygen species and
      gene expression in the context of sepsis. Thus, more research on the relationship
      between NO and sepsis is clearly needed and warranted and may provide new
      therapeutic targets to treat sepsis and septic shock.

PMID- 16787292
TI  - Coagulation and sepsis.
AB  - Sepsis is a complex disease and coagulation derangements are part of this
      context. The inflammatory storm is ultimately responsible for coagulation
      derangements. It is characterized by exacerbated coagulation, impaired
      anticoagulation and decreased fibrin removal. These derangements are implicated
      in the generation of microcirculation thrombosis, with deposition of microclots
      and obstruction of circulation, impairing blood flow and contributing to tissue
      hypoperfusion and consequently, organ dysfunction. This review will address the
      main issues regarding coagulation disorders in the context of sepsis.

PMID- 16787293
TI  - Bacterial recognition and induced cell activation in sepsis.
AB  - The pathogenesis of sepsis involves complex interaction between the host and the
      infecting microorganism. Recognition and processing of microorganism antigens are
      essential functions of the cells of innate immune systems, and will ultimately,
      through the antigen presentation to the cells of adaptive immunity and the
      synthesis and secretions of mediators, such as cytokines, drive a coordinated
      immune response. Neutrophils and monocytes will therefore function as sensing and
      effectors cells. Fundamental in this process is the ability to discriminate self
      from non-self molecules. Of major interest in sepsis is that the protective and
      damaging host responses are part of the same process, that is, the inflammatory
      response that controls the infection process also underscores many of the
      pathophysiological events of sepsis. Moreover, this is a dynamic process
      according to the continuum of sepsis and its complications; up and down
      regulation of cellular activities may be differently regulated in different
      tissues, different cells and even in different functions of the same cell. This
      review will focus on microorganism recognition and signalization in sepsis, with
      emphasis on the neutrophils and monocytes adaptation during the ongoing disease.

PMID- 16787294
TI  - Pathogenesis-oriented targets for adjunctive therapy.
AB  - The outcome of patients with sepsis arises from multiple factors affecting both
      the host and the invading microorganisms. Even within the setting of adequate
      antimicrobial use, patients still die of sepsis. Thus, strategies focusing on
      further therapy targets are an important area of interest for basic and clinical
      research. Although such adjunctive sepsis therapy has failed to achieve
      consistent better survival rates so far, the progress in understanding of the
      pathophysiology of sepsis seen in recent years is so profound, that the
      possibility that a new and effective treatment may arise should be warmly
      considered. Indeed, it may be considered that efficacious interventions, such as
      early and vigorous fluid replacement, strict blood glucose control, low-dose
      corticosteroid reposition, protective mechanical ventilation and activated
      protein C are pathogenic-oriented targets of therapy. In this paper we aim to
      review some aspects of the pathogenesis of sepsis, focusing on possible targets
      for adjunctive therapy. Published clinical trials and experimental data
      supporting such trials are commented on.

PMID- 16787295
TI  - Mechanisms of action of hypertonic saline resuscitation in severe sepsis and
      septic shock.
AB  - Small volumes of 7.5% NaCl (2400mOsm/L) have been extensive evaluated in animal
      models of hemorrhagic shock and in clinical trials of post-traumatic hypotension
      and as volume support for complex cardiovascular procedures. Hypertonic solutions
      promote immediate blood volume expansion, restore cardiac output and regional
      blood flows, improve microcirculation and modulate immune responses, thereby
      decreasing inflammatory responses triggered by shock and trauma. A large number
      of very interesting in vivo and in vitro experiments highlighted that hypertonic
      saline resuscitation may decrease susceptibility to post-traumatic sepsis,
      modulate trauma and sepsis-induced immune dysfunction, inflammatory response and
      apoptosis. All those long-term benefits associated with hypertonic resuscitation
      may be of potential relevance for the management of severe sepsis and septic
      shock In this review, we describe the mechanisms of action of hypertonic saline
      based on experimental studies as well as its efficacy and safety based on its
      clinical use. We believe those studies support the need for additional
      experimental and clinical studies before the widespread use of hypertonic
      solutions for the treatment of severe sepsis and septic shock.

PMID- 16787296
TI  - Epidemiology of severe sepsis around the world.
AB  - Severe sepsis is an ongoing challenge for clinicians and health-care
      administrators mainly because is associated with a high incidence, mortality rate
      and costs. In recent years, several epidemiological studies about the incidence
      of sepsis have come out in different and prestigious journals. However, it is not
      advisable to draw direct conclusions from those studies considering
      methodological flaws or even different approaches. Hence, we have to be familiar
      with those obstacles and know how to overcome them. This review paper highlights
      the methods which have been used in these studies and depicts the results of
      occurrence rate or incidence of sepsis in countries and in intensive care units.

PMID- 16787297
TI  - The lung in sepsis: guilty or innocent?
AB  - The mortality rate of severe sepsis is still high (20 to 65%) despite the
      advances in critical care. The most important determinant of the prognosis in
      this condition is the occurrence of multiple organ dysfunction syndrome (MODS).
      The lung is the most frequently identified organ to fail in sepsis and is also
      the most frequent primary site of infection. The development of acute respiratory
      distress syndrome (ARDS) is common in those cases. The current understanding of
      the pathogenesis of ARDS suggests that the degree of inflammatory response and
      its sustained leukocyte activation may determine the clinical evolution of ARDS.
      The way that mechanical ventilation is delivered is responsible for the start
      and/or the perpetuation of a pro-inflammatory cascade activation that, due to the
      loss of the alveolar compartmentalization in ARDS, can reach the bloodstream and
      induce MODS. On the other hand, during sepsis, the alveolar compartmentalization
      is lost, allowing the passage of cytokines, released to the bloodstream by any
      other organ, to the pulmonary endothelium. These cytokines, especially IL-1, TNF
      alpha and IL-8, have important roles in the lung dysfunction. Experimental and
      clinical studies have been demonstrated that ventilation strategies using low
      tidal volumes and limitation of airway pressures can block cytokines and reduce
      mortality of patients with respiratory failure. The studies are still
      insufficient to determine the role of pharmacological therapies in those
      patients.

PMID- 16787298
TI  - Surviving sepsis campaign: a project to change sepsis trajectory.
AB  - Sepsis is an acute and severe disease associated with early and late high
      mortality, high and growing prevalence, and impressive costs. In October 2002,
      during the European Society of Intensive Care Medicine annual congress, the
      Surviving Sepsis Campaign was launched through a "Barcelona Declaration" -- a
      document calling critical care providers, governments, health agencies and lay
      people to join the fight against sepsis. The aim of the campaign was to reduce
      the sepsis mortality rate by 25% within 5 years (actually, this deadline has been
      ended from 2007 to 2009). In 2003, a group of international critical care and
      infectious disease experts in the diagnosis and management of infection and
      sepsis met to develop guidelines that the bedside clinician could use to improve
      the outcome of severe sepsis and septic shock. A comprehensive document created
      from the committee's deliberations was published in prestigious journals. Thus,
      the SSC is a global, multi-organizational initiative to fight sepsis and
      undoubtedly, this campaign is a historic step for critical care medicine. This
      paper highlights the recommendations and the strategies proposed by SSC to
      implement them in intensive care units.

PMID- 16787300
TI  - Discovery and development of VX-950, a novel, covalent, and reversible inhibitor
      of hepatitis C virus NS3.4A serine protease.
AB  - The hepatitis C virus (HCV) NS3.4A protease, which is essential for viral
      replication, is considered one of the most attractive targets for developing
      novel anti-HCV therapies. However, discovery of potent and selective small
      molecule inhibitors of HCV NS3.4A protease as oral drug candidates has been
      hampered by the shallow substrate-binding groove of the protease. Serine trap
      warheads have been used to covalently anchor inhibitor scaffolds and to increase
      their affinity to the protease. This review will examine the evolution of
      covalent inhibitors of the HCV NS3.4A protease from early aldehyde molecules to
      alpha-ketoamide inhibitors. Kinetic and structural studies of alpha-ketoacid and
      alpha-ketoamide inhibitors revealed an unusual mechanism of binding in the
      catalytic site. Optimization of alpha-ketoamide scaffolds by scientists at Vertex
      and Eli Lilly led to the discovery of VX-950, a novel, potent, selective
      inhibitor of HCV NS3.4A protease. VX-950 possesses excellent antiviral activity
      in both HCV replicon cells and human fetal hepatocytes infected with HCV-positive
      patient sera. In addition, VX-950 exhibits a favorable pharmacokinetic profile in
      several animal species and demonstrates potent inhibition of the HCV NS3.4A
      protease activity in a mouse model. In a recent phase 1b clinical trial, VX-950
      was able to rapidly reduce the plasma viral load of patients chronically infected
      with genotype 1 HCV by a mean approximately 3 log(10) in 2 days. The median viral
      load reduction was 4.4 log(10) for the best dose group after 14 days of dosing.
      The pre-clinical profile and early clinical data of VX-950 will be discussed in
      this review.

PMID- 16787302
TI  - Allosteric inhibition of the hepatitis C virus NS5B RNA dependent RNA polymerase.
AB  - The human and monetary costs of chronic hepatitis C and the complications arising
      from this disease emphasize the urgency to find a treatment for Hepatitis C Virus
      (HCV) infected patients. The current standard of treatment for patients
      chronically infected with HCV is combination therapy with pegylated interferon
      plus ribavirin. Recently, viral enzymes have become the target of efforts to
      develop small molecule inhibitors interfering with the essential steps in the
      life cycle of the virus. Amongst these enzymes the HCV-encoded NS5B RNA-dependent
      RNA polymerase (NS5B RdRp) is essential for viral replication and has been
      recognized as a prime target for therapeutic intervention. Several distinct
      classes of inhibitors of NS5B RdRp have been disclosed in the literature,
      including active site inhibitors such as nucleosides and pyrophosphate mimetics,
      as well as non-nucleoside inhibitors. The latter, based on the success of
      allosteric inhibitors in the treatment of HIV infection, have been developed into
      compounds which show activity in the subgenomic cell-culture assay of HCV
      replication. This review provides an account of the recent developments in this
      field.

PMID- 16787301
TI  - Nucleoside analog inhibitors of hepatitis C virus replication.
AB  - Of the 30 compounds currently marketed in the United States for treatment of
      viral infections, 15 are nucleoside analogs, demonstrating the utility of this
      class of compound as a source of antiviral drugs. The success of nucleoside
      analogs in treating other viral infections provides a compelling rationale for
      the significant effort that is currently being devoted to the discovery and
      development of nucleoside analogs to treat infection by hepatitis C virus (HCV)
      that may lead to improvements in response rates compared to currently available
      therapies. Several different approaches have been adopted to identify promising
      analogs, including the use of surrogate viruses in cell culture assays, screening
      in the cell-based bicistronic HCV replicon assay, and screening nucleoside
      triphosphates for the ability to inhibit the activity of the HCV RNA-dependent
      RNA polymerase in vitro. Several classes of ribonucleoside analogs with
      modifications of the ribose inhibit HCV replication. Nucleoside analogs
      incorporating a 2'-C-methyl modification are potent inhibitors in the replicon
      assay in the absence of cytotoxicity, and appear to exert their inhibition by
      acting as functional chain terminators of RNA synthesis. NM283, a prodrug of 2'-C
      methylcytidine, has entered clinical trials and demonstrated viral load
      reductions in subjects infected with genotype 1 HCV, a genotype known to be
      difficult to treat effectively with currently approved therapies. Overall,
      results to date offer encouragement that improved therapies to treat HCV
      infection including newly developed nucleoside analogs may become available
      within the next few years.

PMID- 16787303
TI  - Future promise of siRNA and other nucleic acid based therapeutics for the
      treatment of chronic HCV.
AB  - RNA interference (RNAi) is gaining favor as a potential therapeutic option for
      the treatment of Hepatitis C virus infections. RNAi, first discovered in plants,
      induces sequence specific degradation of messenger RNA following the introduction
      of short interference RNA (siRNA). RNAi is a natural defense mechanism used by
      plants to combat viral infections, and the discovery of RNAi activity in
      mammalian cells has prompted several drug companies to investigate and exploit
      RNAi based drugs as a potential therapy against HCV infections. A number of
      research groups have demonstrated that strong RNAi activity can be induced
      against HCV using synthetic siRNA duplexes as triggers, or by expressing short
      hairpin RNAs from plasmid or viral vectors. However, much work remains to improve
      delivery, maintain specificity and limit the development of virus resistance. HCV
      is capable of evading RNAi activity through the incorporation escape mutations
      within the siRNA target sequence, highlighting the importance of implementing
      strategies to limit the development of resistance. Other nucleic acid based
      therapies such as antisense oligonucleotides, RNA aptamers and ribozymes have
      also been considered for use as HCV therapeutics, and we will outline the
      potential opportunities and obstacles to their use as well as RNAi.

PMID- 16787304
TI  - Chronic hepatitis C in HIV-infected patients: those who more need therapy are
      those who respond less.
AB  - One third of HIV-infected individuals worldwide suffer from chronic hepatitis C
      virus (HCV) infection. Two main reasons justify considering HCV therapy as a
      priority in HIV-coinfected patients. First, these patients have more rapid liver
      disease progression, and second, they have a higher risk of developing
      hepatotoxicity following the initiation of antiretroviral therapy. Unfortunately,
      HCV therapy is associated with lower response rates and higher rate of side
      effects in HIV-coinfected patients. However, recent evidence suggests that when
      HCV therapy is administered adequately (to optimal candidates; using full doses
      of ribavirin; at least for 12 months irrespective of the HCV genotype; and with
      satisfactory drug adherence), treatment responses may not differ much from those
      seen in HCV-monoinfected individuals. Treatment should be considered up front in
      antiretroviral-naive subjects with stable HIV infection. In patients already on
      antiretroviral therapy, HCV therapy should not be administered before replacing
      didanosine by another antiretroviral, given the increased risk of mitochondrial
      toxicities. If possible, zidovudine should be avoided as well, given the high
      risk of anemia. The histological information provided by either non-invasive
      procedures (FibroScan, Fibro-test, etc.) or liver biopsy is useful but should not
      be considered as mandatory before prescribing HCV therapy. In summary, liver
      disease associated to HCV is a growing problem among HIV-positive individuals.
      The relatively low efficacy of current anti-HCV medications and their low
      tolerability clearly indicated the need for new drugs with more potent and direct
      antiviral activity against HCV.

PMID- 16787305
TI  - Synthesis of 12-deuterated and tritiated deoxoartemisinins.
AB  - The synthesis of C-12 deuterated and tritiated deoxoartemisinins is described.
      Tritiated deoxoartemisinin which could be incubated with the protein of
      Plasmodium falciparum for binding mechanism study was obtained by direct
      reduction of the carbonyl group of artemisinin using NaBT4 and BF3.Et2O in dried
      THF.

PMID- 16787306
TI  - Quantitative structure-activity relationship analysis of the cation permeability
      of the P2X2 channel.
AB  - The membrane-embedded, ligand-gated P2X glycoprotein receptor is a monovalent
      bivalent cation channel that is activated by physiological concentrations of
      extracellular ATP. A quantitative structure-activity relationship (QSAR) analysis
      was developed to model the cation permeability of the P2X2 channel and its
      mutants. As chemical properties, the helix-coil equilibrium constants and the
      distribution coefficients of the system octanol/water at pH 7.4 were applied and
      modified (sliding windows) according to Eroshkin et al. (Comput. Appl. Biosci.,
      1995, 11, 49-44). The results were visualized by a dimeric P2X2 channel
      construct. The results support the hypothesis that residues which put into the
      cavity and contribute to hydrogen bonding forces are involved to a control of the
      transport of hydrated cations through the P2X2 channel. The model may be useful
      to develop P2X2 receptor antagonists.

PMID- 16787308
TI  - Recent advances in the new generation taxane anticancer agents.
AB  - Recent advances in the design and preclinical evaluations of promising new
      generation taxane anticancer agents are reviewed in this article. Paclitaxel and
      docetaxel are two of the most important anticancer drugs today. However, recent
      reports have shown that treatment with these drugs often encounters undesirable
      side effects as well as drug resistance. Therefore, it is important to develop
      new taxane anticancer agents with fewer side effects, superior pharmacological
      properties, and improved activity against drug-resistant human cancers. Structure
      activity relationship (SAR) studies led to the discovery of a series of highly
      active second-generation taxanes. One of them, "Ortataxel" (SB-T-101131, IDN5109,
      BAY59-8862), exhibits excellent activity against a variety of drug-sensitive and
      drug-resistant cancer cell lines, as well as human tumor xenografts in mice. It
      is orally active and is currently in phase II clinical trials. Photoaffinity
      labeling of microtubules and P-glycoprotein using photoreactive radiolabeled
      taxoids has disclosed the drug-binding domain of tubulin as well as Pgp. Together
      with information on microtubule-bound fluorine-labeled taxoids obtained by solid
      state NMR studies, the bioactive conformation of paclitaxel and taxoids appears
      to emerge. Novel taxane-monoclonal antibody (mAb) immunoconjugates, have shown
      highly promising results for the tumor-specific delivery and release of an
      extremely cytotoxic, second-generation taxane. Also, another novel series of
      second generation taxanes conjugated with n-3 polyunsaturated fatty acids, e.g.
      decosahexaenoic acid (DHA), has exhibited impressive antitumor activity with
      minimum general toxicity against the highly drug-resistant DLD-1 human colon
      cancer xenografts in SCID mice.

PMID- 16787307
TI  - 3-(1H-pyrrol-2-yl)-2-oxazolidinones as novel monoamine oxidase type A inhibitors.
AB  - A novel series of 5-substituted-3-(1H-pyrrol-2-yl)-2-oxazolidinones 2a-s has been
      described as pyrrole analogues of toloxatone and befloxatone, two phenyl
      oxazolidinones active as anti-MAO agents and used in antidepressant therapy.
      Tested against MAO-A and MAO-B enzymes, the majority of 2a-s show highly potent
      inhibitory effect against the A isoform of the enzyme, with Ki values in the
      range 0.52-0.004 microM, whilst their anti-MAO-B activity is considerably lower
      (Ki = >100-0.5 microM). Structurally, 2a-s differs for the substituent inserted
      at the C5 position of the 2-oxazolidinone ring (hydroxymethyl (2a-d),
      methoxymethyl (2e-h), azidomethyl (2i-l), methylaminomethyl (2m-p), and
      aminomethyl (2q-s)), and the size of the alkyl chain at the pyrrole N1 position
      (methyl, ethyl, allyl, or benzyl). As a rule, apart from the C5 substitution, the
      bulkier is the alkyl group at the pyrrole-N1, the lower is the anti-MAO-A
      activity of the compounds, being the N1-methyl derivatives 2a, 2e, 2i, and 2q
      among the most potent (K(iMAO-A) = 0.087-0.004 microM) and A-selective (A
      selectivity ratio: >11,111-41) compounds in this series. Exceptions are
      represented by the N1-benzyl derivative 2d (K(iMAO-A) = 0.009 microM) and the N1
      allylpyrrole 2o (K(iMAO-A) = 0.04 microM). In comparison with the reference
      drugs, these highly active derivatives are more potent than toloxatone, slightly
      less potent than befloxatone, and several times more A-selective than both the
      references. Such results indicate that 2a-s may represent a new promising series
      of antidepressant agents.

PMID- 16787309
TI  - A pyridinium-substituted analog of the TRH-like tripeptide pGlu-Glu-Pro-NH2 and
      its prodrugs as central nervous system agents.
AB  - A metabolically stable and centrally acting analog of pGlu-Glu-Pro-NH2
      ([Glu2]TRH, a tripeptide structurally related to TRH (thyrotropin-releasing
      hormone)) was designed by replacing the amino-terminal pyroglutamyl residue with
      a pyridinium moiety. The analeptic action of the analog was used to optimize the
      efficacy of this novel CNS agent when administered intravenously in its CNS
      permeable prodrug forms obtained via the reduction of the pyridinium moiety to
      the nonionic dihydropyridine and esterifying the central Glu with various
      alcohols. The maximum effect in antagonizing pentobarbital-induced narcosis in
      mice was achieved with the hexyl ester that was used subsequently for a
      comparative evaluation with a prodrug of the parent neuropeptide in the Porsolt
      swim test as a paradigm for antidepressant effect. The novel analog maintained
      its antidepressant potency but showed reduced analeptic action compared to
      [Glu2]TRH; thus, an increase in the selectivity of CNS-action was obtained by the
      incorporation of the pyridinium moiety.

PMID- 16787310
TI  - Reversible regulation of chymotrypsin activity using negatively charged gold
      nanoparticles featuring malonic acid termini.
AB  - Negatively charged gold nanoparticles featuring 2-(10-mercapto-decyl)-malonic
      acid were synthesized using the Murray place-displacement reaction. These water
      soluble malonate gold mixed monolayer protected clusters (MMPCs) effectively bind
      and inhibit chymotrypsin based on complementary electrostatic surface
      recognition. The effect of increasing ionic strength on inhibition was also
      studied. It was observed that addition of high ionic strength solutions to
      protein-nanoparticle complexes show almost complete restoration of protein
      activity. The conformational change of chymotrypsin upon binding to the MMPC was
      investigated using fluorescence spectrometry and circular dichroism, thus
      correlating structural changes with enzyme activity.

PMID- 16787311
TI  - Growth inhibition of drug-resistant species of Plasmodium falciparum by domain
      structured N1,N2-derivatized hydrazines: denticity effects, redox switches, and
      reductant-driven redox-cycling.
AB  - Six analogs of bidentate 1-[pyridoxylidene]-2-phenyl]hydrazine, twelve analogs of
      N2O-tridentate 1-[pyridoxylidene]-2-[heteroaryl]hydrazine, and four O2N
      tridentate analogs of 1-[pyridoxylidene]-2-[heteroaroyl] hydrazines were
      synthesized and characterized. Their solutions in water and DMSO were assayed in
      vitro for activity against a chloroquine-resistant species of P. falciparum
      obtained from Hadassah Hospital Blood Bank in Jerusalem. The O2N-tridentate group
      was essentially inactive, whereas the bidentate group, with N and O liganding
      atoms, exhibited slight activity against late-stage trophozoites and schizonts of
      P. falciparum. The N2O-tridentate group, by contrast, was remarkably active
      against resistant P. falciparum, highlighting the importance of the Denticity
      Effect in this system. It is assumed that the pyridoxal-based chelator acts as an
      iron redox mediator, controlling the first coordination sphere and, therefore,
      the immediate chemical environment of the iron. Chelation of iron-(II) presumably
      facilitates its oxidation..The Fe(II) --> Fe(III) intra-electron transfer, may be
      viewed as a switch ("redox switch"), controlling the thermodynamic stability and
      kinetic lability of the coordination shell. The redox-switch is accompanied by
      the appearance of a carbon-based Fe-(III)-chelate radical, capable of donating
      its free electron to the parasite-DNA, thus causing death. The antimalarial N2O
      tridentate Fe(III)-chelates appear to be prone to redox-switch, and tend to be
      converted into their Fe(II) species, whereas the inactive O2N-tridentate analogs
      apparently cannot do so.

PMID- 16787312
TI  - Selection of molecular descriptors with artificial intelligence for the
      understanding of HIV-1 protease peptidomimetic inhibitors-activity.
AB  - Quantitative Structure Activity Relationship (QSAR) techniques are used routinely
      by computational chemists in drug discovery and development to analyze datasets
      of compounds. Quantitative numerical methods like Partial Least Squares (PLS) and
      Artificial Neural Networks (ANN) have been used on QSAR to establish correlations
      between molecular properties and bioactivity. However, ANN may be advantageous
      over PLS because it considers the interrelations of the modeled variables. This
      study focused on the HIV-1 Protease (HIV-1 Pr) inhibitors belonging to the
      peptidomimetic class of compounds. The main objective was to select molecular
      descriptors with the best predictive value for antiviral potency (Ki). PLS and
      ANN were used to predict Ki activity of HIV-1 Pr inhibitors and the results were
      compared. To address the issue of dimensionality reduction, Genetic Algorithms
      (GA) were used for variable selection and their performance was compared against
      that of ANN. Finally, the structure of the optimum ANN achieving the highest
      Pearson's-R coefficient was determined. On the basis of Pearson's-R, PLS and ANN
      were compared to determine which exhibits maximum performance. Training and
      validation of models was performed on 15 random split sets of the master dataset
      consisted of 231 compounds. For each compound 192 molecular descriptors were
      considered. The molecular structure and constant of inhibition (Ki) were selected
      from the NIAID database. Study findings suggested that non-covalent interactions
      such as hydrophobicity, shape and hydrogen bonding describe well the antiviral
      activity of the HIV-1 Pr compounds. The significance of lipophilicity and
      relationship to HIV-1 associated hyperlipidemia and lipodystrophy syndrome
      warrant further investigation.

PMID- 16787313
TI  - Immunohistochemical and serological 90K/Mac-2BP detection in hepatocellular
      carcinoma patients: different behaviour of two monoclonal antibodies.
AB  - To clarify the biological role of the 90K/Mac-2BP glycoprotein, we evaluated the
      ability of two MAbs SP-2 and 1A4.22, to reveal this glycoprotein in both serum
      and tissue from hepatocellular carcinoma (HCC) patients. Tissue expression of 90K
      was detected by the immunohistochemical method in 20 HCC patients, while the 90K
      serum level was assessed by the ELISA assay in 13 HCC patients. MAb SP-2 was
      reactive only in serum, with a mean value of 12.8+/- 6.7 microg/ml . On the
      contrary, MAb 1A4.22 revealed immunoreactivity both in 92% of sera and in 60% of
      neoplastic samples. Positive staining was seen only in the epithelial cells and
      was cytoplasmic and granular in all instances. The mean 90K serum level assayed
      with MAb 1A4.22 was 29.4 +/- 13.7 microg/ml. Patients with a 90K serum level <or=
      30 microg/ml had positive tissue samples in 71% of cases versus 20% of patients
      with a serum level > 30 microg/ml. Moreover, a possible poor prognostic role was
      observed for negative 90K in tissue. Our results suggest that only MAb 1A4.22
      could demonstrate 90K glycoprotein expression in paraffin-embedded tissue and
      that this MAb could have a diagnostic and prognostic role in both sera and
      tissues from HCC patients.

PMID- 16787314
TI  - Mechanistic studies of inactivation of glutathione S-transferase Pi isozyme by a
      haloenol lactone derivative.
AB  - Cancer chemotherapy often fails due to acquired drug resistance. One of the most
      critical biochemical changes observed in drug-resistant tumor cells is over
      expression of glutathione S-transferase Pi isozyme (GSTP1). Glutathione S
      transferase inhibitors have been used as potentiating agents of chemotherapeutic
      drugs. Earlier we reported haloenol lactone 1 as a site-directed GSTP1
      inactivator. We proposed that enzymatic hydrolysis of the haloenol lactone may be
      the initial step of GSTP1 chemical modification, resulting in the inactivation of
      the enzyme. Enzyme inactivation is initiated through addition of Cys-47 to the
      lactone ring, which is opened in the process to form an alpha-bromoketone adduct.
      The acidity of Cys-47 confers good leaving group properties, and rapid hydrolysis
      occurs to generate an alpha-bromoketoacid intermediate. The reaction may proceed
      via alkylation of the transient thioester to form a six-membered ring
      episulfonium ion intermediate which would be yet more reactive toward hydrolysis,
      with either process leading to the observed mass increase of 230 Da. To probe the
      importance of the bromine of the lactone in GST inactivation, we designed and
      synthesized compound 2. Unlike lactone 1, lactone 2 did not show time-dependent
      inhibitory effect on GSTP1. Incubation of compounds 1 and 2 with excess of N
      acetyl cysteine produced the corresponding di-N-acetyl cysteine conjugate and
      mono-N-acetyl cysteine conjugate, respectively. To probe the role of Cys-47 in
      the inactivation of GSTP1 by compound 1, we prepared mutant C47A GSTP1. The
      mutant GSTP1 still showed good activity toward CDNB, but it lost susceptibility
      to the inactivation by compound 1. In addition, LC-MS/MS technique allowed us to
      identify the modified Cys-47 after the enzyme was exposed to compound 1.

PMID- 16787315
TI  - DNA and RNA aptamers as modulators of protein function.
AB  - The SELEX technique (systematic evolution of ligands by exponential enrichment)
      is a combinatorial library approach in which DNA or RNA molecules are selected by
      their ability to bind their protein targets with high affinity and specificity.
      The isolated molecules are referred to as aptamers (from aptus = Latin "to fit").
      First, RNA and DNA aptamers were identified that bind to proteins naturally
      interacting with nucleic acids, or to small organic molecules such as ATP. In the
      following years, the use of the SELEX technique was extended to isolate
      oligonucleotide ligands for a wide range of proteins of importance for therapy,
      and diagnostics. Since these RNA and DNA molecules bind their targets with
      similar affinities as antibodies, and are able to distinguish between isotypes of
      an enzyme, aptamers have been also called synthetic antibodies. Recently, the use
      of in vitro selection methods to isolate protein inhibitors has been extended to
      complex targets, such as receptors that are only functional in their membrane
      bound form, cells, and trypanosomes. RNA aptamers have been expressed in living
      cells where they inhibit a protein implicated in intracellular signal
      transduction. The utility of aptamers for in vivo experiments, and diagnostic and
      therapeutic purposes, is considerably enhanced by introducing chemical
      modifications into the oligonucleotides to provide resistance against enzymatic
      degradation in body fluids. Recently, such inhibitors have been evolved for a
      great variety of targets, including receptors, growth factors, and adhesion
      molecules implicated in disease. Furthermore, some results were already obtained
      in animal models and clinical trials.

PMID- 16787317
TI  - Effects of introducing silicon isosteres in COX-2 inhibitors: a preliminary in
      silico evaluation.
AB  - Since the discovery that the anti-inflammatory effects of cyclooxygenase
      (prostaglandin endoperoxide H(2) synthetase; COX) inhibitors were dependent on
      their selectivity for the inducible COX-2 isoform over the constitutive COX-1,
      many efforts have been devoted towards the design of compounds displaying
      improved COX-2 selectivity. Classical bioisosteres such as CH-CF and CH(2)-S/O
      substitutions have been extensively used in the design of the classical COX-2
      inhibitors, although silicon isosteres have been so far overlooked. The
      replacement of a carbon by a silicon atom can have beneficial effects in this
      particular family of compounds, because the increased bond lengths and altered
      bond angles brought by the sila-substitution might modify their binding mode to
      the COX enzymes. In order to evaluate such possible benefits, several well
      characterized model inhibitors were selected and docked in the murine COX-2 and
      COX-1 binding sites. The binding energies for the interaction of each model
      compound with the respective isoenzymes were derived from the docking data. As in
      previous publications, these were found to correlate closely (r(2) = 0.66 and
      0.75 for COX-2 and COX-1, respectively) with experimental inhibitory activities
      towards the recombinant enzymes gathered from the literature. These relationships
      allowed the prediction of the inhibitors activity towards both enzyme isoforms,
      which further permitted the prediction of their selectivity for COX-2 with an
      acceptable accuracy (cross-validated squared correlation coefficient q(2) =
      0.64). These model compounds were theoretically modified by substituting selected
      carbon atoms by an sp(3) silicon, and further docked in both COX-2 and COX-1
      binding sites in order to derive their predicted inhibitory activity for both
      isoforms. Except in a few cases, the sila-substitution did not significantly
      increase the inhibitory activity towards COX-2. In most cases however, it
      produced a significant decrease in the inhibitory activity towards COX-1. These
      results indicate that isosteric sila-substitutions could be of value in the
      design of COX inhibitors with improved selectivity for COX-2.

PMID- 16787316
TI  - Application of bioinformatics in search for cleavable peptides of SARS-CoV M(pro)
      and chemical modification of octapeptides.
AB  - According to the "distorted key" theory as elaborated in a review article years
      ago (Chou, K.C.: Analytical Biochemistry, 1996, 233, 1-14), the knowledge of the
      cleavable peptides by SARS-CoV M(pro) (severe acute respiratory syndrome
      coronavirus main proteinase) can provide very useful insights on developing drugs
      against SARS. In view of this, the softwares, ZCURVE_CoV 1.0 and ZCURVE_CoV 2.0
      (http://tubic.tju.edu.cn/sars/), developed recently for SARS-Coronavirus are used
      to analyze the 36 complete SARS-Coronavirus RNA sequences in the gene bank NCBI
      (http://www.ncbi.nlm.nih.gov/) from different sources for protein coding genes,
      and to search for the cleavage sites of SARS-CoV M(pro) in polyproteins pp1a and
      pp1ab. A total of 396 cleavage points are found in the 36 SARS-Coronavirus and 11
      cleavable octapeptides abstracted from the 396 cleavage sites. The statistical
      distributions of amino acids for the cleavable octapeptides at the subsites R4,
      R3, R2, R1, R1', R2', R3' and R4' are calculated. The cleavage-specific positions
      are on R2, R1 and R1', and the positions R3 and R4 are featured by some certain
      specificity for SARS-CoV M(pro). The structural characters of amino acid residues
      around the cleavage-specific positions are discussed. Two most promising
      octapeptides, i.e., NH(2)-ATLQ downward arrowAIAS-COOH and NH(2)-ATLQ downward
      arrowAENV-COOH, are selected to be the candidates for chemical modification,
      converting into the inhibitors of SARS-CoV M(pro). A possible strategy to convert
      a cleavable octapeptide by SARS enzyme into a drug candidate against SARS is
      elucidated.

PMID- 16787318
TI  - Investigation of bioisosteric effects on the interaction of substrates/
      inhibitors with the methionyl-tRNA synthetase from Escherichia coli.
AB  - Aminoacyl-tRNA synthetases catalyze the stepwise coupling of specific amino acid
      substrates to their cognate tRNAs. The first intermediate formed in this process
      is the aminoacyl-adenylate, which then subsequently reacts with the 3'-terminus
      of the cognate tRNA to transfer the amino acid to the tRNA. This overall reaction
      is critical for protein biosynthesis and is quintessential to the viability of
      all organisms. Therefore, the selective inhibition of bacterial amino acid-tRNA
      synthetases is the focus of intense current interest for the development of novel
      antibacterial agents. In order to elucidate some of the critical factors involved
      in recognition and binding of potential inhibitors to these bacterial systems,
      the current report has focused on the methionyl-tRNA synthetase from Escherichia
      coli. This enzyme has been studied with two sets of bioisosteric replacements in
      the methionine and methionyl-adenylate structures. Replacements of the carboxyl
      group of methionine with the phosphinic and phosphonic acid moieties were used to
      probe the effects of including potential transition state analogs on enzyme
      inhibition. The contributions of the aminoacyl-adenylate structure and the effect
      that fluorination has on inhibitory activity were investigated utilizing 5'-O-[(L
      methionyl)-sulfamoyl]adenosine and 5'-O-[(S-trifluoromethyl-L-homocysteinyl)
      sulfamoyl]adenosine. The K(i) values for these compounds were determined to be
      0.4 mM, 1.2 mM, 0.25 nM and 2.4 nM respectively. A discussion of this data in
      relation to structural information provided by the recent determination of the
      three-dimensional structures of the E. coli enzyme with several of these
      compounds is presented.

PMID- 16787319
TI  - Variously substituted (phosphonoacetamido)oxy analogues of geranylgeranyl
      diphosphate (GGdP) as GGdP-transferase (GGTase) inhibitors and antiproliferative
      agents.
AB  - Aberrant signalling through the pathways of small GTP-binding proteins, belonging
      to the Ras superfamily (Ras, Rho, Rac, Cdc42 etc.), occurs in several types of
      cancer, where mutated Ras accumulates in its GTP-bound active form and causes
      uncontrolled cell proliferation. For these reasons, molecules able to target the
      Ras pathway in any of its stages are potentially useful in anti-cancer therapies.
      Inhibition of farnesyl-protein transferase (FTase), the enzyme that post
      translationally activates Ras, has been pursued for the obvious role of the Ras
      oncoprotein in human malignancies. It was later found that some mutated forms of
      Ras (K- and N-Ras) can also be geranylgeranylated by geranylgeranyl-protein
      transferase (GGTase) when FTase is blocked, circumventing the antiproliferative
      effects of FTase inhibitors. Therefore, a new task has been the search for new
      GGTase inhibitors, which can also interfere on cell proliferation by blocking the
      isoprenylation of other Ras superfamily proteins (i.e. Rho, Rac, Cdc42) involved
      in the regulation of cell cycle progression. We have recently described a series
      of phosphonoacetamido- and phosphonoacetamidoxy-stable analogues of
      geranylgeranyl-diphosphate (GGdP) possessing good GGTase inhibitory properties
      and, some of them, also remarkable GGTase/FTase selectivity levels. We have now
      extended this series to a larger number of variously substituted
      phosphonoacetamidoxy-analogues of GGdP in order to establish the effect on GGTase
      inhibitory activity and selectivity due to the presence of different substituents
      in the polar portion of these GGdP mimics. We have also measured the cytotoxicity
      of these compounds on tumour cell lines with the aim of evaluating their
      potential anti-proliferative effects.

PMID- 16787320
TI  - Synthesis and biological evaluation of 2-, 3-, and 4-acylaminocinnamyl-N
      hydroxyamides as novel synthetic HDAC inhibitors.
AB  - A new series of 2-, 3-, and 4-acylaminocinnamyl-N-hydroxyamides 1-3 have been
      prepared, and their anti-HDAC (against maize HD2, HD1-B, and HD1-A enzymes)
      activities have been assessed. Cinnamyl-hydroxyamides bearing acylamino
      substituents at the C2 position of the benzene ring (compounds 1a-g) showed very
      low HDAC inhibiting activities, with IC(50) values in the high micromolar range.
      By shifting the same acylamino groups from C2 to C3 (compounds 2a-g) as well as
      C4 (compounds 3a-f) position of the benzene ring, a number of highly potent HDAC
      inhibitors have been obtained. In the anti-HD2 assay 3c (IC(50) = 11 nM) was the
      most potent compound, being >11600-, 4.5-, and 10-fold more potent than sodium
      valproate, SAHA, and HC-toxin, respectively, and showing the same activity as
      trapoxin. HD1-B and HD1-A assays have been performed to screen the inhibitory
      action of 1-3 against mammalian class I (HD1-B) and class II (HD1-A) HDAC
      homologous enzymes. From the corresponding IC(50) data, a selectivity ratio has
      been calculated. In general, compounds 1-3 showed no or little selectivity
      towards the class II homologue HD1-A, the most selective being 2a with class II
      selectivity ratio = 4.3. About the inhibitory potency, the 4-(2
      naphthoylamino)cinnamyl-N-hydroxyamide 3f showed the highest inhibiting effect
      against the two enzymes (IC(50-HD1-B) = 36 nM; IC(50-HD1-A) = 42 nM). Selected 2
      and 3 compounds will be evaluated to determine their antiproliferative and cyto
      differentiating activities on HL-60 cells.

PMID- 16787322
TI  - Discovery of HIV-1 integrase inhibitors through a novel combination of ligand and
      structure-based drug design.
AB  - Over the past 10 years, classical computer-aided molecular design methods have
      not been frequently applied for the discovery of novel HIV-1 integrase (IN)
      inhibitors, due to the intrinsic challenges that this enzyme presents. Therefore,
      a novel approach that combines the chemical information of known integrase
      inhibitors with the enzyme's detailed 3D structure in a stepwise fashion is
      proposed: (I) use of a pharmacophore model (PM), which takes into account in a
      weighted fashion the chemical features of known ligands, in analogous manner to
      the to search the Maybridge and the NCI 3D databases; (II) drug-likeness
      optimization; (III) virtual high-throughput screening of the hits matching the PM
      query against 1QS4 wild-type IN structure using different Docking/Scoring
      combinations; (IV) visual inspection and selection of the hits in function of:
      binding free energies; binding mode type within the active site; retrieval among
      the best 20% hits in more than 6 Docking/Scoring protocols at the same time. This
      approach aims at a rational selection of new potential HIV-1 integrase
      inhibitors.

PMID- 16787321
TI  - Synthesis and evaluation of a novel gene reporter molecule: detection of beta
      galactosidase activity using 19F NMR of a fluorinated vitamin B6 conjugate+.
AB  - Gene therapy has emerged as a promising strategy for treatment of various
      diseases. However, widespread implementation is hampered by difficulties in
      assessing the success of transfection, in particular, the spatial extent of
      expression in the target tissue and the longevity of expression. Thus, the
      development of non-invasive reporter techniques based on appropriate molecules
      and imaging modalities may help to assay gene expression. We now report the
      design, synthesis and evaluation of a novel in vivo gene transfection reporter
      molecule 3-O-(beta-D-galactopyranosyl)-6-fluoropyridoxol (GFPOL) using
      fluorinated vitamin B(6) as the (19)F NMR sensitive aglycone. GFPOL exhibits the
      following strengths as an in vivo (19)F NMR gene expression reporter: (a) large
      chemical shift response to enzyme cleavage (Deltadelta=8.00 ppm); (b) minimal
      toxicity for substrate or aglycone; (c) good water solubility; (d) good blood
      stability; (e) pH responsiveness of aglycone.

PMID- 16787324
TI  - Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase.
AB  - The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum
      (St. John's wort), was recently identified as potent and direct inhibitor of 5
      lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory
      leukotrienes. In this study, naturally occurring analogues of hyperforin,
      isolated from H. perforatum, as well as a series of synthetic derivatives
      obtained by chemical modification of hyperforin by acylation, alkylation or
      oxidation, were analysed for the inhibition of 5-LO. The efficacies of these
      compounds were evaluated in intact human polymorphonuclear leukocytes, but also
      the inhibitory effects on isolated recombinant human 5-LO were investigated. Our
      data show that some of the oxidised hyperforin derivatives possess even improved
      efficacy, whereas alkylation and acylation have detrimental effects.

PMID- 16787323
TI  - Aminopyrimidinimino isatin analogues: design and synthesis of novel non-
      nucleoside HIV-1 reverse transcriptase inhibitors with broad-spectrum anti
      microbial properties.
AB  - HIV is the most significant risk factor for many opportunistic infections like
      tuberculosis, bacterial infections etc. In this paper, we designed
      aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse
      transcriptase inhibitor with broad-spectrum chemotherapeutic properties for the
      effective treatment of AIDS and AIDS-related opportunistic infections. Compound 1
      ethyl-6-fluoro-1,4-dihydro-4-oxo-7[[N(4)-[3'-(4'-amino-5'-chloroben-zylpyrimidin
      2'-yl)imino-1'-(5-methylisatinyl)] methyl]N(1)-piperazinyl]-3-quinoline
      carboxylic acid (10) emerged as the most potent broad-spectrum chemotherapeutic
      agent active against HIV-1 replication (EC(50): 9.4 microg /ml), M. tuberculosis
      (MIC: 3.13 microg /ml) and various pathogenic bacteria (MIC's: 1.22 microg /ml).

PMID- 16787325
TI  - Protein phosphorylation and signal transduction modulation: chemistry
      perspectives for small-molecule drug discovery.
AB  - Protein phosphorylation has been exploited by Nature in profound ways to control
      various aspects of cell proliferation, differentiation, metabolism, survival,
      motility and gene transcription. Cellular signal transduction pathways involve
      protein kinases, protein phosphatases, and phosphoprotein-interacting domain
      (e.g., SH2, PTB, WW, FHA, 14-3-3) containing cellular proteins to provide
      multidimensional, dynamic and reversible regulation of many biological
      activities. Knowledge of cellular signal transduction pathways has led to the
      identification of promising therapeutic targets amongst these superfamilies of
      enzymes and adapter proteins which have been linked to various cancers as well as
      inflammatory, immune, metabolic and bone diseases. This review focuses on protein
      kinase, protein phosphatase and phosphoprotein-interacting cellular protein
      therapeutic targets with an emphasis on small-molecule drug discovery from a
      chemistry perspective. Noteworthy studies related to molecular genetics, signal
      transduction pathways, structural biology, and drug design for several of these
      therapeutic targets are highlighted. Some exemplary proof-of-concept lead
      compounds, clinical candidates and/or breakthrough medicines are further detailed
      to illustrate achievements as well as challenges in the generation, optimization
      and development of small-molecule inhibitors of protein kinases, protein
      phosphatases or phosphoprotein-interacting domain containing cellular proteins.

PMID- 16787326
TI  - Assessment in vitro of a novel therapeutic strategy for glioma, combining herpes
      simplex virus HSV1716-mediated oncolysis with gene transfer and targeted
      radiotherapy.
AB  - Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only
      in dividing cells and have shown potential for the treatment of malignant
      disease, including glioma. Phase I trials have demonstrated the safety of these
      viruses in various clinical settings but it is envisaged that for full efficacy
      they will be used in combination with other therapeutic modalities. To enhance
      virus-induced tumour cytotoxicity, we have engineered an ICP34.5 null mutant
      (HSV1716) of HSV1 which expresses the noradrenaline transporter gene (NAT). This
      virus is designated HSV1716/NAT. We have shown previously that introduction of
      the NAT gene into a range of tumour cells, via plasmid-mediated transfection,
      conferred the capacity for active uptake of the radiopharmaceutical [131I]MIBG
      and resulted in dose-dependent toxicity. In this study, combination therapy
      utilising HSV1716/NAT and [131I]MIBG was assessed in vitro by the MTT assay. We
      demonstrate that the NAT gene, introduced by HSV1716/NAT into cultured glioma
      cells, was expressed 1 h after viral infection, enabling active uptake of
      [131I]MIBG. The combination of viral oncolysis and induced radiopharmaceutical
      uptake resulted in significantly enhanced cytotoxicity compared to either agent
      alone and the response was dose- and time-dependent. These studies show that the
      combination of oncolytic HSV therapy with targeted radiotherapy has the potential
      for effective tumour cell kill and warrants further investigation as a treatment
      for malignant glioma.

PMID- 16787327
TI  - Interaction field based and hologram based QSAR analysis of propafenone-type
      modulators of multidrug resistance.
AB  - Overexpression of membrane bound, ATP-dependent transport proteins is one of the
      predominant mechanisms leading to multiple drug resistance in tumor therapy as
      well as in the treatment of bacterial and fungal infections. In tumor therapy, P
      glycoprotein (P-gp, ABCB1) is responsible for transport of a wide variety of
      natural product toxins out of tumor cells leading to decreased accumulation of
      cytotoxic drugs within the cells. Inhibition of P-gp thus gives rise to a
      resensitization of multidrug resistant tumor cells and represents a versatile
      approach for modulation of multidrug resistance. Within this paper, a set of
      propafenone-type inhibitors of P-gp were analyzed using both interaction field
      based methods such as CoMFA and CoMSIA and Hologram QSAR. With both methods,
      highly predictive models with q2-values>0.65 were obtained. Models using logP as
      additional descriptor generally yielded higher predictive power. On basis of
      unfavorable steric and favorable electrostatic and hydrophobic interaction
      fields, these models were able to explain all outlayers identified in previous
      Hansch-analyses. For HQSAR analysis, models with q2-values up to 0.72 were
      obtained. Positive influences were found for electron donating groups on the
      aromatic systems. Highly negative influences were found for diphenylalkylamine
      substituents, which is a further hint for steric hindrance. The models with
      highest predictive power were used for screening of a small virtual library.
      Synthesis and pharmacological testing of a sub set of this library showed that
      the external predictivity of the HQSAR models generally is lower than the
      internal one.

PMID- 16787328
TI  - Comparison of (+)- and (-)-hemipalmitoylcarnitinium as inhibitors of hepatic
      mitochondrial carnitine palmitoyltransferases in diabetic rats.
AB  - The syntheses of (R)- and (S)-norcarnitine ethyl esters are described starting
      with an optimized, chiral chemical reduction of ethyl 4-chloroacetoacetate
      followed by azide substitution, reduction, and dimethylation. The reaction of (R)
      and (S)-norcarnitine ethyl esters with 1-bromoheptadecan-2-one gives (+)- and (
      )-6-[(methoxycarbonyl)methyl]-2-pentadecyl-4,4-dimethylmorpholinium bromide,
      respectively, which hydrolyzes to (+)- and (-)-6-(carboxylatomethyl)-2-pentadecyl
      4,4-dimethylmorpholinium (hemipalmitoylcarnitinium, (+)- and (-)-HPC),
      respectively, upon treatment with a hydroxide resin. (+)- and (-)-HPC are
      reversible active-site directed inhibitors of hepatic mitochondrial CPTs. Both
      stereoisomers inhibit CPT I and CPT II in control and streptozotocin diabetic rat
      to the same extent (Imax=100%). Using intact mitochondria (CPT I), I50values for
      (-)-HPC and (+)-HPC were 15.5 microM and 47.5 microM, respectively. The I50
      values for CPT II were 6.7 microM and 38.5 microM for (-)-HPC and (+)-HPC,
      respectively. The mode of inhibition was uncompetitive for CPT I with respect to
      acyl-CoA. The apparent K(i) for (-)-HPC is about 5 microM. These data suggest
      that (-)-HPC may be useful for further evaluation as an antidiabetic agent.

PMID- 16787329
TI  - Free energy perturbation calculations on glucosidase-inhibitor complexes.
AB  - Free energy perturbation studies have been performed on Glucoamylase II (471)
      from Aspergillus awamori var. X100 complexed with three different inhibitors:
      (+)lentiginosine, (+)(1S,2S,7R,8aS) 1,2,7-trihydroxyindolizidine,
      (+)(1S,2S,7S,8aS) 1,2,7-trihydroxyindolizidine and the inactive compound
      (+)(1S,7R,8aS)-1,7-dihydroxyindolizidine. Molecular dynamic simulations were
      carried out using a recently developed procedure for fast Free Energy
      Perturbation calculations. In this procedure only a sphere of 1.8 nm around the
      central atom of the inhibitor is considered in the calculations. Crystallographic
      restraints are applied over this reduced system using a generated electron
      density map. The obtained values for the free energy differences agree with
      experimental data showing the importance of fast calculations in drug design even
      when the crystallographic structure of the complex is not available. As the
      method uses only the crystallographic structure of the receptor, it is possible
      to test the possible efficiency of even still not synthesised ligands, making the
      pre-selection of compounds much easy and faster.

PMID- 16787330
TI  - Statin attenuates high glucose-induced and angiotensin II-induced MAP kinase
      activity through inhibition of NAD(P)H oxidase activity in cultured mesangial
      cells.
AB  - An increased oxidative stress may contribute to the development of diabetic
      nephropathy. We have recently reported that high glucose level stimulated
      superoxide production through protein kinase C (PKC)-dependent activation of
      NAD(P)H oxidase in cultured vascular cells. Here we show that 3-hydroxy-3
      methylglutaryl CoA reductase inhibitor (statin) attenuates both high glucose
      level-induced and angiotensin II (Ang II)-induced activation of p42/44 mitogen
      activated kinase (MAP kinase) in cultured human mesangial cells through
      inhibition of NAD(P)H oxidase activity. The intracellular oxidative stress in
      cultured mesangial cells was evaluated by electron spin resonance (ESR)
      measurement. MAP kinase activity was evaluated by western blot analysis using
      anti phospho-specific MAP kinase antibody and anti-ERK-1 antibody. Exposure of
      the cells to high glucose level (450 mg/dl) for 72 hrs significantly increased
      MAP kinase activity as compared to normal glucose level (100 mg/dl). This
      increase was completely blocked by the treatment of pitavastatin (5x10(-7) M) as
      well as a NAD(P)H oxidase inhibitor (diphenylene iodonium, 10(-5) M) in parallel
      with the attenuation of oxidative stress. Ang II-induced activation of MAP kinase
      was also completely blocked by pitavastatin as well as a diphenylene iodonium in
      parallel with the attenuation of oxidative stress. In conclusion, pitavastatin
      attenuated high glucose-induced and Ang II- induced MAP kinase activity in
      mesangial cells through inhibition of NAD(P)H oxidase. Thus, statins may have a
      potential as a therapeutic tool for early diabetic nephropathy.

PMID- 16787331
TI  - ICG-001, a novel small molecule regulator of TCF/beta-catenin transcription.
AB  - Inherited and somatic mutations in the APC gene, a human tumor-suppressor, occur
      in a large percentage of colon cancers, leading to elevated levels of nuclear
      beta-Catenin, and to activation of TCF/beta-Catenin-responsive genes including
      cyclin D1 and c-myc. To identify small molecule antagonists of this pathway, we
      screened transformed colorectal cells with a secondary structure-templated
      chemical library, in search of compounds that attenuated a TCF/beta-Catenin
      responsive reporter gene. From this library we selected ICG-001 (IC50=3 microM)
      as a lead compound. Design and synthesis of the chemical library and some
      preliminary biological evaluation is described.

PMID- 16787332
TI  - Enantioselective synthesis and preliminary pharmacological evaluation of the
      enantiomers of unifiram (DM232), a potent cognition-enhancing agent.
AB  - The enantiomers of the potent cognition-enhancer DM232 ((1), unifiram) and of its
      isopropylsulfonyl analog (2), which is endowed with amnesic properties, have been
      synthesized using (S)- and (R)-5-(hydroxymethyl)-2-pyrrolidinone as chiral
      precursors. The enantiomeric excess was determined by means of capillary
      electrophoresis, and found higher than 99.9 %. DM232 enantiomers were tested as
      cognition-enhancers in the passive-avoidance and social learning tests, and their
      ability to induce ACh release from rat cerebral cortex was also determined; in
      all the performed essays, (R)-(+)-(1) displayed higher potency than its (S)-(-)
      enantiomer, being able to elicit comparable effects at 3-fold to 10-fold lower
      doses. On the contrary, (R)-(+) and (S)-(-)-(2) showed the same amnesic potency
      when tested in the passive-avoidance test. These findings may be useful to
      clarify the mechanism of action of these substances.

PMID- 16787333
TI  - New features in synthesis of talampanel related 2,3-benzodiazepines.
AB  - Analogues of talampanel (1), a highly active AMPA antagonist 2,3-benzodiazepine,
      were synthesized, where the characteristic amino-function was either transposed
      or sterically shielded. For the key intermediates (hemiketals 6a, b) a new
      synthetic method of different mechanism was developed. The inactivity of several
      new compounds indicates the significance of the 4-amino(phenyl) function in BDZs
      of type 1.

PMID- 16787334
TI  - 3D solution structure of [Tyr3]octreotate derivatives in DMSO: structure
      differentiation of peptide core due to chelate group attachment and biologically
      active conformation.
AB  - The solution models of [Tyr3]octreotate (DPhe1-Cys2-Tyr3-DTrp4-Lys5-Thr6-Cys7
      Thr8-COOH, disulfide bridged) (I), its analogs functionalized with an open chain
      tetraamine chelator, N4-[Tyr3]octreotate (II), and the N4-(Asp)2-[Tyr3]octreotate
      (III) peptide have been determined through 2D 1H NMR spectroscopy in DMSO.
      Chemical shift analysis has been performed in an attempt to elucidate structural
      changes occurring during attachment of the tetraamine to the peptide backbone.
      NMR-derived geometrical constraints have been used in order to calculate high
      resolution conformers of the above peptides. Conformational analysis of the three
      synthetic analogues, have shown that these somatostatin analoges adopt a
      predominant antiparallel beta-sheet conformation characterized by a beta-like
      turn spanning residues DTrp4 and Lys5 which is supported in the case of N4-(Asp)2
      [Tyr3]octreotate and N4-[Tyr3]octreotate by medium range NOEs. These data
      indicate that the above-mentioned molecules adopt a rather constrained structure
      in the 4-residue loop Tyr3-Thr6. Additionally, the C-terminal of
      [Tyr3]octreotate, comprising Cys7 and Thr8, appears to form a turn-like structure
      manifested by characteristic side-chain NOEs between Lys5 and Thr8, which have
      not been detected for the other two compounds. These data are discussed in the
      light of previous structural data of Sandostatin (octreotide) and suggest that
      attachment of the N4-chelator and two Asp residues at the N-end of
      [Tyr3]octreotate impose considerable structural changes and affect the binding
      properties of these peptides. Indeed, the IC50 values determined during
      competition binding assays against the sst2 (somatostatin subtype 2 receptor)
      suggest that the presence of the N4 group enhances receptor affinity, while
      extension of peptide chain by two negatively-charged Asp residues impairs
      receptor affinity at approximately one order of magnitude.

PMID- 16787335
TI  - N-terminal anthranoyl-phenylalanine derivatives as CCK1 receptor antagonists: the
      final approach.
AB  - Starting from our lead compound, VL-0395, an anthranilic acid based CCK1 receptor
      antagonist, and following the well established "step by step" lead investigation
      strategy, we describe the final step of the anthranilic acid N-terminal
      optimization. Improvements for both affinity and selectivity towards CCK1
      receptors have been accomplished through introduction of the fluoro substituent
      at C-5 and C-7 position of the indole ring together with the appropriate
      configuration of the aminoacidic chiral center.

PMID- 16787336
TI  - Failure and success in modern drug discovery: guiding principles in the
      establishment of high probability of success drug discovery organizations.
AB  - The pharmaceutical industry currently suffers unsustainably high program failure
      rates despite our best efforts to implement drug design methods and to develop
      high throughput biochemical screening technologies over the past 20 years. While
      much of this failure is rationalized to be due to uncontrollable late stage drug
      development issues and clinical events, it has become increasingly clear that the
      choices we make in early drug discovery are vital to the ultimate failure or
      success outcomes of our drug discovery programs. The judicious selection of high
      probability of success therapeutic modalities, the rigorous determination of
      leadlikeness and druglikeness, and the all-important selection of high
      probability of success enzyme and receptor targets are the vital drivers of
      failure and success in small molecule drug discovery as it is performed in the
      age of biochemical screening. Consideration of these guiding principles will
      improve our chances of success in drug discovery, and increase our ability to
      address unmet medical need in the future.

PMID- 16787337
TI  - Adenosine phosphonoacetic acid is slowly metabolized by NDP kinase.
AB  - NDP kinase catalyzes the last step in the phosphorylation of nucleotides. It is
      also involved in the activation by cellular kinases of nucleoside analogs used in
      antiviral therapies. Adenosine phosphonoacetic acid, a close analog of ADP
      already proposed as an inhibitor of ribonucleotide reductase, was found to be a
      poor substrate for human NDP kinase, as well as a weak inhibitor with an
      equilibrium dissociation constant of 0.6 mM to be compared to 0.025 mM for ADP.
      The X-ray structure of a complex of adenosine phosphonoacetic acid and the NDP
      kinase from Dictyostelium was determined to 2.0 A resolution showing that the
      analog adopts a binding mode similar to ADP, but that no magnesium ion is present
      at the active site. As ACP may also interfere with other cellular kinases, its
      potential as a drug targeting NDP kinase or ribonucleotide reductase is likely to
      be limited due to strong side effects. The design of new molecules with a
      narrower specificity and a stronger affinity will benefit from the detailed
      knowledge of the complex ACP-NDP kinase.

PMID- 16787338
TI  - Investigation into the interaction of the phosphoporin PhoE with outer membrane
      lipids: physicochemical characterization and biological activity.
AB  - Outer membrane pore proteins such as phosphoporin (PhoE) are important
      constituents of Gram-negative bacteria such as Escherichia coli. We have studied
      the interaction of PhoE with the membrane-forming lipids phosphatidylethanolamine
      (PE) and phosphatidylglycerol (PG) from the inner and lipopolysaccharide (LPS)
      from the outer leaflet of the outer membrane. These investigations comprise
      functional aspects of the protein:lipid interaction corresponding to the outer
      membrane system as well as the activity of LPS:PhoE complexes in the infected
      host after release from the bacterial surface. The interaction of the lipids PE,
      PG, and LPS with PhoE was investigated by analysing molecular groups in the
      lipids originating from the apolar region (methylene groups), the interface
      groups (ester), and polar groups (phosphates) applying Fourier-transform infrared
      spectroscopy (FTIR), and by analysing the phase transition behaviour of the
      lipids using FTIR and differential scanning calorimetry (DSC). The activity of
      PhoE and LPS:PhoE complexes was investigated in biological test systems (human
      mononuclear cells and Limulus amebocyte lysate assay) and with phospholipid model
      membranes using fluorescence resonance energy transfer spectroscopy (FRET). The
      results show a strong influence of PhoE on the mobility of the lipids leading to
      a considerable fluidization of the acyl chains of LPS, but much less to those
      from phospholipids: PhoE released from the outer membrane still contains slight
      contaminations of LPS, but its strong cytokine-inducing ability in mononuclear
      cells, which is not found in the LPS-specific Limulus amebocyte lysate test,
      indicates an LPS-independent mechanism of cell activation.

PMID- 16787339
TI  - Competitive reactions of L-methionine and 5'-GMP towards platinum (II) complexes.
AB  - The complex-formation reactions of the platinum(II) complexes, [Pt(dien)H2O]2+,
      [PtCl(dien)]+ and [PtBr(dien)]+ (dien is diethylenetriamine) with some
      biologically relevant ligands such as inosine (INO), inosine-5'-monophosphate (5'
      IMP), guanosine-5'-monophosphate (5'-GMP), glutathione (GSH) and L-methionine (S
      meth), were studied by UV-Vis (UV-Visible) spectrophotometry and 1H NMR
      spectroscopy. Reactions of the [PtCl(dien)]+ with L-methionine were studied in
      the presence and absence of 5'-GMP. The rate constants clearly showed a kinetic
      preference toward L-methionine. However, competitive reactions of [PtCl(dien)]+
      with L-methionine and 5'-GMP demonstrated initially rapid formation of
      [Pt(dien)(S-meth)]2+ followed by displacement of L-methionine by 5'-GMP. In the
      later stages the concentration of [Pt(dien)(N7-GMP )]2+ is predominant. The
      results are analyzed in reference to the anti-tumour activity of Pt(II)
      complexes.

PMID- 16787340
TI  - The role of copper in development of drug resistance in murine carcinoma.
AB  - Multidrug resistance (MDR) is a major obstacle to successful application of
      cancer chemotherapy and also a basic problem in cancer biology. Studies on the
      molecular basis of MDR have revealed that a number of proteins over express in
      multidrug resistant cells viz., multidrug resistant MDR1 gene product P
      glycoprotein, the multidrug resistance-associated protein (MRP) and enzymes
      associated with the glutathione (GSH) metabolism. Decreased expression or altered
      activity of topoisomerase II has also been implicated in MDR. In the present
      investigation a number of changes in phase II detoxification parameters have been
      noticed in drug resistant cells but the novel aspect of the present report is the
      observation that the metal copper is involved in drug resistance. Although copper
      plays important roles in many human and other biological systems and even in the
      treatment of cancer but the relation of Cu and drug resistance has not so far
      been studied in detailed. The present report describes the novel findings that
      the level of copper increases with the development of drug resistance in Ehrlich
      ascites carcinoma and in Lewis lung carcinoma cells and also in serum of mice
      bearing drug resistant cancer cells compared to mice bearing drug sensitive
      cells; the work indicates the important aspect of treating drug resistant cancer
      patients by lowering Cu level in the cancerous cells and serum prior to
      treatment.

PMID- 16787341
TI  - Isolation of bioactive natural products from myxomycetes.
AB  - The Myxomycetes (true slime molds) are an unusual group of primitive organisms
      that may be assigned to one of the lowest classes of eukaryotes. As their fruit
      bodies are very small and it is very difficult to collect much quantity of slime
      molds, few studies have been made on the chemistry of myxomycetes. Cultivation of
      the plasmodium of myxomycetes in a practical scale for natural products chemistry
      studies is known only for very limited species. Here is described a review on the
      recent results on isolation of bioactive natural products from myxomycetes
      obtained in these two years in the laboratories. Spore germination experiments
      were studied of hundreds of field-collected myxomycetes collected in Japan and
      succeeded in laboratory culture of plasmodia of several myxomycetes in a
      practical scale for natural products chemistry studies. As a result,
      pyrroloiminoquinones, polyene yellow pigments, and a peptide lactone from
      cultured plasmodia of Didymium iridis, Physarum rigidum and P. melleum,
      respectively were isolated. New naphthoquinone pigments,
      cycloanthranilylprolines, tyrosine-kinase inhibitory bisindoles, and a cytotoxic
      triterpenoid aldehyde lactone were also isolated from field-collected fruit
      bodies of Cribraria purpurea, Fuligo candida, Tubifera casparyi, and Tubifera
      dimorphotheca, respectively.

PMID- 16787342
TI  - Quinaldine derivatives: preparation and biological activity.
AB  - The series of quinaldine derivatives were prepared, some of them by means of
      novel synthetic methods. The synthetic approach, analytical and spectroscopic
      data of all newly synthesized compounds are presented. The prepared compounds
      were tested for their in vitro antifungal activity as well as for their
      photosynthesis-inhibiting activity (the inhibition of photosynthetic electron
      transport in spinach chloroplasts (Spinacia oleracea L.) and the reduction of
      chlorophyll content in Chlorella vulgaris Beij.). Structure-activity
      relationships among the chemical structure, the physical properties and the
      biological activities of the evaluated compounds are discussed in the article.

PMID- 16787343
TI  - 8-(Heteroaryl)phenalkyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones as opioid
      receptor modulators.
AB  - A series of N-biarylalkyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones were
      prepared and evaluated for biological activity at opioid (mu, delta, kappa) and
      opioid receptor like-1 (ORL-1) G-protein coupled receptors. Substitution on the
      biaryl moiety produced enhanced affinity for the mu-opioid receptor.

PMID- 16787345
TI  - Antitumour antibiotics with potent activity against multidrug resistant (MDR)
      Staphylococcus aureus: a new approach to targeting resistant bacteria.
AB  - As hospital reports of strains of resistant bacteria are continuing to increase,
      a new approach is required for the identification of small molecules with
      antibacterial activity. Natural products that bind covalently to their biological
      target have been largely unexplored, although in the field of cancer
      chemotherapy, such molecules have been shown to counter resistance developed
      through efflux mechanisms. The azinomycins are potent antitumour agents that
      alkylate DNA and one of the natural products, compound 1, is a mono-alkylator
      that has been reported to retain potent antitumour activity. All four
      diastereomers of 1 were synthesized via a route involving late stage introduction
      of the epoxide stereocentre and separation of the resulting compounds. A non
      alkylating analogue and a potential alkylator that cannot intercalate were also
      made. All four diastereomers are potent antibacterial agents in cell lines
      containing efflux-based resistance mechanisms. MIC values in the range of 0.25
      1.0 microg/ml were observed. Comparison with the antitumour activity of the
      compounds suggests that the antibacterial activity stems from a similar mechanism
      of action involving DNA alkylation. As the ultimate molecular target of the
      azinomycins is unknown, bacterial strains may represent an interesting route for
      the discovery of the downstream mechanisms affected by DNA alkylation.

PMID- 16787344
TI  - Comparison of radiohaloanalogues of meta-iodobenzylguanidine (MIBG) for a
      combined gene- and targeted radiotherapy approach to bladder carcinoma.
AB  - Targeted radiotherapy using radiolabelled meta-iodobenzylguanidine (MIBG) is a
      promising treatment option for bladder cancer, restricting the effects of
      radiotherapy to malignant cells thereby increasing efficacy and decreasing
      morbidity of radiotherapy. We investigated the efficacy of a combined gene
      therapy and targeted radiotherapy approach for bladder cancer using radiolabelled
      MIBG. The effectiveness of alternative radiohalogens and alternative preparations
      of radiolabelled MIBG for this therapeutic strategy were compared. Bladder cancer
      cells, EJ138, were transfected with a gene encoding the noradrenaline transporter
      (NAT) under the control of a tumour specific telomerase promoter, enabling them
      to actively take up radiolabelled MIBG. This resulted in tumour-specific cell
      kill. Uptake and retention of radioactivity in cells transfected with the NAT
      gene were compared with that obtained in cells transfected with the sodium iodide
      symporter (NIS) gene. Substantially greater uptake and longer retention of
      radioactivity in NAT-transfected cells was observed. Carrier-added (c.a.)
      [131I]MIBG, no-carrier added (n.c.a.) [131I]MIBG, and [211At]-labelled
      benzylguanidine (i.e. [211At] meta-astatobenzylguanidine (MABG)) were compared
      with respect to efficiency of induction of cell kill. N.c.a[(131)I]MIBG was more
      cytotoxic than c.a.[131I]MIBG. However, the alpha-emitter [211At]MABG was, by
      three orders of magnitude, more effective in causing tumour cell kill than the
      beta-emitter [131I]MIBG. We conclude that NAT gene transfer combined with the
      administration of n.c.a.[131I]MIBG or [211At]MABG, is a promising novel treatment
      approach for bladder cancer therapy.

PMID- 16787346
TI  - Resveratrol enhances UVA-induced DNA damage in HaCaT human keratinocytes.
AB  - Resveratrol, a polyphenolic phytoalexin, is a very effective antioxidant that
      also exhibits strong antiproliferative and anti-inflammatory properties. Recent
      studies have provided support for the use of resveratrol in human cancer
      chemoprevention, in combination with either chemotherapeutic drugs or cytotoxic
      factors for a most efficient treatment of drug refractory tumor cells.
      Resveratrol is also widely used in topical preparations, as a chemoprotective
      compound against development of several cutaneous disorders, including skin
      cancer. Nevertheless, the combined effect of resveratrol and UVA irradiation on
      cellular toxicity and DNA damage has never been assessed. The aim of this work
      was to investigate the effect of resveratrol on cell fate in immortalized human
      keratinocytes HaCaT cells. The results indicated that resveratrol potentiates the
      production of significant amounts of 8-oxo-7,8-dihydro-2'-deoxyguanosine in UVA
      irradiated genomic DNA. Moreover, the combination of resveratrol with UVA
      significantly enhances the induction of DNA strand breaks and cell death in HaCaT
      keratinocytes. The conclusion is a potential hazardous effect of topical
      application of resveratrol, particularly on regions exposed to sunlight.

PMID- 16787347
TI  - The rationale and development of new drugs to treat HIV infection.
AB  - Fewer than one million HIV infected individuals are currently receiving
      antiretroviral therapy. Present antiretroviral therapy costs between 10,000
      dollars and 20,000 dollars per year, which provides excellent value for money in
      developed countries with a cost of about 10,000 dollars per life year saved; this
      compares very favourably with other therapies in chronic use. Recent studies have
      demonstrated a dramatic decline in HIV and AIDS related morbidity and mortality
      across developed countries and these reductions have been sustained since the
      introduction of highly active antiretroviral therapy (HAART) since 1996. The use
      of HAART has been associated with specific toxicities related to the drug class,
      problems with adherence with the subsequent emergence of viral isolates and
      resistance associated mutations. The replacement of older therapies with newer
      drugs that avoid cross resistance even within the same class of antiretroviral,
      represents a new hope in retroviral targeting.

PMID- 16787348
TI  - Site- and cell-type- specific induction of intestinal inducible nitric oxide
      synthase in a rat model of endotoxemia.
AB  - The intestine is one of the major organs that are involved in sepsis. The
      inducible isoform of nitric oxide synthase (iNOS) is known to play a critical
      role in the pathogenesis of septic tissue injury by generating excess amount of
      nitric oxide (NO) in response to cytokines and endotoxin. In this study, we
      examined changes in gene expression of iNOS in various regions of the intestine
      as well as the distribution of iNOS protein in the intestinal cells in a rat
      model of endotoxemia produced by intraperitoneal injection of lipopolysaccharide
      (LPS; 10 mg/kg). While iNOS mRNA was undetectable in the intestine of untreated
      control animals, it underwent marked induction following LPS treatment. Induction
      of iNOS mRNA in the ileum was marked and biphasic, while it was also marked but
      monophasic in the jejunum. The induction of iNOS mRNA was maximal in the ileum.
      The administration of interleukin-6 (IL-6) upregulated intestinal iNOS gene
      expression specifically in the ileum. Consistent with enhanced iNOS gene
      expression, iNOS protein was markedly expressed in the ileum after LPS treatment,
      exclusively in the mucosal epithelium both at crypt and villus cells, although
      more prominently in the former. These findings suggested that intestinal iNOS
      expression was upregulated both at transcriptional and protein levels not only in
      a site-specific, but also in a cell type-specific manner in a rat model of
      endotoxemia, possibly through increasing serum IL-6 levels. Differential
      regulation of iNOS expression along the longitudinal and crypt-villus axes of the
      gut might be a determinant of the pattern of sepsis-induced intestinal damage.

PMID- 16787349
TI  - Identification and evaluation of molecular properties related to preclinical
      optimization and clinical fate.
AB  - The economic case for fundamental changes that are required to ensure long term
      viability of the pharmaceutical industry demands a close look at which compounds
      are advanced into clinical development. This perspective will cover recent
      efforts that have had the greatest influence on defining the optimal range of
      physical properties of compounds that are intended to act as human therapeutic
      agents. Our focus will be on models and properties that are most amenable to
      change via synthetic design, are potentially fixable in the lead optimization
      process, and have the greatest impact on overall attrition in clinical
      development. In particular, we will examine the optimal physicochemical
      properties for oral absorption based on solubility, permeability, and a few
      easily computed parameters. Additionally, the fate of compounds that have entered
      clinical trials provides a compelling case for adhering to the defined properties
      ranges. Finally, emerging data suggests that there has been a shift in the
      leading causes of compound attrition, and attention should now be focused on
      building toxicological models to guide drug discovery efforts.

PMID- 16787350
TI  - The modulation of inter-organelle cross-talk to control apoptosis.
AB  - Mitochondria fulfill a wide array of functions dedicated to the energetic
      metabolism as well as the control of cell death. These functions imply that
      mitochondria can be activated by a variety of signals and can integrate them to
      trigger a process called mitochondrial membrane permeabilization (MMP), which
      induces the ultimate events of apoptosis. MMP consists in a sudden increase in
      the permeability of mitochondrial membrane that results in the release of
      critical proapoptotic intermembrane space effectors into the cytosol such as
      cytochrome c, apoptosis-inducing factor (AIF), Smac/Diablo, Endo G, and pro
      caspases. In many models of apoptosis, mitochondrial translocation of proteins
      and/or lipids concomitantly with alterations of the intracellular milieu has been
      shown to activate MMP. This applies to tumor suppressors of the Bax/Bcl-2 family
      (Bax, Bad, Bid, Bim), several protein kinases (Akt, ASK1, hexokinase), p53, NF
      kappaB, and nuclear orphan receptors such as TR3/Nur77. After mitochondrial
      membrane association, these proteins target constitutive mitochondrial proteins
      including the permeability transition pore complex (PTPC), Bcl-X(L), HSP70,
      and/or the lipid interphase. Subsequently, they switch their vital function into
      a lethal function to promote membrane permeabilization and protein release. In
      this review, we will describe some general rules of inter-organelle cross-talk
      activating MMP and will review selected examples of pro-apoptotic protein
      translocation. Finally, we will propose new pharmacological strategies to
      modulate this process in a therapeutic perspective.

PMID- 16787351
TI  - Development of gene therapies for cardiovascular and renal diseases by nucleic
      acid medicines.
AB  - Nucleic acid medicines such as antisense DNA, antisense peptide nucleic acid
      (PNA), ribozyme, and decoy are expected to be novel therapeutic strategy for
      sever diseases which are resistant to present therapy. We have developed
      antisense DNA, antisense PNA and ribozyme targeting platelet-derived growth
      factor (PDGF) A-chain and transforming growth factor-beta1 (TGF-beta1) for
      arterial proliferative diseases such as coronary artery stenosis after
      angioplasty or stent implantation, hypertensive vascular diseases and
      atherosclerosis, and progressive renal diseases. Antisense DNA to PDGF A-chain
      inhibited arterial growth in spontaneously hypertensive rats without lowering
      blood pressure and inhibited the neointima formation of pig coronary artery after
      stent implantation. Ribozymes to PDGF A-chain and TGF-beta1 specifically
      inhibited the target transcripts and prevented the neointima formation. Ribozymes
      to TGF-beta1 improved renal damages in hypertensive rats. These nucleic acid
      medicines targeting PDGF A-chain and TGF-beta1 will be feasible gene therapies
      for the arterial proliferative diseases and progressive renal diseases. Pyrrole
      imidazole polyamides are novel gene silencing compound, which bind to minor grove
      of double strand DNA by base-specific manner to inhibit gene expression. We
      developed pyrrole-imidazole polyamide to TGF-beta1 and confirmed that the
      polyamide binds to the TGF-beta1 promoter. The polyamide inhibited TGF-beta1
      promoter activity and decreased expression of TGF-beta1 in vitro and in vivo. The
      polyamide markedly improved the renal injury in hypertensive rats. The pyrrole
      imidazole polyamide will be a novel gene silencing agent for cardiovascular and
      renal diseases.

PMID- 16787352
TI  - Simultaneous hydrogenolysis of p-nitrobenzyl esters and carbamates side-chains in
      the THF 1beta-carbapenem OCA-983 in biphasic media.
AB  - Deprotection of p-nitrobenzyl esters and valyl carbamates in carbapenem CL
      192,276 produced the active compound OCA-983 in excellent yields. Straight chain
      alkanols such as 1-butanol, 1-pentanol and 1-hexanol in water at certain ratios
      were effective solvent systems. Alkyl acetates in water also resulted in
      simultaneous deprotection of PNB and PNZ side-chains albeit at slower rates. The
      deprotected carbapenem was isolated in excellent yield and purity after removal
      of the aqueous media. This procedure is applicable to sensitive compounds that
      are soluble in water without the need to use a buffer and allows for ease of
      isolation from the aqueous phase.

PMID- 16787353
TI  - New cathepsin d inhibitors with hydroxyethylamine isosteres: preparation and
      characterization.
AB  - The lysosomal aspartyl protease, cathepsin D, has been suggested to play a role
      in the metastatic potential of several types of cancer. Cathepsin D is secreted
      by malignant cells, and is believed to be involved in the breakdown of the
      extracellular matrix. High levels of active cathepsin D have been found in colon
      cancer, prostate cancer, uterine cancer and ovarian cancer. Also cathepsin D has
      recently been associated with the development of Alzheimer's disease.
      Hydroxyethyl isosteres with cyclic tertiary amine have proven to be clinically
      useful as inhibitors of aspartyl proteases similar to cathepsin D in activity,
      such as the HIV-1 aspartyl protease. In the present study twenty-eight compounds
      containing (hydroxyethyl)amine isosteres with cyclic tertiary amines have been
      synthesized. These compounds show significant activity as cathepsin D inhibitors,
      many with IC(50) values in the nanomolar range. For example, the compounds that
      contain hydroxyethylamines where the amine is formed from N-piperazine-2
      carboxylic acid methyl ester, 4y-bb, show IC(50) values ranging from 2.5 to 15
      nM.

PMID- 16787354
TI  - Thienocinnolinone alkanoic acid derivatives as aldose reductase inhibitors.
AB  - A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic
      acids was prepared and tested for aldose reductase (ALR2) inhibitory activities.
      These compounds showed significant inhibitory activity against bovine lens ALR2,
      with the best compound 2e showing an IC(50) value of 31.4 microM. The presence of
      the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold
      caused a decrease of the inhibitory potency by a factor of about 4 with respect
      to the unsubstituted parent compound, while the presence of a C8-methyl group,
      considered in a previous paper decreased the activity by a factor of about 2.
      Moreover, the length of the N2 alkanoic chain influences strongly the enzyme
      inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are
      acetic acid derivatives, in the case of thienocinnolinone compounds, homologues
      higher than acetic acids showed to be more active.

PMID- 16787355
TI  - Poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide enhances apoptosis
      induction by platinum complexes in cisplatin-resistant tumor cells.
AB  - Cisplatin is one of the most widely used antitumor drugs. However, as all the
      anticancer drugs currently used in clinic, cisplatin shows the phenomenon of drug
      resistance (intrinsic or acquired) against a wide variety of tumors. Poly (ADP
      ribose) polymerase-1 is an enzyme involved in DNA repair and apoptotic cell
      death, which may be inhibited to increase cisplatin chemosensitivity of tumor
      cells so that cisplatin resistance may be circumvented. In the present study we
      report that PARP-1 inhibitor 3-aminobenzamide (3-AB) increases the cytotoxic
      activity of the platinum compounds cisplatin, trans-[PtCl(2)(4
      picoline)(piperazine)] and transplatin against CH1cisR cisplatin-resistant
      ovarian tumor cells. In fact, a concentration of 3-AB of 1 mM not only increases
      the cytotoxic activity of these platinum complexes but also switches the mode of
      cell death from necrosis to apoptosis. Altogether, these data suggest that
      pharmacological modulation of PARP-1 by inhibitors may be a suitable strategy to
      fight against tumor resistance to platinum drugs.

PMID- 16787356
TI  - Synthesis and structure-activity relationship on anticonvulsant aryl
      semicarbazones.
AB  - Seven series of various substituted aryl semicarbazones were synthesized and
      evaluated for anticonvulsant activity in the maximal electroshock seizure (MES)
      and subcutaneous pentylenetetrazole (scPTZ) induced seizure threshold tests. A
      comprehensive structure-activity relationship was derived comparing the
      substituents on the aryl ring and in the carbimino terminal. Generally the order
      of activity was 4-F > 2-Br = 3-Br = 4-Cl > 4-CH(3) > 4-Br > 3-Cl > 3-CH(3) with
      respect to the primary aryl group. Most of the compounds exhibited activity both
      in the MES and scPTZ screens. The 4-fluorophenyl substituted semicarbazones (5a
      5y) emerged as the most potent compounds exhibiting anticonvulsant activity in
      mouse intraperitoneal (i.p.) and rat per oral (p.o.) MES, scPTZ and psychomotor
      seizure (6 Hz) screens.

PMID- 16787357
TI  - Sensitization of multidrug resistant (MDR) cancer cells to vinblastine by novel
      acridones: correlation between anti-calmodulin activity and anti-MDR activity.
AB  - Multidrug resistance (MDR) of cancer cells remains to be an important cause of
      chemotherapy failure. Search for the new MDR reversal agents is still an
      unceasing challenge for the scientists. In an attempt to find clinically useful
      modulators of MDR, a series of 19 N(10)-substituted-2-bromoacridones has been
      synthesized. Parent compound 1, prepared by the Ullmann condensation of o
      chlorobenzoic acid and p-bromoaniline, undergoes N-alkylation in the presence of
      a phase transfer catalyst. N-(omega-Chloroalkyl) analogues were subjected to
      iodide catalyzed nucleophilic substitution reaction with various secondary amines
      to get the products 3-10 and 12-19, which increased the uptake of vinblastine
      (VLB) in MDR KBCh(R)-8-5 cells to a greater extent (1.25 to 1.9-fold) than did a
      similar concentration of the standard modulator, verapamil (VRP). Results of the
      efflux experiment showed that each modulator significantly inhibited the efflux
      of VLB, suggesting that they may be competitors for P-gp. All the compounds
      effectively compete with [(3)H] azidopine for binding to P-gp, pointed out this
      transport membrane protein as their likely site of action. Compounds at IC(10)
      were evaluated for their efficacy to modulate the cytotoxicity of VLB in KBCh(R)
      8-5 cells and found that the modulators enhanced the cytotoxicity of VLB by 3.8
      to 34-fold. The study on the structure-activity relationship revealed that
      substitution of hydrogen atom at position C-2 in acridone nucleus by a bromine
      atom increased the cytotoxic and anti-MDR activities. The ability of acridones to
      inhibit calmodulin-dependent cyclic AMP phosphodiesterase has been determined and
      the results have shown a strong positive correlation between anti-calmodulin
      activity and cytotoxicity in KBCh(R)-8-5 cells or anti-MDR activity.

PMID- 16787358
TI  - Anti-proliferative effects of novel glyco-lipid-arsenicals (III) on MCF-7 human
      breast cancer cells.
AB  - Arsenic trioxide appears to be effective in the treatment of pro-myelocytic
      leukaemia. The substituted phenylarsen(III)oxides are highly polar, they have a
      high tendency to undergo oxidation to As (V) and to form oligomers, to prevent
      this we protected the As-(OH)(2) group as cyclic dithiaarsanes. To increase the
      compound's biological stability and passive diffusion we conjugated the compound
      of interest with lipoamino acids (Laas). Alternatively, we further conjugated the
      dithiaarsane derivative with a carbohydrate to utilize active transport systems
      and to target compound. We investigated two novel glyco-lipid arsenicals (III)
      (compounds 9 and 11) for their ability to initiate MCF-7 breast cancer cell death
      and characterized the mechanism by which death was initiated. A significant
      decrease in MCF-7 cell proliferation was observed using 1 microM and 10 microM
      compound (11) and 10 microM of compound (9). Treatment with compound (11)
      triggered apoptosis of MFC-7 cells while compound (9) induced inhibition of
      cellular proliferation was not via rapid induction of apoptosis and more likely
      reflected necrosis and/or alterations in the cell cycle. Differences in the anti
      proliferative potency of the two compounds indicate that structural modifications
      influence effectiveness.

PMID- 16787359
TI  - Current status of virtual screening as analysed by target class.
AB  - In silico virtual screening for drug discovery has become a hot topic in
      medicinal chemistry research during the last 5 years, growing from a largely
      academic pursuit concerned principally with validating the methods used, to a
      major early-stage technique for lead discovery in the pharmaceutical industry. In
      this review we highlight a few recent successes in ligand docking associated with
      virtual screening, paying particular attention to four major target classes of
      pharmaceutical interest (G Protein-Coupled receptors, nuclear hormone receptors,
      kinases, proteases). We also discuss some emerging trends in the field, some
      common limitations, and how they are being overcome.

PMID- 16787360
TI  - Synthesis of variously substituted 3-phenoxymethyl quinoxalin-2-ones and
      quinoxalines capable to potentiate in vitro the antiproliferative activity of
      anticancer drugs in multi-drug resistant cell lines.
AB  - Two series of 1,6-dimethyl-3-phenoxymethylquinoxalin-2-ones and 1-benzyl-3
      phenoxymethyl-7-trifluoromethylquinoxalin-2-ones, and a series of 2-benzyloxy-3
      phenoxymethyl-7-trifluoromethylquinoxaline were synthesized. Their capability to
      restore/potentiate the antiproliferative activity of clinically useful drugs,
      such as doxorubicin (Doxo), vincristine (VCR) and etoposide (VP16), in drug
      resistant human nasopharyngeal carcinoma KB cells (KB(WT), KB(MDR), KB(7D)and
      KB(V20C)) was evaluated. In vitro data show that many quinoxalin-2-ones and
      quinoxalines potentiate the antiproliferative activity of Doxo and VCR in tumor
      derived MDR cell lines. In this series, 17a turned out to be the most potent
      quinoxaline derivative in potentiating the antiproliferative activity of
      doxorubicin and vincristine against KB(MDR) and KB(V20C) resistant cell lines,
      respectively.

PMID- 16787361
TI  - New cysteine derivatives with antiproliferative activity on melanoma cells.
AB  - Here we describe the rational design, computer-aided virtual ligand docking and
      synthesis of 19 nonpeptidic compounds designed to inhibit histone deacetylases
      and kill melanoma cells. Compounds were derived from cysteine, fused at the S
      terminus to 4-butanoyl hydroxamate, and at the N-terminus to 4
      (dimethylamino)benzoic acid. The latter was extended by coupling to amines to
      form a small library of prospective anti-cancer compounds. Four compounds were
      cytotoxic at sub-micromolar concentrations against cells of a particularly
      aggressive human melanoma (MM96L), and nine compounds showed selectivities of
      >or=5:1 for killing human melanoma instead of normal human fibroblast cells. The
      most active compounds were shown to cause hyperacetylation of histones due to
      inhibition of histone deacetylases. Further refinement of these compounds may
      produce an anti-tumor drug suitable for treating melanoma.

PMID- 16787362
TI  - Design, synthesis and antimalarial activity of a new class of iron chelators.
AB  - Iron is crucial for many biochemical reactions involved in the growth and
      multiplication of the malaria parasite Plasmodium falciparum. There are many
      reports indicating that the iron chelators have antimalarial activity in vitro,
      in vivo and in human studies. However, these compounds suffer from a number of
      serious problems such as limited membrane permeability, short half-life and
      require long subcutaneous infusions. To circumvent these drawbacks we have
      designed a new class of iron chelators, wherein EDTA is tethered to 4
      aminoquinoline. Here 4-aminoquinoline scaffold is used as a carrier to penetrate
      biological membrane and facilitate targetting the compounds to acidic food
      vacuole of the parasite. This study describes the synthesis of novel iron
      chelators and their in vitro antimalarial activity against P. falciparum strain
      of NF-54. The calculated LogP values of these compounds suggest the importance of
      lipophilicity for the antimalarial activity. The EDTA esters are more active than
      the corresponding acids. The biophysical studies suggest that these compounds may
      inhibit the parasite growth by iron chelation mechanism.

PMID- 16787363
TI  - Novel (S)-(-)- and R-(+)-seco-iso-cyclopropylfurano[e]indoline-5,6,7
      trimethoxyindole-2-carboxamide (iso-CFI) analogs of duocarmycin C2: synthesis and
      biological evaluation.
AB  - Racemic seco-iso-CFI (cyclopropylfurano[e]indoline) analogs of the duocarmycins
      and CC-1065 have recently been reported by our group. These compounds covalently
      react with AT-rich sequences of DNA, and they exhibit potent cytotoxicity against
      cancer cells but are less toxic to normal bone marrow cells. This article details
      the synthesis of enantiomerically pure (S)-(-)- and R-(+)-seco-iso-CFI
      (cyclopropylfurano[e]indoline)-5,6,7-trimethoxyindole-2-carboxamide analogs, (S)
      (-)-1 and (R)-(+)-1, respectively. The covalent DNA binding properties and
      cytotoxicity of both enantiomers against L1210 murine leukemia and B16 murine
      melanoma cells grown in culture are reported and compared to racemate (+/-)-1.
      The natural (S)-(-)-enantiomer of 1 is more reactive with DNA and more cytotoxic
      than its unnatural mirror image and the racemic mixture.

PMID- 16787364
TI  - Antiestrogenically active 2-benzyl-1,1-diarylbut-2-enes: synthesis, structure
      activity relationships and molecular modeling study for flexible estrogen
      receptor antagonists.
AB  - The nonsteroidal antiestrogen drug tamoxifen is the endocrine treatment of choice
      for estrogen receptor positive breast cancer, while the related estrogen receptor
      antagonist raloxifene is an effective therapeutic intervention for osteoporosis.
      We report the development of a series of hydroxylated 2-benzyl-1,1-diarylbut-2
      enes containing a flexible core scaffold structure differing from the 1,1,2
      triarylethylene typical of tamoxifen analogues. In this novel structure, a
      benzylic methylene group acts as a flexible hinge linking the aryl ring C and the
      ethylene group. The target products were synthesized using a McMurry coupling
      (titanium tetrachloride/zinc mediated) procedure. In this study, introduction of
      hydroxyl, ether and ester substitution on ring C was explored in an attempt to
      correlate possible metabolic activation in Ring C with antiproliferative
      activity. These Ring C substituted products showed potent antiproliferative
      activity against the MCF-7 human breast cancer cell line. The compounds were also
      shown to have high binding affinity for the estrogen receptor (IC(50) values in
      the low nanomolar range) together with up to 17 fold selectivity for
      ERalpha/beta. Some compounds demonstrated antiestrogenic activity in the Ishikawa
      cells at 40 nM without estrogenic stimulation. The products also displayed a pro
      apoptotic effect in MCF-7 cells in a flow cytometry based assay. In a
      computational study, docked structures of the active compounds were compared with
      the X-ray crystal structures for the complexes of ERalpha with 4-hydroxytamoxifen
      and ERbeta with raloxifene. The novel ligands are predicted to bind to the
      ERalpha and ERbeta in an antiestrogenic orientation, with expected differences
      obtained in the alignment of the benzylic ring C within the ligand binding
      domain.

PMID- 16787365
TI  - Curcumin is an inhibitor of p300 histone acetylatransferase.
AB  - Histone acetyltransferases (HATs), and p300/CBP in particular, have been
      implicated in cancer cell growth and survival, and as such, HATs represent novel,
      therapeutically relevant molecular targets for drug development. In this study,
      we demonstrate that the small molecule natural product curcumin, whose medicinal
      properties have long been recognized in India and Southeast Asia, is a selective
      HAT inhibitor. Furthermore the data indicate that alpha, beta unsaturated
      carbonyl groups in the curcumin side chain function as Michael reaction sites and
      that the Michael reaction acceptor functionality of curcumin is required for its
      HAT-inhibitory activity. In cells, curcumin promoted proteasome-dependent
      degradation of p300 and the closely related CBP protein without affecting the
      HATs PCAF or GCN5. In addition to inducing p300 degradation curcumin inhibited
      the acetyltransferase activity of purified p300 as assessed using either histone
      H3 or p53 as substrate. Radiolabeled curcumin formed a covalent association with
      p300, and tetrahydrocurcumin displayed no p300 inhibitory activity, consistent
      with a Michael reaction-dependent mechanism. Finally, curcumin was able to
      effectively block histone hyperacetylation in both PC3-M prostate cancer cells
      and peripheral blood lymphocytes induced by the histone deacetylase inhibitor MS
      275. These data thus identify the medicinal natural product curcumin as a novel
      lead compound for development of possibly therapeutic, p300/CBP-specific HAT
      inhibitors.

PMID- 16787366
TI  - Drug evolution concept in drug design: 2. Chimera method.
AB  - The drug evolution method represents a novel approach towards efficient rational
      drug design by implementing the drug evolution concept to the creation and
      development of general chemical libraries with the purpose of allowing the
      identification of drug candidates with improved odds and lesser costs than the
      traditional drug design strategies. As another example of successful translation
      of the biological evolution into chemical evolution, the chimera method comprises
      the grafting of selected building blocks, identified through a basic search
      within a drug library, onto the same substitution sites on a rationally chosen
      scaffold. The method allows the creation of a library containing both drugs and
      prospective drug candidates without any priorly required knowledge on the pursued
      disease or molecular target. Two libraries having scaffolds derived from para
      aminobenzoic acid and salicylic acid have exemplified the application of the
      chimera method. The validation of the method has been achieved through the high
      number of recognized drugs within the library, which exhibit in the same time a
      wide variety of therapeutic activities and interact with a broad spectrum of
      molecular targets. The drug-enriched chimera libraries are expected to provide a
      highly efficient access to novel drug candidates whose unspecified therapeutic
      effects should be further revealed through high-throughput screening.

PMID- 16787367
TI  - FAMS complex: a fully automated homology modeling system for protein complex
      structures.
AB  - The formation of a protein-protein complex is responsible for many biological
      functions; therefore, three-dimensional structures of protein complexes are
      essential for deeper understandings of protein functions and the mechanisms of
      diseases at the atomic level. However, compared with individual proteins, complex
      structures are difficult to solve experimentally because of technical
      limitations. Thus a method that can predict protein complex structures would be
      invaluable. In this study, we developed new software, FAMS Complex; a fully
      automated homology modeling system for protein complex structures consisting of
      two or more molecules. FAMS Complex requires only sequences and alignments of the
      target protein as input and constructs all molecules simultaneously and
      automatically. FAMS Complex is likely to become an essential tool for structure
      based drug design, such as in silico screening to accelerate drug discovery
      before an experimental structure is solved. Moreover, in this post-genomic era
      when huge amounts of protein sequence information are available, a major goal is
      the determination of protein-protein interaction networks on a genomic scale.
      FAMS Complex will contribute to this goal, because its procedure is fully
      automated and so is suited for large-scale genome wide modeling.

PMID- 16787368
TI  - Investigation of the route of absorption of lipid and sugar modified leu
      enkephalin analogues and their enzymatic stability using the caco-2 cell
      monolayer system.
AB  - It has been demonstrated that conjugation of lipoamino acids or glucose units to
      the endogenous opioid peptide, Leu-enkephalin can significantly improve the
      peptide's metabolic stability and absorption across biological barriers. The
      purpose of this study was to investigate the possible involvement of specific
      carrier proteins in the absorption of these peptide conjugates. A series of lipo-
      glycol- and liposaccharide peptide conjugates were synthesised and examined using
      the Caco-2 monolayer assay for evidence of interaction with the human H(+)
      coupled oligopeptide transporter (hPepT1), glucose transporters and the multidrug
      resistance efflux pump, p-glycoprotein. The investigation involved determining
      the apparent permeability of each compound in the absence of any inhibitors and
      comparing this to the apparent permeabilities of each compound in the presence of
      glycylsarcosine, glucose or vinblastine, respective inhibitors of the above
      mentioned transporters. None of the peptide conjugates were found to be
      substrates for p-glycoprotein. Of the six peptide conjugates examined, only the C
      terminus glucose conjugate of Leu-enkephalin (Enk-glu) showed evidence of
      transport by both glucose transporters and hPepT1. In contrast, N-terminus
      conjugation of both lipids and sugars appeared to provide the greatest protection
      against enzymatic degradation.

PMID- 16787369
TI  - Mitogen activated protein (MAP) kinases: development of ATP and non-ATP dependent
      inhibitors.
AB  - Extracellular signals regulate most of the body's physiological functions through
      the MAP kinase signaling pathways. These MAP kinase signaling pathways are
      normally under tight regulation such that activation and inactivation occurs only
      when needed. However, aberrant regulation observed with naturally occurring
      mutations in specific signaling proteins often results in constitutive activation
      of the MAP kinases and is involved in several pathophysiological conditions, such
      as cancer, neurodegeneration, and inflammation. As such, much effort has been
      expended to develop inhibitory molecules of the MAP kinase signaling pathways.
      Several compounds have been identified that inhibit MAP kinase signaling by
      targeting receptors or other proteins upstream of the MAP kinases. The
      development of specific inhibitors of the MAP kinases themselves has been less
      successful and only a few compounds, which interfere with ATP binding, have been
      identified. A common problem with kinase inhibitors that compete with ATP binding
      is their lack of specificity. Thus, alternative approaches to inhibit MAP kinase
      function are being sought. The MAP kinase proteins contain docking domains that
      direct the interactions with a variety of substrate proteins. Using the 3
      dimensional structure of MAP kinases and computer modeling, molecules that target
      specific docking domains and selectively disrupt substrate interactions are being
      developed. This non-ATP interfering approach may allow the selective inhibition
      of MAP kinase substrates involved in disease processes while preserving MAP
      kinase functions associated with normal cells.

PMID- 16787372
TI  - Solid-phase synthesis of quinazoline-2,4-diones and their analogues from resin
      bound compounds with primary amines.
AB  - Solid-phase organic synthesis of heterocyclic compounds on solid-support has been
      a focus of recent investigations because of the potential applicability of these
      compounds toward a variety of drug targets. Among the various heterocycles, we
      have been especially interested in quinazoline-2,4-diones because of the wide
      range of their bioactivities. Therefore, in this article we review methods for
      the solid-phase synthesis of quinazoline-2,4-diones and their analogues. Since
      all of these heterocycles can be speedily derivatized from resin-bound primary
      amines, incorporating the amines at the 3N-position of quinazoline-2,4-diones or
      corresponding positions of its analogues, it becomes possible to efficiently
      compare the bioactivities of these quinazoline-2,4-diones and their analogues.
      Various methods of solid-phase synthesis described herein should be practical and
      useful tools for the medicinal chemist in supporting drug discovery initiatives.

PMID- 16787371
TI  - Medicinal plants as potential sources of lead compounds with anti-platelet and
      anti-coagulant activities.
AB  - Medicinal plants are potential sources of lead compounds which can be further
      developed or optimised into novel therapeutics. This paper gives an overview of
      drug discovery from plants and an up-to-date and comprehensive review of plants
      and phytoconstituents reported to have anti-platelet and anti-coagulant
      activities.

PMID- 16787373
TI  - 2-(4-aminophenyl) benzothiazole: a potent and selective pharmacophore with novel
      mechanistic action towards various tumour cell lines.
AB  - 2-(4-aminophenyl) benzothiazole (CJM -126) (Table 1 (1) and its analogues
      represent a potent and highly selective class of antitumor agents. These
      compounds in nanomolar range elicit potent growth inhibition in human-derived
      breast, colon, ovarian and renal tumour cell lines. Metabolism of benzothiazole
      plays a central role in its mode of action. Cytocrome P450 isoform, CYP1A1,
      biotransforms benzothiazoles, to active, as well as inactive metabolites. In
      vitro studies had confirmed that N-oxidation and N-acetylation (only 3' halogen
      congener) as main active metabolic transformation (generating cytotoxic
      electrophilic species), while C-6 oxidation and N-acetylation (except 3' halogen
      congener) as inactive metabolic transformation pathway. Generation of an inactive
      metabolite 2-(4-aminophenyl)-6-hydoxybenzothiazole [6-OH 126, (Table 1) (10)] is
      blocked by fluorinated analogue, substituted around benzothiazole nucleus,
      especially at 5-position. National Cancer Institute (NCI), USA, confirms this
      series as a unique mechanistic class distinct from clinically used
      chemotherapeutic agents. Benzothiazoles are potent aryl hydrocarbon receptor
      (AhR) agonists, binding to AhR results in induction of CYP1A1, causes generation
      of electrophilic reactive species which forms DNA adduct, ultimately resulting in
      cell death by activation of apoptotic machinery. To overcome the poor
      physiochemical and pharmaceutical properties (bioavailability problem) of this
      compounds, prodrug of benzothiazole derivatives were synthesized, which are
      introduced in clinical trails.

PMID- 16787374
TI  - Molecular symmetry: a structural property frequently present in new cytotoxic and
      proapoptotic drugs.
AB  - In recent years, a large number of new potent symmetrical cytotoxic agents that
      act through different mechanisms have been described. Apoptosis induction is one
      of the most representative of these mechanisms. Recent articles have revealed
      that the activation of apoptosis pathways is the key mechanism by which cytotoxic
      tumor cells are killed. The present review highlights the importance of the
      molecular symmetry of several chemical structures and their relation with
      cytotoxic and apoptotic activity.

PMID- 16787375
TI  - Adiponectin, structure, function and pathophysiological implications in non
      alcoholic fatty liver disease.
AB  - Obesity is a major risk factor for the development of the metabolic syndrome, a
      cluster of diseases including insulin resistance, type 2 diabetes, dyslipidemia,
      hypertension, microalbuminuria, atherosclerosis, and non-alcoholic
      steatohepatitis. On the other hand, it is now generally accepted that adipose
      tissue acts as an endocrine organ producing a number of substances with an
      important role in the regulation of food intake, energy expenditure and a series
      of metabolic processes. Adiponectin is a recently discovered hormone produced
      exclusively by adipocytes. In fact, adiponectin is considered currently as a
      major factor in obesity-related insulin resistance and atherosclerosis. This new
      hormone differs from other adipocytokines in that its production and
      concentrations are actually decreased in insulin resistant subjects. The aim of
      this review is to summarize the current knowledge about the chemistry and
      physiology of adiponectin and to discuss its implications in the pathophysiology
      and potential treatment of insulin resistance and non-alcoholic fatty liver
      disease.

PMID- 16787376
TI  - Pharmacophore identification: the case of the ser/thr protein phosphatase
      inhibitors.
AB  - This review provides a chronological account of the identification and refinement
      of the pharmacophore for inhibition of two key serine/threonine protein
      phosphatases, PP1 and PP2A. The dramatic impact of natural product isolation,
      molecular modeling, analogue design, biochemical studies, and crystallography on
      the evolution of the pharmacophore will be described.

PMID- 16787377
TI  - The role of vascular endothelial growth factor in neurogenesis in adult brain.
AB  - VEGF is a canonical angiogenic factor. In addition, its role as a stimulator of
      neurogenesis was recently uncovered. Vascular and nervous networks share common
      molecular mechanisms underlying their morphogenesis. VEGF is likely to regulate
      both processes during development and in adult organisms.

PMID- 16787378
TI  - Sphingolipids as targets for microbial infections.
AB  - Sphingolipids had long been regarded as merely structural components of
      eukaryotic cellular membranes. Research has discovered sphingolipids to have
      crucial roles in cellular processes as bioactive molecules. Lately, there has
      also been an increased interest in sphingolipids and sphingolipid-metabolizing
      enzymes as mediators of microbial pathogenicity and as potential targets for the
      development of new therapeutics. This minireview will provide a comprehensive
      analysis of sphingolipid pathways in mammalian and microbial cells, highlighting
      their uniqueness and discussing their potential as therapeutic targets for
      microbial infections.

PMID- 16787379
TI  - SRC inhibitors as potential therapeutic agents for human cancers.
AB  - Selective inhibitors of the Src family of protein tyrosine kinases have been
      developed as therapeutic agents for human tumors, some of which are now in
      various stages of clinical trial. In this review, recently described novel small
      molecule ATP-competitive Src inhibitors are discussed, with an emphasis on their
      potential use as therapeutic inhibitors for advanced-stage malignancies.

PMID- 16787380
TI  - Small molecular weight inhibitors of stress-activated and mitogen-activated
      protein kinases.
AB  - The stress-activated protein kinase (SAPK) and mitogen-activated protein kinase
      (MAPK) sub-families are crucial to environmental stress responses and responses
      to growth factors that cause transcriptional activation of genes required for
      cell proliferation, differentiation and programmed cell death. Small molecular
      compounds with specific structure/activity characteristics have been developed
      that competitively block SAPK/MAPK binding to ATP. Chemically modified compounds
      based on ATP binding pocket characteristics have improved selectivity and
      specificity for SAPK/MAPK isoforms. In addition, site-specific mutagenesis of
      MAPKs has helped identify the MAPK structures required for binding recognition
      and selectivity of these inhibitors. A group of extracellular-signal regulated
      protein kinase (ERK) inhibitors has been constructed based almost exclusively on
      their ability to inhibit the ERK activation cascade. Inhibitors have been
      employed in vitro to identify protein targets and mechanism of action of
      SAPKs/MAPKs. The efficacy of SAPK/MAPK inhibitors in animal models of
      inflammation, arthritis, heart failure, cancer and neurological degeneration has
      provided the impetus for using them in human studies of inflammation and in
      clinical trials.

PMID- 16787381
TI  - Ceramide involvement in apoptosis and apoptotic diseases.
AB  - Apoptosis is implicated in a number of diseases, including neurodegenerative
      diseases and AIDS. More and more, evidence is accumulating pointing to the
      critical role of ceramides in the induction of apoptosis. The present review
      summarizes (i) the molecular basis and regulation of the apoptotic machinery,
      (ii) the molecular role of ceramides in the induction or execution of apoptotic
      pathways, and (iii) evidence linking ceramide generation to various apoptotic
      diseases. Additionally, this review discusses putative therapeutic approaches
      inhibiting ceramide production in apoptotic diseases.

PMID- 16787382
TI  - Recent progress in development of non-ATP competitive small-molecule inhibitors
      of protein kinases.
AB  - The majority of marketed and late stage development kinase inhibitors are
      reported to be ATP-competitive. As a result, many promising drug candidates
      display non-specific activity that results in undesired physiological effects.
      There is growing interest towards non-ATP competitive kinase inhibitors, as they
      are expected to yield highly specific and efficacious molecules devoid of non
      mechanistic toxicity. Recent developments in this area are summarized in our
      review.

PMID- 16787383
TI  - Mechanisms of action and targets for actual and future antiplatelet drugs.
AB  - Platelets are key players in arterial thrombosis and have become important
      targets in the primary and secondary prevention of atherothrombosis. Antiplatelet
      drugs are primarily directed against platelets and inhibit platelet activation by
      a number of different mechanisms. They are used for the prevention and treatment
      of thrombotic processes, especially in the arterial vascular system. Antiplatelet
      drugs in clinical use and experimental drugs are discussed.

PMID- 16787384
TI  - HIV-1 RNase H: recent progress in an exciting, yet little explored, drug target.
AB  - HIV-1 reverse transcriptase-associated ribonuclease H (RNase H) is an attractive
      non traditional target for drug development which has been, so far, little
      explored. All drugs shown to inhibit HIV-1 RNase H are reported, including the
      recently described classes of compounds that interact with the metal ions in the
      active site.

PMID- 16787385
TI  - Regulation of GLUT4 gene expression by SREBP-1c in adipocytes.
AB  - Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes
      is subject to hormonal or metabolic control. In the present study, we have
      characterized an adipose tissue transcription factor that is influenced by
      fasting/refeeding regimens and insulin. Northern blotting showed that refeeding
      increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an
      increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory
      element-binding protein)-1c in adipose tissue were also increased by refeeding.
      In streptozotocin-induced diabetic rats, insulin treatment increased the mRNA
      levels of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays
      and electrophoretic mobility-shift assay studies indicated that the putative
      sterol response element is located in the region between bases -109 and -100 of
      the human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to
      differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4,
      suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin
      immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to
      the putative sterol-response element in the GLUT4. Furthermore, treating
      streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In
      addition, we have identified an Sp1 binding site adjacent to the functional
      sterol-response element in the GLUT4 promoter. The Sp1 site appears to play an
      additive role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest
      that upregulation of GLUT4 gene transcription might be directly mediated by SREBP
      1c in adipose tissue.

PMID- 16787386
TI  - Zymosan-induced glycerylprostaglandin and prostaglandin synthesis in resident
      peritoneal macrophages: roles of cyclo-oxygenase-1 and -2.
AB  - COX [cyclo-oxygenase; PG (prostaglandin) G/H synthase] oxygenates AA (arachidonic
      acid) and 2-AG (2-arachidonylglycerol) to endoperoxides that are converted into
      PGs and PG-Gs (glycerylprostaglandins) respectively. In vitro, 2-AG is a
      selective substrate for COX-2, but in zymosan-stimulated peritoneal macrophages,
      PG-G synthesis is not sensitive to selective COX-2 inhibition. This suggests that
      COX-1 oxygenates 2-AG, so studies were carried out to identify enzymes involved
      in zymosan-dependent PG-G and PG synthesis. When macrophages from COX-1-/- or COX
      2-/- mice were treated with zymosan, 20-25% and 10-15% of the PG and PG-G
      synthesis observed in wild-type cells respectively was COX-2 dependent. When
      exogenous AA and 2-AG were supplied to COX-2-/- macrophages, PG and PG-G
      synthesis was reduced as compared with wild-type cells. In contrast, when
      exogenous substrates were provided to COX-1-/- macrophages, PG-G but not PG
      synthesis was reduced. Product synthesis also was evaluated in macrophages from
      cPLA(2alpha) (cytosolic phospholipase A2alpha)-/- mice, in which zymosan-induced
      PG synthesis was markedly reduced, and PG-G synthesis was increased approx. 2
      fold. These studies confirm that peritoneal macrophages synthesize PG-Gs in
      response to zymosan, but that this process is primarily COX-1-dependent, as is
      the synthesis of PGs. They also indicate that the 2-AG and AA used for PG-G and
      PG synthesis respectively are derived from independent pathways.

PMID- 16787388
TI  - Conformational stability of human frataxin and effect of Friedreich's ataxia
      related mutations on protein folding.
AB  - The neurodegenerative disorder FRDA (Friedreich's ataxia) results from a
      deficiency in frataxin, a putative iron chaperone, and is due to the presence of
      a high number of GAA repeats in the coding regions of both alleles of the
      frataxin gene, which impair protein expression. However, some FRDA patients are
      heterozygous for this triplet expansion and contain a deleterious point mutation
      on the other allele. In the present study, we investigated whether two particular
      FRDA-associated frataxin mutants, I154F and W155R, result in unfolded protein as
      a consequence of a severe structural modification. A detailed comparison of the
      conformational properties of the wild-type and mutant proteins combining
      biophysical and biochemical methodologies was undertaken. We show that the FRDA
      mutants retain the native fold under physiological conditions, but are
      differentially destabilized as reflected both by their reduced thermodynamic
      stability and a higher tendency towards proteolytic digestion. The I154F mutant
      has the strongest effect on fold stability as expected from the fact that the
      mutated residue contributes to the hydrophobic core formation. Functionally, the
      iron-binding properties of the mutant frataxins are found to be partly impaired.
      The apparently paradoxical situation of having clinically aggressive frataxin
      variants which are folded and are only significantly less stable than the wild
      type form in a given adverse physiological stress condition is discussed and
      contextualized in terms of a mechanism determining the pathology of FRDA
      heterozygous.

PMID- 16787387
TI  - Comparative functional analysis of human medium-chain dehydrogenases, short-chain
      dehydrogenases/reductases and aldo-keto reductases with retinoids.
AB  - Retinoic acid biosynthesis in vertebrates occurs in two consecutive steps: the
      oxidation of retinol to retinaldehyde followed by the oxidation of retinaldehyde
      to retinoic acid. Enzymes of the MDR (medium-chain dehydrogenase/reductase), SDR
      (short-chain dehydrogenase/reductase) and AKR (aldo-keto reductase) superfamilies
      have been reported to catalyse the conversion between retinol and retinaldehyde.
      Estimation of the relative contribution of enzymes of each type was difficult
      since kinetics were performed with different methodologies, but SDRs would
      supposedly play a major role because of their low K(m) values, and because they
      were found to be active with retinol bound to CRBPI (cellular retinol binding
      protein type I). In the present study we employed detergent-free assays and HPLC
      based methodology to characterize side-by-side the retinoid-converting activities
      of human MDR [ADH (alcohol dehydrogenase) 1B2 and ADH4), SDR (RoDH (retinol
      dehydrogenase)-4 and RDH11] and AKR (AKR1B1 and AKR1B10) enzymes. Our results
      demonstrate that none of the enzymes, including the SDR members, are active with
      CRBPI-bound retinoids, which questions the previously suggested role of CRBPI as
      a retinol supplier in the retinoic acid synthesis pathway. The members of all
      three superfamilies exhibit similar and low K(m) values for retinoids (0.12-1.1
      microM), whilst they strongly differ in their kcat values, which range from 0.35
      min(-1) for AKR1B1 to 302 min(-1) for ADH4. ADHs appear to be more effective
      retinol dehydrogenases than SDRs because of their higher kcat values, whereas
      RDH11 and AKR1B10 are efficient retinaldehyde reductases. Cell culture studies
      support a role for RoDH-4 as a retinol dehydrogenase and for AKR1B1 as a
      retinaldehyde reductase in vivo.

PMID- 16787389
TI  - Cleavage in the GDPH sequence of the C-terminal cysteine-rich part of the human
      MUC5AC mucin.
AB  - MUC5AC is the main gel-forming mucin expressed by goblet cells of the airways and
      stomach where it protects the underlying epithelia. We expressed the C-terminal
      cysteine-rich part of the human MUC5AC mucin in CHO-K1 cells (Chinese-hamster
      ovary K1 cells) where it formed disulfide-linked dimers in the ER (endoplasmic
      reticulum). After reducing the disulfide bonds of these dimers, not only the
      expected monomers were found, but also two smaller fragments, indicating that the
      protein was partially cleaved. The site of cleavage was located at an Asp-Pro
      bond situated in a GDPH (Gly-Asp-Pro-His) sequence found in the vWD4 (von
      Willebrand D4) domain. This sequence is also found in the human MUC2 mucin,
      previously shown to be cleaved at the same site by a slow, non-enzymatic process
      triggered by a pH below 6 [Lidell, Johansson and Hansson (2003) J. Biol. Chem.
      278, 13944-13951]. In contrast with this, the cleavage of MUC5AC started already
      in the neutral ER. However, it continued and was slightly accelerated at a pH
      below 6.5, a pH found in the later parts of the secretory pathway. The cleavage
      generated a reactive group in the new C-terminus that could link the protein to a
      primary amine. No cleavage of MUC5AC has so far been reported. By using an
      antibody reacting with the C-terminal cleavage fragment, we could verify that the
      cleavage occurs in wild-type MUC5AC produced by HT-29 cells. The cleavage of
      MUC5AC and the generation of the reactive new C-terminus could contribute to the
      adherent and viscous mucus found at chronic lung diseases such as asthma and
      cystic fibrosis, characterized by mucus hypersecretion and lowered pH of the
      airways.

PMID- 16787390
TI  - Age-related accumulation of pentosidine in aggrecan and collagen from normal and
      degenerate human intervertebral discs.
AB  - During aging and degeneration, many changes occur in the structure and
      composition of human cartilaginous tissues, which include the accumulation of the
      AGE (advanced glycation end-product), pentosidine, in long-lived proteins. In the
      present study, we investigated the accumulation of pentosidine in constituents of
      the human IVD (intervertebral disc), i.e. collagen, aggrecan-derived PG
      (proteoglycan) (A1) and its fractions (A1D1-A1D6) in health and pathology. We
      found that, after maturity, pentosidine accumulates with age. Over the age range
      studied, a linear 6-fold increase was observed in pentosidine accumulation for A1
      and collagen with respective rates of 0.12 and 0.66 nmol x (g of protein)(-1) x
      year(-1). Using previously reported protein turnover rate constants (k(T))
      obtained from measurements of the D-isomer of aspartic residue in collagen and
      aggrecan of human IVD, we could calculate the pentosidine formation rate
      constants (k(F)) for these constituents [Sivan, Tsitron, Wachtel, Roughley,
      Sakkee, van der Ham, DeGroot, Roberts and Maroudas (2006) J. Biol. Chem. 281,
      13009-13014; Tsitron (2006) MSc Thesis, Technion-Israel Institute of Technology,
      Haifa, Israel]. In spite of the comparable formation rate constants obtained for
      A1D1 and collagen [1.81+/-0.25 compared with 3.71+/-0.26 micromol of pentosidine
      x (mol of lysine)(-1) x year(-1) respectively], the higher pentosidine
      accumulation in collagen is consistent with its slower turnover (0.005 year(-1)
      compared with 0.134 year(-1) for A1D1). Pentosidine accumulation increased with
      decreasing buoyant density and decreasing turnover of the proteins from the most
      glycosaminoglycan-rich PG components (A1D1) to the least (A1D6), with respective
      k(F) values of 1.81+/-0.25 and 3.18+/-0.37 micromol of pentosidine.(mol of
      lysine)(-1) x year(-1). We concluded that protein turnover is an important
      determinant of pentosidine accumulation in aggrecan and collagen of human IVD, as
      was found for articular cartilage. Correlation of pentosidine accumulation with
      protein half-life in both normal and degenerate discs further supports this
      finding.

PMID- 16787392
TI  - Toward the systems biology of vesicle transport.
AB  - Systems biology aims to study complex biological processes, such as intracellular
      traffic, as a whole. Systematic genome-wide assays have the potential to identify
      the transport machinery, delineate pathways and uncover the molecular components
      of physiological processes that influence trafficking. A goal of this approach is
      to create predictive models of intracellular trafficking pathways that reflect
      these relationships. In this review, we highlight current genome-wide
      technologies of particular relevance to vesicle transport and describe recent
      applications of these technologies in the framework of systems biology. Systems
      approaches hold great promise for placing trafficking pathways in their cellular
      contexts.

PMID- 16787391
TI  - Cloning of rat amelotin and localization of the protein to the basal lamina of
      maturation stage ameloblasts and junctional epithelium.
AB  - Formation of tooth enamel is a very complex process in which a specific set of
      proteins secreted by ameloblasts play a primordial role. As part of a screening
      procedure to identify novel proteins secreted by EO (enamel organ) cells of rat
      incisors, we isolated a partial cDNA fragment (EO-017) that is the homologue of
      the recently described mouse Amtn (amelotin) gene [Iwasaki, Bajenova, Somogyi
      Ganss, Miller, Nguyen, Nourkeyhani, Gao, Wendel and Ganss (2005) J. Dent. Res.
      84, 1127-1132]. Presented herein is the cloning of rat and pig full-length cDNAs
      with their deduced protein sequences. Detailed expression profiling by Northern
      blot analysis and RT (reverse transcriptase)-PCR on rat and mouse tissues
      revealed highest expression in the mandible, more specifically in the maturation
      stage of the EO. Among all tissues tested, low expression was detected only in
      periodontal ligament, lung, thymus and gingiva. In silico analyses revealed that
      the Amtn gene is highly conserved in seven other mammals, but is absent from
      fish, birds and amphibians. The Amtn protein is enriched in proline, leucine,
      glutamine and threonine (52% of total) and contains a perfectly conserved protein
      kinase CK2 phosphorylation site. Transient transfection experiments in HEK-293
      cells (human embryonic kidney cells) showed that secreted Amtn is post
      translationally modified possibly through O-linked oligosaccharides on threonine
      residues. In concordance with its predominant expression site, immunofluorescence
      localization within the rat and mouse mandibles revealed Amtn localized to the
      basal lamina of maturation stage ameloblasts of incisors and unerupted molars.
      Intense Amtn protein expression was also detected in the internal basal lamina of
      junctional epithelium in molars. The peculiar and unique cellular localization of
      Amtn suggests a role in cell adhesion.

PMID- 16787393
TI  - The quest for the mechanism of melanin transfer.
AB  - Skin pigmentation is accomplished by production of melanin in specialized
      membrane-bound organelles termed melanosomes and by transfer of these organelles
      from melanocytes to surrounding keratinocytes. The mechanism by which these cells
      transfer melanin is yet unknown. A central role has been established for the
      protease-activated receptor-2 of the keratinocyte which effectuates melanin
      transfer via phagocytosis. What exactly is being phagocytosed - naked melanin,
      melanosomes or melanocytic cell parts - remains to be defined. Analogy of
      melanocytes to neuronal cells and cells of the haemopoietic lineage suggests
      exocytosis of melanosomes and subsequent phagocytosis of naked melanin.
      Otherwise, microscopy studies demonstrate cytophagocytosis of melanocytic
      dendrites. Other plausible mechanisms are transfer via melanosome-containing
      vesicles shed by the melanocyte or transfer via fusion of keratinocyte and
      melanocyte plasma membranes with formation of tunnelling nanotubes. Molecules
      involved in transfer are being identified. Transfer is influenced by the
      interactions of lectins and glycoproteins and, probably, by the action of E
      cadherin, SNAREs, Rab and Rho GTPases. Further clues as to what mechanism and
      molecular machinery will arise with the identification of the function of
      specific genes which are mutated in diseases that affect transfer.

PMID- 16787395
TI  - Alpha-sarcoglycan is recycled from the plasma membrane in the absence of
      sarcoglycan complex assembly.
AB  - The sarcoglycan complex consists of four subunits in skeletal muscle (alpha,
      beta, gamma, and delta-SG). Mutations in alpha-sarcoglycan (alpha-SG) result in
      the most common form of limb girdle muscular dystrophy. However, the function of
      alpha-SG remains unknown. In this report we attempt to clarify its function by
      delineating the trafficking pathway of alpha-SG in live cells. We present
      evidence, utilizing total internal reflection microscopy, fluorescence recovery
      after photobleaching and photoactivation of green fluorescent protein (GFP)
      constructs, that pools of alpha-SG are able to translocate to the plasma membrane
      in the absence of the remaining sarcoglycans. Internalization assays and drug
      treatment experiments demonstrate that alpha-SG recycles from the plasma membrane
      and accumulates in recycling endosomes. We also establish that alpha-SG utilizes
      well-described clathrin mediated mechanisms and microtubules to traffic within
      the cell. Finally, we show that the most commonly reoccurring limb girdle
      muscular dystrophy (R77C) mutation causes a fundamental defect in protein
      biosynthesis, trapping the mutant protein in the endoplasmic recticulum (ER).
      These results demonstrate that alpha-SG requires assembly into the sarcoglycan
      complex for stability at the plasma membrane rather than export out of the ER.
      Furthermore, this data suggests that alpha-SG utilizes known trafficking
      machinery to control deposition at the plasma membrane through recycling.

PMID- 16787394
TI  - Interaction of Hermansky-Pudlak Syndrome genes in the regulation of lysosome
      related organelles.
AB  - Hermansky-Pudlak Syndrome (HPS) is a genetically heterogeneous disease caused by
      abnormalities in the synthesis and/or trafficking of lysosome-related organelles
      (LROs) including melanosomes, lamellar bodies of lung type II cells and platelet
      dense granules. At least 15 genes cause HPS in mice, with a significant number
      specifying novel subunits of protein complexes termed BLOCs (Biogenesis of
      Lysosome-related Organelles Complexes). To ascertain whether BLOC complexes
      functionally interact in vivo, mutant mice doubly or triply deficient in protein
      subunits of the various BLOC complexes and/or the AP-3 adaptor complex were
      constructed and tested for viability and for abnormalities of melanosomes, lung
      lamellar bodies and lysosomes. All mutants, including those deficient in all
      three BLOC complexes, were viable though the breeding efficiencies of multiple
      mutants involving AP-3 were severely compromised. Interactions of BLOC protein
      complexes with each other and with AP-3 to affect most LROs were apparent.
      However, these interactions were tissue and organelle dependent. These studies
      document novel biological interactions of BLOC and AP-3 complexes in the
      biosynthesis of LROs and assess the role(s) of HPS protein complexes in general
      health and physiology in mammals. Double and triple mutant HPS mice provide
      unique and practical experimental advantages in the study of LROs.

PMID- 16787396
TI  - Dynamin is involved in endolysosomal cholesterol delivery to the endoplasmic
      reticulum: role in cholesterol homeostasis.
AB  - Cholesterol is one of the most essential membrane components in mammalian cells
      and plays a critical role in several cellular functions. It is now established
      that intracellular cholesterol transport contributes to the regulation of
      cellular cholesterol homeostasis by mechanisms that are yet poorly defined. In
      this study, we examined the role of clathrin- and dynamin-dependent trafficking
      on the regulatory machinery involved in cholesterol homeostasis. Thus, expression
      levels of three major sterol-sensitive genes, that is sterol-regulatory element
      binding protein 2 (SREBP-2), hydroxymethylglutaryl-coenzyme A (HMGCoA) reductase
      and low-density lipoprotein (LDL) receptor, were monitored to study the cell
      response to the addition of LDL-derived cholesterol. We found that inhibition of
      clathrin-dependent endocytosis had no effect on the intracellular distribution of
      cholesterol and the regulation of sterol-sensitive genes. In contrast, inhibition
      of dynamin activity resulted in the lack of regulation of SREBP-2, HMGCoA
      reductase and LDL receptor genes. Immunolocalization studies along with the
      measure of free and esterified cholesterol indicated that dynamin inactivation
      led to the accumulation of free cholesterol (FC) within the late endosomal
      (LE)/lysosomal compartment resulting in insufficient delivery of regulatory
      cholesterol to the endoplasmic reticulum (ER) where the transcriptional control
      of sterol-sensitive genes occurs. Our data therefore indicate that dynamin plays
      a critical role in the delivery of cholesterol from the LE/lysosomal network to
      the ER and highlight the importance of LE trafficking in cholesterol homeostasis.

PMID- 16787397
TI  - Measles virus contact with T cells impedes cytoskeletal remodeling associated
      with spreading, polarization, and CD3 clustering.
AB  - CD3/CD28-induced activation of the PI3/Akt kinase pathway and proliferation is
      impaired in T cells after contact with the measles virus (MV) glycoprotein (gp)
      complex. We now show that this signal also impairs actin cytoskeletal remodeling
      in T cells, which loose their ability to adhere and to promote microvilli
      formation. MV exposure results in an almost complete collapse of membrane
      protrusions associated with reduced phosphorylation levels of cofilin and
      ezrin/radixin/moesin (ERM) proteins. Consistent with their inability to activate
      Cdc42 and Rac1 in response to the ligation of CD3/CD28, T cells exposed to MV
      fail to acquire a morphology consistent with spreading and lamellopodia
      formation. In spite of these impairments of cytoskeleton-driven morphological
      alterations, these cells are recruited into conjugates with dendritic cells as
      efficiently as control T cells. The signal elicited by MV, however, prevents T
      cells to polarize as documented by a failure to redistribute the microtubule
      organizing center toward the synapse. Moreover, CD3 cannot be efficiently
      clustered and redistributed to the central region of the immunological synapse.
      Thus, by inducing microvillar collapse and interfering with cytoskeletal
      remodeling, MV signaling disturbs the ability of T cells to adhere, spread, and
      cluster receptors essential for sustained T-cell activation.

PMID- 16787398
TI  - Contributions of intracellular compartments to calcium dynamics: implicating an
      acidic store.
AB  - Many cells show a plateau of elevated cytosolic Ca(2+) after a long
      depolarization, suggesting delayed Ca(2+) release from intracellular compartments
      such as mitochondria and endoplasmic reticulum (ER). Mouse pancreatic beta-cells
      show a thapsigargin-sensitive plateau ('hump') of Ca(2+) after a 30 s
      depolarization but not after a 10 s depolarization. Surprisingly, this hump
      depends primarily on compartments other than the mitochondria or ER. It is
      reduced by only 22% upon blocking mitochondrial Na(+)-Ca(2+) exchange and by only
      18% upon blocking ryanodine or IP(3) receptors together. Further, the time course
      of ER Ca(2+) measured by a targeted cameleon does not depend on the duration of
      depolarizations. Instead, the hump is reduced 35% by treatments with the
      dipeptide glycylphenylalanine beta-napthylamide, a tool often used to lyse
      lysosomes. We show that this dipeptide does not disturb ER functions, but it
      lyses acidic compartments and releases Ca(2+) into the cytosol. Moreover, it
      induces leaks in and possibly lyses insulin granules and stops mobilization of
      secretory granules to the readily releasable pool in beta-cells. We conclude that
      the dipeptide compromises dense-core secretory granules and that these granules
      comprise an acidic calcium store in beta-cells whose loading and/or release is
      sensitive to thapsigargin and which releases Ca(2+) after cytosolic Ca(2+)
      elevation.

PMID- 16787399
TI  - The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and
      mannose 6-phosphate receptor.
AB  - Acid sphingomyelinase (ASM), a member of the saposin-like protein (SAPLIP)
      family, is a lysosomal hydrolase that converts sphingomyelin to ceramide.
      Deficiency of ASM causes a variant form of Niemann-Pick disease. The mechanism of
      lysosomal targeting of ASM is poorly known. Previous studies suggest that ASM
      could use in part the mannose 6-phosphate receptor (M6P-Rc). Sortilin, a type I
      transmembrane glycoprotein that belongs to a novel family of receptor proteins,
      presents structural features of receptors involved in lysosomal targeting. In
      this study we examined the hypothesis that sortilin may be implicated in the
      trafficking of ASM to the lysosomes. Using a dominant-negative sortilin construct
      lacking the cytoplasmic tail, which is essential to recruit adaptor proteins and
      clathrin, we demonstrated that sortilin is also involved in the lysosomal
      targeting of ASM. Confocal microscopy revealed that truncated sortilin partially
      inhibited the lysosomal trafficking of ASM in COS-7 cells and abolished the
      lysosomal targeting of ASM in I-cells. Pulse-chase experiments corroborated that
      sortilin is involved in normal sorting of newly synthesized ASM. Furthermore,
      over-expression of truncated sortilin accelerated and enhanced the secretion of
      ASM from COS-7 cells and I-cells. Co-immunoprecipitation assays confirmed the
      interaction between sortilin and ASM. In conclusion, ASM uses sortilin as an
      alternative receptor to be targeted to the lysosomes.

PMID- 16787400
TI  - Cyclodextrins but not compactin inhibit the lateral diffusion of membrane
      proteins independent of cholesterol.
AB  - Cholesterol and glycosphingolipid-enriched membrane domains, termed lipid rafts,
      were proposed to play important roles in trafficking and signaling events. These
      functions are inhibited following putative disruption of rafts by cholesterol
      depletion, commonly induced by treatment with methyl-beta-cyclodextrin (MbetaCD).
      However, several studies showed that the lateral diffusion of membrane proteins
      is inhibited by MbetaCD, suggesting that it may have additional effects on
      membrane organization unrelated to cholesterol removal. Here, we investigated
      this possibility by comparison of the effects of cholesterol depletion by MbetaCD
      and by metabolic inhibition (compactin), and of treatment with alpha-CD, which
      does not bind cholesterol. The studies employed two series of proteins (Ras and
      influenza hemagglutinin), each containing as internal controls related mutants
      that differ in raft association. Mild MbetaCD treatment retarded the lateral
      diffusion of both raft and non-raft mutants, whereas similar cholesterol
      reduction (30-33%) by metabolic inhibition enhanced selectively the diffusion of
      the raft-associated mutants. Moreover, alpha-CD also inhibited the diffusion of
      raft and non-raft mutants, despite its lack of effect on cholesterol content.
      These findings suggest that the widely used treatment with CD to reduce
      cholesterol has additional, cholesterol-independent effects on membrane protein
      mobility, which do not necessarily distinguish between raft and non-raft
      proteins.

PMID- 16787401
TI  - Intrinsic and extrinsic determinants of ion channel localization in neurons.
AB  - Neurons are an extremely diverse group of excitable cells with a wide variety of
      morphologies including complex dendritic trees and very long axons. The
      electrical properties of neurons depend not only on the types of ion channels and
      receptors expressed, but also on where these channels are located in the cell.
      Two extreme examples that illustrate the subcellular polarized nature of neurons
      and the tight regulation of ion channel localization can be seen at the axon
      initial segment and the node of Ranvier. The axon initial segment is important
      for initiation of action potentials in the axon, whereas the node of Ranvier is
      required for the rapid, faithful and efficient propagation of action potentials
      along the axon. Given the similarity of their functions it is not surprising that
      nearly every protein component of the axon initial segment is also found at the
      node. However, there is one very important difference between these two sites:
      nodes require extrinsic, glial-derived factors in order to form, whereas the axon
      initial segment is intrinsically determined by the neuron. This mini-review
      discusses recent results that have begun to clarify the intrinsic and extrinsic
      mechanisms underlying formation of nodes and axon initial segments, and poses
      several important unanswered questions regarding their unique mechanisms of
      formation.

PMID- 16787402
TI  - Genetic vitamin E deficiency does not affect MPTP susceptibility in the mouse
      brain.
AB  - Oxidative stress is involved in the degeneration of the nigrostriatal
      dopaminergic system in Parkinson's disease (PD). Vitamin E (alpha-tocopherol) is
      a potent antioxidant in the cell membrane that can trap free radicals and
      prohibit lipid peroxidation. The retention and secretion of vitamin E are
      regulated by alpha-tocopherol transfer protein (TTP) in the brain and liver.
      Dysfunction of TTP results in systemic deficiency of vitamin E in humans and
      mice, and increased oxidative stress in mouse brain. In this study, we
      investigated the effect of vitamin E deficiency in PD development by generating
      an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD using
      TTP knockout (TTP-/-) mice. Vitamin E concentration in the brains of TTP+/- mice
      was half that in TTP+/+ mice, and in TTP-/- mice, was undetectable. MPTP
      treatment tended to decrease striatal dopamine, but the effect was comparable and
      not significant in any of the three genotypes. Furthermore, the extent of loss of
      dopaminergic cell bodies in the substantia nigra did not differ among the groups.
      One the other hand, oral administration of vitamin E resulted in the partial
      protection of striatal dopaminergic terminals against MPTP toxicity. Our results
      suggest that vitamin E does not play a major protective role in MPTP-induced
      nigrostriatal dopaminergic neurodegeneration in the brain.

PMID- 16787403
TI  - Calsenilin interacts with transcriptional co-repressor C-terminal binding
      protein(s).
AB  - Calsenilin/potassium channel-interacting protein (KChIP)3/ downstream regulatory
      element sequence antagonist modulator (DREAM) is a neuronal calcium-binding
      protein that has been shown to have multiple functions in the cell, including the
      regulation of presenilin processing, repression of transcription and modulation
      of A-type potassium channels. To gain a better understanding of the precise role
      of calsenilin in specific cellular compartments, an interactor hunt for proteins
      that bind to the N-terminal domain of calsenilin was carried out. Using a yeast
      two-hybrid system and co-immunoprecipitation studies, we have identified the
      transcriptional co-repressor C-terminal binding protein (CtBP)2 as an interactor
      for calsenilin and have shown that the two proteins can interact in vivo. In co
      immunoprecipitation studies, calsenilin also interacted with CtBP1, a CtBP2
      homolog. Our data also showed a calsenilin-dependent increase in c-fos protein
      levels in CtBP knockout fibroblasts, suggesting that CtBP may modulate the
      transcriptional repression of c-fos by calsenilin. Furthermore, the finding that
      histone deacetylase protein and activity were associated with the calsenilin-CtBP
      immunocomplex suggests a mechanism by which calsenilin-CtBP may act to repress
      transcription. Finally, we demonstrated that calsenilin and CtBP are present in
      synaptic vesicles and can interact in vivo.

PMID- 16787404
TI  - The transcription factor DeltaFosB is recruited by inflammatory pain.
AB  - DeltaFosB, a stable splice variant of FosB, has been proposed to mediate
      persistent brain adaptation in response to several chronic perturbations, but it
      has not yet been considered in the context of sustained pain. Inflammatory pain
      induces neuronal plasticity that can result in persistent alteration of
      nociceptive pathways. This neuronal plasticity can partly result from changes in
      gene expression controlled by transcription factors. In the present study, we
      analyse the capacity of carrageenan-mediated inflammation to induce DeltaFosB in
      the spinal cord. We found that hind-paw inflammation increases FosB-like
      immunoreactivity in the superficial layers of rat lumbar spinal cord for at least
      7 days. This induction parallels mechanical hyperalgesia and is maximal in the
      dorsal horn of segment L4 of the spinal cord which corresponds to the primary
      nociceptive afferent regions from the hind paw. We identified this FosB-like
      signal as DeltaFosB by comparing data obtained with antibodies raised against
      either an epitope present in both FosB and DeltaFosB, or the FosB C-terminal
      region that is deleted in DeltaFosB. The week-lasting changes in DeltaFosB
      highlight the interest in this protein as a molecular marker of sustained pain,
      and suggest a role of this transcription factor in pain-related plasticity within
      the spinal cord.

PMID- 16787405
TI  - Calpain product of WT-CRMP2 reduces the amount of surface NR2B NMDA receptor
      subunit.
AB  - The brain is particularly vulnerable to ischaemia; however, neurons can become
      tolerant to ischaemic insult. This tolerance has been shown to involve activation
      of NMDA receptors, but its mechanisms have not yet been fully elucidated. Using a
      preconditioning protocol, we show that neurons surviving to a transient NMDA
      exposure become resistant to the glutamatergic agonist. Using a proteomic
      approach, we found that alterations of the protein pattern of NMDA-resistant
      neurons are restricted mainly to the five collapsin response mediator proteins
      (CRMPs). A sustained increase in calpain activity following NMDA treatment is
      responsible for the production of cleaved CRMPs. Finally, we provide evidence for
      the involvement of the cleaved form of WT-CRMP2 in the down-regulation of NR2B.
      Our data suggests that, beside their role in neuronal morphogenesis, CRMPs may
      contribute to neuronal plasticity.

PMID- 16787406
TI  - Inhibition of 26S proteasome activity by huntingtin filaments but not inclusion
      bodies isolated from mouse and human brain.
AB  - In Huntington's disease (HD), as in the rest of CAG triplet-repeat disorders, the
      expanded polyglutamine (polyQ)-containing proteins form intraneuronal fibrillar
      aggregates that are gathered into inclusion bodies (IBs). Since IBs contain
      ubiquitin and proteasome subunits, it was proposed that inhibition of proteasome
      activity might underlie pathogenesis of polyQ disorders. Recent in vitro
      enzymatic studies revealed the inability of eukaryotic proteasomes to digest
      expanded polyQ, thus suggesting that occasional failure of polyQ to exit the
      proteasome may interfere with its proteolytic function. However, it has also
      recently been found that in vitro assembled aggregates made of synthetic polyQ
      fail to inhibit proteasome activity. Because synthetic polyQ aggregates lack the
      post-translational modifications found inside affected neurons, such as poly
      ubiquitylation, we decided to study the effect of mutant huntingtin (htt)
      aggregates isolated from the Tet/HD94 mouse model and from human HD brain tissue.
      Here, we show that isolated ubiquitylated filamentous htt aggregates, extracted
      from IBs by a previously reported method, selectively inhibited the in vitro
      peptidase activity of the 26S but not of the 20S proteasome in a non-competitive
      manner. In good agreement, immuno-electron microscopy revealed a direct
      interaction of htt filaments with the 19S ubiquitin-interacting regulatory caps
      of the 26S proteasome. Here, we also report a new method for isolation of IBs
      based on magnetic sorting. Interestingly, isolated IBs did not modify proteasome
      activity. Our results therefore show that mutant htt filamentous aggregates can
      inhibit proteasome activity, but only when not recruited into IBs, thus
      strengthening the notion that IB formation is protective by neutralizing toxicity
      of dispersed filamentous htt aggregates.

PMID- 16787407
TI  - RS-alpha-lipoic acid protects cholinergic cells against sodium nitroprusside and
      amyloid-beta neurotoxicity through restoration of acetyl-CoA level.
AB  - The work presented here verifies the hypothesis that RS-alpha-lipoic acid may
      exert its cholinoprotective and cholinotrophic activities through the maintenance
      of appropriate levels of acetyl-CoA in mitochondrial and cytoplasmic compartments
      of cholinergic neurons. Sodium nitroprusside (SNP) and amyloid-beta decreased
      pyruvate dehydrogenase, choline acetyltransferase activities, acetyl-CoA content
      in mitochondria and cytoplasm, as well as increased fraction of non-viable,
      trypan blue positive cells in cultured differentiated cholinergic SN56
      neuroblastoma cells. Lipoic acid totally reversed toxin-evoked suppression of
      choline acetyltrasferase and pyruvate dehydrogenase activities, as well as
      mitochondrial and cytoplasmic acetyl-CoA levels, and partially attenuated
      increase of cell mortality. Significant negative correlations were found between
      enzyme activities, acetyl-CoA levels and cell mortality in different neurotoxic
      and neuroprotective conditions employed here. The level of cytoplamic acetyl-CoA
      correlated with mitochondrial acetyl-CoA, whereas choline acetyltransferase
      activity followed shifts in cytoplasmic acetyl-CoA. Thus, we conclude that, in
      cholinergic neurons, particular elements of the pyruvate-acetyl-CoA-acetylcholine
      pathway form a functional unit responding uniformly to nerotoxic and
      neuroprotectory conditions.

PMID- 16787408
TI  - Hypoxic damage to the periventricular white matter in neonatal brain: role of
      vascular endothelial growth factor, nitric oxide and excitotoxicity.
AB  - The present study examined factors that may be involved in the development of
      hypoxic periventricular white matter damage in the neonatal brain. Wistar rats (1
      day old) were subjected to hypoxia and the periventricular white matter (corpus
      callosum) was examined for the mRNA and protein expression of hypoxia-inducible
      factor-1alpha (HIF-1alpha), endothelial, neuronal and inducible nitric oxide
      synthase (eNOS, nNOS and iNOS), vascular endothelial growth factor (VEGF) and N
      methyl-D-aspartate receptor subunit 1 (NMDAR1) between 3 h and 14 days after
      hypoxic exposure by real-time RT-PCR, western blotting and immunohistochemistry.
      Up-regulated mRNA and protein expression of HIF-1alpha, VEGF, NMDAR1, eNOS, nNOS
      and iNOS in corpus callosum was observed in response to hypoxia. NMDAR1 and iNOS
      expression was found in the activated microglial cells, whereas VEGF was
      localized to astrocytes. An enzyme immunoassay showed that the VEGF concentration
      in corpus callosum was significantly higher up to 7 days after hypoxic exposure.
      NO levels, measured by colorimetric assay, were also significantly higher in
      hypoxic rats up to 14 days after hypoxic exposure as compared with the controls.
      A large number of axons undergoing degeneration were observed between 3 h and 7
      days after the hypoxic exposure at electron-microscopic level. Our findings point
      towards the involvement of excitotoxicity, VEGF and NO in periventricular white
      matter damage in response to hypoxia.

PMID- 16787409
TI  - Cycloheximide treatment to identify components of the transitional transcriptome
      in PACAP-induced PC12 cell differentiation.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neurite
      outgrowth, reduces proliferation and inhibits apoptosis of PC12 cells. We have
      partially characterized the transcriptome changes induced by PACAP after 6 h of
      treatment, when commitment to differentiation has occurred. Here, we have
      investigated the effects of a 6-h treatment with PACAP (10(-7) m) in the presence
      of cycloheximide (5 microm) to identify, via superinduction, components of the
      transitional transcriptome initially induced by PACAP and potentially
      participating in the regulation of late-response genes required for
      differentiation. Approximately 100 new transcripts were identified in this
      screen, i.e. as many individual genes as make up the 6-h PACAP differentiation
      transcriptome itself. Six known transcripts in this cohort were then measured at
      several time points between 0 and 6 h by real-time PCR to determine whether these
      transcripts are induced early following PACAP treatment in the absence of
      cycloheximide, and therefore may be of functional importance in differentiation.
      Five out of the six transcripts were indeed induced by PACAP alone soon (between
      30 min and 3 h) after cell treatment. beta-Cell translocation gene 2,
      antiproliferative (Btg2), serum/glucocorticoid-regulated kinase (Sgk), nuclear
      factor for the kappa chain of B-cells (NFkappaB), seven in absentia homologue 2
      (Siah2) and FBJ osteosarcoma related oncogene (Fos) showed a 2.5-200-fold
      induction by PACAP between 15 min and 3 h, and mRNA levels returned either to
      baseline or near baseline after 6 h. This work provides new information
      concerning genes whose transient regulation early after PACAP exposure may
      contribute to the expression of the differentiated transcriptome in PC12 cells,
      and should help to elucidate the molecular mechanisms involved in the control of
      nerve cell survival and differentiation.

PMID- 16787410
TI  - Do axonal defects in tau and amyloid precursor protein transgenic animals model
      axonopathy in Alzheimer's disease?
AB  - The subcellular localization of organelles, mRNAs and proteins is particularly
      challenging in neurons. Owing to their extended morphology, with axons in humans
      exceeding a meter in length, in addition to which they are not renewed but
      persist for the entire lifespan, it is no surprise that neurons are highly
      vulnerable to any perturbation of their sophisticated transport machinery. There
      is emerging evidence that impaired transport is not only causative for a range of
      motor disorders, but possibly also for Alzheimer's disease (AD) and related
      neurodegenerative disorders. Support for this hypothesis comes from transgenic
      animal models. Overexpression of human tau and amyloid precursor protein (APP) in
      mice and flies models the key hallmark histopathological characteristics of AD,
      such as somatodendritic accumulation of phosphorylated forms of tau and beta
      amyloid (Abeta) peptide-containing amyloid plaques, as well as axonopathy. The
      latter has also been demonstrated in mutant mice with altered levels of Alzheimer
      associated genes, such as presenilin (PS). In Abeta-producing APP transgenic
      mice, axonopathy was observed before the onset of plaque formation and tau
      hyperphosphorylation. In human AD brain, an axonopathy was revealed for early but
      not late Braak stages. The overall picture is that key players in AD, such as
      tau, APP and PS, perturb axonal transport early on in AD, causing impaired
      synaptic plasticity and reducing survival rates. It will be challenging to
      determine the molecular mechanisms of these different axonopathies, as this might
      assist in the development of new therapeutic strategies.

PMID- 16787411
TI  - Neurotoxic mechanisms of 2,9-dimethyl-beta-carbolinium ion in primary
      dopaminergic culture.
AB  - beta-Carbolines are potential endogenous and exogenous neurotoxicants that may
      contribute to the pathogenesis of Parkinson's disease. The 2,9-dimethyl-beta
      carbolinium ion (either 2,9-dimethyl-beta-norharmanium or 2,9-Me(2)NH(+)) was
      found to be neurotoxic in primary mesencephalic cultures and to be a potent
      inhibitor of mitochondrial complex I. However, the precise mechanisms of cell
      death remained obscure. Here, we investigated the mechanism of cell death in
      primary dopaminergic cultures of the mouse mesencephalon mediated by 2,9
      Me(2)NH(+). The beta-carboline caused preferential death of dopaminergic
      neurones, which could not be attributed to cellular uptake via the dopamine
      transporter. Transient incubation with 2,9-Me(2)NH(+) for 48 h caused a
      progressive deterioration in the morphology of dopaminergic neurones during a 5
      day recovery period and persistent damage to the overall culture. An increase in
      free radical production and caspase-3 activity, as well as a decrease of
      respiratory activity, mitochondrial membrane potential and ATP content,
      contributed to toxicity and pointed to an apoptotic mode of cell death, although
      a significant quantity of cells dying via necrosis were present simultaneously.
      These data underline the preferential susceptibility of dopaminergic neurones to
      2,9-Me(2)NH(+) as a potent, oxidative stress generating neurotoxin.

PMID- 16787412
TI  - The LGI1/epitempin gene encodes two protein isoforms differentially expressed in
      human brain.
AB  - The leucine-rich, glioma inactivated 1 (LGI1)/Epitempin gene has been linked to
      two phenotypes as different as gliomagenesis and autosomal dominant lateral
      temporal epilepsy. Its function and the biochemical features of the encoded
      protein are unknown. We characterized the LGI1/Epitempin protein product by
      western blot analysis of mouse and human brain tissues. Two proteins of about 60
      and 65 kDa were detected by an anti-LGI1 antibody within the expected molecular
      mass range. The two proteins appeared to reside in different subcellular
      compartments, as they were fractionated by differential centrifugation. The
      specificity of both polypeptides was validated by cell transfection assay and
      mass spectrometry analysis. Immunoblot analysis of protein distribution in
      various zones of the human brain revealed variable amounts of both proteins.
      Notably, these proteins were more abundant in the temporal neocortex than in the
      hippocampus, the difference in abundance of the 65-kDa product being particularly
      pronounced. These results suggest that the two protein isoforms encoded by
      LGI1/Epitempin are differentially expressed in the human brain, and that higher
      expression levels of these proteins in the lateral temporal cortex may underlie
      the susceptibility of this brain region to the epileptogenic effects of
      LGI1/Epitempin mutations.

PMID- 16787413
TI  - Defective axonal transport of neurofilament proteins in neurons overexpressing
      peripherin.
AB  - Peripherin is a type III neuronal intermediate filament detected in motor neuron
      inclusions of amyotrophic lateral sclerosis (ALS) patients. We previously
      reported that overexpression of peripherin provokes late-onset motor neuron
      dysfunction in transgenic mice. Here, we show that peripherin overexpression
      slows down axonal transport of neurofilament (NF) proteins, and that the
      transport defect precedes by several months the appearance of axonal spheroids in
      adult mice. Defective NF transport by peripherin up-regulation was further
      confirmed with dorsal root ganglia (DRG) neurons cultured from peripherin
      transgenic embryos. Immunofluorescence microscopy and western blotting revealed
      that excess peripherin provokes reduction in levels of hyperphosphorylated NF-H
      species in DRG neurites. Similarly the transport of a green fluorescent protein
      (GFP)-tagged NF-M, delivered by means of a lentiviral construct, was impaired in
      DRG neurites overexpressing peripherin. These results demonstrate that peripherin
      overexpression can cause defective transport of type IV NF proteins, a phenomenon
      that may account for the progressive formation of ALS-like spheroids in axons.

PMID- 16787414
TI  - Troglitazone, a peroxisome proliferator-activated receptor-gamma agonist,
      decreases tau phosphorylation in CHOtau4R cells.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the
      nuclear receptor superfamily, is activated by several compounds including the
      thiazolidinediones. In addition to being a target for diabetes, PPARgamma
      activation state has recently been shown to modulate beta-amyloid peptide (Abeta)
      production in cellular models relevant to Alzheimer's disease. Here, we report
      the effect of troglitazone, a thiazolidinedione, in cells expressing 4-repeat
      tau. A 24 h treatment with troglitazone significantly reduced phosphorylation of
      tau at Ser202 and Ser396/404, residues of early and later stages of
      neurofibrillary tangle accumulation in Alzheimer's disease and other
      neurodegenerative disorders. Under the same experimental conditions the level of
      tau did not change. In our cellular model, troglitazone appeared to enhance 3'
      phosphoinositide-dependent protein kinase 1 (PDK1) nuclear translocation,
      resulting in a decrease in cytosolic phosphorylated 70 kDa ribosomal protein
      kinase (p70S6) and phosphorylated mammalian target of rapamycin (mTor).
      Furthermore, PPARgamma transcriptional activity did not appear to be responsible
      for decreased phosphorylation of tau. Thus, we believe that the thiazolidinedione
      regulates tau phosphorylation through a PPARgamma-dependent/independent mechanism
      involving an Akt/glycogen synthase kinase-3(GSK-3beta)-independent signalling
      cascade: PDK1/p70S6K/mTor.

PMID- 16787415
TI  - Glutamate-induced octamer DNA binding and transcriptional control in cultured
      radial glia cells.
AB  - Glutamate, the main excitatory neurotransmitter in the vertebrate brain, is
      critically involved in gene expression regulation in neurons and in glia cells.
      Neuron-glia interactions provide the framework for synaptic plasticity. Retinal
      and cerebellar radial glia cells surround glutamatergic excitatory synapses and
      sense synaptic activity through glutamate receptors expressed in their membranes.
      Several glutamate-dependent membrane to nuclei signaling cascades have been
      described in these cells. Octamer DNA binding factors, namely Oct-1 and Oct-2
      recognize similar DNA sequences on regulatory regions, but their final
      transcriptional effect depends on several factors. By these means, different
      responses can be achieved in different cell types. Here, we describe a comparison
      between the glutamate-induced DNA binding of octamer factors and their functional
      activities in two important types of radial glia, retinal Muller and cerebellar
      Bergmann glial cells. While Oct-1 is expressed in both cell types and in both
      glutamate treatments results in an increase in Oct-1 DNA binding, this complex is
      capable of transactivating a reporter gene only in Muller glia cells. In
      contrast, Oct-2 expression is restricted to Bergmann glia cells in which
      glutamate treatment results in an augmentation of Oct-2 DNA binding complexes and
      the repression of kainate binding protein gene transcription. Our present
      findings demonstrate a differential role for Oct-1 and Oct-2 transcription
      factors in glial glutamate signaling, and further strengthen the notion of an
      important role for glial cells in glutamatergic transactions in the central
      nervous system.

PMID- 16787416
TI  - Cyclooxygenase-1 and -2 enzymes differentially regulate the brain upstream NF
      kappa B pathway and downstream enzymes involved in prostaglandin biosynthesis.
AB  - We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain
      upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to
      prostaglandin E2 (PGE2), as well as enzyme activity, protein and mRNA levels of
      the reciprocal isozyme, COX-1. To gain a better insight into the specific roles
      of COX isoforms and characterize the interactions between upstream and downstream
      enzymes in brain AA cascade, we examined the expression and activity of COX-2 and
      phospholipase A2 enzymes (cPLA2 and sPLA2), as well as the expression of terminal
      prostaglandin E synthases (cPGES, mPGES-1, and - 2) in wild type and COX-1(-/-)
      mice. We found that brain PGE2 concentration was significantly increased, whereas
      thromboxane B2 (TXB2) concentration was decreased in COX-1(-/-) mice. There was a
      compensatory up-regulation of COX-2, accompanied by the activation of the NF
      kappaB pathway, and also an increase in the upstream cPLA2 and sPLA2 enzymes. The
      mechanism of NF-kappaB activation in the COX-1(-/-) mice involved the up
      regulation of protein expression of the p50 and p65 subunits of NF-kappaB, as
      well as the increased protein levels of phosphorylated IkappaBalpha and of
      phosphorylated IKKalpha/beta. Overall, our data suggest that COX-1 and COX-2 play
      a distinct role in brain PG biosynthesis, with basal PGE2 production being
      metabolically coupled with COX-2 and TXB2 production being preferentially linked
      to COX-1. Additionally, COX-1 deficiency can affect the expression of reciprocal
      and coupled enzymes, COX-2, Ca2+ -dependent PLA2, and terminal mPGES-2, to
      overcome defects in brain AA cascade.

PMID- 16787417
TI  - GRK1 and GRK7: unique cellular distribution and widely different activities of
      opsin phosphorylation in the zebrafish rods and cones.
AB  - Retinal cone cells exhibit distinctive photoresponse with a more restrained
      sensitivity to light and a more rapid shutoff kinetics than those of rods. To
      understand the molecular basis for these characteristics of cone responses, we
      focused on the opsin deactivation process initiated by G protein-coupled receptor
      kinase (GRK) 1 and GRK7 in the zebrafish, an animal model suitable for studies on
      retinal physiology and biochemistry. Screening of the ocular cDNAs identified two
      homologs for each of GRK1 (1A and 1B) and GRK7 (7-1 and 7-2), and they were
      classified into three GRK subfamilies, 1 A, 1B and 7 by phylogenetic analysis. In
      situ hybridization and immunohistochemical studies localized both GRK1B and GRK7
      1 in the cone outer segments and GRK1A in the rod outer segments. The opsin/GRKs
      molar ratio was estimated to be 569 in the rod and 153 in the cone. The
      recombinant GRKs phosphorylated light-activated rhodopsin, and the Vmax value of
      the major cone subtype, GRK7-1, was 32-fold higher than that of the rod kinase,
      GRK1A. The reinforced activity of the cone kinase should provide a strengthened
      shutoff mechanism of the light-signaling in the cone and contribute to the
      characteristics of the cone responses by reducing signal amplification
      efficiency.

PMID- 16787418
TI  - Enhanced cortical and accumbal molecular reactivity associated with conditioned
      heroin, but not sucrose-seeking behaviour.
AB  - Re-exposure to drug-related cues elicits drug-seeking behaviour and relapse in
      both humans and laboratory animals even after months of abstinence. Identifying
      neural and molecular substrates underlying conditioned heroin-seeking behaviour
      will be helpful in understanding mechanisms behind opiate relapse. In humans and
      animals, brain areas activated by natural reward-related stimuli (e.g. food, sex)
      do not show a complete overlap with those activated by stimuli associated with
      drugs of abuse, suggesting the involvement of different circuitry. To that end,
      we investigated neural reactivity by measuring immediate early gene (IEG)
      expression patterns in mesocorticolimbic system target areas following cue
      induced reinstatement of heroin seeking and compared those IEG expression
      patterns to what was measured during natural reward (sucrose)-seeking behaviour.
      Animals were trained to administer heroin associated with a compound audio-visual
      cue. Re-exposure to the cue after 3 weeks of withdrawal reinstated heroin-seeking
      behaviour, which resulted in IEG expression of ania-3, MKP-1, c-fos and Nr4a3 in
      the medial prefrontal cortex (mPFC), and of ania-3 in the orbital frontal cortex
      (OFC) and nucleus accumbens core (NAC). The expression patterns for heroin
      seeking behaviours did not generalize to sucrose-seeking behaviours, indicating
      that the two behaviours involve different connectivity pathways of neuronal
      signalling.

PMID- 16787419
TI  - Chaperone protein 14-3-3 and protein kinase A increase the relative abundance of
      low agonist sensitivity human alpha 4 beta 2 nicotinic acetylcholine receptors in
      Xenopus oocytes.
AB  - Alpha4 and beta2 nicotinic acetylcholine (nACh) receptor subunits expressed
      heterologously in Xenopus oocytes assemble into a mixture of receptors with high
      and low agonist sensitivity whose relative abundance is influenced by the
      heteropentamer subunit ratio. We have found that inhibition of protein kinase A
      by KT5720 decreased maximal [3H]cytisine binding and acetylcholine (ACh)-induced
      current responses, and increased the relative proportion of alpha4beta2 receptors
      with high agonist sensitivity. Mutation of serine 467, a putative protein kinase
      A substrate in a chaperone protein binding motif within the large cytoplasmic
      domain of the alpha4 subunit, to alanine or asparate decreased or increased,
      respectively, maximal [3H]cytisine binding and ACh response amplitude. Expression
      of alpha4S467A mutant subunits decreased steady levels of alpha4 and the relative
      proportion of alpha4beta2 receptors with low agonist sensitivity, whilst
      expression of alpha4S467D increased steady levels of alpha4 and alpha4beta2
      receptors with low agonist sensitivity. Difopein, an inhibitor of chaperone 14-3
      3 proteins, decreased [3H]cytisine binding and ACh responses and increased the
      proportion of alpha4beta2 with high sensitivity to activation by ACh. Thus, post
      translational modification affecting steady-state levels of alpha4 subunits
      provides a possible means for physiologically relevant, chaperone-mediated
      variation in the relative proportion of high and low agonist sensitivity
      alpha4beta2 nACh receptors.

PMID- 16787420
TI  - The radical scavenger CR-6 protects SH-SY5Y neuroblastoma cells from oxidative
      stress-induced apoptosis: effect on survival pathways.
AB  - Reactive oxygen species (ROS) and oxidative stress have long been linked to cell
      death of neurons in many neurodegenerative conditions. However, the exact
      molecular mechanisms triggered by oxidative stress in neurodegeneration are at
      present unclear. In the current work we have used the human neuroblastoma SH-SY5Y
      cell line as a model for studying the molecular events occurring after inducing
      apoptosis with H2O2. We show that treatment of SH-SY5Y cells with H2O2 up
      regulates survival pathways during early stages of apoptosis. Subsequently, the
      decline of anti-apoptotic protein levels leads to the activation of the calcium
      dependent proteases calpains and the cysteine proteases caspases. Additionally,
      we demonstrate that CR-6 (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)
      benzopyran) acts as a scavenger of ROS and prevents apoptosis by enhancing and
      prolonging up-regulation of survival pathways. Furthermore, we show that pre
      treatment of SH-SY5Y cells with a cocktail containing CR-6, the pan-caspase
      inhibitor zVAD-fmk (zVal-Ala-Asp-fluoro-methylketone) and the calpain inhibitor
      SJA6017 confers almost total protection against apoptosis. In summary, the
      present work characterizes the molecular mechanisms involved in oxidative stress
      induced apoptosis in SH-SY5Y cells. Our findings highlight the relevance of CR-6,
      alone or in combination with other drugs, as potential therapeutic strategy for
      the treatment of neurodegenerative diseases.

PMID- 16787421
TI  - The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter
      homeostasis and ammonia transfer.
AB  - Neurons are metabolically handicapped in the sense that they are not able to
      perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric
      acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA
      glutamine cycle describes the release of neurotransmitter glutamate or GABA from
      neurons and subsequent uptake into astrocytes. In return, astrocytes release
      glutamine to be taken up into neurons for use as neurotransmitter precursor. In
      this review, the basic properties of the glutamate/GABA-glutamine cycle will be
      discussed, including aspects of transport and metabolism. Discussions of
      stoichiometry, the relative role of glutamate vs. GABA and pathological
      conditions affecting the glutamate/GABA-glutamine cycling are presented.
      Furthermore, a section is devoted to the accompanying ammonia homeostasis of the
      glutamate/GABA-glutamine cycle, examining the possible means of intercellular
      transfer of ammonia produced in neurons (when glutamine is deamidated to
      glutamate) and utilized in astrocytes (for amidation of glutamate) when the
      glutamate/GABA-glutamine cycle is operating. A main objective of this review is
      to endorse the view that the glutamate/GABA-glutamine cycle must be seen as a bi
      directional transfer of not only carbon units but also nitrogen units.

PMID- 16787422
TI  - Prion protein reduces both oxidative and non-oxidative copper toxicity.
AB  - The prion protein is a membrane tethered glycoprotein that binds copper.
      Conversion to an abnormal isoform is associated with neurodegenerative diseases
      known as prion diseases. Expression of the prion protein has been suggested to
      prevent cell death caused by oxidative stress. Using cell based models we
      investigated the potential of the prion protein to protect against copper
      toxicity. Although prion protein expression effectively protected neurones from
      copper toxicity, this protection was not necessarily associated with reduction in
      oxidative damage. We also showed that glycine and the prion protein could both
      protect neuronal cells from oxidative stress. Only the prion protein could
      protect these cells from the toxicity of copper. In contrast glycine increased
      copper toxicity without any apparent oxidative stress or lipid peroxidation.
      Mutational analysis showed that protection by the prion protein was dependent
      upon the copper binding octameric repeat region. Our findings demonstrate that
      copper toxicity can be independent of measured oxidative stress and that prion
      protein expression primarily protects against copper toxicity independently of
      the mechanism of cell death.

PMID- 16787423
TI  - The regulation of acetylcholinesterase by cis-elements within intron I in
      cultured contracting myotubes.
AB  - The onset of spontaneous contraction in rat primary muscle cultures coincides
      with an increase in acetylcholinesterase (AChE) activity. In order to establish
      whether contractile activity modulates the rate of AChE transcript synthesis, and
      what elements of the gene are determinant, we examined the promoter and intron I
      in contracting muscle cultures. Ache genomic fragments attached to a luciferase
      reporter were transfected into muscle cultures that were either electrically
      stimulated or paralyzed with tetrodotoxin to enhance or inhibit contractions,
      respectively. Cultures transfected with intron I-containing constructs showed a 2
      fold increase in luciferase activity following electrical stimulation, compared
      to tetrodotoxin treatment, suggesting that this region contains elements
      responding to contractile activity. Deleting a 780 bp distal region within intron
      I, containing an N-box element at +890 bp, or introducing a 2-bp mutation within
      its core sequence, eliminated the contraction-induced response. In contrast,
      mutating an N-box element at +822 bp had no effect on the response. Furthermore,
      co-transfecting a dominant negative GA-binding protein (GABP), a transcription
      factor known to selectively bind N-box elements, reduced the stimulation-mediated
      increase. Our results suggest that the N-box within intron I at +890 bp is a
      regulatory element important in the transcriptional response of Ache to
      contractile activity in muscle.

PMID- 16787424
TI  - Phosphorylation of rat brain mitochondrial voltage-dependent anion as a potential
      tool to control leakage of cytochrome c.
AB  - Apoptosis is a controlled form of cell death that participates in development,
      elimination of damaged cells and maintenance of cell homeostasis. Also, it plays
      a role in neurodegenerative disorders like Alzheimer's disease. Recently,
      mitochondria have emerged as being pivotal in controlling apoptosis. They house a
      number of apoptogenic molecules, such as cytochrome c, which are released into
      the cytoplasm at the onset of apoptosis. When rat brain mitochondrial voltage
      dependent anion channel (VDAC), an outer mitochondrial membrane protein,
      interacts with Bcl-2 family proteins Bax and tBid, its pore size increases,
      leading to the release of cytochrome c and other apoptogenic molecules into the
      cytosol and causing cell death. Regulation of this tBid- and Bax-induced increase
      in pore size of VDAC is a significant step to control cell death induced by
      cytochrome c. In this work, we have shown, through bilayer electrophysiological
      experiments, that the increase in VDAC conductance as a result of its interaction
      with Bax and tBid is reduced because of the action of cyclic AMP-dependent
      protein kinase A (PKA) in the presence of ATP. This indicates that the increase
      in the pore size of VDAC after its interaction with Bax and tBid is controlled
      via phosphorylation of this channel by PKA. This, we believe, could be a
      mechanism of controlling cytochrome c-mediated cell death in living cells.

PMID- 16787425
TI  - Loving, hating, vacillating: Agreeableness, implicit self-esteem, and neurotic
      conflict.
AB  - An implicit preference for the self over others may be beneficial when pursuing
      one's own desires but costly when adjusting the self to the desires of others. On
      the basis of this reasoning, the authors hypothesized that Agreeableness and
      implicit self-esteem would interact in predicting measures of neurotic distress.
      Three studies and one meta-analysis, involving 235 undergraduate participants,
      confirmed that high levels of implicit self-esteem were beneficial (i.e., less
      neurotic distress) within the context of low levels of Agreeableness but costly
      (i.e., more neurotic distress) within the context of high levels of
      Agreeableness. Because findings were robust across various measures of
      Agreeableness, implicit self-esteem, and neurotic distress, the interpersonal
      principles examined here appear to have broad relevance for understanding this
      particular form of intrapsychic conflict and its manifestation in neurotic
      distress. Results therefore support Horney's (1945) theory concerning the
      consequences of intrapsychic conflicts related to interpersonal motivation and
      cognition.

PMID- 16787426
TI  - Individual differences in approach and avoidance movements: how the avoidance
      motive influences response force.
AB  - The present research is based on the assumption that people differ in their
      responsiveness to incentives and threats. In two experiments we examined whether
      the trait corresponding to the responsiveness to threats (avoidance motive) and
      the trait corresponding to the responsiveness to incentives (approach motive)
      influence voluntary motor behavior toward or away from stimuli. In Experiment 1,
      stimuli consisted of positive and negative words within a lexical decision task.
      Participants moved their arms backward in order to withdraw from the stimuli or
      forward in order to approach them. In Experiment 2, participants responded with
      forward or backward arm movements to neutral sounds coming from behind or in
      front of them. The main dependent variable was the strength of the approach and
      avoidance movements. In both experiments this variable was related to
      participants' avoidance-motive disposition but not to their approach-motive
      disposition. Avoidance-motivated individuals generally showed more forceful
      avoidance movements than approach movements. There was no effect of stimulus
      valence on the strength of the movements in Experiment 1. Furthermore, the
      results of Experiment 2 suggest that it is not the physical direction (forward or
      backward) but rather the movement's effect of distance reduction (approach) or
      distance increase (avoidance) in regard to the stimulus that defines a movement
      as an approach or an avoidance movement.

PMID- 16787427
TI  - Trait and social processes in the link between social support and affect: an
      experimental, laboratory investigation.
AB  - This study investigated the extent to which the link between perceived social
      support and affect reflected support recipients' trait perceived support as well
      as three distinct social processes: the objective supportiveness of providers,
      the unique relationships among recipients and providers that were stable over
      occasions, as well as the unique relationships that varied across occasions. Ten
      recipients interacted with each of the same four providers on five separate
      occasions, for a total of 200 interactions. Recipients and independent observers
      rated recipient affect and provider support. Greater perceived support was
      related to greater positive affect for recipients' trait perceived support, as
      well as for relationships that were stable over occasions and relationships that
      varied across occasions. No social support effects were found for negative
      affect. Perceived similarity was a consistent predictor of recipients' support
      perceptions. Implications for social support models and interventions were
      discussed.

PMID- 16787428
TI  - Self-liking and self-competence separate self-evaluation from self-deception:
      associations with personality, ability, and achievement.
AB  - The similarities between measures of self-evaluation and self-deception are
      reviewed, and a method for discriminating between them is proposed, using
      personality profiles and relations to ability and achievement. Across two
      samples, the Rosenberg Self-Esteem Scale (RSES) and Tafarodi's measures of self
      evaluation were used to demonstrate that the RSES and Self-Liking are more
      similar to Self-Deceptive Enhancement than is self-competence. Further, Self
      Competence is uniquely associated with cognitive ability and both academic and
      creative achievement. It is concluded that, along with self-liking, self
      competence is a useful form of self-evaluation that should be measured and taken
      into account in research that has traditionally focused on self-esteem.

PMID- 16787429
TI  - Narrative identity processing of difficult life experiences: pathways of
      personality development and positive self-transformation in adulthood.
AB  - Difficult life experiences in adulthood constitute a challenge to the narrative
      construction of identity. Individual differences in how adults respond to this
      challenge were conceptualized in terms of two dimensions of narrative identity
      processing: exploratory narrative processing and coherent positive resolution.
      These dimensions, coded from narratives of difficult experiences reported by the
      women of the Mills Longitudinal Study (Helson, 1967) at age 52, were expected to
      be related to personality traits and to have implications for pathways of
      personality development and physical health. First, the exploratory narrative
      processing of difficult experiences mediated the relationship between the trait
      of coping openness in young adulthood (age 21) and the outcome of maturity in
      late midlife (age 61). Second, coherent positive resolution predicted increasing
      ego-resiliency between young adulthood and midlife (age 52), and this pattern of
      increasing ego-resiliency, in turn, mediated the relationship between coherent
      positive resolution and life satisfaction in late midlife. Finally, the
      integration of exploratory narrative processing and coherent positive resolution
      predicted positive self-transformation within narratives of difficult
      experiences. In turn, positive self-transformation uniquely predicted optimal
      development (composite of maturity and life satisfaction) and physical health.

PMID- 16787430
TI  - Socioeconomic status in childhood and adulthood: associations with dispositional
      optimism and pessimism over a 21-year follow-up.
AB  - We examined whether dispositional optimism and pessimism (overall LOT-R and
      optimism and pessimism component scores) of 694 adults aged 24 and 27 were
      associated with socioeconomic status (SES) measured concurrently and in childhood
      at ages 3 and 6. SES measures included education, occupational status and
      unemployment, and income. Concurrent adulthood SES was associated with the
      overall LOT-R and optimism and the pessimism component scores. Childhood family
      SES predicted overall LOT-R and pessimism component scores, even after
      controlling statistically for the adulthood SES. Social mobility between SES of
      family of origin and current SES also influenced the scores. The current findings
      suggest that the foundation of dispositional optimism and pessimism is related to
      early SES of the family.

PMID- 16787431
TI  - Why extraverts are happier than introverts: the role of mood regulation.
AB  - Three studies tested the hypotheses that extraverts demonstrate better mood
      maintenance abilities than introverts and that these mood regulation abilities
      can account for the higher habitual happiness of extraverts. Using self- and peer
      rated trait measures, Study 1 provided multimethod evidence that mood
      maintenance, but not mood repair, accounted for the link between extraversion and
      pleasant-unpleasant trait mood. Study 2 replicated this finding in a different
      sample of self-reports. Using a within-subjects design, Study 3 demonstrated that
      when confronted with an affectively ambivalent situation, extraverts maintained a
      more positive affect balance than introverts. Habitual mood maintenance mediated
      the effect of extraversion on pleasant-unpleasant affect change. Taken together,
      the findings support a self-regulation explanation of the extraversion-pleasant
      affect link.

PMID- 16787432
TI  - Adult attachment and the perception of emotional expressions: probing the
      hyperactivating strategies underlying anxious attachment.
AB  - According to adult attachment theory, individual differences in attachment
      related anxiety reflect variation in individuals' vigilance to cues relevant to
      appraising and monitoring the availability and responsiveness of significant
      others. To investigate this assumption, the authors adopted a morph movie
      paradigm in which participants were shown movies of faces in which an emotional
      facial expression changed gradually to a neutral one (Study 1) or a neutral
      expression changed to an emotional one (Studies 2-4). Participants were asked to
      judge the point at which the emotional expression had disappeared or emerged,
      respectively. Individuals who were highly anxious with respect to attachment were
      more likely to perceive the offset (Study 1) as well as the onset (Studies 2 and
      3) of the facial expressions of emotion earlier than other people. Moreover, this
      heightened state of vigilance may have led to poorer accuracy in judging facial
      expressions of emotion (Study 3), an effect that was reversed when anxious
      individuals were required to watch the movies for the same length of time as less
      anxious participants (Study 4). The results indicate that variation in attachment
      anxiety reflects, in part, differences in vigilance to cues of social and
      emotional significance.

PMID- 16787433
TI  - Bridging the idiographic-nomothetic divide: a follow-up study.
AB  - In a replication and extension of Grice (2004), participants in the current study
      rated themselves and other known individuals on scales constructed from their own
      personal constructs and on marker items for the Big Five model personality
      traits. Confirmatory components analyses revealed excellent fit for the Big Five
      Model when applied to aggregate trait ratings but highly variable fit when
      applied to participants' individual ratings. Comparisons of the personal
      construct and trait ratings indicated an approximate average overlap of only 51%,
      and additional analyses revealed several factors that contributed to the
      uniqueness of the personal constructs. These findings were discussed in the
      context of the idiographic-nomothetic distinction drawn in personality
      psychology.

PMID- 16787434
TI  - Does ideology transcend culture? A preliminary examination in Romania.
AB  - This article represents a preliminary attempt to develop a culturally universal
      structural model of ideology. In Study 1, an indigenous model of Romanian
      ideology was developed. The structural model was created by converting 245
      dictionary definitions of Romanian ideological concepts into questionnaire items.
      Using a sample of 420 Romanians, the most replicable structure indicated four
      broad dimensions that appeared to roughly correspond to the four factors in
      Saucier's (2000) American model of ideology. Study 2 replicated the structural
      model and compared it with existing ideological measures. Authoritarianism and
      traditional religiosity were a key component of the largest factor. Communism and
      some aspects of social dominance orientation were key components of the second
      largest factor. The findings may represent the beginnings of a culturally
      universal structure model of ideology.

PMID- 16787435
TI  - Ultrastructure of long-range transport carriers moving from the trans Golgi
      network to peripheral endosomes.
AB  - The delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from
      the trans-Golgi network (TGN) to the endosomal system is mediated by selective
      incorporation of the receptor-hydrolase complexes into vesicular transport
      carriers (TCs) that are coated with clathrin and the adaptor proteins, GGA and AP
      1. Previous electron microscopy (EM) and biochemical studies have shown that
      these TCs consist of spherical coated vesicles with a diameter of 60-100 nm. The
      use of fluorescent live cell imaging, however, has revealed that at least some of
      this transport relies on a subset of apparently larger and highly pleiomorphic
      carriers that detach from the TGN and translocate toward the peripheral cytoplasm
      until they meet with distally located endosomes. The ultrastructure of such long
      range TCs has remained obscure because of the inability to examine by
      conventional EM the morphological details of rapidly moving organelles. The
      recent development of correlative light-EM has now allowed us to obtain
      ultrastructural 'snapshots' of these TCs immediately after their formation from
      the TGN in live cells. This approach has revealed that such carriers range from
      typical 60- to 100-nm clathrin-coated vesicles to larger, convoluted tubular
      vesicular structures displaying several coated buds. We propose that this subset
      of TCs serve as vehicles for long-range distribution of biosynthetic or recycling
      cargo from the TGN to the peripheral endosomes.

PMID- 16787436
TI  - The efficiency of different chemoradiotherapy regimens in patients with
      paediatric nasopharynx cancer: review of 46 cases.
AB  - The purpose of this study was to evaluate the role of combined modality treatment
      in patients with paediatric nasopharynx cancer (NPC). Forty-six patients with
      paediatric NPC were retrospectively analysed. Forty-four of 46 patients received
      combined modality treatment. Five-year overall survival and progression-free
      survivals were 70% and 72% for the whole group, and only three of 46 patients had
      loco-regional relapse. Complete remission was obtained in 18 of 45 patients
      (40%), and the overall survival (94% vs. 62% and 19%, p = 0.0009) and disease
      free survivals (93% vs. 70% and 16%, p = 0.0002) were significantly better in
      complete responders when compared with the patients who had partial response or
      stable disease. The 5-year overall survival and disease-free survivals of the
      patients who received neoadjuvant chemotherapy (CT) and radiotherapy (RT)
      followed by CT were superior to the other groups (77% and 80%, respectively). The
      number of total CT cycles (p = 0.0001), nodal stage (p = 0.05) and treatment
      response (p = 0.0009) were significant prognostic factors for overall survival.
      The treatment type (p = 0.02), the number of total CT cycles (p = 0.0006), nodal
      stage (p = 0.05) and treatment response (p = 0.0002) were found as significant
      prognostic factors for disease-free survival. The survival of patients receiving
      six or more CT cycles was also significantly better than that of patients
      receiving less than six cycles (p = 0.0001). In patients with locally advanced
      paediatric NPC, CT should be added to RT to improve outcome. However, a standard
      protocol is yet to be identified, and further studies evaluating the addition of
      interferon or immunotherapy to CT and RT shall be performed.

PMID- 16787437
TI  - Metoclopramide aborts cough-induced headache and ameliorates cough--a pilot
      study.
AB  - Metoclopramide (MTCL) can abort attacks of migraine headache. I report swift
      resolution of cough-induced headache as well as suppression of cough in six male
      patients following parenteral administration of MTCL. A similar unexpected rapid
      antitussive action of MTCL was also observed in 12 of 14 other patients (13 male
      and 1 female) with severe paroxysmal cough without headache. Use of MTCL
      primarily for analgesia is reviewed, and the pharmacological basis for its
      antinociceptive action is proposed. As a nonopiate agent with potential to
      stimulate endogenous opiate-mediated mechanisms, MTCL appears to have additional
      valuable roles in clinical practice. This is the first report of an antitussive
      action of MTCL. Further controlled studies are required to confirm the
      therapeutic role of MTCL in cough-induced headache as well as its potential
      antitussive and general analgesic actions.

PMID- 16787438
TI  - The anxieties of medical students related to clinical training.
AB  - High levels of anxiety and stress during medical education may have negative
      effects on students' learning and may also influence students' performance,
      decision-making and caring capabilities. This study aims to compare the anxieties
      of clerkships of two medical schools that apply two different preclinical
      curricula; one is problem-based and the other is integrated. Dokuz Eylul
      University School of Medicine (DEUSM) has the basic clinical and communication
      skills education by the first year of medical education. However, the students of
      Marmara University School of Medicine (MUSM) had not any preclinical training
      about these issues at the time we performed this study. In order to evaluate the
      perceived anxiety, we used a questionnaire which comprises 39 issues presented as
      4-point Likert-type scales. Eighty-six clerkships from MUSM and 115 clerkships
      from DEUSM participated in the study. According to the students of both of the
      schools, fear of making mistakes that could harm the patients was at the top of
      the list of sources of anxiety. The students of MUSM have additional anxieties
      related to the core clinical skills such as suturing patients, taking blood from
      patients and giving injections. On the other hand, the students of DEUSM have
      anxieties mostly related to difficult issues in communication such as breaking
      bad news. The study has revealed that medical students might have anxiety related
      to the clinical practice in the beginning of their clerkships. It was also shown
      that sources of anxiety may vary among students exposed to different preclinical
      curricula and different educational environment. If basic clinical and
      communication skills courses are integrated in preclinical curriculum, the
      students would meet some clinical task in the early year and would be orientated
      through clinical period.

PMID- 16787439
TI  - Drug intolerance in patients with idiopathic environmental intolerance syndrome.
AB  - The increasing rate of the idiopathic environmental intolerance (IEI) has been
      observed for the last decade. The aim of this report was to analyse the allergic
      component of the disease in particular relation to drug intolerance. Six patients
      with diagnosed IEI showed a positive skin test reaction to several commonly used
      antibiotics, nonsteroidal anti-inflammatory drugs, myorelaxants, verapamil, etc.
      In three cases, the thorough diagnosis of sensitivity to anaesthetic agents
      enabled to perform necessary surgical treatment, in others - facilitated the
      proper treatment of headaches and hypertension. Symptoms related to allergy
      contributed to the deterioration of IEI. Thus, a consultation of IEI patients by
      an allergologist seems to be of a substantial importance.

PMID- 16787440
TI  - Regression of post-transplant Kaposi's sarcoma using sirolimus.
AB  - Kaposi's sarcoma (KS) is a recognised complication following kidney
      transplantation, but the incidence varies according to the geographical area.
      Although it is a rare tumour, its incidence increases dramatically after solid
      organ transplantation. The immunosuppressive medications reactivate human herpes
      virus 8, which has been proposed as the offending agent. The usual treatment of
      KS is to reduce immunosuppression, chemotherapy and radiotherapy. Nevertheless,
      the mortality still remains considerably high and has been reported between 8 and
      14%. Sirolimus (SRL) has properties which may be useful in the management of some
      posttransplant tumours such as KS. We report a renal transplant patient with KS,
      who had multiple relapses after radiotherapy but responded well to the change of
      immunosuppression from cyclosporine to SRL.

PMID- 16787441
TI  - Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell
      lines. A possible strategy for the maintenance of intracellular heme level.
AB  - Heme oxygenase consists of two structurally related isozymes, heme oxygenase-1
      and and heme oxygenase-2, each of which cleaves heme to form biliverdin, iron and
      carbon monoxide. Expression of heme oxygenase-1 is increased or decreased
      depending on cellular microenvironments, whereas little is known about the
      regulation of heme oxygenase-2 expression. Here we show that hypoxia (1% oxygen)
      reduces the expression levels of heme oxygenase-2 mRNA and protein after 48 h of
      incubation in human cell lines, including Jurkat T-lymphocytes, YN-1 and K562
      erythroleukemia, HeLa cervical cancer, and HepG2 hepatoma, as judged by northern
      blot and western blot analyses. In contrast, the expression level of heme
      oxygenase-1 mRNA varies under hypoxia, depending on the cell line; it was
      increased in YN-1 cells, decreased in HeLa and HepG2 cells, and remained
      undetectable in Jurkat and K562 cells. Moreover, heme oxygenase-1 protein was
      decreased in YN-1 cells under the conditions used, despite the induction of heme
      oxygenase-1 mRNA under hypoxia. The heme oxygenase activity was significantly
      decreased in YN-1, K562 and HepG2 cells after 48 h of hypoxia. To explore the
      mechanism for the hypoxia-mediated reduction of heme oxygenase-2 expression, we
      showed that hypoxia shortened the half-life of heme oxygenase-2 mRNA (from 12 h
      to 6 h) in YN-1 cells, without affecting the half-life of heme oxygenase-1 mRNA
      (9.5 h). Importantly, the heme contents were increased in YN-1, HepG2 and HeLa
      cells after 48 h of incubation under hypoxia. Thus, the reduced expression of
      heme oxygenase-2 may represent an important adaptation to hypoxia in certain cell
      types, which may contribute to the maintenance of the intracellular heme level.

PMID- 16787443
TI  - A prospective study on knee proprioception after meniscal allograft
      transplantation.
AB  - The meniscus plays an important role in the proprioceptive ability of the knee
      joint. The aim of this prospective study was to assess the short-term influence
      of a meniscus replacement on the proprioception of the knee. Fourteen patients
      who had undergone a fresh meniscal allograft transplantation between May 2001 and
      June 2003 were tested pre-operatively and 6 months post-operatively. Disability
      regarding pain, stiffness and functionality of the affected knee during daily
      activities was measured by the Western Ontario and McMaster Universities
      Arthritis (WOMAC) scale. The knee joint position sense was assessed using the
      Biodex System 3 isokinetic dynamometer. The results of the WOMAC scale showed no
      significant differences concerning pain, stiffness or knee function between the
      pre- and post-operative condition of the knee. Assessment of the knee joint
      position sense at a reference point of 70 degrees of knee flexion revealed a
      significant improvement of the proprioception of the operated knee at 6 months
      after surgery compared with the pre-operative condition. The results of this
      study suggest that although no significant improvement of pain and functionality
      of the operated knee occurred at this short-term follow-up period, a meniscal
      allograft transplantation seems to have a significant positive effect on the
      joint position sense of the previously meniscectomised knee.

PMID- 16787442
TI  - The effect of strenuous aerobic exercise on skeletal muscle myofibrillar
      proteolysis in humans.
AB  - Relatively little is known about the dynamics of the skeletal muscle protein pool
      following aerobic exercise. Myofibrillar protein synthesis has recently been
      shown to be substantially elevated for 3 days after a strenuous 60 min bout of
      one-legged aerobic exercise, and this increase was surprisingly equal to or
      greater than what has been shown numerous times following resistance exercise
      over the same time course. Because net protein accretion is the sum of protein
      synthesis and degradation, we sought to directly measure skeletal muscle
      myofibrillar proteolysis in five healthy young males in response to an identical
      strenuous 60 min aerobic exercise bout and at the same time points (rest, 6, and
      24 h post-exercise and 48 and 72 h post-exercise in a subset of subjects). We
      measured skeletal muscle myofibrillar proteolysis by monitoring the release of
      the natural tracer 3-methylhistidine (3MH) from the vastus lateralis muscle into
      the interstitial space via microdialysis. Skeletal muscle interstitial 3MH
      concentration was no different (P>0.05) from rest (5.16+/-0.38 nmol/mL) after 6
      (5.37+/-0.55 nmol/mL), 24 (5.40+/-0.26 nmol/mL), 48 (5.50+/-0.74 nmol/mL), or 72
      h (4.73+/-0.28 nmol/mL). These results suggest that proteolysis of the
      myofibrillar fraction of skeletal muscle is relatively refractory to an intense
      aerobic exercise stimulus for up to 3 days, despite the large increase in
      synthesis of this muscle fraction following the same exercise stimulus. The
      apparent net myofibrillar protein accretion in the hours and days after exercise
      may occur in order to offset the large elevation in mixed muscle proteolysis that
      has been shown during similar bouts of intense one-legged aerobic exercise.

PMID- 16787444
TI  - Total proximal tendon avulsion of the rectus femoris muscle.
AB  - Total proximal avulsions of the quadriceps femoris muscle group are rare
      injuries. Between the years 2001 and 2004 five patients with a total proximal
      avulsion of the tendon of the rectus femoris muscle were treated surgically in
      Mehilainen Hospital in Turku, Finland. The median age of the patients was 21
      years (range, 19-27) and the patients were all men. There were four soccer
      players and one hurdler. In all cases an avulsion of the proximal tendon of the
      rectus femoris muscle was confirmed by MRI. All of the patients were operated on
      and the delay from the injury to surgery ranged from 18 to 102 days. The result
      of the surgical treatment was rated good in all cases. All of the patients were
      able to return to their pre-injury level of activity 5-10 months after surgery.
      The median follow-up time was 20 months (range, 9-38). Surgical treatment of a
      total proximal avulsion of the tendon of the rectus femoris muscle seems to
      result in return to the pre-injury activity level in most cases.

PMID- 16787445
TI  - Effect of prolonged exercise on arterial oxygen saturation in athletes
      susceptible to exercise-induced hypoxemia.
AB  - This study examined the effect of prolonged endurance exercise on the development
      of exercise-induced hypoxemia (EIH) in athletes who had previously displayed EIH
      during an incremental maximal exercise test. Five male and three female endurance
      trained athletes participated. Susceptibility to EIH was confirmed through a
      maximal incremental exercise test and defined as a reduction in the saturation of
      arterial oxygen (SpO(2)) of >/=4% from rest. Sixty minutes of running was
      conducted, on a separate day, at an oxygen consumption corresponding to 95% of
      ventilatory threshold. Immediately following the 60 min exercise bout, athletes
      commenced a time trial to exhaustion at 95% maximal oxygen consumption
      (VO(2max)). The reduction in SpO(2) was significantly greater during the maximal
      incremental test, than during the 60 min, or time trial to exhaustion (-8.8+/
      1.4%, -3.3+/-1.1%, and -4.1+/-2.3%, P<0.05, respectively). The degree of
      desaturation during the 60 min was significantly related to the relative
      intensity of exercise at 95% ventilatory threshold (adjusted r(2)=0.54, P=0.02).
      In conclusion, athletes who did not exercise at greater than 73% VO(2max) during
      60 min of endurance exercise did not display EIH, despite being previously
      susceptible during an incremental maximal test.

PMID- 16787446
TI  - Decreased shoulder function and pain common in recreational badminton players.
AB  - The aim of this study was to describe the prevalence and consequences of painful
      conditions in the shoulder region in recreational badminton players. A
      questionnaire study was performed on 99 players, of whom 57 were also assessed
      with Constant score. Previous or present pain in the dominant shoulder was
      reported by 52% of the players. Sixteen percent of the players had on-going
      shoulder pain associated with badminton play. A majority of these players
      reported that their training habits were affected by the pain. Total Constant
      score was lower in the painful shoulders. Furthermore, range of active pain-free
      shoulder abduction was decreased. However, isometric shoulder strength test
      showed no differences when compared with pain-free shoulders. Even though the
      pain caused functional problems, the players were still playing with on-going
      symptoms. The diagnoses were mostly unknown, although history and clinical tests
      indicate problems resembling subacromial impingement.

PMID- 16787447
TI  - Reproducibility and relationship of single-joint strength vs multi-joint strength
      and power in aging individuals.
AB  - INTRODUCTION: Reliable and sensitive muscle strength/power assessments are
      essential when evaluating age-related and/or training-induced changes in maximal
      strength and power. AIM: To investigate the reproducibility and inter
      relationship of single-joint isokinetic/isometric leg muscle strength vs multi
      joint mechanical muscle function during counter-movement jump (CMJ) in moderately
      trained aging individuals (age 72.3+/-6.6). RESULTS: The within-subject
      coefficient of variation (CV(w-s)) for the single-joint test showed good
      reproducibility (<10%) for quadriceps and hamstring strength (except for
      hamstring isometric). Plantar flexion demonstrated good to moderate
      reproducibility (CV(w-s) range: 10.4-17.2%). Excellent to good CV(w-s) (<10%) was
      observed for all concentric CMJ parameters, except for plantar flexor mean work
      (CV(w-s)=13%). Eccentric CMJ parameters demonstrated good to moderate
      reproducibility (CV(w-s) range: 8.1-18.2%). Isokinetic and isometric quadriceps,
      hamstring and plantar flexor single-joint strength measurements were found to
      correlate with several CMJ parameters. CONCLUSION: Single-joint and multi-joint
      strength and power assessment tests of the lower limbs appear to be reproducible
      in aging individuals. Furthermore, associations between single-joint strength and
      multi-joint CMJ power and force variables exist. To evaluate functional capacity
      in elderly people further investigations must be carried out to identify specific
      power/strength parameters that are most tightly linked to functional performance.

PMID- 16787448
TI  - Eccentric rehabilitation exercise increases peritendinous type I collagen
      synthesis in humans with Achilles tendinosis.
AB  - It has been shown that 12 weeks of eccentric heavy resistance training can reduce
      pain in runners suffering from chronic Achilles tendinosis, but the mechanism
      behind the effectiveness of this treatment is unknown. The present study
      investigates the local effect of an eccentric training regime on elite soccer
      players suffering from chronic Achilles tendinosis on the turnover of the
      peritendinous connective tissue. Twelve elite male soccer players, of whom six
      suffered from unilateral tendinosis and six were healthy controls, participated
      in this study. All participants performed 12 weeks of heavy-resistance eccentric
      training apart from their regular training and soccer activity. Before and after
      the training period the tissue concentration of indicators of collagen turnover
      was measured by the use of the microdialysis technique. After training, collagen
      synthesis was increased in the initially injured tendon (n=6; carboxyterminal
      propeptide of type I collagen (PICP): pre 3.9+/-2.5 microg/L to post 19.7+/-5.4
      microg/L, P<0.05). The collagen synthesis was unchanged in healthy tendons in
      response to training (n=6; PICP: pre 8.3+/-5.2 microg/L to post 11.5+/-5.0
      microg/L, P>0.05). Collagen degradation, measured as carboxyterminal telopeptide
      region of type I collagen (ICTP), was not affected by training neither in the
      injured nor in the healthy tendons. The clinical effect of the 12 weeks of
      eccentric training was determined by using a standardized loading procedure of
      the Achilles tendons showing a decrease in pain in all the chronic injured
      tendons (VAS before 44+/-9, after 13+/-9; P<0.05), and all subjects were back
      playing soccer following the eccentric training regime. The present study
      demonstrates that chronically injured Achilles tendons respond to 12 weeks of
      eccentric training by increasing collagen synthesis rate. In contrast, the
      collagen metabolism in healthy control tendons seems not to be affected by
      eccentric training. These findings could indicate a relation between collagen
      metabolism and recovery from injury in human tendons.

PMID- 16787449
TI  - Evidence for Golgi-independent transport from the early secretory pathway to the
      plastid in malaria parasites.
AB  - The malaria parasite Plasmodium falciparum harbours a relict plastid (termed the
      apicoplast) that has evolved by secondary endosymbiosis. The apicoplast is
      surrounded by four membranes, the outermost of which is believed to be part of
      the endomembrane system. Nuclear-encoded apicoplast proteins have a two-part N
      terminal extension that is necessary and sufficient for translocation across
      these four membranes. The first domain of this N-terminal extension resembles a
      classical signal peptide and mediates translocation into the secretory pathway,
      whereas the second domain is homologous to plant chloroplast transit peptides and
      is required for the remaining steps of apicoplast targeting. We explored the
      initial, secretory pathway component of this targeting process using green
      fluorescent reporter protein constructs with modified leaders. We exchanged the
      apicoplast signal peptide with signal peptides from other secretory proteins and
      observed correct targeting, demonstrating that apicoplast targeting is initiated
      at the general secretory pathway of P. falciparum. Furthermore, we demonstrate by
      immunofluorescent labelling that the apicoplast resides on a small extension of
      the endoplasmic reticulum (ER) that is separate from the cis-Golgi. To define the
      position of the apicoplast in the endomembrane pathway in relation to the Golgi
      we tracked apicoplast protein targeting in the presence of the secretory
      inhibitor Brefeldin A (BFA), which blocks traffic between the ER and Golgi. We
      observe apicoplast targeting in the presence of BFA despite clear perturbation of
      ER to Golgi traffic by the inhibitor, which suggests that the apicoplast resides
      upstream of the cis-Golgi in the parasite's endomembrane system. The addition of
      an ER retrieval signal (SDEL) - a sequence recognized by the cis-Golgi protein
      ERD2 - to the C-terminus of an apicoplast-targeted protein did not markedly
      affect apicoplast targeting, further demonstrating that the apicoplast is
      upstream of the Golgi. Apicoplast transit peptides are thus dominant over an ER
      retention signal. However, when the transit peptide is rendered non-functional
      (by two point mutations or by complete deletion) SDEL-specific ER retrieval takes
      over, and the fusion protein is localized to the ER. We speculate either that the
      apicoplast in P. falciparum resides within the ER directly in the path of the
      general secretory pathway, or that vesicular trafficking to the apicoplast
      directly exits the ER.

PMID- 16787450
TI  - AUG-proximal nucleotides regulate protein synthesis in Leishmania tropica.
AB  - Gene expression in the Leishmania is controlled post-transcriptionally, and is
      likely to be impacted by both 5' and 3' untranslated regions (UTRs). We have
      investigated the effects of trinucleotides in the AUG-proximal region (APR) (i.e.
      positions -3 to -1 upstream of an AUG) on two reporter genes in the context of an
      endogenous intergenic region of Leishmania tropica. The effects of APRs on
      protein expression were determined in stable transfectants in vivo. Three APRs,
      namely, C(-3)C(-2)C(-1), ACC and GCC, yielded robust translation, whereas GTA
      produced low amounts of proteins. A purine at -3 of an APR was not crucial for
      efficient translation. Steady-state level of reporter mRNA did not correlate
      directly with the amount of protein detected. Polysome analysis revealed that
      APRs modulate translation, at least in part, by influencing mRNA association with
      ribosomes. An analysis of genomic UTRs in L. major showed that (i) the consensus
      APR is N(-3)N(-2)C(-1) (where N = any nucleotide), and (ii) the most frequently
      used APRs include ACA, ACC, ATC, GCC, GCG, GTC and CAC, some of which were
      translation enhancers in our experimental studies.

PMID- 16787451
TI  - Irritants in combination with a synergistic or additive effect on the skin
      response: an overview of tandem irritation studies.
AB  - Sodium lauryl sulfate (SLS) has often been chosen as a model for irritant contact
      dermatitis (ICD) to study the effect of irritants in combination (1-14). Recently
      'tandem', or sequential, exposures with SLS have been performed to study the
      mechanism of skin barrier impairment in ICD (1-6, 15). The assessment of
      reactions have been documented with visual scoring, transepidermal water loss
      (TEWL), skin colour reflectance measurements, skin blood flow; among which TEWL
      has been noted as the most sensitive value (16). The matched control groups were
      treated with either a single exposure to a single irritant or in tandem with the
      same irritant repeatedly. Synergistic and additive effects have been reported for
      various tandem pairs of irritants, however, the mechanism for both remains
      unclear. The results of tandem irritation studies were evaluated to define and
      investigate the responses produced and deduce a possible mechanism of action.
      Clinical ramifications, albeit complex, are discussed.

PMID- 16787452
TI  - Contact allergy to textile dyes in southern Sweden.
AB  - Contact allergy to disperse dyes in textiles is documented in prevalence studies
      from southern Europe. To evaluate the prevalence of allergic patch test reactions
      to different textile dyes in southern Sweden, and to look at the sites of
      dermatitis in individuals hypersensitive to textile dyes, we retrospectively
      investigated 3325 consecutively patch-tested patients. They had all been patch
      tested with the standard test series supplemented with a textile dye mix (TDM)
      consisting of 8 disperse dyes, i.e. Disperse (D) Blue 35, 106 and 124, D Yellow
      3, D Orange 1 and 3 and D Red 1 and 17. All but 3 of the TDM-positive patients
      were additionally tested with the separate dyes included in the mix. The
      frequency of contact allergy to TDM was 1.5%, which is comparable with studies
      from southern Europe. The most common dye allergen was D Orange 1. The high
      prevalence of allergic reactions to D Orange 1 was unexpected, whereas test
      reactions to D Blue 106 and 124 were lower than expected from other studies.
      Compared to all tested patients, the TDM-positive patients more often had
      dermatitis on their arms, face, neck and axillary folds, and women also had a
      higher frequency of hand dermatitis.

PMID- 16787453
TI  - Contact dermatitis from methylisothiazolinone in a paint factory.
AB  - Introduction of new potential contact-sensitizing chemicals have in the past led
      to epidemics of contact dermatitis. A new preservative containing only
      methylisothiazolinone (MI) and not methylchloroisothiazolinone (MCI) has recently
      been introduced in the European Union for use in products, such as paint, glue
      and cosmetics. The objective of this article is to describe a factory outbreak of
      contact allergy to MI and MCI preservatives. This factory outbreak describes
      allergic contact dermatitis towards MI in 4 patients of 14 persons working at a
      paint manufacturer. Patch test results from all patients showed positive
      reactions for MI and MCI/MI. The reactions were stronger for MI than MCI/MI
      indicating a primary sensitization to MI. The combination of MCI/MI remains
      widely used, and therefore various patterns of exposure and sensitization could
      be seen in the future. Our data show that MI holds a potential for eliciting and
      propably inducing contact allergy in humans. Whether this preservative is safe to
      use in cosmetics where billions of consumers are exposed needs a care full
      monitoring.

PMID- 16787454
TI  - Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.
AB  - Little is known about cytokines involved in chronic irritant contact dermatitis.
      Individual cytokine profiles might explain at least part of the differences in
      the individual response to irritation. Our objective was to investigate the
      relation between baseline stratum corneum (SC) cytokine levels and the skin
      response to a single and a repeated irritation test. This study also aimed to
      determine changes in SC cytokine levels after repeated irritation. Transepidermal
      water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr
      exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated
      exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from
      an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)
      1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold
      and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of
      TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed
      barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are
      likely to be indicators of higher skin irritability after single exposure to SLS.
      Barrier repair in some of the subjects might explain the lack of agreement
      between the TEWL response after single and repeated irritation.

PMID- 16787455
TI  - Is the question 'Have you had childhood eczema?' useful for assessing childhood
      atopic eczema in adult population surveys?
AB  - Atopic eczema (AE) is a major risk factor for hand eczema. In Scandinavian
      population-based studies, the occurrence of AE in childhood has often been
      assessed by the question 'Have you had childhood eczema?' In the present study,
      this question was validated. A questionnaire was sent to 600 cases with AE and
      600 controls without eczema or allergic disease, identified in school medical
      records from the 1960s. The response rate was 70.5%, and the mean age of the
      respondents was 36.7 years. The specificity of the question was 70.7% and the
      sensitivity 89.9%. The sensitivity was higher and the specificity lower in a
      subgroup with current hand eczema compared with a group without hand eczema. The
      results showed that the question overestimated the prevalence of AE in childhood
      by a factor of 1.6. When used for risk assessment, the question provided a better
      estimate of the risk of current hand eczema as compared with the lifetime risk of
      hand eczema. In conclusion, the validated question overestimated prevalence of
      childhood AE and may overestimate AE as a risk factor for hand eczema in adult
      population surveys.

PMID- 16787457
TI  - Nickel allergy mimicking basal cell carcinoma.

PMID- 16787456
TI  - White petrolatum (Ph. Eur.) is virtually non-sensitizing. Analysis of IVDK data
      on 80 000 patients tested between 1992 and 2004 and short discussion of
      identification and designation of allergens.
AB  - Sporadic cases of contact allergy to white petrolatum, which is used as a vehicle
      in patch test preparations, have been reported. The quantitative relevance of the
      phenomenon remains yet to be elucidated. METHODS: Retrospective analysis of patch
      test data of the Information Network of Departments of Dermatology (IVDK,
      http://www.ivdk.org) between 1992 and 2004. RESULTS: Analysis of 79 365 patients
      patch tested with pure petrolatum yielded 27 '+' (0.03%) and 2 '+++' (0.003%)
      reactions. The majority of non-negative reactions (0.3%) was interpreted as
      doubtful (235) or mild irritant (32). The negative reaction index (RI) (-0.8),
      and the high positivity ratio (PR) (93%) especially a lack of concordance with
      patch test preparations containing > or=99% petrolatum indicate that many of the
      'positive' (+) reactions have to be considered as irritant. There were 2 '+++'
      reactions. In 1 case, an 'angry back reaction' was confirmed. The other case is
      probably a reading or documentation error, as the majority of patch test
      reactions to preparations containing petrolatum remained negative in this case
      also. CONCLUSIONS: True allergic patch test reactions to white petrolatum are
      extremely rare and probably due to an individually increased susceptibility to
      allergens and/or irritants. This is in agreement with considering petrolatum as a
      non-sensitizer.

PMID- 16787458
TI  - Bikini dermatitis due to mercaptobenzothiazole.

PMID- 16787459
TI  - Allergic contact dermatitis from timolol and dorzolamide eye drops.

PMID- 16787460
TI  - Mastix, a known herbal allergen, as causative agent in occupation-related
      dermatitis.

PMID- 16787461
TI  - Allergic contact dermatitis from iodine in a topical ointment.

PMID- 16787462
TI  - Photoallergic contact dermatitis from topical diclofenac in Solaraze gel.
AB  - Solaraze gel (Shire Deutschland GmbH & Co. KG, Cologne, Germany) containing 3%
      diclofenac has been licensed in 2001 as a topical treatment for actinic
      keratoses. It is commonly used in dermatological practice. Undesirable effects
      are believed to be rare but include pruritus, paresthesia and application-site
      reactions (dry skin, rash, erythema, contact dermatitis and vesicobullous
      eruptions). Recently, a few cases of contact dermatitis due to three different
      allergens including diclofenac have been reported (1,2).

PMID- 16787463
TI  - Decyl glucoside contact allergy from a sunscreen product.

PMID- 16787464
TI  - 2-phenoxyethanol-induced contact urticaria.

PMID- 16787465
TI  - Allergic contact dermatitis mimicking atopic dermatitis due to enoxolone in a
      topical medicament.

PMID- 16787467
TI  - Paths to nursing leadership.
AB  - AIM: The aim was to explore why nurses enter nursing leadership and apply for a
      management position in health care. The study is part of a research programme in
      nursing leadership and evidence-based care. BACKGROUND: Nursing has not invested
      enough in the development of nursing leadership for the development of patient
      care. There is scarce research on nurses' motives and reasons for committing
      themselves to a career in nursing leadership. METHOD: A strategic sample of 68
      Finnish nurse leaders completed a semistructured questionnaire. Analytic
      induction was applied in an attempt to generate a theory. FINDINGS: A theory,
      Paths to Nursing Leadership, is proposed for further research. Four different
      paths were found according to variations between the nurse leaders' education,
      primary commitment and situational factors. They are called the Path of Ideals,
      the Path of Chance, the Career Path and the Temporary Path. CONCLUSION:
      Situational factors and role models of good but also bad nursing leadership
      besides motivational and educational factors have played a significant role when
      Finnish nurses have entered nursing leadership. The educational requirements for
      nurse leaders and recruitment to nursing management positions need serious
      attention in order to develop a competent nursing leadership.

PMID- 16787468
TI  - The perceived problem-solving ability of nurse managers.
AB  - STUDY RATIONALE: The development of a problem-solving approach to nursing has
      been one of the more important changes in nursing during the last decade. Nurse
      Managers need to have effective problem-solving and management skills to be able
      to decrease the cost of the health care and to increase the quality of care.
      STUDY AIM: This descriptive study was conducted to determine the perceived
      problem-solving ability of nurse managers. METHOD: From a population of 87 nurse
      managers, 71 were selected using the stratified random sampling method, 62 nurse
      managers agreed to participate. Data were collected through a questionnaire
      including demographic information and a problem-solving inventory. The problem
      solving inventory was developed by Heppner and Petersen in 1982, and validity and
      readability studies were done. It was adapted to Turkish by Sahin et al (1993).
      The acquired data have been evaluated on the software spss 10.0 programme, using
      percentages, mean values, one-way anova and t-test (independent samples t-test).
      RESULTS: Most of the nurses had 11 or more years of working experience (71%) and
      work as charge nurses in the clinics. It was determined that 69.4% of the nurse
      managers did not have any educational training in administration. The most
      encountered problems stated were issues related to managerial (30.6%) and
      professional staff (25.8%). It was identified that nurse managers who had
      received education about management, following scientific publication and
      scientific meeting and had followed management models, perceived their problem
      resolving skills as more adequate than the others (P>0.05). CONCLUSION: In this
      study, it was determined that nurses do not perceive that they have problem
      solving skills at a desired level. In this context, it is extremely important
      that this subject be given an important place in both nursing education
      curriculum and continuing education programmes.

PMID- 16787469
TI  - Leadership styles in nursing management: preferred and perceived.
AB  - AIM: The aim was to explore nursing leadership regarding what nurse managers and
      subordinates see as important and to explore subordinates' opinions of their
      nurse manager's performance in reality. Background The manager's style can be
      fundamental for subordinates' acceptance of change and in motivating them to
      achieve stated visions and goals and high quality of care. METHODS: Nurse
      managers (n=77) and 10 of each included nurse manager's subordinates received a
      questionnaire to assess 'preferred' leadership behaviour in three dimensions:
      change, production and employee/relation orientations. The same questionnaire was
      used to assess subordinates' opinions of their manager's leadership behaviour.
      RESULTS: There are statistically significant differences in opinions of preferred
      leadership between managers and subordinates, especially related to production
      and relation orientation. The subordinates' perception of real leadership
      behaviour has lower mean values than their preferred leadership behaviour in all
      three dimensions. CONCLUSIONS: Subordinates prefer managers with more clearly
      expressed leadership behaviour than managers themselves prefer and demonstrate.

PMID- 16787470
TI  - 'Let me tell you what I really think about you'--evaluating nursing managers
      using anonymous staff feedback.
AB  - The evaluation of employees by their superiors is standard managerial practice
      but the value of the evaluation of superiors by their employees is much less
      recognized. This study describes a project where for 3 years (2000-02), in an
      Israeli mental health center, the Director of Nursing, clinical supervisors, ward
      head nurses and their deputies were evaluated by nurses and nursing aides.
      Feedback was gathered through anonymous questionnaires under conditions of
      confidentiality. Based on the findings, steps were taken to improve managers'
      performance. Evaluators were also requested to evaluate the project's
      contribution to themselves and the hospital in a second, open questionnaire. All
      parties, evaluators and evaluated, expressed satisfaction and recommended that
      the project continue on a regular basis. Nurses felt empowered and respected and
      that manager-subordinate relations were improved. Other results and
      recommendations are discussed.

PMID- 16787471
TI  - Achieving Magnet accreditation in the UK: a case study at Rochdale NHS Trust.
AB  - AIMS: This study explored the Magnet accreditation process in the first health
      care organization outside the USA to attempt to gain the award, Rochdale NHS
      Trust United Kingdom. The development was supported by the American Nurses
      Credentialing Center as a pilot project and the research conducted as a case
      study in organizational response to the requirements of a new accreditation
      system. METHOD: Information was collected via 23 face-to-face and three telephone
      interviews carried out with 11 senior figures at Rochdale during the 2-year
      period of the Magnet project, from field notes of meetings attended by the
      researchers and from analysis of documents associated with the project. RESULTS:
      The work of applying for Magnet accreditation built upon a previous 2-3 year
      programme of shared governance and clinical leadership throughout the Trust which
      senior staff felt had been an essential foundation for the Magnet project. The
      process enabled staff to assemble evidence which held up a mirror to their
      practice and contributed to other quality-related initiatives. The experience at
      Rochdale suggests that Magnet enables care areas to identify and celebrate
      examples of good practice and for lessons to be learned and shared within the
      organization. Although the Magnet concept is primarily nursing oriented, medical
      and allied health professionals were able to contribute and benefit. The
      application was successful and Rochdale was awarded Magnet status in April 2002.
      CONCLUSIONS: The Magnet project at Rochdale was essentially a process of
      collecting evidence to formally recognize previous leadership initiatives and
      their effects within the organization. The emergent approach to implementing the
      Magnet project was one which attempted to integrate and utilize existing systems
      and resources. The project provides evidence that Magnet can be transferred to
      non-US health care systems. The principal issues associated with this transfer
      were the costs incurred, the interpretation of terminology and the engagement of
      medical and allied health professionals.

PMID- 16787472
TI  - All inclusive benchmarking.
AB  - AIM: The aim of this article is to review published descriptions of benchmarking
      activity and synthesize benchmarking principles to encourage the acceptance and
      use of Essence of Care as a new benchmarking approach to continuous quality
      improvement, and to promote its acceptance as an integral and effective part of
      benchmarking activity in health services. BACKGROUND: The Essence of Care, was
      launched by the Department of Health in England in 2001 to provide a benchmarking
      tool kit to support continuous improvement in the quality of fundamental aspects
      of health care, for example, privacy and dignity, nutrition and hygiene. The tool
      kit is now being effectively used by some frontline staff. However, use is
      inconsistent, with the value of the tool kit, or the support clinical practice
      benchmarking requires to be effective, not always recognized or provided by
      National Health Service managers, who are absorbed with the use of quantitative
      benchmarking approaches and measurability of comparative performance data.
      REVIEW: This review of published benchmarking literature, was obtained through an
      ever-narrowing search strategy commencing from benchmarking within quality
      improvement literature through to benchmarking activity in health services and
      including access to not only published examples of benchmarking approaches and
      models used but the actual consideration of web-based benchmarking data. This
      supported identification of how benchmarking approaches have developed and been
      used, remaining true to the basic benchmarking principles of continuous
      improvement through comparison and sharing (Camp 1989). Descriptions of models
      and exemplars of quantitative and specifically performance benchmarking activity
      in industry abound (Camp 1998), with far fewer examples of more qualitative and
      process benchmarking approaches in use in the public services and then applied to
      the health service (Bullivant 1998). The literature is also in the main
      descriptive in its support of the effectiveness of benchmarking activity and
      although this does not seem to have restricted its popularity in quantitative
      activity, reticence about the value of the more qualitative approaches, for
      example Essence of Care, needs to be overcome in order to improve the quality of
      patient care and experiences. KEY ISSUES: The perceived immeasurability and
      subjectivity of Essence of Care and clinical practice benchmarks means that these
      benchmarking approaches are not always accepted or supported by health service
      organizations as valid benchmarking activity. CONCLUSIONS: In conclusion, Essence
      of Care benchmarking is a sophisticated clinical practice benchmarking approach
      which needs to be accepted as an integral part of health service benchmarking
      activity to support improvement in the quality of patient care and experiences.

PMID- 16787473
TI  - Operational competency development in E and F grade nursing staff: preparation
      for management.
AB  - There is limited literature for operational management competency development in
      E and F grade nursing staff. These grades of nursing staff have to take over from
      G grade nurses ward managers on a regular basis. With human resources doing less
      of the operational management and taking more of an advisory role, nursing staff
      are now required to deal with disciplinary procedures and other management issues
      in a more consistent manner. Therefore, this development programme in a Scottish
      primary care NHS psychiatric service was designed to enable E and F grade nurses
      to take over from ward managers and to enable ward managers to 'succession plan'
      for times when they will be absent. The literature is reviewed, the background to
      the development programme described and the design of the development programme
      is explained. The results from both the pilot study (n=13) and first group (n=8)
      through the course are presented, evaluated discussed.

PMID- 16787474
TI  - A unit-based protocol to enhance Jordanian nurses' autonomous decision making.
AB  - AIM: To develop a unit-based protocol to enhance Jordanian nurses' autonomous
      decision making. BACKGROUND: Many escalating changes are influencing health care
      organizations, which require the enhancement of nurses' autonomy to manage these
      frequent changes. Autonomy is addressed in the context of accountability,
      authority and responsibility. Nurses' involvement in patient care and unit
      operation decisions is a part of their autonomy. Autonomy will influence nurses'
      job satisfaction and retention, patients' satisfaction and the quality of nursing
      care. METHODS: This protocol was developed based on a personal experience, nurses
      and senior nursing students' feedback, a review of the literature, and
      consultation with a group of 26 nurses in a teaching hospital. The nurses were
      asked on the comprehensiveness and applicability of the protocol to health care
      settings. Nurses' suggestions regarding the protocol were taken into
      consideration during the development and revision stages. RESULTS AND
      CONCLUSIONS: A unit-based protocol was developed to enhance nurses' autonomous
      decision making through activities that support the process of autonomy and work
      environment. This protocol will have positive short, intermediate and long-term
      outcomes for patients, nurses and organizations.

PMID- 16787475
TI  - Matching nurse skill with patient acuity in the intensive care units: a risk
      management mandate.
AB  - AIM: This paper aims to highlight the need for the traditional concept of nursing
      skill mix to be reconfigured within a new concept of skill matching. BACKGROUND:
      Substantive literature describes staff deployment and patient-dependency models.
      However, limited information exists as to what informs decision making regarding
      nurse skill assessment and subsequent patient allocation in intensive care units.
      KEY ISSUES: In intensive care units, nurse numbers, available nursing skills and
      patient allocation decisions, impact directly on care provision and outcomes.
      This paper argues that staffing decisions that are based on insufficient
      knowledge which lack consideration of all pertinent factors result in poor 'skill
      matching', potential adverse events and poor outcomes. A critical inextricable
      link exists between staffing decisions, patient safety and risk in the intensive
      care unit. Use of a multifactorial skill-matching approach within a dedicated
      staffing decision-support system is recommended. CONCLUSION: This commentary
      paper adds a new perspective to nurse-staffing decision practices and their
      relationship to risk management in the intensive care unit and offers a new
      research direction.

PMID- 16787476
TI  - Nurses' lived experiences of moral stress support in the intensive care context.
AB  - The aim of this study was to analyse and describe lived experiences of support in
      situations characterized by critical care situations and moral stress in
      intensive care nursing. An exploratory interpretative study was conducted. Data
      consisted of interviews with 36 nurses from different types of intensive care
      units. The first level of analysis of data identified contextual factors, such as
      type and purpose of support and working conditions. On the next level of analysis
      five tentative interpretations were identified: (1) receiving organized support
      is a matter of self-determination, (2) whether to participate in organized
      support or to be off duty are experienced as mutually exclusive, (3) dealing with
      moral stress is experienced as a private matter, (4) colleagues managing moral
      stress serve as models in stress support and (5) not being able to deal with
      moral stress urges one to seek outside support. A comparison of these
      interpretations identified three major themes: availability, accessibility and
      receptivity of support. The main interpretation and conclusion were: lived
      experience of moral stress support involves an interconnectedness between
      structural and existential factors. Thus, adequate moral stress support
      presupposes an allowable professional climate and access to caring supervision.

PMID- 16787477
TI  - Situations influencing habits in diet and exercise among nurses working night
      shift.
AB  - OBJECTIVES: The aim of the investigation was to describe situations with a
      significant influence on healthy diet and exercise habits among nurses working
      night shift. METHODS: A qualitative descriptive design with a Critical Incident
      Technique approach was used. Situations were collected by means of interviews
      with 27 registered/enrolled community nurses. RESULTS: A total of 143 situations
      were identified comprising two main areas: coping ability at work and coping
      ability during leisure hours. Coping ability at work included 81 critical
      incidents grouped into two categories: the nurses' diet and exercise habits were
      influenced by social interaction with colleagues at work and by the disruption to
      their circadian rhythm. Coping ability during leisure hours included 62 critical
      incidents grouped into two categories: the diet and exercise habits were
      influenced when the nurses recovered from the disruption to their circadian
      rhythm and when they took advantage of the freedom of action offered by night
      work. CONCLUSIONS: By identifying the factors that influence diet and exercise
      habits among nurses working night shift, strategies can be developed in order to
      strengthen the factors with a positive influence.

PMID- 16787478
TI  - Guest editorial: health and social care for environmental health - realigning
      geographical traditions.

PMID- 16787479
TI  - Barriers and strategies affecting the utilisation of primary preventive services
      for people with physical disabilities: a qualitative inquiry.
AB  - Individuals with physical disabilities are less likely to utilise primary
      preventive healthcare services than the general population. At the same time they
      are at greater risk for secondary conditions and as likely as the general
      population to engage in health risk behaviours. This qualitative exploratory
      study had two principal objectives: (1) to investigate access barriers to
      obtaining preventive healthcare services for adults with physical disabilities
      and (2) to identify strategies to increase access to these services. We conducted
      five focus group interviews with adults (median age: 46) with various physically
      disabling conditions. Most participants were male Caucasians residing in
      Virginia, USA. Study participants reported a variety of barriers that prevented
      them from receiving the primary preventive services commonly recommended by the
      US Preventive Services Task Force. We used a health services framework to
      distinguish structural-environmental (to include inaccessible facilities and
      examination equipment) or process barriers (to include a lack of disability
      related provider knowledge, respect, and skilled assistance during office
      visits). Participants suggested a range of strategies to address these barriers
      including disability-specific continuing education for providers, the development
      of accessible prevention-focused information portals for people with physical
      disabilities, and consumer self-education, and assertiveness in requesting
      recommended services. Study findings point to the need for a more responsive
      healthcare system to effectively meet the primary prevention needs of people with
      physical disabilities. The authors propose the development of a consumer- and
      provider-focused resource and information kit that reflects the strategies that
      were suggested by study participants.

PMID- 16787480
TI  - Should uptake of state benefits be used as indicators of need and disadvantage?
AB  - Government requires indicators of disadvantage to guide programmes and allocate
      resources to those areas which are most in need. Proxy measures of relative
      disadvantage are often utilised for this task in the absence of ideal indicators
      of need. The recent availability of government administrative datasets, such as
      social security benefit uptake levels, are increasingly being used throughout the
      UK and have been hailed as a significant advance on previous measures of need.
      However, their suitability presupposes that the association between those in need
      of benefit and those actually in receipt of benefit is not confounded by non
      needs-related factors. In the present study, the authors examine area-level
      factors associated with uptake of one health-related benefit and show that, while
      closely correlated with health status, it is also associated with factors which
      might be related to the propensity and ability to make a successful claim, as
      well as local adjudication practices. They conclude that, while the use of these
      government datasets has increased our ability to target resources, researchers
      and policy makers should be aware of these additional influences.

PMID- 16787481
TI  - The complementarity norm: service provision by the welfare state and voluntary
      organisations in Sweden.
AB  - Previous research has shown that different providers of social welfare tend to
      provide complementary services at a local level, but that there is no complete
      task specialisation. This means that elements of complementarity theory are
      challenged, especially the so-called 'principle of matching', i.e. that actors
      only undertake tasks which match their characteristics. The aim of the present
      study was to explore complementarity between Swedish local authorities and
      voluntary organisations in their support for relatives of older people.
      Interviews were carried out with 55 politicians, civil servants and
      representatives of voluntary organisations drawn from four municipalities. These
      municipalities were selected from a sampling frame that ensured representation of
      different combinations of high and low levels of voluntary and statutory
      services. Qualitative analysis of interview transcripts showed that, while local
      authorities are seen as responsible for the support for relatives, voluntary
      organisations are expected to be complementary, offering 'the icing on the cake',
      i.e. social support and activities which are regarded as less demanding. Overall,
      substantial support for a norm of complementarity was found. It is argued that,
      if those who are active in social policy and voluntary work at a local level
      agree with the ideal of complementarity, this will influence their wish to
      arrange activities and services. Therefore, the complementarity norm - rather
      than the principle of matching - influences the outcome in terms of service
      provision.

PMID- 16787482
TI  - Caring for a young adult with cancer: the impact on mothers' health.
AB  - That the carers of people with cancer are profoundly affected by their caring
      role is well established, yet the needs of one particular cohort, i.e. the
      parents of young adults with cancer, have not been well understood. The majority
      of carers in this situation are mothers, and it is the impact of the emotional
      and physical labour entailed by the care of young adults that is the focus of the
      present paper. Through the analysis of qualitative narrative data contributed by
      the mothers of young adults with cancer, the aim of this paper is to examine the
      health effects for women of caring for a young adult son or daughter with a life
      threatening illness. The results suggest that there is an impact on the mother's
      health that results in unspecific, low-grade and chronic psychological and
      somatic symptoms which the mothers rank as a low priority. The mothers' attempts
      to appear to be managing may serve to mask their own health needs from health
      professionals whose primary concern is the health of the son or daughter. Where
      psychological distress is admitted, the resulting use of prescribed
      antidepressants may not be experienced as helpful. The conclusions are that,
      because of the particular circumstances of caring for a young adult son or
      daughter with cancer, health professionals' attention to the mothers' health
      throughout the cancer journey may act as a preventative measure for later and
      more serious ill health.

PMID- 16787483
TI  - Homelessness among problem drug users: prevalence, risk factors and trigger
      events.
AB  - The present paper uses data from a prospective cohort study of 877 problem drug
      users entering treatment in Scotland to extend knowledge of homelessness and drug
      misuse in three important respects: First, the prevalence of homelessness among
      problem drug users is investigated; secondly, key risk factors for homelessness
      among problem drug users are identified; and thirdly, trigger events associated
      with movements into or out of homelessness by problem drug users over time are
      explored. Data were collected during two waves of interviewing which were
      conducted 8 months apart. Thirty-six per cent of problem drug users entering
      treatment were homeless at either or both interviews, a prevalence rate that is
      at least seven times greater than among the general population. Whilst many of
      the risk factors found to be associated with homelessness are common to homeless
      people in general, at least one homelessness risk factor - recent drug injection
      [OR = 1.40; 95% confidence interval (CI) = 1.01-1.96]- is clearly specific to
      those who take drugs. Movements into homelessness among problem drug users were
      associated with recently losing residency of children (OR = 2.28; 95% CI = 1.27
      4.08), other recent family problems (OR = 1.88; 95% CI = 1.21-2.94) and worsening
      general health (OR = 2.17; 95% CI = 1.15-4.09). Movements out of homelessness
      were associated with not having recent family problems (OR = 0.43; 95% CI = 0.24
      0.79). The findings provide empirical support for the good practice guidelines
      now being published by various UK Government departments, but also suggest that
      the relatives of problem drug users should be offered increased assistance to
      help them deal with the many stresses that having a drug-dependent family member
      can bring.

PMID- 16787484
TI  - Immigrant women family caregivers in Canada: implications for policies and
      programmes in health and social sectors.
AB  - Migration has become a profound global phenomenon in this century. In Canada,
      uncoordinated policies, including those related to immigration, resettlement,
      employment, and government funding for health and social services, present
      barriers to immigrant women caregivers. The purpose of this paper is to share
      relevant insights from individual and group interviews with immigrant women
      family caregivers, service providers and policy influencers, and discuss these in
      relation to immigration, health and social policy, and programme trends in
      Canada. The present authors conducted individual interviews with immigrant women
      family caregivers (n = 29) in phase 1, followed by two group interviews with
      women family caregivers (n = 7), and two group interviews with service providers
      and policy-makers (n = 15) in phase 2. Using an inductive approach, the authors
      employed thematic content data analysis. Immigrant women experienced barriers to
      health and social services similar to Canadian-born family caregivers,
      particularly those who have low incomes, jobs with limited flexibility and heavy
      caregiving demands. These immigrant women family caregivers avoided certain
      formal services for a variety of reasons, including lack of cultural sensitivity.
      However, their challenges were compounded by language, immigration and separation
      from family in the home country. The identified barriers to support reinforce the
      importance of modifying and expanding policies and programmes affecting immigrant
      women's ability to care for family members with illnesses or disabilities within
      the context of Canadian society. Participants recommended changes to policies and
      programmes to deal with information, transportation, language, attitudinal and
      network barriers. The various barriers to services and programmes which were
      experienced by immigrant women caregivers underscore the importance of reviewing
      policies affecting immigration, caregiving, and access to health and social
      services. Intersectoral collaboration among agencies is essential to reduce the
      barriers identified in the present study, and to establish services which are
      linguistically and culturally appropriate.

PMID- 16787485
TI  - A survey of end-of-life care in care homes: issues of definition and practice.
AB  - Care homes throughout the UK provide long-term care for frail older people.
      Whilst care homes are a home for life, many of the older people living in this
      setting also die there. There is increased interest in improving the care that
      older people receive in care homes towards the end of life. One way to achieve
      this has been through links with specialist palliative care services. The
      knowledge held in care homes by staff, residents and their family carers has yet
      to be fully integrated into this work. Consequently, a postal survey of care home
      managers in one English county was undertaken to examine the characteristics of
      end-of-life care for older people in these care homes. We sought to establish the
      managers' understanding of end-of-life care; the extent to which dying and death
      is present in this setting; the attributes of the resident population living in
      these care homes; and the availability of resources to support the provision of
      end-of-life care in this setting. The survey identified that managers held
      diverse understandings regarding the meaning of end-of-life care. The features of
      the residents' conditions and the dying that they experience requires a different
      way to conceptualise end-of-life care. A longer-term perspective is offered here
      that encompasses the whole period of a person's residence in a care home.

PMID- 16787486
TI  - Falling through the net of stroke care.
AB  - The provision of healthcare services has been shown to differ by social
      characteristics such as gender, age and social status. The processes by which
      such differences arise are unclear. We report findings from a qualitative
      interview study with stroke service providers undertaken during an investigation
      of inequalities in stroke care. We interviewed 41 professionals from hospital and
      community settings in south London. Participants' accounts are used to explore
      how it is that patients' trajectories of care might not follow evidence-based
      guidelines, focusing on stroke unit admission, provision of hospital
      rehabilitation therapies and community health and social services. Categories of
      patients who might not receive best care were people who were cognitively
      impaired, those regarded as having 'complex problems', those with communication
      problems and younger people. Additionally, the local availability of services was
      thought to affect individuals' chances of receiving particular components of
      care. Although professionals spoke of certain types of patients as 'falling
      through the net' (of services), their accounts suggest that they channel patients
      through services according to an implicit template of the individual suited to
      the service. Those who do not fit the service as currently resourced may have
      reduced access to specific components of care. If inequalities in access to care
      are to be addressed we require a better understanding of how professionals'
      decision-making processes test the fit between service users and the implicit
      template of 'suitable' patient or client.

PMID- 16787487
TI  - Carers and confidentiality in mental health care: considering the role of the
      carer's assessment: a study of service users', carers' and practitioners' views.
AB  - Relatives or carers of people with mental health problems have criticised
      professionals for their failures to share information with them. This article
      reports on a multiple method study comprising a policy search, a survey of
      service users, carers and professionals, and stakeholder interviews and group
      events. The study found few policies that addressed the principles underpinning
      information sharing with carers. However, examples of good practice in
      professional involvement of carers that took account of carer rights and
      responsibilities emerged from the research. This suggests the relevance of the
      carer's assessment, a carer's right to an assessment of his or her circumstances
      and wishes in assisting understanding of the care context and enhancing
      appropriate information sharing between professionals and carers.

PMID- 16787494
TI  - Metastatic melanoma.

PMID- 16787495
TI  - Structural analogues of AMD3100 mobilise haematopoietic progenitor cells from
      bone marrow in vivo according to their ability to inhibit CXCL12 binding to CXCR4
      in vitro.
AB  - The CXCR4 antagonist, AMD3100, stimulates a rapid increase in circulating numbers
      of haematopoeitic progenitor cells (HPCs) in both mice and human healthy
      volunteers. An in situ perfusion system of the mouse femoral bone marrow was used
      to provide the first direct evidence that AMD3100 mobilises HPCs from the bone
      marrow. Structural analogues of AMD3100 demonstrated that the ability of these
      compounds to mobilise HPCs in vivo correlated with their capacity to antagonise
      CXCR4 in vitro. This model system was also used to demonstrate additive effects
      of AMD3100 administered acutely, with granulocyte colony-stimulating factor
      administered chronically, with respect to HPC mobilisation.

PMID- 16787496
TI  - Incidence of invasive fungal infection in adult haematological malignancy: a
      prospective validation of a risk stratification scheme.

PMID- 16787497
TI  - Manipulation of prothrombin concentration improves response to high-dose factor
      VIIa in a cell-based model of haemophilia.
AB  - Clinical reports suggest that treatment regimens employing both activated
      prothrombin complex concentrates (aPCCs) and recombinant activated factor VII
      (rFVIIa) may control the bleeding in patients with haemophilia who fail to
      respond to either agent alone. We hypothesised that increased concentrations of
      prothrombin, as may be observed after the infusion of aPCCs, favourably influence
      parameters of thrombin generation in haemophilia treated with high-dose rFVIIa.
      We examined the effect of varied prothrombin and rFVIIa concentrations on
      thrombin generation in a model of haemophilia. At all concentrations of rFVIIa,
      increased prothrombin concentrations led to increases in the peak and rate of
      thrombin generation. In assays with the highest concentrations of prothrombin and
      rFVIIa, peak thrombin actually equalled that measured in the model of normal
      haemostasis. The significant impact of prothrombin concentration on the effect of
      rFVIIa in vitro may explain the improved haemostasis reported with concurrent use
      of aPCCs and rFVIIa. These results imply that persons with plasma prothrombin
      levels at either end of the 'normal' range could have significantly different
      responses to similar rFVIIa doses. Furthermore, these results suggest that
      increasing plasma prothrombin concentration prior to rFVIIa administration may
      offer advantages over the use of rFVIIa alone in the treatment of haemophilic
      bleeding.

PMID- 16787498
TI  - Sequential fluorescence in situ hybridisation analysis for cryptic
      t(11;14)(q13;q32) in mantle cell lymphoma.

PMID- 16787499
TI  - Plasmacytoma in a multiple myeloma patient.

PMID- 16787500
TI  - Hemizygous/homozygous and heterozygous JAK2 mutation detected in plasma of
      patients with myeloproliferative diseases: correlation with clinical behaviour.

PMID- 16787502
TI  - Ringed sideroblasts with thrombocytosis: an uncommon mixed
      myelodysplastic/myeloproliferative disease in older adults.

PMID- 16787503
TI  - Serial determination of FLT3 mutations in myelodysplastic syndrome patients at
      diagnosis, follow up or acute myeloid leukaemia transformation: incidence and
      their prognostic significance.
AB  - The incidence of FLT3 mutations (internal tandem duplication and Asp835) was
      investigated in bone marrow samples from 97 patients with myelodysplastic
      syndrome [(MDS); excluding cases with refractory anaemia with excess blasts in
      transformation] at the time of diagnosis and several time points thereafter.
      Three patients had FLT3 mutations at presentation. Forty-two patients progressed
      to acute myeloid leukaemia (AML), including the three patients with FLT3
      mutations at MDS diagnosis. Three additional patients acquired FLT3 mutations and
      progressed to AML in 1 month. FLT3 mutations seem to be a critical additional
      genetic event that transforms a minority of MDS patients to AML.

PMID- 16787504
TI  - Proteasome inhibition as novel treatment strategy in leukaemia.
AB  - Following its success in multiple myeloma (MM), proteasome inhibition has become
      a topic of interest as novel treatment strategy of cancer. By simultaneously
      affecting multiple pathways in the cancer cell, such as deregulation of the
      programmed degradation of many cellular proteins, proteasome inhibition causes
      rapid apoptosis of these cells. Both in rapidly proliferating leukaemic cell
      lines and in primary leukaemic cells isolated from patients, proteasome
      inhibition results in antileukaemic activity. The normal counterparts of these
      cells are much more resistant to proteasome inhibitors (PI), thereby resulting in
      a favourable therapeutic index. Importantly, while leukaemic stem cells are
      sensitive to proteasome inhibition, normal haematopoietic stem cells are still
      viable after drug exposure. Nowadays, many PIs are being identified; bortezomib
      is the most well known since obtaining Food and Drug Administration approval for
      clinical use in MM. This review summarises the biological and clinical aspects of
      proteasome inhibition and discusses the potential role of these inhibitors in the
      treatment of leukaemia.

PMID- 16787506
TI  - Characterization of cells of the B lineage in the human adult greater omentum.
AB  - Peritoneal B cells and their omental precursors play an important role in the
      immune response of the peritoneal cavity and mucosal surfaces in mice. We have
      previously shown that peritoneal and mucosal B lineage cells are unlikely to be
      significantly linked in humans. However, the status of the omentum remains
      unknown. Here, using immunohistochemistry, we observed that sparse, quiescent B
      cells and occasional clusters of B cells were present in the omentum and that
      plasma cells, predominantly with cytoplasmic immunoglobulin G (IgG), were
      present. We analysed sequences of immunoglobulin genes amplified using reverse
      transcriptase-polymerase chain reaction (RT-PCR) from the normal human greater
      omentum, and describe the characteristics of variable region genes used by IgG,
      IgA and IgM. We focused on the properties of IgVH4 and IgVH5 families to allow
      comparisons of like with like between different Ig isotypes and cells from
      different immune compartments. We observed that the IgM genes were derived from a
      mixed population with mutated and unmutated immunoglobulin sequences. All IgVH4
      and IgVH5 genes used by IgA and IgG from omental cells showed evidence of somatic
      hypermutation but the load of mutations was not significantly different to that
      seen in either the systemic or the mucosal compartments. The trends observed,
      including the dominance of IgG plasma cells, the IgA1/IgA2 ratio being biased
      towards IgA1, JH1 usage, and a moderate level of somatic mutations, link omental
      B lineage cells with the systemic compartment. These observations reinforce
      previous studies highlighting the difference between human and murine B-cell
      compartments and their relationship to the mucosal immune system.

PMID- 16787507
TI  - Interventions for treating the posterior interosseus nerve syndrome: a systematic
      review of observational studies.
AB  - For the posterior interosseus nerve syndrome (PINS), no randomised controlled
      trials or controlled clinical trials about the effectiveness of interventions are
      available; only case series can be found. Although the validity of case series is
      inferior to controlled trials, they may provide valuable data about the efficacy
      of treatment options. Therefore, we systematically reviewed all available
      observational studies on treatment of PINS. A literature search and additional
      reference checking was done. On the basis of previous checklists, we constructed
      a quality assessment and rating system to analyse the included case series.
      Studies with less than 50% of the maximum points on the methodological quality
      assessment were excluded from the analysis. The results are summarised according
      to a rating system for the strength of the scientific evidence. Six eligible case
      series for this review were found. After the data extraction and methodological
      quality assessment, two higher quality studies that evaluated the effectiveness
      of surgical decompression of the PIN were included in the final analysis. There
      is a tendency for the effectiveness of surgical decompression of the PIN in
      patients with PINS. The effectiveness of a conservative treatment for PINS is
      unknown because no higher quality studies are available. Additional high-quality
      controlled studies are needed to assess the level of 'conclusive evidence' for
      surgical treatment. There is also a need for high-quality controlled trials into
      the effectiveness of conservative treatments for PINS.

PMID- 16787508
TI  - Sex-dimorphic effects of progesterone and its reduced metabolites on gene
      expression of myelin proteins by rat Schwann cells.
AB  - Data obtained in our and other laboratories have indicated that progesterone (P)
      and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP),
      stimulate the expression of two myelin proteins of the peripheral nervous system
      (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)]. We
      have now considered the effects of P and its derivatives on these and other
      myelin proteins [i.e., myelin-associated glycoprotein (MAG) and myelin and
      lymphocyte protein (MAL)] in sex-specific cultures of rat Schwann cells. Gene
      expression of myelin proteins was assessed by RNase protection assay. Treatment
      with P or DHP induced a stimulatory effect on P0 mRNA levels in male but not in
      female Schwann cells. In contrast, treatment with THP increased gene expression
      of P0 exclusively in female Schwann cells. A similar sex-difference was also
      evident for other myelin proteins. Indeed, PMP22 expression was stimulated by
      treatment with P in male cultures, whereas THP induced an increase of mRNA levels
      in female cultures. Moreover, MAG was stimulated by THP treatment in male
      cultures only, whereas MAL expression was unaffected by neuroactive steroid
      treatment in both male and female cultures. In conclusion, the present
      observations indicate that the effects of neuroactive steroids on myelin proteins
      are sexually dimorphic. This finding might represent an important background for
      sex-specific therapies of acquired and inherited peripheral neuropathies.

PMID- 16787509
TI  - Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood
      flow after topical capsaicin.
AB  - Fabry disease is a rare X-linked lysosomal storage disorder. The mutations result
      in a deficiency of the lysosomal enzyme alpha-galactosidase A causing
      accumulation of glycosphingolipids in the vascular endothelial cells and many
      other tissues. Given the X-linked inheritance, male patients are severely
      affected. Recently, attention has been drawn to female patients whether they also
      show signs of nerve involvement. An early sign of the disease is painful small
      fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction
      in female Fabry patients by using capsaicin applied topically. The response to
      capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry
      patients had a significantly smaller increase in blood flow (p = 0.0003) after
      capsaicin application. The area of static mechanical allodynia and dynamic
      mechanical hyperalgesia was also significantly smaller (p = 0.006) in female
      Fabry patients. This indicates that female Fabry patients have a significant loss
      of small-fibre function and demonstrates that it is possible to evaluate this by
      a non-invasive method.

PMID- 16787510
TI  - Recovery of neurophysiological features with time after rat sciatic nerve repair:
      a magneto-neurographic study.
AB  - Experimental assessment of peripheral nerve regeneration in rats by
      electrophysiology is controversial due to low reproducibility of
      electrophysiological indicators and diminished quantitative evaluation in
      conventional experimental set-ups. Magnetoneurography (MNG) counteracts these
      drawbacks by magnetically recording electrophysiological signals ex vivo, thereby
      providing accurate and quantitative data. In 50 rats, sciatic nerve transection
      was followed by direct repair. MNG outcome parameters, footprints [static toe
      spread factor (TSF); function] and muscle weight (MW) were studied for their
      recovery pattern from 2 to 24 weeks. By using MNG, we showed that the
      regeneration process still continues when functional recovery (static TSF)
      becomes stagnant. With regression analysis, MNG parameters amplitude, amplitude
      area and conduction velocity (CV) demonstrated moderate significant correlation
      with MW, whereas CV was not significantly associated with static TSF. No
      significant association exists between MW and static TSF. A Kaplan-Meier survival
      curve revealed that autotomy/contracture of rat hind paws was not related to
      decreased MNG outcome values. In conclusion, this study highlights and discusses
      the dissimilarities between direct (MNG) and indirect (static TSF and MW)
      assessment techniques of the regeneration process. We emphasise the significance
      of MNG as a direct derivative of axon regeneration in experimental rat studies.
      Additionally, we stress the must for right-left ratios, as neurophysiological
      indicators vary with age, and we confute possible bias in footprint analysis
      caused by exclusion of autotomy/contracture animals.

PMID- 16787511
TI  - Multi-center assessment of the Total Neuropathy Score for chemotherapy-induced
      peripheral neurotoxicity.
AB  - The aim of this multi-center study was to assess with reduced versions of the
      Total Neuropathy Score (TNS), the severity of chemotherapy-induced peripheral
      neurotoxicity (CIPN), and to compare the results with those obtained with common
      toxicity scales. An unselected population of 428 cancer patients was evaluated at
      11 different centers using a composite (clinical + neurophysiological, TNSr) or
      clinical (TNSc) examination and with the National Cancer Institute - Common
      Toxicity Criteria (NCI-CTC) 2.0 and Eastern Cooperative Oncology Group (ECOG)
      scores. A highly significant correlation was demonstrated between the TNSr and
      the NCI-CTC 2.0 and ECOG scores; but the TNSr evaluation was more accurate in
      view of the more extended score range. Also, the simpler and faster TNSc (based
      only on the clinical neurological examination) allowed to grade accurately CIPN
      and correlated with the common toxicity scores. The correlation tended to be
      closer when the sensory items were considered, but also the TNSr motor items,
      which were not specifically investigated in any other previous study,
      significantly correlated with the results of the common toxicity scales. In
      conclusion, this study suggests that the TNSr is a reliable tool for accurately
      grading and reporting CIPN, with the additional and so far unique support of a
      formal comparison with known and widely used common toxicity scales. The TNSc is
      a valid alternative if neurophysiological examination is not feasible. The longer
      time needed to calculate the TNSr and TNSc in comparison to the ECOG or the NCI
      CTC 2.0 scales is offset by the more detailed knowledge of the CIPN
      characteristics.

PMID- 16787512
TI  - Collateral sprouting of human epidermal nerve fibers following intracutaneous
      axotomy.
AB  - Despite the clinical need, there are no therapeutic compounds available to
      promote peripheral nerve regeneration. In part, this may be due to a lack of
      sensitive measures of nerve growth. Here, we describe a novel approach of
      measuring collateral sprouting of epidermal nerve fibers (ENF) in human subjects
      and describe the effect of the neuroimmunophilin ligand timcodar dimesylate on
      collateral nerve sprouting. The objective of this study was to describe a model
      of intracutaneous axotomy and evaluate the ability of timcodar dimesylate to
      accelerate human cutaneous nerve regeneration through collateral sprouting.
      Subjects were randomized to receive placebo, 12.5 or 50 mg/day timcodar
      dimesylate in a prospective, two-center, double-blind, placebo-controlled trial.
      A 3-mm distal thigh punch skin biopsy was performed at baseline, and a 4-mm
      overlapping concentric biopsy was taken after 56 days of treatment. Biopsies were
      processed to visualize ENF, and the collateral sprouting distance (CSD) was
      measured. Sixty-two subjects completed the trial, and the CSD was measurable in
      52. The CSD (mean +/- SEM) was 474.5 microm +/- 38.3, 473.4 microm +/- 28.4, and
      450.8 microm +/- 26.5 for the placebo, low and high dose groups, respectively (p
      = 0.84). The baseline ENF density was associated with the CSD (p = 0.02).
      Collateral sprouting was efficiently measured using an intracutaneous axotomy
      model and suggests a collateral sprouting rate of 8.5 microm/day in healthy
      subjects. The model was consistent across treatment groups and had a low
      coefficient of variation. Timcodar dimesylate treatment was safe over an 8-week
      period but did not improve collateral sprouting among healthy subjects.

PMID- 16787514
TI  - Galanin receptor expression in cultured human keratinocytes and in normal human
      skin.
AB  - Galanin (GAL) is a biologically active neuropeptide that is widely distributed in
      the nervous system. GAL exerts diverse action via the GAL receptors (GALR1,
      GALR2, and GALR3), which belong in the superfamily of G-protein-coupled
      transmembrane receptors. In human skin, GAL-like immunoreactivity has been
      reported in free nerve endings and fibers of the dermis. The extraneuronal
      expression of GAL has also been demonstrated. Although the GALRs are essential
      for biological functions, the expressions of different GALR subtypes in cultured
      human keratinocytes have not yet been investigated. The aim of our study was to
      investigate the mRNA and protein expressions of the different GALRs in the HaCaT
      immortalized keratinocyte cell line and in cultured human keratinocytes. When
      reverse transcription (RT)-polymerase chain reaction (PCR) was used with
      different GALR-specific primers, only GALR2 mRNA was identified in cultured HaCaT
      cells and keratinocytes. Sequencing of the PCR products proved the presence of
      GALR2 mRNA in the keratinocytes. The presence of GALR2 protein was next
      investigated, using a polyclonal antibody against human GALR2. Both the HaCaT
      cells and the cultured keratinocytes displayed specific immunohistochemical
      staining, with higher intensity on the surface of the keratinocytes.
      Immunohistochemical investigations of normal human skin specimens revealed that
      GALR2 was expressed with high intensity in the basal layer of the epidermis and
      also around the hair follicles in the dermis. GAL treatment of the keratinocytes
      resulted in an increase in cytosolic Ca2+ concentration, suggesting that GALR2 is
      a functional receptor. Further studies are necessary to clarify the biological
      effects of GAL in the skin.

PMID- 16787513
TI  - SIMPLE mutation analysis in dominant demyelinating Charcot-Marie-Tooth disease:
      three novel mutations.
AB  - Charcot-Marie-Tooth disease type 1C (CMT1C) is caused by mutations in the small
      integral membrane protein of the lysosome/late endosome (SIMPLE). We analyzed the
      coding sequence of SIMPLE in DNA of 53 unrelated cases of dominant demyelinating
      CMT disease with no mutations in PMP22, GJB1, MPZ, EGR2, and NEFL genes. Four
      different missense mutations were observed in six families. The mutation
      Gly112Ser was found in two families confirming its frequent occurrence in SIMPLE
      mutations. Three novel mutations were also identified: Ala111Gly (two families),
      Pro135Ser, and Pro135Thr. Familial studies revealed that all carriers of
      mutations (n = 38), aged from 1 to 78 years, were symptomatic, notably children
      under 10 years (n = 8). Motor conduction velocities in the median nerve ranked
      from 16.4 to 32.8 m/s (n = 20). In our series of 968 unrelated dominant
      demyelinating CMT cases (1992-2005), the percentage of SIMPLE mutations was 0.6
      (6/968).

PMID- 16787515
TI  - Nerve injuries following intramuscular injections: a clinical and
      neurophysiological study from Northwest India.
AB  - In developing countries, injections are frequently used to treat common ailments.
      Intramuscular injections (IMI) may damage peripheral nerves at the site of
      injection. Our objectives were to study the clinical features, neurophysiological
      findings, and outcome in patients with nerve injuries (NI) following IMI and to
      determine the factors affecting prognosis. We conducted a retrospective review of
      patients with NI following IMI, who were referred to our Neurophysiology
      Laboratory at Christian Medical College, Ludhiana, India, between January 1990 to
      December 2003. There were 36 (55%) patients with sciatic nerve palsy, 29 (44%)
      patients with radial nerve injury, and 1 (1%) patient with posterior femoral
      cutaneous nerve injury. In 57 (86%) patients, the IMI were given by uncertified
      medical practitioners. Needle electromyography (EMG) was analyzed in 36 patients
      (>or=60 days after onset). In 12 (33%) patients, there was EMG evidence of axonal
      damage with reinnervation, while in the other 24 (67%) patients, there was axonal
      damage without reinnervation. Only 18 (28%) patients had a good recovery. In
      conclusion, NI following IMI is a preventable iatrogenic hazard, which carries a
      poor prognosis.

PMID- 16787516
TI  - Steroid responsive small nerve fibre neuropathy: comment on article by Dabby et
      al.

PMID- 16787518
TI  - Clinical and electrophysiological evaluation of peripheral neuropathy in
      rheumatoid arthritis.

PMID- 16787519
TI  - Three-year inhibition of aldose reductase on development of symptomatic
      neuropathy in diabetic patients.

PMID- 16787520
TI  - A novel approach to the investigation of potential precipitating factors in type
      1 diabetes.

PMID- 16787521
TI  - Association between infectious diseases and type 1 diabetes: a case-crossover
      study.
AB  - BACKGROUND: To investigate the role of infectious diseases in the development of
      type 1 diabetes, this study estimated the relative risks of type 1 diabetes
      immediately after infectious diseases. RESEARCH DESIGN AND METHODS: A case
      crossover design was employed. Information on infectious diseases during 407 d
      before the onset of type 1 diabetes was collected from medical records and
      parents' interviews for 260 patients in Chinese type 1 diabetes registry. The
      frequency of infectious diseases in 42 d before the onset of type 1 diabetes was
      compared with either the usual frequency of infectious diseases over the past
      year or the actual frequency of infectious diseases in a comparable 42-d control
      period. RESULTS: Forty-eight (18%) patients were reported to have infectious
      diseases during this period based on medical records and interviews with parents.
      The relative risk of type 1 diabetes onset was markedly elevated to 10.1 (5.6,
      17.9) immediately after infectious diseases, suggesting the role of infections as
      a precipitator. The relative risk decreased gradually before and after 42 d and
      was similar between male and female patients. CONCLUSION: The results showed that
      infectious diseases are associated with a large and transient increase in the
      risk of type 1 diabetes during 42 d after the infection.

PMID- 16787522
TI  - Urinary cytokine response to asymptomatic bacteriuria in type 1 diabetic children
      and young adults.
AB  - It has been reported that urinary interleukin-6 (IL-6) and IL-8 levels are
      decreased in adult diabetic women with asymptomatic bacteriuria (ASB) when
      compared with non-diabetic women with ASB. Such impaired cytokine excretion might
      play a role in the higher prevalence of ASB among diabetic subjects. The aim of
      this study was to examine the urinary IL profile in children and young adults
      with type 1 diabetes mellitus (T1DM) with and without ASB. Midstream clean
      voiding urine samples were collected and cultured from 133 patients with T1DM
      (age: 15.6 +/- 5.7 yr) and 178 controls (14.1 +/- 4.7 yr) for two consecutive
      days. ASB was diagnosed in the case of >or=10(5) bacteria/mL. The urinary IL-6
      and IL-8 concentrations were determined, and the presence of leukocyturia was
      also recorded. The prevalence of ASB was 16.5% in diabetic subjects and 2.8% in
      controls (p = 0.001). There was no difference between the diabetic and the
      control groups in the prevalence of 'IL-6-uria' (21.9 vs. 18.0%; p = 0.41), but
      IL-8 was more frequently detectable in the diabetic group (47.4 vs. 27.5%; p =
      0.001). In individuals with ASB, the IL-8 level was similar in the diabetic
      (median: 70.0 pg/mg creatinine) and control group (42.3 pg/mg creatinine; p =
      0.8). Indeed, the IL-8 levels were higher in diabetic subjects with ASB as
      compared with those without it (70.0 vs. <3.1 pg/mg creatinine; p = 0.001), and
      there was a significant association between the urinary IL-8 concentration and
      the bacterial count (p = 0.001). Diabetic patients with leukocyturia had higher
      IL-8 concentration than those without it (20.9 vs. <3.1 pg/mg creatinine; p =
      0.003). Weak significant correlation was found between urinary IL-8 and
      hemoglobin A1c (HbA1c) (r = 0.4; p = 0.002). The sensitivity and specificity of
      leukocyturia were 50 and 89.9% in the whole population and those of IL-8 were
      74.1 and 67.5%, respectively. In diabetic patients, 36.4% of the bacteriuria were
      gram-negative and 63.6% gram-positive. Our results suggest that diabetic children
      with ASB mount an IL-8 response to pathogens, which is comparable to non-diabetic
      children with bacteriuria. Thus, early in the natural history of diabetes, there
      are no significant changes in the IL response of children with ASB, as previously
      reported in adults.

PMID- 16787523
TI  - Continuous subcutaneous glucose monitoring in children with type 1 diabetes
      mellitus: a single-blind, randomized, controlled trial.
AB  - BACKGROUND: Tight glycemic control delays the long-term complications of type 1
      diabetes mellitus (T1DM) but increases the risk for hypoglycemia. The continuous
      glucose-monitoring system (CGMS) provides blood glucose (BG) readings every 5
      min, and its accuracy and reliability has been established in adults. However,
      there are limited data on its efficacy and safety in children. The purpose of
      this study was to determine if CGMS use improves metabolic control in children
      with T1DM. METHODS: Twenty-seven children (12 male) with T1DM participated in
      this single-blind, randomized, controlled trial. Participants (age: 11.4 +/- 3.7
      (mean +/- SD) yr, range: 7-17 yr) were randomized to an intervention group (n =
      18) or a control group (n = 9). Both groups wore the CGMS for 72-h periods at 0,
      2, and 4 months. Adjustments in therapy for the intervention group were based on
      both CGMS and self-monitoring of BG (SMBG) data, while only SMBG data were used
      for the control group. Hemoglobin A1c (HbA1c) was determined at 0, 2, 4, and 6
      months. The change in HbA1c from 0 to 6 months (HbA1c(Delta1-4)) and mean daily
      area under the CGMS curve for glucose <70 mg/dL area under the curve (AUC(<70))
      were compared between groups. RESULTS: At study entry, HbA1c levels were similar
      in the intervention and control groups (8.4 +/- 0.98 and 8.8 +/- 0.86%,
      respectively; p = 0.12) but were significantly lower in the intervention group
      compared with the control group at study completion (7.8 +/- 0.88 and 8.6 +/-
      0.95%, respectively; p = 0.02). The decrease in HbA1c of 0.61 +/- 0.68% in the
      intervention group was statistically significant (p = 0.03), whereas the decrease
      in HbA1c of 0.28 +/- 0.78% in the control group was not. Nonetheless, the
      differences in HbA1c(Delta1-4) between groups did not reach statistical
      significance (p = 0.13). There was no statistically significant difference in
      AUC(<70) between study groups (p = 0.18). CONCLUSION: CGMS use may improve
      metabolic control in children with T1DM without increasing the risk for
      hypoglycemia.

PMID- 16787524
TI  - Prevalence and risk factors for microalbuminuria in a population-based sample of
      children and adolescents with T1DM in Western Australia.
AB  - OBJECTIVE: To define the prevalence and describe the natural history of
      microalbuminuria (MA) in a population-based sample of children with type 1
      diabetes mellitus (T1DM). METHODS: Children with T1DM diagnosed <or=16 yrs and
      screened for MA were identified through the Western Australia diabetes register.
      Three-monthly hemoglobin (HbA1c) was performed from diagnosis. MA screening
      (albumin excretion rate in three timed overnight samples) was performed yearly
      after 10 yrs of age or after 5 yrs from diagnosis. Cox proportional model
      assessed the risk of different variables on the occurrence of MA. Kaplan-Meier
      survival analyses (log-rank test) estimated the probability of developing MA.
      RESULTS: Nine hundred and fifty-five T1DM children (462 male), mean diabetes
      duration of 7.6 yrs and mean age at onset of diabetes of 8.5 yrs were selected
      for the study. MA, mean albumin excretion rate >or=20 and <200 microg/min,
      developed in 128 subjects (13.4%) at mean diabetes duration of 7.6 yrs.
      Cumulative probability for MA was 16% after 10 yrs. Determinants for MA were
      HbA1c [hazard ratio (HR) 1.21; 95% confidence interval (CI) 1.05-1.38; p =
      0.007], onset of puberty (HR 8.01; 95% CI 3.18-20.16; p < 0.001) and age at
      diagnosis (HR 1.25; 95% CI 1.18-1.33; p < 0.001). Females had a higher
      probability for MA during puberty than males (p = 0.03). The total incidence of
      MA (subjects with MA/100 person-years) was 1.26, 1.85 and 2.44 for those who
      developed diabetes at ages <5 yrs, 5-11 yrs and >11 yrs, respectively.
      CONCLUSIONS: Onset of puberty, diabetes duration and metabolic control are major
      factors predisposing the development of MA. Children diagnosed with T1DM at
      younger ages have a prolonged time for developing MA.

PMID- 16787525
TI  - The development of non-insulin-dependent diabetes after total body irradiation
      and bone marrow transplantation in adolescence: a case report and literature
      review.
AB  - A 6-yr-old-child received total body irradiation (TBI) and bone marrow
      transplantation (BMT) for relapsed acute lymphocytic leukemia. Nine years later,
      he developed diabetes mellitus (DM). He was started on basal bolus insulin
      therapy. Islet cell and anti-GAD antibodies were negative. Insulin and C-peptide
      levels were elevated consistent with insulin resistance (IR), even though his
      body mass index (BMI) was only 19.5. Hepatocyte nuclear factor (HNF-1alpha)
      mutation was not detected. Insulin was stopped and hemoglobin Alc (HbA1c)
      stabilized at 6.5% on gliclazide 40 mg/day. TBI has rarely been associated with
      IR and the development of diabetes. These patients can be managed with oral
      hypoglycemic agents and do not necessarily require insulin. Patients who received
      BMT and TBI may require long-term monitoring of glucose and lipid metabolism.

PMID- 16787527
TI  - Viruses take center stage in cellular evolution.
AB  - The origins of viruses are shrouded in mystery, but advances in genomics and the
      discovery of highly complex giant DNA viruses have stimulated new hypotheses that
      DNA viruses were involved in the emergence of the eukaryotic cell nucleus, and
      that they are worthy of being considered as living organisms.

PMID- 16787528
TI  - Variation in fiberoptic bead-based oligonucleotide microarrays: dispersion
      characteristics among hybridization and biological replicate samples.
AB  - BACKGROUND: Gene expression microarray technology continues to evolve and its use
      has expanded into all areas of biology. However, the high dimensionality of the
      data makes analysis a difficult challenge. Evaluating measurements and estimating
      the significance of the observed differences among samples remain important
      issues that must be addressed for each technology platform. In this work we use a
      consecutive sampling method to characterize the dispersion patterns of data
      generated from Illumina fiberoptic bead-based oligonucleotide arrays. RESULTS: To
      describe general properties of the dispersion we used a linear function SD = a +
      bY(mean), approximating the standard deviation across arrays (Y(mean) is the mean
      expression of a given consecutive sample). First we examined three levels of
      variability: 1) same cell culture, same reverse transcription, duplicate
      hybridizations; 2) same cell culture, reverse transcription replicates; 3)
      parallel cultures. Each higher level is expected to introduce a new source of
      variability. We observed minor differences in the constant term: the mean values
      are 3.5, 3.1 and 3.5, respectively. However, the mean coefficient b increased
      from 0.045 to 0.147 and 0.133. We compared the coefficients derived from the
      consecutive sampling to those obtained from the standard deviation of individual
      gene expressions and found them in good agreement. In the second experiment
      samples we detected 11 genes with systematically different expressions between
      the experiment samples treated with glucose oxidase and controls and corroborated
      the selection using the Mann-Whitney and other tests. We also compared the
      consecutive sampling and coincidence method to t-test: the average percentage of
      consistency was above 80 for the former and below 50 for the latter. CONCLUSION:
      Our results indicate that the consecutive sampling method and standard deviation
      function provide a convenient description of the overall dispersion of Illumina
      arrays. We observed that the constant term of the standard deviation function is
      at average approximately the same for duplicate hybridization as for the assays
      with additional sources of variability. Furthermore, among the genes affected by
      glucose oxidase treatment we identified 6 genes in oxidative stress pathways and
      5 genes involved in DNA repair. Finally, we noted that the consecutive sampling
      and coincidence test provide, under given conditions, more consistent results
      than the t-test. REVIEWERS: This article was reviewed by Alexander Karpikov
      (nominated by Mark Gerstein), Jordan King and Eugene V. Koonin.

PMID- 16787529
TI  - The normal human chondro-osseous junctional region: evidence for contact of
      uncalcified cartilage with subchondral bone and marrow spaces.
AB  - BACKGROUND: The chondro-osseous junctional region of diarthrodial joints is
      peculiarly complex and may be considered to consist of the deepest layer of non
      calcified cartilage, the tidemark, the layer of calcified cartilage, a thin
      cement line (between the calcified cartilage and the subchondral bone) and the
      subchondral bone. A detailed knowledge of the structure, function and
      pathophysiology of the normal chondro-osseous junction is essential for an
      understanding of the pathogenesis of osteoarthrosis. METHODS: Full thickness
      samples from human knee joints were processed and embedded in paraffin wax. One
      hundred serial sections (10 mum thick) were taken from the chondro-osseous
      junctional region of a block from the medial tibial plateau of a normal joint.
      They were stained with haematoxylin and eosin and photographed. For a simple
      physical reconstruction images of each 10th sequential tissue section were
      printed and the areas of the photomicrographs containing the chondro-osseous
      junctional region were cut out and then overlaid so as to create a three
      dimensional (3D) model of this region. A 3D reconstruction was also made using
      computer modelling. RESULTS: Histochemical staining revealed some instances where
      prolongations of uncalcified cartilage, delineated by the tidemark, dipped into
      the calcified cartilage and, in places, abutted onto subchondral bone and marrow
      spaces. Small areas of uncalcified cartilage containing chondrocytes (virtual
      islands) were seen, in two-dimensional (2D) sections, to be apparently entombed
      in calcified matrix. The simple physical 3D reconstruction confirmed that these
      prolongations of uncalcified cartilage were continuous with the cartilage of zone
      IV and demonstrated that the virtual islands of uncalcified cartilage were cross
      sections of these prolongations. The computer-generated 3D reconstructions
      clearly demonstrated that the uncalcified prolongations ran through the calcified
      cartilage to touch bone and marrow spaces and confirmed that the apparent
      entombment of chondrocytes was a 2D artefact. CONCLUSION: This study demonstrates
      that the chondro-osseous junctional region is more complex than previously
      described. The tidemark is a clearly defined boundary delineating uncalcified
      from calcified cartilage. It is not a straight line across a joint, but a complex
      three-dimensional structure that follows uncalcified cartilage prolongations
      dipping down through the calcified cartilage to abut onto subjacent bone or
      marrow spaces.

PMID- 16787530
TI  - Expression of caspase-3, p53 and Bcl-2 in generalized aggressive periodontitis.
AB  - BACKGROUND: Apoptosis, or programmed cell death is a form of physiological cell
      death. It is increased or decreased in the presence of infection, inflammation or
      tissue remodelling. Previous studies suggest that apoptosis is involved in the
      pathogenesis of inflammatory periodontal disease. The aim of the present study
      was to investigate the clinical features and known indicators of apoptosis (p53,
      Bcl-2, Caspase-3) in patients with generalized aggressive periodontitis (GAP)
      METHODS: Eight patients with GAP, who had sites with probing depths (PD) > 5 mm,
      and 10 periodontally-healthy persons were included in the study. Clinical
      examinations and PD were performed, and the plaque index and gingival index were
      recorded. Gingival tissues biopsies were obtained from active site of each
      patient and from healthy individuals. The expression of caspase-3, Bcl-2, and p53
      was evaluated by immunohistochemistry RESULTS: There were no significant
      differences between GAP and control group with respect to levels of caspase-3 and
      p53 expression (P > 0.05). Contrary, the frequency of grade 3 expression of Bcl-2
      was higher in GAP group than the control group. CONCLUSION: The higher frequency
      of Bcl-2 expression in GAP group indicates and delayed apoptosis can lead to
      increasing resident inflammatory cells in periodontal tissues and resulting in
      progressive periodontal destruction.

PMID- 16787531
TI  - Tissue-specific expression of TRP channel genes in the mouse and its variation in
      three different mouse strains.
AB  - BACKGROUND: The purpose of this work was to study the gene expression of
      transient receptor potential (TRP) channels in the mouse. The application of a
      standardized and quantitative technique, TaqMan RT-PCR, should give information
      about the pattern and relative importance of TRP channels for murine tissues and
      cell types. To verify data sets with an independent method, we studied the
      occurrence of some of the transcripts by in situ hybridization. RESULTS: We have
      characterized the mRNA expression of 22 TRP channels in the mouse with a focus on
      nerve and muscle tissues. This is the first study to describe the expression
      profiles of all channel isoforms of the four related Group 1 subfamilies (TRPC,
      TRPV, TRPM and TRPA) with a standardized and quantitative technique. Comparisons
      of transcript abundance showed a consistent dominance of TRPM7 and TRPC3 in most
      tissues. We further observed characteristic patterns and differences in gene
      expression of individual channels ranging over three orders of magnitude. The
      overall level of TRP channel mRNAs was highest in brain areas followed by kidney,
      lung, reproductive organs and muscle. In brain TRPM3 and TRPM7 dominated and 19
      other isoforms were detected. In lung and kidney TRPV4, TRPV5 and TRPM7 were
      found in highest levels. TRPM7, TRPC3, TRPC6 and TRPM3 mRNAs were
      characteristically present in all tested muscle tissues. Most data obtained with
      the C57Bl/10 mouse strain were confirmed with Balb/c and NOD mice. However,
      TRPC3, C6, TRPM7, M3, TRPV2 and V4 expression showed marked differences in the
      three tested mouse strains. In situ hybridization revealed co-expression of
      transcripts on the cellular level and widely confirmed the data obtained with RT
      PCR. CONCLUSION: Transcripts coding for members of the TRPC, TRPV, TRPM and TRPA
      subfamilies of TRP cation channels are present in a broad spectrum of murine
      tissues. Several channel isoforms often coexist in a specific tissue or cell
      type. TRP channel expression does not show typical tissue specific dominance of
      individual members as is known from other ion channel families. Mouse strain
      specific variations of TRP channel expression indicate that genetic background or
      physiological requirements considerably influence expression levels.

PMID- 16787533
TI  - The CAP cancer protocols--a case study of caCORE based data standards
      implementation to integrate with the Cancer Biomedical Informatics Grid.
AB  - BACKGROUND: The Cancer Biomedical Informatics Grid (caBIG) is a network of
      individuals and institutions, creating a world wide web of cancer research. An
      important aspect of this informatics effort is the development of consistent
      practices for data standards development, using a multi-tier approach that
      facilitates semantic interoperability of systems. The semantic tiers include (1)
      information models, (2) common data elements, and (3) controlled terminologies
      and ontologies. The College of American Pathologists (CAP) cancer protocols and
      checklists are an important reporting standard in pathology, for which no
      complete electronic data standard is currently available. METHODS: In this
      manuscript, we provide a case study of Cancer Common Ontologic Representation
      Environment (caCORE) data standard implementation of the CAP cancer protocols and
      checklists model--an existing and complex paper based standard. We illustrate the
      basic principles, goals and methodology for developing caBIG models. RESULTS:
      Using this example, we describe the process required to develop the model, the
      technologies and data standards on which the process and models are based, and
      the results of the modeling effort. We address difficulties we encountered and
      modifications to caCORE that will address these problems. In addition, we
      describe four ongoing development projects that will use the emerging CAP data
      standards to achieve integration of tissue banking and laboratory information
      systems. CONCLUSION: The CAP cancer checklists can be used as the basis for an
      electronic data standard in pathology using the caBIG semantic modeling
      methodology.

PMID- 16787532
TI  - IgE sensitisation in relation to flow-independent nitric oxide exchange
      parameters.
AB  - BACKGROUND: A positive association between IgE sensitisation and exhaled NO
      levels has been found in several studies, but there are no reports on the
      compartment of the lung that is responsible for the increase in exhaled NO levels
      seen in IgE-sensitised subjects. METHODS: The present study comprised 288 adult
      subjects from the European Community Respiratory Health Survey II who were
      investigated in terms of lung function, IgE sensitisation (sum of specific IgE),
      smoking history and presence of rhinitis and asthma. Mean airway tissue
      concentration of NO (CawNO), airway transfer factor for NO (DawNO), mean alveolar
      concentration of NO (CalvNO) and fractional exhaled concentration of NO at a flow
      rate of 50 mL s(-1) (FENO 0.05) were determined using the extended NO analysis.
      RESULTS: IgE-sensitised subjects had higher levels (geometric mean) of FENO 0.05
      (24.9 vs. 17.3 ppb) (p < 0.001), DawNO (10.5 vs. 8 mL s(-1)) (p = 0.02) and CawNO
      (124 vs. 107 ppb) (p < 0.001) and positive correlations were found between the
      sum of specific IgE and FENO 0.05, CawNO and DawNO levels (p < 0.001 for all
      correlations). Sensitisation to cat allergen was the major determinant of exhaled
      NO when adjusting for type of sensitisation. Rhinitis and asthma were not
      associated with the increase in exhaled NO variables after adjusting for the
      degree of IgE sensitisation. CONCLUSION: The presence of IgE sensitisation and
      the degree of allergic sensitisation were related to the increase in airway NO
      transfer factor and the increase in NO concentration in the airway wall.
      Sensitisation to cat allergen was related to the highest increases in exhaled NO
      parameters. Our data suggest that exhaled NO is more a specific marker of
      allergic inflammation than a marker of asthma or rhinitis.

PMID- 16787534
TI  - Quality of health information for cervical cancer treatment on the internet.
AB  - BACKGROUND: The internet has become a frequently used and powerful tool for
      patients seeking medical information. This information may not undergo the same
      quality consideration as the peer-review criteria for publication of information
      in a journal. The aim of this study is to assess the quality of internet sites
      providing information on the treatment of cervical cancer, with comparisons
      between the quality assessments made by an educated lay person and an expert in
      the field. METHODS: A search of the World Wide Web was made by a lay person to
      identify sites containing information on the treatment of cervical cancer. The
      credibility and accuracy of these sites was assessed using predefined criteria
      based on 'Criteria for Assessing the Quality of Health Information on the
      Internet' and accepted guidelines for the treatment of cervical cancer. The
      assessment was made independently and in duplicate by the lay reviewer and
      medical expert in order to allow comparison. RESULTS: 46 relevant websites were
      assessed. Only one site contained all the credibility and accuracy criteria, with
      a further website containing all the credibility criteria. The majority of sites,
      38/46, were deemed easy to navigate. The agreement between lay person and expert
      was good with only 6 items in total changed by the expert. CONCLUSION: This study
      clearly shows there is wide variation in quality of websites available to
      patients on the treatment of cervical cancer. Further research and consideration
      is needed on the effects of website information on gynaecological cancer patients
      and how steps can be made to insure the posting of good quality information.

PMID- 16787535
TI  - Identification of multiple integrin beta1 homologs in zebrafish (Danio rerio).
AB  - BACKGROUND: Integrins comprise a large family of alpha,beta heterodimeric,
      transmembrane cell adhesion receptors that mediate diverse essential biological
      functions. Higher vertebrates possess a single beta1 gene, and the beta1 subunit
      associates with a large number of alpha subunits to form the major class of
      extracellular matrix (ECM) receptors. Despite the fact that the zebrafish (Danio
      rerio) is a rapidly emerging model organism of choice for developmental biology
      and for models of human disease, little is currently known about beta1 integrin
      sequences and functions in this organism. RESULTS: Using RT-PCR, complete coding
      sequences of zebrafish beta1 paralogs were obtained from zebrafish embryos or
      adult tissues. The results show that zebrafish possess two beta1 paralogs (beta1
      1 and beta1-2) that have a high degree of identity to other vertebrate beta1
      subunits. In addition, a third, more divergent, beta1 paralog is present (beta1
      3), which may have altered ligand-binding properties. Zebrafish also have other
      divergent beta1-like transcripts, which are C-terminally truncated forms lacking
      the transmembrane and cytoplasmic domains. Together with beta1-3 these truncated
      forms comprise a novel group of beta1 paralogs, all of which have a mutation in
      the ADMIDAS cation-binding site. Phylogenetic and genomic analyses indicate that
      the duplication that gave rise to beta1-1 and beta1-2 occurred after the
      divergence of the tetrapod and fish lineages, while a subsequent duplication of
      the ancestor of beta1-2 may have given rise to beta1-3 and an ancestral truncated
      paralog. A very recent tandem duplication of the truncated beta1 paralogs appears
      to have taken place. The different zebrafish beta1 paralogs have varied patterns
      of temporal expression during development. Beta1-1 and beta1-2 are ubiquitously
      expressed in adult tissues, whereas the other beta1 paralogs generally show more
      restricted patterns of expression. CONCLUSION: Zebrafish have a large set of
      integrin beta1 paralogs. beta1-1 and beta1-2 may share the roles of the solitary
      beta1 subunit found in other vertebrates, whereas beta1-3 and the truncated beta1
      paralogs may have acquired novel functions.

PMID- 16787536
TI  - Targeted disruption of cubilin reveals essential developmental roles in the
      structure and function of endoderm and in somite formation.
AB  - BACKGROUND: Cubilin is a peripheral membrane protein that interacts with the
      integral membrane proteins megalin and amnionless to mediate ligand endocytosis
      by absorptive epithelia such as the extraembryonic visceral endoderm (VE).
      RESULTS: Here we report the effects of the genetic deletion of cubilin on mouse
      embryonic development. Cubilin gene deletion is homozygous embryonic lethal with
      death occurring between 7.5-13.5 days post coitum (dpc). Cubilin-deficient
      embryos display developmental retardation and do not advance morphologically
      beyond the gross appearance of wild-type 8-8.5 dpc embryos. While mesodermal
      structures such as the allantois and the heart are formed in cubilin mutants,
      other mesoderm-derived tissues are anomalous or absent. Yolk sac blood islands
      are formed in cubilin mutants but are unusually large, and the yolk sac blood
      vessels fail to undergo remodeling. Furthermore, somite formation does not occur
      in cubilin mutants. Morphological abnormalities of endoderm occur in cubilin
      mutants and include a stratified epithelium in place of the normally simple
      columnar VE epithelium and a stratified cuboidal epithelium in place of the
      normally simple squamous epithelium of the definitive endoderm. Cubilin-deficient
      VE is also functionally defective, unable to mediate uptake of maternally derived
      high-density lipoprotein (HDL). CONCLUSION: In summary, cubilin is required for
      embryonic development and is essential for the formation of somites, definitive
      endoderm and VE and for the absorptive function of VE including the process of
      maternal-embryo transport of HDL.

PMID- 16787539
TI  - Evidence for handheld electronic medical records in improving care: a systematic
      review.
AB  - BACKGROUND: Handheld electronic medical records are expected to improve physician
      performance and patient care. To confirm this, we performed a systematic review
      of the evidence assessing the effects of handheld electronic medical records on
      clinical care. METHODS: To conduct the systematic review, we searched MEDLINE,
      EMBASE, CINAHL, and the Cochrane library from 1966 through September 2005. We
      included randomized controlled trials that evaluated effects on practitioner
      performance or patient outcomes of handheld electronic medical records compared
      to either paper medical records or desktop electronic medical records. Two
      reviewers independently reviewed citations, assessed full text articles and
      abstracted data from the studies. RESULTS: Two studies met our inclusion
      criteria. No other randomized controlled studies or non-randomized controlled
      trials were found that met our inclusion criteria. Both studies were
      methodologically strong. The studies examined changes in documentation in
      orthopedic patients with handheld electronic medical records compared to paper
      charts, and both found an increase in documentation. Other effects noted with
      handheld electronic medical records were an increase in time to document and an
      increase in wrong or redundant diagnoses. CONCLUSION: Handheld electronic medical
      records may improve documentation, but as yet, the number of studies is small and
      the data is restricted to one group of patients and a small group of
      practitioners. Further study is required to determine the benefits with handheld
      electronic medical records especially in assessing clinical outcomes.

PMID- 16787537
TI  - Towards standardized measurement of adverse events in spine surgery: conceptual
      model and pilot evaluation.
AB  - BACKGROUND: Independent of efficacy, information on safety of surgical procedures
      is essential for informed choices. We seek to develop standardized methodology
      for describing the safety of spinal operations and apply these methods to study
      lumbar surgery. We present a conceptual model for evaluating the safety of spine
      surgery and describe development of tools to measure principal components of this
      model: (1) specifying outcome by explicit criteria for adverse event definition,
      mode of ascertainment, cause, severity, or preventability, and (2) quantitatively
      measuring predictors such as patient factors, comorbidity, severity of
      degenerative spine disease, and invasiveness of spine surgery. METHODS: We
      created operational definitions for 176 adverse occurrences and established
      multiple mechanisms for reporting them. We developed new methods to quantify the
      severity of adverse occurrences, degeneration of lumbar spine, and invasiveness
      of spinal procedures. Using kappa statistics and intra-class correlation
      coefficients, we assessed agreement for the following: four reviewers
      independently coding etiology, preventability, and severity for 141 adverse
      occurrences, two observers coding lumbar spine degenerative changes in 10
      selected cases, and two researchers coding invasiveness of surgery for 50 initial
      cases. RESULTS: During the first six months of prospective surveillance, rigorous
      daily medical record reviews identified 92.6% of the adverse occurrences we
      recorded, and voluntary reports by providers identified 38.5% (surgeons reported
      18.3%, inpatient rounding team reported 23.1%, and conferences discussed 6.1%).
      Trained observers had fair agreement in classifying etiology of 141 adverse
      occurrences into 18 categories (kappa = 0.35), but agreement was substantial
      (kappa > or = 0.61) for 4 specific categories: technical error, failure in
      communication, systems failure, and no error. Preventability assessment had
      moderate agreement (mean weighted kappa = 0.44). Adverse occurrence severity
      rating had fair agreement (mean weighted kappa = 0.33) when using a scale based
      on the JCAHO Sentinel Event Policy, but agreement was substantial for severity
      ratings on a new 11-point numerical severity scale (ICC = 0.74). There was
      excellent inter-rater agreement for a lumbar degenerative disease severity score
      (ICC = 0.98) and an index of surgery invasiveness (ICC = 0.99). CONCLUSION:
      Composite measures of disease severity and surgery invasiveness may allow
      development of risk-adjusted predictive models for adverse events in spine
      surgery. Standard measures of adverse events and risk adjustment may also
      facilitate post-marketing surveillance of spinal devices, effectiveness research,
      and quality improvement.

PMID- 16787538
TI  - Follicle-stimulating hormone (FSH) activates extracellular signal-regulated
      kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH
      receptor internalization.
AB  - BACKGROUND: The follicle-stimulating hormone receptor (FSH-R) is a seven
      transmembrane spanning receptor (7TMR) which plays a crucial role in male and
      female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular
      signal-regulated kinases (ERK). However, the mechanisms whereby the agonist
      stimulated FSH-R activates ERK are poorly understood. In order to activate ERK,
      some 7 TMRs require beta-arrestin-and dynamin-dependent internalization to occur,
      whereas some others do not. In the present study, we examined the ability of the
      FSH-activated FSH-R to induce ERK phosphorylation, in conditions where its beta
      arrestin- and dynamin-mediated internalization was impaired. METHODS: Human
      embryonic kidney (HEK) 293 cells were transiently transfected with the rat FSH-R.
      Internalization of the FSH-R was manipulated by co-expression of either a beta
      arrestin (319-418) dominant negative peptide, either an inactive dynamin K44A
      mutant or of wild-type beta-arrestin 1 or 2. The outcomes on the FSH-R
      internalization were assayed by measuring 125I-FSH binding at the cell surface
      when compared to internalized 125I-FSH binding. The resulting ERK phosphorylation
      level was visualized by Western blot analysis. RESULTS: In HEK 293 cells, FSH
      stimulated ERK phosphorylation in a dose-dependent manner. Co-transfection of the
      beta- arrestin (319-418) construct, or of the dynamin K44A mutant reduced FSH-R
      internalization in response to FSH, without affecting ERK phosphorylation.
      Likewise, overexpression of wild-type beta-arrestin 1 or 2 significantly
      increased the FSH-R internalization level in response to FSH, without altering
      FSH-induced ERK phosphorylation. CONCLUSION: From these results, we conclude that
      the FSH-R does not require beta-arrestin- nor dynamin-mediated internalization to
      initiate ERK phosphorylation in response to FSH.

PMID- 16787540
TI  - Oxidative stress and antioxidant defense in patients with chronic hepatitis C
      patients before and after pegylated interferon alfa-2b plus ribavirin therapy.
AB  - BACKGROUND: Oxidative stress could play a role in pathogenesis of hepatitis C
      virus (HCV) infection. The aim of our study is to determine oxidant/antioxidant
      status of patients with chronic hepatitis C (CHC), and the effect of pegylated
      interferon alfa-2b plus ribavirin combination therapy on oxidative stress.
      METHODS: Nineteen patients with chronic HCV infection and 28 healthy controls
      were included in the study. In control and patient groups, serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels, erythrocyte
      malondialdehyde (MDA) levels, erythrocyte CuZn-superoxide dismutase (SOD),
      erythrocyte glutathione peroxidase (GSH-Px) activities were measured. After
      pegylated interferon alfa-2b and ribavirin combination therapy for 48 weeks,
      these parameters were measured again in the patient group. RESULTS: Serum MDA
      levels increased significantly in CHC patients (n:19), before the treatment when
      compared with healthy subjects (n:28) 9.28 +/- 1.61, 4.20 +/- 1.47 nmol/ml, p <
      0.001 respectively. MDA concentration decreased significantly (p < 0.001) after
      the treatment as well as ALT, AST activity, in erythrocytes of these patients.
      Average antioxidant enzymes (superoxide dismutase and glutathione peroxidase)
      were significantly lower in erythrocytes of patients with CHC before treatment
      compared with the control group (both, p < 0.001). Chronic Hepatitis C patients
      after pegylated interferon alfa-2b and ribavirin therapy showed values of SOD,
      GSH-Px were significantly higher than pretreatment levels (both, p < 0.001).
      CONCLUSION: Our results show that patients with chronic HCV infection are under
      the influence of oxidative stress associated with lower levels of antioxidant
      enzymes. These impairments return to level of healthy controls after pegylated
      interferon alfa-2b plus ribavirin combination therapy of CHC patients. Although
      interferon and ribavirin are not antioxidants, their antiviral capacity might
      reduce viral load, and inflammation, and perhaps through this mechanism might
      reduce virus-induced oxidative stress.

PMID- 16787542
TI  - The contractile vacuole in Ca2+-regulation in Dictyostelium: its essential
      function for cAMP-induced Ca2+-influx.
AB  - BACKGROUND: cAMP-induced Ca2+-influx in Dictyostelium is controlled by at least
      two non-mitochondrial Ca2+-stores: acidic stores and the endoplasmic reticulum
      (ER). The acidic stores may comprise the contractile vacuole network (CV), the
      endosomal compartment and acidocalcisomes. Here the role of CV in respect to
      function as a potential Ca2+-store was investigated. RESULTS: Dajumin-GFP labeled
      contractile vacuoles were purified 7-fold by anti-GFP-antibodies in a magnetic
      field. The purified CV were shown for the first time to accumulate and release
      Ca2+. Release of Ca2+ was elicited by arachidonic acid or the calmodulin
      antagonist W7, the latter due to inhibition of the pump. The characteristics of
      Ca2+-transport and Ca2+-release of CV were compared to similarly purified
      vesicles of the ER labeled by calnexin-GFP. Since the CV proved to be a highly
      efficient Ca2+-compartment we wanted to know whether or not it takes part in cAMP
      induced Ca2+-influx. We made use of the LvsA--mutant expected to display reduced
      Ca2+-transport due to loss of calmodulin. We found a severe reduction of cAMP
      induced Ca2+-influx into whole cells. CONCLUSION: The contractile vacuoles in
      Dictyostelium represent a highly efficient acidic Ca2+-store that is required for
      cAMP-induced Ca2+-influx.

PMID- 16787543
TI  - Effects of equipment and technique on peak flow measurements.
AB  - BACKGROUND: Different lung function equipment and different respiratory
      manoeuvres may produce different Peak Expiratory Flow (PEF) results. Although the
      PEF is the most common lung function test, there have been few studies of these
      effects and no previous study has evaluated both factors in a single group of
      patients. METHODS: We studied 36 subjects (PEF range 80-570 l/min). All patients
      recorded PEF measurements using a short rapid expiration following maximal
      inspiration (PEF technique) or a forced maximal expiration to residual volume
      (FVC technique). Measurements were made using a Wright's peak flow meter, a
      turbine spirometer and a Fleisch pneumotachograph spirometer. RESULTS: The mean
      PEF was 8.7% higher when the PEF technique was used (compared with FVC technique,
      p < 0.0001). The mean PEF recorded with the turbine spirometer was 5.5% lower
      than the Wright meter reading. The Fleisch spirometer result was 19.5% lower than
      the Wright reading. However, adjustment of the Wrights measurements from the
      traditional Wright's scale to the new EU Peak Flow scale produced results that
      were only 7.2% higher than the Fleisch pneumotachograph measurements. CONCLUSION:
      Peak flow measurements are affected by the instruction given and by the device
      and Peak Flow scale used. Patient management decisions should not be based on PEF
      measurement made on different instruments.

PMID- 16787541
TI  - Insulin and glucose play a role in foam cell formation and function.
AB  - BACKGROUND: Foam cell formation in diabetic patients often occurs in the presence
      of high insulin and glucose levels. To test whether hyperinsulinemic
      hyperglycemic conditions affect foam cell differentiation, we examined gene
      expression, cytokine production, and Akt phosphorylation in human monocyte
      derived macrophages incubated with two types of oxidized low density lipoprotein
      (LDL), minimally modified LDL (mmLDL) and extensively oxidized LDL (OxLDL).
      METHODS AND RESULTS: Using Affymetrix GeneChip arrays, we found that several
      genes directly related to insulin signaling were changed. The insulin receptor
      and glucose-6-phosphate dehydrogenase were upregulated by mmLDL and OxLDL,
      whereas insulin-induced gene 1 was significantly down-regulated. In
      hyperinsulinemic hyperglycemic conditions, modified LDL upregulated Akt
      phosphorylation and expression of the insulin-regulated aminopeptidase. The level
      of proinflammatory cytokines, IL-lbeta, IL-12, and IL-6, and of a 5-lipoxygenase
      eicosanoid, 5-hydroxyeicosatetraenoic acid (5-HETE), was also increased.
      CONCLUSION: These results suggest that the exposure of macrophages to modified
      low density lipoproteins in hyperglycemic hyperinsulinemic conditions affects
      insulin signaling and promotes the release of proinflammatory stimuli, such as
      cytokines and eicosanoids. These in turn may contribute to the development of
      insulin resistance.

PMID- 16787544
TI  - Cancer mortality patterns in Ghana: a 10-year review of autopsies and hospital
      mortality.
AB  - BACKGROUND: Cancer mortality pattern in Ghana has not been reviewed since 1953,
      and there are no population-based data available for cancer morbidity and
      mortality patterns in Ghana due to the absence of a population-based cancer
      registry anywhere in the country. METHODS: A retrospective review of autopsy
      records of Department of Pathology, and medical certificate of cause of death
      books from all the wards of the Korle-Bu Teaching Hospital (KBTH), Accra, Ghana
      during the 10-year period 1991-2000 was done. RESULTS: The present study reviews
      3659 cancer deaths at the KBTH over the 10-year period. The male-to-female ratio
      was 1.2:1. The mean age for females was 46.5 [Standard Deviation (SD), 20.8]
      years, whilst that of males was 47.8 (SD, 22.2) years. The median age was 48
      years for females and 50 years for males. Both sexes showed a first peak in
      childhood, a drop in adolescence and young adulthood, and a second peak in the
      middle ages followed by a fall in the elderly, with the second peak occurring a
      decade earlier in females than in males. The commonest cause of cancer death in
      females was malignancies of the breast [Age-Standardized Cancer Ratio (ASCAR),
      17.24%], followed closely by haematopoietic organs (14.69%), liver (10.97%) and
      cervix (8.47%). Whilst in males, the highest mortality was from the liver
      (21.15%), followed by prostate (17.35%), haematopoietic organs (15.57%), and
      stomach (7.26%). CONCLUSION: Considering the little information available on
      cancer patterns in Ghana, this combined autopsy and death certification data from
      the largest tertiary hospital is of considerable value in providing reliable
      information on the cancer patterns in Ghana.

PMID- 16787546
TI  - Effects of work-related factors on the breastfeeding behavior of working mothers
      in a Taiwanese semiconductor manufacturer: a cross-sectional survey.
AB  - BACKGROUND: In recent years, the creation of supportive environments for
      encouraging mothers to breastfeed their children has emerged as a key health
      issue for women and children. The provision of lactation rooms and breast pumping
      breaks have helped mothers to continue breastfeeding after returning to work, but
      their effectiveness is uncertain. The aim of this study was to assess the effects
      of worksite breastfeeding-friendly policies and work-related factors on the
      behaviour of working mothers. METHODS: This study was conducted at a large
      Taiwanese semiconductor manufacturer in August-September 2003. Questionnaires
      were used to collect data on female employees' breastfeeding behaviour, child
      rearing and work status when raising their most recently born child. A total of
      998 valid questionnaires were collected, giving a response rate of 75.3%.
      RESULTS: The results showed that 66.9% of survey respondents breastfed initially
      during their maternity leave, which averaged 56 days. Despite the provision of
      lactation rooms and breast pumping breaks, only 10.6% mothers continued to
      breastfeed after returning to work, primarily office workers and those who were
      aware of their company's breastfeeding-friendly policies. CONCLUSION: In
      conclusion, breastfeeding-friendly policies can significantly affect
      breastfeeding behaviour. However, an unfavourable working environment, especially
      for fab workers, can make it difficult to implement breastfeeding measures. With
      health professionals emphasizing that the importance of breastfeeding for infant
      health, and as only females can perform lactation, it is vital that women's work
      "productive role" and family "reproductive role" be respected and accommodated by
      society.

PMID- 16787545
TI  - Surface display of proteins by gram-negative bacterial autotransporters.
AB  - Expressing proteins of interest as fusions to proteins of the bacterial envelope
      is a powerful technique with many biotechnological and medical applications.
      Autotransporters have recently emerged as a good tool for bacterial surface
      display. These proteins are composed of an N-terminal signal peptide, followed by
      a passenger domain and a translocator domain that mediates the outer membrane
      translocation of the passenger. The natural passenger domain of autotransporters
      can be replaced by heterologous proteins that become displayed at the bacterial
      surface by the translocator domain. The simplicity and versatility of this system
      has made it very attractive and it has been used to display functional enzymes,
      vaccine antigens as well as polypeptides libraries. The recent advances in the
      study of the translocation mechanism of autotransporters have raised several
      controversial issues with implications for their use as display systems. These
      issues include the requirement for the displayed polypeptides to remain in a
      translocation-competent state in the periplasm, the requirement for specific
      signal sequences and "autochaperone" domains, and the influence of the genetic
      background of the expression host strain. It is therefore important to better
      understand the mechanism of translocation of autotransporters in order to employ
      them to their full potential. This review will focus on the recent advances in
      the study of the translocation mechanism of autotransporters and describe
      practical considerations regarding their use for bacterial surface display.

PMID- 16787548
TI  - Powell's pearls: Edward Harry Bishop, MD (1913-1995).

PMID- 16787547
TI  - A steganalysis-based approach to comprehensive identification and
      characterization of functional regulatory elements.
AB  - The comprehensive identification of cis-regulatory elements on a genome scale is
      a challenging problem. We develop a novel, steganalysis-based approach for genome
      wide motif finding, called WordSpy, by viewing regulatory regions as a
      stegoscript with cis-elements embedded in 'background' sequences. We apply
      WordSpy to the promoters of cell-cycle-related genes of Saccharomyces cerevisiae
      and Arabidopsis thaliana, identifying all known cell-cycle motifs with high
      ranking. WordSpy can discover a complete set of cis-elements and facilitate the
      systematic study of regulatory networks.

PMID- 16787549
TI  - Managing ovarian masses during pregnancy.
AB  - The management of adnexal masses during pregnancy can be challenging for the
      patient and the clinician. The specter of a possible malignancy can sway the
      decision for intervention versus expectant management. The etiologies of ovarian
      masses are reflective of the patient's age; and, therefore, benign entities such
      as functional ovarian cysts, benign cystic teratomas, and serous cystadenomas
      predominate. In the unusual cases when cancer is present, they are typically germ
      cell and borderline ovarian tumors, and are commonly low stage and low grade.
      Ultrasound is the primary modality used to detect ovarian masses and to assess
      the risk of malignancy. Morphologic criteria more accurately identify benign
      cysts compared with malignant tumors. Tumor markers are used primarily to monitor
      disease status after treatment rather than establish the ovarian tumor diagnosis
      as a result of lack of specificity, because several markers can be elevated
      inherent to the pregnancy itself (eg, CA-125, beta-hCG). Expectant management is
      recommended for most pregnant patients with asymptomatic, nonsuspicious cystic
      ovarian masses. Surgical intervention during pregnancy is indicated for large
      and/or symptomatic tumors and those that appear highly suspicious for malignancy
      on imaging tests. The extent of surgery depends on the intraoperative diagnosis
      of a benign versus a malignant tumor. Conservative surgery is appropriate for
      benign masses and borderline ovarian tumors. More aggressive surgery is indicated
      for ovarian malignancies, including surgical staging. Although rarely necessary,
      chemotherapy has been used during pregnancy with minimal fetal toxicity in
      patients with advanced-stage ovarian cancer in which the risk of maternal
      mortality outweighs the fetal consequences.

PMID- 16787550
TI  - Late postpartum eclampsia: examples and review.
AB  - Eclampsia, defined as the occurrence of seizures in pregnant women, usually in
      the setting of preeclampsia and in the absence of other neurologic disorders,
      occurs mainly before, during , or within 48 hours after delivery. When
      convulsions occur later postpartum, diagnosis is difficult and treatment
      disputed. We review the entity of late postpartum eclampsia and report 2 examples
      in which the serum levels of antiangiogenic and angiogenic proteins were
      measured.

PMID- 16787551
TI  - Clinical proteomics: a novel diagnostic tool for the new biology of preterm
      labor, part I: proteomics tools.
AB  - The molecular mechanisms regulating myometrial contractility and preterm
      premature rupture of the membranes leading to preterm birth are poorly
      understood. The completion of the human genome sequence led to the development of
      functional genomics and gene array technology to simultaneously identify
      candidate genes potentially involved in regulation of human parturition. However,
      the study of living systems can now be expanded past genomics based on the
      rationale that it is the protein products of the genes, not simply gene
      expression, that have effects and cause disturbances at the cellular level.
      Therefore, identification of disease biomarkers, followed by a description of
      their functional networks, has the potential to significantly aid the development
      of new strategies for the prediction, diagnosis, and prevention of preterm birth.
      Interest in mass spectrometry and its use as a new clinical diagnostic tool has
      grown rapidly and is poised to become an important medical field for the next
      century.

PMID- 16787552
TI  - Alopecia areata: pathogenesis and potential for therapy.
AB  - Although the complete picture for alopecia areata (AA) pathogenesis has yet to be
      determined, recent research has made much progress in our understanding of the
      disease mechanism. Numerous circumstantial evidence supports the notion that AA
      is fundamentally a disease mediated by inflammatory cells and may be autoimmune
      in nature. Recent research has shown the hair-loss phenotype is precipitated
      predominantly by CD8+ lymphocytes, but the disease mechanism is driven by CD4+
      lymphocytes. Although genetic susceptibility is a key contributor to disease
      development, disease onset and phenotypic presentation are probably modified by
      complex environmental interplay. On the basis of our current understanding of AA
      disease pathogenesis, several experimental and theoretical therapeutic approaches
      might be possible. However, the pathogenetic disease mechanism is particularly
      robust and the development of a cure for AA will be a significant challenge.

PMID- 16787553
TI  - Cognitive therapy in relapse prevention in depression.
AB  - This paper reviews recent advances in application of cognitive therapy (CBT) to a
      therapeutic problem in depression. Modern follow-up studies indicate that, in
      spite of the efficacy of pharmacotherapy, relapse and recurrence rates in some
      depressed patients remain high. This does not appear mainly due to failure to
      receive medication, but to reflect intractability of the disorder. In acute
      treatment, psychological treatments, although beneficial, are less cost-effective
      than antidepressants, due to high costs of therapists. Benefit which lasts
      longer, particularly if combined with medication, may therefore be particularly
      valuable. There have now been seven randomized controlled trials of cognitive
      therapy designed specifically to test relapse and recurrence prevention. All have
      shown significant benefit, which lasts beyond the cessation of therapy. The
      effect appears to be more on preventing symptom return than on lessening current
      symptoms, to summate well with continuation and maintenance antidepressant, and
      not to be due simply to enhanced medication adherence. Incorporation into routine
      clinical practice is now appropriate and recommendations are proposed.

PMID- 16787554
TI  - A meta-analysis of relapse rates with adjunctive psychological therapies compared
      to usual psychiatric treatment for bipolar disorders.
AB  - This paper reviews published randomized controlled treatment trials of
      psychological therapies added to standard psychiatric treatment vs. standard
      psychiatric treatment alone to explore whether adjunctive psychotherapy reduces
      relapse rates in individuals with bipolar disorders. Core components and
      characteristics of effective psychological therapies were identified from
      descriptions in the literature. Relapse rates were calculated for selected
      treatment trials and then pooled odds ratios were calculated using meta
      analytical techniques that explored differences in outcome according to therapy
      model, type of relapse experienced and whether the subject was euthymic at entry
      to the study. The different therapy models have a number of similar components. A
      meta-analysis of eight recent studies demonstrates a significant reduction in
      relapse rates (of about 40%) compared to standard treatment alone. Therapies were
      most effective in preventing relapses in subjects who were euthymic when
      recruited into the treatment trial, and may be less effective in those with a
      high number of previous episodes (previous relapses >12). Efficacy studies
      demonstrate that adjunctive psychological treatments for individuals with bipolar
      disorders reduce relapse risk, but there is a need to undertake pragmatic
      effectiveness studies to determine which individuals with bipolar disorders are
      most likely to benefit from such interventions.

PMID- 16787555
TI  - What is the place of psychological treatments in mood disorders?
AB  - While psychotherapy has many applications for mood disorders, this paper focuses
      on those psychotherapies (cognitive behaviour therapy or CBT, and interpersonal
      psychotherapy or IPT) that have been manualized, extensively evaluated, and
      positioned as definitive therapies for unipolar depressive disorders. This paper
      suggests some reasons as to why their role and utility remain unclear. First,
      despite many randomized controlled efficacy studies, differentiation from other
      psychotherapies or control interventions appears to occur only when the actual
      control treatment possesses few therapeutic ingredients. Second, their testing as
      if they have universal application for non-specific diagnostic entities (e.g.
      major depression), in trials where there is a high rate of non-specific
      responsivity to intervention, has limited our capacity to identify the
      circumstances in which such treatments have specific benefits. Thus, many of the
      limitations to the knowledge base more reflect limitations reflecting the current
      evaluation of all antidepressant therapies rather than being unique to the
      psychotherapies. This paper argues for a change in the paradigms for evaluating
      the psychotherapies, and argues for a 'horses for courses' approach for
      conceptualizing the roles of the psychotherapies in managing mood disorders,
      rather than any model assuming their universal application.

PMID- 16787556
TI  - Recent non-medication trials of interpersonal psychotherapy for depression.
AB  - Interpersonal psychotherapy (IPT) is a time-limited treatment described in a
      manual and tested in numerous clinical trials, with and without medication. Four
      recent clinical trials are reviewed in situations where medication as a first
      line treatment for depression was not feasible (pregnancy, post partum,
      adolescence and in a developing country). The results show the efficacy of 12-16
      wk of IPT compared to treatment as usual or no treatment in reducing depressive
      symptoms. The therapists providing the treatment included psychiatrists,
      psychologists, social workers as well as non-mental-health workers. We do not
      know if these patients might have done even better with medication, but each
      study showed a significant remission of symptoms of patients in IPT compared to
      controls. The use of efficacious, time-limited psychotherapy, which can be
      administered by non-medical personnel can be economical. An obstacle to providing
      evidence-based psychotherapies is the paucity of practitioners trained in them.
      Until the gap between training in psychotherapy and the research evidence in
      psychotherapy is bridged in training programmes, it will be difficult to provide
      patients with these treatments.

PMID- 16787558
TI  - Calcium signaling in physiology and pathophysiology.
AB  - Calcium ions are the most ubiquitous and pluripotent cellular signaling molecules
      that control a wide variety of cellular processes. The calcium signaling system
      is represented by a relatively limited number of highly conserved transporters
      and channels, which execute Ca2+ movements across biological membranes and by
      many thousands of Ca2+-sensitive effectors. Molecular cascades, responsible for
      the generation of calcium signals, are tightly controlled by Ca2+ ions themselves
      and by genetic factors, which tune the expression of different Ca2+-handling
      molecules according to adaptational requirements. Ca2+ ions determine normal
      physiological reactions and the development of many pathological processes.

PMID- 16787559
TI  - Glial calcium signaling in physiology and pathophysiology.
AB  - Neuronal-glial circuits underlie integrative processes in the nervous system.
      Function of glial syncytium is, to a very large extent, regulated by the
      intracellular calcium signaling system. Glial calcium signals are triggered by
      activation of multiple receptors, expressed in glial membrane, which regulate
      both Ca2+ entry and Ca2+ release from the endoplasmic reticulum. The endoplasmic
      reticulum also endows glial cells with intracellular excitable media, which is
      able to produce and maintain long-ranging signaling in a form of propagating Ca2+
      waves. In pathological conditions, calcium signals regulate glial response to
      injury, which might have both protective and detrimental effects on the nervous
      tissue.

PMID- 16787560
TI  - Ca2+ signaling during vertebrate somitogenesis.
AB  - A variety of Ca2+ signals, in the form of intercellular pulses and waves, have
      been reported to be associated with the various sequential stages of
      somitogenesis: from convergent extension and the formation of the paraxial
      mesoderm; during the patterning of the paraxial mesoderm to establish segmental
      units; throughout the formation of the morphological boundaries that delineate
      the segmental units, and finally from within the maturing somites as they undergo
      subsequent development and differentiation. Due to both the technical challenges
      presented in imaging intact, developing embryos, and the subtle nature of the
      Ca2+ transients generated, they have proved to be difficult to visualize.
      However, a combination of cultured cell preparations and improvements in explant
      and whole embryo imaging techniques has begun to reveal a new and exciting class
      of developmental Ca2+ signals. In this chapter, we review the small, but
      expanding, number of reports in the literature and attempt to identify common
      characteristics of the somitogenic Ca2+ transients, such as their mode of
      generation, as well as their spatial and temporal features. This may help to
      elucidate the significance and function of these intriguing Ca2+ transients and
      thus integrate them into the complex signaling networks that orchestrate early
      developmental events.

PMID- 16787561
TI  - Ca2+ sparks as a plastic signal for skeletal muscle health, aging, and dystrophy.
AB  - Ca2+ sparks are the elementary units of intracellular Ca2+ signaling in striated
      muscle cells revealed as localized Ca2+ release events from sarcoplasmic
      reticulum (SR) by confocal microscopy. While Ca2+ sparks are well defined in
      cardiac muscle, there has been a general belief that these localized Ca2+ release
      events are rare in intact adult mammalian skeletal muscle. Several laboratories
      determined that Ca2+ sparks in mammalian skeletal muscle could only be observed
      in large numbers when the sarcolemmal membranes are permeabilized or the SR Ca2+
      content is artificially manipulated, thus the cellular and molecular mechanisms
      underlying the regulation of Ca2+ sparks in skeletal muscle remain largely
      unexplored. Recently, we discovered that membrane deformation generated by
      osmotic stress induced a robust Ca2+ spark response confined in close spatial
      proximity to the sarcolemmal membrane in intact mouse muscle fibers. In addition
      to Ca2+ sparks, prolonged Ca2+ transients, termed Ca2+ bursts, are also
      identified in intact skeletal muscle. These induced Ca2+ release events are
      reversible and repeatable, revealing a plastic nature in young muscle fibers. In
      contrast, induced Ca2+ sparks in aged muscle are transient and cannot be re
      stimulated. Dystrophic muscle fibers display uncontrolled Ca2+ sparks, where
      osmotic stress-induced Ca2+ sparks are not reversible and they are no longer
      spatially restricted to the sarcolemmal membrane. An understanding of the
      mechanisms that underlie generation of osmotic stress-induced Ca2+ sparks in
      skeletal muscle, and how these mechanisms are altered in pathology, will
      contribute to our understanding of the regulation of Ca2+ homeostasis in muscle
      physiology and pathophysiology.

PMID- 16787562
TI  - Molecular basis of inherited calcium channelopathies: role of mutations in pore
      forming subunits.
AB  - The pore-forming alpha subunits of voltage-gated calcium channels contain the
      essential biophysical machinery that underlies calcium influx in response to cell
      depolarization. In combination with requisite auxiliary subunits, these pore
      subunits form calcium channel complexes that are pivotal to the physiology and
      pharmacology of diverse cells ranging from sperm to neurons. Not surprisingly,
      mutations in the pore subunits generate diverse pathologies, termed
      channelopathies, that range from failures in excitation-contraction coupling to
      night blindness. Over the last decade, major insights into the mechanisms of
      pathogenesis have been derived from animals showing spontaneous or induced
      mutations. In parallel, there has been considerable growth in our understanding
      of the workings of voltage-gated ion channels from a structure-function,
      regulation and cell biology perspective. Here we document our current
      understanding of the mutations underlying channelopathies involving the voltage
      gated calcium channel alpha subunits in humans and other species.

PMID- 16787563
TI  - Store-operated calcium channels and pro-inflammatory signals.
AB  - In non-excitable cells such as T lymphocytes, hepatocytes, mast cells, endothelia
      and epithelia, the major pathway for calcium [Ca2+] entry is through store
      operated Ca2+ channels in the plasma membrane. These channels are activated by
      the emptying of intracellular Ca2+ stores, however, neither the gating mechanism
      nor the downstream targets of these channels has been clear established. Here, I
      review some of the proposed gating mechanisms of store-operated Ca2+ channels and
      the functional implications in regulating pro-inflammatory signals.

PMID- 16787564
TI  - Cross-talk between calcium and reactive oxygen species signaling.
AB  - Calcium [Ca2+] and reactive oxygen species (ROS) constitute the most important
      intracellular signaling molecules participating in the regulation and integration
      of diverse cellular functions. Here we briefly review cross-talk between the two
      prominent signaling systems that finely tune the homeostasis and integrate
      functionality of Ca2+ and ROS in different types of cells. Ca2+ modulates ROS
      homeostasis by regulating ROS generation and annihilation mechanisms in both the
      mitochondria and the cytosol. Reciprocal redox regulation of Ca2+ homeostasis
      occurs in different physiological and pathological processes, by modulating
      components of the Ca2+ signaling toolkit and altering characteristics of local
      and global Ca2+ signals. Functionally, interactions between Ca2+ and ROS
      signaling systems can be both stimulatory and inhibitory, depending on the type
      of target proteins, the ROS species, the dose, duration of exposure, and the cell
      contexts. Such extensive and complex cross-talk might enhance signaling
      coordination and integration, whereas abnormalities in either system might
      propagate into the other system and undermine the stability of both systems.

PMID- 16787565
TI  - Multiple mechanisms involved in oxytocin-induced modulation of myometrial
      contractility.
AB  - Oxytocin is a small peptide hormone with multiple sites of action in human body.
      It regulates a large number of reproduction-related processes in all species.
      Particularly important is its ability to stimulate uterine contractility. This is
      achieved by multiple mechanisms involving sarcoplasmic reticulum Ca2+ release and
      sensitization of the contractile apparatus to Ca2+. In this paper, we review the
      data published by us and other groups on oxytocin-induced modulation of uterine
      contractility. We conclude that sensitization of contractile apparatus to Ca2+ is
      the most relevant physiological effect of oxytocin on human myometrium.

PMID- 16787566
TI  - Regulation of TRP-like muscarinic cation current in gastrointestinal smooth
      muscle with special reference to PLC/InsP3/Ca2+ system.
AB  - Acetylcholine, the main enteric excitatory neuromuscular transmitter, evokes
      membrane depolarization and contraction of gastrointestinal smooth muscle cells
      by activating G protein-coupled muscarinic receptors. Although the cholinergic
      excitation is generally underlined by the multiplicity of ion channel effects,
      the primary event appears to be the opening of cation-selective channels; among
      them the 60 pS channel has been recently identified as the main target for the
      acetylcholine action in gastrointestinal myocytes. The evoked cation current,
      termed mI(CAT), causes either an oscillatory or a more sustained membrane
      depolarization response, which in turn leads to increases of the open probability
      of voltage-gated Ca2+ channels, thus providing Ca2+ entry in parallel with Ca2+
      release for intracellular Ca2+ concentration rise and contraction. In recent
      years there have been several significant developments in our understanding of
      the signaling processes underlying mICAT generation. They have revealed important
      synergistic interactions between M2 and M3 receptor subtypes, single channel
      mechanisms, and the involvement of TRPC-encoded proteins as essential components
      of native muscarinic cation channels. This review summarizes these recent
      findings and in particular discusses the roles of the phospholipase
      C/InsP3/intracellular Ca2+ release system in the mI(CAT) physiological
      regulation.

PMID- 16787567
TI  - Cytosolic calcium oscillations in submandibular gland cells.
AB  - Calcium oscillations can, by default, encode diverse and specific signals by
      different modes of modulation. Frequency modulation is illustrated by the
      activation of calcium/calmodulin-dependent protein kinase II at unit Hz, and of
      calcineurin at 10 mHz frequencies, respectively. The submandibular gland
      secretory axis is characterized by both potassium and osmolarity gradients from
      the luminal side of the secretory cells. Such gradients may play significant
      physiological roles through the feedback modulation of cholinergic stimulation.
      High potassium transforms plateau calcium increases induced by cholinergic
      stimulation of the submandibular acinar cells into oscillatory calcium increases.
      The ductal cells may have similar mechanisms of feedback modulation both by high
      potassium and by hypoosmolarity. Such feedback mechanisms could modulate the
      decision-making process for determining which secretory products are selectively
      released after nerve stimulation.

PMID- 16787568
TI  - Ca2+ sparks and Ca2+ glows in superior cervical ganglion neurons.
AB  - AIM: Ca2+ release from the endoplasmic reticulum (ER) is an integral component of
      neuronal Ca2+ signaling. The present study is to investigate properties of local
      Ca2+ release events in superior cervical ganglion (SCG) neurons. METHODS: Primary
      cultured SCG neurons were prepared from neonatal rats (P3-P7). Low concentration
      of caffeine was used to induce Ca2+ release from the ER Ca2+ store, and
      intracellular Ca2+ was recorded by high-resolution line scan confocal imaging and
      the Ca2+ indicator Fluo-4. RESULTS: Two populations of local Ca2+ release events
      with distinct temporal characteristics were evoked by 1.5 mmol/L caffeine near
      the surface membrane in the soma and the neurites of SCG neurons. Brief events
      similar to classic Ca2+ sparks lasted a few hundreds of milliseconds, whereas
      long-lasting events displayed duration up to tens of seconds. Typical somatic and
      neurite sparks were of 0.3- and 0.52-fold increase in local Fluo-4 fluorescence,
      respectively. Typical Ca2+ glows were brighter (deltaF/F0 approximately 0.6), but
      were highly confined in space. The half maximum of full duration of neurite
      sparks was much longer than those in the soma (685 vs 381 ms). CONCLUSION: Co
      existence of Ca2+ sparks and Ca2+ glows in SCG neurons indicates distinctive
      local regulation of Ca2+ release kinetics. The local Ca2+ signals of variable,
      site-specific temporal length may bear important implications in encoding a
      'memory' of the trigger signal.

PMID- 16787569
TI  - S-Nitrosoglutathione and glutathione act as NMDA receptor agonists in cultured
      hippocampal neurons.
AB  - AIM: To characterize the effect of combined pre- and postnatal morphine exposure
      on N-methyl-D-aspartate receptor (NMDA) receptor signaling in hippocampal neurons
      of the offspring of morphine-addicted female rats. METHODS: Cultured hippocampal
      neurons and synaptosomes were prepared from neonatal and 2-week-old offspring,
      respectively, of control or morphine-addicted female rats. The increase in the
      cytosolic Ca2+ concentration ([Ca2+]i) of cultured cells was measured using Fura
      2, and glutamate release from synaptosomes was measured enzymatically. RESULTS:
      Both glutamate and NMDA caused a dose-dependent increase in the [Ca2+]i. The
      nitric oxide (NO) donor, S-nitrosoglutathione (GSNO), but not 3
      morpholinosydnonimine, sodium nitroprusside, and S-nitroso-N-acetylpenicillamine,
      also induced a [Ca2+]i increase. GSNO and glutathione caused a dose-dependent
      increase in the [Ca2+]i with respective EC50 values of 56 and 414 micromol/L.
      Both effects were inhibited by Mg2+ or an NMDA receptor antagonist and were
      unaffected by the presence of a glutamate scavenger. The other glutathione
      derivatives, oxidized glutathione, S-methylglutathione, S-ethylglutathione, S
      propylglutathione, and S-butylglutathione, the dipeptides, Glu-Cys and Cys-Gly,
      and the antioxidants, dithiothreitol and mercaptoethanol, failed to induce a
      [Ca2+]i increase. In addition, glutathione caused a dose-dependent increase in
      glutamate release from synaptosomes. The maximal responses and the EC50 values
      for the glutamate-, NMDA-, GSNO-, and glutathione-induced [Ca2+]i increases and
      the glutathione-induced glutamate release were indistinguishable in the neurons
      of the offspring from control and morphine-addicted female rats. CONCLUSION: GSNO
      and glutathione act as NMDA receptor agonists and, in contrast to hippocampal
      brain slice, combined pre- and postnatal morphine exposure does not modulate NMDA
      receptor signaling in the cultured hippocampal neurons.

PMID- 16787570
TI  - Cellular mechanism for spontaneous calcium oscillations in astrocytes.
AB  - AIM: To determine the Ca2+ source and cellular mechanisms of spontaneous Ca2+
      oscillations in hippocampal astrocytes. METHODS: The cultured cells were loaded
      with Fluo-4 AM, the indicator of intracellular Ca2+, and the dynamic Ca2+
      transients were visualized with confocal laser-scanning microscopy. RESULTS: The
      spontaneous Ca2+ oscillations in astrocytes were observed first in co-cultured
      hippocampal neurons and astrocytes. These oscillations were not affected by
      tetrodotoxin (TTX) treatment and kept up in purity cultured astrocytes. The
      spontaneous Ca2+ oscillations were not impacted after blocking the voltage-gated
      Ca2+ channels or ethylenediamine tetraacetic acid (EDTA) bathing, indicating that
      intracellular Ca2+ elevation was not the result of extracellular Ca2+ influx.
      Furthermore, the correlation between the spontaneous Ca2+ oscillations and the
      Ca2+ store in endoplasmic reticulum (ER) were investigated with pharmacological
      experiments. The oscillations were: 1) enhanced when cells were exposed to both
      low Na+ (70 mmol/L) and high Ca2+ (5 mmol/L) solution, and eliminated completely
      by 2 micromol/L thapsigargin, a blocker of sarcoplasmic reticulum Ca2+-ATPase;
      and 2) still robust after the application with either 50 micromol/L ryanodine or
      400 micromol/L tetracaine, two specific antagonists of ryanodine receptors, but
      depressed in a dose-dependent manner by 2-APB, an InsP3 receptors (InsP3R)
      blocker. CONCLUSION: InsP3R-induced ER Ca2+ release is an important cellular
      mechanism for the initiation of spontaneous Ca2+ oscillation in hippocampal
      astrocytes.

PMID- 16787571
TI  - MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations
      in cultured hippocampal networks.
AB  - AIM: To investigate the changes in synchronized spontaneous Ca2+ oscillations
      induced by mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 at
      different concentrations in cultured hippocampal network. METHODS: Hippocampal
      neurons in culture for 1-2 weeks were used for this study. Spontaneous synaptic
      activities of these hippocampal neurons were examined by Ca2+ imaging using
      calcium-sensitive dye. MEK inhibitor PD98059 (10, 30, and 60 micromol/L) and
      SB202474 (10 and 60 micromol/L), a negative control for mitogen-activated protein
      kinase (MAPK) cascade study, were applied to the cells under the microscope while
      imaging was taking place. RESULTS: PD98059 at a lower concentration of 10
      micromol/L had little effect on the Ca2+ oscillation. At the higher concentration
      of 30 micromol/L, 5 min after application of PD98059, the spike frequency was
      decreased to 25.38% +/-7.40% (mean+/-SEM, n=16, P<0.01 vs medium control) of that
      of the control period. At an even higher concentration of 60 micromol/L, 5 min
      after application of PD98059, the spike frequency was decreased to 14.53%+/-5.34%
      (mean+/-SEM, n=16, P< 0.01 vs medium control) of that of the control period. The
      spike amplitude underwent a corresponding decrease. However, the negative control
      SB202474 at concentrations of 10 and 60 micromol/L had little inhibition effect
      on the Ca2+ oscillation. CONCLUSION: These results indicate that PD98059 inhibits
      synchronized spontaneous Ca2+ oscillation through inhibition of MEK, which hints
      that the MAPK cascade is required to maintain synchronized spontaneous Ca2+
      oscillation.

PMID- 16787572
TI  - Effect of osmotic stress on spontaneous calcium sparks in rat ventricular
      myocytes.
AB  - AIM: To study whether the volume of cardiomyocytes and their functions would
      change under severe pathological conditions or osmotic stress. To clarify the
      role of ryanodine receptors/calcium release channels (RyRs) in the functional
      change, the effect of osmotic stress on spontaneous Ca2+ sparks in rat
      ventricular myocytes was investigated. METHODS: A laser scanning confocal
      microscope was used to detect spontaneous Ca2+ sparks of intact or saponin
      permeabilized myocytes loaded with Fluo-4. High and low tonicity was obtained by
      adding sucrose and reducing NaCl concentration in the external medium,
      respectively. RESULTS: In intact myocytes the frequency of Ca2+ sparks was
      increased and decreased by hyperosmotic (1.5 T) and hyposmotic (0.6 T) exposure,
      respectively. In addition, hyperosmotic exposure increased the temporal
      parameters and decreased the spatial parameter of Ca2+ sparks, while opposite
      changes occurred with hyposmotic exposure. The spatio-temporal properties of Ca2+
      sparks were slightly affected by altering [K+]i (50-200 mmol/L) in saponin
      permeabilized myocytes in the presence of 8% dextran. It was observed that the
      spatio-temporal parameters of the Ca2+ sparks in permeabilized myocytes were dose
      dependently altered by dextran. The propagating velocity of Ca2+ waves in intact
      and permeabilized myocyte was also affected by osmotic pressure or dextran.
      CONCLUSION: The effect of osmotic stress on the frequency of spontaneous Ca2+
      sparks might be ascribed to the change of myoplasmic Ca2+ and Ca2+ content in the
      sarcoplasmic reticulum, while the effect on the spatio-temporal properties is
      caused by the alteration of Ca2+ diffusion mainly resulting from the
      morphological change of the myocytes.

PMID- 16787573
TI  - Molecular nature of sulfhydryl modification by hydrogen peroxide on type 1
      ryanodine receptor.
AB  - AIM: To elucidate the molecular nature of sulfhydryl modification by hydrogen
      peroxide on type 1 ryanodine receptor (RyR1). METHODS: Rabbit skeletal muscle
      sarcoplasmic reticulum was treated with hydrogen peroxide, then RyR1 complex was
      isolated. The proteins in the complex were analysed by electrophoresis, Western
      blot and electron microscopy. RESULTS: (1) Hydrogen peroxide induces inter
      subunit cross-linking within the tetrameric RyR1 molecule; (2) in parallel to
      inter-subunit cross-linking, the RyR1 molecule changes morphology; (3) the
      chemical and morphological changes are reversible: upon reduction by reducing
      agents, the RyR1 molecule regains its original state. CONCLUSION: These findings
      suggest that the molecular mechanism of RyR1 channel activity in sarcoplasmic
      reticulum regulated by hydrogen peroxide is through inter-subunit cross-linking
      within the tetrameric RyR1 molecule, which in turn induces structural changes of
      RyR1.

PMID- 16787574
TI  - Role of inositol 1,4,5-trisphosphate receptors in alpha1-adrenergic receptor
      induced cardiomyocyte hypertrophy.
AB  - AIM: Intracellular Ca2+ plays pivotal roles in diverse cellular functions,
      including gene transcription that underlies cardiac remodeling during stress
      responses. However, the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) in
      the mediation of cardiac intracellular Ca2+ and hypertrophic growth remains
      elusive. Prior work with neonatal rat ventricular myocytes suggests that
      activation of IP3Rs may be linked to a1 adrenergic receptor (alpha1AR) increased
      stereotyped Ca2+ spark occurrence and global Ca2+ oscillations. Thus, we
      hypothesized that Ca2+ release through IP3Rs was necessary for alpha1AR
      stimulated cardiac hypertrophy. METHODS: We used myoinositol 1,4,5-trisphosphate
      hexakis (butyryloxymethyl) ester (IP3BM), a membrane-permeant ester of IP3, to
      activate IP3Rs directly, and Fluo 4/AM to measure intracellular Ca2+ signaling.
      RESULTS: IP3BM (10 micromol x L(-1)) mimicked the effects of phenylephrine, a
      selective agonist of alpha1AR, in increments in local Ca2+ spark release
      (especially in the perinuclear area) and global Ca2+ transient frequencies. More
      importantly, IP3R inhibitors, 2-aminoethoxydiphenyl borate and Xestospongin C,
      abolished the IP3BM-induced Ca2+ responses, and significantly suppressed alpha1AR
      induced cardiomyocyte hypertrophy assayed by cell size, [3H] leucine
      incorporation and atrial natriuretic factor gene expression, during sustained (48
      h) phenylephrine stimulation. CONCLUSION: These results, therefore, provide
      cellular mechanisms that link IP3R signaling to alpha1AR-stimulated gene
      expression and cardiomyocyte hypertrophy.

PMID- 16787575
TI  - Developmental regulation of intracellular calcium transients during cardiomyocyte
      differentiation of mouse embryonic stem cells.
AB  - AIM: To investigate the developmental regulation of intracellular Ca2+
      transients, an essential event in excitation-contraction coupling, during
      cardiomyocyte differentiation. METHODS: Using the embryonic stem (ES) cell in
      vitro differentiation system and pharmacological intervention, we investigated
      the molecular and functional regulation of Ca2+ handling proteins on the Ca2+
      transients at early, intermediate and later differentiation stages of ES cell
      derived cardiomyocytes (ESCM). RESULTS: Nifedipine, a selective antagonist of L
      type Ca2+ channels, totally blocked Ca2+ transients even in the condition of
      field-electric stimulation in ESCM at three differentiation stages. The Ca2+
      transients of ESCM were also inhibited by both ryanodine [an inhibitor of
      ryanodine receptors (RyRs)] and 2-aminoethoxydipheylborate [2-APB, an inhibitor
      of inositol-1,4,5-trisphosphate receptors (IP3Rs)]. The inhibitory effect of
      ryanodine increased with the time of differentiation, while the effect of 2-APB
      decreased with the differentiation. Thapsigargin, an inhibitor of SR Ca2+-pump
      ATPase, inhibited Ca2+ transients equally at three differentiation stages that
      matched the expression profile. Na+ free solution, which inhibits Na+-Ca2+
      exchanger (NCX) to extrude Ca2+ from cytosol, did not affect the amplitude of
      Ca2+ transients of ESCM until the latter differentiation stage, but it
      significantly enhanced the basal Ca2+ concentration. CONCLUSION: The Ca2+
      transients in ESCM depend on both the sarcolemmal Ca2+ entry via L-type Ca2+
      channels and the SR Ca2+ release from RyRs and IP3Rs even at the early
      differentiation stage; but NCX seems not to regulate the peak of Ca2+ transients
      until the latter differentiation stage.

PMID- 16787576
TI  - Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial
      injury induced by ischemia and reperfusion.
AB  - AIM: Attenuation of mitochondrial Ca2+ ([Ca2+]m), but not cytosolic Ca2+
      ([Ca2+]c), overload improves contractile recovery. We hypothesized that
      attenuation of [Ca2+]m, but not [Ca2+]c, overload confers cardioprotection
      against ischemia/reperfusion-induced injury. METHODS: Infarct size from isolated
      perfused rat heart, cell viability, and electrically-induced Ca2+ transient in
      isolated rat ventricular myocytes were measured. We determined the effects of
      BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both
      [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter
      of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but
      not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. RESULTS:
      Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca2+]m,
      but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury
      observations, indicating the importance of [Ca2+]m in cardioprotection and
      contractile recovery in response to ischemia/reperfusion. CONCLUSION: The study
      has provided unequivocal evidence using a cause-effect approach that attenuation
      of [Ca2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against
      ischemia/reperfusion-induced injury. We also confirmed the previous observation
      that attenuation of [Ca2+]m, but not [Ca2+]c, by ruthenium red improves
      contractile recovery following ischemia/reperfusion.

PMID- 16787577
TI  - Insulin improves cardiomyocyte contractile function through enhancement of
      SERCA2a activity in simulated ischemia/reperfusion.
AB  - AIM: Insulin exerts anti-apoptotic effects in both cardiomyocytes and coronary
      endothelial cells following ischemia/reperfusion (I/R) via the Akt-endothelial
      nitric oxide synthase survival signal pathway. This important insulin signaling
      might further contribute to the improvement of cardiac function after
      reperfusion. In this study, we tested the hypothesis that sarcoplasmic reticulum
      calcium-ATPase (SERCA2a) is involved in the insulin-induced improvement of
      cardiac contractile function following I/R. METHODS: Ventricular myocytes were
      enzymatically isolated from adult SD rats. Simulated I/R was induced by perfusing
      cells with chemical anoxic solution for 15 min followed by reperfusion with
      Tyrode's solution with or without insulin for 30 min. Myocyte shortening and
      intracellular calcium transients were assessed and underlying mechanisms were
      investigated. RESULTS: Reperfusion with insulin (10(-7) mol/L) significantly
      improved the recovery of contractile function (n=15-20 myocytes from 6-8 hearts,
      P<0.05), and increased calcium transients, as evidenced by the increased calcium
      [Ca2+] fluorescence ratio, shortened time to peak Ca2+ and time to 50% diastolic
      Ca2+, compared with those in cells reperfused with vehicle (P<0.05). In addition,
      Akt phosphorylation and SERCA2a activity were both increased in insulin-treated
      I/R cardiomyocytes, which were markedly inhibited by pretreatment of cells with a
      specific Akt inhibitor. Moreover, inhibition of Akt activity abolished insulin
      induced positive contractile and calcium transients responses in I/R
      cardiomyocytes. CONCLUSION: These data demonstrated for the first time that
      insulin improves the recovery of contractile function in simulated I/R
      cardiomyocytes in an Akt-dependent and SERCA2a-mediated fashion.

PMID- 16787578
TI  - Isoprenaline enhances local Ca2+ release in cardiac myocytes.
AB  - AIM: Contraction of cardiac myocytes is controlled by the generation and
      amplification of intracellular Ca2+ signals. The key step of this process is the
      coupling between sarcolemma L-type Ca2+ channels (LCCs) and ryanodine receptors
      (RyRs) in the sarcoplasmic reticulum (SR). Beta-adrenergic stimulation is an
      important regulatory mechanism for this coupling process. But the details
      underlied the global level, which require local Ca2+ release study are still
      unclear. The present study is to explore the effects of beta-adrenergic
      stimulation on local Ca2+ release. METHODS: Using confocal microscopy combined
      with loose-seal patch-clamp approaches, effects of isoprenaline (1 micromol/L), a
      beta-adrenergic agonist, on local SR Ca2+ release triggered by Ca2+ influx
      through LCCs in intact rat cardiac myocytes were investigated. RESULTS:
      Isoprenaline increased the intensity of ensemble averaged local Ca2+ transients,
      the peak of which displayed a typical bell-shaped voltage-dependence over the
      membrane voltages ranging from approximately -40 mV to approximately +35 mV.
      Further analysis showed that this enhancement could be explained by the increased
      coupling fidelity (which refers the increased probability of RyRs activation upon
      depolarization), and the increased amplitude of evoked Ca2+ sparks [due to more
      Ca2+ releases through local RyRs]. In addition, isoprenaline decreased the first
      latency, which displayed a typical 'U ' shaped voltage-dependence, showing the
      available acceleration and synchronization of beta-adrenergic stimulation on
      intracellular calcium release. CONCLUSIONS: Isoprenaline enhances local Ca2+
      release in cardiac myocytes. These results underscore the importance of
      regulation of beta-adrenergic stimulation on local intermolecular signals between
      LCCs and RyRs in heart cells.

PMID- 16787579
TI  - Characteristics of Ca2+-exocytosis coupling in isolated mouse pancreatic beta
      cells.
AB  - AIM: To characterize Ca2+-stimulated exocytosis in isolated mouse pancreatic beta
      cells. METHODS: An improved method was described for isolation of mouse
      pancreatic beta cells by collagenase P. The Ca2+ channel current and the membrane
      capacitance were examined by using the whole-cell patch clamp recording
      technique. RESULTS: Using depolarization and flash photolysis of caged Ca2+ to
      induce Ca2+-dependent exocytosis in beta cell from KM mouse, we have explored the
      characteristics of the Ca2+ channel current and the relationship between Ca2+
      signals and exocytosis. The averaged peak Ca2+ current measured at +20 mV was 
      60+/-6 pA (n=13). CONCLUSION: We characterized three kinetically different pools
      of vesicles in mouse pancreatic beta cells, namely an immediately releasable
      pool, a readily releasable pool, and a reserve pool.

PMID- 16787580
TI  - Localized Ca2+ uncaging induces Ca2+ release through IP3R in smooth muscle.
AB  - AIM: Our previous study indicated that there are two types of Ca2+ release events
      seen in intact mouse bladder tissue. In this study our aim is to investigate the
      mechanism that underlies the phenomena of Ca2+ release in smooth muscle. METHODS:
      Single cells were isolated and tissue segments were prepared by cutting the
      detrusor into 0.1 cm x 0.5 cm strips running along the axis from the neck to the
      fundus. Single cells and intact tissue strips were co-loaded with the Ca2+
      indicator and caged Ca2+ by incubation with 10 micromol/L Fluo-4 AM and DMNP-EDTA
      AM. Fluo-4 AM fluorescence was detected by laser scanning confocal microscopy,
      and local uncaging of DMNP-EGTA was achieved by brief exposure to the output of a
      diode-pumped, Ti:sapphire laser tuned to 730 nm. RESULTS: Local uncaging of caged
      Ca2+ was able to trigger Ca2+ release events in both single cells and tissue
      strips from mouse bladder. The Ca2+ release events could not be blocked by
      ryanodine alone, but the property of the Ca2+ release was markedly altered.
      Surprisingly, in the presence of ryanodine, Xestospongin C completely inhibited
      the Ca2+ release events both in single cell and tissue experiments. CONCLUSION:
      (1) Two photon flash photolysis (TPFP) triggers Ca2+ induced Ca2+ release. This
      process involves release through type 2 ryanodine receptor channels; (2) TPFP
      results in the release of Ca2+ through inositol 1,4,5-trisphosphate receptors in
      the absence of phospholipase C activation.

PMID- 16787581
TI  - Residue Phe266 in S5-S6 loop is not critical for Charybdotoxin binding to Ca2+
      activated K+ (mSlo1) channels.
AB  - AIM: To gain insight into the interaction between the Charybdotoxin (ChTX) and BK
      channels. METHODS: Site-directed mutagenesis was used to make two mutants: mSlo1
      F266L and mSlo1-F266A. The two mutants were then expressed in Xenopus oocytes and
      their effects were tested on ChTX by electrophysiology experiments. RESULTS: We
      demonstrate an equilibrium dissociation constant Kd=3.1-4.2 nmol/L for both the
      mutants mSlo1-F266L and mSlo1-F266A similar to that of the wild-type mSlo1 Kd=3.9
      nmol/L. CONCLUSION: The residue Phe266 does not play a crucial role in binding to
      ChTX, which is opposed to the result arising from the simulation of peptide
      channel interaction.

PMID- 16787582
TI  - Network regulation of calcium signal in stomatal development.
AB  - AIM: Each cell is the production of multiple signal transduction programs
      involving the expression of thousands of genes. This study aims to gain insights
      into the gene regulation mechanisms of stomatal development and will investigate
      the relationships among some signaling transduction pathways. METHODS: Nail
      enamel printing was conducted to observe the stomatal indices of wild type and 10
      mutants (plant hormone mutants, Pi-starvation induced CaM mutants and Pi
      starvation-response mutant) in Arabidopsis, and their stomatal indices were
      analyzed by ANOVA. We analyzed the stomatal indices of 10 Arabidopsis mutants
      were analyzed by a model PRGE (potential relative effect of genes) to research
      relations among these genes. RESULTS: In wild type and 10 mutants, the stomatal
      index did not differ with respect to location on the lower epidermis. Compared
      with wild type, the stomatal indices of 10 mutants all decreased significantly.
      Moreover, significant changes and interactions might exist between some mutant
      genes. CONCLUSION: It was the stomatal intensity in Arabidopsis might be highly
      sensitive to most mutations in genome. While the effect of many gene mutations on
      the stomatal index might be negative, we also could assume the stomatal
      development was regulated by a signal network in which one signal transduction
      change might influence the stomatal development more or less, and the
      architecture might be reticulate. Furthermore, we could speculate that calcium
      was a hub in stomatal development signal regulation network, and other signal
      transduction pathways regulated stomatal development by influencing or being
      influenced by calcium signal transduction pathways.

PMID- 16787583
TI  - Expression of survivin gene in apoptosis induced by dexamethasone in CEM cells.
AB  - OBJECTIVE: The precise mechanism of glucocorticoid-induced apoptosis has not yet
      been elucidated. Survivin, a member of the inhibitors of apoptosis protein
      family, correlates with inhibition of apoptosis, proliferation, angiogenesis and
      multiple drugs resistance. This study aimed to investigate the variation of the
      survivin gene expression in apoptosis induced by dexamethasone (Dex) in the human
      T-lineage acute lymphoblastic leukemia (ALL) cell line, CEM-WT cells. METHODS:
      The logarithmically growing CEM cells cultured in vitro (cell density 2
      x10(5)/mL) were exposed to 0.1, 0.5, 1, 5, and 10 microM Dex, then were collected
      24, 48 and 72 hrs later. Untreated CEM cells were used as Controls. The cell
      viability was determined by trypan blue dye exclusion. Apoptosis was evaluated by
      morphology and flow cytometry. Survivin protein and gene were analyzed by Western
      Blot and RT-PCR. RESULTS: CEM cells growth was obviously inhibited by 0.1, 0.5,
      1, 5, and 10 microM Dex from 48 hrs. The inhibition effect was dose- and time
      dependent. CEM cells treated with Dex (> or = 5 microM) exhibited typical
      apoptotic features. The apoptosis increased after 5 microM Dex treatment in a
      time-dependent manner, with the apoptosis percentage increasing from 14.9% (12
      hrs) to 46.2% (48 hrs). Compared with that of the Control group, the expression
      of survivin protein was down-regulated, with the expression rate of 54.6%, 45.5%,
      15.8% and 9.7% respectively at 12, 24, 48 and 72 hrs after 5 microM Dex
      treatment. 5 microM Dex treatment also resulted in a decrease of survivin mRNA
      expression. The survivin mRNA expression was 76.4%, 67.3%, 55.0%, 49.9%, 38.3%
      and 18.3% of the Control respectively at 6, 12, 24, 48 and 72 hrs after Dex
      treatment. CONCLUSIONS: Apoptosis induced by Dex in CEM cells is associated with
      downregulation of the survivin expression.

PMID- 16787584
TI  - [Mean values of brain natriuretic peptide in 190 healthy children].
AB  - OBJECTIVE: Overseas research has shown the value of brain natriuretic peptide
      (BNP) in the diagnosis and treatment of heart failure in children. However, a
      reference range of BNP values is lacking, limiting its clinical application. This
      study was designed to determine a reference range for children aged 1 to 16
      years. METHODS: Plasma BNP (BNP32, NT-proBNP) concentrations were measured in 190
      healthy children (95 boys and 95 girls) using an enzyme immunoassay. Their age
      ranged from 1 to 16 years (mean=10.6 +/- 4.2 years). RESULTS: The mean plasma
      concentration of BNP32 in 190 children was 51.89 +/- 48.36 pg/mL, with the 10th
      and the 90th percentile rank of 27.00 pg/mL and 75.00 pg/mL respectively. The
      mean plasma concentration of BNP32 in girls was 60.33 +/- 62.91 pg/mL, and 44.22
      +/- 27.14 pg/mL in boys, but no statistical differences were found. The mean
      plasma concentration of NT-proBNP in 190 children was 246.04 +/- 67.27 fmol/mL.
      The girls had slightly higher plasma NT-proBNP levels than the boys, but there
      were no statistical differences between them. Neither plasma BNP32 concentration
      nor NT-proBNP concentration was related to age. CONCLUSIONS: This study first
      reported a reference range of BNP values for healthy Chinese children aged 1-16
      years. Both age and gender are not related to BNP values.

PMID- 16787585
TI  - [Allogeneic hematopoietic stem cell transplantation for the treatment of
      mucopolysaccharidosis type 1: a case report].
AB  - Mucopolysaccharidosis type I (MPS-I) is an inborn error of metabolism with
      progressive multisystem involvement. Hurler syndrome is the most severe form of
      MPS-I that causes progressive deterioration of the central nervous system with
      ensuing death. This study reported the therapeutic effect of allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) on Hurler syndrome in one
      case. The patient was a 25-month-old boy. He underwent allo-HSCT. The donor was
      his elder sister whose HLA-B locus was not matching. The reduced-intensity of
      BuCy conditioning regimen in allo-HSCT for this patient was as follows: busulfan
      3.7 mg/kg daily at 9 to 6 days before transplantation, cyclophosphamide 42.8
      mg/kg daily at 5 to 2 days before transplantation, and rabbit antithymocyte
      globulin 3.5 mg/kg daily at 1, 3, 5, and 7 days before transplantation. Human
      granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem
      cells (CD34+ cells 12.8 x10(6)/kg) were infused and cyclosporine (CSA), short
      course methotrexate, daclizumab and mycophenolate mofetil (MMF) were administered
      to prevent graft-versus-host disease (GVHD). Complete donor-type engraftment was
      confirmed by Short Tandem Repeat-Polymerase Chain Reaction (STR-PCR) on day 14
      after transplantation. Neutrophil and platelet engraftment occurred on days 11
      and 19 after transplantation respectively. Only grade I regimen-related toxicity
      of live and gastrointestinal tract occurred. GVHD and graft failure were not
      observed. After transplantation, the clinical symptoms and the neurocognitive
      function were greatly improved in this patient. It was concluded that allo-HSCT
      was effective for the treatment of MPS-I. The reduced-intensity conditioning
      regimen was helpful to decrease the regimen-related toxicity. Sufficient
      immunosuppressive therapy and adequate hematopoietic stem cells infusion may be
      beneficial to the donor cell engraftment and reducing the incidence of graft
      failure and GVHD.

PMID- 16787587
TI  - [Changes of serum and cerebrospinal fluid insulin-like growth factor-II levels in
      neonates with hypoxic-ischemic encephalopathy].
AB  - OBJECTIVE: Many studies have demonstrated that low levels of insulin-like growth
      factor-I (IGF-I) may be associated with the hypoxic-ischemic brain damage (HIBD)
      and that IGF-I has a neuroprotective effect. The role of IGF-II, a structurally
      and functionally homologous polypeptide with IGF-I, is unclear in HIBD. This
      study was designed to observe the changes of serum and cerebrospinal fluid (CSF)
      IGF-II levels in neonates with hypoxic-ischemic encephalopathy (HIE) and to
      investigate its effects on HIE. METHODS: Serum and CSF IGF-II levels in 41
      neonates with HIE were measured by radioimmunoassay in the acute phase (postnatal
      age 12-24 hrs) and the convalescence phase (postnatal age 10-12 days). The 41 HIE
      neonates included 10 cases of mild, 12 moderate, and 19 severe HIE. Serum samples
      of 10 normal neonates were used as controls. RESULTS: In the acute phase, serum
      IGF-II levels in the Mild HIE group (203.28 +/- 40.09 ng/mL) and the Moderate HIE
      group (192.33 +/- 39.66 ng/mL) were not significantly reduced, but were obviously
      reduced in the Severe HIE group (116.72 +/- 39.50 ng/mL) compared with normal
      controls (229.38 +/- 43.39 ng/mL) (P<0.01). During the convalescence phase, serum
      IGF-II levels in the Mild HIE group (285.53 +/- 49.44 ng/mL) and in the Moderate
      HIE group (278.69 +/- 51.34 ng/mL) increased significantly (P < 0.01); CSF IGF-II
      levels increased in the Mild HIE group from 27.23 +/- 7.82 ng/mL (acute phase) to
      81.58 +/- 9.77 ng/mL (convalescence phase) (P < 0.01) and also increased in the
      Moderate HIE group from 23.43 +/- 7.79 ng/mL (acute phase) to 78.48 +/- 10.44
      ng/mL (convalescence phase) (P < 0.01). The patients from the severe HIE group
      whose neurological symptoms or signs were improved in the convalescence showed
      higher serum and CSF IGF-II levels than in the acute phase (254.08 +/- 48.50
      ng/mL vs 122.21 +/- 46.26 ng/mL; 69.42 +/- 10.20 ng/mL vs 15.05 +/- 7.03 ng/mL; P
      < 0.01). A positive correlation was found between the serum and CSF IGF-II levels
      in the HIE group (r=0.69, P < 0.01). CONCLUSIONS: IGF-II levels in serum and CSF
      are associated with the pathogenesis and the prognosis of neonatal HIE.

PMID- 16787586
TI  - [Effects of birth asphyxia or intrauterine distress on renal functions in
      newborns in the first week of life].
AB  - OBJECTIVE: To investigate the renal function in newborns with birth asphyxia or
      intrauterine distress in the first week of life. METHODS: Sixty full-term
      newborns born between June 2002 and February 2003 were assigned into three
      groups: Control group (healthy newborns), Intrauterine distress group (Apgar
      score > 7), and Birth asphyxia group without intrauterine distress (12 mild
      asphyxia and 8 severe asphyxia) (n=20 each). Urinary levels of alpha1
      microglobulin (alpha1-MG), beta2-microglobulin (beta2-MG) and albumin (Alb) were
      detected by radioimmunoassay at 0-2, 3-4 and 6-7 days after birth. RESULTS: The
      urinary levels of alpha1-MG, beta2-MG and Alb in the Asphyxia group were
      significantly higher than those in the Control group at all time points (P <
      0.05), peaking at 3-4 days after birth. Statistically significant differences
      were found between the severely and mildly asphyxiated newborns for the urinary
      levels of alpha1-MG, beta2-MG and Alb at all time points (P < 0.05). There were
      no significant differences in the urinary levels of alpha1-MG, beta2-MG and Alb
      between the Intrauterine distress and the Control groups at each time point.
      CONCLUSIONS: Birth asphyxia may lead to renal glomerular and tubular impairments
      and it is speculated that the most serious impairment occurs at the 3rd and 4th
      days of life. The severity of renal impairments is associated with the degree of
      asphyxia. The renal function of the newborn appears to be normal following
      intrauterine distress.

PMID- 16787588
TI  - [Regional cerebral oxygen saturation in neonates with meconium aspiration
      syndrome].
AB  - OBJECTIVE: This study examined the changes of regional cerebral oxygen saturation
      (rSO2) by noninvasive near infrared spectrophotometry in neonates with meconium
      aspiration syndrome (MAS). METHODS: Seventy-three full neonates with MAS were
      divided into three groups by respiratory symptoms: asymptomatic group (group 1,
      n=38), common group (group 2, n=28) and severe group (group 3, n=7). Near
      infrared spectrophotometry was used to measure the cerebral rSO2 on days 1, 3, 5
      and 7 after birth. Thirty healthy full-term newborns served as the Control group.
      RESULTS: The cerebral rSO2 of group 1 decreased significantly compared with that
      of the Control group between days 1 and 3 (P < 0.05). The cerebral rSO2 of group
      2 or group 3 was significantly lower than that of group 1 and the Control group
      on days 1, 3 and 5 (P < 0.05). The MAS patients with mild hypoxic-ischemic
      encephalopathy (HIE) had significantly higher brain rSO2 levels than those with
      medium or severe HIE on days 2, 3 and 5 (P < 0.05). CONCLUSIONS: The cerebral
      rSO2 decreased in neonates with MAS. The values for rSO2 correlated with the
      severity of HIE in MAS patients.

PMID- 16787589
TI  - [Role of cerebral computed tomography in the evaluation of brain injury following
      hypoxia in neonates].
AB  - OBJECTIVE: To investigate the role of cerebral computed tomography (CT) in the
      evaluation of the severity of brain injury following hypoxia in neonates.
      METHODS: A total of 114 full-term newborns who had perinatal hypoxia, including
      25 cases of hypoxic-ischemic encephalopathy (HIE), 36 cases of neonatal asphyxia
      and 53 cases of simple intrauterine fetal distress, were enrolled in this study.
      Twenty normal newborns served as the Control group. All had cerebral CT scan at 2
      7 days of age. Neonatal behavior neurological assessment (NBNA) was performed at
      5 days of age. RESULTS: The average NBNA scores were significantly lower and the
      abnormality rate of NBNA was significantly higher in the HIE group than in the
      other three groups (P < 0.05). The Asphyxia and the Distress groups had also
      lower NBNA scores and higher abnormality rate of NBNA than the Control group (P <
      0.05). Twenty-two patients were found to have cerebral CT abnormality in the HIE
      group, but there was only 1 case in the Control group (P < 0.01). The abnormality
      rate of cerebral CT in the Asphyxia and the Distress groups was not statistically
      different from that of the Control group. Twenty-five cases of HIE were divided
      into mild (n=15), medium (n=6) and severe (n=4) by clinical grading but were
      divided into normal (n=3), mild (n=10), medium (n=7) and severe (n=5) by CT
      grading. CT and clinical grading on HIE was not consistent. The sensitivity of CT
      in the diagnosis of mild, moderate and severe HIE was 47%, 33% and 50%
      respectively, the specificity was 70%, 74% and 86% respectively and the accuracy
      was 48%, 64% and 80% respectively. CONCLUSIONS: CT evaluation on mild brain
      injury induced by asphyxia or intrauterine fetal distress is not of any value and
      the role of CT evaluation on the HIE grade is uncertain and doubtful.

PMID- 16787590
TI  - [Serum levels of IL-5 and LTB4 in children with Henoch-Schonlein purpura].
AB  - OBJECTIVE: This study investigated the serum levels of interleukin-5 (IL-5),
      leukotriene B4 (LTB4) and C-reactive protein (CRP) in children with Henoch
      Schonlein purpura (HSP) at different phases to explore the role of IL-5, LTB4 and
      CRP in the pathogenesis of HSP. METHODS: Serum levels of IL-5, LTB4 and CRP in 27
      normal children and 31 children with HSP at the acute phase and the early
      recovery phase were detected using ELISA. RESULTS: The serum levels of IL-5, LTB4
      and CRP in children with HSP were 53.8 +/- 4.2 pg/mL, 95.3 +/- 12.0 pg/mL and
      36.10 +/- 11.78 mg/L, respectively at the acute phase. The values were
      significantly decreased at the early recovery phase (37.8 +/- 3.9 pg/mL, 45.7 +/-
      10.1 pg/mL, 18.35 +/- 6.43 mg/L; P < 0.01), but remained higher than those in
      normal controls (12.7 +/- 3.2 pg/mL, 17.6 +/- 5.7 pg/mL, 4.75 +/- 2.85 mg/L; P <
      0.01). The serum levels of IL-5 and LTB4 positively correlated to the CRP level.
      CONCLUSIONS: The serum levels of IL-5 and LTB4 in children with HSP increased
      during the acute phase and decreased at the early recovery phase, suggesting that
      IL-5 and LTB4 may be involved in the pathogenesis of HSP.

PMID- 16787591
TI  - [Levels of serum brain natriuretic peptide in children with congestive heart
      failure or with severe pneumonia].
AB  - OBJECTIVE: Some research has shown that B-type brain natriuretic peptide (BNF) is
      helpful in differentiating cardiac from pulmonary etiologies of dyspnea in
      adults. This study was designed to investigate whether BNP concentration could be
      similarly applied in children presenting with dyspnea. METHODS: Blood samples
      were collected from 65 children presenting with dyspnea, due to congestive heart
      failure (CHF, n=24), pneumonia (n=23) or pneumonia together with CHF (n=18). The
      samples from 15 healthy children were used as the controls. There were no
      significant differences in age among the four groups. Serum BNP levels were
      measured using ELISA. RESULTS: Serum BNP levels in the CHF group (141.55 +/-
      75.99 pg/mL) were significantly higher than those in the Pneumonia group (26.00
      +/- 14.57 pg/mL; P < 0.01), and the Pneumonia together with CHF group (113.73 +/-
      87.05 pg/mL; P < 0.05), as well as the Control group (19.31 +/- 10.30 pg/mL; P <
      0.01). The patients with pneumonia together with CHF had significantly higher
      serum BNP levels than those of the Pneumonia and the Control groups (P < 0.01).
      There were no significant differences in BNP levels between the Pneumonia and the
      Control groups. The area under the receive operator characteristic (ROC) curve,
      which demonstrated the diagnostic utility of BNP in differentiating CHF from
      pneumonia, was 0.978 (P < 0.01). At a cut-off of 49 pg/mL, BNP had a sensitivity
      of 87.5% and a specificity of 95.8% for differentiating CHF from pneumonia. In
      the 18 patients who were diagnosed with pneumonia together with CHF, 11 had BNP
      levels above 49 pg/mL. The mean levels of BNP of the 11 patients were
      significantly higher than those of the patients with pneumonia (172.08 +/- 56.47
      pg/mL vs 25.00 +/- 14.57 pg/mL; P < 0.01) but were significantly decreased after
      treatment (26.12 +/- 15.71 pg/mL; P < 0.01). CONCLUSIONS: BNP level is of value
      in differentiating cardiac from pulmonary causes of dyspnea in children. BNP
      level is also helpful in assessing whether or not severe pneumonia couples with
      heart failure in children.

PMID- 16787592
TI  - [Childhood upper respiratory infection caused by Mycoplasma pneumoniae].
AB  - OBJECTIVE: This study was designed to investigate the prevalence, clinical
      characteristics and outcome of upper respiratory infection (URI) caused by
      Mycoplasma pneumoniae (MP) in children. METHODS: Pharyngeal cultures for MP
      antibody were performed in 960 children with acute URI. The samples were randomly
      collected from the outpatient room or emergency room (Observed group). Of the
      Observed group, there were 232 cases under 1 year of age, and the remainder, were
      between 1-12 years old. The samples from 100 healthy children aged from 6 months
      to 12 years were used as the Control group. The prevalence of MP infection
      between the two groups was compared. The clinical manifestations and the outcome
      between the patients with MP positive and negative were compared. RESULTS: MP
      antibody was positive in 31.7% (304/960) of the Observed group but only 9.0%
      (9/100) in the Control group (P < 0.05). The URI patients under 1 year of age had
      a lower positive rate of MP than those over 1 year old (P < 0.05). Coughs and
      tonsillitis were more common (P < 0.05), but catarrh, gastroenteritic symptoms,
      herpes, and tetter were rare (P < 0.01) in URI patients with MP positive compared
      with those with MP negative. Pneumonia developed in 14.8% of the patients with MP
      positive but only 7.0% in those with MP negative (P < 0.01). CONCLUSIONS: MP is
      one of the main pathogens of acute URI in children. Acute pharyngotonsillitis
      symptoms are predominately presented in children with MP infection. MP infection
      was commonly seen in children over 1 year old and they are prone to develop
      pneumonia.

PMID- 16787593
TI  - [Value of serum soluble interleukin-2R, interleukin-6 and C-reactive protein in
      the early diagnosis of Kawasaki disease].
AB  - OBJECTIVE: Immunovasculitis is a pathologic process of Kawasaki disease (KD) in
      the early stage and it is more likely to result from abnormal immunoactivation.
      It is thus speculated that the serum levels of some cytokines have changed before
      immunovasculitis occurs, suggesting the cytokines may be useful markers for the
      early diagnosis of KD. In this study, we measured the serum levels of soluble
      interleukin-2 receptors (sIL-2R), interleukin-6(IL-6) and high-sensitive C
      reactive protein (hs-CRP) in patients with KD to evaluate the significance of
      these cytokines in the early diagnosis of KD. METHODS: Serum levels of sIL-2R and
      IL-6 were measured by rapid one-step sandwich enzyme immunoassay and the serum hs
      CRP level was measured by Dade Behring BN ProSpec in 32 KD patients before and
      after intravenous immunoglobulin (IVIG) therapy. Twenty healthy children were
      used as the controls. RESULTS: Before IVIG therapy serum levels of sIL-2R
      (9253.41 +/- 2568.38 pg/mL vs 2161.53 +/- 696.92 pg/mL; P < 0.05), IL-6 (57.19 +/
      45.78 ng/mL vs 7.04 +/- 1.69 ng/mL; P < 0.05) and hs-CRP (117.69 +/- 42.05 mg/L
      vs 1.15 +/- 0.54 mg/L; P < 0.05) in KD patients were significantly higher than
      those in healthy controls. After IVIG therapy in KD patients serum IL-6 levels
      returned to normal and sIL-2R and hs-CRP levels decreased significantly but
      remained significantly higher than controls (P < 0.05). There was a positive
      correlation between sIL-2R and hs-CRP levels (r=0.60, P < 0.01). IL-6 levels
      positively correlated with hs-CRP levels in KD patients before IVIG therapy
      (r=0.68, P < 0.01). CONCLUSIONS: IL-2R, IL-6 and hs-CRP are activated in the
      development of KD, and they may be of important value in the early diagnosis of
      KD.

PMID- 16787594
TI  - [Cerebral venous sinus thrombosis].
AB  - Cerebral venous sinus thrombosis (CVST) rarely occurs in children but has a
      mortality rate as high as 20%-78%. Because the clinical manifestation of this
      disease has no specificity it is easy to be misdiagnosed. This paper reported a
      case of CVST and reviewed the relevant literatures regarding to the pathogenesis,
      clinical and pathological features, diagnosis and treatment. The patient (male, 8
      months old) was referred to the Beijing Children's Hospital with paroxysm
      headache and after vomiting for 50 days and having double visions for 2 days. He
      was definitely diagnosed with CVST by magnetic resonance imaging (MRI) and
      magnetic resonance venography (MRV). His neurological symptoms were improved
      after receiving intravenous urokinase and hormonal therapy for three weeks
      followed by oral anticoagulation. It is concluded that headache and papilledema
      are the most frequent symptoms in CVST and that MRI and MRV may be primal methods
      for the diagnosis of CVST.

PMID- 16787595
TI  - [Long-term effects of early hyperbaric oxygen therapy on neonatal rats with
      hypoxic-ischemic brain damage].
AB  - OBJECTIVE: The application and therapeutic effect of hyperbaric oxygen (HBO) in
      hypoxic-ischemic brain damage (HIBD) remains controversial. Previous studies have
      focused on the early pathological and biochemical outcomes and there is a lack of
      long-term functional evaluation. This study was designed to evaluate the long
      term pathological and behavioral changes of early HBO therapy on neonatal rats
      with HIBD. METHODS: Postnatal 7 days (PD7) rat pups were randomly assigned into
      Control (n=18), HIBD (n=17) and HBO treatment groups (n=17). HIBD was induced by
      ligating the left common carotid, followed by 2 hrs hypoxia exposure in the HIBD
      and HBO treatment groups. The Control group was sham-operated and was not
      subjected to hypoxia exposure. The HBO therapy with 2 atmosphere absolutes began
      0.5-1 hr after HIBD in the HIBD treatment group, once daily for 2 days. The
      spatial learning and memory ability were evaluated by the Morris water maze test
      at PD37 to PD41. The morphological and histological changes of the brain,
      including brain weight, survival neurons, AchE positive unit and NOS positive
      neurons in hippocampal CA1 region, were detected at PD42. RESULTS: The rats in
      the HIBD group displayed significant morphological and histological deficits, as
      well as severe spatial learning and memory disability. In the Morris water maze
      test, the mean escape latency were longer (56.35 +/- 22.37 s vs 23.07 +/- 16.28
      s; P < 0.05) and the probe time and probe length were shorter in the HIBD group
      (29.29 +/- 6.06 s vs 51.21 +/- 4.59 s and 548 +/- 92 cm vs 989 +/- 101 cm; both P
      < 0.05) compared with the Control group. The left brain weight in the HIBD group
      was lighter than that in the Control group (0.601 +/- 0.59 g vs 0.984 +/- 0.18 g;
      P < 0.05). The survival neurons in the hippocampal CA1 region were less (100 +/-
      27/mm vs 183 +/- 8/mm; P < 0.05), as well as the AchE-positive unit and NOS
      positive neurons (18.50 +/- 2.24% vs 27.50 +/- 2.18% and 19.25 +/- 4.33 vs 33.75
      +/- 5.57 respectively; P < 0.05) after HIBD. Early HBO treatment improved the
      abilities of spatial learning and alleviated the morphological and histological
      damage. The mean escape latency (39.17 +/- 21.20 s) was shortened, the probe time
      (36.84 +/- 4.36 s) and the probe length (686 +/- 76 cm) were longer, and the
      brain weight (0.768 +/- 0.85 g), the survival neurons (133 +/- 25/mm) and the
      AchE-positive unit (21.94 +/- 2.73%) increased significantly compared with those
      of the HIBD group (P < 0.05). CONCLUSIONS: Early HBO treatment resulted in a
      protective effect against HIBD-induced long-term brain morphological and
      histological deficits and spatial learning and memory disability.

PMID- 16787596
TI  - [Protective effects of baicalin pretreatment on hypoxic-ischemic brain damage in
      neonatal rats].
AB  - OBJECTIVE: Previous research suggests that dexamethasone (Dex) pretreatment
      protects neonatal rats against hypoxic-ischemic brain damage (HIBD). Some of the
      pharmacological effects of baicalin (a traditional Chinese medicine extracted
      from Scutellaria baicalensis Georgi) are similar to Dex. This study was designed
      to explore the effect of baicalin on the neuronal apoptosis following HIBD in
      neonatal rats. METHODS: Six-day-old Sprague-Dawley rats were randomly assigned
      into Control (without HI), HIBD, Dex-pretreatment and post-treatment, Baicalin
      pretreatment and -post-treatment groups. HIBD was induced by ligating the left
      common carotid artery, followed by exposure to hypoxia. In the pretreatment
      groups either baicalin (16 mg/kg) or Dex (0.1 mg/kg) was administered to the rats
      24 hrs before HIBD; in the post-treatment groups baicalin or Dex was given 30
      minutes after HIBD. The rat pups were sacrificed on postnatal day 10, and brain
      tissues were harvested. Brain water content was determined, morphological changes
      were observed under a light microscope, and neuronal apoptosis was measured by
      terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling
      (TUNEL) staining. RESULTS: The brain water content and the number of apoptotic
      cells were significantly higher in the HIBD group than those of the Control group
      (P < 0.05). Both baicalin and Dex pretreatment decreased the brain water content
      from 88.9 +/- 1.7 % (HIBD group) to 87.4 +/- 0.7% (baicalin) or 87.3 +/- 0.6%
      (Dex) (P < 0.05) and the number of apoptotic cells were reduced from 251 +/- 28
      (HIBD group) to 102 +/- 47 (baicalin) or 75 +/- 26 (Dex) (P < 0.05). Baicalin and
      Dex post-treatment had no effects on the brain water content and the number of
      apoptotic cells. Loss and degeneration of neurons could be observed in the HIBD
      group. Baicalin and Dex pretreatment significantly alleviated neuronal injury,
      but post-treatment did not. CONCLUSIONS: Pretreatment with baicalin, as with Dex,
      has a protective effect against HIBD in neonatal rats, but baicalin or Dex post
      treatment do not reverse the neuronal injuries.

PMID- 16787597
TI  - [Protective effects of 15-methyl-lipoxin A4 on mesangioproliferative nephritis in
      rats].
AB  - OBJECTIVE: To investigate the protective effects of 15-methyl-lipoxin A4 (LXA4)
      on mesangioproliferative nephritis in rats and the possible mechanisms. METHODS:
      Mesangioproliferative nephritis was induced by a single intravenous injection of
      the mouse monoclonal anti-Thy1.1 antibodies (ER4) in 20 rats. Ten nephritic rats
      were injected with 15-methyl-LXA4 at 10 minutes before ER4 antibody injection and
      then 8-hourly until the rats were sacrificed on day 4 after nephritis induction.
      The nephritis was evidenced by presence of proteinuria, histologic examination
      with light microscopy, infiltrating leukocyte assessed by immunofluorescence
      microscopy, and mesangial cell proliferation assessed by proliferation scoring
      and by immunohistochemical staining of proliferating cell nuclear antigen (PCNA).
      Expressions of interleukin (IL)-1beta and IL-6 protein or mRNA in glomeruli were
      determined by radioimmunoassay or RT-PCR, respectively. Phosphorylated
      phosphoinositide 3-kinase (PI3-K), Akt1 and p27(kip1) in glomeruli were analyzed
      by Western Blot. Activities of nuclear factor-kappaB (NF-kappaB) and signal
      transducer and activator of transcription 3 (STAT3) in glomeruli were assessed by
      electrophoretic mobility shift assay (EMSA). RESULTS: There were increases in
      glomerular infiltration of leukocyte, expressions of IL-1beta and IL-6 protein
      and mRNA, and activities of NF-kappaB in nephritic rats between days 1 and 4
      after nephritis induction. The enhanced proteinuria, score of mesangial
      proliferation, glomerular PCNA positive cells, activities of phosphorylated PI3
      K, Akt1 and STAT3, and reduced p27(kip1) expression were found on day 4 after
      nephritis induction. 15-Methyl-LXA4 treatment significantly reduced the
      proteinuria, glomerular infiltration of leukocyte, expressions of IL-1beta and IL
      6 protein and mRNA, score of mesangial proliferation, glomerular PCNA positive
      cells, activities of phosphorylated PI3-K, Akt1, NF-kappaB and STAT3, and
      increased the p27(kip1) expression. CONCLUSIONS: 15-Methyl-LXA4 can markedly
      inhibit the proteinuria, glomerular inflammation, and mesangial cell
      proliferation induced by anti-Thy1.1 antibodies. The inhibition effects are
      related to PI3-K/Akt1/p27(kip1)/cyclin pathway, STAT3 and NF-kappaB pathway
      dependent signal transduction.

PMID- 16787599
TI  - [Effect of basic fibral growth factor on nestin expression in neonatal rats
      following hypoxic-ischemic brain damage].
AB  - OBJECTIVE: Basic fibral growth factor (bFGF) might have a role in the restoration
      and regeneration of injured neurons following hypoxic-ischemic brain damage
      (HIBD), but its mechanism has not been fully elucidated. Nestin is an
      intermediate filament protein expressed in dividing cells during the early stages
      of CNS development, but it can be reinduced in adults during regeneration of
      injured neurons after CNS injury. This study investigated the effect of exogenous
      bFGF on nestin expression in neonatal rats following hypoxia-ischemia (HI) and to
      explore the possible mechanism. METHODS: Eighty-four 7-day-old SD rats were
      randomly assigned into a Sham-operation group, a HIBD group and a bFGF
      intervention group (n=28 each). HIBD was induced by ligation of the left carotid
      artery along with 8% oxygen exposure in neonatal rats from the latter two groups.
      The Sham-operation group was not subjected to HI. The bFGF intervention group
      received an intraperitoneal injection of bFGF daily (4000 U/kg). Each group was
      randomly subdivided into groups sacrificed immediately, at 3, 12 and 24 hrs and
      3, 7 and 14 days after HI (n=4). The expression of nestin in the cerebral cortex,
      hippocampus and extraventricular zone was examined with immunohistochemical
      staining and image quantitative analysis. RESULTS: Nestin was weakly expressed in
      the hippocampus and extraventricular zone and not expressed in the cortex in the
      Sham-operation group. The nestin in the cortex, hippocampus and extraventricular
      zone was significantly increased after HIBD, peaking at 7 days. bFGF treatment
      increased the nestin expression in the cortex, hippocampus and extraventricular
      zone and statistical differences were observed from 1 to 14 days after HI when
      compared with the untreated HIBD group. CONCLUSIONS: Exogenous bFGF can up
      regulate the nestin expression in neonatal rats following HIBD. The effects of
      restoration and regeneration of bFGF on injured neurons may be associated with
      increased nestin expression in neonatal rats.

PMID- 16787598
TI  - [Effect of carbon monoxide and nitric oxide on the apoptosis of hippocampal
      neurons in rats with febrile seizures].
AB  - OBJECTIVE: Febrile seizure (FS) is the most common type of seizure disorders in
      children. Recurrent FS can cause hippocampal neurons injury. At the same time
      heme oxygenase/carbon monoxide (HO/CO) system and nitric oxide synthase/nitric
      oxide (NOS/NO) system were up-regulated and interacted each other. This study
      examined the effects of the two systems on the apoptosis of hippocampal neurons
      in rats with recurrent FS. METHODS: FS was induced in rats by exposure to warm
      water bath (45.2 degrees C), once every 2 days, 10 times in all. Sprague-Dawley
      (SD) rats aged 21 days were randomly assigned into four groups: Control (37
      degrees C water bath exposure), FS, FS + ZnPP-IX (HO inhibitor) and FS + L-NAME
      (NOS inhibitor) groups. The apoptosis of hippocampal CA1 neurons was detected by
      TUNEL. RESULTS: After recurrent FS, the apoptotic cells in the hippocampal CA1
      neurons increased by 225% compared with those in the Control group (P < 0.01).
      The apoptotic cells in the FS+ZnPP-IX group increased by 62% and 425% compared
      with those in the FS and the Control groups (both P < 0.01). The apoptotic cells
      in the FS + L-NAME group decreased by 38% compared with those in the FS group (P
      < 0.01) and increased by 100% compared with those in the Control group (P <
      0.05). CONCLUSIONS: In recurrent FS, exogenous administration of HO inhibitor
      ZnPP-IX may induce an increase of apoptotic cells in hippocampal neurons, while
      NOS inhibitor L-NAME may decrease the apoptotic cells. The results suggest that
      the HO/CO system might alleviate neuronal damage, while NOS/NO system might
      augment neuronal damage.

PMID- 16787600
TI  - [Protective effects of trichosanthin in Herpes simplex virus-1 encephalitis in
      mice].
AB  - OBJECTIVE: Trichosanthin (TCS), a ribosome-inactivating protein extracted from
      the root tuber of Chinese medicinal herb Trichosanthes kirilowii maximowicz, has
      various pharmacological properties including abortifacient, anti-tumor and anti
      virus. This study aimed to evaluate the effects of TCS on infectious brain injury
      induced by Herpes simplex virus-1 (HSV-1) in mice. METHODS: Ninety mice were
      randomly assigned into three groups: Normal control group (n=30), Model group
      (n=30) and TCS-treated group (n=30). Viral encephalitis was induced by
      intracranial inoculation of HSV-1 in the latter two groups. The TCS-treated group
      was injected with TCS 30 minutes before HSV-1 inoculation. The water content of
      brain tissue was measured at 1, 12, 24 and 48 hrs, and at 4 and 7 days after HSV
      1 inoculation. The viral titer of brain tissue and brain histopathological
      changes were detected at 7 days after HSV-1 inoculation. The neurological
      deficient scores were determined daily. RESULTS: The water content of brain
      tissue in the TCS-treated group between 48 hrs and 7 days after HSV-1 inoculation
      was significantly lower than that in the Model group (P < 0.05), although it was
      significantly higher than that in the Normal control group (P < 0.05). The viral
      titer of brain tissue in the TCS-treated group was markedly lower than that in
      the Model group (1.16 +/- 0.45 vs 2.89 +/- 0.44; P < 0.05) 7 days after HSV-1
      inoculation. The neurological deficient scores of the TCS-treated group after 24
      hrs of HSV-1 inoculation were significantly lower than that in the Model group
      but were higher than those of the Normal control group. TCS treatment resulted in
      alleviated pathological changes of brain tissue compared with the Model group 7
      days after HSV-1 inoculation. CONCLUSIONS: TCS has protective effects against
      infectious brain injury induced by HSV-1 in mice.

PMID- 16787601
TI  - [Investigation of hospital infection in the pediatric department of a general
      hospital].

PMID- 16787602
TI  - [Drug resistance of extended-spectrum beta-lactamase-producing bacteria in
      children with infectious diseases].

PMID- 16787603
TI  - [Effect of cardiopulmonary bypass on platelet membrane glycoprotein in children].

PMID- 16787604
TI  - [Atomization inhalation of ambroxol as an auxiliary therapy for severe pneumonia
      in neonates].

PMID- 16787605
TI  - [A case report of glutaric acidemia].

PMID- 16787606
TI  - [A case report of methylmalonic acidemia].

PMID- 16787607
TI  - [Neonatal hyperthyroidism: report of 2 cases].

PMID- 16787608
TI  - [A case report of kidney failure caused by amoxicillin sodium].

PMID- 16787609
TI  - [A case report of Kasabach-Merritt syndrome].

PMID- 16787610
TI  - [Research advance on childhood chronic cough].

PMID- 16787611
TI  - [Myofibroblast and hyperoxia lung injury].

PMID- 16787612
TI  - Tuberculosis control in Pakistan: current issues and challenges.

PMID- 16787613
TI  - The frequency of postdural puncture headache in different age groups.
AB  - OBJECTIVE: To compare the frequency of postdural puncture headache (PDPH) in
      younger and older age groups i.e. 30-50 years and 51-75 years in patients
      undergoing spinal anaesthesia. DESIGN: Cross-sectional comparative study. PLACE
      AND DURATION OF STUDY: Anesthesia Department of Hayatabad Medical Complex,
      Peshawar, from June to December 2002. PATIENTS AND METHODS: Two hundred patients,
      fulfilling the American Society of Anesthesiologist (ASA) I and II criteria, were
      included in the study and the results of PDPH in both age groups were compared
      and Chi-square test was applied. The level of significance was significant, if
      the p-value was less than 0.05. RESULTS: The occurrence of PDPH was more in young
      patients i.e. 30 patients (30%) in group A, as compared to 5 patients (5%) in
      group B (p<0.05) Female patients had higher frequency of PDPH in both groups. In
      group A, 20 female patients (40%) had PDPH as compared to 10 male patients (20%),
      while in group B, 4 female patients (8%) had PDPH as compared to 1 male patient
      (2%). CONCLUSION: The frequency of postdural puncture headache (PDPH) was less in
      older age group than younger age group and more frequent in females than males.

PMID- 16787614
TI  - Cord blood leptin levels in Pakistani newborns: relationship with birth weight,
      length and occipitofrontal circumference.
AB  - OBJECTIVE: To determine the serum leptin levels in cord blood of Pakistani
      newborns and to ascertain the relationship between serum leptin and
      anthropometric parameters i.e. birth weight, length and OFC. STUDY DESIGN: A
      cross-sectional study. PLACE AND DURATION: Lady Dufferin Hospital and Ziauddin
      Hospital, Karachi from 1999 to 2000. PATIENTS AND METHODS: Leptin concentration
      was measured in 110 newborns of mothers of normal antenatal history from venous
      cord blood, using Active Elisa Kit (DSL-10-23100). Samples were selected
      according to availability. RESULTS: Mean birth weight, length and occipitofrontal
      circumference (OFC) were 3.0+/-0.4 kg, 48.7+/-2.3 cms and 33.1+/-0.8 cms,
      respectively. Mean serum leptin levels was 10.0+/-7.5 ng/ml. Serum leptin levels
      were found to be positively correlated with birth weight (r=0.16, p=0.04), and
      OFC (r=0.33, p<0.01), whereas no significant relationship was found with length
      of the babies. CONCLUSION: The reported results suggest that leptin may play role
      in newborns body weight and energy expenditure as in adults and children.

PMID- 16787615
TI  - Efficacy of rifampicin in eradication of carrier state of Staphylococcus aureus
      in anterior nares with recurrent furunculosis.
AB  - OBJECTIVE: To compare the frequency of detection of Staphylococcus aureus carrier
      state in anterior nares of the patients suffering from recurrent furunculosis
      with the normal population and to determine the efficacy of rifampicin in
      eradication of the carrier state. DESIGN: Quasi-experimental study. PLACE AND
      DURATION OF STUDY: Skin Department of Combined Military Hospital, Peshawar and
      Multan, from March 2004 to December 2005. PATIENTS AND METHODS: The study
      consisted of 80 individuals. They were placed in two groups. Group I comprised of
      40 patients suffering from recurrent furuncles and group II included 40 healthy
      adults, kept as controls. Nasal swab was taken from the individuals belonging to
      both the groups, when they first reported to skin OPD. The patients who were
      suffering from furuncles were treated with co-amoxiclav 375 or 625 mg three times
      a day. The patients in whom S. aureus carrier state was detected were again
      divided into two groups. Group 1 was prescribed rifampicin 450-600 mg daily
      (depending on the body weight) for 10 days, while the group 2 was not offered any
      treatment. After this course, a second nasal swab was taken and submitted for
      cultures. RESULTS: Among the 40 patients belonging to group I, S. aureus carrier
      state was detected in 23 (57.5%), while in group II the carrier state was found
      in 8 (20%) individuals (p<0.001). Among the 13 patients who received rifampicin,
      10 got cured of carrier state, while in 3 patients nasal swab was still positive
      after a course of rifampicin. In 10 patients, who were not offered any treatment,
      the nasal swabs remained positive (p<0.001). These patients were followed-up in
      skin OPD for another 3 months, and did not develop any recurrence of the
      infection. CONCLUSION: Nasal swab for detection of S. aureus carrier state should
      be done in all patients of recurrent furunculosis. If the nasal swab culture is
      positive, then as the infection gets cured, the patients should receive a course
      of rifampicin for 10 days. This may eradicate the carrier state in majority of
      cases and prevent the recurrence of the infection.

PMID- 16787616
TI  - Dural sinus thrombosis: frequency and imaging diagnosis.
AB  - OBJECTIVE: To determine the frequency of dural sinus thrombosis (DST) and
      highlight diagnostic importance of its subtle imaging findings in patients
      presenting for workup of their varied neurologic complaints and symptoms. STUDY
      DESIGN: Observational case series. STUDY PERIOD: June 2002- May 2005. PATIENTS
      AND METHODS: All new patients undergoing cranial computed tomography (CT) and
      magnetic resonance (MR) imaging were included in this study which consisted of
      1676 consecutive subjects with 1780 examinations. These were reviewed in real
      time on monitors (as they were being performed) for evidence of DST before
      printing of hard copies prior to disposition of patients. CT studies were
      performed on Toshiba Auklet scanner with 5 mm thick axial slices and 1 cm inter
      slice gap. MR imaging was performed on 1.5 Tesla Toshiba Visart scanner with T1
      and T2 weighted (T1 and T2W), spin echo, FLAIR and post contrast T1 weighted
      (T1W) imaging in multiple planes. Subjects with inconclusive but suspicious
      conventional imaging (CT, MR) were evaluated by magnetic resonance venography
      (MRV). Patients presenting for follow-up of established diagnoses including
      neoplasia, arterial infarcts, hypertensive parenchymal haemorrhages and
      postsurgical status were excluded. RESULTS: Delta and empty delta were the most
      commonly observed CT and MR signs diagnostic of DST on pre and postcontrast
      images and were present in 43 patients. Thrombus was also directly visible within
      lumen of superior sagittal, transverse and sigmoid sinuses on T1W MR images in 21
      individuals. In 12 patients, these signs were either absent or too subtle to be
      conclusive. However, presence of venous haemorrhagic or non-haemorrhagic brain
      parenchymal edematous lesions prompted further evaluation by MRV, which confirmed
      presence of DST in these subjects as well. As a result, a total of 55 patients
      with a frequency of 3.3% were diagnosed and treated for DST. CONCLUSION:
      Frequency of DST in patients with neurological complaints and symptoms is 3.3%,
      which is significantly higher than has been clinically suspected or recognized.
      On routine CT and MR studies, diagnostic imaging signs, while highly specific for
      DST, can be absent or may be masked due to technical factors or associated
      complications. Presence of brain parenchymal venous haemorrhagic or non
      haemorrhagic edematous lesions should prompt judicious and close scrutiny of
      images on monitors by changing viewing parameters to detect subtle signs of DST.
      If still in doubt, MRV must be pursued for definitive diagnosis.

PMID- 16787617
TI  - Role of pathological cardiotocography in evaluating fetal well-being.
AB  - OBJECTIVE: To determine the frequency of pathological pattern of cardiotocography
      (C.T.G) in antepartum and intrapartum period and to evaluate the significance of
      those patterns in determining fetal well-being. DESIGN: Analytical study. PLACE
      AND DURATION OF STUDY: The study was conducted at Lady Dufferin Hospital, Karachi
      from February 2000 to January 2001. PATIENTS AND METHODS: All women with
      singleton pregnancies of >35 weeks gestation and cephalic presentations were
      electronically monitored in antepartum and intrapartum period and those with
      pathological trace were identified according to International Federation of
      Obstetricians and Gynaecologists (FIGO) classification. After delivery, Apgar
      score, fetal cord, blood gas values and neonatal intensive care unit admission
      duration were examined as the main outcome measures. RESULTS: Among the 3701
      patients who qualified for the study, 60 (1.62%) had tracing, classified as
      pathological, of which 44 (73%) were in the intrapartum and 16 (27%) in the
      antepartum period. Out of these 60 patients, 53 (88.33%) were delivered alive
      while neonatal death (NNDs) occurred in 9 (16.9%) of the live born babies. There
      were 07 (11.6%) still births. In 53 of live born babies, Apgar score was <7 at 1
      minute in 34 (64.15 %), while it was >7 at 1 minute in 19 (35.84%). Low Apgar
      score persisted at 5 minutes in 10 (18.86%) cases of pathological CTG. Out of
      these 10, there were 3(30%) NNDs, while 6 (13.95%) NNDs occurred in those whose
      apgar had improved to >7 at 5 minute (P=0.9). Cord pH results were available in
      31 (58.49 %) cases and were acidotic (<7.20) in 16 (51.61%), pre-acidotic (7.20
      7.25) in 9 (29.03%) and normal (7.25-7.35) in 6 (19.35 %). All alive born babies
      with a pathological CTG tracing were admitted in NICU as per hospital policy. The
      duration of admission was less than 24 hours in 15 (28.30 %), 2-4 days in 26
      (49%) and more than 4 days in 12 (22.64%). CONCLUSION: In this series, an
      increased frequency of detectable hypoxia on CTG was observed during the
      intrapartum period as compared to the antepartum period, however, no significant
      association was found between a pathological CTG recording, fetal APGAR score and
      acidemia, if a pathological trace is used alone to assess fetal well-being. An
      increased cesarean section rate in babies with a pathological CTG stresses on the
      need for additional tests to differentiate hypoxic from non-hypoxic fetuses thus
      avoiding unnecessary intervention.

PMID- 16787618
TI  - Comparison of blood protein levels between diabetic and non-diabetic patients
      with retinopathy.
AB  - OBJECTIVE: To compare serum protein levels between diabetic and non-diabetic
      patients with retinopathy. STUDY DESIGN: Comparative study. PLACE AND DURATION:
      Ziauddin Medical University and Jinnah Postgraduate Medical Centre, Karachi,
      Pakistan, from 2000 to 2002. PATIENTS AND METHODS: Sixty patients were selected.
      Among them, 21 were diabetic patients without any clinical evidence of chronic
      diabetic complications; 20 were diabetic patients with retinopathy and 19 were
      non-diabetic patients with retinopathy. Twenty-one apparently normal, age, gender
      and weight-matched control subjects were also inducted. All these patients were
      selected on clinical grounds. Blood values, fasting plasma glucose, glycosylated
      hemoglobin, serum fructosamine, glycosylated plasma protein, hexosamine, sialic
      acid and total serum proteins were determined and compared. RESULTS: Fasting
      plasma glucose was high in all diabetic patients and correlated significantly
      with glycosylated hemoglobin, glycosylated plasma proteins and serum fructosamine
      concentrations. Fasting plasma glucose, glycosylated hemoglobin, glycosylated
      plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum
      protein were increased in diabetic patients with retinopathy and diabetic
      patients without any complications. These values were not different in diabetic
      patients with retinopathy and diabetic patients without chronic complications as
      compared with control subjects. Alpha-1 and alpha-2 globulins were significantly
      increased in diabetic patients with retinopathy, diabetic patients without
      complications and non-diabetic patients with retinopathy as compared with control
      subjects. Beta globulin was significantly increased in diabetic patients with
      retinopathy as compared with non-diabetic patients with retinopathy, diabetic
      patients without complication and control subjects. Gamma globulin was
      significantly decreased in diabetic and non-diabetic patients with retinopathy.
      CONCLUSION: Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma
      proteins, serum fructosamine, sialic acid, hexosamine and total serum protein
      were increased in diabetic patients with and without complications but these
      parameters remained within normal limits in non-diabetic patients with
      retinopathy. The decrease in gamma globulins may be associated with a
      retinopathy.

PMID- 16787619
TI  - Patterns of argyrophilic nucleolar organiser regions in pleural and peritoneal
      effusions.
AB  - OBJECTIVE: To evaluate AgNOR size and dispersion as alternate methods to AgNOR
      counts in order to differentiate malignant from non-malignant effusions. DESIGN:
      Comparative study. PLACE AND DURATION OF STUDY: Department of Pathology,
      Postgraduate Medical Institute, Lahore, from January 2003 to June 2004. MATERIALS
      AND METHODS: A total of 240 samples of pleural and peritoneal effusions were
      centrifuged, deposits smeared on slides and stained with H and E and AgNOR stain.
      The diagnosis of malignancy or otherwise was made on H and E staining. AgNOR
      counts, variation in size and dispersion of AgNOR dots in smears were graded and
      compared in malignant and non-malignant effusions. RESULTS: Mean AgNOR counts of
      11.47+/-3.60 and 11.04+/-3.89 in malignant pleural and peritoneal effusions,
      respectively, were significantly (p<0.0001) greater as compared with counts of
      3.36+/-0.69 and 3.35+/-0.66 in non-malignant effusions. AgNOR size and dispersion
      were of higher grade in significantly greater proportion of malignant as compared
      with non-malignant effusions (p<0.0001). CONCLUSION: Typing of AgNOR size and
      dispersion was found to be an easy and reproducible alternative to traditional
      AgNOR counts for differentiating malignant from non-malignant effusions. These
      parameters should be correlated with already established but expensive techniques
      of AgNOR area and size imaging by electron microscopy and flow cytometry, as an
      economical alternative.

PMID- 16787620
TI  - Mental distress in mothers of child psychiatric patients.
AB  - OBJECTIVE: To determine whether caring for a child with mental health issues
      could lead to mental distress among mothers. DESIGN: Cross-sectional study. PLACE
      AND DURATION: Outpatient Clinics of The Aga Khan University Hospital and PNS
      Shifa Hospital, Karachi, from January to June 2005. PATIENTS AND METHODS: A total
      of 238 consecutive mothers bringing their children to child psychiatric and
      pediatric clinics were recruited over a 6-month period. As per inclusion
      criteria, 106 mothers of child psychiatric patients were compared to 132 mothers
      taken from pediatric clinics. They were asked to fill out a psychiatric screening
      instrument (WHO SRQ-20). Mothers' mental distress (score>or=10 on SRQ-20) and
      other potential risk or protective factors were measured. RESULTS: Mental
      distress among mothers determined by WHO SRQ-20 was associated with their child
      attending a psychiatric clinic (odds ratio 2.51, 95% confidence interval 1.38
      4.51). This association remained significant for age of mother being less than 30
      years. No significant association was found with the number of children and
      duration of marriage. CONCLUSION: Mental distress among mothers is associated
      with the child having psychiatric problems. These mothers may represent a group
      who are at higher risk of depression. Early recognition and treatment of mental
      health problems in mothers may help reduce psychiatric morbidity in children.

PMID- 16787621
TI  - Scrofuloderma neck with chest wall abscess.
AB  - Cutaneous tuberculosis (TB) is among the uncommon varieties of tuberculosis but
      it is also on the rise, commensurate with the general resurgence of the disease.
      A case of scrofuloderma of neck with tuberculous abscess of anterior chest wall
      is, hereby, reported. The patient presented with a non-healing ulcer of neck with
      swelling of anterior chest wall, which responded to antituberculous treatment.
      This complication of scrofuloderma neck is very rare and should be kept in mind
      in the differential diagnosis of such lesions.

PMID- 16787622
TI  - Tracheal inujry due to blunt chest trauma: a rare surgical emergency.
AB  - Tracheal injury is a rare complication of blunt chest trauma. The patients
      usually present with signs of respiratory distress. Primary repair is the
      treatment of choice in case of large defects, while small tears can be managed
      conservatively. Immediate operation is recommended to improve deteriorating
      pulmonary function. The decrease in mortality and long-term morbidity depends on
      early diagnosis. We report a case of tracheal injury due to non-penetrating
      thoracic trauma which was successfully managed with surgery.

PMID- 16787623
TI  - Primary non-Hodgkin's lymphoma of vagina associated with pregnancy.
AB  - We report a case of non-Hodgkin's lymphoma (NHL) in 23 years old, 36 weeks
      pregnant female, who presented with a swelling in the vagina. Biopsy of the
      lesion led to profuse haemorrhage and emergency caesarean-section along with
      bilateral ligation of internal iliac arteries were required. Recovery was smooth
      and she was discharged from the hospital on the 5th postoperative day.
      Histopathology revealed non-Hodgkin's lymphoma, diffuse large B cell type
      (DLBCL). Further treatment by medical oncologist led to complete resolution of
      the tumour at three months.

PMID- 16787624
TI  - Osteolytic torcular lesion.
AB  - Torcular lesion encroach supratentorial and infratentorial compartments saddling
      or invading the big sinuses leading to torrential bleeding, which may need repair
      with venous or arterial graft. A case is, hereby, reported that presented with
      headache and an occipital swelling. CT scan showed torcular osteolytic tumor
      extending out beneath the scalp and into the posterior cranial fossa and causing
      fourth ventricular blockage. It needed two-stage surgery for complete excision.
      All the big venous sinuses near the lesion were protected. The dural gap was
      filled with fascia lata graft. Histopathology report revealed as malignant tumor
      of bony origin.

PMID- 16787625
TI  - A familial hypomagnesemia--hypercalciuria (Manz syndrome).
AB  - We report a case of a rare inherited tubular disorder of linked transport of
      magnesium and calcium at the level of ascending limb of loop of Henle,
      characterized by hypomagnesemia, hypercalciuria and nephrocalcinosis, known as
      "Manz syndrome," who presented with polyuria, nystagmus and recurrent episodes of
      tetany with radiological evidence of rickets and nephrocalcinosis.

PMID- 16787626
TI  - Granulomatous mastitis: surgical outcomes.
AB  - OBJECTIVE: To report the clinical and pathological features and surgical
      treatment outcomes of patients with granulomatous mastitis. DESIGN: Case series.
      PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital,
      between 1999-2003. PATIENTS AND METHODS: Data of 16 patients with granulomatous
      mastitis treated surgically by total excision with disease-free margins were
      reviewed. Patients given additional medical therapy or treated with mastectomy
      because of the size and extent of the disease were excluded. RESULTS: The mean
      age of patients at the time of diagnosis was 31.8 (range: 22-45 years). All
      patients were diagnosed from the pathological tissue specimens obtained by
      surgery. Clinical and radiological examinations suggested breast carcinoma in
      82.1% patients. Except one patient who developed a fistula from the incision
      which was treated again with surgery, no other complications were noted,
      including recurrence of disease during a median follow-up period of 12.8 months
      (range: 4-30 months). CONCLUSION: Although granulomatous mastitis is a rare
      benign breast disease, it usually mimics breast carcinoma both clinically and
      radiologically, making the diagnosis difficult and challenging. As long as good
      cosmetic results can be achieved, surgical excision is quick, safe and effective
      treatment method for idiopathic granulomatous mastitis.

PMID- 16787627
TI  - Jelly belly test.
AB  - A technique is described as how to appreciate urethral obstruction prior to
      attempt at catheterization to avoid injury to urethra. In this technique
      anesthetic jelly is administered through external urinary meatus, which leads to
      distension of distal urethra in case of obstruction.

PMID- 16787628
TI  - Current challenges in adherence to clinical guidelines for antibiotic prophylaxis
      in surgery.
AB  - To study the impact of guidelines on surgical antibiotic prophylaxis in clinical
      practice, barriers involved in adherence to guidelines and how to overcome the
      same. METHODS: Literature pertaining to prophylactic antibiotic usage was
      searched. Medscape, Medline, Cochrane, Surgical Infection Prevention (SIP)
      project databases were reviewed. Recent articles from relevant journals, texts,
      and standard guidelines were also studied. RESULTS: Local guidelines seem more
      likely to be accepted and followed than those developed nationally. Major
      barriers involved in adherence to guidelines include lack of awareness about the
      guidelines, general perception of guideline as a bureaucratic rather than
      educational tool. Some practitioners perceive guidelines as "cookbook medicine"
      that does not permit them to make their own medical decisions. Other barriers are
      complex, multi-step systems that create confusion, decrease accountability.
      Methods for guideline adherence include surveillance and data analysis, new
      systems to facilitate documentation and improving workflow, education regarding
      current evidence-based guidelines and promoting the development of local
      guidelines or protocol, development and implementation of reminders to facilitate
      adherence to the local guidelines. CONCLUSION: A multidisciplinary steering team
      of surgeons, infectious disease specialists, pharmacists, anesthesiologists,
      microbiologists and nurses should develop local guidelines suitable to their
      institution and methods for adherence to prevent the surgical site infections.
      The gap between evidence-based guidelines and practice must be addressed in order
      to achieve optimal practice in this domain.

PMID- 16787629
TI  - Pathway to psychiatric care in Karachi.

PMID- 16787630
TI  - Faulty endotracheal tube connectors can be dangerous.

PMID- 16787632
TI  - Attention deficit and hyperactivity disorder tendency and unintentional injury
      among adolescents in China.
AB  - This study aims to investigate the association between ADD tendency, with or
      without hyperactivity, and all types of unintentional injuries among adolescents.
      This study was a population-based health survey utilising a two-stage random
      cluster sampling design. The study was conducted among high school students in
      Nanning, the capital city of the Guangxi Province, China. 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. Information on ADD was collected by
      trained health professional via personal interviews. Other information, including
      unintentional injury was collected via a self-report health survey questionnaire.
      One thousand and twenty-nine (n = 1429) students were recruited with 115 (7.9%)
      identified as having a high ADD tendency, and 340 (22.6%) reported as having
      experienced an injury in the last 3 months. After adjusting for other potential
      confounding factors, results from the logistic regression analyses indicated that
      adolescents who scored high on the ADD tendency had an increased risk of injury
      by about 70% as compared to those who scored low (OR = 1.68, 95%CI = 1.18-2.40).
      ADD tendency has been identified as a potential risk factor of injury among
      adolescents. Screening for risk factors can be considered as a potential
      preventive strategy.

PMID- 16787631
TI  - Reductions in driver speed using posted feedback of speeding information: social
      comparison or implied surveillance?
AB  - Reducing driver speed has an essential role to play in traffic safety. This study
      measured the effect of a roadside sign, in a 50 km/h zone, that consecutively
      displayed one of three messages: The average speed at the site: this message was
      designed to induce "social comparison" whereby drivers may reduce their speed in
      order to comply with the behaviour of the majority. A warning that drivers'
      speeds were being measured: this was intended to imply surveillance whereby
      drivers may reduce speed in order to avoid possible enforcement action. A
      combination of both messages, to see if both together would have a greater effect
      than either alone. The speed of drivers travelling along a busy urban road
      (11,500 cars daily in each direction) was measured using inductive loop
      detectors. The proportion of drivers travelling 60 km/h or less increased with
      all three messages, suggesting that both social comparison and implied
      surveillance are mechanisms by which driver speed may be reduced. However, the
      speed reductions were not as great as in previous studies of feedback signs. This
      may be due to differences in the existing safety culture.

PMID- 16787633
TI  - Retail alcohol monopolies, underage drinking, and youth impaired driving deaths.
AB  - OBJECTIVE: To explore associations of state retail alcohol monopolies with
      underage drinking and alcohol-impaired driving deaths. DATA: Surveys on youth who
      drank alcohol and binge-drank recently and their beverage choices; census of
      motor vehicle fatalities by driver blood alcohol level. METHODS: Regressions
      estimated associations of monopolies with under-21 drinking, binge drinking,
      alcohol-impaired driving deaths, and odds a driver under 21 who died was alcohol
      positive. RESULTS: About 93.8% of those ages 12-20 who consumed alcohol in the
      past month drank some wine or spirits. In states with a retail monopoly over
      spirits or wine and spirits, an average of 14.5% fewer high school students
      reported drinking alcohol in the past 30 days and 16.7% fewer reported binge
      drinking in the past 30 days than high school students in non-monopoly states.
      Monopolies over both wine and spirits were associated with larger consumption
      reductions than monopolies over spirits only. Lower consumption rates in monopoly
      states, in turn, were associated with a 9.3% lower alcohol-impaired driving death
      rate under age 21 in monopoly states versus non-monopoly states. Alcohol
      monopolies may prevent 45 impaired driving deaths annually. CONCLUSIONS:
      Continuing existing retail alcohol monopolies should help control underage
      drinking and associated harms.

PMID- 16787634
TI  - Gingival crevicular fluid transforming growth factor-beta1 in several forms of
      periodontal disease.
AB  - BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) has significant
      effects on periodontal host response regulation. Limited knowledge on the role of
      TGF-beta(1) in various periodontal disease types and particularly in advanced
      periodontitis forms warranted the present study. The aim of the present study was
      to evaluate the gingival crevicular fluid (GCF) TGF-beta(1) levels in patients
      with different forms of periodontal disease. METHODS: GCF TGF-beta(1) levels were
      investigated in 32 chronic periodontitis (CP), 30 generalized aggressive
      periodontitis (G-AgP), 15 gingivitis patients and 16 periodontally healthy
      subjects. Periodontal status was evaluated by measuring probing depth, clinical
      attachment loss, plaque and bleeding on probing. TGF-beta(1) levels were analyzed
      by enzyme-linked immunosorbent assay. The results were expressed in terms of
      total amount (pg) and concentration (pg/microl). RESULTS: G-AgP and CP groups had
      significantly elevated GCF TGF-beta(1) total amount compared to healthy group
      (p<0.008). Moreover, GCF TGF-beta(1) total amount of G-AgP group was
      significantly higher than that of gingivitis group (p<0.008). G-AgP and CP groups
      had similar GCF TGF-beta(1) total amount (p>0.008). Significant correlation was
      found between GCF TGF-beta(1) total amount and all clinical periodontal
      parameters (p<0.05). CONCLUSIONS: The results of the present study suggest
      contribution of TGF-beta(1) to the pathogenesis of advanced chronic and
      aggressive periodontitis. TGF-beta(1) may thus be one of the components
      modulating exaggerated host response together with other major mediators of
      inflammation.

PMID- 16787635
TI  - Consequences of the structure of the cytochrome b6f complex for its charge
      transfer pathways.
AB  - At least two features of the crystal structures of the cytochrome b6f complex
      from the thermophilic cyanobacterium, Mastigocladus laminosus and a green alga,
      Chlamydomonas reinhardtii, have implications for the pathways and mechanism of
      charge (electron/proton) transfer in the complex: (i) The narrow 11 x 12 A portal
      between the p-side of the quinone exchange cavity and p-side plastoquinone/quinol
      binding niche, through which all Q/QH2 must pass, is smaller in the b6f than in
      the bc1 complex because of its partial occlusion by the phytyl chain of the one
      bound chlorophyll a molecule in the b6f complex. Thus, the pathway for trans
      membrane passage of the lipophilic quinone is even more labyrinthine in the b6f
      than in the bc1 complex. (ii) A unique covalently bound heme, heme cn, in close
      proximity to the n-side b heme, is present in the b6f complex. The b6f structure
      implies that a Q cycle mechanism must be modified to include heme cn as an
      intermediate between heme bn and plastoquinone bound at a different site than in
      the bc1 complex. In addition, it is likely that the heme bn-cn couple
      participates in photosytem I-linked cyclic electron transport that requires
      ferredoxin and the ferredoxin: NADP+ reductase. This pathway through the n-side
      of the b6f complex could overlap with the n-side of the Q cycle pathway. Thus,
      either regulation is required at the level of the redox state of the hemes that
      would allow them to be shared by the two pathways, and/or the two different
      pathways are segregated in the membrane.

PMID- 16787636
TI  - Mitochondrial potassium channels: from pharmacology to function.
AB  - Mitochondrial potassium channels, such as ATP-regulated or large conductance Ca2+
      -activated and voltage gated channels were implicated in cytoprotective
      phenomenon in different tissues. Basic effects of these channels activity include
      changes in mitochondrial matrix volume, mitochondrial respiration and membrane
      potential, and generation of reactive oxygen species. In this paper, we describe
      the pharmacological properties of mitochondrial potassium channels and their
      modulation by channel inhibitors and potassium channel openers. We also discuss
      potential side effects of these substances.

PMID- 16787637
TI  - MTERF3, the most conserved member of the mTERF-family, is a modular factor
      involved in mitochondrial protein synthesis.
AB  - The MTERF-family is a wide family of proteins identified in Metazoa and plants
      which includes the known mitochondrial transcription termination factors. With
      the aim to shed light on the function of MTERF-family members in Drosophila, we
      performed the cloning and characterization of D-MTERF3, a component of the most
      conserved group of this family. D-MTERF3 is a mitochondrial protein of 323 amino
      acids. Sequence analysis in seven different organisms showed that the protein
      contains five conserved "mTERF-motifs", three of which include a leucine zipper
      like domain. D-MTERF3 knock-down, obtained by RNAi in D.Mel-2 cells, did not
      affect mitochondrial replication and transcription. On the contrary, it decreased
      to a variable extent the rate of labelling of about half of the mitochondrial
      polypeptides, with ND1 being the most affected by D-MTERF3 depletion. These
      results indicate that D-MTERF3 is involved in mitochondrial translation. This
      role, likely based on protein-protein interactions, may be exerted either through
      a direct interaction with the translation machinery or by bridging the
      mitochondrial transcription and translation apparatus.

PMID- 16787638
TI  - Identification of primary tumors of brain metastases by SIMCA classification of
      IR spectroscopic images.
AB  - Brain metastases are secondary intracranial lesions which occur more frequently
      than primary brain tumors. The four most abundant types of brain metastasis
      originate from primary tumors of lung cancer, colorectal cancer, breast cancer
      and renal cell carcinoma. As metastatic cells contain the molecular information
      of the primary tissue cells and IR spectroscopy probes the molecular fingerprint
      of cells, IR spectroscopy based methods constitute a new approach to determine
      the origin of brain metastases. IR spectroscopic images of 4 by 4 mm2 tissue
      areas were recorded in transmission mode by a FTIR imaging spectrometer coupled
      to a focal plane array detector. Unsupervised cluster analysis revealed variances
      within each cryosection. Selected clusters of five IR images with known diagnoses
      trained a supervised classification model based on the algorithm soft independent
      modeling of class analogies (SIMCA). This model was applied to distinguish normal
      brain tissue from brain metastases and to identify the primary tumor of brain
      metastases in 15 independent IR images. All specimens were assigned to the
      correct tissue class. This proof-of-concept study demonstrates that IR
      spectroscopy can complement established methods such as histopathology or
      immunohistochemistry for diagnosis.

PMID- 16787639
TI  - Ala-504 is a determinant of substrate binding affinity in the mouse
      Na(+)/dicarboxylate cotransporter.
AB  - The Na(+)/dicarboxylate cotransporters from mouse (mNaDC1) and rabbit (rbNaDC1)
      differ in their ability to handle adipate, a six-carbon terminal dicarboxylic
      acid. The mNaDC1 and rbNaDC1 amino acid sequences are 75% identical. The rbNaDC1
      does not transport adipate and only succinate produced inward currents under two
      electrode voltage clamp. In contrast, oocytes expressing mNaDC1 had adipate
      dependent inward currents that were about 60% of those induced by succinate. In
      order to identify domains involved in adipate transport, we examined the
      functional properties of a series of chimeric transporters made between mouse and
      rabbit NaDC1. We find that multiple transmembrane helices (TM), particularly TM
      8, 9, and 10, are involved in adipate transport. In TM 10 there is only one amino
      acid difference between the two proteins, corresponding to Ala-504 in mouse and
      Ser-512 in rabbit NaDC1. The mNaDC1-A504S mutant had decreased adipate-dependent
      currents relative to succinate-dependent currents and an increase in the K(0.5)
      for both succinate and glutarate. We conclude that multiple amino acids from TM
      8, 9 and 10 contribute to the transport of adipate in NaDC1. Furthermore, Ala-504
      in TM 10 is an important determinant of K(0.5) for both adipate and succinate.

PMID- 16787640
TI  - Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis
      and polymorphonuclear infiltration in traumatic focal brain injury.
AB  - The purpose of this study was to compare the relative effects of mannitol and
      hypertonic saline (HTS) on calpain activity, apoptosis and neuroinflammatory
      response induced by experimental cortical contusion. Four groups of 5 Sprague
      Dawley male rats were submitted to focal brain injury produced by exposing the
      parietal cortex to dynamic cortical deformation. Groups were defined by
      rescucitation fluids administered 30 min post-injury as follows: group 1-0.9%
      normal saline 2 ml/kg; group 2-mannitol 20% 0.5 g/kg; group 3-HTS 2 ml/kg; group
      4-HTS 4 ml/kg. At 72 h, animals were sacrificed. Paraffin-mounted sections of
      were stained for mu-Calpain, TUNEL, active caspase 3 and myeloperoxidase. There
      was no difference in the lesion size between the different groups. In contrast,
      there was a significant reduction in calpain and apoptosis activity and in the
      neuroinflammatory response in animals receiving HTS. Although mannitol proved to
      significantly decrease the neuroinflammatory response and calpain activity, it
      did not affect apoptosis, and its effect was significantly less than that of HTS.
      Importantly, the effect of HTS was mostly independent from the infused volume.
      Our results show that HTS promotes cell survival and reduces secondary brain
      damage following TBI. This protective effect was evidenced at rather small
      infused volumes, proved to encompass several cellular and molecular mechanisms
      involved in secondary cell death and could not be related to relief of
      intracranial pressure. These findings suggest that the high osmolality of HTS may
      have protective effects besides its impact on brain edema.

PMID- 16787641
TI  - p44/42 MAP kinase and c-Jun N-terminal kinase contribute to the up-regulation of
      caspase-3 in manganese-induced apoptosis in PC12 cells.
AB  - Caspase-3 (32 kDa) is one of the primary protease executioners of apoptosis and
      is activated by intra-chain proteolytic cleavage, which generates a large subunit
      (17 kDa) and a small subunit (12 kDa). Typically, after apoptotic stimuli, the
      level of cleaved caspase-3 increases while that of caspase-3 decreases. It has
      been shown that caspase-3 mRNA levels increase in cortex following traumatic
      brain injury or focal ischemia. In the present study, we demonstrate that both
      caspase-3 mRNA and protein increase in apoptotic PC12 cells following exposure to
      manganese which strongly induces caspase-3 cleavage. Up-regulation of caspase-3
      protein was evident in manganese-treated PC12 cells and was moderate in cisplatin
      , rotenone- and A23187-treated cells but was not observed in serum deprivation-,
      anisomycin-, camptothecin-, cycloheximide- or staurosporine-treated cells in
      which all treatments induced extensive DNA fragmentation. Manganese-induced up
      regulation of caspase-3 mRNA was partially attenuated by the pretreatment with
      the MEK inhibitor U0126, but not with the c-Jun N-terminal kinase (JNK) inhibitor
      SP600125. In contrast, the increase in caspase-3 protein was suppressed by both
      U0126 and SP600125. These results suggest that p44/42 MAPK contributes to the up
      regulation of caspase-3 mRNA and the JNK pathway regulates caspase-3 protein
      levels posttranslationally in manganese-induced apoptosis in PC12 cells.

PMID- 16787642
TI  - Membrane excitability of wing and rod cells in frog taste discs following
      denervation.
AB  - The frog tongue has a disc-shaped taste organ (taste disc) on the top of
      fungiform papillae. The taste disc contains two types of cells, wing cells with a
      sheet-like apical process and rod cells with a rod-like apical process. Both wing
      and rod cells can produce action potentials. Unlike the taste buds of mammals,
      frog taste discs do not degenerate over a long period after denervation. Here we
      report that the shapes of wing and rod cells isolated from taste discs in the
      bullfrog (Rana catesbeiana) remained unchanged 1 month after cutting bilateral
      glossopharyngeal nerves. By applying the whole cell patch-clamp technique to
      isolated wing and rod cells, we found voltage-dependent inward currents and
      outward currents and action potentials in denervated frogs as seen in normal
      frogs. These results suggest that the maintenance of morphological integrity and
      electrical excitability of taste cells does not require a nerve supply in frogs.

PMID- 16787643
TI  - Detection of EBV and HPV in nasopharyngeal carcinoma by in situ hybridization.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia
      and is frequently associated with Epstein-Barr virus (EBV). Human papilloma virus
      (HPV) is an epitheliotrophic oncogenic virus that has been detected in a variety
      of head and neck tumors including NPC. This retrospective study was undertaken to
      investigate the prevalence of EBV and HPV infection subtypes 6/11 and 16/18 in 20
      patients with NPC. METHODS: In situ hybridization for EBV-encoded RNA (EBER) and
      tyramid signal amplification of ISH for HPV DNA subtypes 6/11 and 16/18 was
      performed to evaluate the prevalence of EBV and HPV latency infection among
      Iranian Patients with NPC. RESULTS: 16 cases were classified as WHO type III
      (undifferentiated carcinoma) and 4 as WHO type II (non-keratinizing SCC). EBER
      ISH was positive in 19 (95%) of NPCs evaluated and in one metastases from
      cervical primary, included in this series. Two of 20 NPC (10%) contained HPV 6/11
      sequences and two of 20 NPC (10%) contained HPV 16/18 sequences, and combined EBV
      and HPV infection was detected in 3 of the 20 (15%) patients. CONCLUSION: Our
      data indicated that EBV is closely associated with NPC in Iran. In addition, a
      low percentage of EBV positive NPC contained HPV sequences. The significance of
      coexistence of EBV and HPV in NPC requires further study.

PMID- 16787644
TI  - Atrial natriuretic peptide inhibits osmotical glial cell swelling in the ischemic
      rat retina: dependence on glutamatergic-purinergic signaling.
AB  - Atrial natriuretic peptide (ANP) is a regulator of the water and electrolyte
      content in the brain which also mediates cell volume homeostasis. Here, we
      determined whether the expression of ANP in the retina of the rat undergoes
      changes during ischemia-reperfusion, and whether ANP affects the osmotic swelling
      of Muller glial cells in postischemic retinas under hypotonic conditions.
      Transient retinal ischemia was induced by elevation of the intraocular pressure
      above systolic blood pressure for 1h. At 1 and 3 days after reperfusion, there
      was an increased content of ANP protein in the retina, as determined by Western
      blotting. The increase of the retinal ANP content was markedly reduced when
      triamcinolone acetonide (10 mM in 2 microl vehicle) was intravitreally injected
      before ischemia. ANP inhibited the osmotic swelling of Muller cell somata in
      retinal slices. The effect of ANP was mediated by activation of NP receptors
      expressed by retinal neurons which evoked a release of glutamate. The stimulation
      of metabotropic glutamate receptors expressed by Muller cells evoked an autocrine
      purinergic signaling mechanism that resulted in the opening of K(+) and Cl(-)
      channels; the ion efflux counteracted the osmotic swelling of Muller cells. It is
      concluded that the expression of ANP is transiently upregulated in the
      postischemic retina of the rat. The increased expression of ANP may represent a
      part of the retinal response to transient ischemia and may inhibit cytotoxic
      glial cell swelling.

PMID- 16787645
TI  - Rapid progression of carotid lesions in HAART-treated HIV-1 patients.
AB  - To obtain data on the evolution of carotid lesions, we evaluated 133 patients at
      their first antiretroviral regimen, followed for at least 2 years; 77 treated
      with protease inhibitors (PIs): Group A and 56 with non-nucleosidic reverse
      transcriptase inhibitors (NNRTIs): Group B. All patients were subjected to
      carotid ultrasonography. In Group A, among the previously normal patients 22.5%
      developed lesions, 40% remained normal, 37.5% shifted to other antiretroviral
      regimens. Among the 37 previously pathologic patients, 46% worsened, 19% were
      stable, in 8% the lesions had disappeared, 27% shifted. In Group B, among the
      previously normal patients, 12.7% developed lesions, 80.8% remained unaltered,
      6.5% shifted. Among the previously pathologic patients, 12.5% worsened, lesions
      reversed in 25%, remained stable in 50% and 12.5% shifted to PI. At statistical
      analysis, in Group A both the percentage of patients developing new lesions and
      the percentage of patients who worsened was significantly higher. In conclusion,
      we evidenced a more rapid onset of lesions in patients treated with PIs with
      respect to patients treated with NNRTIs and towards a more rapid evolution of the
      previous lesions. The shift from PIs to NNRTI/3 NRTI seems related to a lower
      rate of evolution. Interestingly, a disappearance of lesions was detected in both
      groups.

PMID- 16787646
TI  - Characterisation of progenitor cells in human atherosclerotic vessels.
AB  - Recent data from animal models has demonstrated that both endothelial and smooth
      muscle progenitor cells contribute to the development of atherosclerosis.
      However, no data exists concerning the presence of progenitor cells in human
      atherosclerotic vessels. In the present study, a range of normal and
      atherosclerotic human arteries were collected from patients undergoing coronary
      artery bypass surgery. Segments of internal mammary artery (normal controls), and
      segments of proximal ascending aorta with visible fatty streak were analysed.
      Immunofluorescence was used to detect a panel of progenitor cell markers. A small
      number of progenitor cells were identified within neointimal lesions and the
      adventitia with variable expression of CD34, stem cell antigen (Sca-1), c-kit and
      VEGF receptor 2 (VEGFR2) markers, but no CD133 expression. On average there was a
      two- to three-fold increase in progenitor cell number in the adventitia of
      atherosclerotic vessels compared with normal controls, with a significant
      difference (p<0.05) in the frequency of cells expressing VEGFR2. Thus, we have
      provided the first evidence that vascular progenitor cells exist within
      atherosclerotic lesions, and identified an increased number of progenitor cells
      in the adventitia of human atherosclerotic vessels. These cells might be a source
      for smooth muscle cells (SMCs), macrophages and endothelial cells (ECs) that form
      atherosclerotic lesions.

PMID- 16787647
TI  - Use of oral corticosteroids and the risk of acute myocardial infarction.
AB  - INTRODUCTION: A few epidemiological studies suggested an increased coronary heart
      disease (CHD) risk with high doses of oral corticosteroids. METHODS: We performed
      a cohort study with nested case-control analysis to estimate the risk of acute
      myocardial infarction (AMI) associated with the use of oral corticosteroids by
      dose and duration. We followed-up 404,183 persons, 50-84 years old, without
      cancer from the general UK population. After validation of a random sample
      (confirmation rate of 96%), we included 4795 hospitalised cases of AMI or CHD
      deaths. We randomly sampled 20,000 controls, frequency matched by sex, age and
      calendar year. Relative risks were estimated using unconditional logistic
      regression. RESULTS: The adjusted OR for AMI in current users of oral
      corticosteroids compared to non-users was 1.42 (95% CI: 1.17-1.72). The risk
      during the first 30 days of use (OR=2.24; 95% CI: 1.56-3.20) was greater than
      with longer duration (OR=1.22; 95% CI 0.98-1.52). The risk was more pronounced
      (OR=2.15; 95% CI 1.45-3.14) among users of prednisolone equivalent doses
      >10mg/day. The dose effect was observed both among patients with and without CHD
      or COPD/asthma. CONCLUSION: These results suggest a small increased risk of AMI
      with oral corticosteroid use with a greater risk observed among users of high
      corticosteroid dose.

PMID- 16787649
TI  - Can CXCL16 be linked to coronary vascular disease? Comment on the article by
      Sheikine et al.

PMID- 16787650
TI  - Can the theory of gradient liquid chromatography be useful in solving practical
      problems?
AB  - Advances in the theory of gradient liquid chromatography and their practical
      impacts are reviewed. Theoretical models describing retention in reversed-phase,
      normal-phase and ion-exchange modes are compared. Main attention is focused on
      practically useful models described by two- or three-parameter equations fitting
      the experimental data in the range of mobile phase composition utilized for
      sample migration during gradient elution. The applications of theory for gradient
      method development, optimization and transfer are addressed. The origins and
      possibilities for overcoming possible pitfalls are discussed, including the
      effects of the instrumental dwell volume, uptake of mobile phase components on
      the column and size of the sample molecules. Special attention is focused on
      gradient separations of large molecules.

PMID- 16787648
TI  - High interleukin-6 plasma levels are associated with low HDL-C levels in
      community-dwelling older adults: the InChianti study.
AB  - BACKGROUND: Low levels of high density lipoprotein cholesterol (HDL-C) are
      associated with increased incidence of coronary heart disease (CHD). A better
      understanding of the mechanisms leading to low HDL-C and CHD is essential for
      planning treatment strategies. Clinical studies have demonstrated that cytokines
      might affect both concentration and composition of plasma lipoproteins, including
      HDLs. METHODS: We investigated the possible association between low HDL-C levels,
      defined as < or =10th gender specific percentile, and circulating markers of
      inflammation (IL-1beta, TNF-alpha, IL-6, IL-10, IL-18, and CRP) in a population
      of 1044 community dwelling older Italian subjects from the InChianti study.
      RESULTS: Using logistic regression analysis we demonstrated that IL-6 levels (III
      versus I tertile, OR: 2.10; 1.10-3.75), TG (III versus I tertile OR: 27.45; 8.47
      88.93), fasting insulin (III versus I tertile OR: 2.84; 1.50-5.42), and age (OR:
      1.038; 1.002-1.075) were associated with low HDL-C independent of smoking, BMI,
      waist circumference, hypertension, diabetes, physical activity, alcohol intake,
      oral hypoglycaemics, CRP, IL-18, and TNF-alpha levels. The adjusted attributable
      risk of low HDL-C in the exposed group (III tertile of IL-6) was 54%.
      CONCLUSIONS: The present study provides the epidemiological evidence that besides
      triglycerides, fasting insulin, and age, IL-6 is one of the main correlates of
      low HDL-C levels in older individuals.

PMID- 16787651
TI  - Extraction of rotenone from Derris elliptica and Derris malaccensis by
      pressurized liquid extraction compared with maceration.
AB  - The extraction of active compounds from plants is one of the most critical steps
      in the commercial development of natural products for medicinal, herbicidal or
      pesticidal use. The focus of this study was to compare conventional maceration
      and pressurized liquid extraction (PLE) techniques for the efficient extraction
      of rotenone from the stem and root of Derris elliptica Benth and Derris
      malaccensis Prain. The effects of experimental variables, such as solvent,
      temperature and pressure, on PLE efficiency have been studied. Chloroform was
      determined to be a good extraction solvent (rotenone content 40.6%, w/w) compared
      to commonly used solvent, 95% ethanol (rotenone content 15.0%, w/w). The optimal
      conditions for PLE were 50 degrees C and 2000 psi. PLE showed higher extraction
      efficiency (rotenone content 46.1%, w/w) as compared with conventional maceration
      method (rotenone content 40.6%, w/w). The order of rotenone content found in
      crude extract obtained by optimized method from the highest to the lowest was
      root (46.1%, w/w) and stem (9.4%, w/w) of D. elliptica and stem of D. malaccensis
      (5.2%, w/w), respectively. Moreover, the results from this study indicated that
      PLE was considerably less time and solvent consuming (30 min, 3 ml/g of dried
      sample) than the conventional maceration techniques (72 h, 10 ml/g of dried
      sample).

PMID- 16787652
TI  - Identification of a cardiac isoform of the murine calcium channel alpha1C (Cav1.2
      a) subunit and its preferential binding with the beta2 subunit.
AB  - We describe a cardiac muscle isoform of the voltage-dependent calcium channel
      alpha1 subunit, which corresponds to the rabbit ortholog of alpha1C-a (Cav1.2a).
      We also cloned smooth muscle isoforms alpha1C-b (Cav1.2b) and alpha1C-d
      (Cav1.2d). Differences among these three isoforms lie within the N-terminal
      region (exon 1A or 1B), the sixth transmembrane segment of domain I (exon 8A or
      8B), and the use of exon 10, which forms the intracellular loop between
      transmembrane domains I and II. Two-hybrid analysis revealed interactions among
      the three alpha1 isoforms and beta subunits. In vitro overlay and
      immunoprecipitation analyses revealed preferential binding between alpha1C-a and
      beta2, which is also expressed at a high level in the heart.

PMID- 16787654
TI  - Hippocampal volume reduction in 22q11.2 deletion syndrome.
AB  - Hippocampal volume reduction and decreased memory skills form a characteristic
      neurofunctional alteration observed in schizophrenia. Individuals affected with
      22q11.2 deletion syndrome (22q11DS), while exhibiting memory deficits throughout
      development, are also at high risk for developing schizophrenia. The present
      study sought to investigate hippocampal volume reduction as separate of global
      grey matter reduction in a large, independent sample of individuals with 22q11DS.
      Volumetric data from structural magnetic resonance imaging was obtained for 43
      individuals affected with 22q11DS, aged 6-39 years of age, as well as for 40
      healthy individuals matched for age and gender. Drawing of the amygdala was
      included to enhance the delineation of the hippocampus, and circumscription of
      both the amygdala and the hippocampus were executed using an increased resolution
      matrix. After controlling for total grey volume reductions observed in affected
      individuals, a significant decrease in hippocampus volume was observed in the
      22q11DS group, driven by significant bilateral volumetric reduction of the body
      of the hippocampus. These results are discussed in reference to memory and
      cerebral alterations already reported in 22q11DS. Further, the specific
      implications of hippocampus body volume reduction are outlined in light of its
      anatomical relationships and its function in memory. Finally, reduction of
      hippocampal volume in 22q11DS is examined in the context of psychiatric risk
      status associated to the deletion.

PMID- 16787653
TI  - Translocation of a tRNA with an extended anticodon through the ribosome.
AB  - Coordinated translocation of the tRNA-mRNA complex by the ribosome occurs in a
      precise, stepwise movement corresponding to a distance of three nucleotides along
      the mRNA. Frameshift suppressor tRNAs generally contain an extra nucleotide in
      the anticodon loop and they subvert the normal mechanisms used by the ribosome
      for frame maintenance. The mechanism by which suppressor tRNAs traverse the
      ribosome during translocation is poorly understood. Here, we demonstrate
      translocation of a tRNA by four nucleotides from the A site to the P site, and
      from the P site to the E site. We show that translocation of a punctuated mRNA is
      possible with an extra, unpaired nucleotide between codons. Interestingly, the
      NMR structure of the four nucleotide anticodon stem-loop reveals a conformation
      different from the canonical tRNA structure. Flexibility within the loop may
      allow conformational adjustment upon A site binding and for interacting with the
      four nucleotide codon in order to shift the mRNA reading frame.

PMID- 16787655
TI  - Integration of feeding and spontaneous physical activity: role for orexin.
AB  - Spontaneous physical activity is activity that is non-volitional, or
      subconscious, such as fidgeting and shifting in one's seat, and time spent moving
      (standing and ambulating). Recent evidence indicates that spontaneous physical
      activity, and the resulting thermogenesis (non-exercise activity thermogenesis)
      may be regulated by brain systems. A large number of brain areas, with their
      associated neurotransmitter populations and connectivity, participate in the
      regulation of feeding behavior by acting as energy sensing and modulating
      centers. Although less well characterized, it is likely that a multitude of
      neurotransmitters and brain areas act to mediate spontaneous physical activity.
      These two behaviors, feeding and spontaneous physical activity, affect energy
      intake and expenditure and thus are important to body weight. Interestingly,
      often the two behaviors are affected simultaneously; when feeding is affected, so
      too is spontaneous physical activity, and both food intake and physical activity
      (whether spontaneous or volitional) influence activity of brain areas important
      to both. Several brain areas and neuropeptides are important to feeding and
      spontaneous physical activity. The lateral hypothalamus is one area that appears
      important to both behaviors, as stimulation or lesion of this region produces
      alterations in feeding behavior and spontaneous physical activity. Orexin
      neurons, with their central location in the lateral hypothalamus, widespread
      projections and connectivity to other brain areas important to energy
      homeostasis, are well situated to perform an integrative function. This review
      focuses on how hypothalamic orexins participate in both feeding and spontaneous
      physical activity, and provides potential models for the integration of signals
      important to both.

PMID- 16787656
TI  - The spirostenol (22R, 25R)-20alpha-spirost-5-en-3beta-yl hexanoate blocks
      mitochondrial uptake of Abeta in neuronal cells and prevents Abeta-induced
      impairment of mitochondrial function.
AB  - Abeta(1-42) has been shown to uncouple the mitochondrial respiratory chain and
      promote the opening of the membrane permeability transition (MPT) pore, leading
      to cell death. We have previously reported that the spirostenol derivative (22R,
      25R)-20alpha-spirost-5-en-3beta-yl hexanoate (SP-233) protects neuronal cells
      against Abeta(1-42) toxicity by binding to and inactivating the peptide.
      Picomolar concentrations of Abeta(1-42) decreased the mitochondrial respiratory
      coefficient in mitochondria isolated from the rat forebrain, and this decrease
      was partially reversed by SP-233. SP-233 abolished the uncoupling of oxidative
      phosphorylation induced by carbonyl cyanide 3-chlorophenylhydrazone on isolated
      mitochondria. These results are consistent with a direct effect of SP-233 on the
      MPT. Moreover, SP-233 displayed a neuroprotective effect on SK-N-AS human
      neuroblastoma cells treated with the MPT promoter, phenylarsine oxide. Treatment
      of SK-N-AS cells with Abeta(1-42) resulted in an accumulation of the peptide in
      the mitochondrial matrix; SP-233 completely scavenged Abeta(1-42) from the
      matrix. In addition, SP-233 protected the cells against mitochondrial toxins
      targeting complexes IV and V of the respiratory chain. These results indicate
      that Abeta(1-42) and SP-233 exert direct effects on mitochondrial function and SP
      233 protects neuronal cells against Abeta-induced toxicity by targeting Abeta
      directly.

PMID- 16787657
TI  - A systematic review of the impact of work environment on smoking cessation,
      relapse and amount smoked.
AB  - BACKGROUND: Smoking is an important issue for the majority of the world's working
      population. It is important to explore in which ways the workplace might
      contribute to changes in smoking status and smoking behavior. The present article
      provides a systematic review and quality assessment of studies that have
      addressed the impact of factors in the work environment on smoking behavior.
      METHODS: An evaluation of the methodological quality of 22 prospective studies
      was based on 14 explicit criteria, which included features of study design,
      statistical analysis, sampling issues and measurement. The level of scientific
      evidence was evaluated for each study. RESULTS: There was strong evidence for an
      effect of the work environment on the amount smoked, but insufficient or mixed
      evidence regarding cessation and relapse. Summarizing the results, high job
      demands were associated with higher amount smoked and with increased likelihood
      of cessation. Resources at work and social support were positively associated
      with cessation and negatively associated with relapse and the amount smoked.
      CONCLUSIONS: The results supported the overall hypothesis that the work
      environment influences aspects of smoking behavior. Recommendations are made for
      more intervention studies where changes in work environment are carried out in
      combination with health promotion interventions.

PMID- 16787658
TI  - Prolonging bovine sperm-oocyte incubation in modified medium 199 improves embryo
      development rate and the viability of vitrified blastocysts.
AB  - This study was conducted to compare the efficacy of four in vitro fertilization
      (IVF) media: Bracket and Oliphant's medium (BO), modified medium 199 (IVF-M199),
      modified Tyrode's medium (MTM), and modified KSOM (m-KSOM) on fertilization
      efficiency and blastocyst formation rate. In addition, we wanted to investigate
      the benefit of prolonging the IVF period (from 6 to 18 h) using the two most
      effective IVF media determined in our initial experiment; subsequently,
      blastocyst viability was assessed following vitrification. A higher incidence of
      polyspermic fertilization was observed in the MTM (6%) and in BO, in both the 6
      and 18 h (7% and 11%, respectively) groups, than in the m-KSOM (1%) or in the IVF
      M199 6 or 18 h (1 and 3%, respectively) groups. Cleavage rates were similar in
      BO, IVF-M199, and MTM 48 h post-fertilization; however, the lowest cleavage rate
      was observed for m-KSOM. A greater proportion of zygotes developed into 8-cell
      embryos in IVF-M199 than in other IVF media. Subsequently, a greater proportion
      of blastocyst formation and hatching was achieved in IVF-M199 (40% and 79%,
      respectively) or BO (35% and 74%, respectively) than in m-KSOM (18% and 58%,
      respectively) or MTM (22% and 66%, respectively). Prolonging IVF to 18 h did not
      alter cleavage rates; however, the highest rate of overall blastocyst formation
      was achieved in the IVF-M199 18 h (49%), rather than in the BO 18 h (20%) group.
      Vitrified/thawed blastocysts from IVF-M199 groups re-expanded and developed
      better, as compared to the BO 18 h group, and hatching rate and total cell number
      in IVF-M199 18 h group was comparable to the control groups (non-vitrified).
      Vitrification reduced survival compared to controls. In conclusion, IVF-M199 was
      successfully used for IVF, compared favorably to BO medium, and offered the
      advantage of an extended IVF period for up to 18 h that requires only one-half a
      dose of semen, and resulted in better quality blastocysts that endured
      vitrification with a hatching rate comparable to that of control groups.

PMID- 16787659
TI  - Practitioner's guide to pocket pet and rabbit theriogenology.
AB  - This paper provides a review of reproductive characteristics of hamsters, guinea
      pigs, gerbils, hamsters, rats, and mice, as well as rabbits and chinchillas. It
      is not intended to be a source of the facts of reproduction (which can be readily
      found in many references) but rather to highlight some of the unique
      characteristics of the various species and common problems that clients may
      present to theriogenologists. This paper includes information regarding sexing,
      mating, gestation, parturition, lactation, and comments regarding spays and
      neuters.

PMID- 16787660
TI  - Comparative effects of limited tryptic hydrolysis on physicochemical and
      structural features of seed 11S globulins.
AB  - The effect of the limited proteolysis by trypsin on selected seed storage 11S
      globulins (broad bean and pea legumins, glycinin and helianthinin) was studied by
      high-sensitive differential scanning calorimetry, fluorescence spectroscopy and
      analysis of proteolysis kinetics. Different behaviour of glycinin and
      helianthinin, on one hand, and broad bean and pea legumins, on the other, were
      observed: in the first group changes in the physicochemical characteristics of
      the proteins due to their limited proteolysis are more pronounced in comparison
      with the second one, in relation with the extent of primary structure
      modifications. The differences observed have been evaluated in relation with the
      amino acid sequence features of the four 11S globulin studied and agree with the
      literature data concerning the protein structural changes in the course of the
      limited proteolysis.

PMID- 16787661
TI  - Rheological properties of concentrated aqueous injectable calcium phosphate
      cement slurry.
AB  - In this paper, the steady and dynamic rheological properties of concentrated
      aqueous injectable calcium phosphate cement (CPC) slurry were investigated. The
      results indicate that the concentrated aqueous injectable CPC showed both plastic
      and thixotropic behavior. As the setting process progressed, the yield stress of
      CPC slurry was raised, the area of the thixotropic hysteresis loop was enlarged,
      indicating that the strength of the net structure of the slurry had increased.
      The results of dynamic rheological behavior indicate that the slurry presented
      the structure similar to viscoelastic body and the property of shear thinning at
      the beginning. During the setting process, the slurry was transformed from a
      flocculent structure to a net structure, and the strength increased. Different
      factors had diverse effects on the rheological properties of the CPC slurry in
      the setting process, a reflection of the flowing properties (or injection), and
      the microstructure development of this concentrated suspension. Raising the
      powder-to-liquid ratio decreased the distance among the particles, increased the
      initial strength, and shortened the setting time. In addition, raising the
      temperature improved the initial strength, increased the order of reaction, and
      shortened the setting time, which was favorable to the setting process. The
      particle size of the raw material had much to do with the strength of original
      structure and setting time. The storage module G' of CPC slurry during the
      setting process followed the rule of power law function G'=A exp(Bt), which could
      be applied to forecast the setting time, and the calculated results thereafter
      are in agreement with the experimental data.

PMID- 16787662
TI  - The spectrum of myelodysplastic syndromes post-solid organ transplantation: a
      single institutional experience.
AB  - An increased incidence of acute myeloid leukemia (AML) has recently been
      documented in patients post-solid organ transplantation but the incidence and
      types of myelodysplastic syndromes (MDS) occurring in this patient population are
      not known. We identified 5 patients (3M, 2F, age 48-64 years) who developed MDS
      ranging from 1.8 to 25 years (median 4.2 years) post-solid organ transplantation,
      only 2 patients had received azathioprine. The cumulative incidence of MDS in
      heart and lung transplant recipients at 15 years was 0.5% and 1.8%, respectively,
      which is markedly higher compared to the general population. Low-risk types of
      MDS predominated, 3 of 5 patients are alive (median 3.9 years) since diagnosis.
      Deletions of chromosome 20q, which have not been previously reported in post
      transplant MDS/AML, were identified in 3 cases. Our findings expand the
      morphologic and cytogenetic spectrum of MDS occurring post-solid organ
      transplantation and suggest that mechanisms beside azathioprine toxicity might be
      important in disease pathogenesis.

PMID- 16787663
TI  - Potent inhibition of the CD4-dependent T cell response by J2, a novel nonpeptide
      organic ligand of CD4 D1.
AB  - The interaction between CD4 and major histocompatibility complex (MHC) class II
      proteins is critical for the activation of CD4+ T cells, which are involved in
      transplantation reactions and a number of autoimmune diseases. It is known that
      the CD4 N-terminal immunoglobulin variable region-like domain (D1) is directed
      toward and reaching into the two membrane-proximal domains of the MHC class II
      molecule. Thus, compounds targeted to D1 would be expected to function as the
      inhibitors of the interaction of CD4 and class II MHC molecules. In this study,
      we used a computer-based design method to screen thousands of non-peptidic
      compounds in a molecular database and identified a group of compounds as
      potential ligands of CD4 D1. These small organic compounds were then synthesized
      and tested by actual biological assays. One of them, named J2, which possessed
      favorable activity, was obtained. Experimental data showed that J2 could
      specifically block stable CD4-MHC class II binding and elicit significant
      inhibition of immune responses in vitro and in vivo. All the results demonstrated
      the therapeutic potential of this compound as a novel immunosuppressive agent.

PMID- 16787665
TI  - Cytoarchitectonic organization of the entorhinal cortex of the canine brain.
AB  - The present study describes the cytoarchitectonic and chemoarchitectonic
      organization of the canine entorhinal cortex (EC). We distinguished medial,
      laterodorsal, and latero-intermediate subdivisions based on the organization of
      cortical layers using Nissl and Timm staining and AChE histochemistry. The medial
      subdivision is located at the border of the parasubiculum and is characterized by
      a narrow cortex, wide layer II, and densely packed cells in layer V. At its
      caudal extent, distinct spherical groups of small cells are situated at the
      border of layer I/II. The laterodorsal subdivision is located along the rhinal
      sulcus and borders area 35 of the perirhinal cortex. Its cortex is wide and
      layers tend to merge. Layer II of the laterodorsal subdivision contains scattered
      "stellate" cells, which are not organized into islands. The latero-intermediate
      subdivision displays a complex layer organization. The most easily distinguished
      is layer II, which is comprised of two main cell populations; "stellate" neurons
      arranged into "islands" and small, round cells distributed within and below the
      stellate cells. Layer III contains sparse cells that are arranged into vertical
      clusters, whereas layer IV (lamina dissecans) is especially wide. Nine fields,
      named according to their rostral to caudal position, were distinguished based on
      further analyses of layer differentiation. The main features of the rostrocaudal
      differentiation are a gradual disappearance of "island" organization in layer II,
      increasing cortical thickness, and wider layers containing small and more densely
      packed cells. Cytoarchitectonic differentiation was determined by observation of
      specific histochemical patterns of AChE- and Timm-stained sections.

PMID- 16787666
TI  - Methods for isolating highly-enriched embryonic spinal cord neurons: a comparison
      between enzymatic and mechanical dissociations.
AB  - Spinal cord neuronal culture is a useful system to study normal and abnormal
      functions of the spinal cord. For many bioassays, obtaining large quantities of
      highly purified spinal cord neurons is required. However, technical difficulties
      exist in obtaining these cells reliably and consistently. By comparing two
      dissociation methods, mechanical and enzymatic dissociations, we found that the
      enzymatic dissociation of embryonic day 14-15 spinal cords resulted in
      significantly higher cell yield than the mechanical dissociation (25.40 +/- 5.41
      x 10(6) versus 3.43 +/- 0.52 x 10(6) cells per 12 embryos; n = 6/group; p <
      0.01). Furthermore, cell viability was significantly higher after the enzymatic
      than the mechanical dissociation (83.40 +/- 3.08% versus 32.81 +/- 3.49%, n =
      4/group; p < 0.01). In both methods, highly purified populations of primary
      neurons were obtained (mechanical: 85.17 +/- 2.84%; enzymatic: 87.67 +/- 2.52%; n
      = 3/group). Critical measures that affect culture outcomes include, but not
      limited to, the age of embryo, cell seeding density, dissociation time, and
      elimination of non-neuronal cells. Thus, the present study has identified the
      enzymatic dissociation method to be a preferred method for obtaining large
      quantity of highly-enriched embryonic spinal cord neurons.

PMID- 16787668
TI  - Cold pressor test as a marker for the detection of early stage coronary
      atherosclerosis.

PMID- 16787667
TI  - Is HIV drug resistance a limiting factor in the development of anti-HIV NNRTI and
      NRTI-based vaginal microbicide strategies?
AB  - Antiviral drugs that act at specific sites within the HIV life cycle have
      important rationale for development as anti-HIV microbicides. However, to be
      effective, such drugs must act by directly interfering with viral enzymatic
      function and eliminate the ability of HIV to mediate infection. Compounds that
      are developed as microbicides must have high potency, and should ideally not be
      well absorbed from the vaginal cavity in order to minimize any potential problems
      of drug resistance. Such compounds should also be active over long periods of
      time and should be able to be combined with other active agents, in order to
      promote the concept of synergy, such as that which has been demonstrated in HIV
      therapeutic studies.

PMID- 16787669
TI  - Coronary calcification mimicking the stent: analysis by MDCT Plaque Map.

PMID- 16787670
TI  - Differences in inflammatory and thrombotic markers between unstable angina and
      acute myocardial infarction.
AB  - BACKGROUND: Unstable coronary syndromes are characterised by increased
      inflammatory process and endothelial activation. However, the underlying
      mechanisms of the acute coronary syndromes are still obscure. We evaluated the
      differences of inflammatory and thrombotic markers, at the acute phase of
      unstable angina (UA) and acute myocardial infarction (AMI). METHODS: The
      population of the study consisted of 216 subjects: 136 patients with UA, 57
      patients with AMI and 23 healthy controls. Blood samples were taken by their
      admission to the hospital. Inflammatory and thrombotic markers were measured by
      ELISA. RESULTS: Patients with UA had significantly higher levels of interleukin-6
      (IL-6), soluble vascular cells adhesion molecule (sVCAM-1) and von Willebrand
      factor (vWF) (p<0.05 vs controls), and lower levels of antithrombin III (ATIII)
      (p<0.01 vs controls) and protein C (PrtC) (p<0.05 vs controls). Similarly,
      patients with AMI had higher levels of IL-6, sVCAM-1, vWF and tissue plasminogen
      activator (tPA) (p<0.01 vs controls) and lower levels of ATIII (p<0.01 vs
      controls) and prtC (p<005 vs controls). Patients with AMI had significantly
      higher levels of vWF, tPA and sVCAM-1 compared to UA patients (p<0.05).
      CONCLUSIONS: Patients with unstable coronary syndromes had increased levels of IL
      6, sVCAM-1 and vWF as well as decreased levels of ATIII and PrtC by their
      admission. However, patients with AMI had higher levels of all the endothelium
      derived inflammatory (e.g. sVCAM-1) of thrombotic/fibrinolytic (e.g. tPA and vWF)
      markers, compared to those with UA. These findings imply that patients with
      myocardial infarction show further increase of endothelium-derived inflammatory
      and thrombotic markers compared to patients with unstable angina, in response to
      a similar proinflammatory stimuli.

PMID- 16787671
TI  - Hypoglycemia-induced myocardial infarction: an unusual adverse effect of
      sulfonylureas.
AB  - Hypoglycemia is a significant problem of sulfonylureas treated diabetes. Although
      attention has focused on its neurologic consequence, the possibility of
      cardiovascular side effects should also be considered. A 77-year-old man
      presented with hypoglycemia-induced myocardial infarction with sulfonylureas
      therapy. We wish to report this unusual adverse effect of sulfonylureas and
      provide some reference for the clinicians who treat similar cases.

PMID- 16787672
TI  - Difficult atrial septal defect closure: intracardiac echocardiographic
      visualization of an unexpected caveat.

PMID- 16787664
TI  - Maternal infection and white matter toxicity.
AB  - Studies examining maternal infection as a risk factor for neurological disorders
      in the offspring have suggested that altered maternal immune status during
      pregnancy can be considered as an adverse event in prenatal development.
      Infection occurring in the mother during the gestational period has been
      implicated in multiple neurological effects. The current manuscript will consider
      the issue of immune/inflammatory conditions during prenatal development where
      adverse outcomes have been linked to maternal systemic infection. The discussions
      will focus primary on white matter and oligodendrocytes as they have been
      identified as target processes. This white matter damage occurs in very early
      preterm infants and in various other human diseases currently being examined for
      a linkage to maternal or early developmental immune status. The intent is to draw
      attention to the impact of altered immune status during pregnancy on the
      offspring for the consideration of such contributing factors to the general
      assessment of developmental neurotoxicology.

PMID- 16787673
TI  - Plaque sealing: are the benefits outweighing the risks?
AB  - A 36-year-old man was admitted with reported short attacks of acute chest pain
      with small increment of troponin and CK-MB and normal ECG. The 64-slice CT
      coronary angiography revealed a large non-obstructing non-calcified plaque in the
      proximal left anterior descending artery with positive vessel remodeling. The
      conventional coronary angiogram was normal but the intravascular ultrasound
      confirmed the CT findings. A drug eluting stent was implanted to seal the plaque.
      During the procedure, myocardial damage had occurred. At 6-month follow-up, 64
      slice CT revealed minimal in-stent hyperplasia, which was confirmed at
      conventional angiography.

PMID- 16787674
TI  - A preliminary passive surveillance of clinical diseases of cart pulling camels in
      Faisalabad metropolis (Pakistan).
AB  - We identified clinical disorders of all 200 city-dwelling cart pulling male
      camels attending the Veterinary Teaching Hospital, University of Agriculture,
      Faisalabad, Pakistan during a 7-year period (1993-1999). Data were collected
      prospectively on a predesigned form and collated. Diagnoses of different
      diseases/disorders were based on clinical examination supplemented with relevant
      laboratory tests. A total of 463 entries of 34 different clinical
      diseases/disorders were recorded. Sarcoptic mange (35% of 200 camels) followed by
      anhidrosis (23%) and trypanosomosis (19%) were the three most frequently
      encountered disorders. The body system most often involved was the integument
      (31%) followed by gastrointestinal (21%), locomotory (12%), thermoregulatory
      (6%), blood (6%), urogenital (6%), lymphatic (3%), nervous (3%), respiratory (3%)
      and ocular (3%).

PMID- 16787675
TI  - Monensin might protect Ontario, Canada dairy cows from paratuberculosis milk
      ELISA positivity.
AB  - Our objective was to define the role of monensin sodium in protecting cows from
      being milk-ELISA positive for paratuberculosis in Ontario, Canada dairy herds. In
      total, 4933 dairy cows from 94 herds were enrolled in this cross-sectional study.
      Forty-four of the enrolled herds were selected purposively by their herd
      veterinarian and another 50 herds were randomly selected from a local milk
      production-recording agency. A herd-management survey was completed on each farm
      during the months of May through August 2003. During this same time-period,
      composite milk samples were collected from all lactating cows and tested with a
      milk-ELISA for antibodies to Mycobacterium avium subspecies paratuberculosis.
      Analyses were stratified according to the paratuberculosis history of the herds.
      In the 48 herds in which paratuberculosis had not been diagnosed before, the use
      of calf hutches and monensin in milking cows were both associated with reduced
      odds of a cow testing positive (OR=0.19 and 0.21, respectively). In the 46 herds
      with a prior history of paratuberculosis, feeding monensin to the breeding-age
      heifers was associated with decreased odds of a cow testing positive (OR=0.54).
      Monensin use might be associated with milk-ELISA positivity, but its impact on
      the transmission of paratuberculosis remains unknown.

PMID- 16787676
TI  - Cattle transfers between herds under paratuberculosis surveillance in The
      Netherlands are not random.
AB  - The rate and structure of cattle transfers between 206 Dutch cattle herds with a
      'Mycobacterium avium subsp. paratuberculosis (Map)-free' status by November 2002,
      were analyzed over a 3-year period (November 1999-November 2002). Of the 206 'Map
      free' herds, 184 were closed herds during the period studied. In total, 280
      cattle had been introduced into 22 herds at an average rate of 0.33 animals per
      year per 100 cattle present in the 206 herds. Assuming a random herd-contact
      structure, the observed rate of cattle transfers between certified 'Map-free'
      herds was sufficiently low to relax the surveillance scheme to biennial herd
      examinations by pooled fecal culture of all cattle > or =2 years of age. The
      cattle transfers were not randomly distributed over the herds. Forty-four of the
      280 cattle originated from 12 other 'Map-free' herds. The other 236 cattle did
      not originate from a 'Map-free' herd and were introduced into a herd before it
      obtained the 'Map-free' status. No cattle were introduced into any of the 'Map
      free' herds from which cattle were transferred to other 'Map-free' herds. Thus,
      continued propagation of the infection by cattle transfers was impossible in the
      group of herds studied during the study period. Therefore the surveillance scheme
      may be further relaxed, and may be differentiated regarding the risk herds pose
      to other herds.

PMID- 16787677
TI  - Direct trapping of formaldehyde formed via oxidative N-demethylation of N,N
      dialkylarylamines by Bacillus megaterium using cysteamine derivatization.
AB  - Oxidative N-demethylation was measured by incubation experiments using Bacillus
      megaterium isolated from topsoil as a biocatalyst for the N-demethylation of the
      N,N-dialkylarylamines N,N-dimethylaniline and N-ethyl-N-methylaniline. Formed
      formaldehyde, normally difficult to analyse in biological systems because of
      further metabolization, was successfully trapped and converted into thiazolidine
      by addition of cysteamine into the incubation media. Studies using N,N-di
      (trideutero-methyl)-aniline and N-ethyl-N-(trideuteromethyl)-aniline as well as
      N,N-di-[methyl-(13)C]-aniline and N-ethyl-N-[methyl-(13)C]-aniline were performed
      to confirm that the N-demethylation proceeds via formaldehyde.

PMID- 16787678
TI  - Role of proteins in resistance mechanism of Pseudomonas fluorescens against heavy
      metal induced stress with proteomics approach.
AB  - The genus Pseudomonas is a group of gram-negative, motile, rod-shaped bacteria
      known for their metabolic versatility. One of the species is Pseudomonas
      fluorescens, which has an efficient system for detoxification of industrial
      waste. Other aspects include, catabolic versatility, excellent root colonizing
      abilities and capacity to produce a wide range of antifungal metabolites. They
      are also known for their resistance and survival in the presence of several
      organic and inorganic pollutants. P. fluorescens has also been isolated from
      metal polluted water and soils but the elucidation of proteins responsible for
      its survival is still not clear. The aim of the study was to elucidate the
      differential protein expression of this bacterium when exposed to heavy metal
      stress, using two-dimensional electrophoresis. The proteins spo VG and enolase
      showed upregulation during the bacterial exposure to lead and copper.
      Hypothetical protein showed downregulation when bacterium was exposed to cobalt.
      Some proteins like xylosyltransferase, ORF 18 phage phi KZ, OMP H1 and
      translational elongation factor EF-Tu appeared only during their exposure to
      cobalt. These were absent in the control condition. Analysis of the
      differentially expressed proteins as well as the newly synthesized proteins along
      with the results obtained growth and enzyme activity indicate the involvement of
      all these factors in the survival of this organism in the presence of heavy
      metals.

PMID- 16787679
TI  - Microsphere-integrated collagen scaffolds for tissue engineering: effect of
      microsphere formulation and scaffold properties on protein release kinetics.
AB  - A promising approach to control the time and space distribution of signalling
      molecules inside tissue engineering scaffolds consists in entrapping
      biodegradable microspheres releasing the protein locally for long time frames.
      However, a rational design of microsphere-integrated scaffolds requires the
      knowledge of protein release profiles directly within the polymeric template. In
      this work, PLGA microspheres encapsulating rhodamine-labelled bovine serum
      albumin (BSA-Rhod) as a model protein were produced in different formulation
      conditions and tested for their release features in solution and in collagen and
      collagen/hyaluronic acid (HA) scaffolds. BSA-Rhod release profiles from single
      microspheres in solution and within the scaffold were assessed by using a
      confocal laser scanning microscopy (CLSM)-assisted method. Results suggest that
      the same diffusion-erosion process controls BSA-Rhod release from microspheres in
      solution and collagen. Nonetheless, two main factors contribute protein release
      within the scaffold, that is water activity in the release environment and
      transport properties of the protein in the gel. While microsphere formulation
      mainly controls the induction time necessary to activate protein release, polymer
      scaffold composition governs the release rate. Thus, the fine regulation of a
      tissue engineering construct may be obtained by an appropriate combination of
      microspheres and scaffolds, providing a spatial and temporal control over
      signalling molecule delivery.

PMID- 16787680
TI  - Nitric oxide as treatment for an emerging epidemic of obesity-related
      glomerulopathy.

PMID- 16787681
TI  - Physical therapy management of low back pain has changed.
AB  - BACKGROUND: Since the 1990s, new insights in the physical therapy management of
      low back pain have been described in guidelines. Furthermore, insurance companies
      introduced a volume policy to control the costs for physical therapy. OBJECTIVE:
      This study aims to establish if developments in knowledge and health policy since
      the 1990s have resulted in changes in the physical therapy management of patients
      with low back pain (LBP) in the Netherlands. METHODS: Data from 3148 patients,
      referred because of LBP, were selected from the databases of two registration
      studies (1989-1992 and 2002-2003) of patients treated by physical therapists.
      Descriptive statistics were used to compare patient characteristics. A multi
      level regression analysis was carried out to determine a change in the number of
      treatment sessions adjusting for patient and disease characteristics, and to
      control for different levels (patient and physical therapist). RESULTS: A small
      decline in the number of treatment sessions was observed. In 2002, exercise
      therapy was the most frequently applied intervention, while massage and physical
      modalities were the interventions of first choice in the early 1990s. CONCLUSION:
      Our results suggest that since 1990 the management of patients with LBP by
      physical therapists in the Netherlands has changed. Both quality management by
      the profession and volume policy by government and insurance companies seem to
      have been instrumental in bringing about a decline in the number of treatment
      visits and an increase in the use of evidence-based interventions.

PMID- 16787682
TI  - Gene amplification in cancer.
AB  - Gene amplification is a copy number increase of a restricted region of a
      chromosome arm. It is prevalent in some tumors and is associated with
      overexpression of the amplified gene(s). Amplified DNA can be organized as
      extrachromosomal elements, as repeated units at a single locus or scattered
      throughout the genome. Common chromosomal fragile sites, defects in DNA
      replication or telomere dysfunction might promote amplification. Some regions of
      amplification are complex, yet elements of the pattern are reproduced in
      different tumor types. A genetic basis for amplification is suggested by its
      relative frequency in some tumor subtypes, and its occurrence in "early"
      preneoplastic lesions. Clinically, amplification has prognostic and diagnostic
      usefulness, and is a mechanism of acquired drug resistance.

PMID- 16787683
TI  - Pulmonary artery reconstruction by a custom-made heterologous pericardial conduit
      in the treatment of lung cancer.
AB  - Lung cancer may involve the pulmonary artery (PA) either by direct extension of
      the primary tumor or by invasion of the hilar lymph nodes. In these instances, a
      radical resection is usually a pneumonectomy despite distal functioning lung
      tissue. To spare the lung parenchyma, angioplastic procedures requiring removal
      of a portion of the arterial wall or a circumferential resection with arterial
      reconstruction have been used. Several techniques of pulmonary arterioplasty have
      been explored suggesting that the incidence of postoperative complications is
      acceptably low and long-term local control can be achieved. Over a period of 7
      years, 84 angioplastic procedures (alone or associated with bronchoplasty) were
      performed at our institution. Partial PA resection was performed in 80 (95.2%)
      patients. Reconstruction was performed by running suture in 63 (75%) patients and
      using a pericardial patch in 17 (20.2%) cases (16 autologous and 1 heterologous).
      A complete PA resection and reconstruction was performed in four (4.8%) patients
      by a polytetrafluoroethylene (PTFE) prosthesis (n=2) and by a custom-made bovine
      pericardial conduit (n=2). The latter are the topic of this report.

PMID- 16787684
TI  - Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with
      limited stage small cell lung cancer.
AB  - A few series in the literature were published before 1987 on syndrome of
      inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer
      (SCLC). This study examines the outcome in more recent era. From 1981-1998, there
      were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244
      were of limited stage (LS). A chart review and statistical analyses were
      performed using Mann-Whitney test, chi-square test and Kaplan-Meier method.
      Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of
      230 LS patients without SIADH. There were more patients with poorer performance
      status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex,
      age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior
      vena cava obstruction, performance status, weight loss, and lactic dehydrogenase
      at presentation, were comparable between the two groups. Treatments given, e.g.,
      extent of surgical resection (if performed, whether complete/incomplete), total
      number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The
      response to chemo-radiation was not significantly different (P=0.7). Five-year
      overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus
      20%, P=0.13) showed that group A patients had a worse outcome, though of
      borderline significance. Symptoms related to SIADH included: weakness, 4
      patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The
      range of lowest sodium level was 110-129. Two patients also had paraneoplastic
      myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among
      the 14 patients who initially presented with SIADH and recurred later, 10 had
      recurrence of SIADH at the time of tumor recurrence. Serum sodium was useful for
      post-treatment surveillance in SCLC patients who presented with SIADH, with 71%
      (10/14) developing SIADH again at the time of recurrence. SIADH is a poor
      prognostic factor for LS SCLC.

PMID- 16787685
TI  - Synchronous multiple primary lung cancers with different response to gefitinib.
AB  - Synchronous bronchiolo-alveolar cell carcinoma (BAC) in both lungs and squamous
      cell carcinoma in left lung were found in a 66-year-old male smoker. After two
      courses of chemotherapy with gemcitabine and carboplatin, the left lung mass had
      partially resolved, however, the extent of BAC had been increased. When gefitinib
      was used as a second-line chemotherapy, the consolidation lesions of BAC was
      improved while the mass of squamous cell carcinoma was aggravated. The analysis
      of epidermal growth factor receptor-tyrosine kinase (EGFR-TK) mutations showed
      that BAC had the deletion, delE746-A750 in exon 19, however, squamous cell
      carcinoma had no mutations. These synchronous tumors with different location,
      histology, status of EGFR-TK mutations and response to chemotherapy might be
      caused by different molecular pathogenesis.

PMID- 16787686
TI  - Dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide
      given on days 1 and 8 in patients with advanced non-small cell lung cancer.
AB  - This is a dose-finding study of fixed dose gemcitabine and escalating doses of
      ifosfamide, in chemo naive patients with advanced non-small cell lung cancer. The
      purpose of the study was to determine the optimal dosage and the maximal
      tolerated dose (MTD) of a specified schedule of gemcitabine and ifosfamide.
      Patients received gemcitabine 1250 mg/m2 and ifosfamide between 1.6 and 2.2 g/m2,
      intravenously, on days 1 and 8, repeated every 3 weeks for a maximum of four
      cycles. RESULTS: Sixteen patients entered the study. Three patients were entered
      at the first dose level of ifosfamide (1.6 g/m2) and none experienced any dose
      limiting (DLT) toxicity. In dose level 2 (1.8 g/m2), two patients had grade IV
      haematological toxicities, but they reached 21 days without any other dose
      limiting toxicity (DLT). Three further patients entered at this level but they
      were withdrawn due to disease progression. The sixth patient entered without any
      DLT. Three patients entered dose level 3 (2.0 g/m2), without any grade IV
      toxicity. The first patient entered into dose level 4 (2.2 g/m2), had progressive
      disease within 21 days and was withdrawn and another three were entered and had
      no DLT during the first 21 days. Four (33%) of the patients had stable disease
      and 67% had progressive disease. CONCLUSION: The MTD of the ifosfamide
      gemcitabine combination was not reached in the present study, as no DLT was
      observed. This combination at the dose levels of this protocol has little or no
      activity in patients with advanced NSCLC.

PMID- 16787688
TI  - Urinary oxytocin as a non-invasive biomarker for neurohypophyseal hormone
      secretion.
AB  - The objective was to characterize the urinary oxytocin (OT) system with the goal
      of using it as a biomarker for neurohypophyseal peptide secretion. We studied
      urinary OT secretion in mice under three conditions: (1) in OT gene deletion mice
      (OT -/-) which lack the ability to produce the peptide; (2) after arterial
      vascular infusion of OT and (3) after physiological stimulation with consumption
      of 2% sodium chloride. OT was measured by radioimmunoassay (RIA) and Surface
      Enhanced Laser Desorption Ionization Time of Flight Mass Spectroscopy (SELDI TOF
      MS). In OT -/- mice (n=25), urinary OT levels were not detectable, while in OT
      +/+ mice (n=23) levels were 250.2+/-35.3 pg/ml. To evaluate blood/urine transfer,
      mice with chronic carotid arterial catheters were infused with saline or OT (5 or
      20 pmol/min). Peak urine OT levels were 89+/-11.5 and 844+/-181 ng/ml in the low
      and high OT groups, respectively. Proteomic evaluation showed MS peaks,
      corresponding to OT ( approximately 1009 Da) and a related peptide (
      approximately 1030 Da) with highest levels in mice infused with OT. Salt loading
      (5 days of 2% NaCl as drinking water) increased plasma osmolality (3.3%),
      increased plasma and urinary vasopressin (AVP), but caused no changes in OT.
      Thus, using non-invasive urine samples, we document that urinary OT and AVP can
      be used to monitor changes in peptide secretion. Urinary OT and AVP, as well as
      other urinary peptides, may provide a viable biomarker for peptide secretion and
      may be useful in clinical studies.

PMID- 16787687
TI  - Effect of chemotherapy for advanced non-small cell lung cancer on patients'
      quality of life. A randomized controlled trial.
AB  - BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) do not have
      curative treatment options; therefore, treatments should prolong survival and
      improve quality of life (QoL). We compared the effect on QoL of two docetaxel
      platinum regimens with vinorelbine-cisplatin. METHODS: QoL was assessed by the
      Lung Cancer Symptom Scale (LCSS) and the general EuroQol five-dimensional
      questionnaire (EQ-5D) in 926 chemotherapy-naive patients with stages IIIB to IV
      NSCLC. Patients were randomly assigned to receive: docetaxel 75 mg/m2 plus
      cisplatin 75 mg/m2, every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin 6
      mg/ml min, every 3 weeks (DCb); or vinorelbine 25 mg/m2/week plus cisplatin 100
      mg/m2, every 4 weeks (VC). RESULTS: Overall, patients treated with either
      docetaxel-containing regimen had better QoL than VC-treated patients (LCSS global
      item "QoL today": P=0.064 for DC and P=0.016 for DCb versus VC; EQ-5D global item
      "health state today": P=0.016 for DC and P<0.001 for DCb versus VC). DC-treated
      patients experienced improved pain relief compared with VC (P=0.033), whereas
      pain relief with DCb and VC was similar. Patients treated with either docetaxel
      regimen had more favorable changes in performance status (P=0.065 for DC and
      P<0.001 for DCb versus VC) and mean weight loss (0.06 kg, gain of 0.08 kg, and
      2.27 kg for DC, DCb, and VC, respectively; P<0.001 for both DC versus VC and DCb
      versus VC). CONCLUSION: The TAX 326 study shows that docetaxel-platinum regimens
      relieve symptoms and improve QoL in patients with advanced NSCLC. DCb and DC were
      superior to VC in all QoL outcomes assessed except for the difference between DC
      and VC in LCSS "QoL today", which was not significant.

PMID- 16787689
TI  - Non-destructive pollution exposure assessment in the European hedgehog (Erinaceus
      europaeus): IV. Hair versus soil analysis in exposure and risk assessment of
      organochlorine compounds.
AB  - Few ecotoxicological studies on mammals use non-destructive methodologies,
      despite the growing ethical concern over the use of destructive sampling methods.
      In the present study we assessed exposure of hedgehogs (Erinaceus europaeus) to
      polychlorinated biphenyls (PCBs), dichloro-diphenyl-trichloroethanes (DDTs),
      hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB), by investigating
      concentrations of these compounds in soils and hedgehog hair from seven study
      sites around the urban area of Antwerp, Belgium. No relationships were observed
      between organochlorine compound concentrations in soils and hair from the
      different study areas. Furthermore, the individual variation of contamination
      levels in hair within study sites was high, especially for HCHs and HCB, and hair
      and soil had different relative profiles for PCBs, DDTs and HCHs. Our results
      show that concentrations of organochlorine compounds in soils alone are not
      predictive of the risk of these pollutants to hedgehogs and that tissue analyses
      are preferred to soil analyses in exposure and risk assessment studies.

PMID- 16787690
TI  - PAH-concentrations and compositions in the top 2 cm of forest soils along a 120
      km long transect through agricultural areas, forests and the city of Oslo,
      Norway.
AB  - The top 2 cm of forest soils were collected along a 120 km long south-north
      transect running through Norway's largest city Oslo. Forty samples were analysed
      for their polycyclic aromatic hydrocarbon (PAH(16) as defined by the U.S.
      Environmental Protection Agency) concentrations and compositions. Local
      variations in the PAH values are high and the reported concentrations are in
      general low (maximum sumPAH16: 2.6 mg/kg). The transect shows distinct
      differences of sumPAH16 values from south to north. PAH concentrations are
      substantially lower in the less populated areas at the north end of the transect
      than at the urbanised and much more populated south end. Several high values
      occur in a forested area to the north of Oslo, used for recreation purposes. The
      PAH distribution patterns point towards a predominantly pyrogenic origin. Local
      Cambrian carbon-rich black shales can be excluded as sources for PAHs in the
      forest soils.

PMID- 16787692
TI  - Activation of different pathways of apoptosis by air pollution particulate matter
      (PM2.5) in human epithelial lung cells (L132) in culture.
AB  - Epidemiological studies have associated the increase of respiratory and
      cardiovascular mortality and morbidity with high levels of air pollution
      particulate matter (PM). However, the underlying mechanisms of actions by which
      PM induce adverse health effects are still unclear. We have recently undertaken
      an extensive investigation of the adverse health effects of air pollution
      PM(2.5), and shown that in vitro short-term exposure to PM(2.5) induced oxidative
      stress and inflammation in human lung epithelial cells (L132). Hence, it was
      convenient to complete the physical and chemical characterization of PM and to
      investigate whether in vitro short-term exposure to PM could be imply in the
      activation of apoptosis. Accordingly, we found that 92.15% of PM were equal or
      smaller than 2.5 microm and their specific surface area was 1m(2)/g. Inorganic
      (i.e. Fe, Al, Ca, Na, K, Mg, Pb, etc.) and organic (i.e. polycyclic aromatic
      hydrocarbons) chemicals were found in PM, suggesting that much of them derived
      from wind-borne dust from the industrial complex and the heavy motor vehicle
      traffic. In other respects, we showed that PM exposure induced apoptosis by
      activating not only the tumor necrosis factor-alpha (TNF-alpha)-induced pathway
      (i.e. TNF-alpha secretion, caspase-8 and -3 activation), but also the
      mitochondrial pathway (i.e. 8-hydroxy-2'-desoxyguanosine formation, cytochrome c
      release from mitochondria, caspase-9 and -3 activation). Moreover, changes in the
      transcription rates of p53, bcl-2, and bax genes, on the one hand, and DNA
      fragmentation, on the other hand, were reported in PM-exposed proliferating L132
      cells, revealing the occurrence of apoptotic events. Taken together, these
      findings suggested that in vitro short-term exposure to PM(2.5) induced apoptosis
      in L132 cells.

PMID- 16787693
TI  - Chlorpyrifos induces apoptosis in human monocyte cell line U937.
AB  - In order to investigate chlorpyrifos-induced cell death and its underlying
      mechanism in human immune cells, a human monocyte like cell line (U937) was
      treated with chlorpyrifos at 4.45-570microM for 0.5-24h at 37 degrees Celsius in
      a 5% CO(2) incubator. We first found that chlorpyrifos induced cell death of U937
      in a dose- and time-dependent manner, as shown by LDH and MTT assays and PI
      uptake. Then, we investigated if chlorpyrifos-induced cell death consisted of
      apoptosis, as determined by analysis of Annexin-V staining and the intracellular
      level of active caspase-3 by flow cytometry, and DNA fragmentation analysis. We
      found that chlorpyrifos induced apoptosis in U937 in a time- and dose-dependent
      manner, as shown by Annexin-V staining. DNA fragmentation was detected when cells
      were treated with 71 to 284microM chlorpyrifos for 4 or 6h. Chlorpyrifos also
      induced an increase of intracellular active caspase-3 in U937 cells in a dose
      dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited
      the chlorpyrifos-induced apoptosis. These findings indicate that chlorpyrifos can
      induce apoptosis in U937 cells, and this effect is partially mediated by
      activation of intracellular caspase-3.

PMID- 16787694
TI  - Successful management of pregnancy-associated severe aplastic anemia.

PMID- 16787695
TI  - Simple enucleation for the treatment of PT1a renal cell carcinoma: our 20-year
      experience.
AB  - OBJECTIVES: To evaluate the safety and efficacy of simple enucleation as a
      conservative treatment for pT1a RCC, and to report on the incidence of major
      complications, local recurrence, and progression-free and disease-specific
      survival rates. METHODS: We retrospectively reviewed the data of 232 patients who
      had nephron-sparing surgery (NSS) by simple enucleation between 1986 and 2004 for
      sporadic, unilateral, pathologically confirmed pT1a RCC. The patients' status was
      evaluated last in September 2005. The mean (median, range) follow-up was 76 (61,
      12-225) months. RESULTS: The mean (SD, median, range) tumor greatest dimension
      was 2.8 (0.78, 2.85, 0.6-4) cm. The histopathologic review according to the
      International Union Against Cancer and American Joint Commission for Cancer
      (1997) classification revealed 198 clear cell (85.3%), 18 papillary (7.8%), 15
      chromophobe (6.5%) and one (0.4%) collecting duct RCCs. There were no major
      complications, such as prolonged acute tubular necrosis/chronic renal
      insufficiency and bleeding requiring open reoperation. One patient developed
      postoperative late retroperitoneal fluid collection consistent with urinoma,
      which required aspiration, drainage position and JJ stenting for 3 weeks. The 5-
      and 10-year cancer-specific survival were 96.7% and 94.7%, respectively. The 5-
      and 10-year progression-free survival were 96% and 94%, respectively. Overall, 13
      (6.4%) patients had disease progression, three of whom had local recurrences
      alone (1.5%) elsewhere in the kidney; none had local recurrence at the level of
      the enucleation bed. CONCLUSIONS: Simple tumor enucleation is a safe and
      acceptable nephron-sparing treatment that provides excellent long-term local
      control and cancer-specific survival rates.

PMID- 16787696
TI  - A brief review of the addition of gonadotropin-releasing hormone agonists (GnRH
      Ag) to growth hormone (GH) treatment of children with idiopathic growth hormone
      deficiency: Previously published studies from America.
AB  - Despite aggressive, early and continuous growth hormone (GH) treatment of
      children with idiopathic (I) growth hormone deficiency (GHD), height outcomes are
      often below -1 SDS and do not achieve mid-parental height targets. As pubertal
      growth accounts for 15% of total growth and gonadotropin-releasing hormone
      agonist (GnRH-Ag) therapy has successfully prolonged the "prepubertal" growth
      phase in central precocious puberty, the addition of GnRH-Ag to GH in IGHD has
      been widely utilized to try to enhance linear growth. Results in the two large GH
      registry databases and GH prediction models do not support the success of such
      treatment, although several smaller, controlled trials do indicate some value.
      Whether GnRH-Ag therapy could be more successful if its use were related to the
      tempo or age of onset of puberty in a specific child is not known. No universally
      agreed guidelines exist for the use of GnRH-Ag plus GH in children with GHD or
      other short stature syndromes and may still be considered experimental.

PMID- 16787697
TI  - Management of short stature with GnRH agonist and co-treatment with growth
      hormone: a controversial issue.
AB  - Adolescent growth is the focus of several interventions aimed at increasing the
      amplitude of the adolescent spurt. Favorable results with GnRH agonists in
      precocious puberty have encouraged attempts to increase the duration of the
      adolescent growth spurt by delaying normal puberty in short individuals using
      GnRH agonists with or without growth hormone. These approaches remain highly
      controversial, have not been validated and approved for use by regulatory
      authorities and were the topic of a session at the 6th International Conference
      on the Onset of Puberty. Here we review the available information on the efficacy
      and safety of this approach. GnRH agonists, when used outside the context of
      precocious puberty, induce a modest gain when used for extended periods of time.
      Several trials have now shown that growth hormone alone can modestly increase
      adult height in short adolescents with idiopathic short stature or in those born
      small for gestational age. The association of growth hormone and GnRH agonists
      still lacks a definite demonstration of its additional efficacy and available
      results do not allow firm conclusions. In conclusion, watchful waiting or sex
      steroids in delayed puberty are generally the best options in short children
      presenting around puberty. However, long-term and adequately powered clinical
      trials, focusing on efficacy, safety and clinical significance are needed to
      fully evaluate the combination of growth hormone and GnRH agonists in short
      adolescents. In the meanwhile, these approaches should be considered as
      experimental.

PMID- 16787698
TI  - The effect of different propolis harvest methods on its lead contents determined
      by ET AAS and UV-visS.
AB  - Argentinean propolis is exported to different countries, specially Japan. The
      market demands propolis quality control according to international standards. The
      analytical determination of some metals, as lead in food, is very important for
      their high toxicity even in low concentrations and because of their harmful
      effects on health. Flavonoids, the main bioactive compounds of propolis, tend to
      chelate metals as lead, which becomes one of the main polluting agents of
      propolis. The lead found in propolis may come from the atmosphere or it may be
      incorporated in the harvest, extraction and processing methods. The aim of this
      work is to evaluate lead level on Argentinean propolis determined by
      electrothermal atomic absorption spectrometry (ET AAS) and UV-vis
      spectrophotometry (UV-visS) methods, as well as the effect of harvest methods on
      those contents. A randomized test with three different treatments of collection
      was made to evaluate the effect of harvest methods. These procedures were:
      separating wedges (traditional), netting plastic meshes and stamping out plastic
      meshes. By means of the analysis of variance technique for multiple comparisons
      (ANOVA) it was possible to conclude that there are significant differences
      between scraped and mesh methods (stamped out and mosquito netting meshes). The
      results obtained in the present test would allow us to conclude that mesh methods
      are more advisable than scraped ones in order to obtain innocuous and safe
      propolis with minor lead contents. A statistical comparison of lead determination
      by both, ET AAS and UV-visS methods, demonstrated that there is not a significant
      difference in the results achieved with the two analytical techniques employed.

PMID- 16787699
TI  - Stabilization/solidification of hazardous and radioactive wastes with alkali
      activated cements.
AB  - This paper reviews progresses on the use of alkali-activated cements for
      stabilization/solidification of hazardous and radioactive wastes. Alkali
      activated cements consist of an alkaline activator and cementing components, such
      as blast furnace slag, coal fly ash, phosphorus slag, steel slag, metakaolin,
      etc., or a combination of two or more of them. Properly designed alkali-activated
      cements can exhibit both higher early and later strengths than conventional
      portland cement. The main hydration product of alkali-activated cements is
      calcium silicate hydrate (CSH) with low Ca/Si ratios or aluminosilicate gel at
      room temperature; CSH, tobmorite, xonotlite and/or zeolites under hydrothermal
      condition, no metastable crystalline compounds such as Ca(OH)(2) and calcium
      sulphoaluminates exist. Alkali-activated cements also exhibit excellent
      resistance to corrosive environments. The leachability of contaminants from
      alkali-activated cement stabilized hazardous and radioactive wastes is lower than
      that from hardened portland cement stabilized wastes. From all these aspects, it
      is concluded that alkali-activated cements are better matrix for
      solidification/stabilization of hazardous and radioactive wastes than Portland
      cement.

PMID- 16787700
TI  - Decolourization of azo dyes using magnesium-palladium system.
AB  - Magnesium-palladium system was found to efficiently decolourize reactive black 5,
      sunset yellow FCF and tartrazine dyes. There is complete loss of visible range
      absorption peaks and extent of colour removal exceeded 95% within 24 h of
      reaction. There is appearance of new peak(s) in the UV region and/or gradual and
      significant shift of the lambda(max) in the UV range during 1-24 h of reaction of
      dyes with Mg/Pd system. LC-MS analyses following the reaction of dyes with
      magnesium palladium system suggest reductive cleavage of azo bonds and formation
      of amines as the end products. Kinetic analyses of dye decolourization indicate
      that the reaction follows first order kinetics. Agreement between the
      experimental and predicted Michaelis-Menten plots for the decolourization of
      reactive black 5, sunset yellow FCF and tartrazine dyes by Mg(0)/Pd(4+) system,
      suggests the correctness of Michaelis-Menten model for the prediction of dye
      decolourization rates by Mg(0)/Pd(4+) system. Our investigations reveal that
      Mg(0)/K(2)PdCl(6) system is more effective in decolourizing dyes as compared to
      Mg(0)/Pd(0)-alumina or Mg(0) alone. Results obtained from reuse experiments
      suggest that Pd(0) pellets have the potential for recycling which will make the
      treatment process cost effective. Mg(0)/Pd(4+) system was found to be efficient
      in decolourizing mixture of drimarene, remazol and procion dyes as well as raw
      effluent generated by textile dye manufacturing company.

PMID- 16787701
TI  - Reaction paths and efficiency of photocatalysis on TiO2 and of H2O2 photolysis in
      the degradation of 2-chlorophenol.
AB  - The kinetics of 2-chlorophenol (2-CP) degradation and mineralization in the
      aqueous phase was investigated under irradiation at 254 nm, employing either
      photocatalysis in the presence of titanium dioxide, or hydrogen peroxide
      photolysis, to compare the efficiency of these photoinduced advanced oxidation
      techniques. Photocatalysis under 315-400 nm wavelength irradiation was also
      investigated. The concentration versus time profiles of the degradation
      intermediates catechol, chloro- and hydroxy-hydroquinone allowed the
      identification of the reaction paths prevailing under the different experimental
      conditions. Efficient CCl bond cleavage occurred as a consequence of direct light
      absorption by 2-CP, while hydroxyl radicals, photogenerated at the water
      photocatalyst interface or during H(2)O(2) photolysis, were the main oxidation
      agents, able to attack both 2-CP and its degradation intermediates. Highest
      degradation and mineralization efficiencies were achieved under H(2)O(2)
      photolysis at 254 nm.

PMID- 16787702
TI  - Physical and environmental properties of asphalt mixtures containing incinerator
      bottom ash.
AB  - This paper presents parts of the results from a research project sponsored by
      Taiwan Environmental Protection Administration (TEPA), investigating both the
      physical and environmental properties of asphalt mixtures using different amount
      of incinerator bottom ash (IBA) as fine aggregate substitution. The Marshall mix
      design method was used to determine the design asphalt content and evaluate the
      potential performance of these IBA-asphalt mixtures. Water sensitivity and wheel
      track rutting were also performed on these mixtures. Leachates, from both
      laboratory and outdoor leaching tests, were performed to measure the
      concentration of selected heavy metals and the level of daphnia toxicity. While
      with adequate Marshall stability, the IBA-asphalt mixtures were shown to have
      excessively high Marshall flow and excessively low VMA (voids in the mineral
      aggregate). The results of the wheel tracking tests also indicated that the IBA
      asphalt mixtures had low rutting resistance. The results of the water sensitivity
      test according to procedure of AASHTO T283 method showed that the IBA-asphalt
      mixtures had a higher tensile strength ratio (TSR) as compared with the
      conventional asphalt mixtures. Considering the environmental aspects, outdoor
      leaching tests showed that IBA had a high level of daphnia toxicity. From an
      ecological perspective, IBA could be identified as hazardous waste in Taiwan.
      However, after being mixed with asphalt binder, the concentration of heavy metals
      and the levels of daphnia toxicity were significantly reduced. The leachates of
      10-day flat plate leaching tests on Marshall specimens containing IBA indicated
      that the heavy metal were undetectable and the daphnia toxicity was ineffective.

PMID- 16787703
TI  - Comparisons of levels of polychlorinated dibenzo-p-dioxins/dibenzofurans in the
      surrounding environment and workplace of two municipal solid waste incinerators.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the surrounding
      environment (outdoor) and workplace air of two municipal solid waste incinerators
      (MSWIs, T and M) were characterized and compared. T and M represented two typical
      municipal solid waste incinerators in the north of Taiwan, which have different
      processes for controlling the PCDD/F emissions. The results of this study are
      summarized as follows. (1) The total PCDD/F and the total PCDD/F WHO-TEQ
      concentrations in the workplace air were 5-13 and 5-15 times higher than those in
      the outdoor air, respectively. Obviously, it is worthwhile to explore more on
      health risk assessment for exposure of PCDD/Fs emitted from MSWIs, particularly
      in the workplace air. (2) Mean total PCDD/F I-TEQ concentrations in the outdoor
      air ranged between 0.0216 and 0.155 pg I-TEQ/Nm(3) and averaged 0.0783 pg I
      TEQ/Nm(3) (0.0828 pg WHO-TEQ/Nm(3)) during two seasons for two MSWIs, which were
      6.5-fold higher than that of a remote site (0.0119 pg I-TEQ/Nm(3) or 0.0132 pg
      WHO-TEQ/Nm(3)) in Taiwan. However, the above outdoor air concentration levels in
      the MSWIs were still much lower than the air quality limitation of PCDD/Fs (0.6
      pg I-TEQ/Nm(3)) in Japan []. (3) PCDFs were the primary toxicity distributors for
      PCDD/Fs in the outdoor air, since the ratios of PCDDs/PCDFs (I-TEQ) at all
      sampling sites ranged from 0.180 to 0.492 and were less than unity. (4) The OCDD,
      OCDF, 1,2,3,4,6,7,8-HpCDD and 1,2,3,4,6,7,8-HpCDF were the four dominant species
      in both workplace and outdoor air near MSWIs. (5) By spraying water on and
      wetting both the fly and bottom ashes, the mean total PCDD/F I-TEQ concentration
      in the workplace air was reduced 86.9% in the T MSWI. The above results indicate
      an appropriate improving action did inhibit the fugitive emission of PCDD/Fs and
      reduce the health risk of workers during work handling ashes in MSWIs.

PMID- 16787704
TI  - Ozone direct oxidation kinetics of Cationic Red X-GRL in aqueous solution.
AB  - This study characterizes the ozonation of the azo dye Cationic Red X-GRL in the
      presence of TBA (tert-butyl alcohol), a scavenger of hydroxyl radical, in a
      bubble column reactor. Effects of oxygen flow rate, temperature, initial dye
      concentration, and pH were investigated through a series of batch tests.
      Generally, enhancing oxygen flow rate enhanced the removal of dye. However, there
      was a minimum removal of dye at temperature 298 K. Increasing or decreasing
      temperature enhanced the degradation of dye. Increasing the initial dye
      concentration decreased the removal of dye while the ozonation rate increased.
      The rate constants and the kinetic regime of the reaction between ozone and dye
      were obtained by fitting the experimental data to a kinetics model based on a
      second order overall reaction, first order with respect to both ozone and dye.
      The Hatta numbers of the reactions were between 0.039 and 0.083, which indicated
      that the reaction occurred in the liquid bulk. The direct oxidation rate constant
      k(D) was correlated with temperature by a modified Arrhenius Equation with an
      activation energy E(a) of 15.538 kJ mol(-1).

PMID- 16787705
TI  - Use of biosurfactant to remediate phenanthrene-contaminated soil by the combined
      solubilization-biodegradation process.
AB  - The applicability of the combined solubilization-biodegradation process was
      examined using soil-packed column. In the solubilization step, 50 pore volumes of
      150 mg/l biosurfactants solution was injected and the percentage removal of
      phenanthrene (mg) was 17.3% and 9.5% from soil with pH 5 and 7, respectively. The
      highest solubility was detected at pH 5 and this result confirmed that adjusting
      the pH of the biosurfactants solution injected could enhance the solubility of
      phenanthrene. Following this, soil samples were completely transferred to batches
      and incubated for 10 weeks to monitor phenanthrene degradation. The phenanthrene
      concentration in the soil samples decreased significantly during the
      biodegradation step in all soil samples, except for the soil sample that was
      flushed with biosurfactants solution with pH 4. This indicated that the
      degradation of contaminants by specific species might not be affected by the
      residual biosurfactants following application of the solubilization process.
      Moreover, these results suggested that the biosurfactant-enhanced flushing
      process could be developed as a useful technology with no negative effects on
      subsurface environments and could be combined with the biodegradation process to
      increase the removal efficiency.

PMID- 16787706
TI  - Association study of the INPP1, 5HTT, BDNF, AP-2beta and GSK-3beta GENE variants
      and restrospectively scored response to lithium prophylaxis in bipolar disorder.
AB  - In the present study we investigated the influence of a series variants in genes
      (the serotonin transporter, glycogen synthase kinase-3beta, inositol
      polyphosphatase 1-phosphate, brain-derived neurotrophic factor and activator
      protein 2beta) related to the action of lithium carbonate, a drug used for
      prophylaxis in mood disorders. We used a sample of unrelated patients with
      bipolar disorder type I on lithium therapy for at least 2 years who met the
      proposed response criteria for prophylactic response. Of the 134 patients, 61
      patients were considered full responders, 49 non-responders and 24 partial
      responders. No significant differences were observed for the genotype or allele
      frequencies for good, partial and poor responders for the five gene variants: for
      BDNF G196A (genotype: chi2 = 3.67, 4 d.f., p = 0.45; allele: chi2 = 2.31, 2 d.f.,
      p = 0.31); for INPP1 C973A (genotype: chi2 = 1.35, 4 d.f., p = 0.85; allele: chi2
      = 0.04, 2 d.f., p = 0.98); for AP-2beta [CAAA](4/5) (genotype: chi2 = 3.18; 4
      d.f., p = 0.52; allele: chi2 = 0.92, 2 d.f., p = 0.063); for 5HTTLPR (genotype:
      chi2 = 0.67, 4 d.f., p = 0.96; allele: chi2 = 0.27, 2 d.f., p = 0.87); for GSK
      3beta A-1727T (genotype: chi2 = 3.55, 4 d.f., p = 0.47; allele: chi2 = 0.48, 2
      d.f., p = 0.78). These investigated variants are not predictive factors for
      lithium prophylactic response in our sample of bipolar disorder type I patients.
      However, it is still possible that a subgroup of a diverse ethnic ancestry may be
      predisposing to some of those variants for lithium response.

PMID- 16787707
TI  - Candidate gene analysis of IP-10 gene in patients with Alzheimer's disease.
AB  - Interferon-gamma-inducible Protein-10 (IP-10) is supposed to play a role in
      Alzheimer's disease (AD) development, as demonstrated by increased levels in
      cerebrospinal fluid from patients with AD. A mutation scanning of IP-10 exonic
      region was carried out in 10 patients with AD and 10 age-matched controls,
      demonstrating the presence of two previously reported single nucleotide
      polymorphisms (SNPs) in exon 4 (G-->C and T-->C) as well as a novel SNP in exon 2
      (C-->T). Exon 4 G-->C and T-->C allelic variants were next evaluated in a
      population of 279 AD patients and 251 controls, in order to determine whether
      their presence could influence the susceptibility towards the development of the
      disease. These two SNPs were in complete linkage disequilibrium. No differences
      in haplotype frequencies were found in AD patients as compared with controls,
      even stratifying according to the presence of Apolipoprotein E varepsilon4
      allele, gender or age at onset. A new protocol was developed to easily determine
      the C-->T SNP in exon 2. A preliminary analysis revealed a very low frequency of
      this allelic variant (1%). Therefore, the complete association study was not
      carried out because the size of our population was not sufficient to draw
      reliable conclusions. According to these results, IP-10 does not seem to be a
      risk factor for AD. However, a novel rare polymorphism has been identified, which
      could exert a role in AD susceptibility. Thus, further studies on larger
      populations are needed before confidently excluding IP-10 as a susceptibility
      gene for AD.

PMID- 16787709
TI  - Immunoneutralization of gonadotropin-releasing hormone type-III suppresses male
      reproductive behavior of cichlids.
AB  - To investigate the roles of gonadotropin-releasing hormone (GnRH) types in
      reproductive behaviors, antisera against GnRH1, GnRH2 and GnRH3 were
      stereotaxically administered into the intracerebroventricular region to
      neutralize the three native GnRH types in the brain of male tilapia Oreochromis
      niloticus. Reproductive behaviors (nest-building and aggressive behaviors), and
      morphological changes of the three GnRH systems were investigated by
      immunocytochemistry. GnRH1, GnRH2 and GnRH3 immunoreactive fibers were
      significantly decreased following injections of GnRH antisera indicating
      successful neutralization of their respective endogenous GnRH peptides. GnRH1-
      and GnRH2-immunoneutralization did not inhibit reproductive behaviors but GnRH3
      immunoneutralization significantly decreased nest-building ability (Saline: 26.5
      +/- 3.7%/day versus GnRH3: 6.1 +/- 2.9%/day, P < 0.001), nest size (Saline: 0.67
      +/- 0.09 points versus GnRH3: 0.10 +/- 0.05 points, P < 0.0002) and aggressive
      behavior (Saline: 2.34 +/- 0.19 points versus GnRH3 1.06 +/- 0.12 points, P <
      0.0001). These observations provide evidence that GnRH3 is a potent
      neuromodulator of reproductive behaviors in male tilapia.

PMID- 16787708
TI  - Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in
      patients with Parkinson's disease.
AB  - Elevated levels of homocysteine have been observed in Parkinson's disease (PD)
      patients treated with levodopa. However, it is not studied if duration of PD or
      PD per se is associated with hyperhomocysteinemia. In the present study, the
      levels of homocysteine in 99 levodopa-treated PD patients, 15 untreated PD
      patients and 100 controls were examined. We focused on the influence of levodopa
      dose, duration of therapy and disease as well as genetic (C677T
      methylenetetrahydrofolate reductase (MTHFR) polymorphism) and environmental
      factors. We found that levodopa-treated PD patients had elevated homocysteine
      plasma levels as compared to controls (p < 0.05), but the levels did not depend
      on levodopa doses. Another factor influencing homocysteine level was the duration
      of PD (p < 0.001). The frequency of allele C677T of MTHFR gene did not differ
      between PD and controls. In conclusion, hyperhomocysteinemia is associated with
      the duration of PD and levodopa treatment and possibly also with PD per se.

PMID- 16787710
TI  - Bovine hypodermosis: prevalence and economic significance in southern Punjab,
      Pakistan.
AB  - Prevalence and economic losses of warble fly infestation (WFI) in cattle and
      buffaloes were recorded in Dera Ghazi Khan and Rajan Pur districts of southern
      Punjab (Pakistan). A total of 18,000 cattle and 9000 buffaloes were examined in
      the field and slaughter house. Only one species of Hypoderma, i.e. Hypoderma
      lineatum was recorded from this area. The prevalence of WFI was higher in
      slaughter house versus field, cattle versus buffaloes, males versus females, and
      young versus old animals in both the districts. The highest month-wise prevalence
      was recorded in December and the lowest in July. Organ-wise prevalence of WFI was
      highest in oesophagus followed in order by rumen and spleen. The economic losses
      based on the value of warbled and warble-free hides were estimated as Rs. 22.8
      million per annum (currency exchange rate is Rs. 57.5=US 1 dollar).

PMID- 16787711
TI  - Efficiency of Duddingtonia flagrans against Trichostrongyle infections of sheep
      on mountain pastures.
AB  - The control of sheep nematode parasites in extensive mountain/transhumant
      management systems using the nematophagous fungus Duddingtonia flagrans was
      assessed in this study. Two groups of Churra Tensina ewes were allowed to graze
      for 8 weeks in autumn on two separate paddocks of infected pasture near their
      winter sheds in the valley. At lambing, ewes and their twin lambs were turned out
      into the same paddocks for the following 12 weeks. One group of ewes received a
      daily dose of 5 x 10(5) chlamydospores of Duddingtonia flagrans/kg live weight
      per day both in autumn and in spring, while the other group was used as a non
      treated control. Daily dosing of grazing ewes with the fungus D. flagrans had a
      clear effect on reducing autumn pasture contamination. This had a subsequent
      effect on the over-wintering larvae population that was confirmed by a 20% lower
      worm burden of tracer lambs kept in early spring on the paddock previously grazed
      by fungus treated ewes. In spring, pasture contamination was also significantly
      reduced in the paddock grazed by fungi-treated ewes and their lambs showed a 61%
      lower worm burden and a better performance than the control lambs. Results herein
      show that fungal spores fed to sheep at critical times with regard to the
      epidemiology of parasite infection, can have a significant effect on the
      infective larvae present on pasture, which could further improve lambs
      performance. This novel approach to parasite control would be of interest amongst
      both organic and conventional sheep farmers operating in mountain regions.

PMID- 16787712
TI  - Ethanol vapor self-administration in adult C57BL/6J male mice.
AB  - To determine if ethanol vapor is reinforcing, chambers with two nose-poke devices
      were used. First, C57BL/6J mice were trained to nose-poke at one (FR port) and
      then to hold a nose-poke for at least 1 s at the second (reward port) for 10%
      sucrose reinforcement. When mice held reward port nose-pokes for > or = 1 s on
      95% of session trials, ethanol vapor (0.05%, w/v) or clean air replaced sucrose.
      In experiment 1, the FR requirement at the FR port was incremented from 1 to 8.
      Ethanol vapor (n=3) or clean air (n=3) was delivered for 1 s following a single
      nose-poke at the reward port after completing response requirements at the FR
      port. Nose-pokes at the FR port increased with increasing FR to maintain ethanol
      vapor intake, while clean air intake and its associated responding extinguished.
      In experiment 2, mice (n=4) controlled the duration of ethanol vapor delivery by
      providing vapor for as long as the mouse held a single poke in the reward port
      after completing response requirements at the FR port. Nose-pokes at the FR port
      increased with increasing FR to maintain ethanol vapor intake at the reward port.
      These findings indicate that ethanol vapor is reinforcing in adult C57BL/6J male
      mice.

PMID- 16787713
TI  - Substance abuse prevention intervention research with Hispanic populations.
AB  - Selected studies with specific relevance to substance abuse prevention
      interventions with Hispanic youth and families were examined to identify prior
      findings and emerging issues that may guide the design of future substance abuse
      prevention intervention research and its implementation with Hispanic
      populations. The origins of prevention research and role of risk and protective
      factors are examined, including culturally-specific risk and protective factors
      for Hispanic populations. Correlational studies, non-experimental interventions,
      and randomized controlled trials were examined for the period of 1974-2003. The
      literature search yielded 15 articles selected for this review that exhibited
      adequate methodological rigor. An added search for more recent studies identified
      three additional articles, for a total of 18 prevention intervention articles
      that were reviewed. Theoretical and methodological issues and recommendations are
      presented for future research aimed at improving the efficacy and effectiveness
      of future prevention intervention studies and their cultural relevance for
      Hispanic populations.

PMID- 16787714
TI  - Tissue-specific sensitivity to AID expression in transgenic mouse models.
AB  - Activation-induced cytidine deaminase (AID), an enzyme with homology to members
      of the APOBEC family, is involved in somatic hypermutation (SHM) of
      immunoglobulin (Ig) genes, either by direct deamination of DNA or by an indirect
      action through its putative RNA editing activity. AID is able to mutate both Ig
      like reporter constructs and selected non-Ig genes in normal B cells and in other
      cells when ectopically overexpressed in mammalian cells and transgenic mice.
      However, in spite of the fact that in these transgenic animals AID activity was
      driven by an ubiquitous promoter, only T lymphomas and lung adenomas occurred. In
      the present work, we constructed three sets of transgenic mice in which AID was
      under the control of lck, HTLV-I and MMTV promoters, respectively. The lck/AID
      mice developed thymic lymphomas with variable but high efficiency, while no tumor
      was detected in HTLV-I/AID mice after two years of monitoring. Four MMTV/AID
      founder mice died with an atypical clinical picture, although no mammary tumor
      was found. These findings suggest that additional factors, present in thymocytes
      but not in other tissues or in lymphoid cells at different stages of
      differentiation, are needed for AID to fully manifest its tumorigenic potential
      in mouse. Alternatively, the display of full AID mutagenic and transforming
      activity could be related to the existence of physiologic DSBs which occur in
      both thymocytes and switching B cells.

PMID- 16787715
TI  - Adherent and invasive Escherichia coli are associated with persistent bovine
      mastitis.
AB  - Bovine mastitis caused by Escherichia coli has traditionally been viewed as a
      transient infection. However, E. coli can also cause clonal persistent
      intramammary infection (IMI) in dairy cows. In this study, we explored the
      possibility that E. coli strains associated with persistent IMI are better able
      to adhere to, invade, survive and replicate in cultured mammary epithelial cells
      (MAC-T) than transient strains, and examined their serotype, overall genotype,
      phylogenetic group, and the presence of known virulence genes. Both transient and
      persistent E. coli strains adhered to MAC-T cells, but persistent strains invaded
      MAC-T cells 2.6-63.5 times more than transient strains. Blocking the
      adhesin/invasin FimH with mannose diminished but did not eliminate adhesion and
      invasion of any strain. Cytoskeletal and protein kinase inhibitors cytochalasin
      D, colchicine, genistein and wortmannin dramatically reduced invasion of MAC-T
      cells by both strains. All of the persistent strains, but only one transient
      strain, were able to survive and replicate intracellularly in MAC-T cells over 48
      h. Transient and persistent strains displayed heterogeneous serotypes and overall
      genotypes, but similar phylogeny (group A), and lacked virulence genes of
      invasive E. coli. We have found that E. coli strains associated with persistent
      IMI are better able to invade and replicate within cultured mammary epithelial
      cells than transient strains. The invasion process involves the host cytoskeleton
      and signaling cascades and is not FimH dependent. Our findings suggest that the
      invasion of mammary epithelial cells and intracellular survival play an important
      role in the pathogenesis of persistent E. coli mastitis.

PMID- 16787716
TI  - Effect of cryopreservation on viability, activation and growth of in situ and
      isolated ovine early-stage follicles.
AB  - Isolated or cortical tissue-enclosed (in situ) sheep early-stage follicles were
      exposed to 1.5 M dimethyl sulfoxide (DMSO), ethylene glycol (EG) or unexposed, or
      frozen/thawed in the presence of these cryoprotectants and then cultured for 5
      days in enriched minimal essential medium (MEM) or not cultured. Cultured and
      uncultured follicles were classified as non-viable/viable when they were
      stained/not stained with trypan blue, respectively. Follicular diameter was
      measured and the percentages of primordial and developing follicles calculated.
      Exposure of isolated or in situ follicles to DMSO or EG led to a marked decrease
      in the percentage of viable follicles. The percentage of viable isolated and in
      situ follicles further decreased when they were in vitro-cultured for 5 days, EG
      exposed follicles generally showing a more damaging effect than DMSO-exposed
      follicles. Cultured follicles, both isolated and in situ, which were exposed to
      EG and DMSO, as well as in situ follicles, which had been frozen/thawed in the
      presence of one of these cryoprotectants, showed similar growth rates as
      cultured, untreated follicles, while in these groups significantly lower
      percentages of primordial follicles and higher percentages of more advanced
      follicular stages were observed. Among the treated groups, the highest percentage
      (71-75%) of developing follicles was observed after culturing cryoprotectant
      exposed isolated follicles. In contrast, when cryopreserved, isolated follicles
      were cultured, they did not increase in diameter and did not develop into more
      advanced stages. In conclusion, exposure to or cryopreservation in the presence
      of EG and DMSO, as well as their further in vitro culture, negatively affected
      the viability of ovine isolated and in situ early-stage follicles. In vitro
      growth of early-stage follicles and activation of primordial follicles were
      better maintained when follicles had been frozen/thawed and cultured in situ.

PMID- 16787717
TI  - Dose dependent effect of GnRH analogue on pregnancy rate of repeat breeder
      crossbred cows.
AB  - The aim of this study was to investigate the effect of treating repeat breeder
      dairy crossbred cows with different doses of GnRH analogue through i.m. at the
      time of artificial insemination, on pregnancy rates from their first service
      after treatment and overall pregnancy rates. One hundred and thirty seven
      crossbred dairy cows with a history of repeat breeding and eligible after 6-8
      infertile services but clinically free of diseases were selected for the study.
      The animals were randomly divided into three groups. Group 1 (n = 55) cows were
      treated intramuscularly with each 20 microg Buserelin-acetate (Receptal, Hoechst
      Roussel Vet GmbH) at the time of artificial insemination. Group 2 (n = 40) cows
      were treated intramuscularly with each 10 microg Buserelin-acetate at the time of
      artificial insemination. Group 3 (n = 42) cows were treated intramuscularly with
      saline as control at the time of artificial insemination. The first service
      pregnancy rates in Groups 1-3 were 45, 25 and 17%, respectively. Similarly, the
      overall conception rates in Groups 1-3 were 87, 58 and 48%, respectively. The
      results indicated that the pregnancy rate in crossbred cows could be improved by
      the GnRH treatment. The higher dose of GnRH significantly increased (P < 0.05)
      the first service as well as overall pregnancy rate in a dose dependent manner in
      repeat breeder crossbred cow bred previously 6-8 times unsuccessfully.

PMID- 16787718
TI  - Localization of Period 1 mRNA in the ruminant oocyte and investigations of its
      role in ovarian function.
AB  - The clock gene Period 1 (Per1) may be a prolificacy gene, because it localized to
      the mouse oocyte and Per1-null drosophila shed fewer eggs. Because Per1 mapped to
      a region of mouse chromosome 11 syntenic to bovine chromosome 19 where a
      quantitative trait loci (QTL) for ovulation rate existed, we hypothesized that
      Per1 influenced folliculogenesis and ovulation rate in ruminants. Ovarian cortex
      was collected at slaughter on days 5, 12, 15, 17, and 20 after estrus for real
      time RT-PCR evaluation of Per1 mRNA expression in Dorset (n = 18), Romanov (n =
      10), Romanov/Dorset (n = 21), and Composite (n = 22) ewes. Ovarian cortex was
      also collected from cows selected for increased ovulation rate (n=37) or
      unselected controls (n = 28) on days 4, 5, and 6 of the estrous cycle for in situ
      hybridization and real-time RT-PCR. To examine the role of Per1 in early
      follicular development, ovarian cortex from neonatal calves (n = 5) was cultured
      for 10 days and Per1 mRNA levels were measured on day 0 and on day 10 of culture.
      The primers generated a 483bp amplicon with 100% sequence homology to bovine
      RIGUI-like protein (Per1). In silico mapping of this sequence placed Per1 on
      bovine chromosome 19; however, it was 20cM from the QTL. Per1 mRNA expression was
      unaffected by prolificacy, day of the cycle, or pregnancy status in ewes or cows.
      The riboprobe hybridized to oocytes of bovine preantral and antral follicles. In
      bovine ovarian cortical cultures on day 0, the tissue contained mostly primordial
      follicles (5.6+/-0.6 follicles/section); however, after 10 days in culture, the
      number of primordial follicles per section decreased (0.5 follicles/section) and
      the number of primary follicles increased as follicles activated (day 0 = 0.5+/-
      0.6 versus day 10 = 10.4 +/-0.6 primary follicles/section; P < 0.001). Per1 mRNA
      did not change over time in culture. We conclude that Per1 mRNA is expressed by
      ruminant oocytes in preantral and antral follicles; however, its physiological
      role in mammalian ovarian function remains to be elucidated.

PMID- 16787719
TI  - Raloxifene therapy interacts with serum osteoprotegerin in postmenopausal women.
AB  - OBJECTIVES: Osteoprotegerin (OPG) is a protein expressed by osteoblasts that,
      linking the receptor activator of nuclear factor kappaB (RANK) ligand (RANKL),
      produced by osteoblasts, blocks the process of osteoclastic differentiation and
      modulates osteoclastic apoptosis. Raloxifene (RAL) stimulates the production of
      OPG from osteoblasts, as demonstrated in vitro, carring out their antiresorption
      activity, at least in part, as means of the OPG/RANK/RANKL system. The aim of
      this study was to evaluate in vivo if the RAL treatment of postmenopausal women
      was associated to changes in serum OPG; moreover, to evaluate the serum changes
      of bone turnover modulators interleukin-6 (IL-6) and C-telopeptides of type-1
      collagen (CrossLaps). METHODS: A prospective, randomized, placebo-controlled
      study was designed. A group of consecutive healthy postmenopausal women (n=40)
      referred to II Menopause Centre of the Department of Gynaecology of Second
      University of Naples for climacteric syndrome was enrolled and divided in two
      groups: (n=20) postmenopausal women received for 6 months oral raloxifene (60
      mg/day) versus (n=20) postmenopausal women received placebo tablets. RESULTS:
      Serum OPG levels in postmenopausal women after RAL treatment are statistically
      significant increased (P<0.001) versus baseline (P=0.007) versus placebo.
      CONCLUSIONS: These in vivo data demonstrate that RAL could improve osteoporosis,
      also through an increase of OPG production by osteoblasts.

PMID- 16787720
TI  - Skin penetration enhancement of mefenamic acid by ethanol and 1,8-cineole can be
      explained by the 'pull' effect.
AB  - The simultaneous skin permeation of drug and penetration enhancer have been
      studied in vitro. Simple formulations of mefenamic acid in PEG400 incorporating
      various proportions of ethanol or 1,8-cineole were prepared and applied to
      porcine ear skin in diffusion cells under infinite conditions. Receptor phases
      were assayed for mefenamic acid by HPLC and ethanol or 1,8-cineole by GC.
      Concentration-dependent permeation profiles were obtained for both ethanol or 1,8
      cineole, in addition to concentration-dependent enhancement of mefenamic acid.
      When the steady state flux of mefenamic acid was plotted against ethanol or 1,8
      cineole, linear relationships were observed with r2 values of 0.988 and 0.999,
      respectively. The close connection between rates of excipient and solute
      permeation is generally referred to as the 'pull' (or 'drag') effect, where in
      this case permeation of the enhancer facilitated permeation of the solute. This
      appears to be sufficient to account for the enhancing activity of ethanol and 1,8
      cineole, notwithstanding initial modulations that may occur within the stratum
      corneum.

PMID- 16787721
TI  - Long-term studies on the stability and oral bioavailability of cyclosporine A
      nanoparticle colloid.
AB  - The present study was geared at the long-term stability and the changes in oral
      bioavailability of CyA Eudragit S100 nanoparticles stabilized by suspending
      agents. CyA Eudragit S100 nanoparticle colloids were prepared by quasi-emulsion
      solvent diffusion technique and they were mixed with Xanthan gum to obtain
      suspended nanoparticle colloids. The suspended nanoparticle colloids were
      preserved at different temperatures for different period of time, as long as 18
      months. During the storage period, the CyA concentration, particle size, pH and
      viscosity were determined. The results indicated that CyA concentration, particle
      size and viscosity of the colloids had no obvious change. However, the pH
      increased slightly from 5.5 to about 6.4. The results of bioavailability and
      pharmacokinetic study revealed that all formulations of nanoparticles showed
      higher C(max) and higher AUC(0-24) values than that of reference (Neoral). The
      relative bioavailability of S-CyA-S100 NP initial compared with Neoral was
      162.8%. The C(max) and AUC(0-24) values of nanoparticle formulations at 12 and 18
      months were both lower than that of the initial. The bioequivalency was suggested
      between the tested nanoparticle formulations at the initial and 12 months. It was
      deduced by surface analysis, TEM observation, in vitro release as well as the
      characteristics of Eudragit S100 that the decrease in bioavailability might be
      due to the pH change of the nanoparticle colloid.

PMID- 16787722
TI  - Formation of hollow core granules by fluid bed in situ melt granulation:
      modelling and experiments.
AB  - Granules with a characteristic core-shell internal structure have been formed by
      in situ melt fluid-bed granulation, using d-mannitol primary solid particles and
      poly-ethylene glycol (PEG-6000) binder. The effect of binder particle size and
      binder/solids ratio on granule size distribution was systematically investigated.
      The mean granule size was found to be directly proportional to the binder
      particle size. The binder amount did not measurably affect the granule size, only
      the fraction of un-granulated fines. The microstructure of the granules was
      analysed by X-ray micro-tomography; the average shell thickness in the granules
      was found to depend on the binder/solids ratio, and the core volume was found to
      be directly proportional to the binder particle size. However, for binder
      particle size below a certain value the core-shell structure disappeared. A
      mathematical model based on a layering growth mechanism has been proposed and
      found to be consistent with experimental data. The proposed growth mechanism was
      confirmed by creating granules with bi-modal size distribution using a mixture of
      differently sized binder seeds.

PMID- 16787723
TI  - Anti-inflammatory effects of an ethanolic extract from Clematis mandshurica Rupr.
AB  - Clematis mandshurica Rupr (Ranunculaceae) roots are used in traditional Korean
      medicine to treat inflammation-related diseases. Therefore, we undertook to
      investigate their inhibitory effect on inflammation under non-cytotoxic
      conditions. The ethanolic extract of Clematis mandshurica at 100 microg/ml was
      found to significantly block the production of the pro-inflammatory mediators,
      nitric oxide (NO) and prostaglandin E(2) (PGE(2)), in lipopolysaccharide
      (LPS)/interferon(IFN)-gamma-stimulated mouse peritoneal macrophages, by up to 77%
      and 59%, respectively. In addition, it significantly inhibited cell proliferation
      and cytokine production (interleukin (IL)-2 and IFN-gamma) in splenocytes
      stimulated with Con A (concanavalin A; 5 microg/ml). Furthermore, when
      splenocytes from extract fed mice (200 mg/kg for 2 weeks) were activated with Con
      A, cell proliferation and the production of IL-2 and IFN-gamma were significantly
      inhibited. In addition, the extract reduced in vivo inflammation in oxazolone
      induced delayed type hypersensitivity (DTH) model mice. Taken together, these
      data suggest that Clematis mandshurica is able to ameliorate inflammatory disease
      by exerting an anti-inflammatory effect in cases of proinflammatory and cell
      mediated inflammation.

PMID- 16787725
TI  - Postmortem diagnosis of sepsis.
AB  - Human sepsis is a spectrum of pathophysiological changes in the host system
      resulting from a generalized activation and systemic expression of the host's
      inflammatory pathways in response to infection. Since autopsy findings and
      routine histology in cases of suspected fatal sepsis are most often unspecific
      and unconvincing, a number of studies has recently dealt with different methods
      and markers to better define criteria for the postmortem diagnosis of sepsis.
      Research carried out on specimens obtained postmortem from sepsis-associated
      fatalities is an important tool to improve our understanding of inflammatory
      organ changes and the associated underlying pathophysiological mechanisms. One
      pitfall the investigator has to be aware of is how to select appropriate case
      material that constitutes the basis for the setting-up of reference values that
      derive from such studies. Since no scientific studies have investigated the value
      of cardiac blood samples in the present context, autopsy blood samples for the
      determination of biochemical sepsis markers have to derive from the femoral vein.
      In both sepsis cases as well as controls, the time of death has to be well
      defined.

PMID- 16787724
TI  - Study of hypoglycaemic and hypolipidemic effects of Inula viscosa L. aqueous
      extract in normal and diabetic rats.
AB  - The present study was designed to examine the hypoglycaemic and hypolipidemic
      activity of Inula viscsa aqueous extract on normal and diabetic rats. In normal
      rats, a significant reduction in blood glucose levels 2 h was observed after a
      single oral administration (p<0.001). Repeated daily oral administration
      significantly reduced blood glucose levels after 4 days of treatment (p<0.01). In
      diabetic rats, a significant reduction in blood glucose levels was observed 1 h
      after a single oral administration (p<0.001). Repeated oral administration
      reduced blood glucose levels at the 4th day (p<0.001). No change in total plasma
      cholesterol and triglyceride levels was observed after both a single and repeated
      oral administration in both normal and diabetic rats. In addition, plasma insulin
      levels and body weight remained unchanged after 15 days of repeated oral
      administration in normal and diabetic rats. We conclude that Inula viscosa
      possess a hypoglycaemic but not hypolipidemic activity in normal and diabetic
      rats. The observed hypoglycaemic activity seems to be independent of insulin
      secretion.

PMID- 16787726
TI  - Suicide due to oral ingestion of lidocaine: a case report and review of the
      literature.
AB  - The Authors describe a rare case of suicide in a 31-year-old woman, due to oral
      ingestion of lidocaine; the histological and toxicological findings are discussed
      to provide useful information to the present experience with this particular
      modality of death. Histological examination revealed generalized stasis. In the
      myocardium we observed segmentation of the myocardial cells and/or widening of
      intercalated discs and associated group of hypercontracted myocardial cells with
      "square" nuclei in line with hyperdistended ones. Non-eosinophilic bands of
      hypercontracted sarcomeres alternating with stretched, often apparently separated
      sarcomeres, small foci of paradiscal contraction band necrosis, and perivascular
      fibrosis were observed too. Lidocaine was detected in the subject's urine through
      immunoenzymatic screening. Toxicological analysis by solid-liquid extraction and
      gas chromatography-mass spectrometry (GC-MS) analysis, was carried out to
      identify and quantify the individual substances present in the biological fluids
      and organs. Lidocaine concentrations were as follows: blood 31 microg/mL, gastric
      content 2.5 g, liver 10 microg/g, kidney 12 microg/g, brain 9 microg/g, spleen 24
      microg/g, lung 84 microg/g, heart 9 microg/g, urine 9 microg/mL, and bile 6
      microg/mL. No other drugs or alcohol were detected. When blood lidocaine reaches
      toxic levels, serious toxic symptoms associated with the central nervous system
      and cardiac system are noted. The overdose of lidocaine produces death from
      ventricular fibrillation or cardiac arrest. In this case, according to
      macroscopic and microscopic findings, the cause of death was most likely cardiac
      and possibly related to ventricular fibrillation.

PMID- 16787728
TI  - Gastric traumatic injuries: CT findings.
AB  - OBJECTIVE: Gastric blunt traumatic injuries are uncommon and their radiological
      appearance has been infrequently reported in medical literature. These injuries
      are difficult to diagnose preoperatively, though they require immediate
      recognition to minimize their otherwise high mortality and morbidity. The aim of
      our study is to describe the radiological appearance of blunt gastric traumatic
      injuries. MATERIALS AND METHODS: Retrospective evaluation of a 25 patients series
      observed between January 1997 and May 2005. RESULTS: We observed rupture of the
      stomach in 20% of cases, in 44% of cases a partial lesion of the stomach, in one
      case a necrotic post-traumatic volvulus, five patients (20%) had benign portal
      pneumatosis, in three patients the stomach was secondarily involved because of a
      diaphragmatic hernia. The fundus resulted to be the most frequently damaged part
      of the stomach (80%). CONCLUSIONS: Blunt traumatic injuries need a careful and
      systematic approach given their economical and social relevance. For these
      reasons uncommon lesions require attention and may be important to search for
      specific findings of gastric lesions.

PMID- 16787729
TI  - Imaging of blunt cerebrovascular injuries.
AB  - Arterial dissection, pseudoaneurysm, arteriovenous fistula, arterial laceration
      and occlusion are uncommon complications of blunt trauma. Angiography has been
      considered the primary method of evaluation to assess for vascular injuries but,
      due to the low frequency of these lesions, its screening role has been
      challenged. Non-invasive imaging, particularly CT angiography (CTA), offers
      definitive advantages and has emerged as a promising diagnostic screening method.
      Angiography is shifting to a rather therapeutic role and the endovascular
      management of these lesions is briefly discussed.

PMID- 16787730
TI  - The role of the radiologist in the management of politrauma patients.
AB  - The management of trauma patients has become a very relevant issue and one of the
      major challenges in the western countries. In the assessment of politrauma
      patients, since the last 2 decades, radiological imaging methods have been
      increasingly used in order to provide a quick and thorough survey of
      craniocerebral, cervical, abdominal, pelvic and limb traumatic injuries. Among
      imaging methods, conventional radiographs (CR) have precise but limited
      indications. In most European hospitals, UltraSonography (US) represents the
      method of choice for patients referred following blunt abdominal trauma, whereas
      multislice computed tomography (MSCT) remains a second-line method of
      investigation, although it provides a fully comprehensive assessment of their
      injuries and allows for their categorization according to the severity of
      traumatic injuries. In fact, injury prevalence, radiation dose exposure, and
      costs represent important considerations in all of the emergency departments,
      where a growing number of patients seeking medical attention is seen. The
      radiologist's task is to decide which imaging method is mostly appropriate after
      initial patient presentation. In the severe politrauma patient, the diagnostic
      endpoint is to identify the nature and extent of the various injuries in order to
      execute a more tailored therapeutic approach: this is the patient in whom a total
      body MSCT has to be performed in order to provide rapid and accurate information
      for a correct management. In the large majority of our patients, who do not show
      the need for a formal hospital admission, after the physical examination has
      revealed the clinical suspicion of minimal single-organ injury, US provides an
      adequate assessment of abdominal traumatic injuries and triage those few who are
      subsequently to be evaluated by means of MSCT. In the majority of this patients
      category, with low to very-low grade of potential injuries, CR can detect all
      types of skeletal fractures (except for the skull and the hips). Overall, the
      role of the emergency radiologist has become of primary importance in the
      management of trauma patients, and this all the more so since development of
      interventional radiology affords therapeutic procedures alternative to surgery.

PMID- 16787731
TI  - The thyroid cancer epidemic: is it the dark side of the CT revolution?
AB  - The rapid increase in CT use since 1990 and especially in the past 10 years has
      been accompanied by a coterminous worldwide increase in incidence of thyroid
      cancer especially in women. Are the two trends independent or related? Specific
      information from many countries and seven American states suggest that the
      relationship is real as no other cause can account fully for the temporal change
      in the frequency of this malignancy. Moreover, newer techniques of CT performance
      with or without the administration of iodinated contrast material favor the
      likelihood of a contingent association of image test utilization and thyroid
      cancer induction.

PMID- 16787732
TI  - Photosensitized degradation of losartan potassium in an extemporaneous suspension
      formulation.
AB  - During development of an extemporaneous suspension formulation for losartan
      potassium, previously unknown degradation products were observed in experimental
      suspensions prepared in a commercial cherry syrup vehicle. These degradates
      increased rapidly when analytical solutions prepared from that suspension were
      exposed to ambient light. The structures of the degradates were determined using
      a combination of preparative HPLC, LC/MS, (13)C and (1)H NMR (1D and 2D), and
      mechanistic chemistry. Each degradate results from destruction of the imidazole
      ring of losartan. Formation of the two major degradates required exposure to
      light (UV or visible) and the presence of oxygen. Experiments using Rose Bengal
      (a singlet oxygen photosensitizer) and 1,4-diazabicyclooctane (DABCO; a singlet
      oxygen quencher) established that the major photodegradates are formed via the
      intermediacy of singlet oxygen. The identity of the photosensitizer in the
      formulation was not unequivocally determined; however, the experiments implicated
      the artificial flavoring in fulfilling this role.

PMID- 16787733
TI  - Identification and analysis of absorbed and metabolic components in rat plasma
      after oral administration of 'Shuangdan' granule by HPLC-DAD-ESI-MS/MS.
AB  - A valid method using liquid chromatography-diode array detection-electrospray
      ionization (ESI) ion trap mass spectrometry was established for the study of the
      absorbed and metabolic components of a Chinese medicine 'Shuangdan' granule in
      rat plasma after oral administration. The plasma samples were acidified with 1M
      hydrochloric acid and extracted with ethyl acetate (EtOAc) of two-fold volume for
      three times. The chromatographic separation was carried out on a Zorbax SB-C18
      column with a linear gradient whereas 0.1% acetic acid/water/acetonitrile was
      used as mobile phase. Mass spectra were acquired in both negative and positive
      modes. More than 20 components including 16 components from 'Shuangdan' granule
      and 5 metabolites were simultaneously identified by comparing their mass spectra
      and retention behavior with reference compounds or literature data. The results
      proved that the established method could be used to identify the structure of
      active components responsible for the pharmacological effects of 'Shuangdan'
      granule.

PMID- 16787734
TI  - Cloning of partial cDNAs for the chicken glucocorticoid and mineralocorticoid
      receptors and characterization of mRNA levels in the anterior pituitary gland
      during chick embryonic development.
AB  - Virtually nothing is known about glucocorticoid receptor (GR) or
      mineralocorticoid receptor (MR) gene expression in any avian species. Here we
      report the cloning of partial cDNAs for chicken GR and MR. These partial cDNAs
      were used as probes to characterize expression of GR and MR mRNA and to identify
      the full-length transcripts within the chicken genome. Chicken GR and MR
      sequences predicted from the genome sequence were compared with those of
      representatives of other vertebrate classes. GR and MR genes are located on
      chicken chromosomes 13 and 4, respectively. Northern blotting and reverse
      transcription-polymerase chain reaction (RT-PCR) results indicate that GR and MR
      are widely expressed in many tissues. Characterization of mRNA levels in the
      anterior pituitary gland during chick embryonic development by quantitative real
      time RT-PCR demonstrates decreased MR and increased GR gene expression between
      embryonic days 12 and 17. Plasma levels of corticosteroids increased during this
      same period. This is the first study of GR and MR gene expression in any avian
      species and the first analysis of changes in pituitary MR gene expression during
      embryonic development of any species.

PMID- 16787735
TI  - Effect of suppression of plasma prolactin on luteinizing hormone concentration,
      intersequence pause days and egg production in domestic hen.
AB  - The aim of this study was to investigate the effects of suppression of plasma
      prolactin (PRL) concentration on circulating concentrations of luteinizing
      hormone (LH), progesterone (P(4)), estradiol (E(2)beta), pause days and egg
      production in birds later in the reproductive period. Twenty-four White Leghorn
      birds of same age group were divided into two groups of 12 in each. Birds of each
      group were administered s/c either with placebo (control group) or equal volumes
      of anti PRL agent (2-bromo-alpha-ergocriptine) solution containing at 100
      microg/kg body weight/hen/week (treated group) from 72 to 82 weeks of age. Egg
      production and inter sequence pauses were recorded daily from both the groups.
      Plasma PRL, LH, E(2)beta and P(4) concentrations were estimated in blood samples
      collected at weekly intervals. At 77th weeks of age, blood samples from treated
      and control birds were obtained every 3h for 36h to study the surges of LH. It
      was found that plasma PRL concentration was lower (p<0.01) in bromocriptine
      treated birds with high concentrations of LH, its 3h LH surges, E(2)beta and P(4)
      in plasma. Higher egg production, less pause days in treated birds may be the
      result of low PRL concentration, associated with positively correlated responses
      of high concentrations of LH (with regular interval and duration of LH surges),
      E(2)beta and P(4) concentration required for completion of egg formation and
      oviposition. In conclusion, bromocriptine administration decreased (p<0.01) PRL
      concentration increased (p<0.01) steroid hormones and LH surges, for egg
      formation and oviposition and enabled the birds to lay more eggs even later in
      the productive period with the available resources under normal husbandry
      practices.

PMID- 16787736
TI  - Oocytes cryopreservation: state of art.
AB  - In the present review article we sought to analyze, on the basis of a systematic
      review, the indications, rationale of oocytes cryopreservation, as well as the
      techniques that improved the aforementioned procedure in order to higher the
      pregnancy rate in women undergoing that procedure. Moreover, we pointed out the
      importance of oocytes cryopreservation in the research field as oocyte banking
      may be of utmost importance to increase the availability of oocytes for research
      applications such as genetic engineering or embryo cloning. Oocyte freezing has
      25 year of history alternating successes and setbacks. Human oocytes have a
      delicate architecture but are freezable. Clinical efficiency remains low, but
      healthy children have been born, indicating that chromosomally normal embryos can
      originate from frozen oocytes. Freezing protocols are not yet optimal and it is
      now desirable to combine empirical and theoretical knowledge.

PMID- 16787737
TI  - Local multidimensional scaling.
AB  - In a visualization task, every nonlinear projection method needs to make a
      compromise between trustworthiness and continuity. In a trustworthy projection
      the visualized proximities hold in the original data as well, whereas a
      continuous projection visualizes all proximities of the original data. We show
      experimentally that one of the multidimensional scaling methods, curvilinear
      components analysis, is good at maximizing trustworthiness. We then extend it to
      focus on local proximities both in the input and output space, and to explicitly
      make a user-tunable parameterized compromise between trustworthiness and
      continuity. The new method compares favorably to alternative nonlinear projection
      methods.

PMID- 16787738
TI  - Spherical self-organizing map using efficient indexed geodesic data structure.
AB  - The two-dimensional (2D) Self-Organizing Map (SOM) has a well-known "border
      effect". Several spherical SOMs which use lattices of the tessellated icosahedron
      have been proposed to solve this problem. However, existing data structures for
      such SOMs are either not space efficient or are time consuming when searching the
      neighborhood. We introduce a 2D rectangular grid data structure to store the
      icosahedron-based geodesic dome. Vertices relationships are maintained by their
      positions in the data structure rather than by immediate neighbor pointers or an
      adjacency list. Increasing the number of neurons can be done efficiently because
      the overhead caused by pointer updates is reduced. Experiments show that the
      spherical SOM using our data structure, called a GeoSOM, runs with comparable
      speed to the conventional 2D SOM. The GeoSOM also reduces data distortion due to
      removal of the boundaries. Furthermore, we developed an interface to project the
      GeoSOM onto the 2D plane using a cartographic approach, which gives users a
      global view of the spherical data map. Users can change the center of the 2D data
      map interactively. In the end, we compare the GeoSOM to the other spherical SOMs
      by space complexity and time complexity.

PMID- 16787739
TI  - Atypical protein kinase C in glucose metabolism.
AB  - Type 2 diabetes mellitus is a multigenic disease with evident genetic
      predisposition, and complex pathogenesis in which environmental and genetic
      factors interact. The disorder of body utilization glucose is a crucial reason
      for causing diabetes. Atypical PKCs, belonging to Ser/Thr protein kinase, have
      many important biological functions in vivo, and may be involved in the
      pathogenesis of diabetes mellitus. APKCs participate in glucose metabolism by
      regulating glucose transport and absorption, glycogen synthesis, and insulin
      secretion. The exact mechanism by which aPKCs participate in glucose metabolism
      remains unclear. So far, the clarification of which will be helpful for the
      prevention and cure of type 2 diabetes.

PMID- 16787740
TI  - Lack of benefit of linoleic and alpha-linolenic polyunsaturated fatty acids on
      seizure latency, duration, severity or incidence in rats.
AB  - BACKGROUND: Polyunsaturated fatty acids have been reported to increase seizure
      threshold and to reduce seizure duration and severity in rats. OBJECTIVE: The
      purpose of the present study was to test the anticonvulsant effects of an
      essential fatty acid mixture containing linoleic and alpha-linolenic acids at a
      4:1 ratio (SR-3 compound), using the pentylenetetrazol seizure model in Long
      Evans hooded rats. RESULTS: There were no significant effects of SR-3 on seizure
      latency, duration or severity (P>0.05). There were also no significant
      differences in the incidence of myoclonic jerks, forelimb and hindlimb clonus,
      forelimb and hindlimb tonus or running fits in rats that received SR-3, as
      compared to control rats (P>0.05). CONCLUSION: Linoleic and alpha-linolenic
      polyunsaturated fatty acids have no beneficial effects on seizure latency,
      duration, average severity or incidence.

PMID- 16787741
TI  - Metabotropic glutamate receptors as a strategic target for the treatment of
      epilepsy.
AB  - Epilepsy is a chronic neurological disorder that has many known types, including
      generalized epilepsies that involve cortical and subcortical structures. A
      proportion of patients have seizures that are resistant to traditional anti
      epilepsy drugs, which mainly target ion channels or postsynaptic receptors. This
      resistance to conventional therapies makes it important to identify novel targets
      for the treatment of epilepsy. Given the involvement of the neurotransmitter
      glutamate in the etiology of epilepsy, targets that control glutamatergic
      neurotransmission are of special interest. The metabotropic glutamate receptors
      (mGluRs) are of a family of eight G-protein-coupled receptors that serve unique
      regulatory functions at synapses that use the neurotransmitter glutamate. Their
      distribution within the central nervous system provides a platform for both
      presynaptic control of glutamate release, as well as postsynaptic control of
      neuronal responses to glutamate. In recent years, substantial efforts have been
      made towards developing selective agonists and antagonists which may be useful
      for targeting specific receptor subtypes in an attempt to harness the therapeutic
      potential of these receptors. We examine the possibility of intervening at these
      receptors by considering the specific example of absence seizures, a form of
      generalized, non-convulsive seizure that involves the thalamus. Views of the
      etiology of absence seizures have evolved over time from the "centrencephalic"
      concept of a diffuse subcortical pacemaker toward the "cortical focus" theory in
      which cortical hyperexcitability leads the thalamus into the 3-4 Hz rhythms that
      are characteristic of absence seizures. Since the cortex communicates with the
      thalamus via a massive glutamatergic projection, ionotropic glutamate receptor
      (iGluR) blockade has held promise, but the global nature of iGluR intervention
      has precluded the clinical effectiveness of drugs that block iGluRs. In contrast,
      mGluRs, because they modulate iGluRs at glutamatergic synapses only under certain
      conditions, may quell seizure activity by selectively reducing hyperactive
      glutamatergic synaptic communication within the cortex and thalamus without
      significantly affecting normal response rates. In this article, we review the
      circuitry and events leading to absence seizure generation within the
      corticothalamic network, we present a comprehensive review of the synaptic
      location and function of mGluRs within the thalamus and cerebral cortex, and
      review the current knowledge of mGluR modulation and seizure generation. We
      conclude by reviewing the potential advantages of Group II mGluRs, specifically
      mGluR2, in the treatment of both convulsive and non-convulsive seizures.

PMID- 16787742
TI  - Cell surface acid-base properties of Escherichia coli and Bacillus brevis and
      variation as a function of growth phase, nitrogen source and C:N ratio.
AB  - Potentiometric titration has been conducted to systematically examine the acid
      base properties of the cell surfaces of Escherichia coli K-12 and Bacillus brevis
      as a function of growth phase, nitrogen source (ammonium or nitrate), and carbon
      to nitrogen (C:N) ratio of the growth substrate. The two bacterial species
      revealed four distinct proton binding sites, with pK(a) values in the range of
      3.08-4.05 (pK(1)), 4.62-5.57 (pK(2)), 6.47-7.30 (pK(3)), and 9.68-10.89 (pK(4))
      corresponding to phosphoric/carboxylic, carboxylic, phosphoric, and
      hydroxyl/amine groups, respectively. Two general observations in the data are
      that for B. brevis the first site concentration (N(1)), corresponding to
      phosphoric/carboxylic groups (pK(1)), varied as a function of nitrogen source,
      while for E. coli the fourth site concentration (N(4)), corresponding to
      hydroxyl/amine groups (pK(4)), varied as a function of C:N ratio.
      Correspondingly, it was found that N(1) was the highest of the four site
      concentrations for B. brevis and N(4) was the highest for E. coli. The
      concentrations of the remaining sites showed little variation. Finally,
      comparison between the titration data and a number of cell surface compositional
      studies in the literature indicates one distinct difference between the two
      bacteria is that pK(4) of the Gram-negative E. coli can be attributed to hydroxyl
      groups while that of the Gram-positive B. brevis can be attributed to amine
      groups.

PMID- 16787743
TI  - Preparation and characterization of uniform-sized chitosan microspheres
      containing insulin by membrane emulsification and a two-step solidification
      process.
AB  - Chitosan microsphere has important application in controlled release of protein
      and peptide drug, because it shows excellent mucoadhesive and permeation
      enhancing effect across the biological surfaces. In the conventional preparation
      methods of chitosan microsphere, the W/O emulsion was usually prepared by
      mechanical stirring method, and then the droplets were solidified by
      glutaraldehyde. There existed limitation and shortage such as broad size
      distribution, de-activity of bio-drug and difficulty in drug release because
      protein and peptide drug have the same amino group as chitosan. In this study, we
      established a method to prepare uniform-sized microsphere, and solve above
      problems by combining a special membrane emulsification technique and a step-wise
      crosslinking method. That is, the chitosan/acetic acid aqueous solution was
      pressed through the uniform pores of a porous glass membrane into a
      paraffin/petroleum ether mixture containing PO-500 emulsifier, to form a W/O
      emulsion with uniform droplet size. Then, the uniform droplets were solidified by
      a two-step crosslinking method. At the first step, tripolyphosphate (TPP)
      solution was dropped gradually in the emulsion, TPP diffused into the droplet to
      crosslink chitosan by an ionic linkage, generating a microgel. At the second
      step, an adequate amount of glutaraldehyde was added. The solidification
      conditions of the two-step process were optimized by investigating the effects of
      solidification conditions on morphology of microspheres, encapsulation efficiency
      (EE), drug activity and release profile in vitro. The suitable preparative
      conditions were determined as follows: pH value of aqueous phase and TPP solution
      was 3.5-4.0, the molar ratio of amino group of chitosan to aldehyde group of
      glutaraldehyde was 1:1 and the crosslinking time of glutaraldehyde was 60 min.

PMID- 16787744
TI  - Clinical history in gastroesophageal cough.
AB  - Gastroesophageal disease, a common cause of chronic cough, is often poorly
      recognised. We reviewed the presenting history of 47 chronic cough patients who
      had been proven to have gastroesophageal disease by oesophageal function testing.
      Fourty-seven patients (26 female), were enroled. Symptoms which were most common
      included: cough on phonation, on rising from bed, associated with certain foods
      or with eating in general. Symptoms known to be associated with laryngopharyngeal
      reflux, such as throat clearing, dysphonia, globus and dysphagia were also
      associated. Heartburn or indigestion was present in 63% of those questioned.
      These data show that symptoms associated with reflux in chronic coughers differ
      from those commonly perceived to be characteristic of classical heartburn
      associated reflux. These data suggest that, contrary to previous reports, a
      symptom complex which is characteristic of reflux cough can be identified.

PMID- 16787745
TI  - Biochemical and immunochemical characterization of the antigen-antibody reaction
      on a non-toxic biomimetic interface immobilized red blood cells of crucian carp
      and gold nanoparticles.
AB  - A special protein assay system based on a highly hydrophilic, non-toxic and
      conductive biominetic interface has been demonstrated. To fabricate such assay
      system, red blood cells of crucian carp (RBC) was initially grown on a glassy
      carbon electrode surface (GCE) deposited nano-sized gold particles (GPs), a
      second gold nanoparticle layer (NG) was then absorbed on the RBC surface, and
      finally mammary cancer 15-3 antibody (anti-CA15-3) was attached on the functional
      RBC surface. A competitive immunoassay format was employed to detect CA15-3 with
      horseradish peroxidase (HRP)-labeled CA15-3 as tracer and hydrogen peroxide as
      enzyme substrate. When the immunosensor was incubated into a mixture solution
      containing HRP-labeled CA15-3 and CA15-3 sample for 1h at 37 degrees C, the
      amperometric response decreased with the increment of CA15-3 sample
      concentration. AFM images of the modified layer revealed a uniform distribution
      of protein and nanogold. In situ QCM and electrochemical measurements
      demonstrated that the wanted antibody-antigen reactions should occur with high
      specificity and selectivity. The specific immunoassay system can be developed
      further to yield sophisticated structures for other proteins.

PMID- 16787746
TI  - Altered balance control following concussion is better detected with an attention
      test during gait.
AB  - The purpose of this study was to examine the effects of concussion on gait
      stability when either a cognitive or motor perturbation is imposed. Fourteen
      individuals suffering from a grade II concussion and 14 matched controls
      performed a single task of level walking, a continuous sequential question and
      answer task while walking, and an obstacle-crossing task. Common gait
      spatial/temporal measurements, whole-body center of mass motion, and center of
      pressure trajectory were assessed. Concussed individuals adopted a more
      conservative strategy to maintain gait stability. Some measurements indicating
      conservative gait were seen during obstacle crossing, but this was most evident
      during the Q&A task. Concussed individuals also displayed signs of possible
      instability during the Q&A task. The question and answer task was most sensitive
      to distinguishing concussed individuals from healthy individuals, supporting the
      use of a similar dual-task modality in future testing after concussion to
      determine a proper time for return to activity.

PMID- 16787747
TI  - Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents.
AB  - The weak hydrosolubility of betulinic acid (3) hampers the clinical development
      of this natural anticancer agent. In order to circumvent this problem and to
      enhance the pharmacological properties of betulinic acid (3) and the lupane-type
      triterpenes lupeol (1), betulin (2), and methyl betulinate (7), glycosides (beta
      D-glucosides, alpha-L-rhamnosides, and alpha-D-arabinosides) were synthesized and
      in vitro tested for cytotoxicity against three cancerous (A-549, DLD-1, and B16
      F1) and one healthy (WS1) cell lines. The addition of a sugar moiety at the C-3
      or C-28 position of betulin (2) resulted in a loss of cytotoxicity. In contrast,
      the 3-O-beta-D-glucosidation of lupeol (1) improved the activity by 7- to 12-fold
      (IC50 14-15.0 microM). Moreover, the results showed that cancer cell lines are 8-
      to 12-fold more sensitive to the 3-O-alpha-L-rhamnopyranoside derivative of
      betulinic acid (IC50 2.6-3.9 microM, 22) than the healthy cells (IC50 31 microM).
      Thus, this study indicates that 3-O-glycosides of lupane-type triterpenoids
      represent an interesting class of potent in vitro cytotoxic agents.

PMID- 16787748
TI  - Relative contribution of intracellular and extracellular Ca2+ to alpha2
      adrenoceptor-mediated contractions of ovine pulmonary artery.
AB  - We have examined the mechanism of contractions elicited by guanfacine, a
      selective agonist for alpha(2A/D)-adrenoceptors and its modulations by cyclic
      nucleotides in isolated ovine resistance intra-pulmonary artery. Guanfacine (10
      nM-30 microM) produced concentration-dependent contraction of the pulmonary
      artery rings mounted for isometric recording. Yohimbine (0.1 microM), a
      nonspecific alpha(2)-adrenoceptor antagonist caused a parallel shift to the right
      (1.2 log unit) in the concentration-response curve of guanfacine without
      depressing the maxima. Preincubation of the tissues with Ca(2+)-free solution
      (EGTA 1mM) for 30 min caused a rightward shift (0.8 log unit) of the
      concentration-response curve of guanfacine with the inhibition of the maxima by
      30+/-4.6%. L-type calcium channel blocker, nifedipine (1 microM) slightly
      inhibited (20%) the maximal contraction elicited with guanfacine (10 microM). On
      the other hand, brief exposure to cyclopiazonic acid (10 microM), an inhibitor of
      IP3-sensitive sarcoplasmic reticulum Ca(2+)-ATPase, resulted in marked inhibition
      of concentration-dependent contractions elicited with guanfacine (10 nM-30
      microM), with the maxima being inhibited by 51+/-3.11%. In addition, agents that
      increase intracellular cAMP and cGMP suppressed guanfacine-induced contractions.
      The results of the present study suggest that alpha(2)-adrenoceptor-mediated
      contractions in ovine resistance pulmonary artery is primarily dependent on
      intracellular Ca(2+) with a small contribution from Ca(2+)-influx through voltage
      dependent L-type calcium channels.

PMID- 16787749
TI  - Evolution of cancer stem cells.
AB  - Cancer as a disease driven by cancer stem cells is a concept that has emerged
      over the last few years. However, several issues relating to this phenomenon as
      yet remain unaddressed. A fundamental question is one relating to the
      identification of events leading to transformation of a normal tissue stem cell
      to a cancer stem cell. Complete knowledge of this evolutionary process may be
      crucial for the development of novel effective therapies that influence patient
      prognosis. The scope of this review is to discuss reports that have begun to
      elucidate stem cell transformation either as an isolated event or as a
      progression as an attempt towards understanding some of the critical events
      involved in the process.

PMID- 16787750
TI  - Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003-
      a side effect associated to VPA-therapy not only in young children.
AB  - Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well
      tolerated. Rare serious complications may occur in some patients, including
      haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity
      and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy
      are impaired consciousness, sometimes marked EEG background slowing, increased
      seizure frequency, with or without hyperammonemia. There is still no proof of
      causative effect of VPA in patients with encephalopathy, but only of an
      association with an assumed causal relation. We report 19 patients with VPA
      associated encephalopathy in Germany from the years 1994 to 2003, none of whom
      had been published previously.

PMID- 16787751
TI  - Seizure outcome after surgery for epilepsy due to focal cortical dysplastic
      lesions.
AB  - Neocortical development is a highly complex process encompassing cellular
      proliferation, neuronal migration and cortical organization. At any time this
      process can be interrupted or modified by genetic or acquired factors causing
      malformations of cortical development (MCD). Epileptic seizures are the most
      common type of clinical manifestation, besides developmental delay and focal
      neurological deficits. Seizures due to MCD are frequently pharmacoresistant,
      especially those associated to focal cortical dysplasia (FCD). Surgical therapy
      results have been reported since 1971, however, currently available data from
      surgical series are still limited, mainly due to small number of patients,
      distinct selection of candidates and surgical strategies, variable pathological
      diagnosis and inadequate follow-up. This study addresses the possibilities of
      seizure relief following resection of focal cortical dysplasia, and the impact of
      presurgical evaluation, extent of resection and pathological findings on surgical
      outcome. We included 41 patients, 22 adults and 19 children and adolescents, with
      medically intractable seizures operated on from 1996 to 2002. All were submitted
      to standardized presurgical evaluation including high-resolution MRI, Video-EEG
      monitoring and ictal SPECT. Post-surgical seizure outcome was classified
      according to Engel's schema. Univariate and multivariate analysis were performed.
      Fifteen patients had temporal and 26 extratemporal epilepsies. Of the total 26
      patients (63.4%) reached seizure-free status post-operatively. There was no
      correlation between outcome and age at surgery, duration of epilepsy, frequency
      of seizures, and pathological findings. There was, however, a clear correlation
      with topography of FCD (temporal versus extratemporal) and regional ictal EEG
      onset, on univariate as well as multivariate analysis.

PMID- 16787752
TI  - Determination of in-vivo articular cartilage contact areas of human talocrural
      joint under weightbearing conditions.
AB  - OBJECTIVE: The knowledge of in-vivo cartilage contact biomechanics is important
      to the understanding of the pathogenesis of joint diseases such as
      osteoarthritis. This study investigated the in-vivo contact areas of human
      talocrural joint under weightbearing conditions that simulated the stance phase
      of walking using a combined magnetic resonance (MR) and dual-orthogonal
      fluoroscopic imaging technique. DESIGN: Nine healthy ankles of living subjects
      were recruited for this study. The in-vivo talocrural joint positions were
      recorded using the dual-orthogonal fluoroscopic images at three ankle positions
      that simulated those occurring during the stance phase of walking: heel strike,
      mid-stance, and toe off. Three-dimensional (3D) models of the talocrural joints
      were created from MR images and used to reproduce the in-vivo ankle positions
      recorded on the fluoroscopic images. The talocrural cartilage contact area was
      defined as the overlap area of the distal tibial and the proximal talar cartilage
      surfaces. The method was validated using an in-vitro experimental setup to
      evaluate its accuracy in determination of cartilage contact area. RESULTS: The
      validation study demonstrated that the articular cartilage contact area of the
      talocrural joint determined using the imaging technique was approximately 4%
      lower than that of the experimental measurement. In the nine living ankles, the
      average cartilage coverage area was 964.9+/-156.1 mm(2) on the distal tibia and
      1304.8+/-208.4 mm(2) on the proximal talus. The average talocrural cartilage
      contact areas were 272.7+/-61.1 mm(2) at heel strike, 416.8+/-51.7 mm(2) at mid
      stance, and 335.7+/-64.5 mm(2) at toe off. The contact area at mid-stance was
      significantly larger than those at heel strike and toe off, while the contact
      area at toe off was significantly larger than that at heel strike. CONCLUSION:
      The combined dual fluoroscopic and MR imaging technique was shown to be capable
      of determining in-vivo talocrural cartilage contact areas. During the simulated
      stance phase of walking, the contact areas were less than 44% and 31% of the
      cartilage coverage areas of the distal tibia and the proximal talus,
      respectively. These data may be useful for understanding in-vivo biomechanical
      function of the cartilage as well as the etiology of osteoarthritis.

PMID- 16787753
TI  - Algal toxin yessotoxin signalling pathways involve immunocyte mussel calcium
      channels.
AB  - A fragment of a putative L-type Ca(2+) channel has been identified by molecular
      biology experiments in immunocytes from the mussel Mytilus galloprovincialis.
      Using the cell permeable and Ca(2+)-specific fluorochrome FURA 2-AM, we have
      demonstrated that the algal toxin yessotoxin (YTX) is able to increase
      intracellular Ca(2+) concentration in M. galloprovincialis immunocytes. The YTX
      effect on Ca(2+) increase is inhibited by the L-type Ca(2+) channel inhibitor,
      verapamil, which is cAMP- and cGMP-dependent, but PKA- and nitric oxide
      independent. On the basis of these observations, a possible role for YTX as a
      potential disturber of mussel immune efficiency is suggested.

PMID- 16787754
TI  - Bacteremia in children at a regional hospital in Trinidad.
AB  - OBJECTIVE: The objective of this study was to provide a Trinidadian perspective
      on pediatric community-acquired and hospital-acquired bacteremia via the
      documentation of common etiologic agents, antimicrobial profiles of the isolated
      pathogens, and patient outcome. METHODS: This was a six-year retrospective study
      of children with bacteremia admitted to the pediatric wards of the San Fernando
      General Hospital, Trinidad. RESULTS: Seven hundred and four episodes of pediatric
      bacteremia were reviewed during the six-year study period. The predominant
      isolate was Staphylococcus aureus (23.9%), followed by Pseudomonas aeruginosa
      (15.5%), Klebsiella pneumoniae (12.5%), and Enterobacter spp (11.1%). The
      remaining isolates each accounted for less than 10% of total isolates. The
      mortality rate was highest for P. aeruginosa (39.4%), Streptococcus pneumoniae
      (22.5%), and Escherichia coli (19.2%). Of the six cases due to Neisseria
      meningitidis, only two survived. The overall mortality rate for the study period
      was 15.1%, but varied considerably according to age. All deaths due to P.
      aeruginosa and E. coli occurred in neonates. Almost 90% and about half of all S.
      aureus were resistant to ampicillin and erythromycin, respectively; nineteen
      (11.3%) were methicillin-resistant. More than 95% of K. pneumoniae and more than
      87% of Haemophilus influenzae were resistant to ampicillin. Group B streptococci
      were fully susceptible to ampicillin and amoxicillin-clavulanic acid, but showed
      >90% and >70% resistance to tetracycline and trimethoprim-sulfamethoxazole,
      respectively. Of the 40 strains of S. pneumoniae isolated, 10.0% had a minimum
      inhibitory concentration (MIC) >or=4 microg/mL (resistance) and 12.5% had a
      MIC=2.0 microg/mL (intermediate resistance) to ceftriaxone, while 7.5% showed
      intermediate resistance (MIC between 0.12 and 1 microg/mL) and 25.0% showed
      resistance (MIC >or=2 microg/mL) to penicillin. CONCLUSION: The bacteremia rate
      was found to be 8.4% among hospitalized children suspected of having sepsis and
      from whom a blood culture was positive. Bacteremia was also associated with a
      high mortality rate of 15.1%. An unusually high level of bacteremia with Gram
      negative enteric bacteria was seen, which might indicate cross infection and
      reflect a breakdown in infection control measures. Relatively high-level
      resistance of S. pneumoniae to penicillin and ceftriaxone was not seen, even
      though the overall prevalence of resistance to other antibiotics among other
      pathogens was relatively low. The drugs that showed the greatest efficacy were
      imipenem, gentamicin, ciprofloxacin, and the cephalosporins ceftazidime and
      ceftriaxone.

PMID- 16787755
TI  - Correspondence to Creydt VP et al., Cytotoxic effect of Shiga toxin-2 holotoxin
      and its B subunit on human renal tubular epithelial cells, Microbes Infect. 8(2)
      (2006) 410-419.

PMID- 16787756
TI  - Temporal analysis of French Bordetella pertussis isolates by comparative whole
      genome hybridization.
AB  - Bordetella pertussis, a gram-negative beta-proteobacterium, is the agent of
      whooping cough in humans. Whooping cough remains a public health problem
      worldwide, despite well-implemented infant/child vaccination programs. It
      continues to be endemic and is observed cyclically in vaccinated populations.
      Classical molecular subtyping methods indicate that genome diversity among B.
      pertussis isolates is limited. Although the whole bacterial genome has been
      studied by pulsed-field gel electrophoresis, the genes implicated in the
      diversity have not been identified. We developed a B. pertussis whole-genome DNA
      microarray representing over 91% of the predicted coding sequences of the
      sequenced strain Tohama I. Genomic DNA from clinical isolates with various pulsed
      field gel electrophoresis profile patterns was competitively hybridized with the
      DNA microarray and coding sequences were classified as present, absent or
      duplicated. Our data strongly suggest that the B. pertussis population is
      dynamic. In France, with highly vaccinated population, the genetic diversity is
      low and decreasing with time, and clonal expansion correlates with cycles of the
      disease. This decrease in diversity is essentially due to loss of genes and
      pseudogenes. The genes deleted are most of the time flanked by insertion
      sequences.

PMID- 16787757
TI  - Both alpha-haemolysin determinants contribute to full virulence of uropathogenic
      Escherichia coli strain 536.
AB  - Uropathogenic Escherichia coli strain 536 possesses two intact copies of the
      alpha-haemolysin determinant localised on distinct pathogenicity islands. The
      coding regions of the two hlyCABD operons are conserved; however, upstream
      sequences are entirely dissimilar. Consequently, expression of the encoded toxin
      molecules in vitro is highly different. On the other hand, the contribution of
      the individual determinants to the strain's virulence is the same. Isogenic
      mutants lacking individual hly determinants have a similar increase in LD50 value
      in a mouse model of urinary tract infection. Mouse lung toxicity as well as in
      vitro assays reveals a significant decrease in acute cytotoxicity of both mutants
      in comparison to the parent wild-type strain; however, the two hly mutants do not
      significantly differ from each other in these respects. Single channel recordings
      show no difference in electrophysiological characteristics of the pores formed by
      the individual HlyA molecules on synthetic planar lipid membranes. Nor do the
      paralogues have any target cell preference in an in vitro cytotoxicity assay. Our
      data suggest that the two hly paralogues encode identical toxin functions;
      however, due to different regulation of expression, they participate at distinct
      stages of the infectious process. Interestingly, the unrelated uropathogenic E.
      coli strain J96 shares the same two hly alleles, suggesting that acquisition of
      the two paralogues accorded a selective evolutionary advantage.

PMID- 16787759
TI  - Experiences of engineering Grid-based medical software.
AB  - OBJECTIVES: Grid-based technologies are emerging as potential solutions for
      managing and collaborating distributed resources in the biomedical domain. Few
      examples exist, however, of successful implementations of Grid-enabled medical
      systems and even fewer have been deployed for evaluation in practice. The
      objective of this paper is to evaluate the use in clinical practice of a Grid
      based imaging prototype and to establish directions for engineering future
      medical Grid developments and their subsequent deployment. METHOD: The MammoGrid
      project has deployed a prototype system for clinicians using the Grid as its
      information infrastructure. To assist in the specification of the system
      requirements (and for the first time in healthgrid applications), use-case
      modelling has been carried out in close collaboration with clinicians and
      radiologists who had no prior experience of this modelling technique. A critical
      qualitative and, where possible, quantitative analysis of the MammoGrid prototype
      is presented leading to a set of recommendations from the delivery of the first
      deployed Grid-based medical imaging application. RESULTS: We report critically on
      the application of software engineering techniques in the specification and
      implementation of the MammoGrid project and show that use-case modelling is a
      suitable vehicle for representing medical requirements and for communicating
      effectively with the clinical community. This paper also discusses the practical
      advantages and limitations of applying the Grid to real-life clinical
      applications and presents the consequent lessons learned. CONCLUSIONS: The work
      presented in this paper demonstrates that given suitable commitment from
      collaborating radiologists it is practical to deploy in practice medical imaging
      analysis applications using the Grid but that standardization in and stability of
      the Grid software is a necessary pre-requisite for successful healthgrids. The
      MammoGrid prototype has therefore paved the way for further advanced Grid-based
      deployments in the medical and biomedical domains.

PMID- 16787760
TI  - Antibodies from patients with dengue viral infection mediate cellular
      cytotoxicity.
AB  - Acute and late convalescent sera (collected at day 5 of disease onset and 1 year
      later) from dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome
      (DHF/DSS) laboratory confirmed cases, were tested for antibody-dependent cell
      mediated cytotoxicity (ADCC) activity using dengue 1 (DENV-1) or dengue 2 (DENV
      2) infected cells as target. All patients experienced their first dengue virus
      (DENV) infection 20 years before. ADCC activity was detected in acute sera from
      DHF/DSS but not in sera from DF patients. However, 1 year after illness, ADCC
      activity was observed in all cases. This preliminary report represents one of the
      few studies of ADCC in dengue patients and suggests that ADCC could be implicated
      in dengue pathogenesis.

PMID- 16787761
TI  - Effectiveness of 1% diclofenac gel in the treatment of wrist extensor
      tenosynovitis in long distance kayakers.
AB  - Anecdotally many athletes use non-steroidal anti-inflammatory gels during
      competition to allow continued participation. To determine if this clinical
      practice is useful a randomised placebo-controlled study was conducted at the 5
      day 2004 Red Cross Murray River Marathon. Forty-two kayakers presented with wrist
      extensor tenosynovitis while competing in the single and double kayak events. All
      subjects received standard treatment of ice, stretches and massage for wrist
      tenosynovitis before being randomised into a placebo or 1% diclofenac gel group.
      Evaluation was done by using a visual analogue scale (0-10) for pain and by
      clinical grading (0-3). The main outcome measurements were reduction in pain and
      clinical grading, the requirement for a rescue medication (paracetamol or
      diclofenac tablets) and effect on performance times. Both groups had similar pain
      scores and clinical grading on the first and fifth days of pain. On the second to
      fourth days of pain there was clearly no benefit and possibly a detrimental
      effect on pain with diclofenac gel relative to placebo. However, diclofenac
      tablets were possibly beneficial for pain relative to paracetamol tablets. The
      effects of pain and the various treatments on performance time were either
      trivial (<0.5%) or small, but none was particularly clear. We conclude that
      standard treatment appears to be sufficient for the management of wrist extensor
      tenosynovitis during competition.

PMID- 16787763
TI  - On the origin of avian air sacs.
AB  - For many vertebrates the lung is the largest and lightest organ in the body
      cavity and for these reasons can greatly affect an organism's shape, density, and
      its distribution of mass; characters that are important to locomotion. In this
      paper non-respiratory functions of the lung are considered along with data on the
      respiratory capacities and gas exchange abilities of birds and crocodilians to
      infer the evolutionary history of the respiratory systems of dinosaurs, including
      birds. From a quadrupedal ancestry theropod dinosaurs evolved a bipedal posture.
      Bipedalism is an impressive balancing act, especially for tall animals with
      massive heads. During this transition selection for good balance and agility may
      have helped shape pulmonary morphology. Respiratory adaptations arising for
      bipedalism are suggested to include a reduction in costal ventilation and the use
      of cuirassal ventilation with a caudad expansion of the lung into the dorsal
      abdominal cavity. The evolution of volant animals from bipeds required yet again
      a major reorganization in body form. With this transition avian air sacs may have
      been favored because they enhanced balance and agility in flight. Finally, I
      propose that these hypotheses can be tested by examining the importance of the
      air sacs to balance and agility in extant animals and that these data will
      enhance our understanding of the evolution of the respiratory system in
      archosaurs.

PMID- 16787762
TI  - Electrochemical oxidation of morin and interaction with DNA.
AB  - A poly (tetrafluroethylene)-deoxyribonucleate acid (PTFE-DNA) film-modified
      glassy carbon electrode (GCE) has been fabricated. The electrochemical oxidation
      behaviors of morin as well as its interaction with DNA have been studied at PTFE
      DNA film-modified GCE and bare GCE by electrochemical methods. This modified
      electrode shows an enhanced effectiveness towards the oxidation of morin.
      Importantly, as to the interaction between morin and DNA in solution,
      characteristic parameters such as the binding stoichiometry and association
      equilibrium constant according to the Hill model for cooperative binding have
      been determined on the basis of linear sweep voltammetry and chronocoulometry.

PMID- 16787764
TI  - Faecal sterols determination in wastewater and surface water.
AB  - A simplified method to detect faecal sterols, as an alternative assessment of
      environmental faecal pollution is proposed. The aim of this study is the
      development of a method to determine sterols in water samples avoiding sample
      filtration through glass fibre filter. The method is based on a liquid-liquid
      extraction and a final GC-FID determination. The quantified sterols are
      coprostanol and 24-ethylcoprostanol, while 5alpha-cholestane is used as internal
      standard. The recovery of coprostanol and 24-ethylcoprostanol in wastewater
      ranges from 90 to 100% and the detection limit is 1-2 microgl(-1). Moreover the
      method proved to be useful for the sterols determination in surface water too.

PMID- 16787765
TI  - A new method for determination of plasma homocystine by isotope dilution and
      electrospray tandem mass spectrometry.
AB  - A new analytical determination method of homocystine in human plasma has been
      developed. The method utilises liquid chromatography coupled to ionspray tandem
      mass spectrometry. Quantitative analysis was achieved using as an internal
      standard homocystine-d8. Mass spectrometer operated in the multiple reaction
      mode: homocystine and homocystine-d8 were detected through the transition from
      the precursor to the product ion (from m/z 269.3 to 90.0, and m/z 277.3 to 94.0,
      respectively). The method is extremely sensitive, with limit of detection in the
      range of 6 fmol/L. The interassay and intraassay coefficients of variation for
      homocystine were 6.22% and 3.4%, respectively. The accuracy for the added
      homocystine ranged from 85% to 110%. High specificity of tandem mass spectrometry
      coupled with a fast chromatographic process is suitable for a rapid and reliable
      assay of homocystine.

PMID- 16787766
TI  - Structural features in carrageenan that interact with a heparin-binding
      hematopoietic growth factor and modulate its biological activity.
AB  - The effects of carrageenans' structural features on its interaction with
      granulocyte colony-stimulating factor (G-CSF) and on the growth and
      differentiation of a G-CSF dependent leukemia cell line (NFS-60) were studied.
      lambda, iota, and kappa carrageenans, with decreasing contents of sulfation,
      bound to G-CSF with binding constants of (6.2+/-0.6) x 10(5)M(-1), (7.4+/-0.5) x
      10(5)M(-1) and (6.0+/-0.4) x 10(5)M(-1), and with 27.7+/-0.2, 17.4+/-0.1 and
      8.4+/-0.1 binding sites, respectively. However, kappa carrageenan oligosaccharide
      had no affinity for G-CSF. The three carrageenans significantly inhibited G-CSF
      induced growth of NFS-60 cells. The high sulfate content lambda carrageenan could
      also induce the maturation of the cells, but relatively low sulfate content iota
      and kappa carrageenans could not. The results suggested that G-CSF-carrageenan
      bindings were dependent on carrageenans' sulfate contents and chain lengths,
      which could also affect the growth and differentiation of NFS-60 cells.

PMID- 16787767
TI  - Solid phase extraction--non-aqueous capillary electrophoresis for determination
      of metformin, phenformin and glyburide in human plasma.
AB  - Solid phase extraction (SPE) was coupled at line to capillary electrophoresis
      (CE) for the determination of three basic and neutral diabetic drugs (metformin,
      phenformin and glyburide) in human plasma. The SPE procedure employed a C(18)
      cartridge to remove most of the water and proteins from the plasma sample.
      Analyte detectability was increased due to trace enrichment during the SPE
      process. Elution of metformin, phenformin and glyburide was achieved with
      methanol+3% acetic acid. CE analysis was performed using a non-aqueous buffer,
      acetonitrile+5mM ammonium acetate+5% acetic acid, which afforded rapid separation
      of metformin from phenformin within 3 min. Glyburide, with a migration time
      longer than 6 min, did not cause any interference. The present SPE-CE method,
      with an electrokinetic injection time of 6s and UV detection at 240 nm, was
      useful for monitoring down to 1 microg/mL of metformin and phenformin in human
      plasma. When the electrokinetic injection time was increased to 36s, the
      detection limits were improved to 12 ng/mL for metformin and 6 ng/mL for
      phenformin.

PMID- 16787768
TI  - The pH-dependence of amide chemical shift of Asp/Glu reflects its pKa in
      intrinsically disordered proteins with only local interactions.
AB  - Detailed knowledge of the pH-dependence of ionizable residues in both folded and
      unfolded states of proteins is essential to understand the role of electrostatics
      in protein folding and stability. The reassembly of E. coli Thioredoxin (Trx) by
      complementation of its two disordered fragments (1-37/38-108) provides a folded
      heterodimer in equilibrium with its unfolded state which, based on circular
      dichroism and NMR spectroscopy, consists of two unfolded monomers. To gain
      insight into the role of electrostatics in protein folding and stability, we
      compared the pH-dependence of the carboxylate sidechain chemical shift of each
      Asp/Glu against that of its backbone amide chemical shift in the unfolded
      heterodimer. We monitored via C(CO)NH experiments four Asp and four Glu in
      fragments 38 to 108 (C37) of Trx in the pH range from 2.0 to 7.0 and compared
      them with results from (1)H(15)N HSQC experiments [Pujato et al., Biophys. J., 89
      (2005) 3293-3302]. The (1)H(15)N HSQC analysis indicates two segments with quite
      distinct behavior: (A) a segment from Ala57 to Ala108 in which ionizable residues
      have up to three contiguous neighbors with pH-dependent backbone amide shifts,
      and (B) a segment of fifteen contiguous pH-dependent backbone amide shifts (Leu42
      to Val56) in which two Asp and two Glu are implicated in medium range
      interactions. In all cases, the titration curves are simple modified sigmoidals
      from which a pH-midpoint (pH(m)) can be obtained by fitting. In segment A, the
      pH(m) of a given backbone amide of Asp/Glu mirrors within 0.15 pH-units that of
      its carboxylate sidechain (i.e., the pK(a)). In contrast, segment B shows
      significant differences with absolute values of 0.46 and 0.74 pH-units for Asp
      and Glu, respectively. The dispersion in the pH(m) of the backbone amide of
      Asp/Glu is also different in the two segments. Segment A shows a dispersion of
      0.31 and 0.17 pH-units for Asp and Glu, respectively. Segment B shows a
      substantially larger dispersion (0.50 and 1.08 pH-units for Asp and Glu,
      respectively). In both segments, the dispersion in the pH(m) of its backbone
      amide is larger than in the pK(a) of the carboxylate sidechain (the latter is
      only 0.17 and 0.52 pH-units for Asp and Glu, respectively). Our results indicate
      that the pH(m) of the backbone amide chemical shift of Asp/Glu in a disordered
      polypeptide segment is a good predictor of its pK(a) whenever there are none or
      few neighboring backbone amides with similar pH-dependence.

PMID- 16787769
TI  - Prophylactic and therapeutic use of recombinant activated factor VII in patients
      with cirrhosis and coagulation impairment.
AB  - Patients with cirrhosis and impaired coagulation often pose major therapeutic
      problems during bleeding episodes or invasive procedures. Recombinant activated
      factor VII (rFVIIa), which has been licensed for the treatment of haemophilia
      patients with factor VIII or IX inhibitors, has been occasionally used in
      cirrhotic patients. We present five patients with cirrhosis and coagulopathy who
      received 1-4 recombinant activated factor VII infusions either prophylactically
      in order to safely undergo an invasive procedure or therapeutically in order to
      control a severe bleeding episode which did not respond to standard supportive
      care. In particular, recombinant activated factor VII infusions were given in two
      patients before a percutaneous liver biopsy, in one patient before teeth
      extraction and in two patients with haemoperitoneum after an invasive procedure.
      Infusions of recombinant activated factor VII achieved rapid correction of
      prothrombin time in all cases allowing the safe performance of invasive
      procedures or resulting in efficient control of the bleeding episode. In
      conclusion, recombinant activated factor VII seems to be a rather promising agent
      for the prevention or treatment of complications of haemostasis impairment in
      cirrhotic patients. However, its exact role in this setting needs to be evaluated
      within well-designed, controlled clinical trials.

PMID- 16787770
TI  - Abscess in Crohn's disease--the knife may not be necessary (an American view).

PMID- 16787771
TI  - Endoscopic mucosal resection and mucosa ablation with argon-plasma coagulation in
      a high-risk patient with Barrett's oesophagus and oesophageal adenocarcinoma.

PMID- 16787772
TI  - Comparison of low and high frequency transducers in the detection of liver
      metastases.
AB  - BACKGROUND AND AIMS: To evaluate the benefit of the additional use of a high
      frequency ultrasound probe (7.5 MHz) in finding suspicious liver lesions compared
      to the examination using a 3.5-MHz transducer only. PATIENTS AND METHODS: One
      hundred and fifty-seven patients with underlying malignant disease were examined
      with both transducers using one of three ultrasound machines (Siemens Sonoline
      Elegra, GE Healthcare Logic 9, or Hitachi EUB-8500). Findings on hepatic lesions
      were collected on a standardised documentation sheet and evaluated by descriptive
      statistics. RESULTS: Ninety-three patients (59.2% of all patients) showed no
      evident liver lesion on conventional ultrasound with the 3.5 MHz probe. In 29
      patients (18.5%) new suspicious liver lesions were found by using the high
      frequency transducer. Thirteen of these 29 patients (44.8%) were suspected to
      suffer from diffuse infiltration of the liver with malignant lesions or at least
      10 additional visible lesions. In 14 patients, no liver lesion had been known
      before high frequency ultrasound examination. The size of newly described liver
      lesions ranged from 2 mm to 1.5 cm. Time needed for the additional examination
      with the high frequency transducer ranged between 1 and 15 min with an average of
      4.0 min. CONCLUSION: The additional use of a high frequency transducer in
      patients with underlying malignant disease slightly extends the examination time,
      but reveals new, potentially malignant hepatic lesions in almost every fifth
      patient.

PMID- 16787773
TI  - The occurrence of terminal ileal histological abnormalities in patients with
      coeliac disease.
AB  - INTRODUCTION: Coeliac disease causes histological changes throughout the small
      bowel, but is often a proximal lesion. We wanted to assess whether terminal ileal
      histological abnormalities occurred more commonly in patients with coeliac
      disease and if specific assessment of intraepithelial lymphocytes increases the
      recognition of undiagnosed coeliac disease. METHODS: Terminal ileal biopsies were
      prospectively examined over a 3-year period (April 2001-May 2004). Patients were
      included if they were found to have a synchronous duodenal biopsy that gave a new
      diagnosis of coeliac disease (n=20). Terminal ileal biopsies taken at colonoscopy
      during the same period were also examined from four groups of patients: coeliac
      disease established on a gluten-free diet but with persisting symptoms (n=25),
      inflammatory bowel disease (n=47), chronic diarrhoea (n=44) and polyp
      surveillance (n=47). All biopsies were graded according to the Marsh criteria and
      an intraepithelial lymphocytes count per 100 enterocytes was obtained. RESULTS:
      There was only one patient from all five groups who had villous atrophy of the
      terminal ileal. This patient had a new diagnosis of coeliac disease. The mean
      intraepithelial lymphocytes count in the coeliac disease group was 23.7
      intraepithelial lymphocytes/100 enterocytes. This was significantly higher than
      the control groups: coeliac disease on a gluten-free diet=17.5 (p<0.012),
      inflammatory bowel disease=12.3 (p<0.0001), diarrhoea=12.6 (p<0.0001) and
      polyp=13.7 (p<0.0002). Validating terminal ileal villous intraepithelial
      lymphocytes counts as a test for coeliac disease using an intraepithelial
      lymphocytes/100 enterocytes of >25 gives a sensitivity of 45% and a specificity
      of 97.8%. CONCLUSION: Routinely quantifying terminal ileal intraepithelial
      lymphocytes may be of limited clinical value. However, subjective recognition of
      raised intraepithelial lymphocytes on a terminal ileal biopsy should alert the
      clinician to the possibility of coeliac disease.

PMID- 16787774
TI  - Pneumatosis cystoides intestinalis: imaging findings with colonoscopy
      correlation.
AB  - We report on a case of pneumatosis cystoides intestinalis in a 32-year-old woman
      affected by coeliac disease with stool cultures positive for salmonella. After
      plain film of the abdomen, patient underwent computed tomography and magnetic
      resonance colonography studies that demonstrated numerous, diffuse bubblelike
      intramural gas collections into the ascending, transverse and descending colonic
      wall. CT and MR findings were correlated with colonoscopy.

PMID- 16787776
TI  - Controlling quaternary structure assembly: subunit interface engineering and
      crystal structure of dual chain avidin.
AB  - Dual chain avidin (dcAvd) is an engineered avidin form, in which two circularly
      permuted chicken avidin monomers are fused into one polypeptide chain. DcAvd can
      theoretically form two different pseudotetrameric quaternary assemblies because
      of symmetry at the monomer-monomer interfaces. Here, our aim was to control the
      assembly of the quaternary structure of dcAvd. We introduced the mutation I117C
      into one of the circularly permuted domains of dcAvd and scanned residues along
      the 1-3 subunit interface of the other domain. Interestingly, V115H resulted in a
      single, disulfide locked quaternary assembly of dcAvd, whereas I117H could not
      guide the oligomerisation process even though it stabilised the protein. The
      modified dcAvd forms were found to retain their characteristic pseudotetrameric
      state both at high and low pH, and were shown to bind D-biotin at levels
      comparable to that of wild-type chicken avidin. The crystal structure of dcAvd
      biotin complex at 1.95 Angstroms resolution demonstrates the formation of the
      functional dcAvd pseudotetramer at the atomic level and reveals the molecular
      basis for its special properties. Altogether, our data facilitate further
      engineering of the biotechnologically valuable dcAvd scaffold and gives insights
      into how to guide the quaternary structure assembly of oligomeric proteins.

PMID- 16787775
TI  - Structural characterization of Set1 RNA recognition motifs and their role in
      histone H3 lysine 4 methylation.
AB  - The yeast Set1 histone H3 lysine 4 (H3K4) methyltransferase contains, in addition
      to its catalytic SET domain, a conserved RNA recognition motif (RRM1). We present
      here the crystal structure and the secondary structure assignment in solution of
      the Set1 RRM1. Although RRM1 has the expected betaalphabetabetaalphabeta RRM
      fold, it lacks the typical RNA-binding features of these modules. RRM1 is not
      able to bind RNA by itself in vitro, but a construct combining RRM1 with a newly
      identified downstream RRM2 specifically binds RNA. In vivo, H3K4 methylation is
      not affected by a point mutation in RRM2 that preserves Set1 stability but
      affects RNA binding in vitro. In contrast mutating RRM1 destabilizes Set1 and
      leads to an increase of dimethylation of H3K4 at the 5'-coding region of active
      genes at the expense of trimethylation, whereas both, dimethylation decreases at
      the 3'-coding region. Taken together, our results suggest that Set1 RRMs bind
      RNA, but Set1 RNA-binding activity is not linked to H3K4 methylation.

PMID- 16787777
TI  - Extended substrate recognition in caspase-3 revealed by high resolution X-ray
      structure analysis.
AB  - Caspases are cysteine proteases involved in the signalling cascades of programmed
      cell death in which caspase-3 plays a central role, since it propagates death
      signals from intrinsic and extrinsic stimuli to downstream targets. The atomic
      resolution (1.06 Angstroms) crystal structure of the caspase-3 DEVD-cmk complex
      reveals the structural basis for substrate selectivity in the S4 pocket. A low
      barrier hydrogen bond is observed between the side-chains of the P4 inhibitor
      aspartic acid and Asp179 of the N-terminal tail of the symmetry related p12
      subunit. Site-directed mutagenesis of Asp179 confirmed the significance of this
      residue in substrate recognition. In the 1.06 Angstroms crystal structure, a
      radiation damage induced rearrangement of the inhibitor methylketone moiety was
      observed. The carbon atom that in a substrate would represent the scissile
      peptide bond carbonyl carbon clearly shows a tetrahedral coordination and
      resembles the postulated tetrahedral intermediate of the acylation reaction.

PMID- 16787778
TI  - The crystal structure of the transthyretin-like protein from Salmonella dublin, a
      prokaryote 5-hydroxyisourate hydrolase.
AB  - The mechanism of binding of thyroid hormones by the transport protein
      transthyretin (TTR) in vertebrates is structurally well characterised. However, a
      homologous family of transthyretin-like proteins (TLPs) present in bacteria as
      well as eukaryotes do not bind thyroid hormones, instead they are postulated to
      perform a role in the purine degradation pathway and function as 5
      hydroxyisourate hydrolases. Here we describe the 2.5 Angstroms X-ray crystal
      structure of the TLP from the Gram-negative bacterium Salmonella dublin, and
      compare and contrast its structure with vertebrate TTRs. The overall architecture
      of the homotetramer is conserved and, despite low sequence homology with
      vertebrate TTRs, structural differences within the monomer are restricted to
      flexible loop regions. However, sequence variation at the dimer-dimer interface
      has profound consequences for the ligand binding site and provides a structural
      rationalisation for the absence of thyroid hormone binding affinity in bacterial
      TLPs: the deep, negatively charged thyroxine-binding pocket that characterises
      vertebrate TTR contrasts with a shallow and elongated, positively charged cleft
      in S. dublin TLP. We have demonstrated that Sdu_TLP is a 5-hydroxyisourate
      hydrolase. Furthermore, using site-directed mutagenesis, we have identified three
      conserved residues located in this cleft that are critical to the enzyme
      activity. Together our data reveal that the active site of Sdu_TLP corresponds to
      the thyroxine binding site in TTRs.

PMID- 16787779
TI  - Probing nature's knots: the folding pathway of a knotted homodimeric protein.
AB  - The homodimeric protein YibK from Haemophilus influenzae belongs to a recently
      discovered superfamily of knotted proteins that has brought about a new protein
      folding conundrum. Members of the alpha/beta-knot clan form deep trefoil knots in
      their native backbone structure, a topological feature that is currently
      unexplained in the protein-folding field. To help solve the puzzle of how a
      polypeptide chain can efficiently knot itself, the folding kinetics of YibK have
      been studied extensively and the results are reported here. Folding was monitored
      using probes for changes in both secondary and tertiary structure, and the
      monomer-dimer equilibrium was perturbed with a variety of solution conditions to
      allow characterisation of otherwise inaccessible states. Multiphasic kinetics
      were observed in the unfolding and refolding reactions of YibK, and under
      conditions where the dimer is favoured, dissociation and association were rate
      limiting, respectively. A folding model consistent with all kinetic data is
      proposed: YibK appears to fold via two parallel pathways, partitioned by proline
      isomerisation events, to two distinct monomeric intermediates. These form a
      common third intermediate that is able to fold to native dimer. Kinetic
      simulations suggest that all intermediates are on-pathway. These results provide
      the valuable groundwork required to further understand how Nature codes for knot
      formation.

PMID- 16787780
TI  - Electrostatic interactions in the denatured state and in the transition state for
      protein folding: effects of denatured state interactions on the analysis of
      transition state structure.
AB  - The development of electrostatic interactions during the folding of the N
      terminal domain of the ribosomal protein L9 (NTL9) is investigated by pH
      dependent rate equilibrium free energy relationships. We show that Asp8, among
      six acidic residues, is involved in non-native, electrostatic interactions with
      K12 in the transition state for folding as well as in the denatured state. The
      perturbed native state pK(a) of D8 (pK(a) = 3.0) appears to be maintained through
      non-native interactions in both the transition state and the denatured state.
      Mutational effects on the stability of the transition state for protein
      (un)folding are often analyzed in respect to change in ground states. Thus, the
      interpretation of transition state analysis critically depends on an
      understanding of mutational effects on both the native and denatured state.
      Increasing evidence for structurally biased denatured states under physiological
      conditions raises concerns about possible denatured state effects on folding
      studies. We show that the structural interpretation of transition state analysis
      can be altered dramatically by denatured state effects.

PMID- 16787782
TI  - Stages of wound healing and their clinical relevance.
AB  - Wound healing describes the host mechanisms involved in the process of restoring
      the continuity of tissues after injury. Wound healing progresses through a
      continuum of overlapping stages characterized by macroscopic, microscopic, and
      biochemical events. An understanding of the relation between these events can
      enhance clinicians' skills in wound management.

PMID- 16787784
TI  - Management of hard-to-heal wounds.
AB  - Some wounds do not heal normally and present the practitioner with a challenge.
      These can be thought of as hard-to-heal wounds. There are numerous causes of such
      wounds, and when they occur, the veterinarian should consider all factors
      associated with the wound. When diagnostic tests are indicated, they should be
      performed. Finally, appropriate measures should be taken to correct the
      underlying cause of the hard-to-heal wound.

PMID- 16787785
TI  - Initial wound management.
AB  - A wounded patient can be presented to the veterinary surgeon under a number of
      circumstances. The wound could result from external trauma,such as vehicle trauma
      or an animal fight, or it could have been created by surgical intervention, such
      as the removal of a mass. A wound could also be secondary to a failed initial
      attempt at wound closure. No matter what the cause, initial wound management
      often follows similar pathways. A successful wound closure and healing outcome is
      often dependent on adherence to basic principles of wound assessment, appropriate
      care, and reassessment. This article covers the approach to and specific options
      for the initial stages of wound management.

PMID- 16787783
TI  - Differences in cutaneous wound healing between dogs and cats.
AB  - Regardless of the species involved, wound healing follows a predictable course of
      overlapping phases. In spite of these commonalities, significant species
      differences in cutaneous wound healing have been uncovered in the Equidae and,
      more recently, between the dog and cat. It has also recently been shown that the
      subcutaneous tissues play an important supporting role in cutaneous wound
      healing, which may help to ex-plain healing differences between cats and dogs.
      These discoveries may improve veterinarians' understanding of problem wound
      healing in the cat and, hopefully, lead to better strategies for wound management
      in this sometimes troublesome species.

PMID- 16787786
TI  - Topical and systemic medications for wounds.
AB  - There are a plethora of topical and systemic medications available to the
      veterinary practitioner today that aid the wound healing process. Some of these
      help to maintain a moist environment. Others increase growth factors, provide
      local energy sources, control infection, provide for debridement, increase wound
      blood flow and temperature, or reduce wound edema. Modern wound care requires
      that the proper products(s)be used, depending on the condition of the wound and
      the phase of wound healing. This article discusses various wound care products
      and provides guidelines on their use.

PMID- 16787787
TI  - Dressings, bandages, and splints for wound management in dogs and cats.
AB  - New materials have allowed the role of the bandage to expand from passive
      protector to active participant in the wound healing process. By building a
      bandage that maintains a moist wound environment,the veterinarian uses the
      patient's own wound healing mechanisms to provide selective autolytic
      debridement, speed granulation and epithelialization, decrease infection, and
      increase patient comfort. A large variety of primary dressings are available to
      custom-make a bandage appropriate to each stage of wound healing. This article
      discusses the principles of moist wound healing, selection and application of
      primary dressings, special considerations for applying and changing bandages and
      splints, and prevention of bandage complications.

PMID- 16787788
TI  - Head and facial wounds in dogs and cats.
AB  - Injuries to the head and facial area are common in small animal surgery. Although
      many of the injuries at first may seem formidable, most can be repaired using
      basic reconstructive surgery procedures. The excel-lent blood supply in this area
      and the availability of local tissues provide many options for repairing most
      wounds. This article describes the indications and techniques for reconstructing
      wounds in this area.

PMID- 16787789
TI  - Distal limb and paw injuries.
AB  - Distal limb reconstruction is complicated by the paucity of local tissues and the
      frequent association of orthopedic injury with cutaneous loss. Second-intention
      healing or skin stretching techniques are used for wounds involving less than a
      30% circumference of the limb. Skin grafts are recommended for reconstruction of
      larger superficial wounds after establishing a bed of granulation tissue or for
      immediate reconstruction of clean wounds overlying healthy muscle. Wounds
      complicated by orthopedic injury benefit from early reconstruction using
      vascularized tis-sue. Weight-bearing surface reconstruction and management of
      partial amputation injuries are functionally difficult because of the
      environmental stress placed on the paw pads. Paw pad grafts, paw pad
      transposition techniques, centralization of digits, and microvascular free tissue
      trans-fer of paw pads can be considered for weight-bearing surface
      reconstruction. Definitive guidelines describing when each of these techniques
      should be used have not been established.

PMID- 16787790
TI  - Large trunk wounds.
AB  - Management of large trunk wounds begins with good wound management and bandaging.
      When a healthy wound bed exists and adequate tissue is present, the wound is
      closed. Fortunately, there is an abundance of loose trunk skin in most animals,
      and wound closure can be accomplished by simple reconstructive techniques, such
      as undermining and tension or "walking sutures." Nevertheless, some wounds and
      areas of the torso may require more advanced tension-relieving techniques, skin
      stretching, and tissue implants or flaps to achieve tension-free closure and
      successful wound healing. Use of these techniques allows wound closure and good
      cosmetic results for even those wounds that initially may seem foreboding.

PMID- 16787791
TI  - Bullet, bite, and burn wounds in dogs and cats.
AB  - Veterinarians are frequently presented with bullet, bite, or burn trauma
      patients. Injuries can vary from simple minor penetrating skin wounds to major
      life-threatening soft and hard tissue damage with concurrent complex metabolic
      ramifications. This article reviews the diagnostic and therapeutic options for
      each type of injury.

PMID- 16787792
TI  - Management of specific skin wounds.
AB  - This article deals with the range of skin conditions found in the dog and the
      cat, including intertriginous diseases, dermal sinuses, chronic lesions involving
      the limbs, and specific wound infections for which surgical intervention may play
      a useful role in their successful management.

PMID- 16787793
TI  - Tail and perineal wounds.
AB  - Tail and perineal wounds arise from various causes. Reconstructive techniques are
      beneficial to the resolution of congenital, traumatic, and neoplastic conditions
      that involve the tail and perineum. This article reviews some common and not so
      common conditions and the techniques to treat them effectively.

PMID- 16787794
TI  - The association of preprocedural anxiety and the success of procedural sedation
      in children.
AB  - PURPOSE: To investigate the association between a child's preprocedural state
      anxiety and the success of sedation. METHODS: A consecutive sample of children
      aged 2 through 17 years requiring sedation for a procedure was enrolled. Pain,
      preprocedural anxiety (range, 0-9), and success of sedation (10=most successful)
      were measured. RESULTS: Fifty-nine patients were enrolled. The median age was 7
      years. The median anxiety score was 1.0 (interquartile ratio, 0-3). Pain and
      anxiety were weakly correlated (r=.21, P>.10). The mean sedation score was 7.8
      (+/-2.2). Preprocedural anxiety and successful sedation were inversely correlated
      (r=-0.31, P=.002). Sedation was successful in 81% of children with anxiety scores
      below the median and 52% with anxiety scores above the median (P=.02). Children
      with low anxiety were 3.8 times more likely to be successfully sedated (95%
      confidence interval, 1.19-12.14). CONCLUSION: Our data suggest that preprocedural
      state anxiety is associated with the success of sedation in children.

PMID- 16787795
TI  - A new algorithm for the initial evaluation and management of supraventricular
      tachycardia.
AB  - Interpretations by physicians and those generated by electrocardiograph computer
      softwares have poor ability to recognize different types of supraventricular
      tachycardia (SVT). Therefore, we developed and tested a new SVT algorithm based
      on easily identifiable morphological characteristics and a simple dichotomous
      yes/no format regarding initial electrocardiographic manifestation and response
      pattern. The algorithm was then tested by medical house staff during the initial
      evaluation of 50 adult ED and cardiac intensive care unit patients suspected of
      having SVT. For a wide representation of SVTs, the new algorithm gave an overall
      diagnostic accuracy rate of 90%. Adenosine use was limited to 54% of the cases.
      No patient developed hemodynamic instability after algorithm-dictated
      interventions were carried out. Electrocardiograph computer-generated diagnoses
      correctly identified the specific type of SVT in 38% of the cases. This study
      shows the effectiveness of the proposed new algorithm in the rapid bedside
      evaluation and management of SVTs and confirms that computer-generated diagnoses
      are unreliable.

PMID- 16787796
TI  - Ibutilide to expedite ED therapy for recent-onset atrial fibrillation flutter.
AB  - OBJECTIVE: Ibutilide is a type III antiarrhythmic agent approved for the
      pharmacologic conversion of atrial fibrillation (AF) and atrial flutter (AFl).
      Previous studies conducted outside the ED setting have demonstrated conversion
      rates of 60% to 80%. This response has been highest in patients with recent-onset
      AF-AFl. These observations and the 4-hour half-life of ibutilide suggest that it
      may be an excellent drug with which to treat AF-AFl in the ED. The purpose of the
      study was to examine the efficacy and safety of ibutilide in terminating AF-AFl
      in patients who present to the ED with symptoms of less than 3 days' duration,
      neither angina nor heart failure, and no comorbid conditions that require
      admission. METHODS: Among 36 enrolled patients, the admission electrocardiogram
      demonstrated AF in 26 and AFl in 10. Ibutilide 1 mg was administered
      intravenously for 10 minutes. If sinus rhythm was not present 10 minutes after
      the infusion concluded, a second infusion of 1 mg was given. Successful
      conversion was defined as restoration of sinus rhythm within 1 hour after the
      last dose of ibutilide. RESULTS: Sixteen (61.5%) of 26 patients with AF and 9
      (90%) of 10 patients with AFl converted to sinus rhythm (overall conversion
      rate=69%). The mean time to arrhythmia termination was 19+/-9 minutes. The mean
      stay in the ED was 16.2 hours. No significant complications occurred. CONCLUSION:
      We conclude that ibutilide is an excellent therapy option for restoring sinus
      rhythm in the ED. Its use may obviate the need for admission, avoid the risks and
      inconveniences of general anesthesia to perform electrical cardioversion, and
      reduce the ED length of stay in selected patients with recent-onset atrial
      arrhythmias.

PMID- 16787797
TI  - Older patients presenting to a county hospital ED after a fall: missed
      opportunities for prevention.
AB  - Little is known about the characteristics of elderly persons who present to an ED
      after a fall or about the nature of the care received for the fall itself. We
      identified elders presenting to a large urban United States ED after a fall,
      determined risk factors that may have contributed to the fall, and assessed the
      extent to which falls were addressed in the ED setting. One hundred seventeen
      fallers were identified. Nearly half were aged 80 years or older. After age,
      polypharmacy was the most common fall risk factor, followed by more than 1
      contributing medical condition and cognitive impairment. Fall risk factors
      differed significantly for older compared with younger subgroups. More than half
      (57%) who had fallen were admitted. Of the remainder who fell and were
      discharged, more than half were scheduled for follow-up of their fall-related
      injury only, with no follow-up scheduled to address prevention of future falls.
      In summary, elders who present to an ED after having fallen have a variety of
      risk factors for falls that can be addressed to reduce their risk of future falls
      and injury; however, many may not receive such follow-up care. There must be
      increased awareness among ED providers of the need for a medical evaluation of a
      fall. Randomized trials evaluating the effect of a focused fall risk factor
      assessment after presentation to the ED may be warranted.

PMID- 16787798
TI  - Potential benefit of transesophageal defibrillation: an experimental evaluation.
AB  - INTRODUCTION: Because of the proximity of the esophagus to the heart,
      transesophageal defibrillation might increase defibrillation success. We assessed
      the defibrillation threshold (DFT) of transesophageal defibrillation compared
      with standard transthoracic defibrillation. METHODS: Defibrillation success and
      DFTs were determined in 22 female pigs with high (68+/-4 kg, n=12) or low body
      weight (39+/-1 kg, n=10). After induction of ventricular fibrillation, biphasic
      shocks were delivered between two cutaneous patch electrodes (sternal and apical
      position) or between an esophageal and two cutaneous patch electrodes in a
      sternal and apical position. The esophageal electrode was integrated into a latex
      sheath covering a standard transesophageal echocardiography probe. RESULTS: In 5
      of 12 pigs with high body weight, external defibrillation failed despite 3
      consecutive 200-J shocks, whereas subsequent transesophageal defibrillation was
      successful with the first shock. In the remaining 7 pigs, a more than 50%
      reduction in DFT was obtained with transesophageal defibrillation compared with
      standard biphasic external defibrillation (67+/-27 vs 164+/-23 J, P<.001). Pigs
      with lower body weight were successfully defibrillated by both transthoracic and
      transesophageal shocks. The DFT in pigs with low body weight was significantly
      lower using transesophageal defibrillation compared with transthoracic shocks
      (65+/-15 vs 99+/-38 J, P<.05). CONCLUSIONS: In this animal model, nonresponders
      to standard external defibrillation could successfully be defibrillated via an
      esophageal-cutaneous electrode configuration. Overall, an almost 50% DFT
      reduction was achieved by transesophageal defibrillation. Transesophageal
      defibrillation may provide an additional tool for terminating VF, which is
      refractory to external defibrillation, eg, in patients with very high body
      weight.

PMID- 16787799
TI  - Boehler's angle and the critical angle of Gissane are of limited use in
      diagnosing calcaneus fractures in the ED.
AB  - STUDY OBJECTIVES: The aim of this study was to determine the use of Boehler's
      angle (BA) and the critical angle of Gissane (CAG) in diagnosing calcaneus
      fractures in the ED. DESIGN: The study was conducted as a randomized, blinded,
      case-control trial. CASES: One hundred thirty-three patients older than 15 years
      were included in the study. Sixty-five patients with computed tomography-verified
      calcaneus fractures (gold standard) and 68 ED patients with lateral foot or ankle
      x-rays without calcaneus fractures were included in the study. METHODS: One
      second-year emergency medicine resident, 1 third-year emergency medicine
      resident, 2 board-certified emergency medicine attending physicians, and 1 board
      certified radiologist prospectively reviewed all films using the Picture Archival
      and Communication System digital radiology system. Cases and controls were
      randomized and the participants were blinded to final radiographic diagnoses.
      Participants determined whether there was a fracture on each x-ray and measured
      BA and the CAG using the digital angle tool in the Picture Archival and
      Communication System. RESULTS: Emergency physicians were 97.9% accurate in
      diagnosing calcaneus fractures (range, 97% to 99%). The mean kappa value for
      emergency physicians was 0.96 (range, 0.94-0.985). Receiver operating
      characteristic curves were constructed for BA and the CAG. When compared with the
      gold standard, the area under the curve for BA ranged from 0.82 to 0.88. The area
      under the curve for the CAG ranged from 0.45 to 0.67. BA had an interclass
      correlation coefficient of 0.84 (95% confidence interval, 0.79-0.87). The CAG
      interclass correlation was 0.52 (95% confidence interval, 0.43-0.60). One
      fracture was missed by the radiologist and all of the emergency physicians
      because it was only visible on computed tomography. CONCLUSION: BA is somewhat
      helpful and the CAG is not useful in diagnosing calcaneus fractures in the ED.
      Interrater reliability for BA is excellent, but for the CAG, it is poor.
      Emergency physicians were 97.9% accurate in making the diagnosis by reviewing the
      plain films without "assistance" of the angle measurements.

PMID- 16787800
TI  - ED visits by older adults for ambulatory care-sensitive and supply-sensitive
      conditions.
AB  - OBJECTIVES: The aim of this study was to examine the effect of advanced age on ED
      outcomes, including hospitalization for any reason, ambulatory care-sensitive
      hospitalizations (ACSHs), and supply-sensitive hospitalizations. METHODS: A
      secondary data analysis of the National Hospital Ambulatory Care Survey was
      conducted. National estimates of patient visits were obtained using available
      sampling weights from National Hospital Ambulatory Care Survey, and population
      estimates were calculated using estimates published by the US Census Bureau.
      RESULTS: Older adults made 48 million patient visits to ED between 2000 and 2002.
      Overall, 20.3% was for an ambulatory care-sensitive condition, yielding 5 million
      ACSH, whereas 62% was for a supply-sensitive condition, yielding 9.5 million
      supply-sensitive hospitalizations. Residents from nursing homes and patients aged
      85 years or older were more likely to be hospitalized for any reason, for ACSH,
      and for supply-sensitive conditions. CONCLUSIONS: Further research is needed to
      understand how comorbidity contributes to increasing ED and hospital use among
      older adults.

PMID- 16787801
TI  - Beta-blocker use in elderly ED patients with acute myocardial infarction.
AB  - BACKGROUND: Despite the effectiveness of early beta-blocker (BB) use in reducing
      mortality in acute myocardial infarction (AMI), they remain underutilized in the
      emergency department (ED) management of AMI. The elderly, with higher AMI
      mortality, and women, may be particularly vulnerable to underutilization of BB.
      OBJECTIVE: To determine the effect of age and gender on BB use in AMI in the ED.
      METHODS: A retrospective study of all ST-elevation AMI (STEMI) ED patients
      presenting to a community hospital ED from 2001 to 2003. Any contraindication to
      BB use (hypotension, bradycardia, AV block, active bronchospasm, and active
      congestive heart failure) was determined. Chi-square analysis was used to
      determine differences by gender and age. RESULTS: Three hundred eighty-five
      patients with STEMI were identified. Thirty-eight percent were women and 71% were
      over 60 years of age. Of the 270 (70%) who did not receive BB, 141 (52%) had
      contraindications to BB use. The total BB eligible group was 244 (63%). Of
      patients without contraindications to BB, 53% did not receive BB in the ED. By
      gender, 83 (54%) males and 46 (51%) females did not receive BB (P=.669). By age,
      96 subjects (59%) over age 60 and 33 subjects (41%) under age 60 did not receive
      BB (P=.011). CONCLUSION: Despite convincing evidence of effectiveness, BB remain
      underutilized in ED management of AMI, especially in the elderly. There does not
      appear to be a gender difference in BB use. Education programs should be directed
      towards emergency physicians regarding BB use in AMI, especially in elderly ED
      patients.

PMID- 16787802
TI  - Influence of activated charcoal on the pharmacokinetics and the clinical features
      of carbamazepine poisoning.
AB  - Carbamazepine (CBZ) poisoning has been associated with cases of severe toxicity
      and death. Multiple-dose activated charcoal was proposed to enhance the clearance
      of CBZ elimination, but there are no prospective controlled studies that
      demonstrated a change in clinical outcome after the use of multiple-dose
      activated charcoal. The aim of this study was to determine the CBZ elimination
      kinetics and the evolution of clinical features according to the dose of
      activated charcoal in acute poisoning patients. It is a prospective study for 6
      months, from January to June 2004, including all pure acute CBZ-poisoned
      patients. Twelve patients were randomized to receive a multiple-dose activated
      charcoal (G1) or a simple dose of 1 g/kg (G2). Their mean age was 27.6+/-12.2
      years; the Simplified Acute Physiology Score (SAPS II), 16.37+/-8.46; and the
      Acute Physiology and Chronic Health Evaluation (APACHE II), 8+/-3.96. They were 8
      men and 4 women. The mean concentration of blood CBZ at hospital admission was of
      29.42+/-6.68 mg/L. Each group includes 6 patients. The peak value of blood CBZ
      was comparable in the 2 groups: 33+/-3.46 mg/L (G1) vs 32.6+/-5.63 (G2) (P=.5);
      the requirement of mechanical ventilation was similar also (3 in each group). The
      duration of both coma and mechanical ventilation was significantly decreased in
      the first group compared with the second: 20.33+/-3.05 vs 29.33+/-4.11 hours for
      coma (P=.02) and 24.1+/-4.2 vs 36.4+/-3.6 hours for mechanical ventilation
      (P=.001). The length of stay was also significantly decreased in the first group:
      30.3+/-3.4 vs 39.7+/-7.3 hours in the second group (P=.000006). Concurrently, we
      have noted a significant constant reduction of the half-life of CBZ from serum in
      the first group: 12.56+/-3.5 hours after multiple dose vs 27.88+/-7.36 hours
      after a simple dose (P=.0004). This decrease was correlated to the dose of
      charcoal. In summary, we can conclude that multiple-dose activated charcoal is
      more efficient than simple-dose; it permits a constant decrease of the half-life
      of blood CBZ without any rebound effect and could improve the prognosis by
      reducing the duration of coma and the length of stay.

PMID- 16787804
TI  - The relative lymphocyte count on hospital admission is a risk factor for long
      term mortality in patients with acute heart failure.

PMID- 16787803
TI  - Intimate partner violence and mental health symptoms in African American female
      ED patients.
AB  - BACKGROUND: Intimate partner violence (IPV) victims often seek care in the ED,
      whether for an injury from abuse or other sequelae such as mental health
      symptoms. OBJECTIVES: The objective of the study was to assess whether depressive
      symptoms, posttraumatic stress disorder (PTSD), and suicidality were associated
      with physical, sexual, or emotional IPV in African American female ED patients
      and to determine if experiencing multiple types of abuse was associated with
      increased mental health symptoms. METHODS: All eligible African American female
      patients were approached in the ED waiting room during study periods. Patients
      participated in the screening process via a computer kiosk. Questions regarding
      IPV and mental health symptoms were asked using validated tools. RESULTS: In this
      prospective cohort, 569 participated and 36% of those in a relationship in the
      past year (n=461) disclosed that there were victims of IPV in the past year. In
      the past year, 22% experienced recent physical abuse, 9% recent sexual abuse, and
      32% recent emotional abuse. A Pearson correlation was conducted and showed that
      all mental health symptoms were positively correlated with each type of IPV and
      each type of mental health symptom category. Mental health symptoms increased
      significantly with amount of abuse: depression (odds ratio [OR], 5.9 for 3 types
      of abuse), PTSD (OR, 9.4 for 3), and suicidality (OR, 17.5 for 3). CONCLUSIONS:
      Emotional, sexual, and physical IPV were significantly associated with mental
      health symptoms. Each type of abuse was independently associated with depression,
      suicidality, and PTSD. Experiencing more than 1 type of abuse was also correlated
      with increased mental health symptoms.

PMID- 16787805
TI  - Percutaneous transtracheal emergency ventilation during respiratory arrest:
      comparison of the oxygen flow modulator with a hand-triggered emergency jet
      injector in an animal model.
AB  - The oxygen flow modulator is a device for percutaneous transtracheal emergency
      ventilation. Simulating a respiratory arrest situation, we studied the effects of
      this device in comparison with a hand-triggered emergency jet injector during
      pulmonary resuscitation. Nine pigs were anesthetized and mechanically ventilated.
      After surgical exposure, an emergency transtracheal airway catheter was inserted
      into the trachea. Ventilation was stopped until SpO2 was below 70%. Each animal
      was subsequently randomly ventilated via the transtracheal airway catheter with
      either the hand-triggered emergency jet injector or the oxygen flow modulator.
      After 10 minutes, respiratory and hemodynamic parameters were recorded.
      Ventilation was stopped again until SpO2 reached 70%, and the animal was
      ventilated with the second device. With both devices, pulmonary resuscitation was
      successful. Whereas PaO2 differed not significantly between the two devices,
      PaCO2 was lower during percutaneous transtracheal ventilation with the hand
      triggered emergency jet injector.

PMID- 16787806
TI  - Acute thrombotic disorders.
AB  - The acquired hypercoagulable states are responsible for a broad range of
      thrombotic and thromboembolic disorders. Symptoms and signs of acute ischemia or
      organ dysfunction will lead many of these patients to seek care in EDs. Proper
      diagnosis and therapy must be based on an understanding of epidemiology and
      pathophysiology. Immediate anticoagulation with heparin may not always be the
      treatment of choice; careful analysis of clinical and laboratory parameters is
      necessary to arrive at the safest and most effective course of action. Newer
      anticoagulants, including low-molecular-weight heparins and nonheparin compounds,
      are changing the therapeutic approach to many of these disorders.

PMID- 16787808
TI  - Sudden onset of paraplegia from acute aortic occlusion: a review of 2 cases and
      their unique presentation.
AB  - Acute aortic occlusion is an uncommon entity requiring prompt recognition and
      intervention to limit morbidity and mortality. We describe 2 patients with acute
      aortic occlusion who presented uniquely with sudden onset of paraplegia. In
      addition, we highlight their circuitous diagnostic course and the adverse impact
      of diagnostic delay in their management and outcome.

PMID- 16787810
TI  - Do Rh-negative women with first trimester spontaneous abortions need Rh immune
      globulin?
AB  - OBJECTIVE: To examine whether literature supports the use of Rh immune globulin
      in Rh-negative women with first trimester spontaneous abortions to prevent
      maternal sensitization to the fetal Rh antigen and subsequent fetal morbidity and
      mortality. METHODS: We searched MEDLINE (1966-2005), the Cochrane Central
      Register of Controlled Trials, EMBASE (1990 to 2005), and the reference sections
      of the articles found. The search is considered updated to December of 2005.
      Search terms included vaginal bleeding, Rh negative, Rh immune globulin, RhoGAM,
      isoimmunization, sensitization, first trimester pregnancy, threatened, and
      spontaneous abortion. RESULTS: The evidence to support the use of Rh immune
      globulin for a diagnosis of first trimester spontaneous abortion is minimal.
      There is a paucity of well-designed research that examines maternal sensitization
      or hemolytic disease of the newborn as an outcome in patients receiving, versus
      not receiving, Rh immune globulin in first trimester bleeding. There is
      significant evidence to demonstrate fetomaternal hemorrhage in first trimester
      spontaneous abortions; yet, no studies demonstrate subsequent maternal
      sensitization or development hemolytic disease in the fetus as a result of this
      hemorrhage. CONCLUSION: In summary, there is minimal evidence that administering
      Rh immune globulin for first trimester vaginal bleeding prevents maternal
      sensitization or development of hemolytic disease of the newborn. The practice of
      administering Rh immune globulin to Rh-negative women with a first trimester
      spontaneous abortion is based on expert opinion and extrapolation from experience
      with fetomaternal hemorrhage in late pregnancy. Its use for first trimester
      bleeding is not evidence-based.

PMID- 16787807
TI  - Prescribing to older ED patients.
AB  - The purpose of this article is to assist emergency physicians in selecting safe
      and effective drug therapy for seniors. Because safer alternatives exist,
      medications on the Beers list of potentially inappropriate medications should
      generally be avoided. We also review risks associated with several classes of
      medications: nonsteroidal anti-inflammatory drugs, benzodiazepines, and
      anticholinergic medications. They are associated with adverse outcomes when taken
      by older adults and should be used with caution. We also address the use of
      opioid medications in seniors. Although they are not without risk, opioids are
      generally safe with slow titration, precautions, and a bowel regimen to prevent
      constipation. Prescribers should also consider the need for estimating creatinine
      clearance when prescribing medications that require dosage adjustment in the
      setting of renal insufficiency. Two areas in need of research are identifying the
      proper dosing and safety of medications in seniors and prescribing with
      electronic decision support to assist in prescribing decisions.

PMID- 16787809
TI  - Blunt chest trauma: utility of radiological evaluation and effect on treatment
      patterns.
AB  - Minor chest wall trauma is a common complaint in the emergency department (ED)
      (Barnea Y, Kashtan H, Skornick Y, Werbin N. Isolated rib fractures in elderly
      patients: mortality and morbidity. Can J of Surgery 2002;45(1):43-6; Lee RB, Bass
      SM, Morris JA, Mackenzie EJ. Three or more rib fractures as an indicator for
      transfer to a level I trauma center. J Trauma 1990;30:689-94; Dubinsky I, Low A.
      Non-life-threatening blunt chest trauma: Appropriate investigation and treatment.
      Am J Emerg Med 1997;15(3):240-3). Up to 50% of rib fractures may be missed on
      standard x-ray (Ziegler DW, Agarwal NN. The morbidity and mortality of rib
      fractures. J Trauma 1994;37:975-9; Palvanen M, Kannus P, Niemi S, Parkkari J.
      Hospital-treated minimal-trauma rib fractures in elderly Finns: long-term trends
      and projections for the future. Osteoperosis International). Little consensus
      exists among emergency physicians with respect to the workup of minor blunt chest
      trauma. The purpose of this study was to evaluate the accuracy of emergency
      physicians in interpreting rib radiographs and to determine if that
      interpretation resulted in any variance in treatment patterns. Our study is a
      retrospective study of 271 charts from a community-based teaching hospital from
      August 2000 to August 2002. Patients were excluded if they suffered major trauma.
      The treatment rendered was categorized. Categories included over-the-counter
      medication, nonsteroidal anti-inflammatory drugs, narcotics, and muscle
      relaxants. The overall chi2 calculation showed no differences between the
      fractured group and the no fracture group (P=.072). From this, it can be
      concluded that there were no between-group differences in drugs prescribed based
      on whether a fracture was diagnosed by the ED physician. Indicating that the
      interpretation of the rib series does not influence the physicians treatment
      plan.

PMID- 16787811
TI  - Design rationale and intended use of a short optical stylet for routine
      fiberoptic augmentation of emergency laryngoscopy.
AB  - Patient safety in emergency airway management has traditionally relied upon
      prediction of difficult laryngoscopy and alternative intubation devices.
      Unfortunately, screening tests for difficult laryngoscopy have poor predictive
      value, and alternative devices are often not suitable for emergency airways. RSI
      performed with hit or miss repetitive laryngoscopy followed by delayed deployment
      of rarely used rescue devices is inherently hazardous. First pass success with
      laryngoscopy should be a benchmark of quality and patient safety in emergency
      airway management. By making a commitment to minimally modify practice and expand
      our skill set, fiberoptic augmentation of every laryngoscopy can promote patient
      safety through the avoidance of repetitive laryngoscopy and esophageal
      intubation. This article presents the design rationale and intended use of a new
      short optical stylet for the routine augmentation of emergency direct
      laryngoscopy.

PMID- 16787812
TI  - Diagnosis of ovarian torsion in a hemodynamically unstable pediatric patient by
      bedside ultrasound in the ED.

PMID- 16787813
TI  - Case reports of death after nonionic iodine contrast medium injection during
      spiral computed tomography scan performed for suspected pulmonary embolism.

PMID- 16787815
TI  - Should blind internal jugular venous catheterization be avoided in a patient with
      ipsilateral permanent pacemaker implant?

PMID- 16787814
TI  - Severe destructive sinusitis and orbital apex syndrome as a complication of
      intranasal cocaine abuse.

PMID- 16787816
TI  - Thrombolytic therapy for massive pulmonary embolism 12 hours after cesarean
      delivery despite contraindication?

PMID- 16787817
TI  - Parenteral glyphosate-surfactant herbicide intoxication.

PMID- 16787818
TI  - Arthroscopic retrieval of sewing needle fragments from the knees of 3 children.
AB  - Penetrating knee joint injuries are less common in children than adults. Foreign
      bodies that penetrate into the knee joint often mimic septic arthritis and
      synovitis. In the management of such cases, rheumatological tests, medical
      imaging, and finally arthroscopy are essential. We present 3 children who
      presented to our ED with broken sewing needles (home-use variety) in their knee
      joints. By history, these incidents occurred while playing indoors. Clinical
      findings were similar to those of acute septic arthritis. Patients were treated
      successfully by arthroscopic surgery and were symptom-free at follow-up several
      months later.

PMID- 16787819
TI  - Where does troponin I derive from in rhabdomyolysis?

PMID- 16787821
TI  - Agitation complicating procedural sedation with etomidate.

PMID- 16787822
TI  - An unusual cause of iatrogenic bladder rupture.

PMID- 16787823
TI  - Does aging influence quality of care for acute myocardial infarction in the
      prehospital setting? Elderly patients with acute myocardial infarction.

PMID- 16787824
TI  - Establishing a pharmacy presence in the ED.

PMID- 16787825
TI  - Caution with naloxone use in asthmatic patients.

PMID- 16787826
TI  - Potential impact of pandemic influenza on blood safety and availability.
AB  - The spread of H5N1, an avian influenza A virus, to many countries and the direct
      infection of humans by this virus have increased awareness of the likelihood of a
      pandemic among humans. The potential impact of pandemic influenza on the safety
      of the blood supply should be small because of the limited viremia and the nature
      of respiratory tract infection of influenza viruses. However, the potential
      impact of pandemic influenza on the availability of the blood supply could be
      significant because of reduced donation from blood donors and reduced staff
      capacity at blood centers during a pandemic. On the other hand, there could be
      reduced hospital admissions and reduced transfusions, at least for certain blood
      products, which should result in reduced demand for blood products. Studies are
      needed to further assess the likely impact of a pandemic on the blood supply and
      also of the possible intervention options.

PMID- 16787827
TI  - An overview of prion biology and the role of blood filtration in reducing the
      risk of transfusion-transmitted variant Creutzfeldt-Jakob disease.
AB  - Prions are infectious proteins believed to be responsible for a variety of
      progressive and fatal neurodegenerative diseases, collectively referred to as
      transmissible spongiform encephalopathies (TSE). By 1996, it was recognized that
      ingestion of beef from cattle afflicted with a TSE known as bovine spongiform
      encephalopathy, could result in a devastating human TSE known as variant
      Creutzfeldt-Jakob disease (vCJD). Two recent reports of probable transfusion
      transmitted vCJD have raised concerns about the safety of the blood supply. The
      relatively long asymptomatic latency of vCJD, as well as the lack of sensitive
      and specific antemortem tests, increase the risk that asymptomatic, infected
      individuals may become blood donors. To this point, donor deferral has been a
      strategy used to reduce this risk. Nevertheless, this strategy may be unreliable
      and, furthermore, may threaten blood availability. Leukoreduction has also been
      helpful in reducing cell-associated infectious prion, which has been reported to
      reduce up to 42% of the infectivity in blood. Proprietary prion affinity surface
      modifications have been developed and applied to filters, which exploit an
      understanding of the unique chemical characteristics of prion surfaces. These
      have been successfully adapted to existing high-efficiency blood filter matrices
      for the reduction of prions present in blood components for transfusion.

PMID- 16787828
TI  - The cis-AB blood group phenotype: fundamental lessons in glycobiology.
AB  - The cis-AB phenotype can raise questions about an apparently paradoxical
      inheritance of the ABO blood group, such as the birth of an O child from an AB
      mother. These subtype ABO alleles confer the ability to create both A and B
      antigens with a single enzyme. A variety of different cis-AB enzymes have been
      reported and many feature an interchange of amino acids between the normal A
      enzyme sequence and its B counterpart, rendering the mutant enzyme capable of
      creating both antigens. The resulting red blood cells do not usually express A or
      B antigen at the same level that would be expected on common group A(1) or B red
      blood cells, and the results of investigations into the kinetics of the cis-AB
      enzyme more clearly predict the extent of antigen expression. By correctly
      identifying the cis-AB phenotype, the blood bank can be of assistance to a
      clinician faced with a patient with what appears to be a genetically impossible
      ABO blood group.

PMID- 16787829
TI  - Home is where the heart is: do blood transfusions belong there too?
AB  - Blood transfusions performed outside of the hospital (OOH), particularly those in
      the patient's home, require special attention to reduce the added risk of being
      at an increased distance from emergency medical care. The situation must be
      carefully evaluated to be sure that the added risk is minimal and is balanced by
      substantial benefit to the patient. Consideration should be given in advance as
      to which patients will be eligible for OOH transfusions and what criteria must be
      met for the location of the transfusion. When blood transfusions are performed in
      the home, a second adult should be available to be able to assist the
      transfusionist and to monitor the patient after the transfusionist leaves. A
      facility engaged in OOH transfusions must adhere to all regulations and should
      establish quality assurance measures concerning this OOH transfusion practice. An
      OOH blood transfusion program must address these and other issues before the
      first patient is enrolled.

PMID- 16787831
TI  - Basile J. Luyet and the beginnings of transfusion cryobiology.
AB  - The first president of the Society for Cryobiology was a Roman Catholic priest
      born in a mountain village in Switzerland. Basile J. Luyet immigrated to the
      United States in 1929 with doctorates in biology and in physics and then devoted
      his life to studies described best by the title of his early monograph "Life and
      Death at Low Temperatures." Established in the faculty at St. Louis University,
      he pursued studies on living matter in the cold that in midcareer led to efforts
      to vitrify red cells by ultrarapid cooling. As a purist who wanted to vitrify
      living matter without the assistance of cryoprotectant additives, he did not
      succeed with red cells. However, his 40 years of exploration of the biology of
      the cold joined physical chemistry with biology and made cryobiology into a new
      branch of scientific thought. A very formal man, he served both his God and his
      science with the dictum that "truth does not contradict truth." His contributions
      are preserved in the knowledge and wisdom that he created and in the memory of
      the people of the Alpine village of his birth.

PMID- 16787830
TI  - Effects of cardiac surgery on hemostasis.
AB  - Cardiac surgery affects both coagulation and platelet function. Revision of
      surgery due to bleeding has to be performed in 2% to 6% of patients undergoing
      cardiac surgery and is generally associated with a marked deterioration in
      prognosis. Factors contributing to acquired hemostatic abnormalities in cardiac
      surgery include the use of anticoagulants as well as the activation and
      consumption of coagulation factors and platelets induced by the extracorporeal
      circulation. Prophylactic use of antifibrinolytic agents such as aprotinin and
      tranexamic acid has been demonstrated to reduce the blood loss by half. Adequacy
      of heparin-induced anticoagulation in the perioperative setting is commonly
      controlled by the activated clotting time. This method also indicates the correct
      reversal of the heparin effect by protamine. In recent years, thrombelastography
      has proved to be valuable for diagnosis of coagulopathy associated with cardiac
      surgery. In addition, the use of thrombelastography-based algorithms has been
      shown to reduce transfusion requirements. In contrast to point of care methods,
      laboratory assessment of hemostasis is more time-consuming and, thus, often not
      as rapidly available as required. At this time, the therapy for perioperative
      hemostatic abnormalities is based mainly on the administration of blood
      components (fresh frozen plasma and platelet concentrates). In the future,
      recombinant activated factor VIIa might prove to be a therapeutic option in
      patients with otherwise untractable bleeding, but the efficacy of recombinant
      activated factor VIIa has yet to be defined for this indication.

PMID- 16787832
TI  - Comment: transfusion in war and peace.

PMID- 16787834
TI  - Neuroprotective and symptomatological action of memantine relevant for
      Alzheimer's disease--a unified glutamatergic hypothesis on the mechanism of
      action.
AB  - The involvement of glutamate mediated neurotoxicity in the pathogenesis of
      Alzheimer's disease is finding increasingly more acceptance in the scientific
      community. Central to this hypothesis is the assumption that in particular
      glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in
      a tonic rather than a phasic manner. Such continuous mild activation leads under
      chronic conditions to neuronal damage. Moreover, one should consider that
      impairment of plasticity (learning) may result not only from neuronal damage per
      se but also from continuous activation of NMDA receptors. To investigate this
      possibility we tested whether overactivation of NMDA receptors using either non
      toxic doses/concentrations of a direct NMDA agonist or through an indirect
      approach--decrease in magnesium concentration--produces deficits in plasticity.
      In fact NMDA both in vivo (passive avoidance test) and in vitro (LTP in CA1
      region) impaired learning and synaptic plasticity. Under these conditions
      memantine which is an uncompetitive NMDA receptor antagonist with features of
      "improved magnesium" (voltage dependence, affinity) attenuated the deficit. The
      more direct proof that memantine can act as a surrogate for magnesium was
      obtained in LTP experiments under low magnesium conditions. In this case as well,
      impaired LTP was restored in the presence of therapeutically relevant
      concentrations of memantine (1 microM). In vivo, doses leading to similar
      brain/serum levels produce neuroprotection in animal models relevant for
      neurodegeneration in Alzheimer's disease such as neurotoxicity produced by
      inflammation in the NBM or beta-amyloid injection to the hippocampus. Hence, we
      postulate that if in Alzheimer's disease overactivation of NMDA receptors occurs
      indeed, memantine would be expected to improve both symptoms (cognition) and slow
      down disease progression because it takes over the physiological function of
      magnesium.

PMID- 16787833
TI  - Neuroprotective and neurorestorative strategies for neuronal injury.
AB  - Mechanisms of neuronal cell death in apoptosis and necrosis are examined.
      Neurotoxic processes underlying cellular destruction may involve N-methyl-D
      aspartate (NMDA) receptor activation and/or activation of neuronal nitric oxide
      synthase but the depletion of energy and generation of free radicals appears to
      be critical. In Alzheimer's disease the damaging effects of peroxynitrite and
      exposure to beta-amyloid peptide is evident. Mitochondrial dysfunction is
      involved in several neurodegenerative diseases including Parkinson's disease,
      amyotrophic lateral sclerosis, Huntington's disease as well as Alzheimer's
      disease and in these disorders the innovations offered by techniques ranging from
      transgenic mouse models of the disorder to cell culture preparations are
      remarkable. Agents of neuroprotection and neurorestoration possess either
      characteristics specific to particular disorders or have a general applicability
      or both. The vast array of agents available are for the most part the objectives
      of laboratory examinations but an increasing selection of compounds are reaching
      the clinical necessities thereby influencing current strategic notions to modify
      tactical contingencies. Among the agents listed are included: inhibitors of the
      enzyme poly-ADP-ribose polymerase, inhibition of apoptotic cell death, agents
      acting on mitochondrial permeability transition, excitatory amino acid
      antagonists, applications of neurotrophins, immunophilins, agents influencing
      heme oxygenase-1 expression and iron sequestration in aging astroglia,
      improvements in mitochondrial energy production or buffering, and finally
      dopaminemimetics with differential affinities for dopamine receptors.

PMID- 16787835
TI  - Strategies for the protection of dopaminergic neurons against neurotoxicity.
AB  - Degenerative diseases of the central nervous system (CNS) frequently have a
      predilection for specific cell populations. An explanation for the selective
      vulnerability of particular neuronal populations and the mechanisms of cell death
      remains, as yet, elusive. Partial elucidation of the processes underlying the
      selective action of neurotoxic substances such as iron, 6-hydroxydopamine (6
      OHDA), glutamate, kainic acid, quinolinic acid or 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), has revealed possible molecular mechanisms for
      neurodegeneration. Hypotheses regarding the neurotoxic mechanisms of these
      substances have evolved based on our understanding of the pathogenesis of cell
      death in neurodegenerative disorders and have been the rationale for
      neuroprotective approaches. Various experimental models have demonstrated that
      monoamine oxidase type B (MAO-B) inhibitors and dopamine agonists exert a
      neuroprotective effect at the cellular, neurochemical and functional levels,
      however as yet it has not been possible to demonstrate an unequivocal
      neuroprotective effect of these substances in clinical studies. This does not
      suggest, however, that the pathogenetic processes underlying neurodegenerative
      disorders are not amenable to neuroprotective treatment. This chapter briefly
      reviews the mechanisms underlying dopaminergic cell death in Parkinson's disease
      (PD) as an example of a neurodegenerative disorder and discusses preclinical
      approaches which attempt to demonstrate the neuroprotective effects of
      representative drugs in experimental models of this disorder. The problems
      associated with carrying out clinical neuroprotective studies aimed to
      demonstrate neuroprotection in PD are also discussed.

PMID- 16787837
TI  - Excitotoxicity of quinolinic acid: modulation by endogenous antagonists.
AB  - Quinolinic acid (QUIN), a product of tryptophan metabolism by the kynurenine
      pathway, produces excitotoxicity by activation of NMDA receptors. Focal
      injections of QUIN can deplete the biochemical markers for dopaminergic,
      cholinergic, gabaergic, enkephalinergic and NADPH diaphorase neurons, which
      differ in their sensitivity to its neurotoxic action. This effect of QUIN differs
      from that of other NMDA receptor agonists in terms of its dependency on the
      afferent glutamatergic input and its sensitivity to the receptor antagonists. The
      enzymatic pathway yielding QUIN produces metabolites that inhibit QUIN-induced
      neurotoxicity. The most active of these metabolites, kynurenic acid (KYNA),
      blocks NMDA and non-NMDA receptor activity. Treatment with kynurenine hydroxylase
      and kynureinase inhibitors increases levels of endogenous KYNA in the brain and
      protects against QUIN-induced neurotoxicity. Other neuroprotective strategies
      involve reduction in QUIN synthesis from its immediate precursor, or endogenous
      synthesis of 7-chloro-kynurenic acid, a NMDA antagonist, from its halogenated
      precursor. Several other tryptophan metabolites--quinaldic acid, hydroxyquinaldic
      acid and picolinic acid--also inhibit excitotoxic damage but their presence in
      the brain is uncertain. Picolinic acid is of interest since it inhibits
      excitotoxic but not neuroexcitatory responses. The mechanism of its anti
      excitotoxic action is unclear but might involve zinc chelation. Neurotoxic
      actions of QUIN are modulated by nitric oxide (NO). Treatment with inhibitors of
      NO synthase can augment QUIN toxicity in some models of excitotoxicity suggesting
      a neuroprotective potential of endogenous NO. In recent studies, certain nitroso
      compounds which could be NO donors, have been reported to reduce the NMDA
      receptor-mediated neurotoxicity. The existence of endogenous compounds which
      inhibit excitotoxicity provides a basis for future development of novel and
      effective neuroprotectants.

PMID- 16787838
TI  - Neuroprotection in Alzheimer's disease - new strategies for treatment.
AB  - Alzheimer's disease is the most common dementia disorder characterized by
      multiple pathological changes in the brain leading to a progressive memory loss
      and other cognitive symptoms producing occupational and social disabilities.
      Although a great deal of progress has been made in recent years in further
      understanding the genetic aberrations and patho-physiological processes of
      Alzheimer's disease there is still no cure of the disease. The transmitter
      replacement therapy is so far the most explored therapy. Three cholinesterase
      inhibitors have so far been approved and presently in clinical use in many
      countries. Although the cholinesterase inhibitors generally appear to produce
      symptomatic effects with palliative effect on existing cognitive disturbances
      recent data suggest that they also may have effect on progression of the disease
      including possible neuroprotective effects. Possible interactions between Abeta
      and cholinergic neurotransmission may exist. Treatment of cells with Abeta causes
      decreased cholinergic activity. Pretreatment of PC12 cells with cholinesterase
      inhibitors such as tacrine and donepezil in clinical relevant concentrations can
      attenuate Abeta (25-35) toxicity through mechanisms which may be mediated via
      nicotinic receptors. Estrogen has been shown to protect against Abeta toxicity in
      different cell lines and also to reduce the formation of Abeta. Its mechanism for
      the neuroprotective effect is however not fully clarified. A potentiation of the
      clinical effect of cholinesterase inhibitors in Alzheimer patients has been given
      together with estrogen. Experimental data suggest that the neuroprotective effect
      of estrogen as studied in PC12 cells was mediated at least partly via the
      alpha(7) nicotinic receptor. Treatment with Abeta in nanomolar concentrations for
      7 days in PC12 cells significantly decreased the number of nicotinic receptor
      binding sites and mRNA levels. The effects by Abeta on nicotinic receptors are
      prevented by nicotine pretreatment. The finding suggests a possible link between
      Abeta and nicotinic receptor deficits in Alzheimer patients in the early course
      of the disease.

PMID- 16787836
TI  - Neurotrophic factors in neurodegenerative disorders: model of Parkinson's
      disease.
AB  - Neurotrophic factors are compounds that enhance neuronal survival and
      differentiation. Most of these compounds exert their pharmacological actions on
      selective types of neurons, and therefore, are considered promising new
      therapeutic agents for the treatment of different neurodegenerative disorders
      characterized by selective degeneration of certain neuronal groups. Those
      compounds have been used in humans for several neurological disorders including
      amyotrophic lateral sclerosis--ciliary derived neurotrophic factor (CNTF) and
      brain derived neurotrophic factor (BDNF), Alzheimer's disease and peripheral
      neuropathy--nerve growth factor (NGF) and Parkinson's disease (PD)--glial derived
      neurotrophic factor (GDNF). In spite of well founded clinical experiments by
      previous experimental work in animal models some of these trials have been
      negative. For instance, animal models of PD have shown that several neurotrophic
      factors, including GDNF and other compounds, reduce apoptosis and increase
      resistance of dopamine neurons to neurotoxins in vitro. These compounds prevent
      or recover the damage to dopamine neurons of rodents and primates produced by
      chemical or mechanical acute lesions including 6-OH-DA, MPTP, methamphetamine and
      axotomy. The differences between the promising results obtained in experimental
      models and the lack of clinical results or excessive toxicity found in humans
      could be attributed to the following reasons: (a) Lack of relevance between the
      pathogenesis of the experimental lesion and the corresponding neurodegenerative
      disorder. (b) Poor correlation between results obtained in acute, self-limited,
      selective deficit produced to experimental animals and those available in more
      complex, chronic and progressive disorders involving patients. (c) Inadequate
      delivery of the active product to the target area in the human brain. (d) Poor
      information from acute experiments in animals which does not predict long-term
      effects of chronic infusion in humans. Further experimental work, therefore, is
      needed to transfer these neurotrophic factors to the clinic.

PMID- 16787839
TI  - Oxidative neuropathology and putative chemical entities for Alzheimer's disease:
      neuroprotective effects of salen-manganese catalytic anti-oxidants.
AB  - Considerable evidence exists that the brains of individuals with Alzheimer's
      disease are subject to elevated levels of oxidative stress, particularly in
      regions exhibiting pathological damage. A major contributor to this oxidative
      stress appears to be the inflammatory process. Activation of rodent microglial
      cells by LPS or beta-amyloid peptide results in a marked up-regulation of
      inducible nitric oxide synthase (iNOS) and corresponding nitric oxide (NO)
      production. Elevated levels of iNOS are also observed in the brains of Alzheimer
      patients. The reaction of NO with superoxide leads to the generation of the
      highly reactive and damaging peroxynitrite free radical species. Peroxynitrite
      appears to play a key role in the generation of an oxidative stress in the
      Alzheimer brain as evidenced by widespread nitrotyrosine immunoreactivity. We
      have employed SIN-1 as a peroxynitrite generating system in cell cultures in
      order to characterize the effects of this free radical on neurons. SIN-1
      treatment of primary rat hippocampal neurons in culture results in neurotoxicity
      by a necrosis mechanism according to electron microscopic criteria. One approach
      to limiting peroxynitrite mediated damage is to limit superoxide production. An
      approach we have evaluated is treatment with salen manganese compounds, a class
      of catalytic antioxidant compounds which behave as superoxide dismutase
      (SOD)/catalase mimetics to detoxify superoxide. A number of such salen manganese
      compounds, including EUK-8 and EUK-134, can markedly protect primary rat cortical
      neurons from hydrogen peroxide mediated oxidative stress. Such salen manganese
      compounds can similarly afford marked neuroprotection to an oxidative stress
      imposed by SIN-1, potentially attributable at least in part to their inherent SOD
      activity. The salen manganese SOD/catalase mimetics represent a promising class
      of catalytic antioxidant for attenuating oxidative stress.

PMID- 16787841
TI  - The putative neuroprotective role of dopamine agonists in Parkinson's disease.
AB  - Parkinson's disease is probably caused by a combination of genetic and
      environmental factors, which trigger a cascade of events that lead to the cell
      death of the dopamine-containing neurons of the substantia nigra pars compacta.
      These processes include oxidative stress, mitochondrial dysfunction,
      excitotoxicity with excess of nitric oxide formation, glial and inflammatory
      abnormalities and apoptosis. Dopamine agonists are chemical compounds that act
      directly on the dopamine receptors without any previous enzymatic
      biotransformation. Besides their symptomatic antiparkinsonian effect, these drugs
      may have neuroprotective properties in Parkinson's disease through different
      possible mechanisms: (a) stimulation of dopamine auoreceptors, reducing thereby
      dopamine turnover; (b) direct antioxidant effects; (c) reduction of
      excitotoxicity induced by excessive subthalamic nucleus firing; (d) inhibition of
      mitochondrial permeability; (e) induction of trophic factors. Dopamine agonists
      have already shown neuroprotective effects on dopaminergic cells against a
      variety of neurotoxins in several in vitro and in vivo studies. Clinical studies
      to detect changes in the progression of the underlying neurodegenerative process
      in patients with Parkinson's disease treated with dopamine agonists, by assessing
      the dopamine terminal function in the striatum by means of PET and SPECT
      techniques are under way.

PMID- 16787842
TI  - Death and neuroprotection of retinal ganglion cells after different types of
      injury.
AB  - In adult Sprague-Dawley rats, retinal ganglion cell survival was investigated
      after intraorbital optic nerve section and after transient ischemia of the retina
      induced by elevation of the intraocular pressure or by selective ligature of the
      ophthalmic vessels. The thickness of the inner nuclear and inner plexiform layers
      was also assessed after transient periods (120 min) of retinal ischemia induced
      by selective ligature of the ophthalmic vessels. In addition, we have also
      investigated the neuroprotective effects of different substances in these
      paradigms. The intraocular injection of brain-derived neurotrophic factor
      increased RGC survival after retinal ischemia induced by elevation of the
      intraocular pressure or by selective ligature of the ophthalmic vessels. The
      caspase-inhibitor Z-DEVD increased retinal ganglion cell survival after optic
      nerve section and also after 90 min of retinal ischemia induced by selective
      ligature of the ophthalmic vessels. The peptide Bcl-2 did not increase retinal
      ganglion cell survival after optic nerve section but increased retinal ganglion
      cell survival after 60 or 90 min of retinal ischemia induced by selective
      ligature of the ophthalmic vessels. Finally, BDNF, nifedipine, naloxone and bcl-2
      prevented in part the decrease in thickness of the inner nuclear layer and inner
      plexiform layer induced by selective ligature of the ophthalmic vessels. Our
      results suggest that retinal ganglion cell loss induced by different types of
      injury, may be prevented by substances with neuroprotective effects, by altering
      steps of the cascade of events leading to cell death.

PMID- 16787840
TI  - The neuroprotectant properties of glutamate antagonists and antiglutamatergic
      drugs.
AB  - In the slowly progressive neurodegenerative disorders like Parkinson's disease
      and Alzheimer's disease very different neuronal populations undergo degenerative
      processes, although the cascades of cellular events leading to death are supposed
      to be similar. We suggest that the complex pattern of degeneration in Parkinson's
      disease depends on two processes, a 'primary neurodegeneration' that takes place
      in the striato-nigral dopamine neurons and a 'secondary degeneration', occurring
      in distant structures of the basal ganglia network. For the purpose of explaining
      the regionally different expression of 'primary neurodegeneration' in different
      diseases, we postulate that the origin of neurodegeneration is associated with
      the local release of a neurotransmitter. For Parkinson's disease this would mean
      that the metabolism of dopamine in the striatum, nucleus accumbens and presumably
      the pedunculopontine tegmental nucleus, together with one or more pathological
      factors contribute to the initial neurodegeneration. There are recent studies
      indicating that a transneuronal retrograde degeneration of the substantia nigra
      pars compacta neurons might be induced by a loss of function of dopaminergic
      synapses in the striatum. We have recently established an animal model of
      retrograde striato-nigral degeneration, where the assessment of markers for
      cellular stress is possible. In Parkinson's disease, several structures distal
      from the substantia nigra pars compacta undergo neuropathological changes,
      characterizing the 'secondary neurodegeneration. Our recent studies provide
      experimental evidence for a chronic cellular stress in these structures because
      of a relative or absolute glutamatergic overactivity due to the initial loss of
      dopaminergic innervation. Thus, a loss of dopamine transforms the basal ganglia
      to a 'destructive network'. Both processes, the 'primary' and 'secondary
      neurodegeneration', affecting each other, characterize the progress of chronic
      neurodegeneration. From this point of view, we would further like to develop
      strategies for symptomatic amendment. Excitatory amino acids seem to be involved
      not only in the secondary processes of neurodegeneration, but also in initiation
      of the 'primary degeneration' of the substantia nigra pars compacta. Therefore, a
      reduction of glutamatergic overactivity constitutes a promising neuroprotective
      strategy. Especially the new antagonists of the NMDA-receptors with high affinity
      to the NR2B subunit of the receptor are in focus of our interest, since they
      reveal a favourable profile of side effects, therefore providing a promising tool
      for neuroprotection.

PMID- 16787843
TI  - Prospects for redox-based therapy in neurodegenerative diseases.
AB  - Accumulating evidence supports a primary role for perturbations in redox
      metabolism in the pathogenesis of many neurodegenerative diseases. This evidence
      derives mainly from molecular genetic analysis, direct observation from post
      mortem human brain, and biochemical, pathologic, and therapeutic studies in
      transgenic and other animal models of neurodegeneration. We review here the
      evidence for redox-mediated pathogenesis in neurodegenerative diseases. The
      emerging class of redox-based therapeutic agents is then discussed. Drugs of this
      class are distinguished by their proximate effect, which is oxidative and not
      phosphorylative.

PMID- 16787844
TI  - Review of apoptosis vs. necrosis of substantia nigra pars compacta in Parkinson's
      disease.
AB  - The discovery that melanized neurons of the pars compacta of substantia nigra
      (pcSN) degenerate in the midbrain of human Parkinsonians is nearly a century old,
      but only in this decade have we gained insights into mechanisms underlying this
      neuronal loss. Although it had long been assumed that pcSN neurons underwent
      necrosis, recent (1) in vitro studies on isolated neurons, (2) in vivo studies in
      animals treated with neurotoxins, and (3) postmortem study of human Parkinsonian
      brain provide strong evidence that pcSN cells may be lost more from apoptosis
      (i.e., cell suicide) than from necrosis. This paper gives some historical
      perspective, but focuses primarily on mechanisms involved in both necrosis and
      apoptosis of neurons, primarily dopaminergic, and reviews the recent literature
      relating to apoptosis and apoptotic factors now identified in neurons undergoing
      neurotoxin-induced death and in postmortem human Parkinsonian brain. The weight
      of evidence in favor of apoptosis and apoptotic factors in these neurons,
      provides us with tools needed to develop anti-apoptotic factors that can be
      targeted to proteins on genes, so that it may be possible to decelerate or
      prevent the progressive neuronal cell loss in human Parkinsonians or in humans
      with other neurodegenerative disorders.

PMID- 16787845
TI  - Restoration and putative protection in Parkinsonism.
AB  - Synergistic antiparkinsonian actions of different classes of putative therapeutic
      agents co-administered with a subthreshold dose of L-3,4-dihydroxyphenylalanine
      (L-Dopa) (5 mg/kg) in drug-naive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-treated mice as well as the restorative actions of those compounds in
      suprathreshold L-Dopa-tolerant MPTP-treated mice subjected to "wearing-off" of L
      Dopa efficacy were assessed in a series of experiments. The classes of compounds
      studied included the noncompetitive NMDA antagonists, memantine, amantadine and
      MK-801, the anticonvulsive and putative anticonvulsive agents, lamotrigine, FCE
      26743, phenytoin, the monoamine oxidase inhibitors, L-Deprenyl, amiflamine, alpha
      ethyltryptamine, clorgyline and guanfacine. In this final case, the restorative
      effects of clonidine and guanfacine were antagonized by the alpha(2)-adrenoceptor
      antagonist, yohimbine, but not the alpha(1)-adrenoceptor antagonist, prazosin.
      Within each class of potentially therapeutic agents a differential restorative
      efficacy was obtained, but the combination of different doses of apomorphine with
      clonidine failed to restore motor activity. Finally, the neuroprotective actions
      of acute and subchronic administration of the nitrone spin-trapping compound,
      alpha-phenyl-tert-butyl nitrone upon the spontaneous motor behaviour and striatal
      dopamine concentrations of MPTP-treated mice was examined.

PMID- 16787847
TI  - Effect of different non-chloride sodium sources on the performance of heat
      stressed broiler chickens.
AB  - 1. One hundred and eighty 1-d-old broiler chicks were used to evaluate the effect
      upon broiler performance during severely hot summer months of three different
      sodium salts: sodium bicarbonate (NaHCO3), sodium carbonate (Na2CO3) and sodium
      sulphate (Na2SO4), in starter and finisher diets having an identical electrolyte
      balance (DEB) of 250 mEq/kg. 2. The non-chloride sodium salts were added to
      contribute the same amount of sodium and were substituted at the expense of
      builder's sand in the basal diets containing common salt (NaCl) as Na and Cl
      source. 3. Each diet was fed to three experimental units having 15 chicks each
      until 42 d of age. Severe heat-stress conditions, maintained in the rearing room,
      were indicated by high average weekly room temperature (minimum 29.3 degrees C;
      maximum 38.0 degrees C). 4. Diets containing sodium salts gave better body weight
      gain, feed intake and feed to gain ratio than the control diet. Sodium salts also
      enhanced water intake as well as water to feed intake ratio. This effect was more
      pronounced in broilers fed NaHCO3 supplement (with NaCl in the basal diets). 5.
      The increased water intake resulted in lower body temperature in heat-stressed
      birds fed NaHCO3 supplemented diet than in birds fed other sodium salts. A lower
      mortality rate was noted with NaHCO3 (15.15%), Na2CO3 (13.64%) and Na2SO4
      (15.15%) supplements than with the control (33.33%) treatment. 6. Better carcase
      and parts yield were observed in sodium supplemented broilers. Sodium salts
      reduced the alkalotic pH and enhanced the blood sodium content, which ultimately
      improved the blood electrolyte balance and overall performance of heat-stressed
      broilers. 7. Supplementing broiler diets with sodium salts improved the live
      performance of heat-stressed broilers and better productive performance was noted
      with NaHCO3 than other sodium supplements.

PMID- 16787848
TI  - Leg health and performance of broiler chickens reared in different light
      environments.
AB  - 1. The effects of light source and intensity on leg health and performance of
      female ROSS 308 broiler chickens were investigated in a 2 x 2 experimental design
      (8 groups of 275 chicks) of two light sources (Osram biolux and Osram warm-white)
      and two light intensities (5 and 100 clux, adjusted to fowl-perceived
      illuminance). 2. At 41 d of age, body weight, gait-score, footpad dermatitis and
      hock-burn were measured on 50 birds from each light environment. In addition,
      weekly feed intake and body weight were determined on a group basis and mortality
      was recorded continuously. 3. The light environment did not affect the severity
      of the gait-score or hock-burns. The risk of moderate to severe lameness and hock
      burns increased with body weight. Birds weighing more than 2400 g had an
      increased probability of moderate footpad lesions in biolux light. 4. Weight and
      gait-score, as well as gait-score and hock-burn were positively correlated. Podo
      dermatitis was weakly correlated with hock-burn, which contradicts earlier
      findings. The light environment did not affect feed intake, body weight or
      mortality. 5. The light sources and intensities employed in this study did not
      adversely affect production or leg health of broiler chickens reared semi
      commercially.

PMID- 16787849
TI  - Skeletal muscle fibre growth and growth associated myopathy in the domestic
      chicken (Gallus domesticus).
AB  - 1. Genetic selection of broilers may have pushed muscle fibres to their maximum
      functional size constraints. Broiler (B), female great-grandparent (GGP) and
      layer (L) lines were weighed, blood sampled and killed from 5 to 25 weeks of age.
      2. At 25 weeks, Pectoralis major (Pm) fibre size reached by the B (65.9 microm)
      and GGP (59.8 microm) were 1.5 times greater than the L (38.1 microm). In the B
      and GGP lines, fibre growth of the Pm markedly exceeded that of the Biceps
      femoris (Bf) muscle. However, in the L line, fibre growth of the Pm and Bf muscle
      was comparable. Connective tissue content was generally higher in the Bf than in
      the Pm of all lines. 3. Centralised nuclei were observed predominantly in Pm, and
      may regulate fibre size. Both large muscle fibres and inadequate capillary supply
      may induce metabolic stress in B and GGP lines due to the large diffusion
      distances for oxygen, metabolites and waste products. 4. Enzyme markers of muscle
      damage (creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate
      aminotransaminase (AST)) and histopathological analysis of Pm and Bf indicated
      greater myopathy in B and GGP vs L. 5. Regenerative processes were associated
      with oestrogen secretion. Reduced CK and LDH preceded egg yolk precursor
      production and increased calcium uptake for eggshell synthesis in all three
      lines. Oestrogen may stimulate muscle fibre regeneration and recovery as a myo
      protective adaptation to potentially detrimental changes in calcium economy
      during egg production.

PMID- 16787846
TI  - Neuroprotective strategies in Parkinson's disease: protection against progressive
      nigral damage induced by free radicals.
AB  - Brain undergoes neurodegeneration when excess free radicals overwhelm
      antioxidative defense systems during senescence, head trauma and/or neurotoxic
      insults. A site-specific accumulation of ferrous citrate-iron complexes in the
      substantia nigra dopaminergic neurons could lead to exaggerated dopamine
      turnover, dopamine auto-oxidation, free radical generation, and oxidant stress.
      Eventually, this iron-catalyzed dopamine auto-oxidation results in the
      accumulation of neuromelanin, a progressive loss of nigral neurons, and the
      development of Parkinson's disease when brain dopamine depletion is greater than
      80%. Emerging evidence indicates that free radicals such as hydroxyl radicals ((.
      )OH) and nitric oxide ((.-)NO) may play opposite role in cell and animal models
      of parkinsonism. (.-)OH is a cytotoxic oxidant whereas oNO is an atypical
      neuroprotective antioxidant. (.-)NO and S-nitrosoglutathione (GSNO) protect
      nigral neurons against oxidative stress caused by 1-methyl-4-phenylpyridinium
      (MPP(+)), dopamine, ferrous citrate, hemoglobin, sodium nitroprusside and
      peroxynitrite. MPP(+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), increases the nigral uptake of iron complexes and
      dopamine overflow leading to the generation of (.-)OH, protein oxidation, lipid
      peroxidation, and associated retrograde degeneration. In addition to GSNO, MPP(+)
      induced oxidative neurotoxicity can be prevented by antioxidants including
      selegiline, 7-nitroindazole, 17beta-estradiol, melatonin, alpha-phenyl-tert
      butylnitrone and U78517F. Similar to selegiline, 7-nitroindazole is a MAO-B
      inhibitor, which blocks the bio-activation of MPTP and oxidative stress. Freshly
      prepared but not light exposed, (.-)NO-exhausted GSNO is about 100 times more
      potent than the classic antioxidant glutathione. Via S-nitrosylation, GSNO also
      inhibits proteolysis and cytotoxicity caused by caspases and HIV-1 protease.
      Furthermore, in addition to protection against serum deprivation stress, the
      induction of neuronal NOS1 in human cells increases tolerance to MPP(+)-induced
      neuro-toxicity since newly synthesized (.-)NO prevents apoptosis possibly through
      up-regulation of bcl-2 and down regulation of p66(shc). In conclusion, reactive
      oxygen species are unavoidable by-products of iron-catalyzed dopamine auto
      oxidation, which can initiate lipid peroxidation, protein oxidation, DNA damage,
      and nigral loss, all of which can be prevented by endogenous and exogenous (.
      )NO. Natural and man-made antioxidants can be employed as part of preventative or
      neuroprotective treatments in Parkinson's disease and perhaps dementia complexes
      as well. For achieving neuroprotection and neuro-rescue in early clinical
      parkinsonian stages, a cocktail therapy of multiple neuroprotective agents may be
      more effective than the current treatment with extremely high doses of a single
      antioxidative agent.

PMID- 16787850
TI  - Genetic relationships between feed conversion ratio, growth curve and body
      composition in slow-growing chickens.
AB  - 1. Relationships between feed conversion ratio, growth curve parameters and
      carcase composition were investigated on 1061 chickens from a slow-growing line
      of label-type chickens. The growth curve was modelled with the Gompertz function.
      Individual feed conversion ratio (FCR) was recorded between 8 and 10 weeks of age
      and residual feed consumption (RES) was calculated over the same interval.
      Abdominal fat yield (AFY), breast yield (BRY) and leg yield (LY) were also
      measured on the birds following slaughter at 75 d of age. 2. The means for FCR
      and RES were 3.15 and 0.62 g, respectively. Growth curve parameters were 0.141/d
      for initial specific growth rate (L), 0.031/d for maturation rate (K) and 48.9 d
      for age at inflexion (TI). Mean values for BRY, LY and AFY were 166, 306 and 40
      g/kg, respectively. 3. Heritability of FCR and RES were moderate to high (0.33
      and 0.38 to 0.45). Growth curve parameters and LY were moderately heritable (0.22
      to 0.34) and BRY and AFY were highly heritable (0.50 and 0.66). Genetic
      correlations between growth curve parameters and either FCR or RES were low to
      moderate (-0.31 to 0.51). LY and AFY were highly correlated with FCR (-0.70 and
      0.44) and RES (-0.32 and 0.44) but BRY was not (0.00 and -0.35). These results
      show that indirect selection for feed conversion ratio is possible by using
      growth curve parameters and abdominal fatness, which do not require rearing the
      chickens in cages.

PMID- 16787851
TI  - Physical and sensory characteristics of marinated broiler drumsticks treated with
      lactoperoxidase system and thermal treatment.
AB  - 1. The lactoperoxidase system (LPS) and thermal treatments have been shown to
      inactivate some micro-organisms in foods. However, further studies are needed to
      evaluate whether these treatments influenced the physical and sensory
      characteristics of treated samples. 2. A solution that contained 1% acetic acid
      and 3% salt with pH adjusted to 4 was developed as a standard marinade. The LPS
      consisting of 1 microg/ml lactoperoxidase (LP), 5.9 mM potassium thiocyanate
      (KSCN) and 2.5 mM hydrogen peroxide (H2O2) was added to the marinade for the LPS
      treatments. 3. In the thermal treatment, samples were heated with the marinade
      solution at 58 degrees C for 2 min and then marinated at 4 degrees C for 18 h,
      while the non-thermal treatments were marinated at 4 degrees C for 18 h. 4. For
      sensory evaluation, flavouring agents including 0.3% black pepper and 0.15%
      garlic powder were added to the marinade. For physical evaluation, no flavouring
      agents were added. 5. The results showed that combined LPS and thermal treatment
      did not impair the physical or sensory qualities of the samples. 6. In
      conclusion, marinated broiler drumsticks treated with LPS and thermal treatment
      had acceptable physical and sensory qualities.

PMID- 16787852
TI  - Transmission of Campylobacter spp. in a poultry slaughterhouse and genetic
      characterisation of the isolates by pulsed-field gel electrophoresis.
AB  - 1. Contamination of retail products with Campylobacter spp. during the slaughter
      of poultry is a well-known problem of product hygiene. Mechanical evisceration
      often leads to intestinal rupture and discharge of gut contents, which can
      contain zoonotic and human pathogens. Processes along the slaughter line cause
      aerosols and airborne droplets, containing bacterial loads. 2. To estimate the
      possible transmission routes of intestinal Campylobacter, 36 measurements of the
      bioaerosol (Andersen sampler and SKC BioSampler), 30 cloacal (of three flocks),
      10 equipment and 4 sedimentation samples were tested for the presence of
      Campylobacter species. 3. The results imply that, in addition to contaminated
      equipment, which was Campylobacter-positive in 80% of cases, aerosols with peak
      values of 4.0 x 10(4) (test series 1) and 1.4 x 10(4) (test series 2) CFU/m3 also
      provide a potential vector for horizontal transmission. 4. To explore the genetic
      similarities of isolates from different origins, 18 isolates recovered from air,
      26 cloacal, 8 equipment and 4 sedimentation isolates were analysed by pulsed
      field gel electrophoresis (PFGE), using the restriction enzymes Sma I and Sal I.
      The similarity of cloacal isolates with isolates from equipment, air and
      sediment, suggest that the contamination is of intestinal origin. 5. There were
      direct links between Campylobacter-positive flocks and the presence of the same
      strains in the aerosol of the slaughter hall. Air as a potential source for
      microbial transmission must be taken into account.

PMID- 16787853
TI  - Lipid profile in eggs of Araucana hens compared with Lohmann Selected Leghorn and
      ISA Brown hens given diets with different fat sources.
AB  - 1. In a cross-over trial, the egg cholesterol and fatty acid composition of
      Araucana hens was compared with those of two commercial breeds (Lohmann Selected
      Leghorn and ISA Brown) under two feeding regimes, either high (Hn-3) or low (Ln
      3) in long-chain n-3 fatty acids. 2. The Hn-3 diet was formed by isocaloric
      substitution of animal fat in the control diet (Ln-3) by a dry product containing
      stabilised fish oil with standardised concentrations of eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA). 3. Both breed and diet had influences on
      egg composition, without interactions. 4. The Araucana breed showed lower feed
      intake and lower egg weights than the other two breeds. The yolk weight was
      similar, leading to a much higher yolk:albumen ratio in the Araucana eggs. 5. In
      comparison to commercial breeds, Araucanas produced eggs with higher cholesterol
      content per g of yolk, which was even more pronounced when expressed per g of
      egg, due to the high yolk content of the eggs. The cholesterol content of an egg
      remained unchanged by the diet, irrespective of the dietary fat source. 6.
      Changing to the Hn-3 diet led to greater concentrations of polyunsaturated fatty
      acids (PUFA) and lower concentrations of monounsaturated fatty acids (MUFA)
      contents in the yolk, without a change in the ratio of saturated (SFA) to
      unsaturated fatty acids (UFA). 7. Within the PUFA, the n-3 fatty acids increased
      at the expense of the n-6 fatty acids, indicating a competition between n-3 and n
      6 fatty acids for incorporation in the yolk.

PMID- 16787854
TI  - Effects of dietary metabolisable energy, calcium and phosphorus on bone
      mineralisation, leg weakness and performance of broiler chickens.
AB  - 1. Performance, gait score (GS), tibial dyschondroplasia (TD), and tibia bone
      mineralisation and breaking strength were determined in 2880 male and female Ross
      208 broilers fed on diets with two different concentrations of dietary
      metabolisable energy (ME) (11.00 or 12.00 MJ/kg) and 4 different concentrations
      of available phosphorus (aP) adjusted for dietary ME content (4.0, 4.5, 5.0 or
      5.5 g/kg aP in starter and 3.5, 4.0, 4.5 or 5.0 g/kg aP in finisher diets
      containing 12.00 MJ/kg). 2. Tibia ash, calcium (Ca) and phosphorus (P) contents
      in broilers given diets with low ME (11.00 MJ/kg) were greater than those of
      broilers given diets with higher ME (12.00 MJ/kg). Tibia ash, Ca and P contents
      increased curvilinearly with increasing dietary aP content. The dietary aP level
      had no effect on GS. 3. Dietary concentration of ME or aP had no effect on tibia
      breaking strength. 4. Walking ability, as measured by GS, was negatively
      correlated with the body weight (BW) of tested birds at 23 and 35 d of age, but
      the dietary ME content or aP level had no significant effect on GS at 35 d of
      age. 5. The results indicated that bone mineral content had no clear correlation
      with the walking ability of broilers.

PMID- 16787855
TI  - Phytase effects on the efficiency of utilisation and blood concentrations of
      phosphorus and calcium in Pekin ducks.
AB  - 1. The objective was to study the effects of a supplementation of a 6-phytase
      derived from the Peniophora lycii gene in the White Pekin duck. 2. In two balance
      studies, low-phosphorus (P) diets consisting mainly of maize, solvent extracted
      soybean meal and solvent extracted sunflower meal were supplemented with phytase
      up to concentrations of 1500 U/kg (Study 1) or 2000 U/kg (Study 2). Each diet
      (phytase level) was fed to 8 to 10 individually penned ducks. The intake and
      excretion of each animal was measured for 5 consecutive days when ducks were in
      their third week of life. Responses were described by nonlinear regression. 3.
      Although the basal diets from the two studies were similar in ingredient
      composition, efficiencies of P utilisation (P accretion/P intake x 100) for the
      unsupplemented basal diets were 39% in Study 1 and 30% in Study 2. Phytase
      supplementation significantly improved P utilisation up to levels of about 55% in
      both studies. A plateau in P utilisation with an increase in phytase
      supplementation was achieved in Study 2, but not in Study 1. The enzyme was more
      efficient in Study 2 than in Study 1 at low rates of supplementation. Utilisation
      of calcium (Ca) was significantly improved by phytase supplementation. Accretions
      of P and Ca increased at a constant ratio. 4. In a 5-week growth study, diets
      with an intentionally marginal P level were used. Diets were fed either
      unsupplemented or supplemented with 1000 or 10,000 U/kg of phytase. Eight pens of
      10 sex-separated ducks each (4 pens per sex) were allocated to each dietary
      treatment. 5. Phytase significantly improved the growth of ducks of both sexes
      between d 1 and 21, but not between d 22 and 35. Feed conversion rate was not
      affected by treatment. Blood serum phosphate concentrations, but not calcium,
      were significantly increased by phytase supplementation. Blood concentrations of
      creatinine, aspartate aminotransferase and lactate dehydrogenase remained
      unaffected while alanine aminotransferase was significantly reduced by phytase
      supplementation. 6. It was concluded that the efficacy of a microbial phytase
      varies even under similar experimental conditions. Differences in intrinsic
      phytase activity of maize/soybean meal-based diets may be responsible for this.
      The 6-phytase used has the potential to improve the utilisation of plant P in
      duck feeding. A plateau in response was reached above 1500 U/kg.

PMID- 16787856
TI  - Thermoregulatory capacity and muscle membrane integrity are compromised in
      broilers compared with layers at the same age or body weight.
AB  - 1. The effects of acute heat stress (2 h at 32 degrees C and 75% RH) on body
      temperature and indices of respiratory thermoregulation and skeletal muscle
      function were examined in two divergently selected male grandparent lines of
      broiler and layer-type chickens at two ages (35 and 63 d), or at a similar body
      weight (approximately 2.2 kg). 2. The two chicken lines exhibited markedly
      different baseline blood acid-base and skeletal muscle characteristics. At the
      same age or live weight, birds from the broiler line had significantly higher
      venous blood carbon dioxide tensions associated with lower blood pH. Plasma
      creatine kinase (CK) activities reflecting muscle membrane damage were also
      greatly elevated in the broiler line. 3. Exposure to acute heat stress caused an
      increase in deep body temperature, panting-induced acid-base disturbances and
      elevated plasma CK activity in both lines of chicken, an effect that increased
      with age. The extent of disturbances in acid-base regulation and heat-stress
      induced myopathy were more pronounced in the broiler than the layer line at the
      same age or similar live weights. 4. It is suggested that genetic selection for
      high muscle growth in broiler lines has compromised their capacity to respond to
      an acute thermal challenge, leading to detrimental consequences for muscle
      function. This reduction in heat tolerance may have important implications for
      bird welfare and subsequent meat quality.

PMID- 16787857
TI  - End-weight prediction in broiler growth.
AB  - 1. Two different methods, categorised as input-output and single output models,
      were evaluated for slaughter weight prediction of broiler chickens. The input
      output models included linear and non-linear recursive modelling with a time
      varying model structure, whereas the output models consisted only of empirical
      growth equations and several growth curve fitting techniques. 2. The results
      suggested that a simple linear growth curve fitting method gives the greatest
      accuracy in a prediction horizon of 4 d or less. Error is minimised to an average
      of 0.14% when 4 d of past information is used to fit a line to predict the end
      weight one day ahead.

PMID- 16787858
TI  - Comparative apparent metabolisable energy values of high, medium and low tannin
      varieties of sorghum in cockerel, guinea fowl and quail.
AB  - 1. Nitrogen-corrected apparent metabolisable energy values (AMEN) of three
      varieties of sorghum (white-low tannin, brown-medium tannin and red-high tannin)
      were measured in three species of poultry (cockerel, guinea fowl and Japanese
      quail) by a practical diet replacement (total collection) method. 2. Each variety
      of sorghum was tested at two concentrations (200 and 400 g/kg of reference diet)
      in 6 replications with one cockerel or guinea fowl or two quails per replication.
      The duration of the trial included a 10 d preliminary feeding period (on
      conventional grower diet) followed by a 12 d adaptation period (on reference and
      test diets) and a 3 d balance period (with recording of feed intake and excreta
      output). 3. The calculated AMEN values of different sorghum varieties were: white
      -12.9, 12.8 and 12.7; brown--12.7, 12.3 and 12.6; and red--11.4, 11.1 and 11.6
      MJ/kg for cockerels, guinea fowls and quails, respectively. The mean AMEN value
      of red sorghum (11.3 MJ/kg) was significantly lower than those of brown (12.5
      MJ/kg) or white sorghum (12.8 MJ/kg). A negative correlation was observed between
      tannin concentration and AMEN. 4. There was no significant difference in the AMEN
      values of white, brown and red sorghum varieties to the different poultry
      species. AMEN values of sorghum for the cockerel could, therefore, be used in
      practical feed formulation for guinea fowl and quail.

PMID- 16787859
TI  - Effect of ambient storage of wheat samples on their nutritive value for chickens.
AB  - 1. Two wheat cultivars (Abbott and Equinox) were grown using the same crop
      husbandry conditions. Batches of each cultivar were stored at ambient temperature
      (AT) for 0, 6, 12, 18 or 24 weeks. Those stored at AT for less than 24 weeks were
      then stored at -20 degrees C up to the end of the storage period. The 24 week
      (AT) samples were divided into two lots and one lot was frozen to -20 degrees C
      for 24 h. 2. Each of the 12 wheat samples was included (650 g/kg) in a
      nutritionally complete diet and fed to broiler chickens from 7 to 21 d of age.
      The apparent metabolisable energy (AME) of each sample was determined using a
      rapid bioassay with adult cockerels. 3. The Equinox cultivar sample had a high
      proportion (92/1000) of visibly sprouted grains and had a low Hagberg falling
      number (high amylase activity) and high content of free sugars compared to the
      Abbott sample. There were no major changes in dry matter, free sugar content,
      water extract viscosity or Hagberg falling number due to the different times of
      ambient storage of either of the two wheat cultivar samples. 4. The chickens fed
      on the Abbott cultivar wheat had a greater weight gain, although there were no
      differences in the determined AME of the two wheat cultivars. 5. The Abbott
      sample stored at ambient temperature for 6 weeks had a greater AME than the
      sample given no ambient storage and the samples given 18 and 24 weeks ambient
      storage. There were no significant differences between the Equinox cultivar
      samples. There were no effects of storage time on the growth performance of the
      broiler chickens. 6. The AME of the unfrozen Abbott cultivar was greater than the
      frozen (for 24 h) sample but there was no effect on broiler growth performance.
      This study suggests that, in some wheat samples, there may be a benefit in
      avoiding freezing during storage.

PMID- 16787860
TI  - Vitamin E supplementation reduces dexamethasone-induced oxidative stress in
      chicken semen.
AB  - 1. We examined the effects of supplemental dietary vitamin E (Vit E) on semen
      quality and antioxidative status in male domestic fowls exposed to oxidative
      stress induced by synthetic glucocorticoid, dexamethasone (DEX) injection. 2.
      Thirty-six Egyptian local cross males, 42 weeks old, were housed individually in
      cages in an open-sided building under 16 h light:8 h dark and were provided with
      commercial feed and water ad libitum. Birds were divided into 4 groups: DEX (4
      mg/bird/d), Vit E (200 mg/kg diet), DEX + Vit E (4 mg/bird/d + 200 mg/kg diet,
      respectively) and control, n = 9. All treatments lasted for 7 continuous days. 3.
      Oxidative stress induced by injection of DEX (4 mg/bird/d) resulted in decreased
      sperm count and motility correlated with an increased percentage of dead sperms.
      Vit E (200 mg/kg diet) enhanced sperm count and viability when supplemented to
      stress-induced birds, compared to DEX treatment alone. 4. In seminal plasma, low
      calcium concentration, high lipid peroxidation and reduced activity of
      glutathione peroxidase were associated with the oxidative stress. Vit E reduced
      lipid peroxidation in the seminal plasma. 5. In conclusion, excessive
      supplemental dietary Vit E improved semen quality when cockerels were subjected
      to stress conditions. It increased both sperm count and motility, reduced the
      percentage of dead sperm and enhanced the antioxidative status of seminal plasma.

PMID- 16787861
TI  - Effects of aflatoxin B1 and fumonisin B1 on body weight, antibody titres and
      histology of broiler chicks.
AB  - 1. Our objective was to evaluate the toxic effects of aflatoxin B1 (AFB1) and
      fumonisin B1 (FB1), administered singly or in combination to broilers. 2. Feeds
      were prepared with concentrations equal to 0, 50 and 200 microg AFB1/kg, and/or
      0, 50 and 200 mg FB1/kg, and offered to broiler chicks from 8 to 41 d of age. The
      experimental design was totally randomised, in a 3 x 3 factorial arrangement with
      9 treatments and 12 birds per treatment. Animals were vaccinated against
      Newcastle disease on d 14 of life and killed at 41 d. 3. Compared with controls,
      all mycotoxin-treated groups at 41 d had lower body weight and weight gain, and
      higher relative heart weight. The relative weight of the liver increased only in
      birds fed diets containing 200 mg FB1, singly or in combination with AFB1. 4. At
      35 d, all groups receiving mycotoxin-treated rations had reduced geometrical mean
      antibody titres, with birds from groups fed combinations of AFB1 and FB1/kg
      having even lower values, when compared to the other groups. 5. Histological
      changes were observed only in liver from birds fed mycotoxin-contaminated
      rations, and in kidneys of birds fed the diet containing 200 microg AFB1 and 200
      mg FB1/kg. Main alterations included vacuolar degeneration and cell proliferation
      of bile ducts in the liver, and hydropic degeneration in renal tubules in the
      kidneys. 6. We concluded that AFB1 and FB1 in combination have primarily additive
      effects on body weight, liver structure and immunological response of broilers at
      the concentrations used.

PMID- 16787862
TI  - Comparative study of the photopic spectral sensitivity of domestic ducks (Anas
      platyrhynchos domesticus), turkeys (Meleagris gallopavo gallopavo) and humans.
AB  - 1. The photopic spectral sensitivity of domestic ducks and turkeys was determined
      using an operant psychophysical technique. Spectral sensitivity was determined
      over a range of specified wavelengths, including UVA, between 326 < lambda < 694
      nm and the results were directly compared with human spectral sensitivity
      measured under similar experimental conditions. 2. Domestic ducks and turkeys had
      similar spectral sensitivities to each other, and could perceive UVA radiation,
      although turkeys were more sensitive to UVA than ducks. For both species, peak
      sensitivity was between 544 < lambda < 577 nm, with reduced sensitivity at lambda
      = 508 and 600 nm. Both ducks and turkeys had a very different and broader range
      of spectral sensitivity than the human subjects tested. 3. Spectral sensitivity
      and UVA perception in these avian species are discussed in relation to their
      visual ecology and the mechanisms controlling neural processing of colour
      information.

PMID- 16787863
TI  - DNA test to sex the lesser rhea (Rhea pennata pennata).
AB  - 1. A polymerase-chain-reaction (PCR)-based test was adapted to sex the lesser
      rhea. Feathers instead of blood were used as the source of DNA. 2. The primers
      used allowed the assignment of sex by amplification of Z and W chromosome linked
      sequences. 3. This method proved to be safe, accurate and non-invasive. 4. The W
      chromosome linked fragment was sequenced and compared to other ratite sequences.

PMID- 16787865
TI  - Jaw osteonecrosis associated with use of bisphosphonates and chemotherapy:
      paradoxical complication of treatment of bone lesions in multiple myeloma
      patients.
AB  - It has been demonstrated that bisphosphonate-based supportive therapy
      (pamidronate or zoledronate) reduces skeletal events (onset or progression of
      osteolytic lesions) both in patients with multiple myeloma (MM) and in cancer
      patients with bone metastasis. Bisphosphonates (eg, alendronate) are also
      indicated in the treatment of osteoporosis. Nevertheless, osteonecrosis of the
      jaw (ONJ) has been reported in some patients being treated with bisphosphonates.
      We present a series of 9 MM patients who developed ONJ after treatment with
      bisphosphonates and chemotherapy. All the patients in this case series had
      undergone tooth extraction for recurrent dental abscesses while taking
      bisphosphonates. We also review the diagnostic and therapeutic implications of
      this paradoxical complication associated with treatment of bone lesions in MM.

PMID- 16787867
TI  - Adoptive immunotherapy for Hodgkin's lymphoma.
AB  - Adoptive transfer of tumor-specific T-cells is an attractive strategy for the
      treatment of patients with refractory or relapsed Hodgkin's lymphoma. However,
      Hodgkin's lymphomas possess a range of tumor-evasion mechanisms, which must be
      overcome before the full potential of immunotherapies can be achieved. In this
      article, we discuss the promise of Epstein-Barr virus-specific cytotoxic T
      lymphocytes, the roles of cytokines, and other strategies for overcoming the
      immune-evasion mechanisms in Hodgkin's lymphoma.

PMID- 16787866
TI  - Genomic alterations in Hodgkin's lymphoma.
AB  - Cytogenetic analysis of Hodgkin's lymphoma (HL) is hampered by the scarcity of
      neoplastic cells within a sea of reactive cells. There is accumulating evidence
      that HL represents 2 disease entities, classic HL (cHL) with its morphologic
      variants and nodular lymphocyte predominant HL (NLPHL). This subdivision,
      initially worked out in morphologic and immunohistochemical studies, has been
      further substantiated by molecular cytogenetic investigations. Two recurrent
      chromosomal aberrations, namely gains of 2p13-p16 and 9p24, have been found by
      comparative genomic hybridization analysis in microdissected cells from cHL
      patients as well as in cHL cell lines, but not in NLPHL cells. The available cHL
      cell lines are remarkably heterogeneous in their karyotypes, suggesting profound
      genomic instability leading to numeric chromosomal aberration and multiple
      chromosomal breaks and translocations. In this article, we review genomic
      aberrations that may contribute to the development and maintenance of the
      morphologic and clinical presentation of these beta-cell lymphoma entities.
      Furthermore, we delineate current data on the genomic changes observed in the
      neoplastic cells of HL that are created by epigenetic mechanisms, which are
      alternative mechanisms that regulate the expression of relevant genes.

PMID- 16787868
TI  - Epidemiology and pathologic features of Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) has unique epidemiologic characteristics. The variation in
      incidence according to age, sex, race, socioeconomic status, and histologic
      subtype suggests an etiologic heterogeneity for this tumor. Epidemiologic studies
      have shown that both genetic and environmental factors play a role in the
      pathogenesis of HL. HL is one of the Epstein-Barr virus-associated lymphomas, but
      the oncogenetic mechanism of HL remains to be elucidated. Recent advances in
      molecular biology have revealed the peculiar nature of the nodular lymphocyte
      predominant subtype, and as a result this disease is separated from classic types
      of HL in the new World Health Organization classification. Reed-Sternberg (RS)
      cells and lymphocytic and/or histiocytic (L&H) cells originate from germinal
      center B-cells. Loss of the B-cell phenotype due to down-regulation of several B
      cell-specific transcription factors is characteristic of RS cells in classic HL.

PMID- 16787870
TI  - Stable response after administration of stem cell factor combined with
      granulocyte colony-stimulating factor in aplastic anemia.
AB  - We report successful treatment with 25 microg/kg of recombinant methionyl human
      stem cell factor (SCF) combined with 400 microg/m2 of recombinant human
      granulocyte colony-stimulating factor (G-CSF) in 2 patients with aplastic anemia
      refractory to immunosuppressive therapy. In one patient, hemoglobin levels
      increased from 6.4 g/dL to 11.3 g/dL after 36 weeks of SCF/G-CSF treatment.
      Thereafter, the platelet count (24.0 x 10(9)/L) began to improve without the
      therapy, and as of week 272, the platelet count was 125.0 x 10(9)/L with a
      leukocyte count of 8.4 x 10(9)/L and a hemoglobin level of 12.9 g/dL. In the
      other patient, more than 3 years of SCF/G-CSF treatment ameliorated hemoglobin
      levels and platelet counts from 5.8 g/dL to 15.9 g/dL and 8.0 x 10(9)/L to 50.0 x
      10(9)/L, respectively. After cessation of SCF/G-CSF treatment, the positive
      response was sustained, and the platelet count improved further to 71.0 x 10(9)/L
      as of week 242. These observations suggest the clinical benefit of SCF/G-CSF
      administration to patients with refractory aplastic anemia.

PMID- 16787869
TI  - Molecular pathogenesis of Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is a distinctive lymphoma subtype that accounts for
      approximately 30% of all lymphomas in the Western world and approximately 5% in
      Japan. HL is characterized by the giant multinucleated tumor cells called
      Hodgkin/Reed-Sternberg (H/RS) cells, but the cellular origin had long been
      unknown. Recent investigations have clarified that H/RS cells have a clonally
      rearranged immunoglobulin gene in most cases, but it still seems appropriate to
      differentiate HL from other B-cell neoplasms, because the transforming event
      rather than its cellular origin is more likely to influence the nature of H/RS
      cells. Many questions remain to be answered for comprehensive understanding of
      the pathogenesis of HL. The presence of H/RS cells alone is probably not enough
      for disease onset, but the immune reaction against these cells appears to be
      inevitable for generation of HL. Most HL patients are cured with current
      treatment strategies, but some of them have refractory or recurrent disease, and
      intensified treatment occasionally induces therapy-related secondary
      malignancies. Because the growth and survival of H/RS cells are supported by
      various external stimuli and constitutive intracellular signals, management of HL
      is expected to be one of the best applications of molecule-targeted therapy.

PMID- 16787871
TI  - Chicken egg yolk antibodies specific for the gamma chain of human hemoglobin for
      diagnosis of thalassemia.
AB  - Immunoglobulin Y (IgY) technology was used to generate anti-hemoglobin Bart's (Hb
      Bart's) IgY antibodies (Abs) for development into an enzyme-linked immunosorbent
      assay (ELISA) test for thalassemia diagnosis. Hb Bart's purified from the
      hemolysate of a patient with Hb Bart's hydrops fetalis (homozygous alpha
      thalassemia) was used to immunize a chicken via the pectoralis muscle. After
      water dilution and sodium sulfate precipitation, 40 to 70 mg of IgY could be
      extracted from an egg. IgY, first detected in sera 2 weeks after immunization,
      reached the highest titer at week 4, and the titer remained stable for at least 2
      weeks before declining. The pattern of Ab response in the yolk was the same as in
      the serum but was somewhat delayed. The IgY Abs produced reacted with gamma
      globin, Hb Bart's, Hb F, normal cord hemolysate (Hbs F plus A), and Hb Bart's
      hydrops fetalis (Hbs Bart's plus Portland) and to a lesser degree with beta
      globin, Hb A, Hb A2 and adult hemolysate (Hbs A plus A2), but the Abs did not
      react with alpha globin. Immunoaffinity purification with Hb A coupled to
      Sepharose was used to isolate an unbound IgY that reacted with Hb F, Hb Bart's,
      and gamma globin, and this IgY was used to develop an ELISA test for thalassemia
      diagnosis. The results of direct ELISA analyses of 336 hemolysate samples from
      individuals with various known thalassemia genotypes and phenotypes and from
      healthy individuals confirmed the specificity of the polyclonal Abs for Hbs
      containing Hb F and Hb Bart's. This specificity, which was due to the Abs' strong
      reactivity in cases of pathologic thalassemic diseases and weak reactivity in
      cases of nonpathologic thalassemic diseases, depended on the levels of Hb Bart's
      and Hb F.

PMID- 16787873
TI  - Classic polyarteritis nodosa presenting rare clinical manifestations in a patient
      with hemophilia A.
AB  - A 35-year-old patient with hemophilia A presented with rapidly progressive
      polyarteritis nodosa (PAN). He had been infected with hepatitis B virus (HBV) by
      repeated transfusion and was positive for hepatitis B surface antigen but
      negative for hepatitis B surface antibody. The patient presented symptoms of
      acute epididymitis followed by emergency admission because of acute appendicitis.
      On day 7 of admission, he complained of severe back pain, and computerized
      tomography (CT) showed massive perirenal hematoma. On day 49, mild monoplegia in
      the left arm suddenly developed, and CT and magnetic resonance imaging revealed
      multiple cerebral infarctions. Factor VIII replacement therapy was attenuated;
      however, cerebral infarction was progressive and extended throughout the cerebral
      hemispheres. He was diagnosed with classic polyarteritis nodosa (cPAN), and pulse
      methylprednisolone was continued. The patient died of supratentorial herniation,
      and autopsy revealed that vasculitis associated with intimal thickening was
      present in the liver, pancreas, intestine, kidneys, and larger-sized cerebral
      arteries. The development of cPAN appeared to have originated from chronic HBV
      infection, and this is the first report of cPAN in hemophilia patients.
      Concomitant hemorrhagic and thrombotic manifestations of cPAN are hardly
      treatable in patients with coagulation disorders, and the current case may
      represent a rare transfusion-related complication in hemophilia patients.

PMID- 16787872
TI  - High titer of ADAMTS13 inhibitor associated with thrombotic microangiopathy of
      the gut and skeletal muscle after allogeneic hematopoietic stem cell
      transplantation.
AB  - Transplantation-associated thrombotic microangiopathy (TMA) is one of the main
      complications after hematopoietic stem cell transplantation (HSCT). At the time
      of onset of gut TMA, a patient developed a high titer of an inhibitor of the non
      immunoglobulin G type to ADAMTS13, which physiologically hydrolyzes von
      Willebrand factor to control spontaneous intravascular thrombus formation. The
      patient developed symptoms of myositis, a disorder that has occasionally been
      reported to manifest after HSCT and to resemble some idiopathic autoimmune
      diseases. However, a muscle biopsy specimen presented pathologic findings of TMA,
      including microvascular platelet thrombus formation, without inflammatory
      lymphocyte infiltration. ADAMTS13 activities returned to normal after steroid
      treatment, and the improvement of TMA symptoms followed. This patient appears to
      represent a rare case of post-HSCT TMA associated with the development of an
      ADAMTS13 inhibitor.

PMID- 16787874
TI  - A novel mutation W252X in the WAS gene in a Korean patient with Wiskott-Aldrich
      syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder
      characterized by recurrent infection, eczema, and microthrombocytopenia. WAS is
      inherited in an X-linked recessive pattern, and various mutations in the WAS gene
      on the X chromosome are the genetic basis of WAS. A 7-month-old Korean boy
      presented with recurrent bloody diarrhea, eczema, and persistent thrombocytopenia
      with small platelets. Direct sequence analysis of the entire coding region of the
      WAS gene showed a novel nonsense mutation with a G-to-A substitution at the
      nucleotide position 756 on exon 8, leading to a premature termination at codon
      252 (c.756G>A; p.W252X). Family study revealed that neither of the parents had
      the mutation, indicating the de novo occurrence of the mutation.

PMID- 16787875
TI  - Adult T-cell leukemia in a liver transplant recipient that did not progress after
      onset of graft rejection.
AB  - A liver allograft recipient developed acute-type adult T-cell leukemia (ATL)
      during tacrolimus treatment, 2 years after undergoing transplantation for
      subacute fulminant hepatitis. Both donor and recipient were asymptomatic carriers
      of human T-cell lymphotropic virus type I (HTLV-I), but the ATL cells originated
      from the recipient. Tacrolimus treatment was discontinued, and combination
      chemotherapy was administered. The patient achieved complete remission, but the
      transplanted liver was acutely and chronically rejected. The patient did not
      respond to rescue therapy with tacrolimus, prednisolone, and mycophenolate
      mofetil and died of hepatic failure. Liver biopsies showed CD4+ ATL cell
      infiltration at the onset of ATL but not at the terminal stage. Moreover,
      Southern blotting revealed clonal integration of HTLV-I into the host genome of
      lymphoma cells at onset but not at the terminal stage. ATL after liver
      transplantation has not been previously described. The clinical course of the
      posttransplantational ATL was atypical, because it did not progress after the
      onset of rejection.

PMID- 16787876
TI  - Molecular analysis of chronic eosinophilic leukemia with t(4;10) showing good
      response to imatinib mesylate.
AB  - A 38-year-old Japanese man was referred to our hospital in June 2003 for
      treatment of acute respiratory failure with severe eosinophilia. Idiopathic
      hypereosinophilic syndrome had been diagnosed in 1994. However, karyotypic
      examination of bone marrow cells revealed that chromosomal translocation with
      t(4;10)(q12;p11) had occurred in 2000, and chronic eosinophilic leukemia was
      diagnosed. At admission, the patient's respiratory condition was extremely
      serious, and mechanical support was necessary. Despite treatment with steroid
      pulse therapy and cytarabine, the blood eosinophil count did not decrease, and
      the patient's respiratory condition worsened. After obtaining informed consent,
      we administered imatinib mesylate at a dose of 200 mg/day for 2 days and 100
      mg/day for 3 days. The blood eosinophil count decreased dramatically over 5 days,
      and the patient's condition rapidly improved, such that the patient could be
      discharged. In this case, we performed molecular analysis using peripheral blood.
      The FIP1-like 1 (FIP1L1)-platelet-derived growth factor receptor alpha
      (PDGFRalpha) fusion transcript was found with the reverse transcriptase
      polymerase chain reaction analysis. In this case, eosinophilia was possibly
      caused by constitutive activation of tyrosine kinase produced by the FIP1L1
      PDGFRalpha fusion transcript.

PMID- 16787877
TI  - Clinical features of polycythemia vera and essential thrombocythemia in Japan:
      retrospective analysis of a nationwide survey by the Japanese Elderly Leukemia
      and Lymphoma Study Group.
AB  - We conducted the first nationwide survey to clarify the clinical features,
      treatment methods, and prognoses for polycythemia vera (PV) and essential
      thrombocythemia (ET). A 1-page questionnaire was mailed to members of the
      Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG). Surveys on 647
      patients (PV, 266 patients; ET, 381 patients) were returned and analyzed.
      Thrombotic events at diagnosis and during follow-up occurred at rates of 15.4%
      and 8.5%, respectively, in PV cases and 17.6% and 8.7% in ET cases. Splenomegaly
      was observed in only 28.8% of PV patients and 10.8% of ET patients. The leukocyte
      alkaline phosphatase score was elevated in only 46.2% of PV patients. The
      incidences of abnormal karyotypes were less than 10% in both PV and ET cases. The
      rates of transformation to myelofibrosis were 2.6% in both PV and ET cases, and
      acute leukemia was noted in 1.1% of PV patients and 2.9% of ET patients.
      Prognostic factors were thrombotic history for PV and thrombotic history and age
      (>or=60 years) for ET. The present study clearly demonstrated clinical
      differences between Japanese and Western patients for PV and ET. Concerning the
      treatment of PV and ET, the study revealed considerable variation among Japanese
      hematologists. These results suggest the necessity of developing treatment
      guidelines according to risk stratification that are suitable for Japanese PV and
      ET patients.

PMID- 16787878
TI  - Successful treatment of refractory peripheral T-cell lymphoma with a combination
      of fludarabine and cyclophosphamide.
AB  - We report a case of refractory peripheral T-cell lymphoma (PTCL) successfully
      treated with a combination of fludarabine and cyclophosphamide (FLU/CY). A 68
      year-old man with concurrent PTCL and diffuse large B-cell lymphoma was treated
      effectively with 3-course CHOP (cyclophosphamide, doxorubicin, vincristine, and
      prednisolone) therapy, but PTCL relapse occurred and was resistant to ESHAP
      (etoposide, methylprednisolone, cytarabine, and cisplatin) therapy. FLU/CY
      therapy led to complete remission, which was maintained for almost 14 months
      after a single course. We concluded that a FLU/CY regimen may be useful for
      attaining long-term remission in patients with refractory relapsed PTCL and
      should therefore be considered a valuable treatment choice.

PMID- 16787879
TI  - Treatment with candesartan combined with angiotensin-converting enzyme inhibitor
      for immunosuppressive treatment-resistant nephrotic syndrome after allogeneic
      stem cell transplantation.
AB  - Most cases of nephrotic syndrome following stem cell transplantation (SCT) occur
      6 months after SCT. The patients are treated with immunosuppressive therapies;
      however, in some cases treatment is not effective. We used enalapril, an
      angiotensin-converting enzyme inhibitor (ACEI) and candesartan, an angiotensin II
      receptor blocker (ARB), for the control of proteinuria in a case of
      immunosuppressive treatment (IST)-resistant nephrotic syndrome. A 15-year-old boy
      with acute lymphoblastic leukemia underwent allogeneic peripheral blood SCT from
      a completely HLA-matched sibling after completion of a conditioning regimen
      composed of 12-Gy doses of total-body irradiation, 600 mg/m2 thiotepa, and 140
      mg/m2 melphalan. Twenty-eight months after SCT, minimal-change nephrotic syndrome
      was diagnosed on the basis of biopsy findings. Although neither cyclosporine
      (trough level, 100-150 ng/mL) nor corticosteroid was effective, proteinuria
      disappeared 2 months after the beginning of treatment with tacrolimus (trough
      level, 13-20 ng/mL), and remission was maintained for 23 months. Nephrotic
      syndrome recurred, however, and was resistant to tacrolimus. Findings at the
      second renal biopsy revealed membranous nephropathy. An ARB (candesartan, 4 mg/
      day) in combination with an ACEI (enalapril, 5 mg/day) was started. Proteinuria
      improved within 2 weeks. We suggest that ARB combined with ACEI can be used to
      control proteinuria in patients with IST-resistant nephrotic syndrome after SCT.

PMID- 16787880
TI  - Calcineurin inhibitor-induced irreversible neuropathic pain after allogeneic
      hematopoietic stem cell transplantation.
AB  - The calcineurin inhibitors (CIs) cyclosporine A and tacrolimus are essential for
      graft-versus-host disease prophylaxis but are associated with adverse effects,
      including neurotoxicity. We report a case of irreversible CI-induced neuropathic
      pain following allogeneic hematopoietic stem cell transplantation. The patient
      developed dysesthesia, electric shock-like pain, and severe itching followed by
      intractable analgesic-resistant pain in the lower extremities. There were no
      abnormal radiographic findings, and there was no improvement with a reduction of
      CI dosage or with administration of a calcium channel blocker. These clinical
      findings are similar to but inconsistent with CI-induced musculoskeletal pain
      syndromes previously reported in organ transplantation.

PMID- 16787881
TI  - Recurrent mutations of factor XI gene in Japanese.

PMID- 16787882
TI  - A case of non-Hodgkin's lymphoma and invasive thymoma treated with R-CHOP
      therapy.

PMID- 16787883
TI  - Severe hemorrhage from gastric vascular ectasia developed in a patient with AML.

PMID- 16787884
TI  - Pneumatosis coli after thalidomide treatment.

PMID- 16787885
TI  - Coalescence of psychiatry, neurology, and neuropsychology: from theory to
      practice.
AB  - In a climate of renewed interest in the synergy between neurology and psychiatry,
      practitioners are increasingly recognizing the importance of exchange and
      collaboration between these two disciplines. However, there are few working
      models of interdisciplinary teams that freely share expertise in real time, while
      providing clinical and academic training to future physicians who specialize in
      the central nervous system. Over the past 11 years, the McLean Hospital
      Neuropsychiatry and Behavioral Neurology service has provided proof-of-principle
      for such collaboration, demonstrating that a team comprising psychiatrists,
      neurologists, and neuropsychologists can function effectively as a unit while
      maintaining the autonomy of these three disciplines and also synthesizing their
      combined knowledge. In addition to delivering enhanced patient care and promoting
      medical research, this clinical service has provided enriched cross-specialty
      training for fellows, residents, and medical students. The practical functioning
      of the team is described, and case vignettes are presented to illustrate the
      team's collaborative synergism in practice.

PMID- 16787886
TI  - Adjustment for whole brain and cranial size in volumetric brain studies: a review
      of common adjustment factors and statistical methods.
AB  - In this article we address analytic challenges inherent in brain volumetrics
      (i.e., the study of volumes of brains and brain regions). It has sometimes been
      assumed in the literature that deviations in regional brain size in clinical
      samples are directly related to maldevelopment or pathogenesis. However, this
      assumption may be incorrect; such volume differences may, instead, be wholly or
      partly attributable to individual differences in overall dimension (e.g., for
      head, brain, or body size). What quantitative approaches can be used to take
      these factors into account? Here, we provide a review of volumetric and
      nonvolumetric adjustment factors. We consider three examples of common
      statistical methods by which one can adjust for the effects of body, head, or
      brain size on regional volumetric measures: the analysis of covariance, the
      proportion, and the residual approaches. While the nature of the adjustment will
      help dictate which method is most appropriate, the choice is context sensitive,
      guided by numerous considerations-chiefly the experimental hypotheses, but other
      factors as well (including characteristic features of the disorder and sample
      size). These issues come into play in logically framing the assessment of
      putative abnormalities in regional brain volumes.

PMID- 16787887
TI  - Side effects of atypical antipsychotics: extrapyramidal symptoms and the
      metabolic syndrome.
AB  - In this article we examine the two major classes of side effects with atypical
      antipsychotics: extrapyramidal symptoms (EPS) and the metabolic syndrome (the
      triad of diabetes, dyslipidemia, and hypertension, with associated obesity). We
      conclude that atypical antipsychotics continue to have notable risks of EPS,
      particularly akathisia, and that these agents also appear to increase the risk of
      the metabolic syndrome, though this effect seems most marked with clozapine and
      olanzapine. Novel conclusions based on this review are as follows: we provide a
      classification scheme based on low versus high D2 binding affinity (which is, to
      our knowledge, a new means of classifying atypical antipsychotics); we emphasize
      that the akathisia risk is likely equal among agents and that tardive dyskinesia
      is an early, and not late, risk in treatment (a common misconception); we make
      the methodological point that in randomized clinical trials, there is a high risk
      of false-negatives regarding side effects; we raise the issue of confounding bias
      in epidemiological studies of metabolic syndrome; and we stress the need to
      compare side effects in the same studies and not different studies. Future
      prospective observational cohort studies must target side effects and be designed
      to collect and analyze data on confounding factors.

PMID- 16787888
TI  - From zero to a hundred in a split second: understanding aggression in an eight
      year-old child.

PMID- 16787889
TI  - The case of the missing defendant: medical testimony in trials of the
      unconscious.

PMID- 16787890
TI  - Traditional toxicity documentation of Chinese Materia Medica--an overview.
AB  - Documentation of Chinese materia medica (CMM) dates back to around 1,100 BC when
      only dozens of drugs were first described. By the end of the 16th century, the
      number of drugs documented had reached close to 1,900. And by the end of the last
      century, published records of CMM have reached 12,800 drugs. The recorded
      traditional information includes toxicities, incompatibilities, cautions,
      precautions and contraindications. Thus, contrary to a general misconception,
      toxicity data on Chinese herbs exist and are not meager. If consulted properly
      before embarking on a study of CMM, it will save researchers much time and
      efforts and the frustration of not obtaining consistent or expected results. The
      history of documentation is reviewed with examples of major classic and
      contemporary works highlighting and emphasizing the manner in which CMM
      toxicities have traditionally been documented through clinical experience as
      opposed to most modern toxicity data that are based on animal experimentation.

PMID- 16787891
TI  - Enhancing generalized teaching strategy use in daily routines by parents of
      children with autism.
AB  - PURPOSE: The purpose of this study was to examine the effects of facilitating
      generalized use of teaching strategies by parents of children with autism within
      daily routines. METHOD: Five preschool children with autism participated in
      intervention with a parent within daily routines in the family's home. Parents
      learned to include 2 teaching strategies in target routines to address their
      child's communication objectives. Parent-child interactions in routines were
      videotaped for data coding and analysis. Proactive programming of generalization
      occurred by systematic selection of intervention routines and by embedding
      intervention in multiple routines. Generalization data were collected by
      measuring strategy use in untrained routines. A multiple baseline design across
      teaching strategies was used to assess experimental effects. RESULTS: All parents
      demonstrated proficient use of teaching strategies and generalized their use
      across routines. The intervention had positive effects on child communication
      outcomes. All parents perceived the intervention to be beneficial. CONCLUSION:
      Results from this study add to the limited body of evidence supporting parent
      implemented interventions in natural environments with young children with autism
      spectrum disorder. Additional research that replicates this approach with
      children of varying ages and disabilities and families with diverse
      characteristics is needed to support the generality of these findings.

PMID- 16787892
TI  - The development of proto-performative utterances in deaf toddlers.
AB  - PURPOSE: The purpose of this study was to examine and compare the development of
      proto-imperative and proto-declarative utterances in normally developing, non
      neonatally screened, profoundly deaf toddlers. METHOD: Both types of proto
      declarative are considered to be the most basic prelinguistic and early
      linguistic communicative functions. Eighteen normally developing, non-neonatally
      screened, profoundly deaf toddlers participated in a longitudinal study. All
      children were enrolled in the same oral-aural home guidance program. At the time
      of the study, none of the children had received a cochlear implant. At the ages
      of 18, 24, and 30 months, proto-imperative utterances were elicited using an
      adapted version of M. Casby and J. A. Cumpata's (1986) Protocol for the
      Assessment of Prelinguistic Intentional Communication. For eliciting proto
      declarative intentions, a video clip was used. RESULTS: Results revealed a
      significant increase in both frequency and level of utterances for both types of
      proto-performatives. Although there was a clear development from nonlinguistic
      toward linguistic communication, utterances remained predominantly deictic
      gestural for the imperative intentions and referential-gestural for declaratives.
      CONCLUSIONS: The data support the notion from the literature that both types of
      performatives are susceptible to elicitation. Results also suggest that after
      neonatal screening, both total communication and oral-aural approaches might
      accelerate conventionalization of the earliest communicative utterances of
      profoundly deaf toddlers.

PMID- 16787893
TI  - Speech, prosody, and voice characteristics of a mother and daughter with a 7;13
      translocation affecting FOXP2.
AB  - PURPOSE: The primary goal of this case study was to describe the speech, prosody,
      and voice characteristics of a mother and daughter with a breakpoint in a
      balanced 7;13 chromosomal translocation that disrupted the transcription gene,
      FOXP2 (cf. J. B. Tomblin et al., 2005). As with affected members of the widely
      cited KE family, whose communicative disorders have been associated with a point
      mutation in the FOXP2 gene, both mother and daughter had cognitive, language, and
      speech challenges. A 2nd goal of the study was to illustrate in detail, the types
      of speech, prosody, and voice metrics that can contribute to phenotype sharpening
      in speech-genetics research. METHOD: A speech, prosody, and voice assessment
      protocol was administered twice within a 4-month period. Analyses were aided by
      comparing profiles from the present speakers (the TB family) with those from 2
      groups of adult speakers: 7 speakers with acquired (with one exception) spastic
      or spastic-flaccid dysarthria and 14 speakers with acquired apraxia of speech.
      RESULTS: The descriptive and inferential statistical findings for 13 speech,
      prosody, and voice variable supported the conclusion that both mother and
      daughter had spastic dysarthria, an apraxia of speech, and residual developmental
      distortion errors. CONCLUSION: These findings are consistent with, but also
      extend, the reported communicative disorders in affected members of the KE
      family. A companion article (K. J. Ballard, L. D. Shriberg, J. R. Duffy, & J. B.
      Tomblin, 2006) reports information from the orofacial and speech motor control
      measures administered to the same family; reports on neuropsychological and
      neuroimaging findings are in preparation.

PMID- 16787895
TI  - The production of finite and nonfinite complement clauses by children with
      specific language impairment and their typically developing peers.
AB  - The purpose of this study was to explore whether 13 children with specific
      language impairment (SLI; ages 5;1-8;0 [years;months]) were as proficient as
      typically developing age- and vocabulary-matched children in the production of
      finite and nonfinite complement clauses. Preschool children with SLI have marked
      difficulties with verb-related morphology. However, very little is known about
      these children's language abilities beyond the preschool years. In Experiment 1,
      simple finite and nonfinite complement clauses (e.g., The count decided that
      Ernie should eat the cookies; Cookie Monster decided to eat the cookies) were
      elicited from the children through puppet show enactments. In Experiment 2,
      finite and nonfinite complement clauses that required an additional argument
      (e.g., Ernie told Elmo that Oscar picked up the box; Ernie told Elmo to pick up
      the box) were elicited from the children. All 3 groups of children were more
      accurate in their use of nonfinite complement clauses than finite complement
      clauses, but the children with SLI were less proficient than both comparison
      groups. The SLI group was more likely than the typically developing groups to
      omit finiteness markers, the nonfinite particle to, arguments in finite
      complement clauses, and the optional complementizer that. Utterance-length
      restrictions were ruled out as a factor in the observed differences. The authors
      conclude that current theories of SLI need to be extended or altered to account
      for these results.

PMID- 16787894
TI  - Early effects of responsivity education/prelinguistic milieu teaching for
      children with developmental delays and their parents.
AB  - PURPOSE: To evaluate the efficacy of a 6-month course of responsivity
      education/prelinguistic milieu teaching (RE/PMT) for children with developmental
      delay and RE/PMT's effects on parenting stress in a randomized clinical trial.
      METHOD: Fifty-one children, age 24-33 months, with no more than 10 expressive
      words or signs, were randomly assigned to treatment/no-treatment groups. Thirteen
      children in each group had a diagnosis of Down syndrome. RESULTS: In 1 of 2
      multivariate comparisons, the RE/PMT group exhibited superior gains in
      communication compared with the no-treatment group. The treatment effect for
      overall use of intentional communication acts in the child-examiner context was
      significant (d = .68, 95% confidence interval = 0.12-1.24). There were no effects
      on child outcomes due to presence or absence of Down syndrome. RE/PMT led to
      modest increases in recoding of child acts by parents of children who did not
      have Down syndrome. There were no effects on parenting stress associated with the
      intervention or the presence or absence of Down syndrome. CONCLUSIONS: RE/PMT may
      be applied clinically with the expectation of medium-size effects on the child's
      rate of intentional communication acts after 6 months of intervention. The
      approach warrants further investigation with modifications, such as delivery at
      higher intensity levels.

PMID- 16787896
TI  - Lexical-semantic organization in bilingual children: evidence from a repeated
      word association task.
AB  - PURPOSE: This study examined lexical-semantic organization of bilingual children
      in their 2 languages and in relation to monolingual age-mates. METHOD: Twelve
      Mandarin-English bilingual and 12 English monolingual children generated 3
      associations to each of 36 words. Responses were coded as paradigmatic (dog-cat)
      or syntagmatic (dog-bark). RESULTS: Within the bilingual group, word association
      performance was comparable and correlated between 1st and 2nd languages.
      Bilingual and monolingual children demonstrated similar patterns of responses,
      but subtle group differences were also revealed. When between-group comparisons
      were made on English measures, there was a bilingual advantage in paradigmatic
      responding during the 1st elicitation and for verbs. CONCLUSION: Results support
      previous studies in finding parallel development in bilinguals' 1st- and 2nd
      language lexical-semantic skills and provide preliminary evidence that
      bilingualism may enhance paradigmatic organization of the semantic lexicon.

PMID- 16787898
TI  - Complementing behavioral measures with electrophysiological measures in
      diagnostic evaluation: a case study in two languages.
AB  - This case study focuses on a bilingual, older man who spoke Polish and English
      and showed weaknesses on clinical measures of dichotic listening in English. It
      was unclear whether these test results were influenced by the participant's
      facility with his second language or by other nonauditory factors. To elucidate
      the nature of this deficit, the authors examined behavioral and
      electrophysiological responses during dichotic-listening tasks involving
      linguistic processing in both languages. A diotic (control) condition was
      included to examine whether nonauditory factors, such as language familiarity,
      memory, or decline in speed of mental processing, might explain the dichotic
      results. The results from this participant were compared with those obtained from
      a bilingual young adult who also spoke both Polish and English. Results showed a
      substantial left-ear deficit for the older individual on both behavioral and
      electrophysiological measures of dichotic listening. The pattern of results is
      consistent with previous findings in demonstrating that the left-ear deficit in
      this patient derived from an auditory-specific defect rather than from any of the
      extra-auditory factors associated with language facility or cognitive decline.

PMID- 16787897
TI  - Action naming in Spanish and English by sequential bilingual children and
      adolescents.
AB  - PURPOSE: Verb processing in early sequential Spanish-English bilinguals was
      investigated. Primary study goals were to identify potential patterns of
      development in relative levels of verb processing efficiency in a 1st (L1) and
      2nd (L2) language and to investigate factors influencing cognitive control of the
      dual-language system in developing bilinguals. METHOD: Four age groups of early
      sequential Spanish-English bilinguals (5-7 years, 8-10 years, 11-13 years, and 14
      16 years of age) named action pictures in single-language (Spanish or English)
      and mixed-language (alternating Spanish and English) conditions. Dependent
      variables were accuracy and response time (RT). RESULTS: Action-naming
      proficiency improved in both L1 and L2 with age, with a shift from L1 to L2
      dominance in accuracy. In comparison with the single-language condition, the
      mixed-language condition engendered slower RT for all age groups and lower
      accuracy for the 3 younger age groups. The oldest age group did not show accuracy
      difference between the conditions. CONCLUSIONS: These general patterns of verb
      processing across age, language, and processing conditions replicated and
      enriched previous findings of noun processing in similar populations (K. J.
      Kohnert, E. Bates, & A. E. Hernandez, 1999). However, verb processing was
      considerably slower and less accurate than noun processing. Theoretical and
      applied implications of these findings are discussed.

PMID- 16787899
TI  - The effects of high-frequency amplification on the objective and subjective
      performance of hearing instrument users with varying degrees of high-frequency
      hearing loss.
AB  - PURPOSE: The purpose of the present study was to determine if amplifying beyond 2
      kHz affected the objective and subjective performance of hearing instrument users
      with varying degrees of mild-to-severe high-frequency sensorineural hearing loss.
      METHOD: Twenty participants were fitted binaurally with digital completely-in-the
      canal devices with 4-channel wide dynamic range compression (Starkey Axent). Each
      participant used the hearing instruments for two 6-week trial periods. Each
      hearing instrument was programmed to maximize high-frequency audibility during 1
      trial period and minimize high-frequency audibility during the other trial
      period. Objective evaluations were conducted in quiet using the Connected Speech
      Test (CST) and in noise using the CST and the Hearing in Noise Test. Subjective
      performance was evaluated by administering the Abbreviated Profile of Hearing Aid
      Benefit and a questionnaire. RESULTS: Results indicated that high-frequency
      amplification significantly improved objective performance in noise and
      subjective preference in quiet for listeners with varying degrees of mild-to
      severe high-frequency hearing loss. Results also suggested that high-frequency
      amplification may affect subjective preference in noise and overall for listeners
      with varying degrees of mild-to-severe high-frequency hearing loss when feedback
      is eliminated. CONCLUSION: Based on these significant benefits, dispensers should
      be aware that high-frequency amplification should, at least initially, be
      provided to the affected high-frequency regions when mild-to-severe hearing loss
      is present.

PMID- 16787900
TI  - Evaluation of an audiovisual-FM system: investigating the interaction between
      illumination level and a talker's skin color on speech-reading performance.
AB  - A program designed to evaluate the benefits of an audiovisual-frequency modulated
      (FM) system led to some questions concerning the effects of illumination level
      and a talker's skin color on speech-reading performance. To address those issues,
      the speech of a Caucasian female was videotaped under 2 conditions: a light skin
      color condition and a dark skin color condition. For the latter condition, makeup
      was applied to the talker's face. For both skin color conditions, the talker was
      recorded while speaking sentences under 7 different levels of illumination: 2, 3,
      4, 16, 60, 256, and 600 footcandles (fc). Fifteen participants completed the
      speech perception task in a visual-only modality. The results revealed a
      significant interaction of illumination level and skin color. For the light skin
      color condition, speech-reading performance improved systematically as the
      illumination level increased from 3 to 16 fc. For the dark skin color condition,
      no differences in speech-reading performance were observed between the 2-fc and
      the 3-fc conditions. However, a large improvement in speech-reading performance
      was observed as the illumination level increased from 4 fc to 16 fc. It is
      speculated that in addition to an overall effect of illumination level, the
      contrast in luminance at the level of the talker's face has an effect on speech
      reading performance.

PMID- 16787901
TI  - The relationship of vocal loudness manipulation to prosodic F0 and durational
      variables in healthy adults.
AB  - This investigation was motivated by observations that when persons with
      dysarthria increase loudness their speech improves. Some studies have indicated
      that this improvement may be related to an increase of prosodic variation.
      Studies have reported an increase of fundamental frequency (F0) variation with
      increased loudness, but there has been no examination of the relation of loudness
      manipulation to specific prosodic variables that are known to aid a listener in
      parsing out meaningful information. This study examined the relation of vocal
      loudness production to selected acoustic variables known to inform listeners of
      phrase and sentence boundaries: specifically, F0 declination and final-word
      lengthening. Ten young, healthy women were audio-recorded while they read aloud a
      paragraph at what each considered normal loudness, twice-normal loudness, and
      half-normal loudness. Results showed that there was a statistically significant
      increase of F0 declination, brought about by a higher resetting of F0 at the
      beginning of a sentence and an increase of final-word lengthening from the half
      normal loudness condition to the twice-normal loudness condition. These results
      suggest that when some persons with dysarthria increase loudness, variables
      related to prosody may change, which in turn contributes to improvement in
      communicative effectiveness. However, until this procedure is tested with
      individuals who have dysarthria, it is uncertain whether a similar effect would
      be observed.

PMID- 16787902
TI  - Influences of electromagnetic articulography sensors on speech produced by
      healthy adults and individuals with aphasia and apraxia.
AB  - PURPOSE: This study examined whether the intraoral transducers used in
      electromagnetic articulography (EMA) interfere with speech and whether there is
      an added risk of interference when EMA systems are used to study individuals with
      aphasia and apraxia. METHOD: Ten adult talkers (5 individuals with
      aphasia/apraxia, 5 controls) produced 12 American English vowels in /hVd/ words,
      the fricative-vowel (FV) words (/si/, /su/, /ei/, /eu/), and the sentence She had
      your dark suit in greasy wash water all year, in EMA sensors-on and sensors-off
      conditions. Segmental durations, vowel formant frequencies, and fricative
      spectral moments were measured to address possible acoustic effects of sensor
      placement. A perceptual experiment examined whether FV words produced in the
      sensors-on condition were less identifiable than those produced in the sensors
      off condition. RESULTS: EMA sensors caused no consistent acoustic effects across
      all talkers, although significant within-subject effects were noted for a small
      subset of the talkers. The perceptual results revealed some instances of sensor
      related intelligibility loss for FV words produced by individuals with aphasia
      and apraxia. CONCLUSIONS: The findings support previous suggestions that acoustic
      screening procedures be used to protect articulatory experiments from those
      individuals who may show consistent effects of having devices placed on intraoral
      structures. The findings further suggest that studies of fricatives produced by
      individuals with aphasia and apraxia may require additional safeguards to ensure
      that results are not adversely affected by intraoral sensor interference.

PMID- 16787903
TI  - Speech effort measurement and stuttering: investigating the chorus reading
      effect.
AB  - PURPOSE: The purpose of this study was to investigate chorus reading's (CR's)
      effect on speech effort during oral reading by adult stuttering speakers and
      control participants. The effect of a speech effort measurement highlighting
      strategy was also investigated. METHOD: Twelve persistent stuttering (PS) adults
      and 12 normally fluent control participants completed 1-min base rate readings
      (BR-nonchorus) and CRs within a BR/CR/BR/CR/BR experimental design. Participants
      self-rated speech effort using a 9-point scale after each reading trial.
      Stuttering frequency, speech rate, and speech naturalness measures were also
      obtained. Instructions highlighting speech effort ratings during BR and CR phases
      were introduced after the first CR. RESULTS: CR improved speech effort ratings
      for the PS group, but the control group showed a reverse trend. Both groups'
      effort ratings were not significantly different during CR phases but were
      significantly poorer than the control group's effort ratings during BR phases.
      The highlighting strategy did not significantly change effort ratings.
      CONCLUSION: The findings show that CR will produce not only stutter-free and
      natural sounding speech but also reliable reductions in speech effort. However,
      these reductions do not reach effort levels equivalent to those achieved by
      normally fluent speakers, thereby conditioning its use as a gold standard of
      achievable normal fluency by PS speakers.

PMID- 16787904
TI  - Proteomic profiling of rat thyroarytenoid muscle.
AB  - PURPOSE: Proteomic methodologies offer promise in elucidating the systemwide
      cellular and molecular processes that characterize normal and diseased
      thyroarytenoid (TA) muscle. This study examined methodological issues central to
      the application of 2-dimensional sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (2D SDS-PAGE) to the study of the TA muscle proteome using a rat
      model. METHOD: 2D SDS-PAGE was performed using 4 chemically skinned rat TA muscle
      samples. Gel images were analyzed and compared. Protein spot detection and
      matching were performed using computational image analysis algorithms only and
      computational image analysis followed by visual inspection and manual error
      correction. A synthetic master gel, constructed to control for uninteresting
      biological variation and technical artifact due to differences in protein loading
      and staining, was evaluated against its constituent gels. RESULTS: Manual error
      correction resulted in a consistent increase in the number of protein spots
      detected (between 5.8% and 40.9%) and matched (from 25.8% to 70.8%) across all
      gels. Sensitivity and specificity of the automatic (computational) spot detection
      procedure, evaluated against the manual correction procedure, were 74.1% and
      97.9%, respectively. Evaluation of protein quantitation parameter values revealed
      statistically significant differences (p < .0001) in optical density, area, and
      volume for matched protein spots across gels. The synthetic master gel
      successfully compensated for these intergel differences. CONCLUSIONS: Valid and
      reliable proteomic data are dependant on well-controlled manageable variability
      and well-defined unmanageable variability. Manual correction of spot detection
      and matching errors and the use of a synthetic master gel appear to be useful
      strategies in addressing these issues. With these issues accounted for, 2D SDS
      PAGE may be applied to quantitative experimental comparisons of normal and
      disease conditions affecting voice, speech, and swallowing function.

PMID- 16787905
TI  - Coherence of medical negligence cases. A game of doctors and purses.

PMID- 16787906
TI  - Outing medical errors: questions of trust and responsibility.

PMID- 16787907
TI  - Assisted dying in France. The evolution of assisted dying in France: a third way?

PMID- 16787908
TI  - Catholic doctrine versus women's rights: the new Italian law on assisted
      reproduction.

PMID- 16787909
TI  - Autonomy rued OK? Al Hamwi v. Johnston and another.

PMID- 16787910
TI  - Taking a neutral stance on the legal protection of the fetus. Vo v. France.

PMID- 16787911
TI  - Psychiatric treatment: in the absence of law? R (on the application of B) v.
      Ashworth Hospital Authority and another.

PMID- 16787912
TI  - The exercise of public health powers in cases of infectious disease: human rights
      implications. Enhorn v. Sweden.

PMID- 16787913
TI  - Interaction of human lactoferrin with cell adhesion molecules through RGD motif
      elucidated by lactoferrin-binding epitopes.
AB  - Lactoferrin (LF) is an iron-binding secretory protein, which is distributed in
      the secondary granules of polynuclear lymphocytes as well as in the milk produced
      by female mammals. Although it has multiple functions, for example antimicrobial,
      immunomodulatory, antiviral, and anti-tumor metastasis activities, the receptors
      responsible for these activities are not fully understood. In this study, the
      binding epitopes for human LF were first isolated from a hexameric random peptide
      library displayed on T7 phage. Interestingly, two of the four isolated peptides
      had a representative cell adhesion motif, Arg-Gly-Asp (RGD), implying that human
      LF interacts with proteins with the RGD motif. We found that human LF bound to
      the RGD-containing human extracellular matrix proteins, fibronectin and
      vitronectin. Furthermore, human LF inhibited cell adhesion to these matrix
      proteins in a concentration-dependent manner but not to the RGD-independent cell
      adhesion molecule like laminin or collagen. These results indicate that a
      function of human LF is to block the various interactions between the cell
      surface and adhesion molecules. This may explain the multifunctionality of LF.

PMID- 16787914
TI  - Human DNA polymerase N (POLN) is a low fidelity enzyme capable of error-free
      bypass of 5S-thymine glycol.
AB  - Human DNA polymerase N (POLN or pol nu) is the most recently discovered nuclear
      DNA polymerase in the human genome. It is an A-family DNA polymerase related to
      Escherichia coli pol I, human POLQ, and Drosophila Mus308. We report the first
      purification of the recombinant enzyme and examination of its biochemical
      properties, as a step toward understanding the functions of POLN. Unusual for an
      A-family DNA polymerase, POLN is a low fidelity enzyme incorporating T opposite
      template G with a frequency of 0.45 and G opposite template T with a frequency of
      0.021. The frequency of misincorporation of T opposite template G is higher than
      any other known DNA polymerase. POLN has a processivity of DNA synthesis (1-100
      nucleotides) similar to the exonuclease-deficient Klenow fragment of E. coli pol
      I, is inhibited by dideoxynucleotides, and resistant to aphidicolin. The strand
      displacement activity of POLN was higher than exonuclease-deficient Klenow
      fragment. Furthermore, POLN can perform translesion synthesis past thymine
      glycol, a common endogenous and radiation-induced product of reactive oxygen
      species damage to DNA. Thymine glycol blocks DNA synthesis by most DNA
      polymerases, but POLN was particularly adept at efficient and accurate
      translesion synthesis past a 5S-thymine glycol.

PMID- 16787915
TI  - Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis
      signaling and iron homeostasis in mouse development.
AB  - Hypoxia-inducible factor-1 (HIF-1) regulates the transcription of genes whose
      products play critical roles in energy metabolism, erythropoiesis, angiogenesis,
      and cell survival. Limited information is available concerning its function in
      mammalian hematopoiesis. Previous studies have demonstrated that homozygosity for
      a targeted null mutation in the Hif1alpha gene, which encodes the hypoxia
      responsive alpha subunit of HIF-1, causes cardiac, vascular, and neural
      malformations resulting in lethality by embryonic day 10.5 (E10.5). This study
      revealed reduced myeloid multilineage and committed erythroid progenitors in HIF
      1alpha-deficient embryos, as well as decreased hemoglobin content in erythroid
      colonies from HIF-1alpha-deficient yolk sacs at E9.5. Dysregulation of
      erythropoietin (Epo) signaling was evident from a significant decrease in mRNA
      levels of Epo receptor (EpoR) in Hif1alpha-/- yolk sac as well as Epo and EpoR
      mRNA in Hif1alpha-/- embryos. The erythropoietic defects in HIF-1alpha-deficient
      erythroid colonies could not be corrected by cytokines, such as vascular
      endothelial growth factor and Epo, but were ameliorated by Fe-SIH, a compound
      delivering iron into cells independently of iron transport proteins. Consistent
      with profound defects in iron homeostasis, Hif1alpha-/- yolk sac and/or embryos
      demonstrated aberrant mRNA levels of hepcidin, Fpn1, Irp1, and frascati. We
      conclude that dysregulated expression of genes encoding Epo, EpoR, and iron
      regulatory proteins contributes to defective erythropoiesis in Hif1alpha-/- yolk
      sacs. These results identify a novel role for HIF-1 in the regulation of iron
      homeostasis and reveal unexpected regulatory differences in Epo/EpoR signaling in
      yolk sac and embryonic erythropoiesis.

PMID- 16787916
TI  - Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1)
      during osteoclastogenesis.
AB  - Osteoclasts differentiate from hematopoietic mononuclear precursor cells under
      the control of both colony stimulating factor-1 (CSF-1, or M-CSF) and receptor
      activator of NF-kappaB ligand (RANKL, or TRANCE, TNFSF11) to carry out bone
      resorption. Using high density gene microarrays, we followed gene expression
      changes in long bone RNA when CSF-1 injections were used to restore osteoclast
      populations in the CSF-1-null toothless (csf1(tl)/csf1(tl)) osteopetrotic rat. We
      found that ovarian cancer G-protein-coupled receptor 1 (OGR1, or GPR68) was
      strongly up-regulated, rising >6-fold in vivo after 2 days of CSF-1 treatments.
      OGR1 is a dual membrane receptor for both protons (extracellular pH) and
      lysolipids. Strong induction of OGR1 mRNA was also observed by microarray, real
      time RT-PCR, and immunoblotting when mouse bone marrow mononuclear cells and RAW
      264.7 pre-osteoclast-like cells were treated with RANKL to induce osteoclast
      differentiation. Anti-OGR1 immunofluorescence showed intense labeling of RANKL
      treated RAW cells. The time course of OGR1 mRNA expression suggests that OGR1
      induction is early but not immediate, peaking 2 days after inducing osteoclast
      differentiation both in vivo and in vitro. Specific inhibition of OGR1 by anti
      OGR1 antibody and by small inhibitory RNA inhibited RANKL-induced differentiation
      of both mouse bone marrow mononuclear cells and RAW cells in vitro, as evidenced
      by a decrease in tartrate-resistant acid phosphatase-positive osteoclasts. Taken
      together, these data indicate that OGR1 is expressed early during
      osteoclastogenesis both in vivo and in vitro and plays a role in osteoclast
      differentiation.

PMID- 16787917
TI  - A minimal promoter for TFIIIC-dependent in vitro transcription of snoRNA and tRNA
      genes by RNA polymerase III.
AB  - The Saccharomyces cerevisiae SNR52 gene is unique among the snoRNA coding genes
      in being transcribed by RNA polymerase III. The primary transcript of SNR52 is a
      250-nucleotide precursor RNA from which a long leader sequence is cleaved to
      generate the mature snR52 RNA. We found that the box A and box B sequence
      elements in the leader region are both required for the in vivo accumulation of
      the snoRNA. As expected box B, but not box A, was absolutely required for stable
      TFIIIC, yet in vitro. Surprisingly, however, the box B was found to be largely
      dispensable for in vitro transcription of SNR52, whereas the box A-mutated
      template effectively recruited TFIIIB; yet it was transcriptionally inactive.
      Even in the complete absence of box B and both upstream TATA-like and T-rich
      elements, the box A still directed efficient, TFIIIC-dependent transcription. Box
      B-independent transcription was also observed for two members of the
      tRNA(Asn)(GTT) gene family, but not for two tRNA(Pro)(AGG) gene copies. Fully
      recombinant TFIIIC supported box B-independent transcription of both SNR52 and
      tRNA(Asn) genes, but only in the presence of TFIIIB reconstituted with a crude
      B'' fraction. Non-TFIIIB component(s) in this fraction were also required for
      transcription of wild-type SNR52. Transcription of the box B-less tRNA(Asn) genes
      was strongly influenced by their 5'-flanking regions, and it was stimulated by
      TBP and Brf1 proteins synergistically. The box A can thus be viewed as a core
      TFIIIC-interacting element that, assisted by upstream TFIIIB-DNA contacts, is
      sufficient to promote class III gene transcription.

PMID- 16787918
TI  - Regulation of murine TGFbeta2 by Pax3 during early embryonic development.
AB  - Previously our laboratory identified TGFbeta2 as a potential downstream target of
      Pax3 by utilizing microarray analysis and promoter data base mining (Mayanil, C.
      S. K., George, D., Freilich, L., Miljan, E. J., Mania-Farnell, B. J., McLone, D.
      G., and Bremer, E. G. (2001) J. Biol. Chem. 276, 49299-49309). Here we report
      that Pax3 directly regulates TGFbeta2 transcription by binding to cis-regulatory
      elements within its promoter. Chromatin immunoprecipitation revealed that Pax3
      bound to the cis-regulatory elements on the TGFbeta2 promoter (GenBanktrade mark
      accession number AF118263). Both TGFbeta2 promoter-luciferase activity
      measurements in transient cotransfection experiments and electromobility shift
      assays supported the idea that Pax3 regulates TGFbeta2 by directly binding to its
      cis-regulatory regions. Additionally, by using a combination of co
      immunoprecipitation and chromatin immunoprecipitation, we show that the TGFbeta2
      cis-regulatory elements between bp 741-940 and bp 1012-1212 bind acetylated Pax3
      and are associated with p300/CBP and histone deacetylases. The cis-regulatory
      elements between bp 741 and 940 in addition to associating with acetylated Pax3
      and HDAC1 also associated with SIRT1. Whole mount in situ hybridization and
      quantitative real time reverse transcription-PCR showed diminished levels of
      TGFbeta2 transcripts in Pax3(-/-) mouse embryos (whose phenotype is characterized
      by neural tube defects) as compared with Pax3(+/+) littermates (embryonic day
      10.0; 30 somite stage), suggesting that Pax3 regulation of TGFbeta2 may play a
      pivotal role during early embryonic development.

PMID- 16787919
TI  - His-384 allotypic variant of factor H associated with age-related macular
      degeneration has different heparin binding properties from the non-disease
      associated form.
AB  - A polymorphism in complement factor H has recently been associated with age
      related macular degeneration (AMD), the leading cause of blindness in the
      elderly. A histidine rather than a tyrosine at residue position 384 in the mature
      protein increases the risk of AMD. Here, using a recombinant construct, we show
      that amino acid 384 is adjacent to a heparin-binding site in CCP7 of factor H and
      demonstrate that the allotypic variants differentially recognize heparin. This
      functional alteration may affect binding of factor H to polyanionic patterns on
      host surfaces, potentially influencing complement activation, immune complex
      clearance, and inflammation in the macula of AMD patients.

PMID- 16787920
TI  - A role for the G12 family of heterotrimeric G proteins in prostate cancer
      invasion.
AB  - Many studies have suggested a role for the members of the G12 family of
      heterotrimeric G proteins (Galpha12 and Galpha13) in oncogenesis and tumor cell
      growth. However, few studies have examined G12 signaling in actual human cancers.
      In this study, we examined the role of G12 signaling in prostate cancer. We found
      that expression of the G12 proteins is significantly elevated in prostate cancer.
      Interestingly, expression of the activated forms of Galpha12 or Galpha13 in the
      PC3 and DU145 prostate cancer cell lines did not promote cancer cell growth.
      Instead, expression of the activated forms of Galpha12 or Galpha13 in these cell
      lines induced cell invasion through the activation of the RhoA family of G
      proteins. Furthermore, inhibition of G12 signaling by expression of the RGS
      domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) in
      the PC3 and DU145 cell lines did not reduce cancer cell growth. However,
      inhibition of G12 signaling with p115-RGS in these cell lines blocked thrombin-
      and thromboxane A2-stimulated cell invasion. These observations identify the G12
      family proteins as important regulators of prostate cancer invasion and suggest
      that these proteins may be targeted to limit invasion- and metastasis-induced
      prostate cancer patient mortality.

PMID- 16787921
TI  - Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic
      receptor and Gi-protein heterotrimer.
AB  - To characterize the mechanism by which heterotrimeric G-proteins interpret the
      signals coming from various neurotransmitters of diverse efficacies (agonists and
      partial agonists) acting on alpha(2A)-adrenergic receptors, we used a fluorescent
      resonance energy transfer-based approach to study the effects of these partial
      agonists on the activation process of both the alpha(2A)-adrenergic receptor and
      its cognate G(i)-protein. We show that ligands of different efficacies switch the
      receptor into distinct conformational states, which in turn set the speed and
      extent of the G(i)-protein signaling. Thus, in cells the efficacy by which a
      receptor responds to diverse ligands is caused by the ability of the G-protein to
      differentiate between distinct receptor conformations. The data provide a new key
      characteristic underlying the mechanism of partial agonism at G-protein-coupled
      receptors.

PMID- 16787922
TI  - Transcription of human zinc finger ZNF268 gene requires an intragenic promoter
      element.
AB  - Human ZNF268 gene is a typical Kruppel-associated box/C2H2 zinc finger gene whose
      homolog has been found only in higher mammals and not in lower mammals such as
      mouse. Its expression profiles have suggested that it plays a role in the
      differentiation of blood cells during early human embryonic development and the
      pathogenesis of leukemia. To gain additional insight into the molecular
      mechanisms controlling the expression of the ZNF268 gene and to provide the
      necessary tools for further genetic studies of leukemia, we have mapped the 5'
      end of the human ZNF268 mRNA by reverse transcription-PCR and primer extension
      assays. We then cloned the 5'-flanking genomic DNA containing the putative ZNF268
      gene promoter and analyzed its function in several different human and mouse
      tissue culture cell lines. Interestingly, our studies show that the ZNF268 gene
      lacks a typical eukaryotic promoter that is present upstream of the transcription
      start site and directs a basal level of transcription. Instead, the functional
      promoter requires an essential element that is located within the first exon of
      the gene. Deletion and mutational analysis reveals the requirement for a cAMP
      response-element-binding protein (CREB)-binding site within this element for
      promoter function. Gel mobility shift and chromatin immunoprecipitation assays
      confirm that CREB-2 binds to the site in vitro and in vivo. Furthermore,
      overexpression of CREB-2 enhances the promoter activity. These results
      demonstrate that the human ZNF268 gene promoter is atypical and requires an
      intragenic element located within the first exon that mediates the effect of CREB
      for its activity.

PMID- 16787923
TI  - Coupling of agonist binding to effector domain activation in metabotropic
      glutamate-like receptors.
AB  - Many membrane receptors are made of a ligand binding domain and an effector
      domain mediating intracellular signaling. This is the case for the metabotropic
      glutamate-like G-protein-coupled receptors. How ligand binding leads to the
      active conformation of the effector domain in such receptors is largely unknown.
      Here, we used an evolutionary trace analysis and mutagenesis to identify critical
      residues involved in the allosteric coupling between the Venus flytrap ligand
      binding domain (VFT) and the heptahelical G-protein activating domain of the
      metabotropic glutamate-like receptors. We have shown that a conserved interdomain
      disulfide bridge is required for this allosteric interaction. Taking into account
      that these receptors are homodimers, this finding provides important new
      information explaining how the different conformations of the dimer of VFT lead
      to different signaling of such dimeric receptors.

PMID- 16787924
TI  - Reactive oxygen species mediate the potentiating effects of ATP on GABAergic
      synaptic transmission in the immature hippocampus.
AB  - Reactive oxygen species (ROS) constitute important signaling molecules in the
      central nervous system. They regulate a number of different functions both under
      physiological conditions and under pathological conditions. Here we tested the
      hypothesis that in the immature hippocampus ATP, the most diffuse
      neurotransmitter in the brain, modulates synaptic transmission via ROS. We show
      that ATP, acting on metabotropic P2Y1 receptors, increased the frequency of
      GABA(A)-mediated spontaneous postsynaptic currents (SPSCs) in CA3 principal
      cells, an effect that was prevented by the antioxidant N-acetyl-cysteine or by
      catalase, an enzyme that breaks down H2O2. The effect of ATP on SPSCs was
      mimicked by H2O2 or by the pro-oxidant, Fe2+, which, through the Fentol reaction,
      catalyzes the conversion of H2O2 into highly reactive hydroxyl radicals. MRS
      2179, a P2Y1 receptor antagonist, removed the facilitatory action of Fe2+ on
      SPSCs, suggesting that endogenous ATP acting on P2Y1 receptors is involved in
      Fe2+-induced modulation of synaptic transmission. Imaging ROS with the H2O2
      sensitive dye DCF revealed that ATP induces generation of peroxide in astrocytes
      via activation of P2Y1 receptors coupled to intracellular calcium rise. Neither N
      acetyl-cysteine nor catalase prevented Ca2+ transients induced by ATP in
      astrocytes. Since a single hippocampal astrocyte can contact many neurons, ATP
      induced ROS signaling may control thousands of synapses. This may be crucial for
      information processing in the immature brain when GABAergic activity is essential
      for the proper wiring of the hippocampal network.

PMID- 16787925
TI  - The adaptor protein Gab1 couples the stimulation of vascular endothelial growth
      factor receptor-2 to the activation of phosphoinositide 3-kinase.
AB  - Phosphoinositide 3-kinase (PI3K) mediates essential functions of vascular
      endothelial growth factor (VEGF), including the stimulation of endothelial cell
      proliferation and migration. Nevertheless, the mechanisms coupling the receptor
      VEGFR-2 to PI3K remain obscure. We observed that the Grb2-bound adapter Gab1 is
      tyrosine-phosphorylated and relocated to membrane fractions upon VEGF stimulation
      of endothelial cells. We could detect the PI3K regulatory subunit p85 in
      immunoprecipitates of endogenous Gab1, and vice versa, and measure a Gab1
      associated lipid kinase activity upon VEGF stimulation. Furthermore, transfection
      of the Gab1-YF3 mutant lacking all p85-binding sites strongly repressed PI3K
      activation measured in vitro. Moreover, Gab1-YF3 severely decreased the cellular
      amount of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generated in
      response to VEGF. Furthermore, adenoviral expression of Gab1-YF3 suppressed both
      Akt phosphorylation and recovery of wounded human umbilical vein endothelial cell
      monolayers, a VEGF-dependent process involving cell migration and proliferation
      under PI3K control. Transfection of other Gab1 mutants, lacking Grb2-binding
      sites or the pleckstrin homology (PH) domain, also prevented Akt activation,
      further demonstrating Gab1 involvement in PI3K activation. These mutants were
      also used to show that interactions with both Grb2 and PtdIns(3,4,5)P3 mediate
      Gab1 recruitment by VEGFR-2. Importantly, Gab1 mobilization was impaired by (i)
      PI3K inhibitors, (ii) deletion of Gab1 PH domain, (iii) PTEN (phosphatase and
      tensin homolog deleted on chromosome 10) overexpression to repress
      PtdIns(3,4,5)P3 production, and (iv) overexpression of a competitor PH domain for
      PtdIns(3,4,5)P3 binding, which altogether demonstrated that PI3K is also an
      upstream regulator of Gab1. Gab1 thus appears as a primary actor in coupling
      VEGFR-2 to PI3K/Akt, recruited through an amplification loop involving
      PtdIns(3,4,5)P3 and its PH domain.

PMID- 16787926
TI  - Correction of pulmonary abnormalities in Sftpd-/- mice requires the collagenous
      domain of surfactant protein D.
AB  - Surfactant protein D (SP-D) is a member of the collectin family of innate defense
      proteins. Members of this family share four distinct structural domains: an N
      terminal cross-linking domain, a collagenous domain, a neck region, and a
      carbohydrate recognition domain. In this study, the function of the collagenous
      domain was evaluated by expressing a SP-D collagen deletion mutant protein
      (rSftpdCDM) in wild type and SP-D null mice (Sftpd(-/-)). rSftpdCDM formed
      disulfide-linked trimers that further oligomerized into higher order structures.
      The mutant protein effectively bound carbohydrate and aggregated bacteria in
      vitro. Whereas rSftpdCDM did not disrupt pulmonary morphology or surfactant
      phospholipid levels in wild type mice, the mutant protein failed to rescue the
      emphysema or enlarged foamy macrophages that are characteristic of Sftpd(-/-)
      mice. Moreover, rSftpdCDM partitioned with small aggregate surfactant in a manner
      similar to SP-D, but rSftpdCDM did not correct the abnormal surfactant
      ultrastructure or phospholipid levels observed in Sftpd(-/-) mice. In contrast,
      rSftpdCDM completely corrected viral clearance and the abnormal inflammatory
      response that occurs following pulmonary influenza A challenge in Sftpd(-/-)
      mice. Our findings indicate that the collagen domain of SP-D is not required for
      assembly of disulfide-stabilized oligomers or the innate immune response to viral
      pathogens. The collagen domain of SP-D is required for the regulation of
      pulmonary macrophage activation, airspace remodeling, and surfactant lipid
      homeostasis.

PMID- 16787927
TI  - Differential stability of thymidylate synthase 3'-untranslated region polymorphic
      variants regulated by AUF1.
AB  - A 6-nucleotide insertion (I)/deletion (D) polymorphism in the 3'-untranslated
      region of the thymidylate synthase gene was shown to influence mRNA stability,
      but the molecular basis of this effect has not been elucidated. Here, studies of
      both endogenous and ectopically expressed thymidylate synthase alleles revealed
      that the mRNA-binding, decay-promoting protein AUF1 has higher affinity for
      allele D mRNA. AUF1 overexpression preferentially suppressed D allele mRNA
      levels, whereas AUF1 silencing selectively elevated D allele mRNA levels. Our
      results illustrate the functional consequences of ribonucleoprotein associations
      involving a polymorphic RNA sequence and uncover a novel mechanism of action for
      non-coding RNA polymorphisms.

PMID- 16787928
TI  - RNA silencing of mitochondrial m-Nfs1 reduces Fe-S enzyme activity both in
      mitochondria and cytosol of mammalian cells.
AB  - In prokaryotes and yeast, the general mechanism of biogenesis of iron-sulfur (Fe
      S) clusters involves activities of several proteins among which IscS and Nfs1p
      provide, through cysteine desulfuration, elemental sulfide for Fe-S core
      formation. Although these proteins have been well characterized, the role of
      their mammalian homolog in Fe-S cluster biogenesis has never been evaluated. We
      report here the first functional study that implicates the putative cysteine
      desulfurase m-Nfs1 in the biogenesis of both mitochondrial and cytosolic
      mammalian Fe-S proteins. Depletion of m-Nfs1 in cultured fibroblasts through
      small interfering RNA-based gene silencing significantly inhibited the activities
      of mitochondrial NADH-ubiquinone oxidoreductase (complex I) and succinate
      ubiquinone oxidoreductase (complex II) of the respiratory chain, as well as
      aconitase of the Krebs cycle, with no alteration in their protein levels.
      Activity of cytosolic xanthine oxidase, which holds a [2Fe-2S] cluster, was also
      specifically reduced, and iron-regulatory protein-1 was converted from its [4Fe
      4S] aconitase form to its apo- or RNA-binding form. Reduction of Fe-S enzyme
      activities occurred earlier and more markedly in the cytosol than in
      mitochondria, suggesting that there is a mechanism that primarily dedicates m
      Nfs1 to the biogenesis of mitochondrial Fe-S clusters in order to maintain cell
      survival. Finally, depletion of m-Nfs1, which conferred on apo-IRP-1 a high
      affinity for ferritin mRNA, was associated with the down-regulation of the iron
      storage protein ferritin.

PMID- 16787929
TI  - Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact
      plaques in situ.
AB  - The pathological hallmark of Alzheimer disease is the senile plaque principally
      composed of tightly aggregated amyloid-beta fibrils (fAbeta), which are thought
      to be resistant to degradation and clearance. In this study, we explored whether
      proteases capable of degrading soluble Abeta (sAbeta) could degrade fAbeta as
      well. We demonstrate that matrix metalloproteinase-9 (MMP-9) can degrade fAbeta
      and that this ability is not shared by other sAbeta-degrading enzymes examined,
      including endothelin-converting enzyme, insulin-degrading enzyme, and neprilysin.
      fAbeta was decreased in samples incubated with MMP-9 compared with other
      proteases, assessed using thioflavin-T. Furthermore, fAbeta breakdown with MMP-9
      but not with other proteases was demonstrated by transmission electron
      microscopy. Proteolytic digests of purified fAbeta were analyzed with matrix
      assisted laser desorption ionization time-of-flight mass spectrometry to identify
      sites of Abeta that are cleaved during its degradation. Only MMP-9 digests
      contained fragments (Abeta(1-20) and Abeta(1-30)) from fAbeta(1-42) substrate;
      the corresponding cleavage sites are thought to be important for beta-pleated
      sheet formation. To determine whether MMP-9 can degrade plaques formed in vivo,
      fresh brain slices from aged APP/PS1 mice were incubated with proteases. MMP-9
      digestion resulted in a decrease in thioflavin-S (ThS) staining. Consistent with
      a role for endogenous MMP-9 in this process in vivo, MMP-9 immunoreactivity was
      detected in astrocytes surrounding amyloid plaques in the brains of aged APP/PS1
      and APPsw mice, and increased MMP activity was selectively observed in compact
      ThS-positive plaques. These findings suggest that MMP-9 can degrade fAbeta and
      may contribute to ongoing clearance of plaques from amyloid-laden brains.

PMID- 16787930
TI  - Regulation of glutamine and glutamate metabolism by GlnR and GlnA in
      Streptococcus pneumoniae.
AB  - Several genes involved in nitrogen metabolism are known to contribute to the
      virulence of pathogenic bacteria. Here, we studied the function of the nitrogen
      regulatory protein GlnR in the Gram-positive human pathogen Streptococcus
      pneumoniae. We demonstrate that GlnR mediates transcriptional repression of genes
      involved in glutamine synthesis and uptake (glnA and glnPQ), glutamate synthesis
      (gdhA), and the gene encoding the pentose phosphate pathway enzyme Zwf, which
      forms an operon with glnPQ. Moreover, the expression of gdhA is also repressed by
      the pleiotropic regulator CodY. The GlnR-dependent regulation occurs through a
      conserved operator sequence and is responsive to the concentration of glutamate,
      glutamine, and ammonium in the growth medium. By means of in vitro binding
      studies and transcriptional analyses, we show that the regulatory function of
      GlnR is dependent on GlnA. Mutants of glnA and glnP displayed significantly
      reduced adhesion to Detroit 562 human pharyngeal epithelial cells, suggesting a
      role for these genes in the colonization of the host by S. pneumoniae. Thus, our
      results provide a thorough insight into the regulation of glutamine and glutamate
      metabolism of S. pneumoniae mediated by both GlnR and GlnA.

PMID- 16787931
TI  - Efficacy and plasma levels of ropivacaine for children: controlled regional
      analgesia following lower limb surgery.
AB  - BACKGROUND: Continuous regional analgesia (CRA) is considered a safe and
      efficacious technique for postoperative pain relief in children after lower limb
      surgery. We recently evaluated the feasibility of patient-controlled regional
      analgesia (PCRA) in a similar acute pain situation and we concluded that PCRA
      might be advantageous over CRA in terms of lower costs, risk of systemic toxicity
      while producing similarly adequate analgesia. We therefore prospectively compared
      both techniques in the paediatric population. METHODS: In total, 30 children
      undergoing lower limb orthopaedic surgery were randomized to receive PCRA or CRA
      with ropivacaine 0.2%. Visual analogue scale scores, rescue analgesia, overall
      satisfaction, motor blockade and plasma ropivacaine concentrations were recorded
      for 48 h. RESULTS: Adequate analgesia was achieved with both techniques. No
      significant difference was noted for rescue analgesia, overall satisfaction and
      motor blockade. In contrast, children in the PCRA group received significantly
      less local anaesthetics than those in the CRA group. In addition, total plasma
      concentrations of ropivacaine were significantly reduced in the PCRA group as
      compared with the CRA group during the 48 h postoperative period. CONCLUSIONS:
      Both techniques are efficacious and satisfactory. However, PCRA with ropivacaine
      0.2% can provide adequate postoperative analgesia for paediatric orthopaedic
      procedures with smaller doses of ropivacaine than CRA.

PMID- 16787932
TI  - How nonprofits matter in American medicine, and what to do about it.
AB  - Skeptics question nonprofit health care on the grounds that nonprofits fail to
      distinguish themselves from their for-profit counterparts and do not reliably
      provide community benefits commensurate with their tax subsidies. Drawing on the
      most recent and comprehensive evidence, we assess these charges, judging them to
      be either wrong or incomplete. Although conventional critiques are therefore
      unconvincing, there are nonetheless important challenges facing the nonprofit
      sector in American medicine. To address these, we propose reformulating ownership
      related policies to define both the appropriate forms of community benefit and
      the appropriate mix of ownership in terms of local markets and communities.

PMID- 16787933
TI  - Nonprofit ownership, private property, and public accountability.
AB  - Mark Schlesinger and Brad Gray have summarized research comparing nonprofit and
      for-profit health care in a remarkably useful form. Their paper effectively
      demonstrates how nonprofit and for-profit health care differ. However, their
      proposal for community control over nonprofit health care organizations in
      exchange for tax exemption, like many current proposals requiring nonprofit
      hospitals to provide free care for indigent patients, risks undermining the
      purpose of the nonprofit organizations and the care they provide. These trade
      offs are significant yet have not been acknowledged in policy debate.

PMID- 16787934
TI  - Subsidizing health care providers through the tax code: status or conduct?
AB  - The merits of tax exemption for nonprofit health care providers have been hotly
      debated for decades. Mark Schlesinger and Brad Gray provide a useful,
      dispassionate meta-analysis of past research; they conclude that there are real
      differences in the performance of nonprofit and for-profit hospitals and nursing
      homes, although they vary along several key dimensions. Unfortunately, their
      findings offer no insight on whether these differences are large enough to
      justify a sizable subsidy and whether it makes more sense to use an
      undifferentiated subsidy tied to status (current practice), or a graduated
      subsidy tied to quantifiable and objective measures of performance.

PMID- 16787935
TI  - Tax preferences for nonprofits: from per se exemption to pay-for-performance.
AB  - Defenders of tax preferences for nonprofit hospitals and health plans, including
      Mark Schlesinger and Brad Gray, contend that nonprofits deserve government
      support because they provide greater "community benefit" than their for-profit
      counterparts. This argument is unconvincing. There is some evidence that
      nonprofits deliver marginally more "community benefit" but no evidence that tax
      exemption is the cause. Absent proof that tax expenditures, including exemption,
      "buy" social benefits that are worth the cost to taxpayers, these expenditures
      are unjustified. The better course would be to pay nonprofits for performance, by
      tying tax benefits to accomplishments (beyond current achievements) in health
      promotion, quality, and care for the needy.

PMID- 16787936
TI  - Two stages of light-dependent TRPL-channel translocation in Drosophila
      photoreceptors.
AB  - Transient receptor potential (TRP) channels across species are expressed in
      sensory receptor cells, and often localized to specialized subcellular sites. In
      Drosophila photoreceptors, TRP-like (TRPL) channels are localized to the
      signaling compartment, the rhabdomere, in the dark, and undergo light-induced
      translocation into the cell body as a mechanism for long-term light-adaptation.
      We show that translocation of TRPL channels occurs in two distinct stages, first
      to the neighboring stalk membrane then to the basolateral membrane. In the first
      stage, light-induced translocation occurs within 5 minutes, whereas the second
      stage takes over 6 hours. The exclusive apical localization of TRPL channels in
      the first stage of translocation suggests that channels are released from the
      rhabdomere and diffuse laterally through the membrane into the adjoining stalk
      membrane. In the second stage, TRPL channels are localized in the basolateral
      membrane, implicating a different transport mechanism. Genetic analyses suggest
      that activation of the other light-activated TRP channel and eye-protein-kinase C
      (eye-PKC) are both required for the second stage of TRPL translocation in R1 to
      R6 photoreceptor cells, whereas only phospholipase C (PLC) is required for the
      first stage. Finally, we show that arrestin2 is required for the rhabdomeric
      localization and stability of TRPL channels.

PMID- 16787937
TI  - Atg9 sorting from mitochondria is impaired in early secretion and VFT-complex
      mutants in Saccharomyces cerevisiae.
AB  - In eukaryotic cells, the turnover of long-lived proteins and large cytoplasmic
      structures is mediated by autophagy. Components that have to be eliminated are
      sequestered into double-membrane vesicles called autophagosomes and delivered
      into the lysosome or vacuole where they are destroyed by resident hydrolases. The
      integral membrane protein Atg9 is essential for both autophagy and the cytoplasm
      to-vacuole targeting pathway, a selective biosynthetic process in Saccharomyces
      cerevisiae that is mechanistically and morphologically similar to autophagy. Atg9
      cycles between the pre-autophagosomal structure, the putative site of double
      membrane vesicle biogenesis and mitochondria. To understand the function of Atg9,
      and also its trafficking mode between these two locations, we identified mutants
      that affect specific Atg9 transport steps. We recently reported that five Atg
      proteins and phosphatidylinositol-3-phosphate regulate Atg9 recycling from the
      pre-autophagosomal structure. Here, we describe a different category of mutants
      that blocks Atg9 sorting from mitochondria. All mutants have been previously
      shown to be required for the normal progression of both the Cvt pathway and
      autophagy, but their precise role in these transport routes was unknown.

PMID- 16787938
TI  - Systematic analysis of myotubularins: heteromeric interactions, subcellular
      localisation and endosome related functions.
AB  - The myotubularins are a large family of lipid phosphatases with specificity
      towards PtdIns3P and PtdIns(3,5)P(2). Each of the 14 family members bears a
      signature phosphatase domain, which is inactive in six cases due to amino acid
      changes at the catalytic site. Fragmentary data have indicated heteromeric
      interactions between myotubularins, which have hitherto paired an active family
      member with an inactive one. In this study we have conducted a largescale
      analysis of potential associations within the human myotubularin family, through
      directed two-hybrid screening and immunoprecipitation of epitope-tagged proteins.
      We have confirmed all previously reported combinations and identified novel
      heteromeric interactions: MTMR8 with MTMR9, and MTMR3 with MTMR4, the first such
      combination of enzymatically active MTMs. We also report the capacity of several
      family members to self-associate, including MTMR3 and MTMR4. Subcellular
      localisation studies reveal a unique distribution of MTMR4 to endosomal
      structures, the major site of substrate lipid accumulation. All active MTMs we
      have tested (MTM1, MTMR2-MTMR4) reduce endosomal PtdIns3P levels upon
      overexpression. Despite this, only MTMR4 exerts any effect on EGF receptor
      trafficking and degradation, which is more pronounced with a phosphatase inactive
      form of MTMR4 and requires an intact FYVE domain.

PMID- 16787939
TI  - Tomosyn-1 is involved in a post-docking event required for pancreatic beta-cell
      exocytosis.
AB  - Although the assembly of a ternary complex between the SNARE proteins syntaxin-1,
      SNAP25 and VAMP2 is known to be crucial for insulin exocytosis, the mechanisms
      controlling this key event are poorly understood. We found that pancreatic beta
      cells express different isoforms of tomosyn-1, a syntaxin-1-binding protein
      possessing a SNARE-like motif. Using atomic force microscopy we show that the
      SNARE-like domain of tomosyn-1 can form a complex with syntaxin-1 and SNAP25 but
      displays binding forces that are weaker than those observed for VAMP2 (237+/-13
      versus 279+/-3 pN). In pancreatic beta-cells tomosyn-1 was found to be
      concentrated in cellular compartments enriched in insulin-containing secretory
      granules. Silencing of tomosyn-1 in the rat beta-cell line INS-1E by RNA
      interference did not affect the number of secretory granules docked at the plasma
      membrane but led to a reduction in stimulus-induced exocytosis. Replacement of
      endogenous tomosyn-1 with mouse tomosyn-1, which differs in the nucleotide
      sequence from its rat homologue and escapes silencing, restored a normal
      secretory rate. Taken together, our data suggest that tomosyn-1 is involved in a
      post-docking event that prepares secretory granules for fusion and is necessary
      to sustain exocytosis of pancreatic beta-cells in response to insulin
      secretagogues.

PMID- 16787940
TI  - Ligands on the string: single-molecule AFM studies on the interaction of
      antibodies and substrates with the Na+-glucose co-transporter SGLT1 in living
      cells.
AB  - Atomic force microscopy (AFM) was used to probe topology, conformational changes
      and initial substrate-carrier interactions of Na+-glucose co-transporter (SGLT1)
      in living cells on a single-molecule level. By scanning SGLT1-transfected Chinese
      hamster ovary (CHO) cells with AFM tips carrying an epitope-specific antibody
      directed against the extramembranous C-terminal loop 13, significant recognition
      events could be detected. Specificity was confirmed by the absence of events in
      nontransfected CHO cells and by the use of free antigen and free antibody
      superfusion. Thus, contrary to computer predictions on SGLT1 topology, loop 13
      seems to be part of the extracellular surface of the transporter. Binding
      probability of the antibody decreased upon addition of phlorizin, a specific
      inhibitor of SGLT1, suggesting a considerable conformational change of loop 13
      when the inhibitor occludes the sugar translocation pathway. Using an AFM tip
      carrying 1-thio-D-glucose, direct evidence could be obtained that in the presence
      of Na+ a sugar-binding site appears on the transporter surface. The binding site
      accepts the sugar residue of the glucoside phlorizin, free D-glucose, and D
      galactose, but not free L-glucose and probably represents the first of several
      selectivity filters of the transporter. This work demonstrates the potential of
      AFM to study the presence and dynamics of plasma membrane transporters in intact
      cells on the single molecule level.

PMID- 16787941
TI  - The Schizosaccharomyces pombe septation initiation network (SIN) is required for
      spore formation in meiosis.
AB  - When nutrients are abundant, S. pombe cells grow as rods, dividing by fission
      after formation of a medially placed cell wall or division septum. Septum
      formation is triggered by a group of proteins, called the septation initiation
      network or SIN, that trigger contraction of the acto-myosin contractile ring at
      the end of mitosis. Ectopic activation of the SIN can uncouple septum formation
      from other cell-cycle events, whereas loss of SIN signalling gives rise to
      multinucleated cells due to the failure of cytokinesis. When starved, S. pombe
      cells of opposite mating types fuse to form a diploid zygote that undergoes
      meiosis and produces four spores. No septa or contractile rings are formed during
      meiosis. In this study, we have investigated the role of the SIN in meiosis. Our
      data show that, whereas the meiotic divisions appear normal, SIN mutants cannot
      form spores. Forespore membrane formation is initiated, but the nuclei are not
      encapsulated properly. The SIN proteins localise to the spindle pole body in
      meiosis. The protein kinases Sid1p and Cdc7p do not associate with the spindle
      pole body until meiosis II, when forespore membrane deposition begins. These data
      indicate a role for the SIN in regulating spore formation during meiosis.

PMID- 16787942
TI  - Ablation of the single dynamin of T. brucei blocks mitochondrial fission and
      endocytosis and leads to a precise cytokinesis arrest.
AB  - Mitochondrial fission is mediated by dynamin-like proteins (DLPs). Trypanosoma
      brucei contains a single DLP, which is the only member of the dynamin
      superfamily. We have previously shown that expression of the human proapoptotic
      Bax in T. brucei induces extensive mitochondrial fragmentation. Here we report
      that Baxinduced mitochondrial fission is abolished in cell lines lacking
      functional DLP suggesting that the protein is also required for mitochondrial
      division during the cell cycle. Furthermore, DLP-ablated cells are deficient for
      endocytosis and as a consequence accumulate enlarged flagellar pockets. Thus,
      besides its expected role in mitochondrial fission the trypanosomal DLP is
      required for endocytosis, a function thought to be restricted to classical
      dynamins. In agreement with its dual function, the DLP localizes to both the
      mitochondrion and the flagellar pocket, the site where endocytosis occurs.
      Unexpectedly, ablation of DLP also causes an arrest of cytokinesis. The fact that
      no multinucleation is observed in the arrested cells argues for a precise cell
      cycle block. Furthermore, analysis of a clathrin-knockdown cell line suggests
      that the cytokinesis arrest is not due to the endocytosis defect. Thus, our
      results support a working model in which mitochondrial fission triggers a
      checkpoint for cytokinesis.

PMID- 16787943
TI  - Two distinct pools of Src family tyrosine kinases regulate PDGF-induced DNA
      synthesis and actin dorsal ruffles.
AB  - The mechanism by which the Src family of protein-tyrosine kinases (SFKs) regulate
      mitogenesis and morphological changes induced by platelet-derived growth factor
      (PDGF) is not well known. The cholesterol-enriched membrane microdomains,
      caveolae, regulate PDGF receptor signalling in fibroblasts and we examined their
      role in SFK functions. Here we show that caveolae disruption by membrane
      cholesterol depletion or expression of the dominant-negative caveolin-3 DGV
      mutant impaired Src mitogenic signalling including kinase activation, Myc gene
      induction and DNA synthesis. The impact of caveolae on SFK function was
      underscored by the capacity of Myc to overcome mitogenic inhibition as a result
      of caveolae disruption. Using biochemical fractionation we show that caveolae
      enriched subcellular membranes regulate the formation of PDGF-receptor-SFK
      complexes. An additional pool of PDGF-activated SFKs that was insensitive to
      membrane cholesterol depletion was characterised in non-caveolae fractions. SFK
      activation outside caveolae was linked to the capacity of PDGF to induce F-actin
      rearrangements leading to dorsal ruffle formation. Inhibition of phospholipase C
      gamma (PLCgamma), sphingosine kinase and heterotrimeric Gi proteins implicates a
      PLC gamma-sphingosine-1-phosphate-Gi pathway for PDGF-induced SFK activation
      outside caveolae and actin assembly. In addition, the cytoplasmic tyrosine kinase
      Abl was identified as an important effector of this signalling cascade. We
      conclude that PDGF may stimulate two spatially distinct pools of SFKs leading to
      two different biological outcomes: DNA synthesis and dorsal ruffle formation.

PMID- 16787944
TI  - The connection between splicing and cancer.
AB  - Alternative splicing is a crucial mechanism for generating protein diversity.
      Different splice variants of a given protein can display different and even
      antagonistic biological functions. Therefore, appropriate control of their
      synthesis is required to assure the complex orchestration of cellular processes
      within multicellular organisms. Mutations in cis-acting splicing elements or
      changes in the activity of constitutive or alternative splicing could have a
      profound regulatory proteins that compromise the accuracy of either impact on
      human pathogenesis, in particular in tumor development and progression. Mutations
      in splicing elements, for example, have been found in genes such as LKB1, KIT,
      CDH17, KLF6 and BRCA1, and changes in trans-acting regulators can affect the
      expression of genes such as Ron, RAC1 and CD44.

PMID- 16787945
TI  - betaPIX controls cell motility and neurite extension by regulating the
      distribution of GIT1.
AB  - Cell motility entails the reorganization of the cytoskeleton and membrane
      trafficking for effective protrusion. GIT1/p95-APP1 is a member of a family of
      GTPase-activating proteins for ARF GTPases that affect endocytosis, adhesion and
      migration. GIT1 associates with paxillin and a complex including the Rac/Cdc42
      exchanging factors PIX/Cool and the kinase PAK. In this study, we show that
      overexpression of betaPIX induces the accumulation of endogenous and
      overexpressed GIT1 at large structures similar to those induced by an ArfGAP
      defective mutant of GIT1 (p95-C2). Immunohistochemical analysis and
      immunoelectron microscopy reveal that these structures include the endogenous
      transferrin receptor. Time-lapse analysis during motogenic stimuli shows that the
      formation and perinuclear accumulation of the p95-C2-positive structures is
      paralleled by inhibition of lamellipodium formation and cell retraction. Both
      dimerization and a functional SH3 domain of betaPIX are required for the
      accumulation of GIT1 in fibroblasts, which is prevented by the monomeric PIX-PG
      DeltaLZ. This mutant also prevents the formation of endocytic aggregates and
      inhibition of neurite outgrowth in retinal neurons expressing p95-C2. Our results
      indicate that betaPIX is an important regulator of the subcellular distribution
      of GIT1, and suggest that alteration in the level of expression of the complex
      affects the endocytic compartment and cell motility.

PMID- 16787946
TI  - Modulation of the PI 3-kinase-Akt signalling pathway by IGF-I and PTEN regulates
      the differentiation of neural stem/precursor cells.
AB  - Neural stem cells depend on insulin-like growth factor I (IGF-I) for
      differentiation. We analysed how activation and inhibition of the PI 3-kinase-Akt
      signalling affects the number and differentiation of mouse olfactory bulb stem
      cells (OBSCs). Stimulation of the pathway with insulin and/or IGF-I, led to an
      increase in Akt phosphorylated on residues Ser473 and Thr308 (P-Akt(Ser473) and P
      Akt(Thr308), respectively) in proliferating OBSCs, and in differentiating cells.
      Conversely, P-Akt(Ser473) levels decreased by 50% in the OB of embryonic day 16.5
      18.5 IGF-I knockout mouse embryos. Overexpression of PTEN, a negative regulator
      of the PI 3-kinase pathway, caused a reduction in the basal levels of P
      Akt(Ser473) and P-Akt(Thr308) and a minor reduction in IGF-I-stimulated P
      Akt(Ser473). Although PTEN overexpression decreased the proportion of neurons and
      astrocytes in the absence of insulin/IGF-I, it did not alter the proliferation or
      survival of OBSCs. Accordingly, overexpression of a catalytically inactive PTEN
      mutant promoted OBSCs differentiation. Inhibition of PI 3-kinase by LY294002
      produced strong and moderate reductions in IGF-I-stimulated P-Akt(Ser473) and P
      Akt(Thr308), respectively. Consequently, LY294002 reduced the proliferation of
      OBSCs and the number of neurons and astrocytes, and also augmented cell death.
      These findings indicate that OBSC differentiation is more sensitive to lower
      basal levels of P-Akt than proliferation or death. By regulating P-Akt levels in
      opposite ways, IGF-I and PTEN contribute to the fine control of neurogenesis in
      the olfactory bulb.

PMID- 16787947
TI  - Heterotrimeric G proteins form stable complexes with adenylyl cyclase and Kir3.1
      channels in living cells.
AB  - Bioluminescence resonance energy transfer (BRET) and co-immunoprecipitation
      experiments revealed that heterotrimeric G proteins and their effectors were
      found in stable complexes that persisted during signal transduction. Adenylyl
      cyclase, Kir3.1 channel subunits and several G-protein subunits (Galpha(s),
      Galpha(i), Gbeta(1) and Ggamma(2)) were tagged with luciferase (RLuc) or GFP, or
      the complementary fragments of YFP (specifically Gbeta(1)-YFP(1-158) and
      Ggamma(2)-YFP(159-238), which heterodimerize to produce fluorescent YFP
      Gbeta(1)gamma(2)). BRET was observed between adenylyl-cyclase-RLuc or Kir3.1-RLuc
      and GFP-Ggamma(2), GFP-Gbeta(1) or YFP-Gbeta(1)gamma(2). Galpha subunits were
      also stably associated with both effectors regardless of whether or not signal
      transduction was initiated by a receptor agonist. Although BRET between effectors
      and Gbetagamma was increased by receptor stimulation, our data indicate that
      these changes are likely to be conformational in nature. Furthermore, receptor
      sensitive G-protein-effector complexes could be detected before being transported
      to the plasma membrane, providing the first direct evidence for an intracellular
      site of assembly.

PMID- 16787948
TI  - Interplay of PIWI/Argonaute protein MIWI and kinesin KIF17b in chromatoid bodies
      of male germ cells.
AB  - Chromatoid bodies are thought to act as male-germ-cell-specific platforms for the
      storing and processing of haploid transcripts. The molecular mechanisms governing
      the formation and function of these germ-cell-specific structures have remained
      elusive. In this study, we show that the kinesin motor protein KIF17b, which is
      involved in the nucleocytoplasmic transport of RNA and of a transcriptional
      coactivator, localizes in chromatoid bodies. The chromatoid body moves actively
      and non-randomly in the cytoplasm of round spermatids, making frequent contacts
      with the nuclear envelope. The localization of KIF17b thereby offers a potential
      mechanism for microtubule-dependent mobility of chromatoid bodies, as well as for
      the transport of the specific components in and out of the chromatoid body.
      Interestingly, we demonstrate that KIF17b physically interacts with a testis
      specific member of the PIWI/Argonaute family, MIWI, a component of chromatoid
      bodies implicated in RNA metabolism. A functional interplay between KIF17b and
      MIWI might be needed for the loading of haploid RNAs in the chromatoid body.
      Importantly, chromatoid bodies from round spermatids of miwi-null mice are not
      fully compacted and remain as a diffuse chromatoid material, revealing the
      essential role played by MIWI in the formation of chromatoid bodies. These
      results shed new light on the function of chromatoid bodies in the post
      transcriptional regulation of gene expression in haploid germ cells.

PMID- 16787949
TI  - Active and passive displacement of transmembrane domains both occur during opsin
      biogenesis at the Sec61 translocon.
AB  - We used a site-specific crosslinking approach to study the membrane integration
      of the polytopic protein opsin at the endoplasmic reticulum. We show that
      transmembrane domain 1 occupies two distinct Sec61-based environments during its
      integration. However, transmembrane domains 2 and 3 exit the Sec61 translocon
      more rapidly in a process that suggests a displacement model for their
      integration where the biosynthesis of one transmembrane domain would facilitate
      the exit of another. In order to investigate this hypothesis further, we studied
      the integration of the first and third transmembrane domains of opsin in the
      absence of any additional C-terminal transmembrane domains. In the case of
      transmembrane domain 1, we found that its lateral exit from the translocon is
      clearly dependent upon the synthesis of subsequent transmembrane domains. By
      contrast, the lateral exit of the third transmembrane domain occurred
      independently of any such requirement. Thus, even within a single polypeptide
      chain, distinct transmembrane domains display different requirements for their
      integration through the endoplasmic reticulum translocon, and the displacement of
      one transmembrane domain by another is not a global requirement for membrane
      integration.

PMID- 16787950
TI  - PKCbeta-dependent activation of RhoA by syndecan-4 during focal adhesion
      formation.
AB  - Syndecan-4 is a ubiquitously expressed transmembrane heparan sulphate
      proteoglycan acting in concert with integrins in the formation of focal adhesions
      and stress fibres. Signalling events studied thus far suggest the formation of a
      ternary complex between syndecan-4, phosphatidylinositol 4,5-bisphosphate and
      protein kinase C alpha (PKCalpha). Syndecan-4 clustering at the cell surface has
      also been associated with RhoA-dependent signalling, but the relationship between
      PKCalpha and RhoA has not been resolved. Here we present evidence that syndecan
      4, PKCalpha and RhoA are in a linear pathway necessary for the formation and
      maintenance of stress fibres in primary rat embryo fibroblasts. Inhibition of
      PKCalpha activity through the use of specific pharmacological inhibitors, a
      dominant-negative construct, or siRNA downregulation of protein levels,
      attenuated focal adhesion formation and the maintenance of stress fibres.
      However, these effects could be bypassed through independent activation of RhoA
      with lysophosphatidic acid, but not by clustering of syndecan-4 with ligand.
      Furthermore, inhibition of PKCalpha could block the increase in the GTP levels of
      RhoA induced by clustering of syndecan-4 at the cell surface. All these data
      point to a mechanism whereby syndecan-4 signals to RhoA in a PKCalpha-dependent
      manner and PKCalpha directly influences RhoA activity.

PMID- 16787951
TI  - In vitro antimycoplasmal activity of Melaleuca alternifolia essential oil.

PMID- 16787952
TI  - Comparative activity of the new lipoglycopeptide telavancin in the presence and
      absence of serum against 50 glycopeptide non-susceptible staphylococci and three
      vancomycin-resistant Staphylococcus aureus.
AB  - BACKGROUND: Telavancin, a new multifunctional lipoglycopeptide antibiotic,
      exhibits broad-spectrum Gram-positive activity against a variety of pathogens. We
      examined the effects of human serum and antimicrobial concentrations on the
      activity of telavancin against glycopeptide-intermediate staphylococcal species
      (GISS), heteroresistant GISS (hGISS) and three vancomycin-resistant
      Staphylococcus aureus (VRSA) compared with vancomycin, quinupristin/dalfopristin,
      linezolid and daptomycin. METHODS: MIC and MBCs were performed against all
      antimicrobials. Time-kill experiments were performed using two strains of GISS
      (Mu50; NJ992) and VRSA (VRSAMI; VRSAPA) at 1, 2, 4, 8, 16 and 32x MIC. Telavancin
      and daptomycin were evaluated in the presence and absence of serum. RESULTS: All
      GISS and hGISS were susceptible to the tested agents with telavancin and
      quinupristin/dalfopristin demonstrating the lowest MIC, followed by daptomycin,
      linezolid and vancomycin. Against VRSA, daptomycin and quinupristin/dalfopristin
      had the lowest MIC, followed by linezolid, telavancin and vancomycin. In the
      presence of serum, telavancin and daptomycin MICs increased 1- to 4-fold.
      Concentration-dependent activity was demonstrated by telavancin and daptomycin,
      in the presence and absence of serum. Telavancin and daptomycin were bactericidal
      against GISS and performed similarly in the presence of serum.
      Quinupristin/dalfopristin demonstrated bactericidal activity at clinically
      achievable concentrations, whereas linezolid was bacteriostatic. CONCLUSIONS:
      Telavancin demonstrated concentration-dependent bactericidal activity against
      GISS, hGISS and VRSA at concentrations equal to or above 4x MIC, which
      corresponds to therapeutic levels against GISS and clinically achieved
      concentrations against the VRSA. Similar to daptomycin, telavancin activity was
      diminished in the presence of serum but bactericidal activity was maintained.
      Further investigation with telavancin against GISS, hGISS and VRSA is warranted.

PMID- 16787953
TI  - Determination of gentamicin in different matrices by a new sensitive high
      performance liquid chromatography-mass spectrometric method.
AB  - OBJECTIVES: The aim of this work was to develop and validate an HPLC method for
      gentamicin quantification in different types of biological samples such as animal
      tissues and cellular material and also in pharmaceuticals. METHODS: Poly(lactide
      co-glycolide) microparticles (MP) of gentamicin (PLGA 502H MP), THP-1 cells, and
      plasma and tissue samples of mice treated with the antibiotic either free or
      loaded into PLGA 502H MP were processed by a simple preparation procedure,
      subjected to chromatography on a reversed-phase column and measured by mass
      spectrometry detection. The developed method was compared with bioassay and
      fluorimetric assay methods previously used for gentamicin determination. RESULTS:
      The HPLC method was linear over the ranges 40-800 ng/mL and 0.1-100 microg/mL and
      showed good accuracy (average accuracy < 5.59%) and reproducibility (CV < 6.13%).
      Encapsulation of gentamicin in PLGA 502H MP was determined by the three methods.
      Good correlation was observed between bioassay (reference method) and HPLC. Extra
      and intracellular in vitro antibiotic accumulation was determined by bioassay
      and chromatography. Both methods gave similar extracellular concentrations but
      the HPLC-MS technique demonstrated an improved accuracy (5.59% versus 14%) and
      precision (6.13% versus 15%) compared with bioassay. However, only the HPLC-MS
      method was sensitive enough to detect the drug, intracellularly and in tissues.
      CONCLUSIONS: All these data favour the use of chromatography-mass spectrometry as
      a versatile technique not only suitable for gentamicin quantification loaded in
      drug delivery systems, but also sensitive and specific enough for in vivo and
      intracellular studies.

PMID- 16787954
TI  - Reversing methicillin resistance in MRSA using a bacterial transforming agent.
AB  - BACKGROUND: Antimicrobial resistance in staphylococci remains a significant
      problem in the clinical management of infections. New therapeutic entities are
      required for the prophylaxis and treatment of staphylococcal infection including
      those caused by methicillin-resistant Staphylococcus aureus (MRSA). Potential
      candidates include bacterial transforming agents (BTAs), compounds that can
      potentiate the activity of cell-wall-active antimicrobials by hypersensitizing
      the bacterial cell wall to the bactericidal effects of these drugs. BTAs have
      been found to inhibit MRSA in vitro when administered in combination with
      established antibiotics. OBJECTIVES: To examine the antimicrobial potential of a
      known BTA (BTA 19976a) on strains of MRSA in vitro. METHODS: Etest and time-kill
      methodologies were employed to assess the inhibitory potential of BTA at 10% w/v
      on strains of E-MRSA-3, E-MRSA-15 and E-MRSA-16. RESULTS: Etests demonstrated a
      reduction in the oxacillin MIC for E-MRSA-3, E-MRSA-15 and the NCTC 12493
      reference strain of MRSA when exposed to BTA at 10% w/v. Time-kill assays
      similarly demonstrated a reduction in viable counts for organisms exposed to
      methicillin at 40 mg/L+BTA at 10% w/v, compared with methicillin alone, an effect
      which varied in cidality, pattern of killing and regrowth between strains.
      CONCLUSIONS: The antimicrobial effects of this BTA on MRSA are encouraging and
      warrant further investigation with large numbers of different epidemic strains
      and a comprehensive PK/PD evaluation. This could lead to new therapeutic entities
      for the prophylaxis and treatment of staphylococcal infections.

PMID- 16787955
TI  - Selective coronary artery plaque visualization and differentiation by contrast
      enhanced inversion prepared MRI.
AB  - AIMS: We sought to evaluate the utility of contrast-enhanced coronary magnetic
      resonance imaging (CE-MRI) for selective visualization and non-invasive
      differentiation of atherosclerotic coronary plaque in humans. METHODS AND
      RESULTS: Nine patients with coronary artery disease (CAD) as confirmed by X-ray
      angiography and multidetector computed tomography (MDCT) were studied by T1
      weighted black blood inversion recovery coronary MRI before (N-IR) and after
      administration of Gd-DTPA (CE-IR). Plaques were categorized as calcified, non
      calcified, and mixed based on their Hounsfield number derived from MDCT. With
      MDCT, a total of 29 plaques were identified, including calcified (n=6), non
      calcified (n=6), and mixed calcified/non-calcified (n=17). On N-IR MRI, 26
      plaques (90%) were dark, whereas three plaques (two non-calcified and one mixed)
      appeared bright. On CE-MRI, 13/29 (45%) plaques, 11 of which were mixed, one non
      calcified, and one calcified showed contrast uptake. All others remained dark.
      CONCLUSION: In this preliminary study, we demonstrate the potential utility of CE
      IR MRI for selective plaque visualization and differentiation of plaque types.
      The observed contrast uptake may be associated with endothelial dysfunction,
      neovascularization, inflammation, and/or fibrosis.

PMID- 16787956
TI  - The use of primary care databases: case-control and case-only designs.
AB  - Study designs based on the identification of cases are frequently utilized when
      undertaking epidemiological research. Traditionally these have been mainly based
      on identification of cases from hospital records. This paper discusses the use of
      study designs based on the identification of cases focusing on their application
      to research data derived from primary care. The designs are discussed in the
      context of using computerized clinical data derived from primary care. The
      traditional case-control design is considered, with emphasis on the
      identification of cases and the selection of controls. A common problem when
      using primary care research databases is that information about potential
      confounding variables is often limited. Case-only designs, specifically the case
      crossover and the within-person case-series, offer alternative designs that aim
      to overcome problems with confounding. The principles underlying these case-only
      designs are presented along with examples of their use. The advantages and
      limitations of the different designs are discussed.

PMID- 16787957
TI  - Cluster randomized trial of a multifaceted primary care decision-support
      intervention for inherited breast cancer risk.
AB  - BACKGROUND: GPs are increasingly expected to meet the needs of patients concerned
      about their risk of inherited breast cancer, but may lack skills or confidence to
      use complex management guidelines. We developed an evidence-based, multifaceted
      intervention intended to promote confidence and skills in this area. OBJECTIVE:
      To evaluate the effectiveness of the intervention in improving GP confidence in
      managing patients concerned about genetic risk of breast cancer. METHODS: 
      DESIGN: Cluster randomized controlled trial. SETTING: General practices in the
      Grampian region of Scotland. SUBJECTS: GPs and the patients they referred for
      genetic counselling for risk of breast cancer. MAIN OUTCOME MEASURES: GPs' self
      reported confidence in four activities related to genetics; rates of referral of
      patients at elevated genetic risk; and referred patients' understanding of cancer
      risk factors. RESULTS: No statistically significant differences were observed
      between intervention and control arms in the primary or secondary outcomes. A
      possible effect of the intervention on the proportion of referred patients who
      were at elevated risk could not be discounted. Only a small proportion of
      intervention GPs attended the educational session, were aware or the software, or
      made use of it in practice. CONCLUSIONS: No convincing evidence of the
      effectiveness of the intervention was found, probably reflecting barriers to its
      use in routine practice.

PMID- 16787958
TI  - Prognostic factors and clinical outcome in acute lower respiratory tract
      infections: a prospective study in general practice.
AB  - BACKGROUND: Unrealistic expectations about illness duration are likely to result
      in reconsultations and associated unnecessary antibiotic prescriptions. An
      evidence-based account of clinical outcomes in patients with lower respiratory
      tract infection (LRTI) may help avoid unnecessary antibiotic prescriptions and
      reconsultations. OBJECTIVES: We aimed to identify clinical factors that may
      predict a prolonged clinical course or poor outcome for patients with LRTI and to
      provide an evidence-based account of duration of an LRTI and the impact of the
      illness on daily activities in patients consulting in general practice. METHODS:
      A prospective cohort study of 247 adult patients with a clinical diagnosis of
      LRTI presenting to 25 GPs in The Netherlands was carried out. Multivariable Cox
      regression analysis was used to identify baseline clinical and infection
      parameters that predicted the time taken for symptoms to resolve. A Kaplan-Meier
      curve was used to analyse time-to-symptom resolution. Clinical cure was recorded
      by the GPs at 28 days after the initial consultation and by the patients at 27
      days. RESULTS: Co-morbidity of asthma was a statistically significant predictor
      of delayed symptom resolution, whereas the presence of fever, perspiring and the
      prescription of an antibiotic weakly predicted enhanced symptom resolution. The
      GPs considered 89% of the patients clinically cured at 28 days, but 43% of these
      nevertheless reported ongoing symptoms. Patient-reported cure was much lower
      (51%), and usual daily activities were limited in 73% of the patients at
      baseline, and 19% at final follow-up. CONCLUSIONS: The course of LRTI was
      generally uncomplicated, but the morbidity of this illness was considerable with
      a longer duration than generally reported, especially for patients with co
      existent asthma. These results underline once again the importance of providing
      GPs with an evidence-based account of outcomes to share with patients in order to
      set realistic expectations and of enhancing their communication skills within the
      consultation.

PMID- 16787959
TI  - Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects.
AB  - Metabolically healthy skeletal muscle possesses the ability to switch easily
      between glucose and fat oxidation in response to homeostatic signals. In type 2
      diabetes mellitus and obesity, the skeletal muscle shows a great reduction in
      this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to
      increase skeletal muscle glycogen stores via succinyl-CoA formation, might both
      postpone the fatigue and increase fatty acid utilization, since it does not
      affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects,
      the effect of an oral C-12 load was compared with a glucose or water load during
      prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by
      a mathematical model. After C-12, diabetics were able to complete the 2 h of
      exercise. Nonesterified fatty acids increased both during and after the exercise
      in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and
      the sum of C-12 plus lipids oxidized after the C-12 meal was significantly
      greater than lipids oxidized after the glucose meal (P < 0.025). The fraction of
      C-12 that entered the central compartment was 47% of that ingested. During the
      first phase of the exercise ( approximately 60 min), the mean C-12 clearance from
      the central compartment toward tissues was 2.57 and 1.30 l/min during the second
      phase of the exercise. In conclusion, C-12 seems to be a suitable energy
      substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized,
      and does not stimulate insulin secretion, which implies that lipolysis is not
      inhibited as reported after glucose ingestion.

PMID- 16787960
TI  - Long-lived alphaMUPA transgenic mice exhibit pronounced circadian rhythms.
AB  - Robust biological rhythms have been shown to affect life span. Biological clocks
      can be entrained by two feeding regimens, restricted feeding (RF) and caloric
      restriction (CR). RF restricts the time of food availability, whereas CR
      restricts the amount of calories with temporal food consumption. CR is known to
      retard aging and extend life span of animals via yet-unknown pathways. We
      hypothesize that resetting the biological clock could be one possible mechanism
      by which CR extends life span. Because it is experimentally difficult to uncouple
      calorie reduction from temporal food consumption, we took advantage of the murine
      urokinase-like plasminogen activator (alphaMUPA) transgenic mice overexpressing a
      serine protease implicated in brain development and plasticity; they exhibit
      spontaneously reduced eating and increased life span. Quantitative real-time PCR
      analysis revealed that alphaMUPA mice exhibit robust expression of the clock
      genes mPer1, mPer2, mClock, and mCry1 but not mBmal1 in the liver. We also found
      changes in the circadian amplitude and/or phase of clock-controlled output
      systems, such as feeding behavior, body temperature, and enteric cryptdin
      expression. A change in the light-dark regimen led to modified clock gene
      expression and abrogated circadian patterns of food intake in wild-type (WT) and
      alphaMUPA mice. Consequently, food consumption of WT mice increased, whereas that
      of alphaMUPA mice remained the same, indicating that reduced food intake occurs
      upstream and independently of the biological clock. Thus we surmise that CR could
      lead to pronounced and synchronized biological rhythms. Because the biological
      clock controls mitochondrial, hormonal, and physiological parameters, system
      synchronicity could lead to extended life span.

PMID- 16787961
TI  - Angiotensin II decreases system A amino acid transporter activity in human
      placental villous fragments through AT1 receptor activation.
AB  - Reduced transport of amino acids from mother to fetus can lead to fetal
      intrauterine growth restriction (IUGR). The activities of several amino acid
      transport systems, including system A, are decreased in placental
      syncytiotrophoblast of IUGR pregnancies. Na(+)-K(+)-ATPase activity provides an
      essential driving force for Na(+)-coupled system A transport, is decreased in the
      placenta of IUGR pregnancies, and is decreased by angiotensin II in several
      tissues. Several reports have shown activation of the fetoplacental renin
      angiotensin system (RAS) in IUGR. We investigated the effect of angiotensin II on
      placental system A transport and Na(+)-K(+)-ATPase activity in placental villi.
      Placental system A activity in single primary villous fragments was measured as
      the Na(+)-dependent uptake of alpha-(methylamino)isobutyric acid, and Na(+)/K(+)
      ATPase activity was measured as ouabain-sensitive uptake of (86)rubidium.
      Angiotensin II decreased system A activity in a concentration-dependent fashion
      (10-500 nmol/l). Angiotensin II type 1 receptor (AT1-R) antagonists losartan and
      AT1-R anti-peptide blocked the angiotensin II effect, but the angiotensin II type
      2 receptor antagonist PD-123319 was without effect. System A activity was not
      altered by preincubation with AT1-R-independent vasoconstrictors, and
      antioxidants did not prevent the decrease in activity mediated by angiotensin II.
      Angiotensin II decreased Na(+)-K(+)-ATPase activity by an AT1-R dependent
      mechanism, and inhibition of Na(+)-K(+)-ATPase activity decreased system A
      activity in a dose-response fashion. These data suggest that angiotensin II, via
      AT1-R signaling, decreases system A activity by suppressing Na(+)-K(+)-ATPase in
      human placental villi, consistent with possible adverse effects of enhanced
      placental RAS on fetal growth.

PMID- 16787962
TI  - DHEA enhances effects of weight training on muscle mass and strength in elderly
      women and men.
AB  - The plasma levels of dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS)
      decline approximately 80% between the ages of 25 and 75 yr. Muscle mass and
      strength also decrease with aging. Published data on the effects of DHEA
      replacement on muscle mass and strength are conflicting. The goals of this study
      were to determine whether DHEA replacement increases muscle mass and strength
      and/or enhances the effects of heavy resistance exercise in elderly women and
      men. We conducted a randomized, double-blind, placebo-controlled study of the
      effects of 10 mo of DHEA replacement therapy with the addition of weightlifting
      exercise training during the last 4 mo of the study (DHEA + exercise group, n =
      29; placebo + exercise group, n = 27). DHEA alone for 6 mo did not significantly
      increase strength or thigh muscle volume. However, DHEA therapy potentiated the
      effect of 4 mo of weightlifting training on muscle strength, evaluated by means
      of one-repetition maximum measurement and Cybex dynamometry, and on thigh muscle
      volume, measured by magnetic resonance imaging. Serum insulin-like growth factor
      concentration increased in response to DHEA replacement. This study provides
      evidence that DHEA replacement has the beneficial effect of enhancing the
      increases in muscle mass and strength induced by heavy resistance exercise in
      elderly individuals.

PMID- 16787964
TI  - Laser-Doppler flowmetry reveals rapid perfusion changes in adipose tissue of lean
      and obese females.
AB  - The present study aimed to evaluate adipose tissue blood flow (ATBF) by means of
      laser-Doppler flowmetry (LDF) in humans. Lower body negative pressure (LBNP) and
      straining known to affect epidermal blood flow through the autonomic nervous
      system were performed in 11 lean and 11 obese female volunteers. ATBF changes
      were compared between both groups and also discriminated from skin blood flow
      (SBF) responses of the immediate vicinity. Additionally, LDF measurements were
      compared with flow measurements using (133)xenon washout in 10 lean subjects
      during whole body cooling. LDF estimations of SBF and ATBF showed a positive
      correlation to (133)Xe during cooling. SBF and ATBF were reduced to the same
      extent in both lean and obese subjects during LBNP. Straining induced divergent
      changes in SBF and ATBF: initially SBF decreased while ATBF increased, but toward
      the end of straining SBF increased above baseline and ATBF returned down to
      baseline level. Those changes were similar in both weight groups. Interestingly,
      only in obese subjects, both LBNP and straining were followed by ATBF
      augmentation, while SBF levels remained stable. In conclusion, LDF compares with
      (133)Xe washout in monitoring ATBF during tonic perfusion changes. Its strength,
      however, lies in the detection of rapid flow alterations within the subcutaneous
      tissue, allowing the evaluation of reflex responses of the subcutaneous
      microcirculation. Interestingly, those rapid changes in SBF and ATBF can be both
      concordant and discordant. With regard to ATBF, vasoconstrictor components of the
      reflex responses were similar in lean and obese subjects, whereas vasodilatory
      responses were more pronounced in obese volunteers.

PMID- 16787963
TI  - Characterization and regulation of the gene expression of amino acid transport
      system A (SNAT2) in rat mammary gland.
AB  - Amino acid transport via system A plays an important role during lactation,
      promoting the uptake of small neutral amino acids, mainly alanine and glutamine.
      However, the regulation of gene expression of system A [sodium-coupled neutral
      amino acid transporter (SNAT)2] in mammary gland has not been studied. The aim of
      the present work was to understand the possible mechanisms of regulation of SNAT2
      in the rat mammary gland. Incubation of gland explants in amino acid-free medium
      induced the expression of SNAT2, and this response was repressed by the presence
      of small neutral amino acids or by actinomycin D but not by large neutral or
      cationic amino acids. The half-life of SNAT2 mRNA was 67 min, indicating a rapid
      turnover. In addition, SNAT2 expression in the mammary gland was induced by
      forskolin and PMA, inducers of PKA and PKC signaling pathways, respectively.
      Inhibitors of PKA and PKC pathways partially prevented the upregulation of SNAT2
      mRNA during adaptive regulation. Interestingly, SNAT2 mRNA was induced during
      pregnancy and to a lesser extent at peak lactation. beta-Estradiol stimulated the
      expression of SNAT2 in mammary gland explants; this stimulation was prevented by
      the estrogen receptor inhibitor ICI-182780. Our findings clearly demonstrated
      that the SNAT2 gene is regulated by multiple pathways, indicating that the
      expression of this amino acid transport system is tightly controlled due to its
      importance for the mammary gland during pregnancy and lactation to prepare the
      gland for the transport of amino acids during lactation.

PMID- 16787965
TI  - Chronic subcutaneous administration of kisspeptin-54 causes testicular
      degeneration in adult male rats.
AB  - The kisspeptins are KiSS-1 gene-derived peptides that signal through the G
      protein-coupled receptor-54 (GPR54) and have recently been shown to be critical
      regulators of reproduction. Acute intracerebroventricular or peripheral
      administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG)
      axis. This effect is thought to be mediated via the hypothalamic gonadotropin
      releasing hormone (GnRH) system. Chronic administration of GnRH agonists
      paradoxically suppresses the HPG axis after an initial agonistic stimulation. We
      investigated the effects of continuous peripheral kisspeptin administration in
      male rats by use of Alzet minipumps. Initially we compared the effects of acute
      subcutaneous administration of kisspeptin-10, -14, and -54 on the HPG axis.
      Kisspeptin-54 produced the greatest increase in plasma LH and total testosterone
      at 60 min postinjection and was used in the subsequent continuous administration
      experiments. Chronic subcutaneous long-term administration of 50 nmol kisspeptin
      54/day for 13 days decreased testicular weight. Histological examination showed
      degeneration of the seminiferous tubules associated with a significant decrease
      in the circulating levels of the testes-derived hormone, inhibin B. Plasma free
      and total testosterone were also lower, although these changes did not reach
      statistical significance. Further studies examined the effects of shorter periods
      of continuous kisspeptin administration. Subcutaneous administration of 50 nmol
      kisspeptin-54 for 1 day increased plasma LH and testosterone. This effect was
      lost after 2 days of administration, suggesting a downregulation of the HPG axis
      response to kisspeptin following continuous administration. These findings
      indicate that kisspeptin may provide a novel tool for the manipulation of the HPG
      axis and spermatogenesis.

PMID- 16787966
TI  - Chromosome-wide, allele-specific analysis of the histone code on the human X
      chromosome.
AB  - Variation in the composition of chromatin has been proposed to generate a
      'histone code' that epigenetically regulates gene expression in a variety of
      eukaryotic systems. As a result of the process of X chromosome inactivation,
      chromatinon the mammalian inactive X chromosome (Xi) is marked by several
      modifications, including histone hypoacetylation, trimethylation of lysine 9 on
      histone H3 (H3TrimK9) and substitution of core histone H2A with the histone
      variant MacroH2A. H3TrimK9 is a well-studied marker for heterochromatin in many
      organisms, but the distribution and function of MacroH2A are less clear.
      Cytologically, the Xi in human cells comprises alternating and largely non
      overlapping approximately 10-15 Mb domains marked by MacroH2A and H3TrimK9. To
      examine the genomic deposition of MacroH2A, H3TrimK9 and acetylated histone H4
      modifications on the Xi at higher resolution, we used chromatin
      immunoprecipitation in combination with a SNP-based assay to distinguish the Xi
      and active X (Xa) in a diploid female cell line and to determine quantitatively
      the relative enrichment of these histone code elements on the Xi relative to the
      Xa. Although we found a majority of sites were enriched for either MacroH2A or
      H3TrimK9 in a manner consistent with the cytological appearance of the Xi, a
      range of different histone code types were detected at different sites along the
      X. These findings suggest that the nature of the heterochromatin histone code
      associated with X inactivation may be more heterogeneous than previously thought
      and imply that gene silencing can be achieved by a variety of different
      epigenetic mechanisms whose genomic, evolutionary or developmental basis is now
      amenable to investigation.

PMID- 16787967
TI  - Mouse MAELSTROM: the link between meiotic silencing of unsynapsed chromatin and
      microRNA pathway?
AB  - Meiotic silencing of unsynapsed chromatin (MSUC) is a key mechanism in
      spermatogenesis and a model system to study the dynamics of gene silencing. Here
      we show that MAEL, the ortholog of Drosophila's high mobility group box protein
      Maelstrom, is associated not only with the silenced XY body, but also with
      unsynapsed autosomes. Characterization of MAEL revealed that it interacts
      directly with the chromatin remodeler SNF5/INI1 and chromatin-associated protein
      SIN3B, which we also find localized to the XY body. This is the first time that a
      chromatin remodeler has been shown to associate with whole chromosomes. In
      addition, we show that MAEL is a component of the mouse meiotic nuage and its
      haploid cell counterpart, the chromatoid body. This is a site of accumulation of
      RNA and RNA processing enzymes, including proteins involved in the microRNA
      (miRNA) pathway. Furthermore, in the nuage, MAEL is present in a complex with
      germ cell specific MVH, an RNA helicase and Argonaute family members, MILI and
      MIWI. The presence of MAEL in these critical compartments of male germ cells and
      its interactions provide a link suggesting the involvement of the miRNA pathway
      in MSUC.

PMID- 16787968
TI  - Additional gene ontology structure for improved biological reasoning.
AB  - MOTIVATION: The Gene Ontology (GO) is a widely used terminology for gene product
      characterization in, for example, interpretation of biology underlying microarray
      experiments. The current GO defines term relationships within each of the
      independent subontologies: molecular function, biological process and cellular
      component. However, it is evident that there also exist biological relationships
      between terms of different subontologies. Our aim was to connect the three
      subontologies to enable GO to cover more biological knowledge, enable a more
      consistent use of GO and provide new opportunities for biological reasoning.
      RESULTS: We propose a new structure, the Second Gene Ontology Layer, capturing
      biological relations not directly reflected in the present ontology structure.
      Given molecular functions, these paths identify biological processes where the
      molecular functions are involved and cellular components where they are active.
      The current Second Layer contains 6271 validated paths, covering 54% of the
      molecular functions of GO and can be used to render existing gene annotation sets
      more complete and consistent. Applying Second Layer paths to a set of 4223 human
      genes, increased biological process annotations by 24% compared to publicly
      available annotations and reproduced 30% of them. AVAILABILITY: The Second GO is
      publicly available through the GO Annotation Toolbox (GOAT.no):
      http://www.goat.no.

PMID- 16787970
TI  - A reference database for circular dichroism spectroscopy covering fold and
      secondary structure space.
AB  - MOTIVATION: Circular Dichroism (CD) spectroscopy is a long-established technique
      for studying protein secondary structures in solution. Empirical analyses of CD
      data rely on the availability of reference datasets comprised of far-UV CD
      spectra of proteins whose crystal structures have been determined. This article
      reports on the creation of a new reference dataset which effectively covers both
      secondary structure and fold space, and uses the higher information content
      available in synchrotron radiation circular dichroism (SRCD) spectra to more
      accurately predict secondary structure than has been possible with existing
      reference datasets. It also examines the effects of wavelength range, structural
      redundancy and different means of categorizing secondary structures on the
      accuracy of the analyses. In addition, it describes a novel use of hierarchical
      cluster analyses to identify protein relatedness based on spectral properties
      alone. The databases are shown to be applicable in both conventional CD and SRCD
      spectroscopic analyses of proteins. Hence, by combining new bioinformatics and
      biophysical methods, a database has been produced that should have wide
      applicability as a tool for structural molecular biology.

PMID- 16787969
TI  - Transcript mapping with high-density oligonucleotide tiling arrays.
AB  - MOTIVATION: High-density DNA tiling microarrays are a powerful tool for the
      characterization of complete transcriptomes. The two major analytical challenges
      are the segmentation of the hybridization signal along genomic coordinates to
      accurately determine transcript boundaries and the adjustment of the sequence
      dependent response of the oligonucleotide probes to achieve quantitative
      comparability of the signal between different probes. RESULTS: We describe a
      dynamic programming algorithm for finding a globally optimal fit of a piecewise
      constant expression profile along genomic coordinates. We developed a probe
      specific background correction and scaling method that employs empirical probe
      response parameters determined from reference hybridizations with no need for
      paired mismatch probes. This combined analysis approach allows the accurate
      determination of dynamical changes in transcription architectures from
      hybridization data and will help to study the biological significance of complex
      transcriptional phenomena in eukaryotic genomes. AVAILABILITY: R package
      tilingArray at http://www.bioconductor.org.

PMID- 16787971
TI  - Increasing confidence of protein interactomes using network topological metrics.
AB  - MOTIVATION: Experimental limitations in high-throughput protein-protein
      interaction detection methods have resulted in low quality interaction datasets
      that contained sizable fractions of false positives and false negatives. Small
      scale, focused experiments are then needed to complement the high-throughput
      methods to extract true protein interactions. However, the naturally vast
      interactomes would require much more scalable approaches. RESULTS: We describe a
      novel method called IRAP* as a computational complement for repurification of the
      highly erroneous experimentally derived protein interactomes. Our method involves
      an iterative process of removing interactions that are confidently identified as
      false positives and adding interactions detected as false negatives into the
      interactomes. Identification of both false positives and false negatives are
      performed in IRAP* using interaction confidence measures based on network
      topological metrics. Potential false positives are identified amongst the
      detected interactions as those with very low computed confidence values, while
      potential false negatives are discovered as the undetected interactions with high
      computed confidence values. Our results from applying IRAP* on large-scale
      interaction datasets generated by the popular yeast-two-hybrid assays for yeast,
      fruit fly and worm showed that the computationally repurified interaction
      datasets contained potentially lower fractions of false positive and false
      negative errors based on functional homogeneity. AVAILABILITY: The confidence
      indices for PPIs in yeast, fruit fly and worm as computed by our method can be
      found at our website http://www.comp.nus.edu.sg/~chenjin/fpfn.

PMID- 16787973
TI  - DomainSieve: a protein domain-based screen that led to the identification of dam
      associated genes with potential link to DNA maintenance.
AB  - MOTIVATION: The Dam methyltransferase (DamMT) activity, broadly distributed in
      association with restriction endonucleases, as part of the restriction
      modification defense systems, has evolved to become intimately associated with
      essential biological functions in a few organisms. In Escherichia coli, DamMT is
      involved in multiple aspects of DNA maintenance, replication initiation, daughter
      chromosome segregation, DNA mismatch repair, gene expression control, etc. The
      participation of DamMT in such a diverse set of functions required that other
      genes adapted, or emerged through evolution, in response to the DamMT-induced
      modification of the genomic environment. One example is SeqA, a protein that
      senses the methylation status of the origin of replication of the chromosome to
      control the timing of replication initiation. Interestingly, seqA is only present
      in a few DamMT-specifying proteobacteria. This observation led us to hypothesize
      that other genes, specifying related functions, might also be found in these
      organisms. To test this hypothesis, we implemented a large-scale comparative
      genomic screen meant to identify genes specifying DNA methylation sensing
      domains, probably involved in DNA maintenance functions. RESULTS: We carried out
      a phylogenetic analysis of DamMT, identifying two contrasting behaviors of the
      protein. Based on this phylogeny, we defined precisely a set of genomes, in which
      the protein activity is likely to be involved in DNA maintenance functions, the
      'resident' dam genomes. We defined a second set of genomes, in which DamMT is not
      resident. We developped a new tool, 'DomainSieve', in order to screen these two
      sets for protein domains that are strictly associated with 'resident' dam
      genomes. This approach was rewarding and generated a list of genes, among which
      some, at least, specify activities with clear linkage to DamMT-dependent DNA
      methylation and DNA maintenance. AVAILABILITY: DomainSieve is implemented as a
      web resource and is accessible at http://stat.genopole.cnrs.fr/ds/.

PMID- 16787974
TI  - HCNet: a database of heart and calcium functional network.
AB  - SUMMARY: The Heart and Calcium functional Network (HCNet) database is a
      collection of functional gene modules calculated from the microarray data
      compendium available from the GEO database. It is a specialized database designed
      to assist experimentalists for cardiac calcium signaling research by providing
      the pre-calculated gene clusters and their potential correlation network in
      heart. In the current release of HCNet, 57 functional modules from 786 target
      genes obtained by a bi-clustering analysis of 381 microarray datasets are
      available. Detailed information of the clusters such as expression profiles,
      network diagrams is provided in two categories, heart-specific genes and heart
      specific genes along with calcium toolkit genes. Overrepresented gene ontological
      categories and transcription factors in each cluster are also provided to infer
      the biological implications of the detected functional modules. AVAILABILITY:
      HCNet is available at http://sbrg2.gist.ac.kr/hcnet.

PMID- 16787975
TI  - TSSub: eukaryotic protein subcellular localization by extracting features from
      profiles.
AB  - This paper introduces a new subcellular localization system (TSSub) for
      eukaryotic proteins. This system extracts features from both profiles and amino
      acid sequences. Four different features are extracted from profiles by four
      probabilistic neural network (PNN) classifiers, respectively (the amino acid
      composition from whole profiles; the amino acid composition from the N-terminus
      of profiles; the dipeptide composition from whole profiles and the amino acid
      composition from fragments of profiles). In addition, a support vector machine
      (SVM) classifier is added to implement the residue-couple feature extracted from
      amino acid sequences. The results from the five classifiers are fused by an
      additional SVM classifier. The overall accuracies of this TSSub reach 93.0 and
      77.4% on Reinhardt and Hubbard's eukaryotic protein dataset and Huang and Li's
      eukaryotic protein dataset, respectively. The comparison with existing methods
      results shows TSSub provides better prediction performance than existing methods.
      AVAILABILITY: The web server is available from
      http://166.111.24.5/webtools/TSSub/index.html.

PMID- 16787976
TI  - Cleaver: software for identifying taxon specific restriction endonuclease
      recognition sites.
AB  - Cleaver is an application for identifying restriction endonuclease recognition
      sites that occur in some taxa but not in others. Differences in DNA fragment
      restriction patterns among taxa are the basis for many diagnostic assays for
      taxonomic identification and are used in procedures for removing the DNA of some
      taxa from pools of DNA from mixed sources. Cleaver analyses restriction digestion
      of groups of orthologous DNA sequences simultaneously to allow identification of
      differences in restriction pattern among the fragments derived from different
      taxa. AVAILABILITY: Cleaver is freely available without registration from its
      website (http://cleaver.sourceforge.net/) and can be copied, modified and re
      distributed under the terms of the GNU general public licence version2
      (http://www.gnu.org/licences/gpl). The program can be run as a script for
      computers that have Python 2.3 and necessary extra modules installed. This allows
      it to run on Gnu/Linux, Unix, MacOSX and Windows platforms. Stand-alone
      executable versions for Windows and MacOSX operating systems are available.

PMID- 16787977
TI  - A lock-and-key model for protein-protein interactions.
AB  - MOTIVATION: Protein-protein interaction networks are one of the major post
      genomic data sources available to molecular biologists. They provide a
      comprehensive view of the global interaction structure of an organism's proteome,
      as well as detailed information on specific interactions. Here we suggest a
      physical model of protein interactions that can be used to extract additional
      information at an intermediate level: It enables us to identify proteins which
      share biological interaction motifs, and also to identify potentially missing or
      spurious interactions. RESULTS: Our new graph model explains observed
      interactions between proteins by an underlying interaction of complementary
      binding domains (lock-and-key model). This leads to a novel graph-theoretical
      algorithm to identify bipartite subgraphs within protein-protein interaction
      networks where the underlying data are taken from yeast two-hybrid experimental
      results. By testing on synthetic data, we demonstrate that under certain
      modelling assumptions, the algorithm will return correct domain information about
      each protein in the network. Tests on data from various model organisms show that
      the local and global patterns predicted by the model are indeed found in
      experimental data. Using functional and protein structure annotations, we show
      that bipartite subnetworks can be identified that correspond to biologically
      relevant interaction motifs. Some of these are novel and we discuss an example
      involving SH3 domains from the Saccharomyces cerevisiae interactome.
      AVAILABILITY: The algorithm (in Matlab format) is available (see
      http://www.maths.strath.ac.uk/~aas96106/lock_key.html).

PMID- 16787978
TI  - Why are manual workers at high risk of upper limb disorders? The role of physical
      work factors in a random sample of workers in France (the Pays de la Loire
      study).
AB  - OBJECTIVE: To investigate the reasons for the excess risk of upper limb
      musculoskeletal disorders among manual workers compared with other workers in a
      random sample of 2656 French men and women (20-59 years old) participating in a
      study on the prevalence of work related upper limb disorders conducted by
      France's National Institute of Health Surveillance. METHODS: Prevalence ratios
      (PR) of physician-diagnosed musculoskeletal disorders of the shoulder, elbow,
      wrist, and hand (any of six leading disorders, rotator cuff syndrome, carpal
      tunnel syndrome) in manual versus non-manual workers were calculated using Cox
      regression models with a constant time of follow up and robust variance. RESULTS:
      11.3% of men and 15.1% of women were diagnosed with an upper limb disorder. The
      risk was especially high in manual workers (PRs: 1.40 to 2.10). Physical work
      factors accounted for over 50% of occupational disparities overall, 62% (men) to
      67% (women) for rotator cuff syndrome, and 96% (women) for carpal tunnel
      syndrome. The authors calculated that under lower levels of physical work
      exposures, up to 31% of cases among manual workers could have been prevented.
      CONCLUSIONS: In working men and women, upper limb musculoskeletal disorders are
      frequent. Physical work exposures, such as repetitive and forceful movements, are
      an important source of risk and in particular account for a large proportion of
      excess morbidity among manual workers.

PMID- 16787979
TI  - Non-fatal occupational injuries in British agriculture.
AB  - OBJECTIVES: To investigate the incidence, nature and determinants of non-fatal
      occupational injuries in British agriculture. METHODS: As part of a postal
      survey, data on lifetime histories of work in agriculture and occupational
      accidents were obtained from men born between 1933 and 1977 and residing in three
      rural areas of England and Wales. Incidence rates for different categories of
      accident were compared with those derived from statutory reporting. Associations
      with risk factors were explored by Poisson regression, and summarised by
      incidence rate ratios (IRRs). RESULTS: Of the 10 765 responders (response rate =
      31%), 3238 (30%) reported at least one occupational accident at the ages of 14-64
      years, leading to absence from work for >or=3 days, including 1492 accidents that
      could be linked to a specific job listed in the history of agricultural work. The
      reported incidence of injuries in agriculture was markedly higher than that
      derived from statutory reporting, particularly for self-employed farmers. During
      1996-2003, the highest rates of agricultural accidents were from handling,
      lifting or carrying (4.9/1000 person-years), falls from a height (4.6/1000 person
      years) and injury by animals (3.4/1000 person-years). After adjustment for
      calendar period and age, the risk of accidents was elevated in men who had only
      recently entered agricultural work (IRR 3.7, 95% CI 2.7 to 5.1 for men who had
      worked in agriculture for up to 1 year relative to those who had entered the
      industry >25 years earlier), and in those who carried out forestry (IRR 1.7, 95%
      CI 1.5 to 1.9). CONCLUSION: Our findings confirm the substantial
      underascertainment of serious accidental injuries in agriculture through
      statutory reporting, particularly for the self-employed. The risk of accidents is
      highest in new recruits to the industry and in those undertaking forestry, and
      these groups should be a target for further preventive action.

PMID- 16787980
TI  - Associations of adiposity from childhood into adulthood with insulin resistance
      and the insulin-like growth factor system: 65-year follow-up of the Boyd Orr
      Cohort.
AB  - CONTEXT: One metabolic pathway through which adiposity influences disease risk
      may be via alterations in insulin and IGF metabolism. OBJECTIVE: Our objective
      was to investigate associations of adiposity at different stages of life with
      insulin and the IGF system. DESIGN, SETTING, AND PARTICIPANTS: The study was a 65
      yr follow-up of 728 Boyd Orr cohort participants (mean age, 71 yr) originally
      surveyed between 1937 and 1939. MAIN OUTCOMES: Outcomes included homeostasis
      model assessment of insulin resistance, total IGF-I and IGF-II, IGF binding
      protein (IGFBP)-2, and IGFBP-3 in adulthood. RESULTS: Childhood body mass index
      (BMI) was weakly inversely related to adult IGF-I (coefficient per BMI sd, -3.4
      ng/ml; 95% confidence interval, -7.3 to 0.5; P = 0.09). IGF-II (but not IGF-I)
      increased with higher current fat mass index (coefficient, 26.1 ng/ml; 95%
      confidence interval, 4.6 to 47.6; P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4
      to 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2 to 24.9; P < 0.001), and
      homeostasis model assessment of insulin resistance increased by 38.8% (28.9 to
      49.6; P < 0.001) per sd higher adult BMI. Among thin adults (BMI tertiles 1 and
      2), IGFBP-2 was positively, and insulin resistance was inversely, associated with
      childhood BMI. CONCLUSION: There was only weak evidence that associations of
      childhood BMI with chronic disease risk may be mediated by adult IGF-I levels.
      Circulating IGFBP-2 in adulthood, a marker for insulin sensitivity, was inversely
      associated with current adiposity, but overweight children who became relatively
      lean adults were more insulin sensitive than thinner children. The findings may
      indicate programming of later insulin sensitivity and consequently IGFBP-2 levels
      in response to childhood adiposity. The role of IGF-II in obesity-related chronic
      diseases warrants additional investigation.

PMID- 16787981
TI  - In men, peripheral estradiol levels directly reflect the action of estrogens at
      the hypothalamo-pituitary level to inhibit gonadotropin secretion.
AB  - CONTEXT: Estradiol inhibits gonadotropin release in men by an action at the
      hypothalamus and pituitary. Because of the tissue-specific regulation of
      aromatase, peripheral estradiol levels may not reflect brain estradiol
      concentrations. OBJECTIVE: We evaluated whether local aromatization of
      testosterone in the hypothalamus or pituitary is important for gonadotropin
      release and to what extent circulating estrogens affect gonadotropin levels and
      peripheral testosterone levels. DESIGN, SUBJECTS, AND INTERVENTIONS: We
      suppressed aromatase activity in 10 young healthy men with letrozole 2.5 mg once
      daily, restored plasma estradiol levels with estradiol patches (100 microg/d for
      the first week, 50 microg/d the second week, 25 microg/d the third week, and no
      estradiol patch the fourth week) and measured plasma testosterone, estradiol, LH,
      FSH, and SHBG levels. RESULTS: The mean estradiol and testosterone levels during
      the study ranged between 68.6 +/- 38.3 and 12.6 +/- 7.21 pg/ml for estradiol and
      179 +/- 91 and 955 +/- 292 ng/dl (mean +/- sd) for testosterone. Levels of
      testosterone, LH, and FSH were inversely related to peripheral estradiol levels.
      During letrozole use, the mean plasma estradiol level needed to restore
      testosterone, LH, and FSH levels to baseline levels was not significantly
      different from the baseline mean estradiol level. CONCLUSIONS: Local
      aromatization of testosterone in the hypothalamo-pituitary compartment is not a
      prerequisite for expression of the inhibitory action of estrogens on gonadotropin
      secretion in men. Peripheral estradiol levels directly reflect the inhibitory
      tone exerted by estrogens on gonadotropin release and are a major determinant of
      peripheral testosterone, LH, and FSH levels.

PMID- 16787982
TI  - Comprehensive mutation scanning of NF1 in apparently sporadic cases of
      pheochromocytoma.
AB  - BACKGROUND: Pheochromocytoma is a rare manifestation in patients with
      neurofibromatosis type 1 (NF 1). The 57-exon susceptibility gene NF1 has so far
      not been systematically scanned for unexpected germline mutations in individuals
      with sporadic pheochromocytoma. METHODS: Twenty-seven patients with bilateral
      adrenal and/or extraadrenal abdominal pheochromocytoma not carrying germline
      mutations of the genes VHL, RET, SDHB, and SDHD were selected from the European
      American pheochromocytoma registry. All 57 exons and flanking intronic regions of
      the NF1 gene were PCR amplified using newly designed primer pairs to exclude the
      amplification of pseudogenes. Intragenic mutation scanning was performed using
      denaturing HPLC and bidirectional direct sequencing. RESULTS: Of the 27
      apparently sporadic cases, one (4%) was found to have a pathogenic germline NF1
      mutation, Leu303Arg. Clinical reevaluation of this individual, who had bilateral
      pheochromocytoma, revealed classic, but very mild, features of NF 1, one
      cutaneous neurofibroma, axillary freckling, and Lisch nodules of the iris as well
      as a few cafe-au-lait spots. CONCLUSIONS: In the absence of germline mutations in
      VHL, RET, SDHD, and SDHB, patients with pheochromocytoma, especially with
      bilateral disease, should be checked thoroughly for clinical lesions suggestive
      of underlying syndromes such as the cutaneous and ophthalmological features
      characteristic of NF 1.

PMID- 16787983
TI  - Immune regulation of 25-hydroxyvitamin D-1alpha-hydroxylase in human monocytic
      THP1 cells: mechanisms of interferon-gamma-mediated induction.
AB  - CONTEXT: 25-Hydroxyvitamin D can be activated to 1,25-dihydroxyvitamin D(3)
      [1,25(OH)(2)D(3)] by the rate-limiting enzyme 1alpha-hydroxylase in cells of the
      immune system under control of immune stimuli, such as interferon-gamma
      (IFNgamma). In pathological situations, such as sarcoidosis, this can lead to
      systemic excess of 1,25(OH)(2)D(3) and hypercalcemia. OBJECTIVE: The aim of this
      study was to elucidate the intracellular pathways used by the immune system to
      tightly regulate 1,25(OH)(2)D(3) production in monocytes and macrophages. DESIGN:
      Human monocytic THP1-cells were differentiated and activated by IFNgamma and a
      secondary stimulus, such as lipopolysaccharide or phorbol myristate acetate.
      1alpha-Hydroxylase mRNA levels were quantified by real-time RT-PCR. The
      involvement of different signaling pathways in the regulation of this enzyme was
      investigated using specific pharmacological inhibitors, whereas phosphorylation
      of signal transducer and activator of transcription 1alpha and CCAAT/enhancer
      binding protein beta was investigated by Western blotting. RESULTS: In
      undifferentiated monocytic THP1 cells, IFNgamma needs to be combined with a
      second stimulus, such as lipopolysaccharide, to induce 1alpha-hydroxylase. In
      contrast, in phorbol myristate acetate-differentiated THP1 macrophages, IFNgamma
      alone induces 1alpha-hydroxylase and to much higher levels. Many different
      signaling pathways need to be activated concurrently to allow immune-mediated
      1alpha-hydroxylase up-regulation. We show involvement of the Janus kinase-signal
      transducer and activator of transcription, MAPK, and nuclear factor-kappaB
      pathways, with a crucial role for the transcription factor CCAAT/enhancer binding
      protein beta. Furthermore, histone remodeling involving histone deacetylases and
      histone acetylase p300 is required. CONCLUSION: The present findings indicate
      that IFNgamma-mediated 1,25(OH)(2)D(3) production, as observed in granulomatous
      diseases such as sarcoidosis, will take place only under conditions where the
      necessary other signaling pathways are also activated.

PMID- 16787984
TI  - Serum brain-derived neurotrophic factor concentrations in lean and overweight
      children and adolescents.
AB  - CONTEXT: Brain-derived neurotrophic factor (BDNF) and its receptor appear to be
      important components of the leptin-signaling cascade involved in energy
      homeostasis, and mice with BDNF or TrkB gene haploinsufficiency have excessive
      adiposity. Little is known about the relationship between adiposity and BDNF,
      particularly in children. OBJECTIVE: The objective of the study was to study the
      association of serum BDNF with measures of adiposity in children.
      DESIGN/SETTING/PATIENTS: BDNF was determined by a sandwich-type ELISA after an
      overnight fast in convenience sample of 328 subjects, aged 3-19 yr enriched for
      extreme obesity. In 43, BDNF was also measured before, and again 1 h after,
      consuming a high-energy content (787 kcal) milkshake. MAIN OUTCOME MEASURES:
      Measures included associations between BDNF and measures of adiposity. RESULTS:
      There were no significant univariate associations between log BDNF and adiposity
      measured by body mass index (BMI), BMI-Z score, or fat mass. However, in an
      analysis of covariance accounting for age, sex, race, pubertal status, and
      platelet count, BDNF was lower in overweight children (mean +/- sd, 39.8 +/- 24.8
      vs. 47.0 +/- 25.4 ng/dl, P = 0.03); in multiple regression analyses with log BDNF
      as the dependent variable, BMI (P = 0.03), BMI-Z (P = 0.01), and body fat (P <
      0.02) were all negatively associated with BDNF once age, pubertal status, and
      platelet count were included in the model. Ingestion of a meal did not
      significantly alter serum BDNF 1 h later (P = 0.26). CONCLUSIONS: Serum BDNF is
      lower in extremely overweight children and adolescents than those of normal
      weight. It remains to be determined whether obese individuals with low serum BDNF
      for age and platelet count have mutations that alter BDNF function.

PMID- 16787985
TI  - Clinical and biochemical characteristics of a male patient with a novel
      homozygous STAT5b mutation.
AB  - CONTEXT: GH insensitivity can be caused by defects in the GH receptor (GHR) or in
      the postreceptor signaling pathway. Recently, two female patients with severe
      growth retardation and pulmonary and immunological problems were described with a
      defect in STAT5b, a critical intermediary of downstream GHR signaling. OBJECTIVE:
      The objective was to determine the functional characteristics of a novel STAT5b
      mutation and describe the phenotype. PATIENT: We describe an adult male patient
      with short stature [-5.9 sd score (SDS)], delayed puberty, and no history of
      pulmonary or immunological problems. GH-binding protein level as well as GH
      secretion characteristics were normal. Plasma prolactin level was elevated.
      Extremely low levels of IGF-I (-6.9 SDS), IGF-binding protein-3 (-12 SDS), and
      acid-labile subunit (-7.5 SDS) were found. RESULTS: We found a homozygous
      frameshift mutation in the STAT5b gene (nucleotide 1102-3insC, Q368fsX376),
      resulting in an inactive truncated protein, lacking most of the DNA binding
      domain and the SH2-domain. CONCLUSIONS: This report confirms the essential role
      of STAT5b in GH signaling in the human. We show for the first time that
      immunological or pulmonary problems or elevated GH secretion are not obligatory
      signs of STAT5b deficiency, whereas hyperprolactinemia appears to be part of the
      syndrome. Therefore, in patients with severe short stature, signs of GH
      insensitivity, and a normal GHR, analysis of the STAT5b gene is recommended.

PMID- 16787987
TI  - Glucagon suppression of ghrelin secretion is exerted at hypothalamus-pituitary
      level.
AB  - CONTEXT: The mechanisms underlying the well-known glucagon-induced satiety effect
      are unclear. Recently, we showed that glucagon induces a remarkable decrease in
      the orexigenic hormone ghrelin that might be responsible for this effect.
      OBJECTIVE: The objective of this study was to evaluate the putative role of the
      hypothalamic pituitary axis in glucagon's suppressive effect on ghrelin
      secretion. DESIGN, SUBJECTS, AND METHODS: Prospectively, we studied the endocrine
      and metabolic responses to im glucagon administration in 22 patients (16 males;
      age, 21-68 yr; body mass index, 28.1 +/- 1.1 kg/m(2)) with a known hypothalamic
      pituitary lesion and at least one pituitary hormone deficiency. Control
      experiments were performed in 27 healthy subjects (15 males; age, 19-65 yr; body
      mass index, 25.5 +/- 0.9 kg/m(2)). RESULTS: The suppression of ghrelin by
      glucagon measured as area under the curve(240 min) was significantly greater in
      controls when compared with patients (P < 0.01). Although there was a significant
      decrease in ghrelin in controls (P < 0.001), ghrelin was almost unchanged in
      patients (P = 0.359). Changes in glucagon, glucose, and insulin levels were
      comparable between both groups. CONCLUSIONS: We show that the hypothalamic
      pituitary axis plays an essential role in the suppression of ghrelin induced by
      im glucagon administration. Glucagon significantly decreases ghrelin levels in
      healthy subjects. However, in the absence of an intact hypothalamic-pituitary
      axis, this effect was abolished. The mechanisms responsible for our observation
      are unlikely to include changes in glucose or insulin levels.

PMID- 16787986
TI  - Effect of gastric bypass and gastric banding on proneurotensin levels in morbidly
      obese patients.
AB  - CONTEXT: Neurotensin is produced mainly in the N cells of the ileum and has a
      role in appetite regulation; levels are decreased in obese subjects and increase
      after bariatric surgery. Mature neurotensin is very unstable, with a short half
      life. OBJECTIVE: The objective of this study was to compare baseline and
      postoperative levels of the more stable neurotensin precursor,
      proneurotensin/neuromedin (pro-NT/NMN), in patients after gastric banding,
      gastric bypass, and nonoperated controls, respectively, during long-term follow
      up. DESIGN AND SETTING: This was a prospective observational study in a
      university hospital. PARTICIPANTS AND MAIN OUTCOME MEASURES: Overnight fasting
      plasma pro-NT/NMN concentrations were measured with a new sandwich immunoassay in
      morbidly obese subjects at baseline and 6, 12, and 24 months after gastric
      banding (n = 8), Roux-en-Y gastric bypass (n = 5), and in nonoperated controls (n
      = 7). RESULTS: After gastric bypass and banding, body weight decreased by (mean
      +/- sd) 29.5 +/- 5.5 and 22.8 +/- 5.9 kg, respectively. The decrease after 3 and
      6 months was more pronounced after gastric bypass compared with gastric banding
      (P < 0.05). Plasma pro-NT/NMN levels in patients after gastric bypass increased
      from 246.3 +/- 174.3 pmol/liter on admission to 748.3 +/- 429.6 pmol/liter after
      24 months (P < 0.01). In contrast, in patients with gastric banding, pro-NT/NMN
      concentrations remained stable (207.3 +/- 60.5 pmol/liter at admission, 226.6 +/-
      116.8 pmol/liter after 24 months). Neither body weight nor plasma pro-NT/NMN
      levels changed in nonoperated controls. CONCLUSION: Plasma pro-NT/NMN levels show
      a more pronounced increase after gastric bypass compared with gastric banding,
      suggesting that specific bariatric surgical procedures result in distinct
      alterations of gastrointestinal hormone metabolism. The more stable precursor pro
      NT/NMN provides a new tool to quantify neurotensin levels in clinical practice.

PMID- 16787988
TI  - The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is
      associated with catalytic activities and cardiovascular disease in Korean men.
AB  - CONTEXT AND OBJECTIVE: It is unclear whether lipoprotein-associated phospholipase
      A(2) (Lp-PLA(2)) exerts a pro- or antiatherogenic effect on cardiovascular
      disease (CVD). We investigated the association between Lp-PLA(2) variant (V279F
      and A379V) and CVD in Korean men. DESIGN: CVD patients (n = 532) and healthy
      controls (n = 670) were genotyped for the Lp-PLA(2) polymorphism (V279F and
      A379V). MAIN OUTCOME MEASURES: We calculated odds ratio (OR) on CVD risk and
      measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle
      size, oxidized LDL, lipid peroxides, and Lp-PLA(2) activity. RESULTS: The
      presence of the 279F allele was associated with a lower risk of CVD [OR 0.646
      (95% confidence interval 0.490-0.850), P = 0.002], and the association still
      remained after adjustments for age, body mass index, waist circumference, waist
      to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95%
      confidence interval 0.512-0.911), P = 0.009]. Lp-PLA(2) activity was lower in CVD
      patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering
      drug (26%), and control subjects (23%) with the V/F genotype, compared with those
      with the V/V genotype. Subjects with the F/F genotype in controls and two CVD
      patients groups showed no appreciable enzymatic activity. Control subjects with
      the V/F genotype had larger LDL particle size than those with the V/V genotype.
      In addition, control subjects carrying the F allele showed lower malondialdehyde
      concentrations. On the other hand, we found no significant relationship between
      A379V genotype and CVD risk. CONCLUSIONS: The association of the F279 loss of
      function variant with the reduced risk of CVD supports the concept that Lp-PLA(2)
      plays a proatherogenic and causative role in CVD.

PMID- 16787989
TI  - Cortisol production rate in posttraumatic stress disorder.
AB  - CONTEXT: Several authors have reported the unsuspected finding of low cortisol
      levels (urinary, salivary, and serum) in patients with posttraumatic stress
      disorder (PTSD). OBJECTIVE: Our objective was to assess concentrations of
      cortisol and its predominant metabolites, cortisol production rate (CPR), and
      glucocorticoid receptor (GR) binding characteristics in PTSD compared with normal
      subjects. DESIGN: Matched PTSD patients and control subjects had CPR determined
      by a stable isotope dilution technique after infusion of deuterated cortisol.
      Serum cortisol, urinary cortisol, and its metabolites were measured by gas
      chromatography/mass spectrometry. GR binding capacity (R(o)) and ligand binding
      affinity (K(d)) were measured in mononuclear leukocytes. SETTING: All subjects
      were tested during a 40-h admission in an inpatient clinical research center.
      PATIENTS AND PARTICIPANTS: Ten patients with PTSD were matched by age and gender
      with 10 controls. OUTCOME MEASURES: Statistical comparison was conducted for
      various measures of cortisol in PTSD patients and normal subjects. RESULTS: No
      statistical difference was found in mean level or circadian pattern of cortisol
      secretion using serum or salivary immunoassay detection methods. Although in the
      normal range, urinary cortisol by immunoassay showed statistically lower values
      over a 24-h period in PTSD patients compared with controls. This finding was not
      confirmed by gas chromatography/mass spectrometry determination of cortisol or
      its metabolites. CPR was not statistically different between these groups. GR
      also showed no alteration in R(o) or K(d) between the groups. CONCLUSION: The
      data indicate that PTSD in the chronic and unprovoked state is not characterized
      by an acute biological stress response.

PMID- 16787990
TI  - Neonatal screening for congenital hypothyroidism based on thyroxine, thyrotropin,
      and thyroxine-binding globulin measurement: potentials and pitfalls.
AB  - CONTEXT: The Dutch T(4)-TSH-TBG-based neonatal screening program detects patients
      with congenital hypothyroidism (CH) of thyroidal (CH-T) as well as central (CH-C)
      origin. The numbers and characteristics of true-positive and false-positive
      referrals will differ from other, predominantly TSH-based, screening methods.
      OBJECTIVE: The present study describes the characteristics of the referred
      neonates, both CH patients and false positives, and of the reported CH patients
      with a false-negative screening result born in the study period. DESIGN, SETTING,
      PATIENTS, AND MAIN OUTCOME MEASURE: For each referred child born between April 1,
      2002, and May 31, 2004, screening results and first venous sample results were
      recorded and classified as transient or permanent CH-T or CH-C or as no CH.
      RESULTS: In the study period, 430,764 children were screened. Of the 772 children
      with abnormal screening results, 224 (29%) had CH; another 13 CH patients did not
      have abnormal screening results, giving an overall CH incidence of 1:1800.
      Incidences of permanent CH, permanent CH-T, permanent CH-C, and transient CH were
      1:2200, 1:2500, 1:21,000, and 1:12,000, respectively. The most frequent
      explanations for the 548 false-positive referrals (71% of the referred cohort)
      were severe illness and TBG deficiency (occurring in 198 and 200 children,
      respectively). CONCLUSIONS: The Dutch incidence figures for CH belong to the
      highest worldwide, suggesting that the T(4)-TSH-TBG screening program is an
      efficient method to detect CH of variable etiology and severity. Still, a small
      percentage of children with CH escaped detection via this screening approach.
      Severe illness and TBG deficiency appear to be responsible for the majority of
      false-positive referrals.

PMID- 16787991
TI  - Quality of life is decreased after treatment for nonfunctioning pituitary
      macroadenoma.
AB  - OBJECTIVE: Although a reduced quality of life (QoL) has been reported after long
      term cure of functioning pituitary adenomas, the effect of successful treatment
      of nonfunctioning pituitary macroadenoma (NFMA) on QoL has not been fully
      addressed. Therefore, we evaluated a broad spectrum of QoL parameters in patients
      successfully treated for NFMA in our center. DESIGN: We conducted a case-control
      study. PATIENTS AND METHODS: We assessed QoL in 99 adult patients (mean age, 61.9
      yr; range, 24-86 yr) in remission during long-term follow-up after surgical (n =
      99) and additional radiotherapeutic (n = 37) treatment for NFMA by four validated
      health-related questionnaires (Hospital Anxiety and Depression Scale,
      Multidimensional Fatigue Index, Nottingham Health Profile, and Short Form-36).
      Patient outcomes were compared with 125 controls and with age-adjusted reference
      values derived from the literature. RESULTS: NFMA patients reported significantly
      impaired QoL in all questionnaires compared with the 125 controls and the age
      adjusted reference values. All subscales of fatigue, assessed using the
      Multidimensional Fatigue Index (general fatigue, physical fatigue, reduction in
      activity, reduction in motivation, and mental fatigue) were impaired. The scores
      in the Nottingham Health Profile pointed toward reduced energy and affected
      emotional reaction. In several subscales of the Short Form-36 (social
      functioning, role limitations due to physical problems, role limitations due to
      emotional problems, and general health perception), NFMA patients reported a
      reduced QoL. CONCLUSION: QoL is considerably reduced in patients after successful
      treatment of NFMA.

PMID- 16787992
TI  - Clinical characterization of familial isolated pituitary adenomas.
AB  - CONTEXT: Familial pituitary adenomas occur rarely in the absence of multiple
      endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). OBJECTIVE: Our
      objective was to characterize the clinical and genealogical features of non
      MEN1/CNC familial isolated pituitary adenomas (FIPA). DESIGN AND SETTING: We
      conducted a retrospective study of clinical and genealogical characteristics of
      FIPA cases and performed a comparison with a sporadic population at 22 university
      hospitals in Belgium, Italy, France, and The Netherlands. RESULTS: Sixty-four
      FIPA families including 138 affected individuals were identified [55
      prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH
      secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree
      relationships predominated (75.6%) among affected individuals. A single tumor
      phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes
      occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases
      (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation
      of multigenerational families. Macroadenomas were more frequent in heterogeneous
      vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous
      families were larger and had more frequent suprasellar extension (P = 0.004) than
      sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma
      cases and within heterogeneous FIPA families; isolated familial somatotropinoma
      cases represented 18% of FIPA cases and were younger at diagnosis than patients
      with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P =
      0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases.
      CONCLUSIONS: Homogeneous and heterogeneous expression of prolactinomas,
      somatotropinomas, NS, and Cushing's disease can occur within families in the
      absence of MEN1/CNC. FIPA and sporadic cases have differing clinical
      characteristics. FIPA may represent a novel endocrine neoplasia classification
      that requires further genetic characterization.

PMID- 16787993
TI  - Comparison of clinical, ultrasonographic, and biochemical differences at the
      beginning of puberty in healthy girls born either small for gestational age or
      appropriate for gestational age: preliminary results.
AB  - CONTEXT: There are limited and controversial data concerning puberty
      characteristics in girls born small for gestational age (SGA). OBJECTIVE: The
      objective of the study was to document clinical, ultrasonographic, and
      biochemical characteristics at the beginning of puberty in matched healthy girls
      born either SGA or appropriate for gestational age (AGA) recruited from the
      community. PATIENTS: Inclusion criteria were breast Tanner stage II and a body
      mass index between the 10th and 95th percentiles. INTERVENTIONS: Recruited
      subjects underwent a complete physical exam, bone age, and ultrasound
      measurements of the internal genitalia. Hormonal assessment included fasting
      early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B,
      FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone.
      Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with
      FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. RESULTS: Sixty
      five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr,
      similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA),
      median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included.
      No differences in the presence of pubic hair, axillary hair, apocrine odor, or
      ultrasound measurements were found. SGA girls had increased baseline E2 as well
      as stimulated E2 and 17OH Prog. CONCLUSIONS: In a preliminary sample of lean,
      healthy girls recruited from the community born either SGA or AGA, we observed
      slight hormonal differences at the beginning of puberty. Longitudinal follow-up
      of this cohort will allow us to understand whether these differences are
      maintained and have a clinical impact in their pubertal development.

PMID- 16787994
TI  - Psychosocial determinants of coronary heart disease in middle-aged women: a
      prospective study in Sweden.
AB  - A social gradient in coronary heart disease (CHD) has been documented in a
      variety of settings, predominantly among men. This study aimed to establish
      whether a social gradient in CHD existed in a group of Swedish women and whether
      it could be explained by established coronary risk factors or psychosocial
      factors. The Women's Lifestyle and Health Cohort Study includes 49,259 women from
      Sweden aged 30-50 years at baseline (1991-1992), when an extensive questionnaire
      was completed. There was complete follow-up through linkages to national
      registries until the end of 2002, during which time 210 cases of incident fatal
      CHD or nonfatal myocardial infarction occurred. Risk of CHD was significantly
      inversely related to years of education, the socioeconomic status proxy (hazard
      ratio comparing the lowest with the highest education group = 3.3, 95% confidence
      interval: 2.2, 4.7). This association was reduced after adjustment for
      established coronary risk factors (smoking, body mass index, alcohol consumption,
      diabetes, hypertension, exercise; hazard ratio = 1.9, 95% confidence interval:
      1.3, 2.8). Job strain and social support were weakly related to CHD and did not
      explain the gradient by years of education. Self-rated health was strongly
      related to CHD, mediated by established coronary risk factors. Results show a
      strong gradient in CHD by years of education explained by established coronary
      risk factors but not by job strain or social support.

PMID- 16787995
TI  - PLASQ: a generalized linear model-based procedure to determine allelic dosage in
      cancer cells from SNP array data.
AB  - Human cancer is largely driven by the acquisition of mutations. One class of such
      mutations is copy number polymorphisms, comprised of deviations from the normal
      diploid two copies of each autosomal chromosome per cell. We describe a probe
      level allele-specific quantitation (PLASQ) procedure to determine copy number
      contributions from each of the parental chromosomes in cancer cells from single
      nucleotide polymorphism (SNP) microarray data. Our approach is based upon a
      generalized linear model that takes advantage of a novel classification of probes
      on the array. As a result of this classification, we are able to fit the model to
      the data using an expectation-maximization algorithm designed for the purpose. We
      demonstrate a strong model fit to data from a variety of cell types. In normal
      diploid samples, PLASQ is able to genotype with very high accuracy. Moreover, we
      are able to provide a generalized genotype in cancer samples (e.g. CCCCT at an
      amplified SNP). Our approach is illustrated on a variety of lung cancer cell
      lines and tumors, and a number of events are validated by independent
      computational and experimental means. An R software package containing the
      methods is freely available.

PMID- 16787996
TI  - Adaptive design: estimation and inference with censored data in a semiparametric
      model.
AB  - In this article, we provide a method of estimation for the treatment effect in
      the adaptive design for censored survival data with or without adjusting for risk
      factors other than the treatment indicator. Within the semiparametric Cox
      proportional hazards model, we propose a bias-adjusted parameter estimator for
      the treatment coefficient and its asymptotic confidence interval at the end of
      the trial. The method for obtaining an asymptotic confidence interval and point
      estimator is based on a general distribution property of the final test statistic
      from the weighted linear rank statistics at the interims with or without
      considering the nuisance covariates. The computation of the estimates is
      straightforward. Extensive simulation studies show that the asymptotic confidence
      intervals have reasonable nominal probability of coverage, and the proposed point
      estimators are nearly unbiased with practical sample sizes.

PMID- 16787997
TI  - A marginalized pattern-mixture model for longitudinal binary data when
      nonresponse depends on unobserved responses.
AB  - This paper proposes a method for modeling longitudinal binary data when
      nonresponse depends on unobserved responses. The proposed method presumes that
      the target of inference is the marginal distribution of the response at each
      occasion and its dependence on covariates, and can accommodate both monotone and
      non-monotone missingness. The approach involves a marginally specified pattern
      mixture model that directly parameterizes both the marginal means at each
      occasion and the dependence of each response on indicators of nonresponse
      pattern. This formulation readily incorporates a variety of nonresponse processes
      assumed within a sensitivity analysis. Once identifying restrictions have been
      made, estimation of model parameters proceeds via solution to a set of modified
      generalized estimating equations. The proposed method provides an alternative to
      standard selection and pattern-mixture modeling frameworks, while featuring
      certain advantages of each. The paper concludes with application of the method to
      data from a contraceptive clinical trial with substantial dropout.

PMID- 16787998
TI  - Assessing site-interdependent phylogenetic models of sequence evolution.
AB  - In recent works, methods have been proposed for applying phylogenetic models that
      allow for a general interdependence between the amino acid positions of a
      protein. As of yet, such models have focused on site interdependencies resulting
      from sequence-structure compatibility constraints, using simplified structural
      representations in combination with a set of statistical potentials. This
      structural compatibility criterion is meant as a proxy for sequence fitness, and
      the methods developed thus far can incorporate different site-interdependent
      fitness proxies based on other measurements. However, no methods have been
      proposed for comparing and evaluating the adequacy of alternative fitness proxies
      in this context, or for more general comparisons with canonical models of protein
      evolution. In the present work, we apply Bayesian methods of model selection
      based on numerical calculations of marginal likelihoods and posterior predictive
      checks-to evaluate models encompassing the site-interdependent framework. Our
      application of these methods indicates that considering site-interdependencies,
      as done here, leads to an improved model fit for all data sets studied. Yet, we
      find that the use of pairwise contact potentials alone does not suitably account
      for across-site rate heterogeneity or amino acid exchange propensities; for such
      complexities, site-independent treatments are still called for. The most favored
      models combine the use of statistical potentials with a suitably rich site
      independent model. Altogether, the methodology employed here should allow for a
      more rigorous and systematic exploration of different ways of modeling explicit
      structural constraints, or any other site-interdependent criterion, while best
      exploiting the richness of previously proposed models.

PMID- 16787999
TI  - Methoxychlor induces atresia of antral follicles in ERalpha-overexpressing mice.
AB  - Methoxychlor (MXC) is a pesticide that is known to bind to estrogen receptor
      alpha (ERalpha) and to induce atresia of antral ovarian follicles. Although
      studies have shown that MXC is toxic to the ovary, we hypothesize that
      perturbation to the estrogen-signaling system (i.e., increase or decrease in
      estrogen sensitivity) might alter ovarian responsiveness to MXC. Thus, we
      examined whether ERalpha overexpression alters the ability of MXC to increase
      follicle atresia. To do so, we employed a transgenic mouse model in which ERalpha
      can be inducibly overexpressed in animal tissues (ERalpha overexpressors). We
      dosed female controls and ERalpha overexpressors with sesame oil (vehicle
      control) or MXC (32 and 64 mg/kg/day) for 20 days. After dosing, the ovaries were
      collected for histological evaluation of follicle numbers and follicle atresia,
      while blood was collected for measurements of hormones. Estrous cycles were
      determined in all animals to ensure that all were terminated during estrus.
      Although there were no significant effects of MXC on the numbers of primordial,
      primary, and preantral follicles in both controls and ERalpha overexpressors,
      there was an effect on antral follicles. Specifically, our data indicate that 32
      and 64 mg/kg MXC increased the percentage of atretic follicles compared to
      vehicle in both control and ERalpha overexpressor groups. Moreover, there was a
      clear trend toward greater sensitivity to 64 mg/kg MXC in ERalpha-overexpressing
      mice compared to control animals. Specifically, at the 64-mg/kg MXC dose, ERalpha
      overexpressing mice had a significantly higher percentage of atretic follicles
      compared to control animals (controls = 21.5 +/- 3%, n = 5; ERalpha
      overexpressors = 37 +/- 23%, n = 9, p < or = 0.05 vs. controls). After 20 days of
      dosing, there were no differences in estradiol levels between controls and
      ERalpha-overexpressing mice in all treatment groups. Follicle-stimulating hormone
      (FSH) levels were similar in sesame oil-treated control mice and control mice
      treated with 32 mg/kg MXC, while control mice treated with 64 mg/kg MXC had
      significantly lower levels of FSH compared to sesame oil-treated controls (sesame
      oil = 4.31 +/- 0.7, MXC [64 mg/kg/day] = 1.89 +/- 0.4, n = 3, p < or = 0.02 vs.
      sesame oil). ERalpha-overexpressing mice treated with sesame oil, 32 or 64 mg/kg
      MXC, had similar FSH levels. Thus, we observed an increased percentage of atretic
      antral follicles in ERalpha-overexpressing mice treated with MXC compared to
      control mice treated with the same compound, suggesting that the ERalpha
      signaling pathway plays an important role in MXC-induced atresia. The trend
      toward greater sensitivity to MXC in ERalpha-overexpressing mice compared to
      control animals cannot be explained by alterations in estradiol and/or FSH
      levels.

PMID- 16788000
TI  - Evidence for a novel endocrine disruptor: the pesticide propanil requires the
      ovaries and steroid synthesis to enhance humoral immunity.
AB  - Steroid hormones are known to affect the humoral immune response to a variety of
      antigens. However, the mechanisms regulating these effects are poorly understood.
      The immunotoxic chemical propanil and estrogen have similar effects on the immune
      system including augmentation of humoral immune responses. Propanil enhances the
      number of phosphorylcholine (PC)-specific IgG2b, IgG3, and IgM antibody-secreting
      cells (ASCs) in the spleen four- to sixfold 7 days after vaccination of female
      C57BL/6 mice with heat-killed Streptococcus pneumoniae. Several experiments were
      performed to test the hypothesis that propanil increases the response via an
      estrogenic pathway. Ovariectomy abrogated the effect of propanil on the PC
      specific ASC response. Both in vitro and in vivo assays indicate that propanil
      does not bind either estrogen receptor (ER) alpha or beta. Exogenous estradiol
      administration in ovariectomized mice failed to restore the effect of propanil on
      the PC response. Treatment of female mice with a pure ER antagonist, ICI 182,780,
      or the progesterone antagonist RU486 did not inhibit the increase in ASCs. These
      data suggest that estrogen and progesterone do not regulate the effect of
      propanil. However, complete inhibition of steroid synthesis with the gonadotropin
      releasing hormone (GnRH) antagonist antide abrogated the increased response in
      propanil-treated mice, indicating a necessary role for steroid synthesis.
      Experiments in male mice demonstrated that propanil increased the number of ASCs
      comparable to female mice. However, orchiectomy did not inhibit this effect,
      suggesting that androgens do not regulate the amplification of the humoral
      response. These data suggest a novel role for the ovarian hormones in the
      regulation of the PC-specific antibody response.

PMID- 16788001
TI  - Baseline MRI delivery characteristics predict change in invasive ductal breast
      carcinoma PET metabolism as a result of primary chemotherapy administration.
AB  - BACKGROUND: The aim of the study was to investigate whether pre-therapy vascular
      delivery assessment [using dynamic contrast enhanced magnetic resonance imaging
      (DCE-MRI)] can predict reduction in breast cancer metabolism [detected using 2
      [(18)F] fluoro-2-deoxy-D-glucose positron emission tomography ((18)F(-)FDG-PET)]
      after a single cycle of chemotherapy. Reduction in (18)F-FDG PET metabolism has
      previously been shown to correlate with histological response to primary
      chemotherapy. PATIENTS AND METHODS: Seventeen patients with large or locally
      advanced invasive ductal carcinomas of the breast were imaged using DCE-MRI and
      (18)F-FDG-PET prior to therapy and 20 days after the first cycle of chemotherapy.
      MRI data were analysed using a multi-compartment model. PET data were analysed
      using standardised uptake value (SUV) analysis. RESULTS: A significant
      association (P <0.05) was observed between pre-therapy DCE-MRI vascular
      parameters and the reduction in PET metabolism resulting from administration of
      one cycle of chemotherapy. CONCLUSIONS: A relationship was demonstrated between
      pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism after
      a single cycle of chemotherapy. This suggests that reduction in PET metabolism as
      a result of chemotherapy may be dependent, at least in part, on pre-therapy
      vascular delivery. These pre-therapy vascular characteristics may be suitable for
      use as a surrogate measure for initial chemotherapy delivery, a key factor in
      chemotherapeutic efficacy.

PMID- 16788002
TI  - Mast cells in Waldenstrom's macroglobulinemia support lymphoplasmacytic cell
      growth through CD154/CD40 signaling.
AB  - Bone marrow (BM) mast cells (MC) are commonly found in association with
      lymphoplasmacytic cells (LPC) in patients with Waldenstrom's macroglobulinemia
      (WM). We therefore sought to clarify the role of MC in WM. Co-culture of
      sublethally irradiated HMC-1 MC, KU812 basophilic cells, or autologous BM MC
      along with BM LPC from WM patients resulted in MC dose-dependent tumor colony
      formation and/or proliferation as assessed by 3H-thymidine uptake studies.
      Furthermore, by immunohistochemistry, multicolor flow cytometry and/or RT-PCR
      analysis, CD40 ligand (CD154), a potent inducer of B-cell expansion, was
      expressed on BM MC from 32 of 34 (94%), 11 of 13 (85%), and 7 of 9 (78%)
      patients, respectively. In contrast, MC from five healthy donors did not express
      CD154. By multicolor flow cytometry, CD154 was expressed on BM LPC from 35 of 38
      (92%) patients and functionality was confirmed by CD154 and CD40 agonistic
      antibody stimulation, which induced proliferation, support survival and/or pERK
      phosphorylation of LPC. Moreover, MC induced expansion of LPC from 3 of 5
      patients was blocked in a dose dependent manner by use of a CD154 blocking
      protein. These studies demonstrate that in WM, MC may support tumor cell
      expansion through constitutive CD154-CD40 signaling and therefore provide the
      framework for therapeutic targeting of MC and MC-WM cell interactions in WM.

PMID- 16788003
TI  - A phase II trial of neoadjuvant cisplatin-fluorouracil followed by postoperative
      intraperitoneal floxuridine-leucovorin in patients with locally advanced gastric
      cancer.
AB  - BACKGROUND: The aim of the study was to evaluate the efficacy and toxicity of
      neoadjuvant chemotherapy with intravenous (i.v.) cisplatin and fluorouracil (5
      FU), surgery and postoperative intraperitoneal (i.p.) floxuridine (FUdR) and
      leucovorin (LV) in patients with locally advanced gastric cancer. PATIENTS AND
      METHODS: Preoperative staging was confirmed by laparoscopy (LAP). Two cycles of
      i.v. cisplatin (20 mg/m(2)/day, rapid infusion) and 5-FU (1000 mg/m(2),
      continuous 24-h infusion), given on days 1-5 and 29-34, were followed by a
      radical gastrectomy and a D2 lymphadenectomy. Patients having R0 resections were
      to receive three cycles of i.p. FUdR (1000 mg/m(2)) and LV (240 mg/m(2)), given
      on days 1-3, 15-17 and 29-31. Intraperitoneal chemotherapy was begun 5-10 days
      from surgery. RESULTS: Thirty-eight patients were treated. Both preoperative and
      postoperative chemotherapy were well tolerated. T stage downstaging (pretreatment
      LAP versus surgical pathological stage) was seen in 23% of patients. The R0
      resection rate was 84%. Neither an increase in postoperative morbidity nor
      operative mortality was noted. With a median follow-up of 43.0 months, 15
      patients (39.5%) are still alive (median survival 30.3 months). Good pathologic
      response, seen in five patients (15%), was associated with better survival (P =
      0.053). Peritoneal and hepatic failures were found in 22% and 9% of patients,
      respectively. Quality of life seemed to be preserved. CONCLUSIONS: Neoadjuvant
      cisplatin/5-FU followed by postoperative i.p. FUdR/LV can be safely delivered to
      patients undergoing radical gastrectomy and D2 lymphadenectomy. The R0 resection
      and the survival rates are encouraging. An association between pathologic
      response and patient outcome was suggested.

PMID- 16788004
TI  - ACE2 gene transfer attenuates hypertension-linked pathophysiological changes in
      the SHR.
AB  - Recently discovered, angiotensin-converting enzyme-2 (ACE2) is an important
      therapeutic target in the control of cardiovascular diseases as a result of its
      proposed central role in the control of angiotensin peptides. Thus our objective
      in the present study was to determine whether ACE2 gene transfer could decrease
      high blood pressure (BP) and would improve cardiac dysfunctions induced by
      hypertension in the spontaneously hypertensive rat (SHR) model. Five-day-old SHR
      and normotensive WKY rats received a single intracardiac bolus injection of
      lentiviral vector containing either murine ACE2 (ACE2) or control enhanced green
      fluorescent protein (EGFP) genes. Systolic BP, cardiac functions, and
      perivascular fibrosis were evaluated 4 mo after ACE2 gene transduction. ACE2 gene
      transfer resulted in a significant attenuation of high BP in the SHR (149 +/- 2
      mmHg in lenti-ACE2 vs. 180 +/- 9 mmHg in lenti-EGFP, P < 0.01). In contrast, no
      significant effect of lenti-ACE2 on BP of WKY rats was observed. Lenti-ACE2
      treated SHR showed an 18% reduction in left ventricular wall thickness (1.52 +/-
      0.04 vs. 1.86 +/- 0.04 mm in lenti-EGFP, P < 0.01). In addition, there was a 12%
      increase in left ventricular end diastolic and a 21% increase in end systolic
      diameters in lenti-ACE2-treated SHR. Finally, lenti-ACE2 treatment resulted in a
      significant attenuation of perivascular fibrosis in the SHR. In contrast, ACE2
      gene transfer did not influence any of these parameters in WKY rats. These
      observations demonstrate that ACE2 overexpression exerts protective effects on
      high BP and cardiac pathophysiology induced by hypertension in the SHR.

PMID- 16788005
TI  - Identification of estrogen-responsive genes in the parenchyma and fat pad of the
      bovine mammary gland by microarray analysis.
AB  - Identification of estrogen-responsive genes is an essential step toward
      understanding mechanisms of estrogen action during mammary gland development. To
      identify these genes, 16 prepubertal heifers were used in a 2 x 2 factorial
      experiment, with ovarian status (intact or ovariectomized) as the first factor
      and estrogen treatment as the second (control or estradiol). Heifers were
      ovariectomized at approximately 4.5 mo of age, and estrogen treatments were
      initiated 1 mo later. After 3 days of treatment, gene expression was analyzed in
      the parenchyma and fat pad of the bovine mammary gland using a high-density
      oligonucleotide microarray. Oligonucelotide probes represented 40,808 tentative
      consensus sequences from TIGR Bos taurus Gene Index and 4,575 singleton expressed
      sequence tags derived from libraries of pooled mammary gland and gut tissues.
      Microarray data were analyzed by use of the SAS mixed procedure, with an
      experiment-wide permutation-based significance level of P < 0.1. Considerable
      differences in basal gene expression were noted between mammary parenchyma and
      fat pad. A total of 124 estrogen-responsive genes were identified, with most
      responding only in the parenchyma or the fat pad. The majority of genes
      identified were not previously reported to be estrogen responsive. These
      undoubtedly include genes that are regulated indirectly but also include known
      estrogen-targeted genes and novel genes with potential estrogen-responsive
      elements in their promoter regions. The distinctive expression patterns regulated
      by estrogen in parenchyma and fat pad shed light on the need for both tissues to
      obtain normal mammary development.

PMID- 16788006
TI  - Differential expression profiling of the blind subterranean mole rat Spalax
      ehrenbergi superspecies: bioprospecting for hypoxia tolerance.
AB  - The blind subterranean mole rat of the Spalax ehrenbergi superspecies, living
      underground and exposed to fluctuating oxygen and carbon dioxide levels, is an
      excellent model of hypoxic tolerance. Unique structural and functional
      adaptations of the cardiovascular and respiratory systems allow these underground
      mammals to survive at severely reduced oxygen tension. Elucidation of the natural
      variation and evolutionary changes under hypoxia within this superspecies may
      have biomedical applications in ischemic syndromes and cancer. In this study, we
      have compared expression profiles of muscle tissue at normoxic (21%) and hypoxic
      (3%) levels of oxygen concentration between two allospecies of the S. ehrenbergi
      superspecies exhibiting differential hypoxia tolerance in accordance with their
      ecological regimes. Profiling was performed by cross-species hybridization using
      a mouse cDNA array containing 15,000 gene elements. Results uncover species
      specific responses to hypoxic stress among numerous genes involved in
      angiogenesis, apoptosis, and oxidative stress management. Among the most striking
      results are differential expressions of cardiac ankyrin repeat protein (Carp),
      activating transcription factor 3 (Atf3), LIM and cysteine-rich domains 1
      (Lmcd1), cysteine and glycine-rich protein 2 (Csrp2), and ras homolog gene
      family, member B (RhoB). These findings support the hypothesis that allospecies
      of the S. ehrenbergi superspecies are variably adapted to fluctuating oxygen
      tension. Differences may involve specific metabolic pathways and functional
      adaptations at the structural and molecular levels.

PMID- 16788008
TI  - Differential effects of hypertension in the aetiology of major intracerebral
      haemorrhage subtypes.

PMID- 16788007
TI  - Carotid sinus hypersensitivity: an age-related phenomenon.

PMID- 16788009
TI  - Inheritance pattern of familial moyamoya disease: autosomal dominant mode and
      genomic imprinting.
AB  - BACKGROUND: Although the aetiology of moyamoya disease (MMD) has not been fully
      clarified, genetic analysis of familial MMD (F-MMD) has considerable potential to
      disclose it. OBJECTIVE: To determine the inheritance pattern and clinical
      characteristics of F-MMD to enable precise genetic analyses of the disease.
      METHODS: 15 highly aggregated Japanese families (52 patients; 38 women and 14
      men) with three or more affected members were examined. The difference in
      categories of age at onset (child onset, adult onset and asymptomatic) between
      paternal and maternal transmission was compared by chi2 statistics. RESULTS: In
      all families there had been three or more generations without consanguinity, and
      all types of transmission, including father-to-son, were observed. Among a total
      of 135 offspring of affected people, 59 (43.7%) were patients with MMD or
      obligatory carriers. Affected mothers were more likely to produce late-onset
      (adult-onset or asymptomatic) female offspring (p = 0.007). CONCLUSIONS: The mode
      of inheritance of F-MMD is autosomal dominant with incomplete penetrance. Thus,
      in future genetic studies on F-MMD, parametric linkage analyses using large
      families with an autosomal dominant mode of inheritance are recommended. Genomic
      imprinting may be associated with the disease.

PMID- 16788010
TI  - Charcot-Marie-Tooth disease type 1A duplication with severe paresis of the
      proximal lower limb muscles: a long-term follow-up study.
AB  - OBJECTIVE: To describe a large pedigree with Charcot-Marie-Tooth disease type 1A
      (CMT1A) duplication in which severe pelvic and thigh musculature weakness
      occurred in two patients, detected by analysing the leg muscle atrophy pattern on
      magnetic resonance imaging (MRI). METHODS: The pedigree comprised 18 patients,
      aged between 15 and 85 (median 46) years, who were serially evaluated for up to
      three decades. All 18 patients and 13 non-affected at-risk people underwent
      electrophysiological examination. An MRI study of lower limb musculature was
      carried out in four patients. Three patients underwent sural-nerve biopsy.
      Genetic testing was carried out in 17 patients and in all 13 at-risk normal
      people. RESULTS: Fourteen patients were asymptomatic or slightly disabled. The
      two oldest patients, aged 84 and 80, showed a moderate phenotype. Two other
      patients, aged 70 and 53, showed late-onset and gradually progressive peroneal
      paresis extending up to the thigh and pelvic musculature, resulting in waddling
      gait. MRI scans of all three patients with a mild phenotype showed subtle and
      subclinical fatty infiltration of calf anterolateral muscle compartments, with
      thigh muscle involvement in one patient, and extensive atrophy of intrinsic foot
      muscles. In the youngest patient with proximal leg weakness, the MRI scan showed
      massive fatty atrophy of all the calf muscles, posteromedial thigh muscle
      compartments, and internal and external hip rotator muscles. Sural-nerve biopsy
      specimens showed hypertrophic neuropathy with no superimposed inflammation. Good
      correlation was seen between electrophysiological and genetic testing.
      CONCLUSIONS: Late in the clinical course, a small proportion of patients with
      CMT1A develop severe proximal leg weakness, and long-term follow-up is essential
      for its detection. MRI scans may show subclinical involvement of the thigh
      musculature.

PMID- 16788011
TI  - Is the frequency of abnormalities on magnetic resonance imaging in isolated optic
      neuritis related to the prevalence of multiple sclerosis? A global comparison.
AB  - The link between optic neuritis and multiple sclerosis is well established, as is
      the increased risk of conversion to multiple sclerosis, with lesions seen at
      presentation on the magnetic resonance imaging (MRI) scan of the brain. One or
      more asymptomatic lesions were present in 77% of the optic neuritis cohort from
      London, UK, a higher proportion than that reported in other large cohorts studied
      elsewhere, where generally lower prevalence rates for multiple sclerosis are also
      reported. These observations may support the hypothesis that optic neuritis is
      more likely to be associated with abnormalities on MRI and to be due to multiple
      sclerosis in geographical regions where multiple sclerosis is more common.

PMID- 16788012
TI  - Cardiovascular and metabolic changes in insular infarcts: a delayed phenomenon?

PMID- 16788013
TI  - Neurological pictures. Massage of a giant retroperitoneal neurofibroma.

PMID- 16788014
TI  - Neurological pictures. Hypomelanosis of Ito.

PMID- 16788015
TI  - Frail elderly patients with dementia go too fast.
AB  - The reason why patients with dementia fall more often and sustain more fractures
      than patients without dementia remains unclear. Therefore, the relationship
      between dementia and gait velocity as a marker for mobility and falls in a cohort
      of frail elderly (mean age of 77.3 years) inpatients was assessed. Patients with
      dementia were expected to walk slower than patients without dementia. A trend was
      indeed observed: absolute gait velocity of 0.59 m/s in patients with dementia (n
      = 63) versus 0.65 m/s in patients without dementia (n = 62; p = 0.19). After
      adjustment for parkinsonism and walking aids, however, patients with dementia
      walked 0.44 m/s faster than patients without dementia (p = 0.02). Probable
      explanations are frontal lobe disinhibition and lack of insight, causing patients
      with dementia to walk relatively too fast in the context of their frailty.
      Therefore, the high risk of falls in dementia may be partially explained by the
      loss of control of gait velocity.

PMID- 16788016
TI  - James Collier (1870-1935) and uncal herniation.

PMID- 16788017
TI  - Insular cortical ischaemia does not independently predict acute hypertension or
      hyperglycaemia within 3 h of onset.
AB  - OBJECTIVES: To test the hypothesis that insular cortical ischaemia is associated
      with acute hypertension and hyperglycaemia. METHODS: From the Canadian Activase
      for Stroke Effectiveness Study, which included only patients treated with
      thrombolysis hyperacutely (ie, within 3 h of onset of stroke), 966 patients were
      identified with ischaemia affecting (n = 685), or sparing (n = 281), the insular
      cortex. Demographic and clinical data, pretreatment indices of blood pressure,
      blood glucose, atrial fibrillation, and clinical imaging and outcome measures
      were compared between the two groups. Multivariable linear regression was used to
      assess predictors of systolic blood pressure and glucose levels before
      thrombolysis. RESULTS: Pretreatment hypertension (p = 0.009), but not
      hyperglycaemia (p = 0.32), was predicted by insular ischaemia in univariable
      linear regression analyses. After adjusting for other factors, however, insular
      cortical ischaemia was not found to be an independent predictor for acute
      hypertension or hyperglycaemia. CONCLUSIONS: Raised blood pressure or serum
      glucose levels in hyperacute (<3 h) cerebral ischaemia is not independently
      predicted by insular involvement. Several hours are required for sympathetic
      manifestations of insular ischaemia to evolve.

PMID- 16788018
TI  - Internal carotid artery vasospasm syndrome: demonstration by neuroimaging.

PMID- 16788019
TI  - Adult onset leucoencephalopathy with brain stem and spinal cord involvement and
      normal lactate.

PMID- 16788020
TI  - The LRRK2 gene in Parkinson's disease: mutation screening in patients from
      Germany.

PMID- 16788022
TI  - Partitioning locomotor energy use among and within muscles. Muscle blood flow as
      a measure of muscle oxygen consumption.
AB  - Linking the mechanics and energetics of locomotion in vertebrates has been
      hampered by a lack of information regarding the energy use of individual skeletal
      muscles in vivo. Here, we present a review of the available data concerning the
      relationship between the rates of skeletal muscle blood flow and oxygen
      consumption (V(O2)). In active muscle, during aerobically supported exercise,
      there is a linear relationship between these variables, irrespective of the
      muscle fiber type and intensity of exercise through most of the aerobic exercise
      range. We conclude that the rate of blood flow is the best available indicator of
      aerobic metabolic rate in multiple individual muscles or regions of muscles
      during locomotion. The practical considerations of using the injectable
      microsphere technique to measure muscle blood flow in this context are discussed.

PMID- 16788023
TI  - The cost of running uphill: linking organismal and muscle energy use in guinea
      fowl (Numida meleagris).
AB  - Uphill running requires more energy than level running at the same speed, largely
      due to the additional mechanical work of elevating the body weight. We explored
      the distribution of energy use among the leg muscles of guinea fowl running on
      the level and uphill using both organismal energy expenditure (oxygen
      consumption) and muscle blood flow measurements. We tested each bird under four
      conditions: (1) rest, (2) a moderate-speed level run at 1.5 m s(-1), (3) an
      incline run at 1.5 m s(-1) with a 15% gradient and (4) a fast level run at a
      speed eliciting the same metabolic rate as did running at a 15% gradient at 1.5 m
      s(-1) (2.28-2.39 m s(-1)). The organismal energy expenditure increased by 30%
      between the moderate-speed level run and both the fast level run and the incline
      run, and was matched by a proportional increase in total blood flow to the leg
      muscles. We found that blood flow increased significantly to nearly all the leg
      muscles between the moderate-speed level run and the incline run. However, the
      increase in flow was distributed unevenly across the leg muscles, with just three
      muscles being responsible for over 50% of the total increase in blood flow during
      uphill running. Three muscles showed significant increases in blood flow with
      increased incline but not with an increase in speed. Increasing the volume of
      active muscle may explain why in a previous study a higher maximal rate of oxygen
      consumption was measured during uphill running. The majority of the increase in
      energy expenditure between level and incline running was used in stance-phase
      muscles. Proximal stance-phase extensor muscles with parallel fibers and short
      tendons, which have been considered particularly well suited for doing positive
      work on the center of mass, increased their mass-specific energy use during
      uphill running significantly more than pinnate stance-phase muscles. This finding
      provides some evidence for a division of labor among muscles used for mechanical
      work production based on their muscle-tendon architecture. Nevertheless, 33% of
      the total increase in energy use (40% of the increase in stance-phase energy use)
      during uphill running was provided by pinnate stance-phase muscles. Swing-phase
      muscles also increase their energy expenditure during uphill running, although to
      a lesser extent than that required by running faster on the level. These results
      suggest that neither muscle-tendon nor musculoskeletal architecture appear to
      greatly restrict the ability of muscles to do work during locomotor tasks such as
      uphill running, and that the added energy cost of running uphill is not solely
      due to lifting the body center of mass.

PMID- 16788024
TI  - Hot limpets: predicting body temperature in a conductance-mediated thermal
      system.
AB  - Living at the interface between the marine and terrestrial environments,
      intertidal organisms may serve as a bellwether for environmental change and a
      test of our ability to predict its biological consequences. However, current
      models do not allow us to predict the body temperature of intertidal organisms
      whose heat budgets are strongly affected by conduction to and from the
      substratum. Here, we propose a simple heat-budget model of one such animal, the
      limpet Lottia gigantea, and test the model against measurements made in the
      field. Working solely from easily measured physical and meteorological inputs,
      the model predicts the daily maximal body temperatures of live limpets within a
      fraction of a degree, suggesting that it may be a useful tool for exploring the
      thermal biology of limpets and for predicting effects of climate change. The
      model can easily be adapted to predict the temperatures of chitons, acorn
      barnacles, keyhole limpets, and encrusting animals and plants.

PMID- 16788025
TI  - Thermal stress on intertidal limpets: long-term hindcasts and lethal limits.
AB  - When coupled with long-term meteorological records, a heat-budget model for the
      limpet, Lottia gigantea, provides a wealth of information regarding environmental
      and topographic controls of body temperature in this ecologically important
      species. (1) The maximum body temperature predicted for any site (37.5 degrees C)
      is insufficient to kill all limpets, suggesting that acute thermal stress does
      not set an absolute upper limit to the elevation of L. gigantea on the shore.
      Therefore, the upper limit must be set by behavioral responses, sublethal effects
      or ecological interactions. (2) Temperatures sufficient to kill limpets are
      reached at only a small fraction of substratum orientations and elevations and on
      only three occasions in 5 years. These rare predicted lethal temperatures could
      easily be missed in field measurements, thereby influencing the interpretation of
      thermal stress. (3) Body temperature is typically higher than air temperature,
      but maximum air temperature can nonetheless be used as an accurate predictor of
      maximum body temperature. Warmer air temperatures in the future may thus cause
      increased mortality in this intertidal species. Interpretation of the ecological
      effects of elevated body temperature depends strongly on laboratory measurements
      of thermal stress, highlighting the need for additional research on the temporal
      and spatial variability of thermal limits and sublethal stress. The lengthy time
      series of body temperatures calculated from the heat-budget model provides
      insight into how these physiological measurements should be conducted.

PMID- 16788026
TI  - Somite formation and expression of MyoD, myogenin and myosin in Atlantic halibut
      (Hippoglossus hippoglossus L.) embryos incubated at different temperatures:
      transient asymmetric expression of MyoD.
AB  - Genes encoding the myogenic regulating factors MyoD and myogenin and the
      structural muscle proteins myosin light chain 2 (MyLC2) and myosin heavy chain
      (MyHC) were isolated from juvenile Atlantic halibut (Hippoglossus hippoglossus
      L.). The impact of temperature on their temporal and spatial expression during
      somitogenesis were examined by incubating halibut embryos at 4, 6 and 8 degrees
      C, and regularly sampling for whole-mount in situ hybridisation and reverse
      transcription (RT)-PCR. There were no significant effects of temperature on the
      onset of somitogenesis or number of somites at hatching. The rate of somite
      formation increased with increasing temperature, and the expression of MyoD,
      myogenin and MyHC followed the cranial-to-caudal somite formation. Hence, no
      significant effect of temperature on the spatial and temporal expression of the
      genes studied was found in relation to somite stage. MyoD, which has subsequently
      been shown to encode the MyoD2 isoform, displayed a novel bilaterally asymmetric
      expression pattern only in white muscle precursor cells during early halibut
      somitogenesis. The expression of myogenin resembled that previously described for
      other fish species, and preceded the MyHC expression by approximately five
      somites. Two MyLC2 cDNA sequences were for the first time described for a
      flatfish, probably representing embryonic (MyLC2a) and larval/juvenile (MyLC2b)
      isoforms. Factors regulating muscle determination, differentiation and
      development have so far mostly been studied in vertebrates with external
      bilateral symmetry. The findings of the present study suggest that more such
      investigations of flatfish species could provide valuable information on how
      muscle-regulating mechanisms work in species with different anatomical,
      physiological and ecological traits.

PMID- 16788028
TI  - Silken toolkits: biomechanics of silk fibers spun by the orb web spider Argiope
      argentata (Fabricius 1775).
AB  - Orb-weaving spiders spin five fibrous silks from differentiated glands that
      contain unique sets of proteins. Despite diverse ecological functions, the
      mechanical properties of most of these silks are not well characterized. Here, we
      quantify the mechanical performance of this toolkit of silks for the silver
      garden spider Argiope argentata. Four silks exhibit viscoelastic behaviour
      typical of polymers, but differ statistically from each other by up to 250% in
      performance, giving each silk a distinctive suite of material properties. Major
      ampullate silk is 50% stronger than other fibers, but also less extensible.
      Aciniform silk is almost twice as tough as other silks because of high strength
      and extensibility. Capture spiral silk, coated with aqueous glue, is an order of
      magnitude stretchier than other silks. Dynamic mechanical properties are
      qualitatively similar, but quantitatively vary by up to 300% among silks. Storage
      moduli are initially nearly constant and increase after fiber yield, whereas loss
      tangents reach maxima of 0.1-0.2 at the yield. The remarkable mechanical
      diversity of Argiope argentata silks probably results in part from the different
      molecular structures of fibers and can be related to the specific ecological role
      of each silk. Our study indicates substantial potential to customize the
      mechanics of bioengineered silks.

PMID- 16788027
TI  - The role of adrenergic stimulation in maintaining maximum cardiac performance in
      rainbow trout (Oncorhynchus mykiss) during hypoxia, hyperkalemia and acidosis at
      10 degrees C.
AB  - As rainbow trout approach exhaustion during prolonged exercise, they maintain
      maximum cardiac output despite the fact their venous blood, which bathes the
      heart, becomes hypoxic, acidotic and hyperkalemic. Because these factors are
      individually recognized to have detrimental inotropic and chronotropic effects on
      cardiac performance, we hypothesized that adrenergic stimulation is critical in
      maintaining maximum cardiac performance under these collectively adverse
      conditions in vivo. To test this hypothesis, maximum cardiac performance in the
      presence and absence of maximal adrenergic stimulation was assessed with in situ
      rainbow trout hearts using relevant hyperkalemic (5.0 mmol l(-1) K+), acidotic
      (pH 7.5) and hypoxic challenges. With tonic adrenergic stimulation (5.0 nmol l(
      1) adrenaline), hearts produced only 44.8+/-14.6% of their normal maximum cardiac
      output when exposed under normoxic conditions (20 kPa) to the hyperkalemic,
      acidotic perfusate, indicating that in vivo there was no refuge from cardiac
      impairment even if venous blood was fully oxygenated. By contrast, maximum
      adrenergic stimulation (500 nmol l(-1) adrenaline), fully protected maximum
      cardiac performance under hyperkalemic and acidotic conditions over a wide range
      of oxygen availability, from normoxia to 2.0 kPa, a venous oxygen tension close
      to routine values in vivo. Extending the level of hypoxia to 1.3 kPa resulted in
      a 43.6+/-2.8% decrease in maximum cardiac output, with hearts failing when tested
      at 1.0 kPa. Our results suggest that adrenergic stimulation of the trout heart is
      critical in maintaining maximum performance during prolonged swimming tests, and
      probably during all forms of exhaustive activity and recovery, when venous blood
      is hyperkalemic, acidotic and hypoxic.

PMID- 16788029
TI  - Mitochondrial mechanisms of cold adaptation in cod (Gadus morhua L.) populations
      from different climatic zones.
AB  - Adjustments in mitochondrial properties and capacities are crucial in
      acclimatization to seasonal cold as well as in evolutionary cold adaptation of
      marine ectotherms. To examine whether gene expression mechanisms contribute to
      different settings of aerobic capacities in populations of cod (Gadus morhua)
      along a latitudinal cline, maximum activities of key enzymes of mitochondrial
      metabolism and their respective mRNA levels were compared in white muscle and
      liver of cold (4 degrees C) and warm (10 degrees C) acclimated individuals from
      cod populations of the North Sea and the Barents Sea, respectively. In white
      muscle, cold acclimation caused a parallel increase in citrate synthase (CS) and
      in cytochrome c oxidase (COX) activities, but with a much larger effect in the
      cold eurythermal Arctic population. In liver, cold acclimation was accompanied by
      increments in CS activities, but differences between populations were minor.
      Overall COX activities in liver were not affected by cold acclimation, but were
      higher in the cold adapted population. In both populations increments in muscle
      CS capacities were tightly correlated with elevated mRNA levels, suggesting
      transcriptional control of citrate synthase levels in muscle. In liver, CS mRNA
      levels differed between populations but were not affected by cold acclimation, so
      that post-transcriptional control may contribute to elevated functional levels in
      this tissue. Mitochondrial-encoded COX2 mRNA levels were not limiting for
      functional activities in both tissues, in favour of post-transcriptional control
      or limitations by other transcripts of the COX complex. Altogether, the
      differentiation in gene expression between both populations was more strongly
      expressed at 4 degrees C. The comparison of functional levels and transcript
      levels may reflect genetic differentiation at functional sites, in line with
      genetic differences between the two populations previously established by non
      coding genetic markers.

PMID- 16788030
TI  - The effects of endogenous and exogenous nitric oxide on gut motility in zebrafish
      Danio rerio embryos and larvae.
AB  - Using motion analysis, the ontogeny of the nitrergic control system in the gut
      was studied in vivo in zebrafish Danio rerio embryos and larvae. For the first
      time we show the presence of a nitrergic tonus, modulating both anterograde and
      retrograde contraction waves in the intestine of developing zebrafish. At 4
      d.p.f. (days post fertilisation), the nitric oxide synthase (NOS) inhibitor L
      NAME (three boluses of 50-100 nl, 10(-3) mol l(-1)) increased the anterograde
      contraction wave frequency by 0.50+/-0.10 cycles min(-1). Subsequent application
      of the NO donor sodium nitroprusside (SNP; three boluses of 50-100 nl, 10(-4) mol
      l(-1)) reduced the frequency of propagating anterograde waves (-0.71+/-0.20
      cycles min(-1)). This coincided with the first appearance of an excitatory
      cholinergic tonus, observed in an earlier study. One day later, at 5 d.p.f., in
      addition to the effect on anterograde contraction waves, application of L-NAME
      increased (0.39+/-0.15 cycles min(-1)) and following SNP application reduced (
      1.61+/-0.36 cycles min(-1)) the retrograde contraction wave frequency. In
      contrast, at 3 d.p.f., when no spontaneous motility is observed, application of L
      NAME did not induce contraction waves in either part of the gut, indicating the
      lack of a functional inhibitory tonus at this early stage. Gut neurons expressing
      NOS-like immunoreactivity were present in the distal and middle intestine as
      early as 2 d.p.f., and at 1 day later in the proximal intestine. In conclusion,
      the present study suggests that a nitrergic inhibitory tonus develops shortly
      before or at the time for onset of exogenous feeding.

PMID- 16788031
TI  - The relationship between body size and evoked potentials from the statocysts of
      the prawn Palaemon serratus.
AB  - The organisation of the statocyst hair cells and auditory evoked potentials
      (AEPs) generated by the afferents in three body size classes of prawn (Palaemon
      serratus) have been studied using a combination of anatomical, electron
      microscopic and electrophysiological approaches. The statistical examination of
      the relationship between the sensory setae and body size showed an increase in
      both the length and number of statocyst hair cells as the animal grows. In view
      of this finding, the response of the statocyst organ to a 500 Hz tone burst was
      recorded from four specimens from each size class using two subcutaneous
      electrodes, positioned in the carapace close to the supraoesophageal ganglion and
      statocyst. Neither body size nor the number of afferents in the statocyst has any
      significant impact on the amplitude of AEPs in response to the 500 Hz tone burst.
      The findings of this study show that P. serratus is capable of hearing a 500 Hz
      tone regardless of body size, a finding that is of ecological importance when
      considering the effect of anthropogenic sound on crustaceans.

PMID- 16788032
TI  - Water vapour absorption in the penicillate millipede Polyxenus lagurus
      (Diplopoda: Penicillata: Polyxenida): microcalorimetric analysis of uptake
      kinetics.
AB  - The aberrant millipedes of the order Polyxenida are minute animals that inhabit
      xeric microclimates of bark and rock faces. The lichens and algae that provide
      their main food substrates tolerate extensive dehydration, effectively
      eliminating a liquid water source during periods of drought. In this study, we
      used microcalorimetry to test whether Polyxenus lagurus (L.) exploits active
      water vapour absorption (WVA) for water replenishment. Individual animals were
      pre-desiccated to 10-20% mass-loss and heat fluxes then monitored using a TAM
      2277 microcalorimeter. The calorimetric cell was exposed to an air stream
      increasing progressively in humidity from 84% to 96%. WVA was distinguishable as
      large exothermic fluxes seen in > or = 86% RH. Owing to very small and opposing
      heat fluxes from metabolism and passive water loss, the measured flux provided a
      good measure of water uptake. WVA showed an uptake threshold of 85% RH and linear
      sorption kinetics until >94% RH, when uptake became asymptotic. Uptake was rapid,
      and would allow recovery from 20% dehydration (by mass) in little over 5 h. The
      uptake flux scales proportional, variant mass (0.61), suggesting an area-limited
      mechanism. Polyxenus possesses a cryptonephric system, analogous to that of
      tenebrionid beetle larvae. Measurements of water absorption and desorption from
      faecal pellets voided in different humidities gave an estimated rectal humidity
      of 85.5%. The close congruence between this value and the WVA threshold provides
      evidence for a cryptonephric uptake mechanism derived independently from that of
      tenebrionids. Polyxenus represents the first documented example of WVA in the
      myriapod classes.

PMID- 16788034
TI  - Green land and blue sea: a coloured landscape in the orientation of the
      sandhopper Talitrus saltator (Montagu) (Amphipoda, Talitridae).
AB  - The use of the landscape in the zonal recovery of Talitrus saltator (Montagu) was
      demonstrated in the past using natural and artificial landscapes. Here we
      evaluate the importance of colour in the landscape orientation of sandhoppers.
      Adult individuals of T. saltator were released in a Plexiglas bowl under the sun,
      with a view of an artificial landscape: a black cardboard strip or a pair of
      differently coloured filters, each occupying 180 degrees of the horizon. Our
      results not only confirm the influence of the black and white artificial
      landscape-based compass cue on the zonal orientation of T. saltator, but also
      show that vision of a blue and green artificial landscape affects the direction
      of orientation; in fact, the orientation agreed with the directional indication
      of the landscape even when it contrasted with the sun compass indication. The
      same result was obtained with a blue-grey and green-grey landscape, but not with
      pairs of grey filters. Therefore, in the sandhoppers' visual world, a coloured
      landscape that matches the prevalent natural field colours greatly contributes to
      their directional choice.

PMID- 16788033
TI  - Metabolic organization of freshwater, euryhaline, and marine elasmobranchs:
      implications for the evolution of energy metabolism in sharks and rays.
AB  - To test the hypothesis that the preference for ketone bodies rather than lipids
      as oxidative fuel in elasmobranchs evolved in response to the appearance of urea
      based osmoregulation, we measured total non-esterified fatty acids (NEFA) in
      plasma as well as maximal activities of enzymes of intermediary metabolism in
      tissues from marine and freshwater elasmobranchs, including: the river stingray
      Potamotrygon motoro (<1 mmol l(-1) plasma urea); the marine stingray Taeniura
      lymma, and the marine shark Chiloscyllium punctatum (>300 mmol l(-1) plasma
      urea); and the euryhaline freshwater stingray Himantura signifer, which possesses
      intermediate levels of urea. H. signifer also were acclimated to half-strength
      seawater (15 per thousand) for 2 weeks to ascertain the metabolic effects of the
      higher urea level that results from salinity acclimation. Our results do not
      support the urea hypothesis. Enzyme activities and plasma NEFA in salinity
      challenged H. signifer were largely unchanged from the freshwater controls, and
      the freshwater elasmobranchs did not show an enhanced capacity for extrahepatic
      lipid oxidation relative to the marine species. Importantly, and contrary to
      previous studies, extrahepatic lipid oxidation does occur in elasmobranchs, based
      on high carnitine palmitoyl transferase (CPT) activities in kidney and rectal
      gland. Heart CPT in the stingrays was detectable but low, indicating some
      capacity for lipid oxidation. CPT was undetectable in red muscle, and almost
      undetectable in heart, from C. punctatum as well as in white muscle from T.
      lymma. We propose a revised model of tissue-specific lipid oxidation in
      elasmobranchs, with high levels in liver, kidney and rectal gland, low or
      undetectable levels in heart, and none in red or white muscle. Plasma NEFA levels
      were low in all species, as previously noted in elasmobranchs. D-beta
      hydroxybutyrate dehydrogenase (d-beta-HBDH) was high in most tissues confirming
      the importance of ketone bodies in elasmobranchs. However, very low d-beta-HBDH
      in kidney from T. lymma indicates that interspecific variability in ketone body
      utilization occurs. A negative relationship was observed across species between
      liver glutamate dehydrogenase activity and tissue or plasma urea levels,
      suggesting that glutamate is preferentially deaminated in freshwater
      elasmobranchs because it does not need to be shunted to urea production as in
      marine elasmobranchs.

PMID- 16788035
TI  - The origin of mean arterial and jugular venous blood pressures in giraffes.
AB  - Using a mechanical model of the giraffe neck and head circulation consisting of a
      rigid, ascending, 'carotid' limb, a 'cranial' circulation that could be rigid or
      collapsible, and a descending, 'jugular' limb that also could be rigid or
      collapsible, we have analyzed the origin of the high arterial and venous
      pressures in giraffe, and whether blood flow is assisted by a siphon. When the
      tubes were rigid and the 'jugular' limb exit was lower than the 'carotid' limb
      entrance a siphon operated, 'carotid' hydrostatic pressures became more negative,
      and flow was 3.3 l min(-1) but ceased when the 'cranial' and 'jugular' limbs were
      collapsible or when the 'jugular' limb was opened to the atmosphere. Pumping
      water through the model produced positive pressures in the 'carotid' limb similar
      to those found in giraffe. Applying an external 'tissue' pressure to the
      'jugular' tube during pump flow produced the typical pressures found in the
      jugular vein in giraffe. Constriction of the lowest, 'jugular cuff', portion of
      the 'jugular' limb showed that the cuff may augment the orthostatic reflex during
      head raising. Except when all tubes were rigid, pressures were unaffected by a
      siphon. We conclude that mean arterial blood pressure in giraffes is a
      consequence of the hydrostatic pressure generated by the column of blood in the
      neck, that tissue pressure around the collapsible jugular vein produces the known
      jugular pressures, and that a siphon does not assist flow through the cranial
      circulation.

PMID- 16788036
TI  - Pharmacological characterization of the ergot alkaloid receptor in the salivary
      gland of the ixodid tick Amblyomma hebraeum.
AB  - Female ticks of the family Ixodidae osmoregulate by secreting the excess fluid of
      the blood meal back into the host's circulation via the salivary glands. At least
      three receptors control salivary fluid secretion in the tick Amblyomma hebraeum:
      (1) dopamine (DA) stimulates fluid secretion via a DA receptor, (2) ergot
      alkaloids (ErAs) stimulate fluid secretion via an ErA-sensitive receptor (the
      natural ligand of which has not been identified), and (3) a GABA receptor
      potentiates the action of DA and ErAs. Here we present some pharmacological
      properties of the ErA-sensitive receptor. Of the 11 ErAs we tested, (i) four were
      complete agonists (approximate concentration eliciting 50% maximum response is
      given in parentheses): dihydroergotamine (0.02 micromol l(-1)), ergonovine (ErN;
      0.06 micromol l(-1)), methylergonovine (0.1 micromol l(-1)) and alpha
      ergocriptine (0.9 micromol l(-1)); (ii) three were ;incomplete agonists'
      (approximate concentration eliciting 20% maximum response is given in
      parentheses): ergocorninine (3.5 micromol l(-1)), ergocristinine (7.5 micromol l(
      1)) and ergocristine (10 micromol l(-1)); (C) three were partial agonists
      (approximate concentration eliciting the respective maximum response in
      parentheses): ergocornine (50% maximum by 1 micromol l(-1)), methysergide (28%
      maximum by 10 micromol l(-1)) and bromocriptine (22% maximum by 10 micromol l(
      1)); and (D) one had no activity up to 1 mmol l(-1): ergothioneine. Bromocriptine
      and methysergide did not antagonize the action of DA, but were effective
      competitive antagonists of ErN, with K(i)s of approximately 0.3 micromol l(-1)
      and 11 micromol l(-1), respectively. Ergothioneine was not an antagonist at
      either the DA- or ErA-sensitive receptor. The putative protein kinase C
      activators, 1-oleoyl-2-acetyl-sn-glycerol (OAG) and 1,2-dioctanoyl-sn-glycerol
      (DiC8), neither stimulated salivary fluid secretion nor potentiated the action of
      DA or ErN. The putative protein kinase C inhibitors, bisindolymaleimide (BIM) and
      calphostin C did not inhibit the action of DA or ErN, although low concentrations
      of calphostin C (10 nmol l(-1)) appeared to potentiate the action of DA but not
      ErN. The ion transport inhibitors, furosemide and amiloride (both up to 1 mmol l(
      1)), had no significant effect on DA-stimulated or ErN-stimulated fluid
      secretion.

PMID- 16788037
TI  - Storage and recovery of elastic potential energy powers ballistic prey capture in
      toads.
AB  - Ballistic tongue projection in toads is a remarkably fast and powerful movement.
      The goals of this study were to: (1) quantify in vivo power output and activity
      of the depressor mandibulae muscles that are responsible for ballistic mouth
      opening, which powers tongue projection; (2) quantify the elastic properties of
      the depressor mandibulae muscles and their series connective tissues using in
      situ muscle stimulation and force-lever studies; and (3) develop and test an
      elastic recoil model, based on the observed elastic properties of the depressor
      mandibulae muscles and series connective tissues, that accounts for displacement,
      velocity, acceleration and power output during ballistic mouth opening in toads.
      The results demonstrate that the depressor mandibulae muscles of toads are active
      for up to 250 ms prior to mouth opening. During this time, strains of up to 21.4%
      muscle resting length (ML) develop in the muscles and series connective tissues.
      At maximum isometric force, series connective tissues develop strains up to 14%
      ML, and the muscle itself develops strains up to 17.5% ML. When the mouth opens
      rapidly, the peak instantaneous power output of the depressor mandibulae muscles
      and series connective tissues can reach 9600 W kg(-1). The results suggest that:
      (1) elastic recoil of muscle itself can contribute significantly to the power of
      ballistic movements; (2) strain in series elastic elements of the depressor
      mandibulae muscle is too large to be borne entirely by the cross bridges and the
      actin-myosin filament lattice; and (3) central nervous control of ballistic
      tongue projection in toads likely requires the specification of relatively few
      parameters.

PMID- 16788038
TI  - Following the heart: temperature and salinity effects on heart rate in native and
      invasive species of blue mussels (genus Mytilus).
AB  - The three species of blue mussels, Mytilus trossulus Gould 1850, M. edulis
      Linnaeus 1758 and M. galloprovincialis Lamarck 1819, have distinct global
      distribution patterns that are hypothesized to reflect differences in their
      tolerances of temperature and salinity. We examined effects on heart rate (beats
      min(-1)) of acute exposure and acclimation to different combinations of
      temperature and salinity to test this hypothesis and, in the context of the
      invasive success of M. galloprovincialis, to gain insights into the factors that
      may explain the replacement of the temperate Pacific native, M. trossulus, by
      this Mediterranean Sea invader along much of the California coast. Heart rate of
      M. trossulus was significantly higher than that of M. galloprovincialis,
      consistent with evolutionary adaptation to a lower habitat temperature
      (temperature compensation) in the former species. Heart rates of M. trossulus/M.
      galloprovincialis hybrids were intermediate between those of the parental
      species. Following acclimation to 14 degrees C and 21 degrees C, heart rates of
      all species exhibited partial compensation to temperature. Heart rate increased
      with rising temperature until a high temperature was reached at which point
      activity fell sharply, the high critical temperature (H(crit)). H(crit) increased
      with increasing acclimation temperature and differed among species in a pattern
      that reflected their probable evolutionary adaptation temperatures: M.
      galloprovincialis is more heat tolerant than the other two congeners. Ability to
      sustain heart function in the cold also reflected evolutionary history: M.
      trossulus is more cold tolerant than M. galloprovincialis. Heart rates for all
      three congeners decreased gradually in response to acute reductions in salinity
      until a low salinity (S(crit)) was reached at which heart rate dropped
      precipitously. S(crit) decreased with decreasing salinity of acclimation and was
      generally lowest for M. galloprovincialis. Mortality during acclimation under
      common garden conditions was greatest in M. trossulus and was highest at high
      acclimation temperatures and salinities. These intrinsic differences in basal
      heart rate, thermal and salinity responses, acclimatory capacity, and
      survivorship are discussed in the contexts of the species' biogeographic
      patterning and, for the invasive species M. galloprovincialis, the potential for
      further range expansion along the Pacific coast of North America.

PMID- 16788039
TI  - 2-Hydroxyestradiol-17beta-induced oocyte maturation: involvement of cAMP-protein
      kinase A and okadaic acid-sensitive protein phosphatases, and their interplay in
      oocyte maturation in the catfish Heteropneustes fossilis.
AB  - In Heteropneustes fossilis, in vitro incubation of postvitellogenic follicles
      with 2-hydroxyestradiol-17beta (2-OHE2, 5 micromol l(-1)) decreased significantly
      the total cAMP level, concomitant with germinal vesicle breakdown (GVBD). The
      incubation of the follicles with cAMP or cAMP-elevating drugs [phosphodiesterase
      (PDE) inhibitors], such as IBMX (3-isobutyl-1-methyl-xanthine), theophylline and
      caffeine, inhibited the 2-OHE2-induced GVBD in a concentration-dependent manner.
      The magnitude of the response varied: both cAMP and IBMX were effective at all
      concentrations (0.1-2.0 mmol l(-1)), followed by theophylline (0.5-2.0 mmol l(
      1)) and caffeine (1-2.0 mmol l(-1)). The protein kinase A (PKA) inhibitor H89
      stimulated oocyte maturation in a concentration-dependent manner. However, when
      co-incubated with 2-OHE2 for 24 h it produced a biphasic effect: low
      concentrations (0.1 and 1.0 micromol l(-1)) did not alter the 2-OHE2-induced
      GVBD, but high concentrations (5 and 10 micromol l(-1)) inhibited it. The
      incubation of the follicles with H89 lowered the inhibitory effect of IBMX on the
      2-OHE2-induced GVBD. The incubation of the follicles with okadaic acid (OA), a
      protein phosphatase 1 and 2A inhibitor did not affect GVBD but when co-incubated
      with 2-OHE2, it enhanced the GVBD response. OA reversed the inhibitory effect of
      IBMX. The results suggest that OA may overcome the inhibition of 2-OHE2-induced
      GVBD by IBMX at a step distal to the cAMP-PKA pathway.

PMID- 16788040
TI  - The effect of myoglobin concentration on aerobic dive limit in a Weddell seal.
AB  - One physiological adaptation for prolonged dive duration in marine mammals is an
      elevated myoglobin (Mb) concentration in skeletal muscle. To determine the
      influence of Mb concentration on the aerobic dive limit (ADL), we modified a
      previously published model that simulated aerobic dives in a Weddell seal
      (Leptonychotes weddellii) and ran it for four Mb concentrations: 5, 27, 54 and
      108 g Mb kg(-1) muscle representing 7%, 50%, 100% and 200%, respectively, of the
      normal Mb concentration in Weddell seal skeletal muscle. The model was run at
      increasing levels of muscular exertion and under postabsorptive and postprandial
      conditions to determine their effect on ADL. For each set of conditions, the
      model was also run at different levels of cardiac output (i.e. the dive response
      was varied) to determine the level of convective oxygen transport that optimized
      the ADL. In a postabsorptive state at a routine level of muscular exertion for a
      diving Weddell seal, a decrease in Mb concentration to 7% of normal caused a 39%
      decrease in the ADL (18 min to 11 min), while doubling the Mb concentration
      increased the ADL by 30% (18 min to 24 min). Under postprandial conditions at a
      routine level of muscular exertion, doubling the Mb concentration did not
      increase the ADL (12 min). The convective oxygen transport needed to meet the
      metabolic demands (Heat Increment of Feeding, HIF) of the splanchnic organs
      during digestion and assimilation required a cardiac output that was not optimal
      for the efficient use of muscle oxygen stores. This resulted in an over perfusion
      of the muscles and incomplete use of myoglobin-bound oxygen. As a result, the
      postprandial ADL was limited by the amount of oxygen stored in the blood, and
      increasing the Mb concentration had no effect on the ADL. We hypothesize that
      myoglobin concentration is optimized for the type and duration of dives routinely
      made by Weddell seals, and that a further increase may not increase the ADL for
      most free-ranging dives.

PMID- 16788042
TI  - Functional evidence for the presence of a carbonic anhydrase repressor in the
      eyestalk of the euryhaline green crab Carcinus maenas.
AB  - Carbonic anhydrase (CA) activity and relative expression of CA mRNA were measured
      in the gills of the euryhaline green crab Carcinus maenas in response to eyestalk
      ablation (ESA), injection of eyestalk extract and exposure to low salinity. For
      crabs acclimated to 32 p.p.t. salinity, ESA alone resulted in an increase in both
      CA activity and relative mRNA expression in the posterior, ion-transporting
      gills, but not in the anterior, respiratory gills. The ESA-stimulated increase in
      CA activity was abolished by injections of extracts of eyestalks taken from crabs
      acclimated to 32 p.p.t. salinity. Transfer of intact crabs from 32 to 10 p.p.t.
      salinity for 7 days resulted in an eightfold increase in CA activity and a
      sixfold increase in mRNA expression in posterior gills. ESA potentiated the
      normal low salinity-mediated CA induction by 23%. Daily injections of eyestalk
      extract reduced low salinity-stimulated CA induction by nearly 50% in intact
      crabs and by almost 75% in eyestalk ablated crabs. A 4-day transfer to 10 p.p.t.
      salinity also caused significant increases in both CA activity and mRNA
      expression in posterior gills, and ESA resulted in a 32% increase in the normal
      degree of CA induction. Daily injections of eyestalk extracts reduced CA
      induction in a dose-dependent manner over the 4-day time course. When CA
      induction was reduced by 66%, hemolymph osmotic regulation was also disrupted.
      These results are functional evidence for the presence of a CA repressor in the
      major endocrine complex of the crab, the eyestalk. This compound appears to
      function in keeping CA expression at low, baseline levels in crabs at high
      salinity. Exposure to low salinity removes the effects of the putative repressor,
      allowing CA expression, and thus CA activity, to increase.

PMID- 16788041
TI  - Effect of pH on trout blood vessels and gill vascular resistance.
AB  - pH is recognized as a modulator of vascular smooth muscle (VSM) tone in mammalian
      vessels, but little is known about its effects on fish VSM. We investigated the
      effects of extracellular and intracellular pH (pH(o) and pH(i), respectively) on
      isolated vessels from steelhead and rainbow trout (Oncorhynchus mykiss, Skamania
      and Kamloops strains, respectively) and of pH(o) on perfused gills from rainbow
      trout. In otherwise unstimulated (resting) efferent branchial (EBA) and coeliaco
      mesenteric arteries (CMA), anterior cardinal veins (ACV) and perfused gills,
      increasing pH(o) from 6.8 to 8.8-9.0 produced a dose-dependent contraction or
      increase in gill resistance (R(GILL)) with an estimated half-maximal response of
      8.0-8.2. pH(o) interactions with other contractile stimuli were agonist specific;
      more force was developed at low pH(o) in ligand-mediated (arginine vasotocin)
      contractions, whereas depolarization-mediated (40-80 mmol l(-1) KCl) contractions
      were greatest at high pH(o). Increasing pH(i) by application of 40 mmol l(-1)
      NH4Cl produced sustained contraction in afferent branchial arteries (ABA)
      suggesting that these vessels could not readily restore pH(i). NH(4)Cl
      application only transiently contracted EBA and CMA in Hepes buffer, whereas it
      produced a slight, but prolonged, relaxation of EBA and CMA in Cortland buffer.
      The buffer effect was due to the presence of Hepes and in this environment EBA
      and CMA appeared to readily restore pH(i). Increasing pH(i) in KCl-contracted EBA
      in Hepes produced an additional contraction, whereas ligand-contracted
      (thromboxane A2 analog, U-46619) EBA relaxed. Reducing pH(i) (NH(4)Cl washout)
      transiently contracted resting EBA and CMA in both Hepes and Cortland buffer.
      NH4Cl washout produced an additional, transient contraction of both KCl- and U
      46619-contracted EBA in Hepes. EBA contractions produced by increased pH(i)
      depend primarily on intracellular Ca2+, whereas both intracellular and
      extracellular Ca2+ contributed to the response to decreased pH(i). Three cycles
      of perfusate acidification (pH(o) 7.8 to 6.2 and back to 7.8) reproducibly
      halved, then restored R(GILL) with no adverse effects, indicating that this was
      not a pathophysiological response. These studies show that the general effects of
      pH on VSM are phylogenetically conserved from fish to mammals but even within a
      species there are vessel-specific differences. Furthermore, as fish are exposed
      to substantial fluctuations in environmental (and therefore plasma) pH, the
      obligatory response of fish VSM to these changes may have substantial impact on
      cardiovascular homeostasis.

PMID- 16788043
TI  - Overview: membrane traffic in multicellular systems: more than just a
      housekeeper.
AB  - Membrane traffic is a fundamental cellular function by which molecules are
      transported between organelles in the post-Golgi network. Accumulating evidence
      supports the notion that membrane traffic is not only indispensable for normal
      cellular function and maintenance of cellular viability by playing housekeeping
      roles, but also critical for various functions characteristic of multicellular
      organisms. This Minireview series will focus on the latter aspects of membrane
      traffic. The topics discussed are: the pathophysiological impact of clathrin
      associated adaptor protein (AP) complexes, the significance of membrane traffic
      in Alzheimer's disease, regulated exocytosis of insulin, secretory lysosomes in
      immune response, exosomes in physiology and pathology, viral and mammalian
      ubiquitin ligases modulating immune response, membrane traffic of bacterial
      toxins, and containment of bacterial infection by autophagy.

PMID- 16788044
TI  - Physiological roles of clathrin adaptor AP complexes: lessons from mutant
      animals.
AB  - Clathrin-associated adaptor protein (AP) complexes play a key role in the
      transport of proteins, by regulating the formation of transport vesicles as well
      as cargo selection, between organelles of the post-Golgi network, namely, the
      trans-Golgi network (TGN), endosomes, lysosomes and the plasma membrane. Evidence
      has been accumulating for the physiological importance of AP complexes.
      Deficiency in AP-1A or AP-2 results in embryonic lethality in mice, indicating
      that these AP complexes are essential for normal development of embryos in
      mammals. In contrast, mutations in the genes encoding subunits of AP-3A cause an
      autosomal recessive disorder, Hermansky-Pudlak syndrome in human and its disease
      models in mice. Knockout mice for the neuron-specific AP-3B suffer from epileptic
      seizure. Further studies on the physiological and pathological aspects of AP
      complexes will not only be beneficial for better understanding of developmental
      biology and medical sciences, but also deepen our insight into the molecular
      mechanisms of vesicular traffic.

PMID- 16788045
TI  - Trafficking of Alzheimer's disease-related membrane proteins and its
      participation in disease pathogenesis.
AB  - Alzheimer's disease (AD) is a common neurodegenerative disorder that causes
      senile dementia. The pathological characteristics are the appearance of
      neurofibrillary tangles comprising abnormally phosphorylated tau and senile
      plaques composed of amyloid beta-protein depositions. Amyloid beta-protein
      precursor (APP) and presenilin (PS) are known to be causative genes of familial
      AD. Recent analyses have documented that APP functions in the axonal transport of
      vesicles and PS regulates intracellular protein trafficking. Dystrophic neurites,
      in which APP and Alcadein accumulate in swollen axons, are also observed in AD
      brain. These pathological characteristics and the features of AD-related proteins
      suggest that AD is a disease of the vesicular transport system. Here we review
      recent progress of research on AD pathogenesis from the viewpoint of membrane
      trafficking.

PMID- 16788047
TI  - Identification and reverse genetic analysis of mitochondrial processing peptidase
      and the core protein of the cytochrome bc1 complex of Caenorhabditis elegans, a
      model parasitic nematode.
AB  - Mitochondria could be a good target for anti-parasitic drugs. The alpha and beta
      subunits of mitochondrial processing peptidase (MPP) and the core subunits of the
      cytochrome bc1 complex, UCR-1 and UCR-2, are homologous to one another and are
      important for mitochondrial functions. However, our knowledge of these proteins
      in nematodes is very limited. Caenorhabditis elegans, a free-living nematode, has
      six genes coding for proteins homologous to these subunits. On primary structure
      comparison, and immunochemical and enzymological analyses, the gene products were
      assigned as follows: Y71G12B.24, alpha-MPP; ZC410.2, beta-MPP; F56D2.1, UCR-1;
      VW06B3R.1, T10B10.2; and T24C4.1, UCR-2. The primary structures of beta-MPP and
      UCR-1 from Brugia malayi, a parasitic nematode causing human filariasis, were
      deduced from their cDNA structures. Phylogenetic analysis showed that the UCR-1s
      from both C. elegans and B. malayi were less related to mammalian UCR-1s than to
      MPPs from various organisms. MPP and the bc1 complex are essential for the life
      cycle of C. elegans, because their reverse genetic inhibition is lethal. This
      suggests the possibility that these proteins are also essential for the viability
      of B. malayi and other parasitic nematodes, and are potential targets for anti
      parasitic agents.

PMID- 16788046
TI  - The hemocyanin of the shamefaced crab Calappa granulata: structural-functional
      characterization.
AB  - Arthropod hemocyanins (Hcs) transport and store oxygen and are composed of six
      subunits, or multiples thereof depending on the species. Calappa granulata Hc is
      found as a mixture of dodecamers (95%) and hexamers (5%). Removal of calcium ions
      and alkaline pH induce an incomplete partially reversible dissociation of
      dodecameric Hc. Two-dimensional electrophoretic pattern of dissociated Hc
      indicated a large heterogeneity in Hc subunit: most differences are likely to be
      explained by post-translational modifications. Dodecameric Hc showed a large Bohr
      effect (Deltalog P50/DeltapH = -0.95) and a normal cooperativity (h50 values =
      2.7 +/- 0.2) in the presence of 10 mM CaCl2. The hexameric molecule displayed
      lower Bohr effect and cooperativity than the dodecamer. Lactate effect on the
      oxygen affinity (Deltalog P50 = 0.55) and the increase of lactate concentrations
      in animals kept in emersion were related to the increased oxygen requirements
      that occur during hypoxia in vivo. Calcium affects oxygen affinity only at high
      concentrations: this Hc appeared to lack the calcium high-affinity binding sites
      found in other species. The effect of temperature on both oxygen affinity and
      cooperativity was measured in the absence and presence of 10 mM lactate, allowing
      calculation of the exothermic contribution of lactate binding (DeltaH = -25 kJ
      mol(-1)).

PMID- 16788048
TI  - Superoxide production in human neutrophils is enhanced by treatment with
      transmembrane peptides derived from human formyl peptide receptor.
AB  - Formyl peptide receptor (FPR) mediates a number of important host defense
      functions. Although studies have been performed on the ligand binding site of
      FPR, FPR dynamic behavior such as receptor dimerization on the cell surface
      remains unknown. Recently, peptides derived from the transmembrane (TM) domains
      of GPCRs were shown to disrupt dimer formation by receptors and to result in
      specific regulation of receptor function. To reveal the function of FPR TM
      domains, hFPRTM peptides derived from FPR were synthesized, and their biological
      activities were evaluated with human neutrophils. Synthetic peptides did not
      exhibit agonistic or antagonistic activity toward superoxide anion production.
      However, Neutrophils treated with hFPRTM4 produced 4-fold superoxide anion
      compared with untreated cells when stimulated with FPR agonist fMLP. Short
      peptide fragments derived from the fourth TM region of FPR did not enhance
      superoxide anion production, which suggests that hFPRTM4 did not behave as a
      ligand. CD and fluorescence spectra suggested that hFPRTM peptides were inserted
      into the membrane. The addition of hFPRTM4 increased the intracellular calcium
      concentration, which meant the peptide activated some membrane protein on the
      cell surface. The present study suggests that the fourth TM domain of FPR has a
      function related to a priming effect.

PMID- 16788049
TI  - Aggregation of partially unfolded Myosin subfragment-1 into spherical oligomers
      with amyloid-like dye-binding properties.
AB  - Proteolytic myosin subfragment 1 (S1) is known to be partially unfolded in its 50
      kDa subdomain by mild heat treatment at 35 degrees C [Burke et al. (1987)
      Biochemistry 26, 1492-1496]. Here, we report that this partial unfolding is
      accompanied by aggregation of S1 protein. Characteristics of the aggregate thus
      formed were: (i) formation of transparent sediment under centrifugation at
      183,000 x g; (ii) amyloid-like, dye-binding properties such as Congo red-binding
      and Thioflavin T fluorescence enhancement; (iii) a uniformly sized spherical
      appearance in electron micrographs; and (iv) sensitivity to tryptic digestion.
      Gel filtration analysis of the aggregation process indicates that the spheroid
      was formed through an intermediate oligomeric stage. The aggregate inhibited
      spontaneous aggregation of an isolated 50 kDa fragment into a large amorphous
      mass. The remaining native regions in the partially unfolded S1 were probably
      responsible for this effect. These results show that, unlike the 50-kDa fragment,
      the partially unfolded S1 molecules do not form amorphous aggregates but assemble
      into spherical particles. The native regions in partially unfolded S1 may be a
      determinant of aggregate morphology.

PMID- 16788051
TI  - Comparison of the wild-type alpha-amylase and its variant enzymes in Bacillus
      amyloliquefaciens in activity and thermal stability, and insights into
      engineering the thermal stability of bacillus alpha-amylase.
AB  - The starch hydrolysis activity and thermal stability of Bacillus
      amyloliquefaciens alpha-amylase (wild-type enzyme or WT) and its variant enzymes,
      designated as M77, M111, and 21B, were compared. All have an optimal pH at around
      6, as well as almost the same reaction rates and Km and kcat values. The optimal
      temperature in the absence of Ca2+ ions is 60 degrees C for WT and M77 and 40
      degrees C for M111 and 21B. Those of M111 and 21B rose to 50-60 degrees C upon
      the addition of 5 mM CaCl2, while those of WT and M77 did not change. The
      dissociation constants Kd for Ca2+ to WT and M77 are much lower than those of
      M111 and 21B. Asp233 in WT is replaced by Asn in M111 and 21B, while it is
      retained in M77, suggesting that Asp233 is involved in the thermal stability of
      the enzyme through Ca2+ ion binding. These findings provide insight into
      engineering the thermal stability of B. amyloliquefaciens alpha-amylase, which
      would be useful for its applications in the baking industry and in glucose
      manufacturing.

PMID- 16788050
TI  - Comparison of starch hydrolysis activity and thermal stability of two Bacillus
      licheniformis alpha-amylases and insights into engineering alpha-amylase variants
      active under acidic conditions.
AB  - Bacillus licheniformis alpha-amylase (BLA) is widely used in various procedures
      of starch degradation in the food industry, and a BLA species with improved
      activity at higher temperature and under acidic conditions is desirable. Two BLA
      species, designated as PA and MA, have been isolated from the wild-type B.
      licheniformis strain and a mutant strain, respectively. In this study, their
      starch-hydrolysis activity and thermal stability were examined. MA showed higher
      activity than PA, especially at acidic pH (pH 5.0-5.5), and even after 1 h of
      treatment at 90 degrees C. MA was active in the range of pH 4.0-8.0, which is
      much wider than that (pH 4.5-7.5) of PA. It was shown that the proton
      dissociation constants on the acidic and alkaline sides (pKa1 and pKa2) were
      shifted to more acidic and basic values, respectively, by the mutation of PA to
      MA. The activation energy and thermodynamic parameters for their thermal
      inactivation indicate that MA is more thermally stable and catalytically active
      than PA, suggesting that MA could be useful for glucose-production process
      coupled with reactions catalyzed by beta-amylase.

PMID- 16788052
TI  - Engineering of the pH-dependence of thermolysin activity as examined by site
      directed mutagenesis of Asn112 located at the active site of thermolysin.
AB  - Asn112 is located at the active site of thermolysin, 5-8 A from the catalytic
      Zn2+ and catalytic residues Glu143 and His231. When Asn112 was replaced with Ala,
      Asp, Glu, Lys, His, and Arg by site-directed mutagenesis, the mutant enzymes
      N112D and N112E, in which Asn112 is replaced with Asp and Glu, respectively, were
      secreted as an active form into Escherichia coli culture medium, while the other
      four were not. In the hydrolysis of a neutral substrate N-[3-(2-furyl)acryloyl]
      Gly-L-Leu amide, the kcat/Km values of N112D and N112E exhibited bell-shaped pH
      dependence, as did the wild-type thermolysin (WT). The acidic pKa of N112D was
      5.7 +/- 0.1, higher by 0.4 +/- 0.2 units than that of WT, suggesting that the
      introduced negative charge suppressed the protonation of Glu143 or Zn2+-OH. In
      the hydrolysis of a negatively charged substrate, N-carbobenzoxy-l-Asp-l-Phe
      methyl ester (ZDFM), the pH-dependence of kcat/Km of the mutants decreased with
      increase in pH from 5.5 to 8.5, while that of WT was bell-shaped. This difference
      might be explained by the electrostatic repulsion between the introduced Asp/Glu
      and ZDFM, suggesting that introducing ionizing residues into the active site of
      thermolysin might be an effective means of modifying its pH-activity profile.

PMID- 16788053
TI  - Molten globule-like state of bovine carbonic anhydrase in the presence of
      acetonitrile.
AB  - We have evaluated the effects of acetonitrile on the structure and function of
      bovine carbonic anhydrase II. The potential structural and functional changes in
      carbonic anhydrase in the presence of different acetonitrile/buffer ratios (0%,
      17.5% and 47.5% v/v) were determined using a variety of methods. These included
      simple spectrophotometric methods to record enzyme velocity, fluorescence
      measurements and calculation of accessible surface area (ASA) to identify
      possible alterations in tertiary structure of the protein, CD measurements to
      search for secondary structure conversions, and thermal scanning to determine
      structural stability of the protein in different media. The Far-UV CD studies
      indicated that carbonic anhydrase, for the most part, retains its secondary
      structure in the presence of acetonitrile. Fluorescence measurements using iodide
      ion and ANS along with ASA calculations revealed that in the presence of
      acetonitrile some degree of conformational change occurs in the carbonic
      anhydrase structure. In addition to the hydrophobic pockets, two additional
      tryptophanyl residues become exposed to the solvent, thereby increasing the
      surface hydrophobicity of the protein. These alterations dramatically reduce the
      catalytic activity, thermal stability, and aggregation velocity of the enzyme.
      Thus, our results support a molten globule-like structure of carbonic anhydrase
      in the presence of acetonitrile.

PMID- 16788054
TI  - A retaining endo-beta-mannosidase from a dicot plant, cabbage.
AB  - An endo-beta-mannosidase [EC 3.2.1.152, glycoside hydrolase family 2], which
      hydrolyzes the Manbeta1-4GlcNAc linkage of N-glycans in an endo-manner, has been
      found in plant tissues [Ishimizu, T., Sasaki, A., Okutani, S., Maeda, M.,
      Yamagishi, M., and Hase, S. (2004) J. Biol. Chem. 279, 38555-38562]. So far, this
      glycosidase has been purified only from a monocot plant, a lily. Here, an endo
      beta-mannosidase was purified from a dicot plant, cabbage (Brassica oleracea),
      and characterized. The cabbage endo-beta-mannosidase consists of four
      polypeptides. These four polypeptides are encoded by a single gene, whose
      nucleotide sequence is homologous to those of the lily and Arabidopsis endo-beta
      mannosidase genes. 1H NMR analysis of the stereochemistry of the hydrolysis of
      pyridylaminated (PA) Manalpha1-6Manbeta1-4GlcNAcbeta1-4GlcNAc showed that the
      cabbage endo-beta-mannosidase is a retaining glycoside hydrolase, as are other
      glycoside hydrolase family 2 enzymes. The enzymatic characteristics, including
      substrate specificity, of the cabbage enzyme are very similar to those of the
      lily enzyme. These endo-beta-mannosidases specifically act on Man(n)Manalpha1
      6Manbeta1-4GlcNAcbeta1-4GlcNAc-PA (n = 0 to 2). These results suggest that the
      endo-beta-mannosidase is present in at least the angiosperms, and has common
      roles, such as the degradation of N-glycans.

PMID- 16788055
TI  - Deletion analysis of the subunit genes of V-type Na+-ATPase from Enterococcus
      hirae.
AB  - The V1Vo-ATPase from Enterococcus hirae catalyzes ATP hydrolysis coupled with
      sodium translocation. Mutants with deletions of each of 10 subunits (NtpA, B, C,
      D, E, F, G, H, I, and K) were constructed by insertion of a chloramphenicol
      acetyltransferase gene into the corresponding subunit gene in the genome.
      Measurements of cell growth rates, 22Na+ efflux activities, and ATP hydrolysis
      activities of the membranes of the deletion mutants indicated that V-ATPase
      requires nine of the subunits, the exception being the NtpH subunit. The results
      of Western blotting and V1-ATPase dissociation analysis suggested that the A, B,
      C, D, E, F, and G subunits constitute the V1 moiety, whereas the V0 moiety
      comprises the I and K subunits.

PMID- 16788056
TI  - Molecular cloning of a novel type of rat cytoplasmic 17beta-hydroxysteroid
      dehydrogenase distinct from the type 5 isozyme.
AB  - Rat liver contains two cytosolic enzymes (TBER1 and TBER2) that reduce 6-tert
      butyl-2,3-epoxy-5-cyclohexene-1,4-dione into its 4R- and 4S-hydroxy metabolites.
      In this study, we cloned the cDNA for TBER1 and examined endogenous substrates
      using the homogenous recombinant enzyme. The cDNA encoded a protein composed of
      323 amino acids belonging to the aldo-keto reductase family. The recombinant
      TBER1 efficiently oxidized 17beta-hydroxysteroids and xenobiotic alicyclic
      alcohols using NAD+ as the preferred coenzyme at pH 7.4, and showed low activity
      towards 20alpha- and 3alpha-hydroxysteroids, and 9-hydroxyprostaglandins. The
      enzyme was potently inhibited by diethylstilbestrol, hexestrol and zearalenone.
      The coenzyme specificity, broad substrate specificity and inhibitor sensitivity
      of the enzyme differed from those of rat NADPH-dependent 17beta-hydroxysteroid
      dehydrogenase type 5, which was cloned from the liver and characterized using the
      recombinant enzyme. The mRNA for TBER1 was highly expressed in rat liver,
      gastrointestinal tract and ovary, in contrast to specific expression of 17beta
      hydroxysteroid dehydrogenase type 5 mRNA in the liver and kidney. Thus, TBER1
      represents a novel type of 17beta-hydroxysteroid dehydrogenase with unique
      catalytic properties and tissue distribution. In addition, TBER2 was identified
      as 3alpha-hydroxysteroid dehydrogenase on chromatographic analysis of the enzyme
      activities in rat liver cytosol and characterization of the recombinant 3alpha
      hydroxysteroid dehydrogenase.

PMID- 16788057
TI  - Effects of high concentration of salts on the esterase activity and structure of
      a kiwifruit peptidase, actinidain.
AB  - Effects of salts on the activity and stability of actinidain were examined. With
      increasing salt concentration up to 0.5 M, the activity (kcat/Km) for N-alpha-Cbz
      L-lysine p-nitrophenyl ester decreased to 40% of that in the absence of salt. The
      inhibitor constant Ki of LiCl, NaCl, and KCl was 0.16-0.43 M. With 3 M KCl and
      NaCl, the specificity constant kcat/Km recovered to 110 and 75%, respectively. No
      re-activation was observed with LiCl. The inhibition and re-activation were
      dependent on the changes in both Km and kcat, whereas no CD change was observed.
      The tryptophan fluorescence of actinidain was not affected by 0-0.5 M salt, but a
      considerable decrease in its intensity was observed with increasing salt
      concentration from 0.5 to 3.0 M. These results suggest that the inhibition
      observed with the lower salt concentration (<0.5 M) is due to attenuation of the
      electrostatic interaction between the enzyme and substrate, and the higher
      concentration (0.5-3.0 M) induces structural change in the states of tryptophan
      residues, which is associated with the re-activation. Actinidain keeps
      considerably high activity and stability even in the presence of 3 M salts.

PMID- 16788058
TI  - Biosynthesis of archaeal membrane lipids: digeranylgeranylglycerophospholipid
      reductase of the thermoacidophilic archaeon Thermoplasma acidophilum.
AB  - The basic core structure of archaeal membrane lipids is 2,3-di-O-phytanyl-sn
      glyceryl phosphate (archaetidic acid), which is formed by the reduction of 2,3-di
      O-geranylgeranylglyceryl phosphate. The reductase activity for the key enzyme in
      membrane lipid biosynthesis, 2,3-digeranylgeranylglycerophospholipid reductase,
      was detected in a cell free extract of the thermoacidophilic archaeon
      Thermoplasma acidophilum. The reduction activity was found in the membrane
      fraction, and FAD and NADH were required for the activity. The reductase was
      purified from a cell free extract by ultracentrifugation and four chromatographic
      steps. The purified enzyme showed a single band at ca. 45 kDa on SDS-PAGE, and
      catalyzed the formation of archaetidic acid from 2,3-di-O-geranylgeranylglyceryl
      phosphate. Furthermore, the enzyme also catalyzed the reduction of 2,3-di-O
      geranylgeranylglyceryl phosphate analogues such as 2,3-di-O-phytyl-sn-glyceryl
      phosphate, 3-O-(2,3-di-O-phytyl-sn-glycero-phospho)-sn-glycerol and 2,3-di-O
      phytyl-sn-glycero-phosphoethanolamine. The N-terminal 20 amino acid sequence of
      the purified enzyme was determined and was found to be identical to the sequence
      encoded by the Ta0516m gene of the T. acidophilum genome. The present study
      clearly demonstrates that 2,3-digeranylgeranylglycerophospholipid reductase is a
      membrane associated protein and that the hydrogenation of each double bond of 2,3
      digeranylgeranylglycerophospholipids is catalyzed by a single enzyme.

PMID- 16788059
TI  - Proinsulin C-peptide stimulates a PKC/IkappaB/NF-kappaB signaling pathway to
      activate COX-2 gene transcription in Swiss 3T3 fibroblasts.
AB  - Proinsulin C-peptide causes multiple molecular and physiological effects, and
      improves renal and neuronal dysfunction in patients with diabetes. However,
      whether C-peptide controls the inhibitor kappaB (IkappaB)/NF-kappaB-dependent
      transcription of genes, including inflammatory genes is unknown. Here we showed
      that 1 nM C-peptide increased the expression of cyclooxygenase-2 (COX-2) mRNA and
      its protein in Swiss 3T3 fibroblasts. Consistently, C-peptide enhanced COX-2 gene
      promoter-activity, which was inhibited by GF109203X and Go6976, specific PKC
      inhibitors, and BAY11-7082, a specific nuclear factor-kappaB (NF-kappaB)
      inhibitor, accompanied by increased phosphorylation and degradation of IkappaB.
      These results suggest that C-peptide stimulates the transcription of inflammatory
      genes via activation of a PKC/IkappaB/NF-kappaB signaling pathway.

PMID- 16788060
TI  - Spontaneous neuronal activity distinguishes human dorsal and ventral attention
      systems.
AB  - On the basis of task-related imaging studies in normal human subjects, it has
      been suggested that two attention systems exist in the human brain: a bilateral
      dorsal attention system involved in top-down orienting of attention and a right
      lateralized ventral attention system involved in reorienting attention in
      response to salient sensory stimuli. An important question is whether this
      functional organization emerges only in response to external attentional demands
      or is represented more fundamentally in the internal dynamics of brain activity.
      To address this question, we examine correlations in spontaneous fluctuations of
      the functional MRI blood oxygen level-dependent signal in the absence of task,
      stimuli, or explicit attentional demands. We identify a bilateral dorsal
      attention system and a right-lateralized ventral attention system solely on the
      basis of spontaneous activity. Further, we observe regions in the prefrontal
      cortex correlated with both systems, a potential mechanism for mediating the
      functional interaction between systems. These findings demonstrate that the
      neuroanatomical substrates of human attention persist in the absence of external
      events, reflected in the correlation structure of spontaneous activity.

PMID- 16788061
TI  - A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is
      induced by the Cry1Ab toxin of Bacillus thuringiensis.
AB  - Many pathogenic organisms and their toxins target host cell receptors, the
      consequence of which is altered signaling events that lead to aberrant activity
      or cell death. A significant body of literature describes various molecular and
      cellular aspects of toxins associated with bacterial invasion, colonization, and
      host cell disruption. However, there is little information on the molecular and
      cellular mechanisms associated with the insecticidal action of Bacillus
      thuringiensis (Bt) Cry toxins. Recently, we reported that the Cry1Ab toxin
      produced by Bt kills insect cells by activating a Mg(2+)-dependent cytotoxic
      event upon binding of the toxin to its receptor BT-R(1). Here we show that
      binding of Cry toxin to BT-R(1) provokes cell death by activating a previously
      undescribed signaling pathway involving stimulation of G protein (G(alphas)) and
      adenylyl cyclase, increased cAMP levels, and activation of protein kinase A.
      Induction of the adenylyl cyclase/protein kinase A pathway is manifested by
      sequential cytological changes that include membrane blebbing, appearance of
      ghost nuclei, cell swelling, and lysis. The discovery of a toxin-induced cell
      death pathway specifically linked to BT-R(1) in insect cells should provide
      insights into how insects evolve resistance to Bt and into the development of
      new, safer insecticides.

PMID- 16788062
TI  - Reversible lysine acetylation controls the activity of the mitochondrial enzyme
      acetyl-CoA synthetase 2.
AB  - We report that human acetyl-CoA synthetase 2 (AceCS2) is a mitochondrial matrix
      protein. AceCS2 is reversibly acetylated at Lys-642 in the active site of the
      enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates
      Lys-642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the
      acetyl-CoA synthetase activity of AceCS2. This report identifies the first
      acetylated substrate protein of SIRT3. Our findings show that a mammalian sirtuin
      directly controls the activity of a metabolic enzyme by means of reversible
      lysine acetylation. Because the activity of a bacterial ortholog of AceCS2,
      called ACS, is controlled via deacetylation by a bacterial sirtuin protein, our
      observation highlights the conservation of a metabolic regulatory pathway from
      bacteria to humans.

PMID- 16788063
TI  - Loss of Aif function causes cell death in the mouse embryo, but the temporal
      progression of patterning is normal.
AB  - Apoptosis-inducing factor (AIF) is an evolutionarily conserved, ubiquitously
      expressed flavoprotein with NADH oxidase activity that is normally confined to
      mitochondria. In mammalian cells, AIF is released from mitochondria in response
      to apoptotic stimuli and translocates to the nucleus where it is thought to bind
      DNA and contribute to chromatinolysis and cell death in a caspase-independent
      manner. Here we describe the consequences of inactivating Aif in the early mouse
      embryo. Unexpectedly, we found that both the apoptosis-dependent process of
      cavitation in embryoid bodies and apoptosis associated with embryonic neural tube
      closure occur in the absence of AIF, indicating that Aif function is not required
      for apoptotic cell death in early mouse embryos. By embryonic day 9 (E9), loss of
      Aif function causes abnormal cell death, presumably because of reduced
      mitochondrial respiratory chain complex I activity. Because of this cell death,
      Aif null embryos fail to increase significantly in size after E9. Remarkably,
      patterning processes continue on an essentially normal schedule, such that E10
      Aif null embryos with only approximately 1/10 the normal number of cells have the
      same somite number as their wild-type littermates. These observations show that
      pattern formation in the mouse can occur independent of embryo size and cell
      number.

PMID- 16788064
TI  - A Caenorhabditis elegans tissue model of radiation-induced reproductive cell
      death.
AB  - We have developed a tissue model of radiation-induced reproductive cell death in
      the nematode Caenorhabditis elegans. Reproductive cell death is the primary mode
      of death in tissue multipotential precursor cells, or "clonogens," the targets of
      cytotoxic therapy, whose elimination results in normal tissue damage as well as
      solid-tumor eradication. Through extensive morphologic and genetic analysis, we
      have confirmed that cell death in this model represents reproductive cell death
      in isolation from apoptotic cell death, affording the opportunity to define the
      genetic pathways required for protection from reproductive cell death. We have
      additionally found that the DNA damage response pathway is necessary for
      protection from reproductive cell death, supporting the long-held tenet that DNA
      damage is the cause of reproductive cell death and further validating this model.
      This genetic tissue model provides a valuable tool for oncology-based research
      and affords a platform to broaden our insight into responses to cytotoxic therapy
      in tissues.

PMID- 16788065
TI  - The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori
      strain: evolution during disease progression.
AB  - Helicobacter pylori produces acute superficial gastritis in nearly all of its
      human hosts. However, a subset of individuals develops chronic atrophic gastritis
      (ChAG), a condition characterized in part by diminished numbers of acid-producing
      parietal cells and increased risk for development of gastric adenocarcinoma.
      Previously, we used a gnotobiotic transgenic mouse model with an engineered
      ablation of parietal cells to show that loss of parietal cells provides an
      opportunity for a H. pylori isolate from a patient with ChAG (HPAG1) to bind to,
      enter, and persist within gastric stem cells. This finding raises the question of
      how ChAG influences H. pylori genome evolution, physiology, and tumorigenesis.
      Here we describe the 1,596,366-bp HPAG1 genome. Custom HPAG1 Affymetrix
      GeneChips, representing 99.6% of its predicted ORFs, were used for whole-genome
      genotyping of additional H. pylori ChAG isolates obtained from Swedish patients
      enrolled in a case-control study of gastric cancer, as well as ChAG- and cancer
      associated isolates from an individual who progressed from ChAG to gastric
      adenocarcinoma. The results reveal a shared gene signature among ChAG strains, as
      well as genes that may have been lost or gained during progression to
      adenocarcinoma. Whole-genome transcriptional profiling of HPAG1's response to
      acid during in vitro growth indicates that genes encoding components of metal
      uptake and utilization pathways, outer membrane proteins, and virulence factors
      are among those associated with H. pylori's adaptation to ChAG.

PMID- 16788066
TI  - H2AX phosphorylation within the G1 phase after UV irradiation depends on
      nucleotide excision repair and not DNA double-strand breaks.
AB  - The variant histone H2AX is phosphorylated in response to UV irradiation of
      primary human fibroblasts in a complex fashion that is radically different from
      that commonly reported after DNA double-strand breaks. H2AX phosphorylation after
      exposure to ionizing radiation produces foci, which are detectable by
      immunofluorescence microscopy and have been adopted as clear and consistent
      quantitative markers for DNA double-strand breaks. Here we show that in contrast
      to ionizing radiation, UV irradiation mainly induces H2AX phosphorylation as a
      diffuse, even, pan-nuclear staining. UV induced pan-nuclear phosphorylation of
      H2AX is present in all phases of the cell cycle and is highest in S phase. H2AX
      phosphorylation in G(1) cells depends on nucleotide excision repair factors that
      may expose the S-139 site to kinase activity, is not due to DNA double-strand
      breaks, and plays a larger role in UV-induced signal transduction than previously
      realized.

PMID- 16788068
TI  - Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin
      protein Sin1p/Spt2p.
AB  - The yeast chromatin protein Sin1p/Spt2p has long been studied, but the
      understanding of its function has remained elusive. The protein has sequence
      similarity to HMG1, specifically binds crossing DNA structures, and serves as a
      negative transcriptional regulator of a small family of genes that are activated
      by the SWI/SNF chromatin-remodeling complex. Recently, it has been implicated in
      maintaining the integrity of chromatin during transcription elongation. Here we
      present experiments whose results indicate that Sin1p/Spt2 is required for, and
      is directly involved in, the efficient recruitment of the mRNA
      cleavage/polyadenylation complex. This conclusion is based on the following
      findings: Sin1p/Spt2 frequently binds specifically downstream of many ORFs but
      almost always upstream of the first polyadenylation site. It directly interacts
      with Fir1p, a component of the cleavage/polyadenylation complex. Disruption of
      Sin1p/Spt2p results in foreshortened poly(A) tracts on mRNA. It is synthetically
      lethal with Cdc73p, which is involved in the recruitment of the complex. This
      report shows that a chromatin component is involved in 3' end processing of RNA.

PMID- 16788067
TI  - Functional conservation of cold shock domains in bacteria and higher plants.
AB  - In Escherichia coli, a family of cold shock proteins (CSPs) function as
      transcription antiterminators or translational enhancers at low temperature by
      destabilizing RNA secondary structure. A wheat nucleic acid-binding protein
      (WCSP1) was found to contain a cold shock domain (CSD) bearing high similarity to
      E. coli cold shock proteins. In the present study, a series of mutations were
      introduced into WCSP1, and its functionality was investigated by using in vivo
      and in vitro assays in the context of functional conservation with E. coli CSPs.
      Constitutive expression of WT WCSP1 in an E. coli cspA, cspB, cspE, cspG
      quadruple deletion mutant complemented its cold-sensitive phenotype, suggesting
      that WCSP1 shares a function with E. coli CSPs for cold adaptation. In addition,
      transcription antitermination activity was demonstrated for WCSP1 by using an E.
      coli strain that has a hairpin loop upstream of a chloramphenicol resistance
      gene. In vitro dsDNA melting assays clearly demonstrated that WCSP1 melts dsDNA,
      an activity that was positively correlated to the ability to bind ssDNA. When
      mutations were introduced at critical residues within the consensus RNA binding
      motifs (RNP1 and RNP2) of WCSP1, it failed to melt dsDNA. Studies with WCSP1-GFP
      fusion proteins documented patterns that are consistent with ER and nuclear
      localization. In vivo and in vitro functional analyses, coupled with subcellular
      localization data, suggest that WCSP1 may function as a RNA chaperone to
      destabilize secondary structure and is involved in the regulation of translation
      under low temperature.

PMID- 16788069
TI  - How photosynthetic reaction centers control oxidation power in chlorophyll pairs
      P680, P700, and P870.
AB  - At the heart of photosynthetic reaction centers (RCs) are pairs of chlorophyll a
      (Chla), P700 in photosystem I (PSI) and P680 in photosystem II (PSII) of
      cyanobacteria, algae, or plants, and a pair of bacteriochlorophyll a (BChla),
      P870 in purple bacterial RCs (PbRCs). These pairs differ greatly in their redox
      potentials for one-electron oxidation, E(m). For P680, E(m) is 1,100-1,200 mV,
      but for P700 and P870, E(m) is only 500 mV. Calculations with the linearized
      Poisson-Boltzmann equation reproduce these measured E(m) differences
      successfully. Analyzing the origin for these differences, we found as major
      factors in PSII the unique Mn(4)Ca cluster (relative to PSI and PbRC), the
      position of P680 close to the luminal edge of transmembrane alpha-helix d
      (relative to PSI), local variations in the cd loop (relative to PbRC), and the
      intrinsically higher E(m) of Chla compared with BChla (relative to PbRC).

PMID- 16788070
TI  - Nonvisual light responses in the Rpe65 knockout mouse: rod loss restores
      sensitivity to the melanopsin system.
AB  - Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the
      photopigment melanopsin (OPN4), together with rods and cones, provide light
      information driving nonvisual light responses. We examined nonvisual
      photoreception in mice lacking RPE65, a protein that is required for regeneration
      of visual chromophore in rods and cones. Although Rpe65 knockouts retain a small
      degree of rod function, we show here that circadian phase shifting responses in
      Rpe65(-/-) mice are attenuated far beyond what has been reported for
      rodless/coneless mice. Furthermore, the number of melanopsin-immunoreactive
      perikarya and the extent of dendritic arborizations were decreased in Rpe65
      knockout mice compared with controls. To assess the nature of the photoreceptive
      defect in Rpe65 null mice, we eliminated either rods or melanopsin from Rpe65(-/
      ) retinas by generating (i) Rpe65(-/-) mice carrying a transgene (rdta) that
      results in selective elimination of rods and (ii) double knockout Rpe65(-/
      );Opn4(-/-) mice. Surprisingly, rod loss in Rpe65 knockout mice resulted in
      restoration of circadian photosensitivity. Normal photoentrainment was lost in
      Rpe65(-/-);Opn4(-/-) mice, and, instead, a diurnal phenotype was observed. Our
      findings demonstrate that RPE65 is not required for ipRGC function but reveal the
      existence of a mechanism whereby rods may influence the function of ipRGCs.

PMID- 16788071
TI  - Inner retinal photoreception independent of the visual retinoid cycle.
AB  - Mice lacking the visual cycle enzymes RPE65 or lecithin-retinol acyl transferase
      (Lrat) have pupillary light responses (PLR) that are less sensitive than those of
      mice with outer retinal degeneration (rd/rd or rdta). Inner retinal
      photoresponses are mediated by melanopsin-expressing, intrinsically
      photosensitive retinal ganglion cells (ipRGCs), suggesting that the melanopsin
      dependent photocycle utilizes RPE65 and Lrat. To test this hypothesis, we
      generated rpe65(-/-); rdta and lrat(-/-); rd/rd mutant mice. Unexpectedly, both
      rpe65(-/-); rdta and lrat(-/-); rd/rd mice demonstrate paradoxically increased
      PLR photosensitivity compared with mice mutant in visual cycle enzymes alone.
      Acute pharmacologic inhibition of the visual cycle of melanopsin-deficient mice
      with all-trans-retinylamine results in a near-total loss of PLR sensitivity,
      whereas treatment of rd/rd mice has no effect, demonstrating that the inner
      retina does not require the visual cycle. Treatment of rpe65(-/-); rdta with 9
      cis-retinal partially restores PLR sensitivity. Photic sensitivity in P8 rpe65(-/
      ) and lrat(-/-) ipRGCs is intact as measured by ex vivo multielectrode array
      recording. These results demonstrate that the melanopsin-dependent ipRGC
      photocycle is independent of the visual retinoid cycle.

PMID- 16788072
TI  - Long-range cooperative binding effects in a T cell receptor variable domain.
AB  - Although cellular processes depend on protein-protein interactions, our
      understanding of molecular recognition between proteins remains far from
      comprehensive. Protein-protein interfaces are structural and energetic mosaics in
      which a subset of interfacial residues, called hot spots, contributes
      disproportionately to the affinity of the complex. These hot-spot residues can be
      further clustered into hot regions. It has been proposed that binding energetics
      between residues within a hot region are cooperative, whereas those between hot
      regions are strictly additive. If this idea held true for all protein-protein
      interactions, then energetically significant long-range conformational effects
      would be unlikely to occur. In the present study, we show cooperative binding
      energetics between distinct hot regions that are separated by >20 A. Using
      combinatorial mutagenesis and surface plasmon resonance binding analysis to
      dissect additivity and cooperativity in a complex formed between a variable
      domain of a T cell receptor and a bacterial superantigen, we find that
      combinations of mutations from each of two hot regions exhibited significant
      cooperative energetics. Their connecting sequence is composed primarily of a
      single beta-strand of the T cell receptor variable Ig domain, which has been
      observed to undergo a strand-switching event and does not form an integral part
      of the stabilizing core of this Ig domain. We propose that these cooperative
      effects are propagated through a dynamic structural network. Cooperativity
      between hot regions has significant implications for the prediction and
      inhibition of protein-protein interactions.

PMID- 16788073
TI  - Regulation of large dense-core vesicle volume and neurotransmitter content
      mediated by adaptor protein 3.
AB  - Adaptor protein 3 (AP-3) is a vesicle-coat protein that forms a heterotetrameric
      complex. Two types of AP-3 subunits are found in mammalian cells. Ubiquitous AP-3
      subunits are expressed in all tissues of the body, including the brain. In
      addition, there are neuronal AP-3 subunits that are thought to serve neuron
      specific functions such as neurotransmitter release. In this study, we show that
      overexpression of neuronal AP-3 in mouse chromaffin cells results in a striking
      decrease in the neurotransmitter content of individual vesicles (quantal size),
      whereas deletion of all AP-3 produces a dramatic increase in quantal size; these
      changes were correlated with alterations in dense-core vesicle size. AP-3 appears
      to localize in the trans-Golgi network and possibly immature secretory vesicles,
      where it may be involved in the formation of neurosecretory vesicles.

PMID- 16788074
TI  - Nociceptin/orphanin FQ presynaptically decreases GABAergic transmission and
      blocks the ethanol-induced increase of GABA release in central amygdala.
AB  - Behavioral studies show that the GABAergic system in the central amygdala (CeA)
      nucleus has a complex role in the reinforcing effects effects of ethanol and the
      anxiogenic response to ethanol withdrawal. Opioid peptides and
      nociceptin/orphanin FQ (nociceptin) within the CeA are implicated also in
      regulating voluntary ethanol consumption and ethanol relapse. Recently, we
      reported that basal GABAergic transmission was increased in ethanol-dependent
      rats, and that acute ethanol increases GABA(A) receptor-mediated inhibitory
      postsynaptic currents (IPSCs) in CeA neurons from both naive and ethanol
      dependent rats to the same extent, suggesting lack of tolerance for the acute
      effect of ethanol. Here, we investigated the effect of nociceptin on IPSCs in CeA
      neurons and its interaction with ethanol effects on these GABA synapses. We found
      that nociceptin moderately decreased IPSC amplitudes, acting mostly
      presynaptically as it increased paired-pulse facilitation ratio of IPSCs and
      decreased miniature IPSC frequencies (but not amplitudes). Nociceptin also
      prevented the ethanol-induced augmentation of IPSCs in CeA of naive rats.
      Interestingly, in CeA of ethanol-dependent rats, the nociceptin-induced
      inhibition of IPSCs was increased, indicating an enhanced sensitivity to
      nociceptin. Nociceptin also blocked the ethanol-induced augmentation of IPSCs in
      ethanol-dependent rats. Our data suggest that nociceptin has a role in regulating
      the GABAergic system and opposing the effect elicited by ethanol. Thus,
      nociceptin may represent a therapeutic target for alleviating alcohol dependence.

PMID- 16788075
TI  - Accuracy, validity and reliability in assessment and in evaluation of services
      for older people: the role of the interRAI MDS assessment system.

PMID- 16788076
TI  - Addressing the health needs of frail elderly people: Ontario's experience with an
      integrated health information system.

PMID- 16788077
TI  - Acetylcholinesterase inhibitors for Alzheimer's disease: anti-inflammatories in
      acetylcholine clothing!
AB  - The pathogenesis of Alzheimer's disease (AD) has been linked to a deficiency in
      the brain neurotransmitter acetylcholine. Subsequently, acetylcholinesterase
      inhibitors (AChEIs) were introduced for the symptomatic treatment of AD. The
      prevailing view has been that the efficacy of AChEIs is attained through their
      augmentation of acetylcholine-medicated neuron to neuron transmission. However,
      AChEIs also protect cells from free radical toxicity and beta-amyloid-induced
      injury, and increased production of antioxidants. In addition, it has been
      reported that AChEIs directly inhibit the release of cytokines from microglia and
      monocytes. These observations are supported by evidence showing a role for
      acetylcholine in suppression of cytokine release through a 'cholinergic anti
      inflammatory pathway'. Based on the accumulating research data so far, it is no
      longer appropriate to consider that the sole action of AChEIs in AD is through
      direct acetylcholine-medicated enhancement of neuronal transmission. Evidence
      points to a possible anti-inflammatory role for these agents as well.

PMID- 16788078
TI  - Intermediate care in England: where next?

PMID- 16788080
TI  - Utilisation of diagnostic computerised tomography imaging and immediate clinical
      outcomes in older people with stroke before and after introduction of the
      National Service Framework for older people. A comparative study of hospital
      based stroke registry data (1997-2003): Norfolk experience.
AB  - INTRODUCTION: how the National Service Framework (NSF) for older people in
      England might be associated with changes in clinically relevant stroke outcome
      has not been investigated. We looked for changes in computerised tomography (CT)
      scan rate, inpatient case-fatality rate (CFR), length of acute hospital stay and
      discharge destination for older people with stroke, compared with their younger
      counterparts, for a period before, and after, the introduction of the NSF.
      METHODS: two periods, 4 years before and 2 years after the publication of the
      NSF, were selected to compare the above outcomes between three age categories: <
      65, 65-84 and > or = 85 years of age. Annual summary data for these periods were
      compared for the magnitude of changes in all age categories for all outcomes
      measured between pre- and post-NSF periods. RESULTS: n = 5,219. Utilisation of CT
      imaging had increased in all age groups post-NSF, with the most significant
      improvement in the oldest group. This change was associated with a greater
      proportion of people who had CT in this age group being discharged home in the
      post-NSF period. There was no change in the mortality from stroke in any age
      group during the study. Although the length of acute hospital stay increased,
      this was associated with a higher percentage of home discharges particularly in >
      65-year olds, suggesting better clinical outcome in those who survived.
      CONCLUSIONS: in this single-centre analysis, the post-NSF period appeared to be
      associated with improvement in outcome in older people with stroke. Continual
      monitoring using stroke registry data may help to assess whether these effects
      are sustained in the longer term.

PMID- 16788079
TI  - Comparative analysis of mortality in patients with Alzheimer's disease treated
      with donepezil or galantamine.
AB  - BACKGROUND: few studies have analysed the effect of the long-term use of
      cholinesterase inhibitors (ChEIs) on mortality. OBJECTIVE: to compare the long
      term effects of galantamine and donepezil treatment on the mortality rate in
      Alzheimer's disease (AD) patients. DESIGN: a retrospective cohort study. SETTING
      AND SUBJECTS: 404 patients referred by primary care centres to a Memory Clinic
      who were diagnosed with probable AD and who were prescribed treatment with
      donepezil or galantamine. METHODS: standardised review of the patient's medical
      records. RESULTS: 14.5% of the patients showed intolerance to the treatment with
      ChEIs during the first 15 days. Of those patients who initially tolerated the
      treatment, 18.5% gave it up after a mean duration of 13.36 months and a mean dose
      of 7.5 mg/day of donepezil or 14.3 mg/day of galantamine. The mean duration of
      the treatment in patients who did not abandon the treatment was 25.4 months and
      the mean dose was 8.1 mg/day of donepezil or 20.0 mg/day of galantamine. There
      were no differences in the mortality rate between patients treated with donepezil
      or galantamine (13.7 versus 12.2; P = 0.75). The multivariate analysis through
      binary logistic regression showed that the variables associated with mortality
      were male gender, older age, heart failure, treatment with antipsychotic drugs
      and a high score on the Global Deterioration Scale. CONCLUSIONS: the duration and
      the dose of donepezil or galantamine are not related to an increase in mortality.
      The related variables were advanced age, the severity of the dementia, being
      male, heart failure and treatment with antipsychotic drugs.

PMID- 16788081
TI  - Audits of medication use in Sydney nursing homes.
AB  - BACKGROUND: most nursing home residents take several different medications.
      Reports have shown considerable variation in the frequency and types of
      prescriptions between nursing homes and between countries. OBJECTIVE: to record
      the current pattern of medication use in Sydney nursing homes to allow comparison
      with patterns observed 5 and 10 years previously, and in other countries.
      METHODS: data were recorded from the medication cards and clinical files of all
      3,054 residents in 50 nursing homes in the Central Sydney Health Area and were
      compared with data recorded in 1993 and 1998. RESULTS: the mean number of
      medications prescribed per resident in 2003 was 6.84, while the mean number
      consumed regularly (rather than 'as necessary') was 5.42. These numbers were
      higher than 5 and 10 years previously, though there had been reductions in use of
      diuretics, anticonvulsants, hypnotics and anxiolytics. There had been increased
      prescription of antidepressants, anti-diabetes drugs, calcium and (among women)
      thyroid hormones. Prescription rates for laxatives, cardiovascular medication and
      analgesics remained high. CONCLUSIONS: the pattern of medication prescription has
      changed. This may be attributable to improved education of clinicians and nursing
      home staff, involvement of pharmacists and altered or increased prevalence of
      medical and mental disorders in nursing homes.

PMID- 16788082
TI  - Personality and incident disability in older persons.
AB  - OBJECTIVE: to examine the relation of personality to the development of
      disability in old age. METHODS: participants are 813 older Catholic nuns, priests
      and brothers without dementia or disability at study onset. As part of a uniform
      baseline evaluation, they completed standard measures of the five principal
      dimensions of personality. Disability was assessed at baseline and annually
      thereafter with the Katz scale. The relation of each trait to incident disability
      was assessed in proportional hazard models controlled for age, sex, education and
      selected clinical variables. RESULTS: during a mean of about 6 years of
      observation, 255 persons (31%) became dependent on at least one activity of daily
      living. Risk of becoming disabled was 85% [95% confidence interval (CI) = 80.5
      89.6%] lower in persons with high (90th percentile) compared to low (10th
      percentile) extraversion and 50% (95% CI = 46.6-54.2%) lower in those with high
      compared to low conscientiousness, and controlling for chronic medical
      conditions, depressive symptoms or social and cognitive activity did not
      substantially affect these associations. By contrast, neuroticism had a marginal
      association with disability risk that was eliminated after controlling for
      depressive symptomatology, and openness and agreeableness were unrelated to
      disability risk. CONCLUSIONS: The results suggest that higher levels of
      extraversion and conscientiousness may be associated with a reduced risk of
      incident disability in old age.

PMID- 16788083
TI  - Atishoo! Atishoo! we all fall down!
AB  - We report the unusual case of an elderly lady with glaucoma and sneeze syncope
      because of transient complete atrioventricular block, who had resolution of
      syncopal and pre-syncopal symptoms following removal of her beta-blocker
      eyedrops. This case suggests a previously unrecognised pathophysiology in sneeze
      syncope and illustrates the potential problems associated with the systemic
      absorption of beta-blocker eyedrops as well as the ingenuity of older patients
      when participating in the investigation of their own illnesses.

PMID- 16788084
TI  - Niacin toxicity: a rare presentation mimicking malignancy.

PMID- 16788085
TI  - Adult pyloric stenosis-a forgotten entity.

PMID- 16788086
TI  - Differences in end of life care in patients who died with dementia during acute
      hospital admissions.

PMID- 16788088
TI  - Motor inhibition and learning impairments in school-aged children following
      exposure to organophosphate pesticides in infancy.
AB  - Despite the critical role of acetylcholinesterase (AChE) in cortical function and
      development, no long-term studies have been conducted in humans on the long-term
      sequelae of the disruption of the cholinergic system in early childhood. We
      report a neuropsychological assessment of healthy school-aged children, who had
      been hospitalized in infancy following exposure to organophosphate pesticides,
      compared with children exposed to other toxins such as kerosene, and age- and sex
      matched non-exposed children. Although overall, the children seem to have
      overcome the acute one-time exposure incident, and they all attend regular
      schools, a finer assessment of specific cognitive abilities indicates they are
      impaired compared with the matched controls. Specifically, the children who had
      been exposed to organophosphate pesticides had a deficit in inhibitory motor
      control. Children with pesticide or kerosene poisoning had a retrieval deficit on
      the acquisition phase of a verbal learning task.

PMID- 16788089
TI  - Boswellic acids stimulate arachidonic acid release and 12-lipoxygenase activity
      in human platelets independent of Ca2+ and differentially interact with platelet
      type 12-lipoxygenase.
AB  - Boswellic acids inhibit the transformation of arachidonic acid to leukotrienes
      via 5-lipoxygenase but can also enhance the liberation of arachidonic acid in
      human leukocytes and platelets. Using human platelets, we explored the molecular
      mechanisms underlying the boswellic acid-induced release of arachidonic acid and
      the subsequent metabolism by platelet-type 12-li-poxygenase (p12-LO). Both beta
      boswellic acid and 3-O-acetyl-11-keto-boswellic acid (AKBA) markedly enhanced the
      release of arachidonic acid via cytosolic phospholipase A2 (cPLA2), whereas for
      generation of 12-hydro(pero)xyeicosatetraenoic acid [12-H(P)ETE], AKBA was less
      potent than beta-boswellic acid and was without effect at higher concentrations
      (> or =30 microM). In contrast to thrombin, beta-boswellic acid-induced release
      of ara-chidonic acid and formation of 12-H(P)ETE was more rapid and occurred in
      the absence of Ca2+. The Ca2+-independent release of arachidonic acid and 12
      H(P)ETE production elicited by beta-boswellic acid was not affected by
      pharmacological inhibitors of signaling molecules relevant for agonist-induced
      arachidonic acid liberation and metabolism. It is noteworthy that in cell-free
      assays, beta-boswellic acid increased p12-LO catalysis approximately 2-fold in
      the absence but not in the presence of Ca2+, whereas AKBA inhibited p12-LO
      activity. No direct modulatory effects of boswellic acids on cPLA2 activity in
      cell-free assays were evident. Therefore, immobilized KBA (linked to Sepharose
      beads) selectively precipitated p12-LO from platelet lysates but failed to bind
      cPLA2. Taken together, we show that boswellic acids induce the release of
      arachidonic acid and the synthesis of 12-H(P)ETE in human platelets by unique
      Ca2+-independent routes, and we identified p12-LO as a selective molecular target
      of boswellic acids.

PMID- 16788090
TI  - Regulation of the CYP1A1 gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin but not by
      beta-naphthoflavone or 3-methylcholanthrene is altered in hepatitis C virus
      replicon-expressing cells.
AB  - Exposure to hepatitis C virus (HCV) can lead to the development of cirrhosis and
      hepatocellular carcinoma. To examine the effects of long-term HCV infection on
      hepatic cytochrome P450 1A1 (CYP1A1) expression and function, we used a human
      hepatoma cell line expressing the HCV subgenomic replicon (Huh.8) to evaluate
      CYP1A1 induction by the aryl hydrocarbon receptor (AhR) ligand, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). In this study, we demonstrate that the
      induction of CYP1A1 expression in Huh.8 cells by TCDD but not by beta
      naphthoflavone or 3-methylcholanthrene was significantly diminished. TCDD
      exposure of Huh.8 cells resulted in greater than 55% suppression of CYP1A1
      transcription compared with the parent cell line Huh7, whereas protein levels and
      enzyme activities were further diminished. Suppression of CYP1A1 mRNA expression
      in TCDD-treated Huh.8 cells was partially reversed after pretreatment with the
      antioxidants N-acetylcysteine and nordihydroguaiaretic acid, suggesting a role
      for oxidative stress. Induced CYP1A1 message, protein, and enzyme activity were
      partially restored in an Huh7 cell line expressing the HCV replicon containing a
      deletion in the nonstructural protein NS5A. Furthermore, adenoviral expression of
      NS5A in Huh7 partially suppressed TCDD-induced CYP1A1 protein and enzyme
      activity, implicating this protein in the mechanism of suppression. These
      findings demonstrate that TCDD-mediated AhR signaling is impaired in hepatocytes
      in which HCV is present and that NS5A alone or in the presence of other
      nonstructural proteins of the subgenomic replicon is in part responsible.

PMID- 16788091
TI  - Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'
      adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4
      hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role
      of retinoic acid receptor gamma and retinoid-independent pathways.
AB  - The retinoid-related molecules (RRMs) ST1926 [(E)-3-(4'-hydroxy-3'
      adamantylbiphenyl-4-yl)acrylic acid] and CD437 (6-[3-(1-adamantyl)-4
      hydroxyphenyl]-2-naphthalene carboxylic acid) are promising anticancer agents. We
      compared the retinoic acid receptor (RAR) trans-activating properties of the two
      RRMs and all-trans-retinoic acid (ATRA). ST1926 and CD437 are better RARgamma
      agonists than ATRA. We used three teratocarcinoma cell lines to evaluate the
      significance of RARgamma in the activity of RRMs: F9-wild type (WT); F9gamma-/-,
      lacking the RARgamma gene; F9gamma51, aF9gamma-/-derivative, complemented for the
      RARgamma deficit. Similar to ATRA, ST1926 and CD437 activate cytodifferentiation
      only in F9-WT cells. Unlike ATRA, ST1926 and CD437 arrest cells in the G2/M phase
      of the cell cycle and induce apoptosis in all F9 cell lines. Our data indicate
      that RARgamma and the classic retinoid pathway are not relevant for the
      antiproliferative and apoptotic activities of RRMs in vitro. Increases in
      cytosolic calcium are fundamental for apoptosis, in that intracellular calcium
      chelators abrogate the process. Comparison of the gene expression profiles
      associated with ST1926 and ATRA in F9-WT and F9gamma-/-indicates that the RRM
      activates a conspicuous nonretinoid response in addition to the classic and RAR
      dependent pathway. The pattern of genes regulated by ST1926 selectively, in a
      RARgamma-independent manner, provides novel insights into the possible molecular
      determinants underlying the activity of RRMs in vitro. Furthermore, it suggests
      that RARgamma-dependent responses are relevant to the activity of RRMs in vivo.
      Indeed, the receptor hinders the antitumor activity in vivo, in that both
      syngeneic and immunosuppressed SCID mice bearing F9gamma-/- tumors have increased
      life spans after treatment with ST1926 and CD437 relative to their F9-WT
      counterparts.

PMID- 16788092
TI  - A question of blood, race, and politics.
AB  - This article explores the political and intellectual context of a controversy
      arising from a proposal made at the 1959 meetings of the American Society of
      Blood Banks to divide the blood supply by race. The authors, a group of blood
      bankers and surgeons in New York, outlined difficulties in finding compatible
      blood for transfusion during open-heart surgery, which they attributed to prior
      sensitization of their patient, a Caucasian, by a previous transfusion from an
      African American donor. Examining the statistical distribution of blood-group
      antigens among the various races, they concluded that risk of adverse hemolytic
      reactions and the cost of testing could be reduced by establishing separate donor
      pools. The media reported the suggestion, which, given the political climate of
      the day, rapidly became a public issue involving geneticists, blood-bankers,
      physical anthropologists, and the African American medical community. Liberals
      condemned it, whereas eugenically inclined segregationists used the finding to
      support their views concerning evolutionary distance between the races and the
      dangers of miscegenation. Here we examine the contribution of comparative racial
      serology to this affair, the arguments and background of the main players, and
      the relevance of the debate to discussions about the role of "race" in post
      genomic medicine.

PMID- 16788093
TI  - Fondaparinux for thromboembolic treatment and prophylaxis of heparin-induced
      thrombocytopenia.
AB  - OBJECTIVE: To review literature evaluating the use of fondaparinux for
      thromboembolic treatment and prophylaxis in patients with heparin-induced
      thrombocytopenia (HIT). DATA SOURCES: A MEDLINE search (1966-February 2006) was
      conducted using the search terms fondaparinux, heparin, low-molecular-weight
      heparin, and thrombocytopenia to identify English-language articles. Additional
      sources were identified from bibliographies of select articles and the
      manufacturer. DATA SYNTHESIS: Fondaparinux, a pentasaccharide that selectively
      inhibits factor Xa, has been reported to have negligible or no cross-reactivity
      in vitro with HIT antibodies. Thromboembolic treatment and prophylaxis with
      fondaparinux in patients with HIT has been described. Three cases reported
      patients who were successfully treated for thromboembolic events with
      fondaparinux after developing HIT during therapy with unfractionated heparin
      (UFH) or low-molecular-weight heparin (LMWH). Another report showed positive
      outcomes using fondaparinux for prophylaxis in a patient who had previously
      developed HIT after receiving UFH. Moreover, 2 case series, one using
      fondaparinux for prophylaxis in patients with a previous diagnosis of HIT and the
      other using fondaparinux for treatment in patients who developed HIT while
      receiving UFH or LMWH, reported normal platelet counts during fondaparinux
      treatment. Finally, results of a retrospective review demonstrated that
      fondaparinux prevented thromboembolic events or recurrent thrombocytopenia in
      patients with a prior HIT diagnosis. CONCLUSIONS: Limited data support the use of
      fondaparinux for thromboembolic treatment or prophylaxis in patients with
      antibody assay-confirmed HIT who do not have a contraindication for fondaparinux
      use. Randomized controlled trials have not been published; therefore, questions
      remain regarding efficacy, safety, optimal doses, treatment duration, and
      incidence of thromboembolic events when fondaparinux is used in this setting.
      Prospective trials evaluating the efficacy and safety of fondaparinux in this
      patient population need to be conducted to answer these questions.

PMID- 16788094
TI  - Tipranavir: a protease inhibitor for HIV salvage therapy.
AB  - OBJECTIVE: To review the efficacy, safety, pharmacology, virology,
      pharmacokinetics, and resistance of the nonpeptidic protease inhibitor (PI)
      tipranavir. DATA SOURCES AND STUDY SELECTION: A PubMed search (1966-February
      2006) was conducted using the key words tipranavir or PNU-140690, with the
      limitation of English-language reports. Pharmacokinetic and randomized clinical
      trials originating from major HIV conferences, such as the Conference on
      Retroviruses and Opportunistic Infections, International AIDS Society, European
      AIDS Conference, and Interscience Conference on Antimicrobial Agents and
      Chemotherapy, published only in abstract form, from 2000 to February 2006, were
      reviewed for relevance and included in this review. DATA SYNTHESIS: Phase III
      studies have shown that tipranavir is effective in the treatment of PI-resistant
      HIV compared with other PI-containing regimens. Adverse effects associated with
      tipranavir/ritonavir therapy include gastrointestinal reactions, hepatotoxicity,
      and elevations in cholesterol and triglyceride levels. Resistance data suggest
      that tipranavir/ritonavir should be reserved for salvage therapy in
      antiretroviral-experienced patients who have previously failed standard PI
      therapies. The potential for hepatotoxicity and drug interactions and the expense
      of tipranavir due to required ritonavir boosting may limit its widespread use.
      CONCLUSIONS: Tipranavir/ritonavir is an essential addition to the antiretroviral
      armamentarium for HIV-infected patients with limited treatment options.

PMID- 16788096
TI  - Hypogammaglobulinemia and exacerbated CD8 T-cell-mediated immunopathology in SAP
      deficient mice with chronic LCMV infection mimics human XLP disease.
AB  - The human genetic disease X-linked lymphoproliferative disease (XLP), which is
      caused by mutations in SH2D1A/SAP that encode SLAM-associated protein (SAP), is
      characterized by an inability to control Epstein-Barr virus (EBV) and
      hypogammaglobulinemia. It is unclear which aspects of XLP disease are specific to
      herpesvirus infection and which reflect general immunologic functions performed
      by SAP. We examined SAP- mice during a chronic LCMV infection, specifically to
      address the following question: Which SAP deficiency immunologic problems are
      general, and which are EBV specific? Illness, weight loss, and prolonged viral
      replication were much more severe in SAP- mice. Aggressive immunopathology was
      observed. This inability to control chronic LCMV was associated with both CD8 T
      cell and B-cell response defects. Importantly, we demonstrate that SAP- CD8 T
      cells are the primary cause of the immunopathology and clinical illness, because
      depletion of CD8 T cells blocked disease. This is the first direct demonstration
      of SAP- CD8 T-cell-mediated immunopathology, confirming 30 years of XLP clinical
      observations and indirect experimentation. In addition, germinal center formation
      was extremely defective in chronically infected SAP- animals, and
      hypogammaglobulinemia was observed. These findings in a chronic viral infection
      mouse model recapitulate key features of human XLP and clarify SAP's critical
      role regulating both cellular and humoral immunity.

PMID- 16788095
TI  - Dysregulation of IL-15-mediated T-cell homeostasis in TGF-beta dominant-negative
      receptor transgenic mice.
AB  - T-cell subpopulations, defined by their expression of CD4, CD8, naive, and memory
      cell-surface markers, occupy distinct homeostatic compartments that are regulated
      primarily by cytokines. CD8+ memory T cells, as defined by CD44(hi) surface
      expression, are dependent on IL-15 as a positive regulator of their homeostatic
      maintenance. Manipulation of IL-15 signaling through gene aberration,
      overexpression, or receptor alterations has been shown to dramatically affect T
      cell homeostasis, with overexpression leading to fatal leukemia. Here we show
      that TGF-beta is the critical negative regulator of murine CD8+ memory T-cell
      homeostasis with direct opposition to the positive effects of IL-15. This
      negative regulation is mediated, at least in part, by the ability of TGF-beta to
      modulate expression of the beta-chain of the IL-15 receptor, thus establishing a
      central axis between these 2 cytokines for homeostatic control of CD8+ memory T
      cell populations. These data establish TGF-beta as a critical and dominant tumor
      suppressor pathway opposing IL-15-mediated CD8+ T-cell expansion and potential
      malignant transformation.

PMID- 16788097
TI  - Host B cells produce IL-10 following TBI and attenuate acute GVHD after
      allogeneic bone marrow transplantation.
AB  - Host antigen-presenting cells (APCs) are known to be critical for the induction
      of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation
      (BMT), but the relative contribution of specific APC subsets remains unclear. We
      have studied the role of host B cells in GVHD by using B-cell-deficient microMT
      mice as BMT recipients in a model of CD4-dependent GVHD to major
      histocompatibility complex antigens. We demonstrate that acute GVHD is initially
      augmented in microMT recipients relative to wild-type recipients (mortality: 85%
      vs 44%, P < .01), and this is the result of an increase in donor T-cell
      proliferation, expansion, and inflammatory cytokine production early after BMT.
      Recipient B cells were depleted 28-fold at the time of BMT by total body
      irradiation (TBI) administered 24 hours earlier, and we demonstrate that TBI
      rapidly induces sustained interleukin-10 (IL-10) generation from B cells but not
      dendritic cells (DCs) or other cellular populations within the spleen. Finally,
      recipient mice in which B cells are unable to produce IL-10 due to homologous
      gene deletion develop more severe acute GVHD than recipient mice in which B cells
      are wild type. Thus, the induction of IL-10 in host B cells during conditioning
      attenuates experimental acute GVHD.

PMID- 16788098
TI  - Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated
      gene delivery to hepatocytes.
AB  - Upon local delivery, adenovirus (Ad) serotype 5 viruses use the coxsackie and Ad
      receptor (CAR) for cell binding and alpha(v) integrins for internalization. When
      administered systemically, however, their role in liver tropism is limited
      because CAR-permissive and mutated viruses show similar biodistribution, a
      finding recently attributed to blood coagulation factor (F) IX or complement
      protein C4BP binding to the adenovirus fiber and "bridging" to either low-density
      lipoprotein receptor-related protein or heparan sulfate proteoglycans. Here, we
      show that hepatocyte transduction in vitro can be enhanced by the vitamin K
      dependent factors FX, protein C, and FVII in addition to FIX but not by
      prothrombin (FII), FXI, and FXII. This phenomenon was not dependent on
      proteolytic activation or cell signaling activity and for FX was mediated by
      direct virus-factor binding. Human FX substantially enhanced hepatocyte
      transduction by CAR-permissive and mutated viruses in an ex vivo liver perfusion
      model. In vivo, global down-regulation of vitamin K-dependent zymogens by
      warfarin significantly diminished liver uptake of CAR-deleted Ads; however, this
      phenomenon was fully rescued by acute infusion of human FX. Our results indicate
      a common and pivotal role for distinct vitamin K-dependent coagulation factors in
      mediating hepatocyte transduction by adenoviruses in vitro and in vivo.

PMID- 16788099
TI  - c-Myc mediates pre-TCR-induced proliferation but not developmental progression.
AB  - Constitutive and cell-autonomous signals emanating from the pre-T-cell receptor
      (pre-TCR) promote proliferation, survival and differentiation of immature
      thymocytes. We show here that induction of pre-TCR signaling resulted in rapid
      elevation of c-Myc protein levels. Cre-mediated thymocyte-specific ablation of c
      Myc in CD25(+)CD44(-) thymocytes reduced proliferation and cell growth at the pre
      TCR checkpoint, resulting in thymic hypocellularity and a severe reduction in
      CD4(+)CD8(+) thymocytes. In contrast, c-Myc deficiency did not inhibit pre-TCR
      mediated differentiation or survival. Myc(-/-) double-negative (DN) 3 cells
      progressed to the double-positive (DP) stage and up-regulated TCRalphabeta
      surface expression in the absence of cell proliferation, in vivo as well as in
      vitro. These observations indicate that distinct signals downstream of the pre
      TCR are responsible for proliferation versus differentiation, and demonstrate
      that c-Myc is only required for pre-TCR-induced proliferation but is dispensable
      for developmental progression from the DN to the DP stage.

PMID- 16788100
TI  - Impact of chronic graft-versus-host disease on the health status of hematopoietic
      cell transplantation survivors: a report from the Bone Marrow Transplant Survivor
      Study.
AB  - The aim of this study was to understand the impact of chronic graft-versus-host
      disease (cGVHD) on the overall health status of hematopoietic cell
      transplantation (HCT) survivors. Subjects included 584 individuals who had
      undergone allogeneic HCT between 1976 and 1999, survived 2 or more years, and
      completed a 255-item health questionnaire. Global assessment of health status was
      facilitated by measurement of 6 health status domains: general health, mental
      health, functional impairment, activity limitation, pain, and anxiety/fear.
      Information regarding diagnosis of cGVHD was abstracted from medical records, and
      presence of active cGVHD in the preceding 12 months was self-reported. The
      incidence of cGVHD in participants was 54%, of whom 46% reported active cGVHD. In
      multivariable analyses, subjects with active cGVHD were more likely to report
      adverse general health, mental health, functional impairments, activity
      limitation, and pain than were those with no history of cGVHD. However, health
      status did not differ between those with resolved cGVHD and those who never had
      cGVHD. We conclude that active cGVHD has a significant impact on many aspects of
      the overall health status of HCT survivors and that, most importantly, those
      successfully treated for cGVHD do not appear to have long-term impairments.

PMID- 16788101
TI  - CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans
      retinoic acid in therapy but differ in their antileukemic activities.
AB  - CCAAT/enhancer binding proteins (C/EBPs) play critical roles in myelopoiesis.
      Dysregulation of these proteins likely contributes to the pathogenesis of myeloid
      disorders characterized by a block in granulopoiesis. In one such disease, acute
      promyelocytic leukemia (APL), a promyelocytic leukemia-retinoic acid receptor
      alpha (PML-RARalpha) fusion protein is expressed as a result of a t(15;17)
      chromosomal translocation. Treatment of PML-RARalpha leukemic cells with all
      trans retinoic acid (ATRA) causes them to differentiate into mature neutrophils,
      an effect thought to be mediated by C/EBPs. In this study, we assess the
      potential for cooperativity between increased C/EBP activity and ATRA therapy. We
      demonstrate that although both C/EBPalpha and C/EBPepsilon can significantly
      prolong survival in a mouse model of APL, they are not functionally equivalent in
      this capacity. We also show that forced expression of C/EBPalpha or C/EBPepsilon
      in combination with ATRA treatment has a synergistic effect on survival of
      leukemic mice compared with either therapy alone.

PMID- 16788102
TI  - Differentially methylated alleles in a distinct region of the human interleukin
      1alpha promoter are associated with allele-specific expression of IL-1alpha in
      CD4+ T cells.
AB  - Cytokine secretion profiles of activated T cells are critical for maintaining the
      immunologic balance between protection and tolerance. In mice, several cytokines
      have been reported to exhibit monoallelic expression. Previously, we found that
      the human interleukin-1 alpha (IL1A) gene exhibits a stable allele-specific
      expression pattern in CD4+ T-cell clones. We investigated whether DNA methylation
      is involved in the allele-specific expression of IL-1alpha. Here, we show that
      differential methylation of CpGs in the proximal promoter region is associated
      with allele-specific expression of IL-1alpha in CD4+ T cells. The differential
      methylation pattern is already observed in naive T cells. In keratinocytes, which
      constitutively produce IL-1alpha, the proximal promoter is hypomethylated. CpGs
      located further upstream and in intron 4 were almost all methylated, irrespective
      of expression. Treatment of nonexpressing cells and of T-cell clones with 5-aza
      2'deoxycytidine induced IL-1alpha expression in the nonexpressing cells and
      induced expression of the formerly silent allele in T-cell clones. In addition,
      electrophoretic mobility shift assays showed that methylation of CpGs in the
      proximal promoter resulted in direct inhibition of binding of nuclear factor(s).
      Taken together, these results suggest that allele-specific expression of IL
      1alpha in CD4+ cells is achieved, at least in part, by differential methylation
      of the promoter.

PMID- 16788104
TI  - The metastasis-associated 67-kDa laminin receptor is involved in G-CSF-induced
      hematopoietic stem cell mobilization.
AB  - The 67-kDa laminin receptor (67LR) is a nonintegrin cell-surface receptor with
      high affinity for laminin, which plays a key role in tumor invasion and
      metastasis. We investigated the role of 67LR in granulocyte colony-stimulating
      factor (G-CSF)-induced mobilization of CD34+ hematopoietic stem cells (HSCs) from
      35 healthy donors. G-CSF-mobilized HSCs, including CD34+/CD38- cells, showed
      increased 67LR expression as compared with unstimulated marrow HSCs; noteworthy,
      also, is the fact that the level of 67LR expression in G-CSF-mobilized HSCs
      correlated significantly with mobilization efficiency. During G-CSF-induced HSC
      mobilization, the expression of laminin receptors switched from alpha6 integrins,
      which mediated laminin-dependent adhesion of steady-state human marrow HSCs, to
      67LR, responsible for G-CSF-mobilized HSC adhesion and migration toward laminin.
      In vitro G-CSF treatment, alone or combined with exposure to marrow-derived
      endothelial cells, induced 67LR up-regulation in marrow HSCs; moreover, anti-67LR
      antibodies significantly inhibited transendothelial migration of G-CSF-stimulated
      marrow HSCs. Finally, G-CSF-induced mobilization in mice was associated with 67LR
      up-regulation both in circulating and marrow CD34+ cells, and anti-67LR
      antibodies significantly reduced HSC mobilization, providing the first in vivo
      evidence for 67LR involvement in stem-cell egress from bone marrow after G-CSF
      administration. In conclusion, 67LR up-regulation in G-CSF-mobilized HSCs
      correlates with their successful mobilization and reflects its increase in marrow
      HSCs, which contributes to the egress from bone marrow by mediating laminin
      dependent cell adhesion and transendothelial migration.

PMID- 16788105
TI  - Competent independent driving as an archetypal task of adolescence.
AB  - Supplement Editor, Dr Flaura K Winston, and Co-Editor, Dr Teresa Senserrick,
      introduce 10 papers covering the current science of safe driving among
      adolescents from the varied viewpoints of an international panel of experts. This
      Expert Panel, convened by the Center for Injury Research and Prevention (formerly
      TraumaLink) at the Children's Hospital of Philadelphia and State Farm Insurance
      Companies(R), working jointly on the Youthful Driver Research Initiative,
      represents a wide range of expertise, thereby providing a broad understanding of
      driving, adolescence, and adolescent driving.

PMID- 16788103
TI  - Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb
      dependent thrombus formation in vivo.
AB  - Botrocetin (bt)-facilitated binding of von Willebrand factor (VWF) to the
      platelet membrane glycoprotein (GP) Ib-IX-V complex on platelets in suspension
      initiates a signaling cascade that causes alphaIIbbeta3 activation and platelet
      aggregation. Previous work has demonstrated that bt/VWF-mediated agglutination
      activates alphaIIbbeta3 and elicits ATP secretion in a thromboxane A2 (TxA2)
      dependent manner. The signaling that results in TxA2 production was shown to be
      initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76, PI3K,
      PLCgamma2, and PKC. Here, we demonstrate that the signaling elicited by GPIb
      mediated agglutination that results in TxA2 production is dependent on Bruton
      tyrosine kinase (Btk). The results demonstrate that Btk is downstream of Lyn,
      Syk, SLP-76, and PI3K; upstream of ERK1/2, PLCgamma2, and PKC; and greatly
      enhances Akt phosphorylation. The relationship(s), if any, between ERK1/2,
      PLCgamma2, and PKC were not elucidated. The requirement for Btk and TxA2 receptor
      function in GPIb-dependent arterial thrombosis was confirmed in vivo by
      characterizing blood flow in ferric chloride-treated mouse carotid arteries.
      These results demonstrate that the Btk family kinase, Tec, cannot provide the
      function(s) missing because of the absence of Btk and that Btk is essential for
      both bt/VWF-mediated agglutination-induced TxA2 production and GPIb-dependent
      stable arterial thrombus formation in vivo.

PMID- 16788106
TI  - Reducing crashes and injuries among young drivers: what kind of prevention should
      we be focusing on?
AB  - Every year, drivers throughout the world are killed or injured in road traffic.
      Young drivers run a greater risk everywhere, and this problem is still largely
      unsolved. Better understanding of the underlying processes could, however, be a
      useful tool in preventive endeavours. To change a young driver's goals behind
      driving and the context in which it is done, a variety of different methods of
      persuasion should be tested. Both "soft" and "hard" methods should be used. For
      example, communication and increased enforcement may be used simultaneously.
      Communication campaigns should highlight the dangers of unsafe behaviour and in
      particular target young males. Communication campaigns that employ persuasive,
      emotional messages are most effective where young drivers are concerned. Research
      shows that attitudes about safety are formed at an early age, long before legal
      driving, and therefore it would also be important to target young adolescents.
      Laws need enforcement to be effective and should target areas of particular risk
      to young drivers. Driver education or communication campaigns cannot be expected
      to radically change a young person's life goals. For that purpose, active
      learning methods that make use of the learner's own experiences have to be
      applied. Special courses for young drivers designed to make individuals conscious
      of their personal tendencies and the type of social context that affects their
      driving behaviour could be helpful, whether offered via the ordinary school
      system or at driving schools.

PMID- 16788108
TI  - Can novice drivers be trained to scan for information that will reduce their
      likelihood of a crash?
AB  - Sixteen year old drivers are involved in 10.3 fatal crashes per 100 million
      vehicle miles, a rate almost double that of 18 year olds and almost eight times
      that of 45-64 year olds, who are the safest group of drivers. Crash rates are
      particularly higher during the first month of licensure and decline rapidly for
      about six months and 1000 miles and then much more slowly for at least two years,
      consistent with a typical learning curve. Research indicates that drivers who
      have their learner's permit or are just newly licensed have particular
      difficulties identifying areas of a scenario from which hidden risks could
      emerge. Standard driver education programs do not appear to address these
      difficulties adequately. This suggests that some alternative form of driver
      training could reduce the crashes, either in the classroom or on the road. A PC
      based program designed to teach drivers to recognize risks early on is shown to
      improve their awareness of hazards, both on an advanced driving simulator and on
      the road.

PMID- 16788107
TI  - Youthfulness, inexperience, and sleep loss: the problems young drivers face and
      those they pose for us.
AB  - Young inexperienced drivers are more likely to be involved in road traffic
      crashes than drivers who are older and more experienced. This paper argues that
      neither age nor inexperience are, in and of themselves, sufficient explanations
      of the association between age, experience, and casualty rates. The aim here is
      to consider what it is about inexperienced young drivers in particular that may
      increase crash risk. Evidence is reviewed showing differential sleep loss among
      different teenage groups, which may relate to recently presented evidence that
      young teenagers are more crash involved than drivers in their early twenties.
      Potential acute and chronic effects of sleep loss among teenagers and young
      adults are described.

PMID- 16788109
TI  - Parent involvement in novice teen driving: a review of the literature.
AB  - Motor vehicle crashes remain elevated among novice teen drivers for at least
      several years after licensure. Licensing policies and driver education are the
      two primary countermeasures employed to decrease young driver crash risks.
      Graduated driver licensing policies have proved to be effective in reducing crash
      rates where evaluated. Driver education is an essential part of teaching teens
      the rules of the road and operating a vehicle, but requires few hours of
      professional driver training, relying mainly on parents to provide most of the
      supervised practice driving teens obtain before independent driving licensure.
      The few studies that have been conducted to increase parent supervised practice
      driving have not shown positive results. Moreover, it is unclear that increases
      in practice would improve independent driving safety. Recent research has shown
      that parent management of the early independent driving experience of novice
      teens improves safety outcomes, and other research has shown that it is possible
      to increase parent management practices. This paper provides a review of the
      literature on parent involvement in supervised practice and independent driving,
      and efforts to increase parental management.

PMID- 16788110
TI  - Social marketing: an overview of approach and effects.
AB  - This paper reviews the applicability of commercial and social marketing to teen
      driving safety. It draws on a wide range of information, including evaluation
      studies of specific programs as well as standards of practice within these two
      professions. Social marketing has been widely applied for more than three decades
      in the fields of public health, environmental protection, and political marketing
      with significant success. The paper attempts to distinguish between the practice
      of commercial marketing, whose goal is profit, and the practice of social
      marketing, whose goal is societal benefit. Issues of sustainability,
      segmentation, differences in behavioral characteristics, and cultural competence
      are discussed with specific examples drawn from the transportation safety
      literature. The paper suggests that social marketing represents a viable
      companion to control and education approaches to behavior change to promote teen
      driving safety.

PMID- 16788112
TI  - Legislative advocacy is key to addressing teen driving deaths.
AB  - The increased crash risk of young, novice drivers, especially in their teenage
      years, has been a growing concern at both the state and federal levels. Teenage
      drivers are involved in fatal crashes at more than double the rate of the rest of
      the population per 100 000 licensed drivers. The best way of stemming these
      losses is to enact laws adopting graduated licensure systems that restrict young,
      novice drivers to conditions that reduce crash risk exposure when they first
      operate motor vehicles and to educate the public on the need for this
      legislation. Legislated teenage driving restrictions involve night-time vehicle
      driving restrictions, prohibitions on other teenage passengers, and the required
      presence of supervising adults. These restrictions are relaxed as teenage drivers
      successfully progress through initial and intermediate stages of graduated
      licensure before being granted unrestricted driver licenses. Unfortunately, many
      states have incomplete graduated licensing systems that need further legislative
      action to raise them to the desirable three-stage system that has been shown
      repeatedly to produce the greatest safety benefits. These state efforts should be
      buttressed by federal legislation that has proved to be crucial in allied driver
      behavioral concerns. Because reducing crash risk involves other strategies,
      stringent enforcement of primary seat belt laws as well as improved motor vehicle
      crash avoidance capabilities and crashworthiness must accompany efforts to reduce
      young driver crash risk.

PMID- 16788111
TI  - Young driver risk factors: successful and unsuccessful approaches for dealing
      with them and an agenda for the future.
AB  - The extent to which various interventions to deal with the young driver crash
      problem have worked are discussed, and promising interventions that should be
      tried are identified. Traditional forms of driver licensing and driver education
      have not worked. Graduated licensing reduces the problem and existing laws need
      to be strengthened. Programs involving parents and police have shown some
      potential to increase compliance with graduated licensing restrictions. Insurer
      discount programs also have potential. In other public health areas,
      comprehensive programs have worked better than those based on single components.
      There are continuing efforts to develop new driver education and training
      programs and methods of delivery that can combine with graduated licensing and
      contribute to reductions in the young driver problem. The most promising
      intervention strategy is likely to be a coordinated community based program in
      states with strong graduated licensing laws as a foundation, involving modern
      education and training techniques, insurance discount programs, and well
      publicized enforcement and education programs featuring parents and police in
      combination, with as much input and participation as possible from the target
      group of young drivers.

PMID- 16788114
TI  - Reducing young driver road trauma: guidance and optimism for the future.
AB  - This paper highlights lessons from each of the Expert Panel papers in the present
      supplement that provide guidance for future research and initiatives. Although
      some shortfalls still remain in our understanding, it is argued that much has
      been learned and we are ready for more translation, implementation, and
      evaluation of multilevel interventions to help reduce young driver road trauma.
      Non-use of restraints, speeding, driving at night and with passengers, and
      fatigue are highlighted as key risk factors to address. "Best practice"
      intervention is proposed as implementing and strengthening graduated driver
      licensing systems and complementary candidate programs and research, such as
      hazard perception training programs. A schematic cognitive-perceptual model to
      explain the crash sequence process is explored. There is optimism that meaningful
      impacts can be made, especially coupled with the advances in vehicle
      technologies, but caution is necessary in the absence of targeted "real world"
      evaluations and broader implementation and diffusion strategies.

PMID- 16788113
TI  - A conceptual framework for reducing risky teen driving behaviors among minority
      youth.
AB  - Teenage drivers, especially males, have higher rates of motor vehicle crashes and
      engage in riskier driving behavior than adults. Motor vehicle deaths
      disproportionately impact youth from poor and minority communities and in many
      communities there are higher rates of risky behaviors among minority youth. In
      this paper, the authors review the data on teens, risky driving behaviors, and
      morbidity and mortality. They identify areas in which known disparities exist,
      and examine strategies for changing teen driving behavior, identifying what has
      worked for improving the use of seat belts and for reducing other risky
      behaviors. A multifaceted, multilevel model based on ecological theory is
      proposed for understanding how teens make choices about driving behaviors, and to
      understand the array of factors that can influence these choices. The model is
      used to create recommendations for comprehensive intervention strategies that can
      be used in minority communities to reduce disparities in risk behaviors, injury,
      disability, and death.

PMID- 16788116
TI  - The cover. The Grands Boulevards.

PMID- 16788115
TI  - Influences on youthful driving behavior and their potential for guiding
      interventions to reduce crashes.
AB  - This paper presents an organized, comprehensive view of the factors known to
      influence young drivers' behavior and how those factors might inform
      interventions to reduce crashes. This effort was done from the perspective of a
      public health professional, with a background in health behavior and health
      education, interested in preventing injury and death among young people from
      motor vehicle crashes. The author's own studies, selected relevant literature,
      observation, and experience were considered and organized. A framework of six
      categories of influences on youthful driving behavior was developed, including
      the following elements: driving ability, developmental factors, personality
      factors, demographics, the perceived environment, and the driving environment. It
      is apparent that a complex set of many different factors influences young
      drivers' behavior. To reduce crashes, comprehensive, multilevel interventions are
      needed that target those factors in the framework that are amenable to change.

PMID- 16788117
TI  - A piece of my mind. At face value.

PMID- 16788119
TI  - Group backs emergency contraception.

PMID- 16788118
TI  - National plan for pandemic flu unveiled.

PMID- 16788120
TI  - CDC: immunize more children for influenza.

PMID- 16788121
TI  - Scientists plan New Orleans Mold Project.

PMID- 16788122
TI  - Statins and the risk of cancer.

PMID- 16788123
TI  - Statins and the risk of cancer.

PMID- 16788124
TI  - Statins and the risk of cancer.

PMID- 16788125
TI  - Cost-effectiveness analysis in the United States.

PMID- 16788126
TI  - Cost-effectiveness and resource allocation.

PMID- 16788127
TI  - Repair of inguinal hernia vs watchful waiting.

PMID- 16788128
TI  - Repair of inguinal hernia vs watchful waiting.

PMID- 16788129
TI  - Incomplete financial disclosure for study of funding and outcomes in major
      cardiovascular trials.

PMID- 16788130
TI  - Statin use and incident nuclear cataract.
AB  - CONTEXT: Statins are widely prescribed for their lipid-lowering effects but also
      have putative antioxidant properties. Oxidative stress is believed to play a role
      in the development of nuclear cataract, but little is known regarding the
      relationship of statin use and cataract incidence. OBJECTIVE: To evaluate the
      relationship of use of statins and incident cataract in adults in a midwestern
      community in the United States. DESIGN, SETTING, AND PARTICIPANTS: The Beaver Dam
      Eye Study, an observational, longitudinal, population-based study of age-related
      eye disease in Beaver Dam, Wis. There were 1299 persons who were seen at the
      third examination in 1998-2000, had gradable photographs in both eyes, and were
      deemed to be at risk of developing nuclear cataract within 5 years. MAIN OUTCOME
      MEASURE: Five-year incidence of cataract with respect to statin use. Cataracts
      were graded from photographs taken through the participant's dilated pupil.
      RESULTS: A total of 210 persons developed incident nuclear cataract in the
      interval from 1998-2000 to 2003-2005. Five-year incidence of nuclear cataract was
      12.2% in statin users compared with 17.2% in nonusers (odds ratio [OR], 0.55; 95%
      confidence interval [CI], 0.36-0.84), controlling for age. When only never
      smokers without diabetes were assessed, the age-, lipid level-, and sex-adjusted
      OR was 0.40 (95% CI, 0.18-0.90). Five-year incidence of cortical cataract was
      9.9% in statin users and 7.5% in nonusers (OR, 1.28; 95% CI, 0.79-2.08);
      posterior subcapsular cataract occurred in 3.0% of statin users and 3.4% of
      nonusers (OR, 0.82; 95% CI, 0.39-1.71). CONCLUSION: Statin use in a general
      population appears to be associated with lower risk of nuclear cataract, the most
      common type of age-related cataract.

PMID- 16788131
TI  - How conducting a clinical trial affects physicians' guideline adherence and drug
      preferences.
AB  - CONTEXT: General practitioners are frequently involved in clinical trials
      sponsored by pharmaceutical companies but the effects of participation on their
      prescribing patterns have not been evaluated. OBJECTIVE: To determine how
      conducting a company-sponsored clinical trial influenced physicians' adherence to
      international treatment recommendations and their prescribing of the
      pharmaceutical company's drugs. DESIGN, SETTING, AND PATIENTS: Observational
      cohort study in Funen County, Denmark, comparing 10 practices that were
      conducting a trial on asthma medicine with 165 control (non-trial-conducting)
      practices. The study population included 5439 patients treated with asthma drugs
      from the trial-conducting practices and 59,574 patients from the control
      practices. Practices conducted the trial between April 26, 2001, and October 7,
      2002. MAIN OUTCOME MEASURES: Adherence to guidelines measured as use of inhaled
      corticosteroids among asthma patients. Prevalence of use of the company's drugs
      and the trial sponsor's share of the total volume of asthma drugs prescribed.
      RESULTS: The baseline proportion of asthma patients using inhaled corticosteroids
      was 68.5% in trial-conducting and 69.1% in control practices. Conducting the
      trial did not influence guideline adherence (odds ratio [OR] after 2 years, 1.00;
      95% confidence interval [CI], 0.84-1.19). In trial-conducting practices, the
      sponsoring company's share of the total prescribed volume of asthma drugs
      increased compared with control practices (6.7%; 95% CI, 3.0%-11.7%). This could
      be attributed to a significantly higher preference for the company's inhaled
      corticosteroids (OR, 1.26; 95% CI, 1.04-1.54) and trends toward increased
      prescribing of the company's other asthma drugs. CONCLUSION: Conducting a trial
      sponsored by a pharmaceutical company had no significant impact on physicians'
      adherence to international treatment recommendations but increased their use of
      the trial sponsor's drugs.

PMID- 16788132
TI  - Prophylaxis strategies for contrast-induced nephropathy.
AB  - CONTEXT: Contrast-induced nephropathy is associated with significant economic and
      clinical consequences, including prolonged hospitalization, the requirement for
      dialysis, and an increased risk of death. OBJECTIVES: To summarize the current
      state of evidence for prophylaxis of contrast-induced nephropathy, provide
      evidence-based recommendations regarding management of high-risk patients
      undergoing angiographic procedures, and identify new avenues for research. DATA
      SOURCES: Systematic searches of peer-reviewed publications were performed in
      MEDLINE, EMBASE, and the Cochrane database from 1966 to January 2006. Search
      terms included radio contrast nephropathy, contrast media, acetylcysteine,
      theophylline, sodium bicarbonate, HMG Co-A reductase inhibitors, ascorbic acid,
      kidney diseases, renal insufficiency, kidney failure, nephropathy, fenoldopam,
      diuretics, and saline or half saline. STUDY SELECTION: Observational studies of
      risk factors and randomized controlled trials of prophylaxis strategies for
      contrast-induced nephropathy that specified a definition of contrast-induced
      nephropathy or postprocedure creatinine level as an outcome measure. Evidence
      Synthesis Important patient-related risk factors for contrast-induced nephropathy
      include chronic kidney disease, diabetes mellitus, heart failure, older age,
      anemia, and left ventricular systolic dysfunction. Non-patient-related risk
      factors include high-osmolar contrast, ionic contrast, contrast viscosity, and
      contrast volume. Practice guidelines recommend obtaining preprocedural serum
      creatinine levels among patients with renal disease, diabetes, proteinuria,
      hypertension, gout, or congestive heart failure. Available evidence, largely
      based on small- to medium-sized trials, supports the use of hydration,
      bicarbonate, and low volumes of iso- or low-osmolar contrast in patients at risk.
      N-acetylcysteine or ascorbic acid may be of value in very high-risk patients.
      CONCLUSIONS: While several risk factors for contrast-induced nephropathy have
      been identified, the development of an effective prophylaxis strategy for
      contrast-induced nephropathy has been limited by our poor understanding of the
      pathophysiology and the clinical significance of this condition. Future research
      should focus on correctly identifying higher-risk patients and testing therapies
      in the setting of large well-powered clinical trials.

PMID- 16788133
TI  - Expected and unanticipated consequences of the quality and information technology
      revolutions.

PMID- 16788134
TI  - Clinical trial investigators and their prescribing patterns: another dimension to
      the relationship between physician investigators and the pharmaceutical industry.

PMID- 16788135
TI  - JAMA patient page. Randomized controlled trials.

PMID- 16788136
TI  - Endothelin-A and -B receptors, superoxide, and Ca2+ signaling in afferent
      arterioles.
AB  - It is unknown if endothelin-A and -B receptors (ET(A)R and ET(B)R) activate the
      production of superoxide via NAD(P)H oxidase and subsequently stimulate the
      formation of cyclic adenine diphosphate ribose (cADPR) in afferent arterioles.
      Vessels were isolated from rat kidney and loaded with fura 2. Endothelin-1 (ET-1)
      rapidly increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) by 303 nM. The
      superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and
      nicotinamide, an inhibitor of ADPR cyclase, diminished the response by
      approximately 60%. The ET(B)R agonist sarafotoxin 6c (S6c) increased peak
      [Ca(2+)](i) by 117 nM. Subsequent addition of ET-1 in the continued presence of
      S6c caused an additional [Ca(2+)](i) peak of 225 nM. Neither nicotinamide or 8
      bromo- (8-Br) cADPR nor apocynin decreased the [Ca(2+)](i) response to S6c, but
      inhibited the subsequent [Ca(2+)](i) response to ET-1. The ET(B)R blockers BQ-788
      and A-192621 prevented the S6c [Ca(2+)](i) peak and reduced the ET-1 response by
      more than one-half, suggesting an ET(B)R/ET(A)R interaction. In contrast, the
      ET(A)R blocker BQ-123 had no effect on the S6c [Ca(2+)](i) peak and obliterated
      the subsequent ET-1 response. ET-1 immediately stimulated superoxide formation
      (measured with TEMPO-9-AC, 68 arbitrary units) that was inhibited 95% by apocynin
      or diphenyl iodonium. S6c or IRL-1620 increased superoxide by 8% of that caused
      by subsequent ET-1 addition. We conclude that ET(A)R activation of afferent
      arterioles increases the formation of superoxide that accounts for approximately
      60% of subsequent Ca(2+) signaling. ET(B)R activation appears to result in only
      minor increases in superoxide production. Nicotinamide and 8-Br-cADPR results
      suggest that ET-1 (and primarily ET(A)R) causes the activation of vascular smooth
      muscle cell-ADPR cyclase.

PMID- 16788137
TI  - Regulation of the expression of the Na/Cl cotransporter by WNK4 and WNK1:
      evidence that accelerated dynamin-dependent endocytosis is not involved.
AB  - The novel serine/threonine kinases (with no lysine kinases or WNKs), WNK1 and
      WNK4, are encoded by the disease genes for Gordon syndrome (PRKWNK1 and PRKWNK4),
      a rare monogenic syndrome of hypertension and hyperkalemia. These proteins alter
      the expression of the thiazide-sensitive Na/Cl cotransporter (NCCT) in Xenopus
      laevis oocytes, although the details are controversial. We describe here our own
      experience and confirm that kinase-dead WNK4 (318D>A) is unable to affect Na+
      fluxes through the thiazide-sensitive Na/Cl transporter (NCCT) or its membrane
      expression as an ECFP-NCCT fusion protein. However, the kinase domain is not
      sufficient for a functional WNK4 since deletion of the acidic motif (a motif
      unique to WNK family members) completely abolishes functional activity. Indeed,
      the NH2 terminal of WNK4 (1-620) containing the kinase domain and acidic motif
      retains full activity, but does not interact directly with NCCT in pull-down
      assays. Coexpression of WNK1 antagonizes the action of WNK4, and kinase-dead WNK1
      (368D>A) or WNK1 carrying a WNK4 disease mutation (565Q>E) behaves in the same
      way as wild-type WNK1. This suggests kinase activity and charge conservation
      within the acidic motif are not essential for the WNK1-WNK4 interaction. We also
      report that WNK4 probably reduces surface expression largely through an effect on
      forward trafficking. Hence, the effect of WNK4 on NCCT expression is mimicked by
      dynamin, but the dominant-negative K44A dynamin mutant does not block the action
      of WNK4 itself. These results further highlight important differences in the
      mechanism by which WNK kinases affect expression of NCCT vs. other membrane
      proteins such as ROMK.

PMID- 16788138
TI  - Expression and distribution of HuR during ATP depletion and recovery in proximal
      tubule cells.
AB  - Human antigen R (HuR) is a nucleocytoplasmic shuttling protein that binds to and
      stabilizes mRNAs containing adenine- and uridine-rich elements. Under normal
      growth conditions, the bulk of HuR is maintained in the nucleus, but under
      conditions of cell stress, HuR may become more prevalent in the cytosol, where it
      can stabilize mRNA and regulate gene expression. We have studied the behavior of
      HuR in LLC-PK1 proximal tubule cells subjected to ATP depletion and recovery. ATP
      depletion resulted in detectable net movement of HuR out of the nucleus, followed
      by net movement of HuR back into the nucleus on reversion to normal growth
      medium. In addition, HuR protein levels increased during energy depletion. This
      increase was inhibited by cycloheximide and was independent of HuR mRNA levels,
      since no change was noted in the quantity of HuR transcript. In contrast,
      recovery in normal growth medium resulted in increased HuR mRNA, while protein
      levels decreased to baseline. This suggested a mechanism by which previously
      injured cells maintained normal levels of HuR but were primed to rapidly
      translate increased amounts of protein on subsequent insults. Indeed, a second
      round of ATP depletion resulted in heightened HuR protein translation at a rate
      more rapid than during the first insult. Additionally, the second insult produced
      increased HuR levels in the cytoplasm while still maintaining high amounts in the
      nucleus, indicating that nuclear export may not be required on subsequent
      insults. These results suggest a role for HuR in protecting kidney epithelia from
      injury during ischemic stress.

PMID- 16788139
TI  - Renal vascular endothelial growth factor in neonatal obstructive nephropathy. II.
      Exogenous VEGF.
AB  - Chronic unilateral ureteral obstruction (UUO) in the neonatal rat causes delayed
      renal maturation, tubular apoptosis, and interstitial inflammation. Vascular
      endothelial growth factor (VEGF) acts as a survival factor for tubular cells and
      reduces renal injury in several models of renal disease. To determine whether
      exogenous VEGF attenuates renal injury from UUO, rats were subjected within the
      first 48 h of life to sham operation, partial UUO, or complete UUO. Saline
      vehicle or VEGF(121) (50 mg/kg) was injected twice daily for 7 days, after which
      kidneys were harvested for histological study. The density of peritubular
      capillaries was measured with platelet-endothelial cell adhesion molecule-1
      immunostaining, proliferating nuclei were detected by proliferating-cell nuclear
      antigen staining, apoptosis by the transferase-mediated dUTP nick end-labeling
      technique, macrophages by ED-1 immunostaining, and collagen by Sirius red
      staining. Glomerular number and maturation index were also determined in each
      group. Following chronic complete UUO in the neonatal rat, peritubular capillary
      density was significantly decreased. Cortical capillary density was further
      reduced by exogenous VEGF in the partially obstructed kidney. While UUO also
      decreased glomerular number and delayed glomerular maturation, exogenous VEGF
      exerted no additional effects. Cellular proliferation and tubular apoptosis
      increased in proportion to the severity of obstruction, but exogenous VEGF had no
      additional effects on proliferation, tubular apoptosis, or macrophage
      infiltration. However, VEGF reduced interstitial apoptosis in the kidney with
      partial UUO. We conclude that VEGF does not have salutary effects on the renal
      lesions caused by chronic UUO in the neonatal rat and may actually worsen
      obstructive nephropathy by aggravating the interstitial lesions.

PMID- 16788140
TI  - Renal vascular endothelial growth factor in neonatal obstructive nephropathy. I.
      Endogenous VEGF.
AB  - Obstructive nephropathy constitutes a major cause of renal impairment in
      children. Chronic unilateral ureteral obstruction (UUO) impairs maturation of the
      developing kidney and leads to tubular apoptosis and interstitial inflammation.
      Vascular endothelial growth factor (VEGF) is involved in recovery from various
      forms of renal injury. We questioned whether the renal expression of endogenous
      VEGF and its receptor (VEGFR2/Flk-1) is modified by UUO in early development.
      Neonatal rats were subjected to partial or complete UUO or sham operation. The
      distribution of immunoreactive VEGF in each kidney was examined after 7, 14, or
      28 days. Adult rats were also subjected to sham operation or complete UUO.
      Tubular VEGF increased between 14 and 28 days in sham-operated rats and in some
      partially obstructed neonatal rats but decreased with complete UUO. Parallel
      changes were found by Western blotting, but not by RT-PCR. Immunoreactive VEGF
      colocalized with mitochondria in proximal and distal tubules and also appeared in
      type A intercalated cells, glomerular vascular endothelium, and podocytes. While
      neonatal microvascular renal VEGFR2 receptor staining was strongly positive
      regardless of UUO, staining was weak in sham-operated adults but increased
      following UUO. Parallel changes in VEGFR2 expression were verified by RT-PCR and
      Western blotting. We conclude that endogenous renal VEGF is developmentally
      regulated in the neonatal rat and is differentially regulated by partial and
      complete UUO. Following UUO in the adult, the VEGF receptor is upregulated.
      Endogenous VEGF may serve an adaptive role in responding to tubular injury caused
      by UUO and may modulate adaptation by the contralateral kidney.

PMID- 16788141
TI  - Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to
      angiotensin II or norepinephrine-induced acute hypertension.
AB  - The kidney responds to high levels of ANG II, as may occur during malignant
      hypertension, by increasing sodium and water excretion. To study whether kidney
      medullary transporters contribute to this response, rats were made hypertensive
      using ANG II. Within 3 days of being given ANG II, systolic blood pressure (BP)
      was increased (200 mmHg), vs control (130 mmHg), and remained high through day
      14. Kidney inner medullary (IM) tip and base and outer medulla were analyzed for
      transporter protein abundance. There were significant decreases in UT-A1 urea
      transporter, aquaporin-2 (AQP2) water channel, and NKCC2/BSC1 Na(+)-K(+)-2Cl(-)
      cotransporter. To determine whether the decreases were a response to
      hypertension, ANG II, or an ANG II-induced increase in aldosterone, rats were
      given 1) norepinephrine (to increase BP) and 2) ANG II plus spironolactone (to
      block the mineralocorticoid receptor). Norepinephrine (7 days) increased BP,
      urine volume, sodium excretion, and decreased urine osmolality and UT-A1, AQP2,
      and NKCC2/BSC1 abundances, similar to ANG II. ANG II alone or with spironolactone
      yielded similar increases in BP, urine volume, and urine osmolality, and
      decreases in UT-A1 and AQP2 proteins in the IM tip. Plasma vasopressin was
      unaffected by treatment. Water diuresis did not change UT-A1 but decreased AQP2
      and NKCC2/BSC1 abundances. We conclude that decreases in UT-A1, AQP2, and
      NKCC2/BSC1 proteins may contribute to the diuresis and natriuresis that occur
      following ANG II or norepinephrine-induced acute hypertension and do not appear
      to involve ANG II stimulation of aldosterone or thirst.

PMID- 16788143
TI  - Polarized biosynthetic traffic in renal epithelial cells: sorting, sorting,
      everywhere.
AB  - The maintenance of apical and basolateral membrane domains with distinct protein
      and lipid compositions is necessary for the proper function of polarized
      epithelial cells. Delivery of cargo to the basolateral surface is thought to be
      mediated by the interaction of cytoplasmically disposed sorting signals with
      sorting receptors, whereas apically destined cargoes are sorted via mechanisms
      dependent on cytoplasmic, glycan-mediated, or lipid-interacting sorting signals.
      Apical and basolateral cargo are delivered to the surface in discrete tubular and
      vesicular carriers that bud from the trans-Golgi network (TGN). While it has long
      been thought that the TGN is the primary compartment in which apical and
      basolateral cargoes are segregated, recent studies suggest that sorting may begin
      earlier along the biosynthetic pathway. Moreover, rather than being delivered
      directly from the TGN to the cell surface, at least a subset of biosynthetic
      cargo appears to transit recycling endosomes en route to the plasma membrane. The
      implications and limitations of these challenges to the conventional model for
      how proteins are sorted and trafficked along the biosynthetic pathway are
      discussed.

PMID- 16788142
TI  - Oxidative stress and glomerular filtration barrier injury: role of the renin
      angiotensin system in the Ren2 transgenic rat.
AB  - TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, manifest
      hypertension, and exhibit increased tissue ANG II levels and oxidative stress.
      Evidence indicates that elevated tissue ANG II contributes to oxidative stress,
      increases in glomerular macromolecular permeability, and consequent albuminuria.
      Furthermore, angiotensin type 1 receptor (AT1R) blockers reduce albuminuria and
      slow progression of renal disease. However, it is not known whether improvements
      in glomerular filtration barrier integrity and albuminuria during treatment are
      related to reductions in oxidative stress and/or kidney renin-angiotensin system
      (RAS) activity. To investigate the renal protective effects of AT1R blockade, we
      treated young (6-7 wk old) male Ren2 rats with valsartan (Ren2-V; 30 mg/kg) for 3
      wk and measured urine albumin, kidney malondialdehyde (MDA), RAS component mRNAs,
      and NADPH oxidase subunits (gp91(phox) and Rac1) compared with age-matched
      untreated Ren2 and Sprague-Dawley (S-D) rats. Basement membrane thickness, slit
      pore diameter and number, and foot process base width were measured by
      transmission electron microscopy (TEM). Results indicate that AT1R blockade
      lowered systolic blood pressure (30%), albuminuria (91%), and kidney MDA (80%) in
      Ren2-V compared with untreated Ren2 rats. Increased slit pore number and diameter
      and reductions in basement membrane thickness and podocyte foot process base
      width were strongly associated with albuminuria and significantly improved
      following AT1R blockade. AT1R blockade was also associated with increased
      angiotensin-converting enzyme-2 and neprilysin expression, demonstrating a
      beneficial shift in balance of renal RAS. Thus reductions in blood pressure,
      albuminuria, and tissue oxidative stress with AT1R blockade were associated with
      improved indexes of glomerular filtration barrier integrity and renal RAS in Ren2
      rats.

PMID- 16788144
TI  - Mre11-Rad50-Nbs1 complex is activated by hypertonicity.
AB  - When exposed to hypertonic conditions, cells accumulate double-strand DNA breaks
      (DSBs) like they are exposed to ionizing radiation. It has been proposed that
      inactivation of the Mre11-Rad50-Nbs1 (MRN) complex due to nuclear exit is
      responsible for the accumulation of DSBs as cells fail to repair DSBs produced
      during normal cellular activity. In this study, we examined the MRN complex in
      cells switched to hypertonicity. Surprisingly, we found that the MRN complex
      stayed in the nucleus and remained intact in response to hypertonicity. In fact,
      the MRN complex was dramatically activated after 4 h of switch to hypertonicity
      in a dose-dependent manner as shown by formation of foci. Activation of ATM and
      the MRN complex by hypertonicity and bleomycin was additive as was activation of
      their downstream targets including gammaH2AX and Chk2 indicating that the
      cellular response to DSB was intact in hypertonic conditions. Activation of Chk2
      in response to hypertonicity was not observed in mutant cells with functionally
      impaired MRN complex confirming that they are in the same pathway. After 20 h of
      a switch to hypertonicity, MRN foci and gammaH2AX returned to a control level,
      suggesting that cells adapted to hypertonicity by repairing DNA. We conclude that
      cells respond normally to DSB and repair the DNA damages induced by
      hypertonicity.

PMID- 16788145
TI  - Renal cortical regulation of COX-1 and functionally related products in early
      renovascular hypertension (rat).
AB  - Renal volume regulation is modulated by the action of cyclooxygenases (COX) and
      the resulting generation of prostanoids. Epithelial expression of COX isoforms in
      the cortex directs COX-1 to the distal convolutions and cortical collecting duct,
      and COX-2 to the thick ascending limb. Partly colocalized are prostaglandin E
      synthase (PGES), the downstream enzyme for renal prostaglandin E(2) (PGE(2))
      generation, and the EP receptors type 1 and 3. COX-1 and related components were
      studied in two kidney-one clip (2K1C) Goldblatt hypertensive rats with combined
      chronic ANG II or bradykinin B(2) receptor blockade using candesartan (cand) or
      the B(2) antagonist Hoechst 140 (Hoe). Rats (untreated sham, 2K1C, sham + cand,
      2K1C + cand, sham + Hoe, 2K1C + Hoe) were treated to map expression of parameters
      controlling PGE(2) synthesis. In 2K1C, cortical COX isoforms did not change
      uniformly. COX-2 changed in parallel with NO synthase 1 (NOS1) expression with a
      raise in the clipped, but a decrease in the nonclipped side. By contrast, COX-1
      and PGES were uniformly downregulated in both kidneys, along with reduced urinary
      PGE(2) levels, and showed no clear relations with the NO status. ANG II receptor
      blockade confirmed negative regulation of COX-2 by ANG II but blunted the
      decrease in COX-1 selectively in nonclipped kidneys. B(2) receptor blockade
      reduced COX-2 induction in 2K1C but had no clear effect on COX-1. We suggest that
      in 2K1C, COX-1 and PGES expression may fail to oppose the effects of renovascular
      hypertension through reduced prostaglandin signaling in late distal tubule and
      cortical collecting duct.

PMID- 16788147
TI  - Transporter regulator RS1 (RSC1A1) coats the trans-Golgi network and migrates
      into the nucleus.
AB  - The product of gene RSC1A1, named RS1, is involved in transcriptional and
      posttranscriptional regulation of sodium-d-glucose cotransporter SGLT1, and
      removal of RS1 in mice led to an increase of SGLT1 expression in small intestine
      and to obesity (Osswald C, Baumgarten K, Stumpel F, Gorboulev V, Akimjanova M,
      Knobeloch K-P, Horak I, Kluge R, Joost H-G, and Koepsell H. Mol Cell Biol 25: 78
      87, 2005). Previous data showed that RS1 inhibits transcription of SGLT1 in LLC
      PK1 cells derived from porcine kidney. A decrease of the intracellular amount of
      RS1 protein was observed during cell confluence, which was paralleled by
      transcriptional upregulation of SGLT1. In the present study, the subcellular
      distributions of endogenously expressed RS1 and SGLT1 were compared in LLC-PK1
      cells and human embryonic kidney (HEK)-293 cells using immunofluorescence
      microscopy. RS1 was located at the plasma membrane, at the entire trans-Golgi
      network (TGN), and within the nucleus. Treatment of LLC-PK1 cells with brefeldin
      A induced rapid release of RS1 from the TGN, and confluence of LLC-PK1 cells was
      accompanied by reduction of nuclear location of RS1; 84-90% of subconfluent cells
      and 5-34% of confluent cells contained RS1 in the nuclei. This suggests that
      confluence-dependent transcriptional inhibition by RS1 is partially regulated by
      nuclear migration. Furthermore, we assigned SGLT1 to microtubule-associated
      tubulovesicular structures and dynamin-containing parts of the TGN. The data
      indicate that RS1 inhibits the dynamin-dependent release of SGLT1-containing
      vesicles from the TGN.

PMID- 16788146
TI  - RS1 (RSC1A1) regulates the exocytotic pathway of Na+-D-glucose cotransporter
      SGLT1.
AB  - The product of gene RSC1A1, named RS1, participates in transcriptional and
      posttranscriptional regulation of the sodium-d-glucose cotransporter SGLT1. Using
      coexpression in oocytes of Xenopus laevis, posttranscriptional inhibition of
      human SGLT1 (hSGLT1) and some other transporters by human RS1 (hRS1) was
      demonstrated previously. In the present study, histidine-tagged hRS1 was
      expressed in oocytes or Sf9 cells and purified using nickel(II)-charged
      nitrilotriacetic acid-agarose. hRS1 protein was injected into oocytes expressing
      hSGLT1 or the human organic cation transporter hOCT2, and the effect on hSGLT1
      mediated uptake of methyl-alpha-D-[14C]glucopyranoside ([14C]AMG) or hOCT2
      mediated uptake of [14C]tetraethylammonium ([14C]TEA) was measured. Within 30 min
      after the injection of hRS1 protein, hSGLT1-expressed AMG uptake or hOCT2
      expressed TEA uptake was inhibited by approximately 50%. Inhibition of AMG uptake
      was decreased when a dominant negative mutant of dynamin I was coexpressed and
      increased after stimulation of PKC. Inhibition remained unaltered when
      endocytosis was inhibited by chlorpromazine, imipramine, or filipin but was
      prevented when exocytosis was inhibited by botulinum toxin B or when the release
      of vesicles from the TGN and endosomes was inhibited by brefeldin A. Inhibition
      of hSGLT1-mediated AMG uptake and hOCT2-mediated TEA uptake by hRS1 protein were
      decreased at an enhanced intracellular AMG concentration. The data suggest that
      hRS1 protein exhibits glucose-dependent, short-term inhibition of hSGLT1 and
      hOCT2 by inhibiting the release of vesicles from the trans-Golgi network.

PMID- 16788148
TI  - A new tumor suppressor gene: invasion, metastasis, and angiogenesis as potential
      key targets.

PMID- 16788149
TI  - Timing of androgen deprivation therapy: some questions answered, others not.

PMID- 16788150
TI  - Slow start to phase 0 as researchers debate value.

PMID- 16788151
TI  - Stat bite: Probability of developing invasive cancers over selected ages, 2000
      2002.

PMID- 16788152
TI  - Circadian rhythms play role in cancer research.

PMID- 16788153
TI  - PTEN takes center stage in cancer stem cell research, works as tumor suppressor.

PMID- 16788154
TI  - Researchers may use cancer cell lines to identify target populations prior to
      clinical trials.

PMID- 16788155
TI  - Keratinocyte growth factor expression and activity in cancer: implications for
      use in patients with solid tumors.
AB  - Keratinocyte growth factor (KGF) is a locally acting epithelial mitogen that is
      produced by cells of mesenchymal origin and has an important role in protecting
      and repairing epithelial tissues. Use of recombinant human KGF (palifermin) in
      patients with hematologic malignancies reduces the incidence and duration of
      severe oral mucositis experienced after intensive chemoradiotherapy. These
      results suggest that KGF may be useful in the treatment of patients with other
      kinds of tumors, including those of epithelial origin. However, its application
      in this context raises issues that were not pertinent to its use in hematologic
      cancer because epithelial tumor cells, unlike blood cells, often express the KGF
      receptor (FGFR2b). Thus, it is important to examine whether KGF could promote the
      growth of epithelial tumors or protect such tumor cells from the effects of
      chemotherapy agents. Analyses of KGF and FGFR2b expression in tumor specimens and
      of KGF activity on transformed cells in vitro and in vivo do not indicate a
      definitive role for KGF in tumorigenesis. On the contrary, restoring FGFR2b
      expression to certain malignant cells can induce cell differentiation or
      apoptosis. However, other observations suggest that, in specific situations, KGF
      may contribute to epithelial tumorigenesis. Thus, further studies are warranted
      to examine the nature and extent of KGF involvement in these settings. In
      addition, clinical trials in patients with solid tumors are underway to assess
      the potential benefits of using KGF to protect normal tissue from the adverse
      effects of chemoradiotherapy and its possible impact on clinical outcome.

PMID- 16788156
TI  - A new tumor suppressor DnaJ-like heat shock protein, HLJ1, and survival of
      patients with non-small-cell lung carcinoma.
AB  - BACKGROUND: We previously identified DnaJ-like heat shock protein (HLJ1) as a
      gene associated with tumor invasion. Here, we investigated the clinical
      significance of HLJ1 expression in non-small-cell lung cancer (NSCLC) patients
      and its role in cancer progression. METHODS: We induced HLJ1 overexpression or
      knockdown in human lung adenocarcinoma CL1-5 cells and analyzed cell
      proliferation, anchorage-independent growth, in vivo tumorigenesis, cell
      motility, invasion, and cell cycle progression. Expression of genes that act
      downstream of HLJ1 was examined by DNA microarray analysis, pathway analysis, and
      western blotting. We measured HLJ1 expression in tumors and adjacent normal
      tissues of 71 NSCLC patients by quantitative reverse transcription-polymerase
      chain reaction. Associations between HLJ1 expression and disease-free and overall
      survival were determined using the log-rank test and multivariable Cox
      proportional hazards regression analysis. Validation was performed in an
      independent cohort of 56 NSCLC patients. Loss of heterozygosity (LOH) mapping of
      the HLJ1 locus was analyzed in 48 paired microdissected NSCLC tumors. All
      statistical tests were two-sided. RESULTS: HLJ1 expression inhibited lung cancer
      cell proliferation, anchorage-independent growth, tumorigenesis, cell motility,
      and invasion, and slowed cell cycle progression through a novel STAT1/P21(WAF1)
      pathway that is independent of P53 and interferon. HLJ1 expression was lower in
      tumors than in adjacent normal tissue in 55 of 71 patients studied. NSCLC
      patients with high HLJI expressing tumors had reduced cancer recurrence (hazard
      ratio [HR] = 0.47; 95% confidence interval [CI] = 0.23 to 0.93; P = .03) and
      longer overall survival (HR = 0.38; 95% CI = 0.16 to 0.89; P = .03) than those
      with low-expressing tumors. Validation in the independent patient cohort
      confirmed the association between HLJ1 expression and patient outcome. LOH
      mapping revealed high frequencies (66.7% and 70.8%) of allelic loss and
      microsatellite instability (87.5% and 95.2%) of the HLJ1 locus at chromosome
      1p31.1. CONCLUSIONS: HLJ1 is a novel tumor suppressor in NSCLC, and high HLJ1
      expression is associated with reduced cancer recurrence and prolonged survival of
      NSCLC patients.

PMID- 16788157
TI  - Determinants of androgen deprivation therapy use for prostate cancer: role of the
      urologist.
AB  - BACKGROUND: The use of androgen deprivation therapy for prostate cancer has been
      increasing, even in settings for which there is weak or no evidence of efficacy.
      This pattern suggests that factors other than the typical patient and tumor
      characteristics may be driving its use. We assessed the importance of the
      physician as a determinant of the use of androgen deprivation therapy in prostate
      cancer in a population-based, retrospective cohort study using the Surveillance,
      Epidemiology and End-Results-Medicare linked database. METHODS: Participants
      included 61 717 men with incident prostate cancer diagnosed from January 1, 1992,
      through December 31, 1999, and 1802 urologists providing care to them within 1
      year of cancer diagnosis. Multilevel analyses were used to estimate and partition
      the variance in use of androgen deprivation therapy within 6 months of diagnosis
      between patient or tumor characteristics and urologist to examine the relative
      contribution of each component to androgen deprivation therapy. RESULTS: The
      percentage of the total variance in the use of androgen deprivation therapy
      attributable to the urologist was consistently higher than that attributable to
      tumor or patient characteristics. This pattern was most pronounced for patients
      diagnosed from January 1, 1997, through December 31, 1999, in which 22.56% of the
      total variance in use of androgen deprivation therapy was attributable to the
      urologist, 9.71% to tumor characteristics (stage or grade), and 4.29% to patient
      characteristics (age, ethnicity, socio-economic status, comorbidity, geographic
      region, or year of diagnosis). CONCLUSIONS: Which urologist a patient sees may be
      more important in determining whether they will receive androgen deprivation
      therapy than tumor or patient characteristics.

PMID- 16788159
TI  - Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein
      degradation.
AB  - BACKGROUND: Sp1, Sp3, and Sp4 are transcription factors that regulate cell
      proliferation and vascular endothelial growth factor (VEGF) expression and are
      overexpressed in many cancer cell lines. For some cancers, Sp1 overexpression is
      associated with poor survival. Cyclooxygenase inhibitors decrease Sp1 expression
      in cancer cells, and therefore different structural classes of nonsteroidal anti
      inflammatory drugs (NSAIDs) were screened for their ability to decrease levels of
      Sp1, Sp3, and Sp4 and to decrease pancreatic tumor growth and metastasis in an in
      vivo model. METHODS: Levels of Sp1, Sp3, Sp4, and VEGF proteins in pancreatic
      cancer cell lines were assessed by immunoblot analysis. mRNA was assessed by
      reverse transcription-polymerase chain reaction. Panc-1 pancreatic cancer cells
      transfected with VEGF promoter constructs were used to assess VEGF promoter
      activation. Pancreatic tumor weight and size and liver metastasis were assessed
      in an orthotopic mouse model of pancreatic cancer (groups of 10 mice). Protein
      expression in tumors was assessed immunohistochemically. RESULTS: Tolfenamic acid
      and structurally related biaryl derivatives induced degradation of Sp1, Sp3, and
      Sp4 in pancreatic cancer cells. Tolfenamic acid also inhibited VEGF mRNA and
      protein expression in pancreatic cancer cells; this inhibition was associated
      with the decreased Sp-dependent activation of the VEGF promoter. In the mouse
      model for pancreatic cancer, treatment with tolfenamic acid (50 mg/kg of body
      weight), compared with control treatment, statistically significantly decreased
      tumor growth and weight (P = .005), liver metastasis (P = .027), and levels of
      Sp3 and VEGF (P = .009) and Sp1 and Sp4 (P = .006) proteins in tumors. For
      example, tumors from mice treated with tolfenamic acid (50 mg/kg) had
      statistically significantly lower VEGF levels (45%, 95% confidence interval = 39%
      to 51%; P = .009) than tumors from control mice. CONCLUSIONS: Tolfenamic acid is
      a new antipancreatic cancer NSAID that activates degradation of transcription
      factors Sp1, Sp3, and Sp4; reduces VEGF expression; and decreases tumor growth
      and metastasis.

PMID- 16788158
TI  - Effect of silibinin on the growth and progression of primary lung tumors in mice.
AB  - BACKGROUND: Silibinin, a flavanone from milk thistle, inhibits the growth of
      tumors in several rodent models. We examined the effects of dietary silibinin on
      the growth, progression, and angiogenesis of urethane-induced lung tumors in
      mice. METHODS: A/J mice (15 per group) were injected with urethane (1 mg/g body
      weight) or saline alone and fed normal diets for 2 weeks, after which they were
      fed diets containing different doses of silibinin (0%-1% [wt/wt] silibinin) for
      18 or 27 weeks. Immunohistochemistry and Western blot analysis were used to
      examine angiogenesis and enzymatic markers of inflammation, proliferation, and
      apoptosis. All statistical tests were two-sided. RESULTS: Urethane-injected mice
      exposed to silibinin had statistically significantly lower lung tumor
      multiplicities than urethane-injected mice fed the control diet lacking silibinin
      (i.e., control mice). Mice that received urethane and 1% (wt/wt) dietary
      silibinin for 18 weeks had 93% fewer large (i.e., 1.5-2.5-mm-diameter) lung
      tumors than control mice (mean number of tumors/mouse: 27 in the urethane group
      versus 2 in the urethane + 1% silibinin group, difference = 25 tumors/mouse, 95%
      confidence interval [CI] = 13 to 37 tumors/mouse, P = .005). Lung tumors of
      silibinin-fed mice had 41%-74% fewer cells positive for the cell proliferation
      markers proliferating cell nuclear antigen and cyclin D1 than lung tumors of
      control mice. Tumor microvessel density was reduced by up to 89% with silibinin
      treatment (e.g., 56 microvessels/400x field in tumors from control mice versus 6
      microvessels/400x field in tumors from urethane + 1% silibinin-treated mice
      [difference = 50 microvessels/400x field, 95% CI = 46 to 54 microvessels/400x
      field; P<.001]). Silibinin decreased lung tumor expression of vascular
      endothelial growth factor (VEGF) and of inducible nitric oxide synthase and
      cyclooxygenase-2, two enzymes that promote lung tumor growth and progression by
      inducing VEGF expression. CONCLUSIONS: Silibinin inhibits lung tumor angiogenesis
      in an animal model and merits investigation as a chemopreventive agent for
      suppressing lung cancer progression.

PMID- 16788160
TI  - Cadmium exposure and breast cancer risk.
AB  - Cadmium, a highly persistent heavy metal, has been categorized as a probable
      human carcinogen by the U.S. Environmental Protection Agency. Primary exposure
      sources include food and tobacco smoke. We carried out a population-based case
      control study of 246 women, aged 20-69 years, with breast cancer and 254 age
      matched control subjects. We measured cadmium levels in urine samples by
      inductively coupled plasma mass spectrometry and conducted interviews by
      telephone to obtain information on known breast cancer risk factors. Odds ratios
      (ORs) and 95% confidence intervals (CIs) for breast cancer by creatinine-adjusted
      cadmium levels were calculated by multivariable analysis. Statistical tests were
      two-sided. Women in the highest quartile of creatinine-adjusted cadmium level (>
      or = 0.58 microg/g) had twice the breast cancer risk of those in the lowest
      quartile (<0.26 microg/g; OR = 2.29, 95% CI = 1.3 to 4.2) after adjustment for
      established risk factors, and there was a statistically significant increase in
      risk with increasing cadmium level (P(trend) = .01). Based on this study, the
      absolute risk difference is 45 (95% CI = 0 to 77) per 100,000 given an overall
      breast cancer rate of 124 per 100,000. Whether increased cadmium is a causal
      factor for breast cancer or reflects the effects of treatment or disease remains
      to be determined.

PMID- 16788161
TI  - Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the
      incidence of intra- and extrahepatic cholangiocarcinoma in the United States.
AB  - Cholangiocarcinomas are topographically categorized as intrahepatic or
      extrahepatic by the International Classification of Diseases for Oncology (ICD
      O). Although hilar cholangiocarcinomas (Klatskin tumors) are extrahepatic
      cholangiocarcinomas, the second edition of the ICD-O (ICD-O-2) assigned them a
      histology code 8162/3, Klatskin, which was cross-referenced to intrahepatic
      cholangiocarcinoma. Recent studies in the United States that included this code
      (8162/3, Klatskin) with intrahepatic cholangiocarcinoma reported an increasing
      incidence of intrahepatic cholangiocarcinoma and a decreasing incidence of
      extrahepatic cholangiocarcinoma. To investigate the impact of this
      misclassification on site-specific cholangiocarcinoma incidence rates, we
      calculated annual percent changes (APCs) with data from the Surveillance,
      Epidemiology, and End Results (SEER) program using a Poisson regression model
      that was age-adjusted to the year 2000 U.S. population. All statistical tests
      were two-sided. During 1992-2000, when SEER used ICD-O-2, 1710 intrahepatic
      cholangiocarcinomas, 1371 extrahepatic cholangiocarcinomas, and 269 hilar
      cholangiocarcinomas identified by code 8162/3, Klatskin were diagnosed. Ninety
      one percent (246 of 269) of the hilar cholangiocarcinomas were incorrectly coded
      as intrahepatic cholangiocarcinomas, resulting in an overestimation of
      intrahepatic cholangiocarcinoma incidence by 13% and underestimation of
      extrahepatic cholangiocarcinomas incidence by 15%. However, even after the
      exclusion of tumors that were coded to the histology code 8162/3, Klatskin, age
      adjusted annual intrahepatic cholangiocarcinoma incidence increased during this
      period (APC = 4%, 95% confidence interval = 2% to 6%, P<.001).

PMID- 16788162
TI  - Expanding the scales: The multiple roles of MCH in regulating energy balance and
      other biological functions.
AB  - Melanin-concentrating hormone (MCH) is a cyclic peptide originally identified as
      a 17-amino-acid circulating hormone in teleost fish, where it is secreted by the
      pituitary in response to stress and environmental stimuli. In fish, MCH lightens
      skin color by stimulating aggregation of melanosomes, pigment-containing granules
      in melanophores, cells of neuroectodermal origin found in fish scales. Although
      the peptide structure between fish and mammals is highly conserved, in mammals,
      MCH has no demonstrable effects on pigmentation; instead, based on a series of
      pharmacological and genetic experiments, MCH has emerged as a critical
      hypothalamic regulator of energy homeostasis, having effects on both feeding
      behavior and energy expenditure.

PMID- 16788163
TI  - Molecular model of human CYP21 based on mammalian CYP2C5: structural features
      correlate with clinical severity of mutations causing congenital adrenal
      hyperplasia.
AB  - Enhanced understanding of structure-function relationships of human 21
      hydroxylase, CYP21, is required to better understand the molecular causes of
      congenital adrenal hyperplasia. To this end, a structural model of human CYP21
      was calculated based on the crystal structure of rabbit CYP2C5. All but two known
      allelic variants of missense type, a total of 60 disease-causing mutations and
      six normal variants, were analyzed using this model. A structural explanation for
      the corresponding phenotype was found for all but two mutants for which available
      clinical data are also discrepant with in vitro enzyme activity. Calculations of
      protein stability of modeled mutants were found to correlate inversely with the
      corresponding clinical severity. Putative structurally important residues were
      identified to be involved in heme and substrate binding, redox partner
      interaction, and enzyme catalysis using docking calculations and analysis of
      structurally determined homologous cytochrome P450s (CYPs). Functional and
      structural consequences of seven novel mutations, V139E, C147R, R233G, T295N,
      L308F, R366C, and M473I, detected in Scandinavian patients with suspected
      congenital adrenal hyperplasia of different severity, were predicted using
      molecular modeling. Structural features deduced from the models are in good
      correlation with clinical severity of CYP21 mutants, which shows the
      applicability of a modeling approach in assessment of new CYP21 mutations.

PMID- 16788164
TI  - "Bits" and pieces.
AB  - Many protein-protein interactions involved in signal transduction occur through
      the interaction of modular protein domains in one molecule with short linear
      sequences of amino acids ("motifs") in another. Although protein domains are
      recognized by a variety of computational tools, bioinformatic approaches alone
      have not been successful in identifying the short sequence motifs to which
      domains bind. A new approach, applying motif-determining algorithms to smaller
      subproteomic collections of proteins that are already known to associate with
      each other in high-throughput protein-protein interaction screens, now appears to
      be capable of capturing a reasonably large number of low-affinity core motif
      sequences. Application of this approach to the genomes of yeast, fruit flies,
      nematodes, and humans has doubled the number of known or suspected protein
      protein interaction motifs.

PMID- 16788165
TI  - General pathway for turning on promoters transcribed by RNA polymerases
      containing alternative sigma factors.

PMID- 16788166
TI  - Vibrio2005: the First International Conference on the Biology of Vibrios.

PMID- 16788167
TI  - The phage meeting: Classical venue, new momentum.

PMID- 16788168
TI  - Genomic analysis of carbon source metabolism of Shewanella oneidensis MR-1:
      Predictions versus experiments.
AB  - Genomic sequences have been used to find the genetic foundation for carbon source
      metabolism in Shewanella oneidensis MR-1. Annotated S. oneidensis MR-1 gene
      products were examined for their sequence similarity to enzymes participating in
      pathways for utilization of carbon and energy as described in the BioCyc database
      (http://www.biocyc.org/) or in the primary literature. A picture emerges that
      relegates five- and six-carbon sugars to minor roles as carbon sources, whereas
      multiple pathways for utilization of up to three-carbon carbohydrates seem to be
      present. Capacity to utilize amino acids for carbon and energy is also present. A
      few contradictions emerged in which enzymes appear to be present by annotations
      but are not active in the cell according to physiological experiments.
      Annotations are based on close sequence similarity and will not reveal inactivity
      due to deleterious mutations or due to lack of coordination of regulation and
      transport. Genes for a few enzymes known by experiment to be active are not found
      in the genome. This may be due to extensive divergence after duplication or
      convergence of function in separate lines in evolution rendering activities
      undetectable by sequence similarity. To minimize false predictions from protein
      sequences, we have been conservative in predicting pathways. We did not predict
      any pathway when, although a partial pathway was seen it was composed largely of
      enzymes already accounted for in any other complete pathway. This is an example
      of how a biochemically oriented sequence analysis can generate questions and
      direct further experimental investigation.

PMID- 16788169
TI  - Involvement of Bacillus subtilis ClpE in CtsR degradation and protein quality
      control.
AB  - The heat-inducible CtsR regulon of Bacillus subtilis codes for three Clp proteins
      with chaperone or protease activity. While the importance of ClpC and ClpP has
      been elucidated for a wide range of cellular adaptation processes, this study
      deals with the physiological role of B. subtilis ClpE. Northern experiments and
      reporter gene analyses revealed that ClpE is essential both for efficient CtsR
      dependent gene derepression and for rerepression during heat stress. ClpEP was
      found to destabilize the global regulator CtsR after heat shock in vivo with
      different kinetics than ClpCP, which is known to degrade CtsR in vitro and in
      vivo upon heat stress. Furthermore, ClpE was localized at heat-generated
      inclusion bodies by electron microscopy. The comparison of radiolabeled
      aggregated protein fractions of wild-type and clpE mutant cells during heat
      stress displayed a significant delay of protein disaggregation in the absence of
      ClpE. A kinetic Western blotting approach confirmed the long-term residence of
      ClpE in the insoluble cell fraction rather than in the cytoplasmic fraction.
      These observations indicate the involvement of ClpE in global protein
      disaggregation. As a characteristic structural element of ClpE, the N-terminal
      zinc finger domain was proven to be essential for basal in vitro ATPase activity.

PMID- 16788170
TI  - Phosphorylation of the group A Streptococcal CovR response regulator causes
      dimerization and promoter-specific recruitment by RNA polymerase.
AB  - The group A streptococcus (GAS), Streptococcus pyogenes, is an important human
      pathogen that causes infections ranging in severity from self-limiting
      pharyngitis to severe invasive diseases that are associated with significant
      morbidity and mortality. The pathogenic effects of GAS are mediated by the
      expression of virulence factors, one of which is the hyaluronic acid capsule
      (encoded by genes in the has operon). The expression of these virulence factors
      is controlled by the CovR/S (CsrR/S) two-component regulatory system of GAS which
      regulates, directly or indirectly, the expression of about 15% of the genome.
      CovR is a member of the OmpR/PhoB family of transcriptional regulators. Here we
      show that phosphorylation by acetyl phosphate results in dimerization of CovR.
      Dimerization was not observed using a D53A mutant of CovR, indicating that D53 is
      the site of phosphorylation in CovR. Phosphorylation stimulated binding of CovR
      to a DNA fragment containing the promoter of the has operon (Phas) approximately
      twofold. Binding of CovR D53A mutant protein to Phas was indistinguishable from
      the binding of wild-type unphosphorylated CovR. In vitro transcription, using
      purified GAS RNA polymerase, showed that wild-type CovR repressed transcription,
      and repression was stimulated more than sixfold by phosphorylation. In the
      presence of RNA polymerase, binding at Phas of phosphorylated, but not
      unphosphorylated, CovR was stimulated about fourfold, which accounts for the
      difference in the effect of phosphorylation on repression versus DNA binding.
      Thus, regulation of Phas by CovR is direct, and the degree of repression of Phas
      is controlled by the phosphorylation of CovR.

PMID- 16788171
TI  - Growth phase-dependent regulation of the extracytoplasmic stress factor, sigmaE,
      by guanosine 3',5'-bispyrophosphate (ppGpp).
AB  - The sigma subunit of procaryotic RNA polymerases is responsible for specific
      promoter recognition and transcription initiation. In addition to the major sigma
      factor, sigma 70, in Escherichia coli, which directs most of the transcription in
      the cell, bacteria possess multiple, alternative sigma factors that direct RNA
      polymerase to distinct sets of promoters in response to environmental signals. By
      activating an alternative sigma factor, gene expression can be rapidly
      reprogrammed to meet the needs of the cell as the environment changes. Sigma
      factors are subject to multiple levels of regulation that control their levels
      and activities. The alternative sigma factor sigmaE in Escherichia coli is
      induced in response to extracytoplasmic stress. Here we demonstrate that sigmaE
      can also respond to signals other than extracytoplasmic stress. sigmaE activity
      increases in a growth phase-dependent manner as a culture enters stationary
      phase. The signaling pathway that activates sigmaE during entry into stationary
      phase is dependent upon the alarmone guanosine 3',5'-bispyrophosphate (ppGpp) and
      is distinct from the pathway that signals extracytoplasmic stress. ppGpp is the
      first cytoplasmic factor shown to control sigmaE activity, demonstrating that
      sigmaE can respond to internal signals as well as signals originating in the cell
      envelope. ppGpp is a general signal of starvation stress and is also required for
      activation of the sigmaS and sigma 54 alternative sigma factors upon entry into
      stationary phase, suggesting that this is a key mechanism by which alternative
      sigma factors can be activated in concert to provide a coordinated response to
      nutritional stress.

PMID- 16788172
TI  - Flavin adenine dinucleotide-dependent 4-phospho-D-erythronate dehydrogenase is
      responsible for the 4-phosphohydroxy-L-threonine pathway in vitamin B6
      biosynthesis in Sinorhizobium meliloti.
AB  - The vitamin B6 biosynthetic pathway in Sinorhizobium meliloti is similar to that
      in Escherichia coli K-12; in both organisms this pathway includes condensation of
      two intermediates, 1-deoxy-D-xylulose 5-phosphate and 4-phosphohydroxy-L
      threonine (4PHT). Here, we report cloning of a gene designated pdxR that
      functionally corresponds to the pdxB gene of E. coli and encodes a dye-linked
      flavin adenine dinucleotide-dependent 4-phospho-D-erythronate (4PE)
      dehydrogenase. This enzyme catalyzes the oxidation of 4PE to 3-hydroxy-4
      phosphohydroxy-alpha-ketobutyrate and is clearly different in terms of cofactor
      requirements from the pdxB gene product of E. coli, which is known to be an NAD
      dependent enzyme. Previously, we revealed that in S. meliloti IFO 14782, 4PHT is
      synthesized from 4-hydroxy-l-threonine and that this synthesis starts with
      glycolaldehyde and glycine. However, in this study, we identified a second 4PHT
      pathway in S. meliloti that originates exclusively from glycolaldehyde (the major
      pathway). Based on the involvement of 4PE in the 4PHT pathway, the incorporation
      of different samples of 13C-labeled glycolaldehyde into pyridoxine molecules was
      examined using 13C nuclear magnetic resonance spectroscopy. On the basis of the
      spectral analyses, the synthesis of 4PHT from glycolaldehyde was hypothesized to
      involve the following steps: glycolaldehyde is sequentially metabolized to D
      erythrulose, D-erythrulose 4-phosphate, and D-erythrose 4-phosphate by
      transketolase, kinase, and isomerase, respectively; and D-erythrose 4-phosphate
      is then converted to 4PHT by the conventional three-step pathway elucidated in E.
      coli, although the mechanism of action of the enzymes catalyzing the first two
      steps is different.

PMID- 16788173
TI  - Characterization of the StcE protease activity of Escherichia coli O157:H7.
AB  - The StcE zinc metalloprotease is secreted by enterohemorrhagic Escherichia coli
      (EHEC) O157:H7 and contributes to intimate adherence of this bacterium to host
      cells, a process essential for mammalian colonization. StcE has also been shown
      to localize the inflammatory regulator C1 esterase inhibitor (C1-INH) to cell
      membranes. We tried to more fully characterize StcE activity to better understand
      its role in EHEC pathogenesis. StcE was active at pH 6.1 to 9.0, in the presence
      of NaCl concentrations ranging from 0 to 600 mM, and at 4 degrees C to 55 degrees
      C. Interestingly, antisera against StcE or C1-INH did not eliminate StcE cleavage
      of C1-INH. Treatment of StcE with the proteases trypsin, chymotrypsin, human
      neutrophil elastase, and Pseudomonas aeruginosa elastase did not eliminate StcE
      activity against C1-INH. After StcE was kept at 23 degrees C for 65 days, it
      exhibited full proteolytic activity, and it retained 30% of its original activity
      after incubation for 8 days at 37 degrees C. Together, these results show the
      StcE protease is a stable enzyme that is probably active in the environment of
      the colon. Additionally, k(cat)/K(m) data showed that StcE proteolytic activity
      was 2.5-fold more efficient with the secreted mucin MUC7 than with the complement
      regulator C1-INH. This evidence supports a model which includes two roles for
      StcE during infection, in which StcE acts first as a mucinase and then as an anti
      inflammatory agent by localizing C1-INH to cell membranes.

PMID- 16788174
TI  - In vivo dissection of the Helicobacter pylori Fur regulatory circuit by genome
      wide location analysis.
AB  - Iron homeostasis is particularly important in pathogenic bacteria, which need to
      compete with the host for this essential cofactor. In Helicobacter pylori, a
      causative agent of several gastric pathologies, iron uptake and storage genes are
      regulated at the transcriptional level by the ferric uptake regulator Fur. The
      regulatory circuit of Fur has recently come under focus because of an intimate
      interlink with a broader regulatory network governing metal homeostasis, acidic
      response, and virulence. To dissect the Fur regulatory circuit and identify in
      vivo targets of regulation, we developed a genome-wide location analysis protocol
      which allowed the identification of 200 genomic loci bound by Fur as well as the
      investigation of the binding efficiency of the protein to these loci in response
      to iron. Comparative analysis with transcriptomes of wild-type and fur deletion
      mutant strains allowed the distinction between targets associated with Fur
      regulation and genes indirectly influenced by the fur mutation. The Fur regulon
      includes 59 genes, 25 of which appear to be positively regulated. A case study
      conducted by primer extension analysis of two oppositely regulated genes, hpn2
      and flaB, suggests that negative regulation as well as positive regulation occurs
      at the transcriptional level. Furthermore, the results revealed the existence of
      13 Fur targeted loci within polycistronic operons, which were associated with
      transcript deregulation in the fur mutant strain. This study provides a
      systematic insight of Fur regulation at the genome-wide level in H. pylori and
      points to regulatory functions extending beyond the classical Fur repression
      paradigm.

PMID- 16788175
TI  - Characterization of the primary starch utilization operon in the obligate
      anaerobe Bacteroides fragilis: Regulation by carbon source and oxygen.
AB  - The opportunistic pathogen Bacteroides fragilis is a commensal organism in the
      large intestine, where it utilizes both dietary and host-derived polysaccharides
      as a source of carbon and energy. In this study, a four-gene operon required for
      starch utilization was identified. The operon also was found to be oxygen
      responsive and thus was designated osu for oxygen-induced starch utilization. The
      first three genes in the operon were predicted to encode outer membrane proteins
      involved in starch binding, and a fourth gene, osuD, encoded an amylase involved
      in starch hydrolysis. Insertional mutation of the osuA gene (Omega osuA) resulted
      in the inability to utilize starch or glycogen and an insertional mutation into
      the osuD gene (Omega osuD) was severely impaired for growth on starch media.
      Transcriptional studies indicated that maltose, maltooligosaccharides, and starch
      were inducers of osu expression and that maltose was the strongest inducer. A
      transcriptional activator of osuABCD, OsuR, was identified and found to mediate
      maltose induction. The Omega osuA and Omega osuD mutants were able to grow on
      maltose but not starch, whereas a mutation in osuR abolished growth on both
      substrates, indicating that additional genes under the control of OsuR are needed
      for maltose utilization. The osuABCD operon also was induced by exposure to
      oxygen and was shown to be part of the oxidative stress response important for
      aerotolerance of B. fragilis. Transcriptional analyses showed that osuA was
      induced 20-fold by oxygen, but OsuR was not required for this activation.
      Analysis of osu mutants suggested that expression of the operon was important for
      survival during oxygen exposure but not to hydrogen peroxide stress.

PMID- 16788176
TI  - Staphylococcus aureus helicase but not Escherichia coli helicase stimulates S.
      aureus primase activity and maintains initiation specificity.
AB  - Bacterial primases are essential for DNA replication due to their role in
      polymerizing the formation of short RNA primers repeatedly on the lagging-strand
      template and at least once on the leading-strand template. The ability of
      recombinant Staphylococcus aureus DnaG primase to utilize different single
      stranded DNA templates was tested using oligonucleotides of the sequence 5'-CAGA
      (CA)5 XYZ (CA)3-3', where XYZ represented the variable trinucleotide. These
      experiments demonstrated that S. aureus primase synthesized RNA primers
      predominately on templates containing 5'-d(CTA)-3' or TTA and to a much lesser
      degree on GTA-containing templates, in contrast to results seen with the
      Escherichia coli DnaG primase recognition sequence 5'-d(CTG)-3'. Primer synthesis
      was initiated complementarily to the middle nucleotide of the recognition
      sequence, while the third nucleotide, an adenosine, was required to support
      primer synthesis but was not copied into the RNA primer. The replicative
      helicases from both S. aureus and E. coli were tested for their ability to
      stimulate either S. aureus or E. coli primase. Results showed that each bacterial
      helicase could only stimulate the cognate bacterial primase. In addition, S.
      aureus helicase stimulated the production of full-length primers, whereas E. coli
      helicase increased the synthesis of only short RNA polymers. These studies
      identified important differences between E. coli and S. aureus related to DNA
      replication and suggest that each bacterial primase and helicase may have adapted
      unique properties optimized for replication.

PMID- 16788177
TI  - Plasticity of the P junc promoter of ISEc11, a new insertion sequence of the
      IS1111 family.
AB  - We describe identification and functional characterization of ISEc11, a new
      insertion sequence that is widespread in enteroinvasive E. coli (EIEC), in which
      it is always present on the virulence plasmid (pINV) and very frequently also
      present on the chromosome. ISEc11 is flanked by subterminal 13-bp inverted
      repeats (IRs) and is bounded by 3-bp terminal sequences, and it transposes with
      target specificity without generating duplication of the target site. ISEc11 is
      characterized by an atypical transposase containing the DEDD motif of the
      Piv/MooV family of DNA recombinases, and it is closely related to the IS1111
      family. Transposition occurs by formation of minicircles through joining of the
      abutted ends and results in assembly of a junction promoter (P juncC) containing
      a -10 box in the interstitial sequence and a -35 box upstream of the right IR. A
      natural variant of ISEc11 (ISEc11p), found on EIEC pINV plasmids, contains a
      perfect duplication of the outermost 39 bp of the right end. Upon
      circularization, ISEc11p forms a junction promoter (P juncP) which, despite
      carrying -10 and -35 boxes identical to those of P juncC, exhibits 30-fold
      greater strength in vivo. The discovery of only one starting point in primer
      extension experiments rules out the possibility that there are alternative
      promoter sites within the 39-bp duplication. Analysis of in vitro-generated
      transcripts confirmed that at limiting RNA polymerase concentrations, the
      activity of P juncP is 20-fold higher than the activity of P juncC. These
      observations suggest that the 39-bp duplication might host cis-acting elements
      that facilitate the binding of RNA polymerase to the promoter.

PMID- 16788178
TI  - Cross-regulation of biphenyl- and salicylate-catabolic genes by two regulatory
      systems in Pseudomonas pseudoalcaligenes KF707.
AB  - Pseudomonas pseudoalcaligenes KF707 grows on biphenyl and salicylate as sole
      sources of carbon. The biphenyl-catabolic (bph) genes are organized as
      bphR1A1A2(orf3)A3A4BCX0X1X2X3D, encoding the enzymes for conversion of biphenyl
      to acetyl coenzyme A. In this study, the salicylate-catabolic (sal) gene cluster
      encoding the enzymes for conversion of salicylate to acetyl coenzyme A were
      identified 6.6-kb downstream of the bph gene cluster along with a second
      regulatory gene, bphR2. Both the bph and sal genes were cross-regulated
      positively and/or negatively by the two regulatory proteins, BphR1 and BphR2, in
      the presence or absence of the effectors. The BphR2 binding sequence exhibits
      homology with the NahR binding sequences in various naphthalene-degrading
      bacteria. Based on previous studies and the present study we propose a new
      regulatory model for biphenyl and salicylate catabolism in strain KF707.

PMID- 16788179
TI  - The ribulose monophosphate pathway substitutes for the missing pentose phosphate
      pathway in the archaeon Thermococcus kodakaraensis.
AB  - The ribulose monophosphate (RuMP) pathway, involving 3-hexulose-6-phosphate
      synthase (HPS) and 6-phospho-3-hexuloisomerase (PHI), is now recognized as a
      widespread prokaryotic pathway for formaldehyde fixation and detoxification.
      Interestingly, HPS and PHI homologs are also found in a variety of archaeal
      strains, and recent biochemical and genome analyses have raised the possibility
      that the reverse reaction of formaldehyde fixation, i.e., ribulose 5-phosphate
      (Ru5P) synthesis from fructose 6-phosphate, may function in the biosynthesis of
      Ru5P in some archaeal strains whose pentose phosphate pathways are imperfect. In
      this study, we have taken a genetic approach to address this possibility by using
      the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. This strain
      possesses a single open reading frame (TK0475) encoding an HPS- and PHI-fused
      protein. The recombinant HPS-PHI-fused enzyme exhibited the expected HPS and PHI
      activities in both directions (formaldehyde fixing and Ru5P synthesizing). The
      TK0475 deletion mutant Delta hps-phi-7A did not exhibit any growth in minimal
      medium, while growth of the mutant strain could be recovered by the addition of
      nucleosides to the medium. This auxotrophic phenotype together with the catalytic
      properties of the HPS-PHI-fused enzyme reveal that HPS and PHI are essential for
      the biosynthesis of Ru5P, the precursor of nucleotides, showing that the RuMP
      pathway is the only relevant pathway for Ru5P biosynthesis substituting for the
      classical pentose phosphate pathway missing in this archaeon.

PMID- 16788180
TI  - Isolation of a high-affinity functional protein complex between OmcA and MtrC:
      Two outer membrane decaheme c-type cytochromes of Shewanella oneidensis MR-1.
AB  - Shewanella oneidensis MR-1 is a facultatively anaerobic bacterium capable of
      using soluble and insoluble forms of manganese [Mn(III/IV)] and iron [Fe(III)] as
      terminal electron acceptors during anaerobic respiration. To assess the
      structural association of two outer membrane-associated c-type decaheme
      cytochromes (i.e., OmcA [SO1779] and MtrC [SO1778]) and their ability to reduce
      soluble Fe(III)-nitrilotriacetic acid (NTA), we expressed these proteins with a C
      terminal tag in wild-type S. oneidensis and a mutant deficient in these genes
      (i.e., Delta omcA mtrC). Endogenous MtrC copurified with tagged OmcA in wild-type
      Shewanella, suggesting a direct association. To further evaluate their possible
      interaction, both proteins were purified to near homogeneity following the
      independent expression of OmcA and MtrC in the Delta omcA mtrC mutant. Each
      purified cytochrome was confirmed to contain 10 hemes and exhibited Fe(III)-NTA
      reductase activity. To measure binding, MtrC was labeled with the multiuse
      affinity probe 4',5'-bis(1,3,2-dithioarsolan-2-yl)fluorescein (1,2
      ethanedithiol)2, which specifically associates with a tetracysteine motif
      engineered at the C terminus of MtrC. Upon titration with OmcA, there was a
      marked increase in fluorescence polarization indicating the formation of a high
      affinity protein complex (Kd < 500 nM) between MtrC and OmcA whose binding was
      sensitive to changes in ionic strength. Following association, the OmcA-MtrC
      complex was observed to have enhanced Fe(III)-NTA reductase specific activity
      relative to either protein alone, demonstrating that OmcA and MtrC can interact
      directly with each other to form a stable complex that is consistent with their
      role in the electron transport pathway of S. oneidensis MR-1.

PMID- 16788181
TI  - Erwinia carotovora subspecies produce duplicate variants of ExpR, LuxR homologs
      that activate rsmA transcription but differ in their interactions with N
      acylhomoserine lactone signals.
AB  - The N-acylhomoserine lactone (AHL) signaling system comprises a producing system
      that includes acylhomoserine synthase (AhlI, a LuxI homolog) and a receptor,
      generally a LuxR homolog. AHL controls exoprotein production in Erwinia
      carotovora and consequently the virulence for plants. In previous studies we
      showed that ExpR, a LuxR homolog, is an AHL receptor and that it activates
      transcription of rsmA, the gene encoding an RNA binding protein which is a global
      negative regulator of exoproteins and secondary metabolites. An unusual finding
      was that the transcriptional activity of ExpR was neutralized by AHL. We
      subsequently determined that the genomes of most strains of E. carotovora
      subspecies tested possess two copies of the expR gene: expR1, which was
      previously studied, and expR2, which was the focus of this study. Comparative
      analysis of the two ExpR variants of E. carotovora subsp. carotovora showed that
      while both variants activated rsmA transcription, there were significant
      differences in the patterns of their AHL interactions, the rsmA sequences to
      which they bound, and their relative efficiencies of activation of rsmA
      transcription. An ExpR2- mutant produced high levels of exoproteins and reduced
      levels of RsmA in the absence of AHL. This contrasts with the almost complete
      inhibition of exoprotein production and the high levels of RsmA production in an
      AhlI- mutant that was ExpR1-. Our results suggest that ExpR2 activity is
      responsible for regulating exoprotein production primarily by modulating the
      levels of an RNA binding protein.

PMID- 16788182
TI  - YtsJ has the major physiological role of the four paralogous malic enzyme
      isoforms in Bacillus subtilis.
AB  - The Bacillus subtilis genome contains several sets of paralogs. An extreme case
      is the four putative malic enzyme genes maeA, malS, ytsJ, and mleA. maeA was
      demonstrated to encode malic enzyme activity, to be inducible by malate, but also
      to be dispensable for growth on malate. We report systematic experiments to test
      whether these four genes ensure backup or cover different functions. Analysis of
      single- and multiple-mutant strains demonstrated that ytsJ has a major
      physiological role in malate utilization for which none of the other three genes
      could compensate. In contrast, maeA, malS, and mleA had distinct roles in malate
      utilization for which they could compensate one another. The four proteins
      exhibited malic enzyme activity; MalS, MleA, and MaeA exhibited 4- to 90-fold
      higher activities with NAD+ than with NADP+. YtsJ activity, in contrast, was 70
      fold higher with NADP+ than with NAD+, with Km values of 0.055 and 2.8 mM,
      respectively. lacZ fusions revealed strong transcription of ytsJ, twofold higher
      in malate than in glucose medium, but weak transcription of malS and mleA. In
      contrast, mleA was strongly transcribed in complex medium. Metabolic flux
      analysis confirmed the major role of YtsJ in malate-to-pyruvate interconversion.
      While overexpression of the NADP-dependent Escherichia coli malic enzyme MaeB did
      not suppress the growth defect of a ytsJ mutant on malate, overexpression of the
      transhydrogenase UdhA from E. coli partially suppressed it. These results suggest
      an additional physiological role of YtsJ beyond that of malate-to-pyruvate
      conversion.

PMID- 16788183
TI  - Acyl carrier protein synthases from gram-negative, gram-positive, and atypical
      bacterial species: Biochemical and structural properties and physiological
      implications.
AB  - Acyl carrier protein (ACP) synthase (AcpS) catalyzes the transfer of the 4'
      phosphopantetheine moiety from coenzyme A (CoA) onto a serine residue of apo-ACP,
      resulting in the conversion of apo-ACP to the functional holo-ACP. The holo form
      of bacterial ACP plays an essential role in mediating the transfer of acyl fatty
      acid intermediates during the biosynthesis of fatty acids and phospholipids. AcpS
      is therefore an attractive target for therapeutic intervention. In this study, we
      have purified and characterized the AcpS enzymes from Escherichia coli,
      Streptococcus pneumoniae, and Mycoplasma pneumoniae, which exemplify gram
      negative, gram-positive, and atypical bacteria, respectively. Our gel filtration
      column chromatography and cross-linking studies demonstrate that the AcpS enzyme
      from M. pneumoniae, like E. coli enzyme, exhibits a homodimeric structure, but
      the enzyme from S. pneumoniae exhibits a trimeric structure. Our biochemical
      studies show that the AcpS enzymes from M. pneumoniae and S. pneumoniae can
      utilize both short- and long-chain acyl CoA derivatives but prefer long-chain CoA
      derivatives as substrates. On the other hand, the AcpS enzyme from E. coli can
      utilize short-chain CoA derivatives but not the long-chain CoA derivatives
      tested. Finally, our biochemical studies show that M. pneumoniae AcpS is
      kinetically a very sluggish enzyme compared with those from E. coli and S.
      pneumoniae. Together, the results of these studies show that the AcpS enzymes
      from different bacterial species exhibit different native structures and
      substrate specificities with regard to the utilization of CoA and its
      derivatives. These findings suggest that AcpS from different microorganisms plays
      a different role in cellular physiology.

PMID- 16788184
TI  - A variation of the translation attenuation model can explain the inducible
      regulation of the pBC16 tetracycline resistance gene in Bacillus subtilis.
AB  - Expression of the tet resistance gene from plasmid pBC16 is induced by the
      antibiotic tetracycline, and induction is independent of the native promoter for
      the gene. The nucleotide sequence at the 5' end of the tet mRNA (the leader
      region) is predicted to assume a complex secondary structure that sequesters the
      ribosome binding site for the tet gene. A spontaneous, constitutively expressed
      tet gene variant contains a mutation predicted to provide the tet gene with a
      nonsequestered ribosome binding site. Lastly, comparable levels of tet mRNA can
      be demonstrated in tetracycline-induced and uninduced cells. These results are
      consistent with the idea that the pBC16 tet gene is regulated by translation
      attenuation, a model originally proposed to explain the inducible regulation of
      the cat and erm genes in gram-positive bacteria. As with inducible cat and erm
      genes, the pBC16 tet gene is preceded by a translated leader open reading frame
      consisting of a consensus ribosome binding site and an ATG initiation codon,
      followed by 19 sense codons and a stop codon. Mutations that block translation of
      cat and erm leaders prevent gene expression. In contrast, we show that mutations
      that block translation of the tet leader result in constitutive expression. We
      provide evidence that translation of the tet leader peptide coding region blocks
      tet expression by preventing the formation of a secondary-structure complex that
      would, in the absence of leader translation, expose the tet ribosome binding
      site. Tetracycline is proposed to induce tet by blocking or slowing leader
      translation. The results indicate that tet regulation is a variation of the
      translation attenuation model.

PMID- 16788185
TI  - Role of CheB and CheR in the complex chemotactic and aerotactic pathway of
      Azospirillum brasilense.
AB  - It has previously been reported that the alpha-proteobacterium Azospirillum
      brasilense undergoes methylation-independent chemotaxis; however, a recent study
      revealed cheB and cheR genes in this organism. We have constructed cheB, cheR,
      and cheBR mutants of A. brasilense and determined that the CheB and CheR proteins
      under study significantly influence chemotaxis and aerotaxis but are not
      essential for these behaviors to occur. First, we found that although cells
      lacking CheB, CheR, or both were no longer capable of responding to the addition
      of most chemoattractants in a temporal gradient assay, they did show a
      chemotactic response (albeit reduced) in a spatial gradient assay. Second, in
      comparison to the wild type, cheB and cheR mutants under steady-state conditions
      exhibited an altered swimming bias, whereas the cheBR mutant and the che operon
      mutant did not. Third, cheB and cheR mutants were null for aerotaxis, whereas the
      cheBR mutant showed reduced aerotaxis. In contrast to the swimming bias for the
      model organism Escherichia coli, the swimming bias in A. brasilense cells was
      dependent on the carbon source present and cells released methanol upon addition
      of some attractants and upon removal of other attractants. In comparison to the
      wild type, the cheB, cheR, and cheBR mutants showed various altered patterns of
      methanol release upon exposure to attractants. This study reveals a significant
      difference between the chemotaxis adaptation system of A. brasilense and that of
      the model organism E. coli and suggests that multiple chemotaxis systems are
      present and contribute to chemotaxis and aerotaxis in A. brasilense.

PMID- 16788187
TI  - Uracil salvage pathway in Lactobacillus plantarum: Transcription and genetic
      studies.
AB  - The uracil salvage pathway in Lactobacillus plantarum was demonstrated to be
      dependent on the upp-pyrP gene cluster. PyrP was the only high-affinity uracil
      transporter since a pyrP mutant no longer incorporated low concentrations of
      radioactively labeled uracil and had increased resistance to the toxic uracil
      analogue 5-fluorouracil. The upp gene encoded a uracil phosphoribosyltransferase
      (UPRT) enzyme catalyzing the conversion of uracil and 5-phosphoribosyl-alpha-1
      pyrophosphate to UMP and pyrophosphate. Analysis of mutants revealed that UPRT is
      a major cell supplier of UMP synthesized from uracil provided by preformed
      nucleic acid degradation. In a mutant selection study, seven independent upp
      mutants were isolated and all were found to excrete low amounts of pyrimidines to
      the growth medium. Pyrimidine-dependent transcription regulation of the
      biosynthetic pyrimidine pyrR1-B-C-Aa1-Ab1-D-F-E operon was impaired in the upp
      mutants. Despite the fact that upp and pyrP are positioned next to each other on
      the chromosome, they are not cotranscribed. Whereas pyrP is expressed as a
      monocistronic message, the upp gene is part of the lp_2376-glyA-upp operon. The
      lp_2376 gene encodes a putative protein that belongs to the conserved protein
      family of translation modulators such as Sua5, YciO, and YrdC. The glyA gene
      encodes a putative hydroxymethyltransferase involved in C1 unit charging of
      tetrahydrofolate, which is required in the biosynthesis of thymidylate,
      pantothenate, and purines. Unlike upp transcription, pyrP transcription is
      regulated by exogenous pyrimidine availability, most likely by the same mechanism
      of transcription attenuation as that of the pyr operon.

PMID- 16788186
TI  - Comparison of the RpoH-dependent regulon and general stress response in Neisseria
      gonorrhoeae.
AB  - In the gammaproteobacteria the RpoH regulon is often equated with the stress
      response, as the regulon contains many of the genes that encode what have been
      termed heat shock proteins that deal with the presence of damaged proteins.
      However, the betaproteobacteria primarily utilize the HrcA repressor protein to
      control genes involved in the stress response. We used genome-wide
      transcriptional profiling to compare the RpoH regulon and stress response of
      Neisseria gonorrhoeae, a member of the betaproteobacteria. To identify the
      members of the RpoH regulon, a plasmid-borne copy of the rpoH gene was
      overexpressed during exponential-phase growth at 37 degrees C. This resulted in
      increased expression of 12 genes, many of which encode proteins that are involved
      in the stress response in other species. The putative promoter regions of many of
      these up-regulated genes contain a consensus RpoH binding site similar to that of
      Escherichia coli. Thus, it appears that unlike other members of the
      betaproteobacteria, N. gonorrhoeae utilizes RpoH, and not an HrcA homolog, to
      regulate the stress response. In N. gonorrhoeae exposed to 42 degrees C for 10
      min, we observed a much broader transcriptional response involving 37
      differentially expressed genes. Genes that are apparently not part of the RpoH
      regulon showed increased transcription during heat shock. A total of 13 genes
      were also down-regulated. From these results we concluded that although RpoH acts
      as the major regulator of protein homeostasis, N. gonorrhoeae has additional
      means of responding to temperature stress.

PMID- 16788188
TI  - Protein-protein interactions among Helicobacter pylori cag proteins.
AB  - Many Helicobacter pylori isolates contain a 40-kb region of chromosomal DNA known
      as the cag pathogenicity island (PAI). The risk for development of gastric cancer
      or peptic ulcer disease is higher among humans infected with cag PAI-positive H.
      pylori strains than among those infected with cag PAI-negative strains. The cag
      PAI encodes a type IV secretion system that translocates CagA into gastric
      epithelial cells. To identify Cag proteins that are expressed by H. pylori during
      growth in vitro, we compared the proteomes of a wild-type H. pylori strain and an
      isogenic cag PAI deletion mutant using two-dimensional difference gel
      electrophoresis (2D-DIGE) in multiple pH ranges. Seven Cag proteins were
      identified by this approach. We then used a yeast two-hybrid system to detect
      potential protein-protein interactions among 14 Cag proteins. One heterotypic
      interaction (CagY/7 with CagX/8) and two homotypic interactions (involving H.
      pylori VirB11/ATPase and Cag5) were similar to interactions previously reported
      to occur among homologous components of the Agrobacterium tumefaciens type IV
      secretion system. Other interactions involved Cag proteins that do not have known
      homologues in other bacterial species. Biochemical analysis confirmed selected
      interactions involving five of the proteins that were identified by 2D-DIGE.
      Protein-protein interactions among Cag proteins are likely to have an important
      role in the assembly of the H. pylori type IV secretion apparatus.

PMID- 16788189
TI  - Regulation of type IV fimbrial biogenesis in Dichelobacter nodosus.
AB  - Type IV fimbriae are expressed by several bacterial pathogens and are essential
      for virulence in Dichelobacter nodosus, which causes ovine footrot. We have
      identified a two-component signal transduction system (PilR/S) and an alternative
      sigma factor (sigma 54) that were shown by insertional inactivation to be
      required for the regulation of fimbrial biogenesis in D. nodosus. Western blots
      showed that in both pilR and rpoN mutants, fimbrial subunit production was
      significantly reduced by a process that was shown to occur at a PilR- and sigma
      54-dependent promoter. The mutants lacked surface fimbriae, which were shown to
      be required for the adherence of D. nodosus cells to tissue culture monolayers.
      The reduction in fimbrial subunit production in these mutants also resulted in a
      concomitant loss of the ability to secrete extracellular proteases. A maltose
      binding protein-PilR fusion protein was purified and was shown to bind
      specifically to a region located 234 to 594 bp upstream of the fimA
      transcriptional start point. To determine additional targets of PilR and sigma
      54, genome-wide transcriptional profiling was performed using a whole-genome
      oligonucleotide microarray. The results indicated that PilR and sigma 54
      regulated genes other than fimA; these genes appear to encode surface-exposed
      proteins whose role in virulence is unknown. In conclusion, this study represents
      a significant advancement in our understanding of how the ability of D. nodosus
      to cause ovine footrot is regulated, as we have shown that the biogenesis of type
      IV fimbriae in D. nodosus is regulated by a sigma 54-dependent PilR/S system that
      also indirectly controls protease secretion.

PMID- 16788190
TI  - Coregulation by phenylacetyl-coenzyme A-responsive PaaX integrates control of the
      upper and lower pathways for catabolism of styrene by Pseudomonas sp. strain Y2.
AB  - The P(styA) promoter of Pseudomonas sp. strain Y2 controls expression of the
      styABCD genes, which are required for the conversion of styrene to phenylacetate,
      which is further catabolized by the products of two paa gene clusters. Two PaaX
      repressor proteins (PaaX1 and PaaX2) regulate transcription of the paa gene
      clusters of this strain. In silico analysis of the P(styA) promoter region
      revealed a sequence located just within styA that is similar to the reported PaaX
      binding sites of Escherichia coli and the proposed PaaX binding sites of the paa
      genes of Pseudomonas species. Here we show that protein extracts from some
      Pseudomonas strains that have paaX genes, but not from a paaX mutant strain, can
      bind and retard the migration of a P(styA) specific probe. Purified maltose
      binding protein (MBP)-PaaX1 fusion protein specifically binds the P(styA)
      promoter proximal PaaX site, and this binding is eliminated by the addition of
      phenylacetyl-coenzyme A. The sequence protected by MBP-PaaX1 binding was defined
      by DNase I footprinting. Moreover, MBP-PaaX1 represses transcription from the
      P(styA) promoter in a phenylacetyl-coenzyme A-dependent manner in vitro. Finally,
      the inactivation of both paaX gene copies of Pseudomonas sp. strain Y2 leads to a
      higher level of transcription from the P(styA) promoter, while heterologous
      expression of the PaaX1 in E. coli greatly decreases transcription from the
      P(styA) promoter. These findings reveal a control mechanism that integrates
      regulation of styrene catabolism by coordinating the expression of the styrene
      upper catabolic operon to that of the paa-encoded central pathway and support a
      role for PaaX as a major regulatory protein in the phenylacetyl-coenzyme A
      catabolon through its response to the levels of this central metabolite.

PMID- 16788191
TI  - A pair of iron-responsive genes encoding protein kinases with a Ser/Thr kinase
      domain and a His kinase domain are regulated by NtcA in the Cyanobacterium
      Anabaena sp. strain PCC 7120.
AB  - The filamentous cyanobacterium Anabaena sp. strain PCC 7120 can fix N(2) when
      combined nitrogen is not available in the growth medium. It has a family of 13
      genes encoding proteins with both a Ser/Thr kinase domain and a His kinase
      domain. The function of these enzymes is unknown. Two of them are encoded by
      pkn41 (alr0709) and pkn42 (alr0710). These two genes are separated by only 72 bp
      on the chromosome, and our results indicate that they are cotranscribed. The
      expression of pkn41 and pkn42 is induced by iron deprivation irrespective of the
      nature of the nitrogen source. Mutants inactivating either pkn41, pkn42, or both
      grow similarly to the wild type under normal conditions, but their growth is
      impaired either in the presence of an iron chelator or under conditions of
      nitrogen fixation and iron limitation, two situations where the demand for iron
      is particularly strong. Consistent with these results, these mutants display
      lower iron content than the wild type and a higher level of expression for nifJ1
      and nifJ2, which encode pyruvate:ferredoxin oxidoreductases. Both nifJ1 and nifJ2
      are known to be induced by iron limitation. NtcA, a global regulatory factor for
      different metabolic pathways, binds to the putative promoter region of pkn41, and
      the induction of pkn41 in response to iron limitation no longer occurs in an ntcA
      mutant. Our results suggest that ntcA not only regulates the expression of genes
      involved in nitrogen and carbon metabolism but also coordinates iron acquisition
      and nitrogen metabolism by activating the expression of pkn41 and pkn42.

PMID- 16788192
TI  - Arginine homeostasis in J774.1 macrophages in the context of Mycobacterium bovis
      BCG infection.
AB  - The competition for L-arginine between the inducible nitric oxide synthase and
      arginase contributes to the outcome of several parasitic and bacterial
      infections. The acquisition of L-arginine, however, is important not only for the
      host cells but also for the intracellular pathogen. In this study we observe that
      strain AS-1, the Mycobacterium bovis BCG strain lacking the Rv0522 gene, which
      encodes an arginine permease, perturbs l-arginine metabolism in J774.1 murine
      macrophages. Infection with AS-1, but not with wild-type BCG, induced l-arginine
      uptake in J774.1 cells. This increase in L-arginine uptake was independent of
      activation with gamma interferon plus lipopolysaccharide and correlated with
      increased expression of the MCAT1 and MCAT2 cationic amino acid transport genes.
      AS-1 infection also enhanced arginase activity in resting J774.1 cells. Survival
      studies revealed that AS-1 survived better than BCG within resting J774.1 cells.
      Intracellular growth of AS-1 was further enhanced by inhibiting arginase and
      ornithine decarboxylase activities in J774.1 cells using L-norvaline and
      difluoromethylornithine treatment, respectively. These results suggest that the
      arginine-related activities of J774.1 macrophages are affected by the arginine
      transport capacity of the infecting BCG strain. The loss of Rv0522 gene-encoded
      arginine transport may have induced other cationic amino acid transport systems
      during intracellular growth of AS-1, allowing better survival within resting
      macrophages.

PMID- 16788193
TI  - Polar localization of the autotransporter family of large bacterial virulence
      proteins.
AB  - Autotransporters are an extensive family of large secreted virulence-associated
      proteins of gram-negative bacteria. Secretion of such large proteins poses unique
      challenges to bacteria. We demonstrate that autotransporters from a wide variety
      of rod-shaped pathogens, including IcsA and SepA of Shigella flexneri, AIDA-I of
      diffusely adherent Escherichia coli, and BrkA of Bordetella pertussis, are
      localized to the bacterial pole. The restriction of autotransporters to the pole
      is dependent on the presence of a complete lipopolysaccharide (LPS), consistent
      with known effects of LPS composition on membrane fluidity. Newly synthesized and
      secreted BrkA is polar even in the presence of truncated LPS, and all
      autotransporters examined are polar in the cytoplasm prior to secretion.
      Together, these findings are consistent with autotransporter secretion occurring
      at the poles of rod-shaped gram-negative organisms. Moreover, NalP, an
      autotransporter of spherically shaped Neisseria meningitidis contains the
      molecular information to localize to the pole of Escherichia coli. In N.
      meningitidis, NalP is secreted at distinct sites around the cell. These data are
      consistent with a model in which the secretion of large autotransporters occurs
      via specific conserved pathways located at the poles of rod-shaped bacteria, with
      profound implications for the underlying physiology of the bacterial cell and the
      nature of bacterial pathogen-host interactions.

PMID- 16788194
TI  - FppA, a novel Pseudomonas aeruginosa prepilin peptidase involved in assembly of
      type IVb pili.
AB  - Several subclasses of type IV pili have been described according to the
      characteristics of the structural prepilin subunit. Whereas molecular mechanisms
      of type IVa pilus assembly have been well documented for Pseudomonas aeruginosa
      and involve the PilD prepilin peptidase, no type IVb pili have been described in
      this microorganism. One subclass of type IVb prepilins has been identified as the
      Flp prepilin subfamily. Long and bundled Flp pili involved in tight adherence
      have been identified in Actinobacillus actinomycetemcomitans, for which assembly
      was due to a dedicated machinery encoded by the tad-rcp locus. A similar flp-tad
      rcp locus containing flp, tad, and rcp gene homologues was identified in the P.
      aeruginosa genome. The function of these genes has been investigated, which
      revealed their involvement in the formation of extracellular Flp appendages. We
      also identified a gene (designated by open reading frame PA4295) outside the flp
      tad-rcp locus, that we named fppA, encoding a novel prepilin peptidase. This is
      the second enzyme of this kind found in P. aeruginosa; however, it appears to be
      truncated and is similar to the C-terminal domain of the previously characterized
      PilD peptidase. In this study, we show that FppA is responsible for the
      maturation of the Flp prepilin and belongs to the aspartic acid protease family.
      We also demonstrate that FppA is required for the assembly of cell surface
      appendages that we called Flp pili. Finally, we observed an Flp-dependent
      bacterial aggregation process on the epithelial cell surface and an increased
      biofilm phenotype linked to Flp pilus assembly.

PMID- 16788195
TI  - Spx is a global effector impacting stress tolerance and biofilm formation in
      Staphylococcus aureus.
AB  - In Bacillus subtilis, Spx was recently characterized as a novel type of global
      regulator whose activity is regulated by the redox status of the cells. In the
      present study, we demonstrate that inactivation of Spx in the important pathogen
      Staphylococcus aureus renders the cells hypersensitive to a wide range of stress
      conditions including high and low temperature, high osmolarity, and hydrogen
      peroxide. Moreover, growth was restricted under nonstress conditions. Two
      dimensional gel electrophoresis revealed that the proteome of the spx mutant
      differs substantially from the proteome of wild-type cells, supporting the
      finding that Spx is also a global regulator in S. aureus. More specifically, we
      demonstrated that Spx is required for transcription of trxB, encoding thioredoxin
      reductase, under all growth conditions examined. As trxB is essential in S.
      aureus, we speculate that the severely reduced trxB transcription could account
      for some of the growth defects of the spx mutant. Inactivation of spx also
      enhanced biofilm formation. S. aureus biofilm formation is associated with the
      production of the polysaccharide intercellular adhesin encoded by the ica operon.
      Interestingly, our data indicate that the augmented capacity of the spx mutant to
      form biofilms is due to Spx modulating the expression of icaR, encoding a
      repressor of the structural ica genes (icaABCD). In summary, we conclude that Spx
      fulfills an important role for growth, general stress protection, and biofilm
      formation in S. aureus.

PMID- 16788196
TI  - The conjugative transposon Tn5397 has a strong preference for integration into
      its Clostridium difficile target site.
AB  - Tn5397 is a conjugative transposon, originally isolated from Clostridium
      difficile. The Tn5397 transposase TndX is related to the phage-encoded serine
      integrases and the Clostridium perfringens Tn4451 transposase TnpX. TndX is
      required for the insertion and excision of the transposon. Tn5397 inserts at one
      locus, attB(Cd), in C. difficile but at multiple sites in Bacillus subtilis.
      Apart from a conserved 5' GA dinucleotide at the recombination site, there
      appears to be little sequence conservation between the known target sites. To
      test the target site preference of Tn5397, attB(Cd) was introduced into the B.
      subtilis genome. When Tn5397 was transferred into this strain, 100% of the 50
      independent transconjugants tested had Tn5397 inserted into attB(Cd). This
      experiment was repeated using a 50-bp attB(Cd) with no loss of target preference.
      The mutation of the 5' GA to 5' TC in the attB(Cd) target site caused a switch in
      the polarity of insertion of Tn5397, which is consistent with this dinucleotide
      being at the crossover site and in keeping with the mechanism of other serine
      recombinases. Tn5397 could also transpose into 50-bp sequences encoding the end
      joints attL and attR but, surprisingly, could not recombine into the circular
      joint of Tn5397, attTn. Purified TndX was shown to bind specifically to 50-bp
      attB(Cd), attL, attR, attTn, and attB(Bs)(3) with relative binding affinities
      attTn approximately attR > attL > attB(Cd) > attB(Bs3). We conclude that TndX has
      a strong preference for attB(Cd) over other potential recombination sites in the
      B. subtilis genome and therefore behaves as a site-specific recombinase.

PMID- 16788198
TI  - FixJ: a major regulator of the oxygen limitation response and late symbiotic
      functions of Sinorhizobium meliloti.
AB  - Sinorhizobium meliloti exists either in a free-living state in the soil or in
      symbiosis within legume nodules, where the bacteria differentiate into nitrogen
      fixing bacteroids. Expression of genes involved in nitrogen fixation and
      associated respiration is governed by two intermediate regulators, NifA and FixK,
      respectively, which are controlled by a two-component regulatory system FixLJ in
      response to low-oxygen conditions. In order to identify the FixLJ regulon, gene
      expression profiles were determined in microaerobic free-living cells as well as
      during the symbiotic life of the bacterium for the wild type and a fixJ null
      mutant strain. We identified 122 genes activated by FixJ in either state,
      including 87 novel targets. FixJ controls 74% of the genes induced in
      microaerobiosis (2% oxygen) and the majority of genes expressed in mature
      bacteroids. Ninety-seven percent of FixJ-activated genes are located on the
      symbiotic plasmid pSymA. Transcriptome profiles of a nifA and a fixK mutant
      showed that NifA activates a limited number of genes, all specific to the
      symbiotic state, whereas FixK controls more than 90 genes, involved in free
      living and/or symbiotic life. This study also revealed that FixJ has no other
      direct targets besides those already known. FixJ is involved in the regulation of
      functions such as denitrification or amino acid/polyamine metabolism and
      transport. Mutations in selected novel FixJ targets did not affect the ability of
      the bacteria to form nitrogen-fixing nodules on Medicago sativa roots. From these
      results, we propose an updated model of the FixJ regulon.

PMID- 16788197
TI  - Transcriptional regulation of the Borrelia burgdorferi antigenically variable
      VlsE surface protein.
AB  - The Lyme disease agent Borrelia burgdorferi can persistently infect humans and
      other animals despite host active immune responses. This is facilitated, in part,
      by the vls locus, a complex system consisting of the vlsE expression site and an
      adjacent set of 11 to 15 silent vls cassettes. Segments of nonexpressed cassettes
      recombine with the vlsE region during infection of mammalian hosts, resulting in
      combinatorial antigenic variation of the VlsE outer surface protein. We now
      demonstrate that synthesis of VlsE is regulated during the natural mammal-tick
      infectious cycle, being activated in mammals but repressed during tick
      colonization. Examination of cultured B. burgdorferi cells indicated that the
      spirochete controls vlsE transcription levels in response to environmental cues.
      Analysis of PvlsE::gfp fusions in B. burgdorferi indicated that VlsE production
      is controlled at the level of transcriptional initiation, and regions of 5' DNA
      involved in the regulation were identified. Electrophoretic mobility shift assays
      detected qualitative and quantitative changes in patterns of protein-DNA
      complexes formed between the vlsE promoter and cytoplasmic proteins, suggesting
      the involvement of DNA-binding proteins in the regulation of vlsE, with at least
      one protein acting as a transcriptional activator.

PMID- 16788199
TI  - PopF1 and PopF2, two proteins secreted by the type III protein secretion system
      of Ralstonia solanacearum, are translocators belonging to the HrpF/NopX family.
AB  - Ralstonia solanacearum GMI1000 is a gram-negative plant pathogen which contains
      an hrp gene cluster which codes for a type III protein secretion system (TTSS).
      We identified two novel Hrp-secreted proteins, called PopF1 and PopF2, which
      display similarity to one another and to putative TTSS translocators, HrpF and
      NopX, from Xanthomonas spp. and rhizobia, respectively. They also show
      similarities with TTSS translocators of the YopB family from animal-pathogenic
      bacteria. Both popF1 and popF2 belong to the HrpB regulon and are required for
      the interaction with plants, but PopF1 seems to play a more important role in
      virulence and hypersensitive response (HR) elicitation than PopF2 under our
      experimental conditions. PopF1 and PopF2 are not necessary for the secretion of
      effector proteins, but they are required for the translocation of AvrA avirulence
      protein into tobacco cells. We conclude that PopF1 and PopF2 are type III
      translocators belonging to the HrpF/NopX family. The hrpF gene of Xanthomonas
      campestris pv. campestris partially restored HR-inducing ability to popF1 popF2
      mutants of R. solanacearum, suggesting that translocators of R. solanacearum and
      Xanthomonas are functionally conserved. Finally, R. solanacearum strain UW551,
      which does not belong to the same phylotype as GMI1000, also possesses two
      putative translocator proteins. However, although one of these proteins is
      clearly related to PopF1 and PopF2, the other seems to be different and related
      to NopX proteins, thus showing that translocators might be variable in R.
      solanacearum.

PMID- 16788200
TI  - Interactions between Streptomyces coelicolor and Bacillus subtilis: Role of
      surfactants in raising aerial structures.
AB  - Using mixed-species cultures, we have undertaken a study of interactions between
      two common spore-forming soil bacteria, Bacillus subtilis and Streptomyces
      coelicolor. Our experiments demonstrate that the development of aerial hyphae and
      spores by S. coelicolor is inhibited by surfactin, a lipopeptide surfactant
      produced by B. subtilis. Current models of aerial development by sporulating
      bacteria and fungi postulate a role for surfactants in reducing surface tension
      at air-liquid interfaces, thereby removing the major barrier to aerial growth. S.
      coelicolor produces SapB, an amphipathic peptide that is surface active and
      required for aerial growth on certain media. Loss of aerial hyphae in
      developmental mutants can be rescued by addition of purified SapB. While a
      surfactant from a fungus can substitute for SapB in a mutant that lacks aerial
      hyphae, not all surfactants have this effect. We show that surfactin is required
      for formation of aerial structures on the surface of B. subtilis colonies.
      However, in contrast to this positive role, our experiments reveal that surfactin
      acts antagonistically by arresting S. coelicolor aerial development and causing
      altered expression of developmental genes. Our observations support the idea that
      surfactants function specifically for a given organism regardless of their shared
      ability to reduce surface tension. Production of surfactants with antagonistic
      activity could provide a powerful competitive advantage during surface
      colonization and in competition for resources.

PMID- 16788201
TI  - Distinctive repertoire of contingency genes conferring mutation- based phase
      variation and combinatorial expression of surface lipoproteins in Mycoplasma
      capricolum subsp. capricolum of the Mycoplasma mycoides phylogenetic cluster.
AB  - The generation of surface variation among many divergent species of Mollicutes
      (mycoplasmas) occurs through stochastic expression patterns of diverse
      lipoprotein genes. The size and wide distribution of such variable gene sets in
      minimal (approximately 0.6- to 1.4-Mb) mycoplasmal genomes suggest their key role
      in the adaptation and survival of these wall-less monoderms. Diversity through
      variable genes is less clearly established among phylogenetically similar
      mycoplasmas, such as the Mycoplasma mycoides cluster of ruminant pathogens, which
      vary widely in host range and pathobiology. Using (i) genome sequences from two
      members of this clade, Mycoplasma capricolum subsp. capricolum and M. mycoides
      subsp. mycoides small colony biotype (SC), (ii) antibodies to specific peptide
      determinants of predicted M. capricolum subsp. capricolum gene products, and
      (iii) analysis of the membrane-associated proteome of M. capricolum subsp.
      capricolum, a novel set of six genes (vmcA to vmcF) expressing distinct Vmc
      (variable M. capricolum subsp. capricolum) lipoproteins is demonstrated. These
      occur at two separate loci in the M. capricolum subsp. capricolum genome, which
      shares striking overall similarity and gene synteny with the M. mycoides subsp.
      mycoides SC genome. Collectively, Vmc expression is noncoordinate and
      combinatorial, subject to a single-unit insertion/deletion in a 5' flanking
      dinucleotide repeat that governs expression of each vmc gene. All vmc genes share
      modular regions affecting expression and membrane translocation. In contrast,
      vmcA to vmcD genes at one locus express surface proteins with highly structured
      size-variable repeating domains, whereas vmcE to vmcF genes express products with
      short repeats devoid of predicted structure. These genes confer a distinctive,
      dynamic surface architecture that may represent adaptive differences within this
      important group of pathogens as well as exploitable diagnostic targets.

PMID- 16788202
TI  - Functional identification of conjugation and replication regions of the
      tetracycline resistance plasmid pCW3 from Clostridium perfringens.
AB  - Clostridium perfringens causes fatal human infections, such as gas gangrene, as
      well as gastrointestinal diseases in both humans and animals. Detailed molecular
      analysis of the tetracycline resistance plasmid pCW3 from C. perfringens has
      shown that it represents the prototype of a unique family of conjugative
      antibiotic resistance and virulence plasmids. We have identified the pCW3
      replication region by deletion and transposon mutagenesis and showed that the
      essential rep gene encoded a basic protein with no similarity to any known
      plasmid replication proteins. An 11-gene conjugation locus containing 5 genes
      that encoded putative proteins with similarity to proteins from the conjugative
      transposon Tn916 was identified, although the genes' genetic arrangements were
      different. Functional genetic studies demonstrated that two of the genes in this
      transfer clostridial plasmid (tcp) locus, tcpF and tcpH, were essential for the
      conjugative transfer of pCW3, and comparative analysis confirmed that the tcp
      locus was not confined to pCW3. The conjugation region was present on all known
      conjugative plasmids from C. perfringens, including an enterotoxin plasmid and
      other toxin plasmids. These results have significant implications for plasmid
      evolution, as they provide evidence that a nonreplicating Tn916-like element can
      evolve to become the conjugation locus of replicating plasmids that carry major
      virulence genes or antibiotic resistance determinants.

PMID- 16788203
TI  - EshA accentuates ppGpp accumulation and is conditionally required for antibiotic
      production in Streptomyces coelicolor A3(2).
AB  - Disruption of eshA, which encodes a 52-kDa protein that is produced late during
      the growth of Streptomyces coelicolor A3(2), resulted in elimination of
      actinorhodin production. In contrast, disruption of eshB, a close homologue of
      eshA, had no effect on antibiotic production. The eshA disruptant accumulated
      lower levels of ppGpp than the wild-type strain accumulated. The loss of
      actinorhodin production in the eshA disruptant was restored by expression of a
      truncated relA gene, which increased the ppGpp level to the level in the wild
      type strain, indicating that the reduced ppGpp accumulation in the eshA mutant
      was solely responsible for the loss of antibiotic production. Antibiotic
      production was also restored in the eshA mutant by introducing mutations into
      rpoB (encoding the RNA polymerase beta subunit) that bypassed the requirement for
      ppGpp, which is consistent with a role for EshA in modulating ppGpp levels. EshA
      contains a cyclic nucleotide-binding domain that is essential for its role in
      triggering actinorhodin production. EshA may provide new insights and
      opportunities to unravel the molecular signaling events that occur during
      physiological differentiation in streptomycetes.

PMID- 16788204
TI  - Site-directed amino acid substitutions in the hydroxylase alpha subunit of butane
      monooxygenase from Pseudomonas butanovora: Implications for substrates knocking
      at the gate.
AB  - Butane monooxygenase (BMO) from Pseudomonas butanovora has high homology to
      soluble methane monooxygenase (sMMO), and both oxidize a wide range of
      hydrocarbons; yet previous studies have not demonstrated methane oxidation by
      BMO. Studies to understand the basis for this difference were initiated by making
      single-amino-acid substitutions in the hydroxylase alpha subunit of butane
      monooxygenase (BMOH-alpha) in P. butanovora. Residues likely to be within
      hydrophobic cavities, adjacent to the diiron center, and on the surface of BMOH
      alpha were altered to the corresponding residues from the alpha subunit of sMMO.
      In vivo studies of five site-directed mutants were carried out to initiate
      mechanistic investigations of BMO. Growth rates of mutant strains G113N and L279F
      on butane were dramatically slower than the rate seen with the control P.
      butanovora wild-type strain (Rev WT). The specific activities of BMO in these
      strains were sevenfold lower than those of Rev WT. Strains G113N and L279F also
      showed 277- and 5.5-fold increases in the ratio of the rates of 2-butanol
      production to 1-butanol production compared to Rev WT. Propane oxidation by
      strain G113N was exclusively subterminal and led to accumulation of acetone,
      which P. butanovora could not further metabolize. Methane oxidation was
      measurable for all strains, although accumulation of 23 microM methanol led to
      complete inhibition of methane oxidation in strain Rev WT. In contrast, methane
      oxidation by strain G113N was not completely inhibited until the methanol
      concentration reached 83 microM. The structural significance of the results
      obtained in this study is discussed using a three-dimensional model of BMOH
      alpha.

PMID- 16788205
TI  - The crystal structure of beryllofluoride Spo0F in complex with the
      phosphotransferase Spo0B represents a phosphotransfer pretransition state.
AB  - A number of regulatory circuits in biological systems function through the
      exchange of phosphoryl groups from one protein to another. Spo0F and Spo0B are
      components of a phosphorelay that control sporulation in the bacterium Bacillus
      subtilis through the exchange of a phosphoryl group. Using beryllofluoride as a
      mimic for phosphorylation, we trapped the interaction of the phosphorylated Spo0F
      with Spo0B in the crystal lattice. The transition state of phosphoryl transfer
      continues to be a highly debated issue, as to whether it is associative or
      dissociative in nature. The geometry of Spo0F binding to Spo0B favors an
      associative mechanism for phosphoryl transfer. In order to visualize the
      autophosphorylation of the histidine kinase, KinA, and the subsequent phosphoryl
      transfer to Spo0F, we generated in silico models representing these reaction
      steps.

PMID- 16788206
TI  - GlnR-mediated regulation of nitrogen metabolism in Lactococcus lactis.
AB  - We show that the nitrogen regulatory protein GlnR of Lactococcus lactis represses
      transcription of the amtB-glnK, glnRA, and glnPQ operons. This likely occurs
      through a conserved DNA motif, 5'-TGTNA-7N-TNACAT-3', and takes place in response
      to extracellular glutamine and ammonium. GlnR-independent repression of amtB-glnK
      is mediated by the pleiotropic nitrogen regulator CodY.

PMID- 16788207
TI  - Analysis of the Anaplasma marginale major surface protein 1 complex protein
      composition by tandem mass spectrometry.
AB  - The protective major surface protein 1 (MSP1) complex of Anaplasma marginale is a
      heteromer of MSP1a and MSP1b, encoded by a multigene family. The msp1beta
      sequences were highly conserved throughout infection. However, liquid
      chromatography-tandem mass spectrometry analysis identified only a single MSP1b
      protein, MSP1b1, within the MSP1 complex.

PMID- 16788208
TI  - Involvement of Y-family DNA polymerases in mutagenesis caused by oxidized
      nucleotides in Escherichia coli.
AB  - Escherichia coli DNA polymerase IV incorporated 2-hydroxy-dATP opposite template
      guanine or thymine and 8-hydroxy-dGTP exclusively opposite adenine in vitro.
      Mutator phenotypes in sod/fur strains were substantially diminished by deletion
      of dinB and/or umuDC. DNA polymerases IV and V may be involved in mutagenesis
      caused by incorporation of the oxidized deoxynucleoside triphosphates.

PMID- 16788209
TI  - Interference between Streptococcus pneumoniae and Staphylococcus aureus: In vitro
      hydrogen peroxide-mediated killing by Streptococcus pneumoniae.
AB  - The bactericidal activity of Streptococcus pneumoniae toward Staphylococcus
      aureus is mediated by hydrogen peroxide. Catalase eliminated this activity.
      Pneumococci grown anaerobically or genetically lacking pyruvate oxidase (SpxB)
      were not bactericidal, nor were nonpneumococcal streptococci. These results
      provide a possible mechanistic explanation for the interspecies interference
      observed in epidemiologic studies.

PMID- 16788210
TI  - Role of the kidney in the metabolism of apolipoprotein A-IV: influence of the
      type of proteinuria.
AB  - Increased plasma concentrations of apolipoprotein A-IV (apoA-IV) in chronic renal
      disease suggest a metabolic role of the kidney for this antiatherogenic protein.
      Therefore, we investigated patients with various forms of proteinuria and found
      increased serum concentrations of apoA-IV in 124 nephrotic patients compared with
      274 controls (mean 21.9 +/- 9.6 vs. 14.4 +/- 4.0 mg/dl; P < 0.001). Decreasing
      creatinine clearance showed a strong association with increasing apoA-IV levels.
      However, serum albumin levels significantly modulated apoA-IV levels in patients
      with low creatinine clearance, resulting in lower levels of apoA-IV in patients
      with low compared with high albumin levels (21.4 +/- 8.6 vs. 29.2 +/- 8.4 mg/dl;
      P = 0.0007). Furthermore, we investigated urinary apoA-IV levels in an additional
      66 patients with a wide variety of proteinuria and 30 controls. Especially
      patients with a tubular type of proteinuria had significantly higher amounts of
      apoA-IV in urine than those with a pure glomerular type of proteinuria and
      controls (median 45, 14, and 0.6 ng/mg creatinine, respectively). We confirmed
      these results in affected members of a family with Dent's disease, who are
      characterized by an inherited protein reabsorption defect of the proximal tubular
      system. In summary, our data demonstrate that the increase of apoA-IV caused by
      renal impairment is significantly modulated by low levels of serum albumin as a
      measure for the severity of the nephrotic syndrome. From this investigation of
      apoA-IV in urine as well as earlier immunohistochemical studies, we conclude that
      apoA-IV is filtered through the normal glomerulus and is subsequently reabsorbed
      mainly by proximal tubular cells.

PMID- 16788211
TI  - ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway
      and associated with phagocytosis.
AB  - ABCA7 is highly homologous to ABCA1 and mediates cellular cholesterol and
      phospholipid release by apolipoproteins when transfected in vitro. However,
      expression of ABCA7 was downregulated by increased cellular cholesterol while
      ABCA1 was upregulated, and the results were consistent by forced expression or
      downregulation of sterol-responsive/regulatory element (SRE) binding proteins
      (SREBPs). We analyzed the promoter of the ABCA7 gene and identified the new exon
      encoding 96 bp (mouse) and 95 bp (human) of the 5' untranslated region and the
      transcription start site at 1,122 bp (mouse) and 1,260 bp (human) upstream of the
      initiation methionine codon. At 5' upstream of this exon is the ABCA7 proximal
      promoter containing multiple binding sites of transcription factors for
      hematopoiesis and SRE of 9 bp at 212 bp (mouse) and 179 bp (human) upstream of
      the new exon. The apolipoprotein A-I-mediated lipid release was not influenced by
      suppression of the endogenous ABCA7 with small interfering RNA in mouse
      fibroblasts or by its increase in ABCA1-deficient mouse cells. In contrast,
      phagocytic activity was altered in parallel to the ABCA7 expression in these
      cells. When phagocytosis was induced, the messages increased for SREBP2, ABCA7,
      and other SREBP2-regulated proteins. The ABCA1 message decreased in this
      condition. We conclude that the ABCA7 gene is regulated by sterol in the opposite
      direction to ABCA1 through SRE/SREBP2 and that expression of ABCA7 by this
      regulation is associated with phagocytic activity.

PMID- 16788213
TI  - The art of autopsy--time for a renaissance.

PMID- 16788212
TI  - Measurement of serum total glycerides and free glycerol by high-performance
      liquid chromatography.
AB  - Serum levels of total glycerides and free glycerol are important indices of lipid
      metabolism and cardiovascular disease risk. Convenient enzymatic methods of
      measurement have been available, but they are susceptible to interference.
      Situations exist in both research and clinical laboratories in which more
      specific and precise methods are needed. We developed HPLC methods for the
      measurement of serum total glycerides and free glycerol. For total glycerides,
      serum was mixed with an internal standard (1,2,4-butanetriol) and treated with
      alcoholic sodium hydroxide to hydrolyze glycerides to glycerol. After
      deproteinization with tungstic acid, the glycerol was benzoylated with an
      optimized Schotten-Baumann reaction and analyzed by HPLC. For free glycerol,
      serum was equilibrated with the internal standard and deproteinized with tungstic
      acid to remove the glycerides. The glycerol was benzoylated and analyzed as for
      total glycerol. Various factors were investigated, and no significant sources of
      interference were detected. The total coefficients of variation ranged from 0.7%
      to 2.0% for total glycerides and from 1.7% to 3.2% for free glycerol. The
      analytical recoveries ranged from 98.5% to 101.6%. In conclusion, simple and
      reliable HPLC methods for serum total glycerides and free glycerol have been
      developed. The methods may also be used for the analyses of glycerol or
      glycerides in other biological samples.

PMID- 16788214
TI  - Thiazolidinedione derivatives in type 2 diabetes mellitus.
AB  - In Europe, the thiazolidinedione derivatives pioglitazone and rosiglitazone have
      been approved for the treatment of type 2 diabetes mellitus either as monotherapy
      for patients with intolerance or contraindications to metformin or in combination
      therapy. This class of drugs seems particularly suited for obese patients, but is
      currently not considered as a first choice for monotherapy. The efficacy with
      respect to blood glucose lowering is comparable with sulphonylurea (SU)
      derivatives and with metformin. Long-term data with respect to efficacy and side
      effects are still limited.

PMID- 16788215
TI  - Antiviral treatment for chronic hepatitis B virus infection--immune modulation or
      viral suppression?
AB  - The availability of nucleoside analogues has broadened treatment options for
      chronic hepatitis B virus (HBV ) infection. Registered treatment for chronic
      hepatitis B currently consists of (pegylated) interferon, lamivudine and
      adefovir, while entecavir is expected to be licensed in the short term. Treatment
      is generally recommended for patients with high serum HBV DNA and elevated ALAT,
      indicating the host's immune response against HBV. Induction of an HBV -specific
      immune response seems crucial for persistent control of HBV infection. Currently
      available treatment strategies can be differentiated into those that provide
      sustained off-treatment response and those that provide therapy maintained
      response. A finite treatment course with immunomodulatory agents (interferon
      based therapy) results in sustained response in about one third of patients,
      while nucleoside analogue treatment generally requires indefinite therapy without
      a clear stopping point. Since nucleoside analogues are well tolerated, prolonged
      therapy is feasible, but a major drawback is the considerable risk of developing
      antiviral resistance, which occurs most frequently in lamivudine treated patients
      and to a lesser extent during adefovir or entecavir therapy. In our opinion,
      treatment with peginterferon should therefore be considered first-line therapy in
      eligible patients with a high likelihood of response based on serum HBV DNA, ALAT
      and HBV genotype. Patients not responding to PEG-IF N therapy or not eligible for
      peginterferon therapy should be treated with nucleos(t)ide analogues.

PMID- 16788216
TI  - Diagnostic errors; the need to have autopsies.
AB  - INTRODUCTION: In geriatric patients, atypical presentation and limitations in
      diagnostic scope may lead to underdiagnosis. The aim of this study was to
      establish the frequency, nature and causes of clinical diagnostic errors in a
      geriatric population. DESIGN: A retrospective study. METHODS: We assessed the
      accuracy of clinical diagnosis using autopsy results as our gold standard.
      Factors likely to influence accuracy of clinical diagnosis were identified. We
      used the (modified) classification of Goldman et al. to define discrepancy.
      RESULTS: We analysed 93 autopsies of a total of 331 deaths (28%). Discrepancies
      in major diagnoses were seen in 36 cases (39%). In 17 of these, clinical
      management might have been different if the diagnosis had been made premortem.
      These were: pulmonary embolism (4); unrecognised infection (4); intestinal
      ischaemia (3); ruptured aortic aneurysm (2); malignancy (1); tracheal obstruction
      (1); intestinal obstruction (1) and acute pancreatitis (1). Discrepancies in
      minor diagnoses were seen in 46 cases (50%). About one third of these were
      clinically relevant. Discrepancies occurred more frequently if there was a degree
      of uncertainty about clinical diagnosis p<0.001). CONCLUSION: Major discrepancies
      between clinical diagnosis and autopsy findings were seen in 39% of our study
      population. They occur more often in the case of uncertain clinical diagnosis.
      Our findings stress the continuing and important role of autopsy in improving
      clinical practice in geriatric medicine.

PMID- 16788218
TI  - Fatal aspiration of polyethylene glycol solution.
AB  - Endoscopy of the colon requires adequate cleansing of the entire bowel. Several
      laxative regimens have been propagated, but bowel preparation with polyethylene
      glycol (PEG) solution is popular because of the easy application and good
      cleansing results. Although very safe in daily use, complications of this bowel
      cleansing procedure have been reported and aspiration of the PEG solution is a
      possible and serious hazard. A case report is presented of a patient who
      aspirated the PEG solution and ultimately died because of respiratory failure.

PMID- 16788217
TI  - Helicobacter pylori antibiotic resistance in a Dutch region: trends over time.
AB  - AIM: Most patients treated for H. pylori infection receive empirical therapy
      based on epidemiological data of antibiotic resistance. However, previous
      European studies indicate that resistance patterns may be changing. Therefore,
      the aim of this study was to investigate the prevalence of primary clarithromycin
      and/or metronidazole resistant H. pylori strains over a six-year period (1997
      2002) in a regional hospital. METHODS: All patients visiting Slingeland Hospital
      in Doetinchem, the Netherlands between 1997 and 2002 with a positive H. pylori
      culture were included in this study. Susceptibility to metronidazole and
      clarithromycin was determined by disk diffusion. RESULTS: Of the 1355 patients
      with an H. pylori positive culture, 1127 did not have a history of H. pylori
      eradication, 58 did, and for 170 this information was not available. Mean rates
      of primary resistance to metronidazole and clarithromycin were 14.4% (162/1125)
      and 1.0% (11/1123), respectively. Primary metronidazole resistance was stable
      throughout the study period and primary clarithromycin resistance showed a
      decreasing trend. Patients of foreign descent and from secondary care had a
      higher chance of harbouring primary metronidazole-resistant H. pylori (adjusted
      OR (95% CI) 1.75 (1.1 to 2.8), and 1.60 (1.1 to 2.2), respectively). Patients
      with failed H. pylori eradication had a higher chance of harbouring metronidazole
      resistant H. pylori (43 vs 14%, p<0.0001) and clarithromycin-resistantH. pylori
      (5.3 vs 1.0%, p=0.004) than untreated patients. CONCLUSION: Primary metronidazole
      resistance is stableat a low level, while primary clarithromycin resistance
      isvirtually absent in the eastern part of the Netherlands.Therefore, triple
      therapy with a proton pump inhibitor,clarithromycin and amoxicillin can remain
      the empiricaltreatment of choice in the Netherlands.

PMID- 16788219
TI  - Multiple cysts in the liver autosomal dominant polycystic liver disease.
AB  - A 45-year-old woman was admitted because of abdominal pain and a feeling of
      fullness. Ultrasound and CT scan of the abdomen showed a massively enlarged liver
      with hundreds of cysts and displacement of the right kidney. There were no cysts
      in the kidneys. Because several members of her family also had multiple cysts in
      the liver, the diagnosis of autosomal dominant polycystic liver disease (PCLD)
      was made. Genetic analysis demonstrated a protein kinase C substrate 80 K-H (PR
      KCSH) gene mutation (1338-2A>G) and confirmed the clinical diagnosis. A brief
      review of the genetics and possible treatments is given.

PMID- 16788220
TI  - Status epilepticus caused by a myxoedema coma.
AB  - The case of a 63-year-old woman who presented with status epilepticus, coma and
      hypoventilation is reported. A primary neurological cause was considered.
      Hypothermia led to further investigations and a diagnosis of severe
      hypothyroidism. The neurological complications of hyperthyriodism include
      alteration in mental status with slowness, decreased concentration and lethargy,
      headache, cranial nerve palsies, dysarthria, hoarseness, myopathy, neuropathy,
      reflex changes, ataxia, and psychotic episodes. Our patient suffered from a rare
      consequence of severe hypothyroidism presenting with status epilepticus and she
      died despite treatment. To our knowledge this is the second patient to be
      reported with myxoedema coma with this kind of presentation. Despite therapeutic
      options, there is a high mortality rate.

PMID- 16788221
TI  - A young man with nonhealing venous ulcers.
AB  - A 35-year-old man presented with nonhealing ulcers at an atypical location on his
      left foot, caused by a combination of venous insufficiency (after deep venous
      thrombosis) and arterial insufficiency. The underlying cause was Buerger's
      disease.

PMID- 16788222
TI  - Yellow or orange hands as presenting signs of carotenaemia.

PMID- 16788225
TI  - Current cholera epidemics in west Africa and risks of imported cases in European
      countries.

PMID- 16788226
TI  - Is it time to introduce hepatitis A vaccine into routine childhood immunisations?

PMID- 16788227
TI  - Increase in viral meningitis cases reported in France, summer 2005.

PMID- 16788228
TI  - Legionnaires disease in southeast London.

PMID- 16788229
TI  - Changes to legislation designed to control TSEs discussed.

PMID- 16788231
TI  - Preparations for implementing human papillomavirus vaccination should begin.

PMID- 16788232
TI  - Fatal case of HUS after VTEC E. coli O145 infection in Slovenia highlights
      importance of testing for this rare strain.

PMID- 16788233
TI  - Monitoring CA-MRSA infections in Slovenia.

PMID- 16788234
TI  - EHEC O157 outbreak in Sweden from locally produced lettuce, August-September
      2005.

PMID- 16788235
TI  - Imported frozen raspberries cause a series of norovirus outbreaks in Denmark,
      2005.

PMID- 16788236
TI  - Salmonellosis outbreak linked to carpaccio made from imported raw beef, Denmark,
      June-August 2005.

PMID- 16788237
TI  - Japanese encephalitis outbreak in India and Nepal.

PMID- 16788238
TI  - Preventing introduction and spread of avian influenza among bird flocks in
      Europe: recommendations by European Animal Health Panel.

PMID- 16788239
TI  - Vaccination catch-up campaign in response to recent increase in Hib infection in
      Ireland.

PMID- 16788240
TI  - Lymphogranuloma venereum outbreak in men who have sex with men (MSM) in Belgium,
      January 2004 to July 2005.

PMID- 16788241
TI  - Andrea Infuso, coordinator of EuroTB, pioneer in European tuberculosis and HIV
      surveillance.

PMID- 16788243
TI  - Molecular detection of disseminated tumor cells in the peripheral blood of
      patients with gastric cancer: evaluation of their prognostic significance.
AB  - Early detection of disseminated tumor cells in the peripheral blood of patients
      with early stage gastric cancer could help to improve the outcome after tumor
      resection. The aim of this study is to evaluate the prognostic significance of
      tumor-related mRNA for the detection of circulating tumor cells in gastric cancer
      patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We
      simultaneously analyzed human telomerase reverse transcriptase (hTERT),
      cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA)
      mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer
      patients and 30 healthy individuals. Additionally, analyses were carried out for
      the correlation of these four molecular markers with patients' clinicopathologic
      features, as well as the occurrence of postoperative recurrence/metastasis. Among
      42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and
      CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42),
      respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA,
      while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA
      was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001),
      depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM
      stage (p<0.001). In addition, the multivariate logistic regression demonstrated
      that CEA mRNA expression was an independent and significant predictor for
      postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA
      may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of
      circulating cancer cells in gastric cancer patients' peripheral blood. Patients
      with positive CEA mRNA expression in peripheral blood have a significantly higher
      risk of postoperative recurrence/metastasis.

PMID- 16788244
TI  - Non classical HLA genes and non-HLA genes in a population of infants at familial
      risk of atopy.
AB  - AIM: We investigated on parental history and IgE serum level in 2588 consecutive
      newborns to individuate babies "at risk" of atopy at birth and we analysed the
      polymorphisms of class III region to evaluate the association with immunogenetic
      markers of HLA: C4A, C4B, LTA, RAGE and TNFA genes; we performed TNF and IgE
      receptor (FCERB1) physiologically related gene polymorphisms. RESULT: 791
      babies/2588 (30.6%) were considered "at risk" for atopy and followed-up: 400 had
      familial history of atopy (at least one parent or sibling), 256 had IgE >0.35
      kUA/l at birth and during the follow-up and 135 were positive for both
      conditions. The allele C4B2 was significantly more frequent in the sample of
      babies at risk (22.1% vs 10%, p< 0.001). Furthermore, the mean value of IgE at
      birth in babies carrying the allele C4B2 was 2.26 KUA/l versus 0.74 KUA/l in
      those not carrying this allele (p=0.01). No significant association emerged for
      RAGE at the centromeric end of class III region and for LTA, TNFA at the
      telomeric one. TNFRI, TNFRII and FCERB1 gene polymorphisms also seemed not
      implicated. CONCLUSION: Our study confirms that HLA class III region seems
      involved in familial predisposition to atopy, and C4B gene probably acts as a
      marker of a more restricted subregion.

PMID- 16788245
TI  - Altered beta-amyloid precursor protein isoforms in Mexican Alzheimer's Disease
      patients.
AB  - OBJECTIVE: To determine the beta-amyloid precursor protein (betaAPP) isoforms
      ratio as a risk factor for Alzheimer's Disease and to assess its relationship
      with demographic and genetic variables of the disease. METHODS: Blood samples
      from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46
      healthy control subjects were collected for Western blotting for betaAPP. A ratio
      of betaAPP isoforms, in optical densities, between the upper band (130 Kd) and
      the lower bands (106-110 Kd) was obtained. Odds ratios were obtained to determine
      risk factor of this component. RESULTS: betaAPP ratio on AD subjects was lower
      than that of control subjects: 0.3662 +/- 0.1891 vs. 0.6769 +/- 0.1021 (mean +/-
      SD, p<0.05). A low betaAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45-15.33).
      When onset of disease was taken into account, a betaAPP ratio on EOAD subjects of
      0.3965 +/- 0.1916 was found vs. 0.3445 +/- 0.1965 on LOAD subjects (p>0.05).
      CONCLUSIONS: Altered betaAPP isoforms is a high risk factor for Alzheimer's
      disease, although it has no influence on the time of onset of the disease.

PMID- 16788246
TI  - A comprehensive candidate gene study on bronchial asthma and juvenile idiopathic
      arthritis.
AB  - Bronchial asthma and juvenile idiopathic arthritis (JIA) are complex genetic
      diseases. As both represent chronic inflammatory diseases it is likely that they
      are at least partially influenced by the same genetic variants. One goal in
      dissecting the genetics of complex diseases is to identify a genetic risk
      profile. Therefore it is necessary to genotype polymorphisms in many different
      pathways. Thus we investigated 48 polymorphisms in 24 genes for association with
      asthma and/or JIA. Genotpying was performed on 231 asthmatic children, 86
      children with JIA and 270 controls. Association analysis was performed by the
      Armitage's trend test. Furthermore haplotypes were calculated by FAMHAP. We found
      association of polymorphisms within IL-4, CTLA4 and TNFalpha with asthma and/or
      JIA. Furthermore, the polymorphisms showed an inverse distribution between
      children with asthma and JIA. However, we were not able to confirm association of
      most of the previously described candidate genes. We conclude from our data that
      it might be very difficult to identify genetic risk profiles for the development
      of asthma and/or JIA that would be valid across different populations. However,
      this study adds further evidence that the common genetic background of asthma and
      JIA is mainly based on polymorphisms in important TH1 and TH2 cytokines.

PMID- 16788247
TI  - Serum levels of platelet released CD40 ligand are increased in early onset
      occlusive carotid artery disease.
AB  - OBJECTIVE: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator
      between inflammation and atherosclerosis, and the CD40-CD40L interaction has a
      role in atherosclerotic lesion progression. We evaluated if platelet released
      serum sCD40L and sCD40 levels differ between patients with early onset occlusive
      carotid artery disease and age-matched controls. METHODS: sCD40L and sCD40 levels
      were measured in serum samples of 60 patients with occlusive carotid artery
      disease and 30 age-matched controls using ELISA. Degree of stenosis of the
      internal carotid artery (ICA), and intima-media thickness (IMT) in the common
      carotid artery were measured by high resolution ultrasound. Values are given as
      mean +/- SD. RESULTS: Mean age was 50.9 +/- 3.5 and 50.1 +/- 3.5 years in the
      patient and control groups. IMT was significantly thicker in patients than in
      controls (0.89 +/- 0.14 vs. 0.78 +/-0.12 mm, p=0.0003). Serum levels of sCD40L
      were significantly higher (6.9 +/- 5 vs. 4.5 +/- 3.0 ng/mL, p=0.038) in patients,
      whereas sCD40 did not differ significantly between patients and controls (85 +/-
      56.9 vs. 79.3 +/- 18.7 pg/mL, p=0.34). IMT did not correlate with sCD40L or sCD40
      levels (R=-0.03, p=0.77; and R=0.109, p=0.308, respectively). CONCLUSIONS: sCD40L
      but not sCD40 levels are significantly higher in patients with occlusive carotid
      artery disease. Platelet derived sCD40L may be a key mediator among inflammation,
      thrombosis and atherosclerosis.

PMID- 16788248
TI  - Genetic polymorphisms of phase II metabolic enzymes and lung cancer
      susceptibility in a population of Central South China.
AB  - A case-control study was conducted for analyzing the genetic polymorphisms of
      phase II metabolic enzymes in 97 patients with lung cancer and 197 healthy
      subjects from Han ethnic group of Hunan Province located in Central South China.
      The results showed that the frequencies of glutathione S-transferase (GST) M1
      null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in
      lung cancer patients were significantly higher than those of the controls.
      Genotypes of combining GSTP1 mutant/GSTM1(-) or GSTP1 mutant/GSTT1(-) led to high
      risk of lung cancer. Individuals carrying any two or all three of GSTM1(-),
      GSTT1(-) and GSTP1 mutant genotypes have a distinctly increased risk of lung
      cancer when compared to those with GSTM1 present (GSTM1+: GSTM1+/+ or GSTM1+/-),
      GSTT1 present (GSTT1+: GSTT1+/+ or GSTT1+/-) and GSTP1 wild genotypes.
      Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2
      (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a
      remarkably higher lung cancer risk than those carrying combined NAT2 slow
      acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+)
      genotypes. All these findings suggest that the genetic polymorphisms of phase II
      metabolic enzymes affect the susceptibility of lung cancer in the Han ethnic
      group of Central South China.

PMID- 16788249
TI  - Potential biomarkers found by protein profiling may provide insight for the
      macrovascular pathogenesis of diabetes mellitus.
AB  - Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its
      pathogenesis is unclear. The purpose of this study was to find potential
      biomarkers to serve as indicators for the pathogenesis of DM in a time course
      manner. Based on our previous findings that oxidative stress occurred at week 8,
      aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control
      male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ
      injection. The protein profiles were studied employing surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry technology in attomole
      sensitivity range. In the aorta, a multiple biomarker panel was discovered at the
      4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3
      biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers
      were all discovered to have 100% classification accuracy rate to differentiate
      the DM and control groups at all time intervals. Besides, 2 biomarkers were also
      found to have high classification value at week 12. Comparing the aorta and sera
      from DM and non-DM rats, a bundle of potential biomarkers with significant
      changes in peak intensities and high classification values were found. Two of the
      serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS
      PROT knowledgebase. Validation has been conducted using immunoassay kits. These
      potential biomarkers may provide valuable insight on the pathogenesis of DM and
      macrovascular complications.

PMID- 16788250
TI  - C242T polymorphism in CYBA gene (p22phox) and risk of coronary artery disease in
      a population of Caucasian Italians.
AB  - BACKGROUND: specific polymorphisms of genes regulating intracellular redox
      balance and oxidative stress are related to atherogenesis. Some studies have
      identified a relationship between progression of atherosclerosis and C242T
      mutation in CYBA gene coding for p22phox, a subunit of the NADH/NADPH oxidase
      system. DESIGN: we investigated whether the C242T nucleotide transition is
      associated with the presence of coronary artery disease (CAD) in a population of
      494 Caucasian Italians undergoing coronary angiography to diagnose the cause of
      chest pain. RESULTS: the frequency of the T mutant allele that we found in 276
      patients with angiographically documented CAD was significantly higher compared
      to what we observed in 218 subjects with normal coronary arteries (Controls)
      (respectively: 0.400 and 0.332, p<0.01). The prevalence of the T allele was even
      stronger when we compared: 1) early onset (age < or =55) vs late onset (age > or
      =65) single-vessel CAD patients (respectively: 0.75 and 0.48, p<0.05), and 2) the
      subgroup of CAD patients with at least one > or =98% stenosis in a coronary
      vessel vs those with no > or =98% stenosis in a coronary vessel (respectively:
      0.425 and 0.365, p<0.05). CONCLUSIONS: these results support the increased risk
      of developing early CAD and of having rapid progression of coronary stenosis in
      subjects carrying the C242T nucleotide transition among the Italian population.

PMID- 16788251
TI  - Prognostic value of RT-PCR tyrosinase detection in peripheral blood of melanoma
      patients.
AB  - Malignant melanoma (MM) prognosis has been related to tumour thickness and
      clinical stage and metastasis risk has been associated with presence of tumour
      cells in peripheral blood. The aim of this study was to determine the
      relationship between presence of tyrosinase in peripheral blood of MM patients
      and their clinical prognosis. Blood samples from 58 MM patients (stage I-IV) were
      analysed, using RT-PCR assay to detect tyrosinase mRNA. The results showed that
      positive RT-PCR assay for tyrosinase were significantly associated with clinical
      status and tumour thickness. After a median follow-up of 24 months, RT-PCR
      results were found to be significant correlated with recurrence (p<0.05) and
      clinical stage III (p<0.05). Separate analysis of stage III tumours to determine
      the prognostic value of tyrosinase presence in peripheral blood showed an overall
      24-month survival rate of 70% in the RT-PCR negative group versus 10% in the
      positive group (p<0.02). These results suggest that detection of circulating
      melanoma cells may be especially relevant in stage III patients, in whom RT-PCR
      positivity defines a subpopulation at high risk of recurrence.

PMID- 16788253
TI  - The use of the coefficient of variation in detecting sincerity of effort: a meta
      analysis.
AB  - The coefficient of variation (CV) is used to determine sincerity of effort of
      strength measurements. However, there is a controversy in the literature
      concerning its validity and effectiveness. We used a meta-analytic approach and
      calculated the effect size between maximal and submaximal efforts for the CV of
      grip, elbow flexion and knee extension. We summarized findings concerning
      stability, sensitivity and specificity of the CV. We found large effect sizes (d
      > or = 0.8) for all comparisons indicating that submaximal efforts were more
      variable than maximal efforts. We also found large error rates and low stability
      of the CV. The error rates and stability values of the CV are unacceptable from
      both a clinical and a medico-legal standpoint. Therefore, the use of the CV for
      assessing sincerity of effort needs to be questioned.

PMID- 16788254
TI  - High incidence of disability pension with a psychiatric diagnosis in western
      Sweden. A population-based study from 1980 to 1998.
AB  - Regional differences in Sweden in the prevalence of disability pension with a
      psychiatric diagnosis are unexplained, in spite of the significant impact on the
      population's health, rehabilitation systems, and the health care system. The
      purpose of this study was to describe the pattern of disability pensions with a
      psychiatric diagnosis and to analyze the impact of age and gender. We examined
      the incidence rates in one urban and one semi-rural region and compared these to
      national rates. The study sample was drawn from employed persons between 16-64
      years of age who, because of their sickness insurance coverage, would be eligible
      to access disability pensions should it be necessary. Analysis of annual
      incidences and standardized morbidity ratios were made for 1980, 1985, 1990,
      1995, and 1998. Data on disability pension cases were collected from the National
      Social Insurance registers. In the urban region we found that the proportion of
      men and women clearly outnumbered the national average: approximately twice the
      number of persons between 16-64 years of age with a psychiatric diagnosis were
      receiving a disability pension. In the semi-rural region there were fewer men
      overall on disability pensions with psychiatric disorders, but in 1980, 1985, and
      1995 women clearly outnumbered men. Access to psychiatric care, unemployment,
      alcohol dependence, and previous sickness absence are suggested as possible
      factors that might affect the rates of disability pension in different
      geographical settings.

PMID- 16788255
TI  - Maximizing competence through professional development: increasing disability
      knowledge among One-Stop Career Center staff.
AB  - The Workforce Investment Act of 1998 (USA) mandates that partners in the One-Stop
      Career Center system be prepared to serve a diverse customer base. Effective
      service delivery depends in part on a focus on human resources and professional
      development. This article presents innovative strategies for One-Stop Career
      Center staff training related to serving customers with disabilities. Findings
      from case study research conducted in several One-Stops across the country
      revealed that staff struggled with both knowledge and attitudes around disability
      issues. To address these concerns, local leaders developed practices that
      provided opportunities to gain practical skills and put acquired knowledge to
      use. These included a formalized curriculum focused on disability issues;
      informal support and consultation from a disability specialist; and exposure and
      learning through internships for students with disabilities. Implications are
      offered to stimulate thinking and creativity in local One-Stops regarding the
      most effective ways to facilitate staff learning and, in turn, improve services
      for customers with disabilities.

PMID- 16788256
TI  - Effects of co-financed interdisciplinary teamwork on sick leave for people with
      musculoskeletal disorders.
AB  - AIMS: The aim of the study was to assess if health care centres with a co
      financing model for collaborative rehabilitation between primary health care,
      sickness insurance offices and social welfare offices reduced sick leave among
      persons with musculoskeletal disorders compared to health centres with
      conventional rehabilitation structures. METHOD: A comparative prospective study
      was conducted. Consecutive patients aged 16-64 with musculoskeletal disorders
      attending the health care centres with (n=107) and without (n=31) co-financing
      model were interviewed. In addition, we collected register data about patients'
      allowances for sick leave days for totally 18 months. RESULTS: The intervention
      group had an average of 94 days and the controls 87 days on sick leave during the
      12-months period after inclusion in the study. At 12 months the proportion of
      patients sick listed was 31% in the intervention group and 32% in the control
      group. CONCLUSION: The study could not show that the co-financing model reduced
      the numbers of sick leave days among patients with musculoskeletal disorders. A
      possible explanation for the lack of positive impact on patients' health or work
      ability might be that the working procedure has in fact not really been changed
      and the tool mix lack solid evidence. The study identifies some methodological
      problems addressed in future research trying to link organisational changes with
      patient outcomes.

PMID- 16788257
TI  - Assessment of Work Performance (AWP)--development of an instrument.
AB  - Adequate work assessments are a matter of importance both for individuals and
      society [5,29,31,38,40,46,52]. However, there is a lack of adequate and reliable
      instruments for use in work rehabilitation [14,15,20,21,31,44]. The purpose of
      this study was to develop and evaluate an observation instrument for assessing
      work performance, the AWP (Assessment of Work Performance). The purpose of the 14
      item instrument is to assess the individual's observable working skills in three
      different areas: motor skills, process skills, and communication and interaction
      skills. This article describes the development and results of preliminary testing
      of the AWP. The testing indicates a satisfactory face validity and utility for
      the AWP and supports further research and testing of the instrument.

PMID- 16788258
TI  - Reproducibility of a task description questionnaire for working pregnant women.
AB  - The objective of this study was to evaluate the reproducibility of a Task
      Description Questionnaire that was designed to investigate exposures to, and
      influential factors for, problematic tasks experienced by working pregnant women.
      The questionnaire comprised questions concerning 22 task components (covering
      working posture, manual material handling, work pace, prolonged postures and
      others), eight influential factors contributing to problematic tasks, discomfort
      (measured using a body map) and level of effort to perform the tasks.
      Reproducibility of the questionnaire was assessed by interviewing participants on
      two occasions one week apart for interviews at both 20 and 34 weeks of pregnancy.
      Eleven and 13 problematic tasks were reported by 21 working pregnant women at 20
      and 34 weeks of pregnancy, respectively. These tasks were surveyed using the Task
      Description Questionnaire. Kappa statistics and correlation coefficients
      (supplemented by paired t-tests) were used to examine the reproducibility of
      responses to the questionnaire. The results showed that most of the variables
      were measured with very good or satisfactory reproducibility. The reproducibility
      of exposure to work posture was higher than that of exposure to manual material
      handling. There was no significant difference between test and retest means for
      the discomfort scores measured on the body map, except for the maximum discomfort
      score for the whole body in the 34 weeks survey. The study suggests that the
      questionnaire can be reliably used in the study of problematic tasks experienced
      by pregnant women. But an initial preview of the questions by the subjects and
      explanation of the questions given to the subjects by the interviewer may help to
      produce more reliable results.

PMID- 16788259
TI  - The healthy worker survivor effect in a study of neck muscle performance measures
      in call-centre operators.
AB  - BACKGROUND: The healthy worker survival effect is a complex and poorly controlled
      bias affecting occupational studies. Little is known about its behaviour in
      samples of computer based workers. This descriptive study examined the healthy
      worker effect in relation to muscle performance and neck pain in call-centre
      operators. METHODS: 28 call-centre workers were examined for postural muscle
      performance. Neck pain was measured using a validated questionnaire. Analysis was
      by multivariate regression of the cohort, stratified by years of employment.
      RESULTS: Analysis using the entire sample failed to display any relationship
      between neck pain and muscle performance. Further examination revealed
      survival/secondary selection within the sample, with pain and poor muscle
      performance reduced after 6 years employment. Stratified analysis demonstrated
      that deep flexor muscle performance and posture were statistically significantly
      associated with neck pain. Each stratum explained a greater percentage of the
      variance in questionnaire scores, increasing from 42.3% for the entire sample to
      95.1% for the 4 years employed subgroup. CONCLUSION: The healthy worker survival
      effect is demonstrable in occupations with lower physical demands. It should be
      considered in analysis since it may obscure causal associations. There is no
      single method for controlling this bias and greater understanding of its
      components is required.

PMID- 16788260
TI  - Facilitators and barriers to employment among individuals with psychiatric
      disabilities: a job coach perspective.
AB  - Unemployment rates remain high among individuals with psychiatric disabilities
      despite growing evidence that supported employment programs (SEPs) can help such
      individuals to obtain and retain competitive employment. A complete understanding
      of factors that may facilitate or hinder the success of such supported employment
      efforts is urgently needed to increase the efficacy of SEPs and move more
      individuals with psychiatric disabilities from welfare to work. This exploratory
      study provides insight into potential facilitators and barriers to employment
      among individuals with psychiatric disabilities from the perspective of job
      coaches. Twenty-eight job coaches from 14 SEPs in a Northeastern state reported
      on their experience with four recent clients, two who were successful in
      obtaining employment and two who failed, through a semi-structured mail survey.
      Findings suggest that job coaches use similar strategies to assist clients, but
      in each case try to tailor specific strategies to client's needs and
      characteristics. Factors that influence successful job placement and research and
      policy implications are discussed.

PMID- 16788261
TI  - Comparison of seven measures of sickness absence based on data from three
      counties in Sweden.
AB  - The objective was to compare the applicability of and results provided by the two
      measures of sickness absence used most often within the Swedish social insurance
      administration (that is, unadjusted sick-leave rate and adjusted sick-leave rate)
      and five measures suggested by epidemiological researchers. Data consisted of
      four cross-sectional data sets of registry sick-leave data covering four separate
      years (1997-2000) in three counties. In total 454,000 persons qualified for
      sickness insurance and aged 20-64 years were included. The two measures used
      within the social insurance administration and three of the five measures
      suggested by epidemiological researchers revealed sex-related dissimilarities in
      absence patterns that indicated that women had more sickness absence than men.
      However, in marked contrast to those results, two of the epidemiologically based
      measures (i.e., length of sickness absence and duration of sickness absence)
      instead showed highly comparable rates of sick leave for men and women, and such
      information is seldom obtained, albeit definitely of importance, when trying to
      make a correct assessment of sickness absence. The measure of sickness absence
      that is used influences the findings and should therefore be chosen with care.
      Complementing the measures used in the social insurance administration by five
      measures suggested by epidemiological researchers provided a more informative and
      comprehensive picture of sickness absence in a population. Further investigations
      into the effect of using different measures is needed, as well as international
      consensus on what to call different measures.

PMID- 16788262
TI  - Comparing groups on latent variables: a structural equation modeling approach.
AB  - Structural equation modeling (SEM) provides a dependable framework for testing
      differences among groups on latent variables (constructs, factors). The purpose
      of this article is to illustrate SEM-based testing for group mean differences on
      latent variables. Related procedures of confirmatory factor analysis and testing
      for measurement invariance across compared groups are also presented in the
      context of rehabilitation research.

PMID- 16788263
TI  - Extended dynamical HAADF STEM image simulation using the Bloch-wave method.
AB  - An extended method is proposed for the precise simulation of high-angle annular
      dark-field (HAADF) scanning transmission electron-microscope (STEM) images for
      materials containing elements with large atomic numbers and for thick specimens.
      The approach combines a previously reported method utilizing two kinds of optical
      potential [Watanabe, Yamazaki, Hashimoto & Shiojiri (2001). Phys. Rev. B, 64,
      115432] with a representation of a crystal sliced into multiple layers. The
      validity of the method is demonstrated by simulated images for elements with the
      diamond structure (Si, Ge and alpha-Sn) and for the perovskite BaTiO3.

PMID- 16788264
TI  - Polarization-dependent six-beam X-ray pinhole topographs.
AB  - X-ray six-beam pinhole topograph images were obtained for a silicon crystal with
      incident synchrotron X-rays. The polarization state of X-rays incident on the
      sample crystal was controlled by using a four-quadrant phase-retarder system
      [Okitsu et al. (2002). Acta Cryst. A58, 146-154] that can be rotated around the
      transmitted beam axis to generate arbitrarily polarized X-rays. Quantitative
      agreement was found between the experimental and computer-simulated topograph
      images based on the n-beam Takagi-Taupin dynamical theory under the assumption
      that the polarization state of the incident X-rays was identical with the
      experiment. This result confirmed the validity of the computer algorithm to solve
      the n-beam dynamical theory and the proper operation of the rotating four
      quadrant phase-retarder system simultaneously.

PMID- 16788265
TI  - Reconstruction of a yeast cell from X-ray diffraction data.
AB  - Details are provided of the algorithm used for the reconstruction of yeast cell
      images in the recent demonstration of diffraction microscopy by Shapiro,
      Thibault, Beetz, Elser, Howells, Jacobsen, Kirz, Lima, Miao, Nieman & Sayre
      [Proc. Natl Acad. Sci. USA (2005), 102, 15343-15346]. Two refinements of the
      iterative constraint-based scheme are developed to address the current
      experimental realities of this imaging technique, which include missing central
      data and noise. A constrained power operator is defined whose eigenmodes allow
      the identification of a small number of degrees of freedom in the reconstruction
      that are negligibly constrained as a result of the missing data. To achieve
      reproducibility in the algorithm's output, a special intervention is required for
      these modes. Weak incompatibility of the constraints caused by noise in both
      direct and Fourier space leads to residual phase fluctuations. This problem is
      addressed by supplementing the algorithm with an averaging method. The effect of
      averaging may be interpreted in terms of an effective modulation transfer
      function, as used in optics, to quantify the resolution. The reconstruction
      details are prefaced with simulations of wave propagation through a model yeast
      cell. These show that the yeast cell is a strong-phase-contrast object for the
      conditions in the experiment.

PMID- 16788266
TI  - Calculation of spherical harmonics and Wigner d functions by FFT. Applications to
      fast rotational matching in molecular replacement and implementation into AMoRe.
AB  - The FFT calculation of spherical harmonics, Wigner D matrices and rotation
      function has been extended to all angular variables in the AMoRe molecular
      replacement software. The resulting code avoids singularity issues arising from
      recursive formulas, performs faster and produces results with at least the same
      accuracy as the original code. The new code aims at permitting accurate and more
      rapid computations at high angular resolution of the rotation function of large
      particles. Test calculations on the icosahedral IBDV VP2 subviral particle showed
      that the new code performs on the average 1.5 times faster than the original
      code.

PMID- 16788267
TI  - Crystallographic structural organization of human rhinovirus serotype 16, 14, 3,
      2 and 1A.
AB  - The architecture of the human rhinovirus is shown to be based on a
      crystallographic polyhedron (the ico-dodecahedron) with 60 triangular facets and
      32 vertices at points of a body-centered icosahedral lattice. The ico
      dodecahedron is only slightly different from the T = 3 icosadeltahedron of Caspar
      & Klug [Cold Spring Harbor Symp. Quant. Biol. (1962), 27, 1-24]. The capsid of
      the virion is encapsulated between two ico-dodecahedra in scaling relation by a
      factor tau, the golden number. Clusters with axial symmetry of the coat proteins
      VP1, VP2, VP3 and VP4 are considered (decamers, pentamers, hexamers, trimers and
      tetramers). Their crystallographic enclosing forms obey the same laws as a number
      of axial-symmetric proteins, involving planar and linear crystallographic scaling
      relations and having vertices at points of lattices with an integral metric
      tensor. These properties also occur for the icosahedral cluster of each coat
      protein viewed along the symmetry axes (fivefold, threefold and twofold,
      respectively). The structural organization of the rhinovirus in terms of all
      these enclosing forms is independent of the serotype (16, 14, 3, 2, 1A) and is
      typical for a strongly correlated system, as it depends on one single free
      parameter, taken to be the icosahedral lattice parameter a0, which relates the
      geometry with the real structure (up to small variations).

PMID- 16788268
TI  - The formation of low-dimensional metal trihalide crystals in carbon nanotubes.
AB  - Molecular dynamics computer simulation models are employed to study the direct
      filling of single-walled carbon nanotubes (which vary in diameter) with an
      archetypal metal trihalide, LaCl3. The use of relatively simple potential models
      allows the investigation of details of both the atomistic filling mechanism and
      the thermodynamic factors controlling the formation. The resulting low
      dimensional crystallites are analysed with respect to bulk crystal structures and
      compared to experimental high-resolution transmission-electron-microscopy images
      by simulation of equivalent micrographs from one of the obtained potential
      models, resulting in excellent agreement between the simulated and experimental
      images.

PMID- 16788269
TI  - On qualitative and quantitative analysis in analyser-based imaging.
AB  - Using rigorous wave-optical formalism, a general expression is obtained for the
      image intensity distribution in combined analyser-based/propagation-based phase
      contrast imaging. This expression takes into account partial coherence of the
      wave incident on the object as well as the finite resolution of the detector
      system. Using this general expression, two approaches based on the geometrical
      optics and weak-object approximations are applied to derive simple solutions to
      the inverse problem of reconstruction of the phase and amplitude of the object
      wave. With the help of numerical experiments, the two approaches are compared in
      terms of their validity conditions and are shown to impose certain restrictions
      on the properties of the object wave. In particular, it is shown that violation
      of the validity conditions of the geometrical optics or weak-object
      approximations results in the appearance of strong reconstruction artefacts in
      the transmitted intensity near the edges of the objects. The effect of the
      incident wavefront non-uniformity due to imperfections of the imaging set-up on
      image formation and phase/amplitude reconstruction is also discussed. A solution
      to this problem is proposed in the form of a multi-image phase/amplitude
      reconstruction algorithm based on the geometrical optics approximation. This
      algorithm and an algorithm based on the weak-object approximation are applied to
      simulated and experimental images of fibres.

PMID- 16788270
TI  - Fitting valence charge densities at a crystal surface.
AB  - A procedure is reported for obtaining a much better initial parameterization of
      the charge density than that possible from a neutral atom model. This procedure
      involves the parameterization of a bulk charge density model in terms of simple
      variables such as bond lengths, which can then be transferred to the problem of
      interest, for instance a surface. Parameterization is accomplished through the
      fitting of density functional theory calculations for a variety of crystal
      distortions. The details of the parameterization are discussed for the specific
      case of silicon. This parameterized model can then be applied to surfaces or to
      other problems where an initial higher-order model is needed without the addition
      of any extra fitted parameters. The non-convexity of the charge density problem
      is also discussed.

PMID- 16788274
TI  - Help-seeking in the Norwegian Police Service.
AB  - A traditional view is that police officers possess negative attitudes toward
      seeking professional help. However, few empirical studies have investigated help
      seeking behaviour in police services. This study aimed to investigate help
      seeking behaviour, gender differences, and the relationship to self-reported
      physical and mental health problems in the Norwegian police service. Comparisons
      were made with a sample of the general Norwegian population. A comprehensive
      nationwide questionnaire survey of 3,272 Norwegian police officers at all
      hierarchical levels was conducted; measurements included help-seeking, Subjective
      Health Complaint questionnaire (SHC), the Hospital Anxiety and Depression Scale
      (HADS), Paykel's Suicidal Feelings in the General Population, alcohol and
      medication to cope, self reported health, and sick leave. Female police officers
      contacted nearly all health professionals more than their male counterparts. Help
      seeking was largely unaffected by age. Less than 10% of those reporting anxiety
      or depressive symptoms or serious suicidal ideation had contacted a psychologist
      or psychiatrist. A chiropractor had been contacted by 14.5% of the sample during
      the past year, compared with 7% in the general Norwegian population. Anxiety
      symptoms were associated with seeking a chiropractor (OR 1.9, 95% CI 1.3-2.7).
      The strongest association with contacting a psychologist or psychiatrist was
      medication used to cope (OR 5.8, 95% CI 3.0-11.1). The first nationwide study on
      help-seeking behaviour showed that police officers sought help among specialists
      in private practice, physiotherapists and chiropractors relatively often.
      However, they contacted a psychologist or psychiatrist rarely, even when
      reporting serious suicidal ideation.

PMID- 16788275
TI  - Developmental toxicity induced by inhalation exposure of pregnant rats to N,N
      dimethylacetamide.
AB  - Developmental toxicity of N,N-dimethylacetamide (DMAC) was examined by exposing
      pregnant rats by inhalation to DMAC vapor at 0 (control), 100, 300, 450 or 600
      ppm (v/v) for 6 h/d during Gestation Days 6 through 19. Fetal body weight and the
      number of male live fetuses were significantly decreased, along with a tendency
      of the number of intrauterine deaths to increase. The number of fetuses with
      visceral and skeletal malformations was significantly increased in the 450 and
      600 ppm groups, while the number of fetuses with anasarca as an external
      malformation was increased at 600 ppm. Observed cardiovascular malformations
      included ventricular septum defect, persistent truncus arteriosus, malpositioned
      subclavian branch and retroesophageal subclavian artery. Persistent truncus
      arteriosus was accompanied by ventricular septal defect (VSD). Incidences of the
      persistent truncus arteriosus, which was classified as a serious congenital heart
      disease affecting postnatal survival, were increased at 450 and 600 ppm.
      Increased liver weights and hepatocellular swelling occurred in the dams exposed
      to 300 ppm and above, whereas neither hepatocellular necrosis nor increased serum
      activity of liver transaminases was observed in any of the exposed groups.
      Maternal body weights were decreased at 450 and 600 ppm. The most sensitive signs
      of developmental toxicity appeared at the exposure level of 300 ppm which was
      also the level of slight maternal toxicity. The No-Observed-Adverse-Effect-Level
      (NOAEL) was determined as 100 ppm for the endpoints of fetal and maternal
      toxicities. The NOAEL of 100 ppm and the induction of serious cardiovascular
      malformations occurring at 450 ppm and above were discussed with reference to the
      existing occupational exposure limit for DMAC.

PMID- 16788276
TI  - Application of aldehyde dehydrogenase 2 (ALDH2) genetic diagnosis in support of
      decreasing alcohol intake.
AB  - Encouraging behavioral changes to decrease alcohol intake is not easy from the
      standpoint of health support. This study was conducted to examine whether the
      genetic diagnosis of ALDH2 polymorphism is useful in supporting those who want to
      decrease their alcohol intake. The participants in this study were 329 male
      employees who wanted to know the result of their ALDH2 genotype. We divided the
      329 participants randomly into two groups. One was the "notified group" (n=157),
      and the other was the "non-notified group" (n=172). The subjects belonging to the
      "notified group" were informed of the results of the ALDH2 genotype diagnosis in
      April, 2003. Drinking habits and laboratory data were obtained before and after
      notification of the ALDH2 genotype. Among those with genotype ALDH2*1/*1, there
      was no significant change in drinking frequencies, nor was there any significant
      decline in liver function laboratory data in either of the groups before and
      after notification of the genotype. However, weekly alcohol intake tended to
      increase compared to that before notification. On the other hand, with regard to
      those with genotype ALDH2*1/*2, no significant changes in drinking frequencies or
      liver function laboratory data were evident in either group before and after
      notification of the genotype. However, the weekly alcohol intake tended to
      increase in the non-notified group, whereas it tended to decrease in the notified
      group. Although the result was not significant, it is suggested that, with
      further study and an increased sample size, the genetic diagnosis may be found to
      be useful.

PMID- 16788277
TI  - Health status of workers in small and medium-sized companies as compared to large
      companies in Japan.
AB  - The health status of workers in small companies has been noted to be relatively
      poor, but no actual comparisons of groups of variously sized companies within the
      same region based on the same methodology have ever been conducted. We undertook
      this study to clarify differences in health status according to company size. The
      subjects comprised workers of a Japanese steel company and various subcontractors
      who received health checkups in 2003. We obtained answers from 83 companies
      employing 11,844 workers and analyzed the data for 6,480 men aged 40 yr or more,
      comparing results of the health checkups, health management practices, and number
      of occupational health personnel according to company size (number of employees).
      Mean worker age in the various groups ranged from 49.7 to 54.0 yr. Drinking and
      smoking habits did not differ between them. There was a significant trend to
      higher prevalences of diabetes and hypertension, and lower prevalences of renal
      disease and hypercholesterolemia in smaller companies. Mean body mass index and
      diastolic blood pressure were significantly higher in companies with 1,000-2,999
      workers. Health management practices satisfied the legal requirements of the
      respective company size. Occupational physicians devoted more time per worker in
      companies with 1,000-2,999 and 50-299 workers. No consistent differences were
      apparent between small and large companies in worker health status. Inter-company
      activities for occupational safety and health were undertaken and labor
      regulations almost equally adhered to. Endeavors to maintain a certain level of
      hygiene and health management play an important role in maintaining worker health
      in small companies.

PMID- 16788278
TI  - Effectiveness of a low-intensity intra-worksite intervention on smoking cessation
      in Japanese employees: a three-year intervention trial.
AB  - To test the effectiveness of a low-intensity intervention program for smoking
      cessation targeting the worksite environment in employees who had a low readiness
      to quit, we conducted an intervention trial at six intervention and six control
      worksites in Japan. A total of 2,307 smokers at baseline who remained at their
      worksite throughout the three-year study period were analyzed (1,017 in
      intervention and 1,290 in control groups). The multi-component program at the
      worksites consisted of (1) presenting information on the harms of tobacco smoking
      and the benefits of cessation by posters, websites, and newsletters; (2) smoking
      cessation campaigns for smokers; (3) advice on designation of smoking areas; and
      (4) periodic site-visits of the designated smoking areas by an expert researcher.
      At baseline, the intervention and control groups each had high prevalence of
      immotive or precontemplation, that reflected low readiness to quit (71.5% and
      73.2%, respectively). The smoking cessation rate, as not having smoked for the
      preceding six months or longer, assessed at 36 months after the baseline survey
      by a self-administered questionnaire was significantly higher in the intervention
      group than the control group (12.1%, vs. 9.4%, p=0.021). The intervention program
      still had a significant effect on the smoking cessation rate after multiple
      logistic regression analysis adjusted for sex, age, type of occupation, age of
      starting smoking, quit attempts in the past, number of cigarettes per day, and
      readiness to quit (odds ratio: 1.38, 95% confidence interval: 1.05-1.81, p=0.02).
      The cost per additional quitter due to the intervention was calculated to be Yen
      70,080. These findings indicate that this program is effective and can be
      implemented in similar workplaces where the prevalence of smoking is high and
      smokers' readiness to cease smoking is low.

PMID- 16788279
TI  - Work and family life of childrearing women workers in Japan: comparison of non
      regular employees with short working hours, non-regular employees with long
      working hours, and regular employees.
AB  - This study assessed the working and family life characteristics, and the degree
      of domestic and work strain of female workers with different employment statuses
      and weekly working hours who are rearing children. Participants were the mothers
      of preschoolers in a large Japanese city. We classified the women into three
      groups according to the hours they worked and their employment conditions. The
      three groups were: non-regular employees working less than 30 h a week (n=136);
      non-regular employees working 30 h or more per week (n=141); and regular
      employees working 30 h or more a week (n=184). We compared among the groups the
      subjective values of work, financial difficulties, childcare and housework
      burdens, psychological effects, and strains such as work and family strain, work
      family conflict, and work dissatisfaction. Regular employees were more likely to
      report job pressures and inflexible work schedules and to experience more strain
      related to work and family than non-regular employees. Non-regular employees were
      more likely to be facing financial difficulties. In particular, non-regular
      employees working longer hours tended to encounter socioeconomic difficulties and
      often lacked support from family and friends. Female workers with children may
      have different social backgrounds and different stressors according to their
      working hours and work status.

PMID- 16788280
TI  - Work characteristics and upper extremity disorders in female dental health
      workers.
AB  - Many dental health workers suffer from musculoskeletal disorders in the upper
      extremities. In addition to ergonomic factors, psychosocial work characteristics
      have been linked to musculoskeletal disorders. The present cross-sectional study
      aimed at investigating how musculoskeletal disorders in the upper extremities
      (UED) and occupational position are related to work characteristics and general
      health problems in female dental health workers. Questionnaire data from
      dentists, dental hygienists and dental nurses (N=945) showed that 81% reported
      UED. Multivariate analysis of variance showed that dentists reported the highest
      levels of physical load and fatigue whereas dental nurses reported the lowest
      levels of influence at work. Irrespective of position, those with UED considered
      their physical and psychosocial work environment and their own health to be
      significantly poorer than did those without UED. A hierarchical multiple
      regression showed that the physical load of dentistry was most strongly related
      to UED. Despite improvements to the ergonomics and physical work environment of
      dentistry, it is concluded that female dental health workers are still at high
      risk of developing UED.

PMID- 16788281
TI  - An inverse association between serum gamma glutamyl transpeptidase activity and
      Breslow's Lifestyle Index; its practical application for screening of subjects
      with unhealthy lifestyles.
AB  - We examined whether serum gammaGTP activity (gammaGTP) is associated with
      Breslow's lifestyle index and whether it could be used as a tool to detect
      subjects with unhealthy lifestyles. To that effect, 724 male Japanese workers
      excluding patients suffering from hepatitis virus infection, autoimmune liver
      diseases and apparently active bile duct diseases were cross-sectionally
      examined. gammaGTP was inversely associated with the total score of Breslow's
      index for all subjects (lambda=30.643) and in subjects aged 40 or more
      (lambda=37.073). The association was consistent even after adjustments of
      subjects' ages and levels of triglycerides, total cholesterol and uric acid
      (p=0.0001). Among the seven lifestyle factors comprising Breslow's index,
      improper habits of drinking (p<0.0001), smoking (p=0.0204), exercise (p=0.0189)
      and body weight control (p<0.0001), were associated with increased gammaGTP. Even
      in a survey in which subjects who had proper habits of drinking and body weight
      control were selectively examined, improper habits of smoking and exercise still
      tended to be associated with increased gammaGTP. Receiver operating
      characteristic curves indicated that gammaGTP was beneficial for detecting
      subjects who scored two or less on Breslow's index, at least in subjects aged 40
      or more. gammaGTP was associated with insulin resistance level estimated by the
      homeostasis model assessment (p<0.0001), which was inversely associated with
      Breslow's index (p=0.0040). gammaGTP could be used as an objective substitute of
      Breslow's index, allowing us to identify subjects with low scores on Breslow's
      index, at least after sorting subjects properly. Such screening would enable
      interventions to correct subjects' unhealthy lifestyles, helping to solve
      lifestyle-related disease issues.

PMID- 16788282
TI  - Performance of a fume-exhaust gun system in CO2 arc welding.

PMID- 16788283
TI  - Plasma catecholamine levels and neurobehavioral problems in Indian firefighters.
AB  - Firefighting is a stressful and hazardous job. Persons engaged in firefighting
      are highly exposed to work-related stress as well as to smoke containing a host
      of chemicals potentially harmful to human health. In order to elucidate whether
      firefighting affects neuroendocrine and behavioral responses of firefighters,
      plasma catecholamine (CA) levels and the prevalence of neurobehavioral symptoms
      in 62 firefighters (all males, mean age 43 yr) and 52 control subjects matched
      for age and sex were examined in this study. Self-reported neurobehavioral
      symptoms data were obtained from a questionnaire survey and personal interview.
      Concentrations of epinephrine (E), norepinephrine (NE) and dopamine (DA) in
      plasma were measured by high-performance liquid chromatography with
      electrochemical detection. Compared with matched controls, the firefighters
      showed higher prevalence (p<0.05) of neurobehavioral symptoms such as burning
      sensation in the extremities, tingling and numbness, transient loss of memory,
      and depression, but no significant difference was recorded in the prevalences of
      anxiety, vertigo and dizziness. The firefighters demonstrated a more than two
      fold (p<0.05) rise in plasma levels of E and NE, but the plasma DA level was
      relatively unchanged. Controlling age and smoking as possible confounders,
      firefighting was found to be associated with raised E (OR=2.15; 95% CI, 0.98
      4.52), and NE levels (OR=2.24 95% CI, 1.22-3.61). In conclusion, the job of
      firefighting appears to be associated with stimulation of sympathetic activity
      and a rise in the prevalence of neurobehavioral symptoms.

PMID- 16788284
TI  - Factors related to the prevalence of respiratory symptoms in workers in a
      petrochemical complex.
AB  - This study was performed to evaluate the prevalence of respiratory symptoms in
      workers in a petrochemical complex and to elucidate the relationship between the
      prevalence and work-related factors. A questionnaire was distributed to 5,983
      male workers working in a petrochemical complex. As for the respiratory symptoms,
      cough was present in 2.4%, phlegm in 8.1%, wheezing in 2.8% and shortness of
      breath in 4.7% of the workers. The factors significantly related to respiratory
      symptoms were smoking history, wearing of protective devices, handling of
      substances toxic to the respiratory system, and history of atopy or respiratory
      disease (p<0.05). The substances toxic to the respiratory system were divided
      into 4 types, ie., dusts, solvents, metals, and vapors. When the analysis was
      performed to evaluate the effects of exposure to substance type on respiratory
      symptoms, the odds ratio of cough was 1.96 times higher in those workers exposed
      to dusts compared with those not exposed, 2.28 times for exposure to metals, 1.52
      times for solvents, and 1.55 times for vapors, all showing significant
      differences (p<0.05). For phlegm, the odds ratio was 1.08 times higher in those
      workers exposed to dusts compared with those not exposed, 1.94 times for exposure
      to metals, 1.70 times for organic solvents, and 1.85 for vapors (p<0.05). For
      wheezing, the odds ratio was 2.38 times for exposure to dusts; for shortness of
      breath, it was 2.42 times for exposure to dusts, 2.89 times for metals, 2.10
      times for organic solvents, and 2.14 times for vapors, all showing significant
      differences (p<0.05). In conclusion, work-related factors significantly affected
      the respiratory symptoms in workers working in the petrochemical complex.
      Especially, these respiratory symptoms were significantly related to exposure to
      toxic substances and the wearing of protective devices. Thus, safety education
      and management are needed for these workers.

PMID- 16788285
TI  - [Elucidation of the energy absorption spectra of the (11)C beam in a plastic
      scintillator.].
AB  - Heavy ion therapy using the energetic (12)C beam is successfully under way at
      HIMAC, Japan. The method is more advantageous than traditional radiation therapy
      in dose concentration owing to the Bragg peak and high relative biological
      effectiveness. A research study using the (11)C beam for heavy ion therapy in the
      future has been carried out in order to develop the capability of monitoring the
      dose distribution. Our group has examined the total energy absorption spectrum of
      the (11)C beam in a plastic scintillator. We could clearly observe the total
      absorption peak of (11)C in the energy spectrum and, in addition, we found a
      broad bump structure was associated with the peak. The bump area occupies 37% of
      the total spectrum and it probably affects the dose calculation for an accurate
      treatment planning. We elucidated the mechanism that leads to the structure of
      the total energy absorption spectra given by (11)C and (12)C in a block of
      plastic scintillator. This paper describes the method in detail and gives
      experimental analysis results which deal with the bump structure. We could
      explain the bump structure using the energy spectra caused by the fragmentation
      reactions.

PMID- 16788286
TI  - Resonance of sputum spigot with air vibration.
AB  - A mathematical model calculation has been presented on the resonant frequency of
      the oscillating sputum spigot in a cylindrical pipe, with which we investigated
      similar phenomena in bronchial tubes. We confirmed the theoretical results by two
      types of experiments using pseudo-sputum (5 and 10% solutions of mucin) spigots
      instead of a human pulmonary one, and found the model was suitable for estimating
      the effects of clinical vibrational treatments expectorating sputum spigots
      plugged in small bronchi. The main points of the paper are summarized as follows.
      1. The validity of the fluid model used was verified using reported experimental
      data of Litt and co-workers. After adjusting their data in a Casson plot, Casson
      fluidity was found to be the best parameter to represent viscosity of the sputum.
      2. A theoretical investigation on the vibrational sputum spigots in narrow tubes
      was done using an analytical model calculation. From the resultant formula, which
      expresses the resonant frequency of the oscillation of the spigot with its
      physical values (the radius of the airway, the length of the spigot, the
      elasticity of the sputum, and the surface tension), many points became clear; for
      example, the resonant frequency of sputum spigot vibration in a narrow bronchial
      tube is too high to propagate there under the effective influence of surface
      tension. 3. Two experiments were performed with pseudo-sputum (5 and 10%
      solutions of mucin) instead of a human pulmonary one. After substituting the
      resonant frequencies of the pseudo-sputum spigot vibration in our tube experiment
      into the resultant formula derived from our analytical model calculation we
      estimated the elasticity values, which agreed with those from our plate
      experiment. The validity of our theory was strongly supported by this agreement.

PMID- 16788288
TI  - [Measurement of the air kerma using dosimeters embedded in an acrylic phantom in
      interventional radiology.].
AB  - Interventional radiology procedure guidelines and a measurement manual (IVR
      guidelines) have been published for the maintenance of interventional equipment
      with an objective of avoiding serious radiation-induced skin injuries. In the IVR
      guidelines, the positioning of a dosimeter at the interventional reference point
      is determined, whereas placement of a phantom is not specified. Therefore, the
      phantom is placed at any convenient location between the dosimeter and image
      intensifier. The space around the dosimeter reduces detection of scattered
      radiation. In this study, dosimeters (consisting of a parallel plate ionization
      chamber, glass dosimeter and OSL dosimeter) were embedded in the phantom surface
      to detected scattered radiation accurately. As a result, when dosimeters were
      embedded in the phantom surface, the air kerma was increased compared with that
      when dosimeters were placed on the phantom. This suggested that embedded
      dosimeters were able to detect scattered radiation from the phantom.

PMID- 16788287
TI  - Dosimetric properties of the liquid ionization chamber electronic portal imaging
      device (EPID).
AB  - In the relation between the pixel values of the electronic portal imaging device
      (EPID) and dose rate, pixel values have been reported to be proportional to the
      square roots of the dose rates although some researchers have reported that each
      EPID pixel value was almost proportional to the dose rates when they were more
      than 1 Gy/min. To resolve this contradiction, in this study we have investigated
      the dosimetric properties of the liquid ionization chamber EPID based on a two
      dimensional matrix of liquid- filled ionization chambers. Our results show that
      the pixel values of this EPID were proportional to the square roots of the dose
      rates when they were less than 0.5 Gy/min, and the values were proportional to
      the dose rates when they were more than that. In addition, the survival time of
      electrons in the liquid of the EPID is reportedly dependent on the amount of
      impurities in the liquid ionizing chamber of EPID. The pixel values of the EPID
      acquired in rapid succession, increased. In the results, the pixel values were
      constantly increased to approximately 0.2% of pre-images for less than 15 s of
      the rest interval. When changes in the sensitivity of each pixel value were
      approximately 1%, approximately 5% changes were observed against the transformed
      dose rate. To avoid this difference, we developed the following formula relating
      the pixel value, P, and dose rate, D. P=a D + b radicalD - k h (a, b, h:
      constants, k : variable).

PMID- 16788289
TI  - Colonoscopy demand and practice in a regional hospital over 9 years in Hong Kong:
      resource implication for cancer screening.
AB  - BACKGROUND: The incidence of colorectal cancer (CRC) in Hong Kong is rising. The
      trend of colonoscopy demand is uncertain. AIM: To investigate colonoscopy demand
      and practice in a Hong Kong regional hospital over the past nine years. METHODS:
      Colonoscopy data from 1st January 1997 to 31st August 2005 were retrieved and
      divided into two equal periods for comparison. Colonoscopy practice and findings
      between the two periods were compared. RESULTS: There was no change in the number
      of endoscopists and colonoscopy sessions in the two periods. The number of
      colonoscopy done in the two periods was 2,681 and 2,871, respectively. The
      indications for screening of CRC/polyp (9.3 vs. 24.7%, p < 0.0001) and
      surveillance of CRC/polyp (4.7 vs. 10.9%, p < 0.0001) were increased, but
      decreased for diarrhea (18 vs. 10.2%, p < 0.0001) and per rectal bleeding (19 vs.
      8.1%, p < 0.0001). The waiting time was lengthened from 2 to 4 weeks (p <
      0.0001). The percentage of colonic adenomas (19.9 vs. 27.2%, p < 0.0001) was
      increased. A right-shift was observed in both CRC (37 vs. 50%, p = 0.018) and
      adenoma (21.6 vs. 38.1%, p < 0.0001). CONCLUSION: The number of colonoscopies
      performed was governed by capacity partly through lengthening of waiting time to
      cope with demand. Ways to improve capacity for colonoscopies is needed.

PMID- 16788291
TI  - Food hypersensitivity reactions visualised by ultrasonography and magnetic
      resonance imaging in a patient lacking systemic food-specific IgE.
AB  - BACKGROUND: Abdominal complaints related to food intake might be due to
      hypersensitivity. A firm diagnosis of food allergy is often difficult to
      establish, particularly in the absence of systemic food-specific IgE. Using
      ultrasonography and magnetic resonance imaging (MRI) we were able to visualise
      the intestinal response in one such case. METHODS: A 24-year-old female presented
      with self-reported food hypersensitivity, particularly related to the intake of
      egg. Nausea and diarrhoea were predominant symptoms. Double-blind placebo
      controlled food challenge with raw egg was positive, but all other conventional
      tests of food hypersensitivity, including skin prick test, total and food
      specific IgE in serum, were negative. A thorough investigation programme could
      not reveal any organic disease of the gastrointestinal tract. We extended the
      evaluation to include two new provocation tests, where intestinal wall thickening
      and the amount of luminal liquid were monitored by external abdominal ultrasound
      and MRI. RESULTS: Both ultrasound and MRI investigations indicated intestinal
      wall thickening and influx of large amounts of fluid into the proximal small
      intestines within 10 min of duodenal challenge with egg. The response was
      associated with abdominal pain and bloating. CONCLUSIONS: The response to
      provocation was typical of an immediate allergic reaction. Our results indicate
      that local food-induced hypersensitivity reactions can occur in the gut in the
      absence of systemic indications of IgE-mediated allergy. Abdominal
      ultrasonography and MRI might become valuable tools for documenting such
      responses.

PMID- 16788290
TI  - Gene expression profiles on hypoxia and reoxygenation in rat gastric epithelial
      cells: a high-density DNA microarray analysis.
AB  - Previous investigations have demonstrated that the cellular signaling induced by
      hypoxia-reoxygenation is a major pathway contributing to gastric mucosal injury
      induced by stress, non-steroidal anti-inflammatory drugs, and Helicobacter
      pylori. The aim of the present study was to perform a gene expression analysis of
      the gastric mucosal cellular response and to define the protective molecules in
      hypoxia and reoxygenation using a high-density DNA microarray analysis. Normal
      rat gastric mucosal (RGM-1) cells were subjected to hypoxia for 2 h, and
      reoxygenation was initiated by placing the cells in an environment of normoxia
      for 2, 4, or 8 h. Total RNA was extracted, and differences in the gene expression
      profiles between the normoxia and hypoxia groups or among the different durations
      of reoxygenation were investigated using a high-density DNA microarray. HIF-1-
      and apoptosis-related genes were modulated by hypoxia. Moreover, inflammation-,
      stress-, and wound- healing-related genes were regulated by reoxygenation
      following hypoxia. In particular, the expression of heat shock protein-70,
      amphiregulin and cyclooxygenase-2 were upregulated during reoxygenation following
      hypoxia, suggesting that these upregulations may play an important role in
      maintaining cell survival and supporting cell function.

PMID- 16788292
TI  - Immunology of Helicobacter pylori infection.
AB  - Helicobacter pylori is a Gram-negative, spiral bacterium that colonizes the
      gastric mucosa of at least 50% of the world's population and plays a causative
      role in the development of chronic gastritis as well as in gastric and duodenal
      ulcers. H. pylori triggers vigorous humoral and cellular immune responses in both
      systemic and mucosal compartments. In spite of this response, the vast majority
      of infected hosts are unable to clear the infection, and it persists for decades.
      Although Helicobacter is tolerated by a naive host organism, preclinical studies
      have demonstrated that prophylactic or therapeutic vaccinations efficiently clear
      Helicobacter from the stomach. The understanding of the mechanisms leading to the
      Helicobacter persistence or the vaccine-induced eradication of Helicobacter in
      animal models will help to define optimal immunization strategies for future anti
      Helicobacter vaccination clinical trials.

PMID- 16788293
TI  - The fetal variant of the circle of Willis and its influence on the cerebral
      collateral circulation.
AB  - In a fetal-type posterior circle of Willis (FTP) there is an embryonic derivation
      of the posterior cerebral artery (PCA) from the internal carotid artery (ICA).
      Besides the fact that a larger area is thus dependent on the ICA, leptomeningeal
      vessels cannot develop between the anterior and posterior circulation. The
      tentorium namely prevents cerebellar vessels from connecting to the PCA
      territory. Therefore patients with an FTP could be more prone to develop vascular
      insufficiency. An overview of the literature is given. We propose to define a
      partial FTP, in which a small P1 segment between the basilar artery and the
      postcommunicating part of the PCA is present, and a full FTP, in which the P1
      segment is absent. Whether a full FTP is a risk factor for stroke should be
      subject of further investigation.

PMID- 16788294
TI  - High titer of anticardiolipin antibody is associated with first-ever ischemic
      stroke in Taiwan.
AB  - BACKGROUND AND PURPOSE: The association between anticardiolipin antibody (aCL)
      and ischemic stroke is controversial, and there are few case-control studies of
      Asian populations. The aim of this study, therefore, was to determine whether aCL
      is an independent risk factor for ischemic stroke in Taiwanese patients over the
      age of 40 years. METHODS: Both the IgG and IgM isotypes of aCL were measured in
      273 patients (> 40 years of age) hospitalized for first-ever ischemic stroke and
      in 181 non-stroke controls. Results were defined as: negative (< 10 IgG
      phospholipid units [GPL] or < 7.5 IgM phospholipid units [MPL]); low positive (10
      20 GPL or 7.5-15 MPL); or, high positive (> 20 GPL or > 15 MPL). Odds ratios (OR)
      were estimated by logistic regression with adjustment for potential confounders.
      RESULTS: A high positive IgG aCL was present in 4.4% of the stroke patients and
      1.2% of the controls. Age- and sex-adjusted analysis showed a borderline
      association between a high positive level for aCL IgG titer and stroke, with an
      OR of 4.01 (95% CI 0.87-18.37; p = 0.0739). Final analysis, with adjustments for
      age, sex, hypertension, diabetes, tobacco smoking, atrial fibrillation, left
      ventricular hypertrophy and hyperlipidemia, revealed an OR of 5.25 (95% CI 1.06
      25.89; p = 0.0419). CONCLUSIONS: The results of this study suggest that elevated
      titer of aCL IgG (> 20 GPL) is associated with first-ever ischemic stroke in
      Taiwanese patients aged over 40 years. High positive aCL titer is related to
      ischemic stroke after adjustment for conventional cerebrovascular risk factors,
      indicating that it is probably an independent risk factor for ischemic stroke.

PMID- 16788295
TI  - Activity Index - a complementary ADL scale to the Barthel Index in the acute
      stage in patients with severe stroke.
AB  - OBJECTIVE: It was the aim of this study to compare the Barthel Index (BI) and the
      activities of daily living (ADL) component of the Activity Index [AI(ADL)]
      regarding floor and ceiling effects, responsiveness and the predictive value for
      survival during the first week until 3 months after stroke onset. PATIENTS AND
      METHODS: Basic ADL were assessed in 75 patients with ischaemic stroke. RESULTS:
      There was a strong concordance between BI and AI(ADL) scores at all time points
      (Kendall's taub = 0.7878, p < 0.0001 at baseline; Kendall's taub = 0.8901, p <
      0.0001 at 1 week; Kendall's taub = 0.9027, p < 0.0001 at 3 months). BI had a
      significantly more pronounced floor effect at baseline and at 1 week compared
      with AI(ADL) in patients with severe stroke. Both scales had a substantial
      ceiling effect at 3 months. At 1 week, the baseline BI score was significantly
      higher in patients being alive as compared with those who had died, while their
      AI(ADL) score did not differ significantly. At 3 months, baseline BI and AI(ADL)
      scores were significantly higher in patients being alive as compared with those
      who had died. The predictive value of being alive at 1 week and 3 months did not
      differ between BI and AI(ADL). CONCLUSION: AI(ADL) is recommended to be used in
      addition as a complement to BI in patients with severe stroke since the floor
      effect with BI in the acute stage is significantly more pronounced than with
      AI(ADL), thus hampering the responsiveness.

PMID- 16788296
TI  - Predictive implications of recurrent transient ischemic attacks in large-artery
      atherosclerosis.
AB  - BACKGROUND: It is uncertain whether recurrent transient ischemic attacks (R
      TIAs), when comparing with single TIAs (S-TIAs), have any distinct mechanisms.
      METHODS: All consecutive patients with TIAs, who had been admitted for a 2-year
      period, were divided into two groups: those who had R-TIAs and those who had S
      TIAs. Registry data, medical records, and imaging findings were reviewed and
      compared between the two groups. RESULTS: There were 85 patients who had TIAs: 42
      patients had R-TIAs, and 43 patients had S-TIAs. On univariate analysis, R-TIA
      patients had less cardiac embolic TIA sources, less weakness, less speech
      disturbances, shorter symptom duration, a longer time interval from onset to
      treatment, less abnormalities on diffusion-weighted magnetic resonance imaging,
      and more significant relevant arterial stenoses. After logistic regression
      analysis, independent factors associated with R-TIAs were symptom duration < 10
      min (odds ratio OR 3.62; 95% confidence interval CI 1.37-9.57), > or = 50%
      stenosis of the clinically relevant artery (OR 7.08; 95% CI 1.29-38.71), and
      absence of cardiac embolic sources (OR 0.04; 95% CI 0.002-0.71). CONCLUSIONS: R
      TIAs may have pathophysiological mechanisms distinct from those of S-TIAs and so
      may provide a clue for the etiologic diagnosis, in that patients with R-TIAs are
      more likely to have large-artery atherosclerosis.

PMID- 16788297
TI  - Deep vein thrombosis following ischemic stroke among Asians.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is perceived as uncommon among Asian
      stroke patients. However, there is a paucity of published data, and thus, we
      studied the frequency, characteristics and prognosis of DVT following ischemic
      stroke in Asian patients with lower limb paresis. METHODS: Doppler ultrasound
      scans of the lower limbs were performed at days 7-10 and 25-30 after stroke
      onset. The functional status of patients was assessed at 6 months using the
      modified Rankin scale. RESULTS: DVT was detected in 30% of patients at days 7-10
      and in 45% of patients at days 25-30. Most thromboses were distal. There were
      significant associations of age and degree of weakness with the presence of DVT
      at days 25-30, but not at days 7-10. DVT in the first month after stroke was
      associated with poorer outcome at 6 months. CONCLUSIONS: DVT following ischemic
      stroke among Asians is common and associated with poor functional outcome.

PMID- 16788298
TI  - Effect of social deprivation on mortality and the duration of hospital stay after
      a stroke.
AB  - BACKGROUND: We aim to assess whether social deprivation independently predicts
      case fatality after a stroke patient has been admitted to hospital, and to assess
      whether social deprivation affected duration of hospital stay. METHODS: Cohort
      study in a tertiary teaching hospital included consecutive patients admitted to
      hospital within 48 h of their stroke between 1988 and 1994. Outcome measures were
      case fatality at 1 year and length of hospital stay. The socioeconomic category
      was derived from the postcode sector of residence for the patients (Carstairs
      index). Cause of death was determined by data linkage to the Registrar General
      data for Scotland. RESULTS: 2,042 stroke patients were included. A significant
      age difference existed between the deprivation categories (76.0 +/- 10.9 years in
      the affluent cohort vs. 71.4 +/- 10.7 years in the deprived cohort). Smoking was
      more common in the deprived group. ECG findings and neurological score on
      admission were similar between the groups. No difference existed between groups
      for length of hospital stay (p = 0.793), and in the proportions remaining alive
      at 1 year (p = 0.416). When entered into a multivariate Cox regression analysis,
      the deprivation categories did not predict mortality. Age, sex, Philadelphia
      Geriatric Center Instrumental Activities of Daily Living (IADL) Scale Score,
      Orgogozo neurological score on admission, and ECG abnormalities were the
      significant predictors. CONCLUSIONS: Stroke patients living in more socially
      deprived areas had their strokes at an earlier age but were not at a greater risk
      of dying or longer hospital stay once they had been admitted to hospital.

PMID- 16788299
TI  - Dose titration to reduce dipyridamole-related headache.
AB  - BACKGROUND: Combination of low-dose aspirin and modified-release dipyridamole
      (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over
      aspirin alone. However, headaches were reported in more patients receiving
      dipyridamole-containing agents than in those receiving placebo. We undertook a
      randomized, double-blind, placebo-controlled trial to evaluate which dosing
      regimens of ASA+MR-DP have better tolerance. METHODS: This trial randomized 146
      patients with a history of ischemic cerebrovascular disease into three groups:
      placebo (days 1-28), reduced dose (placebo on days 1-4, ASA+MR-DP once daily
      before bed during days 5-14, and b.i.d. on days 15-28), and regular dose (placebo
      on days 1-4, and ASA+MR-DP b.i.d. on days 5-28). Using Chinese diary card,
      headache was assessed as mean cumulated headache (Sigma frequency x
      intensity/occurrence days x study days) over the study period, and was graded 0-4
      according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version
      2.0. RESULTS: Intent-to-treat patients after randomization was 46 in placebo
      group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse
      effects, headache of any grade occurred significantly more in the regular dose
      group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated
      headache was higher (p < 0.05) in the regular dose group than in the reduced
      group during days 5-14. Of 27 patients who dropped out, 15 (55.6%) were due to
      headache, which was substantially more in regular dose (8, 53.3%), though the
      difference was statistically insignificant. CONCLUSIONS: Initial reduced dose
      treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems
      better tolerated by those susceptible to phosphodiesterase inhibitor-induced
      headache.

PMID- 16788300
TI  - Stroke risk of asymptomatic intra- and extracranial large-artery disease in
      apparently healthy adults.
AB  - BACKGROUND: The predictive value of asymptomatic intracranial artery stenosis for
      future stroke remains uncertain. The aim of this study is to assess the stroke
      risk of asymptomatic intracranial artery stenosis and to compare it with that of
      extracranial artery disease. METHODS: The study subjects were 2,924 participants
      (mean age 55 years) without any history of stroke. We examined the relation
      between intra- or extracranial large-artery disease and subsequent
      cerebrovascular events (mean follow-up 63 months). RESULTS: The incidence rate of
      total cerebrovascular events in persons with intracranial artery stenosis was
      1.3% per year. In the group without plaque in the extracranial carotid arteries,
      the annual rate of total cerebrovascular events was only 0.6%, but in the group
      with plaque, the rate was 3.6%. Kaplan-Meier analysis of total events showed a
      significant difference between the 2 groups (p = 0.002). CONCLUSIONS: The stroke
      risk in subjects with asymptomatic extracranial artery disease is markedly
      increased if intracranial artery stenosis is also present.

PMID- 16788301
TI  - Intracerebral hemorrhage: outcomes and eligibility for factor VIIa treatment in a
      National Stroke Registry.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating form of stroke for
      which the lack of treatment options, high mortality rate, and the tendency to
      severely disable result in high social and economic burden. METHODS: We analyzed
      data in the Registry of the Canadian Stroke Network (RCSN). We sought to: (1)
      provide a descriptive analysis of ICH; (2) determine the proportion of ICH
      patients that might have been eligible for treatment with recombinant activated
      factor VII (rFVIIa) using criteria from a recent phase II trial; (3) compare 6
      month outcomes of ICH patients with those of ischemic stroke patients, matched
      for gender, age, and stroke severity. RESULTS: In the RCSN, 11% of all strokes
      were nontraumatic ICH. The median Canadian Neurological Scale score was 7. A
      minority (33%) of patients arrived to the emergency department in less than 3 h
      from onset. In this cohort, in-hospital mortality was 15%. At 6 months, a further
      9% of patients had died and 58% had a slight to no disability (Stroke Impact
      Scale-16 score > or = 75). Approximately 20% of ICH patients would have been
      eligible for rFVIIa treatment. Compared to ischemic stroke, ICH showed a trend
      towards increased mortality at discharge (OR: 1.96, CI: 0.99-3.87). At 6-month
      follow-up, ICH showed increased mortality (OR: 2.27, CI: 1.29-3.97), yet
      functional outcomes were not significantly different. CONCLUSION: ICH patients
      had a higher case-fatality rate when compared to acute ischemic stroke, but
      survivors had similar functional outcomes. In Canada, about one fifth of ICH
      patients might potentially benefit from rFVIIa if it is approved, with the major
      exclusion factor being time.

PMID- 16788302
TI  - Primary stroke unit treatment followed by very early carotid endarterectomy for
      carotid artery stenosis after acute stroke.
AB  - BACKGROUND: Although it is recognized that carotid endarterectomy (CEA) is the
      treatment of choice in symptomatic internal carotid artery (ICA) stenosis, in the
      past, very early CEA has been shown to carry substantial risks. We assessed an
      interdisciplinary concept of very early CEA in patients with high-grade (>70%)
      symptomatic ICA stenosis at a single center. PATIENTS AND METHODS: The course of
      treatment and outcomes of patients who underwent CEA as early as possible after
      being referred to the stroke unit for symptoms of transient ischemic attack and
      stroke were prospectively evaluated, including the following parameters: age,
      severity of ischemia-related symptoms according to the modified Rankin scale,
      duration of symptoms until admission, multimodal imaging findings (color-coded
      duplex, cranial computed tomography, magnetic resonance imaging, positron
      emission tomography), duration until CEA, perioperative course and complications,
      as well as duration of in-hospital care. RESULTS: Fifty consecutive patients
      (median age 68 years, range 44-90) with clinical and imaging signs of transient
      ischemic attack (n = 19) or stroke (n = 31) were included from January 2000 until
      December 2004. All except 1 patient showed a preoperative Rankin < 4. There was a
      median time period of 6 h between the onset of symptoms and admission (range 1 h
      to 15 days) and a median duration of 4 days after admission until operation
      (range 1-21 days). Seven patients underwent CEA of the contralateral, severely
      stenosed ICA after symptomatic ipsilateral ICA occlusion. Four out of 5 patients
      who primarily underwent systemic thrombolysis recovered almost completely. Three
      patients (6%) experienced a clinical deterioration before surgery. In the
      majority of patients (43/50), CEA was performed under local anesthesia with
      selective shunt use which became necessary in 26%. Three patients (6%) had
      postoperative worsening due to new infarcts. In 2 cases, an intracerebral
      hemorrhage occurred, of which 1 remained asymptomatic. In 1 case, surgical
      revision was necessary because of an ICA thrombosis without permanent
      neurological decline. Patients were discharged after a median time of 14.5 days
      (range 4-44). CONCLUSIONS: After careful selection and preparation in a stroke
      unit, patients with acute stroke due to carotid stenosis can undergo very early
      CEA under local anesthesia with a perioperative risk comparable with the risk of
      later endarterectomy, therefore preventing very early stroke recurrences.

PMID- 16788303
TI  - 'Give time a chance' for in-stent restenosis regression.

PMID- 16788305
TI  - Lactobacillus acidophilus as a cause of liver abscess in a NOD2/CARD15-positive
      patient with Crohn's disease.
AB  - INTRODUCTION: The development of a fistula and/or an abscess are major
      complications in patients with Crohn's disease. An abscess can involve any of the
      major viscera, including the liver and spleen. CASE REPORT: A 27-year-old male
      patient with a 6-month history of NOD2/CARD15-positive Crohn's disease with
      stenosis of the terminal ileum, previously treated with corticosteroids, was
      admitted with fever, chills, diarrhea, fatigue and cachexia. Diagnostic work-up
      revealed sepsis, an abscess in the right hepatic lobe, multiple abdominal
      collections and right-sided pleural effusion. It was felt that his poor general
      condition prevented surgical intervention and complex conservative treatment was
      initiated. It consisted of total parenteral nutrition, antibiotics, percutaneous
      drainage of the liver abscess, and thoracocentesis. Pus and blood cultures showed
      Lactobacillus acidophilus. There was a gradual improvement in the patient's
      condition and the liver abscess decreased in diameter from 14 to 2 cm.
      Aminosalicylates and enteral nutrition were gradually introduced. The patient was
      discharged after 9 weeks in good general condition. CONCLUSION: Although
      extremely rarely, L. acidophilus can cause hepatic abscess and sepsis. This can
      be explained by immunologic incompetence due to corticosteroid treatment of
      Crohn's disease.

PMID- 16788304
TI  - Update on clarithromycin resistance in Helicobacter pylori in Hong Kong and its
      effect on clarithromycin-based triple therapy.
AB  - AIM: To determine the antibiotic susceptibility of Helicobacter pylori and
      evaluate the efficacy of a clarithromycin-based triple therapy in relation to
      antibiotic resistance. METHODS: Consecutive patients referred for upper endoscopy
      due to dyspeptic symptoms were recruited. Gastric biopsies were obtained for the
      CLO test, histology and culture. Antibiotic susceptibility was assessed by the E
      test. Patients with H. pylori infection received rabeprazole 20 mg,
      clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days.
      RESULTS: Of 234 patients recruited, 124 were H. pylori-positive and culture was
      successful in 102 patients. The updated prevalences of resistance to
      clarithromycin, amoxicillin and metronidazole were 7.8, 0 and 39.2%,
      respectively. A total of 86 patients received 1-week triple therapy with
      rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice
      daily, and 81 patients attended the follow-up test. Eradication rates by per
      protocol and intention-to-treat analysis were 92.6 and 87.2%, respectively. The
      eradication rate by per protocol was significantly higher in patients with
      clarithromycin-susceptible strains than in those with clarithromycin-resistant
      strains (98.6 vs. 28.6%, p < 0.001). CONCLUSION: Clarithromycin resistance
      reduces the clinical efficacy of clarithromycin-based triple therapy. However,
      due to the low prevalence of clarithromycin resistance, clarithromycin-based
      therapy is still the first choice for clinical use.

PMID- 16788306
TI  - The NK1 receptor antagonist SR140333 inhibits capsaicin-induced ERK
      phosphorylation in sensory neurons.
AB  - Primary sensory neurons respond to a vigorous excitation via the capsaicin
      receptor/TRPV1 cation channel by a phosphorylation of the Jak/STAT pathway as
      measured by phospho-STAT3, and of the Ras/Raf-MAPK pathway as measured by phospho
      MAPK/ERK1/2. In the present investigation a possible involvement of NK1 receptors
      in the capsaicin-induced activation of these signal transduction pathways was
      investigated by protein extraction and Western immunoblotting. Phospho
      MAPK/ERK1/2 and phospho-STAT3 were determined in the dorsal root ganglia (DRG)
      and in the sciatic nerve of rats at 3 and 6 h following a systemic capsaicin
      treatment without or with the pretreatment of the selective NK1 receptor
      antagonist SR140333 (1 mg/kg s.c.; 3 h before capsaicin). Capsaicin evoked a
      threefold increase in phospho-ERK in the sciatic nerve and a two- to threefold
      increase in the DRG at 3 h and 6 h after the treatment. SR140333 markedly
      attenuated the capsaicin-induced increase in phosphorylated ERK. In the sciatic
      nerve the difference was significant at each individual time point (3 and 6 h, p
      < 0.001). In the DRG the difference was significant when the data at 3 h and 6 h
      were combined (p < 0.05), but not when individual time points were considered.
      Capsaicin evoked a four- to fivefold increase in phospho-STAT3 in the sciatic
      nerve and a twofold increase in the DRG at 3 and 6 h after the treatment.
      SR140333 less markedly attenuated the capsaicin-induced increase in
      phosphorylated STAT3: whereas in the sciatic nerve the difference was significant
      when the data at 3 h and 6 h were combined (p < 0.05), no such treatment effect
      of SR140333 was observed in the DRG. The expression of TRPV1 mRNA, a specific
      marker of capsaicin-sensitive small sensory neurons, was investigated by RT-PCR 4
      days after the capsaicin treatment. Treatment of rats with SR140333 had no
      influence on the long-term downregulation of TRPV1 mRNA by capsaicin. Based on
      the present results and previous findings it can be postulated that the capsaicin
      induced ERK phosphorylation in sensory neurons is not a direct effect by
      capsaicin, but that rather substance P release from the stimulated sensory
      neurons with an NK1-mediated nerve growth factor (NGF) production is involved.

PMID- 16788308
TI  - The association between seated immobility and local lower-limb venous
      coagulability in healthy adult volunteers: a simulation of prolonged travel
      immobility.
AB  - This is the first study to examine the hypothesis that prolonged sitting is
      associated with procoagulant changes in the local lower-limb venous system. A
      comparison was made with upper-limb venous changes. Changes in markers of
      thrombin generation, fibrinolysis, endothelial perturbation and
      haemoconcentration were analysed as 10 healthy adult male participants sat for 8
      h. The change in foot volume was estimated. Subjective venous thromboembolism
      assessment was undertaken hourly, along with 2-week and 4-week safety follow-up
      for clinical events. Expected increases in median prothrombin fragments 1 and 2,
      thrombin-antithrombin complex and D-dimer were not observed in either limb. An
      increase greater than 45% in the median tissue plasminogen activator and
      plasminogen activator-1 molar ratio (t-PA/PAI-1), and a decrease greater than 15%
      in median soluble thrombomodulin were noted in both limbs. Median haematocrit
      decreased minimally (1%) in the lower limbs, while the foot volume increased by
      4%. Subjects experienced vague symptoms after 6 h of sitting, but none developed
      symptomatic venous thromboembolism. Upper and lower-limb changes in biomarkers
      did not correlate, except those in t-PA/PAI-1 ratio and plasminogen activator-1.
      Significant correlation was found between changes in the lower-limb t-PA/PAI-1
      ratio and right foot volume. This study originally reveals that even in the lower
      limbs, prolonged daytime cramped sitting is not associated with significant
      procoagulant changes in healthy adult male volunteers, and confirms a previous
      observation that local lower-limb venous changes are not identically reflected in
      the upper limbs.

PMID- 16788309
TI  - Elevated first trimester maternal levels of soluble fibrin polymer are associated
      with lower birthweight in twin gestation.
AB  - We assessed soluble fibrin polymer longitudinally in normal pregnancy,
      thrombophilic pregnancy and twin gestation Thirty-three thrombophilic
      pregnancies, 34 uncomplicated multiple gestations and 23 singleton normal
      pregnancies were studied. Maternal plasma samples were collected in the first (6
      12 weeks), 2nd (13-25 weeks) and 3rd trimesters of pregnancy (26-40 weeks) and
      were stored at -70 degrees C until assay. Soluble fibrin polymer was assayed by
      enzyme-linked immunosorbent assay (ABS, Copiague, New York, USA). Statistical
      analysis were made by Spearman test and Levine's test for equality of variance (P
      < 0.05). First soluble fibrin polymer maternal levels in twin gestation were
      significantly higher than in normal pregnancy and thrombophilic pregnancy, (23.8
      +/- 4.5 mug/ml versus 9.2 +/- 3.1 and 10.0 +/- 2.0 mug/ml respectively, P <
      0.005). Second and third trimester maternal levels of SFP in twins were also
      significantly higher than in normal pregnancy. First trimester soluble fibrin
      polymer was highly correlated with birthweight in twin gestation (r = -1, P <
      0.01). In the third trimester, maternal soluble fibrin polymer correlated with
      placental weight in twin gestation (r = 0.639, P < 0.01). Overall, soluble fibrin
      polymer was correlated with placental weight and birthweight in the three groups
      but this did not reach statistical significance. Elevated maternal plasma levels
      of soluble fibrin polymer in twin gestation may derive from an accelerated
      coagulation process due to extensive vascular remodelling. Current studies are
      underway to determine the utility of soluble fibrin polymer in assessing fetal
      growth abnormalities.

PMID- 16788310
TI  - Increased global fibrinolytic capacity as a clue for activated fibrinolysis in
      pre-eclampsia.
AB  - The aim of this study was to compare fibrinolysis in normal pregnancy and pre
      eclampsia using individual markers of thrombosis and fibrinolysis with the
      contribution of a new parameter, global fibrinolytic capacity. Coagulation was
      determined with thrombin-antithrombin complex and prothrombin fragment 1+2 (F
      1+2) and fibrinolysis markers. Tissue plasminogen activator, plasminogen
      activator inhibitor-1 and global fibrinolytic capacity were determined in 14
      normal pregnancies and 29 women with pre-eclampsia. global fibrinolytic capacity
      was also determined in 14 age-matched healthy women. The Mann-Whitney U test and
      Pearson correlation test were used for statistical analysis. Thrombin
      antithrombin complex, prothrombin fragment 1+2 levels, and global fibrinolytic
      capacity levels in pre-eclamptic women were significantly higher than in women
      with normal pregnancies (P < 0.05). Tissue plasminogen activator, plasminogen
      activator inhibitor-1 levels were also significantly higher in the pre-eclampsia
      group (P < 0.001 and P < 0.05 respectively). No significant correlation was found
      between global fibrinolytic capacity and thrombin-antithrombin complex,
      prothrombin fragment 1+2 levels, tissue plasminogen activator or plasminogen
      activator inhibitor-1 activity. Our results suggest that both thrombin formation
      and fibrinolysis are increased in pre-eclampsia compared with normal pregnancy.
      The increased global fibrinolytic capacity indicates that fibrinolysis remains
      preserved in pre-eclampsia. We suggest that global fibrinolytic capacity may be a
      useful parameter for accurately measuring in-vivo fibrinolysis globally, instead
      of with single parameters which may overlook the complex interactions between
      coagulation and fibrinolytic systems.

PMID- 16788311
TI  - Comparison of a new automated von Willebrand factor activity assay with an
      aggregation von Willebrand ristocetin cofactor activity assay for the diagnosis
      of von Willebrand disease.
AB  - von Willebrand disease (VWD) is caused by quantitative and/or qualitative defects
      of von Willebrand factor (VWF). The HemosIL von Willebrand Factor Activity assay,
      a new automated immunological test to measure VWF activity, was implemented on
      STAC and compared with the von Willebrand ristocetin cofactor activity (VWF:RCo)
      aggregation method. Imprecision and dilution studies were also performed. Within
      run imprecision was 17.2% and between-run imprecision was 8.3% (coefficients of
      variation). Dilution studies showed a linearity between 12.5 and 100%. Passing
      and Bablok regression comparing the HemosIL von Willebrand Factor Activity assay
      and the aggregation method yielded a slope of 1.25 (95% confidence interval: 1.11
      1.38) and intercept of -1.40 (95% confidence interval: -8.07 to 0.00). The
      correlation coefficient was 0.84 (95% confidence interval: 0.78-0.89). With a cut
      off value of 50% for VWF activity, the assay has a sensitivity of 94.1% and a
      specificity of 92.8%, compared with the VWF:RCo aggregation assay with a cut-off
      value of 60% producing a sensitivity of 100.0% (specificity 87.6%). With a cut
      off value of 60%, the HemosIL von Willebrand Factor Activity assay on STAC is a
      reliable assay for VWD. VWF:RCo or other functional testing is still required to
      confirm the diagnosis and for further classification of VWD.

PMID- 16788312
TI  - Adhesion of human platelets to albumin is synergistically increased by
      lysophosphatidic acid and adrenaline in a donor-dependent fashion.
AB  - Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators
      considered important for thrombus formation, and were previously shown to
      synergistically increase platelet aggregation. Here we investigate synergistic
      activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich
      plasma from healthy blood donors together with adrenaline and/or LPA were added
      to protein-coated microplates. Platelets were allowed to adhere and the amount of
      adhesion detected enzymatically. The LPA and adrenaline combination induced a
      synergistic increase of platelet adhesion to a normally non-adhesive albumin
      surface. The degree of synergy varied markedly between individuals; these
      variations could not be explained by age, gender, blood type or different amounts
      of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma.
      There was a trend indicating increased synergistic effect for platelets sensitive
      to adrenaline stimulation. The synergistic effect was blocked by the alpha2
      adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system
      creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3.
      Furthermore, platelets adhering to albumin after adrenaline and LPA treatment
      expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to
      increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2
      adrenoceptor signalling and platelet secretion. We also confirm that synergistic
      platelet activation achieved with LPA and adrenaline is highly donor dependent.

PMID- 16788313
TI  - The intrinsic coagulation activity assay.
AB  - A new assay for the contact-phase-mediated generation of thrombin activity has
      been developed - the intrinsic coagulation activity assay (INCA). Citrated plasma
      (50 microl) is incubated with 5 microl SiO2, 250 mmol/l CaCl2 in polystyrole flat
      bottom wells. After exactly 4 and 5 min (37 degrees C) coagulation reaction times
      (INCA-4 and INCA-5), 100 microl of 2.5 mol/l arginine, pH 8.6, is added to
      inhibit hemostasis activation in the important ascending part of the thrombin
      generation curve and to depolymerize fibrin. After 20 min, 50 microl of 1 mmol/l
      (final concentration 0.24 mmol/l) chromogenic thrombin substrate CHG-Ala-Arg-pNA
      in 1.25 mol/l arginine, pH 8.7, is added. The increase in absorbance is
      determined at 405 nm using a microtiterplate photometer. The assay is calibrated
      against 1 IU/ml thrombin. The normal thrombin activity range of INCA-4 (main
      value) or INCA-5 (control value) is 100 +/- 30% of normal (mean value +/- 1 SD;
      100% = 0.5 IU/ml for INCA-4 and 1.9 IU/ml for INCA-5). With the INCA the normal
      range of intrinsic hemostasis is reflected, low-molecular-weight heparins can be
      monitored, the plasma matrix is not changed significantly, and the assay results
      are a percentage of normal generated thrombin activity and not coagulation
      seconds.

PMID- 16788314
TI  - Role of the B domain in proteolytic inactivation of activated coagulation factor
      VIII by activated protein C and activated factor X.
AB  - Hereditary deficiency of factor VIII (FVIII), haemophilia A, is treated by plasma
      derived FVIII (pd-FVIII) or recombinant FVIII (rFVIII) infusions. B-domain
      deleted FVIII (BDD-rFVIII), although generally safe and effective, was less
      effective than pd-FVIII in prophylaxis -- evidenced by a 2.5-fold higher bleeding
      incidence. Assessment of BDD-rFVIII activity in chromogenic and one-stage
      clotting assays gives up to 50% difference in activity values. As earlier studies
      demonstrated identical activation and cofactor activity of BDD-rFVIII and pd
      FVIII, we decided to study susceptibility of thrombin-activated pd-FVIII, full
      length rFVIII and BDD-rFVIII to proteolytic inactivation by activated protein C
      (APC) and activated factor X (FXa) in a purified system. Proteolysis was
      monitored by Western blot using monoclonal antibodies C5 and R8B12 specific for
      the A1 and A2 domains, respectively. Inactivation was monitored by measuring the
      residual cofactor activity of FVIII forms in a one-stage clotting assay.
      Proteolysis of A1 and A2 domains of activated BDD-rFVIII proceeded 11 or 13 times
      faster than that of pd-FVIII or full-length rFVIII. Inactivation of activated BDD
      rFVIII was two to three times faster by APC and five to six times faster by FXa.
      We suggest that differences in proteolytic inactivation may contribute to
      differences between BDD-rFVIII and pd-FVIII in assaying and in clinical use.

PMID- 16788315
TI  - Elective administration in infants of low-dose recombinant activated factor VII
      (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not
      shorten time to chest closure or reduce blood loss and need for transfusions: a
      randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and
      standard haemostatic replacement therapy versus standard haemostatic replacement
      therapy.
AB  - We investigated the effectiveness of prophylactic administration of recombinant
      activated factor VII (rFVIIa) for cardiopulmonary bypass surgery in children
      under 1 year old with congenital heart disease (CHD) in a double-blinded, placebo
      controlled study. The rFVIIa dose was 40 microg/kg and all patients also received
      standard haemostatic replacement therapy. The primary endpoint was the time to
      chest closure from neutralization of heparin with protamine sulphate as this
      could be most objectively and accurately measured during surgery. Secondary
      endpoints were volumes of transfused blood, platelet concentrates and fresh
      frozen plasma. All adverse events were recorded. In the intention-to-treat
      analysis there were 76 patients (40 in rFVIIa group and 36 in placebo group). The
      demographics and severity of CHD were similar in both groups. No benefit of
      rFVIIa prophylaxis was found in the time to chest closure, which was
      significantly prolonged in the rFVIIa group (rFVIIa mean +/- SE, 98.8 +/- 27.27
      versus 55.3 +/- 29.15, P = 0.0263). In the 41 patients available for a follow-up
      visit 6 weeks after discharge, the chest closure time was also prolonged in the
      rFVIIa group (P = 0.0515). There were no significant differences in the secondary
      endpoints. Adverse events were similar in both groups.

PMID- 16788316
TI  - Efficacy of recombinant activated factor VII in unselected patients with
      uncontrolled haemorrhage: a single centre experience.
AB  - Recombinant activated factor VII (rFVIIa /Novoseven) has been used in a wide
      variety of circumstances as a treatment for uncontrolled bleeding. We present a
      retrospective report of the use of rFVIIa in 40 consecutive patients without
      inherited bleeding disorders in a single centre. Twenty-one (68%) of the 31
      patients whose response to rFVIIa was documented showed a reduction or cessation
      in bleeding; in nine patients (29%) bleeding was unchanged and in one patient
      (3%) bleeding increased despite rFVIIa. One person suffered a thrombotic stroke
      after rFVIIa treatment. There were no other adverse events directly attributable
      to rFVIIa. Twenty-four patients (60%) died during the hospital admission in which
      the rFVIIa was administered. Twelve patients (30%) who received rFVIIa had
      bleeding secondary to haematological malignancy and 21 patients (53%) had
      bleeding complicating a surgical procedure. There were 11 deaths (92%) in the
      haematological malignancy group and 10 deaths (48%) in the surgical group.
      Patients with haematological malignancy received a significantly greater median
      number of doses of rFVIIa than patients with surgical bleeding complications
      (three versus one dose, P = 0.04). We conclude that rFVIIa can be used safely in
      uncontrolled haemorrhage and the majority of patients show a response.

PMID- 16788317
TI  - Identification of human platelet glycoprotein VI-specific IgG autoantibody and
      its fragments.
AB  - Glycoprotein VI (GPVI), as a major receptor for collagen on the platelet surface,
      mediates the initial platelet contact with collagen, and causes platelet
      aggregation and thrombosis. Agents of anti-GPVI can inhibit the adhesion,
      activation and aggregation function of platelets, which can be used for
      preventing thrombotic diseases. To make humanized monoclonal antibodies by phage
      surface display technology, we studied plasmas from 44 patients with chronic
      idiopathic thrombocytopenic purpura using modified monoclonal antibody
      immobilization of platelet antigen assays. GPVI-specific antibodies were found in
      six (13.6%) patients. Among these, only one showed significant inhibition of
      platelet aggregation induced by collagen. The IgG antibody and F(ab')2 fragments
      of this patient's plasma were further purified and their immunoreactivities and
      effects on platelet aggregation were reanalyzed. It was found that purified IgG
      and its F(ab')2 fragments from the patient not only retained the ability to bind
      to platelet GPVI, but also inhibited collagen-induced platelet aggregation. In
      this study, therefore, the specific anti-platelet GPVI autoantibody that inhibits
      collagen-induced platelet aggregation has been successfully screened out, which
      can be used to develop completely humanized anti-GPVI phage antibody.

PMID- 16788318
TI  - Molecular genetics and transfusion management in a child with Bernard Soulier
      syndrome.
AB  - We present a case of Bernard Soulier syndrome in a 9-year-old boy caused by a
      novel genetic mutation. This child was shown to be homozygous for a single
      nucleotide deletion (c.1077delG) in the GP1BA gene not previously reported.
      Clinically, the boy has become refractory to platelet transfusions with both allo
      antibodies and iso-antibodies and a massive transfusion requirement for ongoing
      haemorrhage. We describe the critical role that the blood product transfusion
      continues to play in the management of Bernard Soulier syndrome and discuss
      therapeutic options in these patients.

PMID- 16788319
TI  - Successful use of recombinant activated FVII and aminocaproic acid in four
      neonates with life-threatening hemorrhage.
AB  - Reports on the use of recombinant activated factor VII (rFVIIa) to counteract
      hemorrhagic shock in neonates and preterm infants are increasing. rFVIIa enhances
      thrombin generation in situations with impaired thrombin formation and, since
      thrombin has a crucial role in providing hemostasis, rFVIIa is regarded as a
      general hemostasis agent. Full thrombin generation is necessary for the formation
      of a stable fibrin plug resistant to premature fibrinolysis. Antifibrinolytic
      drugs are not recommended for the treatment of acute bleeding. We report four
      neonates (one with massive postsurgical hemorrhage after ileostomy and three with
      severe pulmonary hemorrhage in the course of mechanical ventilation for meconium
      aspiration syndrome, congenital heart disease and during postoperative
      resuscitation after cardiac surgery for congenital heart disease) who were
      successfully treated with multiple administration of rFVIIa (120 microg/kg per
      dose) and antifibrinolytic therapy - aminocaproic acid (100 mg/kg per dose). In a
      fibrinolytic environment therapeutic concentrations of rFVIIa may sometimes be
      insufficient to produce adequate amounts of thrombin necessary for stable clot
      structure. Laboratory data in three of our patients with pulmonary hemorrhage
      (low fibrinogen levels with slightly prolonged prothrombin time) supported this
      thesis, so we blocked fibrinolysis with aminocaproic acid and achieved a complete
      clinical and laboratory therapeutic effect.

PMID- 16788320
TI  - Resistance of porcine blood clots to lysis relates to poor activation of porcine
      plasminogen by tissue plasminogen activator.
AB  - In-vitro experimentation was performed on porcine and human blood to determine
      their comparative responsiveness to a novel fibrinolytic inhibitor and thereby
      assess whether the pig is a suitable animal model for subsequent in-vivo testing
      of this inhibitor. Thromboelastography showed the clots formed from porcine whole
      blood to be highly resistant to tissue plasminogen activator (t-PA)-catalyzed
      lysis, and this communication offers the resistance of porcine plasminogen to
      activation by t-PA as an explanation. Porcine blood containing 100 and 1500 IU/ml
      added t-PA lysed very slowly, having LY30 values of 1.9 +/- 1.4 and 2.9 +/- 1.9%,
      respectively. In contrast, the LY30 values for the human clots containing 100 and
      1500 IU/ml t-PA were 77.1 +/- 6.3 and 93.3 +/- 1.3%, respectively. Moreover,
      purified porcine plasminogen was activated very slowly by added t-PA in the
      presence of both human and porcine fibrin. Activation of plasminogen by the
      endogenous activators, as measured by the euglobulin clot lysis time, was greatly
      prolonged for the pig (22 +/- 3 h) compared with the human (3.5 +/- 1.5 h). These
      results suggest caution in using the pig as an experimental model when studying
      the effects of various agents on fibrinolysis.

PMID- 16788322
TI  - Preanalytical variables in coagulation testing.

PMID- 16788321
TI  - Impaired platelet adhesion to lysed fibrin, whereas neutrophil adhesion remains
      intact under conditions of flow.
AB  - Vessel wall injury induces the formation of a haemostatic plug. Restoration of
      vascular integrity should involve cessation of further platelet and fibrin
      deposition and subsequent removal of these thrombi by both the fibrinolytic
      system and proteases delivered by infiltrating inflammatory cells. We
      hypothesized that adhesion of platelets and inflammatory cells [polymorphonuclear
      leucocyte (PMN)] to fibrin is differently supported after exposure of fibrin
      during fibrinolysis. Fibrin surfaces were exposed to fibrinolytic agents, and
      platelet and PMN adhesion was studied under conditions of flow. Specific adhesion
      of platelets to preformed fibrin was reduced by fibrinolytic treatment of the
      fibrin. PMN adhesion to fibrin was only slightly affected even after 180 min
      exposure to plasmin. With fibrin still present after fibrinolytic treatment, the
      impaired platelet adhesion seems explained by loss of the primary platelet
      adhesion site gamma400-411 on fibrin. PMN binding to fibrin clearly depends on
      other sites that are less degraded by fibrinolysis. We have shown that PMN
      adhesion in flowing blood to lysed fibrin was still present, whereas platelet
      adhesion was impaired due to the loss of the primary platelet adhesion site
      gamma400-411. Based on our in-vitro perfusion model, we conclude that
      fibrinolysis specifically interferes with the thrombogenicity of fibrin in the
      haemostatic plug, whereas the inflammatory response is preserved. The latter may
      participate in the long-term removal and restructuration of the plug.

PMID- 16788323
TI  - Recurrent reversible dilated cardiomyopathy secondary to viral and streptococcal
      pneumonia vaccine-associated myocarditis.
AB  - Myocarditis is inflammation of cardiac muscle, which may be acute, subacute, or
      chronic with either focal or diffuse involvement of the myocardium. This leads to
      a cardiomyopathy with clinical features of heart failure as well as
      echocardiographic evidence of global dilation of the cardiac chambers. There are
      numerous reports in the literature of viral myocarditis causing dilated
      cardiomyopathy; however, there are no reports of recurrent viral myocarditis and
      vaccine-associated myocarditis in a single patient with complete reversal of the
      cardiomyopathy and return to normal cardiac function. We present a case of
      recurrent myocarditis in a female patient caused by a viral upper respiratory
      infection and streptococcal pneumonia vaccination who presented with recurrent
      episodes of reversible cardiomyopathy.

PMID- 16788325
TI  - Characteristics of patients with cervical spinal injury requiring permanent
      pacemaker implantation.
AB  - Acute cervical spinal cord injury frequently results in bradydysrhythmia, which
      may lead to hypotension and asystole. Such symptoms are more common in the first
      2 weeks after the injury. Treatment modalities include atropine, epinephrine,
      aminophylline, and pacemaker insertion. The criteria for pacemaker use in this
      population are not well defined. We describe characteristics of 3 patients who
      required permanent, transvenous pacemaker implantation for recurrent symptoms. In
      2 of the 3 patients, transcutaneous pacing failed to provide adequate protection.
      Transcutaneous pacemakers are not reliable, as was the case of these patients,
      and early consideration for transvenous pacemaker insertion may be indicated,
      especially in hemodynamically unstable patients. In this report, all 3 patients
      required permanent pacemaker implantation.

PMID- 16788324
TI  - Bidirectional ventricular tachycardia and fatty infiltration of the anterior
      right ventricular free wall.
AB  - We report a 52-year-old woman with palpitations and syncope. Holter recording
      revealed runs of bidirectional ventricular tachycardia, and magnetic resonance
      imaging showed thickening and fatty infiltration of the right ventricle with
      normal cardiac chamber size and no wall motion abnormalities.

PMID- 16788326
TI  - Sudden death associated with anomalous coronary origin and obstructive coronary
      disease in the young.
AB  - Sudden cardiac death in a young patient is a catastrophic occurrence. Anomalous
      coronary origin (ACO) is a significant cause of sudden cardiac death among
      individuals under the age of 35 years. We sought to define the premortem clinical
      and postmortem histopathologic findings in victims of sudden cardiac death
      resulting from either ACO or obstructive atherosclerotic coronary artery disease
      (CAD) among U.S. military recruits (ages 17-35 years). The autopsy records of all
      sudden cardiac deaths occurring among recruits during their basic military
      training period from 1977 through 2001 were reviewed. Twenty-one deaths were
      associated with ACO and 10 with CAD. Recruits with ACO were more likely to have
      prodromal symptoms of exertional syncope and/or chest pain (48% vs. 0%, P =
      0.011). All sudden cardiac deaths resulting from ACO involved a left main
      coronary artery takeoff from the right coronary sinus with a course between the
      aorta and the right ventricular outflow tract and an otherwise normal
      distribution of the major epicardial coronary arteries. Myocardial fibrosis was
      seen equally in those with both CAD and ACO (30% vs. 20%, P = 0.66), but the
      finding of necrosis tended to be more common among recruits with CAD (50% vs.
      15%, P = 0.08). In conclusion, review of autopsy data of sudden cardiac deaths
      among U.S. military recruits reveals myocardial fibrosis or necrosis occurred in
      70% of cases with CAD and 35% of cases with ACO. Sudden cardiac deaths resulting
      from ACO were more likely to be associated with premortem exertional chest
      discomfort and/or syncope compared with deaths resulting from CAD.

PMID- 16788327
TI  - A national survey of cardiovascular physicians' beliefs and clinical care
      practices when diagnosing and treating depression in patients with cardiovascular
      disease.
AB  - A national survey was administered to determine 1) cardiovascular physicians'
      beliefs about the association between depression and cardiovascular disease
      (CVD), 2) the methods used to diagnose depression, 3) referral patterns for
      treatment of depression, and 4) frequency of use and preferred choice of
      antidepressant. A national survey of 50% of randomly selected U.S. cardiovascular
      physicians belonging to the American College of Cardiology was conducted; 796 of
      8854 physicians who received the questionnaires responded. Cardiovascular
      physicians were aware of indirect associations between depression and coronary
      artery disease (CAD). However, 49.9% were unaware of depression as an independent
      cardiac risk factor; 71.2% asked less than half their patients with CAD about
      depression; 79% used no standard screening method to diagnose depression. Among
      cardiovascular physicians, 84.8% reported that between 1% and 50% of their
      patients have depression, and 49.2% indicated that they treat the symptoms of
      depression in their patients with CAD. Cardiovascular physicians often refer
      depressed patients with CAD to mental health professionals and recommend
      exercise, relaxation training, stress management, psychotherapy, and diaries for
      their patients. Among cardiovascular physicians, 55.5% treat depression/CAD with
      antidepressant medication: sertraline (28%), paroxetine (16.1%), fluoxetine
      (10.8%), escitalopram (8.7%), citalopram (7.9%), bupropion (4.4%), tricyclic
      antidepressants (3.8%), and venlafaxine 2.9%.

PMID- 16788328
TI  - Prevalence of left ventricular hypertrophy in persons with and without
      obstructive sleep apnea.
AB  - We investigated the prevalence of left ventricular hypertrophy (LVH) in persons
      with and without obstructive sleep apnea (OSA). Fifty-three persons had a
      nocturnal polysomnogram to diagnose OSA and 2-dimensional echocardiograms to
      measure left ventricular mass. OSA was considered mild if the respiratory
      disturbance index (RDI) was 5 to 15, moderate if the RDI was 15 to 30, and severe
      if the RDI was >30. LVH was diagnosed if the left ventricular mass index was >110
      g/m in women and >134 g/m in men. LVH was present in 21 of 27 persons (78%) with
      moderate or severe OSA, in 6 of 13 persons (46%) with mild OSA, and in 3 of 13
      persons (23%) with no OSA (P < 0.001 comparing moderate or severe OSA with no OSA
      and P < 0.05 comparing moderate or severe OSA with mild OSA). OSA was a
      significant independent predictor of LVH after controlling the confounding
      effects of hypertension with an odds ratio of 3.579 (95% confidence interval,
      1.589-8.058).

PMID- 16788329
TI  - Value of microvolt T-wave alternans for predicting patients who would benefit
      from implantable cardioverter-defibrillator therapy.
AB  - Despite considerable progress in the management of coronary artery disease and
      dilated cardiomyopathy, a substantial proportion of patients remains at the risk
      of life-threatening arrhythmic events. The Multicenter Automatic Defibrillator
      Implantation II and Sudden Cardiac Death Heart Failure studies have conclusively
      demonstrated that prophylactic implantable cardioverter-defibrillator (ICD)
      therapy reduces mortality among subjects with ischemic and nonischemic
      cardiomyopathy but at the expense of potentially unnecessary ICD implantation in
      a large percentage of patients. Microvolt T-wave alternans (MTWA), with a
      negative predictive value greater than 90%, holds promise for selecting the
      patients who would likely and patients not likely to benefit from ICD
      implantation. Accurate identification of high-risk patients by noninvasive MTWA
      may allow for improved widespread screening for sudden death prevention in the
      general population.

PMID- 16788330
TI  - Gender differences in treatment of heart failure and acute myocardial infarction:
      a question of quality or epidemiology?
AB  - Recent articles have inquired about the quality of care for women presenting with
      cardiovascular disease. The Cooperative Cardiovascular Project and the National
      Heart Failure Project, 2 Medicare databases, provide national data to address
      concerns that women receive poorer quality care than men. In these databases, sex
      was not independently associated with the use of beta-blockers, assessment of
      left ventricular ejection fraction, or use of fibrinolytic therapy for acute
      myocardial infarction (MI), nor of angiotensin-converting enzyme (ACE) inhibitor
      prescription for heart failure. Women with MI were slightly less likely to
      receive aspirin and slightly more likely to receive ACE inhibitors. Among
      patients with equivocal indications, men were significantly more likely than
      women to undergo cardiac catheterization, whereas there were no sex differences
      among patients with strong indication. Women were more likely than men to undergo
      percutaneous coronary intervention and less likely to receive coronary artery
      bypass graft surgery. Short-term mortality rates after MI and readmission rates
      after heart failure did not vary significantly by gender; however, risk of
      mortality after heart failure was slightly lower for women. Within multivariate
      models, gender differences in treatment were small and in many cases
      insignificant. These national datasets fail to reveal a strong sex bias in
      treatment among patients aged > or = 65 years.

PMID- 16788331
TI  - Chymase: a new pharmacologic target in cardiovascular disease.
AB  - Chymase is a chymotrypsin-like serine protease stored as an inactive enzyme
      within the secretory granules of mast cells. An important action of chymase is
      the angiotensin-converting enzyme (ACE)-independent synthesis of angiotensin II,
      which occurs immediately after its release into the interstitial tissues after
      vascular injury. Under physiological conditions, the role of chymase is
      uncertain, but under pathologic situations, chymase may have an important role.
      Pharmacologic strategies that serve to inhibit chymase function may prove to be
      useful in the setting of vascular injury.

PMID- 16788332
TI  - The Bachmann Bundle and interatrial conduction.
AB  - The cardiac conduction system (CCS) is responsible for generation and systematic
      conduction of cardiac impulses. The Bachmann Bundle (BB), considered one of its
      several accessory impulse-conducting pathways, plays a fundamental role in
      interatrial conduction. Delay in this pathway leads to prolongation of the P wave
      on the electrocardiogram (interatrial delay or block), which in turn is a
      precursor for atrial tachyarrhythmias, mainly atrial fibrillation and significant
      left atrial electromechanical dysfunction. As such, the magnitude of its sequelae
      has necessitated a flurry of investigations that have been targeted toward its
      prevention and management. Although current studies on the use of angiotensin
      converting enzyme inhibitors and atrial pacing have indeed shown some promise, it
      would be shortsighted to overlook and circumvent the actual underlying lesion-BB
      abnormality. Thus, a thorough understanding of the CCS and interatrial conduction
      is essential. We review current literature on the BB and discuss potential
      mechanisms that affect its conduction.

PMID- 16788333
TI  - Cardiovascular effects of erythropoietin: anemia and beyond.
AB  - We did a PubMed and Cochrane Database System review of different studies on the
      diverse effects of erythropoietin (EPO), focusing mainly on the cardiovascular
      system. The direct erythropoietic action of EPO is well studied and widely used.
      Published studies report dramatic improvement in the course of heart failure with
      EPO treatment. New controlled clinical trials on large and diverse groups of
      patients are warranted. Antiapoptotic effects of EPO are newly discovered,
      opening new horizons in both clinical investigation and therapy. The salvage of
      cardiomyocytes in acute coronary syndromes, limiting the size of myocardial
      infarction and improving functional recovery, is only one of multiple potential
      applications of this effect. Derivatives of EPO with selective antiapoptotic
      properties seem to hold the best prospects for future studies. Heart failure and
      ischemic heart disease are potential areas where adding EPO to the conventional
      treatment may be beneficial.

PMID- 16788334
TI  - Exenatide: a novel incretin mimetic agent for treating type 2 diabetes mellitus.
AB  - Maintaining glycemic control is the primary goal for preventing macrovascular and
      microvascular complications associated with type 2 diabetes. Currently available
      antidiabetic drugs work in different ways to lower blood glucose levels;
      unfortunately, each of them has its tolerability and safety concerns. Exenatide
      is the first drug in a new class known as the incretin mimetic agents. It
      improves glucose control by mimicking the effects of glucagon-like peptide-1, a
      natural mammalian incretin hormone secreted during food intake. Exenatide was
      approved by the U.S. Food and Drug Administration for the treatment of type 2
      diabetes in conjunction with metformin and/or sulfonylurea. The recommended
      dosage is 5 mug to 10 mug twice daily subcutaneously before breakfast and dinner.
      In randomized, placebo-controlled, 30-week clinical studies, exenatide improved
      glycemic control and promoted weight loss of up to 2.8 kg. The most common
      adverse effects were nausea (44%), vomiting (13%), diarrhea (13%), and
      hypoglycemia (5-36%). Hypoglycemia occurred in a dose-dependent fashion. Patients
      should be closely monitored for hypoglycemia, especially when exenatide is added
      to sulfonylurea therapy. Overall, exenatide provides a treatment option for
      patients with type 2 diabetes who fail to obtain glycemic control while on a
      maximum dose of metformin and/or sulfonylurea therapy. It is also an alternative
      therapy for those patients who cannot tolerate other antidiabetic drugs.

PMID- 16788335
TI  - Early access to physical therapy treatment for subacute low back pain in primary
      health care: a prospective randomized clinical trial.
AB  - OBJECTIVES: To evaluate the effects of early access (EA) to physical therapy
      treatment for patients with subacute low back pain compared to access with a 4
      week waiting list. DESIGN: A prospective, randomized clinical trial. SETTING:
      Primary health care. PATIENTS: Sixty consecutive patients with subacute low back
      pain. INTERVENTIONS: Patients were randomized either to EA within 2 days for
      physical examination and individualized physical therapy treatment (n=32) or a
      control group with a 4-week waiting list (n=28). OUTCOME MEASURES: Self
      administrated questionnaires were used for assessment at inclusion, at discharge,
      and at 6 months. Primary outcome measure was pain intensity assessed by Borg
      category scale for ratings of perceived pain. Secondary outcomes included the
      Orebro musculoskeletal pain screening questionnaire, the Roland and Morris
      disability questionnaire, sick-leave, visits to health care, and physical
      therapy. RESULTS: The results showed no significant differences in pain between
      the groups at discharge. At 6 months, the reduction of pain was significantly
      greater in the EA group compared to the control group (P=0.025). Changes in
      secondary outcome measures were not significantly different between groups.
      CONCLUSIONS: This study indicated that EA to physical therapy resulted in greater
      improvement in perceived pain at 6 months compared to later access. In this
      study, EA to physical therapy could be introduced by reorganization without
      additional resources.

PMID- 16788336
TI  - Changes in head and neck position have a greater effect on elbow joint position
      sense in people with whiplash-associated disorders.
AB  - BACKGROUND: It has been shown that perception of elbow joint position is affected
      by changes in head and neck position. Further, people with whiplash-associated
      disorders (WAD) present with deficits in upper limb coordination and movement.
      OBJECTIVES: This study is aimed to determine whether the effect of changes in
      head position on elbow joint position error (JPE) is more pronounced in people
      with WAD, and to determine whether this is related to the participant's pain and
      anxiety levels. METHODS: Nine people with chronic and disabling WAD and 11
      healthy people participated in this experiment. The ability to reproduce a
      position at the elbow joint was assessed after changes in the position of the
      head and neck to 30 degrees , and with the head in the midline. Pain was
      monitored in WAD participants. RESULTS: Absolute elbow JPE with the head in
      neutral was not different between WAD and control participants (P=0.5). Changes
      in the head and neck position increased absolute elbow JPE in the WAD group
      (P<0.05), but did not affect elbow JPE in the control group (P=0.4). There was a
      connection between pain during testing and the effect of changes in head position
      on elbow JPE (P<0.05). DISCUSSION: Elbow JPE is affected by movement of the head
      and neck, with smaller angles of neck rotation in people with WAD than in healthy
      individuals. This observation may explain deficits in upper limb coordination in
      people with WAD, which may be due to the presence of pain or reduced range of
      motion in this population.

PMID- 16788337
TI  - The effect of fear of movement on muscle activation in posttraumatic neck pain
      disability.
AB  - Studies using surface electromyography have demonstrated a reorganization of
      muscle activation patterns of the neck and shoulder muscles in patients with
      posttraumatic neck pain disability. The neurophysiologically oriented "pain
      adaptation" model explains this reorganization as a useful adaptation to prevent
      further pain and injury. The cognitive-behavioral-oriented "fear avoidance" model
      suggests that fear of movement, in addition to the effects of pain, modulates the
      muscle activation level. We analyzed the extent to which pain and fear of
      movement influenced the activation patterns of the upper trapezius muscle during
      the transition from acute to chronic posttraumatic neck pain. Ninety-two people
      with an acute traumatic neck injury after a motor vehicle accident were followed
      up for 24 weeks. Visual analog scale ratings of pain intensity, response on the
      Tampa Scale of Kinesophobia--fear of movement, and surface electromyography of
      the upper trapezius muscles during a submaximal isometric physical task were
      obtained at 1, 4, 8, 12, and 24 weeks after the motor vehicle accident.
      Multilevel analysis revealed that an increased level of both fear of movement (t
      value=-2.19, P=0.030) and pain intensity (t value=-2.94, P=0.004) were
      independently associated with a decreased level of muscle activation. Moreover,
      the results suggest that the association between fear of movement and lower
      muscle activity level is stronger in patients reporting high pain intensity (t
      value=2.15, P=0.033). The contribution of pain intensity to the muscle activation
      level appeared to decrease over time after the trauma (t value=2.58, P=0.011).
      The results support both the "pain adaptation" and the "fear avoidance" models.
      It is likely that the decrease in muscle activation level is aimed at "avoiding"
      the use of painful muscles.

PMID- 16788338
TI  - Topiramate in treatment of patients with chronic low back pain: a randomized,
      double-blind, placebo-controlled study.
AB  - OBJECTIVE: Chronic low back pain (CLBP) is a widespread ailment. The aim of this
      study was to assess the efficacy of topiramate in the treatment of CLBP and the
      changes in anger status and processing, body weight, subjective pain-related
      disability and health-related quality of life during the course of treatment.
      METHODS: We conducted a 10-week, randomized, double-blind, placebo-controlled
      study of topiramate in 96 (36 women) patients with CLBP. The subjects were
      randomly assigned to topiramate (n=48) or placebo (n=48). Primary outcome
      measures were changes on the McGill Pain Questionnaire, State-Trait Anger
      Expression Inventory, Oswestry Low Back Pain Disability Questionnaire and SF-36
      Health Survey scales, and in body weight. RESULTS: In comparison with the placebo
      group (according to the intent-to-treat principle), significant changes on the
      pain rating index of McGill Pain Questionnaire (Ps<0.001), State-Trait Anger
      Expression Inventory Scales (all Ps<0.001), Oswestry Low Back Pain Disability
      Questionnaire (P<0.001), and SF-36 Health Survey scales (all P<0.001, except on
      the role-emotional scale) were observed after 10 weeks in the patients treated
      with topiramate. Weight loss was also observed and was significantly more
      pronounced in the group treated with topiramate than in those treated with
      placebo (P<0.001). Most patients tolerated topiramate relatively well but 2
      patients dropped out because of side effects. DISCUSSION: Topiramate seems to be
      a relatively safe and effective agent in the treatment of CLBP. Significantly
      positive changes in pain sensitivity, anger status and processing, subjective
      disability, health-related quality of life, and loss of weight were observed.

PMID- 16788339
TI  - Effect of disease-related pain on the health-related quality of life of children
      and adolescents with cystic fibrosis.
AB  - OBJECTIVES: The authors' objective was to describe the effect of recurrent pain
      symptoms on the health-related quality of life (HRQOL) of children and
      adolescents with cystic fibrosis (CF). Frequent pain, independent of disease
      severity, was hypothesized to be associated with broad decrements in physical,
      psychological, and social functioning. METHODS: Forty-six children and
      adolescents (mean age 12.9 years; 52% female) completed the Cystic Fibrosis
      Questionnaire-Revised (CFQ-R) to assess their HRQOL and a retrospective pain
      interview to assess pain location, frequency, intensity, duration, and bother
      during a routine clinic visit. Forced expiratory volume in 1 second as percent of
      predicted (FEV1%) was recorded from medical charts to assess the children's
      disease severity. RESULTS: As hypothesized, pain symptoms were related to
      children's physical, emotional, and role functioning, CF-related symptoms, and
      overall perception of their health. Children with frequent pain had significantly
      reduced physical functioning, vitality, role limitations, and overall perceptions
      of their health, and increased eating disturbances, treatment burden,
      respiratory, and digestive symptoms compared with children with no pain or less
      frequent pain. After controlling for the effects of disease severity, pain
      frequency continued to predict children's HRQOL in each of these areas.
      DISCUSSION: Children with frequent CF-related pain experienced broad decrements
      in their HRQOL. These findings are similar to those found in other populations of
      children experiencing disease-related pain, suggesting a pervasive impact of pain
      on overall health and well-being. Future research is needed to evaluate
      treatments to reduce pain symptoms and improve HRQOL in children with cystic
      fibrosis.

PMID- 16788340
TI  - Ultrasound-guided facet joint injections in the middle to lower cervical spine: a
      CT-controlled sonoanatomic study.
AB  - OBJECTIVES: The aim of this study was to investigate the efficacy of ultrasound
      as a guiding tool for simulated cervical facet joint injections in cadavers.
      METHODS: A total of 40 ultrasound examinations at 5 levels (C6-7 to C2-3) were
      performed on 4 embalmed cadavers. The zygapophyseal joints were located with
      ultrasound. First, the transverse processes of C6 and C7 were established and the
      facet joint of C6-7 was demonstrated. The midpoint of this joint space, defined
      as the middle of its cranio-caudal extension on its lateral surface, was taken as
      a reference point. Ipsilateral distances (A, B, C, and D) between this point and
      each one of the 4 facet joints of the cervical spine up to the facet joints C2-3
      were then computed. Subsequently, coronal computed tomography (CT) scans were
      taken to verify these distances. In a second experiment, a spinal needle was
      advanced under ultrasound guidance to the zygapophyseal joints from C2-3 to C6-7
      on both sides of 1 cadaver. The exact placement of the needle tips was again
      verified by CT. RESULTS: In 4 attempts, a depiction of the joint space was not
      possible. Ultrasound and CT provided the same mean measurements of 1.2+/-0.2 cm,
      2.0+/-0.3 cm, 3.0+/-0.2, and 4.0+/-0.5 cm for distances A, B, C, and D,
      respectively. All 10 needle tips were located in the joint space during simulated
      facet joint injections, as also verified by CT. DISCUSSION: This preclinical
      study suggests that ultrasound is a useful guiding tool for facet joint
      injections in the cervical spine.

PMID- 16788341
TI  - Superior hypogastric block: transdiscal versus classic posterior approach in
      pelvic cancer pain.
AB  - OBJECTIVE: The classic posterior approach of superior hypogastric block has
      several technical difficulties. The transdiscal approach is a novel and easier
      approach for superior hypogastric which overcome these technical difficulties.
      METHODS: Thirty patients were randomly allocated to two groups: The transdiscal
      group and the classic group; visual analog scale pain scores, daily morphine
      consumption, duration of the procedure and side effects were recorded. RESULTS:
      The duration of the procedure was significantly decreased in the transdiscal
      group (24.4+/-5.6 min) compared to the classic group (57.9+/-9.8 min). There were
      no significant differences between the 2 groups in daily morphine consumption and
      VAS pain scores. There was no discitis, disc rupture, or herniation in the
      transdiscal group. CONCLUSION: The transdiscal approach for superior hypogastric
      plexus block in pelvic cancer pain is easier, safer, and more effective with less
      side effects than the classic approach.

PMID- 16788342
TI  - Myofascial disorders in the trochlear region in unilateral migraine: a possible
      initiating or perpetuating factor.
AB  - OBJECTIVE: Some patients with trochlear disorders have been found to suffer from
      concurrent migraine. However, a trochlear examination is not systematically done
      in patients with migraine. Moreover, a search for myofascial trigger points in
      the superior oblique muscle has never been reported in these patients. METHODS:
      The trochlear region was examined in 20 participants with strictly unilateral
      migraine without side-shift and in 20 controls. Referred pain elicited by
      different maneuvers during manual palpation (ie, maintained pressure, active
      muscle contraction, and stretching of the superior oblique muscle) was assessed
      with a visual analog scale. All participants were headache free on the day of
      evaluation. RESULTS: Sixteen participants with migraine (80%) perceived referred
      pain on examination of the trochlear area. It was described as a tightening
      sensation in the retro-orbital region, sometimes extending to the supraorbital
      region and the homolateral forehead. In 15 participants with migraine, both the
      active contraction and the stretching of the muscle increased the referred pain,
      which was consistent with definite myofascial trigger points. All the definite
      trigger points were ipsilateral to the side of the headache. Conversely, only 5
      controls (20%) had referred pain. None of them had definite myofascial trigger
      points because muscle stretching did not increase the intensity of pain. The
      intensity of referred pain at each stage of the trochlear examination was greater
      in subjects with migraine than in controls (P<0.001). CONCLUSION: Patients with
      unilateral migraine commonly perceive referred pain from the trochlear area that
      probably comes from the myofascial trigger points. Myofascial disorders in the
      trochlear region might contribute to the perpetuation of concomitant migraine.

PMID- 16788343
TI  - Predictors of incident chronic widespread pain among veterans following the first
      Gulf War.
AB  - OBJECTIVE: We sought to determine the predictors of incident chronic widespread
      pain (CWP), specifically, the effect of preexisting symptoms, stress, and
      psychosocial factors in the subsequent development of CWP among veterans from the
      first Gulf War (GW). METHODS: We conducted a structured telephone survey
      (baseline) of military personnel originally from Iowa who were either eligible
      for or deployed to Operation Desert Shield/Desert Storm, approximately 5 years
      postconflict. We conducted a follow-up, clinical, in-person study of those who
      met a priori-defined outcomes of symptoms of cognitive dysfunction, depression,
      or CWP, and also a sample of those who did not meet any of the outcomes of
      interest. RESULTS: A total of 370 of 602 evaluated GW veterans were free of CWP 5
      years postconflict. At follow-up, 69 (19%) of these had developed CWP. A positive
      family history of medically unexplained persistent symptoms [odds ratio (OR)=4.8
      (2.3, 13.2)] was strongly associated with CWP. At baseline, individuals who
      reported preexisting symptoms of bronchitis [OR=4.9 (1.9, 12.3)] and cognitive
      dysfunction [OR=2.1 (1.1, 4.2)] were more likely to develop CWP. Alcohol use
      [OR=0.2 (0.1, 0.7)] was protective against CWP. Rather than combat-related
      exposure per se, the perception of stress at the time of the GW [OR=1.6 (1.1,
      2.3)] correlated with CWP. DISCUSSION: Among the GW veterans evaluated
      longitudinally in this study, family history, predeployment symptoms, and the
      level of perceived stress during the GW were associated with subsequent
      development of CWP.

PMID- 16788344
TI  - Comparison of Short Form-36 and Migraine Disability Assessment questionnaire in
      patients with migraine.
AB  - BACKGROUND: The Short Form-36 (SF-36) and Migraine Disability Assessment (MIDAS)
      questionnaires are two of the most commonly used tools to measure outcomes in
      people suffering from headaches. Nevertheless, little is known about their
      interrelationship in patients with headache. OBJECTIVES: The aim of this study
      was to investigate the interrelationship between SF-36 and MIDAS questionnaires
      in patients with migraine. METHODS: We enrolled 231 patients with migraine
      (male/female: 43/188, mean age 35.3+/-8.1) who visited our headache clinic. They
      completed the SF-36, MIDAS, and a headache intake form. RESULTS: The correlation
      coefficients between the MIDAS score and 8 domains of the SF-36 ranged from -0.30
      for the mental health domain to -0.53 for the social functioning domain (P<0.01).
      Canonical correlation analysis showed that the overall overlap between the 2
      instruments was moderately strong (canonical correlation coefficients r=0.707 and
      0.572). The overall measured redundancies for MIDAS and SF-36 scales in this
      study were 35.4% and 11.5%, respectively. The stepwise linear regression model
      showed that the social functioning domain alone explained 27.9% of variance in
      the MIDAS scores. Bodily pain, physical functioning, and general health domains
      added an additional 11.4% of the explained variance in the regression model.
      CONCLUSION: Despite the fact that these two measures were considerably
      correlated, the MIDAS and SF-36 were found to measure different aspects of the
      impact of headache for the sample investigated. The MIDAS questionnaire does not
      cover the emotional domain; therefore, an accompanying psychological
      questionnaire might help assess the outcome for headache studies.

PMID- 16788345
TI  - Pain Assessment in Noncommunicative Elderly persons--PAINE.
AB  - OBJECTIVES: We describe the validation of an informant-based pain assessment for
      persons suffering from dementia called Pain Assessment in Noncommunicative
      Elderly persons (PAINE) using 2 different samples. METHODS: In the first study,
      the participants included 80 residents from one nursing home. We assessed
      internal consistency using Cronbach alpha, interrater and test-retest reliability
      using Pearson correlations, and validity using receiver operating characteristic
      curve analyses, comparing PAINE to these criteria on the basis of reports from
      physicians, nurses, relatives, and the residents themselves. In the second study,
      the participants included 91 residents from 2 different nursing homes. We
      assessed validity by correlating scores on PAINE with those from other
      assessments designed to detect pain. RESULTS: PAINE shows adequate internal
      consistency and both interrater and test-retest reliability. It also shows
      adequate receiver operating characteristic curve results and reasonable
      correlations with the existing measures of pain in persons with dementia.
      DISCUSSION: PAINE has the advantage of using a comprehensive list of pain
      symptoms on the basis of systematic questioning of direct caregivers from several
      institutions. The validity results suggest that this assessment could be a useful
      tool in detecting pain in persons with dementia.

PMID- 16788346
TI  - Adolescent-parent relationships in the context of adolescent chronic pain
      conditions.
AB  - OBJECTIVE: This study explored adolescent-parent relationships in families of
      adolescents with chronic pain. METHODS: A retrospective review was conducted on
      112 adolescents with chronic pain who presented for clinical evaluation at an
      outpatient pediatric multidisciplinary pain management clinic. Adolescents
      reported on pain severity and duration, functional disability, and psychological
      distress. Parents responded to a measure of adolescent-parent relationship
      distress. RESULTS: The findings show that as a group, parents of adolescents with
      chronic pain syndromes reported less adolescent-parent relationship distress
      compared to normative data. Adolescent-parent relationship distress was inversely
      correlated with pain severity. A multiple regression model containing indicators
      of global psychological distress, pain severity, and adolescent-parent
      relationship distress predicted levels of adolescents' functional disability.
      Pain severity and functional disability were more closely linked at the low end
      of Adolescent-Parent Relationship Domain scores. DISCUSSION: The findings suggest
      important directions for future research to advance our understanding of the role
      of adolescent-parent relationships in the pain-disability cycle.

PMID- 16788348
TI  - Assessing adverse childhood experiences in chronic pain: it does matter.

PMID- 16788351
TI  - An introduction to technology for patient-centered, collaborative care.
AB  - "Patient-centered, collaborative care" is healthcare jargon. But underlying the
      jargon is the principle that a patient who receives such care strongly agrees
      that "I receive exactly the healthcare I want and need exactly when and how I
      want and need it." Currently only about 1 in 4 Americans who have adequate
      financial resources can make this claim. Think of a pyramid. At the apex is the
      highest level of "patient-centered, collaborative care." At the base are measures
      about "what's the matter" (from the clinical perspective) and "what matters"
      (from the patient perspective). As patients and clinicians act collaboratively on
      these measures, they climb closer to the apex of the pyramid. Given the realities
      of healthcare in the Unites States, should busy professionals take time to think
      about ways to climb pyramids? In this "Introduction" we describe why the answer
      to this rhetorical question ought to be "yes." In the articles that comprise this
      issue, readers will learn how technology that supports patient-centered,
      collaborative care can help bridge the gap between desirable goals and limited
      time. All the authors understand technology (such as hardware and software), and
      the way humans use the technology (called techne) will not overcome the many
      obstacles to the attainment of patient-centered, collaborative care.
      Nevertheless, we are hopeful that the examples described in these articles
      suggest ways that significant progress toward patient-centered, collaborative
      care can be made. The articles are practical. The results are persuasive. It is
      worth the climb!

PMID- 16788352
TI  - Patients report positive impacts of collaborative care.
AB  - Collaborative Care refers to a partnership between healthcare professionals and
      patients who feel confident to manage their health conditions. Using an Internet
      based assessment of health needs and healthcare quality, we surveyed 24,609 adult
      Americans aged 19 to 69 who had common chronic diseases or significant
      dysfunction. In these patients, we examined the association of Collaborative Care
      with specific measures for treatment effect, disease control, prevention, and
      economic impacts. These measures were adjusted for respondents' demographic
      characteristics, burden of illness, health behaviors, and overall quality of
      healthcare. Only 21% of respondents participated in good Collaborative Care, 36%
      attained fair Collaborative Care, and 43% experienced poor Collaborative Care.
      Regardless of overall care quality or the respondents' personal characteristics,
      burden of illness, or health behaviors, good Collaborative Care was associated
      with better control of blood pressure, blood glucose level, serum cholesterol
      level, and treatment effectiveness for pain and emotional problems. Some
      preventive actions were better, and some adverse economic impacts of illness were
      mitigated.

PMID- 16788353
TI  - Resource planning for patient-centered, collaborative care.
AB  - In this article, we use self-reported information from 13,271 older adults and
      the results from several controlled trials to construct a planned-care management
      strategy that cuts across diseases and conditions and also addresses health
      disparities attributed to low socioeconomic status. Three strata result from the
      interaction of patients' financial status, the presence or absence of bothersome
      pain and psychosocial problems, and their confidence with self-care. A majority
      of ambulatory patients generally fall in the first stratum. More resources are
      required in the 2 remaining strata to attain patient-centered, collaborative
      care. Because the planned-care management strategy is behaviorally sophisticated,
      it is likely to be more efficient and effective than strategies based on concepts
      of disease management that focus on either a single disease or groupings of
      patients who are "high utilizers" of healthcare. We conclude that modern
      technologies and related approaches make resource planning for patient-centered,
      collaborative care feasible and desirable.

PMID- 16788354
TI  - The emergence of Ideal Micro Practices for patient-centered, collaborative care.
AB  - Ideal Micro Practices are capable of delivering patient-centered collaborative
      care. With respect to comparable adult patients in "usual" care settings, twice
      as many patients who use Ideal Micro Practices report they receive care that is
      "exactly what they want and need exactly when and how they want and need it" (68%
      vs 35%). Compared to usual care, these very small, low-overhead practices are
      more likely to have patients report very high levels of continuity (98% vs 88%),
      efficiency (95% vs 73%), and access (72% vs 53%). Patient ratings of very good
      information (83% vs 67%) and clinician awareness of pain or emotional problem are
      also higher (87% vs 69%). However, only a slim majority of patients using Ideal
      Micro Practices report that they are confident in their ability to manage and
      control their health problems or concerns. Ideal Micro Practices are sharing new
      tools and approaches to better understand their patients' needs and increase
      patients' confidence in their ability to manage conditions. In addition, these
      practices are working collaboratively to standardize their approaches and make
      the essential elements of Ideal Micro Practice replicable.

PMID- 16788355
TI  - "Patient Portals" and "E-Visits".
AB  - "Patient Portals" enable patients to review their medical record and add
      information to it. Clinics are using "E-Visits" to substitute for a face-to-face
      office visit. This article describes the experience of one healthcare system with
      "Patient Portals" and "E-Visits."

PMID- 16788356
TI  - Engaging Quad/Graphics employees in the improvement of their health and
      healthcare.
AB  - In an era when rising healthcare costs threaten the competitiveness of American
      businesses in an increasingly global marketplace, we describe Quad/Graphics on
      site primary care (QuadMed) clinics tightly integrated with wellness, fitness,
      rehabilitation, and occupational medicine. We further describe the Lean You
      wellness program recently put in place to stem the rising burden of obesity. The
      Lean You program illustrates how an integrated employer and health provider
      system can become even more engaged in collaborative care with its employees.
      Financial and clinical data suggests that at Quad/Graphics-QuadMed, these full
      service health service approaches are effective.

PMID- 16788357
TI  - Patient-centered collaborative care: employer-led business coalition vision for
      action.
AB  - Employers influence healthcare delivery. Two spheres of influence include (i)
      what is done at each worksite and by each employer (plan design and
      communications as well as health plan contracting) and (ii) what is done
      collectively in both private and public sectors to address performance and to
      encourage the physicians to adopt practice changes. The need for change toward
      patient-centered care is the subject of this article.

PMID- 16788359
TI  - Technical notes: when all things are not equal.
AB  - This article addresses 2 questions. First, how useful is adult patients'
      information about health and healthcare when they use the Internet for a "health
      checkup"? We find that patietns' reports are very strongly associated with
      medical record information for blood pressure, cholesterol, and blood glucose.
      Second, what are the biases in information from Internet respondents? Although we
      find that "health checkup" Internet users seem to be representative for patients
      in actual practice, much more research will be needed to fully address this
      question.

PMID- 16788358
TI  - Postscript: health disparity and collaborative care.
AB  - In this report, we compare healthcare processes for patients with low (n = 7467)
      and adequate financial status (n = 43,701) after adjustment for age, gender,
      burden of illness, and health behaviors. Patients with low financial status were
      10% to 30% less likely to report good service and collaborative care; they report
      that markers of disease management and prevention were 7% to 18% below the levels
      of patients with adequate income. From the patient perspective, these results
      confirm that inadequate financial status has a broad and adverse influence on
      health and healthcare. Technology for patient-centered, collaborative care alone
      will not remedy the problem of health disparity.

PMID- 16788360
TI  - Increased introduction, advertising, and sales of preventive drugs during 1986
      2002 in Sweden.
AB  - The objective of this study was to survey how introduction of new drugs and
      promotional activities influence drug sales in Sweden. All drugs on the Swedish
      market were categorized as curative, symptom-alleviating, substitutive, or
      preventive. The number of new drugs introduced, drug sales in volume and value,
      and the number of drug advertisements appearing in the major Swedish medical
      journal during 1986-2002 were determined for each of the 4 drug categories.
      Between 1986 and 1998, the relative shares of the 4 drug categories were
      relatively constant. From 1998 to 2002, the share of new preventive drugs
      increased from 24% to 30%, their share of advertisements increased from 20% to
      35%, and their sales value increased from 25% to 30%. During the same period, the
      shares of other drugs decreased correspondingly. Pharmaceutical companies have
      shifted their attention to the introduction, advertising, and sales of preventive
      drugs in an attempt to exploit preventive medicine. This might lead to waste of
      resources when expensive preventive drugs are used by numerous patients over many
      years, as the benefit of preventive drugs for the individual patient cannot be
      judged easily.

PMID- 16788362
TI  - A "just culture" proves just right.

PMID- 16788364
TI  - Collaboration key to successful practice initiatives.

PMID- 16788365
TI  - Automation: the vanguard of EBN.

PMID- 16788366
TI  - Change agents bolster new practices in the workplace.

PMID- 16788367
TI  - Limit life-sustaining treatments with crucial communication.

PMID- 16788368
TI  - Patient safety: through the eyes of your peers.
AB  - Increase nursing accountability and reduce the potential for adverse events with
      a peer review model.

PMID- 16788370
TI  - Step up care for diabetic foot.
AB  - Nurses are integral to helping patients preventa common diabetes complication
      that threatens life and limb.

PMID- 16788372
TI  - Policy and procedure management: a job that's never done.
AB  - Accreditation, technology, procedures, and medications call for a constant focus
      on creating new or revising current regulations that govern nursing practice.

PMID- 16788373
TI  - Create a blueprint for successful hospital construction.
AB  - Smoothly transition your department, staff, and patients from old to new areas.

PMID- 16788374
TI  - Shared governance and EBP: a logical partnership?
AB  - While the relationship between shared governance and evidence-based practice is
      still in its early stages, the Albert Einstein Healthcare Network believes these
      separate models of care share the same processes and equate to solid, successful
      nursing.

PMID- 16788375
TI  - Online patient assignments enhance horizontal communication.

PMID- 16788376
TI  - Liposomes: a new way to deliver pain medications.

PMID- 16788377
TI  - Financial reimbursement.

PMID- 16788378
TI  - Naturally occurring mutation Leu307Pro of human butyrylcholinesterase in the
      Vysya community of India.
AB  - BACKGROUND: People with genetic variants of butyrylcholinesterase (EC 3.1.1.8,
      BChE) can have hours of prolonged apnea after a normal dose of succinylcholine or
      mivacurium. METHODS: Plasma samples from 226 people in the Vysya community in
      Coimbatore, India were tested for BChE activity. RESULTS: Nine unrelated
      individuals had no detectable activity. DNA sequencing revealed a novel mutation
      in exon 2 of the BCHE gene, responsible for the silent phenotype of human serum
      BChE. All silent BChE samples were homozygous for a point mutation at codon 307
      (CTT-->CCT), resulting in substitution of leucine 307 by proline. Western blot
      analysis with a monoclonal antibody showed no BChE protein in plasma. Silent BChE
      plasma samples had no organophosphate-reactive BChE, as measured with FP-biotin.
      Expression of recombinant Leu307Pro BChE in cell culture confirmed that this
      mutant is expressed at very low levels. The proline substitution most likely
      destabilizes the BChE structure and causes the protein to be misfolded and
      rapidly degraded. CONCLUSIONS: This is the first report of a molecularly defined
      BChE mutation in the Indian population. The frequency of homozygous silent BChE
      in the Vysya community is 1 in 24, a value 4000-fold higher than the frequency of
      homozygous silent BChE in European and American populations.

PMID- 16788379
TI  - Polymorphisms in O6-methylguanine DNA methyltransferase and breast cancer risk.
AB  - OBJECTIVE: Endogenous and exogenous estrogens influence breast cancer risk by
      interacting with estrogen receptor (ER). The O-methylguanine DNA
      methyltransferase (MGMT) gene has a dual role in repairing alkylation damage and
      in inhibiting ER-mediated cell proliferation. We assessed the two MGMT
      polymorphisms, Leu84Phe and Ile143Val, with breast cancer risk. We also evaluated
      the potential interactions between the two polymorphisms and estrogen-related
      risk factors and cigarette smoking on breast cancer risk. METHODS: We conducted a
      nested case-control study within the Nurses' Health Study (1311 cases, 1760
      controls). RESULTS: Compared with the 84Leu/Leu genotype, the Phe/Phe genotype
      had a multivariate odds ratio (OR) of 1.68 (95% confidence interval (CI), 0.98
      2.88). This positive association was magnified among postmenopausal women with
      body mass index>25 (OR, 3.01; 95% CI, 1.30-6.94), those in the highest tertile of
      pre-diagnostic plasma endogenous estradiol levels (Phe carriers versus non
      carriers, OR, 2.42; 95% CI, 1.49-3.94), non-current postmenopausal hormone users
      (OR, 2.60; 95% CI, 1.19-5.64), and possibly estrogen receptor-positive cases (OR,
      1.82; 95% CI, 0.99-3.35). We did not observe a main effect of the Ile143Val
      polymorphism or its interactions with these factors. No interaction was observed
      between either of the polymorphisms and cigarette smoking on breast cancer risk.
      CONCLUSIONS: These data suggest that the Leu84Phe polymorphism affect the
      capacity of MGMT to inhibit estrogen receptor-mediated cell proliferation and is
      associated with breast cancer risk.

PMID- 16788380
TI  - Cyclin D1 and epidermal growth factor polymorphisms associated with survival in
      patients with advanced colorectal cancer treated with Cetuximab.
AB  - The study aimed to investigate whether polymorphisms in genes of the EGFR
      signaling pathway are associated with clinical outcome in advanced colorectal
      cancer (CRC) patients treated with single-agent Cetuximab. Polymorphisms of
      interest in the EGFR pathway include: cyclin D1 (CCND1) A870G, cyclooxygenase 2
      (Cox-2) G-765C, epidermal growth factor (EGF) A61G, epidermal growth factor
      receptor (EGFR) codon R497 K, EGFR CA dinucleotide repeat in intron 1,
      interleukin (IL)-8 T-251A and vascular endothelial growth factor (VEGF) C936 T
      gene polymorphisms. Thirty-nine metastatic CRC patients were enrolled in the IMCL
      0144 trial and treated with single-agent Cetuximab. Using the polymerase chain
      reaction-restriction fragment length polymorphism method, gene polymorphisms of
      CCND1, COX-2, EGF, EGFR, IL-8 and VEGF were assessed from genomic DNA extracted
      from blood samples. A significant association was found between the CCND1 A870G
      polymorphism and overall survival in our 39 CRC subjects. Patients with the AA
      homozygous genotype survived for a median of 2.3 months [95% confidence interval
      (CI)=2.1-5.7], whereas those with any G allele (AG, GG genotype) survived for a
      median of 8.7 months (95% CI=4.4-13.5) (P=0.019, log-rank test). When we analysed
      the cyclin D1 and EGF polymorphisms together, patients with favourable genotypes
      (EGF any A allele and CCND1 any G allele) showed a median survival time of 12
      months (95% CI=4.8-15.2), whereas patients with any two unfavourable genotypes
      (EGF GG or CCND1 AA) showed a median survived time of 4.4 months (95% CI=2.1-5.7)
      (P=0.004, log-rank test). The findings of this pilot study suggest that the
      cyclin D1 A870G and the EGF A61G polymorphisms may be useful molecular markers
      for predicting clinical outcome in CRC patients treated with single-agent
      Cetuximab.

PMID- 16788381
TI  - Bone morphogenetic protein 15 (BMP15) alleles predict over-response to
      recombinant follicle stimulation hormone and iatrogenic ovarian hyperstimulation
      syndrome (OHSS).
AB  - OBJECTIVE: Controlled ovarian stimulation (COS) using recombinant follicle
      stimulating hormone (rFSH) is the main treatment in assisted reproduction. We
      performed a pharmacogenetic analysis of bone morphogenetic protein 15 (BMP15)
      gene using single nucleotide polymorphisms (SNPs) in COS. We also investigated
      the role of the BMP15 gene in ovarian hyperstimulation syndrome (OHSS). METHODS:
      We analysed different intragenic SNPs located within the BMP15 gene in 307 women
      treated with rFSH, evaluating its involvement in COS outcome. RESULTS: First, we
      analysed two polymorphisms, by applying different tests for genetic association,
      and we found a minimum P-value in patients producing > or =12 follicles in COS
      (high responders) in both polymorphisms of the BMP15 gene. Using bi-directional
      DNA sequencing, we identified two additional single nucleotide DNA variants.
      Second, we conducted association studies with all polymorphisms together, and
      noticed that none of them seemed to fully explain the association of the BMP15
      gene with over-response to rFSH. However, N103S missense mutation is predicted to
      disrupt the secondary structure of human BMP15 protein and is weakly associated
      with OHSS. This coding mutation of the BMP15 gene may partially explain the
      results obtained during our research. Using Thesias software, we reconstructed
      haplotypes with the four intragenic variants and calculated their frequencies in
      normal and over-responders to rFSH. The haplotype TGGA was over-represented in
      high responders when compared with the rest of patients. Moreover, this
      association was higher in patients with OHSS, with a significant global
      haplotypic effect of the BMP15 gene. CONCLUSION: Our results suggest a direct
      relationship between increased follicle production during COS and BMP15 alleles
      in response to rFSH in humans. The use of BMP15 markers to prevent OHSS is also a
      possibility that requires thorough evaluation.

PMID- 16788382
TI  - Four novel defective alleles and comprehensive haplotype analysis of CYP2C9 in
      Japanese.
AB  - Genetic variations in cytochrome P450 2C9 (CYP2C9) are known to contribute to
      interindividual and interethnic variability in response to clinical drugs such as
      warfarin. In the present study, CYP2C9 from 263 Japanese subjects was
      resequenced, resulting in the discovery of 62 variations including 32 novel ones.
      In addition to the two known non-synonymous single nucleotide polymorphisms
      (SNPs), Ile359Leu (*3; allele frequency=0.030) and Leu90Pro (*13; 0.002), seven
      novel non-synonymous SNPs, Leu17Ile (0.002), Lys118ArgfsX9 (*25; 0.002),
      Thr130Arg (*26; 0.002), Arg150Leu (*27; 0.004), Gln214Leu (*28; 0.002), Pro279Thr
      (*29; 0.002) and Ala477Thr (*30; 0.002), were found. Functional characterization
      of novel alleles using a mammalian cell expression system in vitro revealed that
      *25 was a null allele and that *26, *28 and *30 were defective alleles. The *26
      product showed a 90% decrease in the Vmax value but little change in the Km value
      towards diclofenac. Both *28 and *30 products showed two-fold higher Km values
      and three-fold lower Vmax values than the *1 allele, suggesting the importance of
      Gln214 and Ala477 for substrate recognition. Linkage disequilibrium and haplotype
      analyses were performed using the detected variations. Only five haplotypes
      (frequency >0.02) accounted for most (>87%) of the inferred haplotypes, and they
      were closely associated with the haplotypes of CYP2C19 in Japanese. Although the
      haplotype structure of CYP2C9 was rather simple in Japanese, the haplotype
      distribution was quite different from those previously reported in Caucasians and
      Africans. Taken together, novel defective alleles and detailed haplotype
      structures would be useful for determining metabolic phenotypes of CYP2C9
      substrate drugs in Japanese and probably Asians.

PMID- 16788384
TI  - The caudal-related homeodomain protein Cdx2 and hepatocyte nuclear factor 1alpha
      cooperatively regulate the UDP-glucuronosyltransferase 2B7 gene promoter.
AB  - The gastrointestinal tract, contains several UDP-glucuronosyltransferases (UGTs)
      of the UGT1A and UGT2B subfamilies. UGT2B7 is one particular enzyme expressed
      throughout the gastrointestinal tract that possesses broad substrate specificity
      towards orally administered drugs. Because the caudal-related homeodomain protein
      2 (Cdx2) regulates many gastrointestinal properties, we sought to determine
      whether it could regulate the UGT2B7 promoter in the colon-derived cell line Caco
      2. Levels of Cdx2 and UGT2B7 were measured in differentiated and non
      differentiated Caco-2 cells by the quantitative polymerase chain reaction. The
      capacity of the UGT2B7 gene promoter to drive expression of the luciferase
      reporter gene was assessed by transfection into Caco-2 cells, with transcription
      factor expression plasmids. Mutation of putative transcription factor binding
      sites and electrophoretic mobility shift assays were used to define important
      regulatory regions of the UGT2B7 gene promoter. The levels of Cdx2 and UGT2B7
      mRNAs were co-ordinately increased in differentiated Caco2 cells compared to non
      differentiated cells. Cdx2 activates the UGT2B7 proximal promoter by binding to
      two adjacent sites. Promoter activation requires Cdx2 binding to both sites
      wherein these proteins interact to form a putative functional dimer. Dimerization
      was shown to be dependent on redox state using extracts depleted of
      dithiothreitol. In addition, Cdx2 was shown to cooperatively activate the UGT2B7
      promoter in conjunction with hepatocyte nuclear factor 1alpha (HNF1alpha), a
      mechanism previously observed to regulate other intestine-specific genes. The
      present study is the first to define transcription factors involved in the
      control of intestinal UGT2B expression. The demonstration that Cdx2 and HNF1alpha
      are important regulators of UGT2B7 expression will aid in defining pathways for
      coordinate control of drug metabolism in the gastrointestinal tract.

PMID- 16788385
TI  - Three types of skin-surface thermometers: a comparison of reliability, validity,
      and responsiveness.
AB  - OBJECTIVE: To compare the reliability, validity, and responsiveness of a
      thermistor thermometer (thermistor) and two different infrared thermometers (one
      designed to measure tympanic temperature and one for skin temperature). DESIGN:
      Reliability and validity were evaluated by making two separate measurements from
      the skin at identical spots of each hand, forearm, shoulder, thigh, shin, and
      foot in 17 healthy subjects. Intramuscular temperature was recorded at the hand
      and shin sites. Test-retest reliability was calculated using intraclass
      correlation for each instrument. Pearson correlation assessed the relationship
      between the skin and intramuscular temperatures at the hand and shin sites
      (validity). Each instrument's ability to measure temperature change
      (responsiveness) was assessed by measuring skin temperatures serially from 17
      limbs of ten patients with complex regional pain syndrome undergoing intravenous
      regional sympathetic blockade. Responsiveness index values were calculated.
      RESULTS: Reliability was strong and similar for each device (intraclass
      correlation: thermistor = 0.96, tympanic = 0.96, skin = 0.97), as was validity
      (r: thermistor = 0.90, tympanic = 0.92, skin = 0.92). Responsiveness was
      marginally better for the infrared skin device (responsiveness index: skin = 4.2,
      tympanic = 3.6, thermistor = 3.6). CONCLUSIONS: For the purposes of clinical
      electrodiagnostic laboratory and other physiatry applications, the performance of
      the infrared thermometers is equal to or superior to that of the traditionally
      used thermistor. All three devices are highly reliable and valid, whereas the
      infrared skin device is slightly more responsive. Infrared thermometers have the
      advantage of being quicker to operate and more portable.

PMID- 16788386
TI  - One-year follow-up of two exercise interventions for the management of patients
      with ankylosing spondylitis: a randomized controlled trial.
AB  - OBJECTIVE: To assess the long-term effects on functional and mobility outcomes of
      two exercise interventions for the management of patients with ankylosing
      spondylitis. DESIGN: In an extended 12-mo follow-up of a randomized controlled
      trial, 40 patients who were diagnosed with ankylosing spondylitis according to
      the modified criteria of New York, allocated to control or experimental groups
      using a random numbers table, and who performed their respective exercise program
      at least three times per month, were included in this long-term study. The
      control group was treated during 15 sessions with a conventional exercise regimen
      in ankylosing spondylitis, whereas the experimental group received 15 sessions of
      exercises based on the treatment of the shortened muscle chains following the
      guidelines described by the Global Posture Reeducation method. These patients
      were followed up and assessed again 1 yr after entering the study, re-applying
      the same validated indexes: BASMI (Bath Ankylosing Spondylitis Metrology Index
      [tragus to wall distance, modified Schober test, cervical rotation, lumbar side
      flexion, and intermalleolar distance]), BASDAI (Bath Ankylosing Spondylitis
      Disease Activity Index), and BASFI (Bath Ankylosing Spondylitis Functional
      Index). RESULTS: The intragroup comparison between follow-up and post
      intervention data showed that both groups decrease their clinical and functional
      measures during the follow-up period. This decrease was only significant for
      lumbar side flexion and intermalleolar distance measurements, being more
      significant in the control group (P = 0.001 and P = 0.002, respectively).
      Intragroup differences between follow-up and pre-intervention assessments
      revealed that improvements in all mobility measures of the BASMI index and in the
      BASFI index were partially maintained at the 12-mo follow-up in the experimental
      group but not in the control group. The intergroup comparison (unpaired t test
      analysis) between changes on each outcome during the long-term follow-up (post
      follow-up; and pre-follow-up) showed no significant differences in the decrease
      between post-intervention and follow-up data between the study groups. On the
      other hand, the intergroup comparison between pre-intervention and follow-up data
      revealed significant differences in almost all mobility measures of the BASMI
      index (except for cervical rotation) and in the BASFI index, in favor of the
      experimental group. CONCLUSIONS: An exercise regimen based on the Global Posture
      Reeducation method and focusing on specific strengthening and flexibility
      exercises of the shortened muscle chains offers promising short- and long-term
      results in the management of patients who have ankylosing spondylitis.

PMID- 16788383
TI  - Functional properties of an alternative, tissue-specific promoter for human
      arylamine N-acetyltransferase 1.
AB  - Variable expression of human arylamine N-acetyltransferase 1 (NAT1) due to
      genetic polymorphism, gene regulation or environmental influences is associated
      with individual susceptibility to various cancers. Recent studies of NAT1
      transcription showed that most mRNAs originate at a promoter, P1, located 11.8 kb
      upstream of the single open reading frame (ORF) exon. We have now characterized
      an alternative NAT1 promoter lying 51.5 kb upstream of the NAT1 ORF. In the
      present study, analysis of human RNAs representing 27 tissue types by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and quantitative RT-PCR showed
      the upstream 51.5 kb promoter, designated P3, to be most active in specific
      tissues, including kidney, liver, lung, and trachea. All NAT1 P3 mRNAs included
      5'-untranslated region (5'-UTR) internal exons of 61 and 175 nucleotides in
      addition to the 79 nucleotide 5'-UTR exon present in P1 mRNA. CAP-dependent
      amplification of 5'-P3 mRNA termini defined an 84 bp transcription start region
      in which most start sites are centrally clustered. The hepatoma-derived HepG2
      cell line expressed a high level of P3 mRNA with the same spliced structure and
      start site pattern as found in normal tissues. A 435-bp minimal promoter was
      defined by transfection of HepG2 with luciferase expression constructs containing
      genomic fragments from the P3 start region. These findings imply a fundamental
      role for P3 in NAT1 regulation and define additional regions for genetic
      polymorphisms associated with enhanced cancer risk.

PMID- 16788387
TI  - Rehabilitation outcomes in patients with brain tumors and acute stroke:
      comparative study of inpatient rehabilitation.
AB  - OBJECTIVES: To investigate functional outcomes after hospital rehabilitation of
      patients surviving craniotomy for primary brain tumor excision compared with post
      stroke patients. DESIGN: The database of the Neurological Rehabilitation
      Department "C" of Loewenstein Rehabilitation Center was used to investigate
      primary brain tumors and first ischemic and hemorrhagic stroke patients admitted
      for hospital rehabilitation during an 11-yr period, between January 1993 and
      August 2004. Particular attention was paid to age and sex distribution, onset-to
      admission interval, length of stay, functional status at admission and discharge,
      functional gain (DeltaFI change) as measured by the FIM instrument. RESULTS: A
      total of 168 patients with craniotomy for primary brain tumor excision (128
      intracranial meningiomas and 40 cerebral gliomas) and 1660 first-stroke patients
      were admitted to the department for rehabilitation during the study period. Mean
      patient age was 59.9 yrs in meningioma group, 54.1 yrs in the glioma group, and
      60.4 yrs in the stroke group. In the meningioma and stroke groups, male patients
      were in the majority (62 and 70%); in the glioma group, there was equal sex
      distribution. On average, patients were admitted to rehabilitation treatment 13
      days after meningioma excision, 34 days after glioma operation, and 21.6 days
      after stroke. Functional variables during inpatient rehabilitation were found to
      be similar in the all groups. Average FIM rating at admission was 80.07 in the
      meningioma group, 68.2 in the glioma group, and 70.4 in the stroke group. Average
      discharge FIM rating was 90.3 for patients with meningiomas, 80.7 for patients
      with gliomas, and 87.8 for stroke patients. Functional gain was 17.9 for
      meningioma patients, 17.2 for glioma patients, and 21.8 for stroke patients.
      Average length of stay was 24 days for the meningioma group, 23 days for the
      glioma group, and 75.4 days for stroke patients; 88.1% of stroke patients, 91.7%
      of meningioma patients, and 82.7% of glioma patients were discharged to their
      homes, and 5.4, 3.4, and 8.6%, respectively, were discharged to nursing homes.
      CONCLUSIONS: Patients with brain tumors can achieve good functional outcomes with
      a shorter length of stay.

PMID- 16788388
TI  - Assessment of long-term physical function in acute respiratory distress syndrome
      (ARDS) patients: comparison of the Charlson Comorbidity Index and the Functional
      Comorbidity Index.
AB  - OBJECTIVE: It is often important to adjust for the effect of comorbid diseases on
      patient outcomes. This study compares the association between physical function
      in acute respiratory distress syndrome patients with scores on two comorbidity
      indices, the Charlson Comorbidity Index, designed to predict mortality, and the
      Functional Comorbidity Index (FCI), which was designed to predict physical
      function. DESIGN: This is a prospective, longitudinal, observational study. A
      total of 73 survivors of acute respiratory distress syndrome were contacted at 3,
      6, and 12 mos. Patient comorbidity was evaluated with the Charlson Comorbidity
      Index and the FCI. Physical function was measured using the Medical Outcomes
      Study 36-Item Short Form Health Survey Physical Function Subscale and the
      Physical Component Subscale scores. RESULT: Mean FCI and Charlson Comorbidity
      Index scores correlated fairly strongly (Spearman rho = 0.62, P < 0.001). FCI,
      but not the Charlson Comorbidity Index, scores correlated with the Physical
      Function Subscale and Physical Component Subscale scores. After controlling for
      other potentially confounding variables such as age and severity of illness
      through regression analysis, the FCI score was still significantly associated
      with both Physical Function Subscale and Physical Component Subscale scores.
      CONCLUSIONS: The FCI is a better method of measuring comorbidity with physical
      function as the outcome. This study illustrates the importance of choosing the
      most appropriate comorbidity index for the outcome of interest.

PMID- 16788389
TI  - Improving knowledge and skills for use of medication by patients after stroke:
      evaluation of a nursing intervention.
AB  - OBJECTIVE: The objective of this study was to determine if a tailored nursing
      intervention, as opposed to usual rehabilitation care, can improve knowledge and
      behavioral skills for correct use of medication use in aged stroke patients.
      DESIGN: Stratified random sampling created two homogenous groups: 73 intervention
      patients, who were provided with the nursing intervention program along with
      usual rehabilitation care, and 82 controls, who underwent usual rehabilitation
      care alone. Participants were assessed within the first week of admission to the
      rehabilitation ward, 3 mos after stroke (at the end of the intervention), and 6
      mos after stroke. An assessment instrument measuring correct knowledge and skills
      concerning medications was used. RESULTS: After 3 and 6 mos, intervention
      subjects were significantly better than controls in knowledge of shape and dosage
      of their medications, in knowledge of side effects and correct response to side
      effects, and in adherence to their dietary regimen. However, for knowledge of
      color and daily schedule of medications, there were differences at 3 mos, but
      differences were diminished after 6 mos. CONCLUSIONS: This nursing intervention,
      tailored to the specific needs of the aged stroke patient, increased the
      patients' knowledge and skills concerning medication therapy, but to a limited
      extent and for a limited time.

PMID- 16788390
TI  - Magnetic stimulation of the quadriceps femoris muscle: comparison of pain with
      electrical stimulation.
AB  - OBJECTIVE: The objective of this study was to compare pain induced by magnetic
      stimulation of the quadriceps femoris (QF) muscle with that induced by
      transcutaneous neuromuscular electrical stimulation (NMES). DESIGN: Magnetic
      stimulation and transcutaneous NMES were applied to QF muscles of 17 normal
      volunteers. The intensity of each mode of stimulation was increased in a stepwise
      manner. Peak torque values of isometric contractions of QF muscles and visual
      analog scale (VAS) scores were recorded at each intensity level. The VAS scores
      of the two stimulating modalities were compared at the intensity-generating same
      peak torque values. RESULTS: The median VAS scores for electrical and magnetic
      stimulation were 5.7 and 0.3, respectively. The median difference between the VAS
      scores for electrical and magnetic stimulation was 3.7 (range, 1.7-8.5). The mean
      of the maximum peak torque obtained from each subject was higher in magnetic
      stimulation than in electrical stimulation (9.5 +/- 4.8 vs. 4.4 +/- 2.9 Nm).
      CONCLUSIONS: Magnetic stimulation of the QF muscle produced less pain at the same
      level of isometric peak torque than did transcutaneous NMES. Magnetic stimulation
      is a potential alternative to transcutaneous NMES, especially for persons with
      intact or residual sensory function.

PMID- 16788391
TI  - Effects of botulinum toxin-A on gait velocity, step length, and base of support
      of patients with dynamic equinovarus foot.
AB  - OBJECTIVE: The aim of this study was to identify if botulinum toxin type A is a
      drug able to modify walking velocity, step length, and width of the base of
      support of adult patients with dynamic equinovarus foot deformity resulting from
      upper motor neuron syndrome. DESIGN: This retrospective study analyzed data from
      20 patients' files selected from 448 consecutive charts. The main inclusion
      criteria were the presence of dynamic equinovarus foot deformity due to upper
      motor neuron syndrome, age between 20 and 80 yrs, evaluation of temporospatial
      parameters of gait by the Gait Mat II before and 4 wks after botulinum toxin type
      A injection to the calf muscles, and the ability to walk barefoot, unassisted,
      and without braces. For data analysis, based on walking velocity, we divided the
      patients into two groups, slow walking velocity (0.18-0.49 m/sec) and medium
      walking velocity (0.50-0.99 m/sec). RESULTS: Width of the base of support was
      significantly reduced after botulinum toxin type A treatment, both for the
      affected (P < 0.005) and the unaffected limbs (P < 0.002), in the group of
      subjects walking at medium velocity. Walking velocity or step length of either
      group of patients was not significantly modified by botulinum toxin type A
      treatment. CONCLUSIONS: Based on this study, a significant effect of botulinum
      toxin type A on width of the base of support is evident and seems to be the
      result of a better position of the affected foot during the stance phase of
      locomotion leading to increased body stability and consequent reduction of width
      of the base of support of the unaffected limb. No change was evident in step
      length or walking velocity for this patient population.

PMID- 16788392
TI  - Aerobic fitness in women with chronic discogenic nonradicular low back pain.
AB  - OBJECTIVE: The purpose of this study was to determine if aerobic fitness varies
      between women with and without chronic discogenic non-radicular low back pain.
      DESIGN: Prospective cross-sectional descriptive study. RESULTS: : Analysis of
      variance revealed that maximal oxygen consumption was lower (P = 0.05) in women
      with low back pain compared with the control group. In addition, there was a
      significant reduction (P = 0.05) in reported exercise training duration and
      frequency but no change in exercise intensity (P = 0.1) in the study group after
      the onset of low back pain. The low back pain group had minimal disability (19%)
      based on the Oswestry Disability Questionnaire. CONCLUSIONS: Women with chronic
      discogenic non-radicular low back pain have lower maximal oxygen consumption than
      age-matched controls. However, this study group continued to exercise safely at
      the same exercise training intensity as before their low back pain and had
      minimal disability and above-average aerobic fitness.

PMID- 16788393
TI  - High-frequency cranial electrostimulation (CES) in patients with probable
      Alzheimer's disease.
AB  - In a previous study, low-frequency cranial electrostimulation did not improve
      cognition and (affective) behavior in patients with probable Alzheimer's disease.
      In the present study, 21 Alzheimer's disease patients, divided into an
      experimental (n = 11) and a control group (n = 10), were treated for 30 mins/day,
      5 days/wk, for 6 wks with high-frequency cranial electrostimulation. Similar to
      the previous study, no improvements on cognition and (affective) behavior were
      found.

PMID- 16788394
TI  - Characteristics and treatment of headache after traumatic brain injury: a focused
      review.
AB  - Headache is one of the most common complaints in patients with traumatic brain
      injury. By definition, headache that develops within 1 wk after head trauma (or
      within 1 wk after regaining consciousness) is referred to as posttraumatic
      headache (PTH). Although most PTH resolves within 6-12 mos after injury,
      approximately 18-33% of PTH persists beyond 1 yr. We performed a systematic
      literature review on this topic and found that many patients with PTH had
      clinical presentations very similar to tension-type headache (37% of all PTH) and
      migraine (29% of all PTH). Although there is no universally accepted protocol for
      treating PTH, many clinicians treat PTH as if they were managing primary
      headache. As a result of the heterogeneity in the terminology and paucity in
      prospective, well-controlled studies in this field, there is a definite need for
      conducting double-blind, placebo-controlled treatment trials in patients with
      PTH.

PMID- 16788396
TI  - Re: Cadaveric study of methods for subscapularis muscle needle insertion.

PMID- 16788397
TI  - Atrophy and clinical weakness of the iliopsoas muscle: a manifestation of hip
      osteoarthritis.

PMID- 16788398
TI  - An altruistic approach to clinical trials: the National Clinical Trials
      Consortium (NCTC).

PMID- 16788399
TI  - Resident selection: a key to the future of orthopaedics.
AB  - Recognizing the challenges presented in the process of resident selection, in
      1981 the American Orthopaedic Association formed a Steering Committee on Resident
      Selection. This Committee was charged with studying the processes involved in the
      selection of orthopaedic residents and developing guidelines and making
      suggestions to program directors. The activities of the Committee focused on five
      areas: (1) the mechanics of resident selection; (2) the assessment of cognitive
      skills; (3) the assessment of motor ability; (4) the assessment of noncognitive
      factors (the affective domain); (5) the assessment of "dropouts." The Committee
      made the following recommendations to help program directors in the selection of
      residents: (1) use of a standardized application form; (2) full disclosure to
      applicants; (3) careful selection of candidates to be interviewed; (4) careful
      planning and implementation of the interview and visit; (5) broad faculty
      representation and discussion at time of selection; (6) due diligence when
      necessary. We still believe these criteria important in resident selection.

PMID- 16788400
TI  - Orthopaedic trauma fellowships.

PMID- 16788401
TI  - Spontaneous regression of steroid-related osteonecrosis of the knee.
AB  - It is unknown whether lesions of steroid-related osteonecrosis of the knee
      increase or decrease in size during the course of the disease after diagnosis. We
      sought to determine whether steroid-related osteonecrosis of the knee would have
      spontaneous changes in size, and if so, the factors affecting the change. We
      performed baseline and followup (minimum of 1 year) magnetic resonance imaging
      scans on 30 knees of 17 patients. We then used image registration techniques to
      match two sets of images. Lesion size change was evaluated on all contiguous
      pairs of matched magnetic resonance images. Fourteen Stage 1 (preradiographic
      stage) knees in seven patients showed spontaneous incomplete regression without
      subsequent collapse. These patients had early steroid-related lesions detected
      within 3 years after starting steroid treatment and all showed bilateral and
      multifocal involvement; lesion regression occurred regardless of location. The
      initial size and location of the lesions and discontinuing steroid administration
      did not seem to affect regression. Regression can occur in some patients with
      early steroid-related osteonecrosis of the knee, and the time between initiation
      of steroid treatment and its diagnosis might be the most significant predictive
      factor.

PMID- 16788402
TI  - A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury.
AB  - Collagen synthesis inhibition potentially can reduce adhesion formation after
      tendon injury but also may affect cutaneous wound healing. We hypothesized that a
      novel orally administered collagen synthesis inhibitor (CPHI-I) would
      substantially reduce flexor tendon adhesions after injury, without any clinically
      important effect on cutaneous wound healing. The experiments were performed in a
      rat model with an in-continuity crush injury model in the rat hindfoot flexor
      tendon to provoke adhesion formation. Assays of dermal collagen production and
      the rate of healing of an excised wound were performed to assess cutaneous wound
      healing. Animals in the treatment groups received CPHI-I for 1, 2, or 6 weeks and
      were assessed at either 2 or 6 weeks. The work of flexion in the injured digit
      was reduced in the CPHI-I-treated animals compared with control animals, (0.188 J
      versus 0.0307 J at 2 weeks, and 0.0231 J versus 0.0331 J at 6 weeks) The
      cutaneous wound healing rate was similar in all animals, but dermal collagen
      synthesis was reduced in the treated animals. The CPHI-I seems to reduce tendon
      adhesion, and although collagen synthesis was reduced in cutaneous wounds, CPHI-I
      did not retard wound healing.

PMID- 16788403
TI  - Hand fellowships.

PMID- 16788404
TI  - ABMS' Maintenance of Certification: the challenge of continuing competence.
AB  - The American Board of Medical Specialties, since its inception in 1933 as the
      Advisory Board for Medical Specialties, is concerned with the education, training
      and certification of physician specialists. Although not perfect, the initial
      certification process is quite good and accomplishes its intended purpose.
      However, initial certification is based on a primarily knowledge-based
      "snapshot." The newly developed Maintenance of Certification Program will
      evaluate the competencies, medical knowledge, patient care, interpersonal and
      communication skills, professionalism, practice-based learning and improvement
      and systems-based practices believed to be necessary and sufficient for certified
      physicians to have and maintain throughout their entire professional career.
      Furthermore, the process will focus on education and assessment to encourage
      continuous quality improvement in clinical practice.

PMID- 16788405
TI  - The need for research training in orthopaedic residency education.
AB  - Orthopaedic surgery residents should be exposed during their clinical training to
      the processes of creativity and innovation that are the basis of research. The
      definition of a research experience for surgery residents should be broad and
      include not only traditional bench research in a basic science environment but
      also translational and clinical research to move innovation from bench to bedside
      and validate its value in a scientific manner. Additionally, there are enormous
      opportunities for surgeons to study healthcare delivery and policy and to develop
      new approaches to educating colleagues, other medical personnel, and patients.
      The question that must be addressed is how can the knowledge and human resources
      residing in orthopaedic surgery best be used to meet the challenges future
      residents will face as healthcare undergoes profound changes? How these issues
      are managed in a rapidly changing environment is the critical issue and the
      challenge faced by surgical training programs wishing to remain viable and
      provide trainees with the opportunity to adapt and be successful in the future.
      What is state of the art today will not be tomorrow and unless trainees are
      encouraged and taught to be creative and innovative they risk becoming surgical
      dinosaurs.

PMID- 16788406
TI  - Subacromial space measurement: a reliable method indicating fatty infiltration in
      patients with rheumatoid arthritis.
AB  - Proximal migration of the humeral head is thought to indicate fatty infiltration
      of the rotator cuff muscles or rotator cuff tears. We sought to evaluate the
      influence of these rotator cuff abnormalities on the subacromial space. Using
      anteroposterior radiographs, ultrasound, and computed tomography, we analyzed 54
      shoulders in 29 patients with rheumatoid arthritis. The upward migration index
      was defined as proximal migration of the humeral head relative to its size. The
      mean muscle density from computed tomography images was used to indicate fatty
      infiltration. Fatty infiltration of the infraspinatus muscle showed the strongest
      correlation with proximal migration. After correcting for age, cuff tears, and
      rheumatoid disease, the partial correlation coefficient between both remained
      strong. A subdivision in proximal migration is proposed to screen for rotator
      cuff abnormalities. A large amount of fatty infiltration was indicated by an
      upward migration index less than 1.25, a medium amount by an upward migration
      index between 1.25 to 1.35, and a small amount by an upward migration index
      greater than 1.35. Measurement of proximal migration using the upward migration
      index provides a reliable screening method indicating fatty infiltration of the
      rotator cuff.

PMID- 16788407
TI  - Transsciatic foramen pedicle VRAM coverage of gluteal defects.
AB  - Tumors of the gluteal region are rare. Defects from resection often can be closed
      primarily. Some patients require local flaps such as a gluteus maximus V-Y
      advancement flap. Such flaps typically result in some muscle dysfunction. In
      addition, the use of local irradiated tissue may lead to wound complications and
      prolonged hospitalization. Avoiding local radiated tissue, such as the gluteal
      muscles, can be beneficial. We report our experience using a novel route by
      passage through the transsciatic foramen to transpose a pedicle vertical rectus
      abdominis myocutaneous flap. This regional option avoids gluteal muscle
      dysfunction and potential wound complication from irradiated tissue.

PMID- 16788409
TI  - Research fellowships.

PMID- 16788408
TI  - Treatment of the complex idiopathic clubfoot.
AB  - Treatment with the Ponseti method corrects congenital idiopathic clubfeet in the
      majority of patients. However, some feet do not respond to the standard treatment
      protocol. We describe the characteristics and treatment results of these complex
      idiopathic clubfeet. We identified 50 patients (75 clubfeet) from 762 consecutive
      patients treated at five institutions. Clinically, complex clubfeet were defined
      as having rigid equinus, severe plantar flexion of all metatarsals, a deep crease
      above the heel, a transverse crease in the sole of the foot, and a short and
      hyperextended first toe. The Achilles' tendon was exceptionally tight and
      fibrotic up to the middle of the calf. Correction was achieved in all patients by
      modifying the Ponseti manipulation and casting technique. Correction required an
      average of five casts (range, 1-10 casts). Two patients (4%) not initially
      recognized as having complex clubfeet had a posterior release with tendo Achillis
      lengthening. There were seven relapses that responded to casting. Three patients
      had a second tenotomy. Modifying the treatment protocol for complex clubfeet
      successfully corrected the deformity without the need for extensive corrective
      surgery.

PMID- 16788410
TI  - Interview, Dean's Letter, and Affective Domain Issues.
AB  - The evaluation of medical students consists, in part, of a transparent academic
      record of grades, awards, and any publications or special clinical activities. In
      addition, however, each student is evaluated through more opaque processes within
      a medical school that speak to the behavior, character, and developing
      professionalism observed throughout the 4 year curriculum. In the process of
      choosing a medical student for residency, these non-academic factors may play a
      significant role in determining the best match between student and program. Three
      aspects of the non-academic record of the student are presented: the Interview;
      the Dean's Letter; and other Affective Domain Issues showing the lack of
      systematic study of these variables and the degree of difficulty in ferreting out
      information germane to the residency selection process. Nevertheless, information
      can be gleaned from careful interviewing and examination of information provided
      by the medical school to more fully assess each student. The most challenging
      task is to distinguish between behavior associated with the process of maturation
      and that associated with significant psychopathology.

PMID- 16788411
TI  - Patellofemoral pain syndrome: validity of clinical and radiological features.
AB  - Data regarding validity of clinical and radiographic findings in diagnosing
      patellofemoral pain syndrome are inconclusive. We prospectively assessed how
      sensitive and specific key patellofemoral physical examination tests are, and
      evaluated the prevalence of physical examination and radiographic findings. Sixty
      one infantry soldiers with patellofemoral pain syndrome and 25 control subjects
      were evaluated. The sensitivity of the patellar tilt, active instability, patella
      alta, and apprehension tests was low (less than 50%); specificity ranged between
      72% and 100%. Although the prevalence of positive patellar tilt and active
      instability tests was significantly greater in subjects with patellofemoral pain
      syndrome, there were no significant differences between the groups in the results
      of the other two tests. Soldiers with patellofemoral pain syndrome presented with
      increased quadriceps angle, lateral and medial retinacular tenderness,
      patellofemoral crepitation, squinting patella, and reduced mobility of the
      patella. There were no differences between the groups in the prevalence of lower
      limb and foot posture alignment and knee effusion. Plain radiography showed
      increased patellar subluxation in soldiers with patellofemoral pain syndrome.
      Other radiographic measures (sulcus angle, Laurin angle, Merchant angle, and
      Insall-Salvati index) were similar in both groups. We provide evidence regarding
      the validity of clinical and radiographic features commonly used for diagnosing
      patellofemoral pain syndrome. Physical examinations were more useful than plain
      radiography.

PMID- 16788412
TI  - Influence of cryosurgery on treatment outcome of low-grade chondrosarcoma.
AB  - Successfully managing low-grade chondrosarcomas with margins considered less than
      wide would minimize the need for extensive reconstruction. We report our
      experience using cryotherapy as an adjuvant to treat patients with low-grade
      intracompartmental chondrosarcomas. Ten consecutive patients had intralesional
      resections including curettage, cryo-surgery, and polymethylmethacrylate
      application. Eight of these patients required prophylactic skeletal
      stabilization. We retrospectively reviewed the outcomes for tumor recurrence,
      disease progression, and complications. The Musculo-skeletal Tumor Society rating
      scale was used to evaluate functional outcome, and the mean score was 27 points
      (range, 25-30 points). The mean age of the patients was 54.4 years (range, 29-83
      years), and the average followup was 38.5 months (range, 24-60 months). Patients
      were treated for lesions of the femur (n = 3), humerus (n = 3), scapula (n = 2),
      tibia (n = 1), and acetabulum (n = 1). There was no evidence of recurrence or
      metastases. At the latest followup, all patients were well, however, one patient
      had hardware loosening. In this small group of patients, intralesional resection
      with adjuvant cryoablation provided an alternative to more radical procedures for
      low-grade intracompartmental chondrosarcoma.

PMID- 16788413
TI  - Giant cell reparative granuloma of the temporal bone treated with calcitonin.
AB  - OBJECTIVE: A case report of a giant cell reparative granuloma involving the
      temporal bone successfully treated with calcitonin. STUDY DESIGN: Case report.
      SETTING: Teaching hospital, tertiary referral center. PATIENT, INTERVENTION, AND
      RESULTS: A 62-year-old man was referred to the otolaryngology department with an
      extensive temporal bone lesion confirmed by biopsy to be a giant cell reparative
      granuloma. As an alternative to surgery, calcitonin therapy was commenced. After
      12 months of treatment, clinical and audiological parameters had returned to
      normal, and radiological appearances had shown significant bony remodeling. These
      parameters remain stable 24 months after cessation of treatment. CONCLUSION:
      Calcitonin is a safe and economical medical treatment, which should be considered
      for destructive giant cell granulomas of the temporal bone.

PMID- 16788414
TI  - Factors relating to the vertigo control and hearing changes following
      intratympanic gentamicin for intractable Meniere's disease.
AB  - OBJECTIVE: To look for factors relating to the vertigo control and hearing
      changes after intratympanic injections of gentamicin (GM). STUDY DESIGN:
      Prospective. SETTING: Tertiary referral medical center. PATIENTS: Twenty-eight
      patients with intractable Meniere's disease. INTERVENTIONS: Three intratympanic
      injections of GM (once per day for three consecutive days). MAIN OUTCOME
      MEASURES: Although five patients needed further GM injections or vestibular
      neurectomy because of poor control (Group I), 23 patients had their vertigo
      controlled for more than two years without further treatment (Group II). The
      number of vertigo spells per month, pure-tone audiometry, electrocochleography,
      caloric response, post-head shake nystagmus, and plasma vasopressin as a stress
      marker were examined. RESULTS: Before GM injections, there was no difference in
      the number of vertigo spells per month between Groups I and II. However, the
      hearing thresholds were higher in Group I. Hearing improvement, increase in
      percentage of canal paresis and induction of post-head shake nystagmus were
      observed after GM injections only in Group II. Even in the 11 patients who showed
      an improvement in hearing of more than 10 dB (hearing improvement group),
      percentage of canal paresis was increased after GM. More, premedication plasma
      vasopressin levels were lower in the hearing improvement group as compared with
      the hearing loss/no changes group. Four of eight patients became negative for
      dominant negative summating potential in electrocochleography after GM injections
      in the hearing improvement group. CONCLUSION: Our data indicate that the
      frequency of vertigo is not a key factor in the vertigo control after GM
      injections, that induction of vestibular damage in the injected ear is essential
      for the control of vertigo and this effect is mostly pronounced in patients with
      milder hearing loss, and that hearing improvement is not only a consequence of
      good vertigo control but also affected by the stress level before treatment.

PMID- 16788415
TI  - The anti-oxidant effect of alpha-tocopherol in the prevention of experimentally
      induced myringosclerosis.
AB  - HYPOTHESIS: The objective of this study was to investigate the possible effect of
      alpha-tocopherol on the prevention of experimentally induced myringosclerosis.
      BACKGROUND: Myringosclerosis is a common sequela of ventilation tube treatment of
      otitis media with effusion. The relationship between oxygen-derived free radicals
      and occurrence of myringosclerosis has been proven in experimental models, and it
      was also shown that the formation of myringosclerosis after experimental
      myringotomy could be reduced by application of various free radical scavengers.
      METHODS: Eighteen Wistar albino rats were myringotomized on the left side and
      randomly separated into two groups: group A consisted of rats which received
      intramuscular alpha-tocopherol injections 100 mg/kg daily and group B which were
      injected with physiological serum only. The occurrence of myringosclerotic
      plaques in the tympanic membranes of the two groups was compared by
      otomicroscopy, histopathology, and tympanometry, which is a novel method of
      quantification. Blood samples were collected for biochemical evaluation, and the
      tympanic membranes were harvested on the 15th day of the experiment. RESULTS: In
      otomicroscopic evaluation, tympanic membranes in group B revealed varying degrees
      of myringosclerotic plaques; on the other hand, tympanic membranes in group A
      showed faint or no existence of myringosclerosis. The mean malondialdehyde levels
      were 1.33 +/- 0.11 micromol/L in group A and 7.49 +/- 1.37 micromol/L in group B
      (Z = -1.906, p = 0.057). In all ears from group B, the magnitude of the maximum
      admittance measured by tympanometry reduced to approximately 40% of the values
      obtained from group A (Z = -2,160, p = 0.031). The mean magnitude of the maximum
      admittance from group A was very close to the standardization values of Wistar
      albino rats, which predicts a functional outcome. CONCLUSION: The formation of
      myringosclerosis after experimental myringotomy can be diminished by
      intramuscular alpha-tocopherol injections.

PMID- 16788416
TI  - Surgical results of cochlear implantation in malformed cochlea.
AB  - OBJECTIVE: To report the surgical aspects of cochlear implantation in malformed
      cochlea. SETTING: Tertiary care center. STUDY DESIGN: Retrospective case review.
      METHODS: Between November 1997 and October 2004, 20 patients with inner ear
      malformations were implanted in our department. The age range was between 2 and
      37 years (average, 8.8 yr). The anomalies were classified according to Sennaroglu
      and Saatci classification. There were two patients with common cavity deformity,
      four cases of incomplete partition (IP) type I (cystic cochleovestibular
      malformation), four cases of IP type II (classical Mondini's deformity), nine
      patients with large vestibular aqueduct (LVA) syndrome, and one patient with X
      linked deafness. RESULTS: Standard transmastoid facial recess approach was used
      in 17 patients (three patients with IP I, four patients with IP II, and nine
      patients with LVA syndrome). In the remaining patient with IP I, because of the
      dehiscent and anteriorly located facial nerve, the surgical approach had to be
      modified, and an anteroposterior approach was used. After elevating the
      tympanomeatal flap, the electrode was inserted through the ear canal and then
      transferred to the mastoid through a full-length cut produced in the ear canal.
      The flap then returned to its place. In the patients with common cavity
      deformity, the electrode was inserted by the transmastoid labyrinthotomy
      approach. Facial nerve had an abnormal course in four patients, but no patient
      had facial weakness postoperatively. Cerebrospinal fluid gusher was encountered
      in four patients, whereas oozing was present in five patients. It seems that a
      slightly larger cochleostomy may reduce postoperative rhinorrhea. The patient
      with common cavity deformity showed abnormal vestibular stimulation which
      decreased and was totally abolished during a 3-month period. CONCLUSION: Based on
      these findings, cochlear implantation is surgically feasible in patients with
      common cavity, IP types I and II, and LVA. The surgeon should be ready to make
      modifications in the surgical approach because of the abnormal course of the
      facial nerve and be ready to produce special precautions to cerebrospinal fluid
      gusher.

PMID- 16788417
TI  - Progressive sensorineural hearing impairment in maternally inherited diabetes
      mellitus and deafness (MIDD).
AB  - OBJECTIVE: To study the progression of hearing impairment (HI) and audiological
      features in patients with the mitochondrial A to G mutation in the tRNA(LEU(RUU))
      gene at position 3,243 associated with maternally inherited diabetes and
      deafness. DESIGN: Retrospective phenotype genotype family study. SETTING:
      Tertiary referral center. PATIENTS: Six adult family members with the
      mitochondrial tRNA(LEU(RUU)) gene mutation at location 3,243. Data were obtained
      on medical history, otological examination, and pure tone and speech audiometry.
      Peripheral leukocytes were analyzed for the presence of the mutation, and
      heteroplasmy levels were determined. Selected patients underwent vestibular
      testing, brainstem-evoked response audiometry and neurological examination.
      RESULTS: One patient showed relatively normal hearing, whereas in the others, HI
      had started at 27 to 79 years of age. All the patients showed progression in HI
      of approximately 1.4 dB/yr on average at 0.25 and 8 kHz. In the frequency range
      0.5 to 2 kHz, progression was approximately 2 dB/yr; at 4 kHz, progression was
      2.4 dB/yr. Vestibular and brainstem-evoked response audiometry test results were
      normal. All the patients achieved the maximum speech recognition score, as was
      expected based on their pure-tone average at 1, 2, and 4 kHz. CONCLUSION: Our six
      adult patients with the mitochondrial tRNA(LEU(RUU)) gene mutation at location
      3,243 showed almost normal to severe HI which was progressive beyond
      presbyacusis. Data from the literature and our findings suggest a cochlear
      localization of the HI.

PMID- 16788418
TI  - Comparison of intratympanic and intravenous dexamethasone treatment on sudden
      sensorineural hearing loss with diabetes.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of
      intratympanic administration of dexamethasone (IT-DEX) treatment on sudden
      sensorineural hearing loss (SSNHL) patients with diabetes by comparing the
      results with intravenous administration of dexamethasone (IV-DEX) treatment.
      STUDY DESIGN: Comparative study. SETTING: University hospital and affiliated
      hospital. PATIENTS: Ten sequential SSNHL patients with diabetes receiving IT-DEX
      and 21 sequential SSNHL patients with diabetes receiving IV-DEX. Patients with
      low tone hearing loss were excluded. INTERVENTION: In the IT-DEX group, two
      methods were applied to deliver DEX (4 mg/ml): injection through a perforation
      made by laser-assisted myringotomy or through a tympanostomy tube. IT-DEX
      administration was performed on 8 sequential days. In the IV-DEX group, DEX was
      administrated intravenously starting from an amount of 8 mg/d followed by taped
      doses for 10 days. MAIN OUTCOME MEASURES: Preprocedure and postprocedure hearing
      levels and complications. RESULTS: In the IT-DEX group, the average hearing level
      before the treatment was 79 dB. Overall, all 10 patients showed improvement of
      more than 10 dB in the pure-tone audiogram, with a mean improvement of 41 dB.
      Seven patients (70%) demonstrated successful results, and four recovered
      completely. In the IV-DEX group, 14 (67%) of the 21 patients showed improvement
      of more than 10 dB with a mean improvement of 25 dB. Thirteen patients (62%)
      demonstrated successful results. Free blood sugar during and after the IT-DEX
      treatment remained below the pretreatment levels, whereas four patients in the IV
      DEX group demonstrated worsening of the hyperglycemia. CONCLUSION: IT-DEX
      treatment is at least as effective as IV-DEX treatment for SSNHL patients with
      diabetes.

PMID- 16788419
TI  - Cartilage tympanoplasty for management of tympanic membrane atelectasis: is
      ventilatory tube necessary?
AB  - OBJECTIVES: Cartilage/perichondrium composite graft with concomitant placement of
      a ventilation tube is a common practice among otologists to reverse atelectasis
      and to repneumatize the middle ear. We conducted this study to investigate the
      necessity of a ventilation tube primarily incorporated into the
      perichondrium/cartilage graft for reconstruction of the atelectatic tympanic
      membrane (TM). STUDY DESIGN: Prospective clinical trial. METHODS: Forty-six
      patients with TM atelectasis and intact ossicular chain were randomized to 2
      groups. In Group I, 23 patients underwent reconstruction of the TM with
      perichondrium/cartilage graft and intraoperative T-tube insertion and in Group
      II, 23 patients underwent reconstruction of the TM with perichondrium/cartilage
      graft without ventilation tube insertion. Outcome measures were as follows: graft
      success, improvement of hearing, and postoperative complications. Analysis of the
      results was performed by Student's paired t test. The level of significance was
      set at 5%. RESULTS: Significant postoperative improvement of pure-tone air
      conduction threshold averages and air-bone gap averages were reported in the 2
      studied groups (p < 0.001). The postoperative air-bone gap averages showed no
      statistically significant difference between Groups I and II (p > 0.05).
      Conductive hearing loss requiring revision developed in 2 patients (8.69%) in
      Group I and in 3 patients (13%) in Group II. CONCLUSION: In the atelectatic ear,
      cartilage allowed reconstruction of the TM with good anatomical and functional
      results. Primary insertion of a ventilation tube into the graft is not necessary.

PMID- 16788420
TI  - Impact of multiple etiology on dizziness handicap.
AB  - OBJECTIVE: Our aim was to find the ratio of multiple diagnosis in dizziness
      patients and to evaluate the effect of multiple etiologies on handicap level of
      the patient. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral
      center. INTERVENTION: The data of 703 patients (178 men and 525 women) were
      included in the study. Diagnoses of the patients were made in a multiple
      specialty environment including otolaryngology, neurology, cardiology, internal
      medicine, and rehabilitation medicine. MAIN OUTCOME MEASURES: All patients filled
      the dizziness handicap inventory and pointed the severity of dizziness on a 10
      point visual analog scale. RESULTS: Four hundred thirty-three patients (61.6%)
      have only one diagnosis, whereas 183 (26%) had two. Three diseases have been
      found in 34 patients (4.8%), and four diseases were present in eight patients
      (1.1%). The mean number of diagnosis in one patient was 1.32 +/- 0.71. There was
      a significant difference between two sexes on the number of disease. There was no
      correlation between age and the number of diagnosis. There was no significant
      difference in functional scale, but the statistically significant increases are
      present in both physical (p < 0.05) and emotional (p < 0.01) scales. There was no
      correlation between age and handicap levels. CONCLUSION: Multiple diagnoses were
      important factors on physical and emotional handicaps. It was also found that
      this problem is not limited with older age group.

PMID- 16788421
TI  - Multichannel cochlear implantation in the scala vestibuli.
AB  - OBJECTIVE: Sensorineural hearing loss resulting from otosclerosis, meningitis,
      chronic otitis media, autoimmune ear disease, and trauma can be associated with
      partial or total obstruction of the cochlear scalae. Multichannel cochlear
      implantation may be difficult in a cochlea with an obstructed scala tympani. The
      purpose of this study is to determine the safety and efficacy of scala tympani
      electrode insertion. STUDY DESIGN: Retrospective chart review. SETTING: Academic
      medical center. PATIENTS: Eight children and adults with profound sensorineural
      hearing loss who underwent cochlear implantation with known scala vestibuli
      electrode array insertion were subjects for this study. INTERVENTIONS: Eight
      study subjects underwent implantation: five with the Nucleus 24RCS (Contour)
      device and three with the Nucleus 24M device. OUTCOME MEASURES: Imaging findings,
      operative findings, and age-appropriate speech perception testing. RESULTS: All
      patients had full electrode insertion. Various obstructive patterns on computed
      tomography and magnetic resonance imaging were found, and there was a range of
      speech perception results. All but one patient improved based on age-appropriate
      monosyllabic word and sentence tests. CONCLUSION: Scala vestibuli multielectrode
      insertion is a viable alternative when scala tympani insertion is not possible
      because of abnormal anatomy or anatomical changes secondary to disease or
      previous implantation. We will also present an algorithm of options for decision
      making for implantation when encountering cochlear obstruction and difficult
      electrode insertion.

PMID- 16788422
TI  - Glutathione s-transferase gene polymorphisms in Italian patients with sudden
      sensorineural hearing loss.
AB  - HYPOTHESIS: To investigate the association between glutathione S-transferase
      (GST) gene polymorphisms and sudden sensorineural hearing loss (SSNHL) in a
      population of consecutive Italian patients. Assuming that reactive oxygen species
      formation may play a role in inner ear damage, we investigated whether profiles
      of GSTs antioxidant enzymes M1 and T1 genotypes may be associated with the risk
      of SSNHL. STUDY DESIGN: A prospective study in patients with SSNHL. PATIENTS AND
      METHODS: We investigated 80 Italian patients with SSNHL for the frequency of
      GSTT1 and GSTM1 polymorphisms. Genotype distribution of all factors found in
      patients were compared with those of 80 healthy control subjects of the same
      ethnic background using chi and odds-ratio analysis. Statistical significance was
      accepted at a level of p < 0.05. RESULTS: In our series, the frequencies of GSTM1
      and GSTT1 null genotypes did not differ from those of the control subjects.
      CONCLUSION: The few studies regarding genetic polymorphisms of GSTs in SSNHL are
      not conclusive. Further studies are needed to investigate the role of
      antioxidants including GSTs in SSNHL and to provide the lacking information to
      improve our knowledge in the field before implementing the use of genetic
      polymorphism in the SSNHL medicine daily practice.

PMID- 16788423
TI  - Long-term results in ossiculoplasty: an analysis of prognostic factors.
AB  - OBJECTIVES: The aim of the present study is to examine the prognostic factors
      based on 6-month and 5-year results of ossiculoplasty. STUDY DESIGN:
      Retrospective analysis was made on the ossiculoplasty cases in a county hospital.
      The information was extracted from a computer database. METHODS: All patients who
      had ossiculoplasty were routinely followed up in a dedicated ear audit clinic on
      a yearly basis. Between 1988 and 1999, 242 ossiculoplasties for chronic otitis
      media were performed on 197 patients. Only the first ossiculoplasty operation
      performed on each patient during the study period was included in the analysis.
      The 6-month and 5-year results were analyzed. Two different statistical methods
      were used--logistic regression analysis and the analysis of variance (ANOVA). A
      successful ossiculoplasty is defined as a postoperative air-bone gap (ABG) of 20
      dB or better. RESULTS: The overall success rate of ossiculoplasty was 66.5% at 6
      months and 50.3% at 5 years. In a multivariate analysis using logistic
      regression, those with present malleus were 6.36 times more likely to be
      successful. Using ANOVA, absent malleus and otorrhea were unfavorable factors of
      the 6-month ABG. Using logistic regression for the 5-year analysis, malleus
      remained a significant predictor at 5 years. Those with malleus were 2.65 times
      more likely to be successful. Using ANOVA, absent malleus was the only
      significant unfavorable factor of postoperative ABG at 5 years. In the univariate
      analysis, absent stapes and revision surgery are regarded as possible unfavorable
      factors. CONCLUSION: In the present study, the authors try to define the studied
      population (chronic otitis media) and the follow-up period (6 months and 5
      years), and use logistic regression and ANOVA for statistical analysis. Absent
      malleus and otorrhea are important unfavorable factors for short-term outcome in
      ossiculoplasty (6 months), whereas absent malleus is the only important
      unfavorable factor for long-term outcome in ossiculoplasty (5 years).

PMID- 16788424
TI  - Topical application of mitomycin C to the middle ear is ototoxic in the gerbil.
AB  - HYPOTHESIS: Mitomycin C is ototoxic when applied topically to the structures of
      the middle ear. BACKGROUND: Mitomycin C is a topically applied medication widely
      used in a variety of surgical procedures to prevent excessive scar tissue
      formation. Its safety for use during otologic procedures has not been fully
      evaluated. METHODS: A laboratory study was undertaken using the Mongolian gerbil
      as an animal model. Both acute and chronic effects on cochlear function of
      mitomycin C were assessed with measurements of compound action potential (CAP)
      thresholds of the auditory nerve, CAP input/output functions, distortion product
      otoacoustic emissions, and endocochlear potentials. Morphologic changes were
      assessed with light microscopy using hematoxylin-eosin staining as well as
      transmission electron microscopy. RESULTS: Five-minute applications of mitomycin
      C (0.5 mg/ml) to the entire surface of the middle ear adversely affected CAP
      thresholds, input/output functions, distortion product otoacoustic emissions, and
      the endocochlear potential. Ninety-minute exposures of mitomycin C solely to the
      round window produced similar changes. Histologic evaluation of animals 1 week
      after treatment showed damage to cochlear hair cells, the stria vascularis, and
      spiral ganglion neurons when compared with controls. CONCLUSION: Mitomycin C can
      produce substantial sensorineural hearing loss when applied topically to the
      gerbil middle ear for even brief periods. Consequently, its safety for topical
      use in the human middle ear is highly questionable.

PMID- 16788425
TI  - Dehiscent high jugular bulb: a pitfall in middle ear surgery.
AB  - OBJECTIVE: The aim of this study was to present our experience on facing the
      dehiscent high jugular bulb (HJB) during middle ear surgery in the past 2
      decades. STUDY DESIGN: Retrospective review. SETTING: Secondary referral
      hospital. PATIENTS: From January 1982 to June 2002, consecutive 1,657 patients
      underwent surgical intervention for middle ear cleft diseases, a total of 1,857
      operations. Of them, 10 ears (0.5%) in nine patients were proven to have
      dehiscent HJB during operation for adhesive otitis media in four ears and for
      chronic otitis media with cholesteatoma in six ears. MAIN OUTCOME MEASURES: Each
      patient underwent otoscopic examination, radiographic examination, and audiometry
      before and 6 months after operation. RESULTS: Otoscopic examination revealed
      atrophic changes in the pars tensa with adhering to the promontory in two ears,
      attic retraction in one ear, and both findings in seven ears. All lesions were
      located beneath the basal turn of the cochlea and the round window niche at
      anteroinferior and/or posteroinferior quadrants. Active bleeding was encountered
      in two ears (20%) while elevating the tympanomeatal flap, which was treated by
      pressure compression associated with gelfoam sheet, then covered with an
      autologous cartilage to protect the dehiscent bulb. For the remaining eight ears,
      the bulbs were reinforced with fascia, perichondrium, or autologous cartilage.
      All 10 ears were allowed completion of the planned surgery without complications.
      CONCLUSION: HJB is not a contraindication for middle ear surgery. Awareness of
      this pitfall may lessen the operation risk.

PMID- 16788426
TI  - Sac surgery results as a function of preoperative distress level.
AB  - OBJECTIVE: To evaluate the postoperative status of the patients after
      endolymphatic sac decompression (ESD) for intractable unilateral definite
      Meniere's disease (MD) using the American Academy of Otolaryngology-Head and Neck
      Surgery (AAO-HNS) 1995 criteria and to discuss the current status of ESD in the
      management of MD, especially after the wide use of intratympanic administration
      of gentamicin for the treatment of intractable MD. STUDY DESIGN: Retrospective
      questionnaire-based analysis. METHODS: Thirty-nine patients who had undergone ESD
      between 1996 and May 2003 at Sanjay Gandhi Post Graduate Institute of Medical
      Sciences, Lucknow, India, were evaluated via a set format according to AAO-HNS
      1995 guidelines. Their preoperative and postoperative data were compared.
      RESULTS: We found significant improvement in functional level scales (FLSs) in
      84.6%, Class A vertigo control in 82%, and improved disability outcome in 87% of
      cases after surgery at a median postoperative follow-up of 29 months. All the
      patients showing significant improvement in FLS were preoperatively in scale 4 or
      more, and all the patients whose treatment failed were in scale 3 or less.
      CONCLUSION: We recommend continued use of ESD in indicated patients. We found a
      positive relation between preoperative distress level of the patient and
      postoperative improvement in FLSs; any such relationship should be investigated
      with a larger sample.

PMID- 16788427
TI  - Rehabilitation of patients with conductive hearing loss and moderate mental
      retardation by means of a bone-anchored hearing aid.
AB  - OBJECTIVE: To evaluate whether the bone-anchored hearing aid (BAHA) can be
      applied successfully to patients with conductive hearing loss and moderate mental
      retardation. STUDY DESIGN: Retrospective clinical evaluation. SETTING: Tertiary
      referral center. PATIENTS: Twenty-two patients with congenital moderate mental
      retardation and conductive or mixed hearing loss were selected to receive a BAHA
      at the University Medical Centre Nijmegen, the Netherlands. Four of them were
      fitted despite a limited air-bone gap. INTERVENTION: Rehabilitative BAHA
      application. MAIN OUTCOME MEASURES: Implantation results, skin reactions, and
      audiological data were evaluated during a mean follow-up of 36 months. RESULTS:
      All the patients were still using the BAHA 7 days a week and for more than 8
      hours a day after a follow-up period between 5 and 96 months. Two implants (9%)
      were lost due to insufficient integration but were reimplanted successfully. With
      the BAHA, mean free-field thresholds showed a clear mean improvement of 9 dB
      compared with the previous hearing aid. Considerable improvements in daily
      activities were seen in at least five patients. CONCLUSION: Moderate mental
      retardation should no longer be considered as a contraindication for BAHA
      application. Although implant loss was low, extra attention may be required from
      the personal care providers to maintain the percutaneous implant. The BAHA was
      well-accepted by the patients with moderate mental retardation and was being used
      for most of the day. Implementation of the BAHA as hearing aid treatment in
      patients with moderate mental retardation proved to be sufficiently effective and
      may have strongly positive effects on activities at school or at work.

PMID- 16788428
TI  - Bilateral giant cholesterol granulomas of the temporal bones.

PMID- 16788429
TI  - Intratemporal facial neurofibroma.

PMID- 16788430
TI  - Cholesterol granuloma in the tympanic membrane.

PMID- 16788431
TI  - Sesamoid bone in the stapediovestibular articulation with conductive hearing
      loss.

PMID- 16788432
TI  - [Changes in legislation governing biomedical research].

PMID- 16788433
TI  - [Lung perfusion, physiologic dead space and exercise-induced pulmonary arterial
      hypertension: running for recruitment].

PMID- 16788434
TI  - [Lung cancer--the unhappy consequences of equality].

PMID- 16788435
TI  - [Incidence of lung cancer in Bas-Rhin, France: trends and projection for 2014].
AB  - INTRODUCTION: In France lung cancer is the second most common cancer in men and
      the fourth most common in women. In the department of Bas-Rhin the incidence is
      increasing by 0.1% per annum in men and by 4.4% in women. The aim is to analyse
      and predict the trend of lung cancer incidence in Bas-Rhin from 1975 to 2014.
      METHODS: The incidence data from 1975 to 1999 were extracted from the Bas-Rhin
      cancer registry. Population estimates (2594 years) were made for the period 1975
      2014. Predictions were based on a Bayesian age-period-cohort model. RESULTS:
      Between 1975 and 1999 the incidence of lung cancer increased by 4.5% p.a. in
      women. In men it increased by 1.6% p.a. between 1975 and 1989 and then
      diminished. For the periods 2000-2004, 2005-2009 and 2010-2014 respectively the
      rates should reach 25.6, 32.9 and 42.8 per 100,000 in women and 117.5, 111.6 and
      110.1 per 100,000 in men. CONCLUSIONS: Increasing tobacco smoking among women and
      a reduction among men could be one of the reasons for the respective increasing
      and decreasing incidences.

PMID- 16788436
TI  - [The progression of lung cancer incidence in France (1978-2000)].
AB  - INTRODUCTION: Lung cancer is the most common cause of death from malignant
      disease in the world. Our objective was to describe the progression of this
      cancer's incidence, and the changing distribution of histological types in France
      between 1978 and 2000. METHODS: National incidence rates were obtained by
      modelling lung cancer incidence data provided by the French cancer registries,
      taking into account national mortality data. These registries also provided
      information about histological type. RESULTS: In the year 2000, with 28,000
      estimated new diagnoses, lung cancer represented 10.0% of all incident cancers
      and was responsible for 18.1% of deaths from cancer. From 1980 to 2000, the
      incidence rose from 47.4 to 52.2 per hundred thousand in men and from 3.7 to 8.6
      per hundred thousand in women. The risk of developing lung cancer, which remained
      constant in men, has increased considerably (+451%) between the generation of
      women born in 1953 and those born in 1913. The proportion of epidermoid cancers
      has dropped whilst that of adenocarcinomas has risen sharply. CONCLUSIONS: The
      last few years have seen a large increase in the incidence of lung cancer in
      women and an increasing incidence of adenocarcinoma in both men and women.

PMID- 16788437
TI  - [Is the severity of occupational asthma related to the molecular weight of the
      allergen?].
AB  - INTRODUCTION: The aim of the study was to compare the characteristics of
      occupational asthma (OA) resulting from sensitisation to allergens of high (HMW)
      or low (LMW) molecular weight. METHODS: All new cases of allergic OA seen in an
      occupational health department between January 2001 and March 2004 were included.
      The patients underwent a standardised assessment including a questionnaire, skin
      tests, spirometry and measurement of non-specific bronchial reactivity. They were
      divided into 2 groups depending on the molecular weight of the causal agent
      (groups HMW and LMW). RESULTS: 77 patients were included, 30 in the HMW group and
      47 in the LMW group. No significant difference in severity at the time of
      diagnosis was found between the two groups (symptoms, spirometry, PD20
      methacholine) but the time between the first symptoms and diagnosis was longer in
      the HMW group (7.1 +/- 7.8 years against 3.2 +/- 4.1 years, p = 0.01). Atopy was
      more common in the HMW group (57% vs. 27%, p = 0.01). CONCLUSION: The severity of
      OA at the time of diagnosis does not appear to be influenced by the molecular
      weight of the causal agent.

PMID- 16788438
TI  - [Cardiopulmonary exercise testing in exercise-induced pulmonary hypertension].
AB  - OBJECTIVE: To determine the accuracy of cardiopulmonary exercise-testing (CPET)
      in detecting exercise-induced pulmonary hypertension. BACKGROUND: CPET plays a
      key role in the investigation of exertional breathlessness. Exercise-induced
      pulmonary hypertension has been recently demonstrated to be a cause of exertional
      dyspnea. However, the features of CPET associated with the condition are still
      unknown. METHODS: We prospectively studied CPET and exercise echo-cardiography
      characteristics in 39 patients complaining of exertional breathlessness. Patients
      could be divided into 3 groups as follows: 1) control subjects having normal
      pulmonary arterial pressure at rest [pulmonary arterial systolic pressure < 35
      mmHg] and at peak exercise [pulmonary arterial systolic pressure < 45 mmHg]; 2)
      patients having exercise-induced PH; 3) patients having resting PH. Results from
      CPET have been analyzed within each group. RESULTS: Patients developing exercise
      induced PH revealed an increased VD/VT ratio and CO2 gradient (P[a-ET]CO2) at
      peak exercise compared to controls (VD/VT at 0.38 +/- 0.1 vs 0.29 +/- 0.11 and
      P[a-ET]CO2 at 4,6 +/- 3,1 vs 1 +/- 3,8 mmHg). VD/VT and P[a-ET]CO2 were increased
      in patients with resting PH. A VD/VT ratio at peak exercise higher than 0.34 was
      72.7% sensitive and 71% specific in predicting exercise-induced PH. Positive and
      negative predictive values were 72.7% and 70.1% respectively. CONCLUSION:
      Patients with exercise-induced PH did not decrease or may increase dead space
      during exercise. Therefore CPET may be a useful tool in selecting patients who
      need to undergo further exercise haemodynamic investigations.

PMID- 16788439
TI  - [Gefitinib treatment for carcinomatous meningitis in non-small cell lung cancer].
AB  - BACKGROUND: Carcinomatous meningitis is a major complication in Non Small Cell
      Lung Cancer (NSCLC). Despite treatment with radiotherapy alone or in combination
      with intrathecal and systemic chemotherapy, its prognosis remains poor.
      OBSERVATION: We report a case of a female non-smoker with adenocarcinoma with
      bronchoalveolar features presenting with carcinomatous meningitis three years
      after the diagnosis of her primary tumour. Gefitinib treatment was proposed
      because of the persistence of meningitic symptoms despite cranial irradiation.
      Clinical response was observed within 3 weeks and lasted for 9 months.
      CONCLUSION: Gefitinib may be effective in treating carcinomatous meningitis
      complicating NSCLC and should be considered in this situation given the absence
      of effective alternatives.

PMID- 16788440
TI  - [Management of postoperative chylothorax].
AB  - INTRODUCTION: A chylothorax can occur following any intrathoracic procedure. It
      is generally straightforward to make the diagnosis but optimal management can be
      problematic. METHODS: Between 1995 and 2002, three women and one man aged from 13
      to 58 years were treated for chylothorax after thoracic surgery. Their initial
      illnesses were a right pulmonary hydatid cyst associated with hepatic disease, a
      tumour of the posterior mediastinum, an oesophageal carcinoma and metastases in
      the left lung. RESULTS: These patients had: a pulmonary and hepatic cystectomies,
      a resection of the mediastinal tumor, an Akyama oesophagectomy and a resection of
      four left pulmonary metastases. Chylothorax became apparent post operatively
      between the 1st and the 4th day. All patients were treated with a medium-chain
      triglyceride diet. Two patients were re-explored with ligation of lymphatic
      vessels. One woman who did not have further surgery was treated with etilefrine.
      In the patient who had had an oesophagectomy, chylothorax persisted after re
      operation. He was successfully treated by talc pleurodesis via a chest drain,
      which prevented further recurrence. CONCLUSIONS: In the management of
      postoperative chylothorax, medical treatment must be started early but surgery
      should not be delayed as operative risk is increased by the development of
      malnutrition and immune deficiency.

PMID- 16788441
TI  - [Isoniazid induced neuropathy: consider prevention].
AB  - INTRODUCTION: Antituberculous treatment is effective but has numerous side
      effects. Among these isoniazid induced neuropathy is easily preventable. CASE
      REPORT: A female patient of 42 years, infected with HIV, presented with general
      deterioration associated with an interstitial pulmonary infiltrate and
      mediastinal lymphadenopathy. Tuberculosis was not confirmed bacteriologically but
      she responded to antituberculous treatment. Three months later she developed
      distal leg pains extending proximally. There was superficial sensory impairment
      up to the groins and loss of the ankle reflexes. The dose of isoniazid was
      reduced from 5 to 2.5 mg/kg/day on account of slow acetylator status and
      treatment with pyridoxine 250 mg/day commenced. The clinical signs resolved in a
      few weeks. CONCLUSIONS: Isoniazid neuropathy develops in the presence of risk
      factors (HIV, alcoholism, diabetes, renal failure, malnutrition, pregnancy and
      lactation, neurotoxic medication) and manifests itself initially by burning feet.
      Pyridoxine is preventative in low dosage and curative in high dosage. The
      development of symptoms should lead to measurement of acetylator status, and a
      reduction of the isoniazid dose to 3 mg/kg/day or even less in slow acetylators.

PMID- 16788442
TI  - [Unusual thoracic complications of old tuberculosis].

PMID- 16788444
TI  - [Scholarships in respiratory medicine, 2005].

PMID- 16788443
TI  - [Cohort KBP-2000-CPHG: Evaluation of factors influencing survival in lung
      cancer].
AB  - INTRODUCTION: Lung cancer continues to have a poor prognosis despite some
      therapeutic advances. BACKGROUND: The last fifteen years has seen a dramatic
      increase in the incidence of lung cancer in women and an increased proportion of
      adenocarcinomas in both sexes. A study of overall survival as a function of
      gender and other prognostic factors has been established using the cohort of
      patients from the study KBP-2000-CPHG. METHODS: KBP-2000-CPHG is an
      epidemiological study carried out throughout the year 2000 looking at
      histologically confirmed primary lung cancers managed in general hospitals. 5,667
      patients have been included. The study of survival looks at 2 and 5-year
      outcomes. The date and cause of death are recorded for each patient. In the
      absence of these data the date of the last contact is noted. If this is less than
      4 months the patient is considered to be alive. If more than four months have
      elapsed a graduated strategy for establishing vital status is pursued which
      involves reviewing records from various different sources. RESULTS AWAITED: A
      preliminary review of the data was undertaken between September 2004 and March
      2005 which obtained data on 5 567 patients. The analysis of survival according to
      sex and other forecast prognostic factors is underway.

PMID- 16788502
TI  - [Subacute infiltrative lung disease with ground glass patterns on x-ray:
      observation].

PMID- 16788504
TI  - [Infiltrative lung disease with alveolar density on x-ray: observation].

PMID- 16788506
TI  - [Alveolar hemorrhages: observation].

PMID- 16788508
TI  - [Chronic infiltrative lung disease with honeycomb pattern: observation].

PMID- 16788510
TI  - [Sarcoidosis and granulomatous disease: observation].

PMID- 16788512
TI  - [Sarcoidosis and granulomatous disease: observation].

PMID- 16788514
TI  - [Sarcoidosis and granulomatous disease: observation].

PMID- 16788516
TI  - [Role of surgical lung biopsy in exploring interstitial lung disease (excluding
      immunodepressive conditions)].

PMID- 16788517
TI  - [Treatment of idiopathic pulmonary fibrosis].

PMID- 16788518
TI  - [How should advanced forms of diffuse infiltrating lung disease be treated: role
      of new treatments and transplantation indications].

PMID- 16788519
TI  - [Chemotherapy at home for thoracic malignancies].

PMID- 16788520
TI  - [Adolescent smoking. What are the issues?].

PMID- 16788521
TI  - [Physiological factors influencing pulmonary capillary volume and membrane
      diffusion].
AB  - BACKGROUND: The lung is subject to many physiological changes during life. The
      aim of this study was to identify factors that influence gas transfer, which
      depends on membrane diffusion (Dm) and pulmonary capillary blood volume (Vc).
      METHODS: Dm and Vc measurements were performed at rest in 135 healthy patients
      divided into three groups according to age and after an exercise in 22 non
      trained children. Measurements were made using a simultaneous transfer of 2
      gases; nitric oxide (NO) and carbon monoxide (CO). RESULTS: Dm was correlated
      with height in the adult group and with weight in the elderly group. Vc was not
      correlated with weight in the three studied groups, but correlated with height in
      the adult group. Dm and Vc declined with age (p<0.05), For Dm this started at the
      age of forty whereas a fall in Vc was apparent at sixty. Pulmonary and vascular
      ageing could explain these results. Sex had no effect on Dm and Vc. Exercise led
      to a significant rise in Dm and Vc (p<0.05) which was attributed to pulmonary
      capillary distension and recruitment. CONCLUSION: Knowledge of these
      physiological changes permits a better understanding of pathological changes.

PMID- 16788522
TI  - [Knowledge of the risks of smoking in patients admitted to a respiratory clinic
      in Senegal].
AB  - INTRODUCTION: Tobacco smoking is truly a modern plague. The WHO estimates that
      there are 1.3 billion smokers worldwide, about a third of the world's population.
      In various studies in Senegal the prevalence of smoking has varied between 16 and
      36%. The risks associated with smoking are well established. However it is also
      well established that 'knowledge of risks alone is not sufficient to modify
      behaviour.' We undertook a study to assess knowledge of the risks of smoking
      among patients admitted to The Pulmonology Clinic of the Centre Hospitalier
      National de Fann de Dakar. PATIENTS AND METHODS: All patients admitted to the
      clinic between 1st December 2003 and 31st May 2004 were enrolled into this
      prospective, cross-sectional study. A questionnaire in French was administered
      together with the Fagerstrom test of clinical addiction. RESULTS: Of 343 patients
      admitted 75 (22%) were smokers. Only 2 (2.6%) of the smokers were female. As in
      previous studies, smoking was associated with social disadvantage. 34.7% of
      smokers had attended school to primary level only and 33.3% had had no schooling
      at all. Mean age of starting smoking was 16 (range 9 to 38 years). The monthly
      cost of smoking to individuals was estimated at between 2 and 45% of the
      Guaranteed Minimum Wage (SMIG). 44% of smokers also consumed alcohol and 2.6%
      smoked cannabis. More than two thirds of patients (68%) thought that smoking
      caused ill health. The majority of subjects (93.3%) had stopped smoking, at least
      since admission, though 6.7% continued to smoke. Previous consumption was
      estimated as a mean of 20 pack-years. Nicotine dependence was defined as medium
      in 37 patients (49.3%). CONCLUSION: Certain diseases such as malaria,
      tuberculosis and AIDS exist at endemic levels producing considerable morbidity
      and mortality. We should not allow the epidemic of smoking to continue.
      Collective action, particularly by pneumologists is required.

PMID- 16788523
TI  - [Validation of the French version of the Princess Margaret Hospital Patient
      Satisfaction with their Doctor Questionnaire].
AB  - BACKGROUND: The evaluation of patient satisfaction receives increasing attention
      partly due to pressure from state agencies involved in the administration of
      health care. Outpatients' satisfaction with their doctor is a major component of
      total patient satisfaction. However, a validated instrument for assessing this
      has not previously been available in French. PATIENTS AND METHODS: The Princess
      Margaret Hospital Patient Satisfaction with Doctor Questionnaire (PMH/PSQ-MD) is
      a recently validated tool available in English for this purpose. A three-step
      procedure was conducted to obtain a validated French translation of the PMH/PSQ
      MD. Subsequently, outpatients receiving chemotherapy, symptomatic treatment or
      attending a follow-up clinic were approached to participate in the study and
      complete the questionnaire. Acceptability and reliability (Cronbach's alpha
      score), as well as internal and external (Pearson correlation coefficient with
      the Patient Satisfaction Questionnaire IV) validities were studied. RESULTS: 137
      patients were approached and 116 fully completed the study. The PMH/PSQ-MD's
      acceptability was high (<10% of non-responders). Internal validity was also high
      (Cronbach's alpha score > 0.7 for each dimension). External validity in
      comparison with the PSQ IV was high as well. Women demonstrated higher
      satisfaction scores, while age had no influence on patient satisfaction.
      CONCLUSIONS: The F-PMH/PSQ-MD is a questionnaire which addresses outpatients'
      satisfaction with their doctor, and is now available for research purpose as well
      as for daily practice.

PMID- 16788524
TI  - [Smoking and the adolescent. An inquiry into motivation and knowledge of the
      effects of tobacco].
AB  - INTRODUCTION: The nicotinism at the teenagers is a concern of public health. The
      objective of our prospective and descriptive investigation was to better
      include/understand the nicotinic practices of the teenagers. METHODS: A
      questionnaire was distributed to the children from 12 to 16 years presenting at
      the Paediatric emergency department of Le Havre from September 2003 on May 2004.
      The items collected related to the practices and knowledge on the nicotinism.
      RESULTS: Hundred answers were collected at teenagers with an average age 14
      years. We found 35% of smokers. Among smokers, the average age of the beginning
      of the nicotinism is at 12,2 years. The girls smoke significantly more than the
      boys (42% versus 22%, p<0.01). Sex ratio is 2,8 (26 girls and 9 boys). The degree
      of dependence was evaluated by the score of Fagerstrom. Half of the questioned
      teenagers are fairly with strongly dependent (score > 5), in spite of a daily
      consumption of 5 cigarettes on average. The consumption of other "drugs" was
      announced at 51.5% of the smokers. On the 100 teenagers, 7 stopped smoking, but 3
      think of smoking a day again. The teenagers of single-parent family or separate
      smoke significantly more than if the parents are in couple (58.3% versus 41.6,
      p<0.01). The class of third represented the peak of making of contact with the
      tobacco. CONCLUSION: The tobacco at the teenagers is a control at the risk
      justifying the continuation of the actions of prevention by the whole of the
      doctors.

PMID- 16788525
TI  - [Lung cancer in women: surgical aspects related to gender].
AB  - INTRODUCTION: Lung cancer is becoming more and more common in women where it
      presents significant differences at both clinical and therapeutic levels. Our
      purpose was to study those associated with surgical treatment. PATIENTS AND
      METHODS: 2972 patients were operated on between 1984 and 2002: 2480 men and 492
      women. These two populations were compared (age, past history, investigations,
      interventions, TNM stage, long term survival and causes of death). RESULTS: The
      number of women increased with time; they were younger than the men, smoked less,
      had the same past history of cancer but less past medical history, and
      comorbidity. They underwent less pneumonectomies and had a lower postoperative
      mortality. Tumour size was smaller (39.5 vs 43.5cm, p=0.0001); N0 and stage I
      tumours were more frequent (52.6% vs 46% p=0.0074). Long term survival was better
      (48.6% vs 43.1%, p=0.016), particularly in stage I and with a past history of
      cancer. It was identical in stage III despite a higher incidence of multisite N2
      disease. Smoking and adenocarcinoma were more frequent before the menopause and
      N2 prognosis deteriorated with age. CONCLUSION: These results confirm
      characteristics peculiar to lung cancer in women and warrant further
      investigation aimed at their better understanding. However, in multivariate
      analysis gender does not appear to be an independent prognostic factor.

PMID- 16788526
TI  - [Economic analysis of home based versus hospital outpatient chemotherapy in stage
      IV non small cell lung cancer].
AB  - BACKGROUND: French law and government decisions have induced new development for
      home base treatments. The objective was to compare cost of home base chemotherapy
      (HBC) versus outpatient infusions, for non small cell lung cancer (NSCLC).
      METHODS: 10 patients were selected in each category. D8 of their cycles was
      performed at home compared to outpatient infusion. Costs were based on national
      fees with cytostatic drugs as supplement. The real cost was also assessed through
      a specific questionnaire. RESULTS: 30 D8 infusions were carried out at hospital
      and 24 D8 infusions at home. Average cost by cycle was 2,829.51 euros [2 560.74-3
      147.02] for hospital infusion, 2,372.50 euros [1 962.75-2 792.88] for HBC (
      16.15%). Difference was -457.01 euros by cycle [-919.74; 26.82]. Real costs by
      injection for BHC was 484.42 euros [424.18; 540.32] versus a fee of 699.89 euros
      [643.64; 750.23]. There were no difference in terms of adverse events.
      CONCLUSION: HBC for NSCLC is feasible. Average costs by cycle is lower of 16%
      versus hospital infusion. The results of this non randomized study had to be
      confirm by further clinical trials.

PMID- 16788527
TI  - [Splenic metastasis from a bronchial carcinoma].
AB  - INTRODUCTION: Isolated splenic metastases from a bronchial carcinoma, without
      other visceral metastatic involvement, are exceptionally uncommon. CASE REPORT:
      The authors report the finding of an isolated splenic metastasis 21 months after
      a left pneumonectomy for an undifferentiated large cell carcinoma, initially
      staged pT3N1M0. The splenic metastasis presented as a major deterioration in
      general health and sharp pains in the left hypochondrium. Splenectomy confirmed
      the metastatic nature of the splenic tumour and relieved the severe abdominal
      pains. Two years after the splenectomy and with out adjuvant treatment the
      patient remains in complete remission. CONCLUSION: Splenectomy for a metastasis
      from a bronchial carcinoma should avoid the later complications of this type of
      metastasis: severe abdominal pain, splenic rupture and compression of
      neighbouring vessels. If the bronchial carcinoma is controlled locally and the
      splenic metastasis is isolated, splenectomy offers, perhaps, a further chance of
      prolonged survival.

PMID- 16788528
TI  - [Hypersensitivity to carboplatin. An effect of generic drugs?].
AB  - INTRODUCTION: Carboplatin is a chemotherapeutic agent used frequently in thoracic
      medicine on account of its relatively good tolerance. Nevertheless
      hypersensitivity reactions have been described. CASE REPORTS: We report the cases
      of 2 patients, treated for undifferentiated bronchial carcinoma and carcinoma of
      the breast, presenting with hypersensitivity reactions to carboplatin developing
      after 6 and 8 courses respectively. The first patient presented with an irritant
      maculo-papular rash and the second with severe hypotension and bronchospasm.
      Neither of these reactions was fatal. Both of these reactions occurred when
      generic carboplatin was substituted for the propriety preparation. CONCLUSION:
      Hypersensitivity reactions to carboplatin should be recognised by respiratory
      physicians on account of their potential seriousness and their occurrence after
      several courses of treatment. This takes on particular importance at a time when
      plans for domiciliary treatment of patients are being considered. In addition a
      national survey of hypersensitivity to carboplatin should be considered by the
      regional drug safety centres.

PMID- 16788529
TI  - [Intestinal metastases from lung cancer].
AB  - INTRODUCTION: Intestinal metastasis from primary lung cancers is rare and usually
      asymptomatic. CASE REPORT: We report two cases of symptomatic small bowel
      metastasis. The first one presented with a persistent anaemia occurring in a 54
      year old man who had undergone a left lower lobectomy for a large cell carcinoma.
      The second case was a 75 year old man who presented with peritonitis which led to
      discovery of a lung primary. CONCLUSION: Intestinal metastasis can be the
      presenting feature of, or complicate lung cancer. Symptomatology depends on
      metastasis localisation. Their treatment is difficult and they are associated
      with a poor prognosis.

PMID- 16788530
TI  - [Gastropleural fistula presenting with a pyopneumothorax in pregnancy].
AB  - INTRODUCTION: Gastropleural fistula has only rarely been described in the
      literature, typically presenting with evidence of left-sided pleural infection.
      CASE REPORT: The diagnosis may be suggested by the occurrence of chest pain and
      repeated vomiting with the diagnosis confirmed by microbiological examination of
      the pleural fluid and appropriate radiological investigations. The fistula occurs
      most frequently after abdominal or anterior thoracic surgery. Generally, surgical
      repair should be performed urgently but in the case that we describe occurring
      during pregnancy, surgery was delayed for 10 weeks until a caesarean section
      could be performed. CONCLUSION: In the presence of left-sided basal pleuritic
      chest pain in the context of a possible gap in the diaphragm the diagnosis of
      gastropleural fistula should be considered. Treatment is usually a medico
      surgical emergency.

PMID- 16788531
TI  - [Multifocal tuberculosis (palpebral and pleural) in an immunocompetent woman].
AB  - INTRODUCTION: Tuberculosis of the eyelid and its development in the setting of
      multifocal tuberculosis is exceptionally rare. CASE REPORT: The authors report a
      new observation of multifocal tuberculosis in a non-immunosuppressed woman of 28
      years with histologically confirmed pleural and palpebral involvement. A
      paradoxical reaction was seen following the initiation of anti-tuberculous
      treatment with appearance of new manifestations (thoracic cold abscesses).
      CONCLUSION: The authors draw attention to this rare localisation and to the
      paradoxical reactions during treatment, emphasising the need for early diagnosis
      to avoid local and remote complications.

PMID- 16788532
TI  - [Unusual site of primary synovial sarcoma: the lung].

PMID- 16788533
TI  - [Publishing in the Journal de Radiologie: an absolute necessity!].

PMID- 16788534
TI  - [Orbital blow-out fractures].
AB  - Blow-out fractures, lateral fractures of the face, involve only the inferior and
      sometimes the medial wall of the orbit. Clinical diagnosis is not always obvious,
      and CT is helpful to confirm diagnosis and also detect some failures of surgical
      treatment: improper position or size of the graft. MRI is valuable to evaluate
      post-surgical infections.

PMID- 16788535
TI  - [Functional magnetic resonance imaging in clinical practice].
AB  - In the last decade, functional MRI (fMRI) has become one of the most widely used
      functional imaging technique in neurosciences. However, its clinical applications
      remain limited. Despite methodological and practical issues, fMRI data has been
      validated by different techniques (magnetoencephalography, Wada test, electrical
      and magnetic stimulations, and surgical resections). In neurosurgical practice,
      fMRI can identify eloquent areas involved in motor and language functions, and
      may evaluate characteristics of postoperative neurological deficit including its
      occurrence, clinical presentation and duration. This may help to inform patients
      and to prepare postoperative care. fMRI may also identify epileptic foci. In
      neurological practice, fMRI may help to determine prognosis of recovery after
      stroke, appropriate medication, and rehabilitation. fMRI may help to identify
      patients at risk of developing Alzheimer disease. Finally, cerebrovascular
      reactivity imaging is an interesting approach that might provide new radiological
      insights of vascular function.

PMID- 16788536
TI  - [Role of modern cross-sectional imaging in thanatology: a pictorial essay].
AB  - The development of new imaging modalities such as computed tomography and
      magnetic resonance imaging is a new phenomenon in thanatology. The growing
      accessibility to these technologies allows, under some conditions, the
      acquisition of cross-sectional images on cadavers. The authors present a
      practical pictorial review of post-mortem changes and deadly injuries,
      illustrating the contributions of modern cross-sectional imaging techniques in
      thanatology.

PMID- 16788537
TI  - [Ultrasound features of entesopathy in patients with psoriatic dactylitis].
AB  - PURPOSE: To describe the sonographic features of entesopathy in patients with
      psoriatic dactylitis. Materials and methods. Clinical, radiographic and
      sonographic evaluation of 120 hand joints with clinical abnormality including 20
      fingers in 17 patients with rheumatoid arthritis (RA) and 20 fingers in 17
      patients with psoriatic arthritis (PA). RESULTS: Forty cases of dactylitis. In
      patients with RA: 29 cases of synovitis, 15 cases of tenosynovitis, and 2 cases
      of tendinitis; in patients with PA: 21 cases of synovitis and 3 cases of
      tenosynovitis. Bone erosions were present in RA patients whereas erosions with
      bone production were present in PA patients. A total of 60% of RA and PA patients
      showed erosions on conventional radiographs. Features suggesting entesopathy were
      present in PA patients only: specific changes of P3, capsular hyperostosis and
      periarticular periostitis. CONCLUSION: Based on evaluation of PA patients, it
      seems that sonographic features suggesting entesopathy in patients with
      dactylitis may be present.

PMID- 16788538
TI  - [Arterial duplex and aortic valve stenosis: sensitivity and specificity of
      findings].
AB  - Purposes. In this prospective study, we sought to determine the sensitivity and
      the specificity of arterial Doppler findings of valvular aortic stenosis (VAS).
      PATIENTS AND METHODS: 20 control subjects and 20 patients with various degrees of
      VAS underwent Doppler ultrasound of the carotids, abdominal aorta, renal arteries
      and limb arteries. We analyzed and compared the shape of the spectral profiles,
      peak systolic velocity (PSV), systolic upstroke time (SUT) and systolic upstroke
      index (SUI) of every tracing. The protodiastolic notch (PDN) of the common
      femoral arteries were recorded too. RESULTS: VAS hardly modifies the overall
      shape of the Doppler spectrums of the aorta or limb arteries but it implies a
      biphasic deformation or a doubling of the systolic peak of the neck vessels. We
      also encountered biphasic profiles in renal arteries of patients with tight VAS.
      The PSV, SUI and depth of the PDN tend to diminish in cases of VAS but the
      variations are inconstant and rarely proportional to the severity of the
      narrowing. The increase of the SUT, on the contrary, is linearly correlated to
      the severity of the stenosis in every arterial system: SUTs in the common carotid
      artery, internal carotid artery or brachial artery that are shorter than or equal
      to 70 milliseconds (msec) are the obvious marks of the absence of VAS. It was not
      possible to differentiate between the intermediate stenoses (aortic valve area
      between 0.8 and 2 square centimeters) whereas critical aortic stenoses, whose
      area is less than or equal to 0.7 square centimeter, can be detected by the
      presence of at least two of the four following criteria of SUT: equal to or above
      180 msec for the common carotid, 200 msec for the internal carotid, 130 msec for
      the aorta and 110 msec for the common femoral artery. CONCLUSION: During routine
      arterial Doppler ultrasound, a precise analysis of the spectrums and some SUT
      measurements allow the assessment of the aortic valve.

PMID- 16788539
TI  - [Pericochlear hypodensity on CT: normal variant in childhood].
AB  - PURPOSE: Evaluation of the prevalence of a pericochlear hypodensity on CT in
      children. Materials and methods. This study correlates the findings on temporal
      bone CT to the indications for CT (headache, trauma). Helical CT acquisitions
      using 0,5 mm, 0,6 mm or 0,75 mm slice thickness according to the material
      available, with multiplanar reconstructions. Only patients with significant
      pericochlear hypodensity, larger or equal to 0,4 mm, were taken into account, and
      the curvilinear or nodular nature of the lesion on axial and coronal sections was
      recorded. RESULTS: A pericochlear hypodensity was identified in nearly 40% of
      cases. There was no population predominence according to the indication for the
      CT. The curvilinear type was more frequent on coronal images, with unilateral and
      bilateral involvement being equally frequent. There was no significant difference
      according to the sex. Patients of all ages showed lesions, from newborns to
      adolescents, with increased frequency in childhood. CONCLUSION: This study
      confirms a high prevalence of pericochlear hypodensity in a paediatric
      population, without clinical correlation, which requires prudence when
      interpreting the significance of this CT sign commonly described in association
      with pericochlear otosclerosis and the pericochlear form of osteogenesis
      imperfecta.

PMID- 16788540
TI  - [Pulmonary artery sarcoma during postpartum: CT findings].
AB  - We report the case of a 28 year-old female, who gave birth seven weeks
      previously, presenting with a pulmonary artery leiomyosarcoma discovered on a
      thoracic CT performed for clinical suspicion of pulmonary embolism. This case
      presents two major points of interest: on the first hand, it is a particular
      context (young post-partum patient), with classic symptoms of routine pulmonary
      embolism. On the other hand, the exam clearly demonstrates tumor enhancement,
      which is characteristic but rarely described.

PMID- 16788541
TI  - [Cardiac anatomy and the radiologist].
AB  - We report a case of myocardial infarction due to occlusion of the left anterior
      descending artery seen on a routine chest CT performed in order to exclude aortic
      dissection. This underscores the need for the radiologist to look at the heart
      and coronary arteries on each thoracic CT-scan, even if acquired without EKG
      gating.

PMID- 16788542
TI  - [Asymptomatic pneumothorax diagnosis on pre-biopsy sonogram of the liver].
AB  - Liver biopsy is an invasive procedure which is widely used for the management of
      liver diseases. An asymptomatic pneumothorax was detected on sonography prior to
      biopsy for chronic hepatitis C. The complications from biopsy, potentially
      severe, are decreased by ultrasound guidance. Currently, ultrasound guidance is
      recommended at the time of liver biopsy.

PMID- 16788543
TI  - [Ganglion cyst rupture in the retro-femoral fat: a report of two cases].
AB  - Ganglion cysts are ubiquitous cystic lesions without synovial wall and inconstant
      communication with the articular cavity. The later must nonetheless always be
      carefully looked for. We report two cases of ganglion cyst rupture in the
      retrofemoral fat simulating phlebitis with thigh cellulitis. To the best of our
      knowledge, this has not been previously reported in the literature. Familiarity
      with this entity ensures adequate medical diagnosis and management, avoiding
      unnecessary imaging and laboratory work-up and inappropriate use of anticoagulant
      and antibiotic.

PMID- 16788544
TI  - [What is your diagnosis? Solitary necrotic nodule of the liver].

PMID- 16788545
TI  - [In reference to the article "Circumscribed myositis ossificans"].

PMID- 16788546
TI  - [Partial-facial allograft or allotransplantation of a portion of the face?].

PMID- 16788547
TI  - [Surgical repair of inguinal hernia in the adult Clinical, functional, and
      economic outcomes of surgical practices].
AB  - Inguinal hernia repair is the most commonly performed surgical procedure. Nearly
      one out of three men between 20 and 60 years of age will undergo hernia repair.
      Multiple surgical techniques are available which have comparable clinical
      outcomes but which differ in their functional results and economic impact.
      Despite an extensive surgical literature, no consensus exists regarding an
      optimal technique. This review aims to compare the indications for the three most
      common techniques: 1) the Shouldice repair, 2) the Lichtenstein repair, and 3)
      the laparoscopic hernia repair. To begin with, we present the operative
      principals of each repair along with criteria for evaluation of outcomes.
      Evidence-based outcomes data are then presented. We then address the choice of a
      surgical technique for everyday practice based on these factors. Finally, we
      propose avenues for future clinical research which may improve clinical,
      functional, and economic results in the repair of inguinal hernia of the adult.

PMID- 16788548
TI  - [Surgical management of post-operative peritonitis].
AB  - Post-operative peritonitis usually results from intra-operative or delayed injury
      to a digestive organ; it is accompanied by a high mortality rate. Prognosis is
      directly related to early diagnosis and appropriate re-intervention. Clinical and
      laboratory signs of gravity impose prompt re-operation. Imaging exams such as CT
      will aid in diagnosis and guide the therapeutic approach. Treatment specifically
      adapted to the etiologic cause must be thorough and complete from the start.

PMID- 16788549
TI  - [History of parathyroid surgery].

PMID- 16788550
TI  - [A difficult cholecystectomy].

PMID- 16788551
TI  - [Treatment of fistula-in-ano].

PMID- 16788552
TI  - [Fogarty catheter embolectomy for acute arterial occlusion with healthy distal
      run-off].

PMID- 16788553
TI  - [Resection of parathyroid adenoma under local anesthesia].

PMID- 16788555
TI  - [1st Francophonic Congress of Digestive and Hepatobiliary Surgery Paris, 8-10
      Decembre 2005].

PMID- 16788554
TI  - [Pseudo-papillary tumor of the distal pancreas].

PMID- 16788556
TI  - [Role of biliary MRI in the diagnosis and management of bile peritonitis due to
      closed trauma of the liver].

PMID- 16788557
TI  - [Small intestinal metastasis from non-intestinal tumors 1. Which primary
      tumors?].

PMID- 16788558
TI  - [2. Presenting as intestinal obstruction].

PMID- 16788559
TI  - Masculinization of female gastropod mollusks induced by organotin compounds,
      focusing on mechanism of actions of tributyltin and triphenyltin for development
      of imposex.
AB  - Imposex, the superimposition of male-type genital organs (penis and vas deferens)
      on female gastropods, is cause-specific and induced by low concentrations of
      certain organotins, such as tributyltin (TBT) and triphenyltin (TPT) from
      antifouling paints. Reproductive failure may be observed at severely affected
      stages. The history of imposex study and the legislation of organotins are
      summarized. The present statuses of gastropod imposex and organotin pollution in
      Japan, together with endocrine disruption observed in abalones, are also
      summarized, on the basis of the results of the field studies of the rock shell
      (Thais clavigera) conducted at 174 locations along the Japan coast between
      January 1999 and November 2001, the histopathological and analytical chemical
      studies of the ivory shell (Babylonia japonica), and both field and laboratory
      studies of the abalone (Haliotis madaka and H. gigantea). The fundamental
      knowledge of the endocrinology of gastropod mollusks is briefly described. Four
      hypotheses, such as that of aromatase-inhibition, regarding the induction
      mechanism of imposex induced by organotins in gastropods are reviewed. Finally, a
      new hypothesis that states that retinoid X receptor (RXR) plays an important role
      in inducing the development of imposex, i.e., the differentiation and growth of
      male-type genital organs in female gastropods, is reviewed and discussed to
      clarify the entire mode of action of TBT or TPT in the development of imposex in
      gastropods.

PMID- 16788561
TI  - Endocrine disruptive effects of inorganic arsenicals.
AB  - Although inorganic arsenicals are toxic and carcinogenic in humans, inorganic
      arsenite has recently emerged as a highly effective chemotherapeutic agent for
      acute promyelocytic leukemia (APL). Recently, the number of arsenic-related
      publications has greatly increased, but the effects of arsenicals on the
      endocrine system have not been well studied. A number of in vivo studies about
      only inorganic-arsenical-induced endocrine-disruptor-like effects have been
      conducted using mouse models, and they demonstrated that inorganic arsenicals
      might act as an estrogen-like chemical in vivo and induce some tumors in mice. In
      most mammalian species, however, inorganic arsenicals are enzymatically
      methylated as a detoxifying metabolic response. Thus, studies of endocrine
      disruptive effects of methylated arsenicals are also needed for a clinical
      understanding of this attractive metalloid in the near future.

PMID- 16788560
TI  - Molecular targets of organotin compounds in endocrine disruption: do organotin
      compounds function as aromatase inhibitors in mammals?
AB  - Tributyltin (TBT) and triphenyltin (TPT) cause masculinization in female
      mollusks. These compounds may act as potential competitive inhibitors of
      aromatase, which converts androgens to estrogens, although effective
      concentrations are high. TBT and TPT may, therefore, increase the levels of
      unconverted androgens in invertebrates and vertebrates. However, at
      concentrations effective for aromatase inhibition, they are generally toxic to
      mammalian cells. These compounds markedly enhance aromatase activity and human
      chorionic gonadotropin (hCG) production, along with their mRNA expression, at
      very low concentrations in human choriocarcinoma cells. In ovarian granulosa
      cells, these compounds suppress aromatase gene expression at the same low
      concentrations. Therefore, it is suspected that, in mammals, these organotin
      compounds affect target molecules that regulate the gene expressions of aromatase
      and hCG, rather than functioning as aromatase inhibitors. Recently, it has been
      demonstrated that TBT and TPT directly bind to the retinoid X receptor (RXR) and
      the peroxisome proliferator-activated receptor (PPAR) gamma with high affinity
      and function as transcriptional activators. These compounds promoted adipocyte
      differentiation, which is triggered by the PPAR gamma/RXR signaling pathway. They
      may, therefore, exert their toxic effects through the activation of these
      pathways in mammals. Here, we review the potential endocrine disruption of
      organotin compounds via these nuclear receptors in mammals.

PMID- 16788562
TI  - New aspects of cadmium as endocrine disruptor.
AB  - Cadmium (Cd) is an industrial and environmental pollutant that exerts adverse
      effects on a number of organs in humans and animals. Reproductive organs, such as
      the testis and placenta, are sensitive to the toxic effects of Cd. In animal
      experiments, high-dose exposure to Cd induced severe testicular interstitial
      hemorrhage with edema, and increased incidence of fetal death and placental
      necrosis. Low-dose exposure to Cd affects steroid synthesis in male and female
      reproductive organs. In 1998, the Ministry of Environment in Japan listed Cd in
      the strategy plan SPEED98 as one of the chemicals suspected of having possible
      endocrine disrupting activity. Recently, it has been shown that Cd has potent
      estrogen- and androgen-like activities in vivo and in vitro, by directly binding
      to estrogen and androgen receptors. However, the precise mechanisms underlying
      the effects of Cd as an endocrine disruptor remain to be elucidated. In this
      review, we will discuss evidence thus far presented concerning the effects of Cd
      on the endocrine system.

PMID- 16788563
TI  - Mice strain differences in effects of fetal exposure to diesel exhaust gas on
      male gonadal differentiation.
AB  - We have shown that in ICR pregnant mice exposed to diesel exhaust (DE), mRNA
      expression of mallerian inhibiting substance (MIS) and a steroid hormone
      transcription factor (Ad4BP/SF-1), which are essential in male gonadal
      differentiation, decreases in a DE concentration-dependent manner. To further
      investigate whether these effects differ among strains, we conducted the present
      study in 3 different strains: ICR mice, ddY mice, and C57BL/6J mice. The response
      to DE exposure differed among the 3 strains. In C57BL/6J male fetuses, only MIS
      mRNA expression significantly decreased, and in ddY male fetuses, there was no
      change in either MIS or Ad4BP/SF-1 mRNA expression. Although there was no
      definite correlation between mouse strain characteristics and differences in the
      effects of DE, our findings suggest strain-related variations in DE sensitivity
      with respect to gene expression regulating male gonadal differentiation.

PMID- 16788564
TI  - Production of low-estrogen goldfish diet for in vivo endocrine disrupter test.
AB  - A low-estrogenic diet for goldfish Carassius auatus was produced for an in vivo
      estrogen activity test, because commercial fish feed has estrogenic activity and
      may affect the results of estrogen assays. The newly produced diet (FD5) was
      formulated with defatted rice bran and casein, and did not contain any soybean
      meal or fish meal. Phytoestrogen contents (genistein, daidzein, equol, and
      coumestrol) of FD5 were measured by liquid chromatography-mass spectroscopy/mass
      spectroscopy (LC-MS/MS) and compared with those of the commercial trout diet (TD)
      and carp diet (CD). The genistein, daidzein, and coumestrol contents of TD and CD
      were much higher (5-2000 times) than those of FD5, but equol was detected only in
      FD5. Estrogenic activity of the fish diets was estimated in vitro by the yeast
      estrogen-screen assay (YES assay). The estrogenic activity was detected in TD and
      CD, but not in FD5. The in vivo estrogenic activity of the diets was examined by
      determining the production of vitellogenin in male goldfish. When male goldfish
      were fed TD or CD, plasma vitellogenin levels increased, but fish that were fed
      FD5 maintained low vitellogenin levels. These results indicate that FD5 produced
      in the present study has a low estrogenic activity, and FD5 would be suitable for
      the in vivo estrogen activity test using goldfish.

PMID- 16788565
TI  - Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in
      normal and cancerous kidney cortex.
AB  - There is increasing evidence that polymorphisms of the adenosine 5' triphosphate
      membrane transporters ABCB1 (P-glycoprotein, MDR1) may affect expression and
      function, whereas less information is available about the impact of ABCC2
      (multidrug resistance-associated protein (MRP2)) single-nucleotide polymorphisms
      . Particularly, their role in human kidney for drug elimination and in the
      etiology of renal cell carcinoma is poorly understood. ABCB1 and ABCC2 mRNA and
      protein expression levels were determined by real-time polymerase chain reaction
      or immunohistochemistry in kidney cancer and adjacent unaffected cortex tissue of
      82 nephrectomized renal cell cancer (RCC) patients (63 clear-cell RCC (CCRCC), 19
      non-CCRCC). The DNA of all patients was genotyped for ABCB1 -2352G>A, -692T>C,
      2677G>T/A (Ala893Ser/Thr), and 3435C>T, and ABCC2 -24C>T, 1249G>A (Val417Ile) and
      3972C>T. ABCB1 and ABCC2 were less expressed in CCRCC than in normal cortex on
      mRNA as well as on protein level. Although the overall genotype frequency
      distribution did not differ between the patients and a matched control group,
      ABCB1 2677T/A and 3435T genotypes were associated with higher (P=0.02 and P=0.04)
      and ABCC2 -24 T with lower mRNA levels in normal tissues (0.03). The expression
      of ABCB1 and ABCC2 was not related to genetic variants in RCC tissue. In a
      reporter gene assay in HepG2 cells, the ABCC2 -24T construct showed an 18.7%
      reduced activity (P=0.003). In conclusion, ABCB1 and ABCC2 genotypes modulate the
      expression in the unaffected renal cortex of RCC patients, possibly contributing
      to inter-individual differences in drug and xenobiotics elimination. Their role
      in RCC cancer susceptibility or chemotherapy resistance needs further
      elucidation.

PMID- 16788566
TI  - Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase
      gene (FAS) on body mass index and lipid profile in Caucasian children.
AB  - OBJECTIVE: A Val1483Ile polymorphism in the human fatty acid sythase gene (FAS)
      has recently been shown to be associated with lower percentage of body fat and
      substrate oxidation rates in Pima Indians, but its role in other populations has
      not been described. Here, we investigate the effect of this variant on obesity in
      Caucasian children and adolescents. SUBJECTS AND METHODS: In total, 738 Caucasian
      children and adolescents aged 6-17 years of the Leipzig Schoolchildren cohort,
      which constitutes an unselected representative German population and 205 obese
      children (body mass index (BMI) 2.71+/-0.04 SDS) were genotyped for genotype
      phenotype associations. RESULTS: The frequency of the Ile-allele was lower in
      German Caucasians compared with Pima Indians (0.03 compared to 0.10). Using
      generalized linear regression models, there was no effect of the polymorphism on
      BMI in the whole normal population. However, we identified a significant
      interaction effect between sex and genotype (P=0.004). Subsequent sex stratified
      analyses revealed a lower BMI SDS in boys with Ile/Val genotype compared to
      Val/Val (-0.36+/-0.29 vs 0.09+/-0.05, P<0.05), while an opposite effect was
      observed in girls (0.48+/-0.19 vs 0.09+/-0.05, P<0.05). In genotype-phenotype
      associations in obese children, the polymorphism did not affect parameters of
      insulin, glucose, or lipid metabolism in the whole population. Again, however,
      obese boys with Ile/Val genotype had significantly higher high-density
      lipoprotein (HDL) cholesterol levels (1.46+/-0.07 vs 1.23+/-0.03 mmol/l, P<0.05).
      CONCLUSION: In conclusion, our findings suggest a sex-specific protective effect
      of the Val1483Ile polymorphism in FAS for obesity in Caucasian boys. In addition,
      the polymorphism may be associated with a beneficial lipid profile in obese boys.

PMID- 16788567
TI  - Four-week pedometer-determined activity patterns in normal weight and overweight
      UK adults.
AB  - OBJECTIVE: To assess pedometer-determined physical activity levels and activity
      patterns in a sample of free-living normal weight and overweight UK adults.
      DESIGN: Pedometer-based 4-week observational study. PARTICIPANTS: One hundred and
      twenty-two healthy participants, recruited from two regions in the UK, classified
      as normal weight (33 females and 26 males) or overweight (31 females and 32
      males), in the age range of 18 to 65 years, completed the study. MEASUREMENTS:
      Daily step counts were measured using a Yamax SW-200 pedometer, and were then
      recorded in an activity log. Comparisons were made between activity patterns
      occurring over different days of the week for the normal weight and overweight
      groups. Measurements of height, weight and percentage body fat, by bioelectrical
      impedance, were taken pre- and post-study. RESULTS: A consistent reduction in
      activity was observed on a Sunday in the overweight group, and mean daily step
      counts accumulated on Sundays were significantly lower, by an average of 2221
      steps/day, when compared with all other days of the week (all P<0.001). In
      comparison, no day-of-the-week effect was observed in the normal weight group.
      Mean step counts reported on each day of the week did not differ significantly
      between the two groups, with the exception of Sunday when the overweight group
      reported significantly fewer steps than the normal weight participants (8093
      versus 10 538, P<0.001). CONCLUSIONS: Activity levels dropped dramatically in the
      sample of overweight adults on a Sunday. Simple instructions to at-risk
      individuals, to increase their general activity levels on a Sunday, via general
      practitioners and public health messages could prove to be a subtle, but
      effective, strategy to tackle obesity.

PMID- 16788568
TI  - Dual energy X-ray absorptiometry body composition and aging in a population-based
      older cohort.
AB  - OBJECTIVE: The aims of this cross-sectional study were (1) to examine the effect
      of age on body composition in older adults using dual-energy X-ray absorptiometry
      (DXA) and (2) to evaluate the agreement of DXA with standard indirect
      anthropometric measures (body mass index (BMI), waist circumference and waist-to
      hip ratio (WHR)). RESEARCH METHODS AND PROCEDURES: A population-based sample of
      731 adults aged between 50 and 79 years underwent measurement of BMI, waist
      circumference, WHR, DXA total body fat mass, DXA % total body fat, DXA % trunk
      fat and DXA lean body mass. Linear regression was used to test for trend in
      measures of body composition between age categories in men and women. Partial
      correlations and Bland-Altman analysis were used to examine the agreement of DXA
      measures with indirect measures. RESULTS: DXA lean body mass decreased
      significantly with increasing age in both sexes (P<0.05). In males, BMI (P=0.01)
      and body weight (P<0.01) decreased with age, and in females, WHR (P=0.05), DXA %
      total fat (P=0.02) and DXA % trunk fat (P=0.05) increased with age. There was
      good agreement between DXA measures of fatness and indirect anthropometric
      measures, except for WHR, which showed greater variability in its comparisons
      with DXA. CONCLUSION: Using the highly sensitive and direct DXA method of
      measuring body composition, a decline in lean body mass and an increase in
      adiposity was observed with aging. Except for WHR, indirect anthropometric
      measures generally showed high levels of agreement with DXA fat measures in this
      older cohort.

PMID- 16788569
TI  - Trends in the distribution of body mass index among Chinese adults, aged 20-45
      years (1989-2000).
AB  - OBJECTIVE: To describe body mass index (BMI, in kg/m(2)) distribution patterns
      and trends among Chinese adults, aged 20-45 years (1989-2000). DESIGN: A
      descriptive, population-based study of BMI change. SETTING: Chinese provinces
      (eight in 1989 and 1997; nine in 2000), representative of the household-based
      surveys (the China Health and Nutrition Survey, 1989-2000) using multistage,
      random cluster sampling, supplemented with annual household consumption survey
      data of the State Statistical Bureau (SSB). SUBJECTS: A total of 4527, 4507 and
      4046 adults, aged 20-45 years, in 1989, 1997 and 2000, respectively.
      MEASUREMENTS: BMI (underweight: BMI<18.5 kg/m(2) and overweight: BMI>/=25
      kg/m(2)). Percentile curves for BMI in 1989 and 2000 were constructed by gender
      and age using the LMS (lambda, mu, sigma) method. RESULTS: Compared with 1989,
      the 2000 BMI distribution curves flattened at higher levels of BMI (men and
      women). There was a 13.7% increase in the proportion of men and a 7.9% increase
      of women who were overweight or obese with a resulting greater change in the
      annualized prevalence rate for men. This increase in the prevalence of overweight
      and obesity was far greater than the decrease (2.1% for men; 2.2% for women) in
      that of underweight. Age-gender-specific percentile curves showed BMI increases
      mainly among women, aged 35-45 years, and among men at all age groups.
      CONCLUSIONS: Chinese BMI dynamics show much greater rates of change among men,
      aged 20-45 years, than among women, with the increase among women concentrated
      between ages 35 and 45 years. These changes portend large shifts in other diet
      related non-communicable diseases in China over the following decades.
      Controlling the increasing trends of BMI, especially in men, is an important
      public health problem facing China.

PMID- 16788570
TI  - Assessing social differences in overweight among 15- to 16-year-old ethnic
      Norwegians from Oslo by register data and adolescent self-reported measures of
      socio-economic status.
AB  - OBJECTIVE: To determine to what extent self-reported and objective data on socio
      economic status (SES) are associated with overweight/obesity among 15 to 16-year
      old ethnic Norwegians. DESIGN: A cross-sectional questionnaire study on health
      and health-related behaviors. SUBJECTS: All school children aged 15-16 years old
      in 2000 and 2001 in Oslo, Norway. Response rate 88% (n=7343). This article is
      based on the data from the 5498 ethnic Norwegians. MEASUREMENTS: Self-reported
      height and weight were used to measure overweight (including obesity) as defined
      by the International Obesity Task Force cutoffs at the nearest half-year
      intervals. SES was determined by register data from Statistics Norway on
      residential area, parental education and income and by adolescent self-reported
      measures on parental occupation and adolescents' educational plans. RESULTS: The
      prevalence of overweight/obesity was low, but higher among boys (11%) than among
      girls (6%). Parental education (four levels) showed the clearest inverse
      gradients with overweight/obesity (boys: 18, 13, 10 and 7%; girls: 11, 6, 6 and
      4%). Parental education remained significantly associated with overweight/obesity
      when adding occupation and income to the model for the boys, whereas there were
      no significant associations in the final model for the girls. Overweight/obesity
      was associated with a lower odds ratio of planning for higher education
      (college/university) among boys only. CONCLUSION: For the boys, parental
      education was most strongly associated with overweight/obesity, and the
      association between overweight/obesity and educational plans appears to imply
      downward social mobility. The relationships between the various SES measures and
      overweight/obesity appeared more interrelated for the girls.

PMID- 16788571
TI  - Comparison of ultrasonographic and anthropometric methods to assess body fat in
      childhood obesity.
AB  - BACKGROUND: Pattern of fat distribution rather than obesity is of importance for
      cardiovascular morbidity and mortality. The accurate measurement of total and
      regional fat mass requires sophisticated and often expensive methods that have
      limited applicability in the clinical setting. OBJECTIVE: The aim of this study
      is to evaluate body fat distributions by ultrasound (US) as a gold standard
      method for measuring visceral, preperitoneal and subcutaneous fat layers and
      comparing with anthropometric results, and then to find the most reliable
      anthropometric measurement in childhood obesity. MATERIALS AND METHODS: Study
      group of 51 obese children (21 F, 30 M) (mean age+/-s.d.: 11.5+/-2.6 years) and
      control group of 33 non-obese children (17 F, 16 M) (mean age+/-s.d.: 12.2+/-2.7
      years) were recruited for this study. Anthropometric measurements as body mass
      index (BMI), waist circumference (WC), waist/hip ratio (WHR), triceps and
      subscapular skinfold thicknesses were taken from all the participants. Abdominal
      preperitoneal (P), subcutaneous (S) fat at their maximum (max) and minimum (min)
      thickness sites, visceral (V), triceps (TrUS) and subscapular (SsUS) fat
      thicknesses were also measured ultrasonographically. RESULTS: In the obese group,
      BMI was significantly correlated with US measurements of fat thicknesses, except
      Pmin and SsUS, whereas in the control group, BMI was significantly correlated
      with all US fat measurements. The relation of US measurements with skinfold
      thickness and WC was more significant in the control than in the obese group. No
      relation between WHR and US fat thickness measurements was found in both groups.
      Multiple regression analysis, using V as the dependent variable and
      anthropometric parameters, gender and the group as the independent variables,
      revealed BMI was the best single predictor of V (R(2): 0.53). CONCLUSION: This
      study suggests that the validity of the anthropometric skinfold thickness in the
      obese children is low. Despite the limitations reported in the literature, in our
      study, BMI provides the best estimate of body fat. WHR in children and
      adolescents is not a good index to show intra-abdominal fat deposition.

PMID- 16788572
TI  - Skeletal myogenesis by human embryonic stem cells.
AB  - We have examined the myogenic potential of human embryonic stem (hES) cells in a
      xeno-transplantation animal model. Here we show that precursors differentiated
      from hES cells can undergo myogenesis in an adult environment and give rise to a
      range of cell types in the myogenic lineage. This study provides direct evidences
      that hES cells can regenerate both muscle and satellite cells in vivo and are
      another promising cell type for treating muscle degenerative disorders in
      addition to other myogenic cell types.

PMID- 16788573
TI  - Glycogen synthase kinase-3beta positively regulates the proliferation of human
      ovarian cancer cells.
AB  - Although glycogen synthase kinase-3 (GSK-3) might act as a tumor suppressor since
      its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK
      3beta may contribute to NF-kappaB activation in cancer cells leading to increased
      cancer cell proliferation and survival. Here we report that GSK-3beta activity
      was involved in the proliferation of human ovarian cancer cell both in vitro and
      in vivo. Inhibition of GSK-3 activity by pharmacological inhibitors suppressed
      proliferation of the ovarian cancer cells. Overexpressing constitutively active
      form of GSK-3beta induced entry into the S phase, increased cyclin D1 expression
      and facilitated the proliferation of ovarian cancer cells. Furthermore, GSK-3
      inhibition prevented the formation of the tumor in nude mice generated by the
      inoculation of human ovarian cancer cells. Our findings thus suggest that GSK
      3beta activity is important for the proliferation of ovarian cancer cells,
      implicating this kinase as a potential therapeutic target in ovarian cancer.

PMID- 16788596
TI  - Bringing metabolomics data into the forefront of systems biology.

PMID- 16788595
TI  - Putative regulatory sites unraveled by network-embedded thermodynamic analysis of
      metabolome data.
AB  - As one of the most recent members of the omics family, large-scale quantitative
      metabolomics data are currently complementing our systems biology data pool and
      offer the chance to integrate the metabolite level into the functional analysis
      of cellular networks. Network-embedded thermodynamic analysis (NET analysis) is
      presented as a framework for mechanistic and model-based analysis of these data.
      By coupling the data to an operating metabolic network via the second law of
      thermodynamics and the metabolites' Gibbs energies of formation, NET analysis
      allows inferring functional principles from quantitative metabolite data; for
      example it identifies reactions that are subject to active allosteric or genetic
      regulation as exemplified with quantitative metabolite data from Escherichia coli
      and Saccharomyces cerevisiae. Moreover, the optimization framework of NET
      analysis was demonstrated to be a valuable tool to systematically investigate
      data sets for consistency, for the extension of sub-omic metabolome data sets and
      for resolving intracompartmental concentrations from cell-averaged metabolome
      data. Without requiring any kind of kinetic modeling, NET analysis represents a
      perfectly scalable and unbiased approach to uncover insights from quantitative
      metabolome data.

PMID- 16788615
TI  - Psoriasis vulgaris: a genetic approach.
AB  - Evidence for a genetic contribution in psoriasis comes from direct examination of
      a large segment of the population in an isolated island environment,
      epidemiologic and questionnaire studies presented to psoriatic patients, twin
      studies collected from the literature and from twin registries, and splitsibship
      analysis. The concordance of psoriasis in monozygotic twins was 65-72%, whereas
      psoriasis in dizygotic twins was 15-30%. Determination of concordance in older
      twin pairs from a national twin registry in Denmark revealed nearly 90-100%
      heritability. In order to link psoriasis with known markers within the human
      genome, serologic studies have been carried out with a variety of blood group and
      polymorphic protein antigens. A weak association with the MNS and Lewis Blood
      Groups Systems (relative risk, 3.5) has been identified. Stronger associations
      with class I B locus and class II D locus genes (relative risk, 8-12) have also
      been determined by studies of the human lymphocyte-antigen system. Finally, a
      strong association with HLA Cw6 has been determined; this marker is thought to be
      in linkage disequilibrium with B and D locus genes previously associated with
      psoriasis. The relative risk of developing psoriasis in HLA Cw6 positive
      individuals is about 24. A few large kindred have been reported in the
      dermatology literature. These support the hypothesis of autosomal dominant
      inheritance with penetrance of approximately 60%. In cooperation with The
      National Psoriasis Foundation, we have now identified over 90 families with
      psoriasis in three generations. We have begun the process of ascertainment, the
      construction of family trees, and the collection of leukocyte DNA for linkage
      analysis with established restriction fragment polymorphisms (RFLP). Our initial
      assessment is being directed to four RFLP that span approximately 30 centiMorgans
      of the short arm of human chromosome 6. Although karyotyping is uncommonly done
      in patients because of psoriasis, we now seek evidence of translocation of
      chromosome 6 in association with psoriasis.

PMID- 16788616
TI  - Psoriasis: the application of genetic technology and mapping.
AB  - Recent progress in molecular genetics has led to the creation of a map of the
      human genome utilizing RFLP. Given a sufficient family structure, genetic
      diseases can now be placed on this map. Genetic studies of psoriasis can both
      help resolve and be confounded by problems of disease heterogeneity,
      environmental effects on disease expression, and lack of a clear mode of
      inheritance.

PMID- 16788618
TI  - Epidermal growth factor/transforming growth factor alpha receptors and psoriasis.
AB  - The abnormal growth and differentiation in psoriasis is reflected in the abnormal
      regulation of Epidermal Growth Factor/Transforming Growth Factor Alpha
      (EGF/TGFalpha) receptor metabolism. In psoriasis and other hyperproliferative
      skin conditions these receptors are persistently expressed throughout the
      interfollicular epidermis as long as the growth stimulatory signal persists. One
      of the first biochemical signs of effective therapy of psoriasis is the return of
      the EGF/TGFalpha receptor pattern toward the primarily basilar distribution seen
      in normal human adult skin. Whether the abnormal expression of TGFalpha in the
      involved skin induces the persistent expression of EGF receptors is not known nor
      is the signal that causes the increased production of TGFalpha. Studies to
      determine what factors regulate EGF receptor expression and TGFalpha induction
      may yield important new insights into the pathogenesis and therapy of psoriasis.

PMID- 16788617
TI  - Growth factor and proto-oncogene expression in psoriasis.
AB  - The expression of several proto-oncogenes and growth factors was analyzed in
      normal skin and psoriatic lesions by RNA blot hybridization. Isolation of intact
      RNA from frozen biopsy samples required immediate exposure to denaturants during
      tissue homogenization. Lipocortin II and cyclophilin transcripts were used as
      internal controls. These transcripts were abundant and slightly but significantly
      elevated in psoriatic lesions. When results were normalized according to these
      reference transcripts, there was no increase in the expression of c-myc, c-Ha
      ras, c-erbB (EGF receptor), c-jun, or transforming growth factor-beta (TGF-beta)
      transcripts in psoriatic lesions, and lesional c-fos transcripts were decreased
      relative to normal skin. In contrast, expression of TGF-alpha mRNA transcripts
      were markedly increased in psoriatic lesions even after normalization. Placement
      of normal or psoriatic tissue in organ culture for 2 to 4 h resulted in strong
      induction of c-fos, c-jun, and c-myc transcripts, but not of the other genes
      studied. Thus, overexpression of proto-oncogenes may be more characteristic of
      the epidermal response to acute injury than of the steady-state hyperplasia
      characteristic of psoriasis. Interferon-gamma (IFN-gamma) increased TGF-alpha
      mRNA levels in cultured human KC at long time intervals (24-48 h). However, of
      various cytokines tested, only EGF and TGF-alpha induced TGF-alpha mRNA after
      short time intervals (2-4 h). These results as well as the selective
      overabundance of TGF-alpha mRNA in psoriatic lesions among various cytokines
      tested suggest that activation of the EGF receptor tyrosine kinase by TGF-alpha
      is important in the pathogenesis of psoriatic epidermal hyperplasia.

PMID- 16788619
TI  - Tissue plasminogen activator in psoriasis.
AB  - Elevated levels of the serine proteinase plasminogen activator are observed in
      psoriatic lesions. In contrast to normal epidermis, lesional psoriatic epidermis
      contains primarily tissue type plasminogen activator (tPA) activity and much
      lower levels of urokinase type plasminogen activator (uPA) activity. Tissue
      plasminogen activator is also detectable immunocytochemically in lesional
      psoriatic but not normal epidermis. Similarly, mRNA for tPA is observed in
      lesional epidermis only. These results suggest that lesional psoriatic epidermis
      synthesizes enhanced levels of tPA compared to normal. Additional data support
      the hypothesis that enhanced tPA may be another marker common to psoriatic
      epidermis, epidermis during wound repair, and keratinocytes in culture. The
      significance of elevated tPA in psoriatic lesions is presently unclear, but its
      possible relationship to epidermal proliferation and cutaneous inflammation is
      under study.

PMID- 16788620
TI  - Phosphoinositide-mediated signal transduction in normal and psoriatic epidermis.

PMID- 16788621
TI  - Immunologic mechanisms in psoriasis.
AB  - The demonstration of activated T lymphocytes, HLA-DR+ I-CAM 1+, gamma IP-10+
      keratinocytes, and increased levels of lymphokines in active plaques suggests
      that immunologic mechanisms may play a role in the pathogenesis of psoriasis.
      Epidermal hyperplasia and inflammation in psoriasis may be linked by those
      cytokines many of which are produced by both keratinocytes and leukocytes.
      Epidermal acanthosis and keratinocyte mitoses have been observed in delayed-type
      hypersensitivity reactions and after the intradermal injection of gamma
      interferon. Gamma interferon and its induced proteins have been demonstrated in
      active psoriatic plaques. Increased levels of the keratinocyte autocrine
      cytokines, transforming growth factor (TGF)-alpha and interleukin (IL)-6, have
      been detected in active plaques. The apparent overexpression of IL-6 in
      hyperplastic psoriatic tissue may explain features of psoriasis that link
      keratinocyte proliferation with immune activation and tissue inflammation. Both
      IL-6 and gamma interferon increased TGF-alpha expression in normal cultured
      keratinocytes. Cytokines produced during immune activation and other inflammatory
      processes may lead to epidermal hyperplasia.

PMID- 16788622
TI  - Speculations on the immunopathogenesis of psoriasis: T-cell violation of a
      keratinocyte sphere of influence.
AB  - The thesis is advanced that the differences in antigen processing and
      presentation described for "fresh" and "cultured" Langerhans cells in vitro
      reflect similar differences between intraepidermal and intranodal Langerhans
      cells in vivo. The functional properties of Langerhans cells are dependent upon
      the microenvironment in which they reside; thus, intraepidermal Langerhans cells
      are under the influence of cytokines secreted by keratinocytes, whereas
      intranodal Langerhans cells come under the influence of lymphokines from T
      lymphocytes. It is speculated that a genetic lesion in psoriasis robs
      keratinocytes of their capacity to create an "appropriate" epidermal
      microenvironment. As a consequence, intraepidermal Langerhans cells adopt the
      functional program of intranodal cells. When "uninvolved" psoriatic skin receives
      a cutaneous challenge with antigen, Langerhans cells, by activating naive T cells
      in situ, unwittingly engender a microenvironment that is more appropriate to a
      lymph node. This skin becomes "involved" as it gradually acquires features
      associated with lymph nodes (such as high endothelial venules). And the
      derangement is further complicated by abnormalities of proliferation and
      differentiation among keratinocytes and dermal fibroblasts as they respond to the
      inappropriate T-cell-derived lymphokines, giving rising to the typical, active
      psoriatic lesion.

PMID- 16788623
TI  - Lymphocyte chemoattractants in psoriasis and normal skin.
AB  - The local production of lymphocyte attractants may influence both physiologic
      lymphocyte trafficking in the skin as well as the infiltration of these cells in
      pathologic states. Recent evidence for the production of acidic lipid lymphocyte
      chemoattractants, particularly 12[R]-hydroxyeicosatetraenoic acid, in psoriatic
      lesions is reviewed. Water extractable lymphocyte attractant activity may also be
      recovered from both normal skin samples and psoriatic lesional stratum corneum,
      and may be important in the pathophysiology of lymphocyte trafficking. Less than
      10 kD activity from normal skin has undergone the most detailed characterization.
      This has led to the isolation of a novel, as yet unidentified compound from
      normal skin, which we have termed "plasma-associated lymphocyte chemoattractant"
      (PALC).

PMID- 16788625
TI  - The role of epidermal cytokines in inflammatory skin diseases.
AB  - Cytokines (hormone-like polypeptide mediators) play a major role in inflammatory
      and immunoregulatory responses. Skin, and particularly keratinocytes in the skin,
      represent a potent source for many cytokines, including interleukins 1, 6, 8, and
      the hemopoietic colony stimulating factors. Cytokines initiate their biologic
      action by interacting with target cells bearing cytokine receptors and then
      initiating a cascade of cellular interactions. Certain inflammatory skin diseases
      have been associated with overproduction of cytokines, alteration in cytokine
      receptors, or dysregulation of cytokines. While data is still quite preliminary,
      it is likely that cytokines contribute to the pathogenesis of many inflammatory
      skin diseases.

PMID- 16788624
TI  - Interleukin-1 in human skin: dysregulation in psoriasis.
AB  - Cytokine dysregulation is an attractive concept to explain many of the observed
      abnormalities in psoriasis. IL-1, in particular, can potentiate immune cellular
      activation, activate fibroblasts, and increase endothelial cell adhesiveness to
      leukocytes. Here, we review IL-1 regulation in normal and psoriatic skin in vivo
      in relation to normal skin and cultured keratinocytes. Contrary to expectations,
      IL-1 functional activity in psoriatic lesions is reduced, not increased, relative
      to normal skin. The reduction is attributable to the presence of IL-1 inhibitors,
      reduced IL-1alpha levels, and an IL-1beta that lacked function in T-cell assays.
      IL-1beta protein is actually significantly increased in psoriatic lesions, but
      the mechanism of its non-functionality remains unclear. Unlike cultured
      keratinocytes, which accumulate large, inactive IL-1beta precursors, both normal
      and psoriatic skin process IL-1beta to a mature form. Novel mechanisms of post
      translational processing by epidermis in vivo may generate a novel form of IL
      1beta with unknown functions. The marked abnormalities of IL-1 regulation in
      psoriatic skin suggest that this molecule may be important in normal skin
      homeostasis.

PMID- 16788626
TI  - Lymphocyte adhesion to psoriatic dermal endothelium: mechanism and modulation.
AB  - Psoriasis is characterized by the hyperproliferation of keratinocytes in the
      epidermis and the accumulation of activated CD4+ T lymphocytes in the upper
      dermis. We have recently rested the hypothesis that the abnormal endothelial
      proliferation in the dermal papillae of psoriatic lesions may be mechanistically
      linked to the expression of endothelial ligands capable of promoting lymphocytes
      binding and extravasation. The results indicated that specialized endothelial
      cells lining the post-capillary venules of psoriatic lesions are capable of
      promoting the selective adherence of human CD4+ T cells and its memory subset. In
      contrast, B cells, CD8+ T cells, and CD45RA+ T cells are deficient in their
      capacities to bind. The adhesion process is energy and calcium dependent and
      involves tissue-specific lymphocyte receptors, with LFA-1 molecules playing an
      accessory role. We concluded that transformation of the dermal endothelium into a
      lymphocyte-receptive phenotype by defined growth factors or cytokines may
      represent a positive feedback mechanism promoting lymphocyte migration into the
      diseased sites.

PMID- 16788627
TI  - The role of immune system in the pathogenesis of psoriasis.
AB  - Psoriatic involved skin contains an increased number of activated T cells. The
      mechanism through which these T cells achieve and maintain their activated state
      is unknown, and both antigen-dependent and -independent mechanisms may
      contribute. Recently a novel pathway of antigen-independent T-cell activation has
      been described. This pathway is identified by a monoclonal antibody that binds to
      a T-cell membrane surface molecule termed "UM4D4." This molecule is expressed on
      a minority (20%) of psoriatic peripheral blood T cells but on a majority (75%) of
      the T cells in lesional skin. Thus, UM4D4 could play a role in antigen
      independent T-cell activation in psoriasis. Indeed the monoclonal antibody anti
      UM4D4 consistently induces proliferation of psoriatic UM4D4+ T-cell clones. The
      activity of antigen-dependent pathways are also enhanced in psoriatic epidermis
      in as much as involved skin relative to uninvolved skin contains an increased
      number and function of antigen-presenting cells. Upon activation, the lesional T
      cells release lymphokines. Central to the immune hypothesis of psoriasis is that
      some of these T-cell lymphokines act on keratinocytes to induce changes
      characteristic of psoriasis. Indeed lymphokines from lesional psoriatic T-cell
      clones directly alter in vitro keratinocyte phenotype through induction of
      intercellular adhesion molecule-I (ICAM-1) and HLA-DR cell-surface expression.
      Furthermore, the lymphokines also enhance keratinocyte growth. These data suggest
      a critical role for the immune system in the pathogenesis of psoriasis.

PMID- 16788628
TI  - Lymphocyte trafficking in psoriasis: a new perspective emphasizing the dermal
      dendrocyte with active dermal recruitment mediated via endothelial cells followed
      by intra-epidermal T-cell activation.
AB  - Prominent within the inflammatory infiltrate of psoriasis are HLA-DR positive T
      lymphocytes and factor XIIIa positive dermal dendrocytes. Many investigators
      studying psoriasis have assumed that the HLA-DR positive T cells are activated,
      and thereby capable of producing lymphokines such as gamma interferon. However,
      by immunohistochemical analysis, greater than 95% of the dermal T cells in
      psoriatic lesions are Ki-67 negative, which suggests that they are in a resting
      or non-cycling (Go) state. In contrast to the dermal T-cell population, the
      epidermal T-cell population contains a greater population of Ki-67 positive
      lymphocytes. The entry of the T cells into the epidermis is, therefore,
      apparently associated with an important activation event, which in all likelihood
      involves interaction with the keratinocyte. The presence of activated
      intraepidermal T cells has been substantiated by the ability to detect gamma
      interferon mRNA by polymerase chain reaction in epidermal sheets of psoriatic
      lesions. The pathophysiologic implication in psoriasis for these distinctions and
      compartmentalization involving dermal and epidermal T cells are placed into the
      context of a cascade of cellular trafficking events, which are further dissected
      into a specific network of molecular mediators of inflammation. This report
      suggests that more attention should be placed on the microenvironment of the
      skin, with specific emphasis on the mechanism by which T cells accumulate in the
      dermis and epidermis, and elucidation of the selective inductive and recruitment
      capabilities of endothelial cells, perivascular dermal dendrocytes, and
      keratinocytes.

PMID- 16788629
TI  - Immunology of AIDS related to psoriasis.
AB  - The association of severe psoriasis with HIV infection, which dysregulates and
      destroys the human immune system, supports the hypothesis that psoriasis is an
      immunologically mediated disease. Psoriasis and Kaposi's sarcoma share
      angiogenesis as basic early findings and could both be caused by differential
      cytokine expression or responsiveness. AIDS and research models including
      transgenic mice offer new models in which to study the role of the immune system
      and specific gene products in the pathogenesis of psoriasis and other skin
      diseases.

PMID- 16788630
TI  - The expression of retrovirus-like particles in psoriasis.
AB  - Retrovirus-like particles have been isolated from patients with psoriasis.
      Antigens crossreacting with the major internal proteins pso p27, of these
      particles have been demonstrated in the wall of dermal vessels and in a
      subfraction of cells in psoriatic lesions. The antigen has also been observed in
      blood lymphocytes from psoriatic patients. Pso p27 antigen and anti-pso p27
      antibodies are present as complement-activating immune complexes in psoriatic
      scale and in the blood of patients with psoriasis and psoriatic arthritis. The
      potential contribution of the circulating immune complexes to the inflammatory
      process in psoriasis is discussed.

PMID- 16788631
TI  - Multi-stage program of differentiation in human epidermal keratinocytes:
      regulation by retinoids.
AB  - The proliferation and differentiation of epidermal keratinocytes in vivo and in
      vitro is influenced by a variety of different factors, including several peptide
      growth factors, protein kinase C activators, retinoids, and various cytokines.
      Retinoids can affect the proliferation of human epidermal keratinocytes either
      positively or negatively and influence the multi-step program of differentiation
      in epidermal keratinocytes at very specific stages. Epidermal keratinocytes
      express nuclear retinoic acid receptors, RARalpha, and RARgamma. It is likely
      that at least some of the alterations in gene expression induced by retinoids are
      mediated through these RAR. The cytosolic retinoic acid-binding protein (CRABP),
      which is differentially expressed during squamous differentiation of human
      epidermal keratinocytes, may control the effective concentration of retinoic acid
      in the cell and therefore regulate indirectly gene expression.

PMID- 16788632
TI  - Metabolism of natural retinoids in psoriatic epidermis.
AB  - Synthetic retinoids that have distinct therapeutic activity on psoriatic plaques
      act at least in part through the metabolic pathways of natural retinoids. The
      metabolism of retinol, retinal, and retinoic acid in human epidermis in general
      and psoriatic plaques in particular has not been previously analyzed. This
      appears to be an important issue, because enzymatic formation of retinoic acid
      from retinol within target cells is thought to be the source of biologically
      active retinoic acid therein and might be subjected to regulation. We found chat
      the enzymatic system that transforms (3H)retinol into (3H)retinoic acid is
      detectable in psoriatic plaques (0.33 +/- 0.07 pmol/h/mg protein) but only in
      trace amounts in normal epidermis. The activity due to alcohol deshydrogenase
      seems not to be involved in this process. (3H)retinal was found to be either
      reduced into retinol or oxidized into retinoic acid, depending on the ratio of
      NAD to NADH (the oxidized arid reduced nicotinamide-adenine dinucleotide,
      respectively); the former reaction was higher in psoriatic plaques than in normal
      epidermis.

PMID- 16788633
TI  - Cytotoxic and immunologic effects of methotrexate in psoriasis.
AB  - Based on recent experience that Cyclosporin A, an immunosuppressive drug,
      produces marked improvement in psoriasis, possible immunomodulatory activities of
      methotrexate (MTX) have been reviewed to look for alternate mechanisms of MTX
      action in psoriasis. It is generally considered that the therapeutic results of
      MTX in psoriasis are related to a direct effect on epidermal cell hyperplasia
      through inhibition of DNA synthesis. Several studies in the literature now
      suggest possible effects of MTX on the immune system of psoriatics as well as in
      animal models that may have some pathogenic similarities to psoriasis. In
      psoriatics receiving MTX, neutrophil chemotaxis is suppressed, resulting in a
      possible alteration in the potential pathologic activity of neutrophils commonly
      found in lesional skin. MTX does improve both psoriatic and rheumatoid arthritis.
      Animal studies of the latter using adjuvant arthritis and graft vs host disease
      (GVHD) have indicated several possible mechanisms for MTX that affect these
      processes. In GVHD, MTX selectively destroys cycling CD8+ cells, and in adjuvant
      arthritis the activation of macrophages is prevented by inhibition of T-cell
      function. While MTX generally has not been clinically utilized as an
      immunomodulatory drug for immunologically related diseases, it may, nonetheless,
      have selective actions that could be specific for some diseases. MTX and
      Cyclosporin A could work mechanistically in similar ways but at different steps
      in the activation of T cells and macrophages. It may be that the major direct
      effect of MTX on epidermal cell proliferation is complemented or even mediated by
      subtle immunoregulatory effects on the melange of cells in the affected skin and
      the systemic immune response.

PMID- 16788635
TI  - Experimental models for psoriasis.
AB  - Evidence suggests that inherent in skin of psoriatic subjects are cells,
      architectural structures, and/or mediators, which are, at a minimum, responsible
      for its hyperproliferative epidermis. An objective of our laboratory has been to
      establish an in vitro definition of this inherent aberration. Fibroblasts are
      important to epidermal proliferation/differentiation. This, and an unconfirmed
      report that fibroblasts from psoriatic subjects might drive the abnormal
      epidermal proliferation in psoriasis, have caused further focus on the
      fibroblast. Data show that fibroblasts from patients with psoriasis, both
      involved and uninvolved, in the presence of human serum, either normal or
      psoriatic, have an increased rate of proliferation. Fibroblasts from uninvolved
      psoriatic sites are most responsive. To determine if fibroblasts from psoriatics
      could induce the psoriasiform phenotype on normal keratinocytes, an interactive
      skin equivalent system has been developed. With this system, fibroblasts from
      uninvolved and involved sites cause normal keratinocytes to have an enhanced
      outgrowth. Uninvolved fibroblasts cause the greatest changes. The nature of the
      skin equivalent system calls for this to occur via message over distance. We
      conclude that fibroblasts from psoriatic subjects can induce a psoriasiform
      phenotype via a soluble message.

PMID- 16788634
TI  - Cyclosporine A in the treatment of psoriasis: a clinical and mechanistic
      perspective.
AB  - Cyclosporine A, a unique immunomodulatory agent, has been used increasingly over
      the last 5 years in the management of severe psoriasis. The remarkable efficacy
      of this drug coupled with its known immunosuppressive properties have enabled a
      further appreciation of the role of the immune system in the induction and
      maintenance of psoriatic plaques. Although acting primarily on T lymphocytes,
      there is also evidence for an effect of cyclosporine A on other constitutive cell
      types within the skin. The future use of systemically administered cyclosporine A
      in the treatment of psoriasis and other cutaneous diseases is dependent on the
      successful balance of efficacy and side-effect profile; namely, the dose-related
      problems of hypertension and nephrotoxicity. As a result of the toxicity
      encountered with systemically administered cyclosporine A, attempts to formulate
      a successful topical preparation for use in cutaneous disease are being made. The
      advent of cyclosporine A provides the dermatologist with a new therapeutic
      strategem in the management of psoriasis, although the long-term safety of such
      interventional therapy remains to be discerned.

PMID- 16788637
TI  - Inherited mouse mutations as models of human adnexal, cornification, and
      papulosquamous dermatoses.
AB  - Nearly 100 mouse mutations have been described as causing some type of
      abnormality of the skin or hair. As only a few of these mutations have been
      studied in detail, they remain an untapped resource for furthering knowledge of
      basic cutaneous physiology and understanding the pathophysiology of analogous
      diseases in humans. Several diverse murine mutations are discussed. These include
      "asebia," a mildly hyperkeratotic disorder with sebaceous gland hypoplasia;
      "ichthyosis," an example of abnormal hair growth associated with hyperkeratosis;
      "rhino" and "hairless," two related examples of congenital follicular
      malformations; and "flaky skin", a potential animal model of eruptive psoriasis.

PMID- 16788636
TI  - Targeting gene expression to the epidermis of transgenic mice: potential
      applications to genetic skin disorders.
AB  - The ability to specifically target gene expression to the epidermis of transgenic
      mice offers the exciting possibility of creating animal models of certain skin
      disorders that are inherited in man. It may be possible to produce mouse models
      of dominantly inherited keratinization disorders by targeting the expression of
      mutant genes encoding the major differentiation products of the epidermis, such
      as the differentiation specific keratins, filaggrin and cell envelope proteins.
      Mouse models for other skin disorders associated with abnormal regulation of
      growth, such as psoriasis, may be generated by targeting the overexpression of
      cytokines and growth factors, which are thought to play important roles in the
      pathogenesis of this disease. The development of currently unavailable animal
      models for certain inherited human skin diseases would not only contribute to our
      understanding of the pathogenesis of these diseases at the molecular level, but
      also provide interesting models for therapeutic intervention.

PMID- 16788679
TI  - Is the risk of acute lymphoblastic leukemia reduced in siblings to children with
      the disease? A novel hypothesis explored by international collaboration.

PMID- 16788682
TI  - Allogeneic haematopoietic stem cell transplantation for severe autoimmune
      diseases: great expectations but controversial evidence.

PMID- 16788681
TI  - Agreement of pesticide biomarkers between morning void and 24-h urine samples
      from farmers and their children.
AB  - In pesticide biomonitoring studies, researchers typically collect either single
      voids or daily (24-h) urine samples. Collection of 24-h urine samples is
      considered the "gold-standard", but this method places a high burden on study
      volunteers, requires greater resources, and may result in misclassification of
      exposure or underestimation of dose due to noncompliance with urine collection
      protocols. To evaluate the potential measurement error introduced by single void
      samples, we present an analysis of exposure and dose for two commonly used
      pesticides based on single morning void (MV) and 24-h urine collections in
      farmers and farm children. The agreement between the MV concentration and its
      corresponding 24-h concentration was analyzed using simple graphical and
      statistical techniques and risk assessment methodology. A consistent bias towards
      overprediction of pesticide concentration was found among the MVs, likely in
      large part due to the pharmacokinetic time course of the analytes in urine. These
      results suggest that the use of single voids can either over- or under-estimate
      daily exposure if recent pesticide applications have occurred. This held true for
      both farmers as well as farm children, who were not directly exposed to the
      applications. As a result, single void samples influenced the number of children
      exposed to chlorpyrifos whose daily dose estimates were above levels of
      toxicologic significance. In populations where fluctuations in pesticide exposure
      are expected (e.g., farm families), the pharmacokinetics of the pesticide and the
      timing of exposure events and urine collection must be understood when relying on
      single voids as a surrogate for longer time-frames of exposure.

PMID- 16788683
TI  - Evaluation of the COBAS Amplicor HCMV Monitor for early detection and monitoring
      of human cytomegalovirus infection after allogeneic stem cell transplantation.
AB  - Early diagnosis of human cytomegalovirus (HCMV) infection and the introduction of
      preemptive antiviral therapy have reduced HCMV-related mortality after allogeneic
      stem cell transplantation. A critical goal remains stratifying risk profiles and
      minimizing potential harm owing to antiviral overtreatment. We compared the
      commercially available standardized COBAS Amplicor CMV Monitor (CACM) to an in
      house PCR assay, for the monitoring of HCMV infection. Seventy-two patients were
      surveyed by an in-house PCR of whole blood, quantitative viral load assessment by
      CACM and virus culture assays in a prospective and a retrospective study. A high
      concordance between CACM and PCR was documented. The viral load at onset
      correlated with the peak viral load (Spearman rank correlation R=0.634,
      P=0.0004). In patients developing HCMV disease, both viral loads were in trend
      higher (P=0.823, respectively P=0.053), and the viremic episodes longer
      (P=0.015), as compared to asymptomatically HCMV-infected patients. The
      serological pre-transplant status was the major risk factor for the development
      of HCMV disease, showing highest risk for seropositive patients receiving a
      seronegative graft, whereas donor type (related or unrelated) and graft type
      (bone marrow or peripheral blood mobilized stem cells) did not have an influence.
      HCMV infection proved to be a risk factor for the development of non-viral
      opportunistic infections (P=0.002).

PMID- 16788684
TI  - Apoptotic lymphocytes and CD34+ cells in cryopreserved cord blood detected by the
      fluorescent vital dye SYTO 16 and correlation with loss of L-selectin (CD62L)
      expression.
AB  - Discrimination between live and apoptotic cells is important for accurate
      determination of viable CD34(+) cells in hematopoietic stem cell transplant
      products. SYTO16 is a sensitive fluorescent dye for discriminating live from
      apoptotic leukocytes. The incidence of apoptotic leukocytes in paired samples of
      fresh and cryopreserved-thawed cord blood (CB) was determined by the SYTO16/7-AAD
      flow cytometric assay. Cell migration and expression of the cell homing molecule
      L-selectin (CD62L) was determined in relation to SYTO16 staining. SYTO16 detected
      significant proportions of apoptotic lymphocytes and CD34(+) cells in fresh and
      thawed CB buffy-coat samples that were not detected by 7-AAD. Compared to fresh
      CB, the proportion of apoptotic lymphocytes and CD34(+) cells significantly
      increased following thawing. Significantly higher proportions of live
      SYTO16(bright) lymphocytes and CD34(+) cells were found in the migrated cell
      population compared to the non-migrated population. Significantly fewer
      lymphocytes and CD34(+) cells expressed CD62L following thawing. Absence of CD62L
      expression was strongly correlated with apoptotic/SYTO16(dim) lymphocytes and
      CD34(+) cells. Cryopreserved-thawed CB contains significant proportions of
      apoptotic lymphocytes and CD34(+) cells that are not detected by 7-AAD. SYTO16
      offers a sensitive method for discrimination of live from apoptotic leukocytes
      and assists in accurate assessment of CB quality and suitability for use in
      clinical transplantation.

PMID- 16788687
TI  - Cardiovascular events following renal transplantation: role of traditional and
      transplant-specific risk factors.
AB  - Cardiovascular mortality is increased in transplant recipients. However, studies
      including non-fatal events are critical to assess the burden of disease and to
      identify novel risk factors. We described the incidence of fatal and non-fatal
      events, and explored associations and interactions among traditional and
      transplant-specific risk factors and cardiovascular events (CVE) in a cohort of
      922 patients transplanted between 1993 and 1998. One hundred and seventy-six
      patients experienced 201 CVE (111 cardiac, 48 cerebrovascular, 42 peripheral
      vascular). Most CVE were non-fatal. Factors associated with cardiac events were
      (adjusted hazard ratios) tobacco (3.53; P<0.001), obesity (2.92; P<0.001),
      diabetes (2.63; P<0.001), multiple rejections (2.19; P=0.008), prior CVE (2.0;
      P=0.004), dialysis >1 year (1.91; P=0.007), and overweight status (1.68; P=0.04);
      with cerebrovascular events: diabetes and peritoneal dialysis (11.95; P<0.001),
      age >45 (6.77; P<0.001), diabetes (4.87; P<0.001), prior CVE (3.73; P<0.001),
      creatinine >141 micromol/l (3.16; P=0.001), peritoneal dialysis (3.06; P=0.027),
      and obesity (0.32; P=0.046); with peripheral-vascular events: diabetes (8.48;
      P<0.001), tobacco and cytomegalovirus (3.88; P<0.001), age >45 (2.31; P=0.019),
      and prior CVE (2.25; P=0.016); with mortality: tobacco and deceased-donor (3.52;
      P<0.001), age >45 (1.81; P=0.002), diabetes (1.76; P=0.002), pulse pressure
      (1.64; P=0.029), prior CVE (1.52; P=0.04), and dialysis >1 year (1.47; P=0.04).
      The majority of CVE post-transplant were non-fatal. Previous CVE was strongly
      associated with CVE post-transplant. Interactions among transplant-specific and
      traditional risks impacted significantly the incidence of CVE. Modifiable factors
      such as duration of dialysis, deceased-donor transplantation, and acute rejection
      should be viewed as cardiovascular risks.

PMID- 16788688
TI  - Adenosine is upregulated during peritonitis and is involved in downregulation of
      inflammation.
AB  - Loss of function of the peritoneal membrane is associated with peritonitis.
      Adenosine levels in sites of inflammation were shown to increase and exhibit
      immunoregulatory effects. Our aim was to elucidate the regulatory role of
      adenosine during peritonitis and to test the involvement of peritoneal
      mesothelial cells (PMC) in adenosine regulation. In a mice model of Escherichia
      coli peritonitis, the adenosine A(2A) receptor (A(2A)R) agonist (CGS21680)
      prevented leukocyte recruitment and reduced tumor necrosis factor alpha (TNF
      alpha) and interleukin-6 (IL-6) levels. Peritonitis induced the elevation of
      adenosine with a peak at 24 h. Analysis of adenosine receptor levels on
      peritoneum showed that A(1) receptor (A(1)R) protein levels peak at 12 h after
      inoculation and then return to baseline at 24 h, whereas high affinity A(2A)R
      protein levels peak at 24 h concomitantly with the peak of adenosine
      concentration. Low affinity A(2B) receptor (A(2B)R) levels elevated slowly,
      remaining elevated up to 48 h. In human PMC (HPMC), the early cytokines, IL-1
      alpha, and TNF-alpha upregulated the A(2B) and A(2A) receptors. However,
      interferon-gamma (IFN-gamma) upregulated the A(2B)R and decreased A(2A)R levels.
      Treatment with the A(2A)R agonist reduced IL-1-dependent IL-6 secretion from
      HPMC. In conclusion, the kinetics of adenosine receptors suggest that at early
      stage of peritonitis, the A(1)R dominates, and later its dominance is replaced by
      the G stimulatory (Gs) protein-coupled A(2A)R that suppresses inflammation. Early
      proinflammatory cytokines are an inducer of the A(2A)R and this receptor reduces
      their production and leukocyte recruitment. Future treatment with adenosine
      agonists should be considered for attenuating the damage to mesothelium during
      the course of acute peritonitis.

PMID- 16788689
TI  - Prevalence of complications in children with chronic kidney disease according to
      KDOQI.
AB  - The Kidney Disease Outcome and Quality Initiative (KDOQI) Group recommended
      guidelines for the monitoring and treatment of chronic kidney disease (CKD) in
      2002. These recommendations were based on the prevalence of known complications
      as seen in adults. In children, the exact prevalence of these complications is
      unknown. We therefore conducted a cross-sectional study of 366 patients with CKD
      in a single center to analyze the prevalence of these complications across all
      stages of kidney disease. Patients were categorized to their KDOQI stage of CKD
      according to their estimated renal function as determined from serum cystatin C.
      Fifty seven percent of patients had CKD stage 1, 29.0% stage 2, 10.4% stage 3 and
      4.1% stages 4+5. Uropathies (31%) were the most prevalent causes of CKD.
      Glomerular disease accounted for 27%. The overall prevalence of complications was
      as follows: hypertension 70.2%, anemia 36.6%, proteinuria 11.5%, and metabolic
      bone disease 16.9%. Metabolic bone disease and anemia occurred frequently, even
      with a glomerular filtration rate >60 ml/min/1.73 m2. Growth failure (11.5%) was
      also common and is not a component of the KDOQI guidelines for CKD in children.
      The prevalence of all complications increased with worsening stage of kidney
      disease (all P-values significant). In summary, this study supports the KDOQI
      guidelines in defining and staging CKD in children. This study also highlights
      the differences in the causes and complications that occur in CKD between adults
      and pediatrics. We recommend modification of the KDOQI guidelines for children to
      reflect the differences described in this paper.

PMID- 16788690
TI  - Association between residence location and likelihood of kidney transplantation
      in Aboriginal patients treated with dialysis in Canada.
AB  - For reasons that are not well understood, Aboriginal people with end-stage renal
      disease (ESRD) have lower rates of kidney transplantation. We hypothesized that
      distance between residence location and the closest transplant center was greater
      in Aboriginal dialysis patients and would partially explain the lower rate of
      transplantation in this population. We studied a random sample of 9905 patients
      initiating dialysis in Canada between 1990 and 2000. We calculated the distance
      between residence location at dialysis inception and the closest transplant
      center. Cox proportional hazards models were used to examine the relation between
      residence location and the likelihood of transplantation over a median period of
      2.3 years. The proportion of Aboriginal participants living <or=50, 50.1-150,
      150.1-300, and >300 km from the closest transplant center was 25, 18, 18, and 39%
      respectively, compared with 55, 19, 11, and 15% among white subjects. The
      relative likelihood of transplantation was significantly lower for Aboriginal
      compared to white participants across all four distance strata, with no apparent
      effect of residence location. For example, the relative likelihood of
      transplantation was hazard ratio (HR) 0.47, 95% confidence interval (CI) (0.31
      0.72) in Aboriginal participants residing <or=50 and 0.55 (0.38-0.80) in those
      residing >300 km from the closest transplant center. Results were similar for
      transplants from deceased donors and living donors, and in all seven regions
      studied. In conclusion, remote location of residence does not explain the lower
      rate of kidney transplantation among Aboriginal people treated for ESRD in
      Canada.

PMID- 16788691
TI  - Inter-method variability in PTH measurement: implication for the care of CKD
      patients.
AB  - The National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative
      guidelines recommend to maintain the serum intact parathyroid hormone (PTH)
      concentration between 150 and 300 ng/l in chronic kidney disease (CKD) stage 5
      patients. As these limits were derived from studies that used the Allegro intact
      PTH assay, we aimed to evaluate whether they were applicable to other PTH assays.
      We compared the PTH concentrations measured with 15 commercial immunoassays in 47
      serum pools from dialysis patients, using the Allegro intact PTH assay as the
      reference. We also evaluated the recovery of graded amounts of synthetic 1-84 and
      7-84 PTH added separately to a serum pool. Although the assays were highly
      correlated, the concentrations differed from one assay to another. The median
      bias between the tested assays and the Allegro intact PTH assay ranged from -44.9
      to 123.0%. When the PTH concentrations were 150 or 300 ng/l with the Allegro
      intact PTH assay, they ranged with other assays from 83 to 323 ng/l and from 160
      to 638 ng/l, respectively. The tested assays recognized 7-84 PTH with various
      cross-reactivities, whereas a given amount of 1-84 PTH was recovered differently
      by these assays. We found important inter-method variability in PTH results owing
      to both antibody specificity and standardization reasons. The unacceptable
      consequence is that opposite therapeutic attitudes may be reached in a single
      patient depending on the PTH assay used. We propose to use assay-specific
      decision limits for CKD patients, or to apply a correcting factor to the PTH
      results obtained with a given assay.

PMID- 16788692
TI  - STAT3 attenuates EGFR-mediated ERK activation and cell survival during oxidant
      stress in mouse proximal tubular cells.
AB  - We have shown that renal epithelial cell survival depends on the sustained
      activation of the extracellular signal-regulated protein kinase (ERK) and lack of
      this activation was associated with death during oxidative stress. ERK is
      activated via the canonical epidermal growth factor receptor (EGFR)-Ras-MEK
      pathway, which could be attenuated by oxidants. We now show that the failure to
      activate ERK in a sustained manner during severe oxidative stress is owing to the
      activation of the signal transducer and activator of transcription-3 (STAT3)
      rather than the failure to activate the EGFR. Tyrosine phosphorylation of the
      EGFR and STAT3 was studied in hydrogen peroxide (H(2)O(2))-treated mouse proximal
      tubule (TKPTS) cells or in mouse kidney after ischemia/reperfusion (I/R) injury
      by Western blotting. STAT3 activation was inhibited by either pharmacologically
      (AG490) through its upstream janus kinase (JAK2) or by a dominant-negative STAT3
      adenovirus. EGFR was inhibited by AG1478. Survival was determined by fluorescence
      activated cell sorter analysis and trypan blue exclusion. We found that the EGFR
      was phosphorylated on its major autophosphorylation site (Tyr1173) regardless of
      the H(2)O(2) dose. On the other hand, both I/R and severe oxidative stress - but
      not moderate stress - increased tyrosine phosphorylation of STAT3 in an EGFR and
      JAK2-dependent manner. Inhibition of JAK2 or STAT3 lead to increased ERK
      activation and survival of TKPTS cells during severe oxidative stress. Our data
      suggest a role of tyrosine-phosphorylated STAT3 in the suppression of ERK
      activation. These data suggest that the STAT3 pathway might represent a new
      target for improved survival of proximal tubule cells exposed to severe oxidant
      injury.

PMID- 16788693
TI  - Glomerular hyperfiltration predicts the development of microalbuminuria in stage
      1 hypertension: the HARVEST.
AB  - Factors related to the development of microalbuminuria in hypertension are not
      well known. We did a prospective study to investigate whether glomerular
      hyperfiltration precedes the development of microalbuminuria in hypertension. We
      assessed 502 never-treated subjects screened for stage 1 hypertension without
      microalbuminuria at baseline and followed up for 7.8 years. Creatinine clearance
      was measured at entry. Urinary albumin and ambulatory blood pressure were
      measured at entry and during the follow-up until subjects developed sustained
      hypertension needing antihypertensive treatment. Subjects with hyperfiltration
      (creatinine clearance >150 ml/min/1.73 m2, top quintile of the distribution) were
      younger and heavier than the rest of the group and had a greater follow-up
      increase in urinary albumin than subjects with normal filtration (P<0.001). In
      multivariable linear regression, creatinine clearance adjusted for confounders
      was a strong independent predictor of final urinary albumin (P<0.001). In
      multivariable Cox regression, patients with hyperfiltration had an adjusted
      hazard ratio for the development of microalbuminuria based on at least one
      positive measurement of 4.0 (95% confidence interval (CI), 2.1-7.4, P<0.001) and
      an adjusted hazard ratio for the development of microalbuminuria based on two
      consecutive positive measurements of 4.4 (95% CI, 2.1-9.2, P<0.001), as compared
      with patients with normal filtration. Age, female gender, and 24 h systolic blood
      pressure were other significant predictors of microalbuminuria. In conclusion,
      stage 1 hypertensive subjects with glomerular hyperfiltration are at increased
      risk of developing microalbuminuria. Early intervention with medical therapy may
      be beneficial in these subjects even if their blood pressure falls below normal
      limits during follow-up.

PMID- 16788694
TI  - Effect of mycophenolate mofetil on rat kidney grafts with prolonged cold
      preservation.
AB  - The impact of mycophenolate mofetil (MMF) on initial renal transplant function is
      not well characterized. We tested how MMF may modulate graft function and
      survival in a syngeneic rat kidney transplantation model after prolonged cold
      preservation. Donor kidneys were preserved in University of Wisconsin for either
      24 or 39 h prior to transplantation into nephrectomized rats. Recipients received
      MMF (20 mg/kg/day) or vehicle. Mycophenolic acid (MPA) blood concentrations were
      measured by high-performance liquid chromatography. The inflammatory response,
      tubular epithelial proliferation, and histologic damage 3 days post
      transplantation were assessed microscopically. In the 24 h cold storage (c.s.)
      group serum-creatinine was measured. In the 39 h c.s. group 1-week recipient
      survival was determined. After 24 h of c.s., recipient survival was 100%. The
      number of T-cell infiltrates was low and not influenced by MMF, whereas renal
      ED1+ cell infiltration was significantly suppressed by MMF. Tubular cell
      proliferation was enhanced by MMF. Serum-creatinine levels and renal histology
      were comparable between MMF and vehicle-treated animals. In the 39 h c.s. group,
      recipient survival was 20% in MMF-treated vs 90% in vehicle-treated animals
      (P=0.001). MMF effectively suppressed inflammatory cell infiltration and
      inhibited tubular cell proliferation. MMF-induced structural damage was most
      striking in the renal papilla. In rat kidney grafts with moderate preservation
      injury (24 h c.s.), MMF, given at an immunosuppressive dose, showed predominantly
      antiinflammatory effects without compromising graft function. In grafts with
      severe preservation injury (39 h c.s.), MMF caused irreversible structural damage
      and inhibited tubular cell regeneration resulting in renal failure.

PMID- 16788696
TI  - Subclinical rejection impairs glomerular adaptation after renal transplantation.
AB  - After transplantation, glomerular volumes increases and large glomerular volume
      at 4 months is associated with better renal function. The aim is to characterize
      glomerular adaptation after the fourth month in two serial protocol biopsies and
      its relationship with subclinical rejection and chronic allograft nephropathy
      (CAN). Mean glomerular volume (Vg) was estimated according to the Weibel and
      Gomez method in a 4-month and 1-year serial protocol biopsies in 61 stable
      grafts. Glomerular enlargement (deltaVg) was calculated as the Vg difference
      between both biopsies. Banff schema was used to evaluate renal biopsies. Vg
      increased from 4.4+/-2.4 to 5.7+/-2.6 x 10(6) microm3 (P<0.001). Mean deltaVg was
      1.0 x 10(6) microm3. Patients with deltaVg<1 were considered as patients with
      impaired glomerular enlargement (n=29). Impaired glomerular enlargement was
      associated with increased acute index score in the 4-month (1.83+/-1.56 vs 1.06+/
      1.48; P<0.05) and 1-year protocol biopsies (1.52+/-1.59 vs 0.62+/-1.07; P<0.05).
      Impaired glomerular enlargement was also associated with increased progression of
      chronic lesions between the 4-month and 1-year biopsy in the glomerular (0.17+/
      0.38 vs 0.55+/-0.63; P<0.01), tubular (0.38+/-0.56 vs 0.83+/-0.85; P<0.01), and
      interstitial compartment (0.41+/-0.57 vs 0.90+/-0.86; P<0.01). The proportion of
      sclerotic glomeruli between both biopsies increased in patients with impaired
      glomerular enlargement (1.5+/-3.9 to 5.3+/-10.1, P<0.05) while it did not modify
      in patients with glomerular enlargement (2.1+/-7.3 vs 2.6+/-4.5; P=NS). During
      the first year, glomeruli enlarge but this adaptation mechanism is impaired in
      patients with subclinical rejection. Moreover, impaired glomerular enlargement is
      associated with progression of CAN.

PMID- 16788695
TI  - 24-h ambulatory blood pressure is linked to chromosome 18q21-22 and genetic
      variation of NEDD4L associates with cross-sectional and longitudinal blood
      pressure in Swedes.
AB  - Numerous linkage studies have indicated chromosome 18q21-22 as a locus of
      importance for blood pressure regulation. This locus harbors the neural precursor
      cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is
      instrumental for the regulation of the amiloride-sensitive epithelial sodium
      channel (ENaC). In a linkage study of 16 markers (including two single nucleotide
      polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70
      104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest
      evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L
      locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we
      subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative
      splicing leads to varying expression of a functionally crucial C2 domain, was
      associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over
      time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L
      marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01),
      DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A
      quantitative transmission disequilibrium test in the family material of the
      rs4149601 supported this NEDD4L variant as being at least partially causative of
      the linkage result. In conclusion, our findings suggest that the chromosome 18
      linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross
      sectional and longitudinal blood pressure, possibly as a consequence of altered
      NEDD4L interaction with ENaC.

PMID- 16788697
TI  - Direct maxacalcitol injection into hyperplastic parathyroids improves skeletal
      changes in secondary hyperparathyroidism.
AB  - Direct maxacalcitol (OCT) injection into a parathyroid gland (PTG) ameliorates
      several important etiologic factors of resistance to medical treatments for
      secondary hyperparathyroidism (s-HPT): the upregulations of vitamin D receptor
      (VDR) and Ca-sensing receptor (CaSR) in PTGs and the regression of PTG
      hyperplasia by the induction of apoptosis. In this study, we evaluated the bone
      histomorphology on the basis of maintaining these effects in advanced s-HPT.
      Five/six nephrectomized Sprague-Dawley rats were fed a high-phosphorus and low
      calcium diet for 8 weeks. These rats were divided into four treatment groups: (1)
      basic uremic (at the baseline), (2) direct OCT single injection into PTGs (DI
      OCT) followed by OCT intravenous administration for 4 weeks (IV-OCT), (3) direct
      vehicle injection and IV-OCT, and (4) no treatment for an additional 4 weeks. The
      effects of these treatments on serum intact-parathyroid hormone (PTH) level, PTG
      weight, VDR and CaSR expression levels in PTGs, and bone histomorphometric
      parameters were investigated. In the DI-OCT+IV-OCT group, the significant
      decrease in serum intact-PTH level was maintained by the following IV-OCT. A
      significant decrease in PTG weight and the upregulations of VDR and CaSR
      expression levels in PTGs were also observed. Bone histomorphometric analysis
      showed significant improvements in osteitis fibrosa in both cancellous and
      cortical bones. However, these findings were not observed in the other groups.
      These results suggest that osteitis fibrosa caused by advanced s-HPT can be
      successfully reversed by a control of PTH at an appropriate level through the
      improvement of PTG hyperplasia as induced by DI-OCT+IV-OCT.

PMID- 16788699
TI  - Body fat mass and lean mass as predictors of survival in hemodialysis patients.
AB  - A higher body mass index (BMI) is a predictor of better survival in hemodialysis
      patients, although the relative importance of body fat and lean mass has not been
      examined in the dialysis population. We performed an observational cohort study
      in 808 patients with end-stage renal disease on maintenance hemodialysis. At
      baseline, fat mass was measured by dual-energy X-ray absorptiometry and expressed
      as fat mass index (FMI; kg/m2). Lean mass index (LMI) was defined as BMI minus
      FMI. During the mean follow-up period of 53 months, 147 deaths, including 62
      cardiovascular (CV) and 85 non-CV fatal events, were recorded. In univariate
      analysis, LMI was not significantly associated with CV or non-CV death, whereas a
      higher FMI was predictive of lower risk for non-CV death. Analyses with
      multivariate Cox models, which took other confounding variables as covariates,
      indicated the independent associations between a higher LMI and a lower risk of
      CV death, as well as between a higher FMI and a lower risk of non-CV death. These
      results indicate that increased fat mass and lean mass were both conditions
      associated with better outcomes in the dialysis population.

PMID- 16788705
TI  - Taxonomy: DNA barcodes: recent successes and future prospects.

PMID- 16788698
TI  - Noninhibitory PAI-1 enhances plasmin-mediated matrix degradation both in vitro
      and in experimental nephritis.
AB  - Plasminogen activator inhibitor-type 1 (PAI-1) is thought to be profibrotic by
      inhibiting plasmin generation, thereby decreasing turnover of pathological
      extracellular matrix (ECM). A mutant, noninhibitory PAI-1 (PAI-1R) was recently
      shown by us to increase glomerular plasmin generation and reduce disease in anti
      thy-1 nephritis. Here, in vitro and in vivo studies were performed to determine
      whether enhanced plasmin-dependent ECM degradation underlies the therapeutic
      effect of PAI-1R. 3H-labeled ECM was produced by rat mesangial cells (MCs). The
      effect of wild-type PAI-1 (wt-PAI-1) and PAI-1R on ECM degradation by newly
      plated MCs was measured by the release of 3H into medium. In vivo, anti-thy-1
      nephritis was assessed in normal, untreated diseased and PAI-1R treated rats with
      or without the plasmin/plasminogen inhibitor, tranexamic acid (TA). wt-PAI-1
      totally inhibited plasmin generation and reduced ECM degradation by 76% when
      exogenous plasminogen was added. Although PAI-1R alone had no effect, PAI-1R in
      the presence of wt-PAI-1 reversed the wt-PAI-1 inhibition of ECM degradation in a
      time- and dose-dependent manner (P<0.001). Plasmin activity and zymography were
      consistent with ECM degradation. Plasmin inhibitors: alpha2-antiplasmin,
      aprotinin, and TA completely blocked PAI-1R's ability to normalize ECM
      degradation (P<0.001). Consistent with the in vitro results, TA reversed PAI-1R
      induced reductions in glomerular fibrin and ECM accumulation. Other measures of
      disease severity were either unaltered or partially reversed. PAI-1R reduces
      pathological ECM accumulation, in large part through effectively competing with
      native PAI-1 thereby restoring plasmin generation and increasing plasmin
      dependent degradation of matrix components.

PMID- 16788706
TI  - Quantitative genetics: wholesale analysis of genes, traits and microarrays.

PMID- 16788707
TI  - Oral magnesium supplementation in asthmatic children: a double-blind randomized
      placebo-controlled trial.
AB  - OBJECTIVE: To investigate the long-term effect of oral magnesium supplementation
      on clinical symptoms, bronchial reactivity, lung function and allergen-induced
      skin responses in children and adolescents with moderate persistent asthma.
      DESIGN: A double-blind randomized parallel placebo-controlled study. SETTING AND
      SUBJECTS: The patients were recruited from the Pediatric Outpatient Clinic,
      Division of Pulmonology, Allergy and Immunology, and followed at the Center for
      Investigation in Pediatrics at State University of Campinas Hospital, Brazil.
      Thirty-seven out of 72 patients met the study criteria. There were no dropouts.
      INTERVENTION: The 37 patients (aged 7-19 years, 19 males) were randomized in two
      groups: magnesium (n=18, 300 mg/day) and placebo (n=19), during 2 months. Both
      patient groups received inhaled fluticasone (250 microg twice a day) and
      salbutamol as needed. The primary outcome was bronchial reactivity evaluated with
      methacholine challenge test (PC20). RESULTS: After a follow-up of 2 months, the
      methacholine PC20 for testing bronchial reactivity has augmented significantly in
      the magnesium group only. The skin responses to recognized antigens have also
      decreased in patients treated with magnesium. The forced vital capacity (FVC),
      the forced expiratory volume at first second (FEV1), the forced expiratory flow
      at 25-75 and the FEV1/FVC ratio were similar in both groups. The magnesium group
      presented fewer asthma exacerbations and used less salbutamol compared to the
      placebo group. CONCLUSIONS: Oral magnesium supplementation helped to reduce
      bronchial reactivity to methacholine, to diminish their allergen-induced skin
      responses and to provide better symptom control in pediatric patients with
      moderate persistent asthma treated with inhaled fluticasone.

PMID- 16788709
TI  - Fatty acid handling protein expression in adipose tissue, fatty acid composition
      of adipose tissue and serum, and markers of insulin resistance.
AB  - OBJECTIVE: Proteins involved in cellular fatty acid (FA) uptake and metabolism
      may be of relevance in the context of disturbed FA metabolism associated with
      insulin resistance. Therefore this study investigated relationships between FA
      handling protein mRNA expression in adipose tissue, FA composition of adipose
      tissue and serum, and markers of insulin resistance. SUBJECTS: 75 subjects with a
      range of insulin sensitivities recruited from a cohort of 294 healthy 63-year-old
      Swedish men. MEASUREMENTS: Anthropometric and biochemical variables (e.g. waist
      hip-ratio (WHR) and homeostasis model assessment (HOMA) index of insulin
      sensitivity), FA composition of the subcutaneous (s.c.) gluteal adipose tissue,
      serum nonesterified FA (NEFA) and serum phospholipid compartments (by gas-liquid
      chromatography; n = 294), and mRNA levels of FA handling proteins (adipocyte and
      keratinocyte lipid binding proteins, fatty acid transport protein (FATP) -1 and 
      4, CD36/fatty acid translocase, plasma membrane fatty acid binding protein, and
      acyl-CoA synthase-1 (ACS1)) in s.c. gluteal adipose tissue (by quantitative real
      time polymerase chain reaction; n = 75). RESULTS: ACS1 expression was negatively
      correlated with measures of insulin resistance and central obesity (ACS1 versus
      HOMA: r = -0.28, P<0.05; ACS1 versus WHR: r = -0.23, P<0.05), with an opposite
      trend for FATP4. Further analysis of ACS1 expression levels revealed correlations
      with adipose tissue 16:0 (r = -0.27, P<0.05) and NEFA 16:1 (r = 0.29, P<0.05), FA
      composition variables which in turn correlated with HOMA index (r = 0.39, P<0.001
      and r = -0.23, P<0.05, respectively, n = 75). Moreover, NEFA 16:1 predicted ACS1
      expression independently of HOMA, WHR and adipose tissue 16:0 in multiple
      regression analysis (standardized coefficient = 0.27, P<0.05). CONCLUSION:
      Significant associations were found between measures of insulin sensitivity,
      adipose tissue FA handling protein expression, and specific FA composition
      variables. Although causal relationships could not be identified these findings
      suggest a role of FA handling proteins in relation to insulin sensitivity, via
      their involvement in FA trafficking and metabolism. In particular they indicate
      links between ACS1 activity, the distribution of 16:0 and 16:1, and insulin
      sensitivity, which may be of physiological relevance.

PMID- 16788708
TI  - Trends of food intake in Portugal, 1987-1999: results from the National Health
      Surveys.
AB  - OBJECTIVE: To assess trends of food intake in Portugal. DESIGN: Analysis of three
      cross-sectional studies: 1987, 1995-1996 and 1998-1999. SETTING: Representative
      samples of free-living individuals. SUBJECTS: 64 734 men and 71 282 women.
      INTERVENTIONS: Food intake was assessed by questionnaires inquiring the number of
      meals and which foodstuffs (fish, meat, milk, rice/pasta/potatoes, soup,
      vegetables and fruit) had been consumed the day before. RESULTS: Age-adjusted
      average number of meals decreased from 3.3+/-0.1 in 1987 to 2.9+/-0.1 in 1998
      1999 in both genders (P<0.001). In men, the percentage of subjects consuming
      meat, milk and potatoes/rice/pasta increased from 73, 66 and 91% in 1987 to 83,
      74 and 95% in 1998-1999, respectively. The percentage of subjects consuming soup
      and fish decreased from 70 and 56% in 1987 to 62 and 53% in 1998-1999,
      respectively. In women, the percentage of subjects consuming meat, milk,
      potatoes/rice/pasta and vegetable increased from 70, 66, 89 and 71% in 1987 to
      78, 77, 93 and 83% in 1998-1999, respectively. The percentage of subjects
      consuming soup and fish decreased from 70 and 55% in 1987 to 64 and 53% in 1998
      1999, respectively. These trends were more pronounced in the younger age, which
      also displayed a higher frequency of snacking. Multivariate analysis adjusting
      for age group, region and educational level showed that the consumption of meat,
      milk and vegetables increased and the consumption of soup, fish and fruit
      decreased in 1998-1999 relative to 1995-1996. CONCLUSIONS: Within a decade, the
      Portuguese dietary pattern has changed considerably, shifting from a traditional,
      south European to a more Westernized, protein-rich diet. SPONSORSHIP: The Unidade
      de Nutricao e Metabolismo of the Instituto de Medicina Molecular is partially
      funded by a grant from the FCT (Fundacao para a Ciencia e a Tecnologia) ref. RUN
      437.

PMID- 16788710
TI  - Epidemiology of obesity and hypertension and related risk factors in Uzbekistan.
AB  - OBJECTIVE: This study examined the prevalence of obesity and hypertension and
      associated behavioral risk factors in adult men and women in Uzbekistan. The
      study also examined the association between obesity and hypertension. METHOD: The
      analysis used data from the 2002 Uzbekistan Health Examination Survey, which
      included a nationally representative sample of 2333 men aged 15-59 years and 5463
      women aged 15-49 years. The survey measured height, weight and blood pressure and
      included questions on physical activity, dietary habits, tobacco smoking, alcohol
      use and other characteristics. The analysis was conducted using binary and
      multinomial logistic regression methods, separately for men and women. RESULTS:
      Eating animal source protein and tobacco smoking in the past were positively
      associated with obesity, but there were no consistent associations with other
      dietary indicators, physical activity level or alcohol use. Obese men and women
      were about three times as likely to suffer from hypertension as those with a
      normal BMI (odds ratio (OR)=3.01; 95% confidence interval (CI): 1.67-5.44;
      P<0.001 for men and OR=2.82; 95% CI: 2.05-3.86; P<0.001 for women), independent
      of physical activity level, dietary habits, tobacco smoking and other factors.
      For men, the risk of hypertension was strongly positively associated with BMI
      only at BMI levels above 25 kg/m(2), but for women a positive relationship was
      observed at all BMI levels. CONCLUSION: The study found a strong positive
      association between obesity and hypertension in adult men and women in
      Uzbekistan. The shape of the relationship between BMI and hypertension is
      different for women than for men, requiring further research to explore this
      relationship.

PMID- 16788711
TI  - Effects of exercise and training in hypoxia on antioxidant/pro-oxidant balance.
AB  - OBJECTIVE: The aim was to investigate the effects of acute exercise under hypoxic
      condition and the repetition of such exercise in a 'living low-training high'
      training on the antioxidant/prooxidant balance. DESIGN: Randomized, repeated
      measures design. SETTING: Faculte de Medecine, Clermont-Ferrand, France.
      SUBJECTS: Fourteen runners were randomly divided into two groups. A 6-week
      endurance training protocol integrated two running sessions per week at the
      second ventilatory threshold into the usual training. INTERVENTION: A 6-week
      endurance training protocol integrated two running sessions per week at the
      second ventilatory threshold into the usual training. The first hypoxic group
      (HG, n=8) carried out these sessions under hypoxia (3000 m simulated altitude)
      and the second normoxic group (NG, n=6) in normoxia. In control period, the
      runners were submitted to two incremental cycling tests performed in normoxia and
      under hypoxia (simulated altitude of 3000 m). Plasma levels of advanced oxidation
      protein products (AOPP), malondialdehydes (MDA) and lipid oxidizability, ferric
      reducing antioxidant power (FRAP), lipid-soluble antioxidants (alpha-tocopherol
      and beta-carotene) normalized for triacyglycerols and cholesterol were measured
      before and after the two incremental tests and at rest before and after training.
      RESULTS: No significant changes of MDA and AOPP level were observed after
      normoxic exercise, whereas hypoxic exercise induced a 56% rise of MDA and a 44%
      rise of AOPP. Plasma level of MDA and arterial oxygen hemoglobin desaturations
      after the acute both exercises were highly correlated (r=0.73). alpha-Tocopherol
      normalized for cholesterol and triacyglycerols increased only after hypoxic
      exercise (10-12%, P<0.01). After training, FRAP resting values (-21%, P<0.05) and
      alpha-tocopherol/triacyglycerols ratio (-24%, P<0.05) were diminished for HG,
      whereas NG values remained unchanged. CONCLUSIONS: Intense exercise and hypoxia
      exposure may have a cumulative effect on oxidative stress. As a consequence, the
      repetition of such exercise characterizing the 'living low-training high' model
      has weakened the antioxidant capacities of the athletes. SPONSORSHIP:
      International Olympic Committee and the Direction Regionale de la Jeunesse et des
      Sports de la Region Auvergne.

PMID- 16788712
TI  - Maternal lean body mass may be the major determinant of birth weight: A study
      from India.
AB  - This study explored the relationship of maternal body composition parameters to
      the birth weight of the offspring. Maternal anthropometric parameters (weight,
      height) and body composition by dual energy X-ray absorptiometry were measured in
      76 women from low-income group during 12-21 days postpartum. The mean+/-s.d.
      height, weight of the mothers and birth weight of the newborns were 151.5+/-5.29
      cm, 46.7+/-6.04 and 2.84+/-0.358 kg, respectively. When the relationship of
      maternal anthropometric and body composition parameters to the infants' birth
      weight was studied, maternal lean body mass was found to be the most important
      determinant of birth weight (R2 (%) = 21.3) (P < 0.001). This study highlights
      the importance of increasing lean body mass in young women for better pregnancy
      outcome.

PMID- 16788713
TI  - Positron emission tomography displacement sensitivity: predicting binding
      potential change for positron emission tomography tracers based on their kinetic
      characteristics.
AB  - There is great interest in positron emission tomography (PET) as a noninvasive
      assay of fluctuations in synaptic neurotransmitter levels, but questions remain
      regarding the optimal choice of tracer for such a task. A mathematical method is
      proposed for predicting the utility of any PET tracer as a detector of changes in
      the concentration of an endogenous competitor via displacement of the tracer
      (a.k.a., its 'vulnerability' to competition). The method is based on earlier
      theoretical work by Endres and Carson and by the authors. A tracer-specific
      predictor, the PET Displacement Sensitivity (PDS), is calculated from
      compartmental model simulations of the uptake and retention of dopaminergic
      radiotracers in the presence of transient elevations of dopamine (DA). The PDS
      predicts the change in binding potential (DeltaBP) for a given change in receptor
      occupancy because of binding by the endogenous competitor. Simulations were
      performed using estimates of tracer kinetic parameters derived from the
      literature. For D(2)/D(3) tracers, the calculated PDS indices suggest a rank
      order for sensitivity to displacement by DA as follows: raclopride (highest
      sensitivity), followed by fallypride, FESP, FLB, NMSP, and epidepride (lowest).
      Although the PDS takes into account the affinity constant for the tracer at the
      binding site, its predictive value cannot be matched by either a single
      equilibrium constant, or by any one rate constant of the model. Values for
      DeltaBP have been derived from published studies that employed comparable
      displacement paradigms with amphetamine and a D(2)/D(3) tracer. The values are in
      good agreement with the PDS-predicted rank order of sensitivity to displacement.

PMID- 16788714
TI  - Characteristic features of in vivo skin microvascular reactivity in CADASIL.
AB  - CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy) is caused by mutations in the Notch3 receptor expressed at
      the surface of vascular smooth muscle cells. The functional consequences of the
      disease at the peripheral microcirculation level are incompletely elucidated. In
      this study, we aimed to assess, in vivo, the endothelium-dependent and
      independent vasodilation of the skin microvasculature in CADASIL patients. Twenty
      three affected subjects were compared with 23 gender and age-matched controls.
      The brachial artery endothelium-dependent and endothelium-independent
      vasodilation were assessed after forearm cuff occlusion and nitroglycerin
      administration. Skin vasoreactivity to transcutaneous administration of
      acetylcholine and sodium nitroprussiate, and after postocclusive hyperemia were
      measured by Laser Doppler flowmetry. The maximum changes in the diameter of the
      brachial artery after the cuff release or after nitroglycerin administration did
      not differ between patients and controls. With iontopheresis, only the peak value
      of the dose response was found decreased in normocholesterolemic patients after
      nitroprussiate administration. The postocclusive test revealed a large increase
      of the time to peak value and whole duration of the hyperemic response in CADASIL
      patients. The results of this study show that the skin vasoreactivity is altered
      in CADASIL. Particularly, the kinetics of reactive hyperemia after cuff occlusion
      is dramatically changed with a lengthened and delayed response. This
      characteristic pattern may be related to the specific ultrastructural
      modifications related to Notch3 gene mutations involving smooth muscle cells in
      the microvasculature.

PMID- 16788715
TI  - Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.
AB  - We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9)
      mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9
      co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model
      where blood was injected into striatum, MMP-9 was colocalized with astrocytes
      surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as
      brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT
      blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and
      KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT
      hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous
      water content was elevated when WT blood was injected into WT brain. However,
      edema was ameliorated when MMP-9 was absent in either blood or brain or both. To
      further assess the mechanisms involved in astrocytic induction of MMP-9, we next
      examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly
      upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9
      was reduced by the free radical scavenger U83836E. Taken together, these data
      suggest that although there are large amounts of MMP-9 in blood, hemoglobin
      induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal
      sources of matrix degradation may also be an important factor in the pathogenesis
      of hemorrhagic brain edema.

PMID- 16788716
TI  - Isoflurane strongly affects the diffusion of intracellular metabolites, as shown
      by 1H nuclear magnetic resonance spectroscopy of the monkey brain.
AB  - Isoflurane is a volatile anesthetic commonly used for animal studies. In
      particular, diffusion nuclear magnetic resonance (NMR) spectroscopy is frequently
      performed under isoflurane anesthesia. However, isoflurane is known to affect the
      phase transition of lipid bilayer, possibly resulting in increased permeability
      to metabolites. Resulting decreased restriction may affect metabolite apparent
      diffusion coefficient (ADC). In the present work, the effect of isoflurane dose
      on metabolite ADC is evaluated using diffusion tensor spectroscopy in the monkey
      brain. For the five detected intracellular metabolites, the ADC exhibits a
      significant increase when isoflurane dose varies from 1% to 2%: 13%+/-8% for myo
      inositol, 14%+/-13% for total N-acetyl-aspartate, 20%+/-18% for glutamate, 27%+/
      7% for total creatine and 53%+/-17% for total choline. Detailed analysis of ADC
      changes experienced by the five different metabolites argues in favor of
      facilitated metabolite exchange between subcellular structures at high isoflurane
      dose. This work strongly supports the idea of metabolite diffusion in vivo being
      significantly restricted in subcellular structures at long diffusion time, and
      provides new insights for interpreting ADC values as measured by diffusion NMR
      spectroscopy.

PMID- 16788717
TI  - A spontaneous albino mutant of Ceratocystis resinifera results from a point
      mutation in the polyketide synthase gene, PKS1.
AB  - We characterized a spontaneous albino mutant of Ceratocystis resinifera. Compared
      with the wild-type progenitor strain, the albino mutant had a reduced linear
      growth on culture medium, but its growth on lodgepole pine sapwood was
      unaffected. The albino mutant did not produce any coloured pigment on agar media
      or wood. However, upon exposure to exogenous scytalone, an intermediate
      metabolite of the melanin pathway, the production of a brownish melanin was
      restored. This suggests that the albino phenotype resulted from a mutation
      affecting the melanin synthesis pathway, upstream of the scytalone synthesis
      step. Melanin production was restored in the mutant by transforming it with a
      wild-type copy of the Ceratocystis resinifera polyketide synthase gene, PKS1. The
      complemented transformants produced melanin, indicating that the PKS1 gene was
      defective in the albino mutant. Sequence analysis revealed that the PKS1 allele
      found in the albino contained a single point mutation that resulted in an amino
      acid change from serine to proline at the 3' end of the beta-ketoacyl synthase
      motif.

PMID- 16788718
TI  - Necrotrophic mycoparasitism of Botrytis cinerea by cellulolytic and
      ligninocellulolytic Basidiomycetes.
AB  - Twenty-six isolates representing 17 species of aphyllophoraceous, wood-decaying
      Basidiomycetes and five species of agaricoid, turf-borne, thatch-decaying
      Basidiomycetes were screened for their abilities to degrade cellulose, lignin,
      and melanin by using colorimetric degradation assays on agar media. Selected
      ligninocellulolytic Basidiomycetes capable of degrading melanin were screened for
      antagonism of Botrytis cinerea Per.:Fr. The greatest inhibition of Botrytis
      colony and hyphal growth in vitro was observed in confrontations with Irpex
      lacteus (Fr.) Fr., Trametes versicolor (L.:Fr.) Pilat, and Chondrostereum
      purpureum (Pers.:Fr.) Pouzar. Hyphal interference and necrotrophic mycoparasitism
      by these ligninocellulolytic Basidiomycetes were recognized microscopically as
      coagulation and degeneration of Botrytis cytoplasm and as coiling and invasion of
      hyphae, conidiophores, and conidia, respectively. Sclerotia of B. cinerea were
      killed and parasitized in agar media, straw mulch, or moist sand infested
      separately with these three mycoparasites.

PMID- 16788719
TI  - Purification and thermodynamic characterization of glucose oxidase from a newly
      isolated strain of Aspergillus niger.
AB  - An intracellular glucose oxidase (GOD) was isolated from the mycelium extract of
      a locally isolated strain of Aspergillus niger NFCCP. The enzyme was partially
      purified to a yield of 28.43% and specific activity of 135 U mg(-1) through
      ammonium sulfate precipitation, anion-exchange chromatography, and gel
      filtration. The enzyme showed high specificity for D-glucose, with a K(m) value
      of 25 mmol L(-1). The enzyme exhibited optimum catalytic activity at pH 5.5.
      Optimum temperature for GOD-catalyzed D-glucose oxidation was 40 degrees C. The
      enzyme displayed a high thermostability having a half-life (t(1/2)) of 30 min,
      enthalpy of denaturation (H*) of 99.66 kJ mol(-1), and free energy of
      denaturation (G*) of 103.63 kJ mol(-1). These characteristics suggest that GOD
      from A. niger NFCCP can be used as an analytical reagent and in the design of
      biosensors for clinical, biochemical, and diagnostic assays.

PMID- 16788720
TI  - Effect of some environmental parameters on fermentative hydrogen production by
      Enterobacter cloacae DM11.
AB  - Fermentative hydrogen production was carried out by Enterobacter cloacae DM11,
      using glucose as the substrate. The effects of initial substrate concentration,
      initial medium pH, and temperature were investigated. Results showed that at an
      initial glucose concentration of 1.0% (m/v), the molar yield of hydrogen was 3.31
      mol (mol glucose)(-1). However, at higher initial glucose concentration, both the
      rate and cumulative volume of hydrogen production decreased. The pH of 6.5 +/-
      0.2 at a temperature of 37 degrees C was found most suitable with respect to
      maximum rate of production of hydrogen in batch fermentation. Activation
      enthalpies of fermentation and that of thermal deactivation of the present
      process were estimated following a modified Arrhenius equation. The values were
      47.34 and 118.67 kJ mol(-1) K(-1), respectively. The effect of the addition of
      Fe(2+) on hydrogen production was also studied. It revealed that the presence of
      iron (Fe(2+)) in the media up to a concentration of 20 mg L(-1) had a marginal
      enhancing effect on total hydrogen production. A simple model developed from the
      modified Gompertz equation was applied to estimate the hydrogen production
      potential, production rate, and lag-phase time in a batch process, based on the
      cumulative hydrogen production curves, using the software program Curve Expert
      1.3.

PMID- 16788721
TI  - Bacteriocin-like substance inhibits potato soft rot caused by Erwinia carotovora.
AB  - Soft rot is a major problem encountered in potatoes during postharvest storage.
      The soft rot bacterium Erwinia carotovora was inhibited by a novel bacteriocin
      like substance (BLS) produced by Bacillus licheniformis P40. The BLS caused a
      bactericidal effect on E. carotovora cells at 30 microg mL(-1). Transmission
      electron microscopy showed that BLS-treated cells presented wrinkled bacterial
      surfaces and shrinkage of the whole cell, indicating plasmolysis. Erwinia
      carotovora cells treated with BLS were analyzed by FTIR showing differences in
      the 1390 cm(-1) and 1250-1220 cm(-1) bands, corresponding to assignments of
      membrane lipids. BLS was effective in preventing E. carotovora spoilage on potato
      tubers, reducing the symptoms of soft rot at 240 microg mL(-1) and higher
      concentrations. Soft rot development was completely blocked at 3.7 mg mL(-1).
      This BLS showed potential to protect potato tubers during storage.

PMID- 16788722
TI  - Influence of dissolved organic matter and inorganic nutrients on the biofilm
      bacterial community on artificial substrates in a northeastern Ohio, USA, stream.
AB  - Stream bacteria may be influenced by the composition and availability of
      dissolved organic matter (DOM) and inorganic nutrients, but knowledge about how
      individual phylogenetic groups in biofilm are affected is still limited. In this
      study, the influence of DOM and inorganic nutrients on stream biofilm bacteria
      was examined. Biofilms were developed on artificial substrates (unglazed ceramic
      tiles) for 21 days in a northeastern Ohio (USA) stream for five consecutive
      seasons. Then, the developed biofilm assemblages were exposed, in the laboratory,
      to DOM (glucose, leaf leachate, and algal exudates) and inorganic nutrients
      (nitrate, phosphate, and nitrate and phosphate in combination) amendments for 6
      days. Bacterial numbers in the biofilms were generally higher in response to the
      DOM treatments than to the inorganic nutrient treatments. There were also
      apparent seasonal variations in the response patterns of the individual bacterial
      taxa to the nutrient treatments; an indication that limiting resources to
      bacteria in stream biofilms may change over time. Overall, in contrast to the
      other treatments, bacterial abundance was generally highest in response to the
      low-molecular-weight DOM (i.e., glucose) treatment. These results further suggest
      that there are interactions among the different bacterial groups in biofilms that
      are impacted by the associated nutrient dynamics among seasons in stream
      ecosystems.

PMID- 16788723
TI  - Serine proteases and metalloproteases associated with pathogenesis but not host
      specificity in the Entomophthoralean fungus Zoophthora radicans.
AB  - The protease activity of a Zoophthora radicans strain that was highly infective
      toward Pieris brassicae (cabbage butterfly) larvae was compared with that of
      isogenic strains that were adapted to Plutella xylostella (diamondback moth)
      larvae through serial passage. All strains produced three distinct serine
      proteases ranging in size from 25 to 37 kDa; however, the original strain from P.
      brassicae also produced large amounts of an approximately 46 kDa metalloprotease.
      Subsequently, a cDNA encoding a 43 kDa (mature enzyme) zinc-dependent
      metalloprotease, ZrMEP1, was isolated from the original fungal strain and most
      likely corresponds to the 46 kDa protease observed with in-gel assays. ZrMEP1
      possessed characteristics of both the fungalysin and thermolysin metalloprotease
      families found in some pulmonary and dermal pathogens. This is the first report
      of this type of metalloprotease from an entomo pathogenic fungus. A cDNA encoding
      a trypsin-like serine protease, ZrSP1, was also identified and was most similar
      to a serine protease from the plant pathogen Verticillium dahliae. In artificial
      media, ZrMEP1 and ZrSP1 were found to be differentially responsive to gelatin and
      catabolite repression in the fungal strains adapted to P. brassicae and P.
      xylostella, but their expression patterns within infected larvae were the same.
      It appears that while these proteases likely play a role in the infection
      process, they may not be major host specificity determinants.

PMID- 16788724
TI  - Lateral gene transfer in Mycobacterium avium subspecies paratuberculosis.
AB  - Lateral gene transfer is an integral part of genome evolution in most bacteria.
      Bacteria can readily change the contents of their genomes to increase
      adaptability to ever-changing surroundings and to generate evolutionary novelty.
      Here, we report instances of lateral gene transfer in Mycobacterium avium subsp.
      paratuberculosis, a pathogenic bacteria that causes Johne's disease in cattle. A
      set of 275 genes are identified that are likely to have been recently acquired by
      lateral gene transfer. The analysis indicated that 53 of the 275 genes were
      acquired after the divergence of M. avium subsp. paratuberculosis from M. avium
      subsp. avium, whereas the remaining 222 genes were possibly acquired by a common
      ancestor of M. avium subsp. paratuberculosis and M. avium subsp. avium after its
      divergence from the ancestor of M. tuberculosis complex. Many of the acquired
      genes were from proteobacteria or soil dwelling actinobacteria. Prominent among
      the predicted laterally transferred genes is the gene rsbR, a possible regulator
      of sigma factor, and the genes designated MAP3614 and MAP3757, which are similar
      to genes in eukaryotes. The results of this study suggest that like most other
      bacteria, lateral gene transfers seem to be a common feature in M. avium subsp.
      paratuberculosis and that the proteobacteria contribute most of these genetic
      exchanges.

PMID- 16788726
TI  - Optimizing the medium components in bioemulsifiers production by Candida
      lipolytica with response surface method.
AB  - A response surface methodology was used to study bioemulsifier production by
      Candida lipolytica. A 2(4) full experimental design was previously carried out to
      investigate the effects and interactions of the concentrations of corn oil, urea,
      ammonium sulfate, and potassium dihydrogen orthophosphate on the emulsification
      activity (EA) of the bioemulsifier produced by C. lipolytica. The best EA value
      (3.727 units of emulsification activity (UEA)) was obtained with a medium
      composed of 0.4 g of urea, 1.1 g of ammonium sulfate, 2.04 g of potassium
      dihydrogen orthophosphate, 5 mL of corn oil, 50 mL of distilled water, and 50 mL
      of seawater. A curvature check was performed and revealed a lack of fit of the
      linear approximation. The proximity of the optimum point was evident, as was the
      need for quadratic model and second-order designs that incorporate the effect of
      the curvature. Medium constituents were then optimized for the EA using a three
      factor central composite design and response surface methodology. The second
      order model showed statistical significance and predictive ability. It was found
      that the maximum EA produced was 4.415 UEA, and the optimum levels of urea,
      ammonium sulfate, and potassium dihydrogen orthophosphate were, respectively,
      0.544% (m/v), 2.131% (m/v), and 2.628% (m/v).

PMID- 16788725
TI  - Reidentification of cellulolytic enzyme-producing Trichoderma strains W-10 and G
      39.
AB  - Strain W-10, originally identified as Trichoderma koningii, and its supposed
      mutant G-39, published for production and gene expression of cellulase and
      xylanase, demonstrated morphological characteristics distinct from those of T.
      koningii, respectively. To clarify the identification derived from morphological
      characteristics, several methods were used, including electrophoretic
      karyotyping, internal transcribed spacer (ITS) analysis of rDNA, and polymerase
      chain reaction (PCR) fingerprinting using the universal primer L45. All the
      molecular characteristics showed that strains G-39 and W-10 were identical to T.
      reesei and T. longibrachiatum, respectively. The results strongly supported that
      T. koningii G-39 and W-10 should be reassigned as T. reesei and T.
      longibrachiatum, respectively. Strain G-39 should be considered a mutant from T.
      reesei QM9414 whose spores were contaminated with those of strain W-10 during a
      laboratory operation. According to this, we declare that T. koningii G-39 and W
      10 must be renamed as T. reesei and T. longibrachiatum, respectively.

PMID- 16788727
TI  - Detection and quantification of Legionella pneumophila in water samples using
      competitive PCR.
AB  - The presence of high levels of Legionella pneumophila in man-made aquatic systems
      correlates with the incidence of nosocomial Legionnaires' disease. This requires
      a rapid, reliable, and sensitive quantification of L. pneumophila concentrations
      in suspected water systems. In this research, a homologous competitor was
      developed and evaluated in a L. pneumophila competitive polymerase chain reaction
      (cPCR) to quantify this human pathogen in a quick, cost-effective, and reliable
      way. Accuracy of cPCR was evaluated by analyzing cooling tower and tap water
      samples spiked with known concentrations of L. pneumophila bacteria, in parallel
      with the standard culture method. Legionella pneumophila amounts detected and
      calculated from cPCR and culture correlated very well: r = 0.998, P = 0.002 for
      tap water and r = 0.990, P = 0.009 for cooling tower water. Nevertheless, for
      both kinds of water samples, mean numbers of L. pneumophila calculated from cPCR
      results were always higher than those obtained by culture. This study makes it
      clear that the rapid, sensitive, and cost-effective L. pneumophila cPCR is a
      promising alternative to the standard time-consuming culture method and expensive
      real-time PCR to enumerate L. pneumophila bacteria in environmental water
      samples.

PMID- 16788728
TI  - Cultivated Beggiatoa spp. define the phylogenetic root of morphologically
      diverse, noncultured, vacuolate sulfur bacteria.
AB  - Within the last 10 years, numerous SSU rRNA sequences have been collected from
      natural populations of conspicuous, vacuolate, colorless sulfur bacteria, which
      form a phylogenetically cohesive cluster (large-vacuolate sulfur bacteria clade)
      in the gamma-Proteobacteria. Currently, this clade is composed of four named or
      de facto genera: all known Thioploca and Thiomargarita strains, all vacuolate
      Beggiatoa strains, and several strains of vacuolate, attached filaments, which
      bear a superficial similarity to Thiothrix. Some of these vacuolate bacteria
      accumulate nitrate for respiratory purposes. This clade encompasses the largest
      known prokaryotic cells (Thiomargarita namibiensis) and several strains that are
      important in the global marine sulfur cycle. Here, we report additional sequences
      from five pure culture strains of Beggiatoa spp., including the only two cultured
      marine strains (nonvacuolate), which firmly establish the root of this vacuolate
      clade. Each of several diverse metabolic motifs, including obligate and
      facultative chemolithoautotrophy, probable mixotrophy, and seemingly strict
      organoheterotrophy, is represented in at least one of the nonvacuolate strains
      that root the vacuolate clade. Because the genus designation Beggiatoa is
      interspersed throughout the vacuolate clade along with other recognized or de
      facto genera, the need for taxonomic revision is clear.

PMID- 16788729
TI  - In vivo hydrolysis of S-adenosyl-L-methionine in Escherichia coli increases
      export of 5-methylthioribose.
AB  - Escherichia coli can not synthesize methionine from 5-methylthioribose (MTR) but
      instead exports this sulfur-containing, energy-rich molecule into the surrounding
      medium. Transforming E. coli with plasmids that direct expression of the cloned
      coliphage T3 S-adenosyl-L-methionine (SAM) hydrolase (SAMase) induces the met
      regulon by cleaving the SAM co-repressor to form 5'-methylthioadenosine, which is
      then cleaved to produce MTR. To test the effect of in vivo SAMase activity on MTR
      production and its fate, cultures were incubated in the presence of
      [35S]methionine and [methyl-3H]methionine. Cells with SAMase activity produced
      significantly enhanced levels (up to 40-fold in some trials) of extracellular MTR
      -- the only radiolabeled compound released in significant amounts -- when
      compared with controls. SAM synthetase (metK) mutants transformed with SAMase
      expression vectors did not show this increase, verifying the path through SAM as
      the sole route to MTR production. SAMase expression had little or no effect on
      intracellular MTR pools, levels of radiolabeled macromolecules, or the transfer
      of methyl groups to compounds that could be precipitated by trichloroacetic acid.
      Thus, MTR appears to be a dead-end metabolite in E. coli, begging questions about
      how this has evolved, the mechanism of MTR export for the cell, and whether the
      release of MTR is important for some other activity.

PMID- 16788730
TI  - Chemical characterization and quantification of siderophores produced by marine
      and terrestrial aspergilli.
AB  - Ten aspergilli (five each from marine and terrestrial habitats) were screened for
      siderophore production. All test isolates produced siderophores as indicated by a
      positive reaction in the FeCl(3) test, chrome azurol sulphonate assay, and chrome
      azurol sulphonate agar plate test. Further, the test isolates were compared for
      their siderophore production potential and chemical characteristics. Examination
      of the chemical nature of the siderophores revealed that all test isolates
      produced hydroxamate siderophores that were trihydroxamate hexadentates. Wide
      spread occurrence of siderophores in marine isolates indicate their functional
      role in maintaining overall productivity of coastal waters. Among all test
      aspergilli, marine Aspergillus versicolor was found to be the largest siderophore
      producer (182.5 microg/mL desferrioxamine mesylate equivalent), least siderophore
      production was recorded in a marine strain of Aspergillus niger (3.5 microg/mL
      desferrioxamine mesylate equivalent).

PMID- 16788731
TI  - LARGE SCALE PURIFICATION OF BUTYRYLCHOLINESTERASE FROM HUMAN PLASMA SUITABLE FOR
      INJECTION INTO MONKEYS; A POTENTIAL NEW THERAPEUTIC FOR PROTECTION AGAINST
      COCAINE AND NERVE AGENT TOXICITY.
AB  - Pretreatment of animals with butyrylcholinesterase (EC 3.1.1.8 BChE) provides
      complete protection from the acute effects of organophosphorus nerve agents.
      Butyrylcholinesterase has also been shown to protect from cocaine toxicity. Large
      amounts of highly purified butyrylcholinesterase are needed to test the
      effectiveness of this new therapeutic agent in monkeys. Only a minimum amount of
      endotoxin can be present in a therapeutic intended for injection into monkeys.
      Our goal was to develop a large scale purification method for human BChE from
      human plasma with precautions to minimize endotoxin content. A protocol was
      developed that processed up to 100 L of human plasma at a time. Dialysis in pH
      4.0 buffer, ion exchange chromatography at pH 4, affinity chromatography on
      procainamide-Sepharose, and HPLC ion exchange at pH 7.4 yielded highly purified
      human BChE containing a low endotoxin level of about 800 EU/ml. The purified BChE
      produced by this method had a mean residence time of 56 h in mice and 93 h in
      monkeys, and caused no toxic effects. The absence of a toxic effect in monkeys
      demonstrates that the endotoxin level of 800 EU/ml was well tolerated by monkeys.

PMID- 16788732
TI  - [Abdominal vacuum device with open abdomen].
AB  - BACKGROUND: For the treatment of peritonitis or abdominal compartment syndrome,
      an open abdomen can be required. Because of the high complication rate associated
      with this method, different technical modifications were developed that are now
      being applied. Abdominal vacuum-assisted closure is increasingly favoured. We
      analyse our experience with this device in a distinct group of patients from
      gastrointestinal cancer surgery. PATIENTS AND METHOD: From June 2003 to December
      2005, 36 patients were treated with 151 double-layer abdominal vacuum devices.
      Indications for applying this device were peritonitis (n = 22), abdominal
      compartment syndrome (n = 11), and necrotising fasciitis (n = 3). Thirty-four
      patients gave anamneses of malignoma. RESULTS: Overall, the vacuum therapy
      treatment lasted a median of 13 days (range 3-48). With it, four enteric fistulas
      (11%) and four abdominal wall bleedings (11%) occurred. In our patient group, no
      new intra-abdominal abscesses were observed. Four patients died during treatment
      with the vacuum-assisted device and four afterward because of multiple organ
      failure in acute sepsis (in-hospital mortality 22%). Twenty-six patients (72%)
      underwent direct fascial closure after a median treatment duration of 10 days.
      Six patients (17%) required synthetic mesh for fascial closure. After a median
      follow-up of 100 days, two patients developed ventral hernias and two others
      showed ossification of the scar. CONCLUSION: Compared with other methods of
      temporary abdominal closure, our experience with the vacuum-assisted device
      demonstrates its advantages concerning clinical feasibility and the relatively
      low complication rate. The high rate of direct fascial closure with an acceptable
      rate of ventral hernias following vacuum-assisted abdominal closure are further
      benefits of this technique.

PMID- 16788734
TI  - Four mutations of the spastin gene in Japanese families with spastic paraplegia.
AB  - Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous
      neurodegenerative disorders characterized by slowly progressive spasticity and
      weakness of the lower limbs. HSP is caused by failure of development or selective
      degeneration of the corticospinal tracts, which contain the longest axons in
      humans. The most common form of HSP is caused by mutations of the spastin gene
      (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the
      ATPases associated with diverse cellular activities (AAA). In this study, we
      detected four causative mutations of SPAST among 14 unrelated patients with
      spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two
      deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette
      region. Three of these four mutations were novel. Previous reports and our
      results suggest that the frequency of SPAST mutations is higher among Japanese
      patients with autosomal dominant HSP, although SPAST mutations are also observed
      in patients with sporadic spastic paraplegia.

PMID- 16788733
TI  - Life on the edge: hydrogen sulfide and the fish communities of a Mexican cave and
      surrounding waters.
AB  - Most eucaryotic organisms classified as living in an extreme habitat are
      invertebrates. Here we report of a fish living in a Mexican cave (Cueva del
      Azufre) that is rich in highly toxic H(2)S. We compared the water chemistry and
      fish communities of the cave and several nearby surface streams. Our study
      revealed high concentrations of H(2)S in the cave and its outflow (El Azufre).
      The concentrations of H(2)S reach more than 300 muM inside the cave, which are
      acutely toxic for most fishes. In both sulfidic habitats, the diversity of fishes
      was heavily reduced, and Poecilia mexicana was the dominant species indicating
      that the presence of H(2)S has an all-or-none effect, permitting only few species
      to survive in sulfidic habitats. Compared to habitats without H(2)S, P. mexicana
      from the cave and the outflow have a significantly lower body condition. Although
      there are microhabitats with varying concentrations of H(2)S within the cave, we
      could not find a higher fish density in areas with lower concentrations of H(2)S.
      We discuss that P. mexicana is one of the few extremophile vertebrates. Our study
      supports the idea that extreme habitats lead to an impoverished species
      diversity.

PMID- 16788735
TI  - Cocaine use and its rheumatic manifestations: a case report and discussion.
AB  - Cocaine use can be associated with a wide spectrum of rheumatic manifestations.
      It poses a diagnostic challenge as the patients usually withhold the information
      of cocaine use, and no serological tests are available to establish this
      diagnosis. We report a patient with vasculopathic syndrome secondary to cocaine
      use. Despite initial denial of drug abuse, skin biopsy suggested the diagnosis,
      which was subsequently confirmed by urine drug testing. Differentiating cocaine
      associated pseudovasculitis from true vasculitis is necessary, as conventional
      treatment is usually ineffective without complete abstinence from cocaine use and
      may be associated with significant morbidity as well as mortality.

PMID- 16788736
TI  - Ochronotic arthropathy: pathological evidence of acute destruction of the hip
      joint.
AB  - Alcaptonuria is a hereditary disease, also known as black hip, where there is an
      accumulation of homogentisic acid pigmentation in joint cartilages. We describe a
      74-year-old woman who showed acute destruction of her left hip joint. She
      received a total hip arthroplasty on her right side in July 2000, and was
      diagnosed with ochronosis. Her postoperative follow-up was at our institutions
      outpatient department. She first complained of increasing groin pain in July
      2005, after which she had a left total hip arthroplasty in October 2005.
      Histopathologically, samples from this patient showed "fragmentation and cleft
      formation" in the cartilage of the femoral head. In addition, the samples
      revealed a remarkable degradation of proteoglycan, which is the secondary most
      abundant constituent of extra cellular matrix. These findings suggested that
      "cleft formation", where cracks develop toward the center, caused an acute
      destructive arthropathy with morphological fragility suggestive of ochronosis.

PMID- 16788737
TI  - Conversion of major ginsenoside Rb1 to ginsenoside F2 by Caulobacter leidyia.
AB  - Ginsenoside Rb1 is the most predominant ginsenoside in Panax species (ginseng)
      and the hydrolysis of this ginsenoside produces pharmaceutically active
      compounds. Caulobacter leidyia GP45, one of the isolates having strong beta
      glucosidase-producing activity, converted ginsenoside Rb(1) to the active
      metabolites by 91%. The structures of the resultant metabolites were identified
      by NMR. Ginsenoside Rb1 had been consecutively converted to ginsenoside Rd (1),
      F2(2) and compound K (3) via the hydrolyses of 20-C beta-(1-->6)-glucoside, 3-C
      beta-(1-->2)-glucoside, and 3-C beta-glucose of ginsenoside Rb1.

PMID- 16788738
TI  - Production and purification of a bioactive substance inhibiting multiple drug
      resistant bacteria and human leukemia cells from a salt-tolerant marine
      Actinobacterium sp. isolated from the Bay of Bengal.
AB  - Four marine actinobacteria tolerant to 200 g NaCl l(-1) were screened for
      antibacterial activity against eight patient-derived multiple drug resistant
      (MDR) bacteria. The active compound (MW 300.2, predicted molecular formula
      C(20)H(28)O(2)) from an actinobacterium, was inhibitory to three Gram-positive
      and three Gram-negative MDR bacteria, seven non-clinical Gram-positive, four Gram
      negative bacteria and five fungi (MIC: 3.5-4.0 microg ml(-1)). Also, 54% of human
      leukemia (HL-60) cells were killed by the compound at 0.05 microg ml(-1).
      Bioreactor production demonstrated unusual primary metabolite kinetics. Molecular
      phylogenetic analysis showed this typical intertidal inhabitant to be a member of
      the Streptomyces genus and distinct from other salt-tolerant actinobacteria. As
      no compound was found to match the properties in several electronic databases,
      our screening strategy should increase the possibility of discovering bioactive
      molecules from rare actinobacteria.

PMID- 16788739
TI  - Microbial hydrolysis of acetylated nucleosides.
AB  - Enzymatic hydrolysis of acetylated nucleosides using microbial whole cells has
      been carried out for the first time. Unlike Candida antarctica B lipase-catalysed
      alcoholysis, none of the tested microorganisms displayed a common deacetylation
      profile. Depending on the substrate and the biocatalyst used, 5'-selective
      deprotection or mixtures of mono O-acetylated products were obtained.

PMID- 16788740
TI  - Up-regulation of the endoplasmic reticulum molecular chaperone GRP78 during
      hibernation in thirteen-lined ground squirrels.
AB  - Hibernating mammals endure conditions of low body temperature and oxidative
      stress that would be highly injurious to humans and most other mammals. Stress
      conditions frequently trigger the production of molecular chaperones; in the
      endoplasmic reticulum the glucose-regulated protein-78 (GRP78) helps to minimize
      protein misfolding under stress. The present study evaluated the GRP78 response
      in seven organs of hibernating thirteen-lined ground squirrels, Spermophilus
      tridecemlineatus. Transcript levels of grp78, assessed by RT-PCR, were
      significantly higher (3.5- to 4.1-fold) in brown adipose tissue and brain of
      hibernating squirrels compared with euthermic control animals but remained low or
      stable in all other tissues. GRP78 protein content, assessed by Western blotting,
      was also elevated in brown adipose and brain during hibernation by 1.4-1.6 fold.
      A 2490 bp cDNA sequence was retrieved that contained the full length open reading
      frame of ground squirrel grp78 and the translated protein sequence of 654 amino
      acids shared 98-99% identity with GRP78 from other mammalian sources. Selected
      specific amino acid substitutions were found in the ground squirrel sequence that
      may aid GRP78 function under the near 0 degrees C body temperatures of the
      hibernating state. Electrophoretic mobility shift and supershift assays showed
      that the activating transcription factor, ATF4, binds to the promoter region of
      the grp78 gene in ground squirrel brain and may be responsible for grp78 up
      regulation during hibernation. Changes in grp78 gene and protein expression
      appear to aid stress tolerance in two highly oxygen-dependent organs that are
      critical to whole animal survival during hibernation.

PMID- 16788742
TI  - Influence of dissolved organic matter on acute toxicity of zinc to larval fathead
      minnows (Pimephales promelas).
AB  - We conducted laboratory toxicity tests in support of the development of a biotic
      ligand model (BLM) to predict acute toxicity of zinc (Zn) to fathead minnows
      (Pimephales promelas). To test the effect of dissolved organic matter (DOM) on Zn
      toxicity, we exposed larval fathead minnows to Zn in water containing elevated
      concentrations of dissolved organic carbon (DOC) in 96-h static-renewal toxicity
      tests. We tested DOM isolated from four surface waters: Cypress Swamp, Delaware;
      Edisto River, South Carolina; Suwannee River, Georgia; and Wilmington, Delaware,
      wastewater treatment effluent. The DOM isolates from the Edisto River and
      Wilmington wastewater treatment effluent contained elevated concentrations of
      NaCl (20-110x control NaCl) due to the use of a Na+-exchange resin to remove Ca2+
      and Mg2+ during the DOM isolation process. Therefore, we also performed Zn
      toxicity tests in which we added up to 20 mM NaCl to exposure solutions
      containing Cypress Swamp and Suwannee River DOM. A threshold concentration of 11
      mg DOC/L was needed to decrease Zn toxicity, after which the 96 h Zn LC50 was
      positively correlated with DOC concentration. Elevated NaCl concentrations did
      not alter Zn toxicity in the presence of DOM. In conjunction with data from other
      studies with fish and invertebrates, results of this study were used to calibrate
      Version 2.1.1 of the Zn BLM. BLM-predicted LC50s for our exposure waters
      containing elevated DOM concentrations were within the range of acceptable
      deviation relative to the observed LC50s (i.e., 0.5-2x observed LC50s); however,
      BLM-predicted LC50s for our exposure waters containing < 1 mg DOC/L were 2-3x
      lower than the observed LC50s (i.e., the BLM over-predicted the toxicity).
      Therefore, the current composite-species BLM for Zn could be improved for fathead
      minnows if that species were modeled separately from the other species used to
      calibrate Version 2.1.1.

PMID- 16788743
TI  - Ecotoxicity of sediments contaminated by the oil spill associated with the tanker
      "Prestige" using juveniles of the fish Sparus aurata.
AB  - In November 2002, the oil spill from the tanker Prestige in the Galician Coast
      caused an ecological catastrophe in Spain. The adverse effects associated with
      the contaminants bound to sediments were tested using juveniles of the fish
      Sparus aurata (seabream). The approach evaluates sediment quality by using an
      integrated assessment including chemical and ecotoxicological data. Sediment
      samples were physicochemically characterized, and the concentration of
      contaminants (polycyclic aromatic hydrocarbons-(PAHs) and metals) was measured.
      Different biomarkers of exposure (metallothioneins and ethoxyresorufin O
      deethylase activity (EROD)) and biomarkers of effect (histopathology) were
      analyzed along the time. A multivariate analysis approach was used to correlate
      concentration of contaminants and sublethal effects measured in individuals of
      fish. Results show that increasing concentrations of PAHs in sediments were
      related to increased EROD activities and histopathological lesions. This is the
      first evidence showing adverse effects associated with petroleum contamination of
      PAHs in sediments after this spill, and it demonstrates the utility of the
      sublethal toxicity tests for monitoring the impact of petroleum spills.

PMID- 16788741
TI  - Evolution of a protein-folding machine: genomic and evolutionary analyses reveal
      three lineages of the archaeal hsp70(dnaK) gene.
AB  - The stress chaperone protein Hsp70 (DnaK) (abbreviated DnaK) and its co
      chaperones Hsp40(DnaJ) (or DnaJ) and GrpE are universal in bacteria and
      eukaryotes but occur only in some archaea clustered in the order 5'-grpE-dnaK
      dnaJ-3' in a locus termed Locus I. Three structural varieties of Locus I, termed
      Types I, II, and III, were identified, respectively, in Methanosarcinales, in
      Thermoplasmatales and Methanothermobacter thermoautotrophicus, and in
      Halobacteriales. These Locus I types corresponded to three groups identified by
      phylogenetic trees of archaeal DnaK proteins including the same archaeal
      subdivisions. These archaeal DnaK groups were not significantly interrelated,
      clustering instead with DnaKs from three bacterial lineages, Methanosarcinales
      with Firmicutes, Thermoplasmatales and M. thermoautotrophicus with Thermotoga,
      and Halobacteriales with Actinobacteria, suggesting that the three archaeal types
      of Locus I were acquired by independent events of lateral gene transfer. These
      associations, however, lacked strong bootstrap support and were sensitive to
      dataset choice and tree-reconstruction method. Structural features of dnaK loci
      in bacteria revealed that Methanosarcinales and Firmicutes shared a similar
      structure, also common to most other bacterial groups. Structural differences
      were observed instead in Thermotoga compared to Thermoplasmatales and M.
      thermoautotrophicus, and in Actinobacteria compared to Halobacteriales. It was
      also found that the association between the DnaK sequences from Halobacteriales
      and Actinobacteria likely reflects common biases in their amino acid
      compositions. Although the loci structural features and the DnaK trees suggested
      the possibility of lateral gene transfer between Firmicutes and
      Methanosarcinales, the similarity between the archaeal and the ancestral
      bacterial loci favors the more parsimonious hypothesis that all archaeal
      sequences originated from a unique prokaryotic ancestor.

PMID- 16788744
TI  - Sediment TCDD-EQs and EROD and MROD activities in Ranid frogs from agricultural
      and nonagricultural sites in Michigan (USA).
AB  - In vitro studies have demonstrated atrazine-mediated induction of 7
      ethoxyresorufin O-deethylase (EROD) activity. EROD is an enzyme active in the
      metabolism of many compounds, including many xenobiotics. These studies have
      suggested that atrazine may affect reproductive function by altering steroid
      metabolism. The goal of this study was to determine whether relationships could
      be detected between measured atrazine concentrations in surface waters and the
      liver-somatic index (LSI) and EROD and 7-methoxyresorufin O-deethylase (MROD)
      activities in the livers of ranid frogs. In addition, sediment dioxin toxic
      equivalents (TCDD-EQs) were determined using the H4IIE-luc cell bioassay. Adult
      and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana), and
      Northern leopard frogs (R. pipiens) were collected from areas with extensive corn
      cultivation and areas where there was little agricultural activity in south
      central Michigan in the summer of 2003. Atrazine concentrations at
      nonagricultural sites ranged from less than the limit of quantification (0.17
      microg atrazine/L) to 0.23 microg atrazine/L and did not exceed 1.2 microg
      atrazine/L at agricultural sites. Sediment TCDD-EQs were measurable only at one
      agricultural site. Of the measured parameters, only LSI values in adult male
      frogs differed significantly between agricultural and nonagricultural sites, with
      greater values observed at agricultural sites. In green frogs, EROD and MROD
      activities were measurable in both adult and juvenile frogs and were similar
      among sites. Median EROD activities ranged from 13 to 21 pmol/min/mg protein in
      adult male green frogs and from 5 to 13 pmol/min/mg protein in adult female green
      frogs. Juvenile frogs had greater EROD and MROD activities than adult frogs.
      Bullfrogs and leopard frogs had greater activities than did green frogs. Atrazine
      concentrations were significantly and negatively correlated with MROD activity in
      adult male green frogs (Spearman R = -0.800). LSI and EROD and MROD activities of
      adult female or juvenile green frogs were not significantly correlated with
      atrazine concentrations. These results suggest that atrazine does not appear to
      have a consistent association with EROD or MROD activities in wild-caught green
      frogs.

PMID- 16788745
TI  - Ammonium toxicity at high pH in a marine bioassay using Corophium volutator.
AB  - Two forms of ammonium exist in water: un-ionized ammonia NH3 and ionized ammonium
      NH4+. The toxicity to many aquatic organisms is primarily attributed to the NH3
      (un-ionized) species, with the NH4+ ion (ionized) species being relatively less
      toxic. The pH level influences the degree of ionization. It is therefore very
      important that quality criteria be derived for total ammonium levels at several
      pH values in order to allow correct interpretation of the sediment bioassay with
      Corophium volutator. The responses of Corophium to total ammonium were studied in
      a series of pH-controlled experiments. The LC50 of total ammonium showed a
      significant decrease with increasing pH, in both water-only and sediment
      experiments. The results indicated a combined NH4+ and NH3 toxicity at pH levels
      less than 8.3. The results can be used to set pH-dependent water quality criteria
      for total ammonium in overlying water in a 10-day sediment bioassay with
      Corophium volutator.

PMID- 16788746
TI  - Distribution of HCHs and DDTs in soils from Beijing city, China.
AB  - Concentrations of HCH isomers, DDT, and its metabolites have been measured in 63
      soil samples collected in the urban area and outskirts of Beijing City. HCHs and
      DDTs were observed in all samples and their geometric mean levels were 5.78 and
      38.21 ng g(-1), respectively. The spatial distribution of OCPs in Beijing was
      clearly showed by the contour map, suggesting the sites with the higher level of
      OCPs are located in the west and the south region and urban areas within the
      study regions." Furthermore, a t-test showed a significant difference of the
      level of some compounds between urban and outskirts areas. The temporal
      distribution of HCHs and DDTs suggested that the historical application of OCPs
      has a great effect on the residual level. The ratios of (alpha-/gamma -HCH (p,p'
      DDE+p,p'-DDD)/p,p'-DDT, and o,p'-DDT/p,p'-DDT indicated the present of lindane
      and impure dicofol besides technical HCHs and technical DDTs in Beijing. The
      potential risk of HCHs and DDTs was assessed on the basis of some current
      guideline values for soil. The level of OCPs in our study area was compared with
      other studies.

PMID- 16788747
TI  - Methylmercury concentrations in fish from tidal waters of the Chesapeake bay.
AB  - Striped bass (Morone saxatilis), white perch (Morone Americana), and largemouth
      bass (Micropterus salmoides) were collected in the Chesapeake Bay mainstem and
      tributaries and analyzed for total mercury (Hg) and methylmercury (MeHg) content.
      Striped bass are anadromous, whereas white perch and largemouth bass are resident
      species, and the largemouth bass are also restricted to the tidal fresh portion
      of the Bay. Total Hg and MeHg concentrations in striped bass increased with fish
      size, and large fish (>7.5 kg wet weight) tended to have MeHg concentrations of
      300 ng g(-1) or greater. On average, the striped bass MeHg concentration was 120
      +/- 100 ng g(-1) and the fraction of the total Hg as MeHg was 65 +/- 22%. Reasons
      for the lower relative MeHg content are discussed. Otolith strontium/calcium
      ratios were also determined to examine whether migration had a significant impact
      on MeHg content in striped bass. Resident fish did appear to have a higher MeHg
      burden than the more migratory fish of similar size. Largemouth bass and white
      perch tended to have low MeHg content (respectively, 14 +/- 7 and 13 +/- 11 ng g(
      1); all fish <1 kg wet weight), and the white perch also had a low %MeHg (28 +/-
      14%), reflecting their mostly planktivorous lifestyle. A comparison of largemouth
      bass and striped bass MeHg concentrations for the estuarine fish with those of
      fish in Maryland reservoirs of similar size showed that the estuarine fish have
      much lower MeHg burdens. Differences in MeHg concentration in the estuarine
      waters compared to the reservoir waters likely account for much of this
      difference, although the importance of other factors is also discussed.

PMID- 16788748
TI  - Risk factors affecting blood PCDDs and PCDFs in residents living near an
      industrial incinerator in Korea.
AB  - The contamination sources of polychlorinated dibenzodioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs), such as industrial incinerators, can
      potentially change the blood levels and isomer patterns of PCDD/DFs in residents
      living near the incinerators. In this study, we estimated whether the blood
      levels and isomer patterns of PCDD/DFs in residents living near an incinerator
      were affected by its presence and investigated factors that characterize the risk
      of high exposure to PCDD/DFs in the area. We estimated the blood levels and
      homologue patterns of PCDD/DFs in a group of 40 residents living within 5 km of
      an industrial incinerator and in a group of 20 residents living 20 km away from
      an incinerator. We cannot assert that the operation of incinerator facilities was
      only cause of increased PCDD/DFs in these residents; however, the operation of
      incinerator facilities in agricultural areas increased PCDD/DF exposure to
      individuals. The group living next to the industrial incinerator especially
      represented the typical isomer pattern in which the proportions of OCDDs were
      lower and those of PCDFs higher than those in the other groups. The high-risk
      population with increased blood levels of PCDD/DFs included those who had lived
      longer in the contaminated area as well as those who frequently ate contaminated
      foods.

PMID- 16788750
TI  - Invasive squamous cell carcinoma of the skin: defining a high-risk group.
AB  - BACKGROUND: Unlike its more common non-invasive form, invasive squamous cell
      carcinoma (SCC) of the skin can be biologically aggressive and is prone to recur.
      The objectives of this study were to identify relevant clinicopathologic
      prognostic factors associated with the outcomes of patients with invasive SCC in
      order to define a high-risk group. METHODS: We retrospectively reviewed the
      records of patients with invasive cutaneous SCC of the trunk or extremities who
      received surgical treatment at a tertiary care cancer center over the past 10
      years. We examined the patterns of presentation, all known clinical and
      histological risk factors for recurrence, and their association with survival.
      RESULTS: 136 patients were identified, of whom 102 (74%) were male. Patterns of
      presentation included primary (n = 91), locally recurrent (n = 16), regional
      nodal (n = 24), and distant (n = 5) disease. Univariate analysis identified
      poorly differentiated carcinomas (hazard ratio [HR] = 2.92, P = .016), scar
      carcinomas (HR = 3.12, P = .008), tumor size > 2 cm (HR = 3.79, P = .006), and
      regional nodal disease (HR = 5.77, P < .0001) as significant risk factors for
      recurrence or death. On multivariate analysis, however, only regional nodal
      disease at presentation (HR = 7.64, P < .0001) was found to be significant.
      CONCLUSIONS: Patients with invasive SCCs metastatic to regional nodes constitute
      a group at high risk for recurrence and death. Such patients should be considered
      for adjuvant therapy trials.

PMID- 16788751
TI  - Prognostic significance of molecular staging study of sentinel lymph nodes by
      reverse transcriptase-polymerase chain reaction for tyrosinase in melanoma
      patients.
AB  - BACKGROUND: We performed this study to evaluate the clinical effect of
      microscopic and submicroscopic metastases in sentinel lymph nodes (SLNs) from
      patients with early-stage melanoma. METHODS: Patients with confirmed cutaneous
      melanoma (American Joint Committee on Cancer stages I and II) underwent standard
      lymphoscintigraphy and SLN biopsy. Serial sections were divided between routine
      histopathology with hematoxylin and eosin plus immunohistochemistry for HMB-45
      and molecular analysis by nested reverse transcriptase-polymerase chain reaction
      (RT-PCR) assay for tyrosinase (using beta-actin as a control). RESULTS: Of 180
      patients analyzed (318 SLNs), 38 (21%) patients had positive SLN(s) by routine
      hematoxylin and eosin and immunohistochemistry (microscopic disease; group 1),
      and 142 (79%) had negative histological results. Analysis by RT-PCR detected
      tyrosinase in at least 1 SLN from 124 (69%) patients. Among patients with
      histologically negative SLN(s), tyrosinase was detected in 86 (48%) patients
      (submicroscopic disease; group 2), whereas 40 (22%) patients had negative results
      by both histology and RT-PCR (group 3). Sixteen (9%) patients had histologically
      negative SLNs and ambiguous RT-PCR results (group 4). Among 138 patients in the
      analysis of recurrence (mean follow-up, 45 months), only 18 patients had a
      recurrence: 11 (31%) of 35 in group 1, 5 (10%) of 51 in group 2, and 2 (5%) of 37
      in group 3. No recurrences were seen in group 4. Only group 1 had a significantly
      shorter disease-free survival and overall survival compared with the other
      groups. CONCLUSIONS: After a long follow-up period, molecular upstaging by
      tyrosinase RT-PCR failed to detect a subgroup of patients with an increased
      probability of recurrence.

PMID- 16788752
TI  - Level of fluorodeoxyglucose uptake predicts risk for recurrence in melanoma
      patients presenting with lymph node metastases.
AB  - BACKGROUND: The incidence of malignant melanoma has increased. Identification of
      additional prognostic factors may allow the development of individualized
      strategies. This multivariate analysis was undertaken to evaluate the potential
      role of the standard uptake value (SUV) in predicting disease-free and overall
      survival in melanoma patients with lymph node metastases. METHODS: All melanoma
      patients with palpable lymph node metastases who where referred for a
      fluorodeoxyglucose positron emission tomography scan were eligible. The SUV in
      the lymph node metastasis was calculated. Data were analyzed (Kaplan-Meier), and
      differences in cumulative survival and the disease-free rate were assessed (log
      rank test). Univariate and multivariate analyses (Cox proportional hazard model)
      were performed to determine independent prognostic factors. RESULTS: There was no
      statistical difference in survival for the 38 patients with a high or low SUVmean
      (P = .11). However, a significant difference was found in disease-free survival
      (P = .03). Ulceration of the primary melanoma (P = .023) was an independent
      predictor of survival. For the disease-free survival, multivariate Cox regression
      showed adjuvant radiation (P = .001), localization of the primary melanoma (P =
      .017), and a high SUVmean (P = .009) as independent prognostic factors.
      CONCLUSIONS: Disease-free survival of melanoma patients was prolonged in those
      with a low SUVmean value (P = .03) in their lymph node metastasis, as compared
      with those with a high SUVmean. However, this difference was not found for
      overall survival. In multivariate analysis, high SUVmean was an independent
      prognostic factor (P = .009) for disease-free survival. Prospective research
      should determine whether patients with a high FDG uptake in melanoma lymph node
      metastases could benefit from adjuvant radiation treatment or chemotherapy.

PMID- 16788753
TI  - The prognostic importance of sentinel lymph node biopsy in thin melanoma.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is prognostically useful in
      patients with cutaneous melanoma with Breslow thickness > 1 mm. The objective of
      this study was to determine whether sentinel node histology has similar
      prognostic importance in patients with thin melanomas (< or = 1 mm). METHODS:
      This was a retrospective study of patients who underwent SLNB for clinically
      localized melanoma at Indiana University Medical Center between 1994 and 2003.
      SLNB results and traditional melanoma prognostic indicators were studied in
      univariate log-rank tests. RESULTS: One hundred eighty-four patients with
      melanomas < or = 1 mm thick underwent SLNB. SLNB was tumor positive in 12
      patients (6.5%). Univariate analysis of SLNB results revealed that Breslow
      thickness, Clark level of invasion, and mitotic index were associated with SLNB
      status. Tumor positivity was observed at different rates in tumor thickness
      subsets: < .75 mm, 2.3%; and .75 to 1.0 mm, 10.2% (P = .0372). Disease-free
      survival and overall survival were significantly associated with SLNB results in
      melanomas < or = 1 mm (log-rank test: P < .0001 and P = .0125, respectively) at a
      median follow-up of 26.3 months. CONCLUSIONS: SLNB histology in melanomas < or =
      1.0 mm deep is a significant predictor of outcome. SLNB should be considered for
      selected patients with melanomas .75 to 1.0 mm.

PMID- 16788754
TI  - Activated Akt and Erk expression and survival after surgery in pancreatic
      carcinoma.
AB  - BACKGROUND: Long-term survival of surgically resectable pancreatic cancer
      patients is uncommon. The epidermal growth factor receptor (EGFR) and the
      phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and
      an understanding of their role in resected cases may help refine adjuvant
      therapy. METHODS: We investigated the expression of EGFR, Erk, Akt, and their
      phosphoforms (p-) in pancreatectomy specimens and correlated these with survival.
      Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were
      included. Immunohistochemical staining of paraffin-embedded blocks was performed
      by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A
      standard immunoperoxidase technique was used to detect the avidin-biotin
      peroxidase complex. Immunostaining was visually scored with the histoscore method
      by two surgical pathologists. RESULTS: Patient characteristics were as follows:
      17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer
      stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV,
      3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17,
      and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6),
      radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry
      revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt
      in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P =
      .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with
      survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8),
      grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2),
      and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival.
      CONCLUSIONS: p-Erk and p-Akt expression may have prognostic and therapeutic
      implications in pancreatic cancer.

PMID- 16788756
TI  - Specific gene-expression profiles of noncancerous liver tissue predict the risk
      for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus
      positive patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection produces chronic hepatitis,
      cirrhosis, and, ultimately, hepatocellular carcinoma (HCC). A molecular analysis
      of the damaged liver tissues infected with HCV may identify specific gene
      expression profiles associated with a risk for liver carcinogenesis. METHODS:
      Forty patients with HCV-positive HCC were classified into two groups: single
      nodular HCC group (n = 28) and multicentric HCC group (n = 12). Using a
      complementary DNA microarray, we compared the gene-expression patterns of the
      noncancerous liver tissue specimens between the two groups. We also identified
      the differentially expressed genes related to multicentric recurrence in the
      liver remnant. We then evaluated whether a specific gene-expression profile can
      accurately estimate the risk for multicentric hepatocarcinogenesis. RESULTS: We
      selected the 230 differentially expressed genes in the multicentric HCC group. A
      hierarchical clustering analysis identified a cluster that might be closely
      associated with the multicentric occurrence of HCC. On the basis of the gene
      expression profiling of the 36 genes commonly associated with both multicentric
      HCC and multicentric recurrence, we created a scoring system to estimate the risk
      for multicentric hepatocarcinogenesis. The prediction score of patients in the
      multicentric HCC group with multicentric recurrence (19.9 +/- 9.2) was
      significantly higher (P < .05) than that in the single nodular HCC group without
      multicentric recurrence (-1.8 +/- 12.7). CONCLUSIONS: Specific gene-expression
      signatures in noncancerous liver tissue may help to accurately predict the risk
      for developing HCC.

PMID- 16788755
TI  - Effects of location and extension of portal vein tumor thrombus on long-term
      outcomes of surgical treatment for hepatocellular carcinoma.
AB  - BACKGROUND: The role of surgical resection and thrombectomy for hepatocellular
      carcinoma (HCC) with portal vein tumor thrombus (PVTT) is controversial. This
      study aimed to evaluate the effects of the location and extent of PVTT on the
      long-term outcomes of surgical treatment for HCC. METHODS: A total of 438
      patients with HCC and PVTT underwent liver resection with or without
      thrombectomy. These 438 patients were divided into 2 groups: in group A, PVTT was
      located in the hepatic resection area or protruded into the first branch of the
      main portal vein beyond the resection line for < 1 cm (286 patients), and in
      group B, PVTT extended into the main portal vein (152 patients). Concomitant
      thrombectomy was performed in 147 patients (51.4%) of group A and in all patients
      of group B. RESULTS: PVTT recurrence within 6 months after surgery in group B was
      significantly higher than that in group A: 76.9% vs. 11.3%. Remnant liver
      recurrence within 1 year after surgery was 45.0% in group A and 78.8% in group B.
      The cumulative 1-, 2-, 3-, and 5-year overall survival rates were 58.7%, 39.9%,
      22.7%, and 18.1% for group A and 39.5%, 20.4%, 5.7%, and 0% for group B,
      respectively. The overall survivals were significantly better in group A than
      group B (P < .02). CONCLUSIONS: Liver resection with thrombectomy yielded better
      outcomes in the HCC patients with PVTT confined to the first or second branch of
      the main portal vein compared with PVTT extending into the main portal vein.

PMID- 16788757
TI  - Surgical outcomes of noninvasive and minimally invasive intraductal papillary
      mucinous neoplasms of the pancreas.
AB  - BACKGROUND: Noninvasive and minimally invasive intraductal papillary-mucinous
      neoplasms (IPMNs) have a favorable surgical outcome. However, cases of recurrent
      noninvasive or minimally invasive IPMN are sometimes encountered, and the
      patterns of the recurrence of those tumors have not yet been fully clarified. In
      this study, we evaluated the surgical outcome of noninvasive and minimally
      invasive IPMNs, concentrating particularly on the pattern of recurrences.
      METHODS: Twenty patients with noninvasive and minimally invasive IPMNs were
      assessed. Resected specimens were evaluated histopathologically with regard to
      the malignant nature of the tumors, the status of the surgical margin, and
      peripancreatic lymph node involvement. Cumulative overall survival rates and
      recurrence after surgery were assessed. RESULTS: Of the 20 patients, 13 had
      benign IPMNs, including adenomas (n = 10) and borderlines (n = 3), and 7 had
      malignant IPMNs, including carcinomas in situ (n = 4) and minimally invasive
      IPMNs (n = 3). Histopathologic examination confirmed the absence of tumor
      involvement in the resected lymph nodes and at the surgical margins. During the
      follow-up period, one patient with minimally invasive IPMN and one patient with
      noninvasive IPMN died of tumor recurrence in the peritoneum that was presumably
      caused by intraoperative manipulation. All of the patients with benign IPMNs
      survived, whereas the 10-year survival rate of the patients with malignant IPMNs
      was 67%. CONCLUSIONS: Surgical resection can offer a favorable outcome for
      noninvasive and minimally invasive IPMNs. Tumor recurrence was observed only in
      the peritoneal cavity. More careful perioperative management concerned with
      peritoneal recurrence should be emphasized for noninvasive and minimally invasive
      IPMNs.

PMID- 16788758
TI  - PIK3CA and TFRC located in 3q are new prognostic factors in esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: Amplification of the chromosome 3q seems to occur frequently in
      esophageal squamous cell carcinoma (ESCC). This study analyzed the clinical
      effect of messenger RNA (mRNA) expression for PIK3CA (the gene that encodes
      phosphatidylinositol-3 kinase catalytic alpha-polypeptide) and TFRC (the gene
      that encodes the transferrin receptor), which map within chromosome 3q in ESCC.
      METHODS: Formalin-fixed, paraffin-embedded ESCC tissues were examined. Total RNAs
      were extracted, and reverse transcription products were subjected to polymerase
      chain reaction amplification of beta-actin, PIK3CA, and TFRC. RESULTS: Expression
      of beta-actin mRNA was detected in 67 (55.8%) of 120 samples, with PIK3CA mRNA
      expression in 22 (32.8%) of these 67 samples and TFRC mRNA expression in 15
      (22.4%) of the 67 samples. PIK3CA mRNA expression correlated with regional lymph
      node metastasis (P = .04). TFRC mRNA expression correlated with distant
      metastasis (P = .04). Patients with positive results for either PIK3CA or TFRC
      mRNA displayed a significantly worse prognosis than patients with negative
      results (PIK3CA, P = .045; TFRC, P = .009). TFRC mRNA expression represented an
      independent prognostic factor in multivariate analysis (P = .0233), but PIK3CA
      did not (P = .7585). CONCLUSIONS: PIK3CA and TFRC mRNA represent prognostic
      factors in patients with ESCC. TFRC mRNA offers an independent prognostic factor,
      and expression may have clinically important implications.

PMID- 16788759
TI  - Initial outcomes for patients treated on the American Society of Breast Surgeons
      MammoSite clinical trial for ductal carcinoma-in-situ of the breast.
AB  - BACKGROUND: The MammoSite device was designed as a breast brachytherapy
      applicator and is currently used to deliver accelerated partial breast
      irradiation (APBI). We hypothesized that APBI delivered with the MammoSite device
      would be well tolerated and be associated with a good cosmetic outcome in
      patients with ductal carcinoma-in-situ (DCIS). METHODS: From 2002 to 2004, 191
      patients with DCIS were enrolled in a registry trial to assess the MammoSite
      applicator. Fifteen patients were excluded from analysis because of device- or
      patient-related factors; 7 patients were excluded after receiving a radiotherapy
      boost, thus leaving 169 patients available for study. Follow-up information was
      available for 158 patients. The average length of follow-up was 7.35 months.
      Forty-three patients had at least 1 year of follow-up. RESULTS: Skin spacing for
      the MammoSite applicator was as follows: < 5 mm, 3 patients (1.78%); 5 to 7 mm,
      18 patients (10.65%); and > or = 7 mm, 148 patients (87.57%). Patients with a
      device-to-skin distance of > or = 7 mm had the best cosmetic result. Patients
      with a device-to-skin distance of > or = 7 mm also had a lower incidence of
      radiation dermatitis. Data on 43 patients who were followed up for at least 1
      year confirmed these findings. Additional adverse events were primarily related
      to skin changes, with breast infections occurring in five patients (3.16%). No
      patient in the study has experienced a recurrence. CONCLUSIONS: APBI delivered
      via MammoSite is well tolerated in patients with DCIS, and the lowest toxicity
      was obtained in patients with the greatest device-to-skin distance. Long-term
      follow-up data regarding patient satisfaction, cosmesis, and efficacy are needed
      and will be determined from a recently opened large randomized study.

PMID- 16788760
TI  - Ethnic disparities in breast cancer management among Asian Americans and Pacific
      Islanders.
AB  - BACKGROUND: Little is known about breast cancer management among Asian Americans
      and Pacific Islanders (AAPI). METHODS: We performed a retrospective analysis of
      2030 women (935 Japanese, 144 Chinese, 235 Filipino, 293 Hawaiian, and 423 white;
      mean age +/- SD, 59 +/- 13 years) with a diagnosis of early breast cancer (stages
      I, II, and IIIA) in Hawaii from 1995 to 2001. We linked data from the
      Surveillance, Epidemiology, and End Results program's Hawaii Tumor Registry to
      administrative health care claims. We evaluated (1) breast-conserving surgery
      (BCS); (2) radiotherapy after BCS; and (3) chemotherapy for node-positive
      disease. We used logistic regression to examine the association between AAPI
      ethnicity and treatment, adjusting for age, year, rural residence, tumor size,
      grade, nodal status, receptor status, prior cancer, comorbidity index, health
      plan type, and income. RESULTS: Overall, 60.3% of women had stage I disease,
      36.8% had stage II, and 2.9% had stage IIIA. Only 55.6% received BCS, and 85.1%
      of these women also received radiation. Of those with nodal involvement (n =
      521), 82.7% received chemotherapy. Japanese and Filipino women were significantly
      less likely than white women to undergo BCS (for Japanese: adjusted odds ratio,
      0.62; 95% confidence interval, 0.48-0.80; for Filipinos: adjusted odds ratio,
      0.47; 95% confidence interval, 0.33-0.66). Filipinos tended to be less likely
      than white women to receive radiation after BCS (adjusted odds ratio, 0.80; 95%
      confidence interval, 0.42-1.49). AAPI women were as likely as white women to
      receive adjuvant chemotherapy for nodal spread. CONCLUSIONS: We found disparities
      in the management of early-stage breast cancer among AAPI women, particularly
      among Japanese and Filipinos. Further study is needed to determine the reasons
      for the observed disparities and to understand their effect on health outcomes.

PMID- 16788761
TI  - Three-axillary lymph node sampling for the prediction of nonsentinel node
      metastases in breast cancer patients with sentinel node metastases.
AB  - BACKGROUND: In half of breast cancer patients with positive sentinel nodes, the
      sentinel nodes are the only metastatic nodes. Such patients have no more
      metastatic nonsentinel nodes and do not need to undergo axillary lymph node
      dissection. The purpose of this study was to investigate whether three-axillary
      lymph node sampling after sentinel node biopsy predicts the status of nonsentinel
      nodes in patients with sentinel node metastases. METHODS: Sentinel node biopsy
      was performed with dye and radioisotope. When the sentinel nodes were diagnosed
      as metastasis positive by using intraoperative imprint cytology, three-axillary
      lymph node sampling was performed, followed by axillary lymph node dissection.
      RESULTS: Of 47 cases with positive imprint cytology, 43 (91%) were diagnosed as
      metastasis positive on their final histological examination and were analyzed.
      The status of the sampled nodes was significantly associated with the status of
      nonsentinel nodes (P < .0001). Six (43%) of 14 patients with positive sampled
      nodes had at least 1 positive remaining node. Only 2 (7%) of 29 patients whose
      sampled nodes were negative were found to have additional nodal metastases. The
      sensitivity, specificity, and accuracy of the sampled nodes for the prediction of
      nonsentinel node metastases were 87.5%, 100%, and 95.3%, respectively.
      CONCLUSIONS: We demonstrated that three-node sampling may be useful for
      predicting the status of nonsentinel nodes and avoiding axillary lymph node
      dissection in patients with only sentinel node metastases.

PMID- 16788762
TI  - Local recurrences after conservative treatment of ductal carcinoma-in-situ of the
      breast without radiotherapy: the effect of age.
AB  - BACKGROUND: The main goal in treatment of ductal carcinoma-in-situ (DCIS) of the
      breast is to prevent local recurrences. Radiotherapy after breast-conserving
      surgery has been shown to decrease the recurrence rate, although whether all
      patients should be treated with radiotherapy remains a topic of debate. The aim
      of this study was to assess the local recurrence rate after conservative surgical
      treatment of DCIS without radiotherapy and to identify risk factors for local
      recurrence. METHODS: A total of 499 female patients with 502 DCIS lesions treated
      in the period 1989 to 2002 were retrospectively reviewed. Survival rates were
      calculated by the Kaplan-Meier method, and differences were tested by using the
      log-rank test. The association of variables with local recurrence was analyzed by
      using the chi2 test. RESULTS: Treatment constituted of lumpectomy in 329 patients
      (65%). Thirty-eight patients (8%) had disease-positive margins, and for 41
      patients (8%) the margin status was not known. Eighty tumors recurred, for a
      local recurrence rate of 13% after 4 years compared with 17% for patients treated
      with breast-conserving surgery only. Risk factors for ipsilateral recurrences
      were younger age (< 50 years), treatment with breast-conserving surgery only, and
      presence of disease-involved surgical margins. CONCLUSIONS: Conservative
      treatment of DCIS results in high recurrences rates, and outcomes can be improved
      by performing more radical surgery. Because radiotherapy has been shown to be
      effective in preventing recurrent disease, and, to date, no subgroups have been
      identified in which radiation can be omitted, its use is recommended, especially
      in younger patients.

PMID- 16788763
TI  - Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and
      survival in stage IV hypopharyngeal cancer.
AB  - BACKGROUND: Eighty percent of hypopharyngeal squamous cell carcinoma patients
      have advanced stages (III and IV) of the disease, and biological markers are
      required to predict high-risk head and neck squamous cell carcinoma patients in
      need of highly aggressive treatments after surgery to improve the survival rate.
      We analyzed the potential prognostic value of galectin 7 in a series of 81 stage
      IV hypopharyngeal SCCs because galectin 7 is an emerging marker involved in the
      epidermal development of pluristratified epithelia and in epidermal cell
      migration. METHODS: The immunohistochemical expression of galectin 7 was
      determined on a series of 81 stage IV hypopharyngeal SCCs and was compared with
      that of galectins 1 and 3. RESULTS: High levels of galectin 7 expression were
      associated with rapid recurrence rates and dismal prognoses in these 81 stage IV
      hypopharyngeal SCCs, a feature not observed with galectin 3 and one observed
      weakly, if at all, with galectin 1. CONCLUSIONS: These data suggest that the
      immunohistochemical determination of galectin 7 expression in the case of high
      risk hypopharyngeal cancers is a meaningful tool to identify patients who should
      benefit from aggressive postsurgical adjuvant therapy after surgery, including
      not only radiotherapy, but also chemotherapy.

PMID- 16788764
TI  - High serum concentrations of Sialyl Lewisx predict multilevel N2 disease in non
      small-cell lung cancer.
AB  - BACKGROUND: The purpose of this study was to analyze the clinical significance of
      serum Sialyl Lewisx (SLX) concentrations as a predictor of N2 disease in patients
      with non-small-cell lung cancer. METHODS: The study included 272 patients with
      non-small-cell lung cancer who underwent pulmonary resection in our institution
      between January 1998 and December 2003. Of 272 patients, the serum concentrations
      of SLX were measured by using a commercially available radioimmunoassay kit.
      RESULTS: The 5-year survival rates of patients with concentrations of SLX > 38
      U/mL and those with lower concentrations were 32% and 69%, respectively (P <
      .0001). The median serum concentration of SLX in patients with multilevel N2 or
      N3, single-level N2, and N0/1 disease were 44, 30, and 27 U/mL, respectively. The
      concentrations of serum SLX in patients with multilevel N2 disease were
      significantly higher than those in patients with single-level N2 or those with
      N0/1 disease (Mann-Whitney U-test; P < .0001). Although the sensitivity of SLX
      for identifying patients with non-small-cell lung cancer was only 24% in all
      patients, the sensitivity of SLX increased as the N-factor increased; the
      sensitivity of N0/1 disease was 15%, that of single-level N2 disease was 22%, and
      that of multilevel N2 or N3 disease was 71%. CONCLUSIONS: High serum
      concentrations of SLX predicted multilevel N2 disease and the associated poor
      outcome. Although the sensitivity of serum SLX is not acceptable for use as a
      screening tumor marker, we suggest that the serum concentration of SLX is useful
      as a staging marker to determine the strategy of treatment.

PMID- 16788765
TI  - A multivariate population density model of the dLGN/PGN relay.
AB  - Using a population density approach we study the dynamics of two interacting
      collections of integrate-and-fire-or-burst (IFB) neurons representing
      thalamocortical (TC) cells from the dorsal lateral geniculate nucleus (dLGN) and
      thalamic reticular (RE) cells from the perigeniculate nucleus (PGN). Each
      population of neurons is described by a multivariate probability density function
      that satisfies a conservation equation with appropriately defined probability
      fluxes and boundary conditions. The state variables of each neuron are the
      membrane potential and the inactivation gating variable of the low-threshold Ca2+
      current I(T). The synaptic coupling of the populations and external excitatory
      drive are modeled by instantaneous jumps in the membrane potential of
      postsynaptic neurons. The population density model is validated by comparing its
      response to time-varying retinal input to Monte Carlo simulations of the
      corresponding IFB network composed of 100 to 1,000 cells per population. In the
      absence of retinal input, the population density model exhibits rhythmic bursting
      similar to the 7 to 14 Hz oscillations associated with slow wave sleep that
      require feedback inhibition from RE to TC cells. When the TC and RE cell
      potassium leakage conductances are adjusted to represent cholingergic
      neuromodulation and arousal of the network, rhythmic bursting of the probability
      density model may either persists or be eliminated depending on the number of
      excitatory (TC to RE) or inhibitory (RE to TC) connections made by each
      presynaptic cell. When the probability density model is stimulated with constant
      retinal input (10-100 spikes/sec), a wide range of responses are observed
      depending on cellular parameters and network connectivity. These include
      asynchronous burst and tonic spikes, sleep spindle-like rhythmic bursting, and
      oscillations in population firing rate that are distinguishable from sleep
      spindles due to their amplitude, frequency, or the presence of tonic spikes. In
      this context of dLGN/PGN network modeling, we find the population density
      approach using 2,500 mesh points and resolving membrane voltage to 0.7 mV is over
      30 times more efficient than 1,000-cell Monte Carlo simulations.

PMID- 16788767
TI  - (AAT)n repeat in the cannabinoid receptor gene, CNR1: association with
      schizophrenia in a Spanish population.
AB  - The cannabinoid receptor 1 gene (CNR1) has been associated with addictive
      disorders and schizophrenia in different studies. We have compared the
      frequencies of the alleles for the 3'-UTR CNR1 microsatellite in a sample of 113
      Spanish schizophrenic patients, including 68 with comorbid substance abuse, and
      111 healthy controls. We report that the frequency of the allele 4 of this
      microsatellite is significantly lower in schizophrenia patients when compared
      with controls (chi(2) = 7.858; df 1; P = 0.005). No differences have been found
      with respect to substance abuse.Thus, the allele 4 represents, in our sample, a
      protective factor against schizophrenia (odds ratio 0.468, 95% confidence
      interval (CI) 0.27-0.79). The population attributable genetic risk for the allele
      4 absence is 30% (95% CI = 17-41%) and the attributable risk for the allele 4
      absence in those with schizophrenia is 53% (95% CI = 20-73%). Our results suggest
      that, independent of substance abuse, differences in the cannabinoid system
      function could be involved in the vulnerability to schizophrenia in Spanish
      population.

PMID- 16788768
TI  - Neuroleptic drugs in the human brain: clinical impact of persistence and region
      specific distribution.
AB  - After discontinuation of neuroleptic agents, their effects are still present for
      a long time. The exact underlaying mechanisms are still unclear. In two previous
      studies we measured the concentrations and region-specific distribution of
      haloperidol (Kornhuber et al. 1999) and levomepromazine (Kornhuber et al. 2006)
      in postmortem human brain tissues. The aim of the present paper is to compare the
      results of these two studies. Even after short-term treatment, haloperidol and
      levomepromazine concentrations reach high levels in human brain tissue.
      Haloperidol concentrations in brain tissue are 10-30 times higher than the
      optimum serum concentrations in the treatment of schizophrenia. The brain-to
      blood concentration ratio of levomepromazine is about 10. The estimated
      elimination half-life of these drugs in brain tissue are 6.8 days (haloperidol),
      7.9 days (levomepromazine) and 27.8 days for the metabolite desmethyl
      levomepromazine, respectively. After two half-lives (about 2 weeks), a
      considerable amount of drug remains in brain tissue. Haloperidol concentrations
      appeared to be homogeneously distributed across different brain areas, whereas
      levomepromazine shows a region-specific distribution, with highest values in the
      basal ganglia. The persistence of neuroleptic drugs in the human brain might
      explain their prolonged effects and side effects. The region-specific
      distribution of levomepromazine may increase our understanding of both the
      preferential toxicity of neuroleptic drugs against basal ganglia structures and
      higher basal ganglia volumes in patients treated with neuroleptics.

PMID- 16788769
TI  - Gender- and violence-related prevalence of mental disorders in prisoners.
AB  - OBJECTIVES: To clarify the prevalence of mental diseases including personality
      disorders in a sample of German prisoners regarding delinquency and gender
      specificity. METHOD: Crime history, present state and lifetime mental disorders,
      as well as personality disorders, were assessed amongst 415 inmates and compared
      regarding gender and type of delinquency. RESULTS: Female offenders more often
      committed homicide while male offenders more frequently committed assault and
      robbery. Men had a higher prevalence of alcohol abuse and dissocial PD while
      women more often showed depression, anxiety disorders and Borderline PD. Violent
      offences were related to a higher prevalence of alcohol abuse and dissocial PD,
      as well as higher comorbidities of mental disorders. CONCLUSION: Results
      emphasize the complexity of the needs and requirements of imprisoned offenders.
      Our findings reveal an urgent need for psychiatric-psychotherapeutic services to
      provide suitable care to inmates in order to contribute to a more favorable legal
      prognosis.

PMID- 16788770
TI  - Obstetric complications and neurological abnormalities in neuroleptic-naive
      psychotic patients.
AB  - Studies addressing the relationship between a history of obstetric complications
      (OCs) and neurological abnormalities in schizophrenia have produced contradictory
      findings. Using a pre-posttreatment design in a neuroleptic-naive sample of
      psychotic patients, we examined the relationship of a history of OC to primary
      and drug-induced neurological signs. Fifty neuroleptic-naive non-affective
      psychotic inpatients were assessed for a history of OC by using the McNeil
      Sjostrom scale, and for neurological signs including parkinsonism, dyskinesia,
      akathisia and catatonia, which were rated before and after inception of
      neuroleptic treatment. A subsample of 28 patients were also examined for
      neurological soft-signs. Ratings of OCs were related to admission levels of
      parkinsonism, dyskinesia, akathisia and neurological soft-signs, but not to
      levels of catatonia. By obstetric period, pregnancy complications were related to
      levels of parkinsonism, dyskinesia, and neurological soft-signs, and neonatal
      complications were related to levels of akathisia. Drug-induced neurological
      signs were not associated with a history of OCs. We argue that the association
      pattern between a history of OCs and primary neurological signs from several
      domains suggests a causal link among these variables. Having a history of OCs
      does not convey a vulnerability for developing drug-induced neurological signs in
      the short term.

PMID- 16788771
TI  - The quality of life of the mentally ill living in residential facilities:
      findings from a national survey in Italy.
AB  - Quality of Life (QOL) is an outcome measure particularly useful to assess the
      effects of deinstitutionalization policies. To date no large-scale study has been
      conducted in residential facilities (RFs). Participants included 1492 subjects
      living in 174 RFs (20% of the total) randomly sampled in 15 Italian regions.
      Assessment instruments included the WHOQOL-Bref, the GAF, and the Physical Health
      Index (PHI). WHOQOL scores of residents were compared with those of healthy
      subjects (N = 65) and outpatients with schizophrenia (N = 162). Multivariate
      analyses were used to examine the relationship between selected patients'
      characteristics and WHOQOL scores. Mean WHOQOL scores of residents were similar
      to those of outpatients with schizophrenia, and substantially lower than those of
      healthy controls. Lower scores on WHOQOL domains were associated with
      schizophrenia and non-affective psychoses, unipolar depression, anxiety or
      somatoform disorders, shorter duration of illness, positive, negative or mood
      symptoms, lower GAF scores, no participation in internal activities, and PHI
      score. Our findings are consistent with previous studies. The present study
      highlights a marked difference between patients in RFs and healthy controls in
      the social domain. This suggests the need of well-designed rehabilitation plans,
      tailored to patients' needs, to foster the development of their independence and,
      ultimately, improve their QOL.

PMID- 16788773
TI  - An alternative clinical postural stability test for patients with Parkinson's
      disease.
AB  - We compared the sensitivity and consistency of a new Push and Release Test versus
      the Pull Test (item 30 of the Unified Parkinson's Disease Rating Scale; UPDRS) as
      clinical measures of postural stability. Subjects with Parkinson's disease and
      age-matched control subjects participated in 3 protocols investigating: (1) the
      sensitivity and specificity of the two tests related to the subjects' balance
      confidence, as measured by the Activities-specific Balance Confidence (ABC)
      scale, (2) the inter-rater reliability of the two tests, and (3) the consistency
      of the perturbation forces applied to the subjects by each balance test. As a
      test for concurrent validity, the balance tests were also compared with the
      subjects' retrospective reports of fall frequency. Compared with the Pull Test,
      the Push and Release Test was more sensitive to subjects with low balance
      confidence, but less specific for subjects with high balance confidence. The
      inter-rater correlations were higher with the Push and Release Test. Examiners
      applied more consistent perturbation forces to the subjects with the Push and
      Release Test than with the Pull Test. The Push and Release Test correlated better
      with self-reported falls. Therefore, the Push and Release Test provided a more
      sensitive and consistent test of postural stability than the Pull Test.

PMID- 16788772
TI  - Cognitive functioning in the early course of first-episode schizophrenia spectrum
      disorders: timing and patterns.
AB  - OBJECTIVE: The aim of this study was to examine possible cognitive changes
      throughout the early course of schizophrenia spectrum disorders. METHOD: Forty
      two patients, aged 15-50 years, admitted to a first episode psychosis program
      (PAFIP) serving to the community of Cantabria (Spain) and 43 healthy volunteers
      completed a brief battery of five neurocognitive tests at four time-points over 3
      months. The cognitive testing comprise five domains: attention, visuomotor speed,
      declarative memory, working memory and executive function. Baseline assessment
      occurred within 72 hour after the initiation of standard pharmacological
      treatment, and after then parallel forms of the tests were applied at week-2,
      week-6, and month-3. RESULTS: Patient scores showed a significant impairment
      compared to healthy volunteers in the five cognitive domains at baseline and week
      2 assessments. After the first 3 months of antipsychotic treatment, the patient
      group performance reached healthy volunteers level on executive function (Stroop
      interference) and immediate verbal memory tests. In contrast, performance on
      working memory, sustained attention, visuomotor speed, and verbal memory delayed
      recall domains still remained below healthy volunteers, although visuomotor
      processing speed showed a significant improvement. CONCLUSION: Schizophrenia
      spectrum patients show heterogeneous patterns and degrees of cognitive changes
      that contribute to stress the importance of when, what, and how neurocognitive
      functioning in the early phases of the illness is evaluated.

PMID- 16788775
TI  - Subjective visual vertical (SVV) determined in a representative sample of 15
      patients with pusher syndrome.

PMID- 16788776
TI  - Increased mRNA levels of the mitochondrial complex I 75-kDa subunit. A potential
      peripheral marker of early onset schizophrenia?
AB  - Recently, the dopamine D3-receptor mRNA on blood lymphocytes and platelet
      mitochondrial complex I were suggested as biological markers of schizophrenia in
      adults. We investigated the mRNA level of the dopamine D3-receptor and complex I
      subunits in whole blood cells of early-onset schizophrenic patients compared to
      healthy controls using quantitative real-time PCR. We found an increased mRNA
      expression of the complex I 75-kDa subunit (referred to beta-actin in
      schizophrenic patients (0.57 +/- 0.24 versus 0.23 +/- 0.18 in controls, P <
      0.01)), but were unable to analyse the dopamine D3-mRNA expression. This increase
      appears to be inherent to schizophrenia, because it was found in neuroleptic
      naive patients and it was not affected by neuroleptic treatment. Our preliminary
      findings suggest the mitochondrial complex I as a potential peripheral marker of
      schizophrenia and its involvement in the pathophysiology of this illness.

PMID- 16788774
TI  - Subthalamic nucleus stimulation in Parkinson's disease : anatomical and
      electrophysiological localization of active contacts.
AB  - OBJECTIVES: 1 - To assess the anatomical localization of the active contacts of
      deep brain stimulation targeted to the subthalamic nucleus (STN) in Parkinson's
      disease patients. 2 - To analyze the stereotactic spatial distribution of the
      active contacts in relation to the dorsal and the ventral electrophysiologically
      defined borders of the STN and the stereotactic theoretical target. METHODS:
      Twenty-eight patients underwent bilateral high-frequency stimulation of the STN
      (HFS-STN). An indirect anatomical method based on ventriculography coupled to
      electrophysiological techniques were used to localize the STN. Clinical
      improvement was evaluated by Unified Parkinson's Disease Rating Scale motor score
      (UPDRS III). The normalized stereotactic coordinates of the active contact
      centres, dorsal and ventral electrophysiologically-defined borders of the STN
      were obtained from intraoperative X-rays images. These coordinates were
      represented in a three-dimensional stereotactic space and in the digitalized
      atlas of the human basal ganglia. RESULTS: HFS-STN resulted in significant
      improvement of motor function (62.8%) in off-medication state and levodopa
      equivalent dose reduction of 68.7% (p < 0.05). Most of the active contacts
      (78.6%) were situated close to (+/- 1.6 mm) the dorsal border of the STN (STN
      DB), while 16% were dorsal and 5.4% were ventral to it. Similar distribution was
      observed in the atlas. The euclidean distance between the STN-DB distribution
      center and the active contacts distribution center was 0.31 mm, while the
      distance between the active contacts distribution center and the stereotactic
      theoretical target was 2.15 mm. Most of the space defined by the active contacts
      distribution (53%) was inside that defined by the STN-DB distribution.
      CONCLUSION: In our series, most of the active electrodes were situated near the
      STN-DB. This suggests that HFS-STN could influence not only STN but also the
      dorsal adjacent structures (zona incerta and/or Fields of Forel).

PMID- 16788777
TI  - [Advances in the pathogenesis of atopic dermatitis].
AB  - The incidence of atopic dermatitis (AD) is noticeably increasing in
      industrialized countries. New insights into the pathogenesis of this disease are
      mirrored by a changed terminology suggested by the World Allergy Organization: a
      distinction between a so-called atopic and non-atopic dermatitis. The
      pathogenesis of the AD, which this article concentrates on, is highly complex.
      Genetic and environmental factors play a pivotal role in triggering AD. The
      complex pattern of cytokines and chemokines, reflecting a deviated immune
      response in AD patients, is a focus of research, as are the involvement of
      various cells and the epidermal barrier. Research concerning T cells with
      regulatory features as well as IgE-mediated autoreactivity will soon give insight
      into the defective tolerance of atopic patients and might possibly lead to new
      concepts in the management of the disease.

PMID- 16788778
TI  - [Maintenance therapy of psoriasis].
AB  - Maintenance therapy in the interval between flares is an essential part of the
      therapeutic approach to psoriasis. The therapeutic effectiveness of maintenance
      therapy results from a positive influence on the physicochemical characteristics
      of individual compartments of the skin, especially the stratum corneum and the
      epidermis. The objective is revert from a pathological milieu toward a
      physiological one. These effects may be supplemented by pharmacological or
      biochemical effects of the active substances or substance mixtures. Focal points
      are the use of lipophilic bases as well as keratoplastic, antiseptic and
      antipruriginous additives.

PMID- 16788779
TI  - [Erythema induratum Bazin. "Tuberculid" or tuberculosis?].
AB  - A 66-year-old woman presented with erythematous nodules on both legs and told of
      a history of lymph node tuberculosis that had been treated with surgery and
      tuberculostatic therapy years before. A biopsy taken from a nodule showed nodular
      vasculitis. PCR for Mycobacterium tuberculosis-specific DNA on the paraffin
      embedded tissue was positive. Based on the experience with our patient, positive
      PCR results for Mycobacterium tuberculosis-specific DNA in lesions of nodular
      vasculitis are discussed critically. The historical background of "tuberculids",
      such as erythema induratum Bazin, is elucidated.

PMID- 16788780
TI  - [Cartilage cell transplant: surgical technique with matrix-associated
      chondrocytes].

PMID- 16788781
TI  - [A painless technique for reposition of anterior shoulder dislocation].
AB  - Acute shoulder dislocation is a common injury and characterized by an extremely
      painful lack of motion. The treatment objective after diagnosis is immediate
      reduction avoiding additional pain and complications. Various techniques have
      been described for more than 2000 years mostly using traction-countertraction,
      particularly combined with special positioning and leverage maneuvers. We report
      a reduction technique which is performed by a single person with the patient
      sitting on a chair and the physician standing behind him at the affected side.
      Positioning one fist in the anterior part of the axillary fossa for
      countertraction but avoiding direct pressure into the axillary fossa, the other
      hand uses traction grasping the patient's forearm. Only gentle traction is
      maintained until muscle relaxation is achieved and reduction mostly happens in
      this moment. Otherwise slow external rotation of the fist placed in the axilla
      can relieve reduction pushing the humeral head laterally. Additional leverage
      maneuvers are not necessary. This technique was successful in 98 of 108 (90.7%)
      patients. Only in 16.3% was premedication (intravenous analgesics) used. In ten
      patients general anesthesia was required to achieve reduction. No complications
      occurred in any of the patients. The reported technique allows a gentle and
      painless reduction of acute anterior shoulder dislocation with a high success
      rate mostly avoiding premedication.

PMID- 16788783
TI  - [Not "only" a dislocation of the hip: functional late outcome femoral head
      fractures].
AB  - BACKGROUND: Traumatic hip dislocation combined with fracture of the femoral head
      is a rare condition for which little known in terms of long-term prognosis. The
      aim of the retrospective study presented here was to evaluate the clinical and
      radiological outcome of this specific injury. PATIENTS AND METHODS: In a 23 year
      period, 18 patients (17 male) with an average age of 25.6 (range 15-55 years)
      were treated. There were four type-I, three type-II, no type-III, and 11 type-IV
      fractures according to the Pipkin classification (1957). RESULTS: The average
      time to sufficient reduction was 136 min (60-420 min), two by open means. A total
      of 16 patients were operated for open reduction and internal fragment fixation,
      13 through a dorsal approach. All patients filled out a standardized
      questionnaire, and clinical and radiological examinations were also carried out
      on average 12.6 years (range 59-247 months) after injury. Four scoring systems
      were used to classify the outcome: Thompson and Epstein (1951): very good = 1,
      good = 10, fair = 4, poor = 3; Merle D'Aubigne (1954): very good = 9, good = 5,
      fair = 0, poor = 4; Harris (1969): Pipkin I = 81 points, Pipkin II = 97 points,
      Pipkin IV = 73 points (mean); Brooker (1973): grade I = 5, grade II = 1, grade IV
      = 2. CONCLUSION: Quality of life was not reduced in most patients in the long
      term, however three of four patients suffering Pipkin type-IV fractures developed
      functional restrictions with poor results. We conclude that acute reduction of
      the dislocated joint and anatomical reconstruction of the femoral head instead of
      primary hip replacement may end in good to excellent results in type-I and type
      II fractures. Due to the young age of these patients, joint reconstruction should
      always be the first choice even in type-IV fractures with a higher probability of
      poor prognosis.

PMID- 16788784
TI  - [B-cell lymphoma of the testes].
AB  - The occurrence of primary non-Hodgkin's lymphomas of the testes is described in
      just a few studies in the urological literature. The clinical symptomatology and
      especially the treatment concept for this relatively rare tumor entity are hardly
      discussed. Imaging diagnostics, e.g., with CT or MRI, play a decisive role in
      determining the diagnosis and whether a primary testicular disease is involved or
      a generalized systemic disease. In cases of primary B-cell lymphomas of the
      testes, a high inguinal orchiectomy should be performed for diagnostic and
      therapeutic purposes. The standard chemotherapy for aggressive non-Hodgkin's
      lymphomas is the CHOP regimen consisting of cyclophosphamide, doxorubicin,
      vincristine, and prednisone. This article presents two adults aged 67 and 75
      years with histologically proven B-cell lymphoma of the testes and discusses the
      characteristics of this relatively rare clinical picture as well as treatment and
      prognosis.

PMID- 16788782
TI  - [Bipolar dislocation injury of the forearm].
AB  - Bipolar dislocation injury of the forearm is rarely documented. It is a combined
      forearm injury with trauma on the elbow side and on the side of the wrist joint.
      We describe two different cases of this complex dislocation. The first patient
      suffered from a Monteggia-like dislocation fracture with transscaphoid
      dislocation of the wrist. The second person had an acute longitudinal radioulnar
      membrane dissociation after elbow dislocation with an additional scapholunate
      tendon rupture. The difficult management of these injuries is illustrated by
      these cases.

PMID- 16788786
TI  - [Innovative approaches in prostate cancer ultrasound].
AB  - Today, systematic random biopsies have virtually replaced ultrasound as an
      imaging tool in the early diagnosis and staging of prostate cancer. Transrectal
      ultrasonography (TRUS) is now utilized almost only to guide the biopsy needle
      into the correct anatomical or topographical region of the prostate.
      Nevertheless, a large number of clinically significant carcinomas are not
      discovered despite of multiple systematic biopsies. This has led to a dramatic
      increase in the number of biopsy samples taken, with 6, 10, 12 to 143 being taken
      during one session depending on the site. Newer modalities and innovative
      techniques are being investigated in order to accurately identify patients with
      prostate cancer at different stages of the disease. Innovative ultrasonography
      techniques may improve the diagnosis and staging of current imaging techniques.

PMID- 16788787
TI  - [MR techniques for noninvasive diagnosis of prostate cancer].
AB  - The diagnosis of prostate cancer is suggested on the basis of an elevated PSA
      level, abnormal digital exam, and abnormal transrectal ultrasound. US-guided
      biopsy is used to confirm the diagnosis, but up to 30% of prostate cancer may be
      missed with this approach. Meanwhile MR imaging and proton MR spectroscopy have
      emerged as the most sensitive additional tools for the noninvasive evaluation of
      prostate cancer. This article reviews the clinical indications for MRI of the
      prostate and summarizes new techniques such as high field strength (3 tesla) and
      dynamic contrast-enhanced MRI.

PMID- 16788788
TI  - [Advancement of PET and PET/CT in prostate carcinoma].
AB  - Functional imaging of prostate carcinoma was examined with the metabolic
      substrates 2-(18)F-fluorodeoxyglucose, (11)C-methionine, (18)F
      fluorodihydrotestosterone, (11)C-acetate and (11)C/(18)F-choline. Based on
      upregulated enzymes of phospholipid metabolism in prostate carcinoma, (11)C/(18)F
      choline is preferentially incorporated into phosphatidylcholine of membrane
      lipids of prostate cancer cells. PET allows sensitive detection of the
      (11)C/(18)F-choline signal and PET/CT fusion imaging enables intraprostatic
      signal localisation. Most published studies report a high detection rate of
      prostate carcinoma with (11)C/(18)F-choline PET/CT. Differentiation of prostate
      carcinoma from benign hyperplasia and from focal chronic prostatitis may be
      difficult; acute prostatitis accumulates (11)C/(18)F-choline with an intensity
      comparable to prostate carcinoma.

PMID- 16788789
TI  - [High-dose rate brachytherapy for high-risk prostate cancer].
AB  - To estimate disease-free survival it is necessary to allocate patients into tumor
      risk groups: locally advanced prostate carcinoma with extracapsular spread or
      localized prostate carcinoma of tumor stage T2c or one of the risk factors PSA
      >20 or Gleason > or =8 apply for the high-risk group. Intermediate-risk
      carcinomas are those belonging to tumor stage T2b or with PSA >10-20 or Gleason
      7. Particularly for patients with intermediate and high-risk disease early PSA
      relapse is of major interest. This phenomenon could be a consequence of current
      inadequate imaging of lymph node or bone metastasis or as a consequence
      subclinical metastatic spread remains undetectable during radical treatment.
      However, tumor biology itself could lead to the progression of the disease in the
      high-risk group. As a consequence, risk-adapted therapy is very important in
      these cases. The applied radiation dose plays an important role in radiotherapy.
      Several publications have shown that the biochemical relapse correlates with the
      generally accepted risk factors and the radiation dose. Regarding this, high
      quality treatment planning and HDR brachytherapy combined with EBRT (external
      beam radiation therapy) leads to good treatment results in selected groups. So
      far in our own experience, HDR brachytherapy in combination with EBRT is a
      successful form of treatment with few acute and late side effects in the first 42
      patients examined. First results concerning to PSA relapse-free time, quality of
      life, miction, and erectile function are promising.

PMID- 16788791
TI  - [The development of urine diagnostics and its visualisation in "frames"].
AB  - The development of urine diagnostics has been well examined historiographically.
      However, its importance for science studies has not yet been stressed enough. As
      a diagnostic tool, that survived many centuries, it underwent several changes.
      Therefore, its use for science studies is exemplarily displayed in this paper. An
      attempt is made by the authors to combine questions of the history of science
      with methods from the cognitive sciences. The reader is introduced into an
      interdisciplinary approach aiming at the visualisation of scientific shifts to
      make a deeper analyse of such shifts possible. Lawrence Barsalou proposed a
      dynamic frame model to represent cognitive structures. This model is used to
      reconstruct scientific revolutions (in the sense of Thomas Kuhn) as well as
      barely noticeable shifts (in the sense of Ludwik Fleck's shifting thought
      styles). The value of this approach for the history of medicine in general and
      the history of uroscopy in special is discussed.

PMID- 16788792
TI  - [Thirteenth Pediatric Urology Symposium, Eschweiler, 25 March 2006].

PMID- 16788793
TI  - [Satellite congress. Twenty-first Annual Congress of the European Association of
      Urology 2006. Paris].

PMID- 16788794
TI  - [Legal (liability) aspects of PSA determination].

PMID- 16788795
TI  - [Success and failure in interdisciplinary studies].
AB  - The Association of Uro-genital Oncology (AUO) and the Association of Radiological
      Oncology (ARO) proceeded three studies on the indication of prostate cancer
      within the last 10 years. In this article, one of the leading study investigators
      is presenting determines on success or failure of this interdisciplinary studies.

PMID- 16788797
TI  - [Clinical and immunohistochemical findings of intra- and extraoral
      angiosarcomas].
AB  - PURPOSE: A clinico-pathologic study of typical symptoms of intra- and extraoral
      angiosarcomas and clinical course under therapy is presented as well as an
      analysis of the immunohistochemical differential diagnosis of the tumour specific
      formed spaces. PATIENTS AND METHODS: Four male patients aged 63-78 years suffered
      from angiosarcomas of the maxillary sinus, the bucca (two patients) and the
      alveolar ridge of the lower jaw. HISTOPATHOLOGY: For comparative analysis
      paraffin embedded tissue of the initial biopsies was available. The slides were
      stained with standardized H&E, PAS and Gomorri. For standardized
      immunohistochemistry following primary antibodies were applied: monoclonal
      antibodies to pancytoceratin clones AE1/AE3, alpha-smooth-muscle-actin clone 1A4,
      CD31 clone JC/70A, factor-VIII-related antigen clone F/86, Fli-1 (polyclonal,
      Zymed, USA), tenascin-C: BC4 (Prof. L. Zardi), oncofetal glucosylated fibronectin
      clone FDC6 (ACCR), laminin-5: D4B5. Detection using AP-ChemMate and Autostainer
      (Dako, Denmark). RESULTS: While the benign appearance of the lesions resulted
      primarily in wrong diagnoses the histopathologic examination of the biopsies
      revealed the characteristic pattern of angiosarcomas. Wide surgical excision,
      radiotherapy and/or antiangiogenic chemotherapy could not prevent tumour
      progression and death within two and a half years after primary diagnosis. All
      angiosarcomas reacted partially positive for factor-VIII-related antigen and
      CD31. The tumour associated structural defect of vascular lamina with partial
      loss of pericytes/vascular smooth muscle cells was identified
      immunohistochemically by alpha-smooth-muscle-actin and for the first time by
      tenascin-C. CONCLUSIONS: (1.) The variable presentation and the benign appearance
      of oral and perioral angiosarcomas may often delay diagnosis. Oral and perioral
      angiosarcomas show poor prognosis despite of multimodal therapy. (2.) Cytoceratin
      and laminin-5-positivity as typical epithelial antigens don't exclude
      angiosarcoma. Factor-VIII-related antigen, CD31 as well as Fli-1 identify
      angiosarcoma. (3.) alpha-smooth-muscle-actin and the loss of the tenascin-C
      matrix indicate immunohistochemically the characteristic sarcomatous defect of
      differentiation.

PMID- 16788798
TI  - Identification of simple sequence repeat markers for utilizing wide-compatibility
      genes in inter-subspecific hybrids in rice (Oryza sativa L.).
AB  - Although pronounced heterosis in inter-subspecific hybrids was known in rice for
      a long time, its utilization for hybrid rice breeding has been limited due to
      their hybrid sterility (HS). For the last two decades, however, a few inter
      subspecific hybrids have been developed by incorporating wide-compatibility genes
      (WCG) that resolve HS, into parental lines of these inter-subspecific hybrids.
      For effective use of WCG, it is necessary to find convenient markers linked to
      WCG of practical importance. In this paper, initially a set of simple sequence
      repeat (SSR) markers in the vicinity of known WCG loci identified based on
      comparative linkage maps have been surveyed in a population derived from the
      three-way cross- IR36/Dular//Akihikari, where a known donor of WCG Dular was
      crossed to a representative indica and japonica cultivar. Of the five parental
      polymorphic markers, RM253 and RM276 were found to be closely linked to the WCG
      locus S5 at a distance of 3.0 and 2.8 cM, respectively. Later, loci for HS were
      examined in three F(2) populations derived from inter-subspecific crosses, with
      same set of SSR markers. The locus S8 was confirmed to have major influence on HS
      in the F(2 )population derived from CHMRF-1/Taichung65 since two SSR markers in
      its vicinity, RM412 and RM141, co-segregated with HS at a map distance of 7.6 and
      4.8 cM, respectively. In the F(2) population derived from the cross
      BPT5204/Taipei309, three SSR markers in the vicinity of S5, RM50, RM276 and RM136
      co-segregated with HS at a map distance of 4.2, 3.2 and 7.8 cM, respectively. In
      the third F(2 )population derived from Swarna/Taipei309, the SSR markers in the
      vicinity of S5, RM225, RM253, RM50, RM276 and RM136 were identified to co
      segregate with HS at a map distance of 3.2, 2.6, 3.4, 2.6 and 6.6 cM,
      respectively. These results indicated a clear picture of WCG in Dular as well as
      the predominant role of HS alleles at S5 locus. The identified SSR markers are
      expected to be used for incorporation of WCG into parental lines in hybrid rice
      breeding to solve HS in inter-subspecific hybrids.

PMID- 16788796
TI  - [Benign prostatic syndrome (BPS). Ablative treatments].
AB  - Today, the surgical treatment of the benign prostatic syndrome (BPS) often
      follows a course of drug treatment. Besides conventional transurethral resection
      of the prostate (TURP), which has represented the standard therapeutic option for
      decades, and its in part significant modifications ("vaporizing resection";
      bipolar resection), much of the interest has shifted to alternative instrumental
      procedures like transurethral microwave therapy (TUMT), transurethral needle
      ablation of the prostate (TUNA) or several laser techniques. By reviewing the
      current literature, preferably from randomized controlled trials, these different
      procedures are critically assessed. Moreover, the present role of open
      prostatectomy is discussed.

PMID- 16788800
TI  - Comment on: Evans JM, Ogston SA, Emslie-Smith A, Morris A (2006) risk of
      mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of
      patients treated with sulfonylureas and metformin. Diabetologia 49:930-936.

PMID- 16788799
TI  - Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese
      subjects with impaired glucose tolerance: a 5-year follow-up study.
AB  - AIMS/HYPOTHESIS: Polymorphisms of the gene encoding adiponectin (ADIPOQ) have
      previously been associated with type 2 diabetes in Europid and Japanese subjects,
      but not in Pima Indians. The aim of this study was to determine the contribution
      made by ADIPOQ gene variants to glycaemic status in southern Chinese individuals.
      SUBJECTS AND METHODS: Sixty unrelated subjects were screened for single
      nucleotide polymorphisms (SNPs) in the ADIPOQ gene by direct sequencing. The
      association of tagging SNPs with the outcome of glycaemic status in 262 subjects
      with impaired glucose tolerance (IGT) was examined in a 5-year prospective study.
      RESULTS: We identified 15 polymorphisms in the ADIPOQ gene, ten of them
      constituting the tagging SNPs. At 5 years, 39.7% of the subjects with IGT had
      regressed to NGT, 41.2% had persistent IGT or impaired fasting glucose and 19.1%
      had developed diabetes. Only the T45G polymorphism was associated with persistent
      hyperglycaemia at 5 years (p=0.001). Haplotypes formed by the addition of other
      SNPs, as haplotype blocks or pairs, did not confer greater association than T45G
      alone. On logistic regression analysis, T45G independently predicted persistent
      hyperglycaemia at 5 years (OR=2.25, 95% CI 1.29-3.95, G carriers vs TT; p=0.005).
      It also predicted persistent hyperglycaemia in a nested case-control study
      involving 158 sex- and age-matched controls with persistent NGT (p=0.012,
      adjusted for BMI), and that of diabetes or glycaemia progression (p<0.05) in a
      meta-analysis that also included two published studies in Europid subjects.
      CONCLUSIONS/INTERPRETATION: Our findings support a significant role of this
      common ADIPOQ gene polymorphism in predicting glycaemic status in southern
      Chinese people.

PMID- 16788801
TI  - Overproduction of intestinal lipoprotein containing apolipoprotein B-48 in
      Psammomys obesus: impact of dietary n-3 fatty acids.
AB  - AIMS/HYPOTHESIS: Emerging evidence underscores the important role of the small
      intestine in the pathogenesis of dyslipidaemia in insulin resistance and type 2
      diabetes. We therefore tested the hypothesis that n-3 fatty acids improve the
      various events governing intra-enterocyte lipid transport in Psammomys obesus
      gerbils, a model of nutritionally induced metabolic syndrome. MATERIALS AND
      METHODS: Experiments were carried out on Psammomys obesus gerbils that were
      assigned to an isocaloric control diet and a diet rich in fish oil for 6 weeks.
      RESULTS: Increased dietary intake of fish oil lowered body weight and improved
      hyperglycaemia and hyperinsulinaemia. It simultaneously decreased de novo
      intestinal lipogenesis and lipid esterification of the major lipid classes, e.g.
      triglycerides, phospholipids and cholesteryl esters, particularly in insulin
      resistant and diabetic animals. Accordingly, lessened activity of
      monoacylglycerol and diacylglycerol acyltransferase was recorded. As assessed in
      cultured jejunal explants incubated with either [(14)C]-oleic acid or [(35)S]
      methionine, fish oil feeding resulted in diminished triglyceride-rich lipoprotein
      assembly and apolipoprotein (apo) B-48 biogenesis, respectively. The mechanisms
      did not involve apo B-48 transcription or alter the gene expression and activity
      of the critical microsomal triglyceride transfer protein. Rather, the suppressed
      production of apo B-48 by n-3 fatty acids was associated with intracellular
      proteasome-mediated posttranslational downregulation in insulin-resistant and
      diabetic animals. CONCLUSIONS/INTERPRETATION: Our data highlight the beneficial
      impact of n-3 fatty acids on adverse effects of the metabolic syndrome and
      emphasise their influence on intestinal lipid transport, an effect which may
      limit postprandial lipaemia and the risk of atherosclerosis.

PMID- 16788802
TI  - Increasing incidence of diagnosed type 2 diabetes in Taiwan: analysis of data
      from a national cohort.
AB  - AIMS/HYPOTHESIS: Epidemiological evidence shows an increasing prevalence of type
      2 diabetes in Taiwan. The aim of this study was to assess the yearly incidence
      for this country during 1992-1996. SUBJECTS AND METHODS: Data obtained by
      telephone interviews of 93,484 diagnosed diabetic patients enrolled in Taiwan's
      National Health Insurance programme formed the basis of this study. A total of
      36,153 incident cases of type 2 diabetes (17,097 men and 19,056 women) were
      identified and incidence rates calculated. The trends of obesity and parental
      diabetes were also evaluated. RESULTS: The overall 5-year incidences for men and
      women were 187.1 and 218.4 per 100,000 population, respectively. The trends from
      1992-1996 were increased for all age groups in men and for most age groups in
      women. A 2.8-fold increase in incidence was observed for the youngest age group
      (<35 years), in which the increase in incidence was higher than in the older age
      groups. Men showed a higher fold increase in incidence than did women (3.5 vs
      2.1). Obesity at interview increased from 39.2% in 1992 to 47.6% in 1996
      (p<0.001) and was significant for all ages. Parental diabetes showed no yearly
      change when all patients were analysed together, but there was a trend towards a
      decrease in the youngest age group (<35 years) and a trend towards an increase in
      the oldest age groups (>/=55 years). CONCLUSIONS/INTERPRETATION: An increasing
      incidence of diagnosed type 2 diabetes was observed for each sex in most age
      groups in Taiwan, but was most marked in the youngest age group. A parallel
      increase in obesity was observed with the increasing incidence of diabetes.

PMID- 16788803
TI  - Association of statin therapy and increased survival in patients with multiple
      organ dysfunction syndrome.
AB  - OBJECTIVE: The multiple organ dysfunction syndrome (MODS) is the sequential
      failure of several organ systems after a trigger event, such as sepsis, pneumonia
      or cardiogenic shock. Even today, mortality is high. Statin therapy is associated
      with reduction of inflammation and subsequent rates of severe sepsis and ICU
      admission of patients admitted to hospital with presumed or documented acute
      bacterial infection. Our study aimed to characterize a potential survival benefit
      by statin therapy in MODS patients. DESIGN: Retrospective cohort study. SETTING:
      Twelve-bed medical intensive care unit in a university center. PATIENTS: Forty
      score-defined MODS patients under statin treatment and 80 age- and sex-matched
      score-defined MODS patients without statin treatment. Inclusion criterion was an
      APACHE II score > or = 20 at admission to ICU. INTERVENTIONS: Assessment of
      statin treatment and calculation of disease severity by scoring. The patients
      were followed up for 28-day mortality as well as for hospital mortality.
      MEASUREMENTS AND RESULTS: The MODS severity was equally pronounced in both
      groups. There were 42/80 deaths in the group without statin treatment and 13/40
      deaths in the statin group (28-day mortality 53% vs. 33%, p = 0.03). Cox
      proportional hazard analysis revealed a hazard ratio of 0.53 (95% CI 0.29-0.99, p
      = 0.04). Hospital mortality was calculated at 72% (non-statin group) vs. 35%
      (statin group; chi-square = 15.6, p < 0.0001). The overall hospital mortality was
      60%. CONCLUSIONS: Patients under statin treatment developing MODS might have a
      better outcome than patients without statin therapy, probably by reduction of
      inflammatory responses and increase of vagal activity in MODS.

PMID- 16788805
TI  - The use of sildenafil in the therapy of massive pulmonary embolism.

PMID- 16788804
TI  - Stress ulcer prophylaxis in mechanically ventilated patients: integrating
      evidence and judgment using a decision analysis.
AB  - OBJECTIVE: Stress ulcer prophylaxis with a histamine-2 receptor antagonist can
      reduce the risk of gastrointestinal bleeding in mechanically ventilated patients
      but may also increase the risk of ventilator-associated pneumonia. We sought to
      clarify the tradeoffs involved in selecting a prophylactic strategy. DESIGN:
      Decision analysis. PATIENTS AND PARTICIPANTS: A decision tree was constructed for
      a hypothetical cohort of patients receiving mechanical ventilation for an
      expected duration of longer than 48 h, using probabilities estimated from the
      published literature. INTERVENTIONS: Patients in the model could receive either
      prophylaxis with a histamine-2 receptor antagonist or no prophylaxis. Sensitivity
      analyses were preformed varying the estimated probabilities over their plausible
      ranges. MEASUREMENTS AND RESULTS: Both strategies were associated with
      approximately the same baseline expected mortality (16.6% for histamine-2
      receptor antagonists and 16.9% for no prophylaxis, risk difference 0.3%). Varying
      the estimated probabilities resulted in only small changes in both the expected
      mortality and the absolute risk reduction associated with the preferred
      treatment. At the extremes of assumptions the absolute mortality reduction ranged
      from 0.1% to 3.3%. CONCLUSIONS: No single strategy of stress ulcer prophylaxis is
      preferred when mortality is used as the outcome. In the absence of a clinical
      trial demonstrating survival benefit the individual clinician's assumptions
      regarding the effect of prophylaxis on gastrointestinal bleeding and pneumonia
      and the attributable mortality of pneumonia vs. gastrointestinal bleeding will
      have a significant effect on the decision.

PMID- 16788806
TI  - Impact of the suctioning system (open vs. closed) on the incidence of ventilation
      associated pneumonia: Meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Ventilation-associated pneumonia (VAP) is a serious complication of
      patients in intensive care units (ICU) who require mechanical ventilation. The
      choice of suctioning system (open vs. closed) remains unresolved in evidence
      based guidelines. This meta-analysis was carried out to analyze the effect of the
      type of suctioning system on the incidence of VAP. DESIGN: A search of the
      literature was used to identify randomized controlled trials addressing this
      question. A meta-analysis was then performed to calculate the relative risk of
      ventilation-associated pneumonia acquisition with the two suctioning systems.
      RESULTS: Nine trials were included, with 648 patients in the open suctioning
      group and 644 in the closed suctioning group. VAP occurred in 128 (20%) of the
      open suctioning group and in 120 (19%) in the closed suctioning group (relative
      risk 0.95). CONCLUSIONS: At a given pneumonia prevalence of 20% in ICU patients
      there was no significant advantage for the use of either suctioning system in
      this meta-analysis. The choice of suctioning system should therefore be based on
      handling, cost, and individual patient's disease until more data are available.

PMID- 16788807
TI  - Acquisition of imipenem-resistant Acinetobacter baumannii in a pediatric
      intensive care unit: A case-control study.
AB  - OBJECTIVE: To investigate the risk factors associated with nosocomial acquisition
      of imipenem-resistant Acinetobacter baumannii (IRAB) among pediatric intensive
      care patients. A retrospective case control study was conducted in a pediatric
      intensive care unit (PICU). PATIENTS AND PARTICIPANTS: Cases were children in
      whom IRAB was isolated from any clinical specimen obtained at least 48 h
      following admission to PICU. Controls were children without IRAB matched to cases
      in 2:1 ratio. Twenty-six cases were matched with 52 controls according to the
      chronological order of admission. MEASUREMENTS AND RESULTS: Between July 2001 and
      December 2003, 52 (62%) of 84 clinical A. baumannii isolates were found
      nonsusceptible to imipenem (MIC > or = 8 microg/ml). Demographic variables,
      comorbid conditions, clinical picture at admission, invasive procedures, use of
      antimicrobials and other drugs were analyzed as potential risk factors. Use of
      carbapenems and other beta-lactams, aminoglycosides, ranitidine, mechanical
      ventilation, central venous or urinary catheters and length of stay in PICU were
      among the factors significantly associated with IRAB acquisition in the
      univariate analysis. By multivariate analysis, however, only aminoglycoside use
      and length of stay in the PICU were independent risk factors. CONCLUSIONS:
      Acquisition of IRAB by PICU patients was independently associated with
      aminoglycoside use and prolonged stay in the unit. Studies of evaluation of
      infection control policies need to be pursued.

PMID- 16788808
TI  - Early enteral immunonutrition vs. parenteral nutrition in critically ill patients
      without severe sepsis: a randomized clinical trial.
AB  - OBJECTIVES: We compared early parenteral nutrition (PN) and early enteral
      immunonutrition (iEN) in critically ill patients, distinguishing those with and
      without severe sepsis or septic shock (SS) on admission to intensive care units
      (ICUs). DESIGN AND SETTING: Multicenter, randomized, unblinded clinical trial in
      33 Italian general ICUs. PATIENTS AND PARTICIPANTS: The study included 326
      patients, 287 of whom did not have SS on ICU admission. Eligibility criteria
      excluded the two tails in the spectrum of critical conditions, i.e., patients
      either too well or too ill. Of the patients recruited 160 were randomized to iEN
      (142 without SS) and 166 to PN (145 without SS). INTERVENTIONS: Patients were
      randomized to two arms: early iEN or early PN. MEASUREMENTS AND RESULTS: Primary
      endpoint was 28-day mortality for all patients and the occurrence of SS during
      ICU stay for patients admitted without such condition. While 28-day mortality did
      not differ between iEN and PN (15.6% vs. 15.1%), patients without SS who received
      iEN had fewer episodes of severe sepsis or septic shock (4.9% vs. 13.1%). ICU
      length of stay was 4 days shorter in patients given iEN. CONCLUSIONS: Compared to
      parenteral nutrition iEN appears to be beneficial in critical patients without
      severe sepsis or septic shock. Parenteral nutrition in these patients should be
      abandoned, at least when enteral nutrition can be administered, even at an
      initial low caloric content.

PMID- 16788809
TI  - Mobilization of bone marrow-derived mesenchymal stem cells into the injured
      tissues after intraarticular injection and their contribution to tissue
      regeneration.
AB  - The purpose of present study was to evaluate active mobilization effect of
      mesenchymal stem cells (MSCs) into injured tissues after intraarticular injection
      of MSCs, and to evaluate their contribution to tissue regeneration. MSCs, which
      were obtained from green fluorescent protein (GFP) transgenic Sprague-Dawley (SD)
      rat and cultivated, were injected into normal SD rats in which multiple tissues
      had been injured including anterior cruciate ligament (ACL), medial meniscus, and
      articular cartilage of the femoral condyles. At 4 weeks after injection of MSCs,
      fluorescent microscopic observation, immunohistochemical or histological
      examinations were performed to evaluate mobilization of MSCs into injured tissue
      and their contribution to tissue regeneration. In the group of 1 x 10(6) MSCs
      injection, GFP positive cells could mobilize into the injured ACL alone in all 8
      knees. In the group of 1 x 10(7) MSCs injection, GFP positive cells were observed
      in the injured site of ACL in all 8 knees and in the injured site of medial
      meniscus and cartilage of femoral condyles in 6 of 8 knees. More interestingly,
      extracellular matrix stained by toluidine blue was present around GFP positive
      cells in the injured femoral condyles cartilage and medial meniscus, indicating
      tissue regeneration. Intraarticularly injected MSCs could mobilize into the
      injured tissues, and probably contributed to tissue regeneration. This study
      demonstrated the possibility of intraarticular injection of MSCs for the
      treatment of intraarticular tissue injuries including ACL, meniscus, or
      cartilage. If this treatment option is established, it can be minimally invasive
      compared to conventional surgeries for these tissues.

PMID- 16788810
TI  - Orientation feedback during simulated simple translation tests has little
      clinical significance on the magnitude and precision of glenohumeral joint
      translations.
AB  - The repeatability of shoulder instability clinical examinations has been reported
      to be poor, producing a large range of translations. The objective of this study
      was to determine the effect of providing the clinician with joint orientation
      feedback on the magnitude and precision of glenohumeral joint kinematics. A 6
      degree of freedom magnetic tracking system was used to determine the kinematics
      of the humerus with respect to the scapula (n=8 cadaveric shoulders). The joints
      were preconditioned with simple loading tests five times. At 60 degrees of
      glenohumeral abduction and 0 degrees of flexion/extension, a clinician then
      applied an anterior and posterior load to the humerus until a manual maximum
      simulating a simple translation test (STT) was achieved at 0, 30, and 60 degrees
      of external rotation with and without angular orientation feedback of the humerus
      with respect to the scapula. The precision for the external rotation was within
      4.3 degrees for the feedback group and 17.5 degrees for the no feedback group
      over all external rotations. For achieving the target external rotation of 30
      degrees , there was a significant difference in precision between the feedback
      and no feedback groups (p<0.05). The magnitudes of the anterior translations were
      18.2+/-5.3, 15.5+/-5.1, and 9.9+/-5.5 mm for the feedback group and 19.3+/-6.6,
      17.5+/-4.9, and 11.5+/-5.3 mm for the no feedback group, at 0, 30, and 60 degrees
      of external rotation, respectively. There was a significant difference in the
      precision of anterior translation at 30 and 60 degrees of external rotation for 4
      of 8 specimens (p<0.05). Significant differences in the precision of the
      posterior translation was only detected at 0 degrees of external rotation for 3
      of 8 specimens (p<0.05). Based on the data obtained, providing orientation
      feedback to a clinician performing a simulated STT results in increased precision
      for not only the target external rotations but also the resulting glenohumeral
      translations. While providing feedback may be a necessary step to achieving
      precise results for experimental studies, the magnitudes of translations in the
      anterior and posterior directions were relatively similar for the feedback and no
      feedback states indicating little benefit for clinical examinations.

PMID- 16788811
TI  - Factors producing a menopausal depressive-like state in mice following
      ovariectomy.
AB  - RATIONALE: Bilateral ovariectomy in female mice produces a menopausal depressive
      like state but the factors responsible for the phenomenon are unknown.
      OBJECTIVES: We elucidated methodological issues related to establishing this
      mouse model and investigated a possible mechanism underlying the depressive-like
      state of ovariectomized mice. METHODS: We removed both ovaries of female ICR mice
      at 9 weeks of age. Changes in the immobility time during the forced swimming test
      as a function of the time interval between ovariectomy and behavioral testing
      were determined on nine different days after surgery. To assess behavioral
      specificity, the elevated plus-maze (EPM) behavior and spontaneous activity were
      measured. With respect to the effect of ovariectomy on the immobility time, we
      compared ICR mice with three other strains of mice (C57BL/6J, DBA/2N, and CD-1).
      Finally, we investigated the effects of (-)-2,5-dimethoxy-4-iodoamphetamine (DOI)
      and (+/-)-8-hydroxy-2-(N,N-di-n-propylamino) tetralin (8-OH-DPAT) on the
      immobility time of ovariectomized mice. RESULTS: A significant effect on the
      prolongation of immobility was observed between 12 and 18 days after ovariectomy.
      Ovariectomy did not alter either the EPM behavior or spontaneous activity. Of the
      four strains of mice, only DBA mice did not show any significant prolongation of
      immobility after ovariectomy. Acute or chronic treatment with DOI (0.5 or 1.0 mg
      kg(-1)) significantly prevented the prolongation of immobility time, whereas
      acute and chronic treatments with 8-OH-DPAT (0.05, 0.5, or 1.0 mg kg(-1)) were
      ineffective. CONCLUSION: The present findings have potentially important
      implications for evaluating a candidate substance for the management of mood
      disorders in menopausal women.

PMID- 16788812
TI  - Implicit sequence learning without motor sequencing in young and old adults.
AB  - The ability to detect patterns and organize individual events into complex
      sequences is a fundamental cognitive skill that is often learned implicitly. The
      serial response time (SRT) task has been widely used to investigate implicit
      sequence learning, but it remains unclear whether people learn a perceptual or
      motor sequence in this task. This study reports three experiments that build on
      previous research by Goschke and colleagues using an auditory SRT task in which
      the stimulus-to-response mapping changes on every trial to eliminate spatio-motor
      sequencing. The current study extends earlier work in three ways. First, healthy
      young and older adults were tested rather than the neuropsychological patients
      used in previous research. Second, sequences of different structural complexity
      were investigated including first- and second-order repeating sequences as well
      as higher-order probabilistic sequences. Third, the potential role of explicit
      knowledge was examined using three separate tests of declarative knowledge.
      Results indicate that young and old adults are able to learn purely perceptual
      auditory sequences, but that explicit knowledge contributes to learning of
      repeating sequences by young adults.

PMID- 16788813
TI  - CT of tracheal agenesis.
AB  - BACKGROUND: Tracheal agenesis is a rare and usually lethal anomaly. In the past,
      opaque contrast medium was injected via the esophagus to demonstrate the anatomy.
      OBJECTIVE: To demonstrate the utility of helical and multidetector CT in
      delineating the aberrant anatomy in newborns with tracheal agenesis. MATERIALS
      AND METHODS: Four newborns with tracheal agenesis were identified from three
      institutions. Imaging studies and medical records were reviewed. Each child was
      imaged with chest radiography. One child was imaged on a single-detector helical
      CT scanner and the other three on multidetector scanners. RESULTS: Helical and
      multidetector CT with 2D and 3D reconstructions clearly delineated the aberrant
      tracheobronchial and esophageal anatomy in each infant. Minimum intensity
      projection reformatted CT images were particularly helpful. One infant each had
      type I and type II tracheal agenesis. Two infants had type III tracheal agenesis.
      All four infants died. CONCLUSION: CT is a useful tool for delineating the
      aberrant anatomy of newborns with tracheal agenesis and thus helps in making
      rational clinical decisions.

PMID- 16788815
TI  - Management of non-complicated BPH: proposition of a renewed decision tree.
AB  - Nowadays the management of benign prostatic hypertrophia (BPH) is undergoing
      striking changes. The standard medical treatments are represented by three
      families which are the phytotherapy, the alpha-blockers and the 5-alpha-reductase
      inhibitors. These treatments were deemed as symptomatic and used only as
      monotherapy. Recent numerous studies bring new assessments on BPH: the medical
      treatment is able to modify the natural history of BPH especially by reducing the
      risk of acute urinary retention. Furthermore the association of two different
      therapeutic classes seems to be more efficient than the use of a monotherapy in
      some cases. Similarly the place of two instrumental techniques, the thermotherapy
      by microwaves or by radiofrequencies, previously proposed as alternatives to the
      surgical treatment seems to find their way rather as alternatives to the medical
      treatment. These different elements allow building a renewed decision tree which
      decisions are shared with the patient at each stage. This decision tree of the
      management of patients having non-complicated BPH symptoms must include initial
      clinical characteristics of the patient and its disease and the evolution under
      treatment which has not been yet considered in the international recommendations.
      It also considers the possibilities of associations with other therapeutic
      classes.

PMID- 16788817
TI  - Behavioural examination of the infrared sensitivity of rattlesnakes (Crotalus
      atrox).
AB  - Pitvipers (Crotalinae) and boid snakes (Boidae) possess highly sensitive infrared
      (IR) receptors. The ability of these snakes to image IR radiation allows the
      assessment of the direction and distance of an IR source (such as warm-blooded
      prey) in the absence of visual cues. The aim of this study was to determine the
      behavioural threshold of snakes to an IR stimulus. A moving IR source of constant
      size and temperature was presented to rattlesnakes (Crotalus atrox) at various
      distances (10-160 cm) from their snout. The snakes' responses were quantified by
      measuring distinct behavioural changes during stimulus presentation (head jerks,
      head fixed, freezing, rattling and tongue-flicking). The results revealed that C.
      atrox can detect an artificial IR stimulus resembling a mouse in temperature and
      size up to a distance of 100 cm, which corresponds to a radiation density of 3.35
      x 10(-3) mW/cm2. These behavioural results reveal a 3.2 times higher sensitivity
      to IR radiation than earlier electrophysiological investigations.

PMID- 16788816
TI  - Steroid hormone activation of wandering in the isolated nervous system of Manduca
      sexta.
AB  - Steroid hormones modulate motor circuits in both vertebrates and invertebrates.
      The insect Manduca sexta, with its well-characterized developmental and
      endocrinological history, is a useful model system in which to study these
      effects. Wandering is a stage-specific locomotor behavior triggered by the
      steroid hormone 20-hydroxyecdysone (20E), consisting of crawling and burrowing
      movements as the animal searches for a pupation site. This study was undertaken
      to determine whether the wandering motor pattern is activated by direct action of
      20E on the CNS. 20E acts on the isolated larval nervous system to induce a
      fictive motor pattern showing features of crawling and burrowing. The latency of
      the response to 20E is long, suggestive of a genomic mechanism of action. The
      abdominal motoneurons or segmental pattern generating circuits are unlikely to be
      the primary targets of 20E action in inducing fictive wandering. Exposure of the
      segmental ganglia alone to hormone did not evoke fictive wandering. Therefore, as
      suggested by an earlier study, the likely site of 20E action is within the brain.

PMID- 16788818
TI  - Vitamin D and estrogen receptor gene polymorphisms and the risk of colorectal
      cancer in Bulgaria.
AB  - BACKGROUND AND AIMS: Different epidemiological studies report the protective
      effect on colorectal cancer (CRC) exerted by vitamin D(3) intake, estrogen
      replacement therapy, and increase of the risk of microsatellite instability (MSI)
      in CRC by withdrawal of estrogens. The aim of our study was to search for
      association between CRC and polymorphisms in estrogen receptor-alpha (ER-alpha)
      and Vitamin D receptor (VDR) genes. MATERIALS AND METHODS: We analyzed the PvuII
      and XbaI polymorphisms from the ER-alpha gene and the BsmI polymorphism of the
      VDR gene in 140 patients with CRC (subsequently divided according to their MSI
      status) and 94 controls. RESULTS: We have demonstrated that the presence of the
      PvuII pp genotype increased the risk of developing MSI(+) tumors about three
      times compared to MSI(-) tumors [odds ratio (OR)=3.09, 95% confidence interval
      (CI) 0.88-10.91]. The effect of the XbaI xx genotype was similar (OR=2.08, 95% CI
      0.49-8.81). Our results for the VDR BsmI polymorphism showed an increased risk
      for CRC in bb carriers (OR=1.8, 95% CI 0.81-4.05). CONCLUSION: We conclude that
      PvuII and XbaI polymorphisms in the ER-alpha gene were associated with the risk
      of developing MSI in CRC patients. The BsmI polymorphism in the VDR gene was
      linked to the risk of developing CRC.

PMID- 16788819
TI  - Anorectal necrosis induced by injection sclerotherapy for hemorrhoids.

PMID- 16788820
TI  - Optic nerve axonal pathology is related to abnormal visual evoked responses in
      AIDS.
AB  - Electrophysiological studies in subjects with HIV/AIDS demonstrate subtle changes
      in the visual pathway even in the absence of visual symptoms. But the
      pathological correlate of the electrophysiological abnormalities is largely
      unknown. This study attempts to correlate pathological changes in the retina and
      intraorbital portion of optic nerve in four drug naive patients of AIDS caused by
      HIV-1 clade C, who had abnormalities in the visual evoked potentials recorded
      antemortem. Three had no visual complaints and one patient had sudden loss of
      vision in the right eye. In all four patients, the visual evoked potentials
      disclosed variable prolongation of P100 latencies. Histologically axonal
      cytoskeletal breakdown and depletion in the optic nerves was the cardinal finding
      with variable myelin loss, even in the absence of overt visual dysfunction, or
      infective retinitis. The axonal loss was maximal in the symptomatic case. Retinal
      ganglion cell depletion was seen in only two patients. Sectoral infiltration of
      the optic nerve by cryptococci and Cryptococcal choroiditis was the only
      opportunistic infection to involve the eye. Axonal pathology in the optic nerve
      appears to be related to the abnormalities recorded in visual evoked potentials
      even in the absence of overt clinical symptoms. Opportunistic infections could be
      contributing to the axonal pathology in the optic nerve in patients with AIDS.

PMID- 16788821
TI  - Effect of 6-hydroxydopamine treatment on kynurenine aminotransferase-I (KAT-I)
      immunoreactivity of neurons and glial cells in the rat substantia nigra.
AB  - Parkinson's disease (PD), a progressive neurodegenerative disorder, is
      characterized by a preferential loss of dopaminergic neurons in the substantia
      nigra pars compacta (SNPC). Neurons in the SNPC are known to express tyrosine
      hydroxylase (TH); therefore, in a commonly used PD model, 6-hydroxydopamine (6
      OHDA), a selective catecholamine neurotoxin, induces neuronal death in SNPC. We
      have shown with immunohistochemical techniques that kynurenine aminotransferase-I
      (KAT-I), the enzyme taking part in the formation of kynurenic acid (KYNA)--the
      only known endogenous selective NMDA receptor antagonist and a potent
      neuroprotective agent--is also expressed in the rat SNPC. We found that KAT-I and
      TH co-exist in the very same neurons of SNPC and that 6-OHDA injected into the
      lateral ventricle produced loss of the majority of nigral neurons. Densitometric
      analysis proved that, in consequence of 6-OHDA treatment, not only TH but also
      KAT-I immunoreactivity diminished considerably in the remaining SNPC neurons.
      Astrocytes in the substantia nigra were found to express KAT-I under normal
      conditions; the amount of this enzyme increased after administration of 6-OHDA,
      whereas microglial cells became KAT-I immunoreactive only after 6-OHDA treatment.
      Since intrinsic KYNA in SNPC neurons is perceptibly insufficient to protect them
      from the deleterious effect of 6-OHDA, it is hypothesized that biochemical
      approaches which increase KYNA content of the central nervous system might
      prevent the deleterious effect of 6-OHDA and, supposedly, also the neuronal
      degradation characterizing PD.

PMID- 16788822
TI  - Rimmed vacuoles with beta-amyloid and tau protein deposits in the muscle of
      children with hereditary myopathy.
AB  - We investigated whether beta-amyloid and tau protein are involved in the
      formation of inclusion body myositis (IBM)-like inclusions found in children with
      rimmed vacuoles and congenitally affected muscles. We immunostained muscle biopsy
      specimens from four children and one 18-year-old boy with congenital myopathy
      containing rimmed vacuoles and IBM-like inclusions with antibodies against beta
      amyloid, tau protein and ubiquitin. Focal accumulations of both beta-amyloid and
      phosphorylated tau coexisted with tubulofilamentous structures in all cases. Our
      studies demonstrate for the first time that the full morphological phenotype of
      IBM including beta-amyloid and tau protein deposits may also develop in children,
      and that congenital, probably genetic, muscle defects may lead to abnormal
      protein aggregation in IBM-like inclusions.

PMID- 16788823
TI  - Sequence homogenization and chromosomal localization of VicTR-B satellites differ
      between closely related Vicia species.
AB  - Satellite sequences of the VicTR-B family are specific for the genus Vicia
      (Leguminosae), but their abundance varies among the species, being the highest in
      Vicia sativa and Vicia grandiflora. In this study, we have sequenced multiple
      randomly cloned VicTR-B fragments from these two species and analyzed their
      sequence variability, periodicity, and chromosomal localization. We have found
      that V. sativa VicTR-B sequences are homogeneous with respect to their nucleotide
      sequences and periodicity (monomers of 38 bp), whereas V. grandiflora repeats are
      considerably more variable, occurring in at least four distinct sequence
      subfamilies. Although the periodicity of 38 bp was conserved in most of the V.
      grandiflora sequences, one of the subfamilies was composed of higher-order
      repeats of 186 bp, which originated from a pentamer of the basic repeated unit.
      Individual VicTR-B subfamilies were preferentially located in either intercalary
      or subtelomeric regions of chromosomes. Interestingly, two V. grandiflora
      subfamilies with the highest similarity to V. sativa VicTR-B sequences were
      located in intercalary heterochromatic bands, showing similar chromosomal
      distribution as the majority of VicTR-B repeats in V. sativa. The other two V.
      grandiflora subfamilies showing a considerable divergence from V. sativa
      sequences were found to be accumulated at subtelomeric regions of V. grandiflora
      chromosomes.

PMID- 16788824
TI  - Modelling the normal retinal nerve fibre layer thickness as measured by Stratus
      optical coherence tomography.
AB  - BACKGROUND: The variation in retinal nerve fibre layer thickness (RNFLT) as
      measured by Stratus optical coherence tomography (OCT) in healthy subjects may be
      reduced when the effect on RNFLT measurements of factors other than disease is
      corrected for, and this may improve the diagnostic accuracy in glaucoma. With
      this perspective we evaluated the isolated and combined effects of factors
      potentially affecting the Stratus OCT RNFLT measurements in healthy subjects.
      METHODS: We included 178 healthy eyes of 178 subjects between 20 and 80 years of
      age. Participants underwent an extensive eye examination. Stratus OCT RNFLT was
      measured by three standard protocols, two with high and one with standard image
      resolution. Effects on RNFLT of age, gender, refractive error, axial length, lens
      nuclear colour and opalescence, intra-ocular pressure (IOP), and optic disc size
      were examined by univariate and multivariate analyses. RESULTS: Age, refractive
      error, axial length, and lens nuclear colour and opalescence affected RNFLT in
      univariate analyses, whereas gender, IOP, and optic disc size had no significant
      effect. In multivariate analyses only age in combination with refractive error,
      or with axial length, was significant and explained 14.7-17.6% (R2) of the total
      variation of RNFLT, approximately 50% more than age alone. RNFLT decreased by 2.6
      2.9 microm per increasing decade of age and increased by 1.5-1.8 microm per more
      positive diopter of spherical equivalent using full-circle measurements of the
      three standard protocols. These effects varied between measurement sectors.
      CONCLUSIONS: RNFLT as measured by Stratus OCT standard protocols was
      significantly affected by age and refractive status. The effect on global RNFLT
      of a difference in refractive error of 10 diopters corresponded to the effect of
      a difference in age of 60 years. Theoretically, the effect of refractive status
      may be explained by artefacts of RNFLT measurement circle placement. The results
      suggest that the diagnostic accuracy of Stratus OCT may be improved by
      considering refractive status in addition to age when RNFLT is measured. For this
      purpose spherical equivalent seems as effective as axial length.

PMID- 16788825
TI  - Multifocal posterior uveitis in Crohn's disease.
AB  - PURPOSE: To report a case of rare posterior eye manifestation of Crohn's disease
      preceding recurrence of inflammatory bowel disease. METHODS: Case report with
      ophthalmoscopic findings, fluorescein/indocyanin green angiograms, automated
      perimetry and multifocal-ERG. RESULTS: The perimetry revealed absolute and
      relative scotomas corresponding to multifocal inflammatory lesions in the retina
      and choroid, reduced a/b amplitudes in multifocal-ERG and hypofluorescent dots in
      angiography. Under oral prednisolone visual defects, ophthalmoscopic and
      angiographic findings resolved, while a/b amplitudes remained mildly reduced. The
      ocular changes occurred without systemic hypertension and were followed by a new
      episode of intestinal symptoms. CONCLUSION: Multifocal inflammatory lesions in
      the retina and choroid in patients with Crohn's disease may occur and may precede
      a recurrent intestinal episode. Crohn's patients should be carefully followed up
      in collaboration with internal medicine specialists.

PMID- 16788826
TI  - Outcomes of surgery for posterior segment intraocular foreign bodies--a
      retrospective review of 17 years of clinical experience.
AB  - BACKGROUND: To determine the outcome of surgery in patients who presented with
      posterior segment intraocular foreign bodies (IOFBs) and to identify factors
      associated with poor visual outcome. To assess whether improvement in vitreo
      retinal surgical techniques over the past 17 years has resulted in an improvement
      in the outcome of these patients. METHODS: A retrospective cohort study carried
      out at Moorfields Eye Hospital, London. Patients who underwent a primary surgical
      repair and removal of a posterior segment IOFB were identified using a hospital
      database. Of the 140 patients identified, 114 (81%) were included in the study.
      Data on age, activity at time of injury, presenting clinical features, surgical
      techniques, complications and final visual outcome were recorded and analyzed.
      RESULTS: The mean age at time of injury was 34.6+/-12.4 years. All patients were
      male. The majority of IOFBs were metal (83%). Hammering and chiselling were the
      most common activities at the time of injury (66%). Fifty-three percent of
      patients presented with a visual acuity of 6/ 36 or better. Primary closure was
      achieved in a median of 1 day (interquartile range 1-3 days) following injury. A
      final visual outcome of 6/60 or worse was documented in 31%. Presentation with a
      relative afferent pupillary defect (P<0.001), hyphaema (P=0.024), vitreous
      haemorrhage (P=0.003), uveal prolapse (P=0.038) or retinal detachment (P=0.031)
      was associated with a poor visual outcome (6/60 or worse). Postoperative
      complications of retinal detachment (P<0.001) and proliferative vitreoretinopathy
      (P<0.001) were prognostic of poor final visual acuity. Improvements in surgical
      techniques, e.g. panoramic viewing systems has resulted in a significant
      improvement in the final visual outcome of these patients (P=0.043). CONCLUSION:
      This large series of posterior segment IOFBs shows that recent advances in
      surgical techniques are associated with a significant improvement in prognosis.

PMID- 16788828
TI  - Diagnosis of primary esophageal synovial sarcoma by demonstration of t(X;18)
      translocation: a case report.
AB  - Synovial sarcoma (SS) is an uncommon soft tissue tumor occurring mainly in the
      periarticular region of the extremities of young adults. In this report, we
      describe a very rare occurrence of primary SS of the esophagus in a 72-year-old
      woman. Histologically, the tumor demonstrated biphasic morphologic findings
      associated with poorly differentiated areas. Tumor cells expressed vimentin,
      epithelial (EMA, CK7, AE1/3), bcl-2 and neuroectodermal (CD56, CD57, CD99)
      antigens. Differential diagnose included esophageal sarcomatoid carcinoma.
      Cytogenetic analysis confirmed the diagnosis of SS by identifying t(X;18)
      translocation. The literature of this very uncommon entity of the esophagus is
      reviewed.

PMID- 16788830
TI  - Naphazoline intoxication in children.

PMID- 16788829
TI  - Safe and unsafe duration of fasting for children with MCAD deficiency.
AB  - OBJECTIVE: To study the safe and unsafe duration of fasting in children with
      medium chain acyl-Coenzyme A dehydrogenase (MCAD) deficiency, the literature and
      the database on Dutch MCAD-deficient patients were searched for data on fasting
      studies in patients with MCAD deficiency. MATERIALS AND METHODS: These data were
      extended with information on fasting studies performed on our patients with MCAD
      deficiency known in the Beatrix Children's Hospital, UMC Groningen, The
      Netherlands. The data reflect considerable inter-individual variation and overlap
      between safe and unsafe duration of fasting. RESULTS: In six out of 35 fasting
      tests, symptoms were reported before hypoglycaemia was observed. Until 1 year of
      age, the median safe and unsafe duration of fasting was 12 hours (n=7, range 8-19
      hours) and 18 hours (n=5, range 15-20 hours), respectively. After the first year
      of life, the median safe and unsafe duration of fasting was 18 hours (n=17, range
      10-24 hours) and 20 hours (n=9, range 13-32 hours), respectively. CONCLUSION:
      Therefore, to conclude, we recommend a maximum duration of fasting in children
      with MCAD deficiency of 8 hours between 6 months and 1 year of age, 10 hours in
      the second year of life and 12 hours thereafter. From this study, no conclusions
      can be drawn on the duration of fasting during situations of intercurrent
      illness, especially with fever.

PMID- 16788831
TI  - Mitochondrial cytochrome c oxidase subunit 1 gene and nuclear rDNA regions of
      Enterobius vermicularis parasitic in captive chimpanzees with special reference
      to its relationship with pinworms in humans.
AB  - Sequences of mitochondrial cytochrome c oxidase subunit 1 (CO1) gene, nuclear
      internal transcribed spacer 2 (ITS2) region of ribosomal DNA (rDNA), and 5S rDNA
      of Enterobius vermicularis from captive chimpanzees in five zoos/institutions in
      Japan were analyzed and compared with those of pinworm eggs from humans in Japan.
      Three major types of variants appearing in both CO1 and ITS2 sequences, but
      showing no apparent connection, were observed among materials collected from the
      chimpanzees. Each one of them was also observed in pinworms in humans. Sequences
      of 5S rDNA were identical in the materials from chimpanzees and humans.
      Phylogenetic analysis of CO1 gene revealed three clusters with high bootstrap
      value, suggesting considerable divergence, presumably correlated with human
      evolution, has occurred in the human pinworms. The synonymy of E. gregorii with
      E. vermicularis is supported by the molecular evidence.

PMID- 16788832
TI  - Interaction of Plasmodium falciparum histidine-rich protein II with human
      lymphocytes leads to suppression of proliferation, IFN-gamma release, and CD69
      expression.
AB  - The presence of histidine-rich protein II (HRP II) synthesized by Plasmodium
      falciparum in the plasma of malaria patients for longer periods even after
      parasite clearance raises questions about its extracellular functions. The
      present study was carried out to examine its influence on host immune system.
      Recombinant HRP-II protein was radiolabeled with (125)I to study the specific
      binding with T and B cells. We found that the binding of (125)I-HRP II with human
      T and B cells was specific, concentration dependent, saturable, and reversible.
      Scatchard plot analysis revealed two classes of binding sites for both T and B
      cells. For the T cells, the high affinity class had dissociation constant (K(d))
      of 5.61x10(-11)M, and the low affinity class had a K(d) of 8.58x10(-11) M. For
      the B cells, the high and low affinity classes had a K(d) of 1.32x10(-11) and
      2.84x10(-11) M, respectively. Dot-blot, autoradiography, and Western blot
      analysis also confirmed the specific binding of HRP II with lymphocytes. HRP II
      significantly inhibited (approximately 75%) T-cell rosette formation with sheep
      erythrocytes. HRP II also suppressed proliferation of T and B cells triggered by
      CD3 and LPS, respectively. We found a reduction in IFN-gamma release in T cells
      preincubated with HRP II. HRP II also reduced the CD69 expression on the T cells.
      In conclusion, HRP-II binding to human lymphocytes leads to suppression of some
      of their functions.

PMID- 16788833
TI  - Purification and in vitro characterization of adult canine olfactory ensheathing
      cells.
AB  - Olfactory ensheathing cells (OECs) are known to promote neural repair under
      experimental conditions. The experimental focus has so far been almost entirely
      on rodent OECs (rOECs), and hence whether human OECs (humOECs) display similar
      properties is unclear. Studies on larger mammals as an "intermediate" model may
      be helpful for translating the experimental evidence gathered so far into novel
      therapeutic strategies. In the present study, we purified adult canine OECs
      (caOECs) from the olfactory bulb and analyzed their in vitro properties with
      respect to antigen expression, proliferation, and differentiation. Secondary
      caOECs shared the expression of marker molecules and the reactivity toward growth
      factors, with rOECs and humOECs. CaOECs were positively immunostained for the low
      affinity neurotrophin receptor p75, GFAP, and O4 and proliferated in response to
      fibroblast growth factor-2 and heregulin-1beta. No decline in proliferation was
      noted at higher passages (>8). The effects of forskolin, which neither increased
      proliferation nor stimulated the expression of O4, were clearly different from
      those on rOECs. Moreover, caOECs displayed their typical spindle-shaped
      morphology only upon growth factor/forskolin addition, whereas mitotically
      quiescent caOECs had a flattened morphology. Thus, caOECs can readily be purified
      from adult canine olfactory bulb and expanded by using established OEC mitogens.
      The behavior of caOECs toward forskolin suggests that caOECs and humOECs share a
      number of properties amd implies the presence of common intracellular signalling
      pathways. CaOECs therefore represent a suitable model system relevant for humOECs
      in neural repair studies.

PMID- 16788834
TI  - Continuous delivery of a monoclonal antibody against Reissner's fiber into CSF
      reveals CSF-soluble material immunorelated to the subcommissural organ in early
      chick embryos.
AB  - The subcommissural organ (SCO) is an ependymal differentiation located in the
      dorsal midline of the caudal diencephalon under the posterior commissure. SCO
      cells synthesize and release glycoproteins into the cerebrospinal fluid (CSF)
      forming a threadlike structure known as Reissner's fiber (RF), which runs
      caudally along the ventricular cavities and the central canal of the spinal cord.
      Numerous monoclonal antibodies have been raised against bovine RF and the
      secretory material of the SCO. For this study, we selected the 4F7 monoclonal
      antibody based on its cross-reactivity with chick embryo SCO glycoproteins in
      vivo. E4 chick embryos were injected with 4F7 hybridoma cells or with the
      purified monoclonal antibody into the ventricular cavity of the optic tectum. The
      hybridoma cells survived, synthesized and released antibody into the CSF for at
      least 13 days after the injection. E5 embryos injected with 4F7 antibody
      displayed precipitates in the CSF comprising both the monoclonal antibody and
      anti-RF-positive material. Such aggregates were never observed in control embryos
      injected with other monoclonal antibodies used as controls. Western blot analysis
      of CSF from E4-E6 embryos revealed several immunoreactive bands to anti-RF (AFRU)
      antibody. We also found AFRU-positive material bound to the apical surface of the
      choroid plexus primordia in E5 embryos. These and other ultrastructural evidence
      suggest the existence of soluble SCO-related molecules in the CSF of early chick
      embryos.

PMID- 16788835
TI  - Comparison of cellular response in bovine intervertebral disc cells and articular
      chondrocytes: effects .of lipopolysaccharide on proteoglycan metabolism.
AB  - Lipopolysaccharide (LPS) induces matrix degradation and markedly stimulates the
      production of several cytokines, i.e., interleukin-1beta, -6, and -10, by disc
      cells and chondrocytes. We performed a series of experiments to compare cellular
      responses of cells from the bovine intervertebral disc (nucleus pulposus and
      annulus fibrosus) and from bovine articular cartilage to LPS. Alginate beads
      containing cells isolated from bovine intervertebral discs and articular
      cartilage were cultured with or without LPS in the presence of 10% fetal bovine
      serum. The DNA content and the rate of proteoglycan synthesis and degradation
      were determined. In articular chondrocytes, LPS strongly suppressed cell
      proliferation and proteoglycan synthesis in a dose-dependent manner and
      stimulated proteoglycan degradation. Compared with articular chondrocytes,
      nucleus pulposus cells responded in a similar, although less pronounced manner.
      However, treatment of annulus fibrosus cells with LPS showed no significant
      effects on proteoglycan synthesis or degradation. A slight, but statistically
      significant, inhibition of cell proliferation was observed at high concentrations
      of LPS in annulus fibrosus cells. Thus, LPS suppressed proteoglycan synthesis and
      stimulated proteoglycan degradation by articular chondrocytes and nucleus
      pulposus cells. The effects of LPS on annulus fibrosus cells were minor compared
      with those on the other two cell types. The dissimilar effects of LPS on the
      various cell types suggest metabolic differences between these cells and may
      further indicate a divergence in pathways of LPS signaling and a differential
      sensitivity to exogenous stimuli such as LPS.

PMID- 16788836
TI  - Neuromuscular synapses on the dactyl opener muscle of the lobster Homarus
      americanus.
AB  - The crustacean dactyl opener neuromuscular system has been studied extensively as
      a model system that exhibits several forms of synaptic plasticity. We report the
      ultrastructural features of the synapses on dactyl opener of the lobster (Homarus
      americanus) as determined by examination of serial thin sections. Several
      innervation sites supplied by an inhibitory motoneuron have been observed without
      nearby excitatory innervation, indicating that excitatory and inhibitory inputs
      to the muscle are not always closely matched. The ultrastructural features of the
      lobster synapses are generally similar to those described previously for the
      homologous crayfish muscle, with one major distinction: few dense bars are seen
      at the presynaptic membranes of these lobster synapses. The majority of the
      lobster neuromuscular synapses lack dense bars altogether, and the mean number of
      dense bars per synapse is relatively low. In view of the finding that the
      physiology of the lobster dactyl opener synapses is similar to that reported for
      crayfish, these ultrastructural observations suggest that the structural
      complexity of the synapses may not be a critical factor determining synaptic
      plasticity.

PMID- 16788837
TI  - Factors affecting outdoor exposure in winter: population-based study.
AB  - The extent of outdoor exposure during winter and factors affecting it were
      examined in a cross-sectional population study in Finland. Men and women aged 25
      74 years from the National FINRISK 2002 sub-study (n=6,591) were queried about
      their average weekly occupational, leisure-time and total cold exposure during
      the past winter. The effects of gender, age, area of residence, occupation,
      ambient temperature, self-rated health, physical activity and education on cold
      exposure were analysed. The self-reported median total cold exposure time was 7
      h/week (8 h men, 6 h women),<1 h/week (2 h men, 0 h women) at work, 4 h/week (5 h
      men, 4 h women) during leisure time and 1 h/week (1 h men, 1.5 h women) while
      commuting to work. Factors associated with increased occupational cold exposure
      among men were: being employed in agriculture, forestry and
      industry/mining/construction or related occupations, being less educated and
      being aged 55-64 years. Factors associated with increased leisure-time cold
      exposure among men were: employment in industry/mining/construction or related
      occupations, being a pensioner or unemployed, reporting at least average health,
      being physically active and having college or vocational education. Among women,
      being a housewife, pensioner or unemployed and engaged in physical activity
      increased leisure-time cold exposure, and young women were more exposed than
      older ones. Self-rated health was positively associated with leisure time cold
      exposure in men and only to a minor extent in women. In conclusion, the subjects
      reported spending 4% of their total time under cold exposure, most of it (71%)
      during leisure time. Both occupational and leisure-time cold exposure is greater
      among men than women.

PMID- 16788838
TI  - ["Don't smoke"--a confirmed factor in the primary prevention of rheumatoid
      arthritis].

PMID- 16788839
TI  - [Scleroderma associated autoantibodies - clinical and diagnostic relevance].
AB  - In systemic sclerosis (SSc) and its variants, autoantibodies are the best known
      immunological aberration. In more than 95% of the patients, antinuclear
      antibodies or other autoantibodies can be detected. In about 90% of SSc patients
      with antinuclear antibodies, scleroderma associated autoantibodies highly
      specific for systemic sclerosis are found. These autoantibodies usually exclude
      each other in individual patients, and they are detectable early, persisting
      during the course of the disease. SSc patients characterized by scleroderma
      associated autoantibodies belong to disease subsets which are relatively
      homogeneous in clinical, genetic and prognostic terms. Besides these
      diagnostically relevant autoantibodies, numerous additional ones have also been
      described. These are neither SSc specific nor mutually exclusive, and their
      antigens have only been partially characterized. Some, however, are thought to be
      relevant to the as yet unanswered question of whether autoantibodies are directly
      involved in SSc pathogenesis.

PMID- 16788840
TI  - The cost of chemotherapy-induced nausea and vomiting in Italy.
AB  - GOALS OF WORK: The aim of this paper is to analyze the costs of chemotherapy
      induced nausea and vomiting (CINV) in Italy. MATERIALS AND METHODS: In this
      prospective observational study at seven public oncology centers, incidence and
      intensity of CINV daily for 8 days after chemotherapy in consecutive patients
      receiving cisplatin-containing chemotherapy were recorded. All costs related to
      CINV (direct medical, direct nonmedical, and indirect) were recorded (in 2003
      euros). MAIN RESULTS: A total of 172 patients were enrolled; cost data were
      available for 168 patients. Thirty-seven percent of patients experienced acute
      CINV, and 57% experienced delayed CINV; 39% achieved total control, defined as no
      nausea, vomiting, or rescue therapy. Mean per-patient costs of acute and delayed
      CINV were 30.03 euro from the hospital perspective, 4.9 euro from the patient
      perspective, and 26.85 euro from the National Health Service (NHS) perspective.
      Costs of CINV were highly variable among oncology centers, largely because of
      differences in procedures for preventing delayed CINV. These costs were four
      times higher when antiemetic drugs were prescribed and paid for by the NHS than
      when antiemetic prophylaxis was provided directly from hospital pharmacies.
      Moreover, in the delayed phase, the NHS incurred a 94% increase in costs for
      patients without total control. Overall costs for patients who did not experience
      total control of CINV were 35.57 euro higher than for those who did (85%
      increase). CONCLUSIONS: Costs of CINV for the Italian NHS could be reduced if
      hospitals furnished antiemetic prophylaxis directly to patients. Better control
      of both acute and delayed CINV would improve patient well-being as well as reduce
      the budgetary impact of CINV in Italy.

PMID- 16788844
TI  - Culture of human cervical cancer cells, SiHa, in the presence of fibronectin
      activates MMP-2.
AB  - PURPOSE: Several studies indicate that integrin receptors are involved in the
      regulation of matrix metalloproteinase (MMP) expression. Integrin-ECM ligand
      interaction leads to phosphorylation of focal adhesion kinase (FAK) and
      activation of mitogen activated protein kinase pathways. In this present
      communication, we cultured human cervical cancer cells, SiHa, in the presence of
      fibronectin to study fibronectin-integrin mediated modulation of MMP activity.
      METHODS: SiHa cells were cultured in serum-free medium (SFCM) in the presence of
      fibronectin, SFCM was collected and gelatin zymography was performed. Western
      blot, RT-PCR and immunocytochemistry were performed with SiHa cells cultured in
      the presence of fibronectin. RESULTS: The culture of SiHa cells in the presence
      of 50 microg/1.5 ml fibronectin led to expression of pro-MMP-9 and activation of
      MMP-2 within 2 h. When cells were treated with ERK inhibitor (PD98059) and grown
      in the presence of fibronectin MMP-2 activation was partially inhibited, but when
      cells were treated with PI-3K inhibitor (LY294002) and grown in the presence of
      fibronectin MMP-2 activation was appreciably reduced. Tyrosine phosphorylation of
      FAK, PI-3K and ERK and nuclear trafficking of ERK were increased in SiHa cells
      grown in the presence of fibronectin. Increased MT1-MMP mRNA expression and
      processing of MT1-MMP were also observed in SiHa cells grown in the presence of
      fibronectin. CONCLUSIONS: Our findings indicate that the culture of SiHa cells in
      SFCM in the presence of fibronectin perhaps generates a signalling cascade which
      leads to the expression of pro-MMP-9 and the activation of MMP-2 within 2 h. The
      signalling pathways activated seem to be the FAK/ERK/PI-3K pathway.

PMID- 16788845
TI  - Serum CYFRA 21-1 level reflects hepatocellular carcinoma metastasis: study in
      nude mice model and clinical patients.
AB  - Our previous proteomics study on human hepatocellular carcinoma (HCC) cell
      strains revealed that cytokeratin 19 (CK19) was expressed in cells with high
      metastasis potential; we further studied serum CK19 fragment CYFRA 21-1 level in
      HCC patients and nude mice model of HCC metastasis. HCC cell line HCCLM3 was
      injected subcutaneously into 30 nude mice which were then randomized into 6
      groups of 5 mice each. The murine serum CYFRA 21-1 and pulmonary metastases were
      determined 2, 3, 4, 5, 6, and 7 weeks after injection. Serum CYFRA 21-1 levels of
      101 normal controls and 108 HCC patients were also determined. In nude mice
      model, CYFRA 21-1 level increased significantly when pulmonary metastases
      occurred. Among 108 HCC patients, 24 (22.2%) had increased serum CYFRA 21-1
      level. The presence of portal vein tumor emboli was significantly higher in CYFRA
      21-1 increased cases (33.3%, 6/24) than in CYFRA 21-1 normal cases (6.0%, 5/84)
      (x2=7.403, P < 0.01). In addition, the percentage of TNM stage III/IV tumor was
      significantly higher in CYFRA 21-1 increased patients (54.2%, 13/24) than in
      CYFRA 21-1 normal cases (21.4%, 18/84) (x2=9.776, P < 0.005). These results
      suggest that CK19 may play an important role in HCC metastasis.

PMID- 16788843
TI  - The effects of short-chain fatty acids on colon epithelial proliferation and
      survival depend on the cellular phenotype.
AB  - PURPOSE: The short-chain fatty acids (SCFA) are produced via anaerobic bacterial
      fermentation of dietary fiber within the colonic lumen. Among them, butyrate is
      thought to protect against colon carcinogenesis. However, few studies analyze the
      effects of butyrate, and other SCFA, on normal epithelial cells and on epithelial
      regeneration during disease recovery. Since there are controversial in vitro
      studies, we have explored the effects of SCFA on different biological processes.
      METHODS: We used both tumoral (HT-29) and normal (FHC) epithelial cells at
      different phenotypic states. In addition, we analyzed the in vivo activity of
      soluble dietary fiber and SCFA production in the proliferation rate and
      regeneration of intestinal epithelial cells. RESULTS: The effect of butyrate on
      epithelial cells depends on the phenotypic cellular state. Thus, in
      nondifferentiated, high proliferative adenocarcinoma cells, butyrate
      significantly inhibited proliferation while increased differentiation and
      apoptosis, whereas other SCFA studied did not. However, in normal cells or in
      differentiated cultures as well as in in vivo studies, the normal proliferation
      and regeneration of damaged epithelium is not affected by butyrate or SCFA
      exposure. CONCLUSION: Although butyrate could exert antiproliferative effects in
      tumor progression, its production is safe and without consequences for the normal
      epithelium growth.

PMID- 16788846
TI  - Role of glutathione-S-transferase and codon 72 of P53 genotypes in epithelial
      ovarian cancer patients.
AB  - PURPOSE: A series of polymorphisms in germ-line DNA have been investigated in an
      effort to delineate polygenic models of cancer susceptibility and prognosis. As
      low-penetrance susceptibility genes may combine additively or multiplicatively
      and contribute to cancer incidence and to the response to chemotherapy, we
      studied GSTT1, GSTM1, GSTO2, GSTP1 and codon 72 of p53 genotype profiles in
      ovarian cancer patients. METHODS: We compared 69 ovarian cancer patients with 222
      control healthy women paired for ethnic and life-style characteristics. Outcome
      was evaluated in 29 stage III and IV patients submitted to a platinum-based
      chemotherapy followed-up for 6-29 months (17 +/- 9 months). RESULTS: GSTT1,
      GSTM1, GSTO2 and GSTP1 genes presented a similar genotype distribution, but codon
      72 of p53 gene wild-type variant was less frequent in ovarian cancer patients
      than in controls (chi(2); P = 0.0004). CONCLUSIONS: We were unable to demonstrate
      any association between the GST genotypes studied and the risk of ovarian cancer
      but the inheritance of a heterozygous Arg/Pro genotype of p53 increased the risk
      of ovarian cancer more than 2.5 times (OR = 2.571; 95% CI = 1.453-4.550). There
      was no association of the studied genes to any clinical or pathological feature
      of the patients or to their response to chemotherapy.

PMID- 16788847
TI  - Incidence of multiple primary malignancies among patients with bone cancers in
      Sweden.
AB  - PURPOSE: The present study aimed at quantifying risks for second malignancies in
      patients with bone cancers, and risks for second bone cancers after other primary
      tumors. METHODS: Adjusted standardized incidence ratios (SIRs) were used as a
      measure of risk. RESULTS: Among 2,546 primary bone cancer patients, a total of
      171-second malignancies occurred. Besides second bone cancers, other cancer sites
      with an increased SIR were the soft tissues and endocrine glands. The overall
      risk of second malignancies following Ewing's sarcoma was 5.63, followed by
      chordoma (1.99), osteosarcoma (1.54), and chondrosarcoma (1.51). Patients
      diagnosed before age 20 years showed an increased SIR of 3.11. The increased
      occurrence of second bone cancers was noted after the cancer sites of upper
      aerodigestive tract, kidney and nervous system. CONCLUSIONS: The incidence of
      second primary malignancies in bone cancer patients was moderately increased.
      Among histological types, Ewing's sarcoma showed the highest risk of developing
      second cancers. Young age was also associated with an increased risk. Besides
      therapeutic effects, the observed excesses of a second bone or soft tissue tumor
      may be related to Li-Fraumeni syndrome. Increases at other sites may be related
      to unknown factors or spurious findings.

PMID- 16788848
TI  - Differential expression of tenascin-C splicing domains in urothelial carcinomas
      of the urinary bladder.
AB  - PURPOSE: Through alternative splicing of the extracellular matrix protein
      tenascin-C (Tn-C) primary transcript nine type III homology repeats can be
      independently included or omitted. Large, low spliced Tn-C variants (Tn-C(L)) are
      preferentially expressed during tissue remodelling processes like tumour invasion
      to modulate cell migration. The study was aimed to evaluate the differential
      expression of Tn-C splicing domains in urinary bladder carcinoma with respect to
      the invasive behaviour. METHODS: The deposition and synthesis of the Tn-C
      splicing domains A1-D was analysed in 34 urinary bladder carcinomas by
      semiquantitative immunohistochemistry using domain specific antibodies and by RT
      PCR. Results were correlated to tumour stage and grade. RESULTS: There is a
      significant increase of Tn-C(L) with higher tumour stage and grade.
      Immunohistochemistry revealed a more restricted distribution pattern of A1, B,
      and/or D domain containing Tn-C variants to invasive tumours, tumour vessels, and
      to destructed muscle. The mRNA expression patterns of the domains A1-A3 are
      similar among the different carcinomas. Stronger differences exist in the region
      from the B to D domain. In general, the domains AD1/C are rarely expressed. AD1
      domain expression seems to be connected with compact invasion pattern.
      CONCLUSION: In urinary bladder carcinoma a differential expression of Tn-C
      splicing variants exists in dependence of tumour type, vascularization, and
      invasive behaviour. Therefore, the detection of different Tn-C splicing domains
      could be useful for assessment of muscle invasion, tumour surveillance, as well
      as target structures for antibody based tumour detection and therapy.

PMID- 16788849
TI  - Prevalence of anorectal dysfunction in women attending health care services.
AB  - The aim of this study was to assess the prevalence of different bowel symptoms
      (constipation, faecal incontinence and faecal evacuation dysfunction) and
      associated urinary symptoms in women attending health care services. All women
      attending colposcopy clinics and general gynaecology clinics in a district
      general hospital in the southwest of England were invited to participate in the
      study. In addition, women attending the local family planning clinic were also
      recruited. Women attending these clinics routinely completed a history sheet and
      were asked to complete the Birmingham Bowel and Urinary Symptoms Questionnaire.
      Two hundred women participated in the study: 116 (64.4%) had at least one bowel
      symptom from the list in the questionnaire and 57 (31.6%) of women thought they
      had a bowel problem but only 26 (14.4%) consulted their family doctor regarding
      the problem while four (2.2%) were referred for specialist opinion. Six were
      unsure about their bowel symptoms. There were 46 (25.5%) of women who had
      constipation, 99 (55%) had faecal incontinence and 97 (53.8%) complained of
      faecal evacuation dysfunction. Only 48 (26.6%) of women were free of any bowel
      complaint. One patient with faecal incontinence discussed her problem with her
      midwife but no further action was taken as she was too embarrassed to discuss it
      with her doctor. Seventy-eight (43.3%) of patients had urinary symptoms. Fifty
      five (30.5%) thought they had a urinary problem but only 29 (16.1%) consulted
      their doctor and 17 (9.4%) were referred for specialist opinion. Sixty-one
      (33.8%) of those who admitted to have urinary incontinence also had faecal
      incontinence. Forty-nine (27.2%) of the patients were free of all symptoms. The
      mode of delivery as well as previous surgery did not have any influence on
      urinary incontinence nor on anal incontinence. This study has demonstrated a high
      prevalence of bowel symptoms in women attending health care services.

PMID- 16788850
TI  - Pregnancy and delivery following tension-free vaginal tape.
AB  - The tension-free vaginal tape (TVT) has become an increasingly popular, minimally
      invasive surgical treatment for urodynamic stress incontinence. As a consequence
      of its popularity, more women of childbearing age are undergoing surgery, and
      thus the incidence of pregnancy following surgery is likely to increase. We
      report two cases of unplanned pregnancy following TVT, both of which remained
      continent following delivery.

PMID- 16788851
TI  - Intermittent urinary retention secondary to a uterine leiomyoma.
AB  - Urinary retention rarely affects reproductive-age women. In obstructive
      retention, the source must be determined and then removed to allow the patient to
      void normally. The most common causes of obstructive retention are gynecologic
      surgery and pelvic masses. Two women with intermittent urinary retention were
      evaluated in our clinic. Case 1 was a 48-year-old patient who voided frequently
      to avoid urinary retention. She had an ultrasound showing a large posterior
      leiomyoma. Case 2 was a 49-year-old female who presented with urinary retention
      during her menses. Magnetic resonance imaging result showed a large posterior
      leiomyoma deflecting the cervix anteriorly. Both women's urinary retention
      completely resolved after a total abdominal hysterectomy. Uterine leiomyomas may
      be the cause of urinary retention in reproductive-age females without other
      etiologies.

PMID- 16788852
TI  - Outcome of transvaginal radiofrequency for treatment of women with stress urinary
      incontinence.
AB  - The objective of the study was to assess the outcome and patient acceptance of
      the transvaginal radiofrequency bladder neck suspension procedure. A
      retrospective chart review of 18 women treated with the transvaginal
      radiofrequency bladder neck suspension procedure for stress urinary incontinence
      was conducted. Data on demographics, urodynamics, daily leakage episodes,
      complications, patient satisfaction, and further intervention were collected. The
      mean number of leaks per day was 5.7. There were no complications.
      Postoperatively, two patients were continent, four were improved, and ten were
      unimproved. The mean number of daily leaks was reduced to 2.7. Five patients
      reported to be extremely satisfied with the procedure. One patient was satisfied,
      and ten were not satisfied. Seven patients sought additional treatment within 1
      year. Low cure rate, low patient satisfaction, and high rate of additional
      treatment led us to discontinue transvaginal radiofrequency bladder neck
      suspension procedure as a treatment option. It is important that long-term
      outcome data of the initial studies be made public.

PMID- 16788853
TI  - Higher 1,25-dihydroxyvitamin D3 concentrations associated with lower fall rates
      in older community-dwelling women.
AB  - INTRODUCTION: The purpose of this study was to examine the relationships of
      vitamin D supplementation and serum concentrations of vitamin D metabolites and
      parathyroid hormone (PTH) with neuromuscular function and falls in older
      community-dwelling women. METHODS: We examined these relationships using a 4-year
      prospective multi-center study among 9,526 community-dwelling women enrolled in
      the Study of Osteoporotic Fractures (median age: 70 years; interquartile range:
      67-75) and a subset of 389 women (97%) out of 400 who were randomly selected from
      the entire cohort for serum measures. Measurements included: vitamin D
      supplementation, serum 25-hydroxyvitamin D(3) [25(OH)D(3)], serum 1,25
      dihydroxyvitamin D(3) [1,25(OH) (2)D(3)], and serum intact parathyroid hormone
      (iPTH); grip and quadriceps strength, chair-stand time, walking speed, reaction
      time, and balance-walk time (including changes in grip strength, chair-stand
      time, walking speed and balance-walk time over approximately 3.7 years); and
      incident fall rates (number of falls/woman-years). RESULTS: In 9,526 women,
      vitamin D supplementation was not associated with any measures of neuromuscular
      function, change in neuromuscular function, or fall rates (p>0.01 for all). In a
      subgroup of 389 women, there was a trend of higher 25(OH)D(3) concentration with
      slightly weaker grip strength (p=0.007), and women in the fourth quartile of
      1,25(OH)(2)D(3) had a faster chair-stand time (p=0.017) than women in the first
      quartile; still, in general, concentrations of 25(OH)D(3), 1,25(OH)(2)D(3), and
      iPTH were not associated with either neuromuscular function or changes in
      neuromuscular function (p>0.05 for all). However, higher 1,25(OH)(2)D(3)
      concentration was associated with lower fall rates (p=0.039). CONCLUSIONS: Higher
      1,25(OH)(2)D(3) concentration is associated with a lower fall risk in older
      community-dwelling women, but vitamin D supplementation, and 25(OH)D(3) and iPTH
      concentrations are not associated with either neuromuscular function or falls.

PMID- 16788854
TI  - Succinic semialdehyde dehydrogenase (SSADH) deficiency: Molecular analysis in a
      South American family.
AB  - We report the clinical, biochemical and molecular findings on the first
      documented patient with 4-hydroxybutyric aciduria (4-HBA, McKusick 271980) from
      Uruguay. The patient displayed a severe picture and turned out to be homozygous
      for a mutation (c.1226G < A) previously shown to be associated with null enzyme
      activity.

PMID- 16788855
TI  - Toward reversal of eutrophic conditions in a subtropical estuary: water quality
      and seagrass response to nitrogen loading reductions in Tampa Bay, Florida, USA.
AB  - Coastal waters have been significantly influenced by increased inputs of
      nutrients that have accompanied population growth in adjacent drainage basins. In
      Tampa Bay, Florida, USA, the population has quadrupled since 1950. By the late
      1970s, eutrophic conditions including phytoplankton and macroalgal blooms and
      seagrass losses were evident. The focus of improving Tampa Bay is centered on
      obtaining sufficient water quality necessary for restoring seagrass habitat,
      estimated to have been 16,400 ha in 1950 but reduced to 8800 ha by 1982. To
      address these problems, targets for nutrient load reductions along with seagrass
      restoration goals were developed and actions were implemented to reach adopted
      targets. Empirical regression models were developed to determine relationships
      between chlorophyll a concentrations and light attenuation adequate for
      sustainable seagrass growth. Additional empirical relationships between nitrogen
      loading and chlorophyll a concentrations were developed to determine how Tampa
      Bay responds to changes in loads. Data show that when nitrogen load reduction and
      chlorophyll a targets are met, seagrass cover increases. After nitrogen load
      reductions and maintenance of chlorophyll a at target levels, seagrass acreage
      has increased 25% since 1982, although more than 5000 ha of seagrass still
      require recovery. The cooperation of scientists, managers, and decision makers
      participating in the Tampa Bay Estuary Program's Nitrogen Management Strategy
      allows the Tampa Bay estuary to continue to show progress towards reversing many
      of the problems that once plagued its waters. These results also highlight the
      importance of a multi-entity watershed management process in maintaining progress
      towards science-based natural resource goals.

PMID- 16788856
TI  - Ten key questions about the management of water in the Yellow River basin.
AB  - Water is scarce in many regions of the world, clean water is difficult to find in
      most developing countries, there are conflicts between irrigation needs and urban
      demands, and there is wide debate over appropriate means of resolving these
      problems. Similarly, in China, there is limited understanding of the ways in
      which people, groups, and institutions contribute to, are affected by, and
      respond to changes in water quantity and quality. We use the example of the
      Yellow River basin to argue that these social, managerial, and policy dimensions
      of the present water problems are significant and overshadow the physical ones.
      Despite this, they receive relatively little attention in the research agenda,
      particularly of the lead agencies in the management of the Yellow River basin. To
      this end, we ask ten research questions needed to address the policy needs of
      water management in the basin, split into two groups of five. The first five
      relate to the importance of water in this basin and the changes that have
      affected water problems and will continue to do so. The second five questions
      represent an attempt to explore possible solutions to these problems.

PMID- 16788857
TI  - Quality and quantity of leachate in aerobic pilot-scale landfills.
AB  - In this study, two pilot-scale aerobic landfill reactors with (A1) and without
      (A2) leachate recirculation are used to obtain detailed information on the
      quantity and quality of leachate in aerobic landfills. The observed parameters of
      leachate quality are pH, chloride (Cl-), chemical oxygen demand (COD), biological
      oxygen demand (BOD), total Kjeldahl nitrogen (TKN), ammonia nitrogen (NH3-N), and
      nitrate (NO3(-)-N). pH values of the leachate increased to 7 after 50 days in
      reactor A1 and after 70 days in reactor A2. Cl- concentrations increased rapidly
      to 6100 (A1) and 6900 (A2) mg/L after 80 days, from initial values of 3000 and
      2800 mg/L, respectively. COD and BOD values decreased rapidly in the A1 landfill
      reactor, indicating the rapid oxidation of organic matter. The BOD/COD ratio
      indicates that leachate recirculation slightly increases the degradation of solid
      waste in aerobic landfills. NH3-N concentrations decreased as a result of the
      nitrification process. Denitrification occurred in parts of the reactors as a
      result of intermittent aeration; this process causes a decrease in NO3(-)
      concentrations. There is a marked difference between the A1 and A2 reactors in
      terms of leachate quantity. Recirculated leachate made up 53.3% of the leachate
      generated from the A1 reactor during the experiment, while leachate quantity
      decreased by 47.3% with recirculation when compared with the aerobic dry landfill
      reactor.

PMID- 16788858
TI  - Effects of bioengineered streambank stabilization on bank habitat and
      macroinvertebrates in urban streams.
AB  - Non-structural streambank stabilization, or bioengineering, is a common stream
      restoration practice used to slow streambank erosion, but its ecological effects
      have rarely been assessed. We surveyed bank habitat and sampled bank
      macroinvertebrates at four bioengineered sites, an unrestored site, and a
      comparatively less-impacted reference site in the urban Peachtree-Nancy Creek
      catchment in Atlanta, GA, USA. The amount of organic bank habitat (wood and
      roots) was much higher at the reference site and three of the bioengineered sites
      than at the unrestored site or the other bioengineered site, where a very
      different bioengineering technique was used ("joint planting"). At all sites, we
      saw a high abundance of pollution-tolerant taxa, especially chironomids and
      oligochaetes, and a low richness and diversity of the bank macroinvertebrate
      community. Total biomass, insect biomass, and non-chironomid insect biomass were
      highest at the reference site and two of the bioengineered sites (p < 0.05).
      Higher biomass and abundance were found on organic habitats (wood and roots)
      versus inorganic habitats (mud, sand, and rock) across all sites. Percent organic
      bank habitat at each site proved to be strongly positively correlated with many
      factors, including taxon richness, total biomass, and shredder biomass. These
      results suggest that bioengineered bank stabilization can have positive effects
      on bank habitat and macroinvertebrate communities in urban streams, but it cannot
      completely mitigate the impacts of urbanization.

PMID- 16788859
TI  - Time series forecasting of cyanobacteria blooms in the Crestuma Reservoir (Douro
      River, Portugal) using artificial neural networks.
AB  - In this work, time series neural networks were used to predict the occurrence of
      toxic cyanobacterial blooms in Crestuma Reservoir, which is an important potable
      water supply for the Porto region, located in the north of Portugal. These models
      can potentially be used to provide water treatment plant operators with an early
      warning for developing cyanobacteria blooms. Physical, chemical, and biological
      parameters were collected at Crestuma Reservoir from 1999 to 2002. The data set
      was then divided into three independent time series, each with a fortnightly
      periodicity. One training series was used to "teach" the neural networks to
      predict results. Another series was used to verify the results, and to avoid over
      fitting of the data. An additional independently collected data series was then
      used to test the efficacy of the model for predicting the abundance of
      cyanobacteria. All of the models tested in this study incorporated a prediction
      time (look-ahead parameter) equal to the sampling interval (two weeks). Various
      lag periods, from 2 to 52 weeks, were also investigated. The best model produced
      in this study provided the following correlations between the target and forecast
      values in the training, verification, and validation series: 1.000 (P = 0.000),
      0.802 (P = 0.000), and 0.773 (P = 0.001), respectively. By applying this model to
      the three-year data set, we were able to predict fluctuations in cyanobacteria
      abundance in the Crestuma Reservoir, with a high level of precision. By
      incorporating a lag-period of eight weeks, we were able to detect secondary
      fluctuations in cyanobacterial abundance over the annual cycle.

PMID- 16788860
TI  - Implications of land use/land cover change in the buffer zone of a national park
      in the tropical Andes.
AB  - The impacts of land use and land cover (LULC) change in buffer zones surrounding
      protected ecological reserves have important implications for the management and
      conservation of these protected areas. This study examines the spatial and
      temporal patterns of LULC change along the boundary of Rio Abiseo National Park
      in the Northern Peruvian Andes. Landscape change within four ecological zones was
      evaluated based on trends expected to occur between 1987 and 2001. Landsat TM and
      ETM imagery were used to produce LULC classification maps for both years using a
      hybrid supervised/unsupervised approach. LULC changes were measured using
      landscape metrics and from-to change maps created by post-classification change
      detection. Contrary to expectations, tropical upper wet montane forest increased
      despite being threatened by human-induced fires and cattle grazing of the
      highland grasslands inside the park. Within the park's buffer zone, tropical
      moist forest remnants were fragmented into more numerous and smaller patches
      between 1987 and 2001; this was in part due to conversion into agricultural land.
      The methods used in this study provide an effective way to monitor LULC change
      detection and support the management of protected areas and their surrounding
      environments.

PMID- 16788861
TI  - A Phase I study of the oral antimetabolite, CS-682, administered once daily 5
      days per week in patients with refractory solid tumor malignancies.
AB  - The development of nucleoside analogues has had a major impact on cancer therapy.
      CS-682 is a novel, orally administered nucleoside analogue with a unique
      mechanism of action. CS-682 undergoes conversion to the active metabolite, CNDAC,
      which then leads to the inhibition of DNA polymerase and a novel "DNA self-strand
      breaking mechanism." We conducted a Phase I study of CS-682, administered orally
      five days per week in patients with refractory solid tumor malignancies. Forty
      eight patients were enrolled on study. The recommended phase II dose of 30
      mg/m(2) given orally once daily for 5 days a week for 4 weeks followed by 2 weeks
      off drug, was well tolerated. The most common dose limiting toxicity was
      neutropenia, which occurred at the highest dose levels of CS-682. This was
      correlated with higher CNDAC Cmax and AUC values. No tumor responses were noted
      in this heavily pretreated population. However, given the ease of administration
      and tolerability, further investigation of this agent is warranted.

PMID- 16788862
TI  - Downregulation of the PI3K/Akt survival pathway in cells with deregulated
      expression of c-Myc.
AB  - Oncogenic transformation leads to an increased sensitivity to apoptosis, a
      characteristic that is selectively lost during tumor progression. The
      sensitization process affects the mitochondrial pathway of apoptosis through
      signaling events that are poorly defined. We previously showed that a deregulated
      expression of c-Myc in cells treated with toxic agents caused an enhanced
      activation of p38 that acts in a death-promoting pathway. Here, we show that
      deregulated expression of c-Myc causes a severe reduction in the basal activity
      of Akt, which was further accelerated by serum deprivation. Furthermore, c-Myc
      expression repressed the activation of Akt induced by the toxic agents
      doxorubicin, cisplatin and H(2)O(2), and also by the physiological agonists PDGF
      and insulin. We determined that the activation of Akt was inhibited as a result
      of the action of c-Myc upstream of phosphatidylinositol 3-kinase (PI3K)
      activation. c-Myc overexpression impaired the induced association of the p85
      subunit of PI3K with phosphotyrosine containing proteins, causing a reduction in
      the activation of PI3K and recruitment of Akt to the membrane. Inhibiting Akt in
      addition to enhancing p38 further exacerbate the imbalance between the death and
      survival signals and results in an enhanced sensitivity to apoptosis.

PMID- 16788863
TI  - [SPECT and PET in neurology].
AB  - Both single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) are helpful in the practice of neurology. Ictal SPECT is useful
      to determine the origin of focal seizures in the pre-surgical evaluation. In some
      centers, it is used to predict the likelihood of massive cerebral swelling after
      stroke and of cerebral infarction after a subarachnoid hemorrhage. It has also
      been used to study dopaminergic function in parkinsonian syndromes and in the
      evaluation of dementia. Given its higher resolution and some other factors, PET
      is more useful in the evaluation of brain tumors, dementia and the parkinsonian
      syndromes. It is also useful in the presurgical evaluation of epilepsy.

PMID- 16788864
TI  - [The utility of interictal SPECT in temporal lobe epilepsy].
AB  - INTRODUCTION: Interictal brain single photon emission computed tomography (SPECT)
      is used in the presurgical evaluation of patients with complex partial epilepsy.
      The aim of the present study was to compare interictal SPECT, MRI and video
      electroencephalography (EEG) for seizure focus localization in patients with
      temporal lobe epilepsy, one year after temporal lobectomy, in order to determine
      the utility of interictal brain SPECT. PATIENTS AND METHODS: Thirty four
      consecutive patients with refractory temporal epilepsy were evaluated with video
      EEG, MRI and interictal SPECT for seizure focus localization before surgery.
      Seizure focus was confirmed with the clinical follow-up one year after temporal
      lobectomy in all patients. MRI and SPECT analysis was performed visually.
      RESULTS: 31/34 patients were seizure free one year after surgery and the
      remaining 3 patients remain with seizures occasionally. Video-EEG results
      coincided with postsurgical seizure focus localization in 31 (91%) patients. MRI
      localized seizure focus correctly in 30 (88%) patients and was normal in 3 cases.
      Interictal brain SPECT was normal in 10 patients and showed temporal
      hypoperfusion consistent with postsurgical seizure focus in 23 (68%) patients. In
      all patients with abnormalities in the interictal SPECT, seizure focus was
      identified with video-EEG or MRI. CONCLUSIONS: When MRI and video-EEG localize
      seizure focus in the same temporal lobe, interictal brain SPECT does not offer
      any additional information for surgical decision making.

PMID- 16788865
TI  - [Adverse drug events in out-patients as the cause of an initial consultation to
      neurology].
AB  - INTRODUCTION: The aim of this study was to determine the incidence and type of
      neurological adverse drug events as the cause of an initial consultation to
      neurology, identify the medications involved and evaluate the possibilities of
      prevention. METHODS: Prospective observational study lasting 1 year (February 10,
      2004 to February 9, 2005) that included all new adult outpatients at a neurology
      ward. Suspected adverse drug events were evaluated by two investigators in order
      to establish causality relationships, severity, preventability and types of
      medication errors associated with the preventable cases. RESULTS: In a total of
      685 patients who attended the neurology consult, 60 neurological adverse drug
      events were detected (8.7%), of which 70% were moderate and 30% mild. The most
      frequent adverse events detected were medication overuse headache (51.6%), mainly
      due to acetaminophen and ergot derivatives, and drug-induced Parkinsonism
      (33.3%), especially related to trimetazidine or sulpiride. Fifty-five adverse
      events (91.6%) were considered potentially preventable. Medication errors
      associated were overuse and self-medication (33.7 %), failure to follow treatment
      adequately (25.6%), excessive duration of treatment (16.3%) and prescribing an
      unnecessary medication (14.0%) or an inappropriate one (10.5%). CONCLUSIONS: The
      incidence of adverse drug events motivating an initial visit to a neurologist is
      high and the majority of these cases are preventable. Greater knowledge on the
      part of physicians concerning medication overuse headache and drugs that induce
      Parkinsonism, as well as public health education on the risks involved with the
      use of analgesics, could contribute to prevention.

PMID- 16788866
TI  - [Incontinentia pigmenti: clinical and neuroimaging findings in a series of 12
      patients].
AB  - OBJECTIVE: To describe the clinical, neuroimaging 51 with magnetic resonance
      imaging (MRI) and evolutive findings in 12 patients with incontinentia pigmenti
      (IP). Five patients show cutaneous and neurological lesions and seven only show
      cutaneous lesions without neurologic or/ and ophthalmologic abnormalities.
      MATERIAL AND METHODS: Five mothers and seven daughters from four families were
      studied and followed between 1965 and 2004. The studies consisted of detailed
      clinical history since birth, physical examination, family history, EEG
      recordings and MRI studies. In some patients, at least three MRI studies were
      performed during our follow-up. All patients were followed-up since their first
      visit until 2004. Including four patients since birth or early infancy. Skin
      biopsies were obtained from two infants for histological study. RESULTS: MRI
      studies revealed brain abnormalities in five girls who had neurologic signs
      associated with the cutaneous lesions of IP. Brain lesions were bilateral in four
      and unilateral in one. Cerebellar changes were observed only in one case who also
      showed severe cerebral lesions. The lesions involved cortex, subcortical and deep
      white matter, ependymal and subependymal zones of one or both cerebral
      hemispheres. Lesions usually were localized and extended radially to involve all
      the cerebral parenchyma between ependyma and cortex. Affected areas did not
      correspond to territories vascularized by any determined artery. The corpus
      callosum showed generalized or localized atrophy in the five patients who had
      cerebral hemispheric lesions. Although parenchymal changes were seen in both the
      T1 and T2 weighted images, these were most evident in the latter. Parenchymal
      abnormalities were most severe in patients with neonatal severe cutaneous
      lesions, especially if these were located in the scalp. Cerebral lesions were
      present from birth or the first months of life and changed little thereafter. The
      acute appearance and distribution of cerebral lesions always during the neonatal
      period, associated with scalp lesions in stage 1, suggest an acute inflammatory
      origin of unknown etiology and of nonprogressive course. Ocular lesions were
      directly related with cerebral abnormalities. Patients who only had cutaneous
      lesions without neurologic symptoms showed no MRI abnormalities. CONCLUSIONS:
      Neuroimaging studies reveals brain lesions only in patients with neurologic
      disease in this serie. The brain lesions may involve one or both cerebral
      hemispheres, corpus callosum, and cerebellum. The brain lesions correlate with
      the neonatal scalp lesions in stage 1, suggests an inflammatory process of
      unknown etiology and non-progressive course. The appearance and distribution of
      the cerebral lesions do not follow the territories vascularized by specific
      arteries. Ocular lesions are observed only in patients with severe cerebral
      changes. Early onset of cerebral lesions may be the most reasonable explanation
      for the progressive microcephaly within the first year of life in IP.

PMID- 16788867
TI  - [Infection by Epstein-Barr virus and multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis is the most important disabling neurological
      disease in young adulthood in our environment. However, its etiology remains
      unknown. It has been proposed that multiple sclerosis is caused by an interaction
      of genetic and environmental factors. In particular, Epstein-Barr virus infection
      could play a fundamental role in the pathophysiology of multiple sclerosis.
      METHODS: We have reviewed the most recent and important bibliography, both from
      epidemiologic and basic research studies, dealing with the possible association
      between Epstein-Barr virus infection and multiple sclerosis. RESULTS:
      Retrospective and prospective epidemiologic studies suggest a direct association
      between Epstein-Barr virus infection and the risk of multiple sclerosis. Several
      physiopathologic mechanisms, including molecular mimicry and bystander
      activation, could be responsible for this association. CONCLUSIONS: Based on the
      published evidence, Epstein-Barr virus infection can be considered to have a
      causal role in the etiology of multiple sclerosis. Further research should be
      conducted to elucidate the mechanisms underlying this association and to assess
      its potential for multiple sclerosis prevention and treatment.

PMID- 16788868
TI  - [Norman-Jaeken cerebellar atrophy].

PMID- 16788869
TI  - [Cortical laminar necrosis caused by cerebral infarction].

PMID- 16788870
TI  - [Ischemic stroke and cardiac myxomas. Findings in cranial magnetic resonance
      imaging].
AB  - INTRODUCTION: We report three patients with ischemic stroke as initial
      manifestation of left atrial myxomas. CASES REPORTED: Case 1: man with difficulty
      in speaking for 15 minutes at the age of 33 years and dysarthria, right
      hemiparesis and hemisensory loss at the age of 36. Case 2: woman aged 29 with
      facial weakness and left limbs weakness for an hour. Case 3: woman with transient
      vertigo and paresthesia in right hemiface and upper limb for a month at the age
      of 35 years and difficulty for speaking, weakness of right limbs and loss of
      vision in left eye at the age of 40 years. The three patients had an atrial
      myxoma diagnosed by transthoracic or transesophageal echocardiography.
      CONCLUSIONS: The three patients had ischemic stroke at a young age. The initial
      manifestation of the myxoma was a transient ischemic attack in two of them.
      Diagnosis was delayed more than 3 years in two of the patients. The second
      episode of the third patient affected all the left internal carotid territory
      including the posterior cerebral artery arising from the internal carotid and
      branches of the central retinal artery. Comparing the magnetic resonance with the
      previous one, new hyperintense images on T2 with gadolinium enhancement were
      found in the left hemisphere consistent with subacute infarcts that had
      stabilized 5 months later.

PMID- 16788871
TI  - [Solitary costal plasmacytoma: a rare cause of subacute demyelinating
      polyradiculoneuropathy].
AB  - INTRODUCTION: The solitary plasmacytoma (SP) is a non-frequent, localized variant
      of multiple myeloma with a single bone lesion and earlier appearance.
      Polyradiculoneuropathy is the most frequent neurological manifestation. We report
      the case of a young male who developed a subacute demyelinating
      polyradiculoneuropathy as the initial symptomatology of a costal SP, which
      constitutes an extremely infrequent association, given age and site of the
      lesion. CASE REPORT: A 32-year old, previously healthy, man presented with a one
      month history of progressive symmetrical paraparesis and paresthesias in feet.
      The neurological examination revealed 4/5 paraparesis, global arreflexia and
      hypopalesthesia in legs. Cerebrospinal fluid examination revealed elevated
      proteins (83 mg/dl) with normal cell count and glucose content. Investigations
      showed high levels of beta(2)-microglobulin (3 mg/l), and a monoclonal IgG lambda
      gammapathy. The chest X-ray and thoracic CT revealed an osteolytic lesion in the
      left third rib. Nerve conduction studies showed sensitive and motor
      polyneuropathy with secondary axonal degeneration. Bone marrow biopsy was normal.
      Second and third left ribs were excised, revealing a pathologic diagnosis of
      plasmacytoma. The patient became asymptomatic after corticosteriod administration
      lesion excision and local radiotherapy. Conclusions. Subacute demyelinating
      polyradiculoneuropathy can be due to multiple causes. SP can be one of its
      etiologies and occur at infrequent ages and localizations.

PMID- 16788872
TI  - [Partial occipital seizures as main symptom of posterior encephalopathy secondary
      to immunosuppresants].
AB  - INTRODUCTION: Reversible posterior leukoencephalopathy syndrome (RPLS) affects
      patients who are following immunosupressive treatment. It can affect children
      too, it can be irreversible and occipital seizures can be the main manifestation.
      We describe the EEG of five children who presented occipital seizures due to
      posterior leukoencephalopathy syndrome secondary to treatment with
      immunosupressives. They had different clinico- electrical evolutions. CASES
      REPORTS: Five children aged from 18 months to 11 years who had been treated with
      bone marrow, liver or kidney transplantation and one or two immunosupressive
      drugs: cyclosporine, tacrolimus. 4-50 days after the transplantation they
      presented arterial hypertension and low conscience. Occipital seizures or status
      were registered in EEG. Neuroimaging showed edema lesions in posterior regions.
      They were treated with antihipertensives, antiepileptics and substitution or
      reduction of immunosupressive drugs doses. Two patients presented further
      episodes and three of them had persistent abnormal EEG. Two patients had more
      than one status even though Cys A had been replaced by Tacrolimus or because the
      drug dose had not been modified. The Immunosupressive drugs are necessary for the
      transplantation's good outcome and they cannot be easily stopped. CONCLUSIONS:
      Low conscience level and oculoclonic movements may form part of the subtle clinic
      of the occipital seizures, that may be the main manifestation of PLS in children
      who are following immunosupressor treatment. The realization of an EEG is
      indispensable for a quick diagnose and in order to achieve the reversibility of
      the syndrome. If we cannot get it, EEG will be useful for the evolution follow-up
      too.

PMID- 16788874
TI  - [What's Your Diagnosis?]

PMID- 16788873
TI  - [Hemifacial spasm in Egyptian art].

PMID- 16788875
TI  - ?

PMID- 16788876
TI  - ?

PMID- 16788878
TI  - ?

PMID- 16788877
TI  - ?

PMID- 16788879
TI  - ?

PMID- 16788880
TI  - ?

PMID- 16788882
TI  - ?

PMID- 16788881
TI  - ?

PMID- 16788883
TI  - ?

PMID- 16788884
TI  - ?

PMID- 16788885
TI  - ?

PMID- 16788887
TI  - NMR spectroscopic structure elucidation of the products of the reaction of 3-(3
      aryl-3-oxopropenyl)- chromen-4-ones with 1,2-phenylenediamine.
AB  - The reaction of 3-(3-aryl-3-oxopropenyl)chromen-4-ones with 1,2-phenylenediamine
      resulted in the unexpected formation of 10a-aryl-1,2,10,10a-tetrahydrobenzo-[4,5]
      imidazo[1,2-a]pyridin-3-yl(2-hydroxyphenyl)-1-methanones. Their structure
      elucidation and complete 1H and 13C assignments have been performed by a
      combination of various one- and two-dimensional NMR experiments.

PMID- 16788888
TI  - Temperature and solvent dependent NMR studies on mangiferin and complete NMR
      spectral assignments of its acyl and methyl derivatives.
AB  - By employing concerted 1 and 2D NMR techniques, exact NMR spectral assignments
      have been made of the acyl (2-7) and methyl (8 and 9) derivatives of mangiferin
      (1) isolated from the leaves of Bombax ceiba. Derivatives 2, 8 and 9 have been
      reported in literature, while 3-7 represent new compounds. The acetates 2 and 3
      were found to be unstable and were converted into the same penta-acetate 4 at
      room temperature. Extensive NMR studies on mangiferin (1) and its derivatives
      showed that H-4 exchanges with deuterium of the solvent molecule more easily.
      This exchange under acidic conditions occurred at that position (C-4) where
      electrophilic substitution reactions can easily take place. This is the first
      report describing the exchange of C-4 proton of mangiferin (1), or any other
      xanthone, with deuterium of solvent molecules.

PMID- 16788889
TI  - Explaining sex differences in dental caries prevalence: saliva, hormones, and
      "life-history" etiologies.
AB  - When dental caries rates are reported by sex, females are typically found to
      exhibit higher prevalence rates than males. This finding is generally true for
      diverse cultures with different subsistence systems and for a wide range of
      chronological periods. Exceptions exist, but are not common. In this paper, we
      present new data for sex differences in dental caries rates among the Guanches
      (Tenerife, Canary Islands), summarize results of meta-analyses of dental caries
      prevalence, and emphasize new research that stresses the critical role of female
      hormones and life-history events in the etiology of dental caries. Among the
      Guanches, corrected tooth-count caries rates for females (8.8%, 158/1,790) are
      approximately twice the frequency of caries among males (4.5%, 68/1,498). Higher
      caries prevalence among females is often explained by one of three factors: 1)
      earlier eruption of teeth in girls, hence longer exposure of girls' teeth to the
      cariogenic oral environment, 2) easier access to food supplies by women and
      frequent snacking during food preparation, and 3) pregnancy. Anthropologists tend
      to favor explanations involving behavior, including sexual division of labor and
      women's domestic role in food production. By contrast, the causal pathways
      through which pregnancy contributes to poorer oral health and higher caries rates
      are deemphasized or discounted. This paper presents recent research on
      physiological changes associated with fluctuating hormone levels during
      individual life histories, and the impact these changes have on the oral health
      of women. The biochemical composition of saliva and overall saliva flow rate are
      modified in several important ways by hormonal fluctuations during events such as
      puberty, menstruation, and pregnancy, making the oral environment significantly
      more cariogenic for women than for men. These results suggest that hormonal
      fluctuations can have a dramatic effect on the oral health of women, and
      constitute an important causal factor in explaining sex differences in caries
      rates.

PMID- 16788890
TI  - Apolipoprotein E polymorphism and neuronal plasticity.

PMID- 16788891
TI  - p.Q223R leptin receptor polymorphism associated with obesity in Brazilian
      multiethnic subjects.
AB  - Several genes play a major role in obese phenotypes, and studies suggest that
      genetic variations among individuals, as well as their lifestyles, may bring
      about different body compositions. Among these genes, LEP, which codifies leptin,
      and the LEPR gene encoding its receptor were extensively studied for variants
      that could explain the obese phenotype. The LEPR p.Q223R gene polymorphism was
      analyzed in a sample of obese and nonobese individuals from Brazil to evaluate
      the role of this polymorphism in the obese phenotype in the population. Two
      hundred obese patients (60 males, 140 females, body mass index (BMI) >30 kg/m2)
      were screened, together with 150 lean or normal healthy individuals (63 males, 87
      females, BMI <24 kg/m2). Genomic DNA was extracted and amplified by polymerase
      chain reaction (PCR). PCR products were digested with the restriction of
      endonuclease MspI, and separated by electrophoresis through an 8% polyacrilamide
      gel stained with silver nitrate. There was a significant difference in LEPR
      p.Q223R polymorphism frequency when comparing obese and lean subjects, with an
      odds ratio of 1.92 and a 95% confidence interval of 1.15-3.22 (P = 0.013). There
      is a strong association of the LEPR p.Q223R gene polymorphism with obesity in
      Brazil.

PMID- 16788892
TI  - Methodological agreement between two-compartment body-composition methods in
      children.
AB  - Increases in childhood obesity have emphasized the importance of accurate and
      accessible body composition assessment, especially in monitoring prevention and
      treatment efforts. Previous pediatric studies, comparing measures from air
      displacement plethysmography (ADP) to dual-energy X-ray absorptiometry (DXA) and
      anthropometry (ANTH, skinfold measures), were performed in small numbers of
      children or in children across large age and body-size ranges. The objectives of
      this study were: 1) to compare body fat percentage (%BF), fat mass (FM), and fat
      free mass (FFM) from ADP with DXA and ANTH, to determine the agreement between
      techniques; 2) to identify factors that influence agreement or lack of agreement;
      and 3) to determine if the agreement is constant over a range of body fatness.
      Healthy children (n = 125), 7-10 years old, participating in a longitudinal
      pediatric bone health study, were evaluated. Body composition was assessed by
      ADP, DXA, and ANTH to determine %BF, FM, and FFM. ADP underestimated %BF compared
      to DXA and ANTH by 5.0% and 1.4%, respectively. Agreement between techniques was
      influenced by body fatness, height, age, and gender (all P < 0.05). Relatively
      good agreement was observed between ADP and both DXA and ANTH for FM and FFM. In
      conclusion, the underestimation of %BF by ADP compared to DXA may be of a
      magnitude that is clinically significant, especially when using %BF in children
      to confirm a diagnosis of obesity. Further development of body-composition
      techniques for young children need to account for variability in age, gender, and
      level of fatness.

PMID- 16788893
TI  - A statistical overview on univariate calibration, inverse regression, and
      detection limits: Application to gas chromatography/mass spectrometry technique.
AB  - The paper summarizes critically the current approaches for the calculation of the
      limits of detection and quantification. In the context of the description of the
      method based on the calibration line, the arguments concerning the underlying
      experimental design, the choice of the appropriate model in the univariate
      regression, the effects of the dispersion characteristics of the data are deeply
      discussed. The effects of the scedasticity of the experimental data are taken
      into account in the obtainment of the calibration curve and in its utilization.
      To gain transparency, adaptability, and tutorial effectiveness the explicit
      formulas relevant to the use of straight line and quadratic models are reported.
      An application of the described procedures to GC-MS data is reported as an
      illustrative example.

PMID- 16788894
TI  - Genetic structure of Algerian populations.
AB  - Blood samples were collected in Algeria from 4,444 army recruits and tested for
      10 genetic polymorphic systems. These samples were collected from territorial
      Wilayas (administrative units of Algeria) from which the young soldiers had
      originated. Based on similar geography and economic and political history, these
      Wilayas were clustered into 10 regions. These regions, not part of the
      governmental administrative units, were characterized by allelic frequencies, and
      analyzed using R-matrix principal components, Wright's F(ST), spatial
      autocorrelation, and Mantel tests. Hierarchical relationships between the
      culturally defined regions were examined using two different analytical methods
      of phylogenetic tree constructions: neighbor-joining, and unweighted pair group
      average arithmetic (UPGMA). These results indicated the predominance of genetic
      homogeneity due to the gene flow between regions, but with some migration
      emanating from sub-Saharan Africa and Mediterranean Europe. Wright's F(ST) value
      of 0.0063, based on 16 alleles, suggested a relatively small genetic
      microdifferentiation of the regions. In Algeria, gene flow apparently swamped
      most of the effects of stochastic processes and disrupted the relationship
      between geography and genetics, as characterized by the isolation-by-distance
      model. Some genetic differences and similarities were observed between regions or
      clusters of regions. The resulting genetic structure of the Algerian populations
      is best explained by a combination of gene flow, ecology, and history.

PMID- 16788895
TI  - Population structure and admixture in Cerro Largo, Uruguay, based on blood
      markers and mitochondrial DNA polymorphisms.
AB  - Recent studies of the Uruguayan population revealed different amounts of
      Amerindian and African genetic contributions. Our previous analysis of Afro
      Uruguayans from the capital city of the Department of Cerro Largo showed a high
      proportion of African genes, and the effects of directional mating involving
      Amerindian women. In this paper, we extended the analysis to a sample of more
      than 100 individuals representing a random sample of the population of the whole
      Department. Based on 18 autosomal markers and one X-linked marker, we estimated
      82% European, 8% Amerindian, and 10% African contributions to their ancestry,
      while from seven mitochondrial DNA site-specific polymorphic markers and
      sequences of hypervariable segment I, we determined 49% European, 30% Amerindian,
      and 21% African maternal contributions. Directional matings between Amerindian
      women and European men were detected, but differences involving Africans were not
      significant. Data about the specific origins of maternal lineages were also
      provided, and placed in a historical context.

PMID- 16788896
TI  - Do large dogs die young?
AB  - In most animal taxa, longevity increases with body size across species, as
      predicted by the oxidative stress theory of aging. In contrast, in within-species
      comparisons of mammals and especially domestic dogs (e.g. Patronek et al., '97;
      Michell, '99; Egenvall et al., 2000; Speakman et al., 2003), longevity decreases
      with body size. We explore two datasets for dogs and find support for a negative
      relationship between size and longevity if we consider variation across breeds.
      Within breeds, however, the relationship is not negative and is slightly, but
      significantly, positive in the larger of the two datasets. The negative across
      breed relationship is probably the consequence of short life spans in large
      breeds. Artificial selection for extremely high growth rates in large breeds
      appears to have led to developmental diseases that seriously diminish longevity.

PMID- 16788897
TI  - Lectin-binding pattern as tool to identify and enrich specific primary testis
      cells of the tilapia (Oreochromis niloticus) and medaka (Oryzias latipes).
AB  - Cell type-specific lectin binding is a useful tool for the analysis of developing
      systems. We describe the binding pattern of 21 different fluorescein
      isothiocyanate (FITC)-labelled lectins to the testis of two model teleost
      species, the medaka (Oryzias latipes) and the tilapia (Oreochromis niloticus).
      The analysis of the binding pattern was carried out on tissue sections (medaka
      and tilapia) and using primary culture cells (only tilapia). Lectin binding was
      studied by confocal microscopy and for histological analysis some sections were,
      in addition, stained with bodipy to gain additional information concerning the
      cytological organization of the cystic mode of spermatogenesis in fish. The
      observed differences in lectin staining of different cell types in primary
      cultures were quantified by flow cytometry. Only few lectins bound specifically
      to haploid cells while the reaction to diploid or tetraploid cells was generally
      stronger. However, the extracellular material around the haploid spermatids and
      spermatozoa in spermatocysts showed a strong staining reaction with several
      lectins (e.g., Phaseolus vulgaris Erythro agglutinin). The apparent differences
      in the cellular lectin-binding pattern can be used to identify particular cell
      types, to monitor their differentiation in vitro or to enrich particular cell
      types from heterogeneous cultures using magnetic beads coated with anti-FITC
      antibodies. Using the latter approach, we show that it is possible to enrich for
      gonial cells and at the same time deplete the preparation for haploid cells and
      Sertoli cells.

PMID- 16788898
TI  - High contents of hypotaurine and thiotaurine in hydrothermal-vent gastropods
      without thiotrophic endosymbionts.
AB  - Invertebrates at hydrothermal vents and cold seeps must cope with high levels of
      toxic H2S. In addition, these and all marine invertebrates must balance internal
      osmotic pressure with that of the ocean. Cells usually do so with organic
      osmolytes, primarily free amino acids (e.g., taurine, glycine) and methylamines
      (e.g., betaine). At vents and seeps, clams, mussels, and vestimentiferans with
      thiotrophic endosymbionts have high levels of hypotaurine and thiotaurine (a
      product of hypotaurine and HS-). These serve as osmolytes but their primary
      function may be to transport and/or detoxify sulfide; indeed, thiotaurine has
      been proposed to be a marker of thiotrophic symbiosis. To test this, we analyzed
      Depressigyra globulus snails and Lepetodrilus fucensis limpets from Juan de Fuca
      Ridge vents (1,530 m). Neither has endosymbionts, though the latter has
      thiotrophic ectosymbionts. Some specimens were rapidly frozen, while other live
      ones were kept in laboratory chambers, some with and others without sulfide. Non
      vent gastropods from a variety of depths (2-3,000 m) were also collected. Tissues
      were analyzed for major osmolytes and taurine derivatives. The dominant osmolytes
      of non-vent snails were betaine in all species, and either taurine in shallow
      living species or scyllo-inositol, glycerophosphorylcholine, and other amino
      acids in deep-sea species. In contrast, the dominant osmolytes were hypotaurine
      and betaine in D. globulus, and hypotaurine in L. fucensis. Both species had
      thiotaurine (as well as hypotaurine) at levels much greater than previously
      reported for vent and seep animals without endosymbionts. The ratio of thio- to
      thio- plus hypotaurine, a possible indicator of sulfide exposure, decreased in
      both species when kept in laboratory chambers with low or no sulfide, but stayed
      at high levels in snails kept with 3-5 mM sulfide. Thus, in some vent animals
      without endosymbionts, sulfide may be detoxified via conversion of hypotaurine to
      thiotaurine. The latter may be a marker of high sulfide exposure but not of
      thiotrophic endosymbionts.

PMID- 16788899
TI  - Neuroendocrine regulation of carbonic anhydrase expression in the gills of the
      euryhaline green crab, Carcinus maenas.
AB  - The relationship between branchial carbonic anhydrase (CA) activity, CA gene
      expression and salinity, and potential mechanisms of regulation, was investigated
      in the euryhaline green crab, Carcinus maenas, acclimated to 33 ppt and
      transferred to 10 ppt, and the stenohaline rock crab, Cancer irroratus,
      acclimated to 32 ppt and transferred to 18 ppt. CA activity in green crabs
      acclimated to high and low salinity was a function of CA mRNA expression, with
      low salinity exposure resulting in an increase in both CA expression and
      activity. Eyestalk ablation (ESA) in green crabs acclimated to high salinity
      resulted in an increase in CA expression in the posterior, ion-transporting
      gills, in the absence of the low salinity stimulus. There were no changes in CA
      activity or expression in the anterior, respiratory gills. ESA also potentiated
      low salinity-stimulated CA induction, again, only in posterior gills. There were
      no changes in CA activity in any gills of Cancer irroratus, in response to either
      ESA or low salinity. These results suggest that CA expression in euryhaline,
      osmoregulating species, is under inhibitory regulation by a putative repressor
      found in the eyestalk, and that this mechanism is absent in stenohaline,
      osmoconforming species. CA expression is maintained at low, baseline levels in
      crabs acclimated to high salinity by the presence and action of this compound.
      The effects of the repressor appear to be reduced upon exposure to low salinity,
      allowing CA induction to occur.

PMID- 16788900
TI  - Family composition and menarcheal age: anti-inbreeding strategies.
AB  - Family composition (e.g., the absence of a father) is associated with pubertal
      timing in women, although the socioendocrinology of the human primate is poorly
      understood. To better understand social influences on sexual maturation,
      retrospective data were collected on menarcheal age and family composition from a
      sample of approximately 1,938 participants from a college population. Absence of
      a biological father, the presence of half- and step-brothers, and living in an
      urban environment were associated with earlier menarche. The presence of sisters
      in the household while growing up, especially older sisters, was associated with
      delayed menarche. Menarcheal age was not affected by number of brothers in the
      household, nor was there an effect of birth order. Body weight and race were also
      associated with menarche. The present findings advance the literature as they are
      suggestive of putative human pheromones that modulate sexual maturation to
      promote gene survival and prevent inbreeding, as occurs in rodents and nonhuman
      primates.

PMID- 16788901
TI  - Functions of corticotropin-releasing hormone in anthropoid primates: from brain
      to placenta.
AB  - Corticotropin-releasing hormone (CRH) is an ancient regulatory molecule. The CRH
      hormone family has at least four ligands, two receptors, and a binding protein.
      Its well-known role in the hypothalamic-pituitary-adrenal (HPA) axis is only one
      of many. The expression of CRH and its related peptides is widespread in
      peripheral tissue, with important functions in the immune system, energy
      metabolism, and female reproduction. For example, CRH is involved in the
      implantation of fertilized ova and in maternal tolerance to the fetus. An
      apparently unique adaptation has evolved in anthropoid primates: placental
      expression of CRH. Placental CRH stimulates the fetal adrenal zone, an adrenal
      structure unique to primates, to produce dehydroepiandrosterone sulfate (DHEAS),
      which is converted to estrogen by the placenta. Cortisol induced from the fetal
      and maternal adrenal glands by placental CRH induces further placental CRH
      expression, forming a positive feedback system that results in increasing
      placental production of estrogen. In humans, abnormally high placental expression
      of CRH is associated with pregnancy complications (e.g., preterm labor,
      intrauterine growth restriction (IUGR), and preeclampsia). Within anthropoid
      primates, there are at least two patterns of placental CRH expression over
      gestation: monkeys differ from great apes (and humans) by having a midgestational
      peak in CRH expression. The functional significance of these differences between
      monkeys and apes is not yet understood, but it supports the hypothesis that
      placental CRH performs multiple roles during gestation. A clearer understanding
      of the diversity of patterns of placental CRH expression among anthropoid
      primates would aid our understanding of its role in human pregnancy.

PMID- 16788902
TI  - Cardiovascular factors explain genetic background differences in VO2max.
AB  - The purpose of this study was to further explore factors that may be related to
      ethnic differences in the maximum rate at which an individual can consume oxygen
      (VO2max) between 20 African American (AA) and 30 European American (EA) sedentary
      women who were matched for body weight (kg) and fat-free mass (FFM). VO2max
      (l/min) was determined during a graded treadmill exercise test. Submaximal steady
      state heart rate and submaximal VO2 were determined at a treadmill speed of 1.3
      m/sec and a 2.5% grade. Hemoglobin (Hb) was determined by the cyanide method,
      muscle oxidative capacity by 31P magnetic resonance spectroscopy (ADP time
      constant), and FFM (kg) by dual-energy x-ray absorptiometry. Genetic
      classification was self-reported, and in a subset of the sample (N = 32), the
      determinants of ethnicity were measured by African genetic admixture. AA women
      had significantly reduced VO2max, Hb levels, and muscle oxidative capacity
      (longer ADP time constants, P < or = 0.05) than EA women. Submaximal oxygen pulse
      (O2Psubmax), ADP time constant, Hb, and ethnic background were all significantly
      related to VO2max (ml/kg/min and ml/kg FFM/min, all P < or = 0.01). By multiple
      regression modeling, Hb, O2Psubmax, muscle oxidative capacity, and ethnicity were
      found to explain 61% and 57% of the variance of VO2max in ml/kg/min and ml/kg
      FFM/min, respectively. Muscle oxidative capacity and O2Psubmax were both
      significantly and independently related to VO2max in all three models (P < or =
      0.05), whereas Hb and ethnicity were not. These results suggest that
      mitochondrial muscle oxidative capacity and oxygen delivery capabilities, as
      determined by O2Psubmax, account for most if not all of the ethnic differences in
      VO2max.

PMID- 16788903
TI  - Asian and non-Asian origins of Mon-Khmer- and Mundari-speaking Austro-Asiatic
      populations of India.
AB  - In the present study, we analyzed 1,686 samples from 31 tribal populations of
      India for the mitochondrial DNA 9-base-pair deletion/insertion polymorphism, and
      characterized them based on the relevant mitochondrial DNA coding-region single
      nucleotide polymorphisms and hypervariable region I motifs, to test the genetic
      origins of the ethnically and linguistically heterogeneous Austro-Asiatic tribes
      of India. A comparative analysis of our results with the existing data suggests
      multiple origins of Austro-Asiatic tribes in India, and particularly the Asian
      and non-Asian origins of the Mon-Khmer and the Mundari populations. We also
      identified a novel subclade of haplogroup B in the Mon-Khmer Khasi tribes that
      distinguishes them from the Nicobarese, indicating two different waves of
      migration of the Mon-Khmer tribes in India.

PMID- 16788904
TI  - Smoking during pregnancy and components of stature in offspring.
AB  - The objective of this study was to examine the association between maternal
      smoking during pregnancy and offspring height and its components. The analysis
      was based on 6,340 white singletons born in 1991-1992 and enrolled in the Avon
      Longitudinal Study of Parents and Children (ALSPAC), who had maternal smoking
      data recorded for at least one trimester in pregnancy, and who had their height
      recorded at age 7.5. Smoking at any time in pregnancy was associated with a
      reduction in offspring height, trunk, and leg length, and the leg-to-trunk ratio,
      after adjustment for age and sex. After additional adjustment for maternal
      factors, social factors, and breastfeeding, associations with leg length and leg
      to-trunk ratio remained, with reductions of 0.25 cm (95% confidence interval,
      0.05-0.46 cm) in leg length and 0.30% (95% confidence interval, 0.03-0.57%) in
      leg-to-trunk ratio if the mother smoked. Findings were similar when the smoking
      data were analyzed separately for each trimester. Furthermore, in each trimester,
      the more a mother smoked, the greater the reduction in offspring height, leg
      length, and leg-to-trunk ratio. These dose-response relationships remained after
      adjustment for all potential confounders for leg length and leg-to-trunk ratio.
      Smoking at any time in pregnancy reduces offspring height and its components, and
      in particular leg length and leg-to-trunk ratio at age 7.5.

PMID- 16788905
TI  - Common set of genes regulates low-density lipoprotein size and obesity-related
      factors in Alaskan Eskimos: results from the GOCADAN study.
AB  - Increasing incidence of cardiovascular disease in traditionally low-risk Alaskan
      Eskimos is a cause for concern. The purpose of this study was to examine the
      genetic and environmental correlations of low-density lipoprotein (LDL)
      subfractions with obesity-related factors in Alaskan Eskimos, using data from the
      first 954 participants of the Genetics of Coronary Artery Disease in Alaska
      Natives Study. Estimates of genetic and environmental influence were calculated
      using a maximum likelihood variance component method implemented in SOLAR. Mean
      values of weight, body mass index (BMI), and waist were 73.4 +/- 0.5 kg, 27.6 +/-
      0.2 kg/m2, and 88.0 +/- 0.4 cm, respectively. LDL, and its small (LDL1), medium
      (LDL2), and large (LDL3) subfractions, had mean values of 115.8 +/- 1.2 mg/dl,
      8.3 +/- 0.4 mg/dl, 19.6 +/- 0.8 mg/dl, and 71.5 +/- 1.5 mg/dl, respectively.
      Bivariate analysis displayed significant genetic correlations between LDL
      subfractions and obesity-related factors: LDL1 with BMI (rhoG = 0.67, P < 0.05),
      waist (rhoG = 0.80, P < 0.001), and subscapular and tricep skinfolds (rhoG =
      0.93, P < 0.005, and rhoG = 0.78, P < 0.05, respectively); LDL2 with BMI (rhoG =
      0.52, P < 0.05), waist (rhoG = 0.46, P < 0.05), and tricep skinfold (rhoG = 0.60,
      P < 0.05); and mean LDL size with BMI (rhoG = -0.36), waist (rhoG = -0.42,), and
      subscapular and tricep skinfolds (rhoG = -0.44 and -0.43, respectively) (P <
      0.005). These results show that a common set of genes is influencing LDL size and
      obesity-related factors in Alaskan Eskimos.

PMID- 16788906
TI  - Gene flow in the Iberian Peninsula determined from Y-chromosome STR loci.
AB  - In this work, seven multiallelic short-tandem repeat (STR) loci from the
      nonrecombining region of the human Y-chromosome (DYS19, DYS389 I, DYS389 II,
      DYS390, DYS391, DYS392, and DYS393) were typed in a sample of residents in the
      Basque Country (RBAS). In all, 40 different Y-STR haplotypic combinations were
      identified, resulting in a value of haplotypic diversity of 0.979. Y-STR data
      compiled from previous works were used for studying Y-chromosome diversity in the
      Iberian Peninsula and for assessing the effects of migratory movements on the
      genetic background of the population living currently in territories
      traditionally occupied by native (autochthonous) Basques. An analysis of the
      spatial distribution of allelic frequencies of the Y-STRs revealed a geographic
      pattern characterized by variation gradients (frequency clines) oriented for the
      most part in the direction southwest-northeast. Accordingly, a neighbor-joining
      analysis showed a relative polarization between populations located in the
      northeast and center of the Iberian Peninsula, and the rest of the samples
      considered. The study sample (RBAS) occupied an intermediate position in the
      population tree between the autochthonous Basques (BASQ) and the remaining
      samples. Interestingly, the RBAS collection only showed genetic heterogeneity
      with that of native Basques (PhiST = 0.013, P < 0.05). Estimates of admixture
      proportions in the gene pool of RBAS indicated a high level of hybridization with
      Basque (56%) and non-Basque (44%) genes, which could explain the genetic
      differentiation observed between BASQ and RBAS.

PMID- 16788907
TI  - Temporally regulated delivery of VEGF in vitro and in vivo.
AB  - The exposure duration and tissue distribution will likely dictate the success of
      vascular endothelial growth factor (VEGF) in therapeutic angiogenesis. We
      hypothesized that these variables can be regulated via the manner in which the
      VEGF is incorporated into polymer constructs (formed with a gas foaming
      technique) used for its delivery. VEGF was incorporated directly into
      poly(lactide-co-glycolide) (PLG) scaffolds or pre-encapsulated in PLG
      microspheres used to fabricate scaffolds. Protein release kinetics and tissue
      distribution were determined using iodinated VEGF. VEGF was positioned
      predominantly adjacent to scaffold pores when incorporated directly and was
      released rapidly (40-60% in 5 days). Pre-encapsulation led to the VEGF being more
      deeply embedded and resulted in a delayed release. Alterations in polymer
      composition, scaffold size, and matrix composition generated minor variations in
      release kinetics. In vivo, the released VEGF generated local protein
      concentrations above 10 ng/mL at distances up to 2 cm from the implant site for
      the 21 days of the experiment, with negligible release into the systemic
      circulation, and significantly enhanced local angiogenesis. These data indicate
      that VEGF can be administered in a sustained and localized fashion in vivo, and
      the timing of VEGF delivery can be altered with the mechanism of incorporation
      into polymer scaffolds used for its delivery.

PMID- 16788908
TI  - Systematic QM/MM investigation of factors that affect the cytochrome P450
      catalyzed hydrogen abstraction of camphor.
AB  - The hydrogen abstraction reaction of camphor in cytochrome P450(cam) has been
      investigated in the native enzyme environment by combined quantum
      mechanical/molecular mechanical (QM/MM) calculations and in the gas phase by
      density functional calculations. This work has been motivated by contradictory
      published QM/MM results. In an attempt to pinpoint the origin of these
      discrepancies, we have systematically studied the factors that may affect the
      computed barriers, including the QM/MM setup, the optimization procedures, and
      the choice of QM region, basis set, and protonation states. It is found that the
      ChemShell and QSite programs used in the published QM/MM calculations yield
      similar results at given geometries, and that the discrepancies mainly arise from
      two technical issues (optimization protocols and initial system preparation) that
      need to be well controlled in QM/MM work. In the course of these systematic
      investigations, new mechanistic insights have been gained. The crystallographic
      water 903 placed near the oxo atom of Compound I lowers the hydrogen abstraction
      barrier by ca. 4 kcal/mol, and thus acts as a catalyst for this reaction. Spin
      density may appear at the A-propionate side chain of the heme if the carboxylate
      group is not properly screened, which might be expected to happen during protein
      dynamics, but not in static equilibrium situations. There is no clear correlation
      between the computed A-propionate spin density and the hydrogen abstraction
      barrier, and hence, no support for a previously proposed side-chain mediated
      transition state stabilization mechanism. Standard QM/MM optimizations yield an A
      propionate environment close to the X-ray structure only for protonated Asp297,
      and not for deprotonated Asp297, but the computed barriers are similar in both
      cases. An X-ray like A-propionate environment can also be obtained when
      deprotonated Asp297 is included in the QM region and His355 is singly protonated,
      but this Compound II-type species with a closed-shell porphyrin ring has a higher
      hydrogen abstraction barrier and should thus not be mechanistically relevant.

PMID- 16788909
TI  - Electronic structure of iron(II)-porphyrin nitroxyl complexes: molecular
      mechanism of fungal nitric oxide reductase (P450nor).
AB  - Density functional calculations are employed to investigate key intermediates of
      the catalytic cycle of fungal nitric oxide reductase (P450nor). The formal Fe(II)
      nitroxyl species Fe(II)--NO/(-) can principally exist in the two spin-states S =
      0 and S = 1. In the S = 0 case, a very covalent Fe--NO sigma bond is present,
      which leads to an electronic structure description that is actually intermediate
      between Fe(I)--NO and Fe(II)--NO(-). In contrast, the S = 1 case shows a ferrous
      Fe(II)--NO complex with the extra electron being stored in the pi system of the
      porphyrin ligand. Importantly, the Fe(II)--NO/(-) species are very basic. The
      electronic structures and spectroscopic properties of the corresponding N- and O
      protonated forms are very different, and unequivocally show that the Mb-HNO
      adduct (Mb-Myoglobin) prepared by farmer and coworkers is in fact N-protonated.
      The presence of an axial thiolate ligand enables a second protonation leading to
      the corresponding Fe(IV)--NHOH- species, which is identified with the
      catalytically active intermediate I of P450nor. This species reacts with a second
      molecule of NO by initial electron transfer from NO to Fe(IV) followed by
      addition of NO+ forming an N--N bond. This is accompanied by an energetically
      very favorable intramolecular proton transfer leading to the generation of a
      quite stable Fe(III)--N(OH)(NOH) complex. This way, the enzyme is able to produce
      dimerized HNO under very controlled conditions and to prevent loss of this ligand
      from Fe(III). The energetically disfavoured tautomer Fe(III)--N(OH2)(NO) is the
      catalytically productive species that spontaneously cleaves the N--OH2 bond
      forming N2O and H2O in a highly exergonic reaction.

PMID- 16788910
TI  - On the O2 binding of Fe-porphyrin, Fe-porphycene, and Fe-corrphycene complexes.
AB  - Based on our previous study for the O2 binding of the Fe-Por complex, this study
      investigates the O2 binding mechanism in the Fe-porphyrin isomers, Fe-porphycene
      (FePc), and Fe-corrphycene (FeCor) complexes. By calculating the potential energy
      surface of the O2 binding, the present study explains the reason for the dramatic
      increase of O2 affinities observed in the FePc complex. In the case of FeCor-O2,
      the O2 binding process includes the intersystem crossing from a triplet to
      singlet state, as in the FePor-O2 complex. However, FePc-O2 uses only a singlet
      surface. This is because the ground state of the FePc complex in the deoxy state
      is a triplet state, while those of FePor and FeCor are a quintet state. Such
      difference originates from character of the SOMO. We estimated an equilibrium
      constant for the O2 binding that reasonably reproduced the trend observed in the
      experiments.

PMID- 16788911
TI  - On the accuracy of density functional theory for iron-sulfur clusters.
AB  - A simple, yet powerful wave function manipulation method was introduced utilizing
      a generalized ionic fragment approach that allows for systematic mapping of the
      wave function space for multispin systems with antiferromagnetic coupling. The
      use of this method was demonstrated for developing ground state electronic wave
      function for [2Fe-2S] and [Mo-3Fe-4S] clusters. Using well-defined ionic wave
      functions for ferrous and ferric irons, sulfide, and thiolate fragments, the
      accuracy of various density functionals and basis sets including effective core
      potentials were evaluated on a [4Fe-4S] cluster by comparing the calculated
      geometric and electronic structures with crystallographic data and experimental
      atomic spin densities from X-ray absorption spectroscopy, respectively. We found
      that the most reasonable agreement for both geometry and atomic spin densities is
      obtained by a hybrid functional with 5% HF exchange and 95% density functional
      exchange supplemented with Perdew's 1986 correlation functional. The basis set
      seems to saturate only at the triple-zeta level with polarization and diffuse
      functions. Reasonably preoptimized structures can be obtained by employing
      computationally less expensive effective core potentials, such as the Stuttgart
      Dresden potential with a triple-zeta valence basis set. The extension of the
      described calibration methodology to other biologically important and more
      complex iron-sulfur clusters, such as hydrogenase H-cluster and nitrogenase FeMo
      co will follow.

PMID- 16788912
TI  - QM/MM modeling of compound I active species in cytochrome P450, cytochrome C
      peroxidase, and ascorbate peroxidase.
AB  - QM/MM calculations provide a means for predicting the electronic structure of the
      metal center in metalloproteins. Two heme peroxidases, Cytochrome c Peroxidase
      (CcP) and Ascorbate Peroxidase (APX), have a structurally very similar active
      site, yet have active intermediates with very different electronic structures. We
      review our recent QM/MM calculations on these systems, and present new
      computational data. Our results are in good agreement with experiment, and
      suggest that the difference in electronic structure is due to a large number of
      small differences in structure from one protein to another. We also discuss
      recent QM/MM calculations on the active species of cytochrome P450, in which a
      similar sensitivity of the electronic structure to the environment is found.
      However, this does not appear to explain different catalytic profiles of the
      different drug-metabolizing isoforms of this class of enzyme.

PMID- 16788913
TI  - Quantum chemistry applied to the mechanisms of transition metal containing
      enzymes -- cytochrome c oxidase, a particularly challenging case.
AB  - The Density functional theory (B3LYP) has been used to study the mechanisms of O-
      O bond cleavage and proton pumping in cytochrome c oxidase. To understand how the
      energy from the exergonic reduction of molecular oxygen is used to pump protons
      across the mitochondrial membrane, the energetics of all steps in the catalytic
      cycle have to be evaluated. For this purpose, models have to be designed that can
      accurately reproduce relative redox potentials and pKa values within the active
      site. The present study shows that it is possible to construct such models and to
      calculate energy profiles which, to a large extent, agree with experimental
      information. However, the energy profiles point out a problem with an unbalanced
      partitioning of the energy between the reductive and oxidative half cycles, which
      is in disagreement with the experimental observation that the proton pumping is
      evenly distributed between the two half cycles. A conclusion from the present
      study is, therefore, that something is probably still missing in the modeling of
      the active site.

PMID- 16788914
TI  - Prenatal sex ratios and expression of sexually dimorphic traits in three snake
      species.
AB  - Variation in intrauterine exposure to hormones associated with variation in the
      sex of litter mates has well-established and far-reaching effects on sexual
      development in some mammals. Research on this phenomenon in reptiles is scant,
      but suggests that lizards may follow the mammalian model whereas snakes may be
      affected differently. We examined sex-specific expression of four sexually
      dimorphic traits (tail length, head length, ventral scale count, swimming speed)
      in three species of snakes (Nerodia sipedon, Thamnophis sirtalis, T. sauritus)
      relative to litter sex ratios. We found little evidence that traits in either sex
      were masculinized or feminized in response to variation in litter sex ratio. The
      one significant result appeared best explained as a statistical artifact
      attributable to a single litter. Our results indicate that snakes are different
      from the one lizard studied to date. Unlike previous suggestions that prenatal
      hormonal mechanisms operate differently in snakes and lizards, however, the
      difference appears to be that development of sexually dimorphic traits in lizards
      is affected by litter sex ratios whereas in snakes it is not.

PMID- 16788915
TI  - Metabolic organization of the spotted ratfish, Hydrolagus colliei (Holocephali:
      Chimaeriformes): insight into the evolution of energy metabolism in the
      chondrichthyan fishes.
AB  - The metabolic organization of a holocephalan, the spotted ratfish (Hydrolagus
      colliei), was assessed using measurements of key enzymes of several metabolic
      pathways in four tissues and plasma concentrations of free amino acids (FAA) and
      non-esterified fatty acids (NEFA) to ascertain if the Holocephali differ
      metabolically from the Elasmobranchii since these groups diverged ca. 400 Mya.
      Activities of carnitine palmitoyl transferase indicate that fatty acid oxidation
      occurs in liver and kidney but not in heart or white muscle. This result mirrors
      the well-established absence of lipid oxidation in elasmobranch muscle, and more
      recent studies showing that elasmobranch kidney possesses a capacity for lipid
      oxidation. High activities in oxidative tissues of enzymes of ketone body
      metabolism, including D-beta-hydroxybutyrate dehydrogenase, indicate that, like
      elasmobranchs, ketone bodies are of central importance in spotted ratfish. Like
      many carnivorous fishes, enzyme activities demonstrate that amino acids are
      metabolically important, although the concentration of plasma FAA was relatively
      low. NEFA concentrations are lower than in teleosts, but higher than in most
      elasmobranchs and similar to that in some "primitive" ray-finned fishes. NEFA
      composition is comparable to other marine temperate fishes, including high levels
      of n-6 and especially n-3 polyunsaturated fatty acids. The metabolic organization
      of the spotted ratfish is similar to that of elasmobranchs: a reduced capacity
      for lipid oxidation in muscle, lower plasma NEFA levels, and an emphasis on
      ketone bodies as oxidative fuel. This metabolic strategy was likely present in
      the common chondrichthyan ancestor, and may be similar to the ancestral metabolic
      state of fishes.

PMID- 16788916
TI  - Aspartic proteinases in the digestive tract of marine decapod crustaceans.
AB  - Decapod crustaceans synthesize highly active proteolytic enzymes in the midgut
      gland and release at least a part of them into the stomach where they facilitate
      the first step in peptide hydrolysis. The most common proteinases in the gastric
      fluid characterized so far are serine proteinases, that is, trypsin and
      chymotrypsin. These enzymes show highest activities at neutral or slightly
      alkaline conditions. The presence of acid proteinases, as they prevail in
      vertebrates, has been discussed contradictorily yet in invertebrates. In this
      study, we show that acid aspartic proteinases appear in the gastric fluid of
      several decapods. Lobsters Homarus gammarus showed the highest activity with a
      maximum at pH 3. These activities were almost entirely inhibited by pepstatin A,
      which indicates a high share of aspartic proteinases. In other species (Panulirus
      interruptus, Cancer pagurus, Callinectes arcuatus and Callinectes bellicosus),
      proteolytic activities were present at acid conditions but were distinctly lower
      than in H. gammarus. Zymograms at pH 3 showed in each of the studied species at
      least one, but mostly two-four bands of activity. The apparent molecular weight
      of the enzymes ranged from 17.8 to 38.6 kDa. Two distinct bands were identified
      which were inhibited by pepstatin A. Acid aspartic proteinases may play an
      important role in the process of extracellular digestion in decapod crustaceans.
      Activities were significantly higher in clawed lobster than in spiny lobster and
      three species of brachyurans. Therefore, it may be suggested that the expression
      of acid proteinases is favored in certain groups and reduced in others.

PMID- 16788917
TI  - Log-Euclidean metrics for fast and simple calculus on diffusion tensors.
AB  - Diffusion tensor imaging (DT-MRI or DTI) is an emerging imaging modality whose
      importance has been growing considerably. However, the processing of this type of
      data (i.e., symmetric positive-definite matrices), called "tensors" here, has
      proved difficult in recent years. Usual Euclidean operations on matrices suffer
      from many defects on tensors, which have led to the use of many ad hoc methods.
      Recently, affine-invariant Riemannian metrics have been proposed as a rigorous
      and general framework in which these defects are corrected. These metrics have
      excellent theoretical properties and provide powerful processing tools, but also
      lead in practice to complex and slow algorithms. To remedy this limitation, a new
      family of Riemannian metrics called Log-Euclidean is proposed in this article.
      They also have excellent theoretical properties and yield similar results in
      practice, but with much simpler and faster computations. This new approach is
      based on a novel vector space structure for tensors. In this framework,
      Riemannian computations can be converted into Euclidean ones once tensors have
      been transformed into their matrix logarithms. Theoretical aspects are presented
      and the Euclidean, affine-invariant, and Log-Euclidean frameworks are compared
      experimentally. The comparison is carried out on interpolation and regularization
      tasks on synthetic and clinical 3D DTI data.

PMID- 16788918
TI  - Multicell tumor spheroids in photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVES: Multicell spheroids (MCSs) represent a simple in vitro
      system ideally suited for studying the effects of a wide variety of
      investigational treatments including photodynamic therapy (PDT). STUDY
      DESIGN/MATERIALS AND METHODS: In the first section of this review study, an
      overview of the current literature on MCS in PDT will be presented. Knowledge of
      basic PDT parameters has been gained from numerous MCS studies, in particular,
      the mechanisms of sensitizer photobleaching have been elucidated. MCSs have also
      proven useful for the study of complex PDT treatment regimens including multiple
      treatments and combined therapies involving PDT and ionizing radiation or
      hyperthermia. The purpose of the second part of this review is to present results
      from recent studies in our laboratory aimed at developing MCS models suitable for
      investigating tumor cell invasion and angiogenesis-processes characteristic of
      high-grade gliomas. RESULTS AND CONCLUSION: To that end, progress has recently
      been made to develop a more accurate in vivo brain tumor model consisting of
      biopsy-derived human tumor spheroids implanted into the brains of immunodeficient
      rats. Finally, recent work suggests that computer simulations may prove useful to
      describe the growth of MCS and predict the effects of investigational therapies
      including PDT. Such in silico models have made a number of counterintuitive
      predictions that have been verified in vitro and, as such, could guide the
      development of improved therapeutics.

PMID- 16788919
TI  - Basic and clinical research on photodynamic therapy at Tokyo Medical University
      Hospital.
AB  - BACKGROUND AND OBJECTIVES: We have been engaged in basic and clinical research on
      photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25
      years. STUDY DESIGN/MATERIALS AND METHODS: PDT for 264 centrally located early
      stage lung cancer lesions yielded an initial complete response (CR) rate of
      84.8%. PDT is now becoming a standard option for centrally located stage 0
      (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for
      elderly patients in poor physical condition. RESULTS: Recent results of
      interstitial PDT for peripheral-type lung cancers suggest that it may be a
      promising local curative treatment modality for lesions less than 1.0 cm in
      diameter. CONCLUSIONS: In this article, we introduce our recent clinical trials
      of PDT for lung cancers (both central and peripheral), and new techniques of PDD
      in sentinel node navigation biopsy for breast cancers. Moreover, we introduce
      basic research on cancers and infectious diseases in order to expand the clinical
      applications of PDT.

PMID- 16788920
TI  - Local physiological changes during photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVE: Herein an overview is provided of the causes,
      consequences, and significance of photodynamic therapy (PDT)-mediated effects on
      tumor oxygenation and blood flow during illumination. STUDY DESIGN/MATERIALS AND
      METHODS: Techniques particularly valuable to this research have included tissue
      oxygen tension measurement by the Eppendorf pO2 Histograph; spatial
      quantification of hypoxia by EF3 and EF5; and tissue oxygenation/blood flow
      monitoring by diffuse reflectance/correlation spectroscopy. RESULTS: Severe
      hypoxia was measured in vivo during PDT and is shown to be a consequence of
      photochemical oxygen consumption and/or compromised vascular perfusion. Oxygen
      depletion can be controlled by treatment regimen, occurs in a spatially-definable
      pattern, and is therapy-limiting. PDT-induced changes in tumor oxygenation during
      illumination are correlated with outcome. In PDT-treated tissues, blood flow also
      is determined by treatment regimen and correlates with treatment response.
      CONCLUSIONS: Photodynamic therapy creates distinct, measurable changes in tumor
      oxygen and blood flow during illumination. These physiological changes may
      ultimately affect treatment efficacy.

PMID- 16788921
TI  - Photodynamic therapy and anti-tumor immunity.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) efficacy appears to be
      enhanced in the presence of an intact immune system and PDT has been shown to
      augment anti-tumor immunity. The mechanisms leading to the enhancement of the
      host immune response to tumor are unclear. Anti-tumor immunity depends upon the
      presence of activated antigen presenting cells (APCs). These cells are activated
      by their recognition of components released by pathogens, viruses, dead cells,
      and the presence of pro-inflammatory mediators. Activated APCs stimulate the
      generation of cytokine secreting effector cells. Therefore, we have hypothesized
      that PDT generated inflammatory mediators and components released from tumor
      cells killed by PDT results in the activation of APCs capable of stimulating
      effector T-cell proliferation and cytokine secretion. STUDY DESIGN/MATERIALS AND
      METHODS: To determine the effect of PDT on APCs, tumor draining lymph nodes
      (TDLNs) of EMT6 or Colo 26 tumor bearing mice were isolated 24 hours after
      Photofrin-PDT and flow cytometry was used to detect the presence of APCs
      secreting the T cells stimulatory cytokine, IL-12. APCs were also isolated from
      TDLNs and used to stimulate T-cell proliferation and secretion of interferon
      gamma (IFN-gamma). RESULTS: PDT results in an increase in IL-12 expressing APCs
      in the TDLN. This increase was accompanied by an increase in the ability of APCs
      isolated from TDLNs of PDT-treated mice to stimulate T-cell proliferation and T
      cell secretion of IFN-gamma. CONCLUSIONS: Our results indicate that APCs isolated
      from PDT-treated mice exhibit an enhanced ability to stimulate T-cell
      proliferation and IFN-gamma secretion, suggesting that PDT results in increased
      APC activity.

PMID- 16788923
TI  - Advances in photodynamic therapy for the treatment of head and neck cancers.
AB  - Photodynamic therapy (PDT) is an FDA-approved minimally invasive medical
      treatment modality that utilizes light in the presence of oxygen to activate
      photosensitizing agents that are relatively selectively concentrated in abnormal
      or neoplastic cells resulting in cell death. At the present time, PDT has been
      approved for clinical treatment in the United States, European Union, Canada,
      Russia, and Japan. In the United States, US Food and Drug administration approval
      has been given for the use of PDT in the treatment of Barrett's esophagus,
      obstructing esophageal carcinoma and early and obstructing tracheobronchial
      carcinoma using the photosensitizer Photofrin; actinic keratosis using the
      photosensitizer Levulan (aminolevulinic acid); and macular degeneration using the
      photosensitizer BPD. In the EU the above noted indications have also been
      approved in addition to the treatment of early head and neck cancers and
      palliative treatment of head and neck cancer using the photosensitizer Foscan;
      and treatment of basal and squamous cell skin cancers using the photosensitizer
      Metvix.

PMID- 16788924
TI  - Role of photodynamic therapy in unresectable esophageal and lung cancer.
AB  - The incidence of esophageal cancer has increased dramatically in the Western
      population in the last two decades. Many of these patients tend to present late
      in the disease course with symptoms of dysphagia and malnutrition. Thus a
      majority of patients at presentation may require palliation of their symptoms.
      Lung cancer is the most common cause of cancer related mortality in the United
      States. Similar to esophageal cancer, many patients present in advanced stages
      where surgical resection for cure may not be an option. Endobronchial obstruction
      from both primary and metastatic neoplasm causes significant morbidity. The
      modalities, which are currently available for palliation of symptoms include
      surgery, photodynamic therapy, dilation, external beam radiation, stents, Nd:YAG
      laser therapy, and brachytherapy. Each of these modalities has their specific
      advantages and drawbacks. In this article, we discuss the role of photodynamic
      therapy in the palliation of esophageal and lung cancer.

PMID- 16788925
TI  - Control of pesticide residues by liquid chromatography-mass spectrometry to
      ensure food safety.
AB  - Liquid chromatography-mass spectrometry (LC-MS) has become an invaluable
      technique for the control of pesticide residues to ensure food safety. After an
      introduction about the regulations that highlights its importance to meet the
      official requirements on analytical performance, the different mass spectrometers
      used in this field of research, as well as the LC-MS interfaces and the
      difficulties associated with quantitative LC-MS determination, are discussed. The
      ability to use practical data for quantifying pesticides together with the option
      of obtaining structural information to identify target and non-target parent
      compounds and metabolites are discussed. Special attention is paid to the impact
      of sample preparation and chromatography on the ionization efficiency of
      pesticides from food. The last section is devoted to applications from a food
      safety point of view. (c) 2006 Wiley Periodicals, Inc.

PMID- 16788926
TI  - Photodynamic therapy of brain tumors--a work in progress.
AB  - BACKGROUND AND OBJECTIVES: PDT has been used in the treatment of malignant brain
      tumors. This communication updates our series of unselected malignant gliomas
      treated with Photofrin-PDT. STUDY DESIGN AND METHODS: We examined the records of
      112 patients with malignant gliomas, metastatic brain tumors and meningiomas
      treated with Photofrin-PDT at St. Michael's Hospital, Toronto. These patients
      were treated prior to the onset of ongoing randomized trials in Photofrin PDT or
      had pathology that excluded them from such trials. RESULTS: The overall post-PDT
      survival of 96 patients with supratentorial gliomas was 42 weeks, with a 40 and
      22% 1- and 2-year survival, respectively. The greater the degree of
      oligodendroglial involvement the longer was the survival. Seventy-five percent of
      patients had no significant post-operative complications. CONCLUSIONS: Photofrin
      PDT was safe. However, higher light doses than were used in these patients may be
      required for improved responses.

PMID- 16788927
TI  - Porfimer sodium photodynamic therapy for management of Barrett's esophagus with
      high-grade dysplasia.
AB  - Porfimer sodium photodynamic therapy (ps-PDT) for Barrett's esophagus is a
      powerful endoscopic treatment that can eliminate high-grade dysplasia (HGD) and
      Barrett's mucosa and reduce the risk of development of cancer in these patients.
      Ps-PDT typically results in destruction of Barrett's esophagus in the majority of
      the treated area. However, residual small island of Barrett's mucosa may persist
      after PDT. Therefore, adjuvant thermal ablation should be available during follow
      up endoscopies for ablation of residual islands of Barrett's mucosa. PDT should
      be applied concurrent with effective proton pump inhibitor therapy. This article
      provides a practical guide for application of porfimer sodium balloon PDT for
      management of Barrett's esophagus with HGD. Recommendations are provided for
      patient selection and screening, delivery of PDT to include light dosimetry,
      methodology for follow-up endoscopies, as well as discussing the potential side
      effects and complications.

PMID- 16788928
TI  - A dose ranging study of photodynamic therapy with porfimer sodium (Photofrin) for
      treatment of basal cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: While basal cell carcinoma (BCC) is effectively
      treated by several methods, many patients with numerous or frequently occurring
      lesions seek alternatives that can treat multiple cancers, with improved cosmetic
      outcome. PDT for esophageal and lung carcinomas is approved at a porfimer sodium
      (Photofrin) dose of 2 mg/kg, but lower doses increase selectivity and decrease
      both cutaneous phototoxicity and cost. We evaluated low doses of porfimer sodium
      PDT for treatment of multiple BCC. MATERIALS AND METHODS: Seventy-seven patients
      with 2,041 BCC were injected with 0.75, 0.875, or 1.0 mg/kg porfimer sodium and
      treated 2 days later with 630-nm light. Clinical responses were determined at 6
      months, then periodically to 5 years. RESULTS: Increasing porfimer sodium dose
      increased complete responses (CR), with initial CR rates of 72.7% (66-78%, 95%
      CI), 79.9% (73-86%, 95% CI), and 92.2% (91-93%, 95% CI), albeit with some lower
      selectivity at the highest dose. At 1 mg/kg, 5-year recurrence rates were 28% (21
      35%, 95% CI) and 15% (11-18%, 95% CI) for sporadic and nevoid basal cell
      carcinoma syndrome (NBCCS) lesions, respectively. CONCLUSIONS: This is the
      largest dose-ranging study of porfimer sodium, and the largest number of lesions
      treated in a single study. We found that with 1 mg/kg porfimer sodium, PDT can be
      a selective and durable treatment for sporadic and NBCCS-associated BCC.

PMID- 16788929
TI  - Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate
      cancer.
AB  - BACKGROUND AND OBJECTIVES: Interstitial photodynamic therapy (PDT) is an emerging
      modality for the treatment of solid organ disease. Our group at the University of
      Pennsylvania has performed extensive studies that demonstrate the feasibility of
      interstitial PDT for prostate cancer. Our preclinical and clinical experience is
      herein detailed. STUDY DESIGN/MATERIALS AND METHODS: We have treated 16 canines
      in preclinical studies, and 16 human subjects in a Phase I study, using motexafin
      lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light
      fluence, drug level and oxygen distribution for these patients were performed.
      RESULTS: We demonstrate the safe and comprehensive treatment of the prostate
      using PDT. However, there is significant variability in the dose distribution and
      the subsequent tissue necrosis throughout the prostate. CONCLUSIONS: PDT is an
      attractive option for the treatment of prostate adenocarcinoma. However, the
      observed variation in PDT dose distribution translates into uncertain therapeutic
      reproducibility. Our future focus will be on the development of an integrated
      system that is able to both detect and compensate for dose variations in real
      time, in order to deliver a consistent overall PDT dose distribution.

PMID- 16788930
TI  - Nature: a rich source for developing multifunctional agents. Tumor-imaging and
      photodynamic therapy.
AB  - The purpose of this review is to call attention in the use of chlorophyll-a and
      bacteriochlorophyll-a to develop more than 600 photosensitizers (lambda (max) 660
      nm-800 nm) during the last 15 years (1990-2005) at the Photodynamic Therapy
      Center, Roswell Park Cancer Institute, Buffalo. This article mainly includes the
      chemistry, preclinical results, and brief clinical data of some of the most
      effective photosensitizers. The utility of the tumor-avid photosensitizers in
      developing multimodality agents (imaging and therapy) is also presented.

PMID- 16788932
TI  - Endobronchial photodynamic therapy for lung cancer.
AB  - BACKGROUND AND OBJECTIVE: Endobronchial photodynamic therapy (PDT) is a minimally
      invasive technique for the palliation of major airway obstruction from lung
      cancer, and for the treatment of endobronchial microinvasive lung cancer. STUDY
      DESIGN: Results of reported clinical trials were compared, and the author's
      preliminary results with second generation photosensitizers were also reviewed.
      RESULTS: A review of the clinical experience with endobronchial PDT is provided.
      Potential advantages of PDT include the duration of palliation achieved through
      the delayed cellular effects of PDT within tumor. Side-effects from FDA-approved
      photosensitizer (Photofrin, Porfimer sodium, Axcan Scandipharm, Montreal, Quebec)
      include skin photosensitivity. HPPH (2-[1-hexyloxyethyl]-2 devinyl
      pyropheophorbide) is an example of a second-generation photosensitize that shows
      promise in the treatment of lung cancer, and appears to be free from significant
      skin photosensitivity. CONCLUSION: PDT is an effective tool for the palliation of
      endobronchial lung cancers which obstruct the central airways and is also
      effective for the treatment of central microinvasive carcinoma and carcinoma in
      situ of the central airways.

PMID- 16788933
TI  - Clinical and research applications of photodynamic therapy in dermatology:
      experience of the Scottish PDT Centre.
AB  - BACKGROUND AND OBJECTIVES: The Scottish PDT Centre has carried out 3,442
      treatments on 762 patients with superficial skin lesions, especially superficial
      basal cell carcinoma (sBCC), Bowen's disease (BD) and actinic keratosis (AK).
      STUDY DESIGN MATERIALS AND METHODS: The article reviews our experience of various
      light sources and associated dosimetry; thereafter we discuss clinical outcome
      followed by some of our research studies in clinically important areas. RESULTS:
      We show that improved dosimetry is required to ensure an optimal light dose is
      delivered to the tumour. We have shown that photosensitizers and proteins
      interact in such a way that their photophysical and photochemical properties are
      modified. We have also demonstrated the presence of DNA strand breaks with two
      different photosensitizers, but there is no evidence that PDT is significantly
      mutagenic in clinical practice. CONCLUSIONS: In our experience, topical PDT is
      generally well tolerated and is an effective treatment of sBCC, BD, AK, field
      change and lesions at sites of poor healing.

PMID- 16788934
TI  - Photodynamic therapy in the treatment of microbial infections: basic principles
      and perspective applications.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) appears to be endowed with
      several favorable features for the treatment of infections originated by
      microbial pathogens, including a broad spectrum of action, the efficient
      inactivation of antibiotic-resistant strains, the low mutagenic potential, and
      the lack of selection of photoresistant microbial cells. Therefore, intensive
      studies are being pursued in order to define the scope and field of application
      of this approach. RESULTS: Optimal cytocidal activity against a large variety of
      bacterial, fungal, and protozoan pathogens has been found to be typical of
      photosensitizers that are positively charged at physiological pH values (e.g.,
      for the presence of quaternarized amino groups or the association with polylysine
      moieties) and are characterized by a moderate hydrophobicity (n-octanol/water
      partition coefficient around 10). These photosensitizers in a micromolar
      concentration can induce a >4-5 log decrease in the microbial population after
      incubation times as short as 5-10 minutes and irradiation under mild experimental
      conditions, such as fluence-rates around 50 mW/cm2 and irradiation times shorter
      than 15 minutes. CONCLUSIONS: PDT appears to represent an efficacious alternative
      modality for the treatment of localized microbial infections through the in situ
      application of the photosensitizer followed by irradiation of the photosensitizer
      loaded infected area. Proposed clinical fields of interest of antimicrobial PDT
      include the treatment of chronic ulcers, infected burns, acne vulgaris, and a
      variety of oral infections.

PMID- 16788935
TI  - Diagnosis of sarcoma by core biopsy.

PMID- 16788936
TI  - Prognostic significance of CEA levels and detection of CEA mRNA in draining
      venous blood in patients with colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: The aims of this study were to determine
      carcinoembryonic antigen (CEA) levels and incidence of tumor cells using the RT
      PCR technique in draining venous blood of patients with colorectal cancer,
      correlate the results with various histopathologic factors and determine their
      significance as prognostic factors. METHODS: From 1995 to 2000, 108 patients with
      adenocarcinoma of the colon or rectum, underwent curative surgery and enrolled in
      this prospective study. RESULTS: The 5-year survival group had significantly
      lower portal CEA levels compared to the hepatic metastasis outcome group. CEA
      mRNA was positive in the draining venous blood from 12 (11.1%) out of 108
      patients included in the study. The rate of positive tumor cell detection in
      portal blood was significantly higher in the hepatic metastasis outcome group
      than in the 5-year survival and recurrence group. The proportion of patients with
      portal CEA > or =5 ng/ml was greater in patients with higher stage than in
      patients with lower stage. CONCLUSIONS: Positive CEA mRNA in draining venous
      blood predicted hepatic metastases and local recurrence with accuracy over 80%
      but with low sensitivity of 30% and 9%, respectively. Moreover, CEA level was a
      sensitive indicator in hepatic metastases as sensitivity was 95% and a specific
      indicator in predicting 5-year survival with specificity 84%.

PMID- 16788937
TI  - Symmetrization reduction mammaplasty combined with sentinel node biopsy in
      patients operated for contralateral breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Occult invasive cancer found in reduction mammaplasty
      specimen in the contralateral breast in breast cancer patients requires axillary
      lymph node dissection (ALND) to assess the lymph node status. Routine Sentinel
      node (SN) biopsy in these patients may avoid secondary ALND when an occult cancer
      is found and the SN is negative in the permanent histological examination.
      METHODS: One hundred sixty-nine breast cancer patients underwent contralateral
      reduction mammaplasty for symmetrization and with SN biopsy of the non-cancer
      breast. SN mapping was done using a vital blue dye alone (n = 136) or in
      combination with a radiocolloid (n = 33). RESULTS: A mean number of 1.4 SNs
      (range 1-3 SNs) was identified in 158 of 169 patients (identification rate
      93.5%). One of 158 patients revealed a positive SN but no tumor was found in the
      reduction mammaplasty/mastectomy specimen, whereas the SN was negative in 157
      patients. Histological examination of the 169 reduction mammaplasty specimen
      revealed 5 occult invasive cancers and 4 patients with high grade DCIS but due to
      a negative SN biopsy the patients were spared a secondary ALND. CONCLUSION: The
      small number of patients with occult contralateral cancers may not warrant
      routine SN mapping in patients scheduled for contralateral reduction mammaplasty.

PMID- 16788938
TI  - Prognostic factors for patients with node-negative gastric cancer: Can extended
      lymph node dissection have a survival benefit?
AB  - BACKGROUND AND OBJECTIVES: For the patients with node-negative gastric cancer,
      there is no agreement on which clinicopathological factors influence the final
      results except T stage. The aim of this study was to investigate the prognostic
      factors, and to reveal whether the extent of lymph node dissection is associated
      with survival benefit for these patients. METHODS: Clinicopathological data of
      506 patients with node-negative gastric cancer were studied. We divided the
      patients into D1 and D2 groups and carried out univariate and multivariate
      survival analyses. RESULTS: On the univariate analysis, the factors influencing
      survival were age, tumor size, Borrmann type, resection type, and the T stage.
      However, multivariate analysis with the Cox proportional hazard model disclosed
      age and the T stage to be significant variables. The extent of lymphadenectomy
      was revealed to be the independent prognostic factors for survival only for the
      patients with T3 stage. CONCLUSIONS: For the patients with clinically node
      negative gastric cancer, an extended D2 lymph node dissection for the patients
      with T1 and T2 stage has no survival benefits. Although it might have some
      benefit for T3 stage by multivariate analysis, we should ascertain its value
      through a large randomized prospective study.

PMID- 16788939
TI  - Accurate diagnosis of musculoskeletal lesions by core needle biopsy.
AB  - BACKGROUND: Percutaneous needle biopsy has many advantages over open biopsy in
      the treatment of neoplasms. However, the accuracy of needle biopsy in the
      diagnosis of musculoskeletal lesions has not yet been established. Here, we
      evaluate the accuracy and limitations of the procedure for musculoskeletal
      lesions. METHODS: The diagnoses of 163 needle biopsies (bone, 91; soft tissue,
      72) performed on 157 consecutive patients using a Jamshidi needle or an Ostycut
      needle for bone lesions, or a Tru-cut needle for soft tissue lesions were
      compared with the final diagnoses made by open biopsy and/or a definitive
      operation. RESULTS: One hundred forty-three specimens (88%) were determined to be
      adequate for histological examination. Obtaining undamaged cores from very hard
      bony lesions or sclerotic cyst walls proved difficult. A pathologist with
      experience in musculoskeletal lesions was able to differentiate malignant tumors
      from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive
      at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores
      were obtained. Differentiating a well-differentiated liposarcoma from a benign
      lipoma and inflammatory lesions from benign tumorous conditions, was difficult.
      The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no
      morbidity related to the procedure. CONCLUSION: The results indicate that needle
      biopsy is safe and accurate for diagnosing musculoskeletal lesions.

PMID- 16788940
TI  - Radical reoperation for invasive cervical cancer found in simple hysterectomy.
AB  - OBJECTIVE: To evaluate the patients with invasive cervical cancer found in simple
      hysterectomy and who were subjected to radical parametrectomy and upper
      vaginectomy with therapeutic lymphadenectomy. METHODS: Twenty-seven patients who
      underwent the radical parametrectomy and upper vaginectomy with therapeutic
      lymphadenectomy procedure from 1986 to 2004 were retrospectively reviewed.
      RESULTS: The mean age at the time of diagnosis was 49.85 (range 38-72). The
      histopathological diagnoses were SCC, adenocarcinoma, adenosquamous carcinoma,
      endometroid carcinoma, and anaplastic carcinoma in 70.4%, 11.4%, 7.4%, 7.4%, and
      3.7% of patients, respectively. Operative complications occurred in only five
      patients (18.5%). Following radical surgery, residual disease was found in 10
      patients (37.03%). The lymph node involvement rate was 22.2% (6 patients). The
      recurrence rate was 7.4% (2 of 27 patients). The overall disease-free survival
      rate was 88.67%. The overall survival rate was 88.89%; it was significantly lower
      in the presence of the following factors: anaplastic carcinoma, vaginal apex
      metastasis, and pelvic lymph node metastasis. CONCLUSION: This series suggests
      the excellent overall survival of patients that underwent radical surgery. We
      recommend the surgical treatment of such selected patients in experienced centers
      only with expert surgeons and primary adjuvant radiotherapy may be recommended in
      selected patients.

PMID- 16788941
TI  - The incidence of hyperthyroidism in patients with thyroid cancer in an area of
      iodine deficiency.
AB  - BACKGROUND: The incidence of hyperthyroidism among thyroid malignancy varies
      greatly depending on the geographical area and iodine intake. The aim of the
      study was to evaluate the association of hyperthyroidism and thyroid cancer (TC)
      in an iodine deficient area. PATIENTS AND METHODS: Medical records of 422
      patients who underwent operation for TC between 1992 and 2000 in Ankara Oncology
      Hospital were reviewed. The characteristics of TC patients with hyperthyroidism
      were analyzed in respect to gender, age, histopathological type, thyroid function
      status, tumor size, extrathyroidal invasion, local recurrences, distant
      metastasis, AMES and MACIS scoring. RESULTS: In the present patient series, among
      422 patients with TC, hyperthyroidism was found in 12 patients (2.8%). None of
      the patients had Graves' disease. Of 12 patients with hyperthyroidism, 9 patients
      had papillary carcinoma, 1 patient had follicular carcinoma and 2 patients had
      follicular variant of papillary carcinoma. The tumor was in the active nodule in
      5 patients. CONCLUSION: The existence of hyperthyroidism among patients with
      differentiated TC is a clinical entity. Patients with hyperthyroidism and nodules
      require a careful approach in order to establish or exclude the possibility of TC
      especially in formerly iodine deficient areas.

PMID- 16788942
TI  - Solitary fibrous tumors of the pleura: Immunohistochemical analysis and
      evaluation of prognostic factors after surgical treatment.
AB  - BACKGROUND AND OBJECTIVES: Solitary fibrous tumors of the pleura (SFTP) are rare
      neoplasms with unusual histological and clinical features. Although surgery is
      the treatment of choice for SFTP, tumor recurrence may occur after complete
      resection, even in tumors with benign histological features. The aim of the study
      was to identify the clinical and pathological features of SFTP that are
      associated with a higher risk of recurrence after surgical treatment. METHODS:
      From May 1995 to September 2002, 18 patients (10 female, 8 male; mean age 58
      years) with SFTP underwent complete surgical treatment at our department. Mean
      follow-up was 61 months. Mean tumor size was 10 cm. The tumors were pedunculated
      in 10 patients and sessile in 8. Histological features were benign in 16 patients
      and malignant in 2. RESULTS: Five-year disease-free survival was 80%. A higher
      incidence of tumor recurrence was observed when SFTP originated from the parietal
      pleura, had malignant histological features and a lower expression of
      progesterone receptors (P < 0.05). CONCLUSIONS: Clinical and pathological
      characteristics, such as malignant histology, sessile morphology, and a lower
      expression of progesterone receptors identify SFTP with a higher risk of
      recurrence after surgery, and which thus require strict follow-up.

PMID- 16788943
TI  - Prognostic impact of orotate phosphoribosyl transferase activity in resectable
      colorectal cancers treated by 5-fluorouracil-based adjuvant chemotherapy.
AB  - BACKGROUND AND OBJECTIVES: Phosphoribosylation of 5-fluorouracil (5-FU) is an
      essential step which leads to tumor growth inhibition and orotate phosphoribosyl
      transferase (OPRT) is the main enzyme that involves in this conversion of 5-FU to
      5-fluorouridine monophosphate. This retrospective study was aimed to evaluate the
      correlation between tumor OPRT activity and the clinical outcome in colorectal
      cancer (CRC) patients treated by oral 5-FU-based adjuvant chemotherapy. METHODS:
      Surgical specimen was obtained from resectable 124 CRC patients who were
      subsequently treated by oral 5-FU-based adjuvant chemotherapy. OPRT activity in
      the extract of tumor tissue was enzymatically determined. The cut-off value of
      intratumor OPRT activity against disease free survival was determined by maximal
      chi2 method. The disease free survival and overall survival in each group were
      calculated using the Kaplan-Meier method. RESULTS: Patients were divided into two
      groups by determined cut-off value of intratumor OPRT (0.147 nmol/min/mg protein)
      (high group: n = 102, low group: n = 22). Five-year DFS (P = 0.035) and OS (P =
      0.020) were significantly better for high OPRT group. CONCLUSIONS: This study
      demonstrated that an assay of tumor OPRT contributes to the determination of 5-FU
      based adjuvant chemotherapy outcome and application in clinical practice should
      be included in tumor analysis prior to 5-FU-based adjuvant chemotherapy.

PMID- 16788944
TI  - Lack of activated Smad2 in transforming growth factor-beta signaling is an
      unfavorable prognostic factor in patients with esophageal squamous cell
      carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Transforming growth factor-beta (TGF-beta) regulates
      cell growth in various cells, and inactivation of the TGF-beta-signaling pathway
      contributes to tumor progression. In this study, we investigated the expression
      of Smad2 and Smad3, which are specific intracellular mediators of TGF-beta
      signaling. We also examined the relationship between the expression levels of
      activated Smad2 by TGF-beta and clinicopathologic characteristics of patients
      with esophageal squamous cell carcinoma (SCC). METHODS: Immunohistochemical
      staining with anti-phosphorylated Smad2 (P-Smad2) polyclonal antibody, anti-Smad2
      monoclonal antibody, and anti-Smad3 polyclonal antibody was performed on surgical
      specimens obtained from 80 patients with esophageal SCC. RESULTS: Our data
      indicated that a low level of P-Smad2, as detected immunohistologically,
      correlated with lymph node metastasis (P = 0.0002), distant metastasis (P =
      0.0338), pathologic stage (P = 0.0093), and poor survival rate (P = 0.0246). All
      patients without positive Smad2 immunostaining were included among those without
      positive P-Smad2 immunostaining. There was no significant correlation between
      expression of Smad2 or Smad3 and clinicopathologic characteristics. CONCLUSIONS:
      We demonstrated that a lack of Smad2-P appears to be correlated with tumor
      development and poor prognosis in patients with esophageal SCC.

PMID- 16788945
TI  - New method for prevention of bile leakage after hepatic resection.
AB  - BACKGROUND: The usefulness of fibrin glue and bioabsorbable polyglicolic acid
      (PGA) felt to prevent the bile leakage was studied. METHODS: Eighty-eight
      patients who underwent hepatic resection without biliary reconstruction from 2001
      through 2005 were studied. We divided 88 patients into 37 patients of Group A
      (who underwent hepatic resection between January 2001 and March 2003) and 51
      patients of Group B (who underwent hepatic resection between April 2003 and
      January 2005). The fibrin glue was applied to the excision site of remnant liver
      in the patients of Group A. On the other hand, the fibrin glue and bioabsorbable
      PGA sheet were applied in the patients of Group B. RESULTS: In Group A, the post
      operative bile leakage occurred in 3 of 37 patients (8.1%). The post-operative
      bleeding occurred in 1 of 37 patients (2.7%). And the post-operative wound
      infection occurred in 4 patients (10.8%). In Group B, no post-operative bile
      leakage and bleeding were observed in 51 patients. And the post-operative wound
      infection occurred in 3 patients (5.9%). The difference between Groups A and B in
      the rate of bile leakage was statistically significant. CONCLUSIONS: The
      combination of fibrin glue and bioabsorbable PGA felt was extremely favorable for
      prevention of bile leakage after hepatic resection.

PMID- 16788946
TI  - Esophageal mucosal stripping for palliation of dysphagia in advanced carcinoma of
      lower third esophagus diagnosed at laparotomy.
AB  - We report our novel technique, as a palliative procedure for carcinoma of the
      lower third esophagus, of stripping the mucosa of the esophagus with enbloc
      resection of cancer of the lower third esophagus with gastric pull up and
      cervical hand sewn esophagogastric anastomosis. This was undertaken primarily for
      the relief of dysphagia in locally advanced/metastatic cancer diagnosed at
      laparotomy. The technique has distinct advantages of being simpler, economical
      with minimal morbidity.

PMID- 16788947
TI  - Submucosal resection of giant gastric lipoma.

PMID- 16788948
TI  - Biology of colorectal liver metastases: A review.
AB  - Metastatic growth is a selective, non-random process, which in the case of
      colorectal cancer, frequently occurs in the liver and is the major cause of
      cancer related death in these patients. This review summarises attempts to find
      biological and molecular markers of metastasis and their role in establishment of
      secondary tumours. Recent evidence suggests that liver metastases are
      phenotypically different to the primary from which they were derived and thus
      represent a separate disease entity.

PMID- 16788949
TI  - Retroperitoneal sarcomas: Combined-modality treatment approaches.
AB  - Retroperitoneal sarcomas (RPS) are rare tumors, accounting for approximately 15%
      of soft tissue sarcomas. Surgical resection of localized tumors with gross and
      microscopically negative margins remains the standard of care. However, because
      RPS are frequently large and locally advanced, resections are often incomplete,
      resulting in local recurrence. Investigators are evaluating combined-modality
      therapies to improve local control and disease-specific survival. This review
      outlines current concepts and evolving treatment strategies in the diagnosis,
      staging, and management of RPS.

PMID- 16788950
TI  - The effect of intron location on the splicing of BmKK2 in 293T cells.
AB  - Previously reported results showed that the BmKK2's intron could be recognized
      and spliced in cultured HEK 293T cells. At the same time, a cryptic splicing site
      of BmKK2 gene was found in the second exon. Moreover, replacing BmKK2's intron
      with BmP03's intron (an artificial BmKK2-BmP03 mosaic gene) did not affect the
      intron's recognition and splicing, but increased the expression level of the
      toxin-GFP fusion protein (Cao et al., J Biochem Mol Toxicol 2006;20:1-6). In this
      investigation, the BmKK2's intron with 79 nucleotides length was artificially
      shifted from the 49th nt (the 17th Gly codon between the first base and the
      second base) to the 100th nt (the 34th Gly codon between the first base and the
      second base). Based on the constructed intron-splicing system, the results of RT
      PCR and the western blotting analysis showed that the BmKK2's shifted-intron
      (named BmKK2-s) was not recognized and spliced correctly, but the cryptic
      splicing site of BmKK2 gene was still spliced in the second exon, which possibly
      indicated that locations of introns were very important to the recognition and
      splicing of introns, and splicing of introns was very much associated with the
      corresponding upstream and downstream exons. This result possibly provides
      evidence for splice-site recognition across the exons.

PMID- 16788951
TI  - Localization of CYP4B1 in the rat nasal cavity and analysis of CYPs as secreted
      proteins.
AB  - CYP4B1 is highly expressed in rat nasal respiratory mucosa, and to a lesser
      extent in olfactory mucosa. Examination of high-power photomicrographs suggests
      that CYP4B1 may be a secreted protein, based on the fact that immunoreactivity
      appears to be present in the lumens of ducts of Bowman's glands (rather than
      intracellular localization, as we observed with an antibody recognizing CYP2F4)
      and in secretory granules in respiratory mucosa. Furthermore, anti-CYP4B1
      immunoreactivity is present on the surface of both respiratory and olfactory
      mucosa. We used SignalP 3.0 analysis to ascertain the likelihood that rat CYP4B1
      is a secreted protein. While this analysis does not suggest that rat CYP4B1 is a
      secreted protein, several other cytochrome P450 enzymes were predicted to be
      secreted proteins. The observation that multiple human cytochrome P450s appear to
      be secreted proteins helps to explain the appearance of anti-cytochrome P450
      antigens in cases of human autoimmune liver diseases.

PMID- 16788953
TI  - Interaction of diuron and related substituted phenylureas with the Ah receptor
      pathway.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      that mediates many of the biological and toxicological actions of structurally
      diverse chemicals, including the ubiquitous environmental contaminant 2,3,7,8
      tetrachlorodibenzo-p-dioxin. Here, we have examined the ability of diuron, a
      widely used herbicide, and several structurally related substituted phenylureas
      to bind to and activate/inhibit the AhR and AhR signal transduction. Diuron
      induced CYP1A1 mRNA levels in mouse hepatoma (Hepa1c1c7) cells and AhR-dependent
      luciferase reporter gene expression in stably transfected mouse, rat, guinea pig,
      and human cell lines. In addition, ligand binding and gel retardation analysis
      demonstrated the ability of diuron to competitively bind to and stimulate AhR
      transformation and DNA binding in vitro and in intact cells. Several structurally
      related substituted phenylureas competitively bound to the guinea pig hepatic
      cytosolic AhR, inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced AhR
      dependent luciferase reporter gene expression in a species-specific manner and
      stimulated AhR transformation and DNA binding, consistent with their role as
      partial AhR agonists. These results demonstrate not only that diuron and related
      substituted phenylureas are AhR ligands but also that exposure to these chemicals
      could induce/inhibit AhR-dependent biological effects.

PMID- 16788954
TI  - Modulation of the expression of superoxide dismutase gene in lung injury by 2
      chloroethyl ethyl sulfide, a mustard analog.
AB  - Mustard gas exposure causes inflammatory lung diseases. Many inflammatory lung
      diseases are associated with oxidative stress. Reactive oxygen species (ROS) are
      involved in the maintenance of physiological functions. In tissues, it is
      therefore essential to maintain a steady-state level of antioxidant activity to
      allow both for the physiological functions of ROS to proceed and at the same time
      preventing tissue damage. We have recently reported that mustard gas exposure
      decreases the overall activity of superoxide dismutase (SOD). In the present
      study, we investigated the effects of mustard gas on each of the three isozymes:
      SOD-1 (Cu/Zn), SOD-2 (Mn), and SOD-3 (extracellular). Adult guinea pigs were
      intratracheally injected single doses of 2-chloroethyl ethyl sulfide (CEES) (2
      mg/kg body weight) in ethanol. Control animals were injected with vehicle in the
      same way. The animals were sacrificed after 7 days, and lungs were removed after
      perfusion with physiological saline. Lung injury was established by measuring the
      leakage of iodinated-BSA into lung tissue. Mustard gas exposure caused a
      significant increase in the activity of SOD-1 (35%). However, the SOD-3 activity
      which is the predominant type in lung was significantly decreased (62%), whereas
      no change was observed in SOD-2 activity. Thus the decrease in the total activity
      of SOD was primarily due to the SOD-3 isozyme. Northern blot analysis indicated
      3.5-fold increased expression of SOD-1 in mustard gas exposed lung, but no
      significant change in the expression of SOD-2 and SOD-3 was observed. Mustard gas
      exposure did not cause mutation in the coding region of SOD-1 gene while causing
      modulation in expression levels. The protein levels of SOD-1, SOD-2, and SOD-3
      were not altered significantly in the mustard gas exposed lung. Our results
      indicate that the overall decrease in the activity of SOD by mustard gas exposure
      is probably mediated by direct inactivation of the SOD-3 gene or the enzyme
      itself. This decrease in the activity of SOD-3 may be due to the cleavage of
      active form of the protein to an inactive form. The existence of active and
      inactive forms of SOD-3 as a result of shifts in Cys-Cys disulfide bonding has
      been described in human, recently. Studies are underway in our laboratory to
      investigate whether mustard gas induced inactivation of SOD-3 in lung is
      similarly mediated by a change in Cys-Cys disulfide bonding.

PMID- 16788955
TI  - Molecular cloning and characterization of alpha-class glutathione S-transferase
      gene from the liver of silver carp, bighead carp, and other major Chinese
      freshwater fishes.
AB  - Two full-length cDNAs encoding glutathione S-transferase (GST) were cloned and
      sequenced from the hepatopancreas of planktivorous silver carp
      (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis). The silver
      carp and bighead carp GST cDNA were 920 and 978 bp in length, respectively, and
      both contained an open reading frame that encoding 223 amino acids. Partial GST
      cDNA sequences were also obtained from the liver of grass carp (Ctenopharyngodon
      idellus), crucian carp (Carassius auratu), mud carp (Cirrhinus molitorella), and
      tilapia (Oreochromis nilotica). All these GSTs could be classified as alpha-class
      GSTs on the basis of their amino acid sequence identity with other species. The
      three-dimensional structure of the silver carp GST was predicted using a computer
      program, and was found to fit the classical two-domain GST structure. Using the
      genome walker method, a 875-bp 5'-flanking region of the silver carp GST gene was
      obtained, and several lipopolysaccharide (LPS) response elements were identified
      in the promoter region of the phytoplanktivorous fish GST gene, indicating that
      the GST gene expression of this fish might be regulated by LPS, released from the
      toxic blue-green algae producing microcystins. To compare the constitutive
      expression level of the liver GST gene among the six freshwater fishes with
      completely different tolerance to microcystins, beta-actin was used as control
      and the ratio GST/beta-actin mRNA (%) was determined as 130.7 +/- 6.6 (grass
      carp), 103.1 +/- 8.9 (bighead carp), 92.6 +/- 15.0 (crucian carp), 72.3 +/- 7.8
      (mud carp), 58.8 +/- 11.5 (silver carp), and 33.6 +/- 13.7 (tilapia). The
      constitutive expression level of the liver GST gene clearly shows that all the
      six freshwater fishes had a negative relationship with their tolerance to
      microcystins: high-resistant fishes (phytoplanktivorous silver carp and tilapia)
      had the lowest tolerance to microcystins and the high-sensitive fish (herbivorous
      grass carp) had the highest tolerance to microcystins. Taken together with the
      reciprocal relationship of constitutive and inducible liver GST expression level
      in some of the tested fish species to microcystin exposure, a molecular mechanism
      for different microcystin detoxification abilities of the warm freshwater fishes
      was discussed.

PMID- 16788956
TI  - Biochemical modifications induced in human blood by oxygenation-ozonation.
AB  - Some biochemical effects determined on human blood after addition of a gas
      mixture composed of oxygen (approximately 96%) and ozone (approximately 4%) have
      been evaluated. Ozone was used in a mild concentration ranging between 0.21 and
      1.68 mM. Within few minutes after rapid mixing of the equal gas-liquid volumes,
      the ozone was consumed because by instantaneously reacting with biomolecules,
      generating reactive oxygen species (particularly hydrogen peroxide) having very
      short lifetime and lipid oxidation products. The following results are oxygen
      ozone dose dependent: (1) The pO(2) values have risen from about 40 up to 400
      mmHg. (2) By testing the highest ozone concentration, the total antioxidant
      capacity of blood decreased within 1 min from 1.35 to 0.91 mM but regained its
      normal values within 20 min owing to the rapid reduction of oxidized antioxidants
      operated by erythrocytes. (3) Similarly, intraerythrocytic reduced glutathione
      after ozonation decreased from the initial value of 5.71 to 4.56 micromol/g Hb.
      (4) Both hemolysis and methemoglobin showed a negligible increase.

PMID- 16788957
TI  - Characterization of focal liver lesions using contrast-enhanced sonography with a
      low mechanical index mode and a sulfur hexafluoride-filled microbubble contrast
      agent.
AB  - PURPOSE: To characterize focal liver lesions (FLLs) using real-time contrast
      enhancedsonography (CEUS) with a low mechanical index mode and a sulfur
      hexafluoride-filled microbubble contrast agent. METHODS: CEUS was performed in
      190 patients with FLLs, including hepatocellular carcinoma (HCC) (n = 107), liver
      metastasis (n = 21), intrahepatic cholangiocarcinoma (ICC) (n = 7), liver
      hemangioma (n = 37), focal nodular hyperplasia (FNH) (n = 11), regenerative
      nodule (n = 6) and liver lipoma (n = 1). The cadence contrast pulse sequencing
      technique and the contrast agent SonoVue(R) were used for CEUS examination. The
      enhancement patterns during the arterial, portal, and late phases were evaluated.
      RESULTS: HCC showed hyperenhancement in 100 (93.5%) of 107 nodules during the
      arterial phase and hypoenhancement in 102 (95.3%) during the late phase. Liver
      metastases showed homogeneous enhancement in 8 of 21 (38.1%) nodules and a
      peripheral regular rim-like enhancement in 11 of 21 (52.4%) nodules during the
      arterial phase and marked hypoenhancement in 16 of 21 (76.2%) nodules during the
      late phase. ICC exhibited irregular rim-like enhancement in 4 of 7 (57.1%)
      nodules during the arterial phase and hypo-enhancement in 7 of 7 (100%) nodules
      during the late phase. Hemangioma showed peripheral nodular hyperenhancement, and
      progressive centripetal enhancement was seen in 35 of 37 (94.6%) lesions during
      the arterial phase. All 11 cases of FNH exhibited homogeneous hyperenhancement
      during the arterial phase and hyperenhancement (n = 1) or isoenhancement (n = 9)
      during the late phase. The sensitivity, specificity, and positive predictive
      value, respectively, were 88.8%, 89.2%, and 91.3% for HCC; 81%, 100%, and 100%
      for liver metastasis; 57.1%, 100%, and 100% for ICC; 94.6%, 100%, and 100% for
      liver hemangioma; and 90.9%, 97.8%, and 71.4% for FNH. CONCLUSIONS: Low
      mechanical index CEUS permits real-time, complete assessment of vascularity in
      FLLs, which in turn facilitates their characterization.

PMID- 16788958
TI  - Sonographic and mammographic findings of breast liquid silicone injection.
AB  - PURPOSE: To describe the sonographic and mammographic features of patients whose
      breasts have been injected with silicone. METHODS: Between July 1997 and August
      1999, 14 patients with a history of breast injection of liquid silicone underwent
      physical, mammographic, and sonographic examination. Mammographic findings were
      classified as macronodular, micronodular, or mixed striated patterns. Sonographic
      appearances were classified as macronodular, micronodular, mixed, or snowstorm
      patterns. RESULTS: Eighty-six percent of the patients had abnormal physical
      examination. Well-defined nodules were palpable in 4 patients, 6 patients had
      diffusely heterogeneous breasts on palpation, and 2 patients had a combination of
      heterogeneous texture with dominant nodules. Sonographic examination revealed the
      presence of marked echogenicity (i.e., snowstorm pattern) in all 14 patients; in
      11 patients it was associated with macronodules and/or micronodules, whereas in 3
      patients only snowstorm appearance was noted. Mammographic patterns were
      macronodular in 7 patients and mixed macronodular and micronodular in 6 patients.
      CONCLUSIONS: Both mammography and sonography can help identify free silicone
      injected directly into the breast.

PMID- 16788959
TI  - Sonographic appearance of the uterine cavity following administration of
      mifepristone and misoprostol for termination of pregnancy.
AB  - PURPOSE: To describe the sonographic appearance of the uterine cavity in women
      after administration of mifepristone and misoprostol for termination of
      pregnancy. METHODS: Thirty-six women treated with mifepristone 600 mg followed by
      misoprostol 400 mug 2 days later for termination of pregnancy were the subjects
      of the study. Gestational age as calculated from the last menstrual period was <
      or =49 days. Pretreatment sonographic parameters, including gestational sac size
      and crown-rump length, were measured. The sonographic appearance of the uterine
      cavity was recorded and documented 6 hours (T-1) and 14 days (T-2) after
      administration of misoprostol. RESULTS: The mean menstrual age of the patients
      was 42 days (range 31-49 days). The mean gestational age according to crown-rump
      length was 43 days (range 40-48 days). Sonographic examination performed atT-1
      revealed 23 patients (62.9%) with a well-defined echogenic mass located in the
      uterine cavity, 2 patients (5.5%) with an intrauterine sac containing a nonviable
      embryo, and 11 patients (30.5%) with an endometrium thickness of 7-14 mm with no
      evidence of intrauterine contents. Doppler flow signals were detected in 15 of
      the 23 patients (65.2%) with an echogenic intrauterine mass. Sonographic
      examination performed at T-2 revealed 19 patients (52.8%) with a persistent
      echogenic intrauterine mass; Doppler flow could be detected in 15 of these
      patients (78.9%). Dilatation and curettage was required in 2 patients (5.6%) due
      to failure of treatment; all others regained normal menses. CONCLUSIONS: An
      intrauterine echogenic mass with well-defined borders, with or without Doppler
      flow signals, can be detected 2 weeks after administration of mifepristone and
      misoprostol for termination of pregnancy. Because most of the women in our study
      regained normal menses without further surgical intervention, this finding could
      indicate remnants of trophoblastic tissue evacuated spontaneously from the
      uterine cavity. Therefore, dilatation and curettage should be avoided in these
      cases, unless clinical symptoms or signs necessitate surgical intervention.

PMID- 16788960
TI  - Role of hyperlipidemia in atherosclerotic plaque formation in the internal
      carotid artery.
AB  - PURPOSE: The role of hyperlipidemia in atherosclerotic changes of the carotid
      artery is controversial. The aims of this retrospective study were to assess (1)
      the relationship between total serum cholesterol and triglyceride and the grade
      of internal carotid artery stenosis and (2) whether total serum cholesterol and
      triglyceride levels are independent risk factors for internal carotid artery
      atherosclerosis. METHODS: The files of 1,934 acute ischemic stroke patients were
      investigated retrospectively. The atherosclerotic involvement of the internal
      carotid artery was assessed via duplex sonography as percent of stenosis and was
      graded as follows: group 1, no plaque; group 2, <30% stenosis; group 3, 30-99%
      stenosis; and group 4, occlusion. RESULTS: The mean age of the patients was 66.9
      +/- 12.8 years. Patients without any plaque had significantly lower cholesterol
      levels compared with those with any degree of internal carotid artery stenosis.
      Univariate analysis revealed that age (p < 0.001), sex (p < 0.001), hypertension
      (p < 0.05), cholesterol (p < 0.01), triglycerides(p < 0.05), and smoking (p <
      0.001) were significant contributors to atherosclerosis. In the ordinal logistic
      regression model, age (p < 0.001), sex (p < 0.001), smoking(p < 0.001), and
      cholesterol (p < 0.05) remained independent predictors of internal carotid artery
      atherosclerosis. CONCLUSIONS: Total serum cholesterol level seems to be an
      independent risk factor of atherosclerosis in the carotid artery.

PMID- 16788961
TI  - Current approaches and controversial issues in the diagnosis of deep vein
      thrombosis via duplex Doppler ultrasound.
AB  - Duplex and color Doppler sonography (DUS) is currently the technique of choice
      for the diagnosis of deep venous thrombosis (DVT) in symptomatic patients,
      because it has proven safe and cost-effective, with a very high sensitivity and
      specificity (96% and 98%, respectively) for the diagnosis of proximal DVT.
      Several issues regarding its method and clinical indications remain
      controversial, however. Although isolated calf vein thrombosis does not seem to
      have a significant adverse outcome in the short term, scanning the calf only in
      patients with localized symptoms or signs is cost-effective. Bilateral
      examination is indicated in high-risk patients or when screening asymptomatic
      patients. When negative, a complete DUS examination of the proximal and distal
      veins, at least down to the level of the popliteal trifurcation, allows
      withholding anticoagulant therapy without the risk of major complications. This
      examination may be repeated if signs or symptoms worsen. Some populations of
      asymptomatic patients at high risk of DVT may benefit from DUS screening.
      Bilateral DUS examination of lower limb veins should be performed as the initial
      examination in the workflow of pulmonary embolism only in patients with risk
      factors for DVT. Recurrent thrombosis is a challenging diagnosis for all imaging
      modalities. A diagnostic strategy combining clinical probability score and D
      dimer test may refine the selection of patients. The pitfalls and limitations of
      venous DUS are related to vein anatomy, flow changes, technical issues, and
      operator expertise.

PMID- 16788962
TI  - Lymphoepithelial cyst of the thyroid mimicking malignancy on sonography.
AB  - A 52-year-old man presented with a palpable left neck mass that had been present
      for several months. A sonogram showed a 2-cm hypoechoic mass with internal coarse
      macrocalcifications in the left lobe of the thyroid gland. CT revealed a well
      demarcated hypodense mass within the left thyroid lobe. A left thyroidectomy was
      performed at the patient's request because of the possibility of malignancy based
      on sonographic findings. Pathologically, the mass was composed of
      pseudostratified ciliated columnar epithelial cells simulating respiratory
      epithelium surrounded by florid lymphoid hyperplasia with germinal centers,
      consistent with an intrathyroidal lymphoepithelial cyst.

PMID- 16788963
TI  - Prenatal diagnosis of holoprosencephaly with ethmocephaly via 3-dimensional
      sonography.
AB  - We present the prenatal 3-dimensional (3D) sonographic findings in a case of
      holoprosencephaly with ethmocephaly at 32 weeks' gestation. The sonographic
      diagnosis was based on the intracranial findings of a single ventricle and bulb
      shaped appearance of the thalami and facial abnormalities, including hypotelorism
      with proboscis. Chromosome study of the fetus revealed a normal female karyotype
      (46,XX). Postmortem examination confirmed the 3D sonographic findings. This case
      demonstrates that the use of 3D sonography improves the imaging and the
      understanding of the condition of the intracranial abnormalities and the facial
      anomalies.

PMID- 16788964
TI  - Transperineal sonography of a large vulvar hematoma following blunt perineal
      trauma.
AB  - Vulvar hematomas may result from puerperal or nonpuerperal-related trauma. These
      perineal injuries, especially the puerperal type, may be life-threatening and
      require surgical exploration, evacuation, and hemostasis. In the absence of acute
      hematoma expansion, expectant management may suffice. Experience with
      transperineal sonography in the assessment of female perineal trauma has been
      limited to a single case report pertaining to a puerperal vulvar hematoma. We
      present an unusual case in which the transperineal sonographic appearance of a
      large vulvar hematoma following a straddle injury to the perineum assisted in the
      expectant management of this condition.

PMID- 16788965
TI  - A case of lipomatous hypertrophy of the interatrial septum detected via
      transthoracic 2-dimensional echocardiography.
AB  - A 71-year-old woman underwent echocardiography for the evaluation of hypertensive
      heart disease. A 2-dimensional echocardiogram revealed an abnormal mass that
      protruded into the left atrium from the atrial septal side of the left atrial
      wall. Microscopic examination of the surgical specimen disclosed a mixture of
      normal-appearing fat, vesicular fat, and hypertrophied myocytes, and degenerated
      cardiac tissue with foci of necrotic fat tissue, consistent with lipomatous
      hypertrophy. Although lipomatous hypertrophy of the interatrial septum is rare,
      this little-known entity should be included in the differential consideration of
      the left atrial mass detected via echocardiographic examination, particularly in
      both obese and elderly patients.

PMID- 16788966
TI  - Iatrogenic carotid-jugular arteriovenous fistula: color Doppler sonographic
      findings and treatment with covered stent.
AB  - We describe the case of a 68-year-old woman who presented with an arteriovenous
      fistula (AVF) between the common carotid artery and internal jugular vein
      following several failed attempts of right jugular catheter insertion.
      Sonographic examination revealed an AVF between both vessels with a high-velocity
      turbulent flow inside and an arterialized waveform in the jugular vein.
      Angiography confirmed the sonographic findings, and endovascular treatment was
      performed with a covered stent.

PMID- 16788967
TI  - Branch to colony trajectory in a modular organism: pattern formation in the Indo
      Pacific coral Stylophora pistillata.
AB  - The architecture of the colony in a branching coral is an iterative process in
      which new layers of calcium carbonate compile atop existing structures that
      remain unchanged. Colony growth and development, known as astogeny, is believed
      to be a continuous process, characterized by replication of lower rank unites,
      polyps, and branches. This study seeks to explore the genetic blueprint of branch
      to-colony developmental trajectory in the branching coral Stylophora pistillata,
      within an astogeny period of 1 year. One hundred small branches (initially 2-4 cm
      long) were sampled from 10 colonies. A year later, 63 remaining colonies were
      analyzed for their architectural rules by using 15 morphometric parameters.
      Multivariate statistical tests were preformed. Cluster and two-dimensional
      nonmetric Multi-Dimensional Scaling analyses revealed that the 10 genotypes could
      be divided into two major morphometric groups and two intermediate groups,
      whereas SIMPER analyses (a similarity percentage test) on within-genet
      similarities showed high similarity between the ramets developed from each of the
      10 genotypes. Although, at first, it seemed that different colonies exhibited
      variable and different architectural designs (each characterized by specific
      morphometric parameters), a comprehensive analysis revealed that all 10 coral
      genotypes exhibited a single common developmental plan that was characterized by
      a continuum of architectural design with several distinct stages. Each stage is
      marked by its own characteristic morphometric parameters. Changing of
      developmental rules during the trajectory from branch to coral colony may help
      the colony to cope better with environmental constraints.

PMID- 16788968
TI  - Effects of bone protein extract on human mesenchymal stem cells proliferation and
      differentiation.
AB  - Since its osteoinductive capacity has been established, demineralized bone matrix
      is considered a suitable alternative to bone autograft in the healing of osseous
      defects. The mechanisms of bone formation induction are still not fully
      understood. In this study we assessed the effects of a dispersion of bovine bone
      extract COLLOSS (BPE) with regard to proliferation and differentiation of a human
      mesenchymal stem cell line overexpressing human telomerase reverse transcriptase
      (hMSC-TERT). Proliferation rate was determined by (3)H-thymidine incorporation.
      The differentiation of hMSC-TERT cells to osteoblastic cells was assessed by
      means of measuring alkaline phosphatase activity and collagen synthesis in vitro.
      Both undifferentiated and osteoblast-differentiated hMSC-TERT cells were
      investigated for response to BPE. The metabolic responses to BPE were compared to
      unstimulated cells and cells stimulated with bovine collagen (COL).
      Undifferentiated hMSC-TERT cells responded to BPE with increased proliferation
      and decreased alkaline phosphatase activity. Osteoblastic differentiated hMSC
      TERT cells had a diminished proliferative response and an increased alkaline
      phosphatase activity and collagen synthesis. Our study demonstrated significant
      metabolic effects of BPE on hMSC-TERT cells, which were highly dependant on the
      differentiated state of the cells.

PMID- 16788969
TI  - Glass-glass ceramic thermoseeds for hyperthermic treatment of bone tumors.
AB  - Implantable thermoseeds are synthesised from mixtures of a melt-derived glass
      with composition SiO(2) (40)-CaO(40)-Fe(2)O(3)(20) (mol%) and a sol-gel glass
      with composition SiO(2)(58)-P(2)O(5)(6)-CaO(36) (mol%). Structural, textural and
      magnetic properties of the samples are evaluated. In vitro bioactivity is
      assessed in order to determine the potential capability to bond to living bone.
      In spite of the low textural properties of the material, a bioactive behavior is
      observed as a result of the sol-gel glass content. Although the crystallization
      of the glass ceramic provides the magnetic phase, the presence of sol-gel glass
      modifies the magnetic properties, improving the heating power. For the first
      time, hyperthermia heating experiments as well as preliminary biocompatibility
      assays have been carried out for this kind of material. The ability to reach
      hyperthermic temperature range together with the bioactive behavior makes this
      biomaterial a very promising candidate for bone cancer treatment.

PMID- 16788970
TI  - Synthesis and characterization of uniform radiopaque polystyrene microspheres for
      X-ray imaging by a single-step swelling process.
AB  - Uniform radiopaque polystyrene microspheres of approximately 2.3 +/- 0.2 microm
      were prepared by a single-step swelling of 2.3 +/- 0.2 microm polystyrene
      template microspheres, dispersed in an aqueous solution with methylene chloride
      emulsion droplets containing 2,3,5-triiodobenzoylethyl ester. After completing
      the swelling process, the methylene chloride was evaporated in order to lock the
      2,3,5-triiodobenzoylethyl ester in the polystyrene microspheres. The influence of
      the weight ratio [2,3,5-triiodobenzoylethyl ester]/[polystyrene] on the % of
      entrapped 2,3,5-triiodobenzoylethyl ester was elucidated. Characterization of the
      radiopaque polystyrene microspheres was accomplished by light microscope, FTIR,
      TGA, SEM, XPS, and elemental analysis. The radiopacity of the microspheres was
      demonstrated by an imaging technique based on X-ray absorption usually used in
      hospitals. This novel method of encapsulation of 2,3,5-triiodobenzoylethyl ester
      within polystyrene microspheres by a single-step swelling process may be used as
      a model for encapsulation of various hydrophobic radiopaque drugs within uniform
      polystyrene template particles of various diameters for different X-ray imaging
      needs, e.g., blood pool, body organs, embolization, dental composition, implants,
      protheses, and nanocomposites.

PMID- 16788971
TI  - Nanostructured niobium oxide coatings influence osteoblast adhesion.
AB  - The interaction of osteoblasts was correlated to the roughness of nanosized
      surface structures of Nb(2)O(5) coatings on polished CP titanium grade 2.
      Nb(2)O(5) sol-gel coatings were selected as a model surface to study the
      interaction of osteoblasts with nanosized surface structures. The surface
      roughness was quantified by determination of the average surface finish (Ra
      number) by means of atomic force microscopy. Surface topographies with Ra = 7,
      15, and 40 nm were adjusted by means of the annealing process parameters (time
      and temperature) within a sol-gel coating procedure. The observed osteoblast
      migration was fastest on smooth surfaces with Ra = 7 nm. The adhesion strength,
      spreading area, and collagen-I synthesis showed the best results on an
      intermediate roughness of Ra = 15 nm. The surface roughness of Ra = 40 nm was
      rather peaked and reduced the speed of cell reactions belonging to the adhesion
      process.

PMID- 16788972
TI  - Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and
      entrapment.
AB  - Micropatterning of hydrogels is potentially useful for a variety of applications,
      including tissue engineering, fundamental biological studies, diagnostics, and
      high-throughput screening. Although synthetic polymers have been developed for
      these applications, natural polymers such as polysaccharides may have advantages
      for biological samples and cell-based devices because they are natural components
      of the in vivo microenvironment. In this study, we synthesized and used
      hyaluronic acid (HA) modified with photoreactive methacrylates to fabricate
      microstructures as functional components of microfabricated devices. To
      demonstrate the universality of this approach, two types of microstructures were
      formed. In the first approach, HA microstructures were fabricated and used as
      docking templates to enable the subsequent formation of cell microarrays within
      low shear stress regions of the patterns. Cells within these microwells remained
      viable, could generate spheroids, and could be retrieved using mechanical
      disruption. In the second approach, cells were encapsulated directly within the
      HA hydrogels. Arrays of viable embryonic stem (ES) cells or fibroblasts were
      encapsulated within HA hydrogels and could later be recovered using enzymatic
      digestion of the microstructures. These results demonstrate that it is possible
      to incorporate photocrosslinkable HA, a natural, versatile, degradable, and
      biocompatible biopolymer, into micro-electromechanical systems.

PMID- 16788973
TI  - Nickel and vanadium metal ions induce apoptosis of T-lymphocyte Jurkat cells.
AB  - Metal alloys are used as prosthetic components in the orthopaedic and dental
      field. However, there is growing concern over the reported leaching of metal ions
      from implants. Ions released from metals have been thought to be associated with
      local immune dysfunction, inflammation, and tissue cell death. The objective of
      our study was to investigate whether nickel(II) and vanadium(V), present at a
      smaller percentage in most alloys, are cytotoxic to T-lymphocyte cell models.
      Jurkat T cells possess characteristics similar to human T-lymphocytes and
      proliferate at a faster rate. Jurkat T cells were incubated with control media
      alone or with concentrations of 1, 10, and 100 microg/mL of Ni(II) or V(V) for 24
      h. Both types of metal ions reduced cell viability and proliferation in a dose
      dependent manner. Ni(II) at 10 microg/mL and V(V) at 100 microg/mL activated
      Caspase-3 expression. Hoechst 33258 staining and transmission electron microscopy
      revealed chromatin condensation, as well as nuclear blebbing and fragmentation.
      Induction of DNA fragmentation by Ni(II) at 100 microg/mL was also indicated by
      agarose electrophoresis. Our observations indicate that Ni and V ions kill T
      cells via apoptotic and nonapoptotic pathways.

PMID- 16788974
TI  - Closing capacity of cranial bone defects using porous calcium phosphate cement
      implants in a rabbit animal model.
AB  - Calcium phosphate (Ca-P) cement is a well established material for bone repair.
      The bone biological properties of Ca-P cement can even be further improved by
      creating porosity in the material. The current study aimed on the evaluation of
      the osteoconductive behavior of porous Ca-P cement. Therefore, circular defects
      (6, 9, and 15 mm in diameter) were created in the cranium of 3 months old rabbits
      and filled with porous Ca-P cement implants. The total porosity of implants was
      calculated to be 71, 74 and 74% respectively and the average pore diameter was
      150 microm. In addition, empty control defects were prepared. After 12 weeks
      implantation time the animals were sacrificed and radiographic, histological, and
      histomorphometrical evaluation was performed. The Critical Size Defect (CSD) of
      this species at this location for an implantation time of 12 weeks was confirmed
      to be 15 mm. Bone was observed to be present over and through almost all porous
      Ca-P cement implants. Only, in one out of eight animals with a 15 mm implant
      complete bone bridging of the defect did not occur. The size of the defect was
      found not to affect the total percentage of bone formation in the cement; (17 +/-
      7)%, (18 +/- 6)% and (17 +/- 3)% for respectively 6, 9, and 15 mm diameter
      implants. We concluded that porous Ca-P cement is an excellent osteoconductive
      material in non weight bearing situations and complete bridging of a critical
      sized skull defect occurs in this rabbit model after 12 weeks of implantation.

PMID- 16788975
TI  - Survival and differentiation of embryonic neural explants on different
      biomaterials.
AB  - Biomaterials prepared from polyacrylamide, ethyl acrylate (EA), and hydroxyethyl
      acrylate (HEA) in various blend ratios, methyl acrylate and chitosan, were tested
      in vitro as culture substrates and compared for their ability to be colonized by
      the cells migrating from embryonic brain explants. Neural explants were isolated
      from proliferative areas of the medial ganglionic eminence and the cortical
      ventricular zone of embryonic rat brains and cultured in vitro on the different
      biomaterials. Chitosan, poly(methyl acrylate), and the 50% wt copolymer of EA and
      HEA were the most suitable substrates to promote cell attachment and
      differentiation of the neural cells among those tested. Immunofluorescence
      microscopy analysis showed that progenitor cells had undergone differentiation
      and that the resulting glial and neuronal cells expressed their intrinsic
      morphological characteristics in culture.

PMID- 16788976
TI  - The biocompatibility and osteoconductivity of a cement containing beta-TCP for
      use in vertebroplasty.
AB  - A new composite bone cement designated "G2B1" was developed for percutaneous
      transpedicular vertebroplasty. G2B1 contains beta tricalcium phosphate particles
      and methylmethacrylate-methylacrylate copolymer as the powder components, and
      methylmethacrylate, urethane dimethacrylate, and tetrahydrofurfuryl methacrylate
      as the liquid components. Biocompatibility and osteoconductivity were evaluated
      using scanning electron microscopy, contact microradiography, and Giemsa surface
      staining 4, 8, 12, 26, and 52 weeks after implantation into rat tibiae. To
      evaluate osteoconductivity, affinity indices (%) were calculated. Scanning
      electron microscopy and contact microradiography revealed that bone contact with
      G2B1 was attained within 4 weeks (affinity index: 50.2 +/- 11.8 at 4 weeks) and
      at most of the margin within 26 weeks (affinity index: 87.4 +/- 7.2 at 26 weeks).
      Specifically, G2B1 contacted bone via a wide calcium-phosphate-rich layer, and
      its degradation started within 8 weeks, mainly in the marginal area. Giemsa
      surface staining showed that there was almost no inflammatory reaction around the
      G2B1. These results indicate that G2B1 is a biocompatible and osteoconductive
      bone cement.

PMID- 16788977
TI  - Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and
      development.
AB  - Conventional anticancer therapy using cytotoxic drugs lacks selectivity and is
      prone to toxicity and drug resistance. Anticancer therapies targeting aberrant
      growth factor receptor signaling are gaining interest. The erbB receptor family
      belongs to the type I, the receptor tyrosine kinases class, and comprises EGFR,
      HER-2, HER-3, and HER-4. It has been targeted for solid tumor therapy, including
      breast, ovarian, colon, head-and-neck, and non-small-cell lung cancers. This
      review summarizes structural aspects of this class of growth factor receptors,
      their oncogenic expression, and various pharmacological interventions including
      biological products and small molecules that inhibit these enzymes. We have also
      discussed various mutations that occur in EGFR and their consequences on
      anticancer therapy.

PMID- 16788978
TI  - Visualizing soft tissue in the mammalian cochlea with coherent hard X-rays.
AB  - This paper concerns an important aspect of current developments in medical and
      biological imaging: the possibility for imaging soft tissue at relatively high
      resolution in the micrometer range or better, without tedious and/or entirely
      destructive sample preparation. Structures with low absorption contrast have been
      visualized using in-line phase contrast imaging. The experiments have been
      performed at the Advanced Photon Source, a third generation source of synchrotron
      radiation. The source provides highly coherent X-ray radiation with high photon
      flux (>10(14) photons/s) at high photon energies (5-70 keV). Thick gerbil
      cochlear slices have been imaged and were compared with those obtained by light
      microscopy. Furthermore, intact gerbil cochleae have been imaged to identify the
      soft tissue structures involved in the hearing process. The present experimental
      approach was essential for visualizing the inner ear structures involved in the
      hearing process in an intact cochlea.

PMID- 16788979
TI  - Vinyl sulfones: synthetic preparations and medicinal chemistry applications.
AB  - Vinyl sulfones have long been known for their synthetic utility in organic
      chemistry, easily participating in 1,4-addition reactions and cycloaddition
      reactions. This functional group has also recently been shown to potently inhibit
      a variety of enzymatic processes providing unique properties for drug design and
      medicinal chemistry. This review includes traditional methods used for the
      synthesis of vinyl sulfones, but focuses mainly on newer reactions applied to
      vinyl sulfones, including olefin metathesis, conjugate reduction, asymmetric
      dihydroxylation (AD), and the use of vinyl sulfones to arrive at highly
      functionalized targets, all illustrating the rich and versatile chemistry this
      group can efficiently perform. In addition, geminal disulfones are discussed with
      respect to their formation, reactions, and medicinal applications of this
      underutilized functional group.

PMID- 16788980
TI  - Indole, a core nucleus for potent inhibitors of tubulin polymerization.
AB  - Microtubules are the basic components of cell structure, which take part in a
      wide number of pivotal cellular functions. Drugs that are able to modulate the
      microtubule assembly either by inhibition of tubulin polymerization or by
      blocking microtubule disassembly are of great interest in anti-cancer therapy.
      Several tubulin polymerization inhibitors characterized by the presence of an
      indole nucleus have been obtained from natural sources or have been prepared by
      semi-synthesis. In the last decade an ever increasing number of synthetic indoles
      have been reported. We have reviewed anti-tubulin agents obtained by synthesis
      having an indole as core nucleus. The synthesis, the biological activity, and the
      structure - activity relationship aspects of 3-formyl-2-phenylindoles,
      heterocombretastatins, diarylindoles, 2-aroylindoles, D-24851, 2-aryl-3
      aroylindoles, 3-aroyl- and 1-aroylindoles, and arylthioindoles are discussed.

PMID- 16788981
TI  - Endoscopic laser speckle imaging of tissue blood flow: applications in the human
      knee.
AB  - This work represents the first clinical data acquired with the endoscopic laser
      speckle imaging (eLSPI) system, a new diagnostic tool developed for real-time
      imaging of tissue blood flow during endoscopic surgical procedures. eLSPI was
      used to image tissue perfusion in the medial compartment of the knee of five
      patients requiring arthroscopic knee surgery. The effectiveness of eLSPI as a
      diagnostic tool was tested by measuring changes in tissue perfusion resultant
      from tourniquet application, and intra-articular epinephrine. eLSPI produced real
      time perfusion video images of tissue blood flow in the knee joint. Tourniquet
      applications produced consistent decreases in mean perfusion index measurements
      (29.3% +/- 5.1% in meniscus; 39.5% +/- 8.2% in synovium with an intra patient
      variability of 6%-9%). A dose-dependent vasoconstrictive response to the
      administration of intra-articular epinephrine was measured, with maximum dose
      producing a mean decrease in perfusion of 31.0%-9.3% in meniscus and 41.2%-10.9%
      in synovium. eLSPI consistently detects decreases in articular tissue blood flow
      resultant from tourniquet inflation or from the administration of increasing
      concentrations of epinephrine. These are the first in vivo results indicating
      physiologic changes in articular tissue as a function of two commonly applied
      practices in endoscopic joint surgery.

PMID- 16788982
TI  - Mesenchymal transformation in epithelial ovarian tumor cells expressing epidermal
      growth factor receptor variant III.
AB  - Overexpression of the epidermal growth factor (EGF) receptor occurs frequently in
      ovarian cancer and is associated with poor patient prognosis. A constitutively
      active mutant EGF receptor termed variant III (EGFRvIII) has been detected at a
      high frequency in many human tumors, including those of the ovary. To identify
      the consequences of EGFRvIII expression in ovarian tumor cells, we introduced
      EGFRvIII into the epithelial ovarian cancer cell line (OVCA 433). The EGFRvIII
      transfected cells displayed a dissociated, motile phenotype and fibroblastic
      morphology. The EGFRvIII-dependent phenotype was comparable to that observed in
      EGF-stimulated parental OVCA 433 cultures and required the catalytic activity of
      the mutant receptor. Disruption of adherens and desmosomal junctions in EGFRvIII
      expressing cells was evident by immunofluorescent detection of specific
      junctional components. In addition, Western blot analysis confirmed decreased
      levels of cellular plakoglobin and beta-catenin in EGFRvIII-expressing cells, and
      E-cadherin protein and mRNA were nearly absent. The loss of E-cadherin was
      accompanied by decreased expression of additional ovarian epithelial markers,
      including keratins 7, 8, and 18 and mucins 1 and 4. In contrast, the mesenchymal
      markers N-cadherin and vimentin were elevated in EGFRvIII expressing cells.
      Overall, the switch in cadherins from E-cadherin to N-cadherin, coupled with gain
      of vimentin expression and loss of the epithelial keratins and mucins typically
      expressed in well-differentiated epithelial ovarian carcinomas, are consistent
      with transition to a mesenchymal phenotype as an outcome of EGFRvIII expression.
      These findings suggest that EGFRvIII expression may regulate phenotypic
      plasticity in ovarian cancer and thereby contribute to more aggressive disease.

PMID- 16788983
TI  - Quantitative and qualitative differences in protein expression between papillary
      thyroid carcinoma and normal thyroid tissue.
AB  - In order to better understand basic mechanisms of tumor development and identify
      potential new biomarkers, we have performed difference gel electrophoresis (DIGE)
      and peptide mass fingerprinting on pooled protein extracts from patients with
      papillary thyroid carcinoma (PTC) compared with matched normal thyroid tissue.
      Image analysis of DIGE gels comparing PTC and matched normal thyroid tissue
      protein indicated that 25% of the protein spots were differentially expressed at
      a 2.5-fold cutoff and 35% at two-fold. Comparison between two different pools of
      protein from normal thyroid tissues revealed differential protein expression of
      only 4% at 2.5-fold and 6% at two-fold cutoff. One hundred ninety-two protein
      spots were identified by MALDI-TOFMS, representing 90 distinct proteins.
      Excluding albumin, globins and thyroglobulin, imaging software determined 31
      proteins to be differentially expressed at the two-fold (or greater) level.
      Individual gel comparisons (PTC vs. matched normal) from five patients
      established that 15/31 (48%) of these proteins exhibited statistically
      significant differential expression. Previously identified molecular markers in
      this group of proteins include cathepsin B, cytokeratin 19, and galectin-3. Novel
      differentially expressed proteins include S100A6, moesin, HSP70 (BiP),
      peroxiredoxin 2, protein phosphatase 2, selenium binding protein 1, vitamin D
      binding protein, and proteins involved in mitochondrial function. The use of two
      dimensional gel electrophoresis (2DGE) revealed a significantly altered protein
      mass and/or pI in 10%-15% of proteins, suggesting alternatively spliced forms and
      other posttranslational modification of proteins revealed by this approach. We
      confirmed S100A6 as a potentially useful biomarker using immunohistochemical
      analysis (85% sensitivity and 69% specificity for distinguishing benign from
      malignant thyroid neoplasms). In summary, proteomic analysis of PTC using DIGE
      and mass spectrometry has confirmed several known biomarkers, uncovered novel
      potential biomarkers, and provided insights into global pathophysiologic changes
      in PTC. Many of the differences observed would not have been detected by genomic
      or other proteomic approaches.

PMID- 16788984
TI  - The comparison of pyrosequencing molecular Gram stain, culture, and conventional
      Gram stain for diagnosing orthopaedic infections.
AB  - We have developed a combined real-time PCR and pyrosequencing assay that
      successfully differentiated the vast majority of gram-positive and gram-negative
      bacteria when bacterial isolates were tested. The purpose of this study was to
      evaluate this assay on clinical specimens obtained from orthopedic surgeries, and
      to prospectively compare the results of "molecular Gram stain" with culture and
      conventional direct Gram stain. Forty-five surgical specimens were obtained from
      patients who underwent orthopedic surgery procedures. The DNA was extracted and a
      set of broad-range PCR primers that targeted a part of the 16S rDNA gene was used
      for pan-bacterial PCR. The amplicons were submitted for pyrosequencing and the
      resulting molecular Gram stain characteristics were recorded. Culture and direct
      Gram staining were performed using standard methods for all cases. Surgical
      specimens were reviewed histologically for all cases that had a discrepancy
      between culture and molecular results. There was an 86.7% (39/45) agreement
      between the traditional and molecular methods. In 12/14 (85.7%) culture-proven
      cases of bacterial infection, molecular Gram stain characteristics were in
      agreement with the culture results, while the conventional Gram stain result was
      in agreement only for five cases (35.7%). In the 31 culture negative cases, 27
      cases were also PCR negative, whereas 4 were PCR positive. Three of these were
      characterized as gram negative and one as gram positive by this molecular method.
      Molecular determination of the Gram stain characteristics of bacteria that cause
      orthopedic infections may be achieved, in most instances, by this method. Further
      studies are necessary to understand the clinical importance of PCR
      positive/culture-negative results.

PMID- 16788985
TI  - Novel explant model to study mechanotransduction and cell-cell communication.
AB  - To understand in situ behavior of osteocytes, we characterized a model of
      osteocytes in their native bone matrix and demonstrated real-time biologic
      activity of osteocytes while bending the bone matrix. Using 43 male Sprague
      Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral
      implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen
      specimens were used to determine bone volume density (BV/TV), volumetric bone
      mineral density (BMD) and histology for different implantation periods. Osteocyte
      viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured
      explants. Confocal microscopy was used to assess tracer diffusion in three
      explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to
      12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%,
      respectively. They were significantly and highly correlated. Tissues were
      uniformly intramembranous and all bone cell types were present. Explants
      maintained LDH activity through culture day 8. Diffusion at 200 microM was
      limited to 1,209 Da. Explants appeared capable of reproducing complex bone
      biology. This model may be useful in understanding osteocyte mechanotransduction
      in the context of a physiologically relevant bone matrix.

PMID- 16788986
TI  - High concentration and bioactivity of vancomycin and aztreonam eluted from
      Simplex cement spacers in two-stage revision of infected hip implants: a study of
      46 patients at an average follow-up of 107 days.
AB  - This study investigated the release of antibiotics in vivo, from an articulating
      polymethylmethacrylate (PMMA) spacer used in two-stage revision arthroplasty of
      infected hip implants. Forty-six patients who underwent two-stage revision hip
      arthroplasty for infections were managed with an interim PMMA spacer loaded with
      a high dose of vancomycin and aztreonam. Serum and aliquots of drainage collected
      after the first-stage surgery, and joint fluid obtained at the time of the second
      stage surgery were analyzed for antibiotic concentrations by high performance
      liquid chromatography and bioactivity by tube dilution bioassay. Following
      implantation, the highest levels of antibiotics were measured in aliquots of
      drainage on the first day (vancomycin: 1538.0 +/- 243.6 microg/mL; aztreonam:
      1003.5 +/- 323.5 microg/mL), decreasing to 571.9 +/- 169.4 microg/mL for
      vancomycin and 313.6 +/- 88.3 microg/mL for aztreonam after 7 days. Antibiotic
      concentrations in serum were very low (vancomycin: 0.58 +/- 0.2 microg/mL, range:
      0.1-1.6 microg/mL; aztreonam: 0.46 +/- 0.3 microg/mL, range: 0.1-0.9 microg/mL at
      24 h) and there was no systemic adverse effect. At a mean 107 days after the
      first-stage surgery, the concentrations of antibiotics in joint fluid were well
      above the minimal inhibitory concentration of most common microorganisms. The
      released antibiotics were bioactive against the test organisms. Based on the
      observed results, we confirmed the safety and effectiveness of in vivo drug
      delivery from antibiotic-impregnated PMMA hip spacers.

PMID- 16788987
TI  - In vivo molecular imaging of adenoviral versus lentiviral gene therapy in two
      bone formation models.
AB  - Regional gene therapy techniques are promising methods to enhance bone formation
      in large bone defects that would be difficult to treat with allograft or
      autograft bone stock. In this study, we compared in vivo temporal expression
      patterns of adenoviral- and lentiviral-mediated gene therapy in two bone
      formation models. Primary rat bone marrow cells (RBMC) were transduced with
      lentiviral or adenoviral vectors containing luciferase (Luc) or BMP-2 cDNA, or
      cotransduced with vectors containing Luc and bone morphogenetic protein 2 (BMP
      2). In vitro protein production was determined with luciferase assay or ELISA
      (for BMP-2 production) weekly for 12 weeks. Two bone formation models were used -
      a hind limb muscle pouch or radial defect -- in SCID mice. A cooled charged
      coupled device (CCD) camera was used to image in vivo luciferase expression
      weekly for 12 weeks. In vitro, adenoviral expression of BMP-2 and luciferase was
      detected by ELISA or luciferase assay, respectively, for 4 weeks. Lentiviral
      expression of BMP-2 and luciferase was sustained in culture for 3 months. Using
      the CCD camera, we found that adenoviral vectors expressed luciferase expression
      for up to 21 days, but lentiviral vectors expressed target gene expression for 3
      months in vivo in both bone formation models. There was no detectable difference
      in the amount of bone formed between the adenoviral and lentiviral groups.
      Lentiviral-mediated delivery of BMP-2 can induce long term in vitro and in vivo
      gene expression, which may be beneficial when developing tissue engineering
      strategies to heal large bone defects or defects with a compromised biologic
      environment.

PMID- 16788988
TI  - In vivo cyclic axial compression affects bone healing in the mouse tibia.
AB  - Abundant evidence exists that fracture healing can be influenced by mechanical
      loading. However, the specific loading parameters that are osteogenic remain
      unknown. We hypothesized that the bone healing response in mouse tibial
      osteotomies would be different with a short delay before loading compared to
      immediate load application, as well as with higher and lower load magnitudes
      applied. Eighty 12-week-old mice underwent osteotomy of the left tibia followed
      by intramedullary nailing. Mice were divided into six groups based on days
      delayed until application of load (0 days or 4 days) and amplitude of cyclic load
      (0.5N, 1N, or 2N). Loading regimens were applied at 1 Hz for 100 cycles per day,
      5 days per week for 2 weeks, using an external device that applied axial
      compression to the tibia. Bone healing was assessed by both microcomputed
      tomography (CT) and four-point bend testing. A short delay followed by cyclic
      application of a relatively low load led to improved fracture healing, as
      determined by increased callus strength, but this enhancement disappeared as load
      amplitudes increased. Load initiation immediately following fracture inhibited
      healing, regardless of the magnitude of load applied. MicroCT measurements of
      calluses in the early healing stage did not predict the mechanical strength of
      the fractures. These findings confirm that controlled, noninvasive cyclic loading
      can improve the strength of healing callus. However, application of load
      immediately after fracture appears to be detrimental to healing. Load magnitude
      also plays a critical role, and must be taken into account in future studies and
      clinical applications. As the loading parameters necessary to enhance fracture
      healing become refined, external compression may be used as a potent stimulus for
      treating fractures with decreased biological capacity.

PMID- 16788989
TI  - Age-related expression of molecular regulators of hypertrophy and maturation in
      articular cartilage.
AB  - The purpose of this study was to determine changes in the expression of
      regulatory molecules in normal equine articular cartilage throughout development
      up to 18 months of age. The hypothesis was that expression of these regulatory
      molecules would decrease from birth to postpubescence. Cartilage was harvested
      from normal femoropatellar or scapulohumeral joints from 34 fresh horse cadavers.
      Horses were placed in four age groups [prenatal (n = 5); prepubertal, 0-6 months
      (n = 11); pubertal, 7-14 months (n = 13); and postpubertal, 15-18 months (n =
      5)]. Indian hedgehog (Ihh), Gli1, Gli3, Patched1 (Ptc1), Smoothened (Smo),
      Noggin, bone morphogenetic protein-6 (BMP-6), BMP-2, parathyroid hormone-related
      peptide (PTHrP), and PTH/PTHrP receptor mRNA expression levels were evaluated by
      real-time quantitative PCR. Spatial tissue mRNA and protein expression was
      determined by in situ hybridization and immunohistochemistry. The expression of
      PTHrP decreased (p = 0.002) in the pubertal group, while PTH/PTHrP receptor
      expression significantly increased (p = 0.001). No significant difference was
      found between groups for Ihh (p = 0.6) or Smo (p = 0.3) expression. In contrast,
      there was significantly increased expression of Ptc1 (p = 0.006), Gli1 (p =
      0.04), and Gli3 (p = 0.007) in the pubertal group, and Gli3 (p = 0.007) remained
      elevated in the postpubertal group. The expression of BMP-6 significantly
      increased from prenatal to postnatal groups (p = 0.03) while BMP-2 expression
      increased during puberty and postpuberty (p = 0.03). The changes in expression of
      hedgehog and BMP signaling molecules in articular cartilage during postnatal
      development have not been shown previously. The increased expression of hedgehog
      receptor and transcription factors during puberty may indicate maturation of the
      deep articular layer during this time period.

PMID- 16788990
TI  - Microradiography as a tool to detect heavy metal uptake in plants for
      phytoremediation applications.
AB  - In this paper, an application of contact microradiography with soft X-rays for
      detecting the uptake site of heavy metal in the whole plant leaves is
      investigated. The X-ray source is a laser-plasma one based on an Nd:glass laser.
      The soft X-ray radiation emitted from the plasma laser targets of magnesium,
      iron, and copper can be strongly absorbed in the leaves' regions rich in iron,
      magnesium, and copper. This absorbance could point to structures in the leaves
      where these heavy elements are found. In this work, leaves treated with copper
      sulfate diluted in water at 1, 2, and 5% were imaged by using a copper target, in
      order to evaluate differences with untreated control leaves. Our results showed
      that this methodology highlighted the presence of copper in the treated leaves.
      This new methodology should detect heavy element pollutants inside plants and it
      should also be a useful analytic tool in phytoremediation studies.

PMID- 16788991
TI  - Quantitative study of Xanthosoma violaceum leaf surfaces using RIMAPS and
      variogram techniques.
AB  - Two new imaging techniques (rotated image with maximum averaged power spectrum
      (RIMAPS) and variogram) are presented for the study and description of leaf
      surfaces. Xanthosoma violaceum was analyzed to illustrate the characteristics of
      both techniques. Both techniques produce a quantitative description of leaf
      surface topography. RIMAPS combines digitized images rotation with Fourier
      transform, and it is used to detect patterns orientation and characteristics of
      surface topography. Variogram relates the mathematical variance of a surface with
      the area of the sample window observed. It gives the typical scale lengths of the
      surface patterns. RIMAPS detects the morphological variations of the surface
      topography pattern between fresh and dried (herbarium) samples of the leaf. The
      variogram method finds the characteristic dimensions of the leaf microstructure,
      i.e., cell length, papillae diameter, etc., showing that there are not
      significant differences between dry and fresh samples. The results obtained show
      the robustness of RIMAPS and variogram analyses to detect, distinguish, and
      characterize leaf surfaces, as well as give scale lengths. Both techniques are
      tools for the biologist to study variations of the leaf surface when different
      patterns are present. The use of RIMAPS and variogram opens a wide spectrum of
      possibilities by providing a systematic, quantitative description of the leaf
      surface topography.

PMID- 16788992
TI  - A dual tyrosine-leucine motif mediates myelin protein P0 targeting in MDCK cells.
AB  - Differential targeting of myelin proteins to multiple, biochemically and
      functionally distinct Schwann cell plasma membrane domains is essential for
      myelin formation. In this study, we investigated whether the myelin protein P0
      contains targeting signals using Madin-Darby canine kidney (MDCK) cells. By
      confocal microscopy, P0 was localized to MDCK cell basolateral membranes. C
      terminal deletion resulted in apical accumulation, and stepwise deletions defined
      a 15-mer region that was required for basolateral targeting. Alanine
      substitutions within this region identified the YAML sequence as a functional
      tyrosine-based targeting signal, with the ML sequence serving as a secondary
      leucine-based signal. Replacement of the P0 ectodomain with green fluorescent
      protein altered the distribution of constructs lacking the YAML signal.
      Coexpression of the myelin-associated glycoprotein did not alter P0 distribution
      in MDCK cells. The results indicate that P0 contains a hierarchy of targeting
      signals, which may contribute to P0 localization in myelinating Schwann cells and
      the pathogenesis in human disease.

PMID- 16788993
TI  - Potential for assessing quality of protein structure based on contact number
      prediction.
AB  - We developed a novel knowledge-based residue environment potential for assessing
      the quality of protein structures in protein structure prediction. The potential
      uses the contact number of residues in a protein structure and the absolute
      contact number of residues predicted from its amino acid sequence using a new
      prediction method based on a support vector regression (SVR). The contact number
      of an amino acid residue in a protein structure is defined by the number of
      residues around a given residue. First, the contact number of each residue is
      predicted using SVR from an amino acid sequence of a target protein. Then, the
      potential of the protein structure is calculated from the probability
      distribution of the native contact numbers corresponding to the predicted ones.
      The performance of this potential is compared with other score functions using
      decoy structures to identify both native structure from other structures and near
      native structures from nonnative structures. This potential improves not only the
      ability to identify native structures from other structures but also the ability
      to discriminate near-native structures from nonnative structures.

PMID- 16788994
TI  - Evolution of arthropod visual systems: development of the eyes and central visual
      pathways in the horseshoe crab Limulus polyphemus Linnaeus, 1758 (Chelicerata,
      Xiphosura).
AB  - Despite ongoing interest into the architecture, biochemistry, and physiology of
      the visual systems of the xiphosuran Limulus polyphemus, their ontogenetic
      aspects have received little attention. Thus, we explored the development of the
      lateral eyes and associated neuropils in late embryos and larvae of these
      animals. The first external evidence of the lateral eyes was the appearance of
      white pigment spots-guanophores associated with the rudimentary photoreceptors-on
      the dorsolateral side of the late embryos, suggesting that these embryos can
      perceive light. The first brown pigment emerges in the eyes during the last
      (third) embryonic molt to the trilobite stage. However, ommatidia develop from
      this field of pigment toward the end of the larval trilobite stage so that the
      young larvae at hatching do not have object recognition. Double staining with the
      proliferation marker bromodeoxyuridine (BrdU) and an antibody against L.
      polyphemus myosin III, which is concentrated in photoreceptors of this species,
      confirmed previous reports that, in the trilobite larvae, new cellular material
      is added to the eye field from an anteriorly located proliferation zone. Pulse
      chase experiments indicated that these new cells differentiate into new
      ommatidia. Examining larval eyes labeled for opsin showed that the new ommatidia
      become organized into irregular rows that give the eye field a triangular
      appearance. Within the eye field, the ommatidia are arranged in an imperfect
      hexagonal array. Myosin III immunoreactivity in trilobite larvae also revealed
      the architecture of the central visual pathways associated with the median eye
      complex and the lateral eyes. Double labeling with myosin III and BrdU showed
      that neurogenesis persists in the larval brain and suggested that new neurons of
      both the lamina and the medulla originate from a single common proliferation
      zone. These data are compared with eye development in Drosophila melanogaster and
      are discussed with regard to new ideas on eye evolution in the Euarthropoda.

PMID- 16788995
TI  - Exploring the links between posttraumatic stress disorder and social support:
      processes and potential research avenues.
AB  - Social support after a traumatic event is linked to posttraumatic stress disorder
      (PTSD). However, little is known about the ways in which social support
      influences the adaptation to trauma and development of PTSD. The aim of the
      present article is threefold: to outline the various processes by which social
      support is linked to PTSD, to review the most relevant research in the field, and
      to suggest potential future research.

PMID- 16788996
TI  - Alexithymia and PTSD symptoms in urban police officers: cross-sectional and
      prospective findings.
AB  - The relationship of alexithymia to posttraumatic stress disorder (PTSD)
      symptomatology was examined cross-sectionally in 166 urban police officers
      surveyed between 1998 and 1999 and prospectively in 54 of these officers who
      participated in a follow-up survey after the September 11, 2001 (9/11) terrorist
      attacks. In cross-sectional analyses, alexithymia scores were positively
      associated with PTSD symptom levels and self-reported childhood emotional abuse-
      neglect, but not with cumulative level of critical incident exposure. Alexithymia
      scores accounted for 11.2% of the variance in PTSD symptoms prior to accounting
      for additional predictors, but did not retain significance in the final model. In
      prospective analyses, alexithymia scores significantly predicted 9/11-related
      PTSD symptom severity over and above pre-9/11 PTSD symptoms.

PMID- 16788997
TI  - Subjective distress from stressful events and high-risk behaviors as predictors
      of PTSD symptom severity in clients with severe mental illness.
AB  - Survey data collected from 257 community mental health center clients tested
      direct and indirect relationships among subjective distress associated with
      stressful/traumatic events and high-risk behaviors, substance abuse, and
      posttraumatic stress disorder (PTSD) symptoms. Structural equation modeling (SEM)
      revealed substantial direct effects of subjective distress associated with
      lifetime physical and sexual abuse on PTSD symptom severity. Subjective distress
      related to high-risk behaviors (e.g., suicide attempts) mediated subjective
      distress and PTSD symptom severity. Subjective distress from physical and sexual
      abuse was also strongly related to problem drinking. Adding gender to the model
      revealed greater subjective distress from physical and sexual abuse for women and
      greater drinking problems for men. Otherwise, gender had little effect on the
      model overall.

PMID- 16788998
TI  - Alcohol problems and posttraumatic stress disorder in female crime victims.
AB  - Comorbidity between alcohol use and posttraumatic stress disorder (PTSD) has been
      well documented. However, there are few longitudinal studies with acute trauma
      samples. The present study examined symptoms of alcohol use disorders (AUDs) and
      PTSD longitudinally after assault. Female sexual (n = 69) and physical assault
      victims (n = 39) were assessed 2 to 4 weeks and 3 months post trauma. Women who
      had lifetime AUD had higher intrusive and avoidance symptoms than those who did
      not have AUD. Women who had any alcohol problems had higher PTSD symptoms.
      Participants who had alcohol problems had the same pattern of symptom recovery as
      those who did not have alcohol problems but remained more symptomatic over the 3
      months. These findings suggest that early intervention strategies for women who
      have previous histories of alcohol problems and seek medical attention early post
      trauma may be indicated.

PMID- 16788999
TI  - Assessment of posttraumatic stress disorder in Cambodian refugees using the
      Clinician-Administered PTSD Scale: psychometric properties and symptom severity.
AB  - Posttraumatic stress disorder (PTSD) symptoms were assessed by using the
      Clinician-Administered PTSD Scale (CAPS) in a consecutive sample of Cambodian
      refugees attending a psychiatric clinic in the United States. Psychometric
      properties of the translated CAPS and severity of PTSD-related symptoms were
      examined. The CAPS demonstrated adequate psychometric properties, including
      coefficient alpha (.92) and item-total correlations (.48-.85). Of the sample 56%
      (101/179) met Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition, criteria for current PTSD. Those patients who met criteria for current
      PTSD had significantly higher CAPS total scores (M = 65.3, SD = 18.1) than those
      who did not meet the criteria (M = 13.9, SD = 16.7).

PMID- 16789000
TI  - Post-tsunami stress: a study of posttraumatic stress disorder in children living
      in three severely affected regions in Sri Lanka.
AB  - At 3 to 4 weeks after the December 2004 tsunami disaster we assessed symptoms of
      posttraumatic stress disorder (PTSD) in 264 children who lived in severely
      affected coastal communities in Manadkadu (northern coast), Kosgoda (western
      coast), and Galle (southern coast) in Sri Lanka. The prevalence rate of tsunami
      related posttraumatic stress disorder (PTSD) (ignoring the time criterion) ranged
      between 14% and 39% and an additional 5% to 8% had PTSD unrelated to the tsunami.
      The PTSD symptoms were explained by the severity of the trauma exposure and
      family loss, as well as previous traumatic events. The results confirm the
      relevance of the individual history of traumatic events for the genesis of PTSD
      and indicate a high need of mental health assistance among the tsunami-affected
      children in Sri Lanka.

PMID- 16789001
TI  - Initial physiological responses and perceived hyperarousal predict subsequent
      emotional numbing in pediatric injury patients.
AB  - The present study tested the hypothesis that acute posttraumatic hyperarousal
      would lead to the development of emotional numbing (EN) symptoms in a pediatric
      injury population. Eighty-two youths aged 8-18 years were recruited from the
      emergency department of a Midwestern children's hospital. Heart rate was recorded
      from emergency medical services reports and a 12-hour urine collection was
      initiated upon admission. Six weeks and 6 months later, depression and PTSD
      symptoms were assessed. Initial heart rate and urinary cortisol levels predicted
      6-week and 6-month EN after controlling for concurrent depression, avoidance, and
      reexperiencing symptoms and 6-week hyperarousal symptoms. These findings provide
      empirical support for prior hypotheses concerning the development of PTSD
      symptoms over time.

PMID- 16789002
TI  - The impact of posttraumatic stress disorder on quality of life and health service
      utilization among veterans who have schizophrenia.
AB  - The present study examined the impact of comorbid posttraumatic stress disorder
      (PTSD) on health-related quality of life and objective measures of health service
      utilization in 165 male veterans who have primary schizophrenia. Comorbid PTSD
      was assessed with the PTSD Checklist. Comorbid PTSD was significantly associated
      with decreased quality of life and increased medical service utilization,
      including increased psychiatric hospitalization and increased outpatient physical
      health visits, even after controlling for other clinical and demographic
      variables among this sample of patients who had primary schizophrenia. Veterans
      who have schizophrenia should be screened carefully for exposure to trauma and
      posttraumatic stress disorder.

PMID- 16789003
TI  - Posttraumatic stress disorder symptoms in treatment-seeking pathological
      gamblers.
AB  - Little is known about posttraumatic stress disorder (PTSD) among pathological
      gamblers (PGs), even though the two disorders share several clinical
      characteristics. We examined the relationship between pathological gambling and
      PTSD on measures of gambling disorder severity, experience of specific traumas,
      psychiatric symptoms, impulsivity, and dissociation. A total of 149 treatment
      seeking PGs were surveyed. Participants were divided into two groups on the basis
      of their score on the PTSD Checklist (Weathers, Litz, Herman, Huska, & Keane,
      1993). Thirty-four percent (n = 51) reported a high frequency of PTSD symptoms.
      Participants who had high scores reported greater lifetime gambling severity,
      psychiatric symptom severity, impulsivity, and dissociation than participants who
      had low PTSD symptom scores. These findings point to a need for more assessment
      and research about PTSD in PGs.

PMID- 16789004
TI  - Differential experiences during the holocaust and suicidal ideation in older
      adults in treatment for depression.
AB  - Data were used on 275 Jewish individuals aged 50 and older in outpatient
      treatment for depression in this retrospective cross-sectional study. Holocaust
      survivors who were in work camps, in ghettos, or in hiding (HS-WGH) and holocaust
      survivors who were in concentration camps (HS-CC) were more likely to suffer
      posttraumatic stress disorder compared to other survivors (HS-OT) and controls.
      The HS-WGH and HS-CC groups had at least a threefold greater odds of suicidal
      ideation compared to controls. Suicidal ideation rates did not differ
      significantly between HS-OT group and controls. Among survivors, HS-WGH had a
      threefold greater odds of suicidal ideation compared to HS-OT. The results are
      applicable to survivors of similar atrocities and show that differing types and
      severities of traumatic experiences have important implications for treatment
      planning.

PMID- 16789005
TI  - A pilot study of behavioral activation for veterans with posttraumatic stress
      disorder.
AB  - A pilot study was conducted to investigate the feasibility and effectiveness of
      behavioral activation (BA) therapy for veterans with posttraumatic stress
      disorder (PTSD). Eleven veterans seeking treatment at a Veterans Administration
      outpatient PTSD clinic were enrolled in the study protocol, consisting of 16
      weekly individual sessions of BA. Nine veterans completed the protocol, one
      participant completed 15 sessions, and one dropped out after one session.
      Clinician-rated PTSD symptom severity showed significant pre- to posttreatment
      improvement and was associated with a moderate effect size. A number of
      participants also were improved on measures of depression and quality of life,
      but changes did not reach statistical significance. Findings suggest that BA is a
      well-tolerated, potentially beneficial intervention for veterans with chronic
      symptoms of PTSD.

PMID- 16789006
TI  - A model of care for managing traumatic psychological injury in a workers'
      compensation context.
AB  - Work-related traumatic psychological injuries are a significant health problem
      that can result in distress and disability. To improve outcomes following a
      workplace trauma, the Workers' Compensation Board of Alberta (WCB-AB) has
      developed and implemented an evidence-based care model (CM) to assist its staff
      to manage these claims. A CM acts as a disability management "road map" that
      illustrates typical recovery patterns, treatment best practices, and checkpoints
      where decisions for further service provision can be made. The model was
      developed from a recent literature review, and the opinions of local and
      international experts in the field of traumatic psychological injury. A formal
      evaluation of the effectiveness of this model is being planned.

PMID- 16789008
TI  - Studies on TAQ1 polymorphism in the 3'untranslated region of IL-12P40 gene in HCV
      patients infected predominantly with genotype 3.
AB  - Host immunity plays an important role in viral persistence and progression of
      liver disease in HCV infected patients. IL-12 induces production of IFN-gamma, a
      potent antiviral agent. IL-12 comprises two subunits; IL-p35 and IL-12p40, which
      are encoded by two different genes located on chromosome 3 and 5, respectively.
      Single nucleotide polymorphism at A1188C in the 3'UTR of IL-12p40 gene is
      associated with immune mediated diseases. Association of IL-12p40 A1188C
      polymorphism with the outcome of HCV infection was investigated in this study.
      Two hundred and fifty three histologically proven chronic hepatitis C patients
      (43 +/- 13 years, male:female: 185:68) and 380 matched controls were included.
      Genotyping was performed by RFLP and confirmed by direct sequencing. To assess
      correlation of immune gene polymorphism with severity of HCV-related liver
      disease, patients were divided into those with fibrosis score of < or = 2 (mild)
      or > 2 (severe), and histological activity index (HAI) of = 5 (mild) or > 5
      (severe). The distribution of A/A, A/C or C/C alleles in the controls was
      comparable to the patients. The distribution of C/C allele was significantly more
      common in patients with mild as compared to severe fibrosis (23.7% vs. 6.25%, P =
      0.004). No significant difference was observed for any of the genetic markers
      with HAI or with normal or raised alanine aminotransferase (ALT). These results
      show that the C/C allele of IL-12p40 gene could render genetic protection against
      development of severe liver disease in patients infected with HCV.

PMID- 16789007
TI  - Distinct changing profiles of hepatitis A and E virus infection among patients
      with acute hepatitis, patients on maintenance hemodialysis and healthy
      individuals in Japan.
AB  - To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E
      virus (HEV) infections in Japan, the prevalence of clinical or subclinical HAV
      and HEV infections was investigated serologically and molecularly among 128
      consecutive patients (age, mean +/- standard deviation, 37.5 +/- 14.7 years) who
      contracted acute hepatitis between 1989 and 2005 in a city hospital, and among
      416 hemodialysis patients (60.1 +/- 12.6 years) and 266 medical staff members
      (34.6 +/- 11.4 years) at the same hospital, using stored periodic serum samples
      collected since the start of hemodialysis or employment, respectively. Between
      1989 and 1995, among 93 patients with acute hepatitis, 51 (54.8%) were diagnosed
      with hepatitis A and only one patient with hepatitis E. Between 1996 and 2005,
      however, among 35 patients, only 3 (8.6%) were diagnosed with hepatitis A and 2
      (5.7%) with hepatitis E. Although subclinical HEV infection was recognized in
      four hemodialysis patients (one each in 1979, 1980, 1988, and 2003) and two
      medical staff members (1978 and 2003) in previous studies, none of the 191
      hemodialysis patients who had been negative for anti-HAV at the start of
      hemodialysis contracted HAV infection during the observation period of 7.6 +/-
      6.4 years. Only one (0.4%) of the 246 medical staff members who had been negative
      for anti-HAV at the start of employment acquired hepatitis A during the
      observation period of 7.9 +/- 8.0 years: none had subclinical HAV infection.
      Clinical or subclinical HEV infection has occurred rarely during the last three
      decades, while HAV infection has markedly decreased at least since 1996.

PMID- 16789009
TI  - Distribution of Epstein-Barr virus genotypes in throat washings, sera, peripheral
      blood lymphocytes and in EBV positive tumor biopsies from Slovenian patients with
      nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a malignancy closely associated with Epstein
      Barr virus (EBV). It is prevalent among the Chinese of Southern China, whereas
      outside China, the position seems to be different. The aim of this study was to
      determine the distribution of EBV genotypes in the patients with NPC in Slovenia,
      which is a nonendemic area. Detection of EBV was undertaken by testing the throat
      washes, sera, peripheral blood lymphocytes (PBLs), and biopsies of primary tumors
      of 48 patients with NPC in Slovenia. The sera of 20 patients with serologically
      confirmed primary EBV infection served as a control clinical material. The
      analysis of genotypes was carried out on three regions of EBV genome; BamHI WYH,
      BamHI I, and BamHI F, using the polymerase chain reaction (PCR) and restriction
      fragment length polymorphism (RFLP). The results show that, in Slovenia, the
      predominant combination of EBV genotypes based on the differences in the three
      genomic regions is ADF. This combination was found in 56 out of 103 different EBV
      positive clinical samples (throat washes, sera, PBLs, and tumor biopsies) of
      patients with NPC and in 15 out of 17 sera of patients with primary EBV
      infection. Very low number of genotypes C and f were detected, in spite of the
      fact that these two genotypes were considered to be associated with the
      development and/or maintenance of NPC in Southern China. Genotype f was found in
      only two tumor biopsies; in all other clinical samples (throat washes, sera and
      PBLs), genotype F was detected. Genotype C was proven in 31/103 clinical samples,
      with the highest percentage in tumor biopsies (37.5%). As in the NPC patients
      from other countries (Alaska is an exception), genotype A was predominant and was
      detected in 86/103 clinical samples. Genotype B was found in 15 clinical samples
      of patients with NPC and in 3 the two genotypes A and B were found. In comparison
      to China, these results show different EBV genotypes distribution. It seems that
      the genetic disposition of human population is an important factor that may
      contribute to different susceptibility for specific EBV genotypes.

PMID- 16789010
TI  - Association of the G4 rotavirus genotype with gastroenteritis in adults.
AB  - Rotavirus is the most common etiological cause of acute viral gastroenteritis in
      infants and young children worldwide, yet its role in the adult population is
      less well understood. We have recently identified rotavirus as the causative
      agent of severe diarrhea in adults, specifically in two gastroenteritis outbreaks
      in separate care for the elderly homes. Strain typing has shown the continued
      presence of P[8]G1, the emergence of P[8]G9, and the reemergence of P[8]G4. A
      total of 26 community cases and 6 outbreak cases of rotavirus infection, positive
      via a molecular screening assay, were subsequently amplified using VP4 and VP7
      specific primers (Con2/Con3 and 1A/1B primer sets, respectively). The age range
      of patients investigated was from <1 year to 89 years. The resulting PCR products
      were cloned into TOPO10 PCR IV vector and sequenced to give the P- and G-type
      accordingly. All sequence data were subjected to BLAST analysis. Three different
      rotavirus types P[8]G1, P[8]G4, and P[8]G9 were identified. Types P[8]G1 and
      P[8]G9 were identified as circulating within the community, whereas the third
      type P[8]G4 was identified only in an elderly care outbreak. The identification
      of G9 rotaviruses supports evidence of emergence of the genotype on a global
      scale.

PMID- 16789011
TI  - Changes in viral loads of lamivudine-resistant mutants and evolution of HBV
      sequences during adefovir dipivoxil therapy.
AB  - The addition of adefovir dipivoxil (ADV) to ongoing lamivudine therapy is
      effective against lamivudine-resistant virus in patients with hepatitis B virus
      (HBV) infection. We studied 39 patients who received ADV added to lamivudine for
      breakthrough hepatitis. We determined early viral changes (12 weeks) in YMDD
      mutants (rtM204I [YIDD sequence], rtM204V [YVDD]) and rtL180M in all 39 patients
      as well as amino acid changes in the polymerase reverse transcriptase (rt) region
      and precore/core promoter mutations in 15 patients who received long-term
      treatment (more than 1 year). Changes in rtM204I and rtL180M viral loads were
      greater than that of the rtM204V, albeit statistically insignificant. Moreover,
      the greatest change in viral load was seen for rtM204I without hepatitis B e
      antigen (HBeAg). The precore mutant was replaced with wild-type virus in three of
      eight patients after 1 year of added ADV therapy. Compared to baseline with
      lamivudine therapy only, new amino acid mutations were seen in the rt region at
      baseline with ADV in seven patients. At 1 year after ADV coadministration, the
      YMDD motif was replaced with wild-type (rt204M) in two patients, in whom
      mutations were fewer and of a different type. We conclude that the rtM204I may be
      more sensitive to ADV in vivo. ADV tended to select wild-type virus from precore
      mutants. Moreover, viruses that were wild-type in the rt region reappeared after
      1 year of ADV coadministration in some patients.

PMID- 16789012
TI  - Basal core promoter, precore region mutations of HBV and their association with e
      antigen, genotype, and severity of liver disease in patients with chronic
      hepatitis B in India.
AB  - Spontaneous mutations of hepatitis B virus (HBV) could influence the severity of
      liver disease. Since the basal core promoter (BCP) and the precore (Pc) regions
      are important for viral replication, these regions were examined for naturally
      occurring mutations and were correlated with the genotype, e antigen status, and
      severity of liver disease. In 82 patients with histologically confirmed chronic
      hepatitis B, the BCP and Pc regions were sequenced and aligned with known wild
      type sequences. Sequence based HBV genotyping was done and HBV DNA was
      quantified. Thirty-three (40%) patients had decompensated chronic liver disease
      and the remaining patients had chronic hepatitis B. Forty-six (56%) patients were
      HBeAg positive. HBV genotype A was found in 28%, D in 65%, and B/C in 7.3%. The
      Pc G1896A mutation was more common in HBeAg-negative (33% vs. 2%, P < 0.01)
      patients and was genotype D specific. The Pc G1862T mutation was detected more
      often in HBeAg-positive than HBeAg-negative (37% vs. 11%, P < 0.01) patients and
      was genotype A specific (P < 0.01). BCP mutations at the 1,762/64 nucleotide
      positions were common in HBeAg negative than positive (36% vs. 13%, P < 0.05) and
      were equally common in different genotypes. TA 1-3 region mutations of the BCP
      were significantly higher in HBeAg-negative as compared to HBeAg-positive
      patients (78% vs. 26%, P < 0.01). BCP mutations had significantly higher HBV DNA
      levels. It is concluded that Pc G1862T mutant is Genotype A-specific but is not
      always associated with e antigen. The TA 1-3 rich mutations of BCP region are
      also associated with the absence of e antigen in Indian patients.

PMID- 16789013
TI  - Genetic variation of NSP1 and NSP4 genes among serotype G9 rotaviruses causing
      hospitalization of children in Melbourne, Australia, 1997-2002.
AB  - Serotype G9 rotaviruses have emerged as one of the leading causes of
      gastroenteritis in children worldwide. We examined 29 representative G9 rotavirus
      isolates from a 6-year collection (1997-2002) and determined the level of
      variation in genes encoding non-structural proteins, NSP1 and NSP4. Northern
      hybridization analysis with a whole genome probe derived from the prototype G9
      strain, F45, revealed that the NSP1 gene (gene 5) of two isolates (R1 and R14)
      did not exhibit significant homology. Complementary DNA probes of R1 and R14
      genes 5 were used in Northern blot hybridization and indicated the presence of at
      least two gene 5 alleles among Melbourne G9 rotaviruses. Nucleotide sequence
      analysis revealed that isolates carrying the R14 gene 5 shared 94-98% sequence
      identities with one another, while sequence identity to R1 was 78%. Surprisingly,
      R1 displayed 96% nucleotide identity with the prototype serotype G1 strain, Wa.
      The detection of different alleles of NSP1 genes prompted us to investigate the
      level of variation in another non-structural protein, NSP4, a multifunctional
      protein and the first viral-encoded enterotoxin. Phylogenetic analysis indicated
      that while all isolates clustered into one group containing the Wa NSP4 allele
      (genotype 1), isolate R1 was most closely related to Wa. This study reveals new
      information about the diversity of non-structural proteins of G9 rotaviruses.

PMID- 16789014
TI  - Optimized virus disruption improves detection of HIV-1 p24 in particles and
      uncovers a p24 reactivity in patients with undetectable HIV-1 RNA under long-term
      HAART.
AB  - HIV-1 p24 antigen (p24) measurement by signal amplification-boosted ELISA of heat
      denatured plasma is being evaluated as an alternative to HIV-1 RNA quantitation
      in resource-poor settings. Some observations suggested that virion-associated p24
      is suboptimally detected using Triton X-100-based virus dissociation buffer (kit
      buffer). A new reagent (SNCR buffer) containing both denaturing and non
      denaturing detergents was therefore developed and evaluated. The SNCR buffer
      increased the measured p24 concentration about 1.5- to 3-fold in HIV-negative
      plasma reconstituted with purified HIV-1 particles, while not increasing the
      background. Among 127 samples of HIV-1-positive patients with moderate to high
      concentrations of HIV-1 RNA the increase was about threefold across the entire
      concentration range (P < 0.0001). Specificity before neutralization among
      prospectively tested clinical samples ruled HIV-negative was 828 of 845 (98.0%)
      for the SNCR buffer and 464 of 479 (96.9%) for kit buffer. Specificity after
      confirmatory neutralization of reactive samples or a follow-up test was 100% with
      either buffer. Surprisingly, the SNCR buffer revealed a p24 reactivity in 115 of
      187 samples (61.5%) from adult patients exhibiting undetectable HIV-1 RNA below 5
      copies/ml for a duration of 6-30 months under HAART (3.7% with kit buffer). The
      rate of p24 reactivity in these patients did not decrease with duration of HAART.
      In conclusion, the SNCR buffer improves the detection of particle-associated HIV
      1 p24, thereby increasing the measured p24 concentration in samples with medium
      to high HIV-1 RNA. It also uncovers the presence of a p24 reactivity, whose
      identity remains to be determined, in a significant fraction of samples with
      undetectable HIV-1 RNA under long-term HAART.

PMID- 16789015
TI  - Molecular epidemiology of hepatitis B virus in the United Republic of Tanzania.
AB  - In the United Republic of Tanzania, 457 voluntary blood donors were enrolled in
      hepatitis B virus (HBV) serological screening; 4.8% (22/457) carried HBsAg, 13.6%
      (3/22) of whom were HBeAg-positive. The mean age among HBeAg-negative carriers
      was 31 years. HBV DNA was detectable in 81.8% (18/22), the mean level was 3.67
      (+/-1.77) log copies/ml. Genotype A was determined in 90.9% (20/22) and 18/20
      were classified into subgenotype Aa (Asia/Africa). The basal core promoter,
      precore and partial core nucleotide sequences were analyzed in the 18 strains;
      T1809/T1812 ("Kozak" sequence) and A/T1888 (encapsidation signal) variants were
      identified in 100% and 78%, respectively. The complete genome sequencing for one
      of the Tanzanian strains revealed no recombination. In conclusion, HBV
      seroprevalence is high among general population in Tanzania, and the HBV/Aa
      infection is predominant. The indicated tendency to early HBeAg seroconversion
      and declining of the viral load should be confirmed further in case-control
      studies.

PMID- 16789016
TI  - Detection of a hepatitis B surface antigen variant emerging in a patient with
      chronic lymphocytic leukaemia treated with fludarabine.
AB  - Fludarabine is used widely for the treatment of chronic lymphocytic leukaemia,
      but not as yet implicated in the emergence of hepatitis B surface antigen (HBsAg)
      variants following hepatitis B virus (HBV) reactivation. Such a variant was
      detected in a 78-year-old female who was HBsAg(-)/anti-HBc(+)/anti-HBs(+)/anti
      HBe(+), and with normal ALT levels, who developed HBV reactivation after
      fludarabine treatment. She had high HBV-DNA levels, and became positive for
      HBeAg, in the absence of detectable HBsAg. HBV-DNA was extracted from serum and
      the HBsAg encoding region of the genome was amplified by PCR, followed by cloning
      and sequencing. The HBV strain appeared to be subtype adw, but had higher
      nucleotide homology with ayw than adw isolates, supported further by phylogenetic
      tree analysis. Amino-acid sequence comparisons over the alpha determinant region
      revealed the following substitutions: C124N, G130R, and N146S. There were also
      unique substitutions outside the alpha determinant. All these mutations appeared
      to have a profound effect on the antigenicity of this region, which resulted in
      failure to detect HBsAg by commercially available diagnostic assays. It is
      concluded that a surface variant emerged in an HBsAg(-)/anti-HBs(+) patient with
      chronic lymphocytic leukaemia following fludarabine treatment, with an
      unprecedented number of amino-acid substitutions in the alpha determinant region
      of HBsAg, including a subtype switch.

PMID- 16789017
TI  - Early decrease in circulating dendritic cells number after liver transplantation
      could favor hepatitis C virus recurrence.
AB  - Cirrhosis and hepatocarcinoma related to hepatitis C virus (HCV) lead to more
      than 30% of liver transplantations. Host- and virus-related mechanisms, involved
      in the recurrence of HCV infection of the liver graft, are not yet well known. A
      weak CD4+ T-cell response was shown to be involved in the outcome of re-infection
      but whether dendritic cell numbers are modified in patients transplanted for HCV
      related disease has never been evaluated. Eight transplanted patients for HCV
      related disease and eight non-HCV-infected transplanted controls were included.
      Blood plasmacytoid dendritic cells and myeloid dendritic cells were quantified
      before transplantation, at day 7 and 1 month after transplantation. Plasma
      interferon (IFN)-alpha and interleukin (IL)-12 were concomitantly measured. The
      results showed a significant decrease in the relative (P < 0.0001) and absolute
      (P = 0.0002) values of blood plasmacytoid dendritic cells at day 7 after
      transplantation when compared to the values obtained before transplantation,
      increasing again 1 month later, in both HCV-infected patients and controls. The
      same tendency was observed for myeloid dendritic cell relative values (P =
      0.0004) and plasma IL-12 (P < 0.05). IFN-alpha appeared to be less often
      detectable for HCV-infected patients. These results obtained on dendritic cell
      numbers could explain partially the early and systematic recurrence of HCV
      infection on the liver graft and contribute to better adapted therapeutic
      strategies.

PMID- 16789018
TI  - Validation of single real-time TaqMan PCR assay for the detection and
      quantitation of four major genotypes of hepatitis E virus in clinical specimens.
AB  - Since the characterization of the genome of the hepatitis E virus (HEV) in 1990,
      a large genetic diversity has been described. A single real-time reverse
      transcription (RT)-PCR assay with TaqMan technology has been validated which uses
      only one set of primers and probe within the ORF2 HEV region (nt 5207-5292) for
      the detection and quantification of the four major genotypes of HEV. This assay
      proved to be as efficient as the conventional RT-PCR methodology for the
      detection of HEV in clinical samples testing positive previously. The real-time
      RT-PCR and conventional RT-PCR were performed comparatively on 60 pairs of sera
      and stools collected during a recent outbreak of hepatitis E in Darfur. The real
      time RT-PCR assay was 10- to 100-fold sensitive than for conventional RT-PCR
      assays used in this study with a range quantitation from 1.8 x 10(1) to 7.2 x
      10(3) RNA copies/microl in clinical samples (serum and stools).

PMID- 16789019
TI  - Nipah virus RNA synthesis in cultured pig and human cells.
AB  - Nipah virus infection of porcine stable kidney cells (PS), human neuronal cells
      (SK-N-MC), human lung fibroblasts cells (MRC-5), and human monocytes (THP-1) were
      examined. Rapid progression of cytopathic effects (CPE) and cell death were noted
      in PS cell cultures treated with Nipah virus, followed by MRC-5, SK-N-MC, and THP
      1 cell cultures, in descending order of rapidity. Significant increase in the
      intracellular Nipah virus RNA occurred beginning at 24 hr PI in all the infected
      cells. Whereas, the extracellular release of Nipah virus RNA increased
      significantly beginning at 48 and 72 hr PI for the infected MRC-5 cells and PS
      cells, respectively. No significant release of extracellular Nipah virus RNA was
      detected from the Nipah virus-infected SK-N-MC and THP-1 cells. At its peak,
      approximately 6.6 log PFU/microl of extracellular Nipah virus RNA was released
      from the Nipah virus-infected PS cells, with at least a 100-fold less virus RNA
      was recorded in the Nipah virus-infected SK-N-MC and THP-1. Approximately 15.2%
      (+/-0.1%) of the released virus from the infected PS cell cultures was infectious
      in contrast to approximately 5.5% (+/-0.7%) from the infected SK-N-MC cells. The
      findings suggest that there are no differences in the capacity to support Nipah
      virus replication between pigs and humans in fully susceptible PS and MRC-5
      cells. However, there are differences between these cells and human neuronal
      cells and monocytes in the ability to support Nipah virus replication and virus
      release.

PMID- 16789020
TI  - Recombinant Newcastle Disease virus capsids displaying enterovirus 71 VP1
      fragment induce a strong immune response in rabbits.
AB  - The complete VP1 protein of EV71 was truncated into six segments and fused to the
      C-terminal ends of full-length nucleocapsid protein (NPfl) and truncated NP (NPt;
      lacks 20% amino acid residues from its C-terminal end) of newcastle disease virus
      (NDV). Western blot analysis using anti-VP1 rabbit serum showed that the N
      terminal region of the VP1 protein contains a major antigenic region. The
      recombinant proteins carrying the truncated VP1 protein, VP1(1-100), were
      expressed most efficiently in Escherichia coli as determined by Western blot
      analysis. Electron microscopic analysis of the purified recombinant protein, NPt
      VP(1-100) revealed that it predominantly self-assembled into intact ring-like
      structures whereas NPfl-VP(1-100) recombinant proteins showed disrupted ring-like
      formations. Rabbits immunized with the purified NPt-VP(1-100) and NPfl-VP(1-100)
      exhibited a strong immune response against the complete VP1 protein. The antisera
      of these recombinant proteins also reacted positively with authentic enterovirus
      71 and the closely related Coxsackievirus A16 when analyzed by an
      immunofluorescence assay suggesting their potential as immunological reagents for
      the detection of anti-enterovirus 71 antibodies in serum samples.

PMID- 16789021
TI  - Determination of HPV type 16 and 18 viral load in cervical smears of women
      referred to colposcopy.
AB  - It has been recognized that human papillomavirus infection is the major causal
      factor for high-grade cervical lesions. The aim of the study was to evaluate the
      relationship between HPV 16 and 18 viral loads and cervical status in different
      age strata. A duplex real time PCR method was devised to determine HPV 16 and 18
      viral load per million of human cells using an in house plasmidic construct as a
      standard of quantification. The 151 cervical scrapes were collected before
      colposcopic examination from either abnormal cervico-vaginal smear (group 1, 97
      patients) or from post treatment clinical follow-up (group 2, 54 patients). In
      women aged 30-40, the HPV16 viral loads were significantly higher in high-grade
      squamous intraepithelial lesion than in low-grade squamous intraepithelial lesion
      in both groups and HPV18 in group 1. In women aged 20-30 of group 1, high HPV
      viral load was associated in few cases with high-grade squamous intraepithelial
      lesion or low-grade squamous intraepithelial lesion, and surprisingly in some
      patients with normal cervix. HPV 16 and 18 viral loads are related to the
      severity of cervical lesion, and may be useful in the clinical management of
      cervical lesions. A specific follow-up may be useful for those with high viral
      load despite normal cervix.

PMID- 16789022
TI  - Case report: Hepatitis A preceding Guillain-Barre syndrome.
AB  - A case of acute hepatitis A with Guillain-Barre Syndrome subtype AMAN (acute
      motor axonal neuropathy) in a 17-year-old male is reported. Serum and
      cerebrospinal fluid were positive for anti-hepatitis A virus (HAV) IgM, IgG, and
      IgA. The onset of the syndrome was evident in week 3 of illness. The remarkably
      high titers of serum anti-HAV IgG appeared unique to a hepatitis A patient with
      the syndrome. Phylogenetic analysis of the HAV genome detected in the serum and
      feces revealed genotype IIIA, circulating commonly in Pune, western India.

PMID- 16789023
TI  - Molecular epidemiology of HIV-1 subtypes based on analysis of pol sequences in
      Slovenia, 1996-2005.
AB  - Various studies have demonstrated the increasing prevalence of non-B HIV-1
      subtypes in Western Europe. In contrast, knowledge about the molecular
      epidemiology of HIV-1 in Central and Eastern Europe is limited. The objective of
      present study was to investigate the HIV-1 molecular diversity as well as time
      trends in HIV-1 subtype distribution in Slovenia. A retrospective molecular
      epidemiological survey was conducted on a cohort representing 88% (131/149) of
      all HIV-1 infected patients diagnosed between January 1996 and June 2005. The
      study revealed that subtype B is a predominant HIV-1 subtype in Slovenia
      (110/131; 84%), although a relatively high proportion (21/131; 16%) of non-B
      subtypes was found. Among them, a high proportion of recombinant (10/21; 48%) and
      different unclassified strains (8/21; 38%) were identified. Non-B subtype viruses
      were predominant among heterosexuals (19/21; 90%) and subtype B viruses among men
      who have sex with men (84/110; 76%). Importantly, 86% (18/21) of patients
      infected with non-B subtypes were of Slovenian nationality. In contrast to
      Western European countries, a significant increase (P = 0.015) in the proportion
      of men who have sex with men was observed recently among newly diagnosed HIV-1
      infected patients in Slovenia.

PMID- 16789024
TI  - Complete genomic sequences for hepatitis C virus subtypes 6e and 6g isolated from
      Chinese patients with injection drug use and HIV-1 co-infection.
AB  - In one of our recent studies, two HCV genotype 6 variants were identified in
      patients from Hong Kong and Guangxi in southern China, with injection drug use
      and HIV-1 co-infection. We report the complete genomic sequences for these two
      variants: GX004 and HK6554. Their entire genome lengths were 9,468 and 9,462 nt;
      the 5' UTRs were 338 nt followed by single ORFs of 9,069 nt; the 3' UTRs were 61
      and 55 nt including 29 and 23 nt poly(U) tracks. Phylogenetic analysis using a
      maximum likelihood method showed that HK6554 was classified into subtype 6g and
      GX004 represented the first complete genome sequence for subtype 6e. Further
      analysis with reference sequences in three different genomic regions revealed
      that GX004 closely clustered with a group of subtype 6e variants, which were
      previously exclusively found in Vietnam and recently increasingly identified in
      injection drug users from the Guangxi province in southern China that borders
      Vietnam. This suggests that subtype 6e could become epidemic in southern China by
      network transmission among injection drug users.

PMID- 16789025
TI  - Detection of antibodies against human metapneumovirus by Western blot using
      recombinant nucleocapsid and matrix proteins.
AB  - Detection of antibodies against individual proteins of human metapneumovirus
      (hMPV) is important in the analysis of immune responses to hMPV. Specific
      antibodies against nucleocapsid (N) and matrix (M) proteins in 97 serum samples
      were tested by Western blot using recombinant N and M proteins of hMPV expressed
      in Escherichia coli. The results were compared with those of immunofluorescence
      assays (IFAs) based on hMPV-infected LLC-MK2 cells, which expressed the whole
      hMPV proteins. Thirty (61.2%) and 31 (63.3%) of 49 serum samples with titers of >
      or = 1:160 by IFA reacted with N and M proteins, respectively. Only 2 (4.2%) of
      11 serum samples with titers of 1:80 by IFA reacted with N and M proteins.
      Antibodies against N and M proteins were not detected in 37 serum samples with
      titers of < 1:40 by IFA. These results indicate that the antibodies against N and
      M proteins are highly specific (100%) but less sensitive (42.1%, N protein;
      40.8%, M protein) than those against whole proteins of hMPV detected by IFA. The
      reactivity of sera with the recombinant N protein and that with the recombinant M
      protein correlated well (correlation coefficient of 0.79), and the concordance of
      reactivities was 91% (kappa = 0.79). In summary, both recombinant N and M
      proteins of hMPV were antigenic, and the responses to N and M protein varied
      among patients. Therefore, Western blot using N and M proteins provide a useful
      tool for analysis of immune responses to hMPV.

PMID- 16789026
TI  - Detection of group a human rotavirus G9 genotype circulating in Cordoba,
      Argentina, as early as 1980.
AB  - The incidence of human rotavirus G types was determined over a 25-year period
      (1979-2003) by using reverse transcription-PCR (RT-PCR) to examine 519 stool
      specimens found to be positive for rotavirus by enzyme linked immunosorbent assay
      (ELISA) or polyacrylamide gel electrophoresis (PAGE). These stool samples were
      obtained from children under 3 years old who had been treated for acute diarrhea
      at public hospitals in Cordoba, Argentina. The present study describes the
      continued circulation of the common human G types G1 (53.8%), G2 (10.2%), G3
      (4.4%), and G4 (27%), and also the detection of the unusual types G8 (0.5%) and
      G9 (4.2%). Genotype G9 was detected during the 1980-1988 and 1997-2003 periods at
      relatively low rates. Rotavirus G types distribution was independent of age (1-18
      months), gender or out-patient or in-patient status. Unexpectedly, 44.6% of mixed
      infections were detected, involving common and unusual genotypes. Overall, 95.4%
      of the typed strains belonged to the most prevalent human serotypes (G1-G4) but
      the detection of G9 infection throughout this study period highlights the
      importance of this serotype as a human pathogen.

PMID- 16789027
TI  - SCAI membership survey of the 2005 AHA/ACC/SCAI PCI guideline: a summary report
      from the Interventional Committee.

PMID- 16789028
TI  - Pay for quality - what every interventional cardiologist needs to know: part I.

PMID- 16789029
TI  - Efficient diastereoselective intermolecular rhodium-catalyzed C-H amination.

PMID- 16789030
TI  - A three-state model for the photophysics of adenine.
AB  - An ab initio theoretical study at the CASPT2 level is reported on minimum energy
      reaction paths, state minima, transition states, reaction barriers, and conical
      intersections on the potential energy hypersurfaces of two tautomers of adenine:
      9H- and 7H-adenine. The obtained results led to a complete interpretation of the
      photophysics of adenine and derivatives, both under jet-cooled conditions and in
      solution, within a three-state model. The ultrafast subpicosecond fluorescence
      decay measured in adenine is attributed to the low-lying conical intersection
      (gs/pipi* La)(CI), reached from the initially populated 1(pipi* La) state along a
      path which is found to be barrierless only in 9H-adenine, while for the 7H
      tautomer the presence of an intermediate plateau corresponding to an NH2-twisted
      conformation may explain the absence of ultrafast decay in 7-substituted
      compounds. A secondary picosecond decay is assigned to a path involving switches
      towards two other states, 1(pipi* Lb) and 1(npi*), ultimately leading to another
      conical intersection with the ground state, (gs/npi*), with a perpendicular
      disposition of the amino group. The topology of the hypersurfaces and the state
      properties explain the absence of secondary decay in 9-substituted adenines in
      water in terms of the higher position of the 1(npi*) state and also that the
      1(pipi* Lb) state of 7H-adenine is responsible for the observed fluorescence in
      water. A detailed discussion comparing recent experimental and theoretical
      findings is given. As for other nucleobases, the predominant role of a pipi*-type
      state in the ultrafast deactivation of adenine is confirmed.

PMID- 16789031
TI  - Synthesis and stereochemical assignment of DNA spore photoproduct analogues.
AB  - Investigation of the DNA repair process performed by the spore photoproduct (SP)
      lyase repair enzyme is strongly hampered by the lack of defined substrates needed
      for detailed enzymatic studies. The problem is particularly severe because the
      repair enzyme belongs to the class of strongly oxygen-sensitive radical (S)
      adenosylmethionine (SAM) enzymes, which are notoriously difficult to handle. We
      report the synthesis of the spore photoproduct analogues 1 a and 1 b, which have
      open backbones and are diastereoisomers. In order to solve the problem of
      stereochemical assignment, two further derivatives 2 a and 2 b with closed
      backbones were prepared. The key step of the synthesis of 2 a/b is a metathesis
      based macrocyclization that strongly increases the conformational rigidity of the
      synthetic spore photoproduct derivatives. NOESY experiments of the cyclic isomers
      furnished a clear cross-peak pattern that allowed the unequivocal assignment of
      the stereochemistry. The results were transferred to the data for isomers 1 a and
      1 b, which were subsequently used for enzymatic-repair studies. These studies
      were performed with the novel spore photoproduct lyase repair enzyme from
      Geobacillus stearothermophilus. The studies showed an accordance with a recent
      investigation performed by us with the spore photoproduct lyase from Bacillus
      subtilis, in that only the S isomer 1 a is recognized and repaired. The ability
      to prepare a defined functioning substrate now paves the way for detailed
      enzymatic studies of the SP-lyase lesion recognition and repair process.

PMID- 16789032
TI  - Radical-polar crossover domino reactions involving organozinc and mixed
      organocopper/organozinc reagents.
AB  - A domino process involving Michael addition and carbocyclization has been
      developed starting from beta-N-allylamino enoates and various organometallic
      reagents (organozinc halides, diorganozinc reagents, and copper/zinc mixed
      species). In all cases the mechanism of this domino reaction has been evidenced
      to involve a radical-polar crossover mechanism.

PMID- 16789034
TI  - Electric-field modulation of component exchange in constitutional dynamic liquid
      crystals.

PMID- 16789033
TI  - The CFTA method: a reliable procedure for the determination of the absolute
      configuration of chiral primary amines by 1H NMR spectroscopic analysis.

PMID- 16789035
TI  - Cross-hybridization of pyridinedicarboxamide helical strands and their N-oxides.

PMID- 16789036
TI  - Very high rate enhancement of benzyl alcohol oxidation by an artificial enzyme.

PMID- 16789037
TI  - Formation of self-organized dynamic structure patterns of barium carbonate
      crystals in polymer-controlled crystallization.

PMID- 16789038
TI  - A conjugated polycarbazole ring around a porphyrin.

PMID- 16789039
TI  - Twisting nanotubes: from torsion to chirality.

PMID- 16789040
TI  - Electrodeposition of nano- and microcrystalline aluminium in three different air
      and water stable ionic liquids.
AB  - The present work shows, for the first time, a comparative experimental study on
      the electrodeposition of aluminium in three different water and air stable ionic
      liquids, namely 1-butyl-1-methylpyrrolidinium-bis(trifluoromethylsulfonyl)imide
      ([BMP]Tf2N), 1-ethyl-3-methylimidazolium-bis(trifluoromethylsulfonyl)imide
      ([EMIm] Tf2N), and trihexyl-tetradecyl
      phosphoniumbis(trifluoromethylsulfonyl)imide (P(14,6,6,6) Tf2N). The ionic
      liquids [BMP]Tf2N and [EMIm]Tf2N show biphasic behaviour in the AlCl3
      concentration range from 1.6 to 2.5 mol L(-1) and 2.5 to 5 mol L(-1),
      respectively. The biphasic mixtures become monophasic at temperatures >/=80
      degrees C. It was found that nanocrystalline aluminium can be electrodeposited in
      the ionic liquid [BMP]Tf2N saturated with AlCl3. The deposits obtained are
      generally uniform, dense, shining, and adherent with very fine crystallites in
      the nanometer size regime. However, coarse cubic-shaped aluminium particles in
      the micrometer range are obtained in the ionic liquid [EMIm]Tf2N. In this liquid
      the particle size significantly increases as the temperature rises. A very thin,
      mirrorlike aluminium film containing very fine crystallites of about 20 nm is
      obtained in the ionic liquid [trihexyl-tetradecyl-phosphonium]Tf(2)N at room
      temperature. At 150 degrees C, the average grain size is found to be 35 nm.

PMID- 16789041
TI  - Structural studies of 1-butyl-3-methylimidazolium tetrafluoroborate/TX-100/ p
      xylene ionic liquid microemulsions.
AB  - The ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4)
      forms nonaqueous microemulsions with p-xylene, with the aid of the nonionic
      surfactant TX-100. The phase behavior of the ternary system is investigated, and
      three microregions of the microemulsions-ionic liquid-in-oil (IL/O),
      bicontinuous, and oil-in-ionic liquid (O/IL)-are identified by conductivity
      measurements, according to percolation theory. On the basis of a phase diagram, a
      series of IL/O microemulsions are chosen and characterized by dynamic light
      scattering (DLS). The size of aggregates increases on increasing the amount of
      added polar component (bmimBF(4)), which is a similar phenomenon to that observed
      for typical water-in-oil (W/O) microemulsions, suggesting the formation of IL/O
      microemulsions. The microstructural characteristics of the microemulsions are
      investigated by FTIR and 1H NMR spectroscopy. The results indicate that the
      interaction between the electronegative oxygen atoms of the oxyethylene (OE)
      units in TX-100 and the electropositive imidazolium ring may be the driving force
      for the solubilization of bmimBF4 into the core of the TX-100 aggregates. In
      addition, the micropolarity of the microemulsions is investigated by using methyl
      orange (MO) as a UV/Vis spectroscopic probe. A relatively constant polarity of
      the microemulsion droplets is obtained in the IL microemulsion. Finally, a
      plausible structure for the IL/O microemulsion is presented.

PMID- 16789042
TI  - Oriented ensembles in ultrafast electron diffraction.
AB  - Electron scattering expressions are presented which are applicable to very
      general conditions of implementation of anisotropic ultrafast electron
      diffraction (UED) experiments on the femto- and picosecond time scale. "Magic
      angle" methods for extracting from the experimental diffraction patterns both the
      isotropic scalar contribution (population dynamics) and the angular (orientation
      dependent) contribution are described. To achieve this result, the molecular
      scattering intensity is given as an expansion in terms of the moments of the
      transition-dipole distribution created by the linearly polarized excitation laser
      pulse. The isotropic component (n=0 moment) depends only on population and scalar
      internuclear separations, and the higher moments reflect bond angles and evolve
      in time due to rotational motion of the molecules. This clear analytical
      separation facilitates assessment of the role of experimental variables in
      determining the influence of anisotropic orientational distributions of the
      molecular ensembles on the measured diffraction patterns. Practical procedures to
      separate the isotropic and anisotropic components of experimental data are
      evaluated and demonstrated with application to reactions. The influence of
      vectorial properties (bond angles and rotational dynamics) on the anisotropic
      component adds a new dimension to UED, arising through the imposition of spatial
      order on otherwise randomly oriented ensembles.

PMID- 16789043
TI  - On the way to nanometer-sized information of the bacterial surface by tip
      enhanced Raman spectroscopy.

PMID- 16789044
TI  - Adsorption and dynamics of long-range interacting fullerenes in a flexible, two
      dimensional, nanoporous porphyrin network.
AB  - Herein, a detailed investigation of the adsorption and dynamics of C60 and C70
      fullerenes hosted in a self-assembled, two-dimensional, nanoporous porphyrin
      network on a solid Ag surface is presented. Time-resolved scanning tunneling
      microscopy (STM) studies of these supramolecular systems at the molecular scale
      reveal distinct host-guest interactions giving rise to a pronounced dissimilar
      mobility of the two fullerenes within the porphyrin network. Furthermore, long
      range coverage-dependent interactions between the all-carbon guests, which
      clearly affect their mobility and are likely mediated by a complex mechanism
      involving the Ag substrate and the flexible porphyrin host network, are observed.
      At increased fullerene coverage, this unprecedented interplay results in the
      formation of large fullerene chains and islands. By applying a lattice gas model
      with nearest-neighbor interactions and by evaluating the fullerene-pair
      distribution functions, the respective coverage-dependent guest-guest interaction
      energies are estimated.

PMID- 16789045
TI  - Rapid solid-phase peptide synthesis using thermal and controlled microwave
      irradiation.
AB  - A rapid and efficient microwave-assisted solid-phase synthesis method is
      described for the preparation of the nonapeptide WDTVRISFK, using conventional
      Fmoc/Bu(t) orthogonal protection strategy. The synthesis protocol is based on the
      use of cycles of pulsed microwave irradiation with intermittent cooling of the
      reaction during the removal of the Fmoc protecting group and during the coupling.
      The desired nonapeptide was obtained in highest yield and purity by employing
      MicroKan technology. The chemical reactions were carried out in a single-mode
      microwave reactor, equipped with a fiber-optic probe to monitor the reaction
      temperature continuously.

PMID- 16789046
TI  - Reproductive success of bromadiolone-resistant rats in absence of anticoagulant
      pressure.
AB  - Resistance to anticoagulant rodenticides in brown rats (Rattus norvegicus Berk.)
      is associated with pleiotropic effects, notably with an increased dietary vitamin
      K requirement. Owing to this disadvantage, resistance is believed to be selected
      against if anticoagulant selection is absent. In small experimental populations
      of wild brown rats, an investigation was carried out to establish whether
      tolerance to anticoagulant exposure changed over a period of 2 years. In the same
      populations, DNA microsatellite markers were used to infer parentage, and this
      made it possible to estimate reproductive success of sensitive and resistant rats
      and estimate effective population size, Ne. Even though there was evidence for a
      selection against resistant rats with high vitamin K requirement, anticoagulant
      tolerance was not seen to be significantly influenced in the absence of
      bromadiolone selection. As the population size under investigation was small,
      random genetic drift may have played a role in this. In the presence of
      bromadiolone selection, however, the tolerance was significantly increased,
      suggesting that continuous selection will increase the proportion of highly
      resistant rats in the population. It was found that, for both males and females,
      surprisingly few individuals contributed to the next generation with numerous
      offspring, and most breeders contributed with none or a single offspring. The
      expected higher reproductive success and consequent increase in proportional
      numbers of sensitive rats in the absence of anticoagulant selection could not be
      observed. Among the resistant rats, moderately resistant females were found to be
      better breeders than highly resistant breeders, but for resistant males the
      reverse was true. This could be explained by the fact that the increased vitamin
      K requirement results in sex differential selection; in highly resistant males
      the selection presumably takes place at the immature stage, whereas in females
      the vitamin K requirement becomes crucial at the reproductive stage, as vitamin K
      is not only essential for the blood clotting process but also for bone formation.

PMID- 16789047
TI  - Perennial grass rotation: an effective and challenging tactic for nematode
      management with many other positive effects.

PMID- 16789048
TI  - Kinetics, thermodynamics, and the problem of selectivity: the maturation of an
      idea.

PMID- 16789049
TI  - Lipid-anchored oligonucleotides for stable double-helix formation in distinct
      membrane domains.

PMID- 16789050
TI  - Biocatalytic reaction and recycling by using CO2-induced organic-aqueous tunable
      solvents.

PMID- 16789051
TI  - Activation of oxygen on gold/alumina catalysts: in situ high-energy-resolution
      fluorescence and time-resolved X-ray spectroscopy.

PMID- 16789052
TI  - Water-soluble dendrimeric two-photon tracers for in vivo imaging.

PMID- 16789054
TI  - Rhenium trichloride dioxide, ReO2Cl3.

PMID- 16789053
TI  - Short synthesis of (+)-cylindricine C by using a catalytic asymmetric Michael
      reaction with a two-center organocatalyst.

PMID- 16789055
TI  - Gas-phase oxidation of propane and 1-butene with [V3O7]+: experiment and theory
      in concert.

PMID- 16789056
TI  - The coordination chemistry of FeCl3 and FeCl2 to bis[2-(2,3-dihydroxyphenyl)-6
      pyridylmethyl](2-pyridylmethyl)amine: access to a diiron(III) compound with an
      unusual pentagonal-bipyramidal/square-pyramidal environment.
AB  - Coordination of FeCl3 to the title ligand yields a mononuclear iron(III) complex
      1, which was characterized by spectroscopic techniques and X-ray diffraction. The
      ligand is (kappa3-N) tridentate and the metal, which lies in a pseudo-octahedral
      environment, is bound to a phenolate group from the catechol substituent. The
      dichloroiron(II) complex 2 was easily obtained by metalation of the ligand with
      FeCl2 and characterized by various spectroscopic techniques. In their cyclic
      voltammograms both 1 and 2 display the same reversible FeII/FeIII wave at E1/2=10
      mV (vs. SCE). Reduction of compound 1 with Zn/Hg yields 2', which displays
      identical properties to 2. Taken together, these findings indicate that in spite
      of the different oxidation state of the metal in 2, no major
      geometrical/structural change is observed at the metal center with respect to 1.
      The reaction of 2 with dioxygen in the absence of organic substrates proceeds
      extremely rapidly and yields compound 3, which is a diiron(III) derivative whose
      X-ray crystal structure is also reported. The possibility of a radical-based
      mechanism is discussed. Compound 3 displays an unusual geometry: one iron(III)
      center is seven-coordinate, whereas the other lies in a square-pyramidal
      environment. The two iron atoms are bridged by the catecholato substituents. To
      the best of our knowledge, 3 is the first example of a seven-coordinate iron(III)
      derivative with tris(2-pyridylmethyl)amine ligands.

PMID- 16789057
TI  - Expanding the substrate scope of enzymes: combining mutations obtained by
      CASTing.
AB  - In a previous paper, the combinatorial active-site saturation test (CAST) was
      introduced as an effective strategy for the directed evolution of enzymes toward
      broader substrate acceptance. CASTing comprises the systematic design and
      screening of focused libraries around the complete binding pocket, but it is only
      the first step of an evolutionary process because only the initial libraries of
      mutants are considered. In the present study, a simple method is presented for
      further optimization of initial hits by combining the mutational changes obtained
      from two different libraries. Combined lipase mutants were screened for
      hydrolytic activity against six notoriously difficult substrates (bulky
      carboxylic acid esters) and improved mutants showing significantly higher
      activity were identified. The enantioselectivity of the mutants in the hydrolytic
      kinetic resolution of two substrates was also studied, with the best mutant
      substrate combination resulting in a selectivity factor of E=49. Finally, the
      catalytic profile of the evolved mutants in the hydrolysis of simple nonbranched
      carboxylic acid esters, ranging from acetate to palmitate, was studied for
      theoretical reasons.

PMID- 16789058
TI  - Non-biaryl atropisomers in organocatalysis.
AB  - A new class of 6'-hydroxy cinchona alkaloids, with a non-biaryl atropisomeric
      functionalisation at position 5' of the quinoline core can be prepared by an easy
      amination procedure. These are the first derivatives for which the principle of
      atropisomerism is engrafted in the classical core of the cinchona alkaloids. The
      aminated cinchona alkaloids are effective organocatalysts for the Michael
      addition of beta-keto esters to acrolein and methyl vinyl ketone, in up to 93 %
      ee (ee=enantiomeric excess), as well as for the asymmetric Friedel-Crafts
      amination of a variety of 2-naphthols, permitting the preparation of the latter
      in up to 98 % ee. The aminated 8-amino-2-naphthol itself is the first chiral
      organocatalyst based on non-biaryl atropisomerism. The two enantiomers of this
      chiral primary amine can be used for the direct alpha-fluorination of alpha
      branched aldehydes. The fluorinated compounds can thereby be accessed in up to 90
      % ee.

PMID- 16789059
TI  - Nitric oxide-induced fluorescence enhancement by displacement of dansylated
      ligands from cobalt.
AB  - The cobalt complexes [Co(Ds-AMP)(2)] (1) and [Co(Ds-AQ)(2)] (2), where Ds-AMP and
      Ds-AQ are the conjugate bases of dansyl aminomethylpyridine (Ds-HAMP) and dansyl
      aminoquinoline (Ds-HAQ), respectively, were synthesized in two steps as
      fluorescence-based nitric oxide (NO) sensors and characterized by X-ray
      crystallography. The fluorescence of the two complexes was significantly quenched
      in CH(3)CN or CH(3)OH compared to that of the free Ds-HAMP or Ds-HAQ ligands.
      Addition of NO to a CH(3)CN solution of 1 or 2 enhanced the integrated
      fluorescence emission by factors of 2.1(+/-0.3) or 3.6(+/-0.4) within 35 or 20
      min, respectively. Introduction of NO to methanolic solutions of the complexes
      similarly increased the fluorescence by 1.4(+/-0.1) for 1 or 6.5(+/-1.4) for 2
      within 1 h. These studies demonstrate that 1 and 2 can monitor the presence of NO
      with turn-on emission and that their fluorescence responses are more rapid than
      those of previously reported cobalt systems in coordinating solvents such as
      CH(3)CN and CH(3)OH. (1)H NMR and IR spectroscopic data revealed the formation of
      a [Co(NO)(2)](10) cobalt-dinitrosyl adduct, with concomitant dissociation of one
      ligand from the cobalt center, as the metal-containing product of the NO
      reactions, a result indicating NO-induced ligand release to be the cause of the
      fluorescence increase.

PMID- 16789060
TI  - Animal intelligence.

PMID- 16789061
TI  - The management of laryngeal and subglottic stenosis.

PMID- 16789062
TI  - Total hip arthroplasty using the miniature Anatomic Medullary Locking stem.
AB  - We report the outcome of a prospective consecutive series of 52 primary total hip
      arthroplasties using the miniature porous-coated Anatomic Medullary Locking stem
      in patients with small anatomic proportions because of hip dysplasia or juvenile
      chronic arthritis. The mean age of the patients at the time of surgery was 28.7
      years (range 14-56 years). The average body weight and height of the patients
      were 51.8 kg (range 38.5-78.3 kg) and 157.1 cm (range 142.2-183 cm),
      respectively. The stem was cementless in 40 hips and cemented in 12 hips because
      of poor bone stock. A cementless acetabular cup with screw was used in all hips.
      The average followup was 7.1 years (range, 3-15.6 years). The Harris hip scores
      improved from an average of 31.2 points (range, 3.1-68.8 points)preoperatively to
      82.8 points (range, 61.1-96.6 points) at latest followup. Three of 12 (25%)
      cemented and two of 40 (5%) cementless stem were revised. Four of seven 42-44-mm
      cups were revised. The miniature Anatomic Medullary Locking cementless femoral
      stem provides a satisfactory outcome in patients with small anatomic proportions.
      However, wear and osteolysis with the use of a small cementless polyethylene
      liner remain challenges.

PMID- 16789076
TI  - Mystery and myth behind the plesiosaur.

PMID- 16789083
TI  - Virus Particles in Apparently Healthy Peregrinus maidis.
AB  - Virus-like particles were found in apparently healthy Peregrinus maidis (Ashm.)
      in Venezuela. The particles were observed in the salivary gland, intestine,
      mycetome, adipose tissue, ovary, and hemolymph. In the cells, the particles
      occurred in the cytoplasm singly, in groups, free or within vesicles, and in
      hexagonally arranged crystals. In P. maidis from Hawaii such particles were not
      found. However, in these insects, single particles or crystals were observed
      after injecting suspensions of intestines from P. maidis from Venezuela. The
      particles were not observed in insects feeding on plants soiled with excretions
      from particle-containing P. maidis. Particles in organs of insects or in pellets
      of intestines were polygonal and showed a weakly contrasted envelope and a highly
      contrasted core. The particles had a diameter of 54 +/- 9 mmu. They are believed
      to represent a Peregrinus virus causing latent infection.

PMID- 16789084
TI  - Electron microscopy of the formation of wound tumor virus in abdominally
      inoculated insect vectors.
AB  - Fifth-instar nymphs of Agallia constricta leafhoppers were injected abdominally
      with extracts from root tumors confining wound tumor virus (WTV). The insects
      were sacrificed at predetermined intervals, their internal organs dissected,
      fixed, embedded, sectioned, stained, and examined in a Siemens Elmiskop I.
      Sequential stages in virus development were reconstructed from consecutive
      samples of fatbody tissues. Changes resulting from the infection were: (i) a
      viroplasm, i.e., an accumulation of electron-dense aggregates; (ii) the
      appearance at the periphery of the viroplasm of a few fully formed virus
      particles recognized as virions; (iii) the formation of increasing numbers of
      individual virions, not only at the periphery but also in the viroplasm; (iv) the
      engulfing of virions within multimembranous structures; and (v) the formation of
      virus microcrystals either at the sites of former viroplasms, or at some
      distance. These morphological findings indicate that, following abdominal
      inoculation of WTV, the plant-pathogenic virus develops within the cytoplasmic
      matrix proper of insect vector cells. In addition to the fatbody tissues, WTV was
      detected in the epidermis, muscles, and trachea of abdominally inoculated
      insects, demonstrating the systemic invasion of the mechanically infected
      arthropod host. No virus was found in the gut tissues.

PMID- 16789085
TI  - Physicochemical properties of tipula iridescent virus.
AB  - The molecular weight of Tipula iridescent virus, based on sedimentation and
      diffusion coefficients, was 5.51 x 10(8), with hydration of 0.57 g of water per g
      of virus. Deoxyribonucleic acid content, based on total inorganic phosphorus
      liberated, was 19 +/- 0.2%. At 260 mmu, the virus gave an uncorrected absorbance
      of 18.2 cm(2)/mg of virus and a light-scattering corrected absorbance of 9.8
      cm(2)/mg of virus. Amino acid analyses of the virus protein revealed a remarkable
      similarity to Sericesthis iridescent virus. The possibility is discussed that the
      four iridescent insect viruses reported to date bear a strain relationship.

PMID- 16789086
TI  - Application of scanning microscopy in the study of virus transmission of aphids.
AB  - The scanning electron microscope was used in conjunction with the transmission
      electron microscope to study stylet morphology and the role of stylets of the
      green peach aphid in plant virus transmission. The morphology of the stylets
      generally agreed with earlier descriptions of these parts obtained with the
      transmission electron microscopy. A considerable variation seemed to exist in the
      extent and regularity of ridges observed in different individuals, especially
      among apterous adults and nymphs. Surface contamination of stylets as well as of
      the bristle area of the labium could be detected. The possible role of these
      contaminants in plant virus transmission is discussed. Working near the limit of
      resolution of the scanning electron microscope, visualization of two types of
      plant virus particles was attempted. Dipping aphid stylets in suspensions of
      purified virus did not lead to subsequent detection of these particles on the
      stylets with the scanning electron microscope. The scanning microscope is
      evaluated for its possibilities in the study of plant virus transmission by
      insects.

PMID- 16789087
TI  - Double-stranded Ribonucleic Acid from Cytoplasmic Polyhedrosis Virus of the
      Silkworm.
AB  - Ribonucleic acid (RNA) was extracted by phenol treatment from cytoplasmic
      polyhedrosis virus isolated from the midgut of infected silkworms. This RNA
      appears as threads when precipitated in alcohol. Two components having different
      sedimentation constants were observed. The molecular weight of the RNA
      preparation obtained by sedimentation coefficient (weight-averaged) and intrinsic
      viscosity was about 2 x 10(6) to 3 x 10(6). It was one-half to one-third the size
      of the calculated molecular weight for an entire RNA molecule in a virion.
      Electron micrographs of this RNA preparation showed two peaks in the distribution
      of contour length, at 0.4 and 1.3 mum, which would correspond to molecular
      weights of 10(6) and 3 x 10(6), respectively. The extracted RNA seemed to split
      into segments at a preferential breaking point. This RNA was soluble in
      concentrated salt solution, differing from single stranded high-molecular-weight
      RNA. The base composition of this RNA was complementary in the ratios of
      adenosine to uridine and guanosine to cytosine. It contained 43% guanosine plus
      cytosine. Based on its filamentous appearance by electron microscopy, typical
      pattern of optical rotatory dispersion and circular dichroism, sharp transition
      of the optical properties on heating, great hyperchromicity on degradation,
      nonreactivity with formaldehyde, and resistance to ribonucleases, it is concluded
      that this RNA is double-stranded and has regular base pairings of guanosine
      cytosine and adenosine-uridine.

PMID- 16789088
TI  - Electron microscopy of rice transitory yellowing virus.

PMID- 16789089
TI  - Functions of the two particles of tobacco rattle virus.
AB  - Functions of long and short particles of five different tobacco rattle virus
      (TRV) systems were studied by complementation experiments with the corresponding
      long and short species of ribonucleic acid (RNA). The progeny of long RNA species
      alone was proteinless or "free" infectious long RNA, whereas short RNA species
      alone did not replicate by themselves but appeared to be dependent on long RNA
      for replication. When both types of RNA derived from the same isolate were
      inoculated together, particulate virus with long and short particles was produced
      in more than 50% of the resulting primary infections. These virus systems
      obtained by homologous complementation resembled the parent isolates in all their
      characteristics. In addition, heterologous complementation tests were performed
      with long and short RNA, each derived from another isolate. Heterologous
      interaction could be observed in only 2 out of 20 possible combinations. As a
      result, two "mixed" TRV systems with respect to their particle length
      distributions were obtained, since their long and short particles resembled the
      ones from the other isolate. The symptoms produced by these mixed viruses were
      determined by the corresponding long RNA and appeared not to be influenced by the
      heterologous short one. However, the protein coat of both particles of the
      "mixed" viruses was specified by the corresponding noninfectious short RNA.
      Therefore, TRV is a system of at least two functionally defective and mutually
      complementing components which appear to be specialized in early and late
      functions.

PMID- 16789090
TI  - Pathology and Development of the Grasshopper Inclusion Body Virus in Melanoplus
      sanguinipes.
AB  - Grasshoppers, Melanoplus sanguinipes (F.), infected with the grasshopper
      inclusion body virus (GIBV) showed a general torpor, took longer to develop, and
      had abnormally high rates of mortality. Infection was found only in the fat body,
      and developing viruses and inclusion bodies were observed in the nuclei and
      cytoplasm of infected cells. Although the size of the inclusion bodies in cells
      varied at different stages of infection, the inclusion bodies appeared to grow
      during the infection. Electron microscopic investigations of viral replication
      showed that at about 8 days after inoculation presumptive viral particles had
      developed as buds or protrusions from precursor granular masses; thereafter,
      these particles underwent internal differentiation and were incorporated into
      developing inclusion bodies. The GIBV was similar to insect viruses in the genus
      Vagoiavirus Weiser and to pox viruses, particularly vaccinia.

PMID- 16789091
TI  - Apparent in vivo pathway of granulosis virus invasion and infection.
AB  - The invasion and ensuing replication of an insect granulosis virus in
      Trichoplusia ni is described.

PMID- 16789092
TI  - Replication of canine herpesvirus: I. Synthesis of viral deoxyribonucleic Acid.
AB  - This paper reports the results of two series of experiments. The first series
      indicated that deoxyribonucleic acid (DNA) extracted from partially purified
      canine herpesvirus virions is characterized by a high guanine plus cytosine molar
      base ratio (65 to 67 mole%), similar to the DNA of herpes simplex virus. In the
      second series of experiments it was estimated, on the basis of uptake of
      tritiated thymidine, that in dog kidney cells canine herpesvirus-DNA synthesis
      starts at 4 hr and continues until 16 hr after infection. Treatment of infected
      cells with puromycin during the first 4 hr of infection blocks the onset of viral
      DNA synthesis, whereas, after this time the uptake of thymidine is unaffected.

PMID- 16789093
TI  - Poliovirus-induced Cellular Injury.
AB  - Protein leakage was used as a quantitative measure of poliovirus-induced cellular
      injury under suspended cell culture conditions. The requirements for protein
      leakage were studied in detail and it was established that events early in the
      infectious cycle which depend upon viral protein synthesis were responsible for
      cell damage. Extralysosomal beta-glucuronidase appeared in infected cells before
      the onset of protein leakage and release of newly synthesized virus.
      Hydrocortisone treatment of infected cells resulted in only a slight delay in the
      release of beta-glucuronidase from lysosomes and protein and virus from cells.
      These results suggest that events associated with poliovirus synthesis trigger
      the release of lysosomal hydrolases which in turn injure the plasma membrane,
      allowing cytoplasmic proteins and virus to leak out of the cell.

PMID- 16789094
TI  - Delayed lysis with a mutant of salmonella bacteriophage p22.
AB  - A mutant of bacteriophage P22 (Lys(-)) was isolated which shows a plaque
      morphology on mixed plates comparable to the r(+) plaques of the T-even phages.
      When Lys(-) and normal Lys(+) plaques are juxtaposed on a petri dish, the Lys(+)
      plaque exhibits a flat side adjacent to the Lys(-) plaque. The mutant is
      identical to P22 under an electron microscope, is inactivated at the same rate by
      antiserum and heat, and has the same kinetics of attachment. It does not plate on
      Salmonella lysogenic for phage P22 nor on strain St/22. In liquid culture, the
      lysis of mutant infections in M9CAA medium is delayed between 20 and 40 min.
      Cells mixedly infected in M9CAA with Lys(-) and Lys(+) phage lyse later than
      Lys(+)-infected cells and even later than Lys(-)-infected cells. In
      unsupplemented M9 medium, however, mixedly infected cells again lyse later than
      Lys(+)-infected cells, but Lys(-)-infected cells require more than 3 hr to lyse.
      In supplemented and unsupplemented M9 media, intracellular phage development and
      endolysin synthesis proceed in Lys(-) infections at least as rapidly as in Lys(+)
      infected cells. In diluted infections, the latent and eclipse periods of Lys(-)
      and Lys(+) infections are indistinguishable. The possible mechanisms involved in
      the control and timing of lysis are discussed.

PMID- 16789095
TI  - Delayed lysis with salmonella bacteriophage p22: induction of lysis by addition
      of cysteine or histidine to the growth medium.
AB  - A mutant (Lys(-)) of Salmonella bacteriophage P22 showed a delay in lysis of more
      than 3 hr in infections in unsupplemented M9 medium. The infected cells were
      induced to lyse during that interval by addition of histidine or sulfhydryl
      compounds cysteine, mercaptoethanol, glutathione, or ergothioneine. Urocanic
      acid, the first intermediate in the catabolic histidine pathway, did not induce
      lysis, nor did histamine, imidazolelactate, or carnosine. None of the other amino
      acids common to protein had any inductive effect. Both the d and l forms of
      histidine were effective in inducing lysis, suggesting that the incorporation of
      the histidine into protein is not involved. Chloramphenicol inhibited lysis when
      added at 60 min with or without histidine, but did not inhibit the induction of
      lysis when added with cysteine. Bacterial cells infected with Lys(+) phage were
      induced to lyse prematurely when cysteine was added at 30 min but not at 20 min
      of infection. Iodoacetate inhibited lysis of Lys(+)-infected cells when added at
      20 min but not at 30 min.

PMID- 16789096
TI  - Some properties of influenza virus nucleocapsids.
AB  - Nucleocapsids released from influenza virions by sodium deoxycholate sedimented
      heterogeneously in sucrose gradients. Highly infectious virus (complete)
      preparations yielded nucleocapsids with peak distributions at 64 and 56S; von
      Magnus type virus (incomplete) lacked 64S nucleocapsids. Treatment of influenza
      virus nucleocapsids with pancreatic ribonuclease rendered the associated viral
      ribonucleic acid (RNA) molecules acid-soluble, indicating that capsid proteins do
      not completely surround the viral RNA's. However, the capsid proteins remained
      associated after enzymatic hydrolysis of the RNA, as judged by persistently high
      sedimentation rates. Sedimentation rates of viral nucleocapsids reflected the
      sedimentation rates of the associated RNA's: 64S nucleocapsids contained 18S RNA,
      whereas 56S nucleocapsids contained 15S RNA, although in both cases RNA's
      sedimenting at 4 to 13S were also recovered. Furthermore, just as incomplete
      virions lacked 64S nucleocapsids, they also lacked 18S RNA. These findings
      support the hypothesis that the influenza virus genome is divided among several
      distinct pieces of RNA.

PMID- 16789097
TI  - Rescue of Simian Virus 40 from Cell Lines Transformed at High and at Low Input
      Multiplicities by Unirradiated or Ultraviolet-irradiated Virus.
AB  - The relation between simian virus 40 (SV40) input multiplicity during
      transformation of primary mouse kidney cultures and the subsequent rescue of SV40
      from clonal lines of transformed cells has been studied. Primary mouse kidney
      cultures were transformed with unirradiated SV40 at input multiplicities varying
      from 0.06 to 200 plaque-forming units (PFU) /cell or with SV40 irradiated with
      ultraviolet (UV) light to a survival of 0.04 to 0.01. All of the transformed
      lines contained the intranuclear SV40 T antigen, but cell-free extracts prepared
      from the transformed cell lines failed to yield infectious virus when assayed on
      monkey kidney cell (CV-1) monolayers. After fusion with susceptible CV-1 cells
      induced by UV-inactivated Sendai, all of the lines transformed by unirradiated
      virus yielded infectious SV40. The frequency of induction and the incidence of
      successful trials did not depend on the multiplicity of infection. "Good"
      yielders were obtained from mouse kidney cells transformed at the low input
      multiplicity of 0.06 PFU /cell. In contrast, only 4 of 12 clonal lines
      transformed at moderately low input multiplicity, and none of the lines
      transformed at very low input multiplicity with UV-irradiated virus yielded
      infectious SV40. The four positive lines have been classified as "poor" or "rare"
      yielders.

PMID- 16789098
TI  - Properties of adenovirus messenger ribonucleic Acid synthesized in vitro.
AB  - Adenovirus deoxyribonucleic acid (DNA) was used as template for the in vitro
      synthesis of viral-specific ribonucleic acid (RNA). When the kinetics of the
      reaction were compared by using native and heat-denatured DNA templates, the
      latter synthesized RNA at a slower rate. The fate of the DNA after acting as
      template and physical characteritstics of the RNA product were studied. The DNA
      template, according to its sedimentation rate, was not significantly degraded by
      the Micrococcus lysodeicticus RNA polymerase. The products of the RNA polymerase
      reaction had the following properties. (i) Hybridization experiments revealed a
      high degree of complementarity (50 to 70%) for its homologous DNA. (ii) A very
      low complementarity (6 to 7%) was found for its heterologous DNA. (iii) The
      sedimentation rate of the synthetic RNA in a sucrose gradient was 5 to 10S when
      native DNA was used as the template. When heat-denatured DNA was used, the
      resulting RNA product, free of the template, sedimented at a rate of 3 to 16S. A
      rapidly sedimenting (>30S) DNA-RNA complex resulted when denatured DNA was the
      template. The DNA moiety of the complex was sensitive to 125 mug of
      deoxyribonuclease per ml. The RNA of the complex, however, was fully refractory
      to 50 mug of ribonuclease per ml. When the adenovirus DNA was sonically treated
      and then used as template, the RNA product sedimented at 3 to 9S. The heat
      denatured sonically treated DNA template yielded a DNA-RNA complex that also
      sedimented at an unusually fast rate (>18S).

PMID- 16789099
TI  - Dependence of Vegetative Recombination Among Haemophilus influenzae Bacteriophage
      on the Host Cell.
AB  - Vegetative recombination of temperature-sensitive mutants of Haemophilus
      influenzae phage HP1 cl was measured in wild-type H. influenzae strain Rd and in
      strain DB117, an ultraviolet-sensitive, transformation-defective mutant of the Rd
      strain. Recombinants are formed with low frequency in wild-type cells, but no
      recombination was detectable in DB117. It is concluded that these phage make use
      of the host cell enzymes for vegetative recombination. Lysogenization readily
      takes place in both strains.

PMID- 16789100
TI  - Cells persistently infected with newcastle disease virus: I. Properties of
      mutants isolated from persistently infected L cells.
AB  - The strain of Newcastle disease virus (NDV(pi)) present in persistently infected
      L cells differed markedly from the Herts strain (NDV(0)) used to initiate the
      infection. NDV(pi) produced small plaques (less than 1 mm) in chick embryo cell
      cultures, whereas the wild type (NDV(0)) produced large plaques (2 to 3 mm). The
      two viruses differed in a number of additional properties. Whereas 80% of
      adsorbed NDV(0) eluted from chicken red blood cells at 37 C, only about 20% of
      NDV(pi) was recovered under similar conditions. There was no significant
      difference in the neuraminidase content of the two viruses. The infectivity of
      NDV(0) was stable for 1 hr at 48 C, whereas 99.9% of the infectivity of NDV(pi)
      was destroyed. The two viruses also differed in lethality for chick embryos;
      NDV(pi) had significantly reduced lethality for 9-day-old chick embryos when
      compared to NDV(0). In contrast to NDV(0), which produced an abortive infection
      in L cells, NDV(pi) not only replicated effectively and destroyed these cells,
      but also induced significantly higher quantities of interferon than did NDV(0).
      These data furnished additional evidence for the lack of relationship of
      interferon production to abortive infection of L cells with NDV(0). In contrast,
      interferon was found to play a significant role in the maintenance of persistent
      infection.

PMID- 16789101
TI  - Phenotypic suppression by streptomycin of amber mutants in the ribonucleic Acid
      bacteriophage coat protein cistron.
AB  - After mutagenesis with nitrosoguanidine or ultraviolet light, 298 streptomycin
      high-resistant and 98 streptomycin high-dependent mutants were isolated from HfrC
      Su(-). They were tested for their ability to phenotypically suppress five
      different amber ribonucleic acid (RNA) bacteriophage mutants in the presence of
      streptomycin. The phage mutants are all in the coat protein, which is 129 amino
      acids long; the uracil-adenine-guanine codons were at the following positions:
      sus3 and amB2, 6; amB11, 50; amB21, 54; sus11, 70. Only sus3 and amB2 could be
      phenotypically suppressed by streptomycin; this was clearly demonstrated in nine
      mutant strains, seven str-HR and two str-HD. The suppression was always dependent
      upon added streptomycin and was dose-dependent in all cases. None of the mutants
      showed measurable suppression in absence of the drug. Among revertants to
      streptomycin independence from streptomycin-dependent strains that could show
      phenotypic suppression, most of those that were still resistant to streptomycin
      (10 mug or more) retained the capacity to show phenotypic suppression; whereas
      among those revertants sensitive to 10 mug of streptomycin or less, none retained
      the capacity. Eight different amber polar mutants (strong and weak) in gene 34 of
      phage T4 were also tested for pleiotypic suppression by streptomycin in all the
      streptomycin-resistant and -dependent strains isolated. No suppression was found
      in any of the 396 strains tested.

PMID- 16789102
TI  - Fate of adenovirus type 12 genomes in nonpermissive cells.
AB  - The fate of (3)H-thymidine-labeled adenovirus type 12 deoxyribonucleic acid (DNA)
      was studied in Nil-2 cells of Syrian hamster origin. It was found that a
      substantial fraction of (3)H-adenovirus type 12 DNA became degraded within 24 hr
      after infection and was released into the culture fluid. After infection of 5
      bromodeoxyuridine (BUdR)-prelabeled cells with (3)H-adenovirus type 12, viral DNA
      became readily separable from cellular DNA by equilibrium centrifugation in CsCl.
      Part of the viral radioactivity was found to shift gradually to the position of
      cellular DNA as time progressed after infection. When exponentially growing cells
      were exposed simultaneously to BUdR, 5-fluorodeoxyuridine, and (3)H-adenovirus
      type 12, up to 50% of the viral radioactivity shifted within 24 hr from the
      density of viral DNA to that of cellular DNA after equilibrium centrifugation in
      CsCl. Upon denaturation of the cellular DNA, the isotope was preferentially found
      to be associated with the "heavy" strand which was synthesized after infection.
      Upon hybridization of the "heavy" and the "light" strands with sonically treated,
      denatured (3)H-adenovirus type 12 DNA, small and nearly equal amounts of counts
      hybridized with both strands. The number of counts annealed was in a range
      similar to that of those annealed with the same amount of DNA derived from
      adenovirus type 12-transformed hamster cells. These results demonstrate that (i)
      a substantial proportion of the adsorbed virus becomes degraded within 24 hr;
      (ii) part of the degradation products is reutilized for cellular DNA synthesis;
      (iii) only a small fraction, mainly fragments, of viral DNA becomes integrated
      into both the newly synthesized and the parental strands of cellular DNA.

PMID- 16789103
TI  - Characterization of Temperate Bacillus Bacteriophage phi105.
AB  - Temperate Bacillus phage phi105 is serologically unrelated to previously
      described virulent Bacillus phages. Phage phi105 is incapable of generalized
      transduction. Prophage phi105 is inducible with mitomycin C. Phage phi105
      contains double-stranded deoxyribonucleic acid (DNA) with a molecular weight of
      about 25 x 10(7) as determined by band sedimentation and electron microscopy. The
      per cent guanine plus cytosine of phi105 DNA is 43.5 as determined by buoyant
      density in CsCl and by thermal denaturation. Phage phi105 DNA may contain
      complementary single-stranded ends.

PMID- 16789104
TI  - Morphogenesis of aura virus.
AB  - Aura virus, a member of the Western equine-encephalitis-Whataroa subgroup of
      group A arboviruses, was studied by electron microscopy in suckling mouse brain
      and chick embryo cultured cells. Virus precursors, budding particles, and
      complete virus particles were first detected 10 hr after infection in chick
      embryo cells and 24 hr after inoculation in mouse brain. Virus precursors were
      generally seen aligned along cytomembranes, and were less frequently seen closely
      associated with viroplasm-like foci, tubular aggregates, or scattered in the
      cytoplasmic matrix without an apparent connection to any other structure. The
      assembly of mature virus was observed to take place by a budding process of the
      virus precursor from the plasma membrane into the extracellular space, and from
      the cytoplasmic membranes into the lumina of vacuoles and cisternae. It was
      demonstrated that the endoplasmic reticulum participates in the assembly of
      intracellular virions. Indirect evidence was found to indicate that the Golgi
      complex may also form mature virus. Aura virions had a size, shape, and structure
      similar to those of the previously described group A arboviruses.

PMID- 16789105
TI  - Precursor Products Found in Formaldehyde-fixed Lysates of BHK-21 Cells Infected
      with Pseudorabies Virus.
AB  - Lysates of BHK-21 cells, infected with pseudorabies and labeled with (3)H
      thymidine, were treated with formaldehyde and centrifuged in preformed CsCl
      gradients. Five peaks, designated bands A to E, were detected and shown to
      contain the following virus-specific products: band A, aggregates of virions;
      band B, virions; band C, empty capsids and nucleocapsids; bands D and E, small
      nucleoid-like particles. All five bands contained viral deoxyribonucleic acid and
      virous-specific antigens. Deoxyribonuclease treatment of the lysates before
      centrifugation resulted in the complete loss of (3)H-thymidine-labeled material
      from bands D and E; bands B and C were unaffected. Pulse-chase studies showed
      that (3)H-thymidine can be rapidly chased into the virus-specific products
      sedimenting in bands D and E. Further chase resulted in the gradual loss of label
      from bands D and E with a concomitant increase in the amount of label in bands A,
      B, and C. These results indicate that the virus-specific products in bands D and
      E are precursors of pseudorabies virions and may represent the nucleoid of the
      virion.

PMID- 16789106
TI  - Inhibition of arbovirus assembly by cycloheximide.
AB  - Addition of cycloheximide (100 mug/ml) to cultures of chick cells infected with
      Semliki Forest virus (SFV) halted subsequent increase in virus titers. When added
      after 4 hr of infection, the drug had no effect on the rate of viral ribonucleic
      acid (RNA) synthesis, although marked inhibition of protein synthesis was seen.
      All of the previously identified forms of SFV RNA were seen in the drug-treated
      cells at higher concentrations than were present in untreated controls. The
      latter observation appeared to result from a failure to form viral "cores" or
      nucleocapsids in the cycloheximide-treated cells, resulting in sequestration of
      viral RNA intracellularly. The failure to form new virus cores was correlated
      with the failure of type II cytopathic vacuoles to appear in thin sections. Virus
      budding from the cell surface and the formation of type I cytopathic vacuoles
      persisted in cycloheximide-treated cells. The cellular pool of the major protein
      present in the virus core appeared to be small. None of this protein was found in
      a free pool in cytoplasm. The results indicated that, in the presence of
      cycloheximide, virus assembly was impaired because of the small size of the
      cellular pool of the major protein required for virus core formation.

PMID- 16789107
TI  - Characterization of Xanthomonas phaseoli Bacteriophages.
AB  - Ten bacteriophages for Xanthomonas phaseoli were characterized. On the basis of
      adsorption rates, latent period and burst size, plaque morphology, host range,
      efficiency of plating, ultrastructure, sensitivity to osmotic shock, streptomycin
      sensitivity, temperature effects on plating efficiency, and serology, the phages
      were separated into at least three groups. Some of the phages were infectious for
      Pseudomonas phaseolicola (four strains) and P. syringae (one strain) in a narrow
      temperature range. The taxonomic and ecological significance of this finding is
      discussed.

PMID- 16789108
TI  - Lysogenic Conversion in Bacillus amyloliquefaciens H Affecting Viral Adsorption.
AB  - Lysogenization of Bacillus amyloliquefaciens H with bacteriophage PK renders the
      bacteria resistant to superinfection with bacteriophage of PK type.

PMID- 16789109
TI  - Deoxyribonucleic Acid synthesis in insect larvae after inoculation with
      nucleopolyhedrosis virus.
AB  - Studies of deoxyribonucleic acid synthesis following inoculation with nucleo
      polyhedrosis show a large burst of viral deoxyribonucleic acid synthesis late in
      the infection period.

PMID- 16789110
TI  - Persistent infection of a rat nephroma cell line with kilham rat virus.
AB  - A rat nephroma cell line was found to be a carrier culture of the Kilham rat
      virus. Infectious virus was demonstrable only by passage of culture materials
      into other host systems.

PMID- 16789111
TI  - Inactivation of rubella virus by gamma radiation.
AB  - The Gilchrist and M-33 strains of rubella virus exposed in the frozen state to
      (137)Ce or (60)Co were inactivated exponentially according to "one hit" kinetics.
      There was no difference in the radiosensitivity of the two strains. Experimental
      D(37) values for both strains ranged from 1.9 x 10(5) to 2.9 x 10(5) rads, and
      computed radiosensitive molecular weights ranged from 2.6 x 10(6) to 4.0 x 10(6)
      daltons.

PMID- 16789112
TI  - Nonsense Mutants in the rII A Cistron of Bacteriophage T4.
AB  - After in vitro treatment of bacteriophage T4 with hydroxylamine (HA), 54 nonsense
      mutants in the rII A cistron were isolated. These mutants were characterized by
      growth on suppressor strains of Escherichia coli, and the mutational sites were
      mapped in the rII A cistron. Twenty-five (9 sites) were amber (UAG), 20 (6 sites)
      were opal (UGA), and 9 (6 sites) were ochre (UAA). Mapping experiments further
      indicated that there were three closely linked pairs of amber and opal mutations,
      conceivably involving mutations occurring in adjacent nucleotides. Based on the
      specificity of HA mutagenesis (GC --> AT), the amino acid codons in which the
      mutations occurred have been inferred. It is suggested that the three amber-opal
      pairs arose in tryptophan codons (UGG) and the six ochre mutants arose in
      glutamine codons (CAA). The six unpaired ambers and the three unpaired opals have
      been tentatively assigned to glutamine codons (CAG) and arginine codons (CGA),
      respectively, in the wild-type phage.

PMID- 16789113
TI  - Ribonucleic Acid and protein synthesis in chick embryo cells infected with fowl
      plague virus.
AB  - Fowl plague virus comprised four major protein components and several minor ones,
      two strains of the virus giving similar results. One of the components was
      identified as the nucleocapsid protein. Synthesis of the virion proteins could
      readily be detected in infected cells 3 hr after infection. The two subcellular
      fractions associated with viral ribonucleic acid (RNA) polymerase activity
      (nuclei and ribosomal pellet) were associated with the protein of the
      nucleocapsid and a second virion protein of unidentified function. Measurement of
      viral RNA and protein synthesis in cells infected with preparations of
      ultraviolet irradiated virus showed that the capacity to synthesise the RNA and
      protein species of highest molecular weight was lost most quickly, suggesting
      that the pieces of viral RNA function independently.

PMID- 16789114
TI  - Restoration by Chloramphenicol of Bacteriophage Production in Escherichia coli B
      Infected with a Ligase-Deficient Amber Mutant.
AB  - The addition of chloramphenicol (CM) 5 min after infection of the nonpermissive
      host Escherichia coli B with the ligase-negative T4 amber, T4 AmH39X, allowed
      replication of parental deoxyribonucleic acid (DNA) and the production of high
      molecular-weight progeny DNA, composed mostly of subunits with a D(2)/D(1) of
      0.6. When CM was removed after the accumulation of a large pool of this DNA, most
      of the infected bacteria were able to produce viable progeny phage, with an
      average yield of approximately 15 bacteriophage per bacterium. This phenomenon is
      called CM rescue of the ligase-negative T4 Am. CsCl and sucrose gradient analyses
      showed both the resulting phage and DNA extracted from them to be similar to the
      phage and DNA produced on the permissive host. The total transfer of the parental
      label to progeny phages was as high as 20%. In contrast, in bacteria not treated
      with CM or in bacteria to which CM was added after phage-coded nucleases had
      already been synthesized, both parental and progeny (newly synthesized) DNA was
      composed of very short fragments. Phage which are produced under conditions other
      than those of CM rescue are dead, light in CsCl, and contain only very short
      fragments of DNA. Parent-to-progeny transfer in this case is below 1%. When light
      radio-active parental DNA was used to infect heavy bacteria, DNA replicating in
      the CM rescue conditions assumed only a hybrid density. After removal of CM and
      maturation, the parental DNA was incorporated into progeny molecules in fragments
      constituting approximately 7 to 10% of its mass. This pattern of distribution is
      essentially what is observed in similar experiments in the permissive host. The
      role of ligase as an enzyme which compensates for the lethal action of phage
      coded nuclease and which is stringently required for the repair of single
      stranded nicks is emphasized. The possibility of specific sites for a unique
      cutting enzyme is discussed in connection with the hypothesis of a circularly
      permuted assembly of sets.

PMID- 16789115
TI  - Inheritance of Susceptibility to Friend Mouse Leukemia Virus: VI. Reciprocal
      Alteration of Innate Resistance or Susceptibility by Bone Marrow Transplantation
      Between Congenic Strains.
AB  - Two newly established mouse strains which are congenic with standard inbred
      strains were used for the study of the locus Fv which controls the susceptibility
      to Friend leukemia virus in mice. A strain in each congenic pair shares the major
      histocompatibility gene with the corresponding partner strain but differs from
      the latter in the Fv locus. Mice with Fv(r)/Fv(r) genotype (DDD-Fv(r), C57BL/6)
      do not develop marked spleen enlargement upon virus challenge, whereas spleens of
      mice with Fv(s)/Fv(s) genotype (DDD, C57BL/6-Fv(s)) become large even with a
      virus inoculum 1/10(3) to 1/10(5) times that used for the resistant strains. Mice
      of each strain were heavily irradiated, inoculated with bone marrow cells taken
      from either syngenic or corresponding congenic mice, and challenged later with
      the leukemia virus. When Fv(s)/Fv(s) mice had been restored with bone marrow
      cells taken from Fv(r)/Fv(r) mice, the spleens remained small after the virus
      inoculation. In contrast, Fv(r)/Fv(r) mice receiving Fv(s)/Fv(s) cells responded
      to the virus with marked spleen enlargement. In the enlarged spleens of the
      C57BL/6 mice which do not otherwise allow the virus multiplication, a
      considerable amount of infectious virus was found. The altered response seems to
      be due to repopulation of destroyed tissues by the transplanted bone marrow
      cells. It is concluded that the locus Fv is expressed on hemopoietic cells, and
      cells derived from bone marrow play a predominant role in the development of
      splenomegaly by Friend leukemia virus.

PMID- 16789116
TI  - Defective Bacteriophage PBSH in Bacillus subtilis: III. Properties of Adenine-16
      Marker in Purified Bacteriophage Deoxyribonucleic Acid.
AB  - The adenine-16 (ade-16) marker (the marker nearest the chromosomal origin of
      Bacillus subtilis) in purified PBSH deoxyribonucleic acid (DNA) renatured more
      rapidly and to a greater extent than any other marker in the phage DNA, and more
      rapidly and to a greater extent than all markers, including ade-16, in bacterial
      DNA. The renaturation of the phage DNA ade-16 marker followed a first-order
      reaction, whereas renaturation of bacterial markers was initially a second-order
      reaction. No cross-linkages were detected in DNA molecules containing the ade-16
      marker. Buoyant density measurements and inactivation by heat and micrococcal
      deoxyribonuclease of the ade-16 marker did not reveal large segments of clusters
      of the individual bases in these molecules. Alternative mechanisms for the unique
      renaturation behavior of the ade-16 marker are discussed.

PMID- 16789117
TI  - Comparison of the ribonucleic Acid subunits of reovirus, cytoplasmic polyhedrosis
      virus, and wound tumor virus.
AB  - Double-stranded ribonucleic acid (RNA) from intact cytoplasmic polynedrosis virus
      (CPV) and wound tumor virus (WTV) was analyzed by polyacrylamide gel
      electrophoresis. Using RNA from type 3 reovirus as a standard, it was calculated
      that CPV-RNA consisted of 9 subunits corresponding to a molecular weight of 12.7
      x 10(6) and WTV-RNA consisted of 12 subunits corresponding to a molecular weight
      of 15.5 x 10(6).

PMID- 16789118
TI  - Characterization of a Ribonucleic Acid Polymerase Activity Associated with
      Purified Cytoplasmic Polyhedrosis Virus of the Silkworm Bombyx mori.
AB  - Purified cytoplasmic-polyhedrosis virus has been found to have associated with it
      a polymerase activity capable of catalyzing the synthesis of virus-specific,
      single-stranded ribonucleic acid (RNA) from the double-stranded RNA genome.

PMID- 16789119
TI  - Characterization of deoxyribonucleases induced by poxviruses.
AB  - Increases in deoxyribonuclease activity assayed at alkaline pH can be observed in
      poxvirus-infected cells when native or denatured deoxyribonucleic acid (DNA) is
      used as substrate. The deoxyribonuclease assayable with native DNA as substrate,
      induced in HeLa cells by cowpoxvirus or vaccinia virus WR, can be separated from
      the corresponding enzyme present in normal cells by chromatography on
      diethylaminoethyl cellulose. In addition, the two enzymes induced in the virus
      infected cells differ from each other in their chromatographic properties. The
      two induced enzymes have been further characterized with respect to properties of
      enzymatic reaction.

PMID- 16789120
TI  - Effect of cell physiological state on infection by rat virus.
AB  - Infection by rat virus has been studied in cultures of rat embryo cells to
      evaluate the Margolis-Kilham hypothesis that the virus preferentially infects
      tissues with actively dividing cells. An enhancement of infection was seen in
      cultures infected 10 hr after fresh medium was added as compared to infection of
      stationary cultures (infected before addition of fresh medium). Since addition of
      fresh medium stimulates deoxyribonucleic acid (DNA) synthesis, the number of
      cells per culture synthesizing DNA at the time of infection was compared with the
      proportion of cells which synthesized viral protein. Cells were infected before
      the medium change and 10 or 24 hr after the medium change and were pulse-labeled
      with (3)H-thymidine at the time virus was added. The cells were allowed to
      initiate viral protein synthesis before they were fixed and stained with
      fluorescein-conjugated anti-rat virus serum. Fluorescence microscopy permitted
      both labels to be counted simultaneouly and showed that the greatest proportion
      of cells synthesizing viral protein were those which had incorporated (3)H
      thymidine at the time of infection.

PMID- 16789121
TI  - Similarities and Differences in the Development of Laboratory Strains and Freshly
      Isolated Strains of Herpes Simplex Virus in HEp-2 Cells: Electron Microscopy.
AB  - HEp-2 cells infected with two laboratory strains (mP and MP) and two freshly
      isolated strains (F and G) of herpes simplex virus were fixed at intervals
      between 4 and 50 hr postinfection and sectioned, and were then examined with the
      electron microscope. These studies revealed the following. (i) All four strains
      caused identical segregation of nucleoli and aggregation of host chromosomes at
      the nuclear membrane. (ii) The development of MP virus could not be
      differentiated from that of its parent mP strain. (iii) There were quantitative
      differences between laboratory (mP) and freshly isolated (F) type 1 strains.
      Thus, cells infected with F contained numerous nuclear crystals of nucleocapsids
      and relatively few cytoplasmic structures containing enveloped nucleocapsids.
      Conversely, cells infected with mP or with MP virus contained numerous
      cytoplasmic structures with enveloped nucleocapsids and relatively few nuclear
      crystals of nucleocapsids. (iv) There were qualitative differences between type 2
      strain (G) isolated from genital lesions and type 1 strains. Thus, cells infected
      with the G strain contain numerous filaments in nuclei and unenveloped and
      partially enveloped nucleocapsids in the cytoplasm. Of particular interest is the
      finding that cytoplasmic membranes in apposition to nucleocapsids were thickened
      and bent as if they were enveloping the particle. The significance of the
      qualitative differences in the development of the four strains is discussed.

PMID- 16789122
TI  - Role of lysine in the replication of reovirus: I. Synthesis of complete and empty
      virions.
AB  - Lysine is essential for the replication of infectious reovirus. Omission of
      lysine from the extracellular medium not only permitted the continued synthesis
      of structural viral proteins and viral double-stranded ribonucleic acid (RNA),
      but also caused an enhanced formation of viral structures which were separable by
      isopycnic sedimentation of CsCl into a top band consisting of empty particles
      with a buoyant density of 1.29 g/cm(3) and essentially free of viral RNA, and two
      lower bands which were difficult to resolve and had an average buoyant density of
      1.37 g/cm(3). The lower bands contained most of the viral nucleic acid. The above
      effects were reversed when lysine was restored early after infection. In
      contrast, a single band with a buoyant density of 1.38 g/cm(3) was obtained from
      lysine-plus infected cells.

PMID- 16789123
TI  - Pasteurella Bacteriophage Sex Specific in Escherichia coli.
AB  - Phage H, thought to be specific for Pasteurella pestis, was shown to plate
      efficiently on F(-) strains of Escherichia coli but not on F(+), F', or Hfr
      strains. The phage was adsorbed rapidly to F(-) strains but was not adsorbed to
      strains carrying F. Comparison with seven other reported female-specific phages
      showed that, although phage H was similar to the other phages in some
      characteristics, the exceptionally low efficiency of plating (<10(-9)) on F
      containing cells makes phage H a particularly useful female-specific phage.

PMID- 16789124
TI  - Synthesis of viral-specific ribonucleic Acid in rubella virus-infected cells.
AB  - Monolayers of BHK-21/W1-2 cells were pulsed with (3)H-uridine at different times
      after infection with rubella virus, and viral-specific cytoplasmic ribonucleic
      acid species were demonstrated.

PMID- 16789125
TI  - Morphology of echovirus 22.
AB  - Purified preparations of echovirus 22 were examined in the electron microscope.
      The virus was found to possess 32 capsomers arranged at the vertices of either a
      pentakis dodecahedron or a rhombic triacontahedron. The size of the virions
      ranges from 22 x 10(-3) to 32 x 10(-3) mum with a mean of 27 x 10(-3) mum and a
      mode of 28 x 10(-3) mum.

PMID- 16789126
TI  - Density differences between hybrid and nonhybrid particles in two adenovirus
      simian virus 40 hybrid populations.
AB  - The adenovirus 7-simian virus 40 hybrid virus population E46(+) was subjected to
      fixed-angle equilibrium density gradient centrifugation in CsCl. A difference in
      buoyant density between the hybrid virion and its nonhybrid adenovirus 7
      counterpart was noted, the hybrid virion possessing the lower buoyant density.
      This difference in buoyant density appeared to be accentuated in a population of
      adenovirus 2(+t7), a derivative of E46(+) in which the adenovirus 7-simian virus
      40 genome had been transferred to an adenovirus 2 capsid.

PMID- 16789127
TI  - Molecular Recombination in T4 Bacteriophage Deoxyribonucleic Acid: III. Formation
      of Long Single Strands During Recombination.
AB  - Evidence was presented to support the hypothesis that long single strands
      appearing at late times (15 min after infection) are produced as a result of
      recombination and not as a continuous elongation during the replication process.
      The production of long strands does not depend on the multiplicity of infection,
      and the first long strands appear at the time when 20 to 50 phage equivalent
      units of deoxyribonucleic (DNA) are synthesized, and not earlier. The addition of
      chloramphenicol at 5 min, which prevents molecular recombination but allows
      replication of DNA, prevents the formation of long, single strands.
      Chloramphenicol added between 8 and 10 min after infection, a time at which
      molecular recombination is fully expressed and covalent repair of recombinant
      molecules is allowed, does not prevent formation of long single strands. Cutting
      of single-strand DNA with a limited amount of endonuclease I allows confirmation
      that the fast-sedimenting characteristic of intracellular denatured DNA is caused
      primarily by the length of the strands, and not by the formation of aggregates.
      The computer simulation of two recombination models indicates the feasibility of
      random breakage and rejoining of molecules in generating long concatenates.

PMID- 16789128
TI  - Complementary Strands of Bacteriophage phi29 Deoxyribonucleic Acid: Preparative
      Separation and Transcription Studies.
AB  - Bacillus subtilis phage phi29 has a nonpermuted, duplex deoxyribonucleic acid
      (DNA) with cohesive ends and a molecular weight of 11 x 10(6). Denaturation of
      this DNA yielded two intact polynucleotide chains. Preferential binding of the
      polyribonucleotide polyuridylic-guanylic acid (poly UG) to the complementary
      strands of denatured phi29 DNA permitted separation of the strands in neutral
      CsCl gradients. In analytical CsCl density gradient centrifugation, the separated
      strands with poly UG appeared as two symmetrical bands, both heavier than the
      normal denatured DNA band. The strands differed in density by 11 mg/cc.
      Preparative separation of the phi29 DNA strands resulted in two fractions, heavy
      (H) and light (L). The H fraction was essentially free from L contamination,
      whereas L contained up to 25% of H, as determined both by rebanding the separated
      fractions in CsCl and by electron microscopic examination of self- and mixed
      annealed fractions. Pulse-labeled ribonucleic acid (RNA) prepared at intervals
      after infection was hybridized with the self-annealed DNA strands. Preliminary
      experiments indicated that both strands of phi29 DNA are transcribed during the
      development of the virus. Early transcribed phi29-specific RNA hybridizes only
      with the L strand; at later times, transcription occurs from both the L and H
      strands.

PMID- 16789129
TI  - Genetic Map of Bacteriophage phiX174.
AB  - Bacteriophage phiX174 temperature-sensitive and nonsense mutations in eight
      cistrons were mapped by using two-, three-, and four-factor genetic crosses. The
      genetic map is circular with a total length of 24 x 10(-4)wt recombinants per
      progeny phage. The cistron order is D-E-F-G-H-A-B-C. High negative interference
      is seen, consistent with a small closed circular deoxyribonucleic acid molecule
      as a genome.

PMID- 16789130
TI  - Genetic Expression in Heterozygous Replicative Form Molecules of phiX174.
AB  - Heterozygous replicative form molecules of bacteriophage phiX174 deoxyribonucleic
      acid (DNA) have been constructed in vitro. These are composed of viral strands
      extracted from purified preparations of phage bearing ts mutations and
      complementary strands of either half length or full length synthesized with
      purified DNA polymerase, in vitro, on DNA from am3 phage. In infections with such
      heterozygous DNA, involving mutations in each of four different cistrons, phage
      with the genotype of the complementary strand comprised 1 to 20% of the total
      phage produced by a spheroplast population. From single-burst analysis of the
      progeny from DNA heterozygous in one cistron (B), it appears that those phage
      with the genotype of the complementary strand arise as major components in a
      small proportion of the infected cells rather than comprising a minor component
      in most cells. The implications of such a pattern of expression are discussed
      with respect to mechanisms of phage DNA synthesis.

PMID- 16789131
TI  - Genetic and physiological studies of bacteriophage t5 I. An expanded genetic map
      of t5.
AB  - An expanded genetic map of bacteriophage T5 has been constructed by using a set
      of amber, rather than temperature-sensitive, mutants that represent 29 cistrons.
      The map consists of three small groups and one large group of genes; mutants
      defective in genes that are located in different groups exhibit maximal
      recombination when crossed with one another. However, it has been possible to
      establish tentative linkage among these groups by use of a particular mutant that
      appears to affect recombination. One of the small groups of genes is located in
      the first-step-transfer or FST segment; the other two small groups represent
      newly discovered genetic regions. The large group probably includes most or all
      of the previously published maps of T5. The apparent genetic discontinuities are
      discussed in relation to certain anatomical and physiological features that are
      unique to bacteriophage T5.

PMID- 16789132
TI  - Effect of R17 Bacteriophage-Specific Proteins on Ribosomal Ribonucleic Acid
      Synthesis of Escherichia coli.
AB  - Bacteriophage R17 and a series of amber mutants of R17 were used to infect
      cultures of Escherichia coli. The ribonucleic acid (RNA) of these cultures was
      radio-actively labeled, extracted, and subjected to polyacrylamide gel
      electrophoresis. Synthesis of ribosomal RNA was inhibited in cultures infected
      with the wild-type R17 and in cultures infected with phage mutants retaining the
      ability to produce viral polymerase. With the exception of one mutant tested, the
      degree of inhibition of ribosomal RNA synthesis in infected cells was correlated
      with the amount of viral polymerase synthesized. Maturation of 16S ribosomal RNA
      from its 17S RNA precursor appeared normal in infected cells, indicating that the
      inhibition of 16S ribosomal RNA synthesis occurred solely at the transcriptional
      level.

PMID- 16789133
TI  - Direction of Translation and Size of Bacteriophage phiX174 Cistrons.
AB  - Translation of the bacteriophage phiX174 genome follows cistron order D-E-F-G-H-A
      B-C. To establish this, the position of a nonsense mutation on the genetic map
      was compared with the physical size (molecular weight) of the appropriate protein
      fragment generated in nonpermissive cells. Distances on the phiX174 genetic map
      and distances on a physical map constructed from the molecular weights of phiX174
      proteins and protein fragments are proportional over most of the genome with the
      exception of the high recombination region within cistron A.

PMID- 16789134
TI  - Covalent linkage between ribonucleic Acid primer and deoxyribonucleic Acid
      product of the avian myeloblastosis virus deoxyribonucleic Acid polymerase.
AB  - Initiation of deoxyribonucleic acid (DNA) synthesis by the avian myeloblastosis
      virus DNA polymerase was previously suggested to involve a ribonucleic acid (RNA)
      primer, the initial product being a DNA molecule joined by a phosphodiester bond
      to the RNA primer. The existence and nature of such an RNA-DNA joint was
      investigated by assaying for transfer of a (32)P atom from an alpha-(32)P
      deoxyribonucleotide to a 2'(3')-ribonucleotide after alkaline hydrolysis of the
      polymerase product. Such a transfer was observed, but only from alpha-(32)P
      deoxyadenosine triphosphate and only to 2'(3')-adenosine monophosphate. This same
      transfer was observed in both the endogenous DNA polymerase reaction of purified
      virions and the reconstructed reaction of purified DNA polymerase plus purified
      60 to 70S viral RNA. These results indicate a high level of specificity for the
      initiation process and support the idea of a low-molecular-weight initiator RNA
      as part of the 60 to 70S RNA complex.

PMID- 16789135
TI  - Micrococcal nuclease treatment of bacteriophage heads alters the right-hand
      cohesive end of lambda deoxyribonucleic Acid.
AB  - Isolated bacteriophage lambda heads were exposed to micrococcal nuclease prior to
      addition of the phage tail. The deoxyribonucleic acid (DNA) was extracted from
      the heads and sheared to half-molecules whose cohesive ends were annealed to
      normal lambda DNA half-molecules. Melting curves of each of the cohered halves
      indicated that only the right-hand termini are altered by nuclease treatment.

PMID- 16789136
TI  - Turnip Yellow Mosaic Virus RNA as a Substrate of the Transfer RNA
      Nucleotidyltransferase II. Incorporation of Cytidine 5'-Monophosphate and
      Determination of a Short Nucleotide Sequence at the 3' End of the RNA.
AB  - Turnip yellow mosaic virus (TYMV) RNA treated with snake venom phosphodiesterase
      accepts cytidine 5'-monophosphate and adenosine 5'-monophosphate (AMP) when it is
      incubated in the presence of cytidine 5'-triphosphate (CTP), adenosine 5'
      triphosphate, and Escherichia coli transfer RNA nucleotidyltransferase; untreated
      TYMV RNA accepts only AMP. When alpha (32)PCTP was used for terminal labeling,
      the nearest neighbor analyses and the anallyses after action of various nucleases
      showed that the sequence of five nucleotides at the 3' end of TYMV RNA is:
      pGpCpApCpC. A nuclease present in commerical preparations of snake venom
      phosphodiesterase leads to the fragmentation of TYMV RNA, the 3' end of which is
      found in a fragment having a sedimentation constant close to 5s.

PMID- 16789137
TI  - Bacteriophage phi6: a Lipid-Containing Virus of Pseudomonas phaseolicola.
AB  - The purification and properties of a lipid-containing bacteriophage, phi6, are
      described. The phage contains a lipid envelope which is probably essential for
      infection. Infectivity of phi6 was lost in the presence of organic solvents,
      sodium deoxycholate, and phospholipase A. The fatty acid composition of the phage
      lipid was similar to that of the Pseudomonas phaseolicola host cells. The phage
      was composed of about 25% lipid, 13% RNA, and 62% protein. The buoyant density of
      phi6 was 1.27 g/ml in cesium chloride. The morphology of phi6 was unusual; it had
      a polyhedral head of about 60 nm surrounded by a membranous, compressible
      envelope which appeared to assume an elongated configuration upon attachment to
      pili. The adsorption rate constant was 3.3 x 10(-10) ml/min in a semi-synthetic
      medium and 3.8 x 10(-10) ml/min in a nutrient broth-yeast extract medium. The
      latent period was shorter in the former medium (80-115 min compared with 120-160
      min), and the average burst size was larger (250-400 compared with 125-150). The
      eclipse period coincided with the latent period.

PMID- 16789138
TI  - Inhibition of Protein Synthesis in Cell-Free Systems from Interferon-Treated,
      Infected Cells: Further Characterization and Effect of Formylmethionyl-tRNA(F).
AB  - The translation of encephalomyocarditis virus (EMC) RNA is markedly inhibited in
      cell-free systems from interferon-treated, vaccinia virus-infected L-cells (10,
      11). The polypeptide products synthesized in response to EMC RNA in cell-free
      systems from these and untreated infected cells have been analyzed by
      electrophoresis on polyacrylamide gels. Qualitatively, the same EMC-specific
      polypeptides were synthesized throughout. In experiments using preincubated
      microsomes from normal Krebs cells to assay cell sap from L-cells which had been
      exposed to interferon prior to infection, only the amount of the EMC-specific
      polypeptide products was reduced. This result suggests that there is an
      inhibition very early in translation in interferon-treated, infected cells.
      Initiation seems a priori the more attractive site for this inhibition, but an
      effect shortly after initiation cannot be excluded. With unfractionated cell-free
      systems from interferon-treated infected L-cells, however, there appeared to be
      an additional minor inhibitory effect on polypeptide chain elongation, in that
      the EMC-specific polypeptides synthesized showed not only a reduction in amount
      but also a bias towards lower molecular weight. The formylated methionyl
      initiator tRNA (Fmet-tRNA(F)) was used as a further probe into the apparent
      effect on intiation. With this reagent we have confirmed that there is one major
      initiation site for the translation of EMC RNA in these cell-free systems. In
      addition, the results have shown that EMC-specific polypeptide chains initiated
      with Fmet escape the major interferon-mediated inhibition at or shortly after
      initiation.

PMID- 16789139
TI  - Acquisition of new DNA sequences after infection of chicken cells with avian
      myeloblastosis virus.
AB  - DNA-RNA hybridization studies between 70S RNA from avian myeloblastosis virus
      (AMV) and an excess of DNA from (i) AMV-induced leukemic chicken myeloblasts or
      (ii) a mixture of normal and of congenitally infected K-137 chicken embryos
      producing avian leukosis viruses revealed the presence of fast- and slow
      hybridizing virus-specific DNA sequences. However, the leukemic cells contained
      twice the level of AMV-specific DNA sequences observed in normal chicken
      embryonic cells. The fast-reacting sequences were two to three times more
      numerous in leukemic DNA than in DNA from the mixed embryos. The slow-reacting
      sequences had a reiteration frequency of approximately 9 and 6, in the two
      respective systems. Both the fast- and the slow-reacting DNA sequences in
      leukemic cells exhibited a higher T(m) (2 C) than the respective DNA sequences in
      normal cells. In normal and leukemic cells the slow hybrid sequences appeared to
      have a T(m) which was 2 C higher than that of the fast hybrid sequences.
      Individual non-virus-producing chicken embryos, either group-specific antigen
      positive or negative, contained 40 to 100 copies of the fast sequences and 2 to 6
      copies of the slowly hybridizing sequences per cell genome. Normal rat cells did
      not contain DNA that hybridized with AMV RNA, whereas non-virus-producing rat
      cells transformed by B-77 avian sarcoma virus contained only the slowly reacting
      sequences. The results demonstrate that leukemic cells transformed by AMV contain
      new AMV-specific DNA sequences which were not present before infection.

PMID- 16789140
TI  - Detection of a protein of avian leukoviruses in uninfected chick cells by
      radioimmunoassay.
AB  - A radioimmunoassay (RIA) has been used to measure the quantity of protein P27
      (mol wt 27,000; group specific-1 [gs-1]) of avian leukoviruses in different types
      of chicken embryos and tissues of adult chickens. The RIA used was 200- to 300
      fold more sensitive than the complement fixation test and was able to detect as
      little as 0.3 ng of P27. Among six embryos tested, which are negative for gs
      antigen by the complement fixation test, P27 was undetectable in three embryos,
      but another three contained about 5 ng of P27 per mg of cell protein by RIA. The
      amount of P27 in gs antigen-positive cells ranged from 22 to 57 ng per mg of cell
      protein. P27 was found in liver, lung, ovary, feather pulp, and spleen from adult
      gs antigen-positive chickens. This protein was undetectable in various tissues
      from gs antigen-negative chickens.

PMID- 16789141
TI  - Genetic recombination for antigenic markers of antigenically different strains of
      influenza B virus.
AB  - Incorporation of trypsin in agar overlay or fluid maintenance media resulted in
      enhancement of plaquing efficiency and replication of influenza B viruses in
      primary chicken embryo fibroblasts. Using this improved technique, recombination
      was attempted with two serologically distinct strains of influenza B virus,
      B/Lee/40 and B/Massachusetts/1/71. After mixed infection, two virus clones were
      selected and characterized in detail. Hemagglutination inhibition and
      neuraminidase inhibition tests showed that these viruses are reciprocal antigenic
      recombinants with hemagglutinin derived from one parent and neuraminidase from
      the other. Serological examinations of the antisera to these recombinants
      confirmed the results. The frequency of recombination was high in the present
      system and 64% of the virus clones isolated without selection from the mixed
      yield were recombinants. This high recombination frequency is consistent with the
      genomic reassortment that is characteristic of recombination of influenza A
      viruses.

PMID- 16789142
TI  - Stimulation of cellular DNA synthesis by human cytomegalovirus.
AB  - Human cytomegalovirus (CMV) is able to induce cellular DNA synthesis in both
      permissive (human embryonic lung) and nonpermissive (Vero) cells. The induction
      of cell DNA synthesis was assayed by the incorporation of [methyl-(3)H]thymidine
      into macromolecules having the buoyant density characteristics of cell DNA. The
      DNA synthesis induced by CMV infection appears to represent normal
      semiconservative replication as opposed to repair synthesis. Both strains of CMV
      tested were capable of inducing cell DNA synthesis. Virus exposed to heat or UV
      light prior to infection lost the ability to induce DNA synthesis, indicating
      that a virus-coded function expressed after infection is responsible for
      stimulation of cell DNA synthesis.

PMID- 16789143
TI  - Marine transducing bacteriophage attacking a luminous bacterium.
AB  - The isolation and partial characterization of a marine bacteriophage attacking a
      strain of luminous bacteria is described, including some physical, biological,
      and genetic properties. It is a DNA phage of density of 1.52 with a long flexible
      tail and an apparently icosohedral head. With respect to stability in suspension,
      it has a rather specific requirement for the sodium ion in high concentration; it
      is further stabilized by the addition of calcium and magnesium ions. These same
      ions are likewise all required for both good plating efficiency and plaque
      uniformity. Although it goes through a typical lytic growth cycle (about 45 min),
      with a burst size of 100, and no stable lysogens have been isolated, it is
      nevertheless a transducing phage specifically for the tryptophan region,
      transducing several, but not all, independently isolated Trp(-) auxotrophs to
      protrophy. No other auxotrophs of a variety of amino acids were transduced by
      this phage to prototrophy. Phage infection does not change the normal expression
      of the luminescent system, and light remains at near normal levels until cell
      lysis occurs.

PMID- 16789145
TI  - Blocked and unblocked 5' termini in reovirus genome RNA.
AB  - Uniformly (32)P-labeled, double-stranded genome RNA isolated from purified
      reovirus contains two types of 5'-terminal sequences. One strand contains a
      phosphatase-resistant 5'-terminal structure, XpppG(*)pCpU, which is also present
      in the viral mRNA. The 5' blocking group, X, is removed by beta-elimination
      indicating that it is a nucleoside containing free 2',3'-hydroxyls. G(*)pC is an
      alkaline-resistant, 2'-O-methylated sequence. The other strand contains a
      phosphatase-sensitive 5' sequence, ppGpPupPyp. The results are discussed in
      relation to blocked 5'-terminal structures in other viral and cellular RNAs.

PMID- 16789144
TI  - Genetic Analysis of Adenovirus Type 2 II. Preliminary Phenotypic Characterization
      of Temperature-Sensitive Mutants.
AB  - The properties of temperature-sensitive mutants of adenovirus type 2 representing
      12 complementation groups were studied. All mutants were normal with respect to
      adsorption as measured by viral inclusion formation and viral DNA synthesis as
      shown by velocity sedimentation in alkaline sucrose gradients. One mutant,
      however, formed viral inclusions of altered morphology at the nonpermissive
      temperature. The synthesis of the major capsid proteins was examined by
      immunodiffusion. On this basis, the complementation groups could be arranged as
      follows: (i) one group was negative for all three proteins; (ii) three groups
      failed to synthesize penton bases; (iii) eight groups were positive for hexons,
      pentons, and fibers. The assembly of virus particles at 39 C was examined by
      equilibrium sedimentation in CsCl; three groups were found defective, whereas two
      of the penton-negative groups were positive for virion production. Tests of the
      thermolability of virions at 50 C revealed eight groups labile whereas the
      remainder were insensitive to heat inactivation. None of five mutants inoculated
      in newborn rats induced tumors, although three of them were capable of in vitro
      transformation.

PMID- 16789146
TI  - DNase Specific for Uracil-Containing Bacteriophage DNA.
AB  - A DNase from Bacillus subtilis which specifically hydrolyzes native DNA of phage
      PBS 1 has been purified and characterized. The mode of action of the enzyme is
      endonucleolytic, yielding deoxyuridine and oliogonucleotides of various sizes.
      The primary site of enzymatic attack is deoxyuridylic acid in the DNA. A mild
      nitrous acid treatment of thymine-containing thymus DNA, which deaminates 30% of
      the cytosine residues, renders the DNA susceptible to the DNase. Nicked DNA from
      coli phage T5 and hydroxymethyluracil-containing DNA from phage PBS 15 are not
      sensitive to this DNase.

PMID- 16789147
TI  - New Late Gene, dar, Involved in DNA Replication of Bacteriophage T4 I. Isolation,
      Characterization, and Genetic Location.
AB  - Suppressors of gene 59-defective mutants were isolated by screening spontaneous,
      temperature-sensitive (ts) revertants of the amber mutant, amC5, in gene 59. Six
      ts revertants were isolated. No gene 59-defective ts recombinant was obtained by
      crossing each ts revertant with the wild type, T4D. However, suppressors of gene
      59-defective mutants were obtained from two of these ts revertants. These
      suppressor mutants are referred to as dar (DNA arrested restoration). dar mutants
      specifically restored the abnormalities, both in DNA synthesis and burst size,
      caused by gene 59-defective mutants to normal levels. It is unlikely that dar
      mutants are nonsense suppressors since they failed to suppress amber mutations in
      11 other genes investigated. The genetic expression of dar is controlled by gene
      55; therefore, dar is a late gene. The genetic location of dar has been mapped
      between genes 24 and 25, a region contiguous to late genes. dar appears to be
      another nonessential gene of T4 since burst sizes of dar were almost identical to
      those of the wild type. Mutations in dar did not affect genetic recombination and
      repair of UV-damaged DNA, but caused a sensitivity to hydroxyurea in progeny
      formation. The effect of the dar mutation on host DNA degradation cannot account
      for its hydroxyurea sensitivity. dar mutant alleles were recessive to the wild
      type allele as judged by restoration of arrested DNA synthesis. The possible
      mechanisms for the suppression of defects in gene 59 are discussed.

PMID- 16789148
TI  - Temperate Bacteriophage Which Causes the Production of a New Major Outer Membrane
      Protein by Escherichia coli.
AB  - Under most conditions of growth, the most abundant protein in the outer membrane
      of most strains of Escherichia coli is a protein designated as "protein 1" or
      "matrix protein". In E. coli B, this protein has been shown to be a single
      polypeptide with a molecular mass of 36,500 and it may account for more than 50%
      of the total outer membrane protein. E. coli K-12 contains a very similar,
      although probably not identical, species of protein 1. Some pathogenic E. coli
      strains contain very little protein 1 and, in its place, make a protein
      designated as protein 2 which migrates faster on alkaline polyacrylamide gels
      containing sodium dodecyl sulfate and which gives a different spectrum of CNBr
      peptides. An E. coli K-12 strain which had been mated with a pathogenic strain
      was found to produce protein 2, and a temperate bacteriophage was isolated from
      this K-12 strain after induction with UV light. This phage, designated as PA-2,
      is similar in morphology and several other properties to phage lambda. When
      strains of E. coli K-12 are lysogenized by phage PA-2, they produce protein 2 and
      very little protein 1. Adsorption to lysogenic strains grown under conditions
      where they produce little protein 1 and primarily protein 2 is greatly reduced as
      compared to non-lysogenic strains which produce only protein 1. However, when
      cultures are grown under conditions of catabolite repression, protein 2 is
      reduced and protein 1 is increased, and lysogenic and non-lysogenic cultures
      grown under these conditions exhibit the same rate of adsorption. Phage PA-2 does
      not adsorb to E. coli B, which appears to have a slightly different protein 1
      from K-12. These results suggest that protein 1 is the receptor for PA-2, and
      that protein 2 is made to reduce the superinfection of lysogens.

PMID- 16789149
TI  - Expression of the Major Viral Glycoprotein of Avian Tumor Virus in Cells of
      chf(+) Chicken Embryos.
AB  - The expression of gp85, the major viral glycoprotein of avian tumor virus, by
      certain chicken embryonic cells was studied by the use of sera directed to
      antigenic determinants of subgroup E viral gp85. As analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of immune precipitates prepared with
      lysates of cells that had been labeled with [(3)H]glucosamine, chf(+) chicken
      embryo cells synthesize molecules of gp85 which possess type and probably also
      group antigenic specificities. Under similar conditions of analysis, no gp85 or
      antigenically related components could be detected in lysates of chf(-) cells.

PMID- 16789150
TI  - Chromatographic Separation and Antigenic Analysis of Proteins of the
      Oncornaviruses IV. Biochemical Typing of Murine Viral Proteins.
AB  - Tryptic peptide maps were prepared for four purified structural proteins derived
      from several murine leukemia viruses (MuLV's). Analyses of these peptide maps
      reveal that the p30 proteins of Rauscher, Moloney, and Gross MuLV's are very
      similar to each other, as are the p10's obtained from these three viruses. In
      contrast, the peptide maps of the individual p15's and p12's from the same
      viruses establish that each of these polypeptides is highly strain specific. For
      all four polypeptides studied, unique peptides appear in the Rauscher MuLV and
      Moloney MuLV tryptic profiles that are not present in the corresponding Gross
      MuLV profile. By this method of analysis it was possible to distinguish the p30's
      of N-tropic and B-tropic MuLV's derived from the same BALB/c mouse.

PMID- 16789151
TI  - Interactions of Polyoma and Mouse DNAs III. Mechanism of Polyoma Pseudovirion
      Formation.
AB  - In primary mouse kidney cell cultures infected with polyoma virus, the processes
      leading to virion and pseudovirion formation were studied. By photometric DNA
      quantitation, we followed the kinetics of mouse and polyoma DNA synthesis and the
      formation of low-molecular-weight fragmented mouse DNA (mouse f-DNA). Virus was
      harvested at different times and analyzed for its proportion of pseudovirions.
      The following correlations between the intracellular events and the production of
      virions and pseudovirions were found. (i) Syntheses of cellular and viral DNA
      were closely linked, both in time and in rates of synthesis. (ii) An increase of
      mouse f-DNA could only be detected several hours after the onset of mouse and
      polyoma DNA replication; its formation coincided in time with the appearance of
      progeny virus. (iii) The proportion of pseudovirions was not dependent on the
      amount of mouse f-DNA formed, but seemed to be inversely related to the amount of
      viral DNA synthesized. This was borne out by experiments in which DNA synthesis
      was partially inhibited by mitomycin C or after a synchronized onset of DNA
      replication. Under these conditions, virus preparations with a two- to threefold
      increased proportion of pseudovirions were obtained as compared with those from
      uninhibited cultures. Virus isolated from the remaining monolayer always had a
      higher proportion of pseudovirions than virus isolated at the same time from the
      supernatant medium only; also, the proportion of pseudovirions increased slightly
      with time after infection. Thus, according to the experimental conditions used,
      polyoma virus preparations with a low (10 to 20%) or a high (60 to 80%)
      proportion of pseudovirions can be obtained.

PMID- 16789152
TI  - Marek's Disease Herpesviruses I. Production and Preliminary Characterization of
      Marek's Disease Herpesvirus A Antigen.
AB  - A method was developed for the large-scale production of Marek's disease
      herpesvirus A antigen in duck embryo fibroblast roller bottle cultures in
      quantities sufficient to permit its purification and characterization. Maximum
      yield was obtained in serum-free culture medium harvested daily. The Marek's
      disease herpesvirus A antigen was stable at pH 2.0 and was a glycoprotein based
      on its sensitivity to trypsin, specific immune co-precipitation of radioactive
      amino acids and glucosamine, and detection of radioactive glucosamine by
      immunodiffusion and autoradiography. The antigen aggregated and lost titer upon
      storage but dissociated readily and regained titer in 1 or 2 M urea and 0.05%
      Brij 35. Fresh unaggregated antigen or antigen dissociated with urea and Brij 35
      sedimented at 3.7S on sucrose gradients. The apparent molecular weight of the
      glycoprotein antigen was estimated to be 44,800 by gel filtration on Sephadex G
      200 in the presence of 2 M urea and 0.05% Brij 35.

PMID- 16789153
TI  - Marek's Disease Herpesviruses II. Purification and Further Characterization of
      Marek's Disease Herpesvirus A Antigen.
AB  - Marek's disease herpesvirus A antigen was purified greater than 200-fold with a
      24% recovery by ion exchange column chromatography, isoelectric focusing, and
      preparative polyacrylamide gel electrophoresis. The antigen had an isoelectric
      point of 6.68 +/- 0.03 in the presence of 1 M urea and 0.05% Brij 35, a nonionic
      detergent, and approximately 6.5 in the absence of dissociating agents. When
      analyzed by electrophoresis on analytical polyacrylamide gels, the purified
      antigen migrated as a single broad band which stained for both protein and
      carbohydrate, suggesting that it was a highly purified heterogeneous
      glycoprotein. However, the antigen was not purified to homogeneity as determined
      by electrophoresis on polyacrylamide gels in the presence of sodium dodecyl
      sulfate and by immunodiffusion analysis. Antibody to Marek's disease herpesvirus
      A antigen was prepared in a rabbit, and antibody to two contaminating antigens
      was removed by adsorption to yield monospecific antisera.

PMID- 16789154
TI  - Simian virus 40 DNA segment of the adenovirus 7-simian virus 40 hybrid, e46, and
      its transcription during permissive infection of monkey kidney cells.
AB  - Nucleic acid hybridization methodology has been used to investigate the span of
      the simian virus 40 (SV40) DNA segment in the adenovirus 7-SV40 hybrid, E46(+),
      and the extent of its transcription in lytically infected monkey kidney cells.
      The SV40 segment of E46(+) comprises approximately 62% of the SV40 genome; it
      originates in the proximal region of Hin-G (the G fragment derived by cleavage of
      intact SV40 DNA with Haemophilus influenzae restriction endonuclease), extends
      sequentially through approximately 80% of this fragment, all of fragments Hin-B, 
      I, -H, and -A, and terminates approximately 70% of the distance through Hin-C.
      During E46(+) lytic infection of permissive cells, the vast majority of stable
      cytoplasmic SV40-specific RNA is transcribed from the minus (E) strand of the
      fragments Hin-A, -H, -I, and -B, comprising the early template region.
      Transcripts of the minus strand of the Hin-G and -C fragments are detected in
      much lower concentrations, especially in the total lytic cellular RNA, whereas
      RNA complementary to the plus (L) strand is not detected. The transcriptional
      pattern of the SV40 segment within E46(+) is thus very similar to that in a
      number of transformed cell lines and in some respects to the transcriptional
      pattern in a series of nondefective adenovirus 2-SV40 hybrid viruses. These
      results suggest a common transcriptional mechanism for integrated SV40 DNA.

PMID- 16789155
TI  - Properties of visna virus particles harvested at short time intervals: RNA
      content, infectivity, and ultrastructure.
AB  - The major RNA component of Visna virus harvested at short intervals of time (5
      min) is not the 60 to 70S RNA but a molecule of higher electrophoretic mobility.
      This RNA has been isolated and characterized. Its sedimentation coefficient is
      identical to that of 30 to 40S RNA subunits obtained by heat denaturation of the
      60 to 70S RNA. In 1.8% acrylamide gels without agarose the electrophoretic
      mobility of 30 to 40S RNA subunits present in rapidly harvested virus is slightly
      lower than that of the subunits obtained by denaturation of the 60 to 70S RNA;
      after heat denaturation the mobilities are identical. These free RNA subunits
      present in early virus particles assemble into a 60 to 70S RNA complex as shown
      by following the RNA content of early virus incubated at 37 C for various lengths
      of time. The rate of this maturation process is slow. There is no difference
      between the infectivity of immature and mature virus particles. Both particles
      have a dense core when examined in sections of virus pellets.

PMID- 16789156
TI  - Complete and Defective Bacteriophages of Classical Vibrio cholerae: Relationship
      to the Kappa Type Bacteriophage.
AB  - The Classical Vibrio cholerae strain NIH 41 contains two temperate
      bacteriophages, designated VcA-1 and VcA-2, that are distinguished by immunity,
      plaque morphology, induction kinetics, and particle morphology. Both phage are
      serologically related to phage Kappa. However, only phage VcA-2 has the Kappa
      type host range and immunity. The induction kinetics and immunity patterns of
      Classical vibrios suggest that these strains may contain defective phage related
      to the phages isolated from NIH 41. Classical strain 569B releases phage-tail
      structures upon induction that are morphologically and serologically related to
      both phages VcA-1 and VcA-2. The possible reason for the defectiveness of these
      phages in 569B is discussed. It is concluded that complete or defective
      bacteriophages of the Kappa type morphology and serology are extremely prevalent
      in V. cholerae, regardless of biotype.

PMID- 16789157
TI  - Morphology of BHK-21 Cells Infected with Sindbis Virus Temperature-Sensitive
      Mutants in Complementation Groups D and E.
AB  - BHK-21 cells infected with temperature-sensitive mutants of Sindbis virus in
      complementation groups D and E differed in their appearance under nonpermissive
      conditions. Cells infected at nonpermissive temperature with virus defective in
      complementation group E had nucleocapsids attached in large numbers to the inside
      surface of the host plasma membrane. Infection with a group D mutant produced
      nucleocapsids that did not attach to the plasma membrane but rather remained free
      in the cell cytoplasm.

PMID- 16789158
TI  - Structure of the DNA of the adenovirus 7-simian virus 40 hybrid, e46, by electron
      microscopy.
AB  - The DNA molecule of the adenovirus 7-simian virus (SV) 40 hybrid, E46(+),
      contains a single substitution of SV40 DNA located about 0.05 adenovirus 7
      lengths from one end (arbitrarily designated the left end). The left to right
      direction in the SV40 DNA segment of the hybrid corresponds to the clockwise
      direction in the SV40 physical map. The left end point of the segment maps at
      about SV40 map position 0.50 +/- 0.01 and the right end point at about SV40 map
      position 0.66 +/- 0.01. The region between SV40 map positions 0.71 and 0.11
      (clockwise) is deleted. Thus, the region between SV40 map position 0.50 and 0.66
      (clockwise) is repeated in tandem.

PMID- 16789159
TI  - Effect of UV Light on RNA-Directed DNA Polymerase Activity of Murine
      Oncornaviruses.
AB  - The UV inactivation of RNA-directed DNA polymerase activity of Rauscher leukemia
      virus was shown to be due to damage to the protein. The UV dose resulting in 37%
      survival of viral polymerase activity at 254 nm was 2.4 x 10(4) to 3.1 x 10(4)
      ergs/mm(2). The inactivation rate of p30, a major internal viral protein, was
      much slower.

PMID- 16789160
TI  - Heteroduplex mapping of heat-resistant deletion mutants of bacteriophage t5.
AB  - The bacteriophage T5 is known to spontaneously generate deletion mutants (st
      mutants) exhibiting enhanced resistance to heat inactivation in citrate buffer. A
      series of such mutants has been isolated and the deletions visualized by electron
      microscopy of heteroduplex molecules. The deletions are found to cluster in one
      region of the chromosome.

PMID- 16789161
TI  - Inhibition of DNA polymerase from herpes simplex virus-infected wi-38 cells by
      phosphonoacetic Acid.
AB  - Infection of Wi-38 cells with herpes simplex virus induced an elevated DNA
      polymerase activity which had many biochemical properties different from normal
      cell DNA polymerase. Phosphonoacetic acid specifically inhibited the virus
      induced DNA polymerase as compared to the normal WI-38 cell DNA polymerase. The
      compound did not appear to inhibit enzyme activity by interacting with the DNA
      primer.

PMID- 16789162
TI  - Polyamines in type 5 adenovirus-infected cells and virions.
AB  - The incorporation of l-[(14)C]ornithine and [(14)C]putrescine into putrescine,
      spermidine, and spermine in type 5 adenovirus-infected KB cells was identical to
      that in uninfected control cells early in infection, but incorporation into
      putrescine stopped after 8 to 12 h and the rate of incorporation into spermidine
      was reduced between 12 and 20 h after infection. The amount of polyamines found
      associated with purified virus could neutralize a maximum of 3 to 4% of the virus
      DNA, but the small quantities of polyamines detected could not be distinguished
      from nonspecific binding of polyamines to virions. These data suggest that
      polyamines are probably not integral components of adenovirus particles.

PMID- 16789163
TI  - Isolation of infectious xenotropic mouse type C virus by transfection of a
      heterologous cell with DNA from a transformed mouse cell.
AB  - An endogenous xenotropic type C virus has been isolated from a Kirsten sarcoma
      virus-transformed BALB/c mouse cell line by transfection of a mink fibroblast
      cell with the DNA from the transformed cells. The results indicate that
      transfection may be used as a technique to isolate this endogenous type C virus
      without the need to chemically induce the cell line containing the provirus prior
      to attempting to isolate the virus.

PMID- 16789164
TI  - Attachment of a long-tailed Rhizobium bacteriophage to the pili of its host.
AB  - Bacterial strain 16-12 was isolated from the root nodules of lupines and was
      found to be mitomycin C-inducible for the production of a bacteriophage ("16-12
      1") with a long noncontractile tail. The phage was found to attach with a fork
      like terminal tail structure to the pili of strain 16-12. In addition, it was
      also found adsorbed to the bacterial cell poles. It is suggested that phage 16-12
      1 may be pilus dependent.

PMID- 16789165
TI  - Biochemical and biophysical properties of hyphomicrobium bacteriophage hyphi30.
AB  - Hyphomicrobium bacteriophage Hyphi30 and its nucleic acid were studied to
      determine some of their biochemical and biophysical properties. The molecular
      weight of the phage is 55.4 x 10(6), and its buoyant density is 1.508 g/ml. The
      nucleic acid of Hyphi30 is linear, double-stranded DNA with a molecular weight of
      29.7 x 10(6). The guanine-plus-cytosine content of the DNA was 62% as determined
      from its melting temperature and buoyant density.

PMID- 16789166
TI  - In vitro synthesis of turnip yellow mosaic virus coat protein in a wheat germ
      cell-free system.
AB  - Turnip Yellow Mosaic Virus RNA directs the synthesis in vitro of its coat protein
      in a wheat germ cell-free extract. Optimum conditions for synthesis have been
      defined, and the effect of spermine on specifically enhancing coat protein
      formation has been examined. Identity between the in vitro synthesized coat
      protein and authentic coat protein of Turnip Yellow Mosaic Virus was established
      by analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, peptide
      mapping, and immunoprecipitation.

PMID- 16789167
TI  - Effect of alkaline protease on the antigenic nature of wiseana nuclear
      polyhedrosis virus polyhedron protein.
AB  - Polyhedron protein from Wiseana spp. nuclear polyhedrosis virus was found to be
      degraded by an alkali protease when polyhedra are dissolved in alkali. The
      protease activity did not occur at high pH (0.1 M NaOH) and was inactivated by
      heating polyhedra to 70 degrees C for 3 h. The products from the protease
      degradation of Wiseana spp. nuclear polyhedrosis virus polyhedron protein retain
      the antigenicity of undegraded polyhedron protein as measured by the direct solid
      phase radioimmunoassay and immunoadsorption. Degradation products below 27,000
      daltons could not be detected by the sandwich radioimmunoassay, indicating that
      they are probably monovalent.

PMID- 16789168
TI  - Complex of Virus-Like Particles Containing Double-Stranded RNA from Thielaviopsis
      basicola.
AB  - Six randomly selected isolates of Thielaviopsis basicola were found to contain
      spherical virus-like particles (VLPs) approximately 40 nm in diameter. One
      isolate, ATCC 34114, selected for further analysis contained a complex of VLPs
      that sedimented as eight or more bands in sucrose density gradients and contained
      five size classes of double-stranded RNA. Five discrete precipitation lines were
      obtained in immunoelectrophoresis, which indicated that this isolate of T.
      basicola contains five distinct species of VLPs.

PMID- 16789169
TI  - Alkaline protease associated with virus particles of a nuclear polyhedrosis
      virus: assay, purification, and properties.
AB  - Proteolytic activity was detected within polyhedra of the nuclear polyhedrosis
      virus of Spodoptera littoralis. The enzyme activity was detected by its ability
      to degrade the major structural polypeptide of polyhedra (polyhedrin). A
      quantitative assessment of activity was made by a radioassay technique using (3)H
      labeled polyhedrin as the substrate. Of the structural components of polyhedra,
      virus particles showed the greatest specific proteolytic activity. Preparations
      of purified nucleocapsids were inactive. The virus particle enzyme displayed a
      temperature optimum for proteolysis of 30 to 40 degrees C and a pH optimum of
      9.6. Its activity was inhibited by H(2+) and Cu(2+), but not by 2
      mercaptoethanol. The enzyme was purified from detergent-treated virus particles
      by affinity column chromatography, using polyhedrin linked to cyanogen bromide
      activated Sepharose. Three major envelope polypeptides (L107, L85, and L71) bound
      to the column at 4 degrees C, but after incubation at 31 degrees C, polypeptide
      L71 alone was eluted. The fractions containing this protein exhibited a specific
      enzyme activity more than 80-fold greater than that present in polyhedra. The
      possible significance of the alkaline protease, and other proteins with affinity
      for polyhedrin, is discussed.

PMID- 16789170
TI  - Characterization of the 3' Termini of the RNAs of Cowpea Mosaic Virus.
AB  - A sequence of polyadenylic acid, homogeneous in composition but heterogeneous in
      length, was isolated from complete pancreatic RNase digests of both middle and
      bottom RNAs of cowpea mosaic virus. The polyadenylic acid was 3'-terminal and
      occurred once per molecule. A fragment consisting of the polyadenylic acid and
      approximately the next 25 nucleotides could be isolated from complete T1 RNase
      digests of either RNA. The region adjacent to the polyadenylic acid in both RNAs
      was rich in pyrimidines. The mobilities of the fragments in 12.4% polyacrylamide
      8 M urea gels were used to estimate their lengths and to calculate number average
      and weight average molecular weights.

PMID- 16789171
TI  - Herpesvirus salmonis: Characterization of a New Pathogen of Rainbow Trout.
AB  - A new agent, provisionally designated Herpesvirus salmonis, was isolated from
      post-spawning rainbow trout (Salmo gairdneri) and studied primarily in the RTG-2
      rainbow trout cell line. Infection of RTG-2 cells resulted in the formation of
      syncytia and Cowdry type A intranuclear inclusions. Replication occurred
      regularly at 5 and 10 degrees C, but was inconsistent at 15 degrees C, largely
      inhibited at 0 degrees C, and completely inhibited at 20 degrees C or higher. The
      virus was acid, heat, ether, and chloroform labile, but stable to freezing and
      thawing. It did not hemagglutinate. Viral DNA had a buoyant density of 1.709
      g/cm(3) and a guanine-cytosine value of 50%. Hexagonal nucleocapsids had a
      diameter of 90 nm and were first seen in nuclei at 36 h. Enveloped forms measured
      about 150 nm and occurred both cytoplasmically and extracellularly. At 10 degrees
      C, a one-step growth culture required about 96 h; cell-associated virus peaked at
      about 10(5) PFU/ml and exceeded released virus by a factor of about 10.

PMID- 16789172
TI  - In Vitro Replication of Cowpea Mosaic Virus RNA III. Template Recognition by
      Cowpea Mosaic Virus RNA Replicase.
AB  - Cowpea mosaic virus (CPMV) RNA replicase has been purified about 200-fold from
      CPMV-infected Vigna unguiculata leaves. Optimal reaction conditions for replicase
      activity have been established that allow RNA synthesis to proceed for at least
      15 h. Using a polymerase assay under conditions optimal for CPMV RNA-directed RNA
      synthesis, all natural RNA species tested appeared to be able to direct the
      incorporation of labeled ribonucleotides, whereas synthetic homoribopolymers were
      either inactive or only slightly active. Using a nitrocellulose membrane filter
      assay to measure complex formation between the replicase preparation and various
      RNA species, all natural RNA species tested, except that of the comovirus radish
      mosaic virus, appeared to be unable to compete with (32)P-labeled CPMV RNA in
      binding to replicase. We propose that CPMV replicase is actually template
      specific but does not display this property in a polymerase assay, since labile
      complexes between heterologous templates and replicase become stabilized by the
      formation of phosphodiester bonds. From homoribopolymer competition binding
      experiments we conclude that the polyadenylic acid on the CPMV genome might be a
      part of the replicase binding site.

PMID- 16789173
TI  - Factors Influencing the Production of Intermediate Particles During Alkaline
      Degradation of Tobacco Mosaic Virus: Time, pH, Salt Concentration, and
      Temperature.
AB  - Kinetic analysis of the alkaline degradation of tobacco mosaic virus revealed
      degradation to be a stepwise process during which five distinct intermediate
      nucleoprotein particles were formed. Each intermediate accumulated before being
      degraded to the next smaller particle. After prolonged exposure to alkali, a
      stable nucleoprotein particle accumulated. The rate of alkaline degradation of
      tobacco mosaic virus was retarded by lowering pH (10.3 to 9.0), increasing salt
      concentration (0 to 100 mM), or increasing incubation temperature over the range
      of 0 to 22 degrees C. A fraction (15 to 25%) of the total virus population
      appeared to be completely resistant to alkaline degradation; however, the progeny
      of this virus fraction was sensitive to alkaline degradation.

PMID- 16789174
TI  - Effect of cordycepin triphosphate on in vitro RNA synthesis by plant viral
      replicases.
AB  - In vitro RNA synthesis by tobacco mosaic virus and cowpea chlorotic mottle virus
      replicase were inhibited by cordycepin triphosphate. Inhibition could be overcome
      with higher concentrations of ATP in assay mixtures but not with UTP. Products
      synthesized in vitro by tobacco mosaic virus RNA replicase in the presence of
      inhibitor revealed replicative form but not replicative intermediate RNAs. These
      results suggest that cordycepin triphosphate competes specifically with ATP and
      results in premature termination of viral RNA synthesis in vitro.

PMID- 16789175
TI  - Physical Map of the DNA Genome of Autographa californica Nuclear Polyhedrosis
      Virus.
AB  - A physical map of the 88 x 10(6) dalton, circular DNA genome of Autographa
      californica nuclear polyhedrosis virus was constructed. The complete order of
      BamHI and XmaI restriction enzyme sites was determined. The EcoRI and HindIII
      fragments were partially ordered, and their general locations, relative to the
      BamHI and XmaI maps, were determined. Alterations in the restriction endonuclease
      fragment patterns of natural genotypic variants of A. californica nuclear
      polyhedrosis virus, including Trichoplusia ni MEV nuclear polyhedrosis virus,
      were located on the physical map. Alterations were found throughout the A.
      californica nuclear polyhedrosis virus DNA genome.

PMID- 16789177
TI  - Characterization of EV-2, a Virus Isolated from European Eels (Anguilla anguilla)
      with Stomatopapilloma.
AB  - A virus designated EV-2 has been isolated from external tumor tissue and internal
      organs of European eels (Anguilla anguilla) with stomatopapilloma. It contains
      RNA and is ether, acid, and temperature labile above 4 degrees C, and
      concentrated preparations agglutinate chicken and sheep erythrocytes. The
      addition of actinomycin D during the first 2.75 h of infection inhibits viral
      replication. As determined in sucrose gradients, the buoyant density of the virus
      is 1.19 g/cm(3). EV-2 has a moderately pleomorphic spherical morphology; its
      diameter ranges from 80 to 140 nm. The virion has narrow, regularly spaced
      surface projections about 10 nm long. Replication in FHM cells at 15 degrees C
      shows new infectivity appearing at 10 h postinfection and reaching a plateau at
      20 h. Cytopathic effects consist of cell fusion, syncytia, and irregularly
      rounded cell masses. Viral antigen was detected in the cytoplasm of infected
      cells by specific immunofluorescence.

PMID- 16789176
TI  - Unusual Baculovirus of the Parasitoid Wasp Apanteles melanoscelus: Isolation and
      Preliminary Characterization.
AB  - A baculovirus present in the female reproductive tract of the parasitoid wasp
      Apanteles melanoscelus has been isolated and partially characterized. Viral DNA
      is double stranded, circular, and of highly variable molecular weight ranging
      from 2 x 10(6) to 25 x 10(6); the DNA is of homogeneous density at rho = 1.694
      g/ml. Acrylamide gels resolve 18 polypeptide bands in the case of purified
      virions; four to five of these appear in a semipurified nucleocapsid preparation.
      The electrophoretic profiles obtained are compared with those of two other
      baculoviruses.

PMID- 16789178
TI  - 5'-terminal sequences of spring viremia of carp virus RNA synthesized in vitro.
AB  - Sequence analyses have been undertaken on the 5' termini of the RNA species
      synthesized in vitro at 22 degrees C by Spring viremia of carp virion (SVCV)
      associated transcriptase by using virus grown in mammalian BHK-21 cells. SVCV
      product RNA was synthesized in the absence or presence of low (0.56 muM) or high
      (0.8 mM) concentrations of added S-adenosyl-l-methionine (SAM). Two major
      sequences obtained in the absence (or in low concentrations) of SAM have been
      shown to be GpppAp and GpppAmpAp(C). A minor sequence detected when a low
      concentration of [(3)H]SAM was added to reaction mixtures was 7mGpppAmpAp. Larger
      quantities of the 7mGpppAmpAp(C) sequence, in addition to the GpppAmpAp(C)
      sequence, were obtained when high concentrations of SAM were used, and under
      these conditions no GpppAp sequences were detected. It has further been shown
      that with low concentrations of [(3)H]SAM the principle in vitro methylation of
      adenosine in SVCV product RNA occurred at the 2'-O-ribose position; no
      methylation at the N(6)-adenosine position and no internal product RNA
      methylation were detected. Comparison of the SVCV results to the published data
      on the 5'-terminal structures of the in vitro or in vivo mRNA species of
      vesicular stomatitis virus Indiana and vesicular stomatitis virus New Jersey
      suggests that the 5' sequences of transcript RNA of different rhabdoviruses may
      have been conserved.

PMID- 16789179
TI  - Restriction Maps of Five Autographa californica MNPV Variants, Trichoplusia ni
      MNPV, and Galleria mellonella MNPV DNAs with Endonucleases SmaI, KpnI, BamHI,
      SacI, XhoI, and EcoRI.
AB  - The restriction sites of Autographa californica nuclear polyhedrosis virus
      (AcMNPV) E2 DNA were mapped for the endonucleases SmaI, KpnI, BamHI, SacI, XhoI,
      and EcoRI. The restriction maps of four other AcMNPV variants, Trichoplusia ni
      (TnMNPV), and Galleria mellonella (GmMNPV) genomes were determined and compared
      to the endonuclease cleavage maps of AcMNPV E2 DNA. The viral structural
      polypeptides of AcMNPV variants S3, E2, S1, M3, and R9 were the same when
      analyzed by polyacrylamide gel electrophoresis. The major structural polypeptides
      of GmMNPV and TnMNPV had the same pattern in polyacrylamide gels as did AcMNPV
      structural polypeptides. GmMNPV and TnMNPV had several minor structural protein
      differences as compared with AcMNPV. AcMNPV variants, TnMNPV, and GmMNPV were
      distinct but with very similar genomes and protein structures.

PMID- 16789180
TI  - Genetic Analysis of a Baculovirus, Autographa californica Nuclear Polyhedrosis
      Virus I. Isolation of Temperature-Sensitive Mutants and Assortment into
      Complementation Groups.
AB  - Temperature-sensitive (ts) mutants were isolated from the baculovirus Autographa
      californica (alfalfa looper) MNPV, grown in Spodoptera frugiperda (fall armyworm)
      cells in the presence of N-methyl-N'-nitro-N-nitrosoguanidine. Of 567 plaque
      isolates screened, 27 were temperature sensitive (ts), representing a mutation
      frequency of 4.8%. Ten ts mutants were studied in detail: six failed to yield
      nonoccluded virus at 33 degrees C (NOV mutants), whereas the other four produced
      nonoccluded virus but were restricted in formation of polyhedra at 33 degrees C
      (Poly mutants). One of the six NOV mutants failed to synthesize viral DNA.
      Reversion and leak frequencies were determined, and the mutants were assorted
      into complementation groups based on the yield of polyhedrin synthesis in cells
      coinfected with pairs of mutants at 33 degrees C, as measured by
      radioimmunoassay. For NOV mutants, complementation indexes were also based on
      virus yield and were consistent with those based on polyhedrin synthesis. Nine
      mutants were assorted into five complementation groups. One mutant remained
      unclassified.

PMID- 16789181
TI  - Isolation, Complementation, and Initial Characterization of Temperature-Sensitive
      Mutants of the Baculovirus Autographa californica Nuclear Polyhedrosis Virus.
AB  - Sixteen temperature-sensitive mutants of Autographa californica nuclear
      polyhedrosis virus were isolated. Several interesting phenotypes were observed. A
      large proportion of the mutants were unable to form polyhedral occlusion bodies
      (polyhedra) at the nonpermissive temperature (32.5 degrees C). At 32.5 degrees C,
      one mutant formed plaques in which the cells lacked polyhedra. Another mutant
      type was defective in the production of progeny extracellular nonoccluded virus
      and produced a "plaque" consisting of only a single cell containing polyhedra at
      32.5 degrees C. One mutant was defective in plaque formation, progeny nonoccluded
      virus formation, and polyhedra formation at 32.5 degrees C. Several mutants
      produced nonoccluded virus but failed to produce plaques or polyhedra at 32.5
      degrees C. Other phenotypes were also distinguished. Complementation analyses,
      performed by either measuring the increase in extracellular nonoccluded virus
      formation or by observing polyhedra formation in mixed infections at 32.5 degrees
      C, indicated the presence of 15 complementation groups. A high frequency of
      recombination was observed. Four of the mutants were found to be host dependent
      in their temperature sensitivity for polyhedra formation.

PMID- 16789182
TI  - Physical Map of the Channel Catfish Virus Genome: Location of Sites for
      Restriction Endonucleases EcoRI, HindIII, HpaI, and XbaI.
AB  - The overall arrangement of nucleotide sequences in the DNA of channel catfish
      virus has been studied by cleavage with four restriction endonucleases. Physical
      maps have been developed for the location of sites for EcoRI, HindIII, HpaI, and
      XbaI. The sum of the molecular weights of fragments generated by each restriction
      enzyme indicates a molecular weight of approximately 86 x 10(6) for the channel
      catfish virus genome. Fragments corresponding to the molecular ends of channel
      catfish virus DNA have been identified by their sensitivity to exonuclease
      treatment. The distribution of restriction sites in the genome shows that
      sequences included in a 12 x 10(6)-molecular weight region at one end are
      repeated with direct polarity at the other end, and that the overall genomic
      sequence order is nonpermuted.

PMID- 16789184
TI  - Virus-specific RNA synthesis in cells infected by infectious pancreatic necrosis
      virus.
AB  - Pulse-labeling experiments with [(3)H]uridine revealed that the rate of
      infections pancreatic necrosis virus-specific RNA synthesis was maximal at 8 to
      10 h after infection and was completely diminished by 12 to 14 h. Three forms of
      RNA intermediates were detected: (i) a putative transcription intermediate (TRI)
      which comigrated in acrylamide gels with virion double-stranded RNA (dsRNA) after
      RNase treatment; (ii) a 24S genome length mRNA which could be resolved into two
      bands by polyacrylamide gel electrophoresis; and (iii) a 14S dsRNA component
      indistinguishable from virion RNA by gradient centrifugation and gel
      electrophoresis. The TRI (i) was LiCl precipitable; (ii) sedimented slightly
      faster and broader (14 to 16S) than the 14S virion dsRNA; (iii) had a lower
      electrophoretic mobility in acrylamide gels than dsRNA, barely entering
      acrylamide gels as a heterogenous component; (iv) yielded genome-sized pieces of
      dsRNA after RNase digestion; and (v) was the most abundant RNA form early in the
      infectious cycle. The 24S single-stranded RNA was thought to be the viral mRNA
      since it: (i) became labeled during short pulses; (ii) was found in the polysomal
      fraction of infected cells; and (iii) hybridized to denatured viral RNA, forming
      two segments of RNase-resistant RNA that comigrated with virion dsRNA in gels.
      The 24S mRNA component was formed before the synthesis of dsRNA, and
      radioactivity could be chased from 24S single-stranded RNA to dsRNA, indicating
      that 24S RNA may serve as template for the synthesis of complementary strands to
      form dsRNA. Similar to reovirus, infectious pancreatic necrosis viral 24S mRNA
      contained no polyadenylic acid tracts.

PMID- 16789183
TI  - Characterization of cricket paralysis virus-induced polypeptides in Drosophila
      cells.
AB  - Cricket paralysis virus purified from Galleria mellonella larvae was shown to be
      similar to virus purified from Drosophila melanogaster cells. Cricket paralysis
      virus contained three major structural polypeptides of similar molecular weight
      (around 30,000), had a buoyant density of 1.344 g/ml, and had a capsid diameter
      of 27 nm. Twenty virus-induced polypeptides could be detected in CrPV-infected
      Drosophila cells. Two major polypeptides found in the infected cells corresponded
      to two structural viral polypeptides (VP1 and VP3), whereas the third major
      intracellular polypeptide was the apparent precursor of the third viral
      structural polypeptide (VP2). Three of the primary virus-induced polypeptides had
      molecular weights of 144,000, 124,000, and 115,000. These and other polypeptides
      were chased into lower-molecular-weight proteins when excess cold methionine was
      added after a short [(35)S]methionine pulse. Although cricket paralysis virus has
      a number of characteristics in common with the mammalian enteroviruses, the
      extremely fast processing of high-molecular-weight polypeptides into viral
      proteins seems atypical. Also, no VP4 (8,000 to 10,000 molecular weight) has been
      found in the virus particles.

PMID- 16789185
TI  - Frog Virus 3 Replication: Analysis of Structural and Nonstructural Polypeptides
      in Infected BHK Cells by Acidic and Basic Two-Dimensional Gel Electrophoresis.
AB  - Analysis of frog virus 3-infected BHK cells by two-dimensional, acidic and basic
      gel electrophoresis showed that at least 90 infected cell-specific polypeptides
      could be detected. These polypeptides represent between 70 and 85% of the coding
      capacity of the viral genome. The polypeptides were sequentially induced in at
      least three phases. The virus gradually suppressed host cell polypeptide
      synthesis during infection, although the synthesis of a few cell polypeptides may
      be "switched off" early in infection.

PMID- 16789186
TI  - Frog virus 3 replication: induction and intracellular distribution of
      polypeptides in infected cells.
AB  - The synthesis of the polypeptides induced in frog virus 3-infected cells was
      analyzed by high-resolution sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of radiolabeled cell extracts. Purified frog virus 3 contained 22
      polypeptides, with molecular weights in the range 9 x 10(3) to 114 x 10(3). All
      of the structural and an additional seven nonstructural polypeptides were
      detected in infected cell lysates. The following three classes of induced
      polypeptides (under temporal control) were observed in BHK cells: at 2 h, four
      alpha polypeptides; at 4 h, 13 beta polypeptides; and at 6 h, the remaining 12
      gamma polypeptides. The total molecular weight of the infected cell-specific
      polypeptides (ICPs) was approximately 1.5 x 10(6), which accounts for about 30%
      of the coding capacity of the viral genome. At least 10 of the induced
      polypeptides were phosphorylated, but none was glycosylated or sulfated. No
      evidence for posttranslation cleavage of polypeptides in pulse-chase and
      inhibition experiments was obtained. The synthesis of gamma polypeptides was not
      detected in the presence of the viral DNA replication inhibitors cytosine
      arabinoside and hydroxyurea, but halogenated nucleotides apparently had no
      effect. These results suggest that alpha and beta polypeptides are "early" events
      and that detectable gamma polypeptide synthesis is dependent on the production of
      progeny viral DNA. The regulation of frog virus 3-induced polypeptide synthesis
      in infected BHK cells was examined by using inhibitors of protein and RNA
      synthesis and amino acid analogs. These experiments confirmed the existence of
      three sequentially synthesized, coordinately regulated classes of polypeptides,
      designated alpha, beta, and gamma. The requirements for the synthesis of each
      class were as follows: (i) alpha polypeptides did not require previous cell
      protein synthesis; (ii) beta polypeptides required a prescribed period of alpha
      polypeptide synthesis and new mRNA synthesis; and (iii) gamma polypeptides
      required prior synthesis of functional beta polypeptides and new mRNA synthesis.
      alpha polypeptide synthesis was controlled by beta and gamma polypeptides, and
      alpha and beta polypeptides were involved in the suppression of host cell
      polypeptide synthesis. Indirect evidence was obtained for the temporal regulation
      of frog virus 3 transcription. The intracellular distribution of virus-induced
      polypeptides in cells infected with frog virus 3 was investigated by using
      standard cell fractionation techniques. Most of the 29 induced polypeptides were
      bound to structures within the nucleus, and only two ICPs were not associated
      with purified nuclei. When isolated nuclei were incubated in an infected cell
      cytoplasm preparation, all of the nuclear ICPs were incorporated in vitro. All of
      the ICPs were associated with ribosomal and rough endoplasmic reticulum fractions
      of infected cells, and a number of ICPs were found on smooth intracellular
      membranes. Most of the ICPs were also associated with purified plasma membranes
      of infected cells, and one polypeptide (ICP 58) was highly enriched in the plasma
      membrane compared with whole cell extracts or purified frog virus 3.

PMID- 16789188
TI  - Restriction Map of Rachiplusia ou and Rachiplusia ou-Autographa californica
      Baculovirus Recombinants.
AB  - The restriction sites of Rachiplusia ou nuclear polyhedrosis virus (RoMNPV) DNA
      were mapped for the endonucleases SmaI, KpnI, BamHI, SacI, XhoI, and EcoRI. Of
      the 60 DNA restriction sites of RoMNPV, 35 mapped in similar positions as
      compared to the restriction sites of Autographa californica nuclear polyhedrosis
      virus (AcMNPV) DNA. Two plaque-purified viruses, obtained from randomly picked
      plaques of a wild-type isolate of RoMNPV, were recombinants of RoMNPV and AcMNPV.
      The recombinants were shown to have RoMNPV and AcMNPV restriction fragments as
      well as structural polypeptides from each parental virus. Both recombinant
      viruses had a major RoMNPV capsid protein but were occluded in the AcMNPV
      polyhedrin protein.

PMID- 16789187
TI  - Alternate capping mechanisms for transcription of spring viremia of carp virus:
      evidence for independent mRNA initiation.
AB  - Two alternate mechanisms of mRNA capping for spring viremia of carp virus have
      been observed. Under normal reaction conditions, a ppG residue of the capping GTP
      is transferred to a pA moiety of the 5' termini of mRNA transcripts. However, in
      reaction conditions where GppNHp is used instead of GTP, an alternate capping
      mechanism occurs whereby a pG residue of the capping GTP is transferred to a ppA
      moiety of the transcripts. The first mechanism is identical to that described
      previously for vesicular stomatitis virus (G. Abraham, D. P. Rhodes, and A. K.
      Banerjee, Nature [London] 255:37-40, 1975; A. K. Banerjee, S. A. Moyer, and D. P.
      Rhodes, Virology 61:547-558, 1974), and thus appears to be a conserved function
      during the evolution of rhabdoviruses. The alternate mechanism of capping
      indicates not only that capping can take place by two procedures, but also that
      the substrate termini have di- or triphosphate 5' ends, indicating that they are
      probably independently initiated. An analog of ATP, AppNHp, has been found to
      completely inhibit the initiation of transcription by spring viremia of carp
      virus, suggesting that a cleavage between the beta and gamma phosphates of ATP is
      essential for the initiation of transcription. However, in the presence of
      GppNHp, uncapped (ppAp and pppAp), capped (GpppAp), and capped methylated
      (m7GpppAmpAp and GpppAmpAp) transcripts are detected. Size analyses of
      oligodeoxythymidylic acid-cellulose-bound transcripts resolved by formamide gel
      electrophoresis demonstrated that full-size mRNA transcripts are synthesized as
      well as larger RNA species. The presence of GppNHp and S-adenosylhomocysteine in
      reaction mixtures did not have any effect on the type of unmethylated
      transcription products. Our results favor a transcription model postulated
      previously (D. H. L. Bishop, in H. Fraenkel-Conrat and R. R. Wagner, ed.,
      Comprehensive Virology, vol. 10, Plenum Press, New York, 1977; D. H. L. Bishop
      and A. Flamand, in D. C. Burke and W. C. Russell, ed., Control Processes in Virus
      Multiplication, Cambridge University Press, Cambridge, 1975; D. H. L. Bishop and
      M. S. Smith, in D. Nayak, ed., The Molecular Biology of Animal Viruses, Marcel
      Dekker, New York, 1977; P. Roy and D. H. L. Bishop, J. Virol. 11:487-501, 1973)
      in which mRNA synthesis is initiated independently; they do not support a model
      for transcripts being synthesized by plus-strand cleavage (A. K. Banerjee, G.
      Abraham, and R. J. Colonno, J. Gen. Virol. 34:1-8, 1977; A. K. Banerjee, R. J.
      Colonno, D. Testa, and M. T. Franze-Fernandez, in B. M. J. Mahy and R. D. Barry,
      ed., Negative Strand Viruses and the Host Cells, Academic Press, London, 1978).

PMID- 16789189
TI  - Phosphonoacetic Acid inhibition of frog virus 3 replication.
AB  - Phosphonoacetic acid at concentrations above 200 mug/ml inhibited the replication
      of frog virus 3 in BHK cells. The inhibition of viral DNA replication observed in
      these cells was reversible and correlated with the inhibition of the virus
      induced DNA polymerase activity in an in vitro assay. The synthesis of frog virus
      3-induced late or gamma polypeptides was also inhibited by phosphonoacetic acid,
      although the early (alpha and beta) polypeptides were unaffected.

PMID- 16789190
TI  - Characterization of an extremely basic protein derived from granulosis virus
      nucleocapsids.
AB  - Nucleocapsids were isolated from purified enveloped nucleocapsids of Plodia
      interpunctella granulosis virus by treatment with Nonidet P-40. When analyzed on
      sodium dodecyl sulfate-polyacrylamide gels, the nucleocapsids consisted of eight
      polypeptides. One of these, a major component with a molecular weight of 12,500
      (VP12), was selectively extracted from the nucleocapsids with 0.25 M sulfuric
      acid. Its electrophoretic mobility on acetic acid-urea gels was intermediate to
      that of cellular histones and protamine. Amino acid analysis showed that 39% of
      the amino acid residues of VP12 were basic: 27% were arginine and 12% were
      histidine. The remaining residues consisted primarily of serine, valine, and
      isoleucine. Proteins of similar arginine content also were extracted from the
      granulosis virus of Pieris rapae and from the nuclear polyhedrosis viruses of
      Spodoptera frugiperda and Autographa californica. The basic polypeptide appeared
      to be virus specific because it was found in nucleocapsids and virus-infected
      cells but not in uninfected cells. VP12 was not present in polypeptide profiles
      of granulosis virus capsids, indicating that it was an internal or core protein
      of the nucleocapsids. Electron microscopic observations suggested that the basic
      protein was associated with the viral DNA in the form of a DNA-protein complex.

PMID- 16789191
TI  - Structural Polypeptides of the Granulosis Virus of Plodia interpunctella.
AB  - Techniques were developed for the isolation and purification of three structural
      components of Plodia interpunctella granulosis virus: granulin, enveloped
      nucleocapsids, and nucleocapsids. The polypeptide composition and distribution of
      protein in each viral component were determined by sodium dodecyl sulfate
      discontinuous and gradient polyacrylamide slab gel electrophoresis. Enveloped
      nucleocapsids consisted of 15 structural proteins ranging in molecular weight
      from 12,600 to 97,300. Five of these proteins, having approximate molecular
      weights of 17,800, 39,700, 42,400, 48,200, and 97,300, were identified as
      envelope proteins by surface radioiodination of the enveloped nucleocapsids.
      Present in purified nucleocapsids were eight polypeptides. The predominant
      proteins in this structural component had molecular weights of 12,500 and 31,000.
      Whereas no evidence of polypeptide glycosylation was obtained, six of the viral
      proteins were observed to be phosphorylated.

PMID- 16789192
TI  - Translation of southern bean mosaic virus RNA in wheat embryo and rabbit
      reticulocyte extracts.
AB  - Southern bean mosaic virus RNA was translated in wheat embryo extracts and in
      nuclease-treated rabbit reticulocyte lysates. Four principal products were
      synthesized: two related products with molecular weights of 105,000 and 75,000, a
      product with a molecular weight of 29,000 that closely resembled coat protein,
      and a product with a molecular weight of 14,000. Their proportion depended on
      ionic conditions and the translational system used.

PMID- 16789193
TI  - Post-Translational Proteolytic Cleavage of In Vitro-Synthesized Turnip Yellow
      Mosaic Virus RNA-Coded High-Molecular-Weight Proteins.
AB  - In a reticulocyte lysate, turnip yellow mosaic virus genomic RNA directs the
      synthesis of two proteins with molecular weights of 150,000 (150K) and 195K. We
      present evidence that the larger protein is processed in vitro, after its
      completion, in at least three fragments. The NH(2)-terminal fragment (82K) and
      the COOH-terminal fragment (78K) have been well characterized by different
      methods. The fact that the 150K protein is not cleaved in vitro, although it
      contains the regions that are processed in the 195K protein, could be of
      fundamental biological significance for the expression of the viral genes: a
      single polypeptide chain could be processed in several ways, leading to different
      peptides with distinct biological activities.

PMID- 16789194
TI  - Regulation of brome mosaic virus gene expression by restriction of initiation of
      protein synthesis.
AB  - The translation of total and individual brome mosaic virus (BMV) RNAs was
      examined in a wheat germ cell-free system in the presence of various inhibitors.
      Inhibitors of the initiation of polypeptide synthesis, e.g., potassium ions, 7
      methylguanosine 5' -monophosphate, and aurintricarboxylic acid, were shown not
      only to inhibit overall BMV protein synthesis but also to change the ratio of BMV
      polypeptides synthesized. Under conditions restrictive for initiation, the
      translation of nonstructural BMV genes was suppressed, but coat protein synthesis
      proceeded at a high rate. A similar discrimination among BMV messengers was
      exerted by a regulatory protein kinase isolated from wheat germ. These results
      suggest that the regulation of the expression of BMV genes is based on a
      difference in the mechanism of formation of initiation complexes for individual
      BMV messages.

PMID- 16789195
TI  - Comparison of the Structure of C- and N-Polyhedrins from Two Occluded Viruses
      Pathogenic for Orgyia pseudotsugata.
AB  - C-and N-polyhedrins from a cytoplasmic polyhedrosis virus (a double-stranded RNA
      virus) and a nuclear polyhedrosis virus (a DNA virus), respectively, of Orgyia
      pseudotsugata were compared. Although both polyhedrins appear to stabilize their
      respective virions and have similar molecular weights, they differed in amino
      acid composition, tryptic peptide elution profiles from a cation-exchange resin,
      and N-terminal amino acid sequence and showed no antigenic relatedness. This
      suggests that these two proteins originated independently of one another.

PMID- 16789196
TI  - Expression of wound tumor virus gene products in vivo and in vitro.
AB  - Infection of Agallia constricta vector cell monolayers with wound tumor virus
      results in the synthesis of 12 virus-specific polypeptides. Confirmation that
      these polypeptides are virus encoded rather than virus induced was obtained by
      cell-free translation of in vitro synthesized viral mRNA. In addition,
      transcription by purified wound tumor virus particles was coupled with
      translation of the resulting transcripts in a wheat embryo cell-free extract. Six
      previously described structural polypeptides, one presumptive structural
      polypeptide, and five previously unidentified nonstructural polypeptides were
      synthesized in infected vector cell monolayers, in cell-free extracts directed by
      in vitro synthesized viral mRNA, and in the homologous plant cell-free system, in
      which viral transcription was coupled with translation. Pulse-chase experiments
      revealed no evidence of precursor-product relationships for the wound tumor virus
      specific polypeptides.

PMID- 16789197
TI  - Genetic Analysis of Orbiviruses by Using RNase T(1) Oligonucleotide Fingerprints.
AB  - Corresponding double-stranded RNA segments of the related orbiviruses Wallal and
      Mudjinbarry produced distinctly different RNase T(1) fingerprint patterns. No
      extensive sequence reiteration was observed between segments of Mudjinbarry
      virus. Fingerprint analysis of the genome of recombinant orbiviruses confirmed
      segment reassortment as a mechanism of interchange of genetic information. When
      temperature-sensitive mutants of each virus were crossed in mixed infection, a
      consistent pattern of segment reassortment was correlated with generation of the
      wild-type phenotype. Thus, the temperature-sensitive lesion of group II Wallal
      serogroup mutants was mapped to segment 1. The group I mutant lesion appears to
      be located in segment 2.

PMID- 16789198
TI  - Physical Maps of Autographa californica and Rachiplusia ou Nuclear Polyhedrosis
      Virus Recombinants.
AB  - TN-368 cells were infected simultaneously with the closely related Autographa
      california (AcMNPV) and Rachiplusia ou (RoMNPV) nuclear polyhedrosis viruses.
      Progeny viral isolates were plaque purified, and their DNAs were analyzed with
      restriction endonucleases. Of 100 randomly cloned plaques, 7 were AcMNPV and
      RoMNPV recombinants, 5 were RoMNPV, and 88 were AcMNPV. The recombinants
      contained DNA sequences derived from both parental genomes. By comparing the
      restriction cleavage patterns of parental and recombinant DNAs, the crossover
      sites were mapped. A single double crossover was detected in each of the seven
      recombinant genomes. In addition, six of the seven recombinants revealed a
      crossover site mapping between 78 and 89% of the genome. The structural
      polypeptides of the seven recombinants and two parental viruses were analyzed by
      polyacrylamide gel electrophoresis, and their polyhedrins were identified by
      tryptic peptide mapping. An analysis of the segregation of three enveloped
      nucleocapsid proteins and of the polyhedrins among the recombinants located the
      DNA sequences coding for AcMNPV structural polypeptides with molecular weights of
      37,000 (a capsid polypeptide), 56,000, and 90,000 and the RoMNPV structural
      polypeptides with molecular weights of 36,000 (a capsid polypeptide), 56,000, and
      91,000. The AcMNPV and RoMNPV polypeptides of molecular weights 37,000 and
      36,000, respectively, mapped within 78 to 89% or 1 to 29%, the polypeptides of
      molecular weights 55,000 and 56,000 mapped within 78 to 29%, and the polypeptides
      of molecular weights 90,000 and 91,000 mapped within 19 to 56% of the genome. The
      region of the parental DNAs that codes for polyhedrin was located within 70 to
      89% of the genome.

PMID- 16789199
TI  - Enzyme activities associated with an invertebrate iridovirus: protein kinase
      activity associated with iridescent virus type 6 (chilo iridescent virus).
AB  - Iridescent virus type 6 was found to contain an endogenous protein kinase
      activity which can phosphorylate some viral proteins and exogenous basic
      proteins. The enzyme required a divalent metal ion but was not stimulated by
      cyclic nucleotides. Procedures which are known to solubilize the viral envelope
      indicated that the protein kinase was an internal component of the virion.
      Conditions for protein kinase activity are described.

PMID- 16789200
TI  - Mutations in coliphage p1 affecting host cell lysis.
AB  - A total of 103 amber mutants of coliphage P1 were tested for lysis of
      nonpermissive cells. Of these, 83 caused cell lysis at the normal lysis time and
      have defects in particle morphogenesis. Five amber mutants, with mutations in the
      same gene (gene 2), caused premature lysis and may have a defect in a lysis
      regulator. Fifteen amber mutants were unable to cause cell lysis. Artificially
      lysed cells infected with five of these mutants produced viable phage particles,
      and phage particles were seen in thin sections of unlysed, infected cells.
      However, phage production by these mutants was not continued after the normal
      lysis time. We conclude that the defect of these five mutants is in a lysis
      function. The five mutations were found to be in the same gene (designated gene
      17). The remaining 10 amber mutants, whose mutations were found to be in the same
      gene (gene 10), were also unable to cause cell lysis. They differed from those in
      gene 17 in that no viable phage particles were produced from artificially lysed
      cells, and no phage particles were seen in thin sections of unlysed, infected
      cells. We conclude that the gene 10 mutants cannot synthesize late proteins, and
      it is possible that gene 10 may code for a regulator of late gene expression for
      P1.

PMID- 16789201
TI  - Black beetle virus: propagation in Drosophila line 1 cells and an infection
      resistant subline carrying endogenous black beetle virus-related particles.
AB  - Black beetle virus (BBV), one of a recently discovered class of viruses with a
      bipartite genome, multiplied readily in Schneider's line 1 of Drosophila cells.
      Virus yields, on the order of 100 mg per liter of culture, were unusually high
      and represented some 20% of the total cell protein within 3 days after infection.
      A derivative subline of these Drosophila cells was found to be resistant to
      infection by BBV. These resistant cells were also found to carry small amounts of
      BBV-related particles, possibly a maturation-defective form of BBV.

PMID- 16789202
TI  - Densonucleosis virus structural proteins.
AB  - The protein coats of two densonucleosis viruses (types 1 and 2) were examined by
      a variety of biophysical, biochemical, and serological techniques. The viruses
      were 24 nm in diameter, contained at least four polypeptides, were remarkably
      stable to extremes of pH and denaturing agents, and were serologically closely
      related. The two viruses could, however, be distinguished serologically and by
      differences in migration of their structural polypeptides. For each virus the
      "top component" (i.e., the protein coat minus DNA, found occurring naturally in
      infections) appeared to have a composition identical to that of the coat of the
      virus and was a more stable structure. Electrometric titration curves of the
      virus particles and top components demonstrated that the DNA phosphate in
      densonucleosis virus particles was neutralized by cations other than basic amino
      acid side chains of the protein coat. Circular dichroism studies showed that
      there was a conformational difference between the protein coats of top components
      and virus particles.

PMID- 16789203
TI  - Expression of bottom component RNA of cowpea mosaic virus in cowpea protoplasts.
AB  - Upon inoculation of cowpea protoplasts with the bottom component of cowpea mosaic
      virus, at least six virus-induced proteins (with sizes of 170, 110, 87, 84, 60,
      and 32 kilodaltons) are synthesized, but not the capsid proteins (37 and 23
      kilodaltons). These bottom-component-induced proteins were studied with respect
      to their genetic origin and mode of synthesis. The analyses were based on their
      electrophoretic peptide patterns resulting from partial digestion with
      Staphylococcus aureus protease V8. Comparison of the peptide patterns of the
      virus-induced proteins with those of the cowpea mosaic virus RNA-coded
      polypeptides produced in rabbit reticulocyte lysate showed that the 170- and 32
      kilodalton polypeptides, which are the first viral products in cowpea mosaic
      virus-infected cells, were actually coded by the bottom component RNA of the
      virus. The 110-, 87-, and 84-kilodalton polypeptides, and possibly the 60
      kilodalton polypeptide, appeared to have amino acid sequences in common with the
      170-kilodalton polypeptide, demonstrating that they were virus coded as well. The
      results indicated that cowpea mosaic virus bottom component RNA was translated in
      vivo into a single 200-kilodalton polyprotein from which probably all bottom
      component-specific proteins arose by three successive cleavages.

PMID- 16789204
TI  - Dinucleotide Sequences at the 5' Ends of Vaccinia Virus mRNA's Synthesized In
      Vitro.
AB  - The diversity of dinucleotide sequences at the 5' ends of vaccinia virus mRNA's
      was determined by a two-dimensional electrophoresis procedure. RNA labeled with S
      adenosyl[methyl-(3)H]methionine was synthesized in vitro by enzymes present in
      vaccinia virus cores. The RNA, ending in m(7)G(5')pppN(m)pN-, was beta-eliminated
      and treated with alkaline phosphatase. After digestion with RNases T(2), T(1),
      and A, all eight possible dinucleotides containing G(m) and A(m) were identified.
      They are, in decreasing order of abundance: G(m)pUp (22%), A(m)pCp (18%), G(m)pAp
      (16%), G(m)pCp (15%), A(m)pAp (11%), A(m)pUp (10%), A(m)pGp (7%), and G(m)pGp
      (2%).

PMID- 16789205
TI  - Properties of cells carrying the herpes simplex virus type 2 thymidine kinase
      gene: mechanisms of reversion to a thymidine kinase-negative phenotype.
AB  - We have isolated cells with a thymidine kinase-negative (tk(-)) phenotype from
      cells which carry the herpes simplex virus type 2 tk gene by selection in 5
      bromodeoxyuridine or 9-(2-hydroxyethoxymethyl)guanine. Both selection routines
      generated revertants with a frequency of 10(-3) to 10(-4), and resistance to
      either compound conferred simultaneous resistance to the other. tk(-) revertants
      fell into three classes: (i) cells that arose by deletion of all virus sequences,
      (ii) cells that had lost the virus tk gene but retained a nonselected virus
      specific function and arose by deletion of part of the virus-specific sequence,
      and (iii) cells that retained the potential to express all of the virus-specific
      functions of the parental cells and retained all of the virus-specific DNA
      sequences.

PMID- 16789206
TI  - Isolation and Mapping of Small Cauliflower Mosaic Virus DNA Fragments Active as
      Promoters in Escherichia coli.
AB  - Small EcoRI(*) fragments of cauliflower mosiac virus DNA (strain CM4-184), which
      act as promoters for the tetracycline resistance gene on the promoter probe
      plasmid pBRH4 in Escherichia coli, have been isolated and mapped on the viral
      genome. Two regions of the viral genome contain DNA sequences with promoter
      activity in E. coli. Two independent cloned fragments from one region direct a
      high level of tetracycline resistance (up to 38 mug of tetracycline per ml). Two
      independent fragments from the second region of the viral genome also direct
      tetracycline resistance, but at lower levels. The activity of the two fragments
      with the strongest promoter activity in E. coli may direct transcription of the
      viral genome in a clockwise direction. This is consistent with the direction of
      transcription predicted from sequence analysis of the viral DNA (Franck et al.,
      Cell 21: 285-294, 1980). One of these fragments maps at the start of a large open
      translational reading frame which is predicted to contain the coding sequence for
      the viral coat protein. Each promoter-active fragment is located in the 5'
      terminal portion of one of the six open reading frames predicted from the DNA
      sequence.

PMID- 16789207
TI  - Synthesis of Black Beetle Virus Proteins in Cultured Drosophila Cells:
      Differential Expression of RNAs 1 and 2.
AB  - Black beetle virus is an insect virus with a split genome consisting of two
      single-stranded, messenger-active RNA molecules with molecular weights of 1.0 x
      10(6) (RNA 1) and 0.5 x 10(6) (RNA 2), respectively. Virions contained two
      proteins, beta with a molecular weight of 43,000 (43K) and gamma (5K), and traces
      of a third protein, alpha (47K). When translated in cell-free extracts of rabbit
      reticulocytes, RNA 1 directed the synthesis of protein A (104K), whereas RNA 2
      synthesized protein alpha. The in vitro translation efficiency of the two RNAs
      was roughly equal. Infection of cultured Drosophila cells induced the synthesis
      of five new proteins: A, alpha, beta, gamma, and B (10K), detected by
      autoradiography of polyacrylamide gels after electrophoresis of extracts from
      [(35)S]methionine-labeled cultures. All but protein gamma could also be detected
      by staining with Coomassie brilliant blue, indicating vigorous synthesis of viral
      proteins. Pulse-chase experiments in infected cells revealed the disappearance of
      protein alpha and the coordinate appearance of proteins beta and gamma,
      supporting an earlier proposal that coat protein of mature virions is made by
      cleavage of precursor alpha. Proteins A and B were stable in such pulse-chase
      experiments. The three classes of virus-induced proteins, represented by A, B,
      and alpha, were synthesized in markedly different amounts and with different
      kinetics. Synthesis of proteins A and B peaked early in infection and then
      declined, whereas synthesis of coat protein precursor alpha peaked much later.
      These results suggest that RNA 1 controls early replication functions via protein
      A (and also possibly protein B), whereas RNA 2 controls synthesis of coat protein
      required later for virion assembly.

PMID- 16789208
TI  - alpha-Amanitin-Resistant Viral RNA Synthesis in Nuclei Isolated from Nuclear
      Polyhedrosis Virus-Infected Heliothis zea Larvae and Spodoptera frugiperda Cells.
AB  - [(3)H]RNA was synthesized in nuclei isolated at various times postinfection from
      the fat bodies of Heliothis zea larvae infected with H. zea nuclear polyhedrosis
      virus and from cultured Spodoptera frugiperda cells infected with Autographa
      californica nuclear polyhedrosis virus. To detect virus-specific RNA synthesis,
      the [(3)H]RNA was hybridized to denatured viral DNA immobilized on nitrocellulose
      filters. Nuclear polyhedrosis virus-specific RNA synthesis in the infected nuclei
      isolated from H. zea larval fat bodies and S. frugiperda cells was only inhibited
      20 to 25% by concentrations of alpha-amanitin sufficient to inhibit the host RNA
      polymerase II. In addition, a productive nuclear polyhedrosis virus infection was
      obtained in S. frugiperda cells grown in the presence of an alpha-amanitin
      concentration that inhibited 90% of the cellular RNA polymerase II activity. The
      cellular RNA polymerase II enzyme remained sensitive to alpha-amanitin during
      infection, and there was no evidence that a virus-coded, alpha-amanitin-resistant
      enzyme was synthesized after the onset of infection. The data suggest that the
      bulk of nuclear polyhedrosis virus-specific RNA synthesis in isolated nuclei is
      transcribed by an enzyme other than the host RNA polymerase II.

PMID- 16789209
TI  - Spodoptera frugiperda Nuclear Polyhedrosis Virus Genome: Physical Maps for
      Restriction Endonucleases BamHI and HindIII.
AB  - The physical map for the genome of Spodoptera frugiperda nuclear polyhedrosis
      virus was constructed for restriction endonucleases BamHI and HindIII. The
      ordering of the restriction fragments was accomplished by cross-blot
      hybridization of BamHI, HindIII, and EcoRI fragments. The alignment of the
      HindIII fragments within the BamHI map was achieved by double digestion with the
      two restriction endonucleases followed by cross-blot hybridization. The results
      showed that the viral genome consisted of mainly unique sequences. In addition,
      the circular nature of the viral genome was reaffirmed.

PMID- 16789210
TI  - Application of a novel radioimmunoassay to identify baculovirus structural
      proteins that share interspecies antigenic determinants.
AB  - Immunological comparisons were made of baculovirus structural proteins by using a
      modification of the radioimmunological techniques described by Renart et al.
      (Proc. Natl. Acad. Sci. U.S.A. 76: 3116-3120, 1979) and Towbin et al. (Proc.
      Natl. Acad. Sci. U.S.A. 76: 4350-4354, 1979). Viral proteins were electrophoresed
      in polyacrylamide gels, transferred to nitrocellulose, and incubated with viral
      antisera, and the antibodies were detected with (125)I-labeled Staphylococcus
      aureus protein A. Antisera were prepared to purified and intact virions from five
      baculoviruses: Autographa californica, Porthetria dispar, Trichoplusia ni, and
      Heliothis zea nuclear polyhedrosis viruses (NPVs) and T. ni granulosis virus
      (GV). These antisera were tested against the virion structural polypeptides of 17
      different species of baculoviruses. Specific multiple-nucleocapsid NPV (MNPV),
      single-nucleocapsid NPV (SNPV), and GV virion polypeptides were shown to have
      similar antigenic determinants and thus be immunologically related. The molecular
      weights of the virion polypeptides with cross-reacting antigenic determinants
      were identified. Antisera prepared to purified A. californica and H. zea MNPV
      polyhedrin (the occlusion body protein from NPVs) recognized antigenic
      determinants on all the polyhedrins and granulins (occlusion body protein from
      GVs) that were tested. No immunological relationship was detected between A.
      californica MNPV polyhedrin and any of the A. californica MNPV virion structural
      polypeptides present on either the virus isolated from occlusion bodies or A.
      californica MNPV extracellular virus from infected-cell cultures.

PMID- 16789211
TI  - Characterization of the coat protein mRNA of southern bean mosaic virus and its
      relationship to the genomic RNA.
AB  - RNA isolated from southern bean mosaic virions contains, in small amount, a
      subgenomic RNA (molecular weight, 0.38 x 10(6)) that serves in vitro as an mRNA
      for southern bean mosaic virus coat protein. The RNA has a 5'-linked protein
      indistinguishable from the protein linked to the 5' end of full-length genomic
      RNA. Its base sequence, determined to 91 bases from the 3' end, is identical to
      the 3'-terminal sequence of the genomic RNA. The results suggest that the coat
      protein messenger sequence exists as a "silent" cistron near the 3' end of the
      genomic RNA.

PMID- 16789212
TI  - In vitro synthesis and modification of mRNA by exvectorial isolates of wound
      tumor virus.
AB  - Nontransmissible (exvectorial) isolates of wound tumor virus retain the ability
      to catalyze in vitro synthesis of RNA. Furthermore, exvectorial virus particles
      exhibit mRNA-2'-O-methyltransferase activity even after long-term (30-year)
      passage in a host that lacks this enzyme activity.

PMID- 16789213
TI  - Construction of a Genetic Map of the Baculovirus Autographa californica Nuclear
      Polyhedrosis Virus by Marker Rescue of Temperature-Sensitive Mutants.
AB  - Mutations of seven temperature-sensitive mutants of the baculovirus Autographa
      californica nuclear polyhedrosis virus (NPV) were mapped with respect to the
      physical restriction map of the A. californica NPV DNA by marker rescue. DNAs
      from two distantly related NPVs of the multiply embedded type and two NPVs of the
      singly embedded type were unable to rescue two A. californica NPV mutants.

PMID- 16789214
TI  - Isolation and Characterization of an RNA-Dependent RNA Polymerase from Black
      Beetle Virus-Infected Drosophila melanogaster Cells.
AB  - Crude lysates of black beetle virus (BBV)-infected cells of Drosophila
      melanogaster contain an RNA-dependent RNA polymerase activity not detectable in
      uninfected cells. The activity (designated BBV polymerase) sedimented at 20,000 x
      g, indicating an association with particulate material. It was solubilized from
      the pellet by sonication in a magnesium-deficient buffer. Differential
      centrifugation resulted in a 43-fold purification with 84% recovery of polymerase
      activity. The effects of divalent and monovalent cations, time, temperature, and
      pH on the activity of the partially purified polymerase were examined. RNA
      synthesis was not stimulated by the addition of exogenous BBV RNA, suggesting
      that an enzyme-template complex existed. Analysis of the RNA products of the RNA
      polymerase reaction indicated that full-length "negative" strand BBV RNAs were
      synthesized.

PMID- 16789215
TI  - Hybridization Selection and In Vitro Translation of Autographa californica
      Nuclear Polyhedrosis Virus mRNA.
AB  - We isolated polyadenylated RNA from the cytoplasm of cells infected with
      Autographa californica nuclear polyhedrosis virus late after infection (21 h
      postinfection). At that time intracellular protein synthesis was directed almost
      exclusively toward infected cell-specific proteins. The polyadenylic acid
      containing RNA sequences in the cytoplasm at 21 h postinfection were radiolabeled
      in vitro and hybridized to A. californica nuclear polyhedrosis virus DNA
      restriction fragments. The polyadenylic acid-containing RNA was derived from
      regions representing the entire viral genome. Translation in a reticulocyte cell
      free protein-synthesizing system of cytoplasmic RNA selected by hybridization to
      viral DNA and polyadenylic acid-containing RNA produced almost identical
      polypeptide patterns, suggesting that late after infection almost all of the
      cytoplasmic polyadenylic acid-containing RNA present in infected cells was of
      viral origin. Polyhedrin protein (molecular weight, 33,000) and a number of
      virion structural proteins were among the translation products which were
      identified by immunoprecipitation and by comparing molecular weights. In
      addition, some tentative nonstructural infected cell-specific proteins were also
      detected. Using the hybridization selection technique, we determined that
      sequences complementary to the message coding for polyhedrin were located on
      EcoRI fragment I of A. californica nuclear polyhedrosis virus DNA, whereas
      sequences coding for a putative nonstructural protein (molecular weight, 39,000)
      were on EcoRI fragment J.

PMID- 16789216
TI  - Expression of Middle-Component RNA of Cowpea Mosaic Virus: In Vitro Generation of
      a Precursor to Both Capsid Proteins by a Bottom-Component RNA-Encoded Protease
      from Infected Cells.
AB  - The expression of the middle-component (M) RNA of cowpea mosaic virus was studied
      by means of in vitro translation. In both the wheat germ extract and the rabbit
      reticulocyte lysate, M RNA was translated into two overlapping polypeptides of 95
      and 105 kilodaltons. Incubation of these polypeptides with 30,000 x g supernatant
      fractions from cowpea mesophyll protoplasts inoculated with complete virus or
      with separate bottom (B) components alone resulted in extensive processing,
      yielding polypeptides of 60, 58, 48, and 47 kilodaltons. Similar proteolytic
      activity was found associated with the in vitro translation products from the
      bottom-component RNA, demonstrating that the protease present in infected cells
      is encoded by B RNA. Using antisera raised against the separate capsid proteins
      VP23 and VP37, it was shown that the 60-kilodalton cleavage product is the
      precursor to both capsid proteins. Cleavage of nascent 95- and 105- kilodalton
      polypeptides by the in vivo protease demonstrated that this capsid protein
      precursor is located C terminally within both polypeptides and that the synthesis
      of these two overlapping polypeptides is the result of two initiation sites on
      middle-component RNA. In addition, a second virus-induced proteolytic activity,
      capable of releasing VP23 from the 95- and 105-kilodalton polypeptides, was
      detected in leaves of infected plants, but not in infected mesophyll protoplasts.
      A model for the expression of the middle-component RNA is presented.

PMID- 16789217
TI  - Antibodies Against the Genome-Linked Protein VPg of Cowpea Mosaic Virus Recognize
      a 60,000-Dalton Precursor Polypeptide.
AB  - We have prepared a rabbit antiserum specifically directed against the genome
      linked protein (VPg) of cowpea mosaic virus by injecting an hydrolysate of
      purified virion RNA. Using this antiserum as a probe in combination with
      "Western" (protein) blots of subcellular fractions of cowpea mosaic virus
      infected cowpea (Vigna unguiculata) cells, we have detected a bottom component
      RNA-encoded, 60,000-dalton polypeptide which is membrane bound and presumably
      represents the immediate precursor of VPg.

PMID- 16789218
TI  - Orientation of the Genome of Autographa californica Nuclear Polyhedrosis Virus: a
      Proposal.
AB  - The nuclear polyhedrosis virus of the alfalfa looper Autographa californica
      contains a double-stranded, circular DNA genome. Fourteen scientists agreed to
      accept an orientation of this circular genome with respect to a physical map of
      the restriction endonuclease cleavage sites.

PMID- 16789219
TI  - Molecular Cloning and Physical Mapping of Restriction Endonuclease Fragments of
      Autographa californica Nuclear Polyhedrosis Virus DNA.
AB  - A restriction fragment library containing Autographa californica nuclear
      polyhedrosis virus (AcNPV) DNA was constructed by using the pBR322 plasmid as a
      vector. The library, which is representative of more than 95% of the viral
      genome, consists of 2 of the 7 BamHI fragments, 12 of the 24 HindIII fragments,
      and 23 of the 24 EcoRI fragments. The cloned fragments were characterized and
      used to generate physical maps of the genome by hybridizing nick-translated
      recombinant plasmid to Southern blots of AcNPV DNA digested with SmaI, BamHI,
      XhoI, PstI, HindIII, and EcoRI restriction endonucleases. This information was
      used to define our strain of AcNPV (HR3) with respect to other strains for which
      physical maps have been previously published. The hybridization data also
      indicate that reiteration of DNA sequences occurs at the HindIII-L and -Q regions
      of the genome.

PMID- 16789220
TI  - Correlation of the Genetic Map and the Endonuclease Site Map of Bacillus subtilis
      Bacteriophage SP02.
AB  - By marker rescue of bacteriophage SP02 sus mutants with purified bacteriophage
      SP02 DNA fragments, 11 of the 17 known bacteriophage SP02 sus loci were assigned
      to discrete DNA fragments. The left-most genetic locus, susA, was found to reside
      near one bacteriophage SP02 terminus (EcoRI-C1 fragment), whereas the right-most
      genetic locus, susP, was found to reside near the other bacteriophage SP02
      terminus (EcoRI-C2 fragment). The physical locations of the intervening genetic
      loci were found to be consistent with the previously determined genetic order.
      Evidence was also obtained which suggested that at least one end of a
      transforming DNA fragment is degraded during DNA uptake by the competent
      bacterium.

PMID- 16789221
TI  - Psi, a Temperate Phage of Agrobacterium tumefaciens, Is Mutagenic.
AB  - A new temperate bacteriophage (phage Psi) of Agrobacterium tumefaciens strain B91
      is described. Many octopine-utilizing strains of A. tumefaciens harbor prophage
      Psi or a phage that is similar if not identical to it. This phage has a very
      narrow host range, and we found that its growth is strongly reduced in strains
      which carry an octopine pTi plasmid. When sensitive bacteria are infected with
      Psi, 1 to 3% of the survivors carry mutations on the chromosome, as well as on
      the pTi plasmid. This phenomenon appears to be a direct consequence of
      lysogenization. The possible mechanisms whereby such Psi-induced mutations occur
      are discussed.

PMID- 16789222
TI  - Genome of Bacillus subtilis Bacteriophage SPP1: Structure and Nucleotide Sequence
      of pac, the Origin of DNA Packaging.
AB  - The DNA of Bacillus subtilis bacteriophage SPP1 is terminally redundant and
      partially circularly permuted. To explain these parameters, we followed the
      Streisinger-Botstein models of phage maturation and assumed that packaging of
      SPP1 DNA begins at a unique genomic site ("pac") and proceeds sequentially from
      there. We describe the sequence of about 1,000 nucleotides surrounding pac. This
      together with size determinations of small, pac-terminated restriction fragments
      has revealed heterogeneity of the natural pac ends of SPP1 DNA. Such ends fell in
      each DNA strand into a region of five to seven nucleotides. However, within this
      range more than 50% of all molecules terminated with defined cytosines on both
      strands, generating a 3' protruding terminus. The nucleotide sequence of the DNA
      segment surrounding pac did not reveal any features which would distinguish this
      region.

PMID- 16789223
TI  - Expression of the Bottom-Component RNA of Cowpea Mosaic Virus: Evidence that the
      60-Kilodalton VPg Precursor Is Cleaved into Single VPg and a 58-Kilodalton
      Polypeptide.
AB  - In cowpea protoplasts infected with cowpea mosaic virus, a bottom-component (B)
      RNA-encoded 60-kilodalton (60K) polypeptide is synthesized, which is membrane
      bound and represents the direct precursor to the genome-bound protein VPg. The
      relationship between this VPg precursor and other B-RNA-encoded polypeptides was
      studied. Digestion of the B-RNA-encoded 170K and 84K polypeptides with
      Staphylococcus aureus protease V8 and subsequent analysis of the generated
      peptides with antiserum against VPg showed that a VPg sequence resides internally
      in these polypeptides. Furthermore, a new B-RNA-encoded polypeptide was detected,
      with a size of 58K, which differed from the 60K polypeptide only in the lack of
      VPg sequences. A model is presented in which the 60K VPg precursor is generated
      from the 200K primary translation product from B RNA and further processed to a
      58K polypeptide and single VPg.

PMID- 16789224
TI  - DNA Synthesis and Gene Expression in Bacillus subtilis Infected with Wild-Type
      and Hypermodification-Defective Bacteriophage SP10.
AB  - A hypermodified base (Y-Thy) replaces 20% of the thymine (Thy) in mature DNA of
      Bacillus subtilis phage SP10. Two noncomplementing hypermodification-defective
      (hmd) mutants are described. At 30 degrees C, hmd phage carried out a normal
      program, but at temperatures of >/=37 degrees C, the infection process was
      nonproductive. When cells were infected at 37 degrees C with hmd phage, DNA
      synthesis started at its usual time (12 min), proceeded at about half the normal
      rate for 6 to 8 min, and then stopped or declined manyfold. All, or nearly all,
      of the DNA made under hmd conditions consisted of fully hypermodified parental
      DNA strands H-bonded to unhypermodified nascent strands. The reduced levels of
      DNA synthesis observed under hmd conditions were accompanied by weak expression
      of late genes. A sucrose gradient analysis of SP10 hmd(+) replicating DNA
      intermediates was made. Two intermediates, called VG and F, were identified. VF
      consisted of condensed DNA complexed to protein; VF also contained negatively
      supercoiled domains covalently joined to relaxed regions. F was composed of
      linear concatenates from which mature DNA was cleaved. None of those
      intermediates was evident in cells infected at 37 degrees C with hmd phage.
      Shiftup experiments were performed wherein cells infected with hmd phage at 30
      degrees C were shifted to 37 degrees C at a time when replication was well under
      way. DNA synthesis stopped or declined manyfold 10 min after shiftup. The hmd DNA
      made after shiftup was conserved as a form sedimentationally equivalent to the F
      intermediate, but little mature DNA was evident. It is proposed that Y-Thy is
      required for replication and DNA maturation because certain key proteins involved
      with these processes interact preferentially with hypermodified DNA.

PMID- 16789225
TI  - Black beetle virus: messenger for protein B is a subgenomic viral RNA.
AB  - Black beetle virus induces the synthesis of three new proteins, protein A
      (molecular weight, 104,000), protein alpha (molecular weight, 47,000), and
      protein B (molecular weight, 10,000), in infected Drosophila cells. Two of these
      proteins, A and alpha, are known to be encoded by black beetle virus RNAs 1 and
      2, respectively, extracted from virions. We found that RNA extracted from
      infected cells directed the synthesis of all three proteins when it was added to
      a cell-free protein-synthesizing system. When polysomal RNA was fractionated on a
      sucrose density gradient, the messengers for proteins A and alpha cosedimented
      with viral RNAs 1 (22S) and 2 (15S), respectively. However, the messenger for
      protein B was a 9S RNA (RNA 3) not found in purified virions. Like the synthesis
      of viral RNAs 1 and 2, intracellular synthesis of RNA 3 was not affected by the
      drug actinomycin D at concentrations which blocked synthesis of host cell RNA.
      This indicated that RNA 3 is a virus-specific subgenomic RNA and, therefore, that
      protein B is a virus-encoded protein.

PMID- 16789226
TI  - Characterization of the DNA of a Nonoccluded Baculovirus, Hz-1V.
AB  - The DNA of the nonoccluded baculovirus (Hz-1V) obtained from the IMC-Hz-1 cell
      line was characterized by physicochemical and restriction endonuclease
      techniques. Hz-1V DNA isolated from purified virus had buoyant densities of 1.58
      and 1.54 g/ml in CsCl-ethidium bromide density gradients, which corresponded to
      supercoiled and to relaxed circular and linear DNA, respectively. Neutral CsCl
      equilibrium centrifugation indicated that the Hz-1V DNA had a buoyant density of
      1.7024 g/ml, which corresponded to a guanine-plus-cytosine (G+C) content of 43%.
      Thermal denaturation indicated a high G+C domain(s) in the Hz-1V genomic DNA. The
      domain(s), which included about 11% of the total genomic DNA, exhibited a T(m) of
      97 degrees C. The remaining portion (89%) of the DNA had a T(m) of 86.5 degrees
      C. The T(m)s corresponded to G+C contents of 42 and 67%, respectively. The mean
      genetic complexity of Hz-1V DNA determined by DNA reassociation kinetic analysis
      was found to be 152 x 10(6). A possible rapidly reassociating component
      comprising approximately 13% of the genome was observed. The mean molecular
      weights from restriction endonuclease digests were 159 x 10(6) for both HindIII
      and EcoRI. Genomic heterogeneity was found in both the wild-type Hz-1V stock and
      in two plaque isolates. Of 12 single-plaque isolates, 3 basic restriction
      endonuclease DNA fragment patterns were observed. The molecular size estimates
      from electron microscopic contour lengths of uncloned viral DNA ranged from 70 to
      158 megadaltons, and the mode was the 130- to 140-megadalton class.

PMID- 16789227
TI  - Capping of Viral RNA in Cultured Spodoptera frugiperda Cells Infected with
      Autographa californica Nuclear Polyhedrosis Virus.
AB  - Viral RNA from fall armyworm (Spodoptera frugiperda) cells infected with
      Autographa californica nuclear polyhedrosis virus contains cap structures. Most
      of the cap labeled in vivo with [(3)H]methionine or (32)P(i) cochromatographed on
      DEAE-cellulose with the -5 charge marker; a minor component appeared at -4 net
      charge. The former is probably a cap 1 structure (m(7)GpppX(m) (p)Yp), and the
      latter is probably a cap 0 (m(7)GpppXp). On the basis of relative labeling of the
      two caps with [(3)H]adenosine and [(3)H]guanosine, we concluded that each cap
      contained at least one adenosine residue in addition to guanosine and, therefore,
      that cap 0 contained m(7)GpppAp. Cleavage of [(3)H]methionine-labeled viral RNA
      with tobacco acid pyrophosphatase released a labeled component that
      cochromatographed on polyethyleneimine-cellulose with m(7)Gp, confirming the
      m(7)GpppX linkage in the cap. These results were also seen with host
      polyadenylated RNA. The caps appeared in nearly equal abundance in viral
      polyadenylated and non-polyadenylated RNAs. The ratio of (32)P(i) incorporated
      into the cap to that incorporated into mononucleotides suggested average lengths
      for the polyadenylated and non-polyadenylated RNAs of 1,800 and 1,200
      nucleotides, respectively.

PMID- 16789228
TI  - Cowpea Mosaic Virus-Encoded Protease Does Not Recognize Primary Translation
      Products of M RNAs from Other Comoviruses.
AB  - The protease encoded by the large (B) RNA segment of cowpea mosaic virus was
      tested for its ability to recognize the in vitro translation products of the
      small (M) RNA segment from the comoviruses squash mosaic virus, red clover mottle
      virus, and cowpea severe mosaic virus (CPsMV, strains Dg and Ark), and from the
      nepovirus tomato black ring virus. Like M RNA from cowpea mosaic virus, the M
      RNAs from squash mosaic virus, red clover mottle virus, CPsMV-Dg, and CPsMV-Ark
      were all translated into two large polypeptides with apparent molecular weights
      which were different for each virus and even for the two CPsMV strains. Neither
      the in vitro products from squash mosaic virus, red clover mottle virus, and
      CPsMV M RNAs nor the in vitro product from tomato black ring virus RNA-2 were
      processed by the cowpea mosaic virus-encoded protease, indicating that the
      activity of this enzyme is highly specific.

PMID- 16789229
TI  - Mapping the Mutation Site of an Autographa californica Nuclear Polyhedrosis Virus
      Polyhedron Morphology Mutant.
AB  - A polyhedron morphology mutant of Autographa californica nuclear polyhedrosis
      virus, designated M5, was compared with wild-type virus by genotypic analysis
      with EcoRI, BamHI, HindIII, SstI, and SmaI restriction endonucleases. M5 DNA
      revealed several alterations relative to the wild-type pattern: (i) EcoRI
      fragment I was 400 base pairs larger; (ii) BamHI fragment F was missing; (iii)
      HindIII fragment F was 400 base pairs larger; (iv) an extra restriction fragment
      was obtained with both HindIII and SmaI; and (v) SstI fragment G was 400 base
      pairs larger. M5 virions contained two size classes of circular DNA, one of 100%
      of the wild type and one of about 58% of the wild-type molecule. A revertant of
      M5, designated M5R, was isolated on the basis of polyhedron morphology. The
      genome of M5R contained the insertion of DNA in EcoRI fragment I and in HindIII
      fragment F, but was similar to the wild type in its other restriction fragment
      patterns. M5-infected cell cultures synthesized a polyhedrin polypeptide smaller
      in size than the wild type or M5R.

PMID- 16789230
TI  - Virus with a Multipartite Superhelical DNA Genome from the Ichneumonid Parasitoid
      Campoletis sonorensis.
AB  - Virus was isolated from the lumen of the calyx region of ovaries in the
      parasitoid wasp Campoletis sonorensis (Hymenoptera: Ichneumonidae), and the
      nature of the viral DNA was analyzed. DNA purified from a homogeneous band of
      virus contained double-stranded superhelical molecules which were polydisperse in
      molecular weight. At least 25 different covalently closed circles were present,
      ranging in molecular weight from 4.0 x 10(6) to 13.6 x 10(6). The virus DNA was
      analyzed with restriction enzymes, and the nature of the genetic complexity was
      evaluated by Southern blot hybridization of native superhelical and relaxed
      circular virus DNA and of SalI- and HindIII-digested DNA. The data suggest that
      most of the variously sized covalently closed DNAs were composed primarily of
      nonhomologous sequences. The different size classes of covalently closed viral
      DNAs did not appear to exist in equimolar concentrations. However, there was no
      evidence from observation of virus particles in the electron microscope or from
      virus fractionation experiments that a mixture of viruses was present in the
      calyx fluid. The results from this study suggest' that the virus isolated from C.
      sonorensis, like those isolated from other endoparasitic hymenoptera, may belong
      to a new class of DNA viruses in which the genome is multipartite, with each DNA
      existing as a superhelical molecule.

PMID- 16789231
TI  - In Vitro Translation of Autographa californica Nuclear Polyhedrosis Virus Early
      and Late mRNAs.
AB  - A preliminary translational map of the Autographa californica genome was
      constructed. Eighteen viral DNA restriction fragments were either purified from
      agarose gels or obtained from pBR322 recombinant DNA plasmids to locate specific
      gene products. The DNAs were immobilized on nitrocellulose filters and used to
      select viral mRNAs isolated from RNA obtained from the cytoplasm of infected
      Spodoptera frugiperda cells at 21 h postinfection. The fragment-specific mRNAs
      were translated in vitro in the presence of l-[(3)H]leucine by using a rabbit
      reticulocyte lysate system and analyzed on sodium dodecyl sulfate-polyacrylamide
      gels. The approximate locations of 19 A. californica nuclear polyhedrosis virus
      (AcMNPV) gene products were mapped. The genes for mRNAs present late in viral
      infection were mapped to DNA fragments that represent nearly the entire genome.
      The molecular weights of many of these proteins were similar to those present in
      purified AcMNPV extracellular virus and to proteins being made in infected cells
      at 18 to 21 h postinfection. Cytoplasmic RNA was isolated at 4 h postinfection
      from infected cells, a time early in the viral infection cycle, and hybridized to
      AcMNPV DNA immobilized on nitrocellulose filters. AcMNPV-specific early RNA was
      translated in vitro into at least six polypeptides, the most abundant having a
      molecular weight of 39,000. Viral polypeptides were detected in cells pulse
      labeled with l-[(3)H]leucine at 3 to 6 h postinfection, with molecular weights
      similar to those of polypeptides made in vitro from early AcMNPV mRNA.

PMID- 16789232
TI  - Homologous Terminal Sequences in the Double-Stranded RNA Genome Segments of
      Cytoplasmic Polyhedrosis Virus of the Silkworm Bombyx mori.
AB  - The 3'-terminal regions (20 to 32 residues) of the genome double-stranded RNA
      (dsRNA) segments of cytoplasmic polyhedrosis virus were sequenced. The dsRNAs,
      which were labeled at their 3' termini by incubation with [5'-(32)P]pCp and T4
      RNA ligase, were denatured and resolved into the plus and minus strands by
      agarose-urea gel electrophoresis. Ten single-stranded RNAs thus obtained from the
      five dsRNA segments IV, V, VIII, IX, and X were sequenced by postlabeling
      methods. Common 3'-terminal sequences, -GUUAGCC and -UUACU, were found in the
      plus and minus strands, respectively, of all five dsRNA segments. However,
      adjacent sequences diverged and were considerably variable. The homologous
      sequences found in the 3' end may be important recognition signals for viral RNA
      polymerases and for assembly of the genome segments.

PMID- 16789233
TI  - Analysis of the Spodoptera frugiperda Nuclear Polyhedrosis Virus Genome by
      Restriction Endonucleases and Electron Microscopy.
AB  - Restriction endonuclease analysis was used to differentiate between four strains
      of Spodoptera frugiperda nuclear polyhedrosis virus from different geographical
      areas. In addition, partial denaturation was performed, and a partial
      denaturation map was constructed for the Ohio strain of this virus.

PMID- 16789234
TI  - Two unique RNA species of the nodavirus black beetle virus.
AB  - Two-dimensional fingerprinting of RNase T(1)-derived oligonucleotides of the two
      individual RNA segments of the Nodavirus black beetle virus indicates that each
      RNA species possesses a distinct nucleotide sequence. Species 1 RNA has a genome
      complexity of approximately 3,000 nucleotides, and species 2 RNA is composed of
      approximately 1,500 nucleotides. Submolar amounts of oligonucleotides apparently
      derived from a third virus-specific RNA were also detected in black beetle virus
      RNA preparations.

PMID- 16789235
TI  - Physical Analysis of Autographa californica Nuclear Polyhedrosis Virus
      Transcripts for Polyhedrin and 10,000-Molecular-Weight Protein.
AB  - In Autographa californica nuclear polyhedrosis virus-infected cells, polyhedrin,
      the major structural polypeptide of the viral occlusions, and a low-molecular
      weight viral protein with a molecular weight of approximately 10,000 (10K)
      accumulated to high levels late in infection. Two polyadenylated RNAs 1,200 and
      630 bases in size were the most abundant viral transcripts present in the
      cytoplasm at 48 h postinfection. Evidence is presented that these RNAs were the
      transcripts for polyhedrin and 10K proteins. The 630-base RNA and five other
      major polyadenylated RNAs present at 48 h postinfection mapped within or near A.
      californica nuclear polyhedrosis virus EcoRI-P. The DNA sequences that code for
      polyhedrin mRNA were examined by S1 nuclease analysis. The polyhedrin gene
      contained no detectable introns and mapped at 3,990 to 5,200 base pairs to the
      right of the origin of the circular A. californica nuclear polyhedrosis virus
      physical map. Heterogeneity at the 5' end of polyhedrin mRNA was observed by
      using S1 nuclease analysis with 5' end-labeled DNA probes.

PMID- 16789236
TI  - Defective Interference in the Killer System of Saccharomyces cerevisiae.
AB  - The K(1) killer virus (or plasmid) of Saccharomyces cerevisiae is a noninfectious
      double-stranded RNA genome found intracellularly packaged in an icosahedral
      capsid. This genome codes for a protein toxin and for resistance to that toxin.
      Defective interfering virus mutants are deletion derivatives of the killer virus
      double-stranded RNA genome; such mutants are called suppressive. Unlike strains
      carrying the wild-type genome, strains with these deletion derivatives are
      neither toxin producers nor toxin resistant. If both the suppressive and the
      wildtype virus are introduced into the same cell, most progeny become toxin
      sensitive nonkillers (J. M. Somers, Genetics 74:571-579, 1973). Diploids formed
      by the mating of a killer with a suppressive strain were grown in liquid culture,
      and RNA was extracted from samples taken up to 41 generations after the mating.
      The ratio of killer RNA to suppressive RNA decreased with increasing generations;
      by 41 generations the killer RNA was barely detectable. The copy numbers of the
      suppressive genome and its parental killer were virtually the same in isogenic
      strains, as were the growth rates of diploid strains containing either virus
      alone. Therefore, suppressiveness, not being due to segregation or overgrowth by
      faster growing segregants, is likely due to preferential replication or
      maintenance of the suppressive genome. Three suppressive viruses, all derivatives
      of the same killer virus (T. K. Sweeney et al., Genetics 84:27-42, 1976), did not
      coexist stably. The evidence strongly indicates that the largest genome of the
      three slowly suppressed both of the smaller genomes, showing that larger genomes
      can suppress smaller ones and that suppression can occur between two
      suppressives. Of 48 isolates of strains carrying the suppressive viruses, 5 had
      newly detectable RNA species, all larger than the original suppressive genomes.
      At least seven genes necessary for maintenance of the wild-type killer virus (MAK
      genes) were needed by a suppressive mutant. No effect of ski mutations (affecting
      regulation of killer virus double-stranded RNA replication) on suppressiveness
      was observed.

PMID- 16789237
TI  - Location of Homologous DNA Sequences Interspersed at Five Regions in the
      Baculovirus AcMNPV Genome.
AB  - An examination of Autographa californica nuclear polyhedrosis virus DNA revealed
      the presence of five interspersed regions, rich in EcoRI restriction sites, which
      shared homologous sequences. These homologous regions (hr), designated hr(1) to
      hr(5), occur at or near the following EcoRI fragment junctions: hr(1)EcoRI-B
      EcoRI-I (0.0 map units); hr(2), EcoRI-A-EcoRI-J (19.8 map units); hr(3), EcoRI-C
      EcoRI-G (52.9 map units); hr(4), EcoRI-Q-EcoRI-L (69.8 map units); and hr(5),
      EcoRI-S-EcoRI-X (88.0 map units). Four of these regions were identified, by cross
      blot hybridization of HindIII-restricted A. californica nuclear polyhedrosis
      virus DNA, to be within the HindIII-A/B, -F, -L, and -Q fragments. The location
      of these regions and the identification of a fifth homologous region were
      confirmed, and their characterization was facilitated, by using two plasmids with
      HindIII-L or -Q fragment insertions, which contained the homologous regions hr(2)
      and hr(5), respectively. The sizes of the homologous regions were about 800 base
      pairs for hr(2), 500 base pairs for hr(5), and less than 500 base pairs for
      hr(1), hr(3), and hr(4). A set of small EcoRI fragments (EcoRI minifragments)
      which ranged in size from 225 to 73 base pairs were detected in A. californica
      nuclear polyhedrosis virus DNA and HindIII-L and -Q fragments by polyacrylamide
      gel analysis. Some of the minifragments in viral DNA were present in extramolar
      amounts and corresponded in size to some of the minifragments present in HindIII
      L and -Q. Clones of some of the EcoRI minifragments were used as probes in
      hybridizations to digests of viral DNA and of HindIII-L and -Q. The hybridization
      data, obtained under various levels of stringency, suggested that there was a
      degree of mismatching between the sequences which were responsible for the
      homology.

PMID- 16789238
TI  - Structural and Intracellular Proteins of the Nonoccluded Baculovirus HZ-1.
AB  - A plaque-purified isolate of the baculovirus HZ-1 was used to examine the
      kinetics of replication of this persistent, nonoccluded virus in TN-368 cells.
      Twenty-eight virus structural proteins ranging in molecular weight from 153,000
      to 14,000 were identified. Fourteen of these proteins were found to be
      glycosylated. The sequence of appearance of the 37 virus-induced intracellular
      polypeptides was determined by pulse-labeling with [(35)S]methionine. N
      [(3)H]acetylglucosamine, [(3)H]mannose, and the glycosylation inhibitor
      tunicamycin were used to detect virus structural glycoproteins. Post
      transcriptional modification of two virus-induced proteins was detected.

PMID- 16789239
TI  - Occluded and Budded Autographa californica Nuclear Polyhedrosis Virus:
      Immunological Relatedness of Structural Proteins.
AB  - The immunological relatedness of the structural proteins of the budded and
      occluded phenotypes of Autographa californica nuclear polyhedrosis virus was
      examined by reciprocal immunoblotting and by in situ peroxidase-antiperoxidase
      staining of virus-induced cell surface and intracellular antigens with antisera
      to both phenotypes. The molecular weights (MWs) of major structural proteins of
      both phenotypes that reciprocally cross-reacted were 92,500, 78,000, 62,500,
      54,000, and 42,000. A highly immunogenic, major structural protein of the
      occluded phenotype of 46,000 MW was not recognized by antiserum to the budded
      phenotype, and a major structural protein of the budded phenotype, 48,000 MW, was
      not recognized by antiserum to the occluded phenotype. Both the budded and
      occluded phenotypes contained a protein of 33,500 MW that comigrated with
      polyhedrin (the matrix protein) and reacted with antiserum and monoclonal
      antibody to polyhedrin. Evidence was obtained for the apparent antigenic
      relatedness of proteins of different MWs from the budded and occluded phenotypes,
      possibly indicative of different processing of some proteins for the two
      phenotypes. Antiserum to the occluded phenotype recognized virus-induced cell
      surface antigens, indicating antigenic similarities between the occluded
      phenotype and envelope proteins of the budded phenotype. Antiserum to the budded
      phenotype recognized viral proteins produced before the appearance of cytopathic
      effect, whereas antiserum to the occluded phenotype did not.

PMID- 16789240
TI  - Protein Kinase Activity Associated with the Extracellular and Occluded Forms of
      the Baculovirus Autographa californica Nuclear Polyhedrosis Virus.
AB  - Protein kinase activity is associated with both the extracellular and the
      occluded forms of Autographa californica nuclear polyhedrosis virus, a
      baculovirus. Serine and threonine are the predominant amino acids phosphorylated
      by the kinase activity associated with both viral forms; no phosphotyrosine was
      detected. The addition of calcium, cAMP, or cGMP has no apparent effect on the
      amount of phosphorylation or the substrates phosphorylated.

PMID- 16789241
TI  - Autonomous replication and expression of RNA 1 from black beetle virus.
AB  - Black beetle virions contain two RNAs. The smaller one, RNA 2, has previously
      been shown to be a messenger for viral coat protein. It is shown here, by
      infecting sensitized Drosophila cells with the individually purified RNAs, that
      the larger one, RNA 1, carries the viral gene(s) required for RNA polymerase
      functions. RNA 2 was dispensible for synthesis of viral RNA 1 and subgenomic RNA
      3 but was essential for synthesis of RNA 2 and virions. Cells infected with RNA 1
      alone produced RNA 3 in proportions 10- to 20-fold greater than cells infected
      with virions. This overproduction of RNA 3 decreased with increasing proportions
      of RNA 2 in the infecting RNA 1. We conclude that RNA 1 is the previously
      unidentified progenitor of subgenomic RNA 3, whereas RNA 2 regulates the amount
      of RNA 3 produced in the infected cell.

PMID- 16789242
TI  - Molecular Engineering of the Autographa californica Nuclear Polyhedrosis Virus
      Genome: Deletion Mutations Within the Polyhedrin Gene.
AB  - We describe a method to introduce site-specific mutations into the genome of
      Autographa californica nuclear polyhedrosis virus. Specifically, the A.
      californica nuclear polyhedrosis virus gene for polyhedrin, the major protein
      that forms viral occlusions in infected cells, was mutagenized by introducing
      deletions into the cloned DNA fragment containing the gene. The mutagenized
      polyhedrin gene was transferred to the intact viral DNA by mixing fragment and
      viral DNAs, cotransfecting Spodoptera frugiperda cells, and screening for viral
      recombinants that had undergone allelic exchange. Recombinant viruses with mutant
      polyhedrin genes were obtained by selecting the progeny virus that did not
      produce viral occlusions in infected cells (occlusion-negative mutants). Analyses
      of occlusion-negative mutants demonstrated that the polyhedrin gene was not
      essential for the production of infectious virus and that deletion of certain
      sequences within the gene did not alter the control, or decrease the level of
      expression, of polyhedrin. An early viral protein of 25,000 molecular weight was
      apparently not essential for virus replication in vitro, as the synthesis of this
      protein was not detected in cells infected with a mutant virus.

PMID- 16789243
TI  - Orientation of the cleavage map of the 200-kilodalton polypeptide encoded by the
      bottom-component RNA of cowpea mosaic virus.
AB  - The genomic organization of the bottom-component RNA of cowpea mosaic virus was
      studied. In vivo, this RNA encodes at least eight different polypeptides of 170,
      110, 87, 84, 60, 58, 32, and 4 kilodaltons (K), the last polypeptide representing
      the genome-bound protein VPg. In rabbit reticulocyte lysates, bottom-component
      RNA is translated into a 200K polypeptide which is then processed to give the 32
      and 170K polypeptides also found in vivo. By pulse-labeling the 200K primary
      translation product, we now show that the 32 and 170K polypeptides are derived
      from the NH(2)-terminal and COOH-terminal parts of this polypeptide,
      respectively. Comparison of the proteolytic peptide patterns of 170K polypeptides
      synthesized in vitro and pulse-labeled at either the NH(2)-terminal or the COOH
      terminal end with the patterns of the 170 and 110K polypeptides found in vivo
      demonstrates that the order within the 200K primary translation product of cowpea
      mosaic virus bottom-component RNA is as follows: NH(2)-32K polypeptide-58K
      polypeptide-VPg-24K polypeptide-87K polypeptide-COOH.

PMID- 16789244
TI  - Acquisition of Host Cell DNA Sequences by Baculoviruses: Relationship Between
      Host DNA Insertions and FP Mutants of Autographa californica and Galleria
      mellonella Nuclear Polyhedrosis Viruses.
AB  - Mutants of Autographa californica and Galleria mellonella nuclear polyhedrosis
      viruses, which produce an altered plaque phenotype as a result of reduced numbers
      of viral occlusions in infected cells, were isolated after passage in
      Trichoplusia ni (TN-368) cells. These mutants, termed FP (few-polyhedra) mutants,
      had acquired cell DNA sequences ranging from 0.8 to 2.8 kilobase pairs in size.
      The insertions of cell DNA occurred in a specific region between 35.0 and 37.7
      map units of the A. californica viral genome. A cloned viral fragment containing
      one of the host DNA inserts was homologous to host DNA inserts in two other
      mutant viruses and to dispersed, repetitious sequences in T. ni cell DNA. Most of
      the homology between the cloned insert and cell DNA was contained within a 1,280
      base-pair AluI fragment. Marker rescue studies and analysis of infected-cell
      specific proteins suggested that the insertion of cell DNA into the viral genomes
      resulted in the FP plaque phenotype, possibly through the inactivation of a
      25,000-molecular-weight protein.

PMID- 16789245
TI  - Expression of Campoletis sonorensis Virus in the Parasitized Host, Heliothis
      virescens.
AB  - Polyadenylated mRNA transcripts of the virus of Campoletis sonorensis were
      detected in Heliothis virescens host larvae 2 h after the larvae had been
      parasitized by C. sonorensis females and continued to be present in host larvae
      through 9 days postparasitization while C. sonorensis developed
      endoparasitically. cDNAs of viral transcripts present in H. virescens hybridized
      with only certain C. sonorensis viral DNAs.

PMID- 16789246
TI  - Viral Transcription During Autographa californica Nuclear Polyhedrosis Virus
      Infection: a Novel RNA Polymerase Induced in Infected Spodoptera frugiperda
      Cells.
AB  - Autographa californica nuclear polyhedrosis virus-specific RNA synthesis in
      isolated nuclei of Spodoptera frugiperda cells in culture was monitored at
      different times postinfection. Up to 8 h postinfection viral RNA synthesis
      remained sensitive to 5 mug of alpha-amanitin per ml. During the course of
      infection this sensitivity decreased, and at 24 h postinfection RNA synthesis was
      completely resistant to alpha-amanitin. DEAE-Sephadex profiles of RNA polymerase
      isolated at 24 h postinfection showed a new, chromatographically distinct, alpha
      amanitin-resistant form whose kinetics and response to divalent cations differed
      from those of the host RNA polymerases. The possibility that this enzyme may be
      responsible for viral late transcription is discussed.

PMID- 16789247
TI  - DNA analysis of insect iridescent virus 6: evidence for circular permutation and
      terminal redundancy.
AB  - DNA analysis of small insect iridovirus 6 was performed. Combined exonuclease
      restriction endonuclease digestions revealed that all resulting fragments were
      degraded without preference for any one DNA fragment. Upon denaturation and
      reannealing of native linear Chilo iridescent virus DNA (158 x 10(6) daltons),
      duplex DNA circles of a smaller size (140 x 10(6) daltons) with protruding tails
      were formed.

PMID- 16789248
TI  - Evidence That the 32,000-Dalton Protein Encoded by Bottom-Component RNA of Cowpea
      Mosaic Virus is a Proteolytic Processing Enzyme.
AB  - Translation of middle-component RNA of cowpea mosaic virus in vitro produced two
      polypeptides of 95 and 105 kilodaltons (95K and 105K, respectively) with
      overlapping amino acid sequences, which were specifically cleaved by a protease
      encoded by the bottom-component RNA. The proteolytic cleavage was studied by the
      addition of antibodies raised against various bottom-component RNA-encoded
      proteins to extracts prepared from bottom-component RNA-inoculated cowpea
      protoplasts. Since antiserum to the 32K polypeptide efficiently inhibited the
      proteolytic activity of such extracts, although antiserum to VPg or to the 170K
      polypeptide did not, evidence was obtained which indicates that the 32K
      polypeptide represents the protease involved. Fractionation of proteolytically
      active extract by glycerol gradient centrifugation demonstrated that 32K
      polypeptides do not exist as free proteins but are aggregated to the bottom
      component RNA-encoded 170K, 84K, 60K, or 58K polypeptides. Maximal proteolytic
      activity was observed for 32K polypeptides associated with 170K polypeptides,
      suggesting that the activity was unstable and confined to newly synthesized
      molecules.

PMID- 16789249
TI  - Mapping of Early and Late Transcripts Encoded by the Autographa californica
      Nuclear Polyhedrosis Virus Genome: Is Viral RNA Spliced?
AB  - Early and late transcripts were mapped on the Autographa californica nuclear
      polyhedrosis virus genome by Northern blotting and hybridization with the cloned
      viral EcoRI fragments. At least 11 early and about 90 late RNAs were compared
      with over 32 polypeptides synthesized by in vitro translation of hybrid-selected
      RNA. The latter method, of course, had its limitations also and did not guarantee
      that all viral RNAs could be detected in this way. A comparison of cytoplasmic
      and total cellular RNAs showed no clear-cut differences in their size
      distributions. We found that there were more RNA classes than corresponding
      proteins encoded by them and mapped by in vitro translation. By using the Berk
      Sharp method and analyses of DNA-RNA hybrids by one-dimensional or two
      dimensional neutral and alkaline gel electrophoreses, we were unable to adduce
      evidence for RNA splicing in this viral system. Minor splices, particularly at
      sites close to the termini of RNA molecules, could not be excluded.

PMID- 16789250
TI  - Time Course Analysis and Mapping of Autographa californica Nuclear Polyhedrosis
      Virus Transcripts.
AB  - To study the expression of the Autographa californica nuclear polyhedrosis virus
      (AcNPV) genome, intracellular virus-specific proteins and mRNAs were pulsed
      labeled, extracted, and analyzed at 6-h intervals during the replicative cycle.
      Most RNAs were detected between 12 and 24 h postinfection (p.i.), but many
      continued to be synthesized until late in infection. Polyhedrin and p8 mRNAs were
      the two most abundant late viral RNA transcripts, and they were synthesized at
      high rates until late in the infection cycle (60 h p.i.). The abundancy control
      of polyhedrin and p8 polypeptides was considered to be at the level of
      transcription. Two other major mRNAs in infected cells were 0.6-kilobase RNA,
      which was synthesized at its highest rate 12 to 18 h p.i., and 2.8-kilobase RNA,
      which was synthesized from 12 h p.i. until 48 h p.i. Cytoplasmic polyadenylic
      acid-containing RNA was isolated at 6-h intervals and was analyzed by Northern
      blot hybridization. At least 50 virus RNA transcripts were recognized, sized, and
      mapped onto the genome. Six RNAs hybridized to EcoRI-H, -I, and -J, and HindIII-Q
      AcNPV DNA restriction fragments, seven RNAs hybridized to EcoRI-B and -D DNA
      fragments, five RNAs hybridized to EcoRI-A and -E regions of the genome, four
      RNAs hybridized to EcoRI-C and -N DNA fragments, and one RNA species hybridized
      to EcoRI-O AcNPV DNA. A transcription map of the AcNPV genome was constructed,
      and the data were correlated with previously published translation maps.

PMID- 16789251
TI  - Protein Synthesis in a Lymantria dispar Cell Line Infected by Cytoplasmic
      Polyhedrosis Virus.
AB  - The efficiency of replication of a cytoplasmic polyhedrosis virus isolated from a
      member of the order Lepidoptera, Euxoa scandens, was studied in eight different
      lepidopterean cell lines. Lymantria dispar cells, which were found to support
      viral replication, more efficiently, were used to follow the kinetics of
      appearance of viral-specific polypeptides by a 2-h pulse with [(35)S]methionine.
      Five polypeptides (ca. 120,000 molecular weight [120K], 105K, 66K, 46K, and 28K)
      were identified as components of the polyhedral inclusion bodies, and two
      polypeptides (112K and 39K) were assigned as viral-particle polypeptides. All
      these polypeptides were present after 24 h and were still being produced 96 h
      after infection. The rate of synthesis of the major polyhedral polypeptide (28K)
      increased in the time course of infection, whereas the background of cellular
      polypeptides seemed to be unaffected. An indirect immunoperoxidase technique,
      after sodium dodecyl sulfate-polyacrylamide gel electrophoresis was blotted to a
      nitrocellulose membrane, showed that traces of the major polyhedral polypeptide
      were found from 8 h postinfection.

PMID- 16789252
TI  - Phosphorylation of the beta' Subunit of RNA Polymerase and Other Host Proteins
      upon phiCd1 Infection of Caulobacter crescentus.
AB  - A protein kinase activity is induced early after infection of Caulobacter
      crescentus by the DNA phage phiCd1. After phage infection at least 40 proteins
      are phosphorylated; these include DNA-binding proteins, a membrane-associated
      protein, and several ribosomal proteins. One of the phosphorylated DNA-binding
      proteins was identified as the beta' subunit of the host RNA polymerase.

PMID- 16789253
TI  - Semipermissive Replication of a Nuclear Polyhedrosis Virus of Autographa
      californica in a Gypsy Moth Cell Line.
AB  - Several gypsy moth cell lines have been previously described as nonpermissive for
      the multiple-embedded nuclear polyhedrosis virus of Autographa californica
      (AcMNPV). In this report, we demonstrate the semipermissive infection of a gypsy
      moth cell line, IPLB-LD-652Y, with AcMNPV. IPLB-LD-652Y cells infected with
      AcMNPV produced classic cytopathic effects but failed to yield infectious progeny
      virus. Results of experiments employing DNA-DNA dot hybridization suggested that
      AcMNPV DNA synthesis was initiated from 8 to 12 h postinfection (p.i.), continued
      at a maximum rate from 12 to 20 h p.i., and declined from 20 to 36 h p.i. The
      rate of AcMNPV DNA synthesis approximated that observed in the permissive TN-368
      cell line. AcMNPV-infected IPLB-LD-652Y cells, pulse-labeled with
      [(35)S]methionine at various time intervals p.i. and analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, revealed four virus-induced proteins,
      one novel to the semipermissive system and three early alpha proteins,
      synthesized from 1 to 20 h p.i. Thereafter, both host and viral protein synthesis
      was completely suppressed. These results suggest that AcMNPV adsorbed,
      penetrated, and initiated limited macromolecular synthesis in the semipermissive
      gypsy moth cell line. However, the infection cycle was restricted during the
      early phase of AcMNPV replication.

PMID- 16789254
TI  - Identification, Mapping, and In Vitro Translation of Campoletis sonorensis Virus
      mRNAs from Parasitized Heliothis virescens Larvae.
AB  - Expression of Campoletis sonorensis virus (CsV) in parasitized Heliothis
      virescens larvae was investigated by Northern blot analysis of poly(A)(+) mRNAs
      isolated from H. virescens larvae at various times after parasitization by C.
      sonorensis. At least 12 CsV mRNAs were detected in parasitized H. virescens
      larvae. Injection of nonparasitized H. virescens larvae with purified CsV
      resulted in a pattern of viral mRNAs similar to that observed in naturally
      parasitized larvae. With CsV DNA restriction fragments which contained expressed
      sequences, individual CsV mRNAs were mapped to the superhelical DNAs of the viral
      genome. Two gene-specific probes, which consisted of cloned S1 nuclease-protected
      restriction fragments, each hybridized to several CsV superhelical DNAs,
      suggesting that some CsV genes may be shared on several superhelical DNAs. Cloned
      restriction fragments containing sequences which flank the expressed sequences
      also hybridized to numerous CsV superhelical DNAs. Some CsV proteins were
      identified by in vitro translation of hybrid-selected CsV mRNAs.

PMID- 16789255
TI  - Campoletis sonorensis Endoparasitic Wasps Contain Forms of C. sonorensis Virus
      DNA Suggestive of Integrated and Extrachromosomal Polydnavirus DNAs.
AB  - Campoletis sonorensis virus (CsV) (Polydnaviridae) previously was detected only
      in the calyx epithelial cells and lumen of the oviducts from female C. sonorensis
      (Ichneumonidae) endoparasitic wasps (Norton et al., Cell Tissue Res. 162:195-208,
      1975). Using dot-blot hybridizations, we detected low amounts of CsV DNA in male
      and female wasp head and thorax tissues and in male abdominal tissues. Low
      amounts of extrachromosomal viral DNA were detected in Southern blots of
      undigested male wasp DNA and in male DNA purified by isopycnic centrifugation.
      High-molecular-weight male wasp DNA digested with any of several restriction
      endonucleases and hybridized with cloned viral DNAs from CsV superhelices B and Q
      under stringent conditions contained CsV-specific DNA fragments that differed
      significantly in size and number from the hybridizing fragments detected in
      comparably digested viral DNA. Identical offsize restriction fragments were
      detected in digested female head and thorax DNA. These data suggest that at least
      CsV DNAs B and Q are integrated in C. sonorensis cellular DNA and that the virus
      may be transmitted through the germline.

PMID- 16789256
TI  - Synthesis of Double-Stranded RNA in a Virus-Enriched Fraction from Agaricus
      bisporus.
AB  - Partially purified virus preparations from sporophores of Agaricus bisporus
      affected with LaFrance disease had up to a 15-fold-higher RNA-dependent RNA
      polymerase activity than did comparable preparations from healthy sporophores.
      Enzyme activity was dependent upon the presence of Mg(2+) and the four nucleoside
      triphosphates and was insensitive to actinomycin D, alpha-amanitin, and rifampin.
      The (3)H-labeled enzyme reaction products were double-stranded RNA (dsRNA) as
      indicated by CF-11 cellulose column chromatography and by their ionic-strength
      dependent sensitivity to hydrolysis by RNase A. The principal dsRNA products had
      estimated molecular weights of 4.3 x 10(6) and 1.4 x 10(6); they corresponded in
      size and hybridized to the major dsRNAs detected in the virus preparation by
      ethidium bromide staining. Cs(2)SO(4) equilibrium centrifugation of the virus
      preparation resolved a single peak of RNA polymerase activity that banded with a
      35-nm spherical virus particle containing dsRNAs with molecular weights of 4.3 x
      10(6) and 1.4 x 10(6). The data suggest that the RNA-dependent RNA polymerase
      associated with the 35-nm spherical virus is a replicase which catalyzes the
      synthesis of the genomic dsRNAs.

PMID- 16789257
TI  - Determination of the proteolytic processing sites in the polyprotein encoded by
      the bottom-component RNA of cowpea mosaic virus.
AB  - The bottom-component RNA (B-RNA) of cowpea mosaic virus is expressed by the
      production of a approximately 200,000-dalton polyprotein (200K polyprotein), from
      which the functional proteins are formed by specific proteolytic cleavages.
      Partial amino-terminal sequences of the various B-RNA-encoded proteins have now
      been determined. Comparison of the information obtained with the B-RNA sequence
      allowed the localization of the coding regions for these proteins on B-RNA, the
      calculation of their precise molecular weights, and the determination of the
      cleavage sites at which they are released from the polyprotein precursor.
      Sequence analysis of the 32K protein, which is derived from the amino-terminal
      end of the 200K polyprotein, indicated that the AUG codon at nucleotide position
      207 of the RNA sequence is the translation initiation codon. Sequence analysis of
      the 170K, 110K, 87K, 84K, 60K, and 58K proteins revealed the existence of three
      types of cleavage site in the 200K polyprotein: glutamine-serine (two sites),
      glutamine-methionine (one site), and glutamine-glycine (one site) amino acid
      pairs. The nature of these cleavage sites suggested that two different viral
      proteases are involved in the processing of the B-RNA-encoded polyprotein.

PMID- 16789258
TI  - Interspersed Homologous DNA of Autographa californica Nuclear Polyhedrosis Virus
      Enhances Delayed-Early Gene Expression.
AB  - The five regions of homologous DNA which are interspersed in the genome of the
      baculovirus Autographa californica nuclear polyhedrosis virus increased the
      expression of a delayed-early gene of this virus. Although this activity was
      first observed as a 10-fold trans effect, the homologous region 5 (hr5) enhanced
      the expression of linked genes 1,000-fold. The hr5 enhancer also exhibited the
      other characteristics associated with viral enhancer elements, including
      orientation independence and the abilities to function at a distance from the
      linked promoter, to regulate heterologous promoters, and to increase the number
      of RNA polymerase molecules transcribing the linked genes. The expression of the
      immediate-early regulatory gene was not enhanced by cis-linked hr5, although the
      enhancer function may require the immediate-early regulatory gene product. The
      hr5 enhancer was relatively insensitive to competition by an excess of enhancer
      molecules. The nucleotide sequence of hr5 revealed two different conserved
      repeats separated by nonhomologous DNA. Deletion analysis of the hr5 enhancer
      indicated that a 30-base-pair inverted repeat was essential for enhancer
      function.

PMID- 16789259
TI  - Complete Sequence and Enhancer Function of the Homologous DNA Regions of
      Autographa californica Nuclear Polyhedrosis Virus.
AB  - The nucleotide sequence of the five regions of homologous DNA in the genome of
      Autographa californica nuclear polyhedrosis virus DNA was determined. The
      homology of repeated sequences within a region was 65 to 87%, and the consensus
      sequences for each region were 88% homologous to each other. Sequences proximal
      to the EcoRI sites were most conserved, while the distal sequences were least
      conserved. The EcoRI sites formed the core of a 28-base-pair imperfect inverted
      repeat. All homologous regions functioned as enhancers in a transient expression
      assay. A single EcoRI minifragment located between EcoRI-Q and -L enhanced the
      expression of 39CAT as efficiently as the regions containing numerous EcoRI
      repeats did.

PMID- 16789260
TI  - Two-Dimensional Polyacrylamide Gel Analysis of Plodia interpunctella Granulosis
      Virus.
AB  - The structural polypeptides of purified Plodia interpunctella granulosis virus
      were analyzed by three different two-dimensional gel systems. Isoelectric
      focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      allowed resolution of 53 acidic polypeptides in the enveloped nucleocapsid of the
      virus ranging in molecular weight from 97,300 to 8,000. Nine of these
      polypeptides were shown to be glycoproteins by the technique of radiolabeled
      lectin blotting. Separation of the granulin in this system allowed resolution of
      five species, all of which have identical tryptic peptide maps. This matrix
      protein was demonstrated to be a phosphoglycoprotein by radiolabeled lectin
      blotting and acid phosphatase dephosphorylation. Nonequilibrium pH gel
      electrophoresis followed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis allowed resolution of the major basic protein of the virus, VP12,
      from a more acidic protein of the same molecular weight. Tryptic peptide analysis
      demonstrated that these two proteins were indeed different and acid urea gels
      followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis allowed
      localization of the acidic protein to the envelope and the basic protein to the
      nucleocapsid of the virus. Finally, probing of the separated envelope
      nucleocapsid proteins in both the isoelectric focusing and nonequilibrium pH gel
      electrophoresis two-dimensional systems after transfer to nitrocellulose with
      iodinated, purified viral proteins allowed further insight into reactions which
      may be important in the maintenance of the virion structure.

PMID- 16789261
TI  - DNA Synthesis in Tobacco Mosaic Virus-Infected Nicotiana tabacum Protoplasts and
      Regeneration of Persistently Infected Calli.
AB  - Tobacco mosaic virus infection of Nicotiana tabacum mesophyll protoplasts did not
      affect the pattern of chloroplast or total cellular DNA synthesis for at least
      120 h when compared with that of mock-infected cells. Calli derived from infected
      protoplasts often showed large amounts of tobacco mosaic virus RNA and coat
      protein.

PMID- 16789262
TI  - Detection of a Novel Protein Encoded by the Bottom-Component RNA of Cowpea Mosaic
      Virus, Using Antibodies Raised against a Synthetic Peptide.
AB  - A peptide was synthesized that corresponded to a sequence in the cowpea mosaic
      virus bottom-component RNA-encoded 200-kilodalton polyprotein showing homology to
      the picornaviral 3C proteases. By injecting a rabbit with this peptide,
      antibodies were obtained that allowed the detection of a novel viral protein
      derived from the 200-kilodalton polyprotein. This protein, which had a size of 24
      kilodaltons was found in both infected cowpea leaves and cowpea protoplasts.

PMID- 16789263
TI  - Inhibition of cleavage of a plant viral polyprotein by an inhibitor activity
      present in wheat germ and cowpea embryos.
AB  - In rabbit reticulocyte lysate, the bottom component RNA of cowpea mosaic virus
      directs the synthesis of a 200,000-molecular-weight precursor protein (200K
      protein) that is cleaved during synthesis by a reticulocyte enzyme to form a 32K
      protein and a 170K protein. Cleavage of the 200K protein was found to be
      effectively inhibited by inhibitor activity in wheat germ and cowpea embryo
      extracts. The inhibitor was nondialyzable, precipitatable by ammonium sulfate,
      and partially stable at high temperatures. The activity appeared to be specific
      in that it caused no inhibition of the secondary cleavage reactions (cleavage of
      the 170K protein) at concentrations that were sufficient to cause complete
      inhibition of the primary cleavage reaction (cleavage of the 200K protein).

PMID- 16789264
TI  - Nucleotide sequence and temporal expression of a baculovirus regulatory gene.
AB  - The nucleotide sequence of a trans-activating regulatory gene (IE-1) of the
      baculovirus Autographa californica nuclear polyhedrosis virus has been
      determined. This gene encodes a protein of 581 amino acids with a predicted
      molecular weight of 66,856. A DNA fragment containing the entire coding sequence
      of IE-1 was inserted downstream of an RNA promoter. Subsequent cell-free
      transcription and translation directed the synthesis of a single peptide with an
      apparent molecular weight of 70,000. Quantitative S1 nuclease analysis indicated
      that IE-1 was maximally synthesized during a 1-h virus adsorption period and that
      steady-state levels of IE-1 message were maintained during the first 24 h of
      infection. Northern blot hybridization indicated that several late transcripts
      which overlap the IE-1 gene were transcribed from both strands. The precise
      locations of the 5' and 3' ends of these overlapping transcripts were mapped
      using S1 nuclease. The overlapping transcripts were grouped in two
      transcriptional units. One unit was composed of IE-1 and overlapping gamma
      transcripts which initiated upstream of IE-1 and terminated downstream of IE-1.
      The other unit, transcribed from the opposite strand, consisted of gamma
      transcripts with coterminal 5' ends and extended 3' ends. The shorter, more
      abundant transcripts in this unit overlapped 30 to 40 bases of IE-1 at the 3'
      end, while the longer transcripts overlapped the entire IE-1 gene. Transcription
      of several early A. californica nuclear polyhedrosis virus genes, in addition to
      39K, was shown to be trans-activated by IE-1, indicating that IE-1 may have a
      central role in the regulation of beta-gene expression.

PMID- 16789265
TI  - Small nuclear inclusion protein encoded by a plant potyvirus genome is a
      protease.
AB  - Tobacco etch virus, a plant potyvirus, expresses its RNA genome as a large
      polyprotein precursor which undergoes extensive proteolytic processing to yield
      seven or more mature products. Two of these products, proteins with apparent
      molecular weights of 49,000 and 54,000 (49K and 54K proteins), aggregate in the
      form of crystalline inclusions within the nuclei of infected cells. Cell-free
      translation of synthetic transcripts was used to map the genes for these two
      products on the viral genome and to express an enzymatically active protein. The
      49K protein was determined to be a viral protease responsible for several
      cleavages of the polyprotein, including its own autocatalytic excision. Analyses
      of products expressed from the 49K protein genes which were altered by deletion
      revealed that only the carboxyl-terminal half was required for proteolytic
      activity.

PMID- 16789266
TI  - Physical Analysis of the Campoletis sonorensis Virus Multipartite Genome and
      Identification of a Family of Tandemly Repeated Elements.
AB  - This report is an analysis of cross-hybridizing sequences found within the 28
      superhelical (SH) DNAs of the multipartite genome of the polydnavirus Campoletis
      sonorensis virus (CsV). A Southern cross-blot hybridization analysis showed that
      the majority of CsV EcoRI restriction fragments cross-hybridize to multiple EcoRI
      fragments. These sequence homologies were analyzed by hybridizing recombinant
      clones of the CsV SH DNAs B, H, M, and O(1) to Southern blots of undigested CsV
      DNA, using different hybridization stringencies. The results indicated that
      homologous regions among the SH DNAs include closely related sequences that are
      detectable under stringent conditions and related but more diverged sequences
      which are only detectable under reduced stringencies. A sequence that hybridized
      to the majority of the CsV SH DNAs was identified and subcloned from the SH DNAs
      O(1), H, and B. Nucleotide sequence data revealed that these homologous regions
      contained a family of imperfectly conserved repeated elements. These repeat
      elements were arranged singly or in direct tandem arrays and had an average
      length of 540 base pairs. Within the sequenced regions that contained the
      repeated elements six putative open reading frames were identified. These results
      show that the CsV genome consists of SH DNAs with complex sequence
      interrelationships that may have arisen due to multiple recombinational events.

PMID- 16789268
TI  - Identification of nonfermentative bacilli.

PMID- 16789267
TI  - Revised Nomenclature of Alloiococcus otitis.

PMID- 16789269
TI  - Isolation of Campylobacter jejuni from Patients with Diarrhea.

PMID- 16789270
TI  - Increased Efficiency of Group B Coxsackievirus Isolation from Clinical Specimens
      by Use of BGM Cells.
AB  - A continuous African green monkey kidney cell line, designated BGM, was compared
      with primary cynomolgus monkey kidney cells and human embryonic lung cells for
      efficiency of enterovirus isolation. A selective enhanced sensitivity of BGM
      cells both in terms of isolation rate and speed of isolation was found for group
      B coxsackieviruses but could not be demonstrated for a number of other nonpolio
      enteroviruses.

PMID- 16789271
TI  - Comparison of passive hemagglutination with Turkey erythrocyte assay, enzyme
      linked immunosorbent assay, and counterimmunoelectrophoresis assay for
      serological evaluation of tetanus immunity.
AB  - Antibody titers to tetanus toxin in human sera were assayed by passive
      hemagglutination with turkey erythrocytes, enzyme-linked immunosorbent assay, and
      counterimmunoelectrophoresis. The first two of these tests were shown to be the
      most sensitive for antibody detection, having the same range of sensitivity and
      reproducibility. The antibody levels determined by these assays were up to 400
      fold higher than those determined by counterimmunoelectrophoresis. The turkey
      erythrocyte hemagglutination assay requires only 40 min, whereas the
      immunosorbent assay method requires 24 h. These results suggest that the
      hemagglutination assay is the more appropriate method for rapid and sensitive
      determination of tetanus antibody levels.

PMID- 16789272
TI  - Corrected version specificity of the latex test for cryptococcal antigen: a
      rapid, simple method for eliminating interference factors.
AB  - An enzymatic method involving a protease (pronase) for the elimination of
      interference factors in the latex test for cryptococcal antigen was developed and
      compared with dithiothreitol treatment. The two were equivalent in their ability
      to remove interference factors; however, the enzymatic method generally yielded
      higher titers. The method is simple, requires only 20 min, and makes the latex
      test for cryptococcal antigen specific.

PMID- 16789273
TI  - HIV vaccine database launched.

PMID- 16789274
TI  - Funding. Senate committee passes CARE Act reauthorization bill.

PMID- 16789275
TI  - Global. United States barred from placing condition on AIDS funds.

PMID- 16789276
TI  - San Francisco health agencies move to streamline HIV testing.

PMID- 16789277
TI  - Prevention. Public advocate survey reveals problems at city STD clinics.

PMID- 16789278
TI  - Disclosure. Judge: request for HIV/AIDS records is "fishing expedition".

PMID- 16789279
TI  - Disclosure. Jailers must pay legal fees for probing detainee's serostatus.

PMID- 16789280
TI  - Court orders prison officials to disclose HIV policies.

PMID- 16789281
TI  - Los Angeles County supervisors halt cuts to AIDS services.

PMID- 16789282
TI  - Prevention. Vatican ponders condoms to prevent HIV in marriage.

PMID- 16789283
TI  - Transmission. Court upholds ruling against woman who contracted HIV.

PMID- 16789284
TI  - HIV and methamphetamines. Canadian group describes link between crystal meth and
      HIV.

PMID- 16789285
TI  - Appeals court hears debate in HIV discrimination case.

PMID- 16789286
TI  - Denial of SSI benefits overturned for HIV-positive man.

PMID- 16789287
TI  - ADA. Paralyzed, HIV-positive inmate awarded $200 in damages.

PMID- 16789288
TI  - Discrimination. ALJ's termination upheld after making HIV slurs.

PMID- 16789289
TI  - HIV and race. Conference addresses impact of HIV on Native Americans.

PMID- 16789290
TI  - A second life for cloning.

PMID- 16789291
TI  - A silent scientist under fire.

PMID- 16789292
TI  - The moral status of animals.

PMID- 16789293
TI  - Biomedical samples from the Amazon.

PMID- 16789294
TI  - Sense of injustice can lead scientists to act unethically, study finds.

PMID- 16789295
TI  - Researchers raise concerns about secrecy in company-sponsored clinical trials.

PMID- 16789296
TI  - Animal-rights groups fight colleges over access to research records.

PMID- 16789297
TI  - The licit use of methotrexate.

PMID- 16789298
TI  - Management of extrauterine pregnancy.

PMID- 16789299
TI  - In moral labor.

PMID- 16789300
TI  - Expanding databases, declining liberties.

PMID- 16789301
TI  - Essentially yours: the protection of human genetic information in Australia.

PMID- 16789302
TI  - The monster's laws: a legal history of chimera research.

PMID- 16789303
TI  - Case study: agency says institutional review board (IRB) failed to warn subjects
      of significant problems.

PMID- 16789304
TI  - Research subjects win battle to obtain class action suits.

PMID- 16789305
TI  - How institutional review boards (IRBs) can handle adverse event reports.

PMID- 16789306
TI  - Case study: research subject says institutional review board (IRB) was no help.

PMID- 16789307
TI  - In court: research subjects says institutional review boards (IRBs) must change
      research review.

PMID- 16789308
TI  - Minority groups as human subjects.

PMID- 16789309
TI  - Case study: research subject says institutional review board (IRB) would not
      answer her questions.

PMID- 16789310
TI  - Defendants claim that research subjects do not qualify for class action lawsuit.

PMID- 16789311
TI  - The age of neuroelectronics.

PMID- 16789312
TI  - Who owns the genome?

PMID- 16789313
TI  - Human cloning and scientific corruption: the South Korea scandal and the future
      of the stem cell debate.

PMID- 16789315
TI  - Hwang's forgotten crime: the exploitation of women is a far worse offence than
      data fabrication.

PMID- 16789316
TI  - The Domesday project: how much personal information should we reveal for the
      common good?

PMID- 16789318
TI  - Who is messing with your head?

PMID- 16789317
TI  - One million people, one medical gamble.

PMID- 16789319
TI  - Animal rights and wrongs.

PMID- 16789320
TI  - Miracle postponed.

PMID- 16789321
TI  - Stand up and be counted.

PMID- 16789322
TI  - Surviving interests and living wills.

PMID- 16789323
TI  - Ask TMA. Should I opt out of Medicare?

PMID- 16789324
TI  - Tobacco use by Native North Americans: sacred smoke and silent killer. [Review
      of: Winter, J.C., ed., Tobacco use by Native North Americans: sacred smoke and
      silent killer. Norman: U. of Oklahoma Pr., 2000].

PMID- 16789326
TI  - Image of the month: Pancreatico-pleural fistula in chronic pancreatitis.

PMID- 16789327
TI  - Cecile M. Pickart (1954-2006).

PMID- 16789328
TI  - NLM offers Household Products Database.

PMID- 16789329
TI  - Colonial Intimacies: Indian Marriage in Early New England. [Review of: Plane,
      A.M., Colonial Intimacies: Indian Marriage in Early New England. Ithaca, N.Y.:
      Cornell U. Pr., 2000].

PMID- 16789330
TI  - Alternative headache therapies.

PMID- 16789331
TI  - Physician and public beliefs about providing life ending drugs.

PMID- 16789332
TI  - Intranasal morphine for postoperative pain.

PMID- 16789333
TI  - National Comprehensive Cancer network adult pain guidelines.

PMID- 16789335
TI  - Physicians and general public support physician-assisted suicide.

PMID- 16789334
TI  - FDA electronic drug labels to improve patient safety.

PMID- 16789336
TI  - Increasing use of the Internet for health care decisions.

PMID- 16789337
TI  - [Functional and cognitive capacity in elderly patients admitted to a general
      Internal Medicine Service].
AB  - OBJECTIVES: To analyze the clinical characteristics, grade of physical and
      cognitive dependence and social coverage of patients of 64 years who are admitted
      to and Internal Medicine Service. DESIGN AND METHODS: A total of 105 patients (63
      females, 42 males) older than 64 years admitted over 2 months in a General
      Internal Medicine Unit of a tertiary University Hospital were studied. RESULTS:
      Fifty nine patients (56%) were 80 years or older. Pulmonary, cardiac and
      gastrointestinal problems were the main reasons for admission. A total of 80% of
      patients had comorbid conditions with a Charlson index of 2.7 +/- 1.4. Mean
      Barthel index before admission was 71+/-35. More than one third of the patients
      had cognitive impairment (MMSE <23/35). Social aid was received by 18% of
      patients. CONCLUSIONS: Patients aged 80 or older with cardiopulmonary disease and
      moderate comorbidity grade are frequently admitted to our General Internal
      Medicine Unit. Physical and cognitive dependence is observed in a significant
      number of our inpatients, but the uses of social-health services are still low in
      our area.

PMID- 16789338
TI  - Practical ethics. MD turns JD.

PMID- 16789339
TI  - [New challenges: general practitioners faced with "rare diseases"].

PMID- 16789340
TI  - History of kala-azar in India. 1947.

PMID- 16789341
TI  - Miner, Preacher, Doctor, Teacher: Stories of an Odyssey from Ann Arbor, Michigan,
      to Ketchikan, Alaska, to a Pioneering Medical Career in Oakland, California.
      [Review of: Loomis, F.C.  Miner, Preacher, Doctor, Teacher: Stories of an Odyssey
      from Ann Arbor, Michigan, to Ketchikan, Alaska, to a Pioneering Medical Career in
      Oakland, California.  Creek, Calif.: Hardscratch Pr., 2000].

PMID- 16789342
TI  - On the possibility of the occurrence of trypanosomiasis in India. 1903.

PMID- 16789343
TI  - Transmission of Indian kala-azar to man by the bites of Phlebotomus argentipes,
      ann and brun. 1942.

PMID- 16789344
TI  - Additive effects of moderate drinking and obesity on serum gamma-glutamyl
      transferase activity.
AB  - BACKGROUND: Gamma-glutamyl transferase (GGT) is a widely used index of liver
      induction and a marker of alcohol overconsumption. Obesity has also been
      suggested to elevate serum GGT activities. OBJECTIVE: The aim was to examine the
      links between moderate ethanol consumption, obesity, and GGT activities. DESIGN:
      GGT values were recorded from 2490 persons (1184 men and 1306 women) who reported
      either no alcohol use (abstainers) or 1-40 g ethanol consumption per day
      (moderate drinkers). The study population was additionally classified according
      to body mass index (BMI; in kg/m2) as follows: < 19 (underweight), > or = 19 and
      < 25 (normal weight), > or = 25 and < 30 (overweight), and 30 (obese). RESULTS:
      Significant main effects of sex (P < 0.0001), drinking habits (P < 0.01), and BMI
      (P < 0.001) on serum GGT activities were observed. The values were higher in the
      men than in the women and higher in those with higher BMIs. The highest
      activities were found to occur in persons with moderate drinking combined with
      overweight or obesity. A significant positive correlation between GGT and BMI (P
      < 0.0001) was observed, which was stronger for the men (r = 0.24) than for the
      women (r = 0.15, P < 0.05 for the difference between correlations). CONCLUSION:
      The data indicate that serum GGT activities may respond to moderate drinking and
      overweight in an additive manner; this should be considered in the clinical use
      of GGT measurements and when defining normal GGT values in health care.

PMID- 16789345
TI  - Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5
      age and sex cohorts.
AB  - BACKGROUND: Evidence is increasing for positive effects of fruit and vegetable
      intakes on bone health. However, most of the studies to date were conducted in
      adults, and few reports included adolescents. OBJECTIVE: We explored the
      association between bone mineral status and fruit and vegetable intakes in
      adolescent boys and girls (aged 16-18 y), young women (aged 23-37 y), and older
      men and women (aged 60-83 y). DESIGN: Bone mineral measurements of the whole
      body, hip, and spine were made in all subjects by using dual-energy X-ray
      absorptiometry. Information on health and lifestyle and physical activity was
      obtained by questionnaire. Fruit, vegetable, and nutrient intakes were
      ascertained from 7-d food diaries. RESULTS: In adolescent boys and girls and
      older women, significant positive associations were observed between spine size
      adjusted bone mineral content (SA-BMC) and fruit intake. In boys only, femoral
      neck SA-BMC was also significantly and positively associated with the intakes of
      both fruit and dietary vitamin C. No significant associations were found in the
      young women or older men, or between bone measurements and intake of vegetables
      alone (after adjustments) in any of the groups. CONCLUSIONS: Higher fruit and
      vegetable intakes may have positive effects on bone mineral status in both
      younger and older age groups, especially at the spine and femoral neck. The
      specific mechanisms remain to be ascertained, but vitamin C, other fruit-specific
      antioxidants, and lifestyle may play a role.

PMID- 16789346
TI  - Special issue of JPMA on HIV/AIDS research publications in Pakistan.

PMID- 16789347
TI  - Things you need to know about blood pressure and hypertension.

PMID- 16789348
TI  - Hospital uses CPOE system to reduce medication errors.

PMID- 16789349
TI  - Methodology may help hospitals evaluate ROI for IT investments.
AB  - Hospitals are spending millions of dollars to install a variety of information
      technology (IT) systems to improve patient care, reduce medication errors and
      track supplies and equipment. But unlike many clinical services, calculating a
      return on investment (ROI) for IT systems is difficult. Researchers at Florida
      State University in Tallahassee may have developed a methodology for hospitals to
      evaluate ROI from a hospital wide perspective.

PMID- 16789350
TI  - Hospital saves lives by reducing ventilator-associated pneumonia.
AB  - Bay Regional Medical Center, Bay City, MI, is one of 14 hospitals participating
      in a national patient safety initiative that has reduced ventilator-associated
      pneumonia (VAP) deaths to zero for at least a year. It took six months before
      staff got used to the new procedures. The real buy-in occurred when they saw the
      evidence.

PMID- 16789351
TI  - Using performance feedback to change provider behavior.
AB  - Although physicians are loathe to admit it, data suggest a majority of them are
      impacted by what researchers refer to as clinical inertia--a failure to initiate
      or intensify therapy when it is clearly indicated. Successful remedies must focus
      on squarely on changing provider behavior.

PMID- 16789352
TI  - I (still) want to be a PA!

PMID- 16789353
TI  - How PAs live and work.

PMID- 16789354
TI  - Paying for performance: an American PA in Britain and the NHS Quality Outcome
      Framework.

PMID- 16789355
TI  - Benign anorectal disease: an update on diagnosis and management.

PMID- 16789356
TI  - Evaluating eosinophilia in the primary care setting.

PMID- 16789357
TI  - Implementing a continuous insulin infusion protocol on a cardiac surgical
      service: a PA's perspective.

PMID- 16789358
TI  - In defense of full disclosure.

PMID- 16789359
TI  - Difficult-to-diagnose pelvic pain.

PMID- 16789360
TI  - A common cause of photodistributed rash.

PMID- 16789361
TI  - Should I be tested for breast cancer genes?

PMID- 16789362
TI  - Patient information. From your physician assistant. Should I be tested for breast
      cancer genes?

PMID- 16789363
TI  - Case of the month. Cervical spondylotic myelopathy.

PMID- 16789364
TI  - Urinary tract infections in infants and children.

PMID- 16789365
TI  - Laboratory investigation for the early diagnosis and monitoring of neonatal
      urinary tract infections: the present situation and future perspectives.

PMID- 16789366
TI  - Clinical pharmacology of antimicrobials for urinary tract infections in newborns
      and young infants.

PMID- 16789367
TI  - Controversies in the antimicrobial treatment of urinary tract infections.

PMID- 16789368
TI  - Cranberry and prevention of urinary tract infections in children.

PMID- 16789369
TI  - Occupational health and safety needs employees and unions.

PMID- 16789370
TI  - Mental health: it's time for action.

PMID- 16789371
TI  - Nurses show leadership by demonstrating a commitment to sound governance.

PMID- 16789372
TI  - Defending nurses against harsh IR laws.

PMID- 16789373
TI  - Turning nursing into a business.

PMID- 16789374
TI  - Management of asymptomatic hypoglycaemia in healthy term neonates for nurses and
      midwives.

PMID- 16789375
TI  - Cultured epithelial autografts.

PMID- 16789376
TI  - Practice nurse wound training.

PMID- 16789377
TI  - Compression therapy--getting it right.

PMID- 16789378
TI  - Nursing the minor thermal burn wound.

PMID- 16789379
TI  - Wound fields and the undergraduate nurse.

PMID- 16789380
TI  - Nurse practitioners deliver wound care.

PMID- 16789382
TI  - 'I'm a nurse too you know, nurses are great'!

PMID- 16789383
TI  - Innovation and enthusiasm: essential ingredients for transformation.

PMID- 16789381
TI  - It's only sunburn--a case study.

PMID- 16789384
TI  - Topic: clinical education for the future.

PMID- 16789385
TI  - Topic: Clinical education for the future.

PMID- 16789386
TI  - Developing an innovative undergraduate curriculum--responding to the 2002
      National Review of Nursing Education in Australia.
AB  - The Australian government responded to the recent global critical shortage of
      registered nurses by initiating a national review into nursing education. The 36
      recommendatons of the review report published in 2002 supported one or more of
      three strategies: building a sustainable workforce throuh partnership; maximising
      health outcomes through quaality education; and capacity building. The review
      drew extensively on the international research literature, invited submissions,
      previous reviews and commissioned research. This paper articulates the key
      features of a new innovative undergraduate nursing curriculum that incorporates
      several of the recommendations of the national review, specifically a new
      approach in delivery of the clinical component of the curriculum. The curriculum
      model emerged from a strategically planned partnership between a university and
      heath care providers committed to improving graduate outcomes and transition into
      professional practice. The curriculum was implemented in 2004 in a Faculty of
      Health Sciences that had not previously offered nursing programs. It is
      anticipated that the newly implemented undergraduate nursing program, modelled on
      a clinical schools partnership approach, will graduate registered nurses able to
      face the challenges of a rapidly changing health sector. The objective of this
      paper is to describe the key features of the program and share new insights that
      might challenge traditional curriculum approaches in undergraduate nursing.

PMID- 16789387
TI  - Clinical education delivery--a collaborative, shared governance model provides a
      framework for planning, implementation and evaluation.
AB  - Following a scheduled review of a university pre-registration Bachelor of Nursing
      program, a decision was taken to introduce a new model of clinical education
      delivery. Principles of collaboration, as used by other university nursing
      programs, were applied to the change management process. As the process of change
      progressed, a model incorporating collaboration and shared govemance emerged to
      address the challenge posed by multiple stakeholders from culturally different
      organisations and the genuine commitment by those stakeholders to share contol in
      the planning, implementation, and evaluation of the clinical education delivery
      model. Using a case study approach, this article demonstrates how the principles
      of collaboration and shared governance were combined to effectively manage change
      in the delivery of clinical education across several different organisations,
      aind provides an extended framework for collabortive change management involving
      multiple stakeholders.

PMID- 16789388
TI  - General practice nursing education in Australia.
AB  - The quality of care delivered by nurses working in Australian general practices
      rests on a strong foundation of nursing educatlon and training. A national study
      of nurses working in general practice was conducted using qualitative and
      quantitative research techniques to explore their role and educational needs.
      Results from this research suggest that education for general practice nurses is
      seen by nurses and General Practitioners to be largely non-formal in nature and
      is seen by GPs and nurses to be tailored towards general practice nursing needs.
      Such education is often available locally through general practice support
      organisations; is strongly focused on National Health Priority Areas and clinical
      care; and is more appropriate for registered rather than enrolled nurses. The
      educational opportunities currently available to support nursing in general
      practice are largely ad hoc and vary in relation to quality, appropriateness and
      accessibility. Nurses working in general practices in Australia need a system of
      ongoing training and education to support their responsibilities and foster the
      development of the position as a viable career option for nurses.

PMID- 16789389
TI  - Mentor evaluation of a year-long mentorship program: a quality improvement
      initiative.
AB  - This paper presents 23 mentors' perceptions of their role in a year-long
      mentorship program during the period 1999- 2002. The majority of mentors were
      clinical specialists, had bachelor degrees and over five years clinical
      experience. The mentorship program was informed by the Deming Cycle of Plan, Do,
      Check and Act. This quality improvement framework was used to evaluate the
      mentorship program from the mentors' perspective. Information was gathered
      through surveys and focus group discussions. Responses were analysed to identify
      three themes of 'Enhancing student learning outcomes', 'Time and resources' and
      'Personal and professional growth'. Mentors perceived their role as valuable in
      students' education and development. Despite concerns regarding adequate time and
      resources for an effective mentoring program, mentors acknowledged benefits to
      themselves in terms of personal and professional growth. Their vision and
      commitment to nursing was also evident in the perceived benefits of the program
      for the profession.

PMID- 16789390
TI  - Pain management skills of regional nurses caring for older people with dementia:
      a needs analysis.
AB  - An exploratory survey of the pain management education needs of 197 nurses
      working with older people with dementia was undertaken in a regional area of
      Queensland, Australia. The analysis indicated that nurses in this setting might
      not have the knowledge base to manage pain effectively; and that respondents have
      essentially negative perceptions of the availability and appropriateness of
      current pain management education programs. Consistent with non-metropolitan
      nurses generally, respondents expressed a preference for pain management
      education that had a significant face-to-face component allied with ongoing
      mentorship and support on completion of the program. The obstacles to attending
      such programs were also typical of the problems facing regional and rural nurses
      throughout Australia. These were identified as: inability to pay for courses;
      lack of information on what is available; distance to travel to education; and a
      perceived lack of employer support due to an inability to replace those staff
      attending education. Positive aspects include the degree to which participants
      were responsive and interested in dementia pain management and their access to,
      and acceptance of, non-medical pain therapies. The findings suggest a definite
      need for a dementia pain management program for aged care nurses, specifically
      tailored to their needs and to the constraints of the regional practice setting.

PMID- 16789392
TI  - Endo price hikes fail to materialize.

PMID- 16789391
TI  - Use your head before moving beds: precise planning aids vendor switch.

PMID- 16789396
TI  - Funding approves for faculty student loan program.

PMID- 16789398
TI  - Beyond a career: one nurse's call to care.

PMID- 16789399
TI  - The latest in treatments for incontinence in women.

PMID- 16789403
TI  - Familial dilated cardiomyopathy with troponin T K210del mutation.
AB  - BACKGROUND: It has been estimated that more than 30% of patients with idiopathic
      dilated cardiomyopathy have a familial form of the disease. The most frequent
      pattern of inheritance is autosomal dominant and several genes or loci have been
      implicated, coding for sarcomeric or cytoskeleton proteins. Most of the genotype
      phenotype correlations are still under study, but a particular mutation, K210del
      in the troponin T gene, has been identified in four different families with
      severe forms of DCM. The pathogenesis of this mutation has been inferred by
      functional studies but its transmission has not been demonstrated, perhaps due to
      the high mortality of the affected family members. The aim of this work was to
      investigate the prevalence of the K210del mutation in Portuguese and Mozambican
      families with dilated cardiomyopathy. METHODS: We evaluated 27 probands with
      familial DCM. Forty idiopathic (sporadic) DCM patients and 100 non-related
      healthy individuals were used as controls. Mutational analysis was performed by
      amplification of exon 13 of the troponin T gene by the polymerase chain reaction
      (PCR), determination of molecular weight of PCR products and further sequencing.
      RESULTS: The K210del mutation in the cardiac troponin T gene was identified in
      one of the DCM families which presented an aggressive form of the disease, with a
      high incidence of sudden death, and need for heart transplant at young age. One
      affected member had sustained left ventricular function recovery after diagnosis.
      CONCLUSIONS: These results reinforce previous work by others, indicating that
      this mutation is a bad prognostic factor in familial forms of DCM. The K210del
      mutation in the troponin T gene, like other mutations in the troponin complex,
      seems to be especially prevalent in families with rapidly progressive DCM or
      sudden cardiac death at young age.

PMID- 16789402
TI  - Anti-hypertensive drug utilization in Continental Portugal (1999-2004).
AB  - INTRODUCTION: The estimated prevalence of arterial hypertension (HT) in Portugal
      in 2003 was 43%, with only 28.8% of patients undergoing antihypertensive
      treatment having their blood pressure controlled. In the light of this fact, if
      HT is detected early and adequately controlled, there is great potential for
      reducing cardiovascular morbidity and mortality. OBJECTIVES: This study aimed to
      analyze patterns of antihypertensive drug utilization in Portugal at the regional
      and national level, to compare them with other countries, and to evaluate trends
      in certain indicators regarding use of these drugs. METHODS: Data on
      antihypertensive drug utilization refer to drugs prescribed and dispensed in the
      ambulatory population covered by the Portuguese national health service, from
      January 1, 1999 to June 30, 2004. Data were expressed in defined daily doses
      (DDD) per 1000 inhabitants per day (DID). RESULTS: Use of antihypertensives
      increased from 183 DID in the first half of 1999 to 256 DID in the first half of
      2004, an increase of 40%. Angiotensin-converting enzyme inhibitors were the most
      frequently prescribed drug class, being used by 31% of the study population,
      followed by diuretics (16%) and calcium channel blockers (14%). Angiotensin
      receptor blockers (ARBs) accounted for most of the growth in antihypertensive
      use, although they represent the most expensive therapeutic option. This pattern
      of use had a strong impact on antihypertensive drug expenditure, which increased
      60% over the study period. ARBs, plain or in combination formulations, accounted
      for 55% and 71% of the increase in utilization and expenditure respectively.
      DISCUSSION: From the standpoint of health gains, the significant rise in
      antihypertensive drug utilization represents a potentially favorable development
      in terms of increased numbers of patients undergoing drug treatment. Compared to
      other European countries, the data showed greater use of drugs that act on the
      renin-angiotensin system in Portugal and less use of diuretics and beta-blockers.
      Most national and international guidelines recommend diuretics as first-line
      agents in HT treatment. Considering that these drugs have the lowest daily
      treatment cost, a high, and increasing, rate of utilization would be expected,
      but this is not the case in Portugal. CONCLUSIONS: This study reveals not only
      significant differences in antihypertensive drug utilization at the regional
      level in Portugal but also a lack of adherence to national and international
      guidelines, and therefore more attention should be paid to their implementation
      in order to improve health gains.

PMID- 16789404
TI  - Relationship between ambulatory blood pressure monitoring values and future
      occurrence of ischemic cerebrovascular and coronary events in hypertensive
      patients.
AB  - OBJECTIVES: To evaluate in a prospective study the relationship between 24-hour
      ambulatory blood pressure monitoring (ABPM) values and the occurrence of nonfatal
      ischemic cerebrovascular and coronary events in treated hypertensive patients.
      METHODS: Out of 8780 ABPM recordings we identified 79 hypertensive patients (both
      genders) who suffered a first nonfatal ischemic event, either cerebrovascular
      (stroke or transient ischemic attack) (STR/TIA, n = 48) or coronary (myocardial
      infarction, angina or coronary bypass/PTCA) (COR, n = 31) and 223 control
      hypertensive patients (CTR) without any events during the same period who were
      fully matched (at the time of ABPM) for age, gender, antihypertensive therapy,
      presence of dyslipidemia or diabetes, and casual blood pressure (BP), in the
      proportion of 1 STR/TIA to 3 CTR and 1 COR to 6 CTR. Matched groups were compared
      for various ABPM parameters. RESULTS: On average, the time between ABPM and the
      occurrence of STR/TIA and COR events was respectively 32.4 (1 to 88) and 28.0 (1
      to 73) months. For similar values of matched variables significant differences (p
      < 0.05) were observed between STR/TIA vs. CTR in 24-hour systolic BP (147.4 +/-
      20.6 vs. 140.1 +/- 14.9 mmHg), daytime systolic BP (151.6 +/- 21.8 vs. 144.6 +/-
      15.2 mmHg) and nighttime systolic BP (138.5 +/- 21.2 vs. 130.9 +/- 16.0 mmHg),
      and between COR vs. CTR in 24-hour systolic BP (143.5 +/- 19.5 vs. 135.2 +/- 15.6
      mmHg), daytime systolic BP (146.3 +/- 20.5 vs. 139.6 +/- 15.9 mmHg) and nighttime
      systolic BP (138.1 +/- 19.7 vs. 126.2 +/- 16.4 mmHg), BP on rising (146.2 +/-
      31.7 vs. 133.6 +/- 19.9 mmHg) and blunted nighttime BP dipping (5.3 +/- 7.4 vs.
      9.60 +/- 6.0%). Versus CTR, STR/TIA showed a lower percentage of dippers (27.7
      vs. 44.4%) and a higher percentage of extreme dippers (10.6 vs. 6.3%), nondippers
      (48.9 vs. 41.7%) and inverted dippers (12.8 vs. 7.6%). Versus CTR, the COR group
      showed (p < 0.02) a lower percentage of dippers (21.9 vs. 46.8%) and extreme
      dippers (3.1 vs. 4.3%) and a higher percentage of nondippers (56.3 vs. 43.0%) and
      inverted dippers (18.8 vs. 5.9%). CONCLUSIONS: This prospective study in treated
      hypertensive patients shows that both high ABPM values and abnormal
      daytime/nighttime BP profiles are associated with later occurrence of ischemic
      cerebrovascular and coronary events independently of casual BP values and other
      cardiovascular risk factors. This reinforces the idea that ABPM is a powerful
      predictor of future cardiovascular events.

PMID- 16789405
TI  - Determinants of left ventricular systolic function recovery after an acute
      coronary syndrome.
AB  - INTRODUCTION: Ischemic heart disease is a major cause of heart failure in western
      societies. However, the factors that may influence left ventricular function
      (LVF) recovery after an acute coronary syndrome (ACS) are still unclear.
      OBJECTIVE: To identify variables that may influence LVF evolution one year after
      ACS. METHODS: 104 patients hospitalized with ACS between 7/1/2001 and 12/31/2002
      and with systolic dysfunction--defined as an echocardiographic ejection fraction
      (EF) < or = 45%--were randomly allocated to a planned coronary follow-up program
      (FUP) or a general cardiology clinic (GC); patients from both groups were also
      randomly referred to a structured cardiac rehabilitation program (CRP). EF was re
      assessed at one year. We compared differences between patients who recovered left
      ventricular function (EF > 45%; group 1) and those who did not (group 2).
      RESULTS: One year after discharge, 44.2% of the patients had recovered function.
      There were no significant differences between the groups in gender (77.7 vs.
      76.5% male), age (56 vs. 59 years), hypertension, diabetes, dyslipidemia, smoking
      habits or family history. A previous history of cardiovascular events was more
      frequent in group 2 (11.1% vs. 35.3%, p = 0.03). Cardiac catheterization was
      performed before discharge in 88.8% and 88.2% in groups 1 and 2 respectively (p =
      NS); no differences were found in coronary anatomy between the two groups.
      Angioplasty was performed in 54.2% in group 1 and 50% in group 2 (p = NS). There
      were no differences in the use of angiotensin-converting enzyme inhibitors (83.3%
      vs. 87.5%), beta-blockers (87.5% vs. 87.5%), nitrates (37.5% vs. 33.3%), aspirin
      (95.8% vs. 95.8%), statins (79.1% vs. 75%) or diuretics (20.8% vs. 45.8%). There
      was no significant difference in LVF recovery between patients randomized to FUP
      or GC (38.5% vs. 54.5%). 87.5% of patients who completed the CRP had normal EF at
      one year compared to 32.7% of patients not referred to the program (p = 0.009).
      Although EF improved in both groups, this improvement was greater in patients who
      completed a CRP (EF 8% vs. 5%, p = 0.003). CONCLUSION: A previous cardiovascular
      event and completion of a CRP were the only variables that influenced LVF
      recovery. Thus, enrollment in a CRP, in addition to standard therapy, could be an
      important therapeutic measure in patients with systolic dysfunction after ACS;
      our data suggest that these programs should be more widely used.

PMID- 16789406
TI  - Hypoplastic left heart syndrome with in utero closed foramen ovale: case report.
AB  - We report a case of a newborn with a prenatal diagnosis of hypoplastic left heart
      syndrome (HLHS), referred at 37 weeks of gestation. The fetal echocardiogram had
      shown classic morphologic aspects of HLHS with patent mitral valve and aortic
      valve atresia. The atrial septum was thickened and the foramen ovale (FO)
      appeared to be patent. It was a normal full-term delivery, with birth weight of
      2540 g. Orotracheal intubation and mechanical ventilation were immediately
      necessary, as well as intravenous prostaglandin, due to clinical deterioration.
      Transthoracic echocardiography performed in the first hour of life confirmed the
      diagnosis, but doubts were raised about the patency of the FO. Cardiac
      catheterization was performed and Rashkind balloon atrial septostomy was
      attempted, without success. The baby died and pathologic examination revealed
      HLHS with intact atrial septum, dilated coronary sinus and pulmonary
      lymphangiectasia. In this case, the dilated coronary sinus led to a mistaken
      prenatal diagnosis of FO patency with left-to-right shunt.

PMID- 16789407
TI  - Analgesia, sedation and neuromuscular blockade in mechanically ventilated cardiac
      intensive care unit patients. Part III--Neuromuscular blockade.
AB  - This article reviews relevant clinical issues regarding sedation, analgesia and
      neuromuscular blockade in the cardiac intensive care unit, including monitoring
      tools and available therapeutic options. The pathophysiologic implications of
      pain, agitation, anxiety and delirium in the ventilated patient are also
      discussed. Although guidelines for sedation, analgesia and neuromuscular blocking
      drugs in critical care have recently been published, there is great variability
      in clinical practice. The complexity of the environment and associated
      pathologies makes it difficult to implement universally applicable therapeutic
      regimens. Knowledge of pharmacologic mechanisms is an important tool in the
      development of dynamic protocols adapted to each unit. Strategies that include
      monitoring resources are essential for the optimization of sedation, analgesia
      and neuromuscular blockade.

PMID- 16789408
TI  - National Registry on Cardiac Electrophysiology--2004.

PMID- 16789409
TI  - Double aortic arch.

PMID- 16789410
TI  - Sinus venosus atrial septal defect in an adult, diagnosed by transesophageal
      echocardiography.

PMID- 16789411
TI  - [The process leading up to the preparation of a 50-year-history of the Japanese
      Society of Hygienics].

PMID- 16789412
TI  - [Topics at the meetings of the Japanese Society of Hygienics during the past 25
      years].

PMID- 16789413
TI  - Immunohistochemical study of the association between the progression of
      pancreatic ductal lesions and the expression of MUC1, MUC2, MUC5AC, and E
      cadherin.
AB  - Pancreatic cancer is a highly malignant tumor. In this study, we examined the
      association between the expression of MUC1, MUC2, MUC5AC, and E-cadherin, and the
      pathological changes from normal pancreatic tissue to invasive ductal
      carcinoma(IDC). Since MUC1 is known to be involved in the inhibition of E
      cadherin, we also examined the association between MUC1 and E-cadherin. Five
      normal pancreatic tissues, 6 chronic pancreatitis tissues, 20 pancreatic
      intraepithelial neoplasia (PanIN) tissues, and 24 IDC tissues were fixed in
      formalin, embedded in paraffin, and sections were immunostained. MUC1 was
      positive in nonneoplastic tissues, PanIN-3, and IDC. MUC2 was negative in almost
      all tissues. MUC5AC was positive in neoplastic tissues. E-cadherin was positive
      in almost all tissues. Changes in MUC1 staining were observed in PanIN-3 and IDC,
      and E-cadherin staining was seen in neoplastic tissues. MUC1 was more diffusely
      positive in lymph node metastasis-positive cases. The expression of MUC1 and
      MUC5AC is associated with the progression of PanIN. MUC1 may promote the
      inhibition of E-cadherin. The results also suggest that MUC1 is useful as a
      prognostic marker.

PMID- 16789414
TI  - [The relationship of autonomic functional disturbance and atherosclerosis in type
      2 diabetes].
AB  - The aim of the study was to assess the relationship between the autonomic nerve
      disturbance and atherosclerotic changes in patients with type 2 diabetes. Aortic
      distensibility and max carotid intima-media thickness (Max IMT) were evaluated
      using brachial ankle pulse wave velocity (PWV) and high-resolution B-mode
      ultrasonography, respectively, in 135 patients (69 men, 66 women, 57 +/- 16
      years) with type 2 diabetes. The autonomic neuropathy was evaluated using
      coefficient of variation of the RR interval (CV(R-R)) of electrocardiograms
      recorded at rest in a supine position. There was a significant negative
      correlation between CV(R-R)and Max IMT (r= -0.488, p< 0001). There were also
      significant negative correlations between CVR-(R a)nd the left and the right
      PWV(r=0.518, p<0.001; r=0.551, p<0.001, respectively). Patients with normal Max
      IMT, but decreased CVR-R, had a high PWV compared to patients with normal Max IMT
      and normal CVR-(R. )Therefore, decreased CVR-(R i)n type 2 diabetic patients may
      reflect atherosclerotic changes. Thus, the measurement of CVR-(R i)s a simple and
      quantitative test for assessing atherosclerotic as well as neuropathic
      complications in diabetic patients.

PMID- 16789415
TI  - [Effects of magnetic resonance imaging on neutrophil functions].
AB  - We evaluated the effects of magnetic resonance (MR) imaging on human neutrophil
      functions. In addition of the counting of leukocyte and neutrophil number,
      expression levels of adhesion molecules on neutrophil surface such as CD11b and L
      selectin, and reactive oxygen species (ROS) production were determined by means
      of flowcytometry. Complete blood count did not show any difference between before
      and after MR imaging in five normal healthy volunteers. The levels of cell
      surface adhesion molecules were not altered in both in vivo MR imaging (n=5) and
      in vitro MR exposure experiments (n=13). Moreover, the levels of ROS production
      were also not affected by in vivo MR imaging. On the other hand, neutrophils
      exposed to MR in vitro exhibited significant increase in ROS production after
      stimulation with fMLP combined with lipopolysaccharide, although no increase was
      observed with PMA stimulation. Actually, there have been no reports describing
      the complication relating to hyper-neutrophil function as far as we could search,
      but it might be necessary to evaluate the biological effects of MR imaging
      especially under the pathologic circumstances that induce neutrophil activation.

PMID- 16789416
TI  - [Examination of the increased speed of detection of HER-2/neu gene amplification
      in breast cancer by fluorescence in situ hybridization (FISH) using image
      analysis software].
AB  - The time required to count signals in the detection of HER-2/neu gene
      amplification in breast cancer by fluorescence in situ hybridization (FISH) has
      been a problem. To assess whether the amount of time necessary for counting could
      be reduced, image analysis using computer software (Win ROOF) was tested. Five
      photographs from each FISH sample were arranged into ten composite photographs.
      All ten composite photographs were necessary when using the conventional method
      of manual counting. However, using only four of the composite photographs and the
      image analysis method, the 60 necessary nucleus numbers could be measured, and a
      constant ratio of HER-2/neu / CEP 17 was obtained. In all 58 samples used, in the
      presence or absence of HER-2/neu gene amplification, there was agreement in
      counts between the conventional and image analysis methods, and a good
      correlation of r=0.961 (p<0.001) was obtained. Using the image analysis method,
      the necessary scoring time was reduced, particularly when the HER-2/neu gene had
      been amplified, where it was completed in about 1/4 of the time normally
      required. These results indicate that this image analysis method can be applied
      when using FISH in other areas of research, and may increase the speed of
      examination.

PMID- 16789417
TI  - [Magnetocardiographic diagnosis for myocardial ischemia and arrhythmias].
AB  - Magnetocardiography (MCG) is a non-invasive and non-contact mapping technique to
      analyze cardiac electromagnetic activities. The SQUID (superconducting quantum
      interference device) system has made it possible to detect very weak cardiac
      magnetic signals noninvasively. In electrocardiography (ECG), the conductivity of
      electric current varies according to body composition, while in MCG, conductivity
      of magnetic field is constant regardless of body composition. Moreover, as the
      magnetic field detected in MCG originates not from the cardiac 'volume current'
      as in ECG, but from the cardiac 'primary current', the cardiac electromagnetic
      information of the MCG is minimally distorted. Furthermore, ECG is a record of a
      potential difference, so it gives only a relative value, while magnetic field
      strength is an absolute value. Therefore, MCG is expected to be more sensitive to
      minute electromagnetic abnormalities of heart disease than ECG. In this article,
      we discuss the usefulness of MCG in diagnosing ischemic heart diseases and
      arrhythmias.

PMID- 16789418
TI  - [Fetal magnetocardiography].
AB  - The electrical activities of the heart causes weak changes of the magnetic field,
      which can be recorded as magnetocardiogram (MCG). Fetal cardiac magnetic activity
      is measured in the order of less than 10 pT. An advance of the novel technology
      of a superconducting quantum interference device enabled the first recording of
      fetal MCG (FMCG) in 1974. In Japan, FMCG instrument (MC6400, Hitachi High
      Technologies Ltd) was approved as a diagnostic tool by Japanese Government in
      2003 owing to the cooperative studies of Tsukuba University, National
      Cardiovascular Center and Hitachi Ltd. FMCG offers similar information to a fetal
      electrocardiogram, which is difficult to be recorded because the fetal skin is
      covered with fatty caseous vernix of weak electrical conductivity in the second
      and third trimester of pregnancy. Magnetic flux can pass through the fat layer,
      and thus FMCG can measure the electrical activity of the fetal heart. Besides
      FMCG has far higher resolutions in time domain than echocardiography does. The
      amplitude of FMCG signals depends on the size of fetal heart and the distance
      between the sensors and the fetal heart. The amplitudes of the QRS, P and T waves
      increases with gestational age. Since the amplitudes of P and T waves are often
      weak, averaging of FMCG signals is needed to improve the signal-to-noise ratio.
      Current-arrow map is a useful mapping technique even in FMCG. FMCG has been
      applied in the prenatal diagnosis of fetal arrhythmias such as bradyarrhythmia
      (atrioventricular block, long QT syndrome, etc), tachyarrhythmia
      (supraventricular tachycardia, atrial flutter, atrial fibrillation and WPW
      syndrome, etc) and extrasystoles. Fetal cardiomegaly with myocardial
      abnormalities can be also diagnosed by FMCG. Applications of FMCG for fetal heart
      rate monitoring using beat-to-beat variability have been also studied to obtain
      better information on fetal well-beings.

PMID- 16789419
TI  - [Validation of the ISO 15189 trial assessment results of clinical laboratories-
      effects of accreditation and interpretation of ISO 15189].
AB  - Japanese Committee for Clinical Laboratory Standards (JCCLS) and the Japan
      Accreditation Board for Conformity Assessment (JAB) have developed an
      accreditation program for clinical laboratories using ISO 15189 in Japan. On
      October 1, 2004, twelve clinical laboratories applied for trial accreditation
      assessment. Seven laboratories were selected, including a university hospital
      laboratory, two other hospital-based laboratories, three large private clinical
      laboratories and an other private clinical laboratory. JAB had given a one week
      training course to the candidate technical assessors who were nominated from the
      Japanese Society of Laboratory Medicine (JSLM) and the Japanese Association of
      Medical Technologists (JAMT), and candidate system assessors who were nominated
      from JAB. Thirty-five members had successfully passed the examination. During the
      period from November 2004 to May 2005, five laboratories were visited for
      assessment by four to six assessors for two or three days. Final assessment
      reports were discussed by the program developing committee for the validation of
      the accreditation program. The conclusions were that the program did not have any
      critical problems, but the assessment visit would have been more efficient if JAB
      published an easily understandable guidance document on ISO 15189, and had some
      training courses for laboratories in Japan in order to understand ISO 15189 more
      deeply. In addition, JAB should develop a more simplified checklist, mainly
      describing the important requirements. JAB formally started the clinical
      laboratory accreditation scheme from August 1, 2005 and five laboratories were
      accredited by the newly started accreditation committee on August 31, 2005, and
      four laboratories were additionally accredited on November 28, 2005. The most
      difficult clauses in ISO 15189:2003 were 5.6.2 and 5.6.3 on uncertainty and
      traceability, and 5.7.1 on post-examination procedures. Some difficult clauses to
      understand in the International Standard were discussed.

PMID- 16789420
TI  - [Transthyretin-its function and pathogenesis].
AB  - Transthyretin (TTR) is a transport protein for retinol-binding protein and
      thyroxin, and works as a rapid turnover protein. Recently, it has been used as a
      nutrition assessment protein in the assessment of the acute phase nutritional
      status in various diseases because it contains four tryptophans in the tetramer
      of the protein and its plasma half life is 1.9 days. However, the wild-type
      protein and its mutated form become a precursor protein of amyloid fibrils in
      senile systemic amyloidosis (SSA) and familial amyloidotic polyneuropathy(FAP),
      respectively. Recent biochemical and pathological studies revealed that
      instability of the terameric form of TTR by mutation and post-translational
      modifications leads to amyloid formation in the tissues of SSA and FAP. In the
      process of TTR amyloid formation, misfolding of TTR, the trigger of amyloid
      formation, is also induced. For these amyloid formation mechanisms, Cr3+
      administration, BSB(FSB) therapy, gene therapy, and antibody therapy are now on
      going therapeutic projects for FAP and SSA.

PMID- 16789421
TI  - [Alzheimer's disease as brain amyloidosis: diagnosis using cerebrospinal fluid
      abeta and tau].
AB  - Recent progress in the treatment for Alzheimer's disease (AD) emphasizes the need
      for early diagnosis of AD. It is also becoming a noteworthy issue to determine if
      a patient with mild cognitive impairment (MCI) has incipient AD. Three
      cerebrospinal fluid (CSF) biomarkers: beta-amyloid42 (Abeta42), total tau (t-tau)
      and phosphorylated tau (p-tau) have been evaluated in numerous scientific papers.
      Summary of these large-scale studies suggested that measurements of Abeta40/42
      and t-tau in CSF are clinically useful for the diagnosis of AD, especially when
      they are combined. Studies showed that measurement of p-tau improves the early
      and differential diagnosis of AD. They are also useful markers to identify
      incipient AD in MCI cases. Early diagnosis of AD using these assays is an
      evidence-based biomarker that can be the basis for treatment with drugs aimed at
      targeting the degenerating processes of AD.

PMID- 16789422
TI  - [Serum amyloid A (SAA)--pathogenicity and implication of appearance in plasma].
AB  - Serum amyloid A, SAA, is a plasma precursor of reactive amyloid fibrils and a
      sensitive acute phase reactant. The prolonged high production of SAA in chronic
      inflammation is the most essential for amyloidogenesis. In addition, impaired
      catabolism of SAA and SAA polymorphism may enhance disease development. SAA1
      polymorphism affects the plasma concentration of SAA, probably because of
      differences in plasma clearance. Interestingly, amyloidogenic polymorphism
      (SAA1.3) does not show a high plasma SAA concentration. The true significance of
      SAA polymorphism in amyloidogenesis and physiological function is under
      investigation. Although SAA is produced primarily in the liver, attention has
      recently focused on extra-hepatic production and its physiological significance.
      In non-inflammatory conditions, the extrahepatic sites may constantly produce SAA
      while the expression may be suppressed in the liver. Therefore, it is possible
      that some parts of SAA in non-inflamed plasma are derived from extrahepatic sites
      such as adipose tissues and cells in the vascular wall.

PMID- 16789423
TI  - [Histopathological diagnosis of amyloidosis].
AB  - For the diagnosis of amyloidosis, histological evidence of amyloid deposition is
      essential. Histologically, an amyloid deposit is stained orange red with Congo
      red and shows green birefringence under polarized light. When amyloidosis is
      clinically suspected, endoscopic biopsy of the stomach, duodenum or colon, or
      aspiration biopsy of abdominal fat is usually performed. If clinicians suspect
      amyloidosis, they should advise pathologists. Identification of the chemical type
      of amyloid is necessary with respect to treatment and prognosis.
      Immunohistochemical examination of amyloid in formalin-fixed, paraffin-embedded
      sections is simple to perform in most pathological laboratories. In Japan, almost
      all cases of systemic amyloidosis are classified as AL, AA, ATTR or Abeta2M
      amyloidosis, so the use of anti-immunoglobulin light chain, anti-amyloid A, anti
      transthyretin and anti-beta2 microglobulin antibody is recommended for the
      classification of systemic amyloidosis. Formic acid pretreatment, which is often
      used for immunohistochemical detection of amyloidosis, is useful and easy for
      antigen retrieval. Amyloid deposits of AL amyloidosis are sometimes not
      immunostained well with commercial anti-immunoglobulin light chain antibody.
      Previously, we generated polyclonal antibodies against synthetic peptides
      corresponding to positions 118-134 of immunoglobulin lambda light chain and
      positions 116-133 of immunoglobulin kappa light chain. These antibodies are very
      useful for detecting AL amyloidosis because they react with amyloid deposits on
      formalin-fixed, paraffin-embedded specimens in almost all AL amyloidosis cases.
      Exact diagnosis and typing of amyloidosis are necessary for therapy.

PMID- 16789424
TI  - [Noninvasive blood glucose monitoring: new technology using metabolic heat
      conformation method].
AB  - Self-monitoring of blood glucose has become an essential aspect of management of
      patients with diabetes mellitus. Although several approaches for noninvasive
      blood glucose monitoring(NIGM) have been proposed including near infrared
      spectrophotometry. Body heat generated by glucose oxidation is based on the
      subtle balance of capillary glucose and oxygen supply to the cells. Hence, the
      blood glucose can be estimated by measuring the body heat and the oxygen supply.
      Development of the metabolic heat conformation (MHC) method consists of a sensor
      pickup and a calibration model. The calibration model incorporates mathematical
      procedures to process signals from the sensor pickup to final glucose value. The
      patients group was classified into clusters (calibration functions). Each subject
      patient was assigned to one of calibration functions. The assigned calibration
      function for the patient was later used for calculating the glucose values.
      Regression analysis involving 127 data points at random timing (109 data points
      from diabetic patients, 18 data points from non-diabetic patients) ranging
      54mg/dl to 405mg/dl by the non-invasive method against the hexokinase photometric
      method for plasma as a reference method was performed. The correlation
      coefficient (r) was 0.91. Repeatability of the non-invasive method was measured
      for healthy fasting persons. The standard deviations were ranged from 5 to 6mg/dl
      around the concentration of 100mg/dl. These data provide preliminary evidence
      that the MHC method can be used to estimate blood glucose concentrations non
      invasively.

PMID- 16789425
TI  - Quantitative structure-activity relationships (QSars) in CYP3A4 inhibitors: the
      importance of lipophilic character and hydrogen bonding.
AB  - The results of Quantitative Structure-Activity Relationship (QSAR) analyses on
      three series of CYP3A4 inhibitors are reported for enzyme inhibition expressed as
      Ki values. These include a small series of structurally related statins and two
      larger groupings of structurally diverse compounds, some of which display
      competitive inhibition of CYP3A4 whereas others act via heme iron ligation. In
      all cases, however, it is apparent that there are lipophilicity relationships
      associated with CYP3A4 inhibitory activity in the total of 46 compounds
      investigated. This is evidenced by linear correlations between inhibition of
      CYP3A4 and the octanol-water partition coefficient (P value) when expressed
      logarithmically (ie., log P). In the case of the statins, however, the
      distribution coefficient (D) at pH 7 is used due to the effect of compound
      ionization. Conversion of equilibrium constants (ie. Ki and P) to the
      corresponding free energy changes (deltaG values) facilitates exploration of the
      likely intermolecular forces of interaction between the inhibitors and the active
      site region of CYP3A4. In this respect, there appears to be good agreement
      between QSAR analyses and molecular modelling of the CYP3A4 enzyme itself, and
      both are consistent with the known mechanisms of inhibition displayed.

PMID- 16789426
TI  - Inhibition of acetylcholinesterase by two arylderivatives: 3a-Acetoxy-5H-pyrrolo
      (1,2-a) (3, 1)benzoxazin- 1,5-(3aH)-dione and cis-N-p-Acetoxy-phenylisomaleimide.
AB  - Two arylderivatives, 3a-Acetoxy-5H-pyrrolo(1,2-a) (3,1)benzoxazin-1,5-(3aH)-dione
      3 and cis-N-p-Acetoxy-phenylisomaleimide 4, were synthesized from anthranilic
      acid and para-aminophenol, respectively. The inhibitory effects of these
      compounds on acetylcholinesterase (AChE) activity were evaluated in vitro as well
      as by docking simulations. Both compounds showed inhibition of AChE activity (Ki
      = 4.72 +/- 2.3 microM for 3 and 3.6 +/- 1.8 microM for 4) in in vitro studies.
      Moreover, they behaved as irreversible inhibitors and made pi-pi interaction with
      W84 and hydrogen bonded with S200 and Y337 according to experimental data and
      docking calculations. The docking calculations showed deltaG bind (kcal/mol) of -
      9.22 for 3 and - 8.58 for 4. These two compounds that can be use as leads for a
      new family of anti-Alzheimer disease drugs.

PMID- 16789427
TI  - Synthesis and anti-inflammatory activity of some selected aminothiophene analogs.
AB  - Some 2-aminothiophene analogs 1-6 were synthesized and characterized. Among the
      tested compounds, compound 1 (IC50 121.47 microM) exhibited highest while the
      compound 5 showed least anti-inflammatory potential (IC50 422 microM).

PMID- 16789428
TI  - Semisynthesis and cytotoxic activities of andrographolide analogues.
AB  - Andrographolide 1, a diterpenoid lactone of the plant Andrographis paniculata,
      known to possess antitumour activity in in vitro and in vivo breast cancer models
      was subjected to semisynthesis leading to the preparation of a number of novel
      compounds. These compounds exhibited in vitro antitumour activity with moderate
      to excellent growth inhibition against MCF-7 (breast) and HCT-116 (colon) cancer
      cells. Compounds 3,19-(2-chlorobenzylidene)andrographolide(5), 3,19-(3
      chlorobenzylidene)andrographolide(6), 3,19-(3-fluorobenzylidene)
      andrographolide(7), 3,19-(4-fluorobenzylidene)andrographolide(8), 3,19-(2
      fluorobenzylidene)andrographolide(10), 3,19-(2-chloro-5
      nitrobenzylidene)andrographolide (21), 3,19-(4
      chlorobenzylidene)andrographolide(30) and 3,19-(2-chloro-4-fluorobenzylidene)
      andrographolide(31) were also screened against 60 NCI (National Cancer Institute,
      USA) human tumour cell lines derived from nine cancer cell types.

PMID- 16789429
TI  - Coumarin Schiff-bases: as antioxidant and possibly anti-inflammatory agents.
AB  - Coumarin Schiff-bases (CSB) possessing different substituents on the 4-methyl-2
      substituted phenyl imino-2H-chromene-7-ol molecule were evaluated for their in
      vitro antioxidant and plausible anti-inflammatory potential. The antioxidant
      studies of selected CSB were carried out by determining their reducing power, OH*
      radical scavenging activity, scavenging of stable 2,2-diphenyl-l-picrylhydrazine
      (DPPH*) radical and inhibition of the polyphenol oxidase (PPO) enzyme. The
      assessment of possible anti-inflammatory potential was performed by trypsin
      inhibition assay and inhibition of beta-glucuronidase. All the CSBs under study
      showed significant reducing effects. The majority of the tested CSB were found to
      be effective scavengers of DPPH* radical with moderate to low OH* scavenging
      ability and significantly inhibited the activity of PPO. With few exceptions,
      results from the inhibition assay of trypsin and beta-glucuronidase were not
      encouraging, however they may be helpful in defining structure-activity
      relationships in further optimization of the lead molecules.

PMID- 16789430
TI  - Berberine potently inhibits protein tyrosine phosphatase 1B: investigation by
      docking simulation and experimental validation.
AB  - Berberine was investigated as an inhibitor of human protein tyrosine phosphatase
      1B (h-PTP 1B) in an attempt to explain its anti-hyperglycemic activitiy. The
      investigation included simulated docking experiments to fit berberine within the
      binding pocket of h-PTP 1B. Berberine was found to readily fit within the binding
      pocket of h-PTP 1B in a low energy orientation characterized with optimal
      electrostatic attractive interactions bridging the isoquinolinium positively
      charged nitrogen atom of berberine and the negatively charged acidic residue of
      ASP 48 of h-PTP 1B. Experimentally, berberine was found to potently competitively
      inhibit recombinant h-PTP 1B in vitro (Ki value = 91.3 nM). Our findings strongly
      suggest that h-PTP 1B inhibition is at least one of the reasons for the reported
      anti-hyperglycemic activities of berberine.

PMID- 16789431
TI  - Antibacterial, antifungal and cytotoxic properties of some sulfonamide-derived
      chromones.
AB  - A series of antibacterial and antifungal sulfonamide (sulfanilamide,
      sulfaguanidine, sulfamethaxozole, 4-aminoethylbenzene-sulfonamide and 4-amino-6
      trifluoromethyl-benzene-1,3-disulfonamide) derived chromones, previously reported
      as inhibitors of carbonic anhydrase, have been screened for in-vitro
      antibacterial activity against four Gram-negative (Escherichia coli, Pseudomonas
      aeruginosa, Salmonella typhi and Shigella flexener) and two Gram-positive
      (Bacillus subtilis and Staphylococcus aureus) bacterial strains, and for in-vitro
      antifungal activity against Trichophyton longifusus, Candida albicans,
      Aspergillus flavus, Microsporum canis, Fusarium solani, Candida glaberata. All
      compounds (1)-(5) showed significant antibacterial activity against all four Gram
      negative species and both Gram-positive species. However, three of them, (1), (4)
      and (5), were found to be comparatively much more active compared to (2) and (3).
      Of these, (5) was found to be the most active one. For antifungal activity,
      generally compounds (1) and (2) showed significant activity against more than
      three strains whereas (3)-(5) also showed significant activity against varied
      fungal strains. In the brine shrimp bioassay for in-vitro cytotoxic properties,
      only two compounds, (4) and (5) displayed potent cytotoxic activity, LD50 = 2.732
      x 10(-4)M) and LD50 = 2.290 x 10(-4)M) respectively, against Artemia salina.

PMID- 16789432
TI  - Novel N-acyl dehydroalanine derivatives as antioxidants: studies on rat liver
      lipid peroxidation levels and DPPH free radical scavenging activity.
AB  - Oxidative stress has been implicated in the development of many neurodegenerative
      diseases such as Parkinson and Alzhemier's disease and is also responsible for
      aging, artherosclerosis, rheumatoid arthritis and carcinogenesis. Olefins such as
      dehydroalanines have been shown to inactivate free radicals by forming stabilized
      free radical adducts. Among these molecules N-acyl dehydroalanines react with and
      scavenge oxygen and hydroxyl radicals. This study describes the synthesis,
      characterization and in vitro effects on rat liver lipid peroxidation levels, and
      DPPH free radical scavenging activities of some N-acyl dehydroalanine
      derivatives. Compounds c, f and j slightly scavenged the level of DPPH radical at
      10(-3) M concentration by about 27, 46, and 56%, respectively while compounds a,
      d, e, f, g, h showed a strong inhibitory effect on lipid peroxidation at 10(-3)M
      and 10(-4)M concentrations and inhibition was in the range of 76-90%. The
      possible antioxidant mechanism of the compounds was discussed.

PMID- 16789433
TI  - Antibacterial cobalt (II), copper (II), nickel (II) and zinc (II) complexes of
      mercaptothiadiazole--derived furanyl, thienyl, pyrrolyl, salicylyl and pyridinyl
      Schiff bases.
AB  - A series of Co (II), Cu (II), Ni (II) and Zn (II) complexes of
      mercaptothiadiazole-derived furanyl, thienyl, pyrrorlyl, salicylyl and pyridinyl
      Schiff bases were synthesized, characterized and screened for their in vitro
      antibacterial activity against four Gram-negative, Escherichia coli, Pseudomonas
      aeruginosa, Salmonella typhi and Shigella fexneri, and two Gram-positive;
      Bacillus subtilis and Staphylococcus aureous bacterial strains. The results of
      these studies show the metal complexes to be more antibacterial as compared to
      the prepared un-complexed Schiff bases.

PMID- 16789434
TI  - Bactericidal activity of different oxovanadium(IV) complexes with Schiff bases
      and application of chelation theory.
AB  - Oxovanadium(IV) complexes have been synthesized and characterized the general
      composition [VOL(A)], where H2L = salicylidene-o-aminothiophenol A1 =
      bis(benzylidene)ethylenediamine, A2 = bis(acetophenone)ethylenediamine, A3 = 2,2'
      bipyridylamine, A4 = bis(benzylidene) - 1,8-diaminonaphthalene, A5 = thiophene-o
      carboxaldeneaniline and A6 = thiophene-o-carboxaldene-p-anisidine. Spectral
      studies indicate that the oxovanadium(IV) complexes assume a six-coordinate
      octahedral geometry. The antibacterial activities of the complexes against
      Salmonella typhi, Escherichia coli and Serratia mercescens are higher as compared
      to the free ligands, vanadyl sulphate, and the control (DMSO) but of moderate
      activity as compared to the standard drug (tetracycline).

PMID- 16789435
TI  - Antimicrobial activity studies on some piperidine and pyrrolidine substituted
      halogenobenzene derivatives.
AB  - The in vitro antibacterial and antifungal activities of the compounds synthesised
      from some 1,2,3,5-tetrahalogeno benzenes in presence of sodium piperidide and
      sodium pyrrolidide (2,6-dipiperidino-1,4-dihalogenobenzenes; 2,6-dipyrrolidino
      1,4-dibromobenzene; 2,4,6-tripyrrolidino chlorobenzene; and 1,3-dipyrrolidino
      benzene) were investigated. The in vitro antimicrobial activities were screened
      against the standard strains: Staphylococcus aureus ATCC 25923 and Bacillus
      subtilis ATCC 6633 as Gram positive, Yersinia enterocolitica ATCC 1501,
      Escherichia coli ATCC 11230 and Klebsiella pneumoniae as Gram negative, and
      Candida albicans as yeast-like fungus. Compounds (3, 5, 6, 7) inhibited the
      growth of all the test strains at MIC values of 32-512 microg/ml. None of the
      four compounds (1, 2,4,8) studied showed antimicrobial activity against any of
      the test strains within the MIC range 0.25-512 micro/ml.

PMID- 16789436
TI  - Tamarix gallica ameliorates thioacetamide-induced hepatic oxidative stress and
      hyperproliferative response in Wistar rats.
AB  - Tamarix gallica, a hepatic stimulant and tonic, was examined for its ability to
      inhibit thioacetamide (TAA)-induced hepatic oxidative stress, toxicity and early
      tumor promotion response in male Wistar rats. TAA (6.6 mmol/kg body wt. i.p)
      enhanced lipid peroxidation, hydrogen peroxide content, glutathione S-transferase
      and xanthine oxidase with reduction in the activities of hepatic antioxidant
      enzymes viz., glutathione peroxidase, superoxide dismutase and caused depletion
      in the level of hepatic glutathione content. A marked increase in liver damage
      markers was also observed. TAA treatment also enhanced tumor promotion markers,
      ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into
      hepatic DNA. Pretreatment of rats orally with Tamarix gallica extract (25 and 50
      mg/kg body weight) prevented TAA-promoted oxidative stress and toxicity.
      Prophylaxis with Tamarix gallica significantly reduced the susceptibility of the
      hepatic microsomal membrane for iron-ascorbate induced lipid peroxidation, H2O2
      content, glutathione S-transferase and xanthine oxidase activities. There was
      also reversal of the elevated levels of liver marker parameters and tumor
      promotion markers. Our data suggests that Tamarix gallica is a potent
      chemopreventive agent and may suppress TAA-mediated hepatic oxidative stress,
      toxicity, and tumor promotion response in rats.

PMID- 16789437
TI  - Effects of cadmium and zinc ions on purified lamb kidney cortex glucose-6
      phosphate dehydrogenase activity.
AB  - Glucose-6-phosphate dehydrogenase (G-6-PD) is the first enzyme in the pentose
      phosphate pathway. Cadmium is a toxic heavy metal that inhibits several enzymes.
      Zinc is an essential metal but overdoses of zinc have toxic effects on enzyme
      activities. In this study G-6-PD from lamb kidney cortex was competitively
      inhibited by zinc both with respect to glucose-6-phosphate (G-6-P) and NADP+ with
      Ki values of 1.066 +/- 0.106 and 0.111 +/- 0.007 mM respectively whereas cadmium
      was a non-competitive inhibitor with respect to both G-6-P and NADP+ Ki values of
      2.028 +/- 0.175 and 2.044 +/- 0.289 mM respectively.

PMID- 16789438
TI  - In vitro effects of some drugs on catalase purified from human skin.
AB  - Catalase enzyme (H202: oxidoreductase; E.C. 1.11.1.6) was purified from human
      skin homogenate using ammonium sulfate precipitation and DEAE-Sephadex A50 ion
      exchange chromatography at 4 degrees C and some characteristics of the enzyme
      were investigated. The human skin enzyme, having a specific activity of 1354.5
      EU/mg proteins was purified with a yield of 43.13% and 1110-fold. Sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed a single band for
      the enzyme. Inhibition by piroxicam, ketoprofen, diclofenac sodium,
      sulfamethoxazole and nidazole occurred with I50 values of 0.414, 1.29, 1.8, 3.83,
      and 8.64 mM, respectively.

PMID- 16789439
TI  - Effects of some drugs on purified human erythrocyte CuZnSOD and in vitro
      inhibitiory effect of 5-fluorouracil on leukocyte total SOD activity.
AB  - The inhibition and activation effects of some drugs on the activities of
      superoxide dismutase enzymes (SOD) in human erythrocyte and leukocyte cells was
      investigated. Firstly, CuZnSOD enzyme was purified 837-fold and 12% efficiency
      from human erythrocytes by ethanol-chloroform treatment to remove hemoglobin and
      then ion exchange chromatography (DEAE-Sepharose) and copper chelate affinity
      chromatography techniques. Inhibition or activation effects of fourteen drugs on
      CuZnSOD was investigated. None of the studied drugs except for 5-fluorouracil
      showed any effects on the enzyme. 5-fluorouracil showed activation effects on
      CuZnSOD at 3.33mg/ml and 4mg/ml concentrations with 33% and 32% activation,
      respectively. Leukocytes were isolated from healthy human blood, lysed in liquid
      nitrogen and the effect of 5-fluorouracil on the lysate SOD activity
      investigated. 5-Fluorouracil showed inhibition effects on total SOD activity of
      human leukocytes at 2 mg/ml and 4 mg/ml concentrations with 42% and 62%
      inhibition, respectively.

PMID- 16789440
TI  - Synthesis and evaluation of in vitro antioxidant capacities of some benzimidazole
      derivatives.
AB  - New, except 1d, melatonin analogue benzimidazole derivatives were synthesized and
      characterized in the present study. The potential role of melatonin as an
      antioxidant by scavenging and detoxifying ROS raised the possibility that
      compounds that are analogous to melatonin can also be used for their antioxidant
      properties. Therefore the antioxidant effects of the newly synthesized compounds
      were investigated in vitro by means of their inhibitory effect on hydrogen
      peroxide-induced erythrocyte membrane lipid peroxidation (EMLP) and on various
      erythrocyte antioxidant enzymes viz. superoxide dismutase (SOD), catalase (CAT)
      and glucose-6-phosphate dehydrogenase (G6PD). The synthesized benzimidazole
      derivatives showed remarkable antioxidant activity in vitro in the H2O2-induced
      EMLP system. Furthermore their effects on various antioxidant enzymes are
      discussed and evaluated from the perspective of structure- activity
      relationships.

PMID- 16789441
TI  - Ankle morphometry on 3D-CT images.
AB  - Understanding three-dimensional (3D) morphology of the ankle is essential for a
      better total ankle replacement. Current designs neither mimic the articular
      geometry at the bearing surface interfaces nor match the native bony bed with the
      implant's external dimensions. This is likely due to insufficient anthropometric
      data on sizing and geometry. We performed this study to determine the range of
      possible sizes of ankle joints based on high-resolution 3D-CT images. Clinical 3D
      CT images from twenty-one normal ankles (11 males, 10 females) were subjected to
      morphometric evaluation. A local coordinate system for measurement was
      established based on talar anatomic landmarks. Measurements included the width of
      the superior talar dome surface (measured at the anterior, middle, and posterior
      portions) and the arc radius of the talar dome. The results yielded an average
      anterior width of 29.9 +/- 2.6 mm, a middle width of 27.9 +/- 3.0 mm, and a
      posterior width of 25.2 +/- 3.7 mm. The talar dome radius was 20.7 +/- 2.6 mm.
      The width linearly decreased from anterior to posterior (p < 0.001). A
      significant gender difference was found in both the width and the radius (p
      values < 0.05), except at the middle width (p = 0.07). The data describe talar
      topography in a Caucasian U.S. adult cohort, suggesting the capability of the 3D
      CT approach for ankle morphometric evaluation and sizing for the fabrication of
      total ankle replacements.

PMID- 16789442
TI  - Loading and boundary condition influences in a poroelastic finite element model
      of cartilage stresses in a triaxial compression bioreactor.
AB  - BACKGROUND: We developed a poroelastic finite element (FE) model of cartilage in
      dynamic triaxial compression to parametrically analyze the effects of loading and
      boundary conditions on a baseline model. Conventional mechanical tests on
      articular cartilage such as confined and unconfined compression, indentation,
      etc., do not fully allow for modulation of compression and shear at physiological
      levels whereas triaxial compression does. A Triaxial Compression Bioreactor, or
      TRIAX, has been developed to study chondrocyte responses to multi-axial stress
      conditions under cyclic loading. In the triaxial setting, however, a cartilage
      explant's physical testing environment departs from the ideal homogeneous stress
      state that would occur from strict linear superposition of the applied axial and
      transverse pressure. METHOD OF APPROACH: An axisymmetric poroelastic FE model of
      a cartilage explant (4 mm diameter, 1.5 mm thick) in cyclic triaxial compression
      was created. Axial and transverse loads (2 MPa at 1 Hz.) were applied via a
      platen and containment sheath. Parameters of interest included the rise time and
      magnitude of the applied load, in addition to the containment sheath modulus and
      the friction coefficient at the cartilage/platen interfaces. Metrics of interest
      in addition to whole explant axial strain included axial (surface normal) stress,
      shear stress, pore pressure, and the fluid load carriage fraction within the
      explant. RESULTS: Strain results were compared to experimental data from explants
      tested in the TRIAX under conditions similar to the baseline model. Explant
      biomechanics varied considerably over numbers of load cycles and parameter
      values. Cyclic loading caused an increase in accumulated strain for the various
      loading and boundary conditions. CONCLUSIONS: Unlike what would be expected from
      linear superposition of the homogeneous stresses from the applied axial and
      transverse pressure, we have shown that the stress state within the TRIAX is
      considerably heterogeneous. Both the boundary influences (variation in the sheath
      modulus and friction coefficient) and the loading history (due to poroelastic
      material behavior) interact in a highly nonlinear manner to influence that
      heterogeneity.

PMID- 16789443
TI  - Assessing angiogenesis during fracture healing.
AB  - Angiogenesis, the sprouting of new capillaries from existing blood vessels, is
      crucial for normal fracture healing. Angiogenesis is a complex process involving
      a variety of growth factors and several cell types. The mechanism regulating
      angiogenesis during fracture repair is not well understood, and the relationships
      between angiogenesis, chondrogenesis, and osteogenesis are also undefined. In
      vivo animal models have been useful for determining angiogenic mechanisms. In
      particular, a murine model has been developed that offers the advantages of easy
      animal handling, low cost, reliable healing, and the availability of molecular
      and genetic techniques for research. However, the small size of mice provides
      challenges, including the inability to assess vascularization using techniques
      that have been employed in larger animals. Therefore, we developed and optimized
      techniques specifically for studying angiogenesis during mouse fracture repair.
      These techniques include blood vessel casting, micro-computed tomography (micro
      CT), immunohistochemistry, in situ hybridization, and genetic labeling of
      endothelial cells. Blood vessel casting and micro-CT are useful for visualization
      of small blood vessels. Immunohistochemistry using anti-PECAM (platelet
      endothelial cell adhesion molecule) or CD34 antibodies and genetic approaches
      using Tie2-cre transgenic mice can be used to label endothelial cells, visualize
      blood vessels including capillaries, and provide structural information about the
      vascularization of the fracture callous. Lastly, expression patterns of important
      growth factors regulating angiogenesis could be assessed by molecular approaches
      such as in situ hybridization.

PMID- 16789444
TI  - Medium-term follow-up of Achilles tendon lengthening in the treatment of ankle
      equinus in cerebral palsy.
AB  - INTRODUCTION: The optimal treatment for equinus of the ankle in ambulatory
      patients with cerebral palsy is not known. This study assessed the medium term
      follow-up results of treatment of spastic ankle equinus deformity in cerebral
      palsy using Hoke or coronal Z-lengthening of the Achilles tendon. It was
      hypothesized that the use of Achilles tendon lengthening (TAL) as a treatment for
      spastic ankle equinus during gait results in a high rate of over-weakening of the
      triceps surae resulting in crouch gait. We also investigated patient
      characteristics that could identify which patients are at risk for crouch gait
      due to triceps surae weakening from Achilles tendon lengthening. MATERIALS AND
      METHODS: Seventy-nine patients (114 procedures) who had undergone Achilles
      lengthening were retrospectively reviewed to determine how many patients
      developed crouch gait with dorsiflexion of the ankle throughout stance phase
      requiring anterior-floor-reaction bracing. The following patient characteristics
      were evaluated: age at surgery, geographic type of cerebral palsy, length of
      follow-up, need for anterior-floor-reaction bracing, length of time after surgery
      when brace was prescribed, age at time of need for bracing, side of surgery,
      technique used, additional procedures performed at time of TAL, previous or later
      procedures performed, and walking ability. RESULTS: The average age at the time
      of TAL was 7 years and 3 months, and the average follow-up was seven years. The
      geographic type of cerebral palsy greatly affected the outcome. None of the
      twenty-three hemiplegic patients required bracing. Fourteen of 34 (41%) patients
      with spastic diplegia and seven of fourteen (50%) patients with spastic
      quadriplegia required bracing. There was no significant difference in outcome
      between the Hoke and the Z-lengthening procedures. Patients who underwent more
      procedures and bilateral procedures were more likely to require anterior-floor
      reaction bracing. CONCLUSIONS: Achilles tendon lengthening as practiced by the
      senior author results in a high rate of over weakening of the triceps surae as
      defined by the need for a floor reaction brace. Results are best in patients with
      hemiplegia and non-hemiplegic patients who require only single leg surgery, and
      who do not require concomitant or subsequent surgery. Alternative treatment, such
      as gastrocnemius fascial lengthening, or non-surgical treatment may be the
      optimal treatment of ambulatory patients with spastic diplegia and quadriplegia
      who have spastic ankle equinus during gait.

PMID- 16789445
TI  - Comparison of fracture versus radiolucent table in the treatment of slipped
      capital femoral epiphysis.
AB  - PURPOSE: Compare slipped capital femoral epiphysis stabilized on fracture versus
      radiolucent table. METHODS: Twenty unilateral stable mild slipped capital femoral
      epiphyses were stabilized in-situ with a single screw. Age, sex, side, body-mass
      index, type of table, anesthesia time, surgery time, fluoroscopy time, number of
      fluoroscopy images, preoperative/postoperative lateral head-shaft angle, and
      number of screw threads engaging the epiphysis were noted. RESULTS: There were no
      differences in the measured parameters. CONCLUSIONS: Stabilization of mild
      slipped capital femoral epiphysis can be accomplished reliably and safely with
      the use of either a radiolucent or fracture table.

PMID- 16789446
TI  - Bone plating in patients with type III osteogenesis imperfecta: results and
      complications.
AB  - The results of bone plating in four children (6 femurs, 2 tibias) with
      osteogenesis imperfecta type III were analyzed. Average age at time of operation
      was 44 months. In three of the femurs, multiple platings were performed for a
      total of 13 bone platings in the eight bones studied. Average time to revision
      following plating was 27 months. Indications for revision included fracture (6),
      deformity (3), hardware failure (3), and nonunion (1). Other complications
      included one case of compartment syndrome. All eight bones were ultimately
      revised to elongating intramedullary Bailey-Dubow rods. Bone plating in
      skeletally immature patients with osteogenesis imperfecta does not provide better
      outcome than elongating rods. Complications from bone plating leading to
      revision, such as refracture or hardware failure, are higher than in those
      children managed with elongating rods, as previously reported in the literature.

PMID- 16789447
TI  - Sagittal knee kinematics following hamstring lengthening.
AB  - The purpose of this study was to analyze sagittal knee kinematics following
      hamstring lengthening. A retrospective analysis was performed of 16 children (32
      knees) with cerebral palsy who underwent hamstring lengthening as an isolated
      surgical procedure. Gait analysis was performed prior to surgery and at a minimum
      of one year after surgery. Decreased stance maximum knee flexion, stance minimum
      knee flexion, swing maximum knee flexion, and swing minimum knee flexion were
      noted. Total knee excursion increased. The present study confirmed the previously
      reported increase in total knee excursion with decrease in stance minimum and
      swing maximum knee flexion after hamstring lengthening.

PMID- 16789448
TI  - Septic arthritis in a Nigerian tertiary hospital.
AB  - BACKGROUND: Septic arthritis is a disabling disease that requires early diagnosis
      and prompt management for optimal outcome. Late presentations with deformities
      were noticed in our clinic. The aim of this study was to determine the pattern of
      septic arthritis in our environment. METHODS: This was an 18-month prospective
      study in a Nigerian teaching hospital. Thirty-nine consecutive patients with 45
      incidences of septic arthritis were studied. Joint aspirates were taken for
      microbiologic investigation. RESULTS: Patient ages ranged between 0.5-60 years
      and the mean age was 7.4 years. The male to female ratio was 2.9:1, and the knee
      was the most commonly affected joint. The duration of symptoms before
      presentation ranged between 4-17 days with a mean of 11.1 +/- 3.6 days. Twenty
      five (64.1%) of the patients were on inadequate antibiotics before presentation.
      Seventy-three percent of septic arthritis involving the upper limb joints
      occurred below the age of one year and 92.3% of the involved lower limb joints
      occurred after one year of age. CONCLUSION: The upper limb joints were
      significantly affected below one year of age and the joints of the lower limb
      were more involved after one year of age (p = 0.001). Improper prescription of
      antibiotics before presentation to the hospital was noticed in 64.1% and should
      be discouraged.

PMID- 16789449
TI  - The effects of silver coated external fixation pins.
AB  - We performed a randomized controlled trial in order to assess the effect silver
      coating of an external fixator pin has on pin infection. The experimental silver
      coated pins (SC) were compared to control stainless steel (SS) pins. A clamp
      design monolateral fixator was used, and pins were randomized to clamp position
      to allow side-by-side comparisons of pins in a similar environment. Nineteen
      patients and 33 clamps were entered and completed the study. There were no
      significant differences between the two types of pins in the rate of pin tract
      infection, clinical appearances of the pin sites, bacteriology of the pin tracts,
      torque to remove the pins, or radiographic lucency around the pin. We concluded
      that with the numbers available in this study, there were no detectable
      differences between the performance of SC and SS pins.

PMID- 16789450
TI  - Amputation osteoplasty.
AB  - Amputation osteoplasty is a technique modification promoted by Ertl to enhance
      rehabilitation after transtibial amputation. Two different techniques for
      creating sealing of the medullary canal and a distal bone block have been
      described in the literature. One technique consists of a periosteal sleeve that
      is sutured over the cut end of the bone. The second technique consists of hinging
      a segment of fibula into a slot in the cut end of the tibia. The desired goal of
      amputation osteoplasty is to create an end-bearing limb to enhance
      rehabilitation. In addition to creation of a bone bridge, Ertl also recommends
      myoplasty, neuroplasty, individual vessel ligation, and a special skin closure.
      This report is a small case series of five patients successfully treated with
      lower extremity amputation osteoplasty, to illustrate the techniques and report
      initial good results. Two patients had each of the techniques and one patient had
      both of the techniques. All five patients had good wound healing, accelerated
      rehabilitation, and the ability to use end-bearing prostheses.

PMID- 16789451
TI  - Intrapelvic migration of the trial femoral head during total hip arthroplasty: is
      retrieval necessary? A report of four cases.
AB  - When testing intra-operative range of motion during a total hip arthroplasty
      procedure with trial components, there is potential for the femoral head to
      dissociate from the trial neck. We report the dissociation of the trial femoral
      head with migration of the head into the pelvis while checking for anterior
      stability of the total hip arthroplasty construct. Options for retrieval of the
      head are outlined.

PMID- 16789452
TI  - Surgical procedure profile in a comprehensive hip surgery program.
AB  - Surgical management of hip disease in adolescents and young to middle-aged adults
      is rapidly evolving, and a variety of operative techniques are needed to provide
      comprehensive care. The purpose of this study was to determine the utilization of
      surgical procedures and recent changes in procedure utilization in a
      comprehensive hip surgery program. We performed a retrospective review of 983 hip
      procedures in 854 patients performed over a seven year time period. The average
      patient age was 37.4 years (range 10-55). Five hundred fifty-six procedures were
      performed in female patients and 427 in male patients. Total hip arthroplasty
      (32.9%), hip arthroscopy (25.1%), and periacetabular osteotomy (13.1%) were the
      most common surgical procedures. Techniques utilized less often included
      osteochondroplasty of the femoral head-neck junction (7.9%), hip implant
      revisions (7.9%), and proximal femoral osteotomy (4.1%). Uncommon procedures
      included core decompression (2.2%), soft tissue releases (1.2%), femoral head
      resurfacing (0.6%), arthrodesis (0.3%), and Chiari pelvic osteotomy (0.2%). The
      most dramatic changes in utilization over the seven year time period included a
      marked increase in hip arthroscopies and osteochondroplasties of the femoral head
      neck junction. These data underscore the variety of surgical techniques needed to
      treat this patient population, and emphasize an expanding role for
      nonarthroplasty surgical interventions.

PMID- 16789453
TI  - Ethanol as a local adjuvant for giant cell tumor of bone.
AB  - Giant cell tumor is an aggressive benign neoplasm of bone. A number of adjuvant
      agents have been used to supplement intralesional curettage to reduce the
      otherwise high local recurrence rate. High concentration ethanol is more readily
      available and less toxic to use than some common alternatives. No report on its
      use in a group of patients with giant cell tumor is available. Records were
      retrospectively reviewed for all giant cell tumors treated by intralesional
      curettage and high concentration ethanol irrigation as the only chemical
      adjuvant. Twenty-five primary excisional curettages and 12 repeat curettages for
      giant cell tumors of bone were performed in 31 patients. Patients were followed
      for a mean of three years and 10 months. There were five recurrences after
      primary excision procedures, and three after repeat excisions. Only use of a high
      speed burr and lower Campanacci staging correlated with reduced recurrence rate,
      and these were not statistically significant. Most defects were filled with
      allograft or calcium sulfate. In the 11 patients treated primarily with curettage
      using a high-speed burr and adjuvant ethanol with minimum two-year follow-up,
      only one stage 3 lesion in a distal radius recurred. Multiple washes with high
      concentration ethanol, when used in conjunction with aggressive curettage
      including high-speed burring, is an effective and safe adjuvant. The necessity of
      any chemical adjuvant after appropriately aggressive curettage and burring can
      only be definitively demonstrated with a prospective, randomized, multi-center
      trial. Until such evidence becomes available, the use of adjuvant ethanol offers
      a compromise between higher toxicity adjuvants and no chemical adjuvant at all.

PMID- 16789454
TI  - MCL injuries of the knee: current concepts review.
AB  - Medial collateral ligament (MCL) injury is one of the most common knee injuries,
      especially in young athletic patients. Most MCL injuries can be managed
      conservatively with good results. However, a complete understanding of knee
      anatomy and the involved structures is necessary to make intelligent treatment
      decisions. We will review the anatomy and biomechanics of the MCL, classification
      systems for MCL injuries, and operative and nonoperative treatment for acute and
      chronic MCL injuries.

PMID- 16789456
TI  - The state of physical medicine and rehabilitation in Iowa: 2000-2005.
AB  - BACKGROUND: The purpose of this study was to to describe the practice of physical
      medicine and rehabilitation within Iowa from 2000-2005 by conducting a survey of
      the 30 practicing physical medicine and rehabilitation physicians in Iowa.
      RESULTS: Nine of 15 respondents completed medical school or residency training in
      midwest states. Physiatrists expressed numerous concerns including poor
      reimbursement, increasing malpractice costs, and difficulty recruiting
      physiatrists to Iowa. Iowa is ranked 49th in physical medicine and rehabilitation
      physicians per capita population. It also ranks 50th in Medicare payments per
      enrollee, yet is ranked fourth in the nation for percentage of citizens over the
      age of 65. CONCLUSIONS: Recruitment of physical medicine and rehabilitation
      physicians should be tailored toward resident physicians completing training
      programs from midwest states. Retention of Iowa physiatrists, due to Iowa's lack
      of a physical medicine and rehabilitation residency training program, low
      Medicare reimbursement, and high percentage of patients over the age of 65, may
      lead to a "perfect storm" public health crisis for Iowans regarding the
      availability of future physical medicine and rehabilitation services.

PMID- 16789455
TI  - Patient location strategies for pediatric long-term follow-up studies.
AB  - BACKGROUND: Poor follow-up rates greatly diminish the validity of prospective and
      long-term studies. Therefore, locating patients is of critical importance. This
      is especially true in populations treated during childhood because addresses will
      change several times in intervening years. Recent publications have reported new
      strategies for patient location. The purpose of this study is to test an
      algorithm proposed by King et al., as well as other search methods, using a
      cohort of patients treated for clubfoot in childhood METHODS: The study
      population included 126 patients with clubfeet treated between 1950 and 1967. We
      followed the search algorithm proposed by King et al. In addition, we used state
      driver's license records, Reunitetonight.com, and Intelius.com. Patients were
      considered to be found when they returned a postage-paid reply letter or were
      contacted by phone. RESULTS: Using web pages recommended by King et al. we
      located 26 of 126 (21 percent) patients. Operator directory assistance failed to
      locate any patients not located by free internet sources. Additional websites had
      varied results. State driver's license records found 25 patients.
      Reunitetonight.com found none with thirty attempted. The best search engine was
      Intelius.com which located 68 out of 126 (54 percent) patients. CONCLUSION: The
      algorithm proposed by King et al. is not effective for long-term follow-up
      studies of pediatric populations. Intelius.com is worth the small fee charged
      (dollar 22.45) as it was the most effective method of locating patients.

PMID- 16789457
TI  - Outpatient pain rehabilitation programs.
AB  - Outpatient pain rehabilitation programs that include an interdisciplinary
      approach have been shown to be effective treatments for patients with chronic
      pain. The objectives of this article are to describe the common interdisciplinary
      pain rehabilitation programs available, the appropriate indications for use, the
      components of typical pain rehabilitation programs, the short-term and long-term
      success rates, the costs of attending these programs, and the significant
      societal costs of those patients who do not complete these programs and do not
      return to work.

PMID- 16789458
TI  - Randomized surgical trials and "sham" surgery: relevance to modern orthopaedics
      and minimally invasive surgery.
AB  - Surgical techniques are constantly changing and evolving, though research trials
      supporting the value of a specific surgical intervention are often limited by the
      lack of a legitimate control group. In surgical trials, the use of a placebo, or
      a "sham" surgery, is controversial. This article explores the debate regarding
      the use of sham surgeries and summarizes the few surgical studies that have used
      them. Arguments for and against their use in research are presented.

PMID- 16789459
TI  - Concomitant ipsilateral femoral neck and femoral shaft fracture nonunions: a
      report of three cases and a review of the literature.
AB  - Ipsilateral femoral neck and femoral shaft fractures are rarely reported in the
      literature and represent a diagnostic and treatment challenge. Due to the
      possibility of missing a nonunion at either site, we recommend a high clinical
      suspicion and careful radiographic examination of both fracture sites. Because
      the development of nonunion at both sites is exceedingly rare, we report three
      cases of concomitant ipsilateral femoral neck and shaft nonunions that were
      treated by the senior author (KAE). Two patients were treated with a Pauwels
      osteotomy and a blade plate for the femoral neck nonunion and a reamed retrograde
      intramedullary nail for the shaft. One patient was treated with an antegrade
      reamed cephalomedullary intramedullary nail. All three patients' fractures united
      at a mean of 4.6 months and they are currently pain free and without physical
      limitations.

PMID- 16789460
TI  - Neurogenic atrophy of the medial head of the gastrocnemius presenting in a toe
      walker: a case report.

PMID- 16789461
TI  - Dislocation of the posterior tibial tendon: a literature review and presentation
      of two cases.
AB  - Dislocation of the posterior tibial tendon has rarely been reported in the
      English literature. The most common mechanism is a traumatic injury. We present
      two patients with a traumatic dislocation. One patient was delayed in
      presentation to the treating physician by seven months. The second patient
      presented within one week. Both underwent surgical stabilization with repair of
      the torn retinaculum and deepening of the groove posterior to the medial
      malleolus. They have both returned to their pre-injury level of activity without
      any recurrence of dislocation.

PMID- 16789462
TI  - Proximal tibiofibular synostosis as a source of ankle pain: a case report.
AB  - We report the case of a 61-year-old man who presented with ankle pain of unknown
      etiology. The actual cause for his pain was missed during his two initial visits
      when only ankle radiographs were taken. During his third visit, a full-length
      tibia film revealed a proximal tibiofibular synostosis. He successfully underwent
      a fibular osteotomy with complete symptomatic relief. A literature review of this
      topic is presented.

PMID- 16789463
TI  - Correction of genu recurvatum secondary to Osgood-Schlatter disease: a case
      report.
AB  - Complications secondary to Osgood-Schlatter disease are rare, and there have been
      few reports on their treatment. Partial growth arrest of the proximal tibial
      physis as a result of Osgood-Schlatter disease has been infrequently described.
      Genu recurvatum from partial physeal arrest can cause cosmetic deformity,
      instability, pain, and weakness. We report a case of genu recurvatum secondary to
      Osgood-Schlatter disease treated successfully with proximal tibial osteotomy and
      distraction with a Taylor spatial frame.

PMID- 16789464
TI  - Parosteal osteosarcoma of the thumb metacarpal: a case report.
AB  - A 60-year-old man presented with increasing swelling of his right thumb, duration
      one year. Imaging studies demonstrated a bone-forming lesion extending from the
      dorsal cortex of the thumb metacarpal and involving the underlying medullary
      canal. Incisional biopsy yielded the diagnosis of parosteal osteosarcoma. The
      differential diagnosis for and rarity of parosteal osteosarcoma arising in the
      tubular bones of the hand are discussed.

PMID- 16789466
TI  - Secondary aneurysmal bone cyst of the patella: a case report.
AB  - A 20-year-old man presented to our clinic with pain and swelling in the right
      knee of one year's duration. Biopsy of the patella revealed an aneurysmal bone
      cyst secondary to a giant cell tumor. He was treated by curettage and bone cement
      to fill the defect. The rarity of this lesion in the patella and its treatment
      modalities are discussed.

PMID- 16789465
TI  - Intraosseous neurilemmoma involving the distal tibia and fibula: a case report.
AB  - Schwannoma, or neurilemmoma, is a benign nerve sheath tumor most commonly located
      in the soft tissue. Occasionally, Schwannomas involve osseous structures.
      Involvement of two adjacent long bones was not found in a review of the English
      language medical literature. We present the case of a neurilemmoma affecting both
      the distal fibula and tibia. Although rare, intraosseous neurilemmoma should be
      included on the differential diagnosis of painful, radiographically benign
      appearing lesions arising in long bones.

PMID- 16789467
TI  - Spontaneous septic arthritis caused by Burkholderia cepacia.
AB  - We describe the first reported case of a spontaneous septic arthritis caused by
      Burkholderia cepacia, the organism responsible for onion skin rot. The source of
      infection was most likely from hematogenous spread, as the patient's blood
      cultures were positive for B. cepacia. Treatment involved arthroscopic irrigation
      and drainage of the affected shoulder. Despite post-operative resolution of this
      immunocompromised patient's shoulder symptoms, he was unable to survive the B.
      cepacia bacteremia. Our report not only describes the case but also reviews the
      difficulty in treating B. cepacia infections.

PMID- 16789468
TI  - Multifocal skeletal tuberculosis: a report of three cases.
AB  - Tuberculosis of the bone is a well-recognized clinical condition that can be
      diagnosed and managed by physicians and orthopaedic surgeons, often with an
      excellent outcome. However, the occurrence of multifocal skeletal involvement in
      immunocompetent patients is rare, even in countries where tuberculosis is
      endemic. Patients with multifocal skeletal tuberculosis may present with multiple
      vague somatic symptoms. We report three cases of multifocal skeletal tuberculosis
      in non-immunocompromised patients. All three patients were effectively treated
      with antituberculous drugs.

PMID- 16789470
TI  - What constitutes good science in environmental and occupational health?

PMID- 16789469
TI  - The toxins of William B. Coley and the treatment of bone and soft-tissue
      sarcomas.
AB  - In 1891, William B. Coley injected streptococcal organisms into a patient with
      inoperable cancer. He thought that the infection he produced would have the side
      effect of shrinking the malignant tumor. He was successful, and this was one of
      the first examples of immunotherapy. Over the next forty years, as head of the
      Bone Tumor Service at Memorial Hospital in New York, Coley injected more than
      1000 cancer patients with bacteria or bacterial products. These products became
      known as Coley's Toxins. He and other doctors who used them reported excellent
      results, especially in bone and soft-tissue sarcomas. Despite his reported good
      results, Coley's Toxins came under a great deal of criticism because many doctors
      did not believe his results. This criticism, along with the development of
      radiation therapy and chemotherapy, caused Coley's Toxins to gradually disappear
      from use. However, the modern science of immunology has shown that Coley's
      principles were correct and that some cancers are sensitive to an enhanced immune
      system. Because research is very active in this field, William B. Coley, a bone
      sarcoma surgeon, deserves the title "Father of Immunotherapy".

PMID- 16789471
TI  - Health hazards from volcanic gases: a systematic literature review.
AB  - Millions of people are potentially exposed to volcanic gases worldwide, and
      exposures may differ from those in anthropogenic air pollution. A systematic
      literature review found few primary studies relating to health hazards of
      volcanic gases. SO2 and acid aerosols from eruptions and degassing events were
      associated with respiratory morbidity and mortality but not childhood asthma
      prevalence or lung function decrements. Accumulations of H2S and CO2 from
      volcanic and geothermal sources have caused fatalities from asphyxiation. Chronic
      exposure to H2S in geothermal areas was associated with increases in nervous
      system and respiratory diseases. Some impacts were on a large scale, affecting
      several countries (e.g., Laki fissure eruption in Iceland in 1783-4). No studies
      on health effects of volcanic releases of halogen gases or metal vapors were
      located. More high quality collaborative studies involving volcanologists and
      epidemiologists are recommended.

PMID- 16789472
TI  - Polycyclic aromatic hydrocarbon-DNA adducts and breast cancer: a pooled analysis.
AB  - Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with
      breast cancer in several small studies. The authors' pooled analysis included 873
      cases and 941 controls from a population-based case-control study. Competitive
      enzyme-linked immunosorbent assay in peripheral mononuclear cells was conducted
      in 2 rounds, and results were pooled on the basis of round-specific quantiles.
      The odds ratio for breast cancer was elevated in relation to detectable PAH-DNA
      adducts (1.29 as compared with nondetectable adduct levels; 95% confidence
      interval = 1.05, 1.58), but there was no apparent dose-response relationship with
      increasing quantiles. No consistent pattern emerged when the results were
      stratified by PAH sources (e.g., active cigarette smoking or PAH-containing
      foods), or when the cases were categorized by stage of disease or hormone
      receptor status. These data provide only modest support for an association
      between PAH-DNA adducts and breast cancer development.

PMID- 16789473
TI  - Gliomas and farm pesticide exposure in men: the upper midwest health study.
AB  - The National Institute for Occupational Safety and Health evaluated farm
      pesticide exposure and glioma risk in a study that included 457 glioma cases and
      648 population-based controls, all adult men (18-80 yr old) and nonmetropolitan
      residents of Iowa, Michigan, Minnesota, and Wisconsin. Multiple logistic
      regressions were used to control for farm residence, age, age group, education,
      and exposure to other pesticides. No associations were found between glioma and
      12 specific pesticides. We estimated adjusted odds ratios (ORs) and 95%
      confidence intervals (CIs) and found reduced glioma risk for insecticides (OR =
      0.53, CI = 0.37-0.77), fumigants (OR = 0.57, CI = 0.34-0.95), and organochlorines
      (OR = 0.66, CI = 0.47-0.94). In analyses excluding proxy respondents (47% of
      cases) most CIs included 1.0. No positive association of farm pesticide exposure
      and glioma was found. Other farm exposures may explain the excess brain cancer
      risk seen in previous studies.

PMID- 16789474
TI  - Determination of environmental exposure to asbestos (tremolite) and mesothelioma
      risks in the southeastern region of Turkey.
AB  - In this study, the authors examined the concentrations and mineralogical analyses
      of asbestos, and investigated mesothelioma risk in southeastern Anatolia, Turkey.
      They used a gravimetric dust sampler to collect samples from 2 villages and 2
      asbestos mines (1 active). Samples were then evaluated by an X-ray diffractometer
      and an electron microscope. The authors found high concentrations of asbestos in
      an active mine (4.9 fibers[f]/cm3) and at a house that was plastered with
      asbestos (1.24 f/cm3) and had a very active population. They found a low
      concentration (0.0042 f/cm3) in indoor measurements taken in Armutova village,
      and an even lower concentration (0.000081 f/cm3) in the inactive mine
      environment. Outdoor measurements included a low concentration of 0.007 f/cm3 in
      the village environment, and a high concentration of 1.17 f/cm3 on the mine road
      during the passing of a sheep herd. The people in the region are continuously
      exposed to asbestos during normal activities. This cumulative exposure to
      asbestos carries sufficient risks for mesothelioma development.

PMID- 16789475
TI  - Increased risks of term low-birth-weight infants in a petrochemical industrial
      city with high air pollution levels.
AB  - This study investigated the influence of petrochemical air pollution on birth
      weight. Birth data on 92,288 singleton infants with gestational periods of 37-44
      wk born in a petrochemical industrial city (Kaohsiung, n = 31,530) with severe
      pollution or a nonpetrochemical industrial city (Taipei, n = 60,758) in Taiwan
      between 1995 and 1997 were included in this analysis. Air pollutant concentration
      derived from routinely monitored data showed significantly higher concentrations
      of SO2, O3, and PM10 in Kaohsiung. Infants with low birth weight (LBW) were
      significantly more prevalent in Kaohsiung (2.4%) than in Taipei (2.1%).
      Multivariable logistic regression analysis with adjustment for gestation age,
      gender, birth order, season of birth, maternal age, and maternal education
      further suggested that LBW risk in Kaohsiung was 13% higher than that in Taipei
      (odds ratio [OR] = 1.13, 95%, confidence interval [CI] = 1.03-1.24).

PMID- 16789476
TI  - Air pollution, passive smoking, and respiratory symptoms in adults.
AB  - We studied the independent role of air pollution and passive smoking on
      respiratory symptoms and group of symptoms by following 46 adult nonsmokers for
      14 wk. Outcomes included the incidence of 15 symptoms. After adjustment for
      passive smoking, clear rhinorrhea and cough were positively related to nitrogen
      dioxide (NO2), particles (PM10), and black smoke (BS); whereas headache was
      positively related to BS. Sneezing, sore throat, and cough were independently
      positively related to passive smoking. After adjustment for passive smoking, the
      occurrence of groups of symptoms and of the "sore throat group" were related to
      three pollutants. The occurrence of the "possible infection group" was positively
      related to BS. The occurrence of every group of symptoms was independently
      related to passive smoking. In conclusion, the prevailing levels of air pollution
      and passive smoking had independent effects on symptoms and groups of symptoms.

PMID- 16789477
TI  - Effectiveness of clean indoor air ordinances in controlling environmental tobacco
      smoke in restaurants.
AB  - Clean indoor air (CIA) ordinances in Toledo, Ohio, and Bowling Green, Ohio,
      regulate smoking in restaurants to protect patrons and employees. Yet complete
      protection is questionable because the ordinances allow for smoking in certain
      dining sections. Two restaurants were studied in each city, one smoking and one
      nonsmoking. Levels of contaminants related to environmental tobacco smoke (ETS)-
      determined by personal and area air monitoring-in the nonsmoking restaurants were
      comparable to levels in a control environment. However, levels of ETS-related
      contaminants in the smoking restaurants, including designated nonsmoking
      sections, were significantly higher than levels in the control environment. ETS
      related contamination of the nonsmoking sections in the smoking restaurants is
      attributable to direct openings between the smoking and nonsmoking sections.
      Reasonable protection of employees and patrons against ETS-related contaminants
      requires strict enforcement of CIA ordinances. Full protection is achievable only
      with 100% smoke-free policies.

PMID- 16789478
TI  - Determination of urinary trace elements (arsenic, copper, cadmium, manganese,
      lead, zinc, selenium) in patients with Blackfoot disease.
AB  - To determine the relationship of arsenic, copper, cadmium, manganese, lead, zinc
      and selenium to Blackfoot disease (BFD, a peripheral vascular disorder endemic to
      areas of Taiwan, which has been linked to arsenic in drinking water) the authors
      measured the amount of these substances in urine from BFD patients, using atomic
      absorption spectrometry. Results indicate significantly higher amounts of urinary
      arsenic, copper, cadmium, manganese, and lead for BFD patients than for normal
      controls, also significantly lower urinary zinc and selenium.

PMID- 16789479
TI  - Evaluation of residential exposure to intermediate frequency magnetic fields.
AB  - The authors measured the exposure to intermediate-frequency (IF: 10 kHz to 30
      MHz) electromagnetic fields (EMF) in residential environments. They developed a
      system to acquire and record waveforms of IF magnetic fields (MFs) and set 5
      nanotesla (nT) for the trigger level of acquisition. They operated the system
      near power lines, railroads, and electrical appliances as possible sources of IF
      MFs. Most of the maximum values of magnetic flux density and the time derivative
      for each wave were below the upper limit of the measurable range of our system
      (i.e., 53 nT and 10 T/s); these values were much lower than the minimum
      amplitudes that can theoretically induce heating or membrane excitation within
      biological systems. Moreover, the amplitudes of the IF-MFs were not related to
      those of extremely low frequency (ELF) MF measured simultaneously, indicating
      that IF-MFs do not underlie the associations, observed in several epidemiological
      studies, between residential exposure to ELF-EMF and childhood cancer.

PMID- 16789480
TI  - Development and reduction of hypertension and oxidative stress among detergent
      industry workers.
AB  - Hypertension status and oxidative stress parameters were assessed in 291 workers
      (hypertensive workers were divided into three grades, non-equivalently) at two
      detergent production plants, one of which included enzymes in the detergent
      (n=138) and another which did not (n=153), and 45 control workers in another
      industry three times (at the time of employment, 7 yrs later at the time of
      installation of a filter system, and about 3 yrs later). Malondialdehyde (MDA)
      was measured by high-performance liquid chromatography, antioxidant enzymes and
      lipid status by ultraviolet-visible spectrophotometry, trace elements by atomic
      absorption spectroscopy, and blood pressure using an oscilometric device. Prior
      to filter system installation, enzyme-exposed workers had significantly higher
      MDA, antioxidant enzyme activities, and prevalence of hypertension, compared with
      controls. The filter system reduced airborne detergent and enzyme dusts,
      resulting in a decreased prevalence of hypertension and a significant improvement
      in workers' oxidative stress indicators. Alterations in antioxidant status may
      result from the cumulative effect of high levels of detergent and enzyme in
      airborne dust in the workplace.

PMID- 16789481
TI  - Association between exposure to cadmium and blood pressure in Japanese peoples.
AB  - The authors studied the effects of environmental cadmium exposure on blood
      pressure (BP). Subjects 1140 men and 1713 women, aged > or =50 yr lived in three
      areas of Japan considered "unpolluted" by cadmium. Multiple logistic regression
      analysis was used to evaluate relationships between hypertension/nonhypertension
      and cadmium concentrations in blood (B-Cd) or urine (U-Cd). Age, body mass index,
      drinking and smoking habits, and blood and urine chemistry data were incorporated
      into the model. Odds ratios for hypertension were significantly less than 1 in
      either gender when U-Cd was the indicator of cadmium exposure and hypertension
      was defined as systolic BP > or =140 mmHg and/or diastolic BP > or =90 mmHg. The
      results suggest a significant negative association between cadmium exposure and
      BP in inhabitants in Japan.

PMID- 16789482
TI  - Medical assessment of the health effects of short leisure trips.
AB  - Using responses to questionnaires and results of saliva samples from 40 women,
      the authors assessed the effects on health of participation in a short leisure
      trip (2 nights, 3 d) to Kyushu Island in Japan. They addressed transportation,
      sightseeing, and group activities during the tour, which might differ from
      participants' usual activities. Levels of the salivary endocrinological stress
      markers cortisol and chromogranin A (CgA) were determined by enzyme-linked
      immunosorbent assay (ELISA). In each of the groups with characteristics
      considered healthy and related to lifestyle, patterns of behavior, perceived
      stressors, and stress reactions, a decrease in the cortisol levels and an
      increase in the CgA levels were apparent during the tour. The baseline for stress
      hormone changes was the levels on awakening on Day 1 (i.e., immediately before
      the tour). These findings suggest that even short periods of travel can bring
      about a reduction in di-stress and acquisition of eu-stress, experienced as
      feeling uplifted or fulfilled.

PMID- 16789483
TI  - Relationship between health status and psychological distress among the
      inhabitants in a methylmercury-polluted area in Japan.
AB  - This study examined the relationship between health parameters and psychological
      distress among inhabitants of methylmercury-polluted areas in Japan. The subjects
      were 133 inhabitants over the age of 40 yr living in two methylmercury-polluted
      villages. Information on demographic factors, health status, and mental health
      was obtained using questionnaires, including the General Health Questionnaire
      (GHQ). The proportional odds model was used to estimate the adjusted odds ratios
      of factors associated with a higher GHQ score after adjustment for age, gender,
      and district. Very poor self-rated health status, a high number (5+) of
      subjective symptoms, having monthly outpatient visits and medical house calls,
      and receiving compensation for methylmercury poisoning were significantly
      associated with psychological distress. Poor physical condition may lead to the
      development of psychological distress.

PMID- 16789485
TI  - [Influence of hyaluronan on peritoneal permeability for macromolecules in vitro].
AB  - Recent studies pointed out advantages of high-molecular hyaluronic acid (HA)
      application into dialysis fluids. This molecule is an essential component of
      peritoneal extracellular matrix. The compound shows antiadhesive properties and
      participates in restoring of peritoneal integrality and remodeling of peritoneum,
      which have been changed by prolonged peritoneal dialysis and returning incidents
      of peritonitis. Influence of HA on transperitoneal transport of large and small
      molecules is recognized in a little range. The aim of presented studies in vitro
      was qualification of hyaluronan influence on transport dynamics of the selected
      macromolecules (albumin 1 g/dL, icodextrin 7.5 g/dL and insulin 0.1 g/dL). Values
      of the transfer, directed from the interstitial to the mesothelial side of
      membrane (I-->M) and in the opposite direction (M-->I) were expressed as
      coefficient of diffusive permeability P [cm/s]. In the case of each
      macromolecule, two separate research series of the experiments were done. In the
      first one transperitoneal transport in the control conditions (120 min) was
      analyzed, and in the secondtransfer parameters before (15-60 min) and after
      hyaluronan (0.04 g/dL) application on the mesothelial side of peritoneal membrane
      (75-120 min) were examined. Stability of albumin and insulin transport (in the
      case of the both transfer directions) and icodextin passage (only M-->I
      direction) was observed in the presented studies when we compare the first and
      the second hours of the experiments. In the opposite direction (I-->M) it was
      showed an increase of its transport with time by about 50%. The mean values of P
      +/- SEM amounted to 0,271 +/- 0,056 [x10(-4); cm/s] and 0,315 +/- 0,057 [x10(-4);
      cm/s] for albumin and 0,145 +/- 0,033 [x10(-4); cm/s] and 0,146 +/- 0,022 [x10(
      4); cm/s] for insulin, respectively in the case of I-->M and M-->I directions and
      0,194 +/- 0,035 [x10(-4); cm/s] for icodextrin transfer directed from the
      mesothelial to the interstitial side of membrane. In the opposite direction (I-
      >M) values of P coefficient amounted to: 0,280 +/- 0,038 [x10(-4); cm/s] in the
      first experimental hour, and 0,394 +/- 0,046 [x10(-4); cm/s] in the second one.
      It was observed also asymmetry of glucose polymer passage with I-->M transfer
      domination. Hyaluronan eliminated this asymmetry. After use this compound the
      transport parameters of icodextrin were stable for the both I-->M and M-->I
      directions. Hyaluronan did not change values of diffusive permeability
      coefficients P in the case of bidirectional transfer of albumin and insulin. The
      obtained results show, that values of macromolecules transfer across peritoneum
      in vitro don't depend on their molecular weight and isoelectric points. Dynamics
      of albumin and insulin transperitoneal passage is stable. Icodextrin transport,
      directed from the interstitial to the mesothelial side of membrane, predominates
      transfer in the opposite direction. Hyaluronan modifies dynamics of
      transperitoneal icodextrin passage, but doesn't influence on permeability of the
      membrane in the case of albumin and insulin.

PMID- 16789484
TI  - Exposure of a Cree population living near mine tailings in northern Quebec
      (Canada) to metals and metalloids.
AB  - The authors investigated the effect of residues from copper- and gold-mining on
      the Cree population of Ouje-Bougoumou, located 560 km north of Quebec City,
      Canada. Subjects (225) from Ouje-Bougoumou and a control population (100)
      completed a questionnaire on lifestyle and dietary habits and provided blood and
      urine samples for analysis. Geometric means of arsenic, lead, cadmium, and copper
      concentrations were not significantly different for subjects or controls 15 yr
      and older or children (8-14 yr old). However, blood zinc was higher and selenium
      was lower in Ouje-Bougoumou samples. Mean blood lead level was higher in children
      from Ouje-Bougoumou, but lower in adults aged 40 yr and older. For adults (15 yr
      and older) blood lead level increased with age and was higher in men, those who
      hunted, and consumed wild meat (R2 = 0.43). Blood cadmium increased with age and
      smoking (R2 = 0.61). No influence of mine residues was observed among residents
      of Ouje-Bougoumou, but lifestyle exposure associations were noted for both
      communities.

PMID- 16789486
TI  - [I/D polymorphism of angiotensin I converting enzyme gene and insulin resistance
      and some parameters of metabolic syndrome in patients with type 2 diabetes].
AB  - Insulinresistance is a component of the metabolic syndrome and important
      pathogenetic factor of type 2 diabetes mellitus. There are evidences that
      activation of the renin-angiotensin system (RAS) can decrease insulin sensitivity
      of tissues. As I/D polymorphism of angiotensin converting enzyme (ACE) gene can
      influence the activity of RAS, it may also influence insulin resistance. Aim. To
      assess the relationship between the I/D polymorphism of ACE gene and degree of
      insulin resistance and intensity of metabolic syndrome in type 2 diabetic
      patients. Study group and methods. Examined group: 108 type 2 diabetic patients
      (38 women and 70 men), with mean duration of disease 9.07 +/- 6.68 years, mean
      age 59.98 +/- 9.10 years. Assessed parameters: body mass index (BMI), waist/hip
      ratio (WHR), arterial blood pressure. Laboratory tests: concentration of the
      glycosylated hemoglobin (HbA 1c), glucose, insulin, total cholesterol, HDL and
      LDL cholesterol, triglycerides, creatinine, uric acid. Insulin resistance was
      calculated by the HOMA rate. Criterion of insulin resistance was rate > or = 2.5.
      The diagnosis and assessment of intensity of metabolic syndrome was performed
      according to criteria of National Education Cholesterol Adult Treatment Program
      the Panel III. I/D ACE gene polymorphism was evaluated by polymerase chain
      reaction (PCR). Results. Groups with 11, ID and DD genotype were not different in
      age, BMI, WHR, duration of diabetes, the prevalence and duration of arterial
      hypertension, degree of metabolic control and insulinresistance assessed by HOMA
      rate and intensity of metabolic syndrome. DD genotype carriers had significant
      higher systolic and diastolic blood pressure (147.8 +/- 19.8 mmHg vs 138.2 +/-
      16.5 mmHg, p = 0,02; 89.2 +/- 9.6 mmHg vs 81.7 +/- 8.6, p = 0,003, respectively)
      than II patients. Conclusion. In type 2 diabetic patients the I/D genotype of ACE
      gene is not associated with the increased insulin resistance assessed by HOMA
      rate and intensity of metabolic syndrome.

PMID- 16789487
TI  - [Clinical significance of exercise-induced ST-segment elevation in lead aVR and
      V1 in patients with chronic stable angina pectoris and strongly positive exercise
      test results].
AB  - Electrocardiographic abnormalities in lead aVR and V1 are rarely analyzed on
      exercise electrocardiograms. Clinical significance of exercise-induced ST-segment
      changes in lead aVR and V1 during strongly positive electrocardiographic exercise
      test (EET) in patients with chronic stable angina pectoris remains unclear. The
      aim of the study was to assess the value of lead aVR and V1 on the exercise
      electrocardiogram for the detection of left main coronary artery stenosis (LMCAS)
      and its equivalent (LMCASE) in patients with chronic stable angina pectoris and
      the strongly positive EET result. The study group consisted of 118 consecutive
      patients (mean age 58.8 +/- 9.5 years, range 38-77 years), including 30 (25.4%)
      women. Patients were divided into three groups. In group I, 31 patients with ST
      elevation in lead aVR and V1, in group II 66 patients with isolated ST elevation
      in lead aVR, and in group III 21 patients without ST elevation in lead aVR,
      induced with exercise, were included. Coronary arteriography results were
      compared among these groups. In patients with isolated exercise-induced ST
      elevation in lead aVR, the prevalence of LMCAS was five times more frequent than
      in patients without lead aVR ST elevation (25.8% vs 4.8% p<0.05). There were no
      differences in the prevalence of LMCASE and multi-vessel coronary disease in the
      studied groups. In patients with LMCAS significant ST elevation in lead aVR
      during strongly positive EET were observed (0.25 +/- 0,4 mm vs 1.43 +/- 0.6 mm p
      = 0.003), whereas there were no significant exercise-induced electrocardiographic
      changes in lead V1 (0.61 +/- 0.6 mm vs 0.77 +/- 0.6 mm p = 0.08). Sensitivity of
      isolated exercise-induced ST elevation in lead aVR in detection of LMCAS was
      85.0%, specificity - 50.0%, positive predictive value - 25.8%, negative
      predictive value - 94.2%, and total accuracy - 55.9%. Exercise-induced ST
      elevation in lead aVR on the strongly positive exercise ECG may detect LMCAS in
      patients with chronic stable angina pectoris.

PMID- 16789488
TI  - [Hepatitis B virus genotypes and the response to lamivudine therapy].
AB  - Hepatitis B virus (HBV) can be classified into eight major genotypes (A-H) that
      have mainly a geographic distribution. The HBV genotype may influence disease
      progression, HBeAg seroconversion rates, response to antiviral treatment. The aim
      of study was to analyze the distribution and frequency of genotypes in patients
      with chronic hepatitis B. Response to lamivudine 100 mg daily therapy was
      examined in respect to genotype. Sixty six patients (45 (68,2%) male, 21 (31,8%)
      female) with chronic hepatits B were enrolled. HBV genotypes were assigned before
      treatment with INNO-LiPA HBV Genotyping, Innogenetics, N. V., Ghent assay, which
      is a line probe test based on the reverse hybridization principle. In baseline
      and after 12 months of treatment serological markers of HBV infection, alanine
      aminotransferase (ALT) activities and HBV DNA serum levels were tested. Patients
      with chronic hepatitis B were infected predominantly with genotype A. HBV
      genotype distribution was: 78,8% for genotype A, 13,6% for genotype D, 1,5% for
      mixed infection with genotypes A and D. Distribution of genotypes A and D was
      asymmetrically regardless of sex, HBeAg status, ALT and HBV DNA levels. Four
      (6,1%) specimens had indeterminate A results by LiPA. There were no significant
      differences between patients with genotypes A and D regarding age and sex. There
      were also no significant differences between these two groups regarding rates of
      HBeAg and anti-HBe positivity, ALT activity and viral load. Twenty months of
      lamivudine (100 mg daily) therapy resulted in significant decreases in serum HBV
      DNA and ALT activities in patients with genotype A as well as with genotype D.
      After 12 months of treatment there were no statistical differences in HBeAg
      seroconversion rates, ALT activities, viral loads, frequency of HBeAg and anti
      HBe between genotypes A and D.

PMID- 16789489
TI  - [Negative D-dimers and exclusion of venous thromboembolism--own experience].
AB  - The assessment of D-dimer concentration has become essential step during
      diagnostic algorithm of venous thromboembolism (VTE). This test characterizes
      high sensitivity but limited specificity. Negative D-dimer with high probability
      excludes VTE. The aim of this study was to assess the percentage of patients
      treated in Department of Internal Medicine, Endocrinology and Haemostatic
      Disorders, Medical University of Gdanisk, who in spite of clinical signs of VTE
      showed normal D-dimer level. Between 2000 and 2004 in our department 57 cases
      with recent deep vein thrombosis (DVT) were diagnosed, in 2 cases with co
      existence of pulmonary embolism (PE). The D-dimer concentration was assessed in
      patients' plasma with the use of immunoturbidometry. Between 57 cases with VTE, 7
      patients (12%) showed normal D-dimer level (<500 microg/ml). This group consisted
      of 4 men and 3 women, aged from 40 to 82 years (the mean age of 58 years). In all
      7 cases DVT was diagnosed, in 2 patients with concomitent PE. The final diagnosis
      was confirmed by compression ultrasonography and pulmonary scintigraphy. Our
      analysis underlines the observation that occurrence of VTE and negative d-dimer
      concentration is possible and may probably be related to methodological
      limitations. However, the lack of increase of D-dimer could also be caused by
      fibrinolysis alteration.

PMID- 16789490
TI  - [Feasibility of home self-administration of low molecular weight heparin by
      patients with atrial fibrillation recurrence. A new approach to thromboembolic
      prophyllaxis].
AB  - We checked the feasibility of self-screening for atrial fibrillation (AF) by
      instructed patients pts and prompt home self-administration of an initial dose of
      low-molecular weight heparin (LMWH) prior to seeking medical attention.
      INVESTIGATED GROUP AND METHODS: Pts with persistent AF and low risk of systemic
      embolisation qualified to elective cardioversion (CV) were the subjects of our
      interest. All pts were trained to identify AF by palpation of the radial pulse
      and to self-inject LMWH in case of arrhythmia recurrence. 232 pts (mean age 59.8
      +/- 8.6 years) who maintained sinus rhythm (SR) during 4 weeks following
      successful cardioversion (CV) and correctly recognized AF recurrence and those
      without episodes of AF were equipped with nadroparine after acenocoumarol
      discontinuation. Thromboembolic prophylaxis was continued with antiplatelets
      agents or those no additional risk factors of systemic embolisation were left
      without medical therapy. RESULTS: 191 pts had AF recurrence during the mean 2.6
      +/- 1.7 years observation period, 172 of them correctly identified AF episode,
      including 162 who performed LMWH injections at home. 7 pts, who had performed
      LMWH injections, presented with SR on arrival to hospital, 6 pts had AF1.2 out of
      21 pts who failed to identify their AF episodes and 1 pt of those who correctly
      detected the AF recurrence but failed to perform LMWH self-injection suffered
      from ischemic stroke (sensitivity 96.1%, specificity 60.4%). No side effects of
      domiciliary LMWH self-injection were found. CONCLUSION: When properly trained,
      the majority of pts can accurately diagnose AF recurrence and self-inject initial
      dose of LMWH, what is feasible and may represent an attractive anti
      thromboembolic strategy.

PMID- 16789491
TI  - [Hemolytic uremic syndrome].
AB  - Hemolityc anemia, thrombocytopenia and acute renal failure are characteristic
      features of hemolytic uremic syndrome (HUS). The disease occurs mainly in infants
      and little children, sometimes it occurs in adult people. Most often it occurs in
      the course of diarrhorea cause by E. coli O 157:H7. Many other agents can induce
      HUS. The case of 54 year old female with HUS which developed in the course of
      diarhoea was reported. The course of HUS was complicated by multiorgan--brain,
      heart, pancreas and liver injure. Hemodialysis and plasmapheresis were used in
      the treatment. The treatment made the health recovery possible in our case.

PMID- 16789492
TI  - [Gastric cancer in chronic lymphocytic leukaemia patient--case report].
AB  - B-cell chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia
      occurring in western countries and USA. Performed population study showed
      increasing risk of secondary neoplasms in this group of patients. A Richter's
      transformation (histologically aggressive lymphoid malignancy) is the most often
      subsequent kind of the cancers of CLL patients. Solid tumours such as cancer of
      lung, breast, skin, prostate belongs to other group of secondary neoplasm in CLL.
      There is no evidence of any correlation between secondary neoplasms incidence,
      CLL prognostic factors and stage of the disease. Our paper presents the case of
      CLL patient in early stage of the disease, having gastric cancer diagnosed.

PMID- 16789493
TI  - [Multiple brain tuberculomas].
AB  - A case of multiple brain tuberculosis in 32-year-old men was described. The
      diagnosis was made on the result of histopathological examination of excised
      tuberculoma. Basing on the described case, current possibilities of tuberculoma
      diagnostic difficulties, caused by unspecific clinical manifestation and atypical
      radiological lesions, was drawn.

PMID- 16789494
TI  - [Acute coronary syndrome in patients with chronic kidney disease--risk
      stratification].

PMID- 16789496
TI  - [Indications for calcium channel antagonist therapy according to the latest large
      clinical trials].

PMID- 16789495
TI  - [Prevention and treatment of osteoporosis].

PMID- 16789497
TI  - [Ischemia modified albumin--a new biochemical marker of myocardial ischemia].

PMID- 16789498
TI  - [Thyroid hormones disturbances in critical ill patients--low T3 syndrome].

PMID- 16789499
TI  - [Rules of management and treatment the patients with recurrent hepatitis C after
      liver transplantation].

PMID- 16789500
TI  - [Opening address of the president of the Polish Society of Internal Medicine
      presented at the 4th National Educational Conference "Internal Medicine 2005",
      Warsaw, June 167, 2005].

PMID- 16789501
TI  - [Osteopoikilosis and susceptibility to excessive cicatrix in tissues].

PMID- 16789502
TI  - [Which factors determine survival of patients on regular dialysis treatment?].

PMID- 16789504
TI  - [Impaired fasting glucose and silent myocardial ischemia].
AB  - The present study was designed to reveal the incidence of silent myocardial
      ischemia in asymptomatic elderly patients with impaired fasting glucose. Abnormal
      perfusion pattern was found in 13 of 48 (27.1%), who were finally considered to
      have a SMI. The evidence suggests that early and intensive detection may be
      needed as a part of routine care for this group.

PMID- 16789503
TI  - [Influence of polymorphism pro12Ala of PPARgamma gene on endothelium destruction
      in patients with diabetes mellitus t. 2].
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) influences wide
      on metabolism and atheromatosus processes in vessels. The common polymorphic form
      of PPARy, Pro12Ala, could promote diabetes mellitus and diabetic vascular
      complications. AIM OF WORK: The assessment of indicators of endothelium
      destruction in patients with diabetes mellitus t.2 in relation to the
      polymorphism Pro12Ala of PPARgamma. PATIENTS AND METHODS: Circulating blood
      endothelium cells (immunofluorescens method with MoAb CLB-HEC19), thrombomodulin
      (Asserchrom Immunoassay) and polymorphism Pro12Ala [minisequence technic SnaPshot
      (Applera); ABI+PRISM310] were investigated in 58 patients with diabetes mellitus
      typ 2 and 22 healthy persons. Fibrinogen, uric acid, lipids, HbA1c, glucose,
      insulin concentration, blood pressure, BMI and WHR were evaluated too. RESULTS:
      The significant higher systolic (137.92 +/- 15.88 vs 122.0 +/- 15,67 [mmHg]; p <
      0.025) and diastolic (85.00 +/- 7.38 vs 75.50 +/- 7.61 [mmHg]; p < 0.011) was
      determined in the group of healthy people, who have got a homozygous genotyp
      Pro12Pro in comparison with heterozygous genotyp Pro12Ala. The significant higher
      value of HbA1c was determined in the patients with diabetes mellitus t.2, who
      have got genotyp Pro12Ala in comparison with genotyp Pro12Pro (7.01 +/- 1.54 vs
      8.39 +/- 1.81 [%]; p < 0.006). There was any significant difference for others
      parameters. Among people, which have got genotyp Pro12Pro there was significant
      difference between healthy and patients for circulating blood endothelium cells
      (2.19 +/- 1.53 vs 0.78 +/- 0.09 [EC/ml]; p < 0.009). On the contrary among people
      with genotype Pro12Ala there was not significant difference between healthy and
      patients for circulating blood endothelium cells (2.95 +/- 1.64 vs 1.61 +/- 1.08;
      p = 0.077 [EC/ml]). CONCLUSIONS: 1) The polymorphism Pro12Ala is not connected
      with the endothelium destruction. 2) Other researches are necessary to estimate
      influence of mutated allele on the control of diabetes. 3) The genotyp Pro12Pro
      promotes higher blood pressure by healthy people.

PMID- 16789505
TI  - [Vascular stiffness in chronic renal failure patients treated by hemodialysis].
AB  - Cardiovascular disease is a major cause of morbidity in patients with end-stage
      renal failure. Arterial stiffness measured by pulse wave velocity (PWV) is an
      independent risk factor for morbidity in end stage renal failure patients. The
      aim of our study was to evaluate the arterial stiffness in patients with chronic
      renal failure. In 20 chronic renal failure patients treated by hemodialysis (HD)
      we assessed the PWV of the carotic artery as well as artery diameter and
      distensibility, systolic pressure (SBP), diastolic pressure (DBP), pulse pressure
      (PP), and basal biochemical parameters and compared them with the values
      determined in 20 healthy controls of comparable age. PWV and PP are significantly
      (p < 0.001, p < 0.05) higher and distensibility of the carotic artery was
      significantly lower (p < 0.001) compared to a control group SBP and DBP were <
      140/90 mmHg in HD patients (high normotensive range) but were significantly (p <
      0.05) higher than in a control group. In HD patients PP was correlated with
      arterial distensibility r = -0.600 (p < 0.005), and systolic artery rice r = 
      0.408 (p < 0.05). SBP was correlated with PP r = 0.689 (p < 0.0007) and with
      arterial distensibility r = -0.476 (p < 0.03), arterial diameter to systolic
      artery rice r = -0.463 (p < 0.03), systolic artery rice to arterial
      distensibility r = 0.885 (p < 0.00001), intima media to arterial distensibility r
      = 0.815 (p < 0.00001), intima media to arterial compliance r = 0.893 (p <
      0.00001). Our results suggest that not only established hypertension but also
      high normotensive pressure could cause arterial stiffness absened in chronic
      renal failure patients.

PMID- 16789506
TI  - [Asthma in the elderly--estimation of natural disease course].
AB  - Bronchial asthma in the elderly is the significant medical problem because it is
      often underdiagnosed and insufficiently treated. The aim of the study was the
      assessment of natural course of bronchial asthma and its diagnostic procedures
      and treatment in patients after 65 yrs. The study group consisted of 181 patients
      suffering from asthma, at mean age 69 +/- 2.1 yrs. Apart from retrospective
      analysis, spirometry, skin tests and serum IgE concentration were performed.
      RESULTS: The mean duration of asthma was 23 +/- 7.2 yrs and in most cases time of
      proper diagnosis was prolonged. 49% of elderly patients bad a positive history to
      atopy. In spirometry the mean value of FEV1 was 2.78 +/- 1.3 l/s. House dust
      mites were the most common allergen confirmed by skin prick tests and specific
      serum IgE level. CONCLUSION: The observations proved underdiagnosis and
      insufficient treatment of asthma in the elderly. Positive skin test and specific
      IgE observed in a large group of elderly objects can indicate atopic mechanism in
      these cases.

PMID- 16789507
TI  - [Mitral valve prolapse at pregnancy--is it a real clinical problem?].
AB  - Mitral valve prolapse (MVP) effects more often young women. Symptomatology of MVP
      varies, symptoms are often nagging and some complications are of importance
      (mitral insufficiency and arrhythmias). Main objective of investigation was:
      estimation of the frequency and symptomatology of MVP during pregnancy. A group
      of 120 women in II/III of pregnancy were admitted to the maternity ward, where
      echocardiography and a survey have been performed. Two criteria were considered
      as the classical MVP: displacement toward the left atrium at > 2 mm and the
      thickness of valve > or = 5 mm. In case when the first criterion was fulfilled,
      the diagnosis was MVP non classic, in the second case MVP named non classic 2.
      Classical MVP was diagnosed in 10 patients--8.3% of the examined group. The group
      of 22 patients--18.3% was diagnosed MVP named non classic 2. MVP during pregnancy
      is frequent, it accounts for 8.3%. Varies symptomatology was characteristic for
      all the groups MVP. The most frequent complaints were: dizziness, palpitation,
      and faintness. There were observed statistically more often in the group with
      MVP. Women with MVP are not protected by pregnancy.

PMID- 16789508
TI  - [Primary hypoparathyroidism and hypergonadotropic hypogonadism in a male patient
      with common variable immunodeficiency. A case report].
AB  - We describe here a case of a 42-year-old male patient with severe
      hipogammaglobulinemia primary hypoparathyroidism and hypogonadism, various G1
      disorders, malabsorption syndrome, anemia and recurrent severe sinopulmonary
      infections. We present also difficulties and limitations relating to diagnosis of
      common variable immunodeficiency and shortly present review of literature.

PMID- 16789509
TI  - [An unusual clinical presentation of the autoimmune polyendocrine syndrome].
AB  - Organ-specific autoimmune endocrine disorders may occur together in autoimmune
      polyendocrine syndromes (APS). The diverse names given to APS and the
      underestimation of their real frequency reflect the large number of studies and
      case reports concerning these patients and heterogeneity in their clinical
      presentation. In this article we report the case of a 64-year-old man, initially
      diagnosed with Addison's disease and type 2 diabetes mellitus. Clinical
      examination, laboratory tests and radiological examination revealed the presence
      of co-existing Graves' disease and enabled us to classify the type of his
      diabetes as latent autoimmune diabetes in adults (LADA). Taking into account all
      his disorders, we assume that our patient suffers from a variant of type 2 APS.
      In the described state of the examined patient, accurate diagnosis, modification
      of hitherto treatment and implementation of new treatment strategies not only
      improved his clinical status but also allowed avoiding unnecessary administration
      of some drugs. This case illustrates the need for clinical awareness of APS in
      patients with any diagnosed autoimmune endocrine disorder.

PMID- 16789511
TI  - [Current view on pathogenesis of gastric cancer].

PMID- 16789510
TI  - [Lupus erythematosus or human immunodeficiency virus infection? Diagnostic
      problems in rheumatologic practice--two case reports].
AB  - It may bring a lot of diagnostic difficulties to differenciate the systemic lupus
      erythematosus (SLE) and the infection with human immunodeficiency virus (HIV),
      since there are many multiorgan symptoms that are common for both of these
      diseases. Two case reports of patients with lupus-like syndrome, being the first
      manifestation of HIV infection, are described in this article. The aim of the
      article is to stress the importance of a very careful differentiating of SLE and
      HIV infection.

PMID- 16789512
TI  - [Glycemic index and obesity].

PMID- 16789513
TI  - [Tumour markers of pancreatic cancer--Part II (molecular markers of
      carcinogenesis and non-specific tumour markers)].

PMID- 16789514
TI  - [Myelodysplastic syndromes--from FAB to WHO classification].

PMID- 16789515
TI  - [Risk of atherosclerosis development in patients with systemic lupus
      erythematosus].

PMID- 16789517
TI  - [Opening address of the President of the Polish Society of Internal Medicine
      delivered at the 4th National Educational Conference "Internal Medicine 2005",
      Warsaw, June 17, 2005].

PMID- 16789516
TI  - [The influence of hyperthyroidism and glucocorticoids on bone metabolism].

PMID- 16789518
TI  - [Value of electrocardiographic treadmill test for rate control strategy in
      permanent atrial fibrillation].
AB  - AIM: of our study was to determine the correlation between physical activity
      tolerance assesed by exercise tolerance test (ETT) and dynamics of change of
      echocardiographic parameters of left atrium (LA) and left ventricle (LV) in
      standard transtoracic echocardiography (TTE) in long-term follow up of patients
      with persistent nonvalvular atrial fibrillation (AF). MATERIALS AND METHODS: We
      studied 67 patients (W/M: 23/44; mean age 63.2 +/- 7.1 years) with persistent AF
      lasting longer than 1 month. Rate control strategy targeted resting heart rate 70
      90/min. All study subject underwent ETT in order to assess their exercise
      capacity. Before ETT we performed TTE in all patients and calculated the area of
      LA (LAar), longitudinal and saggital diameter of LA (LAlax, LAsax), LV end
      diastolic diameter (LVEDD) and LV shortening fraction (FS). TTE was performed
      again in 2 and 12 months after beginning of observation. RESULTS: Using variation
      analysis we established the correlation between time of ETT in patients with
      persistent AF and dynamics of change of specific echocardiographic parameters in
      12 months follow-up. In patients with ETT time <60 sec we observed statistically
      significant rise of LAar from 26.5 +/- 6.1 to 29.6 +/- 4.9 cm2 (p < 0.05; ANOVA)
      and deterioration of LV function assessed with FS from 35.6 +/- 5.3% on the
      beginning to 31.7 +/- 7.4% at the end of study (p < 0.02; ANOVA). There was no
      correlation between time of ETT and dynamics of change of other echocardiographic
      parameters in patients with time of ETT >60 sec. CONCLUSIONS: Time of exercise
      tolerance test limited with heart failure symptoms is an independent factor
      predicting dynamics of change of chosen echocardiographic parameters of left
      heart in long-term observation of patients with persistent atrial fibrillation.

PMID- 16789519
TI  - [Concentration of elements in plasma of patients with essential hypertension].
AB  - Disturbances in macro- and microelements composition may play a significant role
      in the development of essential hypertension. The aim of the study was to
      estimate main and trace elements concentration in plasma of hypertensive
      patients. The study involved 150 subjects, aged 33-60 years, who were allotted
      into 2 groups: I--50 clinically healthy subjects (controls), II--100 patients
      with arterial hypertension. Age and sex ratio were similar in the examined
      groups. Those subjected to the study were not administered any drugs at least 3
      months prior to the determination of macro- and microelements. Determinations of
      trace elements Ca, F, Na, K, Mg, Fe, Zn, Cu, Ni, Mo, Al, Cd, Fb, Mu, Se, Cr, Co,
      Li, V, B, Ba, were performed with atomic emission spectrometer with plasmic
      excitation (ICP MS Philips PU). In group II in comparison to group I (controls)
      higher values of Fe, Pb, Al, Cd, Co, B i Ba were observed, as well as higher
      Zn/Cu ratio; but lower values of Cu and lower Ca/Pb, Ca/Al, Zn/Fe, Se/Fe, Zn/Al,
      Zn/Cd, Se/Pb, Se/Al, Se/Cd ratio. Increase of prooxidative and decrease,of
      antioxidative elements in plasma may significantly contribute to the essential
      hypertension pathogenesis probably through oxidative stress development.

PMID- 16789520
TI  - [Usefulness of continuous glucose monitoring system in detection of hypoglycaemic
      episodes in patients with diabetes in course of chronic pancreatitis].
AB  - BACKGROUND: Recently introduced method of glucose monitoring--Continuous Glucose
      Monitoring System (CGMS, Medtronic MiniMed) now offers new possibilities of
      assessing metabolic control of diabetes as it records blood glucose values 288
      times per day. CGMS is particularly helpful in pancreatogenic diabetes, which is
      associated with essentially poor metabolic control and higher number of
      hypoglycemic events. AIM: The study aimed at assessing number of hypoglycemic
      episodes, including symptom-free hypoglycemic episodes detected with CGMS and
      glucose meter (GM). TURESTIGALED GROUP AND METHODS: The study comprised 60
      diabetic out-patients, treated with insulin in age mean 53.8 +/- 5.1 years, with
      chronic pancreatitis lasting mean 10.6 +/- 4.6 years and diabetes mellitus-- 4.9
      +/- 2.4 years. Serum glucose concentration values were measured with the use of
      CGMS. Ten measurements of capillary blood glucose concentration with GM were
      performed daily during the period of CGMS use. Observation period of hypoglycemic
      episodes lasted 3 days. Hypoglycemic event was detected when glucose value
      decreased below 60 mg/dl. The number of hypoglycemic episodes, including symptom
      free hypoglycemic episodes detected with CGMS and GM was compared. RESULTS:
      Number of hypoglycemic events detected with CGMS was five times higher than in GM
      measurements (p < 0.001). Episodes of symptom--free hypoglycemia were noted in
      CGMS six times higher than in GM measurements (p < 0.001). Hypoglycemia was found
      in twice as many patients when diagnosed upon CGMS results as when found upon GM
      results (p < 0.01). Episodes of symptom-free hypoglycemia were detected in six
      times as many patients when diagnosed upon CGMS as when analysed upon GM
      measurements (p < 0.001). CONCLUSION: CGMS offers more complete data on low blood
      glucose incidents, including symptom-free hypoglycemia, than intensive blood
      glucose monitoring with the use of glucose meter.

PMID- 16789521
TI  - [Diagnostics of viral respiratory infections in hospitalized patients and
      ambulatory patients from SENTINEL program during 2004/05 season in Poland].
AB  - The aim of the study was to evaluate an impact of respiratory infections on the
      study population, type/subtype of influenza viruses circulating during 2004/05
      season within the groups of hospitalised (n=35) and ambulatory patients (n=420)
      and to determine antigenic affinity of isolated viral strains. Laboratory
      diagnostics of influenza A and B type, RSV, adenovirus and parainfluenzavirus
      (type 1, 2 and 3) was performed using direct immunofluorescence test (DIFA),
      virus isolation on MDCK cell line and RT-PCR assay. Respiratory viruses were
      detected in about half of hospitalised patients and one fifth of ambulatory
      patients. Within these groups more than 80% hospitalised patients and 70%
      ambulatory patients were infected with influenza virus. Two influenza A subtypes
      (H3N2) and (H1N1) and B type were detected. Influenza ranged from 68,8% (26-45
      age group) to 89,5% (15-25 age group) of all laboratory confirmed respiratory
      infections, only among the youngest children (0-3 years old) one fourth of
      infections was caused by influenza virus and in 50% samples RSV was detected.
      Influenza virus was also present in over 80% positive samples from hospitalised
      patients over 65 years old. Sensitivity of RT-PCR compared to other influenza
      diagnostic methods was 95% and specificity was > or = 99%. Fast and accurate
      influenza diagnostics using molecular biology methods enables implementing
      therapy with the new generation antivirals (neuraminidase inhibitors), that are
      effective only when administered up to 36-48 h from onset of the illness. In
      diagnostics of other. respiratory viruses it is necessary to apply more sensitive
      diagnostic methods e.g. multiplex RT-PCR. Influenza isolates were
      A/Wyoming/3/2003-like, B/Hong Kong/330/2001-like, A/New Caledonia/20/99-like and
      B/Jiangsu/10/2003-like strains that were components of influenza vaccines for
      2003/04 and/or 2004/05 seasons. Annual vaccination remains the best way to
      prevent infection in high risk populations. Costs of influenza vaccine and
      oseltamivir prophylaxis in our country are on average respectively fifty and five
      times lower than each day of patients' stay at an intensiv care unit. Every year
      within the confines of global surveillance programs (e.g. SENTINEL), there are
      monitored circulating influenza viruses, in order to define vaccine composition
      for the next season and identify new and potentially pandemic strains.

PMID- 16789522
TI  - [Femoral artery pseudoaneurysms: treatment with ultrasound guided thrombin
      injection in 28 patients].
AB  - INTRODUCTION: Femoral artery pseudoaneurysms (PSA) develop in 0.2-8% patients
      undergoing procedures that require femoral artery cannulation. Ultrasound guided
      thrombin injection has been described as successful and safe alternative to
      ultrasound guided compression and surgical treatment. AIM OF THE STUDY:
      Assessment of efficacy and safety of PSA treatment with USGTI. METHODS: 28
      patients (pts) (18 female, mean age 64.6 +/- 11.4) with femoral pseudoaneurysms
      developed due to coronary angiogram or percutaneous coronary angioplasty were
      treated with ultrasound guided thrombin injection. 24 PSAs arose from right
      common femoral artery, 3 from right superficial femoral artery, and 1 from left
      common femoral artery. 24 patients were receiving antiplatelet and 4
      anticoagulation therapy at the time of the procedure. With ultrasound guidance, a
      21Gx11/2 needle was placed into pseudoaneurysm lumen followed by thrombin
      injection (1074 +/- 473 U). No complications of the procedure were observed. In
      24-hour observation USGTI was successful in 28 (100%) patients. However, in 7-day
      follow-up resolution of 1 PSA was found, which reduced efficacy rate to 96.3%.
      CONCLUSIONS: Ultrasound guided thrombin injection is a successful, safe and well
      tolerated method of pseudoaneurysms treatment. Neither antiplatelet nor
      anticoagulation therapy affects success rate of the method.

PMID- 16789523
TI  - [Transient pancytopenia due to ticlopidine--a case report].
AB  - Transient pancytopenia as an adverse hematologic reaction due to ticlopidine. We
      present a case of transient pancytopenia due to ticlopidine in 66-year-old woman
      who was administrated with ticlopidine as a primary prevention of heart failure.
      The first sign was a skin rush which was followed by ticlopidine cessation. Two
      days later she developed septic shock, pneumonia and neutropenia (600 cells/mm3)
      with decrease of platelats, erytrocytes count and hemoglobin. Blood transfusions
      were not required. After treatment with antibiotics according to antibiogram the
      patient recovered and was dismissed after 38 days with normal blood morphology.
      We conclude that ticlopidine was the most probable cause of transient
      pancytopenia. Severe adverse hematological effects due to ticlopidine occur in
      0.8-2.3% cases. Thus treatment with ticlopidine should be cerfully considered.

PMID- 16789524
TI  - [Normoaldosterone spironolactone sensitive hypertension--a case report].
AB  - We report the case of normoaldosterone spironolactone sensitive hypertension.
      Patients suffering from this recently identified form of arterial hypertension
      exhibit clinical symptoms resembling the symptoms of primary aldosteronism. The
      described disturbances may be misdiagnosed as essential hypertension because
      plasma aldosterone levels and aldosterone/renin ratio in patients are within the
      normal ranges. In the described state of the examined female, detection of the
      disease and implementation of spironolactone treatment not only normalised
      arterial blood pressure but also allowed to avoid unnecessary administration of
      many antihypertensive agents.

PMID- 16789525
TI  - [Hepatorenal syndrome. Cases report].
AB  - The hepatorenal syndrome is defined as renal failure in patients with severe
      liver disease. It may be diagnosed by exclusion of other potential factors which
      may cause renal failure, such as hypovolaemia, nephrotoxic drugs and severe
      bacterial infection. Liver transplantation is the target treatment leading to
      recovery of renal function. Other methods such as vasoconstrictors, renal
      replacement therapy and repeated paracenthesis with intravenous albumin infusions
      are also presented.

PMID- 16789526
TI  - [Ethanol metabolism in pancreas and its role in alcoholic pancreatitis].

PMID- 16789527
TI  - [The influence of physical exercise upon immunological system in humans].

PMID- 16789528
TI  - [Thyrotoxicosis and the cardiovascular system--selected pathophysiological
      aspects].

PMID- 16789529
TI  - [Chronic obstructive pulmonary disease exacerbation--effects on quality of life].

PMID- 16789530
TI  - [Primary hyperparathyroidism].

PMID- 16789531
TI  - [Genetic factors in the pathogenesis of chronic obstructive pulmonary disease].

PMID- 16789532
TI  - [Current therapy for multiple myeloma].

PMID- 16789533
TI  - [The assessment of the patient with systemic sclerosis clinical course of the
      EUSTAR Budapest, January 13-16, 2005].

PMID- 16789534
TI  - [The principles, criteria, and methods of evaluation of health hazards associated
      with short-term exposure to chemical atmospheric air pollutants].
AB  - The authors discuss the basic concepts of a system developed to evaluate health
      hazards associated with short-term exposure of different population groups to
      inhaled chemicals, including exposure that takes place in emergency situations.
      The article contains examples of acute exposition profiles for the most wide
      spread air pollutants, such as nitrogen dioxide, ozone, sulfur dioxide, and
      carbon monoxide, developed using quantitative values of short-term exposure risk
      criteria.

PMID- 16789535
TI  - [Atmospheric air pollution and population mortality in Russian Federation
      regions].
AB  - Regularly published national reports on population health in Russian Federation,
      based on the results of statistic analyses and the data from hygienic and
      epidemiological studies, demonstrate associations between exposure to hazardous
      environmental factors and population morbidity. Research into correlations
      between exposure to such factors and population health status using extensive
      databases, makes it possible to obtain statistically significant results and put
      forward hypotheses for epidemiological studies. The aim of this research was to
      study the levels and dynamics of population mortality, and atmospheric air
      condition, as well as correlations between them in regional centers of Russian
      Federation. The study covers the period from 1985 through 1998.

PMID- 16789536
TI  - [Complex characterization of the influence of environmental factors and social
      conditions on population health].
AB  - The study determined the overall contribution of atmospheric air pollution and
      socioeconomic and other factors on population health, as well as the role of
      medical providence in the lowering of population morbidity. The study shows that
      different individual factors of medical providence have different effects on
      medicodemographic situation. Also different is the significance of various
      characteristics of socioeconomic conditions. The results demonstrate that the
      contribution of air pollutants and their mixtures into male and female mortality
      in various age groups is different and depends on the cause of death and
      pathogenetic peculiarities of the action of the components.

PMID- 16789537
TI  - [Dependence of demographic indices on environmental and hygienic factors in
      Kazakhstan].
AB  - The authors demonstrate the hygienic significance of Gompertc-Makeham model,
      which expresses age-dependent mortality of population, and use both theoretical
      concepts and statistical data to substantiate a hypothesis of an indicator
      significance of the model's free coefficient for environmental state evaluation.
      The model was approved using the data from the regions of Republic Kazakhstan.

PMID- 16789538
TI  - [The ecologo-hygienic problem of soil pollution].
AB  - The article covers the ecologo-hygienic aspects of anthropogenic soil pollution,
      and important directions of research into its sanitary protection. The authors
      adduce data concerning the levels of actual soil pollution with chemicals and
      biological agents (microbiological and helminthological ones) in various centers
      of population, and discuss the variants of solving the ecologo-hygienic problems
      of soil protection in Russian Federation.

PMID- 16789540
TI  - [The role of dwelling environment in human health].
AB  - The authors adduce the ecologo-hygienic characterization of the most significant
      dwelling environmental factors, such as chemical air pollution, microclimatic
      parameters, biological pollution, noise, electromagnetic fields, light, etc. They
      have developed a conception of providing ecologo-hygienic dwelling safety.

PMID- 16789539
TI  - [Topical problems of society's waste handling].
AB  - The fact that the volume of waste steadily grows, makes its handling one of the
      most topical scientific, technical, and socioeconomic problems in the world. The
      article covers important ecological and hygienic problems of waste handling and
      the effects of waste of human health.

PMID- 16789541
TI  - [The effects of fungous semination of dwelling environment on the cytological
      status of human mucosal membranes].
AB  - High level of fungous semination of dwelling environment is shown to have a
      destructive effect on mucosal membranes, which is manifested by their
      inflammation and allergic condition. The study of the cytological status of the
      nasal and oral mucosa proved its high sensitivity and significance when studying
      the influence of fungous semination of dwelling environment on the human
      organism.

PMID- 16789542
TI  - [Comparison of the methods of evaluation of the microbiological danger of
      antimicrobial agents by the example of oligo- and polyguanidines].
AB  - The article contains the results of comparison of the methods of evaluation of
      the microbiological danger of antimicrobial agents by the example of oligo- and
      polyguanidines. The study demonstrates that choice of an adequate study model (a
      bacterial or protozoa species) and exposure time depends on the characteristics
      of the preparation to be tested. It shows that the microbocide activity of
      polyguanidines should be studied on a bacterial model using long (24 hours)
      exposure. The most sensitive to XG6 was a protozoa culture in short-time
      exposure. To evaluate the biological danger ofantimicrobial agents, it is also
      possible to apply techniques that allow revealing reversable physiological
      changes in a culture of test objects.

PMID- 16789543
TI  - [The prospects of application of methods of population immune status evaluation
      when performing mass hygienic studies].
AB  - Non-invasive methods of sampling and a range of immunological assays for mass
      ecologo-hygienic studies of population were developed and introduced into
      practice in Sysin Scientific Research Institute of Human Ecology and
      Environmental Hygiene of Russian Academy of Medical Sciences. The studied
      materials were saliva, urine, breast milk, the condition of lymph nodes, and
      anamnesis. The complex of non-invasive methods was shown to be less complicated
      and, at the same time, informative and cheap, which allows recommending it for
      sociohygienic monitoring when performing mass hygienic studies.

PMID- 16789544
TI  - [Risk factors of allergopathy].
AB  - This review contains a detailed description of factors which determine the
      allergic danger in a region, the sources of allergens entering the environment,
      and classification of allergens according to their origin and ecological
      significance. The authors draw attention to the existing criteria of
      allergopathic conditions, which may serve as an important diagnostic index when
      establishing sensitization and performing specific diagnostics of allergic
      diseases. The article covers a complex of laboratory diagnostic methods, directed
      towards timely detection of allergopathology and its prevention.

PMID- 16789545
TI  - [The microbiological safety of food products, and environmental factors].
AB  - The author of the review analyzes the mechanisms of changes of biological
      properties of microorganisms causing alimentary infections and intoxications. A
      complex of environmental factors, such as anthropogenic, technogenic, social,
      ecological, and climatic ones, are considered to be the main cause of these
      changes. Food contamination by microorganisms and their toxins is facilitated by
      climatic warming. The exposure of consumers to food toxins grows, and alimentary
      infections become more frequent. New classes of alimentary infections have
      appeared; clinical manifestations and complications of food-related infections
      have become more serious. Besides, the quality and value of food products may be
      reduced by lactic acid microorganisms and moulds, whose content in food chains
      increases due to warming, especially in regions with a high anthropogenic load.
      From the economic perspective, the behavior of microbial food contaminants under
      the conditions of climatic warming increase direct losses of agricultural
      products due to their lesion by microscopic fungi, mycotoxins etc., as well as
      spoilage microflora. This may result in food shortage and famine in distant
      regions. The article covers control measures and the management of
      microbiological risks under the condition of climatic warming.

PMID- 16789546
TI  - The excellence of Aomori Hiba (Hinokiasunaro) in its use as building materials of
      Buddhist temples and Shinto shrines.
AB  - Five hinokitiol-related compounds (hinokitiol (beta-thujaplicin), beta-dolabrin,
      gamma-thujaplicin, 4-acetyltropolone and alpha -thujaplicin) isolated from the
      acid oil of Aomori Hiba (Thujopsis dolabrata Sieb. et Zucc. var hondai MAKINO)
      showed clear antifungal activity against wood-rotting fungi. These compounds have
      obvious insecticidal effects on termites. They also exhibited potent acaricidal
      activity against mites. The above-mentioned features suggest that Konjiki-do, a
      well known national treasure, one of the buildings in Chuson-ji Temple of Iwate
      Prefecture, Japan, which was built of wood from the tree containing these five
      compounds, was kept from harm against noxious insects and wood-rotting fungi for
      a long time of about 840 years, until it was extensively repaired in 1962. In
      addition to Konjiki-do, there are some old famous Buddhist temples and Shinto
      shrines using Aomori Hiba. From the results, it was found that Aomori Hiba
      (Hinokiasunaro) is excellent for use as building materials.

PMID- 16789547
TI  - Morphological significance of cladosporium contaminants on materials and utensils
      in contact with food.
AB  - Cladosporium contaminants on materials and utensils that come into contact with
      food were morphologically investigated. The most common contaminants, C.
      cladosporioides and C. sphaerospermum, were detected on the samples. The
      morphological changes of the Cladosporium species were investigated by using
      stereoscopic, optical light, fluorescent, and scanning electron microscopes.
      Microscopically the Cladosporium contaminants were observed as aggregated dark
      brown spots, strongly pigmented, irregularly swollen, and in long chains. Using
      fluorescent microscopy, the Cladosporium mycelia were clearly stained with
      fluorescein diacetate as viable cells, but the old cells were mostly non-viable,
      as shown by staining with propidium iodide. The dynamics of the morphological
      changes showed that the penetrating mycelia were closely attached to the surface
      of the materials and utensils under investigation. These results provide
      information about the significance of Cladosporium contamination on materials and
      utensils in contact with food and may contribute to the control of fungal
      contamination.

PMID- 16789548
TI  - Cleanability of stainless steel surfaces as influenced by heat treatment.
AB  - The cleanability of heat-treated 316L stainless steel particles treated at
      various temperatures of 100 to 500 degrees C was studied in a plug-flow column
      fed by a 0.1M NaOH solution. Bovine Serum albumin (BSA) was used as the model
      fouling agent. Heat treatment resulted in the enrichment of iron in passive films
      on stainless steel particles depending on temperature. The degree of surface
      hydroxylation and the apparent surface charge density (sigma(app)) of stainless
      steel particles decreased markedly with increasing heating temperatures. The
      saturation amounts of BSA adsorbed (gamma(sat)) were larger on the particles
      heated at higher temperatures. No correlation was observed between the gamma(sat)
      and sigma(app) values. With increasing heating temperatures, the rate of BSA
      desorption from stainless steel particles decreased gradually in the initial and
      later stages of cleaning, resulting in larger amounts of BSA remaining on the
      particles at the end of 120-min of cleaning. The susceptibility to BSA adsorption
      and the cleanability were found to be correlated with the iron content of the
      passive films on stainless steel particles. It could be suggested that the
      decrease in the cleanability was probably due to the formation of iron-enriched
      passive films with lower degrees of surface hydroxylation of stainless steel
      particles due to heat treatment.

PMID- 16789549
TI  - Enhanced antifungal effect of the selective medium for the detection of
      Legionella species by a combination of cycloheximide, amphotericin B and
      thiabendazole.
AB  - The accurate detection of Legionella from environmental water samples using
      conventional plate culture methods is often made difficult by the overgrowth of
      non-target microorganisms on the selective agar plates. Acid pretreatment is a
      very effective pretreatment to decrease the overgrowth of heterotrophic bacteria.
      However, acid pretreatment would not be expected to eliminate molds. We evaluated
      the effects of four kinds of antifungal agents, individually and in combination,
      on the growth of Legionella strains and molds. Consequently, it was demonstrated
      that the combination of cycloheximide, amphotericin B and thiabendazole was very
      effective in eliminating molds on agar plates, and resulted in the improved
      detection of Legionella. Examination of 214 cooling tower water samples using the
      enhanced antifungal selective medium (CAT alpha) instead of GVPC alpha selective
      medium demonstrated a decrease in contamination by molds from 13.6% to 1.9%
      without affecting the growth of Legionella.

PMID- 16789550
TI  - Combined use of the biocontrol bacterium Pseudomonas fluorescens strain LRB3W1
      with reduced fungicide application for the control of tomato Fusarium wilt.
AB  - Pseudomonas fluorescens strain LRB3W1 inhibited the mycelial growth of Fusarium
      oxysporum f. sp. lycopersici and suppressed the Fusarium wilt of tomato. The
      chemical fungicide, benomyl, did not suppress the disease incidence at low
      concentrations. However, the disease incidence was decreased by the combined
      application of benomyl at low concentrations with strain LRB3W1. Combined
      application of benomyl with the bacterium was more effective than treatment with
      the bacterium alone. The survival of strain LRB3W1 was not influenced by the
      presence of benomyl. This combined use of the biocontrol bacterium, strain
      LRB3W1, and a fungicide, benomyl, should be an attractive approach for
      suppressing tomato wilt.

PMID- 16789551
TI  - Growth characteristics of fusants by protoplast fusion between the thermotolerant
      yeast, Kluyveromyces marxianus, and the starch-assimilating yeast, Schwanniomyces
      occidentalis.
AB  - Intergeneric fusants were obtained by protoplast fusion between the
      thermotolerant yeast, Kluyveromyces marxianus, and the starch-assimilating yeast,
      Schwanniomyces occidentalis. Two thermotolerant fusants growing at 40 degrees C
      were screened on the medium containing soluble starch. These fusants showed weak
      growth in a soluble starch medium and the production of a little amylase. The
      carbon source assimilation and the chromosome composition of the fusants were
      similar to those of the K. marxianus parent. However, a chromosomal difference
      from K. marxianus was recognized in the fusants. These results show the
      possibility that the fusants are amylase-producing strains rearranged from K.
      marxianus.

PMID- 16789552
TI  - Characteristics of the inactivation of Escherichia coli by infrared irradiative
      heating.
AB  - The inactivation of Escherichia coil by infrared (IR) irradiation was
      quantitatively evaluated and compared to that by thermal conductive heating.
      After the bulk temperature of the sterile saline irradiated by IR reached a
      steady given temperature, the E. coil culture was inoculated and IR heating was
      conducted. A mullite cylinder FIR heater, of which main wavelength is 4-7 microm,
      was used for IR heating. The killing of the E. coil by IR heating and thermal
      conductive heating both followed first-order reaction kinetics, and the apparent
      death rate constants (k) under different conditions were obtained. At the same
      temperatures, pasteurization by IR heating was more effective than that by
      thermal conductive heating, and its effectiveness increased with a decrease in
      liquid layer thickness. The values of k due to IR heating were approximately 2-3
      times and one order larger than those due to thermal conductive heating at the
      liquid layer thickness of 10 mm and 1.5 mm, respectively. The activation energy
      (Ea) for the killing of E. coli by IR irradiation was slightly lower than that by
      thermal conductive heating, indicating that there are some differences in the
      action mechanisms.

PMID- 16789560
TI  - I am a nurse.

PMID- 16789561
TI  - Leadership, innovation and knowledge workers in health-care reform.

PMID- 16789562
TI  - Empowerment and shared leadership: A conversation with Deborah Tamlyn.

PMID- 16789563
TI  - Toward 2020: visions for nursing setting the stage for the future.

PMID- 16789565
TI  - The mid-career nurse: what now?

PMID- 16789564
TI  - Highlights from the 2005 Canadian Nurses Association Annual Report.

PMID- 16789566
TI  - Adherence to antihypertensive therapy.

PMID- 16789567
TI  - Conduit to excellence. Interview by Barabara Sibbald.

PMID- 16789568
TI  - How do you care for a patient with a cancer you have never seen before?

PMID- 16789570
TI  - ONS members participate in the nurse in Washington Internship Program.

PMID- 16789571
TI  - "Pay for performance" programs are on the not-so-distant horizon.

PMID- 16789572
TI  - ONS adopts governance best practices to ensure integrity.

PMID- 16789573
TI  - Nurses, make your voice heard on scope of practice issues.

PMID- 16789574
TI  - Nursing education in peril.

PMID- 16789575
TI  - What should I say? Talking with patients about sexuality issues.

PMID- 16789576
TI  - Stress, fears, and phobias: the impact of anxiety.

PMID- 16789577
TI  - Dyspnea.

PMID- 16789578
TI  - The state of the science on nursing approaches to managing late and long-term
      sequelae of cancer and cancer treatment.

PMID- 16789579
TI  - Part I: regional chematherapy clinical studies in nontraditional clinical
      settings.

PMID- 16789580
TI  - Part II: Nursing implications of administering chemotherapy in interventional
      radiology or the operating room.

PMID- 16789581
TI  - Ketoconazole as a secondary hormonal intervention in advanced prostate cancer.

PMID- 16789582
TI  - Family Systems genetic Illness Model--breast cancer.
AB  - Mrs. R and others like her are having prophylactic surgery to prevent breast
      cancer based primarily on their family history, personal history, and
      environmental risks. Although the clinical application of genetics medical
      research is in its infancy, its relevance to breast cancer already is making
      significant I advances toward more accurate prognosis and treatment options for
      women and their families. Illness and death from breast cancer continue to limit
      human existence, whereas new information and medical treatments increase the
      complexity of healthcare decisions and family life. Rolland and Williams' (2005)
      FSGI Model helps nurses and advanced practice nurses understand how illnesses
      such as breast cancer likely will affect patients' lives and families, well
      before any biologic markers are detectable. Considering the complexity of medical
      information that currently is available and the risks involved in genetic testing
      for breast cancer, the best recommendation at this time for people with a family
      history of breast cancer is to see a genetics counselor. Nurses can help
      individuals and families prepare for counselors by giving them a list of helpful
      questions and recommending that they bring a trusted family member or confidant
      to the meeting. For women who decide to have prophylactic breast surgery, nurses
      play a significant role in helping them prepare for the emotional and physiologic
      ramifications. The FSGI Model anticipates the time when families will have an
      overall genetic risk profile, which can guide them in their prevention efforts
      and truly give them informed consent.

PMID- 16789583
TI  - Hematopoietic support with moderately myelosuppressive chemotherapy regimens: a
      nursing perspective.

PMID- 16789585
TI  - Impact of direct-to-consumer advertising on healthcare providers and consumers.

PMID- 16789584
TI  - Failure mode and effect analysis: a technique to prevent chemotherapy errors.
AB  - Complex, multidrug chemotherapy protocols commonly are administered to patients
      with cancer. At every step of the chemotherapy administration process, from the
      point that chemotherapy is ordered to the point that it is infused and beyond,
      potential for error exists. FMEA, a proactive process that promotes systematic
      thinking about the safety of patient care, is a risk analysis technique that can
      be used to evaluate the process of chemotherapy administration. Error prevention
      is an ongoing quality improvement process that requires institutional commitment
      and support, and nurses play a vital role in the process.

PMID- 16789586
TI  - Reading a research article part III: the data collection instrument.
AB  - Parts I through III of this series of articles gave an introduction to some of
      the issues requiring attention when performing clinical studies and summarizing
      the results statistically as well as clinically. Statistical methods have been
      described for the identification of statistically significant differences and
      associations between an experimental group and a control group or over the course
      of time after an intervention. The next article will address the methods used for
      the determination of the strength or magnitude of these identified statistically
      significant differences.

PMID- 16789587
TI  - Presentation of self. Generalist or specialist?

PMID- 16789588
TI  - MAOI antidepressant drugs.

PMID- 16789589
TI  - Active living for healthy youth.

PMID- 16789590
TI  - From the streets to assisted living: perceptions of a vulnerable population.
AB  - The rapid growth of assisted-living facilities is paralleled by the necessity to
      understand the needs of the people living in them. A hallmark challenge for
      individuals who are poor and disabled, and often marginalized from mainstream
      society, is maintaining integrity and being a whole person, rather than a sum of
      broken parts. A key to maintaining this integrity is the ability to find stable
      housing and support systems. The inner-city assisted-living facility in this
      study is unique in that all of its residents are funded by Medicaid. The
      residents have complex needs related to histories of homelessness, mental
      illness, drug and/or alcohol addiction, and chronic illness. The purpose of this
      study was to explore the needs of this vulnerable population as they adapt to a
      new home and a new concept of assisted, yet independent, living. Structured
      interviews with key informants and oral survey questionnaires with residents
      provided quantitative and qualitative data about physical and mental health
      status, social support, perception of control, psychological wellbeing, and life
      satisfaction. This study provided valuable insights into the challenges inherent
      in providing a high quality of life in assisted living for a vulnerable
      population with diverse needs.

PMID- 16789591
TI  - Cameras and community health.
AB  - Photography projects are an alternative teaching method that can be easily
      integrated into community programs with adolescents and children. This article
      provides a brief review of the use of photography in documenting social and
      health issues. Two examples of community photography projects with easily ignored
      populations are described. These projects gave a voice to participants and
      allowed them to demonstrate their creativity with cameras. An implementation
      guide is presented to provide concrete suggestions for implementing community
      photography projects.

PMID- 16789592
TI  - Borderline personality disorder: nursing interventions using dialectical
      behavioral therapy.
AB  - Psychotherapeutic treatment of people with borderline personality disorder (BPD)
      is one of the greatest challenges confronting mental health professionals today.
      Clients with BPD are often difficult for nurses to work with, perhaps due to a
      lack of understanding of the underlying dynamics of the disorder. This article
      describes effective treatment strategies for BPD with a central focus on
      dialectical behavioral therapy (DBT). In typical mental health settings, nurses
      can effectively implement interventions using the concepts of DBT to help people
      with BPD build effective coping strategies and skillful behavioral responses for
      improved quality of life.

PMID- 16789593
TI  - Walking tall: a person with schizophrenia on a journey to better health.

PMID- 16789594
TI  - [Reflections on the Nobel prize, the Helicobacter pylori, the peptic ulcer and
      the scientific paradigms].

PMID- 16789595
TI  - [Mortality-associated factors in major surgery: retrospective analysis in a
      referral center].
AB  - BACKGROUND: There are very few studies that analyze surgical morbidity and
      mortality in the general population and the factors associated with those events.
      OBJECTIVE: To determine factors associated to mortality in surgical procedures
      performed in a tertiary referral center in Mexico City. METHODS: We
      retrospectively analyze surgical mortality in 4,157 consecutive surgical
      procedures performed in a one-year period from 1/1/2000 through 12/31/2000.
      Categorical variables were analyzed with the chi-square test and continuous
      variables with the t-Student test. Significance was defined as p < 0.05. RESULTS:
      During the study period there were 76 postoperative deaths, representing a
      mortality rate of 1.82%. Mean patient's age in the entire cohort was 48.7 +/-
      17.6 years and for the patients who died in the postoperative period 57.8 +/-
      17.8 years (p < 0.05). Sixty-six percent of deaths were attributed to the primary
      or surgical disease. In 33.8% of postoperative deaths an adverse event was
      identified as responsible for the outcome. In 23% of cases there was a
      potentially preventable event, representing 0.3% of surgical procedures. Most
      patients (96.9%) had at least one comorbid condition and 61.5% had two or more.
      Almost 80% of surgical deaths occurred in patients with ASA score III of IV and
      albumin levels below 3.5 g/dL. Most common cause of death was sepsis, reported in
      35% of patients who died in the postoperative period. CONCLUSION: Surgical
      mortality in our series is low. In 0.3% of procedures it was detected a
      potentially preventable event. Postoperative deaths occurred in older patients
      with low albumin levels.

PMID- 16789596
TI  - [Precision and accuracy of "a pocket" pulse oximeter in Mexico City].
AB  - BACKGROUND: Pulse oximeters are frequently used in the clinical practice and we
      must known their precision and accuracy. The objective was to evaluate the
      precision and accuracy of a "pocket" pulse oximeter at an altitude of 2,240 m
      above sea level. METHODS: We tested miniature pulse oximeters (Onyx 9,500, Nonin
      Finger Pulse Oximeter) in 96 patients sent to the pulmonary laboratory for an
      arterial blood sample. Patients were tested with 5 pulse oximeters placed in each
      of the fingers of the hand oposite to that used for the arterial puncture. The
      gold standard was the oxygen saturation of the arterial blood sample. RESULTS:
      Blood samples had SaO2 of 87.2 +/- 11.0 (between 42.2 and 97.9%). Pulse oximeters
      had a mean error of 0.28 +/- 3.1%. SaO2 = (1.204 x SpO2) - 17.45966 (r = 0.92, p
      < 0.0001). Intraclass correlation coefficient between each of five pulse
      oximeters against the arterial blood standard ranged between 0.87 and 0.99. HbCO
      (2.4 +/- 0.6) did not affect the accuracy. CONCLUSIONS: The miniature oximeter
      Nonin is precise and accurate at 2,240 m of altitude. The observed levels of HbCO
      did not affect the performance of the equipment. The oximeter good performance,
      small size and low cost enhances its clinical usefulness.

PMID- 16789597
TI  - Second allogeneic peripheral blood stem cell transplants with reduced-intensity
      conditioning.
AB  - In two institutions in Mexico, twelve patients were given a second allogeneic
      stem cell transplantation, using the "Mexican" non-myeloablative preparative
      regimen. Eight had a malignant condition (six acute leukemias, one myelofibrosis
      and one myelodysplasia), eleven individuals were allografted twice from the same
      donor and in one case, cells from two different umbilical cords were used. The
      median time to conduct the second allograft after the first one was 6 months
      (range 1-41). The five patients who failed to engraft after the first transplant
      failed also to engraft after the second one; all of them had been heavily
      transfused. Only three patients were successfully rescued with the second
      transplant, two with acute leukemia and one with aplastic anemia. Seven patients
      are alive 10-41 months (median 35) after the second transplant, but only three
      (25%) remain disease-free. The 52-month overall survival (SV) of the patients is
      58%, whereas the median overall SV has not been reached, being above 52 months.
      Conducting a second allograft may be useful to rescue some individuals relapsing
      after a first hematopoietic allotransplant.

PMID- 16789598
TI  - [ACE gene polymorphism correlation (I/D) with the ventricular function in
      patients with ischemic and idiopathic dilated cardiomyopathy].
AB  - Dilated cardiomyopathy is a myocardial disease, characterized by biventricular
      expansion. Renin-angiotensin-aldosterone system (RAAS) is closely related with
      the progress of this pathology. Has been shown that angiotensin converting enzyme
      (ACE) gene insertion/deletion (I/D) polymorphism influences as much in the
      plasmatic concentration as in activity of ACE. In addition, ACE IID polymorphism
      has been associated with remodeling phenomena and an increased risk to develop
      several cardiovascular diseases. On virtue of the influence of ACE gene
      polymorphism on RAAS, we studied the correlation between ACE I/D polymorphism
      with morphologic and functional clinical alterations in ischemic or idiopathic
      dilated cardiomyopathy in one attempt to establish its utility as prognosis
      factor. METHODS AND RESULTS: We studied 30 patients of The National Institute of
      Cardiology. Ventricular function was evaluated by transthoracic echocardiography.
      ACE genotype was determined by polymerase chain reaction (PCR). Results for left
      ventricle shown: Tei Index was increased in patients with II genotype (0.84 vs.
      0.48) when were compared to patients with DD genotype p < 0.01. Eccentricity
      Index was lesser in the group with II genotype (0.64), than in the group DD
      (0.86) p < 0.01. Ventricular mass was increased in DD patients when was compared
      with II group (174 g vs. 133 g) Isovolumetric contraction time was shorter in
      group DD than in II (45 mseg vs. 139 mseg) p < 0.05. These findings denote better
      preservation of left ventricular function in patients with DD genotype. In
      opposition, right ventricle shown an increased Tei Index in the group with DD
      genotype (1.01) when was compared with II genotype (0.55), p < 0.05. Pulmonary
      artery systolic pressure tended to be higher in DD genotype group without reach
      statistic significance. CONCLUSIONS: In our group of study, patients with DD
      genotype shown better left ventricular function in ischemic or idiopathic dilated
      cardiomyopathy. On the opposite right ventricular function were more deteriorated
      in patients with ACE DD genotype.

PMID- 16789599
TI  - Proteins in a DNA world: expression systems for their study.
AB  - Every day, new proteins are discovered and the need to understand its function
      arises. Human proteins have a special interest, because to know its role in the
      cell may lead to the design of a cure for a disease. In order to obtain such
      information, we need enough protein with a high degree of purity, and in the case
      of the human proteins, it is almost impossible to achieve this by working on
      human tissues. For that reason, the use of expression systems is needed.
      Bacteria, yeast, animals and plants have been genetically modified to produce
      proteins from different species. Even "cell-free" systems have been developed for
      that purpose. Here, we briefly review the options with their advantages and
      drawback, and the purification systems and analysis that can be done to gain
      understanding on the function and structure of the protein of interest.

PMID- 16789600
TI  - [Molecular basis of cancer].
AB  - Cancer is a group of diseases characterized by an autonomous proliferation of
      neoplastic cells which have a number of alterations, including mutations and
      genetic instability. Cellular functions are controlled by proteins, and because
      these proteins are encoded by DNA organized into genes, molecular studies have
      shown that cancer is a paradigm of acquired genetic disease. The process of
      protein production involves a cascade of several different steps, each with its
      attendant enzymes, which are also encoded by DNA and regulated by other proteins.
      Most steps in the process can be affected, eventually leading to an alteration in
      the amount or structure of proteins, which in turn affects cellular function.
      However, whereas cellular function may be altered by disturbance of one gene,
      malignant transformation is thought to require two or more abnormalities
      occurring in the same cell. Although there are mechanisms responsible for DNA
      maintenance and repair, the basic structure of DNA and the order of the
      nucleotide bases can be mutated. These mutations can be inherited or can occur
      sporadically, and can be present in all cells or only in the tumor cells. At the
      nucleotide level, these mutations can be substitutions, additions or deletions.
      Several of the oncogenes discussed below, including the p53, c-fms, and Ras
      genes, can be activated by point mutations that lead to aminoacid substitution in
      critical portions of the protein. This article examines the current concepts
      relating to cellular mechanism that underlie the molecular alterations that
      characterize the development of cancer.

PMID- 16789601
TI  - [The Acapulco Declaration: a proposal to reduce incidence of diabetes in Mexico].
AB  - Type 2 diabetes is the main health problem in Mexico. The growing number of
      cases, the high percentage of individuals with chronic complications and the
      treatment's cost are among the explanations for the inability in the control of
      this disease. Diabetes prevention is most likely to reduce the rate of growth of
      this diabetes burden on our health system. At- risk individuals can be identified
      and several interventions have proved to be effective in decreasing diabetes
      incidence. Diabetes prevention related interventions can become a reality with
      the active participation of the government and society. Thus, a joint
      collaboration between the medical community, the government and society is needed
      to phase out the diabetes epidemic. Published diabetes prevention programs were
      reviewed and interventions feasible for Mexico were summarized in a document
      called "Declaracion de Acapulco". This paper was reviewed and approved by the
      Sociedad Mexicana de Nutricion y Endocrinologia; additional endorsement was
      obtained from several Mexican and international societies and institutions. The
      manuscript describes several initiatives, which can be applied in schools, work
      places, primary health services and by the government. Some of these are focused
      on the general population; others are applicable to at-risk individuals. The
      "Declaracion de Acapulco" is a-call-for-action position directed towards the
      whole society and designed to achieve effective diabetes prevention.

PMID- 16789602
TI  - Use of non-absorbable polypropylene mesh for the treatment of spontaneous renal
      graft rupture.
AB  - Renal graft rupture (RGR) is a life-threatening complication of kidney
      transplantation (KT), frequently associated with rejection and acute tubular
      necrosis. RGR repair with the use of suture, and corsetage with various materials
      (including synthetic glue, polyglactin absorbable hemostatic mesh, and
      lyophilized human dura), is indicated in non-severe cases. However, the
      employment of non-absorbable synthetic mesh had not been previously reported.
      Here, a case of a KT from cadaveric donor with RGR associated with acute
      rejection is reported. The graft was salvaged with the employment of a non
      absorbable polypropylene mesh. Six months after KT, the patient remains
      asymptomatic with normal renal function. To the best of our knowledge, this is
      the first report of the use of a non-absorbable polypropylene mesh to repair a
      RGR. In a setting in which economical restrictions are important, the use of non
      absorbable synthetic mesh may represent a good option of treatment.

PMID- 16789603
TI  - [Image of the month. Skin lesions revealing dermatomyositis].

PMID- 16789604
TI  - [Image of the month. An unusual case of acute aortic insufficiency].

PMID- 16789605
TI  - [How I treat...diaper dermatitis].
AB  - Diaper dermatitis is the most frequent skin disorder of the newborn. Several
      clinical types are distinguished. The most frequent type results from increased
      fragility of the newborn buttock skin when covered by diapers. According to the
      mechanisms involved and the severity of the dermatitis, one can distinguish the
      intertrigo of the chubby baby, and the so-called "W", "Y" and "red panties" types
      of diaper dermatitis. When the effects of occlusion are not controlled by
      adequate absorption by the diapers maceration of the stratum corneum occurs. As a
      result, degradation of the skin barrier function takes place. In addition, the
      value of the coefficient of friction of the skin increases with epidermal
      weakening to rubbing. In addition, fecal enzymes alter urines and skin. Judicious
      hygiene measures and a correct choice of care and diapers are mandatory.
      Cutaneous colonisation by microorganisms, in particular the yeasts Candida spp,
      is the main complication. Adequate preventive and curative measures can combat
      diaper dermatitis with confidence. A miconazole paste allows to improve the
      tribological properties of the interface between diapers and the skin. It also
      corrects the degradation of the skin barrier function, reduces inflammation and
      abates the impact of Candida spp. in the pathogenesis of the skin disorder.

PMID- 16789606
TI  - [Medication overuse headache].
AB  - Medication overuse headache (MOH) insidiously evolves from episodic migraine or
      tension-type headache because of overconsumption of analgesics, ergotamine or
      triptans. It affects 1-2% of the general population, but 15-20% of patients
      attending specialized headache centers. The precise neurobiologic mechanisms
      underlying this complication of episodic headaches are not well understood.
      Abnormalities of central monoaminergic systems have been suggested and substance
      dependence is more frequent in personal and family histories of affected
      subjects. In a recent FDG-PET study of 16 migraineurs with MOH before and after
      analgesics withdrawal we found a persistent hypometabolism of the medial
      orbitofrontal cortex, comparable to the one described after withdrawal in
      substance abuse. The orbitofrontal cortex plays a pivotal role in drive, decision
      making and drug dependence. We postulate that its hypoactivity predisposes
      certain migraineurs to MOH and to relapse after withdrawal. There is no unique
      management strategy for these patients, but medication withdrawal is a
      prerequisite for the effectiveness of preventive treatments and headache
      improvement.

PMID- 16789607
TI  - [Eotaxin: an important chemokine in asthma].
AB  - We know that the eosinophil plays an important role in asthma pathogenesis. This
      polynuclear cell is attracted into the airways by several chemokines. Eotaxin is
      one of them. Endothelial cells, smooth muscle cells, epithelial cells, alveolar
      macrophages and eosinophils can produce eotaxin. In asthmatic airways, eotaxin
      production is increased in bronchial airway lumen and mucosa. Eotaxine actively
      participates in asthma pathogenesis by activating eosinophil recruitment.

PMID- 16789608
TI  - [Physiopathology of respiratory muscles].
AB  - Different factors can have deleterious effect the inspiratory muscles: increased
      intrinsic mechanical loading of the inspiratory muscles, functional inspiratory
      muscle weakness, increased ventilatory demand related to capacity... These muscle
      changes influence exercise tolerance and contribute to dyspnea.

PMID- 16789609
TI  - [Quality of life, emollients and hydrating agents].
AB  - So-called dry skin is a quite common and annoying condition. This skin may affect
      individuals that are otherwise healthy. It may be particularly severe and
      unpleasant in cases of ichthyosis, atopic dermatitis or psoriasis. The inductive
      effects of the environment must not be ignored. Emollients and hydrating agents
      for the stratum corneum can help relieve the clinical manifestations.

PMID- 16789610
TI  - [Epilepsy in children with cerebral palsy].
AB  - The incidence of epilepsy in 110 patients with cerebral palsy (the majority with
      spastic tetraplegia) was 46,4%. Almost half of the patients with spastic
      tetraplegia (45%) and hemiplegia (52%) had epilepsy. The incidence was lower in
      patients with spastic diplegia (32%). Half of epilepsy in spastic hemiplegia were
      partial seizures and the other half consisted of generalized seizures, while
      generalized tonic-clonic episodes predominated in all other forms of C.P. A high
      incidence of West syndrome was observed in patients with spastic tetraplegia.
      Etiological factors of C.P. were perinatal in 75%. 16,65% had neonatal
      antecedents of convulsions; most of them had spastic tetraplegia (75%) and a
      significant mental retardation. A low intelligence quotient (I.Q.) was seen in
      most of the children with epilepsy, and patients with tetraplegia had
      significantly lower intelligence quotient than other groups.

PMID- 16789611
TI  - [Necrotizing fasciitis: diagnosis and treatments].
AB  - The necrotizing fasciitis is a medico-surgical emergency, characterized by the
      rapid speard of the infection in the subcutaneous tissue, involving fascia
      superficialis. Peaucity of cutaneous findings early in the course of the disease
      makes diagnosis a challenge for physician. Pain out of proportion to clinical
      findings, fever and signs of systemic toxicity are the keys in identification of
      necrotizing fasciitis. Delayed diagnosis lead to sepsis syndrom and/or multiple
      organ failure and correlate with poor oucome. Radiolographs, CT-scan or MRI are
      main radiologic studies, but such procedures should never delay surgical
      intervention. Intravenous antibiotics, fluid and electrolyte management and
      analgesia are needed in addition to radical debridment. Clindamycin, hyperbaric
      oxygen therapy and intravenous immunoglobulins are discussed treatments. Only
      prompt recognition and immediat care warrant a lower mortality and morbidity for
      this life-threatening infection.

PMID- 16789612
TI  - [Accommodating intraocular lenses].
AB  - Following cataract extraction, an implant is inserted into the capsular bag of
      the crystalline lens. Light rays are focused on the retina by the biconvex
      optical part of the implant. Most implants have monofocal and steady optic so
      that glasses are mandatory to get a corrected image according to the distance.
      Multifocal intraocular lenses have two drawbacks: a loss in visual acuity and
      perception of halos. Recently, we have optimised implants likely to offer a
      slight antero-posterior move of the optic. The efficiency of it is real, although
      limited. Those implants do not reduce visual acuity and do not create halos.

PMID- 16789613
TI  - [Bone densitometry for the diagnosis of osteoporosis: the Belgian reimbursement
      paradox].
AB  - Osteoporosis is considered as a major Public Health issue, in most developed
      countries. Bone mineral density assessment is the single best predictor of the
      future fracture risk for an individual. Belgium has the highest number of bone
      densitometers, per million habitants, in Europe. However, densitometry is not yet
      reimbursed in Belgium. This situation is rather paradoxical since the
      demonstration of a prevalent vertebral fracture or of a low bone mineral density
      is requested to obtain the reimbursement of drugs to be used for the management
      of osteoporosis. Hopefully, Belgium will soon be online with the requirement s of
      the European Commission, suggesting to make bone densitometry accessible, through
      reimbursement.

PMID- 16789614
TI  - [Pimecrolimus (Elidel) for a variety of skin diseases].
AB  - Pimecrolimus is an immune downregulator that belongs to the class of calcineurin
      inhibitors. Its efficacy is recognized for the topical treatment of the mild to
      moderate types of atopic dermatitis. In addition, the drug shows activity in a
      series of other dermatitides. We report a review of the international literature
      about this topic.

PMID- 16789615
TI  - [How I explore...outcomes in clinical trials: comments about recent studies of
      cardiovascular prevention].
AB  - The comparison of two therapeutic interventions requires the use of endpoints in
      randomized clinical trials, which supports evidence-based medicine. It is
      preferable to consider hard endpoints, such as major clinical events and
      mortality rather than biological or surrogate endpoints. In large cardiovascular
      prevention trials, it is now well accepted to analyze primary and secondary
      endpoints as well as to use combined clinical endpoints. Such composite endpoints
      offer the advantage of increasing the number of events, but have the disadvantage
      of diluting the therapeutic effect and of exposing to possible bias. We discuss
      this crucial issue at the light of controversial results from a few recent
      important cardiovascular prevention trials.

PMID- 16789616
TI  - [Clinical study of the month: ASTEROID: regression of coronary atherosclerosis
      with rosuvastatin at a maximal daily dose of 40 mg].
AB  - ASTEROID is a prospective, open-label blinded end-points trial aiming to assess
      whether very intensive statin therapy with rosuvastatin 40 mg/day could regress
      coronary atherosclerosis as determined by intravascular ultrasound (IVUS). This
      multinational study included 507 patients, among whom 349 had evaluable serial
      IVUS examinations at 24 months. Rosuvastatin decreased LDL cholesterol level from
      130 mg/dl to 61 mg/dl (- 53.2%) and increased HDL cholesterol from 43 to 49 mg/dl
      (+ 14.7%). The three prespecified IVUS efficacy parameters were positively
      altered by rosuvastatin, demonstrating regression of coronary atherosclerosis :
      the mean change in percent atheroma volume (- 0.98%), the change in atheroma
      volume in the most diseased 10-mm subsegment me (- 6.1 mm3) and the change in
      total atheroma volume (- 6.8%) were all significant (p < 0,001). Adverse events
      were infrequent and similar to other statin trials. The present study
      demonstrates that a 2-year treatment with a high dose of rosuvastatin 40 mg/day
      is able to induce significant regression of coronary atherosclerosis as
      determined by IVU imaging. Further ongoing studies in the GALAXY clinical
      investigation programme should now demonstrate that rosuvastatin, the most potent
      statin to reduce LDL and increase HDL cholesterol, is also able to diminish the
      incidence of clinical outcomes, cardiovascular events in general and major
      coronary events in particular.

PMID- 16789617
TI  - McCune-Albright syndrome: clinical picture and natural history in children and
      adolescents.
AB  - The classical triad of McCune-Albright syndrome (MAS) consists of polyostotic
      fibrous dysplasia (FD), skin hyperpigmentation (cafe-au-lait spots), and
      endocrine dysfunction, frequently seen in females as precocious puberty. Patients
      with MAS display mosaicism of activating somatic mutations of the alpha-subunit
      of Gs. Thus, the clinical presentation of each individual is dependent on the
      particular distribution of affected cells, causing a broad spectrum of endocrine
      and non-endocrine manifestations. Typical endocrinopathies are precocious
      puberty, hyperthyroidism, growth hormone excess, hyperprolactemia, and
      hypercortisolism. The onset of these manifestations is usually during infancy and
      childhood. Since specific treatment is required, the prognosis depends on the
      severity of each individual endocrine manifestation. Additionally, there are non
      endocrine manifestations, such as fibrous dysplasia of bone (FD), renal phosphate
      wasting, and skin hyperpigmentation, i.e. cafe-au-lait spots. FD, mostly
      polyostotic, causes fractures needing surgical and orthopedic treatment. Since
      previous studies have suggested the overall prognosis of patients with McCune
      Albright syndrome to be non-fatal, recent data have drawn our attention to non
      endocrine affections, including hepatobiliary dysfunction and cardiac disease,
      which are probably an important risk factor for early death. In summary, the
      clinical picture in MAS is related to its mosaic nature, i.e. any cell, tissue
      and organ in any site of the body could be affected to varying degrees, ranging
      from one or two mild clinical signs with excellent long-term prognosis to a
      severe life-threatening multiorgan disease.

PMID- 16789618
TI  - Image diagnosis in McCune-Albright syndrome.
AB  - McCune-Albright syndrome consists of polyostotic fibrous dysplasia, precocious
      puberty and cafe-au-lait skin lesions. Bone lesions are characterized by the
      presence of fibrous connective tissue with a characteristic whorled pattern and
      containing trabeculae of immature non-lamellar (woven) bone. They may be solitary
      (monostotic) or multiple (polyostotic). Commonly involved bones include the
      femur, tibia, ribs and facial skeleton. In the fibula pseudo-cystic areas and
      'ground glass'-like areas, in the femur 'shepherd crook' deformation due to
      weight on a less resistant bone and secondary to many cortical microfractures,
      are typical. MRI gives the exact delimitation of the lesions and is especially
      indicated in the followup of monostotic forms and in the outcome of surgical
      corrections. Bone scintigraphy with technetium 99 is essential in the follow-up
      of the disease. Ultrasonography is very useful in ovarian cyst follow-up and in
      the detection of thyroid and adrenal nodules and testicular microlithiasis.

PMID- 16789619
TI  - Laparoscopic management of ovarian cysts in peripheral precocious puberty of
      McCune-Albright syndrome.
AB  - Ovarian cysts are common in peripheral precocious puberty in McCune-Albright
      syndrome (MAS). The clinical course of these cysts is unpredictable due to
      episodes of hyperestrogenism typical of MAS ovarian hyperfunction. In persistent
      and recurrent large ovarian cysts with sustained estrogen hypersecretion and
      relevant clinical disturbances (increased linear growth and bone age maturation,
      vaginal bleeding and psychological disturbances) treatment is mandatory.
      Experimental courses of estrogen-blocking drugs may have insufficient or nil
      therapeutic effects. In these cases and when molecular analysis is required to
      obtain MAS diagnosis as in isolated peripheral precocious puberty, surgery is the
      option. Laparoscopy minimizes surgical aggression and facilitates obtaining
      tissue samples for molecular analysis, and sometimes relieves hyperestrogenism
      with the excision of hyperactive ovarian areas. It can be conducted with trans
      umbilical laparoscopic ovarian cystectomy (TULOC) before 3 years of age and with
      traditional techniques afterwards.

PMID- 16789620
TI  - Genetics of McCune-Albright syndrome.
AB  - McCune-Albright syndrome (MAS) is a rare proteiform disease due to postzygotic,
      somatic mutations at codon R201 of the GNAS1 gene that results in cellular
      mosaicism. Different methods have been used in the molecular analysis of DNA
      samples from several tissues of patients with one or more MAS signs, with various
      mutation detection rates. We review data from the literature to investigate
      whether patient inclusion criteria for GNAS1 analysis, the molecular methods used
      to search for R201 mutations, and the type of tissues analysed, can influence the
      mutation detection rate in MAS. Our study indicates that to overcome the problems
      related to GNAS1 analysis in MAS, sensitive and specific molecular methods must
      be used to look for the mutation from all available affected tissues and from
      easily accessible tissues, and even more so in the presence of atypical and
      monosymptomatic forms of MAS.

PMID- 16789621
TI  - Bisphosphonate treatment of bone fibrous dysplasia in McCune-Albright syndrome.
AB  - One of the main features of McCune-Albright syndrome is bone fibrous dysplasia
      (BFD) often associated with severe clinical outcomes, such as bone pain, bone
      deformities and pathological fractures. Medical treatment with bisphosphonates
      started 15 years ago. Recent trials in pediatric patients with BFD have shown
      encouraging results. We evaluated long-term efficacy and safety of pamidronate
      treatment of BFD in children and adolescents with MAS. The drug was administered
      at 4 month-1 year intervals according to alkaline phosphatase levels. The study
      included 14 patients (10 females and 4 males between the ages of 5.3 and 18.7
      years) with moderate or severe BFD. Follow up lasted 1.9-9 years. Bone pain,
      fractures, deformities, and bone turnover markers were evaluated before every
      therapeutic course. The study shows the beneficial effects of long-term
      bisphosponate treatment on BFD lesions leading to reduced fracture rate and bone
      pain, and radiological evidence of long bone lesion healing.

PMID- 16789622
TI  - Craniofacial surgery in fibrous dysplasia.
AB  - Cranio-orbital fibrous dysplasia usually causes proptosis, visual loss, ocular
      motility impairment and cosmetic deformity. The goals of cranial fibrous
      dysplasia management are to preserve neurological functions and improve cosmesis.
      Strict neurological and ophthalmological follow-up and early cranio-facial
      surgery enables non-aggressive treatment without significant morbidity.
      Furthermore, good results are achieved thanks to new techniques and materials
      especially in children and adolescents. The aim of the present paper is to
      discuss surgical indications, techniques and outcomes of cranio-facial-orbital
      fibrous dysplasia on the basis of personal experience of 14 patients who
      underwent surgery.

PMID- 16789623
TI  - Gs alpha-related precocious puberty in females: focus on treatment.

PMID- 16789624
TI  - McCune-Albright syndrome: persistence of autonomous ovarian hyperfunction during
      adolescence and early adult age.
AB  - Gonadal hyperfunction is the most frequent endocrine dysfunction in females with
      McCune-Albright syndrome (MAS). Peripheral precocious puberty is usually the
      first MAS manifestation in children, characterized by episodes of hypersecretion
      of estrogens with a consequent reduction in gonadotropin secretion. Little is
      known about the course of this endocrine disease in adolescence and during young
      adult life. The aim of this study was to evaluate ovarian function in 10 females
      with MAS (age 11.4-20.1 years) to detect the persistence of autonomous ovarian
      hyperfunction throughout and following adolescence, after at least 1 year wash
      out of any treatment for precocious puberty. LH, FSH, estradiol, prolactin,
      androgen secretion, ovarian and breast sonography in luteal and follicular phases
      of some menstrual cycles were evaluated. We demonstrated the persistence of some
      ovarian autonomy, documented by hyperestrogenism and/or low or absent
      gonadotropin secretion and/or ovarian cysts.

PMID- 16789625
TI  - Clinical presentation of McCune-Albright syndrome in males.
AB  - The aims of this study were: (a) to survey gender prevalence and clinical
      findings at diagnosis in a series of patients who manifested at the time of this
      study the classical triad of McCune-Albright syndrome (MAS); (b) to investigate
      whether clinical presentation of MAS in boys may be different from that in girls;
      (c) to confirm whether boys with MAS may show a peculiar picture of testicular
      microlithiasis (TM) by testicular ultrasonography (US). Twenty-six patients (10
      boys) with the classical clinical manifestations of MAS were recruited for the
      present study from the database of the Italian Multicenter Study Group on MAS.
      Age at diagnosis of MAS was significantly lower in girls than in boys (p <
      0.025). Whilst there was no difference in the prevalence of skin and bone fibrous
      dysplasia for the two groups, a significantly higher prevalence of peripheral
      precocious puberty (PPP) was found in girls (chi2 = 6.5, p < 0.025). Moreover,
      PPP onset was earlier in females than in males (2.8 +/- 2.3 vs. 6.9 +/- 2.7
      years, p < 0.005). In one boy, aged 2.9 years, the first clinical manifestation
      of MAS was monolateral testicular enlargement in the context of a picture of
      classical PPP. US scanning of the testes, at the time of the present study,
      showed bilateral hyperechogeneic multiple spots, compatible with diagnosis of TM,
      in 6/10 boys. CONCLUSIONS: (a) MAS is slightly more frequent in females. (b) PPP
      in MAS is significantly more frequent and earlier in girls. (c) PPP in boys with
      MAS is generally associated with bilateral testicular enlargement, but
      monolateral macroorchidism may also be seen. (d) TM may be another marker for MAS
      in males.

PMID- 16789626
TI  - McCune-Albright syndrome: growth hormone and prolactin hypersecretion.
AB  - McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its
      pathogenesis results in hypersecretion of hormones in peripheral endocrine
      tissues. This can be expressed as precocious puberty, mainly in girls, primary
      hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism
      and hypercortisolism. The incidence of GH excess among patients with MAS has been
      assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not
      completely understood, whereas it seems to be different from the aetiology of
      acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess
      can be masked because of precocious puberty or craniofacial fibrous dysplasia,
      indicating the necessity for screening. Medical treatment is usually the only
      option in MAS patients with GH excess, as transsphenoidal surgery is usually
      restricted due to massive thickening of the skull base, whereas radiotherapy is
      contraindicated due to probable higher predisposition to sarcomatous
      transformation. The use of bromocriptine, cabergoline and octreotide, or the
      combination of these, has shown variable results, whereas pegvisomant, a GH
      receptor antagonist, is a new promising option, although not yet used in patients
      with MAS.

PMID- 16789627
TI  - Pseudohypoparathyroidism: history of the disease.

PMID- 16789628
TI  - Genetics of pseudohypoparathyroidism types Ia and Ic.
AB  - Pseudohypoparathyroidism (PHP) types Ia and Ic result from heterozygous
      inactivating mutations of Gs alpha, the alpha-subunit of the heterotrimeric
      stimulatory G-protein, Gs. Both are characterized by a combination of Albright's
      hereditary osteodystrophy and, when the mutation is maternally inherited, end
      organ resistance to multiple hormones. Due to complex tissue-specific imprinting
      of Gs alpha, paternally-derived mutations do not usually lead to hormone
      resistance. More than 100 mutations have been characterized in patients with PHP
      Ia and one mutation in type Ic. These are scattered throughout the gene, with one
      significant mutational hotspot in exon 7. Identification of mutations in a
      clinical service setting is important for accurate genetic counselling and
      clinical management of affected families. However, only 70-80% of mutations are
      identified by direct sequencing of coding exons and splice junctions. Screening
      for whole exon deletions and intronic or regulatory mutations in mutation
      negative families is therefore now an important priority to establish the full
      mutational spectrum in these conditions.

PMID- 16789629
TI  - Different mutations within or upstream of the GNAS locus cause distinct forms of
      pseudohypoparathyroidism.
AB  - The term pseudohypoparathyroidism (PHP) refers to different disorders that are
      caused by mutations within GNAS or upstream of this complex genetic locus. GNAS
      gives rise to several different transcripts, including Gs alpha (alpha-subunit of
      the heterotrimeric stimulatory G protein), XL alpha s (extra-large variant of Gs
      alpha), and several additional sense and antisense transcripts. The complexity of
      the GNAS locus is furthermore reflected by a parent-specific methylation pattern
      of most of its different promoters. PHP can be divided into two major groups, PHP
      type Ia (PHP-Ia) and PHP type Ib (PHP-Ib). PHP-Ia is caused by heterozygous
      mutations affecting one of the 13 GNAS exons encoding Gs alpha. In contrast, PHP
      Ib is caused by heterozygous deletions within STX16, the gene encoding syntaxin
      16, which is located more than 220 kb upstream of GNAS, or by deletions within
      GNAS involving exon NESP55 and two of the antisense exons. In either form of PHP,
      hormonal resistance develops only after maternal inheritance of the mutation,
      while paternal inheritance of the same molecular defect is not associated with
      endocrine abnormalities. In most familial cases of PHP-Ib, there is a loss of
      exon A/B methylation combined with active A/B transcription from both parental
      alleles, which leads to suppression of Gs alpha transcription in the proximal
      renal tubules and, therefore, PTH resistance.

PMID- 16789630
TI  - Determination of Gs alpha protein activity in Albright's hereditary
      osteodystrophy.
AB  - Albright's hereditary osteodystrophy (AHO) is a heterogeneous clinical entity in
      part associated with pseudohypoparathyroidism (PHP) and other endocrinopathies.
      It may be caused by diminished Gs alpha protein activity. Heterozygous mutations
      in the underlying GNAS gene on chromosome 20 have been described. One hundred and
      six patients with suspected AHO, were investigated, of whom 93 showed a
      laboratory profile of PHP with low or normal calcium and elevated parathormone
      with normal vitamin D metabolites, and 13 had no endocrine abnormalities. Gs
      alpha activity was determined in isolated erythrocyte membranes. Molecular
      genetic analysis of GNAS exons 2-13 was initiated. Significantly reduced Gs alpha
      activity was found in 91 patients. In 53 patients with reduced Gs alpha activity,
      a mutation within GNAS was demonstrated. The mutation detection rate was much
      lower in AHO patients without endocrinopathies than in those who had PHP. In
      addition, three of the 15 patients with AHO features but normal Gs alpha activity
      had genetic variations of GNAS. We conclude that determination of Gs alpha
      activity can be used as a diagnostic screening procedure in patients with
      suspected AHO. However, the mutation detection rate in GNAS is highly variable.
      The genetic heterogeneity of AHO needs further investigation.

PMID- 16789631
TI  - Multihormonal resistance to parathyroid hormone, thyroid stimulating hormone, and
      other hormonal and neurosensory stimuli in patients with
      pseudohypoparathyroidism.
AB  - In patients with pseudohypoparathyroidism, hormonal resistance first affects
      parathyroid hormone (PTH), which leads to calcipenia, a decrease in renal vitamin
      D activation, and a tendency to bone receptor remodeling. However, because G
      proteins are ubiquitously distributed, multiple hormonal resistance occurs in
      pseudohypoparathyroidism type Ia and type Ic, impairing responses to other
      calciotropic hormones (PTHrP, calcitonin), TSH, and also pituitary and
      hypothalamic hormones, and to neurosensory stimuli. The diversity of
      multihormonal resistance contributes to the various phenotypes of the disease.
      Some clinical discomfort and medical consequences of the disease can be treated
      or prevented with hormone supplementation or modulation.

PMID- 16789632
TI  - Resistance to growth hormone releasing hormone and gonadotropins in Albright's
      hereditary osteodystrophy.
AB  - Heterozygous inactivating mutations in the Gs alpha gene cause Albright's
      hereditary osteo-dystrophy (AHO). Consistent with the observation that only
      maternally inherited mutations lead to resistance to hormone action
      (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence
      for a predominant maternal origin of Gs alpha transcripts in endocrine organs,
      such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display
      variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating
      hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH).
      Although the incidence and the clinical and biochemical characteristics of PTH
      and TSH resistance have been widely investigated and described, the cause and
      significance of the reproductive dysfunction in AHO is still poorly understood.
      The clinical finding of alterations of GH secretion in these patients was
      described for the first time only 2 years ago. The present report briefly reviews
      the literature focusing on the actual knowledge about these last two subjects.

PMID- 16789633
TI  - Albright's hereditary osteodystrophy.

PMID- 16789634
TI  - Fertility in patients with congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is generally regarded as a paediatric
      endocrine disease, but nowadays nearly all patients reach adulthood as a result
      of improved diagnosis and treatment. It is now increasingly recognised that
      treatment goals shift during life: one of the major treatment goals in childhood
      and puberty, i.e. normal growth and development, is no longer relevant after
      childhood, whereas other aspects, such as fertility and side effects of long-term
      glucocorticoid treatment, become more important in adulthood. This paper focuses
      on fertility in male and female adult patients with CAH. In males with CAH the
      fertility rate is reduced compared with the normal population, the most frequent
      cause being testicular adrenal rest tumours. Development and growth of these
      tumours is assumed to be ACTH dependent and undertreatment may play an important
      role. If intensifying glucocorticoid treatment does not lead to tumour decrease,
      surgical intervention may be considered, but the effect on fertility is not yet
      known. In females with CAH the degree of fertility depends on the phenotype of
      the CAH. Most fertility problems are seen in the classic salt-wasting type. Age
      of menarche and regularity of the menstrual cycle depends on the degree of
      adrenal suppression. Not only adrenal androgens have to be normalised but also
      the levels of adrenal progestins (progesterone and 17-OH-progesterone) that
      interfere with normal ovulatory cycles. The regularity of menstrual cycles can be
      considered as an important measure of therapeutic control in adolescent females
      with CAH and therefore as a therapeutic goal from (peri)pubertal years on. Other
      factors that contribute to impaired fertility in females with CAH are ovarian
      hyperandrogenism (polycystic ovary syndrome), ovarian adrenal rest tumours,
      genital surgery and psychological factors. Subfertility in CAH can have its
      origin already in the peripubertal years and is therefore of interest to the
      paediatric endocrinologist.

PMID- 16789635
TI  - Pituitary dysfunction following head injury--a common problem, rarely diagnosed.

PMID- 16789636
TI  - Hypothalamo-hypophysial dysfunction after traumatic brain injury in children and
      adolescents: a preliminary retrospective and prospective study.
AB  - With two study protocols, one retrospective and the other prospective, we
      evaluated hypothalamo-hypophysial dysfunction (HHD) in paediatric patients
      treated for traumatic brain injury (TBI) in the neurosurgical or intensive care
      department at our hospital. The retrospective group comprised 22 patients who had
      experienced TBI 0.7-7.25 years before the study. The prospective group included
      30 patients assessed at TBI (T0), 26 of 30 after 6 months (T6), and 20 of 26
      after 12 months (T12). Auxological and hormonal basal parameters of hypothalamo
      hypophysial function were evaluated at recall in the retrospective group, and at
      T0, T6 and T12 in the prospective group. Basal data and standard dynamic tests in
      selected patients revealed one with precocious puberty, one with total anterior
      hypopituitarism, one with central hypogonadism, and one with growth hormone (GH)
      deficiency in the retrospective group; three patients with cerebral salt-wasting
      syndrome, one with diabetes insipidus and seven with low T3 syndrome at T0 (all
      transient), one with hypocorticism at T6 confirmed at T12, and one with GH
      deficiency at T12 in the prospective group. The results of our study show that
      post-TBI HHD in our paediatric cohort is not uncommon. Of the 48 patients who
      underwent a complete evaluation (22 retrospective study patients and 26
      prospective study patients evaluated at T6) five (10.4%) developed HHD 6 months
      or more after TBI. HHD was newly diagnosed in one previously normal patient from
      the prospective group at 12 months after TBI. GH deficiency was the most frequent
      disorder in our paediatric cohort.

PMID- 16789637
TI  - Blood pressure in patients with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency.
AB  - BACKGROUND: In patients with congenital adrenal hyperplasia (CAH) recording of
      blood pressure (BP) must be included in monitoring treatment to detect
      hypertension. AIM: To investigate the BP patterns in patients with CAH. METHODS:
      Twenty-three children and adolescents (age 6-17 years) and 11 adult patients (age
      18-26 years) were studied (21 females, 13 males; 28 salt-wasting patients). In
      the whole group BP in the outpatient clinic was compared with BP under
      hospitalisation and in 11 of the children and adolescents also with 24-hour
      ambulatory blood pressure monitoring (ABPM). RESULTS: BP in the ward in children
      and adolescents but not in adults was significantly higher than BP in the
      outpatient clinic, where BP was in the upper normal range. There was also a
      significant difference between BP in the outpatient clinic and the lower ABPM in
      the 11 patients tested. Atrial natriuretic peptide (ANP) in blood serum showed
      normal values. CONCLUSIONS: BP measured in outpatients in a relaxed and calm
      atmosphere meets the requirements for monitoring of treatment. Measurement of BP
      on the ward leads to falsely high results. ABPM is not necessary. Estimation of
      ANP provides no additional information.

PMID- 16789638
TI  - Asymptomatic cardiomyopathy in children and adolescents with type 1 diabetes
      mellitus: association of echocardiographic indicators with duration of diabetes
      mellitus and metabolic parameters.
AB  - This study was designed to determine the relationship of dimensions, wall
      thickness and function of the left ventricle with diabetes duration, fasting
      blood glucose, lipid profile, beta-OH-butyrate, free fatty acids (FFA) and
      carnitine levels in children and adolescents with type 1 diabetes mellitus (DM1)
      who had no cardiovascular complications. Thirty-five patients with DM1 (18 F/17
      M, mean age: 12.0 years) and age matched control children (n = 24) were enrolled
      in the study. Patients with DM1 were subdivided into Group I (mean DM1 duration
      3.5 years, n = 14), and Group II (mean DM1 duration 8.2 years, n = 21).
      Dimensions, wall thickness and systolic functions of the left ventricle were
      normal in all patients with DM1. Diastolic functions were normal in Group I. In
      Group II, peak A wave velocity (AVEL) (p = 0.004), velocity-time integral of A
      wave (AVTI) (p = 0.007) and isovolumetric relaxation time corrected by heart rate
      (cIVRT) (p = 0.048) were high, and peak E wave velocity (EVEL) and velocity-time
      integral of E wave (EVTI) were normal. E/A (p < 0.0001) and EVTI/AVTI (p = 0.001)
      were low in this group. In Group I, systolic and diastolic blood pressure, HDL
      cholesterol and FFA values were normal; total cholesterol (p = 0.047), LDL
      cholesterol (p = 0.017), beta-OH-butyrate (p = 0.003), and acetyl carnitine (p =
      0.006) levels were high. In Group II, diastolic blood pressure (p = 0.008), total
      cholesterol (p < 0.0001) and LDL-cholesterol (p < 0.0001) were increased; and
      total carnitine (p = 0.019), free carnitine (p = 0.002) and HDL-cholesterol (p =
      0.039) were decreased. Correlations were detected between total carnitine and
      AVEL and HR; free carnitine and AVEL, E/A and HR; HbA1c and EVTI/AVTI and cIVRT;
      LDL-cholesterol and E/A, EVTI/AVTI ratios and cIVRT; HDL-cholesterol and AVEL;
      FFA and LVDD, IVSD, LVPWD, LVmass and CO; metabolic parameters and DM1 duration
      and echocardiographic findings such as AVEL, EVEL, EVTI, VmaxAV and CO. In
      conclusion, left ventricular dimensions, wall thickness and systolic functions
      were normal in children and adolescents with DM1 who had no obvious
      cardiovascular complications. Left ventricular diastolic functions were abnormal
      in patients of Group II. Left ventricular diastolic function abnormalities were
      associated with glycemic control, free and total carnitine, and LDL- and HDL
      cholesterol levels.

PMID- 16789639
TI  - The relationship of maternal iodine status and neonatal thyrotropin
      concentration: a study in Southern Thailand.
AB  - Iodine deficiency disorder (IDD) is a global health problem. Previous studies in
      Southern Thailand have shown that the prevalence of goiter in schoolchildren is 3
      5%, indicating that Southern Thailand is an iodine sufficient area. We conducted
      a study in pregnant women to determine their iodine status and whether there was
      an association between maternal urinary iodine excretion (UIE) and the neonatal
      thyrotropin (TSH) concentration. We recruited 244 pregnant women attending the
      antenatal clinic at Songklanagarind Hospital. Their mean age was 28.5 +/- 5.3
      years (range 15-42) with a mean gestation age of 9.4 +/- 2.7 weeks (range 6-15).
      Ten ml urine was collected for UIE measurement. All women were delivered at
      Songklanagarind Hospital. The mean gestational age at delivery was 38.2 +/- 2.1
      weeks (range 28-41). The median maternal UIE was 139.5 microg/l with 78 (32%)
      women having UIE below 100 microg/l. The median TSH of the infants was 4.14 mIU/l
      (range 0.30-17.89) with 88 (36.1%) of infants having TSH concentration above 5
      mIU/l. Logistic regression analysis revealed that the odds ratio of pregnant
      women with UIE below 100 microg/l giving birth to infants with neonatal TSH above
      5 mIU/l was 2.04 (95% confidence interval 1.17-3.66, p = 0.012). In conclusion,
      our findings demonstrate that 32% of pregnant women have UIE below 100 microg/l,
      and that UIE below 100 microg/l in pregnant women is associated with neonatal TSH
      concentration above 5 mIU/l. These findings suggest that iodine deficiency is
      prevalent in pregnant women in Southern Thailand.

PMID- 16789640
TI  - Genetic variants in the promoter region of the IGF-I gene as a reason for short
      stature.
AB  - DNA obtained from the blood cells of 88 adolescent patients with short stature,
      with low blood serum IGF-I concentrations, normal growth hormone (GH) secretion
      and normal GH receptor (GHR) structure, was analyzed in the promoter region for
      the IGF-I gene. A total of 24 genetic variants was detected in the DNA of 13
      patients. An attempt was also made to analyze the impact of identified mutations
      on DNA-protein interactions using EMSA.

PMID- 16789641
TI  - Plasminogen activator inhibitor-1 (PAI-1) gene polymorphism (-675 4G/5G)
      associated with obesity and vascular risk in children.
AB  - Atherothrombotic complications in insulin resistance are partly attributed to
      impaired fibrinolysis caused by increased PAI-1 plasma levels, and 4G/5G promotor
      polymorphism of the PAI-1 gene may modulate PAI-1 transcription. OBJECTIVE: To
      investigate PAI-1-675 4G/5G allele gene polymorphism and its relationship with
      obesity in children. CHILDREN AND METHOD: The study participants were 133
      apparently healthy non-obese children, 24 probable exogenously obese without
      family history (Group I), 66 probable familial obese (Group II), and 44 obese
      children who were referred to the pediatric endocrinology department with any
      complication of obesity (Group III). Group I and Group II obese children were
      gathered from a school-based epidemiological study. RESULTS: Incidence of obesity
      was 19% in a school with high socio-economic status, whereas it was 4% in a
      school with low socio-economic status. Frequencies of 4G/4G gene polymorphisms
      were 24.81%, 37.50%, 64.80% and 61.11% in the control group, and groups I, II,
      and III, respectively. In groups II and III, 4G/4G gene polymorphism, and in non
      obese control children 5G/5G gene polymorphism, was common. In obese children in
      the presence of family history for obesity and metabolic syndrome (odds ratio
      [OR]: 4.48, 95% confidence interval [CI]: 1.26-15.82), carriage of the 4G allele
      either in heterozygous or homozygous state increased the risk of vascular disease
      (OR: 6.10, 95% CI 1.64-22.90). In patients with acanthosis nigricans, high HOMA
      IR values, hypertriglyceridemia and elevated atherogenic index, 4G/4G genotype
      frequency was remarkably higher compared to patients with other features of
      metabolic syndrome. CONCLUSION: The increasing prevalence of childhood obesity in
      high socio-economic status is associated with health risks. In obese children
      with family history of obesity and cardiovascular disease or type 2 diabetes
      mellitus and in obese children who had any feature of metabolic syndrome,
      frequency of 4G/4G genotype was more than the 4G/5G and 5G/5G genotypes in the
      PAI-1 gene. These patients can be at increased risk for developing vascular
      disease. Acanthosis nigricans, high HOMA-IR value, hypertriglyceridemia and high
      atherogenic index can also reflect the high risk of vascular disease in metabolic
      syndrome.

PMID- 16789642
TI  - Childhood sporadic pheochromocytoma: clinical profile and outcome in 19 patients.
AB  - Sporadic pheochromocytoma is a rare tumor of childhood and accounts for less than
      1% of cases of hypertension. We describe the presentation and outcome of 19
      adolescents with sporadic pheochromocytoma seen over past 10 years at a tertiary
      care center in north India. The mean age (+/- SD) at presentation was 15.1 +/-
      2.4 years with range from 9-18 years. The male to female ratio was 12:7. The lag
      time between onset of symptoms to diagnosis ranged from 1 month to 5 years with
      mean (+/- SD) of 1.09 +/- 1.02 years. The majority of children presented with
      hypertension and paroxysms. Paroxysms, characterized by the triad of headache,
      palpitations and sweating, was present in 13 (68%) of these patients. Twelve
      (63%) patients had postural fall in blood pressure, ten (53%) had abdominal pain,
      four (21%) had visual blurring, and three (16%) each had palpable abdominal mass
      and significant weight loss at presentation. Nausea and vomiting are common
      symptoms in children with pheochromocytoma and were present in six (32%) and
      three (16%) patients, respectively. Cafe-au-lait macule was present in only two
      (11%) patients. Urinary vanilyl mandelic acid (VMA) was found to be significantly
      high in ten (53%) patients, and urinary epinephrine and norepinephrine in eight
      (42%). Six (32%) patients had both VMA and urinary epinephrine and norepinephrine
      within normal limits and five (26%) had significant elevation of both. The tumor
      was localized by ultrasonography in 17 (89%) patients and by computed tomography
      in 18 (95%), and in one patient it was localized by 131I-MIBG scan. Sixteen (84%)
      patients had adrenal pheochromocytoma (including four with bilateral masses),
      while the remaining three (16%) had abdominal extra-adrenal pheochromocytoma
      originating from sympathetic ganglions. The mean (+/- SD) diameter of the tumor
      was 4.4 +/- 1.7 cm, ranging from 2.2-7.5 cm. Pre-operatively, hypertension was
      managed by phenoxybenzamine in six (32%), sustained release prazosin in 12 (63%),
      beta-blockers in 14 (74%), calcium channel blockers in 12 (63%), and angiotensin
      converting enzyme inhibitors and diuretics in only two (11%) patients. Eighteen
      (85%) patients underwent exploratory laparotomy for removal of the tumor. On
      follow-up, 13 (72%) patients became normotensive, while six (32%) patients
      continued to have hypertension. In conclusion, childhood pheochromocytoma is
      characterized by atypical symptomatology; ultrasonography is a useful modality in
      localizing the lesions in the majority of patients; surgery is rewarding in most
      patients.

PMID- 16789643
TI  - Malignant insulinoma in childhood.
AB  - Pancreatic tumors constitute a rare surgical problem in infancy and childhood.
      Insulinomas are rare in all age groups with an estimated incidence of one per
      250,000 person-years and even rarer in childhood. We report a 10 year-old girl
      with malignant insulinoma. The presenting symptom was hypoglycemic attacks.
      Laboratory investigation demonstrated that the hypoglycemia was due to
      hyperinsulinism. MRI of the abdomen revealed a mass at the tail of the pancreas.
      Distal pancreatectomy with splenectomy was performed. Histological examination
      showed malignant insulinoma with peripancreatic lymph node metastases. One month
      later abdominal MRI revealed the existence of multiple small metastatic foci in
      the liver, which were confirmed by In111 octreoscan. Treatment with octreotide
      was started and the disease is stable after 12 months of therapy.

PMID- 16789644
TI  - An unusual case of chromosome 22q11 deletion syndrome with psychiatric disorder,
      hypoparathyroidism and precocious puberty.
AB  - Deletions of chromosome 22q11 cause a wide range of phenotypes; even affected
      members from the same family may present with different phenotype. We present an
      11-3/12 year-old boy who has 22q11 deletion in a hitherto unreported combination
      with psychiatric disorder, hypoparathyroidism and precocious puberty. Whether
      precocious puberty is a clue for chromosome 22q11 deletion syndrome is also
      discussed.

PMID- 16789645
TI  - Triple-A syndrome--the first Chinese patient with novel mutations in the AAAS
      gene.
AB  - We report on the first Chinese patient with triple-A syndrome, who presented at
      22 months with status epilepticus secondary to hyponatraemia and hypoglycaemia.
      Subsequent endocrine investigations confirmed primary adrenal insufficiency and
      aldosterone deficiency. In the presence of achalasia and alacrima, this patient
      satisfies the diagnostic criteria of triple-A syndrome. Further molecular testing
      detected compound heterozygous mutations in the AAAS gene: a c.580C --> T
      transition in exon 7 and a c.771delG single nucleotide deletion in exon 8.
      Testing of parents and brother confirmed their heterozygous carrier status.

PMID- 16789646
TI  - Menstruation in a 2 month-old infant with salt-losing congenital adrenal
      hyperplasia (CAH).

PMID- 16789648
TI  - Are college students more disturbed today? Stability in the acuity and
      qualitative character of psychopathology of college counseling center clients:
      1992-1993 through 2001-2002.
AB  - Are clients at college counseling centers more disturbed today than they were 5,
      10, or 20 years ago? Since the mid-1980s, counseling center personnel have
      consistently perceived student clients as more distressed or reported acutely
      distressed clients as more prevalent than they did 1, 3, or 5 years ago. Only 3
      studies employing a systematic, data-based methodology have addressed this
      question. Two researchers used different actuarial measures of the acuity or
      character of client pathology and concluded that current student clients are not
      more disturbed than were earlier ones. One researcher used clinical judgments
      rendered at the end of therapy and concluded that current students were more
      distressed. Using the Personality Assessment Inventory, the author found the
      actuarially determined quantitative and qualitative indices of pathology
      unchanged for 3,400 counseling center clients seen during 10 consecutive years.
      Over the same period, the use of medications increased fivefold. An actuarial
      measure of client distress appears crucial to both accurate diagnosis and
      treatment and to the adequate preparation of future counseling center
      professionals.

PMID- 16789647
TI  - College psychiatry as public health psychiatry. 1967.
AB  - This ten-year survey of the use of student mental health services offered by the
      University of North Carolina suggests that increased usage over time has been due
      to greater availability of staff and a broadening of services offered rather than
      to an increase of the prevalence of mental illness among the student body. The
      authors believe that college psychiatry, as one of the earliest examples of the
      provision of mental health services to a community, can be used as a model for
      other aspects of public health psychiatry.

PMID- 16789649
TI  - College psychiatry 2006: challenges and opportunities.

PMID- 16789650
TI  - College student suicide in the United States: 1990-1991 through 2003-2004.
AB  - Suggestions that there is a growing epidemic of suicide among college students in
      the United States are false. The National Survey of Counseling Center Directors
      reports 1,404 student suicides over a 14-year period and an adjusted suicide rate
      of 6.5, half the rate of the general US population (12.6 for all races) during
      this period when matched for gender and age. Counseling centers appear effective
      in treating suicidal students, for although the suicide rate for students who
      were currently or previously clients at campus counseling centers is 3 times the
      rate of other students, student clients have 18 times the risk of suicide
      compared to students in general. Identifying and referring students at elevated
      risk for suicide could further reduce the crude and relative rate of student
      suicide. However, even programs that do this only moderately well may require
      substantial increases in counseling staffing.

PMID- 16789651
TI  - Four eras of study of college student suicide in the United States: 1920-2004.
AB  - Studies of college student suicide can be grouped into the following 4 eras: 1920
      1960, 1960-1980, 1980-1990, and 1990-2004. The suicide rate for students has
      declined monotonically across these 4 eras, from 13.4 to 8.0 to 7.5 and, most
      recently, to 6.5. The decreasing proportion of men in the student populations
      studied largely accounts for this decline. Since 1960, the suicide rate for
      students has consistently been about half the rate of the general US population,
      matched for age and gender. This highly favorable relative suicide rate is the
      result of firearms having been effectively banned from campuses. Additional
      population-oriented approaches warrant implementation to further reduce student
      suicide rates. Approaches focused on high-risk groups also hold promise. These
      findings are based upon and may be most valid for the 70% of all students who
      attend 4-year colleges and universities full time.

PMID- 16789652
TI  - Should colleges withdraw students who threaten or attempt suicide?

PMID- 16789653
TI  - Epidemiologic aspects of college mental health. 1971.

PMID- 16789654
TI  - Student assistance program: a new approach for student success in addressing
      behavioral health and life events.
AB  - College health centers, whether large or small, often find it challenging to
      provide counseling and supportive services for all students (including remotely
      located students) 24 hours a day, 7 days a week. Student assistance programs
      (SAPs) are services provided to students through a contractual arrangement to the
      university or college as a part of student services. The goal is to address
      psychosocial concerns that may interfere with academic performance within the
      realm of short-term counseling. These services range from traditional behavioral
      health concerns about stress and depressive reactions to how to find child care
      with foreign-speaking services. In this article, the authors describe a method to
      provide such short-term counseling to a 2,200-student health-science campus. They
      present data from 1 year of service as well as the benefits and limitations.

PMID- 16789655
TI  - Aftermath of tragic events: the development and use of community support meetings
      on a university campus.
AB  - Colleges and universities need to be prepared to address the psychological impact
      of tragedies on their campuses. In this article, the author describes the
      development and successful implementation of campus postvention services in the
      aftermath of college student deaths by suicide as well as by natural and
      accidental causes. The program has been well received and has gone a long way
      toward helping the campus community come together and heal after these types of
      tragedies. College officials adapted the program to address issues related to
      troubling national and international events as well local incidents, such as
      suicide attempts and students' loss of housing through fires. The author provides
      specific instructions so that readers can replicate the program on their own
      campuses, and additional materials are available upon request.

PMID- 16789656
TI  - The way it's supposed to be.

PMID- 16789657
TI  - Sloppy calls.

PMID- 16789659
TI  - What's-up docs.

PMID- 16789658
TI  - Driver down!

PMID- 16789660
TI  - Docs on demand.

PMID- 16789661
TI  - Birds of a feather flock together.

PMID- 16789662
TI  - Taking EMS into tomorrow: part 2.

PMID- 16789663
TI  - Beyond the basics: scene safety.

PMID- 16789664
TI  - Improving ambulance safety.

PMID- 16789665
TI  - In Winter Park, employee safety comes first.

PMID- 16789666
TI  - Safe intersection practices.

PMID- 16789667
TI  - How to write a job description that's accurate, functional and fair.

PMID- 16789668
TI  - Traumatic amputations.

PMID- 16789669
TI  - Embracing the problem of obesity.

PMID- 16789670
TI  - Rehabilitation nursing reaches across cultural barriers.

PMID- 16789671
TI  - Interventions to reduce back pain in rehabilitation hospital nursing staff.

PMID- 16789672
TI  - Life purpose: effect on functional decline and quality of life in polio
      survivors.
AB  - This article explores the protective effects that finding a purpose in life has
      on the level of physical and mental impairment and overall quality of life.
      Results were gathered from a national sample of 2,153 polio survivors. Although
      the combined social and physical experience of living with the disabling effects
      of polio has been associated with accelerated aging due to an increased
      allostatic load, finding a purpose in life may diminish these effects. The
      findings of this study indicate that purpose in life is associated with less
      perceived decline in health. Moreover, purpose in life is predictive of better
      quality of life despite levels of physical and mental impairment. Rehabilitation
      nurses should consider ways to help persons with polio maintain activities and
      interests that promote their sense of purpose in life.

PMID- 16789673
TI  - How cardiac rehabilitation relates to quality of life.
AB  - The purpose of this study is to determine the relationship between adherence to
      cardiac rehabilitation (CR) and improvements in health-related quality of life
      (HRQL) with a 12-week, Phase-II CR program. Previously collected data from 153 CR
      patients (114 males, 39 females; 69.1 years of age +/- 11.5) were utilized to
      complete this retrospective study. Patients completed the Medical Outcomes Survey
      Short Form-36 to assess HRQL at the beginning of CR (N = 153), at 3 months (N =
      152), and at 1 year (N = 94). Pearson correlation coefficients were generated to
      assess the relationship between CR attendance and HRQL. Paired sample t-tests
      helped determine the effect of CR on HRQL at 3 months and 1 year. No relationship
      was found between CR adherence and improvements in HRQL. Significant improvements
      in HRQL were found among all patients from baseline to 3 months and 1 year. Study
      findings demonstrate the effectiveness of CR in improving patient short- and long
      term HRQL regardless of patient adherence rate.

PMID- 16789674
TI  - Intrathecal baclofen therapy: challenges in patients with multiple sclerosis.
AB  - Intrathecal baclofen (ITB) is a recognized therapy for severe spasticity of both
      spinal and cerebral origin, with documented positive clinical outcomes for many
      patients with multiple sclerosis (MS). This article reviews some specific
      considerations concerning the use of ITB in the MS population, based on the
      author's 10 years of clinical experience. The unpredictable and progressive
      nature of the disease affects the identification of appropriate goals, the
      patient's decision-making process, and the evaluation of the response to the
      treatment over time. Patients with MS may be more sensitive to intrathecal
      baclofen than patients with other diagnoses, and may need a lower dose for both
      the screening test and maintenance therapy. Subtle cognitive changes may affect
      the patient's ability to understand the education needed for successful
      management of ITB. Some practical strategies are offered for the nurse involved
      in the care of these patients in each stage of the therapy.

PMID- 16789675
TI  - Problems of new caregivers of persons with stroke.
AB  - Nine adult caregivers new to the role of caring for persons with stroke, upon
      discharge from rehabilitation centers in Ohio and Michigan and living farther
      away from formalized support services than urban caregivers, were enrolled for 3
      months in a Web-based intervention project that examined the feasibility of the
      intervention and described the experience of caring. This article is an analysis
      of qualitative data from the intervention project that used a rigorous protocol
      to examine 68 perceived problems reported in caring. Problem themes in order of
      most to least frequent were 1) having independence issues, 2) dealing with
      emotions, 3) living with physical limitations, 4) managing co-morbid conditions,
      5) balancing it all, 6) participating in physical therapy, and 7) having sleeping
      issues. These problems were related to four of Orem's universal self-care
      requisites. Although the total number of problems decreased over time, "balancing
      it all" was the only problem that increased. This may be due to the resumption of
      the caregivers' regular activities or increased caregiving responsibilities.
      Nurses could use these findings to identify and focus on self-care needs of
      caregivers and to implement problem-resolution strategies.

PMID- 16789676
TI  - The prevention of disablement: A framework for the breast cancer trajectory.
AB  - More than 2 million women in the United States are breast cancer survivors. This
      is largely due to advances in early detection and treatment and is underscored by
      a survival rate of 88% at 5 years postdiagnosis for all stages of breast cancer.
      Although much progress has been made in combating the disease, women diagnosed
      with breast cancer endure multiple assaults to the body both from the disease and
      treatments. Surgical and adjuvant therapies are associated with complications and
      side effects that may lead to functional limitations, disability, and a poor
      quality of life. The Model of Disability and Disability Prevention provides a
      framework for addressing the challenges of the breast cancer trajectory. From
      pathology to disability, the model offers an approach to preventative and
      restorative interventions. Exercise is highlighted as an intervention that
      significantly affects the breast cancer experience at multiple points along the
      disablement continuum.

PMID- 16789677
TI  - Is there a future for the not-for-profit hospital?
AB  - The issue of the future of the not-for-profit hospital is not one of not for
      profit versus investor owned, but of economic viability. A shift toward business
      practices in the not-for-profit hospital is occurring and may help explain why
      few studies have been able to show distinctive differences between not-for-profit
      and investor-owned hospitals. Although the system is set up to give not for
      profits special privileges for promoting a societal common good, a gradual
      erosion of those privileges has blurred the distinction between the two types of
      entities. With a process I call "competitive advantage incrementalism," investor
      owned hospitals chip away at the privileges afforded their tax-exempt
      competitors. At the same time, the not-for-profit hospitals increasingly adopt
      the successful practices of the business world, and are guided by board members
      and executives who hold to a big-business view of healthcare. What is the future
      for the not-for-profit hospital? They must continue to exist, although they can
      expect increasing operating burdens to continue as not for profits. They and
      investor-owned facilities become progressively more similar in operations and
      structure. The not-for-profit institutions must prove that they produce a
      community benefit to justify not-for-profit status. That is a heavier burden than
      merely producing a high rate of return for investors.

PMID- 16789678
TI  - Not-for-profits: business basics for survival.
AB  - Many not-for-profit hospitals are struggling to keep their doors open. Although
      executives often contend that they are not playing on a level field, the
      fundamental cause is the hospital's failure to earn an excess of revenue over
      expenses. The tax exemption enjoyed by a not for profit can be a tremendous
      advantage. Some may argue that uncompensated care negates that benefit, but
      uncompensated care is a problem for the industry, not just not-for-profit
      institutions. The real issue at stake is the not-for-profit mentality--a belief
      that a tax-exempt business is not supposed to make money. On the contrary, our
      goal is to provide much-needed services to the community, and to do that well, we
      must make money. When solid business practices are followed, a hospital will be
      able to provide the basic healthcare services needed with positive financial
      results.

PMID- 16789679
TI  - The canary in the coal mine.

PMID- 16789680
TI  - Community benefit plans and action.
AB  - The tax-exempt sector in America is significant, and not-for-profit healthcare is
      its largest component. The basis for not-for-profit hospitals' tax exemption is
      not only "charity care" but the broader "community benefit." Community benefit
      planning and reporting offers a significant positive opportunity for not-for
      profit hospitals. Such planning allows a not-for-profit institution to:
      differentiate from the investor-owned hospital; re-focus on the local hospital
      and the benefit it brings to the community; change the public's perception of the
      value of the hospital; and regain public support by leading many of the community
      benefit programs addressing community needs. As Weckwerth suggested in his paper,
      regaining the public's trust needs to be done through action and not just words.
      The most effective action a not-for-profit hospital can take is to develop a
      sound, logical community benefit plan; carry out that plan; achieve benefits for
      the community through the plan's programs; and then widely report the
      accomplishments of the community benefit programs throughout the community. Then,
      the hospital should do it again and again, year after year. Although the
      financial stability of the not-for-profit hospital is important, far more
      important at this time is regaining the public's trust through demonstration of
      the many community benefits gained from having a local, not-for-profit hospital.

PMID- 16789681
TI  - Not-for-profit survival in a competitive world.

PMID- 16789682
TI  - The promise of evidence-based management.

PMID- 16789683
TI  - [Embryo and fetal pathology in routine diagnostics: what has changed and what
      needs to be changed].
AB  - The Authors have focused on the most important feto-neonatal and placental
      diseases in order to develop modern diagnostic tools which can meet the needs of
      clinicians (obstetricians, gynecologists, and neonatologists) for the best
      possible management of both the mother and the newborn. Although far from being
      operational instructions, it should be intended as a programmatic document
      providing a guideline on the issues that have cropped up in eight years of work
      of the APEFA group, as well as during several residential and practical classes.
      First of all, a synopsis is provided of the main issues concerning placental
      diagnosis in the newborn, as well as in case of fetal loss. A reasoned review is
      then provided of the main diagnostic criteria in placental pathology, in the
      light of therapeutical measures toward the mother (monitoring of future
      pregnancies) and the newborn (management of newborns at risk or with infectious
      disease). Legal issues in case of fetal distress at the end of pregnancy,
      neonatal damage and peripartum death have also been discussed with particular
      attention. Early and late miscarriages have also been separately examined, as
      well as fetal deaths. For each of these categories, a critical analysis is
      presented of current issues, followed by some considerations on the development
      of diagnostic methods and technology, and a modern diagnostic process is then
      outlined. Reference tables are also provided for diagnostic, auxological
      parameters, as well as on essential procedures. Issues concerning legal abortions
      and terminations of pregnancies have also been considered, with particular
      reference to tests and supplemental genetic and ultrasound examinations,
      diagnostic questions about malformations and forensic medicine assessments that
      are often involved with these specific categories. Malformations, fetal distress
      and growth retardation, sudden fetal and neonatal death, as well as embryo
      pathology are all briefly dealt with also with synoptic tables. Diagnostic
      criteria are thus optimized and specially aimed at solving "human reproduction
      pathology" issues.

PMID- 16789684
TI  - [The Haemolymphopathology Italian Group (H.I.G.): an essential resource for the
      new technical and organization problems troubling modern haemolymphopathology
      diagnostics].
AB  - Recently, many progresses have been recorded in the molecular and histogenetic
      characterization of the haematopoietic and lymphoid tumours, resulting in
      important classifying changes. As a consequence, the exact definition of lymphoma
      subtype requires an integration between traditional morphologic "expertise" and
      several bio-functional data obtained from advanced and complex ancillary
      techniques (immunohistochemistry, molecular biology and cytogenetics). At the
      same time, the data provided by gene expression profiling studies are going to
      deeply modify the therapies in haematological cancers. These studies are expected
      to allow the achievement of single-patient-tailored genic therapy; for this
      reason it is necessary to get biological samples of good quality. Indeed, while
      these progresses contribute to highlight the pathologist's diagnostic role, they
      should make us reflect on the state of the art of the Italian
      haemolymphopathology diagnostics and on its ability to cope up with the new
      challanges. The aim of this article is to outline a realistic picture of the
      present condition, and to explain the reasons for setting up, inside SIAPEC-IAP,
      the Haemolymphopathology Italian Group (H.I.G.). The purpose of H.I.G. will be
      twofold: first of all, scheduling of a series of projects so as to the
      haemolymphopathological diagnostic standardization; secondly, building a national
      network among all the pathologists involved in this exciting and complex field of
      the anatomic pathology.

PMID- 16789685
TI  - [Mature cystic teratoma of the ovary with a small ganglioneuroma].
AB  - A case of ganglioneuroma arising within a cystic mature teratoma of the ovary in
      a 34-year-old woman is reported. Patient underwent right adnexectomy. The ovary
      was completely replaced by a bilocular cystic lesion, measuring 8 cm in diameter
      and filled with adipose tissue and pilosebaceous material. Microscopically the
      cyst was composed by a mature cystic teratoma containing skin with dermal
      appendages, fatty tissue and bronchial epithelium. Furthermore a nodule (0.5 cm
      in size) composed of mature ganglion cells, axons and Schwann cells, was
      identified. Ganglion cells were positive for NSE and synaptophysin, while Schwann
      cells stained positively with S100 protein and GFAP. To the best of our
      knowledgment this is the first reported cases of ganglioneuroma arisen within a
      cystic mature teratoma of the ovary.

PMID- 16789686
TI  - [Recurrent intraparenchimal haemorrhages in a patient with cerebral amyloidotic
      angiopathy: description of one autopsy case].
AB  - Cerebral amyloidotic angiopathy represents the most frequent cause of lobar
      haematoma in young patients and represents 5-10% of the non-traumatic cerebral
      haemorrhages. In the present work, we describe one autoptic case of recurrent
      cerebral haemorrhages in a 58-year-old woman. Macroscopically in the brain
      multiple haemorragic areas were present in the right frontal pole, right frontal
      and temporo-parietal lobes with homolateral ventricular inundation. The
      histological, histochemical, immunohistochemical, ultrastructural and
      biomolecular investigations confirmed the presence of amyloid deposits in the
      middle-size and little-size cerebral arteries. We report, moreover, a novel
      mutation (Leu705Val) within the Abeta sequence of a AbetaPP in a family with
      autosomal dominant, recurrent intracerebral hemorrhages beginning in the sixth
      decade of life.

PMID- 16789687
TI  - [Dental pulp metastasis from oral squamous cell carcinoma: a case report and a
      review of the literature].
AB  - A 61-year-old man was seen in the Oral Pathology Department with a three-month
      history of right mandibular pain. Clinical examination revealed a 3 cm mass
      involving the body and the angle of the right site of the mandible and palpable
      masses in the neck. The dental panoramic radiography showed on the right a
      radiolucenT area surrounding the lower second molar, extending to the mandible
      angle. Additionally, chest radiograph and routine laboratory analysis results
      were unremarkable. An incisional biopsy of the area, revealed histologically a
      well differentiated squamous cell carcinoma and after few days, the patient
      received a right hemimandibulectomy with dissection of submandibular salivary
      gland and laterocervical lymph nodes on the same side. The histology of surgical
      material confirmed the diagnosis of a differentiated squamous cell carcinoma G1,
      homolateral diffusion in the mandible bone and metastasis to the dental pulp of
      the second lower molar tooth and to one of 18 lymph nodes dissected. In this
      report is described a very rare metastasis to the dental pulp and literature
      review, in which only fifteen other cases are reported.

PMID- 16789688
TI  - Making ERP work. Healthcare providers are taking a closer look at enterprise
      resource planning.

PMID- 16789689
TI  - Wiring for health. Privacy is paramount, as the House of Representatives looks at
      e-health bill.

PMID- 16789690
TI  - The hits just keep on coming. The pace of M&A activity in the healthcare IT space
      continues to accelerate.

PMID- 16789691
TI  - Brailer's farewell. Interview by Charlene Marietti.

PMID- 16789692
TI  - Search for the single sign-on. Ball Memorial is working to provide access to
      patient information in a flexible, centralized work environment.

PMID- 16789693
TI  - Freedom of choice. For real consumer-directed healthcare, patients must have
      solid information at their fingertips.

PMID- 16789694
TI  - Geisinger and the MPI. Geisinger is leveraging Sun SeeBeyond for its master
      patient index.

PMID- 16789695
TI  - Location, location, location. Denver Health decided to get a better handle on its
      clinical equipment with location tracking software.

PMID- 16789696
TI  - Surgery suite to support safety. CHW Sacramento-area hospitals identify real time
      clinical documentation and robust reporting as essential.

PMID- 16789697
TI  - Advanced practice: implications for clinical and procurement transplant
      coordinators.
AB  - What is exciting about the "buzz" is that it is encouraging continuing education
      and knowledge acquisition. Advanced practitioners, including clinical and
      procurement transplant coordinators, have recognized the need to continually
      enhance their knowledge base, formally and informally. Whether procurement or
      clinical, transplant coordinators function in expanded roles by virtue of their
      knowledge and skills. They have been practicing at that high level with
      specialized, complex skills and knowledge for at least 30 years. Advanced
      practice is what procurement and clinical transplant coordinators do. We have met
      the advanced practice transplant coordinator, and we are him or her.

PMID- 16789698
TI  - Evaluating patients with a criminal history.

PMID- 16789699
TI  - Posttransplant diabetes mellitus in liver transplant recipients.
AB  - CONTEXT: Approximately 20% of liver transplant recipients develop posttransplant
      diabetes mellitus. Hepatitis C, a leading indication for liver transplantation,
      has been identified as a risk factor for posttransplant diabetes mellitus and is
      an observation that is not well described. OBJECTIVE: To evaluate the incidence
      of posttransplant diabetes mellitus and risk factors associated with this
      condition. DESIGN: A retrospective chart review. SETTING: A large urban
      transplant center. PATIENTS: One hundred fifteen liver transplant recipients who
      received a transplant between January 1, 1998, and August 31, 2001. RESULTS: The
      rate of posttransplant diabetes mellitus, calculated at 3-month intervals in the
      first year after liver transplantation, ranged from 19.4% to 24.6%, which is
      similar to the averages reported in most published studies. The cumulative rate
      of posttransplant diabetes mellitus, which includes all patients who developed
      this condition during the time studied, was 31.3%. Clinical and demographic
      factors, including immunosuppression regimens, were similar between patients with
      and without posttransplant diabetes mellitus. Two risk factors for posttransplant
      diabetes mellitus were identified: hepatitis C, which was the leading indication
      for transplantation in this group (54.8%), and cytomegalovirus infection during
      the first year after transplantation. Other clinical and demographic variables,
      such as gender, age, ethnicity, rejection episodes, body mass index, and
      immunosuppression, were not identified as risk factors for posttransplant
      diabetes mellitus in liver transplant recipients.

PMID- 16789700
TI  - Evidence on spouse responses to illness as a guide to understanding and studying
      spouse responses to living organ donation.
AB  - Although living kidney donors receive praise from friends and coworkers for their
      selflessness, recent studies report that members of the immediate family may not
      be as supportive. Reports of conflict surrounding living organ donation include
      divorce between the donor and the donor's spouse. The purpose of this review of
      the literature is to (1) discuss the spousal role when confronted with a
      partner's illness, (2) explore the current research describing the spouses of
      patients with heart disease and cancer, various transplant recipients, and living
      organ donors, and (3) identify the need for future research to explore the
      experiences and needs of the spouses of living kidney donors. Because the
      attitudes of donor family members, especially spouses, may affect the decision to
      donate and the satisfaction with recovery from donation surgery, it is critical
      to know how the spouses of living kidney donors view kidney donation. This
      knowledge may be instrumental in promoting family harmony and donor recovery and
      wellness.

PMID- 16789701
TI  - Reproduction and pregnancy in transplant recipients: current practices.
AB  - Many transplant physicians are faced with questions from their patients about the
      safety and long-term consequences of pregnancy following transplantation. To
      better understand how pregnancies are managed and to clarify the outcome of
      pregnancy after transplantation, a survey questionnaire was developed and mailed
      to all medical and surgical directors of transplant centers throughout the United
      States; responses were obtained from 59.1% of the transplant centers. Although
      many opinions were collected, most respondents conceded that their opinions were
      based on personal experience rather than evidence-based. The underutilization of
      existing information was revealing and highlighted a need for an evidence-based
      approach to care of the pregnant transplant recipient and her offspring. The
      survey results, reported in this article, led to formation of a consensus
      conference to determine the optimal approach to pregnant transplant recipients
      and to define what is currently known and unknown about reproduction and
      transplantation.

PMID- 16789702
TI  - BK virus infection in kidney transplantation: a case for early intervention.
AB  - The prognosis for renal allograft survival in a patient with BK virus-associated
      nephropathy is distressing because nearly 50% of affected grafts are lost. With
      these statistics in mind, attempting clinical intervention before BK virus
      disease develops seems appropriate. Noninvasive screening tools such as tests to
      detect decoy cells in urine can enable diagnosis of BK viral infection in its
      early stages. Although it is not entirely clear which patients with BK infection
      will have BK disease develop, it may be possible to intervene in this early
      warning period to prevent the further development of BK virus-associated
      nephropathy. We present a case of a 50-year-old man in whom asymptomatic BK
      viruria developed 6 weeks after he received a non-HLA matched kidney from a
      deceased donor. This BK viruria was accompanied, subsequently, by an unexplained
      increase in serum creatinine level 2 months after transplantation. Following a
      change in his immunosuppressive regimen as therapy for presumed renal allograft
      dysfunction associated with BK viral infection, the decoy cells in his urine
      disappeared and his creatinine levels stabilized.

PMID- 16789703
TI  - Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in
      patients with gastrointestinal side effects: case studies.
AB  - BACKGROUND: The potential benefit of the current mycophenolic acid, mycophenolate
      mofetil, has not yet been fully achieved in clinical transplantation because of
      its gastrointestinal side effects. Dose splitting, dose reduction, and drug
      discontinuation are strategies that are used to manage gastrointestinal symptoms.
      However, recently reported registry data suggest these alterations result in
      inadequate graft protection, leading to increased late acute rejection rates and
      decreased longterm graft survival. OBJECTIVE: To investigate the potential use of
      the new enteric-coated formulation of mycophenolic acid therapy, mycophenolate
      sodium, and its suggested improved side effects profile. PARTICIPANTS: Five
      patients who previously had or were currently experiencing gastrointestinal side
      effects while taking mycophenolate mofetil were selected at random. These
      patients were initially switched to an equimolar dose of enteric-coated
      mycophenolate sodium. An increase in mycophenolate sodium doses was attempted
      according to symptoms. Changes in kidney function and gastrointestinal symptom
      scores were recorded before and after conversion. RESULTS: No episodes of acute
      rejection were observed in any patients during or after conversion. All patients
      experienced an overall improvement in gastrointestinal symptom scores following
      conversion, and an increase in mycophenolate sodium dose was achieved in 1
      patient.

PMID- 16789704
TI  - Donation after cardiac death has a minimal impact on thoracic organ recovery.
AB  - BACKGROUND: Our organ procurement organization recently developed an aggressive
      donation after cardiac death program. Thoracic organs are rarely recovered from
      non-heart-beating donors. Therefore, there is concern that donation after cardiac
      death may affect the recovery of thoracic organs from donors not allowed to
      progress to brain death. OBJECTIVE: To evaluate the potential impact of donation
      after cardiac death on the recovery of thoracic organs. METHODS: On the
      assumption that prolongation of care on all cases would result in a diagnosis of
      brain death. By retrospective chart review, all donations after cardiac death
      were evaluated for thoracic organ potential using the same standards that were
      used to evaluate brain-dead donors. RESULTS: During the study period there were
      34 of 44 (77%) non-heart-beating donors qualified to donate abdominal organs
      only. Ten of 44 non-heart-beating donors (24%) qualified to potentially donate
      thoracic organs; the families of 4 of 10 of these donors insisted on the
      immediate withdrawal of life support, leaving only 6 donors with thoracic organ
      potential. All 6 of these donors qualified as potential heart donors and 3 as
      potential lung donors. CONCLUSIONS: A total of 97 organs were recovered and
      successfully transplanted from 44 non-heart-beating donors. If all the donors who
      qualified to donate thoracic organs progressed to brain death and if their
      thoracic organs were transplantable, then 6 additional hearts and 3 pairs of
      lungs may have been recovered. These data demonstrate that an aggressive donation
      after cardiac death program contributes significantly to the organ donor pool,
      with a minimal impact on potential thoracic organ recovery.

PMID- 16789705
TI  - Information sharing: its impact on donor and nondonor families' experiences in
      the hospital.
AB  - OBJECTIVE: To illustrate the methods used to convey complicated information
      regarding the critical injury, and death diagnosed by means of brainstem testing,
      to the next of kin of potential organ donors. DESIGN: 3-year, prospective,
      longitudinal study. PARTICIPANTS AND SETTING: Forty-three family members who
      chose to donate their deceased relatives' organs were recruited via 4 transplant
      coordinating centers, and 3 family members who chose not to donate were recruited
      via 1 intensive care unit. METHOD: Face-to-face qualitative interviews were
      carried out with 46 family members of 43 individuals who died between June and
      December 2000. Family members who agreed to donation were interviewed during and
      after their next of kin's admission to hospital and 3 to 5 months, 13 to 15
      months, and 18 to 26 months after bereavement. Three participants who chose not
      to donate were interviewed on 1 occasion only. Interviews were audio-recorded,
      and the transcribed reports were analyzed using a comparative, thematic approach
      focusing on the detection of similarities and differences between cases. RESULTS:
      Participants who were offered verbal information supported by complementary
      methods of communication had (1) a greater understanding of the critical injury
      sustained by their next of kin, and (2) fewer questions over time regarding
      brainstem testing. CONCLUSION: Better methods of communicating complicated
      information are needed, as the sheer load of information shared makes demands of
      next of kin at a time when they are cognitively and emotionally poorly equipped
      to respond.

PMID- 16789706
TI  - Family responses to donor designation in donation cases: a longitudinal study.
AB  - CONTEXT: A 2001 state law reinforced donors' rights by mandating that donor
      consent be strictly honored. One concern was the potentially negative impact of
      donor designation notification on donor families. OBJECTIVES: To examine donor
      families' responses to donor designation. DESIGN: Descriptive nonexperimental
      design spanning July 1999 to September 2004. SETTING: State served by organ
      procurement organization. DATA: Results from surveys completed by 569 donor
      families, including 162 surveys from designated donor families. MAIN OUTCOME
      MEASURES: Previous discussions, designation awareness, information helpful,
      information stress, awareness of meaning of donation, and comfort with
      designation decision. RESULTS: The majority (79%) of designated donor families
      reported their loved ones had discussed donation with them; of these families,
      86% were aware of donor designation, and 83% understood what donation entailed.
      The majority (75%) thought information about loved ones' donor designation was
      helpful, and only 8% found it stressful. In contrast, 18% of families of
      nondesignated donors said being approached about donation was stressful after the
      law was strengthened. However, over 80% of all donor families were comfortable
      with the donation decision. CONCLUSIONS: The results fail to support the
      assumption that donor families perceive donor designation notification as
      negative and stressful. The majority of designated donor families report relief
      and reduced stress, compared to families approached for donation. The findings
      suggest that strengthening donor designation legislation can lead to positive
      results for donor families and donation recipients.

PMID- 16789707
TI  - Advanced practice organ procurement techniques: insertion of central venous
      catheters.
AB  - Placement of central venous catheters by organ procurement coordinators to assist
      in obtaining blood samples or for measuring intravascular pressure is
      appropriate. Preparation for this role should include appropriate didactic
      instruction and supervised clinical experience. The organ procurement
      organization must ensure that such training occurs and must support a continuing
      quality assurance program for such providers. Policies and procedures must be
      provided to guide practitioners in site selection, timing of implementation, and
      titration of measurements obtained. Also, resources must be readily available to
      treat any complications. This discussion reviews methods for insertion of venous
      catheters placed in the femoral, internal jugular, or subclavian veins.

PMID- 16789708
TI  - Patient-reported outcomes for open versus laparoscopic living donor nephrectomy.
AB  - BACKGROUND: Rates of living kidney donation have increased dramatically in recent
      years, in large part because of improved surgical techniques such as laparoscopic
      nephrectomy. OBJECTIVE: To compare patient-reported outcomes of laparoscopic
      nephrectomy versus open donor nephrectomy in 84 adult live kidney donors. OUTCOME
      MEASURES: Outcomes included perceptions of pain and surgical scarring, number of
      surgical/medical complications, hospital length of stay, physical health problems
      related to donation, return to work, financial impact, health-related quality of
      life, and satisfaction with the donation experience. RESULTS AND CONCLUSION: The
      2 groups did not differ significantly in pain perceptions, number of
      surgical/medical complications, physical health problems, financial impact,
      health-related quality of life, or overall satisfaction. However, laparoscopic
      nephrectomy donors had significantly fewer hospital days and faster return to
      work time than open donor nephrectomy donors. The majority of donors report
      excellent health-related quality of life and no complications in the months
      following surgery. In addition, it appears that laparoscopic nephrectomy, in
      comparison to open donor nephrectomy, may reduce barriers to living kidney
      donation by reducing hospital length of stay and time away from work. Being able
      to return to work much sooner after surgery may significantly reduce the indirect
      costs (ie, lost wages) associated with living donation.

PMID- 16789709
TI  - Is it ethical to prioritize patients for organ allocation according to their
      values about organ donation?
AB  - Because the supply of deceased donor organs fails to meet demand, patients
      needing a transplant frequently have lengthy waits or die while waiting. In an
      effort to reduce waiting times, the concept of "preferred status" has emerged. In
      the United States, preferred status has taken the form of a community of
      individuals called LifeSharers. Using directed donation, this group aims to
      facilitate priority organ allocation to its members-people who have agreed to be
      organ donors. Such preferred status programs increase societal awareness about
      organ donation and transplantation, but they are not without ethical controversy,
      as some term them "clubs." In the case of LifeSharers, the potential to increase
      the pool of deceased donor organs is a worthy goal that would benefit the
      community of patients awaiting transplantation, not just LifeSharers members.

PMID- 16789710
TI  - Use of age and milk production data to improve the ability of enzyme-linked
      immunosorbent assay test results to predict Mycobacterium avium ssp.
      paratuberculosis fecal culture status.
AB  - Cows from 2 California dairies were tested for paratuberculosis at the end of
      lactation by using fecal culture and a commercially available serum enzyme-linked
      immunosorbent assay (ELISA) test kit. Individual cow characteristics and
      production variables were evaluated along with ELISA testing results as
      predictors of fecal culture status. In multivariable logistic regression
      analysis, age and a herd-standardized version of 305-day mature equivalent (305
      ME) milk production were significant predictors of fecal culture status after
      adjusting for herd, quarter of the study year, and ELISA sample-to-positive (S/P)
      ratio. The area under a nonparametric receiver operating characteristic curve was
      significantly greater for a multivariable model that included age and the level
      of milk production when compared with a model without these covariates. In
      conclusion, consideration of cow-level covariates was useful as an aid in
      predicting Mycobacterium avium ssp. paratuberculosis (MAP) fecal culture status.
      For a given ELISA S/P ratio, older cows and those with lower 305 ME milk
      production relative to other cows in the herd were significantly more likely to
      be shedding MAP in their feces at the end of lactation.

PMID- 16789711
TI  - Comparison of the recovery of Mycobacterium bovis isolates using the BACTEC MGIT
      960 system, BACTEC 460 system, and Middlebrook 7H10 and 7H11 solid media.
AB  - The BACTEC Microbacteria Growth Indicator Tube (MGIT) 960 system was evaluated to
      determine how it compares with the BACTEC 460 radiometric system and solid media
      for recovery of Mycobacterium bovis from tissue samples. A total of 506 bovine
      lymph node samples were collected from abattoirs in the United States and Mexico
      between November 2003 and September 2004. Processed samples were inoculated into
      an MGIT 960 tube, BACTEC 460 vial, and Middlebrook 7H10 and Middlebrook 7H11
      solid media. Ziehl-Neelsen slides were prepared to check for contaminants and
      confirm the presence of acid-fast positive bacilli. Samples containing acid-fast
      bacilli were confirmed as members of the Mycobacterium tuberculosis complex by a
      nucleic acid assay. Niacin and nitrate biochemical tests were used to distinguish
      M. bovis from M. tuberculosis isolates. Statistical analyses were performed to
      compare recovery rate, mean time to detection, contamination rates, as well as
      pair-wise comparisons in each category. The results showed that the MGIT 960
      system had a higher recovery rate of M. bovis (122/129) than did the BACTEC 460
      (102/129) and solid media system (96/129). The average time to detection was 15.8
      days for the MGIT 960 system, 28.2 days for the BACTEC 460 system, and 43.4 days
      for solid media. Contamination rates were 6.9% for the MGIT 960 system, 3.4% for
      the BACTEC 460 system, and 21.7% for solid media. These results indicate the MGIT
      960 system can be used as an alternative to the BACTEC 460 system for recovering
      M. bovis from tissue samples.

PMID- 16789712
TI  - Evaluation of nephelometry for albumin measurement in serum and cerebrospinal
      fluid: experiences with an indwelling subarachnoidal catheter system for
      repetitive cerebrospinal fluid collection in horses.
AB  - The measurement of albumin concentrations in cerebrospinal fluid (CSF) and serum
      for albumin quotient (AQ) calculations in normal horses was performed by 2
      methods: 1) total protein measurement, followed by electrophoresis of the samples
      to obtain an albumin percentage; and 2) albumin immunoprecipitation quantitated
      by nephelometry. The results of both methods correlated well, and nephelometry
      was chosen to determine the albumin concentrations in CSF samples obtained from
      an indwelling subarachnoidal catheter for daily sampling. Because the use of an
      indwelling catheter to collect repetitive CSF samples is a novel technique,
      routine cytological CSF analysis was performed along with daily clinical
      evaluation to ascertain the well-being of the horses. The catheters were placed
      in 2 horses for periods of 14 and 17 days. One horse exhibited pleocytosis on
      cytological evaluation of CSF on 2 occasions for a 1-2-day duration; however, the
      AQ showed a significant increase on only 1 occasion. The other horse had a normal
      cell count in CSF but showed 2 sudden changes in the AQ value; however, these
      values remained within the 95% confidence interval for AQ in horses. Albumin
      quotient values of the second horse were consistently below the lower range of
      the confidence interval. Results from this study indicate that nephelometry can
      be used for albumin determination in serum and CSF samples from horses.
      Furthermore, an indwelling subarachnoidal catheter system can provide serial CSF
      samples in horses, thus obviating the need for repetitive centesis for serial CSF
      sampling.

PMID- 16789713
TI  - Rapid, multiwell colorimetric assay for measuring neutrophil chemoattractant
      activity in bronchoalveolar lavage fluid of horses with recurrent airway
      obstruction.
AB  - The criteria used to diagnose recurrent airway obstruction (RAO) in affected
      horses include demonstration of reversible lower airway obstruction and greater
      than 25% neutrophils in bronchoalveolar lavage fluid (BALF). Additional objective
      laboratory tests are needed to improve diagnostic accuracy and to monitor
      response to treatment. The goal of this study was to determine if neutrophil
      chemoattractant activity of BALF could be measured by using a previously
      described, rapid, multiwell colorimetric assay for chemotaxis. In this assay,
      neutrophils that have migrated through a membrane filter are collected into the
      bottom well of a disposable chemotaxis-cell migration chamber. The number of
      viable cells collected in the bottom well is quantified by measurement of the
      reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide (MTT),
      which is reduced by dehydrogenase in mitochondria of live cells. The number of
      migrating cells corresponds to the amount of MTT reduced, which is measured with
      an enzyme-linked immunosorbent assay plate reader. Fourteen adult horses were
      enrolled in this study, 7 of which had owner histories consistent with RAO. Each
      horse was sedated, a bronchoalveolar lavage tube was passed, and saline was
      infused and immediately aspirated. An aliquot of BALF was used for differential
      cell count, and BALF supernatant was harvested to assess neutrophil
      chemoattractant activity. Normal control horses and RAO-affected horses were
      distinguished according to clinical signs and percent neutrophils in BALF.
      Neutrophil chemoattractant activity of BALF was significantly greater in RAO
      affected horses (P = 0.001) compared with control horses. This assay may be
      useful in future studies for monitoring response to therapy in RAOaffected
      horses.

PMID- 16789714
TI  - Inability of kaolin treatment to remove nonspecific inhibitors from equine serum
      for the hemagglutination inhibition test against equine H7N7 influenza virus.
AB  - The hemagglutination inhibition test is used by many diagnostic and surveillance
      laboratories for detection of antibodies to influenza viruses. It is well known
      that the hemagglutination inhibition test is affected by nonspecific inhibitors
      present in equine serum. Several serum treatments are in use to remove these
      inhibitors, including treatment with kaolin. Discrepant results were observed in
      the authors' laboratories when using kaolin treatment before testing equine sera
      for antibodies against equine influenza virus (EIV) subtype-1 (H7N7). It is
      demonstrated here that kaolin treatment leads to false positive results when
      testing for antibodies against EIV subtype-1, as compared to other standard serum
      treatments (trypsin-periodate, receptor-destroying enzyme). Against EIV subtype-2
      (H3N8), however, false positive results were not evident. Trypsinperiodate and
      receptor-destroying enzyme (RDE) treatments appear to be superior to kaolin for
      removal of nonspecific inhibitors from equine serum and should be used for
      serological diagnosis and surveillance of equine influenza virus.

PMID- 16789715
TI  - Application of a dot enzyme-linked immunosorbent assay for evaluation of the
      immune status to canine parvovirus and distemper virus in adult dogs before
      revaccination.
AB  - A growing body of literature has been published indicating that the current
      practice of annual vaccination of dogs may not be beneficial and in some cases
      may even be harmful. A number of publications have proposed assessing the immune
      status of dogs before annual revaccination. In this study the usefulness of a
      commercially available dot-ELISA kit was evaluated to determine the duration IgG
      antibody titers to canine parvovirus (CPV) and canine distemper virus (CDV) in
      158 dogs vaccinated at least one year ago. Overall, the percentage of dogs with
      protective antibody titers to both CPV and CDV was 84%. The percentage of dogs
      with borderline antibody titers was 11% for CPV and 10% for CDV. Four percent of
      the dogs had no detectable antibody to CPV and 6% had no antibody to CDV. The
      results reported here are in good agreement with other studies measuring IgG
      antibody levels. It is concluded that the kit offers veterinarians the
      opportunity of determining antibody titers and revaccinating only those pets
      whose antibody titers to specific diseases have waned.

PMID- 16789716
TI  - Application of temperature-gradient gel electrophoresis for detection of prion
      protein gene polymorphisms in Polish Swiniarka sheep.
AB  - This study presents preliminary data on the polymorphism in the prion protein
      gene of Swiniarka sheep using temperature gradient gel electrophoresis (TGGE).
      Available data indicate that sensitivity to scrapie is associated with
      polymorphisms in three codons of prion protein gene: 136,154, and 171. The TGGE
      method was used to detect point mutations in these codons responsible for
      sensitivity or resistance to scrapie. This study revealed presence of an allele
      encoding valine (V) in codon 136, which is associated with high sensitivity to
      scrapie and occurred in the form of heterozygous allele together with alanine
      (AV). The highest variability was observed in codon 171, with presence of
      arginine (R) and glutamine (Q) in the homozygous (RR or QQ) as well as the
      heterozygous form (RQ). The results of examination of fifty sheep DNA samples
      with mutations in codons 136, 154, and 171 demonstrated that TGGE can be used as
      a simple and rapid method to detect mutations in the PrP gene of sheep. Several
      samples can be run at the same time, making TGGE ideal for the screening of large
      numbers of samples.

PMID- 16789717
TI  - Detection of early stages of Myxobolus cerebralis in fin clips from rainbow trout
      (Orynchus mykiss).
AB  - A nested polymerase chain reaction (PCR) assay was used to detect early stages of
      Myxobolus cerebralis in caudal and adipose fin samples from rainbow trout (RT).
      To determine sensitivity, groups of 10 RT were exposed to 2,000 M. cerebralis
      triactinomyxons/fish for 1 hour at 15 degrees C and subsequently moved to clean
      recirculating water. Fish were held for 2 and 6 hours and 1, 2, 3, 5, 7, 10, 30,
      and 60 days before sampling by nonlethal fin biopsy. Nested PCR performed on fin
      clips showed that M. cerebralis DNA was detected in caudal fin tissue in 100% of
      fish up to 5 days postexposure. At days 7 and 10 postexposure, 80% of fish were
      positive, and at 60 days postexposure, 60% of fish were positive using this
      technique. Conversely, testing on adipose fin clips proved less sensitive, as
      positive fish dropped from 80% at day 7 to below 20% at day 10 postinfection.
      Since detection of M. cerebralis infection using caudal fin samples coupled with
      nested PCR is an effective method for detection of early parasite stages, use of
      this technique provides for accurate, nonlethal testing.

PMID- 16789718
TI  - Multiplex reverse transcription-PCR for rapid differential detection of porcine
      epidemic diarrhea virus, transmissible gastroenteritis virus, and porcine group A
      rotavirus.
AB  - A novel multiplex reverse transcription polymerase chain reaction (multiplex RT
      PCR) that can detect porcine epidemic diarrhea virus (PEDV), transmissible
      gastroenteritis virus (TGEV), and porcine group A rotavirus (GAR) was developed.
      The 3 viruses (PEDV, TGEV, and porcine GAR) are major agents in viral enteric
      diseases of piglets. As the clinical signs of these diseases are similar,
      including watery diarrhea, differential detection is required for etiologic
      diagnosis. A mixture of 3 pairs of published primers was used for amplification
      of viral nucleic acids, yielding 3 different amplicons with sizes of 859 bp, 651
      bp, and 309 bp for TGEV, PEDV, and porcine GAR, respectively. A total of 157
      specimens (78 fecal and 79 intestinal samples) from piglets with acute
      gastroenteritis were collected in Korea between January 2004 and May 2005. They
      were tested for the presence of 3 viruses by multiplex RT-PCR. Coinfections with
      PEDV and porcine GAR were identified in 16 farms (43.2%). PEDV, porcine GAR, and
      TGEV infection were 26.3%, 13.2%, and 2.7% respectively. The relative sensitivity
      and specificity of multiplex RT-PCR were evaluated, with results suggesting that
      this assay is equal in quality to conventional single-agent RT-PCR assays
      (sensitivity:100%, 92.9%, 100% for TGEV, PEDV, GARs; specificity: 100% for all 3
      viruses). This multiplex RT-PCR is a simple assay and may be a potentially useful
      for rapid, sensitive, and cost-effective etiological diagnostic tool for acute
      viral gastroenteritis in piglets.

PMID- 16789719
TI  - Falcon adenovirus infection in breeding Taita falcons (Falco fasciinucha).
AB  - Four female and 3 male Taita falcons (Falco fasciinucha) out of a breeding colony
      of 14 Taita falcons (7 pairs) died during the breeding season after showing
      lethargy and anorexia for 1 to 2 days. All animals were submitted for necropsy.
      Gross lesions in the female falcons were characterized by anemia secondary to
      marked hemorrhage into the ovary and oviduct, serofibrinous effusion into the
      cardioabdominal cavity and serosal petechiae. In addition, marked necrotizing
      splenitis and pulmonary hemorrhage were present. Histologically, the female
      falcons had mild necrotizing hepatitis with numerous intranuclear inclusion
      bodies and necrotizing splenitis with rare inclusion bodies. There were no gross
      lesions in the male falcons, and the histological lesions were characterized by
      urate deposition and rare intranuclear inclusion bodies in the renal tubular
      epithelial cells. Adenoviral particles were found by electron microscopy in the
      cloacal contents of the female Taita falcons but not in the male falcons. DNA in
      situ hybridization revealed widespread aviadenoviral nucleic acid within the
      nuclei of hepatocytes, renal tubular epithelial cells, and adrenal cells in the
      female falcons but no aviadenoviral nucleic acid in 1 male falcon and only a low
      quantity of adenoviral nucleic acid in the liver and kidney of another male Taita
      falcon. PCR amplified aviadenoviral DNA in the liver and intestine of all Taita
      falcons. The amplicons were sequenced, and the virus was identified as falcon
      adenovirus. The deaths of the female and male birds were attributed to the
      aviadenovirus infection.

PMID- 16789720
TI  - Clinical, histopathological and immunohistochemical findings in a case of
      megakaryoblastic leukemia in a dog.
AB  - The clinical, hematological, and histopathologic features of megakaryoblastic
      leukemia (M7) were investigated in a 10-year-old female Shih-Tzu dog.
      Megakaryoblastic leukemia was diagnosed using anti-human platelet glycoprotein
      (GP IIIa) and anti-human von Willebrand factor (vWF) antibodies. The expression
      of CD antigen on megakaryoblasts was also assessed using a CD79a monoclonal
      antibody. Immunological markers allowed visualization of neoplastic
      megakaryocytes. Antibodies against platelet GP IIIa were demonstrated to be the
      most useful for the diagnosis of megakaryoblastic leukemia of paraffin-embedded
      canine tissues. Hematological and histological data coupled with
      immunohistochemical reactivity for platelet GP IIIa, vWF, and CD79a antigen in
      blast cells confirmed a diagnosis of M7 megakaryoblastic leukemia.

PMID- 16789721
TI  - Alpha-fetoprotein in serum and tumor tissues in dogs with hepatocellular
      carcinoma.
AB  - Serum alpha-fetoprotein (AFP) concentrations were measured before and after
      surgical removal of tumor masses in four dogs with hepatocellular carcinoma
      (HCC). Localization of AFP was also examined immunohistochemically in tumor
      tissues. In three cases, the serum AFP concentration was 10 to 20 times higher
      than that of normal dogs. One to two months after surgery, the serum AFP
      concentration had decreased to normal range. AFP was localized in the tumor
      tissues in these three cases. One case, which had a low serum AFP, did not show
      AFP localization in tumor tissue.

PMID- 16789722
TI  - Use of sentinel chickens to evaluate the effectiveness of cleaning and
      disinfection procedures in noncommercial poultry operations infected with exotic
      Newcastle disease virus.
AB  - The use of sentinel chickens in establishing the negative status of commercial
      poultry flocks depopulated due to exotic Newcastle disease (END) is considered to
      be an economically beneficial process. However, the costs and benefits of using
      sentinel chickens in noncommercial operations are in question. The objective of
      this study was to use sentinel chickens to evaluate whether adequate cleaning and
      disinfection coupled with an appropriate time period without susceptible poultry
      species on the premises would eliminate END virus from a noncommercial poultry
      operation and preclude the need for placement of sentinels in previously infected
      operations before declaring them free of virus. Noncommercial poultry operations
      were selected from the 2002 to 2003 END outbreak database. Operations included in
      the study had one or more isolations of END virus (ENDV) from cloacal or
      oropharyngeal swabs of birds on the premises. A total of 546 birds were placed on
      53 premises. All sentinel birds sampled after placements were negative by virus
      detection methods and serologic tests. Results of this study indicate that time
      and the application of appropriate cleaning and disinfection procedures will
      adequately mitigate the risk of viable virus persisting in noncommercial poultry
      operations. In the future, this information may eliminate the need for sentinel
      bird placement to ensure virus free status of premises before repopulation,
      thereby decreasing the costs of END eradication.

PMID- 16789723
TI  - Cerebellar degeneration in cattle grazing Solanum bonariense ("Naranjillo") in
      Western Uruguay.
AB  - Cattle in western Uruguay that were eating Solanum bonariense developed periodic
      episodes of ataxia, hypermetria, hyperesthesia, head and thoracic limb extension,
      opisthotonus, nystagmus, and falling to the side or backward. Similar clinical
      signs were experimentally reproduced in cattle by administration of S. bonariense
      via rumen cannula at a dose of 1,024 g/kg body mass. No significant gross lesions
      were observed in field cases or experimentally induced cases. Spontaneous and
      induced histologic lesions were similar and included vacuolation, degeneration,
      and loss of Purkinje cells. Axonal spheroids, microcavitations, and other changes
      of wallerian-type degeneration in cerebellar white matter were also observed.
      Ultrastructural changes included increased number of electron-dense residual
      storage bodies in membrane-bound vesicles in affected Purkinje cells, and similar
      vesicles and mitochondria in axonal spheroids. No histologic lesions were
      detected in the other examined tissues. The Purkinje-cell swelling and
      vacuolation with subsequent cerebellar degeneration are suggestive of Purkinje
      cell specific toxin that produces abnormal lysosome function and cell specific
      axonal transport. This is the first report of S. bonariense toxicity.

PMID- 16789724
TI  - Bilateral cystic rete testis in an alpaca (Lama pacos).
AB  - A 9-year-old intact male alpaca (Lama pacos) was examined because of marked
      enlargement of the left scrotum. Ultrasound examination revealed a thin-walled
      anechoic structure in the area of the left testis. Aspirated fluid contained
      spermatozoa, many of which had abnormal morphology. Castration was performed and
      the left testis was markedly enlarged with a clear fluid-filled cyst. The cyst
      was lined by a single layer of squamous to cuboidal epithelial cells consistent
      with those originating from rete testis. The right testis was of a comparable
      size and shape to that of normal alpaca testis, but the rete testis was mildly to
      moderately dilated. Additional findings included chronic inflammation of the
      right testis and epididymis and epididymal fibrosis with ductal hyperplasia on
      the left. The diagnosis was bilateral cystic rete testis, most likely secondary
      to chronic inflammation.

PMID- 16789725
TI  - Onchocercosis of an intervertebral joint capsule causing cervical vertebral
      stenotic myelopathy in a horse.
AB  - A novel case where onchocercosis was identified as a cause of cervical myelopathy
      in the horse is described. A 15-year-old Connemara mare was euthanized due to
      progressive locomotion disturbance. Postmortem examination revealed soft-tissue
      swelling in the intervertebral joint capsule of C6-7 with narrowing of the
      vertebral canal. On light microscopy, axonopathy was pronounced in the
      corresponding segment of the spinal cord. Fibrous tissue and eosinophilic
      granulomas were found in the joint capsule, together with parasites identified
      histologically as Onchocerca sp.

PMID- 16789726
TI  - Maxillary osteosarcoma in a prairie dog (Cynomys ludovicianus).
AB  - To date, few tumors have been identified in prairie dogs, with odontoma being the
      most common. Osteosarcoma has been documented in a wide range of species,
      including a number of rodents. In this case, a locally invasive maxillary
      osteosarcoma was diagnosed in a prairie dog. Gross examination revealed a pale,
      tan, lobulated, sessile maxillary mass extending ventrally into the oral cavity
      from the hard palate and the gingiva surrounding the upper right cheek teeth. The
      mass invaded the right nasal cavity and retrobulbar space causing exophthalmia.
      Microscopically, the mass consisted of densely packed spindle-shaped cells with
      occasional multinucleated giant cells. Brightly eosinophilic osteoid was
      multifocally scattered in the tumor mass. To the authors' knowledge, this is the
      first documented report of maxillary osteosarcoma in a prairie dog.

PMID- 16789727
TI  - Disseminated mycobacteriosis due to Mycobacterium avium in captive Bengal tiger
      (Panthera tigris).
AB  - A 2-year-old captive female Bengal Tiger (Panthera tigris) died after prolonged
      anorexia in the Gwangju Uchi Park Zoo, Gwangju, Republic of Korea. Necropsy
      revealed multiple nodules of varying sizes in the lung, liver, kidney, and
      spleen. Histopathologic examination revealed a typical granuloma composed of
      caseous necrotic areas surrounded by lymphocytes with a few giant cells and foamy
      macrophages. Periodic acid-Schiff stain and Gomori methenamine silver stain did
      not reveal any fungal bodies. The Ziehl-Neelsen acid-fast stain revealed few acid
      fast organisms in the lung, liver, kidney, and spleen. A polymerase chain
      reaction assay of the lung, liver, kidney, and spleen yielded a positive result
      for Mycobacterium avium subsp. avium. This is an unusual case of disseminated
      infection of a wild mammal with avian mycobacteriosis, and is believed to be most
      likely associated with the feeding of tigers with culled chickens infected with
      M. avium.

PMID- 16789729
TI  - A thienopyridazinone-based melanin-concentrating hormone receptor 1 antagonist
      with potent in vivo anorectic properties.
AB  - Melanin-concentrating hormone receptor antagonists containing thieno- and a
      benzopyridazinone cores were designed and tested as potential anorectic agents.
      These ligands showed high affinity for the receptor, potent functional activity
      in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited
      low iv clearance, long half-life, and high brain penetration. In obese rats, the
      thienopyridazinone demonstrated a dose-dependent reduction in feeding and body
      weight with doses between 1 and 10 mg kg-1.

PMID- 16789730
TI  - 3-arylimino-2-indolones are potent and selective galanin GAL3 receptor
      antagonists.
AB  - A series of 3-imino-2-indolones are the first published, high-affinity
      antagonists of the galanin GAL3 receptor. One example, 1,3-dihydro-1-phenyl-3-[[3
      (trifluoromethyl)phenyl]imino]-2H-indol-2-one (9), was shown to have high
      affinity for the human GAL3 receptor (Ki=17 nM) and to be highly selective for
      GAL3 over a broad panel of targets, including GAL1 and GAL2. Compound 9 was also
      shown to be an antagonist in a human GAL3 receptor functional assay (Kb=29 nM).

PMID- 16789731
TI  - Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53
      interaction through an integrated, virtual database screening strategy.
AB  - An integrated, virtual database screening strategy has led to 7
      [anilino(phenyl)methyl]-2-methyl-8-quinolinol (4, NSC 66811) as a novel inhibitor
      of the murine double minute 2 (MDM2)-p53 interaction. This quinolinol binds to
      MDM2 with a Ki of 120 nM and activates p53 in cancer cells with a mechanism of
      action consistent with targeting the MDM2-p53 interaction. It mimics three p53
      residues critical in the binding to MDM2 and represents a promising new class of
      non-peptide inhibitors of the MDM2-p53 interaction.

PMID- 16789732
TI  - Poly-L-glutamic acid (PGA) aided inhibitors of apoptotic protease activating
      factor 1 (Apaf-1): an antiapoptotic polymeric nanomedicine.
AB  - An antiapoptotic polymeric nanomedicine, PGA-peptoid 1, has been developed by the
      conjugation of a novel apoptotic protease activating factor 1 (Apaf-1) inhibitor
      (peptoid 1) to poly-L-glutamic acid (PGA). Full structural and biophysical
      characterization of the conjugate by different techniques has been accomplished.
      This macromolecule clearly enhances the antiapoptotic activity of peptoid 1 in
      different cell models.

PMID- 16789733
TI  - Discovery and evaluation of N-cyclopropyl- 2,4-difluoro-5-((2-(pyridin-2
      ylamino)thiazol-5- ylmethyl)amino)benzamide (BMS-605541), a selective and orally
      efficacious inhibitor of vascular endothelial growth factor receptor-2.
AB  - Substituted 3-((2-(pyridin-2-ylamino)thiazol-5-ylmethyl)amino)benzamides were
      identified as potent and selective inhibitors of vascular endothelial growth
      factor receptor-2 (VEGFR-2) kinase activity. The enzyme kinetics associated with
      the VEGFR-2 inhibition of 14 (Ki=49+/-9 nM) confirmed that the aminothiazole
      based analogues are competitive with ATP. Analogue 14 demonstrated excellent
      kinase selectivity, favorable pharmacokinetic properties in multiple species, and
      robust in vivo efficacy in human lung and colon carcinoma xenograft models.

PMID- 16789734
TI  - 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.
AB  - A structurally novel acetyl-CoA carboxylase (ACC) inhibitor is identified from
      high-throughput screening. A preliminary structure-activity relationship study
      led to the discovery of potent dual ACC1/ACC2 and ACC2 selective inhibitors
      against human recombinant ACC1 and ACC2. Selective ACC2 inhibitors exhibited
      IC50<20 nM and >1000-fold selectivity against ACC1. (S)-Enantiomer 9p exhibited
      high ACC2 activity and lowered muscle malonyl-CoA dose-dependently in acute
      rodent studies, whereas (R)-enantiomer 9o was weak and had no effect on the
      malonyl-CoA level.

PMID- 16789735
TI  - Potent benzimidazole sulfonamide protein tyrosine phosphatase 1B inhibitors
      containing the heterocyclic (S)-isothiazolidinone phosphotyrosine mimetic.
AB  - Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine
      phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide
      containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine (pTyr)
      mimetic. An X-ray cocrystal structure of inhibitor 46/PTP1B at 1.8 A resolution
      demonstrated that the benzimidazole sulfonamides form a bidentate H bond to Asp48
      as designed, although the aryl group of the sulfonamide unexpectedly interacts
      intramolecularly in a pi-stacking manner with the benzimidazole. The ortho
      substitution to the (S)-IZD on the aryl ring afforded low nanomolar enzyme
      inhibitors of PTP1B that also displayed low caco-2 permeability and cellular
      activity in an insulin receptor (IR) phosphorylation assay and an Akt
      phosphorylation assay. The design, synthesis, and SAR of this novel series of
      benzimidazole sulfonamide containing (S)-IZD inhibitors of PTP1B are presented
      herein.

PMID- 16789736
TI  - Tetraoxane antimalarials and their reaction with Fe(II).
AB  - Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4
      oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine
      susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum
      strains (IC50, IC90). Most active 13 is metabolically stable in in vitro
      metabolism studies. In vivo studies on tetraoxanes with a C(4' ') methyl group
      afforded compound 15, which cured 4/5 mice at 600 and 200 mg.kg-1.day-1, and 2/5
      mice at 50 mg.kg-1.day-1, showing no toxic effects. Tetraoxane 19 was an
      extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose
      of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO*
      radicals were detected by EPR experiments. This finding and the indication of
      Fe(IV)=O species led us to propose that RO* radicals are probably capable of
      inducing the parasite's death. Our results suggest that C radicals are possibly
      not the only lethal species derived from peroxide prodrug antimalarials, as
      currently believed.

PMID- 16789737
TI  - Synthesis, molecular characterization, and biological activity of novel synthetic
      derivatives of chromen-4-one in human cancer cells.
AB  - The synthesis and characterization of Schiff base derivatives of 3-formylchromone
      3-6 (FPA-120 to FPA-123), the minimal biologically active structural motif of soy
      isoflavone, genistein, and their copper(II) complexes 7-10 (FPA-124 to FPA-127)
      are reported here. These copper complexes possess distorted square-planar
      geometries capable of stabilizing Cu2+/Cu+ redox forms. The molecular modeling
      study revealed that the key interaction of the metal complexes was with amino
      acids in the pleckstrin homology (PH) and the kinase domain of the PKB (Akt)
      protein. Copper complex 7 significantly forms stronger charge interactions in the
      kinase domain than genistein, leading to better stabilization in the active
      pocket. In vitro evaluation of copper complexes against hormone-independent and
      metastatic breast (BT20), prostate (PC-3), and K-ras mutant (COLO 357) and K-ras
      wild-type (BxPC-3) pancreatic cancer cells revealed that 7 was the most potent
      compound which exhibited PKB (Akt protein) inhibitory activities and caused NF
      kappaB inactivation in a well-established orthotopic pancreatic tumor model using
      COLO 357 cells. An inverse relationship was observed between IC50 values of the
      anti-proliferative activities and the Cu2+/Cu+ redox couple for these compounds,
      which may provide a rapid screen for evaluating the efficacy of active
      metallodrugs affecting redox-sensitive transcription factors such as NF-kappaB
      and its upstream target, the PKB (Akt) pathway, in multiple cancers.

PMID- 16789738
TI  - Design, synthesis, and structure-activity relationships of thieno[2,3-b]pyridin-4
      one derivatives as a novel class of potent, orally active, non-peptide
      luteinizing hormone-releasing hormone receptor antagonists.
AB  - Design, synthesis, and structure-activity relationships of thieno[2,3-b]pyridin-4
      one-based non-peptide luteinizing hormone-releasing hormone (LHRH) receptor
      antagonists are described. Starting with the thienopyridin-4-one derivative 26d
      (T-98475) an optimization study was performed, which resulted in the
      identification of a highly potent and orally bioavailable LHRH receptor
      antagonist, 3-(N-benzyl-N-methylaminomethyl)-7-(2,6-difluorobenzyl)-4,7-dihydro-2
      [4-(1-hydroxy-1-cyclopropanecarboxamido)phenyl]-5-isobutyryl-4-oxothieno[2,3
      b]pyridine (33c). Compound 33c displayed subnanomolar in vitro activities for the
      human receptor and its oral administration caused effective suppression of the
      plasma LH levels in castrated male cynomolgus monkeys. Furthermore, SAR studies
      revealed that a hydroxyalkylamido moiety on the 2-phenyl ring is virtually
      equivalent to an alkylureido moiety, at least in this series of compounds.

PMID- 16789739
TI  - Toward understanding the structural basis of cyclin-dependent kinase 6 specific
      inhibition.
AB  - Cyclin-dependent kinases (CDKs) are key players in cell cycle control, and
      genetic alterations of CDKs and their regulators have been linked to a variety of
      cancers. Hence, CDKs are obvious targets for therapeutic intervention in various
      proliferative diseases, including cancer. To date, drug design efforts have
      mostly focused on CDK2 because methods for crystallization of its inhibitor
      complexes have been well established. CDK4 and CDK6, however, may be at least as
      important as enzymes for cell cycle regulation and could provide alternative
      treatment options. We describe here two complex structures of human CDK6 with a
      very specific kinase inhibitor, PD0332991, which is based on a pyrido[2,3
      d]pyrimidin-7-one scaffold, and with the less specific aminopurvalanol inhibitor.
      Analysis of the structures suggests that relatively small conformational
      differences between CDK2 and CDK6 in the hinge region are contributing to the
      inhibitor specificity by inducing changes in the inhibitor orientation that lead
      to sterical clashes in CDK2 but not CDK6. These complex structures provide
      valuable insights for the future development of CDK-specific inhibitors.

PMID- 16789740
TI  - Discovery and optimization of anthranilic acid sulfonamides as inhibitors of
      methionine aminopeptidase-2: a structural basis for the reduction of albumin
      binding.
AB  - Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As
      part of an effort to discover orally active reversible inhibitors of MetAP2, a
      series of anthranilic acid sulfonamides with micromolar affinities for human
      MetAP2 were identified using affinity selection by mass spectrometry (ASMS)
      screening. These micromolar hits were rapidly improved to nanomolar leads on the
      basis of insights from protein crystallography; however, the compounds displayed
      extensive binding to human serum albumin and had limited activity in cellular
      assays. Modifications based on structural information on the binding of lead
      compounds to both MetAP2 and domain III of albumin allowed the identification of
      compounds with significant improvements in both parameters, which showed good
      cellular activity in both proliferation and methionine processing assays.

PMID- 16789741
TI  - Photodynamic therapy agent with a built-in apoptosis sensor for evaluating its
      own therapeutic outcome in situ.
AB  - Identifying the extent of apoptosis in cells or tissues after cancer therapy in
      real time would be a powerful firsthand tool for assessing therapeutic outcome.
      We combined therapeutic and imaging functions in one agent, choosing photodynamic
      therapy (PDT) as an appropriate cancer treatment modality. This agent induces
      photodamage in irradiated cells and simultaneously identifies apoptotic cells by
      near-infrared fluorescence. This photodynamic therapy agent with a built-in
      apoptosis sensor (PDT-BIAS) contains a fluorescent photosensitizer used as an
      anticancer drug, connected to a fluorescence quencher by a caspase-3 cleavable
      peptide linker. We demonstrated that cleavage of the peptide linker by caspase-3,
      one of the executioner caspases involved in apoptosis, results in a detectable
      increase of fluorescence in solution and in cancer cells after PDT treatment. The
      apoptosis involvement and drug effectiveness were confirmed by Apoptag and cell
      viability (MTT) assays supporting the ability of PDT-BIAS to induce and image
      apoptosis in situ.

PMID- 16789742
TI  - Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors
      of phosphoinositide 3-kinase gamma.
AB  - Class I phosphoinositide 3-kinases (PI3Ks), in particular PI3Kgamma, have become
      attractive drug targets for inflammatory and autoimmune diseases. Here, we
      disclose a novel series of furan-2-ylmethylene thiazolidinediones as selective,
      ATP-competitive PI3Kgamma inhibitors. Structure-based design and X-ray
      crystallography of complexes formed by inhibitors bound to PI3Kgamma identified
      key pharmacophore features for potency and selectivity. An acidic NH group on the
      thiazolidinedione moiety and a hydroxy group on the furan-2-yl-phenyl part of the
      molecule play crucial roles in binding to PI3K and contribute to class IB PI3K
      selectivity. Compound 26 (AS-252424), a potent and selective small-molecule
      PI3Kgamma inhibitor emerging from these efforts, was further profiled in three
      different cellular PI3K assays and shown to be selective for class IB PI3K
      mediated cellular effects. Oral administration of 26 in a mouse model of acute
      peritonitis led to a significant reduction of leukocyte recruitment.

PMID- 16789743
TI  - Lipophilic pyrylium salts in the synthesis of efficient pyridinium-based cationic
      lipids, gemini surfactants, and lipophilic oligomers for gene delivery.
AB  - Several new classes of pyridinium cationic lipids were synthesized and tested as
      gene delivery agents. They were obtained through a procedure that generates
      simultaneously the heterocyclic ring and the positively charged nitrogen atom,
      using lipophilic pyrylium salts as key intermediates that react with primary
      amines, yielding pyridinium salts. The choice of the appropriately substituted
      primary amine, diamine or polyamine, allows the design of the shape of the final
      lipids, gemini surfactants, or lipophilic polycations. We report also a
      comprehensive structure-activity relationship study that identified the most
      efficient structural variables at the levels of the hydrophobic anchor, linker,
      and counterion for these classes of pyridinium cationic lipids. This study was
      also aimed at finding the best liposomal formulation for the new transfection
      agents.

PMID- 16789744
TI  - Evaluation of small-molecule modulators of the luteinizing
      hormone/choriogonadotropin and thyroid stimulating hormone receptors: structure
      activity relationships and selective binding patterns.
AB  - The substituted thieno[2,3-d]pyrimidine 3 (Org 41841), a partial agonist for the
      luteinizing hormone/choriogonadotropin receptor (LHCGR) and the closely related
      thyroid-stimulating hormone receptor (TSHR), was fundamentally altered, and the
      resulting analogues were analyzed for their potencies, efficacies, and
      specificities at LHCGR and TSHR. Chemical modification of the parent compound
      combined with prior mutagenesis of TSHR provided compelling experimental evidence
      in support of computational models of 3 binding to TSHR and LHCGR within their
      transmembrane cores. Biochemical analysis of a specific modification to the
      chemical structure of 3 provides additional evidence of a H-bond between the
      ligand and a glutamate residue in transmembrane helix 3, which is conserved in
      both receptors. Several key interactions were surveyed to determine their
      respective biochemical roles in terms of both van der Waals dimensions and
      hydrogen bond capacity and the respective relationship to biological activity.

PMID- 16789745
TI  - Synthesis and anticancer activity of brefeldin A ester derivatives.
AB  - Ester derivatives of brefeldin A (BFA) were synthesized to determine which of its
      two hydroxyl groups could be modified while still maintaining biological
      activity. The compounds were tested for antiproliferative activity in the
      National Cancer Institute's 60 cancer cell line screen. Monoderivatization at the
      C4 and C7 alcohols was tolerated, yielding biologically active compounds, whereas
      the analogues derivatized at both positions were the least active in the series.
      Molecular modeling of the analogues revealed that both the C4 and C7 derivatives
      were well tolerated at the interface between ARF1 and its guanine nucleotide
      exchange factor ARNO. The Golgi-disruptive properties of the analogues were
      determined using fluorescence imaging assays. The BFA ester conjugates
      synthesized in this study were cytotoxic to cancer cells, and we have shown that
      the disruption of the Golgi complex is not necessary for cytotoxicity. The
      brefeldin A ester derivatives are potential anticancer agents.

PMID- 16789747
TI  - 4-amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as new potent and selective
      human A3 adenosine receptor antagonists. synthesis, pharmacological evaluation,
      and ligand-receptor modeling studies.
AB  - A structural investigation on some 4-amido-2-phenyl-1,2-dihydro-1,2,4
      triazolo[4,3-a]quinoxalin-1-one derivatives, designed as human A3 adenosine
      receptor (hA3 AR) antagonists, is described. In the new derivatives, some acyl
      residues with different steric bulk were introduced on the 4-amino group, and
      their combination with the 4-methoxy group on the 2-phenyl moiety, and/or the 6
      nitro/6-amino substituent on the fused benzo ring, was also evaluated. Most of
      the new derivatives were potent and selective hA3 AR antagonists. SAR analysis
      showed that hindering and lipophilic acyl moieties not only are well tolerated
      but even ameliorate the hA3 affinity. Interestingly, the 4-methoxy substituent on
      the appended 2-phenyl moiety, as well as the 6-amino group, always exerted a
      positive effect, shifting the affinity toward the hA3 receptor subtype. In
      contrast, the 6-nitro substituent exerted a variable effect. An intensive
      molecular modeling investigation was performed to rationalize the experimental
      SAR findings.

PMID- 16789746
TI  - Synthesis and biological evaluation of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-5
      aryl thiophenes as a new class of potent antitubulin agents.
AB  - A new series of compounds in which the 2-amino-5-chlorophenyl ring of phenstatin
      analogue 7 was replaced with a 2-amino-5-aryl thiophene was synthesized and
      evaluated for antiproliferative activity and for inhibition of tubulin
      polymerization and colchicine binding to tubulin. 2-Amino-3-(3',4',5'
      trimethoxybenzoyl)-5-phenyl thiophene (9f) as well as the p-fluoro-, p-methyl-,
      and p-methoxyphenyl substituted analogues (9i, j, and l, respectively) displayed
      high antiproliferative activities with IC50 values from 2.5 to 6.5 nM against the
      L1210 and K562 cell lines. Compounds 9i and j were more active than
      combretastatin A-4 as inhibitors of tubulin polymerization. Molecular docking
      simulations to the colchicine site of tubulin were performed to determine the
      possible binding mode of 9i. The results obtained demonstrated that
      antiproliferative activity correlated well with the inhibition of tubulin
      polymerization and the lengthening of the G2/M phase of the cell cycle. Moreover,
      a good correlation was found between these inhibitory effects and the induction
      of apoptosis in cells treated with the compounds.

PMID- 16789748
TI  - Exploration of orally available calpain inhibitors 2: peptidyl hemiacetal
      derivatives.
AB  - We previously reported a potent calpain inhibitor 1 (SJA6017, N-(4-fluorophenyl)
      l-valyl-l-leucinal), which displayed relatively low oral bioavailability (BA).
      Replacing the metabolically labile aldehyde moiety of 1with more chemically
      stable warheads, such as a cyclic hemiacetal, hydrazone, and alpha-ketoamide,
      provided the inhibitors with improved in vitro metabolic stability. Cyclic
      hemiacetal 2 was the most stable of these compounds. The optimization of 2 led to
      hemiacetal 8 (SNJ-1715) which exhibited high potency, good aqueous solubility,
      excellent oral BA, and prolonged plasma half-life in rats. Furthermore, 8 showed
      neuroprotective efficacy via oral administration in a rat retinal ischemia model.

PMID- 16789749
TI  - Inhibition of lysosomal cysteine proteases by a series of Au(I) complexes: a
      detailed mechanistic investigation.
AB  - Complexes of gold(I) have long been used to treat rheumatoid arthritis although
      the precise biological targets of gold are not well understood. One intriguing
      therapeutic target of Au(I) is the cathepsin family of lysosomal cysteine
      proteases. Here, we present the inhibition of cathepsin B by a known Au(I)-based
      drug and a series of derivatives. The complexes investigated were reversible,
      competitive inhibitors with IC50 values ranging from 0.3 to 250 microM, depending
      on the substituents around the Au(I).

PMID- 16789750
TI  - 2-[(4-phenylpiperazin-1-yl)methyl]imidazo(di)azines as selective D4-ligands.
      Induction of penile erection by 2-[4-(2-methoxyphenyl)piperazin-1
      ylmethyl]imidazo[1,2-a]pyridine (PIP3EA), a potent and selective D4 partial
      agonist.
AB  - A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza
      analogues were prepared and screened at selected dopamine, serotonin, and
      adrenergic receptor subtypes. 2-Substituted imidazopyridines and pyridazines
      presented high affinities and selectivities for D4 dopamine receptors. Whereas
      functional experiments indicated neutral antagonists or weak partial agonist
      effects for most of the target compounds, the 2-methoxyphenyl substituted 2
      piperazinylmethylimidazopyridine 3c (PIP3EA) displayed substantial agonist
      efficacy in mitogenesis experiments and GTPgammaS binding tests, resulting in
      EC50 values of 3.0 (46%) and 4.5 nM (57%), respectively. Our D4 agonist 3c
      induced penile erection in vivo when administered to rats. This effect was
      inhibited by L-745,870 a D4 selective antagonist, confirming the mechanistic
      pathway.

PMID- 16789751
TI  - Parallel artificial membrane permeability assay: a new membrane for the fast
      prediction of passive human skin permeability.
AB  - This work was devoted to the search for new artificial membranes allowing a rapid
      evaluation of passive human skin permeation of compounds with a parallel
      artificial membrane permeability assay (PAMPA). Effective permeability
      coefficients (Pe) determined for a set of compounds using the PAMPA technique
      with isopropyl myristate (IPM) and silicone oil, alone or in mixture, were
      compared to the corresponding human skin permeability coefficient values (Kp). A
      good correlation between Pe and Kp was found for compounds tested through a
      membrane consisting of 70% silicone and 30% IPM. Moreover, positive correlation
      between the membrane retention of compounds and stratum corneum/water partition
      coefficients (PSC) was established. These results showed that this new artificial
      membrane, defined as PAMPA-skin, is able to mimic the main barrier properties of
      human stratum corneum and can be used for the fast prediction of passive human
      skin permeability coefficients.

PMID- 16789752
TI  - Activation of murine RNase L by isopolar 2'-phosphonate analogues of 2',5'
      oligoadenylates.
AB  - To determine the influence of methylene group insertion in the internucleotide
      linkage on the binding process of 2',5'-oligoadenylates to RNase L, a series of
      2'-phosphonate-modified trimers and tetramers were synthesized from appropriate
      monomeric units and evaluated for their ability to bind to murine RNase L.
      Tetramers pAAXA modified by ribo-, arabino-, or xylo-2'-phosphonate unit X in the
      third position were capable of binding to RNase L in nanomolar concentrations.
      The replacement of the first residue (pXAAA), or both the first and the third
      residues (pXAXA), was also tolerated by the enzyme. In contrast, in all cases,
      the replacement of the second residue (pAXAA) resulted in the significant
      decrease of binding ability. Additionally, no more than two phosphonate
      modifications in the tetramer were allowed to retain the binding affinity to the
      enzyme. Although all three tetramers pAAXA were found to be potent enzyme
      binders, only tetramers modified by ribo- and xylo-2'-phosphonate unit X
      activated the RNase L-catalyzed cleavage of the RNA substrate. Surprisingly,
      tetramer pAAXA, modified by arabino-2'-phosphonate unit X, did not activate the
      enzyme and can be considered a potent antagonist. In comparison with their
      natural counterpart, the phosphonate analogues of the pA4 exhibit superior
      resistance toward nucleases present in the murine spleen homogenate.

PMID- 16789753
TI  - Antitumor agents. 250. Design and synthesis of new curcumin analogues as
      potential anti-prostate cancer agents.
AB  - In a continuing study of curcumin analogues as potential drug candidates to treat
      prostate cancer at both androgen-dependent and androgen-refractory stages, we
      designed and synthesized over 40 new analogues classified into four series:
      monophenyl analogues (series A), heterocycle-containing analogues (series B),
      analogues bearing various substituents on the phenyl rings (series C), and
      analogues with various linkers (series D). These new compounds were tested for
      cytotoxicity against two human prostate cancer cell lines, androgen-dependent
      LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated
      in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten
      compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells, seven
      only against LNCaP, and one solely against PC-3. This study established an
      advanced structure-activity relationship (SAR), and these correlations will guide
      the further design of new curcumin analogues with better anti-prostate cancer
      activity.

PMID- 16789754
TI  - Structural studies on bioactive compounds. 40.(1) Synthesis and biological
      properties of fluoro-, methoxyl-, and amino-substituted 3-phenyl-4H-1-benzopyran
      4-ones and a comparison of their antitumor activities with the activities of
      related 2-phenylbenzothiazoles.
AB  - A new series of fluoro-, methoxyl-, and amino-substituted isoflavones have been
      synthesized as potential antitumor agents based on structural similarities to
      known flavones and isoflavones (quercetin and genistein respectively) and
      antitumor 2-phenylbenzothiazoles. Target compounds were synthesized using
      palladium-catalyzed coupling methodologies to construct the central aryl carbon
      carbon single bond. The new isoflavone derivatives were tested for in vitro
      activity in human breast (MDA-MB-468 and MCF-7) and colon (HT29 and HCT-116)
      cancer cell lines. Low micromolar GI50 values were obtained in a number of cases,
      with the MDA-MB-468 cell line being the most sensitive overall. Notably,
      significant potentiation of growth inhibitory activity (GI50<1 microM for 12d,
      12f, 12h, 12k, 12l, 12o but not the methylene-bridged derivative 12i) was
      observed when MDA-MB-468 cells were co-incubated with TBDD, a powerful inducer of
      cytochrome P450 (CYP)-1A1 activity, suggesting that isoflavone derivatives can
      act as substrates for CYP1A1 bioactivation.

PMID- 16789755
TI  - S-alkylated homocysteine derivatives: new inhibitors of human betaine
      homocysteine S-methyltransferase.
AB  - A series of S-alkylated derivatives of homocysteine were synthesized and
      characterized as inhibitors of human recombinant betaine-homocysteine S
      methyltransferase (BHMT). Some of these compounds inhibit BHMT with IC50 values
      in the nanomolar range. BHMT is very sensitive to the structure of substituents
      on the sulfur atom of homocysteine. The S-carboxybutyl and S-carboxypentyl
      derivatives make the most potent inhibitors, and an additional sulfur atom in the
      alkyl chain is well tolerated. The respective (R,S)-5-(3-amino-3-carboxy
      propylsulfanyl)-pentanoic, (R,S)-6-(3-amino-3-carboxy-propylsulfanyl)-hexanoic,
      and (R,S)-2-amino-4-(2-carboxymethylsulfanyl-ethylsulfanyl)-butyric acids are
      very potent inhibitors and are the strongest ever reported. We determined that
      (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid displays competitive
      inhibition with respect to betaine binding with a Kappi of 12 nM. Some of these
      compounds are currently being tested in mice to study the influence of BHMT on
      the metabolism of sulfur amino acids in vivo.

PMID- 16789757
TI  - Binding mode prediction of strand transfer HIV-1 integrase inhibitors using Tn5
      transposase as a plausible surrogate model for HIV-1 integrase.
AB  - The crystal structure of Tn5 transposase-DNA complex was used in docking
      experiments to predict binding modes of HIV-1 integrase strand transfer
      inhibitors (INSTIs). In fact, the identification of HIV-1 integrase inhibitors
      from an in vitro screen using Tn5 transposase as the target has been recently
      reported. Our results suggest the utility of this protein as a useful surrogate
      model for IN and also for in silico screening, in the search for new potential
      INSTIs.

PMID- 16789756
TI  - New 2',6'-dimethyl-L-tyrosine (Dmt) opioid peptidomimetics based on the Aba-Gly
      scaffold. Development of unique mu-opioid receptor ligands.
AB  - The Aba-Gly scaffold, incorporated into Dmt-Tic ligands (H-Dmt-Tic-Gly-NH-CH2-Ph,
      H-Dmt-Tic-Gly-NH-Ph, H-Dmt-Tic-NH-CH2-Bid), exhibited mixed micro/delta or delta
      opioid receptor activities with micro agonism. Substitution of Tic by Aba-Gly
      coupled to -NH-CH2-Ph (1), -NH-Ph (2), or -Bid (Bid=1H-benzimidazole-2-yl) (3)
      shifted affinity (Ki(micro)=0.46, 1.48, and 19.9 nM, respectively), selectivity,
      and bioactivity to micro-opioid receptors. These compounds represent templates
      for a new class of lead opioid agonists that are easily synthesized and suitable
      for therapeutic pain relief.

PMID- 16789759
TI  - A closed-loop identification protocol for nonlinear dynamical systems.
AB  - A previous work introduced an optimal identification (OI) technique for reliably
      extracting model parameters of biochemical reaction systems from tailored
      laboratory experiments. The notion of optimality enters through seeking an
      external control in the laboratory producing data that leads to minimum
      uncertainties in the identified parameter distributions. A number of algorithmic
      and operational improvements are introduced in this paper to OI, aiming to build
      a more practical and efficient closed-loop identification protocol/procedure
      (CLIP) for nonlinear dynamical systems. The improvements in CLIP include (a)
      inversion cost function modification to preferably search for the upper and lower
      boundaries of the parameter distributions consistent with the observed data, (b)
      dynamic search range updating of the unknown parameters to better exploit the
      information from the prior iterative experiments, (c) replacing the control
      genetic algorithm by the simplex method to enable better balance between
      operational cost and inversion quality, and (d) utilizing virtual sensitivity
      optimization techniques to further reduce the laboratory costs. The workings of
      CLIP utilizing these new algorithms are illustrated in indentifying a simulated
      tRNA proofreading model, and the results demonstrate enhanced performance of CLIP
      in terms of algorithmic reliability and efficiency.

PMID- 16789758
TI  - Wavelength dependent photofragmentation patterns of tris(2,2,6,6-tetramethyl-3,5
      heptanedionato)Ln (III) (Ln = Eu, Tb, Gd) in a molecular beam.
AB  - Laser photoionization and ligand photodissociation in Ln(thd)(3) (Ln = Eu, Tb,
      Gd; thd = 2,2,6,6-tetramethyl-3,5-heptanedionato) are studied in a molecular beam
      via time-of-flight mass spectrometry. The fragmentation patterns are strongly
      wavelength dependent. With 355 nm excitation, the mass spectrum is dominated by
      Ln(2+), Ln(+), and LnO(+) fragments. The bare Ln ions are believed to arise from
      photoionization of neutral Ln atoms. The Ln atoms, in turn, are produced from the
      Ln(thd)(3) complex in a sequence of Ln reductions (through ligand-to-metal charge
      transfer transitions), with each reduction being accompanied by the dissociation
      of a neutral ligand radical. In contrast, under visible-light (410-450 nm)
      excitation, a significant Ln(thd)(n)(+) signal is observed (where n = 2,3 for Ln
      = Tb,Gd and n = 1-3 for Ln = Eu). Thus, with visible excitation, photoionization
      of Ln(thd)(n) competes effectively with the Ln-reduction/ligand-dissociation
      sequence that leads to the dominant bare Ln-ion signal seen with 355 nm
      excitation. The fact that monoligated Ln(thd)(+) is observed only for Ln = Eu is
      interpreted in terms of the relative accessibility of an excited ligand-to-metal
      charge-transfer state from the ground electronic state of neutral Ln(thd).

PMID- 16789760
TI  - Femtosecond laser ionization of organic amines with very low ionization
      potentials: relatively small suppressed ionization features.
AB  - We examined the femtosecond nonresonant ionization of organic amines with
      vertical ionization potentials as low as 5.95 eV. The quantitative evaluation of
      suppressed ionization relative to the single active electron approximation model
      was done by comparing the saturation intensity, I(sat), in experiments and
      theory. ADK theory was found to be useful in predicting the ionization yield in
      the I(sat) scale within a factor of 2, even for molecules with very low
      ionization potentials. The degree of suppression was, however, smaller than that
      of benzene. The localization of electrons on the nitrogen atom was found to
      affect the ionization behavior under the strong laser field. The delocalized pi
      electrons in benzene could not follow the laser field adiabatically, while those
      in localized molecular orbitals could. In addition, the growth of a tunneling
      barrier due to the screening effect in amines may be relatively smaller than that
      in benzene.

PMID- 16789761
TI  - Photochemistry via photoelectron spectroscopy: N-substituted phthalimides.
AB  - The electronic structures of several N-substituted phthalimides have been
      investigated by UV photoelectron spectroscopy and outer valence Greens function
      calculations. Some spectra reveal the presence of photofragmentation and
      photoelimination processes related to the decay of the aminium radical cation. We
      compared the fragmentation mechanisms in the gas phase and in the solution.

PMID- 16789762
TI  - Cluster phase chemistry: gas-phase reactions of anionic sodium salts of
      dicarboxylic acid clusters with water molecules.
AB  - A homologous series of anionic gas-phase clusters of dicarboxylic acids (oxalic
      acid, malonic acid, succinic acid, glutaric acid, and adipic acid) generated via
      electrospray ionization (ESI) are investigated using collision-induced
      dissociation (CID). Sodiated clusters with the composition
      (Na(+))(2)(n+1)(dicarboxylate(2-)(n+1) for singly charged anionic clusters, where
      n = 1-4, are observed as major gas-phase species. Isolation of the clusters
      followed by CID results mainly in sequential loss of disodium dicarboxylate
      moieties for the clusters of succinic acid, glutaric acid, and adipic acid (C4
      C6). However, all oxalate (C2) and malonate (C3) clusters and dimers (n = 1) of
      succinate (C4) and glutarate (C5) exhibit more complex chemistry initiated by
      collision of the activated cluster with water molecules. For example, with water
      addition, malonate clusters dissociate to yield sodium acetate, carbon dioxide,
      and sodium hydroxide. More generally, water molecules serve as proton donors for
      reacting dicarboxylate anions in the cluster and introduce energetically
      favorable dissociation pathways not otherwise available. Density functional
      theory (DFT) calculations of the binding energy of the cluster correlate well
      with the cluster phase reactions of oxalate and malonate clusters. Clusters of
      larger dicarboxylate ions (C4-C6) are more weakly bound, facilitating the
      sequential loss of disodium dicarboxylate moieties. The more strongly bound small
      dicarboxylate anions (oxalate and malonate) preferentially react with water
      molecules rather than dissociate to lose disodium dicarboxylate monomers when
      collisionally activated. Implications of these results for the atmospheric
      aerosol chemistry of dicarboxylic acids are discussed.

PMID- 16789764
TI  - New theoretical and experimental infrared results on formaldehyde in solution.
AB  - An extension of our combined procedure to determine a complete quartic force
      field and to resolve a vibrational problem thanks to a variational treatment is
      proposed for quantitative calculations of vibrational spectra in solution.
      Energies and gradients are obtained through a polarizable continuum model (PCM),
      the so-called self-consistent isodensity (SCI)-PCM. We present in this paper new
      experimental results dealing with formaldehyde in solution in cyclohexane,
      chloroform, THF, acetonitrile, DMSO and water; the obtained vibrational spectra
      are then compared with CCSD(T)/cc-pVQZ calculations. In addition, density
      functional theory (DFT) calculations have been carried out with the aim of both
      anticipating and positioning these approaches for larger sized molecules.

PMID- 16789763
TI  - Relationship between NMR shielding and heme binding strength for a series of 7
      substituted quinolines.
AB  - Chemical shielding tensors are calculated for the carbons in a series of 4
      aminoquinolines with different substituents at the 7-position. The sigma(11)
      component is used as a measure of the relative pi-electron density at each
      carbon. By comparing the pi-electron density at each carbon with the log K of
      binding to heme (Kaschula et al. J. Med. Chem. 2002, 45, 3531), the drug-heme
      association is found to increase with increasing pi-electron density at the
      carbons meta to the substituent and with decreasing pi-electron density at the
      carbons ortho and para to the substituent. The greatest change in pi-electron
      density is at the ortho carbons, and log K increases with a decrease in pi
      electron density on the ring containing the substituent, which corresponds to an
      increase in the pi-dipole between the two rings. An examination of the solution
      structures of the pi-pi complexes formed by amodiaquine and quinine with heme
      (Leed et al. Biochemistry 2002, 41, 10245. de Dios et al. Inorg. Chem. 2004, 43,
      8078) shows that the pi-dipoles in each drug and in the porphyrin ring of heme
      may be paired. The chloro-substituted compound has an association constant that
      is an order of magnitude higher than the other compounds in the series, but the
      pi-electron density at the ring containing the substituent is not correspondingly
      low. This lack of correlation indicates that the Cl-substituted compound may be
      binding to heme in a manner that differs from the other compounds in the series.

PMID- 16789765
TI  - Low-temperature photoelectron spectroscopy of aliphatic dicarboxylate monoanions,
      HO2C(CH2(nCO2- (n = 1-10): hydrogen bond induced cyclization and strain energies.
AB  - Photoelectron spectra of singly charged dicarboxylate anions
      HO(2)C(CH(2))(n)CO(2)(-) (n = 1-10) are obtained at two different temperatures
      (300 and 70 K) at 193 nm. The electron binding energies of these species are
      observed to be much higher than the singly charged monocarboxylate anions,
      suggesting that the singly charged dicarboxylate anions are cyclic due to strong
      intramolecular hydrogen bonding between the terminal -CO(2)H and -CO(2)(-)
      groups. The measured electron binding energies are observed to depend on the
      chain length, reflecting the different -CO(2)H...(-)O(2)C- hydrogen bonding
      strength as a result of strain in the cyclic conformation. A minimum binding
      energy is found at n = 5, indicating that its intramolecular hydrogen bond is the
      weakest. At 70 K, all spectra are blue shifted relative to the room-temperature
      spectra with the maximum binding energy shift occurring at n = 5. These
      observations suggest that the cyclic conformation of HO(2)C(CH(2))(5)CO(2)(-) (a
      ten-membered ring) is the most strained among the 10 anions. The present study
      shows that the -CO(2)H...(-)O(2)C- hydrogen bonding strength is different among
      the 10 anions and it is very sensitive to the strain in the cyclic conformations.

PMID- 16789766
TI  - Group 4 transition metal-benzene adducts: carbon ring deformation upon
      complexation.
AB  - Benzene is reacted with titanium, zirconium, and hafnium metal atoms, which are
      produced by laser-ablation. The M(C(6)H(6)), M(C(6)H(6))(2), and
      M(2)(C(6)H(6))(3) complexes are formed, isolated in solid argon, and identified
      by infrared spectroscopy using isotopic substitution of the benzene precursor.
      Density functional theory (DFT) calculations are used to confirm molecular
      assignments. Based on computed energies and the observed vibrational spectra and
      isotopic shifts, electronic ground states and geometries are predicted. Observed
      splitting of formerly degenerate modes provides the first experimental evidence
      for deformation of the planar carbon skeleton of benzene upon complexation with
      early transition metal atoms.

PMID- 16789767
TI  - Structure and matrix isolation infrared spectrum of formyl fluoride dimer: blue
      shift of the C-H stretching frequency.
AB  - Infrared spectroscopy (IR) of formyl fluoride (HCOF) dimer is studied in low
      temperature argon and krypton matrixes. New IR absorptions, ca. 17 cm(-1) blue
      shifted from the monomer C-H stretching fundamental, are assigned to the HCOF
      dimer. The MP2/6-311++G calculations were utilized to define structures and
      harmonic frequencies of various HCOF dimers. Among the four optimized structures,
      the dimer having two C-H...O hydrogen bonds possesses strongest intermolecular
      bonding. The calculated harmonic frequencies of this dimer structure are shifted
      from the monomer similarly as observed in the experiment. Thus, we suggest that
      the experimentally observed blue shifted C-H bands belong to the dimer with two C
      H...O hydrogen bonds. This observation includes the HCOF dimer to the class of
      hydrogen bonded complexes showing blue shift in their vibrational energies.

PMID- 16789768
TI  - Photoinduced Rydberg ionization spectroscopy of phenylacetylene: vibrational
      assignments of the C state of the cation.
AB  - The photoinduced Rydberg ionization spectrum of the third excited electronic
      state of phenylacetylene cation was recorded via the origin of the cation ground
      electronic state. The origin of this state is 17 834 cm(-1) above the ground
      state of the cation, and the spectrum shows well-resolved vibrational features to
      the energy of 2200 cm(-1) above this. An assignment of the vibrational structure
      was made by comparison to calculated frequencies and Franck-Condon factors. From
      the assignments, and electronic structure considerations, the electronic symmetry
      of the C state is established to be (2)B(1).

PMID- 16789769
TI  - Experimental and theoretical study of the electronic spectrum of the methylene
      amidogen radical (H2CN): verification of the 2A1 <-- 2B2 assignment.
AB  - A collaborative experimental and theoretical study of the electronic spectrum and
      excited-state photochemistry of H(2)CN has been carried out. The absorption
      spectrum, in the range of 287-278 nm, was measured through cavity ring-down
      spectroscopy. The radical was prepared by 193 nm photolysis of monomeric
      formaldoxime vapor. Two diffuse features were observed in the 34800-35800 cm(-1)
      spectral range, along with the A-X (1,0) band of the OH cofragment. The broad
      features were assigned through high-level ab initio calculations as vibronic
      transitions to the ground and 2b(1) (umbrella mode) levels of the second excited
      B (2)A(1) state from the ground X (2)B(2) state of H(2)CN. Rotational constants
      for the lower and upper levels of these transitions were computed from the
      expectation values of the moments of inertia tensor, using the appropriate
      vibrational wave functions. Experimental and simulated rotational profiles of
      these bands agree extremely well with each other for an assumed type-B electric
      dipole-allowed (2)A(1) <-- (2)B(2) transition appropriate to this transition. The
      former assignment to the dipole-forbidden (2)B(1) <-- (2)B(2) transition can be
      ruled out by these results. A theoretical investigation of the dissociation
      pathways for electronically excited H(2)CN is also presented. The upper states of
      the observed bands cannot dissociate directly but rather decay through internal
      conversion and subsequent dissociation to H + HCN fragments; higher b(1) levels
      are above the excited-state dissociation limit.

PMID- 16789770
TI  - Caging effects on the ground and excited states of 2,2'-bipyridine-3,3'-diol
      embedded in cyclodextrins.
AB  - The 2,2'-bipyridine-3,3'-diol (BP(OH)(2)) molecule shows unique spectroscopic
      features in water that may position it as a new biological probe. In an attempt
      to mimic biological environments, we explore in this paper the caging effects of
      cyclodextrins on the steady state spectra of BP(OH)(2). The caging effects of
      gamma-, beta-, and 2,6-di-O-methyl-beta-cyclodextrins (CDs) on the ground and
      excited state properties of BP(OH)(2) in aqueous solutions are investigated by
      steady state absorption and fluorescence spectroscopy, and by ab initio
      calculations. The stoichiometry of the three complexes was found to be 1:1 and
      the binding constants were estimated from the absorption and fluorescence
      spectra. In the case of gamma-CD, the large cavity size supports only small
      binding, whereas such binding increases in the cases of the smaller cavity sizes
      of beta-CD and 2,6-di-O-methyl-beta-CD. Maximum binding was measured in the case
      of 2,6-di-O-methyl-beta-CD due to the increased hydrophobicity of the host
      cavity. The unique absorption features of BP(OH)(2) in water show a dramatic
      decrease in intensity due to caging effects. The decrease in intensity correlates
      very well with the extent of binding and hydrophobicity of the host molecules.
      Similar results were also obtained from the fluorescence spectra. The calculated
      structure of the BP(OH)(2):beta-CD complex predicts that the inclusion of
      BP(OH)(2) is nearly axial and centered inside the beta-CD cavity. The BP(OH)(2)
      molecule maintains its dienol moiety in the complex with no possible hydrogen
      bonding with the host interior H-atoms. The results are discussed in light of the
      possible use of BP(OH)(2) as a water sensor in biological systems.

PMID- 16789771
TI  - Phenol production in benzene/air plasmas at atmospheric pressure. Role of radical
      and ionic routes.
AB  - Benzene can be efficiently converted into phenol when it is treated by either
      corona or dielectric barrier discharge (DBD) plasmas operating at atmospheric
      pressure in air or mixtures of N(2) and O(2). Phenol produced by corona discharge
      in an atmospheric pressure chemical ionization source (APCI) has been detected as
      the corresponding radical cation C(6)H(5)OH(+*) at m/z 94 by an ion trap mass
      spectrometer. On the other hand, phenol has been observed also as neutral product
      by gas chromatography-mass spectrometry analysis (GC-MS) after treatment in a DBD
      plasma. Experiments aimed at shading light on the elementary processes
      responsible for benzene oxidation were carried out (i) by changing the
      composition of the gas in the corona discharge source; (ii) by using isotopically
      labeled reagents; and (iii) by investigating some relevant ion-molecule reactions
      (i.e. C(6)H(6)(+*) + O(2), C(6)H(5)(+) + O(2)) via selected guided ion beam
      measurements and with the help of ab initio calculations. The results of our
      approach show that ionic mechanisms do not play a significant role in phenol
      production, which can be better explained by radical reactions resulting in
      oxygen addition to the benzene ring followed by 1,2 H transfer.

PMID- 16789772
TI  - Study of benzylperoxy radical using laser photolysis: ultraviolet spectrum, self
      reaction, and reaction with HO2 kinetics.
AB  - The ultraviolet absorption spectrum of benzylperoxy radical and the kinetics of
      the reactions 2C(6)H(5)CH(2)O(2) --> products (I) and C(6)H(5)CH(2)O(2) + HO(2) -
      > products (II) are studied. Experiments are carried out using the laser
      photolysis technique with time-resolved UV-visible absorption spectroscopy over
      the temperature range 298-353 K and the pressure range 50-200 Torr. The UV
      spectrum is determined relative to the known cross section of the ethylperoxy
      radical C(2)H(5)O(2) at 250 nm. Using factor analysis, the spectrum obtained is
      refined and the concentrations of the main absorbing species are extracted. The
      kinetic parameters are determined by analyzing and simulating the temporal
      profiles of the species concentrations and the experimental optical densities in
      the spectral region 220-280 nm. These are obtained using the recent UV spectra of
      the absorbing species existing in our mechanism. The Arrhenius expressions for
      reactions I and II are (cm(3).molecule(-1).s(-1)) k(I) = 2.50 x 10(
      14)e(1562/)(T) and k(II) = 5.70 x 10(-14)e(1649/)(T). Our results are discussed
      and compared to literature data.

PMID- 16789773
TI  - A theoretical study of the reaction of O(3P) with isobutene.
AB  - The reaction of O((3)P) with isobutene ((CH(3))(2)C=CH(2)) is investigated using
      the unrestricted second-order Moller-Plesset perturbation (UMP2) and complete
      basis set CBS-4M level methods. The minimum energy crossing point (MECP) between
      the singlet and triplet potential energy surfaces is located using the Newton
      Lagrange method, and it is shown that the MECP plays a key role. The
      calculational results indicate that the site selectivity of the addition of
      O((3)P) to either carbon atom of the double bond of isobutene is weak, and the
      major product channels are CH(2)C(O)CH(3) + CH(3,) cis-/trans-CH(3)CHCHO + CH(3),
      (CH(3))(2)CCO + H(2), and CH(3)C(CH(2))(2) + OH, among which (CH(3))(2)CCO + H(2)
      is predicted to be the energetically most favorable one. The complex multichannel
      reaction mechanisms are revealed, and the observations in several recent
      experiments could be rationalized on the basis of the present calculations. The
      formation mechanisms of butenols are also discussed.

PMID- 16789774
TI  - Activation energy for the disproportionation of HBrO2 and estimated heats of
      formation of HBrO2 and BrO2.
AB  - The kinetics of the reaction HBrO(2) + HBrO(2) --> HOBr + BrO(3)(-) + H(+) is
      investigated in aqueous HClO(4) (0.04-0.9 M) and H(2)SO(4) (0.3-0.9 M) media and
      at temperatures in the range 15-38 degrees C. The reaction is found to be cleanly
      second order in [HBrO(2)], with the experimental rate constant having the form
      k(exp) = k + k'[H(+)]. The half-life of the reaction is on the order of a few
      tenths of a second in the range 0.01 M < [HBrO(2)](0) < 0.02 M. The detailed
      mechanism of this reaction is discussed. The activation parameters for kare found
      to be E(double dagger) = 19.0 +/- 0.9 kJ/mol and DeltaS(double dagger) = -132 +/-
      3 J/(K mol) in HClO(4), and E(double dagger) = 23.0 +/- 0.5 kJ/mol and
      DeltaS(double dagger) = -119 +/- 1 J/(K mol) in H(2)SO(4). The activation
      parameters for k' are found to be E(double dagger) = 25.8 +/- 0.5 kJ/mol and
      DeltaS(double dagger) = -106 +/- 1 J/(K mol) in HClO(4), and E(double dagger) =
      18 +/- 3 kJ/mol and DeltaS(double dagger) = -130 +/- 11 J/(K mol) in H(2)SO(4).
      The values Delta(f)H(29)(8)(0)[BrO(2)(aq)] = 157 kJ/mol and
      Delta(f)H(29)(8)(0)[HBrO(2)(aq)] = -33 kJ/mol are estimated using a trend
      analysis (bond strengths) based on the assumption
      Delta(f)H(29)(8)(0)[HBrO(2)(aq)] lies between Delta(f)H(29)(8)(0)[HOBr(aq)] and
      Delta(f)H(29)(8)(0)[HBrO(3)(aq)] as Delta(f)H(29)(8)(0)[HClO(2)(aq)] lies between
      Delta(f)H(29)(8)(0)[HOCl(aq)] and Delta(f)H(29)(8)(0)[HClO(3)(aq)]. The estimated
      value of Delta(f)H(29)(8)(0)[BrO(2)(aq)] agrees well with calculated gas-phase
      values, but the estimated value of Delta(f)H(29)(8)(0)[HBrO(2)(aq)], as well as
      the tabulated value of Delta(f)H(29)(8)(0)[HClO(2)(aq)], is in substantial
      disagreement with calculated gas-phase values. Values of Delta(r)H(0) are
      estimated for various reactions involving BrO(2) or HBrO(2).

PMID- 16789775
TI  - Kinetic study of the reaction Ca+ + N2O from 188 to 1207 K.
AB  - Ion-molecule reactions involving metallic species play a central role in the
      chemistry of planetary ionospheres and in many combustion processes. The kinetics
      of the Ca(+) + N(2)O --> CaO(+) + N(2) reaction was studied by the pulsed
      multiphoton dissociation at 193 nm of organo-calcium vapor in the presence of
      N(2)O, followed by time-resolved laser-induced fluorescence spectroscopy of Ca(+)
      at 393.37 nm (4(2)P(3/2) <-- 4(2)S(1/2)). This yielded k(188-1207 K) = 5.45 x 10(
      11) (T/300 K)(0.53) exp(282 K/T) cm(3) molecule(-1) s(-1), with an estimated
      accuracy of +/-13% (188-600 K) and +/-27% (600-1207 K). The temperature
      dependence of this barrierless reaction, with a minimum in the rate coefficient
      between 400 and 600 K, appears to be explained by the role of N(2)O vibrational
      excitation. This is examined using a classical trajectory treatment on a
      potential energy surface calculated at the B3LYP/6-311+g(2d,p) level of theory.

PMID- 16789776
TI  - On the variety of traveling fronts in one-variable multistable reaction-diffusion
      systems.
AB  - The still-open problem of the variety of asymptotic solutions to one-variable,
      one-dimensional infinite multistable reaction-diffusion systems is solved. We
      show that in such systems, besides monotonic traveling fronts, nonmonotonic
      traveling fronts can exist for appropriate initial conditions. The dependence of
      numbers of various types of traveling fronts on the number of stable stationary
      states also is given. Examples of traveling fronts for the chemical model
      describing two enzymatic (catalytic) reactions inhibited by an excess of their
      reactant is presented.

PMID- 16789777
TI  - On modeling the pressure-dependent photoisomerization of trans-stilbene by
      including slow intramolecular vibrational energy redistribution.
AB  - Experimental data for the photoisomerization of trans-stilbene (S(1)) in thermal
      bath gases at pressures up to 20 bar obtained previously by Meyer, Schroeder, and
      Troe (J. Phys. Chem. A 1999, 103, 10528-10539) are modeled by using a full
      collisional-reaction master equation that includes non-RRKM (Rice-Ramsperger
      Kassel-Marcus) effects due to slow intramolecular vibrational energy
      redistribution (IVR). The slow IVR effects are modeled by incorporating the
      theoretical results obtained recently by Leitner et al. (J. Phys. Chem. A 2003,
      107, 10706-10716), who used the local random matrix theory. The present results
      show that the experimental rate constants of Meyer et al. are described to within
      about a factor of 2 over much of the experimental pressure range. However, a
      number of assumptions and areas of disagreement will require further
      investigation. These include a discrepancy between the calculated and
      experimental thermal rate constants near zero pressure, a leveling off of the
      experimental rate constants that is not predicted by theory and which depends on
      the identity of the collider gas, the need to use rate constants for collision
      induced IVR that are larger than the estimated total collision rate constants,
      and the choice of barrier-crossing frequency. Despite these unsettled issues, the
      theory of Leitner et al. shows great promise for accounting for possible non-RRKM
      effects in an important class of reactions.

PMID- 16789778
TI  - Quantum mechanical investigation of the atmospheric reaction CH3O2 + NO.
AB  - The important stationary points on the potential energy surface of the reaction
      CH(3)O(2) + NO have been investigated using ab initio and density functional
      theory techniques. The optimizations were carried out at the B3LYP/6-311++G(d,p)
      and MP2/6-311++G(d,p) levels of theory while the energetics have been refined
      using the G2MP2, G3//B3LYP, and CCSD(T) methodologies. The calculations allow the
      proper characterization of the transition state barriers that determine the fate
      of the nascent association conformeric minima of methyl peroxynitrite. The main
      products, CH(3)O + NO(2), are formed through either rearrangement of the trans
      conformer to methyl nitrate and its subsequent dissociation or via the breaking
      of the peroxy bond of the cis-conformer to CH(3)O + NO(2) radical pair. The
      important consequences of the proposed mechanism are (a) the allowance on
      energetic grounds for nitrate formation parallel to radical propagation under
      favorable external conditions and (b) the confirmation of the conformational
      preference of the homolytic cleavage of the peroxy bond, discussed in previous
      literature.

PMID- 16789779
TI  - Dimers of and tautomerism between 2-pyrimidinethiol and 2(1H)-pyrimidinethione: a
      density functional theory (DFT) study.
AB  - Density functional theory (BLYP, B3LYP, B3P86, B3PW91) with the 6-31+G(d,p), 6
      311+G(d,p), and cc-pVTZ basis sets has been used to calculate structural
      parameters, relative energies, and vibrational spectra of 2-pyrimidinethiol (1)
      and 2(1H)-pyrimidinethione (2) and their hydrogen-bonded homodimers (C(2) 3,
      C(2h) [4](double dagger), C(2h) 5), monohydrates, and dihydrates and a
      heterodimer (6). Several transition state structures proposed for the
      tautomerization process have also been examined. At the B3PW91/6
      311+G(d,p)//B3PW91/6-31+G(d,p) level of theory 2-pyrimidinethiol (1) is predicted
      to be 3.41 kcal/mol more stable (E(rel)) than 2(1H)-pyrimidinethione (2) in the
      gas phase and 2 is predicted to be 6.47 kcal/mol more stable than 1 in aqueous
      medium. An unfavorable planar intramolecular strained four center transition
      state (TS1) for the tautomerization of 1 and 2 in the gas-phase lies 29.07
      kcal/mol higher in energy than 2-pyrimidinethiol (1). The C(2) 2-pyrimidinethiol
      dimer (3) is 6.84 kcal/mol lower in energy than the C(2) homodimer transition
      state structure ([11](double dagger)) that connects dimers 3 and 4. Transition
      state [11](double dagger) provides a facile pathway for tautomerization between 1
      and 2 in the gas phase (monomer-dimer promoted tautomerization). The hydrogen
      bonded 2-pyrimidinethiol- - -H(2)O and 2-pyrimidinethiol- - -2H(2)O structures
      are predicted to be 1.27 and 1.55 kcal/mol, respectively, higher in energy than
      2(1H)-pyrimidinethione- - -H(2)O and 2(1H)-pyrimidinethione- - -2H(2)O. Water
      promoted tautomerization via cyclic transition states involving one water
      molecule (TS- - -H(2)O, [12](double dagger)) and two water molecules (TS- - 
      2H(2)O, [13](double dagger)) lie 11.42 and 11.44 kcal/mol, respectively, higher
      in energy than 2-pyrimidinethiol- - -H(2)O and 2-pyrimidinethiol- - -2H(2)O.
      Thus, the hydrated transition states [12](double dagger) and [13](double dagger)
      are involved in the tautomerism between 1 and 2 in aqueous medium.

PMID- 16789780
TI  - Modern valence-bond-like representations of selected D6h "aromatic" rings.
AB  - Starting from CASSCF(6,6)/6-31G(d,p) wave functions, we consider different
      valence-bond (VB)-like interpretations of the pi electron systems for various
      (constrained) "benzene-like" D(6)(h)() rings, exploiting the invariance of the
      total wave function to arbitrary nonsingular transformations of the active
      orbitals. Quantities obtained rather directly from the various calculations
      provide a fairly consistent ordering of the degree of aromaticity: C(6)H(6)
      approximately B(6) > N(6) > Al(6) approximately Si(6)H(6) > P(6). Representations
      based on mutually orthogonal orbitals are found to be somewhat less satisfactory
      than those that have no such constraints on the overlaps between the active
      orbitals.

PMID- 16789781
TI  - Hydration and dissociation of hydrogen fluoric acid (HF).
AB  - The hydration and dissociation phenomena of HF(H(2)O)(n)() (n < or = 10) clusters
      have been studied by using both the density functional theory with the 6
      311++G[sp] basis set and the Moller-Plesset second-order perturbation theory with
      the aug-cc-pVDZ+(2s2p/2s) basis set. The structures for n > or = 8 are first
      reported here. The dissociated form of the hydrogen-fluoric acid in HF(H(2)O)(n)
      clusters is found to be less stable at 0 K than the undissociated form until n =
      10. HF may not be dissociated at 0 K solely by water molecules because the HF H
      bond is stronger than the OH H bond, against the expectation that the dissociated
      HF(H(2)O)(n) would be more stable than the undissociated one in the presence of a
      number of water molecules. The dissociation would be possible for only a fraction
      of a number of hydrated HF clusters by the Boltzmann distribution at finite
      temperatures. This is in sharp contrast to other hydrogen halide acids (HCl, HBr,
      HI) showing the dissociation phenomena at 0 K for n > or = 4. The IR spectra of
      dissociated and undissociated structures of HF(H(2)O)(n) are compared. The
      structures and binding energies of HF(H(2)O)(n) are found to be similar to those
      of (H(2)O)(n+1). It is interesting that HF(H(2)O)(n=5,6,10) are slightly less
      stable compared with other sizes of clusters, just like the fact that
      (H(2)O)(n=6,7,11) are slightly less stable. The present study would be useful for
      the experimental/spectroscopic investigation of not only the dissociation
      phenomena of HF but also the similarity of the HF-water clusters to the water
      clusters.

PMID- 16789782
TI  - Thermodynamic properties (enthalpy, bond energy, entropy, and heat capacity) and
      internal rotor potentials of vinyl alcohol, methyl vinyl ether, and their
      corresponding radicals.
AB  - Vinyl alcohols (enols) have been discovered as important intermediates and
      products in the oxidation and combustion of hydrocarbons, while methyl vinyl
      ethers are also thought to occur as important combustion intermediates. Vinyl
      alcohol has been detected in interstellar media, while poly(vinyl alcohol) and
      poly(methyl vinyl ether) are common polymers. The thermochemical property data on
      these vinyl alcohols and methyl vinyl ethers is important for understanding their
      stability, reaction paths, and kinetics in atmospheric and thermal hydrocarbon
      oxygen systems. Enthalpies , entropies , and heat capacities (C(p)()(T)) are
      determined for CH(2)=CHOH, C(*)H=CHOH, CH(2)=C(*)OH, CH(2)=CHOCH(3),
      C(*)H=CHOCH(3), CH(2)=C(*)OCH(3), and CH(2)=CHOC(*)H(2). Molecular structures,
      vibrational frequencies, , and C(p)(T) are calculated at the B3LYP/6-31G(d,p)
      density functional calculation level. Enthalpies are also determined using the
      composite CBS-Q, CBS-APNO, and G3 methods using isodesmic work reactions to
      minimize calculation errors. Potential barriers for internal rotors are
      calculated at the B3LYP/6-31G(d,p) level and used to determine the hindered
      internal rotational contributions to entropy and heat capacity. The recommended
      ideal gas phase values calculated in this study are the following (in kcal mol(
      1)): -30.0, -28.9 (syn, anti) for CH(2)=CHOH; -25.6, -23.9 for CH(2)=CHOCH(3);
      31.3, 33.5 for C(*)H=CHOH; 27.1 for anti-CH(2)=C(*)OH; 35.6, 39.3 for
      C(*)H=CHOCH(3); 33.5, 32.2 for CH(2)=C(*)OCH(3); 21.3, 22.0 for
      CH(2)=CHOC(*)H(2). Bond dissociation energies (BDEs) and group additivity
      contributions are also determined. The BDEs reveal that the O-H, O-CH(3), C-OH,
      and C-OCH(3) bonds in vinyl alcohol and methyl vinyl ether are similar in energy
      to those in the aromatic molecules phenol and methyl phenyl ether, being on
      average around 3 kcal mol(-1) weaker in the vinyl systems. The keto-enol
      tautomerization enthalpy for the interconversion of vinyl alcohol to acetaldehyde
      is determined to be -9.7 kcal mol(-1), while the activation energy for this
      reaction is calculated as 55.9 kcal mol(-1); this is the simplest keto-enol
      tautomerization and is thought to be important in the reactions of vinyl alcohol.
      Formation of the formyl methyl radical (vinoxy radical/vinyloxy radical) from
      both vinyl alcohol and methyl vinyl ether is also shown to be important, and its
      reactions are discussed briefly.

PMID- 16789783
TI  - Structural and photoluminescence properties of excited state intramolecular
      proton transfer capable compounds-potential emissive and electron transport
      materials.
AB  - Electronic factors influencing the photoluminescence properties and rates of
      excited state intramolecular proton transfer (ESIPT) reaction of o-hydroxy
      derivatives of 2,5-diphenyl-1,3,4-oxadiazole have been studied. The potential of
      these molecules as emissive and electron transport materials in designing
      improved organic light emitting diodes (OLEDs) has been studied by analyzing
      possible reasons for the unusually high Stokes shifts and ESIPT reaction rates.
      Time-dependent density functional theory (TDDFT) methods have been used to
      calculate the ground and excited state properties of the phototautomers that are
      the ESIPT reaction products. We study the relative effect of electron-withdrawing
      substituents on the proton-acceptor moiety and predict that the lowest ESIPT rate
      (1.9 x 10(11) s(-1)) is achieved with a dimethylamino substituent and that the
      Stokes shifts are around 11 000 cm(-1) for all three derivatives.

PMID- 16789784
TI  - Oxidative addition of hydrogen halides and dihalogens to Pd. Trends in reactivity
      and relativistic effects.
AB  - We have theoretically studied the oxidative addition of HX and X(2) to palladium
      for X = F, Cl, Br, I and At, using both nonrelativistic and ZORA-relativistic
      density functional theory at BLYP/QZ4P. The purpose is 3-fold: (i) to obtain a
      set of consistent potential energy surfaces (PESs) to infer accurate trends in
      reactivity for simple, archetypal oxidative addition reactions; (ii) to assess
      how relativistic effects modify these trends along X = F, Cl, Br, I and At; and
      (iii) to rationalize the trends in reactivity in terms of the reactants'
      molecular-orbital (MO) electronic structure and the H-X and X-X bond strengths.
      For the latter, we provide full Dirac-Coulomb CCSD(T) benchmarks. All oxidative
      additions to Pd are exothermic and have a negative overall barrier, except that
      of HF which is approximately thermoneutral and has a positive overall barrier.
      The activation barriers of the HX oxidative additions decrease systematically as
      X descends in group 17 of the periodic table; those of X(2) first increase, from
      F to Cl, but then also decrease further down group 17. On the other hand, HX and
      X(2) show clearly opposite trends regarding the heat of reaction: that of HX
      becomes more exothermic and that of X(2) less exothermic as X descends in group
      17. Relativistic effects can be as large as 15-20 kcal/mol but they do not change
      the qualitative trends. Interestingly, the influence of relativistic effects on
      activation barriers and heats of reaction decreases for the heavier halogens due
      to counteracting relativistic effects in palladium and the halogens.

PMID- 16789785
TI  - Chemical bonds without "chemical bonding"? A combined experimental and
      theoretical charge density study on an iron trimethylenemethane complex.
AB  - High-resolution X-ray diffraction data, in conjunction with DFT(B3LYP) quantum
      calculations, have been used in a QTAIM analysis of the charge density in the
      trimethylenemethane (TMM) complex Fe(eta(4)-C[CH(2)](3))(CO)(3). The agreement
      between the theoretical and experimental topological properties is excellent.
      Only one bond path is observed between the TMM ligand and the Fe atom, from the
      central C(alpha) atom. However, much evidence, including from the delocalization
      indices and the source function, suggests that there is a strong chemical
      interaction between the Fe and C(beta) atoms, despite the formal lack of chemical
      bonding according to QTAIM.

PMID- 16789786
TI  - Solid-state NMR spectra and long intradimer bonds in the pi-[TCNE]22- dianion.
AB  - The principal (13)C chemical-shift values for the pi-[TCNE](2)(2-) dimer anion
      within an array of counterions have been measured to understand better the
      electronic structure of these atypical chemical species in several related TCNE
      based structures. The structure of pi-[TCNE](2)(2-) is unusual as it contains two
      very long C-C bond lengths (ca. 2.9 Angstroms) between the two monomeric units
      and has been found to exist as a singlet state, suggestive of a (1)A(1g)
      (b(2u)(2)b(1g)(0)) electronic configuration. A systematic study of several
      oxidation states of [TCNE](n) (n = 0, 1-, 2-) was conducted to determine how the
      NMR chemical-shift tensor values change as a function of electronic structure and
      to understand the interactions that lead to spin-pairing of the monomer units.
      The density functional theory (DFT) calculated nuclear shielding tensors are
      correlated with the experimentally determined principal chemical-shift values.
      Such theoretical methods provide information on the tensor magnitudes and
      orientations of their principal tensor components with respect to the molecular
      frame. Both theoretical and experimental ethylenic chemical-shielding tensors
      reveal high sensitivity in the component, delta(perpendicular), lying in the
      monomer molecular plane and perpendicular to the pi-electron plane. This largest
      shift dependence on charge density is observed to be about -111 ppm/e(-) for
      delta(perpendicular). The component in the molecular plane but parallel to the
      central C=C bond, delta(parallel), exhibits a sensitivity of approximately -43
      ppm/e(-). However, the out-of-plane component delta'(perpendicular) shows a
      minimal dependence of -2.6 ppm/e(-) on the oxidation state (n) of [TCNE](n).
      These relative values support the claim that it is changes within the ethylenic
      pi-electrons and not the sigma-electrons that best account for the dramatic
      variations in bonding and shift tensors in this series of compounds. Concerning
      the intraion bonding, relatively weak Wiberg bond orders between the two
      monomeric components of the dimer correlate with the long bonds linking the two
      [TCNE(*)](-) monomers. The chemical-shift tensors for the cyano group, compared
      to the ethylene shifts, exhibit a reduced sensitivity on the TCNE oxidation
      state. The experimental principal chemical-shift components agree (within typical
      errors) with the calculated quantum mechanical shieldings used to correlate the
      bonding. The embedded ion model (EIM) was used to investigate the typically large
      electrostatic lattice potential in these ionic materials. Chemical-shielding
      principal values calculated with the EIM model differ from experiment by +/-3.82
      ppm on average, whereas in the absence of an electrostatic field model, the
      experimental and theoretical results agree by +/-4.42 ppm, which is only a modest
      increase in error considering the overall ionic magnitudes associated with the
      tensor variations. Apparently, the effects of the sizable long-range
      electrostatic fields cancel when the shifts are computed because of lattice
      symmetry.

PMID- 16789787
TI  - Probes of the metal-to-ligand charge-transfer excited states in ruthenium
      Am(m)ine-bipyridine complexes: the effects of NH/ND and CH/CD isotopic
      substitution on the 77 K luminescence.
AB  - The effects of ligand perdeuteration on the metal-to-ligand charge-transfer
      (MLCT) excited-state emission properties at 77 K are described for several
      [Ru(L)(4)bpy](2+) complexes in which the emission process is nominally [uIII,bpy
      ] --> [RuII,bpy]. The perdeuteration of the 2,2'-bipyridine (bpy) ligand is found
      to increase the zero-point energy differences between the ground states and MLCT
      excited states by amounts that vary from 0 +/- 10 to 70 +/- 10 cm(-1) depending
      on the ligands L. This indicates that there are some vibrational modes with
      smaller force constants in the excited states than in the ground states for most
      of these complexes. These blue shifts increase approximately as the energy
      difference between the excited and ground states decreases, but they are
      otherwise not strongly correlated with the number of bipyridine ligands in the
      complex. Careful comparisons of the [Ru(L)(4)(d(8)-bpy)](2+) and [Ru(L)(4)(h(8)
      bpy](2+) emission spectra are used to resolve the very weak vibronic
      contributions of the C-H stretching modes as the composite contributions of the
      corresponding vibrational reorganizational energies. The largest of these, 25 +/-
      10 cm(-1), is found for the complexes with L = py or bpy/2 and smaller when L =
      NH(3). Perdeuteration of the am(m)ine ligands (NH(3), en, or [14]aneN(4)) has no
      significant effect on the zero-point energy difference, and the contributions of
      the NH stretching vibrational modes to the emission band shape are too weak to
      resolve. Ligand perdeuteration does increase the excited-state lifetimes by a
      factor that is roughly proportional to the excited-state-ground-state energy
      difference, even though the CH and NH vibrational reorganizational energies are
      too small for nuclear tunneling involving these modes to dominate the relaxation
      process. It is proposed that metal-ligand skeletal vibrational modes and
      configurational mixing between metal-centered, bpy-ligand-centered, and MLCT
      excited states are important in determining the zero-point energy differences,
      while a large number of different combinations of relatively low-frequency
      vibrational modes must contribute to the nonradiative relaxation of the MLCT
      excited states.

PMID- 16789790
TI  - Treating ocular hypertension to reduce glaucoma risk: when to treat?
AB  - When to treat the patient who presents with ocular hypertension has been a
      question that has 'stumped' the ophthalmic community for decades. Population
      based studies and intervention trials have provided the basis for understanding
      why we consider treating such patients. Although the EGPS (European Glaucoma
      Prevention Study) did not demonstrate that reducing intraocular pressure (IOP)
      with dorzolamide prevented the onset of glaucoma compared with individuals
      receiving a placebo, the investigators of the OHTS (Ocular Hypertension Treatment
      Study) found that the treatment of ocular hypertension can be delayed with
      topical medication when treated patients were compared with an observation group.
      There are differences in inclusion criteria, study design and retention rates
      between the EGPS and the OHTS, which may have led to the discrepancies in
      outcomes between these two studies. These differences provide a basis for
      understanding the relevance of the findings of both trials to clinical practice.
      The clinician should consider key risk factors such as age, thin corneal
      thickness measurements, large cup-to-disc ratio and mean IOP when determining who
      should be treated. However, the ultimate decision of when to treat will be
      determined by other issues such as life expectancy, the general health of the
      patient and the number of risk factors. Clearly, the treatment of only high-risk
      patients with ocular hypertension should be considered.

PMID- 16789791
TI  - Chronic graft-versus-host disease: Pathogenesis and clinical management.
AB  - Chronic graft-versus-host disease (cGVHD) is the most common and severe
      complication among patients surviving >100 days after allogeneic transplantation.
      It starts with the expansion of donor T cells in response to alloantigens or
      autoantigens that are unchecked by normal thymic or peripheral mechanisms of
      deletion. The T cells induce damage to target organs either directly through
      cytolytic attack, inflammatory cytokines and fibrosis, or by promoting B cell
      activation and production of autoantibodies. HLA disparity, donor and patient age
      and sex, source of progenitor cells, graft composition and previous acute GVHD
      are the main factors that predict the risk of developing cGVHD. Once the
      diagnosis has been established, patients needing treatment (extensive cGVHD) must
      be identified. Poor prognostic factors such as extensive skin involvement,
      thrombocytopenia and progressive-type onset of cGVHD must be considered in order
      to define the immunosuppressive treatment requirements. Prednisone, together with
      a calcineurin inhibitor such as ciclosporin or tacrolimus, can be considered the
      standard regimen as primary treatment for cGVHD. Using that approach, among high
      risk patients (identified as those with extensive cGVHD plus thrombocytopenia) 3
      year survival reached 52%. Concerning salvage regimens, to date there is no clear
      standard regimen for cGVHD treatment, the best choice being to enter the patient
      into a clinical trial. Immunosuppressive drugs that inhibit T cell activation,
      proliferation or survival, such as mycophenolate mofetil, the anti-interleukin-2
      alpha receptor antagonist daclizumab, sirolimus (rapamycin), extracorporeal
      photopheresis and pentostatin (deoxycoformycin), among other agents, have been
      used with a very wide range of complete responses ranging from 5% to 50%. In
      addition, anti-cytokine or B cell inhibitors such as etanercept or rituximab have
      also been evaluated. The severe immunosuppression induced by those drugs
      increases the risk of infectious complications and may have a deleterious effect
      on the graft versus tumour effect after transplant so that newer strategies based
      on the selective depletion of alloreactive T cells and induction of more specific
      immunotolerance against host tissues are required.

PMID- 16789792
TI  - Cytotoxic chemotherapy for pancreatic cancer: Advances to date and future
      directions.
AB  - Chemotherapy remains the mainstay of treatment for pancreatic cancer as most
      patients present with advanced disease, which precludes locoregional treatment.
      However, the efficacy of chemotherapy is limited. Gemcitabine is the only agent
      that improves symptoms and confers a modest survival advantage. Many combination
      therapy regimens have been studied in phase II settings. Eleven randomised phase
      III trials have been conducted to compare gemcitabine-containing regimens with
      gemcitabine monotherapy since gemcitabine became available clinically. The
      combination of gemcitabine plus capecitabine has demonstrated a survival
      advantage over gemcitabine, whereas gemcitabine plus oxaliplatin and gemcitabine
      plus cisplatin have shown improved progression-free survival or time to tumour
      progression but failed to demonstrate a survival advantage over gemcitabine. The
      search for effective therapy for advanced pancreatic cancer continues.
      Gemcitabine in combination with cytotoxic agents or molecular targeted agents
      hold promise.

PMID- 16789793
TI  - Irritable bowel syndrome: recent and novel therapeutic approaches.
AB  - Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal
      disorder affecting up to 3-15% of the general population in Western countries. It
      is characterised by unexplained abdominal pain, discomfort and bloating in
      association with altered bowel habits. The pathophysiology of IBS is considered
      to be multifactorial, involving disturbances of the brain-gut-axis: IBS has been
      associated with abnormal gastrointestinal motor functions, visceral
      hypersensitivity, psychosocial factors, autonomic dysfunction and mucosal
      inflammation. Traditional IBS therapy is mainly symptom oriented and often
      unsatisfactory. Hence, there is a need for new treatment strategies. Increasing
      knowledge of brain-gut physiology, mechanisms, and neurotransmitters and
      receptors involved in gastrointestinal motor and sensory function have led to the
      development of several new therapeutic approaches. This article provides a
      systematic overview of recently approved or novel medications that show promise
      for the treatment of IBS; classification is based on the physiological systems
      targeted by the medication. The article includes agents acting on the serotonin
      receptor or serotonin transporter system, novel selective anticholinergics, alpha
      adrenergic agonists, opioid agents, cholecystokinin antagonists, neurokinin
      antagonists, somatostatin receptor agonists, neurotrophin-3, corticotropin
      releasing factor antagonists, chloride channel activators, guanylate cyclase-c
      agonists, melatonin and atypical benzodiazepines. Finally, the role of probiotics
      and antibacterials in the treatment of IBS is summarised.

PMID- 16789794
TI  - Antimicrobial agents in orthopaedic surgery: Prophylaxis and treatment.
AB  - The pathogenesis of implant-associated infection involves interaction between the
      microorganisms (biofilm formation), the implant and the host. Despite improvement
      of perioperative prophylaxis, orthopaedic implants still remain highly
      susceptible to bacterial or fungal contamination, generally resulting in
      persistent implant-associated infection. Therefore, perioperative and life-long
      prevention of infection is important. For perioperative prophylaxis, a first- or
      second-generation cephalosporin is recommended, which should be administered
      between 60 and 30 minutes before incision. The duration of prophylaxis should not
      exceed 1 day. In centres with a low incidence of infection, a single dose is
      sufficient. Treatment of infections associated with orthopaedic devices usually
      requires appropriate surgical intervention combined with prolonged antimicrobial
      therapy. The choice of the antimicrobial regimen depends on the duration and
      pathogenesis of infection, stability of the implant, antimicrobial susceptibility
      of the pathogen and condition of the surrounding soft tissue. The role of
      rifampicin (rifampin), which has excellent activity on adherent staphylococci, in
      combination with beta-lactams, glycopeptides, fluoroquinolones, minocycline,
      cotrimoxazole or fusidic acid, in the treatment of staphylococcal infections is
      outlined. Increasing antimicrobial resistance requires the use of alternative
      agents, such as quinupristin/dalfopristin, linezolid and daptomycin, but results
      of clinical trials with these agents are limited. Also reviewed are potential new
      antimicrobial agents currently undergoing investigation, such as the novel
      oxazolidinone RWJ-416457, the new glycopeptide dalbavancin, the glycylcycline
      compound tigecycline, the new carbacephem BP-102 and novel rifamycin derivatives.
      Vaccination against Staphylococcus aureus with StaphVAX induced specific
      antibodies potentially preventing bacteraemia; however, there are no studies on
      efficacy in the prophylaxis of device-associated infections with this vaccine.

PMID- 16789795
TI  - Zofenopril plus hydrochlorothiazide: Combination therapy for the treatment of
      mild to moderate hypertension.
AB  - Achieving target blood pressure (BP) levels in clinical practice is one of the
      main challenges for physicians in the management of patients with hypertension.
      It is now recognised that the majority of patients will require at least two
      antihypertensive drugs to achieve optimal BP control; the use of combination
      therapy as first-line treatment is also increasing as BP goals of
      antihypertensive therapy become more ambitious. The fixed combination of
      zofenopril/hydrochlorothiazide (HCTZ) 30/12.5 mg/day is approved in Italy,
      France, Switzerland and Greece for the management of mild to moderate
      hypertension. In clinical trials comparing zofenopril/HCTZ with each agent
      administered as monotherapy, combination therapy was more effective in
      normalising BP. This effect was particularly evident in one trial in which
      patients who were nonresponsive to zofenopril monotherapy were studied. In
      addition, in clinical trials to date, combination therapy provided sustained and
      consistent BP control over the entire 24-hour dose interval. Despite the greater
      efficacy of zofenopril/HCTZ 30/12.5 mg/day, when directly compared with each
      agent administered as monotherapy, there were no significant differences in the
      nature, severity or incidence of treatment-related adverse events; headache,
      dizziness, cough and polyuria were most frequently reported. Notably, in one
      study, fewer patients discontinued treatment with combination therapy than with
      zofenopril monotherapy due to adverse events. In conclusion, zofenopril/HCTZ
      30/12.5 mg/day provides more optimal BP control in a larger proportion of
      patients than would be achievable with monotherapy, while maintaining the
      tolerability profile observed with each individual agent, and thereby potentially
      enhancing patient compliance. The efficacy and safety profiles of this
      combination shown in clinical trials to date indicate that it will be a useful
      addition to currently available therapy for patients who have mild to moderate
      hypertension that is not adequately controlled by monotherapy, as well as for
      patients who require more rapid, intensive BP control.

PMID- 16789796
TI  - Methylphenidate transdermal system: In attention-deficit hyperactivity disorder
      in children.
AB  - The methylphenidate transdermal system (MTS) patch is approved by the US FDA for
      use in children aged 6-12 years with attention-deficit hyperactivity disorder
      (ADHD). This delivery system permits sustained absorption of the drug through the
      skin and into the bloodstream. Methylphenidate (MPH) is a CNS agent thought to
      act on dopamine and noradrenaline (norepinephrine) pathways and thereby blocks
      the reuptake of these neurotransmitters into the presynaptic neuron. In children
      with ADHD, MTS patches releasing MPH doses of 10-30 mg over a 9-hour period (12.5
      37.5 cm2 patch size) is steadily absorbed, with mean peak plasma concentrations
      of d-MPH (20-46.5 ng/mL) reached in approximately 8 hours. In well controlled
      trials in children with ADHD, patients administered MTS patches releasing MPH 10
      30 mg over approximately 9 hours showed significantly greater improvements in
      their ADHD symptoms than placebo recipients. MTS patches are generally well
      tolerated in paediatric patients with ADHD, with treatment-emergent events being
      similar in nature to those reported with oral MPH. The majority of adverse events
      were mild to moderate in intensity.

PMID- 16789798
TI  - Methylphenidate transdermal system in attention-deficit hyperactivity disorder in
      children: A viewpoint by Raul R. Silva.

PMID- 16789800
TI  - Inhaled mometasone furoate: A review of its use in persistent asthma in adults
      and adolescents.
AB  - Inhaled mometasone furoate (Asmanex) is a synthetic corticosteroid indicated for
      the first-line maintenance prophylactic therapy of persistent asthma in adults
      and adolescents. It is formulated for delivery via a breath-actuated dry powder
      inhaler (DPI) [Twisthaler].Inhaled mometasone furoate delivered by DPI is
      effective in treating patients with persistent asthma. It improves pulmonary
      function and health-related quality of life, reduces symptoms and decreases oral
      corticosteroid requirements in severe disease. It is a potent anti-inflammatory
      agent and is at least as clinically effective as other inhaled corticosteroids.
      Inhaled mometasone furoate is equally effective in controlling asthma when
      administered in two divided doses or as a single daily dose. Once-daily
      administration of mometasone furoate 200 microg in the evening was more effective
      than administration of the same dosage in the morning. The drug is well
      tolerated, with low systemic bioavailability and minimal systemic activity.
      Therefore, it is an effective and convenient option for controller therapy of
      persistent asthma in adults and adolescents.

PMID- 16789799
TI  - Eletriptan: a review of its use in the acute treatment of migraine.
AB  - Eletriptan (Relpax) is an orally administered, lipophilic, highly selective
      serotonin 5-HT(1B/1D) receptor agonist ('triptan') that is effective in the acute
      treatment of moderate to severe migraine attacks in adults. It has a rapid onset
      of action and demonstrates superiority over placebo as early as 30 minutes after
      the administration of a single 40 or 80 mg oral dose. The efficacy of eletriptan
      20 mg was similar to that of sumatriptan 100 mg, while eletriptan 40 and 80 mg
      displayed greater efficacy than sumatriptan 50 or 100 mg for most endpoints.
      Eletriptan 40 mg was generally superior to naratriptan 2.5 mg and equivalent to
      almotriptan 12.5 mg, rizatriptan 10 mg and zolmitriptan 2.5 mg, while eletriptan
      80 mg was superior to zolmitriptan 2.5 mg for most efficacy parameters.
      Eletriptan 40 and 80 mg were consistently superior to ergotamine/caffeine.
      Eletriptan is generally well tolerated, reduces time lost from normal activities,
      improves patients' health-related quality of life and appears to be at least as,
      if not more, cost effective than sumatriptan. Eletriptan is therefore a useful
      addition to the triptan family and a first-line treatment option in the acute
      management of migraine attacks.

PMID- 16789801
TI  - Investing in exposure.

PMID- 16789802
TI  - Hyperinfectivity in cholera: a new mechanism for an old epidemiological model?

PMID- 16789803
TI  - Industry and bioethics: what price the relationship?

PMID- 16789804
TI  - To fully tackle the gang of four, needs-driven R & D is essential.

PMID- 16789808
TI  - Merck's actions surrounding Vioxx.

PMID- 16789805
TI  - Response from Savioli and colleagues from the Department of Neglected Tropical
      Diseases, World Health Organization.

PMID- 16789811
TI  - Ultra-fast evaluation of protein energies directly from sequence.
AB  - The structure, function, stability, and many other properties of a protein in a
      fixed environment are fully specified by its sequence, but in a manner that is
      difficult to discern. We present a general approach for rapidly mapping sequences
      directly to their energies on a pre-specified rigid backbone, an important sub
      problem in computational protein design and in some methods for protein structure
      prediction. The cluster expansion (CE) method that we employ can, in principle,
      be extended to model any computable or measurable protein property directly as a
      function of sequence. Here we show how CE can be applied to the problem of
      computational protein design, and use it to derive excellent approximations of
      physical potentials. The approach provides several attractive advantages. First,
      following a one-time derivation of a CE expansion, the amount of time necessary
      to evaluate the energy of a sequence adopting a specified backbone conformation
      is reduced by a factor of 10(7) compared to standard full-atom methods for the
      same task. Second, the agreement between two full-atom methods that we tested and
      their CE sequence-based expressions is very high (root mean square deviation 1.1
      4.7 kcal/mol, R2 = 0.7-1.0). Third, the functional form of the CE energy
      expression is such that individual terms of the expansion have clear physical
      interpretations. We derived expressions for the energies of three classic protein
      design targets-a coiled coil, a zinc finger, and a WW domain-as functions of
      sequence, and examined the most significant terms. Single-residue and residue
      pair interactions are sufficient to accurately capture the energetics of the
      dimeric coiled coil, whereas higher-order contributions are important for the two
      more globular folds. For the task of designing novel zinc-finger sequences, a CE
      derived energy function provides significantly better solutions than a standard
      design protocol, in comparable computation time. Given these advantages, CE is
      likely to find many uses in computational structural modeling.

PMID- 16789812
TI  - How does cross-reactive stimulation affect the longevity of CD8+ T cell memory?
AB  - Immunological memory--the ability to "remember" previously encountered pathogens
      and respond faster upon re-exposure is a central feature of the immune response
      in vertebrates. The cross-reactive stimulation hypothesis for the maintenance of
      memory proposes that memory cells specific for a given pathogen are maintained by
      cross-reactive stimulation following infections with other (unrelated) pathogens.
      We use mathematical models to examine the cross-reactive stimulation hypothesis.
      We find that: (i) the direct boosting of cross-reactive lineages only provides a
      very small increase in the average longevity of immunological memory; (ii) the
      expansion of cross-reactive lineages can indirectly increase the longevity of
      memory by reducing the magnitude of expansion of new naive lineages which occupy
      space in the memory compartment and are responsible for the decline in memory;
      (iii) cross-reactive stimulation results in variation in the rates of decline of
      different lineages of memory cells and enrichment of memory cell population for
      cells that are cross-reactive for the pathogens to which the individual has been
      exposed.

PMID- 16789814
TI  - Integrated assessment and prediction of transcription factor binding.
AB  - Systematic chromatin immunoprecipitation (chIP-chip) experiments have become a
      central technique for mapping transcriptional interactions in model organisms and
      humans. However, measurement of chromatin binding does not necessarily imply
      regulation, and binding may be difficult to detect if it is condition or cofactor
      dependent. To address these challenges, we present an approach for reliably
      assigning transcription factors (TFs) to target genes that integrates many lines
      of direct and indirect evidence into a single probabilistic model. Using this
      approach, we analyze publicly available chIP-chip binding profiles measured for
      yeast TFs in standard conditions, showing that our model interprets these data
      with significantly higher accuracy than previous methods. Pooling the high
      confidence interactions reveals a large network containing 363 significant sets
      of factors (TF modules) that cooperate to regulate common target genes. In
      addition, the method predicts 980 novel binding interactions with high confidence
      that are likely to occur in so-far untested conditions. Indeed, using new chIP
      chip experiments we show that predicted interactions for the factors Rpn4p and
      Pdr1p are observed only after treatment of cells with methyl-methanesulfonate, a
      DNA-damaging agent. We outline the first approach for consistently integrating
      all available evidences for TF-target interactions and we comprehensively
      identify the resulting TF module hierarchy. Prioritizing experimental conditions
      for each factor will be especially important as increasing numbers of chIP-chip
      assays are performed in complex organisms such as humans, for which "standard
      conditions" are ill defined.

PMID- 16789813
TI  - Prioritizing genomic drug targets in pathogens: application to Mycobacterium
      tuberculosis.
AB  - We have developed a software program that weights and integrates specific
      properties on the genes in a pathogen so that they may be ranked as drug targets.
      We applied this software to produce three prioritized drug target lists for
      Mycobacterium tuberculosis, the causative agent of tuberculosis, a disease for
      which a new drug is desperately needed. Each list is based on an individual
      criterion. The first list prioritizes metabolic drug targets by the uniqueness of
      their roles in the M. tuberculosis metabolome ("metabolic chokepoints") and their
      similarity to known "druggable" protein classes (i.e., classes whose activity has
      previously been shown to be modulated by binding a small molecule). The second
      list prioritizes targets that would specifically impair M. tuberculosis, by
      weighting heavily those that are closely conserved within the Actinobacteria
      class but lack close homology to the host and gut flora. M. tuberculosis can
      survive asymptomatically in its host for many years by adapting to a dormant
      state referred to as "persistence." The final list aims to prioritize potential
      targets involved in maintaining persistence in M. tuberculosis. The rankings of
      current, candidate, and proposed drug targets are highlighted with respect to
      these lists. Some features were found to be more accurate than others in
      prioritizing studied targets. It can also be shown that targets can be
      prioritized by using evolutionary programming to optimize the weights of each
      desired property. We demonstrate this approach in prioritizing persistence
      targets.

PMID- 16789815
TI  - Parametric alignment of Drosophila genomes.
AB  - The classic algorithms of Needleman-Wunsch and Smith-Waterman find a maximum a
      posteriori probability alignment for a pair hidden Markov model (PHMM). To
      process large genomes that have undergone complex genome rearrangements, almost
      all existing whole genome alignment methods apply fast heuristics to divide
      genomes into small pieces that are suitable for Needleman-Wunsch alignment. In
      these alignment methods, it is standard practice to fix the parameters and to
      produce a single alignment for subsequent analysis by biologists. As the number
      of alignment programs applied on a whole genome scale continues to increase, so
      does the disagreement in their results. The alignments produced by different
      programs vary greatly, especially in non-coding regions of eukaryotic genomes
      where the biologically correct alignment is hard to find. Parametric alignment is
      one possible remedy. This methodology resolves the issue of robustness to changes
      in parameters by finding all optimal alignments for all possible parameters in a
      PHMM. Our main result is the construction of a whole genome parametric alignment
      of Drosophila melanogaster and Drosophila pseudoobscura. This alignment draws on
      existing heuristics for dividing whole genomes into small pieces for alignment,
      and it relies on advances we have made in computing convex polytopes that allow
      us to parametrically align non-coding regions using biologically realistic
      models. We demonstrate the utility of our parametric alignment for biological
      inference by showing that cis-regulatory elements are more conserved between
      Drosophila melanogaster and Drosophila pseudoobscura than previously thought. We
      also show how whole genome parametric alignment can be used to quantitatively
      assess the dependence of branch length estimates on alignment parameters.

PMID- 16789817
TI  - Assessing the accuracy of ancestral protein reconstruction methods.
AB  - The phylogenetic inference of ancestral protein sequences is a powerful technique
      for the study of molecular evolution, but any conclusions drawn from such studies
      are only as good as the accuracy of the reconstruction method. Every inference
      method leads to errors in the ancestral protein sequence, resulting in
      potentially misleading estimates of the ancestral protein's properties. To assess
      the accuracy of ancestral protein reconstruction methods, we performed
      computational population evolution simulations featuring near-neutral evolution
      under purifying selection, speciation, and divergence using an off-lattice
      protein model where fitness depends on the ability to be stable in a specified
      target structure. We were thus able to compare the thermodynamic properties of
      the true ancestral sequences with the properties of "ancestral sequences"
      inferred by maximum parsimony, maximum likelihood, and Bayesian methods.
      Surprisingly, we found that methods such as maximum parsimony and maximum
      likelihood that reconstruct a "best guess" amino acid at each position
      overestimate thermostability, while a Bayesian method that sometimes chooses less
      probable residues from the posterior probability distribution does not. Maximum
      likelihood and maximum parsimony apparently tend to eliminate variants at a
      position that are slightly detrimental to structural stability simply because
      such detrimental variants are less frequent. Other properties of ancestral
      proteins might be similarly overestimated. This suggests that ancestral
      reconstruction studies require greater care to come to credible conclusions
      regarding functional evolution. Inferred functional patterns that mimic
      reconstruction bias should be reevaluated.

PMID- 16789816
TI  - On modeling HIV and T cells in vivo: assessing causal estimators in vaccine
      trials.
AB  - The first efficacy trials--named STEP--of a T cell vaccine against HIV/AIDS began
      in 2004. The unprecedented structure of these trials raised new modeling and
      statistical challenges. Is it plausible that memory T cells, as opposed to
      antibodies, can actually prevent infection? If they fail at prevention, to what
      extent can they ameliorate disease? And how do we estimate efficacy in a vaccine
      trial with two primary endpoints, one traditional, one entirely novel (viral load
      after infection), and where the latter may be influenced by selection bias due to
      the former? In preparation for the STEP trials, biostatisticians developed novel
      techniques for estimating a causal effect of a vaccine on viral load, while
      accounting for post-randomization selection bias. But these techniques have not
      been tested in biologically plausible scenarios. We introduce new stochastic
      models of T cell and HIV kinetics, making use of new estimates of the rate that
      cytotoxic T lymphocytes--CTLs; the so-called killer T cells--can kill HIV
      infected cells. Based on these models, we make the surprising discovery that it
      is not entirely implausible that HIV-specific CTLs might prevent infection--as
      the designers explicitly acknowledged when they chose the endpoints of the STEP
      trials. By simulating thousands of trials, we demonstrate that the new
      statistical methods can correctly identify an efficacious vaccine, while
      protecting against a false conclusion that the vaccine exacerbates disease. In
      addition to uncovering a surprising immunological scenario, our results
      illustrate the utility of mechanistic modeling in biostatistics.

PMID- 16789818
TI  - A community resource benchmarking predictions of peptide binding to MHC-I
      molecules.
AB  - Recognition of peptides bound to major histocompatibility complex (MHC) class I
      molecules by T lymphocytes is an essential part of immune surveillance. Each MHC
      allele has a characteristic peptide binding preference, which can be captured in
      prediction algorithms, allowing for the rapid scan of entire pathogen proteomes
      for peptide likely to bind MHC. Here we make public a large set of 48,828
      quantitative peptide-binding affinity measurements relating to 48 different
      mouse, human, macaque, and chimpanzee MHC class I alleles. We use this data to
      establish a set of benchmark predictions with one neural network method and two
      matrix-based prediction methods extensively utilized in our groups. In general,
      the neural network outperforms the matrix-based predictions mainly due to its
      ability to generalize even on a small amount of data. We also retrieved
      predictions from tools publicly available on the internet. While differences in
      the data used to generate these predictions hamper direct comparisons, we do
      conclude that tools based on combinatorial peptide libraries perform remarkably
      well. The transparent prediction evaluation on this dataset provides tool
      developers with a benchmark for comparison of newly developed prediction methods.
      In addition, to generate and evaluate our own prediction methods, we have
      established an easily extensible web-based prediction framework that allows
      automated side-by-side comparisons of prediction methods implemented by experts.
      This is an advance over the current practice of tool developers having to
      generate reference predictions themselves, which can lead to underestimating the
      performance of prediction methods they are not as familiar with as their own. The
      overall goal of this effort is to provide a transparent prediction evaluation
      allowing bioinformaticians to identify promising features of prediction methods
      and providing guidance to immunologists regarding the reliability of prediction
      tools.

PMID- 16789819
TI  - Inference of disease-related molecular logic from systems-based microarray
      analysis.
AB  - Computational analysis of gene expression data from microarrays has been useful
      for medical diagnosis and prognosis. The ability to analyze such data at the
      level of biological modules, rather than individual genes, has been recognized as
      important for improving our understanding of disease-related pathways. It has
      proved difficult, however, to infer pathways from microarray data by deriving
      modules of multiple synergistically interrelated genes, rather than individual
      genes. Here we propose a systems-based approach called Entropy Minimization and
      Boolean Parsimony (EMBP) that identifies, directly from gene expression data,
      modules of genes that are jointly associated with disease. Furthermore, the
      technique provides insight into the underlying biomolecular logic by inferring a
      logic function connecting the joint expression levels in a gene module with the
      outcome of disease. Coupled with biological knowledge, this information can be
      useful for identifying disease-related pathways, suggesting potential therapeutic
      approaches for interfering with the functions of such pathways. We present an
      example providing such gene modules associated with prostate cancer from publicly
      available gene expression data, and we successfully validate the results on
      additional independently derived data. Our results indicate a link between
      prostate cancer and cellular damage from oxidative stress combined with
      inhibition of apoptotic mechanisms normally triggered by such damage.

PMID- 16789820
TI  - Adaptation to different human populations by HIV-1 revealed by codon-based
      analyses.
AB  - Several codon-based methods are available for detecting adaptive evolution in
      protein-coding sequences, but to date none specifically identify sites that are
      selected differentially in two populations, although such comparisons between
      populations have been historically useful in identifying the action of natural
      selection. We have developed two fixed effects maximum likelihood methods: one
      for identifying codon positions showing selection patterns that persist in a
      population and another for detecting whether selection is operating
      differentially on individual codons of a gene sampled from two different
      populations. Applying these methods to two HIV populations infecting genetically
      distinct human hosts, we have found that few of the positively selected amino
      acid sites persist in the population; the other changes are detected only at the
      tips of the phylogenetic tree and appear deleterious in the long term.
      Additionally, we have identified seven amino acid sites in protease and reverse
      transcriptase that are selected differentially in the two samples, demonstrating
      specific population-level adaptation of HIV to human populations.

PMID- 16789822
TI  - Moving forward moving backward: directional sorting of chemotactic cells due to
      size and adhesion differences.
AB  - Differential movement of individual cells within tissues is an important yet
      poorly understood process in biological development. Here we present a
      computational study of cell sorting caused by a combination of cell adhesion and
      chemotaxis, where we assume that all cells respond equally to the chemotactic
      signal. To capture in our model mesoscopic properties of biological cells, such
      as their size and deformability, we use the Cellular Potts Model, a multiscale,
      cell-based Monte Carlo model. We demonstrate a rich array of cell-sorting
      phenomena, which depend on a combination of mescoscopic cell properties and
      tissue level constraints. Under the conditions studied, cell sorting is a fast
      process, which scales linearly with tissue size. We demonstrate the occurrence of
      "absolute negative mobility", which means that cells may move in the direction
      opposite to the applied force (here chemotaxis). Moreover, during the sorting,
      cells may even reverse the direction of motion. Another interesting phenomenon is
      "minority sorting", where the direction of movement does not depend on cell type,
      but on the frequency of the cell type in the tissue. A special case is the cAMP
      wave-driven chemotaxis of Dictyostelium cells, which generates pressure waves
      that guide the sorting. The mechanisms we describe can easily be overlooked in
      studies of differential cell movement, hence certain experimental observations
      may be misinterpreted.

PMID- 16789821
TI  - Molecular simulations of cotranslational protein folding: fragment stabilities,
      folding cooperativity, and trapping in the ribosome.
AB  - Although molecular simulation methods have yielded valuable insights into
      mechanistic aspects of protein refolding in vitro, they have up to now not been
      used to model the folding of proteins as they are actually synthesized by the
      ribosome. To address this issue, we report here simulation studies of three model
      proteins: chymotrypsin inhibitor 2 (CI2), barnase, and Semliki forest virus
      protein (SFVP), and directly compare their folding during ribosome-mediated
      synthesis with their refolding from random, denatured conformations. To calibrate
      the methodology, simulations are first compared with in vitro data on the folding
      stabilities of N-terminal fragments of CI2 and barnase; the simulations reproduce
      the fact that both the stability and thermal folding cooperativity increase as
      fragments increase in length. Coupled simulations of synthesis and folding for
      the same two proteins are then described, showing that both fold essentially post
      translationally, with mechanisms effectively identical to those for refolding. In
      both cases, confinement of the nascent polypeptide chain within the ribosome
      tunnel does not appear to promote significant formation of native structure
      during synthesis; there are however clear indications that the formation of
      structure within the nascent chain is sensitive to location within the ribosome
      tunnel, being subject to both gain and loss as the chain lengthens.
      Interestingly, simulations in which CI2 is artificially stabilized show a
      pronounced tendency to become trapped within the tunnel in partially folded
      conformations: non-cooperative folding, therefore, appears in the simulations to
      exert a detrimental effect on the rate at which fully folded conformations are
      formed. Finally, simulations of the two-domain protease module of SFVP, which
      experimentally folds cotranslationally, indicate that for multi-domain proteins,
      ribosome-mediated folding may follow different pathways from those taken during
      refolding. Taken together, these studies provide a first step toward developing
      more realistic methods for simulating protein folding as it occurs in vivo.

PMID- 16789823
TI  - Lysine 63-polyubiquitination guards against translesion synthesis-induced
      mutations.
AB  - Eukaryotic cells possess several mechanisms to protect the integrity of their DNA
      against damage. These include cell-cycle checkpoints, DNA-repair pathways, and
      also a distinct DNA damage-tolerance system that allows recovery of replication
      forks blocked at sites of DNA damage. In both humans and yeast, lesion bypass and
      restart of DNA synthesis can occur through an error-prone pathway activated
      following mono-ubiquitination of proliferating cell nuclear antigen (PCNA), a
      protein found at sites of replication, and recruitment of specialized translesion
      synthesis polymerases. In yeast, there is evidence for a second, error-free,
      pathway that requires modification of PCNA with non-proteolytic lysine 63-linked
      polyubiquitin (K63-polyUb) chains. Here we demonstrate that formation of K63
      polyUb chains protects human cells against translesion synthesis-induced
      mutations by promoting recovery of blocked replication forks through an
      alternative error-free mechanism. Furthermore, we show that polyubiquitination of
      PCNA occurs in UV-irradiated human cells. Our findings indicate that K63
      polyubiquitination guards against environmental carcinogenesis and contributes to
      genomic stability.

PMID- 16789825
TI  - Genetic screens for mutations affecting development of Xenopus tropicalis.
AB  - We present here the results of forward and reverse genetic screens for chemically
      induced mutations in Xenopus tropicalis. In our forward genetic screen, we have
      uncovered 77 candidate phenotypes in diverse organogenesis and differentiation
      processes. Using a gynogenetic screen design, which minimizes time and husbandry
      space expenditures, we find that if a phenotype is detected in the gynogenetic F2
      of a given F1 female twice, it is highly likely to be a heritable abnormality
      (29/29 cases). We have also demonstrated the feasibility of reverse genetic
      approaches for obtaining carriers of mutations in specific genes, and have
      directly determined an induced mutation rate by sequencing specific exons from a
      mutagenized population. The Xenopus system, with its well-understood embryology,
      fate map, and gain-of-function approaches, can now be coupled with efficient loss
      of-function genetic strategies for vertebrate functional genomics and
      developmental genetics.

PMID- 16789824
TI  - The life-cycle of operons.
AB  - Operons are a major feature of all prokaryotic genomes, but how and why operon
      structures vary is not well understood. To elucidate the life-cycle of operons,
      we compared gene order between Escherichia coli K12 and its relatives and
      identified the recently formed and destroyed operons in E. coli. This allowed us
      to determine how operons form, how they become closely spaced, and how they die.
      Our findings suggest that operon evolution may be driven by selection on gene
      expression patterns. First, both operon creation and operon destruction lead to
      large changes in gene expression patterns. For example, the removal of lysA and
      ruvA from ancestral operons that contained essential genes allowed their
      expression to respond to lysine levels and DNA damage, respectively. Second, some
      operons have undergone accelerated evolution, with multiple new genes being added
      during a brief period. Third, although genes within operons are usually closely
      spaced because of a neutral bias toward deletion and because of selection against
      large overlaps, genes in highly expressed operons tend to be widely spaced
      because of regulatory fine-tuning by intervening sequences. Although operon
      evolution may be adaptive, it need not be optimal: new operons often comprise
      functionally unrelated genes that were already in proximity before the operon
      formed.

PMID- 16789827
TI  - Allele-specific KRT1 expression is a complex trait.
AB  - The differential expression of alleles occurs commonly in humans and is likely an
      important genetic factor underlying heritable differences in phenotypic traits.
      Understanding the molecular basis of allelic expression differences is thus an
      important challenge. Although many genes have been shown to display differential
      allelic expression, this is the first study to examine in detail the cumulative
      effects of multiple cis-regulatory polymorphisms responsible for allele-specific
      expression differences. We have used a variety of experimental approaches to
      identify and characterize cis-regulatory polymorphisms responsible for the
      extreme allele-specific expression differences of keratin-1 (KRT1) in human white
      blood cells. The combined data from our analyses provide strong evidence that the
      KRT1 allelic expression differences result from the haplotypic combinations and
      interactions of five cis-regulatory single nucleotide polymorphisms (SNPs) whose
      alleles differ in their affinity to bind transcription factors and modulate KRT1
      promoter activity. Two of these cis-regulatory SNPs bind transcriptional
      activators with the alleles on the high-expressing KRT1 haplotype pattern having
      a higher affinity than the alleles on the low-expressing haplotype pattern. In
      contrast, the other three cis-regulatory SNPs bind transcriptional inhibitors
      with the alleles on the low-expressing haplotype pattern having a higher affinity
      than the alleles on the high-expressing haplotype pattern. Our study provides
      important new insights into the degree of complexity that the cis-regulatory
      sequences responsible for allele-specific transcriptional regulation have. These
      data suggest that allelic expression differences result from the cumulative
      contribution of multiple DNA sequence polymorphisms, with each having a small
      effect, and that allele-specific expression can thus be viewed as a complex
      trait.

PMID- 16789826
TI  - Who ate whom? Adaptive Helicobacter genomic changes that accompanied a host jump
      from early humans to large felines.
AB  - Helicobacter pylori infection of humans is so old that its population genetic
      structure reflects that of ancient human migrations. A closely related species,
      Helicobacter acinonychis, is specific for large felines, including cheetahs,
      lions, and tigers, whereas hosts more closely related to humans harbor more
      distantly related Helicobacter species. This observation suggests a jump between
      host species. But who ate whom and when did it happen? In order to resolve this
      question, we determined the genomic sequence of H. acinonychis strain Sheeba and
      compared it to genomes from H. pylori. The conserved core genes between the
      genomes are so similar that the host jump probably occurred within the last
      200,000 (range 50,000-400,000) years. However, the Sheeba genome also possesses
      unique features that indicate the direction of the host jump, namely from early
      humans to cats. Sheeba possesses an unusually large number of highly fragmented
      genes, many encoding outer membrane proteins, which may have been destroyed in
      order to bypass deleterious responses from the feline host immune system. In
      addition, the few Sheeba-specific genes that were found include a cluster of
      genes encoding sialylation of the bacterial cell surface carbohydrates, which
      were imported by horizontal genetic exchange and might also help to evade host
      immune defenses. These results provide a genomic basis for elucidating molecular
      events that allow bacteria to adapt to novel animal hosts.

PMID- 16789828
TI  - Nuclear mRNA degradation pathway(s) are implicated in Xist regulation and X
      chromosome inactivation.
AB  - A critical step in X-chromosome inactivation (XCI), which results in the dosage
      compensation of X-linked gene expression in mammals, is the coating of the
      presumptive inactive X chromosome by the large noncoding Xist RNA, which then
      leads to the recruitment of other factors essential for the
      heterochromatinisation of the inactive X and its transcriptional silencing. In an
      approach aimed at identifying genes implicated in the X-inactivation process by
      comparative transcriptional profiling of female and male mouse gastrula, we
      identified the Eif1 gene involved in translation initiation and RNA degradation.
      We show here that female embryonic stem cell lines, silenced by RNA interference
      for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and
      fail to undergo X-inactivation. To probe further an effect involving RNA
      degradation pathways, the inhibition by RNA interference of Rent1, a factor
      essential for nonsense-mediated decay and Exosc10, a specific nuclear component
      of the exosome, was analysed and shown to similarly impair Xist upregulation and
      XCI. In Eif1-, Rent1-, and Exosc10-interfered clones, Xist spliced form(s) are
      strongly downregulated, while the levels of unspliced form(s) of Xist and the
      stability of Xist RNA remain comparable to that of the control cell lines. Our
      data suggests a role for mRNA nuclear degradation pathways in the critical
      regulation of spliced Xist mRNA levels and the onset of the X-inactivation
      process.

PMID- 16789829
TI  - The dynamics of homologous pairing during mating type interconversion in budding
      yeast.
AB  - Cells repair most double-strand breaks (DSBs) that arise during replication or by
      environmental insults through homologous recombination, a high-fidelity process
      critical for maintenance of genomic integrity. However, neither the detailed
      mechanism of homologous recombination nor the specific roles of critical
      components of the recombination machinery-such as Bloom and Werner syndrome
      proteins-have been resolved. We have taken a novel approach to examining the
      mechanism of homologous recombination by tracking both a DSB and the template
      from which it is repaired during the repair process in individual yeast cells.
      The two loci were labeled with arrays of DNA binding sites and visualized in live
      cells expressing green fluorescent protein-DNA binding protein chimeras.
      Following induction of an endonuclease that introduces a DSB next to one of the
      marked loci, live cells were imaged repeatedly to determine the relative
      positions of the DSB and the template locus. We found a significant increase in
      persistent associations between donor and recipient loci following formation of
      the DSB, demonstrating DSB-induced pairing between donor and template. However,
      such associations were transient and occurred repeatedly in every cell, a result
      not predicted from previous studies on populations of cells. Moreover, these
      associations were absent in sgs1 or srs2 mutants, yeast homologs of the Bloom and
      Werner syndrome genes, but were enhanced in a rad54 mutant, whose protein product
      promotes efficient strand exchange in vitro. Our results indicate that a DSB
      makes multiple and reversible contacts with a template during the repair process,
      suggesting that repair could involve interactions with multiple templates,
      potentially creating novel combinations of sequences at the repair site. Our
      results further suggest that both Sgs1 and Srs2 are required for efficient
      completion of recombination and that Rad54 may serve to dissociate such
      interactions. Finally, these results demonstrate that mechanistic insights into
      recombination not accessible from studies of populations of cells emerge from
      observations of individual cells.

PMID- 16789830
TI  - Genome-wide analysis of gene expression during early Arabidopsis flower
      development.
AB  - Detailed information about stage-specific changes in gene expression is crucial
      for the understanding of the gene regulatory networks underlying development.
      Here, we describe the global gene expression dynamics during early flower
      development, a key process in the life cycle of a plant, during which floral
      patterning and the specification of floral organs is established. We used a novel
      floral induction system in Arabidopsis, which allows the isolation of a large
      number of synchronized floral buds, in conjunction with whole-genome microarray
      analysis to identify genes with differential expression at distinct stages of
      flower development. We found that the onset of flower formation is characterized
      by a massive downregulation of genes in incipient floral primordia, which is
      followed by a predominance of gene activation during the differentiation of
      floral organs. Among the genes we identified as differentially expressed in the
      experiment, we detected a significant enrichment of closely related members of
      gene families. The expression profiles of these related genes were often highly
      correlated, indicating similar temporal expression patterns. Moreover, we found
      that the majority of these genes is specifically up-regulated during certain
      developmental stages. Because co-expressed members of gene families in
      Arabidopsis frequently act in a redundant manner, these results suggest a high
      degree of functional redundancy during early flower development, but also that
      its extent may vary in a stage-specific manner.

PMID- 16789832
TI  - Transcriptional profiling of aging in human muscle reveals a common aging
      signature.
AB  - We analyzed expression of 81 normal muscle samples from humans of varying ages,
      and have identified a molecular profile for aging consisting of 250 age-regulated
      genes. This molecular profile correlates not only with chronological age but also
      with a measure of physiological age. We compared the transcriptional profile of
      muscle aging to previous transcriptional profiles of aging in the kidney and the
      brain, and found a common signature for aging in these diverse human tissues. The
      common aging signature consists of six genetic pathways; four pathways increase
      expression with age (genes in the extracellular matrix, genes involved in cell
      growth, genes encoding factors involved in complement activation, and genes
      encoding components of the cytosolic ribosome), while two pathways decrease
      expression with age (genes involved in chloride transport and genes encoding
      subunits of the mitochondrial electron transport chain). We also compared
      transcriptional profiles of aging in humans to those of the mouse and fly, and
      found that the electron transport chain pathway decreases expression with age in
      all three organisms, suggesting that this may be a public marker for aging across
      species.

PMID- 16789831
TI  - Exploring the mycobacteriophage metaproteome: phage genomics as an educational
      platform.
AB  - Bacteriophages are the most abundant forms of life in the biosphere and carry
      genomes characterized by high genetic diversity and mosaic architectures. The
      complete sequences of 30 mycobacteriophage genomes show them collectively to
      encode 101 tRNAs, three tmRNAs, and 3,357 proteins belonging to 1,536 "phamilies"
      of related sequences, and a statistical analysis predicts that these represent
      approximately 50% of the total number of phamilies in the mycobacteriophage
      population. These phamilies contain 2.19 proteins on average; more than half
      (774) of them contain just a single protein sequence. Only six phamilies have
      representatives in more than half of the 30 genomes, and only three-encoding tape
      measure proteins, lysins, and minor tail proteins-are present in all 30 phages,
      although these phamilies are themselves highly modular, such that no single amino
      acid sequence element is present in all 30 mycobacteriophage genomes. Of the
      1,536 phamilies, only 230 (15%) have amino acid sequence similarity to previously
      reported proteins, reflecting the enormous genetic diversity of the entire phage
      population. The abundance and diversity of phages, the simplicity of phage
      isolation, and the relatively small size of phage genomes support bacteriophage
      isolation and comparative genomic analysis as a highly suitable platform for
      discovery-based education.

PMID- 16789833
TI  - Impact of bacterial genetics on the transmission of isoniazid-resistant
      Mycobacterium tuberculosis.
AB  - Understanding the ecology of drug-resistant pathogens is essential for devising
      rational programs to preserve the effective lifespan of antimicrobial agents and
      to abrogate epidemics of drug-resistant organisms. Mathematical models predict
      that strain fitness is an important determinant of multidrug-resistant
      Mycobacterium tuberculosis transmission, but the effects of strain diversity have
      been largely overlooked. Here we compared the impact of resistance mutations on
      the transmission of isoniazid-resistant M. tuberculosis in San Francisco during a
      9-y period. Strains with a KatG S315T or inhA promoter mutation were more likely
      to spread than strains with other mutations. The impact of these mutations on the
      transmission of isoniazid-resistant strains was comparable to the effect of other
      clinical determinants of transmission. Associations were apparent between
      specific drug resistance mutations and the main M. tuberculosis lineages. Our
      results show that in addition to host and environmental factors, strain genetic
      diversity can influence the transmission dynamics of drug-resistant bacteria.

PMID- 16789834
TI  - Prevalence of local immune response against oral infection in a
      Drosophila/Pseudomonas infection model.
AB  - Pathogens have developed multiple strategies that allow them to exploit host
      resources and resist the immune response. To study how Drosophila flies deal with
      infectious diseases in a natural context, we investigated the interactions
      between Drosophila and a newly identified entomopathogen, Pseudomonas
      entomophila. Flies orally infected with P. entomophila rapidly succumb despite
      the induction of both local and systemic immune responses, indicating that this
      bacterium has developed specific strategies to escape the fly immune response.
      Using a combined genetic approach on both host and pathogen, we showed that P.
      entomophila virulence is multi-factorial with a clear differentiation between
      factors that trigger the immune response and those that promote pathogenicity. We
      demonstrate that AprA, an abundant secreted metalloprotease produced by P.
      entomophila, is an important virulence factor. Inactivation of aprA attenuated
      both the capacity to persist in the host and pathogenicity. Interestingly, aprA
      mutants were able to survive to wild-type levels in immune-deficient Relish
      flies, indicating that the protease plays an important role in protection against
      the Drosophila immune response. Our study also reveals that the major
      contribution to the fly defense against P. entomophila is provided by the local,
      rather than the systemic immune response. More precisely, our data points to an
      important role for the antimicrobial peptide Diptericin against orally infectious
      Gram-negative bacteria, emphasizing the critical role of local antimicrobial
      peptide expression against food-borne pathogens.

PMID- 16789835
TI  - Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus
      induced acute pneumonia.
AB  - Influenza A virus (IAV) is the etiological agent of a highly contagious acute
      respiratory disease that causes epidemics and considerable mortality annually.
      Recently, we demonstrated, using an in vitro approach, that the pattern
      recognition Toll-like receptor (TLR)3 plays a key role in the immune response of
      lung epithelial cells to IAV. In view of these data and the fact that the
      functional role of TLR3 in vivo is still debated, we designed an investigation to
      better understand the role of TLR3 in the mechanisms of IAV pathogenesis and host
      immune response using an experimental murine model. The time-course of several
      dynamic parameters, including animal survival, respiratory suffering, viral
      clearance, leukocyte recruitment into the airspaces and secretion of critical
      inflammatory mediators, was compared in infected wild-type and TLR3(-/-) mice.
      First, we found that the pulmonary expression of TLR3 is constitutive and
      markedly upregulated following influenza infection in control mice. Notably, when
      compared to wild-type mice, infected TLR3-/- animals displayed significantly
      reduced inflammatory mediators, including RANTES (regulated upon activation,
      normal T cell expressed and secreted), interleukin-6, and interleukin-12p40/p70
      as well as a lower number of CD8+ T lymphocytes in the bronchoalveolar airspace.
      More important, despite a higher viral production in the lungs, mice deficient in
      TLR3 had an unexpected survival advantage. Hence, to our knowledge, our findings
      show for the first time that TLR3-IAV interaction critically contributes to the
      debilitating effects of a detrimental host inflammatory response.

PMID- 16789836
TI  - Host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse
      model: role of the innate antiviral immune response.
AB  - The severe combined immunodeficiency disorder (SCID)-beige/albumin (Alb)
      urokinase plasminogen activator (uPA) mouse containing a human-mouse chimeric
      liver is currently the only small animal model capable of supporting hepatitis C
      virus (HCV) infection. This model was utilized to characterize the host
      transcriptional response to HCV infection. The purpose of these studies was to
      investigate the genetic component of the host response to HCV infection and also
      to distinguish virus-induced gene expression changes from adaptive HCV-specific
      immune-mediated effects. Gene expression profiles from HCV-infected mice were
      also compared to those from HCV-infected patients. Analyses of the gene
      expression data demonstrate that host factors regulate the response to HCV
      infection, including the nature of the innate antiviral immune response. They
      also indicate that HCV mediates gene expression changes, including regulation of
      lipid metabolism genes, which have the potential to be directly cytopathic,
      indicating that liver pathology may not be exclusively mediated by HCV-specific
      adaptive immune responses. This effect appears to be inversely related to the
      activation of the innate antiviral immune response. In summary, the nature of the
      initial interferon response to HCV infection may determine the extent of viral
      mediated effects on host gene expression.

PMID- 16789837
TI  - Anopheles gambiae immune responses to human and rodent Plasmodium parasite
      species.
AB  - Transmission of malaria is dependent on the successful completion of the
      Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in
      the midgut tissue, where most parasites are killed by the mosquito's immune
      system. In the present study, DNA microarray analyses have been used to compare
      Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete
      stage of the human pathogen Plasmodium falciparum and the rodent experimental
      model pathogen P. berghei. Invasion by P. berghei had a more profound impact on
      the mosquito transcriptome, including a variety of functional gene classes, while
      P. falciparum elicited a broader immune response at the gene transcript level.
      Ingestion of human malaria-infected blood lacking invasive ookinetes also induced
      a variety of immune genes, including several anti-Plasmodium factors. Twelve
      selected genes were assessed for effect on infection with both parasite species
      and bacteria using RNAi gene silencing assays, and seven of these genes were
      found to influence mosquito resistance to both parasite species. An MD2-like
      receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating
      only resistance to P. falciparum, while the antimicrobial peptide gambicin and a
      novel putative short secreted peptide, IRSP5, were more specific for defense
      against the rodent parasite P. berghei. While all the genes that affected
      Plasmodium development also influenced mosquito resistance to bacterial
      infection, four of the antimicrobial genes had no effect on Plasmodium
      development. Our study shows that the impact of P. falciparum and P. berghei
      infection on A. gambiae biology at the gene transcript level is quite diverse,
      and the defense against the two Plasmodium species is mediated by antimicrobial
      factors with both universal and Plasmodium-species specific activities.
      Furthermore, our data indicate that the mosquito is capable of sensing infected
      blood constituents in the absence of invading ookinetes, thereby inducing anti
      Plasmodium immune responses.

PMID- 16789838
TI  - Schistosoma mansoni TGF-beta receptor II: role in host ligand-induced regulation
      of a schistosome target gene.
AB  - Members of transforming growth factor-beta (TGF-beta) superfamily play pivotal
      roles in development in multicellular organisms. We report the functional
      characterization of the Schistosoma mansoni type II receptor (SmTbetaRII). Mining
      of the S. mansoni expressed sequence tag (EST) database identified an EST clone
      that shows homology to the kinase domain of type II receptors from different
      species. The amplified EST sequence was used as a probe to isolate a cDNA clone
      spanning the entire coding region of a type II serine/threonine kinase receptor.
      The interaction of SmTbetaRII with SmTbetaRI was elucidated and shown to be
      dependent on TGF-beta ligand binding. Furthermore, in the presence of human TGF
      beta1, SmTbetaRII was able to activate SmTbetaRI, which in turn activated SmSmad2
      and promoted its interaction with SmSmad4, proving the transfer of the signal
      from the receptor complex to the Smad proteins. Gynaecophoral canal protein
      (GCP), whose expression in male worms is limited to the gynaecophoric canal, was
      identified as a potential TGF-beta target gene in schistosomes. Knocking down the
      expression of SmTbetaRII using short interfering RNA molecules (siRNA) resulted
      in a concomitant reduction in the expression of GCP. These data provide evidence
      for the direct involvement of SmTbetaRII in mediating TGF-beta-induced activation
      of the TGF-beta target gene, SmGCP, within schistosome parasites. The results
      also provide additional evidence for a role for the TGF-beta signaling pathway in
      male-induced female reproductive development.

PMID- 16789839
TI  - CCR5 is essential for NK cell trafficking and host survival following Toxoplasma
      gondii infection.
AB  - The host response to intracellular pathogens requires the coordinated action of
      both the innate and acquired immune systems. Chemokines play a critical role in
      the trafficking of immune cells and transitioning an innate immune response into
      an acquired response. We analyzed the host response of mice deficient in the
      chemokine receptor CCR5 following infection with the intracellular protozoan
      parasite Toxoplasma gondii. We found that CCR5 controls recruitment of natural
      killer (NK) cells into infected tissues. Without this influx of NK cells, tissues
      from CCR5-deficient (CCR5-/-) mice were less able to generate an inflammatory
      response, had decreased chemokine and interferon gamma production, and had higher
      parasite burden. As a result, CCR5-/- mice were more susceptible to infection
      with T. gondii but were less susceptible to the immune-mediated tissue injury
      seen in certain inbred strains. Adoptive transfer of CCR5+/+ NK cells into CCR5-/
      mice restored their ability to survive lethal T. gondii infection and
      demonstrated that CCR5 is required for NK cell homing into infected liver and
      spleen. This study establishes CCR5 as a critical receptor guiding NK cell
      trafficking in host defense.

PMID- 16789841
TI  - Retroviral DNA integration: viral and cellular determinants of target-site
      selection.
AB  - Retroviruses differ in their preferences for sites for viral DNA integration in
      the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates
      preferentially within active transcription units, whereas murine leukemia virus
      (MLV) integrates preferentially near transcription start sites and CpG islands.
      We investigated the viral determinants of integration-site selection using HIV
      chimeras with MLV genes substituted for their HIV counterparts. We found that
      transferring the MLV integrase (IN) coding region into HIV (to make HIVmIN)
      caused the hybrid to integrate with a specificity close to that of MLV. Addition
      of MLV gag (to make HIVmGagmIN) further increased the similarity of target-site
      selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag) displayed
      targeting preferences different from that of both HIV and MLV, further
      implicating Gag proteins in targeting as well as IN. We also report a genome-wide
      analysis indicating that MLV, but not HIV, favors integration near DNase I
      hypersensitive sites (i.e., +/- 1 kb), and that HIVmIN and HIVmGagmIN also
      favored integration near these features. These findings reveal that IN is the
      principal viral determinant of integration specificity; they also reveal a new
      role for Gag-derived proteins, and strengthen models for integration targeting
      based on tethering of viral IN proteins to host proteins.

PMID- 16789843
TI  - Photoreactions of cytochrome C oxidase.
AB  - The photoreduction of oxidized bovine heart cytochrome c oxidase (CcO) by visible
      and UV radiation was investigated in the absence and presence of external
      reagents. In the former case, the quantum yields for direct photoreduction of
      heme A (heme a + heme a(3)) were 2.6 +/- 0.5 x 10(-3), 4 +/- 1 x 10(-4), and 4 +/
      2 x 10(-6) with pulsed laser irradiation at 266, 355 and 532 nm, respectively.
      Within experimental uncertainty, the quantum yields did not depend on pulse
      energy, implying that the mechanism is monophotonic. Irradiation with 355 nm
      light resulted in spectral changes similar to those produced independently by
      reduction with dithionite, whereby the low-spin heme a and Cu(A) are reduced
      first. Extended illumination at 355 and 532 nm yielded substantial amounts of
      reduced heme a(3). Heme decomposition was noted with 266 nm light. In the
      presence of formate and cyanide ions, which bind at the binuclear heme
      a(3)/copper center in CcO, irradiation at 355 nm caused selective reduction of
      only the low-spin heme a and Cu(A). The addition of ferrioxalate ion dramatically
      increased the efficiency of cytochrome c oxidase photoreduction. The quantum
      efficiency for heme A reduction was found to be near unity, significantly greater
      than for other known methods of photoreduction. The active reductant is most
      likely ferrous iron, and its reduction of the enzyme is thermodynamically driven
      by the reformation of ferrioxalate in the presence of excess oxalate ion. Other
      metalloenzymes with redox potentials similar to those of cytochrome c oxidase
      should be amenable to indirect photoreduction by this method.

PMID- 16789840
TI  - A systematic map of genetic variation in Plasmodium falciparum.
AB  - Discovering novel genes involved in immune evasion and drug resistance in the
      human malaria parasite, Plasmodium falciparum, is of critical importance to
      global health. Such knowledge may assist in the development of new effective
      vaccines and in the appropriate use of antimalarial drugs. By performing a full
      genome scan of allelic variability in 14 field and laboratory strains of P.
      falciparum, we comprehensively identified approximately 500 genes evolving at
      higher than neutral rates. The majority of the most variable genes have paralogs
      within the P. falciparum genome and may be subject to a different evolutionary
      clock than those without. The group of 211 variable genes without paralogs
      contains most known immunogens and a few drug targets, consistent with the idea
      that the human immune system and drug use is driving parasite evolution. We also
      reveal gene-amplification events including one surrounding pfmdr1, the P.
      falciparum multidrug-resistance gene, and a previously uncharacterized
      amplification centered around the P. falciparum GTP cyclohydrolase gene, the
      first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is
      not the known target of any current drugs, downstream members of the pathway are
      targeted by several widely used antimalarials. We speculate that an amplification
      of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase
      flux through this pathway and facilitate parasite resistance to antifolate drugs.

PMID- 16789844
TI  - Isothiocyanato boron dipyrromethenes--the first BODIPY analogues of fluorescein
      isothiocyanate.
AB  - Two boron complexes of 5-phenyldipyrromethenes bearing isothiocyanate groups on
      the phenyl ring have been synthesized for the first time. The utility of these
      new fluorescence probes for labeling biologically relevant proteins is
      demonstrated on two monoclonal antibodies that bind to antigens overexpressed on
      cancer cells. Spectral comparison of the two structures reveals significant
      photophysical differences, including bathochromically shifted excitation and
      emission bands, increased molar absorptivity and a large increase in fluorescence
      quantum yield of approximately 10 times. Differences in photophysical parameters
      are linked to hindered rotation of the phenyl ring in one of the probes.

PMID- 16789851
TI  - The experts speak. Burn-out among HIV care providers. Interview by Vicki Glaser.

PMID- 16789852
TI  - Use of and exposure to HIV prevention programs and services by persons at high
      risk for HIV.
AB  - Although HIV information is widely available in this country, little is known
      about how commonly used HIV prevention activities reach persons at highest risk
      for HIV. In this paper, we describe the extent to which HIV prevention strategies
      reach a sample of high-risk persons and whether such exposure correlates with
      having been tested for HIV. Data are from the 2000 HIV Testing Survey, an
      anonymous interview study of men who have sex with men (MSM), injection drug
      users (IDU), and high-risk heterosexuals (HRH), recruited from appropriate venues
      in seven states and New York City. We report the proportion of persons exposed to
      three types of interventions: information (media messages, brochures), counseling
      or skills-building (group counseling, role play, calling an AIDS hotline), and
      prevention supplies (provision of condoms, bleach kits), stratified by HIV
      testing status (ever, never). Exposure to information interventions was high
      among 2491 respondents (85%-96%) and did not differ by testing status. Use of
      counseling or skills-building interventions varied by testing status for IDU (8%
      untested versus 41% tested, p < 0.01) and HRH (14% versus 20%, p = 0.03) but not
      MSM (15% versus 23%, p = 0.08). Among tested IDU, those receiving bleach kits
      were more likely to report consistent bleach use when injecting with nonsterile
      needles (25% versus 9%, p = 0.003). Exposure to HIV prevention information is
      high but exposure to counseling or skills-building interventions is less common
      and more prevalent among those previously tested. Prevention initiatives should
      focus on counseling and testing, skills-building, and prevention supplies.

PMID- 16789842
TI  - Antibody-independent control of gamma-herpesvirus latency via B cell induction of
      anti-viral T cell responses.
AB  - B cells can use antibody-dependent mechanisms to control latent viral infections.
      It is unknown whether this represents the sole function of B cells during chronic
      viral infection. We report here that hen egg lysozyme (HEL)-specific B cells can
      contribute to the control of murine gamma-herpesvirus 68 (gammaHV68) latency
      without producing anti-viral antibody. HEL-specific B cells normalized defects in
      T cell numbers and proliferation observed in B cell-/- mice during the early
      phase of gammaHV68 latency. HEL-specific B cells also reversed defects in CD8 and
      CD4 T cell cytokine production observed in B cell-/- mice, generating CD8 and CD4
      T cells necessary for control of latency. Furthermore, HEL-specific B cells were
      able to present virally encoded antigen to CD8 T cells. Therefore, B cells have
      antibody independent functions, including antigen presentation, that are
      important for control of gamma-herpesvirus latency. Exploitation of this property
      of B cells may allow enhanced vaccine responses to chronic virus infection.

PMID- 16789853
TI  - Type of substance use and access to HIV-related health care.
AB  - HIV-infected substance users have poorer health outcomes than other HIV risk
      groups. Few studies have examined the impact of specific types of substance use
      on health care. This study investigated the associations between specific types
      of substances of abuse and access to health care. HIV-infected individuals living
      in eight different single room occupancy hotels in the Bronx, New York, were
      interviewed between August 1999 and February 2001 regarding demographics, health
      care access and utilization, and drug and alcohol use. Of the 238 participants,
      the majority were male (59%), black or Hispanic (93%), and active drug users
      (61%). Individuals reporting any drug or crack/cocaine use were less likely to
      have a regular provider than those reporting no drug or no crack/cocaine use
      (adjusted odds ratio [AOR] = 0.50, p = 0.05; AOR =0.35, p = 0.004, respectively),
      while those with binge alcohol use were more likely to have a regular doctor than
      those without binge alcohol use (AOR = 2.61, p = 0.05). Individuals reporting any
      drug or crack/cocaine use were also less likely to perceive quality of health
      care positively (AOR = 0.50, p = 0.02; AOR = 0.37, p = 0.002, respectively).
      Heroin use, and injection drug use were not associated with these outcomes. When
      the sample was limited to recent drug users, similar patterns were found.
      Although drug use in general is associated with negative health outcomes, in this
      study, poorer measures of access to health care among substance users was
      associated predominantly with crack/cocaine use. It is important that clinicians
      and researchers working with substance-using populations understand how specific
      types of substance use differentially impact on health care.

PMID- 16789854
TI  - A pilot study of health beliefs and attitudes concerning measures of
      antiretroviral adherence among prisoners receiving directly observed
      antiretroviral therapy.
AB  - High level adherence to antiretroviral therapy (ART) is required to achieve and
      maintain suppression of HIV replication. Although directly observed therapy (DOT)
      has been suggested as an intervention to improve adherence, there is a paucity of
      data describing the attitudes and beliefs regarding DOT for ART among HIV
      infected individuals. This study was designed to evaluate the acceptability and
      psychometric properties of a survey instrument for use in assessing barriers and
      facilitators of adherence to ART DOT in prison. From July 1, 1999 to April 1,
      2000, we piloted an interviewer-administered questionnaire to assess health
      beliefs and attitudes regarding HIV treatment among 65 HIV-infected prison
      inmates receiving one or more of their antiretrovirals via directly observed
      therapy (DOT). The first 24 participants were administered the questionnaire to
      determine the feasibility of surveying prisoners in a correctional setting. There
      were no adherence data collected on these participants. The remaining 41
      participants had their adherence measured in addition to receiving the
      questionnaire. Thirty-one were included in the final analysis because 10 did not
      complete the study. Multiple antiretroviral adherence measures (electronic device
      medication monitoring [eDEM] caps, medication administration records [MARs], and
      pill counts) were assessed among a subset of the participants (n = 31) and
      correlated to the instrument response items. The median internal consistency
      reliability coefficient for the multi-item scales was 0.79. The strongest
      correlation between inmates' beliefs and their adherence was between "positive
      beliefs about protease inhibitors" and the MAR adherence measure (r = 0.72; p <
      0.001). This study provides preliminary support for the psychometric properties
      of the survey in this correctional setting.

PMID- 16789855
TI  - Barriers to antiretroviral adherence: the importance of depression, abuse, and
      other traumatic events.
AB  - Among HIV-infected persons, high-level adherence to antiretroviral medications
      (>90%-95%) is associated with improved immunologic, virologic, and clinical
      outcomes, and is necessary to prevent the emergence of viral resistance. This
      study examines whether lifetime traumatic events including physical and sexual
      abuse, are associated with antiretroviral nonadherence. We present a cross
      sectional analysis of the Coping with HIV/AIDS in the Southeast (CHASE) Study,
      analyzing data from the enrollment interview and medical records of study
      subjects. The CHASE Study is a prospective cohort study of consecutively sampled
      HIV-infected subjects from infectious diseases clinics in five southern states;
      Alabama, Georgia, Louisiana, North Carolina, and South Carolina. Four hundred
      seventy-four (78%) of the 611 CHASE study subjects reported being treated with
      antiretroviral medications at enrollment and are included in this analysis.
      Nonadherence was defined as the patient's self-report of missing any doses of
      their antiretroviral medications over the previous 7 days. Among study subjects,
      54% reported a history of physical and/or sexual abuse, 91% reported at least one
      lifetime traumatic event, and 24% reported nonadherence with their
      antiretrovirals. In multivariable logistic regression analysis, the number of
      categories of lifetime traumatic events (p = 0.03), the Addiction Severity Index
      (ASI) alcohol score (p = 0.02), and being uninsured (p = 0.04) were associated
      with antiretroviral nonadherence. The finding that lifetime traumatic events are
      associated with antiretroviral nonadherence, particularly among those who have
      been traumatized in multiple ways, highlights the complex and often persisting
      manifestations of such trauma and calls for further investigation.

PMID- 16789856
TI  - Caregiver psychosocial characteristics and children's adherence to antiretroviral
      therapy.
AB  - Although parents and caregivers may have primary responsibility for their
      children's medication- taking, surprisingly few studies have examined caregiver
      psychosocial correlates of children's adherence to antiretroviral therapy (ART).
      This cross-sectional, descriptive study examined the relationship between
      caregiver psychosocial characteristics and medication adherence among children
      with HIV. Fifty-four caregivers of children with HIV completed a demographic
      questionnaire, the Parenting Stress Index, the Brief Symptom Inventory, the
      Family Support Scale, and the Support Functions Scale. Adherence to ART was
      measured with children's 6-month pharmacy refill histories. Children and
      caregivers were primarily African American, urban, and poor (63% reported
      <$15,000 annual household income). Univariate analyses showed that an adherent
      classification (>/= 80% refill rate) was associated with shorter duration of
      highly active antiretroviral therapy (HAART) treatment, nondisclosure of the HIV
      diagnosis to the child, lower caregiver income level, having a nonbiologically
      related caregiver, and less caregiver psychiatric distress. In a multivariate
      logistic regression, duration of child's HAART treatment, child HIV disclosure
      status, caregiver income, and caregiver psychiatric distress accounted for 63% of
      the variance in adherence. Findings highlight the complexity of children's
      adherence to ART and the need for multicenter studies with greater sample sizes
      to explore in more detail the effects of caregiver psychological distress and
      child HIV disclosure status on adherence as well as the ways in which regimen
      fatigue and adherence fluctuate over time.

PMID- 16789857
TI  - The use of cell phone reminder calls for assisting HIV-infected adolescents and
      young adults to adhere to highly active antiretroviral therapy: a pilot study.
AB  - Long-term medication regimen adherence is challenging in all populations, but in
      the HIV-infected adolescent population the frequency of poverty, homelessness,
      substance abuse, and mental illness make highly active antiretroviral therapy
      (HAART) adherence even more challenging. In 2003, we developed a pilot program
      for HIV-infected adolescents and young adults between the ages of 16 and 24 who
      were either going to begin a HAART regimen for the first time or begin a new
      HAART regimen. Participants received a free cell phone with a local service plan
      for approximately 6 months. Participants received phone call reminders for 12
      weeks. Call frequency was tapered at 4-week intervals. Patients were assessed at
      4-week intervals to determine the perceived intrusiveness or helpfulness of
      receiving calls, and missed medication doses. Eight consecutive patients were
      recruited for the study, and five were able to complete it through the 24 weeks.
      Most participants found the calls to be helpful and the level of intrusion into
      their daily lives acceptable. Using cell phone reminders to assist patients does
      not require an extensive amount of daily staff time. Tapering calls rapidly over
      3 months, followed by discontinuation of calls provided inadequate support for
      subjects, especially those with significant psychosocial issues such as substance
      abuse. Use of cell phone reminders to assist adolescents adhere with HIV
      medications was practical and acceptable to pilot study participants. Viral
      suppression waned for all but two patients after termination of cell phone
      reminders and suggests that a 12-week intervention was not adequate for most
      subjects. Larger prospective studies of cell phone observation of therapy will be
      needed to determine if this intervention can improve long-term adherence and
      health outcomes.

PMID- 16789858
TI  - One in ten have resistance.

PMID- 16789859
TI  - Microbicide update.

PMID- 16789861
TI  - When a body meets a body: a neo-Kleinian view of language and bodily experience.

PMID- 16789860
TI  - The forgotten self: with the use of Bion's theory of negative links.

PMID- 16789862
TI  - In the beginning was love?

PMID- 16789863
TI  - A clinical approach to transforming enactment.

PMID- 16789864
TI  - Constructing infants: anthropological realities and analytic horizons.

PMID- 16789865
TI  - Talking with strangers.

PMID- 16789866
TI  - Treatment of dissociative identity disorder: "tortured child syndrome".

PMID- 16789867
TI  - Opening psychoanalytic space to the spiritual.

PMID- 16789869
TI  - Politics masquerading as science.

PMID- 16789872
TI  - Efflux pumps in drug resistance of Candida.
AB  - The incidences of human pathogenic yeast Candida albicans and its related species
      acquiring resistance to antifungals have increased considerably, which poses
      serious problems towards its successful chemotherapy. The resistance of these
      pathogenic fungi is not restricted to the commonly used triazole compounds but is
      even encountered, though not often, with polyene derivatives as well. The efflux
      pump proteins belonging to ABC (ATP Binding Cassette) and MFS (Major
      Facilitators) super family are the most prominent contributors of multidrug
      resistance (MDR) in yeasts. The abundance of the drug transporters and their
      wider specificity suggest that these transporters may not be exclusively drug
      exporters in yeasts and may have other cellular functions. In this article we
      focus on some of the recent advances on the structure and function, evolution and
      transcriptional control of drug efflux proteins of Candida. A short discussion on
      the physiological relevance of drug transporters is also included.

PMID- 16789873
TI  - Phospho-MurNAc-pentapeptide translocase (MraY) as a target for antibacterial
      agents and antibacterial proteins.
AB  - Phospho-MurNAc-pentapeptide translocase (MraY, translocase I) catalyses the first
      step of the lipid-linked cycle of reactions of bacterial peptidoglycan
      biosynthesis. MraY is the target for five families of nucleoside antibacterial
      natural products: the tunicamycins, the mureidomycins (also pacidamycins,
      napsamycins), the liposidomycins, the muraymycins, and the capuramycins. Recent
      structure-activity studies on these families have led to the identification of
      active pharmacophores, and insight into their mechanisms of action. This step of
      peptidoglycan biosynthesis is also the target for the bacteriolytic E protein
      from bacteriophage phiX174, and for cyclic peptides of the amphomycin family
      which complex the undecaprenyl phosphate co-substrate. The mechanisms of enzyme
      inhibition by these agents are discussed, and the state of knowledge regarding
      the transmembrane structure, active site, and catalytic mechanism of MraY. The
      availability of high throughput assays and prospects of MraY as an antibacterial
      target are also discussed.

PMID- 16789874
TI  - Recent developments in drug targets and delivery of anti-HIV drugs.
AB  - With almost 40 million people infected with human immunodeficiency virus (HIV),
      it is one of the most devastating diseases with no cure in sight. Over the past
      two decades, significant progress has been made to identify and validate drug
      targets for HIV. However, most of the 20 FDA approved drugs are targeted to two
      enzymes; reverse transcriptase and protease. Other drug targets derived from HIV
      and host factors are being validated, and novel compounds are being developed to
      overcome drug resistance. Recent data indicate that low and residual virus found
      in tissues of the lymphoid and central nervous system (CNS) is likely due to
      insufficient drug levels. Thus, improvement in the delivery of anti-HIV drugs to
      these tissues with limited drug penetration or accumulation, is equally important
      to maximally suppress viral replication. Novel lipid associated drugs (i.e.
      indinavir) targeted to the lymphoid tissue have been shown to overcome limited
      drug exposure in the lymph nodes and to further reduce residual virus in tissue.
      This review discusses viral and cellular targets that could interrupt viral
      replication, as well as novel and proven strategies to enhance the delivery of
      anti-HIV drugs to the lymphoid, CNS, and cells where low viral replication and
      limited drug levels exist.

PMID- 16789875
TI  - Targets and tools: recent advances in the development of anti-HCV nucleic acids.
AB  - Hepatitis C virus (HCV), the major etiological agent of transfusion-associated
      non-A, non-B hepatitis, is a severe health problem affecting up to 3% of the
      world population. Since its identification in 1989, enormous efforts have been
      made to characterize the viral cycle. However, many details regarding the virus'
      penetration of hepatocytes, its replication and translation, and the assembling
      of virions remain unknown, mostly because of a lack of an efficient culture
      system. This has also hampered the development of fully effective antiviral
      drugs. Current treatments based on the combination of interferon and ribavirin
      trigger a sustained virological response in only 40% of infected individuals,
      thus the development of alternative therapeutic strategies is a major research
      goal. Nucleic acid based therapeutic agents may be of some potential in hepatitis
      C treatment. In recent years, much effort has gone into the improvement of DNA
      and RNA molecules as specific gene silencing tools. This review summarizes the
      state of the art in the development of new HCV therapies, paying special
      attention to those involving antisense oligonucleotides, aptamers, ribozymes,
      decoys and siRNA inhibitors. The identification of potential viral targets is
      also discussed.

PMID- 16789876
TI  - Combating vancomycin resistance in bacteria: targeting the D-ala-D-ala
      dipeptidase VanX.
AB  - In the past 20 years, vancomycin and other glycopeptide antibiotics have been
      administered to patients with Streptococcal and Staphylococcal infections that
      were resistant to all other antibiotics or to patients who were allergic to
      penicillins and cephalosporins. After extensive use of vancomycin and other
      glycopeptide antibiotics in humans, several strains of Enterococcus have
      developed high-level vancomycin resistance (collectively called VRE, vancomycin
      resistant Enterococcus), and this resistance phenotype has spread to other
      organisms. The spread of vancomycin resistance to other pathogens and,
      potentially, to bacterial strains on the CDC's bioterrorism watch list is a major
      biomedical concern. Bacteria most often become resistant to vancomycin by
      acquiring a transposon containing genes that encode for a number of proteins,
      five of which are essential for the high-level resistance phenotype. The five
      essential gene products are called VanR, VanS, VanH, VanA, and VanX. Previous
      studies have shown that the inactivation of VanX results in an organism that is
      sensitive to vancomycin and that VanX is an excellent inhibitor target. In this
      review the known inhibitors and structural and mechanistic properties of VanX
      will be discussed. These data will be used to offer suggestions for novel,
      rationally-designed or -redesigned inhibitors, which could potentially be used in
      combination with existing glycopeptide antibiotics as a treatment for vancomycin
      resistant bacterial infections.

PMID- 16789877
TI  - New trends in development of antimycobacterial compounds.
AB  - The resurgence of tuberculosis and the surge of multidrug-resistant clinical
      isolates of Mycobacterium tuberculosis have reaffirmed tuberculosis as a primary
      public health concern. In this review we describe some new findings on the
      pharmacological status of fluoroquinolones derivatives (Gatifloxacin,
      Moxifloxacin and Sitafloxacin), new macrolides (Clarithromycin, Azithromycin and
      Roxithromycin), new rifamycin derivatives (Rifapentin, Rifabutin and Rifalazil)
      and new oxazolidinones (Linezolid and PNU 100480). We describe also other type of
      agents that are being developed as antimycobacterial drugs. Some of these are
      under clinical investigation, while others are considered to be promising
      candidates for future development. Among them, nitroimidazopyrans, new ketolides,
      Isoxyl (ISO), pyrroles derived from BM 212, Mefloquine and Diarylquinoline
      R207910 are discussed. We also describe the mechanism of drug resistance in
      mycobacteria, as well as new potential targets.

PMID- 16789878
TI  - Novel approaches to antimalarial drug discovery.
AB  - Major advances in our understanding of malaria parasite biology have been made.
      Coupled with the completion of the malaria genome, this has presented exciting
      opportunities for target-based antimalarial drug discovery. However, the
      unraveling of more validated biological targets will not necessarily translate
      into the identification of new chemical entities that are effective against drug
      resistant parasites in the long term. As history has already shown, development
      of antiplasmodial agents aimed at a single parasite target or specialized process
      has failed to stem the tide of drug resistance. This review highlights recent
      starting points and/or approaches to antimalarial drug discovery with particular
      emphasis on innovative efforts, which are not necessarily based on the
      identification of new drug targets and attendant inhibitor design. Approaches
      covered include utilization of validated chemical scaffolds, bioprecursor and
      carrier prodrugs, double drug development and/or multi-therapeutic strategies,
      use of metallocenic scaffolds, the medicinal chemistry of antimalarial natural
      products and in silico drug design.

PMID- 16789880
TI  - Synthesis of A/B-ring partial analogs of bruceantin as potential antimalarial
      agents.
AB  - Bruceantin (1), a classical quassinoid with the highest reported antimalarial
      activity among the quassinoids examined thus far, was selected as a natural
      product lead for the design of a series of A/B-ring analogs. A viable strategy
      for the synthesis of the series was developed. The functionalized A-ring and the
      C-15 ester moiety in bruceantin are incorporated in all designed compounds. The
      preliminary bioassay results will be discussed in detail.

PMID- 16789882
TI  - Novel experimental design for steady-state processes: a systematic Bayesian
      approach for enzymes, drug transport, receptor binding, continuous culture and
      cell transport kinetics.
AB  - We demonstrate that a Bayesian approach (the use of prior knowledge) to the
      design of steady-state experiments can produce major gains quantifiable in terms
      of information, productivity and accuracy of each experiment. Developing the use
      of Bayesian utility functions, we have used a systematic method to identify the
      optimum experimental designs for a number of kinetic model data sets. This has
      enabled the identification of trends between kinetic model types, sets of design
      rules and the key conclusion that such designs should be based on some prior
      knowledge of the kinetic model. We suggest an optimal and iterative method for
      selecting features of the design such as the substrate range, number of
      measurements and choice of intermediate points. The final design collects data
      suitable for accurate modelling and analysis and minimises the error in the
      parameters estimated. It is equally applicable to enzymes, drug transport,
      receptor binding, microbial culture and cell transport kinetics.

PMID- 16789881
TI  - A novel achiral seco-amino-cyclopropylindoline (CI) analog of CC-1065 and the
      duocarmycins: design, synthesis and biological studies.
AB  - The design, synthesis and DNA binding properties of a novel achiral and amino
      containing seco-cyclopropylindoline analog (seco-amino-CI-TMI, 1) of the
      duocarmycins are described. Thermal induced DNA cleavage studies on pUC18 DNA
      revealed compound 1 to preferentially bind in the minor groove and to covalently
      react with AT-rich sequences, particularly at the underlined adenine-N3 group of
      5'-AAAAA(865)-3'. This sequence specificity is similar to adozelesin and CC-1065.
      Using a 4-day continuous exposure, compound 1 inhibited the growth of K562 human
      chronic myeloid leukemia cells in culture. Compound 1 has appreciable
      cytotoxicity (IC50 value of 1.30 microM) relative to compound 2 (0.15 microM),
      the corresponding racemic and hydroxy-seco-CI-TMI analog. These results indicate
      that the aminophenethyl chloride group present in compound 1 has similar sequence
      specific and cytotoxic properties to the hydroxy-containing seco-precursors of CC
      1065 and the duocarmycins. Moreover, the results suggest that the chiral center
      present in the natural products is not absolutely necessary for biological
      activity. The novel aminophenethyl halide moiety is, therefore, a useful template
      from which to develop future achiral analogs of CC-1065 and the duocarmycins.

PMID- 16789883
TI  - Influence of trishomocubanes on sigma receptor binding of N-(1-benzyl-piperidin-4
      yl)-4-[123I]iodobenzamide in vivo in the rat brain.
AB  - Three new trishomocubane analogues based on the 4
      azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)] dodecane-3-ol skeleton have
      been synthesised and assessed for their affinities at both sigma-1 and sigma-2
      receptors. The effect of various N-substitution on the polycyclic moiety was
      examined. All synthesised compounds displayed high affinity for sigma-1 receptors
      (9-10 nM) and good affinity for sigma-2 receptors (230-310 nM), suggesting that
      substitution at the nitrogen moiety of the trishomocubane is well tolerated and
      represents a platform for the development of improved higher affinity sigma
      receptor ligands. The interaction of these functionalised trishomocubanes on the
      binding of the known sigma receptor radioligand, 4-[123I]IBP, was evaluated in
      the rat brain. Although 4-[123I]IBP had been used for imaging sigma receptors in
      tumours, this is the first examination of sigma receptor binding in the rat brain
      and therefore the potential of 4-[123I]IBP for imaging the brain was also
      evaluated. In vivo specificity and selectivity of 4-[123I]IBP binding was
      examined by studying the effects of pre-administration of sigma receptor binding
      drugs (+)-pentazocine and unlabelled 4-IBP. This resulted in a blockade of only
      42% of 4-[123I]IBP uptake in the brain indicating high degree of non-specific
      binding suggesting that it may not be suitable for imaging sigma receptors in the
      brain. The inhibition of 4-[123I]IBP uptake using the two of the three
      trishomocubanes displayed a consistent blockade of 48-30% in all brain
      structures. This demonstrates for the first time the ability of functionalised
      trishomocubanes to interact with sigma receptors in vivo.

PMID- 16789884
TI  - A new nucleotide-composition based fingerprint of SARS-CoV with visualization
      analysis.
AB  - It has been observed by conducting an extensive analysis of the two-dimensional
      cellular automata images of known SARS-CoV genome sequences that the V-shaped
      cross-lines only exist in some special locations, and hence can be used as a
      fingerprint to identify the SARS sequences. Such a discovery can be used to
      rapidly and reliably diagnose SARS coronavirus for both basic research in
      laboratories and practical application in clinics.

PMID- 16789885
TI  - Apoptosis signaling pathways in lung diseases.
AB  - Evidence that apoptosis plays an important role in the pathophysiology of lung
      diseases has been accumulated. Apoptosis signaling is classically composed of two
      principle pathways. One is a direct pathway from death receptor ligation to
      caspase cascade activation and cell death. Death receptor ligation triggers
      recruitment of the precursor form of caspase-8 to a death-inducing complex,
      through the adaptor protein FADD, which leads to caspase-8 activation. The other
      pathway triggered by stimuli such as drugs, radiation, infectious agents and
      reactive oxygen species is initiated in mitochondria. After cytochrome c is
      released into the cytosol from the mitochondria, it binds to Apaf1 and ATP, which
      then activate caspase-9. Recently, endoplasmic reticulum has also been shown to
      be the organelle to execute apoptosis. Further understanding of molecular
      mechanisms of apoptosis and its regulation by novel drugs may lead to the
      development of effective strategies against lung diseases. We overview the
      signaling pathways of apoptosis and discuss the involvement of apoptosis in the
      pathophysiology of various lung diseases.

PMID- 16789886
TI  - Full length and delta lactoferrin display differential cell localization
      dynamics, but do not act as tumor markers or significantly affect the expression
      of other genes.
AB  - Lactoferrin is a secreted protein related to transferrin. Lactoferrin indirectly
      protects host cells against foreign insults by killing bacteria, scavenging free
      iron, and binding to receptors required for viral invasion. However, lactoferrin
      is also proposed to act directly on cells as a transcription factor and tumor
      suppressor gene. In addition to full length lactoferrin, a truncated form, called
      delta lactoferrin, can also be produced by alternative splicing. We show here
      that transformed and nontransformed cells are equally able to express both full
      length and delta lactoferrin. Moreover, both forms of lactoferrin failed to
      substantially modulate the expression of other genes. Thus, lactoferrin does not
      seem to directly control gene expression or inhibit tumor cell growth.

PMID- 16789887
TI  - Cytotoxicity of an ebulin l-anti-human CD105 immunotoxin on mouse fibroblasts
      (L929) and rat myoblasts (L6E9) cells expressing human CD105.
AB  - Tumour growth is characterised by the formation of a fine vessel network or
      neovasculature which nourishes tumour cells. Two kinds of novel anti-angiogenic
      therapies are based on the prevention of vessels growth and on the destruction of
      those vessels already formed. We report here on the design and construction of a
      novel immunotoxin formed with the non-toxic type II ribosome-inactivating protein
      ebulin l and the mouse anti-human CD105 monoclonal antibody 44G4. The 44G4-ebulin
      immunotoxin was formed by covalent linking of both proteins with N-succinimidyl-3
      (2-pyridyldithio)propionate (SPDP) and was purified by chromatography on Superdex
      200 HiLoad. The analysis of the anti-ribosomal effects in a cell-free translation
      system indicated that conjugation does not affect the activity of ebulin l. The
      immunotoxin displays cytotoxicity with nanomolar IC50 values on human CD105+
      cells like the mouse fibroblasts L929 cells transfected with the short form of
      human CD105 and the rat myoblasts L6E9 transfected with the long form of human
      CD105. In contrast, cells lacking human CD105 were 2-2.5 logs less sensitive to
      the immunotoxin. Free ebulin displays IC50 values in the range 10(-6) M. Since
      CD105 is being considered as a potential target for the anti-vascular therapy of
      tumours, the present immunotoxin could be a promising tool for the anticancer
      therapy, especially due to the very low in vivo toxicity of ebulin l as compared
      ricin and other toxins used for immunotoxins.

PMID- 16789888
TI  - Protease inhibitors in the clinic.
AB  - This review describes the clinical status (based on available information) of
      experimental drugs that inhibit enzymes called proteases, or more precisely a sub
      class of proteases called peptidases that catalyse the hydrolysis of polypeptide
      main chain amide bonds. These peptidases are classified by the key catalytic
      residue in the active site of the enzyme that effects hydrolysis, namely
      aspartic, serine, cysteine, metallo or threonine proteases. In this review we
      show structures for 108 inhibitors of these enzymes and update the clinical
      disposition of over 100 inhibitors that have been considered worthy enough by
      pharmaceutical, biotechnology or academic researchers and their financial backers
      to be trialed in humans as prospective medicines. We outline some of their
      chemical and pharmacological characteristics and compare the current status of
      protease inhibitors in the clinic with what was observed about 5 years ago (Leung
      et al, J. Med. Chem. 2000, 43, 305-341). We assess the progress of protease
      inhibitors into man, predict their futures, and outline some of the hurdles that
      have been overcome and that still remain for this promising class of new
      therapeutic agents.

PMID- 16789889
TI  - Modelling of aldose reductase inhibitory activity of pyrrol-1-yl-acetic acid
      derivatives by means of multivariate statistics.
AB  - The inhibition of the aldose reductase enzyme (AR) is considered to be a
      promising approach to control chronic diabetes complications as well as a number
      of other pathological conditions. Thus considerable efforts are devoted to the
      development of aldose reductase inhibitors (ARIs) as possible pharmacotherapeutic
      agents. The establishment of adequate QSAR models would serve to this purpose. In
      the present study multivariate statistics was applied in order to analyse the AR
      inhibitory activity data of twenty three pyrrol-1-yl-acetic acid derivatives on
      the basis of essential molecular descriptors. The compounds contain one or two
      carbonyl keto groups, which serve as a bridge to link the pyrrole moiety to
      aromatic nuclei with or without further substitution. An adequate one component
      model with satisfactory statistics was obtained and validated for its robustness
      and predictive ability. The influence of the different descriptors in ARI
      activity is discussed. The derived model was further used to predict the activity
      of four independent compounds and the contribution of their specific structural
      characteristics in ARI activity was evaluated.

PMID- 16789890
TI  - Bangladeshi medicinal plant extracts inhibiting molecular interactions between
      nuclear factors and target DNA sequences mimicking NF-kappaB binding sites.
AB  - Several medicinal plants can be employed to produce extracts exhibiting
      biological effects. The aim of this work was to verify the ability of extracts
      derived from different medicinal plants of Bangladesh in interfering with
      specific DNA-protein interactions. The rationale for this study is based on the
      observation that alteration of gene transcription represents a very promising
      approach to control the expression of selected genes and could be obtained using
      different molecules acting on the interactions between DNA and transcription
      factors (TFs). We have analysed the antiproliferative activity of extracts from
      the medicinal plants Hemidesmus indicus, Polyalthia longifolia, Aphanamixis
      polystachya, Moringa oleifera, Lagerstroemia speciosa, Paederia foetida, Cassia
      sophera, Hygrophila auriculata and Ocimum sanctum. Antiproliferative activity was
      assayed on different human cell lines, including erythroleukemia K562, B-lymphoid
      Raji, T-lymphoid Jurkat and erythroleukemia HEL cell lines. We employed the
      electrophoretic mobility shift assay (EMSA) as a suitable technique for the
      identification of plant extracts altering the binding between transcription
      factors and the specific DNA elements. We found that low concentrations of
      Hemidesmus indicus, Polyalthia longifolia, Moringa oleifera and Lagerstroemia
      speciosa, and very low concentrations of Aphanamixis polystachya extracts inhibit
      the interactions between nuclear factors and target DNA elements mimicking
      sequences recognized by the nuclear factor kappaB (NF-kappaB). On the contrary,
      high amount of extracts from Paederia foetida, Cassia sophera, Hygrophila
      auriculata or Ocimum sanctum were unable to inhibit NF-kappaB/DNA interactions.
      Extracts inhibiting both NF-kappaB binding activity and tumor cell growth might
      be a source for anti-tumor compounds, while extracts inhibiting NF-kappaB/DNA
      interactions with lower effects on cell growth, could be of interest in the
      search of compounds active in inflammatory diseases, for which inhibition of NF
      kappaB binding activity without toxic effects should be obtained.

PMID- 16789891
TI  - Synthesis, structure-activity relationships and antagonistic effects in human MCF
      7 breast cancer cells of flexible estrogen receptor modulators.
AB  - Estrogen receptors are therapeutic intervention targets for diseases such as
      osteoporosis and breast cancer with both tamoxifen and raloxifene established as
      clinical estrogen receptor antagonists. We report a series of novel selective
      estrogen receptor modulators (SERMs) whose structures are based on a flexible
      core scaffold differing from the triphenylethylene of tamoxifen analogues through
      the insertion of a benzylic methylene group as a flexible spacer between the aryl
      ring C and the ethylene group. A facile synthesis of the target compounds
      utilises the titanium tetrachloride/zinc mediated McMurry coupling reaction.
      Successive introduction onto the parent scaffold of hydroxyl functional groups
      afforded a series of increased potency ligands for the ER - essentially exploring
      the predicted in vivo metabolic activation of such aromatic SERM ligands. This
      second generation compound series demonstrated high antiproliferative potency
      against the MCF-7 human breast cancer cell line, with low cytotoxicity. High ER
      binding affinity (IC50 20 nM) together with up to 12 fold ERalpha/beta
      selectivity was also observed. In addition, the compounds displayed
      antiestrogenic effects at 40 nM when evaluated in the Ishikawa cell line with
      little estrogenic stimulation. Representative ligands were shown to be pro
      apoptotic in human MCF-7 cells in a FACS based assay. Comparison of the docked
      structure obtained for the most active compound with the X-ray crystal structure
      reported for the complex of ERalpha and 4-hydroxytamoxifen, predict that these
      ligands bind in an antiestrogenic manner with some differences being observed in
      the benzylic Ring C orientation, as expected. This work further demonstrates the
      tolerance of the estrogen receptor towards flexible modulators.

PMID- 16789892
TI  - Computational insight into anti-mutagenic properties of CYP1A flavonoid ligands.
AB  - Cytochrome P450 1A (CYP1A) is a subclass of enzymes involved in the
      biotransformation of heterocyclic amines present in cooked red meat to
      carcinogenic compounds. Anti-cancer properties have long been associated with
      flavonoids, and some compounds of this class have been shown to interact directly
      with CYP1A2. The understanding of this interaction is the purpose of this work.
      As the number of experimentally tested molecules is limited, two complementary
      methods in terms of information provided, are proposed for the study of protein
      inhibitor interaction as alternatives to a QSAR analysis, using quantum mechanics
      as well as molecular mechanics.

PMID- 16789893
TI  - New non-peptidic inhibitors of papain derived from etacrynic acid.
AB  - Cysteine proteases are connected to various viral and parasitic infections, as
      well as to other severe diseases like arthritis, stroke and cancer. Due to its
      alpha,beta-unsaturated carbonyl moiety etacrynic acid, a well known diuretic, can
      inhibit cysteine proteases in a Michael-type reaction by reaction with the
      nucleophilic cysteine residue of the active site. For first structure-activity
      relationship studies modifications at various positions of the etacrynic acid
      structure have been investigated concerning inhibition potency against the CAC1
      protease papain: length of the side chain, substitution pattern of the aromatic
      ring as well as influence and necessity of acidic groups, esters or amides.
      Additionally, the effect of the aromatic ring was evaluated by replacement with a
      cyclohexyl moiety.

PMID- 16789894
TI  - QSAR of the anticonvulsant enaminones; molecular modeling aspects and other
      assessments.
AB  - The enaminones represent potentially useful agents for the clinical treatment in
      generalized tonic-clonic seizures (Epilepsia, 1993, 34(6), 1141-1145, Biopharm.
      Drug Disp. 2003, 397-407). A regression analysis was performed to provide a
      quantitative structure-activity relationship (QSAR) correlation model for
      prediction of activity for the anticonvulsant enaminones. Molecular modeling was
      performed to determine the molecular confluence of the Unverferth model (J. Med.
      Chem. 1998, 41, 63-73) to the enaminones. Conclusions related to the sodium
      channel model were assessed.

PMID- 16789895
TI  - Topoisomerase enzymes as therapeutic targets for cancer chemotherapy.
AB  - The topoisomerase enzymes are essential for DNA metabolism, where they act to
      adjust the number of supercoils in DNA, a key requirement in the cellular
      processes of transcription and replication. Their enzymatic mechanism creates
      transient nicks (type I) or breaks (type II) in the double stranded DNA polymer,
      allowing DNA to be converted between topological isomers. Humans possess both
      types of topoisomerase enzymes, however the two types utilize very different
      enzymatic mechanisms. Both type I and type II topoisomerases have been identified
      as clinically important targets for cancer chemotherapy and their inhibitors are
      central components in many therapeutic regimes. Over the course of the last 30
      years inhibitors with extensive structural diversity have been developed through
      a combination of drug screening and rational design programs. Simultaneously much
      emphasis has been placed upon establishing the mechanisms of action of both
      classes of topoisomerase enzyme. Crucial structural insights have come from the
      crystal structure of topoisomerase I, while modelling comparisons are beginning
      to map out a possible framework for topoisomerase II action. This review
      discusses these recent advances in the fields of enzyme mechanism and inhibitor
      design. We also address the development of drug resistance and dose-limiting side
      effects as well as cover alternative methods in drug delivery.

PMID- 16789896
TI  - Role of prostaglandin E receptor subtypes in gastroduodenal HCO3- secretion.
AB  - Gastroduodenal HCO3- secretion is a key process that aids in preventing acid
      peptic injury. Endogenous prostaglandins (PGs) play a particularly important role
      in the local control of this secretion. The secretion of HCO3- in both the
      stomach and duodenum was increased in response to PGE2 as well as mucosal
      acidification, the latter occurring with concomitant enhancement of mucosal PG
      generation. These HCO3- responses in the duodenum were markedly reduced by prior
      administration of the EP4 antagonist in rats, and profoundly decreased in the
      animals lacking EP3 receptors but not EP1 receptors. In contrast, gastric HCO3-
      responses induced by PGE2 and mucosal acidification were prevented by the EP1
      antagonist and disappeared in EP1, but not EP3-knockout mice. Consistent with
      these findings, duodenal HCO3- secretion was stimulated by both EP3 and EP4
      agonists but not EP1 or EP2 agonists, while gastric HCO3- secretion was increased
      by the EP1 agonist but not EP2, EP3 or EP4 agonists. In addition, the HCO3-
      stimulatory action of sulprostone (EP1/EP3 agonist) in the stomach was inhibited
      by the Ca2+ antagonist verapamil but not affected by IBMX, the inhibitor of
      phosphodiesterase, while that in the duodenum was inhibited by verapamil and
      enhanced by IBMX. Forskolin, the stimulator of adenylate cyclase, increased HCO3-
      secretion in the duodenum but not the stomach. Thus, the HCO3- stimulatory action
      of PGE2 in the duodenum is mediated by both EP3 and EP4 receptors being coupled
      intracellularly with both Ca2+ and cAMP, while that in the stomach is mediated by
      EP1 receptors, coupled with Ca2+.

PMID- 16789897
TI  - GPCR agonists and antagonists in the clinic.
AB  - This review describes current and new therapeutic agonists and antagonists of G
      protein-coupled receptors (GPCRs) currently used in the clinic. GPCRs are
      classified under the GRAFS system (Glutamate, Rhodopsin, Adhesion,
      Frizzled/taste2 and Secretin), with therapies having been developed for about 30
      GPCRs from the glutamate, rhodopsin and secretin families. Most of these
      therapies target the biogenic amine receptors of the rhodopsin family. Advancing
      technology has assisted in the identification of an increasing number of GPCRs,
      as well as contributing to the understanding of function and potential as
      pharmaceutical targets. With this has come the development of new therapies that
      target specific GPCRs, including peptide activated GPCRs. Where possible,
      agonists and antagonists are described individually, focusing on new therapies
      and their corresponding target receptors. However, the large number of reported
      biogenic amine therapies precludes, discussion of individual compounds and
      instead, they are discussed in relation to the receptor pharmacophore. Despite
      the large number of significant physiological responses known to be mediated by
      GPCRs, only about 4% of known GPCRs are currently targeted by therapeutics. This
      provides a great number of promising new targets for pharmaceutical development.

PMID- 16789899
TI  - Proteomic and computational methods in systems modeling of cellular signaling.
AB  - Cellular signaling lies at the core of cellular behavior, and is central for the
      understanding of many pathologic conditions. To comprehend how signal
      transduction is orchestrated at the molecular level remains the ultimate
      challenge for cell biology. In the last years there has been a revolution in the
      development of high-throughput methodologies in proteomics and genomics, which
      have provided extensive knowledge about expression profiles and molecular
      interaction-networks. However, these methods have typically provided qualitative
      and static information. This is about to turn, and several high-throughput
      methods are now available that provide quantitative and temporal information.
      These data are well suited for analysis by computational methods and
      bioinformatics, which are becoming increasingly valuable tools to grasp the
      complexity of cellular networks. At present, several cellular pathways have been
      modeled in silico and the analysis provides new understanding of the underlying
      properties that contribute to their dynamic features. Here, we review
      methodologies that are used for in silico modeling as well as methods to obtain
      large-scale quantitative data, and discuss how they can be integrated to generate
      powerful and predictive models of cellular processes. We argue that the
      generation of such models provide powerful tools to understand how systems
      properties emerges in healthy and pathologic states, and to generate efficient
      strategies for pharmacological intervention.

PMID- 16789900
TI  - Proteomic-based biomarker discovery with emphasis on cerebrospinal fluid and
      multiple sclerosis.
AB  - Discovery of disease specific biomarkers in human body fluids has become an
      important challenge in clinical proteomics. Facing the increasing threat of
      degenerative and disabling diseases like cancer, cardiovascular, neurological and
      inflammatory diseases in large parts of the world's population, there is an
      urgent need to improve early diagnostics. In this review we discuss possibilities
      and limitations connected to using mass spectrometry based proteomics in the
      search for novel biomarkers, with focus on multiple sclerosis as a typical
      representative for the large group of non-curable degenerative and disabling
      disease with the lack of specific tests for early diagnosis. Careful control of
      the pre-analytical phase including sampling, storage and fractionation of
      samples, in addition to a thoroughly considered patient selection, is important
      in order to avoid false biomarkers to appear in the resulting mass spectra.
      Furthermore, advanced computational tools are needed in order to discover
      potential biomarkers from the enormous data amounts generated by the mass
      spectrometers. The development of such computer tools is a research field
      currently in the start phase and could prove to be a bottle neck in the biomarker
      discovery the next years. Therefore, a rather detailed review of the most used
      computational and pre-analytical methods is given in this review. Mass
      spectrometry based biomarker discovery is undoubtedly still in its early infancy.
      However, in light of the potential of this technology to provide deep coverage of
      the body fluid proteomes, it will certainly consolidate its role in developing
      molecular medicine into clinical practice.

PMID- 16789901
TI  - Proteomic strategies for individualizing therapy of acute myeloid leukemia (AML).
AB  - Acute myeloid leukemia (AML) is an aggressive hematological malignancy
      characterized by accumulating myeloid precursor cells in the bone marrow, with
      approximately 2-3 months 50% survival if left untreated. With current treatment
      modalities the five years overall survival hardly exceeds 50%. Cytogenetics and
      molecular diagnostics guide the clinician to select individualized therapy in
      certain subsets of AML, achieving long-term survival above 70% of these cases.
      However, approximately half of the AML patients have no risk stratifying
      features, and early reports indicate that proteomic approaches may be utilized
      for disease classification as well as development of novel biomarkers related to
      prognosis, diagnosis, and choice of therapeutic regimen. Proteomics, here defined
      as the analysis of all proteins in a cell, in a cell compartment or in a
      signaling pathway, has probably its greatest potential in investigating pathways
      that are easily targeted by small molecules or therapeutic antibodies. The major
      methodological challenges include detection sensitivity in a limited clinical
      material, a problem that in some cases can be solved through designated
      multiplexed protein assays based on single cells or cell extracts. In this review
      we will discuss pharmacoproteomic studies of drugs regulating leukemia specific
      targets like all-trans retinoic acid, histone deacetylase inhibitors, proteasome
      inhibitors and tyrosine kinase inhibitors, as well as studies on drug resistance
      and graft-versus-host studies during stem cell transplantations. These studies
      indicate new avenues in AML diagnostics, individualized therapy design and
      therapy response surveillance for the clinician.

PMID- 16789902
TI  - Diagnostics, prognostic and therapeutic exploitation of telomeres and telomerase
      in leukemias.
AB  - Telomeres are specialized structures at the end of human chromosomes. Telomere
      length decreases with each cell division, thus, reflecting the mitotic history of
      somatic cells. Telomerase, the ribonucleoprotein enzyme which maintains telomeres
      of eukaryotic chromosomes, is up-regulated in the vast majority of human
      neoplasia but not in normal somatic tissues. In contrast to other somatic cells,
      normal primitive human hematopoietic cells and some peripheral blood cells
      expressed low levels of telomerase activity. This activity is thought to play an
      important role in self-renewal of hematopoietic stem cells. In malignant
      disorders, telomere lengths are generally shortened and telomerase expression and
      activity enhanced with high differences in the levels. Although it is necessary
      to be cautious in interpreting these data, there are indications that telomere
      length and telomerase expression and activity can serve as a molecular marker of
      the clinical progression and prognosis of most leukemias. Approaches that
      directly target telomerase, telomeres or telomerase regulatory mechanisms have
      been developed. Some of these anti-telomerase strategies in combination with
      conventional drugs proved to be promising in some types of leukemias.

PMID- 16789903
TI  - Proteomics approaches to elucidate oncogenic tyrosine kinase signaling in myeloid
      malignancies.
AB  - Myeloid malignancies frequently harbor specific mutations in protein tyrosine
      kinases leading to oncogenic cell signaling. The most extensively investigated
      example is chronic myeloid leukemia, where the pathogenic tyrosine kinase fusion
      protein Bcr-Abl is a successful target for disease control by the specific
      inhibitor imatinib mesylate. In acute myeloid leukemia the receptor tyrosine
      kinase Flt3 is frequently mutated and inhibitors to impair the oncogenic
      signaling are in development. In this review we exemplify oncogenic signaling and
      how signal pathways can be unraveled with help from proteomics-based
      technologies. The distinction between cell extract and single cell approaches
      aiming at rigorous standardization and reliable quantitative aspects for future
      proteomics-based diagnostics is discussed.

PMID- 16789904
TI  - Proteomics of p53 in diagnostics and therapy of acute myeloid leukemia.
AB  - The anti-oncogene TP53 is frequently mutated in human cancer, but in
      hematological malignancies this is a rare feature. In acute myeloid leukemia
      (AML) more than 90% of the patients comprise wild type TP53 in their cancer
      cells, but if TP53 is mutated or deleted the disease is often found to be
      chemoresistant. In this review we define proteomics of the oncogene product p53
      as the study of proteins in the p53 regulating signaling networks, as well as the
      protein study of members of the p53 family itself. Various messenger RNA splice
      forms as well as a multitude of post-translational modifications give a high
      number of protein isoforms in the p53 family. Some of the proteomic techniques
      allow detection of various isoforms, such as two-dimensional gel electrophoresis
      in combination with tandem mass spectrometry (MS/MS) and this methodology may
      therefore increasingly be used as a diagnostic tool in human disease. We
      introduce the p53 protein as an illustration of the complexity of post
      translational modifications that may affect one highly connected protein and
      discuss the possible impact in AML diagnostics if the p53 profile is reflecting
      cell stress and status of signal transduction systems of the malignancy.

PMID- 16789905
TI  - Algal toxins as guidance to identify phosphoproteins with key roles in apoptotic
      cell death.
AB  - The protein phosphatase inhibiting toxins microcystin and nodularin act rapidly
      to induce apoptotic cell death. Their inhibitory effect on protein phosphatases 1
      and 2A can be utilized as tools to understand the phosphorylation-dependent
      regulatory mechanism underlying the early stage of apoptosis. The incubation of
      freshly isolated hepatocytes with these toxins results in a rapid
      hyperphosphorylation of cellular proteins before any morphological signs of
      apoptosis appears [Fladmark, K. E., Brustugun, O. T., Hovland, R., Boe, R.,
      Gjertsen, B. T., Zhivotovsky, B. and Doskeland, S. O. (1999) Cell Death Differ.
      6, 1099-108]. Proteins subjected to phosphorylation in this early phase of
      apoptosis may play key roles in this cellular process and become valuable targets
      for drug development. The ultra-rapid apoptosis-induction by microcystin and
      nodularin provides a unique amount of synchronized apoptotic cells with "large"
      amounts of mainly serine/threonine phosphorylated proteins. This ultra-rapid
      toxin-induced up-concentration of phosphorylated proteins reduces the material
      needed as well as simplifies our effort in order to obtain enough phosphoproteins
      for mass spectrometric identification and characterization. We will here give an
      overview of our strategy for identification of low-abundance phosphoproteins
      involved in algal toxin-induced apoptosis and most likely also in a general
      apoptotic pathway.

PMID- 16789906
TI  - Does isoform diversity explain functional differences in the 14-3-3 protein
      family?
AB  - The 14-3-3 family of proteins was originally identified in 1967 as simply an
      abundant brain protein. However it took almost 25 years before the ubiquitous
      role of 14-3-3 in cell biology was recognized when it was found to interact with
      several signalling and proto-oncogene proteins. Subsequently 14-3-3 proteins were
      the first protein recognized to bind a discrete phosphoserine/threonine-binding
      motifs. In mammals the 14-3-3 protein family is comprised of seven homologous
      isoforms. The 14-3-3 family members are expressed in all eukaryotes and although
      no single conserved function of the 14-3-3s is apparent, their ability to bind
      other proteins seems a crucial characteristic. To date more than 300 binding
      partners have been identified, of which most are phosphoproteins. Consequently,
      it has become clear that 14-3-3 proteins are involved in the regulation of most
      cellular processes, including several metabolic pathways, redox-regulation,
      transcription, RNA processing, protein synthesis, protein folding and
      degradation, cell cycle, cytoskeletal organization and cellular trafficking. In
      this review we include recent reports on the regulation of 14-3-3 by
      phosphorylation, and discuss the possible functional significance of the
      existence of distinct 14-3-3 isoforms in light of recent proteomics studies. In
      addition we discuss 14-3-3 interaction as a possible drug target.

PMID- 16789908
TI  - In silico discrimination of single nucleotide polymorphisms and pathological
      mutations in human gene promoter regions by means of local DNA sequence context
      and regularity.
AB  - DNA sequence features were sought that could be used for the in silico
      ascertainment of the likely functional consequences of single nucleotide changes
      in human gene promoter regions. To identify relevant features of the local DNA
      sequence context, we transformed into consensus tables the nucleotide composition
      of sequences flanking 101 promoter SNPs of type C<-->T or A<-->G, defined
      empirically as being either 'functional' or 'non-functional' on the basis of a
      standardised reporter gene assay. The similarity of a given sequence to these
      consensus tables was then measured by means of the Shapiro-Senapathy score. A
      decision rule with the potential to discriminate between empirically ascertained
      functional and non-functional SNPs was proposed that potentiated discrimination
      between functional and non-functional SNPs with a sensitivity of 80% and a
      specificity of 20%. Two further datasets (viz. disease-associated SNPs of types
      A<-->G and C<-->T (N = 75) and pathological promoter mutations (transitions, N =
      114)) were retrieved from the Human Gene Mutation Database (HGMD;
      http://www.hgmd.org/) and analyzed using consensus tables derived from the
      functional and non-functional promoter SNPs; approximately 70% were correctly
      recognized as being of probable functional significance. Complexity analysis was
      also used to quantify the regularity of the local DNA sequence environment.
      Functional SNPs/mutations of type C<-->T were found to occur in DNA regions
      characterized by lower average sequence complexity as measured with respect to
      symmetric elements; complexity values increased gradually from functional SNPs
      and pathological mutations to functional disease-associated SNPs and non
      functional SNPs. This may reflect the internal axial symmetry that frequently
      characterizes transcription factor binding sites.

PMID- 16789907
TI  - pEg6, a spire family member, is a maternal gene encoding a vegetally localized
      mRNA in Xenopus embryos.
AB  - BACKGROUND INFORMATION: In Xenopus, during oocyte maturation and the segmentation
      period, cell cycle progression is independent of new transcription, but requires
      de novo translation. This suggests that the completion of oocyte maturation and
      then the rapid cell division period is controlled exclusively at a post
      transcriptional level by specific gene products. To isolate these maternal genes,
      a differential screening of a Xenopus egg cDNA library was performed. Several
      cDNAs were isolated which correspond to mRNA polyadenylated in eggs and
      deadenylated in embryos, and these constitute the founders members of the Eg
      family of mRNAs. RESULTS: We report here the characterization of Eg6 mRNA as a
      novel maternal gene expressed in Xenopus egg until gastrula stage. The Eg6
      transcript is initially concentrated in the vegetal cytoplasm of the egg, and
      later the distribution of the transcript marks the posterior vegetal end of
      developing embryos. pEg6 is a multidomain protein with a kinase non-catalytic C
      lobe domain of unknown function, a cluster of four WH2 (Wiskott-Aldrich syndrome
      protein homology 2) domains and a modified FYVE zinc-finger motif. The amino acid
      sequence of pEg6 is related to PEM-5 (posterior end mark-5), from an ascidian
      maternal mRNA, and spire, a Drosophila protein required to establish dorsal
      ventral and anterior-posterior axes of polarity and recently described as an
      actin nucleation factor. In Xenopus and Schizosaccharomyces pombe cells pEg6
      expression induces filamentous actin clusters and is associated with vesicular
      structure. CONCLUSION: These data suggest that pEg6 acts as a vegetally localized
      factor contributing to the actin nucleation process during Xenopus early
      development.

PMID- 16789910
TI  - Gauss-function-Based model of hydrophobicity density in proteins.
AB  - The model adopting the three-dimensional Gauss function to express the
      hydrophobicity distribution in proteins is presented in this paper. The tendency
      to create the hydrophobic center during protein folding is expressed in form of
      an external force field of the form of three-dimensional Gauss function which
      directs the folding polypeptide to locate the hydrophobic residues in a central
      part of the molecule and hydrophilic ones exposed toward the molecular surface.
      The decrease of the differences between hydrophobicity distribution as it appears
      at each step of the folding simulation and the expected hydrophobicity
      distribution (three-dimensional Gauss function) is the convergence criterion
      together with traditional non-bonding interaction optimization. The model was
      applied to fold the hypothetical membrane protein (target protein in CASP6)
      TA0354_69_121 from Thermoplasma acidophilum.

PMID- 16789909
TI  - Simulation-based validation of the p53 transcriptional activity with hybrid
      functional petri net.
AB  - MDM2 and p19ARF are essential proteins in cancer pathways forming a complex with
      protein p53 to control the transcriptional activity of protein p53. It is
      confirmed that protein p53 loses its transcriptional activity by forming the
      functional dimer with protein MDM2. However, it is still unclear that protein p53
      keeps its transcriptional activity when it forms the trimer with proteins MDM2
      and p19ARF. We have observed mutual behaviors among genes p53, MDM2, p19ARF and
      their products on a computational model with hybrid functional Petri net (HFPN)
      which is constructed based on information described in the literature. The
      simulation results suggested that protein p53 should have the transcriptional
      activity in the forms of the trimer of proteins p53, MDM2, and p19ARE This paper
      also discusses the advantages of HFPN based modeling method in terms of pathway
      description for simulations.

PMID- 16789911
TI  - Hunting for insect-specific protein domains.
AB  - Automatically finding new protein domains is a challenge when using the complete
      collection of known proteins (i.e., UniProt). By limiting the taxonomic range to
      class insecta, including two full proteomes (A. gambiae and D. melanogaster), we
      reduced the size of the search space in the hope of finding taxon-specific
      domains. The MKDOM2 program
      (http://prodes.toulouse.inra.fr/prodom/xdom/mkdom2.html) was used to cluster the
      insect proteins into potential domains that were analyzed manually in a second
      step. We analyzed 219 potential domains, of which 2 were insect-specific. We show
      that it is possible to find new domains or to extend known domains using a semi
      automated method; however the goal to detect class-specific domains was only
      partially achieved in the sense that the new domains we found were not all insect
      specific domains. The files used as input and the resulting output files, as well
      as extensive descriptions of the domains, are available as supplementary data
      from http://bioinf.ibun.unal.edu.co/insecta/.

PMID- 16789912
TI  - In silico identification of potential therapeutic targets in the human pathogen
      Helicobacter pylori.
AB  - Availability of genome sequences of pathogens has provided a tremendous amount of
      information that can be useful in drug target and vaccine target identification.
      One of the recently adopted strategies is based on a subtractive genomics
      approach, in which the subtraction dataset between the host and pathogen genome
      provides information for a set of genes that are likely to be essential to the
      pathogen but absent in the host. This approach has been used successfully in
      recent times to identify essential genes in Pseudomonas aeruginosa. We have used
      the same methodology to analyse the whole genome sequence of the human gastric
      pathogen Helicobacter pylori. Our analysis revealed that out of the 1590 coding
      sequences of the pathogen, 40 represent essential genes that have no human
      homolog. We have further analysed these 40 genes by the protein sequence
      databases to list some 10 genes whose products are possibly exposed on the
      pathogen surface. This preliminary work reported here identifies a small subset
      of the Helicobacter proteome that might be investigated further for identifying
      potential drug and vaccine targets in this pathogen.

PMID- 16789913
TI  - GPAC: benchmarking the sensitivity of genome informatics analysis to genome
      annotation completeness.
AB  - In view of the recent explosion in genome sequence data, and the 200 or more
      complete genome sequences currently available, the importance of genome-scale
      bioinformatics analysis is increasing rapidly. However, computational genome
      informatics analyses often lack a statistical assessment of their sensitivity to
      the completeness of the functional annotation. Therefore, a pre-analysis method
      to automatically validate the sensitivity of computational genome analyses with
      regard to genome annotation completeness is useful for this purpose. In this
      report we developed the Gene Prediction Accuracy Classification (GPAC) test,
      which provides statistical evidence of sensitivity by repeating the same analysis
      for five different gene groups (classified according to annotation accuracy
      level), and for randomly sampled gene groups, with the same number of genes as
      each of the five classified groups. Variability in these results is then
      assessed, and if the results vary significantly with different data subsets, the
      analysis is considered "sensitive" to annotation completeness, and careful
      selection of data is advised prior to the actual in silico analysis. The GPAC
      test has been applied to the analyses of Sakai et al., 2001, and Ohno et al.,
      2001, and it revealed that the analysis of Ohno et al. was more sensitive to
      annotation completeness. It showed that GPAC could be employed to ascertain the
      sensitivity of an analysis. The GPAC bendhmarking software is freely available in
      the latest G-language Genome Analysis Environment package, at http://www.g
      language.org/.

PMID- 16789914
TI  - CorrXpression--identification of significant groups of genes and experiments by
      means of correspondence analysis and ratio analysis.
AB  - CorrXpression is a stand-alone desktop application for the identification of
      significant genes within collections of microarrays. The software combines three
      methods in two steps of analysis: correspondence analysis (CA), ratio analysis
      and correlation analysis. The graphical interface of CorrXpression visualizes the
      result of the CA with a biplot and the expression of selected genes in dependency
      of the experiments as bar diagrams. The CA-plot is an excellent tool for
      visualization and evaluation of data and results of ratio analysis and
      correlation analysis. The input data are selected from a database or from
      appropriate ASCII files.

PMID- 16789915
TI  - DNA motifs and sequence periodicities.
AB  - Genomic DNA sequences contain a wealth of information about the bendability and
      curvature of the DNA molecule. For example, the well-known 10-11 bp periodicities
      within genomes can be attributed to supercoiled structures or wrapping around
      nucleosomes. Such periodic signals have previously been examined mainly based on
      mono- or dinucleotide correlations. In this study, we generalize this approach
      and analyze correlation functions of longer motifs such as tetramers or poly(A)
      sequences. Periodically placed motifs may indicate regular protein binding or
      curvature signals. We detected various periodic signals e.g. strong 10-11 bp
      oscillations of periodically placed poly(A), poly(T) or poly(W) stretches. These
      observations lead to a new view on the intensively studied 10-11 bp
      periodicities.

PMID- 16789917
TI  - Analyzing stationary states of gene regulatory network using petri nets.
AB  - We introduce and formally define the notion of a stationary state for Petri nets.
      We also propose a fully automatic method for finding such states. The procedure
      makes use of the Presburger arithmetic to describe all the stationary states.
      Finally we apply this novel approach to find stationary states of a gene
      regulatory network describing the flower morphogenesis of A. thaliana. This shows
      that the proposed method can be successfully applied in the study of biological
      systems.

PMID- 16789916
TI  - Noise reduction from genotyping microarrays using probe level information.
AB  - Genomic copy number change is one of the important phenomenon observed in cancer
      and other genetic disorders. Recently oligonucleotide microarrays have been used
      to analyze changes in the copy number. Although high density microarrays provide
      genome wide useful data on copy number, they are often associated with
      substantial amount of experimental noise that could affect the performance of the
      analyses. We used the high density oligonucleotide genotyping microarrays in our
      experiments that uses redundant probe tiling approach for individual SNPs. We
      found that the noise in the genotyping microarray data is associated with several
      experimental steps during target preparation and devised an algorithm that takes
      into account those experimental parameters. Additionally, defective probes that
      do not hybridize well to the target and therefore could not be modified
      inherently were detected and omitted automatically by using the algorithm. When
      we applied the algorithm to actual datasets, we could reduce the noise
      substantially without compressing the dynamic range. Additionally, combinatorial
      use of our noise reduction algorithm and conventional breakpoint detection
      algorithm successfully detected a microamplification of c-myc which was
      overlooked in the raw data. The algorithm described here is freely available with
      the software upon request to all non-profit researchers.

PMID- 16789918
TI  - Prediction of C alpha-H...O and C alpha-H...pi interactions in proteins using
      recurrent neural network.
AB  - In this study, an attempt has been made to develop a method for predicting weak
      hydrogen bonding interactions, namely, C alpha-H...O and C alpha-H...pi
      interactions in proteins using artificial neural network. Both standard feed
      forward neural network (FNN) and recurrent neural networks (RNN) have been
      trained and tested using five-fold cross-validation on a non-homologous dataset
      of 2298 protein chains where no pair of sequences has more than 25% sequence
      identity. It has been found that the prediction accuracy varies with the
      separation distance between donor and acceptor residues. The maximum sensitivity
      achieved with RNN for C alpha-H...O is 51.2% when donor and acceptor residues are
      four residues apart (i.e. at delta D-A = 4) and for C alpha-H...pi is 82.1% at
      delta D-A = 3. The performance of RNN is increased by 1-3% for both types of
      interactions when PSIPRED predicted protein secondary structure is used. Overall,
      RNN performs better than feed-forward networks at all separation distances
      between donor-acceptor pair for both types of interactions. Based on the
      observations, a web server CHpredict (available at
      http://www.imtech.res.in/raghava/chpredict/) has been developed for predicting
      donor and acceptor residues in C alpha-H...O and C alpha-H...pi interactions in
      proteins.

PMID- 16789919
TI  - Social behavior of the yeast protein-protein interaction network.
AB  - Protein-protein interaction networks are useful in contextual annotation of
      protein function and in general to achieve a system-level understanding of
      cellular behavior. This work reports on the social behavior of the yeast protein
      protein interaction network and concludes that it is non-random. This work, while
      providing an analysis of organization of genes into functional societies, can
      potentially be useful in assessing the accuracy of contextual gene annotation
      based on such interaction networks.

PMID- 16789920
TI  - Analysis and prediction of helix shift errors in homology modeling.
AB  - High sequence identity between two proteins (e.g. > 60%) is a strong evidence for
      high structural similarity. However, internal shifts in one of the two proteins
      can sometimes give rise to unexpectedly high structural differences. This, in
      turn, causes unreliable structure predictions when two such proteins are used in
      homology modeling. Here, we perform a computational analysis of helix shifts and
      we show that their occurrence can be predicted with statistical learning methods.
      Our results indicate that helix shifts increase the RMS error by factor 2.6
      compared to those protein pairs without a helix shift. Although helix shifts are
      rare (1.6% of helices and a commensurately higher number of proteins are
      affected), they therefore pose a significant problem for reliable structure
      prediction systems. In this paper, we prototype a new approach for model quality
      assessment and demonstrate that it can successfully warn against helix shifts. A
      support vector machine trained on a wide range of sequence and structure
      properties predicts the occurrence of helix shifts with a sensitivity of 74.2%
      and a specificity of 83.6%. On an equalized test dataset, this corresponds to an
      accuracy of 78.9%. Projected to the full dataset, it translates to an accuracy of
      83.4%. Our analysis shows that helix shift detection is a valuable building block
      for highly reliable structure prediction systems. Furthermore, the statistical
      learning based approach to helix shift detection that we employ here is
      orthogonal to well-established model quality assessment methods (which use
      geometric constraint checking or mean force potentials). Therefore, a further
      increase of prediction accuracy is expected from the combination of these
      methods.

PMID- 16789922
TI  - Abstracts of the 27th Annual Scientific Meeting of the High Blood Pressure
      Research Council of Australia Inc. December 7-9, 2005. Melbourne, Australia.

PMID- 16789923
TI  - 5-hydroxytryptamine in the cardiovascular system: focus on the serotonin
      transporter (SERT).
AB  - 1. The function of the serotonin transporter (SERT) is to take up and release
      serotonin (5-hydroxytyptamine (5-HT)) from cells and this function of SERT in the
      central nervous system (CNS) is well-documented; SERT is the target of selective
      serotonin reuptake inhibitors used in the treatment of CNS disorders, such as
      depression. 2. The aim of the present review is to discuss our current knowledge
      of 5-HT and SERT in the cardiovascular (CV) system, as well as their function in
      physiological and pathophysiological states. 3. The SERT protein has been located
      in multiple CV tissues, including the heart, blood vessels, brain, platelets,
      adrenal gland and kidney. Modification of SERT function occurs at both
      transcriptional and translational levels. The functions of SERT in these tissues
      is largely unexplored, but includes modulation of cardiac and smooth muscle
      contractility, platelet aggregation, cellular mitogenesis, modulating neuronal
      activity and urinary excretion. 4. Recent studies have uncovered potential
      relationships between the expression of SERT gene promoter variants (long (l) or
      short (s)) with CV diseases. Specifically, the risk of myocardial infarction and
      pulmonary hypertension is increased with expression of the ll promoter, a variant
      associated with increased expression and function of SERT. The relationship
      between promoter variants and other CV diseases has not been investigated. 5.
      Newly available experimental tools, such as pharmacological compounds and
      genetically altered mice, should prove useful in the investigation of the
      function of SERT in the CV system. 6. In summary, the function of SERT in the CV
      system is just beginning to be revealed.

PMID- 16789924
TI  - Thermal preconditioning protects the human internal mammary artery from
      hypoxia/re-oxygenation-induced damage.
AB  - 1. Preconditioning has been demonstrated to ameliorate ischaemia/reperfusion
      injury in several cells and tissues. Therefore, in the present study we
      investigated whether preconditioning of human bypass grafts, internal mammary
      artery (IMA) and saphenous vein (SV) induces heat shock protein (Hsp) expression
      and reduces apoptosis in response to subsequent hypoxia/re-oxygenation damage in
      both vessels. 2. Internal mammary artery and SV rings, obtained from 30 patients
      (median age 66.5 years) undergoing coronary artery bypass grafting, were either
      incubated for 30 min at 42 degrees C (preconditioned) or kept in a standard
      incubator at 37 degrees C (not preconditioned). Six hours later, graft segments
      were exposed to 90 min hypoxia followed by a 30 min re-oxygenation period.
      Western blot, real-time quantative polymerase chain reaction analysis and
      apoptosis detection by the Terminal deoxyribonucleotidyl transferase-mediated
      dUTP-digoxigenin nick end-labelling method were performed. 3. Heat-preconditioned
      IMA showed significantly increased protein expression of Hsp72 after hypoxia/re
      oxygenation treatment compared with controls (median 9.1 vs 5.0 microg/mg total
      protein; P = 0.048). Expression of Hsp73 was weak and Hsp60 was not detectable in
      the IMA. 4. In the SV, neither protein nor mRNA expression of Hsp were
      significantly different between preconditioned and not preconditioned veins. 5.
      There were significantly fewer apoptotic cells in the intima of the
      preconditioned compared with not preconditioned IMA (P = 0.041) after hypoxia/re
      oxygenation injury, whereas in the SV apoptosis was not significantly prevented
      by preconditioning. 6. Mild heat preconditioning before hypoxia/re-oxygenation
      injury is a stimulus for Hsp72 protein expression and a reduction in apoptosis in
      the human IMA.

PMID- 16789925
TI  - Matching of sarcoplasmic reticulum and contractile properties in rat fast- and
      slow-twitch muscle fibres.
AB  - 1. The twitch characteristics (fast-twitch or slow-twitch) of skeletal muscle
      fibres are determined not only by the contractile apparatus properties of the
      fibre, but also by the time-course of Ca2+ release and re-uptake by the
      sarcoplasmic reticulum (SR). The present study examined, in individual fibres
      from non-transforming muscle of the rat, whether particular SR properties are
      matched to the contractile apparatus properties of the fibre, in particular in
      the case of fibres with fast-twitch contractile apparatus located in a slow
      twitch muscle, namely the soleus. 2. Force was recorded in single, mechanically
      skinned fibres from extensor digitorum longus (EDL), gastrocnemius, peroneus
      longus and soleus muscles. Using repeated cycles in which the SR was emptied of
      all releasable Ca2+ and then reloaded, it was possible to determine the relative
      amount of Ca2+ present in the SR endogenously, the maximum SR capacity and the
      rate of Ca2+ loading. The sensitivity of the contractile apparatus to Ca2+ and
      Sr2+ was used to classify the fibres as fast-twitch (FT), slow-twitch (ST) or
      mixed (< 3% of the fibres examined) and thereby identify the likely troponin C
      and myosin heavy chain types present. 3. There was no significant difference in
      SR properties between the groups of FT fibres obtained from the four different
      muscles, including soleus. Despite some overlap in the SR properties of
      individual fibres between the FT and ST groups, the properties of the FT fibres
      in all four muscles studied were significantly different from those of the ST and
      mixed fibres. 4. In general, in FT fibres the SR had a larger capacity and the
      endogenous Ca2+ content was a relatively lower percentage of maximum compared
      with ST fibres. Importantly, in terms of their SR properties, FT fibres from
      soleus muscle more closely resembled FT fibres from other muscles than they did
      ST fibres from soleus muscle.

PMID- 16789926
TI  - Anti-inflammatory and anti-nociceptive activity of risedronate in experimental
      pain models in rats and mice.
AB  - 1. The antinociceptive effect of risedronate in experimental pain models in rats
      and mice was investigated in the present study. 2. Rats received zymosan intra
      articularly (i.art.) into the right knee joint and the nociceptive response was
      assessed using the articular incapacitation test. Joint washouts were used for
      determining cell influx, tumour necrosis factor (TNF)-alpha and leukotriene (LT)
      B4 levels. 3. Mice received either zymosan (1 mg) or acetic acid (0.6%) i.p. and
      the nociceptive response was measured as the number of writhings between 0 and 30
      min after the stimuli. Control animals received i.p. injections of saline. 4.
      Groups were pretreated with risedronate (5-500 microg/kg, s.c.) and compared with
      vehicle (saline)-treated (NT) animals. One group of rats was cotreated with the
      micro-opioid receptor antagonist naloxone (2 mg/kg, s.c.) prior to risedronate,
      followed by 1 mg zymosan i.art. 5. Risedronate, at 100 and 500 microg/kg,
      significantly and dose-dependently inhibited the nociceptive response in the
      writhings test (P < 0.05), inhibiting responses to acetic acid by 65.4 and 49.2%,
      respectively, and to zymosan by 72.9 and 71.9%, respectively. 6. Pretreatment
      with risedronate also significantly (P < 0.05) and dose-dependently inhibited the
      articular incapacitation in zymosan-arthritis. 7. Risedronate, at 50 microg/kg,
      significantly inhibited TNF-alpha release as compared with the NT group (39.4 +/-
      9.8 vs 145.6 +/- 43.3 pg/mL TNF-alpha, respectively). 8. Risedronate, at 50 and
      100 microg/kg, significantly inhibited LTB4 release into the joints compared with
      the NT group (2883.1 +/- 73.2, 1911.5 +/- 205.3 and 4709.9 +/- 237.2 pg/mL,
      respectively). These effects of risedronate were associated with a significant
      reduction in the inflammatory cell infiltration. 9. Cotreatment with risedronate
      and naloxone did not reverse the antinociceptive effects of risedronate in
      zymosan-arthritis. 10. This is the first demonstration that risedronate displays
      intrinsic antihypernociceptive activity. This effect is associated with reduced
      cell infiltration and inhibition of TNF-alpha and LTB4 release and is not linked
      to an endogenous opioid-release mechanism.

PMID- 16789927
TI  - Arterial baroreflex is not involved in salt preference in rats.
AB  - 1. One unusual and interesting feature of spontaneously hypertensive rats (SHR)
      is their salt preference. This behaviour is known to be independent of blood
      pressure. 2. Arterial baroreflex (ABR) function is impaired in SHR. Therefore,
      the present study was designed to explore the relationship between ABR function
      and salt preference in rats. 3. Twenty-seven SHR, aged 11 months, were used.
      Blood pressure and baroreflex sensitivity (BRS) were determined in conscious,
      freely moving SHR after the measurement of salt preference. It was found that BRS
      did not relate to the salt preference in these rats. 4. Another group of
      normotensive Sprague-Dawley rats, aged 10 weeks, underwent either sinoaortic
      denervation (SAD) or sham operation. Salt preference was determined before and 4
      weeks after SAD. Sinoaortic denervation did not alter salt preference in
      normotensive rats. 5. It is concluded that ABR function does not influence the
      salt preference in rats.

PMID- 16789928
TI  - Antiviral effects of saikosaponins on human coronavirus 229E in vitro.
AB  - 1. Saikosaponins represent a group of oleanane derivatives, usually as
      glucosides, that are found in a number of plant families. Saikosaponins isolated
      from medicinal plants such as Bupleurum spp., Heteromorpha spp. and Scrophularia
      scorodonia have been reported to possess various biological activities,
      specifically antihepatitis, antinephritis, antihepatoma, anti-inflammation,
      immunomodulation and antibacterial effects. 2. The aim of the present study was
      to examine the anticoronaviral activity of saikosaponins (A, B2, C and D) and
      their mode of action. Using the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-5
      [(phenylamino) carbonyl-2H-tetrazolium hydroxide] (XTT) assay, results showed
      that all saikosaponins tested demonstrated antiviral activity at concentrations
      of 0.25-25 micromol/L, with the strongest activity being noted for saikosaponin
      B2 (IC50 = 1.7 +/- 0.1 micromol/L). Interestingly, both saikosaponins A (50%
      cellular cytotoxicity (CC50) concentration = 228.1 +/- 3.8 micromol/L;
      selectivity index (SI) = 26.6) and B2 (CC50 = 383.3 +/- 0.2 micromol/L; SI =
      221.9) exhibited no cytotoxic effects on target cells at concentrations that
      achieved antiviral activity. In the time-of-addition studies, saikosaponin B2, at
      6 micromol/L, significantly inhibited human coronavirus 229E infection following
      its addition at various time pre-infection (-4 to -1 h), coinfection (0 h) and
      post-infection (1-4 h). Furthermore, saikosaponin B2 also showed an inhibitory
      effect on viral attachment and penetration. 3. The present results indicate that
      saikosaponin B2 has potent anticoronaviral activity and that its mode of action
      possibly involves interference in the early stage of viral replication, such as
      absorption and penetration of the virus.

PMID- 16789929
TI  - Therapeutic angiogenesis by intramuscular injection of fibrin particles into
      ischaemic hindlimbs.
AB  - 1. Fibrin gel has been used as a carrier of angiogenic molecules to promote
      neovascularization in animal models of limb ischaemia. However, little is known
      about the effects of fibrin itself under such pathological conditions.
      Accordingly, the present study tested the efficacy of fibrin in a rabbit model of
      acute hindlimb ischaemia. 2. Unilateral ischaemia was induced by resection of the
      left femoral artery. Seven days after surgery, fibrin particles (FP), which were
      free of fibrinogen, thrombin and vascular endothelial growth factor, were
      injected directly into the ischaemic thigh muscles. Twenty-four rabbits were
      divided into four groups, namely a control group receiving phosphate-buffered
      saline and three FP-treated groups receiving 5, 10 or 20 mg FP. 3. Collateral
      vessel development and limb perfusion were assessed by angiography, measuring the
      calf blood pressure ratio (BPR), thermographic scanning and the histological
      determination of capillary density. 4. At day 35 post-surgery, the treatment with
      5 mg FP produced an augmentation of collateral vessel development (P < 0.01),
      increased numbers of capillaries (P < 0.05) and improved perfusion manifested by
      a higher blood flow (P < 0.01) and calf BPR (P < 0.05) compared with controls.
      Treatment with 10 and 20 mg FP had similar effects to those observed with 5 mg
      FP. 5. The present study reveals that FP promotes angiogenesis in a rabbit model
      of hindlimb ischaemia, thus providing a feasible approach to therapeutic
      angiogenesis in ischaemic diseases.

PMID- 16789930
TI  - Effect of low-voltage electrical stimulation on angiogenic growth factors in
      ischaemic rat skeletal muscle.
AB  - 1. Low-voltage electrical stimulation (LVES) in skeletal muscle at a level far
      below the threshold of muscle contraction has been reported to promote local
      angiogenesis. However, the mechanism underlying the promotion of local
      angiogenesis by LVES has not been fully elucidated. In the present study, we
      evaluated whether angiogenic factors, such as vascular endotherial growth factor
      (VEGF), hepatocyte growth factor (HGF) and fibroblast growth factor (FGF), as
      well as other disadvantageous factors, such as inflammation (interleukin (IL)-6)
      and hypoxia (hypoxia-inducible factor (HIF)-1alpha), contribute to the local
      angiogenesis produced by LVES. 2. We completely excised bilateral femoral
      arteries of male Sprague-Dawley rats. After the operation, electrodes were
      implanted onto the centre of the fascia of the bilateral tibialis anterior (TA)
      muscles, tunnelled subcutaneously and exteriorized at the level of the scapulae.
      The right TA muscles of rats were stimulated continuously at a stimulus frequency
      of 50 Hz, with a 0.1 V stimulus strength and no interval, for 5 days. The left TA
      muscles served as controls. 3. We found that both VEGF and HGF protein were
      significantly increased by LVES in stimulated muscles compared with control. The
      VEGF level of the LVES group was 89.10 +/- 17.19 ng/g, whereas that of the
      control group was 65.07 +/- 12.88 ng/g, as determined by ELISA (P < 0.05). The
      HGF level of the LVES and control groups was 8.52 +/- 1.96 and 5.80 +/- 2.14
      ng/g, respectively (P < 0.05). In contrast, there was no difference in FGF, IL-6
      and HIF-1alpha between the LVES and control groups. 4. These results suggest that
      LVES in a hindlimb ischaemia model of rats increases not only VEGF, but also HGF,
      production, which may be the main mechanism responsible for the angiogenesis
      produced by LVES.

PMID- 16789932
TI  - Peripheral and centrally mediated effects of insulin on small intestinal transit
      in healthy mice.
AB  - 1. Insulin is the drug of choice in the management of type 1 diabetes mellitus.
      Approximately 76% of diabetic patients suffer from gastrointestinal disorders. An
      important area of investigating the inherent effect of insulin on small
      intestinal transit (SIT) remains unexplored. Hence, the present study was planned
      to investigate the effects of insulin (2 x 10(-6), 2 x 10(-3) and 2 U/kg) on
      small intestinal transit following two different routes of administration in
      healthy animals. 2. Insulin or vehicle was administered subcutaneously or
      intracerebroventricularly in eight groups of healthy, overnight-fasted mice.
      Blood glucose (BG) levels were measured 2 min before insulin administration and
      at the time coinciding with SIT determination. Small intestinal transit was
      determined 50 min after insulin administration using the charcoal meal method. 3.
      Following subcutaneous administration, the lowest dose of insulin (2 x 10(-6)
      U/kg) produced a significant acceleration in SIT without altering BG levels.
      However, the highest dose of insulin (2 U/kg) produced an acceleration of SIT
      that was associated with a significant fall in BG levels. 4. Following
      intracerebroventricular administration, the lowest dose of insulin (2 x 10(-6)
      U/kg) attenuated SIT, without producing any alteration in BG levels, but the
      highest dose (2 U/kg) mimicked the effects seen following subcutaneous
      administration. Peripherally administered insulin produced significant
      acceleration of SIT at lower doses (2 x 10(-6) or 2 x 10(-3) mU/kg) compared with
      centrally administered insulin at similar doses. However, at the highest dose of
      insulin (2 U/kg), both routes (s.c. and i.c.v.) produced acceleration of SIT. 5.
      In the present study, peripherally and centrally administered insulin at 2 x 10(
      6) U/kg produced contrasting effects on SIT, without any hypoglycaemia. However,
      2 U/kg insulin accelerated SIT similarly following both s.c. and i.c.v.
      administration that was associated with hypoglycaemia in healthy animals.

PMID- 16789931
TI  - Effects of sucralfate, cimetidine and rabeprazole on mucosal hydroxyproline
      content in healing of ethanol-hcl-induced gastric lesions.
AB  - 1. No general consensus has been reached on the treatment of acute gastric
      lesions. The aims of the present study were to clarify the effects of sucralfate,
      cimetidine and rabeprazole monotherapies and combination therapies on acute
      gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric
      lesions were experimentally created by the oral administration of 50% ethanol
      0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100
      mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered
      separately or in combination and the stomach was excised at different times to
      measure the level of hydroxyproline in the gastric mucosa and determine lesion
      index. Immunostaining against prolylhydroxylase was performed on some specimens.
      3. In the control group, lesion index decreased linearly from 30 min after
      ethanol-HCl administration and the level of mucosal hydroxyproline peaked between
      2 and 4 h later. Although sucralfate significantly promoted lesion healing, it
      had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in
      mucosal hydroxyproline and prolonged lesion healing, but these findings were
      reversed by combining cimetidine and sucralfate. Rabeprazole had no significant
      effect on lesion healing, but promoted lesion healing in combination with
      sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was
      expressed in spindle cells that lined the glandular cells in a boundary area
      between normal and injured tissues. 4. Under conditions in which the effects of
      intragastric pH are minimal, sucralfate is superior to antisecretory agents in
      promoting the healing of acute gastric lesions.

PMID- 16789933
TI  - Renal preglomerular arterial-venous O2 shunting is a structural anti-oxidant
      defence mechanism of the renal cortex.
AB  - 1. High blood flow to the kidney facilitates a high glomerular filtration rate,
      but total renal O2 delivery greatly exceeds renal metabolic requirements.
      However, tissue Po2 in much of the renal cortex is lower than may be expected,
      being similar to that of other organs in which perfusion is closely matched to
      metabolic demand. 2. The lower than expected renal cortical Po2 is now attributed
      largely to diffusional shunting of as much as 50% of inflowing O2 from blood
      within preglomerular arterial vessels to post-glomerular venous vessels. However,
      the functional significance of this O2 shunting remains unclear. Indeed, this
      mechanism may appear maladaptive, given the kidney's susceptibility to hypoxic
      insults. 3. We hypothesize that renal preglomerular arterial-venous O2 shunting
      acts to protect the kidney from the potentially damaging consequences of tissue
      hyperoxia. The diffusion of O2 from arteries to veins within the kidney acts to
      reduce the O2 content of the blood before it is distributed to the renal
      microcirculation. Because high tissue Po2 may increase the production of reactive
      oxygen species, we suggest that renal arterial-venous O2 shunting may provide a
      physiological benefit to the organism by limiting O2 delivery to renal tissue,
      thereby reducing the risk of cellular oxidation.

PMID- 16789934
TI  - Gene expression of stretch-activated channels and mechanoelectric feedback in the
      heart.
AB  - 1. Mechanoelectric feedback (MEF) in the heart is the process by which mechanical
      forces on the myocardium can change its electrical properties. Mechanoelectric
      feedback has been demonstrated in many animal models, ranging from isolated
      cells, through isolated hearts to whole animals. In humans, MEF has been
      demonstrated directly in both the atria and the ventricles. It seems likely that
      MEF provides either the trigger or the substrate for some types of clinically
      important arrhythmias. 2. Mechanoelectric feedback may arise because of the
      presence of stretch-sensitive (or mechano-sensitive) ion channels in the cell
      membrane of the cardiac myocytes. Two types have been demonstrated: (i) a non
      specific cation channel (stretch-activated channel (SAC); conductance of
      approximately 25 pS); and (ii) a potassium channel with a conductance of
      approximately 100 pS. The gene coding for the SAC has not yet been identified.
      The gene for the potassium channel is likely to be TREK, a member of the tandem
      pore potassium channel gene family. We have recorded stretch-sensitive potassium
      channels in rat isolated myocytes that have the properties of TREK channels
      expressed in heterologous systems. 3. It has been shown that TREK mRNA is
      expressed heterogeneously in the rat ventricular wall, with 17-fold more
      expression in endocardial compared with epicardial cells. This difference is
      reflected in the TREK currents recorded from endocardial and epicardial cells
      using whole-cell patch-clamp techniques, although the difference in current
      density was less pronounced (approximately threefold). Consistent with this, we
      show here that when the ventricle is stretched by inflation of an
      intraventricular balloon in a Langendorff perfused rat isolated heart, action
      potential shortening was more pronounced in the endocardium (30% shortening at 40
      mmHg) compared with that in the epicardium (10% shortening at the same pressure).
      4. Computer models of the mechanics of the (pig) heart show pronounced spatial
      variations in strain in the myocardium with large transmural differences (in the
      left ventricle in particular) and also large differences between the base and
      apex of the ventricle. 5. The importance of MEF and the non-homogeneous gene
      expression and strain distribution for arrhythmias is discussed.

PMID- 16789935
TI  - Mechanosensitive ion channels in skeletal muscle: a link in the membrane
      pathology of muscular dystrophy.
AB  - 1. Mechanosensitive (MS) channels are expressed abundantly in skeletal muscle at
      all stages of development. In recordings from membrane patches, MS channels are
      constitutively active at the resting potential. The channels are selective for
      cations and have a large single-channel conductance (approximately 25 pS in
      physiological saline) and a high Ca2+ permeability (relative permeability of Ca2+
      to K+ (PCa/PK) = 7). 2. Mechanosensitive channel activity recorded from the
      surface of myotubes from dystrophic mdx mice was substantially greater than the
      activity recorded from wild-type myotubes. Increased channel activity in the
      mutant results from the induction in a subpopulation of channels of a novel MS
      gating mode characterized by markedly prolonged channel openings and inactivation
      in response to membrane stretch. 3. Membrane stretch or a strong depolarization
      causes an irreversible switch to the stretch-inactivated gating mode in mdx
      myotubes. A stretch-induced shift in MS channel gating mode may contribute to
      stretch-induced elevations in [Ca2+]i during the early stages of disease
      pathogenesis. 4. Abnormalities of MS channel behaviour are also detected in
      recordings from patches on flexor digitorum brevis fibres acutely isolated from
      mdx mice. Mechanosensitive channel opening probability is higher in mdx fibres at
      all developmental stages. In addition, channel numbers are persistently elevated
      during postnatal development, failing to undergo a normal process of
      downregulation during the first 3 postnatal weeks. 5. Two distinct mechanisms may
      contribute to elevations of [Ca2+]i in dystrophin-deficient skeletal muscle: (i)
      a membrane stress-dependent switch of MS channels into to a prolonged opening
      mode; and (ii) a loss of developmental downregulation leading to persistent MS
      channel expression during postnatal muscle development.

PMID- 16789936
TI  - Muscle damage in mdx (dystrophic) mice: role of calcium and reactive oxygen
      species.
AB  - 1. Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease
      caused by a genetic mutation that leads to the complete absence of the
      cytoskeletal protein dystrophin in muscle fibres. 2. The present review provides
      an overview of some of the physiological pathways that may contribute to muscle
      damage and degeneration in DMD, based primarily on experimental findings in the
      mdx mouse, an animal model of this disease. 3. A rise in intracellular calcium is
      widely thought to be an important initiating event in the dystrophic
      pathogenesis. The pathway(s) leading to increased intracellular calcium in
      dystrophin deficient muscle is uncertain, but recent work from our laboratory
      provides evidence that stretch-activated channels are an important source of the
      calcium influx. Other possible routes of calcium entry are also discussed. 4. The
      consequences of elevated cytosolic calcium may include activation of proteases,
      such as calpain, and increased production of reactive oxygen species (ROS), which
      can cause protein and membrane damage. 5. Another possible cause of damage in
      dystrophic muscle involves inflammatory pathways, such as those mediated by
      neutrophils, macrophages and associated cytokines. There is recent evidence that
      increased ROS may be important in both the activation of and the damage caused by
      this inflammatory pathway in mdx muscle.

PMID- 16789939
TI  - DNA fingerprinting and civil liberties.

PMID- 16789940
TI  - The expanding use of DNA in law enforcement: what role for privacy?

PMID- 16789941
TI  - Is obtaining an arrestee's DNA a valid special needs search under the fourth
      amendment? What should (and will) the Supreme Court do?

PMID- 16789942
TI  - Who needs special needs? On the constitutionality of collecting DNA and other
      biometric data from arrestees.

PMID- 16789943
TI  - California's Proposition 69: a dangerous precedent for criminal DNA databases.

PMID- 16789944
TI  - A communitarian approach: a viewpoint on the study of the legal, ethical and
      policy considerations raised by DNA tests and databases.

PMID- 16789945
TI  - Turning base hits into earned runs: improving the effectiveness of forensic DNA
      data bank programs.

PMID- 16789946
TI  - Inclusiveness, effectiveness and intrusiveness: issues in the developing uses of
      DNA profiling in support of criminal investigations.

PMID- 16789947
TI  - Family ties: the use of DNA offender databases to catch offenders' kin.

PMID- 16789948
TI  - Social and ethical issues in the use of familial searching in forensic
      investigations: insights from family and kinship studies.

PMID- 16789949
TI  - About face: forensic genetic testing for race and visible traits.

PMID- 16789950
TI  - Explaining differential trust of DNA forensic technology: grounded assessment or
      inexplicable paranoia?

PMID- 16789951
TI  - Interrelationships among native peoples, genetic research, and the landscape:
      need for further research into ethical, legal, and social issues.

PMID- 16789952
TI  - Forensic science.

PMID- 16789953
TI  - The impact of DNA exonerations on the criminal justice system.

PMID- 16789954
TI  - Just evidence: the limits of science in the legal process.

PMID- 16789955
TI  - Genes and antisocial behavior: perceived versus real threats to jurisprudence.

PMID- 16789956
TI  - Ethical issues in secondary uses of human biological materials from mass
      disasters.

PMID- 16789957
TI  - Statutory frameworks for regulating information flows: drawing lessons for the
      DNA data banks from other government data systems.

PMID- 16789958
TI  - Should biological evidence or DNA be retained by forensic science laboratories
      after profiling? No, except under narrow legislatively-stipulated conditions.

PMID- 16789959
TI  - Retention of offender DNA samples necessary to ensure and monitor quality of
      forensic DNA efforts: appropriate safeguards exist to protect the DNA samples
      from misuse.

PMID- 16789960
TI  - Let's make the DNA identification database as inclusive as possible.

PMID- 16789961
TI  - Dangerous excursions: the case against expanding forensic DNA databases to
      innocent persons.

PMID- 16789962
TI  - Who owns your body? A patient's perspective on Washington University v. Catalona.

PMID- 16789963
TI  - A consumer perspective on forensic DNA banking.

PMID- 16789964
TI  - Closing the organ gap: a reciprocity-based social contract approach.

PMID- 16789965
TI  - Fiduciary obligation in clinical research.

PMID- 16789966
TI  - Equipoise and the criteria for reasonable action.

PMID- 16789967
TI  - Pediatric assent: subject protection issues among adolescent females enrolled in
      research.

PMID- 16789968
TI  - Informed trust and the financing of biomedical research.

PMID- 16789969
TI  - The ethics and regulation of research with human subjects, Carl Coleman, Jerry
      Menikoff, Jesse Goldner, and Nancy Dubler, eds., (LexisNexis) 2005.

PMID- 16789970
TI  - Civil procedure: First Circuit holds it unreasonable to hale hospitals into
      foreign forums simply for accepting out-of-state patients--Harlow v. Children's
      Hospital.

PMID- 16789971
TI  - Abortion: Supreme Court avoids disturbing abortion precedents by ruling on
      grounds of Remedy-Ayotte v. planned parenthood of Northern New England.

PMID- 16789972
TI  - Appeals Court rejects federal jurisdiction over chiropractors challenge to
      Medicare coverage-Am. Chiropractic Ass'n, Inc. v. Leavitt.

PMID- 16789973
TI  - A journey of hope: lessons learned from studies on rare diseases and orphan
      drugs.
AB  - Rare diseases are frequently life-threatening or chronically debilitating and the
      impact on the quality of life of affected patients and their family members is
      thus significant. However, drug development for these conditions has been limited
      by a lack of understanding of the underlying mechanisms of disease and the
      relative unavailability of subjects for clinical trials, as well as the
      prohibitive cost of investing in a novel pharmaceutical agent with poor market
      potential. Nevertheless, the introduction of Orphan Drug legislations has
      provided important incentives for the development of orphan drugs (i.e. drugs
      that have been abandoned or 'orphaned' by major drug companies). Moreover, recent
      studies on rare diseases, including inherited immunodeficiencies and metabolic
      disorders, have served not only to alleviate the plight of patients with rare
      diseases, but also yielded valuable information on biological processes of
      relevance for other, more common conditions. These lessons, along with the
      crucial importance of cooperation between academic institutions, pharmaceutical
      companies, patient advocacy groups and society in the elucidation of rare
      diseases, are highlighted in the present review.

PMID- 16789974
TI  - Abnormalities of whole body protein turnover, muscle metabolism and levels of
      metabolic hormones in patients with chronic heart failure.
AB  - OBJECTIVE: It is well known that chronic heart failure (CHF) is associated with
      insulin resistance and cachexia, but little is known about the underlying
      substrate metabolism. The present study was undertaken to identify disturbances
      of basal glucose, lipid and protein metabolism. DESIGN: We studied eight
      nondiabetic patients with CHF (ejection fraction 30 +/- 4%) and eight healthy
      controls. Protein metabolism (whole body and regional muscle fluxes) and total
      glucose turnover were isotopically assayed. Substrate oxidation were obtained by
      indirect calorimetry. The metabolic response to exercise was studied by bicycle
      ergometry exercise. RESULTS: Our data confirm that CHF patients have a decreased
      lean body mass. CHF patients are characterised by (i) decreased glucose oxidation
      [glucose oxidation (mg kg(-1) min(-1)): 1.25 +/- 0.09 (patients) vs. 1.55 +/-
      0.09 (controls), P < 0.01] and muscle glucose uptake [a - v diff(glucose)
      (micromol L(-1)): -10 +/- 25 (patients) vs. 70 +/- 22 (controls), P < 0.01], (ii)
      elevated levels of free fatty acids (FFA) [FFA (mmol L(-1)): 0.72 +/- 0.05
      (patients) vs. 0.48 +/- 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and
      signs of elevated fat oxidation and muscle fat utilization [a - v diff(FFA) (mmol
      L(-1)): 0.12 +/- 0.02 (patients) vs. 0.05 +/- 0.01 (controls), P < 0.05] and
      (iii) elevated protein turnover and protein breakdown [phenylalanine flux
      (micromol kg(-1) h(-1)): 36.4 +/- 1.5 (patients) vs. 29.6 +/- 1.3 (controls), P <
      0.01]. Patients had high circulating levels of noradrenaline, glucagon, and
      adiponectin, and low levels of ghrelin. We failed to observe any differences in
      metabolic responses between controls and patients during short-term exercise.
      CONCLUSIONS: In the basal fasting state patients with CHF are characterized by
      several metabolic abnormalities which may contribute to CHF pathophysiology and
      may provide a basis for targeted intervention.

PMID- 16789975
TI  - Impact of follow-up time and re-measurement of the electrocardiogram and
      conventional cardiovascular risk factors on their predictive value for myocardial
      infarction.
AB  - OBJECTIVE: To explore if the predictive power of mid-life electrocardiogram (ECG)
      abnormalities and conventional cardiovascular risk factors for future myocardial
      infarction, change over a 30-year follow-up period and if repeated examination
      improves their predictive power. DESIGN AND SETTING: Longitudinal population
      based study. PARTICIPANTS: A total of 2322 men aged 50 years, with a total follow
      up period of 30 years and 1221 subjects were re-examined at age of 70 years. MAIN
      OUTCOME MEASURE: Risk for fatal and nonfatal myocardial infarction (n = 470)
      analysed at age 50 and 70 years, and separately for 1-10, 11-20 and 21-30 years
      after first examination. Investigations included a 12-lead ECG, blood pressure,
      body mass index, smoking habits, and glucose and lipid variables. RESULTS: Whilst
      high blood pressure and dyslipidaemia variables, such as apolipoprotein
      B/apolipoprotein A1 ratio, measured at age 50 showed an almost unchanged
      predictive power during the three decades of follow up, ECG abnormalities,
      insulin and BMI were only significant predictors during the two first decades of
      follow up. Despite increased prevalences of ECG abnormalities and obesity with
      age, they predicted for future myocardial infarction in midlife only whilst
      fasting insulin and smoking regained their predictive power when re-measured at
      age 70. CONCLUSION: Whilst hypertension and dyslipidaemia were consistent as risk
      factors, length of follow-up period and age at baseline investigations affected
      the predictive power of ECG abnormalities, fasting insulin, BMI and smoking. In
      the elderly, ECG abnormalities did not contribute to the prediction of myocardial
      infarction but smoking and fasting insulin may be important in the
      pathophysiology leading to MI especially in this age group.

PMID- 16789976
TI  - Long-term prognosis in patients with bifascicular block--the predictive value of
      noninvasive and invasive assessment.
AB  - OBJECTIVES: Patients with bifascicular block (BFB) have a high mortality rate.
      The purpose of the present study was to identify high-risk patients in a BFB
      population by performing an extensive cardiac evaluation including noninvasive
      and invasive tests. DESIGN: Population-based study. SUBJECTS: A total of 100
      patients with BFB, of whom 41 had a history of unexplained syncope, were
      prospectively studied. The mean age was 68 +/- 12. All patients were investigated
      with Holter-monitoring, an exercise test, an echocardiography, and an invasive
      electrophysiological study. The severity of congestive heart failure (CHF) was
      assessed by New York Heart Association (NYHA) classification. Patients in NYHA
      class IV were excluded. INTERVENTIONS: Patients with syncope were recommended
      prophylactic pacemaker treatment, which was accepted by 31 patients (76%). Main
      outcome measures. All-cause mortality and sudden cardiac death (SCD). RESULTS:
      During a median follow-up of 84 months, 33 patients died, of whom 14 in SCD. In a
      univariate analysis, high age, a previous myocardial infarction, and CHF were
      associated with a significantly increased risk of all-cause mortality and SCD. In
      a Cox multiple regression analysis, CHF was the only independent predictor of all
      cause mortality and SCD (P < 0.01). CONCLUSION: Patients with BFB have a poor
      long-term prognosis. The predictive value of noninvasive and invasive
      investigations is limited. The only independent predictor of all-cause mortality
      and SCD in this population was the presence of CHF.

PMID- 16789977
TI  - Bystander mouth-to-mouth ventilation and regurgitation during cardiopulmonary
      resuscitation.
AB  - OBJECTIVES: To determine whether there is an association between bystander mouth
      to-mouth ventilation and regurgitation in prehospital cardiac arrest patients.
      DESIGN: Prospectively conducted observational study. SETTING: Data were collected
      from patients treated by the emergency medical service (EMS) systems in three
      middle-sized or large Finnish urban communities, the Tampere District EMS and the
      physician-staffed Helicopter EMSs in the Helsinki and Turku areas in southern
      Finland. SUBJECTS: The study population consisted of 529 consecutive prehospital
      cardiac arrest patients with attempted resuscitation. Exclusion criteria were
      cardiac arrest due to trauma or drug overdose. MAIN OUTCOME MEASURES:
      Regurgitation in prehospital cardiac arrest patients documented by EMS personnel
      on the scene. RESULTS: Regurgitation occurred in a fourth of patients. Bystander
      cardiopulmonary resuscitation (CPR) with mouth-to-mouth ventilation was
      associated with a significantly increased risk of regurgitation compared with no
      CPR (P < 0.013) and CPR without ventilations (P < 0.01). CONCLUSIONS: The mode
      and role of bystander CPR in cardiac arrest needs to be further evaluated.

PMID- 16789978
TI  - Plasma ghrelin concentrations are positively associated with carotid artery
      atherosclerosis in males.
AB  - BACKGROUND: Ghrelin, a peptide hormone from stomach, stimulates food intake and
      decreases fat utilization. Ghrelin binds to growth hormone secretagogue receptor
      (GHSR). GHSR density has been shown to be upregulated in atherosclerotic lesions,
      but the relationship between ghrelin concentration and atherosclerosis has not
      yet been studied. We, therefore, characterized the association between ghrelin
      concentration and carotid artery intima-media thickness (IMT) in a population
      based cohort of 1024 middle-aged (40-60 years) men and women. METHODS: Intima
      media thickness and the number of atherosclerotic plaques were determined
      ultrasonographically. Fasting plasma ghrelin concentrations were analysed using
      RIA-kit (PhoenixPeptide). RESULTS: There was a positive association between mean
      IMT and ghrelin concentration in the analysis of males before and after
      adjustments for the traditional risk factors of atherosclerosis [age, systolic
      blood pressure, LDL cholesterol, body mass index (BMI), and smoking (ancova, P =
      0.004 and P = 0.007, respectively)]. However, no such association was found in
      females (P = 0.985 and P = 0.915). There was no correlation between ghrelin and
      CRP concentrations or ghrelin and smoking. CONCLUSION: Ghrelin concentrations and
      carotid artery atherosclerosis are positively associated in males even after
      adjustment for the commonly recognized risk factors of atherosclerosis.
      Experimental and prospective studies are warranted to elucidate the role of
      ghrelin in atherosclerosis.

PMID- 16789979
TI  - Serum lipid levels in relation to serum thyroid-stimulating hormone and the
      effect of thyroxine treatment on serum lipid levels in subjects with subclinical
      hypothyroidism: the Tromso Study.
AB  - OBJECTIVE: To evaluate the relation between serum thyroid-stimulating hormone
      (TSH) and lipids. DESIGN: Cross-sectional epidemiological study, nested case
      control study, and a placebo-controlled double-blind intervention study. METHODS:
      In the 5th Tromso study serum TSH, total cholesterol (TC), triglycerides (TG),
      high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein
      cholesterol (LDL-C) were measured. Subjects with subclinical hypothyroidism (SHT)
      and a matching control group were re-examined and apolipoprotein A1 (Apo A1) and
      apolipoprotein B (Apo B) were also measured. Subjects with SHT were included in
      an intervention study with thyroxine supplementation for 1 year. RESULTS: A total
      of 5143 subjects from the 5th Tromso study were included. A significant and
      positive correlation between serum TSH levels and serum TC and LDL-C levels were
      found in both genders. However, in the females this did not reach statistical
      significance after adjusting for age and BMI. The serum LDL-C were significantly
      higher and the Apo A1 levels significantly lower in 84 SHT subjects compared with
      145 controls, and in the SHT females the TC levels were also significantly
      elevated. In the intervention study (32 subjects given thyroxine and 32 subjects
      given placebo), we observed a significant reduction in the Apo B levels after
      thyroxine medication. In those that at the end of the study had serum TSH levels
      in the range 0.2-2.0 mIU L(-1), the serum TC and LDL-C levels were also
      significantly reduced. CONCLUSIONS: There is a positive association between serum
      TSH levels and TC and LDL-C levels. These lipid levels are reduced with thyroxine
      treatment in subjects with SHT.

PMID- 16789980
TI  - Noradrenaline and albumin in paracentesis-induced circulatory dysfunction in
      cirrhosis: a randomized pilot study.
AB  - OBJECTIVE: Therapeutic paracentesis in patients with cirrhosis is associated with
      a circulatory dysfunction. Intravenous albumin has been used to prevent the
      circulatory dysfunction; however, the use of albumin is controversial and costly.
      Splanchnic vasodilation is mainly responsible for circulatory dysfunction in
      these patients. There are no reports of use of noradrenaline, a vasoconstrictor,
      on the prevention of paracentesis-induced circulatory dysfunction in patients
      with cirrhosis. Therefore, we studied the preventive effect of noradrenaline on
      paracentesis-induced circulatory dysfunction in patients with cirrhosis after
      therapeutic paracentesis and compared it with that of intravenous albumin in a
      randomized pilot study. METHODS: Forty patients with cirrhosis and tense ascites
      underwent therapeutic paracentesis with albumin or noradrenaline in a randomized
      controlled trial at a tertiary centre. Effective arterial blood volume was
      assessed by measuring plasma renin activity at baseline and at 6 days after
      treatment. RESULTS: Effective arterial blood volume as indicated by plasma renin
      activity before and 6 days after paracentesis did not differ in the two groups
      (20.62 +/- 10.27-22.02 +/- 10.15 ng mL(-1) h(-1); P = 0.11 in the albumin group
      and 19.66 +/- 8.91-20.78 +/- 9.41 ng mL(-1) h(-1); P = 0.37 in the noradrenaline
      group). Plasma aldosterone concentration before and 6 days after paracentesis
      were also similar in both groups (1196.5 +/- 434.2-1217.0 +/- 405.7 pg mL(-1); P
      = 0.7 in the albumin group and 1206.0 +/- 522.5-1273.5 +/- 444.8 pg mL(-1); P =
      0.22 in the noradrenaline group). The cost of noradrenaline treatment was
      significantly lower when compared with that of albumin (P < 0.001). CONCLUSIONS:
      Noradrenaline is as effective as albumin in preventing paracentesis-induced
      circulatory dysfunction in patients with cirrhosis after therapeutic
      paracentesis, but at a fraction of the cost.

PMID- 16789981
TI  - Determination of intrathyroidal iodine by X-ray fluorescence analysis in 60- to
      65-year olds living in an iodine-sufficient area.
AB  - OBJECTIVES: X-ray fluorescence (XRF) is a non-invasive method for determining the
      iodine content of the thyroid gland in vivo. In spite of the obvious clinical
      value of such a method in situations of iodine deficiency or iodine overload, the
      method has not so far been widely used. The objective was to investigate the
      applicability of the XRF method in a larger number of subjects. DESIGN AND
      SUBJECTS: The study comprised 37 individuals, aged 60-65 years, who had spent
      their entire life with iodine supplementation through iodinated table salt.
      Individuals with (previous) thyroid disease were excluded. The individual thyroid
      function had previously been evaluated by measurements of thyroid-related
      hormones, thyroid volume and 131-Iodine (131I) uptake which indicated a
      sufficient iodine intake of the population in the area. Iodine in the right
      thyroid lobe in each subject was examined using XRF. RESULTS: The mean thyroid
      iodine concentration was 0.4 mg mL(-1), corresponding to a mean total iodine
      content of 5.2 mg (range 0.9-20.2). There was a pronounced difference between
      individuals. No correlation was found between iodine concentration and 131I
      uptake or thyroid volume. Neither was iodine content and 131I uptake correlated.
      CONCLUSIONS: In a population living under iodine-sufficient conditions, a large
      variation of iodine stored in the thyroid is compatible with euthyroidism.
      Determination of the iodine pool by XRF investigation is feasible in a clinical
      setting and the method offers a unique possibility to study the intrathyroidal
      iodine pool in subjects with thyroid disease. The low radiation dose enables the
      use of the method in pregnant women and also in young individuals.

PMID- 16789982
TI  - Fracture risk associated with the use of morphine and opiates.
AB  - OBJECTIVES: To study the effect of morphine and opiates on fracture risk. DESIGN:
      Case-control study. SETTING: Nationwide register-based study. SUBJECTS: Cases
      were all subjects with any fracture sustained during the year 2000 (n = 124,655).
      For each case, three controls (n = 373,962) matched on age and gender were
      randomly drawn from the background population. The primary exposure variables
      were use of morphine and opiates. Morphine and other opiates had been used by 10
      015 (8.0%) of the case subjects and 12 108 (3.2%) of the controls. Adjustments
      were made for several confounders including prior fracture, and use of weak
      analgesics [nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) and
      acetaminophene]. The effect of dose was examined by stratifying for cumulated
      dose (defined daily dose). MAIN OUTCOME MEASURE: Fracture. RESULTS: Morphine
      (1.47, 95% CI 1.37-1.58), fentanyl (2.23, 95% CI 1.89-2.64), methadone (1.39, 95%
      CI 1.05-1.83), oxycodone (1.36, 95% CI 1.08-1.69), nicomorphine (1.57, 95% CI
      1.38-1.78), ketobemidone (1.07, 95% CI 1.02-1.13), tramadol (1.54, 95% CI 1.49
      1.58) and codeine (1.16, 95% CI 1.12-1.20) were all associated with an increase
      in overall fracture risk. No increase was present for buprenorphine (0.86, 95% CI
      0.79-0.95), pethidine (0.98, 95% CI 0.89-1.08), dextropropoxiphene (1.02, 95% CI
      0.90-1.16), and combinations of ASA and codeine (0.94, 95% CI 0.88-1.01).
      CONCLUSIONS: An increased fracture risk is seen in users of morphine and opiates.
      The reason for this may be related to the risk of falls due to central nervous
      system effects such as dizziness.

PMID- 16789983
TI  - What are the professional and logistic demands to appropriately follow patients
      with an implantable cardioverter-defibrillator?
AB  - OBJECTIVES: To determine events during follow-up of patients with implantable
      cardioverter-defibrillators (ICD) and the specific experience cardiologists need
      for trouble-shooting. DESIGN: Prospective evaluation of all patient visits in an
      outpatient clinic. SETTING: University hospital, single centre performing ICD
      controls in a region of 1.5 Mio inhabitants. SUBJECTS: A total of 351 patients
      with 1118 consecutive visits during 14 months. INTERVENTIONS: Classification of
      events according to predefined training levels. MAIN OUTCOME MEASUREMENTS: Skill
      levels A: simple visit, e.g. for switching the device 'off'. B: normal visit, no
      further measures taken (no device reprogramming), even though the patient might
      have experienced ICD interventions. C: complex visit, electrophysiologist
      actively involved. Correlation of these levels with timing (routine, emergency
      on/off office hours) and reason of visits. RESULTS: Seventy-six per cent of
      visits were scheduled routine visits, 5% performed within 24 h because of shocks,
      19% performed for other reasons (shock tests; switching the device 'off/on';
      reported dizziness, syncope, palpitations without ICD interventions). Required
      skill levels were A in 44 (4%), B in 796 (71%) and C in 278 (25%) visits.
      Emergency visits were more often classified as level C (60%) than regular visits
      (20%), Skill level C was more often encountered during emergency (30%) than
      during regular visits (6%) (both P = 0.001). CONCLUSIONS: Our study suggests that
      for standard follow-up in patients without obvious problems, a cardiologist might
      be sufficient, whereas presentations due to/with clinical problems most likely
      will need the expertise of an electrophysiologist.

PMID- 16789984
TI  - CRB-65 predicts death from community-acquired pneumonia.
AB  - OBJECTIVE: The study was performed to validate the CURB, CRB and CRB-65 scores
      for the prediction of death from community-acquired pneumonia (CAP) in both the
      hospital and out-patient setting. DESIGN: Data were derived from a large multi
      centre prospective study initiated by the German competence network for community
      acquired pneumonia (CAPNETZ) which started in March 2003 and were censored for
      this analysis in October 2004. SETTING: Out- and in-hospital patients in 670
      private practices and 10 clinical centres. SUBJECTS: Analysis was done for n =
      1343 patients (n = 208 out-patients and n = 1135 hospitalized) with all data sets
      completed for the calculation of CURB and repeated for n = 1967 patients (n = 482
      out-patients and n = 1485 hospitalized) with complete data sets for CRB and CRB
      65. INTERVENTION: None. 30-day mortality from CAP was determined by personal
      contacts or a structured interview. RESULTS: Overall 30-day mortality was 4.3%
      (0.6% in out-patients and 5.5% in hospitalized patients, P < 0.0001). Overall,
      the CURB, CRB and CRB-65 scores provided comparable predictions for death from
      CAP as determined by receiver-operator-characteristics (ROC) curves. However, in
      hospitalized patients, CRB misclassified 26% of deaths as low risk patients.
      Availability of the CRB-65 score (90%) was far superior to that of CURB (65%),
      due to missing blood urea nitrogen values (P < 0.001). CONCLUSIONS: Both the CURB
      and CRB-65 scores can be used in the hospital and out-patients setting to assess
      pneumonia severity and the risk of death. Given that the CRB-65 is easier to
      handle, we favour the use of CRB-65 where blood urea nitrogen is unavailable.

PMID- 16789985
TI  - Do pharmacy staff recommend evidenced-based smoking cessation products? A pseudo
      patron study.
AB  - OBJECTIVE: To determine whether pharmacy staff recommend evidence-based smoking
      cessation aids. METHODS: Pseudo patron visit to 50 randomly selected Sydney
      pharmacies where the pseudo patron enquired about the 'best' way to quit smoking
      and about the efficacy of a non-evidence-based cessation product, NicoBloc.
      RESULTS: Nicotine replacement therapy was universally stocked and the first
      product recommended by 90% of pharmacies. After prompting, 60% of pharmacies,
      either also recommended NicoBloc or deferred to 'customer choice'. About 34%
      disparaged the product. CONCLUSIONS: Evidence-based smoking cessation advice in
      Sydney pharmacies is fragile and may be compromised by commercial concerns.
      Smokers should be provided with independent point-of-sale summaries of evidence
      of cessation product effectiveness and warned about unsubstantiated claims.

PMID- 16789986
TI  - Population pharmacokinetic modelling of carbamazepine in epileptic elderly
      patients: implications for dosage.
AB  - BACKGROUND: Proper use of antiepileptic drugs in the elderly involves knowledge
      of their pharmacokinetics to ensure a patient-specific balance between efficacy
      and toxicity. However, populations of epileptic patients on chronic carbamazepine
      (CBZ) therapy which have been studied have included data of relatively few
      elderly patients. AIMS: The aim of the present study was to evaluate the
      population pharmacokinetics of CBZ in elderly patients on chronic monotherapy.
      METHODS: We have used the non-parametric expectation maximization (NPEM) program
      in the USC*PACK collection of PC programs to estimate individual and population
      post-induction pharmacokinetics of CBZ in epileptic elderly patients who received
      chronic CBZ monotherapy. Age-related changes of CBZ population pharmacokinetics
      were evaluated from routine therapeutic drug monitoring (TDM) data of 37 elderly
      and 35 younger patients with epilepsy. As a 'historical control' we used
      previously published population modelling results from 99 young epileptic
      patients on chronic CBZ monotherapy. In that control group, TDM was performed in
      the same pharmacokinetic (PK) laboratory, using the same sampling strategy as in
      the present study, and the same PK population modelling software was used for
      data analysis. RESULTS AND CONCLUSIONS: A poor correlation was found between
      daily CBZ dose and serum concentrations in the elderly patients (r=0.2, P=0.25).
      Probably statistically significant difference in the median values of the CBZ
      metabolic rate constant (P<0.001) between elderly and relatively young epileptic
      patients was found. Our results showed that age-related influences in CBZ
      pharmacokinetics in elderly patients should be considered in the optimal planning
      of CBZ dosage regimens. Most elderly patients with epilepsy will usually need CBZ
      dosages lower than those based on the median population PK parameter values
      obtained from younger patients. The present population model is also uniquely
      well suited for the new 'multiple model' design of dosage regimens to hit target
      therapeutic goals with maximum precision.

PMID- 16789987
TI  - Applying preventable drug-related morbidity indicators to the electronic patient
      record in UK primary care: methodological development.
AB  - BACKGROUND AND OBJECTIVE: Measuring and assessing the quality of health care
      services is an issue of high international importance. Providing data can be
      reliably extracted, making use of the electronic patient record (EPR) could help
      practitioners fulfil clinical governance obligations and ultimately improve the
      quality of patient care. The objective of this paper is to describe (i) the
      process used to apply a series of clinical indicators for preventable drug
      related morbidity (PDRM) in the EPR, (ii) problems encountered and (iii) our
      attempts to resolve them. METHOD: The PDRM indicators were applied
      retrospectively in the EPR of all patients aged 18 years and over in nine general
      practices using the Morbidity Information and Query Export Syntax (MIQUEST)
      computer software programme. RESULTS: Issues identified as requiring attention
      when attempting to extract data from the EPR include considering the ranges to be
      used for age and biochemical test results, accuracy of diagnosis and drug coding,
      the level of complexity of the information needed, and how best to manipulate the
      resulting data. Practical difficulties encountered were ensuring the query coding
      schemes were sufficiently robust and comprehensive to secure reliable data
      extraction, the number of MIQUEST queries required to express each indicator, the
      time-consuming nature of the stages involved in the data manipulation process.
      DISCUSSION: Despite some practical difficulties, we have successfully used
      MIQUEST to identify potential preventable drug-related morbidities from the EPR.
      The quality of information that can be extracted from the EPR is obviously
      limited by the accuracy and completeness of the data on the system and the
      ability of the enquirer to reliably extract and manipulate that data. CONCLUSION:
      Although some of the problems encountered were specific to the MIQUEST software,
      many, including considering appropriate ranges for age and biochemical test
      results and paying careful attention to the reliability of drug and diagnosis
      coding, are relevant whenever data are extracted from the EPR for any purpose.

PMID- 16789988
TI  - Cefepime vs. Ampicillin/Sulbactam and Aztreonam as antibiotic prophylaxis in
      neurosurgical patients with external ventricular drain: result of a prospective
      randomized controlled clinical trial.
AB  - INTRODUCTION: We aimed to find out whether single board spectrum antibiotic
      prophylaxis was as good as dual specific antibiotic prophylaxis in neurosurgical
      patients with external ventricular drain (EVD) in situ. METHOD: In a 2-year
      period, 255 eligible patients were recruited. Patients were randomized into two
      groups of antibiotic prophylaxis as long as the ventricular catheter in situ.
      Group A employed Cefepime 2G 12 hourly and Group B employed dual antibiotics as
      Ampicillin/Sulbactam 3 g 8 hourly and Aztrenam 2 g 8 hourly. RESULTS: There was
      no statistically significant difference in cerebrospinal fluid (CSF) infection
      rate with 14 patients (11.5%) in group A (Cefepime prophylaxis) and eight
      patients (6.0%) in group B (dual prophylaxis with Ampicillin/Sulbactam and
      Aztrenam) had CSF infection (P=0.18). There was also no statistical significant
      difference between wound infection rate happened in eight patients (6.6%) in
      Group A and three patients (2.3%) in Group B (P=0.17). There was no statistical
      significant difference in extracranial infection rate between both groups
      (P=0.70). CONCLUSION: Single board spectrum antibiotic prophylaxis with Cefepime
      was an effective alternative regimen for neurosurgical patients with an EVD in
      situ.

PMID- 16789989
TI  - Serum amiodarone and desethylamiodarone concentrations following nasogastric
      versus oral administration.
AB  - OBJECTIVE: Hospitalized patients unable to ingest anything by mouth require
      nutritional support by enteral feeding and administration of drugs through a
      nasogastric tube inserted into the digestive tract. Nasogastric administration of
      amiodarone may not always be equivalent to oral administration of amiodarone.
      METHODS: We collected 162 observations of serum amiodarone and desethylamiodarone
      metabolite concentrations from 93 patients within 60 days of starting treatment
      with amiodarone. Eight patients were given the drug nasogastrically and 85
      patients, orally. The two groups, were compared in terms of their serum
      concentration/(dose/weight) (C/D) value. A ratio of serum amiodarone
      concentration to serum desethylamiodarone concentration (AMD/DEA) was calculated
      for each sample. In addition, the percentage drug recovery after nasogastric
      administration of amiodarone was analysed. RESULTS: Significant differences were
      observed in C/D values of amiodarone and desethylamiodarone and in AMD/DEA values
      of patients given amiodarone orally when compared with those given the drug
      nasogastrically. The C/D values of patients who received their medication
      nasogastrically were approximately 30% of the C/D values of patients who received
      their medication orally. Approximately 70% of the drug was recovered after it had
      passed through the nasogastric tube. CONCLUSIONS: To achieve similar
      concentrations, an approximately 3-fold increase in dosage of amiodarone was
      required when patients were given the drug nasogastrically rather than orally.
      This suggests that the absorption of amiodarone following nasogastric
      administration is poor when compared with oral administration. Therapeutic drug
      monitoring is necessary to optimize dose particularly during the early stages of
      amiodarone therapy.

PMID- 16789990
TI  - Appropriateness of antiviral prescribing for influenza in primary care: a
      retrospective analysis.
AB  - BACKGROUND AND OBJECTIVE: Antiviral medications cost-effectively reduce influenza
      related morbidity and potentially mortality. We sought to assess the
      appropriateness of antiviral prescribing for influenza. METHOD: We performed a
      retrospective analysis of visits by adults to primary care clinics during
      influenza seasons from 1 October 2000 to 31 May 2004 with a claims diagnosis of
      influenza (n=535) or with an electronic antiviral prescription (n=25). We defined
      appropriate antiviral prescribing as the patient having (a) symptoms for 2 or
      fewer days, (b) fever and (c) any two of headache, sore throat, cough, or
      myalgias. RESULTS AND DISCUSSION: Physicians diagnosed patients with influenza in
      102 of 535 (19%) visits with a claims diagnosis of influenza. Physicians
      prescribed antivirals at 15 of 102 (15%) of these visits. The addition of 25
      additional electronic antiviral prescriptions gave a sample of 127 visits and 40
      (31%) antiviral prescriptions. Twenty-eight (70%) antiviral prescriptions were
      appropriate. Among patients who did not receive antivirals, 21 of 87 (24%) met
      criteria for appropriate antiviral prescribing. Antiviral prescribing was
      associated with a shorter median symptom duration (2 days vs. 3 days; P<0.01) and
      higher median temperature (37.8 degrees C vs. 36.9 degrees C; P<0.01). Physicians
      prescribed antivirals more frequently to patients who had myalgias (37% vs. 18%;
      P=0.04) and an influenza test (67% vs. 28%; P<0.01). Physicians prescribed
      antivirals more frequently to Blacks (44%) and patients with other race/ethnicity
      (67%) than to Whites (20%) or Hispanics (20%; P<0.0001). CONCLUSIONS: To improve
      antiviral prescribing for influenza in primary care, interventions need to target
      the accurate identification of influenza visits, undertreatment, as well as
      inappropriate treatment.

PMID- 16789991
TI  - Improving compliance in depression: a systematic review of narrative reviews.
AB  - BACKGROUND AND OBJECTIVE: Narrative reviews represent a popular source of
      information for clinicians, especially where the evidence on a given subject is
      sparse and analogies from other fields of medicine may help in filling the
      information gap. Unfortunately, narrative reviews often follow less stringent
      criteria for information selection and appraisal than systematic reviews,
      potentially leading to incomplete or biased recommendations. The objective of the
      present study was to examine the quality of the recommendations provided by
      narrative reviews on how to improve patient adherence to pharmacological
      treatment of unipolar depressive disorders. METHOD: We sought to locate all
      narrative review papers addressing adherence to treatment in unipolar depressive
      disorders. In order to do so, we searched Medline and PsychInfo from 1980 to
      December 2003, using the following keywords: review, depressive disorders,
      treatment, dropout, patient compliance and adherence. We inspected the title and
      the abstract, whenever available to identify the relevant reviews and obtained a
      full copy of the publications in this subset, and read the articles to identify
      further relevant reviews. These were in turn copied and reviewed, until no
      further references were found. RESULTS AND DISCUSSION: We identified 23 reviews,
      providing a total of 87 recommendations. The most common recommendation was for
      patient education (19 times), patient-physician empathy/alliance (14 times), and
      education of family (nine times). Reviewers' recommendations were based on the
      literature on depression 54 times, and on other medical conditions 17 times. A
      critical appraisal of the evidence base of the recommendations showed that
      randomized controlled trials or meta-analyses were quoted to support the
      recommendations only 23% of the times, while important interventions of proven
      efficacy in the field of depression or in other chronic conditions (e.g.
      medication clinics, training of nurses, psychological treatment, and telephone
      follow-up) were not mentioned. CONCLUSIONS: Narrative reviews on adherence to
      pharmacological treatment of depressive disorders suffer not only from the
      limited availability of good quality evidence, but also from an incomplete
      critical appraisal of available evidence on interventions both for depression and
      for other chronic disorders.

PMID- 16789992
TI  - Magnetic resonance spectroscopy for measuring the biodistribution and in situ in
      vivo pharmacokinetics of fluorinated compounds: validation using an investigation
      of liver and heart disposition of tecastemizole.
AB  - BACKGROUND AND OBJECTIVE: The study of biodistribution and in situ
      pharmacokinetics is a challenging, but sometimes very important, aspect of
      premarketing characterization of drugs. We aimed to develop a non-invasive
      fluorine magnetic resonance (MR) spectroscopic method for the absolute
      quantitation of a mono-fluorinated compound and of its metabolites in the heart
      and liver of healthy subjects for this purpose. METHOD: We used fluorine MR
      spectroscopy (MRS) at 4 T (Tesla) and external standardization in an open label
      multiple-dose study. Twenty-three healthy adult subjects were enrolled in the
      study. The surface coil localized fluorine MR spectrum was monitored in the heart
      and liver at baseline and after oral administration of multiple doses of
      tecastemizole. Steady-state measurements were made at set time points that
      depended upon dose, and washout measurements were made only on subjects in which
      in vivo fluorine signal was observed. RESULTS AND DISCUSSION: At 4 T, under the
      given experimental conditions, the method had a lower limit of quantitation
      (LLOQ) of about 2.6 microm and a limit of detection (LOD) of about 0.3 microm for
      solution state samples (linewidth approximately 15 Hz). The measurement
      reproducibility was 6.4% using a 50 microm phantom. The effect of MR operator and
      spectral analyst on the calculated calibration curve slope was small, with inter
      rater correlation coefficients of 0.999 and 0.998 respectively. MR signal from
      fluorine-containing tecastemizole-related moieties was observed in situ only at
      day 8 in the liver of three of five subjects dosed at 270 mg/day. The average in
      situ concentration was estimated to be 58+/-22 microm, with an average test
      retest reproducibility of 216%. Extrapolating the in vitro results to human
      measurements, with an approximate linewidth of 250 Hz, predicts in situ LOD and
      LLOQ values of approximately 6 and 44 microm respectively. However, the human
      study had a fluorine MRS LOD of approximately 20 microm. The decrease in
      sensitivity and the increase in variability of the in vivo, in situ measurements
      compared with the validation study most likely arose from coil placement and
      incomplete rephasing of the MR signal by the respiratory phase compensation
      method. CONCLUSION: The measured concentrations were the lowest ever recorded for
      a multi-dose exogenous mono-fluorinated compound in the human liver using a
      validated fluorine MR quantitation method. The proposed non-invasive MR method
      for studying the biodistribution and in situ pharmacokinetics of mono-fluorinated
      compounds in the liver and heart should have broader application to the
      development of non-invasive biomarkers.

PMID- 16789993
TI  - Effect of CYP2C19 genetic polymorphism on pharmacokinetics of phenytoin and
      phenobarbital in Japanese epileptic patients using Non-linear Mixed Effects Model
      approach.
AB  - OBJECTIVE: To clarify the effect of genetic polymorphism of CYP2C19 on
      pharmacokinetics of phenytoin and phenobarbital using a Non-linear Mixed Effects
      Modelling analysis in Japanese epileptic patients. METHOD: A total of 326 serum
      phenytoin concentrations were collected from 132 patients, and a total of 144
      serum phenobarbital concentrations were collected from 74 patients during their
      clinical routine care. RESULT: The maximal elimination rate of phenytoin
      decreased by 10.2% in patients with CYP2C19*1/*2 compared with patients with
      normal CYP2C19. The Michaelis-Menten constants in the patients with CYP2C19*1/*3
      and the poor metabolizers of (CYP2C19*2/*2 or *2/*3 or *3/*3) were 27% and 54%
      higher than those for the patients with normal CYP2C19, respectively. The total
      body clearance of phenobarbital decreased by 19.3% in patients with CYP2C19*1/*3
      or the poor metabolizers of CYP2C19 compared with patients with normal CYP2C19 or
      with CYP2C19*1/*2. CONCLUSION: These findings indicated that the genetic
      polymorphisms of CYP2C19 contribute to the pharmacokinetic variability of
      phenytoin and phenobarbital, the poor metabolizers of CYP2C19, which are
      relatively common in Asian groups.

PMID- 16789994
TI  - Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic
      population isolate of Sardinia.
AB  - BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an enzyme involved in the
      normal metabolic inactivation of thiopurine drugs. Patients with intermediate or
      no TPMT activity are at risk of toxicity after receiving standard doses of
      thiopurine drugs and it was shown that inter-individual differences in response
      to these drugs is largely determined by genetic variation at the TPMT locus.
      OBJECTIVE: This study was designed to investigate in the Sardinian population the
      frequency distribution of four of the most common variants accounting for TPMT
      deficiency and to conduct comparative analyses with other populations in order to
      obtain insights into the main factors that have shaped diversity at the TPMT
      locus in Sardinia. METHODS: DNA was extracted in 259 Sardinians and the
      frequencies of allelic variants of TPMT were determined using polymerase chain
      reaction-restriction fragment length polymorphism technique. RESULTS: Among the
      259 Sardinians genotyped, 6.95% were found to be heterozygous for one of four
      TPMT variants screened; for each variant the frequency estimate was 1.74%, 0.58%,
      0.39% and 0.77% for TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C respectively.
      CONCLUSIONS: Although Sardinia does not show reduced diversity at the TPMT locus,
      the spectrum of TPMT allele frequencies affords evidence of remarkable influence
      of genetic drift and founder effects throughout its population history. In the
      broad context of the European TPMT diversity, the Sardinians come out as
      outliers, an observation consistent with previous genetic inferences that
      Sardinia has features of a genetic isolate.

PMID- 16789995
TI  - Is brimonidine ophthalmic a safe therapy for infants?
AB  - Brimonidine is a topical alpha-2 agonist commonly used in the treatment of
      glaucoma. Brimonidine toxicity resembles that of clonidine overdose and is
      probably due to both imidazoline and alpha-2 adrenergic receptor effects. We
      report a case of a 6-week-old infant with congenital glaucoma who developed
      bradycardia and hypotension following the administration of brimonidine 0.15%
      ophthalmic solution. There are occasional reports of brimonidine toxicity in the
      paediatric population but its overall safety profile in children<2 years of age
      remains uncertain. Brimonidine is not dosed by weight and therefore paediatric
      patients may be at increased risk for systemic toxicity. It is recommended that
      the use of this medication be carefully considered in children<2 years of age.
      Physicians should be aware of its side effect profile because of its general use
      in the paediatric population.

PMID- 16789998
TI  - Smoking cessation.

PMID- 16789996
TI  - Acute isolated tuberculous appendicitis.
AB  - Non-pulmonary tuberculosis is found with different frequencies in different
      countries of the world. It is said to constitute about 4% of all tuberculosis
      cases in Poland, about 25% in England and Wales and about 17% in the USA. It
      seems that these differences are the result of differences in rates of diagnosis
      and registration of new tuberculosis cases. This in turn is influenced by public
      health funding in the individual countries. In this work, we present a case of
      acute, isolated, tuberculous inflammation of the appendix. We call attention to
      the fact that pre-operative diagnosis is practically impossible. Clinical
      symptoms do not point to inflammatory changes. Only surgical evaluation, and
      especially the result of histopathological examination make it to possible to
      establish the final diagnosis to initiation of anti-tuberculous treatment.

PMID- 16790000
TI  - Annotation: Pathways to care for children with mental health problems.
AB  - BACKGROUND: Although many children with mental health problems are in contact
      with primary health care services, few receive appropriate help. METHODS: Using a
      pathways to care model, this paper systematically reviews the literature relating
      to access to services. It separates out the various stages of help-seeking:
      parental perception of problems, use of primary care services, recognition within
      primary care, and referral to or use of specialist health services. RESULTS:
      Following parental awareness of child symptoms, parental perception of problems
      is the key initial step in the help-seeking process. Although children with
      mental health problems or disorders are regular attenders within primary care and
      most parents acknowledge that it is appropriate to discuss concerns about
      psychosocial issues in this setting, few children are presented with mental
      health symptoms even if their parents have such concerns. Subsequently, less than
      half of children with disorders are recognised in primary care. Amongst
      recognised children, about half are referred to specialist services. Overall, up
      to one-third of children with disorders receive services for mental health
      problems. Factors such as the type and severity of disorder, parental
      perceptions, child age and gender, and family and social background factors
      determine which affected children access services. CONCLUSIONS: As there are
      inequities in patterns of service use, a greater emphasis on developing resources
      at population and primary care levels is required. Barriers involving parental
      perceptions and expression of concerns within consultations should be minimised
      at these levels. This requires both public education approaches and improved
      training and specialist support for primary care services to enhance their
      ability to provide for these children.

PMID- 16790001
TI  - Maternal attachment state of mind moderates the impact of postnatal depression on
      infant attachment.
AB  - BACKGROUND: Empirical studies have revealed a significant, but modest association
      between maternal depression and insecure mother-child attachment. Across studies,
      however, a substantial number of mothers with depression are able to provide a
      sensitive caretaking environment for their children. This paper aimed to explore
      whether a mother's own state of mind regarding attachment moderated the
      association between postpartum depression and insecure mother-child attachment.
      METHODS: Mothers (n = 111), mainly middle-class mothers, and their infants
      participated in a longitudinal study of postnatal depression, maternal attachment
      state of mind and child attachment. Depression was assessed using a diagnostic
      interview (at 4 and 12 months) and symptom checklists (at 4, 12 and 15 months).
      The Adult Attachment Interview was conducted at 12 months and the Strange
      Situation procedure at 15 months. RESULTS: Mothers diagnosed as depressed were
      more likely to have an insecure state of mind regarding attachment. Infants of
      chronically depressed mothers were more likely to be insecurely attached;
      however, the relationship between maternal depression and child attachment was
      moderated by maternal attachment state of mind. CONCLUSIONS: Results are
      discussed with reference to resiliency factors for women with postnatal
      depression and implications for intervention.

PMID- 16790002
TI  - Making up is hard to do, especially for mothers with high levels of depressive
      symptoms and their infant sons.
AB  - BACKGROUND: The goal of this study was to evaluate the interactions of mothers
      with normative or high levels of depressive symptomatology on the Center for
      Epidemiologic Studies-Depression Scale (CES-D) and their 3-month-old infants.
      Although successful mutual regulation of affect is critical to children's socio
      emotional development, little is known about the factors that influence dyadic
      processes such as synchrony, matching, mismatching, and bi-directionality during
      early infancy. Therefore, this study evaluated the effects of maternal depressive
      symptom status, infant gender, and interactional context on mother-infant
      affective expressiveness and the dyadic features of their interactions. METHODS:
      Participants were 133 mothers and their healthy full-term infants. Mothers were
      classified into three groups on the basis of their total score on the CES-D at 2
      months of infant age: a high symptom group (CES-D score > or = 16), a mid symptom
      control group (CES-D score = 2-12), and a low symptom group (CES-D score = 0-1).
      Mothers and infants were then videotaped in the Face-to-Face Still-Face paradigm
      at 3 months of infant age. The mothers' and infants' affect during the
      interactions prior to (first play) and following the still-face (reunion play)
      were coded microanalytically using Izard's AFFEX system. RESULTS: Results
      indicated that male as compared to female infants were more vulnerable to high
      levels of maternal depressive symptoms and that high symptom mothers and their
      sons had more difficult interactions in the challenging reunion episode.
      CONCLUSIONS: The findings suggest that a cycle of mutual regulatory problems may
      become established between high symptom mothers and their sons, particularly in
      challenging social contexts. The long-term consequences of this early social
      interactive vulnerability in terms of later development need to be further
      investigated.

PMID- 16790003
TI  - Temperament, parenting, and depressive symptoms in a population sample of
      preadolescents.
AB  - BACKGROUND: Depressive symptoms can be triggered by negative social experiences
      and individuals' processing of these experiences. This study focuses on the
      interaction between temperament, perceived parenting, and gender in relation to
      depressive problems in a Dutch population sample of preadolescents. METHODS: The
      sample consisted of 2230 ten-to-twelve-year-olds from the North of The
      Netherlands. Perceived parenting (overprotection, rejection, emotional warmth)
      was assessed by the EMBU (a Swedish acronym for My Memories of Upbringing) for
      Children, temperament (fearfulness and frustration) by the parent version of the
      Early Adolescent Temperament Questionnaire-Revised, and depressive problems by
      the Child Behavior Checklist (parent report) and the Youth Self-Report (child
      report). RESULTS: All parenting and temperament factors were significantly
      associated with depressive problems. Frustration increased the depressogenic
      effect of parental overprotection and lack of emotional warmth. Fearfulness
      increased the effect of rejection in girls, but not in boys. Furthermore, the
      association between frustration and depression was stronger in boys. CONCLUSIONS:
      These findings support the hypothesis that the effect of specific parenting
      behaviors depends on the temperament and gender of the child.

PMID- 16790004
TI  - I think, therefore I am: a twin study of attributional style in adolescents.
AB  - BACKGROUND: Parenting factors may be important to the development of
      attributional style in adolescence, which in turn relates to depression symptoms.
      These relationships have mainly been considered in terms of social risk
      mechanisms, and little is known about the role of genetic influences. METHOD:
      Self-reported measures of attributional style, depression symptoms and parental
      disciplinary styles were administered to over 1300 adolescent twin and sibling
      pairs. Model-fitting techniques were used to examine the role of genetic and
      environmental influences. RESULTS: Moderate genetic influences on attributional
      style were demonstrated, and furthermore, its association with depression
      reflected considerable genetic effects. Familial factors were implicated in the
      association between attributional style and punitive parenting, although genetic
      from shared environmental causes could not be distinguished. CONCLUSIONS: Our
      results demonstrate that attributional style is influenced by genetic, as well as
      social factors. Implications for aetiological pathways integrating cognitive,
      genetic and social factors on adolescent depression are discussed.

PMID- 16790005
TI  - A comparison of pure and comorbid CD/ODD and depression.
AB  - BACKGROUND: We studied the symptomatology of conduct/oppositional defiant
      disorder and major depression/dysthymic disorder in 'pure' and comorbid
      presentations. METHOD: The sample comprised 382 children of 8 to 17 years of age
      attending for psychiatric outpatient consultation. Ninety-two had depressive
      disorders without conduct disorders, 165 conduct disorder or oppositional defiant
      disorder without depressive disorders and 125 had both. RESULTS: In general,
      there were few differences in the distributions of the symptoms of shared
      disorders between the pure and the comorbid groups. Comorbidity accentuated
      depressive and emotional symptoms and functional impairment. After controlling
      for the presence of other disorders and severity of symptoms, comorbid children
      were more globally impaired than the pure conduct group and more impaired than
      the pure depressive group in school, the home, and in relationships with other
      people. CONCLUSIONS: The clinical presentations of 'pure' and comorbid depressive
      and conduct disorders are similar. Differences found in phenomenology and in
      functional impairment between the groups have implications for treatment planning
      and for nosology.

PMID- 16790006
TI  - Stability, correlates, and outcome of adolescent suicidal risk.
AB  - BACKGROUND: The goal of this study was to investigate the stability and
      correlates of adolescent suicidal risk across adolescence. METHODS: Suicidal risk
      was studied longitudinally in N = 593 subjects in 1994, 1997, and 2001 at mean
      ages of 13, 16, and 20 years. Three partly overlapping suicidal risk groups were
      compared to three control groups matched by age and gender regarding behavioural
      and emotional problems, number and impact of life events, coping capacities, self
      related cognitions, and the size and efficiency of the social network.
      Psychiatric diagnoses were obtained in young adulthood. RESULTS: The group
      stability of suicidal risk was 43% from time 1 to time 2 and 18% from time 1 to
      time 3. Intra-individual stability of suicidal risks across adolescence was
      significantly higher than expected. At all three times of assessment, there was a
      clear excess of abnormal psychosocial findings in the suicidal risk groups as
      compared to the matched controls. Substance abuse disorders, depressive
      disorders, phobias and any psychiatric disorders in young adulthood were
      predicted by suicidal risk in preadolescence irrespective of behavioural and
      emotional disorders. CONCLUSIONS: Suicidal risk individuals are remarkably stable
      across adolescence and show a very consistent pattern of associated behavioural
      and emotional problems and psychosocial variables across time from preadolescence
      to young adulthood. They also display an increased risk for some mental disorders
      in young adulthood.

PMID- 16790007
TI  - Suicide attempts and severe psychiatric morbidity among former child welfare
      clients--a national cohort study.
AB  - BACKGROUND: Few large sample studies have examined psychiatric morbidity among
      former child welfare/protection clients. In this study, risks for suicide
      attempts and severe psychiatric morbidity in younger years were assessed for
      former child welfare clients in ten national birth cohorts, comparing them with
      general population peers and inter-country adoptees. METHODS: We used national
      register data for almost one million people: 22,305 former child welfare clients
      who had experienced interventions before their teens, 955,326 general population
      cohort peers and 12,240 inter-country adoptees. Multivariate Cox regression
      models were used to estimate risks of hospitalisation for suicide attempts and
      psychiatric disorders from age 13 to age 18-27. RESULTS: Former child welfare
      clients were in year of birth and sex standardised risk ratios (RRs) four to five
      times more likely than peers in the general population to have been hospitalised
      for suicide attempts. They were five to eight times more likely to have been
      hospitalised for serious psychiatric disorders in their teens, four to six times
      in young adulthood. High excess risks were also found for psychoses and
      depression. Individuals who had been in long-term foster care tended to have the
      most dismal outcome. Adjusting for birth parents' hospitalisations with a
      psychiatric diagnosis or for substance abuse, and for birth-home-related socio
      economic factors, reduced excess risks to around twofold. CONCLUSIONS:
      Irrespective of issues of causality, findings suggest that former child
      welfare/protection clients should be considered a high-risk group for suicide
      attempts and severe psychiatric morbidity. Results have substantial practice
      implications for mental health and social agencies serving this group in
      adolescence and/or young adulthood.

PMID- 16790008
TI  - Heritability for adolescent antisocial behavior differs with socioeconomic
      status: gene-environment interaction.
AB  - BACKGROUND: Socioeconomic status is often assumed to be of importance for the
      development of antisocial behavior, yet it explains only a fraction of the
      variance. One explanation for this paradox could be that socioeconomic status
      moderates the influence of genetic and environmental effects on antisocial
      behavior. METHOD: TCHAD is a Swedish longitudinal population-based twin study
      that contains 1,480 twin pairs born 1985-1986. The present study included 1,133
      twin pairs, aged 16-17 years. Antisocial behavior was measured through self
      report. Family socioeconomic status was assessed by parental-reported education
      and occupational status. Neighborhood socioeconomic conditions were assessed
      using five aggregated level variables: ethnic diversity, basic educational level,
      unemployment level, buying power, and crime-rate. We used structural equation
      modeling to test whether socioeconomic status interacted with latent genetic and
      environmental effects for antisocial behavior. RESULTS: Genetic influences on
      antisocial behavior were more important in adolescents in socioeconomically more
      advantaged environments, whereas the shared environment was higher in adolescents
      in socioeconomically less advantaged environments. Heritability for antisocial
      behavior was higher in girls than in boys, irrespective of socioeconomic
      background. CONCLUSIONS: Our results suggest that different intervention policies
      should be considered in different socioeconomic areas. In socioeconomically
      advantaged areas, it might be more fruitful to focus on individually based
      preventions and treatments. In socioeconomically disadvantaged areas,
      intervention and prevention policies might be more effective on a community
      level, to account for shared environmental risk factors.

PMID- 16790009
TI  - Barriers to the identification of children with attention deficit/hyperactivity
      disorder.
AB  - BACKGROUND: In most countries, the majority of children with attention
      deficit/hyperactivity disorder (ADHD) are undiagnosed. In the United Kingdom, a
      major barrier to accessing specialist services is the limited recognition of
      disorders by general practitioners. However, it is unclear whether there are also
      barriers at other stages of the help-seeking process. For children with ADHD,
      this study aims to examine the correlates of the different stages of help
      seeking. METHOD: Children with ADHD (n = 232) were identified from the 1999
      British Child and Adolescent Mental Health Survey. Rates and correlates of
      parental recognition of child mental health problems and contact with services
      for these problems were examined. Children who had used particular types of
      services were compared with those who had not. RESULTS: Most (80%) parents of
      children with ADHD recognise that their child has a problem although few (35%)
      construe this in terms of hyperactivity. The impact of the symptoms on key
      adults, rather than child factors, best predicted parental recognition of
      problems. Most parents had been in contact with education-based professionals but
      few had consulted primary care for these problems or had sought help from
      relevant specialist health services. Parental recognition of problems and
      perceived burden, rather than child factors, were the main correlates of contact
      with services. Parental views that their child has hyperactivity were associated
      with greater severity of symptoms. CONCLUSIONS: The main barrier to care for ADHD
      is the limited presentation of these problems to primary care. The majority of
      parents discuss their concerns with professionals based in education services.
      There is a need for parental education about ADHD and for health service input to
      support education professionals in their contact with concerned parents.

PMID- 16790010
TI  - A long-term outcome study of selective mutism in childhood.
AB  - OBJECTIVE: Controlled study of the long-term outcome of selective mutism (SM) in
      childhood. METHOD: A sample of 33 young adults with SM in childhood and two age-
      and gender-matched comparison groups were studied. The latter comprised 26 young
      adults with anxiety disorders in childhood (ANX) and 30 young adults with no
      psychiatric disorders during childhood. The three groups were compared with
      regard to psychiatric disorder in young adulthood by use of the Composite
      International Diagnostic Interview (CIDI). In addition, the effect of various
      predictors on outcome of SM was studied. RESULTS: The symptoms of SM improved
      considerably in the entire SM sample. However, both SM and ANX had significantly
      higher rates for phobic disorder and any psychiatric disorder than controls at
      outcome. Taciturnity in the family and, by trend, immigrant status and a severity
      indicator of SM had an impact on psychopathology and symptomatic outcome in young
      adulthood. CONCLUSION: This first controlled long-term outcome study of SM
      provides evidence of symptomatic improvement of SM in young adulthood. However, a
      high rate of phobic disorder at outcome points to the fact that SM may be
      regarded as an anxiety disorder variant.

PMID- 16790011
TI  - Truffles: much more than a prized and local fungal delicacy.
AB  - Truffles are hypogeous fungi which live in symbiosis with plant host roots in
      order to accomplish their life cycle. Some species, such as Tuber magnatum Pico,
      the 'white truffle', and Tuber melanosporum Vittad., the 'black truffle', are
      highly appreciated in many countries because of their special taste and smell.
      The great demand for the black and white truffles, the increasing attention
      towards other species of local interest for the rural economy (such as T.
      aestivum) together with a drop in productivity, have stimulated researchers to
      develop projects for a better understanding of the ecology of truffles by
      exploiting the new approaches of environmental microbiology and molecular
      ecology. Specific primers have been developed to identify many morphologically
      similar species, the distribution of T. magnatum has been followed in a selected
      truffle-ground, the phylogeography of T. melanosporum and T. magnatum has been
      traced, and the microorganisms associated with the truffles and their habitats
      have been identified.

PMID- 16790012
TI  - The enhancin-like metalloprotease from the Bacillus cereus group is regulated by
      the pleiotropic transcriptional activator PlcR but is not essential for
      larvicidal activity.
AB  - Bacillus cereus group bacteria produce virulence factors. Many of these are
      regulated by the pleiotropic transcriptional activator PlcR, which is implicated
      in insect virulence. In silico analysis of the B. cereus strain ATCC14579 genome
      showed an enhancin-like gene preceded by a typical PlcR binding sequence. The
      gene is predicted to encode a polypeptide showing 23-25% identity with enhancins
      from several baculoviruses and 31% with that of Yersinia pestis. Viral enhancin
      acts after oral infection and degrades the peritrophic matrix of various
      Lepidopteran larvae. To rule out a possible implication of Bacillus enhancin in
      insect virulence, we sequenced the enhancin gene from the Bacillus thuringiensis
      407-crystal minus strain and investigated its gene regulation and larvicidal
      activity. A typical metalloprotease zinc-binding domain (HEIAH) was detected and
      the gene was named mpbE (metalloprotease bacillus enhancin). An mpbE'-lacZ
      transcriptional fusion demonstrated that mpbE belongs to the PlcR regulon. The
      mpbE mutant was fed to Galleria mellonella larvae, and no significant reduction
      in virulence was observed. However, this may not exclude MpbE from a role in
      pathogenesis.

PMID- 16790013
TI  - Chlamydia pneumoniae infection enhances lectin-like oxidized low-density
      lipoprotein receptor (LOX-1) expression on human endothelial cells.
AB  - Many studies indicate that Chlamydia pneumoniae infection is a crucial risk
      factor in atherogenesis. The most relevant cell type for the pathogenesis is the
      macrophage, which possesses classical scavenger receptors that uptake oxidized
      low-density lipoprotein (LDL). Here, a direct involvement of vascular endothelial
      cells in atherogenesis was examined employing in vitro infection of human
      umbilical vein endothelial cells (HUVEC) with C. pneumoniae. Chlamydia pneumoniae
      infection greatly enhanced the uptake of oxidized LDL, but not of acetylated LDL,
      by HUVEC. Among the scavenger receptors analyzed, LOX-1 transcription, which
      prefers oxidized LDL to acetylated LDL, was significantly amplified.

PMID- 16790014
TI  - Involvement of two related porins, OprD and OpdP, in the uptake of arginine by
      Pseudomonas aeruginosa.
AB  - The OprD family of specific porins in Pseudomonas aeruginosa comprises 19
      members, some of which have been demonstrated to facilitate the uptake of
      specific compounds into the cell. The members of this family share considerable
      amino acid sequence similarity (46-57%), which is unusual among porin molecules.
      In this work, we sought to establish whether this sequence conservation was the
      basis for other shared aspects of this family. The transcriptional profiles of
      eight relatively well-characterized OprD homologs were assessed in cells grown on
      a variety of carbon compounds. The expression of these paralogous proteins
      correlated with their phylogenetic distribution into two subfamilies in that the
      three members of the OpdK subfamily were induced by their specific (organic acid)
      substrates while the five members of the amino-acid/peptide-specific OprD
      subfamily appeared to be constitutively expressed. Functional overlap with
      respect to arginine transport was observed between two members of the latter
      subfamily, the basic amino acid-specific porin, OprD, and the glycine-glutamate
      specific porin, OpdP. The impact of this apparent functional redundancy on the
      genetic fitness of P. aeruginosa is discussed.

PMID- 16790015
TI  - Two pathways of electron transport to nitrogenase in Rhodospirillum rubrum: the
      major pathway is dependent on the fix gene products.
AB  - In the photosynthetic bacterium Rhodospirillum rubrum, as in many other
      diazotrophs, electron transport to nitrogenase has not been characterized in
      great detail. In this study, we show that there are two pathways operating in R.
      rubrum. The products of the fix genes constitute the major pathway operating
      under heterotrophic conditions, whereas a pyruvate:ferredoxin oxidoreductase,
      encoded by the nifJ gene, may play a central role under anaerobic conditions in
      the dark. In both systems, ferredoxin N is the main direct electron donor to
      dinitrogenase reductase. Furthermore, we suggest from studying mutants lacking
      components in one or both systems under different conditions, that the Fix system
      operates most efficiently under conditions when a proton motive force is
      generated. A model for our current view of the electron transfer pathways in R.
      rubrum is presented.

PMID- 16790016
TI  - Acetyl-CoA synthetase from Pseudomonas putida U is the only acyl-CoA activating
      enzyme induced by acetate in this bacterium.
AB  - The gene (acs) encoding the acetyl-CoA synthetase (Acs) in Pseudomonas putida U
      has been cloned, sequenced and expressed in different microbes. The protein has
      been purified and characterized from a biochemical, structural and evolutionary
      point of view. Disruption or deletion of acs handicapped the bacterium for growth
      in a chemically defined medium containing acetate; this ability was regained when
      P. putida U was transformed with a plasmid carrying this gene. By contrast, all
      the acs knock-out mutants could assimilate n-alkanoic acids having a carbon
      length greater than C2, suggesting that other acyl-CoA activating enzymes
      (different from Acs) are involved in the catabolism of these compounds. However,
      these enzymes that can replace the function played by Acs in vivo are not induced
      by acetate.

PMID- 16790017
TI  - PFPI-like genes are expressed in Leishmania major but are pseudogenes in other
      Leishmania species.
AB  - Pyrococcus furiosus protease I (PFPI) is a multimeric cysteine peptidase from P.
      furiosus. Genome analyses indicate that orthologues are present in rather few
      other organisms, including Dictyostelium discoideum and several bacteria, Archaea
      and plants. An open reading frame (ORF) coding for a PFPI-like protein (PFP1) was
      identified in Leishmania major and Leishmania mexicana and full-length spliced
      and polyadenylated PFP1 mRNA detected for both species. Vestiges of a PFPI-like
      gene could also be identified in Leishmania braziliensis and Leishmania infantum,
      but no ORF remains owing to the presence of frame-shifts and stop codons. No
      evidence for a PFPI-like gene could be found in the syntenic region of
      Trypanosoma brucei or Trypanosoma cruzi, raising the possibility that the PFPI
      like genes were acquired by a lateral gene transfer event after the divergence of
      trypanosomes and Leishmania. The gene may have subsequently degenerated into a
      pseudogene in some Leishmania species, owing to the loss of relevant biological
      function. However, antibodies raised against L. mexicana recombinant protein
      detected PFP1 in promastigote extracts of L. major, but not in L. mexicana
      promastigote or amastigote extracts. The expression of PFP1 in L. major suggests
      that PFP1 might contribute to the disease tropism that distinguishes this
      Leishmania species from others.

PMID- 16790018
TI  - Shifts in microbial community functions and nitrifying communities as a result of
      combined application of copper and mefenoxam.
AB  - In this microcosm study, we focused on the effect of a combined application of
      copper and mefenoxam on the functional diversity of soil microbial communities.
      Treatments with combined and separate applications of copper and mefenoxam were
      sampled at 24 and 60 days and control soil was sampled at 0, 24 and 60 days.
      Structural and metabolic profiling of microorganisms were performed by
      arbitrarily primed (AP) and RNA arbitrarily primed-PCR (RAP-PCR). Cluster
      analysis resulted in separate grouping of AP and RAP-PCR profiles, with
      differences between control and treatments being more pronounced with respect to
      RAP-PCR profiles. amoA, a functional molecular marker for beta-subgroup ammonia
      oxidizing bacteria, could only be detected at day 60 in treatments of mefenoxam,
      and mefenoxam+copper, with higher gene copies in the latter. There was also an
      increase in potential nitrification activity on application of mefenoxam and
      mefenoxam+copper. Comparison of amoA diversity was performed by denaturing
      gradient gel electrophoresis followed by construction of a clone library of amoA
      fragments amplified from the mefenoxam+copper-treated sample. Analysis of clones
      was performed by restriction digestion and subsequent sequencing. Patterns 1 and
      5 were seen in 93% of the clones and clustered together with amoA sequences of
      Nitrosospira, indicating that Nitrosospira-like organisms are the major
      nitrifiers under mefenoxam treatments.

PMID- 16790019
TI  - Field distribution of Sorosphaera viticola in commercial vineyards in Germany.
AB  - In the year 2000, resting spores of a previously undescribed plasmodiophorid were
      found in roots of Vitis spp. This plasmodiophorid was identified as a member of
      the genus Sorosphaera Schroeter and described as Sorosphaera viticola Kirchmair,
      Neuhauser, Huber. To attain information on the field distribution of Sorosphaera
      viticola, a selective screening was conducted in two commercial vineyards in
      Germany. A study to determine a correlation of Sorosphaeraviticola infection to
      grapevine growth was also performed.

PMID- 16790020
TI  - Identification of a glycolytic regulon in the archaea Pyrococcus and
      Thermococcus.
AB  - The glycolytic pathway of the hyperthermophilic archaea that belong to the order
      Thermococcales (Pyrococcus, Thermococcus and Palaeococcus) differs significantly
      from the canonical Embden-Meyerhof pathway in bacteria and eukarya. This archaeal
      glycolysis variant consists of several novel enzymes, some of which catalyze
      unique conversions. Moreover, the enzymes appear not to be regulated
      allosterically, but rather at transcriptional level. To elucidate details of the
      gene expression control, the transcription initiation sites of the glycolytic
      genes in Pyrococcus furiosus have been mapped by primer extension analysis and
      the obtained promoter sequences have been compared with upstream regions of non
      glycolytic genes. Apart from consensus sequences for the general transcription
      factors (TATA-box and BRE) this analysis revealed the presence of a potential
      transcription factor binding site (TATCAC-N(5)-GTGATA) in glycolytic and starch
      utilizing promoters of P. furiosus and several thermococcal species. The absence
      of this inverted repeat in Pyrococcus abyssi and Pyrococcus horikoshii probably
      reflects that their reduced catabolic capacity does not require this regulatory
      system. Moreover, this phyletic pattern revealed a TrmB-like regulator (PF0124
      and TK1769) which may be involved in recognizing the repeat. This Thermococcales
      glycolytic regulon, with more than 20 genes, is the largest regulon that has yet
      been described for Archaea.

PMID- 16790022
TI  - Histamine, histidine, and growth-phase mediated regulation of the histidine
      decarboxylase gene in lactic acid bacteria isolated from wine.
AB  - Fermented foods are frequently contaminated by histamine that is generated by
      microorganisms with histidine decarboxylase activity. The ingestion of large
      amounts of histamine can cause serious toxicological problems in humans. A study
      of the effects of histamine, histidine, and growth phase on histamine production
      by lactic acid bacteria isolated from wine is reported here. With northern blots
      and specific activity analysis, we observed that histidine induces the expression
      of the histidine decarboxylase gene (hdc) and that histamine causes a decrease in
      the expression of this gene. The expression of hdc is also mediated by the
      bacterial growth phase. Histidine and histamine do not affect histidine
      decarboxylase activity, whereas pyridoxal 5'-phosphate does. Data on histamine
      producing lactic acid bacteria isolated from wine should contribute to the
      prevention of histamine formation during winemaking and storage.

PMID- 16790021
TI  - Spontaneous resistance in Lactococcus lactis IL1403 to the lantibiotic lacticin
      3147.
AB  - The ability and frequency at which target organisms can develop resistance to
      bacteriocins is a crucial consideration in designing and implementing bacteriocin
      based biocontrol strategies. Lactococcus lactis ssp. lactis IL1403 was used as a
      target strain in an attempt to determine the frequency at which spontaneously
      resistant mutants are likely to emerge to the lantibiotic lacticin 3147.
      Following a single exposure to lacticin 3147, resistant mutants only emerged at a
      low frequency (10(-8)-10(-9)) and were only able to withstand low levels of the
      bacteriocin (100 AU mL(-1)). However, exposure to increasing concentrations, in a
      stepwise manner, resulted in the isolation of eight mutants that were resistant
      to moderately higher levels of lacticin 3147 (up to 600 AU mL(-1)).
      Interestingly, in a number of cases cross-resistance to other lantibiotics such
      as nisin and lacticin 481 was observed, as was cross-resistance to environmental
      stresses such as salt. Finally, reduced adsorption of the bacteriocin in to the
      cell was documented for all resistant mutants.

PMID- 16790023
TI  - Characterization of a novel cyclomaltodextrinase expressed from environmental DNA
      isolated from Bor Khleung hot spring in Thailand.
AB  - A novel gene belonging to the alpha-amylase family was isolated directly from
      community DNA obtained from soil sediments collected from Bor Khleung hot spring
      in Thailand. Partial sequences harboring four conserved regions of the alpha
      amylase family were amplified by PCR using degenerate primers. Upstream and
      downstream sequences of these fragments were obtained by a genome walking
      approach to identify a full-length gene (Env cda13A) encoding 619 amino acids.
      Amino acid sequence alignments of Env Cda13A with other enzymes suggested that
      this enzyme was a cyclomaltodextrinase. The Env cda13A gene was expressed in
      Pichia pastoris as a secreted functional protein of 68 kDa. The partially
      purified enzyme was shown to be monomeric and hydrolyzed various maltodextrins
      from maltotriose to maltoheptaose and cyclomaltodextrins to give maltose and
      glucose as the main products. The enzyme also hydrolyzed pullulan and soluble
      starch to yield glucose, but the rate of hydrolysis was slow. This study
      demonstrated the possibility of isolating potentially novel enzymes directly from
      natural environments and opens an unexplored biodiversity resource in Thailand
      for future novel gene discoveries.

PMID- 16790024
TI  - Cell structure degradation in Escherichia coli and Thermococcus sp. strain Tc-1
      95 associated with thermal death resulting from brief heat treatment.
AB  - The thermal death mechanism of microorganisms when heated at lethally high
      temperatures is still not fully understood. In this study, we examined the
      relationship between thermal death and degradation of the cell structure in the
      mesophilic bacterium Escherichia coli strain W3110 and the hyperthermophilic
      archaeon Thermococcus sp. strain Tc-1-95. By heating the microorganisms at
      lethally high temperatures only briefly (1.5 s duration) in a flow-type
      apparatus, we studied the microbial cells at very early and critical stages of
      the thermal death process. For E. coli, it was found that the loss of viability
      was not associated with thermal damage to the cell envelope. Deformation of the
      nucleoid was observed. These results suggest that the thermal death of E. coli is
      attributed to thermal denaturation or degradation of cytoplasmic molecules. On
      the other hand, the thermal death of Thermococcus sp. strain Tc-1-95 was strongly
      associated with rupture of the cell envelope. Furthermore, massive deformation of
      the S-layer with lethal thermal stress was observed. These results demonstrate
      that the thermal deaths of the two microorganisms investigated proceed via very
      different mechanisms. The contrast can be attributed to the difference in their
      cell envelope structures.

PMID- 16790025
TI  - Effect of the morphogene bolA on the permeability of the Escherichia coli outer
      membrane.
AB  - Escherichia coli bolA is a morphogene involved in stress response and cell
      division. Overexpression of bolA induces biofilm formation and affects the levels
      of carboxypeptidases PBP5, PBP6 and beta-lactamase AmpC. In this study, we have
      shown that changes in the expression of bolA result in alterations in the
      properties of the outer membrane. The sensitivity to detergents and vancomycin
      was reduced when bolA was overexpressed and fluorescent probes indicated that
      different levels of bolA had an effect on outer membrane protein accessibility.
      Moreover, bolA was shown to be involved in the modulation of the OmpF/OmpC
      balance.

PMID- 16790026
TI  - Thiobarbituric acid reactive substances, Fe3+ reduction and enzymatic activities
      in cultures of Ganoderma australe growing on Drimys winteri wood.
AB  - Ganoderma australe is a basidiomycete responsible for a natural process of
      selective and extensive lignin degradation. Fatty acids, thiobarbituric acid
      reactive substances (TBARS), Fe3+-reduction and enzymatic activities were
      monitored in cultures of G. australe growing on Drimys winteri wood chips.
      Linoleic acid was de novo synthesized, and steadily increased during 12 weeks of
      cultivation. Part of the unsaturated fatty acids underwent peroxidation as TBARS
      accumulated with biodegradation time. TBARS accumulation was proportional to the
      wood weight and component losses. Manganese-dependent peroxidase and lignin
      peroxidase were not detected in the culture extracts, whereas laccase-induced
      oxidation of syringaldazine peaked after 2 weeks (104+/-9 micromol oxidized min(
      1) kg(-1) of dry wood), subsequently decreasing. On the other hand, nonenzymatic
      Fe3+-reducing activity increased as a function of cultivation time and could be
      involved in the initiation of lipid peroxidation.

PMID- 16790027
TI  - Broad-spectrum antimicrobial activity and high stability of Trichokonins from
      Trichoderma koningii SMF2 against plant pathogens.
AB  - Antimicrobial metabolites produced by Trichoderma koningii SMF2 exhibited
      antimicrobial activity against a range of Gram-positive bacterial and fungal
      phytopathogens. Purification of these metabolites was achieved using combinations
      of gel filtration and high-performance liquid chromatography. Identified by
      liquid chromatography electrospray ionization tandem mass spectrometry, the
      active metabolites proved to be three known peptaibols: Trichokonin VI, VII and
      VIII. The Trichokonins were stable and remained biological active over a wide pH
      range and at every temperature tested, showing no loss of activity even after
      autoclaving. Trichokonins were insensitive to proteolytic enzymes. Trichokonin VI
      takes on typical helical structure and the structure changes only slightly at
      different temperatures and pH values. The present study presented the potential
      of Trichokonins to be used as biological control agents.

PMID- 16790028
TI  - Age-related effects of the neuromodulator D-serine on neurotransmission and
      synaptic potentiation in the CA1 hippocampal area of the rat.
AB  - The effects of the co-agonist of the N-methyl-D-aspartate receptor (NMDAr) D
      serine on glutamatergic neurotransmission and synaptic potentiation were studied
      in the CA1 hippocampal field of young (3-5 months old) and aged (25-27 months
      old) Sprague-Dawley rats using ex vivo extracellular electrophysiological
      recording techniques. Exogenous d-serine depressed fast neurotransmission
      mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate
      subtype of glutamate receptors in young but not in aged rats by acting on
      inhibitory glycinergic interneurons. In contrast, D-serine dose-dependently
      enhanced NMDAr-mediated synaptic responses in both groups of animals, but with a
      larger magnitude in aged rats, thus preventing the age-related decrease in NMDAr
      activation. D-serine also increased the magnitude of long-term potentiation in
      aged but not in young rats. Finally, D-serine levels were dramatically reduced in
      hippocampal tissues of aged rats. Taken together, these results indicate a weaker
      activation of the NMDAr glycine modulatory site by endogenous D-serine in aged
      animals, which accounts for a reduced NMDAr contribution to synaptic plasticity
      in ageing.

PMID- 16790029
TI  - The role of EDS1 (enhanced disease susceptibility) during singlet oxygen-mediated
      stress responses of Arabidopsis.
AB  - Upon a dark/light shift the conditional flu mutant of Arabidopsis starts to
      generate singlet oxygen (1O2) that is restricted to the plastid compartment.
      Distinct sets of genes are activated that are different from those induced by
      hydrogen peroxide/superoxide. One of the genes that is rapidly upregulated is
      EDS1 (enhanced disease susceptibility). The EDS1 protein has been shown to be
      required for the resistance to biotrophic pathogens and the accumulation of
      salicylic acid (SA) that enhances the defenses of a plant by inducing the
      synthesis of pathogen-related (PR) proteins. Because of the similarity of its N
      terminal portion to the catalytic site of lipases, EDS1 has also been implicated
      with the release of polyunsaturated fatty acids and the subsequent formation of
      various oxylipins. The release of singlet oxygen in the flu mutant triggers a
      drastic increase in the concentration of free SA and activates the expression of
      PR1 and PR5 genes. These changes depend on the activity of EDS1 and are
      suppressed in flu/eds1 double mutants. Soon after the beginning of singlet oxygen
      production, the synthesis of oxylipins such as jasmonic acid (JA) and 12
      oxophytodienoic acid (OPDA) also start and plants stop growing and induce a cell
      death response. The inactivation of EDS1 does not affect oxylipin synthesis,
      growth inhibition and the initiation of cell death, but it does allow plants to
      recover much faster from singlet oxygen-mediated growth inhibition and it also
      suppresses the spread of necrotic lesions in leaves. Hence, singlet oxygen
      activates a complex stress-response program with EDS1 playing a key role in
      initiating and modulating several steps of it. This program includes not only
      responses to oxidative stress, but also responses known to be activated during
      plant-pathogen interactions and wounding.

PMID- 16790030
TI  - An evolutionarily conserved translation initiation mechanism regulates nuclear or
      mitochondrial targeting of DNA ligase 1 in Arabidopsis thaliana.
AB  - The Arabidopsis DNA ligase 1 gene (AtLIG1) is indispensable for cell viability.
      AtLIG1 expresses one major and two minor mRNA transcripts differing only in the
      length of the 5' untranslated leader sequences preceding a common ORF. Control of
      AtLIG1 isoform production and intracellular targeting depends upon mechanisms
      controlling the choice of translation initiation site within the AtLIG1 ORF.
      Confocal laser scanning microscopy of green fluorescent protein-tagged AtLIG1
      isoforms expressed in Arabidopsis revealed that translation of AtLIG1 mRNA
      transcripts from the first in-frame start codon produces an AtLIG1 isoform that
      is targeted exclusively to the mitochondria. Translation initiation from the
      second in-frame start codon produces an AtLIG1 isoform targeted only to the
      nucleus. There is no evidence for AtLIG1-GFP being targeted to chloroplasts. The
      mitochondrial AtLIG1 isoform possesses both an N-terminal mitochondrial-targeting
      signal and an internal bipartite nuclear localization signal (NLS) yet is
      targeted only to mitochondria, demonstrating a hierarchical dominance of the
      mitochondrial presequence over the NLS. The length of the 5'-UTR and more
      significantly the nucleotide context around alternative start codons in the
      AtLIG1 transcripts affect translation initiation to ensure a balanced synthesis
      of both nuclear and mitochondrial AtLIG1 isoforms, probably via a context
      dependent leaky ribosome scanning mechanism.

PMID- 16790031
TI  - Involvement of wound-induced receptor-like protein kinase in wound signal
      transduction in tobacco plants.
AB  - The wound-induced receptor-like protein kinase (WRK) gene, isolated as one of the
      genes whose transcripts accumulated during the early period of N gene-dependent
      synchronized cell death in tobacco mosaic virus-infected tobacco plants, encodes
      a leucine-rich repeat receptor-like protein kinase, and its transcript was
      transiently increased 15 min after wounding. In the present study, analysis of a
      green fluorescent protein fusion protein indicated that WRK is localized in the
      plasma membrane. In transgenic tobacco plant lines with elevated or suppressed
      levels of WRK transcript, the wound-induced accumulation of both basic PR-1 and
      PR-6 transcripts was slightly enhanced or significantly suppressed respectively.
      The decrease in wound-induced basic PR gene expression in WRK suppressed lines
      was restored by jasmonic acid (JA) treatment. Furthermore, the levels of wound
      induced enzymatic activation of both salicylic acid-induced protein kinase (SIPK)
      and wound-induced protein kinase (WIPK) and wound-induced accumulation of JA were
      reduced in the WRK suppressed lines in comparison with a control line. These
      results suggest that WRK functions upstream of SIPK and WIPK and regulates wound
      signal transduction in tobacco plants.

PMID- 16790032
TI  - Clinically confirmed type 2 diabetes mellitus and colorectal cancer risk: a
      population-based, retrospective cohort study.
AB  - OBJECTIVES: Patients with type 2 diabetes mellitus (DM) may be at increased
      colorectal cancer (CRC) risk. However, existing data are inconsistent. We
      investigated CRC risks, overall and by anatomic subsite, within a population
      based inception cohort of clinically confirmed type 2 DM subjects. METHODS: All
      residents of Rochester, Minnesota who first met standardized criteria for type 2
      DM from 1970 to 1994 (997 men and 978 women) were identified and followed forward
      in time until emigration, death, or December 31, 1999. Incident CRC cases were
      identified by review of inpatient and outpatient medical records. Standardized
      incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated to
      compare CRC incidence within the type 2 DM inception cohort with previously
      published rates for the Rochester general population. RESULTS: Over 19,158 person
      years of follow-up, 51 incident CRC cases were identified within the type 2 DM
      cohort, while only 36.8 cases were expected (SIR = 1.39, 95% CI 1.03-1.82). Among
      men, type 2 DM was associated with increased overall (SIR = 1.67, 95% CI 1.16
      2.33) and proximal (SIR = 1.96, 95% CI 1.16-3.10) CRC risks; distal CRC risk was
      also increased, but the point estimate was not statistically significant (SIR =
      1.43, 95% CI 0.82-2.32). Among women, type 2 DM was not a risk factor for
      overall, proximal, or distal CRC (SIR = 1.03, 95% CI 0.60-1.66; SIR = 1.17, 95%
      CI 0.58-2.09; and SIR = 0.74, 95% CI 0.24-1.72, respectively). Within the type 2
      DM cohort, current and former cigarette smokers were at higher CRC risk (SIR =
      1.77, 95% CI 1.24-2.47) than never smokers (SIR = 0.99, 95% CI 0.57-1.61) and the
      interaction between type 2 DM and cigarette smoking status was statistically
      significant (p= 0.05). CONCLUSIONS: In this population-based, retrospective
      cohort study, clinically confirmed type 2 DM was associated with increased CRC
      risk, predominantly among men. Cigarette smoking appeared to positively modify DM
      associated CRC risk, which to our knowledge has not been previously reported.
      These data suggest that further investigation of potential interactions between
      endogenous and exogenous factors involved in colorectal carcinogenesis may help
      to clarify the magnitude and extent of CRC risk experienced by persons with type
      2 DM.

PMID- 16790033
TI  - The inflammatory C-reactive protein is increased in both liver and adipose tissue
      in severely obese patients independently from metabolic syndrome, Type 2
      diabetes, and NASH.
AB  - OBJECTIVE: C-Reactive Protein (CRP), a nonspecific marker of inflammation that is
      moderately elevated in obesity, metabolic syndrome (MS), and type 2 diabetes, has
      been proposed as a surrogate marker of nonalcoholic steatohepatitis (NASH). Its
      clinical usefulness in the diagnosis of NASH was evaluated in severely obese
      patients without or with MS, diabetes, and NASH and the potential roles of the
      liver and of the adipose tissue in CRP production were characterized. METHODS:
      Severely obese patients without NASH (without MS [N = 13], with MS [N = 11], or
      with MS and diabetes [N = 7]) and with NASH (without [N = 8] or with [N = 7] MS)
      were studied. For each patient, liver and adipose tissue biopsies were collected
      during a bariatric surgery and were used to determine the CRP gene expression by
      real-time PCR. The role of interleukin-6 (IL6) and lipopolysaccharide in CRP
      expression was also evaluated in subcutaneous adipose tissue obtained during
      cosmetic abdominoplasty. RESULTS: Plasma CRP levels were elevated in severely
      obese patients independently from the presence or absence of MS, diabetes, or
      NASH. CRP gene expression was not only increased in livers but also in adipose
      tissues of obese patients compared with controls subjects. In human adipose
      tissue, CRP mRNA levels were positively correlated with those of IL-6 and the CRP
      expression was enhanced in vitro by IL-6 and lipopolysaccharide. CONCLUSION:
      Plasma CRP levels are not predictive of the diagnosis of NASH in severely obese
      patients. The liver but also the adipose tissue can produce CRP, a process which
      could be dependent on IL6. Therefore, both tissues might contribute to the
      elevated plasma CRP levels found in obesity. In addition, the large amount of
      body fat may well produce an important part of the circulating CRP, further
      limiting its clinical usefulness in the evaluation of NASH in severely obese
      patients.

PMID- 16790034
TI  - More advanced hepatic fibrosis in hispanics with chronic hepatitis C infection:
      role of patient demographics, hepatic necroinflammation, and steatosis.
AB  - BACKGROUND AND AIMS: We sought to assess whether Hispanics have more advanced
      hepatitis C virus (HCV)-related liver disease than non-Hispanic whites (NHW) and
      to identify contributory factors. PATIENTS AND METHODS: Patients were recruited
      from the Los Angeles county hepatitis clinic. Liver fibrosis and
      necroinflammation (NI) were assessed by the Ishak scoring system. Hepatic
      steatosis was graded as 0-4. RESULTS: A total of 232 patients were evaluated, 63
      NHW and 169 Hispanic. Hispanics were older and had a higher prevalence of blood
      transfusion (40%vs 21%), obesity (body mass index > 30) (47%vs 21%), diabetes
      mellitus (DM) (16%vs 5%), and hepatic steatosis (79%vs 47%), p < 0.02.
      Independent predictors of hepatic steatosis were Hispanic ethnicity (odds ratio
      [OR] 3.8, 95% CI 1.7-8.7, p= 0.001) and obesity (OR 5.7, 95% CI 2.3-14.1, p=
      0.0002). Compared with NHW, Hispanics also had higher fibrosis stage (3.3 +/- 2
      vs 2.3 +/- 6.9, p= 0.001), NI grade (6.4 +/- 1.8 vs 5.6 +/- 1.6, p= 0.002), and
      faster fibrosis progression/yr (0.14 +/- 0.09 vs 0.09 +/- 0.07, p= 0.0002).
      Presence of DM (OR 2.9, p= 0.02), grade 1-2 hepatic steatosis (OR 2.3, p= 0.03),
      AST/ALT > 1 (OR 4.3, p= 0.01), NI grade (OR 1.7, p < 0.0001), age at biopsy (OR
      1.1, p < 0.0001), and serum bilirubin (OR 5.4, p < 0.0001) were independent
      predictors of fibrosis stage > or =4. CONCLUSION: This study confirms that
      Hispanics have more advanced hepatic fibrosis than NHW. This is related to older
      age, higher NI grade, and greater prevalence of hepatic steatosis and DM.

PMID- 16790035
TI  - Detection of unsuspected left hepatic lobe metastases during EUS staging of
      cancer of the esophagus and cardia.
AB  - BACKGROUND: High resolution imaging of the left hepatic lobe can be obtained via
      endoscopic ultrasound (EUS), allowing for detection of unsuspected metastatic
      disease during cancer staging. The frequency at which occult liver metastases are
      detected during EUS staging of cancer of the esophagus and cardia is unknown.
      METHODS: Over an 18-month period, 98 patients underwent EUS staging for a new
      diagnosis of cancer of the esophagus and cardia. Wire-guided dilation was
      performed if necessary. Standard radial examination was followed by curvilinear
      evaluation with attention to the left hepatic lobe. All suspicious liver lesions
      were aspirated under EUS guidance. RESULTS: The radial and curvilinear
      echoendoscope were successfully passed to the antrum in 86% and 81% of cases,
      respectively, without complication. Thirty-two percent of patients required
      dilation. Lesions suspicious for left hepatic lobe metastases were found in 7% of
      cases that could be completely evaluated by EUS, all of which underwent EUS
      guided fine needle aspiration. All lesions were proven metastases: four true
      positive and one false-negative cytologic result. CONCLUSION: Curvilinear EUS
      examination of the left hepatic lobe in addition to standard radial EUS
      examination can be performed safely when staging cancer of the esophagus and
      cardia. Dedicated left hepatic lobe examination should be performed as it avoids
      unnecessary surgery in a subset of these patients by detection of occult liver
      metastases.

PMID- 16790036
TI  - Type 2 diabetes mellitus: the impact on colorectal adenoma risk in women.
AB  - OBJECTIVES: Increased risk for colorectal cancer (CRC) has been associated with
      type 2 diabetes. Despite several studies linking insulin resistance to increased
      CRC risk, there are limited data on colorectal adenoma risk in diabetic women. We
      hypothesized that diabetic women would have increased rates of colorectal
      adenomas relative to a group of nondiabetic women. METHODS: Colorectal adenoma
      rates were determined in 100 estrogen-negative women with type 2 diabetes
      mellitus and compared with 500 nondiabetic, estrogen-negative controls. Adenomas
      were defined as any adenoma or advanced adenoma (villous or tubulovillous
      features, size >1 cm or high-grade dysplasia). A multivariate model including
      age, race, diabetes, hypertension, hypercholesterolemia, body mass index, and
      nonsteroidal anti-inflammatory drug status was used to determine the independent
      effects of diabetes on colorectal adenoma incidence. RESULTS: Diabetics as
      compared with nondiabetics had greater rates of any adenoma (37%vs 24%, p= 0.009)
      and advanced adenomas (14%vs 6%, p= 0.009). Two hundred forty-five obese subjects
      compared with 355 nonobese subjects had a higher rate of any adenoma (32%vs 22%,
      p= 0.001). Obese diabetics compared with nonobese, nondiabetics had greater rates
      of any adenoma (42%vs 23%, p< or = 0.001) and advanced adenomas (19%vs 7%, p< or
      = 0.001). Multivariate analysis showed that adenomas and advanced adenomas were
      independently predicted by diabetes (p < 0.05) and adenomas by age. DISCUSSION:
      Women with type 2 diabetes mellitus had higher rates of colorectal adenomas as
      compared with lean and nondiabetic women. This finding adds to the evidence that
      type 2 diabetes is an important factor in the progression of the adenoma
      carcinoma sequence.

PMID- 16790037
TI  - Five cases of de novo inflammatory bowel disease after orthotopic liver
      transplantation.
AB  - Immunosuppression is currently the treatment of choice for severe inflammatory
      bowel disease (IBD). Thus, it was anticipated that the course of preexisting IBD
      should improve after orthotopic liver transplantation (OLT). Despite sufficient
      allograft immunosuppressive therapy, however, exacerbation of IBD or the
      development of de novo IBD after OLT were described in some cases, primarily in
      patients transplanted for end-stage primary sclerosing cholangitis (PSC). In
      addition, the development of de novo IBD in patients undergoing OLT for
      indications other than PSC was described. Evaluating our collective of 314 liver
      transplanted patients we found five patients transplanted for various indications
      other than PSC (autoimmune hepatitis [AIH], acute-on-chronic hepatitis B,
      Wilson's disease, and cryptogenic cirrhosis) who developed de novo IBD after OLT
      despite sufficient immunosuppressive therapy with tacrolimus or cyclosporine. PSC
      was widely excluded in these patients by clinical and histological examinations
      and there was no sign of an enteric infection. It was remarkable that all
      patients were suspected to have an autoimmune background. Four of our patients
      were women and almost all patients showed histologically typical signs of an
      ulcerative colitis (UC). To prevent allograft rejection, three of five patients
      were treated with cyclosporine and the other two with tacrolimus. After
      diagnosis, treatment with aminosalicylates and corticosteroids led to complete
      clinical and histological remission. However, relapses occurred frequently after
      termination of specific therapy. In combination with previous reports, our cases
      indicate an immune dysregulation leading to the development of de novo IBD after
      OLT under immunosuppressive therapy. Reviewing the literature, it should be
      considered that apart from the autoimmune background, immunosuppressive therapy
      may itself play a major role in the development of de novo IBD. From the clinical
      point of view, it is of critical importance to detect this phenomenon, since
      diarrhea is an important cause of morbidity and mortality in transplanted
      patients and therapy for this disorder completely differs from the treatment for
      other causes of diarrhea. Aminosalicylates and courses of corticosteroids offer
      an effective treatment.

PMID- 16790038
TI  - CRASH2 in Germany [ISRCTN86750102].

PMID- 16790039
TI  - Effectiveness and cost-effectiveness of a minimal psychological intervention to
      reduce non-severe depression in chronically ill elderly patients: the design of a
      randomised controlled trial [ISRCTN92331982].
AB  - BACKGROUND: Depression is a prevalent disorder in chronically ill elderly
      persons. It may decrease quality of life, and increase functional disability,
      medical costs, and healthcare utilisation. Because patients may slip into a
      downward spiral, early recognition and treatment of depression is important.
      Depression can be treated with antidepressants or psychological interventions;
      the latter can also be applied by trained paraprofessionals. In this paper, we
      describe the design of the DELTA study (Depression in Elderly with Long-Term
      Afflictions). The first objective of the DELTA study is to evaluate the
      effectiveness and cost-effectiveness of a minimal psychological intervention
      (MPI) to reduce depression in chronically ill elderly patients. The second
      objective is to evaluate whether a potential effect of the MPI may differ between
      types of chronic illnesses. The tailor-made intervention is administered by
      nurses, who are trained in the principles of cognitive behavioural therapy and
      self-management. METHODS/DESIGN: DELTA is a two-armed randomised controlled
      trial, comparing MPI to usual care. A total number of 180 patients with diabetes
      mellitus type II (DM) and 180 patients with chronic obstructive pulmonary disease
      (COPD), who in addition suffer from non-severe depression, will be included in
      the study. In our study, non-severe depression is defined as having minor
      depression, mild major depression or moderate major depression. The primary
      outcome measure is depression using the Beck Depression Inventory. Secondary
      outcome measures include quality of life, daily functioning, self-efficacy,
      autonomy, and participation. In the economic evaluation, cost-effectiveness and
      cost-utility ratios will be calculated. Furthermore, a process evaluation will be
      carried out. Analyses will include both univariate and multivariate techniques
      and according to the intention to treat principle. The economic evaluation will
      be done from a societal perspective and data of the process evaluation will be
      analysed using descriptive techniques. DISCUSSION: A total number of 361 patients
      has been included in the study. All interventions have been administered and
      follow-up data will be complete in September 2006. Preliminary results from the
      process evaluation indicate that patients' satisfaction with the intervention is
      high. If this intervention proves to be effective, implementation of the DELTA
      intervention is considered and anticipated.

PMID- 16790041
TI  - Docking protein domains in contact space.
AB  - BACKGROUND: Many biological processes involve the physical interaction between
      protein domains. Understanding these functional associations requires knowledge
      of the molecular structure. Experimental investigations though present
      considerable difficulties and there is therefore a need for accurate and reliable
      computational methods. In this paper we present a novel method that seeks to dock
      protein domains using a contact map representation. Rather than providing a full
      three dimensional model of the complex, the method predicts contacting residues
      across the interface. We use a scoring function that combines structural,
      physicochemical and evolutionary information, where each potential residue
      contact is assigned a value according to the scoring function and the hypothesis
      is that the real configuration of contacts is the one that maximizes the score.
      The search is performed with a simulated annealing algorithm directly in contact
      space. RESULTS: We have tested the method on interacting domain pairs that are
      part of the same protein (intra-molecular domains). We show that it correctly
      predicts some contacts and that predicted residues tend to be significantly
      closer to each other than other pairs of residues in the same domains. Moreover
      we find that predicted contacts can often discriminate the best model (or the
      native structure, if present) among a set of optimal solutions generated by a
      standard docking procedure. CONCLUSION: Contact docking appears feasible and able
      to complement other computational methods for the prediction of protein-protein
      interactions. With respect to more standard docking algorithms it might be more
      suitable to handle protein conformational changes and to predict complexes
      starting from protein models.

PMID- 16790040
TI  - Gene expression profiling of Spodoptera frugiperda hemocytes and fat body using
      cDNA microarray reveals polydnavirus-associated variations in lepidopteran host
      genes transcript levels.
AB  - BACKGROUND: Genomic approaches provide unique opportunities to study interactions
      of insects with their pathogens. We developed a cDNA microarray to analyze the
      gene transcription profile of the lepidopteran pest Spodoptera frugiperda in
      response to injection of the polydnavirus HdIV associated with the ichneumonid
      wasp Hyposoter didymator. Polydnaviruses are associated with parasitic
      ichneumonoid wasps and are required for their development within the lepidopteran
      host, in which they act as potent immunosuppressive pathogens. In this study, we
      analyzed transcriptional variations in the two main effectors of the insect
      immune response, the hemocytes and the fat body, after injection of filter
      purified HdIV. RESULTS: Results show that 24 hours post-injection, about 4% of
      the 1750 arrayed host genes display changes in their transcript levels with a
      large proportion (76%) showing a decrease. As a comparison, in S. frugiperda fat
      body, after injection of the pathogenic JcDNV densovirus, 8 genes display
      significant changes in their transcript level. They differ from the 7 affected by
      HdIV and, as opposed to HdIV injection, are all up-regulated. Interestingly,
      several of the genes that are modulated by HdIV injection have been shown to be
      involved in lepidopteran innate immunity. Levels of transcripts related to
      calreticulin, prophenoloxidase-activating enzyme, immulectin-2 and a novel
      lepidopteran scavenger receptor are decreased in hemocytes of HdIV-injected
      caterpillars. This was confirmed by quantitative RT-PCR analysis but not observed
      after injection of heat-inactivated HdIV. Conversely, an increased level of
      transcripts was found for a galactose-binding lectin and, surprisingly, for the
      prophenoloxidase subunits. The results obtained suggest that HdIV injection
      affects transcript levels of genes encoding different components of the host
      immune response (non-self recognition, humoral and cellular responses).
      CONCLUSION: This analysis of the host-polydnavirus interactions by a microarray
      approach indicates that the presence of HdIV induces, directly or indirectly,
      variations in transcript levels of specific host genes, changes that could be
      responsible in part for the alterations observed in the parasitized host
      physiology. Development of such global approaches will allow a better
      understanding of the strategies employed by parasites to manipulate their host
      physiology, and will permit the identification of potential targets of the
      immunosuppressive polydnaviruses.

PMID- 16790042
TI  - An ELISA-based procedure for assaying proteins in digests of human leukocytes and
      cell lines, using specifically selected peptides and appropriate antibodies.
AB  - BACKGROUND: We describe the application of an ELISA-based assay (the
      Peptidomatrix) that can be used to simultaneously identify and quantitate a
      number of proteins in biological samples. The biological sample (blood component,
      biopsy, culture or other) is first lysed to release all the proteins, without any
      additional separation. The denatured proteins in the sample are then digested in
      bulk with the desired proteolytic enzyme(s). The peptides in the digest are then
      assayed by appropriate antibodies, using a competition ELISA protocol. RESULTS:
      As an example of its use, the present paper applies the Peptidomatrix to the
      assay of four membrane proteins MDR1 (P-glycoprotein or ABCB1), MRP1 (ABCC1),
      BCRP/MXR (ABCG2) and the alpha subunit of the Na, K_ATPase (ATP1A1), present in a
      number of cell lines and in human lymphocytes. We show that we can detect and
      quantitate these proteins, using a series of peptide-antibody pairs, and that we
      can differentiate between cell lines or cell preparations that express the target
      proteins and those that do not. CONCLUSION: We have devised a simple, ELISA-based
      proteomics assay that enables the quantitation of designated proteins in a cell
      or tissue sample, and that can be used in any laboratory, with minimal
      specialized equipment.

PMID- 16790043
TI  - Measles viral load may reflect SSPE disease progression.
AB  - Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive
      neurological disorder caused by the persistent infection with measles virus (MV).
      Despite much research into SSPE, its pathology remains obscure. We examined
      autopsy tissues of eight SSPE patients by real time quantitative PCR,
      immunohistochemistry and immunoblotting to determine viral load. MV N, M and H
      gene RNA could be detected in the central nervous system (CNS) of all patients
      and in two non-CNS tissues of one patient. The viral burden between patients
      differed up to four-fold by quantitative PCR and corresponded with detection of
      MV protein. The level of both viral RNA and antigen in the brain may correlate
      with disease progression.

PMID- 16790044
TI  - Systematic review and meta-analysis of Transurethral Needle Ablation in
      symptomatic Benign Prostatic Hyperplasia.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) constitutes a major clinical
      problem. Minimally invasive therapies for the treatment of symptomatic BPH
      include Transurethral Needle Ablation (TUNA), but it is unclear what impact this
      technique has on the disease and its role among other currently available
      therapeutic options. The objective of this study is to ascertain the efficacy and
      safety of TUNA in the treatment of BPH. METHODS: Systematic review of the
      literature until January 2005 and meta-analysis of clinical studies assessing
      TUNA in symptomatic BPH. Studies were critically appraised. Estimates of effect
      were calculated according to the random-effects model. RESULTS: 35 studies (9
      comparative, 26 non-comparative) were included. Although evidence was limited by
      methodological issues, the analysis of relevant outcomes indicates that while
      TUNA significantly improves BPH parameters with respect to baseline, it does not
      reach the same level of efficacy as TURP in respect to all subjective and
      objective variables. Further, its efficacy declines in the long-term with a rate
      of secondary-treatment significantly higher than of TURP [OR: 7.44 (2.47,
      22.43)]. Conversely, TUNA seems to be a relatively safe technique and shows a
      lower rate of complications than TURP [OR:0.14 (0.05, 0.14)] with differences
      being particularly noteworthy in terms of postoperative bleeding and sexual
      disorders. Likewise, TUNA has fewer anesthetic requirements and generates a
      shorter hospital stay than TURP [WMD: -1.9 days (-2.75, -1.05)]. Scarce data and
      lack of replication of comparisons hinder the assessment of TUNA vs. other local
      therapies. No comparisons with medical treatment were found. CONCLUSION: The body
      of evidence on which TUNA has been introduced into clinical practice is of only
      moderate-low quality. Available evidence suggest that TUNA is a relatively
      effective and safe technique that may eventually prove to have a role in selected
      patients with symptomatic BPH. TUNA significantly improves BPH parameters with
      respect to baseline values, but it does not reach the same level of efficacy and
      long-lasting success as TURP. On the other hand, TUNA seems to be superior to
      TURP in terms of associated morbidity, anesthetic requirements and length of
      hospital stay. With respect to the role of TUNA vis-a-vis other minimally
      invasive therapies, the results of this review indicate that there are
      insufficient data to define this with any degree of accuracy. Overall cost
      effectiveness and the role of TUNA versus medical treatment need further
      evaluation.

PMID- 16790045
TI  - Low carbohydrate diets improve atherogenic dyslipidemia even in the absence of
      weight loss.
AB  - Because of its effect on insulin, carbohydrate restriction is one of the obvious
      dietary choices for weight reduction and diabetes. Such interventions generally
      lead to higher levels of dietary fat than official recommendations and have long
      been criticized because of potential effects on cardiovascular risk although many
      literature reports have shown that they are actually protective even in the
      absence of weight loss. A recent report of Krauss et al. (AJCN, 2006) separates
      the effects of weight loss and carbohydrate restriction. They clearly confirm
      that carbohydrate restriction leads to an improvement in atherogenic lipid states
      in the absence of weight loss or in the presence of higher saturated fat. In
      distinction, low fat diets seem to require weight loss for effective improvement
      in atherogenic dyslipidemia.

PMID- 16790046
TI  - Web-based analysis of the mouse transcriptome using Genevestigator.
AB  - BACKGROUND: Gene function analysis often requires a complex and laborious
      sequence of laboratory and computer-based experiments. Choosing an effective
      experimental design generally results from hypotheses derived from prior
      knowledge or experimentation. Knowledge obtained from meta-analyzing compendia of
      expression data with annotation libraries can provide significant clues in
      understanding gene and network function, resulting in better hypotheses that can
      be tested in the laboratory. DESCRIPTION: Genevestigator is a microarray database
      and analysis system allowing context-driven queries. Simple but powerful tools
      allow biologists with little computational background to retrieve information
      about when, where and how genes are expressed. We manually curated and quality
      controlled 3110 mouse Affymetrix arrays from public repositories. Data queries
      can be run against an annotation library comprising 160 anatomy categories, 12
      developmental stage groups, 80 stimuli, and 182 genetic backgrounds or
      modifications. The quality of results obtained through Genevestigator is
      illustrated by a number of biological scenarios that are substantiated by other
      types of experimentation in the literature. CONCLUSION: The Genevestigator-Mouse
      database effectively provides biologically meaningful results and can be accessed
      at https://www.genevestigator.ethz.ch.

PMID- 16790047
TI  - The tip of the iceberg: a giant pelvic atypical lipoma presenting as a sciatic
      hernia.
AB  - BACKGROUND: This case report highlights two unusual surgical phenomena: lipoma
      like well-differentiated liposarcomas and sciatic hernias. It illustrates the
      need to be aware that hernias may not always simply contain intra-abdominal
      viscera. CASE PRESENTATION: A 36 year old woman presented with an expanding, yet
      reducible, right gluteal mass, indicative of a sciatic hernia. However, magnetic
      resonance imaging demonstrated a large intra- and extra-pelvic fatty mass
      traversing the greater sciatic foramen. The tumour was surgically removed through
      an abdomino-perineal approach. Subsequent pathological examination revealed an
      atypical lipomatous tumour (synonym: lipoma-like well-differentiated
      liposarcoma). The patient remains free from recurrence two years following her
      surgery. CONCLUSION: The presence of a gluteal mass should always suggest the
      possibility of a sciatic hernia. However, in this case, the hernia consisted of
      an atypical lipoma spanning the greater sciatic foramen. Although lipoma-like
      well-differentiated liposarcomas have only a low potential for recurrence, the
      variable nature of fatty tumours demands that patients require regular clinical
      and radiological review.

PMID- 16790049
TI  - Scholarly communications program: force for change.
AB  - The changing landscape of scholarly publication and increasing journal costs have
      resulted in a need for proactive behavior in libraries. At Johns Hopkins
      University in Baltimore, Maryland, a group of librarians joined forces to bring
      these issues to the attention of faculty and to begin a dialog leading to change.
      This commentary describes a comprehensive program undertaken to raise faculty
      awareness of scholarly communications issues. In addition to raising faculty
      interest in the issues at hand, the endeavor also highlights an area where
      library liaisons can increase their communication with the units they serve.

PMID- 16790048
TI  - The features of Drosophila core promoters revealed by statistical analysis.
AB  - BACKGROUND: Experimental investigation of transcription is still a very labor-
      and time-consuming process. Only a few transcription initiation scenarios have
      been studied in detail. The mechanism of interaction between basal machinery and
      promoter, in particular core promoter elements, is not known for the majority of
      identified promoters. In this study, we reveal various transcription initiation
      mechanisms by statistical analysis of 3393 nonredundant Drosophila promoters.
      RESULTS: Using Drosophila-specific position-weight matrices, we identified
      promoters containing TATA box, Initiator, Downstream Promoter Element (DPE), and
      Motif Ten Element (MTE), as well as core elements discovered in Human (TFIIB
      Recognition Element (BRE) and Downstream Core Element (DCE)). Promoters utilizing
      known synergetic combinations of two core elements (TATA_Inr, Inr_MTE, Inr_DPE,
      and DPE_MTE) were identified. We also establish the existence of promoters with
      potentially novel synergetic combinations: TATA_DPE and TATA_MTE. Our analysis
      revealed several motifs with the features of promoter elements, including
      possible novel core promoter element(s). Comparison of Human and Drosophila
      showed consistent percentages of promoters with TATA, Inr, DPE, and synergetic
      combinations thereof, as well as most of the same functional and mutual positions
      of the core elements. No statistical evidence of MTE utilization in Human was
      found. Distinct nucleosome positioning in particular promoter classes was
      revealed. CONCLUSION: We present lists of promoters that potentially utilize the
      aforementioned elements/combinations. The number of these promoters is two orders
      of magnitude larger than the number of promoters in which transcription
      initiation was experimentally studied. The sequences are ready to be
      experimentally tested or used for further statistical analysis. The developed
      approach may be utilized for other species.

PMID- 16790050
TI  - Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a
      transcranial magnetic stimulation study.
AB  - BACKGROUND: The two human cerebral hemispheres are continuously interacting,
      through excitatory and inhibitory influences and one critical structure
      subserving this interhemispheric balance is the corpus callosum. Interhemispheric
      neurophysiological abnormalities and intrahemispheric behavioral impairments have
      been reported in individuals lacking the corpus callosum. The aim of this study
      was to examine intrahemispheric neurophysiological function in primary motor
      cortex devoid of callosal projections. METHODS: Intracortical excitatory and
      inhibitory systems were tested in three individuals with complete agenesis of the
      corpus callosum and sixteen healthy individuals. These systems were assessed
      using transcranial magnetic stimulation (TMS) protocols: motor threshold at rest,
      paired-pulse curve, and cortical silent period. RESULTS: TMS revealed no
      difference between the patient and control groups on the motor threshold measure,
      as well as intracortical facilitation and intracortical inhibition systems as
      tested by paired stimulation. However, intrahemispheric inhibitory function was
      found to be abnormal in participants without callosal projections, as the
      cortical silent period duration was significantly increased in the patient group.
      CONCLUSION: These data suggest that in addition to previously reported impaired
      interhemispheric function, patients lacking the entire corpus callosum also
      display abnormal intrahemispheric excitability of the primary motor cortex.

PMID- 16790051
TI  - An assessment of recently published gene expression data analyses: reporting
      experimental design and statistical factors.
AB  - BACKGROUND: The analysis of large-scale gene expression data is a fundamental
      approach to functional genomics and the identification of potential drug targets.
      Results derived from such studies cannot be trusted unless they are adequately
      designed and reported. The purpose of this study is to assess current practices
      on the reporting of experimental design and statistical analyses in gene
      expression-based studies. METHODS: We reviewed hundreds of MEDLINE-indexed papers
      involving gene expression data analysis, which were published between 2003 and
      2005. These papers were examined on the basis of their reporting of several
      factors, such as sample size, statistical power and software availability.
      RESULTS: Among the examined papers, we concentrated on 293 papers consisting of
      applications and new methodologies. These papers did not report approaches to
      sample size and statistical power estimation. Explicit statements on data
      transformation and descriptions of the normalisation techniques applied prior to
      data analyses (e.g. classification) were not reported in 57 (37.5%) and 104
      (68.4%) of the methodology papers respectively. With regard to papers presenting
      biomedical-relevant applications, 41(29.1 %) of these papers did not report on
      data normalisation and 83 (58.9%) did not describe the normalisation technique
      applied. Clustering-based analysis, the t-test and ANOVA represent the most
      widely applied techniques in microarray data analysis. But remarkably, only 5
      (3.5%) of the application papers included statements or references to assumption
      about variance homogeneity for the application of the t-test and ANOVA. There is
      still a need to promote the reporting of software packages applied or their
      availability. CONCLUSION: Recently-published gene expression data analysis
      studies may lack key information required for properly assessing their design
      quality and potential impact. There is a need for more rigorous reporting of
      important experimental factors such as statistical power and sample size, as well
      as the correct description and justification of statistical methods applied. This
      paper highlights the importance of defining a minimum set of information required
      for reporting on statistical design and analysis of expression data. By improving
      practices of statistical analysis reporting, the scientific community can
      facilitate quality assurance and peer-review processes, as well as the
      reproducibility of results.

PMID- 16790052
TI  - Prediction of catalytic residues using Support Vector Machine with selected
      protein sequence and structural properties.
AB  - BACKGROUND: The number of protein sequences deriving from genome sequencing
      projects is outpacing our knowledge about the function of these proteins. With
      the gap between experimentally characterized and uncharacterized proteins
      continuing to widen, it is necessary to develop new computational methods and
      tools for functional prediction. Knowledge of catalytic sites provides a valuable
      insight into protein function. Although many computational methods have been
      developed to predict catalytic residues and active sites, their accuracy remains
      low, with a significant number of false positives. In this paper, we present a
      novel method for the prediction of catalytic sites, using a carefully selected,
      supervised machine learning algorithm coupled with an optimal discriminative set
      of protein sequence conservation and structural properties. RESULTS: To determine
      the best machine learning algorithm, 26 classifiers in the WEKA software package
      were compared using a benchmarking dataset of 79 enzymes with 254 catalytic
      residues in a 10-fold cross-validation analysis. Each residue of the dataset was
      represented by a set of 24 residue properties previously shown to be of
      functional relevance, as well as a label {+1/-1} to indicate catalytic/non
      catalytic residue. The best-performing algorithm was the Sequential Minimal
      Optimization (SMO) algorithm, which is a Support Vector Machine (SVM). The
      Wrapper Subset Selection algorithm further selected seven of the 24 attributes as
      an optimal subset of residue properties, with sequence conservation, catalytic
      propensities of amino acids, and relative position on protein surface being the
      most important features. CONCLUSION: The SMO algorithm with 7 selected attributes
      correctly predicted 228 of the 254 catalytic residues, with an overall predictive
      accuracy of more than 86%. Missing only 10.2% of the catalytic residues, the
      method captures the fundamental features of catalytic residues and can be used as
      a "catalytic residue filter" to facilitate experimental identification of
      catalytic residues for proteins with known structure but unknown function.

PMID- 16790053
TI  - Randomised controlled trial of welfare rights advice accessed via primary health
      care: pilot study [ISRCTN61522618].
AB  - BACKGROUND: Little research has directly evaluated the impact of increasing
      financial or material resources on health. One way of assessing this lies with
      assisting people to obtain full welfare benefit entitlements. In 2000-1, 2.3
      million pensioners were living in poverty in the UK and estimates suggest that
      around one million do not claim the financial support to which they are entitled.
      The effectiveness of welfare rights advice services delivered via primary health
      care to promote health and reduce health inequalities is unknown. METHODS: The
      main objectives of this study were to assess the feasibility and acceptability of
      a randomised controlled trial of welfare rights advice in a community setting and
      identify appropriate health and social outcome measures in order to plan a
      definitive trial. This was a single blind, community-based, pilot randomised
      controlled trial. 126 men and women aged 60 years and over, recruited from 4
      general practices in Newcastle upon Tyne, UK, participated. The intervention
      comprised a structured welfare rights assessment followed by active assistance
      with welfare benefit claims over the following 24 months. The control group
      received the intervention after a six month delay. A range of socio-economic,
      health, behavioural and psycho-social outcomes were measured. RESULTS: 126 out of
      400 people invited agreed to participate and 109 were followed up at 24 months.
      Both the intervention and research procedures were feasible and acceptable to
      participants and professionals involved. 68 (58%) of all participants received a
      welfare benefit award (31 financial, 16 non-financial and 21 both). Median time
      to receipt of benefits from initial assessment was 14 (range 1 to 78) weeks and
      median financial award was pounds 55 (Euro 81, dollar 98) per household per week.
      There was little evidence of health-related differences between groups or over
      time, which could be due to limitations of the study design. CONCLUSION:
      Modification of the study design, including selection of study participants,
      timing of interventions and length of follow up are recommended for a definitive
      trial. More appropriate health and psycho-social outcome measures relevant to the
      elderly population should be sought, particularly focussing on those issues
      highlighted in the accompanying qualitative study.

PMID- 16790054
TI  - The acceptability and impact of a randomised controlled trial of welfare rights
      advice accessed via primary health care: qualitative study.
AB  - BACKGROUND: Qualitative research is increasingly used alongside randomised
      controlled trials (RCTs) to study a range of factors including participants'
      experiences of a trial. The need for a sound evidence base within public health
      will increase the need for RCTs of non-clinical interventions. Welfare rights
      advice has been proposed as an intervention with potential to reduce health
      inequalities. This qualitative study, nested within an RCT of the impact of
      welfare rights advice, examined the acceptability of the intervention, the
      acceptability of the research process and the perceived impact of the
      intervention. METHODS: 25 men and women aged 60 years or over were recruited from
      four general practices in Newcastle upon Tyne (UK), a sub-sample of those who
      consented to be contacted (n = 96) during the RCT baseline interview. Semi
      structured interviews were undertaken and analysed using the Framework Method.
      RESULTS: Participants viewed the trial positively although, despite agreeing that
      the information leaflet was clear, some had agreed to participate without being
      fully aware of what was involved. Some participants were unaware of the
      implications of randomisation. Most thought it fair, but a few concerns were
      raised about the control condition. The intervention was acceptable and made
      participants feel confident about applying for benefit entitlements. 14 out of 25
      participants received some financial award; median weekly income gain was pounds
      57 (Euro 84, dollar 101). The perceived impact of additional finances was
      considerable and included: increased affordability of necessities and occasional
      expenses; increased capacity to deal with emergencies; and a reduction in stress
      related to financial worries. Overall, perceived independence and ability to
      participate in society increased. Most participants perceived benefits to their
      mental well-being, but no-one reported an improvement in physical health. The RCT
      showed little or no effect on a wide range of outcome measures. CONCLUSION:
      Participation in the trial and the intervention was acceptable to participants.
      Welfare rights advice targeted at people aged 60 years or over and accessed via
      primary care had a positive impact on quality of life and resulted in increased
      social participation. The divergence of qualitative and quantitative findings
      suggests that both methods make important contributions to the evaluation of
      complex social interventions.

PMID- 16790056
TI  - Subfamily logos: visualization of sequence deviations at alignment positions with
      high information content.
AB  - BACKGROUND: Recognition of relevant sequence deviations can be valuable for
      elucidating functional differences between protein subfamilies. Interesting
      residues at highly conserved positions can then be mutated and experimentally
      analyzed. However, identification of such sites is tedious because automated
      approaches are scarce. RESULTS: Subfamily logos visualize subfamily-specific
      sequence deviations. The display is similar to classical sequence logos but
      extends into the negative range. Positive, upright characters correspond to
      residues which are characteristic for the subfamily, negative, upside-down
      characters to residues typical for the remaining sequences. The symbol height is
      adjusted to the information content of the alignment position. Residues which are
      conserved throughout do not appear. CONCLUSION: Subfamily logos provide an
      intuitive display of relevant sequence deviations. The method has proven to be
      valid using a set of 135 aligned aquaporin sequences in which established
      subfamily-specific positions were readily identified by the algorithm.

PMID- 16790055
TI  - The Bacillus anthracis cholesterol-dependent cytolysin, Anthrolysin O, kills
      human neutrophils, monocytes and macrophages.
AB  - BACKGROUND: Bacillus anthracis is an animal and human pathogen whose virulence is
      characterized by lethal and edema toxin, as well as a poly-glutamic acid capsule.
      In addition to these well characterized toxins, B. anthracis secretes several
      proteases and phospholipases, and a newly described toxin of the cholesterol
      dependent cytolysin (CDC) family, Anthrolysin O (ALO). RESULTS: In the present
      studies we show that recombinant ALO (rALO) or native ALO, secreted by viable B.
      anthracis, is lethal to human primary polymorphonuclear leukocytes (PMNs),
      monocytes, monocyte-derived macrophages (MDMs), lymphocytes, THP-1 monocytic
      human cell line and ME-180, Detroit 562, and A549 epithelial cells by trypan blue
      exclusion or lactate dehydrogenase (LDH) release viability assays. ALO
      cytotoxicity is dose and time dependent and susceptibility to ALO-mediated lysis
      differs between cell types. In addition, the viability of monocytes and hMDMs was
      assayed in the presence of vegetative Sterne strains 7702 (ALO+), UT231 (ALO-),
      and a complemented strain expressing ALO, UT231 (pUTE544), and was dependent upon
      the expression of ALO. Cytotoxicity of rALO is seen as low as 0.070 nM in the
      absence of serum. All direct cytotoxic activity is inhibited by the addition of
      cholesterol or serum concentration as low as 10%. CONCLUSION: The lethality of
      rALO and native ALO on human monocytes, neutrophils, macrophages and lymphocytes
      supports the idea that ALO may represent a previously unidentified virulence
      factor of B. anthracis. The study of other factors produced by B. anthracis,
      along with the major anthrax toxins, will lead to a better understanding of this
      bacterium's pathogenesis, as well as provide information for the development of
      antitoxin vaccines for treating and preventing anthrax.

PMID- 16790057
TI  - AgdbNet - antigen sequence database software for bacterial typing.
AB  - BACKGROUND: Bacterial typing schemes based on the sequences of genes encoding
      surface antigens require databases that provide a uniform, curated, and widely
      accepted nomenclature of the variants identified. Due to the differences in
      typing schemes, imposed by the diversity of genes targeted, creating these
      databases has typically required the writing of one-off code to link the database
      to a web interface. Here we describe agdbNet, widely applicable web database
      software that facilitates simultaneous BLAST querying of multiple loci using
      either nucleotide or peptide sequences. RESULTS: Databases are described by XML
      files that are parsed by a Perl CGI script. Each database can have any number of
      loci, which may be defined by nucleotide and/or peptide sequences. The software
      is currently in use on at least five public databases for the typing of Neisseria
      meningitidis, Campylobacter jejuni and Streptococcus equi and can be set up to
      query internal isolate tables or suitably-configured external isolate databases,
      such as those used for multilocus sequence typing. The style of the resulting
      website can be fully configured by modifying stylesheets and through the use of
      customised header and footer files that surround the output of the script.
      CONCLUSION: The software provides a rapid means of setting up customised Internet
      antigen sequence databases. The flexible configuration options enable typing
      schemes with differing requirements to be accommodated.

PMID- 16790059
TI  - 3D-conformal-intensity modulated radiotherapy with compensators for head and neck
      cancer: clinical results of normal tissue sparing.
AB  - BACKGROUND: To investigate the potential of parotic gland sparing of intensity
      modulated radiotherapy (3D-c-IMRT) performed with metallic compensators for head
      and neck cancer in a clinical series by analysis of dose distributions and
      clinical measures. MATERIALS AND METHODS: 39 patients with squamous cell cancer
      of the head and neck irradiated using 3D-c-IMRT were evaluable for dose
      distribution within PTVs and at one parotid gland and 38 patients for toxicity
      analysis. 10 patients were treated primarily, 29 postoperatively, 19 received
      concomitant cis-platin based chemotherapy, 20 3D-c-IMRT alone. Initially the dose
      distribution was calculated with Helax and photon fluence was modulated using
      metallic compensators made of tin-granulate (n = 22). Later the dose distribution
      was calculated with KonRad and fluence was modified by MCP 96 alloy compensators
      (n = 17). Gross tumor/tumor bed (PTV 1) was irradiated up to 60-70 Gy, [5
      fractions/week, single fraction dose: 2.0-2.2 (simultaneously integrated boost)],
      adjuvantly irradiated bilateral cervical lymph nodes (PTV 2) with 48-54 Gy
      [single dose: 1.5-1.8]). Toxicity was scored according the RTOG scale and patient
      reported xerostomia questionnaire (XQ). RESULTS: Mean of the median doses at the
      parotid glands to be spared was 25.9 (16.3-46.8) Gy, for tin granulate 26 Gy, for
      MCP alloy 24.2 Gy. Tin-granulate compensators resulted in a median parotid dose
      above 26 Gy in 10/22, MCP 96 alloy in 0/17 patients. Following acute toxicities
      were seen (degree 0-2/3): xerostomia: 87%/13%, dysphagia: 84%/16%, mucositis:
      89%/11%, dermatitis: 100%/0%. No grade 4 reaction was encountered. During therapy
      the XQ forms showed (degree 0-2/3): 88%/12%. 6 months postRT chronic xerostomia
      degree 0-2/3 was observed in 85%/15% of patients, none with degree 4 xerostomia.
      CONCLUSION: 3D-c-IMRT using metallic compensators along with inverse calculation
      algorithm achieves sufficient parotid gland sparing in virtually all advanced
      head and neck cancers. Since the concept of lower single (and total) doses in the
      adjuvantly treated volumes reduces acute morbidity 3D-c-IMRT nicely meets demands
      of concurrent chemotherapy protocols.

PMID- 16790058
TI  - Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal
      antibody.
AB  - BACKGROUND: To further our understanding of the structure and function of HIV-1
      integrase (IN) we developed and characterized a library of monoclonal antibodies
      (mAbs) directed against this protein. One of these antibodies, mAb33, which is
      specific for the C-terminal domain, was found to inhibit HIV-1 IN processing
      activity in vitro; a corresponding Fv fragment was able to inhibit HIV-1
      integration in vivo. Our subsequent studies, using heteronuclear nuclear magnetic
      resonance spectroscopy, identified six solvent accessible residues on the surface
      of the C-terminal domain that were immobilized upon binding of the antibody,
      which were proposed to comprise the epitope. Here we test this hypothesis by
      measuring the affinity of mAb33 to HIV-1 proteins that contain Ala substitutions
      in each of these positions. To gain additional insight into the mode of
      inhibition we also measured the DNA binding capacity and enzymatic activities of
      the Ala substituted proteins. RESULTS: We found that Ala substitution of any one
      of five of the putative epitope residues, F223, R224, Y226, I267, and I268,
      caused a decrease in the affinity of the mAb33 for HIV-1 IN, confirming the
      prediction from NMR data. Although IN derivatives with Ala substitutions in or
      near the mAb33 epitope exhibited decreased enzymatic activity, none of the
      epitope substitutions compromised DNA binding to full length HIV-1 IN, as
      measured by surface plasmon resonance spectroscopy. Two of these derivatives, IN
      (I276A) and IN (I267A/I268A), exhibited both increased DNA binding affinity and
      uncharacteristic dissociation kinetics; these proteins also exhibited non
      specific nuclease activity. Results from these investigations are discussed in
      the context of current models for how the C-terminal domain interacts with
      substrate DNA. CONCLUSION: It is unlikely that inhibition of HIV-1 IN activity by
      mAb33 is caused by direct interaction with residues that are essential for
      substrate binding. Rather our findings are most consistent with a model whereby
      mAb33 binding distorts or constrains the structure of the C-terminal domain
      and/or blocks substrate binding indirectly. The DNA binding properties and non
      specific nuclease activity of the I267A derivatives suggest that the C-terminal
      domain of IN normally plays an important role in aligning the viral DNA end for
      proper processing.

PMID- 16790060
TI  - Recent developments in biofeedback for neuromotor rehabilitation.
AB  - The original use of biofeedback to train single muscle activity in static
      positions or movement unrelated to function did not correlate well to motor
      function improvements in patients with central nervous system injuries. The
      concept of task-oriented repetitive training suggests that biofeedback therapy
      should be delivered during functionally related dynamic movement to optimize
      motor function improvement. Current, advanced technologies facilitate the design
      of novel biofeedback systems that possess diverse parameters, advanced cue
      display, and sophisticated control systems for use in task-oriented biofeedback.
      In light of these advancements, this article: (1) reviews early biofeedback
      studies and their conclusions; (2) presents recent developments in biofeedback
      technologies and their applications to task-oriented biofeedback interventions;
      and (3) discusses considerations regarding the therapeutic system design and the
      clinical application of task-oriented biofeedback therapy. This review should
      provide a framework to further broaden the application of task-oriented
      biofeedback therapy in neuromotor rehabilitation.

PMID- 16790062
TI  - Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes:
      a case based study.
AB  - BACKGROUND: Insulin is the recommend therapeutic agent of choice for the
      management of Cystic Fibrosis Related Diabetes (CFRD), despite only sub-optimal
      reductions in glycemic control and increased morbidity and mortality reported by
      centers using this agent. The newer insulin sensitizing agents demonstrated to
      have anti-inflammatory mechanisms may provide an alternative management option
      for CFRD. METHODS: A prospective case based therapeutic comparison between
      insulin, sulfonylurea, metformin and thiazolidinedione was observed over one
      decade with 20 CFRD patients diagnosed using American Diabetes Association
      guideline standards. Patients entering the study elected treatment based on risk
      and benefit information provided for treatment options. Patients receiving organ
      transplant or requiring combination diabetic medications were excluded from the
      study. RESULTS: No statistical advantage was achieved regarding overall glycemic
      control for oral agents over insulin. Additional outcome measures including
      changes in weight, liver function testing and FEV1 were not statistically
      significant. CONCLUSION: Insulin alone may not be the only therapeutic option in
      managing CFRD. Oral hypoglycemic agents were equally effective in treating CFRD
      and may provide an alternative class of agents for patients reluctant in using
      insulin.

PMID- 16790061
TI  - Trends in absolute socioeconomic inequalities in mortality in Sweden and New
      Zealand. A 20-year gender perspective.
AB  - BACKGROUND: Both trends in socioeconomic inequalities in mortality, and cross
      country comparisons, may give more information about the causes of health
      inequalities. We analysed trends in socioeconomic differentials by mortality from
      early 1980s to late 1990s, comparing Sweden with New Zealand. METHODS: The New
      Zealand Census Mortality Study (NZCMS) consisting of over 2 million individuals
      and the Swedish Survey of Living Conditions (ULF) comprising over 100, 000
      individuals were used for analyses. Education and household income were used as
      measures of socioeconomic position (SEP). The slope index of inequality (SII) was
      calculated to estimate absolute inequalities in mortality. Analyses were based on
      3-5 year follow-up and limited to individuals aged 25-77 years. Age standardised
      mortality rates were calculated using the European population standard. RESULTS:
      Absolute inequalities in mortality on average over the 1980s and 1990s for both
      men and women by education were similar in Sweden and New Zealand, but by income
      were greater in Sweden. Comparing trends in absolute inequalities over the 1980s
      and 1990s, men's absolute inequalities by education decreased by 66% in Sweden
      and by 17% in New Zealand (p for trend <0.01 in both countries). Women's absolute
      inequalities by education decreased by 19% in Sweden (p = 0.03) and by 8% in New
      Zealand (p = 0.53). Men's absolute inequalities by income decreased by 51% in
      Sweden (p for trend = 0.06), but increased by 16% in New Zealand (p = 0.13).
      Women's absolute inequalities by income increased in both countries: 12% in
      Sweden (p = 0.03) and 21% in New Zealand (p = 0.04). CONCLUSION: Trends in
      socioeconomic inequalities in mortality were clearly most favourable for men in
      Sweden. Trends also seemed to be more favourable for men than women in New
      Zealand. Assuming the trends in male inequalities in Sweden were not a
      statistical chance finding, it is not clear what the substantive reason(s) was
      for the pronounced decrease. Further gender comparisons are required.

PMID- 16790064
TI  - Antimicrobial and toxicological evaluation of the leaves of Baissea axillaries
      Hua used in the management of HIV/AIDS patients.
AB  - BACKGROUND: Persistent diarrhea is a common endemic disease with high incidence
      among the Africans including Nigerians. It also represents a frequent
      opportunistic disease in people living with HIV. Diarrhea represents one of the
      most distressful and persistent symptoms of HIV/AIDS, which may or may not be
      accompanied by an infection. The leaves decoction of Baissea axillaries Hua
      (Apocynaceae) is used by traditional herbalists in Edo state, Nigeria for the
      management of people living with HIV/AIDS. Determination of its antimicrobial
      activity and toxicological profile will provide supportive scientific evidence in
      favour of its continuous usage. METHOD: Chemical and chromatographic tests were
      employed in phytochemical investigations. Inhibitory activities of aqueous and
      ethanolic extracts against clinical strains of Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus aureus and Streptococcus faecalis were compared with
      Togamycin (Spectinomycin). Our report includes minimum inhibitory concentration
      (MIC) against the test organisms. Toxicological evaluation was determined by
      administering 250 mg/kg and 500 mg/kg of extracts on male Wister rats for 14 days
      with normal saline as control. The kidneys, liver, heart and testis tissues were
      examined. RESULTS: Phytochemical studies revealed the presence of alkaloids,
      tannins, and cyanogenetic glycosides. The extracts inhibited the growth of
      Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus to varying
      extents, but only the ethanolic extract inhibited growth in Streptococcus
      faecalis. The LD50 of the extract in mice was above 5000 mg/kg body weight when
      administered intraperitoneally. Toxicological evaluation showed mere ballooning
      degeneration of the liver at 250 mg/kg while at 500 mg/kg there was tissue
      necrosis. The low and high doses showed ill-defined leydig cells in the testis
      and no remarkable changes in the heart and kidneys. CONCLUSION: Extracts of
      Baissea axillaries have demonstrated antimicrobial activity against clinical
      strains of selected microorganisms. While there is toxicity at the dose of 500
      mg/kg, the therapy shows potential for application in the treatment of diarrhoea
      associated with AIDS/HIV. Further studies of Baissea axillaries on diarrhoea and
      toxicity are necessary to evaluate its mechanism of action and to fully establish
      its safety profile.

PMID- 16790063
TI  - PCR-based generation of shRNA libraries from cDNAs.
AB  - BACKGROUND: The use of small interfering RNAs (siRNAs) to silence target gene
      expression has greatly facilitated mammalian genetic analysis by generating loss
      of-function mutants. In recent years, high-throughput, genome-wide screening of
      siRNA libraries has emerged as a viable approach. Two different methods have been
      used to generate short hairpin RNA (shRNA) libraries; one is to use chemically
      synthesized oligonucleotides, and the other is to convert complementary DNAs
      (cDNAs) into shRNA cassettes enzymatically. The high cost of chemical synthesis
      and the low efficiency of the enzymatic approach have hampered the widespread use
      of screening with shRNA libraries. RESULTS: We report here an improved method for
      constructing genome-wide shRNA libraries enzymatically. The method includes steps
      of cDNA fragmentation and endonuclease MmeI digestion to generate 19-bp
      fragments, capping the 19-bp cDNA fragments with a hairpin oligonucleotide, and
      amplification of the hairpin structures by PCR. The PCR step converts hairpins
      into double-stranded DNAs that contain head-to-head cDNA fragments that can be
      cloned into a vector downstream of a Pol III promoter. CONCLUSION: This method
      can readily be used to generate shRNA libraries from a small amount of mRNA and
      thus can be used to create cell- or tissue-specific libraries.

PMID- 16790065
TI  - Transient integral boundary layer method to calculate the translesional pressure
      drop and the fractional flow reserve in myocardial bridges.
AB  - BACKGROUND: The pressure drop-flow relations in myocardial bridges and the
      assessment of vascular heart disease via fractional flow reserve (FFR) have
      motivated many researchers the last decades. The aim of this study is to simulate
      several clinical conditions present in myocardial bridges to determine the flow
      reserve and consequently the clinical relevance of the disease. From a fluid
      mechanical point of view the pathophysiological situation in myocardial bridges
      involves fluid flow in a time dependent flow geometry, caused by contracting
      cardiac muscles overlying an intramural segment of the coronary artery. These
      flows mostly involve flow separation and secondary motions, which are difficult
      to calculate and analyse. METHODS: Because a three dimensional simulation of the
      haemodynamic conditions in myocardial bridges in a network of coronary arteries
      is time-consuming, we present a boundary layer model for the calculation of the
      pressure drop and flow separation. The approach is based on the assumption that
      the flow can be sufficiently well described by the interaction of an inviscid
      core and a viscous boundary layer. Under the assumption that the idealised flow
      through a constriction is given by near-equilibrium velocity profiles of the
      Falkner-Skan-Cooke (FSC) family, the evolution of the boundary layer is obtained
      by the simultaneous solution of the Falkner-Skan equation and the transient von
      Karman integral momentum equation. RESULTS: The model was used to investigate the
      relative importance of several physical parameters present in myocardial bridges.
      Results have been obtained for steady and unsteady flow through vessels with 0 -
      85% diameter stenosis. We compare two clinical relevant cases of a myocardial
      bridge in the middle segment of the left anterior descending coronary artery
      (LAD). The pressure derived FFR of fixed and dynamic lesions has shown that the
      flow is less affected in the dynamic case, because the distal pressure partially
      recovers during re-opening of the vessel in diastole. We have further calculated
      the wall shear stress (WSS) distributions in addition to the location and length
      of the flow reversal zones in dependence on the severity of the disease.
      CONCLUSION: The described boundary layer method can be used to simulate
      frictional forces and wall shear stresses in the entrance region of vessels.
      Earlier models are supplemented by the viscous effects in a quasi three
      dimensional vessel geometry with a prescribed wall motion. The results indicate
      that the translesional pressure drop and the mean FFR compares favourably to
      clinical findings in the literature. We have further shown that the mean FFR
      under the assumption of Hagen-Poiseuille flow is overestimated in developing flow
      conditions.

PMID- 16790066
TI  - Gitksan medicinal plants--cultural choice and efficacy.
AB  - BACKGROUND: The use of plants for healing by any cultural group is integrally
      related to local concepts of the nature of disease, the nature of plants, and the
      world view of the culture. The physical and chemical properties of the plants
      themselves also bear on their selection by people for medicines, as does the
      array of plants available for people to choose from. I examine use of medicinal
      plants from a "biobehavioral" perspective to illuminate cultural selection of
      plants used for medicine by the Gitksan of northwestern British Columbia, Canada.
      METHODS: Consultant consensus, "intercultural consensus", independent use of the
      same plants by other cultural groups, and phytochemistry and bioassay results
      from the literature, were employed in analysis of probable empirical efficacy of
      plant uses. RESULTS: 70% of 37 Gitksan medicinal plants were used similarly by
      other cultures where direct diffusion is not known to have occurred; eleven
      plants, including the eight most frequently mentioned medicinal plants, also show
      active phytochemicals or bioassays indicating probable physiologically based
      therapeutic effects. CONCLUSION: Analysis of intercultural consensus revealed
      that the majority of cultures in the British Columbia region within the plant
      ranges use the same plants, or closely related species, in similar ways. The
      rigor of this analysis is effected by the lack of consistent data on all taxa of
      interest for all cultures within the region.

PMID- 16790067
TI  - Robot-assisted reaching exercise promotes arm movement recovery in chronic
      hemiparetic stroke: a randomized controlled pilot study.
AB  - BACKGROUND AND PURPOSE: Providing active assistance to complete desired arm
      movements is a common technique in upper extremity rehabilitation after stroke.
      Such active assistance may improve recovery by affecting somatosensory input,
      motor planning, spasticity or soft tissue properties, but it is labor intensive
      and has not been validated in controlled trials. The purpose of this study was to
      investigate the effects of robotically administered active-assistive exercise and
      compare those with free reaching voluntary exercise in improving arm movement
      ability after chronic stroke. METHODS: Nineteen individuals at least one year
      post-stroke were randomized into one of two groups. One group performed 24
      sessions of active-assistive reaching exercise with a simple robotic device,
      while a second group performed a task-matched amount of unassisted reaching. The
      main outcome measures were range and speed of supported arm movement, range,
      straightness and smoothness of unsupported reaching, and the Rancho Los Amigos
      Functional Test of Upper Extremity Function. RESULTS AND DISCUSSION: There were
      significant improvements with training for range of motion and velocity of
      supported reaching, straightness of unsupported reaching, and functional movement
      ability. These improvements were not significantly different between the two
      training groups. The group that performed unassisted reaching exercise improved
      the smoothness of their reaching movements more than the robot-assisted group.
      CONCLUSION: Improvements with both forms of exercise confirmed that repeated,
      task-related voluntary activation of the damaged motor system is a key stimulus
      to motor recovery following chronic stroke. Robotically assisting in reaching
      successfully improved arm movement ability, although it did not provide any
      detectable, additional value beyond the movement practice that occurred
      concurrently with it. The inability to detect any additional value of robot
      assisted reaching may have been due to this pilot study's limited sample size,
      the specific diagnoses of the participants, or the inclusion of only individuals
      with chronic stroke.

PMID- 16790068
TI  - Endothelial progenitor cells display clonal restriction in multiple myeloma.
AB  - BACKGROUND: In multiple myeloma (MM), increased neoangiogenesis contributes to
      tumor growth and disease progression. Increased levels of endothelial progenitor
      cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with
      disease activity and response to treatment. In order to understand the mechanisms
      responsible for increased EPC levels and neoangiogenic function in MM, we
      investigated whether these cells were clonal by determining X-chromosome
      inactivation (XCI) patterns in female patients by a human androgen receptor assay
      (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence
      of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which
      indicates clonality in B cells; thus, its presence in EPCs would indicate a close
      genetic link between tumor cells in MM and endothelial cells that provide tumor
      neovascularization. METHODS: A total of twenty-three consecutive patients who had
      not received chemotherapy were studied. Screening in 18 patients found that 11
      displayed allelic AR in peripheral blood mononuclear cells, and these patients
      were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2
      patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients,
      EPCs were studied for IGH gene rearrangement using PCR with family-specific
      primers for IGH variable genes (VH). RESULTS: In 11 patients, analysis of EPCs by
      HUMARA revealed significant skewing (> or = 77% expression of a single allele) in
      64% (n = 7). In 4 of these patients, XCI skewing was extreme (> or = 90%
      expression of a single allele). In contrast, XCI in hair root cells was random.
      Furthermore, PCR amplification with VH primers resulted in amplification of the
      same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no
      IGH rearrangement was found in EPCs from healthy controls. In addition, in
      patients with XCI skewing in EPCs, advanced age was associated with poorer
      clinical status, unlike patients whose EPCs had random XCI. CONCLUSION: Our
      results suggest that EPCs in at least a substantial subpopulation of MM patients
      are related to the neoplastic clone and that this is an important mechanism for
      upregulation of tumor neovascularization in MM.

PMID- 16790069
TI  - Prognosis of acute low back pain: design of a prospective inception cohort study.
AB  - BACKGROUND: Clinical guidelines generally portray acute low back pain as a benign
      and self-limiting condition. However, evidence about the clinical course of acute
      low back pain is contradictory and the risk of subsequently developing chronic
      low back pain remains uncertain. There are few high quality prognosis studies and
      none that have measured pain, disability and return to work over a 12 month
      period. This study aims to provide the first estimates of the one year prognosis
      of acute low back pain (pain of less than 2 weeks duration) in patients
      consulting primary care practitioners. A secondary aim is to identify factors
      that are associated with the prognosis of low back pain. METHODS/DESIGN: The
      study is a prospective inception cohort study. Consecutive patients consulting
      general medical practitioners, physiotherapists and chiropractors in the Sydney
      metropolitan region will complete a baseline questionnaire regarding their back
      pain. Subsequently these patients will be followed up by telephone 6 weeks, 3
      months and 12 months after the initial consultation. Patients will be considered
      to have recovered from the episode of back pain if they have no pain and no
      limitation of activity, and have returned to pre-injury work status. Life tables
      will be generated to determine the one year prognosis of acute low back pain.
      Prognostic factors will be assessed using Cox regression. DISCUSSION: This study
      will provide the first estimates of the one year prognosis of acute low back pain
      in a representative sample of primary care patients.

PMID- 16790070
TI  - Effectiveness of a Chinese herbal medicine preparation in the treatment of cough
      in uncomplicated upper respiratory tract infection: a randomised double-blinded
      placebo-control trial.
AB  - BACKGROUND: Rigorous scientific and well-designed clinical trials to evaluate the
      effect of traditional Chinese medicine (TCM) is lacking. We, therefore, designed
      this study to evaluate the effectiveness of a commonly used TCM preparation in
      treating acute cough of uncomplicated URTI in adults and to search for a safe,
      effective and affordable alternative treatment for this common condition.
      METHODS: A randomised, double-blinded, placebo-control study comparing this TCM
      preparation with a placebo was conducted in 82 patients who attended the Family
      Medicine Training Centre, Prince of Wales Hospital, Hong Kong between November
      and December, 2003. The TCM herbal preparation includes nine commonly used TCM
      herbs for cough such as chuanbei, fangfeng, jiegeng, gancao and baibu (see Table
      1). The treatment lasted for 5 days and patients were followed-up for another 6
      days. Patients were asked to fill in a cough score and validated Leicester cough
      questionnaire (LCQ). RESULTS: 62 patients (75.6%) had completed the trial and no
      adverse effects were reported. Both intervened and control groups had improved in
      cough score and LCQ in the follow-up period, despite no overall statistical
      significance was observed in the differences of scores between the two groups.
      Women taking TCM had significantly fewer problems with sputum production (p =
      0.03) and older subjects (>35 years of age) reported a significant improvement in
      hoarseness (p = 0.05) when compared to those using placebo. CONCLUSION: TCM was
      well-tolerated and received among the Hong Kong Chinese population. This TCM
      preparation appeared to have some benefits in the treatment of cough. Future
      research on TCM should concentrate more on commonly encountered conditions such
      as UTRI and cough. Our experience on the sensitivity of assessment tools used in
      detecting subtle differences in an otherwise self-limiting illness and clinical
      trial methodology when applying the underlying theory of how TCM works in disease
      management was invaluable.

PMID- 16790071
TI  - Hormonal priming, induction of ovulation and in-vitro fertilization of the
      endangered Wyoming toad (Bufo baxteri).
AB  - The endangered Wyoming toad (Bufo baxteri) is the subject of an extensive captive
      breeding and reintroduction program. Wyoming toads in captivity rarely ovulate
      spontaneously and hormonal induction is used to ovulate females or to stimulate
      spermiation in males. With hormonal induction, ovulation is unreliable and egg
      numbers are low. The sequential administration of anovulatory doses of hormones
      (priming) has increased egg numbers and quality in both anurans and fish.
      Consequently, we tested the efficacy of a combination of human Chorionic
      Gonadotrophin (hCG) and Luteinizing Hormone Releasing Hormone analogue (LHRHa)
      administered as one dose, or two or three sequential doses to Bufo baxteri on egg
      numbers, fertilization and early embryo development. Spawning toads deposited
      eggs into Simplified Amphibian Ringers (SAR) solution to enable controlled in
      vitro fertilization (IVF) with sperm from hormonally induced male toads. Unprimed
      females receiving a single mixed normally ovulatory dose of 500 IU hCG plus 4
      micrograms of LHRHa produced no eggs. Whereas females primed with this dose and
      an anovulatory dose (100 IU hCG and 0.8 micrograms of LHRHa) of the same
      hormones, or primed only with an anovulatory dose, spawned after then receiving
      an ovulatory dose. Higher total egg numbers were produced with two primings than
      with one priming. Moreover, two primings produced significantly more eggs from
      each individual female than one priming. The cleavage rate of eggs was not found
      to differ between one or two primings. Nevertheless, embryo development with eggs
      from two primings gave a significantly greater percentage neurulation and swim-up
      than those from one priming. Of the male toads receiving a single dose of 300 IU
      hCG, 80% produced spermic urine with the greatest sperm concentration 7 hours
      post-administration (PA). However, peak sperm motility (95%) was achieved at 5
      hours PA and remained relatively constant until declining 20 hours PA. In
      conclusion, Bufo baxteri egg numbers and quality benefited from sequential
      priming with LHRHa and hCG whereas spermic urine for IVF was produced from males
      with a single dose of hCG. The power of assisted reproduction technology in the
      conservation of endangered amphibians is shown by the release of nearly 2000
      tadpoles produced by IVF during this study.

PMID- 16790072
TI  - Sorting of cells of the same size, shape, and cell cycle stage for a single cell
      level assay without staining.
AB  - BACKGROUND: Single-cell level studies are being used increasingly to measure cell
      properties not directly observable in a cell population. High-performance data
      acquisition systems for such studies have, by necessity, developed in synchrony.
      However, improvements in sample purification techniques are also required to
      reveal new phenomena. Here we assessed a cell sorter as a sample-pretreatment
      tool for a single-cell level assay. A cell sorter is routinely used for selecting
      one type of cells from a heterogeneous mixture of cells using specific
      fluorescence labels. In this case, we wanted to select cells of exactly the same
      size, shape, and cell-cycle stage from a population, without using a specific
      fluorescence label. RESULTS: We used four light scatter parameters: the peak
      height and area of the forward scatter (FSheight and FSarea) and side scatter
      (SSheight and SSarea). The rat pheochromocytoma PC12 cell line, a neuronal cell
      line, was used for all experiments. The living cells concentrated in the high
      FSarea and middle SSheight/SSarea fractions. Single cells without cell clumps
      were concentrated in the low SS and middle FS fractions, and in the higher
      FSheight/FSarea and SSheight/SSarea fractions. The cell populations from these
      viable, single-cell-rich fractions were divided into twelve subfractions based on
      their FSarea-SSarea profiles, for more detailed analysis. We found that SSarea
      was proportional to the cell volume and the FSarea correlated with cell roundness
      and elongation, as well as with the level of DNA in the cell. To test the method
      and to characterize the basic properties of the isolated single cells, sorted
      cells were cultured in separate wells. The cells in all subfractions survived,
      proliferated and differentiated normally, suggesting that there was no serious
      damage. The smallest, roundest, and smoothest cells had the highest viability.
      There was no correlation between proliferation and differentiation. NGF increases
      cell viability but decreases the proliferative ability of the PC12 cells.
      CONCLUSION: We demonstrated a pretreatment method to collect well-characterized,
      viable, single cells without using fluorescent labels and without significant
      damage to the cells. This method is quantitative, rapid, single-step, and yields
      cells of high purity, making it applicable for a variety of single-cell level
      analyses.

PMID- 16790073
TI  - Does a preceding hand wash and drying time after surgical hand disinfection
      influence the efficacy of a propanol-based hand rub?
AB  - BACKGROUND: Recently, a propanol-based hand rub has been described to exceed the
      efficacy requirements of the European standard EN 12791 in only 1.5 min
      significantly. But the effect of a 1 min preceding hand wash and the effect of
      one additional minute for evaporation of the alcohol after its application on the
      efficacy after a 1.5 min application time has never been studied. METHODS: We
      have investigated a propanol-based hand rub (Sterillium, based on 45% propan-2
      ol, 30% propan-1-ol and 0.2% mecetronium etilsulfate) in three variations: with
      (A) and without (B) a 1 min hand wash before the disinfection of 1.5 min with
      immediate sampling after the disinfection; and (C) without a hand wash before the
      disinfection but with sampling 1 min after the disinfection. The efficacy of the
      three variations was compared to the reference treatment of EN 12791. All
      experiments were performed in a Latin-square design with 20 volunteers. Pre- and
      post-values (immediate and after 3 hr) were obtained according to EN 12791.
      RESULTS: The 3 min reference disinfection reduced resident hand bacteria on
      average by 1.8 log10 steps (immediate effect) and 1.4 log10-steps (sustained
      effect) respectively. Method A was equally effective as the reference (immediate
      efficacy: 1.5 log10-steps; sustained efficacy: 1.6 log10-steps). Method B seemed
      to be more effective (immediate efficacy: 2.3 log10-steps; sustained efficacy:
      1.7 log10-steps). Method C revealed the best efficacy (immediate efficacy: 2.3
      log10-steps; sustained efficacy: 2.0 log10-steps). A comparison of all three
      treatment variations and the reference treatment revealed a significant
      difference for the immediate efficacy (p = 0.026; Friedman test), but not for the
      sustained efficacy (p = 0.430). A post-hoc-test for the immediate efficacy
      indicated a significant difference between methods A and C (p < 0.05; Wilcoxon
      Wilcox test). Hence, none of the treatment variations was significantly less
      effective than the reference treatment. CONCLUSION: An application of the
      propanol-based hand rub for 1.5 min after 1 min hand wash fulfills the efficacy
      requirements of EN 12791. The efficacy can be improved to some extent by omitting
      the preceding hand wash and by awaiting the evaporation of the alcohol which is
      clinical practice anyway. The preceding hand wash has the most negative effect on
      the immediate effect. Based on our data hands should not be routinely washed
      before the disinfection period unless there is a good reason for it such as
      visible soiling.

PMID- 16790074
TI  - Alteration of serotonin transporter density and activity in fibromyalgia.
AB  - The aim of the study was to evaluate the kinetic parameters of a specific
      serotonin transporter (SERT) and serotonin uptake in a mentally healthy subset of
      patients with fibromyalgia. Platelets were obtained from 40 patients and 38
      healthy controls. SERT expression and functionality were evaluated through the
      measurement of [3H]paroxetine binding and the [3H]serotonin uptake itself. The
      values of maximal membrane binding capacity (Bmax) were statistically lower in
      the patients than in the healthy volunteers, whereas the dissociation constant
      (Kd) did not show any statistically significant variations. Moreover, a decrease
      in the maximal uptake rate of SERT (Vmax) was demonstrated in the platelets of
      patients, whereas the Michaelis constant (Km) did not show any statistically
      significant variations. Symptom severity score (tiredness, tender points index
      and Fibromyalgia Impact Questionnaire) were negatively correlated with Bmax and
      with Vmax, and positively correlated with Km. A change in SERT seems to occur in
      fibromyalgic patients, and it seems to be related to the severity of fibromyalgic
      symptoms.

PMID- 16790075
TI  - Keratin 6 is not essential for mammary gland development.
AB  - INTRODUCTION: Keratin 6 (K6) has previously been identified as a marker of early
      mammary gland development and has also been proposed to be a marker of mammary
      gland progenitor cells. However, the function of K6 in the mammary gland was not
      known, so we examined the expression pattern of the protein during both embryonic
      and postnatal mammary development, as well as the mammary gland phenotype of mice
      that were null for both K6a and K6b isoforms. METHOD: Immunostaining was
      performed to determine the expression pattern of K6a throughout mammary gland
      development, from the embryonic mammary bud to lactation. Double
      immunofluorescence was used to co-localize K6 with known markers of mammary gland
      development. Wild-type and K6ab-null mammary tissues were transplanted into the
      cleared fat pads of nude mice and the outgrowths were analyzed for morphology by
      whole-mount staining and for markers of mammary epithelium by immunostaining.
      Finally, progesterone receptor (PR) and bromodeoxyuridine co-localization was
      quantified by double immunofluorescence in wild-type and K6ab-null mammary
      outgrowths. RESULTS: Here we report that K6 is expressed earlier than described
      previously, by embryonic day 16.5. K6a is the predominant isoform expressed in
      the mammary gland, localized in the body cells and luminal epithelial cells but
      not in the cap cells or myoepithelial cells. Co-localization studies showed that
      most K6a-positive cells express steroid receptors but do not proliferate. When
      both the K6a and K6b genes are deleted, mammary gland development appears normal,
      with similar expression of most molecular markers examined in both the pubertal
      gland and the mature gland. Loss of K6a and K6b, however, leads to an increase in
      the number of steroid-receptor-positive cells, and increased co-localization of
      steroid receptor expression and proliferation was observed. CONCLUSION: Although
      K6a was not essential for mammary gland development, loss of both K6a and K6b
      resulted in an increase in PR-positive mammary epithelial cells and decreased
      proliferation after exposure to steroid hormones. There was also increased co
      localization of PR and bromodeoxyuridine, suggesting alterations in patterning
      events important for normal lobuloalveolar development.

PMID- 16790076
TI  - Evaluation of Ki-67 proliferation and apoptotic index before, during and after
      neoadjuvant chemotherapy for primary breast cancer.
AB  - INTRODUCTION: Biological markers that reliably predict clinical or pathological
      response to primary systemic therapy early during a course of chemotherapy may
      have considerable clinical potential. This study evaluated changes in Ki-67
      labeling index and apoptotic index (AI) before, during, and after neoadjuvant
      anthracycline chemotherapy. METHODS: Twenty-seven patients receiving neoadjuvant
      FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for operable
      breast cancer underwent repeat core biopsy after 21 days of treatment. Tissue
      from pre-treatment biopsy, day 21 and surgery was analysed for Ki-67 index and
      AI. RESULTS: The objective clinical response rate was 56%. Eight patients (31%)
      achieved a pathological response by histological criteria; two patients had a
      near-complete pathological response. A reduction in Ki-67 index was observed in
      68% of patients at day 21 and 72% at surgery; Ki-67 index increased between day
      21 and surgery in 54%. AI decreased in 50% of tumours by day 21, increased in 45%
      and was unchanged in one patient; 56% demonstrated rebound increases in AI by the
      time of surgery. Neither pre-treatment nor post-chemotherapy median Ki-67 index
      nor median AI at all three time points or relative changes at day 21 and surgery
      differed significantly between clinical or pathological responders and non
      responders. Clinical responders had lower median Ki-67 indices at day 21 (11.4%
      versus 27.0%, p = 0.02) and significantly greater percentage reductions in Ki-67
      at day 21 than did non-responders (-50.6% versus -5.3%, p = 0.04). The median day
      21 Ki-67 was higher in pathological responders (30.3% versus 14.1%, p = 0.046). A
      trend toward increased AI at day 21 in pathological responders was observed (5.30
      versus 1.68, p = 0.12). Increased day-21 AI was a statistically significant
      predictor of pathological response (p = 0.049). A strong trend for predicting
      pathological response was seen with higher Ki-67 indices at day 21 and AI at
      surgery (p = 0.06 and 0.06, respectively). CONCLUSION: The clinical utility of
      early changes in biological marker expression during chemotherapy remains
      unclear. Until further prospectively validated evidence confirming the
      reliability of predictive markers is available, clinical decision-making should
      not be based upon individual biological tumour marker profiles.

PMID- 16790077
TI  - The effect of the stromal component of breast tumours on prediction of clinical
      outcome using gene expression microarray analysis.
AB  - INTRODUCTION: The aim of this study was to examine the effect of the cellular
      composition of biopsies on the error rates of multigene predictors of response of
      breast tumours to neoadjuvant adriamycin and cyclophosphamide (AC) chemotherapy.
      MATERIALS AND METHODS: Core biopsies were taken from primary breast tumours of 43
      patients prior to AC, and subsequent clinical response was recorded. Post
      chemotherapy (day 21) samples were available for 16 of these samples. Frozen
      sections of each core were used to estimate the proportion of invasive cancer and
      other tissue components at three levels. Transcriptional profiling was performed
      using a cDNA array containing 4,600 elements. RESULTS: Twenty-three (53%)
      patients demonstrated a 'good' and 20 (47%) a 'poor' clinical response. The
      percentage invasive tumour in core biopsies collected from these patients varied
      markedly. Despite this, agglomerative clustering of sample expression profiles
      showed that almost all biopsies from the same tumour aggregated as nearest
      neighbours. SAM (significance analysis of microarrays) regression analysis
      identified 144 genes which distinguished high- and low-percentage invasive tumour
      biopsies at a false discovery rate of not more than 5%. The misclassification
      error of prediction of clinical response using microarray data from pre-treatment
      biopsies (on leave-one-out cross-validation) was 28%. When prediction was
      performed on subsets of samples which were more homogeneous in their proportions
      of malignant and stromal cells, the misclassification error was considerably
      lower (8%-13%, p < 0.05 on permutation). CONCLUSION: The non-tumour content of
      breast cancer samples has a significant effect on gene expression profiles.
      Consideration of this factor improves accuracy of response prediction by
      expression array profiling. Future gene expression array prediction studies
      should be planned taking this into account.

PMID- 16790078
TI  - Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients
      with and without subcutaneous oedema: a pilot study.
AB  - INTRODUCTION: Intensive care unit (ICU) patients often suffer from subcutaneous
      oedema, due to administration of large fluid volumes and the underlying
      pathophysiological condition. It is unknown whether the presence of subcutaneous
      oedema impairs the absorption of dalteparin, a low molecular weight heparin, when
      it is given by subcutaneous administration for venous thromboembolism
      prophylaxis. The objective of this study is to compare the anti-Xa activity of
      dalteparin after subcutaneous administration in ICU patients with and without
      subcutaneous oedema. METHODS: This non-randomized open parallel group follow-up
      pilot study was conducted in two mixed medical-surgical intensive care units at
      two teaching hospitals. Seven ICU patients with subcutaneous oedema (index group)
      and seven ICU patients without subcutaneous oedema (reference group) were
      studied. Anti-Xa activity was determined at 0, 3, 4, 6, 8, 12 and 24 hours after
      subcutaneous administration of 2,500 IU dalteparin. Plasma concentrations of
      factor anti-Xa activity were measured using a chromogenic factor Xa inhibition
      assay. RESULTS: The characteristics of the index group were: age, 58 years;
      male/female ratio, 5/2; body mass index at admission, 23.4 kg/m2 (at study day,
      30.6 kg/m2). The characteristics of the reference group were: age, 49 years;
      male/female ratio, 6/1; body mass index at admission, 24.8 kg/m2 (at study day,
      25.0 kg/m2). In the index group, creatinine clearance was lower compared to the
      reference group (71 versus 131 ml/minute, p = 0.003). Sequential organ failure
      assessment score did not differ between index and reference groups (4 versus 5).
      Mean arterial pressure was comparable between index and reference groups (91
      versus 95 mmHg) and within the normal range. The mean Cmax value was not
      different between ICU patients with and without subcutaneous oedema (0.15 +/-
      0.02 versus 0.14 +/- 0.02 IU/ml, p = 0.34). In the index group, the mean AUC(0-24
      h) value was slightly higher compared with the reference group (1.50 +/- 0.31
      versus 1.15 +/- 0.25 h.IU/ml, p = 0.31). This difference was not significant.
      CONCLUSION: In this pilot study, there was no clinically relevant difference in
      anti-Xa activity after subcutaneous administration of 2,500 IU dalteparin for
      venous thromboembolism prophylaxis between ICU patients with and without
      subcutaneous oedema. Critically ill patients seem to have lower anti-Xa activity
      levels than healthy volunteers.

PMID- 16790079
TI  - Human cell type diversity, evolution, development, and classification with
      special reference to cells derived from the neural crest.
AB  - Metazoans are composed of a finite number of recognisable cell types. Similar to
      the relationship between species and ecosystems, knowledge of cell type diversity
      contributes to studies of complexity and evolution. However, as with other units
      of evolution, the cell type often resists definition. This review proposes
      guidelines for characterising cell types and discusses cell homology and the
      various developmental pathways by which cell types arise, including germ layers,
      blastemata (secondary development/neurulation), stem cells, and
      transdifferentiation. An updated list of cell types is presented for a familiar,
      albeit overlooked model taxon, adult Homo sapiens, with 411 cell types, including
      145 types of neurons, recognised. Two methods for organising these cell types are
      explored. One is the artificial classification technique, clustering cells using
      commonly accepted criteria of similarity. The second approach, an empirical
      method modeled after cladistics, resolves the classification in terms of shared
      features rather than overall similarity. While the results of each scheme differ,
      both methods address important questions. The artificial classification provides
      compelling (and independent) support for the neural crest as the fourth germ
      layer, while the cladistic approach permits the evaluation of cell type
      evolution. Using the cladistic approach we observe a correlation between the
      developmental and evolutionary origin of a cell, suggesting that this method is
      useful for predicting which cell types share common (multipotential) progenitors.
      Whereas the current effort is restricted by the availability of phenotypic
      details for most cell types, the present study demonstrates that a comprehensive
      cladistic classification is practical, attainable, and warranted. The use of cell
      types and cell type comparative classification schemes has the potential to offer
      new and alternative models for therapeutic evaluation.

PMID- 16790080
TI  - Differential motivational responses to food and pleasurable cues in anorexia and
      bulimia nervosa: a startle reflex paradigm.
AB  - BACKGROUND: Abnormal perceptions of food and shape underpin the cognitive
      behavioural model of eating disorders (EDs). The aim of this study was to
      investigate motivational processing of disorder-specific and standard emotional
      cues in anorexia (AN) and bulimia nervosa (BN) using startle eyeblink modulation
      (SEM). SEM was used because it is sensitive to motivational states of approach
      (appetitive response) and withdrawal (aversive response), which are independent
      of conscious intentional control. METHOD: Acoustically elicited SEM and
      subjective anxiety ratings were measured in 30 female patients with an ED (n=15
      AN, n=15 BN) and 30 female control subjects while they viewed ED-relevant stimuli
      (food, female bodies) and standardized emotional pictures. RESULTS: BN subjects
      showed an appetitive response (startle inhibition) to food relative to neutral
      cues that differed significantly from AN subjects. By contrast, self-reports
      indicated significantly increased anxiety related to food cues across both ED
      groups. To female body picture (relative to neutral) cues, no significant between
      group differences were found for SEM. ED subjects unexpectedly showed an aversive
      response (startle potentiation) to positive cues, in contrast to controls, who
      showed the established startle attenuation. CONCLUSIONS: These preliminary
      results suggest that BN patients demonstrated an exaggerated appetitive response
      to food but not to standardized positive cues, whereas SEM in AN patients points
      to a generalized failure to activate the appetitive motivational system.
      Differences in motivational salience to food cues are in line with distinctions
      between AN and BN in eating behaviour and food consumption and support
      differential treatment requirements.

PMID- 16790081
TI  - Does marital status and marital status change predict physical health in older
      adults?
AB  - BACKGROUND: Evidence for the effects of marital status and marital status change
      on physical health is equivocal. METHOD: Structural equation models examined
      whether marital status predicted physical health. Six groups were examined
      simultaneously: married (M); widowed (W); divorced (D); never married (NM); newly
      widowed (NW); and newly divorced (ND). There were four annual measures (T1-T4).
      Both NW and ND were married at T1, but had lost their partners by T2. Four
      physical health variables were examined: Problems, Limitations, Service use, and
      Self-rated health (SRH). Age and gender were included. RESULTS: Previous health
      predicted future for all measures and for all groups. However, the specific
      strengths and time-courses varied between marital status groups and between
      health measures. The most marked patterns were associated with marital status
      change. Service use was influenced most strongly by NW, whilst Limitations was
      influenced by ND. Problems distinguished NW and ND from stable marital status
      groups but also from each other. SRH was influenced by W and not by recent
      marital status change. The effects of age and gender were modest and restricted
      to specific health variables and specific marital statuses. CONCLUSIONS: The
      results demonstrate that marital status and marital status change, in particular,
      influence health longitudinally. The impact of a change to divorced or to widowed
      status is not the same. No two health variables responded in the same way,
      suggesting that marital status has a differential effect on health.

PMID- 16790082
TI  - Novel genes implicated in embryonal, alveolar, and pleomorphic rhabdomyosarcoma:
      a cytogenetic and molecular analysis of primary tumors.
AB  - Rhabdomyosarcoma, the most common pediatric soft tissue sarcoma, likely results
      from deregulation of the skeletal myogenesis program. Although associations
      between PAX3, PAX7, FOXO1A, and RMS tumorigenesis are well recognized, the entire
      spectrum of genetic factors underlying RMS development and progression is
      unclear. Using a combined approach of spectral karyotyping, array-based
      comparative genomic hybridization (CGH), and expression analysis, we examined 10
      primary RMS tumors, including embryonal, alveolar, and the rare adult pleomorphic
      variant, to explore the involvement of different genes and genetic pathways in
      RMS tumorigenesis. A complete karyotype established for each tumor revealed a
      high aneuploidy level, mostly tetraploidy, with double minutes and additional
      structural aberrations. Quantitative expression analysis detected the
      overexpression of the AURKA gene in all tumors tested, suggesting a role for this
      mitotic regulator in the aneuploidy and chromosomal instability observed in RMS.
      Array-based CGH analysis in primary RMS tumors detected copy number changes of
      genes involved in multiple genetic pathways, including transcription factors such
      as MYC-related gene from lung cancer and the cytoskeleton and cell adhesion
      encoding genes laminin gamma-2 and p21-activated kinase-1. Our data suggest the
      involvement of genes encoding cell adhesion, cytoskeletal signaling, and
      transcriptional and cell cycle components in RMS tumorigenesis.

PMID- 16790083
TI  - HGF/SF increases tumor blood volume: a novel tool for the in vivo functional
      molecular imaging of Met.
AB  - Molecular functional and metabolic imaging allows visualization of disease
      causing processes in living organisms. Here we present a new approach for the
      functional molecular imaging (FMI) of endogenous tyrosine kinase receptor
      activity using Met and its ligand, hepatocyte growth factor/scatter factor
      (HGF/SF), as a model. HGF/SF and Met play significant roles in the biology and
      pathogenesis of a wide variety of cancers and, therefore, may serve as potential
      targets for cancer prognosis and therapy. We have previously shown that Met
      activation by HGF/SF increases oxygen consumption in vitro and results in
      substantial alteration of blood oxygenation levels in vivo, as measured by blood
      oxygenation level-dependent magnetic resonance imaging. Using contrast medium
      (CM) ultrasound imaging, we demonstrate here that HGF/SF induces an increase in
      tumor blood volume. This increase is evident in small vessels, including vessels
      that were not detected before HGF/SF treatment. The specificity of the effect was
      validated by its inhibition using anti-HGF/SF antibodies. This change in tumor
      hemodynamics, induced by HGF/SF and measured by CM ultrasound, is further used as
      a tool for Met FMI in tumors. This novel noninvasive molecular imaging technique
      may be applied for the in vivo diagnosis, prognosis, and therapy of Met
      expressing tumors.

PMID- 16790085
TI  - Angiopoietin-4 inhibits angiogenesis and reduces interstitial fluid pressure.
AB  - Angiopoietins (Ang) are involved in the remodeling, maturation, and stabilization
      of the vascular network. Ang-4 was discovered more recently; thus, its effect on
      angiogenesis and its interplay with other angiogenic factors have not been
      equivocally established. The role of Ang-4 in angiogenesis was tested in Matrigel
      chambers implanted into the subcutaneous space of nude mice. Ang-4 inhibited the
      angiogenic response of basic fibroblast growth factor (bFGF), vascular
      endothelial growth factor (VEGF), and GLC19 tumor cells. In Matrigel chambers
      with Ang-4-transfected cells, the mean response was significantly lower than that
      of mock cells. Subcutaneous tumor interstitial fluid pressure (IFP) was
      significantly lower in Ang-4-transfected GLC19 tumors than in mock-transfected
      tumors. IFP reduction in Ang-4-transfected tumors was comparable to the reduction
      seen after bevacizumab treatment. In vitro, we examined the effect of recombinant
      Ang-4 on endothelial cell migration in Boyden chambers. Human umbilical vein
      endothelial cell (HUVEC) migration induced by bFGF and VEGF was inhibited by Ang
      4 to control levels. In conclusion, we show that rhAng-4, as well as transfection
      with Ang-4, inhibits angiogenesis induced by GLC19 tumor cells and that Ang-4
      expression reduces elevated tumor IFP. In addition, we demonstrate that rhAng-4
      inhibits HUVEC migration and growth factor-induced angiogenesis.

PMID- 16790084
TI  - In vivo direct molecular imaging of early tumorigenesis and malignant progression
      induced by transgenic expression of GFP-Met.
AB  - The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor/scatter
      factor (HGF/SF), play an important role in normal developmental processes, as
      well as in tumorigenicity and metastasis. We constructed a green fluorescent
      protein (GFP) Met chimeric molecule that functions similarly to the wild-type Met
      receptor and generated GFP-Met transgenic mice. These mice ubiquitously expressed
      GFP-Met in specific epithelial and endothelial cells and displayed enhanced GFP
      Met fluorescence in sebaceous glands. Thirty-two percent of males spontaneously
      developed adenomas, adenocarcinomas, and angiosarcomas in their lower abdominal
      sebaceous glands. Approximately 70% of adenocarcinoma tumors metastasized to the
      kidneys, lungs, or liver. Quantitative subcellular-resolution intravital imaging
      revealed very high levels of GFP-Met in tumor lesions and in single isolated
      cells surrounding them, relative to normal sebaceous glands. These single cells
      preceded the formation of local and distal metastases. Higher GFP-Met levels
      correlated with earlier tumor onset and aggressiveness, further demonstrating the
      role of Met-HGF/SF signaling in cellular transformation and acquisition of
      invasive and metastatic phenotypes. Our novel mouse model and high-resolution
      intravital molecular imaging create a powerful tool that enables direct real-time
      molecular imaging of receptor expression and localization during primary events
      of tumorigenicity and metastasis at single-cell resolution.

PMID- 16790086
TI  - Gene expression profile related to the progression of preneoplastic nodules
      toward hepatocellular carcinoma in rats.
AB  - In this study, we investigated the time course gene expression profile of
      preneoplastic nodules and hepatocellular carcinomas (HCC) to define the genes
      implicated in cancer progression in a resistant hepatocyte model. Tissues that
      included early nodules (1 month, ENT-1), persistent nodules (5 months, ENT-5),
      dissected HCC (12 months), and normal livers (NL) from adult rats were analyzed
      by cDNA arrays including 1185 rat genes. Differential genes were derived in each
      type of sample (n = 3) by statistical analysis. The relationship between samples
      was described in a Venn diagram for 290 genes. From these, 72 genes were shared
      between tissues with nodules and HCC. In addition, 35 genes with statistical
      significance only in HCC and with extreme ratios were identified. Differential
      expression of 11 genes was confirmed by comparative reverse transcription
      polymerase chain reaction, whereas that of 2 genes was confirmed by
      immunohistochemistry. Members involved in cytochrome P450 and second-phase
      metabolism were downregulated, whereas genes involved in glutathione metabolism
      were upregulated, implicating a possible role of glutathione and oxidative
      regulation. We provide a gene expression profile related to the progression of
      nodules into HCC, which contributes to the understanding of liver cancer
      development and offers the prospect for chemoprevention strategies or early
      treatment of HCC.

PMID- 16790088
TI  - CCI-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism
      linked to the targeting of mTOR/Hif-1alpha/VEGF signaling.
AB  - Angiogenesis is one of the critical steps in tumor growth and metastasis. The
      goal of this study was to evaluate whether the antitumor activity of CCI-779 is
      related to antiangiogenic effects in vivo in tumors of mice bearing human
      rhabdomyosarcoma (RMS) xenografts. We now demonstrate that CCI-779 rapidly
      inhibits mTOR activity, as indicated by S6 reduction and eukaryotic initiation
      factor 4E-binding protein 1 (4E-BP1) phosphorylation in two xenograft models of
      RMS within 24 hours of treatment. Treatment with a single 20-mg/kg dose of CCI
      779 suppressed S6 phosphorylation for more than 72 hours and 4E-BP1
      phosphorylation for more than 96 hours. Based on these data, an intermittent
      treatment schedule (every 3 days for 30 days) was chosen and displayed a
      significant suppression of both tumor growth and mTOR signaling. Western blot
      analysis and immunohistochemical studies demonstrated that the antitumor activity
      of CCI-779 was associated with antiangiogenesis, as indicated by impaired levels
      of hypoxia-inducible factor-1alpha (Hif-1alpha) and vascular endothelial growth
      factor (VEGF) protein expression and by decreased microvessel density in Rh30 and
      RD xenografts. Together, these data suggest that CCI-779 inhibits human RMS
      xenograft growth by an antiangiogenic mechanism associated with the targeting of
      mTOR/Hif-1alpha/VEGF signaling.

PMID- 16790087
TI  - The antimelanoma immunocytokine scFvMEL/TNF shows reduced toxicity and potent
      antitumor activity against human tumor xenografts.
AB  - The immunocytokine scFvMEL/TNF, a fusion protein composed of human tumor necrosis
      factor (TNF) and a single-chain Fv antibody (scFv) scFvMEL targeting the melanoma
      gp240 antigen, demonstrates impressive cytotoxic effects against human melanoma
      cell lines in vitro. Pharmacokinetic studies of 125I-scFvMEL/TNF in BALB/c mice
      showed that the construct clears from the circulation with a terminal-phase half
      life of 17.6 hours after intravenous administration. The maximum tolerated dose
      of scFvMEL/TNF in nude mice was 4 mg/kg, i.v., on a daily x5 schedule. There were
      no changes in gross pathology, clinical chemistry, or hematologic parameters in
      mice treated at doses of up to 3 mg/kg. Therapeutic studies at a dose of 2.5
      mg/kg on athymic mice bearing established (approximately 50 mm3) human melanoma
      A375GFP xenograft tumors transfected with green fluorescent protein demonstrated
      potent tumor suppression and complete tumor regression of all lesions. There was
      no subsequent outgrowth of tumors from mice rendered tumor-free. These data show
      that scFvMEL/TNF can target melanoma cells in vivo and can result in pronounced
      antimelanoma effects after systemic administration. Toxicology studies indicate
      the relative safety of this agent at doses that are therapeutically effective and
      provide guidance to projected phase I starting doses on patients at this
      schedule.

PMID- 16790089
TI  - Cardenolide-induced lysosomal membrane permeabilization demonstrates therapeutic
      benefits in experimental human non-small cell lung cancers.
AB  - Non-small cell lung cancers (NSCLCs) are the leading cause of cancer deaths in
      most developed countries. Targeting heat shock protein 70 (Hsp70) expression and
      function, together with the induction of lysosomal membrane permeabilization
      (LMP), could overcome the multiple anti-cell death mechanisms evidenced in NSCLCs
      that are responsible for the failure of currently used chemotherapeutic drugs.
      Because cardenolides bind to the sodium pump, they affect multiple signaling
      pathways and thus have a number of marked effects on tumor cell behavior. The aim
      of the present study was to characterize in vitro and in vivo the antitumor
      effects of a new cardenolide (UNBS1450) on experimental human NSCLCs. UNBS1450 is
      a potent source of in vivo antitumor activity in the case of paclitaxel-and
      oxaliplatin-resistant subcutaneous human NCI-H727 and orthotopic A549 xenografts
      in nude mice. In vitro UNBS1450-mediated antitumor activity results from the
      induction of nonapoptotic cell death. UNBS1450 mediates the decrease of Hsp70 at
      both mRNA and protein levels, and this is at least partly due to UNBS1450-induced
      downregulation of NFAT5/TonEBP (a factor responsible for the transcriptional
      control of Hsp70). These effects were paralleled by the induction of LMP, as
      evidenced by acridine orange staining and immunofluorescence analysis for
      cathepsin B accumulation.

PMID- 16790090
TI  - Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit
      B of protein phosphatase 2 PPP2R2A in childhood teratoma.
AB  - We characterized the molecular genetic consequences of a balanced chromosome
      translocation t(8;22)(p21;q12), which occurred as the sole cytogenetic aberration
      in short-term cultured cells from an intrathoracic mature teratoma in a 15-year
      old girl. Fluorescence in situ hybridization and reverse transcription-polymerase
      chain reaction disclosed that t(8;22) resulted in the fusion of the genes PPP2R2A
      and CHEK2, with an inserted fragment belonging to class I endogenous retrovirus
      related sequences at the junction. Sequencing of the two genes did not reveal any
      additional mutation. None of the three detected PPP2R2A/CHEK2 fusion transcripts
      resulted in an in-frame PPP2R2A/CHEK2 chimerical open reading frame; however, in
      all of them, the known open reading frame of CHEK2 was preserved. Thus, promoter
      swapping leading to deregulated CHEK2 expression would be the most likely
      oncogenic mechanism. Whereas inactivating mutations of CHEK2 previously have been
      described in a variety of sporadic tumors and in inherited cancer-predisposing
      syndromes, PPP2R2A, encoding a regulatory subunit of the multimeric enzyme
      phosphatase 2, has not been directly implicated in tumorigenesis. Our findings
      suggest that deregulation of CHEK2 and/or PPP2R2A is of pathogenetic importance
      in at least a subset of germ cell tumors.

PMID- 16790094
TI  - Genetic and environmental origins of obesity relevant to reproduction.
AB  - Obesity has a negative impact on reproductive health, particularly in women with
      polycystic ovarian syndrome (PCOS). Obesity itself is the product of both genetic
      and environmental influences, although the current 'epidemic' of obesity is
      largely related to changes in diet and lifestyle. Single gene defects leading to
      obesity and disordered reproductive function are rare but can are informative
      about metabolic pathways involved in appetite regulation. There is good evidence
      that PCOS has an important genetic background, which probably involves the
      interaction of several genes. The phenotype of PCOS and its impact on
      reproductive function is profoundly affected by obesity, which, in turn has both
      genetic and environmental influences. Understanding the genetic basis of PCOS is
      important but improvements in diet and lifestyle are the best means of improving
      reproductive function.

PMID- 16790091
TI  - Sustained angiopoietin-2 expression disrupts vessel formation and inhibits glioma
      growth.
AB  - Systematic analyses of the expression of angiogenic regulators in cancer models
      should yield useful information for the development of novel therapies for
      malignant gliomas. In this study, we analyzed tumor growth, vascularization, and
      angiopoietin-2 (Ang2) expression during the development of U-87 MG xenografts. We
      found that tumoral angiogenesis in this model follows a multistage process
      characterized by avascular, prolific peripheral angiogenesis, and late vascular
      phases. On day 4, we observed an area of central necrosis, a peripheral ring of
      Ang2-positive glioma cells, and reactive Ang2-positive vascular structures in the
      tumor/brain interface. When the tumor had developed a vascular network, Ang2 was
      expressed only in peripheral vascular structures. Because Ang2 expression was
      downmodulated in the late stages of development, probably to maintain a stable
      tumoral vasculature, we next studied whether sustained Ang2 expression might
      impair vascular development and, ultimately, tumor growth. Ang2 prevented the
      formation of capillary-like structures by and impaired angiogenesis in a
      chorioallantoic membrane chicken model. Finally, we tested the effect of
      sustained Ang2 expression on U-87 MG xenograft development. Ang2 significantly
      prolonged the survival of intracranial U-87 MG tumor-bearing animals. Examination
      of Ang2-treated xenografts revealed areas of tumor necrosis and vascular damage.
      We therefore conclude that deregulated Ang2 expression during gliomagenesis
      hindered successful angiogenesis and that therapies that sustain Ang2 expression
      might be effective against malignant gliomas.

PMID- 16790095
TI  - Diet around conception and during pregnancy--effects on fetal and neonatal
      outcomes.
AB  - Substrate supply to the fetus is a major regulator of prenatal growth. Maternal
      nutrition influences the availability of nutrients for transfer to the fetus.
      Animal experiments demonstrate that restriction of maternal protein or energy
      intake can retard fetal growth. Effects of maternal nutrition vary with the type
      and timing of the restriction and the species studied. Maternal undernutrition
      before conception and/or in early pregnancy can alter fetal physiology in late
      gestation, and influence postnatal function, often without measurable effects on
      birth size. In contrast, to date, observational and intervention studies in
      humans provide limited support for a major role of maternal nutrition in
      determining birth size, except where women are quite malnourished. However,
      recent studies report associations between newborn size and the balance of
      macronutrients in women's diets in Western settings. Associations between
      maternal dietary composition and adult blood pressure of the offspring are also
      reported in human populations. Most studies in women have focused on dietary
      content or supplementation during mid-late pregnancy. Further investigation of
      how maternal dietary composition, before conception and throughout pregnancy,
      affects fetal physiology and health of the baby will increase the understanding
      of how maternal diet and nutritional status influence fetal, neonatal and longer
      term outcomes.

PMID- 16790096
TI  - Metabolic effects of obesity on reproduction.
AB  - Obese women are characterized by similar comorbidities to men, particularly type
      2 diabetes mellitus and cardiovascular diseases. Moreover, they also develop some
      specific problems, including fertility-related disorders and some hormone
      dependent forms of cancer. The relationship between excess body fat and
      reproductive disturbances appears to be stronger for early-onset obesity. Early
      onset of obesity, particularly during adolescence, favours the development of
      menses irregularities, chronic oligo-anovulation and infertility in adulthood.
      Moreover, obesity in women can increase the risk of miscarriage and impair the
      outcome of assisted reproductive technologies. The main factor implicated in the
      association between obesity and fertility-related disorders is insulin excess,
      which accompanies insulin resistance. Hyperinsulinaemia may be directly
      responsible for the development of androgen excess, through its effects in
      reducing sex hormone-binding globulin synthesis and circulating concentrations,
      and in stimulating ovarian androgen production rates. Androgen excess, in turn,
      represents one of the major factors leading to altered ovarian physiology and
      associated ovulatory disturbances. Obesity-associated hyperleptinaemia may
      represent an additional factor involved in anovulation, not only through the
      induction of insulin resistance, but also through a direct impairment of ovarian
      function.

PMID- 16790098
TI  - Evidence for effects of weight on reproduction in women.
AB  - Body weight, and its constituent components of fat mass and lean tissue, plays an
      important role modulating reproductive development and functioning. Body weight
      influences the timing of menarche and the capacity to achieve a pregnancy. The
      nature of this relationship appears to be some variant on a 'U' shape. Extremes
      in body weight are associated with infertility and a range of adverse outcomes
      for both mother and baby across the course of pregnancy and perinatal period.
      Whereas underweight is associated with poor fetal growth and elevated pregnancy
      loss, overweight is more strongly associated with diseases in pregnancy,
      pregnancy loss and stillbirth and high birth weight. An emerging area of interest
      is the role of obesity on fertility, and the intergenerational 'tracking' of high
      maternal body weight into the second and subsequent generations, resulting not
      only in an increased risk of metabolic disease, but also perturbed reproductive
      functioning in the offspring.

PMID- 16790099
TI  - Obesity and assisted reproductive technology outcomes.
AB  - Obesity is a rising health problem in Western societies. It has been related to
      increased morbidity and mortality rates due to several pathologies. In the field
      of gynaecology and reproduction, obesity is associated with menstrual disorders,
      hirsutism, infertility, miscarriage and obstetric complications. It is known to
      impair human reproduction through different mechanisms such as insulin
      resistance, hyperandrogenism and elevated leptin levels. Weight management and
      dietary intervention can reverse this situation and improve reproductive
      function. Obesity can also impair the outcome of assisted reproductive
      technologies. The lower probability of a healthy live birth described in obese
      women seems to be the result of a combination of lower implantation and pregnancy
      rates, higher preclinical and clinical miscarriage rates and increased
      complications during pregnancy for both mother and fetus. Studies performed in
      infertile women undergoing assisted reproduction technologies indicate that the
      ovary plays a leading, but not exclusive, role in the fertility prognosis of
      these patients. The endocrine and metabolic environment may affect oocyte quality
      and, therefore, embryo development, implantation and pregnancy outcome. The
      endometrium seems to play a subtle role in the more negative reproductive outcome
      of obese women, according to recent studies based on the ovum donation model.

PMID- 16790100
TI  - Effects of lifestyle modification in polycystic ovarian syndrome.
AB  - Polycystic ovarian syndrome (PCOS) is a common endocrine condition with
      reproductive and metabolic consequences, including anovulation, infertility and
      an increased prevalence of diabetes mellitus. Obesity, central obesity and
      insulin resistance are strongly implicated in its aetiology. Dietary weight loss
      is recommended as the primary treatment strategy; however, effective means of
      achieving and maintaining weight loss and reproductive and metabolic improvements
      are unknown. Lifestyle modification programmes with an emphasis on behavioural
      management and dietary and exercise interventions have been successful in the
      general population in reducing the risk of diabetes and the metabolic syndrome,
      and have had some initial success in improving fertility outcomes in PCOS.
      However, the literature on effective diet and exercise programmes for PCOS has
      been sparse, and structured advice for implementing components of lifestyle
      modification programmes should be assessed in this population.

PMID- 16790101
TI  - Physical activity and its effects on reproduction.
AB  - The reproductive system is tightly coupled with energy balance, and thereby
      changes in the status of energy balance through changes in physical activity can
      impact on the reproductive system. In light of the new physical activity for
      health recommendations, it is therefore important to understand the inherent
      effects, both positive and negative, of physical activity on the reproductive
      system. At both extremes of the energy spectrum, disorders of chronic energy
      excess and energy deficiency are characterized by a wide range of reproductive
      disorders, including menstrual irregularity, anovulation, polycystic ovarian
      syndrome, and infertility in women, and erectile dysfunction and altered
      spermatogenesis in men. Although laboratory research indicates that individuals
      may be able to prevent or reverse reproductive disruptions, either by increasing
      energy expenditure in cases of energy excess or by dietary reform in cases of
      energy deficits, there is an acute need for applied research to confirm this idea
      and to identify mechanisms by which the availability of energy per se regulates
      reproductive function in humans.

PMID- 16790102
TI  - An evolutionary concept of polycystic ovarian disease: does evolution favour
      reproductive success over survival?
AB  - Polycystic ovarian disease (PCOD) is currently considered as possibly the most
      frequent cause of female infertility. It is also closely associated with syndrome
      XX, which, in turn, is closely linked with premature and excessive mortality.
      Considering these adverse effects on reproductive success and human survival, the
      evolutionary survival of PCOD, itself considered by many to be a genetically
      transmitted condition, would, on first glance, appear surprising, since evolution
      usually discriminates against both of these traits. However, an analysis of some
      recently reported characteristics of the condition calls for the reconsideration
      of PCOD as a condition which, from an evolutionary viewpoint, favours decreased
      reproductive success. Indeed, the reported observations that patients with PCOD
      will resume spontaneous ovulation with even relatively minor weight loss, and
      experience later menopause than controls, suggests exactly the opposite. Under an
      evolutionary concept, PCOD can thus be seen as a 'fertility storage condition'
      which in fact favours human reproductive success and allows the human species to
      maintain fertility even during adverse environmental circumstances, such as
      famines.

PMID- 16790104
TI  - Effects of culture medium on HCG concentrations and their value in predicting
      successful IVF outcome.
AB  - The hypothesis was tested that the medium used to culture embryos affects the
      concentration of human chorionic gonadotrophin (HCG) early in pregnancy. The
      value of these concentrations in predicting successful outcome was also assessed
      for each medium studied. Patients undergoing IVF between January 1998 and
      December 2004 and having a day 3 embryo transfer were stratified into one of four
      groups according to the medium in which their embryos were cultured (P1, IVF500,
      G1.2, and G1.3). Using receiver operating characteristic (ROC) curve analysis,
      cut-off values for serum HCG concentrations on day 15 after embryo transfer were
      calculated for optimal discrimination between cycles resulting in implantation
      failure and success for each medium. Cut-off points were chosen to maximize
      sensitivity and specificity. For viable singleton pregnancies, mean HCG
      concentrations were greater for G1.3 and lower for IVF500 compared with the other
      media. Discriminatory HCG cut-off concentrations for predicting implantation
      success were lowest for IVF500, intermediate for P1 and G1.2 and highest for
      G1.3. The data support the hypothesis that the medium used to culture embryos
      significantly affects the concentrations of HCG early in pregnancy. Furthermore,
      when using HCG cut-off concentrations to assess pregnancy outcome, medium type
      should be taken into consideration.

PMID- 16790105
TI  - Outlook: who needs LH in ovarian stimulation?
AB  - LH plays a key role in the intermediate-late phases of folliculogenesis. Although
      ovarian stimulation is efficiently achieved in most cases by the administration
      of exogenous FSH alone, specific subgroups of women may benefit from LH activity
      supplementation during ovarian stimulation. Some authors have found improved
      outcome with LH activity supplementation in advanced reproductive age women.
      Experience suggests that in about 10-12% of young normogonadotrophic patients
      treated with a gonadotrophin-releasing hormone agonist (GnRH-a) long protocol
      plus recombinant FSH human (r-hFSH), a 'steady response' is observed. In this
      subgroup of women, a higher number of oocytes is retrieved when daily LH activity
      supplementation is given from stimulation day 8, if compared with the standard
      FSH dose increase. Another subgroup of patients who may benefit from LH activity
      supplementation are those at risk for poor ovarian response treated with GnRH
      antagonist. Recent data demonstrate that in these women, when GnRH is
      administered in a flexible protocol, the concomitant addition of recombinant
      human LH improves the number of mature oocytes retrieved, when compared with the
      standard GnRH-a flare-up protocol. Thus, well calibrated LH administration
      improves the ovarian outcome in patients >35 years, in those showing an initial
      abnormal ovarian response to r-hFSH monotherapy, and in 'low prognosis' women
      treated with GnRH antagonists.

PMID- 16790106
TI  - Effect of oocyte morphology on embryo development and implantation.
AB  - Assessment of oocyte morphology is a difficult task, since underlying mechanisms
      that change the appearance of the oocyte are multifactorial and complex.
      Significant morphological variations are known to exist among oocytes that may
      affect the developmental competence and implantation potential of the derived
      embryo. Morphological variations of the oocyte may result from intrinsic factors
      such as age and genetic defects or extrinsic factors such as stimulation
      protocols, culture conditions, and nutrition. The effect of these morphological
      variations of the oocyte on embryo development and implantation, however, is not
      conclusively defined because of methodological flaws inherent to most of the
      studies in the literature. This review will mainly discuss morphological markers
      of oocyte quality/viability in relation to the oocyte morphology and attempt to
      clarify whether morphological evaluation of the oocyte can be utilized for
      predicting the implantation potential of the derived embryo.

PMID- 16790107
TI  - Paternal and maternal factors in preimplantation embryogenesis: interaction with
      the biochemical environment.
AB  - Paternal effect on embryonic development occurs as early as fertilization.
      Incorrect formation of the spermatozoon due to centrosome defects and abnormal
      concentrations of any components involved in the activation process lead to
      failure immediately or in the subsequent cell cycles. Sperm chromosomal
      abnormalities result in early embryo developmental arrests. Generally poor
      spermatozoa lead to poor blastocyst formation. Sperm DNA fragmentation may impair
      even late post-implantation development. The DNA repair capacity of the oocytes
      is of major importance. Early preimplantation development, i.e. until maternal to
      zygotic transition, is maternally driven. Maternal mRNAs and proteins are of
      major importance, as there is an unavoidable turnover of these reserves.
      Polyadenylation of these mRNAs is precisely controlled, in order to avoid too
      early or too late transcription and translation of the housekeeping genes. An
      important set of maternal regulations, such as DNA stability, transcriptional
      regulation and protection against oxidative stress, are impaired by age. The
      embryo biochemical endogenous pool is very important and may depend upon the
      environment, i.e. the culture medium. Paternal, maternal and environmental
      factors are unavoidable parameters; they become evident when age impairs oocyte
      quality.

PMID- 16790109
TI  - Developmentally retarded frozen blastocysts can be rescued by synchronizing
      culture prior to transfer.
AB  - Asynchrony between embryo development and endometrial differentiation is the
      limiting step of successful pregnancy in assisted reproduction. The aim of this
      study was to investigate whether or not post-thaw synchronization culture of day
      5-6 frozen embryos, prior to transfer, with endometrial differentiation resulted
      in pregnancy. A total of 142 cycles of 134 patients were transferred in three
      protocols. Blastocysts with cavities larger than half of the entire blastocyst
      volume were transferred without synchronizing culture on day 5 or 6 of
      progesterone commencement (P5/6) in hormone replacement treatment cycles
      (protocol 1). Blastocysts with cavitation below half of the entire blastocyst
      were cultured for 1 or 2 days after thawing prior to transfer on P5 or P6
      (protocol 2). Morulae and very early stage blastocysts were thawed on the days
      corresponding to P5 and P6, and only the embryos that reached expanded or
      hatching blastocysts were transferred on P7 without synchronizing culture
      (protocol 3). Pregnancy rate in protocol 2 (32.0%) was comparable with that of
      protocol 1 (35.0%). It is concluded that developmentally retarded frozen embryos
      can be rescued with synchronizing culture prior to transfer by evading
      asynchrony.

PMID- 16790111
TI  - Relationship between oxidative stress, varicocele and infertility: a meta
      analysis.
AB  - Varicocele is one of the leading causes of male infertility, and is present in
      almost 40% of infertile males. Recent understanding of the role of oxidative
      stress in male reproduction has led some researchers to postulate oxidative
      stress as the possible cause of sperm dysfunction in varicocele patients. The
      objective of the present study was to examine the published literature on the
      role of oxidative stress in patients with varicocele as the aetiology of their
      infertility. Twenty-three human studies were identified after an extensive search
      dealing with the role of oxidative stress in varicocele-associated infertility.
      Out of these studies, four were selected that measured similar types of reactive
      oxygen species (ROS) by a similar method of measurement. The data were then
      entered in the RevMan software for analysis. The overall estimate showed that
      patients have significantly higher concentrations of ROS than controls, with the
      mean difference being 0.73 (95% CI 0.40, 1.06, P < 0.0001). This translated to an
      ROS concentration of 4.37 x 10(4) cpm/20 x 10(6) spermatozoa/ml on the linear
      scale. Total antioxidant capacity levels were found to be significantly lower in
      the infertile varicocele patients, with 386 fewer trolox equivalents than the
      controls (95% CI -556.56-216.96, P < 0.00001). From the results, it can be
      concluded that there is increased oxidative stress in varicocele patients;
      however, more studies are needed to confirm this finding.

PMID- 16790113
TI  - How to improve IVF-ICSI outcome by sperm selection.
AB  - In previous studies, a new IVF method of intracytoplasmic morphologically
      selected sperm injection (IMSI) was introduced, based on motile sperm organellar
      morphology examination (MSOME). It was concluded that microinjection of
      morphologically selected sperm cells with strictly normal nucleus, defined by
      MSOME, improves IVF-ICSI outcome. The aim of the present study was to confirm
      this conclusion in new, enlarged study groups. Comparison between 80 couples, who
      underwent an IVF-IMSI trial, with matched couples, who underwent a standard IVF
      ICSI procedure, confirmed that pregnancy rate following IVF-IMSI was
      significantly higher, and abortion rate significantly lower than in the routine
      IVF-ICSI (60.0 versus 25.0%, and 14 versus 40% respectively, P <or= 0.05).
      Another comparison was performed between matched IMSI groups, where embryos were
      obtained from microinjection by spermatozoa with a morphologically normal nucleus
      ('best' group, n = 70) and a 'second best' group was selected, where embryos were
      obtained from microinjection of spermatozoa with minimal morphological
      impairment, since no other sperm cells were available. It was confirmed that
      microinjection by 'second best ' spermatozoa result in significantly lower
      pregnancy and delivery rates and significantly higher abortion rates than
      microinjection with 'best' spermatozoa (25.7 versus 58.2%, P <or= 0.01; 17.1
      versus 52.8%, P <or= 0.01, and 33.3 versus 9.7%, P <or= 0.02 respectively). The
      present study has strengthened previous conclusions.

PMID- 16790114
TI  - Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study.
AB  - The study was conducted to investigate the effect of conservative surgery of
      ovarian endometriomas before an ICSI cycle. Ninety-nine patients with
      endometriomas who were referred to an intracytoplasmic sperm injection (ICSI)
      cycle were enrolled in the study. The patients were prospectively randomized into
      two groups; group I (49 patients) underwent conservative ovarian surgery before
      the ICSI cycle and group II (50 patients) underwent the ICSI cycle directly. The
      stimulation was started 3 months after the operation in group I and directly in
      group II. In the ovarian surgery group, stimulation was significantly longer
      (14.0 days in group I and 10.8 days in group II; P = 0.001), total recombinant
      FSH dose was significantly higher (4575 IU in group I and 3675 IU in group II; P
      = 0.001), and mean number of mature oocytes was significantly lower (7.8 in group
      I and 8.6 in group II; P = 0.032). There was no difference in terms of
      fertilization (86% in group I and 88% in group II), implantation (16.5% in group
      I and 18.5% in group II) and pregnancy rates (34% in group I and 38% in group
      II). Ovarian surgery resulted in longer stimulation, higher FSH requirement and
      lower oocyte number, but fertilization, pregnancy and implantation rates did not
      differ between the groups.

PMID- 16790116
TI  - Embryo transfer: one or two?

PMID- 16790117
TI  - Long-term effects of gamete donation.

PMID- 16790118
TI  - Spinal neurenteric cyst presenting as recurrent midline sebaceous cysts.
AB  - A 59-year-old patient had been treated by the general surgery department at her
      local hospital for a recurrent sebaceous cyst on the back of her neck. Cervical
      MRI showed a cystic structure, posterior to fused vertebral bodies, connected to
      the skin by a sinus passing through the middle of a split cord malformation. The
      lesion was excised via an anterior approach. Histology confirmed a benign
      neurenteric cyst. This rare developmental anomaly, mimicking a common acquired
      surgical condition, highlights the need for caution in the diagnosis of midline
      pathology.

PMID- 16790119
TI  - Stress fracture of the clavicle in a patient with no obvious risk factors.
AB  - A 28-year-old woman presented with right shoulder pain and, after a delay, a
      diagnosis of clavicular stress fracture was made. The patient gave no history of
      repetitive abnormal loading of the upper limbs which could have assisted the
      diagnosis. The authors wish to raise awareness of this rare diagnosis such that
      it can be considered in the differential for shoulder pain of unclear origin.

PMID- 16790120
TI  - Pyomyositis of the piriformis muscle in a juvenile.
AB  - The authors present a case of pyomyositis of the piriformis muscle. This case,
      the first in the English speaking literature of piriformis involvement in a
      juvenile, serves to illustrate the need for a high index of suspicion when
      treating children with symptoms related to impalpable pathology deep in the
      pelvis and the usefulness of MRI in early diagnosis and treatment before abscess
      formation. It also shows the potentially wide differential diagnosis in which the
      signs and symptoms may be misleading due to the close relationship of the pelvic
      muscles with the hip joint and adjacent viscera.

PMID- 16790121
TI  - Annular pancreas - a rare cause of gastric obstruction in an 82-year-old patient.
AB  - Annular pancreas is an uncommon and rarely reported congenital anomaly and thus
      is rarely suspected. A case is reported of an 82-year-old patient who presented
      with a 3-month history of nausea and vomiting associated with weight loss who at
      laparotomy was found to have an annular pancreas.

PMID- 16790122
TI  - Controversial topics in surgery. The case for laparoscopic repair.

PMID- 16790125
TI  - Hydatid disease of the heart.
AB  - A 27-year-old physical education teacher, from a rural sheep farming area of
      South Africa, was referred following an isolated episode of collapse.
      Transthoracic echocardiography and MRI showed a cystic lesion under the septal
      leaflet of the tricuspid valve attached to the right ventricular wall. A
      provisional diagnosis of hydatid cyst was made. Hydatid serology was negative and
      there was no evidence of hydatidosis elsewhere. Preoperatively, the patient was
      treated with praziquantel and albendazole. Surgery was performed using
      cardiopulmonary bypass. Cyst was excised without any spillage. The patient was
      weaned off bypass without any support and made an uneventful recovery. Cytology
      and microbiology of the specimen confirmed hydatid pathology. This case describes
      excision of a right ventricular hydatid with techniques used to avoid spillage.
      It also describes an up-to-date antihelminthic therapy used in the management of
      hydatid cysts.

PMID- 16790126
TI  - Screening for prostate cancer.

PMID- 16790127
TI  - The case against.

PMID- 16790129
TI  - NICE news in the Annals.

PMID- 16790135
TI  - The Annals - fit for purpose?

PMID- 16790137
TI  - Controversial topics in surgery. Radical prostatectomy.

PMID- 16790138
TI  - NICE news in the Annals.

PMID- 16790140
TI  - Can performance as an undergraduate assist entry selection into surgical training
      programmes?

PMID- 16790141
TI  - Advances in statistical models and methods.

PMID- 16790142
TI  - Advances in behavioral genetics modeling using Mplus: applications of factor
      mixture modeling to twin data.
AB  - This article discusses new latent variable techniques developed by the authors.
      As an illustration, a new factor mixture model is applied to the monozygotic
      dizygotic twin analysis of binary items measuring alcohol-use disorder. In this
      model, heritability is simultaneously studied with respect to latent class
      membership and within-class severity dimensions. Different latent classes of
      individuals are allowed to have different heritability for the severity
      dimensions. The factor mixture approach appears to have great potential for the
      genetic analyses of heterogeneous populations. Generalizations for longitudinal
      data are also outlined.

PMID- 16790143
TI  - Implementation of a combined association-linkage model for quantitative traits in
      linear mixed model procedures of statistical packages.
AB  - A transmission disequilibrium test for quantitative traits which combines
      association and linkage analyses is currently available in several dedicated
      software packages. We describe how to implement such models in linear mixed model
      procedures that are available in widely used statistical packages such as SPSS.
      We also briefly mention a few extensions of the model that become naturally
      available once the model is implemented in such procedures.

PMID- 16790144
TI  - Fitting genetic models using Markov Chain Monte Carlo algorithms with BUGS.
AB  - Maximum likelihood estimation techniques are widely used in twin and family
      studies, but soon reach computational boundaries when applied to highly complex
      models (e.g., models including gene-by-environment interaction and gene
      environment correlation, item response theory measurement models, repeated
      measures, longitudinal structures, extended pedigrees). Markov Chain Monte Carlo
      (MCMC) algorithms are very well suited to fit complex models with hierarchically
      structured data. This article introduces the key concepts of Bayesian inference
      and MCMC parameter estimation and provides a number of scripts describing
      relatively simple models to be estimated by the freely obtainable BUGS software.
      In addition, inference using BUGS is illustrated using a data set on follicle
      stimulating hormone and luteinizing hormone levels with repeated measures. The
      examples provided can serve as stepping stones for more complicated models,
      tailored to the specific needs of the individual researcher.

PMID- 16790145
TI  - Latent curve analyses of longitudinal twin data using a mixed-effects biometric
      approach.
AB  - In a recent article McArdle and Prescott (2005) showed how simultaneous
      estimation of the biometric parameters can be easily programmed using current
      mixed-effects modeling programs (e.g., SAS PROC MIXED). This article extends
      these concepts to deal with mixed-effect modeling of longitudinal twin data. The
      biometric basis of a polynomial growth curve model was used by Vandenberg and
      Falkner (1965) and this general class of longitudinal models was represented in
      structural equation form as a latent curve model by McArdle (1986). The new mixed
      effects modeling approach presented here makes it easy to analyze longitudinal
      growth-decline models with biometric components based on standard maximum
      likelihood estimation and standard indices of goodness-of-fit (i.e., chi(2), df,
      epsilon(a)). The validity of this approach is first checked by the creation of
      simulated longitudinal twin data followed by numerical analysis using different
      computer programs (i.e., Mplus, Mx, MIXED, NLMIXED). The practical utility of
      this approach is examined through the application of these techniques to real
      longitudinal data from the Swedish Adoption/Twin Study of Aging (Pedersen et al.,
      2002). This approach generally allows researchers to explore the genetic and
      nongenetic basis of the latent status and latent changes in longitudinal scores
      in the absence of measurement error. These results show the mixed-effects
      approach easily accounts for complex patterns of incomplete longitudinal or twin
      pair data. The results also show this approach easily allows a variety of complex
      latent basis curves, such as the use of age-at-testing instead of wave-of
      testing. Natural extensions of this mixed-effects longitudinal approach include
      more intensive studies of the available data, the analysis of categorical
      longitudinal data, and mixtures of latent growth-survival/frailty models.

PMID- 16790146
TI  - Semiparametric maximum likelihood variance component estimation using mixture
      moment structure models.
AB  - Nonnormal phenotypic distributions introduce significant problems in the
      estimation and selection of genetic models. Here, a semiparametric maximum
      likelihood approach to analyzing nonnormal phenotypes is described. In this
      approach, distributions are explicitly modeled together with genetic and
      environmental effects. Distributional parameters are introduced through mixture
      constraints, where the distribution of effects are discretized and freely
      estimated rather than assumed to be normal. Semiparametric maximum likelihood
      estimation can be used with a variety of genetic models, can be extended to a
      variety of pedigree structures, and has various advantages over other approaches
      to modeling nonnormal data.

PMID- 16790147
TI  - Phenotypic factor analysis of family data: correction of the bias due to
      dependency.
AB  - Twin registries form an exceptionally rich source of information that is largely
      unexploited for phenotypic analyses. One obstacle to straightforward phenotypic
      statistical analysis is the inherent dependency, which is due to the clustering
      of cases within families. The present simulation study gauges the degree of the
      bias produced by the dependency of family data on the estimates of standard
      errors and chi-squared, when they are treated as independent observations in a
      phenotypic model, and assesses the efficiency of an estimator, which corrects for
      dependency. When family-clustered data are used for phenotypic analysis, in
      treating individuals as independent, and using standard maximum likelihood
      estimation, there is a tendency for the chi-square statistic to be overestimated,
      and the standard errors of the parameters to be underestimated. The bias
      increases with family resemblance, due to heritability or shared environment. The
      source of family resemblance -- either heritability (h(2)) and/or shared
      environment (c(2)) -- interacts with the composition of the sample. In the
      absence of c(2), samples with twins, parents and spouses show the lowest bias,
      whereas in the presence of c(2) samples with only twins show the lowest bias. In
      all conditions the bias remained below 15%. The use of the 'complex option'
      available in Mplus (clustering corrected robust maximum likelihood estimation)
      reduces the bias to the levels observed when only independent cases are
      considered. Thus with the use of robust estimates the bias due to family
      dependency becomes practically negligible in all conditions of dependency. In
      conclusion, the present study shows that the bias due to dependency in family
      data does not form a serious obstacle to phenotypic data analysis.

PMID- 16790148
TI  - Detecting genotype-environment interaction in monozygotic twin data: comparing
      the Jinks and Fulker test and a new test based on Marginal Maximum Likelihood
      estimation.
AB  - This article is concerned with the power to detect the presence of genotype by
      environment interaction (G x E) in the case that both genes and environment
      feature as latent (i.e., unmeasured) variables. The power of the test proposed by
      Jinks and Fulker (1970), which is based on regressing the absolute difference
      between the scores of monozygotic twins on the sums of these scores, is compared
      to the power of an alternative test, which is based on Marginal Maximum
      Likelihood (MML). Simulation studies showed that generally the power of the MML
      based test was greater than the power of the Jinks and Fulker test in detecting
      linear and curvilinear G x E interaction, regardless of whether the distribution
      of the data deviated significantly from normality. However, after a normalizing
      transformation, the Jinks and Fulker test performed slightly better. Some
      possible future extensions of the MML-based test are briefly discussed.

PMID- 16790149
TI  - Effects of angiotensinogen and angiotensin II type I receptor genes on blood
      pressure and left ventricular mass trajectories in multiethnic youth.
AB  - The objective of this study was to evaluate the impact of variations of the
      angiotensinogen (AGT) and angiotensin II type I receptor (AGTR1) genes on
      progression of blood pressure (BP) and left ventricular mass (LVM) in multiethnic
      youth. The study was longitudinal involving 581 European American (EA) and
      African American (AA) youth with 12 assessments over a 15-year period. AGT M235T
      and three AGTR1 polymorphisms (C-521T, L191L and A1166C) were genotyped and
      individual growth curve modeling analyses were conducted. Single nucleotide
      polymorphism (SNP) analyses found a significant 3-way interaction between M235T,
      ethnicity and gender on BP levels. Systolic BP (SBP) levels were 5.8 mmHg (p =
      .00003) and diastolic BP (DBP) levels were 2.6 mmHg (p = .005) lower in carriers
      versus noncarriers of the M235 allele in AA males only. Furthermore, the AGTR1
      L191 allele showed a SBP lowering effect in subjects with a high socioeconomic
      status (SES;p = .048) and a DBP lowering effect in AAs (p = .038). Haplotype
      analyses identified a protective haplotype (C-521, 191L and A1166) for LVM levels
      (p = .03). LVM in individuals homozygous for this haplotype was 12.9 g lower than
      those homozygous for the most common haplotype (-521T, 191L and A1166). No
      significant interactions were found between the AGT M235T polymorphism and any of
      the single SNPs or haplotypes of the AGTR1 gene. Our results in multiethnic youth
      uncover an ethnicity and gender-specific effect of the AGT M235T polymorphism and
      a SES or ethnicity-specific effect of the AGTR1 L191L polymorphism on the
      progression of hypertension risk. A protective AGTR1 haplotype for LVM was also
      identified.

PMID- 16790150
TI  - A test of the equal environment assumption (EEA) in multivariate twin studies.
AB  - In the classic twin design, estimation of genetic and environmental effects is
      based on the assumption that environmental influences are shared to the same
      extent by monozygotic and dizygotic twins (equal environment assumption, EEA). We
      explore the conditions in which the EEA can be tested based on multivariate
      phenotypic data. We focus on the test whether the correlation between shared
      environmental factors in dizygotic twins (r(C)) is less than 1. First, model
      identification was investigated analytically in Maple and Mx. Second, statistical
      power was examined in Mx. Third, the amount of bias caused by violation of the
      EEA was evaluated. Finally, applications to empirical data concern spatial
      ability in adolescents and aggression in children. Bivariate and trivariate
      models include several instances in which the EEA can be tested. The number of
      twin pairs that is needed to detect violation of the EEA with a statistical power
      of .80 (alpha = .05) varied between 508 and 3576 pairs for the situations
      considered. The bias in parameter estimates, given misspecification, ranged from
      5% to 34% for additive genetic effects, and from 4% to 34% for shared
      environmental effects. Estimates of the nonshared environmental effects were not
      biased. The EEA was not violated for spatial ability or aggression. Multivariate
      data provide sufficient information to test the validity of the EEA. The number
      of twin pairs that is needed is no greater than the number typically available in
      most twin registries. The analysis of spatial ability and aggression indicated no
      detectable violation of the EEA.

PMID- 16790151
TI  - A finite mixture model for genotype and environment interactions: detecting
      latent population heterogeneity.
AB  - Approaches such as DeFries-Fulker extremes regression (LaBuda et al., 1986) are
      commonly used in genetically informative studies to assess whether familial
      resemblance varies as a function of the scores of pairs of twins. While useful
      for detecting such effects, formal modeling of differences in variance components
      as a function of pairs' trait scores is rarely attempted. We therefore present a
      finite mixture model which specifies that the population consists of latent
      groups which may differ in (i) their means, and (ii) the relative impact of
      genetic and environmental factors on within-group variation and covariation. This
      model may be considered as a special case of a factor mixture model, which
      combines the features of a latent class model with those of a latent trait model.
      Various models for the class membership of twin pairs may be employed, including
      additive genetic, common environment, specific environment or major locus (QTL)
      factors. Simulation results based on variance components derived from Turkheimer
      and colleagues (2003), illustrate the impact of factors such as the difference in
      group means and variance components on the feasibility of correctly estimating
      the parameters of the mixture model. Model-fitting analyses estimated group
      heritability as .49, which is significantly greater than heritability for the
      rest of the population in early childhood. These results suggest that factor
      mixture modeling is sufficiently robust for detecting heterogeneous populations
      even when group mean differences are modest.

PMID- 16790152
TI  - Influences on achieving motor milestones: a twin-singleton study.
AB  - In order to determine if twinning impacted achievement of motor milestones the
      attainment of early motor milestones in twins was examined and compared to
      published data from singletons of the same age from the same culture and birth
      years. We examined the influence of twinning, sex, zygosity and birth cohort
      (1987-2001) on the motor development of twins aged 0 to 24 months. Data on the
      attainment of motor milestones (turn, sit, crawl, stand and walk) of twins were
      collected from maternal reports. All data were corrected for gestational age.
      Data from the twin sample were compared to normative data from singletons, which
      were available from Child Health Clinics (CHC). Analyses across twin data and the
      CHC singleton data revealed no differences between twins and singletons in
      achievement of motor milestones. Girls were able to sit without support slightly
      earlier than boys, otherwise there were no other sex differences. Birth-order
      analyses revealed minimal but significant differences in turning over from back
      to belly and for sitting without support between the first- and second-born.
      Dizygotic (DZ) twins were faster than monozygotic (MZ) twins in achieving the
      moment of sit, crawl, stand and walk. Twins born in earlier cohorts were faster
      in reaching the moment of crawl, sit and walk. It is concluded that there are no
      differences in time of reaching motor milestones between twins and singletons
      within the normal range. Sex has minimal to no effect on motor development in
      early childhood. DZ twins achieve motor milestones sooner than MZ twins.
      Attainment of gross motor milestones (crawl, stand and walk) is delayed in later
      birth cohorts.

PMID- 16790153
TI  - Muscle dissatisfaction and muscle-enhancing substance use: a population-based
      twin study in young adult men.
AB  - In the population-based Finn Twin 16 study, proportions of genetic and
      environmental factors contributing to muscle dissatisfaction and muscle-enhancing
      substance use were assessed in 319 pairs of twin brothers: 141 monozygotic (MZ)
      and 178 dizygotic (DZ) pairs. In addition there were 86 twin individuals from
      pairs in which only one co-twin responded. Of all respondents, 30% experienced
      high muscle dissatisfaction. The corresponding proportion of muscle-enhancing
      substance use was 10%. The subjects were similar in age (23.8 years, 95%
      confidence interval [CI] 23.76-23.84), body mass index (23.7, 95% CI 23.5-23.9),
      and waist circumference (84.5 cm, 95% CI 83.7-85.2), independent of their muscle
      dissatisfaction or muscle-enhancing substance use status and independent of their
      zygosity. The MZ polychoric correlation for muscle dissatisfaction was .39 (95%
      CI .17-.58) and .27 for DZ pairs (95% CI .07-.46). The MZ tetrachoric correlation
      for muscle-enhancing substance use was .65 (95% CI .28-.87) and .56 for DZ pairs
      (95% CI .26-.78). The AE model, where additive genetic factors (A) accounted for
      42% (95% CI .23-.59) and unique environmental factors (E) 58% (95% CI .41-.77) of
      the liability, provided the best fit for muscle dissatisfaction. The CE model,
      where common environmental factors (C) accounted for 60% (95% CI .37-.77) and
      unique environmental factors (E) 40% (95% CI .23-.63) of the liability, provided
      the best fit for muscle-enhancing substance use. Both genetic and unique
      (nonfamilial) environmental factors are involved in muscle dissatisfaction in the
      population. Nongenetic factors (both familial and nonfamilial) appear to best
      explain the use of muscle-enhancing substances.

PMID- 16790154
TI  - Perinatal outcomes with laser surgery for twin-twin transfusion syndrome.
AB  - The aim of this tertiary hospital-based cohort study was to determine and compare
      perinatal outcome and neonatal morbidities of pregnancies with twin-twin
      transfusion syndrome (TTTS) before and after the introduction of a treatment
      program with laser ablation of placental communicating vessels. Twenty-seven
      pregnancies with Stage II-IV TTTS treated with amnioreduction were identified
      (amnioreduction group). The data were compared with that obtained from the first
      31 pregnancies with Stage II-IV TTTS managed with laser ablation of placental
      communicating vessels (laser group). Comparisons were made for perinatal survival
      and neonatal morbidities including abnormalities on brain imaging. The median
      gestation at therapy was similar between the two groups (20 vs. 21 weeks, p =
      .24), while the median gestation at delivery was significantly greater in the
      laser treated group (34 vs. 28 weeks, p = .002). The perinatal survival rate was
      higher in the laser group (77.4% vs. 59.3%, p = .03). Neonatal morbidities
      including acute respiratory distress, chronic lung disease, requirement for
      ventilatory assistance, patent ductus arteriosus, hypotension, and oliguric renal
      failure had a lower incidence in the laser group. On brain imaging, ischemic
      brain injury was seen in 12% of the amnioreduction group and none of the laser
      group of infants (p = .01). In conclusion, these findings indicate that perinatal
      outcomes are improved with less neonatal morbidity for monochorionic pregnancies
      with severe TTTS treated by laser ablation of communicating placental vessels
      when compared to treatment by amnioreduction.

PMID- 16790155
TI  - Twins and their health cost: consequences of multiple births on parental health
      and mortality in Denmark and England and Wales.
AB  - The rapid increase in twinning rates in developed countries has increased
      interest in the question as to whether twin mothers have higher mortality and
      more health problems than mothers of singletons. Here we use a national survey,
      the Office for National Statistics Longitudinal Study of England & Wales, and a
      linkage between the Danish Twin Registry and the Danish population register to
      examine mortality patterns after age 45 (50 for fathers) for twin parents and the
      whole population born from 1911 to 1950. For England and Wales, presence of
      limiting long-term illnesses and self-rated health status was also investigated.
      Overall similar health and mortality was found for twin parents and the whole
      population although both life table methods and survival analysis suggested a
      slight excess mortality among older cohorts of twin mothers in England and Wales.

PMID- 16790156
TI  - The natural course of monochorionic and dichorionic twin pregnancies: a
      historical cohort.
AB  - Current early diagnosis, surveillance and intervention options make it hard to
      determine the natural course of twin pregnancies, especially regarding
      spontaneous preterm delivery and perinatal mortality. We studied the natural
      course in monochorionic (MC) and dichorionic (DC) twin pregnancies in a
      historical cohort. Twin pregnancies were studied in a unique database of 651 twin
      pairs born in the period 1907 to 1938. We examined the effect of chorionicity on
      gestational age, birthweight, perinatal mortality, intertwin birthweight
      differences, the incidence of preeclampsia and maternal mortality. Perinatal
      mortality was 27.7% for MC and 15.8% for DC twins (p < .001). Gestational age and
      birthweight were stronger predictors of perinatal mortality than chorionicity.
      Perinatal outcome was poorer for the second twin, especially in DC twins.
      Delivery before 37 weeks of gestation occurred more often in MC twin pregnancies
      (48.8% compared to 33.3% in DC twin pregnancies). DC twins were on average 288 g
      (95% confidence interval 201-376) heavier than MC twins. Severe birthweight
      discordancy occurred equally in MC and DC twins (18.1%). However, if present,
      mortality was only increased in MC twins. The birthweight of girls was not
      affected by the presence of a male co-twin. In this historical cohort MC twin
      pregnancies had a higher perinatal mortality, caused by a high incidence of low
      birthweight mainly due to preterm delivery. Mortality did not differ in
      deliveries after 31 weeks of gestation, which is in contrast to recent data.
      Apparently, modern obstetrics is more effective in reducing mortality in DC
      twins.

PMID- 16790157
TI  - Discordant fetal infection for parvovirus B19 in a dichorionic twin pregnancy.
AB  - There are only a few reports of fetal parvovirus infection in the circumstance of
      a twin pregnancy. We report a case of differential fetal infection following
      maternal parvovirus B19 infection in a dichorionic twin pregnancy culminating in
      a dual live-birth. A 32-year-old woman was diagnosed with parvovirus infection
      following exposure to her infected child at 19 weeks' gestation in a dichorionic
      twin gestation. Maternal IgG seroconversion was documented and maternal blood
      parvovirus B19 DNA was detected by PCR testing. Fetal monitoring with serial
      ultrasound assessment was instituted. At 25 weeks' gestation Twin I (male)
      displayed minor ascites, small pericardial effusion, placentomegaly and
      oligohydramnios. Middle cerebral artery peak systolic velocity (MCA PSV) studies
      were abnormal. Twin II (female) was sonographically unremarkable. A single fetal
      intravascular transfusion for Twin I was performed (pretransfusion Hb 80 g/L).
      Twin I fetal blood parvovirus B19 DNA was detected by polymerase chain reaction
      (PCR) and serum demonstrated both B19 IgG and IgM. Following fetal transfusion
      the hydrops resolved, although the placentomegaly persisted. Two live infants
      were delivered at 37 weeks' gestation. Individual neonatal venepuncture detected
      B19 DNA by PCR in Twin I but not in Twin II. B19 IgM was present in Twin I but
      not Twin II. Both neonates had B19 IgG antibodies. Placental histopathology
      demonstrated mild edema for Twin I but no inclusion cells. The placenta of Twin
      II was unremarkable. This case demonstrates the ability for differential
      transplacental infection of this virus and the assistance of fetal MCA flow
      studies to guide therapy in a multiple pregnancy at risk of parvovirus infection.

PMID- 16790158
TI  - Intrauterine growth and cerebral palsy in twins: a European multicenter study.
AB  - Population-based studies in twins have been of insufficient size to explore the
      relationship between risk of cerebral palsy and intrauterine growth. Earlier
      studies in singletons have suggested an optimum size at birth for minimum
      cerebral palsy risk between the 75th and 90th percentiles of weight for
      gestational age. We aggregated data from nine European cerebral palsy registers
      for 1976 to 1990. Using sex-specific fetal growth standards for twins, a z score
      of weight-for-gestation was derived for each of the 373 twin cases. The rates of
      cerebral palsy in each z-score band were compared to the rate in the a priori
      reference band of 0.67 to less than 1.28 (equivalent to the 75th to less than
      90th percentiles). In twins born at 32 weeks' gestation or more (92% of all
      twins), cerebral palsy rates were higher for both light and heavy-for-gestation
      babies compared to an optimum (i.e., minimum risk) in the reference band.
      However, the rate ratio for heavy babies (90th percentile or greater) did not
      reach conventional (95% confidence intervals [CI]) statistical significance (rate
      ratios = 1.76; 90% CI 1.02-3.03). For twins born at less than 32 weeks, the
      significantly higher risk for cerebral palsy was observed consistently in all z
      score bands less than average compared to the reference band. This multi-center
      study demonstrates that for twins born at 32 weeks' gestation or more, an
      increased risk of cerebral palsy is associated with deviations from optimal
      intrauterine growth at about 1 standard deviation above mean weight, as was
      earlier reported for singletons. For twins born at less than 32 weeks' gestation,
      this pattern is only demonstrable for babies weighing below the optimum weight
      for-gestation.

PMID- 16790159
TI  - The evolution of female orgasm: adaptation or byproduct?
AB  - Do women experience orgasm because this trait was shaped by natural selection to
      augment female fitness? Or are women merely the lucky recipients of developmental
      patterns favored by selection to produce orgasm in males? A recent and widely
      publicized book by Elisabeth Lloyd (2005a) contends that there is insufficient
      evidence to validate any of the adaptive explanations yet proposed for female
      orgasm. We agree. But our reading of the data differs from Lloyd's. In this
      essay, we outline why, unlike Caton (2006), whose review of Lloyd's book appeared
      previously in this journal, we are not persuaded by Lloyd's argument that female
      orgasm is a nonadaptive byproduct of orgasm in men. We hold this view because we
      disagree with the criteria Lloyd uses to evaluate evolutionary hypotheses, and
      because we believe Lloyd defines female orgasm too narrowly, ignoring critical
      information about its affective aspects.

PMID- 16790160
TI  - Same or separate classrooms: a twin bill.
AB  - New legislation giving parents a voice in deciding their twins' school placement
      situation (same or separate classrooms) was passed in Minnesota in spring 2005.
      Since then, parents in several other states have started petitions and lobbying
      efforts to persuade their senators and representatives to follow suit. A review
      and update of these exciting developments is presented.

PMID- 16790161
TI  - [Medical psychotherapy and psychosomatic medicine--joint responsibilities].

PMID- 16790162
TI  - [Psychosomatic aspects of bowel diseases].
AB  - Functional gastrointestinal disorders (FGID) and inflammatory bowel diseases
      (IBD) are the most frequently studied bowel disorders in the context of a bio
      psycho-social model. FGID are associated with significant work absenteeism,
      impaired quality of life, and increased medical costs. Many patients also suffer
      from psychosocial problems. Most of the research in FGID to date has focused on
      the irritable bowel syndrome. Randomised controlled studies have shown that
      psychotherapy is superior to conventional medical therapy. The gut-focussed
      hypnotherapy seems to be very successful. For IBD it is increasingly recognized
      that the psycho-neuro-endocrine network can modulate inflammation and pain
      perception and that psychosocial factors are related to exacerbation of and
      coping with IBD. The psychosocial consequences of the illness become more
      significant with increasing severity of the disease. Therefore integrated
      psychosomatic care should be provided, the patient's psychosocial status and the
      demand for additional psychological care should be assessed and offered, if
      indicated.

PMID- 16790163
TI  - [Effects of psychotherapeutic interventions on length of stay in cardiology
      inpatients].
AB  - OBJECTIVES: Mental comorbidities as recorded in the DRG system by the Patient
      Comorbidity and Complication Level (PCCL) cause extended length of stay in
      cardiology with resultant higher costs. Studies analyzing the influence of a
      psychiatric consultation and liaison service on the length of stay and the costs
      incurred thereby have generated inconsistent results. The present prospective
      study examines the effects of the psychotherapeutic liaison service on the length
      of stay. METHODS: In the course of 6 months, two cardiology wards were
      alternately provided traditional psychotherapeutic consultation and
      psychotherapeutic liaison service based on a Cross-Over-Design (A-B-A). Inclusion
      criteria for patients was the presence of one of the four most common
      cardiological diagnoses (ischemic heart diseases, heart valve defects,
      cardiomyopathies, arrhythmias). After the exclusion of patients with a length of
      less than five days, the random sampling comprised n = 317 patients. RESULTS: The
      study showed no direct correlation between the intensified care system of the
      liaison service and a reduction in the length of stay. The results obtained
      remained consistent even after controlling for age, sex, and case complexity.
      Recommendations for further investigations are discussed.

PMID- 16790164
TI  - [Implementation of the multi-center basis documentation CL-BaDo for conciliar and
      liaison services: generating data for internal quality management and cost
      calculation].
AB  - In the German DRG system the funding of CL services is not ensured. The
      documentation of psychiatric comorbidity and CL care delivery is a pre-condition
      to the development of funding models for CL-services. A task force of several
      German psychosomatic associations (German College of Psychosomatic Medicine,
      German Society of Psychosomatic Medicine and Psychotherapy, General Medical
      Society for Psychotherapy) developed a new documentation form for CL-services (CL
      BaDo). The pilot study explored the multicenter implementation of CL-BaDo and the
      use of the documentation form for quality management and cost calculation. Over a
      period of at least three months, participating CL-services documented all CL
      cases consecutively with the CL-BaDo. One site applied full electronic data
      processing. 2116 CL cases from eight psychosomatic CL-services were analysed. The
      CL-BaDo is a time-efficient, feasible and acceptable documentation form for CL
      service delivery. The full electronic data processing enables networking with a
      hospital information system to produce higher data quality. The data of CL-BaDo
      can be used locally for quality management, development of management strategies
      and communication with consultants, as well as nationwide for health policy
      questions and research.

PMID- 16790165
TI  - [Treatment of depression: what do women need?].
AB  - OBJECTIVES: To answer the question of adequate treatment of depression in women
      from a scientific point of view, it is necessary to investigate the aetiology of
      depressive disorders as they relate to bio-genetic, mental and social factors.
      METHODS: For a comprehensive understanding of depressive disorders in women three
      factors are analysed: (1) the severity of a depression, (2) the phenomenological
      description, and (3) the factors of the development of depression in the female
      life cycle. RESULTS: Different treatment strategies for women can be developed on
      the basis of these phenomenological and psychodynamic considerations. A case
      study of a female patient suffering from depressive adjustment disorder who had a
      background history of sexual reproductive problems is presented to demonstrate
      characteristic factors in women which may serve as indicators for psychoanalytic
      focal psychotherapy. DISCUSSION: In our opinion, psychoanalytic theory in its
      complexity, working with unconscious phantasies, fears concerning body integrity
      and relationships to others, is the most appropriate method to determine specific
      factors behind the pathogenesis and the persistence of depressive disorders in
      women.

PMID- 16790166
TI  - [Which core conflictual relationship themes are consistent with depressive
      symptoms? An exploratory study].
AB  - OBJECTIVES: We study the pattern of interpersonal alliances typical of depressive
      symptoms by means of the Core Conflictual Relationship Theme (CCRT) method. In an
      exploratory manner we examine which CCRT-coded wishes, perceived responses from
      the other and associated responses of the self predict the magnitude of a score
      on the Beck Depression Inventory-II. METHODS: Interview data from 31 mental
      health patients were coded (CCRT expanded standard categories system). Relations
      between the CCRT categories and the dependent variable were examined by combining
      1000-fold forward stepwise regression analyses, and multiple regression analyses
      in which confidence intervals were estimated with the bootstrap technique.
      RESULTS: Three CCRT categories that jointly explain more than half of the
      variance were selected: diminished levels of the wish to be understood, and
      elevated levels of disliking others and of feeling helpless. CONCLUSIONS: The
      results and implications for psychotherapy are discussed within a psychoanalytic
      context. Suggestions for further research are indicated.

PMID- 16790167
TI  - [Comparison of inpatient and day clinic treatment of anorexia nervosa].
AB  - OBJECTIVES: Explorative comparison of short term outcomes of day clinic and
      inpatient treatment for anorexia nervosa. METHODS: N = 13 consecutively admitted
      day clinic patients (anorexia nervosa; DSM IV) were matched with N = 13
      inpatients (variables: age, duration of illness, gender, admission weight,
      subtype of anorexia nervosa). Results at discharge were compared using defined
      outcome criteria as well as scores of the SCL-90-R and EDI-2. RESULTS: After
      inpatient treatment significantly more patients showed a good outcome (predefined
      criteria). Effect sizes also pointed to a superiority of inpatient treatment.
      CONCLUSIONS: In the initial phase of therapy the structured and holding
      environment of an inpatient unit may be favourable for severely underweight
      anorexic patients. The interpretation of these results is limited due to the
      small sample size.

PMID- 16790168
TI  - [14th Congress of the German Society of Psychosomatic Medicine and Medical
      Psychotherapy: "Psychosomatic thinking--psychosomatic management"].

PMID- 16790170
TI  - EU Directive, ICNIRP guidelines and Polish legislation on electromagnetic fields.
AB  - This review describes the general provisions of and the philosophy behind
      European Directive 2004/40/EC and ICNIRP (International Commission on Non
      Ionizing Radiation Protection) guidelines. As an example of national legislation
      on the protection of workers against excessive electromagnetic field exposure,
      regulations established in Poland are summarized. The problems of a practical
      implementation of the Directive's provisions are discussed.

PMID- 16790171
TI  - Electromagnetic fields in offices.
AB  - With the increased use of electric and electronic equipment in our offices, our
      daily exposure to electromagnetic fields has become increasingly complex due to
      the great variety of the frequency content of the fields. Today focus has shifted
      from monitors as the dominating sources of electromagnetic fields to other
      electronic equipment, cabling, nearby substations, power lines and stray currents
      in buildings. In the last 5 years wireless communication has become common in our
      offices. These devices use radio frequency waves to communicate and are therefore
      sources of radio frequency fields in our offices. To a certain degree, they all
      add to the complicated issue of the extensive field frequencies found in offices.
      The exposure of office workers is generally considered to be low and not in
      conflict with the existing guidelines, but if a precaution approach is applied
      there are a number of measures that can be taken to reduce the electromagnetic
      fields in offices in order to obtain a good electrical environment.

PMID- 16790172
TI  - Occupational exposure to power frequency fields in some electrical transformation
      stations in Romania.
AB  - The aim of this study is to investigate the levels of electric and magnetic power
      frequency fields at 8 electrical transformation stations in the North-East
      counties of Romania and to check their compliance with standards. Spot
      measurements were carried out on both electric and magnetic fields under overhead
      conductors of 110-, 220- and 380-kV installations. The magnetic field levels were
      several orders of magnitude below the reference level for occupational exposure
      set by ICNIRP (International Commission on Non-Ionizing Radiation) or by Romanian
      regulations. In contrast, the electric field levels were about the same order of
      magnitude as the reference levels. In 2 electrical stations the reference level
      of 10 kV/m was exceeded at specific locations within the outdoor installations
      area. However, the additional reference level for short-time exposure included in
      Romanian regulations, 30 kV/m, was not exceeded.

PMID- 16790173
TI  - Health risk assessment of occupational exposure to a magnetic field from magnetic
      resonance imaging devices.
AB  - Health care staff who operate magnetic resonance imaging (MRI) devices are
      exposed to a static magnetic field of significant spatial heterogenity always
      produced by MRI magnets during the whole shift. They can also be exposed to
      pulses of a time-varying magnetic field (gradient field) present only during
      patients' examinations. The level of the workers' exposure depends both on the
      type of the magnet and on the ergonomic design of each MRI device. The paper
      presents methods used for measuring and assessing workers' exposure. It also
      discusses the results of inspection measurements carried out next to
      approximately 20 MRI devices of approximately 0.2-2.0 T. The presented
      characteristic and overview of the variability of workers' exposure to a variety
      of MRI devices supports the need for data on monitoring occupational exposure to
      MRI. International exposure assessment standards and guidelines (International
      Commission on Non-Ionizing Radiation Protection [ICNIRP], Institute of Electrical
      and Electronics Engineers [IEEE], American Conference of Governmental and
      Industrial Hygienists [ACGIH], European Commission directive), and those
      established in Poland are also compared.

PMID- 16790174
TI  - Magnetic fields of induction heaters in the framework of directive 2004/40/EC of
      the European Parliament and of the Council.
AB  - The spectrum and the polarization of the magnetic flux density (B-field) of 6
      induction heaters and 1 arc oven were measured by means of a PMM (Italy) spectrum
      analyser. The spectrum analysis showed that no substantial harmonics were
      observed while the polarization analysis revealed that the operator's exposure
      was non-homogeneous within a distance of 1.5 m from the heater. When the distance
      was larger, the body was homogeneously exposed. In general we can state that the
      B-field strongly varied between heaters and that exposure exceeded the
      occupational reference levels recommended by the International Commission on Non
      Ionizing Radiation Protection (ICNIRP) (1998) and European Directive 2004/40/EC
      in 5 of the 7 heaters. Within the framework of the Directive some protection
      actions should be taken. Whereas mitigation of existing/old induction ovens is
      difficult, the design of new induction heaters and their housing should be based,
      among others, on electromagnetic reducing engineering concepts.

PMID- 16790175
TI  - Application of EMF emission measurement techniques to wireless communications
      systems for compliance with directive 2004/40/EC.
AB  - Europe is the only region in the world with common legislative acts regulating
      exposure to electromagnetic fields (EMF) for both the general public and workers.
      Council Recommendation 1999/519/EC deals with the limitation of exposure of the
      general public to EMF (0 Hz-300 GHz). Directive 2004/40/EC regulates the minimum
      health and safety requirements regarding the exposure of workers to the risks
      arising from EMF. This paper discusses the general application of existing
      standards and recommendations in measurement techniques for determining
      compliance of measured exposure limit values and action values with those defined
      in 2004/40/EC.

PMID- 16790176
TI  - Occupational exposure to base stations-compliance with EU directive 2004/40/EC.
AB  - The rapid growth of mobile communications has not only led to a rising number of
      mobile telephones. It has also made base stations essential for these services
      widespread on many roofs. However, not everyone is aware that working close to
      sources of high frequency electromagnetic fields (EMF), such as transmitter
      antennas for mobile phones, pagers and police, fire and other emergency services,
      can result in high EMF exposure. This paper deals with measurements and
      calculations of the compliance boundary for workers in one typical roof top base
      station setting according to EU Directive and other relevant EN standards.

PMID- 16790177
TI  - Electromagnetic fields: principles of exposure mitigation.
AB  - Basic principles of reducing exposure to electromagnetic fields are reviewed in
      this article. Measures to reduce exposure can be divided into
      organisational/administrative and technical/engineering actions. Both strategies
      are briefly analysed and the basic principles of the theory of shielding are
      presented. A definition of shielding effectiveness (SE) is given, and the results
      from the general Transmission Lines Theory are presented. Practical situations of
      shielding static and time-varying electric and magnetic fields are discussed on
      the basis of the physical properties of the fields and of the shield.

PMID- 16790178
TI  - Quasi-static electromagnetic dosimetry: from basic principles to examples of
      applications.
AB  - An overview of quasi-static electromagnetic dosimetry is presented. After an
      introductive description of quantities and standards and a quick look at
      experimental and analytical approaches, attention is focused on numerical
      dosimetry. The process that leads to the calculation of results is analyzed in
      its basic steps, including the representation of the human body by means of a
      realistic voxel phantom. The most popular numerical methods are then described.
      An analysis of different methods in the same framework emphasizes common features
      and differences. This can help in choosing a more suitable method to solve a
      particular problem. An example of an application is finally reported.

PMID- 16790179
TI  - [Secondary prophylaxis with elastic band ligation in esophageal-gastric varices].
AB  - The aim of the present study was to determine the usefulness of elastic band
      ligation in the prevention of hemorrhage recurrence due to esophageal-gastric
      varices. Sixty-five patients who survived an episode of variceal hemorrhage were
      included in the study. Twenty-nine patients (45%) were Child-Pugh class A, 25
      (38%) were class B, and 11 (17%) were class C. The cause of cirrhosis was
      hepatitis C virus and alcohol in 45% and 31% of the patients, respectively. The
      first ligation session was performed between the third and fifth day after the
      hemorrhagic episode and subsequent sessions were carried out at intervals of 3-4
      weeks. The ligation sessions were performed with antibiotic prophylaxis. A mean
      of 2.7 bands were placed per session (range 1-5), and the mean number of sessions
      required per patient to achieve variceal eradication was 2.5 (range 1-6). The
      rate of bleeding recurrence was 24.6% (16 episodes). In conclusion, endoscopic
      elastic band ligation is a useful technique for the eradication of esophageal
      varices and for the prevention of bleeding recurrence.

PMID- 16790180
TI  - [Tacrolimus in the treatment of refractory moderate-to-severe inflammatory bowel
      disease].
AB  - INTRODUCTION: The primary endpoint of this study was to evaluate the efficacy of
      oral tacrolimus in patients with active moderate-to-severe luminal IBD, mainly
      those refractory to steroids. Secondary endpoints were surgery requirements
      during follow-up, the percentage of patients achieving steroid withdrawal, and
      treatment safety. PATIENTS AND METHOD: Nineteen patients were included. The main
      indication for tacrolimus therapy was steroid resistance. The mean duration of
      treatment was 11 (range 3- 13) and 15 (range 4-44) months in patients with UC and
      CD, respectively. Remission was evaluated at weeks 4, 8 and 24 from the start of
      treatment, using the Harvey-Bradshaw index and the Truelove-Witts criteria for CD
      and UC patients, respectively, and acute- phase reactants (Serum erythrocyte
      sedimentation rate and C-reactive protein). Steroid withdrawal, need for surgery,
      and previous and concomitant medication were also evaluated. RESULTS: Overall,
      47%, 66% and 41% of the patients were in complete remission at weeks 4, 8 and 24,
      respectively. Steroid withdrawal was achieved in 50% of the patients. Among
      patients who could not undergo complete steroid withdrawal, steroid therapy was
      reduced to a mean prednisone dose of 12.5 mg /day (range 10-15 mg). Surgery was
      required in 16% (mean follow-up of 38 months). Adverse effects occurred in 63%
      patients, who improved with dose reduction; none of the patients required
      tacrolimus withdrawal. CONCLUSIONS: Oral tacrolimus could be a safe, effective
      and useful option in patients with refractory IBD.

PMID- 16790181
TI  - [Liver damage in workers exposed to hydrocarbons].
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the
      occurrence of hypertransaminasemia (hTAMSemia) as an indicator of liver damage
      and to establish the association of this hepatotoxicity with exposure to aromatic
      hydrocarbons (benzene, toluene, and xylene [BTX]) among workers in a
      petrochemical company. PATIENTS AND METHOD: The medical records of 167 industrial
      employees, 95 with hydrocarbon exposure (EHCs) and 72 without exposure (NEHCs)
      were reviewed. Age, sex, number of years employed, body mass index, and
      biochemical and hematological parameters were evaluated. Employees with previous
      liver disease, diabetes mellitus, or alcohol intake (> 50 g/day) were excluded.
      In employees with hTAMSemia, we performed a proteinogram and hepatic
      ultrasonography and tested blood samples for prothrombin and hepatitis B and C
      markers. Within this subgroup, 3 workers were excluded (due to serum markers of
      hepatitis B virus in 2 and refusal to participate in 1), leaving a total of 92 in
      the EHC group. Finally, the working environment was screened for volatile
      contaminants. RESULTS: Twenty-seven employees from the EHC group (29.4%) and 1
      from the NEHC group (1.4%) had hTAMSemia (p = 0.001). The remaining biochemical
      tests and parameters measured showed no significant differences between the two
      groups. Comparison between the EHC subgroup of 27 workers showing hTAMSemia and
      the remainder of the EHC group with normal values (65 workers) revealed no
      differences in the other parameters measured. Of the 27 workers of the former
      subgroup, 14 (51.9%) showed ultrasonographic images compatible with a fatty
      liver. One worker (1.4%) in the NEHC group showed hTAMSemia and ultrasonography
      compatible with fatty liver. The environmental levels of BTX during the 9 months
      of the study remained below the maximum values permitted by law in Argentina
      (benzene, 1.5 ppm., toluene 10 ppm and xylene 18.5 ppm). The odds ratio of
      developing hTAMSemia in the EHC group was 27.7 (p = 0.002). CONCLUSIONS:
      Occupational exposure to aromatic hydrocarbons may cause liver damage. The liver
      is more vulnerable to these hydrocarbons than bone marrow. These conclusions
      would argue for a modification of the environmental regulations currently in
      force within the petroleum refineries in Argentina.

PMID- 16790182
TI  - [Upper digestive hemorrhage due to aortoesophageal fistula].
AB  - We describe the case of a 60-year-old woman who presented with thoracic pain
      followed by hematemesis. Aortoesophageal fistula was diagnosed. Double aortic and
      esophageal protheses were placed with good clinical outcome. After 15 days, the
      patient presented migration of the esophageal prothesis and a further endoscopic
      examination was performed. A fishbone was visualized in the fistula orifice.

PMID- 16790183
TI  - [Malabsorption syndrome due to Strongyloides stercoralis associated with Loeffler
      syndrome in a 29-year-old woman].
AB  - We report a case of chronic infection by Strongyloides stercoralis in a 29-year
      old Colombian woman who had been living in Spain for 2 years. The patient had
      recurrent abdominal pain and malabsorption syndrome. The diagnosis was made
      through intestinal biopsy in upper gastrointestinal endoscopy. Transport of the
      parasite through the lung parenchyma (Loeffler syndrome) was visible on simple
      chest X-ray. Bronchoalveolar lavage, bronchoalveolar aspirate and repeated stool
      examination were negative.

PMID- 16790184
TI  - [Cystic dystrophy of the duodenal wall. An underdiagnosed complication in
      aberrant pancreas].
AB  - Cystic dystrophy of the duodenal wall is an uncommon complication of aberrant
      pancreas characterized by increased duodenal wall thickness associated with
      intraparietal cystic lesions. We present the case of a male patient with cystic
      dystrophy of the duodenal wall, which posed major diagnostic problems due to the
      difficulty of distinguishing this entity from tumors of the head of the pancreas.
      Echoendoscopy was useful in establishing the definitive diagnosis, allowing
      puncture-evacuation of the intracystic contents with resolution of obstructive
      symptoms.

PMID- 16790185
TI  - [Unmet needs in the approach to irritable bowel syndrome].

PMID- 16790186
TI  - [Eosinophilic granulocytes: from common residents in normal gastrointestinal
      mucosa to aggressive agents of eosinophilic gastroenteritis].
AB  - Because of their biological affinity for normal gastrointestinal (GI) mucosa,
      eosinophilic granulocytes are "normal residents" in the mucosa. This
      physiological GI eosinophilia translates into a state of "permanent normal
      inflammation", which means that the mucosa's local immune system is constantly
      confronted by dietary proteins and indigenous microorganisms. This eosinophilic
      infiltration of the GI mucosa is increased, reactively, in the course of local
      inflammatory processes, collagenosis, infections (especially helminthic
      infections), vasculitis, neoplasms and IgE-dependent allergic reactions to food.
      Lastly, GI eosinophilia that is clearly aggressive, both because of its intensity
      and its persistence, is what characterizes eosinophilic gastroenteritis. In the
      present article, we summarize the ethiopathogenic and clinico-epidemiological
      features of this process, as well as its position within the field of
      immunopathologic food intolerance.

PMID- 16790187
TI  - [New pathogenic concepts in hereditary hemochromatosis].

PMID- 16790188
TI  - [Alternative sources of hepatocytes for cell therapy].
AB  - There is an urgent need to search for alternatives to whole organ
      transplantation. Several methods have been proposed. Among these strategies, cell
      transplantation is currently one of the most promising. To achieve this aim, in
      addition to highly differentiated adult hepatocytes, the use of stem cells is
      considered a highly attractive therapeutic method for the treatment of liver
      disease and for temporary support of hepatic function until a liver becomes
      available for organ transplantation. This strategy is based on the ability of
      stem cells to differentiate into different cellular types according to their
      environment. Therefore, stem cells could be an unlimited source of hepatic cells
      for transplantation and gene therapy. Bone marrow is considered the most
      promising source of adult stem cells, partly due to the versatility of the cells
      obtained in repairing damaged tissues of several lineages. Several different
      types of stem cells have been described in bone marrow: hematopoietic,
      mesenchymal, side population and multipotent adult stem cells. Bone marrow cells
      have been hypothesized as a third recruitment source in liver regeneration in
      addition to hepatocytes and endogenous liver stem cells. Consequently, attempts
      have been made to differentiate them into hepatic lineage for their subsequent
      use in hepatic cell therapy. The present article reviews the progress made in
      this field or research.

PMID- 16790189
TI  - [Proximal migration of a distal common bile duct prosthesis to the left hepatic
      duct].

PMID- 16790190
TI  - [Importance of magnetic resonance imaging in the diagnosis of multiple small
      biliary hamartomas (von Meyenburg complexes)].

PMID- 16790191
TI  - [Ileocolonic invagination due to an inflammatory fibroid polyp in a senile
      patient. Endoscopic diagnosis].

PMID- 16790192
TI  - [Upper digestive hemorrhage as the first manifestation of acinar cell carcinoma
      of the pancreas].

PMID- 16790193
TI  - [Prevention of sudden death with the implantable defibrillator in hypertrophic
      cardiomyopathy].

PMID- 16790194
TI  - [Stress echocardiography in patients with acute myocardial infarction. What is
      the extent of coronary artery disease and how should it be evaluated?].

PMID- 16790195
TI  - [His-bundle pacing: great concept, difficult in practice].

PMID- 16790196
TI  - [The implantable cardioverter-defibrillator and hypertrophic cardiomyopathy.
      Experience at three centers].
AB  - INTRODUCTION AND OBJECTIVES: Although implantable cardioverter-defibrillators
      (ICDs) are recommended for high-risk patients with hypertrophic cardiomyopathy
      (HCM), there is no agreement on their general use. Moreover, little information
      is available on ICD use in this setting in Spain. Our aims were to describe the
      characteristics of HCM patients who received ICDs at three hospitals in Spain,
      and to study indications for device implantation and the results of follow-up in
      device users. METHODS: We evaluated risk factors for sudden death in HCM patients
      with ICDs, including family history of sudden death, recurrent syncope, maximum
      wall thickness > or =30 mm, left ventricular outflow pressure gradient >30 mmHg,
      abnormal blood pressure response to exercise, and nonsustained ventricular
      tachycardia. During regular follow-up, appropriate and inappropriate
      administration of ICD therapy was recorded. RESULTS: Of 726 HCM patients, 45
      (6.2%) had an ICD (mean age 43 [20] years). The proportion of patients with ICDs
      at the three centers studied was highly variable despite patients' clinical
      characteristics being similar. The indication for implantation was primary
      prevention in 27 patients and secondary prevention in 18. During follow-up
      (median 32 months), ICD therapy was administered appropriately in 10 (22.0%)
      patients (in nine, as secondary prevention and, in one, as primary prevention).
      The annual appropriate ICD therapy rate was 11.1% for secondary prevention and
      1.6% for primary prevention. Two patients received an ICD to treat ventricular
      fibrillation and eight, to treat sustained ventricular tachycardia. The only
      significant predictor of appropriate ICD therapy was a history of sustained
      ventricular tachycardia or ventricular fibrillation (hazard ratio =13.3, P=.014).
      CONCLUSIONS: The percentage of HCM patients undergoing ICD implantation at
      Spanish hospitals was highly variable, possibly due to different selection
      criteria. When used as secondary prevention, ICD therapy was administered
      appropriately in a high proportion of cases (50% in 3 years).

PMID- 16790197
TI  - [Stress echocardiography in the identification of left anterior descending
      coronary artery disease in patients with inferior myocardial infarction and a
      positive exercise electrocardiography result].
AB  - INTRODUCTION AND OBJECTIVES: In patients with an inferior myocardial infarction
      (IMI), ST-segment depression in left precordial leads during exercise
      electrocardiography (ExECG) has been associated with left anterior descending
      coronary artery (LADCA) disease. The aim of this study was to assess the value of
      stress echocardiography in identifying LADCA disease in patients with IMI and a
      highly abnormal ExECG result. METHODS: The study included patients with an IMI
      and an abnormal ExECG result whose coronary angiography findings were available.
      A highly abnormal ExECG result was defined as ST-segment depression in three or
      more leads, including V5. The wall motion score index was calculated and each
      patient was evaluated echocardiographically for ischemia in LADCA territory.
      RESULTS: Of 241 patients who underwent stress ECG, 100 (mean age 57 [11] years)
      met inclusion criteria. Some 38 had significant LADCA stenosis and, in 75, ExECG
      gave a highly abnormal result. The sensitivity, specificity and accuracy of a
      highly abnormal ExECG result for detecting LADCA disease were 74% (60%-88%), 26%
      (15%-37%), and 44% (34%-54%), respectively. Echocardiographic detection of
      ischemia had similar sensitivity, at 74%, but higher specificity, at 92% (P<
      .001), and accuracy, at 85% (P< .001). Multivariate analysis of clinical,
      exercise test, and stress echocardiography variables revealed that the only
      independent predictors of LADCA disease were age (OR=1.070), recent IMI
      (OR=0.136), and ischemia in LADCA territory (OR=19.9). CONCLUSIONS: Stress
      echocardiography is a good noninvasive technique for detecting LADCA disease in
      patients with an IMI. The diagnostic accuracy of a highly abnormal ExECG result
      is not sufficient for its use in this clinical setting.

PMID- 16790198
TI  - [Permanent His-bundle pacing in patients with infra-Hisian atrioventricular
      block].
AB  - INTRODUCTION AND OBJECTIVES: Permanent His-bundle pacing is effective in patients
      with supra-Hisian atrioventricular block. We report our experience in patients
      with infra-Hisian atrioventricular block. METHODS: The study involved selected
      patients referred for syncope and intraventricular conduction disturbance, infra
      Hisian atrioventricular block, with left ventricular dyssynchrony and no coronary
      sinus access. All patients underwent electrophysiological study to evaluate infra
      Hisian atrioventricular conduction, both at baseline and after flecainide
      administration. We selected patients with an indication for permanent pacing in
      whom His-bundle pacing produced a narrow QRS complex. Leads were implanted in the
      right atrium, in the bundle of His, and at the apex of the right ventricle, and
      connected to the atrial, left ventricular, and right ventricular terminals,
      respectively, of a biventricular pacemaker generator. All pacemakers were
      programmed in DDD mode with a left ventricle-right ventricle interval of 80 ms.
      RESULTS: Between February and December 2004, seven patients met the study's
      inclusion criteria. The His-bundle lead was implanted successfully in five. The
      His-bundle pacing threshold remained stable in two patients, whereas it increased
      in three. During follow-up, at between 2 and 12 months, no lead dislodgement or
      failure to capture was observed. Echocardiography did not disclose any
      deterioration in ventricular function, or any worsening of or new valvular
      incompetence, but showed that ventricular dyssynchrony had disappeared in
      previously affected patients. CONCLUSIONS: His-bundle pacing is the only pacing
      mode capable of inducing a physiologically normal ventricular contraction. It can
      be used in some patients with infra-Hisian atrioventricular block.

PMID- 16790199
TI  - [Inducibility of atrial arrhythmias after adenosine and isoproterenol infusion in
      patients referred for atrial fibrillation ablation].
AB  - INTRODUCTION AND OBJECTIVES: The identification and ablation of atrial ectopic
      foci could complement the conventional empirical pulmonary vein approach and may
      increase the success rate of atrial fibrillation ablation. Although both
      adenosine and isoproterenol infusion have been reported to induce ectopics, no
      clear findings on their use during ablation have been published. Our aim was to
      investigate the utility of these two pharmacologic maneuvers in patients referred
      for atrial fibrillation ablation. METHODS: The effects of adenosine infusion,
      isoproterenol infusion, or both were evaluated in 53 patients with refractory
      atrial fibrillation referred for ablation. Patients were in sinus rhythm during
      evaluation. RESULTS: Administration of adenosine or isoproterenol induced atrial
      arrhythmias in 46 patients (87%). Arrhythmia inducibility was similar in those
      with paroxysmal and those with persistent atrial fibrillation (87% and 86%,
      respectively). Atrial ectopics alone were induced in 31 patients (65%), atrial
      tachycardia in four (8%), and atrial fibrillation in 13 (27%). In 10 patients
      (19%), ectopic foci were located outside the pulmonary veins and subsequently
      underwent ablation. In 32 of the 46 patients with inducible arrhythmias, only the
      induced ectopic foci were ablated (mean 1.4 [0.6] targets per patient). The long
      term success rate of first procedures was 66%. CONCLUSION: Adenosine and
      isoproterenol infusion induced atrial ectopics in most patients with drug
      refractory atrial fibrillation while they were in sinus rhythm. In almost 20%,
      the ectopic foci were located outside the pulmonary veins. The effectiveness of
      induced ectopic-guided ablation observed in our patient series supports the
      clinical utility of this approach.

PMID- 16790200
TI  - [Does intracoronary abciximab improve the outcome of percutaneous coronary
      interventions? A randomized controlled trial].
AB  - INTRODUCTION AND OBJECTIVES: It has been clearly demonstrated that abciximab is
      useful in percutaneous coronary interventions. However, it is not known if
      intracoronary administration of the initial abciximab bolus improves outcome.
      Moreover, there may be safety concerns. METHODS: The study was a single-center
      prospective randomized trial that included all patients undergoing coronary
      angioplasty involving the use of abciximab. Patients were randomized to either
      intracoronary or intravenous administration of the abciximab bolus. The primary
      endpoint was the incidence of major adverse cardiac events (i.e., death,
      myocardial infarction, or the need for revascularization); secondary endpoints
      were hemorrhagic complications and the troponin-I level. RESULTS: The study
      included 137 patients; 72 received an intracoronary abciximab bolus and 65, an
      intravenous bolus. Clinical characteristics and baseline angiographic findings
      were similar in the two groups. All patients underwent coronary stent
      implantation. No difference was observed between the intracoronary bolus group
      and the intravenous bolus group in type of stent used (drug eluting stent 47.2%
      vs 50.8%, respectively), total stent length, or final TIMI flow grade (3 vs 2.97,
      respectively). The intervention success rates were also similar (98.5% vs. 99%,
      respectively). No complication associated with the administration route was
      reported. However, the level of the myocardial injury marker troponin I increased
      significantly in the intravenous bolus group. Clinical follow-up at 1 year did
      not reveal any difference in the incidence of major adverse cardiac events: 8.5%
      in the intracoronary bolus group versus 6.2% in the intravenous bolus group.
      CONCLUSIONS: Intracoronary administration of an abciximab bolus did not appear to
      be less safe or effective than intravenous administration. Less post-procedural
      myocardial damage was observed in the intracoronary bolus group.

PMID- 16790201
TI  - [Limitations of myocardial blush grade in the evaluation of myocardial perfusion
      in patients with acute myocardial infarction and TIMI grade 3 flow].
AB  - INTRODUCTION AND OBJECTIVES: An analysis was made of variability in the
      measurement of the angiographic index blush between a university hospital and an
      independent core laboratory, as well as its correlation with perfusion analyzed
      by intracoronary myocardial contrast echocardiography (MCE) and the ventricular
      function at the sixth month. METHODS: The study comprised 40 patients with a
      first ST-segment elevation myocardial infarction, single-vessel disease and open
      infarct-related artery. Perfusion was quantified by angiography (median fifth
      day, range 3-7) with blush in our laboratory and in an independent core
      laboratory. MCE was performed. Ejection fraction at the sixth month was
      determined with magnetic resonance imaging. RESULTS: We found a weak correlation
      (r=0.38) between both laboratories. In the comparison of blush measurements
      concordance was 80%, kappa=0.43 if normality was defined by blush 2-3; and
      concordance 55%, kappa=0.1 for blush 3. Neither perfusion analyzed by MCE (r=
      0.23, P=.2) nor ejection fraction by resonance (r=0.20, P=.3) did correlate to
      blush. CONCLUSIONS: After infarction in patients with TIMI 3, variability is
      observed in blush measurements between a university hospital and an independent
      core laboratory, therefore it seems advisable to centralize blush measures in
      highly specialized core laboratories. A weak correlation was detected with
      perfusion analyzed by MCE and with late systolic function.

PMID- 16790202
TI  - [Coronary angiography: beyond coronary anatomy].
AB  - Although technical advances enable normal epicardial coronary artery blood flow
      to be restored in most patients suffering myocardial infarction, restoration of
      blood flow is not always followed by improved myocardial perfusion. Recently,
      therefore, interest in the assessment of myocardial perfusion has grown, and a
      number of different assessment methods are available. The aim of this article was
      to provide an evaluation of the additional information that can be obtained from
      the widely used technique of conventional coronary angiography. We present a
      review of the data on epicardial coronary artery blood flow (both
      semiquantitative and quantitative) and on microvascular blood flow that can be
      obtained using coronary angiography and discuss their prognostic significance.

PMID- 16790203
TI  - [Cardiac arrhythmias in women].
AB  - The aim of this study was to review published data on gender differences in
      cardiac electrophysiology and in the presentation and clinical treatment of
      arrhythmias. The evidence from studies published to date show that women have a
      higher mean resting heart rate, a longer QT interval, a shorter QRS duration, and
      a lower QRS voltage than men. Women have a higher prevalence of sick sinus
      syndrome, inappropriate sinus tachycardia, atrioventricular nodal reentry
      tachycardia, idiopathic right ventricular tachycardia, and arrhythmic events in
      the long-QT syndrome. In contrast, men have a higher prevalence of
      atrioventricular block, carotid sinus syndrome, atrial fibrillation,
      supraventricular tachycardia due to accessory pathways, Wolff-Parkinson-White
      syndrome, reentrant ventricular tachycardia, ventricular fibrillation and sudden
      death, and the Brugada syndrome. With regard to implantable devices, it has been
      reported that defibrillators offer similar benefits in men and women. Moreover,
      there is no gender difference in the percentage who respond well to
      resynchronization therapy: survival is similar in the two sexes. However, it
      should be noted that few women have participated in studies of all types of
      therapy, including catheter ablation, resynchronization therapy, and the use of
      implantable defibrillators.

PMID- 16790204
TI  - [Intravascular ultrasound-guided percutaneous treatment in a case of spontaneous
      coronary artery dissection].

PMID- 16790205
TI  - [Anomalous coronary arteries originating in the contralateral sinus of Valsalva:
      registry of thirteen Spanish hospitals (RACES)].
AB  - The registry contains information collected during 2003 from thirteen Spanish
      hospitals on the incidence, clinical presentation, initial course, diagnostic
      imaging, and treatment of anomalous coronary arteries originating in the
      contralateral coronary sinus. In a total of 23,300 coronary angiograms, 98
      anomalous coronary arteries were detected (incidence 0.4%): 46 circumflex
      coronary arteries (47%), 25 right coronary arteries (25.5%), 10 left main
      coronary arteries (10.2%), three left anterior descending arteries (3.1%), six
      single coronary arteries (6.1%), and eight other anomalies (8.2%). The most
      frequent indication for angiography was angina (43.9%). The initial course of the
      anomalous coronary artery was not identified in 40.8% of cases. In two patients
      (2%), diagnostic imaging was used to identify the initial course. Associated
      atherosclerotic disease was present in 51% of patients. In addition, 18.4% had
      associated valvular disease, with the aortic valve being affected most often
      (15.2%). Some 16.3% of patients underwent treatment for the coronary anomaly. The
      incidence was similar to that observed in other published series, with anomalies
      in the circumflex coronary artery being diagnosed most frequently. Diagnostic
      imaging was underused.

PMID- 16790206
TI  - [Comparison between theoretical an actual intracoronary stent dimensions in non
      complex lesions].
AB  - The minimum in-stent lumen diameter is a predictor of restenosis. Stent
      dimensions provided by manufacturers are derived from in vitro tests. The aim of
      this study was to compare actual stent dimensions obtained by angiography and
      intracoronary ultrasound with dimensions that would be expected theoretically for
      a given inflation pressure in a cohort of 100 non-complex lesions suitable for
      direct stenting. Significant differences were found between the theoretical
      diameters and those observed by angiography and ultrasound. The actual-to
      theoretical diameter ratio was 0.83 (0.09) when measured using angiography and
      0.78 (0.10), using intravascular ultrasound. In lesions without severe
      calcification, stent dimensions were significantly smaller than indicated by the
      manufacturer. Nominal figures should not be used as reference values for stent
      implantation.

PMID- 16790208
TI  - [Takotsubo syndrome with coronary lesions].

PMID- 16790207
TI  - [Association of coronary risk factors in old age. AFRICA study].
AB  - We carried out a multicenter cross-sectional study in Argentina to investigate
      the prevalence of behavioral and other risk factors for coronary heart disease in
      patients aged 90 years or more and to study the association between risk factors
      and longevity. Data were collected on 322 individuals aged 90 years or more, 47%
      of whom had a family history of longevity. The majority ate meals comprising
      mainly fruit, milk and vegetables every day and half of the participants drank a
      moderate amount of red wine. On average, their body mass index was normal and
      they regularly took some form of physical activity. Generally, diabetes mellitus
      was associated with obesity. The onset of arterial hypertension occurred at the
      high average age of 72 years. Few were found to be current smokers. Few
      individuals had two concurrent risk factors, and even fewer had three concurrent
      major coronary risk factors. In conclusion, patients aged 90 or more in our
      series showed characteristics indicating both a genetic trait and environmental
      factors favouring longevity.

PMID- 16790209
TI  - [Left main total occlusion treated with drug eluting stent].

PMID- 16790210
TI  - [Vasco de Gama movement--the new European generation of family doctors].

PMID- 16790211
TI  - [Effectiveness of the new antidepressants compared with classic serotonin uptake
      inhibitors].

PMID- 16790212
TI  - [Physician/patient relationship in diabetes mellitus type 1 treatment. A
      qualitative study].
AB  - OBJECTIVES: To know the experiences and expectations of diabetes mellitus type 1
      (DM1) patients and their relatives as regards the relationships established with
      doctors, and the impact of such relationships on their strategies to cope with
      the disease and treatment. DESIGN: Qualitative design based on focus groups
      conducted in 2001. LOCATION: Several health care centres in Granada and Seville,
      Spain. PARTICIPANTS: DM1 patients and their relatives and/or carers. METHOD:
      Theory-based sampling including the most representative profiles. Qualitative
      analysis procedure: text coding, triangulation and interpretation of results.
      RESULTS: Doctor/patient relationship highly influences the emotional experience
      of disease and the way patients gain control over it. Interviewed patients said
      that the relationship with doctors is focused on disease signs and symptoms,
      leaving emotional aspects aside. Very often, provider communication is built on
      recrimination and threat. Treatment is imposed rather than agreed, with scarce
      opportunities for participating in clinical decisions. Patients develop
      strategies to take their own decisions and adapting treatment to their daily
      life. CONCLUSIONS: Patients value a relationship model whereby providers listen
      and empathise with their situation, understand their difficulties in treatment
      compliance, encourage them, and adapt recommendations to the personal and
      emotional circumstances of each patient. They prefer doctors combining
      professional competence-including relational skills-with humanity and kindness,
      as well as being capable of assuming their co-responsibility in treatment
      success.

PMID- 16790213
TI  - [Commentary: Chronic illnesses: why are we still waiting for Godot?].

PMID- 16790214
TI  - [Primary care asthma treatment: Are we following international consensus (GINA
      2002)?].
AB  - OBJECTIVE: To check whether treatment of asthma patients at our centre coincides
      with international criteria (GINA 2002). DESIGN: Transversal, descriptive study.
      SETTING: Urban primary care team. PARTICIPANTS: Asthma patients over 14 years
      old. MAIN MEASUREMENTS: Review of clinical histories (CH) and analysis of the
      last prescription between November 2002 and May 2003. RESULTS: We reviewed 436
      CH, of which 395 made up the study group. 71.4% (SD, 66.9-75.8) were women.
      Average age was 51.4 (SD, 49.2-53.6). Classification of asthma as function of
      gravity was: intermittent (IA): 30% (25.7-34.3); light persistent (LPA): 24.8%
      (20.7-28.8); moderate persistent (MPA): 30.7% (26.4-35.1); serious persistent
      (SPA): 5.05% (3.19-7.54). Unclassified: 9.4% (6.83-12.5). Correct treatment: IA,
      69.5% (61.6-77.4); LPA, 22.2% (14.4-30.1); MPA, 46.2% (7.8-54.7); SPA, 72.7%
      (49.8-89.3). The most common cause of incorrect treatment in all kinds of asthma
      was the use of international criteria (IC) at inadequate doses: IA, 47.5% (31.5
      63.9); LPA, 73.8% (63.1-82.8); MPA, 38.9% (27.6-51.1); SPA, 33.3% (4.3-77.7). The
      scant use of B2CD.AD was noticeable: IA, 47.5% (31.5-63.9); LPA, 85.7% (76.4
      92.4); MPA, 86.7% (74.3-92.1); SPA, 66.7% (22.3-95.7). The most commonly used
      active principles were salbutamol, salmeterol, budesonide, and montelukast. On
      overall measurement of good treatment, we found that 48.9% (n = 193) of patients
      had a correct prescription. CONCLUSIONS: In primary care, light forms of asthma
      are most commonly monitored. We found low concordance with the GINA 2002
      directives. IC are widely used, but often at incorrect doses. We insist on the
      importance of classifying asthma according to its gravity in order to prescribe
      the right treatment.

PMID- 16790215
TI  - [Clinical error and adverse events: Primary care doctors perception].
AB  - OBJECTIVE: To evaluate how primary care physicians perceive and face clinical
      errors (CE) and/or adverse events (AE). DESIGN: Cross-sectional study (personal
      mail survey). SETTING. Primary care physicians from "Ambit Costa de Ponent."
      PARTICIPANTS: All doctors with tenure from this area (717). MAIN MEASUREMENTS:
      Standardized questionnaire with error and adverse event frequencies. We compared
      answers considering age, gender, family medicine residency, "deniers" (never make
      a mistake), "perceptive" (admitting a mistake in the last year), "hyper
      perceptive" (28 or more errors/adverse events a year), "internal locus of
      control" (admitting personal reasons in errors), and "hypersecure" (>7 points out
      of 10 in clinical security on Likert scale). RESULTS: Two hundred thirty eight
      physicians (33.2%) with an average age of 42.6 (95% CI, 41.6-43.6) replied. The
      28% were "deniers" (95% CI, 22.34-34.26), 67% "perceptive" (95% CI, 60.79-73.23),
      7.4% "hyperperceptive" (95% CI, 4.41-11.44), 6% had "internal locus of control"
      (95% CI, 3.34-9.91), and 23.4% were "hypersecure" (95% CI, 18.14-29.22). Every
      doctor had on average 10.6 adverse events yearly, mainly drug side-effects (37%)
      (95% CI, 35.36-39.15), and diagnostic delay in oncology scenarios (33%) (95% CI,
      31.16-34.85). The most common reaction to an error was to try and contact the
      patient (80%) (95% CI, 73.24-85.73) and to communicate the case to the team
      (41.4%) (95% CI, 33.97-49.22). CONCLUSIONS: AE and CE were recognized as
      frequent, but a third of doctors affirmed they never made a mistake. Young male
      physicians, unlike senior ones, communicate mistakes to the team. "Internal locus
      of control" and "hyperperceptive" professionals tended to have stronger emotional
      reactions after committing errors. Physicians felt less secure with ophthalmology
      and ENT problems; and older doctors added to these dermatology and palliative
      care.

PMID- 16790216
TI  - [Attitudes of spanish primary care doctors to migraine].
AB  - OBJECTIVES: To find the attitude of Spanish primary care (PC) doctors to
      migraine, their ability to solve the problem and the therapy guidelines used.
      DESIGN: Transversal, descriptive study by means of a questionnaire sent out by
      mail. SETTING: PC doctors in Spain. PARTICIPANTS: A total of 721 PC doctors from
      all the health services. MAIN MEASUREMENTS: Approach, specialist referral,
      therapy preferences, and interest in training were measured through the
      questionnaire. RESULTS: Of the 1185 doctors to whom the questionnaire was sent
      out, 721 replied (60.8%); 69.8% showed very great or great interest in migraines;
      12.2% referred to a specialist the first episode of migraine without aura; and
      42.3%, of migraine with aura. The 32.3% referred the first episode of daily
      chronic migraine; and 56%, when linked to analgesic abuse. Paracetamol is the
      preferred medication for 61.2% of doctors in treating light migraine; NSAIDs are
      for 63.9% in moderate migraine; and tryptans are for 88.1% in severe cases. In
      pressure migraine, NSAIDs are preferred by 38%. Over 75% stated great or very
      great interest in training. CONCLUSIONS: Interest in migraines is high. There is
      considerable room for improvement in the capacity to solve certain kinds of
      migraines, especially chronic daily migraines. Some therapeutic guidelines are
      questionable. This, alongside the interest of doctors in training, points to the
      appropriateness of conducting training on this question.

PMID- 16790217
TI  - [Selection of quality indicators for primary care prescription through a
      consensus group].
AB  - OBJECTIVE: To work out a system of indicators for improvement of primary care
      prescription, by incorporating the values and views of the professionals issuing
      prescriptions. DESIGN: Qualitative technique to search for consensus among
      experts, based on nominal groups. SETTING: All primary care areas in the Health
      Service of Aragon, Spain. PARTICIPANTS: Primary care doctors, doctors in primary
      care management teams, specialists, primary care pharmacists. METHOD: Two
      parallel groups involving a total of 24 experts were formed. In the session these
      questions were posed: "what indicators focusing on the drug and what indicators
      relating diagnosis and treatment do you think most useful for evaluating
      prescription quality?" Each panellist put forward indicators that were then
      discussed and placed on a scale of 1 to 9. RESULTS: One hundred and thirty six
      indicators were generated, 81 drug-focused and 55 relating diagnosis and
      treatment; 56% were given a weighting above 5. The 2 groups coincided in 11
      cases. The most valued indicators were generally those that brought a greater
      degree of consensus. CONCLUSION: It is feasible, through this technique, to
      produce a set of agreed indicators for evaluating primary care doctors'
      prescription.

PMID- 16790218
TI  - [A 'good death'. A euphemism or an objective that can be evaluated?].

PMID- 16790220
TI  - [Epidemiology of age-related macular degeneration. Situation in Spain].

PMID- 16790219
TI  - [Monitoring a home care cohort].
AB  - OBJECTIVES: To evaluate home care by primary care teams for people over 65 years
      old with chronic conditions, in order to identify improvement opportunities. To
      identify patient and care variables associated with cognitive and functional
      impairment, nursing home admission, attendance at casualty units, hospital
      admission and death. DESIGN: Analytic study of the follow-up of a cohort for 3
      years. SETTING: Primary health care teams in Catalonia, Spain. PATIENTS: One
      thousand three hundred patients over 65 with chronic pathologies and cared for by
      home care programmes in Catalonia. MAIN MEASUREMENTS: The following will be
      recorded annually: health status (Charlson, Barthel, Pfeiffer, Braden, and
      Gijon), data on the carer (Zarit), care received (social and health), self
      perception of health (SF-12), Casualty attendance, short-term admissions and the
      final results, i.e. death or definitive admission to a nursing home or hospital.
      The statistical analyses will be based on logistic regression and a survival
      analysis. CONCLUSIONS: The study should reveal patient characteristics with
      prognostic value, as well as identify the social and health factors related to
      better survival and lower consumption of health and social resources.

PMID- 16790221
TI  - [Could hiring more locums be a tool to have more rational drug prescriptions?].

PMID- 16790222
TI  - [Prevalence of burnout and linked variables in primary care doctors in Burgos].

PMID- 16790223
TI  - [Factors that affect recruitment for a clinical trial in primary care].

PMID- 16790224
TI  - [Post-menopausal osteoporosis and ultrasound treatment].

PMID- 16790225
TI  - [Consequences of self-medication with prescription drugs].

PMID- 16790226
TI  - Estimation of non-linear growth models by linearization: a simulation study using
      a Gompertz function.
AB  - A method based on Taylor series expansion for estimation of location parameters
      and variance components of non-linear mixed effects models was considered. An
      attractive property of the method is the opportunity for an easily implemented
      algorithm. Estimation of non-linear mixed effects models can be done by common
      methods for linear mixed effects models, and thus existing programs can be used
      after small modifications. The applicability of this algorithm in animal breeding
      was studied with simulation using a Gompertz function growth model in pigs. Two
      growth data sets were analyzed: a full set containing observations from the
      entire growing period, and a truncated time trajectory set containing animals
      slaughtered prematurely, which is common in pig breeding. The results from the 50
      simulation replicates with full data set indicate that the linearization approach
      was capable of estimating the original parameters satisfactorily. However,
      estimation of the parameters related to adult weight becomes unstable in the case
      of a truncated data set.

PMID- 16790227
TI  - Variance components for survival of piglets at farrowing using a reduced animal
      model.
AB  - Farrowing survival is usually analysed as a trait of the sow, but this precludes
      estimation of any direct genetic effects associated with individual piglets. In
      order to estimate these effects, which are particularly important for sire lines,
      it is necessary to fit an animal model. However this can be computationally very
      demanding. We show how direct and maternal genetic effects can be estimated with
      a simpler analysis based on the reduced animal model and we illustrate the method
      using farrowing survival information on 118,193 piglets in 10,314 litters. We
      achieve a 30% reduction in computing time and a 70% reduction in memory use, with
      no important loss of accuracy. This use of the reduced animal model is not only
      of interest for pig breeding but also for poultry and fish breeding where large
      full-sib families are performance tested.

PMID- 16790228
TI  - On the expected relationship between inbreeding, fitness, and extinction.
AB  - We assessed the expected relationship between the level and the cost of
      inbreeding, measured either in terms of fitness, inbreeding depression or
      probability of extinction. First, we show that the assumption of frequent,
      slightly deleterious mutations do agree with observations and experiments, on the
      contrary to the assumption of few, moderately deleterious mutations. For the same
      inbreeding coefficient, populations can greatly differ in fitness according to
      the following: (i) population size; larger populations show higher fitness (ii)
      the history of population size; in a population that recovers after a bottleneck,
      higher inbreeding can lead to higher fitness and (iii) population demography;
      population growth rate and carrying capacity determine the relationship between
      inbreeding and extinction. With regards to the relationship between inbreeding
      depression and inbreeding coefficient, the population size that minimizes
      inbreeding depression depends on the level of inbreeding: inbreeding depression
      can even decrease when population size increases. It is therefore clear that to
      infer the costs of inbreeding, one must know both the history of inbreeding (e.g.
      past bottlenecks) and population demography.

PMID- 16790229
TI  - Recording strategies and selection potential of feed intake measured using the X
      ray method in rainbow trout.
AB  - This study examines the way long-term feed intake should be recorded accurately
      for selective breeding purposes, and estimates selection potential in feed intake
      using the X-ray method to record individual daily feed intake in rainbow trout
      (Oncorhynchus mykiss). The analysis showed that the point estimates of daily feed
      intake displayed low repeatabilities (r = 0.09-0.32). This indicates that a
      minimum of three repeated records were needed to accurately record average feed
      intake at a fixed age. To effectively breed for feed intake over the whole
      growing period, it is necessary to determine average feed intake at different
      ages, since there were only moderate phenotypic and genetic correlations between
      average daily feed intake recorded at 140 g, 750 g and 2000 g wet mass.
      Heritability for average daily feed intake was low (average h(2) = 0.10),
      indicating that modest genetic changes can be obtained in response to selection.
      It was concluded that selection to genetically change long-term feed intake can
      be successful, yet repeated observations at several life stages are needed to
      ensure the accuracy of feed intake estimates and the efficiency of selection.

PMID- 16790230
TI  - Phylogeographic study of brown trout from Serbia, based on mitochondrial DNA
      control region analysis.
AB  - In order to illuminate the phylogeography of brown trout (Salmo trutta)
      populations in the Balkan state of Serbia, the 561 bp 5'-end of mtDNA control
      region of 101 individuals originating from upland tributaries of the Danubian,
      Aegean and Adriatic drainages were sequenced and compared to corresponding brown
      trout sequences obtained in previous studies. Among 15 haplotypes found, 14 were
      considered native, representing the Danubian and Adriatic lineages of the brown
      trout, while one haplotype (ATcs1), found only in two individuals originating
      from two stocked rivers, corresponded to the Atlantic lineage and was considered
      introduced. Native haplotypes exhibited a strong geographic pattern of
      distribution: the Danubian haplotypes were strictly confined to the Danubian
      drainage, while the Adriatic haplotypes dominated in the Aegean and Adriatic
      drainages; most of the total molecular variance (69%) was attributed to
      differences among the drainages. Phylogenetic reconstruction, supplemented with
      seven haplotypes newly described in this study, suggested a sister position of
      the Atlantic-Danubian and Adriatic-Mediterranean-marmoratus ("southern")
      phylogenetic group, and pointed to the existence of a distinct clade, detected
      within the "southern" group. The data obtained confirmed our expectation of the
      existence of high genetic diversity in Balkan trout populations, and we recommend
      more widespread surveys covering trout stocks from the region.

PMID- 16790231
TI  - OLA-DRB1 microsatellite variants are associated with ovine growth and
      reproduction traits.
AB  - The DRB1 intron 2 (GT)(n)(GA)(m) microsatellite was genotyped in experimental
      flocks of seven Merinoland rams and 249 ewes as well as their offspring (381
      lambs) from consecutive lambings. A total of 16 DRB1 alleles were detected,
      ranging between 353 and 857 bp. In comparison with carriers of other alleles, the
      ewes carrying the predominant 411 bp allele had higher values of all the recorded
      fertility traits. For ewes carrying the 394 and 857 bp alleles, the birth weight
      of lambs was about 400 g higher as compared to the residual group of ewes. The
      observed associations could be due to differences in disease resistance, cell
      recognition or tissue differentiation between carriers of various MHC haplotypes
      which can in turn affect individual fertility and growth performance.

PMID- 16790232
TI  - Sol-gel based surface modification of electrodes for electro analysis.
AB  - In chemical analysis and electrochemical catalysis modified electrodes have been
      used in a wide range. In addition to the several methods of electrode
      modification reported in literature, the sol-gel route offers a possibility of
      preparing ceramic like films under rather mild conditions. This enhances the
      possibility of incorporation of temperature sensitive particles such as enzymes,
      microorganisms, proteins and several other biomolecules into such composite
      layers, resulting in very inert and stable matrices useful for analytical
      applications. The present paper, in addition to providing an overview of the
      various analytical applications of sol-gel processes, presents the fabrication
      and evaluation, of a novel sol-gel based potentiometric sensor for pH
      measurement. The performance characteristics of the sol-gel based pH sensor is
      evaluated using buffers in the pH range 2-10 prepared using standard buffer
      compositions reported in literature. The results show a linear correlation
      between negative logarithm of hydrogen ion concentration and measured millivolt
      response.

PMID- 16790233
TI  - An optimized ecotilling protocol for polyploids or pooled samples using a
      capillary electrophoresis system.

PMID- 16790234
TI  - Analysis of dental anomalies in the Siberian mole, Talpa altaica (Insectivora,
      Talpidae).
AB  - We re-examined tooth variation in specimens of the Siberian mole, Talpa altaica,
      from the collection of the Siberian Zoological Museum and discuss the mechanisms
      of dental evolution. The number of teeth counted in 1789 specimens ranged from 34
      to 47, and supernumerary, absent, and connate teeth were observed. The most
      frequent tooth anomaly was an absent tooth in the premolar region (200 maxillary
      first premolars and 190 mandibular third premolars), which does not support
      Fujita and Kirino's terminal reduction hypothesis in the mandible [Fujita T,
      Kirino T. Ha No Kaibougaku. 21st ed. Tokyo: Kanehara Publishers Inc.; 1976 (in
      Japanese)]. Supernumerary teeth were found in premolar rows and in the incisor
      and molar regions. An maxillary fourth molar, positioned distal to the normal
      third molar, was thought to result from a genetically programmed atavistic event
      during the natal stages. Connate teeth were observed only in the premolar rows
      and were thought to have developed with the fusion of two independent tooth
      germs. Connate premolars appeared to result from an expression of an incomplete
      division of tooth germ at an early developmental stage or a reunion of
      independent tooth germs, based on the morphological similarity of the normal and
      supernumerary premolars. These extraordinarily frequent tooth anomalies of T.
      altaica are of much interest both in terms of tooth development and
      classification.

PMID- 16790235
TI  - Quantitative age-related differences in human sublingual gland.
AB  - OBJECTIVE: To quantify morphological age- and gender-related differences in human
      sublingual glands (SLG). DESIGN: Ninety right human SLG from necropsies were
      distributed by gender and age groups. Individuals with ages ranging from 7 months
      to 92 years were divided into Groups I (0-30 years), II (31-60 years) and III (61
      92 years). The glandular volume of each SLG was calculated. The morphometric
      quantifications of the volume density and total volume of acini, ducts, stroma,
      adipose tissue and septa were realized under light microscopy using a Zeiss II
      integration grid with 100 points symmetrically distributed. RESULTS: The
      glandular volume decreased, on average, 33.78% across the groups. The volume
      density (V(V)) of acini reduced 60.54% and of septa 34.82%, being replaced partly
      by an increase of 58.82%, 551.22% and 2,783.33% in the volume density of ducts,
      stroma and adipose tissue, respectively. In absolute terms, with aging, the total
      volume (V(T)) of the acini decreased by 54.04% and by 34.84% in the septa. In
      contrast, the total volume of ducts, stroma and adipose tissue showed increases
      of 62.53%, 363.25% and 2,308.64%, respectively. Both the V(V) and the V(T) of
      acini, ducts, stroma and adipose tissue and the V(V) of septa were statistically
      different with age. No significant difference was observed between genders.
      CONCLUSION: The decrease of parenchyma accompanied by an increase of stroma
      observed here in SLG is a common feature of aging in human salivary glands.

PMID- 16790236
TI  - Recent progress on obtaining theoretical and experimental support for the "E
      pathway hypothesis" of coupled transmembrane electron and proton transfer in
      dihaem-containing quinol:fumarate reductase.
AB  - Reconciliation of apparently contradictory experimental results obtained on the
      quinol: fumarate reductase (QFR), a dihaem-containing respiratory membrane
      protein complex from Wolinella succinogenes, was previously obtained by the
      proposal of the so-called E-pathway hypothesis. According to this hypothesis,
      transmembrane electron transfer via the haem groups is strictly coupled to co
      transfer of protons via a transiently established, novel pathway, proposed to
      contain the side chain of residue Glu-C180 and the distal haem ring-C propionate
      as the most prominent components. This hypothesis has recently been supported by
      both theoretical and experimental results. Multiconformation continuum
      electrostatics calculations predict Glu-C180 to undergo a combination of proton
      uptake and conformational change upon haem reduction. Strong experimental support
      for the proposed role of Glu-C180 in the context of the "E-pathway hypothesis" is
      provided by the effects of replacing Glu-C180 with Gln or Ile by site-directed
      mutagenesis, the consequences of these mutations for the viability of the
      resulting mutants, together with the structural and functional characterisation
      of the corresponding variant enzymes, and the comparison of redox-induced Fourier
      transform infrared (FTIR) difference spectra for the wild type and Glu-C180-->Gln
      variant. A possible haem propionate involvement has recently been supported by
      combining (13)C-haem propionate labelling with redox-induced FTIR difference
      spectroscopy.

PMID- 16790237
TI  - Nicotine regulates SH-SY5Y neuroblastoma cell proliferation through the release
      of brain-derived neurotrophic factor.
AB  - Nicotine has been shown to produce some beneficial effects in neurodegenerative
      disorders, and several studies have suggested that these effects may be mediated
      in part through the action of the neurotrophic factor BDNF. To further elucidate
      the interaction between nicotine and BDNF, we examined the effect of nicotine on
      the proliferation of the neuroblastoma cell line SH-SY5Y, which, following
      differentiation with retinoic acid, expresses both nicotinic receptors and the
      receptor for BDNF, TrkB. Both nicotine and the nicotinic alpha-7 selective
      agonist AR-17779 significantly increased cell proliferation albeit with bell
      shaped dose-response kinetics. The blockade of this effect with either the alpha
      7 nicotinic antagonist methyllycaconitine or the non-selective nicotinic
      antagonist mecamylamine indicated that the effect was mediated by nicotinic
      receptors. Prior addition of neutralising BDNF antibodies or of the tyrosine
      kinase inhibitor K252A (200 nM) completely blocked nicotine-induced
      proliferation, suggesting the involvement of TrkB signalling in the mediation of
      the effect. Nicotine also enhanced both the secretion of BDNF from the SH-SY5Y
      and cell surface density of TrkB receptors. These effects were abolished by
      pretreatment with MLA. These data indicate that activation of nicotinic receptors
      has effects upon the BDNF-TrkB pathway, inducing cell proliferation by promoting
      the release of BDNF, which in turn activates TrkB receptors.

PMID- 16790238
TI  - Primary biliary cirrhosis is not a clinical condition for increased carbohydrate
      deficient transferrin: experience with four independent CDT analysis methods.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is considered as an important cause
      for increased carbohydrate-deficient transferrin (CDT). The underlying
      pathomechanism is difficult to explain by the pathogenesis and/or consequences of
      PBC. We tested whether PBC causes increased CDT results with current CDT analysis
      methods and, if so, whether this depends on the CDT analysis principle. METHODS:
      48 serum samples from PBC patients were analyzed by HPLC, microcolumn CDT and non
      CDT fractionation followed by a turbidimetric immunoassay, particle-enhanced
      immunonephelometry with monoclonal CDT antibodies, and capillary electrophoresis.
      The test-specific decision limits were used for categorization of the CDT
      analysis results into normal and increased values. RESULTS: HPLC: 47 normal/1
      increased, microcolumn+TIA: 46 normal/2 increased, particle-enhanced
      immunonephelometry: 41 normal/7 increased, capillary electrophoresis: 48 normal
      CDT results. After combining an immunological CDT test (microcolumn+TIA or
      particle-enhanced immunonephelometry) as the screening method with a physico
      chemical CDT test (HPLC or electrophoresis) as the confirmatory method, 1 case
      remained with increased CDT values by the screening (value 2.6%, cut-off 2.5%,
      particle-enhanced immunonephelometry) and confirmatory (value 1.8%, cut-off
      1.75%, HPLC) analysis. CONCLUSIONS: PBC should no longer be overstressed as an
      important cause for false-positive CDT results regarding chronic alcohol abuse.
      In the presence of odd CDT results, PBC should be considered in the anamnestic
      exploration. However, PBC is not by itself a cause for increased CDT values.

PMID- 16790239
TI  - Maternal-neonatal serum paraoxonase 1 activity in relation to the mode of
      delivery.
AB  - AIM: To investigate the effect of the mode of labour and delivery on the total
      antioxidant status (TAS) and the paraoxonase 1 (PON 1) serum activity in mothers
      and their newborns. SUBJECTS AND METHODS: One hundred six women with normal
      pregnancy were divided into 4 groups: group A (n = 28) with normal labour and
      vaginal delivery (VG), group B (n = 25) with scheduled caesarean section (CS),
      group C (n = 26) with "emergency" CS and group D (n = 27) with prolonged labour +
      VG. Blood was obtained from the mothers at the beginning of the labour process
      and immediately after delivery (pre- and post-delivery) as well as from the
      umbilical cord (CB). PON 1 activity and blood chemistry were determined using the
      Bayer Advia 1650 Clinical Chemistry System, whereas TAS levels were measured
      spectrophotometrically at 450 min in microtiter plates. RESULTS: TAS levels were
      similar pre-delivery and low in CB in all the groups. In contrast, TAS levels
      were remarkably reduced in group C and in group D post-delivery whereas they were
      nearly unchanged in group B and just lowered in group A, at the same time of
      study. PON 1 activity was practically unaltered in group A and group B pre- vs.
      post-delivery. Interestingly, the enzyme activity was remarkably decreased in
      group C (222 +/- 16 vs. 153 +/- 14 U/min/mL) and group D (216 +/- 16 vs. 135 +/-
      15 U/min/mL, p < 0.001) as compared with those of the other groups at the same
      time of study. Additionally, PON 1 activity was higher in the newborns of group A
      and group B than those in group C and group D. TAS and HDL positively correlated
      with PON 1 activity. CONCLUSION: The low TAS levels and the decreased PON 1
      activity, which were found in groups C and D post-delivery, may be due to the
      increased production of free radicals, during long-lasting labour + VG and
      obstructive labour + CS. PON 1 activity was low in CB irrespectively of the mode
      of delivery, probably due to the low lipid levels in the serum of the umbilical
      cord. Neonates born with normal delivery or scheduled CS are benefited with a
      higher antiatherogenic enzyme activity perinatally.

PMID- 16790240
TI  - Position and time specify the migration of a pioneering population of olfactory
      bulb interneurons.
AB  - We defined the cellular mechanisms for genesis, migration, and differentiation of
      the initial population of olfactory bulb (OB) interneurons. This cohort of early
      generated cells, many of which become postmitotic on embryonic day (E) 14.5,
      differentiates into a wide range of mature OB interneurons by postnatal day (P)
      21, and a substantial number remains in the OB at P60. Their precursors
      autonomously acquire a distinct identity defined by their position in the lateral
      ganglionic eminence (LGE). The progeny migrate selectively to the OB rudiment in
      a pathway that presages the rostral migratory stream. After arriving in the OB
      rudiment, these early generated cells acquire cellular and molecular hallmarks of
      OB interneurons. Other precursors--including those from the medial ganglionic
      eminence (MGE) and OB--fail to generate neuroblasts with similar migratory
      capacity when transplanted to the LGE. The positional identity and migratory
      specificity of the LGE precursors is rigidly established between E12.5 and E14.5.
      Thus, the pioneering population of OB interneurons is generated from spatially
      and temporally determined LGE precursors whose progeny uniquely recognize a
      distinct migratory trajectory.

PMID- 16790241
TI  - Brain-derived neurotrophic factor induces post-lesion transcommissural growth of
      olivary axons that develop normal climbing fibers on mature Purkinje cells.
AB  - In the adult mammalian central nervous system, reinnervation and recovery from
      trauma is limited. During development, however, post-lesion plasticity may
      generate alternate paths providing models to investigate factors that promote
      reinnervation to appropriate targets. Following unilateral transection of the
      neonatal rat olivocerebellar pathway, axons from the remaining inferior olive
      reinnervate the denervated hemicerebellum and develop climbing fiber arbors on
      Purkinje cells. However, the capacity to recreate this accurate target
      reinnervation in a mature system remains unknown. In rats lesioned on day 15
      (P15) or 30 and treated with intracerebellar injection of brain-derived
      neurotrophic factor (BDNF) or vehicle 24 h later, the morphology and organisation
      of transcommissural olivocerebellar reinnervation was examined using neuronal
      tracing and immunohistochemistry. In all animals BDNF, but not vehicle, induced
      transcommissural olivocerebellar axonal growth into the denervated
      hemicerebellum. The distribution of reinnervating climbing fibers was not
      confined to the injection sites but extended throughout the denervated hemivermis
      and, less densely, up to 3.5 mm into the hemisphere. Transcommissural
      olivocerebellar axons were organised into parasagittal microzones that were
      almost symmetrical to those in the right hemicerebellum. Reinnervating climbing
      fiber arbors were predominantly normal, but in the P30-lesioned group 10% were
      either branched within the molecular layer forming a smaller secondary arbor or
      were less branched, and in the P15 lesion group the reinnervating arbors extended
      their terminals almost to the pial surface and were larger than control arbors (P
      < 0.02). These results show that BDNF can induce transcommissural olivocerebellar
      reinnervation, which resembles developmental neuroplasticity to promote
      appropriate target reinnervation in a mature environment.

PMID- 16790242
TI  - Carotenoid stoichiometry in the LH2 crystal: no spectral evidence for the
      presence of the second molecule in the alpha/beta-apoprotein dimer.
AB  - In this work we have investigated the carotenoid-protein interactions in LH2
      complexes of Rhodopseudomonas acidophila both in "free in solution" mixed
      micelles and in three-dimensional crystals by Raman spectroscopy in resonance
      with the carotenoid (Car) molecules. We show that the Car molecules when bound to
      their binding pockets show no significant differences when the complexes are
      "free in solution" or packed in crystalline arrays. Furthermore, there is no
      significant wavelength dependence in the Raman spectrum of the Car molecules of
      LH2. This indicates that there is only one Car configuration in LH2 and thus only
      one molecule per alpha/beta-heterodimer.

PMID- 16790243
TI  - Identification of a dithiol-dependent nucleoside triphosphate hydrolase in
      Sarcocystis neurona.
AB  - A putative nucleoside triphosphate hydrolase (NTPase) gene was identified in a
      database of expressed sequence tags (ESTs) from the apicomplexan parasite
      Sarcocystis neurona. Analysis of culture-derived S. neurona merozoites
      demonstrated a dithiol-dependent NTPase activity, consistent with the presence of
      a homologue to the TgNTPases of Toxoplasma gondii. A complete cDNA was obtained
      for the S. neurona gene and the predicted amino acid sequence shared 38% identity
      with the two TgNTPase isoforms from T. gondii. Based on the obvious homology, the
      S. neurona protein was designated SnNTP1. The SnNTP1 cDNA encodes a polypeptide
      of 714 amino acids with a predicted 22-residue signal peptide and an estimated
      mature molecular mass of 70kDa. Southern blot analysis of the SnNTP1 locus
      revealed that the gene exists as a single copy in the S. neurona genome, unlike
      the multiple gene copies that have been observed in T. gondii and Neospora
      caninum. Analyses of the SnNTP1 protein demonstrated that it is soluble and
      secreted into the culture medium by extracellular merozoites. Surprisingly,
      indirect immunofluorescence analysis of intracellular S. neurona revealed apical
      localisation of SnNTP1 and temporal expression characteristics that are
      comparable with the microneme protein SnMIC10. The absence of SnNTP1 during much
      of endopolygeny implies that this protein does not serve a function during
      intracellular growth and development of S. neurona schizonts. Instead, SnNTP1 may
      play a role in events that occur during or proximal to merozoite egress from
      and/or invasion into cells.

PMID- 16790244
TI  - Reduction and enhancement of Plasmodium falciparum transmission by endemic human
      sera.
AB  - Transmission of Plasmodium falciparum from man to mosquito can be affected by
      human sera. Whereas serum-dependent reduction of transmission has been shown to
      be reproducible, there is limited evidence for enhancement of transmission. We
      aimed to assess the prevalence and reproducibility of transmission enhancement
      (TE) by human sera from different geographic areas (n = 642), in comparison with
      the capacity for transmission reduction (TR). The overall prevalence of TE (7%)
      was lower than that of TR (48%) and its effect generally weaker but reproducible
      in repeated measurements. TR but not TE showed a significant association with the
      presence of serum antibodies against Pfs48/45 and a non-significant trend to the
      presence of anti-Pfs230 antibodies.

PMID- 16790245
TI  - Arrays of lipid bilayers and liposomes on patterned polyelectrolyte templates.
AB  - This paper presents novel methods to produce arrays of lipid bilayers and
      liposomes on patterned polyelectrolyte multilayers. We created the arrays by
      exposing patterns of poly(dimethyldiallylammonium chloride) (PDAC), polyethylene
      glycol (m-dPEG) acid, and poly(allylamine hydrochloride) (PAH) on polyelectrolyte
      multilayers (PEMs) to liposomes of various compositions. The resulting interfaces
      were characterized by total internal reflection fluorescence microscopy (TIRFM),
      fluorescence recovery after pattern photobleaching (FRAPP), quartz crystal
      microbalance (QCM), and fluorescence microscopy. Liposomes composed of 1,2
      dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3
      phosphate (monosodium salt) (DOPA) were found to preferentially adsorb on PDAC
      and PAH surfaces. On the other hand, liposome adsorption on sulfonated
      poly(styrene) (SPS) surfaces was minimal, due to electrostatic repulsion between
      the negatively charged liposomes and the SPS-coated surface. Surfaces coated with
      m-dPEG acid were also found to resist liposome adsorption. We exploited these
      results to create arrays of lipid bilayers by exposing PDAC, PAH and m-dPEG
      patterned substrates to DOPA/DOPC vesicles of various compositions. The patterned
      substrates were created by stamping PDAC (or PAH) on SPS-topped multilayers, and
      m-dPEG acid on PDAC-topped multilayers, respectively. This technique can be used
      to produce functional biomimetic interfaces for potential applications in
      biosensors and biocatalysis, for creating arrays that could be used for high
      throughput screening of compounds that interact with cell membranes, and for
      probing, and possibly controlling, interactions between living cells and
      synthetic membranes.

PMID- 16790246
TI  - Modification to the cumulant analysis of polydispersity in quasielastic light
      scattering data.
AB  - The electric field correlation function of light scattered from a polydispersed
      population of spherical particles having log-normal distribution with varying
      polydispersity is simulated. The correlation function with different
      polydispersity is compared with the method of cumulants over a wide range of
      correlation time. The large positive deviation of the method of cumulants at long
      correlation time is identified. This necessitates the truncation of the data at
      long correlation time or use of an appropriate weighting function to eliminate
      errors in the analysis. A modified cumulant analysis is used to overcome the
      limitation of truncating the correlation function. QELS data from polydisperse
      samples of micelles, liposomes and polyaniline nanoparticles are compared using
      the two methods. This method can be extended to the analysis of other multi
      exponential decays such as stress relaxation, positron annihilation and NMR
      relaxation.

PMID- 16790247
TI  - Identification of the elastic properties of an artificial capsule membrane with
      the compression test: effect of thickness.
AB  - The mechanical properties of a capsule membrane are evaluated by means of a
      compression experiment between two parallel plates. Since large deformations of
      the membrane are involved, the choice of the wall material constitutive law is
      essential. In this paper, we explore different classical laws to describe the
      behavior of the membrane and evaluate also the limit of application of the thin
      shell approximation. A numerical study of the compression process is performed
      using Abaqus software and an inverse method is used to identify the material
      constants of the constitutive laws. The comparison between the model predictions
      and experimental measurements on capsules with serum albumin-alginate membranes,
      indicates that the thin shell approximation is valid only for thickness to radius
      ratios up to 5% and that thick membranes obey non linear elastomer type
      constitutive laws. The Young modulus of the membrane material is found to
      increase non-linearly with membrane thickness, thus indicating that fabrication
      of thicker serum albumin-alginate walls results in capsules stiffer than
      expected.

PMID- 16790248
TI  - Temperature dependence of thermodynamic activity in volatile anesthetics:
      correlation between anesthetic potency and activity.
AB  - Temperature dependence of the saturated concentration and the activity
      coefficient of anesthetics (1-propanol, diethyl ether, chloroform, and halothane)
      in water were evaluated using vapor pressure and H NMR measurement. We found that
      these physical values (quantities) correlate with anesthetic potencies estimated
      according to the thermodynamic equilibrium model. The anesthetic potency for
      hydrophilic anesthetic (diethyl ether) decreased with decreasing temperature
      because of the temperature specificity of this saturated concentration. In
      contrast, potencies of hydrophobic anesthetics (chloroform and halothane)
      increased with decreasing temperature because of the temperature specificity of
      those activity coefficients. By assuming that anesthetics interact with hydrated
      water of cell membranes, the temperature dependence of anesthetic potencies in
      vivo is qualitatively explicable.

PMID- 16790249
TI  - ACE inhibitor raps CD26/dipeptidylpeptidase IV knuckles for cytokine EPC
      mobilization.

PMID- 16790250
TI  - Paroxetine treatment of compulsive hoarding.
AB  - OBJECTIVE: Compulsive hoarding, found in many patients with obsessive-compulsive
      disorder (OCD), has been associated with poor response to serotonin reuptake
      inhibitor (SRI) medications in some reports. However, no prior study has
      quantitatively measured response to standardized pharmacotherapy in compulsive
      hoarders. We sought to determine whether compulsive hoarders would respond as
      well as non-hoarding OCD patients to the SRI, paroxetine. METHODS: Seventy-nine
      patients with OCD (32 patients with the compulsive hoarding syndrome and 47
      patients without prominent hoarding symptoms) were treated openly with paroxetine
      (mean dose 41.6+/-12.8 mg/day; mean duration 80.4+/-23.5 days) according to a
      standardized protocol, from 3/1993 to 7/2005. All subjects were free of
      psychotropic medication for at least four weeks prior to study entry. No
      psychotherapy or psychotropic medications except paroxetine were allowed during
      the study period. Subjects were assessed before and after treatment with the Yale
      Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale
      (HDRS), Hamilton Anxiety Scale (Ham-A), Global Assessment Scale (GAS), and
      Clinical Global Impression/Improvement (CGI) scale. RESULTS: Both compulsive
      hoarders and non-hoarding OCD patients improved significantly with treatment
      (p<0.001), with nearly identical changes in Y-BOCS, HDRS, Ham-A, and GAS scores.
      There were no significant differences between groups in the proportions of
      patients who completed or responded to treatment. Hoarding symptoms improved as
      much as other OCD symptoms. CONCLUSIONS: Compulsive hoarders responded as well to
      paroxetine treatment as non-hoarding OCD patients, suggesting that SRI
      medications are effective for compulsive hoarding. Controlled trials of SRI
      medications for compulsive hoarding are now warranted.

PMID- 16790251
TI  - Heart rate dynamics in iNOS knockout mice.
AB  - Nitric oxide has both an inhibitory and excitatory role in the regulation of pre
      ganglionic sympathetic neurons, involving the iNOS and nNOS systems respectively.
      The aim of the present study was to examine cardiovascular autonomic activity in
      iNOS knockout mice using spectral analysis of heart rate variability (HRV), and
      to determine the role of iNOS in altered HRV in endotoxaemia. Electrocardiograms
      were recorded in anaesthetised mice, and the R-R intervals digitized for spectral
      analysis of HRV and cardiac rhythm regularity using sample entropy analysis. The
      basal heart rate was higher in iNOS knockout mice compared with controls (465+/-8
      vs 415+/-13 beat/min P<0.05), with a significant increase in the low frequency
      power of HRV spectra in iNOS knockout mice compared with controls (49.4+/-4.3 vs
      33.8+/-5.6 normalized units, P<0.05), consistent with increased cardiac
      sympathetic activity. Endotoxaemia is known to decrease HRV, but the role of iNOS
      is unknown. LPS (20 mg/kg i.p) increased basal heart rate in both wild type and
      iNOS knockout mice, but caused a depression of HRV and sample entropy in both
      groups. Studies in isolated beating atria showed that the changes of HRV under
      basal or post-LPS conditions disappeared in vitro, suggesting that the autonomic
      system is responsible for altered HRV. We conclude that disruption of iNOS gene
      leads to an increase in the low frequency power of HRV consistent with increased
      cardiac sympathetic activity. These data also demonstrate that LPS-induced
      decrease of HRV is independent of iNOS.

PMID- 16790252
TI  - Atmospheric lead fallout over the last century recorded in Gulf of Lions
      sediments (Mediterranean Sea).
AB  - Six marine sediment cores from the Gulf of Lions continental slope (700-1700 m
      water depth) were analyzed for stable lead isotopes and (210)Pb geochronology in
      order to reconstruct lead atmospheric fallout pattern during the last century.
      The detrital lead contribution is 25 microg g(-1) and the mean sediment
      anthropogenic inventory is 110+/-7 microg cm(-2), a little bit higher than
      atmospheric deposition estimate. Anthropogenic lead accumulation in sediments
      peaked in early 1970s (1973+/-2) in agreement with lead emissions features. For
      the period 1986-1997, the sediment signal also reflect the decrease of
      atmospheric lead described by independent atmospheric fallout investigations. The
      anthropogenic Pb deposition in the late 1990s was similar to the 1950s
      deposition, attesting thus of the output of European environmental policies.

PMID- 16790253
TI  - Accumulation of apocarotenoids in mycorrhizal roots of Ornithogalum umbellatum.
AB  - Colonization of roots of Ornithogalum umbellatum by the arbuscular mycorrhizal
      fungus Glomus intraradices induced the accumulation of different types of
      apocarotenoids. In addition to the mycorrhiza-specific occurrence of
      cyclohexenone derivatives and the "yellow pigment" described earlier, free
      mycorradicin and numerous mycorradicin derivatives were detected in a complex
      apocarotenoid mixture for the first time. From the accumulation pattern of the
      mycorradicin derivatives their possible integration into the continuously
      accumulating "yellow pigment" is suggested. Structure analyses of the
      cyclohexenone derivatives by MS and NMR revealed that they are mono-, di- and
      branched triglycosides of blumenol C, 13-hydroxyblumenol C, and 13-nor-5-carboxy
      blumenol C, some of which contain terminal rhamnose as sugar moiety.

PMID- 16790254
TI  - beta-Carotene accumulation induced by the cauliflower Or gene is not due to an
      increased capacity of biosynthesis.
AB  - The cauliflower (Brassica oleracea L. var. botrytis) Or gene is a rare carotenoid
      gene mutation that confers a high level of beta-carotene accumulation in various
      tissues of the plant, turning them orange. To investigate the biochemical basis
      of Or-induced carotenogenesis, we examined the carotenoid biosynthesis by
      evaluating phytoene accumulation in the presence of norflurazon, an effective
      inhibitor of phytoene desaturase. Calli were generated from young seedlings of
      wild type and Or mutant plants. While the calli derived from wild type seedlings
      showed a pale green color, the calli derived from Or seedlings exhibited intense
      orange color, showing the Or mutant phenotype. Concomitantly, the Or calli
      accumulated significantly more carotenoids than the wild type controls. Upon
      treatment with norflurazon, both the wild type and Or calli synthesized
      significant amounts of phytoene. The phytoene accumulated at comparable levels
      and no major differences in carotenogenic gene expression were observed between
      the wild type and Or calli. These results suggest that Or-induced beta-carotene
      accumulation does not result from an increased capacity of carotenoid
      biosynthesis.

PMID- 16790255
TI  - Modelling of magnetic fields to enhance the performance of an in-plane EMAT for
      laser-generated ultrasound.
AB  - A new magnetic arrangement is described for use with an in-plane electromagnetic
      acoustic transducer (EMAT) for detecting laser-generated ultrasound. The magnetic
      flux density was modelled and validated. Modelling was accomplished in 3D using
      finite element software to predict new magnet spatial distributions. A
      configuration was found which increased the magnetic flux density by a factor of
      1.8+/-0.2, compared to magnetic configurations previously used in conventional
      designs. Model predictions were implemented and confirmed experimentally. As a
      result, laser ultrasound Rayleigh waves have been used to verify the performance
      of this sensor system. It was establish that the EMAT's in-plane sensitivity
      increased, while the frequency bandwidth improvement factor was about 1.9+/-0.2.
      The resonant frequency increased from 6.5 MHz and 16.4 MHz, with both exhibiting
      an extended frequency response well beyond the resonant values. For maximum
      frequency response, it was demonstrated that added elements such as cables may
      have a deleterious effect. In particular the length of the cable, which in turn
      adds capacitance to the overall circuit, will decrease the frequency response of
      the EMAT. The frequency response was compared with a previous sensor, to provide
      an increased resonant frequency factor of 2.5+/-0.2.

PMID- 16790256
TI  - Non-identical patterns of proviral insertions around host transcription units in
      lymphomas induced by different strains of murine leukemia virus.
AB  - In a small sample of 57 retrovirus integration sites (RISs) isolated from 23 end
      stage lymphomas induced in NMRI mice by the B-lymphotropic Akv wt or an enhancer
      mutant hereof, Akv1-99, we identified 14 novel RISs and defined 9 novel CISs
      (common insertion sites). Moreover, when comparing with RISs from tumors induced
      by the T-lymphomagenic SL3-3, we observed that SL3-3 targets RefSeq promoter
      regions with a significantly higher frequency than Akv/Akv1-99 and in an
      orientation-dependent way. Altogether, our results strongly emphasize the
      importance of host genetic background and virus type for retroviral insertion
      mutagenesis screens and suggest that different types of MLV may favor specific
      genomic regions and orientations in order exert optimal effect on target gene
      expression during lymphoma induction and development.

PMID- 16790257
TI  - Genotyping of single Cryptosporidium oocysts in sewage by semi-nested PCR and
      direct sequencing.
AB  - This study describes an approach for genotyping individual Cryptosporidium
      oocysts obtained from sewage. We isolated single immunofluorescent assay (IFA)
      stained Cryptosporidium oocysts from sewage concentrate using glass capillary
      pipettes and inverted epifluorescence microscopy. Each isolated Cryptosporidium
      oocyst was analyzed by semi-nested PCR for the 18S rRNA gene and direct
      sequencing of the PCR products. A total of 74 of 107 oocysts isolated from sewage
      were genotyped successfully. Of the 74 genotyped isolates, 51% (38 oocysts) were
      identified as C. parvum genotype 1, 4% (3 oocysts) of C. parvum VF383 human
      isolates, 20% (15 oocysts) of C. parvum genotype 2, 14% (10 oocysts) of C.
      meleagridis, 7% (5 oocysts) of C. sp. Pig 1, 3% (2 oocysts) of C. sp PG1-26 pig
      isolates and 1% (1 oocyst) of C. parvum CPM1 isolated from mouse. The results of
      this study demonstrate that 18S rRNA-based semi-nested PCR and direct sequencing
      can be used to characterize individual Cryptosporidium oocysts and also to reveal
      the distribution of Cryptosporidium genotypes in environmental waters.

PMID- 16790258
TI  - Occurrence of ionophore antibiotics in water and sediments of a mixed-landscape
      watershed.
AB  - Analytical methods for quantifying three ionophore antibiotics, monensin,
      salinomycin, and narasin, were developed for water and sediment matrices. Sample
      preparation was based on solid-phase extraction (SPE) and high-performance liquid
      chromatography (HPLC) tandem mass spectrometry (MS/MS) was used to separate and
      detect the compounds. Recoveries ranged from 83% to 117% for water and from 51%
      to 105% for sediment in three different concentrations with less than 10% of
      relative standard deviation. The statistical detection limit was 0.001-0.003
      microg/L for water and 0.4-3.6 microg/kg for sediment. Ionophore antibiotics are
      only used to treat coccidiostats for broilers or turkeys, and to increase growth
      and feed efficiency for beef and dairy cattle. Since they are not used for human
      purposes, these compounds can act as markers for the transport of animal
      pharmaceuticals to the watershed. The occurrence of three ionophore compounds was
      determined at five sampling sites along the Cache la Poudre River in Northern
      Colorado representing pristine, urban, and agriculture landscapes. Statistical
      analysis demonstrates that the measured concentration was significantly different
      among sampling sites in different sampling events for both water and sediment. In
      addition, significant differences were observed among different sampling times at
      each sampling site. Furthermore, all three ionophores were found in the sediments
      at much higher concentrations than in water indicating the importance of this
      matrix when determining environmental impacts.

PMID- 16790259
TI  - Oxidation of sulfonamides, macrolides, and carbadox with free chlorine and
      monochloramine.
AB  - The oxidation of 10 antibiotics-carbadox, erythromycin-H(2)O, roxithromycin,
      sulfadimethoxine, sulfamerazine, sulfamethazine, sulfamethizole,
      sulfamethoxazole, sulfathiozole, and tylosin during chlorination and
      monochloramination in laboratory and surface waters was investigated to identify
      kinetics and treatment effectiveness. A kinetic model that incorporates pH-based
      speciation of both oxidant species and sulfonamide antibiotics was developed and
      validated. Specific rate constants for the individual ionic species were
      developed for the dominant reactant pairs. Liquid chromatography/mass
      spectrometry, preceded by solid phase extraction, was used to analyze antibiotics
      in kinetic experiments. With experimental conditions of 25 degrees C and reaction
      times of up to 2 h, an initial concentration of 1 mg/L of free chlorine removed
      an average of 88 percent of the antibiotics over a pH range of 6.1-9.1.
      Monochloramine was less effective at typical drinking water dosage concentrations
      of 3 mg/L, with average removals of 35, 10, and 0 percent at a pH of 6.1, 7.6,
      and 9.1, respectively.

PMID- 16790260
TI  - Photocatalytic degradation of Reactive Red 22 in aqueous solution by UV-LED
      radiation.
AB  - Photocatalytic processes using TiO(2) as a catalyst have attracted extensive
      attention for decomposition of organic contaminants. The determination of optimum
      reactor design and operational conditions are the major concerns for the
      development and potential application of the photocatalytic process. Various
      photoreactor types, photocatalyst arrangements, light sources, and operation
      conditions were reported. This study was focused on the application of the
      ultraviolet light emitting diode (UV-LED) as the UV light source for the
      photocatalytic decomposition of Reactive Red 22 (RR 22). The temporal behavior of
      the photocatalytic decomposition of RR 22 in aqueous solution by the UV
      LED/TiO(2) with a rectangular planar fixed-film reactor operated in a
      recirculation mode was studied under various conditions including initial dye
      concentration, periodic illumination, light intensity, and arrangements of TiO(2)
      coating. The decomposition of RR 22 in aqueous solution by TiO(2) photocatalytic
      processes with the UV-LED was found to be technically feasible with a high TiO(2)
      coated weight (1.135g) and low pH value (pH 2). A Langmuir-Hinshelwood-type
      kinetic equation was adequate for modeling the photocatalytic decomposition of RR
      22 by the UV-LED/TiO(2) photocatalytic processes. The experimental results
      indicated that the photonic efficiency with periodic illumination was much higher
      than those with continuous illumination. The photonic efficiencies with the
      quartz-liquid-catalyst (QLC) arrangement were higher than those with the quartz
      catalyst-liquid (QCL) arrangement for experiments conducted at lower applied
      light intensity; however, the photonic efficiencies for these two arrangements
      were nearly identical for experiments conducted at higher light intensities.

PMID- 16790261
TI  - Quantitative structure activity relationship (QSAR) for toxicity of chlorophenols
      on L929 cells in vitro.
AB  - Quantitative structure activity relationship (QSAR) were developed to predict
      toxicity of chlorophenols by correlating LC50 values with five molecular
      descriptors, chosen to represent lipophilic, electronic and steric effects: the n
      octanol/water partition coefficient (log K(ow)), the constant of Hammett (sigma
      sigma), the acid dissociation constant (pKa), the order valence molecular
      connectivity index (1chi(v)) and the perimeter of the efficacious section (sigma
      D(g)). The results of the regression analysis showed that log K(ow) and sigma
      D(g) are the dominant (canonical) predictive factors in determining toxicity of
      chlorophenols to the cells during 24 h exposures, while log K(ow) was the only
      dominant predictive factor contributing to toxicity during in 48 h exposures.
      Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) were applied to investigate predictive relationships of
      the cytotoxicity of chlorophenols and develop visual 3D-QSAR models. The CoMFA
      model, in which the contribution of the electrostatic field to the biological
      activity was greater than that of the steric field, exhibited both high
      consistency and predictability (r2 = 0.968, Q2 = 0.891 for 24 h exposure; but the
      relationship was poorer for the 48 h exposure: r2 = 0.727, Q2 = 0.394). The
      CoMSIA model used in this study contained three fields: electrostatic,
      hydrophobic and steric, of which the relative contribution to the biological
      activity was 0.767:0.225:0.008. In addition, according to the models for 24 h and
      48 h. The time-dependent toxicity and potential mechanisms for inhibition of L929
      cells was discussed.

PMID- 16790262
TI  - Classification of amyloidosis: misdiagnosing by way of incomplete
      immunohistochemistry and how to prevent it.
AB  - Classification of every individual case of amyloid disease is necessary in order
      to recognize its origin and its possible pathogenesis for therapeutic
      consideration. Classification of the amyloids can be performed in different ways.
      One method primarily exploits serum proteins-but these are risk factors only, and
      therefore render only ancillary information. In principle, one cannot establish
      the diagnosis alone through their use. Another approach analyzes the origin of
      the deposited amyloids, either by extracting the amyloid proteins followed by
      immunochemical or chemical analysis, or by using immunohistochemistry. Based on
      chemical analysis of prototypes of amyloid fibril proteins, we have developed a
      profile of antibodies over the years that specifically identify amyloid in tissue
      sections. These antibodies have been used for years as a routine service for
      clinicians and pathologists in immunohistochemically classifying amyloid found in
      formalin-fixed tissue sections. The typing is always controlled by established
      amyloid classes. In several cases, we have been asked for a second opinion on a
      diagnosed amyloid class. Our own immunohistochemical data were then compared with
      those submitted. These submitted immunohistochemical results represented
      misdiagnoses of amyloid classes in most patients, since the technique performed
      was usually incomplete. It is the purpose of this report to analyze such cases
      and to document some of the typical mistakes. Here, we show how to avoid common
      pitfalls and how one can arrive at a correct diagnosis using immunohistochemistry
      appropriately.

PMID- 16790263
TI  - Treatment and prognosis of post term choriocarcinoma in The Netherlands.
AB  - INTRODUCTION: Antecedent term pregnancy is an adverse prognostic factor in
      Gestational Trophoblastic Disease (GTD). In The Netherlands, patients with post
      term choriocarcinoma are considered high-risk independent of WHO score. In the
      present study, we assessed whether post term choriocarcinoma always has to be
      considered high-risk, requiring first line treatment with combination
      chemotherapy, or whether a subgroup of patients is distinguishable in which
      single-agent Methotrexate is a safe alternative. PATIENTS AND METHODS: The study
      is a retrospective multicenter cohort study. Patients registered by the Dutch
      Working Party on Trophoblastic Disease between 1986 and 2004 with choriocarcinoma
      after a non-molar pregnancy were eligible. Hospital and outpatient records of the
      patients were reviewed. RESULTS: In total, 68 patients with non-molar
      choriocarcinoma were registered of whom 44 had an antecedent term pregnancy. Most
      post term patients (77%) were high-risk according to the WHO staging system. The
      majority of patients presented with metrorraghia and high hCG levels. Lung and
      liver metastases were common (respectively 64% and 28%), probably caused by a
      delay in diagnosis (median interval 16 weeks). Patients were often Methotrexate
      resistant (75%). Overall survival was 86% in patients with a post term
      choriocarcinoma. CONCLUSIONS: Although term pregnancy is an adverse prognostic
      factor in GTD, current survival is comparable to the general survival in high
      risk patients. A subgroup of patients in which monotherapy would be sufficient
      could not be identified. Immediate administration of combination chemotherapy
      seems justified, even in those few cases when scoring systems would suggest low-
      or medium-risk disease.

PMID- 16790264
TI  - Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic
      regimens in advanced refractory epithelial ovarian cancer.
AB  - OBJECTIVES: Bevacizumab (BEV) is a humanized monoclonal antibody against vascular
      endothelial growth factor. We reviewed our experience with BEV in patients with
      recurrent advanced epithelial ovarian cancer who had failed multiple prior
      chemotherapeutic regimens. METHODS: Thirty-two patients not participating in an
      ongoing clinical trial were treated with BEV (15 mg/kg every 3 weeks IV).
      Demographic and clinicopathologic data, clinical outcomes, and adverse events
      were extracted from patient charts. RECIST and CA-125 Rustin criteria were
      retrospectively applied to evaluate response and progression. Median progression
      free survival (PFS) and overall survival (OS) were determined using Kaplan-Meier
      methods. Adverse events were retrospectively categorized using the common
      terminology criteria for adverse events version 3. RESULTS: The median patient
      age was 57 years (range 35-80) with 84% being Caucasian and 50% having a GOG
      performance status of 2. FIGO stages included 80% stage III and 10% stage IV. The
      tumors were mostly grades 2 (29%) and 3 (64%) and serous histological subtype
      (69%). All patients had failed multiple prior cytotoxic chemotherapies (median of
      5 (range 2-10)) prior to BEV. The median duration of follow-up was 4.8 months
      (range 0.4-16.3). Twenty-three patients were treated with BEV alone, 2 received
      BEV with another chemotherapy regimen (5-FU/lecovorin plus oxaliplatin,
      cyclophosphamide), and 8 initially received BEV alone, followed by BEV with
      capcitabine, cyclophosphamide, docetaxel, carboplatin, or weekly paclitaxel. A
      median of 6 cycles (range 1-20) with 196 total doses of BEV was administered. One
      patient was lost to follow-up after cycle 1. We observed a 16% response rate (all
      in those treated with BEV alone) with 62.5% of patients demonstrating stable
      disease. Median OS was 6.9 months, and the median PFS was 5.5 months. Three grade
      3 and no grade 4 adverse events were observed. Grade 3 toxicities included
      hypertension, proteinuria, and enterocutaneous fistula. The fistula occurred
      after 5 cycles of BEV in a patient who had undergone 7 debulking surgeries prior
      to BEV. CONCLUSIONS: BEV is generally well tolerated after multiple prior
      cytotoxic regimens and results in significant clinical benefit among women with
      recurrent ovarian cancer.

PMID- 16790265
TI  - Carcinoma in situ cervicis uteri and inheritance--a Danish twin study.
AB  - OBJECTIVE: To determine the relative environmental and genetic influence in the
      development of carcinoma in situ (CIS) cervicis uteri. METHODS: Retrospective
      follow-up study with record linkage between The Danish Twin Register and The
      Danish Cancer Register. The study base comprises 27,004 female twins from 13,502
      same-sex twin pairs. 5,258 were monozygotic and 8,244 dizygotic twin pairs. The
      statistic measurements are the coincidence ratio and the probandwise concordance
      rate in the two groups of twins with different zygosity. RESULTS: 750 twins were
      diagnosed with CIS cervicis uteri. 291 monozygotic twins came from 275 pairs and
      459 dizygotic twins came from 435 pairs. There were 16 concordant monozygotic
      twin pairs and 24 concordant dizygotic pairs. The probandwise concordance rate
      was 0.11 (0.06-0.16) in monozygotic twins and 0.10 (0.06-0.14) in dizygotic
      twins. CONCLUSION: A family clustering of CIS was demonstrated in both groups of
      zygosity. The probandwise concordance rate was equal in the monozygotic and the
      dizygotic groups, which means that genetic factors are not important in the
      development of the disease. However, a shared environment among twins plays a
      role in the development of CIS cervicis uteri.

PMID- 16790266
TI  - Plasma pregnenolone levels in cynomolgus monkeys following pharmacological
      challenges of the hypothalamic-pituitary-adrenal axis.
AB  - Pregnenolone (PREG) is an endogenous neuroactive steroid that is increased in
      rodent brain and plasma after hypothalamic-pituitary-adrenal (HPA) activation by
      acute stress or ethanol administration. Plasma levels of PREG metabolites are
      altered by pharmacological challenges of the HPA axis, however little is known
      about HPA regulation of PREG levels in monkeys. PREG concentrations were
      determined by radioimmunoassay in plasma samples from cynomolgus monkeys,
      following challenge with naloxone (125 and 375 microg/kg), corticotropin
      releasing factor (CRF; 1 microg/kg), dexamethasone (130 microg/kg),
      adrenocorticotropic hormone (ACTH; 10 ng/kg; 4-6 h after 0.5 mg/kg dexamethasone)
      and ethanol (1.0 and 1.5 g/kg). Naloxone increased PREG levels, while CRF
      appeared to increase metabolism of PREG to deoxycorticosterone (DOC). ACTH,
      administered after dexamethasone, reduced PREG levels, despite an increase in
      plasma cortisol. Ethanol did not alter PREG levels. Changes in PREG levels were
      correlated with changes in DOC levels after naloxone 125 microg/kg, CRF, ethanol
      1.5 g/kg, and dexamethasone challenges. Furthermore, dexamethasone-induced
      changes in PREG levels were correlated with subsequent alcohol intake. These data
      suggest that PREG responses to dexamethasone challenge may represent a trait
      marker of alcohol drinking. The lack of effect of ethanol on PREG levels suggests
      differential regulation in non-human primates vs. rodents.

PMID- 16790267
TI  - Intrahippocampal injections of Tat: effects on prepulse inhibition of the
      auditory startle response in adult male rats.
AB  - The presence of human immunodeficiency virus (HIV-1) in the brain mediates the
      pathogenesis of HIV-associated dementia complex (HAD), partially through the
      viral toxins gp120 and Tat. This study characterized potential deficits in
      sensorimotor gating, as measured by prepulse inhibition (PPI), following
      hippocampal administration of Tat. Adult, male Sprague-Dawley rats were
      bilaterally injected with 50 microg Tat or saline (1 microl volume), into the
      hippocampus. Following 7 weeks of recovery, all animals were tested using the
      auditory startle response (ASR) with habituation, control, and PPI trials.
      Assessment of ASR habituation [100dB(A) white noise stimulus, 70dB(A) background,
      5-min acclimation period, 36 habituation trials with fixed interstimulus interval
      (ISI) of 10 s] demonstrated a significant approximately 50% reduction in the
      overall peak ASR amplitude, but no change in peak ASR latency, nor an effect on
      the rate of habituation. PPI measures demonstrated robust alterations in
      sensorimotor gating. The PPI test (ISI of 0, 8, 40, 80, 120, or 4000 ms, 6-trial
      blocks, Latin-square) showed an attenuated response on peak ASR amplitude during
      the control trials (0 and 4000 ms ISI), but not on the PPI trials (8-120 ms ISI).
      Most striking was the rightward shift in ISI for maximal inhibition of the
      response (chi2(1)=4.7, p<or=0.03). There was no significant peak ASR latency
      effect during the control trials (<1 ms) of the PPI test, although there was the
      suggestion of a slowing of the response (4 ms, approximately 15%) across PPI
      trials. Collectively, the present data suggest that intrahippocampal injections
      of Tat have adverse effects on cognitive processing, as indexed by sensorimotor
      gating.

PMID- 16790269
TI  - Influence of breed and age on morphometry and depth of inseminating catheter
      penetration in the ewe cervix: a postmortem study.
AB  - A detailed examination of the cervical canal in the ewe was carried out. This
      analysis could be used to design new catheters for artificial insemination (AI)
      to achieve deeper cervical penetration and therefore better fertility results.
      Three hundred and sixty-five cervices from four sheep breeds (Churra, Assaf,
      Merino, Castellana) obtained postmortem were used. Cervix morphometry and depth
      of cervical penetration using two types of catheters were determined. A
      conventional straight catheter for ovine artificial insemination (IMV), and a
      bent catheter, ending in a stainless steel needle, 9 cm in length and with an 8
      mm tip bent 45 degrees , were used. The results showed that the morphometry of
      the cervix depends on breed and age of the ewe. The cervices of Churra breed were
      shorter and narrower, and had a higher number of folds than those of other
      breeds. Postmortem cervical penetration was deeper when the cervices were longer
      and wider, and with fewer folds (Merino and Castellana breeds). In ageing ewes,
      the cervix tended to become longer and wider, with loose folds. This decreased
      structural complexity and significantly improved cervical penetration. The bent
      catheter allowed significantly greater cervical penetration than the straight IMV
      one.

PMID- 16790268
TI  - Seminal plasma improves cryopreservation of Iberian red deer epididymal sperm.
AB  - We tested the protective action of seminal plasma on epididymal spermatozoa from
      Iberian red deer, especially considering cryopreservation, as a means for
      germplasm banking improvement. We obtained seminal plasma by centrifuging
      electroejaculated semen, and part of it was thermically inactivated (denatured
      plasma; 55 degrees C 30 min). Epididymal samples (always at 5 degrees C) were
      obtained from genitalia harvested after regulated hunting, and pooled for each
      assay (five in total). We tested three seminal plasma treatments (mixing seminal
      plasma with samples 2:1): no plasma, untreated plasma and denatured plasma; and
      four incubation treatments: 32 degrees C 15 min, 5 degrees C 15 min, 5 degrees C
      2h and 5 degrees C 6h. After each incubation, samples were diluted 1:1 with
      extender: Tes-Tris-Fructose, 10% egg yolk, 4% glycerol; equilibrated for 2h at 5
      degrees C, extended down to 10(8) spz./mL and frozen. Sperm quality was evaluated
      before 1:1 dilution, before freezing and after thawing the samples, assessing
      motility (CASA) and viability (percentage of viable and acrosome-intact
      spermatozoa; PI/PNA-FITC and fluorescent microscopy). Plasma treatment, both
      untreated and denatured, rendered higher viability before freezing and higher
      results for most parameters after thawing. The improvement was irrespective of
      incubation treatment, except for viability, which rendered slightly different
      results for untreated and denatured plasma. This may be due to the presence of
      thermolabile components. We still have to determine the underlying mechanisms
      involved in this protection. These results might help to improve the design of
      cryopreservation extenders for red deer epididymal sperm.

PMID- 16790270
TI  - Assessment of chromatin status (SCSA) in epididymal and ejaculated sperm in
      Iberian red deer, ram and domestic dog.
AB  - Abnormal chromatin condensation is not detected using classical techniques for
      sperm analysis. SCSA has demonstrated its usefulness in sperm chromatin analysis
      in several species (human, bull, stallion and boar). In this work, we studied
      sperm samples from red deer, ram and dog to analyze the differentiation of
      chromatin structure applying SCSA in epididymal and ejaculated spermatozoa.
      Epididymal samples were obtained from the caput, corpus and cauda by means of
      cuts, and ejaculated ones were obtained by electroejaculation (deer), artificial
      vagina (ram) and digital manipulation (dog). SCSA results suggested different
      critical points in sperm maturation (spermatozoa with loose chromatin to more
      condensed chromatin) among species: from corpus to cauda in ram and from caput to
      corpus in deer and dog. Moreover, we also detected differences in ruminants and
      dog, reflected in the appearance of SCSA plots. Indeed, ram and deer samples
      rendered two peaks within the sperm main population (sperm with condensed
      chromatin), whereas only one was detected in dog. Although some differences were
      observed between cauda and ejaculated samples, SCSA parameters indicated good
      chromatin condensation, making these samples suitable for germplasm banking. Some
      species-dependent modifications in the analysis of the results may be necessary
      to take full advantage of its analytical power.

PMID- 16790271
TI  - Polyacid-modified composite resins ("compomers") and their use in clinical
      dentistry.
AB  - OBJECTIVES: This paper describes the chemistry and properties of polyacid
      modified composite resins ("compomers") designed for use in clinical dentistry,
      and reviews the literature in this area. METHODS: Information has been obtained
      from over 50 published articles appearing in the dental and biomaterials
      literature, with studies being principally identified through MedLine. RESULTS:
      Published work shows that polyacid-modified composite resins constitute a
      discrete class of polymeric repair material for use in dentistry. Their
      distinction is that they contain hydrophilic components, and these cause water to
      be drawn into the material following cure. This triggers an acid-base reaction,
      and gives the materials certain clinically-desirable properties (fluoride
      release, buffering capability) that are also associated with glass-ionomer
      cements. The water uptake leads to a decline in certain, though not all, physical
      properties. However, clinical studies have shown these materials to perform
      acceptably in a variety of applications (Class I, Class II and Class V cavities,
      as fissure sealants and as orthodontic band cements), especially in children's
      teeth. CONCLUSIONS/SIGNIFICANCE: Polyacid-modified composite resins constitute a
      versatile class of dental repair material, whose bioactivity confers clinical
      advantages, and which are particularly useful in children's dentistry.

PMID- 16790272
TI  - Effect of silicon level on rate, quality and progression of bone healing within
      silicate-substituted porous hydroxyapatite scaffolds.
AB  - The osseous response to silicon (Si) level (0, 0.2, 0.4, 0.8 and 1.5 wt% Si)
      within 5 batches of matched porosity silicate-substituted hydroxyapatite (SA)
      scaffold was assessed by implantation of 4.6 mm diameter cylinders in the femoral
      intercondylar notch of New Zealand White rabbits for periods of 1, 3, 6 and 12
      weeks. Histological evaluation and histomorphometric quantification of bone
      ingrowth and mineral apposition rate (MAR) demonstrated the benefits to early (<1
      week) bone ingrowth and repair through incorporation of Si, at all levels, in
      porous hydroxyapatite (HA) lattices as compared to stoichiometric (0 wt% Si) HA.
      The group containing 0.8 wt% Si supported significantly more bone ingrowth than
      all other groups at 3 and 6 weeks (P<0.05), initially through its elevated MAR
      between weeks 1 and 2, which was significantly higher than that of all other Si
      containing groups (P<0.05). The level of silicate substitution also influenced
      the morphology and stability of the repair, with elevated levels of bone
      resorption and apposition apparent within other Si-containing groups at
      timepoints >3 weeks as compared to the 0 and 0.8 wt% Si groups. At 12 weeks, the
      net amount of bone ingrowth continued to rise in the 0, 0.8 and 1.5 wt% groups,
      apparently as a result of adaptive remodelling throughout the scaffold. Ingrowth
      levels remained highest in the 0.8 wt% Si group, was characterised by a dense
      trabecular morphology in the superficial region graduating to a more open network
      in the deep zone. These results highlight the sensitivity of healing response to
      Si level and suggest that an optimal response is obtained when SA is substituted
      with 0.8 wt% Si through its effect on the activity of both bone forming and bone
      resorbing cells.

PMID- 16790273
TI  - In vivo behavior of calcium phosphate scaffolds with four different pore sizes.
AB  - The goal of the present study was to assess the effect of macropore size on the
      in vivo behavior of ceramic scaffolds. For that purpose, beta-tricalcium
      phosphate (beta-TCP) cylinders with four different macropore sizes (150, 260,
      510, and 1220 microm) were implanted into drill hole defects in cancellous bone
      of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The
      scaffolds were evaluated for biocompatibility, and new bone formation was
      observed macroscopically, histologically and histomorphometrically.
      Histomorphometrical measurements were performed for the whole defect area and for
      the area subdivided into three concentric rings (outer, medial, and inner ring).
      All implants were tolerated very well as evidenced by the low amount of
      inflammatory cells and the absence of macroscopic signs of inflammation.
      Resorption proceeded fast since less than 5% ceramic remained at 24-week
      implantation. Hardly any effect of macropore size was observed on the in vivo
      response. Samples with an intermediate macropore size (510 microm) were resorbed
      significantly faster than samples with smaller macropore sizes (150 and 260
      microm). However, this fast resorption was associated with a lower bone content
      and a higher soft tissue content. At 12 and 24 weeks, the latter differences had
      disappeared. Bone was more abundant in the outer ring than in the rest of the
      blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at
      12 weeks.

PMID- 16790274
TI  - Role of limbic peptidergic circuits in regulation of arterial pressure, relevant
      to development of essential hypertension.
AB  - It is generally accepted that the essential hypertension (EH) is caused by
      interactions among congenital gene, multiple pathogenetic pressor factors, and
      disorder of physiologic depressor factors. The central nervous system may play a
      key role in the development of EH. The underlying mechanisms, however, are not
      well understood. Studies show that peptidergic transmitters in the limbic
      forebrain are involved in long-term regulation of arterial pressure and in the
      pathogenesis of EH. In the limbic forebrain there are peptidergic pressor and
      depressor circuits. The former includes corticotropin releasing factor-,
      substance P-, and angiotensin II-circuits; and the latter includes beta-endorphin
      and atrial natriuretic peptide-circuits. These circuits extensively interconnect
      and interact with each other. The altered functions of them may be the
      pathogenesis of EH. In this review, we focus on the roles of limbic peptidergic
      circuits in regulation of arterial pressure, relevant to the neurogenetic
      mechanisms in developing EH.

PMID- 16790275
TI  - Identification of a constitutively active mutant of JAK3 by retroviral expression
      screening.
AB  - To identify transforming genes in acute myeloid leukemia (AML) we here
      constructed a retroviral cDNA expression library from an AML patient, and then
      used this library to infect a mouse cell line 32Dcl3-mCAT. cDNA inserts of the
      cell clones which proliferated in the presence of granulocyte colony-stimulating
      factor were derived from JAK3 encoding a JAK3 mutant with a valine-to-alanine
      substitution at codon 674 and two additional amino acid substitutions. The
      transforming activity of JAK3(V674A) was confirmed by its introduction into
      32Dcl3-mCAT. Sequencing of the original JAK3 cDNA derived from the patient,
      however, failed to detect the V674A mutation.

PMID- 16790276
TI  - Penal managerialism from within: implications for theory and research.
AB  - Unlike the bulk of penological scholarship dealing with managerialist reforms,
      this article calls for greater theoretical and research attention to the often
      pernicious impact of managerialism on criminal justice professionals. Much in an
      ideal-typical fashion, light is shed on: the reasons why contemporary penal
      bureaucracies endeavor systematically to strip criminal justice work of its
      inherently affective nature; the structural forces that ensure control over
      officials; the processes by which those forces come into effect; and the human
      consequences of submission to totalitarian bureaucratic milieus. It is suggested
      that the heavy preoccupation of present-day penality with the predictability and
      calculability of outcomes entails the atomization of professionals and the
      dehumanization of their work. This is achieved through a kaleidoscope of direct
      and indirect mechanisms that naturalize and/or legitimate acquiescence.

PMID- 16790277
TI  - Novel peroxidase mimics: mu-Aqua manganese-Schiff base dimers.
AB  - The interaction of manganese(II) carboxylate salts [Mn(O(2)CR)(2), where
      R=ethane, pentane] with H(2)L(1) [N,N'-bis(3-methoxy-2-hydroxybenzaldehyde)-1,2
      phenylenediamine] and H(2)L(2) [N,N'-bis(3-ethoxy-2-hydroxybenzaldehyde)-1,2
      phenylenediamine] was studied. MnL(1)(O(2)CEt)(H(2)O) (1),
      MnL(1)(O(2)CPe(n))(H(2)O) (2), MnL(2)(O(2)CEt)(H(2)O)(2) (3) and
      MnL(2)(O(2)CPe(n))(H(2)O)(2) (4) were isolated and thoroughly characterised by
      elemental analysis, FAB mass spectrometry, infrared and (1)H NMR spectroscopy,
      magnetic susceptibility measurements, molar conductivities, and cyclic and normal
      pulse voltammetry. Compounds 1 and 2 were crystallographically characterised
      revealing a tetragonally elongated octahedral geometry for the manganese
      coordination sphere and also a dimeric nature through mu-aqua bridges. Complexes
      1-4 behave as efficient peroxidase mimics in the presence of the water-soluble
      trap ABTS, probably due to their ease to coordinate the substrate molecule. A
      correlation between rhombicity of the complexes and peroxidase activity has also
      been established.

PMID- 16790278
TI  - Mast cell function: regulation of degranulation by serine/threonine phosphatases.
AB  - Mast cells play both effector and modulatory roles in a range of allergic and
      immune responses. The principal function of these cells is the release of
      inflammatory mediators from mast cells by degranulation, which involves a complex
      interplay of signalling molecules. Understanding the molecular architecture
      underlying mast cell signalling has attracted renewed interest as the capacity
      for therapeutic intervention through controlling mast cell degranulation is now
      accepted as a viable proposition. The dynamic regulation of signalling by protein
      phosphorylation is a well-established phenomenon and many of the early events
      involved in mast cell activation are well understood. Less well understood
      however are the events further downstream of receptor activation that allow
      movement of granules through the cytoskeletal barrier and docking and fusion of
      granules with the plasma membrane. Whilst a potential role for the protein
      phosphatase family of signalling enzymes in mast cell function has been accepted
      for some time, the evidence has largely been derived from the use of broad
      specificity pharmacological inhibitors and results often depend upon the
      experimental conditions, leading to conflicting views. In this review, we present
      and discuss the pharmacological and recent molecular evidence that protein
      phosphatases, and in particular the protein phosphatase serine/threonine
      phosphatase type 2A (PP2A), have major regulatory roles to play and may be
      potential targets for the design of new therapeutic agents.

PMID- 16790279
TI  - Oxidative modification of low-density lipoprotein and immune regulation of
      atherosclerosis.
AB  - Oxidized low-density lipoprotein (oxLDL) is thought to promote atherosclerosis
      through complex inflammatory and immunologic mechanisms that lead to lipid
      dysregulation and foam cell formation. Recent findings suggested that oxLDL forms
      complexes with beta2-glycoprotein I (beta2GPI) and/or C-reactive protein (CRP) in
      the intima of atherosclerotic lesions. Autoantibodies against oxLDL/beta2GPI
      complexes occur in patients with systemic lupus erythematosus (SLE) and/or
      antiphospholipid syndrome (APS) and significantly correlate with arterial
      thrombosis. IgG autoantibodies having similar specificity emerged spontaneously
      in non-immunized NZWxBXSB F1 mice, an animal model of APS, and a monoclonal
      autoantibody (WB-CAL-1; IgG2a) against complexed beta2GPI (oxLDL/beta2GPI
      complexes) was derived from the same mice. WB-CAL-1 significantly increased the
      in vitro uptake of oxLDL/beta(2)GPI complexes by macrophages. This observation
      strongly suggests that such IgG autoantibodies are pro-atherogenic. In contrast,
      IgM anti-oxLDL natural antibodies found in the atherosclerosis-prone mice (ApoE(
      /-) and LDL-R(-/-) mice) have been proposed to be anti-atherogenic (protective).
      The presence of IgG anti-oxLDL antibodies in humans has been documented in many
      publications but their exact clinical significance remains unclear. In this
      article, we review recent progress in our understanding of the mechanisms
      involved in oxidation of LDL, formation of oxLDL complexes, and antibody mediated
      immune regulation of atherogenesis.

PMID- 16790280
TI  - Immune responses to Staphylococcus aureus and Psoroptes ovis in sheep infected
      with P. ovis--the sheep scab mite.
AB  - In sheep, lesions caused by Psoroptes ovis, the sheep scab mite, may become
      colonized by Staphylococcus aureus. The present study compares clinical signs,
      lesional area and the immune response to P. ovis and S. aureus in P. ovis
      infested sheep with and without secondary S. aureus infection. No differences
      were detected in the clinical signs or lesional areas in the S. aureus-positive
      and -negative sheep. However, 6 weeks after infestation an IgG but not IgE
      isotype antibody response to S. aureus was detected in the S. aureus-positive but
      not the S. aureus-negative group of sheep. This response targeted S. aureus
      antigens with molecular weights of approximately 36, 38, 50 and 65 kDa. In
      addition, 6 weeks after infestation an IgE response to P. ovis was detected in
      the S. aureus-positive but not the S. aureus-negative group of sheep.

PMID- 16790281
TI  - Potent inhibition of HIV-1 gene expression and TAT-mediated apoptosis in human T
      cells by novel mono- and multitarget anti-TAT/Rev/Env ribozymes and a general
      purpose RNA-cleaving DNA-enzyme.
AB  - One of the hallmarks of progression of HIV-1/AIDS is the rapid depletion of CD4+T
      cells that is known to occur at the late stages of the disease when usually X4
      tropic HIV-1 predominates. Besides direct killing of T lymphocytes, HIV-1
      infection leads to extensive apoptosis of naive/uninfected bystander T cells,
      which is predominantly mediated by HIV-1 TAT protein. Therefore, reduction of HIV
      1 TAT protein is likely to reduce substantially the pathogenesis associated with
      HIV-1 infection. We designed two non-GUX hammerhead ribozymes (Rzs) and a Di-Rz
      by placing them in direct tandem. These were targeted against the most conserved
      second exon of HIV-1 TAT/Rev/Env region. Although very impressive in vitro
      cleavage of the target RNA by the two hammerhead Rzs was obtained under standard
      conditions of cleavage, only one of them was active under simulated physiological
      conditions. Sequence-specific cleavage by the Di-Rz was most efficient under
      standard conditions. Cleavage reactions carried out under simulated physiological
      conditions by the Di-Rz, however, indicated that both mono-Rzs were functional.
      We also assembled a 10-23 catalytic motif containing general purpose RNA-cleaving
      DNA-enzyme (Dz) against the same region, which cleaved the target RNA very
      efficiently. Both Rzs and Dz showed not only potent inhibition of HIV-1 gene
      expression but also showed remarkable protection against HIV-1 TAT protein
      mediated apoptosis in Jurkat T cells. Possible implications of these findings are
      discussed.

PMID- 16790282
TI  - Visual search for moving and stationary items in chimpanzees (Pan troglodytes)
      and humans (Homo sapiens).
AB  - Four visual search experiments were conducted using human and chimpanzee subjects
      to investigate attentional processing of movement, and perceptual organization
      based on movement of items. In the first experiment, subjects performed visual
      searches for a moving target among stationary items, and for a stationary target
      among moving items. Subjects of both species displayed an advantage in detecting
      the moving item compared to the stationary one, suggesting the priority of
      movement in the attentional processing. A second experiment assessed the effect
      of the coherent movement of items in the search for a stationary target.
      Facilitative effects of motion coherence were observed only in the performance of
      human subjects. In the third and fourth experiments, the effect of coherent
      movement of the reference frame on the search for moving and stationary targets
      was tested. Related target movements significantly influenced the search
      performance of both species. The results of the second, third, and fourth
      experiments suggest that perceptual organization based on coherent movements is
      partially shared by chimpanzees and humans, and is more highly developed in
      humans.

PMID- 16790283
TI  - Regulation of iron acquisition and iron distribution in mammals.
AB  - Both cellular iron deficiency and excess have adverse consequences. To maintain
      iron homeostasis, complex mechanisms have evolved to regulate cellular and
      extracellular iron concentrations. Extracellular iron concentrations are
      controlled by a peptide hormone hepcidin, which inhibits the supply of iron into
      plasma. Hepcidin acts by binding to and inducing the degradation of the cellular
      iron exporter, ferroportin, found in sites of major iron flows: duodenal
      enterocytes involved in iron absorption, macrophages that recycle iron from
      senescent erythrocytes, and hepatocytes that store iron. Hepcidin synthesis is in
      turn controlled by iron concentrations, hypoxia, anemia and inflammatory
      cytokines. The molecular mechanisms that regulate hepcidin production are only
      beginning to be understood, but its dysregulation is involved in the pathogenesis
      of a spectrum of iron disorders. Deficiency of hepcidin is the unifying cause of
      hereditary hemochromatoses, and excessive cytokine-stimulated hepcidin production
      causes hypoferremia and contributes to anemia of inflammation.

PMID- 16790284
TI  - Septum hematoma: a complication of retrograde wiring in chronic total occlusion.
AB  - In spite of the remarkable technological innovation and improved outcomes with
      percutaneous coronary intervention (PCI), chronically total occlusion in coronary
      arteries (CTO) remains a formidable challenge for coronary interventionalist.
      Recently Japanese interventionists have proposed a retrograde wiring technique
      which provides another way to resolve such difficulties. The retrograde wire in
      the distal CTO vessel can then be used as a clear landmark in the distal true
      lumen, facilitating antegrade wiring and possibly increasing the success rate of
      CTO-PCI. Reported here is a patient who experienced retrograde wire technique but
      suffered from a complication with septum hematoma and myocardial infarction. The
      patient had a complete recovery of chest symptoms and resolution of septum
      hematoma in 1 month. Retrograde wire manipulation should be used as a last resort
      and via a large collateral vessel in the treatment of CTO.

PMID- 16790285
TI  - Performance evaluation of a low conductive growth medium (LCGM) for growth of
      healthy and stressed Listeria monocytogenes and other common bacterial species.
AB  - The performance of a low conductive growth medium (LCGM) (conductivity of <1300
      microS) was evaluated for its ability to support growth of food borne bacterial
      pathogens including Listeria monocytogenes and to determine the expression of the
      two key virulence proteins in L. monocytogenes for possible applications in an
      impedance-based microfluidic biochip detection platform. Growth of Listeria was
      monitored spectrophotometrically and the lag phase, generation time, growth rate
      and maximum population density were determined using the Gompertz equation. LCGM
      had a lag phase of 2.3 h and showed a higher cell density compared to Luria
      Bertini (LB) broth. Length of lag phase was highly dependent on initial inoculum
      concentrations. The changes in conductivity with respect to growth in the low
      conductive medium were monitored using a conductivity probe. L. monocytogenes
      growth could be detected within 2 h (0.1 mS) in LCGM and within 6 h in LB. The
      performance of the media was also evaluated for the recovery of Listeria cells
      exposed to various stresses as 42 degrees C for 1, 2 or 6 h, an osmotic stress in
      10.5% NaCl, an acidic stress at pH 2, 3 or 5 and a combined stress of 10.5% NaCl,
      pH 5 and 1 h exposure at 42 degrees C. The recovery rate was comparable with that
      of Tryptic soy broth containing yeast extract (TSBYE). L. monocytogenes in LCGM
      supported the expression of two key virulence markers, actin polymerization
      protein (ActA) and internalin B (InlB), which could be detected using specific
      antibodies. In general LCGM also supported the growth of several other bacterial
      species suggesting its implication in microbial quality monitoring of products.
      In conclusion, LCGM is a sensitive low conductive medium that supports the growth
      as well as the expression of virulence markers for potential applications in
      sensitive detection of L. monocytogenes or other food borne pathogens in
      impedance-based sensor platform.

PMID- 16790286
TI  - A new method for RAPD primers selection based on primer bias in nucleotide
      sequence data.
AB  - Sequence analysis has proved that decamer nucleotides, used as primers of RAPD
      (random amplified polymorphic DNA), differ with each other greatly in number of
      annealing sites in the Arabidopsis thaliana genome. It is called the 'primer
      bias' by the authors. The biased primers produce a highly variable number of
      amplicons by polymerase chain reaction (PCR). The number of amplicons is proved
      to correlate with the number of annealing sites. Therefore, a statistical method
      is proposed for selecting efficient primers based on the primer bias in the
      genomic sequence. The method was tested by experiment in A. thaliana genome, and
      the results demonstrate that the method outperforms routine methods and can
      substantially increase the efficiency of RAPD methodologies. We also proved that
      the expressed sequence tags (ESTs) show a highly coincident bias pattern with
      that of the whole genomic sequence, and can therefore be used to assess
      efficiencies of primers for species whose genomic sequence data are currently
      unknown.

PMID- 16790287
TI  - Real-time quantitative LAMP (loop-mediated isothermal amplification of DNA) as a
      simple method for monitoring ammonia-oxidizing bacteria.
AB  - Loop-mediated isothermal amplification (LAMP) of DNA is a novel technique for the
      amplification of DNA under isothermal conditions. For the first time, we applied
      this method to develop a simple and quantitative monitoring method for
      environmental microorganisms targeting amoA gene in ammonia-oxidizing bacteria.
      Quantitative analysis was performed first by measuring fluorescence derived from
      an intercalation dye using a real-time thermal cycler, and then by measuring the
      turbidity of the reaction solution using a real-time turbidimeter. As a result,
      it was possible to quantify the initial amoA DNA concentration from an
      environment with a sensitivity down to 10(2) DNA copies of target DNA and a
      dynamic range of 7-9 orders in magnitude. Background DNA from nontargeted
      bacteria (Pseudomonas denitrificans) that does not encode amoA gene did not
      affect the quantitative capability of LAMP. Over results suggested that the real
      time LAMP is effective for monitoring microorganisms and their gene expression in
      environments.

PMID- 16790288
TI  - Gene reconstitution using high efficiency homologous recombination between a
      bacteriophage fd and a plasmid.
AB  - Highly efficient intermolecular crossing-over was observed occurring between
      regions of limited homology in a fd filamentous phage and a plasmid. These
      extraneous regions corresponded to two overlapping fragments of the beta
      lactamase gene. Gene reconstitution through homologous recombination of these
      regions yielded a highly ampicillin-resistant phenotype in Escherichia coli while
      co-expression of the enzyme fragments afforded low and thermosensitive activity.
      The recombination rates were between two and three orders of magnitude higher
      than that reported between plasmids using a similar assay. The fd-plasmid
      cointegrate was detected in recombined bacteria, as was its encapsidation into
      phage particles and subsequent transduction. A 100-fold reduction in the
      recombination rate was observed in a recA mutant strain even though crossing-over
      was still efficient. This gene reconstitution strategy is generally applicable to
      phage display technology and provides an easy way for constructing large
      combinatorial libraries of mutants.

PMID- 16790289
TI  - The short consensus repeats 1 and 2, not the cytoplasmic domain, of human CD46
      are crucial for infection of subgroup B adenovirus serotype 35.
AB  - Human CD46 (membrane cofactor protein) has recently been identified to be an
      attachment receptor for subgroup B adenoviruses (Ads); however, the precise
      interaction between human CD46 and subgroup B Ads are just beginning to be
      understood. In this study, to characterize the interaction between human CD46 and
      subgroup B Ads, varieties of mutant CD46 were tested for their ability to act as
      a receptor for Ad serotype 35 (Ad35), which belongs to subgroup B. In addition,
      we determined Ad35 vector-mediated transgene expression and cellular uptake of
      Ad35 vectors in the presence of a set of anti-CD46 antibodies. Our data
      demonstrated that the short consensus repeats (SCRs) 1 and 2 in human CD46 are
      important for interaction with Ad35, whereas the cytoplasmic domain of human CD46
      was found not to be required for the function as an Ad35 receptor. Rather, a
      complete deletion of the cytoplasmic domain of human CD46 increased the
      transduction efficiencies of Ad35 vectors. This information should help in
      elucidation of the mechanism of subgroup B Ad infection, as well in the
      improvement of the subgroup B Ad vectors.

PMID- 16790290
TI  - Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective.
AB  - Antioxidants are emerging as prophylactic and therapeutic agents. These are the
      agents, which scavenge free radicals otherwise reactive oxygen species and
      prevent the damage caused by them. Free radicals have been associated with
      pathogenesis of various disorders like cancer, diabetes, cardiovascular diseases,
      autoimmune diseases, neurodegenerative disorders and are implicated in aging.
      Several antioxidants like SOD, CAT, epigallocatechin-3-O-gallate, lycopene,
      ellagic acid, coenzyme Q10, indole-3-carbinol, genistein, quercetin, vitamin C
      and vitamin E have been found to be pharmacologically active as prophylactic and
      therapeutic agents for above mentioned diseases. Antioxidants are part of diet
      but their bioavailability through dietary supplementation depends on several
      factors. This major drawback of dietary agents may be due to one or many of the
      several factors like poor solubility, inefficient permeability, instability due
      to storage of food, first pass effect and GI degradation. Conventional dosage
      forms may not result in efficient formulation owing to their poor
      biopharmaceutical properties. Principles of novel drug delivery systems need to
      be applied to significantly improve the performance of antioxidants. Novel drug
      delivery systems (NDDS) would also help in delivery of these antioxidants by oral
      route, as this route is of prime importance when antioxidants are intended for
      prophylactic purpose. Implication of NDDS for the delivery of antioxidants is
      largely governed by physicochemical characteristics, biopharmaceutical properties
      and pharmacokinetic parameters of the antioxidant to be formulated. Recently,
      chemical modifications, coupling agents, liposomes, microparticles, nanoparticles
      and gel-based systems have been explored for the delivery of these difficult to
      deliver molecules. Results from several studies conducted across the globe are
      positive and provided us with new anticipation for the improvement of human
      healthcare.

PMID- 16790291
TI  - Bone tissue engineering by gene delivery.
AB  - Recombinant human bone morphogenetic protein-2 and -7 were recently granted
      United States Food and Drug Administration approval for select clinical
      applications in bone repair. While significant progress has been made in the
      delivery of recombinant osteogenic factor to promote bone healing, the short half
      life and instability of the protein requires the delivery of milligram quantities
      of factor or multiple dosages. The potential of gene therapy for bone
      regeneration is the delivery of physiological levels of therapeutic protein using
      natural cellular mechanisms. Experimental investigations have demonstrated this
      approach uses lower dosages of factor to yield bone healing equivalent to that
      achieved via the administration of recombinant factor or use of bone grafts. The
      current states of gene delivery for bone tissue engineering applications and
      challenges to be met are presented in this review. Over the past couple of years,
      studies have continued to examine the delivery of the osteogenic factor bone
      morphogenetic protein using gene therapies. The importance of angiogenesis to
      bone formation has prompted the development of vascular endothelial growth factor
      gene expression systems for bone regeneration. Viral vectors, in combination with
      allograft bone, have been investigated to improve existing surgical care. Newly
      constructed vectors with reduced immunogenicity and regulated gene expression
      systems provide a greater degree of control over the timing and level of gene
      expression. Several advances have allowed bone tissue engineering by gene
      delivery to advance beyond serving as a potential treatment for isolated bone
      defects and fractures to a gene therapy approach for the treatment of genetic
      based bone diseases, such as osteogenesis imperfecta.

PMID- 16790292
TI  - Spontaneous remission of small cell lung cancer: a case report and review in the
      literature.
AB  - Spontaneous remission (SR) of cancer, especially of lung tumor, is a rare
      biological event. Only seven cases in which small cell lung cancer (SCLC)
      regressed spontaneously had been previously reported. We report here a rare case
      of complete SR of SCLC in an 86-year-old man. Paraneoplastic sensory neuronopathy
      (PSN) is a rare syndrome, which is associated with malignancy such as SCLC and
      starts with dysesthetic pain and numbness in the distal extremities, then
      spreading all four limbs and trunk causing severe sensory ataxia. In the previous
      reports, SR of SCLC is suggested to result from surgical trauma or PSN, which may
      be able to enhance anti-tumoral immunity. Our report is the case of SR of SCLC,
      without any therapies nor any invasive examinations. Although the reason of SR of
      SCLC in the present case is unknown, PSN could be one of the diagnosis by
      exclusion.

PMID- 16790293
TI  - Rational drug sequencing of paclitaxel, gemcitabine and carboplatin in patients
      with untreated stage IV and select stage IIIB non-small cell lung cancer.
AB  - INTRODUCTION: To conduct a phase II study evaluating the efficacy of rationally
      sequenced paclitaxel, gemcitabine, and carboplatin in patients with stage IV or
      select stage IIIB non-small cell lung cancer (NSCLC). METHODS: Patients with
      select stages IIIB (pleural effusion) and IV NSCLC with an ECOG performance
      status of 0-1 and no prior chemotherapy for their disease were eligible to
      participate. Treatment was delivered as follows: paclitaxel at 70 mg/m2 followed
      by gemcitabine at 300 mg/m2 on day 1, with carboplatin (AUC 5) on day 2 of a 28
      day cycle. Response was assessed after every two cycles of therapy. The primary
      endpoint of this trial was response rate, with secondary endpoints of time to
      progression and 1 year overall survival. RESULTS: Twenty patients were enrolled
      on protocol, one of whom never received chemotherapy. The median number of cycles
      delivered was 3 (range 0-8). A partial response rate of 42% (8/19; 95% CI: 20
      67%) and a stable disease rate of 11% (2/19; 95% CI: 1-33%) were observed. The
      median overall survival time was 9.6 months (95% CI: 4.6-16.6), with a 1 year
      overall survival rate of 42.1% (95% CI: 24.9-71.3%). Eight patients (42%) stopped
      treatment due to toxicity. CONCLUSION: Paclitaxel followed by gemcitabine and
      then carboplatin is an active, albeit complex, regimen in the treatment of
      patients with advanced NSCLC with insufficient advantage to justify continuation
      of this regimen.

PMID- 16790294
TI  - Monomeric red fluorescent protein variants used for imaging studies in different
      species.
AB  - Fluorescent proteins have proven to be excellent tools for live-cell imaging
      studies. In addition to green fluorescent protein (GFP) and its variants, recent
      progress was achieved in the development of monomeric red fluorescent proteins
      (mRFPs) that show improved properties in respect to maturation and intracellular
      fluorescence. mRFPmars, a red fluorescent protein designed especially for the use
      in Dictyostelium, has been employed to tag different proteins for live-cell
      investigations in Dictyostelium. mRFPruby, which differs in sequence from
      mRFPmars in four amino acids, has a codon usage optimised for the application in
      mammalian cells. Here, we show that both mRFP variants can also be applied for
      localisation studies in other organisms. mRFPmars was expressed in Hydra and
      fused to the Bcl-2 family protein Bax. mRFPruby in combination with histone 2B
      was expressed in Drosophila S2 cells to monitor mitosis. Using mouse cell lines,
      mRFPruby fused to beta-actin was assayed with high spatial resolution to study
      details of actin cytoskeleton dynamics. In addition, we demonstrate that both
      mRFP variants are also suitable for dual-colour microscopy in the different
      species.

PMID- 16790295
TI  - Components of the peptidome and transcriptome persist in lin wa pi: the dried
      skin of the Heilongjiang brown frog (Rana amurensis) as used in traditional
      Chinese medicine.
AB  - Although the ancient practice of traditional Chinese medicine (TCM) utilizes
      predominantly herbal ingredients, many of which are now the subject of intense
      scientific scrutiny, significant quantities of animal tissue-derived materials
      are also employed. Here we have used contemporary molecular techniques to study
      the material known as lin wa pi, the dried skin of the Heilongjiang brown frog,
      Rana amurensis, that is used commonly as an ingredient of many medicines, as a
      general tonic and as a topical antimicrobial/wound dressing. Using a simple
      technology that has been developed and validated over several years, we have
      demonstrated that components of both the skin granular gland peptidome and
      transcriptome persist in this material. Interrogation of the cDNA library
      constructed from the dried skin by entrapment and amplification of polyadenylated
      mRNA, using a "shotgun" primer approach and 3'-RACE, resulted in the cloning of
      cDNAs encoding the precursors of five putative antimicrobial peptides. Two
      (ranatuerin-2AMa and ranatuerin-2AMb) were obvious homologs of a previously
      described frog skin peptide family, whereas the remaining three were of
      sufficient structural novelty to be named amurins 1-3. Mature peptides were each
      identified in reverse phase HPLC fractions of boiling water extracts of skin and
      their structures confirmed by MS/MS fragmentation sequencing. Components of
      traditional Chinese medicines of animal tissue origin may thus contain
      biologically active peptides that survive the preparation procedures and that may
      contribute to therapeutic efficacy.

PMID- 16790296
TI  - Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent
      rats.
AB  - Previous studies indicate that long-term dietary supplementation with arachidonic
      acid (AA) in 20-month-old rats (OA) effectively restores performance in a memory
      task and the induction of long-term potentiation in the hippocampus to the level
      of young control animals (YC). The present study examined protein mobility using
      the live cell imaging technique "Fluorescent Recovery After Photobleaching
      (FRAP)" in YC, old control (OC) and OA neurons in hippocampal slice preparations.
      Three measures; mobile fraction (M(f)), diffusion constant (D) and time constant
      (tau), were estimated among YC, OC and OA. Each of these parameters was
      significantly different between OC and YC, suggesting that membrane fluidity is
      lower in OC than in YC. In contrast, D and tau were comparable in OA and YC,
      indicating that hippocampal neuronal membranes supplemented with AA were more
      fluid than those in OC, whereas the fraction of diffusible protein in the
      bleached region remained smaller than in YC. Long-term administration of AA to
      senescent rats might help to preserve membrane fluidity and maintain hippocampal
      plasticity.

PMID- 16790297
TI  - Design of beta-carboline derivatives as DNA-targeting antitumor agents.
AB  - This research studied the structure-activity relationship of beta-carboline
      derivatives as antitumor agents, in which 41 synthesized compounds and their
      cytotoxicity to tumor and normal cell lines were assayed. It was proved that
      substituent in position-9 of the beta-carboline ring could reinforce the DNA
      intercalating ability and consequently cytotoxicity to tumor cell lines, and the
      amidation of amino group at the end of the DNA targeting side chain in position-3
      could cripple the DNA intercalating activity of these compounds, which
      resultingly initiated the cytotoxic selectivity to tumor cell lines rather than
      to normal ones. Furthermore, the S and G2-M arrest induced by these compounds
      confirmed that they could target DNA and lead to DNA destructions in Hela cells.
      In short, this study may provide a framework to design a novel antitumor drug
      that could surpass Adriamycin.

PMID- 16790298
TI  - [Chronic gingivostomatitis].

PMID- 16790299
TI  - [Infectious or inflammatory aortitis? One case report].
AB  - INTRODUCTION: The infectious or inflammatory nature of an aortitis is difficult
      to assert because the microbiological results are often negative. The development
      of an aneurysm under treatment is rare, but requires a change in the therapeutic
      strategy and the etiologic diagnosis needs to be discussed again. EXEGESIS: We
      report the case of a 69-year-old woman treated by corticotherapy for an aortitis
      thought to be inflammatory, who required emergency surgery when a dissected
      aneurysm appeared. The peroperative samples were positive to Streptococcus
      pneumoniae using polymerase chain reaction and allowed a change of the diagnosis.
      The patient evolved favorably under antibiotic therapy. CONCLUSION: The decision
      to treat an aortitis by corticotherapy must be made with caution even if the
      microbiological tests are negative.

PMID- 16790300
TI  - [Ambroxol-induced immune hemolytic anemia].
AB  - INTRODUCTION: Drug-induced immune hemolytic anemia is a rare cause of hemolytic
      anemia. CASE RECORD: A 68-year-old male patient developed an acute intravascular
      hemolysis with acute renal failure. Common causes of hemolysis were ruled out and
      the patient rapidly improved. An immune mechanism was confirmed by the positivity
      of the direct antiglobulin test with anti-IgA in the presence of ambroxol only,
      one of the drug the patient had received during 6 days before hospitalization.
      DISCUSSION: To our knowledge, this is the first report of ambroxol-induced immune
      hemolytic anemia. This case also underlined that the direct antiglobulin test
      should also be performed with anti-IgA to rule out any false negative.

PMID- 16790301
TI  - Lights, camera, education! The potentials of forum theatre in a learning
      disability nursing program.
AB  - Learning disability nurse education, with a current emphasis on inclusive
      practice and a history of listening to the person with the disability, is well
      placed to take advantage of more 'experimental' forms of classroom teaching. In
      this article we argue for the use of forum theatre as a method of addressing
      topics from practice within an educational setting. Based on our emergent and
      exploratory work with students we detail at length the theoretical background
      that supports such an approach and contextualise the issues with reference to a
      short piece of drama we have used successfully with different student groups. We
      feel that the success of this method is due to the involvement of students in
      directing their own education as well as the inclusion of individuals labelled
      with learning disability as an integral part of the process.

PMID- 16790302
TI  - Assessing the introduction of universal varicella vaccination in the Netherlands.
AB  - Although varicella is seen as a benign disease in the Netherlands, about 40,000
      visits to a general practitioner (GP) are made, over 200 hospital admission
      occur, and 2.3 persons die on average each year. Most of this burden of disease
      can be prevented by universal varicella childhood vaccination. Ten years after
      the introduction of the single-shot, single-component varicella childhood
      vaccination in the USA, a major reduction in hospitalization, mortality, and
      burden of disease has been reported. Using our recently vaccine evaluation model
      for the introduction of a new vaccine in our national immunization program, we
      have analyzed the feasibility of universal varicella vaccination by replacing the
      measles-mumps-rubella (MMR) vaccine with a measles-mumps-rubella-varicella (MMRV)
      vaccine. After structuring and reviewing the available data, two major points of
      uncertainty remain: (1) the influence of universal childhood vaccination on the
      incidence of zoster later in life; (2) the cost-effectiveness ratio for the Dutch
      situation. Despite these uncertainties it is clear that universal childhood
      vaccination will prevent most of the varicella related GP-visits,
      hospitalizations, and deaths.

PMID- 16790303
TI  - Passive immunotherapy of Bacillus anthracis pulmonary infection in mice with
      antisera produced by DNA immunization.
AB  - Because of the high failure rate of antibiotic treatment in patients with anthrax
      there is a need for additional therapies such as passive immunization with
      therapeutic antibodies. In this study, we used codon-optimized plasmid DNAs (DNA
      vaccines) encoding Bacillus anthracis protective antigen (PA) to immunize rabbits
      for producing anti-anthrax antibodies for use in passive immunotherapy. The
      antisera generated with these DNA vaccines were of high titer as measured by
      ELISA. The antisera were also able to protect J774 macrophage cells by
      neutralizing the cytotoxic effect of exogenously added anthrax lethal toxin, and
      of the toxin released by B. anthracis (Sterne strain) spores following infection.
      In addition, the antisera passively protected mice against pulmonary challenge
      with an approximate 50 LD50 dose of B. anthracis (Sterne strain) spores. The
      protection in mice was obtained when the antiserum was given 1h before or 1h
      after challenge. We further demonstrated that IgG and F(ab')2 components purified
      from anti-PA rabbit hyperimmune sera retained similar levels of neutralizing
      activities against both exogenously added B. anthracis lethal toxin and toxin
      produced by B. anthracis (Sterne strain) spores. The high titer antisera we
      produced will enable an immunization strategy to supplement antibiotic therapy
      for improving the survival of patients with anthrax.

PMID- 16790304
TI  - The effect of an impulsive knee valgus moment on in vitro relative ACL strain
      during a simulated jump landing.
AB  - BACKGROUND: We tested the hypothesis that impulsive compression, flexion and
      valgus knee moment loading during a simulated one-footed jump landing will
      significantly increase the peak relative strain in the anteromedial region of the
      anterior cruciate ligament compared with loading without the valgus moment.
      METHODS: Ten cadaveric knees [mean (SD) age: 67.9 (7.6) years; 5 males; 5
      females] were mounted into a custom fixture to simulate a lower extremity impact
      loading of approximately 1600 N. Triaxial load cells monitored the 3D tibial and
      femoral impulsive force and moments at 2000 Hz, while 3D tibiofemoral kinematics
      were measured at 400 Hz. Pre-impact quadriceps, hamstring and gastrocnemius
      muscle forces were simulated using pretensioned steel cables. A differential
      variable reluctance transducer measured the relative strain in the anteromedial
      aspect of the anterior cruciate ligament. With the knee initially in 25 degrees
      flexion, 10 trials were conducted with the impulsive force directed 4 cm
      posterior to the knee joint center in the sagittal plane ("neutral" loading) to
      cause a flexion moment, 10 trials were conducted under a similar loading, but
      with the force directed 15 degrees lateral to the knee sagittal plane ("valgus"
      loading), and the 10 neutral loading trials were then repeated. A non-parametric
      Wilcoxon signed rank test was used to test the hypothesis using a P<0.05
      significance level. FINDINGS: The peak normalized anterior cruciate ligament
      strain was 30% larger for the impulsive compression loading in valgus and flexion
      compared with an impulsive compression loading in isolated flexion (P<0.05).
      INTERPRETATION: Minimizing the abduction loading of the knee during a jump
      landing should help reduce anterior cruciate ligament strain during that
      maneuver.

PMID- 16790306
TI  - DSM-IV and dangerous and severe personality disorder--an essay.
AB  - In this essay some reflections are offered on the nature of psychiatric
      classification, on how these diagnostic categories have evolved in the Diagnostic
      and Statistical Manuals of Mental Disorders (DSM) system and on the development
      of services based on them. These are described, and then analysed from the
      perspective of the sociology of knowledge, using 'personality disorder' as an
      example. Conditions that underlie the stabilisation of such categories, and the
      policy and political consequences of basing services on them, are reviewed.

PMID- 16790305
TI  - The significance for decision-making of information that is not exchanged by
      patients and health professionals during consultations.
AB  - Information exchange between patients and health professionals is fundamental to
      achieving patient participation in decision-making and shared decision-making is
      said to require the exchange of "all information relevant to decision-making".
      This paper reports on a qualitative investigation of instances in which
      information that was potentially relevant to decision-making was not exchanged in
      consultations. Consultations from 5 diverse clinical areas in the UK were video
      recorded and the health professionals and patients involved were interviewed
      separately before and after their consultations. This analysis is based on cases
      involving 20 patients. It draws on data from their 26-recorded consultations and
      from the 137 associated interviews. Several strategies were used to identify
      instances in which patients and/or health professionals did not disclose
      information that was potentially relevant to decision-making. Analysis focussed
      on the types of information not disclosed, the reasons that health professionals
      and patients gave for non-disclosure, and the apparent or potential significance
      of the non-disclosure. We identified 34 instances of non-disclosure of
      information relating to the patient's problem and 52 instances of non-disclosure
      of information relating to treatment or management options. The types of
      information not disclosed were diverse and the reasons given for non-disclosure
      varied. Some, but not all, instances of non-disclosure had negative implications
      for the quality of decision-making and/or the patient's healthcare experience.
      Our findings have implications for future attempts to examine information
      exchange in consultations-whether for research or for professional assessment
      purposes. In particular, they highlight the importance of appraising instances of
      non-disclosure of information in context and of recognising the limitations of
      approaches that rely on single consultations and/or single perspectives for
      assessments of information exchange.

PMID- 16790307
TI  - Dilemmas of talking about lifestyle changes among couples coping with a cardiac
      event.
AB  - Persons who have experienced a myocardial infarction (MI) and/or coronary artery
      bypass graft (CABG) surgery may benefit from a low-fat diet, regular exercise,
      smoking cessation, and stress management. Yet many patients do not make these
      changes. A spouse or partner's attempts at support may facilitate or interfere
      with patient behavior change. The present study explores dilemmas that may arise
      when couples talk about lifestyle changes following one person's MI or CABG. In
      interviews carried out in Urbana-Champaign, Illinois, and surrounding communities
      with 25 patients and 16 partners we found communicating support for lifestyle
      change may be interpreted as undesired control or criticism. The caring conveyed
      by talking may be viewed positively but can also threaten patient autonomy and
      entrap partners in unwanted expectations and obligations. Finally, lifestyle
      change conversations may reflect empowered patients collaborating with partners
      to take control of health but can also serve as potent reminders of loss. These
      multiple, potentially conflicting meanings give an account for why talking with a
      partner does not always facilitate patient lifestyle change. Understanding these
      dilemmas also suggests practical implications for helping patients and partners.

PMID- 16790308
TI  - The influence of economic development level, household wealth and maternal
      education on child health in the developing world.
AB  - This study estimates the relative importance to child health (indicated by weight
      and height for age) of economic development level [gross domestic product (GDP)
      converted to international dollars using purchasing power parity (PPP) rates: GDP
      PPP], household wealth and maternal education and examines the modifying
      influence of national contexts on these estimates. It uses information collected
      from mothers aged 15-49-years participating in Demographic Health Surveys (DHS)
      conducted in 42 developing countries. In multilevel regression models, the three
      study variables exhibited strong independent associations with child health: GDP
      PPP accounted for the largest amount of unique variation, followed by maternal
      education and household wealth. There was also substantial overlap (shared
      variance) between maternal education and the other two study variables. The
      regressions of child health on household wealth and maternal education exhibited
      substantial cross-national variation in both strength and form of association.
      Although higher education levels were associated with disproportionately greater
      returns to child health, the pattern for household wealth was erratic: in many
      countries there were diminishing returns to child health at higher levels of
      household wealth. We conclude that there are inextricable links among different
      strategies for improving child health and that policy planners, associating
      benefits with these strategies, must take into account the strong moderating
      impact of national context.

PMID- 16790309
TI  - Gendering the migraine market: do representations of illness matter?
AB  - Migraine is a common, debilitating and costly disorder. Yet help-seeking for and
      rates of diagnosis of migraine are low. Drawing on ethnographic observations of
      pharmaceutical marketing practices at professional headache conferences and a
      content analysis of migraine advertising, principally in the USA, this paper
      demonstrates: (1) that the pharmaceutical industry directs its marketing of
      migraine medication to women; and (2) as part of this strategy, pharmaceutical
      advertisements portray women as the prototypical migraine sufferer, through
      representations that elicit hegemonic femininity. This strategy creates the
      impression that migraine is a "women's disorder", which, in turn, exacerbates
      gender bias in help seeking and diagnosis of migraine and reifies presumptions
      about the epidemiology of the disorder. I conclude that these pharmaceutical
      marketing practices have a paradoxical effect: even as they educate and raise
      awareness about migraine, they also create barriers to help seeking and
      diagnosis.

PMID- 16790310
TI  - From bench to bedside? Biomedical scientists' expectations of stem cell science
      as a future therapy for diabetes.
AB  - The movement of scientific research from the bench to the bedside is becoming an
      increasingly important aspect of modern 'biomedical societies'. There is,
      however, currently a dearth of social science research on the interaction between
      the laboratory and the clinic. The recent upsurge in global funding for stem cell
      research is largely premised on the promise of translating scientific
      understanding of stem cells into regenerative medicine. In this paper, we report
      on the views of biomedical scientists based in the United Kingdom who are
      involved in human embryonic stem cell research in the field of diabetes. We
      explore their views on the prospects and problems of translational research in
      the field of stem cell science. We discuss two main themes: institutional
      influences on interactions between scientists and clinicians, and stem cell
      science itself as the major barrier to therapies. We frame our discussion within
      the emerging literature of the sociology of expectations.

PMID- 16790311
TI  - Evidence for a functional genetic polymorphism of the human thiosulfate
      sulfurtransferase (Rhodanese), a cyanide and H2S detoxification enzyme.
AB  - Rhodanese or thiosulfate sulfurtransferase (TST) is a mitochondrial matrix enzyme
      that plays roles in cyanide detoxification, the formation of iron-sulfur proteins
      and the modification of sulfur-containing enzymes. Transsulfuration reaction
      catalyzed by TST is also involved in H(2)S detoxification. To date, no
      polymorphism of the human TST gene had been reported. We developed a screening
      strategy based on a PCR-SSCP method to search for mutations in the 3 exons of TST
      and their proximal flanking regions. This strategy has been applied to DNA
      samples from 50 unrelated French individuals of Caucasian origin. Eleven
      polymorphisms consisting in seven nucleotide substitutions in non-coding regions,
      two silent mutations and two missense mutations were characterized. The
      functional consequences of the identified mutations were assessed in vivo by
      measurement of erythrocyte TST activity and/or in vitro using heterologous
      expression in Saccharomyces cerevisiae or transient transfection assay in HT29
      and Caco-2 cell lines. The P(285)A variant appears to encode a protein with a 50%
      decrease of in vitro intrinsic clearance compared to the wild-type enzyme.
      Additionally, the six polymorphisms located upstream the ATG initiation codon are
      responsible for a significant decrease (ranging from 40% to 73%) in promoter
      activity of a reporter gene compared to the corresponding wild-type sequence.
      This work constitutes the first report of the existence of a functional genetic
      polymorphism affecting TST activity and should be of great help to investigate
      certain disorders for which impairment of CN(-) or H(2)S detoxification have been
      suggested to be involved.

PMID- 16790312
TI  - Adverse effects of T-2 toxin on chicken lymphocytes blastogenesis and its
      protection with Vitamin E.
AB  - T-2 toxin, a trichothecene mycotoxin that is produced by fusarium species, is
      prevalent mainly in cereal crops and poultry feed. One of the major effects of
      this toxin is immunomodulation. The effect of T-2 toxin on chicken lymphocyte
      proliferation in the presence of mitogens and the subsequent protection with
      Vitamin E in both fat and water soluble forms was studied using an MTT
      colorimetric assay. T-2 toxin was administered in concentrations ranging from 0
      to 10ng/mL of lymphocytes in the presence of either concanavalin A (ConA) or
      phytohemagglutinine (PHA-M) at optimum concentration of 333ng/mL and a dilution
      of 1:160 for ConA and PHA-M, respectively. Lymphocyte proliferation in response
      to ConA and PHA-M mitogens was depressed at T-2 doses of 1ng/mL or higher
      (p<0.05). The proliferation was completely abolished at 10ng/mL when the toxin
      was added at 0 time, while it was decreased by 80% when the toxin was added to
      the lymphocytes after 24h. The addition of Vitamin E in the fat soluble form
      (alpha-tocopheryl acetate) did not exert any protection effect against the toxin
      when it was added at either 25 or 100microg. However, when the water soluble form
      (Trolox) was added at a concentration of (200microg) (equivalent to 100microM of
      alpha-tocopherol), it provided considerable protection (p<0.05) against T-2 toxin
      inhibition of lymphocyte proliferation. The difference in the effect between the
      two forms of Vitamin E might be related to their relative solubility in the
      culture media which in turn may affect their availability for protection.

PMID- 16790313
TI  - Expression of crustacean (Callinectes sapidus) molt-inhibiting hormone in
      Escherichia coli: characterization of the recombinant peptide and assessment of
      its effects on cellular signaling pathways in Y-organs.
AB  - A neuropeptide, molt-inhibiting hormone (MIH), negatively regulates the synthesis
      of ecdysteroid molting hormones by crustacean Y-organs. We report here the
      expression of blue crab (Callinectes sapidus) MIH in Escherichia coli. Bacteria
      were transformed with an expression plasmid containing a cDNA insert encoding
      MIH. After induction of protein synthesis, recombinant MIH (recMIH) was detected
      in the insoluble fraction of cell lysates. The insoluble recMIH was refolded and
      purified by reversed-phase high performance liquid chromatography (RP-HPLC). The
      refolded peptide was MIH-immunoreactive and comigrated with native MIH on RP
      HPLC. Mass and CD spectral analyses showed the mass number and secondary
      structure of the recombinant peptide were as predicted for MIH. Bioassays showed
      recMIH dose-dependently suppresses ecdysteroid synthesis by Y-organs. The
      combined results suggest that recMIH is properly folded. In subsequent
      experiments, recMIH was used to assess cellular signaling pathways linked to MIH
      mediated suppression of ecdysteroidogenesis. Incubation of Y-organs with recMIH
      produced an increase in intracellular cGMP content, but had no effect on
      intracellular cAMP. Further, a cGMP analog significantly suppressed ecdysteroid
      production, but neither cAMP analogs nor an activator of adenylyl cyclase had a
      detectable effect on ecdysteroidogenesis. The results are consistent with the
      hypothesis that MIH-induced suppression of ecdysteroidogenesis in Y-organs of C.
      sapidus is mediated by a cGMP second messenger. We anticipate recMIH will be a
      useful tool for additional studies of the cellular actions and physiological
      functions of MIH.

PMID- 16790314
TI  - Triggering of BDNF facilitatory action on neuromuscular transmission by adenosine
      A2A receptors.
AB  - Motor nerve terminals possess adenosine A(2A) receptors and brain derived
      neurotrophic factor (BDNF) TrkB receptors. In the present work we evaluated how
      BDNF actions on neuromuscular transmission would be influenced by adenosine A(2A)
      receptors activation. BDNF (20-100 ng/ml) on its own was devoid of effect on
      evoked endplate potentials (EPPs) recorded intracellularly from rat innervated
      diaphragms paralysed with tubocurarine. However, when BDNF was applied 45 min
      after a brief (2 min) depolarizing KCl (10 mM) pulse or when the adenosine A(2A)
      receptors were activated with CGS 21680 (10 nM), BDNF (20 ng/ml) increased EPPs
      amplitude without influencing the resting membrane potential of the muscle fibre.
      The action of BDNF was prevented by the adenosine A(2A) receptor antagonist, ZM
      241385 (50 nM) as well as by the TrkB receptor phosphorylation inhibitor, K252a
      (200 nM). The PKA inhibitor, H-89 (1 microM), prevented the excitatory effect of
      CGS 21680 (10 nM) on EPPs as well as prevented its ability to trigger a BDNF
      effect. The PLCgamma inhibitor, U73122 (5 microM), did not prevent the excitatory
      action of CGS 21680 (10 nM) on neuromuscular transmission, but abolished the
      action of BDNF in the presence of the A(2A) receptor agonist. The results suggest
      the following sequence of events in what concerns cooperativity between A(2A)
      receptors and TrkB receptors at the neuromuscular junction: A(2A) receptor
      activates the PKA pathway, which promotes the action of BDNF through TrkB
      receptors coupled to PLCgamma, leading to enhancement of neuromuscular
      transmission.

PMID- 16790315
TI  - Enriched environment experience overcomes the memory deficits and depressive-like
      behavior induced by early life stress.
AB  - Stress in early life is believed to cause cognitive and affective disorders, and
      to disrupt hippocampal synaptic plasticity in adolescence into adult, but it is
      unclear whether exposure to enriched environment (EE) can overcome these effects.
      Here, we reported that housing rats in cages with limited nesting/bedding
      materials on postnatal days 2-21 reduced body weight gain, and this type of early
      life stress impaired spatial learning and memory of the Morris water maze and
      increased depressive-like behavior of the forced swim test in young adult rats
      (postnatal days 53-57). Early life stress also impaired long-term potentiation in
      hippocampal CA1 area of slices of young adult rats. Remarkably, EE experience on
      postnatal days 22-52 had no effect on spatial learning/memory and depressive-like
      behavior, but it significantly facilitated LTP in control rats, and completely
      overcame the effects of early life stress on young adult rats. These findings
      suggest that EE experience may be useful for clinical intervention in preventing
      cognitive and affective disorders during development.

PMID- 16790316
TI  - Suppressive treatment of abamectin against Dictyocaulus viviparus and the
      occurrence of resistance in first-grazing-season calves.
AB  - Dictyocaulus viviparus cause severe lung infections and are endemic in some areas
      of temperate and tropical countries. Treatment is based on strategic nematode
      control programs using potent compounds with no reports of drug failure.
      Macrocyclic lactones (MLs) are available at different concentrations and
      combinations and have being used heavily by producers. The objective of this work
      was to determine the efficacy of the MLs ivermectin, moxidectin, doramectin, and
      abamectin, and the combination ivermectin plus abamectin in naturally infected
      calves (n=70). Initial infection was determined by necropsy of tracer animals.
      Faecal larval counts determined that none of the compounds used was able to
      eliminate D. viviparus for up to 28 days after treatment. The "Area Nova" strain
      was isolated for future work.

PMID- 16790317
TI  - Mechanism of central nervous system toxicity by irinotecan.

PMID- 16790318
TI  - Coincidence of increased pulmonary artery pressure and patent septum foramen
      ovale in patients with solid tumors may have a propensity to develop central
      nervous system metastases.

PMID- 16790319
TI  - Losing weight by defecating at night.

PMID- 16790320
TI  - Salt addiction: a different kind of drug addiction.
AB  - Under the headline "drug addiction" the medical world has exclusively been
      interested in psychoactive drugs. For diagnosis of substance dependence
      (addiction), DSM-IV-TR has determined seven criteria, and fulfilling at least
      tree of them signifies addiction. When studied salt intake according to these
      criteria it is seen that most of them are fulfilled, showing that sodium
      chloride, which is not classified under the psychoactive drugs, is capable of
      producing addiction. Namely: at the beginning of salt abstinence, anorexia and
      slight nausea during meal time (withdrawal symptoms); about 1000-fold difference
      of per capita salt consumption between several human societies, and life-long
      continuation of discretional salt intake behaviour (high dose and very long
      duration of use); difficulty of restriction of salt intake (unsuccessful efforts
      to cut down or control); lack of success of salt restriction campaigns in
      hypertensive patients (substance use despite health problem). Additionally, the
      decrease of salt preferences of individuals whose salt intake are restricted for
      some time, and vice versa, signifies tolerance. On the other hand, it is evident
      that as the main culprit of developing systemic hypertension and as producing or
      promoting some other important health problems, salt intake causes millions of
      deaths in the world yearly. The recognition of addicting property of salt will
      facilitate combating these health problems.

PMID- 16790321
TI  - Gene mutation and aneuploidy might cooperate to carcinogenesis by dysregulation
      of asymmetric division of adult stem cells.

PMID- 16790322
TI  - Selective estrogen receptor modulators: A possible new treatment of osteoporosis
      in males.
AB  - More recently, osteoporosis in men has been recognized as an important public
      health problem. Bone loss begins in mid life and is associated with the decline
      of the sex steroids production. Although there is no equivalent of the menopause,
      gonadal function in men is affected in a slow progressive way leading to
      hypogonadism. Testosterone, the major androgen in men, exerts its effect on bone
      by local conversion to 5alpha-dihydrotestosterone or by aromatization to
      estrogens. Several studies have found that estrogen, rather than testosterone,
      levels are more closely correlated with BMD in elderly men. Selective estrogen
      receptor modulator (SERM) raloxifene binds to estrogen receptors and exhibit
      estrogenic effect in bone, but, contrary to estrogen, without feminizing effect.
      There are limited numbers of studies investigating the effects of SERMs in males.
      Animal studies demonstrated that SERMs inhibit bone turnover and prevent bone
      loss in orchidectomised adult male rats. Raloxifene has been shown to increase
      bone mineral density of the hip in men receiving androgen deprivation therapy for
      prostate cancer. Moreover, experimental data demonstrated dramatic increase in
      cell death in human prostate cancer cell lines after the treatment with
      raloxifene. All these observations suggest that SERMs may be useful for the
      prevention and treatment of osteoporosis not only in postmenopausal women but
      also in elderly men. However, our hypothesis should be tested in a proper
      designed clinical trial. Several important issues have to be addressed. Does the
      same drug dose that has been shown to be effective in postmenopausal women should
      be used in men, too? Does treatment with SERMs reduce the fracture risk in men
      and is it comparable to that observed in women? Does treatment with SERMs have
      any beneficial effect on cardiovascular system and prostate cancer? And finally,
      do men experience adverse events other than women treated with SERMs? Answering
      to these questions will have great impact in getting the decision of possible
      SERMs usage in the treatment of osteoporosis in elderly males.

PMID- 16790323
TI  - The evolutionary role of erectile dysfunction.
AB  - Biologic processes that affect the ability of an organism to reproduce are
      subject to heavy evolutionary pressure. Erectile dysfunction (ED), a common
      condition in elderly males, definitely affects the ability of the organism to
      reproduce, and therefore, it is expected to play a significant evolutionary role.
      Whereas oogenesis is limited to young females, spermatogenesis is a lifelong
      process. As a male gets older, the number of (pre-meiotic) mitotic cell divisions
      during spermatogenesis increases, as does the risk of de novo gene mutations. In
      this paper, I examine the hypothesis that ED, in addition to decrease in
      fertility, are two evolutionary safety mechanisms that reduce the probability of
      an ovum being fertilized with genetically altered sperm from an aged or sick
      male. This hypothesis is supported by the parallel rise in the occurrence of ED,
      infertility, and risk of congenital anomalies with age; by the occurrence of
      these three processes in the same medical conditions; and by the presence of a
      theory unifying the etiologies of three processes-the "free radical theory of
      aging". This hypothesis can predict the occurrence of congenital anomalies under
      conditions associated with ED and infertility but are presently not known to be
      associated with congenital anomalies.

PMID- 16790324
TI  - Magnesium supplementation in the treatment of dementia patients.
AB  - Alzheimer's disease is the most common form of dementia. Many risk factors have
      been defined in the literature, and the roles of environmental factors,
      nutrition, some vitamins and trace elements have been investigated. The role of
      magnesium (Mg) in dementia and other degenerative disorders has been the focus of
      increased attention in recent years. Concentration of Mg affects many biochemical
      mechanisms, which consist of N-methyl d-aspartate (NMDA) receptor response to
      excitatory amino acids, stability and viscosity of the cell membrane and toxic
      effects of calcium. Mg usage with drugs like memantine, which has an influence
      via Mg, can be useful in dementia treatment. According to the results of these
      studies, Mg support can facilitate learning and result in improvement in other
      symptoms. Memantine use has shown some benefit in moderate-to-severe Alzheimer's
      disease or for vascular dementia. Mg in the treatment of dementia facilitates
      learning and contributes to improvement in other symptoms; used in conjunction
      with memantine it may serve to increase memantine's symptomatic and
      neuroprotective effects, via its influence on NMDARs.

PMID- 16790325
TI  - Experimental manipulation of male behaviour during copulation in Stenomacra
      marginella (Heteroptera: Largidae): effect on copula duration, female remating
      and oviposition.
AB  - Apparently stimulatory male copulatory behaviour (MCB) is widespread among
      arthropods and it could help males to increase their fitness by inducing
      favourable behavioural and physiological changes in females. The empirical study
      of female responses to MCB is hindered because its experimental manipulation is
      difficult. We have developed a technique for reducing, with minimal disturbance,
      the frequency of MCB in the true bug Stenomacra marginella. Here, we test the
      idea that, in a polygamous species like S. marginella, sexual selection favours
      males whose MCB induces females to increase copula duration (thereby increasing
      the amount of sperm and accessory substances transferred), reduce their sexual
      receptivity to additional males and increase their rate of oviposition. Males
      prevented from performing MCB increased their rate of attempts to perform MCB.
      Copulations with previously mated females were of longer duration than those with
      virgin females, probably as a male adaptation for sperm competition, and MCB
      could have played a role in inducing this effect. Partial or total experimental
      reduction of MCB frequency had no effect on remating rates, because most females
      accepted remating at the first opportunity (1 day after their first copula). The
      probability of egg laying was reduced in females whose first mate was partially
      prevented from performing copulatory courtship, but not in females whose first
      mate was completely prevented from performing copulatory courtship. This is an
      intriguing result and further experiments are needed to understand its causes. We
      hypothesize that MCB evolved as a result of sexual selection.

PMID- 16790326
TI  - Colon-specific drug delivery: Influence of solution reticulation properties upon
      pectin beads performance.
AB  - In this study, pectinate gel beads were produced by ionotropic gelation method
      with different solutions of cross-linking agents and ketoprofen was entrapped as
      model drug. The influence of these formulation parameters was investigated upon
      bead properties and upon their performance to target the colon. Zinc pectinate
      beads obtained with 10% of counter-ions solution at pH 1.6 exhibited the
      strongest gel network due to "egg-box" dimmer formation helped by hydrogen
      bonding. Furthermore the gel network formed at low pH was arranged in a compact
      three-fold conformation. Thus, this matrix structure in enteric capsules induced
      the lowest drug release in the upper gastro-intestinal tract (pH 1.2 following by
      pH 7.4). However ketoprofen release occurred specifically in the colon thanks to
      the presence of pectinolytic enzymes and the release rate can be modulated by the
      counter-ion concentration during the reticulation process. Therefore this
      approach using pectinate beads is very promising as efficient carrier for
      specific delivery of drug into the colon, after oral administration.

PMID- 16790327
TI  - The focused ion beam technique: a useful tool for pharmaceutical
      characterization.
AB  - Focused ion beam (FIB) instrumentation, a hybrid of the scanning electron
      micrsocope, ion milling and computer-aided design systems, has special uses in
      the electronic and semiconductor industries as a tool for failure analysis and
      device development. This paper examines the pharmaceutical applications of the
      FIB, particularly microscopic analysis of microspheres. With the FIB, microsphere
      structures were peeled off, layer by layer, and the structure of each layer was
      simultaneously observed under scanning microscopy. The particles had a wrinkled
      but non-porous surface. Going deeper, some holes appeared, with size and numbers
      increasing toward the particle center. This unique method precisely investigated
      the inner structure of particles, layer by layer. Then, by FIB milling, samples
      were extracted with an accuracy of localization of 50nm from specific parts of
      the microspheres and prepared to a 200nm uniform thickness film for examination
      under transmission electron microscopy. The FIB method also has the potential for
      a wide range of other quantitative and qualitative analysis of dosage forms and
      materials.

PMID- 16790328
TI  - Enhanced anti-tumor activity and alleviated hepatotoxicity of clotrimazole-loaded
      suppository using poloxamer-propylene glycol gel.
AB  - To develop a novel clotrimazole-loaded poloxamer-based suppository with enhanced
      anti-tumor activity and alleviated hepatotoxicity, the melting point of various
      formulations composed of P 188 and propylene glycol were investigated. The
      dissolution and anti-tumor activity of clotrimazole delivered by the poloxamer
      based suppository was performed. Furthermore, the hepatotoxicity of clotrimazole
      was carried out after its rectal administration compared to oral administration
      in mice. The poloxamer mixtures composed of P 188 and propylene glycol were
      homogeneous phases. P 188 greatly affected the melting point of poloxamer
      mixtures. In particular, the poloxamer mixture [P 188/propylene glycol (70%/30%)]
      with the melting point of about 32 degrees C was a solid form at room temperature
      and instantly melted at physiological temperature. The ratio of P 188/propylene
      glycol greatly affected the dissolution rates of clotrimazole from poloxamer
      based suppository. Dissolution mechanism analysis showed the dissolution rate of
      clotrimazole from poloxamer-based suppositories was independent of the time. The
      clotrimazole-loaded suppository with P 188 and propylene glycol could not
      irritate or damage the rectal tissues of rats and gave the improved anti-tumor
      activity in a dose-dependent manner at mouse. Furthermore, its rectal
      administration decreased the hepatotoxicity compared to oral administration.
      Thus, the poloxamer-based solid suppository system with clotrimazole/P
      188/propylene glycol was an effective rectal dosage form for the treatment of
      tumors with alleviated adverse effects.

PMID- 16790329
TI  - Inhibition of liver metastasis by all-trans retinoic acid incorporated into O/W
      emulsions in mice.
AB  - All-trans retinoic acid (ATRA) was incorporated into lipid emulsions in an
      attempt to alter its distribution characteristics and improve its inhibition of
      liver cancer metastasis. Lipid emulsions composed of egg phosphatidylcholine,
      cholesterol, and soybean oil were the optimized carriers for ATRA delivery, as
      shown by the submicron particle size and high incorporation efficiency. The
      particle size and zeta potential of ATRA incorporated into emulsions were about
      133 nm and -11 mV, respectively. In vitro drug release study demonstrated that
      the release of ATRA from emulsions was sustained in the absence and present of
      bovine serum albumin, suggesting that ATRA was stable when incorporated in
      emulsions. After intravenous administration in mice, [3H]cholesteryl hexadecyl
      ether incorporated into emulsion, which is the inherent distribution of
      emulsions, accumulated gradually mainly in the liver. The blood concentration and
      hepatic accumulation of [3H]ATRA incorporated into emulsion was significantly
      higher than that of serum dissolving [3H]ATRA, which represent the original
      distribution characteristic of free ATRA. In a murine liver metastasis model by
      colon adenocarcinoma, the liver metastasis number and liver weight were
      significantly reduced and the survival time of mice was prolonged following
      intravenous injection of ATRA incorporated into emulsions.

PMID- 16790330
TI  - Evaluation of some plants used in Turkish folk medicine against parasitic
      infections for their in vivo anthelmintic activity.
AB  - Ethanolic and aqueous extracts obtained from nine plant species from seven
      families selected depending on their use in Turkish folk medicine, including
      Citrillus lanatus (Thunb.) Matsum. (seed), Jasminum fruticans L. (branches),
      Juniperus drupacea Labill. (fruits), Juniperus nana L. (fruit and leaves),
      Juniperus oxcycedrus L (fruit and leaves), Mentha longifolia L. (herba), Pinus
      nigra ssp. pallasiana (Lamb.) Richt. (fruits), Plantago lanceolata L. (leaves),
      and Zea mays L. (seed) were evaluated for their in vivo anthelmintic activity.
      Among the plant extracts studied, both ethanolic and aqueous extracts of Jasminum
      fruticans, Mentha longifolia and Pinus nigra ssp. pallasiana, the aqueous
      extracts of Zea mays, the ethanolic extracts of Citrillus lanatus, Juniperus
      drupacea (fruit), Juniperus oxcycedrus and Plantago lanceolata displayed
      significant anthelmintic activity against pinworms, Syphacia obvelata and
      Aspiculuris tetraptera, in mice. Rest of the extracts from plants did not show
      any remarkable anthelmintic activity. The results were considered significant at
      p<0.05.

PMID- 16790332
TI  - Association between D18S474 locus on chromosome 18q12 and idiopathic generalized
      epilepsy.
AB  - Idiopathic generalized epilepsy is one of the most common forms of epilepsy. The
      aetiology of IGE is genetically determined, but the pattern of inheritance is
      still undefined. Recent studies in common IGE showed evidence for linkage on
      chromosome 18q12 at the D18S474 locus. The aim of our study was to compare the
      distribution of allelic variants of D18S474 locus in children affected by
      generalized tonic-clonic seizures and in healthy controls. We studied 295
      children: 121 cases and 174 controls. We found that the D18S474(8) allele was
      significantly more frequent and D18S474(9) significantly less frequent in cases
      compared with controls (p<.001). In conclusions, our findings show the
      association between the D18S474 marker and IGE in which early onset GTCS
      represent the most prevalent seizure type.

PMID- 16790331
TI  - Kainic acid dose affects delayed cell death mechanism after status epilepticus.
AB  - Kainic acid (KA)-induced status epilepticus (SE) produces hippocampal neuronal
      death, which varies from necrosis to apoptosis or programmed cell death (PCD). We
      examined whether the type of neuronal death was dependent on KA dose. Adult rats
      were induced SE by intraperitoneal injection of KA at 9 mg/kg (K9) or 12 mg/kg
      (K12). Hippocampal neuronal death was assessed by TUNEL staining, electron
      microscopy, and Western blotting of caspase-3 on days 1, 3 and 7 after SE
      induction. K12 rats showed higher a mortality rate and shorter latency to the
      onset of SE when compared with K9 rats. In both groups, acidophilic and pyknotic
      neurons were evident in CA1 at 24h after SE and neuronal loss developed from day
      3. The degenerated neurons became TUNEL-positive on days 3 and 7 in K9 rats but
      not in K12 rats. Caspase-3 activation was detected on days 3 and 7 in K9 rats but
      was undetectable in K12 rats. Ultrastructural study revealed shrunken neurons
      exhibiting pyknotic nuclei containing small and dispersed chromatin clumps 24h
      after SE in CA1. No cells exhibited apoptosis. On days 3 and 7, the degenerated
      neurons were necrotic with high electron density and small chromatin clumps.
      There were no ultrastructural differences between the K9 and K12 groups. These
      results revealed that differences in KA dose affected the delayed cell death (3
      and 7 days after SE); however, no effect was seen on the early cell death (24h
      after SE). Moderate-dose KA induced necrosis, while low-dose KA induced PCD.

PMID- 16790334
TI  - Arsukibacterium ikkense gen. nov., sp. nov, a novel alkaliphilic, enzyme
      producing gamma-Proteobacterium isolated from a cold and alkaline environment in
      Greenland.
AB  - A novel aerobic, Gram-negative, non-pigmented bacterium, GCM72(T), was isolated
      from the alkaline, low-saline ikaite columns in the Ikka Fjord, SW Greenland.
      Strain GCM72(T) is a motile, non-pigmented, amylase- and protease-producing,
      oxidase-positive, and catalase-negative bacterium, showing optimal growth at pH
      9.2-10.0, at 15 degrees C, and at 3% (w/v) NaCl. Major fatty acids were C(12:0) 3
      OH (12.2+/-0.1%), C(16:00) (18.0+/-0.1%), C(18:1)omega7c (10.7+/-0.5%), and
      summed feature 3 comprising C(16:1)omega7c and/or iso-C(15:0) 2-OH (36.3+/-0.7%).
      Phylogenetic analysis based on 16S rRNA gene sequences showed that isolate
      GCM72(T) was most closely related to Rheinheimera baltica and Alishewanella
      fetalis of the gamma-Proteobacteria with a 93% sequence similarity to both. The
      G+C content of DNA isolated from GCM72(T) was 49.9mol% and DNA-DNA hybridization
      between GCM72T and R. baltica was 9.5%. Fatty acid analysis and G+C content
      supports a relationship primarily to R. baltica, but several different features,
      such as a negative catalase-response and optimal growth at low temperature and
      high pH, together with the large phylogenetic distance and low DNA similarity to
      its closest relatives, lead us to propose a new genus, Arsukibacterium, gen.
      nov., with the new species Arsukibacterium ikkense sp. nov. (type strain is
      GCM72(T)).

PMID- 16790333
TI  - Do longevity mutants always show trade-offs?
AB  - A number of genetic mutations that substantially increase longevity have been
      discovered in model organisms. Although these long-lived mutants have provided
      many insights into the factors that affect longevity, the results from such
      studies should be interpreted with caution. In particular, at least some of these
      mutations may be poor guides to human medical intervention because they often
      have deleterious side effects on important biological functions.

PMID- 16790335
TI  - Down-regulation of TGF-beta1-induced type I collagen synthesis by AP-1
      transcription factor decoy in scleroderma fibroblasts.

PMID- 16790337
TI  - Capillary blood gases in acute exacerbations of COPD by Ross Murphy et al.

PMID- 16790336
TI  - Production of an antimicrobial substance against Cryptococcus neoformans by
      Paenibacillus brasilensis Sa3 isolated from the rhizosphere of Kalanchoe
      brasiliensis.
AB  - An antifungal substance produced by Paenibacillus brasilensis strain Sa3 was
      preliminary characterized and showed to be stable after treatment with different
      enzymes and organic solvents and at a wide range of pH, and presented a molecular
      weight between 3 and 10 kDa. In vitro antagonism of this strain towards
      Cryptococcus neoformans was investigated by optical and electronic microscopic
      analyses and a fungicidal effect on C. neoformans was observed. Ultrastructural
      analysis showed intense changes on the fungus when it was paired cultured with
      strain Sa3, mainly the detachment of the capsule from the cell wall and the
      presence of altered organelles in the cytoplasm. This novel antifungal substance
      produced by P. brasilensis Sa3 may represent a new insight in antifungal therapy
      mainly against emergent fungi. Also, prospective studies on rhizobacteria of
      plants as Kalanchoe brasiliensis may offer a potential source for the discovery
      of bioactive compounds with medical value.

PMID- 16790338
TI  - Ignition and burning rates of segregated waste combustion in packed beds.
AB  - Recent developments in national recycling and re-use programmes for municipal
      waste have led to segregation of an increasing proportion of waste to enhance
      material recovery. Several of the segregated streams contain materials that can
      not viably be re-used or recycled but can be used for energy recovery. In this
      study, the combustion of cardboard and waste wood was investigated in a small
      scale packed bed reactor in order to provide fundamental data for the
      design/operation of moving bed furnaces. Key parameters of combustion including
      the ignition and burning rates were evaluated for various air flowrates and
      compared to the modelling results. Two successive stages of combustion were
      identified for both samples: the propagation of ignition front into the bed and
      combustion of the fuel above the ignition front. The burning rate of cardboard
      reached a peak of about 300 kg/m(2)h at the air flowrate of 936 kg/m(2)h and
      decreased at higher air flowrates. For waste wood, both the ignition and burning
      rates increased in the tested range of the air flowrate up to 702 kg/m(2)h, of
      which the values were very close to those for the cardboard. The model prediction
      was in good agreement with the test results for waste wood. However, the burning
      rate for cardboard was under-predicted due to strongly irregular shapes of the
      fuel.

PMID- 16790339
TI  - Information provision for patients by breast cancer teams about the side-effects
      of hormone treatments.
AB  - The choice of adjuvant hormone treatments in post-menopausal women with breast
      cancer increasingly includes anastrozole as an alternative to tamoxifen. Clearly
      there may be overlapping side-effects, but other important differences may have
      serious implications for health and quality of life. Patients consequently
      require information regarding the side-effects of recommended treatments and
      their comparisons. This study evaluates the extent of information provision about
      the side-effects of adjuvant anastrozole and tamoxifen by respective breast
      cancer professionals within 16 different breast care teams in the United Kingdom
      (UK). The study used interviews with individual members of breast cancer
      multidisciplinary teams (surgeons, oncologists and breast care nurses) from 11
      cancer centres and 3 district general hospitals, to examine the information they
      give to patients relating to the side-effects of tamoxifen and anastrozole. The
      results show that vasomotor symptoms were the most frequently mentioned side
      effect for both treatments. All teams, in large part addressed the adverse
      effects of both treatments (endometrial cancer and thrombo-embolic events for
      tamoxifen and anastrozole-associated loss of bone density). There was variation
      between the different professionals as to how frequently side-effects were
      mentioned. The greatest discrepancies occurred between the information given by
      team members and that included in patient information leaflets. In some cases,
      important information pertaining to side-effects was omitted from leaflets. This
      study suggests the need to standardise information-provision nationally in the UK
      and within breast cancer teams regarding the evidence-based side-effects of
      tamoxifen and anastrozole.

PMID- 16790340
TI  - Role of complementary and alternative medicine in the care of patients with
      breast cancer: report of the European Society of Mastology (EUSOMA) Workshop,
      Florence, Italy, December 2004.
AB  - The aim of the European Society of Mastology (EUSOMA) Workshop, Florence, Italy,
      December 2004, was to produce guidelines on the use of complementary and
      alternative medicine (CAM) for breast cancer. The widespread use of CAM has to be
      acknowledged and the reasons for this understood. Deficiencies in the practice of
      conventional medicine that lead to the adoption of CAM need to be addressed. At
      the same time, CAM use for breast cancer should be quality controlled, avoiding
      double standards in evaluation, whilst recognising the problems of CAM research.
      These guidelines, which appear in an accompanying paper, aim to help oncologists
      and cancer patients alike.

PMID- 16790341
TI  - Low temperature conversion of rice husks, eucalyptus sawdust and peach stones for
      the production of carbon-like adsorbent.
AB  - In this study, the feasibility of preparing effective adsorbents from unmitigated
      agroforestry wastes was investigated. Three different kinds of carbon-like
      materials were produced by low temperature pyrolysis (LTC, <500 degrees C) of the
      raw materials rice husks, eucalyptus sawdust and peach stones. The carbon-like
      materials were characterized by instrumental methods (SEM,X-RDS,BET,MAS
      RMN,FTIR), physico-chemical adsorption (iodine-, methylene blue- and phenazone
      number; acetic acid adsorption isotherm; textile dyes- and carbohydrate
      adsorption), and heat value determination. The produced materials, which showed
      appreciable adsorption capacity, can be considered as precursors for the
      production of active coal or even be used directly as well.

PMID- 16790342
TI  - Stand density and basal area prediction of unthinned irrigated plantations of
      Eucalyptus camaldulensis in the hot desert of India.
AB  - Growth modelling is an essential prerequisite for evaluating the consequences of
      a particular management action on the future development of a forest ecosystem.
      Mathematical growth models are not available for many tree species in India. The
      objectives of this study were to estimate potential stand density and model the
      actual tree density and basal area development in pure even-aged stands of
      Eucalyptus camaldulensis. Relationships between quadratic mean diameter and stems
      ha(-1) were developed, and parameter values of this relationship were used to
      establish the limiting density line. Two different models were compared to
      describe the natural decrease of stem number. The model including site index as
      one of the variables performed slightly better than the model without site index.
      Seven different stand level models also were compared for predicting basal area
      in the stands. The models tested in this paper belong to the path invariant
      algebraic difference form of a nonlinear model. They can be used to predict
      future basal area as a function of stand variables like initial basal area, age
      or dominant height, and stems ha(-1) and are crucial for evaluating different
      silvicultural treatment options. The performance of the models for basal area was
      evaluated using different quantitative criteria. Among the seven models tested,
      the two models proposed by Pienaar and Shiver and Forss et al. had the best
      performance. The equations proposed to predict future basal area and stem number
      are related and, therefore, simultaneous regression technique has also been used
      to investigate the differences between parameter coefficients obtained by fitting
      the equations separately and jointly.

PMID- 16790343
TI  - Production of lactic acid with loofa sponge immobilized Rhizopus oryzae RBU2-10.
AB  - Lactic acid production by Rhizopus oryzae RBU2-10 immobilized in loofa sponge was
      evaluated. Shape and texture of loofa sponge, which was obtained from the mature
      dried fruit of Luffa cylindrica, remained intact after its treatment with buffers
      of varying pH and following its repeated autoclaving for up to four cycles (121
      degrees C, 20 min per cycle). The medium having four pieces of loofa sponge
      (1.008 cm(3)) per 100 ml medium and inoculated with 3 x1 0(6) spores ml(-1)
      resulted maximum production (80.75 g l(-1)) of lactic acid in 48 h of
      fermentation. Repeated batch fermentation for lactic acid production could be
      carried out for 10 cycles. Remarkably higher levels of productivity (1.66-1.84 g
      l(-1)h(-1)) was obtained during first five cycles of fermentation with a maximum
      productivity (1.84 g l(-1)h(-1)) obtained during third cycle of fermentation.

PMID- 16790344
TI  - Performance of a commercial inoculum for the aerobic biodegradation of a high fat
      content dairy wastewater.
AB  - The effectiveness of a commercial inoculum for degrading a dairy wastewater with
      high fat content was evaluated, and compared with an activated sludge inoculum
      from a dairy wastewater treatment pond. Both inocula reached similar chemical
      oxygen demand removal in batch experiments. The population dynamics was also
      studied by determining heterotrophic counts. Predominant microorganisms were
      differentiated by colony morphology and genomic fingerprinting (BOX-PCR)
      analysis. The higher population diversity and the wider range of CO2 production
      rate observed in batch reactors inoculated with activated-sludge, indicated that
      microorganisms from this inoculum were well adapted and may have had synergic
      activity for the degradation of the dairy effluent. When the bioreactor was
      operated with the commercial inoculum in continuous mode, according to its
      microbial growth kinetics, other microorganisms became predominant. These results
      showed that inoculated microorganisms did not persist in the open system and
      periodic addition of microorganisms may be needed to achieve a high performance
      treatment.

PMID- 16790345
TI  - Batch production of polyhydroxyalkanoate by low-polyphosphate-content activated
      sludge at varying pH.
AB  - Polyhydroxyalkanoate (PHA), a biodegradable plastic, can be produced from excess
      activated sludge by utilizing intracellular glycogen and polyphosphate as energy
      sources under growth-limiting conditions. Activated sludge of 2%, 6%, and 8%
      polyphosphate with similar glycogen content of 33% was investigated for batch PHA
      production by varying the pH values from 6 to 8. Acetate applied at 1000 mg COD/L
      was almost exhausted within 80 min of anaerobic stage. The remaining glycogen in
      the sludge was higher at a lower pH because of less energy used for acetate
      uptake. Highest PHA content of 51% was obtained from sludge with an 8%
      polyphosphate content at pH 8. PHA production occurred rapidly within the first
      20 min, with a productivity rate of 2.19 g PHA/L-h. The results in this study
      indicate that PHA production by using activated sludge is a promising alternative
      to a typical pure culture approach.

PMID- 16790346
TI  - Uptake of cationic dyes from aqueous solution by biosorption onto granular
      kohlrabi peel.
AB  - A new, low cost, locally available biomaterial was tested for its ability to
      remove cationic dyes from aqueous solution. Granules prepared from kohlrabi peel
      had been utilized as a sorbent for uptake of three cationic dyes, methylene blue
      (MB), neutral red (NR) and acridine orange (AO). The effects of various
      experimental parameters (e.g., dye concentration, particle size, initial pH,
      contact time and other factors) were investigated and optimal experimental
      conditions were ascertained. Above the value of initial pH 4, three dyes studied
      could be removed effectively. The isothermal data fitted the Langmuir model in
      the case of NR sorption and the Freundlich model for all three dyes sorption. The
      biosorption processes followed the pseudo-first-order rate kinetics. The results
      in this study indicated that kohlrabi peel was an attractive candidate for
      removing cationic dyes from the dye wastewater.

PMID- 16790349
TI  - Early investigation and treatment of obstructive sleep apnoea after acute stroke.
AB  - Obstructive sleep apnoea (OSA) is an independent risk factor for hypertension,
      which is a major cause of stroke. The prevalence and associations of OSA in a
      cohort of stroke patients were studied. The safety and tolerability of early
      treatment with nasal continuous airways pressure (nCPAP) was also assessed.
      Consecutive subjects admitted with acute stroke were assessed clinically,
      radiologically and with scales assessing prior OSA risk, dysphagia and
      disability. Sleep studies were performed within the first few days of admission
      using a portable diagnostic system. Twenty-nine of 55 (53%) subjects had evidence
      of OSA, using an apnoea-hypopnoea index (AHI) of 10 or greater. The AHI was
      significantly associated with an index of prior OSA symptoms, but not with
      history of hypertension, degree of dysphagia, or type and severity of stroke. Use
      of a portable diagnostic system for detecting OSA in the acute stroke setting was
      well tolerated. OSA is common after acute stroke and exceeds rates seen in
      control populations of similar age (53% vs. 11%). Early treatment with nCPAP was
      effective and well tolerated.

PMID- 16790350
TI  - Entacapone improves complex movement performance in patients with Parkinson's
      disease.
AB  - BACKGROUND: A possible strategy to prolong plasma metabolism of
      Levodopa/Carbidopa (LD/CD) is Entacapone addition (EN), which improves impaired
      motor behaviour in patients with Parkinson's disease (PD). AIMS OF THE STUDY:
      Objectives were to evaluate the clinical response to an increased dopaminergic
      substitution with EN by clinical rating and assessment of complex motions and to
      investigate the change of movement in PD patients during repeat drug
      administration during an eight hour interval. METHODS: We used peg insertion with
      a computer based device and clinical rating for assessment of motor function in
      20 treated PD patients. They received LD/CD and then the same LD/CD dosage plus
      EN in a standardised, open label fashion. RESULTS: Motor scores and performance
      of the instrumental task were significantly better and the fluctuation of
      movement was less intense during the LD/CD/EN condition according to the motor
      test outcomes. CONCLUSION: EN supplementation improves motor symptoms and
      provides a more continuous movement behaviour in PD patients.

PMID- 16790351
TI  - Spike-wave stupor in a patient with metabolic encephalopathy.

PMID- 16790352
TI  - Short-term effects of methylprednisolone on cerebral volume in multiple sclerosis
      relapses.
AB  - We prospectively investigated the short-term effects of intravenous methyl
      prednisolone (IVMP) on cerebral volume in patients suffering a multiple sclerosis
      (MS) relapse. Ten patients underwent MRI brain studies immediately before and
      after IVMP treatment, and 4 and 8 weeks later. Whole brain volumes decreased
      significantly over the 8-week period. The greatest change occurred during IVMP
      administration. This has implications for MS treatment trials using cerebral
      atrophy as an endpoint.

PMID- 16790353
TI  - Relative positions of the contacts on the cartilage surfaces of the knee joint.
AB  - The goal of this project was to determine the centers of contacts (points of
      closest approach of the articular surfaces) for the tibio-femoral and patello
      femoral joints throughout the flexion range, with a focus on high flexion where
      there is potential overlap between the contacts. The purpose was to determine the
      implications to the design of joint replacements and tissue engineered implants.
      Eight cadaveric knees were mounted in a rig with different loading combinations
      applied to the femur, including axial load, anterior/posterior shear, and
      internal/external torque. The range of flexion was 0 degrees to 155 degrees .
      Reference points on the bones measured during the experiments were used to later
      reconstruct an accurate 3D computer model of the multiple joint positions and
      determine the centers of contact between the opposing bearing surfaces. The tibio
      femoral contact at 0 degrees flexion was displaced 5 mm anterior to the notch
      (the end point of the articular cartilage on the mid-line of the femoral sulcus)
      on the medial side, while remaining level with the notch on the lateral side. The
      patella contacts on the femur extended 15 mm posterior to the intercondylar notch
      with a centerline between the lateral and medial paths being several millimeters
      lateral to the center of the femur. The centers of the patella contacts were
      close to the inner margin of the medial condyle and did not directly overlap with
      the centers of the tibial contacts. On the lateral side the patella contacts
      ended where the tibial contacts began. For applications to medial unicondylar
      knee replacement design it was shown that patellar impingement on the anterior of
      the femoral component would occur at 110 degrees flexion. For TKR design, a
      continuous patella contact up to high flexion could be obtained by extending the
      trochlea 15 mm posterior to the intercondylar notch.

PMID- 16790354
TI  - Effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone
      consolidation on distraction osteogenesis: a preliminary study in rabbit
      mandibles.
AB  - AIM: To examine the effectiveness of administering recombinant human bone
      morphogenetic protein-2 (rhBMP-2) in distraction osteogenesis. MATERIAL AND
      METHODS: Twenty-one mature male Japanese white rabbits underwent unilateral
      mandibular osteotomy. After 5 days, the osteotomized mandibles were distracted
      1mm/day for 10 days. On the first day (groups A-1 [n=4] and A-2 [n=4]) or on the
      last day (group B [n=5]) of distraction, rhBMP-2 mixed with collagen gel was
      injected into the distraction zone. In control groups (groups C-1 [n=4] and C-2
      [n=4]), the mandibles were distracted without rhBMP-2 injection. At the end of
      the distraction period (groups A-1 and C-1) and after 2 weeks of consolidation
      (groups A-2, B, and C-2), the distracted mandibles were harvested and examined
      with soft radiographs, peripheral quantitative computed tomography (pQCT), and
      microscopy. RESULTS: Radioopacity was more marked in the distraction zone of the
      groups with rhBMP-2 than in control groups. The mineral density of the cortical
      bone (BMD) was higher in groups B and A-2 than in group C-2. Histologically, bone
      formation was more advanced in groups A-2 and B than in group C-2. The cortical
      BMD was higher in group A-1 than in group C-1. Histologically, bone formation was
      more advanced in groups A-2 and B than in group C-2. CONCLUSION: These results
      suggest that rhBMP-2 promotes bone formation in distraction osteogenesis.

PMID- 16790355
TI  - beta2-Adrenoceptor blockade partially restores ex vivo TNF production following
      hemorrhagic shock.
AB  - The aim of the study was to assess the mechanisms through which leukocyte
      deactivation occurs upon hemorrhagic shock. In particular, the influence of beta
      adrenergic tone was evaluated. BALB/c mice were hemorrhaged and resuscitated 60
      min after hemorrhage. Animals were sacrificed 60 min later by exsanguination.
      Blood from exsanguination was cultured ex vivo with lipopolysaccharide (LPS) and
      heat-killed Staphylococcus aureus Cowan I (SAC). Hemorrhage resulted in a major
      decrease of LPS-induced TNF production whereas IL-10 production was significantly
      enhanced. Selective beta(2)-adrenoceptor antagonists (ICI 118,551) attenuated the
      decrease in TNF production and further enhanced IL-10 production. Hemorrhage did
      not alter SAC-induced TNF production levels whereas IL-10 production was
      increased. ICI 118,551 further increased the production of both TNF and IL-10.
      These data suggest that leukocyte deactivation after LPS stimulation is not a
      generalized phenomenon since TNF production was maintained when another microbial
      activator was used. IL-10 production was enhanced after hemorrhagic shock,
      independently of the nature of the triggering agent. Finally, this study
      demonstrates that beta(2)-adrenoceptor ligands play an important role in blood
      leukocyte deactivation to LPS after hemorrhagic shock.

PMID- 16790356
TI  - The effects of a dominant connexin32 mutant in myelinating Schwann cells.
AB  - Mutations in GJB1, the gene encoding the gap junction protein connexin32 (Cx32),
      cause X-linked Charcot-Marie-Tooth disease, an inherited demyelinating peripheral
      neuropathy. We generated transgenic mice that express the R142W mutation in
      myelinating Schwann cells. The R142W mutant protein was aberrantly localized to
      the Golgi, indicating that it does not traffic properly, but the molecular
      organization of the myelin sheath, including the localization of Cx29, another
      connexin expressed by myelinating Schwann cells, was not disrupted. In a wild
      type background, this mutation dramatically decreased the level of wild type
      mouse Cx32 in immunoblots of sciatic nerve and caused demyelination. The
      expression of wild type human Cx32 with the same transgenic construct had
      different effects-increased amounts of Cx32, normal localization of Cx32 at nodes
      and incisures, and split myelin sheaths. Thus, the R142W mutant protein has
      dominant effects that are distinct from overexpression.

PMID- 16790357
TI  - Bi-directional control of motor neuron dendrite remodeling by the calcium
      permeability of AMPA receptors.
AB  - Motor neurons express particularly high levels of the AMPA receptor subunit
      GluR1(Q)flip (GluR1(Q)i) during the period in early postnatal life when their
      dendritic tree grows and becomes more branched. To investigate how GluR1
      containing AMPA receptors contribute to dendrite morphogenesis, we characterized
      a mutant form of GluR1 (containing a histidine in the Q/R editing site) with
      unique electrophysiological properties. Most notably, AMPA receptors assembled
      from GluR1(H)i display less calcium permeability than AMPA receptors assembled
      from GluR1(Q)i. Expression of GluR1(Q)i in vivo or in vitro led to an increase in
      dendrite branching with no net change in the overall tree size while GluR1(H)i
      led to a loss of branches and a net reduction in overall tree size. GluR1(H)i
      dependent dendrite atrophy is mediated by protein phosphatase 2B. The results
      suggest that the electrophysiological properties of cell surface AMPA receptors,
      specifically their permeability to calcium, can be a central determinant of
      whether the dendrites undergo activity-dependent branching or atrophy.

PMID- 16790358
TI  - Myoelectric manifestations of fatigue at low contraction levels in subjects with
      and without chronic pain.
AB  - The aim of the present study was to investigate differences in myoelectric
      responses to fatigue development between cases with chronic neck-shoulder pain
      (n=10) and healthy controls (n=10) during a low force level sustained
      contraction. Subjects performed a 15-min isometric shoulder elevation at a force
      level of 40 N (sustained contraction), preceded and followed by a step
      contraction, consisting of five force levels from 20 to 100 N. EMG recordings
      were made with a two-dimensional electrode array on the upper trapezius of the
      dominant side. Root-mean-square (RMS(G)), median power frequency (FMED(G)),
      conduction velocity (CV), number of motor unit action potentials per second (MUAP
      Rate) and MUAP shape properties were estimated. Changes over time and differences
      between the groups were statistically evaluated with a linear mixed model. During
      the sustained contraction, cases showed less increase in RMS(G) than controls
      (controls: 58.5%, cases: 33.0%). FMED(G) and CV decreased in controls (FMED(G): 
      6.3%, CV: -5.3%) and stayed constant (FMED(G)) or slightly increased (CV, 3.15%)
      in cases. Overall, cases showed a less pronounced myoelectric response to the
      fatiguing task than controls, which may be related to additional recruitment of
      higher-threshold MUs. A possible explanation might be that cases were already
      (chronically) fatigued before the experiment started.

PMID- 16790359
TI  - Influence of seamlessness between pre- and poststimulus alpha rhythms on visual
      evoked potential.
AB  - The influence of seamlessness between the prestimulus alpha rhythm and
      poststimulus alpha ringing on the visual evoked potentials (VEPs) was
      investigated. Subjects passively viewed a series of 1000 flash stimuli with their
      eyelids closed, and their VEPs were recorded. The instantaneous phase angle of
      the alpha rhythm in each subject was calculated by using a two-cycle complex
      exponential sequence. VEPs were classified into four subsets according to
      seamlessness: how well the phase angle of the prestimulus alpha rhythm and the
      backward-extrapolated phase angle from poststimulus alpha ringing were
      synchronized. VEPs of each subset were averaged. A one-way repeated measures
      analysis of variance revealed that seamlessness significantly affected the
      amplitude of P100. Moreover, the level of seamlessness significantly affected the
      phase locking index. Two models for the generating evoked potentials have been
      proposed; one is the phase resetting model (Makeig, S., Westerfield, M., Jung,
      T.P., Enghoff, S., Townsend, J., Courchesne, E., Sejnowski, T.J., 2002. Dynamic
      brain sources of visual evoked responses. Science 295, 690-694) and the other is
      the evoked model (Makinen, V., Tiitinen, H., May, P., 2005. Auditory event
      related responses are generated independently of ongoing brain activity.
      Neuroimage 24, 961-968). These results suggest that alpha ringing is possibly
      generated by the phase-resetting alpha rhythm and support the phase resetting
      model.

PMID- 16790360
TI  - Castrating older lambs: what are the issues?

PMID- 16790361
TI  - Pseudoathetosis caused by migrated cervical disc.
AB  - Although pseudoathetosis has been described in various conditions, it has been
      rarely reported in patients with epidural lesions. We report the first case of a
      patient with pseudoathetosis caused by a migrated cervical disc. The patient was
      a 76-year-old woman who presented with progressive clumsiness of the hands and
      athetotic movements. Electrophysiological studies revealed normal peripheral
      nerve conduction and delayed and attenuated cortical SEPs. Spinal MRI revealed an
      epidural mass with gadolinium enhancement at the C3-4 level. An anterior cervical
      surgery disclosed a migrated disc, and its removal resulted in a marked
      improvement. Migrated cervical disc should be considered in patients with a
      profound sensory loss and pseudoathetosis in the hands, because this condition is
      treatable.

PMID- 16790362
TI  - Adhesions that mediate invasion.
AB  - Infiltration of new tissue areas requires that a mammalian cell overcomes the
      physical and biochemical barrier of the surrounding extracellular matrix. Cell
      migration during embryonic development, and growth, invasion and dispersal of
      metastatic tumor cells depend to a large extent on the controlled degradation of
      extracellular matrix components. Localized degradation of the surrounding matrix
      is seen at defined adhesive (podosomes) and/or protrusive (invadopodia) locations
      in a variety of normal cells and aggressive carcinoma cells, suggesting that
      these membrane-associated cellular devices have a central role in mediating
      polarized migration in cells that cross-tissue boundaries. Here, we will discuss
      the recent advances and developments in this field, and provide our provisional
      outlook into the future understanding of the principles of focal extracellular
      matrix degradation by podosomes and invadopodia.

PMID- 16790363
TI  - DNA binding mode of ruthenium complexes and relationship to tumor cell toxicity.
AB  - Transition-metal-based compounds constitute a discrete class of
      chemotherapeutics, widely used in the clinic as antitumor and antiviral agents.
      Examples of established antitumor metallodrugs, routinely used in the clinic, are
      cisplatin [cis-diamminedichloroplatinum(II)] and its analogues carboplatin and
      oxaliplatin. However, drug resistance and side effects have limited their
      clinical utility. These limitations have prompted a search for more effective and
      less toxic metal-based antitumor agents. Some of the efforts have been directed
      in the design of non-platinum, transition-metal-based antitumor agents and
      ruthenium complexes have attracted much interest as alternative drugs to
      cisplatin in cancer chemotherapy. Ruthenium complexes demonstrate similar ligand
      exchange kinetics to those of platinum(II) antitumor drugs already used in the
      clinic while displaying only low toxicity. This is in part due to the ability of
      ruthenium complexes to mimic the binding of iron to molecules of biological
      significance, exploiting the mechanisms that the body has evolved for transport
      of iron. In addition, the redox potential between the different accessible
      oxidation states occupied by ruthenium complexes enables the body to catalyze
      oxidation and reduction reactions, depending on physiological environment. The
      biochemical changes that accompany cancer alter physiological environment,
      enabling ruthenium complexes to be selectively activated in cancer tissues. Due
      to differing ligand geometry between their complexes, ruthenium compounds bind to
      DNA affecting its conformation differently than cisplatin and its analogues. In
      addition, non-nuclear targets, such as the mitochondrion and the cell surface,
      have also been implicated in the antineoplastic activity of some ruthenium
      complexes. Thus, ruthenium compounds offer the potential over antitumor
      platinum(II) complexes currently used in the clinic of reduced toxicity, a novel
      mechanism of action, the prospect of non-cross-resistance and a different
      spectrum of activity. In other words, some chemical properties make ruthenium
      compounds well suited for medicinal applications and as an alternative to
      platinum antitumor drugs in the treatment of cancer cells resistant to cisplatin.
      Although the pharmacological target for antitumor ruthenium compounds has not
      been unequivocally identified, there is a large body of evidence indicating that
      the cytotoxicity of many ruthenium complexes correlates with their ability to
      bind DNA although few exceptions have been reported. This review summarizes
      results demonstrating that several ruthenium compounds that exhibit antitumor
      effects different from cisplatin or its analogues bind DNA and modify it
      differently than cisplatin or its analogues.

PMID- 16790364
TI  - Regulation of T:B cell interactions by the inducible costimulator molecule: does
      ICOS "induce" disease?
AB  - The Inducible Costimulator molecule (ICOS), a member of the CD28 family of
      costimulatory molecules, was identified in 1999 as a molecule expressed primarily
      on activated human T cells. Induced upon activation, ICOS appears to be an ideal
      target for modifying T-cell-mediated immune responses. ICOS was also found to be
      highly expressed on germinal center T cells, suggesting that ICOS was involved in
      T:B cell interactions. While ICOS has subsequently been shown to be important for
      both Th1 and Th2 cell activation and effector function, a central role for ICOS
      in the generation and maintenance of humoral immunity is emerging. In this
      review, we summarize the evidence that the level of ICOS expression regulates T
      cell-dependent B cell responses and propose a model for the role of ICOS in
      diseases characterized by dysregulated humoral immunity.

PMID- 16790366
TI  - A novel function of DNA repair molecule Nbs1 in terminal differentiation of the
      lens fibre cells and cataractogenesis.
AB  - The Nbs1 protein, hypomorphic mutant in Nijmegen breakage syndrome (NBS), is a
      component of the Mre11/Rad50/Nbs1 (M/R/N) complex that acts as a DNA double
      strand break sensor and functions in cell cycle checkpoint in response to DNA
      damage and DNA repair. Here we report that targeted disruption of murine NBS1
      gene (Nbn) in the lens alters the M/R/N complex nuclear localization and results
      in microphthalmia in mice due to reduced proliferation of the lens epithelial
      cells. Unexpectedly, all Nbn-deficient lenses develop cataracts at an early age
      due to altered lens fibre cell differentiation, including disruption of normal
      lens epithelial and fibre cell architecture and incomplete denucleation of fibre
      cells, and these changes are independent of the p53 pathway. In addition, Nbn
      deficient lenses show dysregulated transcription of various crystallins. Thus,
      this study implicates a novel function of Nbs1 in terminal differentiation of the
      lens fibre cells and in cataractogenesis.

PMID- 16790365
TI  - Protective regulatory T cell generation in autoimmune diabetes by DNA
      covaccination with islet antigens and a selective CTLA-4 ligand.
AB  - DNA vaccination of autoimmune diabetes-prone NOD mice with unmodified target
      islet antigens, i.e., preproinsulin (PPIns) or glutamic acid decarboxylase 65
      (GAD65), is poorly protective. However, in this study, we demonstrate protection
      against disease by covaccination with a mutant B7-1 molecule (B7-1wa) that binds
      the negative T cell regulator CTLA-4 (CD152), but not CD28. Codelivery of
      plasmids encoding a PPIns-GAD65 fusion construct and B7-1wa protected against
      both insulitis and diabetes. In vitro, the T cells of covaccinated mice had
      negative responses to both insulin and GAD65, and this was restored by adding
      blocking antibodies to transforming growth factor beta1 (TGF-beta1), suggesting a
      role for this cytokine. Adoptive transfer experiments revealed that DNA
      vaccination generated protective CD4(+) regulatory T cells (Tr) of either CD25(+)
      or CD25(-) phenotype. Furthermore, vaccinated mice had increased numbers of T
      cells with Tr-associated markers, such as CTLA-4, Foxp3, and membrane-bound TGF
      beta1. Tr cells inhibited the responses of diabetogenic T cells to islet
      antigens, and depletion of T cells expressing membrane-bound TGF-beta1 abolished
      the suppressive effect. Thus, selective engagement of CTLA-4 during islet-antigen
      DNA vaccination induces Tr cells that protect against this autoimmune disease.

PMID- 16790367
TI  - Towards zero prevalence of chronic Pseudomonas aeruginosa infection in children
      with cystic fibrosis.
AB  - BACKGROUND: Data from the Belgian Cystic Fibrosis Registry consistently show that
      in one of the seven reference centres, the prevalence of Pseudomonas aeruginosa
      is half that observed at the national level. OBJECTIVES: To report the
      characteristics of non-transplanted patients in this clinic at the end of 2003,
      with special focus on paediatric patients. To describe and discuss our policy of
      inhaled antibiotic therapy. FINDINGS: The prevalence of P. aeruginosa among 116
      patients is 20.7%. The chronic colonization rate is 19.8% but only 2.8% in
      patients aged under 18 (n=72). Serologic data strongly support these results.
      Most paediatric patients (95%) are prescribed inhaled antibiotics, at least on an
      intermittent basis but the mean number of days of intravenous antibiotic
      treatment is four times lower than in other CF children in Belgium. 70% of
      children have an FEV1> or =90% predicted. DISCUSSION: We have reported a
      distinctly low rate of chronic colonization by P. aeruginosa in a cohort of CF
      children and suspect that a strategy of early, often <<prophylactic>> use of
      inhaled antibiotics, progressively implemented for over 15 years has
      substantially contributed to these results. Given the major impact of chronic P.
      aeruginosa colonization on prognosis in CF, it is suggested that a large
      prospective study of this approach is warranted.

PMID- 16790368
TI  - Sleep apnoea inducing hypoxemia is associated with early signs of carotid
      atherosclerosis in males.
AB  - The intima-media thickness (IMT) of carotid arteries as a marker of preclinical
      atherosclerosis was measured by ultrasonography in 49 subjects to determine, how
      strongly the obstructive sleep apnoea (OSA) syndrome is associated with
      atherosclerosis. Maximal IMT was higher in patients with cardiovascular diseases
      and with or without risk factors of atherosclerosis, presenting also OSA (apnoea
      hypopnoea index=26.1+/-15.6/h) compared to controls without OSA (0.91+/-0.21 mm
      versus 0.77+/-0.18 mm, p<0.05). The prevalence of IMT > or = 0.85 mm was also
      higher in patients with cardiovascular pathology presenting OSA than without it
      (p<0.05). IMT(max) was increased in subjects with mild to moderate OSA alone
      (AHI=20.4+/-8.7/h) versus healthy controls (0.83+/-0.14 mm versus 0.63+/-0.08 mm,
      p<0.01). Regression analysis revealed a correlation of IMT(max) with the
      frequency, intensity and duration of intermittent hypoxemia reflected by AHI
      (p<0.01), minimal oxygen saturation (p<0.01) and time spent with Sa(O2) < 90%
      (p<0.05) in patients presenting OSA. The results indicate clear association
      between early signs of carotid atherosclerosis and moderate OSA in males with and
      without concomitant cardiovascular pathology.

PMID- 16790369
TI  - Two-step purification of scutellarin from Erigeron breviscapus (vant.) Hand.
      Mazz. by high-speed counter-current chromatography.
AB  - Scutellarin, a flavone glycoside, popularly applied for the treatment of
      cardiopathy, has been purified in two-step purification by high-speed counter
      current chromatography (HSCCC) from Erigeron breviscapus (vant.) Hand. Mazz.
      (Deng-zhan-hua in Chinese), a well-known traditional Chinese medicinal plant for
      heart disease. Two solvent systems, n-hexane-ethyl acetate-methanol-acetic acid
      water (1:6:1.5:1:4, v/v/v/v/v) and ethyl acetate-n-butanol-acetonitrile-0.1% HCl
      (5:2:5:10, v/v/v/v) were used for the two-step purification. The purity of the
      collected fraction of scutellarin was 95.6%. This study supplies a new
      alternative method for purification of scutellarin.

PMID- 16790370
TI  - Efficient purification and preconcentration of erythropoietin in human urine by
      reusable immunoaffinity column.
AB  - In this paper, an efficient method is proposed for purification and
      preconcentration of erythropoietin (EPO) in human urine samples. The EPO-specific
      immunoaffinity column (IAC) was generated by covalent immobilization of anti-EPO
      polyclonal antibodies on Sepharose 4B support. The EPO-binding capacity of the
      IAC was found to be about 2.0 microg (6.6IU) per 1.5 mL of gel and the activity
      recoveries of EPO at low concentrations of 7.8, 10 and 120 m IU/mL by the IAC
      were between 78 and 86%. Substantial cleanup effect was observed when the IAC was
      applied to human urine samples.

PMID- 16790372
TI  - Increasing sex difference in bone strength in old age: The Age, Gene/Environment
      Susceptibility-Reykjavik study (AGES-REYKJAVIK).
AB  - INTRODUCTION: It is important to identify possible pathological mechanisms that
      underlie the known sexual dimorphism in bone fragility in old age. In this cross
      sectional population-based study, we use data from three different skeletal sites
      to examine sex differences in volumetric bone density, geometry and strength
      indices and determine whether sex differences in these bone strength measures
      continue to increase into very old age. MATERIALS AND METHODS: A total of 1715
      elderly individuals (807 men and 908 women) age 67-93 years, participants in a
      population-based study, the Age, Gene/Environment Susceptibility-Reykjavik Study
      (AGES-REYKJAVIK) and not taking medications affecting bone metabolism, were
      studied. Quantitative computed tomography (QCT) was performed in the lumbar
      spine, hip and mid-femoral shaft to estimate volumetric trabecular, cortical and
      integral BMD, bone geometry and bone strength indices. Regression models were
      used to assess the effects of age and gender-adjustment for standing midlife
      height and current weight. RESULTS: At age 67-69 years, men had 24.9-31.7% larger
      cross-sectional bone size at measured sites than women. At all bone sites, women
      had two- to fivefold diminution in net bone mass with age compared to men but had
      comparable increments in bone size (1.8-6.0% per 10 years). This was reflected in
      significantly worse (more than twofold) bone strength measures with age in women,
      including compressive strength indices at the spine, femoral neck and trochanter
      and bending strength indices at the femoral neck. CONCLUSION: With the
      limitations of a cross-sectional study, our data support the hypothesis that sex
      differences in bone strength continue into old age. These sex differences appear
      to be due to greater net bone loss in women rather than due to greater bone gain
      in men.

PMID- 16790371
TI  - Association of obesity, serum glucose and lipids with the risk of advanced
      colorectal adenoma and cancer: a case-control study in Korea.
AB  - BACKGROUND: Previous studies on colorectal cancer risk suggest that obesity,
      serum lipids and glucose might be related to colorectal carcinogenesis. This case
      control study was conducted to investigate the association between obesity, serum
      lipids and glucose, and the risk of advanced colorectal adenoma and cancer.
      METHODS: Patients with histologically confirmed colorectal cancers (n=105), same
      number of patients with advanced colorectal adenomas matched by age and sex, and
      the same number of controls matched by age and sex were selected in Hanyang
      University Guri Hospital between January 2002 and June 2004. RESULTS: Adenoma and
      cancer group showed significantly higher levels of mean body mass index and serum
      glucose. Cancer group also showed significantly lower mean serum lipids levels
      than controls. We used an unordered polytomous logistic model to calculate
      multivariate odds ratios for advanced adenoma and cancer relative to controls.
      Higher serum glucose level was more strongly associated with increased risk of
      cancer relative to controls (odds ratio, 3.0; 95% confidence interval, 0.9-9.8)
      than with increased risk of advanced adenoma (odds ratio, 2.1; 95% confidence
      interval, 0.9-5.4). Higher body mass index was strongly associated with increased
      risk of advanced adenoma (odds ratio, 10.8; 95% confidence interval, 4.6-25.3),
      but associated with attenuated risk of cancer (odds ratio, 2.3; 95% confidence
      interval, 0.9-5.8). Serum triglycerides and cholesterol levels were strongly
      associated with reduced risk of cancer (odds ratio, 0.3; 95% confidence interval,
      0.1-0.8 and odds ratio, 0.2; 95% confidence interval, 0.1-0.6, respectively).
      CONCLUSIONS: Obesity and hyperglycaemia are positively related to advanced
      colorectal adenoma formation. Furthermore, hyperglycaemia plays an important role
      in progression to cancer. Findings on an inverse relationship between serum
      triglyceride and cholesterol levels and the risk of colorectal cancer may be the
      secondary results from metabolic or nutritional changes in advanced colorectal
      cancer patients and should be clarified in further studies.

PMID- 16790373
TI  - Germany scores own goal on measles.

PMID- 16790374
TI  - Compromising comprehensive AIDS management will lead to failure.

PMID- 16790375
TI  - Evaluating a model for monitoring the virological efficacy of antiretroviral
      treatment in resource-limited settings.

PMID- 16790377
TI  - Meticillin-resistant Staphylococcus aureus in rural Asia.

PMID- 16790379
TI  - The Lancet forum on preparing for pandemic influenza.

PMID- 16790378
TI  - Where to begin human papillomavirus vaccination?

PMID- 16790380
TI  - Vaccination and the placebo effect.

PMID- 16790381
TI  - Streptococcus pneumoniae in western Europe: serotype distribution and incidence
      in children less than 2 years old.
AB  - We did a systematic search and synthesis of evidence on the incidence of invasive
      pneumococcal disease, symptomatic disease, and circulating Streptococcus
      pneumoniae serotypes in western Europe. Using data from studies published between
      1992 and 2005 we calculated a weighted mean invasive pneumococcal disease and
      pneumococcal meningitis incidence rate per 100,000 children aged 2 years or
      younger within 95% confidence intervals, together with the prevalence of S.
      pneumoniae serotypes and resistance to penicillin. Invasive pneumococcal disease
      incidence was 27.03 cases per 100,000 children under 2 years (95% CI 21.85-33.43)
      [corrected] Heptavalent conjugate vaccine serotypes account for 43.18-75.32% of
      isolates among people aged under 18 years of age. 11% of isolates in individuals
      aged under 18 years were penicillin resistant. The incidence of invasive
      pneumococcal disease appeared consistently lower in western European countries
      compared with studies from the USA. Thus the use of studies of vaccine
      effectiveness based on the US population may lead to an overestimation of the
      benefits of its introduction in Europe.

PMID- 16790382
TI  - Schistosomiasis and water resources development: systematic review, meta
      analysis, and estimates of people at risk.
AB  - An estimated 779 million people are at risk of schistosomiasis, of whom 106
      million (13.6%) live in irrigation schemes or in close proximity to large dam
      reservoirs. We identified 58 studies that examined the relation between water
      resources development projects and schistosomiasis, primarily in African
      settings. We present a systematic literature review and meta-analysis with the
      following objectives: (1) to update at-risk populations of schistosomiasis and
      number of people infected in endemic countries, and (2) to quantify the risk of
      water resources development and management on schistosomiasis. Using 35 datasets
      from 24 African studies, our meta-analysis showed pooled random risk ratios of
      2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among
      people living adjacent to dam reservoirs. The risk ratio estimate for studies
      evaluating the effect of irrigation on urinary schistosomiasis was in the range
      0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the
      range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed
      important spatial differences, idiosyncratic to the type of water resources
      development. We conclude that the development and management of water resources
      is an important risk factor for schistosomiasis, and hence strategies to mitigate
      negative effects should become integral parts in the planning, implementation,
      and operation of future water projects.

PMID- 16790383
TI  - Ventricular assist device-related infections.
AB  - Heart failure is a leading cause of death in developed nations despite medical
      management. Cardiac transplantation is a potentially lifesaving intervention for
      approximately 4000 advanced heart failure patients per year; however, the demand
      for donor hearts far exceeds the supply. Ventricular assist devices provide
      temporary support for patients with severe heart failure until myocardial
      recovery occurs or a donor heart becomes available. For those ineligible for
      transplantation, ventricular assist devices may be used permanently and have
      demonstrated reduced mortality and an improved quality of life compared with
      continued medical therapy. Nonetheless, these devices are under-used, in part due
      to the frequency of complications. Device-related infections are one of the most
      frequent sequelae of ventricular assist device placement and occur in 18-59% of
      cases. Infections can involve any part of the device and confer substantial
      morbidity and mortality. Here, we provide an introduction to ventricular assist
      devices, explore the nature and pathogenesis of ventricular assist device-related
      infections, discuss problems with diagnosis, and present treatment and prevention
      strategies.

PMID- 16790384
TI  - Obesity and infection.
AB  - Obesity increases morbidity and mortality through its multiple effects on nearly
      every human system. However, the various aspects of the association between
      obesity and infection have not been reviewed. Thus, we reviewed the relevant
      literature focusing on clinical aspects of this association. Obesity has a clear
      but not yet precisely defined effect on the immune response through a variety of
      immune mediators, which leads to susceptibility to infections. Data on the
      incidence and outcome of specific infections, especially community-acquired
      infections, in obese people are so far limited. The available data suggest that
      obese people are more likely than people of normal weight to develop infections
      of various types including postoperative infections and other nosocomial
      infections, as well to develop serious complications of common infections. Large
      prospective studies are required to further define the burden of infectious
      morbidity and mortality conferred by obesity.

PMID- 16790385
TI  - Tuberculosis-associated haemophagocytic syndrome.
AB  - Haemophagocytic syndrome is a disorder characterised by fevers, lymphadenopathy,
      hepatosplenomegaly, cytopenias, and hyperferritinaemia due to dysregulated
      activation and proliferation of macrophages, leading to uncontrolled phagocytosis
      of platelets, erythrocytes, lymphocytes, and their haematopoietic precursors
      throughout the reticuloendothelial system. Primary or familial haemophagocytic
      syndrome appears to have a genetic aetiology, whereas secondary haemophagocytic
      syndrome may be associated with malignancy, autoimmune disease, or infection.
      Epstein-Barr virus is the most common infectious aetiology implicated in
      haemophagocytic syndrome, but the syndrome has been associated with a variety of
      other viral, bacterial, and parasitic pathogens. We describe a case of
      haemophagocytic syndrome associated with disseminated Mycobacterium tuberculosis.
      We review all cases of M tuberculosis-associated haemophagocytic syndrome
      reported in the English language literature and discuss important issues
      pertaining to the epidemiology, diagnosis, and management of this disease.

PMID- 16790386
TI  - Rapid text referral.

PMID- 16790387
TI  - Necrotising fasciitis with Escherichia coli.

PMID- 16790388
TI  - Older adolescents and young adults with cancer: a different subset of patients?

PMID- 16790389
TI  - Patient associations, a social-sanitary reality.

PMID- 16790390
TI  - The Spanish Group of Medical Neuro-Oncology. GENOM.

PMID- 16790391
TI  - Molecular biology in colorectal cancer.
AB  - Cancer is a genetic disease. Colorectal cancer is probably the type of cancer for
      which the most is known about the genes affected by cancer-causing mutations,
      their normal functions and their carcinogenic effects when mutated. Most cancer
      causing mutations are somatic, occurring in the affected tissue during the course
      of carcinogenesis. However, most cancers also have a hereditary component that is
      caused by predisposing mutations that affect the germline, are heritable and
      contribute to the initiation of carcinogenesis. High-penetrance mutations confer
      predisposition to colorectal cancer mainly in Lynch syndrome (which involves
      mutations in mismatch-repair genes) and in familial adenomatous polyposis (which
      involves mutations in the APC tumour suppressor). Together, these conditions
      account for 5% or less of all cases of colorectal cancer. Low-penetrance
      mutations account for a high proportion of all the attributable risk of
      colorectal cancer, in both familial and sporadic cases. These mutations are more
      difficult to identify, but mainly due to the implementation of association
      studies, are increasingly being detected and characterized. The identification of
      both high- and low-penetrance mutations contributes significantly to our
      understanding of the molecular genetic processes occurring in cancer. This
      understanding facilitates the development of therapeutic drugs and preventive
      strategies.

PMID- 16790392
TI  - Therapeutic opportunities to control tumor cell cycles.
AB  - Tumor cell proliferation is frequently associated to genetic or epigenetic
      alterations in key cell cycle regulators. Most human tumors deregulate this
      pathway to sustain proliferation with independence of external mitogenic factors.
      In addition, the alteration of cell cycle proteins may confer genomic instability
      that results in additional mutations in these tumor cells. The frequent
      alteration of the cell cycle in tumor cells has launched the identification for
      critical cell cycle regulators as anticancer targets. The inhibition of some cell
      cycle kinases such as cyclin-dependent kinases (CDKs) or the Aurora and Polo
      mitotic kinases is currently under study in several preclinical and clinical
      trials. Similarly, the clinical success of microtubule poisons such as taxol has
      promoted new applied research in mitosis regulation. Recent investigations have
      suggested new targets of interest including additional kinases, phosphatases and
      other mitotic regulators such as microtubule motor proteins (kinesins). Current
      research in this area will undoubtedly result in new and improved targeted
      therapies for cancer treatment.

PMID- 16790394
TI  - Gynecological characteristics related to breast cancer in pre and postmenopausal
      women.
AB  - BACKGROUND: The objective of this study was two fold: to identify gynecological
      characteristics that distinguish women diagnosed with early-stage breast cancer
      from those at more advanced stages; to identify distinguishing characteristics
      between premenopausal and postmenopausal women diagnosed with the same stage.
      POPULATION AND METHOD: 186 incident cases diagnosed with breast cancer were
      identified out of the 685 patients who were seen to in 2000-2001. The variables
      to be studied were obtained by means of a specific questionnaire which collected
      data concerning reproductive characteristics and contraceptive types. RESULTS:
      Significant differences in the mean age were found, since the early-stage group
      was younger (57.01+/-12.82 vs. 65.06+/-15.11). Characteristic factors found in
      pre-menopausal women were: early menopause, they either had no children or a
      single child, no breastfeeding practice and a more extensive use of
      contraceptives. Postmenopausal women presented more advanced stages, more
      pregnancies and less abortions. CONCLUSIONS: By taking the obtained results into
      consideration, it would be recommendable to bring forward the age at which women
      are to be included in early detection programmes, and to conduct a follow-up of
      those women who present such factors to favour an earlier diagnosis of the
      disease.

PMID- 16790393
TI  - Bioinformatics and cancer: an essential alliance.
AB  - Modern research in cancer has been revolutionized by the introduction of new high
      throughput methodologies such as DNA microarrays. Keeping the pace with these
      technologies, the bioinformatics offer new solutions for data analysis and, what
      is more important, it permits to formulate a new class of hypothesis inspired in
      systems biology, more oriented to blocks of functionally-related genes. Although
      software implementations for this new methodologies is new there are some options
      already available. Bioinformatic solutions for other high-throughput techniques
      such as array-CGH of large-scale genotyping is also revised.

PMID- 16790395
TI  - Quality of Life assessment through the EORTC questionnaires of locally advanced
      rectal cancer patients treated with preoperative chemo-radiotherapy.
AB  - PURPOSE: To assess the quality of life in a group of rectal cancer patients
      during the treatment period. MATERIAL AND METHODS: A sample of 83 rectal cancer
      patients in Dukes' stages B2 or C who started a chemoradiotherapy treatment
      followed by surgery, have filled in the EORTC core questionnaire QLQC30 and the
      colorectal module QLQ-CR38, in three moments during the treatment and follow-up
      periods: at the beginning of the treatment, at the end of the chemoradiotherapy,
      and after surgery. Clinical and demographic data have also been recorded. Quality
      of Life scores and changes in them among the three assessments have been
      calculated. RESULTS: Quality of life scores of patients who have followed the
      treatment has been good in most dimensions, and has shown similar to the clinical
      data. Soft and moderate alterations have appeared in the areas of disease
      symptoms, treatment toxicity, fatigue, emotional and sexual functioning, and also
      in functional areas after surgery. Quality of life has been stable or has had
      small changes in most dimensions. A worsening in toxicity areas has appeared
      after the neoadyuvant treatment. After surgery there has been a worsening in
      functional areas, fatigue and appetite loss, and an improvement in diarrhoea.
      CONCLUSIONS: Quality of life scores and clinical data indicate that the situation
      of the patients who have received the treatments has been good. Patients under
      treatment stood it adequately.

PMID- 16790396
TI  - Results of radiotherapy in primary cutaneous lymphoma.
AB  - INTRODUCTION: Multiple therapeutic strategies have been proposed for the
      management of primary cutaneous lymphomas. We report the outcome data and
      therapeutic response of a group of patients treated with local radiotherapy.
      MATERIAL AND METHODS: Twenty seven patients with diagnostic of cutaneous lymphoma
      and treated with local radiation were evaluated for clinical response. Thirteen
      cases corresponded to cutaneous T-cell lymphomas (CTCL) and 14 to cutaneous B
      cell lymphomas (CBCL). Orthovoltage radiotherapy of 100 Kv was used and total
      dose of radiation ranged from 15 to 30 Gy (mean 24 Gy; median 20 Gy). RESULTS:
      The immediate response to the treatment was satisfactory in all cases. In 24
      patients (89%) complete response was obtained in the irradiated lesion and in 3
      cases (11%) the response was partial. With a mean follow-up of 25.4 months (range
      1-100 months) the overall response rate was 96.3%. Fourteen patients (52%) were
      alive without evidence of disease (6 CTCL and 8 CBCL), 5 patients (18%) retained
      cutaneous disease or had systemic progression (3 CTCL and 2 CBCL) and 8 patients
      died (30%). In 7 patients lymphoma progression was the factor leading to death
      (26%) and in one patient the cause was not related with the disease. CONCLUSIONS:
      Radiotherapy was demonstrated to be able to induce clinical remission of primary
      cutaneous lymphomas.

PMID- 16790397
TI  - Medullary thyroid carcinoma: multivariate analysis of prognostic factors
      influencing survival.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare development of thyroid
      cancer with a no negligible mortality rate. Our aim was to determine factors that
      predict outcome in patients with MTC. METHODS: We reviewed the records of all
      patients with MTC (n=56) who underwent treatment at our institution between
      January 1990 and December 2000. Univariate and multivariate analysis of
      clinicopathologic predictors of MTC outcome were performed to identify subsets of
      patients with different probabilities in terms of overall survival, local
      recurrence, and distant metastases. RESULTS: Multivariate analysis demonstrated
      that a statistically significant decrease in overall survival is associated with
      T4b tumours (p=0.06), the presence of distant metastases at the time of
      presentation (p=0.033), lymphatic invasion (p=0.099), and postoperative treatment
      (p=0.045). CONCLUSIONS: The analysis of survival curves of patients with MTC
      shows that the occurrence of locoregional and distant metastases occurs
      preferentially within the first 5 years, which identifies this as a crucial
      period for follow-up. In this series of patients with MTC, the tumours classified
      as T4b, metastases at presentation, the presence of lymphovascular invasion, and
      postoperative treatment were the most important prognostic features. At present,
      there is no available beneficial adjuvant therapy. However, as the development of
      molecular therapy progresses, it should be tested in clinical trials with the
      purpose of achievement of novel targeted therapies for selected MTC patients with
      risk factors.

PMID- 16790398
TI  - "Juvenile" oncology--a missing subspecialty. The experience of a reference cancer
      centre.
AB  - INTRODUCTION: Despite unique tumor epidemiology and a higher cancer incidence
      compared to pediatric patients, adolescents and young adults have not been
      receiving specialized, multidisciplinary, centralized care. In an effort to
      emphasize this need, we present outcome and toxicity data from a reference
      centre. METHODS: Cohort of 150 patients aged 15-30 treated for malignant tumors
      of lymphoid and solid organs from 1986 to 2002. RESULTS: Patients aged 15-19
      commonly had lymphomas, germ cell tumors and pediatric sarcomas, whereas those
      aged 20-30 experienced germ cell tumors, lymphomas, melanomas and epithelial
      tumors more often. Overall 5- and 10-year survival was 80%, whereas 5-year and 10
      year time to treatment failure was 68% and 43.5% respectively. 24% of patients
      experienced persistent, late treatment-related toxicities that interfered with
      their normal lifestyle. CONCLUSION: Despite the need for specialized care,
      psychosocial support and enrollment in clinical trials, youngsters have not been
      recognized as a patient group with distinct needs. Development of "Juvenile"
      oncology is required.

PMID- 16790399
TI  - Primary Hodgkin's lymphoma of the caecum.
AB  - Extra-nodal Hodgkin's lymphoma (HL) represents 15% of all Hodgkin's lymphomas;
      the primary intestinal site accounts for 1% and with involvement of the ascending
      colon being rare. We present the case of a patient of 62 years of age diagnosed
      as having acute appendicitis. Anatomopathology on the excised appendectomy tissue
      indicated nodular lymphocytic predominant Hodgkin's lymphoma (NLPHL). The
      morphology indicated isolated L&H (lymphocytic or histiocytic) cells or in
      groups, surrounded by T lymphocytes, in an environment of germinal centres
      together with phenomena that would be interpreted as progressive transformation.
      Immunohistochemistry staining of the HL cells were positive for CD45, CD20, Bc16,
      EMA and MUM1 and negative for CD15 and CD30. No complementary treatment was
      administered. Following a literature search, the present case would appear to be
      the first of its kind.

PMID- 16790400
TI  - Disseminated retroperitoneal choriocarcinoma with open fistula to intestine.
      "Restitutio ad integrum" with chemotherapy alone.
AB  - We hereby present a clinical case of a germinal tumour with a pulmonary and
      retroperitoneal dissemination in form of a great adenopathic mass that fistulizes
      into the duodenum, that obtained a complete resolution with chemotherapy.

PMID- 16790401
TI  - Diagnosis of a primary testicular lymphoma by echography and magnetic resonance
      imaging.
AB  - We here describe a primary large B cell non-Hodgkin lymphoma of the right
      testicle in a 73-year-old male diagnosed with echography and magnetic resonance
      imaging. Treatment was based upon orchiectomy and chemotherapy, without any
      recurrence 2 years later. Ultrasonography and magnetic resonance findings with
      normal serum tumoural markers (AFP and B-HCG) can differentiate these tumors from
      germinal testicular tumors.

PMID- 16790402
TI  - Intramedullary metastases due to non microcytic lung carcinoma.

PMID- 16790403
TI  - Sustainable pest regulation in agricultural landscapes: a review on landscape
      composition, biodiversity and natural pest control.
AB  - Agricultural intensification has resulted in a simplification of agricultural
      landscapes by the expansion of agricultural land, enlargement of field size and
      removal of non-crop habitat. These changes are considered to be an important
      cause of the rapid decline in farmland biodiversity, with the remaining
      biodiversity concentrated in field edges and non-crop habitats. The
      simplification of landscape composition and the decline of biodiversity may
      affect the functioning of natural pest control because non-crop habitats provide
      requisites for a broad spectrum of natural enemies, and the exchange of natural
      enemies between crop and non-crop habitats is likely to be diminished in
      landscapes dominated by arable cropland. In this review, we test the hypothesis
      that natural pest control is enhanced in complex patchy landscapes with a high
      proportion of non-crop habitats as compared to simple large-scale landscapes with
      little associated non-crop habitat. In 74% and 45% of the studies reviewed,
      respectively, natural enemy populations were higher and pest pressure lower in
      complex landscapes versus simple landscapes. Landscape-driven pest suppression
      may result in lower crop injury, although this has rarely been documented.
      Enhanced natural enemy activity was associated with herbaceous habitats in 80% of
      the cases (e.g. fallows, field margins), and somewhat less often with wooded
      habitats (71%) and landscape patchiness (70%). The similar contributions of these
      landscape factors suggest that all are equally important in enhancing natural
      enemy populations. We conclude that diversified landscapes hold most potential
      for the conservation of biodiversity and sustaining the pest control function.

PMID- 16790404
TI  - Avian influenza H5N1 in viverrids: implications for wildlife health and
      conservation.
AB  - The Asian countries chronically infected with avian influenza A H5N1 are 'global
      hotspots' for biodiversity conservation in terms of species diversity, endemism
      and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally
      infected and killed a range of wild bird species, four felid species and a
      mustelid. Here, we report fatal disseminated H5N1 infection in a globally
      threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that
      avian influenza H5N1 poses to mammalian and avian biodiversity across its
      expanding geographic range.

PMID- 16790406
TI  - Scale-free foraging by primates emerges from their interaction with a complex
      environment.
AB  - Scale-free foraging patterns are widespread among animals. These may be the
      outcome of an optimal searching strategy to find scarce, randomly distributed
      resources, but a less explored alternative is that this behaviour may result from
      the interaction of foraging animals with a particular distribution of resources.
      We introduce a simple foraging model where individual primates follow mental maps
      and choose their displacements according to a maximum efficiency criterion, in a
      spatially disordered environment containing many trees with a heterogeneous size
      distribution. We show that a particular tree-size frequency distribution induces
      non-Gaussian movement patterns with multiple spatial scales (Levy walks). These
      results are consistent with field observations of tree-size variation and spider
      monkey (Ateles geoffroyi) foraging patterns. We discuss the consequences that our
      results may have for the patterns of seed dispersal by foraging primates.

PMID- 16790405
TI  - The evolution of hexapod engrailed-family genes: evidence for conservation and
      concerted evolution.
AB  - Phylogenetic analyses imply that multiple engrailed-family gene duplications
      occurred during hexapod evolution, a view supported by previous reports of only a
      single engrailed-family gene in members of the grasshopper genus Schistocerca and
      in the beetle Tribolium castaneum. Here, we report the cloning of a second
      engrailed-family gene from Schistocerca gregaria and present evidence for two
      engrailed-family genes from four additional hexapod species. We also report the
      existence of a second engrailed-family gene in the Tribolium genome. We suggest
      that the engrailed and invected genes of Drosophila melanogaster have existed as
      a conserved gene cassette throughout holometabolous insect evolution. In total 11
      phylogenetically diverse hexapod orders are now known to contain species that
      possess two engrailed-family paralogues, with in each case only one paralogue
      encoding the RS-motif, a characteristic feature of holometabolous insect invected
      proteins. We propose that the homeoboxes of hexapod engrailed-family paralogues
      are evolving in a concerted fashion, resulting in gene trees that overestimate
      the frequency of gene duplication. We present new phylogenetic analyses using non
      homeodomain amino acid sequence that support this view. The S. gregaria engrailed
      family paralogues provide strong evidence that concerted evolution might in part
      be explained by recurrent gene conversion. Finally, we hypothesize that the RS
      motif is part of a serine-rich domain targeted for phosphorylation.

PMID- 16790407
TI  - Surplus nest boxes and the potential for polygyny affect clutch size and
      offspring sex ratio in house wrens.
AB  - Females of many species can gain benefits from being choosy about their mates and
      even exhibit context-dependent investment in reproduction in response to the
      quality of their breeding situation. Here, we show that if a male house wren is
      provided with surplus nest boxes in his territory, his mate lays a larger clutch
      with a significantly higher proportion of sons. This response to a territory
      characteristic directly associated with male competitive ability, and ultimately
      to male reproductive success, suggests that male competition over access to high
      quality territories with surplus nest boxes (i.e. those able to support polygyny)
      may influence female reproductive investment decisions. The results of this study
      have interesting implications, particularly considering the important role that
      studies of cavity nesting birds utilizing nest boxes have played in advancing our
      understanding of behaviour, ecology and evolution.

PMID- 16790408
TI  - Sex-specific development of cell-mediated immunity under experimentally altered
      rearing conditions in blue tit nestlings.
AB  - In birds, poor rearing conditions usually have negative effects on T-cell
      mediated immune response. However, earlier studies demonstrate that fitness
      related traits such as body mass may show sex-specific patterns when subject to
      alteration of rearing conditions. Therefore, to investigate whether deterioration
      of rearing conditions influences the development of immune function differently
      in male and female nestlings, we performed brood size manipulation experiments on
      blue tit (Parus caeruleus) nestlings. To alter rearing conditions, some broods
      were increased by three nestlings soon after hatching, while other broods were
      left non-manipulated. Immune response was assessed as a hypersensitivity reaction
      to phytohaemagglutinin in 11-day-old nestlings. Additionally, we studied the
      consequences of brood size manipulation for fledgling body mass and tarsus
      length. The enlargement of brood size had different effects on the cellular
      immune responses of male and female nestlings, with males being more negatively
      affected than their female nest-mates. Sex-specific effects of poor rearing
      conditions were also recorded for tarsus length, such that tarsus growth was more
      retarded in female than in male nestlings. We discuss the effects of
      deterioration of rearing conditions on sex-specific development of cell-mediated
      immunity with respect to sexual dimorphism of size and developmental strategies
      in male and female nestlings.

PMID- 16790409
TI  - Maternal effects due to male attractiveness affect offspring development in the
      zebra finch.
AB  - Maternal effects occur when offspring phenotype is influenced by environmental
      factors experienced by the mother. Mothers are predicted to invest differentially
      in offspring in ways that will maximize offspring fitness depending on the
      environment she expects them to encounter. Here, we test for maternal effects in
      response to mate attractiveness on offspring developmental traits in the zebra
      finch Taeniopygia guttata. We controlled for parental genetic quality by
      manipulating male attractiveness using coloured leg rings and by randomly
      assigning mating pairs. The potential confounding effect of differential nestling
      care was controlled for by cross-fostering clutches and by allowing for variance
      due to foster father attractiveness in general linear models. We found a
      difference in egg mass investment between attractiveness groups and, importantly,
      we found that all of the offspring traits we measured varied with the
      attractiveness of the father. This provides strong evidence for maternal effects
      in response to mate attractiveness. Furthermore, due to the experiment design, we
      can conclude that these effects were mediated by differential investment of egg
      resources and not due to genetic differences or differences in nestling care.

PMID- 16790410
TI  - Parasites shape the optimal investment in immunity.
AB  - The evolution of optimal functioning and maintenance of the immune system is
      thought to be driven by the costs arising from the allocation of resources to
      immune functions rather than to growth and reproduction and by the benefits
      arising from higher defence if an infection occurs. In young animals there is a
      high premium for fast growth and competitiveness and a parasite-mediated trade
      off is thus predicted between the allocation of resources to growth versus immune
      function. In a field study on nestling great tits (Parus major), we manipulated
      simultaneously the level of immune defence by a dietary supplementation of the
      immunostimulant methionine and ectoparasite (Ceratophyllus gallinae) abundance in
      the nest and thereby assessed both the costs and benefits of investing in immune
      defence. Nestlings supplemented with methionine grew slower during the
      experimental boost of their immune system compared to controls. Thereafter,
      however, nestlings with a boosted immune system grew at faster rates under
      parasite pressure compared to unstimulated birds. It experimentally shows the
      costs and benefits of investment in immunity and suggests that the evolution of
      optimum host defence is governed by a parasite-mediated allocation trade-off
      between growth and immune function.

PMID- 16790411
TI  - Species traits and the form of individual species-energy relationships.
AB  - Environmental energy availability explains much of the spatial variation in
      species richness at regional scales. While numerous mechanisms that may drive
      such total species-energy relationships have been identified, knowledge of their
      relative contributions is scant. Here, we adopt a novel approach to identify
      these drivers that exploits the composite nature of species richness, i.e. its
      summation from individual species distributions. We construct individual species
      energy relationships (ISERs) for each species in the British breeding avifauna
      using both solar (temperature) and productive energy metrics (normalized
      difference vegetation index) as measures of environmental energy availability. We
      use the slopes of these relationships and the resultant change in deviance,
      relative to a null model, as measures of their strength and use them as response
      variables in multiple regressions that use ecological traits as predictors. The
      commonest species exhibit the strongest ISERs, which is counter to the prediction
      derived from the more individuals hypothesis. There is no evidence that predatory
      species have stronger ISERs, which is incompatible with the suggestion that high
      levels of energy availability increase the length of the food chain allowing
      larger numbers of predators to exist. We find some evidence that species with
      narrow niche breadths have stronger ISERs, thus providing one of the few pieces
      of supportive evidence that high-energy availability promotes species richness by
      increasing the occurrence of specialist species that use a narrow range of
      resources.

PMID- 16790412
TI  - Aggressive behaviour affects selection on morphology by influencing settlement
      patterns in a passerine bird.
AB  - The importance of behaviours as instigators or inhibitors of evolutionary change
      remains largely unresolved and this is in part because there are very few
      empirical examples of how behaviours affect evolutionary processes. By
      determining the environment of breeding, aggressive interactions over territories
      have the potential to strongly impact selection pressures experienced by
      individuals. Western bluebirds (Sialia mexicana) provide a unique opportunity to
      investigate the evolutionary importance of aggression, since their highly
      variable breeding habitat favours distinct foraging techniques and they also
      compete aggressively for nest boxes, a resource that is easy to manipulate. Here,
      I show experimentally that more aggressive males compete more effectively for
      territories with a high density of nest boxes and, as a consequence, aggressive
      and non-aggressive males are sorted into distinct breeding habitats that differ
      in the strength of selection on morphological traits. Specifically, males with
      longer tails and tarsi were favoured in open habitats where high agility is
      required to forage efficiently, whereas in forested habitats, where agility is
      less important, selection was weak. These results show that aggression can affect
      selection on a local scale by determining individual settlement patterns. More
      generally, because territorial interactions are important across a wide variety
      of taxa, these results suggest that aggressive behaviour has the potential to
      impact the evolutionary trajectory of many animal populations.

PMID- 16790413
TI  - Monogamy in the maternally mouthbrooding Lake Tanganyika cichlid fish Tropheus
      moorii.
AB  - Supported by evidence for assortative mating and polygynandry, sexual selection
      through mate choice was suggested as the main force driving the evolution of
      colour diversity of haplochromine cichlids in Lakes Malawi and Victoria. The
      phylogenetically closely related tribe Tropheini of Lake Tanganyika includes the
      genus Tropheus, which comprises over 100 colour variants currently classified
      into six morphologically similar, polyphyletic species. To assess the potential
      for sexual selection in this sexually monochromatic maternal mouthbrooder, we
      used microsatellite-based paternity inference to investigate the mating system of
      Tropheus moorii. In contrast to haplochromines in Lake Malawi, multiple paternity
      is rare or even absent in broods of T. moorii. Eighteen of the 19 analysed
      families were consistent with genetic monogamy, while either a mutation or more
      than one sire explained the genotype of one offspring in another brood. We
      discuss the differences in breeding behaviour between T. moorii and the Lake
      Malawi haplochromines, and evaluate additional factors or alternatives to sexual
      selection as promoters of colour diversification. A preliminary survey of other
      Tropheini species suggested that multiple paternity is infrequent in the entire
      tribe.

PMID- 16790414
TI  - Mitochondrial diversity in European and Chinese pigs is consistent with
      population expansions that occurred prior to domestication.
AB  - Mitochondrial DNA (mtDNA) diversity in European and Asian pigs was assessed using
      1536 samples representing 45 European and 21 Chinese breeds. Diagnostic
      nucleotide differences in the cytochrome b (Cytb) gene between the European and
      Asian mtDNA variants were determined by pyrosequencing as a rapid screening
      method. Subsequently, 637bp of the hypervariable control region was sequenced to
      further characterize mtDNA diversity. All sequences belonged to the D1 and D2
      clusters of pig mtDNA originating from ancestral wild boar populations in Europe
      and Asia, respectively. The average frequency of Asian mtDNA haplotypes was 29%
      across European breeds, but varied from 0 to 100% within individual breeds. A
      neighbour-joining (NJ) tree of control region sequences showed that European and
      Asian haplotypes form distinct clusters consistent with the independent
      domestication of pigs in Asia and Europe. The Asian haplotypes found in the
      European pigs were identical or closely related to those found in domestic pigs
      from Southeast China. The star-like pattern detected by network analysis for both
      the European and Asian haplotypes was consistent with a previous demographic
      expansion. Mismatch analysis supported this notion and suggested that the
      expansion was initiated before domestication.

PMID- 16790415
TI  - Leg regeneration stunts wing growth and hinders flight performance in a stick
      insect (Sipyloidea sipylus).
AB  - Major morphological structures are sometimes produced not once, but twice. For
      example, stick insects routinely shed legs to escape a predator or tangled moult,
      and these legs are subsequently re-grown. Here, I show that in Sipyloidea
      sipylus, re-growth of a leg during development causes adults to have
      disproportionately smaller wings and increases wing loading. These morphological
      consequences of leg regeneration led to significant reductions in several
      biologically relevant measures of individual flight performance. This previously
      unrecognized tradeoff between legs and wings reveals the integrated nature of
      phasmid phenotypes, and I propose how this tradeoff may have shaped phasmid
      evolution.

PMID- 16790416
TI  - Division of labour and colony efficiency in social insects: effects of
      interactions between genetic architecture, colony kin structure and rate of
      perturbations.
AB  - The efficiency of social insect colonies critically depends on their ability to
      efficiently allocate workers to the various tasks which need to be performed.
      While numerous models have investigated the mechanisms allowing an efficient
      colony response to external changes in the environment and internal
      perturbations, little attention has been devoted to the genetic architecture
      underlying task specialization. We used artificial evolution to compare the
      performances of three simple genetic architectures underlying within-colony
      variation in response thresholds of workers to five tasks. In the 'deterministic
      mapping' system, the thresholds of individuals for each of the five tasks is
      strictly genetically determined. In the second genetic architecture
      ('probabilistic mapping'), the genes only influence the probability of engaging
      in one of the tasks. Finally, in the 'dynamic mapping' system, the propensity of
      workers to engage in one of the five tasks depends not only on their own
      genotype, but also on the behavioural phenotypes of other colony members. We
      found that the deterministic mapping system performed well only when colonies
      consisted of unrelated individuals and were not subjected to perturbations in
      task allocation. The probabilistic mapping system performed well for colonies of
      related and unrelated individuals when there were no perturbations. Finally, the
      dynamic mapping system performed well under all conditions and was much more
      efficient than the two other mapping systems when there were perturbations.
      Overall, our simulations reveal that the type of mapping between genotype and
      individual behaviour greatly influences the dynamics of task specialization and
      colony productivity. Our simulations also reveal complex interactions between the
      mode of mapping, level of within-colony relatedness and risk of colony
      perturbations.

PMID- 16790417
TI  - Host mating system and the prevalence of disease in a plant population.
AB  - A modified susceptible-infected-recovered (SIR) host-pathogen model is used to
      determine the influence of plant mating system on the outcome of a host-pathogen
      interaction. Unlike previous models describing how interactions between mating
      system and pathogen infection affect individual fitness, this model considers the
      potential consequences of varying mating systems on the prevalence of resistance
      alleles and disease within the population. If a single allele for disease
      resistance is sufficient to confer complete resistance in an individual and if
      both homozygote and heterozygote resistant individuals have the same mean birth
      and death rates, then, for any parameter set, the selfing rate does not affect
      the proportions of resistant, susceptible or infected individuals at equilibrium.
      If homozygote and heterozygote individual birth rates differ, however, the mating
      system can make a difference in these proportions. In that case, depending on
      other parameters, increased selfing can either increase or decrease the rate of
      infection in the population. Results from this model also predict higher
      frequencies of resistance alleles in predominantly selfing compared to
      predominantly outcrossing populations for most model conditions. In populations
      that have higher selfing rates, the resistance alleles are concentrated in
      homozygotes, whereas in more outcrossing populations, there are more resistant
      heterozygotes.

PMID- 16790418
TI  - Telonemia, a new protist phylum with affinity to chromist lineages.
AB  - Recent molecular investigations of marine samples taken from different
      environments, including tropical, temperate and polar areas, as well as deep
      thermal vents, have revealed an unexpectedly high diversity of protists, some of
      them forming deep-branching clades within important lineages, such as the
      alveolates and heterokonts. Using the same approach on coastal samples, we have
      identified a novel group of protist small subunit (SSU) rDNA sequences that do
      not correspond to any phylogenetic group previously identified. Comparison with
      other sequences obtained from cultures of heterotrophic protists showed that the
      environmental sequences grouped together with Telonema, a genus known since 1913
      but of uncertain taxonomic affinity. Phylogenetic analyses using four genes (SSU,
      Hsp90, alpha-tubulin and beta-tubulin), and accounting for gamma- and covarion
      distributed substitution rates, revealed Telonema as a distinct group of species
      branching off close to chromist lineages. Consistent with these gene trees,
      Telonema possesses ultrastructures revealing both the distinctness of the group
      and the evolutionary affinity to chromist groups. Altogether, the data suggest
      that Telonema constitutes a new eukaryotic phylum, here defined as Telonemia,
      possibly representing a key clade for the understanding of the early evolution of
      bikont protist groups, such as the proposed chromalveolate supergroup.

PMID- 16790419
TI  - Bacteriophage-mediated competition in Bordetella bacteria.
AB  - Apparent competition between species is believed to be one of the principal
      driving forces that structure ecological communities, although the precise
      mechanisms have yet to be characterized. Here we develop a model system that
      isolates phage-mediated interactions by neutralizing resource competition with a
      large excess of nutrients, and consists of two genetically identical Bordetella
      strains that differ only in that one is the carrier of phage and the other is
      susceptible to the phage. We observe and quantify the competitive advantage of
      the bacterial strain bearing the prophage in both invading and in resisting
      invasion by the bacterial strain sensitive to the phage, and use our experimental
      measurements to develop a mathematical model of phage-mediated competition. The
      model predicts, and experimental evidence confirms, that the competitive
      advantage conferred by the lysogenic phage depends only on the phage pathology on
      the sensitive bacterial strain and is independent of other phage and host
      parameters, such as the infection-causing contact rate, the spontaneous and
      infection-induced lysis rates and the phage burst size. This work combines
      experimental and mathematical approaches to the study of phage-driven
      competition, and provides an experimentally tested framework for evaluation of
      the effects of pathogens/parasites on interspecific competition.

PMID- 16790420
TI  - Role of the Phox homology domain and phosphorylation in activation of serum and
      glucocorticoid-regulated kinase-3.
AB  - Serum and glucocorticoid-regulated kinases (SGKs) form a family of
      serine/threonine protein kinases that exhibit structural and sequence similarity
      to the protein kinase B (PKB)/Akt family. The major difference between these two
      families is the absence of a lipid-binding, pleckstrin homology domain in the
      SGKs. Despite the absence of the pleckstrin homology domain, activation of the
      three human isoforms is, like PKB, dependent upon the phosphatidylinositol 3'
      kinase (PI3K) pathway that is induced by growth factors and mitogens. Full-length
      SGK3 contains a complete Phox homology (PX) domain that targets the protein to
      endosomes. Both a functional PX domain and PI3K activation are necessary for
      phosphorylation of SGK3 at two regulatory sites (Thr-320 and Ser-486) and
      subsequent induction of kinase activity. PDK1 phosphorylates endosome-associated
      SGK3 at Thr-320, whereas diversion of SGK3 to the plasma membrane, where PDK1
      normally activates PKB, interferes with PDK1 phosphorylation of SGK3. A chimeric
      protein in which the carboxyl-terminal hydrophobic motif (HM) of SGK3 has been
      exchanged for the HM of PRK2 is constitutively active. Finally, we demonstrate
      that SGK3 activation becomes PX domain-independent once the HM is phosphorylated.
      Taken together, these data indicate that the targeting of SGK3 to endosomes,
      mediated by its PX domain, is essential for proper SGK3 activation, likely due to
      co-localization of SGK3 with an endosomal, PI3K-dependent and staurosporine
      sensitive HM kinase.

PMID- 16790422
TI  - Mechanism of instability in abortive cycling by T7 RNA polymerase.
AB  - Abortive transcription, the premature release of short transcripts 2-8 bases in
      length, is a unique feature of transcription, accompanying the transition from
      initiation to elongation in all RNA polymerases. The current study focuses on
      major factors that relate to the stability of initially transcribing abortive
      complexes in T7 RNA polymerase. Building on previous studies, results reveal that
      collapse of the DNA from the downstream end of the bubble is a major contributor
      to the characteristic instability of abortive complexes. Furthermore,
      transcription from a novel DNA construct containing a nick between positions -14
      and -13 of the nontemplate strand suggests that the more flexible promoter
      reduces somewhat the strain inherent in initially transcribing complexes, with a
      resulting decrease in abortive product release. Finally, as assessed by
      exonuclease III footprinting and transcription profiles, a DNA construct
      defective in bubble collapse specifically from the downstream end exhibits less
      abortive cycling and little perturbation of the final transition to elongation,
      including the process of promoter release.

PMID- 16790421
TI  - Conformational basis for SH2-Tyr(P)527 binding in Src inactivation.
AB  - Src protein-tyrosine kinase contains a myristoylation motif, a unique region, an
      Src homology (SH) 3 domain, an SH2 domain, a catalytic domain, and a C-terminal
      tail. The C-terminal tail contains a Tyr residue, Tyr527. Phosphorylation of
      Tyr527 triggers Src inactivation, caused by Tyr(P)527 binding to the SH2 domain.
      In this study, we demonstrated that a conformational contribution, not affinity,
      is the predominant force for the intramolecular SH2-Tyr(P)527 binding, and we
      characterized the structural basis for this conformational contribution. First, a
      phosphopeptide mimicking the C-terminal tail is an 80-fold weaker ligand than the
      optimal phosphopeptide, pYEEI, and similar to a phosphopeptide containing three
      Ala residues following Tyr(P) in binding to the Src SH2 domain. Second, the SH2
      Tyr(P)527 binding is largely independent of the amino acid sequence surrounding
      Tyr(P)527, and only slightly decreased by an inactivating mutation in the SH2
      domain. Furthermore, even the unphosphorylated C-terminal tail with the sequence
      of YEEI suppresses Src activity by binding to the SH2 domain. These experiments
      demonstrate that very weak affinity is sufficient for the SH2-Tyr(P)527 binding
      in Src inactivation. Third, the effective intramolecular SH2-Tyr(P)527 binding is
      attributed to a conformational contribution that requires residues Trp260 and
      Leu255. Although the SH3 domain is essential for Src inactivation by Tyr(P)527,
      it does not contribute to the SH2-Tyr(P)527 binding. These findings suggest a
      conformation-based Src inactivation model, which provides a unifying framework
      for understanding Src activation by a variety of mechanisms.

PMID- 16790423
TI  - Saccharomyces cerevisiae Hog1 protein phosphorylation upon exposure to bacterial
      endotoxin.
AB  - The yeast Hog1 protein is both functionally and structurally similar to the
      mammalian p38, belonging to the same family of mitogen-activated protein (MAP)
      kinases and responding to extracellular changes in osmolarity. Since p38 mediates
      lipopolysaccharide (LPS) effects in mammalian cells, we now tested the
      responsiveness of Hog1 upon exposure of the yeast Saccharomyces cerevisiae to
      bacterial LPS. In the presence of Escherichia coli LPS (100 ng/ml) and an
      endotoxically active, hexaacylated, synthetic lipid A (compound 506; 100 ng/ml),
      Hog1 becomes phosphorylated with a maximum of phosphorylation between 3 and 6 h,
      whereas a tetraacylated, inactive form of lipid A (compound 406) did not cause
      any modification in the phosphorylation state of Hog1. A triple labeling
      immunocytochemical study showed that phosphorylated Hog1 translocates into the
      nucleus after a 90-min incubation and becomes sparsely located in the cytoplasm.
      The translocation of the phospho-Hog1 is preceded by an increased expression of
      the HOG1 gene and concomitant with the expression of the Hog1 target gene, GPD1.
      We also observed that cells unable to synthesize Hog1 do not resist LPS as
      efficiently as wild-type cells. We conclude that the yeast S. cerevisiae is able
      to respond to the presence of Gram-negative bacteria endotoxin and that Hog1 is
      involved in this response.

PMID- 16790424
TI  - Identification of a novel class of nicotinic receptor antagonists: dimeric
      conotoxins VxXIIA, VxXIIB, and VxXIIC from Conus vexillum.
AB  - The venoms of predatory marine snails (Conus spp.) contain diverse mixtures of
      peptide toxins with high potency and selectivity for a variety of voltage-gated
      and ligand-gated ion channels. Here we describe the chemical and functional
      characterization of three novel conotoxins, alphaD-VxXIIA, alphaD-VxXIIB, and
      alphaD-VxXIIC, purified from the venom of Conus vexillum. Each toxin was observed
      as an approximately 11-kDa protein by LC/MS, size exclusion chromatography, and
      SDS-PAGE. After reduction, the peptide sequences were determined by Edman
      degradation chemistry and tandem MS. Combining the sequence data together with
      LC/MS and NMR data revealed that in solution these toxins are pseudo-homodimers
      of paired 47-50-residue peptides. The toxin subunits exhibited a novel
      arrangement of 10 conserved cystine residues, and additional post-translational
      modifications contributed heterogeneity to the proteins. Binding assays and two
      electrode voltage clamp analyses showed that alphaD-VxXIIA, alphaD-VxXIIB, and
      alphaD-VxXIIC are potent inhibitors of nicotinic acetylcholine receptors (nAChRs)
      with selectivity for alpha7 and beta2 containing neuronal nAChR subtypes. These
      dimeric conotoxins represent a fifth and highly divergent structural class of
      conotoxins targeting nAChRs.

PMID- 16790425
TI  - Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5
      transactivation domain.
AB  - NF-E2-related factor 2 (Nrf2) is the key transcription factor regulating the
      antioxidant response. Previous studies identified a nuclear localization signal
      (NLS) in the basic region and a nuclear exporting signal (NES) in the leucine
      zipper domain of Nrf2. In this study, we characterize a new functional NES
      (175LLSIPELQCLNI186) in the transactivation (TA) domain of Nrf2. A green
      fluorescence protein (GFP)-tagged Nrf2 segment (amino acids162-295) called GFP
      NESTA exhibited a cytosolic distribution that could be disrupted by L184A
      mutation or leptomycin B treatment. Chimeric expression of this NESTA with a
      nuclear protein GAL4DBD could expel GAL4DBD into the cytoplasm. A variety of
      oxidants, including sulforaphane, tert-butylhydroquinone, and H2O2, could
      effectively induce nuclear translocation of GFP-NESTA. Mutational studies showed
      that cysteine 183 may mediate the redox response of NESTA. The discovery of
      multiple NLS/NES motifs in Nrf2 and the redox sensitivity of NESTA imply Nrf2 may
      be self-sufficient to sense and transduce oxidative signals into the nucleus,
      consequently initiating antioxidant gene transcription.

PMID- 16790426
TI  - Conserved sequence box II directs transcription termination and primer formation
      in mitochondria.
AB  - The human mitochondrial transcription machinery generates the RNA primers needed
      for initiation of heavy strand DNA synthesis. Most DNA replication events from
      the heavy strand origin are prematurely terminated, forming a persistent RNA-DNA
      hybrid, which remains annealed to the parental DNA strand. This triple-stranded
      structure is called the D-loop and encompasses the conserved sequence box II, a
      DNA element required for proper primer formation. We here use a purified
      recombinant mitochondrial transcription system and demonstrate that conserved
      sequence box II is a sequence-dependent transcription termination element in
      vitro. Transcription from the light strand promoter is prematurely terminated at
      positions 300-282 in the mitochondrial genome, which coincide with the major RNA
      DNA transition points in the D-loop of human mitochondria. Based on our findings,
      we propose a model for primer formation at the origin of heavy strand DNA
      replication.

PMID- 16790427
TI  - Binding and transport of metal ions at the dimer interface of the Escherichia
      coli metal transporter YiiP.
AB  - YiiP is a representative member of the cation diffusion facilitator (CDF) family,
      a class of ubiquitous metal transporters that play an essential role in metal
      homeostasis. Recently, a pair of Zn2+/Cd2+-selective binding sites has been
      localized to two highly conserved aspartyl residues (Asp157), each in a 2-fold
      symmetry-related transmembrane segment 5 (TM5) of a YiiP homodimer. Here we
      report the functional and structural interactions between Asp157 and yet another
      highly conserved Asp49 in the TM2. Calorimetric binding analysis indicated that
      Asp49 and Asp157 contribute to a common Cd2+ binding site in each subunit. Copper
      phenanthroline oxidation of YiiP(D49C), YiiP(D157C), and YiiP(D49C/D157C) yielded
      inter- and intra-subunit cross-links among Cys49 and Cys157, consistent with the
      spatial proximity of two (Asp49-Asp157) sites at the dimer interface. Hg2+
      binding to YiiP(D49C) or YiiP(D49C/D157C) also yielded a Cys49-Hg2+-Cys49
      biscysteinate complex across the dimer interface, further establishing the
      interfacial location of a (Asp49-Asp157)2 bimetal binding center. Two bound Cd2+
      ions were found transported cooperatively with a sigmoidal dependence on the Cd2+
      concentration (n = 1.4). The binding affinity, transport cooperativity, and rate
      were modestly reduced by either a D49C or D157C mutation, but greatly diminished
      when all the bidentate aspartate O-ligands in (Asp49-Asp157)2 were replaced by
      the monodentate cysteine S-ligands. The functional significance of these findings
      is discussed based on the unique coordination chemistry of aspartyl residues and
      a model for the translocation pathway of metal ions at the YiiP dimer interface.

PMID- 16790428
TI  - Increased prolyl 4-hydroxylase domain proteins compensate for decreased oxygen
      levels. Evidence for an autoregulatory oxygen-sensing system.
AB  - Prolyl 4-hydroxylase domain (PHD) proteins are oxygen-dependent enzymes that
      hydroxylate hypoxia-inducible transcription factor (HIF) alpha-subunits, leading
      to their subsequent ubiquitination and degradation. Paradoxically, the expression
      of two family members (PHD2 and PHD3) is induced in hypoxic cell culture despite
      the reduced availability of the oxygen co-substrate, and it has been suggested
      that they become functionally relevant following re-oxygenation to rapidly
      terminate the HIF response. Here we show that PHDs are also induced in hypoxic
      mice in vivo, albeit in a tissue-specific manner. As demonstrated under
      chronically hypoxic conditions in vitro, PHD2 and PHD3 show a transient maximum
      but remain up-regulated over more than 10 days, suggesting a feedback down
      regulation of HIF-1alpha which then levels off at a novel set point. Indeed,
      hypoxic induction of PHD2 and PHD3 is paralleled by the attenuation of endogenous
      HIF-1alpha. Using an engineered oxygen-sensitive reporter gene in a cellular
      background lacking endogenous HIF-1alpha and hence inducible PHD expression, we
      could show that increased exogenous PHD levels can compensate for a wide range of
      hypoxic conditions. Similar data were obtained in a reconstituted cell-free
      system in vitro. In summary, these results suggest that due to their high O2 Km
      values, PHDs have optimal oxygen-sensing properties under all physiologically
      relevant oxygen concentrations; increased PHDs play a functional role even under
      oxygen-deprived conditions, allowing the HIF system to adapt to a novel oxygen
      threshold and to respond to another hypoxic insult. Furthermore, such an
      autoregulatory oxygen-sensing system would explain how a single mechanism works
      in a wide variety of differently oxygenated tissues.

PMID- 16790429
TI  - The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal
      epithelial cells.
AB  - Polycystin 1, the product of the PKD1 gene, is mutated in autosomal dominant
      polycystic kidney disease, a disease characterized by renal cyst formation and
      progressive renal failure. We show that expression of the C-terminal domain of
      human polycystin-1 (PKD1-CT) triggers spreading of isolated inner medullary
      collecting duct cells, a process mediated by Erk. As inner medullary collecting
      duct cells spread, PKD1-CT localizes to cell-extracellular matrix contacts,
      interacts with focal adhesion proteins Fak and paxillin, and stimulates Fak
      phosphorylation, paxillin phosphorylation, Fak-paxillin association, and
      formation of small focal complexes. PKD1-CT-mediated spreading requires membrane
      localization and the integrity of the C-terminal protein binding sites. We
      additionally show that Pkd1 null proximal tubule cells generated from Pkd1(flox/
      ):TSLargeT mice by in vitro Cre recombinase transfection demonstrate diminished
      spreading when compared with Pkd(flox/-) heterozygous parental cells. These
      findings suggest that membrane-bound PC1 has a central role in regulating
      morphogenic protein signaling at cell-matrix interfaces in non-confluent cells.

PMID- 16790430
TI  - AtIREG2 encodes a tonoplast transport protein involved in iron-dependent nickel
      detoxification in Arabidopsis thaliana roots.
AB  - Iron acquisition in Arabidopsis depends mainly on AtIRT1, a Fe2+ transporter in
      the plasma membrane of root cells. However, substrate specificity of AtIRT1 is
      low, leading to an excess accumulation of other transition metals in iron
      deficient plants. In the present study we describe AtIREG2 as a nickel
      transporter at the vacuolar membrane that counterbalances the low substrate
      specificity of AtIRT1 and possibly other iron transport systems in iron-deficient
      root cells. AtIREG2 is co-regulated with AtIRT1 by the transcription factor
      FRU/FIT1, encodes a membrane protein, which has 10 putative transmembrane domains
      and shares homology with vertebrate Fe2+ exporters. Heterologous expression of
      AtIREG2 in various yeast mutants, however, did not demonstrate an iron transport
      function. Instead, expression in wild-type and nickel-sensitive cot1 yeast cells
      conferred enhanced tolerance to elevated concentrations of nickel at acidic pH. A
      role in vacuolar substrate transport was further supported by localization of
      AtIREG2-GFP fusion proteins to the tonoplast in Arabidopsis suspension cells and
      root cells of intact plants. Transgenic plants overexpressing AtIREG2 showed an
      increased tolerance to elevated concentrations of nickel, whereas T-DNA insertion
      lines lacking AtIREG2 expression were more sensitive to nickel, particularly
      under iron deficiency, and accumulated less nickel in roots. We therefore propose
      a role of AtIREG2 in vacuolar loading of nickel under iron deficiency and thus
      identify it as a novel component in the iron deficiency stress response.

PMID- 16790431
TI  - Retrocyclins kill bacilli and germinating spores of Bacillus anthracis and
      inactivate anthrax lethal toxin.
AB  - Theta-defensins are cyclic octadecapeptides encoded by the modified alpha
      defensin genes of certain nonhuman primates. The recent demonstration that human
      alpha-defensins could prevent deleterious effects of anthrax lethal toxin in
      vitro and in vivo led us to examine the effects of theta-defensins on Bacillus
      anthracis (Sterne). We tested rhesus theta-defensins 1-3, retrocyclins 1-3, and
      several analogues of RC-1. Low concentrations of theta-defensins not only killed
      vegetative cells of B. anthracis (Sterne) and rendered their germinating spores
      nonviable, they also inactivated the enzymatic activity of anthrax lethal factor
      and protected murine RAW-264.7 cells from lethal toxin, a mixture of lethal
      factor and protective antigen. Structure-function studies indicated that the
      cyclic backbone, intramolecular tri-disulfide ladder, and arginine residues of
      theta-defensins contributed substantially to these protective effects. Surface
      plasmon resonance studies showed that retrocyclins bound the lethal factor
      rapidly and with high affinity. Retrocyclin-mediated inhibition of the enzymatic
      activity of lethal factor increased substantially if the enzyme and peptide were
      preincubated before substrate was added. The temporal discrepancy between the
      rapidity of binding and the slowly progressive extent of lethal factor inhibition
      suggest that post-binding events, perhaps in situ oligomerization, contribute to
      the antitoxic properties of retrocyclins. Overall, these findings suggest that
      theta-defensins provide molecular templates that could be used to create novel
      agents effective against B. anthracis and its toxins.

PMID- 16790432
TI  - Enzymatic properties of human aminopeptidase A. Regulation of its enzymatic
      activity by calcium and angiotensin IV.
AB  - Aminopeptidase A (APA) is a type II membrane-bound protein implicated in the
      regulation of blood pressure in the brain renin-angiotensin system. In this
      study, a recombinant soluble form of APA was expressed in a baculovirus system,
      purified to homogeneity, and characterized. By using synthetic substrates, it was
      shown that although the enzyme has a rather broad substrate specificity in the
      absence of Ca2+, the preferential release of acidic amino acid residues was
      observed in the presence of Ca2+. Moreover, Ca2+ up- or down-regulated the
      enzymatic activity depending on the substrate. By searching for natural
      substrates of APA, we found that peptides having acidic amino acids at their N
      terminus (angiotensin II, neurokinin B, cholecystokinin-8, and chromogranin A)
      were cleaved by the enzyme efficiently in the presence but not in the absence of
      Ca2+. Moreover kallidin (Lys-bradykinin) was converted to bradykinin effectively
      only in the absence of Ca2+. These results suggest that Ca2+ increases the
      preference of the enzyme for the peptide substrates having N-terminal acidic
      amino acids. In addition, we found that angiotensin IV could bind to APA both in
      the presence and absence of Ca2+ and inhibited the enzymatic activity of APA
      competitively, suggesting that angiotensin IV acts as a negative regulator of the
      enzyme once generated from angiotensin II by the serial actions of
      aminopeptidases. Taken together, these results suggest that there exists a
      complex regulation of the enzymatic activity of APA, which may contribute to
      homeostasis such as regulation of blood pressure, maintenance of memory, and
      normal pregnancy by controlling the concentrations of peptide substrates.

PMID- 16790433
TI  - Modulation of Stat3 activation by the cytosolic phospholipase A2alpha and
      cyclooxygenase-2-controlled prostaglandin E2 signaling pathway.
AB  - A variety of human cancers show constitutive activation of signal transducer and
      activator of transcription-3 (Stat3) and overexpression of cyclooxygenase-2 (COX
      2). This study describes a novel cross-talk between the COX-2-controlled
      prostaglandin E(2) (PGE(2)) and Stat3 signaling pathways that coordinately
      regulate human cancer cell growth. COX-2-derived PGE(2) induces interleukin-6
      production through activation of EP(4) receptor and subsequent phosphorylation of
      gp130/Stat3 in human cholangiocarcinoma cells. In parallel, activation of COX
      2/PGE(2) signaling also enhances Stat3 phosphorylation and reporter activity
      through EP(1) receptor-induced activation of c-Src and EGFR in these cells.
      Moreover, the observations that EP(1) receptor is detected in the nucleus as well
      as in the Stat3.DNA binding complex and that activation of EP(1) receptor in the
      nuclei enhances Stat3 activation depicts a previously undescribed G protein
      coupled receptor in the nucleus for Stat3 activation and tumor cell growth.

PMID- 16790434
TI  - Structural basis for D-amino acid transamination by the pyridoxal 5'-phosphate
      dependent catalytic antibody 15A9.
AB  - Antibody 15A9, raised with 5'-phosphopyridoxyl (PPL)-N(epsilon)-acetyl-L-lysine
      as hapten, catalyzes the reversible transamination of hydrophobic D-amino acids
      with pyridoxal 5'-phosphate (PLP). The crystal structures of the complexes of Fab
      15A9 with PPL-L-alanine, PPL-D-alanine, and the hapten were determined at 2.3,
      2.3, and 2.5A resolution, respectively, and served for modeling the complexes
      with the corresponding planar imine adducts. The conformation of the PLP-amino
      acid adduct and its interactions with 15A9 are similar to those occurring in PLP
      dependent enzymes, except that the amino acid substrate is only weakly bound,
      and, due to the immunization and selection strategy, the lysine residue that
      covalently binds PLP in these enzymes is missing. However, the N-acetyl-L-lysine
      moiety of the hapten appears to have selected for aromatic residues in
      hypervariable loop H3 (Trp-H100e and Tyr-H100b), which, together with Lys-H96,
      create an anion-binding environment in the active site. The structural situation
      and mutagenesis experiments indicate that two catalytic residues facilitate the
      transamination reaction of the PLP-D-alanine aldimine. The space vacated by the
      absent L-lysine side chain of the hapten can be filled, in both PLP-alanine
      aldimine complexes, by mobile Tyr-H100b. This group can stabilize a hydroxide
      ion, which, however, abstracts the C alpha proton only from D-alanine. Together
      with the absence of any residue capable of deprotonating C alpha of L-alanine,
      Tyr-H100b thus underlies the enantiomeric selectivity of 15A9. The reprotonation
      of C4' of PLP, the rate-limiting step of 15A9-catalyzed transamination, is most
      likely performed by a water molecule that, assisted by Lys-H96, produces a
      hydroxide ion stabilized by the anion-binding environment.

PMID- 16790435
TI  - Transcriptional regulation of uterine vascular endothelial growth factor during
      early gestation in a carnivore model, Mustela vison.
AB  - Vascular endothelial growth factor (VEGF) is an essential angiogenic signaling
      element that acts through its two tyrosine kinase receptors, inducing both
      proliferation of endothelial cells and vascular permeability. Given the
      importance of vasculogenesis and angiogenesis to early pregnancy, it is of
      interest to understand the mechanisms regulating vascular development at this
      stage. We previously demonstrated that VEGF and receptors are up-regulated during
      embryo implantation in an unique animal model, the mink, a species displaying
      obligate embryonic diapause. Herein we examined the role of prostaglandin E2
      (PGE(2)) as a regulator of VEGF during early pregnancy and established the
      mechanisms of this regulation. We demonstrate that activated embryos secrete
      PGE(2) and that expression of PGE synthase protein in the uterus is dependent
      upon direct contact with invading trophoblast cells during implantation. Using
      mink uterine stromal cells transfected with mink VEGF promoter driving the
      luciferase reporter gene, we show that PGE(2) induces promoter transactivation
      and that this response can be eliminated by blockade of protein kinase A.
      Treatment with antagonists to PGE(2) receptors EP2 and EP4 eliminated the PGE(2)
      induced response in transfected cells. Deletional studies of the promoter
      revealed that a region of 99 bp upstream of the transcription start site is
      required for PGE(2)-induced transactivation. Mutation of an AP2/Sp1 cluster,
      found within the 99 bp, completely eliminated the PGE(2) response. Furthermore,
      chromatin immunoprecipitation assays confirmed binding of the AP2 and Sp1
      transcription factors to the endogenous mink VEGF promoter in uterine cells.
      PGE(2) stimulated acetylation of histone H3 associated with the promoter region
      containing the AP2/Sp1 cluster. Taken together, these results demonstrate that
      PGE(2) plays an important role in regulating uterine and thus placental vascular
      development, acting through its receptors EP2 and EP4, provoking protein kinase A
      activation of AP2 and Sp1 as well as acetylation of histone H3 to transactivate
      the VEGF promoter.

PMID- 16790436
TI  - Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation
      of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2
      Keap1 complex.
AB  - The prevalence and mechanistic significance of self-association among substrate
      adaptors for the Cul-Rbx family of ubiquitin ligases remain unclear. We now
      report that it is as a homodimer that the substrate adaptor Keap1 interacts with
      Cul3. The resulting complex facilitates ubiquitylation of the Nrf2 transcription
      factor but only when this substrate possesses within its Neh2 domain a second
      cryptic Keap1-binding site, the DLG motif, in addition to its previously
      described ETGE site. Both motifs recognize overlapping surfaces on Keap1, and the
      seven lysine residues of Nrf2 that act as ubiquitin acceptors lie between them.
      Based on these data, we propose a "fixed-ends" model for Nrf2 ubiquitylation in
      which each binding site becomes tethered to a separate subunit of the Keap1
      homodimer. This two-site interaction between Keap1 and Nrf2 constrains the
      mobility of the target lysine residues in the Neh2 domain, increasing their
      average concentration in the vicinity of the Rbx-bound ubiquitin-conjugating
      enzyme, and thus the rate at which the transcription factor is ubiquitylated. We
      show that self-association is a general feature of Cul3 substrate adaptors and
      propose that the fixed-ends mechanism is commonly utilized to recruit, orientate,
      and ubiquitylate substrates upon this family of ubiquitin ligases.

PMID- 16790437
TI  - The proprotein convertase SKI-1/S1P. In vitro analysis of Lassa virus
      glycoprotein-derived substrates and ex vivo validation of irreversible peptide
      inhibitors.
AB  - Herein we designed, synthesized, tested, and validated fluorogenic
      methylcoumarinamide (MCA) and chloromethylketone-peptides spanning the Lassa
      virus GPC cleavage site as substrates and inhibitors for the proprotein
      convertase SKI-1/S1P. The 7-mer MCA (YISRRLL-MCA) and 8-mer MCA (IYISRRLL-MCA)
      are very efficiently cleaved with respect to both the 6-mer MCA (ISRRLL-MCA) and
      point mutated fluorogenic analogues, except for the 7-mer mutant Y253F. The
      importance of the P7 phenylic residue was confirmed by digestions of two 16-mer
      non-fluorogenic peptidyl substrates that differ by a single point mutation
      (Y253A). Because NMR analysis of these 16-mer peptides did not reveal significant
      structural differences at recognition motif RRLL, the P7 Tyr residue is likely
      important in establishing key interactions within the catalytic pocket of SKI-1.
      Based on these data, we established through analysis of pro-ATF6 and pro-SREBP-2
      cellular processing that decanoylated chloromethylketone 7-mer, 6-mer, and 4-mer
      peptides containing the core RRLL sequence are irreversible and potent ex vivo
      SKI-1 inhibitors. Although caution must be exercised in using these inhibitors in
      in vitro reactions, as they can also inhibit the basic amino acid-specific
      convertase furin, within cells and when used at concentrations < or = 100 microM
      these inhibitors are relatively specific for inhibition of SKI-1 processing
      events, as opposed to those performed by furin-like convertases.

PMID- 16790438
TI  - Androcam is a tissue-specific light chain for myosin VI in the Drosophila testis.
AB  - Myosin VI, a ubiquitously expressed unconventional myosin, has roles in a broad
      array of biological processes. Unusual for this motor family, myosin VI moves
      toward the minus (pointed) end of actin filaments. Myosin VI has two light chain
      binding sites that can both bind calmodulin (CaM). However unconventional myosins
      could use tissue-specific light chains to modify their activity. In the
      Drosophila testis, myosin VI is important for maintenance of moving actin
      structures, called actin cones, which mediate spermatid individualization. A CaM
      related protein, Androcam (Acam), is abundantly expressed in the testis and like
      myosin VI, accumulates on these cones. We have investigated the possibility that
      Acam is a testis-specific light chain of Drosophila myosin VI. We find that Acam
      and myosin VI precisely colocalize at the leading edge of the actin cones and
      that myosin VI is necessary for this Acam localization. Further, myosin VI and
      Acam co-immunoprecipitate from the testis and interact in yeast two-hybrid
      assays. Finally Acam binds with high affinity to peptide versions of both myosin
      VI light chain binding sites. In contrast, although Drosophila CaM also shows
      high affinity interactions with these peptides, we cannot detect a CaM/myosin VI
      interaction in the testis. We conclude that Acam and not CaM acts as a myosin VI
      light chain in the Drosophila testis and hypothesize that it may alter the
      regulation of myosin VI in this tissue.

PMID- 16790439
TI  - Dimerization of the scaffolding protein ZO-1 through the second PDZ domain.
AB  - The tight junction protein ZO-1 is known to link the transmembrane proteins
      occludin, claudins, and JAMs to many cytoplasmic proteins and the actin
      cytoskeleton. Although specific roles for ZO-1 at the tight junction are unknown,
      it is widely assumed that ZO-1, together with its homologs ZO-2 and ZO-3, serves
      as a platform to scaffold various transmembrane and cytoplasmic tight junction
      proteins. Thus the manner in which the zonula occludens (ZO) proteins multimerize
      has implications for the protein networks they can coordinate. The purpose of our
      study was to determine whether ZO-1 forms homodimers and to determine the protein
      interaction region. Using laser light scattering and analytical centrifugation,
      we show that protein sequences corresponding to the NH(2)-terminal half of ZO-1
      form stable homodimers with a submicromolar equilibrium dissociation constant.
      Analysis of the molecular weight of different truncated forms of ZO-1 revealed
      that the second PDZ domain is both necessary and sufficient for dimerization.
      This interaction does not use the beta-finger motif described for other PDZ
      dimers. Furthermore, ZO-1 does not dimerize via an Src homology 3 to Guk domain
      interaction as was demonstrated previously for MAGUKs, like PSD-95. Results from
      immunoprecipitation experiments with polarized Madin-Darby canine kidney
      epithelial cells stably transfected with full-length GFP-ZO-1 indicate that a
      substantial portion of ZO-1 forms homodimers in vivo. As described previously, ZO
      1 also forms heterodimers with ZO-2 and ZO-3. We conclude that the dimerization
      of ZO proteins is unlike that of other MAGUKs and that the previously
      unrecognized ZO-1 homodimers may allow formation of protein networks distinct
      from those of heterodimers with ZO-2 and ZO-3.

PMID- 16790440
TI  - Structure-function relationships in the neuropeptide S receptor: molecular
      consequences of the asthma-associated mutation N107I.
AB  - Neuropeptide S (NPS) and its receptor (NPSR) are thought to have a role in asthma
      pathogenesis; a number of single nucleotide polymorphisms within NPSR have been
      shown to be associated with an increased prevalance of asthma. One such single
      nucleotide polymorphism leads to the missense mutation N107I, which results in an
      increase in the potency of NPS for NPSR. To gain insight into structure-function
      relationships within NPS and NPSR, we first carried out a limited structural
      characterization of NPS and subjected the peptide to extensive mutagenesis
      studies. Our results show that the NH(2)-terminal third of NPS, in particular
      residues Phe-2, Arg-3, Asn-4, and Val-6, are necessary and sufficient for
      activation of NPSR. Furthermore, part of a nascent helix within the peptide,
      spanning residues 5 through 13, acts as a regulatory region that inhibits
      receptor activation. Notably, this inhibition is absent in the asthma-linked
      N107I variant of NPSR, suggesting that residue 107 interacts with the
      aforementioned regulatory region of NPS. Whereas this interaction may be at the
      root of the increase in potency associated with the N107I variant, we show here
      that the mutation also causes an increase in cell-surface expression of the
      mutant receptor, leading to a concomitant increase in the maximal efficacy
      (E(max)) of NPS. Our results identify the key residues of NPS involved in NPSR
      activation and suggest a molecular basis for the functional effects of the N107I
      mutation and for its putative pathophysiological link with asthma.

PMID- 16790441
TI  - Crystal structures of chloroperoxidase with its bound substrates and complexed
      with formate, acetate, and nitrate.
AB  - Chloroperoxidase (CPO) is a heme-thiolate enzyme that catalyzes hydrogen peroxide
      dependent halogenation reactions. Structural data on substrate binding have not
      been available so far. CPO was therefore crystallized in the presence of iodide
      or bromide. One halide binding site was identified at the surface near a narrow
      channel that connects the surface with the heme. Two other halide binding sites
      were identified within and at the other end of this channel. Together, these
      sites suggest a pathway for access of halide anions to the active site. The
      structure of CPO complexed with its natural substrate cyclopentanedione was
      determined at a resolution of 1.8 A. This is the first example of a CPO structure
      with a bound organic substrate. In addition, structures of CPO bound with
      nitrate, acetate, and formate and of a ternary complex with dimethylsulfoxide
      (Me2SO) and cyanide were determined. These structures have implications for the
      mechanism of compound I formation. Before binding to the heme, the incoming
      hydrogen peroxide first interacts with Glu-183. The deprotonated Glu-183
      abstracts a proton from hydrogen peroxide. The hydroperoxo-anion then binds at
      the heme, yielding compound 0. Glu-183 protonates the distal oxygen of compound
      0, water is released, and compound I is formed.

PMID- 16790442
TI  - Characterization of mechanisms involved in secretion of active heparanase.
AB  - Heparanase is an endo-beta-D-glucuronidase involved in extracellular matrix
      remodeling and degradation and implicated in tumor metastasis, angiogenesis,
      inflammation, and autoimmunity. The enzyme is synthesized as a latent 65-kDa
      protein and is processed in the lysosomal compartment to an active 58-kDa
      heterodimer, where it is stored in a stable form. In contrast, its heparan
      sulfate substrate is localized extracellularly, suggesting the existence of
      mechanisms that trigger heparanase secretion. Here we show that secretion of the
      active enzyme is mediated by the protein kinase A and C pathways. Moreover,
      secretion of active heparanase was observed upon cell stimulation with
      physiological concentrations of adenosine, ADP, and ATP, as well as by the
      noncleavable ATP analogue adenosine 5'-O-(thiotriphosphate). Indeed, heparanase
      secretion was noted upon cell stimulation with a specific P2Y1 receptor agonist
      and was inhibited by P2Y receptor antagonists. The kinetics of heparanase
      secretion resembled the secretion of cathepsin D, a lysosomal enzyme, indicating
      that the secreted heparanase is of lysosomal origin. We suggest that secretion of
      active heparanase is initiated by extracellular cues activating the protein
      kinase A and C signaling pathways. The secreted enzyme(s) then facilitate cell
      invasion associated with cancer metastasis, angiogenesis, and inflammation.

PMID- 16790444
TI  - Glutamate inhibits chondral mineralization through apoptotic cell death mediated
      by retrograde operation of the cystine/glutamate antiporter.
AB  - Although we have previously demonstrated the functional significance of
      excitatory amino acid transporters as well as glutamate (Glu) receptors (GluRs)
      expressed by chondrocytes, little attention has been paid to the possible
      expression of the cystine/Glu antiporter responsible for the bi-directional
      transmembrane transport of Glu in chondrocytes to date. In organotypic cultured
      mouse embryonic metatarsals isolated before vascularization, the chondral
      mineralization was significantly decreased in the presence of Glu at a high
      concentration. Apoptotic cells were detected within the late proliferating and
      prehypertrophic chondrocytic layers in metatarsals cultured in the presence of
      Glu. A group III metabotropic GluR (mGluR) antagonist partially, but
      significantly, prevented the inhibition of mineralization by Glu in metatarsals
      without affecting the number of apoptotic cells. Both decreased mineralization
      and apoptosis by Glu were significantly prevented by the addition of the
      cystine/Glu antiporter inhibitor homocysteic acid, as well as reduced glutathione
      (GSH) and cystine. Expression of mRNA for xCT and 4F2hc subunits, which are
      components of the cystine/Glu antiporter, was seen in both cultured mouse
      metatarsals and rat costal chondrocytes. In chondrocytes cultured with Glu, a
      significant decrease was seen in intracellular GSH levels, together with
      increases in the number of apoptotic cells and the level of intracellular
      reactive oxygen species. These results suggest that Glu could regulate
      chondrogenic differentiation toward mineralization through a mechanism associated
      with apoptosis mediated by the depletion of intracellular GSH after the
      retrograde operation of the cystine/Glu antiporter, in addition to the activation
      of group III mGluR, in chondrocytes.

PMID- 16790445
TI  - Analysis of the complex between Ca2+ channel beta-subunit and the Rem GTPase.
AB  - Voltage-gated calcium channels are multiprotein complexes that regulate calcium
      influx and are important contributors to cardiac excitability and contractility.
      The auxiliary beta-subunit (CaV beta) binds a conserved domain (the alpha
      interaction domain (AID)) of the pore-forming CaV alpha1 subunit to modulate
      channel gating properties and promote cell surface trafficking. Recently, members
      of the RGK family of small GTPases (Rem, Rem2, Rad, Gem/Kir) have been identified
      as novel contributors to the regulation of L-type calcium channel activity. Here,
      we describe the Rem-association domain within CaV beta2a. The Rem interaction
      module is located in a approximately 130-residue region within the highly
      conserved guanylate kinase domain that also directs AID binding. Importantly, CaV
      beta mutants were identified that lost the ability to bind AID but retained their
      association with Rem, indicating that the AID and Rem association sites of CaV
      beta2a are structurally distinct. In vitro binding studies indicate that the
      affinity of Rem for CaV beta2a interaction is lower than that of AID for CaV
      beta2a. Furthermore, in vitro binding studies indicate that Rem association does
      not inhibit the interaction of CaV beta2a with AID. Instead, CaV beta can
      simultaneously associate with both Rem and CaV alpha1-AID. Previous studies had
      suggested that RGK proteins may regulate Ca2+ channel activity by blocking the
      association of CaV beta subunits with CaV alpha1 to inhibit plasma membrane
      trafficking. However, surface biotinylation studies in HIT-T15 cells indicate
      that Rem can acutely modulate channel function without decreasing the density of
      L-type channels at the plasma membrane. Together these data suggest that Rem
      dependent Ca2+ channel modulation involves formation of a Rem x CaV beta x AID
      regulatory complex without the need to disrupt CaV alpha1 x CaV beta association
      or alter CaV alpha1 expression at the plasma membrane.

PMID- 16790443
TI  - The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not
      for the anabolic bone response to parathyroid hormone treatment.
AB  - The cell surface receptor, low-density lipoprotein receptor-related protein 5
      (LRP5) is a key regulator of bone mass. Loss-of-function mutations in LRP5 cause
      the human skeletal disease osteoporosis-pseudoglioma syndrome, an autosomal
      recessive disorder characterized by severely reduced bone mass and strength. We
      investigated the role of LRP5 on bone strength using mice engineered with a loss
      of-function mutation in the gene. We then tested whether the osteogenic response
      to mechanical loading was affected by the loss of Lrp5 signaling. Lrp5-null (Lrp5
      /-) mice exhibited significantly lower bone mineral density and decreased
      strength. The osteogenic response to mechanical loading of the ulna was reduced
      by 88 to 99% in Lrp5-/- mice, yet osteoblast recruitment and/or activation at
      mechanically strained surfaces was normal. Subsequent experiments demonstrated an
      inability of Lrp5-/- osteoblasts to synthesize the bone matrix protein
      osteopontin after a mechanical stimulus. We then tested whether Lrp5-/- mice
      increased bone formation in response to intermittent parathyroid hormone (PTH), a
      known anabolic treatment. A 4-week course of intermittent PTH (40 microg/kg/day;
      5 days/week) enhanced skeletal mass equally in Lrp5-/- and Lrp5+/+ mice,
      suggesting that the anabolic effects of PTH do not require Lrp5 signaling. We
      conclude that Lrp5 is critical for mechanotransduction in osteoblasts. Lrp5 is a
      mediator of mature osteoblast function following loading. Our data suggest an
      important component of the skeletal fragility phenotype in individuals affected
      with osteoporosis-pseudoglioma is inadequate processing of signals derived from
      mechanical stimulation and that PTH might be an effective treatment for improving
      bone mass in these patients.

PMID- 16790446
TI  - A specific isoform of nonmuscle myosin II-C is required for cytokinesis in a
      tumor cell line.
AB  - Nonmuscle myosin IIs play an essential role during cytokinesis. Here, we explore
      the function of an alternatively spliced isoform of nonmuscle myosin heavy chain
      (NMHC) II-C, called NMHC II-C1, in the A549 human lung tumor cell line during
      cytokinesis. NMHC II-C1 contains an insert of 8 amino acids in the head region of
      NMHC II-C. First, we show that there is a marked increase in both the mRNA
      encoding NMHC II-C1 and protein in tumor cell lines compared with nontumor cell
      lines derived from the same tissue. Quantification of the amount of myosin II
      isoforms in the A549 cells shows that the amounts of NMHC II-A and II-C1 protein
      are about equal and substantially greater than NMHC II-B. Using specific siRNAs
      to decrease NMHC II-C1 in cultured A549 cells resulted in a 5.5-fold decrease in
      the number of cells at 120 h, whereas decreasing NMHC II-A with siRNA does not
      affect cell proliferation. This decreased proliferation can be rescued by
      reintroducing NMHC II-C1 but not NMHC II-A or II-B into A549 cells, although
      noninserted NMHC II-C does rescue to a limited extent. Time lapse video
      microscopy revealed that loss of NMHC II-C1 leads to a delay in cytokinesis and
      prolongs it from 2 to 8-10 h. These findings are consistent with the localization
      of NMHC II-C1 to the intercellular bridge that attaches the two dividing cells
      during the late phases of cytokinesis. The results suggest a specific function
      for NMHC II-C1 in cytokinesis in the A549 tumor cell line.

PMID- 16790449
TI  - Intraoperative examination of sentinel lymph nodes by ultrarapid
      immunohistochemistry in breast cancer.
AB  - BACKGROUND: The ultrarapid immunohistochemistry (IHC) technique was applied to
      the intraoperative examination of sentinel lymph nodes (SLNs) because routine SLN
      frozen section examinations sometimes produce false-negative results. The present
      study was undertaken to develop a reliable protocol for the ultrarapid IHC of
      SLNs. METHODS: SLNs from 79 breast cancer patients with clinically negative
      axillary node were examined intraoperatively by frozen hematoxylin-eosin (H&E)
      stain and by ultrarapid cytokeratin IHC assay. On the basis of the result of
      serially sectioned permanent study, the sensitivity and accuracy of each
      intraoperative technique were compared. RESULTS: The total number of dissected
      SLNs was 178 with a mean of 2.3 (1-5) per patient. The mean turnaround time for
      ultrarapid IHC was 20 min. The sensitivity rates of frozen H&E staining and
      ultrarapid IHC were 70.0 and 85.0%, respectively (P = 0.083). Each method had a
      specificity of 100%. The accuracy rates for frozen H&E staining and rapid IHC
      were 92.4 and 96.2%, respectively (P = 0.083). Ultrarapid IHC detected one
      additional patient with sentinel node micrometastasis and two additional patients
      with isolated tumor cells (ITCs). In those patients, two underwent completion
      axillary dissection simultaneously and could avoid a second operation.
      CONCLUSIONS: Ultrarapid cytokeratin IHC enhanced the intraoperative detection of
      sentinel node micrometastasis and ITCs in breast cancer without consuming much
      time. In patients who need completion axillary dissection after sentinel node
      biopsy, this technique could be helpful in avoiding a second operation.

PMID- 16790450
TI  - Completion and toxicity of induction chemotherapy for metastatic testicular
      cancer: an updated evaluation of Japanese patients.
AB  - BACKGROUND: Combination of bleomycin, etoposide and cisplatin (BEP) remains the
      standard chemotherapy for testicular cancer. Since the development of BEP in the
      1980s, there has been a considerable advance in supportive therapies, such as
      granulocyte colony-stimulating-factor and 5-HT3 antagonists. Therefore, we re
      evaluated the completion and toxicity of BEP combined with modern supportive
      care. METHODS: The medical records of all 42 testicular cancer patients who
      received induction chemotherapy at Tsukuba University Hospital were reviewed.
      Toxicities during the induction chemotherapy were graded according to the
      Japanese CTCAE v3.0. RESULTS: Dose reduction was needed in only three patients.
      The subsequent chemotherapy was started at the planned 3 week interval or within
      3 days of postponement in 89% of the treatment cycles. The average relative dose
      intensity (RDI) of bleomycin was 0.95, while that for etoposide and cisplatin was
      0.97. There was no death due to toxicity. The most frequent toxicity was
      leukopenia (grade 3 in 44% and grade 4 in 55%). Post-chemotherapy diffusion
      capacity was significantly decreased in 30% of patients. Two patients developed
      bleomycin-induced pneumonitis, but recovered successfully. Sixteen patients
      received second line or salvage chemotherapy after BEP, subsequently. The overall
      5 year cause-specific survival rate was 85%. CONCLUSION: BEP with high RDIs is
      acceptable if combined with modern supportive care, with acceptable toxicity
      profile in most patients.

PMID- 16790451
TI  - The impact of a coordinated transitional care programme on adolescents with
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: There is an extensive evidence base for the need of transitional care,
      but a paucity of robust outcome data. The aim of the study was to determine
      whether the quality of life of adolescents with juvenile idiopathic arthritis
      (JIA) could be improved by a co-ordinated, evidence-based programme of
      transitional care. METHODS: Adolescents with JIA aged 11, 14 and 17 yrs and their
      parents were recruited from 10 rheumatology centres in the UK. Data were
      collected at baseline, 6 and 12 months including core outcome variables. The
      primary outcome measure was health-related quality of life (HRQL): Juvenile
      Arthritis Quality of Life Questionnaire (JAQQ). Secondary outcome measures
      included: knowledge, satisfaction, independent health behaviours and pre
      vocational experience. RESULTS: Of the 359 families invited to participate, 308
      (86%) adolescents and 303 (84%) parents accepted. A fifth of them had persistent
      oligoarthritis. Median disease duration was 5.7 (0-16) yrs. Compared with
      baseline values, significant improvements in JAQQ scores were reported for
      adolescent and parent ratings at 6 and 12 months and for most secondary outcome
      measures with no significant deteriorations between 6 and 12 months. Continuous
      improvement was observed for both adolescent and parent knowledge with
      significantly greater improvement in the younger age groups at 12 months (P =
      0.002). CONCLUSIONS: This study represents the first objective evaluation of an
      evidence-based transitional care programme and demonstrates that such care can
      potentially improve adolescents' HRQL.

PMID- 16790452
TI  - Population screening for Chlamydia trachomatis infection in the UK: a qualitative
      study of the experiences of those screened.
AB  - BACKGROUND: Screening for Chlamydia trachomatis in selected health care settings
      is underway in the UK despite insufficient evidence about the personal impact of
      screening. OBJECTIVES: To describe men and women's experiences of being screened
      for chlamydia as part of the Chlamydia Screening Studies (ClaSS) project, a
      population-based UK study of postal screening for chlamydia. METHODS: We
      conducted in-depth interviews with 45 purposively sampled participants in the
      ClaSS project using a checklist of topics relating to their experiences of the
      screening process. Interviews were audio-tape recorded, transcribed verbatim and
      analysed using the constant comparison method. RESULTS: Four main themes emerged:
      initial discomfort with screening arising from an unease with sexual health
      issues; anxiety, especially after receiving a positive test result, due to the
      fear of informing sexual partners, the risk of infertility and the possibility of
      having other undetected infections; women's concern about being stigmatised for
      having been infected with chlamydia, which affected how they felt about
      themselves and how they thought others would perceive them; and recognising the
      need to balance the harms of screening with the benefits. Despite some reported
      adverse effects, no one regretted their decision to be screened. CONCLUSIONS:
      Public education and discussion of sexually transmitted infections should help to
      increase the acceptability of chlamydia screening and destigmatise a diagnosis of
      chlamydia. Those working in primary care settings are likely to become
      increasingly involved in chlamydia screening and so must be suitably trained to
      inform individuals of the potential adverse effects and to deal with their
      consequences.

PMID- 16790453
TI  - Upper abdominal ultrasound in general practice: indications, diagnostic yield and
      consequences for patient management.
AB  - BACKGROUND: Abdominal ultrasound (US) is frequently performed in Western
      societies. There is insufficient knowledge of its diagnostic value in terms of
      changes in patient management decisions in primary care. OBJECTIVE: To assess the
      influence of upper abdominal US on patient management in general practice.
      METHODS: A prospective cohort study with 76 GPs and three general hospitals in
      The Netherlands. A total of 395 patients aged >or=18 years referred by their GPs
      for upper abdominal US were included. The main outcome was change in anticipated
      patient management assessed by means of questionnaires filled in by GPs before
      and after abdominal US. RESULTS: Mean age of the patients was 54.0 +/- 15.8
      years, 35% were male. Clinically relevant abnormalities were found in 29% of the
      abdominal US, mainly cholelithiasis. Anticipated patient management changed in
      64% of the patients following abdominal US. Main changes included fewer referrals
      to a medical specialist (from 45 to 30%); and more frequent reassurance of the
      patient (from 15 to 43%). However, this reassurance was not perceived as such in
      almost 40% of these patients. A change in anticipated patient management occurred
      significantly more frequently in patients with a prior cholecystectomy (82%).
      CONCLUSION: Anticipated patient management by the GP changed in 64% of patients
      following upper abdominal US. Abdominal US substantially reduced the number of
      intended referrals to a medical specialist, and more patients could be reassured
      by their GP.

PMID- 16790454
TI  - Outpatient care utilization in urban Kerala, India.
AB  - CONTEXT: Kerala is characterized by a high density of public and private health
      infrastructure. While less inequality in access has been reported in this Indian
      state, few studies have looked at problems found within cities. Escalation of
      costs of private services and reduced public investments could generate some
      inequalities in access for the poor. OBJECTIVE: To assess factors associated with
      utilization and source of outpatient care in urban Kerala, and to discuss policy
      implications with regards to access to care. METHODS: A multilevel analysis of
      individual and urban characteristics associated with utilization and source of
      outpatient care was conducted using data from a 1995-96 survey by the National
      Sample Survey Organisation on health care in urban Kerala. RESULTS: There is a
      high level of utilization (83.6%) of allopathic medical services. Controlling for
      illness severity and age, utilization thereof was lower for the very poor (OR
      0.13 [0.03; 0.49]), inhabitants of medium towns (OR 0.20 [0.05; 0.70]), and
      inhabitants of cities with a lower proportion of permanent material (pucca)
      houses (0.21 [0.06; 0.72]). Among all users, 77% resorted to a private source of
      care. Utilization of a private provider was less likely for the very poor (OR
      0.13 [0.03; 0.51]) and individuals from casual worker households (OR 0.54 [0.30;
      0.97]), while it was more likely for inhabitants of cities from both low public
      bed density districts (OR 4.08 [1.05; 15.95]) and high private bed density
      districts (OR 5.83 [2.34; 14.53]). Problems of quality and accessibility of the
      public sector were invoked to justify utilization of private clinics. A marked
      heterogeneity in utilization of outpatient care was found between cities of
      various sizes and characteristics. CONCLUSION: This study confirms high
      utilization of private outpatient care in Kerala and suggests problems of access
      for the poorest. Even in a context of high public availability and considering
      the health transition factor, relying on the development of the private sector to
      respond to increasing health care needs could create inequalities in access.
      Investing in the public urban primary care system and ensuring access to quality
      health care for the poorest is warranted.

PMID- 16790455
TI  - Do group practices have lower caesarean rates than solo practice obstetric
      clinics? Evidence from Taiwan.
AB  - OBJECTIVE: This study examined physicians' propensity for caesarean deliveries at
      solo versus group practice obstetrics/gynaecology (ob/gyn) clinics in Taiwan.
      METHOD: We used population-based (National Health Insurance) claims data covering
      all 253 618 singleton deliveries conducted at ob/gyn clinics, during 2000-02. The
      dependent variable, delivery mode, was treated as dichotomous [caesarean section
      (CS) = 1, vaginal delivery (VD) = 0]. The independent variable of interest was
      practice size, classified into four categories: 1, 2, 3 and 4+ physicians.
      Multilevel logistic regression modelling, accounting for clinic-level variation
      in CS rates, was used to examine CS likelihood by practice size, among the total
      delivery sample and among the sub-samples disaggregated by obstetric complication
      status. RESULTS: Solo practices have 7% excess caesarean cases relative to large
      group practices. After controlling for patient's age, physician demographics, the
      clinic's geographic location and size of delivery service, and clinic-level
      random effect, solo practice physicians were 5.38 times as likely as 4+ physician
      practices to provide caesarean delivery (CI = 4.18 approximately 6.93), 2
      physician practices were 3.87 times (CI = 2.99 approximately 5.01) and 3
      physician practices 2.72 times (CI = 2.06 approximately 3.59) as likely as 4+
      physician practices to provide caesarean delivery. This effect is driven by
      higher CS propensity among solo and small groups among cases with obstetrically
      less salient complications and the 'no complications' subset of patients. Wide
      confidence intervals for odds ratios in these sub-samples also attest to wide
      variations in clinic-level CS rates among these patient groups. CONCLUSIONS: Solo
      physicians are the most likely to provide caesarean delivery, and CS likelihood
      decreases with increasing number of physicians in the practice. Group practice
      support may reduce the CS likelihood, when it is not clinically indicated. Policy
      makers should consider initiatives to limit full service delivery privileges to
      group practice obstetric clinics, in order to reduce unnecessary CS. Solo
      practice clinics should, at best, be licensed as birthing centres, required to
      transfer patients needing CS to a larger facility.

PMID- 16790456
TI  - Having the rug pulled from under your feet: one project's experience of the US
      policy reversal on sex work.
AB  - After the election of President George W Bush in 2000, US government policy
      toward sexual and reproductive health changed dramatically. In May 2003, the
      Global AIDS Act was passed and prohibits allocation of US government funds to
      organizations that 'promote or advocate' legalization and practice of
      prostitution and sex trafficking. There are few documented examples of early
      impacts of this policy reversal on USAID-funded programmes already working with
      sex worker communities. This paper offers an anecdotal account of one programme
      in Cambodia that found itself caught in the ideological cross-fire of US
      politics, and describes consequent negative effects on the project's ability to
      offer appropriate and effective HIV prevention services to vulnerable migrant sex
      workers.

PMID- 16790458
TI  - A meta-analysis of the association between adherence to drug therapy and
      mortality.
AB  - OBJECTIVE: To evaluate the relation between adherence to drug therapy, including
      placebo, and mortality. DESIGN: Meta-analysis of observational studies. DATA
      SOURCES: Electronic databases, contact with investigators, and textbooks and
      reviews on adherence. Review methods Predefined criteria were used to select
      studies reporting mortality among participants with good and poor adherence to
      drug therapy. Data were extracted for disease, drug therapy groups, methods for
      measurement of adherence rate, definition for good adherence, and mortality.
      RESULTS: Data were available from 21 studies (46,847 participants), including
      eight studies with placebo arms (19,633 participants). Compared with poor
      adherence, good adherence was associated with lower mortality (odds ratio 0.56,
      95% confidence interval 0.50 to 0.63). Good adherence to placebo was associated
      with lower mortality (0.56, 0.43 to 0.74), as was good adherence to beneficial
      drug therapy (0.55, 0.49 to 0.62). Good adherence to harmful drug therapy was
      associated with increased mortality (2.90, 1.04 to 8.11). CONCLUSION: Good
      adherence to drug therapy is associated with positive health outcomes. Moreover,
      the observed association between good adherence to placebo and mortality supports
      the existence of the "healthy adherer" effect, whereby adherence to drug therapy
      may be a surrogate marker for overall healthy behaviour.

PMID- 16790459
TI  - Risk in primary care of colorectal cancer from new onset rectal bleeding: 10 year
      prospective study.
AB  - OBJECTIVE: To measure the risk of colorectal cancer and adenoma with new onset
      rectal bleeding reported to primary care. DESIGN: Cohort study. SETTING: A rural
      general practice in the United Kingdom. PARTICIPANTS: Patients aged 45 or more
      with new onset rectal bleeding, irrespective of other symptoms. MAIN OUTCOME
      MEASURES: Percentage of participants in whom colorectal cancer or colonic adenoma
      was identified after investigation of the bowel. RESULTS: During a 10 year
      period, 265 patients reported new rectal bleeding. Of these, 15 (5.7%, 95%
      confidence interval 3.2% to 9.2%) had colorectal cancer, and 13 (4.9%, 2.6% to
      8.4%) had colonic adenoma. Only two of the patients with cancer had had
      diarrhoea. CONCLUSIONS: One in 10 patients aged 45 or more with new onset rectal
      bleeding had colonic neoplasia, so investigation of the bowel should be offered
      to all such patients, whether or not they have other symptoms.

PMID- 16790460
TI  - Effect on weight gain of routinely giving albendazole to preschool children
      during child health days in Uganda: cluster randomised controlled trial.
AB  - OBJECTIVE: To estimate the effectiveness of delivering an anthelmintic through a
      community child health programme on the weight gain of preschool children in
      Uganda. DESIGN: Cluster randomised controlled trial. SETTING: Eastern Uganda.
      PARTICIPANTS: 48 parishes participating in a new programme for child health: 24
      offered children an additional service of anthelmintic treatment. The outcome is
      based on measurements from 27,995 children. INTERVENTION: Treatment of children
      aged between 1 and 7 years with 400 mg albendazole added to standard services
      offered during child health days over a three year period. MAIN OUTCOME MEASURE:
      Weight gain. RESULTS: The provision of periodic anthelmintic treatment as a part
      of child health services in Uganda resulted in an increase in weight gain of
      about 10% (166 g per child per year, 95% confidence interval 16 to 316) above
      expected weight gain when treatments were given twice a year, and an increase of
      5% when the treatment was given annually. CONCLUSION: Deworming of preschool
      children in Uganda as part of regularly scheduled health services seems practical
      and associated with increased weight gain.

PMID- 16790461
TI  - Probiotics for prevention of recurrent vulvovaginal candidiasis: a review.
AB  - Vulvovaginal candidiasis (VVC) is a common infection affecting the quality of
      life of many women. Probiotics have been investigated as possible agents for the
      prevention of recurrences of VVC. We reviewed the available literature. In some
      studies the development of VVC was associated with either a low number of
      lactobacilli in the vagina or with the presence of H2O2-non-producing vaginal
      lactobacilli, although there are a few studies not supporting these statements.
      In addition, in vitro studies have shown that lactobacilli can inhibit the growth
      of Candida albicans and/or its adherence on the vaginal epithelium. The results
      of some clinical trials support the effectiveness of lactobacilli, especially
      Lactobacillus acidophilus, Lactobacillus rhamnosus GR-1 and Lactobacillus
      fermentum RC-14, administered either orally or intravaginally in colonizing the
      vagina and/or preventing the colonization and infection of the vagina by C.
      albicans, while the results of a small number of clinical trials do not
      corroborate these findings. Nevertheless, most of the relevant clinical trials
      had methodological problems such as small sample size, no control group (placebo)
      and included women without confirmed recurrent VVC, and thus they are not
      reliable for drawing definitive conclusions. Thus, the available evidence for the
      use of probiotics for prevention of recurrent VVC is limited. However, the
      empirical use of probiotics may be considered in women with frequent recurrence
      of VVC (more than three episodes per year), especially for those who have adverse
      effects from or contraindications for the use of antifungal agents, since adverse
      effects of probiotics are very rare. In any case women should be clearly informed
      about the unproven usefulness of probiotics for this purpose. In conclusion,
      despite the promising results of some studies, further research is needed to
      prove the effectiveness of probiotics in preventing the recurrences of VVC and to
      allow their wide use for this indication.

PMID- 16790462
TI  - Genetic diversity and geographic differentiation in Tacca chantrieri (Taccaceae):
      an autonomous selfing plant with showy floral display.
AB  - BACKGROUND AND AIMS: Despite considerable investment in elaborate floral
      displays, Tacca chantrieri populations are predominantly selfing. It is
      hypothesized that this species might possess considerable spatial or temporal
      variation in outcrossing rates among populations. To test this hypothesis,
      genetic variability and genetic differentiation within and among T. chantrieri
      populations were investigated to find out if they are in agreement with
      expectations based on a predominantly inbred mating system. METHODS: Genetic
      diversity was quantified using inter-simple sequence repeats (ISSR) in 303
      individuals from 13 populations taken from known locations of T. chantrieri in
      China, and from one population in Thailand. KEY RESULTS: Of the 113 primers
      screened, 24 produced highly reproducible ISSR bands. Using these primers, 160
      discernible DNA fragments were generated, of which 145 (90.62 %) were
      polymorphic. This indicated considerable genetic variation at the species level.
      However, there were relatively low levels of polymorphism at population levels,
      with percentages of polymorphic bands (PPB) ranging from 8.75 % to 55 %. A high
      level of genetic differentiation among populations was detected based on
      different measures (Nei's genetic diversity analysis: G(ST) = 0.5835; AMOVA
      analysis: F(ST) = 0.6989). Furthermore, based on levels of genetic
      differentiation, the 14 populations clustered into two distinct groups separated
      by the Tanaka Line. CONCLUSIONS: High levels of differentiation among populations
      and low levels of diversity within populations at large spatial scales are
      consistent with earlier small-scale studies of mating patterns detected by
      allozymes which showed that T. chantrieri populations are predominantly selfing.
      However, it appears that T. chantrieri has a mixed-mating system in which self
      fertilization predominates, but there is occasional outcrossing. Significant
      genetic differences between the two distinct regions might be attributed to
      vicariance along the Tanaka Line. Finally, possible mechanisms of geographic
      patterns based on genetic differentiation of T. chantrieri are discussed.

PMID- 16790463
TI  - Threatened pollination systems in native flora of the Ogasawara (Bonin) Islands.
AB  - BACKGROUND AND AIMS: Various alien species have been introduced to the Ogasawara
      Islands (Japan). A survey was made investigating whether the native pollination
      systems fit an 'island syndrome' (biasing the flora to dioecy, with subdued,
      inconspicuous flowers) and whether alien species have disrupted the native
      pollination network. METHODS: Flower visitors and floral traits were determined
      in the field (12 islands) and from the literature. Associations among floral
      traits such as sexual expression, flower colour and flower shape were tested. KEY
      RESULTS: Among the 269 native flowering plants, 74.7 % are hermaphroditic, 13.0 %
      are dioecious and 7.1 % are monoecious. Classification by flower colour revealed
      that 36.0 % were white, 21.6 % green and 13.8 % yellow. Woody species (trees and
      shrubs) comprised 36.5 % of the flora and were associated with dioecy and white
      flowers. Solitary, endemic small bees were the dominant flower visitors and
      visited 66.7 % of the observed species on satellite islands where the native
      pollination networks are preserved. In contrast to the situation on the satellite
      islands, introduced honeybees were the most dominant pollinator (visiting 60.1 %
      of observed species) on the two main islands, Chichi-jima and Haha-jima, and had
      spread to satellite islands near Chichi-jima Island. CONCLUSIONS: The island
      syndrome for pollination systems in the Ogasawara Islands was evident in a high
      percentage of dioecious species, the subdued colour of the native flora and
      solitary flower visitors on satellite islands. The shape and colour adaptations
      of several flowers suggested native pollination niches for long-proboscis moths
      and carpenter bees. However, the domination and expansion of introduced honeybees
      have the potential for disruption of the native pollination network in the two
      main, and several satellite, islands of the Ogasawara Islands.

PMID- 16790464
TI  - Accumulation of glycinebetaine in rice plants that overexpress choline
      monooxygenase from spinach and evaluation of their tolerance to abiotic stress.
AB  - BACKGROUND AND AIMS: Glycinebetaine (GB), a quaternary ammonium compound, is a
      very effective compatible solute. In higher plants, GB is synthesized from
      choline (Cho) via betaine aldehyde (BA). The first and second steps in the
      biosynthesis of GB are catalysed by choline monooxygenase (CMO) and by betaine
      aldehyde dehydrogenase (BADH), respectively. Rice (Oryza sativa), which has two
      genes for BADH, does not accumulate GB because it lacks a functional gene for
      CMO. Rice plants accumulate GB in the presence of exogenously applied BA, which
      leads to the development of a significant tolerance to salt, cold and heat
      stress. The goal in this study was to evaluate and to discuss the effects of
      endogenously accumulated GB in rice. METHODS: Transgenic rice plants that
      overexpressed a gene for CMO from spinach (Spinacia oleracea) were produced by
      Agrobacterium-mediated transformation. After Southern and western blotting
      analysis, GB in rice leaves was quantified by (1)H-NMR spectroscopy and the
      tolerance of GB-accumulating plants to abiotic stress was investigated. KEY
      RESULTS: Transgenic plants that had a single copy of the transgene and expressed
      spinach CMO accumulated GB at the level of 0.29-0.43 micromol g(-1) d. wt and had
      enhanced tolerance to salt stress and temperature stress in the seedling stage.
      CONCLUSIONS: In the CMO-expressing rice plants, the localization of spinach CMO
      and of endogenous BADHs might be different and/or the catalytic activity of
      spinach CMO in rice plants might be lower than it is in spinach. These
      possibilities might explain the low levels of GB in the transgenic rice plants.
      It was concluded that CMO-expressing rice plants were not effective for
      accumulation of GB and improvement of productivity.

PMID- 16790466
TI  - Early angiosperm ecology: evidence from the Albian-Cenomanian of Europe.
AB  - BACKGROUND AND AIMS: The mid-Cretaceous is a period of sudden turnover from
      gymnosperm to angiosperm-dominated floras. The aim was to investigate the fossil
      plant ecology in order to follow the spread of angiosperm taxa. METHODS:
      Floristic lists and localities from the latest Albian-Cenomanian of Europe are
      analysed with Wagner's Parsimony Method, a clustering method currently used in
      phylogeny (cladistics). KEY RESULTS: Wagner's Parsimony Method points out that
      (a) gymnosperms dominated brackish water-related environments while angiosperms
      dominated freshwater-related environments (e.g. swamps, floodplains, levees,
      channels), (b) angiosperms showed the highest diversity in stable, freshwater
      related environments, (c) a single angiosperm, 'Diospyros' cretacea, is
      restricted to brackish water-related environments and (d) the families Lauraceae
      and Platanaceae were exclusive to disturbed, braided river environments, implying
      a opportunist strategy for early tree angiosperms. CONCLUSIONS: During the Mid
      Cretaceous, European floras were characterized by (a) coastal gymnosperms, (b)
      highly diversified fluvial angiosperms and (c) the first European brackish water
      related angiosperm.

PMID- 16790467
TI  - Stem phototropism of trees: a possible significant factor in determining stem
      inclination on forest slopes.
AB  - BACKGROUND AND AIMS: The main stems of trees on forest slopes incline down the
      slope to various extents that are characteristic of the species. The inclination
      has been explained as an active response to a horizontally asymmetrical light
      environment, but the contributing physiological mechanisms are unknown. The
      present study tested the hypothesis that stem phototropism, gravitropism, or a
      combination of the two determines the inclination of tree stems on forest slopes.
      METHODS: Cryptomeria japonica, Pinus densiflora, Quercus myrsinaefolia and Q.
      serrata were studied. Measurements were made of stem inclination of mature trees
      on forest slopes in uniform plantations of each species, and changes in stem
      inclination of potted seedlings in response to illumination treatments
      (unilateral or overhead) and inclination treatments (artificially inclined or
      erect). Indices of phototropic and gravitropic responsiveness were evaluated for
      each species, calculated from the change in stem inclination in response to
      artificial inclination with unilateral or overhead illumination. KEY RESULTS:
      Stem inclination on forest slopes varied significantly among species: Q. serrata
      inclined most in the down-slope direction, C. japonica inclined the least, and P.
      densiflora and Q. myrsinaefolia were intermediate. The change in stem inclination
      of seedlings in each treatment varied significantly among species. One-year-old
      stems of Q. serrata and 2-year-old stems of Q. myrsinaefolia bent toward the
      light source. Interspecific variation in the change in stem inclination in
      response to the unilateral illumination or that in the index of phototropic
      responsiveness was strongly correlated with the variation in stem inclination on
      forest slopes. CONCLUSIONS: The orientation of woody stems that have finished
      elongation can be actively controlled by phototropism. Interspecific variation in
      phototropic responsiveness of trees is a possible significant determinant of
      interspecific variation in stem inclination on forest slopes.

PMID- 16790468
TI  - Effect of root system morphology on root-sprouting and shoot-rooting abilities in
      123 plant species from eroded lands in North-east Spain.
AB  - BACKGROUND AND AIMS: The objective of this study was to test whether the mean
      values of several root morphological variables were related to the ability to
      develop root-borne shoots and/or shoot-borne roots in a wide range of vascular
      plants. METHODS: A comparative study was carried out on the 123 most common plant
      species from eroded lands in north-east Spain. After careful excavations in the
      field, measurements were taken of the maximum root depth, absolute and relative
      basal root diameter, specific root length (SRL), and the root depth/root lateral
      spread ratio on at least three individuals per species. Shoot-rooting and root
      sprouting were observed in a large number of individuals in many eroded and
      sedimentary environments. The effect of life history and phylogeny on shoot
      rooting and root-sprouting abilities was also analysed. KEY RESULTS: The species
      with coarse and deep tap-roots tended to be root-sprouting and those with fine,
      fasciculate and long main roots (which generally spread laterally), tended to be
      shoot-rooting. Phylogeny had an important influence on root system morphology and
      shoot-rooting and root-sprouting capacities. However, the above relations stood
      after applying analyses based on phylogenetically independent contrasts (PICs).
      CONCLUSIONS: The main morphological features of the root system of the study
      species are related to their ability to sprout from their roots and form roots
      from their shoots. According to the results, such abilities might only be
      functionally viable in restricted root system morphologies and ecological
      strategies.

PMID- 16790465
TI  - Redox regulatory mechanisms in cellular stress responses.
AB  - BACKGROUND: Reactive oxygen species are produced in a highly localized and
      specific pattern in biological stress responses. The present review examines the
      redox regulatory aspects of a number of molecular stress response mechanisms in
      both prokaryotes and eukaryotes. SCOPE: The present review provides examples
      representing both the cytoplasmic stress response, often studied as the heat
      shock response, as well as the stress response of the endoplasmic reticulum,
      known as the unfolded protein response. The examples have been selected to
      illustrate the variety of ways that redox signals mediate and affect stress
      responses. CONCLUSIONS: Redox regulatory mechanisms are intricately embedded in
      both the cytoplasmic and endoplasmic reticulum stress responses at multiple
      levels. Many different stimuli, both internal and external, activate endogenous
      production of reactive oxygen species as a necessary part of the intracellular
      communication system that activates stress responses.

PMID- 16790469
TI  - Xylem structure and connectivity in grapevine (Vitis vinifera) shoots provides a
      passive mechanism for the spread of bacteria in grape plants.
AB  - BACKGROUND AND AIMS: Bacterial leaf scorch occurring in a number of economically
      important plants is caused by the xylem-limited bacterium Xylella fastidiosa
      (Xf). In grapevine, Xf systemic infection causes Pierce's disease and is lethal.
      Traditional dogma is that Xf movement between vessels requires the digestion of
      inter-vessel pit membranes. However, Yersinia enterocolitica (Ye) (a bacterium
      found in animals) and fluorescent beads moved rapidly within grapevine xylem from
      stem into leaf lamina, suggesting open conduits consisting of long, branched
      xylem vessels for passive movement. This study builds on and expands previous
      observations on the nature of these conduits and how they affect Xf movement.
      METHODS: Air, latex paint and green fluorescence protein (GFP)-Xf were loaded
      into leaves and followed to confirm and identify these conduits. Leaf xylem
      anatomy was studied to determine the basis for the free and sometimes restricted
      movement of Ye, beads, air, paint and GFP-Xf into the lamina. KEY RESULTS:
      Reverse loading experiments demonstrated that long, branched xylem vessels
      occurred exclusively in primary xylem. They were observed in the stem for three
      internodes before diverging into mature leaves. However, this stem-leaf
      connection was an age-dependent character and was absent for the first 10-12
      leaves basal to the apical meristem. Free movement in leaf blade xylem was cell
      type specific with vessels facilitating movement in the body of the blade and
      tracheids near the leaf margin. Air, latex paint and GFP-Xf all moved about 50
      60% of the leaf length. GFP-Xf was never observed close to the leaf margin.
      CONCLUSIONS: The open vessels of the primary xylem offered unimpeded long
      distance pathways bridging stem to leaves, possibly facilitating the spread of
      bacterial pathogens in planta. GFP-Xf never reached the leaf margins where
      scorching appeared, suggesting a signal targeting specific cells or a toxic build
      up at hydathodes.

PMID- 16790470
TI  - Pregnancy-associated plasma protein-A and cardiovascular risk.

PMID- 16790471
TI  - Vascular remodelling after cardiac transplantation: a 3-year serial intravascular
      ultrasound study.
AB  - AIMS: To assess the time-course of intimal hyperplasia and vascular remodelling,
      and their relative contributions on luminal narrowing in transplant coronary
      artery disease (TCAD) by a 3-year serial intravascular ultrasound (IVUS) study.
      METHODS AND RESULTS: Serial IVUS examinations were performed in 90 cardiac
      transplant recipients at 1.4+/-0.6 months after transplantation and again
      annually thereafter for 3 years. From 90 arteries, 304 sites were matched from
      baseline to the third year post-transplant. Based on the change in external
      elastic membrane (EEM) area +/-10% at 1 year, 304 sites were divided into three
      groups: sites with no remodelling (52%); early constrictive remodelling (26%);
      and early compensatory enlargement (22%). Greater intimal growth was seen at 1
      year in sites with early compensatory enlargement, whereas there was no change in
      intimal area in sites with early constrictive remodelling. Over 3 years, the
      cumulative lumen loss was greater in sites with early constrictive remodelling
      than in sites with early compensatory enlargement or no remodelling (P<0.001).
      When luminal narrowing occurred for each annual interval, the contribution from
      the decrease in EEM area was greater than that due to intimal thickening
      (P<0.001). CONCLUSION: During the first 3 years post-transplant, the largest
      intimal growth occurs in the first year, mostly in sites with early compensatory
      enlargement. The contribution to luminal loss in TCAD is greater from
      constrictive remodelling than from intimal hyperplasia. The type of remodelling
      pattern that occurs in transplanted coronary arteries within the first year post
      transplant may be a predictor of the progression of luminal narrowing during
      subsequent years.

PMID- 16790472
TI  - Phylum-wide analysis of SSU rDNA reveals deep phylogenetic relationships among
      nematodes and accelerated evolution toward crown Clades.
AB  - Inference of evolutionary relationships between nematodes is severely hampered by
      their conserved morphology, the high frequency of homoplasy, and the scarcity of
      phylum-wide molecular data. To study the origin of nematode radiation and to
      unravel the phylogenetic relationships between distantly related species, 339
      nearly full-length small-subunit rDNA sequences were analyzed from a diverse
      range of nematodes. Bayesian inference revealed a backbone comprising 12
      consecutive dichotomies that subdivided the phylum Nematoda into 12 clades. The
      most basal clade is dominated by the subclass Enoplia, and members of the order
      Triplonchida occupy positions most close to the common ancestor of the nematodes.
      Crown Clades 8-12, a group formerly indicated as "Secernentea" that includes
      Caenorhabditis elegans and virtually all major plant and animal parasites, show
      significantly higher nucleotide substitution rates than the more basal Clades 1
      7. Accelerated substitution rates are associated with parasitic lifestyles
      (Clades 8 and 12) or short generation times (Clades 9-11). The relatively high
      substitution rates in the distal clades resulted in numerous autapomorphies that
      allow in most cases DNA barcode-based species identification. Teratocephalus, a
      genus comprising terrestrial bacterivores, was shown to be most close to the
      starting point of Secernentean radiation. Notably, fungal feeding nematodes were
      exclusively found basal to or as sister taxon next to the 3 groups of plant
      parasitic nematodes, namely, Trichodoridae, Longidoridae, and Tylenchomorpha. The
      exclusive common presence of fungivorous and plant parasitic nematodes supports a
      long-standing hypothesis that states that plant parasitic nematodes arose from
      fungivorous ancestors.

PMID- 16790473
TI  - The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential
      for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal,
      heart, brain and kidney development.
AB  - Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt
      (sal), cause the autosomal dominant disorder known as Okihiro syndrome. In this
      study, we show that a targeted null mutation in the mouse Sall4 gene leads to
      lethality during peri-implantation. Growth of the inner cell mass from the
      knockout blastocysts was reduced, and Sall4-null embryonic stem (ES) cells
      proliferated poorly with no aberrant differentiation. Furthermore, we
      demonstrated that anorectal and heart anomalies in Okihiro syndrome are caused by
      Sall4 haploinsufficiency and that Sall4/Sall1 heterozygotes exhibited an
      increased incidence of anorectal and heart anomalies, exencephaly and kidney
      agenesis. Sall4 and Sall1 formed heterodimers, and a truncated Sall1 caused
      mislocalization of Sall4 in the heterochromatin; thus, some symptoms of Townes
      Brocks syndrome caused by SALL1 truncations could result from SALL4 inhibition.

PMID- 16790474
TI  - Odd-skipped related 1 is required for development of the metanephric kidney and
      regulates formation and differentiation of kidney precursor cells.
AB  - Formation of kidney tissue requires the generation of kidney precursor cells and
      their subsequent differentiation into nephrons, the functional filtration unit of
      the kidney. Here we report that the gene odd-skipped related 1 (Odd1) plays an
      important role in both these processes. Odd1 is the earliest known marker of the
      intermediate mesoderm, the precursor to all kidney tissue. It is localized to
      mesenchymal precursors within the mesonephric and metanephric kidney and is
      subsequently downregulated upon tubule differentiation. Mice lacking Odd1 do not
      form metanephric mesenchyme, and do not express several other factors required
      for metanephric kidney formation, including Eya1, Six2, Pax2, Sall1 and Gdnf. In
      transient ectopic expression experiments in the chick embryo, Odd1 can promote
      expression of the mesonephric precursor markers Pax2 and Lim1. Finally,
      persistent expression of Odd1 in chick mesonephric precursor cells inhibits
      differentiation of these precursors into kidney tubules. These data indicate that
      Odd1 plays an important role in establishing kidney precursor cells, and in
      regulating their differentiation into kidney tubular tissue.

PMID- 16790475
TI  - The function of growth/differentiation factor 11 (Gdf11) in rostrocaudal
      patterning of the developing spinal cord.
AB  - Hoxc family transcription factors are expressed in different domains along the
      rostrocaudal (RC) axis of the developing spinal cord and they define RC
      identities of spinal neurons. Our previous study using an in vitro assay system
      demonstrated that Fgf and Gdf11 signals located around Hensen's node of chick
      embryos have the ability to induce profiled Hoxc protein expression. To
      investigate the function of Gdf11 in RC patterning of the spinal cord in vivo, we
      expressed Gdf11 in chick embryonic spinal cord by in ovo electroporation and
      found that ectopic expression of Gdf11 in the neural tissue causes a rostral
      displacement of Hoxc protein expression domains, accompanied by rostral shifts in
      the positions of motoneuron columns and pools. Moreover, ectopic expression of
      follistatin (Fst), an antagonist of Gdf11, has a converse effect and causes
      caudal displacement of Hox protein expression domains, as well as motoneuron
      columns and pools. Mouse mutants lacking Gdf11 function exhibit a similar caudal
      displacement of Hox expression domains, but the severity of phenotype increases
      towards the caudal end of the spinal cord, indicating that the function of Gdf11
      is more important in the caudal spinal cord. We also provide evidence that Gdf11
      induces Smad2 phosphorylation and activated Smad2 is able to induce caudal Hox
      gene expression. These results demonstrate that Gdf11 has an important function
      in determining Hox gene expression domains and RC identity in the caudal spinal
      cord.

PMID- 16790476
TI  - Replacement of the Sox10 transcription factor by Sox8 reveals incomplete
      functional equivalence.
AB  - Sox8 and Sox10 are two closely related transcription factors of the Sox protein
      family with overlapping expression patterns during development. They are believed
      to perform very similar functions because several developmental processes,
      including enteric nervous system development and oligodendrocyte differentiation,
      are regulated by both Sox proteins. To analyze the extent of functional
      equivalence between the two Sox proteins, we employed targeted mutagenesis to
      replace Sox10 with Sox8 in the mouse. In mice that expressed Sox8 instead of
      Sox10, Sox10 deficiency was phenotypically rescued to different extents in
      affected tissues. Whereas development of glial cells and neurons in the sensory
      and sympathetic parts of the peripheral nervous system was almost normal when
      Sox10 was replaced by Sox8, melanocyte development was as defective as in Sox10
      deficient mice. The ability of Sox8 to rescue the defects in enteric nervous
      system development and oligodendrocyte differentiation of Sox10-deficient mice
      was limited. We conclude that the extent of functional equivalence depends on the
      tissue and that, despite their relatedness, Sox8 and Sox10 have more unique
      functions than previously appreciated.

PMID- 16790477
TI  - An antagonistic role for the C. elegans Schnurri homolog SMA-9 in modulating
      TGFbeta signaling during mesodermal patterning.
AB  - In C. elegans, the Sma/Mab TGFbeta signaling pathway regulates body size and male
      tail patterning. SMA-9, the C. elegans homolog of Schnurri, has been shown to
      function as a downstream component to mediate the Sma/Mab TGFbeta signaling
      pathway in these processes. We have discovered a new role for SMA-9 in
      dorsoventral patterning of the C. elegans post-embryonic mesoderm, the M lineage.
      In addition to a small body size, sma-9 mutant animals exhibit a dorsal-to
      ventral fate transformation within the M lineage. This M lineage defect of sma-9
      mutants is unique in that animals carrying mutations in all other known
      components of the TGFbeta pathway exhibit no M lineage defects. Surprisingly,
      mutations in the core components of the Sma/Mab TGFbeta signaling pathway
      suppressed the M lineage defects of sma-9 mutants without suppressing their body
      size defects. We show that this suppression specifically happens within the M
      lineage. Our studies have uncovered an unexpected role of SMA-9 in antagonizing
      the TGFbeta signaling pathway during mesodermal patterning, suggesting a novel
      mode of function for the SMA-9/Schnurri family of proteins.

PMID- 16790479
TI  - A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during
      organ of Corti development.
AB  - The molecular mechanisms coordinating cell cycle exit with cell differentiation
      and organogenesis are a crucial, yet poorly understood, aspect of normal
      development. The mammalian cyclin-dependent kinase inhibitor p27(Kip1) is
      required for the correct timing of cell cycle exit in developing tissues, and
      thus plays a crucial role in this process. Although studies of p27(Kip1)
      regulation have revealed important posttranscriptional mechanisms regulating
      p27(Kip1) abundance, little is known about how developmental patterns of
      p27(Kip1) expression, and thus cell cycle exit, are achieved. Here, we show that
      during inner ear development transcriptional regulation of p27(Kip1) is the
      primary determinant of a wave of cell cycle exit that dictates the number of
      postmitotic progenitors destined to give rise to the hair cells and supporting
      cells of the organ of Corti. Interestingly, transcriptional induction from the
      p27(Kip1) gene occurs normally in p27(Kip1)-null mice, indicating that
      developmental regulation of p27(Kip1) transcription is independent of the timing
      of cell cycle exit. In addition, cell-type-specific patterns of p27(Kip1)
      transcriptional regulation are observed in the mature organ of Corti and retina,
      suggesting that this mechanism is important in differential regulation of the
      postmitotic state. This report establishes a link between the spatial and
      temporal pattern of p27(Kip1) transcription and the control of cell number during
      sensory organ morphogenesis.

PMID- 16790478
TI  - Prdm1 acts downstream of a sequential RA, Wnt and Fgf signaling cascade during
      zebrafish forelimb induction.
AB  - Vertebrate limb induction is triggered in the lateral plate mesoderm (LPM) by a
      cascade of signaling events originating in the axial mesoderm. While it is known
      that Fgf, Wnt and retinoic acid (RA) signals are involved in this cascade, their
      precise regulatory hierarchy has not been determined in any species. tbx5 is the
      earliest gene expressed in the limb bud mesenchyme. Recently, another
      transcription factor, Prdm1, has been shown to be crucial for zebrafish forelimb
      development. Here, we show that Prdm1 is downstream of RA, Wnt2b and Tbx5
      activity. We find that RA activity, but not Fgf signaling, is necessary for wnt2b
      expression. Fgf signaling is required for prdm1 expression in the fin bud, but is
      not necessary for the initiation of tbx5 expression. We propose a model in which
      RA signaling from the somitic mesoderm leads to activation of wnt2b expression in
      the intermediate mesoderm, which then signals to the LPM to trigger tbx5
      expression. tbx5 is required for Fgf signaling in the limb bud leading to
      activation of prdm1 expression, which in turn is required for downstream
      activation of fgf10 expression.

PMID- 16790480
TI  - Metastasis-associated kinase modulates Wnt signaling to regulate brain patterning
      and morphogenesis.
AB  - Wnt signaling is a major pathway regulating cell fate determination, cell
      proliferation and cell movements in vertebrate embryos. Distinct branches of this
      pathway activate beta-catenin/TCF target genes and modulate morphogenetic
      movements in embryonic tissues by reorganizing the cytoskeleton. The selection of
      different molecular targets in the pathway is driven by multiple phosphorylation
      events. Here, we report that metastasis-associated kinase (MAK) is a novel
      regulator of Wnt signaling during morphogenetic movements, and eye and brain
      development in Xenopus embryos. Injected MAK RNA suppressed Wnt transcriptional
      reporters and activated Jun N-terminal kinase. Furthermore, MAK was recruited to
      the cell membrane by Frizzled 3, formed a complex with Dishevelled and
      phosphorylated Dsh in vitro. The regional brain markers Otx2, En2 and Gbx2 were
      affected in embryos with modulated MAK activity in a manner consistent with a
      role for MAK in midbrain-hindbrain boundary formation. Confirming the inhibitory
      role for this kinase in Wnt/beta-catenin signaling, the midbrain patterning
      defects in embryos depleted of MAK were rescued by the simultaneous depletion of
      beta-catenin. These findings indicate that MAK may function in different
      developmental processes as a switch between the canonical and non-canonical
      branches of Wnt signaling.

PMID- 16790481
TI  - The roof plate regulates cerebellar cell-type specification and proliferation.
AB  - During embryogenesis, the isthmic organizer, a well-described signaling center at
      the junction of the mid-hindbrain, establishes the cerebellar territory along the
      anterior/posterior axis of the neural tube. Mechanisms specifying distinct
      populations within the early cerebellar anlage are less defined. Using a newly
      developed gene expression map of the early cerebellar anlage, we demonstrate that
      secreted signals from the rhombomere 1 roof plate are both necessary and
      sufficient for specification of the adjacent cerebellar rhombic lip and its
      derivative fates. Surprisingly, we show that the roof plate is not absolutely
      required for initial specification of more distal cerebellar cell fates, but
      rather regulates progenitor proliferation and cell position within the cerebellar
      anlage. Thus, in addition to the isthmus, the roof plate represents an important
      signaling center controlling multiple aspects of cerebellar patterning.

PMID- 16790482
TI  - Surgical treatment of partial tears of the proximal origin of the hamstring
      muscles.
AB  - BACKGROUND: Hamstring injuries are common especially in athletes. Partial and
      complete tears of the proximal origin may cause pain and functional loss.
      OBJECTIVE: To evaluate the results of surgical treatment for partial proximal
      hamstring tears. METHODS: Between 1994 and 2005, 47 athletes (48 cases, 1
      bilateral) with partial proximal hamstring tears were operated on. The cases were
      retrospectively analysed. Before surgery, 42 of the patients had undergone
      conservative treatment with unsatisfactory results, whereas in five patients the
      operation was performed within four weeks of the injury. RESULTS: The mean length
      of the follow up was 36 months (range 6-72). The result of the operation was
      rated excellent in 33 cases, good in nine, fair in four, and poor in two. Forty
      one patients were able to return to their former level of sport after an average
      of five months (range 1-12). CONCLUSION: In most cases, excellent or good results
      can be expected after surgical repair of partial proximal hamstring tears even
      after conservative treatment has failed.

PMID- 16790483
TI  - Rib impingement in first class cricketers: case reports of two patients who
      underwent rib resection.
AB  - Two first class cricket bowlers presented with costoiliac pain secondary to rib
      impingement. In both patients, conservative management of the injury had failed
      to improve symptoms. Surgical resection of the affected rib was undertaken. At
      follow up, both patients had made a good recovery and had returned to competitive
      cricket.

PMID- 16790484
TI  - Efficacy of a tart cherry juice blend in preventing the symptoms of muscle
      damage.
AB  - BACKGROUND: Numerous antioxidant and anti-inflammatory agents have been
      identified in tart cherries. OBJECTIVE: To test the efficacy of a tart cherry
      juice blend in preventing the symptoms of exercise induced muscle damage.
      METHODS: This was a randomised, placebo controlled, crossover design. Fourteen
      male college students drank 12 fl oz of a cherry juice blend or a placebo twice a
      day for eight consecutive days. A bout of eccentric elbow flexion contractions (2
      x 20 maximum contractions) was performed on the fourth day of supplementation.
      Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow
      angle were recorded before and for four days after the eccentric exercise. The
      protocol was repeated two weeks later with subjects who took the placebo
      initially, now taking the cherry juice (and vice versa). The opposite arm
      performed the eccentric exercise for the second bout to avoid the repeated bout
      protective effect. RESULTS: Strength loss and pain were significantly less in the
      cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p =
      0.017). Relaxed elbow angle (time by treatment p = 0.85) and muscle tenderness
      (time by treatment p = 0.81) were not different between trials. CONCLUSIONS:
      These data show efficacy for this cherry juice in decreasing some of the symptoms
      of exercise induced muscle damage. Most notably, strength loss averaged over the
      four days after eccentric exercise was 22% with the placebo but only 4% with the
      cherry juice.

PMID- 16790485
TI  - Validity of the inexpensive Stepping Meter in counting steps in free living
      conditions: a pilot study.
AB  - OBJECTIVES: To evaluate if inexpensive Stepping Meters are valid in counting
      steps in adults in free living conditions. METHODS: For six days, 35 healthy
      volunteers wore a criterion Yamax Digiwalker and five Stepping Meters every day
      until all 973 pedometers had been tested. Steps were recorded daily, and the
      differences between counts from the Digiwalker and the Stepping Meter were
      expressed as a percentage of the valid value of the Digiwalker step counts. The
      criterion used to determine if a Stepping Meter was valid was a maximum deviation
      of 10% from the Digiwalker step counts. RESULTS: A total of 252 (25.9%) Stepping
      Meters met the criterion, whereas 74.1% made an overestimation or underestimation
      of more than 10%. In more than one third (36.6%) of the invalid Stepping Meters,
      the deviation was greater than 50%. Most (64.8%) of the invalid pedometers
      overestimated the actual steps taken. CONCLUSIONS: Inexpensive Stepping Meters
      cannot be used in community interventions as they will give participants the
      wrong message.

PMID- 16790486
TI  - A developmental role for ataxia-telangiectasia mutated in protecting the embryo
      from spontaneous and phenytoin-enhanced embryopathies in culture.
AB  - Ataxia-telangiectasia (A-T) is characterized by impaired recognition and repair
      of DNA damage and increased sensitivity to ionizing radiation (IR), cancer, and
      neurodegeneration. We previously showed pregnant knockout mice lacking the A-T
      gene product ataxia-telangiectasia mutated (Atm) are highly susceptible to the
      embryopathic effects of IR, which damages DNA, possibly via generation of
      reactive oxygen species (ROS). Here we show that Atm more broadly protects
      against both spontaneous and phenytoin-enhanced embryopathies. In the absence of
      drug exposure, cultured embryos from pregnant Atm knockout mice showed more
      embryopathies than wild-type littermates, with a gene dose-dependent decrease in
      susceptibility from -/- to +/- to +/+ embryos (p < 0.05). A similar but
      significantly enhanced gene dose-dependent pattern of embryopathic susceptibility
      was evident in Atm knockout embryos exposed to the ROS-initiating teratogen
      phenytoin (p < 0.05). These results provide the first evidence that Atm has a
      broad developmental importance beyond IR embryopathies, possibly by protecting
      the embryo from constitutive and xenobiotic-enhanced oxidative stress, with even
      heterozygotes showing increased risk. This developmental role of Atm further
      implicates DNA damage in ROS-mediated teratogenesis and DNA damage response and
      repair as risk factors for individual susceptibility.

PMID- 16790487
TI  - The common insecticides cyfluthrin and chlorpyrifos alter the expression of a
      subset of genes with diverse functions in primary human astrocytes.
AB  - Given the widespread use of insecticides in the environment, it is important to
      perform studies evaluating their potential effects on humans. Organophosphate
      insecticides, such as chlorpyrifos, are being phased out; however, the use of
      pyrethroids in household pest control is increasing. While chlorpyrifos is
      relatively well studied, much less is known about the potential neurotoxicity of
      cyfluthrin and other pyrethroids. To gain insights into the neurotoxicity of
      cyfluthrin, we compared and evaluated the toxicity profiles of chlorpyrifos and
      cyfluthrin in primary human fetal astrocytes. We found that at the same
      concentrations, cyfluthrin exerts as great as, or greater toxic effects on the
      growth, survival, and proper functioning of human astrocytes. By using microarray
      gene expression profiling, we systematically identified and compared the
      potential molecular targets of chlorpyrifos and cyfluthrin, at a genome-wide
      scale. We found that chlorpyrifos and cyfluthrin affect a similar number of
      transcripts. These targets include molecular chaperones, signal transducers,
      transcriptional regulators, transporters, and those involved in behavior and
      development. Further computational and biochemical analyses show that cyfluthrin
      and chlorpyrifos upregulate certain targets of the interferon-gamma and insulin
      signaling pathways and that they increase the protein levels of activated
      extracellular signal-regulated kinase 1/2, a key component of insulin signaling;
      interleukin 6, a key inflammatory mediator; and glial fibrillary acidic protein,
      a marker of inflammatory astrocyte activation. These results suggest that
      inflammatory activation of astrocytes might be an important mechanism underlying
      neurotoxicity of both chlorpyrifos and cyfluthrin.

PMID- 16790488
TI  - Estrogen-like response to p-nonylphenol in human first trimester placenta and
      BeWo choriocarcinoma cells.
AB  - p-Nonylphenol (p-NP) is a metabolite of alkylphenol ethoxylates used as
      surfactants in the manufacturing industry. Although it is reported to have
      estrogenic activity and to be transferred from the mother to the embryo, no data
      are available on its effects on the development of the human placenta. In the
      present study, we investigated estrogen receptors' (ERs) expression in the first
      trimester human placenta. Using an in vitro model of chorionic villous explants,
      we then compared the effects of p-NP and 17beta-estradiol (17beta-E2). Finally, a
      trophoblast-derived choriocarcinoma cell line, BeWo, was used as a model of
      trophoblast cell differentiation. Our results showed that the first trimester
      placenta expresses three ER-alpha isoforms of 67, 46, and 39 kDa and one ER-beta
      isoform of 55 kDa. Immunohistochemistry revealed the expression of ER-alpha in
      the villous cytotrophoblast, whereas ER-beta was mainly expressed by the
      syncytiotrophoblast. Treatment of explant cultures with p-NP (10(-9)M) and 17beta
      E2 (10(-9)M) significantly increased beta-hCG secretion and cell apoptosis but
      did not modify ER expression. After 72 h of exposure, hormone release was
      significantly higher in p-NP- than 17beta-E2-treated explant cultures. By this
      time, cleavage of caspase-3 was evident in cultures treated with 17beta-E2 and p
      NP. In BeWo cells, a caspase-3 band of 20-16 kDa was evident after 1 h of
      treatment with p-NP and after 24 h of treatment with 17beta-E2 or forskolin.
      These findings suggest that the human trophoblast may be highly responsive to p
      NP and raise concern about maternal exposure in early gestation.

PMID- 16790489
TI  - Hepatic biotransformation and metabolite profile during a 2-week depuration
      period in Atlantic salmon fed graded levels of the synthetic antioxidant,
      ethoxyquin.
AB  - The synthetic antioxidant ethoxyquin (EQ) is increasingly used in animal feeds
      and has been candidate for carcinogenicity testing. EQ has the potential for
      toxicological and adverse health effects for both fish and fish consumers through
      "carryover" processes. The toxicological aspects of EQ have not been
      systematically investigated. The present study was performed to investigate the
      hepatic metabolism, metabolite characterization, and toxicological aspects of EQ
      in salmon during a 2-week depuration after a 12-week feeding period with 18 mg
      (low), 107 mg (medium), and 1800 mg/kg feed (high). The alteration in gene
      expressions and catalytic activities of hepatic biotransformation enzymes were
      studied using real-time polymerase chain reaction with specific primer pairs and
      by kinetics of two identified hepatic metabolites. Analysis of EQ metabolism was
      performed using high performance liquid chromatography (HPLC) method and showed
      the detection of four compounds of which two were quantified, parent EQ and EQ
      dimer (EQDM). Two metabolites were identified as de-ethylated EQ (DEQ) and
      quinone imine, but these were not quantified. The concentration of the quantified
      EQ-related compounds in the liver at day 0 showed a positive linear relationship
      with measured dietary EQ (R2= 0.86 and 0.92 for parent EQ and EQDM,
      respectively). While the low-EQ-feeding group showed a time-specific increase of
      aryl hydrocarbon receptor (AhR) mRNA expression, the medium-dose group showed
      decreased AhR mRNA at depuration day 7. Expression of CYP1A1 was decreased during
      the depuration period. Consumption of dietary EQ produced the expression of
      CYP3A, glutathione S-transferase (GST), and uridine diphosphate glucuronosyl
      transferase (UDPGT) mRNA during the depuration period. A similar pattern of
      effect was observed for both CYP3A and phase II genes and supports our previous
      postulation of common regulation of these enzymes by the same inducer, namely EQ
      metabolites. The increase of CYP3A, UDPGT, and GST gene expressions at day 7 was
      in accordance with the low concentration of DEQ. The low concentration of
      putative DEQ may induce the CYP3A with subsequent increase in the
      biotransformation of EQ into DEQ. The increase in UDPGT may seem to be a
      synchronizing mechanism required for the excretion of DEQ. The biotransformation
      of dietary EQ is proven by simultaneous induction of both phase I and II
      detoxification system in the liver of Atlantic salmon. Therefore, the apparent
      low concentration of putative DEQ may account for the induced phase I and II
      detoxifying enzymes at least during depuration. This speculated hypothesis is
      currently a subject for systematic investigation in our laboratory using in vitro
      and genomic approaches.

PMID- 16790490
TI  - Cigarette smoke toxicants alter growth and survival of cultured mammalian cells.
AB  - Our purpose was to determine the effects of six cigarette toxicants (pyridine,
      nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three
      types of cultured mammalian cells (human umbilical vein endothelial cells
      [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells)
      using a cell proliferation/survival assay. Synchronized cells were cultured in
      proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of
      the tested chemicals. After 48 h, cells were counted using a hemacytometer. The
      no observable adverse effect level (NOAEL), lowest observable adverse effect
      level (LOAEL), and the efficacy were determined for each compound in the cell
      proliferation and survival assays. Pyridine and p-cresol did not show significant
      effects with any cell types, except at high doses. Derivitization of the pyridine
      ring altered its potency, especially when an ethyl group or nitrogen was added.
      In survival medium, nicotine stimulated proliferation of all three cell types at
      doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2
      ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in
      proliferation medium and induced cell death in survival medium at attomolar and
      femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3
      cell proliferation at low doses and induced cell death at high doses. LOAELs and
      efficacies revealed that endothelial cells from a developing organ (umbilical
      cord) were more sensitive to these chemicals than endothelial cells from an adult
      organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low
      doses, are added to consumer products and should be subjected to further
      toxicological testing.

PMID- 16790491
TI  - Distinct roles for TGN/endosome epsin-like adaptors Ent3p and Ent5p.
AB  - Clathrin adaptors are key factors in clathrin-coated vesicle formation, coupling
      clathrin to cargo and/or the lipid bilayer. A physically interacting network of
      three classes of adaptors participate in clathrin-mediated traffic between the
      trans-Golgi network (TGN) and endosomes: AP-1, Gga proteins, and epsin-like
      proteins. Here we investigate functional relationships within this network
      through transport assays and protein localization analysis in living yeast cells.
      We observed that epsin-like protein Ent3p preferentially localized with Gga2p,
      whereas Ent5p distributed equally between AP-1 and Gga2p. Ent3p was mislocalized
      in Gga-deficient but not in AP-1-deficient cells. In contrast, Ent5p retained
      localization in cells lacking either or both AP-1 and Gga proteins. The Ent
      proteins were dispensable for AP-1 or Gga localization. Synthetic genetic growth
      and alpha-factor maturation defects were observed when ent5Delta but not
      ent3Delta was introduced together with deletions of the GGA genes. In AP-1
      deficient cells, ent3Delta and to a lesser extent ent5Delta caused minor alpha
      factor maturation defects, but together resulted in a near-lethal phenotype.
      Deletions of ENT3 and ENT5 also displayed synthetic defects similar to, but less
      severe than, synthetic effects of AP-1 and Gga inactivation. These results
      differentiate Ent3p and Ent5p function in vivo, suggesting that Ent3p acts
      primarily with Gga proteins, whereas Ent5p acts with both AP-1 and Gga proteins
      but is more critical for AP-1-mediated transport. The data also support a model
      in which the Ent adaptors provide important accessory functions to AP-1 and Gga
      proteins in TGN/endosome traffic.

PMID- 16790492
TI  - Guanylyl cyclase protein and cGMP product independently control front and back of
      chemotaxing Dictyostelium cells.
AB  - Chemotaxis of amoeboid cells is driven by actin filaments in leading pseudopodia
      and actin-myosin filaments in the back and at the side of the cell to suppress
      pseudopodia. In Dictyostelium, cGMP plays an important role during chemotaxis and
      is produced predominantly by a soluble guanylyl cyclase (sGC). The sGC protein is
      enriched in extending pseudopodia at the leading edge of the cell during
      chemotaxis. We show here that the sGC protein and the cGMP product have different
      functions during chemotaxis, using two mutants that lose either catalytic
      activity (sGCDelta cat) or localization to the leading edge (sGCDeltaN). Cells
      expressing sGCDeltaN exhibit excellent cGMP formation and myosin localization in
      the back of the cell, but they exhibit poor orientation at the leading edge.
      Cells expressing the catalytically dead sGCDelta cat mutant show poor myosin
      localization at the back, but excellent localization of the sGC protein at the
      leading edge, where it enhances the probability that a new pseudopod is made in
      proximity to previous pseudopodia, resulting in a decrease of the degree of
      turning. Thus cGMP suppresses pseudopod formation in the back of the cell,
      whereas the sGC protein refines pseudopod formation at the leading edge.

PMID- 16790493
TI  - Characterization of Mmp37p, a Saccharomyces cerevisiae mitochondrial matrix
      protein with a role in mitochondrial protein import.
AB  - Many mitochondrial proteins are encoded by nuclear genes and after translation in
      the cytoplasm are imported via translocases in the outer and inner membranes, the
      TOM and TIM complexes, respectively. Here, we report the characterization of the
      mitochondrial protein, Mmp37p (YGR046w) and demonstrate its involvement in the
      process of protein import into mitochondria. Haploid cells deleted of MMP37 are
      viable but display a temperature-sensitive growth phenotype and are inviable in
      the absence of mitochondrial DNA. Mmp37p is located in the mitochondrial matrix
      where it is peripherally associated with the inner membrane. We show that Mmp37p
      has a role in the translocation of proteins across the mitochondrial inner
      membrane via the TIM23-PAM complex and further demonstrate that substrates
      containing a tightly folded domain in close proximity to their mitochondrial
      targeting sequences display a particular dependency on Mmp37p for mitochondrial
      import. Prior unfolding of the preprotein, or extension of the region between the
      targeting signal and the tightly folded domain, relieves their dependency for
      Mmp37p. Furthermore, evidence is presented to show that Mmp37 may affect the
      assembly state of the TIM23 complex. On the basis of these findings, we
      hypothesize that the presence of Mmp37p enhances the early stages of the TIM23
      matrix import pathway to ensure engagement of incoming preproteins with the
      mtHsp70p/PAM complex, a step that is necessary to drive the unfolding and
      complete translocation of the preprotein into the matrix.

PMID- 16790494
TI  - The novel F-box protein Mfb1p regulates mitochondrial connectivity and exhibits
      asymmetric localization in yeast.
AB  - Although it is clear that mitochondrial morphogenesis is a complex process
      involving multiple proteins in eukaryotic cells, little is known about regulatory
      molecules that modulate mitochondrial network formation. Here, we report the
      identification of a new yeast mitochondrial morphology gene called MFB1
      (YDR219C). MFB1 encodes an F-box protein family member, many of which function in
      Skp1-Cdc53/Cullin-F-box protein (SCF) ubiquitin ligase complexes. F-box proteins
      also act in non-SCF complexes whose functions are not well understood. Although
      cells lacking Mfb1p contain abnormally short mitochondrial tubules, Mfb1p is not
      essential for known pathways that determine mitochondrial morphology and
      dynamics. Mfb1p is peripherally associated with the mitochondrial surface.
      Coimmunoprecipitation assays reveal that Mfb1p interacts with Skp1p in an F-box
      dependent manner. However, Mfb1p does not coimmunoprecipitate with Cdc53p. The F
      box motif is not essential for Mfb1p-mediated mitochondrial network formation.
      These observations suggest that Mfb1p acts in a complex lacking Cdc53p required
      for mitochondrial morphogenesis. During budding, Mfb1p asymmetrically localizes
      to mother cell mitochondria. By contrast, Skp1p accumulates in the daughter cell
      cytoplasm. Mfb1p mother cell-specific asymmetry depends on the F-box motif,
      suggesting that Skp1p down-regulates Mfb1p mitochondrial association in buds. We
      propose that Mfb1p operates in a novel pathway regulating mitochondrial tubular
      connectivity.

PMID- 16790495
TI  - Caenorhabditis elegans UNC-96 is a new component of M-lines that interacts with
      UNC-98 and paramyosin and is required in adult muscle for assembly and/or
      maintenance of thick filaments.
AB  - To gain further insight into the molecular architecture, assembly, and
      maintenance of the sarcomere, we have carried out a molecular analysis of the UNC
      96 protein in the muscle of Caenorhabditis elegans. By polarized light microscopy
      of body wall muscle, unc-96 mutants display reduced myofibrillar organization and
      characteristic birefringent "needles." By immunofluorescent staining of known
      myofibril components, unc-96 mutants show major defects in the organization of M
      lines and in the localization of a major thick filament component, paramyosin. In
      unc-96 mutants, the birefringent needles, which contain both UNC-98 and
      paramyosin, can be suppressed by starvation or by exposure to reduced
      temperature. UNC-96 is a novel approximately 47-kDa polypeptide that has no
      recognizable domains. Antibodies generated to UNC-96 localize the protein to the
      M-line, a region of the sarcomere in which thick filaments are cross-linked. By
      genetic and biochemical criteria, UNC-96 interacts with UNC-98, a previously
      described component of M-lines, and paramyosin. Additionally, UNC-96 copurifies
      with native thick filaments. A model is presented in which UNC-96 is required in
      adult muscle to promote thick filament assembly and/or maintenance.

PMID- 16790497
TI  - Cep55, a microtubule-bundling protein, associates with centralspindlin to control
      the midbody integrity and cell abscission during cytokinesis.
AB  - We report here an efficient functional genomic analysis by combining information
      on the gene expression profiling, cellular localization, and loss-of-function
      studies. Through this analysis, we identified Cep55 as a regulator required for
      the completion of cytokinesis. We found that Cep55 localizes to the mitotic
      spindle during prometaphase and metaphase and to the spindle midzone and the
      midbody during anaphase and cytokinesis. At the terminal stage of cytokinesis,
      Cep55 is required for the midbody structure and for the completion of
      cytokinesis. In Cep55-knockdown cells, the Flemming body is absent, and the
      structural and regulatory components of the midbody are either absent or
      mislocalized. Cep55 also facilitates the membrane fusion at the terminal stage of
      cytokinesis by controlling the localization of endobrevin, a v-SNARE required for
      cell abscission. Biochemically, Cep55 is a microtubule-associated protein that
      efficiently bundles microtubules. Cep55 directly binds to MKLP1 in vitro and
      associates with the MKLP1-MgcRacGAP centralspindlin complex in vivo. Cep55 is
      under the control of centralspindlin, as knockdown of centralspindlin abolished
      the localization of Cep55 to the spindle midzone. Our study defines a cellular
      mechanism that links centralspindlin to Cep55, which, in turn, controls the
      midbody structure and membrane fusion at the terminal stage of cytokinesis.

PMID- 16790496
TI  - Nonredundant roles of mitochondria-associated F-box proteins Mfb1 and Mdm30 in
      maintenance of mitochondrial morphology in yeast.
AB  - Mitochondria constantly fuse and divide to adapt organellar morphology to the
      cell's ever-changing physiological conditions. Little is known about the
      molecular mechanisms regulating mitochondrial dynamics. F-box proteins are
      subunits of both Skp1-Cullin-F-box (SCF) ubiquitin ligases and non-SCF complexes
      that regulate a large number of cellular processes. Here, we analyzed the roles
      of two yeast F-box proteins, Mfb1 and Mdm30, in mitochondrial dynamics. Mfb1 is a
      novel mitochondria-associated F-box protein. Mitochondria in mutants lacking Mfb1
      are fusion competent, but they form aberrant aggregates of interconnected
      tubules. In contrast, mitochondria in mutants lacking Mdm30 are highly fragmented
      due to a defect in mitochondrial fusion. Fragmented mitochondria are docked but
      nonfused in Deltamdm30 cells. Mitochondrial fusion is also blocked during
      sporulation of homozygous diploid mutants lacking Mdm30, leading to a
      mitochondrial inheritance defect in ascospores. Mfb1 and Mdm30 exert nonredundant
      functions and likely have different target proteins. Because defects in F-box
      protein mutants could not be mimicked by depletion of SCF complex and proteasome
      core subunits, additional yet unknown factors are likely involved in regulating
      mitochondrial dynamics. We propose that mitochondria-associated F-box proteins
      Mfb1 and Mdm30 are key components of a complex machinery that regulates
      mitochondrial dynamics throughout yeast's entire life cycle.

PMID- 16790498
TI  - Involvement of syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE
      protein, in ER-mediated phagocytosis.
AB  - The endoplasmic reticulum (ER) is thought to play an important structural and
      functional role in phagocytosis. According to this model, direct membrane fusion
      between the ER and the plasma or phagosomal membrane must precede further
      invagination, but the exact mechanisms remain elusive. Here, we investigated
      whether various ER-localized SNARE proteins are involved in this fusion process.
      When phagosomes were isolated from murine J774 macrophages, we found that ER
      localized SNARE proteins (syntaxin 18, D12, and Sec22b) were significantly
      enriched in the phagosomes. Fluorescence and immuno-EM analyses confirmed the
      localization of syntaxin 18 in the phagosomal membranes of J774 cells stably
      expressing this protein tagged to a GFP variant. To examine whether these SNARE
      proteins are required for phagocytosis, we generated 293T cells stably expressing
      the Fc gamma receptor, in which phagocytosis occurs in an IgG-mediated manner.
      Expression in these cells of dominant-negative mutants of syntaxin 18 or D12
      lacking the transmembrane domain, but not a Sec22b mutant, impaired phagocytosis.
      Syntaxin 18 small interfering RNA (siRNA) selectively decreased the efficiency of
      phagocytosis, and the rate of phagocytosis was markedly enhanced by stable
      overexpression of syntaxin 18 in J774 cells. Therefore, we conclude that syntaxin
      18 is involved in ER-mediated phagocytosis, presumably by regulating the specific
      and direct fusion of the ER and plasma or phagosomal membranes.

PMID- 16790499
TI  - NAADP as a second messenger: neither CD38 nor base-exchange reaction are
      necessary for in vivo generation of NAADP in myometrial cells.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) has recently been shown to
      act as a second messenger controlling intracellular Ca(2+) responses in mammalian
      cells. Many questions remain regarding this signaling pathway, including the role
      of the ryanodine receptor (RyR) in NAADP-induced Ca(2+) transients. Furthermore,
      the exact metabolic pathway responsible for the synthesis of NAADP in vivo has
      not been determined. Here, we demonstrate that the NAADP mediated Ca(2+) release
      system is present in human myometrial cells. We also demonstrate that human
      myometrial cells use the NAADP second messenger system to generate intracellular
      Ca(2+) transients in response to histamine. It has been proposed in the past that
      the NAADP system in mammalian cells is dependent on the presence of functional
      RyRs. Here, we observed that the histamine-induced Ca(2+) transients are
      dependent on both the NAADP and inositol 1,4,5-trisphosphate signaling pathways
      but are independent of RyRs. The enzyme CD38 has been shown to catalyze the
      synthesis of NAADP in vitro by the base-exchange reaction. Furthermore, it has
      been proposed that this enzyme is responsible for the intracellular generation of
      NAADP in vivo. Using CD38 knockout mice, we observed that both the basal and
      histamine stimulated levels of NAADP are independent of CD38 and the base
      exchange reaction. Our group is the first to demonstrate that NAADP is a second
      messenger for histamine-elicited Ca(2+) transients in human myometrial cells.
      Furthermore, the NAADP mediated mechanism in mammalian cells can be independent
      of RyRs and CD38. Our data provides novel insights into the understanding of the
      mechanism of action and metabolism of this new second messenger system.

PMID- 16790500
TI  - Neuregulin-dependent protein synthesis in C2C12 myotubes and rat diaphragm
      muscle.
AB  - The nerve-derived trophic factor neuregulin (NRG) is a prime candidate molecule
      for modulating muscle fiber growth. NRG regulates signal transduction in skeletal
      muscle through activation of ErbB receptors present at the neuromuscular
      junction. In this study, we hypothesize that NRG increases protein synthesis in
      maturing muscle via a phosphatidylinositol 3-kinase (PI3K)-dependent mechanism.
      NRG signal transduction and its ability to stimulate protein synthesis (measured
      by incorporation of [(3)H]phenylalanine into the protein pool) were investigated
      in differentiated C(2)C(12) myotubes and rat diaphragm muscle (DIAm). In
      C(2)C(12) myotubes, NRG dose dependently increased phosphorylation of ErbB3 and
      recruitment of the p85 subunit of PI3K. NRG also increased phosphorylation of
      Akt, a downstream effector of PI3K. NRG treatment increased total protein
      synthesis by 35% compared with untreated control myotubes. This NRG-induced
      increase in Akt phosphorylation and protein synthesis was completely blocked by
      wortmannin, an inhibitor of PI3K but was unaffected by PD-98059, an inhibitor of
      MEK. In DIAm obtained from 3-day-old rat pups, Akt phosphorylation increased
      approximately 30-fold with NRG treatment (vs. untreated DIAm). NRG treatment also
      significantly increased protein synthesis in the DIAm by 29% after 3 h of
      incubation with [(3)H]phenylalanine (vs. untreated DIAm). Pretreatment with
      wortmannin abolished the NRG-induced increase in protein synthesis, suggesting a
      critical role for PI3K in this response. The results of the present study support
      the hypothesis that nerve-derived NRG contributes to the regulation of skeletal
      muscle mass by increasing protein synthesis via activation of PI3K.

PMID- 16790501
TI  - Human esophageal microvascular endothelial cells respond to acidic pH stress by
      PI3K/AKT and p38 MAPK-regulated induction of Hsp70 and Hsp27.
AB  - The heat shock response maintains cellular homeostasis following sublethal
      injury. Heat shock proteins (Hsps) are induced by thermal, oxyradical, and
      inflammatory stress, and they chaperone denatured intracellular proteins. Hsps
      also chaperone signal transduction proteins, modulating signaling cascades during
      repeated stress. Gastroesophageal reflux disease (GERD) affects 7% of the US
      population, and it is linked to prolonged esophageal acid exposure. GERD is
      characterized by enhanced and selective leukocyte recruitment from esophageal
      microvasculature, implying activation of microvascular endothelium. We
      investigated whether phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK regulate
      Hsp induction in primary cultures of human esophageal microvascular endothelial
      cells (HEMEC) in response to acid exposure (pH 4.5). Inhibitors of signaling
      pathways were used to define the contribution of PI3K/Akt and MAPKs in the heat
      shock response and following acid exposure. Acid significantly enhanced
      phosphorylation of Akt and MAPKs in HEMEC as well as inducing Hsp27 and Hsp70.
      The PI3K inhibitor LY-294002, and Akt small interfering RNA inhibited Akt
      activation and Hsp70 expression in HEMEC. The p38 MAPK inhibitor (SB-203580) and
      p38 MAPK siRNA blocked Hsp27 and Hsp70 mRNA induction, suggesting a role for
      MAPKs in the HEMEC heat shock response. Thus acidic pH exposure protects HEMEC
      through induction of Hsps and activation of MAPK and PI3 kinase pathway. Acidic
      exposure increased HEMEC expression of VCAM-1 protein, but not ICAM-1, which may
      contribute to selective leukocyte (i.e., eosinophil) recruitment in esophagitis.
      Activation of esophageal endothelial cells exposed to acidic refluxate may
      contribute to GERD in the setting of a disturbed mucosal squamous epithelial
      barrier (i.e., erosive esophagitis, peptic ulceration).

PMID- 16790502
TI  - Calpain 10: a mitochondrial calpain and its role in calcium-induced mitochondrial
      dysfunction.
AB  - Calpains, Ca(2+)-activated cysteine proteases, are cytosolic enzymes implicated
      in numerous cellular functions and pathologies. We identified a mitochondrial
      Ca(2+)-inducible protease that hydrolyzed a calpain substrate (SLLVY-AMC) and was
      inhibited by active site-directed calpain inhibitors as calpain 10, an atypical
      calpain lacking domain IV. Immunoblot analysis and activity assays revealed
      calpain 10 in the mitochondrial outer membrane, intermembrane space, inner
      membrane, and matrix fractions. Mitochondrial staining was observed when COOH
      terminal green fluorescent protein-tagged calpain 10 was overexpressed in NIH-3T3
      cells and the mitochondrial targeting sequence was localized to the NH(2)
      terminal 15 amino acids. Overexpression of mitochondrial calpain 10 resulted in
      mitochondrial swelling and autophagy that was blocked by the mitochondrial
      permeability transition (MPT) inhibitor cyclosporine A. With the use of isolated
      mitochondria, Ca(2+)-induced MPT was partially decreased by calpain inhibitors.
      More importantly, Ca(2+)-induced inhibition of Complex I of the electron
      transport chain was blocked by calpain inhibitors and two Complex I proteins were
      identified as targets of mitochondrial calpain 10, NDUFV2, and ND6. In
      conclusion, calpain 10 is the first reported mitochondrially targeted calpain and
      is a mediator of mitochondrial dysfunction through the cleavage of Complex I
      subunits and activation of MPT.

PMID- 16790503
TI  - Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine
      transport via hTHTR2: biotin is not a substrate for hTHTR2.
AB  - The water-soluble micronutrient thiamine is required for normal tissue growth and
      development in humans. Thiamine is accumulated into cells through the activity of
      two cell surface thiamine transporters (hTHTR1 and hTHTR2), which are
      differentially targeted in polarized tissues. Mutational dysfunction of hTHTR1 is
      associated with the clinical condition of thiamine-responsive megaloblastic
      anemia: the symptoms of which are alleviated by thiamine supplementation.
      Recently, two hTHTR2 mutants (G23V, T422A) have been discovered in clinical
      kindreds manifesting biotin-responsive basal ganglia disease (BBGD): the symptoms
      of which are alleviated by biotin administration. Why then does mutation of a
      specific thiamine transporter isoform precipitate a disorder correctable by
      exogenous biotin? To investigate the suggestion that hTHTR2 can physiologically
      function as a biotin transporter, we examined 1) the cell biological basis of
      hTHTR2 dysfunction associated with the G23V and T422A mutations and 2) the
      substrate specificity of hTHTR2 and these clinically relevant mutants. We show
      that the G23V and T422A mutants both abrogate thiamine transport activity rather
      than targeting of hTHTR2 to the cell surface. Furthermore, biotin accumulation
      was not detectable in cells overexpressing either the full length hTHTR2 or the
      clinically relevant hTHTR2 mutants, yet was demonstrable in the same assay using
      cells overexpressing the human sodium-dependent multivitamin transporter, a known
      biotin transporter. These results cast doubt on the most parsimonious explanation
      for the BBGD phenotype, namely that hTHTR2 is a physiological biotin transporter.

PMID- 16790504
TI  - Characterization of transport mechanisms and determinants critical for Na+
      dependent Pi symport of the PiT family paralogs human PiT1 and PiT2.
AB  - The general phosphate need in mammalian cells is accommodated by members of the
      P(i) transport (PiT) family (SLC20), which use either Na(+) or H(+) to mediate
      inorganic phosphate (P(i)) symport. The mammalian PiT paralogs PiT1 and PiT2 are
      Na(+)-dependent P(i) (NaP(i)) transporters and are exploited by a group of
      retroviruses for cell entry. Human PiT1 and PiT2 were characterized by expression
      in Xenopus laevis oocytes with (32)P(i) as a traceable P(i) source. For PiT1, the
      Michaelis-Menten constant for P(i) was determined as 322.5 +/- 124.5 microM. PiT2
      was analyzed for the first time and showed positive cooperativity in P(i) uptake
      with a half-maximal activity constant for P(i) of 163.5 +/- 39.8 microM. PiT1-
      and PiT2-mediated Na(+)-dependent P(i) uptake functions were not significantly
      affected by acidic and alkaline pH and displayed similar Na(+) dependency
      patterns. However, only PiT2 was capable of Na(+)-independent P(i) transport at
      acidic pH. Study of the impact of divalent cations Ca(2+) and Mg(2+) revealed
      that Ca(2+) was important, but not critical, for NaP(i) transport function of PiT
      proteins. To gain insight into the NaP(i) cotransport function, we analyzed PiT2
      and a PiT2 P(i) transport knockout mutant using (22)Na(+) as a traceable Na(+)
      source. Na(+) was transported by PiT2 even without P(i) in the uptake medium and
      also when P(i) transport function was knocked out. This is the first time
      decoupling of P(i) from Na(+) transport has been demonstrated for a PiT family
      member. Moreover, the results imply that putative transmembrane amino acids E(55)
      and E(575) are responsible for linking P(i) import to Na(+) transport in PiT2.

PMID- 16790505
TI  - Atypical HUS and complement dysregulation.

PMID- 16790507
TI  - Involvements of Rho-kinase and TGF-beta pathways in aldosterone-induced renal
      injury.
AB  - Recent studies have suggested a role for aldosterone in the pathogenesis of renal
      injury. This study investigated the potential contributions of Rho-kinase and TGF
      beta pathways to aldosterone-induced renal injury. Rats were uninephrectomized
      and then treated for 5 wk with 1% NaCl in a drinking solution and one of the
      following: Vehicle (2% ethanol, subcutaneously; n = 9); aldosterone (0.75
      microg/h, subcutaneously; n = 9); or aldosterone + fasudil, a specific Rho-kinase
      inhibitor (10 mg/kg per d, subcutaneously; n = 8). Phosphorylation of myosin
      phosphate target subunit-1 (MYPT1) and Smad2/3 in renal cortical tissue was
      measured by Western blotting with anti-phospho MYPT1 and Smad2/3 antibodies,
      respectively. Rats that received aldosterone infusion exhibited hypertension and
      severe renal injury characterized by proteinuria, glomerular sclerosis, and
      tubulointerstitial fibrosis with increases in alpha-smooth muscle actin staining
      and numbers of monocytes/macrophages in the interstitium. Renal cortical mRNA
      levels of types I and III collagen, TGF-beta, connective tissue growth factor,
      and monocyte chemoattractant protein-1 as well as Smad2/3 phosphorylation were
      significantly increased in rats that received aldosterone infusion. All of these
      changes were associated with an increase in renal tissue MYPT1 phosphorylation.
      Treatment with fasudil did not alter BP but significantly ameliorated proteinuria
      and renal injury in rats that received aldosterone infusion. Furthermore, fasudil
      prevented MYPT1 phosphorylation and markedly decreased alpha-smooth muscle actin
      staining, numbers of monocytes/macrophages, mRNA levels of types I and III
      collagen, TGF-beta, connective tissue growth factor and monocyte chemoattractant
      protein-1, and Smad2/3 activity in renal cortical tissues. These results provide
      evidence, for the first time, that Rho-kinase is substantially involved in
      aldosterone-induced renal injury through activation of a TGF-beta-dependent
      pathway.

PMID- 16790508
TI  - Renal tubular dysgenesis, a not uncommon autosomal recessive disorder leading to
      oligohydramnios: Role of the Renin-Angiotensin system.
AB  - Renal tubular dysgenesis is a clinical disorder that is observed in fetuses and
      characterized by the absence or poor development of proximal tubules, early onset
      and persistent oligohydramnios that leads to the Potter sequence, and skull
      ossification defects. It may be acquired during fetal development or inherited as
      an autosomal recessive disease. It was shown recently that autosomal recessive
      renal tubular dysgenesis is genetically heterogeneous and linked to mutations in
      the genes that encode components of the renin-angiotensin system. This study
      analyzed the clinical expression of the disease in 29 fetus/neonates from 18
      unrelated families and evaluated changes in renal morphology and expression of
      the renin-angiotensin system. The disease was uniformly severe, with perinatal
      death in all cases as a result of persistent anuria and hypoxia related to
      pulmonary hypoplasia. Severe defects in proximal tubules were observed in all
      fetuses from 18 gestational weeks onward, and lesions also involved other tubular
      segments. They were associated with thickening of the renal arterial vasculature,
      from the arcuate to the afferent arteries. Renal renin expression was strikingly
      increased in 19 of 24 patients studied, from 13 families, whereas no renal renin
      was detected in four patients from three families. Angiotensinogen and
      angiotensin-converting enzyme were absent or present in only small amounts in the
      proximal tubule, in correlation with the severity of tubular abnormalities. No
      specific changes were detected in angiotensin II receptor expression. The
      severity and the early onset of the clinical and pathologic expression of the
      disease underline the major importance of this system in fetal kidney function
      and development in humans. The identification of the disease on the basis of
      precise histologic analysis and the research of the genetic defect now allow
      genetic counseling and early prenatal diagnosis.

PMID- 16790509
TI  - A hypomorphic mutation in the mouse laminin alpha5 gene causes polycystic kidney
      disease.
AB  - Extracellular matrix abnormalities have been found in both human and animal
      models of polycystic kidney disease (PKD). A new mouse PKD model has been
      produced through insertion of a PGKneo cassette in an intron of the gene that
      encodes laminin alpha5 (Lama5), a major tubular and glomerular basement membrane
      component that is important for glomerulogenesis and ureteric bud branching.
      Lama5neo represents a hypomorphic allele as a result of aberrant splicing.
      Lama5neo/neo mice exhibit PKD, proteinuria, and death from renal failure by 4 wk
      of age. This contrasts with mice that totally lack Lama5, which die in utero with
      multiple developmental defects. At 2 d of age, Lama5neo/neo mice exhibited mild
      proteinuria and microscopic cystic transformation. By 2 wk, cysts were grossly
      apparent in cortex and medulla, involving both nephron and collecting duct
      segments. Tubular basement membranes seemed to form normally, and early cyst
      basement membranes showed normal ultrastructure but developed marked thickening
      as cysts enlarged. Overall, Lama5 protein levels were severely reduced as a
      result of mRNA frameshift caused by exon skipping. This was accompanied by
      aberrant accumulation of laminin-332 (alpha3beta3gamma2; formerly called laminin
      5) in some cysts, as also observed in human PKD. This constitutes the first
      evidence that a primary defect in an extracellular matrix component can cause
      PKD.

PMID- 16790510
TI  - Mild tubular damage induces calcium oxalate crystalluria in a model of subtle
      hyperoxaluria: Evidence that a second hit is necessary for renal lithogenesis.
AB  - Environment and diet have a major role in calcium nephrolithiasis by affecting
      urine saturation, but this is not enough to cause lithogenesis; the crystals must
      adhere to the tubular epithelium (TE), but it is hard to say how environment and
      nutrition may be involved in this step. The hypothesis that TE damage (known to
      enhance crystal attachment) is lithogenic in mild hyperoxaluria was tested. Mild
      hyperoxaluria was induced in male Wistar rats using ethylene glycol (EG; 0.5% in
      water) for 21 d, and TE damage was induced by intraperitoneal administration of
      hexachloro-1:3-butadiene (HCBD; an industrial nephrotoxin) at 10, 25, and 50
      mg/kg body wt on days 7 and 14. These EG and HCBD concentrations were chosen to
      span from suboptimal to very low doses as far as effects on crystalluria and TE
      damage are concerned. Enzymuria, proteinuria, oxaluria, crystalluria, and renal
      pathology were investigated. All HCBD dosages induced crystalluria in mildly
      hyperoxaluric rats, but no intrarenal crystals were found. EG alone induced very
      mild hyperoxaluria but no damage to the renal tubule observable on transmission
      electron microscopy, and it did not cause crystalluria or intrarenal crystals.
      HCBD with the concomitant administration of EG caused apoptosis of the TE at the
      two highest dosages after the second injection. Apoptosis did not correlate with
      crystalluria. A TE toxin is needed for crystallogenesis to occur in borderline
      metabolic conditions. It may take more than just a metabolic predisposition for
      calcium nephrolithiasis to occur, and the second hit could come from an
      environmental pollutant such as HCBD.

PMID- 16790511
TI  - International comparison of the relationship of chronic kidney disease prevalence
      and ESRD risk.
AB  - ESRD incidence is much lower in Europe compared with the United States. This
      study investigated whether this reflects a difference in the prevalence of
      earlier stages of chronic kidney disease (CKD) or other mechanisms. CKD
      prevalence in Norway was estimated from the population-based Health Survey of
      Nord-Trondelag County (HUNT II), which included 65,181 adults in 1995 through
      1997 (participation rate 70.4%). Data were analyzed using the same methods as two
      US National Health and Nutrition Examination Surveys in 1988 through 1994 (n =
      15,488) and 1999 through 2000 (n = 4101). The primary analysis used gender
      specific cutoffs in estimating persistent albuminuria for CKD stages 1 and 2.
      ESRD rates and other relevant data were extracted from national registries. Total
      CKD prevalence in Norway was 10.2% (SE 0.5): CKD stage 1 (GFR >90 ml/min per 1.73
      m2 and albuminuria), 2.7% (SE 0.3); stage 2 (GFR 60 to 89 ml/min per 1.73 m2 and
      albuminuria), 3.2% (SE 0.4); stage 3 (GFR 30 to 59 ml/min per 1.73 m2), 4.2% (SE
      0.1); and stage 4 (GFR 15 to 29 ml/min per 1.73 m2), 0.2% (SE 0.01). This closely
      approximates reported US CKD prevalence (11.0% in 1988 through 1994 and 11.7% in
      1999 through 2000). The relative risk for progression from CKD stages 3 or 4 to
      ESRD in US white patients compared with Norwegian patients was 2.5. This was only
      modestly modified by adjustment for age, gender, and diabetes. Age and GFR at
      start of dialysis were similar, hypertension and cardiovascular mortality in the
      populations were comparable, but US white patients were referred later to a
      nephrologist and had higher prevalence of obesity and diabetes. In conclusion,
      CKD prevalence in Norway was similar to that in the United States, suggesting
      that lower progression to ESRD rather than a smaller pool of individuals at risk
      accounts for the lower incidence of ESRD in Norway.

PMID- 16790512
TI  - Intraluminal ATP concentrations in rat renal tubules.
AB  - It is becoming increasingly recognized that stimulation of apical P2 receptors
      can influence solute transport in the nephron, but, to date, no information is
      available on endogenous intraluminal nucleotide concentrations in vivo. This
      study measured intraluminal ATP concentrations in the renal tubules of
      anesthetized rats. Proximal tubular concentrations were found to be in the range
      of 100 to 300 nmol/L, with no significant variation along the S2 segment, whereas
      concentrations in the early distal tubule were markedly lower. Using collections
      of varying duration, the half-life of ATP in collected proximal tubular fluid was
      found to be 3.4 min, indicating significant breakdown by soluble nucleotidases.
      For assessment of whether proximal tubular ATP was filtered or secreted,
      experiments were performed in Munich-Wistar rats. The ATP concentration in
      midproximal tubules (142 +/- 23 nmol/L) was more than four-fold higher than in
      Bowman's space (32 +/- 7 nmol/L; P < 0.001), whereas fractional water
      reabsorption between the two sites was modest. In experiments that were designed
      to determine the effects of (patho)physiologic disturbances on intraluminal ATP,
      rats were either volume expanded or subjected to hypotensive hemorrhage. Neither
      maneuver affected proximal tubular luminal ATP concentrations significantly;
      rapid degradation of secreted ATP by ecto- and soluble nucleotidases is a
      possible explanation. It is concluded that the proximal tubule secretes ATP into
      the lumen, where it may have an autocrine/paracrine regulatory role.

PMID- 16790513
TI  - Transplanted mesenchymal stem cells accelerate glomerular healing in experimental
      glomerulonephritis.
AB  - Bone marrow-derived cells contribute to glomerular cell turnover and repair, but
      the cell types involved are unknown. Whether rat mesenchymal stem cells (MSC) can
      accelerate recovery from damage in rat mesangioproliferative anti-Thy1.1
      glomerulonephritis was studied. After injection into the left renal artery on day
      2 after disease induction, fluorescently labeled MSC were detected in 20 to 50%
      of glomeruli and rare intrarenal vessels but not in the tubulointerstitium, in
      contralateral kidneys, or in medium controls. In control experiments, injected
      mesangial cells were detected less frequently in glomeruli in comparison with
      injected MSC. In nephritic outbred Wistar rats, MSC injection led to an
      approximately 50% reduction of mesangiolysis on days 4 and 6 after disease
      induction, accompanied by three- to four-fold higher intraglomerular cell
      proliferation on day 4 and more rapid mesangial reconstitution as detected by
      alpha-smooth muscle actin expression. Injection of MSC into tail veins or intra
      arterial injection of mesangial cells instead of MSC failed to reproduce any of
      these findings. In inbred Lewis rats, anti-Thy1.1 nephritis followed an
      aggravated course with transient acute renal failure. Acute renal failure was
      ameliorated by MSC injection into the left renal artery on day 2 after disease
      induction. Again, MSC led to more rapid recovery from mesangiolysis, increased
      glomerular cell proliferation, and reduction of proteinuria by 28%. Double
      immunostaining of 5-bromo-2'-deoxyuridine-labeled MSC for endothelial, mesangial,
      or monocyte/macrophage antigens showed that 85 to 95% of MSC that localized in
      glomeruli on day 6 failed to express these markers. In vitro, MSC secreted high
      amounts of vascular endothelial growth factor and TGF-beta1 but not PDGF-BB. In
      conclusion, even low numbers of MSC can markedly accelerate glomerular recovery
      from mesangiolytic damage possibly related to paracrine growth factor release and
      not to differentiation into resident glomerular cell types or
      monocytes/macrophages.

PMID- 16790514
TI  - Angiotensin type 1 receptor blocker restores podocyte potential to promote
      glomerular endothelial cell growth.
AB  - Both podocytes and glomerular endothelial cells (GEN) are postulated to play
      important roles in the progression and potential regression of
      glomerulosclerosis. Inhibition of angiotensin is crucial in treatment of chronic
      kidney disease, presumably via effects on BP and extracellular matrix. This study
      aimed to investigate how angiotensin inhibition altered the interactions between
      podocytes and GEN. The effects of supernatants from primary cultured mouse
      podocytes, before or after sublethal injury by puromycin aminonucleoside, in the
      presence or absence of angiotensin type 1 receptor blocker (ARB), on GEN
      sprouting and growth were assessed. Supernatant from normal podocytes
      significantly increased GEN sprouting, whereas puromycin aminonucleoside-injured
      podocyte supernatant decreased these GEN responses. These effects were linked to
      decreased vascular endothelial growth factor A (VEGF-A) and angiopoietin-1 (Ang
      1) protein from injured podocytes. This downregulation of VEGF-A and Ang-1
      protein was reversed when injured podocytes were treated with ARB. Inhibition of
      VEGF-A or Ang-1 prevented this restored response by ARB. Activation of
      intracellular kinases (p38, extracellular signal-regulated kinase, and AKT) was
      suppressed in GEN that were treated with medium from injured podocytes but
      restored by medium from ARB-treated injured podocytes. Therefore, injured
      podocytes are ineffective in promoting GEN sprouting, and this effect is reversed
      by ARB treatment of the injured podocyte. These data support the idea that ARB
      effects on podocytes may mediate capillary remodeling in vivo.

PMID- 16790515
TI  - Maternal serum alpha-fetoprotein level during pregnancy and isolated
      cryptorchidism in male offspring.
AB  - Cryptorchidism is thought to result from a disruption of the androgen-estrogen
      balance in utero. Alpha-fetoprotein (AFP) interacts with and may modulate fetal
      responses to estrogens. Using a cohort of boys born to women participating in a
      Danish maternal serum AFP screening program between 1980 and 1994, the authors
      explored whether AFP levels (as reflected by maternal serum AFP levels in
      gestational weeks 14-22) were associated with the risk of isolated cryptorchidism
      in male offspring. Cryptorchidism diagnoses and covariate information were
      obtained from Denmark's national health registries. Risk ratios for
      cryptorchidism by maternal serum AFP multiples of the median were estimated by
      use of log-linear binomial regression. Of 25,418 boys, 663 (2.6%) were diagnosed
      with cryptorchidism. After adjustment for confounders, boys with maternal serum
      AFP levels greater than or equal to 2.5 times the median had a 63% (95%
      confidence interval: -2, 172) greater risk of cryptorchidism than did boys with
      maternal serum AFP levels within 25% of the median. High fetal AFP levels may
      contribute directly to events producing cryptorchidism; alternatively, elevated
      maternal serum AFP levels may reflect placental dysfunction, some aspect of which
      contributes to cryptorchidism.

PMID- 16790516
TI  - Phase II trial of temozolomide and cisplatin followed by whole brain radiotherapy
      in non-small-cell lung cancer patients with brain metastases: a GLOT-GFPC study.
AB  - BACKGROUND: Brain metastases (BM) considerably worsen the prognosis of non-small
      cell lung cancer (NSCLC) patients. The usefulness and choice of chemotherapy
      remain uncertain in this indication since these patients are excluded from most
      clinical trials. We conducted a phase II study to determine the efficacy and
      tolerability of up-front chemotherapy with association of temozolomide and
      cisplatin in NSCLC patients with BM. PATIENTS AND METHODS: Fifty NSCLC patients
      with BM received temozolomide (200 mg/m(2)/day for 5 days every 28 days) and
      cisplatin (75 mg/m(2) at day 1 of each cycle), up to six cycles, followed by
      whole brain radiotherapy (WBRT). An evaluation was carried out every two cycles
      and after WBRT. WBRT was performed earlier in case of progressive disease at any
      time or stable disease after cycle 4. RESULTS: Eight objective responses were
      achieved (16%). Overall median survival was 5 months. Median time to progression
      was 2.3 months. Ten patients (20%) presented a grade 3/4 neutropenia and 11
      patients (22%) presented a grade 3/4 thrombopenia. CONCLUSION: This study
      demonstrates a lack of efficacy of up-front chemotherapy with association of
      temozolomide and cisplatin in these patients. Nevertheless, it supports the
      feasibility of chemotherapy before brain radiotherapy in NSCLC patients with BM.

PMID- 16790517
TI  - Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in
      advanced non-nasopharyngeal head and neck cancer. An efficacy and cost analysis
      randomized study conducted by the Hellenic Cooperative Oncology Group.
AB  - BACKGROUND: The prognosis of patients with recurrent and/or metastatic head and
      neck cancer (HNC) is poor. Median survival of these patients following
      chemotherapy is in the range of 6 to 9 months. In the present randomized phase
      III trial we compared two new combinations containing new drugs with proven
      activity in phase II studies with patients with HNC. PATIENTS AND METHODS: From
      November 1999 until November 2004, 166 eligible patients with HNC were enrolled
      in the study. They were treated with paclitaxel 175 mg/m(2) on day 1 and
      gemcitabine 1000 mg/m(2) on days 1 and 8 every 3 weeks (group A, 85 patients) or
      with paclitaxel, as in group A, and pegylated liposomal doxorubicin 40 mg/m(2) on
      day 1 every 4 weeks (group B, 81 patients). RESULTS: There was no significant
      difference in response rate (20% versus 29%, P = 0.21), time to disease
      progression (median; 4.4 months versus 6.0 months, P = 0.09) and survival
      (median; 8.6 months versus 11.05 months, P = 0.25). Both regimens were generally
      well tolerated. The most frequently reported side effect, apart from alopecia,
      was neutropenia. Overall, there was no significant difference in severe toxicity
      between the two treatment arms. CONCLUSIONS: The present study could not
      demonstrate a survival benefit with either regimen. Both treatments were well
      tolerated. Randomized studies comparing each of the two regimens with standard
      chemotherapy are warranted.

PMID- 16790518
TI  - Extramedullary disease and targeted therapies for hematological malignancies--is
      the association real?
AB  - During the past years targeted therapies have gained a major role in the
      treatment of cancer patients, including those with hematological malignancies.
      Extramedullary involvement is a rare manifestation of acute and chronic leukemias
      and of multiple myeloma. Nevertheless, with the expanding use of targeted
      treatments there is an impression that the incidence of extramedullary relapses
      is increasing. We reviewed the reports on this phenomenon in patients treated
      with all-trans-retinoic acid and arsenic trioxide for acute promyelocytic
      leukemia, thalidomide and bortezomib for multiple myeloma and imatinib for
      chronic myeloid leukemia. The pathogenetic mechanisms suggested are: life
      prolongation by these treatments allowing for disease progression arising from
      dormant cells; poor penetration of the drugs to sanctuary sites like the central
      nervous system; the requirement of some of these drugs, especially thalidomide,
      for the marrow microenvironment to exert their action; and finally, a possible
      active role for some of the drugs, like all-trans-retinoic acid. Since the use of
      these targeted therapies is expanding we should be aware of this association.

PMID- 16790519
TI  - Bevacizumab is active in malignant effusion.

PMID- 16790521
TI  - Role of platinum-based radio-chemotherapy for locally advanced non-small-cell
      lung cancer: possible influence of type of platinum on survival data.

PMID- 16790520
TI  - Adjuvant systemic treatment of early breast cancer: the NORA study.
AB  - BACKGROUND: Despite recommendations contained in international guidelines,
      factors such as the type of oncology centre, geographic distribution and the
      introduction of scientific advances into clinical practice can influence the
      choice of recommended treatment for early breast cancer. The NORA study is a
      prospective, longitudinal cohort study aimed at investigating tumour
      characteristics, treatment modalities, and other factors that influence
      therapeutic choices in early breast cancer patients who have undergone mastectomy
      or breast-conserving surgery (BCS). PATIENTS AND METHODS: From January 2000 to
      early 2004, we collected data on methods of cancer diagnosis, type of surgery and
      adjuvant medical treatment administered to the first 10 consecutive patients
      treated in 2000-2002 and the first 20 consecutive patients in 2003 and 2004 at 71
      oncology centres in Italy, with the approval of the ethical committee at each
      centre. RESULTS: Approximately one-quarter of the cases (26.5%) were detected
      through screening programmes. BCS was performed in 63.7% and sentinel node biopsy
      (SNB) occurred in 11.1% of the patients. Of the 3515 total cases, 56.5% were node
      negative. Grade 2 cancers comprised 51.3%, and 66.2% were hormone-receptor
      positive (ER+/PgR+). Chemotherapy (CHT) followed by hormone therapy (HT) was the
      most prescribed treatment (48.5%). CHT was mainly anthracycline-based (52.9%) and
      most patients received tamoxifen alone (77.7%) or after CHT (85.2%). For node
      negative patients, HR+ and menopause status are the factors influencing the
      choice to add HT after CHT; patients with HR+ and pT4 tumours are more likely to
      receive HT instead of CHT. In node-positive patients, the addition of HT is
      influenced by HR+ status, the opportunity to have HT instead of CHT, and
      menopause. CONCLUSIONS: NORA is the first large cohort study to describe the
      factors that influence therapeutic choices in early breast cancer. Understanding
      these findings can help physicians in daily clinical practice.

PMID- 16790522
TI  - Trigger for group A streptococcal M1T1 invasive disease.
AB  - The globally disseminated Streptococcus pyogenes M1T1 clone causes a number of
      highly invasive human diseases. The transition from local to systemic infection
      occurs by an unknown mechanism; however invasive M1T1 clinical isolates are known
      to express significantly less cysteine protease SpeB than M1T1 isolates from
      local infections. Here, we show that in comparison to the M1T1 strain 5448, the
      isogenic mutant delta speB accumulated 75-fold more human plasmin activity on the
      bacterial surface following incubation in human plasma. Human plasminogen was an
      absolute requirement for M1T1 strain 5448 virulence following subcutaneous (s.c.)
      infection of humanized plasminogen transgenic mice. S. pyogenes M1T1 isolates
      from the blood of infected humanized plasminogen transgenic mice expressed
      reduced levels of SpeB in comparison with the parental 5448 used as inoculum. We
      propose that the human plasminogen system plays a critical role in group A
      streptococcal M1T1 systemic disease initiation. SpeB is required for S. pyogenes
      M1T1 survival at the site of local infection, however, SpeB also disrupts the
      interaction of S. pyogenes M1T1 with the human plasminogen activation system.
      Loss of SpeB activity in a subpopulation of S. pyogenes M1T1 at the site of
      infection results in accumulation of surface plasmin activity thus triggering
      systemic spread.

PMID- 16790523
TI  - Integrin alphaVbeta3 contains a receptor site for resveratrol.
AB  - Resveratrol is a naturally occurring polyphenol, which causes apoptosis in
      cultured cancer cells. We describe a cell surface resveratrol receptor on the
      extracellular domain of hetero-dimeric alphaVbeta3 integrin in MCF-7 human breast
      cancer cells. This receptor is linked to induction by resveratrol of
      extracellular-regulated kinases 1 and 2 (ERK1/2)- and serine-15-p53-dependent
      phosphorylation leading to apoptosis. The integrin receptor is near the Arg-Gly
      Asp (RGD) recognition site on the integrin; an integrin-binding RGD peptide
      inhibits induction by resveratrol of ERK1/2- and p53-dependent apoptosis.
      Antibody (Ab) to integrin alphaVbeta3, but not to alphaVbeta5, inhibits
      activation by resveratrol of ERK1/2 and p53 and consequent apoptosis in estrogen
      receptor-alpha (ERalpha) positive MCF-7, and ERalpha-negative MDA-MB231 cells.
      Resveratrol is displaced from the purified integrin by an RGD, but not RGE,
      peptide, and by alphaVbeta3 integrin-specific Ab. Resveratrol action is blocked
      by siRNAbeta3, but not by siRNAalphaV. [14C]-Resveratrol binds to commercially
      purified integrin alphaVbeta3 and to alphaVbeta3 prepared from MCF-7 cells;
      binding of [14C]-resveratrol to the beta3, but not to the alphaV monomer, is
      displaced by unlabeled resveratrol. In conclusion, binding of resveratrol to
      integrin alphaVbeta3, principally to the beta3 monomer, is essential for
      transduction of the stilbene signal into p53-dependent apoptosis of breast cancer
      cells.

PMID- 16790524
TI  - Simvastatin promotes angiogenesis and prevents microvascular remodeling in
      chronic renal ischemia.
AB  - We tested the hypothesis that statins would decrease renal injury in renal artery
      stenosis (RAS) by restoring angiogenesis and attenuating intrarenal microvascular
      (IMV) remodeling. Single-kidney hemodynamics and function were quantified using
      electron-beam-computed tomography (CT) in normocholesterolemic pigs after 12 wk
      of experimental RAS, RAS supplemented with simvastatin (RAS+simvastatin), and
      normal controls. Renal circulation was also studied in vivo using angiography and
      ex vivo using a unique 3D micro-CT imaging technique. Angiogenic and remodeling
      pathways were subsequently explored in renal tissue. Blood pressure and the
      degree of stenosis were similarly increased in RAS groups. Simvastatin in RAS
      enhanced both intrarenal angiogenesis and peri-stenosis arteriogenesis and
      increased the expression of angiogenic growth factors and hypoxia-inducible
      factor-1alpha. Furthermore, simvastatin decreased tissue-transglutaminase
      expression and IMV inward remodeling, restored IMV endothelial function,
      decreased fibrogenic activity, and improved renal function. Chronic simvastatin
      supplementation promoted angiogenesis in vivo, decreased ischemia-induced IMV
      remodeling, and improved IMV function in the stenotic kidney, independent of
      lipid lowering. These novel renoprotective effects suggest a role for simvastatin
      in preserving the ischemic kidney in chronic RAS.

PMID- 16790525
TI  - A negative feedback loop of transcription factors that controls stem cell
      pluripotency and self-renewal.
AB  - Embryonic stem (ES) cells possess the ability to renew themselves while
      maintaining the capacity to differentiate into virtually all cell types of the
      body. Current evidence suggests that ES cells maintain their pluripotent state by
      expressing a battery of transcription factors including Oct4 and Nanog. However,
      little is known about how ES cells maintain the expression of these pluripotent
      factors in ES cells. Here we present evidence that Oct4, Nanog, and FoxD3 form a
      negative feedback loop to maintain their expression in pluripotent ES cells.
      First, Oct4 maintains Nanog activity by directly activating its promoter at sub
      steady-state concentration but repressing it at or above steady-state levels. On
      the other hand, FoxD3 behaves as a positive activator of Nanog to counter the
      repressive effect of Oct4. The expression of Oct4 is activated by FoxD3 and Nanog
      but repressed by Oct4 itself, thus, exerting an important negative feedback loop
      to limit its own activity. Indeed, overexpression of either FoxD3 or Nanog in ES
      cells failed to increase the concentration of Oct4 beyond the steady-state
      concentration, whereas knocking down either FoxD3 or Nanog reduces the expression
      of Oct4 in ES cells. Finally, overexpression of Oct4 or Nanog failed to
      compensate the loss of Nanog or Oct4, respectively, suggesting that both are
      required for ES self-renewal and pluripotency. Our results suggest the FoxD3
      Nanog-Oct4 loop anchors an interdependent network of transcription factors that
      regulate stem cell pluripotency.

PMID- 16790526
TI  - Antagonism of platelet-derived growth factor by perivascular gene transfer
      attenuates adventitial cell migration after vascular injury: new tricks for old
      dogs?
AB  - Migration of adventitial fibroblasts contributes to vascular remodeling after
      angioplasty. This study has used perivascular gene transfer of a truncated
      platelet-derived growth factor PDGF receptor (PDGFXR) to investigate whether
      antagonism of PDGF signaling alters adventitial cell migration after balloon
      injury in rat carotid arteries. Adenoviruses coordinating expression of beta
      galactosidase (LacZ) and PDGFXR or LacZ and green fluorescent protein (GFP) were
      applied to the perivascular surface of arteries and balloon injury performed 4
      days later. Vessels were excised at 3, 7, and 14 days to determine morphology and
      gene expression. Uninjured arteries only expressed LacZ positive cells in the
      adventitial compartment; however, after injury in LacZ and GFP transfected
      arteries, LacZ positive cells contributed to the population of cells within the
      media and neointima at 7-14 days. Overexpression of PDGFXR and LacZ resulted in a
      significant reduction in the number of LacZ labeled cells in the neointima after
      vascular injury, concomitant with reduced remodeling, collagen content,
      expression of matrix metalloproteinase-2, and increased levels of tissue
      inhibitors of metalloproteinase-1 and -2. We provide evidence that perivascular
      antagonism of PDGF attenuates remodeling and contribution of adventitial
      fibroblasts to neointima formation after balloon angioplasty. Perivascular gene
      transfer may represent a therapeutic strategy to reduce the incidence of
      restenosis.

PMID- 16790527
TI  - Mitochondrial damage due to SOD1 deficiency in SH-SY5Y neuroblastoma cells: a
      rationale for the redundancy of SOD1.
AB  - Superoxide dismutases (SODs) represent the first line of defense against
      oxidative stress, which is considered an essential factor in several
      neurodegenerative diseases and aging. We investigated the role of the copper,zinc
      superoxide dismutase (SOD1) in the maintenance of intracellular redox homeostasis
      by analyzing the early effects of SOD1 down-regulation in SH-SY5Y neuroblastoma
      cells. Through the use of small interference RNA, SOD1 was efficiently down
      regulated at 48 h after transfection without any significant effect on cell
      viability. The steady-state concentration of superoxide was significantly
      increased after 12 h, when SOD1 was only slightly decreased, and progressively
      returned to values close to those observed in control cells. The superoxide
      increase was buffered by the enhanced levels of antioxidant glutathione (GSH);
      however, GSH increase was not sufficient to avoid damage to proteins in terms of
      carbonyls. GSH-depleting agents, such as BSO or diamide, further increased
      protein damage and committed SOD1 deficient cells to death, confirming the
      pivotal role played by this antioxidant. Although SOD1 declined mostly in the
      cytosolic compartment, mitochondria were significantly affected with impairment
      of the mitochondrial transmembrane potential and a decrease in ATP production.
      Together with these effects carbonylation of mitochondrial proteins was detected
      and in particular a consistent carbonylation and decrease of the antiapoptotic
      protein Bcl-2. These conditions induced a high susceptibility of SOD1-depleted
      cells to treatment with the mitochondrial reactive oxygen species producing agent
      rotenone. Overall, the results demonstrate that loss of SOD1 leads to severe
      damage of mitochondria, suggesting an important biological role for this enzyme
      in the preservation of mitochondrial homeostasis.

PMID- 16790528
TI  - SAP155 Binds to ceramide-responsive RNA cis-element 1 and regulates the
      alternative 5' splice site selection of Bcl-x pre-mRNA.
AB  - Two splice variants are derived from the BCL-x gene, proapoptotic Bcl-x(s) and
      antiapoptotic Bcl-x(L), via alternative 5' splice site selection. In previous
      studies, our laboratory identified an RNA cis-element within exon 2 of Bcl-x pre
      mRNA that is a ceramide responsive termed CRCE 1. In this study, mass
      spectrometric analysis identified the splicing factor SAP155, as an RNA trans
      acting factor binding to the purine-rich CRCE 1. The interaction of SAP155 with
      CRCE 1 was confirmed by the addition of an anti-SAP155 antibody (Ab) to EMSA
      decreasing the mobility of a protein:CRCE 1 complex (SuperShift). Furthermore,
      the down-regulation of SAP155 in A549 cells by RNA interference (RNAi) technology
      resulted in the loss of a 155 kDa protein complexed with CRCE 1. Moreover, this
      down-regulation of SAP155 induced an increase in the Bcl-x(s) with a concomitant
      decrease in the Bcl-x(L) splice variants and immunoreactive protein levels,
      thereby decreasing the Bcl-x(L)/Bcl-x(s) ratio. Specific down-regulation of
      SAP155 also inhibited the ability of exogenous ceramide treatment to further
      induce the activation of the Bcl-x(s) 5' splice site. Additionally, the specific
      down-regulation of SAP155 sensitized cells to undergo apoptosis in response to
      daunorubicin in a manner similar to ceramide. Therefore, we have identified
      SAP155 as an RNA trans-acting factor that binds to CRCE 1, functions to regulate
      the alternative 5' splice site selection of Bcl-x pre-mRNA, and is required for
      ceramide to induce the activation of the Bcl-x(s) 5' splice site. Furthermore, we
      have demonstrated that activation of the Bcl-x(s) 5' splice site can increase the
      effectiveness of chemotherapeutic drug treatment, thus establishing a role for
      the alternative splicing mechanism of Bcl-x in chemotherapeutic sensitivity.

PMID- 16790529
TI  - Connective tissue growth factor/CCN2 stimulates actin disassembly through
      Akt/protein kinase B-mediated phosphorylation and cytoplasmic translocation of
      p27(Kip-1).
AB  - Connective tissue growth factor (CTGF/CCN2) is a 38-kDa secreted protein, a
      prototypic member of the CCN family, which is up-regulated in many diseases,
      including atherosclerosis, pulmonary fibrosis, and diabetic nephropathy. We
      previously showed that CTGF can cause actin disassembly with concurrent down
      regulation of the small GTPase Rho A and proposed an integrated signaling network
      connecting focal adhesion dissolution and actin disassembly with cell
      polarization and migration. Here, we further delineate the role of CTGF in cell
      migration and actin disassembly in human mesangial cells, a primary target in the
      development of renal glomerulosclerosis. The functional response of mesangial
      cells to treatment with CTGF was associated with the phosphorylation of
      Akt/protein kinase B (PKB) and resultant phosphorylation of a number of Akt/PKB
      substrates. Two of these substrates were identified as FKHR and p27(Kip-1). CTGF
      stimulated the phosphorylation and cytoplasmic translocation of p27(Kip-1) on
      serine 10. Addition of the PI-3 kinase inhibitor LY294002 abrogated this
      response; moreover, addition of the Akt/PKB inhibitor interleukin (IL)-6
      hydroxymethyl-chiro-inositol-2(R)-2-methyl-3-O-octadecylcarbonate prevented
      p27(Kip-1) phosphorylation in response to CTGF. Immunocytochemistry revealed that
      serine 10 phosphorylated p27(Kip-1) colocalized with the ends of actin filaments
      in cells treated with CTGF. Further investigation of other Akt/PKB sites on
      p27(Kip-1), revealed that phosphorylation on threonine 157 was necessary for CTGF
      mediated p27(Kip-1) cytoplasmic localization; mutation of the threonine 157 site
      prevented cytoplasmic localization, protected against actin disassembly and
      inhibited cell migration. CTGF also stimulated an increased association between
      Rho A and p27(Kip-1). Interestingly, this resulted in an increase in
      phosphorylation of LIM kinase and subsequent phosphorylation of cofilin,
      suggesting that CTGF mediated p27(Kip-1) activation results in uncoupling of the
      Rho A/LIM kinase/cofilin pathway. Confirming the central role of Akt/PKB, CTGF
      stimulated actin depolymerization only in wild-type mouse embryonic fibroblasts
      (MEFs) compared to Akt-1/3 (PKB alpha/gamma) knockout MEFs. These data reveal
      important mechanistic insights into how CTGF may contribute to mesangial cell
      dysfunction in the diabetic milieu and sheds new light on the proposed role of
      p27(Kip-1) as a mediator of actin rearrangement.

PMID- 16790530
TI  - The novel beta-defensin DEFB123 prevents lipopolysaccharide-mediated effects in
      vitro and in vivo.
AB  - Defensins are a family of secreted antimicrobial peptides proposed to directly
      interfere with bacterial membranes. Here we show a functional analysis of the
      novel beta-defensin DEFB123. A peptide comprising the beta-defensin core region
      was synthesized and used for our analysis. Like other beta-defensins, DEFB123
      exerted antimicrobial activity against a broad spectrum of Gram-positive and Gram
      negative bacteria, which was assessed by microbroth dilution assay and radial
      diffusion zone assay. In addition, the peptide showed lipopolysaccharide (LPS)
      binding activity in a Limulus amoebocyte lysate (LAL) assay. Moreover, DEFB123
      prevented LPS-induced tumor necrosis factor (TNF)-alpha secretion in a murine
      monocyte cell line (RAW264.7). Accordingly, DEFB123 abolished LPS-mediated MAPK
      induction in these cells. Protection against LPS-mediated effects was then
      investigated in a murine model of acute sepsis. Our experiments show that
      synthetic beta-defensin DEFB123 prevents LPS-induced mortality in C57BL/6 mice in
      a therapeutic approach. We propose that the physiological role of beta-defensins
      may include interference with LPS-action on macrophages, a function formerly
      thought to be restricted to the family of cathelicidins, a structurally unrelated
      group of antimicrobial peptides.

PMID- 16790531
TI  - How effective are rapid access chest pain clinics? Prognosis of incident angina
      and non-cardiac chest pain in 8762 consecutive patients.
AB  - OBJECTIVE: To determine whether rapid access chest pain clinics are clinically
      effective by comparison of coronary event rates in patients diagnosed with angina
      with rates in patients diagnosed with non-cardiac chest pain and the general
      population. DESIGN: Multicentre cohort study of consecutive patients with chest
      pain attending the rapid access chest pain clinics (RACPCs) of six hospitals in
      England. PARTICIPANTS: 8762 patients diagnosed with either non-cardiac chest pain
      (n = 6396) or incident angina without prior myocardial infarction (n = 2366) at
      first cardiological assessment, followed up for a median of 2.57 (interquartile
      range 1.96-4.15) years. MAIN OUTCOME MEASURES: Primary end point--death due to
      coronary heart disease (International Classification of Diseases (ICD)10 I20-I25)
      or acute coronary syndrome (non-fatal myocardial infarction (ICD10 I21-I23),
      hospital admission with unstable angina (I24.0, I24.8, I24.9)). Secondary end
      points--all-cause mortality (ICD I20), cardiovascular death (ICD10 I00-I99), or
      non-fatal myocardial infarction or non-fatal stroke (I60-I69). RESULTS: The
      cumulative probability of the primary end point in patients diagnosed with angina
      was 16.52% (95% confidence interval (CI) 14.88% to 18.32%) after 3 years compared
      with 2.73% (95% CI 2.29% to 3.25%) in patients with non-cardiac chest pain.
      Coronary standardised mortality ratios for men and women with angina aged <65
      years were 3.52 (95% CI 1.98 to 5.07) and 4.39 (95% CI 1.14 to 7.64). Of the 599
      patients who had the primary end point, 194 (32.4%) had been diagnosed with non
      cardiac chest pain. These patients were younger, less likely to have typical
      symptoms, more likely to be south Asian and more likely to have a normal resting
      electrocardiogram than patients with angina who had the primary end point.
      CONCLUSION: RACPCs are successful in identifying patients with incident angina
      who are at high coronary risk, but there is a need to reduce misdiagnosis and
      improve outcomes in patients diagnosed with non-cardiac chest pain who accounted
      for nearly one third of cardiac events during follow-up.

PMID- 16790532
TI  - HIV-1 viral envelope glycoprotein gp120 triggers an inflammatory response in
      cultured rat astrocytes and regulates the functional expression of P
      glycoprotein.
AB  - In this work, we examined the ability of gp120, a human immunodeficiency virus-1
      (HIV-1) viral envelope glycoprotein, to trigger the innate immune response in
      astrocytes, an HIV-1 brain cellular target, and we investigated the functional
      expression of the ATP-binding cassette membrane transporter P-glycoprotein (P-gp)
      in primary cultures of rat astrocytes treated with gp120 or cytokines [tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6].
      Standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium and d-mannitol
      uptake assays confirmed that HIV-1(96ZM651) gp120 treatment did not alter cell
      viability or membrane permeability. Semiquantitative reverse-transcriptase
      polymerase chain reaction analysis and enzyme-linked immunosorbent assay
      demonstrated increased TNF-alpha, IL-1beta, and IL-6 mRNA and protein expression
      in cultures treated with HIV-1(96ZM651) gp120, suggesting in vitro activation of
      immune responses. Cytokine secretion was detected when CXCR4 but not CCR5 was
      inhibited with a specific antibody, implying that cytokine secretion is primarily
      mediated via CCR5 in astrocytes triggered with HIV-1(96ZM651) gp120. P-gp protein
      expression was increased in astrocyte cultures exposed to TNF-alpha (2.9-fold) or
      IL-1beta (1.6-fold) but was decreased profoundly in the presence of IL-6 (8.9
      fold), suggesting that IL-6 is primarily involved in modulating P-gp expression.
      In parallel, after HIV-1(96ZM651) gp120 treatment, immunoblotting analysis showed
      a significant decrease in P-gp expression (4.7-fold). Furthermore, the
      accumulation of two P-gp substrates, digoxin and saquinavir (an HIV-1 protease
      inhibitor), was enhanced (1.5- to 1.8-fold) in HIV-1(96ZM651) gp120-treated
      astrocyte monolayers but was not altered by P-gp inhibitors [e.g., valspodar
      (PSC833) and elacridar (GF120918)], suggesting a loss of transport activity.
      Taken together, these data imply that HIV-1(96ZM651) gp120 or cytokine treatment
      modulate P-gp functional expression in astrocytes, which may lead to complex drug
      transporter interactions during HIV-1 encephalitis-associated immune responses.

PMID- 16790533
TI  - A potential role for cyclized quinones derived from dopamine, DOPA, and 3,4
      dihydroxyphenylacetic acid in proteasomal inhibition.
AB  - We examined the ability of oxidation products of dopamine, DOPA, and 3,4
      dihydroxyphenylacetic acid (DOPAC) to inhibit proteasomal activity. Dopamine,
      DOPA, and DOPAC underwent tyrosinase-catalyzed oxidation to generate aminochrome,
      dopachrome, and furanoquinone, respectively. In these studies, the oxidation of
      dopamine by tyrosinase generated product(s) that inhibited the proteasome, and
      proteasomal inhibition correlated with the presence of the UV-visible spectrum of
      aminochrome. The addition of superoxide dismutase and catalase did not prevent
      proteasomal inhibition. The addition of NADH and the quinone reductase
      NAD(P)H:quinone oxidoreductase 1 (NQO1) protected against aminochrome-induced
      proteasome inhibition. Although NQO1 protected against dopamine-induced
      proteasomal inhibition, the metabolism of aminochrome by NQO1 led to oxygen
      uptake because of the generation of a redox-labile cyclized hydroquinone, further
      demonstrating the lack of involvement of oxygen radicals in proteasomal
      inhibition. DOPA underwent tyrosinase-catalyzed oxidation to form dopachrome, and
      similar to aminochrome, proteasomal inhibition correlated with the presence of a
      dopachrome UV-visible spectrum. The inclusion of NQO1 did not protect against
      proteasomal inhibition induced by dopachrome. Oxidation of DOPAC by tyrosinase
      generated furanoquinone, which was a poor proteasome inhibitor. These studies
      demonstrate that oxidation products, including cyclized quinones derived from
      dopamine and related compounds, rather than oxygen radicals have the ability to
      inhibit the proteasome. They also suggest an important protective role for NQO1
      in protecting against dopamine-induced proteasomal inhibition. The ability of
      endogenous intermediates formed during dopaminergic metabolism to cause
      proteasomal inhibition provides a potential basis for the selectivity of
      dopaminergic neuron damage in Parkinson's disease.

PMID- 16790534
TI  - Chiropractic research equals osteopathic research?

PMID- 16790535
TI  - Maintaining competence and leadership in manual medicine.

PMID- 16790536
TI  - Suggestions and questions for osteopathic medical education.

PMID- 16790537
TI  - Future of osteopathic medicine depends on investing in graduate medical
      education.

PMID- 16790538
TI  - Osteopathic evaluation and manipulative treatment in reducing the morbidity of
      otitis media: a pilot study.
AB  - OBJECTIVE: To study the effects of osteopathic manipulative treatment in routine
      pediatric care for children with recurrent acute otitis media. STUDY DESIGN:
      Pilot cohort study with 1-year posttreatment follow-up. At follow-up, subjects'
      parents or legal guardians and their referring and/or family physicians were
      contacted to determine recurrence of otitis media since intervention. SUBJECTS: A
      referred and volunteer sample of pediatric patients ranging in age from 7 months
      to 35 months with a history of recurrent otitis media (N=8). INTERVENTION: For 3
      weeks, all subjects received weekly osteopathic structural examinations and
      osteopathic manipulative treatment. This intervention was performed concurrently
      with traditional medical management. RESULTS: Five (62.5%) subjects had no
      recurrence of symptoms. Of the three remaining subjects in this cohort, one had a
      bulging tympanic membrane, another had four episodes of otitis media, and the
      last underwent surgery after recurrence at 6 weeks posttreatment. Closer analysis
      of the posttreatment course of the last two subjects indicates that there may
      have been a clinically significant decrease in morbidity for a period of time
      after intervention. CONCLUSION: The present study indicates that osteopathic
      manipulative treatment may change the progression of recurrent otitis media, a
      finding that supports the need for additional research in this area.

PMID- 16790539
TI  - Recording the rate of the cranial rhythmic impulse.
AB  - The rate of the cranial rhythmic impulse can be obtained by both palpation and
      instrumentation. However, the literature has reported higher rates obtained by
      instrumentation compared with palpation. The cranial rhythmic impulse has been
      demonstrated to be synchronous with the Traube-Hering oscillation, measured in
      blood flow velocity. The current study demonstrates that physicians tend to
      palpate the cranial rhythmic impulse and Traube-Hering oscillation in a 1:2
      ratio. This finding provides an explanation for the difference between palpated
      and instrumentally recorded rates for the cranial rhythmic impulse.

PMID- 16790540
TI  - Does long-distance running cause osteoarthritis?
AB  - There is a dose-response relationship between physical activity and the reduced
      risk of some diseases (eg, cardiovascular disease, diabetes mellitus). At a
      certain "dose," however, the reduced risk of some diseases may be offset by an
      increased risk of injury and osteoarthritis. Osteoarthritis can be caused by
      trauma to, or overuse of, the joints. Sports injuries often occur as a result of
      dysfunctions in balance or the musculoskeletal system operating in nonneutral
      mechanics. It is unclear if long-distance running causes the knee and hip joints
      to deteriorate. The results of animal studies reveal a pattern of increased
      incidence of arthritis in these joints when there is a history of injury or use
      in atypical environments (eg, laboratory settings). Human studies show an
      increase in radiographic evidence of osteoarthritis in endurance sports athletes,
      but no related increase in symptoms reported. Although there are not currently
      enough data to give clear recommendations to long-distance runners, it appears
      that long-distance running does not increase the risk of osteoarthritis of the
      knees and hips for healthy people who have no other counterindications for this
      kind of physical activity. Long-distance running might even have a protective
      effect against joint degeneration. The authors recommend further study.

PMID- 16790541
TI  - Osteopathic manipulative treatment of a 27-year-old man after anterior cruciate
      ligament reconstruction.
AB  - Increasing instability of the knee developed in a 27-year-old man who had torn
      his anterior cruciate ligament (ACL) approximately 10 years prior to surgical
      intervention. After initial conservative treatment, including use of a functional
      brace for activity, the patient opted for surgical reconstruction with a patellar
      tendon graft. One of the authors conducted three preoperative examinations to
      assess the condition of the patient's musculoskeletal system. These manual
      examinations included findings of somatic dysfunction in the lumbo-pelvic region.
      In addition, there was extension of muscular tension from the injured left knee
      and ankle into the lower thorax and ribs 6 through 9. During the postoperative
      rehabilitation process, examination at regular intervals included documentation
      of somatic dysfunction and osteopathic manipulative treatment (OMT). Following
      ACL reconstruction and OMT, the patient showed increasingly stable mobility in
      the lumbopelvic region. Furthermore, episodic new dysfunctions readily resolved
      with OMT. The patient returned to his regular sports activities 6 months after
      surgery.

PMID- 16790543
TI  - Memantine: the next trend in academic performance enhancement?

PMID- 16790542
TI  - Competence levels in musculoskeletal medicine: comparison of osteopathic and
      allopathic medical graduates.
AB  - BACKGROUND: Consistent with osteopathic principles and practice, the nation's
      colleges of osteopathic medicine (COMs) have emphasized the significance of the
      musculoskeletal system to the practice of medicine. The authors hypothesized that
      graduating COM students would, therefore, demonstrate superior knowledge and
      competence in musculoskeletal medicine when compared with graduates of allopathic
      medical schools. METHODS: The authors asked graduating COM students to complete a
      standardized and previously validated 25-question basic competency examination on
      musculoskeletal medicine in short-answer format. Originally developed and
      validated in the late 1990s, the examination was distributed to allopathic
      medical residents at the beginning of their residencies. The authors compare
      their results with those reported by Freedman and Bernstein for allopathic
      residents. RESULTS: When the minimum passing level as determined by orthopedic
      program directors was applied to the results of these examinations, 70.4% of
      graduating COM students (n=54) and 82% of allopathic graduates (n=85) failed to
      demonstrate basic competency in musculoskeletal medicine. Similarly, the majority
      of both groups failed to attain the minimum passing level established by the
      directors of internal medicine programs (graduating COM students, 67%; allopathic
      graduates, 78%). CONCLUSION: In an examination of competence levels for
      musculoskeletal medicine, students about to graduate from a COM fared only
      marginally better than did their allopathic counterparts. To ensure that all
      graduating COM students have attained a level of basic competence in
      musculoskeletal medicine, the authors recommend further study as a prelude to
      evaluation of the didactic and clinical curriculum at all 22 COMs and their
      branch campuses.

PMID- 16790544
TI  - Bifid fifth rib in a 9-year-old girl with chest pain.

PMID- 16790545
TI  - Front-line osteopathic medicine.

PMID- 16790546
TI  - In a vacuum or in a s(l)ide show: OPP in osteopathic CME programming.

PMID- 16790547
TI  - Cardiologic milestone: the automatic external defibrillator.

PMID- 16790548
TI  - Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases.
AB  - Silent Information Regulator 2 (Sir2) enzymes (or sirtuins) are NAD(+)-dependent
      deacetylases that modulate gene silencing, aging and energy metabolism. Previous
      work has implicated several transcription factors as sirtuin targets. Here, we
      investigated whether mammalian sirtuins could directly control the activity of
      metabolic enzymes. We demonstrate that mammalian Acetyl-CoA synthetases (AceCSs)
      are regulated by reversible acetylation and that sirtuins activate AceCSs by
      deacetylation. Site-specific acetylation of mouse AceCS1 on Lys-661 was
      identified by using mass spectrometry and a specific anti-acetyl-AceCS antibody.
      SIRT1 was the only member of seven human Sir2 homologues capable of deacetylating
      AceCS1 in cellular coexpression experiments. SIRT1 expression also led to a
      pronounced increase in AceCS1-dependent fatty-acid synthesis from acetate. Using
      purified enzymes, only SIRT1 and SIRT3 exhibited high catalytic efficiency
      against acetylated AceCS1. In mammals, two AceCSs have been identified:
      cytoplasmic AceCS1 and mitochondrial AceCS2. Because SIRT3 is localized to the
      mitochondria, we investigated whether AceCS2 also might be regulated by
      acetylation, and specifically deacetylated by mitochondrial SIRT3. AceCS2 was
      completely inactivated upon acetylation and was rapidly reactivated by SIRT3
      deacetylation. Lys-635 of mouse AceCS2 was identified as the targeted residue.
      Using reversible acetylation to modulate enzyme activity, we propose a model for
      the control of AceCS1 by SIRT1 and of AceCS2 by SIRT3.

PMID- 16790549
TI  - Posttranslational regulation of the mammalian circadian clock by cryptochrome and
      protein phosphatase 5.
AB  - The molecular oscillator that drives circadian rhythmicity in mammals obtains its
      near 24-h periodicity from posttranslational regulation of clock proteins.
      Activity of the major clock kinase casein kinase I (CKI) epsilon is regulated by
      inhibitory autophosphorylation. Here we show that protein phosphatase (PP) 5
      regulates the kinase activity of CKIepsilon. We demonstrate that cryptochrome
      regulates clock protein phosphorylation by modulating the effect of PP5 on
      CKIepsilon. Like CKIepsilon, PP5 is expressed both in the master circadian clock
      in the suprachiasmatic nuclei and in peripheral tissues independent of the clock.
      Expression of a dominant-negative PP5 mutant reduces PER phosphorylation by
      CKIepsilon in vivo, and down-regulation of PP5 significantly reduces the
      amplitude of circadian cycling in cultured human fibroblasts. Collectively, these
      findings indicate that PP5, CKIepsilon, and cryptochrome dynamically regulate the
      mammalian circadian clock.

PMID- 16790551
TI  - Retraction. New findings of the correlation between acupoints and corresponding
      brain cortices using functional MRI.

PMID- 16790552
TI  - Using a tritiated compound to elucidate its preclinical metabolic and excretory
      pathways in vivo: exploring tritium exchange risk.
AB  - The metabolism and excretion of N-(3R)-1-azabicyclo[2.2.2]oct-3-ylfuro[2,3
      c]pyridine-5-carboxamide (1), an agonist of the alpha7 nicotinic
      acetylcholinergic receptor, were determined in both Sprague-Dawley rats and
      beagle dogs using [3H]1. Initially, 3-tritio-furanopyridine 1 ([3H]1a) was
      evaluated in pilot mass balance studies by determining total radioactivity
      recovery and pharmacokinetics in lyophilized excreta and nonlyophilized plasma,
      respectively. Lower mass balance and much greater circulatory radioactivity
      exposures were observed in rats than in dogs, with urinary tritiated water (HTO)
      only detected in rats. The 133-h half-life in rats, possibly due to very slowly
      eliminated metabolites, was more likely attributable to HTO formed from [3H]1a
      because of site-specific chemical and/or metabolic 3H instability, which was
      confirmed by urinary HTO. In contrast, dog data supported 3H stability within
      [3H]1a. Conflicting cross-species data with [3H]1a suggested species-specific
      metabolic fates for 1, requiring a 3H form of 1 resistant to 3H loss in rats.
      Therefore, tritiation of 1 at its furanopyridine C7, a site predicted to be both
      chemically and metabolically stable, yielded 7-tritio-N-(3R)-1
      azabicyclo[2.2.2]oct-3-ylfuro[2,3-c]pyridine-5-carboxamide ditrifluoroacetate
      ([3H]1b), which allowed in both species the determination of all excretory
      pathways, total radioactivity pharmacokinetics, and major excretory and
      circulatory metabolites with complete radioactivity recovery without HTO
      generation. Definitive metabolite elucidation for 1 using [3H]1b confirmed the
      suspected species-dependent metabolic susceptibility for 3H loss from [3H]1a in
      rats, but not dogs, since the majority of rat metabolites resulted from
      furanopyridine biotransformation. The described studies explore the evaluation of
      tritium exchange risk from a mechanistic biotransformation perspective and
      highlight the need for careful deliberation when considering and designing 3H
      compounds for radiolabeled metabolism studies.

PMID- 16790550
TI  - Targeted gene disruption of methionine aminopeptidase 2 results in an embryonic
      gastrulation defect and endothelial cell growth arrest.
AB  - The antiangiogenic agent fumagillin (Fg) and its analog TNP-470 bind to
      intracellular metalloprotease methionine aminopeptidase-2 (MetAP-2) and inhibit
      endothelial cell growth in a p53-dependent manner. To confirm the role of MetAP-2
      in endothelial cell proliferation and to validate it as a physiological target
      for the Fg class of antiangiogenic agents, we have generated a conditional MetAP
      2 knockout mouse. Ubiquitous deletion of the MetAP-2 gene (MAP2) resulted in an
      early gastrulation defect, which is bypassed in double MetAP-2/p53 knockout
      embryos. Targeted deletion of MAP2 specifically in the hemangioblast lineage
      resulted in abnormal vascular development, and these embryos die at the midsomite
      stage. In addition, knockdown of MetAP-2 using small interfering RNA or
      homologous recombination specifically suppresses the proliferation of cultured
      endothelial cells. Together, these results demonstrate an essential role for
      MetAP-2 in angiogenesis and indicate that MetAP-2 is responsible for the
      endothelial cell growth arrest induced by Fg and its derivatives.

PMID- 16790553
TI  - Comparison of intrinsic clearance in liver microsomes and hepatocytes from rats
      and humans: evaluation of free fraction and uptake in hepatocytes.
AB  - Apparent intrinsic clearance (CL(int,app)) of 7-ethoxycoumarin, phenacetin,
      propranolol, and midazolam was measured using rat and human liver microsomes and
      freshly isolated and cryopreserved hepatocytes to determine factors responsible
      for differences in rates of metabolism in these systems. The cryopreserved and
      freshly isolated hepatocytes generally provided similar results, although there
      was greater variability using the latter system. The CL(int,app) values in
      hepatocytes are observed to be lower than that in microsomes, and this difference
      becomes greater for compounds with high CL(int,app). This could partly be
      attributed to the differences in the free fraction (fu). The fu in hepatocyte
      incubations (fu,hep-inc) was influenced not only by the free fraction of
      compounds in the incubation buffer (fu,buffer) but also by the rate constants of
      uptake (k(up)) and metabolism (k(met)). This report provides a new derivation for
      fu,hep-inc, which can be expressed as fu,hep-inc = [k(up)/(k(met) + k(up))]/[1 +
      (C(hep)/C(buffer)) x (V(hep)/V(buffer))], where the C(hep), C(buffer), V(hep),
      and V(buffer) represent the concentrations of a compound in hepatocytes and
      buffer and volumes of hepatocytes and buffer, respectively. For midazolam, the
      fu,hep-inc was calculated, and the maximum metabolism rate in hepatocytes was
      shown to be limited by the uptake rate.

PMID- 16790555
TI  - Human metabolism of nebicapone (BIA 3-202), a novel catechol-o-methyltransferase
      inhibitor: characterization of in vitro glucuronidation.
AB  - Nebicapone (BIA 3-202; 1-[3,4-dihydroxy-5-nitrophenyl]-2-phenylethanone), a novel
      catechol-O-methyltransferase inhibitor, is mainly metabolized by glucuronidation.
      The purpose of this study was to characterize the major plasma metabolites of
      nebicapone following p.o. administration of nebicapone to healthy volunteers, and
      to determine the human UDP-glucuronosyltransferase (UGT) enzymes involved in
      nebicapone glucuronidation. Plasma samples were collected as part of a clinical
      trial at different time points postdose and were analyzed for nebicapone and its
      metabolites using a validated method consisting of a solid-phase extraction,
      followed by high-performance liquid chromatography/mass spectrometry detection.
      The primary metabolic pathways of nebicapone in humans involve mainly 3-O
      glucuronidation, the major early metabolite, and 3-O-methylation, the predominant
      late metabolite. Of the nine commercially available recombinant UGT enzymes
      studied (UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and
      UGT2B15), only UGT1A9 exhibited high nebicapone glucuronosyltransferase specific
      activity (24.3 +/- 1.3 nmol/mg protein/min). UGT1A6, UGT1A7, UGT1A8, UGT1A10,
      UGT2B7, and UGT2B15 exhibited low activity (0.1-1.1 nmol/mg protein/min), and
      UGT1A1 and UGT1A3 showed extremely low activities (less than 0.03 nmol/mg
      protein/min). The results show that nebicapone is mainly glucuronidated in humans
      and that multiple UGT enzymes are involved in this reaction.

PMID- 16790554
TI  - Influence of nonsynonymous polymorphisms of UGT1A8 and UGT2B7 metabolizing
      enzymes on the formation of phenolic and acyl glucuronides of mycophenolic acid.
AB  - Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF),
      a standard immunosuppressive drug approved for clinical use in the prevention of
      acute allograft rejection after organ transplantation. This study examines the
      role of the genetic variants of UDP-glucuronosyltransferase (UGT) 1A8 and 2B7
      enzymes involved in the formation of the primary metabolite of MPA, the inactive
      phenolic glucuronide (MPAG), and the reactive acyl glucuronide (AcMPAG). The
      first exon of UGT1A8 was first resequenced in the region encoding for the
      substrate binding domain in 254 Caucasians and 41 African Americans. Eight
      nonsynonymous changes were observed and led to the following amino acid
      substitutions: S43L, H53N, S126G, A144V, A173G, A231T, T240A, and C277Y. Thirteen
      haplotypes were inferred, comprising only two previously described alleles,
      namely, UGT1A8*2 (A173G) and UGT1A8*3 (C277Y). Upon stable expression in human
      embryonic kidney 293 cells, the UGT1A8*3 (C277Y), *5 (G173A240), *7 (A231T), *8
      (S43L), and *9 (N53G) proteins were associated with the most profound decreases
      in the formation of MPAG and AcMPAG, indicating that these amino acids are
      critical for substrate binding and enzyme function. Altogether, the low-activity
      UGT1A8 enzymes are carried by 2.8 to 4.8% of the population. The variant of the
      UGT2B7 protein (UGT2B7*2 Y268), the main enzyme involved in the formation of
      AcMPAG, demonstrated a catalytic efficiency comparable with that of UGT2B7*1
      (H268). In conclusion, although the common UGT2B7*2 variant is predicted to have
      limited impact, several UGT1A8 variants identified may potentially account for
      the large interindividual variance in MMF pharmacokinetics and deserve further
      clinical investigations.

PMID- 16790556
TI  - Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4
      metabolism of estradiol by deployment-related and other chemicals.
AB  - Cytochromes P450 (P450s) are major catalysts in the metabolism of xenobiotics and
      endogenous substrates such as estradiol (E2). It has previously been shown that
      E2 is predominantly metabolized in humans by CYP1A2 and CYP3A4 with 2
      hydroxyestradiol (2-OHE2) the major metabolite. This study examines effects of
      deployment-related and other chemicals on E2 metabolism by human liver microsomes
      (HLM) and individual P450 isoforms. Kinetic studies using HLM, CYP3A4, and CYP1A2
      showed similar affinities (Km) for E2 with respect to 2-OHE2 production. Vmax and
      CLint values for HLM are 0.32 nmol/min/mg protein and 7.5 microl/min/mg protein;
      those for CYP3A4 are 6.9 nmol/min/nmol P450 and 291 microl/min/nmol P450; and
      those for CYP1A2 are 17.4 nmol/min/nmol P450 and 633 microl/min/nmol P450.
      Phenotyped HLM use showed that individuals with high levels of CYP1A2 and CYP3A4
      have the greatest potential to metabolize E2. Preincubation of HLM with a variety
      of chemicals, including those used in military deployments, resulted in varying
      levels of inhibition of E2 metabolism. The greatest inhibition was observed with
      organophosphorus compounds, including chlorpyrifos and fonofos, with up to 80%
      inhibition for 2-OHE2 production. Carbaryl, a carbamate pesticide, and
      naphthalene, a jet fuel component, inhibited ca. 40% of E2 metabolism.
      Preincubation of CYP1A2 with chlorpyrifos, fonofos, carbaryl, or naphthalene
      resulted in 96, 59, 84, and 87% inhibition of E2 metabolism, respectively.
      Preincubation of CYP3A4 with chlorpyrifos, fonofos, deltamethrin, or permethrin
      resulted in 94, 87, 58, and 37% inhibition of E2 metabolism. Chlorpyrifos
      inhibition of E2 metabolism is shown to be irreversible.

PMID- 16790557
TI  - On-line formation, separation, and estrogen receptor affinity screening of
      cytochrome P450-derived metabolites of selective estrogen receptor modulators.
AB  - We have developed a fully automated bioreactor coupled to an on-line receptor
      affinity detection system. This analytical system provides detailed information
      on pharmacologically active metabolites of selective estrogen receptor modulators
      (SERMs) generated by cytochromes P450 (P450s). We demonstrated this novel concept
      by investigating the metabolic activation of tamoxifen and raloxifene by P450
      containing pig and rat liver microsomes. The high resolution screening (HRS)
      system is based on the coupling of a P450-bioreactor to an HPLC-based estrogen
      receptor alpha (ERalpha) affinity assay. P450-derived metabolites of the SERMs
      were generated in the bioreactor, subsequently trapped on-line with solid phase
      extraction, and finally separated with gradient HPLC. Upon elution, the
      metabolites were screened on affinity for ERalpha with an on-line HRS assay. With
      this HRS system, we were able to follow, in a time-dependent manner, the
      formation of ERalpha-binding metabolites of tamoxifen and raloxifene. By
      analyzing the bioaffinity chromatograms with liquid chromatography-tandem mass
      spectrometry, structural information of the pharmacologically active metabolites
      was obtained as well. For tamoxifen, 15 active and 6 nonactive metabolites were
      observed, of which 5 were of primary, 10 of secondary, and 6 of an as yet unknown
      order of metabolism. Raloxifene was biotransformed in three primary and three
      secondary metabolites. MS/MS analysis revealed that three of the observed active
      metabolites of raloxifene were not described before. The present automated on
      line HRS system coupled to a P450-containing bioreactor and an ERalpha-affinity
      detector proved very efficient, sensitive, and selective in metabolic profiling
      of SERMs.

PMID- 16790558
TI  - Characterization of rat intestinal microsomal UDP-glucuronosyltransferase
      activity toward mycophenolic acid.
AB  - Mycophenolic acid (MPA) is the active immunosuppressive metabolite of the anti
      organ rejection drug mycophenolate mofetil (MMF) and is implicated in the
      gastrointestinal toxicity associated with MMF therapy. Intestinal UDP
      glucuronosyltransferases (UGT) have been proposed to provide intrinsic resistance
      against MMF-induced gastrointestinal toxicity by converting MPA to the inactive
      MPA 7-O-glucuronide. Using an optimized intestinal microsome preparation method
      that stabilized the intestinal MPA UGT activity, the MPA UGT activity of male
      Sprague-Dawley rat intestinal microsomes was characterized. A longitudinal
      gradient similar to that described for other phenolic compounds was observed,
      with the activity decreasing from the duodenum to the distal small intestine and
      colon. The catalytic efficiency of MPA glucuronidation decreased from the
      proximal to distal intestine as a result of decreasing Vmax and increasing Km.
      The finding that homozygous Gunn rats lack detectable intestinal MPA UGT activity
      indicates exclusive roles of UGT1A1, UGT1A6, and/or UGT1A7. Quantitative
      immunoblotting revealed a parallel between the MPA UGT activity and the content
      of UGT1A7-like immunoreactivity (18.7 and 7.3 microg/mg for duodenum and colon,
      respectively). In contrast, the lesser MPA-metabolizing UGT, UGT1A1 and UGT1A6,
      were lower in abundance (1.6-2.1 and 1.7-2.9 microg/mg, respectively), and their
      patterns of longitudinal distribution were distinct from the MPA UGT activity.
      These data suggest a dominant role of a UGT1A7-like enzyme, presumably UGT1A7
      itself, in the catalysis of rat intestinal MPA glucuronidation. Studies are
      ongoing to investigate the relationship between intestinal UGT1A enzymes and
      susceptibility to MMF-induced gastrointestinal toxicity.

PMID- 16790559
TI  - What happens to women who sell sex? Report of a unique occupational cohort.
AB  - BACKGROUND/OBJECTIVES: Sex work has been seen as both a health and a social
      problem. However, there is a paucity of evidence on the longer term impact on
      health. We explored the health and career paths over a period of 15 years among
      women who have worked in the sex industry. DESIGN: A longitudinal study of sex
      workers recruited between 1986 and 1993 and followed for 15 years. Outcome data
      were obtained through interview, clinic records, or third parties. SETTING:
      Clinic and community settings in London. PARTICIPANTS: We obtained outcome data
      on 130 (37%) of the original cohort of 354 women, with a combined follow up of
      1247 years. MAIN OUTCOME MEASURES: Vital status, most recent occupation, duration
      of sex work, sexually transmitted infections (STI), major health problems.
      RESULTS: The majority (73/124, 59%) were still in the sex industry and had sold
      sex for a mean of 13.6 years. There were six deaths, a mortality of 4.8 per 1000
      person years. Surviving women had a high cumulative risk (110 of 118, 93%) of
      STI. Past gonorrhoea was associated with pelvic inflammatory disease (RR 2.28,
      95% CI 1.12 to 4.66) and infertility (RR 10.9, 95% CI 1.5 to 77.3). Other
      outcomes included mental health problems (38 of 97, 40%) and addiction (46 of 72,
      64%). There were no significant differences in health outcomes between women who
      were still in the sex industry and those who had stopped. There was a high level
      of occupational mobility, and 31 women (of 84, 37%) had completed vocational or
      higher education, including eight to postgraduate level. CONCLUSIONS: Sex work is
      associated with excess mortality and morbidity including the sequelae of STI,
      mental health problems, and substance misuse. The relation between these health
      problems and sex work is complex.

PMID- 16790560
TI  - Lack of evidence for the involvement of rectal and oral trichomonads in the
      aetiology of vaginal trichomoniasis in Ghana.
AB  - OBJECTIVE: To investigate the possible involvement of human trichomonads
      (Pentatrichomonas hominis and Trichomonas tenax) other than Trichomonas vaginalis
      in the aetiology of vaginal trichomoniasis. METHODS: Vaginal swabs taken from
      women attending antenatal clinics were tested for Trichomonas vaginalis by
      traditional assays (wet-mount microscopy and InPouch culture) and nucleic acid
      amplification (polymerase chain reaction). These swabs were also tested for the
      presence of P hominis and T tenax by nucleic acid amplification. Oral and rectal
      swabs from these women were tested for T tenax and P hominis respectively. Data
      on sociodemographic characteristics, sexual and anogenital hygiene practices
      likely to seed P hominis and T tenax into the vagina were collected by a
      questionnaire. RESULTS: 93% (161) of the 173 samples in which T vaginalis was
      detected by wet preparation or culture was evaluable by PCR. Of this, T vaginalis
      was detected in 94% (152) by T vaginalis-specific PCR. Neither P hominis nor T
      tenax was detected in any of the vaginal swab samples. These included nine
      samples for which T vaginalis had been detected by wet preparation or culture,
      but were negative by T vaginalis nucleic acid amplification. P hominis and T
      tenax were not detected in any of the rectal and oral swabs, respectively.
      CONCLUSION: In this group of women, there was no evidence for the involvement of
      trichomonads other than T vaginalis in the aetiology of vaginal trichomoniasis.

PMID- 16790561
TI  - The validity of self-reported likelihood of HIV infection among the general
      population in rural Malawi.
AB  - BACKGROUND: Understanding HIV risk perception is important for designing
      appropriate strategies for HIV/AIDS prevention, because these interventions often
      rely on behaviour modification. A key component of HIV risk perception is the
      individual's own assessment of HIV status, and the extent to which this
      assessment is correct. However, this issue has received limited attention.
      OBJECTIVES: To examine the validity of self-reported likelihood of current HIV
      infection among the general population in rural Malawi. METHODS: As part of a
      panel household survey, data on behaviour and biomarkers were collected for a
      population-based sample of approximately 3000 respondents in rural Malawi aged >
      or = 15 years. Information on self-assessed likelihood of currently having HIV
      was collected by survey interview. Saliva was obtained from all consenting
      respondents to assess actual HIV status. RESULTS: Of 2299 survey respondents who
      assessed their likelihood of being infected with HIV at the time of the survey,
      71% were accurate. Most incorrect assessments (88%) were due to respondents
      overestimating (rather than underestimating) their likelihood of being infected
      with HIV. Women were less likely than men to correctly assess their HIV status.
      The two most important predictors of false-positive responses were marital status
      and self-reported health. CONCLUSIONS: Self-reports of HIV infection were
      generally valid. Most invalid self-reports were due to overestimating the risk of
      having HIV. The implications of this finding are highlighted, as they pertain to
      the design of HIV prevention interventions and the expansion of HIV counselling,
      testing and treatment programmes in developing countries.

PMID- 16790562
TI  - Disclosure of HIV status to sex partners and sexual risk behaviours among HIV
      positive men and women, Cape Town, South Africa.
AB  - BACKGROUND: The HIV epidemic continues to amplify in southern Africa and there is
      a growing need for HIV prevention interventions among people who have tested HIV
      positive. METHODS: Anonymous surveys were completed by 413 HIV-positive men and
      641 HIV-positive women sampled from HIV/AIDS services; 73% were <35 years old,
      70% Black African, 70% unemployed, 75% unmarried, and 50% taking antiretroviral
      treatment. RESULTS: Among the 903 (85%) participants who were currently sexually
      active, 378 (42%) had sex with a person to whom they had not disclosed their HIV
      status in the previous 3 months. Participants who had not disclosed their HIV
      status to their sex partners were considerably more likely to have multiple
      partners, HIV-negative partners, partners of unknown HIV status and unprotected
      intercourse with non-concordant sex partners. Not disclosing their HIV status to
      partners was also associated with having lost a job or a place to stay because of
      being HIV positive and feeling less able to disclose to partners. CONCLUSIONS:
      HIV-related stigma and discrimination are associated with not disclosing HIV
      status to sex partners, and non-disclosure is closely associated with HIV
      transmission risk behaviours. Interventions are needed in South Africa to reduce
      the AIDS stigma and discrimination and to assist people with HIV to make
      effective decisions on disclosure.

PMID- 16790563
TI  - Anal and dry sex in commercial sex work, and relation to risk for sexually
      transmitted infections and HIV in Meru, Kenya.
AB  - OBJECTIVE: To examine the practices of anal intercourse and dry sex within a
      cohort of female sex workers (FSWs) in Kenya, focusing on the prevalence and
      perceived risk of the practices, demographic and behavioural correlates, and
      association with sexually transmitted infections (STI). METHODS: A survey was
      conducted among FSWs in Meru, Kenya, with 147 participants randomly sampled from
      an existing cohort of self identified FSWs. RESULTS: 40.8% of participants
      reported ever practising anal intercourse and 36.1% reported ever practising dry
      sex. Although the majority of women surveyed believed anal intercourse and dry
      sex to be high risk practices for HIV infection compared with vaginal sex, about
      one third of women reported never or rarely using condoms during anal
      intercourse, and about 20% never or rarely using condoms during dry sex. Reported
      consistent condom use was lower with both of these practices than with penile
      vaginal intercourse. Anal intercourse was associated with experience of recent
      forced sexual intercourse, while dry sex was not. Anal intercourse was almost
      always initiated by clients, whereas dry sex was likely to be initiated by the
      women themselves. Sex workers reported charging higher fees for both practices
      than for vaginal intercourse. Both practices were associated with reported
      symptoms and diagnoses of STI. CONCLUSIONS: Both anal intercourse and dry sex
      were common in this sample, and although perceived as high risk practices, were
      not adequately protected with condom use. Education and other interventions
      regarding these high risk sexual behaviours need to be translated into safer
      practices, particularly consistent condom use, even in the face of financial
      vulnerability.

PMID- 16790564
TI  - Primer Extension Enrichment Reaction (PEER): a new subtraction method for
      identification of genetic differences between biological specimens.
AB  - We developed a conceptually new subtraction strategy for the detection and
      isolation of target DNA and/or RNA from complex nucleic acid mixtures, called
      Primer Extension Enrichment Reaction (PEER). PEER uses adapters and class IIS
      restriction enzymes to generate tagged oligonucleotides from dsDNA fragments
      derived from specimens containing an unknown target ('tester'). Subtraction is
      achieved by selectively disabling these oligonucleotides by extension reaction
      using ddNTPs and a double stranded DNA template generated from a pool of normal
      specimens ('driver'). Primers that do not acquire ddNTP are used to capture and
      amplify the unique target DNA from the original tester dsDNA. We successfully
      applied PEER to specimens containing known infectious agents (Hepatitis B Virus
      and Walrus Calicivirus) and demonstrated that it has higher efficiency than the
      best comparable technique. The strategy used for PEER is versatile and can be
      adapted for the identification of known and unknown pathogens and mutations,
      differential expression studies and other applications that allow the use of
      subtractive strategies.

PMID- 16790565
TI  - Multiple-turnover thio-ATP hydrolase and phospho-enzyme intermediate formation
      activities catalyzed by an RNA enzyme.
AB  - Ribozymes that phosphorylate internal 2'-OH positions mimic the first mechanistic
      step of P-type ATPase enzymes by forming a phospho-enzyme intermediate. We
      previously described 2'-autophosphorylation and autothiophosphorylation by the
      2PTmin3.2 ribozyme. In the present work we demonstrate that the
      thiophosphorylated form of this ribozyme can de-thiophosphorylate in the absence
      of ATPgammaS. Identical ionic conditions yield a thiophosphorylated strand when
      ATPgammaS is included, thus effecting a net ATPgammaS hydrolysis. The de
      thiophosphorylation step is nearly independent of pH over the range of 6.3-8.5
      and does not require a specifically folded RNA structure, but this step is
      greatly stimulated by transition metal ions. By monitoring thiophosphate release,
      we observe 29-46 ATPgammaS hydrolyzed per ribozyme strand in 24 h, corresponding
      to a turnover rate of 1.2-2.0 h(-1). The existence of an ATP- (or thio-ATP
      )powered catalytic cycle raises the possibility of using ribozymes to transduce
      chemical energy into mechanical work for nucleic acid nanodevices.

PMID- 16790568
TI  - Minnesota pharmacists use CPT codes.

PMID- 16790569
TI  - Four JCAHO medication management standards to change July 1.

PMID- 16790567
TI  - RNA helicases and abiotic stress.
AB  - RNA helicases function as molecular motors that rearrange RNA secondary
      structure, potentially performing roles in any cellular process involving RNA
      metabolism. Although RNA helicase association with a range of cellular functions
      is well documented, their importance in response to abiotic stress is only
      beginning to emerge. This review summarizes the available data on the expression,
      biochemistry and physiological function(s) of RNA helicases regulated by abiotic
      stress. Examples originate primarily from non-mammalian organisms while instances
      from mammalian sources are restricted to post-translational regulation of
      helicase biochemical activity. Common emerging themes include the requirement of
      a cold-induced helicase in non-homeothermic organisms, association and regulation
      of helicase activity by stress-induced phosphorylation cascades, altered nuclear
      cytoplasmic shuttling in eukaryotes, association with the transcriptional
      apparatus and the diversity of biochemical activities catalyzed by a subgroup of
      stress-induced helicases. The data are placed in the context of a mechanism for
      RNA helicase involvement in cellular response to abiotic stress. It is proposed
      that stress-regulated helicases can catalyze a nonlinear, reversible sequence of
      RNA secondary structure rearrangements which function in RNA maturation or RNA
      proofreading, providing a mechanism by which helicase activity alters the
      activation state of target RNAs through regulation of the reaction equilibrium.

PMID- 16790566
TI  - PrrC-anticodon nuclease: functional organization of a prototypical bacterial
      restriction RNase.
AB  - The tRNA(Lys) anticodon nuclease PrrC is associated in latent form with the type
      Ic DNA restriction endonuclease EcoprrI and activated by a phage T4-encoded
      inhibitor of EcoprrI. The activation also requires the hydrolysis of GTP and
      presence of dTTP and is inhibited by ATP. The N-proximal NTPase domain of PrrC
      has been implicated in relaying the activating signal to a C-proximal anticodon
      nuclease site by interacting with the requisite nucleotide cofactors [Amitsur et
      al. (2003) Mol. Microbiol., 50, 129-143]. Means described here to bypass PrrC's
      self-limiting translation and thermal instability allowed purifying an active
      mutant form of the protein, demonstrating its oligomeric structure and confirming
      its anticipated interactions with the nucleotide cofactors of the activation
      reaction. Mutagenesis and chemical rescue data shown implicate the C-proximal
      Arg320, Glu324 and, possibly, His356 in anticodon nuclease catalysis. This triad
      exists in all the known PrrC homologs but only some of them feature residues
      needed for tRNA(Lys) recognition by the Escherichia coli prototype. The
      differential conservation and consistent genetic linkage of the PrrC proteins
      with EcoprrI homologs portray them as a family of restriction RNases of diverse
      substrate specificities that are mobilized when an associated DNA restriction
      nuclease is compromised.

PMID- 16790571
TI  - Health center groups urge more technology funding.

PMID- 16790572
TI  - Quality improvement organizations and medication therapy management.

PMID- 16790573
TI  - On being a pharmacy resident.

PMID- 16790574
TI  - Tigecycline: place in therapy and important considerations.

PMID- 16790575
TI  - Tigecycline: a new glycylcycline antimicrobial agent.
AB  - PURPOSE: The pharmacology, spectrum of activity, pharmacokinetics, clinical
      efficacy, adverse events, dosage and administration, drug interactions, and place
      in therapy of tigecycline are reviewed. SUMMARY: Tigecycline is the first of a
      new class of antimicrobials, the glycylcyclines, to receive approved labeling
      from the Food and Drug Administration. Similar to tetracyclines, glycylcyclines
      contain the central four-ring carbocyclic skeleton, with a substitution at the D
      9 position. This substitution confers expanded broad-spectrum activity and
      defense against antimicrobial efflux pumps and ribosomal protection mechanisms.
      Tigecycline covers a broad spectrum of gram-positive (including resistant
      isolates), gram-negative (including extended-spectrum beta-lactamase producing
      organisms), and anaerobic pathogens. It does not exhibit activity against
      Pseudomonas aeruginosa and Proteus species. Clinical efficacy has been
      demonstrated in complicated skin and skin structure infections and intraabdominal
      infections. Tigecycline is administered intravenously and exhibits linear
      pharmacokinetics. The drug does not undergo extensive metabolism and works
      independently of the cytochrome P-450 isoenzyme system and therefore does not
      affect medications metabolized by these enzymes. Tigecycline is administered as a
      100-mg i.v. loading dose followed by 50 mg i.v. every 12 hours. Hepatic dosage
      adjustment is necessary for severe disease; however, no dosage adjustments are
      necessary for patients with renal impairment. CONCLUSION: Tigecycline is an
      alternative agent available for the treatment of resistant gram-negative and gram
      positive infections, especially in patients with a history of a penicillin
      allergy or antimicrobial-related toxicities.

PMID- 16790576
TI  - Absorbable hemostatic agents.
AB  - PURPOSE: The pharmacology, clinical efficacy, adverse effects and toxicities,
      drug interactions, dosage and administration, and safety issues related to the
      use of absorbable hemostatic agents are reviewed. SUMMARY: Absorbable hemostatic
      agents exert their pharmacologic effects at various points within the coagulation
      cascade. These agents are indicated for use during surgical procedures as
      adjunctive therapy when bleeding is not controlled by conventional methods. Early
      clinical data on absorbable hemostatic agents revealed a beneficial effect with
      regard to controlling capillary bleeding, achieving hemostasis during vascular
      surgery, and controlling bleeding from fistula-puncture sites. Few randomized
      controlled clinical trials have directly compared available agents, but case
      reports describing the efficacy of absorbable hemostatic agents in specific
      situations, especially unlabeled uses of thrombin, abound. Existing trials have
      compared the efficacy of established agents with newer agents, including fibrin
      sealants, with varying results. A variety of rarely occurring adverse effects
      have been reported with the administration of absorbable hemostatic agents; some
      of these rare effects, such as paralysis, are quite severe. No standardized
      dosing regimens are available for these agents, although surgeons may have a
      preference for a particular regimen based on their own clinical experience. No
      drug interactions involving absorbable hemostatic agents have been published;
      however, the use of these agents with other medications that affect hemostasis
      may disrupt clot formation. CONCLUSION: Absorbable hemostatic agents are useful
      as adjunctive therapy during surgical procedures when conventional methods do not
      control bleeding. Although rare adverse effects have occurred with these agents,
      their careful administration will prevent serious adverse outcomes.

PMID- 16790577
TI  - Medication access through patient assistance programs.

PMID- 16790579
TI  - A safety assessment tool for formulary candidates.

PMID- 16790578
TI  - Disposable infusion pumps.
AB  - PURPOSE: The properties, performance, and applications of nonelectric disposable
      infusion pumps are reviewed. SUMMARY: All nonelectric disposable infusion pumps
      exploit the same physical principle: mechanical restriction within the flow path
      determines the speed of pressurized fluid. The pressure generated by disposable
      pumps on fluid is 250-600 mm Hg, compared with 5-1200 mm Hg of pressure for
      electric pumps. There are several types of disposable infusion pumps, including
      elastomeric, positive-pressure (spring-powered and gas-pressure-powered),
      negative-pressure (vacuum), and patient-controlled analgesia (PCA) pumps. The
      accuracy of each pump's flow rate is dependent on several factors, including
      temperature, fluid viscosity, atmospheric pressure, back pressure, partial
      filling, and storage. Disposable infusion pumps can be used in many areas,
      including home care, PCA, patient-controlled epidural analgesia, continuous
      peripheral analgesia, continuous epidural analgesia, continuous i.v. analgesia,
      and pediatrics applications. The advantages of disposable infusion pumps include
      their light weight, small size, simplicity of use, independence from an external
      power supply, elimination of programming errors, and disposability. Disadvantages
      include the possibility of inaccurate flow rates, fixed reservoir volume, lack of
      a facility to change the flow rate and bolus-dose volume to provide adequate
      analgesia, inability to trace the history of the analgesia demand by patients,
      inability to combine PCA with background continuous infusions, and long-term
      cost. CONCLUSION: Despite some disadvantages and limited areas of applicability,
      disposable infusion pumps provide patients with advantages, such as portability,
      simplicity, and disposability, especially for the administration of analgesia.
      Understanding their physical and mechanical characteristics and their appropriate
      application may optimize patient care.

PMID- 16790580
TI  - ASHP therapeutic position statement on the institutional use of 0.9% sodium
      chloride injection to maintain patency of peripheral indwelling intermittent
      infusion devices.

PMID- 16790581
TI  - Medication use in schools.

PMID- 16790582
TI  - H. J. Muller and the "competition hoax".

PMID- 16790583
TI  - The evolution of mobile DNAs: when will transposons create phylogenies that look
      as if there is a master gene?
AB  - Some families of mammalian interspersed repetitive DNA, such as the Alu SINE
      sequence, appear to have evolved by the serial replacement of one active sequence
      with another, consistent with there being a single source of transposition: the
      "master gene." Alternative models, in which multiple source sequences are
      simultaneously active, have been called "transposon models." Transposon models
      differ in the proportion of elements that are active and in whether inactivation
      occurs at the moment of transposition or later. Here we examine the predictions
      of various types of transposon model regarding the patterns of sequence variation
      expected at an equilibrium between transposition, inactivation, and deletion.
      Under the master gene model, all bifurcations in the true tree of elements occur
      in a single lineage. We show that this property will also hold approximately for
      transposon models in which most elements are inactive and where at least some of
      the inactivation events occur after transposition. Such tree shapes are therefore
      not conclusive evidence for a single source of transposition.

PMID- 16790584
TI  - Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML.

PMID- 16790586
TI  - Thrombotic complications in patients with newly diagnosed multiple myeloma
      treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis.

PMID- 16790585
TI  - Chromosomal rearrangements involving the BCL3 locus are recurrent in classical
      Hodgkin and peripheral T-cell lymphoma.

PMID- 16790587
TI  - DMT1 mutation: response of anemia to darbepoetin administration and implications
      for iron homeostasis.

PMID- 16790588
TI  - More on prognostic significance of FLT3/ITD size in acute myeloid leukemia (AML).

PMID- 16790590
TI  - Extra force from asynchronous stimulation of cat soleus muscle results from
      minimizing the stretch of the common elastic elements.
AB  - Rack and Westbury showed that low-frequency asynchronous stimulation of a muscle
      produces greater force compared with synchronous stimulation. This study tested
      the hypothesis that the difference results from the dynamic stretch of the common
      elastic elements. In eight anesthetized cats, the soleus was attached to a
      servomechanism to control muscle length and record force. The ventral roots were
      divided into four bundles so each innervated approximately 1/4 of the soleus. The
      elasticity shared by each part of the muscle was estimated and the servomechanism
      programmed to compensate for its stretch. At each test frequency (5, 7.5, and 10
      Hz), the muscle was stimulated by asynchronous stimulation, synchronous
      stimulation, summation of force with each part stimulated individually, and
      summation with each part stimulated individually and the servomechanism mimicking
      tendon stretch during asynchronous stimulation. Muscle length was isometric
      except for the last protocol. The observed differences were small. The greatest
      difference occurred during stimulation at 5 Hz with muscle length on the
      ascending limb of the length-tension curve. Here, the average forces, normalized
      by asynchronous force, were asynchronous, 100%; synchronous, 73%; summation,
      110%; and summation with stretch compensation, 98%. The results support the
      hypothesis and suggest that the common elasticity can be used to predict force
      gains from asynchronous stimulation.

PMID- 16790591
TI  - Linear encoding of muscle activity in primary motor cortex and cerebellum.
AB  - The activity of neurons in primary motor cortex (M1) and cerebellum is known to
      correlate with extrinsic movement parameters, including hand position and
      velocity. Relatively few studies have addressed the encoding of intrinsic
      parameters, such as muscle activity. Here we applied a generalized regression
      analysis to describe the relationship of neurons in M1 and cerebellar dentate
      nucleus to electromyographic (EMG) activity from hand and forearm muscles, during
      performance of precision grip by macaque monkeys. We showed that cells in both M1
      and dentate encode muscle activity in a linear fashion, and that EMG signals
      provide predictions of neural discharge that are equally accurate to those from
      kinematic information under these task conditions. Neural activity in M1 was
      significantly more correlated with both EMG and kinematic signals than was
      activity in dentate nucleus. Furthermore, the analysis enabled us to look at the
      temporal properties of muscle encoding. Cells were broadly tuned to muscle
      activity as a function of the lag between spiking and EMG and there was
      considerable heterogeneity in the optimal delay among individual neurons.
      However, a single lag (40 ms) was generally sufficient to provide good fits.
      Finally, incorporating spike history effects in our model offered no advantage in
      predicting novel spike trains, reinforcing the simple nature of the muscle
      encoding that we observed here.

PMID- 16790592
TI  - Neuromagnetic responses to binaural beat in human cerebral cortex.
AB  - The dichotic presentation of two sinusoids with a slight difference in frequency
      elicits subjective fluctuations called binaural beat (BB). BBs provide a classic
      example of binaural interaction considered to result from neural interaction in
      the central auditory pathway that receives input from both ears. To explore the
      cortical representation of the fluctuation of BB, we recorded magnetic fields
      evoked by slow BB of 4.00 or 6.66 Hz in nine normal subjects. The fields showed
      small amplitudes; however, they were strong enough to be distinguished from the
      noise accompanying the recordings. Spectral analyses of the magnetic fields
      recorded on single channels revealed that the responses evoked by BBs contained a
      specific spectral component of BB frequency, and the magnetic fields were
      confirmed to represent an auditory steady-state response (ASSR) to BB. The
      analyses of spatial distribution of BB-synchronized responses and minimum-norm
      current estimates revealed multiple BB ASSR sources in the parietal and frontal
      cortices in addition to the temporal areas, including auditory cortices. The
      phase of synchronized waveforms showed great variability, suggesting that BB ASSR
      does not represent changing interaural phase differences (IPD) per se, but
      instead it reflects a higher-order cognitive process corresponding to subjective
      fluctuations of BB. Our findings confirm that the activity of the human cerebral
      cortex can be synchronized with slow BB by using information on the IPD.

PMID- 16790593
TI  - Extraretinal signals in MSTd neurons related to volitional smooth pursuit.
AB  - Smooth pursuit (SP)-related neurons in the dorsal-medial part of medial superior
      temporal cortex (MSTd) carry extraretinal signals that may play a role in
      maintenance of SP once eye velocity matches target velocity. For example, it has
      not been determined whether the extraretinal signals reflect volitional SP
      commands or proprioception. The aim of this study was to test some potential
      sources of extraretinal signals in MSTd pursuit neurons. We tested 40 MSTd
      neurons during step-ramp SP with target blink conditions to show that they
      carried an extraretinal signal. To examine potential contributions from eye
      movements that might reflect proprioceptive feedback from eye muscles, we tested
      MSTd neurons during rotational vestibular ocular reflex in complete darkness
      (VORd). Vestibular stimulation was delivered in the earth horizontal plane to
      elicit reflex driven smooth eye movements that matched the speed and frequency of
      volitional SP. We also tested VOR in the light (VOR x 1) and cancellation of the
      VOR (VOR x 0). Our neurons were modulated during both SP and cancellation of the
      VOR. In contrast, MSTd smooth pursuit neurons with extraretinal signals were not
      significantly modulated during VORd (sensitivity < or = 0.10 spike/s/ degrees
      /s). This combination of properties is compatible with classifying these neurons
      as gaze-velocity related. Absence of modulation during VORd testing could be
      caused by cancellation of head and eye movement sensitivity or dependence of
      neuronal firing on volitional SP commands. Our results support the suggestion
      that modulation of SP-related MSTd neurons reflects volitional SP commands rather
      then eye movements generated by reflex pathways.

PMID- 16790594
TI  - Responses to noisy periodic stimuli reveal properties of a neural predictor.
AB  - In programming motor acts, the brain must consider both internal and external
      noise sources: inherent variation in sensory estimates and changes within the
      environment. An interesting question in motor control is how reliable responses
      can be programmed in the face of noise and how these two noise sources interact.
      We study this by investigating the generation of sequences of predictive saccades
      to visual targets. First, eight normal subjects tracked targets that alternated
      at a pacing frequency (0.9 Hz) that promoted predictive behavior, for 300 trials.
      When tracking this perfectly periodic stimulus, there was variability in the
      timing of the saccades (intersaccade intervals) that was distributed around the
      interval of the stimulus (556 ms). We used this inherent variability to set the
      timing of subsequent stimuli; subjects completed three additional sessions in
      which the variance of the stimulus timing (the interstimulus intervals) had the
      same (1.0 SD), less (0.5 SD), or more (2.0 SD) variability than the subject
      displayed when tracking the perfectly periodic stimulus. Despite changes in
      stimulus timing variability, variance of the response timing (intersaccade
      intervals) was equal to the variance of the stimulus plus "inherent variance"
      (response variance when tracking a perfectly periodic stimulus). Examining the
      correlations between saccade latency and interstimulus interval, this
      relationship is interpreted as a tradeoff between reliance on previous saccade
      performance (intertrial correlations) and reliance on the current stimulus.

PMID- 16790596
TI  - Acid-sensing ionic channels in the rat vestibular endorgans and ganglia.
AB  - Acid-sensing ionic channels (ASICs) are members of the epithelial Na+
      channel/degenerin (ENaC/DEG) superfamily. ASICs are widely distributed in the
      central and peripheral nervous system. They have been implicated in synaptic
      transmission, pain perception, and the mechanoreception in peripheral tissues.
      Our objective was to characterize proton-gated currents mediated by ASICs and to
      determine their immunolocation in the rat vestibular periphery. Voltage clamp of
      cultured afferent neurons from P7 to P10 rats showed a proton-gated current with
      rapid activation and complete desensitization, which was carried almost
      exclusively by sodium ions. The current response to protons (H+) has a pH0.5 of
      6.2. This current was reversibly decreased by amiloride, gadolinium, lead,
      acetylsalicylic acid, and enhanced by FMRFamide and zinc, and negatively
      modulated by raising the extracellular calcium concentration. Functional
      expression of the current was correlated with smaller-capacitance neurons.
      Acidification of the extracellular pH generated action potentials in vestibular
      neurons, suggesting a functional role of ASICs in their excitability.
      Immunoreactivity to ASIC1a and ASIC2a subunits was found in small vestibular
      ganglion neurons and afferent fibers that run throughout the macula utricle and
      crista stroma. ASIC2b, ASIC3, and ASIC4 were expressed to a lesser degree in
      vestibular ganglion neurons. The ASIC1b subunit was not detected in the
      vestibular endorgans. No acid-pH-sensitive currents or ASIC immunoreactivity was
      found in hair cells. Our results indicate that proton-gated current is carried
      through ASICs and that ionic current activated by H+ contributes to shape the
      vestibular afferent neurons' response to its synaptic input.

PMID- 16790595
TI  - Two-dimensional coincidence detection in the vibrissa/barrel field.
AB  - Coincidence detection in visual and auditory cortex may also be critical for
      feature analysis in somatosensory cortex. We examined its role in the rat
      posteromedial barrel subfield (PMBSF) using high-resolution arrays of epipial
      electrodes. Five vibrissae, forming an arc, row, or diagonal, were simultaneously
      or asynchronously stimulated to simulate contact with a straight edge of
      different angles at natural whisking velocities. Results indicated supralinear
      responses for both slow-wave and fast oscillations (FOs, about 350 Hz) at
      intervibrissa delays <2 ms. FO represented the earliest and most precisely tuned
      response to coincident vibrissa displacement. There was little difference in the
      spatiotemporal pattern of slow-wave or FO responses in the row, arc, or diagonal.
      This equivalence of function suggests that the PMBSF may be capable of working as
      a two-dimensional integrative array, processing spatial features based on
      coincidence detection despite the direction that the vibrissae pass across an
      object.

PMID- 16790597
TI  - Plasticity of both excitatory and inhibitory synapses is associated with seizures
      induced by removal of chronic blockade of activity in cultured hippocampus.
AB  - One factor common to many neurological insults that can lead to acquired epilepsy
      is a loss of afferent neuronal input. Neuronal activity is one cellular mechanism
      implicated in transducing deafferentation into epileptogenesis. Therefore the
      effects of chronic activity blockade on seizure susceptibility and its underlying
      mechanisms were examined in organotypic hippocampal slice cultures treated
      chronically with the sodium channel blocker, tetrodotoxin (TTX), or the N-methyl
      D-aspartate receptor (NMDAR) antagonist, D-2-amino-5-phosphonovaleric acid (D
      APV). Granule cell field potential recordings in physiological buffer revealed
      spontaneous electrographic seizures in 83% of TTX-, 9% of D-APV-, but 0% of
      vehicle-treated cultures. TTX-induced seizures were not associated with membrane
      property alterations that would elicit granule cell hyperexcitability. Seizures
      were blocked by glutamate receptor antagonists, suggesting that plasticity in
      excitatory synaptic circuits contributed to seizures. The morphology of granule
      cells and their mossy fiber axons remained largely unchanged, and the number of
      synapses onto granule cells measured immunohistochemically was not increased in
      TTX- or D-APV-treated cultures. However, voltage-clamp recordings revealed that
      miniature excitatory postsynaptic current frequency and kinetics were increased
      and miniature inhibitory postsynaptic current kinetics were decreased in D-APV-
      and TTX-treated cultures compared with vehicle. Changes were more profound and
      qualitatively different in TTX- compared with D-APV-treated cultures, consistent
      with the dramatic effects of TTX treatment on seizure expression. We propose that
      chronic blockade of action potentials by TTX induces homeostatic responses
      including plasticity of both excitatory and inhibitory synapses. Removal of TTX
      unmasks the impact of these synaptic plasticities on local circuit excitability,
      resulting in spontaneous seizures.

PMID- 16790598
TI  - Circuitry and the classification of simple and complex cells in V1.
AB  - Based on a large-scale neural network model of striate cortex (V1), we present a
      simulation study of extra- and intracellular response modulations for drifting
      and contrast reversal grating stimuli. Specifically, we study the dependency of
      these modulations on the neural circuitry. We find that the frequently used ratio
      of the first harmonic to the mean response to classify simple and complex cells
      is highly insensitive to circuitry. Limited experimental sample size for the
      distribution of this measure makes it unsuitable for distinguishing whether the
      dichotomy of simple and complex cells originates from distinct LGN axon
      connectivity and/or local circuitry in V1. We show that a possible useful measure
      in this respect is the ratio of the intracellular second- to first-harmonic
      response for contrast reversal gratings. This measure is highly sensitive to
      neural circuitry and its distribution can be sampled with sufficient accuracy
      from a limited amount of experimental data. Further, the distribution of this
      measure is qualitatively similar to that of the subfield correlation coefficient,
      although it is more robust and easier to obtain experimentally.

PMID- 16790599
TI  - Development of functional synaptic connections in the auditory system visualized
      with optical recording: afferent-evoked activity is present from early stages.
AB  - A comprehensive survey of auditory network formation was performed in the brain
      stem of the chicken embryo using voltage-sensitive dye recording. Intact
      medulla/brain stem preparations with the auditory branch of the eighth nerve
      attached were dissected from 5.5- to 8-day chicken embryos, and responses evoked
      by nerve stimulation were recorded optically. In the medulla of 7- and 8-day
      embryos, we identified four response areas, corresponding to ipsilateral Nucleus
      magnocellularis (NM) and Nucleus angularis (NA), which receive the auditory
      afferents, and ipsi- and contralateral Nucleus laminaris (NL), which receive
      projections from NM. The optical responses consisted of a fast spikelike signal
      followed by a long-lasting slow signal, which reflected the sodium-dependent
      action potential and glutamatergic excitatory postsynaptic potential (EPSP),
      respectively. In NM, NA, and NL, the EPSP-related slow optical signals were
      detected from some 6-day and all 7- and 8-day preparations, indicating that
      functional synaptic connectivity in these nuclei arises by the 7-day stage. In
      the pons of 7- and 8-day embryos, we identified two additional response areas,
      which evidently correspond to ipsi- and contralateral Nucleus lemnisci lateralis
      (NLL), the higher-order nuclei of the auditory pathway. Furthermore, we detected
      optical responses from the contralateral cerebellum, which possibly correspond to
      transient projections observed only during embryogenesis. The present study
      demonstrates that functional auditory circuits are established in the chicken
      embryo at stages earlier than previously reported. We discuss the possible role
      of afferent-evoked activity with reference to auditory neural network formation.

PMID- 16790601
TI  - Intersegmental coordination during human locomotion: does planar covariation of
      elevation angles reflect central constraints?
AB  - To study intersegmental coordination in humans performing different locomotor
      tasks (backward, normal, fast walking, and running), we analyzed the
      spatiotemporal patterns of both elevation and joint angles bilaterally in the
      sagittal plane. In particular, we determined the origins of the planar
      covariation of foot, shank, and thigh elevation angles. This planar constraint is
      observable in the three-dimensional space defined by these three angles and
      corresponds to the plane described by the three time-varying elevation angle
      variables over each step cycle. Previous studies showed that this relation
      between elevation angles constrains lower limb coordination in various
      experimental situations. We demonstrate here that this planar covariation mainly
      arises from the strong correlation between foot and shank elevation angles, with
      thigh angle independently contributing to the pattern of intersegmental
      covariation. We conclude that the planar covariation of elevation angles does not
      reflect central constraints, as previously suggested. An alternative approach for
      analyzing the patterns of coordination of both elevation and joint (hip, knee,
      and ankle) angles is used, based on temporal cross-correlation and phase
      relationships between pairs of kinematic variables. We describe the changes in
      the pattern of intersegmental coordination that are associated with the changes
      of locomotor modes and locomotor speeds. We provide some evidence for a distinct
      control of thigh motion and discuss the respective contributions of passive
      mechanical factors and of active (arising from neural control) factors to the
      formation and the regulation of the locomotor pattern throughout the gait cycle.

PMID- 16790600
TI  - Global electrosensory oscillations enhance directional responses of midbrain
      neurons in eigenmannia.
AB  - Eigenmannia, a genus of weakly electric fish, exhibits a specialized behavior
      known as the jamming avoidance response (JAR). The JAR results in a categorical
      difference between Eigenmannia that are in groups of conspecifics and those that
      are alone. Fish in groups exhibit the JAR behavior and thereby experience
      ongoing, global synchronous 20- to 50-Hz electrosensory oscillations, whereas
      solitary fish do not. Although previous work has shown that these ongoing signals
      do not significantly degrade electrosensory behavior, these oscillations
      nevertheless elicit short-term synaptic depression in midbrain circuits. Because
      short-term synaptic depression can have profound effects on the transmission of
      information through synapses, we examined the differences in intracellularly
      recorded responses of midbrain neurons in awake, behaving fish to moving
      electrosensory images under electrosensory conditions that mimic solitary fish
      and fish in groups. In solitary conditions, moving objects elicited Gaussian or
      sinusoidal postsynaptic potentials (PSPs) that commonly exhibited preferential
      responses to a direction of motion. Surprisingly, when the same stimulus was
      presented in the presence of the global oscillations, directional selectivity was
      increased in all neurons tested. The magnitudes of the differences in PSP
      amplitude for preferred and nonpreferred directions were correlated with a
      measure of short-term synaptic depression in both conditions. The electrosensory
      consequences of the JAR appear to result in an enhancement of the representation
      of direction of motion in midbrain neurons. The data also support a role for
      short-term synaptic depression in the generation and modulation of directional
      responses.

PMID- 16790602
TI  - Implications of functionally different synaptic inputs for neuronal gain and
      computational properties of fly visual interneurons.
AB  - Neurons embedded in networks are thought to receive synaptic inputs that do not
      drive them on their own, but modulate the responsiveness to driving input.
      Although studies on brain slices have led to detailed knowledge of how nondriving
      input affects dendritic integration, its origin and functional implications
      remain unclear. We tackle this issue using an ensemble of fly wide-field visual
      interneurons. These neurons offer the opportunity not only to combine in vivo
      recording techniques and natural sensory stimulation but also to interpret
      electrophysiological results in a behavioral context. By targeted manipulation of
      the animal's visual input we find a pronounced modulating impact of nondriving
      input, whereas functionally important cellular properties like direction tuning
      and the coding of pattern velocity are left almost unaffected. We propose that
      the integration of functionally different synaptic inputs is a mechanism that
      immanently equalizes the ensemble's sensitivity irrespective of the specific
      stimulus conditions.

PMID- 16790603
TI  - Reduction of intracortical inhibition in soleus muscle during postural activity.
AB  - Short-interval intracortical inhibition (SICI) decreases during voluntary
      contraction of the target muscle. It is unknown whether this effect also occurs
      with postural contractions. We have compared the effects of voluntary and
      postural contractions on SICI in the soleus (SOL) muscle. We applied transcranial
      magnetic stimuli (TMS) in subjects under three tasks: sitting at rest (Rest),
      sitting while activating the SOL muscle (Voluntary), or standing quietly
      (Postural). In control trials, we applied suprathreshold TMS to obtain
      unconditioned motor-evoked potentials (MEPs). In test trials, the same TMS was
      preceded by a subthreshold TMS at different interstimulus intervals (ISIs), to
      obtain a conditioned MEP. SICI and intracortical facilitation (ICF) were
      expressed as the decrease or increase in MEP size relative to unconditioned MEPs.
      There was significant effect of task in mean SICI or mean ICF in SOL. Mean SICI
      in SOL was 52% in Rest and decreased to 21% in Voluntary and 15% in Postural.
      Mean ICF in SOL was 132% and decreased to 113% in Voluntary and to 108% in
      Postural. Mean SICI in SOL was not different in Voluntary and Postural tasks.
      There was no effect of task in mean SICI or mean ICF in TA. Our results indicate
      that decrease of SICI with muscle contraction occurs to a similar extent with
      tonic voluntary and postural activation, suggesting that those contractions
      require a similar type of cortical involvement. However, it cannot be excluded
      that some part of the SICI reduction with muscle contraction depends on changes
      in segmental excitability.

PMID- 16790604
TI  - Neural mechanisms underlying selectivity for the rate and direction of frequency
      modulated sweeps in the inferior colliculus of the pallid bat.
AB  - This study describes mechanisms that underlie neuronal selectivity for the
      direction and rate of frequency-modulated sweeps in the central nucleus of the
      inferior colliculus (ICC) of the pallid bat (Antrozous pallidus). This ICC
      contains a high percentage of neurons (66%) that respond selectively to the
      downward sweep direction of the bat's echolocation pulse. Some (19%) are
      specialists that respond only to downward sweeps. Most neurons (83%) are also
      tuned to sweep rates. A two-tone inhibition paradigm was used to describe
      inhibitory mechanisms that shape selectivity for sweep direction and rate. Two
      different mechanisms can create similar rate tuning. The first is an early on
      best frequency inhibition that shapes duration tuning, which in turn determines
      rate tuning. In most neurons that are not duration tuned, a delayed high
      frequency inhibition creates rate tuning. These neurons respond to fast sweep
      rates, but are inhibited as rate slows, and delayed inhibition overlaps
      excitation. In these neurons, starting a downward sweep within the excitatory
      tuning curve eliminates rate tuning. However, if rate tuning is shaped by
      duration tuning, this manipulation has no effect. Selectivity for the downward
      sweep direction is created by an early low-frequency inhibition that prevents
      responses to upward sweeps. In addition to this asymmetry in arrival times of low
      and high-frequency inhibitions, the bandwidth of the low-frequency sideband was
      broader. Bandwidth influences the arrival time of inhibition during an FM sweep
      because a broader sideband will be encountered sooner. These findings show that
      similar spectrotemporal filters can be created by different mechanisms.

PMID- 16790605
TI  - Glucocerebrosidase mutations are an important risk factor for Lewy body
      disorders.
AB  - The synucleinopathies are neurodegenerative disorders defined by inclusions
      composed of aberrantly fibrillized alpha-synuclein, but factors contributing to
      this process remain largely unknown. The authors examined the glucocerebrosidase
      gene in 75 autopsy specimens with different synucleinopathies and identified
      mutations in 23% of cases of dementia with Lewy bodies, expanding on previous
      findings in subjects with Parkinson disease. Mutations in this lysosomal protein
      may interfere with the clearance or promote aggregation of alpha-synuclein.

PMID- 16790606
TI  - Valosin-containing protein gene mutations: clinical and neuropathologic features.
AB  - BACKGROUND: Hereditary inclusion body myopathy (IBMPFD) with Paget disease of
      bone (PDB) and frontotemporal dementia (FTD) is a rare multisystem disorder with
      autosomal dominant inheritance. Recently, missense mutations in the gene encoding
      valosin-containing protein (VCP) have been found in individuals with IBMPFD.
      VCP/P97, which exerts a variety of cellular functions, plays a key role in the
      ubiquitin-proteasome dependent degradation of cytosolic proteins and in the
      retrotranslocation of misfolded proteins from the endoplasmic reticulum into the
      cytoplasm. METHODS: The authors describe the clinical features of two kindreds in
      which VCP R93C and R155C missense mutations segregate and perform a
      histopathologic examination of brain, muscle, bone, and liver of three subjects
      harboring the R155C mutation. RESULTS: Frontotemporal dementia was present in
      100% of affected subjects in Family F1 and 70% in Family F2, as compared with an
      average of 30% in previously described IBMPFD families. In contrast, PDB was a
      more inconstant clinical feature. Biochemical and histopathologic data are
      consistent with the hypothesis that VCP R155C mutation disrupts normal VCP
      function, leading to diffuse accumulation of ubiquitinated proteins within the
      cells. CONCLUSIONS: VCP mutations are present in two families in which FTD is the
      most prominent symptom. The histopathologic study performed in patients harboring
      the R155C mutation supports the hypothesis that this mutation disrupts normal VCP
      function, leading to diffuse accumulation of ubiquitinated proteins within the
      cells. IBMPFD belongs to a class of genetic diseases associated with an
      alteration of the ubiquitin-proteasome system.

PMID- 16790607
TI  - A double-blind, randomized controlled trial on the use of a 50:50 mixture of
      nitrous oxide/oxygen in pain relief during suction evacuation for the first
      trimester pregnancy termination.
AB  - BACKGROUND: This prospective study assessed the role of a 50:50 mixture of
      nitrous oxide (N2O) and oxygen for pain relief during the termination of first
      trimester pregnancies by suction evacuation under conscious sedation. METHODS:
      Ninety women undergoing suction evacuation up to 12 weeks of gestation were
      randomized by a computer-generated randomization list and allocated using sealed
      envelopes to receive the N2O/O2 mixture or air during the operation. Pain scores
      during and after suction evacuation, post-operative side effects and satisfaction
      level were compared. RESULTS: No statistically significant differences in pain
      scores, post-operative side effects and satisfaction levels were found between
      the two groups. CONCLUSION: N2O/O2 did not reduce the pain level during suction
      evacuation for the first trimester pregnancy termination under conscious
      sedation.

PMID- 16790608
TI  - Reproductive performance, pain recurrence and disease relapse after conservative
      surgical treatment for endometriosis: the predictive value of the current
      classification system.
AB  - BACKGROUND: To assess the predictive value of the current classification of
      endometriosis in terms of response to surgical treatment, we studied to what
      extent disease stage, lesion type and lesion site were associated with post
      operative pregnancy rate, symptom recurrence and disease relapse. METHODS: A
      total of 729 women with endometriosis undergoing first-line conservative
      laparoscopic surgery were included. Data on age at surgery, disease stage
      according to the revised American Fertility Society (AFS) classification,
      anatomical characteristics of endometriotic lesions, fertility status and types
      and severity of pain symptoms were collected. RESULTS: Minimal endometriosis was
      present in 222 patients, mild in 106, moderate in 197 and severe in 204. The
      cumulative probability of pregnancy at 3 years from surgery in 537 infertile
      women was 47% (51% at stage I, 45% at stage II, 46% at stage III and 44% at stage
      IV; log-rank test, chi(2)3=1.50, P=0.68). The cumulative probability of moderate
      or severe dysmenorrhoea recurrence in 425 symptomatic subjects was 24% (32% at
      stage I, 24% at stage II, 21% at stage III and 19% at stage IV; log-rank test,
      chi2(3)=6.39, P=0.094). The cumulative probability of disease relapse was 12% (3%
      at stage I, 11% at stage II, 11% at stage III and 23% at stage IV; log-rank test,
      chi(2)3=24.95, P=0.0001). Using Cox's multivariate proportional hazards
      regression analysis, no association was observed between endometriosis stage or
      lesion type and lesion site and any of the considered study outcomes.
      CONCLUSIONS: The current classification of endometriosis has an inadequate
      predictive value with regard to the major clinical outcomes.

PMID- 16790609
TI  - Complement as a predictor of further miscarriage in couples with recurrent
      miscarriages.
AB  - BACKGROUND: The clinical significance of complement is unclear in patients with
      unexplained recurrent miscarriage, though low levels of complement 3 (C3) and/or
      complement 4 (C4) are reported to be associated with the antiphospholipid
      syndrome (aPS). We therefore investigated whether C3 and C4 have a predictive
      value for subsequent miscarriages. METHODS: In total, 215 patients with a history
      of two consecutive first-trimester miscarriages and no abnormal chromosomes in
      either partner, no uterine anomalies and no antiphospholipid (aPL) antibodies
      were examined. Blood tests for C3, C4, total haemolytic complement (CH50),
      immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) were
      performed before subsequent pregnancy. Patients were then followed up without
      treatment, and their pregnancy outcomes were compared with their previous blood
      test results. RESULTS: From 215 pregnant patients, 45 subsequently miscarried,
      whereas the remainder had a live birth. There was no relation with serum CH50,
      IgG, IgA and IgM levels, but C3 and C4 levels in patients with subsequent
      miscarriage were significantly higher than in those whose pregnancy was
      successful. CONCLUSION: In patients with two previous miscarriages, C3 and C4
      levels were higher in those women who had a third miscarriage, than in women that
      went on to have a live birth.

PMID- 16790610
TI  - There is no role for uterine curettage in the contemporary diagnostic workup of
      women with a pregnancy of unknown location.
AB  - BACKGROUND: The aim of this study was to generate and evaluate a new protocol
      that defined non-viability in the pregnancy of unknown location (PUL) population
      and therefore ensured no viable intra-uterine pregnancy (IUP) would be
      interrupted if uterine curettage was performed. A secondary aim was to evaluate
      published biochemical criteria that define non-viability in a PUL population to
      establish if these criteria could result in inadvertent termination of pregnancy
      (TOP) if uterine curettage was performed. METHODS: All clinically stable women
      classified as having a PUL were included in this study. Protocol 1 was developed
      retrospectively based on data from 500 consecutive PULs. Using this protocol, no
      cases of viable IUPs would undergo uterine curettage and the potential for TOP
      was eliminated. This protocol was then validated prospectively on the data from a
      further 503 consecutive PULs. Results were then compared with three established
      criteria (Protocols 2-4) for the use of uterine curettage as a diagnostic tool to
      classify the location of PULs. Protocol 2 defined non-viability when the hCG
      ratio (hCG at 48 h/hCG at 0 h) was <or=1.66; Protocol 3 advised uterine curettage
      at serum hCG levels of >or=2000 U/l or when the initial serum hCG was <2000 U/l
      with a serum hCG rise of <35% over 48 h (hCG ratio<1.35); Protocol 4 advised
      uterine curettage with a serum hCG rise of <50% over 48 h (hCG ratio<1.50). The
      number of uterine curettages performed and viable IUPs that would have undergone
      an unplanned TOP were recorded for all protocols. RESULTS: A total of 12 572
      consecutive women were scanned: 1003 (8.0%) women were classified as PULs.
      Training set consisted of 500 PULs: 278 (55.6%) failing PULs, 176 (35.2%) IUPs
      and 46 (9.2%) ectopic pregnancies (EPs). Test set consisted of 503 PULs: 255
      (50.7%) failing PULs, 203 (40.4%) IUPs and 45 (9.0%) EPs. Protocol 1 when
      developed retrospectively on the training set would have resulted in 293 uterine
      curettages and no potential TOP. Protocol 1 tested prospectively on 503 PULs
      would have resulted in 272 uterine curettages and no potential TOP. Three
      established criteria were tested on the entire data set (n=1003). Protocol 2
      would have resulted in 114 uterine curettages and 14 (12.3%) potential TOPs;
      Protocol 3 would have led to 611 uterine curettages and seven (1.2%) potential
      TOPs; Protocol 4 would have resulted in 617 uterine curettages and three (0.5%)
      potential TOPs. No harm came to the women whose EP diagnosis was delayed.
      CONCLUSIONS: Established criteria for the use of uterine curettage in the
      management of PULs, including those advocated by the American Society for
      Reproductive Medicine (ASRM), can theoretically result in an inadvertent TOPs. On
      the basis of these data, a change in contemporary clinical practice should be
      considered to avoid further damage to wanted pregnancies. We conclude that
      uterine curettage should not be used in the routine diagnostic workup of women
      with a PUL.

PMID- 16790611
TI  - Temporal expression profiling of the uterine luminal epithelium of the pseudo
      pregnant mouse suggests receptivity to the fertilized egg is associated with
      complex transcriptional changes.
AB  - BACKGROUND: The molecular basis of changes underlying the altered sensitivity of
      the uterine luminal epithelium (LE) to the embryo over the peri-implantation
      period is not fully understood. METHODS: Microarray analysis was performed on
      purified LE isolated from the pseudo-pregnant mouse uterus at 12-h intervals from
      pre-receptivity through the implantation window to refractoriness. The aim was to
      identify genes whose expression changes in the LE during this period. RESULTS: A
      total of 447 transcripts were identified whose abundance changed more than 2-fold
      in the LE but which did not change in the underlying stroma (S) and glands. Six
      major patterns of changing expression were noted. Of the 447 genes, 140 were
      expressed in LE at least 15-fold higher than in S and glandular epithelium (GE)
      (101 of these more than 20-fold). Detailed spatiotemporal expression profiles
      were derived for several genes previously implicated in implantation (including
      Edg7, Ptgs1, Pla2g4a and Alox15). CONCLUSIONS: Functional changes in LE
      receptivity are characterized by changing constellations of gene expression. Pre
      receptivity has a different molecular footprint to refractoriness. Because we
      have used the pseudo-pregnant mouse model, these changes are driven solely by
      endocrine signals rather than events downstream of embryo attachment. Some of
      these genes have been described in previous microarray studies on endometrium,
      but for the majority, this is the first time they have been implicated in
      implantation. The 140 genes enriched in the LE greatly expand the list of
      epithelial markers and provide many novel candidates for further studies to
      identify genes playing important roles in receptivity and embryo attachment.

PMID- 16790612
TI  - Developmental and functional evidence of nuclear immaturity in prepubertal
      oocytes.
AB  - BACKGROUND: The nuclear compartment has been proposed as responsible for the
      developmental arrest of prepubertal mouse oocytes while the studies on
      prepubertal sheep and cow oocyte model suggested the cytoplasm immaturity
      accounts for this failure. METHODS: The apparent disagreement on the causes of
      developmental defects between these two species prompted us to study: (i)
      follicular and oocyte growth allometry in lambs, (ii) oocyte compartment (nucleus
      versus cytoplasm) responsible for developmental failure by nucleus exchange
      between lamb and adult sheep oocytes, (iii) nucleolar features of prepubertal
      oocytes by ultrastructural observation and (iv) in vivo developmental survey of
      prepubertally derived embryos. RESULTS: The oocyte growth inside the follicle is
      asynchronous during prepuberty. The nuclear transfer revealed that the lamb
      nucleus was responsible for developmental failure. Immature fibrillogranular
      structure of the nucleolus has been revealed in small lamb oocytes and also in a
      few adult-size lamb oocytes. Studies in vivo revealed a high occurrence of
      developmental arrest of prepubertal derived fetuses, which we have attributed to
      the low genome-wide methylation detected in prepubertal oocytes. CONCLUSIONS: Our
      studies have indicated incomplete nuclear maturation of prepubertal gamete. The
      implication of this finding suggests caution when the strategy of rescue of
      prepubertal oocytes for assisted fertilization is considered such as in the case
      of therapeutic treatment which precludes the maintenance of fertility of sexually
      immature patients.

PMID- 16790613
TI  - The need for interaction between assisted reproduction technology and genetics:
      recommendations of the European Societies of Human Genetics and Human
      Reproduction and Embryology.
AB  - Infertility and reproductive genetic risk are both increasing in our societies
      because of lifestyle changes and possibly environmental factors. Owing to the
      magnitude of the problem, they have implications not only at the individual and
      family levels but also at the community level. This leads to an increasing demand
      for access to assisted reproduction technology (ART) and genetic services,
      especially when the cause of infertility may be genetic in origin. The increasing
      application of genetics in reproductive medicine and vice versa requires closer
      collaboration between the two disciplines. ART and genetics are rapidly evolving
      fields where new technologies are currently introduced without sufficient
      knowledge of their potential long-term effects. As for any medical procedures,
      there are possible unexpected effects which need to be envisaged to make sure
      that the balance between benefits and risks is clearly on the benefit side. The
      development of ART and genetics as scientific activities is creating an
      opportunity to understand the early stages of human development, which is leading
      to new and challenging findings/knowledge. However, there are opinions against
      investigating the early stages of development in humans who deserve respect and
      attention. For all these reasons, these two societies, European Society of Human
      Genetics (ESHG) and European Society of Human Reproduction and Embryology
      (ESHRE), have joined efforts to explore the issues at stake and to set up
      recommendations to maximize the benefit for the couples in need and for the
      community.

PMID- 16790614
TI  - Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially
      restores the expression of endometrial integrin beta3 and leukaemia-inhibitory
      factor and improves uterine receptivity in mice.
AB  - BACKGROUND: The impact of different ovarian stimulation (OS) protocols on
      endometrial receptivity remains controversial. In this study, the effects of
      different OS on the expression of endometrial integrin beta3 subunit and
      leukaemia-inhibitory factor (LIF) during the implantation window and the
      implantation rate in mice were investigated. METHODS: Three OS protocols were
      used, involving either pregnant mare's serum gonadotrophin (PMSG) alone, PMSG
      plus GnRH agonist or PMSG plus GnRH antagonist. Uterus samples were collected at
      48 h after OS or ovulation and were detected with immunohistochemistry, Western
      blot and RT-PCR analyses. Normal embryos at gestation day 4 were transferred into
      the uteri of mice in the control and OS groups. RESULTS: All OS groups showed a
      significant decrease in the expression of both the endometrial integrin beta3
      subunit and LIF during the implantation window and the implantation rate. Among
      the three OS groups, GnRH agonist-treated mice showed a higher endometrial
      integrin beta3 subunit and LIF expression and a higher implantation rate. No
      significant difference was found in the measured indices between the GnRH
      antagonist and PMSG groups. CONCLUSIONS: OS may inhibit the expression of
      endometrial integrin beta3 subunit and LIF and impair endometrial receptivity in
      mice. OS with GnRH agonist, but not GnRH antagonist, may partially restore the
      endometrial physiological secretion and improve uterine receptivity.

PMID- 16790616
TI  - The hemodynamic effects of methylene blue when administered at the onset of
      cardiopulmonary bypass.
AB  - Hypotension occurs during cardiopulmonary bypass (CPB), in part because of
      induction of the inflammatory response, for which nitric oxide and guanylate
      cyclase play a central role. In this study we examined the hemodynamic effects of
      methylene blue (MB), an inhibitor of guanylate cyclase, administered during
      cardiopulmonary bypass (CPB) to patients taking angiotensin-converting enzyme
      inhibitors. Thirty patients undergoing cardiac surgery were randomized to receive
      either MB (3 mg/kg) or saline (S) after institution of CPB and cardioplegic
      arrest. CPB was managed similarly for all study patients. Hemodynamic data were
      assessed before, during, and after CPB. The use of vasopressors was recorded. All
      study patients experienced a similar reduction in mean arterial blood pressure
      (MAP) and systemic vascular resistance (SVR) with the onset of CPB and
      cardioplegic arrest. MB increased MAP and SVR and this effect lasted for 40
      minutes. The saline group demonstrated a persistently reduced MAP and SVR
      throughout CPB. The saline group received phenylephrine more frequently during
      CPB, and more norepinephrine after CPB to maintain a desirable MAP. The MB group
      recorded significantly lower serum lactate levels despite equal or greater MAP
      and SVR. In conclusion, administration of MB after institution of CPB for
      patients taking angiotensin-converting enzyme inhibitors increased MAP and SVR
      and reduced the need for vasopressors. Furthermore, serum lactate levels were
      lower in MB patients, suggesting more favorable tissue perfusion.

PMID- 16790615
TI  - The effect of small intramural uterine fibroids on the cumulative outcome of
      assisted conception.
AB  - BACKGROUND: This study aimed to evaluate the effect of small intramural fibroids
      on the cumulative pregnancy, ongoing pregnancy, live birth and implantation rates
      after three IVF/ICSI attempts. METHODS: The first three treatment cycles of women
      enrolled for IVF/ICSI over a 12-month period were analysed. Only patients with
      small (<or=5 cm) intramural fibroids not encroaching upon the endometrial cavity
      were included in the fibroid group. Cox's hazards regression was used to estimate
      the hazard ratio (HR) associated with the presence of intramural fibroids.
      RESULTS: During the study period, 322 women without fibroids (control group) and
      112 women with fibroids (study group) underwent 606 IVF/ICSI cycles. The
      pregnancy, ongoing pregnancy and live birth rates in the study group were 23.6,
      18.8 and 14.8% compared with 32.9, 28.5 and 24% in the control group,
      respectively (P<0.05). Cox regression analysis showed that the pregnancy rate at
      each cycle was reduced by 39% (HR=0.61, 95% CI=0.39-0.95, P=0.029) in the study
      group compared with the control group. The cumulative ongoing pregnancy rate was
      reduced by 43% (HR=0.57, 95% CI=0.35-0.91, P=0.018), and the cumulative live
      birth rate was reduced by 47% (HR=0.53, 95% CI=0.32-0.87, P=0.013) in the study
      group. After adjusting for confounding variables, the presence of fibroids was
      found to significantly reduce the ongoing pregnancy rate at each cycle of
      IVF/ICSI by 40% (HR=0.60, 95% CI=0.36-0.99, P=0.048) and the live birth rate at
      each cycle by 45% (HR=0.55, 95% CI=0.32-0.95, P=0.03). CONCLUSION: Small
      intramural fibroids are associated with a significant reduction in the cumulative
      pregnancy, ongoing pregnancy and live birth rates after three IVF/ICSI cycles.

PMID- 16790617
TI  - The coronary and myocardial effects of remifentanil and sufentanil in the
      erythrocyte-perfused isolated rabbit heart.
AB  - Remifentanil-induced hypotension may be associated with adverse ischemic
      myocardial events. Although these events can be easily attributed to a decrease
      in coronary pressure perfusion, we tested the hypothesis that remifentanil could
      directly affect coronary vasomotor tone. Therefore, we assessed intrinsic
      coronary and myocardial in vitro effects of remifentanil on a Langendorff's
      rabbit model and compared these effects with those provoked by similar
      intracoronary concentrations of sufentanil. Under general anesthesia, hearts from
      New Zealand rabbits were rapidly excised and mounted on an erythrocyte-perfused
      and isolated heart preparation. The hearts were then exposed to increasing
      concentrations (10-1000 nM) of either remifentanil (n = 10) or sufentanil (n =
      8). Between each concentration, hearts were allowed to return to baseline status.
      The maximal coronary and myocardial effects of each concentration of both drugs
      were noted. Baseline values of coronary blood flow and myocardial performances
      were comparable between groups. Neither remifentanil nor sufentanil induced
      significant coronary and myocardial effects. These results suggest that
      myocardial ischemia, which may occur during remifentanil-induced hemodynamic
      disturbances, especially in cardiac patients, is only related to a decrease in
      coronary perfusion pressure provoked by peripheral hemodynamic changes.

PMID- 16790618
TI  - The association between duration of storage of transfused red blood cells and
      morbidity and mortality after reoperative cardiac surgery.
AB  - Red blood cells (RBCs) undergo numerous changes during storage; however, the
      clinical relevance of these storage "lesions" is unclear. We hypothesized that
      the duration of storage of transfused RBCs is associated with mortality after
      repeat sternotomy for cardiac surgery, because these patients are at high risk
      for both RBC transfusion and adverse outcome. We retrospectively analyzed 434
      patients who underwent repeat median sternotomy for coronary artery bypass graft
      or valve surgery and who received allogeneic RBCs. Three-hundred-twenty-one (74%)
      patients met the criteria for eligibility. After adjusting for the effects of
      confounders and the total number of RBC transfusions, the duration of storage of
      the oldest RBC unit transfused was found to be associated with both in-hospital
      mortality (Cox proportional hazard ratio (HR) = 1.151; P < 0.0001) and out-of
      hospital mortality (HR = 1.116; P < 0.0001). The mean duration of storage of
      transfused RBCs was also an independent predictor of in-hospital mortality (HR =
      1.036; P < 0.0001). Independent associations between the duration of storage of
      transfused RBCs and acute renal dysfunction and intensive care unit and hospital
      length of stay were also observed. The duration of storage of RBCs is associated
      with adverse outcome after repeat sternotomy for cardiac surgery. The clinical
      significance of this finding should be investigated in a large, randomized,
      blinded clinical trial.

PMID- 16790620
TI  - Transesophageal echocardiography for the diagnosis and management of massive
      pulmonary embolism.

PMID- 16790621
TI  - Detection of an ill-poised thread of lint by transesophageal echocardiography
      after aortic valve replacement.

PMID- 16790619
TI  - Cardiopulmonary bypass management and neurologic outcomes: an evidence-based
      appraisal of current practices.
AB  - Neurologic complications after cardiac surgery are of growing importance for an
      aging surgical population. In this review, we provide a critical appraisal of the
      impact of current cardiopulmonary bypass (CPB) management strategies on
      neurologic complications. Other than the use of 20-40 microm arterial line
      filters and membrane oxygenators, newer modifications of the basic CPB apparatus
      or the use of specialized equipment or procedures (including hypothermia and
      "tight" glucose control) have unproven benefit on neurologic outcomes. Epiaortic
      ultrasound can be considered for ascending aorta manipulations to avoid atheroma,
      although available clinical trials assessing this maneuver are limited. Current
      approaches for managing flow, arterial blood pressure, and pH during CPB are
      supported by data from clinical investigations, but these studies included few
      elderly or high-risk patients and predated many other contemporary practices.
      Although there are promising data on the benefits of some drugs blocking
      excitatory amino acid signaling pathways and inflammation, there are currently no
      drugs that can be recommended for neuroprotection during CPB. Together, the
      reviewed data highlight the deficiencies of the current knowledge base that
      physicians are dependent on to guide patient care during CPB. Multicenter
      clinical trials assessing measures to reduce the frequency of neurologic
      complications are needed to develop evidence-based strategies to avoid increasing
      patient morbidity and mortality.

PMID- 16790622
TI  - Large coronary arteriovenous fistula to the main pulmonary artery.

PMID- 16790623
TI  - Pediatric research and scholarship: another Gordian knot?

PMID- 16790624
TI  - Pediatric drug development in anesthesiology: an FDA perspective.

PMID- 16790625
TI  - The use of dexmedetomidine in pediatric cardiac surgery.
AB  - We tested dexmedetomidine, an alpha2 agonist, for its ability to decrease heart
      rate, arterial blood pressure, and neuroendocrinal responses during pediatric
      cardiac surgery. In a randomized, placebo-controlled study, 30 pediatric patients
      undergoing open heart surgery were randomly assigned to one of two equal groups.
      The control group received saline, whereas the treatment group (DEX group)
      received an initial bolus dose of dexmedetomidine (0.5 microg/kg) over 10 min,
      followed immediately by a continuous infusion of 0.5 microg.kg(-1).h(-1).
      Arterial blood pressure, heart rate, and sequential concentrations of circulating
      cortisol, epinephrine, norepinephrine, and blood glucose were measured. Relative
      to baseline, arterial blood pressure and heart rate decreased significantly after
      the administration of dexmedetomidine through skin incision. In the control
      group, patients' heart rate and arterial blood pressure measures increased after
      skin incision until the end of bypass (P < 0.05). In both groups, plasma
      cortisol, epinephrine, norepinephrine, and blood glucose increased significantly
      relative to baseline, after sternotomy, and after bypass. However, the values
      were significantly higher in the control group compared with the DEX group (P <
      0.05). In conclusion, intraoperative dexmedetomidine infusion attenuated the
      hemodynamic and neuroendocrinal response to surgical trauma and cardiopulmonary
      bypass in pediatric patients undergoing corrective surgery for congenital heart
      disease.

PMID- 16790626
TI  - Dexmedetomidine for pediatric sedation for computed tomography imaging studies.
AB  - Dexmedetomidine is a sedative with limited experience in the pediatric
      population. This is the first study that prospectively evaluates the sedation
      profile of a dexmedetomidine pilot program for pediatric sedation for
      radiological imaging studies. In March 2005, our hospital sedation committee
      approved the replacement of IV pentobarbital with dexmedetomidine as the standard
      of care for CT imaging. Detailed Quality Assurance (QA) data sheets collect
      relevant information on each patient, which is then logged into a computerized
      sedation database. After IRB approval, all QA data was accessed. Sixty-two
      patients with a mean age of 2.8 years (SD = 1.8, range 0.5-9.7) received IV (IV)
      dexmedetomidine administered as a 2 mcg/kg loading dose over 10 minutes, followed
      by repeat boluses of 2 mcg/kg over 10 minutes until target of Ramsay Sedation
      Score 4 (RSS) achieved. Patients were then maintained on 1 mcg/kg/hr infusion
      until imaging is completed. Repeated-measures ANOVA indicated that compared to
      pre-sedation values, the heart rate and mean arterial blood pressure decreased an
      average of 15% during bolus, infusion and recovery (P < 0.01). No significant
      changes were observed in respiratory rate or end-tidal CO2. Mean recovery time
      was 32 +/- 18 minutes. Based on our pilot results, dexmedetomidine may provide a
      reliable and effective method of providing sedation.

PMID- 16790628
TI  - Short duration large dose dexmedetomidine in a pediatric patient during
      procedural sedation.
AB  - We describe an infusion of dexmedetomidine at 1.0 microg.kg(-1).min(-1) for 10
      min (total dose, 144 microg) sedation in a 3-yr-old child weighing 14 kg. The
      large dose of dexmedetomidine produced a hemodynamically stable patient who was
      deeply sedated for approximately 4 h after discontinuing the infusion.

PMID- 16790627
TI  - A comparison of the sedative, hemodynamic, and respiratory effects of
      dexmedetomidine and propofol in children undergoing magnetic resonance imaging.
AB  - We compared the sedative, hemodynamic, and respiratory effects of dexmedetomidine
      and propofol in children undergoing magnetic resonance imaging procedures. Sixty
      children were randomly distributed into two groups: The dexmedetomidine (D) group
      received 1 microg/kg initial dose followed by continuous infusion of 0.5
      microg.kg(-1).h(-1) and a propofol group (P) received 3 mg/kg initial dose
      followed by a continuous infusion of 100 microg.kg(-1).min(-1). Inadequate
      sedation was defined as difficulty in completing the procedure because of the
      child's movement during magnetic resonance imaging. Mean arterial pressure (MAP),
      heart rate, peripheral oxygen saturation, and respiratory rate (RR) were recorded
      during the study. The onset of sedation, recovery, and discharge time were
      significantly shorter in group P than in group D. MAP, heart rate, and RR
      decreased during sedation from the baseline values in both groups. MAP and RR
      were significantly lower in group P than in group D during sedation. Desaturation
      was observed in four children of group P. Dexmedetomidine and propofol provided
      adequate sedation in most of the children. We conclude that although propofol
      provided faster anesthetic induction and recovery times, it caused hypotension
      and desaturation. Thus, dexmedetomidine could be an alternative reliable sedative
      drug to propofol in selected patients.

PMID- 16790629
TI  - Recent smoking behavior and postoperative nausea and vomiting.
AB  - The risk of postoperative nausea and vomiting (PONV) is reduced in cigarette
      smokers by unknown mechanisms. If protection is related to an acute effect of
      smoke constituents, smokers with the most recent exposure to cigarette smoke
      would be most protected. We tested the hypothesis that in cigarette smokers,
      postoperative nausea is correlated with recent exposure to cigarette smoke as
      quantified by exhaled carbon monoxide (CO) concentrations. In this observational
      study, exhaled CO levels were measured in 140 female smokers preoperatively. PONV
      was assessed over the first 24 h after surgery. There was no correlation
      (assessed with Spearman rank correlation) between preoperative CO and nausea
      scores at recovery room discharge. Significant correlations were found between
      nausea assessed over the first 24 h postoperatively and a history of PONV or
      motion sickness, the use of intraoperative antiemetic prophylaxis, duration of
      anesthesia, and use of opioids in the postanesthesia care unit. However, there
      was no correlation between preoperative CO and nausea over the first 24 h. These
      preliminary data suggest that the effect of smoking in reduced PONV is not
      directly related to preoperative exhaled CO levels.

PMID- 16790630
TI  - Anesthetic considerations for magnetic seizure therapy: a novel therapy for
      severe depression.
AB  - Electroconvulsive therapy (ECT) is a highly effective treatment for severe
      depression. However, its use is associated with significant posttreatment
      cognitive impairment. Magnetic seizure therapy (MST) was developed as an
      alternative therapy that could reduce postseizure side effects through the
      induction of more "focal" seizure activity. Using an open-parallel study design,
      we compared 20 case-matched patients undergoing a series of either ECT or MST
      procedures with respect to their anesthetic, muscle relaxant, and cardiovascular
      drug requirements, effects on cardiovascular and electroencephalographic
      bispectral index (BIS) values, and early recovery times. We found that MST was
      associated with a reduced time to orientation (4 +/- 1 versus 18 +/- 5 min; P <
      0.01) compared with ECT. To minimize residual muscle paralysis after MST, a
      reduction in the succinylcholine dosage (38 +/- 17 versus 97 +/- 2 mg; P < 0.01)
      was required. The BIS values were higher before, and lower immediately after, the
      stimulus was applied in the MST (versus ECT) group. The Hamilton depression
      rating scale score was significantly reduced from the baseline value in both
      treatment groups; however, the posttreatment score was lower after the series of
      ECT treatments (6 +/- 6 versus 14 +/- 10; P < 0.05). We conclude that MST was
      associated with a decreased requirement for muscle relaxants, reduced variability
      in the BIS values after seizure induction, and a more rapid recovery of cognitive
      function compared with ECT. Further studies are required to evaluate the
      antidepressant efficacy of MST versus ECT when they are administered at
      comparable levels of cerebral stimulation.

PMID- 16790631
TI  - Chirality in anesthesia I: minimum alveolar concentration of secondary alcohol
      enantiomers.
AB  - Most studies of chirality in inhaled anesthetic action have used the enantiomers
      of isoflurane. These enantiomers are expensive and scarce, which limits studies,
      such as the preliminary identification of molecular targets of anesthetic action,
      that can be performed with these isomers. We hypothesized that secondary alcohols
      (i.e., compounds having a -CH2-CHOH-CH3 group) that are experimental anesthetics
      would show enantioselectivity. To test this hypothesis, we determined the minimum
      alveolar anesthetic concentration (MAC) of the enantiomers of the homologous
      series of 2-alcohols from 2-butanol to 2-heptanol in rats. Because these alcohols
      are partially metabolized to 2-ketones during the course of study (i.e., having a
      -CH2-CO-CH3 group), we independently measured the MAC of the 2-ketones. Assuming
      additivity of MAC of the ketones with the alcohols, we corrected for the
      anesthetic effect of the ketones in rats to determine the MAC of the alcohols. We
      found that the 2-butanol and 2-pentanol isomers were enantioselective. S-(+)-2
      butanol had a MAC that was 17% larger than for the R-(-)-enantiomer, whereas S
      (+)-2-pentanol had a MAC that was 38% larger than the R-(-)- enantiomer. No
      stereoselectivity was observed for 2-hexanol and 2-heptanol. These findings may
      permit studies of chirality in anesthesia, particularly in in vitro systems where
      metabolism does not occur, using inexpensive volatile compounds.

PMID- 16790633
TI  - Isoflurane decreases extracellular serotonin in the mouse hippocampus.
AB  - The serotonergic system may play a role during general anesthesia. Furthermore,
      alterations in serotonergic neurotransmission in the hippocampus have been linked
      to depression and anxiety as well as to changes in arousal and cognition. Little
      is known about the effects of volatile anesthetics on hippocampal serotonin (5
      HT) levels. In this study we examined the effects of isoflurane on hippocampal 5
      HT levels in mice. Adult male 129/SvEv mice were exposed to either isoflurane 1
      or 1.5 minimum alveolar concentration (MAC) both in 40% O2 in air or to 40% O2 in
      air alone (control) for a period of 80 min, and hippocampal 5-HT levels were
      measured by microdialysis coupled with high performance liquid chromatography.
      Within 20-40 min of administration, both doses of isoflurane similarly produced a
      significant decrease in hippocampal 5-HT to 41.5% +/- 11.0% and 36.4% +/- 13.9%
      of the baseline level in the isoflurane 1 MAC and 1.5 MAC groups, respectively.
      Furthermore, when additional dialysates were obtained on termination of
      anesthesia in the isoflurane 1.5 MAC group, the decrease in extracellular 5-HT
      levels persisted for several hours. To determine if isoflurane-induced changes in
      extracellular 5-HT involve the serotonin transporter (SERT), similar
      microdialysis studies were performed in C57BL/6 wild-type (SERT +/+) and
      homozygous SERT knockout (SERT -/-) mice exposed to either 1 MAC isoflurane in
      40% O2 in air or to 40% O2 in air alone for a period of 80 min. Isoflurane
      produced a significant decrease in hippocampal 5-HT in SERT +/+ and SERT -/-, and
      this decrease was larger in SERT -/- compared with SERT +/+: to 22.4% +/- 8.5%
      versus 50.2% +/- 17.4% of the baseline 5-HT level, respectively. These data
      suggest that isoflurane produces a decrease in hippocampal 5-HT, independent of
      SERT function.

PMID- 16790634
TI  - Chronic subarachnoid administration of 1-(4chlorobenzoyl)-5methoxy-2methyl-1H
      indole-3 acetic acid (indomethacin): an evaluation of its neurotoxic effects in
      an animal model.
AB  - Neuraxial administration of nonsteroid antiinflammatory drugs has been suggested
      as an alternative in the management of intractable pain, but there is little
      evidence that the neurotoxic effects of indomethacin by this route of
      administration have been evaluated. In this study, we evaluated histological
      neurotoxicity of indomethacin after its subarachnoid administration in guinea
      pigs. The hypothesis tested was "Does subarachnoid administration of indomethacin
      produce damage in the spinal cord of guinea pigs?" Ten male guinea pigs were
      anesthetized, and a polyamide catheter connected to a subcutaneous osmotic micro
      pump was implanted at the L2-3 level. Animals were randomly assigned in 2 groups
      of 5 animals each. Indomethacin or saline solution was administered by continuous
      infusion (0.5 microL/h) for 14 days. Neurotoxicity was determined by spinal cord
      histopathology. There was no evidence of toxicity in the histological
      examinations of either group. These data suggest that subarachnoid administration
      of indomethacin infusion, at these doses, did not produce lesions typical of
      neurotoxicity in the spinal cord. We have concluded that epidural administration
      of indomethacin may be considered an alternative for application in human pain
      management, although more studies to determine its safety are required.

PMID- 16790632
TI  - Chirality in anesthesia II: stereoselective modulation of ion channel function by
      secondary alcohol enantiomers.
AB  - Chirality has been proposed as a means for distinguishing relevant from
      irrelevant molecular targets of action, but the sensitivity and specificity of
      this test is unknown for volatile anesthetics. We applied enantiomers of two
      chiral anesthetic alcohols (2-butanol and 2-pentanol) that are enantioselective
      for the minimum alveolar concentration (MAC) preventing movement in 50% of
      animals and one (2-hexanol) that was not to frog oocytes. Each oocyte expressed
      one of three anesthetic-sensitive ion channels: a Twik-related-spinal cord K+
      (TRESK) channel, a gamma-amino butyric acid type A (GABA(A)) receptor and an N
      methyl-d-aspartate (NMDA) receptor. Using voltage-clamp techniques, we found that
      2-butanol was not enantioselective for any channel (e.g., 16 mM 2-butanol R(-)
      and S(-) enantiomers decreased current through an NMDA receptors by 44% +/- 3%
      [mean +/- se] and 37% +/- 4%, respectively); 2-pentanol was enantioselective for
      one channel (the GABA(A) receptor, the enantiomers increasing current by 277% +/-
      20% and 141% +/- 30%); 2-hexanol was enantioselective for both GABA(A) and NMDA
      receptors (e.g., decreasing current through the NMDA receptor by 19% +/- 3% and
      43% +/- 5%). We calculated the sensitivity and specificity of chirality as a test
      of anesthetic relevance under two scenarios: 1) all three channels were relevant
      mediators of MAC and 2) no channel was a mediator of MAC. These sensitivities and
      specificities were poor because there is no consistent correspondence between
      receptor and whole animal results. We recommend that enantioselectivity not be
      used as a test of relevance for inhaled anesthetic targets.

PMID- 16790635
TI  - Development of bronchoconstriction after administration of muscle relaxants in
      rabbits with normal or hyperreactive airways.
AB  - Neuromuscular blocking drugs can induce intraoperative bronchospasm. We
      characterized the magnitude and the temporal profile of the constriction in
      normal or in hyperresponsive airways after injections of neuromuscular blocking
      drugs. Respiratory system impedance (Zrs) was measured continuously over a 90-s
      apneic period in naive and rabbits sensitized to allergens by ovalbumin. Fifteen
      s after the start of Zrs recordings, succinylcholine, mivacurium, or pipecuronium
      was administered in random order. Zrs was then also recorded during the
      administration of increasing doses of exogenous histamine. To monitor the changes
      in the airway mechanics during these maneuvers, Zrs was averaged for 2-s time
      windows, and the airway resistance (Raw) was determined by model fitting. The
      increases in Raw were significantly larger in the sensitized rabbits than in the
      naive animals. The largest increases in Raw and the maximum rate of change in Raw
      were obtained for succinylcholine (146% +/- 29% and 0.80 +/- 0.12 cm H2O/L,
      respectively) and mivacurium (80% +/- 25% and 0.71 +/- 0.13 cm H2O/L) and the
      smallest were obtained for pipecuronium (40% +/- 12% and 0.41 +/- 0.04 cm H2O/L).
      Allergic sensitization leads to severe and rapidly developing bronchospasm after
      administrations of mivacurium or succinylcholine. These deleterious side effects
      should be considered when succinylcholine or mivacurium is administered in the
      presence of bronchial hyperreactivity.

PMID- 16790636
TI  - A small dose of hydrogen peroxide enhances tumor necrosis factor-alpha toxicity
      in inducing human vascular endothelial cell apoptosis: reversal with propofol.
AB  - We designed the present study to test the hypothesis that oxygen free radicals
      can enhance tumor necrosis factor (TNF)-alpha cellular toxicity, which might be
      reversed by propofol, an anesthetic with antioxidant properties, in human
      vascular endothelial cell line ECV304. Cultured ECV304 were either not treated,
      treated with 10 muM of hydrogen peroxide (H2O2), treated with TNF-alpha (40
      ng/mL) alone, TNF-alpha in the presence of 10 microM of H2O2 (H+T), or propofol
      plus H2O2 for 24 h. Cell viability was measured by lactate dehydrogenate (LDH)
      assay. Cell apoptosis was assessed by flow cytometry and terminal
      deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick
      end-labeling. The antiapoptotic Bcl-2 and pro-apoptotic Bax protein expressions
      were measured by immunocytochemical analysis. Increases in apoptosis, Bax, lipid
      peroxidation product malondialdehyde, LDH, and decreases in Bcl-2, superoxide
      dismutase, and glutathione peroxidase were observed in TNF-alpha-treated cells.
      H2O2 10 microM did not cause significant lipid peroxidation (0.75 +/- 0.03
      nmol/mg of malondialdehyde protein) as compared with control (0.70 +/- 0.04
      nmol/mg of malondialdehyde protein) (P > 0.05) but further enhanced TNF-alpha
      induced lipid peroxidation, upregulated Bax, and down-regulated Bcl-2 expression
      and enhanced TNF-alpha-induced cell apoptosis (P < 0.05). Propofol 50 microM
      attenuated TNF-alpha and H2O2-induced cell apoptosis, accompanied by decreases in
      malondialdehyde and LDH production and restoration of Bcl-2 expression. Propofol
      exerts protective effects against H2O2-enhanced TNF-alpha cell toxicity by
      reducing oxidative injury.

PMID- 16790638
TI  - Melatonin does not reduce anxiety more than placebo in the elderly undergoing
      surgery.
AB  - Melatonin has been reported to reduce preoperative anxiety. We performed this
      study to compare preoperative anxiety in elderly patients receiving melatonin (M)
      or placebo (P). Anxiety was measured in patients aged >65 yr by a numerical
      rating scale (range, 0-10). Each patient was randomized to receive M 10 mg or P
      orally: 71 patients were in group P and 67 in group M. The median (quartiles)
      anxiety level was 5 (2-8) before and 3 (1-7) 90 min after premedication in group
      M and 5 (3-6) and 3 (1-5) in group P, respectively. M and P reduce anxiety in
      elderly patients to a similar degree.

PMID- 16790637
TI  - Ethanol-induced hypnotic tolerance is absent in N-methyl-D-aspartate receptor
      epsilon 1 subunit knockout mice.
AB  - Recent pharmacological studies suggest that N-methyl-D-aspartate (NMDA) receptors
      play an important role in neuroadaptive processes in the development of tolerance
      to addictive drugs, such as opioids, amphetamine, and cocaine. In the present
      study, we investigated the contribution of the NMDA receptor to ethanol-induced
      hypnotic tolerance using NMDA receptor epsilon1 subunit knockout mice. Hypnotic
      sensitivity to a single injection of 3, 3.5, and 4 g/kg ethanol was not
      significantly different between wild-type mice and NMDA receptor epsilon1 subunit
      knockout mice. In contrast, although wild-type mice displayed hypnotic tolerance
      after repeated administration of 4 g/kg ethanol for 4 consecutive days, no change
      in the duration of hypnosis was observed in knockout mice. No significant
      differences were observed in blood ethanol clearance between wild-type and
      knockout mice on day 4. Our results indicate epsilon1 subunit containing the NMDA
      receptor might be involved in the development of ethanol-induced hypnotic
      tolerance.

PMID- 16790639
TI  - A surprising twist: an unusual failure of a keyed filling device specific for a
      volatile inhaled anesthetic.
AB  - We describe two cases in which keyed filling devices for sevoflurane were
      inadvertently screwed onto isoflurane bottles. The mishaps were possible because
      the collars on sevoflurane and isoflurane bottles are mirror images of each
      other. The particular keyed filling device was designed with a flexible outer
      sleeve and could be screwed onto the wrong bottle while slightly gouging its soft
      plastic collar. The keyed filling adapters for sevoflurane and isoflurane could
      each be manipulated to fit the other's bottle. A manufacturer (Southmedic, Inc.,
      Barrie, Canada) has modified their keyed filling adapters to prevent this unusual
      circumstance from recurring.

PMID- 16790640
TI  - An advanced specialty training program in anesthesiology: a special educational
      fellowship designed to return community anesthesiologists to clinical practice.
AB  - We describe a program for community anesthesiologists designed to evaluate
      clinical skills and provide additional training in the latest technologies in
      anesthesiology. This educational program was established for previously trained
      anesthesiologists who require additional training for either remedial purposes or
      because of a prolonged absence from practice. All enrollees had an active,
      unrestricted California medical license and malpractice insurance. Approximately
      half of the participants had been in active practice at the time of enrollment;
      the remainder had been away from practice from 1 to 9 yr. The first 24 graduates
      of the fellowship spent an average of 9 wk (range, 3-24 wk) in the program to
      meet their individualized goals. Graduates were surveyed an average of 15 mo
      after completion of the fellowship. All respondents indicated that they would
      enroll in the program again; 80% indicated they learned new technical skills, 73%
      stated that the fellowship introduced them to a greater variety of drugs, and 50%
      indicated that the fellowship changed their approach to patient care. This
      program may serve as a model for any discipline of medicine and is particularly
      relevant for those with a substantial component of technical skills expected of
      its practitioners.

PMID- 16790641
TI  - The medicolegal importance of enhancing timeliness of documentation when using an
      anesthesia information system and the response to automated feedback in an
      academic practice.
AB  - Documentation should ideally occur in real time immediately after completion of a
      service. Although electronic records often do not print the time that
      documentation notes were entered on the medical record, automated anesthesia
      record keeping systems store an audit trail that time stamps events entered by
      all anesthesia providers. As more lawyers become aware of this fact and
      requisition audit trails, prospective charting of necessary documentation may
      undermine the integrity of an anesthesia care team accused of malpractice, with
      potentially significant medicolegal consequences. We changed existing
      documentation practices of a large academic practice via a three-step process.
      Educational sessions increased the percentage of cases with correct timing of
      emergence documentation from 25% to 60% over a 2-mo period. Automated email
      performance feedback further increased correct note timing to 70%. When combined
      with personal contact by a member of the billing office and email copy
      notification of the chair, the percentage increased to >99.5%. The behavioral
      change was seen in all individuals, as 95% of attendings had < or = 2 records/mo
      with untimely documentation at the end of the study period. Once the habits were
      ingrained, further input was rarely necessary over the next 9 mo. This suggests
      physician behavioral change related to work process flow, unlike that related to
      patient care, is easily sustained.

PMID- 16790642
TI  - Attitudes of residents and anesthesiologists toward basic sciences.
AB  - The perceived relevance of the subject matter is an essential condition for adult
      learning. Attitudes refer to internal states that influence learner's choices of
      personal action, which determine the probability of learning behaviors. Our
      objectives in this study were to describe and compare attitudes of residents and
      anesthesiologists towards the relevance of basic sciences to clinical practice.
      An 8-item questionnaire was given to 105 residents and 142 anesthesiologists.
      Data were electronically collected. Responses were graded on 5-level Likert
      scales. Comparisons were made between responses of residents and
      anesthesiologists. Although a general pattern of acknowledged relevance of basic
      sciences to clinical practice was observed in both groups, anesthesiologists'
      ratings were significantly higher than residents' ratings. Both groups emphasized
      in-depth formal learning of basic sciences before their clinical application, but
      attending anesthesiologists' scores were significantly higher than residents'
      scores. Residents were more favorable to a more superficial approach represented
      by learning general concepts than anesthesiologists, although median scores were
      below the center of the scale (neutral). In both groups median ratings of the
      role of instructors in exciting residents' curiosity through the teaching of
      basic sciences were located in the center of the respective scales. Both groups
      rated their in-training educational experiences high.

PMID- 16790643
TI  - Hyperchloremic acidosis in the critically ill: one of the strong-ion acidoses?
AB  - Decreases in plasma bicarbonate are associated with hyperchloremic acidosis and
      lactic acidosis. According to the Stewart approach to acid-base physiology, the
      strong-ion difference regulates plasma bicarbonate, with chloride and lactate
      being the only strong anions routinely measured in clinical chemistry. We
      hypothesized that the plasma strong-ion difference, both with and without
      lactate, would have a stronger association with plasma bicarbonate than plasma
      chloride alone would have with bicarbonate. We used plasma acid-base data from
      300 critically ill patients. The correlation with bicarbonate became
      progressively weaker (P < 0.001): all measured strong ions, r = 0.60; measured
      strong ions without lactate, r = 0.42; chloride alone, r = -0.27. In a subgroup
      of 26 patients with traditional hyperchloremic acidosis (base excess < -2 mmol/L
      and anion gap <17 mmol/L), the measured strong-ion difference (without lactate)
      had a stronger correlation (P < 0.001) with bicarbonate than chloride had: r =
      0.85 versus r = -0.60. We conclude that hyperchloremic acidosis and lactic
      acidosis are strong-ion acidoses. Hyperchloremia should be viewed relative to the
      plasma strong cations. A practical conclusion is that both managing and
      preventing acid-base disorders with IV fluid therapy involves manipulating each
      of the plasma strong ions, particularly sodium and chloride.

PMID- 16790644
TI  - Hydroxyethyl starch exhibits antiinflammatory effects in the intestines of
      endotoxemic rats.
AB  - We performed the present in vivo study to investigate the effect of hydroxyethyl
      starch (HES) on intestinal production of inflammatory mediators and activation of
      transcription factors during endotoxemia. Rats with endotoxemia induced by
      lipopolysaccharide (LPS) (5 mg/kg, IV) were treated with HES (16 mL/kg, IV) or
      saline (64 mL/kg, IV). At 2, 3, or 6 h after the LPS challenge, the rat ileal
      tissues were collected. Various ileal inflammatory mediator levels (tumor
      necrosis factor-alpha, interleukin [IL]-6, cytokine-induced neutrophil
      chemoattractant-1, and IL-10), inflammatory mediator messenger RNAs (mRNAs),
      activities of nuclear factor (NF)-kappaB and activator protein (AP)-1, and ileal
      myeloperoxidase-positive cells were determined in each group. HES significantly
      reduced the increased intestinal levels of tumor necrosis factor-alpha, IL-6,
      cytokine-induced neutrophil chemoattractant-1, and the mRNAs in the endotoxemic
      rats. Similarly, HES could decrease the myeloperoxidase-positive cells induced by
      LPS and also inhibit ileal NF-kappaB and AP-1 activations. Our results suggest
      that during endotoxemia HES may down-regulate intestinal inflammatory mediator
      production, and this antiinflammatory effect of HES may act through suppression
      of NF-kappaB and AP-1 activations.

PMID- 16790645
TI  - Morphine sulfate attenuates hemorrhagic shock-induced hyperpermeability.
AB  - Morphine sulfate is often administered for patients requiring surgical
      intervention for the control of hemorrhage. Recent data implicate morphine as an
      immune modulator that affects white blood cells and increases infection rates. In
      addition, morphine releases histamine, an inflammatory mediator that increases
      microvascular permeability. Both of these actions of morphine could aggravate the
      inflammatory progress after hemorrhagic shock. In this study, we evaluated the
      role of morphine sulfate on microvascular permeability and its effects on
      leukocyte adherence after hemorrhagic shock. After a control period, blood was
      withdrawn to reduce the mean arterial blood pressure to 40 mm Hg for 1 h in
      urethane-anesthetized Sprague-Dawley rats. Mesenteric postcapillary venules in a
      transilluminated segment of small intestine were examined to quantify changes in
      permeability and leukocyte adherence. The rats received an IV injection of
      fluorescein isothiocyanate-bovine albumin during the control period. The
      fluorescent light intensity emitted from the fluorescein isothiocyanate-bovine
      albumin was recorded with digital microscopy within the lumen of the
      microvasculature and compared with the intensity of light in the extraluminal
      space over time. These images were downloaded to a computerized image analysis
      program that quantitates changes in light intensity. This change in light
      intensity represents albumin extravasation. In addition, bright-field images were
      recorded on compact disk for playback to determine leukocyte adherence.
      Leukocytes stationary for more than 30 s or longer in a 100-micron segment of
      venule was considered adherent. Our results demonstrated a marked increase in
      fluorescein isothiocyanate-bovine albumin leakage into the extravascular space
      after hemorrhagic shock. Hemorrhagic shock was also associated with an increase
      in leukocytes adhering to the postcapillary venular endothelium. Morphine sulfate
      10 microg/kg given before the shock period, attenuated both the hyperpermeability
      (P < 0.05) and the increase in leukocyte adherence (P < 0.05) after hemorrhagic
      shock. These results suggest that instead of aggravating the inflammatory
      response after hemorrhagic shock, morphine may provide protection to the
      microvasculature.

PMID- 16790646
TI  - Postoperative nausea and vomiting and pain after transsphenoidal surgery: a
      review of 877 patients.
AB  - Although postoperative nausea and vomiting and pain after supra- and
      infratentorial craniotomy have been evaluated in multiple studies, there are few
      data regarding pain or postoperative nausea and vomiting after transsphenoidal
      procedures. Therefore, we reviewed the perioperative records of 877 patients
      undergoing transsphenoidal surgery by the same surgeon. The overall incidence of
      postoperative emesis was 7.5%, significantly less than most studies of
      neurosurgical patients. An intraoperative cerebrospinal fluid leak and subsequent
      fat grafting, the use of lumbar intrathecal catheter, and patients presenting for
      the resection of a craniopharyngiomas all had a significantly increased incidence
      of postoperative emesis (11.4%, 17.1%, and 18%, respectively). Interestingly,
      antiemetic prophylaxis did not decrease the risk of vomiting overall or in any
      cohort of patients; however, both droperidol and ondansetron decreased the
      incidence of nausea in the postanesthesia care unit (PACU). Regarding pain and
      morphine consumption, patients who later developed diabetes insipidus had a
      significant increase in morphine requirements in the PACU. No other disease state
      was associated with increased pain or morphine consumption in the PACU.

PMID- 16790649
TI  - Induction of hypothermia after intraoperative hypoxic brain insult.
AB  - Hypoxic brain injury can be a devastating complication of anesthesia.
      Fortunately, it has become increasingly rare. Here we report a case of suspected
      intraoperative hypoxic brain injury treated with moderate hypothermia.
      Anesthesiologists should be aware of the option of using this therapy and how to
      employ it in the setting of suspected hypoxic brain injury.

PMID- 16790647
TI  - The comparative effects of sevoflurane versus isoflurane on cerebrovascular
      carbon dioxide reactivity in patients with diabetes mellitus.
AB  - The use of volatile anesthetics has been reported to alter cerebrovascular carbon
      dioxide (CO2) reactivity. We examined the comparative effects of sevoflurane
      versus isoflurane on cerebrovascular CO2 reactivity in 40 patients with diabetes
      mellitus. Anesthesia was maintained with either 1.0 minimum alveolar anesthetic
      concentration of sevoflurane or 1.0 minimum alveolar anesthetic concentration of
      isoflurane in 33% oxygen and 67% nitrous oxide. A 2.5-MHz pulsed transcranial
      Doppler probe was attached to the patient's head at the right temporal window for
      continuous measurement of mean blood flow velocity in the middle cerebral artery.
      After establishing baseline middle cerebral artery velocity values and
      cardiovascular hemodynamics, we increased end-tidal CO2 by decreasing ventilatory
      frequency by 2-5 breaths/min and repeated the measurements. These were then used
      to calculate absolute and relative CO2 reactivity. Absolute CO2 reactivity was
      less in insulin-treated patients with either sevoflurane or isoflurane compared
      with those patients on oral antidiabetic drugs or dietary therapy (sevoflurane
      group: diet = 2.6 +/- 0.6; oral antidiabetic drug = 2.5 +/- 0.8; insulin = 1.6 +/
      0.8*; isoflurane group: diet = 3.3 +/- i0.7; oral antidiabetic drug = 3.4 +/-
      0.7; insulin = 1.9 +/- 0.7* cm.s(-1).mm Hg(-1); *P < 0.05, respectively).
      Relative CO2 reactivity showed a similar pattern in the diet-controlled and oral
      antidiabetic groups, absolute and relative CO2 reactivities were lower with
      sevoflurane versus isoflurane. Hence, we conclude that cerebrovascular CO2
      reactivity in insulin-dependent patients is impaired under both sevoflurane and
      isoflurane anesthesia.

PMID- 16790648
TI  - The long-term effect of sevoflurane on neuronal cell damage and expression of
      apoptotic factors after cerebral ischemia and reperfusion in rats.
AB  - We investigated the long-term effects of sevoflurane on histopathologic injury
      and key proteins of apoptosis in a rat hemispheric ischemia/reperfusion model.
      Sixty-four male Sprague-Dawley rats were randomly assigned to Group 1 (fentanyl
      and N2O/O2; control) and Group 2 (2.0 vol% sevoflurane and O2/air). Ischemia (45
      min) was produced by unilateral common carotid artery occlusion plus hemorrhagic
      hypotension (mean arterial blood pressure 40 mm Hg). Animals were killed after 1,
      3, 7, and 28 days. In hematoxylin and eosin-stained brain sections eosinophilic
      hippocampal neurons were counted. Activated caspase-3 and the apoptosis
      regulating proteins Bax, Bcl-2, Mdm-2, and p53 were analyzed by immunostaining.
      No eosinophilic neurons were detected in sevoflurane-anesthetized rats over time,
      whereas 9%-38% of the hippocampal neurons were eosinophilic (days 1-28) in
      control animals. On days 1 and 3, the concentration of Bax was 140%-200% larger
      in fentanyl/N2O-anesthetized animals compared with sevoflurane. Bcl-2 was 100%
      less in control animals during the first 3 days. Activated caspase-3 was detected
      in neurons of both groups (0.75%-2.2%). These data support a sustained
      neuroprotective potency of sevoflurane related to reduced eosinophilic injury
      after cerebral ischemia/reperfusion.

PMID- 16790650
TI  - Levobupivacaine-sufentanil with or without epinephrine during epidural labor
      analgesia.
AB  - In a prospective, randomized, double-blind study, we investigated whether
      epinephrine increased the efficacy of levobupivacaine and sufentanil during
      epidural labor analgesia. Seventy term parturients received an epidural injection
      of levobupivacaine 0.125% and sufentanil 0.75 microg/mL with or without 1:800,000
      epinephrine. After an initial dose of 10 mL, a patient-controlled analgesia pump
      was started. Total and hourly drug consumption, pain scores using the visual
      analog scale, sensory and motor block, duration of labor, vital variables,
      maternal and neonatal outcome, and side effects were compared. If the parturients
      experienced insufficient pain relief during the study, even after a rescue dose
      of 10 mL, they were excluded from further study and received 10 mL of bupivacaine
      0.125% and sufentanil 0.75 microg/mL with 1:800,000 epinephrine. Hourly drug
      consumption, rescue dosing, and pain scores at 15 min and 20 min were lower in
      the epinephrine group. The incidence of motor block and duration of the second
      stage of labor tended to be higher in the epinephrine group and were associated
      with lower Apgar scores at 1 and 5 min. These findings suggest that the addition
      of epinephrine intensifies the effects of epidural levobupivacaine and sufentanil
      but may cause more motor block.

PMID- 16790652
TI  - The value of an albumin-based intravascular volume replacement strategy in
      elderly patients undergoing major abdominal surgery.
AB  - The value of human albumin (HA) for treating hypovolemia is controversial. Less
      expensive alternatives such as hydroxyethyl starch (HES) are sometimes refused
      because of unwanted side effects. We prospectively randomized 50 patients older
      than 70 years old undergoing major abdominal surgery to receive either 5% HA (n =
      25) or a third generation HES preparation (6% HES 130/0.4; n = 25) when mean
      arterial blood pressure was <60 mm Hg and central venous pressure was <10 mm Hg.
      Hemodynamics, inflammation (interleukin-6), endothelial activation-integrity
      (adhesion molecules), coagulation (thrombelastography), and renal function
      (including kidney-specific proteins) were monitored after the induction of
      anesthesia, after surgery, 5 h in the intensive care unit, and on the first
      postoperative day. HA patients received 3960 +/- 590 mL of HA and 5070 +/- 1030
      mL of Ringer's lactate solution, and HES patients received 3500 +/- 530 mL of HES
      and 4550 +/- 880 mL of Ringer's lactate solution. Total protein remained normal
      only in the HA-treated patients. No significant differences (P > 0.1) between the
      groups were seen with regard to hemodynamics, coagulation, and kidney function.
      Plasma levels of interleukin-6 and soluble adhesion molecules were significantly
      (P < 0.05) higher in the HA- than in the HES-treated patients. We conclude that
      HA in elderly patients undergoing major abdominal surgery can easily be replaced
      by a modern HES preparation. Because of the decreased inflammatory response and
      endothelial activation-injury, HES 130/0.4 seems to be the more appropriate fluid
      strategy for these patients.

PMID- 16790651
TI  - Combined spinal-epidural anesthesia for cesarean delivery: dose-dependent effects
      of hyperbaric bupivacaine on maternal hemodynamics.
AB  - Hypotension remains an important side effect of spinal anesthesia for cesarean
      delivery. There is limited evidence that reducing the spinal dose has a favorable
      effect on maternal hemodynamic stability. We designed the present randomized
      trial to test the hypothesis that reducing the spinal dose of local anesthetics
      results in equally effective anesthesia and less maternal hypotension. Fifty term
      pregnant patients were randomly assigned to two study groups. In the HIGH-group
      combined spinal-epidural anesthesia was performed using 9.5 mg hyperbaric
      bupivacaine combined with 2.5 microg sufentanil. In the LOW-group combined spinal
      epidural anesthesia was performed using 6.5 mg hyperbaric bupivacaine combined
      with 2.5 microg sufentanil. Demographic data, obstetrical data, visual analog
      scale score for pain, number of medical interventions for pain, maternal
      hemodynamics, and neonatal outcome were recorded. Patients in the HIGH-group
      experienced more pronounced and longer hypotensive periods as compared with the
      LOW-group. The mean lowest recorded systolic blood pressure was higher in the LOW
      group (102 +/- 16 versus 88 +/- 16 in the HIGH-group; P < 0.05). More patients in
      the HIGH-group experienced hypotension compared with the LOW-group (68% versus
      16%; P < 0.05). In the HIGH-group 15 patients required pharmacological treatment
      for hypotension compared with 5 in the LOW-group. Duration of effective
      anesthesia (block to cold sensation above or at T3) was longer in the HIGH-group
      as compared with the LOW-group (95 +/- 25 versus 68 +/- 18 min, respectively, P <
      0.05). We conclude that small-dose spinal anesthesia (6.5 mg hyperbaric
      bupivacaine combined with sufentanil) better preserves maternal hemodynamic
      stability with equally effective anesthesia that is of shorter duration.

PMID- 16790653
TI  - Laryngospasm after autologous blood transfusion.
AB  - Although perioperative autologous blood transfusions are associated with few side
      effects, transfusion reactions can occur and can be life-threatening. We report
      the occurrence of postoperative laryngospasm in a patient who underwent spinal
      anesthesia for hip surgery. The laryngospasm could not be attributed to any cause
      other than the autologous blood transfusion and recurred when the transfusion was
      restarted. Laryngospasm was successfully treated both times with positive
      pressure ventilation. Autologous transfusions can trigger febrile nonhemolytic
      transfusion reactions, which may result in airway compromise.

PMID- 16790654
TI  - General anesthesia and chronic amphetamine use: should the drug be stopped
      preoperatively?
AB  - Prescription amphetamines are being used more often for several medical
      conditions. Anesthesia concerns focus on the cardiovascular stability of patients
      who may be catecholamine-depleted and thus have a blunted response to
      intraoperative hypotension. Previously we reported one case of a patient
      receiving chronic amphetamine therapy who had a stable intraoperative course. We
      now report eight additional patients taking chronic prescription amphetamines who
      underwent a safe general anesthesia and outcome. Predominantly prescribed for
      narcolepsy and attention deficit hyperactivity disorder, amphetamine drugs had
      been given to these 8 patients for 2 to 10 yr. Ages ranged from 22 to 77 yr and
      genders were equally divided. All required general anesthesia for their surgical
      procedures and 6 of the 8 patients were tracheally intubated. Anesthesia
      operating room times ranged from 30 min to 4.25 h. The authors conclude that
      amphetamine use need not be stopped before surgery and anesthesia.

PMID- 16790655
TI  - Functional magnetic resonance imaging measures of the effects of morphine on
      central nervous system circuitry in opioid-naive healthy volunteers.
AB  - In this pilot study, we used functional magnetic resonance imaging (fMRI) to
      study the effects of morphine in 8 healthy, opioid-naive volunteers. Intravenous
      small-dose morphine (4 mg/70 kg) or saline was administered to volunteers
      undergoing a fMRI scan. Infusion of morphine, but not saline, elicited mild
      euphoria without aversive symptoms and resulted in positive signal changes in
      reward structures including the nucleus accumbens, sublenticular extended
      amygdala, orbitofrontal cortex, and hippocampus. The positive signal in the
      accumbens was opposite to the signal previously reported for noxious stimuli.
      Morphine produces a decreased signal in cortical areas in a similar manner to
      sedative-hypnotic drugs such as propofol or midazolam. Activation in endogenous
      analgesic regions was observed in the periaqueductal gray, the anterior cingulate
      gyrus (decreased signal), and hypothalamus (increased signals). The pattern of
      activation in reward circuitry was similar to that reported for euphoric drugs of
      abuse, providing a model to evaluate the initial effects of morphine on the
      central nervous system components of the circuitry involved in addiction. The
      segregation of fMRI response that was observed in cortical versus subcortical
      regions suggests a dissociation of reward from sensory-motor and cognitive
      functions. Activation patterns were opposite to those previously observed for the
      mu antagonist, naloxone.

PMID- 16790656
TI  - The efficacy of the non-opioid analgesics parecoxib, paracetamol and metamizol
      for postoperative pain relief after lumbar microdiscectomy.
AB  - In this prospective, double-blind, randomized, placebo-controlled study we
      compared the efficacy of three IV non-opioid analgesics for postoperative pain
      relief after lumbar microdiscectomy. Eighty healthy patients were randomly
      divided into 4 treatment groups (n = 20 each) to receive either parecoxib 40 mg,
      paracetamol 1 g, metamizol 1 g, or placebo IV 45 min before the end of surgery.
      In the postanesthesia care unit (PACU) patients were treated using patient
      controlled analgesia (PCA) with piritramide. In the metamizol group the pain
      score at arrival in the PACU was significantly lower compared with the
      paracetamol, parecoxib, and placebo groups. In addition, in the metamizol group
      significantly fewer patients required additional PCA compared with the other
      groups studied. However, in those patients who required additional pain therapy
      in the four treatment groups, there was no significant difference in time to
      first request for piritramide and cumulative consumption of piritramide as
      assessed by the PCA data in the PACU. The incidence of adverse side effects was
      infrequent in all groups. These results suggest that in patients undergoing
      lumbar microdiscectomy, metamizol is superior to parecoxib, paracetamol, and
      placebo for immediate postoperative pain relief with minimal side effects.

PMID- 16790657
TI  - Neuraxial anesthesia and analgesia in patients with preexisting central nervous
      system disorders.
AB  - Historically, the use of regional anesthetic techniques in patients with
      preexisting central nervous system (CNS) disorders has been considered relatively
      contraindicated. The fear of worsening neurologic outcome secondary to mechanical
      trauma, local anesthetic toxicity, or neural ischemia is commonly reported. We
      examined the frequency of new or progressive neurologic complications in patients
      with preexisting CNS disorders who subsequently underwent neuraxial blockade. The
      medical records of all patients at the Mayo Clinic from the period 1988 to 2000
      with a history of a CNS disorder who subsequently received neuraxial anesthesia
      or analgesia were retrospectively reviewed. One-hundred-thirty-nine (n = 139)
      patients were identified for study inclusion. Mean patient age was 60 +/- 17 yr.
      Gender distribution was 86 (62%) males and 53 (38%) females. An established CNS
      disorder diagnosis was present a mean of 23 +/- 23 yr at the time of surgical
      anesthesia, with 74 (53%) patients reporting active neurologic symptoms. Spinal
      anesthesia was performed in 75 (54%) patients, epidural anesthesia or analgesia
      in 58 (42%) patients, continuous spinal anesthesia in 4 (3%) patients, and a
      combined spinal-epidural technique in 2 (1%) patients. Bupivacaine was the local
      anesthetic most commonly used in all techniques. Epinephrine was added to the
      injectate in 72 (52%) patients. There were 15 (11%) technical complications, with
      the unintentional elicitation of a paresthesia and traumatic needle placement
      occurring most frequently. A satisfactory block was reported in 136 (98%)
      patients. No new or worsening postoperative neurologic deficits occurred when
      compared to preoperative findings (0.0%; 95% confidence interval, 0.0%-0.3%). We
      conclude that the risks commonly associated with neuraxial anesthesia and
      analgesia in patients with preexisting CNS disorders may not be as frequent as
      once thought and that neuraxial blockade should not be considered an absolute
      contraindication within this patient population.

PMID- 16790658
TI  - The feasibility and complications of the continuous popliteal nerve block: a 1001
      case survey.
AB  - Perineural catheters are increasingly used worldwide for the treatment of
      postoperative pain in orthopedics. Long-term complications associated with the
      placement of a perineural catheter remain largely unstudied. We investigated the
      efficacy and the acute and late complications associated with the continuous
      popliteal nerve block. One-thousand-one patients undergoing elective surgery of
      the ankle or foot and scheduled to have a continuous popliteal nerve block were
      prospectively evaluated. All patients received an initial bolus of 40 mL
      ropivacaine 0.5% through the catheter. A continuous infusion of ropivacaine 0.3%
      initiated 6 h after the initial bolus was administered for the first 24 h and
      then decreased to ropivacaine 0.2% until the end of the study period. The success
      rate and acute complications were recorded. The overall success rate was 97.5%.
      The highest success rate was associated with foot inversion. Acute complications
      consisted of paresthesias during nerve localization (0.5%), pain during local
      anesthetic application (0.8%), and blood aspiration (0.4%). No central nervous
      system toxicity or cardiotoxicity occurred. Late complications were checked at 10
      days and 3 mo after surgery. These included two cases of inflammation at the
      puncture site. No infection or neuropathy was observed. The use of continuous
      popliteal nerve block for ankle or foot surgery is associated with frequent
      success and few acute and late complications.

PMID- 16790659
TI  - Intrathecal 2-chloroprocaine for lower limb outpatient surgery: a prospective,
      randomized, double-blind, clinical evaluation.
AB  - We evaluated the dose-response relationship of 2-chloroprocaine for lower limb
      outpatient procedure in 45 ASA physical status I-II outpatients undergoing
      elective lower limb surgery under spinal anesthesia, with 30 mg (group Chlor-30,
      n = 15), 40 mg (group Chlor-40, n = 15), or 50 mg (group Chlor-50, n = 15) of 1%
      preservative free 2-chloroprocaine. Onset time was similar in the three groups.
      General anesthesia was never required to complete surgery. Intraoperative
      analgesic supplementation as a result of insufficient duration of spinal block
      was required in 5 patients of group Chlor-30 (35%) and 2 patients of group Chlor
      40 (13%) (P = 0.014), with a median (range) time for supplementation request of
      40 (30-60) min. Spinal block resolution and recovery of ambulation were faster in
      group Chlor-30 (60 [41-98] min and 85 [45-123] min) than in groups Chlor-40 (85
      [46-141] min and 180 [72-281] min) and Chlor-50 (97 [60-169] min and 185 [90-355]
      min) (P = 0.001 and P = 0.003, respectively), with no differences in home
      discharge time (182 [120-267] min in group Chlor-30, 198 [123-271] min in group
      Chlor-40, and 203 [102-394] min in group Chlor-50; P = 0.155). No transient
      neurologic symptoms were reported at 24-h and 7-day follow-up. We conclude that
      although 40 and 50 mg of 2-chloroprocaine provide adequate spinal anesthesia for
      outpatient procedures lasting 45-60 min, 30 mg produces a spinal block of
      insufficient duration.

PMID- 16790660
TI  - Peripheral flow index is a reliable and early indicator of regional block
      success.
AB  - We investigated the usefulness of peripheral flow index (PFI) measurement using a
      standard pulse oximetry digit probe for early prediction of successful regional
      blocks. Sixty-six patients scheduled for limb surgery underwent either axillary
      or sciatic block using a nerve stimulator technique with mepivacaine 1.5%. PFI,
      which is the ratio of the pulsatile versus the nonpulsatile component of the
      pulse oximetry signal, was recorded from 10 min before block insertion until 30
      min afterwards. PFI recordings of the unblocked limb were similarly recorded.
      Pinprick and cold sensation were assessed at 5-min intervals until 30 min after
      blockade. An increase in PFI by a factor of 1.55 at 10 min after axillary block
      placement (P = 0.006), and 12 min after sciatic block placement (P = 0.001) was
      required to predict a successful block. The sensitivity and specificity of PFI
      was 100% for predicting axillary block outcomes at this time. Positive predictive
      value was 95% and negative predictive value was 93%. For sciatic blocks,
      sensitivity and specificity were 90% and 100%, respectively. The calculated
      positive predictive value at time 12 min for sciatic blocks was 94% and negative
      predictive value was 92%. At 15 min after block placement, cold and pinprick
      sensations had the same calculated values for sensitivity and specificity at 71%
      and 100%, respectively, for axillary blocks. For sciatic blocks, cold sensation
      had a sensitivity of 77% and a specificity of 100%, whereas pinprick had a
      sensitivity of just 20% with a specificity of 100%. We conclude that PFI provides
      a simple, early, and objective assessment of the success and failure of nerve
      blocks.

PMID- 16790661
TI  - A prospective, randomized comparison between the popliteal and subgluteal
      approaches for continuous sciatic nerve block with stimulating catheters.
AB  - In this prospective, blinded study, we randomized 56 patients undergoing hallux
      valgus repair to receive continuous sciatic nerve block using a subgluteal (n =
      28) or a posterior popliteal approach (n = 28) with a perineural stimulating
      catheter. Postoperatively, the stimulating catheter was connected to a patient
      controlled analgesia pump with 0.0625% levobupivacaine (basal infusion rate of 3
      mL/h, patient-controlled bolus dose of 3 mL, and lockout time of 20 min). Both
      approaches provided similar postoperative analgesia; however, local anesthetic
      consumption was larger in the popliteal group (4.9 +/- 1.4 mL/h) compared with
      the subgluteal group (3.8 +/- 1.1 mL/h; P < 0.05). We conclude continuous
      postoperative analgesia using stimulating catheters was effective at both
      injection sites; however, a subgluteal approach reduced the overall amount of
      local anesthetic.

PMID- 16790663
TI  - Untying the Gordian knot.

PMID- 16790664
TI  - The use of "off-label" drugs.

PMID- 16790665
TI  - Preliminary experience with dexmedetomidine in pediatric anesthesia.

PMID- 16790666
TI  - What good are large databases of intraoperative data?

PMID- 16790667
TI  - Mandibular nerve block for the removal of dentures during trismus caused by
      tetanus.

PMID- 16790668
TI  - Rocuronium in emergent intubation.

PMID- 16790669
TI  - Electromagnetic emission of high-energy extracorporeal shockwave lithotripsy to
      the shoulder does not cause disruption of bispectral index monitoring of propofol
      or sevoflurane anesthesia.

PMID- 16790670
TI  - Tube design for nasotracheal intubation.

PMID- 16790671
TI  - Total intravenous anesthesia with propofol and remifentanil for video-assisted
      thoracoscopic thymectomy in patients with myasthenia gravis.

PMID- 16790672
TI  - A useful modification of the Bier's block.

PMID- 16790673
TI  - Anesthesia for a patient with tracheal tumor using laryngeal mask airway.

PMID- 16790674
TI  - Spinal, but not epidural anesthesia, for pubic symphysis separation.

PMID- 16790675
TI  - Unexpected falsely low pulse oximeter measurements in a child with hemoglobin
      Cheverly.

PMID- 16790676
TI  - Failure to advance a guidewire during internal jugular venous cannulation: an
      unusual cause.

PMID- 16790677
TI  - Intrathecal therapy-associated masses.

PMID- 16790678
TI  - Hemodynamics with propofol: is propofol dangerous in classes III-V patients?

PMID- 16790679
TI  - Anticoagulation management for patients with drug-eluting stents undergoing
      vascular surgery.

PMID- 16790680
TI  - The use of vasopressin bolus to treat refractory hypotension secondary to
      reperfusion during orthotopic liver transplantation.

PMID- 16790681
TI  - A model of postanesthesia care unit-based acute pain service.

PMID- 16790682
TI  - Gabapentin for the treatment of refractory dysesthetic pain after open
      cholecystectomy.

PMID- 16790683
TI  - Angulation of the airway tube in the AMBU laryngeal mask could be responsible for
      improved insertion success.

PMID- 16790684
TI  - Heart rate variability as a promising tool to predict hypotension.

PMID- 16790685
TI  - Adenylate kinases 1 and 2 are part of the accessory structures in the mouse sperm
      flagellum.
AB  - Proper sperm function depends on adequate ATP levels. In the mammalian flagellum,
      ATP is generated in the midpiece by oxidative respiration and in the principal
      piece by glycolysis. In locations where ATP is rapidly utilized or produced,
      adenylate kinases (AKs) maintain a constant adenylate energy charge by
      interconverting stoichiometric amounts of ATP and AMP with two ADP molecules. We
      previously identified adenylate kinase 1 and 2 (AK1 and AK2) by mass spectrometry
      as part of a mouse SDS-insoluble flagellar preparation containing the accessory
      structures (fibrous sheath, outer dense fibers, and mitochondrial sheath). A germ
      cell-specific cDNA encoding AK1 was characterized and found to contain a
      truncated 3' UTR and a different 5' UTR compared to the somatic Ak1 mRNA;
      however, it encoded an identical protein. Ak1 mRNA was upregulated during late
      spermiogenesis, a time when the flagellum is being assembled. AK1 was first seen
      in condensing spermatids and was associated with the outer microtubular doublets
      and outer dense fibers of sperm. This localization would allow the
      interconversion of ATP and ADP between the fibrous sheath where ATP is produced
      by glycolysis and the axonemal dynein ATPases where ATP is consumed. Ak2 mRNA was
      expressed at relatively low levels throughout spermatogenesis, and the protein
      was localized to the mitochondrial sheath in the sperm midpiece. AK1 and AK2 in
      the flagellar accessory structures provide a mechanism to buffer the adenylate
      energy charge for sperm motility.

PMID- 16790686
TI  - Bovine seminal plasma proteins PDC-109, BSP-A3, and BSP-30-kDa share functional
      roles in storing sperm in the oviduct.
AB  - On ejaculation, sperm become coated with proteins secreted by the male accessory
      sex glands. In the bull, these proteins consist predominantly of the bovine
      seminal plasma family of proteins (BSPs): PDC-109 (BSP-A1/-A2), BSP-A3, and BSP
      30-kDa. PDC-109 plays a role in forming an oviductal sperm reservoir by enabling
      sperm to bind to oviductal epithelium. Because PDC-109 has high sequence identity
      with the other BSPs, we tested BSP-A3 and BSP-30-kDa for the capacity to bind
      sperm to oviductal epithelium. BSP-A3 and BSP-30-kDa each increased binding of
      epididymal sperm to epithelium and were as effective as PDC-109 in competitively
      inhibiting binding of ejaculated sperm. Because binding extends the motile life
      of sperm, BSPs were tested for the ability to maintain sperm motility. BSP
      treated epididymal sperm incubated with plasma membrane vesicles from bovine
      oviductal epithelium maintained progressive motility longer than untreated sperm.
      To our knowledge, this is the first report of this protective effect of BSPs.
      Similarities in function among the BSPs were reflected in their three-dimensional
      structure, whereas surface maps of electrostatic potential indicated differences
      in binding affinities and kinetics. Such differences may provide sperm with
      greater adaptability to variations among females. Altogether, these results
      indicate that BSPs play a crucial role in fertilization by maintaining sperm
      motility during storage.

PMID- 16790687
TI  - Ontogeny of tyrosine phosphorylation-signaling pathways during spermatogenesis
      and epididymal maturation in the mouse.
AB  - The objectives of this study were to map the ontogeny of tyrosine phosphorylation
      signal transduction pathways during germ cell development and to determine their
      association with the differentiation of a functional gamete. Until testicular
      germ cells differentiate into spermatozoa, cAMP-induced tyrosine phosphorylation
      is not detectable. Entry of these cells into the epididymis is accompanied by
      sudden activation of the tyrosine phosphorylation pathway, initially in the
      principal piece of the cell and subsequently in the midpiece. In the caput and
      corpus epididymides, the potential to express this pathway is inhibited by the
      presence of calcium in the extracellular medium. However, calcium has no effect
      on the expression of this pathway in caudal epididymal sperm. The competence of
      these cells to phosphorylate the entire sperm tail, from the neck to the tail-end
      piece, is accompanied by a capacity to exhibit hyperactivated motility on
      stimulation with cAMP. A distinctly different pattern of tyrosine
      phosphorylation, involving the acrosomal domain of the sperm head, is invoked as
      spermatozoa enter the caput epididymis, and phosphorylation remains high until
      these cells enter the distal corpus and cauda. The proportion of cells exhibiting
      this form of tyrosine phosphorylation is not affected by extracellular calcium or
      cAMP but is negatively correlated (R2 = 0.99) with their ability to acrosome
      react. However, this relationship is not causative. Our findings indicate that
      the development of functional spermatozoa is accompanied by carefully
      orchestrated changes in tyrosine phosphorylation, controlled by independent
      regulatory mechanisms in distinct subcellular compartments of these highly
      specialized cells.

PMID- 16790688
TI  - Bovine SNRPN methylation imprint in oocytes and day 17 in vitro-produced and
      somatic cell nuclear transfer embryos.
AB  - Findings from recent studies have suggested that the low survival rate of animals
      derived via somatic cell nuclear transfer (SCNT) may be in part due to epigenetic
      abnormalities brought about by this procedure. DNA methylation is an epigenetic
      modification of DNA that is implicated in the regulation of imprinted genes.
      Genes subject to genomic imprinting are expressed monoallelically in a parent of
      origin-dependent manner and are important for embryo growth, placental function,
      and neurobehavioral processes. The vast majority of imprinted genes have been
      studied in mice and humans. Herein, our objectives were to characterize the
      bovine SNRPN gene in gametes and to compare its methylation profile in in vivo
      produced, in vitro-produced, and SCNT-derived Day 17 elongating embryos. A CpG
      island within the 5' region of SNRPN was identified and examined using bisulfite
      sequencing. SNRPN alleles were unmethylated in sperm, methylated in oocytes, and
      approximately 50% methylated in somatic samples. The examined SNRPN region
      appeared for the most part to be normally methylated in three in vivo-produced
      Day 17 embryos and in eight in vitro-produced Day 17 embryos examined, while
      alleles from Day 17 SCNT embryos were severely hypomethylated in seven of eight
      embryos. In this study, we showed that the SNRPN methylation profiles previously
      observed in mouse and human studies are also conserved in cattle. Moreover, SCNT
      derived Day 17 elongating embryos were abnormally hypomethylated compared with in
      vivo-produced and in vitro-produced embryos, which in turn suggests that SCNT may
      lead to faulty reprogramming or maintenance of methylation imprints at this
      locus.

PMID- 16790689
TI  - KIT/KIT ligand in mammalian oogenesis and folliculogenesis: roles in rabbit and
      murine ovarian follicle activation and oocyte growth.
AB  - In rodent ovaries Kit ligand (KITL) and its receptor KIT have diverse roles,
      including the promotion of primordial follicle activation, oocyte growth, and
      follicle survival. Studies were undertaken to determine whether KITL and KIT
      carry out similar activities in rabbits. KitlandKitmRNA and protein were
      localized to oocytes and granulosa cells, respectively, in the rabbit ovary.
      Ovarian cortical explants from juvenile rabbits and neonatal mouse ovaries were
      subsequently cultured with recombinant mouse KITL and/or KITL neutralizing
      antibody. Indices of follicle growth initiation were compared with controls and
      between treatment groups for each species. Recombinant mouse KITL had no
      stimulatory effect on primordial follicle recruitment in cultured rabbit ovarian
      explants. However, the mean diameter of oocytes from primordial, early primary,
      primary, and growing primary follicles increased significantly in recombinant
      mouse KITL-treated explants compared with untreated tissues. In contrast,
      recombinant mouse KITL promoted both primordial follicle activation and an
      increase in the diameter of oocytes from primordial and early primary follicles
      in the mouse, and these effects were inhibited by coculture with KITL
      neutralizing antibody. Recombinant mouse KITL had no effect on follicle survival
      for either species. These data demonstrate that KITL promotes the growth of
      rabbit and mouse oocytes and stimulates primordial follicle activation in the
      mouse but not in the rabbit. We propose that the physiologic roles of KITL and
      KIT may differ between species, and this has important implications for the
      design of in vitro culture systems for folliculogenesis in mammals, including the
      human.

PMID- 16790690
TI  - C-reactive protein in vulnerable coronary plaques.
AB  - BACKGROUND: An increased level of serum C-reactive protein (CRP) is a known
      prognostic factor for acute coronary events and sudden cardiac death, and it is
      associated with coronary calcification. CRP is expressed in coronary arteries,
      but its role in the development of coronary plaques is unclear. AIM: To
      investigate CRP immunoreactivity in relation to the severity of coronary artery
      disease and plaque morphology in human left anterior descending coronary arteries
      (LAD). METHODS: A prospective, consecutive autopsy series of 66 patients (mean
      age 63.4 years) in Tampere University Hospital, Tampere, Finland. RESULTS: CRP
      immunoreactivity was seen in 59% of the cases. In logistic regression analysis
      with age, sex and body mass index as confounders, CRP immunoreactivity in LAD was
      associated with >50% stenosis and plaque calcification. All three cases with
      acute coronary thrombosis due to rupture or erosion of the plaque showed a clear
      immunopositive reaction. CRP-positive cells were never detected in normal
      arteries, but were often found in early fibrous plaques (75%) and almost
      invariably present in the shoulder area of plaques with necrotic core (96%). CRP
      immunoreactivity adjacent to calcified areas in more stable plaques (71%) was
      less consistent with one-third of these plaques showing no immunoreactivity.
      CONCLUSIONS: CRP immunoreactivity is associated with the progression of
      atherosclerosis, and especially with unstable coronary plaques. The
      immunoreactivity could cease at the stable calcified stages of atherosclerosis.

PMID- 16790691
TI  - Biological and prognostic role of acid cysteine proteinase inhibitor (ACPI,
      cystatin A) in non-small-cell lung cancer.
AB  - BACKGROUND: Acid cysteine protease inhibitor (ACPI) is an intracellular protein,
      often linked to neoplastic changes in epithelium and thought to have an
      inhibitory role in malignant transformation. AIM: To analyse the expression and
      prognostic role of ACPI in non-small-cell lung cancer (NSCLC). METHOD:
      Histological samples from 199 patients with resected NSCLC were stained
      immunohistochemically for the expression of ACPI in normal and preneoplastic
      bronchial epithelium, and in various types of lung carcinomas. RESULTS: A normal
      bronchial epithelium showed positive staining for ACPI in the basal cells,
      whereas the upper two-thirds of the dysplastic epithelium was ACPI positive. High
      staining for ACPI was found in 74% (91/123) of squamous-cell carcinomas, whereas
      16% (8/49) of adenocarcinomas and 30% of (8/27) large-cell carcinomas showed the
      high expression of ACPI (p<0.001). Among squamous-cell carcinomas, low expression
      of ACPI was correlated with poor tumour differentiation (p=0.032). In the whole
      tissue, reduced expression of ACPI was associated with tumour recurrence
      (p=0.024). In overall survival (OS) and disease-free survival (DFS) analyses, the
      histological type of the tumour (both p<0.001) and stage of the tumour (p=0.001,
      p=0.013, respectively) were related to patient outcome. Low expression of ACPI in
      tumour cells was associated with poor OS and DFS (p<0.041, p=0.004,
      respectively). In multivariate analysis, ACPI did not retain its prognostic
      value, whereas the traditional factors were the most important prognostic
      factors. CONCLUSIONS: ACPI expression is linked with the malignant transformation
      of the bronchial epithelium and predicts a risk of tumour recurrence as well as
      poor rate of survival for the patients. However, ACPI does not have any
      independent prognostic value in NSCLC.

PMID- 16790692
TI  - Angiogenesis in nodal B cell lymphomas: a high throughput study.
AB  - AIM: To assess the biological significance of vascular endothelial growth factor
      (VEGF) A, VEGF receptor (Flk-1) and cyclooxygenase 2 (COX2) expression with
      respect to microvessel density (MVD), proliferative activity (Ki-67), expression
      of p53 and clinical presentation in a large cohort of nodal B cell lymphomas.
      METHODS: An immunohistochemical and morphometric study was performed on a
      validated tissue microarray containing 271 B cell lymphoma specimens, 197 of
      which included follow-up data. Statistical assessment was done by Pearson's
      chi(2) test, Spearman's rank correlation coefficient, analysis of variance and
      survival analysis. RESULTS: 266 (98%) cases were evaluable. Strong VEGF
      expression was observed in only 20 diffuse large B cell lymphomas (DLBCLs). Flk-1
      and COX2 were expressed in 53 and 21 cases, respectively, mainly in DLBCLs,
      follicular lymphoma (FL) grade 3 and mantle cell lymphomas (MCLs), in a low
      proportion of cells. MVD decreased in the following order: DLBCLs, FLs, MCLs and
      small lymphocytic lymphomas/chronic lymphocytic leukaemia (SLL/CLLs). VEGF
      expression correlated with Ki-67, p53 and COX2 expression in the whole cohort and
      in DLBCLs. Flk-1 expression correlated with Ki-67 in the cohort and in SLL/CLL
      and FL grade 1 and 2. COX2 expression correlated with Ki-67 and p53. The analysed
      angiogenesis parameters did not correlate with clinical parameters or survival.
      CONCLUSIONS: Angiogenesis plays a differential role in various B cell lymphomas.
      Aggressive lymphomas express the potential molecular therapeutic targets VEGF and
      COX2, and have higher MVD. In a few low proliferation-fraction lymphomas, Flk-1
      might have a role in proliferative advantage. Therapeutic strategies aimed at
      angiogenesis should take into account lymphoma heterogeneity.

PMID- 16790694
TI  - Images in clinical medicine. Venous air embolism.

PMID- 16790693
TI  - Chromosome 6p amplification and cancer progression.
AB  - Chromosomal imbalances represent an important mechanism in cancer progression. A
      clear association between DNA copy-number aberrations and prognosis has been
      found in a variety of tumours. Comparative genomic hybridisation studies have
      detected copy-number increases affecting chromosome 6p in several types of
      cancer. A systematic analysis of large tumour cohorts is required to identify
      genomic imbalances of 6p that correlate with a distinct clinical feature of
      disease progression. Recent findings suggest that a central part of the short arm
      of chromosome 6p harbours one or more oncogenes directly involved in tumour
      progression. Gains at 6p have been associated with advanced or metastatic
      disease, poor prognosis, venous invasion in bladder, colorectal, ovarian and
      hepatocellular carcinomas. Copy number gains of 6p DNA have been described in a
      series of patients who presented initially with follicle centre lymphoma, which
      subsequently transformed to diffuse large B cell lymphoma. Melanoma cytogenetics
      has consistently identified aberrations of chromosome 6, and a correlation with
      lower overall survival has been described. Most of the changes observed in
      tumours to date map to the 6p21-p23 region, which encompasses approximately half
      of the genes on all of chromosome 6 and one third of the number of CpG islands in
      this chromosome. Analyses of the genes that cluster to the commonly amplified
      regions of chromosome 6p have helped to identify a small number of molecular
      pathways that become deregulated during tumour progression in diverse tumour
      types. Such pathways offer promise for new treatments in the future.

PMID- 16790695
TI  - ADHD in adults.

PMID- 16790696
TI  - Condoms and sexually-transmitted infections.

PMID- 16790697
TI  - Condom use and the risk of genital human papillomavirus infection in young women.
AB  - BACKGROUND: To evaluate whether the use of male condoms reduces the risk of male
      to-female transmission of human papillomavirus (HPV) infection, longitudinal
      studies explicitly designed to evaluate the temporal relationship between condom
      use and HPV infection are needed. METHODS: We followed 82 female university
      students who reported their first intercourse with a male partner either during
      the study period or within two weeks before enrollment. Cervical and vulvovaginal
      samples for HPV DNA testing and Papanicolaou testing were collected at
      gynecologic examinations every four months. Every two weeks, women used
      electronic diaries to record information about their daily sexual behavior. Cox
      proportional-hazards models were used to evaluate risk factors for HPV infection.
      RESULTS: The incidence of genital HPV infection was 37.8 per 100 patient-years at
      risk among women whose partners used condoms for all instances of intercourse
      during the eight months before testing, as compared with 89.3 per 100 patient
      years at risk in women whose partners used condoms less than 5 percent of the
      time (adjusted hazard ratio, 0.3; 95 percent confidence interval, 0.1 to 0.6,
      adjusted for the number of new partners and the number of previous partners of
      the male partner). Similar associations were observed when the analysis was
      restricted to high-risk and low-risk types of HPV and HPV types 6, 11, 16, and
      18. In women reporting 100 percent condom use by their partners, no cervical
      squamous intraepithelial lesions were detected in 32 patient-years at risk,
      whereas 14 incident lesions were detected during 97 patient-years at risk among
      women whose partners did not use condoms or used them less consistently.
      CONCLUSIONS: Among newly sexually active women, consistent condom use by their
      partners appears to reduce the risk of cervical and vulvovaginal HPV infection.

PMID- 16790698
TI  - Cyclophosphamide versus placebo in scleroderma lung disease.
AB  - BACKGROUND: We conducted a double-blind, randomized, placebo-controlled trial to
      determine the effects of oral cyclophosphamide on lung function and health
      related symptoms in patients with evidence of active alveolitis and scleroderma
      related interstitial lung disease. METHODS: At 13 clinical centers throughout the
      United States, we enrolled 158 patients with scleroderma, restrictive lung
      physiology, dyspnea, and evidence of inflammatory interstitial lung disease on
      examination of bronchoalveolar-lavage fluid, thoracic high-resolution computed
      tomography, or both. Patients received oral cyclophosphamide (< or =2 mg per
      kilogram of body weight per day) or matching placebo for one year and were
      followed for an additional year. Pulmonary function was assessed every three
      months during the first year, and the primary end point was the forced vital
      capacity (FVC, expressed as a percentage of the predicted value) at 12 months,
      after adjustment for the baseline FVC. RESULTS: Of 158 patients, 145 completed at
      least six months of treatment and were included in the analysis. The mean
      absolute difference in adjusted 12-month FVC percent predicted between the
      cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence
      interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were
      also treatment-related differences in physiological and symptom outcomes, and the
      difference in FVC was maintained at 24 months. There was a greater frequency of
      adverse events in the cyclophosphamide group, but the difference between the two
      groups in the number of serious adverse events was not significant. CONCLUSIONS:
      One year of oral cyclophosphamide in patients with symptomatic scleroderma
      related interstitial lung disease had a significant but modest beneficial effect
      on lung function, dyspnea, thickening of the skin, and the health-related quality
      of life. The effects on lung function were maintained through the 24 months of
      the study.

PMID- 16790699
TI  - Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis.
AB  - BACKGROUND: Systemic sclerosis (scleroderma) is characterized by immunologic
      abnormalities, injury of endothelial cells, and tissue fibrosis. Abnormal
      oxidative stress has been documented in scleroderma and linked to fibroblast
      activation. Since platelet-derived growth factor (PDGF) stimulates the production
      of reactive oxygen species (ROS) and since IgG from patients with scleroderma
      reacts with human fibroblasts, we tested the hypothesis that patients with
      scleroderma have serum autoantibodies that stimulate the PDGF receptor (PDGFR),
      activating collagen-gene expression. METHODS: We analyzed serum from 46 patients
      with scleroderma and 75 controls, including patients with other autoimmune
      diseases, for stimulatory autoantibodies to PDGFR by measuring the production of
      ROS produced by the incubation of purified IgG with mouse-embryo fibroblasts
      carrying inactive copies of PDGFR alpha or beta chains or the same cells
      expressing PDGFR alpha or beta. Generation of ROS was assayed with and without
      specific PDGFR inhibitors. Antibodies were characterized by immunoprecipitation,
      immunoblotting, and absorption experiments. RESULTS: Stimulatory antibodies to
      the PDGFR were found in all the patients with scleroderma. The antibodies
      recognized native PDGFR, inducing tyrosine phosphorylation and ROS accumulation.
      Autoantibody activity was abolished by preincubation with cells expressing the
      PDGFR alpha chain or with recombinant PDGFR or by PDGFR tyrosine kinase
      inhibitors. Stimulatory PDGFR antibodies selectively induced the Ha-Ras-ERK1/2
      and ROS cascades and stimulated type I collagen-gene expression and myofibroblast
      phenotype conversion in normal human primary fibroblasts. CONCLUSIONS:
      Stimulatory autoantibodies against PDGFR appear to be a specific hallmark of
      scleroderma. Their biologic activity on fibroblasts strongly suggests that they
      have a causal role in the pathogenesis of the disease.

PMID- 16790700
TI  - Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common type of cardiac arrhythmia and
      a leading cause of cardiovascular morbidity, particularly stroke. The cardiac gap
      junction protein connexin 40 is expressed selectively in atrial myocytes and
      mediates the coordinated electrical activation of the atria. We hypothesized that
      idiopathic atrial fibrillation has a genetic basis and that tissue-specific
      mutations in GJA5, the gene encoding connexin 40, may predispose the atria to
      fibrillation. METHODS: We sequenced GJA5 from genomic DNA isolated from resected
      cardiac tissue and peripheral lymphocytes from 15 patients with idiopathic atrial
      fibrillation. Identified GJA5 mutations were transfected into a gap-junction
      deficient cell line to assess their functional effects on protein transport and
      intercellular electrical coupling. RESULTS: Four novel heterozygous missense
      mutations were identified in 4 of the 15 patients. In three patients, the
      mutations were found in the cardiac-tissue specimens but not in the lymphocytes,
      indicating a somatic source of the genetic defects. In the fourth patient, the
      sequence variant was detected in both cardiac tissue and lymphocytes, suggesting
      a germ-line origin. Analysis of the expression of mutant proteins revealed
      impaired intracellular transport or reduced intercellular electrical coupling.
      CONCLUSIONS: Mutations in GJA5 may predispose patients to idiopathic atrial
      fibrillation by impairing gap-junction assembly or electrical coupling. Our data
      suggest that common diseases traditionally considered to be idiopathic may have a
      genetic basis, with mutations confined to the diseased tissue.

PMID- 16790702
TI  - Images in clinical medicine. Acquired hypertrichosis lanuginosa.

PMID- 16790701
TI  - Omalizumab for asthma.

PMID- 16790703
TI  - Case records of the Massachusetts General Hospital. Case 19-2006. A 22-month-old
      boy with the rapid growth of subcutaneous nodules.

PMID- 16790705
TI  - Cyclophosphamide for scleroderma lung disease.

PMID- 16790706
TI  - Autoantibodies against PDGF receptor in scleroderma.

PMID- 16790707
TI  - Connexins, conduction, and atrial fibrillation.

PMID- 16790708
TI  - Bioterror and "bioart"--a plague o' both your houses.

PMID- 16790709
TI  - Transforming growth factor beta signaling, vascular remodeling, and hypertension.

PMID- 16790710
TI  - An inactivated subvirion influenza A (H5N1) vaccine.

PMID- 16790711
TI  - Gatifloxacin and dysglycemia in older adults.

PMID- 16790712
TI  - Pregnancy in recipients of solid-organ transplants.

PMID- 16790713
TI  - Case 7-2006: a man with altered mental status and acute renal failure.

PMID- 16790714
TI  - Clinical and genetic characteristics of patients with neurofibromatosis type 1
      and pheochromocytoma.

PMID- 16790715
TI  - Fatal infection with influenza A (H5N1) virus in China.

PMID- 16790716
TI  - Don't ignore vitamin D.

PMID- 16790717
TI  - Improving children's medicines.

PMID- 16790718
TI  - Falling necropsy rates and risks to public health.

PMID- 16790719
TI  - Intraoral graphite tattoo.

PMID- 16790720
TI  - Schonlein-Henoch purpura involving the penis.

PMID- 16790721
TI  - Survival probability in ataxia telangiectasia.
AB  - Ataxia telangiectasia is a rare, multiorgan neurodegenerative disorder with
      enhanced vulnerability to cancer and infection. Median survival in two large
      cohorts of patients with this disease, one prospective and one retrospective, is
      25 and 19 years, with a wide range. Life expectancy does not correlate well with
      severity of neurological impairment.

PMID- 16790722
TI  - Measuring body composition.
AB  - Several aspects of body composition, in particular the amount and distribution of
      body fat and the amount and composition of lean mass, are now understood to be
      important health outcomes in infants and children. Their measurement is
      increasingly considered in clinical practice; however, paediatricians are often
      unsure as to which techniques are appropriate and suitable for application in
      specific contexts. This article summarises the pros and cons of measurement
      technologies currently available for paediatric application. Simple techniques
      are adequate for many purposes, and simple regional data may often be of greater
      value than "whole body" values obtained by more sophisticated approaches.

PMID- 16790723
TI  - Respiratory health and baby swimming.

PMID- 16790724
TI  - Detection and follow up of infants at risk of congenital syphilis.

PMID- 16790725
TI  - MMR Catch up Campaign: reasons for refusal to consent.

PMID- 16790726
TI  - This could be due to maternal testosterone...

PMID- 16790727
TI  - Rebound bilirubin: on what should the decision to recommence phototherapy be
      based?

PMID- 16790728
TI  - How effectively can clinical examination pick up congenital heart disease at
      birth?

PMID- 16790729
TI  - Death in the neonatal intensive care unit: changing patterns of end of life care
      over two decades.
AB  - BACKGROUND: Death remains a common event in the neonatal intensive care unit, and
      often involves limitation or withdrawal of life sustaining treatment. OBJECTIVE:
      To document changes in the causes of death and its management over the last two
      decades. METHODS: An audit of infants dying in the neonatal intensive care unit
      was performed during two epochs (1985-1987 and 1999-2001). The principal
      diagnoses of infants who died were recorded, as well as their apparent prognoses,
      and any decisions to limit or withdraw medical treatment. RESULTS: In epoch 1,
      132 infants died out of 1362 admissions (9.7%), and in epoch 2 there were 111
      deaths out of 1776 admissions (6.2%; p<0.001). Approximately three quarters of
      infants died after withdrawal of life sustaining treatment in both epochs. There
      was a significant reduction in the proportion of deaths from chromosomal
      abnormalities, and from neural tube defects in epoch 2. CONCLUSIONS: There have
      been substantial changes in the illnesses leading to death in the neonatal
      intensive care unit. These may reflect the combined effects of prenatal diagnosis
      and changing community and medical attitudes.

PMID- 16790730
TI  - Congenital depression of the neonatal skull: a self limiting condition.

PMID- 16790731
TI  - Spontaneous knot formation impeding the removal of a silicone urethral catheter.

PMID- 16790732
TI  - Freeze-thawing of breast milk does not prevent cytomegalovirus transmission to a
      preterm infant.
AB  - Freezing human milk is recommended to inactivate cytomegalovirus (CMV). A case of
      a preterm infant exclusively receiving frozen breast milk from his CMV
      seropositive mother showed that storage of breast milk for two months at -20
      degrees C did not prevent symptomatic postnatal CMV infection.

PMID- 16790733
TI  - Determination of the prevalence of drug misuse by meconium analysis.
AB  - In a pilot study to determine the local prevalence of maternal drug misuse,
      meconium from 400 infants was analysed for metabolites of eight controlled drugs.
      Cannabinoids were found in 13.25%, cocaine in 2.75%, and amphetamine in 1.75%.
      The prevalence of opiate and benzodiazepine misuse was masked by the presence of
      prescribed drugs so was undeterminable.

PMID- 16790734
TI  - Preterm mortality and morbidity over 25 years.
AB  - Changing preterm population variables have masked improvements in neonatal
      survival over time. Increased use of antenatal steroids, caesarean section, and
      surfactant may have reduced the likelihood of mortality and periventricular
      haemorrhage by a third and doubled that of chronic lung disease, persistent duct,
      and septicaemia.

PMID- 16790735
TI  - Are carbon dioxide detectors useful in neonates?
AB  - Maintenance of neonatal normocarbia may prevent chronic lung disease and
      periventricular leucomalacia, but this requires frequent arterial sampling, which
      has risks. Alternative methods for measuring CO2 are therefore desirable. These
      include end tidal CO2, capillary sampling, and transcutaneous measurements. CO2
      detectors have also proved effective and rapid indicators of endotracheal
      intubation. However, this method relies on the presence of exhaled CO2, which may
      be reduced in certain situations, such as cardiopulmonary arrest. Colorimetric
      CO2 detectors are therefore valuable adjuncts for airway management, especially
      during resuscitation, but Pa(CO2) is still the best measure of CO2 in neonatal
      practice.

PMID- 16790736
TI  - The late effects of fetal growth patterns.
AB  - The immediate prenatal and postnatal consequences of reduced fetal growth have
      long been known. The longer term associations between reduced birth weight and
      adult disease risk are also now well established. Reduced fetal growth is usually
      detected late in gestation, and the assumption has been that this is the time
      when factors regulating fetal growth have their greatest effect. However, recent
      evidence suggests that both the growth trajectory of the fetus and its adaptive
      responses to the prenatal and postnatal environment may be determined in the
      period around the time of conception.

PMID- 16790737
TI  - The future of neonatal therapeutic trials.
AB  - Neonatology has undoubtedly benefited from clinical trials. Nevertheless, more
      treatments based on inadequate experimental evidence are given than those that
      are supported by a validated evidence base. Clinicians seeking the basis for
      their current and future clinical practice are faced with challenges in the
      shadow of recent UK legislation and government recommendations. All patients must
      be protected from inappropriate research, but the benefits of regulations must be
      appropriately balanced with those of properly conducted clinical trials. It is
      ethically difficult both to persist with treatments of unproven benefit and
      unknown harm and to deny infants potentially valuable therapies. It is important
      that trials are conducted within the new legislative framework, but their future
      may rest with innovative solutions and the determination of all involved in the
      process.

PMID- 16790738
TI  - Sir Frederic Still (1868-1941): the father of British paediatrics.
AB  - As a pioneer of full time paediatrics, as the first professor in this new
      discipline, and as inaugural president of the British Paediatric Association,
      Still has been called with justice the father of British paediatrics.

PMID- 16790739
TI  - Unexpected course of left leg percutaneous silastic catheters.

PMID- 16790740
TI  - Neonatal long lines: localisation with conventional radiography using a
      horizontal beam technique.

PMID- 16790741
TI  - Guilt by association: the nuclear envelope proteome and disease.
AB  - The discovery that many inherited diseases are linked to interacting nuclear
      envelope proteins has raised the possibility that human genetic studies could be
      assisted by a fusion with proteomics. Two principles could be applied. In the
      first, the proteome of an organelle associated with a genetically variable
      disease is determined. The chromosomal locations of the genes encoding the
      organellar proteins are then determined. If a related disease is linked to a
      large chromosomal region that includes a gene identified in the organelle, then
      that gene has an increased likelihood of causing the disease. Directly sequencing
      this allele from patient samples might speed identification compared with further
      genetic linkage studies as has been demonstrated for multiple diseases associated
      with the nuclear envelope. The second principle is that if an organelle has been
      implicated in the pathology of a particular disorder, then comparison of the
      organelle proteome from control and patient cells might highlight differences
      that could indicate the causative protein. The distinct, tissue-specific
      pathologies associated with nuclear envelope diseases suggest that many tissues
      will have a set of disorders linked to this organelle, and there are numerous as
      yet unmapped or partially mapped syndromes that could benefit from such an
      approach.

PMID- 16790743
TI  - Oxidized ATP protection against anthrax lethal toxin.
AB  - Bacillus anthracis lethal toxin (LT) induces rapid lysis (<90 min) of murine
      macrophages from certain inbred strains. The mechanism for LT-induced cytolysis
      is currently unknown. We hypothesized that the ATP-activated macrophage P2X7
      receptors implicated in nucleotide-mediated macrophage lysis could play a role in
      LT-mediated cytolysis and discovered that a potent P2X7 antagonist, oxidized ATP
      (o-ATP), protects macrophages against LT. Other P2X7 receptor antagonists,
      however, had no effect on LT function, while oxidized nucleotides, o-ADP, o-GTP,
      and o-ITP, which did not act as receptor ligands, provided protection. Cleavage
      of the LT substrates, the mitogen-activated protein kinases, was inhibited by o
      ATP in RAW274.6 macrophages and CHO cells. We investigated the various steps in
      the intoxication pathway and found that binding of the protective-antigen (PA)
      component of LT to cells and the enzymatic proteolytic ability of the lethal
      factor (LF) component of LT were unaffected by o-ATP. Instead, the drug inhibited
      formation of the sodium dodecyl sulfate-resistant PA oligomer, which occurs in
      acidified endosomes, but did not prevent cell surface PA oligomerization, as
      evidenced by binding and translocation of LF to a protease-resistant
      intracellular location. We found that o-ATP also protected cells from anthrax
      edema toxin and diphtheria toxin, which also require an acidic environment for
      escape from endosomes. Confocal microscopy using pH-sensitive fluorescent dyes
      showed that o-ATP increased endosomal pH. Finally, BALB/cJ mice injected with o
      ATP and LT were completely protected against lethality.

PMID- 16790742
TI  - Stress wars: the direct role of host and bacterial molecular chaperones in
      bacterial infection.

PMID- 16790744
TI  - Intrastrain heterogeneity of the mgpB gene in Mycoplasma genitalium is extensive
      in vitro and in vivo and suggests that variation is generated via recombination
      with repetitive chromosomal sequences.
AB  - Mycoplasma genitalium is associated with reproductive tract disease in women and
      may persist in the lower genital tract for months, potentially increasing the
      risk of upper tract infection and transmission to uninfected partners. Despite
      its exceptionally small genome (580 kb), approximately 4% is composed of repeated
      elements known as MgPar sequences (MgPa repeats) based on their homology to the
      mgpB gene that encodes the immunodominant MgPa adhesin protein. The presence of
      these MgPar sequences, as well as mgpB variability between M. genitalium strains,
      suggests that mgpB and MgPar sequences recombine to produce variant MgPa
      proteins. To examine the extent and generation of diversity within single strains
      of the organism, we examined mgpB variation within M. genitalium strain G-37 and
      observed sequence heterogeneity that could be explained by recombination between
      the mgpB expression site and putative donor MgPar sequences. Similarly, we
      analyzed mgpB sequences from cervical specimens from a persistently infected
      woman (21 months) and identified 17 different mgpB variants within a single
      infecting M. genitalium strain, confirming that mgpB heterogeneity occurs over
      the course of a natural infection. These observations support the hypothesis that
      recombination occurs between the mgpB gene and MgPar sequences and that the
      resulting antigenically distinct MgPa variants may contribute to immune evasion
      and persistence of infection.

PMID- 16790745
TI  - Characterization of phagosome trafficking and identification of PhoP-regulated
      genes important for survival of Yersinia pestis in macrophages.
AB  - The transcriptional activator PhoP is important for survival of Yersinia pestis
      in macrophage phagosomes. However, the phagosomes inhabited by Y. pestis have not
      been well characterized, and the mechanism by which PhoP promotes bacterial
      survival in these vacuoles is not fully understood. Lysosomal tracers, as well as
      antibodies to late endosomal or lysosomal proteins, were used in conjunction with
      confocal or electron microscopy to study the trafficking of phagosomes containing
      phoP(+) or phoP mutant Y. pestis strains or latex beads in J774A.1 macrophages.
      Phagosomes containing phoP(+) or phoP mutant Y. pestis acquired lysosomal markers
      to the same degree that phagosomes containing latex beads acquired these markers
      after 1.5 h of infection, showing that nascent phagosomes containing Y. pestis
      fuse with lysosomes irrespective of the phoP genotype. Similar results were
      obtained when phagosomes containing viable or dead phoP(+) Y. pestis cells or
      beads were analyzed at 8 h postinfection, indicating that the Y. pestis vacuole
      does not become secluded from the lysosomal compartment. However, only viable
      phoP(+) bacteria induced the formation of spacious phagosomes at 8 h
      postinfection, suggesting that Y. pestis can actively direct the expansion of its
      vacuole. PhoP-regulated genes that are important for survival of Y. pestis in
      phagosomes were identified by Tn5-lacZ mutagenesis and oligonucleotide microarray
      analysis. Three such genes were identified, and the products of these genes are
      predicted to promote resistance to antimicrobial peptides (ugd and pmrK) or low
      Mg(2+) conditions (mgtC) found in phagosomes. Viable count assays carried out
      with Y. pestis ugd, mgtC, and ugd mgtC mutants revealed that the products of ugd
      and mgtC function independently to promote early survival of Y. pestis in
      macrophage phagosomes.

PMID- 16790746
TI  - Molecular and functional characterization of a ToxR-regulated lipoprotein from a
      clinical isolate of Aeromonas hydrophila.
AB  - Human diseases caused by species of Aeromonas have been classified into two major
      groups: septicemia and gastroenteritis. In this study, we reported the molecular
      and functional characterization of a new virulence factor, ToxR-regulated
      lipoprotein, or TagA, from a diarrheal isolate, SSU, of Aeromonas hydrophila. The
      tagA gene of A. hydrophila exhibited 60% identity with that of a recently
      identified stcE gene from Escherichia coli O157:H7, which encoded a protein
      (StcE) that provided serum resistance to the bacterium and prevented erythrocyte
      lysis by controlling classical pathway of complement activation by cleaving the
      complement C1-esterase inhibitor (C1-INH). We purified A. hydrophila TagA as a
      histidine-tagged fusion protein (rTagA) from E. coli DE3 strain using a T7
      promoter-based pET30 expression vector and nickel affinity column chromatography.
      rTagA cleaved C1-INH in a time-dependent manner. The tagA isogenic mutant of A.
      hydrophila, unlike its corresponding wild-type (WT) or the complemented strain,
      was unable to cleave C1-INH, which is required to potentiate the C1-INH-mediated
      lysis of host and bacterial cells. We indeed demonstrated colocalization of C1
      INH and TagA on the bacterial surface by confocal fluorescence microscopy, which
      ultimately resulted in increased serum resistance of the WT bacterium. Likewise,
      we delineated the role of TagA in contributing to the enhanced ability of C1-INH
      to inhibit the classical complement-mediated lysis of erythrocytes. Importantly,
      we provided evidence that the tagA mutant was significantly less virulent in a
      mouse model of infection (60%) than the WT bacterium at two 50% lethal doses,
      which resulted in 100% mortality within 48 h. Taken together, our data provided
      new information on the role of TagA as a virulence factor in bacterial
      pathogenesis. This is the first report of TagA characterization from any species
      of Aeromonas.

PMID- 16790747
TI  - Bacillus anthracis phospholipases C facilitate macrophage-associated growth and
      contribute to virulence in a murine model of inhalation anthrax.
AB  - Several models of anthrax pathogenesis suggest that early in the infectious
      process Bacillus anthracis endospores germinate and outgrow into vegetative
      bacilli within phagocytes before being released into the blood. Here, we define
      the respective contributions of three phospholipases C (PLCs) to the pathogenesis
      of B. anthracis. Genetic deletions of the PLCs were made in the Sterne 7702
      background, resulting in the respective loss of their activities. The PLCs were
      redundant both in tissue culture and in murine models of anthrax. Deletion of all
      three PLC genes was required for attenuation of virulence in mice after
      intratracheal inoculation. This attenuation may be attributed to the inability of
      the PLC-null strain to grow in association with the macrophage. Complementation
      of these defects in both models of anthrax was achieved by expression of the PLC
      genes in trans. The functional redundancy between PLCs in the virulence of B.
      anthracis implies that their activities are important for anthrax pathogenesis.

PMID- 16790748
TI  - Escherichia coli cytotoxic necrotizing factor 1 blocks cell cycle G2/M transition
      in uroepithelial cells.
AB  - Evidence is accumulating that a growing number of bacterial toxins act by
      modulating the eukaryotic cell cycle machinery. In this context, we provide
      evidence that a protein toxin named cytotoxic necrotizing factor 1 (CNF1) from
      uropathogenic Escherichia coli is able to block cell cycle G(2)/M transition in
      the uroepithelial cell line T24. CNF1 permanently activates the small GTP-binding
      proteins of the Rho family that, beside controlling the actin cytoskeleton
      organization, also play a pivotal role in a large number of other cellular
      processes, including cell cycle regulation. The results reported here show that
      CNF1 is able to induce the accumulation of cells in the G(2)/M phase by
      sequestering cyclin B1 in the cytoplasm and down-regulating its expression. The
      possible role played by the Rho GTPases in the toxin-induced cell cycle
      deregulation has been investigated and discussed. The activity of CNF1 on cell
      cycle progression can offer a novel view of E. coli pathogenicity.

PMID- 16790749
TI  - Invasion of epithelial cells and proteolysis of cellular focal adhesion
      components by distinct types of Porphyromonas gingivalis fimbriae.
AB  - Porphyromonas gingivalis fimbriae are classified into six types (types I to V and
      Ib) based on the fimA genes encoding FimA (a subunit of fimbriae), and they play
      a critical role in bacterial interactions with host tissues. In this study, we
      compared the efficiencies of P. gingivalis strains with distinct types of
      fimbriae for invasion of epithelial cells and for degradation of cellular focal
      adhesion components, paxillin, and focal adhesion kinase (FAK). Six
      representative strains with the different types of fimbriae were tested, and P.
      gingivalis with type II fimbriae (type II P. gingivalis) adhered to and invaded
      epithelial cells at significantly greater levels than the other strains. There
      were negligible differences in gingipain activities among the six strains;
      however, type II P. gingivalis apparently degraded intracellular paxillin in
      association with a loss of phosphorylation 30 min after infection. Degradation
      was blocked with cytochalasin D or in mutants with fimA disrupted. Paxillin was
      degraded by the mutant with Lys-gingipain disrupted, and this degradation was
      prevented by inhibition of Arg-gingipain activity by Nalpha-p-tosyl-l-lysine
      chloromethyl ketone. FAK was also degraded by type II P. gingivalis. Cellular
      focal adhesions with green fluorescent protein-paxillin macroaggregates were
      clearly destroyed, and this was associated with cellular morphological changes
      and microtubule disassembly. In an in vitro wound closure assay, type II P.
      gingivalis significantly inhibited cellular migration and proliferation compared
      to the cellular migration and proliferation observed with the other types. These
      results suggest that type II P. gingivalis efficiently invades epithelial cells
      and degrades focal adhesion components with Arg-gingipain, which results in
      cellular impairment during wound healing and periodontal tissue regeneration.

PMID- 16790750
TI  - Cell wall-mediated neuronal damage in early sepsis.
AB  - Neuronal dysfunction can occur in the course of sepsis without meningitis. Sepsis
      associated neuronal damage (SAND) was observed in the hippocampus within hours in
      experimental pneumococcal bacteremia. Intravascular challenge with purified
      bacterial cell wall recapitulated SAND. SAND persisted in PAFr(-/-) mice but was
      partially mitigated in mice lacking cell wall recognition proteins TLR2 and Nod2
      and in mice overexpressing interleukin-10 (IL-10) in macrophages. Thus, cell wall
      drives SAND through IL-10-repressible inflammatory events. Treatment with CDP
      choline ameliorated SAND, suggesting that it may be an effective adjunctive
      therapy to increase survival and reduce organ damage in sepsis.

PMID- 16790751
TI  - Early events in Mycobacterium tuberculosis infection in cynomolgus macaques.
AB  - Little is known regarding the early events of infection of humans with
      Mycobacterium tuberculosis. The cynomolgus macaque is a useful model of
      tuberculosis, with strong similarities to human tuberculosis. In this study,
      eight cynomolgus macaques were infected bronchoscopically with low-dose M.
      tuberculosis; clinical, immunologic, microbiologic, and pathologic events were
      assessed 3 to 6 weeks postinfection. Gross pathological abnormalities were
      observed as early as 3 weeks, including Ghon complex formation by 5 weeks
      postinfection. Caseous granulomas were observed in the lung as early as 4 weeks
      postinfection. Only caseous granulomas were observed in the lungs at these early
      time points, reflecting a rigorous initial response. T-cell activation (CD29 and
      CD69) and chemokine receptor (CXCR3 and CCR5) expression appeared localized to
      different anatomic sites. Activation markers were increased on cells from airways
      and only at modest levels on cells in peripheral blood. The priming of
      mycobacterium-specific T cells, characterized by the production of gamma
      interferon occurred slowly, with responses seen only after 4 weeks of infection.
      These responses were observed from T lymphocytes in blood, airways, and hilar
      lymph node, with responses predominantly localized to the site of infection. From
      these studies, we conclude that immune responses to M. tuberculosis are
      relatively slow in the local and peripheral compartments and that necrosis occurs
      surprisingly quickly during granuloma formation.

PMID- 16790752
TI  - Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to
      form a biofilm on catheter surfaces through an ethanol-based mechanism.
AB  - Candida biofilms formed on indwelling medical devices are increasingly associated
      with severe infections. In this study, we used proteomics and Western and
      Northern blotting analyses to demonstrate that alcohol dehydrogenase (ADH) is
      downregulated in Candida biofilms. Disruption of ADH1 significantly (P = 0.0046)
      enhanced the ability of Candida albicans to form biofilm. Confocal scanning laser
      microscopy showed that the adh1 mutant formed thicker biofilm than the parent
      strain (210 microm and 140 microm, respectively). These observations were
      extended to an engineered human oral mucosa and an in vivo rat model of catheter
      associated biofilm. Inhibition of Candida ADH enzyme using disulfiram and 4
      methylpyrazole resulted in thicker biofilm (P < 0.05). Moreover, biofilms formed
      by the adh1 mutant strain produced significantly smaller amounts of ethanol, but
      larger amounts of acetaldehyde, than biofilms formed by the parent and revertant
      strains (P < 0.0001), demonstrating that the effect of Adh1p on biofilm formation
      is mediated by its enzymatic activity. Furthermore, we found that 10% ethanol
      significantly inhibited biofilm formation in vitro, with complete inhibition of
      biofilm formation at ethanol concentrations of >/=20%. Similarly, using a
      clinically relevant rabbit model of catheter-associated biofilm, we found that
      ethanol treatment inhibited biofilm formation by C. albicans in vivo (P < 0.05)
      but not by Staphylococcus spp. (P > 0.05), indicating that ethanol specifically
      inhibits Candida biofilm formation. Taken together, our studies revealed that
      Adh1p contributes to the ability of C. albicans to form biofilms in vitro and in
      vivo and that the protein restricts biofilm formation through an ethanol
      dependent mechanism. These results are clinically relevant and may suggest novel
      antibiofilm treatment strategies.

PMID- 16790754
TI  - Identification of novel virulence determinants in Mycobacterium paratuberculosis
      by screening a library of insertional mutants.
AB  - Johne's disease, caused by Mycobacterium paratuberculosis infection, is a
      worldwide problem for the dairy industry and has a possible involvement in
      Crohn's disease in humans. To identify virulence determinants of this
      economically important pathogen, a library of 5,060 transposon mutants was
      constructed using Tn5367 insertion mutagenesis, followed by large-scale
      sequencing to identify disrupted genes. In this report, 1,150 mutants were
      analyzed and 970 unique insertion sites were identified. Sequence analysis of the
      disrupted genes indicated that the insertion of Tn5367 was more prevalent in
      genomic regions with G+C content (50.5 to 60.5%) lower than the average G+C
      content (69.3%) of the rest of the genome. Phenotypic screening of the library
      identified disruptions of genes involved in iron, tryptophan, or mycolic acid
      metabolic pathways that displayed unique growth characteristics. Bioinformatic
      analysis of disrupted genes identified a list of potential virulence determinants
      for further testing with animals. Mouse infection studies showed a significant
      decrease in tissue colonization by mutants with a disruption in the gcpE, pstA,
      kdpC, papA2, impA, umaA1, or fabG2_2 gene. Attenuation phenotypes were tissue
      specific (e.g., for the umaA1 mutant) as well as time specific (e.g., for the
      impA mutant), suggesting that those genes may be involved in different virulence
      mechanisms. The identified potential virulence determinants represent novel
      functional classes that could be necessary for mycobacterial survival during
      infection and could provide suitable targets for vaccine and drug development
      against Johne's and Crohn's diseases.

PMID- 16790753
TI  - In vivo role of dendritic cells in a murine model of pulmonary cryptococcosis.
AB  - Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus
      neoformans in vitro and are believed to be important for inducing protective
      immunity against this organism. Exposure to C. neoformans occurs mainly by
      inhalation, and in this study we examined the in vivo interactions of C.
      neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat
      killed C. neoformans were administered intranasally to C57BL/6 mice. At specific
      times postinoculation, mice were sacrificed, and lungs were removed. Single-cell
      suspensions of lung cells were prepared, stained, and analyzed by microscopy and
      flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans
      had been internalized by DC, macrophages, and neutrophils in the mouse lung.
      Additionally, lung DC from mice infected for 7 days showed increased expression
      of the maturation markers CD80, CD86, and major histocompatibility complex class
      II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus
      specific T cells resulted in increased interleukin-2 production compared to the
      production by DC from naive mice, suggesting that there was antigen-specific T
      cell activation. This study demonstrated that DC in the lung are capable of
      phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans
      specific T cells ex vivo, suggesting that these cells have roles in innate and
      adaptive pulmonary defenses against cryptococcosis.

PMID- 16790755
TI  - LuxS involvement in the regulation of genes coding for hemin and iron acquisition
      systems in Porphyromonas gingivalis.
AB  - The periodontal pathogen Porphyromonas gingivalis employs a variety of mechanisms
      for the uptake of hemin and inorganic iron. Previous work demonstrated that hemin
      uptake in P. gingivalis may be controlled by LuxS-mediated signaling. In the
      present study, the expression of genes involved in hemin and iron uptake was
      determined in parent and luxS mutant strains by quantitative real-time reverse
      transcription-PCR. Compared to the parental strain, the luxS mutant showed
      reduced levels of transcription of genes coding for the TonB-linked hemin binding
      protein Tlr and the lysine-specific protease Kgp, which can degrade host heme
      containing proteins. In contrast, there was up-regulation of the genes for
      another TonB-linked hemin binding protein, HmuR; a hemin binding lipoprotein,
      FetB; a Fe(2+) ion transport protein, FeoB1; and the iron storage protein
      ferritin. Differential expression of these genes in the luxS mutant was maximal
      in early-exponential phase, which corresponded with peak expression of luxS and
      AI-2 signal activity. Complementation of the luxS mutation with wild-type luxS in
      trans rescued expression of hmuR. Mutation of the GppX two-component signal
      transduction pathway caused an increase in expression of luxS along with tlr and
      lower levels of message for hmuR. Moreover, expression of hmuR was repressed, and
      expression of tlr stimulated, when the luxS mutant was incubated with AI-2
      partially purified from the culture supernatant of wild-type cells. A phenotypic
      outcome of the altered expression of genes involved in hemin uptake was
      impairment of growth of the luxS mutant in hemin-depleted medium. The results
      demonstrate a role of LuxS/AI-2 in the regulation of hemin and iron acquisition
      pathways in P. gingivalis and reveal a novel control pathway for luxS expression.

PMID- 16790756
TI  - The novel Helicobacter pylori CznABC metal efflux pump is required for cadmium,
      zinc, and nickel resistance, urease modulation, and gastric colonization.
AB  - Maintaining metal homeostasis is crucial for the adaptation of Helicobacter
      pylori to the gastric environment. Iron, copper, and nickel homeostasis has
      recently been demonstrated to be required for the establishment of H. pylori
      infection in animal models. Here we demonstrate that the HP0969-0971 gene cluster
      encoding the Czc-type metal export pump homologs HP0969, HP0970, and the H.
      pylori-specific protein HP0971 forms part of a novel H. pylori metal resistance
      determinant, which is required for gastric colonization and for the modulation of
      urease activity. Insertional mutagenesis of the HP0971, HP0970, or HP0969 genes
      in H. pylori reference strain 26695 resulted in increased sensitivity to cadmium,
      zinc, and nickel (czn), suggesting that the encoded proteins constitute a metal
      specific export pump. Accordingly, the genes were designated cznC (HP0971), cznB
      (HP0970), and cznA (HP0969). The CznC and CznA proteins play a predominant role
      in nickel homeostasis, since only the cznC and cznA mutants but not the cznB
      mutant displayed an 8- to 10-fold increase in urease activity. Nickel-specific
      affinity chromatography demonstrated that recombinant versions of CznC and CznB
      can bind to nickel and that the purified CznB protein interacted with cadmium and
      zinc, since both metals competitively inhibited nickel binding. Finally, single
      cznA, cznB, and cznC mutants did not colonize the stomach in a Mongolian gerbil
      based animal model. This demonstrates that the metal export functions of H.
      pylori cznABC are essential for gastric colonization and underlines the
      extraordinary importance of metal ion homeostasis for the survival of H. pylori
      in the gastric environment.

PMID- 16790757
TI  - Protein expression profiles of Chlamydia pneumoniae in models of persistence
      versus those of heat shock stress response.
AB  - Chlamydia pneumoniae is an obligate intracellular pathogen that causes both acute
      and chronic human disease. Several in vitro models of chlamydial persistence have
      been established to mimic chlamydial persistence in vivo. We determined the
      expression patterns of 52 C. pneumoniae proteins, representing nine functional
      subgroups, from the gamma interferon (IFN-gamma) treatment (primarily tryptophan
      limitation) and iron limitation (IL) models of persistence compared to those
      following heat shock (HS) at 42 degrees C. Protein expression patterns of C.
      pneumoniae persistence indicates a strong stress component, as evidenced by the
      upregulation of proteins involved in protein folding, assembly, and modification.
      However, it is clearly more than just a stress response. In IFN persistence, but
      not IL or HS, amino acid and/or nucleotide biosynthesis proteins were found to be
      significantly upregulated. In contrast, proteins involved in the biosynthesis of
      cofactors, cellular processes, energy metabolism, transcription, and translation
      showed an increased in expression in only the IL model of persistence. These data
      represent the most extensive protein expression study of C. pneumoniae comparing
      the chlamydial heat shock stress response to two models of persistence and
      identifying the common and unique protein level responses during persistence.

PMID- 16790758
TI  - Serologic proteome analysis of Borrelia burgdorferi membrane-associated proteins.
AB  - Lyme disease, a global health concern, is caused by infection with Borrelia
      burgdorferi, B. afzelii, or B. garinii. The spirochete responsible for the
      disease in the United States is B. burgdorferi and is spread by the bite of an
      infected Ixodes tick. We utilized multiple two-dimensional gel techniques
      combined with proteomics to reveal the full humoral immune response of mice and
      Lyme patients to membrane-associated proteins isolated from Borrelia burgdorferi.
      Our studies indicated that a subset of immunogenic membrane-associated proteins
      (some new and some previously identified) was recognized by mice experimentally
      infected with Borrelia burgdorferi either by low-dose needle inoculation or by
      tick infestation. Moreover, the majority of these immunogenic membrane-associated
      proteins were recognized by sera from patients diagnosed with early-disseminated
      Lyme disease. These included RevA, ErpA, ErpP, DbpA, BmpA, FtsZ, ErpB, LA7, OppA
      I, OppA II, OppA IV, FlhF, BBA64, BBA66, and BB0323. Some immunogens (i.e.,
      BBI36/38) were more reactive with sera from mice than Lyme patients, while
      additional membrane proteins (i.e., FlaB, P66, LA7, and Hsp90) were recognized
      more strongly with sera from patients diagnosed with early-localized, early
      disseminated, or late (chronic)-stage Lyme disease. We were able to examine the
      humoral response in Lyme patients in a temporal fashion and to identify the
      majority of immunoreactive proteins as the disease progresses from early to late
      stages. This serologic proteome analysis enabled the identification of novel
      membrane-associated proteins that may serve as new diagnostic markers and, more
      importantly, as second-generation vaccine candidates for protection against Lyme
      disease.

PMID- 16790759
TI  - Deletion of znuA virulence factor attenuates Brucella abortus and confers
      protection against wild-type challenge.
AB  - znuA is known to be an important factor for survival and normal growth under low
      Zn(2+) concentrations for Escherichia coli, Haemophilus spp., Neisseria
      gonorrhoeae, and Pasteurella multocida. We hypothesized that the znuA gene
      present in Brucella melitensis 16 M would be similar to znuA in B. abortus and
      questioned whether it may also be an important factor for growth and virulence of
      Brucella abortus. Using the B. melitensis 16 M genome sequence, primers were
      designed to construct a B. abortus deletion mutant. A znuA knockout mutation in
      B. abortus 2308 (DeltaznuA) was constructed and found to be lethal in low-Zn(2+)
      medium. When used to infect macrophages, DeltaznuA B. abortus showed minimal
      growth. Further study with DeltaznuA B. abortus showed that its virulence in
      BALB/c mice was attenuated, and most of the bacteria were cleared from the spleen
      within 8 weeks. Protection studies confirmed the DeltaznuA mutant as a potential
      live vaccine, since protection against wild-type B. abortus 2308 challenge was as
      effective as that obtained with the RB51 or S19 vaccine strain.

PMID- 16790761
TI  - Doxycycline reduces mortality and injury to the brain and cochlea in experimental
      pneumococcal meningitis.
AB  - Bacterial meningitis is characterized by an inflammatory reaction to the invading
      pathogens that can ultimately lead to sensorineural hearing loss, permanent brain
      injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor
      alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood
      brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline
      is a clinically used antibiotic with anti-inflammatory effects that lead to
      reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited
      TACE with a 50% inhibitory dose of 74 microM in vitro and reduced the amount of
      tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo.
      In an infant rat model of pneumococcal meningitis, a single dose of doxycycline
      (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after
      infection significantly reduced the mortality, the blood-brain barrier
      disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30
      mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss,
      as assessed by auditory brainstem response audiometry, and neuronal death in the
      cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably
      as a result of its anti-inflammatory properties, had broad beneficial effects in
      the brain and the cochlea and improved survival in this model of pneumococcal
      meningitis in infant rats.

PMID- 16790760
TI  - Type III secretion-dependent modulation of innate immunity as one of multiple
      factors regulated by Pseudomonas aeruginosa RetS.
AB  - Mutation of retS (rtsM) of Pseudomonas aeruginosa strain PA103 reduces its
      virulence in both ocular and respiratory murine models of infection. In vitro,
      retS mutants exhibit loss of the ExsA-regulated type III secretion system (TTSS),
      reduced twitching motility, and a decrease in association with, invasion of, and
      survival within corneal epithelial cells. In addition, transcription of multiple
      other virulence genes is positively and negatively affected by retS mutation.
      Since our published data show that ExoU and ExoT, the two TTSS effectors encoded
      by strain PA103, each confer virulence in this corneal model, we hypothesized
      that loss of virulence of retS mutants follows loss of type III secretion.
      Corneal pathology, bacterial colonization, and phagocyte infiltration were
      compared for wild-type PA103, retS mutants, and various TTSS mutants after
      infection with approximately 10(6) CFU bacteria. Results showed that either a
      retS or an exsA (TTSS) mutation delayed disease progression, as illustrated by
      reduced severity scores and colonization levels during the first 48 h
      postinfection. Surprisingly, retS mutant infections then became more severe than
      those involving exsA mutants. By day 7, colonization levels of retS mutants even
      surpassed those of wild-type bacteria (more than twofold, P = 0.028). Although
      retS mutants caused more severe opacification of central corneas than both the
      wild type and the exsA mutants, neither mutant caused the peripheral ring opacity
      commonly associated with wild-type infection, suggesting that the TTSS was
      involved. Histological experiments with retS and various TTSS mutants showed that
      ring opacification required ExoU but not ExoT and that it consisted of dense
      polymorphonuclear phagocyte infiltration at the corneal periphery and the absence
      of any cell type in the central cornea. These data suggest that these P.
      aeruginosa TTSS effectors have different effects on innate immunity and that RetS
      influences virulence beyond its effects on the TTSS.

PMID- 16790762
TI  - Mucosal immunity to asymptomatic Entamoeba histolytica and Entamoeba dispar
      infection is associated with a peak intestinal anti-lectin immunoglobulin A
      antibody response.
AB  - We monitored 93 subjects cured of amebic liver abscess (ALA) and 963 close
      associate controls in Durban, South Africa, and determined by enzyme-linked
      immunosorbent assay that the intestinal immunoglobulin A (IgA) antibody response
      to the Entamoeba histolytica galactose-inhibitable adherence lectin is most
      accurately represented by a complex pattern of transitory peaks. One or more
      intestinal anti-lectin IgA antibody peaks occurred in 85.9% of ALA subjects over
      36 months compared to 41.6% of controls (P < 0.0001). ALA subjects exhibited a
      greater number of anti-lectin IgA antibody peaks (P < 0.0001) than controls. In
      addition, their peak optical density values were higher (peak numbers 1 to 3, P <
      0.003), peaks were of longer duration (for peaks 1 and 2, P </= 0.0054), and
      there was a shorter time interval between peaks (between 1 and 2 or 2 and 3, P
      </= 0.0106) than observed for control subjects. A prior E. histolytica infection
      was associated with the occurrence of an anti-lectin IgA antibody peak (79.1%, P
      < 0.0001) more so than for Entamoeba dispar infection (57.2%, P < 0.001). The
      annual number of anti-lectin IgA antibody peaks in ALA subjects was 0.71 per
      year, compared to just 0.22 in controls (P<0.0001), indicating a higher rate of
      exposure to the parasite than previously appreciated. Anti-lectin IgA antibody
      peaks were of higher amplitude following a E. histolytica infection compared to
      E. dispar (P = 0.01) and, for either, were of greater height in ALA subjects than
      controls (P < 0.01). ALA subjects demonstrated greater clearance of amebic
      infection after an anti-lectin IgA antibody peak compared to controls, and only
      14.3% remained with a positive culture after the peak, compared to 38.9% in
      controls (P = 0.035). In summary, this prospective controlled longitudinal study
      elucidated the dynamic nature of the human intestinal IgA antibody response to E.
      histolytica and E. dispar infection and revealed that ALA subjects exhibit
      heightened intestinal anti-lectin IgA antibody peaks that are associated with
      clearance of E. histolytica and E. dispar infection.

PMID- 16790763
TI  - Differential expression of var gene groups is associated with morbidity caused by
      Plasmodium falciparum infection in Tanzanian children.
AB  - The var gene family of Plasmodium falciparum encodes the variant surface antigen
      Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is
      considered an important pathogenicity factor in P. falciparum infection because
      it mediates cytoadherence to host cell endothelial receptors. var genes can be
      grouped into three major groups, A, B, and C, and the conserved var genes, var1
      4, according to sequence similarities in coding and noncoding upstream regions.
      Using real-time quantitative PCR in a study conducted in Tanzania, the var
      transcript abundances of the different var gene groups were compared among
      patients with severe, uncomplicated, and asymptomatic malaria. Transcripts of var
      group A and B genes were more abundant in patients with severe malaria than in
      patients with uncomplicated malaria. In general, the transcript abundances of var
      group A and B genes were higher for children with clinical malaria than for
      children with asymptomatic infections. The var group C and var1-like transcript
      abundances were similar between the three sample groups. A transcript abundance
      pattern similar to that for var group A was observed for var2csa and var3-like
      genes. These results suggest that substantial and systematic differences in var
      gene expression exist between different clinical presentations.

PMID- 16790764
TI  - Leishmania infection impairs beta 1-integrin function and chemokine receptor
      expression in mononuclear phagocytes.
AB  - Leishmania spp. are intracellular parasites that cause lesions in the skin,
      mucosa, and viscera. We have previously shown that Leishmania infection reduces
      mononuclear phagocyte adhesion to inflamed connective tissue. In this study, we
      examined the role of adhesion molecules and chemokines in this process. Infection
      rate (r = -0.826, P = 0.003) and parasite burden (r = -0.917, P = 0.028)
      negatively correlated to mouse phagocyte adhesion. The decrease (58.7 to 75.0%
      inhibition, P = 0.005) in phagocyte adhesion to connective tissue, induced by
      Leishmania, occurred as early as 2 h after infection and was maintained for at
      least 24 h. Interestingly, impairment of cell adhesion was sustained by phagocyte
      infection, since it was not observed following phagocytosis of killed parasites
      (cell adhesion varied from 15.2% below to 24.0% above control levels, P > 0.05).
      In addition, Leishmania infection diminished cell adhesion to fibronectin (54.1
      to 96.2%, P < 0.01), collagen (15.7 to 83.7%, P < 0.05), and laminin (59.1 to
      82.2%, P < 0.05). The CD11b(hi) subpopulation was highly infected (49.6 to
      97.3%). Calcium and Mg(2+) replacement by Mn(2+), a treatment that is known to
      induce integrins to a high state of affinity for their receptors, reverted the
      inhibition in adhesion caused by Leishmania. This reversion was completely
      blocked by anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two
      chemokine receptors implicated in cell adhesion, was found to be downregulated 16
      h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively).
      Together, these results suggest that mechanisms regulating integrin function are
      implicated in the change of macrophage adhesion in leishmaniasis.

PMID- 16790766
TI  - CPS1, a homolog of the Streptococcus pneumoniae type 3 polysaccharide synthase
      gene, is important for the pathobiology of Cryptococcus neoformans.
AB  - The polysaccharide capsule is known to be the major factor required for the
      virulence of Cryptococcus neoformans. We have cloned and characterized a gene,
      designated CPS1, that encodes a protein containing a glycosyltransferase moiety
      and shares similarity with the type 3 polysaccharide synthase encoded by the
      cap3B gene of Streptococcus pneumoniae. Cps1p also shares similarity with
      hyaluronan synthase of higher eukaryotes. Deletion of the CPS1 gene from a
      serotype D strain of C. neoformans resulted in a slight reduction of the capsule
      size as observed by using an India ink preparation. The growth at 37 degrees C
      was impaired, and the ability to associate with human brain endothelial cells in
      vitro was also significantly reduced by the deletion of CPS1. Using site-specific
      mutagenesis, we showed that the conserved glycosyltransferase domains are
      critical for the ability of the strain to grow at elevated temperatures. A
      hyaluronan enzyme-linked immunosorbent assay method demonstrated that CPS1 is
      important for the synthesis of hyaluronan or its related polysaccharides in C.
      neoformans. Comparisons between the wild-type and the cps1Delta strains, using
      three different transmission electron microscopic methods, indicated that the
      CPS1 gene product is involved in the composition or maintenance of an electron
      dense layer between the outer cell wall and the capsule. These and the virulence
      studies in a mouse model suggested that the CPS1 gene is important in the
      pathobiology of C. neoformans.

PMID- 16790765
TI  - Molecular cloning of a Trypanosoma cruzi cell surface casein kinase II substrate,
      Tc-1, involved in cellular infection.
AB  - In this work, we report the cloning and characterization of the first cell
      surface casein kinase II (CKII) substrate (Tc-1) of Trypanosoma cruzi, the
      causative agent of Chagas' disease. Analysis of the gene sequence revealed a
      1,653-bp open reading frame coding for 550 amino acid residues. Northern blot
      analysis showed a 4.5-kb transcript that is expressed in invasive trypomastigotes
      but not in noninvasive epimastigote forms of T. cruzi. Southern blot analysis
      indicates that Tc-1 is a single-copy gene. At the amino acid level, Tc-1
      displayed 95% and 99% identity to two hypothetical proteins recently reported by
      the T. cruzi genome project. Analysis of the translated amino acid sequence
      indicates that the Tc-1 gene has a putative transmembrane domain with multiple
      cytoplasmic and extracellular CKII phosphosites. Exogenous human CKII was able to
      phosphorylate serine residues on both recombinant Tc-1 and Tc-1 of intact
      trypomastigotes. This phosphorylation was inhibited by the CKII inhibitors
      heparin and 4,5,6,7,-tetrabromo-2-azabenzimidazole. Immunoblots of solubilized
      trypomastigotes, epimastigotes, and amastigotes probed with anti-recombinant Tc-1
      immunoglobulin G revealed a 62-kDa protein that is expressed only in infective
      trypomastigotes. Immunoprecipitation of labeled surface proteins of
      trypomastigotes indicated that the 62-kDa protein is a surface protein, and we
      found that the protein is uniformly distributed on the surface of trypomastigotes
      by direct immunofluorescence. Antibodies to Tc-1 effectively blocked
      trypomastigote invasion of host cells and consequently reduced parasite load.
      Preincubation of either trypomastigotes or myoblasts with CKII inhibitors blocked
      T. cruzi infection. Thus, for the first time, we describe a cell surface CKII
      substrate of a protozoan parasite that is phosphorylated by human CKII and that
      is involved in cellular infection.

PMID- 16790767
TI  - Cloning, characterization, and serodiagnostic evaluation of Leishmania infantum
      tandem repeat proteins.
AB  - Visceral leishmaniasis (VL) is a form of leishmaniasis, which is caused by
      infection with the protozoan parasite Leishmania, and is often fatal unless it is
      treated. Rapid and accurate diagnosis of VL is important for effective treatment.
      Here we report the cloning of previously undescribed tandem repeat (TR) proteins
      of Leishmania infantum and an evaluation of VL patient antibody responses to the
      corresponding proteins. By screening an L. infantum expression library with sera
      from human VL patients or infected hamsters, we identified 43 genes encoding B
      cell antigens. Surprisingly, 19 of the 43 genes (44%) were TR proteins, and that
      percentage was significantly higher than that for genes picked randomly from the
      database. We then expressed the TR regions of LinJ16.1750, LinJ22.1590, and
      LinJ33.2870 and the entire LinJ28.2310 protein. These recombinant proteins were
      all recognized by Sudanese VL patient sera in an enzyme-linked immunosorbent
      assay. Recombinant LinJ16.1750 (rLinJ16.1750) showed the best performance among
      these antigens in terms of both sensitivity and specificity. Serological
      evaluation revealed that 97% (34 of 35) of Sudanese VL patients had significantly
      elevated antibody levels to rLinJ16.1750. Furthermore, when eight of the patient
      sera which had low reactivities to rK39 were tested with the novel recombinant
      antigens, some of the sera showed stronger antibody responses to these antigens
      than to rK39. Our results suggest that TR regions from the novel L. infantum
      proteins identified in this study are immunodominant B-cell epitopes and may
      represent good candidates for serodiagnosis of VL.

PMID- 16790768
TI  - Comparison of different live vaccine strategies in vivo for delivery of protein
      antigen or antigen-encoding DNA and mRNA by virulence-attenuated Listeria
      monocytogenes.
AB  - Listeria monocytogenes can be used to deliver protein antigens or DNA and mRNA
      encoding such antigens directly into the cytosol of host cells because of its
      intracellular lifestyle. In this study, we compare the in vivo efficiencies of
      activation of antigen-specific CD8 and CD4 T cells when the antigen is secreted
      by L. monocytogenes or when antigen-encoding plasmid DNA or mRNA is released by
      self-destructing strains of L. monocytogenes. Infection of mice with self
      destructing L. monocytogenes carriers delivering mRNA that encodes a nonsecreted
      form of ovalbumin (OVA) resulted in a significant OVA-specific CD8 T-cell
      response. In contrast, infection with L. monocytogenes delivering OVA-encoding
      DNA failed to generate specific T cells. Secretion of OVA by the carrier bacteria
      yielded the strongest immune response involving OVA-specific CD8 and CD4 T cells.
      In addition, we investigated the antigen delivery capacity of a self-destructing,
      virulence-attenuated L. monocytogenes aroA/B mutant. In contrast to the wild-type
      strain, this mutant exhibited only marginal liver toxicity when high doses (5 x
      10(7) CFU per animal administered intravenously) were used, and it was also able
      to deliver sufficient amounts of secreted OVA into mice. Therefore, the results
      presented here could lay the groundwork for a rational combination of L.
      monocytogenes as an attenuated carrier for the delivery of protein and nucleic
      acid vaccines in novel vaccination strategies.

PMID- 16790769
TI  - T-cell expression cloning of Porphyromonas gingivalis genes coding for T helper
      biased immune responses during infection.
AB  - Exposure of the mouse oral cavity to Porphyromonas gingivalis results in the
      development of gingivitis and periapical bone loss, which apparently are
      associated with a Th1 response to bacterial antigens. We have used this infection
      model in conjunction with direct T-cell expression cloning to identify bacterial
      antigens that induce a preferential or biased T helper response during the
      infectious process. A P. gingivalis-specific CD4 T-cell line derived from mice at
      3 weeks postchallenge was used to directly screen a P. gingivalis genomic
      expression library. This screen resulted in the identification of five genes
      coding for previously identified proteins and three other putative protein
      antigens. One of the identified proteins, P. gingivalis thiol peroxidase, was
      studied in detail because this molecule belongs to a protein family that is
      apparently involved in microbial pathogenesis. Infection of mice with P.
      gingivalis, either via the subcutaneous route or after exposure of the animal's
      oral cavity to viable bacteria, resulted in the induction of a strong thiol
      peroxidase-specific immune response characterized by the production of high
      titers of specific serum immunoglobulin G2a antibody and the production of gamma
      interferon by antigen-stimulated lymphoid cells, a typical Th1-biased response.
      Thus, the use of a proven T-cell expression cloning approach and a mouse model of
      periodontal disease resulted in the identification and characterization of P.
      gingivalis proteins that might be involved in pathogenesis.

PMID- 16790770
TI  - Circulating gamma delta T cells in response to Salmonella enterica serovar
      enteritidis exposure in chickens.
AB  - gammadelta T cells are considered crucial to the outcome of various infectious
      diseases. The present study was undertaken to characterize gammadelta (T-cell
      receptor 1(+) [TCR1(+)]) T cells phenotypically and functionally in avian immune
      response. Day-old chicks were orally immunized with Salmonella enterica serovar
      Enteritidis live vaccine or S. enterica serovar Enteritidis wild-type strain and
      infected using the S. enterica serovar Enteritidis wild-type strain on day 44 of
      life. Between days 3 and 71, peripheral blood was examined flow cytometrically
      for the occurrence of gammadelta T-cell subpopulations differentiated by the
      expression of T-cell antigens. Three different TCR1(+) cell populations were
      found to display considerable variation regarding CD8alpha antigen expression:
      (i) CD8alpha(+high) TCR1(+) cells, (ii) CD8alpha(+dim) TCR1(+) cells, and (iii)
      CD8alpha(-) TCR1(+) cells. While most of the CD8alpha(+high) TCR1(+) cells
      expressed the CD8alphabeta heterodimeric antigen, the majority of the
      CD8alpha(+dim) TCR1(+) cells were found to express the CD8alphaalpha homodimeric
      form. After immunization, a significant increase of CD8alphaalpha(+high)
      gammadelta T cells was observed within the CD8alpha(+high) TCR1(+) cell
      population. Quantitative reverse transcription-PCR revealed reduced interleukin-7
      receptor alpha (IL-7Ralpha) and Bcl-x expression and elevated IL-2Ralpha mRNA
      expression of the CD8alphaalpha(+high) gammadelta T cells. Immunohistochemical
      analysis demonstrated a significant increase of CD8alpha(+) and TCR1(+) cells in
      the cecum and spleen and a decreased percentage of CD8beta(+) T cells in the
      spleen after Salmonella immunization. After infection of immunized animals,
      immune reactions were restricted to intestinal tissue. The study showed that
      Salmonella immunization of very young chicks is accompanied by an increase of
      CD8alphaalpha(+high) gammadelta T cells in peripheral blood, which are probably
      activated, and thus represent an important factor for the development of a
      protective immune response to Salmonella organisms in chickens.

PMID- 16790771
TI  - Previous or ongoing schistosome infections do not compromise the efficacy of the
      attenuated cercaria vaccine.
AB  - A current or previous schistosome infection might compromise the efficacy of a
      schistosome vaccine administered to humans. We have therefore investigated the
      influence of infection on vaccination, using the baboon as the model host and
      irradiated Schistosoma mansoni cercariae as the vaccine. Protection, determined
      from worm burdens in test and controls, was not diminished when vaccination was
      superimposed on a chronic infection, nor was it diminished when it followed a
      primary infection terminated by chemotherapy. Protection was also assessed
      indirectly based on fecal egg output and circulating antigen levels, as would be
      the case in human vaccine trials. In almost all instances, these methods
      overestimated protection, sometimes with discrepancies of >20%. The overwhelming
      immune response to egg deposition in infected animals made it difficult to
      discern a contribution from vaccination. Nevertheless, the well-documented
      immunomodulation of immune responses that follows egg deposition did not appear
      to impede the protective mechanisms elicited by vaccination with attenuated
      cercariae.

PMID- 16790773
TI  - Identification, recombinant expression, immunolocalization in macrophages, and T
      cell responsiveness of the major extracellular proteins of Francisella
      tularensis.
AB  - A safer and more effective vaccine than the previously developed live attenuated
      vaccine is needed for combating Francisella tularensis, a highly infectious
      bacterial pathogen. To search for potential candidates for inclusion in a new
      vaccine, we characterized the proteins present in the culture filtrates of a
      virulent recent clinical isolate and the attenuated live vaccine strain of F.
      tularensis using a proteomic approach. We identified a total of 12 proteins;
      among these, catalase-peroxidase was much more abundant in the culture filtrate
      of the virulent clinical isolate, whereas bacterioferritin was more abundant in
      the culture filtrate of the live vaccine strain. Streptolysin O treatment of
      infected human macrophages indicated that catalase-peroxidase and the heat shock
      protein GroEL are released intracellularly by actively growing F. tularensis.
      Mice immunized with F. tularensis developed significant cell-mediated immune
      responses to catalase-peroxidase, the heat shock protein GroEL, and
      bacterioferritin as measured by splenic lymphocyte proliferation and gamma
      interferon production. Finally, we expressed the major culture filtrate proteins
      that are promising vaccine candidates in Escherichia coli at high levels in
      soluble form to facilitate study of their immunobiology and potential role in
      vaccines.

PMID- 16790772
TI  - Search for Bacillus anthracis potential vaccine candidates by a functional
      genomic-serologic screen.
AB  - Bacillus anthracis proteins that possess antigenic properties and are able to
      evoke an immune response were identified by a reductive genomic-serologic screen
      of a set of in silico-preselected open reading frames (ORFs). The screen included
      in vitro expression of the selected ORFs by coupled transcription and translation
      of linear PCR-generated DNA fragments, followed by immunoprecipitation with
      antisera from B. anthracis-infected animals. Of the 197 selected ORFs, 161 were
      chromosomal and 36 were on plasmids pXO1 and pXO2, and 138 of the 197 ORFs had
      putative functional annotations (known ORFs) and 59 had no assigned functions
      (unknown ORFs). A total of 129 of the known ORFs (93%) could be expressed,
      whereas only 38 (64%) of the unknown ORFs were successfully expressed. All 167
      expressed polypeptides were subjected to immunoprecipitation with the anti-B.
      anthracis antisera, which revealed 52 seroreactive immunogens, only 1 of which
      was encoded by an unknown ORF. The high percentage of seroreactive ORFs among the
      functionally annotated ORFs (37%; 51/129) attests to the predictive value of the
      bioinformatic strategy used for vaccine candidate selection. Furthermore, the
      experimental findings suggest that surface-anchored proteins and adhesins or
      transporters, such as cell wall hydrolases, proteins involved in iron
      acquisition, and amino acid and oligopeptide transporters, have great potential
      to be immunogenic. Most of the seroreactive ORFs that were tested as DNA vaccines
      indeed appeared to induce a humoral response in mice. We list more than 30 novel
      B. anthracis immunoreactive virulence-related proteins which could be useful in
      diagnosis, pathogenesis studies, and future anthrax vaccine development.

PMID- 16790774
TI  - Pneumococcal neuraminidases A and B both have essential roles during infection of
      the respiratory tract and sepsis.
AB  - We examined the role of the neuraminidases NanA and NanB in colonization and
      infection in the upper and lower respiratory tract by Streptococcus pneumoniae,
      as well as the role of these neuraminidases in the onset and development of
      septicemia following both intranasal and intravenous infection. We demonstrated
      for the first time using outbred MF1 mouse models of infection that both NanA and
      NanB were essential for the successful colonization and infection of the upper
      and lower respiratory tract, respectively, as well as pneumococcal survival in
      nonmucosal sites, such as the blood. Our studies have shown that in vivo a
      neuraminidase A mutant is cleared from the nasopharynx, trachea, and lungs within
      12 h postinfection, while a neuraminidase B mutant persists but does not increase
      in either the nasopharynx, trachea, or lungs. We also demonstrated both
      neuraminidase mutants were unable to cause sepsis following intranasal
      infections. When administered intravenously, however, both mutants survived
      initially but were unable to persist in the blood beyond 48 h postinfection and
      were progressively cleared. The work presented here demonstrates the importance
      of pneumococcal neuraminidase A and for the first time neuraminidase B in the
      development of upper and lower respiratory tract infection and sepsis.

PMID- 16790775
TI  - The Actinobacillus actinomycetemcomitans ribose binding protein RbsB interacts
      with cognate and heterologous autoinducer 2 signals.
AB  - Autoinducer 2 (AI-2) produced by the oral pathogen Actinobacillus
      actinomycetemcomitans influences growth of the organism under iron limitation and
      regulates the expression of iron uptake genes. However, the cellular components
      that mediate the response of A. actinomycetemcomitans to AI-2 have not been fully
      characterized. Analysis of the complete genome sequence of A.
      actinomycetemcomitans (www.oralgen.lanl.gov) indicated that the RbsB protein was
      related to LuxP, the AI-2 receptor of Vibrio harveyi. To determine if RbsB
      interacts with AI-2, the bioluminescence of the reporter strain V. harveyi BB170
      (sensor 1-, sensor 2+) was determined after stimulation with partially purified
      AI-2 from A. actinomycetemcomitans or conditioned medium from V. harveyi cultures
      in the presence and absence of purified six-His-tagged RbsB. RbsB efficiently
      inhibited V. harveyi bioluminescence induced by both A. actinomycetemcomitans AI
      2 and V. harveyi AI-2 in a dose-dependent manner, suggesting that RbsB competes
      with LuxP for AI-2. Fifty percent inhibition occurred with approximately 0.3 nM
      RbsB for A. actinomycetemcomitans AI-2 and 15 nM RbsB for V. harveyi AI-2. RbsB
      mediated inhibition of V. harveyi bioluminescence was reversed by the addition of
      50 mM ribose, suggesting that A. actinomycetemcomitans AI-2 and ribose bind at
      the same site of RbsB. The RbsB/AI-2 complex was thermostable since A.
      actinomycetemcomitans AI-2 could not be recovered by heating. This was not due to
      heat inactivation of A. actinomycetemcomitans AI-2 since signal activity was
      unaffected by heating in the absence of RbsB. Furthermore, an isogenic A.
      actinomycetemcomitans mutant that was unable to express rbsB was deficient in
      depleting A. actinomycetemcomitans AI-2 from solution relative to the wild-type
      organism. Inactivation of rbsB also influenced the ability of the organism to
      grow under iron-limiting conditions. The mutant strain attained a cell density of
      approximately 30% that of the wild-type organism under iron limitation. In
      addition, real-time PCR showed that the expression of afuABC, encoding a major
      ferric ion transporter, was reduced by approximately eightfold in the rbsB
      mutant. This phenotype was similar to that of a LuxS-deficient mutant of A.
      actinomycetemcomitans that is unable to produce AI-2. Together, our results
      suggest that RbsB may play a role in the response of A. actinomycetemcomitans to
      AI-2.

PMID- 16790776
TI  - Role of sigma E-regulated genes in Escherichia coli uropathogenesis.
AB  - The sigma E regulon encodes proteins for maintenance and repair of the
      Escherichia coli cell envelope. Previously, we observed that an antirepressor of
      sigma E, DegS, is essential for uropathogenic E. coli virulence. Here we use a
      mouse urinary tract infection model to assay the virulence of mutants of E. coli
      genes described as sigma E dependent. Deletion mutants of candidate genes were
      made in the uropathogenic E. coli strain CFT073. Swiss Webster female mice were
      inoculated with a mixture of mutant and wild-type strains. Bladder and kidney
      homogenates were cultured 2 days after infection, and CFU of the wild type and
      mutant were compared. Eleven mutants were assayed, and two, CFT073 degP and
      CFT073 skp, showed significantly diminished survival compared to wild type. DegP
      is a chaperone and degradase active in the periplasm. Skp is also a periplasmic
      chaperone. The virulence of the skp deletion mutant could not be restored by
      complementation with skp. The virulence of the degP deletion mutant, in contrast,
      could be restored. However, complementation with a degP allele encoding a serine
      to-alanine (S210A) mutation at the protease active site fails to restore
      virulence. Unlike degP mutants in other bacteria, the E. coli degP mutant is
      tolerant of oxidative stress. It disappears abruptly from bladder and kidney
      cultures between 6 and 12 hours after inoculation. A mutant of degQ, a close
      homolog of degP, was not attenuated in mice. This is the first report that the
      DegP degradase is an E. coli virulence factor in an animal infection model.

PMID- 16790777
TI  - HbiF regulates type 1 fimbriation independently of FimB and FimE.
AB  - Type 1 fimbriae have been suggested to play a role in the pathogenesis of
      extraintestinal Escherichia coli infection. Type 1 fimbriation in E. coli is
      phase variable and known to be dependent upon FimB and FimE, the two recombinases
      that invert the molecular switch fimS and control the expression of the
      downstream fim operon. Here we showed that HbiF, a novel site-specific
      recombinase, inverted fimS independently of FimB and FimE. HbiF-mediated fimS
      inversion appeared to be predominantly switching from "off" (termed OFF) to "on"
      (termed ON) orientation. This is different from the fimS inversion mediated by
      either FimB (bidirectional ON to OFF and OFF to ON) or FimE (unidirectional ON to
      OFF). Constitutive expression of the hbiF gene in E. coli resulted in a fimS
      locked-ON phenotype, which resulted in the pathogenic E. coli K1 strain being
      incapable of inducing a high degree of bacteremia in neonatal rats. Discovery of
      HbiF-mediated OFF-to-ON fimS switching provides a new opportunity to develop a
      strategy for the prevention and therapy of extraintestinal E. coli infection
      including bacteremia and meningitis.

PMID- 16790778
TI  - Evaluation of protection afforded by Brucella abortus and Brucella melitensis
      unmarked deletion mutants exhibiting different rates of clearance in BALB/c mice.
AB  - Research for novel Brucella vaccines has focused upon the development of live
      vaccine strains, which have proven more efficacious than killed or subunit
      vaccines. In an effort to develop improved vaccines, signature-tagged mutant
      banks were screened to identify mutants attenuated for survival. Mutants selected
      from these screens exhibited various degrees of attenuation characterized by the
      rate of clearance, ranging from a failure to grow in macrophages after 24 h of
      infection to a failure to persist in the mouse model beyond 8 weeks. Ideal
      vaccine candidates should be safe to the host, while evoking protective immunity.
      In the present work, we constructed unmarked deletion mutants of three gene
      candidates, manBA, virB2, and asp24, in both Brucella abortus and Brucella
      melitensis. The Deltaasp24 mutants, which persist for extended periods in vivo,
      are superior to current vaccine strains and to other deletion strains tested in
      the mouse model against homologous challenge infection after 12, 16, and 20 weeks
      postvaccination. The Deltaasp24 mutants also display superior protection compared
      to DeltamanBA and DeltavirB2 mutants against heterologous challenge in mice. From
      this study, a direct association between protection against infection and
      cytokine response was not apparent between all vaccine groups and, therefore,
      correlates of protective immunity will need to be considered further. A distinct
      correlation between persistence of the vaccine strain and protection against
      infection was corroborated.

PMID- 16790779
TI  - Glycoprotein 340 in normal human ocular surface tissues and tear film.
AB  - The tear film is a complex mixture of secreted fluid, ions, proteins,
      glycoproteins, and lipids that lubricates and protects the ocular surface.
      Recently, several antimicrobial peptides have been described in the tear fluid.
      In this study, we describe the presence of the large secreted glycoprotein gp340
      in the tear film. Western blot analysis showed that gp340 is abundant in secreted
      tears and in the lacrimal glands. Lesser amounts of gp340 were detected in the
      cornea and conjunctiva. Consistent with Western blot data, reverse transcription
      PCR and real-time quantitative PCR showed that gp340 transcripts were abundant in
      lacrimal gland tissue and were also present in the cornea and conjunctiva.
      Immunohistochemistry localized gp340 to the acinar cells of the lacrimal gland
      and the deeper layers of the conjunctival epithelium. gp340 was not detected in
      conjunctival goblet cells. In the cornea, gp340 was present only in a peripheral
      band of basal epithelial cells, suggesting that gp340 may play a role in the
      cycle of corneal epithelial renewal. To determine if tear film gp340 may function
      as a bacterial agglutinin as it does in saliva, tears were incubated with
      streptococcal cells and the formation of bacterial aggregates was monitored.
      Addition of tears to late-exponential-phase Streptococcus mutans cells resulted
      in time- and dose-dependent aggregation of the bacteria. Furthermore, Western
      blot analysis confirmed the presence of cell-associated gp340 in isolated
      bacterial aggregates. The ocular pathogen Staphylococcus aureus, but not
      Pseudomonas aeruginosa, also aggregated when incubated with tears. These results
      suggest that gp340 is a normal component of the tear film and that the
      glycoprotein may function as a bacterial agglutinin.

PMID- 16790780
TI  - Identification of markers for Helicobacter pylori strains isolated from children
      with peptic ulcer disease by suppressive subtractive hybridization.
AB  - Peptic ulcer disease (PUD) occurs after a long-term Helicobacter pylori
      infection. However, the disease can develop earlier, and rare cases have been
      observed in children, suggesting that these H. pylori strains may be more
      virulent. We used suppressive subtractive hybridization for comparative genomics
      between H. pylori strains isolated from a 5-year-old child with duodenal ulcer
      and from a sex- and age-matched child with gastritis only. The prevalence of the
      30 tester-specific subtracted sequences was determined on a collection of H.
      pylori strains from children (15 ulcers and 30 gastritis) and from adults (46
      ulcers and 44 gastritis). Two of these sequences, jhp0562 (80.0% versus 33.3%, P
      = 0.008) and jhp0870 (80.0% versus 36.7%, P = 0.015), were highly associated with
      PUD in children and a third sequence, jhp0828, was less associated (40.0% versus
      10.0%, P = 0.048). Among adult strains, none of the 30 sequences was associated
      with PUD. However, both jhp0562 and jhp0870 were less prevalent in adenocarcinoma
      strains than in PUD strains from children and adults, the difference being
      statistically significant for jhp0870. In conclusion, two H. pylori genes were
      identified as being strongly associated with PUD in children, and their putative
      roles as an outer membrane protein for jhp0870 and in lipopolysaccharide
      biosynthesis for jhp0562, suggest that they may be novel virulence factors of H.
      pylori.

PMID- 16790781
TI  - Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll
      like receptor 2- and toll-like receptor 4-dependent pathways.
AB  - Toll-like receptors (TLRs) are key components of the innate immune system that
      trigger antimicrobial host defense responses. The aim of the present study was to
      analyze the effects of probiotic Escherichia coli Nissle strain 1917 in
      experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was
      induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via
      administration of 5% dextran sodium sulfate (DSS). Mice were treated with either
      0.9% NaCl or 10(7) E. coli Nissle 1917 twice daily, followed by the determination
      of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2
      knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice
      developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4
      knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased
      proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction
      of gamma interferon secretion was observed after E. coli Nissle 1917 treatment.
      In TLR-4 knockout mice, cytokine secretion was almost undetectable and not
      modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not
      develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and
      human T cells increased TLR-2 and TLR-4 protein expression in T cells and
      increased NF-kappaB activity via TLR-2 and TLR-4. In conclusion, our data provide
      evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in
      mice via TLR-2- and TLR-4-dependent pathways.

PMID- 16790782
TI  - Burkholderia cenocepacia ZmpB is a broad-specificity zinc metalloprotease
      involved in virulence.
AB  - In previous studies we characterized the Burkholderia cenocepacia ZmpA zinc
      metalloprotease. In this study, we determined that B. cenocepacia has an
      additional metalloprotease, which we designated ZmpB. The zmpB gene is present in
      the same species as zmpA and was detected in B. cepacia, B. cenocepacia, B.
      stabilis, B. ambifaria, and B. pyrrocinia but was absent from B. multivorans, B.
      vietnamiensis, B. dolosa, and B. anthina. The zmpB gene was expressed, and ZmpB
      was purified from Escherichia coli by using the pPROEXHTa His(6) Tag expression
      system. ZmpB has a predicted preproenzyme structure typical of thermolysin-like
      proteases and is distantly related to Bacillus cereus bacillolysin. ZmpB was
      expressed as a 63-kDa preproenzyme precursor that was autocatalytically cleaved
      into mature ZmpB (35 kDa) and a 27-kDa prepropeptide. EDTA, 1,10-phenanthroline,
      and Zn(2+) cations inhibited ZmpB enzyme activity, indicating that it is a
      metalloprotease. ZmpB had proteolytic activity against alpha-1 proteinase
      inhibitor, alpha(2)-macrogobulin, type IV collagen, fibronectin, lactoferrin,
      transferrin, and immunoglobulins. B. cenocepacia zmpB and zmpA zmpB mutants had
      no proteolytic activity against casein and were less virulent in a rat agar bead
      chronic infection model, indicating that zmpB is involved in B. cenocepacia
      virulence. Expression of zmpB was regulated by both the CepIR and CciIR quorum
      sensing systems.

PMID- 16790783
TI  - Alpha-2,3-sialyltransferase enhances Neisseria gonorrhoeae survival during
      experimental murine genital tract infection.
AB  - The addition of host-derived sialic acid to Neisseria gonorrhoeae
      lipooligosaccharide is hypothesized to be an important mechanism by which
      gonococci evade host innate defenses. This hypothesis is based primarily on in
      vitro assays of complement-mediated and phagocytic killing. Here we report that a
      nonpolar alpha-2,3-sialyltransferase (lst) mutant of N. gonorrhoeae was
      significantly attenuated in its capacity to colonize the lower genital tract of
      17-beta estradiol-treated female BALB/c mice during competitive infection with
      the wild-type strain. Genetic complementation of the lst mutation restored
      recovery of the mutant to wild-type levels. Studies with B10.D2-HC(o)H2(d)H(2)
      T18c/OSN (C5-deficient) mice showed that attenuation of the lst mutant was not
      due to increased sensitivity to complement-mediated bacteriolysis, a result that
      is consistent with recently reported host restrictions in the complement cascade.
      However, Lst-deficient gonococci were killed more rapidly than sialylated wild
      type gonococci following intraperitoneal injection into normal mice, which is
      consistent with sialylation conferring protection against killing by
      polymorphonuclear leukocytes (PMNs). As reported for human PMNs, sialylated
      gonococci were more resistant to killing by murine PMNs, and sialylation led to
      reduced association with and induction of a weaker respiratory burst in PMNs from
      estradiol-treated mice. In summary, these studies suggest sialylation confers a
      survival advantage to N. gonorrhoeae in mice by increasing resistance to PMN
      killing. This report is the first direct demonstration that alpha-2,3
      sialyltransferase contributes to N. gonorrhoeae pathogenesis in an in vivo model.
      This study also validates the use of experimental murine infection to study
      certain aspects of gonococcal pathogenesis.

PMID- 16790785
TI  - Blastocystis ratti induces contact-independent apoptosis, F-actin rearrangement,
      and barrier function disruption in IEC-6 cells.
AB  - Blastocystis is an enteric protozoan purportedly associated with numerous
      clinical cases of diarrhea, flatulence, vomiting, and other gastrointestinal
      symptoms. Despite new knowledge of Blastocystis cell biology, genetic diversity,
      and epidemiology, its pathogenic potential remains controversial. Numerous
      clinical and epidemiological studies either implicate or exonerate the parasite
      as a cause of intestinal disease. Therefore, the aim of this study was to
      investigate the pathogenic potential of Blastocystis by studying the interactions
      of Blastocystis ratti WR1, an isolate of zoonotic potential, with a
      nontransformed rat intestinal epithelial cell line, IEC-6. Here, we report that
      B. ratti WR1 induces apoptosis in IEC-6 cells in a contact-independent manner.
      Furthermore, we found that B. ratti WR1 rearranges F-actin distribution,
      decreases transepithelial resistance, and increases epithelial permeability in
      IEC-6 cell monolayers. In addition, we found that the effects of B. ratti on
      transepithelial electrical resistance and epithelial permeability were
      significantly abrogated by treatment with metronidazole, an antiprotozoal drug.
      Our results suggest for the first time that Blastocystis-induced apoptosis in
      host cells and altered epithelial barrier function might play an important role
      in the pathogenesis of Blastocystis infections and that metronidazole has
      therapeutic potential in alleviating symptoms associated with Blastocystis.

PMID- 16790784
TI  - The type III pseudomonal exotoxin U activates the c-Jun NH2-terminal kinase
      pathway and increases human epithelial interleukin-8 production.
AB  - Microbial interactions with host cell signaling pathways are key determinants of
      the host cell response to infection. Many toxins secreted by bacterial type III
      secretion systems either stimulate or inhibit the host inflammatory response. We
      investigated the role of type III secreted toxins of the lung pathogen
      Pseudomonas aeruginosa in the inflammatory response of human respiratory
      epithelial cells to infection. Using bacteria with specific gene deletions, we
      found that interleukin-8 production by these cells was almost entirely dependent
      on bacterial type III secretion of exotoxin U (ExoU), a phospholipase, although
      other bacterial factors are involved. ExoU activated the c-Jun NH(2)-terminal
      kinase pathway, stimulating the phosphorylation and activation of mitogen
      activated kinase kinase 4, c-Jun NH(2)-terminal kinase, and c-Jun. This in turn
      increased levels of transcriptionally competent activator protein-1. Although
      this pathway was dependent on the lipase activity of ExoU, it was independent of
      cell death. Activation of mitogen-activated kinase signaling by ExoU in this
      fashion is a novel mechanism by which a bacterial product can initiate a host
      inflammatory response, and it may result in increased epithelial permeability and
      bacterial spread.

PMID- 16790786
TI  - Use of an Actinobacillus pleuropneumoniae multiple mutant as a vaccine that
      allows differentiation of vaccinated and infected animals.
AB  - Vaccination against Actinobacillus pleuropneumoniae is hampered by the lack of
      vaccines inducing reliable cross-serotype protection. In contrast, pigs surviving
      natural infection are at least partially protected from clinical symptoms upon
      reinfection with any serotype. Thus, we set out to construct an attenuated A.
      pleuropneumoniae live vaccine allowing the differentiation of vaccinated from
      infected animals (the DIVA concept) by successively deleting virulence-associated
      genes. Based on an A. pleuropneumoniae serotype 2 prototype live negative marker
      vaccine (W. Tonpitak, N. Baltes, I. Hennig-Pauka, and G.-F. Gerlach, Infect.
      Immun. 70:7120-7125, 2002), genes encoding three enzymes involved in anaerobic
      respiration and the ferric uptake regulator Fur were deleted, resulting in a
      highly attenuated sixfold mutant; this mutant was still able to colonize the
      lower respiratory tract and induced a detectable immune response. Upon a single
      aerosol application, this mutant provided significant protection from clinical
      symptoms upon heterologous infection with an antigenically distinct A.
      pleuropneumoniae serotype 9 challenge strain and allowed the serological
      discrimination between infected and vaccinated groups.

PMID- 16790787
TI  - Sialic acid-binding immunoglobulin-like lectin 7 mediates selective recognition
      of sialylated glycans expressed on Campylobacter jejuni lipooligosaccharides.
AB  - siglecs are a family of sialic-acid binding immunoglobulin-like lectins mostly
      expressed by cells of the immune system that have the potential to interact with
      sialylated glycans expressed not only on host cells but also on certain
      pathogens. Campylobacter jejuni is a common pathogen of humans that expresses
      surface lipooligosaccharides (LOS) that can be modified with ganglioside-like
      terminal structures in the core oligosaccharides. In this study, we examined the
      interaction of 10 siglecs with LOS purified from four different C. jejuni
      isolates expressing GM1-like, GD1a-like, GD3-like, and GT1a-like
      oligosaccharides. Of all siglecs examined, only Siglec-7 exhibited specific,
      sialic acid-dependent interactions with C. jejuni LOS in solid-phase binding
      assays. Binding was especially prominent with LOS from the HS:19(GM1(+) GT1a(+))
      isolate, with weaker binding with LOS from the HS:19(GD3(+)) isolate. Binding of
      Siglec-7 was also observed with intact bacteria expressing these LOS structures.
      Specific binding of HS:19(GM1(+) GT1a(+)) bacteria was demonstrated with Siglec-7
      expressed on transfected Chinese hamster ovary cells and with peripheral blood
      leukocytes, among which HS:19(GM1(+) GT1a(+)) bacteria bound selectively to both
      natural killer cells and monocytes which naturally express Siglec-7. These
      results raise the possibility that, in addition to their role in generating
      autoimmune antibody responses, C. jejuni LOS could interact with Siglec-7
      expressed by leukocytes, modulate the host-pathogen interaction, and contribute
      to the clinical outcome and the development of secondary complications such as
      Guillain-Barre syndrome.

PMID- 16790788
TI  - Expression of putative virulence factors of Escherichia coli O157:H7 differs in
      bovine and human infections.
AB  - Escherichia coli O157:H7 is a commensal organism in cattle, but it is a pathogen
      in humans. This differential expression of virulence suggests that specific
      virulence factors are regulated differently in human and bovine hosts. To test
      this hypothesis, relative real-time reverse transcription-PCR was used to relate
      the expression of several putative virulence genes (eae, espA, stx(2), rfbE,
      ehxA, and iha) to that of the "housekeeping" gene gnd during natural human and
      experimental bovine infection with E. coli O157:H7. We examined these genes in
      fecal samples from eight humans and four calves. iha and espA were significantly
      more expressed in bovine infections. rfbE and ehxA appeared to be more highly
      expressed in human infections, though these differences did not achieve
      statistical significance. Our results support the hypothesis that some virulence
      associated genes of O157:H7 are differentially expressed in a host-specific
      manner.

PMID- 16790789
TI  - A monoclonal antibody to Bacillus anthracis protective antigen defines a
      neutralizing epitope in domain 1.
AB  - Antibody (Ab) responses to Bacillus anthracis toxins are protective, but
      relatively few protective monoclonal antibodies (MAbs) have been reported.
      Protective antigen (PA) is essential for the action of B. anthracis lethal toxin
      (LeTx) and edema toxin. In this study, we generated two MAbs to PA, MAbs 7.5G and
      10F4. These MAbs did not compete for binding to PA, consistent with specificities
      for different epitopes. The MAbs were tested for their ability to protect a
      monolayer of cultured macrophages against toxin-mediated cytotoxicity. MAb 7.5G,
      the most-neutralizing MAb, bound to domain 1 of PA and reduced LeTx toxicity in
      BALB/c mice. Remarkably, MAb 7.5G provided protection without blocking the
      binding of PA or lethal factor or the formation of the PA heptamer complex.
      However, MAb 7.5G slowed the proteolytic digestion of PA by furin in vitro,
      suggesting a potential mechanism for Ab-mediated protection. These observations
      indicate that some Abs to domain 1 can contribute to host protection.

PMID- 16790790
TI  - Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire
      complement regulators C4b-binding protein and factor H.
AB  - Relapsing fever is a rapidly progressive and severe septic disease caused by
      certain Borrelia spirochetes. The disease is divided into two forms, i.e.,
      epidemic relapsing fever, caused by Borrelia recurrentis and transmitted by lice,
      and the endemic form, caused by several Borrelia species, such as B. duttonii,
      and transmitted by soft-bodied ticks. The spirochetes enter the bloodstream by
      the vector bite and live persistently in plasma even after the development of
      specific antibodies. This leads to fever relapses and high mortality and clearly
      indicates that the Borrelia organisms utilize effective immune evasion
      strategies. In this study, we show that the epidemic relapsing fever pathogen B.
      recurrentis and an endemic relapsing fever pathogen, B. duttonii, are serum
      resistant, i.e., resistant to complement in vitro. They acquire the host
      alternative complement pathway regulator factor H on their surfaces in a similar
      way to that of the less serum-resistant Lyme disease pathogen, B. burgdorferi
      sensu stricto. More importantly, the relapsing fever spirochetes specifically
      bind host C4b-binding protein, a major regulator of the antibody-mediated
      classical complement pathway. Both complement regulators retained their
      functional activities when bound to the surfaces of the spirochetes. In
      conclusion, this is the first report of complement evasion by Borrelia
      recurrentis and B. duttonii and the first report showing capture of C4b-binding
      protein by spirochetes.

PMID- 16790791
TI  - Alanine esters of enterococcal lipoteichoic acid play a role in biofilm formation
      and resistance to antimicrobial peptides.
AB  - Enterococcus faecalis is among the predominant causes of nosocomial infections.
      Surface molecules like d-alanine lipoteichoic acid (LTA) perform several
      functions in gram-positive bacteria, such as maintenance of cationic homeostasis
      and modulation of autolytic activities. The aim of the present study was to
      evaluate the effect of d-alanine esters of teichoic acids on biofilm production
      and adhesion, autolysis, antimicrobial peptide sensitivity, and opsonic killing.
      A deletion mutant of the dltA gene was created in a clinical E. faecalis isolate.
      The absence of d-alanine in the LTA of the dltA deletion mutant was confirmed by
      nuclear magnetic resonance spectroscopy. The wild-type strain and the deletion
      mutant did not show any significant differences in growth curve, morphology, or
      autolysis. However, the mutant produced significantly less biofilm when grown in
      the presence of 1% glucose (51.1% compared to that of the wild type); adhesion to
      eukaryotic cells was diminished. The mutant absorbed 71.1% of the opsonic
      antibodies, while absorption with the wild type resulted in a 93.2% reduction in
      killing. Sensitivity to several cationic antimicrobial peptides (polymyxin B,
      colistin, and nisin) was considerably increased in the mutant strain, confirming
      similar results from other studies of gram-positive bacteria. Our data suggest
      that the absence of d-alanine in LTA plays a role in environmental interactions,
      probably by modulating the net negative charge of the bacterial cell surface, and
      therefore it may be involved in the pathogenesis of this organism.

PMID- 16790792
TI  - Proinflammatory and immunomodulatory cytokine mRNA time course profiles in
      hamsters infected with a virulent variant of Leptospira interrogans.
AB  - In order to quantify in vivo the mRNAs of cytokines which play important roles in
      leptospirosis, we have developed quantitative real-time PCR assays for
      interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, tumor necrosis factor alpha (TNF
      alpha), gamma interferon (IFN-gamma), transforming growth factor beta, and two
      housekeeping genes (encoding beta-actin and hypoxanthine
      phosphoribosyltransferase). We used a lethal hamster model reflecting severe
      leptospirosis in humans. The LightCycler system was used to quantify the gene
      expression levels with the SYBR green I detection format using external standard
      curves for each target. We compared the expression levels of cytokine mRNA in the
      peripheral blood mononuclear cells of both control (uninfected) hamsters and
      Leptospira interrogans-inoculated hamsters from 1 to 24 h and then 1 to 4 days
      postinfection. In this kinetic study, there was pronounced expression of Th1
      cytokine mRNA (TNF-alpha, IFN-gamma, and IL-12), with transcripts being detected
      as early as 1 h postinfection. Expression of anti-inflammatory cytokines, such as
      IL-4 and IL-10, was prominent in delayed samples from 1 to 4 days postinfection
      in response to infection with Leptospira interrogans. Our data are the first to
      establish that pathogenic leptospires can stimulate in vivo the production of
      type 1 cytokines involved in cellular immunity by using this informative animal
      model. Measuring and assessing cytokine profiles may provide a useful method for
      accurate study of the mechanisms of anti-Leptospira immunity, indications of
      prognosis factors, and prospective evaluation of leptospirosis vaccine efficacy
      in humans.

PMID- 16790793
TI  - CD8 T cells require Bcl-3 for maximal gamma interferon production upon secondary
      exposure to antigen.
AB  - Adjuvant-induced survival of T cells after antigen activation correlates with
      increased expression of Bcl-3. Bcl-3 is an NF-kappaB/IkappaB family member and
      has been implicated in transcriptional regulation in several cell types. We
      tested the ability of mice deficient in Bcl-3 (Bcl-3 KO) to exhibit T-cell
      adjuvant-induced survival after challenge with the superantigen staphylococcal
      enterotoxin B (SEB), using lipopolysaccharide (LPS) as a natural adjuvant. These
      studies showed that Bcl-3 is required for secondary gamma interferon (IFN-gamma)
      production by CD8 T cells but not for adjuvant-induced survival effects.
      Specifically, wild-type and Bcl-3 KO mice exhibited comparable long-term
      increases in the Vbeta8(+) T-cell populations, indicating no lack of survival in
      response to adjuvant stimulation in the Bcl-3 KO activated T cells. Ectopic
      expression of the Bcl-3-related molecules IkappaBalpha, IkappaBbeta, and
      IkappaBepsilon in SEB-activated T cells increased survival during in vitro
      culture in the absence of adjuvant, suggesting that these IkappaB molecules could
      exert a survival function in antigen-activated T cells in place of Bcl-3.
      However, Vbeta8(+) CD8 T cells from SEB- plus LPS-treated Bcl-3 KO mice produced
      less IFN-gamma upon in vitro restimulation than Vbeta8(+) CD8 T cells from wild
      type mice. Therefore, Bcl-3 plays a unique role in the regulation of IFN-gamma
      production in this model system.

PMID- 16790794
TI  - Active genetic elements present in the locus of enterocyte effacement in
      Escherichia coli O26 and their role in mobility.
AB  - The locus of enterocyte effacement (LEE) is a large multigene chromosomal segment
      encoding gene products responsible for the generation of attaching and effacing
      lesions in many diarrheagenic Escherichia coli strains. A recently sequenced LEE
      harboring a pathogenicity island (PAI) from a Shiga toxin E. coli serotype O26
      strain revealed a LEE PAI (designated LEE O26) almost identical to that obtained
      from a rabbit-specific enteropathogenic O15:H- strain. LEE O26 comprises 59,540
      bp and is inserted at 94 min within the mature pheU tRNA locus. The LEE O26 PAI
      is flanked by two direct repeats of 137 and 136 bp (DR1 and DR2), as well as a
      gene encoding an integrase belonging to the P4 integrase family. We examined LEE
      O26 for horizontal gene transfer. By generating mini-LEE plasmids harboring only
      DR1 or DR2 with or without the integrase-like gene, we devised a simple assay to
      examine recombination processes between these sequences. Recombination was shown
      to be integrase dependent in a DeltarecA E. coli K-12 strain background.
      Recombinant plasmids harboring a single direct repeat cloned either with or
      without the LEE O26 integrase gene were found to insert within the chromosomal
      pheU locus of E. coli K-12 strains with equal efficiency, suggesting that an
      endogenous P4-like integrase can substitute for this activity. An integrase with
      strong homology to the LEE O26 integrase was detected on the K-12 chromosome
      associated with the leuX tRNA locus at 97 min. Strains deleted for this integrase
      demonstrated a reduction in the insertion frequency of plasmids harboring only
      the DR into the pheU locus. These results provide strong evidence that LEE
      harboring elements are indeed mobile and suggest that closely related integrases
      present on the chromosome of E. coli strains contribute to the dynamics of PAI
      mobility.

PMID- 16790795
TI  - Identification and characterization of an antigen I/II family protein produced by
      group A Streptococcus.
AB  - Group A Streptococcus (GAS) is a gram-positive human bacterial pathogen that
      causes infections ranging in severity from pharyngitis to life-threatening
      invasive disease, such as necrotizing fasciitis. Serotype M28 strains are
      consistently isolated from invasive infections, particularly puerperal sepsis, a
      severe infection that occurs during or after childbirth. We recently sequenced
      the genome of a serotype M28 GAS strain and discovered a novel 37.4-kb foreign
      genetic element designated region of difference 2 (RD2). RD2 is similar in gene
      content and organization to genomic islands found in group B streptococci (GBS),
      the major cause of neonatal infections. RD2 encodes seven proteins with
      conventional gram-positive secretion signal sequences, six of which have not been
      characterized. Herein, we report that one of these six proteins (M28_Spy1325;
      Spy1325) is a member of the antigen I/II family of cell surface-anchored
      molecules produced by oral streptococci. PCR and DNA sequence analysis found that
      Spy1325 is very well conserved in GAS strains of distinct M protein serotypes. As
      assessed by real-time TaqMan quantitative PCR, the Spy1325 gene was expressed in
      vitro, and Spy1325 protein was present in culture supernatants and on the GAS
      cell surface. Western immunoblotting and enzyme-linked immunosorbent assays
      indicated that Spy1325 was produced by GAS in infected mice and humans.
      Importantly, the immunization of mice with recombinant Spy1325 fragments
      conferred protection against GAS-mediated mortality. Similar to other antigen
      I/II proteins, recombinant Spy1325 bound purified human salivary agglutinin
      glycoprotein. Spy1325 may represent a shared virulence factor among GAS, GBS, and
      oral streptococci.

PMID- 16790796
TI  - Role of Porphyromonas gingivalis FeoB2 in metal uptake and oxidative stress
      protection.
AB  - Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized
      periodontopathogen. It exhibits a high degree of aerotolerance and is able to
      survive in host cells, indicating that efficient oxidative stress protection
      mechanisms must be present in this organism. Manganese homeostasis plays a major
      role in oxidative stress protection in a variety of organisms; however, the
      transport and role of this metal in P. gingivalis is not well understood.
      Analysis of the genome of P. gingivalis W83 revealed the presence of two genes
      encoding homologs of a ferrous iron transport protein, FeoB1 and FeoB2. FeoB2 has
      been implicated in manganese accumulation in P. gingivalis. We sought to
      determine the role of the FeoB2 protein in metal transport as well as its
      contribution to resistance to oxygen radicals. Quantitative reverse transcriptase
      PCR analyses demonstrated that expression of feoB2 is induced in the presence of
      oxygen. The role of FeoB2 was investigated using an isogenic mutant strain
      deficient in the putative transporter. We characterized the FeoB2-mediated metal
      transport using (55)Fe(2+) and (54)Mn(2+). The FeoB2-deficient mutant had
      dramatically reduced rates of manganese uptake (0.028 pmol/min/10(7) bacteria)
      compared with the parental strain (0.33 pmol/min/10(7) bacteria) (after 20 min of
      uptake using 50 nM of (54)Mn(2+)). The iron uptake rates, however, were higher in
      the mutant strain (0.75 pmol/min/10(7) bacteria) than in the wild type (0.39
      pmol/min/10(7) bacteria). Interestingly, reduced survival rates were also noted
      for the mutant strain after exposure to H(2)O(2) and to atmospheric oxygen
      compared to the parental strain cultured under the same conditions. In addition,
      in vitro infection of host cells with the wild type, the FeoB2-deficient mutant,
      and the same-site revertant revealed that the mutant had a significantly
      decreased capability for intracellular survival in the host cells compared to the
      wild-type strain. Our results demonstrate that feoB2 encodes a major manganese
      transporter required for protection of the bacterium from oxidative stress
      generated by atmospheric oxygen and H(2)O(2). Furthermore, we show that FeoB2 and
      acquisition of manganese are required for intracellular survival of P. gingivalis
      in host cells.

PMID- 16790797
TI  - Identification of Francisella tularensis genes affected by iron limitation.
AB  - Cells of an attenuated live vaccine strain (LVS) of F. tularensis grown under
      iron-restricted conditions were found to contain increased quantities of several
      proteins relative to cells of this same strain grown under iron-replete
      conditions. Mass spectrometric analysis identified two of these proteins as IglC
      and PdpB, both of which are encoded by genes located in a previously identified
      pathogenicity island in F. tularensis LVS. Regions with homology to the consensus
      Fur box sequence were located immediately in front of the iglC and pdpB open
      reading frames (ORFs), and in silico analysis of the F. tularensis Schu4 genome
      detected a number of predicted 5' untranslated regions that contained putative
      Fur boxes. The putative Fur box preceding Francisella iron-regulated gene A
      (figA) had the highest degree of identity with the consensus Fur box sequence.
      DNA microarray analysis showed that nearly 80 of the genes in the F. tularensis
      LVS genome were up- or down-regulated at least twofold under iron-restricted
      growth conditions. When tested for possible siderophore production by means of
      the Chrome Azurol S assay, a wild-type F. novicida strain produced a large
      reaction zone whereas its figA mutant produced very little reactivity in this
      assay. In addition, a cross-feeding experiment demonstrated that this siderophore
      like activity produced by the wild-type F. novicida strain could enhance the
      ability of the F. novicida figA mutant to grow under iron-restricted conditions.
      This study provides the first identification of iron-regulated genes in F.
      tularensis LVS and evidence for the production of a siderophore-like molecule by
      F. novicida.

PMID- 16790798
TI  - Identification of Pseudomonas aeruginosa genes involved in virulence and
      anaerobic growth.
AB  - Pseudomonas aeruginosa is a gram-negative, opportunistic pathogen and a
      significant cause of acute and chronic infections in patients with compromised
      host defenses. Evidence suggests that within infections P. aeruginosa encounters
      oxygen limitation and exists in microbial aggregates known as biofilms. However,
      there is little information that describes genes involved in anaerobic growth of
      P. aeruginosa and their association with virulence of this pathogen. To identify
      genes required for anaerobic growth, random transposon (Tn) mutagenesis was used
      to screen for mutants that demonstrated the inability to grow anaerobically using
      nitrate as a terminal electron acceptor. Of approximately 35,000 mutants
      screened, 57 mutants were found to exhibit no growth anaerobically using nitrate.
      Identification of the genes disrupted by the Tn revealed 24 distinct loci
      required for anaerobic growth on nitrate, including several genes not previously
      associated with anaerobic growth of P. aeruginosa. Several of these mutants were
      capable of growing anaerobically using nitrite and/or arginine, while five
      mutants were unable to grow anaerobically under any of the conditions tested.
      Three mutants were markedly attenuated in virulence in the lettuce model of P.
      aeruginosa infection. These studies have identified novel genes important for
      anaerobic growth and demonstrate that anaerobic metabolism influences virulence
      of P. aeruginosa.

PMID- 16790799
TI  - Exploitation of the endocytic pathway by Orientia tsutsugamushi in
      nonprofessional phagocytes.
AB  - Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate
      intracellular bacterium that requires the exploitation of the endocytic pathway
      in the host cell. We observed the localization of O. tsutsugamushi with clathrin
      or adaptor protein 2 within 30 min after the infection of nonprofessional
      phagocytes. We have further confirmed that the infectivity of O. tsutsugamushi is
      significantly reduced by drugs that block clathrin-mediated endocytosis but not
      by filipin III, an inhibitor that blocks caveola-mediated endocytosis. In the
      present study, with a confocal microscope, O. tsutsugamushi was sequentially
      colocalized with the early and late endosomal markers EEA1 and LAMP2,
      respectively, within 1 h after infection. The colocalization of O. tsutsugamushi
      organisms with EEA1 and LAMP2 gradually disappeared until 2 h postinfection, and
      then free O. tsutsugamushi organisms were found in the cytoplasm. When the
      acidification of endocytic vesicles was blocked by treating the cells with
      NH(4)Cl or bafilomycin A, the escape of O. tsutsugamushi organisms from the
      endocytic pathway was severely impaired, and the infectivity of O. tsutsugamushi
      was drastically reduced. To our knowledge, this is the first report that the
      invasion of O. tsutsugamushi is dependent on the clathrin-dependent endocytic
      pathway and the acidification process of the endocytic vesicles in
      nonprofessional phagocytes.

PMID- 16790800
TI  - cDNA microarray analysis of host-pathogen interactions in a porcine in vitro
      model for Toxoplasma gondii infection.
AB  - Toxoplasma gondii induces the expression of proinflammatory cytokines,
      reorganizes organelles, scavenges nutrients, and inhibits apoptosis in infected
      host cells. We used a cDNA microarray of 420 annotated porcine expressed sequence
      tags to analyze the molecular basis of these changes at eight time points over a
      72-hour period in porcine kidney epithelial (PK13) cells infected with T. gondii.
      A total of 401 genes with Cy3 and Cy5 spot intensities of >/=500 were selected
      for analysis, of which 263 (65.6%) were induced >/=2-fold (expression ratio,
      >/=2.0; P </= 0.05 [t test]) over at least one time point and 48 (12%) were
      significantly down-regulated. At least 12 functional categories of genes were
      modulated (up- or down-regulated) by T. gondii. The majority of induced genes
      were clustered as transcription, signal transduction, host immune response,
      nutrient metabolism, and apoptosis related. The expression of selected genes
      altered by T. gondii was validated by quantitative real-time reverse
      transcription-PCR. These results suggest that significant changes in gene
      expression occur in response to T. gondii infection in PK13 cells, facilitating
      further analysis of host-pathogen interactions in toxoplasmosis in a secondary
      host.

PMID- 16790801
TI  - Low-phosphate-dependent invasion resembles a general way for Neisseria
      gonorrhoeae to enter host cells.
AB  - Obligate human-pathogenic Neisseria gonorrhoeae expresses numerous variant
      surface proteins mediating adherence to and invasion of target cells. The
      invariant major outer membrane porin PorB of serotype A (P.IA) gonococci triggers
      invasion into Chang cells only if the medium is devoid of phosphate. Since
      gonococci expressing PorB(IA) are frequently isolated from patients with severe
      disseminating infections, the interaction initiated by the porin may be of major
      relevance for the development of this serious disease. Here, we investigated the
      low-phosphate-dependent invasion and compared it to the well-known pathways of
      entry initiated by Opa proteins. P.IA-triggered invasion requires clathrin-coated
      pit formation and the action of actin and Rho GTPases. However, in contrast to
      Opa-initiated invasion via heparan sulfate proteoglycans, microtubules, acidic
      sphingomyelinase, phosphatidylinositol 3-kinase, and myosin light chain kinase
      are not involved in this entry pathway. Nor are Src kinases required, as they are
      in invasion, e.g., via the CEACAM3 receptor. Invasion by PorB(IA) occurs in a
      wide spectrum of cell types, such as primary human epithelial and endothelial
      cells and in cancer cells of human and animal origin. Low-phosphate-dependent
      invasion is thus a pathway of gonococcal entry distinct from Opa-mediated
      invasion.

PMID- 16790802
TI  - Toxoplasma gondii inhibits toll-like receptor 4 ligand-induced mobilization of
      intracellular tumor necrosis factor alpha to the surface of mouse peritoneal
      neutrophils.
AB  - Neutrophils are well-known to rapidly respond to infection through chemotactic
      infiltration at sites of inflammation, followed by rapid release of microbicidal
      molecules, chemokines, and proinflammatory cytokines. For tumor necrosis factor
      alpha (TNF-alpha), we recently found that neutrophils contain intracellular pools
      of the cytokine and display the capacity to upregulate transcriptional activity
      of the gene during lipopolysaccharide (LPS) stimulation. We now show that
      triggering of mouse peritoneal neutrophils with Toll-like receptor 2 (TLR2),
      TLR4, and TLR9 ligands, but not ligands of TLR3, induces upregulation of surface
      membrane TNF-alpha. However, neutrophils infected with the protozoan Toxoplasma
      gondii displayed an inability to respond fully in terms of TLR ligand-induced
      increases in membrane TNF-alpha expression. Infected neutrophils failed to
      display decreased levels of intracellular TNF-alpha upon LPS exposure. In
      contrast to intermediate inhibitory effects in nontreated neutrophils, T. gondii
      induced a complete blockade in LPS-induced surface TNF-alpha expression in the
      presence of the protein synthesis inhibitor cycloheximide. Despite these
      inhibitory effects, the parasite did not affect LPS-induced upregulation of TNF
      alpha gene transcription. Collectively, the results show that Toxoplasma prevents
      TLR ligand-triggered mobilization of TNF-alpha to the neutrophil surface,
      revealing a novel immunosuppressive activity of the parasite.

PMID- 16790803
TI  - Phenotypic and functional characterization of vaginal dendritic cells in a rat
      model of Candida albicans vaginitis.
AB  - This study analyzes the phenotype of vaginal dendritic cells (VDCs), their
      antigenic presentation and activation of T-cell cytokine secretion, and their
      protective role in a rat model of Candida vaginitis. Histological observation
      demonstrated a significant accumulation of OX62(+) VDCs in the mucosal epithelium
      of Candida albicans-infected rats at the third round of infection. We identified
      two subsets of OX62(+) VDCs differing in the expression of CD4 molecule in both
      noninfected and Candida-infected rats. The OX62(+) CD4(+) subset of VDCs
      displayed a lymphoid cell-like morphology and expressed the T-cell antigen CD5,
      whereas the OX62(+) CD4(-) VDC subset exhibited a myeloid morphology and was CD5
      negative. Candida infection resulted in VDC maturation with enhanced expression
      of CD80 and CD134L on both CD4(+) and CD4(-) VDC subsets at 2 and 6 weeks after
      Candida infection. CD5(-) CD4(-) CD86(-) CD80(-) CD134L(+) VDCs from infected,
      but not noninfected, rats spontaneously released large amounts of interleukin-12
      (IL-12) and tumor necrosis factor alpha, whereas all VDC subsets released
      comparable levels of IL-10 and IL-2 cytokines. Furthermore, OX62(+) VDCs from
      infected rats primed naive CD4(+) T-cell proliferation and release of cytokines,
      including gamma interferon, IL-2, IL-6, and IL-10, in response to staphylococcal
      enterotoxin B stimulation in vitro. Adoptive transfer of highly purified OX62(+)
      VDCs from infected rats induced a significant acceleration of fungal clearance
      compared with that in rats receiving naive VDCs, suggesting a protective role of
      VDCs in the anti-Candida mucosal immunity. Finally, VDC-mediated protection was
      associated with their ability to rapidly migrate to the vaginal mucosa and lymph
      nodes, as assessed by adoptive transfer of OX62(+) VDCs labeled with 5 (and 6-)
      carboxyfluorescein diacetate succinimidyl ester.

PMID- 16790804
TI  - Genetically determined susceptibility to tuberculosis in mice causally involves
      accelerated and enhanced recruitment of granulocytes.
AB  - Classical twin studies and recent linkage analyses of African populations have
      revealed a potential involvement of host genetic factors in susceptibility or
      resistance to Mycobacterium tuberculosis infection. In order to identify the
      candidate genes involved and test their causal implication, we capitalized on the
      mouse model of tuberculosis, since inbred mouse strains also differ substantially
      in their susceptibility to infection. Two susceptible and two resistant mouse
      strains were aerogenically infected with 1,000 CFU of M. tuberculosis, and the
      regulation of gene expression was examined by Affymetrix GeneChip U74A array with
      total lung RNA 2 and 4 weeks postinfection. Four weeks after infection, 96 genes,
      many of which are involved in inflammatory cell recruitment and activation, were
      regulated in common. One hundred seven genes were differentially regulated in
      susceptible mouse strains, whereas 43 genes were differentially expressed only in
      resistant mice. Data mining revealed a bias towards the expression of genes
      involved in granulocyte pathophysiology in susceptible mice, such as an
      upregulation of those for the neutrophil chemoattractant LIX (CXCL5), interleukin
      17 receptor, phosphoinositide kinase 3 delta, or gamma interferon-inducible
      protein 10. Following M. tuberculosis challenge in both airways or peritoneum,
      granulocytes were recruited significantly faster and at higher numbers in
      susceptible than in resistant mice. When granulocytes were efficiently depleted
      by either of two regimens at the onset of infection, only susceptible mice
      survived aerosol challenge with M. tuberculosis significantly longer than control
      mice. We conclude that initially enhanced recruitment of granulocytes contributes
      to susceptibility to tuberculosis.

PMID- 16790805
TI  - Hybridoma passage in vitro may result in reduced ability of antimannan antibody
      to protect against disseminated candidiasis.
AB  - We previously reported the enhanced resistance of monoclonal antibodies B6.1 (an
      immunoglobulin M [IgM]) and C3.1 (an IgG3) against experimental candidiasis. Both
      MAbs recognize the same fungal epitope. We have since found that a highly
      passaged B6.1 hybridoma (hp-B6.1) resulted in antibody that has little protective
      potential. The potential clinical applicability of the antibody and our interest
      in understanding antibody protection against candidiasis led us to investigate an
      explanation for this phenomenon. Antibody genetic structure of hp-B6.1, the
      original hybridoma clone (ori-B6.1) stored frozen since 1995, a subclone of hp
      B6.1 that produces protective antibody, the IgG3-producing hybridoma, and a
      nonprotective IgG1-producing hybridoma were compared. Variable region gene
      sequences of heavy (V(H)) and light chains showed genetic instability of V(H)
      chains with only the hp-B6.1; the V(H) sequences from ori-B6.1 and the subclone
      were, however, identical. Activation-induced cytidine deaminase levels were
      greatest in the B6.1 hybridomas, which may explain the instability. The constant
      region CH3 domain remained unchanged, implying normal N-glycation and complement
      fixing potential, and antibody binding affinities appeared unchanged. Complement
      fixation assays surprisingly showed that ori-B6.1 antibody fixes C3 more rapidly
      than does hp-B6.1 antibody. The V(H) region primary structure may affect
      complement activation, which could explain our result. Indeed, antibody from the
      hp-B6.1 subclone fixed complement like antibody from ori-B6.1. These results show
      that the greatest protection occurs when antimannan antibodies possess the dual
      abilities of recognizing the appropriate carbohydrate epitope and rapidly fixing
      complement; loss of the latter property results in the loss of protective
      potential by the antibody.

PMID- 16790806
TI  - The Yersinia enterocolitica invasin protein promotes major histocompatibility
      complex class I- and class II-restricted T-cell responses.
AB  - Yersinia enterocolitica invasin (Inv) protein confers internalization into and
      expression of proinflammatory cytokines by host cells. Both events require
      binding of Inv to beta1 integrins, which initiates signaling cascades including
      activation of focal adhesion complexes, Rac1, mitogen-activated protein kinase,
      and NF-kappaB. Here we tested whether Inv might be suitable as a delivery
      molecule and adjuvant if used as a component of a vaccine. For this purpose,
      hybrid proteins composed of Inv and ovalbumin (OVA) were prepared, applied as a
      coating to microparticles, and used for vaccination. Fusion of OVA to Inv did not
      significantly disturb the ability of Inv to promote host cell binding,
      internalization, and interleukin-8 (IL-8) secretion when applied as a coating to
      microparticles. The microparticles were used for vaccination of mice adoptively
      transferred with OVA-specific T cells from OT-1 or DO11.10 mice. Administration
      of OVA-Inv-coated microparticles induced OVA-specific T-cell responses. OVA
      specific CD4 T cells produced both gamma interferon (IFN-gamma) and IL-4 as
      determined by enzyme-linked immunosorbent assay. Likewise, pronounced OVA
      specific CD8 T-cell responses associated with IFN-gamma production were observed.
      Together, these results suggest that Inv might be an attractive tool in
      vaccination as it confers both host cell uptake and adjuvant activity by
      engagement of beta1 integrins of host cells, which leads to CD4 as well as CD8 T
      cell responses.

PMID- 16790807
TI  - A set of glycosylphosphatidyl inositol-anchored membrane proteins of Plasmodium
      falciparum is refractory to genetic deletion.
AB  - Targeted gene disruption has proved to be a powerful approach for studying the
      function of important ligands involved in erythrocyte invasion by the
      extracellular merozoite form of the human malaria parasite, Plasmodium
      falciparum. Merozoite invasion proceeds via a number of seemingly independent
      alternate pathways, such that entry can proceed with parasites lacking particular
      ligand-receptor interactions. To date, most focus in this regard has been on
      single-pass (type 1) membrane proteins that reside in the secretory organelles.
      Another class of merozoite proteins likely to include ligands for erythrocyte
      receptors are the glycosylphosphatidyl inositol (GPI)-anchored membrane proteins
      that coat the parasite surface and/or reside in the apical organelles. Several of
      these are prominent vaccine candidates, although their functions remain unknown.
      Here, we systematically attempted to disrupt the genes encoding seven of the
      known GPI-anchored merozoite proteins of P. falciparum by using a double
      crossover gene-targeting approach. Surprisingly, and in apparent contrast to
      other merozoite antigen classes, most of the genes (six of seven) encoding GPI
      anchored merozoite proteins are refractory to genetic deletion, with the
      exception being the gene encoding merozoite surface protein 5 (MSP-5). No
      distinguishable growth rate or invasion pathway phenotype was detected for the
      msp-5 knockout line, although its presence as a surface-localized protein was
      confirmed.

PMID- 16790809
TI  - The animal pathogen-like type III secretion system is required for the
      intracellular survival of Burkholderia mallei within J774.2 macrophages.
AB  - Burkholderia mallei is a highly infectious gram-negative pathogen and is the
      causative agent of human and animal glanders. By generating polar mutations
      (disruption of bsaQ and bsaZ) in the B. mallei ATCC 23344 animal pathogen-like
      type III secretion system (TTS), we demonstrate that this bacterial protein
      delivery system is required for intracellular growth of B. mallei in J774.2
      cells, formation of macrophage membrane protrusions, actin polymerization, and
      phagosomal escape. These findings suggest that TTS plays a role in the
      intracellular trafficking of B. mallei and may facilitate cell-to-cell spread via
      actin-based motility.

PMID- 16790808
TI  - Effect of a CD4-depleting antibody on the development of Cryptococcus neoformans
      induced allergic bronchopulmonary mycosis in mice.
AB  - Allergic bronchopulmonary mycosis (ABPM) is a hypersensitivity lung disease in
      which fungal colonization is accompanied by an allergic response to the fungus.
      Using a mouse model of ABPM caused by Cryptococcus neoformans infection of
      C57BL/6 mice, the goal of the present studies was to determine the effect of the
      CD4-depleting monoclonal antibody GK1.5 on the development of the allergic
      responses seen during active fungal infection. These results would provide
      insight into the role of CD4(+) T cells in this disease. Our results show that
      GK1.5 treatment resulted in attenuation of pulmonary inflammation and
      eosinophilia in these animals. These mice also had reduced T2 cytokine production
      and no serum immunoglobulin E production. Absence of CD4(+) T cells did not
      affect recruitment of CD8(+) T cells to the site of infection; however, the
      numbers of CD19(+) B cells were severely reduced in the lungs of CD4(+) T-cell
      depleted animals. We also examined changes in the pulmonary architecture and
      found that depletion of CD4(+) T cells was associated with a significant
      reduction in mucus production and goblet cell metaplasia in these mice.
      Interestingly, attenuation of Th2 responses in CD4(+) T-cell-depleted animals did
      not increase the fungal load in their lungs. We also compared development of ABPM
      in young and mature mice and did not find any differences at any of the time
      points. Overall, our results show that depletion of CD4(+) T cells prevents the
      development of Th2 responses seen during ABPM.

PMID- 16790810
TI  - Cell activation by ligands of the toll-like receptor and interleukin-1 receptor
      family depends on the function of the large-conductance potassium channel MaxiK
      in human macrophages.
AB  - Performing patch-clamp experiments on human macrophages, we show that the K(+)
      channel MaxiK is activated by lipopolysaccharide, peptidoglycan, and interleukin
      1. Cytokine production initiated by several Toll-like receptor (TLR) ligands and
      by interleukin-1 is inhibited by MaxiK blockade. This provides evidence for
      functional association of the MaxiK channel and TLR signaling complexes.

PMID- 16790811
TI  - Baculovirus-expressed constructs induce immunoglobulin G that recognizes VAR2CSA
      on Plasmodium falciparum-infected erythrocytes.
AB  - We raised specific antisera against recombinant VAR2CSA domains produced in
      Escherichia coli and in insect cells. All were reactive in enzyme-linked
      immunosorbent assay, but only insect cell-derived constructs induced
      immunoglobulin G (IgG) that was reactive with native VAR2CSA on the surface of
      infected erythrocytes. Our data show that five of the six VAR2CSA Duffy-binding
      like domains are surface exposed and that induction of surface-reactive VAR2CSA
      specific IgG depends critically upon antigen conformation. These findings have
      implications for the development of vaccines against pregnancy-associated
      Plasmodium falciparum malaria.

PMID- 16790812
TI  - Characterization of a novel porin involved in systemic Yersinia enterocolitica
      infection.
AB  - Yersinia enterocolitica is an enteric pathogen capable of causing systemic
      disease in a murine model. We have identified a novel protein, systemic factor
      protein A (SfpA), conserved in other pathogenic bacteria that is involved in
      systemic disease. Analysis of bacterial colonization revealed that a DeltasfpA
      strain is defective in mesenteric lymph node colonization. Bioinformatics and
      functional studies suggest that SfpA is a porin.

PMID- 16790813
TI  - Role of calcineurin in stress resistance, morphogenesis, and virulence of a
      Candida albicans wild-type strain.
AB  - By generating a calcineurin mutant of the Candida albicans wild-type strain
      SC5314 with the help of a new recyclable dominant selection marker, we confirmed
      that calcineurin mediates tolerance to a variety of stress conditions but is not
      required for the ability of C. albicans to switch to filamentous growth in
      response to hypha-inducing environmental signals. While calcineurin was essential
      for virulence of C. albicans in a mouse model of disseminated candidiasis,
      deletion of CMP1 did not significantly affect virulence during vaginal or
      pulmonary infection, demonstrating that the requirement for calcineurin for a
      successful infection depends on the host niche.

PMID- 16790814
TI  - Responses to Leishmania donovani in mice deficient in interleukin-12 (IL-12), IL
      12/IL-23, or IL-18.
AB  - Interleukin-12 (IL-12) orchestrates acquired resistance in intracellular
      Leishmania donovani infection in the liver, inducing gamma interferon and, in
      turn, macrophage activation and parasite killing. Nevertheless, testing in IL-18(
      /-) mice compared to wild-type mice and in IL-12p40(-/-) compared to IL-12p35(-/
      ) mice also suggested both early-acting (IL-18) and late-acting (IL-23)
      antileishmanial effects independent of IL-12.

PMID- 16790815
TI  - Genotypic profile of the outer membrane proteins BabA and BabB in clinical
      isolates of Helicobacter pylori.
AB  - Helicobacter pylori BabA is the ABO blood group antigen binding adhesin, which
      has a closely related paralogue (BabB) whose function is unknown. PCR and DNA
      sequence analysis showed extensive genotypic diversity in babA and babB across
      different strains, as well as within a strain colonizing an individual patient.
      We hypothesize that diverse profiles of babA and babB reflect selective pressures
      for adhesion, which may differ across different hosts and within an individual
      over time.

PMID- 16790816
TI  - Role of tumor necrosis factor alpha in development of immunity against
      Cryptosporidium parvum infection.
AB  - Tumor necrosis factor (TNF-alpha) significantly reduced Cryptosporidium parvum
      development in a murine enterocyte cell line, and a key mechanism of action
      appeared to be inhibition of parasite invasion. However, TNF-alpha-deficient mice
      controlled infection as effectively as wild-type mice. This suggests that TNF
      alpha might have only a redundant role for establishing immunity against C.
      parvum.

PMID- 16790817
TI  - Stabilization of a plasmid coding for a heterologous antigen in Salmonella
      enterica serotype typhi vaccine strain CVD908-htrA by using site-specific
      recombination.
AB  - A gene cassette incorporating the crs-rsd site-specific recombination system from
      the Salmonella enterica subsp. enterica serovar Dublin virulence plasmid improved
      the inheritance in S. enterica serotype Typhi strain CVD908-htrA of a multicopy
      plasmid expression vector. Use of this recombination cassette may improve
      expression of heterologous antigens from multicopy plasmid expression vectors in
      attenuated bacterial vaccine strains.

PMID- 16790818
TI  - Transient neonatal Cryptosporidium parvum infection triggers long-term jejunal
      hypersensitivity to distension in immunocompetent rats.
AB  - In 5-day-old immunocompetent Sprague-Dawley rats infected with either 10(2) or
      10(5) Cryptosporidium parvum oocysts, transient infection resulted 120 days later
      in increased cardiovascular depressor response to jejunal distension and jejunal
      myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal
      sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant
      further evaluation of the role of early cryptosporidiosis in the development of
      chronic inflammatory gut conditions.

PMID- 16790819
TI  - A personal history: social medicine in a South African setting, 1952-5. Part 1:
      The shape of ideas forged in the second world war.

PMID- 16790820
TI  - Social medicine: national and international transfer of ideas.

PMID- 16790821
TI  - Things that kept coming to mind while thinking through Susser's South African
      memoir.

PMID- 16790822
TI  - The health society: the need for a theory.

PMID- 16790823
TI  - Developed countries should be the focus for effectively reducing chronic disease.

PMID- 16790824
TI  - A guide and glossary on post-positivist theory building for population health.
AB  - This guide and glossary focuses on the role of theory and conceptual models
      within population health research. Upon discussing the critical need for theory
      in conducting interdisciplinary research, it provides strategies for crafting
      theories that can be empirically tested and a glossary of theory building terms
      that are useful for guiding research. In addition to general concepts, the
      glossary includes some terminology commonly found in the social sciences, whose
      well established traditions and practices of formal theory building may be
      particularly informative for epidemiologists and other population health
      researchers who have minimal formal social science training, but study social
      factors in their research.

PMID- 16790825
TI  - Whose theory is it anyway?

PMID- 16790826
TI  - Speaking theoretically about population health.

PMID- 16790827
TI  - Where does new theory come from?

PMID- 16790828
TI  - Theory building on the high seas of population health: Love Boat, Mutiny on the
      Bounty, or Poseidon Adventure?

PMID- 16790829
TI  - Estimating causal effects from epidemiological data.
AB  - In ideal randomised experiments, association is causation: association measures
      can be interpreted as effect measures because randomisation ensures that the
      exposed and the unexposed are exchangeable. On the other hand, in observational
      studies, association is not generally causation: association measures cannot be
      interpreted as effect measures because the exposed and the unexposed are not
      generally exchangeable. However, observational research is often the only
      alternative for causal inference. This article reviews a condition that permits
      the estimation of causal effects from observational data, and two methods --
      standardisation and inverse probability weighting -- to estimate population
      causal effects under that condition. For simplicity, the main description is
      restricted to dichotomous variables and assumes that no random error attributable
      to sampling variability exists. The appendix provides a generalisation of inverse
      probability weighting.

PMID- 16790830
TI  - Green space, urbanity, and health: how strong is the relation?
AB  - STUDY OBJECTIVES: To investigate the strength of the relation between the amount
      of green space in people's living environment and their perceived general health.
      This relation is analysed for different age and socioeconomic groups.
      Furthermore, it is analysed separately for urban and more rural areas, because
      the strength of the relation was expected to vary with urbanity. DESIGN: The
      study includes 250 782 people registered with 104 general practices who filled in
      a self administered form on sociodemographic background and perceived general
      health. The percentage of green space (urban green space, agricultural space,
      natural green space) within a one kilometre and three kilometre radius around the
      postal code coordinates was calculated for each household. METHODS: Multilevel
      logistic regression analyses were performed at three levels-that is, individual
      level, family level, and practice level-controlled for sociodemographic
      characteristics. MAIN RESULTS: The percentage of green space inside a one
      kilometre and a three kilometre radius had a significant relation to perceived
      general health. The relation was generally present at all degrees of urbanity.
      The overall relation is somewhat stronger for lower socioeconomic groups.
      Elderly, youth, and secondary educated people in large cities seem to benefit
      more from presence of green areas in their living environment than other groups
      in large cities. CONCLUSIONS: This research shows that the percentage of green
      space in people's living environment has a positive association with the
      perceived general health of residents. Green space seems to be more than just a
      luxury and consequently the development of green space should be allocated a more
      central position in spatial planning policy.

PMID- 16790831
TI  - Validity of self reported diagnoses of cancer in a major Spanish prospective
      cohort study.
AB  - INTRODUCTION: This study aims to assess the validity of self reported diagnoses
      of cancer by persons recruited for the Spanish EPIC (European prospective
      investigation into cancer and nutrition) cohort study and to identify variables
      associated with correctly reporting a diagnosis of cancer. METHODS: 41 440
      members of EPIC were asked at the time of recruitment whether they had been
      diagnosed with cancer and the year of diagnosis and site. The process of
      validating self reported diagnoses of cancer included comparison of the cohort
      database with the data from the population based cancer registries. Cancer
      diagnostic validity tests were calculated. The association between a correct
      report and certain sociodemographic, tumour related, or health related variables
      were analysed by logistic regression. RESULTS: The overall sensitivity of self
      reported diagnoses of cancer is low (57.5%; 95% CI: 51.9 to 63.0), the highest
      values being shown by persons with a higher level of education or with a family
      history of cancer and the lowest values by smokers. Breast and thyroid cancers
      are those with the highest diagnostic validity and uterus, bladder, and colon
      rectum those with the lowest. In both sexes the variables showing a significant
      association with a correct report of cancer are: higher education level, number
      of previous pathologies, invasive tumour, and, in women, a history of
      gynaecological surgery. CONCLUSIONS: The overall sensitivity of self reported
      diagnoses of cancer is comparatively low and it is not recommended in
      epidemiological studies for identifying tumours. However, self reported diagnoses
      might be highly valid for certain tumour sites, malignant behaviour, and average
      to high levels of education.

PMID- 16790832
TI  - Uptake of screening for breast cancer in patients with mental health problems.
AB  - OBJECTIVES: Mental illness is associated with physical illness and mortality from
      a variety of causes including cancer. There is little information on screening
      attendance among the mentally ill population. An audit was conducted of a breast
      screening service in inner London to determine uptake rates in women with mental
      illness. DESIGN: Cross sectional data linkage study of the local screening
      register and patients of the local psychiatric units. Screening uptake rates in
      all patients, those with a history of multiple detention in hospital, and those
      with psychosis were compared with the local reference population. SETTING: Women
      in three inner London boroughs. PARTICIPANTS: Screening records for 933
      psychiatric patients and 44 195 women without mental health problems aged 50 to
      64 years. MAIN RESULTS: Overall, psychiatric patients were as likely as the
      reference group to attend breast screening. Patients with a history of multiple
      detention were significantly less likely to attend (OR = 0.40, 0.29 to 0.55;
      p<0.001), as were patients with a diagnosis of psychosis (OR = 0.33, 0.18 to
      0.61; p<0.01). Increasing age, a history of detention in hospital, and social
      deprivation remained independent predictors for non-attendance. CONCLUSION: Women
      with severe mental health problems may be less likely to attend national
      screening programmes such as breast screening, and action should be taken to
      overcome the barriers to attendance.

PMID- 16790833
TI  - Myocardial infarction symptom recognition by the lay public: the role of gender
      and ethnicity.
AB  - STUDY OBJECTIVE: To find out if gender and ethnicity are associated with acute
      myocardial infarction (AMI) symptom recognition and the recommendation of
      enlisting emergency medical services. DESIGN: In an experiment, a random sample
      of the public was provided a scenario of a person experiencing symptoms of AMI;
      the gender of the character (male, female, or indeterminate) was manipulated.
      SETTING: Vancouver, Canada PARTICIPANTS: 976 people from a population based
      random sample of 3419 people, 40 years of age and older, participated in a
      telephone survey given in English, Cantonese, Mandarin, and Punjabi. MAIN
      RESULTS: 78% of the respondents identified the symptoms as heart related.
      Unadjusted analyses showed that ethnicity, education, income, and AMI knowledge
      were significantly associated with symptom recognition (Chinese respondents were
      least likely to identify the symptoms as heart related). Thirty seven per cent
      recommended calling emergency services, which was associated with symptom
      recognition, ethnicity (Chinese respondents were least likely to make the
      recommendation), AMI knowledge, having an immediate family member with AMI, and
      having talked with a health professional about the signs and symptoms of AMI.
      Neither the gender of the respondent nor of the affected person in the scenario
      was associated with symptom recognition. CONCLUSIONS: Heart health education must
      be targeted to and tailored for ethnic communities. Health professionals must
      discuss the signs and symptoms of AMI, and the correct course of action, with
      their patients.

PMID- 16790834
TI  - Parental share in public and domestic spheres: a population study on gender
      equality, death, and sickness.
AB  - STUDY OBJECTIVE: Examine the relation between aspects of gender equality and
      population health based on the premise that sex differences in health are mainly
      caused by the gender system. SETTING/ PARTICIPANTS: All Swedish couples (98 240
      people) who had their first child together in 1978. DESIGN: The exposure of
      gender equality is shown by the parents' division of income and occupational
      position (public sphere), and parental leave and temporary child care (domestic
      sphere). People were classified by these indicators during 1978-1980 into
      different categories; those on an equal footing with their partner and those who
      were traditionally or untraditionally unequal. Health is measured by the outcomes
      of death during 1981-2001 and sickness absence during 1986-2000. Data are
      obtained by linking individual information from various national sources. The
      statistical method used is multiple logistic regressions with odds ratios as
      estimates of relative risks. MAIN RESULTS: From the public sphere is shown that
      traditionally unequal women have decreased health risks compared with equal
      women, while traditionally unequal men tend to have increased health risks
      compared with equal men. From the domestic sphere is indicated that both women
      and men run higher risks of death and sickness when being traditionally unequal
      compared with equal. CONCLUSIONS: Understanding the relation between gender
      equality and health, which was found to depend on sex, life sphere, and
      inequality type, seems to require a combination of the hypotheses of convergence,
      stress and expansion.

PMID- 16790835
TI  - Breast feeding and blood lipid concentrations in male Brazilian adolescents.
AB  - OBJECTIVE: To assess the association between breast feeding and blood lipid
      levels in adolescence. DESIGN: Population based prospective birth cohort study.
      SETTING: City of Pelotas, Brazil. SUBJECTS: All hospital births taking place in
      1982; 79% of all males (n = 2250) were followed up for 18 years, and 2089 blood
      samples were available. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Total
      cholesterol and fractions (very low density lipoprotein cholesterol (VLDL), low
      density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol
      (HDL)), LDL/HDL ratio, serum triglycerides. RESULTS: Three breast feeding
      variables were studied: total duration of breast feeding, duration of exclusive
      or predominant breast feeding, and ever compared with never breast fed. Adjusted
      analyses were controlled for family income, household assets index, maternal
      education, maternal pre-pregnancy body mass index (BMI), skin colour, birth
      weight, gestational age, maternal smoking during pregnancy, and adolescent BMI,
      and behavioural variables (fat content of diet, physical activity, smoking, and
      alcohol drinking). Only one association reached borderline significance (p =
      0.05): LDL cholesterol was slightly higher among never (mean 41.0 mg/dl; 95% CI
      39.4 to 42.7) than among ever breast fed men (38.6 mg/dl; 95% CI 38.6 to 40.3),
      in the adjusted analyses. All other associations were not significant (p> or
      =0.09). There was no evidence of effect modification according to preterm status,
      intrauterine growth retardation, socioeconomic level, growth velocity in the
      first two years of life, or nutritional status at 2 years of age. CONCLUSIONS:
      There was no clear association between breast feeding duration and serum lipid
      concentrations at the age of 18 years in this sample of Brazilian men.

PMID- 16790836
TI  - Physical activity among elderly people in a city population: the influence of
      neighbourhood level violence and self perceived safety.
AB  - STUDY OBJECTIVE: To study the associations between neighbourhood level
      violence/fear of violence and physical activity among elderly people, accounting
      for somatic health. DESIGN: Self reported data from the Oslo health study, a
      cross sectional study conducted in 2000, were linked with sociodemographic and
      social security data from Statistics Norway. A multilevel regression analysis was
      conducted by MlwiN using contextual level variables provided by the Oslo City
      Council. SETTING: Oslo, Norway. PARTICIPANTS: 3499 inhabitants aged 74/5 (53.2%
      of all invitees). MAIN RESULTS: 20.5% of the elderly were physically active less
      than one hour a week. Somatic health was clearly associated with physical
      activity among both men and women. Neighbourhood level violence was associated
      with physical activity only for men, while fear of violence was only associated
      with physical activity for women. Differences in somatic health did not explain
      differences in physical activity between neighbourhoods. These differences were
      explained by socioeconomic variables, and neighbourhood level violence/fear of
      violence. CONCLUSIONS: In a sample of presumably healthy 75/76 year olds in Oslo,
      the associations between neighbourhood level violence and physical activity
      (among men), and fear of violence and physical activity (among women), are of the
      same sizes as those between somatic health and physical activity. These two
      dimensions of violence have, in contrast with somatic health, an explanatory
      function in exploring differences in physical activity between neighbourhoods in
      Oslo.

PMID- 16790837
TI  - Do biomarkers of stress mediate the relation between socioeconomic status and
      health?
AB  - OBJECTIVES: To test the relation between socioeconomic status (SES) and
      biomarkers of chronic stress, including basal cortisol, and to test whether these
      biomarkers account for the relation between SES and health outcomes. DESIGN:
      Cross sectional study using data from the 2000 social and environmental
      biomarkers of aging study (SEBAS). SETTING: Taiwan. PARTICIPANTS: Nationally
      representative sample of 972 men and women aged 54 and older. MAIN OUTCOME
      MEASURES: Highest risk quartiles for 13 biomarkers representing functioning of
      the neuroendocrine system, immune/inflammatory systems, and the cardiovascular
      system: cortisol, adrenaline (epinephrine), noradrenaline (norepinephrine), serum
      dihydroepiandrosterone sulphate (DHEA-S), insulin-like growth factor 1 (IGF1),
      interleukin 6 (IL6), albumin, systolic blood pressure, diastolic blood pressure,
      waist-hip ratio, total cholesterol-HDL ratio, HDL cholesterol, and glycosylated
      haemoglobin; self reported health status (1-5) and self reported mobility
      difficulties (0-6). RESULTS: Lower SES men have greater odds of falling into the
      highest risk quartile for only 2 of 13 biomarkers, and show a lower risk for 3 of
      the 13 biomarkers, with no association between SES and cortisol. Lower SES women
      have a higher risk for many of the cardiovascular risk factors, but a lower risk
      for increased basal readings of adrenaline, noradrenaline, and cortisol.
      Inclusion of all 13 biological markers does not explain the relation between SES
      and health outcomes in the sample. CONCLUSIONS: These data do not support the
      hypothesis that chronic stress, via sustained activation of stress related
      autonomic and neuroendocrine responses, is an important mediator in the relation
      between SES and health outcomes. Most notably, lower SES is not associated with
      higher basal levels of cortisol in either men or women. These results place an
      increased burden of proof on researchers who assert that psychosocial stress is
      an important pathway linking SES and health.

PMID- 16790838
TI  - Transmission potential of primary pneumonic plague: time inhomogeneous evaluation
      based on historical documents of the transmission network.
AB  - BACKGROUND: The transmission potential of primary pneumonic plague, caused by
      Yersinia pestis, is one of the key epidemiological determinants of a potential
      biological weapon, and requires clarification and time dependent interpretation.
      METHOD: This study estimated the reproduction number and its time dependent
      change through investigations of outbreaks in Mukden, China (1946), and
      Madagascar (1957). Reconstruction of an epidemic tree, which shows who infected
      whom, from the observed dates of onset was performed using the serial interval.
      Furthermore, a likelihood based approach was used for the time inhomogeneous
      evaluation of the outbreaks for which there was scarcity of cases. RESULTS:
      According to the estimates, the basic reproduction number, R(0), was on the order
      of 2.8 to 3.5, which is higher than previous estimates. The lower 95% confidence
      intervals of R(0) exceeded unity. The effective reproduction number declined
      below unity after control measures were introduced in Mukden, and before the
      official implementation in Madagascar. CONCLUSION: While the time course of the
      latter outbreak could be explained by intrinsic factors and stochasticity in this
      remote and scarcely populated area, the former in Mukden suggests the possible
      continued chains of transmission in highly populated areas. Using the proposed
      methods, the who infected whom information permitted the evaluation of the time
      inhomogeneous transmission potential in relation to public health measures. The
      study also tackles the problem of statistical estimation of R(0) based on similar
      information, which was previously performed simply by counting the number of
      secondary transmissions regardless of time.

PMID- 16790839
TI  - Income inequality and the prevalence of mental illness: a preliminary
      international analysis.

PMID- 16790840
TI  - Regulation of hepatic fatty acid elongase and desaturase expression in diabetes
      and obesity.
AB  - Fatty acid elongases and desaturases play an important role in hepatic and whole
      body lipid composition. We examined the role that key transcription factors
      played in the control of hepatic elongase and desaturase expression. Studies with
      peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice
      establish that PPARalpha was required for WY14643-mediated induction of fatty
      acid elongase-5 (Elovl-5), Elovl-6, and all three desaturases [Delta(5)
      desaturase (Delta(5)D), Delta(6)D, and Delta(9)D]. Increased nuclear sterol
      regulatory element binding protein-1 (SREBP-1) correlated with enhanced
      expression of Elovl-6, Delta(5)D, Delta(6)D, and Delta(9)D. Only Delta(9)D was
      also regulated independently by liver X receptor (LXR) agonist. Glucose induction
      of l-type pyruvate kinase, Delta(9)D, and Elovl-6 expression required the
      carbohydrate-regulatory element binding protein/MAX-like factor X (ChREBP/MLX)
      heterodimer. Suppression of Elovl-6 and Delta(9)D expression in livers of
      streptozotocin-induced diabetic rats and high fat-fed glucose-intolerant mice
      correlated with low levels of nuclear SREBP-1. In leptin-deficient obese mice
      (Lep(ob/ob)), increased SREBP-1 and MLX nuclear content correlated with the
      induction of Elovl-5, Elovl-6, and Delta(9)D expression and the massive
      accumulation of monounsaturated fatty acids (18:1,n-7 and 18:1,n-9) in neutral
      lipids. Diabetes- and obesity-induced changes in hepatic lipid composition
      correlated with changes in elongase and desaturase expression. In conclusion,
      these studies establish a role for PPARalpha, LXR, SREBP-1, ChREBP, and MLX in
      the control of hepatic fatty acid elongase and desaturase expression and lipid
      composition.

PMID- 16790841
TI  - Prediction of RNA binding sites in proteins from amino acid sequence.
AB  - RNA-protein interactions are vitally important in a wide range of biological
      processes, including regulation of gene expression, protein synthesis, and
      replication and assembly of many viruses. We have developed a computational tool
      for predicting which amino acids of an RNA binding protein participate in RNA
      protein interactions, using only the protein sequence as input. RNABindR was
      developed using machine learning on a validated nonredundant data set of
      interfaces from known RNA-protein complexes in the Protein Data Bank. It
      generates a classifier that captures primary sequence signals sufficient for
      predicting which amino acids in a given protein are located in the RNA-protein
      interface. In leave-one-out cross-validation experiments, RNABindR identifies
      interface residues with >85% overall accuracy. It can be calibrated by the user
      to obtain either high specificity or high sensitivity for interface residues.
      RNABindR, implementing a Naive Bayes classifier, performs as well as a more
      complex neural network classifier (to our knowledge, the only previously
      published sequence-based method for RNA binding site prediction) and offers the
      advantages of speed, simplicity and interpretability of results. RNABindR
      predictions on the human telomerase protein hTERT are in good agreement with
      experimental data. The availability of computational tools for predicting which
      residues in an RNA binding protein are likely to contact RNA should facilitate
      design of experiments to directly test RNA binding function and contribute to our
      understanding of the diversity, mechanisms, and regulation of RNA-protein
      complexes in biological systems. (RNABindR is available as a Web tool from
      http://bindr.gdcb.iastate.edu.).

PMID- 16790842
TI  - Identification, cloning, and functional analysis of the human U6 snRNA-specific
      terminal uridylyl transferase.
AB  - Mammalian cells contain a highly specific terminal uridylyl transferase (TUTase)
      that exclusively accepts U6 snRNA as substrate. This enzyme, termed U6-TUTase,
      was purified from HeLa cell extracts and analyzed by microsequencing. All
      sequenced peptides matched a unique human cDNA coding for a previously unknown
      protein. Domain structure analysis revealed that the U6-TUTase also belongs to
      the well-characterized poly(A) polymerase protein superfamily. However, by amino
      acid sequence as well as RNA-binding motifs, human U6-TUTase is highly divergent
      from both the poly(A) polymerases and from the TUTases identified within the
      editing complexes of trypanosomes. After cloning, the recombinant U6-TUTase was
      expressed in HeLa cells. Analysis of its catalytical activity confirmed the
      identity of the cloned protein as U6-TUTase, exhibiting the same exclusive
      substrate specificity for U6 snRNA as the endogenous enzyme. That unique
      selectivity even excluded as substrate U6atac RNA, the functional homolog of the
      minor spliceosome. Finally, RNAi knockdown experiments revealed that U6-TUTase is
      essential for cell proliferation. Surprisingly, large amounts of the recombinant
      enzyme were found to accumulate within nucleoli.

PMID- 16790843
TI  - The role of a metastable RNA secondary structure in hepatitis delta virus
      genotype III RNA editing.
AB  - RNA editing plays a critical role in the life cycle of hepatitis delta virus
      (HDV). The host editing enzyme ADAR1 recognizes specific RNA secondary structure
      features around the amber/W site in the HDV antigenome and deaminates the amber/W
      adenosine. A previous report suggested that a branched secondary structure is
      necessary for editing in HDV genotype III. This branched structure, which is
      distinct from the characteristic unbranched rod structure required for HDV
      replication, was only partially characterized, and knowledge concerning its
      formation and stability was limited. Here, we examine the secondary structures,
      conformational dynamics, and amber/W site editing of HDV genotype III RNA using a
      miniaturized HDV genotype III RNA in vitro. Computational analysis of this RNA
      using the MPGAfold algorithm indicated that the RNA has a tendency to form both
      metastable and stable unbranched secondary structures. Moreover, native
      polyacrylamide gel electrophoresis demonstrated that this RNA forms both branched
      and unbranched rod structures when transcribed in vitro. As predicted, the
      branched structure is a metastable structure that converts readily to the
      unbranched rod structure. Only branched RNA was edited at the amber/W site by
      ADAR1 in vitro. The structural heterogeneity of HDV genotype III RNA is
      significant because not only are both conformations of the RNA functionally
      important for viral replication, but the ratio of the two forms could modulate
      editing by determining the amount of substrate RNA available for modification.

PMID- 16790844
TI  - The fragile X mental retardation protein interacts with a distinct mRNA nuclear
      export factor NXF2.
AB  - Loss of fragile X mental retardation protein, FMRP, causes the fragile X
      syndrome. Highly expressed in the brain and testis, FMRP has been implicated in
      the transport and translation of specific mRNAs. Here we show that FMRP and the
      mRNA nuclear export factor NXF2 co-express in the mouse male germ cells and
      hippocampal neurons and that FMRP associates with NXF2 but not with its close
      relative NXF1. We thus hypothesize that FMRP and NXF2 may act in concert to
      promote the nucleocytoplasmic transport of specific mRNAs in male germ cells and
      neurons.

PMID- 16790845
TI  - Current status of renal transplantation.
AB  - Renal transplantation is the best treatment for most patients with end-stage
      renal failure. It markedly improves quality of life and in some cases increases
      life expectancy. Advances in immunosuppression and other areas of practice have
      led to an incremental improvement in outcome; 1- and 5-yr graft survival after
      cadaveric renal transplantation is now around 90 and 70%, respectively. This
      success has led to increased demand for transplantation that cannot be met by
      cadaveric heart-beating donors, numbers of which have remained relatively static.
      Increasing use is now being made of kidneys from so-called "marginal" or
      "extended criteria" cadaveric donors and from non-heart-beating donors. More
      reliance is also being placed on living kidney donation, which accounts for
      around 25% of kidney transplants in the United Kingdom and 50% of transplants in
      the United States. Much effort in renal transplantation is now being directed
      toward improving long-term outcomes. This chapter provides an overview of these
      and other issues in renal transplantation, focusing on some of the topics of
      current interest.

PMID- 16790846
TI  - Current status of liver transplantation.
AB  - Liver transplantation has become the treatment of choice for a wide range of end
      stage liver disease. As outcomes have improved, so the demand for this therapy
      has increasingly exceeded the availability of donor organs. Access to liver
      transplantation is controlled such that donor organs are generally allocated to
      the patients who are likely to benefit most, although if all patients who might
      benefit were placed on the waiting list, the donor shortage would be greatly
      increased. Recurrence of the original liver disease is emerging as an important
      issue. Fewer patients are transplanted for liver tumors, as earlier results
      showed a very high rate of recurrence. In recent years there has been a change in
      the underlying conditions of patients on the waiting list, and a preponderance of
      patients now present with hepatitis C and alcoholic cirrhosis. Increasingly,
      transplant units are looking to sources of donor organs that would previously
      have been deemed unsuitable--such marginal donors include non-heart-beating
      donors (NHBDs). Results from controlled NHBDs--those cases in which cardiac
      arrest is predicted--suggest that this is a good source of viable organs.
      Splitting a donor liver to provide two grafts has successfully enabled the
      transplantation of a child and an adult from one organ. The transplantation of
      two adults from a single organ remains a greater challenge. Transplantation from
      living donors has been practiced increasingly over the last decade, although
      anxieties have been expressed over donor safety. In many countries this now
      represents a significant contribution to overall liver transplant activity.

PMID- 16790847
TI  - Current status of clinical islet cell transplantation.
AB  - Clinical outcomes of pancreas transplantation were superior to that of islet
      transplantation until the introduction of the Edmonton protocol. Significant
      advances in islet isolation and purification technology, novel immunosuppression
      and tolerance strategies, and effective antiviral prophylaxis have renewed
      interest in clinical islet transplantation for the treatment of diabetes
      mellitus. The introduction of a steroid-free antirejection protocol and islets
      prepared from two donors led to high rates of insulin independence. The Edmonton
      protocol has been successfully replicated by other centers in an international
      multicenter trial. A number of key refinements in pancreas transportation, islet
      preparation, and newer immunological conditioning and induction therapies have
      led to continued advancement through extensive collaboration between key centers.
      This chapter provides an overview of the history of islet transplantation
      followed by a discussion of the state of the art of clinical islet
      transplantation. The challenges facing the clinician-scientist in the 21st
      century are also presented in this review.

PMID- 16790848
TI  - Current status of lung transplantation.
AB  - Lung transplantation has come of age with the development of a critical mass of
      experienced clinicians who are committed to pooling their knowledge to solve the
      clinical problems that continue to confound the benefits individual patients may
      enjoy from these life-saving procedures. Adequately powered clinical trials are
      in progress to assist decision making regarding the role of newer
      immunosuppressive agents. Therapeutic drug monitoring has become critical to
      minimizing preventable complications such as renal dysfunction with calcineurin
      inhibitors. Fibroproliferation inhibitors are used more widely to ameliorate the
      abnormal healing response to allodependent or alloindependent injury, the latter
      perhaps related to underrecognized gastroesophageal reflux disease for which
      fundoplication is now proposed as an effective preventative measure. Cumulative
      damage to the graft from low-grade rejection is now appreciated as a potential
      cause of graft loss perhaps via an insidious small vessel vasculitis causing
      bronchiolar ischemic injury. Clearly, despite some progress, substantive
      challenges remain.

PMID- 16790849
TI  - Chronic rejection in the heart.
AB  - The dramatic improvements in 1-yr survival following cardiac transplantation have
      not been matched by similar improvements in long-term graft survival. Long-term
      survival of allografted hearts is limited by a progressive fibroproliferative
      disease, resulting in intimal thickening and occlusion of the grafted coronary
      vessels. This disease, variously known as accelerated transplant coronary artery
      disease or cardiac graft vasculopathy, is also known as chronic rejection. The
      histology and clinical sequelae are briefly described. The disease can be thought
      of as a model for non-transplant atherosclerosis, postangioplasty restenosis, and
      vein graft atherosclerosis. There is compelling evidence that it is driven by
      alloantigen-dependent mechanisms. The evolution of the disease consists of three
      phases, an antibody-mediated phase, a cell-mediated phase, and a phase of tissue
      remodeling that is dependent on cytokines and growth factors. Experimental
      studies show that adoptive transfer of immunoglobulin can transfer features of
      intimal hyperplasia to transplanted arteries in immunodeficient recipients.
      Damage to donor endothelium is likely to be an important initiating factor in
      this disease because it exposes a thrombogenic subendothelial matrix. Whether T
      cells of antibody are most important in damaging the endothelium is currently the
      subject of much research. Although T cells are sometimes present in
      atherosclerotic lesions, an association with acute rejection has never been
      consistently shown.

PMID- 16790850
TI  - Direct and indirect allorecognition.
AB  - The design and effectiveness of strategies to promote long-term graft acceptance
      requires a fundamental understanding of the mechanisms underlying acute and
      chronic rejection. This chapter discusses the two pathways of allorecognition-
      direct and indirect--and suggests that the direct pathway plays a major role in
      the early weeks after transplantation and that the indirect pathway may
      contribute to the process of chronic rejection. The results of in vitro and in
      vivo experimental models are discussed, together with clinical data.

PMID- 16790851
TI  - HLA typing and its influence on organ transplantation.
AB  - Human leukocyte antigen (HLA) molecules are expressed on almost all nucleated
      cells, and they are the major molecules that initiate graft rejection. There are
      three classical loci at HLA class I: HLA-A, -B, and -Cw, and five loci at class
      II: HLA-DR, -DQ, -DP, -DM, and -DO. The system is highly polymorphic, there being
      many alleles at each individual locus. Three methods for HLA typing are described
      in this chapter, including serological methods and the molecular techniques of
      sequence-specific priming (SSP) and sequence-specific oligonucleotide probing
      (SSOP). The influence of HLA matching on solid organ and bone marrow
      transplantation is also described. HLA matching has had the greatest clinical
      impact in kidney and bone marrow transplantation, where efforts are made to match
      at the HLA-A, -B, and -DR loci. In heart and lung transplantation, although
      studies have shown it would be an advantage to match especially at the DR locus,
      practical considerations (ischemic times, availability of donors, clinical need
      of recipients) make this less of a consideration. Corneal grafts are not usually
      influenced by HLA matching, unless being transplanted into a vascularized (or
      inflamed) bed.

PMID- 16790852
TI  - Strategies for gene transfer to solid organs: viral vectors.
AB  - A major complication associated with transplantation of solid organs is
      immunological rejection, which is currently controlled pharmacologically with
      immunosuppressive drugs, which must be administered indefinitely and may have
      harmful side effects. Gene transfer to donor organs or recipient immune cells
      prior to transplantation could limit their use. The effects of transfer of
      candidate genes in experimental models of allograft rejection is outlined in this
      chapter, followed by a description of the features of an ideal gene-therapy
      vector. Finally, a brief overview of viral vector systems used commonly for gene
      transfer is presented.

PMID- 16790853
TI  - Nonviral vectors.
AB  - Gene therapy holds great promise for treating a variety of human diseases and
      conditions. The field of gene therapy has advanced rapidly in the last decade.
      However, a major limiting factor remains the lack of a suitable vector for gene
      delivery. Although viruses are currently the most commonly researched vector,
      because of continuing safety concerns research has broadened to developing
      nonviral alternatives. Nonviral vectors fall into several categories. They can be
      physical methods, which provide relatively crude delivery approaches, such as
      direct cell injection, or chemical delivery vehicles. Chemical vectors almost
      always include a polycation component to assist the passage of DNA to the cell's
      nucleus. The passage of the transgene through the cell to the nucleus is hampered
      by many obstacles. Approaches to overcome these, both intracellularly and
      extracellularly, in order to maximize gene expression are currently under
      investigation. Nonviral vectors offer a safe and versatile alternative to their
      viral counterparts. Although still in their infancy, the different nonviral
      approaches under development hold great potential for many clinical applications.

PMID- 16790854
TI  - Detection and clinical relevance of antibodies after transplantation.
AB  - Until recently, the role of antibodies in graft failure has been hampered by poor
      methods of defining specificity. Development of solid phase assays using purified
      major histocompatibility complex (MHC) molecules has greatly advanced our ability
      to monitor anti-human leukocyte antigen (HLA) antibodies in patients and to
      distinguish between HLA and non-HLA antibodies. The purpose of this chapter is to
      describe the methods for detecting antibodies and what we have learned in recent
      years regarding the role of well-defined antibodies to HLA and non-HLA antigens.
      Use of the complement-dependent lymphocytotoxic test was instrumental in defining
      patients who are sensitized to donor HLA antigens, and it still plays a major
      role in avoiding transplantation of organs into sensitized patients. However,
      solid phase assays are more useful for following patients posttransplant. A major
      advance has been the demonstration that anti-MHC class II antibodies are made
      late after transplantation and contribute to late graft failure. This has been
      demonstrated for renal and lung transplantation, but has not yet been confirmed
      for other organs. Clearer definition of non-HLA antibodies has been achieved,
      such as the autoantigen vimentin and MHC I-related chain A. Experimental studies
      using minor mismatched strain combinations confirm that non-HLA antibodies bind
      to donor endothelial cells; these antibodies seem to cause apoptosis but not
      complement-mediated lysis.

PMID- 16790855
TI  - Reprogramming the immune system using antibodies.
AB  - Tolerance induction induced by monoclonal antibodies or co-receptor blockade is
      robust enough to resist breakdown by adoptive transfer of lymphocytes. Such
      resistance, the hallmark of dominant tolerance, is mediated by CD4+ regulatory T
      cells. CD4+CD25+ T cells inhibit lymphopenia-mediated accumulation of T cells in
      vivo, but caution should be exerted when investigating antigen-specific
      regulation in replete mice. A number of different deletional and tolerogenic
      processes following antibody-induced tolerance are discussed in this chapter,
      including activation-induced cell death, immunosuppressive cytokines, and
      immunoprivileged sites. The possibility of spreading tolerance to other cells,
      including parenchymal cells, is also discussed. This chapter emphasizes recent
      evidence that shows that self-tolerance does not rely on several mechanisms
      running independently, but rather a continuum of synergistic and overlapping
      mechanisms.

PMID- 16790856
TI  - In vitro assays for immune monitoring in transplantation.
AB  - Because immune responses to transplant allografts are the main drivers of
      rejection, the ability to accurately quantitate antidonor immunity is an
      important goal in clinical transplantation. These allow for the prediction of
      presensitization to the transplanted tissue and the identification of rejection
      without needing more invasive tests. In this chapter, we will review three
      methods currently used in transplantation research. Limiting dilution assays are
      a traditional tool. The evolution of these assays has brought about the ELISpot.
      Developments in flow cytometry are also contributing to the understanding of the
      composition of the cells involved in these immune responses. We can therefore
      obtain a deeper understanding of the process of rejection and tolerance and their
      evolution with time. This chapter reviews in vitro assays in the context of
      transplantation, but the scientific applications of sensitive, accurate, and
      specific immune-monitoring reach well beyond this field of research.

PMID- 16790857
TI  - Proteomics and laser microdissection.
AB  - Two-dimensional gel electrophoresis (2-DE) combined with protein identification
      by mass spectrometry (MS) is currently the method of choice in the majority of
      proteomic projects. Novel gel-free technologies have been developed but 2-DE
      remains the technique of choice for quantitative expression profiling of large
      sets of complex protein mixtures such as whole cell/tissue lysates. Solubilized
      proteins are separated in the first dimension according to their charge
      properties (isoelectric point, pI) by isoelectric focusing (IEF) under denaturing
      conditions, followed by their separation in the second dimension by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), according to their
      relative molecular mass (Mr). 2-DE can resolve more than 5000 proteins
      simultaneously (approximately 2000 proteins routinely) and can detect less than 1
      ng of protein per spot. Furthermore, it delivers a map of intact proteins, which
      reflects changes in protein expression level, isoforms or posttranslational
      modifications. In this chapter we describe the various steps in the 2-DE
      proteomics workflow, namely sample preparation, solubilization, 2-D gel
      electrophoresis, protein detection and visualization, and protein identification
      by mass spectrometry. The use of 2-DE in conjunction with laser microdissection
      microscopy is presented and discussed.

PMID- 16790858
TI  - Real-time quantitative polymerase chain reaction in cardiac transplant research.
AB  - The real-time quantitative polymerase chain reaction (PCR), an increasingly
      popular technique for the detection of DNA, combines a high degree of accuracy
      with extreme sensitivity. In this chapter we describe the use of real-time
      quantitative PCR in transplantation research in two areas in which this method is
      commonly applied: the accurate quantification of mRNA in tissue samples and
      genotyping of DNA. These are described in the context of cardiac transplantation,
      but they are of equal relevance to other areas of transplant biology.

PMID- 16790859
TI  - Organ preservation.
AB  - The success of organ transplantation is critically dependent on the quality of
      the donor organ. Donor organ quality, in turn, is determined by a variety of
      factors including donor age and preexisting disease, the mechanism of brain
      death, donor management prior to organ procurement, the duration of hypothermic
      storage, and the circumstances of reperfusion. It has been recognized for some
      time that both the short- and long-term outcomes after cadaveric organ
      transplantation are significantly inferior to those obtained when the
      transplanted organ is obtained from a living donor, regardless of whether the
      donor is related or unrelated to the recipient. Brain death results in a series
      of hemodynamic, neurohormonal, and pro-inflammatory perturbations, all of which
      are thought to contribute to donor organ dysfunction. The process of
      transplantation exposes the donor organ to an obligatory period of ischemia and
      reperfusion. Traditionally, hypothermic storage of the donor organ has been used
      to protect it from ischemic injury, but donor organs differ markedly in their
      capacity to withstand hypothermic ischemia. Data from the Registry of the
      International Society for Heart and Lung Transplantation indicate that the risk
      of primary graft failure and death rises dramatically for both the heart and lung
      as ischemic time increases. Based on these data, maximum recommended ischemic
      times for the donor heart and lung are 6 and 8 h, respectively. In this chapter,
      strategies aimed at minimizing the adverse consequences of brain death and
      ischemia/reperfusion injury to the donor heart and lung are discussed. These
      strategies are likely to become increasingly important as the reliance on
      marginal donors increases to meet the growing demand for organ transplantation.

PMID- 16790860
TI  - Pharmacological manipulation of the rejection response.
AB  - Immunosuppressive strategies continue to evolve, with a number of new
      formulations having been developed in recent years. Although acute rejection
      rates may have diminished, current protocols of immunosuppression for chronic
      organ rejection are clearly inadequate. This complication remains the primary
      cause of graft loss months to years after solid organ transplant. In summary, the
      overall goal of achieving immune tolerance remains elusive. This chapter will
      focus on the pharmacological manipulation of the rejection response, reviewing
      historical and current recommended protocols. A brief outline of potential future
      pathways of targeted immunosuppression is described.

PMID- 16790861
TI  - Experimental models of graft arteriosclerosis.
AB  - Graft arteriosclerosis (GA) is the leading cause of mortality in long-term
      survivors of solid organ transplantation. Although clinical studies have
      suggested a multifactorial etiology, the precise mechanism of disease remains
      obscure. Many animal models have been developed that manifest lesions resembling
      those of human arteriosclerosis. These models have helped us address specific
      mechanistic and interventional issues but, for reasons that will be discussed,
      have failed to assign a unitary pathogenic mechanism to clinical GA. In this
      chapter we describe the commonly available experimental models of GA. We further
      discuss the merits and limitations of each model and outline their contribution
      to our understanding of the pathogenesis of the disease.

PMID- 16790862
TI  - Microchip capillary electrophoresis: an introduction.
AB  - Microchip capillary electrophoresis emerged in the early 1990s as an interesting
      and novel approach to the high-speed separation of biological compounds,
      including DNA and proteins. Since the early development in this area, growth in
      the research field has exploded and now includes chemists and engineers focused
      on developing new and better microchips, as well as biologists and biochemists
      who have begun to apply this exciting and still relatively new methodology to
      real-world problems. This chapter seeks to outline the historical development of
      microchip, the key elements of microchip capillary electrophoresis, and finally
      some of the important applications being developed that utilize microchip
      capillary electrophoresis.

PMID- 16790863
TI  - Fabrication of a glass capillary electrophoresis microchip with integrated
      electrodes.
AB  - In this chapter, a detailed outline delineating the processing steps for
      microfabricating capillary electrophoresis (CE) with integrated electrochemical
      detection (ECD) platforms for performing analyte separation and detection is
      presented to enable persons familiar with microfabrication to enter a cleanroom
      and fabricate a fully functional Lab-on-a-Chip (LOC) microdevice. The processing
      steps outlined are appropriate for the production of LOC prototypes using easily
      obtained glass substrates and common microfabrication techniques.
      Microfabrication provides a major advantage over existing macro-scale systems by
      enabling precise control over electrode placement, and integration of all
      required CE and ECD electrodes directly onto a single substrate with a small
      footprint. In the processing sequences presented, top and bottom glass substrates
      are photolithographically patterned and etched using wet chemical processing
      techniques. The bottom substrate contains seven electrodes required for CE/ECD
      operation, whereas the top substrate contains the microchannel network. The flush
      planar electrodes are created using sputter deposition and lift-off processing
      techniques. Finally, the two glass substrates are thermally bonded to create the
      final LOC device.

PMID- 16790864
TI  - Micro-molding for poly(dimethylsiloxane) microchips.
AB  - In the present chapter, some basic definitions about the photolithography process
      are explained and then the standard preparation of the silicon wafer, the
      fabrication of the mold, and the preparation and assembly of
      poly(dimethylsiloxane) (PDMS)-based microchips are discussed. The purpose of this
      chapter is to describe the most used techniques for preparation of PDMS
      microchips. A list of tips is included in order to provide a troubleshooting
      guide for the most common difficulties found during the fabrication process. Some
      recent alternative approaches to microfabrication are also discussed.

PMID- 16790865
TI  - Fabrication of polymer microfluidic systems by hot embossing and laser ablation.
AB  - Fabrication of microfluidic channels in common commercially available
      thermoplastic materials can be easily accomplished using hot embossing or
      ultraviolet (UV) laser ablation. Hot embossing involves replication of a
      microfluidic network in a polymer substrate from a stamp (or template) fabricated
      in silicon or metal. UV laser ablation is performed by either exposing the
      polymer substrate through a mask or by using a laser direct-write process. The
      resulting polymer microfluidic channels are most often sealed with another
      polymer piece using thermal bonding or solvent bonding to complete the
      fabrication procedure. Unlike their silicon and glass counterparts, polymer
      microfluidic systems can be fabricated by these methods in less than 1 h, making
      the materials attractive for both research prototyping and commercialization.

PMID- 16790866
TI  - Surface modification methods for enhanced device efficacy and function.
AB  - Currently available microfluidic devices can accomplish a variety of tasks useful
      in molecular biology. When moving analytical processes to a microenvironment, the
      properties of the device surface play a larger role in the functioning of the
      device. Surface modification may become necessary or advantageous for the purpose
      of control of the functional mechanics of the device, keeping cell components
      from adsorbing, attaching antibodies to the surface for detection of biological
      components, and attaching a functional bonding complex. Modification of the
      surface of microfluidic devices for the control of flow and device function, or
      for functionalization of the surface to tailor the device to a specific use, can
      be accomplished in numerous bench-top, postfabrication procedures. The use of
      polyelectrolyte multilayers, ultraviolet grafting of polymers, and
      polydimethylsiloxane/surfactant coating to control flow and mitigate adsorption
      is discussed. In addition, the functionalization of devices through amine
      termination of surfaces, and immobilization of biotin within a
      phosphotidylcholine bilayer is detailed.

PMID- 16790867
TI  - Polyelectrolyte coatings for microchip capillary electrophoresis.
AB  - In chip-based electrophoretic analysis of biomolecules, chemical modification of
      the microchannel is widely employed to reduce or eliminate the analyte-wall
      interactions and alter electroosmotic flow (EOF) in the microchannel. A stable
      polyelectrolyte multilayer coating is one common way to regulate or eliminate EOF
      and prevent analyte adsorption for the rapid, efficient separation of
      biomolecules within microchannels. A wide variety of polyelectrolytes have been
      used as coatings. This chapter deals with how to coat microchips with
      polyelectrolytes and the expected results using polybrene and dextran sulfate as
      models. The technique presented here is generally applicable to any
      polyelectrolyte.

PMID- 16790868
TI  - Interfacing microchip capillary electrophoresis with electrospray ionization mass
      spectrometry.
AB  - Microfluidic devices are a unique enabling technology for chemical separations,
      modification, and synthesis that are ideally suited for the manipulation of low
      volume samples on the order of a few nanoliters in volume. Complex patterns of
      capillary-sized channels with zero dead volume connections are the distinguishing
      features of many microfluidic devices. Concurrently, mass spectrometry has
      undergone further development, and is now arguably the method of choice for
      structural characterization of mass- and volume-limited samples. The production
      of ions in the gas phase from the solution phase is critical for direct coupling
      of fluidic devices with the mass spectrometer, and the electrospray ionization
      (ESI) sources are well suited for this application. Micro- and nanoflow ESI
      interfaces are ideal for these applications as they cover flow rate ranges from
      the hundreds to a few nanoliters per minute, which are the same as the flow rates
      used by most microfluidic devices. Herein, the assembly and operation of a simple
      ESI interface for coupling a microfluidic device and mass spectrometer is
      described.

PMID- 16790869
TI  - Interfacing amperometric detection with microchip capillary electrophoresis.
AB  - Amperometric detection is a sensitive and selective way to monitor separations in
      microchip capillary electrophoresis (CE). This review contains 78 references and
      will educate the reader of the issues that are involved with interfacing
      amperometric detection and microchip CE. These issues include special injection
      protocols, separation mechanisms, and ways to integrate the working electrode
      with the separation channel. Some useful biological applications of the technique
      will also be described.

PMID- 16790870
TI  - Conductivity detection on microchips.
AB  - Conductivity detection as a versatile detection technique for chip-based
      electrophoretic separation methods is described and the basic principles are
      discussed. The necessary electronic equipment and technologies to implement the
      detection electrodes on a microchip are presented. A difference between contact
      and contactless detection is made and the resulting advantages and problems are
      shown. Different analytical applications are listed and discussed that show the
      basic applicability of conductivity detection in capillary electrophoresis and in
      isotachophoresis, which may serve as a guideline for more specific developments
      in the future. Central to all applications is the choice of the buffer system. It
      determines not only the separation capability but also puts limits on the
      achievable dynamic detection range.

PMID- 16790871
TI  - DNA separations.
AB  - The use of two types of commercialized microfluidic chips for separation of
      double-stranded DNA (dsDNA), suitable for personal scale and high throughput use,
      is described. Compared with conventional approaches such as slab-gel and
      capillary electrophoresis (CE), these devices offer the advantages of faster
      separation times, better data reproducibility, greater ease of use, labor savings
      in quantitative analysis, and ease in data archiving and data sharing owing to
      the digital data format. With some simple precautions taken in keeping bubbles
      and particulates out of the microchannels, Lab-on-a-Chip devices have been
      adopted by many researchers in molecular biology and genomics laboratories to
      increase their productivity.

PMID- 16790872
TI  - Protein separations.
AB  - This chapter describes the use of two types of commercialized microfluidic chips
      for protein separation, suitable for personal scale and high-throughput use.
      Compared with conventional approaches, such as sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and capillary electrophoresis (CE),
      these devices offer the advantages of faster separation times, better data
      reproducibility, greater ease of use, labor savings in quantitative analysis, and
      ease in data archiving and data sharing owing to the digital data format. With
      some simple precautions taken to keep bubbles and particulates out of the
      microchannels, Lab-on-a-Chip devices have been adopted by many researchers in
      protein processing, protein engineering, and proteomics research laboratories to
      increase their productivity.

PMID- 16790873
TI  - Microchip capillary electrophoresis: application to peptide analysis.
AB  - The development of analytical methodologies to elucidate mechanisms of peptide
      transport and metabolism is important for the understanding of disease states and
      the design of effective drug therapies. Interest in the use of microchip
      capillary electrophoresis (CE) devices for peptide analysis stems from the
      ability to perform fast, highly efficient separations combined with small sample
      volume requirements. Many of the separation modes developed on conventional
      systems, including electrochromatography, isoelectric focusing, and
      electrophoretic bioaffinity assays, have been demonstrated on microchip devices.
      Steps that include sample preparation and labeling can also be integrated onto
      the microchip platform. This chapter will discuss considerations for peptide
      analysis using microchip CE and will focus on different approaches to sample
      preparation, separation, and detection.

PMID- 16790874
TI  - Measuring electroosmotic flow in microchips and capillaries.
AB  - Electrophoretic migration and electroosmotic flow (EOF) combine to determine the
      migration rate of charged compounds in capillary electrophoresis (CE) and
      microchip capillary electrophoresis (MCE). Uncontrolled and unmeasured changes in
      EOF will lead to irreproducible peak migration times and poor peak quantitation.
      The two most common methods for measuring EOF for CE and MCE are detailed.
      Experimental results for application of the neutral marker method and the current
      monitoring method to EC are presented, and related calculations of EOF rates and
      electroosmotic mobility are described. The strengths and shortcomings of these
      two EOF measurement techniques are discussed. Additional approaches for studying
      and measuring EOF and for improving the reproducibility of migration times for CE
      and MCE are summarized.

PMID- 16790875
TI  - Single cell analysis on microfluidic devices.
AB  - There is significant variability among cells of the same type at the single cell
      level. This variability may be because of external stimuli that vary temporally
      or spatially among a population of cells. It may also be owing to the
      nonsynchronized responses of cells to various stimuli. In addition, differences
      in otherwise similar cells may be generated by genetic mutations acquired by one
      or more of the cells. Often times multiple biochemical pathways and molecules are
      involved in such differences. In order to better understand these differences and
      to detect those rare cells in a large population that may be indicative of early
      disease states, methods that are capable of rapidly quantifying multiple
      molecular species in single cells are desired. Microfluidic devices may provide
      the optimal platform upon which to develop such methods. Microfluidics has the
      capability of combining the high-throughput manipulation and transport of cells
      with rapid, high-efficiency separations and high-sensitivity detection. This
      chapter describes how to fabricate microfluidic devices for the high-throughput
      manipulation and rapid electrical lysis of single, nonadherent (suspension) cells
      followed by the injection and separation of the fluorescently labeled cell
      contents.

PMID- 16790876
TI  - Rapid DNA amplification in glass microdevices.
AB  - The polymerase chain reaction (PCR) for amplification of DNA has become a very
      useful tool in scientific research and analytical laboratories, yet conventional
      techniques are time-consuming, and the reagents are expensive. Miniaturization of
      this technique has the potential to drastically reduce amplification time and
      reagent consumption while simultaneously improving the efficiency of the
      reaction. Increasing the surface area-to-volume ratio using microfluidic reaction
      chambers allows homogeneous solution temperatures to be achieved much more
      rapidly than in conventional heating blocks. Employing infrared radiation to
      selectively heat the reaction solution can additionally reduce the time and
      energy needed for thermocycling; the reaction container is not heated and can
      even serve as a heat sink for enhancement of cooling. Microchip systems also
      provide the potential for fabrication of structures for additional processing
      steps directly in line with the PCR chamber. Not only can amplification be
      integrated with product separation and analysis, but sample preparation steps can
      also be incorporated prior to amplification. The ultimate goal is a miniature
      total-analysis-system with seamlessly coupled sample-in/answer-out capabilities
      that consumes very low volumes of reagents and drastically reduces the time for
      analysis. This chapter will focus on the materials and methods involved in simple
      straight-channel microchip PCR on glass substrates using non-contact
      thermocycling.

PMID- 16790877
TI  - Outbreak of verotoxin producing E.coli O157 infections involving over forty
      schools in south Wales, September 2005.

PMID- 16790879
TI  - Tickborne encephalitis in Switzerland: significant increase in notified cases,
      2005.

PMID- 16790880
TI  - Avian influenza detected in Turkey and Romania.

PMID- 16790881
TI  - Cholera in Belgian tourists after travel to Turkey.

PMID- 16790883
TI  - Falciparum malaria acquired by a French tourist in a resort area of the Dominican
      Republic.

PMID- 16790882
TI  - Outbreak of trichinellosis due to consumption of bear meat from Canada, France,
      September 2005.

PMID- 16790885
TI  - Study of 1918 influenza pandemic virus provides information on origin and
      virulence mechanisms.

PMID- 16790886
TI  - H5N1 virus resistant to oseltamivir isolated from Vietnamese patient.

PMID- 16790887
TI  - Very low risk to human health from A/H5N1 avian influenza in Europe according to
      ECDC risk assessment.

PMID- 16790888
TI  - First isolation of Clostridium difficile PCR ribotype 027, toxinotype III in
      Belgium.

PMID- 16790889
TI  - Internationally adopted children as a source for MRSA.

PMID- 16790890
TI  - A case of Vibrio cholerae non-O1, non-O139 septicaemia in Slovenia, imported from
      Tunisia, July 2005.

PMID- 16790891
TI  - Outbreak of norovirus infections associated with consuming food from a catering
      company, Austria, September 2005.

PMID- 16790892
TI  - European Union bird importation bans in response to outbreaks of avian influenza
      in the region.

PMID- 16790893
TI  - Avian influenza outbreaks in the WHO European region and public health actions.

PMID- 16790894
TI  - Outbreak of Salmonella Goldcoast affecting tourists exposed in Majorca from the
      UK, Ireland, Sweden, Norway and Denmark.

PMID- 16790895
TI  - Cryptosporidiosis outbreak associated with eating in a canteen, Denmark, August
      2005.

PMID- 16790896
TI  - Outbreak of tuberculosis in a Stockholm nursery affects 35 children.

PMID- 16790897
TI  - Geographic mapping method shows potential for mapping influenza activity in
      Europe.

PMID- 16790899
TI  - Positron emission tomography.
AB  - The developments in positron emission tomography (PET) are reviewed with an
      emphasis on instrumentation for clinical PET imaging. After a brief summary of
      positron imaging before the advent of computed tomography, various improvements
      are highlighted including the move from PET scanners with septa to fully 3D
      scanners, changes in the preferred scintillators, efforts to improve the energy
      discrimination, and improvements in attenuation correction. Time-of-flight PET
      imaging is given special attention due to the recent revival of this technique,
      which promises significant improvement. Besides technical instrumentation
      efforts, other factors which influenced the acceptance of clinical PET are also
      discussed.

PMID- 16790900
TI  - Image reconstruction.
AB  - We give an overview of the role of Physics in Medicine and Biology in the
      development of tomographic reconstruction algorithms. We focus on imaging
      modalities involving ionizing radiation, CT, PET and SPECT, and cover a wide
      spectrum of reconstruction problems, starting with classical 2D tomography in the
      1970s up to 4D and 5D problems involving dynamic imaging of moving organs.

PMID- 16790901
TI  - The development of mammography.
AB  - This review traces the development of mammography physics over the last 50 years,
      concentrating mainly on technological changes and their inter-relations. It has
      been written for physicists with no specific mammography experience but a general
      interest in radiology, as much as for those with recent involvement in
      mammography. Topics covered include industrial film, xerography, intensifying
      screens, x-ray tube developments, image quality test objects, patient dose and
      performance checks. Some of these developments were necessary before population
      screening of healthy women could be considered, while others have resulted from
      increased opportunities for equipment manufactures which screening programmes
      created. The standpoint of this review is that of a physicist with long
      experience in a UK centre where mammography was performed on dedicated equipment
      well over 40 years ago and where screening has been performed continuously for 30
      years.

PMID- 16790902
TI  - Photon absorptiometry, bone densitometry and the challenge of osteoporosis.
AB  - During the lifetime of Physics in Medicine and Biology, osteoporosis has been
      recognized as the cause of a major health burden for societies, particularly
      within developed countries. The health detriment is associated with the
      consequences of bone fractures and the subsequent increases in morbidity and
      mortality. Much of the credit for the current availability of means for
      identifying groups of subjects at risk of fracture and the provision of means for
      the effective treatment of excessive bone loss can be attributed to the technique
      of dual photon absorptiometry. In this review, the history of the development of
      techniques based on the interactions of x- and gamma-rays with bone is considered
      and the ultimate dominance of x-ray based absorptiometry is described. The
      advantages and disadvantages of current absorptiometric techniques are presented
      and the likely future path for bone measurement is outlined.

PMID- 16790903
TI  - Nuclear medicine dosimetry.
AB  - A brief overview is provided of the history of the development of internal dose
      methods for use in nuclear medicine. Basic methods of internal dosimetry and the
      systems that have been developed for use in nuclear medicine are described. The
      development of the MIRD system and the International Radiopharmaceutical
      Dosimetry Symposium series is outlined. The evolution of models and tools for
      calculating dose estimates is reviewed. Current efforts in developing more
      patient-specific methods, particularly for use in therapy calculations,
      development of small scale and microdosimetry techniques, and of relating
      internal radiation doses to observed biological effects are described and
      evaluated.

PMID- 16790904
TI  - Development of methods for body composition studies.
AB  - This review is focused on experimental methods for determination of the
      composition of the human body, its organs and tissues. It summarizes the
      development and current status of fat determinations from body density, total
      body water determinations through the dilution technique, whole and partial body
      potassium measurements for body cell mass estimates, in vivo neutron activation
      analysis for body protein measurements, dual-energy absorptiometry (DEXA),
      computed tomography (CT) and magnetic resonance imaging (MRI, fMRI) and
      spectroscopy (MRS) for body composition studies on tissue and organ levels, as
      well as single- and multiple-frequency bioimpedance (BIA) and anthropometry as
      simple easily available methods. Methods for trace element analysis in vivo are
      also described. Using this wide range of measurement methods, together with
      gradually improved body composition models, it is now possible to quantify a
      number of body components and follow their changes in health and disease.

PMID- 16790905
TI  - The contribution of medical physics to the development of psoralen
      photochemotherapy (PUVA) in the UK: a personal reminiscence.
AB  - Psoralen photochemotherapy (PUVA) is the combined treatment of skin disorders
      with a photosensitizing drug (Psoralen) and UltraViolet A radiation. The
      introduction of PUVA therapy has arguably been the most important development in
      dermatology over the past 30 years and from the first days of the treatment being
      introduced in the UK, British medical physicists were an integral part of the
      effort to establish it. Medical physicists have contributed to this development
      in a number of ways, from designing irradiation units in the early days of the
      technique, through to collaborating with dermatologists in prosecuting clinical
      and experimental studies aimed at improving patient outcomes. That the dose of
      UVA radiation is administered quantitatively, and not qualitatively, has probably
      been the single most important contribution made by several medical physicists
      over this period. However, despite concerns that were expressed almost 30 years
      ago about the accuracy with which UVA doses are administered to patients, the
      medical physics community still has some way to go before we can be satisfied
      that statements about UVA irradiance and dose can be made with confidence.

PMID- 16790906
TI  - Review and history of photon cross section calculations.
AB  - Photon (x-ray, gamma-ray, bremsstrahlung) mass attenuation coefficients, mu/rho,
      are among the most widely used physical parameters employed in medical diagnostic
      and therapy computations, as well as in diverse applications in other fields such
      as nuclear power plant shielding, health physics and industrial irradiation and
      monitoring, and in x-ray crystallography. This review traces the evolution of
      this data base from its empirical beginnings totally derived from measurements
      beginning in 1907 by Barkla and Sadler and continuing up through the 1935 Allen
      compilation (published virtually unchanged in all editions up through 1971-1972
      of the Chemical Rubber Handbook), to the 1949 semi-empirical compilation of
      Victoreen, as our theoretical understanding of the constituent Compton
      scattering, photoabsorption and pair production interactions of photons with
      atoms became more quantitative. The 1950s saw the advent of completely
      theoretical (guided by available measured data) systematic compilations such as
      in the works of Davisson and Evans, and by White-Grodstein under the direction of
      Fano, using mostly theory developed in the 1930s (pre-World War II) by Sauter,
      Bethe, Heitler and others. Post-World War II new theoretical activity, and the
      introduction of the electronic automatic computer, led to the more extensive and
      more accurate compilations in the 1960s and 1970s by Storm and Israel, and by
      Berger and Hubbell. Today's mu/rho compilations by Cullen et al, by Seltzer,
      Berger and Hubbell, and by others, collectively spanning the ten decades of
      photon energy from 10 eV to 100 GeV, for all elements Z= 1 to 100, draw heavily
      on the 1970s shell-by-shell photoabsorption computations of Scofield, the 1960s
      coherent and incoherent scattering computations of Cromer et al, and the 1980
      computations of electron-positron pair and triplet computations of Hubbell, Gimm
      and Overbo, these names being representative of the vast legions of other
      researchers whose work fed into these computations.

PMID- 16790907
TI  - Development of radiobiology for oncology-a personal view.
AB  - When I came into radiotherapy in 1950, I was puzzled that some patients were
      treated to 3000 rads (cGy) in 3 weeks but others received 4000 in 5 or 6000 in 6
      weeks. When I asked why, there were no convincing answers given, except 'this is
      what we usually do'. It wasn't until I went to a course on 'Radiobiology for
      Radiotherapy' in Cambridge that I learnt about the basic theories of Douglas Lea
      and the very considerable history of research into radiobiology and clinical
      radiotherapy. And there were still some questions outstanding, such as the
      relative importance of intracellular repair between 'daily' fractions, whether a
      2 day gap each week was a good or a bad idea, and the role of proliferation, if
      any, during irradiation. I thought that a few simple animal experiments might
      help to give answers! That led me to a continuing interest in these questions and
      answers, which has taken me more than 50 years to pursue. This is the very
      personal story of what I saw happening in the subject, decade by decade. I was
      happy to experience all this together with scientists in many other countries,
      and our own, along the way.

PMID- 16790908
TI  - Fifty years of Monte Carlo simulations for medical physics.
AB  - Monte Carlo techniques have become ubiquitous in medical physics over the last 50
      years with a doubling of papers on the subject every 5 years between the first
      PMB paper in 1967 and 2000 when the numbers levelled off. While recognizing the
      many other roles that Monte Carlo techniques have played in medical physics, this
      review emphasizes techniques for electron-photon transport simulations. The broad
      range of codes available is mentioned but there is special emphasis on the
      EGS4/EGSnrc code system which the author has helped develop for 25 years. The
      importance of the 1987 Erice Summer School on Monte Carlo techniques is
      highlighted. As an illustrative example of the role Monte Carlo techniques have
      played, the history of the correction for wall attenuation and scatter in an ion
      chamber is presented as it demonstrates the interplay between a specific problem
      and the development of tools to solve the problem which in turn leads to
      applications in other areas.

PMID- 16790909
TI  - X-ray computed tomography.
AB  - X-ray computed tomography (CT), introduced into clinical practice in 1972, was
      the first of the modern slice-imaging modalities. To reconstruct images
      mathematically from measured data and to display and to archive them in digital
      form was a novelty then and is commonplace today. CT has shown a steady upward
      trend with respect to technology, performance and clinical use independent of
      predictions and expert assessments which forecast in the 1980s that it would be
      completely replaced by magnetic resonance imaging. CT not only survived but
      exhibited a true renaissance due to the introduction of spiral scanning which
      meant the transition from slice-by-slice imaging to true volume imaging.
      Complemented by the introduction of array detector technology in the 1990s, CT
      today allows imaging of whole organs or the whole body in 5 to 20 s with sub
      millimetre isotropic resolution. This review of CT will proceed in chronological
      order focussing on technology, image quality and clinical applications. In its
      final part it will also briefly allude to novel uses of CT such as dual-source
      CT, C-arm flat-panel-detector CT and micro-CT. At present CT possibly exhibits a
      higher innovation rate than ever before. In consequence the topical and most
      recent developments will receive the greatest attention.

PMID- 16790910
TI  - Brachytherapy technology and physics practice since 1950: a half-century of
      progress.
AB  - The 50-year tenure of Physics in Medicine and Biology has coincided with some of
      the most important developments in radiological science, including the
      introduction of artificial radioactivity, computers and 3D imaging into medicine.
      These events have profoundly influenced the development of brachytherapy.
      Although it is not the dominant radiotherapy modality, it continues to play an
      important role in cancer therapy, more than a century after its introduction.
      This paper reviews the impact of three broad categories of innovation introduced
      since 1950 from the North American perspective: the introduction of artificial
      radioactivity, computer- and image-based treatment planning, and basic single
      source dosimetry.

PMID- 16790911
TI  - Internal high linear energy transfer (LET) targeted radiotherapy for cancer.
AB  - High linear energy transfer (LET) radiation for internal targeted therapy has
      been a long time coming on to the medical therapy scene. While fundamental
      principles were established many decades ago, the clinical implementation has
      been slow. Localized neutron capture therapy, and more recently systemic targeted
      alpha therapy, are at the clinical trial stage. What are the attributes of these
      therapies that have led a band of scientists and clinicians to dedicate so much
      of their careers? High LET means high energy density, causing double strand
      breaks in DNA, and short-range radiation, sparing adjacent normal tissues. This
      targeted approach complements conventional radiotherapy and chemotherapy. Such
      therapies fail on several fronts. Foremost is the complete lack of progress for
      the control of primary GBM, the holy grail for cancer therapies. Next is the
      inability to regress metastatic cancer on a systemic basis. This has been the
      task of chemotherapy, but palliation is the major application. Finally, there is
      the inability to inhibit the development of lethal metastatic cancer after
      successful treatment of the primary cancer. This review charts, from an
      Australian perspective, the developing role of local and systemic high LET,
      internal radiation therapy.

PMID- 16790912
TI  - Back to the future: the history and development of the clinical linear
      accelerator.
AB  - The linear accelerator (linac) is the accepted workhorse in radiotherapy in 2006.
      The first medical linac treated its first patient, in London, in 1953, so the use
      of these machines in clinical practice has been almost co-existent with the
      lifetime of Physics in Medicine and Biology. This review is a personal selection
      of things the authors feel are interesting in the history, particularly the early
      history, and development of clinical linacs. A brief look into the future is also
      given. One significant theme throughout is the continuity of ideas, building on
      previous experience. We hope the review might re-connect younger radiotherapy
      physicists in particular with some of the history and emphasize the continual
      need, in any human activity, to remain aware of the past, in order to make best
      use of past experience when taking decisions in the present.

PMID- 16790913
TI  - IMRT: a review and preview.
AB  - The very first cornerstone paper on intensity-modulated radiation therapy (IMRT)
      was published in Physics in Medicine and Biology, and many seminal IMRT works
      have since appeared in this journal. Today IMRT is a widely used clinical
      treatment modality in many countries. This contribution to the 50th anniversary
      issue reviews the physical, mathematical, and technological milestones that have
      facilitated the clinical implementation and success of IMRT. In particular, the
      basic concepts and developments of both IMRT treatment planning ('inverse
      planning') and the delivery of cone-beam IMRT with a multileaf collimator from a
      fixed number of static beam directions are discussed. An outlook into the future
      of IMRT concludes the paper.

PMID- 16790914
TI  - The IMRT information process-mastering the degrees of freedom in external beam
      therapy.
AB  - The techniques and procedures for intensity-modulated radiation therapy (IMRT)
      are reviewed in the context of the information process central to treatment
      planning and delivery of IMRT. A presentation is given of the evolution of the
      information based radiotherapy workflow and dose delivery techniques, as well as
      the volume and planning concepts for relating the dose information to image based
      patient representations. The formulation of the dose shaping process as an
      optimization problem is described. The different steps in the calculation flow
      for determination of machine parameters for dose delivery are described starting
      from the formulation of optimization objectives over dose calculation to
      optimization procedures. Finally, the main elements of the quality assurance
      procedure necessary for implementing IMRT clinically are reviewed.

PMID- 16790915
TI  - Motion effects in (intensity modulated) radiation therapy: a review.
AB  - During a course of fractionated radiation therapy and between the fractions the
      tissues of the human body may move relative to some reference location in which
      the radiation therapy was planned. This has been known for over a century and
      simple 'coping mechanisms' (margins) have been used to approximately compensate.
      Since the introduction of highly accurate conformal radiation therapy and
      intensity-modulated radiation therapy (IMRT) attention has focused strongly in
      the last few years on understanding and compensating more appropriately for these
      motions. Thus, unlike most of the reviews in this special 50th anniversary issue
      which look back over decades of development, this one looks back at most within
      just the past decade and reviews the current situation. There is still much more
      work to be done and many of the techniques reviewed are themselves not yet
      implemented widely in the clinic.

PMID- 16790916
TI  - History of tomotherapy.
AB  - Tomotherapy is the delivery of intensity modulated radiation therapy using
      rotational delivery of a fan beam in the manner of a CT scanner. In helical
      tomotherapy the couch and gantry are in continuous motion akin to a helical CT
      scanner. Helical tomotherapy is inherently capable of acquiring CT images of the
      patient in treatment position and using this information for image guidance. This
      review documents technological advancements of the field concentrating on the
      conceptual beginnings through to its first clinical implementation. The history
      of helical tomotherapy is also a story of technology migration from academic
      research to a university-industrial partnership, and finally to commercialization
      and widespread clinical use.

PMID- 16790917
TI  - Magnetic resonance imaging-the Aberdeen perspective on developments in the early
      years.
AB  - From the beginnings of medical imaging with radioactivity, an account is given of
      the development in Aberdeen of CT scanners in nuclear medicine, and their
      clinical value, leading to the present-day gamma-cameras. Early animal work with
      electron magnetic resonance is described, which developed into a programme
      towards nuclear magnetic resonance of water in body tissues. The 1974 NMR image
      of a mouse, using the nuclear medicine experience, led to a quest to build the
      first clinically useful whole-body MRI. The work of other teams is outlined, and
      the steps which led to successful diagnostic images being made with the Aberdeen
      machine in 1980. The welcome from the medical fraternity, and the output of the
      multinational medical imaging companies, has led to the present-day, worldwide
      use of the MRI technique.

PMID- 16790918
TI  - Review of electron beam therapy physics.
AB  - For over 50 years, electron beams have been an important modality for providing
      an accurate dose of radiation to superficial cancers and disease and for limiting
      the dose to underlying normal tissues and structures. This review looks at many
      of the important contributions of physics and dosimetry to the development and
      utilization of electron beam therapy, including electron treatment machines, dose
      specification and calibration, dose measurement, electron transport calculations,
      treatment and treatment-planning tools, and clinical utilization, including
      special procedures. Also, future changes in the practice of electron therapy
      resulting from challenges to its utilization and from potential future technology
      are discussed.

PMID- 16790919
TI  - Proton therapy.
AB  - Proton therapy has become a subject of considerable interest in the radiation
      oncology community and it is expected that there will be a substantial growth in
      proton treatment facilities during the next decade. I was asked to write a
      historical review of proton therapy based on my personal experiences, which have
      all occurred in the United States, so therefore I have a somewhat parochial point
      of view. Space requirements did not permit me to mention all of the existing
      proton therapy facilities or the names of all of those who have contributed to
      proton therapy.

PMID- 16790920
TI  - Diagnostic imaging over the last 50 years: research and development in medical
      imaging science and technology.
AB  - Over the last 50 years, diagnostic imaging has grown from a state of infancy to a
      high level of maturity. Many new imaging modalities have been developed. However,
      modern medical imaging includes not only image production but also image
      processing, computer-aided diagnosis (CAD), image recording and storage, and
      image transmission, most of which are included in a picture archiving and
      communication system (PACS). The content of this paper includes a short review of
      research and development in medical imaging science and technology, which covers
      (a) diagnostic imaging in the 1950s, (b) the importance of image quality and
      diagnostic performance, (c) MTF, Wiener spectrum, NEQ and DQE, (d) ROC analysis,
      (e) analogue imaging systems, (f) digital imaging systems, (g) image processing,
      (h) computer-aided diagnosis, (i) PACS, (j) 3D imaging and (k) future directions.
      Although some of the modalities are already very sophisticated, further
      improvements will be made in image quality for MRI, ultrasound and molecular
      imaging. The infrastructure of PACS is likely to be improved further in terms of
      its reliability, speed and capacity. However, CAD is currently still in its
      infancy, and is likely to be a subject of research for a long time.

PMID- 16790921
TI  - Magnetic resonance spectroscopy (MRS) in the investigation of cancer at The Royal
      Marsden Hospital and The Institute of Cancer Research.
AB  - Developments in magnetic resonance spectroscopy (MRS) at The Royal Marsden
      Hospital and The Institute of Cancer Research are reviewed in the context of
      preceding developments in nuclear magnetic resonance (NMR) and MRS, and some of
      the early developments in this field, particularly those leading to human
      measurements. The early development of technology, and associated techniques for
      human measurement and assessment will be discussed, with particular reference to
      experience at out institutions. Applications using particular nuclei will then be
      described and related to other experimental work where appropriate. Contributions
      to the development of MRS that have been published in Physics in Medicine and
      Biology will be discussed.

PMID- 16790922
TI  - Ultrasound imaging.
AB  - Ultrasound imaging is now in very widespread clinical use. The most important
      underpinning technologies include transducers, beam forming, pulse compression,
      tissue harmonic imaging, contrast agents, techniques for measuring blood flow and
      tissue motion, and three-dimensional imaging. Specialized and emerging
      technologies include tissue characterization and image segmentation,
      microscanning and intravascular scanning, elasticity imaging, reflex transmission
      imaging, computed tomography, Doppler tomography, photoacoustics and
      thermoacoustics. Phantoms and quality assurance are necessary to maintain imaging
      performance. Contemporary ultrasonic imaging procedures seem to be safe but
      studies of bioeffects are continuing. It is concluded that advances in ultrasonic
      imaging have primarily been pushed by the application of physics and innovations
      in engineering, rather than being pulled by the identification of specific
      clinical objectives in need of scientific solutions. Moreover, the opportunities
      for innovation to continue into the future are both challenging and exciting.

PMID- 16790923
TI  - The early years of single photon emission computed tomography (SPECT): an
      anthology of selected reminiscences.
AB  - The origin of SPECT can be found in pioneering experiments on emission tomography
      performed approximately 50 years ago. This historical review consists of a
      compilation of first person recollections from nine trailblazing scientists who
      shaped the early years of SPECT instrumentation during the 1960s and 1970s.

PMID- 16790925
TI  - High-resolution structure of a plasmid-encoded dihydrofolate reductase:
      pentagonal network of water molecules in the D2-symmetric active site.
AB  - R67 plasmid-encoded dihydrofolate reductase (R67 DHFR) is an NADPH-dependent
      homotetrameric enzyme that catalyzes the reduction of dihydrofolate to
      tetrahydrofolate. The amino-acid sequence and molecular architecture of R67 DHFR
      and its inhibitory properties toward folate analogues are different from those of
      chromosomal DHFR. Here, the crystal structure of R67 DHFR refined using 1.1 A
      resolution data is presented. Blocked full-matrix least-squares refinement
      without restraints resulted in a final R factor of 11.4%. The anisotropic atomic
      displacement parameters analyzed by Rosenfield matrices and translation-libration
      screw validation suggested four quasi-rigid domains. A total of ten Calpha-H...O
      hydrogen bonds were identified between the beta-strands. There is reasonable
      structural evidence that His62 is not protonated in the tetramer, which is in
      accord with previous pH-profile studies. The side chain of Gln67 that protrudes
      into the active site exhibits dual conformation, a feature noticed for the first
      time owing to the availability of atomic resolution data. The R67 DHFR active
      site is unique: it has D2 symmetry and is a large active site with a pentagonal
      network of water molecules and exposure of backbone atoms to solvent; the central
      pore is favorable for planar ring-stacking interactions. The geometrical shape,
      overall symmetry, local asymmetry and waters appear to dominate the binding of
      ligands, catalysis and inhibition.

PMID- 16790924
TI  - Solution of protein crystallographic structures by high-pressure cryocooling and
      noble-gas phasing.
AB  - Room-pressure flash-cryocooling of protein crystals is the standard way to reduce
      radiation damage during data collection. Typically, it is necessary to find
      cryoprotection conditions by trial and error, a process that is not always
      successful. Recently, a new method, high-pressure cryocooling, was developed that
      does not require penetrative cryoprotectants and typically yields very high
      quality diffraction. Since this method involves helium gas as a pressurizing
      medium, it was of great interest to see whether the method could be extended to
      diffraction phasing by the incorporation of heavy noble gases such as krypton. A
      modified Kr-He high-pressure cyrocooling procedure is described wherein crystals
      are first pressurized with krypton gas to 10 MPa for 1 h. The krypton pressure is
      then released and the crystals are repressurized with helium over 150 MPa and
      cooled to liquid-nitrogen temperatures. Porcine pancreas elastase (PPE; 240
      residues, 26 kDa) was selected as a test case for this study. Excellent
      diffraction was achieved by high-pressure cryocooling without penetrating
      cryoprotectants. A single 0.31 occupied krypton site in a PPE molecule [Bijvoet
      amplitude ratio (|DeltaF|/F) of 0.53%] was successfully used for SAD phasing at
      1.3 A. This method has the potential to greatly simplify obtaining protein
      structures.

PMID- 16790926
TI  - In-house sulfur SAD phasing: a case study of the effects of data quality and
      resolution cutoffs.
AB  - Single-wavelength anomalous diffraction (SAD) utilizing the weak signal of
      inherently present S atoms can be successfully used to solve macromolecular
      structures, although this is mostly performed with data from a synchrotron rather
      than a laboratory source. Using high redundancy, sufficiently accurate anomalous
      data may now often be collected in the laboratory using Cu Kalpha X-ray
      radiation. Systematic analyses of a laboratory-derived data set illuminate the
      effects of data quality, redundancy and resolution cutoffs on the ability to
      locate the S atoms and phase the structure of Ptr ToxA, a 13.2 kDa toxin secreted
      by the fungus Pyrenophora tritici-repentis. Three sulfurs contributed to the
      successful phasing of the structure and were located using the program SHELXD. It
      is observed that data quality improves with increasing redundancy, but after a
      certain point becomes worse owing to crystal decay, so that there is an optimal
      amount of data to include for the sulfur substructure solution. Further, the
      success rate in locating S atoms is dramatically improved at lower resolutions
      and in a manner similar to data quality, there exists an optimal resolution at
      which the likelihood of solving the substructure is maximized. Based on these
      observations, a strategy for SAD data collection and substructure solution is
      suggested.

PMID- 16790927
TI  - Suggestive evidence for the involvement of the second calcium and surface loop in
      interfacial binding: monoclinic and trigonal crystal structures of a quadruple
      mutant of phospholipase A2.
AB  - The crystal structures of the monoclinic and trigonal forms of the quadruple
      mutant K53,56,120,121M of recombinant bovine pancreatic phospholipase A2 (PLA2)
      have been solved and refined at 1.9 and 1.1 A resolution, respectively.
      Interestingly, the monoclinic form reveals the presence of the second calcium
      ion. Furthermore, the surface-loop residues are ordered and the conformation of
      residues 62-66 is similar to that observed in other structures containing the
      second calcium ion. On the other hand, in the trigonal form the surface loop is
      disordered and the second calcium is absent. Docking studies suggest that the
      second calcium and residues Lys62 and Asp66 from the surface loop could be
      involved in the interaction with the polar head group of the membrane
      phospholipid. It is hypothesized that the two structures of the quadruple mutant,
      monoclinic and trigonal, represent the conformations of PLA2 at the lipid
      interface and in solution, respectively. A docked structure with a phospholipid
      molecule and with a transition-state analogue bound, one at the active site
      coordinating to the catalytic calcium and the other at the second calcium site,
      but both at the i-face, is presented.

PMID- 16790928
TI  - The structure of human neuronal Rab6B in the active and inactive form.
AB  - The Rab small G-protein family plays important roles in eukaryotes as regulators
      of vesicle traffic. In Rab proteins, the hydrolysis of GTP to GDP is coupled with
      association with and dissociation from membranes. Conformational changes related
      to their different nucleotide states determine their effector specificity. The
      crystal structure of human neuronal Rab6B was solved in its 'inactive' (with
      bound MgGDP) and 'active' (MgGTPgammaS-bound) forms to 2.3 and 1.8 A,
      respectively. Both crystallized in space group P2(1)2(1)2(1), with similar unit
      cell parameters, allowing the comparison of both structures without packing
      artifacts. Conformational changes between the inactive GDP and active GTP-like
      state are observed mainly in the switch I and switch II regions, confirming their
      role as a molecular switch. Compared with other Rab proteins, additional changes
      are observed in the Rab6 subfamily-specific RabSF3 region that might contribute
      to the specificity of Rab6 for its different effector proteins.

PMID- 16790929
TI  - Determination of the crystal structure of EntA, a 2,3-dihydro-2,3
      dihydroxybenzoic acid dehydrogenase from Escherichia coli.
AB  - The Escherichia coli enterobactin synthetic cluster is composed of six proteins,
      EntA-EntF, that form the enterobactin molecule from three serine molecules and
      three molecules of 2,3-dihydroxybenzoic acid (DHB). EntC, EntB and EntA catalyze
      the three-step synthesis of DHB from chorismate. EntA is a member of the short
      chain oxidoreductase (SCOR) family of proteins and catalyzes the final step in
      DHB synthesis, the NAD+-dependent oxidation of 2,3-dihydro-2,3-dihydroxybenzoic
      acid to DHB. The structure of EntA has been determined by multi-wavelength
      anomalous dispersion methods. Here, the 2.0 A crystal structure of EntA in the
      unliganded form is presented. Analysis of the structure in light of recent
      structural and bioinformatic analysis of other members of the SCOR family
      provides insight into the residues involved in cofactor and substrate binding.

PMID- 16790930
TI  - Automated ligand placement and refinement with a combined force field and shape
      potential.
AB  - An automated computational procedure for fitting a ligand into its electron
      density with the use of the MMFF94 force field and a Gaussian shape description
      has been developed. It employs a series of adiabatic optimizations of gradually
      increasing shape potential. Starting from a set of energy-relaxed ligand
      conformations, the final results are structures realistically strained to fit the
      crystallographic data.

PMID- 16790931
TI  - Detecting and overcoming hemihedral twinning during the MIR structure
      determination of Rna1p.
AB  - The structure of Rna1p was originally solved to 2.7 A resolution by MIRAS from
      crystals with partial hemihedral twinning in space group I4(1) [Hillig et al.
      (1999), Mol. Cell, 3, 781-791] by finding a low-twinned native crystal (twin
      fraction alpha=0.06) and after twin correction of all data sets. Rna1p crystals
      have now been used to examine how far twinning and twin correction affect MIR
      phasing with a higher resolution but highly twinned native data set. Even high
      hemihedral twinning [alphanative=0.39, alphaderivative=0.24] would not have
      hindered heavy-atom site identification of strong derivatives using difference
      Patterson maps. However, a weaker derivative could have been missed and
      refinement would have stalled at high R values had twinning not been identified
      and accounted for. Twin correction improved both site identification,
      experimental phasing statistics and MIR map quality. Different strategies were
      tested for refinement against twinned data. Using uncorrected twinned data and
      TWIN-CNS, Rna1p has now been refined to 2.2 A resolution (final twinned R and
      Rfree were 0.165 and 0.218, respectively). The increased resolution enabled
      release of the NCS restraints and allowed new conclusions to be drawn on the
      flexibility of the two molecules in the asymmetric unit. In the case of Rna1p,
      twinned crystal growth was possible owing to the presence of a twofold NCS axis
      almost parallel to the twin operator.

PMID- 16790932
TI  - Effect of crystal freezing and small-molecule binding on internal cavity size in
      a large protein: X-ray and docking studies of lipoxygenase at ambient and low
      temperature at 2.0 A resolution.
AB  - Flash-freezing is a technique that is commonly used nowadays to collect
      diffraction data for X-ray structural analysis. It can affect both the crystal
      and molecular structure and the molecule's surface, as well as the internal
      cavities. X-ray structural data often serve as a template for the protein
      receptor in docking calculations. Thus, the size and shape of the binding site
      determines which small molecules could be found as potential ligands in silico,
      especially during high-throughput rigid docking. Data were analyzed for wild
      soybean lipoxygenase-3 (MW 97 kDa) at 293 and 93 K and compared with the results
      from studies of its molecular complexes with known inhibitors, structures
      published by others for a derivative of the same enzyme (98 K) or a topologically
      close isozyme lipoxygenase-1 (at ambient temperature and 100 K). Analysis of
      these data allows the following conclusions. (i) Very small changes in the
      relative orientation of the molecules in the crystal can cause major changes in
      the crystal reciprocal lattice. (ii) The volume of the internal cavities can
      ;shrink' by several percent upon freezing even when the unit-cell and the protein
      molecular volume show changes of only 1-2%. (iii) Using a receptor structure
      determined based on cryogenic data as a target for computational screening
      requires flexible docking to enable the expansion of the binding-site cavity and
      sampling of the alternative conformations of the crucial residues.

PMID- 16790933
TI  - Time-dependent atomic coordinates for the dissociation of carbon monoxide from
      myoglobin.
AB  - Picosecond time-resolved crystallography was used to follow the dissociation of
      carbon monoxide from the heme pocket of a mutant sperm whale myoglobin and the
      resultant conformational changes. Electron-density maps have previously been
      created at various time points and used to describe amino-acid side-chain and
      carbon monoxide movements. In this work, difference refinement was employed to
      generate atomic coordinates at each time point in order to create a more explicit
      quantitative representation of the photo-dissociation process. After photolysis
      the carbon monoxide moves to a docking site, causing rearrangements in the heme
      pocket residues, the coordinate changes of which can be plotted as a function of
      time. These include rotations of the heme-pocket phenylalanine concomitant with
      movement of the distal histidine toward the solvent, potentially allowing carbon
      monoxide movement in and out of the protein and proximal displacement of the heme
      iron. The degree of relaxation toward the intermediate and deoxy states was
      probed by analysis of the coordinate movements in the time-resolved models,
      revealing a non-linear progression toward the unbound state with coordinate
      movements that begin in the heme-pocket area and then propagate throughout the
      rest of the protein.

PMID- 16790934
TI  - Structure of an orthorhombic form of xylanase II from Trichoderma reesei and
      analysis of thermal displacement.
AB  - An orthorhombic crystal of xylanase II from Trichoderma reesei was grown in the
      presence of sodium iodide. Crystal structures at atomic resolution were
      determined at 100 and 293 K. Protein molecules were aligned along a
      crystallographic twofold screw axis, forming a helically extended polymer-like
      chain mediated by an iodide ion. The iodide ion connected main-chain peptide
      groups between two adjacent molecules by an N-H...I-...H-N hydrogen-bond bridge,
      thus contributing to regulation of the molecular arrangement and suppression of
      the rigid-body motion in the crystal with high diffraction quality. The structure
      at 293 K showed considerable thermal motion in the loop regions connecting the
      beta-strands that form the active-site cleft. TLS model analysis of the thermal
      motion and a comparison between this structure and that at 100 K suggest that the
      fluctuation of these loop regions is attributable to the hinge-like movement of
      the beta-strands.

PMID- 16790935
TI  - Structure of the C2A domain of rabphilin-3A.
AB  - Rabphilin-3A is a neuronal protein containing a C2-domain tandem. To date, only
      the structure of the C2B domain has been solved. The crystal structure of the
      Ca2+-free C2A domain has been solved by molecular replacement and refined to 1.92
      A resolution. It adopts the classical C2-domain fold consisting of an eight
      stranded antiparallel beta-sandwich with type I topology. In agreement with its
      Ca2+-dependent negatively charged membrane-binding properties, this C2 domain
      contains all the conserved acidic residues responsible for calcium binding.
      However, the replacement of a conserved aspartic acid residue by glutamic acid
      allows formation of an additional strong hydrogen bond, resulting in increased
      rigidity of calcium-binding loop 1. The electrostatic surface of the C2A domain
      consists of a large positively charged belt surrounded by two negatively charged
      patches located at both tips of the domain. In comparison, the structurally very
      similar C2A domain of synaptotagmin I has a highly acidic electrostatic surface,
      suggesting completely unrelated functions for these two C2A domains.

PMID- 16790936
TI  - Structure of human ferritin L chain.
AB  - Ferritin is the major iron-storage protein present in all cells. It generally
      contains 24 subunits, with different ratios of heavy chain (H) to light chain
      (L), in the shape of a hollow sphere hosting up to 4500 ferric Fe atoms inside. H
      rich ferritins catalyse the oxidation of iron(II), while L-rich ferritins promote
      the nucleation and storage of iron(III). Several X-ray structures have been
      determined, including those of L-chain ferritins from horse spleen (HoSF),
      recombinant L-chain ferritins from horse (HoLF), mouse (MoLF) and bullfrog (BfLF)
      as well as recombinant human H-chain ferritin (HuHF). Here, structures have been
      determined of two crystal forms of recombinant human L-chain ferritin (HuLF)
      obtained from native and perdeuterated proteins. The structures show a cluster of
      acidic residues at the ferrihydrite nucleation site and at the iron channel along
      the threefold axis. An ordered Cd2+ structure is observed within the iron
      channel, offering further insight into the route and mechanism of iron transport
      into the capsid. The loop between helices D and E, which is disordered in many
      other L-chain structures, is clearly visible in these two structures. The
      crystals generated from perdeuterated HuLF will be used for neutron diffraction
      studies.

PMID- 16790937
TI  - The 1.9 A resolution structure of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5
      phosphate reductoisomerase, a potential drug target.
AB  - 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzes the NADPH-dependent
      rearrangement and reduction of 1-deoxy-D-xylulose 5-phosphate to form 2-C-methyl
      D-erythritol 4-phosphate, as the second step of the deoxyxylulose 5
      phosphate/methylerythritol 4-phosphate pathway found in many bacteria and plants.
      The end product, isopentenyl diphosphate, is the precursor of various isoprenoids
      vital to all living organisms. The pathway is not found in humans; the mevalonate
      pathway is instead used for the formation of isopentenyl diphosphate. This
      difference, combined with its essentiality, makes the reductoisomerase an
      excellent drug target in a number of pathogenic organisms. The structure of 1
      deoxy-D-xylulose 5-phosphate reductoisomerase from Mycobacterium tuberculosis
      (Rv2870c) was solved by molecular replacement and refined to a resolution of 1.9
      A. The enzyme exhibited an estimated kcat of 5.3 s-1 and Km and kcat/Km values of
      7.2 microM and 7.4x10(5) M-1 s-1 for NADPH and 340 microM and 1.6x10(4) M-1 s-1
      for 1-deoxy-D-xylulose 5-phosphate. In the structure, a sulfate is bound at the
      expected site of the phosphate moiety of the sugar substrate. The M. tuberculosis
      enzyme displays a similar fold to the previously published structures from
      Escherichia coli and Zymomonas mobilis. Comparisons offer suggestions for the
      design of specific drugs. Furthermore, the new structure represents an
      intermediate conformation between the open apo form and the closed holo form
      observed previously, giving insights into the conformational changes associated
      with catalysis.

PMID- 16790938
TI  - Structure of Escherichia coli tryptophanase.
AB  - Pyridoxal 5'-phosphate (PLP) dependent tryptophanase has been isolated from
      Escherichia coli and its crystal structure has been determined. The structure
      shares the same fold with and has similar quaternary structure to Proteus
      vulgaris tryptophanase and tyrosine-phenol lyase, but is found in a closed
      conformation when compared with these two enzymes. The tryptophanase structure,
      solved in its apo form, does not have covalent PLP bound in the active site, but
      two sulfate ions. The sulfate ions occupy the phosphoryl-binding site of PLP and
      the binding site of the alpha-carboxyl of the natural substrate tryptophan. One
      of the sulfate ions makes extensive interactions with both the transferase and
      PLP-binding domains of the protein and appears to be responsible for holding the
      enzyme in its closed conformation. Based on the sulfate density and the structure
      of the P. vulgaris enzyme, PLP and the substrate tryptophan were modeled into the
      active site. The resulting model is consistent with the roles of Arg419 in
      orienting the substrate to PLP and acidifying the alpha-proton of the substrate
      for beta-elimination, Lys269 in the formation and decomposition of the PLP
      quinonoid intermediate, Arg230 in orienting the substrate-PLP intermediates in
      the optimal conformation for catalysis, and His463 and Tyr74 in determining
      substrate specificity and suggests that the closed conformation observed in the
      structure could be induced by substrate binding and that significant
      conformational changes occur during catalysis. A catalytic mechanism for
      tryptophanase is proposed. Since E. coli tryptophanase has resisted forming
      diffraction-quality crystals for many years, the molecular surface of
      tryptophanase has been analyzed in various crystal forms and it was rationalized
      that strong crystal contacts occur on the flat surface of the protein and that
      the size of crystal contact surface seems to correlate with the diffraction
      quality of the crystal.

PMID- 16790939
TI  - Structure of 8Salpha globulin, the major seed storage protein of mung bean.
AB  - The 8S globulins of mung bean [Vigna radiata (L.) Wilczek] are vicilin-type seed
      storage globulins which consist of three isoforms: 8Salpha, 8Salpha' and 8Sbeta.
      The three isoforms have high sequence identities with each other (around 90%).
      The structure of 8Salpha globulin has been determined for the first time by X-ray
      crystallographic analysis and refined at 2.65 A resolution with a final R factor
      of 19.6% for 10-2.65 A resolution data. The refined 8Salpha globulin structure
      consisted of 366 of the 423 amino-acid residues (one subunit of the biological
      trimer). With the exception of several disordered regions, the overall 8Salpha
      globulin structure closely resembled those of other seed storage 7S globulins.
      The 8Salpha globulin exhibited the highest degree of sequence identity (68%) and
      structural similarity (a root-mean-square deviation of 0.6 A) with soybean beta
      conglycinin beta (7S globulin). Their surface hydrophobicities are also similar
      to each other, although their solubilities differ under alkaline conditions at
      low ionic strength. This difference seems to be a consequence of charge-charge
      interactions and not hydrophobic interactions of the surfaces, based on a
      comparison of the electrostatic potentials of the molecular surfaces. The thermal
      stability of 8Salpha globulin is lower than that of soybean beta-conglycinin
      beta. This correlates with the cavity size derived from the crystal structure,
      although other structural features also have a small effect on the protein's
      thermal stability.

PMID- 16790940
TI  - Assessment of a preliminary solubility screen to improve crystallization trials:
      uncoupling crystal condition searches.
AB  - The utility of a preliminary solubility screen has been assessed on ten test
      proteins. It is proposed that maximizing the protein solubility prior to crystal
      setups is likely to improve crystal growth. In crystallization setups, drops of a
      protein solution are mixed with various crystallization solutions which are then
      allowed to equilibrate. The protein solutions usually contain a salt and buffer
      which are present as a constant in all crystal screens. The propensity for
      crystallization, driven by three components of sparse-matrix screens, the
      buffers, salts and precipitating agents, could potentially be masked by the
      components of the protein solution. Ten test proteins were dissolved in a
      standard buffer (100 mM NaCl, 50 mM Tris-HCl pH 7.5) and in customized optimal
      buffers determined to maximize solubility. The proteins were then subjected to
      the Index (Hampton Research) 96-well sparse-matrix crystal screen and to a
      precipitant/precipitant-additive screen described here. Five of the ten proteins
      studied showed twofold to fourfold increases in the saturation level from
      standard to optimal buffer, two showed slight improvement and three showed a
      slight decrease. Microcrystals were obtained for all proteins and optimal buffer
      increased the appearance of crystals for eight of the ten proteins.

PMID- 16790941
TI  - Is interferon-alpha and retinoic acid combination along with radiation superior
      to chemo-radiation in the treatment of advanced carcinoma of cervix?
AB  - Locally advanced cervical cancers comprise a large majority of the gynecologic
      cancers in India and other developing countries. Concurrent chemo-radiation has
      improved the survival of high risk stage I and stage II cervical cancers. There
      is no evidence that the same survival benefit has been achieved with chemo
      radiation in stage III and stage IV disease. Interferon-alpha and Retinoic acid
      have synergistic anti-proliferative activity. In combination with radiation, they
      substantially enhance the sensitivity of the squamous carcinoma cells to
      radiation. Based on these observations from the in vitro studies, a few clinical
      trials have evaluated the combination of interferon-alpha and Retinoic acid,
      concomitant with radiation, to treat cervical cancers. The results from these
      early trials were encouraging and the combination had minimal toxicities.
      However, till date, no phase III randomized controlled trial has been done to
      evaluate this therapeutic modality.

PMID- 16790942
TI  - Oral squamous cell carcinoma: etiology, pathogenesis and prognostic value of
      genomic alterations.
AB  - Tumours of the head and neck comprise an important group of neoplasia, the
      incidence of which is increasing in many parts of the world. This increase
      remains high, despite all the advances in modern medicine. This malignancy is
      more prevalent in the developing world and unfortunately, has not received
      satisfactory attention as the more prevalent cancers of the developed world, like
      lung, breast, or colon cancer. Recent advances in diagnosis and therapeutic
      techniques of these lesions have yielded novel molecular targets, uncovered
      signal pathway dominance and advanced early cancer detection. This review covers
      recent advances in our understanding of the etiology, molecular changes and the
      possible role that genomic and proteomic research might play in the diagnosis and
      effective cure of this modern-day scourge.

PMID- 16790943
TI  - Survival in small cell lung cancer in India: prognostic utility of clinical
      features, laboratory parameters and response to treatment.
AB  - BACKGROUND: Predictors of survival and response to treatment in patients with
      small cell lung cancer (SCLC) are ill-defined and unclear. In an attempt to
      assess the impact of common presenting symptoms and laboratory values on
      survival, we undertook this retrospective review of patients with SCLC. To our
      knowledge, there is no study on survival in SCLC patients from the Indian
      subcontinent. DESIGN: Retrospective Cohort study. MATERIALS AND METHODS: All
      newly diagnosed small cell lung cancer cases from December 2001 through December
      2004, were identified and clinical data on presenting symptoms and laboratory
      findings from their hospital records, noted. The influence of various
      pretreatment factors on survival was investigated using Kaplan-Meier plots and
      Cox multivariate regression model. RESULTS: 76 subjects were included (84% males,
      91% smokers). 57% patients had five or more symptoms at presentation. Cumulative
      symptom burden was strongly associated with survival (P =0.02). Survival was also
      significantly related with Karnofsky performance status (KPS) (P =0.04), disease
      extent (P =0.03) and symptomatic response to treatment (P< 0.001). Patients with
      higher hemoglobin (P =0.02), serum sodium (P =0.04) and serum globulin (P =0.02),
      survived significantly longer. By multivariate regression analysis, hemoglobin,
      KPS and brain metastases, were significant predictors of survival (P =0.01, P
      =0.02, P< 0.01 respectively). CONCLUSION: Cumulative symptom burden, KPS, disease
      extent and symptomatic assessment of improvement after treatment, are useful
      predictors of survival. This has important clinical implications, keeping in
      view, the infrastructure and cost involved in more objective tests like CT scan,
      for evaluation of disease extent and prognosis. These findings can provide a
      simple basis for predicting prognosis in small cell lung cancer, especially in
      developing countries like ours.

PMID- 16790944
TI  - Treatment evaluation, follow-up and familial screening of medullary thyroid
      carcinoma by highly specific calcitonin measurements.
AB  - BACKGROUND: Calcitonin is the most sensitive and specific marker for medullary
      thyroid carcinoma (MTC). AIMS: The aim of this study was to emphasize the role
      and the limits of plasma basal calcitonin (bCT) measurement in the management of
      Moroccan MTC patients and their relatives. SETTINGS AND DESIGN: This is a
      retrospective study on 6 MTC patients referred to our institute from January 1996
      to December 2004. MATERIALS AND METHODS: Serum bCT levels were measured in 36
      individuals comprising six known MTC cases, 18 relatives and 12 healthy
      volunteers, using two-sites immunoradiometric assay method. Five of MTC patients
      have been followed from 12 to 96 months after surgery. STATISTICAL ANALYSIS USED:
      Calculations were performed using SPSS 10.0 program. Data comparison was done by
      Student's t -test. RESULTS: The circulating preoperative bCT concentrations were
      elevated for all MTC patients (range, 44,8 -2055 pg/ml, normal <10). Recent
      postoperative bCT determinations varied from 24.4 to 1972 pg/ml in four patients.
      In one patient, the bCT value decreased to an undetectable level during a follow
      up of 12 months. The mean bCT level of relatives was 4.90 +/- 3.54 pg/ml; two
      patients had slightly elevated bCT. Five (42%) healthy volunteers had
      undetectable bCT levels and all had less than 10 pg/ml; the mean bCT value was
      3.06 +/- 2.51 pg/ml. CONCLUSIONS: Routine plasma bCT measurement still has an
      important place in the preoperative diagnosis and follow-up treatment of MTC.

PMID- 16790946
TI  - Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain
      palliation in skeletal metastases.
AB  - BACKGROUND: Systemic therapy with radionuclides may be used for the treatment of
      patients with painful skeletal metastases owing to its efficacy, low cost and low
      toxicity. Imported radionuclides for pain palliation, like Strontium-89 are
      expensive; particularly for developing countries. In the Indian scenario,
      Samarium-153 (Sm-153) is produced in our own reactors and as a result, it is
      readily available and economical. AIM: We undertook this study to determine the
      efficacy and toxicity of single-dose Sm-153 ethylenediamine tetramethylene
      phosphonate as a palliative treatment for painful skeletal metastases. MATERIALS
      AND METHODS: Eightysix patients with painful skeletal metastases from various
      primaries, were treated with Sm-153 EDTMP at a dose of 37 MBq/kg. The effects
      were evaluated according to change in visual analogue pain score, analgesic
      consumption, Karnofsky performance score, mobility score and blood count tests,
      conducted regularly for 16 weeks. STATISTICS: Repeated measures analysis.
      RESULTS: The overall response rates were 73%, while complete response was seen in
      12.4%. Reduction in analgesic consumption with improvement in Karnofsky
      performance score and mobility score, was seen in all responders. Response rates
      were 80.3 and 80.5% in breast and prostate cancer, respectively. One case, each
      of Wilms tumor, ovarian cancer, germ cell tumor testis, multiple myeloma,
      primitive neuroectodermal tumor and oesophageal cancer, did not respond to
      therapy. No serious side-effects were noted, except for fall in white blood cell,
      platelet and haemoglobin counts, which gradually returned to normal levels by six
      eight weeks. CONCLUSION: Sm-153 EDTMP provided effective palliation in 73%
      patients with painful bone metastases: the major toxicity was temporary
      myelosuppression.

PMID- 16790945
TI  - Endocrine cancer in Iran: based on cancer registry system.
AB  - BACKGROUND: A population-based registry of endocrine cancer cases in four Iranian
      provinces, was performed for the years 1996-2000. MATERIALS AND METHODS: Patients
      in each province were grouped according to age, gender and tumor specifics (site,
      morphology, behavior) and the data was coded according to the international
      classification of diseases for oncology. STATISTICAL ANALYSIS USED: Person-years
      of population at risk were calculated and the results were presented as incidence
      rates by sex, age, age specific rates and age standard rate (ASR) per 100,000
      person-years, using direct method of standardization to the world population.
      RESULTS: A total of 319 cases of primary endocrine cancer were found and
      registered, including 313 cases of thyroid carcinoma and 6 cases of adrenal
      cancer. The thyroid carcinoma group cases consisted of papillary (82.7%),
      follicular (8.6%), medullary (7.0%) and anaplastic (1.6%) carcinomas. The ASR for
      thyroid carcinoma was 1.289 (0.627 for men, 1.59 for women), with the highest
      incidence rate in Kerman (ASR 1.643) and the lowest incidence rate in Golestan
      (ASR 0.735). For the 6 cases of adrenal cancer, 4 were neuroblastoma and 2 were
      pheochromocytoma. CONCLUSIONS: Iran was considered as an endemic, iodine
      deficient area, until fairly recently. Iodinization of salt has been started
      about 12 years ago, in the nation. Considering the effect of improvement in the
      iodine intake in previously deficient communities, which is associated with an
      increase in the incidence of papillary carcinoma compared to other histologic
      types, the frequency and distribution of histologic types of thyroid carcinoma
      was closer to what can be seen in iodine-rich areas.

PMID- 16790947
TI  - Unusual metastasis in colorectal cancer.
AB  - Metastasis from colorectal carcinoma occurs by either lymphatic or hematogenous
      spread. The most common sites of colorectal metastasis are the liver and lung.
      Involvement of the skin, muscles and bones are quite rare. The prognosis in such
      patients is usually poor. Herewith, we are reporting a case of colonic carcinoma
      who had cutaneous metastasis, muscular involvement and diffuse skeletal
      metastasis. At the end, she had brain metastasis, but liver and lung involvement
      was not observed till the end.

PMID- 16790948
TI  - The prevalence of needle stick injuries in medical, dental, nursing and midwifery
      students at the university teaching hospitals of Shiraz, Iran.
AB  - BACKGROUND: Medical, dental, nursing and midwifery students are at high risk for
      occupational exposure to blood-borne pathogens (BBPs) via sharp injuries such as
      needle stick injuries (NSIs). AIMS: The aim of this study was to determine the
      frequency of NSIs and the knowledge, attitude and practices of these students
      regarding their prevention. SETTINGS AND DESIGN: The clinical students at Shiraz
      University of Medical Sciences, Iran, were eligible to participate in a survey
      conducted by a self-administered questionnaire in 2004, asking them about NSIs
      during their clinical training undergraduate years. MATERIALS AND METHODS: A
      cross-sectional study evaluated NSIs and practices regarding protective
      strategies against BBPs in medical, dental, nursing and midwifery students at
      Shiraz University, Iran, in 2004. These students completed a self-administered
      questionnaire. STATISTICAL ANALYSIS: The data were entered into a personal
      computer using Epi-Info (version 2000). Chi-square and Fisher's exact tests for
      categorical variables and student t-test for continuous variables were performed,
      where appropriate, using SPSS version 10. Alpha was set at the 5% level. RESULTS:
      The questionnaire was completed by 688 (53%) students. 71.1% (489/688) of the
      students had NSIs that most commonly (43.6%) occurred in patient rooms. 82%
      (401/489) of NSIs were not reported. 87.8% (604/688) of the students received
      information about standard isolation precautions and 86.2% of them had been
      vaccinated against hepatitis B. CONCLUSION: NSIs and non-reporting of NSIs were
      highly prevalent in these students. Education about the transmission of blood
      borne infections, standard precautions and increasing availability of protection
      strategies must be provided.

PMID- 16790949
TI  - The impact of primary postpartum hemorrhage in "near-miss" morbidity and
      mortality in a tertiary care hospital in North India.
AB  - AIM: To assess risk factors, mortality and "near-miss" morbidity in early PPH.
      SETTING AND DESIGN: Retrospective analysis of 178 women with early PPH (within 24
      h of delivery) over 4 consecutive years in a tertiary care hospital in North
      India. MATERIALS AND METHODS: All case sheets of patients identified by labor
      record registers as having early PPH were reviewed by the same person to identify
      the actual impact of condition. The data was analyzed by chi-square analysis.
      RESULT: Early PPH (loss of blood that caused significant alteration in maternal
      condition or blood loss 500 in vaginal deliveries or> 1000 cc in cesarean
      section) was recorded in 178; 90 delivered in hospital (Group-A) and 88 referred
      after delivery (Group-B) from various peripheral centers, i.e., maternity
      hospitals, nursing homes, district and community health centers. The maternal
      mortality ratio during this period was 1049/100,000 (139 deaths/13248 live
      births; direct maternal deaths = 94). Early PPH accounted for 11/94 direct
      maternal deaths (11.7%). Of these 11 deaths, 3 were in group A and 8 in group B.
      "Near-miss" morbidity was higher than mortality (Total 19/178; 5/90 in Group-A
      and 14/88 in Group-B). Delayed referral and lack of active 3rd stage management
      in Group-B were responsible for most of the adverse events. CONCLUSION: Both
      "near-miss" morbidity and mortality in early PPH reflect the level of obstetric
      care in the developing world. These need to be reduced by strengthening
      peripheral delivery facilities, active 3rd stage management and early referral.

PMID- 16790950
TI  - Cerebrovascular manifestations in scorpion sting: a case series.
AB  - Cerebrovascular manifestations are uncommon presentations of scorpion sting in
      the Indian subcontinent. A prospective study was carried out on 50 patients with
      scorpion sting referred to the Government General Hospital during the period from
      April 2004 to March 2005. In all the patients, detailed history, physical
      examination with a specific neurological examination and routine biochemical
      testing and fundus examination were done. Computerized Tomography (CT) and
      Magnetic Resonance Imaging (MRI) were done in cases with neurological deficit.
      All these patients also underwent a complete hematological, rheumatologic and
      cardiovascular work-up for stroke. Cerebrovascular involvement was noted in four
      patients (8%). Hemorrhagic stroke was noted in two patients (4%) and thrombotic
      stroke was noted in two patients (4%). The mean time of presentation of
      neurological symptoms was 2 days. Stroke has been a common presentation in our
      series (8%). Contrary to world literature, there have been no reports of cranial
      nerve palsies or neuromuscular involvement in our series.

PMID- 16790951
TI  - Prophylactic antibiotic therapy in gynecologic-obstetric procedures: experience
      from three Iranian teaching hospitals.

PMID- 16790953
TI  - References: Far from uniformity.

PMID- 16790952
TI  - Clinical importance of solitary thyroid nodule of the thyroid in endemic goiter
      region.

PMID- 16790954
TI  - [Problems and possibility of resin abutment construction with a combined use of
      fiber posts: at the beginning of discussion].
AB  - When using post materials that are more rigid than teeth for abutment
      construction, tooth root fracture may be caused by stress concentration in the
      remaining part of the tooth root. Most of the tooth root fractures clinically
      observed in metal post abutment cases are longitudinal fractures, resulting in
      tooth extraction in many cases. In cases with sufficient coronal tooth substance,
      post-less abutment construction has recently been considered. Fiber posts have
      recently attracted attention as a post material for resin abutment construction
      due to their flexibility with elastic modulus similar to that of dentine. In
      Japan, although approval by the Ministry of Health, Labour and Welfare has
      recently been obtained, there have been few experimental studies and clinical
      reports on fiber posts. In this study, we performed a break-down test and finite
      element analysis of fiber posts as in vitro studies, and reviewed overseas
      references on clinical results. Experimental results show that, the effects on
      preventing stress concentration are high in all abutment construction methods
      when sufficient ferrule in the remaining teeth is present, and stress may be
      concentrated in the cervical area in fiber post abutment cases. Clinical results
      obtained from references showed that, fiber posts are superior to cast posts and
      commercially available metal posts, in terms of fracture and dislodgment.
      However, since issues were revealed in previous clinical studies, further
      comparison studies are necessary to evaluate the superiority of fiber posts
      compared with metal posts.

PMID- 16790955
TI  - [Skills Improvement Seminar for Submitting Articles to the Prosthodontic Research
      & Practice Journal. Part I. Guidelines for manuscript submission].
AB  - In the scientific meetings of the Japan Prosthodontic Society, many high-level
      research presentations are given, and yet a large proportion of the presentations
      have not been published. Since 2002, the Japan Prosthodontic Society has
      published PRP (Prosthodontic Research & Practice), which is the official English
      journal of the Society, to introduce scientific data of research in the field of
      prosthodontics internationally. PRP will be published quarterly from 2006. The
      editorial committee of the Japan Prosthodontic Society tries to give advice to
      authors, and to publish the prepublication paper in the PRP journal not as a
      rejection but as a correction. In order to give members of the Japan
      Prosthodontic Society a better understanding of the PRP journal, we held a Skills
      Improvement Seminar for Submitting Articles to the PRP at the 114th scientific
      meeting (Niigata) and the local branch scientific meetings. This paper summarizes
      the first half of the seminar and describes the editing work of PRP.

PMID- 16790956
TI  - [Skills Improvement Seminar for Submitting Articles to the Prosthodontic Research
      & Practice Journal. Part II. The manner to prepare and submit the scientific
      articles to English journal].
AB  - Over the last decade, research on prosthodontics has progressed and several
      academic associations and/or societies have been established. The number of
      journals published by the academic societies has increased. Prosthodontic
      Research & Practice (PRP), an official journal of the Japan Prosthodontic
      Society, was launched in 2002 and will be published quarterly from 2006. Most of
      the presentations in the scientific meetings of the Japan Prosthodontic Society
      have been buried, although the scientific quality and/or clinical values of some
      of them are relatively high. On the other hand, the reviewers of the scientific
      journal tend to review critically and severely, to maintain the quality of the
      journal. There are few review systems to improve the quality of the articles.
      Hence, the editorial board tries to make comments to improve the quality of
      submitted articles. This paper summarizes 'How to prepare scientific papers in
      English' as presented in the 'PRP Skills Improvement Seminar' at the 114th
      Scientific Meeting of the Japan Prosthodontic Society (Niigata).

PMID- 16790957
TI  - [A study on post length for fiber post and composite resin core restorations].
AB  - PURPOSE: This in vitro study investigated the use of short posts for fiber post
      and composite resin core restorations. METHODS: A replica of a human maxillary
      central incisor was prepared from bovine teeth using the CELAY system (MIKRONA,
      Switzerland). Specimens consisted of three different post lengths (2, 5, 8 mm)
      and three types of remaining coronal tooth structure (0, 0.5, 1 mm). The failure
      load and failure mode in the fiber post and composite resin core and cast metal
      post and core restorations were compared. RESULTS: There was no significant
      difference in failure load between both post and core methods with 1 mm of
      remaining coronal tooth structure. Therefore, shorter posts may be used in this
      condition. High failure loads were recorded with 5 and 8 mm post lengths that had
      0 mm of remaining coronal tooth structure in cast metal post and core
      restorations. However, there was no significant difference in failure load with
      any post length in fiber post and composite resin core restoration. A high
      failure load was recorded with 5 mm and 8 mm post lengths that had 0.5 mm of
      remaining coronal tooth structure. A long post may be required in cases with less
      coronal tooth structure. The failure mode was repairable for fiber posts with 0
      mm of remaining coronal tooth structure. However, the failure mode was impossible
      to repair in those that had 0.5 mm, 1 mm of remaining coronal tooth structure.
      CONCLUSION: This in vitro study suggested that short post lengths would be
      adequate for fiber post and composite resin core restorations. However, the
      failure mode may be impossible to repair when using a fiber post.

PMID- 16790958
TI  - [Reinforcement for overdentures on abutment teeth].
AB  - PURPOSE: This study investigated the effect of the position of reinforcement
      wires, differences in artificial teeth, and framework designs on the breaking
      strength of overdentures. METHODS: The basal surfaces of composite resin teeth
      and acrylic resin teeth were removed using a carbide bur. A reinforcement wire or
      a wrought palatal bar was embedded near the occlusal surface or basal surface.
      Four types of framework structures were designed : conventional skeleton
      (skeleton), housing with skeleton (housing), housing plus short metal backing
      (metal backing), and housing plus long metal backing (double structure). After
      the wires, bars, and frameworks were sand-blasted with 50 microm Al(2)O(3)
      powder, they were primed with a metal primer and embedded in a heat-polymerized
      denture base resin. The breaking strengths (N) and maximum stiffness (N/mm) of
      two-week aged (37 degrees C) specimens were measured using a bending test (n=8).
      All data obtained at a crosshead speed of 2.0 mm/min were analyzed by
      ANOVA/Tukey's test (alpha=0.01). RESULTS: There were no statistical differences
      between the two kinds of artificial teeth (p>0.01). The wrought palatal bar had
      significantly higher strength than the reinforcement wire (p<0.01). Greater
      strengths were found for specimens with frameworks than those without frameworks
      (p<0.01). The breaking strength of the wrought palatal bar embedded near the
      occlusal surface was higher than that on the basal surface (p>0.01). The breaking
      strength and maximum stiffness of the double structure framework were
      significantly greater (p<0.01) than those of the conventional frameworks.
      CONCLUSION: The breaking strengths of overdentures were influenced by the size
      and position of the reinforcement wires. Double structure frameworks are
      recommended for overdentures to promote a long-term prognosis without denture
      breakage.

PMID- 16790959
TI  - [Shock absorption of mouthguard materials--influence of temperature conditions
      and shore hardness on shock absorption].
AB  - PURPOSE: To consider changes in the physical properties of mouthguard materials
      with the change of temperature, shock-absorbing examination and Shore hardness
      measurement of existing MG materials and other elastic materials were carried
      out. METHODS: Both examinations were done under two temperature conditions: at
      room temperature (25 degrees C) and simulated intraoral temperature (37 degrees
      C). In addition, a comparative study of the relation between Shore hardness and
      shock absorption of the materials was made. A self-made drop impact machine was
      used for the shock-absorbing examination. The thickness of a sample was assumed
      to be 3 mm. The loading was applied by dropping 3 kinds of steel ball, phi 10 mm
      (4.0 g), phi 15 mm (13.7 g), and phi 20 mm (32.6 g) from a height of 60 cm. The
      shock absorption of all materials was compared by the maximum impact force. Shore
      hardness was measured based on the JIS standard. RESULTS: The shock absorption of
      each material showed a different tendency depending on the loading condition.
      Furthermore, the shock absorption of the same material showed different results
      depending on the temperature condition. Shore hardness measurements tended to
      show low values with the condition of 37 degrees C for all materials. CONCLUSION:
      From the relation between shock absorption and Shore hardness, it was confirmed
      that there is a correlation between hardness and the maximum impact force in the
      materials that showed shock absorption by elastic deformation. Some materials
      showed high shock absorption compared with existing MG materials.

PMID- 16790960
TI  - [Application of a jaw motion tracking device that measures six degrees of freedom
      using optoelectronic].
AB  - PURPOSE: A jaw motion tracking device that measures six degrees of freedom has
      recently been developed. Understanding jaw motion is useful, but previous
      measurement methods were impractical for use in dental clinics. The overall aim
      of this study was to demonstrate the simple operation, low cost, and high
      precision of a recently developed jaw tracking device. In addition, this study
      explored its potential clinical applications. METHODS: In this study, we compared
      two jaw motion tracking devices: a digital system type of device and an optical
      type of device. First we established a baseline occlusal plane from which to
      measure jaw motion in the same subject with both devices. The jaw motion signals
      were sampled at a frequency of 100 Hz. The subjects were three healthy women
      (mean age +/- SD = 26.3 +/- 1.2 years) who were recruited from among the crown
      and-bridge faculty of Tsurumi University of Dentistry. The jaw motions measured
      were open-close movement, sagittal border movement, and frontal border movement.
      In addition, the kinematic axis point was calculated from the sagittal border
      movement. Data from the digital system type of device and data from the optical
      device were compared. The data were selected to measure rotation and
      translocation, i.e. jaw position about protrusion, both laterotrusion and maximal
      opening of the mouth. RESULTS: The root mean square (RMS) error of position
      measurement was 0.163 mm with MM-JI-E and 0.178 mm with the optical type of
      device. The RMS error of jaw motion measurement with the optical type of device
      was maximum at 0.8mm and minimum at 0.1mm. This was similar to that with digital
      system type of jaw motion tracking device. CONCLUSION: This study showed the
      possibility of developing clinical applications for this jaw motion device.

PMID- 16790961
TI  - [Evaluation of prosthetic treatment using number of chewing strokes until
      swallowing of water absorbing rice crackers].
AB  - PURPOSE: Various methods of evaluating the ability of mastication have been
      reported, most of which involve evaluating of the ability to comminute foods. In
      this study, a new method of evaluating the ability of mastication focusing on
      bolus formation was applied to denture wearers. METHODS: One hundred and twenty
      five subjects (71 males and 54 females) using removable dentures and receiving
      follow-up in the Niigata University Hospital were selected. This group was
      categorized by Eichner's classification, and investigated for the effect of
      prosthetic treatment by counting the number of chewing strokes until the first
      swallow of rice crackers. RESULTS: It was clarified that the number of chewing
      strokes until the first swallow counted by visual observation agreed well with
      the number of chewing strokes counted by electromyogram wave of masseter muscle,
      laryngeal motion, and swallowing sound, as a preparatory experiment. Using the
      method of counting chewing strokes by visual observation, the effect of
      prosthetic treatment was evaluated, and the results were as follows. 1)There is a
      significant difference in the number of chewing strokes without dentures between
      the Eichner A group, B group, and C group. 2)There was no significant difference
      in the number of chewing strokes with dentures among the three groups. 3)A
      significant decrease in the number of chewing strokes was proven by the use of
      removable dentures. 4)Both the improvement rate of chewing strokes (the ratio of
      the number of chewing strokes with dentures until the first swallow to that
      without dentures) and the difference of chewing strokes increased significantly
      in the order of Eichner A, B, and C. CONCLUSION: It was clarified that the effect
      of prosthetic treatment can be quantitatively evaluated by counting the chewing
      strokes of rice cracker. Moreover, it was suggested that the condition of
      prosthetic treatment can be evaluated by analyzing the improvement rate of
      chewing strokes.

PMID- 16790962
TI  - [Barrel finishing of cobalt-chromium alloy cast plate--basic study on polishing
      materials and time].
AB  - PURPOSE: This study was designed to establish the optimum grinding condition of
      barrel finishing for cobalt-chromium alloy. Smoothing of the mucosal surface,
      reduction of labor, and improvement of the working environment were estimated by
      the application of barrel finishing to cobalt-chromium alloy. METHODS: Tabular
      test pieces cast in cobalt-chromium alloy whose surface was standardized by
      waterproof abrasive papers were used in this study with a centrifugal flow barrel
      finishing machine. The abrasive that was most suitable for the primary polishing
      was selected, and proper polishing time was then decided by measuring the surface
      roughness of the test pieces. The abrasive and polishing time for the secondary
      polishing were decided in the same manner. Finally, the surface texture of the
      test pieces, which were finished in this condition by the manufacturer's
      instruction or by the electrolytic polishing method, were compared. Statistic
      analysis was performed by one-way analysis of variance and the multiple
      comparison test. RESULTS: A triangular prism-shape abrasive made of Al(2)O(3) and
      SiO(2) whose one side or height was 6 mm was selected for the primary polishing,
      and the same kind of abrasive with one side or height of 4 mm was chosen for the
      secondary one. The optimum polishing time for the primary polishing and the
      secondary polishing were 60 minutes and 40 minutes, respectively. The surface
      roughness of the test pieces that were finished in this condition was
      significantly smaller than that finished following the manufacturer's indication
      or that finished by the electrolytic polishing method. CONCLUSION: The optimum
      polishing condition of barrel finishing for cobalt-chromium alloy was established
      in this study. For the polished surface of cast dentures, polishing by a rotary
      cutting instrument after barrel finishing in this condition would be needed, as
      no luster was observed on the finished surface.

PMID- 16790963
TI  - [Development of a light-polymerized resin for the record base. Part 1 Comparison
      with autopolymerizing resin].
AB  - PURPOSE: The record block for maxillomandibular registration of the denture is
      absolutely necessary in order to decide the mandibular position. This record
      block must provide sufficient strength so as not to cause deformation in the oral
      cavity. It must also fit the alveolar ridge well in order to keep accurate
      registration. Since most of the conventional materials for this purpose are not
      sufficient, a new specific light-polymerized resin was experimentally developed
      for the record base. METHODS: The mechanical strength and suitability of the new
      material were examined in comparison with a conventional autopolymerizing resin.
      RESULTS: 1) The transverse strength was equivalent to that of the
      autopolymerizing resin. 2) Although the shear bond strength was equivalent to the
      autopolymerizing resin, the intensity was drastically improved by the application
      of composite primer. 3) The light-polymerized resin and the autopolymerizing
      resin did not show any difference in suitability, and it was a clinical value
      without problem. CONCLUSIONS: From these findings, it was confirmed that the new
      light-polymerized resin had the physical property for clinical application as a
      material for the record base.

PMID- 16790964
TI  - [A review of clinical follow-up studies focusing on pretreatment conditions of
      abutment and clinical examination parameters].
AB  - PURPOSE: When patients have their teeth taken care of, one of their biggest
      concerns is how long the solution will last. Studies on the longevity or
      prognosis of bridges published so far have mainly reported on the evaluation of
      the survival rate for each kind of bridge. We believe that abutments need to be
      researched more carefully and clinically in the future. STUDY SELECTION: A
      Medline search was conducted, as well as manual searching of bibliographies from
      relevant articles. Studies reporting the survival rate were selected from the
      reports mentioning the prognosis of bridges. We mainly reviewed 1) the conditions
      of abutments before treatments and 2) applicable parameters in each case.
      RESULTS: We found no study that mentioned the detailed conditions of abutments
      before treatment using systematic evaluation parameters. Most parameters
      concerned the prosthodontics itself and bacteria. Only 21. 2% described objective
      parameters. CONCLUSION: This review indicates the necessity for establishing a
      classification of abutments based on some evidence so that the after-treatment
      conditions can be predicted from the pre-treatment conditions. It also indicates
      that we have to consider objective parameters carefully when conducting
      prospective research on the prognosis of fixed partial dentures or when
      establishing a new clinical evaluation system.

PMID- 16790965
TI  - [A case of occlusal reconstruction for disintegration of occlusion].
AB  - PATIENT: A 70-year-old male patient visited our clinic with the chief complaint
      of masticatory dysfunction due to ill-fitting upper and lower partial dentures.
      Serious periodontal disease was observed around the remaining teeth. The occlusal
      condition was crossbite due to mandibular protrusion, and the occlusal supporting
      area was classified as Eichner's B-3. A Konus telescopic denture was selected as
      a prosthesis. DISCUSSION: Dealing with the increase in occlusal force, the
      sagittal and lateral imbalances found using the Dental Prescale Occluzer system
      allowed us to minimize the damage to the prosthesis and effects on abutment teeth
      and periodontal tissue. CONCLUSION: It is vital to identify and remove early
      pathological factors of force in postoperative management to prevent the
      occurrence of new occlusal collapse in the reconstructed stomatognathic system.

PMID- 16790966
TI  - [A case report of esthetic and functional rehabilitation by a combination of
      periodontal and orthodontic treatments for advanced periodontal disease].
AB  - PATIENT: The patient was a 44-year-old woman who presented with masticatory and
      esthetic problems. She had discoloration of CR filling of a maxillary anterior
      tooth, marginal discoloration, anterior protrusion, median diastema, and closed
      bite where the mandibular anterior tooth region occluded with the maxillary
      alveolar region, tooth 8 elongation and tooth 4 defect. Periodontal and
      orthodontic treatments were therefore performed for esthetic and functional
      recovery. DISCUSSION: After prosthodontic therapy, postoperative management
      techniques are crucial, including thorough plaque control, use of a retainer to
      prevent teeth from moving back towards the original positions (Begg technique),
      muscle function therapy (improving tongue movement patterns and strengthening the
      lingual and oral sphincter muscles) and occlusal adjustment. CONCLUSION: In the
      present patient, the effectiveness of orthodontic therapy before prosthodontic
      therapy was reaffirmed: dentine can be preserved, prosthodontic therapy is easier
      to perform, and therapeutic outcomes are highly predictable.

PMID- 16790967
TI  - [A case of complete dentures with improvement of mandibular position].
AB  - PATIENT: A patient visited our hospital for fabrication of functional complete
      dentures to resolve masticatory disturbance. The case was diagnosed as edentulous
      jaws with inadequate mandibular position and movement. Therefore, new complete
      dentures were fabricated and set without reference to the old dentures.
      DISCUSSION: For the diagnosis, clinical treatment and recall, each objective
      examination was suggested to be useful. CONCLUSION: The patient was satisfied as
      a result of the improvement of denture base, mandibular position, and mandibular
      movement after informed consent.

PMID- 16790968
TI  - [A case report: treatment of an esthetically highly motivated patient with Konus
      telescope denture].
AB  - PATIENT: A 49-year-old male was referred to our hospital in February 1999,
      complaining of esthetic problems of a mandibular partial denture and poor
      retention of a maxillary denture. This case was treated with a Konus mandibular
      denture for obtaining the patient's esthetic satisfaction. DISCUSSION: The
      abutment teeth and dentures have been kept in good condition since the dentures
      were delivered six years ago. According to panorama x-ray, however, the maxillary
      alveolar ridge appears to have already started to gradually resorp. Therefore, it
      is very important to carefully check the symptoms of what is wrong with his
      teeth, dentures, and alveolar ridge during every visit. CONCLUSION: The Konus
      denture has given the patient a great satisfaction, although the potential
      symptom of maxillary alveolar ridge resorption exists.

PMID- 16790969
TI  - [A partially edentulous case, increased occlusal vertical dimension by prosthetic
      treatment].
AB  - PATIENT: A 53-year-old male presented with the chief complaint of masticatory
      disturbance caused by many teeth missing in the upper and lower jaws. There was
      extensive attrition on incisors and canines which only had occlusal contact, so
      the case was diagnosed as overclosure. To improve masticatory disturbance as the
      chief complaint, removable partial dentures were made after treating the abutment
      teeth. An adequate vertical dimension was planned in order to restore the worn
      teeth on the cast, and to arrange artificial teeth in the edentulous area.
      DISCUSSION: An anterior teeth core made as an inter-occlusal record was useful
      and the arrangement of artificial teeth in the edentulous area useful for
      estimating the adequate vertical dimension. CONCLUSION: It is important to
      diagnose an adequate vertical dimension by creating acast of the original tooth
      form in the case of prosthetic treatment of severely worn teeth.

PMID- 16790970
TI  - [A case report of a metal allergy patient whose prosthesis was identified
      allergenic by non-destructive metal element analysis and a dermatological patch
      test].
AB  - PATIENT: A 70-year-old man. Eczema of the palm (Pustulosis palmaris et
      plantaris). A positive response to chromium was identified by a dermatological
      patch test. Metal elements used in his dental restorations were analyzed by non
      destructive metal element analysis, and chromium was identified only in the
      porcelain-fused-to-metal crowns restored in his maxillary central and lateral
      incisors and canines. Resin facing crowns made of a gold, silver and palladium
      alloy were installed after those crowns were removed. DISCUSSION: With all of the
      interviews performed with this patient, identification of the allergenic
      restoration in his mouth was difficult. For this kind of metal allergy patient, a
      combination of metal element analysis of intra-oral restorations with a
      dermatological patch test seems to be very useful. CONCLUSION: This patient's
      allergic symptoms were ameliorated with minimal selective removal of his intra
      oral metal restorations by non-destructive, intra-oral metal element analysis.

PMID- 16790971
TI  - [A case report of dentures for a defective upper jaw by using the functional
      impression technique].
AB  - PATIENT: A 77-year-old male who had been treated with an upper left maxilla
      resection for a malignant carcinoma was having difficulty eating with the
      unstable denture due to a defective jaw. Since dentures made by the ordinary
      method cannot be fixed firmly to the upper jaw, the functional impression
      technique was used to produce dentures for the defected jaw. DISCUSSION: The
      patient was satisfied with his new dentures, which enabled him to masticate as
      the denture were placed in the jaw properly, with an improved fit between the
      dentures and oral mucosa. CONCLUSION: It is concluded that the functional
      impression technique of taking an impression is one of the most useful methods
      for producing dentures for defective jaws.

PMID- 16790972
TI  - [A case of combined periodontal and prosthetic treatment for enamel
      hypocalcification].
AB  - PATIENT: A 23-year-old female was seen with a major complaint involving problems
      of esthetic and masticatory function, since her posterior teeth had collapsed due
      to enamel hypocalcification. Radiographic examination suggested that many teeth
      were affected by periodontitis apicalis. DISCUSSION: Combined periodontal and
      prosthetic treatments including a crown lengthening procedure enabled us to
      fabricate esthetic and functional restorations. CONCLUSION: The crown lengthening
      procedure sometimes involves the loss of alveolar bone. In this case, however,
      the treatments were successful owing to the sufficient volume of bone available.
      As a result, the prosthesis achieved optimal plaque control. This clinical report
      describes the effectiveness of the periodontal and prosthetic treatments for
      enamel hypocalcification.

PMID- 16790973
TI  - [A case of occlusal support reconstruction with modification of occlusal plane by
      fixed prosthetic restoration including dental implant].
AB  - PATIENT: A 54-year-old female patient visited our dental office July 1997. The
      patient's chief complaint was difficulty of chewing due to loss of the right
      mandibular molars. She had a collapsed occlusal plane with loss extended over a
      long period of time. This case report describes restoration of the occlusal plane
      and occlusal supporting area by fixed prosthesis including implant-supported
      crowns. DISCUSSION: Anterior guidance and provisional restoration are useful for
      reconstruction of the occlusal plane. In a dental arch with implant-supported and
      tooth-supported crowns, periodical dental checkup and occlusal equilibration are
      very important due to the existence of biomechanically different factors.
      CONCLUSION: The patient was very satisfied with the fixed prosthesis including
      implant-supported crowns. It is thought that implant treatment improves the
      quality of life of free-end partially edentulous patients.

PMID- 16790974
TI  - [Anterior guidance reconstruction by fixed prosthesis containing bone anchored
      crown].
AB  - PATIENT: A 24-year-old female patient visited our dental office with esthetic
      complaint. Implant-supported fixed prostheses were placed on the upper right and
      left side canine area. The cusps of bone anchored crowns were made to contact
      with the lower canine cusps during mandibular translation. The patient was
      followed for 5 years with no surgical or prosthetic complications. DISCUSSION:
      Stability of the intercuspal position and reduction of lateral force are of
      importance when providing occlusal contacts for bone-anchored prosthesis in
      eccentrec relations. CONCLUSION: This case offers useful information on occlusal
      contact for implant-supported prostheses.

PMID- 16790975
TI  - [A case of oral rehabilitation using implant-supported and tooth-supported
      prostheses].
AB  - PATIENT: A 57-year-old male patient visited our dental office with complaints of
      difficulty in chewing and esthetic dissatisfaction. He had collapse of the
      anterior teeth with labial inclination of the incisors. This case report
      describes a reconstruction of the occlusal plane and occlusal supporting area by
      implant-supported and tooth-supported prostheses after periodontal and
      orthodontic treatment. DISCUSSION: Improvement of the tooth axis by orthodontic
      treatment was effective for biomechanical force and establishment of anterior
      guidance. The implant-supported and tooth-supported prostheses led long-term
      preservation of occlusion success. CONCLUSION: The implant treatment was
      effective for reconstruction of the occlusal support area and an as anchor for
      orthodontic treatment.

PMID- 16790976
TI  - In vivo visualization of estrogen receptor alpha gene promoter activity.

PMID- 16790977
TI  - Current surgical strategies for lung cancer with a focus on open thoracotomy and
      video-assisted thoracic surgery.
AB  - The surgical treatment of the lung was developed primarily for pulmonary
      tuberculosis until the 1960s but was used for primary lung cancer in the 1970s.
      The incidence of lung cancer will increase in the next 30 years worldwide, and
      the annual incidence of lung cancer in Japan is expected to increase to about
      150,000 by 2015. Over the past 50 years, pulmonologists have performed
      clinicopathological studies in an attempt to prevent lung cancer. Early detection
      became possible with such studies; as a result, the rate of detection of lung
      cancer at stage I has increased. Furthermore, the frequencies of histological
      detection of peripheral squamous cell carcinoma and adenocarcinoma have
      increased. Thoracic surgeons have developed techniques, such as limited pulmonary
      resection, and have established a minimally invasive approach to the thorax.
      These successes were followed by the development of thoracoscopic surgery.
      However, minimally invasive surgery that allows for functional preservation has
      not yet been developed. Future investigations and the refinement of technologies
      are needed.

PMID- 16790978
TI  - Frequency and effects of bacterial infection in children with influenza under
      oseltamivir treatment.
AB  - BACKGROUND: New antiviral drugs can rapidly improve the symptoms of influenza,
      but some patients still have prolonged fever and complications. The cause of the
      prolonged symptoms despite antiviral therapy remains unclear. Recent studies have
      shown a synergistic effect between influenza viruses and bacteria. This study
      investigated the frequency of bacterial infection in such patients and its
      effects on the clinical course to determine the need for antibiotics. METHODS: In
      two seasons (December 2001 through March 2002, and December 2002 through March
      2003), throat cultures were obtained from 387 patients with influenza being
      treated with oseltamivir, and clinical courses were observed. Control throat
      cultures were obtained from 109 healthy children. RESULTS: The detection rate of
      pathogens was higher in patients with influenza (54.3%) than in control (23.9%,
      p<0.001). The most common pathogen was Streptococcus pneumoniae (49.7%) in
      patients with influenza and was Haemophilus influenzae (69.2%) in controls. Of
      the patients with normal flora, 4.1% had fever for 4 or more days and showed
      pathogens in throat cultures on day 4. Of the patients with pathogen-positive
      cultures who did not receive antibiotics, 40.3% had fever for 4 or more days.
      CONCLUSION: Throat cultures obtained on the first or fourth day of treatment with
      oseltamivir were positive for pathogenic bacteria in all patients with fevers for
      4 or more days. Our observations suggest that patients with influenza and
      prolonged fever despite receiving oseltamivir should be given antibiotics.

PMID- 16790979
TI  - Significance of noninvasive diagnosis of prostate cancer with cytologic
      examination of prostatic fluid.
AB  - OBJECTIVES: While reassessing the value of exfoliative cytologic examination of
      prostatic fluid (PF) for the diagnosis of prostate cancer, we found that PF is
      easily obtained with transrectal ultrasonography during prostate biopsy and that
      cytologic examination of PF is useful for the diagnosis of prostate cancer.
      METHODS: The cohort included 53 consecutive patients who underwent transrectal
      prostate biopsy from May through September 2005. Patient age was 66.7 +/- 7.24
      years, and the mean concentration of prostate-specific antigen (PSA) was 15.1 +/-
      25.8 ng/ml. The PF for cytologic examination was obtained before biopsy, and
      Papanicolaou's staining was performed. The results of cytologic examination are
      expressed as class 1 to 5. Results of cytologic examination and prostate tissue
      pathologic examination were analyzed. Patient age, PSA levels, total prostate
      volume (TPV), and PF volume were compared with cytologic class by means of
      analysis of variance. RESULTS: The mean PF volume was 378.4 +/- 245.3 microl, and
      the mean TPV was 38.0 +/- 18.8 ml. The numbers of patient in classes 1 to 5 were
      1 (1.9%), 37 (69.8%), 11 (20.7%), 1 (1.9%), and 3 (5.7%), respectively.
      Pathologic examination showed 23 (43.4%) cases of cancer, 27 (50.9%) cases of
      benign prostatic hyperplasia, and 3 (5.7%) cases of high-grade prostatic
      intraepithelial neoplasia. All three patients with class 5 results had prostate
      cancer (Gleason score, 7 to 10). All 9 patients with a PSA level greater than 16
      ng/ml had biopsy-proven cancer, and 3 of these 9 patients (33.3%) were in
      cytology class 5. Therefore, PF cytologic examination showed a specificity of
      100% and a sensitivity of 33.3% in patients with PSA levels higher than 16 ng/ml.
      The cytologic classes differed in PSA levels (F=8.271, P=0.000) but not in
      patient age, TPV, or PF volume. CONCLUSIONS: Exfoliative cytologic examination of
      PF is a valuable, noninvasive method for detecting prostate cancer, especially in
      patients with high PSA levels.

PMID- 16790980
TI  - Incidental gallbladder cancer diagnosed during and after laparoscopic
      cholecystectomy.
AB  - With the increasingly widespread acceptance of laparoscopic cholecystectomy (LC),
      the number of cases of incidental gallbladder carcinoma (GBC) has increased;
      however, management of incidental GBC is a difficult issue in the absence of
      established guidelines. The present study aims to evaluate the treatment of
      patients with incidental GBC diagnosed with LC. We performed a 14-year review of
      10 patients with GBC discovered with LC. From April 1991 through March 2004, we
      performed LC for 1,195 patients at Nippon Medical School Main Hospital. Of these
      patients, 10 (0.83%) were found to have GBC. Seven patients were women and 3 were
      men, with a mean age of 61.4 years. Four patients had mucosal tumors (pT1a), 5
      had subserosal tumors (pT2), and 1 had a serosal lesion (pT3). Eight of the 10
      patients underwent radical surgery. Two patients with pT1a tumors underwent no
      additional surgery. All 4 patients with pT1a tumors are alive without recurrence.
      One patient with a pT2 tumor with metastases to the liver and pericholedochal
      lymph nodes found with additional resection died of recurrence of metastasis to
      the liver and lung 70 months after LC. One patient with a pT2 tumor died of
      primary lung cancer 35 months after LC. The remaining 3 patients with pT2 tumors
      are alive without recurrence 51 to 128 months after surgery. One patient with a
      pT3 tumor is alive with no recurrence for 9 months. For stage Tis or T1a tumors,
      LC is sufficient. Patients with T1b tumors should undergo liver-bed resection and
      lymphadenectomy, and patients with >pT2 tumors should undergo systematic liver
      resection with lymphadenectomy. Even when incidental GBC diagnosed with LC is
      advanced, adequate additional surgery may improve the prognosis.

PMID- 16790981
TI  - Significance of plaque disruption sites in acute coronary syndrome.
AB  - Coronary plaque disruption and subsequent thrombosis occur in both unstable
      angina (UA) and acute myocardial infarction (AMI). However, it is unclear why UA
      and AMI have different clinical courses. The purpose of this angiographic study
      was to examine whether the longitudinal plaque disruption site is a factor that
      can be used to distinguish these two conditions. Seventy-two patients with AMI or
      UA in whom ischemia- or infarct-related arteries and plaque disruption sites
      could be determined were enrolled. The plaque disruption sites were classified as
      upstream type or downstream type. The upstream type and downstream type were
      defined as plaque rupture site located proximal and distal, respectively, to the
      maximum stenosis on angiography. The frequency of the upstream type was
      significantly higher in patients with AMI (60.0%) than in patients with UA
      (18.5%). On the other hand, the frequency of the downstream type was higher in
      patients with UA (81.5%) in patients with AMI (40.0%; p<0.01). The longitudinal
      plaque disruption site may thus be a factor that can be used to distinguish these
      two diseases.

PMID- 16790982
TI  - Resection of asynchronous quadruple advanced colonic carcinomas followed by
      reconstruction with ileal interposition between the transverse colon and rectum.
AB  - We report an extremely rare case of resectable asynchronous quadruple advanced
      colonic carcinomas. Successful reconstruction was performed after resection with
      an ileal interposition between the remaining colon and rectum, and the patient
      recovered bowel function. Resections of the four colonic lesions in three
      operations allowed us to leave a portion of the large bowel and to thereby
      preserve the rectum and a portion of the transverse colon. After resection of the
      third and fourth cancer lesions, we reconstructed the large bowel with ileal
      segment interposition between the residual transverse colon and rectum, leaving a
      15-cm-long segment portion of the transverse colon. This surgical procedure is an
      option for reconstruction after left-sided colectomy.

PMID- 16790983
TI  - Internal carotid artery stenosis due to atherosclerotic plaque damage after
      whiplash injury.
AB  - Blunt traumatic occlusion or stenosis of the internal carotid artery is a rare
      complication of whiplash injury and may not be recognized until the onset of
      neurological symptoms. The clinical course can vary considerably, with regard to
      both the symptoms and the interval between injury and manifestation. A dissecting
      aneurysm and intimal tear are usually observed after blunt internal carotid
      artery injury. Atherosclerotic plaque is often observed in the cervical internal
      carotid artery and carotid bifurcation, but involvement of plaque has been
      confirmed in relatively few cases of blunt traumatic internal carotid injury. We
      describe a 58-year-old man who developed cerebral embolism due to intraplaque
      thrombus after a minor whiplash injury and was successfully treated with carotid
      endarterectomy. Because thrombosis occurred within the atherosclerotic plaque, we
      named the mechanism of this case "plaque injury".

PMID- 16790984
TI  - Combined therapy with percutaneous coronary intervention and percutaneous aortic
      valvuloplasty under mechanical support for an elderly patient with cardiogenic
      shock.
AB  - Percutaneous aortic valvuloplasty is reportedly a useful tool for the management
      of critical and severe aortic stenosis with cardiogenic shock. However, early
      percutaneous coronary intervention for cardiogenic shock is beneficial for
      elderly patients with acute myocardial infarction. We describe a patient with
      critical aortic stenosis who presented with severe coronary stenosis of the left
      main trunk and the ostium of the right coronary artery. We performed percutaneous
      coronary intervention and percutaneous aortic valvuloplasty under intra-aortic
      balloon pump and percutaneous cardiopulmonary support. After these procedures,
      the cardiogenic shock was reversed, and the patient could be weaned from both
      intra-aortic balloon pump support and percutaneous cardiopulmonary support.

PMID- 16790985
TI  - Fracture of an expandable metallic stent placed for biliary obstruction due to
      common bile duct carcinoma.
AB  - We report our second case of fracture of a SMART self-expandable metallic stent
      (Cordis Endovascular, Warren, NJ) placed to treat biliary obstruction due to an
      unresectable common bile duct carcinoma. An 82-year-old man presented with
      jaundice. Computed tomography and ultrasonography on admission demonstrated a
      mass in the lower common bile duct. The mass was identified as a common bile duct
      obstruction. A SMART stent was inserted. Ten months after stent insertion, two
      additional SMART stents were inserted to relieve obstructive jaundice due to
      occlusion of the first stent. Fourteen months after insertion of the first stent,
      endoscopic examination revealed stenosis of the duodenum due to invasion of the
      common bile duct carcinoma, prompting us to perform a gastrojejunostomy 1 month
      later. Three months after gastrojejunostomy, the patient presented with
      obstructive jaundice and cholangitis. A fracture of one of the stents was then
      discovered on plain X-ray films and percutaneous transhepatic cholangiography.
      Two SMART stents were inserted simultaneously. In conclusion, we report the
      fracture of a SMART stent placed for common bile duct carcinoma. Fracture should
      be considered as a possible complication after metallic stent insertion.

PMID- 16790986
TI  - Chronic anisakiasis of the ascending colon associated with carcinoma.
AB  - Chronic anisakiasis of the colon is rare and difficult to diagnose. We report a
      case of chronic anisakiasis associated with advanced colonic carcinoma. A 69-year
      old man was admitted for abdominal pain, diarrhea, and urticaria. Right
      hemicolectomy was performed because of an obstruction of the ascending colon and
      a palpable tumor of the right lower abdomen. The lesion was thought to be located
      in the deeper layers of the ascending colon. Preoperative examinations failed to
      detect the coexistence of anisakiasis and carcinoma of the colon. The anisakis
      was identified morphologically in the intestinal wall of the resected specimen
      and by an elevated titer of an IgE antibody specific to the parasite. Seventy
      five cases of colonic and rectal anisakiasis, including the present case, have
      been reported in Japan. This is the only reported case of anisakiasis to appear
      in association with colonic carcinoma.

PMID- 16790987
TI  - CyberKnife radiosurgery for extremity schwannomas: technical note and case
      report.
AB  - Peripheral nerve sheath tumors are uncommon. Although surgical resection remains
      the treatment of choice for most symptomatic lesions, the potential for
      intraoperative injury to the nerve is not insignificant. This concern is of
      particular relevance in those patients with a genetic proclivity to develop
      multiple peripheral nerve sheath tumors. Here we report four symptomatic
      peripheral extremity schwannomas all in 1 patient who was treated with CyberKnife
      radiosurgery. The radiosurgical Dmax in each case was between 24.4 and 25.32 Gy.
      At 1-year follow-up, patient symptoms had been ameliorated, no tumor had
      increased in size and there was no compromise in neurological function. Although
      this experience is still very preliminary, it represents the first published
      description of a peripheral nerve sheath tumor being treated with stereotactic
      radiosurgery.

PMID- 16790988
TI  - Comparative evaluation of the effects of unilateral lesion versus electrical
      stimulation of the globus pallidus internus in advanced Parkinson's disease.
AB  - OBJECTIVE: To perform a prospective analysis on the effects of unilateral lesion
      versus unilateral electrical stimulation (ES) of the globus pallidus internus
      (Gpi) in the treatment of bilateral Parkinson's disease (PD). MATERIALS AND
      METHODS: We studied 18 patients with stages III-V on the Hoehn and Yahr (H-Y)
      scale having prominent rigidity, bradykinesia and gait disturbances. Nine
      patients were treated with lesions and 9 patients with ES. Both groups were
      evaluated using the New York Parkinson's Disease Scale, the Unified Parkinson's
      Disease Rating Scale part III, and the H-Y scale and with specific items of
      tremor, rigidity and bradykinesia independently on each side. Both lesions and
      electrodes for ES were placed stereotactically in the Gpi as confirmed by
      postoperative magnetic resonance images. Significance of changes was evaluated
      with the Wilcoxon test after 3 and 6 months. Significance of intergroup
      differences was evaluated using the Mann-Whitney U test. RESULTS: Lesions and ES
      significantly decreased rigidity (p < 0.01) and bradykinesia (p < 0.005) in the
      contralateral extremities. ES significantly decreased tremor in the contralateral
      extremities (p < 0.01) and rigidity and bradykinesia ipsilaterally (p < 0.01) at
      3 months. There were no significant intergroup differences. The H-Y scale score
      showed improvement in self-sufficiency. L-DOPA dose was decreased by 31%.
      CONCLUSIONS: ES was a safer procedure and more efficient in controlling PD
      symptoms. Unilateral lesions and ES may improve bilateral symptoms to the point
      of making patients self-sufficient.

PMID- 16790989
TI  - Are complications less common in deep brain stimulation than in ablative
      procedures for movement disorders?
AB  - The side effects and complications of deep brain stimulation (DBS) and ablative
      lesions for tremor and Parkinson's disease were recorded in 256 procedures (129
      DBS and 127 lesions). Perioperative complications (seizures, haemorrhage,
      confusion) were rare and did not differ between the two groups. The rate of
      hardware-related complications was 17.8%. In ventral intermediate (Vim)
      thalamotomies, the rate of side effects was 74.5%, in unilateral Vim-DBS 47.3%,
      while in 7 bilateral Vim-DBS 13 side effects occurred. Most of the side effects
      of Vim-DBS were reversible upon switching off, or altering, stimulation
      parameters. In unilateral pallidotomy, the frequency of side effects was 21.9%,
      while in bilateral staged pallidotomies it was 33.3%. Eight side effects occurred
      in 11 procedures with pallidal DBS. In 22 subthalamic nucleus DBS procedures, 23
      side effects occurred, of which 8 were psychiatric or cognitive. Unilateral
      ablative surgery may not harbour more postoperative complications or side effects
      than DBS. Some of the side effects following lesioning are transient and most but
      not all DBS side effects are reversible. In the Vim DBS is safer than lesioning,
      while in the pallidum, unilateral lesions are well tolerated.

PMID- 16790990
TI  - Gamma knife radiosurgery for refractory epilepsy caused by hypothalamic
      hamartomas.
AB  - BACKGROUND: Hypothalamic hamartomas are associated with precocious puberty and
      chronic epilepsy characterized by gelastic seizures. The seizure disorder is
      usually refractory to most antiepileptic drugs. Gamma knife surgery has emerged
      as an alternative to microsurgical removal or radiofrequency ablation to improve
      seizure control. We present our experience with radiosurgery in 4 patients
      afflicted by this disorder. METHODS: Using gamma knife radiosurgery, 4 patients
      with intractable gelastic seizures and complex epilepsy were managed. Patient age
      varied from 5 to 29 years. The duration of symptoms was 4-28 years. A conformal
      radiosurgery plan was designed with a mean of 4.25 isocenters to cover the
      hamartoma at the 50% isodose line. A mean margin dose of 17.5 Gy was used. The
      clinical outcome was evaluated with the Engel scale. RESULTS: No complication
      occurred. After a median follow-up of 22 months, 3 patients had shown some
      improvement, with 2 attaining Engel class II status. CONCLUSION: Gamma knife
      surgery is a promising alternative to microsurgical removal for patients with
      refractory epilepsy caused by hypothalamic hamartomas.

PMID- 16790991
TI  - Cochleovestibular dysfunction in ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a rheumatic disease characterized by chronic
      inflammation. The aim of this study was to evaluate the functions of the cochlea
      and the vestibular system in patients with AS. The study group consisted of 32
      patients with AS and 30 healthy volunteers as a control group.
      Otorhinolaryngologic examinations were performed in all patients together with
      pure-tone audiometry, speech tests, impedancemetry, transient evoked otoacoustic
      emission (TEOAE) and electronystagmography (ENG). A significant difference was
      found between the 2 groups with regard to pure-tone averages at high frequencies
      in each ear (p < 0.05). The rates of reproducibility in TEOAE testing were
      significantly lower in patients with AS (p = 0.03). The signal-to-noise rates of
      the response values were lower at all frequencies in patients with AS, but a
      statistically significant difference was only observed at 2, 3 and 4 Hz (p <
      0.05). ENG revealed pathologies in 11 patients with AS (34%), 8 of which were
      central (25%) and 3 of which were peripheral (9%). No correlation was found
      between cochleovestibular dysfunction and age, sex, disease duration, activity
      and medication taken. This study demonstrated that there is an association
      between AS and cochleovestibular dysfunction.

PMID- 16790992
TI  - Thymus involution and cerebral white matter damage in extremely low gestational
      age neonates.
AB  - BACKGROUND: Among newborns who die, those who have cerebral white matter damage
      are more likely than others to have thymus involution and low thymus weights.
      OBJECTIVE: We sought to evaluate in a population of preterm newborns who did not
      die if those who developed a cerebral white matter damage (as defined by an
      echolucency) are more likely than others to have thymus involution as assessed on
      chest radiographs. METHOD: The 89 infants whose data were evaluated were born
      before the 28th week of gestation, had at least one chest radiograph within the
      first 2 days of life (to determine thymus size), and at least one cranial
      ultrasonogram to assess for white matter echolucency. RESULTS: Eighty-five
      percent of these infants had a small thymus within the first 2 weeks of life.
      Median time to thymus involution in those born before the 26th week of gestation
      was 36 h, and in those born during or after the 26th week of gestation was 140 h.
      Infants who developed involution before the median time in their respective
      gestational age groups were classified as early involuters (group 1) and were
      compared to their peers with late/no involution (group 2). Infants with an
      echolucency were more likely to have had early involution than infants without an
      echolucency (89% vs. 44%) (p = 0.01). This relationship was not distorted by
      potential confounders. The echolucency odds ratio associated with early thymus
      involution was consistently above 8 in all strata of the sample. CONCLUSION:
      These results are consistent with the possibility that early thymus involution
      and neonatal white matter damage are not independent phenomena and may have
      common antecedents.

PMID- 16790993
TI  - Stroke research priorities for the next decade--A representative view of the
      European scientific community.

PMID- 16790994
TI  - Hot spot formation in the nuclear envelope of oocytes in response to steroids.
AB  - A Glucocorticoid-sensitive cell rapidly responds to hormone stimulation with
      bidirectional exchange of specific macromolecules between cytosol and nucleus.
      Glucocorticoid-initiated macromolecules (GIMs) must overcome the nuclear envelope
      (NE) to enter or leave the nucleus. GIM translocation occurs through nuclear pore
      complexes (NPCs) that span the NE. We investigated the question whether transport
      of GIMs through NPCs occurs random or involves selected groups of NPCs (hot
      spots). Glucocorticoid receptors were expressed in Xenopus laevis oocytes and GIM
      transport was activated by triamcinolone acetonide, a potent synthetic
      glucocorticoid analogon. Glucocorticoid receptors associated with the NE and the
      chromatin were identified using western blot analysis and, at single molecule
      level, atomic force microscopy. Fluorescence-labeled dextran was used to describe
      passive NE permeability. We observed that after hormone injection (i) small GIMs,
      most likely GRs, localize within seconds on both sides of the NE. (ii) large
      GIMs, most likely ribonucleoproteins, localize within minutes on NPCs at the
      nucleoplasmic side (iii) both small and large GIMs accumulate on selected NPC
      clusters (iv) NE permeability transiently decreases when GIMs attach to NPCs. We
      conclude that GIM transport across the nuclear barrier does not randomly take
      place but is carried out by a selected population of NPCs.

PMID- 16790995
TI  - Single cell volume measurement by quantitative phase microscopy (QPM): a case
      study of erythrocyte morphology.
AB  - The measurement of the volume of intact, viable cells presents challenging
      problems in many areas of experimental and diagnostic science involved in the
      evaluation of cellular morphology, growth and function. This investigation
      details the implementation of a recently developed quantitative phase microscopy
      (QPM) method to measure the volume of erythrocytes under a range of osmotic
      conditions. QPM is a computational approach which utilizes simple bright field
      optics to generate cell phase maps which, together with knowledge of the cellular
      refractive index, may be used to measure cellular volume. Rat erythrocytes
      incubated in imidazole-buffered solutions (22 degrees C) of graded tonicity were
      analysed using QPM (n=10 cells/group, x63, 0.8 NA objective). Erythrocyte
      refractive index (1.367) was measured using a combination of phase and
      morphological data obtained from cells adopting spherical geometry under
      hypotonic conditions. Phase-computed volume increased with decreasing solution
      osmolality: 42.8 +/- 2.4, 48.7 +/- 2.3, 62.6 +/- 2.3, 90.8 +/- 7.7 microm3 in
      solutions of 540, 400, 240, and 170 mosmol/kg respectively. These volume changes
      were associated with crenated, bi-concave and spherical morphological states
      associated with increasing tonicity. This investigation demonstrates that QPM is
      a valid, simple and non-destructive approach for measuring cellular phase
      properties and volume. QPM cell volume analysis represents a significant advance
      in viable cell experimental capability and provides for acquisition of 'real
      time' data - an option not previously available using other approaches.

PMID- 16790996
TI  - PGE2-induced apoptotic cell death in K562 human leukaemia cells.
AB  - Prostaglandin-E2 (PGE2) is known to trigger suicidal death of nucleated cells
      (apoptosis) and enucleated erythrocytes (eryptosis). In erythrocytes PGE2 induced
      suicidal cell death involves activation of nonselective cation channels leading
      to Ca2+ entry followed by cell shrinkage and triggering of Ca2+ sensitive cell
      membrane scrambling with phosphatidylserine (PS) exposure at the cell surface.
      The present study was performed to explore whether PGE2 induces apoptosis of
      nucleated cells similarly through cation channel activation and to possibly
      disclose the molecular identity of the cation channels involved. To this end,
      Ca2+ activity was estimated from Fluo3 fluorescence, mitochondrial potential from
      DePsipher fluorescence, phosphatidylserine exposure from annexin binding, caspase
      activation from caspAce fluorescence, cell volume from FACS forward scatter, and
      DNA fragmentation utilizing a photometric enzyme immunoassay. Stimulation of K562
      human leukaemia cells with PGE2 (50 microM) increased cytosolic Ca2+ activity,
      decreased forward scatter, depolarized the mitochondrial potential, increased
      annexin binding, led to caspase activation and resulted in DNA fragmentation.
      Gene silencing of the Ca2+-permeable transient receptor potential cation channel
      TRPC7 significantly blunted PGE2-induced triggering of PS exposure and DNA
      fragmentation. In conclusion, K562 cells express Ca2+-permeable TRPC7 channels,
      which are activated by PGE2 and participate in the triggering of apoptosis.

PMID- 16790997
TI  - Caveolin-1 is associated with VCAM-1 dependent adhesion of gastric cancer cells
      to endothelial cells.
AB  - BACKGROUND/AIMS: Cell adhesion molecules play a critical role in the invasion and
      metastasis of a variety of human tumors. Abnormal expression of VCAM-1 has been
      demonstrated to correlate with the malignant progression of gastric tumors, but
      the molecular mechanism underlying the VCAM-1-dependent metastasis has been
      rarely investigated. To explore the role for tumor cell-expressing adhesion
      molecules in the carcinoma-endothelium adhesion, we analyzed expression status of
      adhesion molecules in gastric cancer cells and its association with tumor cell
      capability of endothelial adhesion. METHODS: Endothelial adhesion ability of
      gastric tumor cells was tested using calcein AM staining assay. Expression of
      cell surface proteins was determined by Western blot, flow cytometry, and
      immunofluorescence assays. RNAi-mediated knockdown of gene expression and
      neutralization with specific antibodies were utilized for functional analysis.
      RESULTS: One of three cell lines tested was identified to be adhesive to
      endothelial cells and express VCAM-1. Adherence ability of the cells was
      dramatically decreased by neutralization of surface VCAM-1. VCAM-1 was co
      localized with Caveolin-1 and siRNA-mediated knockdown of Caveolin-1 expression
      significantly blocked the VCAM-1-dependent cell adhesion. CONCLUSIONS: Our data
      imply important roles for VCAM-1 and Caveolin- 1 in the regulation of metastatic
      potential of gastric tumor cells.

PMID- 16790998
TI  - The leukocyte-endothelial cell interactions are modulated by extracellular matrix
      proteins.
AB  - BACKGROUND: Endothelium is supported, in normal conditions, by a basement
      membrane composed, among others, by collagen IV and laminin. Changes in the
      basement membrane composition could induce changes in endothelial cell modifying
      their interactions with leukocytes. METHODS AND RESULTS: Isolated
      polymorphonuclear cells (PMN) and peripheral blood mononuclear cells (PBMC) were
      added to cultured human umbilical endothelial cells (HuVEC) previously seeded on
      collagen IV, collagen I or gelatin. Adhesion of leukocytes to HUVEC and specific
      cytotoxicity were analysed. PMN adhesion and cytotoxicity were lower whereas
      those from PBMC were higher when HuVEC were seeded on collagen I, as compared
      with cells seeded on collagen IV. To analyse the mechanisms involved in these
      phenomena, P-selectin, ICAM-1, VCAM-1 and MCP- 1 expression were evaluated in
      HuVEC seeded on the different ECM components. P-selectin and mRNA expression of
      VCAM-1 were lower in cells seeded on collagen I. By contrast, MCP-1 expression
      was higher in collagen I. Collagen I-dependent effects were partially prevented
      when collagen I was treated with pepsin. ILK activity was lower in cells seeded
      on collagen I, whereas ERK 1/2 activity was enhanced. ILK overexpression reduced
      ERK 1/2 phosphorylation and this could promote the reduction in P-selectin and
      the increase in MCP-1. CONCLUSION: Collagen I decreased ILK activity and this
      would induce an increase in ERK 1/2 activity in HuVEC. As a consequence, the P
      selectin content is diminished and, by contrast, the MCP-1 content is increased.
      The final effect is a lower recruitment of PMN and a higher adhesion of PBMC.

PMID- 16790999
TI  - Mechanisms of neutrophil transmigration across renal proximal tubular HK-2 cells.
AB  - BACKGROUND: Adhesion of intratubular leukocytes to proximal tubules in biopsies
      of patients with rapidly progressive glomerulonephritis and the appearance of
      leukocytes in the urine in interstitial nephritis suggest interactions between
      leukocytes and tubular epithelia in renal diseases. The aim of this study was to
      investigate the effect of cytokines and endotoxin on leukocyte migration through
      proximal tubular epithelial cells and also to determine the role of the
      transmembrane adhesion molecules ICAM-1 and CD47 in this process. METHODS:
      Experiments determined transepithelial migration (TEM) of PMN (polymorphonuclear)
      leukocytes through monolayers of HK-2. Expression of ICAM-1 and CD47 was assessed
      via confocal immunofluorescence, FACS analysis and western blotting. The effect
      of antibodies against ICAM-1 and CD47 on TEM was examined. Furthermore
      measurements of cytokine release (IL- 6 and IL-8) were performed. RESULTS:
      Preincubation of HK-2 cells with either TNFalpha or LPS resulted in stimulation
      of PMN migration through monolayers of HK-2 cells. There was no preferred
      direction of transmigration. ICAM-1 was expressed by HK-2 cells and expression
      was increased after 4 h stimulation with TNFalpha or LPS. Application of ICAM-1
      antibodies inhibited TEM. CD47 was expressed in both HK-2 cells and PMN. CD47
      antibodies inhibited predominantly basolateral-to-apical TEM. HK-2 cells released
      IL-8 and IL-6 preferably into the apical compartment. Additionally, we showed
      that fMLP induced transmigration through monolayers of HK-2 cells was associated
      with significant increased CD47 expression on PMN cell surfaces. CONCLUSIONS:
      Inflammatory mediators stimulate TEM of PMN through monolayers of HK-2 cells
      without a clearly discernible preference of direction. Mechanisms involved in TEM
      stimulated by cytokines or endotoxin appear to be mainly changes in surface
      receptor densities of HK-2 cells with ICAM-1 and CD47 playing an essential role.

PMID- 16791001
TI  - The sodium channel of human excitable cells is a target for gambierol.
AB  - BACKGROUND: Gambierol is a polycyclic ether toxin with the same biogenetic origin
      as ciguatoxins. Gambierol has been associated with neurological symptoms in
      humans even though its mechanism of action has not been fully characterized.
      METHODS: We studied the effect of gambierol in human neuroblastoma cells by using
      bis-oxonol to measure membrane potential and FURA-2 to monitor intracellular
      calcium. RESULTS: We found that this toxin: i) produced a membrane
      depolarization, ii) potentiated the effect of veratridine on membrane potential
      iii) decreased ciguatoxin-induced depolarization and iv) increased cytosolic
      calcium in neuroblastoma cells. CONCLUSION: These results indicate that gambierol
      modulate ion fluxes by acting as a partial agonist of sodium channels.

PMID- 16791000
TI  - Functional characterization of wild-type and a mutated form of SLC26A4 identified
      in a patient with Pendred syndrome.
AB  - BACKGROUND: Malfunction of the SLC26A4 protein leads to prelingual deafness often
      associated with mild thyroid dysfunction and goiter. It is assumed that SLC26A4
      acts as a chloride/anion exchanger responsible for the iodide organification in
      the thyroid gland, and conditioning of the endolymphatic fluid in the inner ear.
      METHODS: Chloride uptake studies were made using HEK293-Phoenix cells expressing
      human wild type SLC26A4 (pendrin) and a mutant (SLC26A4(S28R)) we recently
      described in a patient with hypothyroidism, goiter and sensorineural hearing
      loss. RESULTS: Experiments are summarized showing the functional characterization
      of wild type SLC26A4 and a mutant (S28R), which we described recently. This
      mutant protein is transposed towards the cell membrane, however, its transport
      capability is markedly reduced if compared to wild-type SLC26A4. Furthermore, we
      show that the SLC26A4 induced chloride uptake in HEK293-Phoenix cells competes
      with iodide, and, in addition, that the chloride uptake can be blocked by NPPB
      and niflumic acid, whereas DIDS is ineffective. CONCLUSIONS: The functional
      characteristics of SLC26A4(S28R) we describe here, are consistent with the
      clinical phenotype observed in the patient from which the mutant was derived.

PMID- 16791002
TI  - Arsenic inhibits CFTR-mediated chloride secretion by killifish (Fundulus
      heteroclitus) opercular membrane.
AB  - Killifish are euryhaline teleosts that normally experience rapid changes in the
      salinity of the swim water. Acclimation to seawater is mediated by cortisol,
      which by activating glucocorticoid receptors, upregulates CFTR mediated Cl-
      secretion in the gill and operculum. Arsenic, a toxic metalloid that naturally
      occurs in the aquatic environment, has been shown to disrupt glucocorticoid
      hormone-mediated regulation of genes. Because little is known about the effects
      of environmentally relevant levels of arsenic on ion channels and salt
      homeostasis, studies were conducted to examine the effects of arsenic on the
      ability of killifish to acclimate to increased salinity. Arsenic in the swim
      water or administered by intraperitoneal injection prevented acclimation. To
      determine if arsenic blocked acclimation by inhibiting CFTR mediated Cl-
      secretion (Isc), opercular membranes were isolated and mounted in Ussing chambers
      and the effects of arsenic on Isc were measured. Arsenic (24 hr exposure) reduced
      Isc in opercular membranes isolated from salt water acclimated killifish. In
      addition, arsenic acutely (5-10 minutes) and reversibly inhibited Isc with an
      IC50 = 4.1 microM (305 ppb) when applied to the apical (seawater) side of the
      operculum, but not when added to the basolateral side of the operculum. Arsenic
      (4 microM for 60 minutes) also reduced mitochondrial respiration. Thus,
      environmentally relevant levels of arsenic block acclimation to seawater in
      killifish by reversibly inhibiting CFTR-mediated Cl- secretion by the opercular
      membrane, in part by inhibiting mitochondrial respiration.

PMID- 16791003
TI  - Human adipose tissue-derived mesenchymal stem cells improve postnatal
      neovascularization in a mouse model of hindlimb ischemia.
AB  - BACKGROUND/AIM: It has been reported that adipose tissue contain progenitor cells
      with angiogenic potential and that therapy based on adipose tissue-derived
      progenitor cells administration may constitute a promising cell therapy in
      patients with ischemic disease. In this study we evaluated the effect of culture
      expanded mesenchymal stem cells (MSC) derived from adipose tissue on
      neovascularization and blood flow in an animal model of limb ischemia in
      immunodeficient mice. METHODS: MSC were cultured from human adipose tissue by
      collagenase digestion. Hindlimb ischemia was created by ligating the proximal
      femoral artery of male nude mice. Human adipose tissue stromal cells (hADSC) were
      transplanted one day or 7 days after ligation. RESULTS: During culture expansion
      of hADSC CD34 expression was downregulated. The laser Doppler perfusion index was
      significantly higher in the CD34(-), Flk-1(-), CD31(-) ADSC-transplanted group
      than in the control group, even when cells were transplanted 7 days after
      hindlimb ischemia. Histological examination showed that hADSC transplantation
      recovered muscle injury and increased vascular density, compared with the control
      group. The effect of hADSC was correlated with the number of transplanted cells,
      but not with the ratio of CD34 expression. In vitro, hADSC can form vessel-like
      structure and express von Willibrand Factor. Conditioned media from hADSC
      increased proliferation and inhibited apoptotic cell death in of human aortic
      endothelial cells. CONCLUSION: This study showed that hADSC can be an ideal
      source for therapeutic angiogenesis in ischemic disease.

PMID- 16791004
TI  - Percutaneous coronary intervention in a patient with congenital factor XI
      deficiency and acquired inhibitor.
AB  - BACKGROUND: Factor XI deficiency has been associated with bleeding diathesis
      mostly secondary to trauma and post-operatively depending on the severity of
      deficiency. Cases with factor XI deficiency having undergone cardiac surgery and
      coronary intervention after appropriate replacement therapy have been reported in
      the past. The presence of inhibitor in factor XI deficiency poses a hematological
      challenge and literature regarding coronary intervention in such patients is
      limited. Immunosuppressive therapy, plasma exchange and factor VII product
      transfusions have been used prior to cardiac interventions in few such reported
      cases. METHOD: We report our approach in such a case of Percutaneous Transluminal
      Coronary Angioplasty in a 72-year-old male of Jewish origin who has congenital
      factor XI deficiency complicated with acquired inhibitor. RESULTS: In some cases,
      the acuity of the coronary syndrome may mandate immediate coronary intervention.
      However, patient's history of factor XI deficiency and acquired inhibitor pose a
      major dilemma of further course of action. We performed percutaneous balloon
      angioplasty in this case with no anti-coagulant and with favorable outcome.
      CONCLUSION: Under these circumstances of significant coagulation disorder and
      based on the case report, we recommend that balloon angioplasty be undertaken
      with no additional anti-coagulation other than Aspirin.

PMID- 16791005
TI  - Xenografting tumour beneath the renal capsule using modern surgical equipment.
AB  - INTRODUCTION: The growth of human tumours under the renal capsule in animal
      models has been performed in the past. However, the use of modern surgical
      equipment has not always been translated into the laboratory. We report on a
      novel method for human renal tumour transplants using an automated biopsy gun to
      obtain tumour tissue and an epidural needle with introducer to easily deploy the
      grafts under the renal capsule. METHODS: Nude mice had human xenografted tumours
      grown subcutaneously after implantation of cells from culture. Tumours were then
      biopsied using a 16-gauge automated biopsy gun. Digital calipers were used to
      measure a 2-mm segment of the biopsy core that was cut and placed inside a hollow
      needle (epidural needle). The needle was placed under the renal capsule and the
      trocar introduced to deploy the graft beneath the capsule with minimal trauma.
      Further groups had tumour harvested similarly by automated biopsy gun but had the
      implants placed subcutaneously for comparison. RESULTS: Tumour grafts were
      established in 90% of grafted kidneys in this renal subcapsular model (229.68 +/-
      118.32 mm(3); mean +/- 95% CI) which compared favourably to the subcutaneous
      model (163.81 +/- 43.3 mm(3)). Grafts were confirmed by direct observation and
      histology. CONCLUSION: Modern surgical equipment may be utilised to allow tumour
      transplantation to be precise, with an identifiable and reproducible tumour
      volume deployed. Surgical researchers and laboratory-based scientists need to
      embrace new techniques and utilise them to improve models. This model may be
      adapted to many situations in oncologic research involving xenografting.

PMID- 16791006
TI  - A simple parallel analytical method of prenatal screening.
AB  - Protein microarray has progressed rapidly in the past few years, but it is still
      hard to popularize it in many developing countries or small hospitals owing to
      the technical expertise required in practice. We developed a cheap and easy-to
      use protein microarray based on dot immunogold filtration assay for parallel
      analysis of ToRCH-related antibodies including Toxoplasma gondii, rubella virus,
      cytomegalovirus and herpes simplex virus type 1 and 2 in sera of pregnant women.
      It does not require any expensive instruments and the assay results can be
      clearly recognized by the naked eye. We analyzed 186 random sera of outpatients
      at the gynecological department with our microarray and commercial ELISA kit, and
      the results showed there was no significant difference between the two detection
      methods. Validated by clinical application, the microarray is easy to use and has
      a unique advantage in cost and time. It is more suitable for mass prenatal
      screening or epidemiological screening than the ELISA format.

PMID- 16791007
TI  - Evidence of dual pathways for lipid uptake during chylomicron remnant-like
      particle processing by human macrophages.
AB  - BACKGROUND: Though it is now clear that chylomicron remnants are pro-atherogenic
      lipoproteins, events leading to their incorporation by macrophages are poorly
      understood. METHODS: This study investigates, in human macrophages, the fate of
      either [(3)H]cholesteryl oleate or [(3)H]triacylglycerol carried by human
      apolipoprotein-E-containing chylomicron remnant-like particles (CRLP) and the
      influence of CRLP containing trilinolein, (18:2)CRLP, or triolein, (18:1)CRLP, on
      lipid accumulation, newly synthesized cholesteryl ester (CE) and triacylglycerol
      (TG). RESULTS: Labelled fatty acids from TG were markedly incorporated into TG
      and phospholipid and, to a lesser extent, into free fatty acids and were scarcely
      recovered in cholesteryl esters. [(3)H]CE from CRLP accumulated in cells in a
      dose-dependent manner with a significant difference between concentrations of 10
      and 40 microg cholesterol/ml with (18:2)CRLP. In the same concentration range, TG
      synthesis was enhanced by about 46 and 30% by (18:2)CRLP and (18:1)CRLP
      cholesterol, respectively, whereas the esterification of cholesterol, evaluated
      by [(3)H]oleate incorporation, was decreased by about 30% with both types of
      CRLP. Endocytosis inhibition did not prevent cell cholesterol and TG
      accumulation, whereas lipoprotein lipase inhibition reduced the TG content.
      CONCLUSIONS: The results are consistent with the hypotheses that in macrophages
      dietary remnants may support TG and CE internalization via different mechanisms.
      Extracellular lipolysis seems particularly important for internalization of
      dietary fatty acids, whereas the entrance of CE seems attributable to a
      concomitant selective CE uptake mediated by scavenger receptor class B type I,
      since the scavenger receptor class B type I antibody induces significant
      inhibition (38%) of [(3)H]CE transported by CRLP, but does not affect
      internalization of [(3)H]TG carried by the same particles.

PMID- 16791008
TI  - Mechanism of non-capacitative Ca2+ influx in response to bradykinin in vascular
      endothelial cells.
AB  - Bradykinin is a potent vasoactive nonapeptide. It elicits a rise in cytosolic
      Ca(2+) (Ca(2+))(i) in endothelial cells, resulting in Ca(2+)-dependent synthesis
      and release of endothelial vasodilators. In the present study, we investigated
      the mechanism of bradykinin-induced Ca(2+) influx in primary cultured rat aortic
      endothelial cells and in a mouse heart microvessel endothelial cell line (H5V).
      Bradykinin-induced Ca(2+) influx was resolved into capacitative Ca(2+) entry
      (CCE) and non-CCE. The non-CCE component was inhibited by a B2 receptor
      antagonist (HOE140; 1 microM) and a phospholipase C (PLC) inhibitor (U73122; 10
      microM). The action of bradykinin could be mimicked by 1-oleoyl-2-acetyl
      glycerol, an analogue of diacylglycerol (DAG), and by RHC80267, a DAG-lipase
      inhibitor. Immunoblots showed that TRPC6 was one of the main TRPC channels
      expressed in endothelial cells. Transfection of H5V cells with two siRNA
      constructs against TRPC6 both markedly reduced the TRPC6 protein level and, at
      the same time, decreased the percentage of cells displaying bradykinin-induced
      non-CCE. siRNA transfection also reduced the magnitude of non-CCE among the cells
      responding to bradykinin. Taken together, our data suggest that bradykinin
      induced non-CCE is mediated via the B2-PLC pathway, and that DAG may be involved
      in this process. Further, TRPC6 is one of the important channels participating in
      bradykinin-induced non-CCE in endothelial cells.

PMID- 16791009
TI  - SMART researchers plan follow-through.

PMID- 16791010
TI  - HIV tropism: diagnostic tools and implications for disease progression and
      treatment with entry inhibitors.

PMID- 16791011
TI  - The efficiency of R5 HIV-1 infection is determined by CD4 T-cell surface CCR5
      density through G alpha i-protein signalling.
AB  - OBJECTIVE AND DESIGN: The intensity of replication of CCR5-using HIV-1 strains is
      highly dependent on the number of CCR5 molecules on the surface of CD4-positive T
      cells. The molecular mechanisms responsible for this phenomenon remained so far
      unclear. As CCR5 co-receptors are coupled to G alpha i and G alpha q proteins, we
      tested the hypothesis that the activation triggered through these proteins
      secondary to the interaction between the viral envelope and CCR5 could account
      for the effect of the level of CCR5 expression on HIV-1 production. METHODS: We
      transduced the wild-type or a G-protein signalling-defective CCR5 gene into
      CD4/CCR5 HOS cells and peripheral blood mononuclear cells. The effect on cell
      activation in presence of a CCR5-binding chemokine and on HIV infection was
      monitored by measuring calcium mobilization and p24 antigen production,
      respectively. The role of G alpha i protein signalling was tested by adding
      pertussis toxin to the cell cultures or by transfecting small interfering (si)
      RNAs into the HOS cells. RESULTS: The over-expression of the wild-type form, but
      not of a G-protein signalling-defective form of CCR5, on the surface of CCR5
      expressing peripheral blood mononuclear cells markedly increased their
      infectability. In addition, both pertussis toxin and G alpha i 1-specific siRNA
      drastically inhibited R5 infection. CONCLUSIONS: The signalling through G alpha i
      protein induced upon R5 virion binding to CCR5 is responsible for the difference
      in HIV-1 infectability between CD4-positive T cells expressing low or high levels
      of cell surface CCR5 density. This observation sheds new light on the
      physiopathology of HIV infection, and opens new therapeutic opportunities
      targeting G alpha i signalling.

PMID- 16791012
TI  - Interferon-alpha differentially rescues CD4 and CD8 T cells from apoptosis in HIV
      infection.
AB  - OBJECTIVE: To examine the effects of interferon-alpha (IFN-alpha) on T cell
      survival and activation in HIV infection. DESIGN: The effects of IFN-alpha on
      spontaneous apoptosis and CD38 expression among T cell subsets were determined in
      vitro and studied in relation to CD4 cell counts, plasma HIV RNA levels and the
      age of the subjects. METHODS: Peripheral blood mononuclear cells from 48 HIV
      infected persons and 17 healthy donors were incubated in vitro overnight with or
      without the addition of IFN-alpha. Percentages of apoptotic cells (positive for
      annexin V) and CD38 cells were determined among T cell subsets. RESULTS: IFN
      alpha inhibited spontaneous apoptosis of CD4 and CD8 T lymphocytes. This
      protective activity was impaired in CD4 T cells from HIV-infected persons. The
      reduced protection of IFN-alpha among CD4 cells from HIV-infected persons was not
      related to the percentages of activated (CD38 or CD45RO+CD38+) cells.
      Surprisingly, IFN-alpha induced CD38 expression among CD8 T cells from HIV
      infected persons, and the magnitude of this effect was directly related to
      circulating CD4 T cell count. The CD8 T cell subset that expressed CD38 in
      response to IFN-alpha was defined as CD28 negative, CD62 ligand (CD62L)
      intermediate/negative. CONCLUSIONS: Heightened expression of IFN-alpha in HIV
      infection may contribute to the phenotypic activation state that characterizes
      chronic infection while a diminished responsiveness of CD4 T cells to the
      protective effect of this cytokine may contribute to differential survival of CD4
      and CD8 T cells in HIV disease.

PMID- 16791013
TI  - Virological response to a triple nucleoside/nucleotide analogue regimen over 48
      weeks in HIV-1-infected adults in Africa.
AB  - OBJECTIVES: To evaluate virologic response up to 48 weeks, and emergence of HIV-1
      resistance mutations at 24 weeks, in therapy-naive adults initiating
      zidovudine/lamivudine/tenofovir DF. DESIGN: : A cohort within the DART trial.
      METHODS: Plasma HIV-1 RNA was assayed in 300 adults with baseline CD4 cell count
      < 200 cells/mul from sites in Uganda and Zimbabwe using the Roche Amplicor assay
      v1.5. Samples with HIV-1 RNA > 1000 copies/ml at 24 weeks were sequenced in the
      pol region. RESULTS: Median baseline CD4 cell count was 101 cells/mul and HIV-1
      RNA 279,910 copies/ml (mean, 5.4 log10). At 48 weeks, 61% (165/272) had HIV-1 RNA
      < 50 and 72% (196/272) < 400 copies/ml, compared with 59% (167/281) and 79%
      (221/281) at 24 weeks. At 24 and 48 weeks, 15 and 24% respectively had HIV-1 RNA
      > 1000 copies/ml (6 and 17% > 10 000 copies/ml), and mean CD4 cell count
      increases were 103 and 127 cells/mul, respectively. Higher baseline CD4 cell
      count was the most important predictor of virological suppression at 48 weeks,
      with little effect of baseline viral load. Eighteen of 20 genotypes from week 24
      samples with HIV-1 RNA > 1000 copies/ml showed key resistance mutations in
      reverse transcriptase. Fourteen had M184V [10 with one to four additional
      nucleoside analogue mutations (NAMs)]; one had three NAMs only; and the remaining
      three had K65R. One participant with M184V had major non-nucleoside reverse
      transcriptase inhibitor-associated mutations, despite no disclosed treatment with
      this class. CONCLUSION: Zidovudine/lamivudine/tenofovir has good virological
      efficacy in advanced HIV disease. In this population, who were infected with HIV
      1 subtypes A, C or D, M184V with or without NAMs was the most common route to
      resistance, whereas K65R was identified less often.

PMID- 16791014
TI  - Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation
      with ritonavir in healthy male and female volunteers.
AB  - INTRODUCTION: Recent studies have described reduced absorption of certain
      protease inhibitors when administered with agents known to increase gastric pH.
      No clinically significant interactions between saquinavir absorption and gastric
      pH have previously been shown. We evaluated the effect of omeprazole, a proton
      pump-inhibitor, on the pharmacokinetics of the recently developed saquinavir-500
      mg formulation co-administered with ritonavir. METHODS: Eighteen healthy subjects
      (n = 6 women and 12 men) received 1000/100 mg saquinavir/ritonavir twice daily in
      an open-label study for 15 days. On days 11-15, subjects were administered
      omeprazole 40 mg daily with the morning dose. Serial plasma samples were
      collected for 12-h pharmacokinetic profiles of saquinavir and ritonavir on days
      10 and 15 and safety analysis on days 1, 4, 10, 15 and 29. RESULTS: The geometric
      mean and 95% confidence interval (CI), for the area under time-concentration
      curve (AUC; ng h/ml), trough plasma concentration (C trough; ng/ml) and maximum
      observed plasma concentration (Cmax; ng/ml) of saquinavir were 20599 (14396
      29360) and 37511 (28733-48970); 737 (482-1127) and 1521 (1039-2227); 3227 (2370
      4393) and 5611 (4507-7710) on days 10 and 15, respectively, with geometric mean
      ratios of 1.82, 2.06 and 1.75. No significant changes were observed in saquinavir
      elimination half life, ritonavir pharmacokinetic parameters or in safety
      laboratory tests. No unexpected adverse events attributed to study medication
      were noted. CONCLUSIONS: In the presence of omeprazole, total saquinavir plasma
      exposure is significantly increased (82% increase in AUC). The mechanism of this
      interaction requires elucidation. Despite the significant increase in saquinavir
      exposure, no short term toxicities were observed.

PMID- 16791015
TI  - Sustained improvement of dyslipidaemia in HAART-treated patients replacing
      stavudine with tenofovir.
AB  - OBJECTIVE: To describe the 12-month evolution of lipid profile in HIV-infected
      virologically suppressed patients substituting tenofovir for stavudine. DESIGN
      AND METHODS: 'Recover' was a prospective, multicenter, switch study conducted at
      120 HIV units across Spain designed to identify single nucleoside analogue
      substitution due to adverse events in real practice. Tenofovir substituted
      stavudine in 873 adult patients. No other substitutions were allowed. This lipid
      sub-study included 352 randomly recruited patients with complete follow-up and
      lipid parameters. MAIN OUTCOME MEASURES: Changes in fasting levels of total
      cholesterol (TC), high and low-density lipoprotein cholesterol (HDL-C and LDL-C),
      and triglycerides (TG) at 48 weeks, and their cardiovascular risk (CVR)
      translation. RESULTS: At 48 weeks, there was a sustained reduction in median TC (
      17.5 mg/dl; P < 0.001), LDL-C (-8.1 mg/dl; P < 0.001), and TG (-35 mg/dl; P <
      0.001). HDL-C remained roughly unchanged (-0.8 mg/dl). Patients with baseline
      hyperlipidaemia showed greater reductions in LDL-C (-29 mg/dl; P < 0.001) and TG
      (-76 mg/dl; P < 0.001). The greatest TG reduction was observed in patients with
      severe hyper-TG (-266 mg/dl; P < 0.001). The estimated 10-year CVR decreased in
      all patients (P < 0.001), and to a higher extent in patients with baseline
      hyperlipidaemia. There was a trend towards reduction according to the use of
      lipid-lowering agents (11.6% to 9,9%; P = non-significant). CONCLUSIONS: The
      substitution of tenofovir for stavudine causes a sustained improvement of
      dyslipidaemia. The reduction, although modest, is robust and sustained over time,
      and significantly reduces the CVR. This switch strategy is safe and contributes
      to an improvement in the lipid profile, especially TG, in HAART-treated patients.

PMID- 16791016
TI  - Grey nails predict low CD4 cell count among untreated patients with HIV infection
      in Malawi.
AB  - BACKGROUND: Alternative criteria for initiating antiretroviral therapy to CD4
      testing or clinical illness are needed in Malawi. METHOD: We tested if grey nails
      could be used to identify patients with a CD4 cell count less than 200
      cells/microl who had not yet presented with AIDS-defining illnesses. RESULTS:
      Using a set of 242 photographs we showed good inter-observer agreement for grey
      nails (kappa = 0.66; P < 0.0001) and the positive predictive value of grey nails
      for a CD4 cell count of less than 200 cells/microl was 81% (chi < 0.0001).
      CONCLUSIONS: Grey nails have been associated with HIV infection and we have shown
      significant correlation of this sign with a low CD4 cell count. For clinicians
      working in sub-Saharan Africa without access to CD4 cell count testing, grey or
      DB nails represent an additional staging sign to help identify a sub-group of
      patients likely to benefit from ART.

PMID- 16791017
TI  - The mother-to-child HIV transmission epidemic in Europe: evolving in the East and
      established in the West.
AB  - OBJECTIVES: To carry out an epidemiological analysis of the emerging epidemic in
      an Eastern European country and to compare the approach to prevention of mother
      to-child transmission (MTCT) with that in Western Europe. DESIGN: Prospective
      cohort study established in 1985 in Western Europe and extended to Ukraine in
      2000. METHODS: Data on 5967 HIV-infected pregnant women and their infants (1251
      from Ukraine and 4716 from Western/Central Europe) was analysed. Factors
      associated with transmission were identified with logistic regression. RESULTS:
      HIV-infection among pregnant women enrolled in Western European centres has
      shifted from being largely injecting drug use (IDU)-related to heterosexually
      acquired; in Ukraine IDU also gradually declined with women increasingly
      identified without specific risk factors. In Ukraine in 2000-2004 most (80%)
      women received single dose nevirapine (sdNVP) and/or short-course zidovudine
      prophylaxis [MTCT rate 4.2%; 95% confidence interval (CI), 1.8-8.0 for sdNVP with
      short-course zidovudine]; 2% (n = 27) received antenatal HAART and 33% (n = 418)
      delivered by elective caesarean section (CS); in Western European centres 72% of
      women received HAART (MTCT rate 1.0%; 95% CI, 0.4-1.9) and 66% delivered by
      elective CS during the same period. CONCLUSIONS: Our findings indicate distinct
      differences in the epidemics in pregnant women across Europe. The evolution of
      the MTCT epidemic in Ukraine does not appear to be following the same pattern as
      that in Western Europe in the 1980s and 1990s. Although uptake of preventive MTCT
      prophylaxis has been rapid in both Western Europe and Ukraine, substantial
      challenges remain in the more resource-constrained setting in Eastern Europe.

PMID- 16791018
TI  - Co-infection with HIV and hepatitis C virus in former plasma/blood donors:
      challenge for patient care in rural China.
AB  - BACKGROUND: Illegal commercial plasma donation in the late 1980s and early 1990s
      caused blood-borne infections in China. OBJECTIVES: To estimate the prevalence of
      HIV and hepatitis C virus (HCV) infections and to identify associated risk
      factors in central China with a history of illegal plasma collection activities.
      DESIGN AND METHODS: A cross-sectional study was carried out in 2004, in which all
      adult residents in four villages in rural Shanxi Province were invited for a
      questionnaire interview and testing of HIV and HCV antibodies. RESULTS: Of 3062
      participating villagers, 29.5% reported a history of selling whole blood or
      plasma. HIV seropositivity was confirmed in 1.3% of subjects and 12.7% were HCV
      positive. Their co-infection rates were 1.1% among all study subjects, 85% among
      HIV-positive subjects, and 8.7% among HCV-positive subjects. Selling plasma [odds
      ratio (OR), 22.5; 95% confidence interval (CI), 16.1-31.7; P < 0.001] or blood
      (OR, 3.1; 95% CI, 2.3-4.2; P < 0.001) were independently associated with HIV
      and/or HCV infections. Although a spouse's history of selling plasma/blood was
      not associated with either infection, the HIV or HCV seropositivity of a spouse
      was significantly associated with HIV and/or HCV infections (both OR, 3.2; 95%
      CI, 2.0-5.2 in men, 2.0-4.9 in women; P < 0.001). For men, residence in the
      village with a prior illegal plasma collection center (OR, 2.5; 95% CI, 1.7-3.7;
      P < 0.001) and for women, older age (OR, 3.4; 95% CI, 1.2-14.0; P = 0.04) were
      associated with HIV and/or HCV infections. CONCLUSIONS: HIV and HCV infections
      are now prevalent in these Chinese communities. HIV projects should consider
      screening and care for HCV co-infection.

PMID- 16791019
TI  - HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of
      vitamin A supplementation.
AB  - OBJECTIVE: To test whether post-partum vitamin A supplementation can reduce
      incident HIV among post-partum women and identify risk factors for HIV incidence.
      DESIGN: Randomized, placebo-controlled trial METHODS: Between November 1997 and
      January 2001, 14,110 women were randomly administered 400,000 IU vitamin A or
      placebo within 96 h post-partum. HIV incidence was monitored among 9562 HIV
      negative women. RESULTS: Cumulative incidence was 3.4% [95% confidence interval
      (CI), 3.0-3.8] and 6.5% (95% CI, 5.7-7.4) over 12 and 24 months post-partum,
      respectively. Vitamin A supplementation had no impact on incidence [hazard ratio
      (HR), 1.08; 95% CI, 0.85-1.38]. However, among 398 women for whom baseline serum
      retinol was measured, those with levels indicative of deficiency (< 0.7
      micromol/l, 9.2% of those measured) were 10.4 (95% CI, 3.0-36.3) times more
      likely to seroconvert than women with higher concentrations. Furthermore, among
      women with low serum retinol, vitamin A supplementation tended to be protective
      against incidence (HR, 0.29; 95% CI, 0.03-2.60; P = 0.26), although not
      significantly so, perhaps due to limited statistical power. Severe anaemia
      (haemoglobin < 70 g/l) was associated with a 2.7-fold (95%CI, 1.2-6.1) greater
      incidence. Younger women were at higher risk of HIV infection: incidence declined
      by 5.7% (2.8-8.6) with each additional year of age. CONCLUSION: Among post-partum
      women, a single large-dose vitamin A supplementation had no effect on incidence,
      although low serum retinol was a risk factor for seroconversion. Further
      investigation is required to determine whether vitamin A supplementation of
      vitamin-A-deficient women or treatment of anaemic women can reduce HIV incidence.

PMID- 16791020
TI  - Estimating sexual transmission of HIV from persons aware and unaware that they
      are infected with the virus in the USA.
AB  - BACKGROUND: New HIV infections stem from people who are aware they are HIV
      positive (approximately 75% of infected persons in the USA) and those who are
      unaware of their HIV-positive status (approximately 25%). OBJECTIVE: We estimated
      the relative contribution of these two groups in sexually transmitting new HIV
      infections to at-risk (HIV-negative or unknown serostatus) partners in the USA.
      METHODS: The parameters in the estimation included: number of people aware and
      unaware they are infected with HIV; 33% of the aware group are at low risk of
      transmitting HIV because of low/undetectable viral load; 57% relative reduction
      in the prevalence of unprotected anal and vaginal intercourse (UAV) with at-risk
      partners in persons aware (compared to unaware) they have HIV; and assumed
      differences in the average number of at-risk UAV partners in each awareness group
      (ranging from equal to twice as many in the unaware group). RESULTS: The
      proportion of sexually transmitted HIV from the HIV-positive unaware group was
      estimated to range from 0.54 (assuming no difference in average number of at-risk
      UAV partners between groups) to 0.70 (assuming twice as many at-risk UAV partners
      in the unaware group). Using the lower bounds, the transmission rate from the
      unaware group was 3.5 times that of the aware group after adjusting for
      population size differences between groups. CONCLUSION: The results indicate that
      the HIV/AIDS epidemic can be lessened substantially by increasing the number of
      HIV-positive persons who are aware of their status.

PMID- 16791021
TI  - The legacy of unhygienic plasma collection in China.

PMID- 16791022
TI  - Detection of a large T-cell reservoir able to replicate HIV-1 actively in breast
      milk.
AB  - In breast milk and paired blood samples of nine HIV-1-infected lactating women,
      we undertook a study to detect a CD4 T-cell reservoir and to investigate its
      capacity to enter viral production after activation. Breast milk-infected CD4 T
      cells have a greater capacity to produce viral particles actively than blood CD4
      T cells. This observation may explain the apparent paradox of a transmissible
      viral infection from a body fluid with a low viral concentration.

PMID- 16791023
TI  - Virological and immunological response to Combivir and emergence of drug
      resistance mutations in a cohort of HIV-2 patients in The Gambia.

PMID- 16791024
TI  - GB virus C genotype 1 is rarely transmitted vertically but acquired during
      infancy in West Africa.
AB  - Paired Ghanaian plasma and cord blood from pregnant women, alongside plasma
      samples from children aged 1 day to 70 months, were tested for GBV-C, HIV-1 RNA
      loads and anti-E2. Frequency of GBV-C vertical transmission in West Africa is
      significantly lower than in Europe, the USA or East Asia where genotype 2 or 3 is
      prevalent. While horizontal transmission appears predominant in West Africa, the
      lower viral load of African genotype 1 might explain limited vertical
      transmission.

PMID- 16791025
TI  - Seroreversion of HIV antibodies in patients with prolonged suppression of
      viraemia under HAART.
AB  - Prolonged virus suppression in chronically HIV-infected patients could
      hypothetically lead to antibody seroreversion. Eighty-four HIV-positive
      individuals with undetectable viraemia for longer than 5 years under HAART were
      examined. Only one individual, who had initiated HAART shortly after primary HIV
      infection, showed seroreversion. In contrast, the cure of hepatitis C virus (HCV)
      with interferon in 25 controls led to the loss of HCV antibodies in most cases.
      This information indirectly reflects that whereas HCV may be eradicable HIV is
      not.

PMID- 16791027
TI  - Risk factors for active tuberculosis in adults on highly active antiretroviral
      therapy in Africa.

PMID- 16791029
TI  - Young men's HIV risks in South Africa: the importance of multiple risk behaviors.

PMID- 16791028
TI  - Prevention of mother-to-child transmission of multi-drug resistant HIV-1 using
      maternal therapy with both enfuvirtide and tipranavir.

PMID- 16791031
TI  - Can India abolish the anachronistic homosexuality law to battle HIV/AIDS?

PMID- 16791035
TI  - Three-dimensional virtual model of the human temporal bone: a stand-alone,
      downloadable teaching tool.
AB  - OBJECTIVE: To develop a three-dimensional virtual model of a human temporal bone
      based on serial histologic sections. BACKGROUND: The three-dimensional anatomy of
      the human temporal bone is complex, and learning it is a challenge for students
      in basic science and in clinical medicine. METHODS: Every fifth histologic
      section from a normal 14-year-old male was digitized and imported into a general
      purpose three-dimensional rendering and analysis software package called Amira
      (version 3.1). The sections were aligned, and anatomic structures of interest
      were segmented. RESULTS: The three-dimensional model is a surface rendering of
      these structures of interest, which currently includes the bone and air spaces of
      the temporal bone; the perilymph and endolymph spaces; the sensory epithelia of
      the cochlear and vestibular labyrinths; the ossicles and tympanic membrane; the
      middle ear muscles; the carotid artery; and the cochlear, vestibular, and facial
      nerves. For each structure, the surface transparency can be individually
      controlled, thereby revealing the three-dimensional relations between surface
      landmarks and underlying structures. The three-dimensional surface model can also
      be "sliced open" at any section and the appropriate raw histologic image
      superimposed on the cleavage plane. The image stack can also be resectioned in
      any arbitrary plane. CONCLUSION: This model is a powerful teaching tool for
      learning the complex anatomy of the human temporal bone and for relating the two
      dimensional morphology seen in a histologic section to the three-dimensional
      anatomy. The model can be downloaded from the Eaton-Peabody Laboratory web site,
      packaged within a cross-platform freeware three-dimensional viewer, which allows
      full rotation and transparency control.

PMID- 16791036
TI  - Clinical results after stapedotomy: a comparison between the erbium: yttrium
      aluminum-garnet laser and the conventional technique.
AB  - OBJECTIVE: The objective of this study was to assess whether the use of the
      erbium: yttrium-aluminum-garnet (Er:YAG) laser has negative effects on inner ear
      function and to compare the short- and long-term hearing outcome of patients
      undergoing conventional stapedotomy versus laser stapedotomy. STUDY DESIGN:
      Retrospective review of prospectively collected audiometric data of patients with
      otosclerosis operated on by one experienced surgeon. SETTING: Academic tertiary
      referral center. PATIENTS: A total of 266 stapes surgeries were evaluated for
      intraoperative findings, of which 209 patients were evaluated for preoperative
      and postoperative hearing thresholds after a 6- to 452-week (mean, 22 wk)
      audiological follow-up. INTERVENTION: One hundred fifteen (43%) of the operations
      were performed conventionally, using manual perforators for stapedotomy (Group
      A); in 115 (43%) surgeries, the perforators were used in combination with the
      Er:YAG laser (Group B), and in 36 (14%) operations, the Er:YAG was used
      exclusively for footplate perforation (Group C). MAIN OUTCOME MEASURES: Pure-tone
      audiometry was performed before surgery, 2 days postoperatively (bone conduction
      only) and at 5, 26, and 57 weeks postoperatively. RESULTS: A postoperative
      temporary threshold shift of the bone conduction could be found in all groups. In
      Group C, where the laser was used exclusively for footplate perforation, this
      threshold shift was not only the most significant, but also-in contrast to the
      other groups-not totally reversible. In all techniques, a satisfactory air-bone
      gap closure could be achieved. The best long-term results (96% of the patients
      had <or=20 dB air-bone gap after 57 wk) could be found in Group B. CONCLUSION: If
      certain rules to minimize inner ear trauma are followed, the Er:YAG laser is a
      safe tool in middle ear surgery. Combining both the laser and the conventional
      technique, instead of the separate use of either technique, leads to superior
      postoperative hearing results.

PMID- 16791037
TI  - Stapes surgery: the diameter of the long process of the incus.
AB  - HYPOTHESIS: The aim of this study was to examine the long process of the incus in
      respect of its shape and its dimensions at the site of the attachment of a stapes
      prosthesis. BACKGROUND: One of the complications in stapes surgery is the erosion
      of the long process of the incus at the site of the attachment of the prosthesis,
      resulting in a fluctuating conductive hearing loss. Knowing the dimensions of the
      attachment site of the prosthesis at the long process of the incus will make it
      possible to optimize the size of the prosthesis loop. METHODS: The incus was
      obtained from 11 patients who had undergone middle ear surgery for hearing
      improvement or cholesteatoma removal. The ossicles were kept in 4%
      paraformaldehyde and were processed for histological examination after
      decalcification in ethylenediamine tetra-acetic acid. The 5-microm slices were
      stained with toluidine blue and examined in the light microscope. Using digitized
      video images of the histological slices, the diameters, circumference, and
      surface of the specimens were determined. RESULTS: The diameter of the long
      process of the incus at 1.4+/-0.28 mm from the tip, which is the average site of
      prosthesis attachment, showed an oval shape with a minimum diameter of 0.66+/
      0.05 mm, a maximum diameter of 0.81+/-0.1 mm, and a circumference of 2.46+/-0.23
      mm. CONCLUSION: The loop of a stapes prosthesis should have the following
      dimensions: diameter 0.9 mm, loop length of 2.2 mm, and opening of loop 0.7 mm.
      However, the material of the prosthesis and its malleability are also important
      factors.

PMID- 16791038
TI  - Negative effect of immediate hyperbaric oxygen therapy in acute acoustic trauma.
AB  - OBJECTIVE: The functional evaluation of the effect of the hyperbaric oxygen
      therapy (HBOT) onset time on cochlea by using distortion product otoacoustic
      emission. STUDY DESIGN: Animal study. METHODS: Twenty-four Wistar albino rats
      were divided into six groups and their right ears were directly exposed to a 110
      dB sound pressure level (1-12 kHz) white noise for 25 minutes. The first group
      was considered the control group. HBOT was started at 1 hour postexposure for the
      second group, at 2 hours postexposure for the third group, at 6 hours
      postexposure for the fourth group, at 24 hours postexposure for the fifth group,
      and at 48 hours postexposure for the sixth group. Signal-to-noise ratios (SNRs)
      were recorded before the noise exposure; immediately after the noise exposure;
      and on the 3rd, 7th, and 10th day of postexposure. RESULTS: SNRs at 6 to 8 kHz
      were significantly decreased after the acoustic trauma. The evaluation on the
      third day of postexposure showed that recovery begun in all groups except the
      group in which the HBOT was started at 1 hour postexposure. SNRs in the control
      group and HBOT groups were back to the preexposure levels at 10 days
      postexposure, except the 1- and 2-hour postexposure groups. However, in the group
      in which the HBOT was started at 1 hour postexposure, distortion product
      otoacoustic emissions were lost except at 4 kHz. The recovery of the SNRs in
      hyperbaric oxygen administration at 2 hours postexposure almost completed on the
      10th day after noise exposure. CONCLUSION: Immediate HBOT in acoustic trauma
      treatment is not necessary; on the contrary, it has an adverse effect.

PMID- 16791039
TI  - AAV-mediated delivery of the caspase inhibitor XIAP protects against cisplatin
      ototoxicity.
AB  - HYPOTHESIS: Delivery of the gene encoding X-linked inhibitor of apoptosis (XIAP)
      using an adeno-associated viral (AAV) vector can protect against cisplatin
      mediated ototoxicity. BACKGROUND: Cisplatin is a widely used chemotherapeutic
      agent with significant ototoxic side effects. One possible mechanism of toxicity
      is apoptotic death of many cochlear cell types. Acute treatment with inhibitors
      of caspases- enzymes critical for apoptosis- has been shown to prevent hearing
      loss in vivo, but is too short-acting for therapeutic use. Gene therapy provides
      a specific and chronic means of delivering potential therapeutic gents.
      Introducing an anti-apoptotic gene into the cochlea could provide long-term
      prophylaxis against the ototoxic effects of cisplatin. METHOD: Two groups of rats
      were treated with unilateral injection into the round window of AAV harboring a
      gene encoding either XIAP or green fluorescent protein (GFP). After at least two
      months of gene expression, auditory-brainstem-response (ABR) threshold shifts and
      outer-hair-cell (OHC) number were measured in these two groups of animals after
      72-hour treatment with cisplatin. RESULTS: Consistent with previous reports,
      uninjected and AAV.GFP-injected ears displayed profound ABR threshold elevations
      and OHC loss after cisplatin treatment. Ears that had been injected with AAV
      encoding XIAP, however, were significantly protected from these effects:
      cisplatin-induced ABR-threshold shift and hair-cell loss were attenuated by as
      much as 78% and 45%, respectively, when compared with contralateral (untreated)
      ears. CONCLUSION: XIAP delivery to the cochlea can protect against the
      audiometric changes and hair-cell loss associated with cisplatin ototoxicity. The
      efficacy, specificity, and duration of the protective effects make this a
      potentially attractive therapeutic paradigm.

PMID- 16791040
TI  - Flat-panel volume computed tomography for cochlear implant electrode array
      examination in isolated temporal bone specimens.
AB  - HYPOTHESIS: Flat-panel based volume computed tomography could improve cochlear
      implant electrode evaluation in comparison with multislice computed tomography.
      BACKGROUND: Flat-panel based volume computed tomography offers higher spatial
      resolution and less metal artifacts than multislice computed tomography. Both
      characteristics could improve the evaluation of challenging but important
      questions in cochlear implantation assessment, such as an exact imaging of
      cochlea, osseous spiral lamina, electrode array position, and single electrode
      contacts. These questions are not currently fully answered by multislice computed
      tomography. METHODS: Four isolated temporal bone specimens were scanned in a
      current multislice computed tomography scanner and in two experimental flat-panel
      based volume computed tomography scanners before and after cochlea implantation.
      To compare flat-panel based volume computed tomography and multislice computed
      tomography, four features were rated according to the following criteria: 1)
      visibility of the cochlea; 2) visibility of the osseous spiral lamina; 3)
      discernibility of individual electrode contacts; and 4) the ability to determine
      the electrode array position relative to scala tympani and scala vestibuli. Layer
      by-layer microgrinding pictures were used as the ground truth for verification of
      imaging findings. RESULTS: Flat-panel based volume computed tomography was
      superior to multislice computed tomography in all four features rated. The
      cochlea and facial nerve canal were much better delineated in flat-panel based
      volume computed tomography. The osseous spiral lamina and single electrode
      contacts were only visible in flat-panel based volume computed tomography.
      Assessment of implant position with regard to the cochlear spaces was
      considerably improved by flat-panel based volume computed tomography. CONCLUSION:
      Cochlear implantation assessment could be improved by flat-panel based volume
      computed tomography and, therefore, would be highly beneficial for cochlea
      implantation research and for clinical evaluation. However, these first results
      were shown by scanning isolated temporal bone specimens; scanning whole human
      skull bases might be more challenging.

PMID- 16791041
TI  - Change of phonation control after cochlear implantation.
AB  - OBJECTIVE: To assess the influence of acquired auditory control on some voice
      parameters in deaf children and adults after cochlear implantation. STUDY DESIGN:
      Prospective clinical study. SETTING: Tertiary referral center. PATIENTS: Twenty
      nine prelingually deafened children and 11 postlingually deafened adults.
      INTERVENTIONS: The samples of a vowel /a/ were analyzed with an Multi-Dimensional
      Voice Program (Kay Elemetrics Corporation, Lincoln Park, NJ) before and 6 to 12
      months after the cochlear implantation. MAIN OUTCOME MEASURES: The average
      fundamental frequency (F0), the short-term variation of F0 (JIT) and the
      amplitude (SH), the very long-term variation of F0 (vF0) and the amplitude (vAm),
      and the noise-to-harmonic ratio (NHR) were determined and compared for both age
      groups. The results of the acoustic analysis performed before the implantation
      were compared with the results after the implantation for children and adults.
      RESULTS: Significantly greater JIT, SH, vF0, and vAm were detected in the
      children than in the adults before and after the implantation. The prelingually
      deafened children significantly improved the control of their phonation after 6
      to 12 months' use of the cochlear implant (JIT: p=0.014, SH: p=0.011, vF0:
      p=0.014, vAm: p=0.031). In the postlingually deafened adults, no significant
      improvement was found in any of the studied voice parameters after the
      implantation. F0 showed little or no change after the implantation in children
      and adults. CONCLUSION: As expected, the voice quality of the prelingually
      deafened children was significantly worse than that of the postlingually deafened
      adults. After cochlear implantation, the children significantly improved their
      short-term and long-term F0 and amplitude variability. In adults, no significant
      improvement was detected. We suppose that the improvement is a consequence not
      only of the acquired hearing control but also of the adaptation ability of
      neuromuscular phonation control and the maturing of these control mechanisms in
      children. In adults, better phonation quality in general and lesser improvement
      after the implantation can be the results of well-developed and stable phonation
      patterns.

PMID- 16791042
TI  - D-JNKI-1 treatment prevents the progression of hearing loss in a model of
      cochlear implantation trauma.
AB  - HYPOTHESES: 1) Hearing loss caused by electrode insertion trauma has both acute
      and delayed components; and 2) the delayed component of trauma-initiated hearing
      loss can be prevented by a direct delivery of a peptide inhibitor of the c-Jun N
      terminal kinase cell death signal cascade, that is, D-JNKI-1, immediately after
      the electrode insertion within the cochlea. BACKGROUND: Acute trauma to the
      macroscopic elements of the cochlea from electrode insertion is well known. The
      impact of trauma-induced oxidative stress within injured cochlear tissues and the
      efficacy of drugs (e.g., D-JNKI-1) to prevent apoptosis of damaged hair cells is
      not well defined. METHODS: Hearing function was tested by pure-tone evoked
      auditory brainstem responses (ABRs) and distortion products of otoacoustic
      emissions (DPOAEs). D-JNKI-1 in artificial perilymph (AP) or AP alone was
      delivered into the scala tympani immediately after electrode trauma and for 7
      days. Controls were nontreated contralateral and D-JNKI-1-treated ears without
      electrode insertion trauma. RESULTS: There was no increase in the hearing
      thresholds of either the contralateral control ears or in the D-JNKI-1 without
      trauma animals. There was a progressive increase in ABR thresholds and decrease
      in DPOAE amplitudes after electrode insertion trauma in untreated and in AP
      treated cochleae. Treatment with D-JNKI-1 prevented the progressive increase in
      ABR thresholds and decrease in DPOAE amplitudes that occur after electrode
      insertion trauma. CONCLUSION: Hearing loss caused by cochlear implant electrode
      insertion trauma in guinea pigs has both acute and delayed components. The
      delayed component can be prevented by treating the cochlea with D-JNKI-1.

PMID- 16791043
TI  - Cochlear implantation in patients with neurofibromatosis type 2 and bilateral
      vestibular schwannoma.
AB  - OBJECTIVE: To investigate the results of cochlear implantation in patients with
      neurofibromatosis Type 2 (NF2) and bilateral vestibular schwannoma. STUDY DESIGN:
      Retrospective case review. SETTING: Three academic tertiary referral centers.
      PATIENTS: Seven patients with NF2 and bilateral vestibular schwannoma who lost
      hearing in at least one ear after treatment of their tumor (surgery or radiation
      therapy). INTERVENTION: Cochlear implantation after treatment of their vestibular
      schwannoma. MAIN OUTCOME MEASURE: Postimplantation audiometric scores (pure-tone
      average thresholds, consonant-nucleus-consonant (CNC) words/phonemes, Central
      Institute for the Deaf (CID) sentences, Hearing in Noise Test (HINT) quiet/noise,
      and Monosyllable, Trochee, Spondee (MTS) recognition/category tests), patient
      satisfaction, and device use patterns. RESULTS: The average age at implantation
      was 40 years (range, 16-57 yr). Follow-up ranged from 6 to 88 months after
      implantation. Three patients were implanted with residual useful hearing in the
      contralateral ear, whereas four patients had no hearing in the contralateral ear.
      Hearing loss was due to surgical excision of tumor (n=5) or gamma-knife
      radiotherapy (n=2). Postactivation pure-tone average thresholds in the implanted
      ear ranged from 30 to 55 dB (average, 32.5 dB), although speech reception testing
      varied considerably among subjects. Despite this variability, all patients
      continue to use the device on a daily basis. CONCLUSION: In selected cases of
      deafness in patients with NF2 where there has been anatomic preservation of the
      auditory nerve after acoustic neuroma resection or radiation therapy, cochlear
      implantation may offer some improvement in communication skills, including the
      possibility of open-set speech communication in some patients. These results
      compare favorably to the auditory brainstem implant offering an alternative for
      hearing rehabilitation in patients with NF2.

PMID- 16791044
TI  - Output vibration measurements of bone-anchored hearing AIDS.
AB  - HYPOTHESIS: Different bone-anchored hearing aids (BAHAs) processors have
      different output vibration characteristics, which depend on the mechanical load
      and the volume setting. Responses will differ between live heads and dry or
      plastic skulls. BACKGROUND: The BAHA is an implantable bone-conduction device.
      Three different BAHA models are available. Their output vibrations have not been
      reported using a noncontact method with differing impedance loads, including the
      BAHA-fitted patient head. METHODS: Using a laser-Doppler vibrometer, vibration
      responses with sound input of 70- to 80-dB sound pressure level were measured on
      unloaded BAHAs, a dry skull, a plastic skull, and on the abutments of three live
      BAHA-fitted patients. Responses at different volume settings and distances from
      the vibrator were also tested. Frequency responses were calculated for
      displacement, velocity, and acceleration. RESULTS: Unloaded BAHA accelerations
      were approximately 30 to 50 dB higher than live-head accelerations. Live-head
      accelerations were similar to dry skulls in frequencies of more than 500 Hz, but
      much higher than the plastic skull responses. Live-head responses were more
      damped. The Cordelle II outperformed the other two processors by approximately 20
      dB. The Classic 300 had better low-frequency responses than the Compact. The
      volume settings had little effect on vibration output overall. Acceleration peak
      was at approximately 2.5 kHz for all conditions. CONCLUSION: The BAHA processors
      differ in the output acceleration they can achieve with differing loads. The
      volume control setting has little impact on accelerations produced for most
      processors. The live-head responses are similar to the dry skull in frequencies
      of more than 500 Hz.

PMID- 16791045
TI  - Posterior canal dehiscence syndrome caused by an apex cholesteatoma.
AB  - OBJECTIVE: To compare audio-vestibular findings caused by a dehiscence of the
      posterior semicircular canal with those found in the superior canal dehiscence
      syndrome. STUDY DESIGN: Case report. SETTING: University hospital, tertiary
      referral center. PATIENT: The 44-year-old woman suffered from a gradual hearing
      loss with pulse-synchronous tinnitus as well as sound and pressure-induced
      vertigo. INTERVENTION: Audio-vestibular testing and high-resolution computed
      tomography. MAIN OUTCOME MEASURE: The superior canal dehiscence syndrome is
      caused by failure of normal postnatal bone development in the middle cranial
      fossa leading to absence of bone at the most superior part of the superior
      semicircular canal. The typical features for this syndrome are sound- and
      pressure-induced vertigo with torsional eye movements, pulse synchronous tinnitus
      and apparent conductive hearing loss in spite of normal middle-ear function. We
      present a patient with very similar symptoms and findings who, instead, had a
      posterior semicircular canal dehiscence caused by an apex cholesteatoma.
      CONCLUSION: Patients with semicircular canal dehiscence have common auditory
      vestibular features regardless of which of the two vertical semicircular canals
      is affected. The only obvious difference between the two is the vertical
      component of the sound and pressure-induced eye movements (which beats in
      opposite directions).

PMID- 16791046
TI  - Diagnostic value of vestibulo-ocular reflex parameters in the detection and
      characterization of labyrinthine lesions.
AB  - OBJECTIVE: To evaluate the power of various parameters of the vestibulo-ocular
      reflex (VOR) in detecting unilateral peripheral vestibular dysfunction and in
      characterizing certain inner ear pathologies. STUDY DESIGN: Prospective study of
      consecutive ambulatory patients presenting with acute onset of peripheral vertigo
      and spontaneous nystagmus. SETTING: Tertiary referral center. PATIENTS: Seventy
      four patients (40 females, 34 males) and 22 normal subjects (11 females, 11
      males) were included in the study. Patients were classified in three main
      diagnoses: vestibular neuritis: 40; viral labyrinthitis: 22; Meniere's disease:
      12. METHODS: The VOR function was evaluated by standard caloric and impulse
      rotary tests (velocity step). A mathematical model of vestibular function was
      used to characterize the VOR response to rotational stimulation. The diagnostic
      value of the different VOR parameters was assessed by uni- and multivariable
      logistic regression. RESULTS: In univariable analysis, caloric asymmetry emerged
      as the most powerful VOR parameter in identifying unilateral vestibular deficit,
      with a boundary limit set at 20%. In multivariable analysis, the combination of
      caloric asymmetry and rotational time constant asymmetry significantly improved
      the discriminatory power over caloric alone (p<0.0001) and produced a detection
      score with a correct classification of 92.4%. In discriminating labyrinthine
      diseases, different combinations of the VOR parameters were obtained for each
      diagnosis (p<0.003) supporting that the VOR characteristics differ between the
      three inner ear disorders. However, the clinical usefulness of these
      characteristics in separating the pathologies was limited. CONCLUSION: We propose
      a powerful logistic model combining the indices of caloric and time constant
      asymmetries to detect a peripheral vestibular loss, with an accuracy of 92.4%.
      Based on vestibular data only, the discrimination between the different inner ear
      diseases is statistically possible, which supports different pathophysiologic
      changes in labyrinthine pathologies.

PMID- 16791047
TI  - Transcanal approach to the singular nerve.
AB  - OBJECTIVES/HYPOTHESIS: Intractable benign paroxysmal positional vertigo is rare,
      and surgery is indicated in only a very small number of cases. Transcanal
      singular neurectomy is considered a difficult and risky procedure possibly
      leading to hearing loss and vertigo. The objective of this study was to evaluate
      the feasibility of the singular neurectomy through the external ear canal in an
      attempt to explain the contradictory results of previous reports of anatomists
      and of surgeons who abandoned the technique, considering that the singular
      neurectomy could not be reached via the external auditory canal without damaging
      the labyrinth. MATERIALS AND METHODS: Anatomical study on 100 halves of human
      heads in which the canal of the singular nerve (SN) was identified and opened at
      its extremities, the internal auditory canal and the ampulla of the posterior
      semicircular canal, via a posterior fossa approach. Next, the canal of the SN was
      dissected via the external auditory canal, at the floor of the round window (RW)
      niche. The relation of the SN canal to the ampulla of the posterior semicircular
      canal was evaluated. RESULTS: In 90 cases, the canal was transected medially to
      and away from the ampulla of the posterior semicircular canal, and in 8, at its
      emergence from the posterior ampullary recess. In these 98 cases, the RW membrane
      and the bony labyrinth were kept intact. In two cases, the canal of the SN could
      not be reached at the floor of the RW niche. CONCLUSION: Singular neurectomy is
      feasible via the external auditory canal, without damaging the RW membrane or the
      labyrinth in 98% of the cases. Because singular neurectomy is indicated in a very
      small number of cases, it is difficult to master this particular surgical
      procedure. This may explain why most surgeons abandoned the technique after a few
      attempts, followed by an unacceptable rate of sensorineural hearing loss.

PMID- 16791048
TI  - The natural history of vestibular schwannoma.
AB  - OBJECTIVE: The incidence of vestibular schwannomas (VSs) approaches 20 per
      million/yr. As treatment may depend on tumor growth, there is a demand of a
      treatment strategy based on hard data on the growth pattern of these tumors. This
      article reports growth data registered prospectively in 552 patients. STUDY
      DESIGN: Of the 1,818 consecutive patients, diagnosed with VS during the period
      from 1975 to 2005, 729 patients were allocated to observation by repetitive
      magnetic resonance imaging. At least two scans had been performed in 552 patients
      at the time of data analysis. Two hundred thirty patients had a tumor confined to
      the internal acoustic meatus, whereas 322 patients had a tumor with an
      extrameatal extension. Growth to extrameatal extension was the definition for
      growth in intrameatal tumors, whereas a largest diameter change of more than 2 mm
      was the criteria for growth/shrinkage of extrameatal tumors. The mean observation
      time was 3.6 years (range, 1-15 yr). RESULTS: Seventeen percent of the
      intrameatal tumors grew, whereas significantly more of the extrameatal tumors
      displayed growth during the period (28.9%). Growth occurred within the first 5
      years after diagnosis. No correlation could be demonstrated between tumor growth
      rate, sex, or age. CONCLUSION: VS growth occurs within the first 5 years after
      diagnosis in a limited number of tumors, primarily in tumors with an extrameatal
      extension. We found no relation between tumor growth and sex or age. These
      findings justify primary observation of small tumors. A treatment strategy is
      proposed for this disease, focusing on the patient group allocated to
      observation.

PMID- 16791049
TI  - Cerebrospinal fluid cytology to aid the diagnosis of cerebellopontine angle
      tumors.
AB  - OBJECTIVE: To determine if cerebrospinal fluid (CSF) cytology can be useful in
      the workup of patients with internal auditory canal/cerebellopontine angle
      (IAC/CPA) tumors and facial paralysis to diagnose metastatic disease before
      surgical intervention. STUDY DESIGN: Retrospective case series. SETTING: Tertiary
      referral center. PATIENTS: Patients who presented with or developed facial
      paralysis and IAC/CPA tumors. OUTCOME MEASURE: Lumbar puncture and CSF
      cytological analysis. RESULTS: Seven patients presented with or developed high
      grade facial paralysis (greater than House-Brackmann Grade II). In the first
      patient, excision of the tumor revealed adenocarcinoma. All subsequent patients
      were evaluated with CSF cytological analysis. In five of these patients,
      cytological CSF analysis revealed malignant cells, suggesting a diagnosis of a
      metastatic lesion rather than acoustic neuroma. Primary neoplasms were identified
      in all but one of these patients. A sixth patient had metastatic breast cancer,
      but negative CSF cytology and a stable CPA tumor after radiation treatment. Two
      patients who were being conservatively followed up for their IAC/CPA tumor
      developed a nonprogressive but persistent mild Grade II facial weakness and
      underwent CSF analysis which tested negative. One patient had surgical resection
      with pathologic findings consistent with a typical acoustic schwannoma, and the
      other patient has been conservatively followed up without change. CONCLUSION: Our
      experience suggests that patients presenting with IAC/CPA tumors and progressive
      facial paralysis of House-Brackmann Grade III or greater should have a CSF
      cytological examination before surgical intervention to evaluate for a malignant
      process.

PMID- 16791050
TI  - Lipomatous hemangiopericytoma of the skull base and parapharyngeal space.
AB  - OBJECTIVE: To discuss the diagnosis and clinical management of lipomatous
      hemangiopericytoma. STUDY DESIGN: Case report. SETTING: Tertiary referral center.
      PATIENT: A 36-year-old woman was encountered with symptoms of facial numbness,
      blurred vision, headache, and lightheadedness of 6 weeks' duration. Magnetic
      resonance imaging revealed a 5.0-cm mass in the right parapharyngeal space and
      skull base extending inferiorly to the level of the carotid bifurcation. The mass
      was consistent radiographically with a glomus jugulare tumor, and surgical
      extirpation was performed. INTERVENTION: The patient underwent a transtemporal
      approach to the right posterior fossa and jugular foramen including mastoidectomy
      and isolation and preservation of Cranial Nerves VII, X, XI, and XII. Microscopic
      analysis of the mass revealed a highly cellular spindled mesenchymal tumor with a
      pericytoma pattern. Almost half of the mass displayed a mature lipomatous
      component. These findings were consistent with a lipomatous hemangiopericytoma.
      RESULTS: The authors describe the first case of lipomatous hemangiopericytoma
      involving the skull base. This rare variant of the more common hemangiopericytoma
      has been described previously in the retroperitoneal and lower extremities.
      Although one case of lipomatous hemangiopericytoma has been described in the
      occipital region, this is the first report of this entity involving the
      parapharyngeal space, skull base, and jugular foramen. CONCLUSION: The authors
      demonstrate that lipomatous hemangiopericytoma can occur in the parapharyngeal
      space and skull base. Once thought to be an aggressive variant, this tumor has an
      extremely low propensity for distant or local recurrence. Adjuvant therapies such
      as radiation and chemotherapeutic agents are reserved for recurrent or metastatic
      lesions.

PMID- 16791051
TI  - The personal and scientific feud between Ernst Brucke and Josef Hyrtl.
AB  - OBJECTIVE: To describe the events surrounding the personal and professional feud
      between Josef Hyrtl and Ernst Brucke and its impact on early investigations into
      the function of the semicircular canals of the inner ear. DATA SOURCES: Published
      data in scientific journals and news media, documents at the Vienna Institute for
      the History of Medicine, published personal letters, and an interview with
      Brucke's great-grandson, Dr. Thomas Brucke. CONCLUSION: Although Hyrtl was
      instrumental in recruiting Brucke to the University of Vienna, the two professors
      soon became embroiled in a feud that persisted throughout their academic careers.
      The difference in approach of these two giants in their field is well illustrated
      by their views on the function of the semicircular canals of the inner ear. Based
      on their shape, Hyrtl concluded that they were important for directional hearing,
      whereas based on animal experiments, Brucke concluded that they were sense organs
      for equilibrium.

PMID- 16791052
TI  - Temporal bone brain herniation.

PMID- 16791053
TI  - Sonotubometry.

PMID- 16791054
TI  - Notice of redundant publication. Tympanic membrane healing process and
      biocompatibility of an innovative absorbable ventilation tube.

PMID- 16791056
TI  - Ball-and-socket ankle.

PMID- 16791057
TI  - The Ilizarov method for the treatment of resistant clubfoot: is it an effective
      solution?
AB  - The resistant clubfoot deformity presents a significant challenge. Several
      corrective procedures have been described, with the goal to provide a pain-free,
      plantigrade foot. The Ilizarov method of external fixation and gradual
      distraction has been reported as an alternative to conventional techniques.
      Previous reviews have concluded that this method can provide satisfactory
      correction and outcome. This study presents a review of 21 resistant clubfeet in
      17 patients, who had undergone previous surgery, treated with Ilizarov external
      fixation and gradual distraction by 1 of 2 surgeons. Outcome measures were graded
      based on function and presence of residual deformity: (a) excellent (painless,
      plantigrade foot, with no functional limitations); (b) good (plantigrade foot in
      a patient able to ambulate long distances with mild pain; (c) fair (mild residual
      deformity, required bracing, and/or had some functional limitations but an active
      life); and (d) poor (significant residual deformity, pain, and activity
      limitations). Radiographic measures of the talocalcaneal and talo-first
      metatarsal angles were compared preoperatively and postoperatively. At an average
      follow-up of 6.64 years (range, 2.25-10.50 years), 9.5% (2) achieved an excellent
      result; 4.8% (1), good; 33.3% (7), fair; and 52.4% (11), poor. All 11 of the feet
      graded poor required revision surgery at an average of 5.63 years postoperatively
      (range, 2.67-10.2 years). Only the talo-first metatarsal angle displayed a
      clinically and statistically significant correction. We conclude that the
      Ilizarov method for treatment of resistant clubfoot deformities results in poor
      outcome associated with residual or recurrent deformity, often requiring revision
      surgery.

PMID- 16791058
TI  - Prevalence of Charcot-Marie-Tooth disease in patients who have bilateral
      cavovarus feet.
AB  - It is not uncommon to see a patient with bilateral cavovarus feet in the
      outpatient setting. A large percentage of these patients are subsequently
      diagnosed with an associated condition, such as Charcot-Marie-Tooth disease. The
      purpose of the present report was to determine the prevalence of Charcot-Marie
      Tooth disease in children who have bilateral cavovarus feet. A chart review of
      children with bilateral cavovarus feet was done. Patients were excluded if they
      had an existing medical problem known to be associated with bilateral cavovarus
      feet. Charcot-Marie-Tooth disease was diagnosed after a clinical assessment by an
      orthopaedic surgeon and a neurologist. The diagnosis was confirmed by either
      standard nerve conduction velocity studies and/or the CMT DNA Duplication
      Detection Test (Athena Diagnostics Inc, Worchester, MA). A positive family
      history was noted only if the diagnosis had been confirmed by a nerve conduction
      velocity study and/or CMT DNA Duplication Detection Test. One hundred forty-eight
      patients met the study criteria. The probability of a patient with bilateral
      cavovarus feet being diagnosed with Charcot-Marie-Tooth disease, regardless of
      family history, was 78% (116 patients). A family history of Charcot-Marie-Tooth
      disease increased the probability to 91%. It is recommended that all patients
      with bilateral cavovarus feet, especially with a known family history, be
      investigated for Charcot-Marie-Tooth disease.

PMID- 16791059
TI  - Multiplier method for predicting adult foot length.
AB  - Lower and upper limb lengths and total height can be predicted by the multiplier
      method. The multiplier is a coefficient that corresponds to each age and gender.
      The coefficient for any age can be multiplied by the length at that age to give
      the length at skeletal maturity. Our purpose was to calculate foot length
      multipliers and determine whether they are independent of percentile, much like
      the multipliers for lower and upper limb lengths and total height. Foot length
      multipliers were calculated from 3 separate previously published databases of
      foot length in children. The multipliers were calculated by dividing foot length
      at maturity by foot length at each respective age for each percentile and for
      both genders. The multiplier values for each percentile group at each age were
      found to be relatively equivalent, with little variability (as was found for the
      validated multipliers for lower limb length and total height). Also, little
      variability was found among multipliers calculated from different databases. In
      addition, we compared foot length multipliers with lower limb, upper limb, and
      total height multipliers. Compared with lower limb (tibial and femoral)
      multipliers, the foot length multipliers were significantly different because the
      foot achieves a higher percentage of maturity length earlier than does the femur
      or tibia. Because prediction of limb length and limb length discrepancy can be
      achieved accurately by using the lower limb multiplier, it is also likely that
      the foot length multiplier can be used to predict foot length and foot length
      discrepancy at maturity.

PMID- 16791060
TI  - Isolated congenital pseudarthrosis of the fibula: clinical course and optimal
      treatment.
AB  - The purposes of this study were to determine the clinical course of isolated
      congenital pseudarthrosis of the fibula (ICPF) and to establish optimal treatment
      guidelines for this disease. Thirteen fibulae in 12 patients with ICPF were
      followed for an average of 6.2 years. Twelve of the 13 fibulae were regarded to
      originally have had a pre-pseudarthrotic condition. Five fibulae remained intact
      during follow-up, but 8 developed pseudarthrosis. Two cases with established
      pseudarthrosis were observed for ankle alignment change without intervention, and
      in 4 cases successful fibular osteosynthesis maintained the ankle alignment. The
      remaining 2 adolescent cases presenting with ankle valgus were treated using the
      Ilizarov technique and distal tibiofibular synostosis. ICPF follows a unique
      clinical course, which should be taken into consideration along with fibular
      status, ankle alignment, and patient age when planning treatment.

PMID- 16791061
TI  - Articular cartilage defects of the distal femur in children and adolescents:
      treatment with autologous chondrocyte implantation.
AB  - PURPOSE: Procedures aimed at biologically repairing cartilage injuries may have
      the greatest potential benefit in young patients because of their long-life
      expectancy and high-functional demands. Most cartilage-repair studies focus on
      older patient populations. This study assesses the outcomes of patients who were
      treated with autologous chondrocyte implantation before the age of 18. STUDY
      DESIGN: This is a Registry-based, multicenter, observational, cohort study of 37
      patients from whom follow-up data was prospectively collected. Patient-rated
      assessments of overall condition, pain, and swelling were measured using
      modified, 10-point scales of the Cincinnati Knee Rating System. RESULTS: Mean age
      was 16 years (11-17); 22 boys and 15 girls. Twenty-three patients underwent at
      least 1 cartilage repair procedure before the cartilage harvest, including 11 who
      had a marrow stimulation procedure. Fourteen patients were diagnosed with
      osteochondritis dessicans lesions. Thirty-five patients had single defects (mean
      size, 5.4 cm). Thirty-two patients completed self-evaluations at a minimum of 2
      years after implantation (mean follow-up = 4.3 years). The mean change in scale
      scores measuring overall condition, pain, and swelling were 3.8, 4.1, and 3.4
      points, respectively. One patient had an implantation that failed. CONCLUSIONS:
      Results highlight significant clinical improvements from baseline to follow-up
      for 32 patients who submitted follow-up data, including 28 patients who reported
      a minimum 1-point improvement in the overall condition score. CLINICAL RELEVANCE:
      These results suggest that autologous chondrocyte implantation may be an
      effective option for children and adolescents with large symptomatic chondral
      lesions of the distal femur.

PMID- 16791062
TI  - Treatment of recurrent patellar instability with a modification of the Roux
      Goldthwait technique.
AB  - Recurrent instability of the patella may be a significant disability in the
      childhood and adolescent population. Numerous surgical procedures to address this
      instability have been described, with variable outcome. This has led to
      considerable confusion in the literature as to how to treat patellofemoral
      problems in children. This study retrospectively reviews 30 knees in 20 patients
      with chronic recurrent patellar instability who were treated with a modified Roux
      Goldthwait technique including the release of contracted lateral structures by a
      single surgeon over a 13-year period, with an average of 6.2 years follow-up. By
      Insall's criteria, 26 knees had an excellent result, 3 good result, and 1 fair
      result. Ten patients evaluated using a dynamometer showed that strength achieved
      in the operated leg was greater than 90% in 8 patients and greater than 80% in 2
      patients. Here, we report upon a single operation to treat patellar instability
      performed in the pediatric population with consistently excellent results.

PMID- 16791063
TI  - Transfixion wire positioning within the bone: an option to control proximal tibia
      external fixation stiffness.
AB  - PURPOSE: The greatest angle that can be formed by the crossing wires at the
      proximal tibia level without altering safe corridors approaches only 60 degrees.
      Consequently, the wires are positioned more in the coronal than the sagittal
      plane. Looking for an increase in sagittal bending stiffness, we evaluated
      different wire positioning within the proximal tibia and their effect on the
      stiffness of external fixation of proximal tibia. STUDY DESIGN: A fiberglass
      composite tibia fixed into an idealized ring external frame was tested with a
      servohydraulic test frame. Load-deformation behavior was compared among the
      different wire positioning within the proximal tibia under identical conditions
      of central axial compression, medial compression-bending, posterior compression
      bending, posteromedial compression-bending, and torsion. Stiffness values were
      calculated from the load-deformation and the torque-angle curves. RESULTS: The
      sample with 3 wires positioned within the bone-2 wires crossed 1 cm posteriorly
      from the center of the tibia and the third wire placed in coronal plane 1 cm
      anteriorly from the center of the tibia-was significantly (P < 0.05) stiffer in
      posterior, posteromedial, and torsional loading configurations compared with all
      other wire positions within the bone. CONCLUSIONS: This new wire positioning
      within the proximal tibia-2 wires crossed 1 cm posteriorly from the center of the
      tibia and the third wire placed in coronal plane 1 cm anteriorly from the center
      of the tibia-increased overall stiffness of external fixation, predominantly in
      sagittal plane. CLINICAL RELEVANCE: This work provides a rationale to control
      proximal tibia external fixation stiffness in sagittal plane.

PMID- 16791064
TI  - Center of the femoral head: a magnetic resonance imaging study.
AB  - Determination of the center of the femoral head (CFH) may be difficult because of
      incomplete epiphyseal ossification of the femoral head in children younger than 8
      years. The purpose of this study is to find a practical method for determining
      the center of the femoral head in normal hips of children younger than 8 years.
      Twenty-seven children who had magnetic resonance imaging (MRI) examinations of
      their hips (N = 54) were reviewed retrospectively. The average age of the
      subjects was 4.7 years (range, 1.2-8 years). Measurements were performed on the
      closest section to the midcoronal plane of the femoral head (the widest spherical
      femoral head seen on the MRI section). The CFH on the MRI section was found using
      a constructed circular frame by using a computer program. The medial and lateral
      edges of the proximal femoral ossific nucleus were marked, and the midpoint of
      the ossific nucleus adjacent to the growth plate (MPON) was determined. The
      distance between the MPON and the CFH was calculated. The average distance was
      1.5 mm (range, 0-5 mm). The distance between these 2 points was less than or
      equal to 2 mm in 40 hips (74%). In conclusion, this study shows that the MPON can
      be used as a landmark to determine the center of the femoral head in normal hips
      of children younger than 8 years and can be used to measure the lower extremity
      mechanical axis.

PMID- 16791065
TI  - Biomechanical analysis of single screw fixation for slipped capital femoral
      epiphysis: are more threads across the physis necessary for stability?
AB  - PURPOSE: To evaluate single screw fixation stability, in the treatment of slipped
      capital femoral epiphysis, as a function of screw thread distribution across the
      physis. STUDY DESIGN: In vitro biomechanical study. METHODS: Thirty porcine
      proximal femurs were sectioned through the physeal line and stabilized with a
      cannulated 7.3-mm stainless steel AO screw. The distal 16 mm of each screw was
      threaded (5 threads). The femurs were randomized into 5 groups (1, 2, 3, 4, or 5
      threads across the physis) and biomechanically tested to determine failure load
      (N) and stiffness (N/mm). RESULTS: Femurs with 2 or 3 threads across the physis
      had a significantly greater load to failure and stiffness compared with femurs
      with 1, 4, or 5 threads across the physis (P < 0.05). CONCLUSIONS: Thread
      distribution across the physis seems to be important. When using screws with a 16
      mm thread, greatest strength and stiffness are achieved when 40%-60% of threads
      engage the epiphysis, with a significant decrease when greater than 80% of
      threads cross the physis. Too few threads in the epiphysis as well as too few in
      the metaphysis both lead to decreased stability. CLINICAL RELEVANCE: This study
      challenges the belief that compression across the physis maximizes slipped
      capital femoral epiphysis fixation stability. We recommend equal distribution of
      threads across the physis when using 16-mm thread screws, and we postulate that
      screws with a greater thread length (32 mm or fully threaded) would increase
      fixation stability even further. Optimizing purchase may decrease the incidence
      of slip progression, especially as the prevalence of obesity increases in the
      adolescent population.

PMID- 16791066
TI  - Biomechanical analysis of in situ single versus double screw fixation in a
      nonreduced slipped capital femoral epiphysis model.
AB  - Slipped capital femoral epiphyses (SCFE) were created in 24 pairs of immature
      bovine femurs. In 17 pairs of femurs, the slip was left nonreduced (one-third
      diameter of physis), and in 7 pairs, the slip was reduced. Stabilization of the
      slips was with either 1 or 2 threaded 6.5-mm screws in a compression mode. The
      specimens were subjected to shear or torsional loading forces to failure, with
      the goal of trying to reproduce clinical conditions of in situ screw fixation for
      acute or unstable SCFE. In the nonreduced model, double-screw fixation was 312%
      stiffer than single-screw fixation under torsional loading. In the reduced model,
      double-screw fixation was 137% stiffer than single-screw fixation under torsional
      loading. The increased rotational stability of double-screw fixation under
      torsional loading conditions may justify its use in in situ stabilization of
      acute or unstable SCFE.

PMID- 16791067
TI  - Surgical treatment of overgrowth of the greater trochanter in children and
      adolescents.
AB  - After developmental dislocation of the hip, Perthes disease, bacterial coxitis,
      and other pediatric hip conditions, the femoral neck may develop short, with an
      overgrowth of the greater trochanter. Forty-four patients with trochanter
      overgrowth (47 hips) ages 6 to 17 years underwent surgery. Trochanteric
      epiphysiodesis was performed in 13 patients (group A), distal transfer of the
      greater trochanter in 24 patients (26 hips; group B), and femoral neck
      lengthening osteotomy in 7 patients (8 hips; group C). The mean follow-up time
      was 8.3 years. Clinical results were evaluated by the hip score according to
      Merle d'Aubigne. Radiological parameters were evaluated by 2 of the authors. Each
      operative method led to an improvement of clinical symptoms. In group A, no
      significant changes in the radiological parameters could be found. Groups B and C
      showed significant improvements in the radiological parameters. However, no
      difference was found between these 2 groups.

PMID- 16791068
TI  - Immediate single-leg spica cast for pediatric femoral diaphysis fractures.
AB  - PURPOSE: Immediate spica cast application is the standard of care for young
      children with isolated femur fractures. We evaluated the outcomes and function of
      children treated with single-leg spica casts. METHODS: We performed a
      retrospective review of 45 children treated with single-leg spica casts.
      Demographic data, mechanism of injury, hospitalization time, time in cast, and
      complications were collected by chart review. Children returned for a physical
      examination and radiographs. Subjects completed a questionnaire about the child's
      functional level and the Activities Scale for Kids. RESULTS: There were 33 boys
      and 12 girls. The average age was 3.3 (9 months to 9 years). The mechanism of
      injury was a fall in 71%. The mean hospitalization was 1 day (0-4 days) and the
      mean time to union was 6 weeks (4-9 weeks). Ninety-five percent of the patients
      crawled in the cast, 90% pulled to stand, 81% cruised, and 62% walked either
      independently or with assistive devices. One half of the patients in school or
      daycare returned while in the cast. Two children failed because of unacceptable
      shortening. Two children required repeat reductions under anesthesia due to
      unacceptable alignment. Five casts broke at the hip joint. At final review, there
      was 1 rotational malunion. There were no radiographic malunions. The median
      Activities Scale for Kids score was 95 of 100 possible points. CONCLUSIONS: The
      single-leg spica can safely, effectively manage low-energy femur fractures in
      young children. SIGNIFICANCE: The single-leg spica may address some of the social
      concerns associated with the use of a spica cast for simple femur fractures.

PMID- 16791069
TI  - Use of flexible intramedullary nails in pediatric femur fractures.
AB  - Flexible intramedullary nails are now routinely used for stabilization of
      pediatric femur fractures. Few data are available regarding patients'
      postoperative range of motion, weight-bearing status, activity levels, use of
      immobilization, and radiographic leg length discrepancy measured via routine
      scanograms. Patients who underwent placement of flexible intramedullary nails for
      a pediatric femur fracture at a single institution from 1998 to 2003 were
      identified retrospectively. Ninety-one patients were identified with 94 femur
      fractures. The complication rate was 17% for the 94 fractures, with 8 patients
      requiring an unplanned return to surgery. The complication rate was significantly
      higher for patients aged 10 years or older (34%) as compared with that for
      younger patients (9%). Average time to full weight bearing was 10 weeks, time to
      radiographic union averaged 10.7 weeks, and time to return to preoperative level
      of activity averaged 4.9 months. Immediate postoperative weight bearing status
      was nonweight bearing in 57%. Immobilization or support was used postoperatively
      in 60% of the patients. Postoperatively, patients had minimal loss of range of
      motion in hip internal and external rotation and knee extension. Hip and knee
      flexion rapidly improved postoperatively with an average loss of hip flexion of 0
      degree by 3 months and an average loss of knee flexion of 4 degrees by 6 months.
      Postoperatively, limb length discrepancy was greater than 1 cm in 7 patients at 6
      months, 11 patients at 12 months, 3 patients at 18 months, and 2 patients at 2
      years. Two patients had persistent limb length discrepancy of greater than 2 cm,
      but only one patient required an epiphysiodesis for his limb length inequality.
      Although the end results are favorable, complications are relatively frequent,
      particularly in older children.

PMID- 16791070
TI  - Flexible intramedullary nailing in pediatric lower limb fractures.
AB  - Seventy-three children (48 boys and 25 girls; mean age, 5.7 years) with
      unilateral femoral or tibial shaft fractures were treated using elastic
      intramedullary nails at the authors' institution. There were 61 simple type A
      fractures (84%) and 12 wedge type B fractures (16%). All but 3 children had
      closed fractures. Associated injuries were seen in one third of the cases. All
      fractures were reduced by closed manipulation. Union was achieved in all cases
      without additional intervention. Technical problems occurred in few patients.
      Improper nail length was seen in 4 cases. None of the study patients developed
      deep infection. No angulation greater than 15 degrees was found after femoral
      fractures. Nine patients had length discrepancy greater than 10 mm. Spiral
      fractures showed a tendency for shortening whereas transverse fractures were more
      associated with post-traumatic lengthening. No significant axial malalignment or
      shortening was seen in tibial fractures. Torsional differences of greater than 15
      degrees were detected by computed tomography or navigated ultrasound examination
      in nearly half of the patients; however, only 4 children had clinically apparent
      gait changes. The study confirms the satisfactory results of treating pediatric
      lower limb fractures using elastic nails. Proper surgical technique and
      intraoperative control of limb alignment can help avoid postoperative
      deformities.

PMID- 16791071
TI  - Orthopaedic implants in children: survey results regarding routine removal by the
      pediatric and nonpediatric specialists.
AB  - The role of orthopaedic implant removal in children is controversial. Some
      children later require adult reconstruction; implant removal may be difficult or
      may adversely affect the outcome. The purpose of this study is to compare the
      opinions of the pediatric and nonpediatric specialists regarding routine implant
      removal in children. Participants were asked to complete a Web-based
      questionnaire containing demographics, general opinions, and a series of specific
      case scenarios related to implant removal/retention. The study group consisted of
      273 pediatric, and 99 nonpediatric specialists, with an average of 17-year
      experience. Regarding asymptomatic, stainless steel implants in children, 41%
      indicated removal most or all of the time, 36% reported sometimes, and the
      remaining 22% reported almost never or never. Implant location was the only
      important factor in the decision to remove or retain the implant. A greater
      percentage of pediatric specialists endorsed implant retention in the hip or
      pelvis in older children compared with nonpediatric specialists. More experienced
      surgeons, regardless of specialty area, recommended implant removal. Pediatric
      specialists may wish to reconsider their preference to retain large hip implants
      in older children because their nonpediatric colleagues, who presumably are faced
      with the removal from these children when they reach adulthood, recommend implant
      removal once they have served their purpose. The number of such cases and the
      role of early removal in improving the long-term outcome need further study.

PMID- 16791072
TI  - Elastic stable intramedullary nailing is the best treatment of unicameral bone
      cysts of the long bones in children?: Prospective long-term follow-up study.
AB  - Since Virchow first described the unicameral bone cyst (UBC) in 1876, several
      methods for management were proposed. Currently performed surgical procedures
      include curettage combined with bone grafting, allografting with freeze-dried
      crushed cortical bone, use of homologous cancellous bone chips, the application
      of high-porosity hydroxyapatite, and cryosurgery. Decompression with multiple
      drill holes and intralesional injections of either steroids or bone marrow have
      also been used to treat UBC, with variable success rates. Elastic stable
      intramedullary nailing for the treatment of UBC in long bones has been rapidly
      gaining popularity. Elastic stable intramedullary nailing for the treatment of a
      UBC was performed in 56 patients between 1994 and 2003. The follow-up is between
      2.1 and 11 years. Nine children were excluded because of short period of follow
      up or were lost. The study population consisted of 47 children. The cyst was
      located in the humerus in 36 patients, in the femur in 11. The mean age of the
      patients at the time of surgery was 8.9 years. Results were evaluated on plain
      radiographs according to the classification system of Capanna et al. In our study
      population of 47 UBCs, 31 (65.9 %) were classified as completely healed, and 16
      (34.1%) were healed with residual radiolucency. No recurrence or no response was
      observed. Each lesion responded to treatment after the nailing. This method can
      solve in time the pathology, and we feel that, with skilled hands, this method is
      the best one for UBC treatment in the long bones of the children.

PMID- 16791073
TI  - Dynamic lower extremity alignment in children with achondroplasia.
AB  - The purpose of this study is to analyze lower extremity dynamic malalignment
      during gait using a 3-dimensional kinematics and kinetics in 13 children (3-17
      years old) with achondroplasia and to compare measurements of alignment and
      malrotation between gait, radiographic, and clinical measures. Gait analysis in
      the coronal plane showed a varus malalignment of the knee (19 +/- 13 degrees) and
      variable tibial torsion abnormalities (13 [internal] +/- 15.7 degrees).
      Radiographs also showed knee varus malalignment (16 +/- 9 degrees); however,
      there was poor correlation with gait analysis measures (P > 0.05). In the
      sagittal plane, radiographs showed genu recurvatum deformity (23.5 +/- 13.2
      degrees), although the sagittal plane knee kinematics were normal. Kinetic
      analyses of the knee showed high internal knee valgus moments (external varus
      moments, 0.48 +/- 0.25 N m/kg), which were significantly different from the
      normal population (P < 0.05). In conclusion, there is a 3-dimensional, complex,
      dynamic deformity of the lower extremity present in children with achondroplasia.
      We recommend a very careful assessment of the limb focusing on both the static
      and dynamic varus deformity and tibial torsion using a combination of
      radiographic, clinical, and gait analysis.

PMID- 16791074
TI  - Transient meralgia paresthetica after pediatric posterior spine fusion.
AB  - Meralgia paresthetica (MP) rarely occurs during posterior spine surgery. The
      study goal was to examine risk factors associated with the incidence of MP. A
      review of 56 consecutive pediatric patients undergoing posterior spine fusion for
      scoliosis was performed. Patients with abnormal sensation in the lateral thigh
      preoperatively and prior spine surgery were excluded. All patients were
      positioned prone on the Jackson (Orthopaedic Systems, Inc., Union City, CA)
      spinal table with either (1) the lower leg support table and thigh supports or
      (2) the lower leg suspension sling. Data on patient weight, diagnosis, surgeon,
      duration of surgery, presence of MP, symptoms, and symptom duration were
      collected. A logistic regression analysis was performed between independent
      variables and presence of MP. There were 10/56 patients with MP (18%). Symptoms
      were anterolateral thigh numbness without pain or weakness. Symptoms in all cases
      were resolved, on average, before the 6-week postoperative visit (range 2-24
      weeks). Patients with MP more often had idiopathic scoliosis (28% vs 7%; P <
      0.05) were positioned with the lower leg sling instead of the flat table support
      (31% vs 13%; P < 0.05) and trended toward longer surgery times (451 vs 388
      minutes; NS). Abnormal body mass index, age at surgery, surgeon, and sex did not
      correlate to MP. MP can occur after pediatric posterior spine surgery. Symptoms
      were minor, temporary, and did not require treatment. Shorter surgical times and
      use of thigh pads in conjunction with the lower leg support table may decrease
      the incidence of MP.

PMID- 16791075
TI  - Comparison of the complication rates between first and second (repeated)
      lengthening in the same limb segment.
AB  - The purpose of this study is to compare the incidence and types of complications
      in children who are undergoing first and second (repeated) lengthenings of the
      same bone. This is a retrospective review of 11 children (12 limbs) who underwent
      limb lengthenings of the same bone twice. There were 7 femoral and 5 tibial
      repeated lengthenings. Diagnoses included congenital femoral deficiency or
      proximal femoral focal deficiency in 6 patients, fibular hemimelia in 2,
      achondroplasia in 2, and tibial hypoplasia in 1. Mean age was 8.5 years for the
      first lengthening and 11.5 years for the second lengthening. There were 2.2
      complications per lengthening for the first procedure and 1.5 for the second
      lengthening. There were 5 major and 22 minor complications for the first
      lengthening and 1 major and 17 minor complications for the second lengthening,
      none of these data were found to be statistically different. The healing index
      was 1.3 +/- 0.43 months per cm first lengthening and 2.2 +/- 1.7 cm for the
      second lengthening. This study did not demonstrate a significantly higher rate of
      complications with repeated lengthening of the same limb, although the time in
      the fixator for the second lengthening was longer and the degree of lengthening
      less.

PMID- 16791076
TI  - Factors associated with internal hip rotation gait in patients with cerebral
      palsy.
AB  - Internal rotation gait is common in children with cerebral palsy. Factors thought
      to contribute include femoral anteversion, hip flexor tightness, imbalance of hip
      rotators, and hamstring and adductor tightness. The exact cause of internal
      rotation must be defined before contemplating surgery. We investigated the
      prevalence of internal hip rotation and associated factors, which are considered
      to influence this walking pattern, in patients with cerebral palsy. Gait
      laboratory data of 222 patients with cerebral palsy were studied retrospectively.
      Two groups were selected; those with maximum dynamic hip internal rotation of
      more than 27 degrees and those with less than 20 degrees. Of 222 patients, 27.0%
      (diplegia, 61.7%; hemiplegia, 38.3%) had at least one hip with dynamic internal
      rotation of more than 27 degrees. This study suggests that dynamic hip internal
      rotation is multifactorial in origin. The most significant differences in
      clinical measures were found in values of passive hip external rotation range,
      femoral anteversion and hip flexor contracture. We discuss the role of early
      treatment of hip flexion contracture.

PMID- 16791077
TI  - A prospective evaluation of the WeeFIM in patients with cerebral palsy undergoing
      orthopaedic surgery.
AB  - PURPOSE: Although frequently used in pediatric rehabilitation settings, the
      WeeFIM has not been tested in surgical pediatric orthopaedic patients. METHODS:
      The WeeFIM was administered to patients with surgical cerebral palsy at defined
      intervals preoperatively and at both 6 and 12 months postoperatively. The age
      adjusted change scores from baseline to follow-up were tested both parametrically
      and nonparametrically. RESULTS: Four hundred sixty-eight patients had baseline
      evaluations. There were 161 six-month follow-up assessments and 108 twelve-month
      follow-up assessments. The baseline WeeFIM was able to separate children with
      different patterns of cerebral palsy. Hemiplegic patients had higher scores than
      diplegic and tetraplegic patients. Overall age-adjusted scores were improved at
      both 6 (mean increase 2.0) and 12 months (mean increase 2.2). The instrument
      showed significant ceiling effects for diplegic and hemiplegic patients with
      lower or upper extremity surgery and limited responsiveness for lower extremity
      surgery in tetraplegic patients. Parametrically, it showed improvements in
      mobility for both rhizotomy and tetraplegic upper extremity surgery.
      Nonparametric tests were not significant for rhizotomy mobility improvement.
      CONCLUSIONS: Although the WeeFIM adequately reflects the severity of neurological
      involvement in pediatric orthopaedic patients with cerebral palsy, it has a
      significant ceiling effect in diplegic and hemiplegic patients limiting
      responsiveness and lacks content validity for tetraplegic patients. The
      instrument may have some use in tetraplegic patients with upper extremity surgery
      and in rhizotomy patients. We recommend against its general use for orthopaedic
      surgery in patients with cerebral palsy lower extremity or spine surgery and in
      hemiplegic patients with upper extremity surgery.

PMID- 16791078
TI  - Unilateral versus bilateral peri-ilial pelvic osteotomies combined with proximal
      femoral osteotomies in children with cerebral palsy: perioperative complications.
AB  - The purpose of this study is to evaluate if bilateral peri-ilial pelvic
      osteotomies (PIPO) combined with proximal femoral varus derotation osteotomies
      (VDRO) influenced postoperative complications in children with spastic
      quadriplegia. Bilateral and unilateral hip subluxation or dislocation secondary
      to spasticity was present in 29 and 61 patients, respectively. The children were
      divided into 2 groups: group 1 were to be performed a surgery for unilateral PIPO
      associated with bilateral VDRO, and group 2 were to be performed a surgery for
      bilateral PIPO and VDRO. The average age of patients at initiation of surgery was
      11.7 years (range, 5-20 years) for group 1 and 10.7 years (range, 5-19 years) for
      group 2. The hospital stay was similar for group 1 and 2 (P = 0.797), which was 9
      days. In group 1, 11 (18%) of 61 children needed an average of 2 days (range, 1-7
      days) in the intensive care unit postoperatively, and 4 of these 11 patients were
      reintubated because of respiratory problems. In group 2, 6 (20%) of 29 children
      were transferred to the intensive care unit postoperatively for an average of 2
      days (range, 1-4 days) and 3 of these 6 children were reintubated because of
      respiratory problems. In conclusion, respiratory problems and anemia were the
      most common early postoperative complications, which occur with a similar rate in
      children with spastic quadriplegia who underwent bilateral or unilateral peri
      ilial pelvic osteotomy(ies) combined with proximal femoral osteotomies. We
      believe that bilateral hip procedures including PIPO, proximal femoral
      osteotomies, and soft-tissue release can be performed safely in 1 stage and,
      based on this data, the staged procedure would probably have the same risk as the
      first procedure.

PMID- 16791079
TI  - Heterotopic ossification following hip osteotomies in cerebral palsy: incidence
      and risk factors.
AB  - The aims of this study are, first, to determine the incidence of heterotopic
      ossification (HO) in patients with cerebral palsy (CP) who have undergone pelvic
      and/or proximal femoral osteotomies and, second, to identify any risk factors
      that may contribute to its development in this patient population. The
      radiographs of 219 consecutive patients with CP who underwent proximal femoral
      osteotomies with or without pelvic osteotomies were reviewed. Risk factors
      including gender, age, and degree of involvement, ambulatory status, previous hip
      operations, bilateral hip surgery, capsular release, concomitant pelvic
      osteotomy, infection, and history of exuberant callus were evaluated. Thirty-five
      (16%) patients were diagnosed with HO and the 5 factors that cause HO were
      identified, which are degree of involvement (quadriplegic), ambulatory status,
      capsular release, infection, and previous hip operations. Based on logistic
      regression analysis, if a patient had quadriplegic type of CP, then they have
      17.5 times more risk for HO than a patient with hemiplegic type, and capsular
      release increases the risk 237 times. Although HO occurred in 16% of patients
      treated with bony procedures in the hip, in a small group (2%) of children it had
      a clinically significant limitation requiring surgical resection. In this study,
      clear risk factors were presented for the development of HO; however, none of
      these risk factors can be altered in ways that will reduce the risk for HO. These
      risk factors might be used to define a high-risk group in whom attempts at
      prophylactic treatment for prevention of HO could be initiated.

PMID- 16791080
TI  - Quantitative gait analysis in the treatment of children with cerebral palsy.

PMID- 16791081
TI  - Idiopathic.

PMID- 16791082
TI  - CADASIL-causing mutations do not alter Notch3 receptor processing and activation.
AB  - CADASIL is associated with mutations in the Notch3 gene but the causal mechanisms
      of the disorder remain unclear. We studied effects of widely established
      mutations on Notch3 receptor processing and ligand-mediated activation in stable
      lines of HEK293 and SH-SY5Y cells expressing either human wild-type or mutant
      Notch3 receptor. None of the four mutations (R90C, R133C, C185R and R449C)
      affected quantities of the full-length, amino-terminal or carboxyl-terminal
      fragments and did not impair intracellular trafficking in both cell types. The
      Jagged 1, Jagged 2 and Delta ligand-mediated S2 site cleavage and signal
      transduction were also observed to be similar in both wild-type and mutants,
      which exhibited similar rates of degradation of full-length, amino-terminal and
      carboxyl-terminal fragments. Our results suggest that the arteriopathy in CADASIL
      is caused by other mechanisms not necessarily involving Notch3 processing and
      activation.

PMID- 16791083
TI  - Regional network of magnetic resonance imaging gray matter volume in healthy
      aging.
AB  - Healthy aging has been associated with brain volume reductions preferentially
      affecting the frontal cortex, but also involving other regions. We used a network
      model of regional covariance, the Scaled Subprofile Model, with magnetic
      resonance imaging voxel-based morphometry to identify the regional distribution
      of gray matter associated with aging in 26 healthy adults, 22-77 years old.
      Scaled Subprofile Model analysis identified a pattern that was highly correlated
      with age (R2=0.66, P<or=0.0001). Older age was associated with less gray matter
      in the bilateral frontal, temporal,thalamic, and right cerebellar regions. Gender
      differences suggested more advanced brain aging in the men. In this healthy adult
      sample, aging was associated with a regional pattern of gray matter atrophy most
      prominently involving the frontal and temporal cortices. Scaled Subprofile Model
      network analysis may aid in the detection and tracking of brain aging and in the
      evaluation of putative antiaging therapies.

PMID- 16791085
TI  - A nonparametric quantification of neural response field structures.
AB  - The response fields of higher cortical neurons are usually approximated with
      smooth mathematical functions for the purpose of population parameterization or
      theoretical modeling. We used instead two nonparametric methods (principal
      component analysis and independent component analysis), which provided a basis
      for the response field clustering. Although both methods performed
      satisfactorily, the principal component analysis space is more straightforward to
      calculate. It also gave a clear preference toward the smallest number of
      functional response field classes. Clustering was performed with both K-means and
      superparamagnetic clustering algorithms with similar results. We also show that
      the shapes of the eigenvectors remain consistent regardless of the response field
      data sets size. This finding reflects the fact that the response fields were
      generated by the same neural network and encode the same underlying process.

PMID- 16791084
TI  - Infant speech perception activates Broca's area: a developmental
      magnetoencephalography study.
AB  - Discriminative responses to tones, harmonics, and syllables in the left
      hemisphere were measured with magnetoencephalography in neonates, 6-month-old
      infants, and 12-month-old infants using the oddball paradigm. Real-time head
      position tracking, signal space separation, and head position standardization
      were applied to secure quality data for source localization. Minimum current
      estimates were calculated to characterize infants' cortical activities for
      detecting sound changes. The activation patterns observed in the superior
      temporal and inferior frontal regions provide initial evidence for the
      developmental emergence early in life of a perceptual-motor link for speech
      perception that may depend on experience.

PMID- 16791086
TI  - Nitric oxide synthase inhibitor attenuates number of regenerating spinal
      motoneurons in adult rats.
AB  - Neuronal survival and death-related effects of nitric oxide synthase are widely
      studied, yet its potential involvement in regeneration remains largely
      unexplored. In the present study, the regenerative role of nitric oxide synthase
      in injured motoneurons was investigated. A ventral root was avulsed and a piece
      of peripheral nerve was implanted into the spinal cord. Results showed that
      nitric oxide synthase inhibitor reduced the number of regenerating motoneurons to
      half compared with sham-operated control at 2 weeks and 4 weeks after injury, but
      the rate of axonal regeneration was not affected. Our study adds a new line of
      evidence that expression of nitric oxide synthase is beneficial to the axonal
      regeneration of the injured spinal motoneurons.

PMID- 16791087
TI  - Rapid and efficient differentiation of dopaminergic neurons from mouse embryonic
      stem cells.
AB  - We have developed a fast and effective method for the differentiation of
      dopaminergic neurons from mouse embryonic stem cells. Neuronal precursors are
      obtained by formation of embryonic bodies or neural stem spheres via free
      floating culture in the presence of the mitogens basic fibroblast growth factor
      and epidermal growth factor together with L-ascorbic acid. Subsequent culturing
      of the precursor cells in medium containing epidermal growth factor, FGF8b, SHH
      and ascorbic acid induces cell proliferation, following withdrawal of the growth
      factors leads differentiation into predominantly dopaminergic neurons. Mature
      neurons are obtained within 10 days of replacing the proliferation to
      differentiation medium. Embryonic stem-derived dopaminergic neurons are purified
      by cell sorting and may serve as a convenient source for the study of molecular,
      genetic and cellular properties of dopaminergic neurons.

PMID- 16791088
TI  - Neural differentiation of embryonic stem cells induced by conditioned medium from
      neural stem cell.
AB  - Embryonic stem cells can proliferate indefinitely and are capable of
      differentiating into derivatives of all three embryonic germ layers in vitro,
      including the neural lineage. The main objective of this study is to test the
      effects of neural stem cell conditioned medium on the neural differentiation of
      mouse embryonic stem cells. When cultured in neural stem cell conditioned medium,
      mouse embryonic stem cells can form floating cell spheres composed of many nestin
      positive cells. After trypsinization and growth on gelatin, these embryonic stem
      cell-derived neural progenitor cells can be expanded for more than 3 months
      without loss of neural progenitor characteristics. Both neuronal and glial cells
      can be readily generated from these cells under differentiation conditions. Thus,
      neural stem cell conditioned medium is a highly potent reagent for inducing the
      development of mouse embryonic stem cells into the neural lineage, especially
      neural progenitor cells.

PMID- 16791089
TI  - Can stroke patients walk after complete lateral corticospinal tract injury of the
      affected hemisphere?
AB  - The lateral corticospinal tract is the major motor pathway in humans. The role of
      this tract on walking, however, is uncertain. The development of diffusion tensor
      tractography enables corticospinal tract status to be visualized at the
      subcortical level. In the present study, we undertook to demonstrate that some
      stroke patients can walk despite complete lateral corticospinal tract injury. Ten
      stroke patients who were able to walk with evidence of complete unilateral
      lateral corticospinal tract injury, as determined by clinical course, brain
      magnetic resonance imaging, and diffusion tensor tractography, were recruited. We
      conclude that some stroke patients can walk despite complete lateral
      corticospinal tract injury of the affected hemisphere.

PMID- 16791090
TI  - Numerical distance effect in the N240 component in a number-matching task.
AB  - The event-related potential technique was used to investigate the time course and
      scalp-potential topography for the numerical distance effect in a number-matching
      task. Twenty undergraduates judged whether a number matched or did not match
      another number presented 1.5 s earlier. Compared with number pairs with a 'small'
      numerical distance (distance=1), number pairs with a 'large' numerical distance
      (greater than 2) showed a longer latency and a greater positive amplitude in the
      N240 component. This numerical distance effect was limited to fronto-central
      electrodes. These results were discussed in terms of the neural bases of the
      numerical distance effect during the automatic processing of numbers.

PMID- 16791091
TI  - Understanding of physiological neural firing patterns through dynamical
      bifurcation machineries.
AB  - The characteristics of baroreceptor firing patterns were recognized in
      experiment, and their dynamics revealed in theoretical analysis. During blood
      pressure elevation, baroreceptors gradually exhibited bursting, continuous
      firing, and paradoxical bursting patterns. The bursting was generated through the
      repeated bifurcations between rest and spiking, the continuous firing was
      maintained without bifurcation, and the paradoxical bursting was generated
      through the bifurcations between spiking and a depolarization block. Thus, the
      change of blood pressure spans two bifurcations and such results imply a new way
      for baroreceptors to encode blood pressure information. Various firing patterns
      were generated from the evolution of the baroreceptor system on different parts
      of the system's bifurcation scenario with respect to parameter I, the excitative
      current modulated by blood pressure.

PMID- 16791092
TI  - Are you ready? I can tell by looking at your microsaccades.
AB  - The direction of microsaccades has been shown to be biased by the allocation of
      spatial attention. Here, we investigated whether the cognitive processes involved
      in preparing to respond to an upcoming target can modulate the microsaccadic
      response. Specifically, we found that optimal manual response preparation,
      reflected by faster response times, was associated with a reduction in the
      absolute frequency of microsaccades. The present results are consistent with
      previous studies suggesting a relationship between oculomotor activity and
      different sorts of motor responses. Our findings, however, surprisingly
      demonstrate that the effect of preparation and stimulus expectation extends to an
      automatic and unconscious oculomotor activity such as microsaccade execution.

PMID- 16791093
TI  - Cortical activation during memory-guided saccades.
AB  - Using functional magnetic resonance imaging, we compared responses during
      visually guided saccades with those evoked during memory-guided saccades, in
      which participants executed saccades to remembered locations. Eye movements were
      recorded in the magnetic resonance tomograph. Significantly stronger activation
      during memory-guided saccades was observed in the posterior portion of the right
      inferior frontal gyrus, in the left inferior frontal eye field, in the posterior
      parietal cortex, as well as in the right posterior superior temporal gyrus. The
      posterior part of the dorsal anterior cingulum and a small voxel cluster in the
      dorsolateral prefrontal area, anterior to the left inferior frontal eye field,
      were only active in the memory-guided condition.

PMID- 16791094
TI  - Is there a mismatch negativity during change blindness?
AB  - The mismatch negativity is an event-related potential that represents a
      preattentive change detection process. The aim of this study was to determine
      whether the mismatch negativity was present during 'change blindness', a striking
      phenomenon in which surprisingly large changes in a complex scene are not seen
      when they occur during a blink or an eye movement. In this study, large
      orientation changes elicited a candidate mismatch negativity between 180 and 320
      ms that appeared to be independent of participants' performance (uncued 76%
      correct, miscued 59% correct with chance performance at 50%). This negativity,
      however, disappeared in the miscued 'change blind' condition. In conclusion, the
      mismatch negativity does not appear to be present during change blindness
      suggesting that in complex scenes even large changes may not trigger preattentive
      change detection processes.

PMID- 16791095
TI  - Syntactic event-related potential components in 24-month-olds' sentence
      comprehension.
AB  - The processing of syntactic violations in adults is associated with a biphasic
      event-related potential pattern consisting of an early left anterior negativity
      and a late positivity called the P600. While the early left anterior negativity
      reflects highly automatic sentence parsing, the P600 reflects processes of
      syntactic reanalyses or repair. The present study investigated the processing of
      phrase structure information in 24-month-old German-speaking children. During the
      experimental session, the children listened to short active sentences that were
      either syntactically correct or contained a phrase structure violation. The event
      related potential s of the children displayed a late positivity in response to
      phrase structure violations. Our findings indicate that even children at this
      early age are sensitive to syntactic errors in the form of phrase structure
      violations.

PMID- 16791096
TI  - Vagal complex monocarboxylate transporter-2 expression during hypoglycemia.
AB  - Astrocytic provision of lactate provision to neurons may be a critical indicator
      of substrate fuel availability in metabolic sensing sites in the brain, including
      the hindbrain dorsal vagal complex. We examined the hypothesis that vagal complex
      monocarboxylate transporter protein levels are gender dependent and estrogen
      dependent, and that estrogen influences adaptation of these protein responses
      during repeated insulin-induced hypoglycemia. Western blot analyses showed that
      male and estrogen-treated ovariectomized female rats exhibit opposite changes in
      monocarboxylate transporter-2 levels after one insulin injection, as well as
      divergent patterns of adaptation to this metabolic challenge. The data suggest
      that sex differences in hypoglycemic patterns in vagal complex lactate transport
      may underlie disparate signaling of cellular energy imbalance.

PMID- 16791097
TI  - Speech apraxia without oral apraxia: can normal brain function explain the
      physiopathology?
AB  - Apraxia of speech, usually associated with stroke, refers to the inability to
      perform speech motor movements typically with an intact ability to execute non
      speech oral movements. It is uncertain whether apraxia of speech results from
      damage affecting the insula or the inferior frontal gyrus. The controversy
      started because of conflicting results from studies investigating patients with
      disrupted brain structure, when dysfunction of both sites can coexist. We
      conducted a functional magnetic resonance imaging study of individuals without
      neurological disorders comparing speech and non-speech movements. Speech
      movements did not recruit the insula, but activated the left inferior frontal
      gyrus, suggesting that Broca's area, but not the insula, is critical for speech
      articulation.

PMID- 16791098
TI  - Abnormal neural activity in children with attention deficit hyperactivity
      disorder: a resting-state functional magnetic resonance imaging study.
AB  - In this study, a newly reported regional homogeneity approach was used to analyze
      blood oxygen level-dependent functional magnetic resonance imaging data on
      resting state in boys with attention deficit hyperactivity disorder. Boys with
      attention deficit hyperactivity disorder showed decreased regional homogeneity in
      the frontal-striatal-cerebellar circuits, but increased regional homogeneity
      mainly in the occipital cortex. Our findings are consistent with the hypothesis
      of abnormal frontal-striatal-cerebellar circuits in attention deficit
      hyperactivity disorder. The regional homogeneity approach may be a potentially
      useful method in exploring the pathophysiology of attention deficit hyperactivity
      disorder.

PMID- 16791099
TI  - Modulation of prefrontal cortex activation by emotional words in recognition
      memory.
AB  - We employed event-related functional magnetic resonance imaging to examine
      emotional valence effects on verbal recognition memory. Using a yes/no
      recognition task, we focussed on prefrontal cortex responses to positive,
      negative and neutral words. Behavioral data confirmed enhanced processing of
      emotional items and functional magnetic resonance imaging revealed different
      subregions in the prefrontal cortex supporting retrieval of emotional words.
      Activations in the right mid-ventrolateral prefrontal cortex correlated with the
      correct retrieval conditions for negative words, whereas the right ventromedial
      and orbitofrontal prefrontal cortex showed enhanced responses to positive words.
      Additionally, differences between old and new items mainly affected bilateral
      orbitofrontal regions when processing positive words. The results are discussed
      in terms of higher monitoring demands owing to familiarity-based recognition bias
      for emotional words.

PMID- 16791100
TI  - Phonetic mismatch negativity predicts verbal memory deficits in schizophrenia.
AB  - Deficits in auditory sensory memory at the electrophysiological level as indexed
      by mismatch negativity and those in auditory verbal memory at the
      neuropsychological level have been independently demonstrated in previous studies
      of schizophrenia. We predicted a specific association between these indices in
      schizophrenia. Mismatch negativities elicited by change in tone duration and
      phoneme duration were recorded in 23 schizophrenia patients, who were also
      evaluated for auditory verbal memory and executive function. Lower amplitude of
      mismatch negativity under the phoneme-duration condition was significantly
      associated with worse verbal memory. Phoneme-duration mismatch negativity was not
      correlated with executive function, nor was tone-duration mismatch negativity
      correlated with verbal memory. These results suggest that electrophysiological
      auditory sensory memory dysfunction underlies the basis for neuropsychological
      auditory verbal memory deficits in schizophrenia.

PMID- 16791102
TI  - Impaired duration mismatch negativity in developmental dyslexia.
AB  - A mismatch negativity event-related potential protocol was administered to
      dyslexic children and their respective controls to test whether a specific
      auditory deficit concerning phonetic processing or a lower level auditory
      processing deficit was present in developmental dyslexia. Three different
      contrast conditions were explored, including nonphonological sounds, contrasted
      in pitch and duration, and phonemes. Mismatch negativity amplitudes differed
      significantly between groups in the duration condition, whereas no differences
      were found in the frequency and phoneme conditions. Moreover, the dyslexic
      children had delayed mismatch negativity latencies in the three contrast
      conditions. Our results suggest a deficit in low-level auditory discrimination in
      dyslexic children, in particular when detecting stimulus duration, and support
      the rapid auditory processing theory of dyslexia.

PMID- 16791101
TI  - Testing for causality with transcranial direct current stimulation: pitch memory
      and the left supramarginal gyrus.
AB  - Neuroimaging studies have implicated the left supramarginal gyrus in short-term
      auditory memory processing, including memory for pitch. The present study
      investigated the causal role of the left supramarginal gyrus in short-term pitch
      memory by comparing the effects of cathodal transcranial direct current
      stimulation when applied over the left or right supramarginal gyrus with sham
      transcranial direct current stimulation. Only cathodal transcranial direct
      current stimulation over the left supramarginal gyrus had a detrimental effect on
      short-term pitch-memory performance in 11 adult participants. These results
      provide support for the important role of the left supramarginal gyrus in short
      term memory for pitch information, and they further demonstrate the potential of
      transcranial direct current stimulation to modulate the functional contribution
      of a brain area to a particular cognitive process.

PMID- 16791103
TI  - Using semantic memory to boost 'episodic' recall in a case of developmental
      amnesia.
AB  - We report two experiments that investigated factors that might boost 'episodic'
      recall for Jon, a developmental amnesic whose episodic memory is gravely impaired
      but whose semantic memory seems relatively normal. Experiment 1 showed that Jon's
      recall improved following a semantic study task compared with a non-semantic
      study task, as well as following four repeated study trials compared with only
      one. Experiment 2 additionally revealed that Jon's recall improved after acting
      compared with reading action phrases at study, but only if the phrases were well
      integrated semantically. The results provide some support for the hypothesis that
      Jon's 'episodic' recall depends on the extent to which he is able to retrieve
      events using semantic memory.

PMID- 16791104
TI  - Orthographic neighborhood effects in reading Chinese two-character words.
AB  - The present study investigates the effects of neighborhood size and neighborhood
      frequency in reading Chinese two-character words. The neighborhood size of a word
      is defined as the summation of neighbors sharing the first constituent
      (neighborhood size 1) and the second constituent (neighborhood size 2)
      characters. The first experiment found two opposite neighborhood size effects in
      lexical decision of high-frequency and low-frequency words. The regression
      analysis showed that neighborhood size 1 influenced word reading more than the
      neighborhood size 2. The second experiment confirmed this finding and showed that
      reading words with higher frequency neighbors took a longer time and elicited
      greater N400 and LPC than those without higher frequency neighbors. These
      findings indicate that, when reading Chinese two-character words, all words
      sharing the first constituent character are activated in the early stage of word
      recognition and the existence of high-frequency words among neighbors leads to
      greater competition in the stage of semantic integration and response selection.

PMID- 16791105
TI  - Family-based association study between G72/G30 genetic polymorphism and
      schizophrenia.
AB  - Genetic variations in G72/G30 have been reported to be associated with
      schizophrenia and bipolar disorders in several case-control studies. This gene is
      located in a genomic region known to contain susceptibility genes for
      schizophrenia. As case-control studies carry an increased risk of confounding
      through population stratification, we investigate whether the rs947267 (A/C)
      polymorphism is associated with schizophrenia in a family-based association
      study. This polymorphism is located within the G72/G30 gene and has been
      previously associated with bipolar disorders. The sample consisted of a total of
      216 Chinese families that included an affected offspring and parents.
      Transmission disequilibrium analysis revealed a significant association between
      the G72/G30 rs947267 polymorphism and schizophrenia (P=0.016), with the A allele
      more commonly transmitted to patients. Further analysis stratified by sex showed
      that the A allele was significantly more overtransmitted than nontransmitted in
      the trios of male probands (P=0.031), but not in the trios of female probands.
      Our family-based association study supports the suggestion that the G72/G30 gene
      may be implicated in susceptibility to schizophrenia and there may be an
      interaction between this gene and sex in the pathogenesis of schizophrenia.

PMID- 16791106
TI  - Stability of substantia nigra pars reticulata neuronal discharge rates during
      dopamine receptor blockade and its possible mechanisms.
AB  - It is hypothesized that substantia nigra pars reticulata neurons become
      overactive during a deficit of dopamine transmission. In this study, we examined
      how acute dopamine receptor blockade (SCH23390 and eticlopride) affects impulse
      activity of substantia nigra pars reticulata neurons and their response to
      iontophoretic gamma-amino-n-butyric acid in awake, unrestrained rats. No changes
      in discharge rate were found during complete dopamine receptor blockade, but
      these neurons showed a diminished response to gamma-amino-n-butyric acid,
      suggesting gamma-amino-n-butyric acid receptor hyposensitivity. This may result
      from tonic increase in gamma-amino-n-butyric acid input from the striatum and
      globus pallidus, which are activated during dopamine receptor blockade. As
      substantia nigra pars reticulata neurons are autoactive and resistant to tonic
      increases in gamma-amino-n-butyric acid input, changes in their responsiveness to
      phasic gamma-amino-n-butyric acid inputs, not tonic increase discharge rate, may
      underlie movement disturbance following dopamine deficit.

PMID- 16791107
TI  - Prenatal stress reduces S100B in the neonatal rat hippocampus.
AB  - Prenatal stress has been shown to disturb neonatal rat brain development. The
      astroglial-specific neurotrophic factor S100B is known to play an important role
      in normal brain development. In the present study, we investigated the effects of
      prenatal stress on S100B concentrations in the hippocampus of 1-day-old Fischer
      344 rats. Overall, prenatal stress resulted in a 25% reduction in hippocampal
      S100B content. Further, male hippocampal S100B content was negatively correlated
      with plasma corticosterone levels. Positive correlations were found between
      female S100B levels and fetal growth, and hippocampal brain-derived neurotrophic
      factor content. In conclusion, the observed reduction in neonatal hippocampal
      S100B levels, as a consequence of prenatal stress, may be involved in affecting
      postnatal brain development.

PMID- 16791108
TI  - Influence of negative expiratory pressure ventilation on hemodynamic variables
      during severe hemorrhagic shock.
AB  - OBJECTIVE: Outcome after trauma with severe hemorrhagic shock is still dismal.
      Since the majority of blood is present in the venous vessels, it might be
      beneficial to perform venous recruiting via the airway during severe hemorrhagic
      shock. Therefore, the purpose of our study was to evaluate the effects of
      negative expiratory pressure ventilation on mean arterial blood pressure, cardiac
      output, and short-term survival during severe hemorrhagic shock. DESIGN:
      Prospective study in 21 laboratory animals. SETTING: University hospital research
      laboratory. SUBJECTS: : Tyrolean domestic pigs. INTERVENTIONS: After induction of
      controlled hemorrhagic shock (blood loss approximately 45 mL/kg), 21 pigs were
      randomly ventilated with either zero end-expiratory pressure (0 PEEP; n = 7), 5
      cm H2O positive end-expiratory pressure (5 PEEP; n = 7), or negative expiratory
      pressure ventilation (up to -30 cm H2O at the endotracheal tube during
      expiration; n = 7). MEASUREMENTS AND MAIN RESULTS: Mean (+/-sd) arterial blood
      pressure was significantly higher in the negative expiratory pressure ventilation
      swine when compared with the 0 PEEP (38 +/- 5 vs. 27 +/- 3 mm Hg; p = .001) and
      the 5 PEEP animals (38 +/- 5 vs. 20 +/- 6 mm Hg; p < .001) after 5 mins of the
      experiment. Cardiac output was significantly higher in the negative expiratory
      pressure ventilation swine when compared with the 0 PEEP (3.1 +/- .4 vs. 1.9 +/-
      .9 L/min; p = .001) and 5 PEEP animals (3.1 +/- .4 vs. 1.2 +/- .8 L/min; p <
      .001) after 5 mins of the experiment. All seven negative expiratory pressure
      ventilation animals, but only three of seven 0 PEEP animals (p = .022), survived
      the 120-min study period, whereas all seven of seven 5 PEEP animals were dead
      within 35 mins (p < .001). Limitations include that blood loss was controlled and
      that the small sample size limits the evaluation of survival outcome.
      CONCLUSIONS: When compared with pigs ventilated with either 0 PEEP or 5 PEEP,
      negative expiratory pressure ventilation during severe hemorrhagic shock improved
      mean arterial blood pressure and cardiac output.

PMID- 16791109
TI  - Effects of levosimendan on right ventricular afterload in patients with acute
      respiratory distress syndrome: a pilot study.
AB  - OBJECTIVE: Acute respiratory distress syndrome (ARDS) is frequently associated
      with increased pulmonary vascular resistance and thus with systolic load of the
      right ventricle. We hypothesized that levosimendan, a new calcium sensitizer with
      potential pulmonary vasodilator properties, improves hemodynamics by unloading
      the right ventricle in patients with ARDS. DESIGN: Prospective, randomized,
      placebo-controlled, pilot study. SETTING: Twenty-two-bed multidisciplinary
      intensive care unit of a university hospital. PATIENTS: Thirty-five patients with
      ARDS in association with septic shock. INTERVENTIONS: Patients were randomly
      allocated to receive a 24-hr infusion of either levosimendan 0.2 microg/kg/min (n
      = 18) or placebo (n = 17). Data from right heart catheterization, cardiac
      magnetic resonance, arterial and mixed venous oxygen tensions and saturations,
      and carbon dioxide tensions were obtained before and 24 hrs after drug infusion.
      MEASUREMENTS AND MAIN RESULTS: At a mean arterial pressure between 70 and 80 mm
      Hg (sustained with norepinephrine infusion), levosimendan increased cardiac index
      (from 3.8 +/- 1.1 to 4.2 +/- 1.0 L/min/m) and decreased mean pulmonary artery
      pressure (from 29 +/- 3 to 25 +/- 3 mm Hg) and pulmonary vascular resistance
      index (from 290 +/- 77 to 213 +/- 50 dynes/s/cm(5)/m(2); each p < .05).
      Levosimendan also decreased right ventricular end-systolic volume and increased
      right ventricular ejection fraction (p < .05). In addition, levosimendan
      increased mixed venous oxygen saturation (from 63 +/- 8 to 70 +/- 8%; p < .01).
      CONCLUSIONS: This study provides evidence that levosimendan improves right
      ventricular performance through pulmonary vasodilator effects in septic patients
      with ARDS. A large multiple-center trial is needed to investigate whether
      levosimendan is able to improve the overall prognosis of patients with sepsis and
      ARDS.

PMID- 16791110
TI  - Carbamoyl phosphate synthase-1: a marker of mitochondrial damage and depletion in
      the liver during sepsis.
AB  - OBJECTIVE: Mitochondrial damage and dysfunction are thought to play an important
      role in the pathogenesis of sepsis-induced organ failures. Unfortunately,
      specific markers of mitochondrial damage in vital organs do not currently exist.
      Recently, carbomyl phosphate synthase (CPS)-1, a protein primarily localized to
      liver mitochondria, was found to be present in high concentrations in the plasma
      of septic humans. Thus, we hypothesized that the circulatory release of CPS-1
      would correlate with mitochondrial damage or impaired mitochondrial function in
      the liver in a clinically relevant model of sepsis. DESIGN: Prospective,
      randomized, controlled animal study. SETTING: University medical center research
      laboratory. SUBJECTS: Male, Balb/C mice, aged 10-12 wks. INTERVENTIONS: Animals
      were assigned to receive cecal ligation and puncture (CLP sepsis) or sham
      operation and compared with untreated controls. Plasma CPS-1 levels and liver
      mitochondrial variables, including morphology, respiratory activity, mass (i.e.,
      cardiolipin content), and protein carbonylation, were assessed at various time
      points (8, 24, and 48 hrs and 6 days) after surgery. MEASUREMENTS AND MAIN
      RESULTS: Oxidant stress (i.e., carbonylation) was detected within 8 hrs of CLP
      and persisted through 48 hrs. Plasma CPS-1 levels increased dramatically at 24
      hrs, remained significantly elevated at 48 hrs, and normalized by 6 days in the
      sepsis group. Abnormalities of liver mitochondrial morphology and function
      coincided with increased plasma CPS-1 levels. Mitochondrial depletion in the
      liver was not due to cell death but was associated with increased lysosomal
      clearance. Increased expression of mitochondrial biogenesis factors preceded
      restoration of mitochondrial variables and normalization of CPS-1 levels by day
      6. CONCLUSIONS: Circulating CPS-1 is a marker of mitochondrial damage and
      depletion in the liver during the subacute phase of CLP sepsis. From a
      mechanistic standpoint, mitochondrial depletion is not due to cell death but is
      apparently related to the removal of damaged mitochondria by lysosomes (i.e.,
      autophagy), followed by repletion of mitochondrial populations. Further studies
      are needed to determine the clinical utility of CPS-1 as a marker of sepsis
      severity.

PMID- 16791111
TI  - Improving medical student intensive care unit communication skills: a novel
      educational initiative using standardized family members.
AB  - OBJECTIVE: To determine whether intensive care unit (ICU) communication skills of
      fourth-year medical students could be improved by an educational intervention
      using a standardized family member. DESIGN: Prospective study conducted from
      August 2003 to May 2004. SETTING: Tertiary care university teaching hospital.
      PARTICIPANTS: All fourth-year students were eligible to participate during their
      mandatory four-week critical care medicine clerkship. INTERVENTIONS: The
      educational intervention focused on the initial meeting with the family member of
      an ICU patient and included formal teaching of a communication framework followed
      by a practice session with an actor playing the role of a standardized family
      member of a fictional patient. At the beginning of the critical care medicine
      rotation, the intervention group received the educational session, whereas
      students in the control group did not. MEASUREMENTS AND MAIN RESULTS: At the end
      of each critical care medicine rotation, all students interacted with a different
      standardized family member portraying a different fictional scenario. Sessions
      were videotaped and were scored by an investigator blinded to treatment
      assignment using a standardized grading tool across four domains: a)
      introduction; b) gathering information; c) imparting information; and d) setting
      goals and expectations. A total of 106 (97% of eligible) medical students agreed
      to participate in the study. The total mean score as well as the scores for the
      gathering information, imparting information, setting goals, and expectations
      domains for the intervention group were significantly higher than for the control
      group (p < .01). CONCLUSIONS: The communication skills of fourth-year medical
      students can be improved by teaching and then practicing a framework for an
      initial ICU communication episode with a standardized family member.

PMID- 16791112
TI  - Survival of propofol infusion syndrome in a head-injured patient.
AB  - OBJECTIVE: To describe the clinical progression of an adult patient with
      traumatic brain injury who survived propofol infusion syndrome. DESIGN: Case
      report. SETTING: Tertiary care surgical intensive care unit. PATIENT: A 21-yr-old
      male with traumatic brain injury was administered high doses of propofol for
      sedation and intracranial pressure control combined with vasopressor therapy to
      maintain cerebral perfusion pressure >60 mmHg. He developed a significant
      metabolic acidosis with a lactic acid level of 10.9 mmol/L. INTERVENTIONS:
      Exploratory laparotomy, discontinuation of propofol infusion. MEASUREMENTS AND
      MAIN RESULTS: An exploratory abdominal laparotomy was negative for traumatic
      injury. During the procedure, the propofol infusion was considered a possible
      cause and was discontinued. On review, it became apparent that a combination of
      high-dose propofol and catecholamines were responsible for the lactic acidosis.
      An echocardiogram revealed severe left ventricular dysfunction and
      cardiomyopathy, which resolved within 19 days. CONCLUSIONS: High-dose propofol
      should be avoided and alternative agents should be instituted for sedation and
      intracranial pressure management. The use of catecholamine infusions to maintain
      cerebral perfusion pressure in the setting of a high-dose propofol infusion may
      be pharmacologically unsound and may be a triggering factor for propofol infusion
      syndrome. Identification of the syndrome and discontinuation of propofol resulted
      in complete reversal of symptoms in the case described.

PMID- 16791113
TI  - Nitric oxide involvement in the hemodynamic response to fluid resuscitation in
      endotoxic shock in rats.
AB  - OBJECTIVE: Fluid loading is an essential part of cardiovascular resuscitation in
      septic shock. We hypothesized that fluid administration increases blood flow
      velocity and thus endothelial shear stress, causing the release of nitric oxide
      by the vascular endothelium. Because of endothelial dysfunction in sepsis, this
      mechanism would be less effective in septic animals. Fluid loading may have
      different effects in septic compared with control animals. DESIGN: Prospective,
      randomized, controlled study. SETTING: Animal research laboratory. SUBJECTS: Male
      Sprague-Dawley rats. INTERVENTIONS: We tested the involvement of nitric oxide in
      the fluid-induced cardiovascular response after administration of
      lipopolysaccharide (5 mg/kg, n = 10) or vehicle (control, n = 10) in rats
      subsequently randomized after 165 mins to receive L-N(G)-nitroarginine (7.5
      mg/kg) or saline (n = 5 in each group). At 180 mins, all animals received
      hydroxyethyl starch (fluid loading, 15 mL/kg in 15 mins). Reversal of L-N(G)
      nitroarginine was studied with an intravenous bolus of L-arginine (300 mg/kg).
      MEASUREMENTS AND MAIN RESULTS: Lipopolysaccharide injection induced a hypokinetic
      shock (low blood pressure: -30% +/- 9%, p < .05), low cardiac output (aortic
      pulsed-Doppler probe: -20% +/- 8, p < .05), and unchanged systemic conductance,
      which turned into a hyperkinetic shock by fluid loading. Pretreatment with L-N(G)
      nitroarginine totally abolished this fluid loading-induced vasodilation in
      control rats but only partially in lipopolysaccharide-treated rats, suggesting an
      altered endothelial response after lipopolysaccharide injection. Maximal aortic
      blood flow acceleration was used as an index of left ventricular systolic
      function. The improvement of maximal aortic blood flow acceleration observed
      during fluid loading in lipopolysaccharide-treated or control animals was blunted
      by L-N(G)-nitroarginine pretreatment, suggesting the involvement of nitric oxide
      in the myocardial response to fluid loading. CONCLUSIONS: These results suggest
      that the endothelium participates in the hemodynamic response to fluid loading in
      control rats, but less in rats with septic shock, secondary to an altered nitric
      oxide-dependent vasodilation.

PMID- 16791114
TI  - Amphibian peptides prevent endotoxemia and bacterial translocation in bile duct
      ligated rats.
AB  - OBJECTIVE: To investigate the efficacy of amphibian antimicrobial peptides in
      preventing bacterial translocation and neutralizing endotoxins in bile duct
      ligated rats. DESIGN: Prospective, randomized, controlled animal study. SETTING:
      Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats.
      INTERVENTIONS: Adult male Wistar rats underwent sham operation or bile duct
      ligation (BDL). Eight groups were studied: sham operation with saline treatment,
      sham operation with 120 mg/kg tazobactam-piperacillin, sham operation with 2
      mg/kg uperin 3.6, sham operation with 2 mg/kg magainin2, BDL with saline
      treatment, BDL with 120 mg/kg tazobactam-piperacillin, BDL with 2 mg/kg uperin
      3.6, and BDL with 2 mg/kg magainin2. MEASUREMENTS AND MAIN RESULTS: Main outcome
      measures were: endotoxin and tumor necrosis factor-alpha concentrations in plasma
      and evidence of bacterial translocation in blood, peritoneum, liver, and
      mesenteric lymph nodes. Endotoxin and tumor necrosis factor-alpha plasma levels
      were significantly higher in BDL rats compared with sham-operated animals. All
      amphibian peptides achieved a significant reduction of plasma endotoxin and tumor
      necrosis factor-alpha concentration when compared with saline- and tazobactam
      piperacillin-treated groups. On the other hand, both tazobactam-piperacillin and
      peptides significantly reduced bacterial growth compared with the control.
      Tazobactam-piperacillin and magainin2 exerted the maximal inhibition of bacterial
      growth. CONCLUSION: In conclusion, because of their multifunctional properties,
      amphibian peptides could be interesting compounds to inhibit bacterial
      translocation and endotoxin release in obstructive jaundice.

PMID- 16791115
TI  - Pharmacogenetic characteristics of indinavir, zidovudine, and lamivudine therapy
      in HIV-infected adults: a pilot study.
AB  - OBJECTIVE: The aim of the study was to investigate relationships among indinavir,
      lamivudine-triphosphate, and zidovudine-triphosphate pharmacokinetics and
      pharmacodynamics with polymorphisms in CYP3A5, MDR1, MRP2, MRP4, BCRP, and UGT1A1
      genes. STUDY DESIGN: Retrospective pilot investigation among 33 subjects who
      participated in a randomized pharmacological study of indinavir, lamivudine, and
      zidovudine. Subjects were defined as genetic variant carriers or not.
      Relationships were investigated with multivariable regression. Indinavir
      clearance was adjusted for African American race; triphosphates for sex; and HIV
      response for study arm, drug exposure, and baseline HIV-RNA. RESULTS: Genetically
      determined CYP3A5 expressors had 44% faster indinavir oral clearance versus
      nonexpressors (P = 0.002). MRP2-24C/T variant carriers had 24% faster indinavir
      oral clearance (P = 0.05). Lamivudine-triphosphate concentrations were elevated
      20% in MRP4 T4131G variant carriers (P = 0.004). A trend for elevated zidovudine
      triphosphates was observed in MRP4 G3724A variant carriers (P = 0.06). The log10
      changes in HIV-RNA from baseline to week 52 were -3.7 for MDR1 2677 TT, -3.2 for
      GT, and -2.2 for GG (P < 0.05). Bilirubin increases were 2-fold higher in UGT1A1
      [TA]7/[TA]7 genotypes. No relationships were identified with BCRP. DISCUSSION:
      Novel relationships were identified among genetic variants in drug transporters
      and indinavir, lamivudine-triphosphate, and zidovudine-triphosphate
      concentrations. CYP3A5 expression was associated with faster indinavir oral
      clearance. These pilot data provide a scientific basis for more rational
      utilization of antiretroviral drugs.

PMID- 16791116
TI  - Oxidant stress and peripheral neuropathy during antiretroviral therapy: an AIDS
      clinical trials group study.
AB  - BACKGROUND: Peripheral neuropathy that complicates HIV nucleoside reverse
      transcriptase inhibitor (NRTI) therapy is likely caused by mitochondrial injury.
      Mitochondria play a central role in regulating oxidant stress. We explored the
      relationships between oxidant stress and NRTI-induced peripheral neuropathy.
      METHODS: The AIDS Clinical Trials Group (ACTG) studied the cases of 384
      antiretroviral-naive individuals randomized to receive didanosine/stavudine or
      zidovudine/lamivudine, plus efavirenz, nelfinavir, or both. The participants were
      followed for up to 3 years. Peripheral neuropathy was ascertained by signs and
      symptoms. We performed a case-control study of ACTG 384 participants. Peripheral
      neuropathy cases and nonneuropathy control subjects were selected from
      didanosine/stavudine recipients. Alternate control subjects were selected from
      zidovudine/lamivudine recipients who developed peripheral neuropathy. Oxidant
      stress was assessed by quantifying F2-isoprostanes (F2-IsoPs) in cryopreserved
      plasma. RESULTS: Seventy-five cases, 71 control subjects, and 18 alternate
      control subjects were identified. The median baseline F2-IsoP values were 53
      (interquartile range [IQR], 40-85), 57 (IQR, 41-77), and 53 (IQR, 47-101) pg/mL,
      respectively, and did not differ between cases and control subjects (P = 0.78) or
      alternate control subjects (P = 0.60). Changes in F2-IsoPs from baseline to time
      of peripheral neuropathy did not differ significantly between cases (median, 10
      [IQR, -17 to 26] pg/mL) and control subjects (median, 4 [IQR, -11 to 17] pg/mL; P
      = 0.48) or alternate control subjects (median, 1 [IQR, -48 to 10] pg/mL; P =
      0.21). CONCLUSIONS: Peripheral neuropathy that complicates antiretroviral therapy
      with NRTIs was not associated with increased systemic oxidant stress assessed by
      plasma F2-IsoPs.

PMID- 16791117
TI  - Human herpesvirus 8 oral shedding in HIV-infected men with and without Kaposi
      sarcoma.
AB  - OBJECTIVES: Two main routes of human herpesvirus 8 (HHV-8) transmission are
      known: sexual, predominantly in men who have sex with men; and nonsexual, in
      endemic populations. Both routes implicate saliva, so identifying the factors
      that influence oral HHV-8 shedding is important. METHODS: Using polymerase chain
      reaction and immunohistochemistry, we prospectively analyzed HHV-8 infection of
      oral epithelial cells in 98 Swiss HIV Cohort Study patients, with mean follow-up
      of 9.4 years, and correlated data to immune status, HHV-8 serology, and Kaposi
      sarcoma (KS) history, as well as survival. RESULTS: Sixty-eight (43.9%) of the 98
      men were HHV-8 seropositive, and 33 (33.67%) had a history of KS. In both groups,
      men who have sex with men were significantly more affected than heterosexuals (P
      < 0.05). Of 77 patients, 9 (11.6%) were oral HHV-8 polymerase chain reaction
      positive, and 2 of these were also positive by immunohistochemistry. Oral HHV-8
      detection was not influenced by the immune status, but a trend toward higher
      detection was observed in patients with KS (P = 0.084). Oral HHV-8 shedding had
      no predictive value either for the development of KS lesions or for survival.
      CONCLUSIONS: Human herpesvirus 8 can be present in oral epithelial cells and is
      shed independent of the patient's immune status, indicating that oral HHV-8
      shedding may occur at any time in HHV-8-seropositive individuals.

PMID- 16791118
TI  - The correlation between prevalence of oral manifestations of HIV and CD4+
      lymphocyte counts weakens with time.

PMID- 16791120
TI  - [Serrated neoplasia of the gastro-intestinal tract].
AB  - Serrated neoplasia of the gastro-intestinal tract have peculiar microscopic and
      molecular features that are still incompletely described. Some serrated polyps
      seem to be involved in a new carcinogenic pathway in the colon: the serrated
      neoplasia pathway, with hypermethylation of the cytosine-guanine dinucleotides,
      located in the promoter of some genes such as h-MLH1, BRAF and MGMT. The natural
      history of the serrated polyps and their risk for progression to malignancy are
      still unclear. There is no official guideline for the management of serrated
      polyps. The aim of this article is to describe the epidemiological,
      morphological, immunohistochemical and molecular characteristics of the serrated
      neoplasia of the gastrointestinal tract: hyperplastic polyps, "traditional"
      serrated adenomas, mixed hyperplastic and adenomatous polyps, sessile serrated
      adenomas, hyperplastic polyposis and serrated adenocarcinomas.

PMID- 16791121
TI  - [Soft tissue non lymphoid malignant round cell tumors in childhood and
      adolescence: morphological, immunophenotypic, and molecular features of
      diagnosis].
AB  - Soft tissue non lymphoid malignant round cell tumors observed in children and
      adolescents are rare and are very different from adult tumors. They are often
      undifferentiated and distinctive key morphologic features are often lacking, but,
      on the other hand, specific recurrent genetic alterations, mostly translocations,
      are distinctive. Immunohistochemical features are also important for the
      diagnosis, and there is sometimes a strong correlation between the presence or
      the absence of an immunoreactivity for a specific protein and the presence of a
      specific genetic alteration. Finally, careful morphologic histological
      examination and immunohistochemical features will lead to a diagnosis which will
      be often confirmed by cytogenetics (translocations) or molecular techniques
      (fusion transcripts, deletion, mutation).

PMID- 16791122
TI  - [Peritoneal serous borderline tumors: report of two cases].
AB  - Two cases of serous borderline tumors of the peritoneum are reported. These rare
      tumors may show variable histological features. The lack of peritoneal invasion,
      which may be difficult to assess, with minimal or no ovarian involvement are
      major features for the diagnosis. These tumors should be distinguished from other
      peritoneal neoplasms such as serous carcinomas because of their good prognosis
      after surgical therapy alone.

PMID- 16791123
TI  - [Complexity of pathological interpretation in megacystis-microcolon-intestinal
      hypoperistalsis syndrome].
AB  - Megacystis-microcolon-intestinal hypoperistalsis syndrome is very rare, and is
      the most severe of the chronic intestinal pseudoobstructions. Diagnosis is
      usually made in the neonatal period, is clinical and radiological, and is
      confirmed by manometric studies. Microscopic abnormalities are variable,
      inconstant and nonspecific. They involve the smooth muscle more often than the
      intrinsic innervation of the gut and the bladder. A girl, currently seven years
      old, presented with megacystis observed on prenatal ultrasound at 21 weeks of
      gestation. At first, amniotic fluid volume was appropriate for gestational age,
      and then hydramnios appeared at 30 weeks of gestation. Microcolon was discovered
      at birth, with microileum, dilatation of the duodenum and proximal jejunum,
      intestinal malposition, and severe hypoperistalsis of the entire gastrointestinal
      tract, which indicated enterostomy and total parenteral nutrition from birth. At
      pathological examination, rectal biopsy and enteric nervous plexuses were normal.
      There was hypoplasia of the external longitudinal layer of the muscularis propria
      in the colon and ileum. Cajal cells could not be demonstrated
      immunohistochemically in the colon. This case highlights the complexity and
      difficulties of pathological interpretation in this syndrome, and the necessity
      of a large study of controls at different ages and different levels of the
      digestive tract and the bladder.

PMID- 16791124
TI  - [Malignant rhabdoid tumor of the liver with spontaneous rupture: a case report].
AB  - We report the case of an 8-year-old child, presenting a rhabdoid tumor of the
      liver with spontaneous rupture, revealed by an intra-abdominal bleeding with
      rapidly fatal course. This clinical and pathological report raises the problem of
      the differential diagnosis of primary malignant hepatic tumors of the child with
      no alpha-foetoprotein increase.

PMID- 16791125
TI  - [An unusual and misleading form of pilocytic astrocytoma].
AB  - Pilocytic astrocytoma is histologically characterized by a biphasic pattern. We
      report a myxoid form of frontocallosal pilocytic astrocytoma in a 13-year-old
      girl. MRI showed a relatively well-defined tumor with necrosis and ring-like zone
      of contrast enhancement. Histological examination showed a monophasic tumor
      composed of piloid cells on a myxoid background corresponding to a pilomyxoid
      astrocytoma. This unusual form of pilocytic astrocytoma can be mistaken for a
      high grade infiltrating glioma. Pilomyxoid astrocytoma is more aggressive than
      classic pilocytic astrocytoma and has to be distinguished from it.

PMID- 16791126
TI  - [A polypoid lesion of the chin].

PMID- 16791127
TI  - [An unusual thyroid].

PMID- 16791128
TI  - [A palpebral tumor].

PMID- 16791129
TI  - [Tumor of the tongue in a child].

PMID- 16791130
TI  - [A rare pigmented tumor of soft tissues].

PMID- 16791131
TI  - [A cutaneous nodule of the neckline].

PMID- 16791132
TI  - [Contribution of post mortem diagnosis of HIV infection in Cameroon].

PMID- 16791133
TI  - Rapid HIV test distribution--United States, 2003-2005.
AB  - At the end of 2003, an estimated 1 million persons in the United States were
      living with human immunodeficiency virus (HIV) infection, including those with
      acquired immunodeficiency syndrome (AIDS); approximately one fourth of these
      persons had not had their infections diagnosed. In 2003, CDC implemented a new
      initiative, Advancing HIV Prevention (AHP), focused, in part, on reducing the
      prevalence of undiagnosed HIV infection by expanding HIV testing and taking
      advantage of rapid HIV tests that enable persons to receive results within 30
      minutes, instead of the 2 weeks typically associated with conventional tests. In
      support of AHP strategies, during September 2003-December 2005, CDC purchased and
      distributed rapid HIV tests to expand testing and assess the feasibility of using
      rapid tests in new environments (e.g., outreach settings or emergency
      departments). This report summarizes the results of this rapid HIV-test
      distribution program (RTDP), in which CDC distributed tests to 230 organizations
      in the United States and identified 4,650 (1.2%) HIV infections among 372,960
      rapid tests administered. The results suggest that RTDP helped scale up rapid HIV
      testing programs in the United States and enabled diagnosis of HIV in persons who
      might not have had their infections diagnosed otherwise.

PMID- 16791134
TI  - Methicillin-resistant Staphylococcus aureus skin infections among tattoo
      recipients--Ohio, Kentucky, and Vermont, 2004-2005.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      infections have emerged as a major cause of skin disease in the United States.
      Outbreaks of CA-MRSA have occurred among athletes, inmates at correctional
      facilities, and military recruits. This report summarizes investigations of six
      unlinked clusters of skin and soft tissue infections caused by CA-MRSA among 44
      recipients of tattoos from 13 unlicensed tattooists in three states (Ohio,
      Kentucky, and Vermont); use of nonsterile equipment and suboptimal infection
      control practices were identified as potential causes of the infections.
      Clinicians should consider CA-MRSA in their differential diagnosis for
      staphylococcus diseases, including skin infections. Clinicians can contact their
      local health departments to determine the prevalence of CA-MRSA in their
      community and whether the disease is reportable. MRSA infections should be added
      to education and prevention campaigns highlighting the risks of unlicensed
      tattooing.

PMID- 16791135
TI  - Progress toward poliomyelitis eradication--Pakistan and Afghanistan, January 2005
      May 2006.
AB  - As of March 2006, wild poliovirus (WPV) remained indigenous in four countries:
      Afghanistan, India, Nigeria, and Pakistan. Since 2005, WPV-endemic countries in
      Asia have intensified their polio eradication measures through use of type 1
      monovalent oral polio vaccine (mOPV1) and implementation of innovative social
      mobilization, communication, and vaccine-delivery strategies. This report
      describes polio eradication strategies in Afghanistan and Pakistan during January
      2005-May 2006.

PMID- 16791138
TI  - DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case
      control studies.
AB  - The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected
      candidate gene for cancer susceptibility. However, association studies on the
      XRCC3 polymorphisms (4541A>G, Thr(241)Met, 17893A>G) in cancer have shown
      conflicting results. Therefore, we performed a meta-analysis to better assess the
      purported associations. Forty eight eligible case-control studies including
      24,975 cancer patients and 34, 209 controls were selected for our meta-analysis.
      Overall, individuals carrying the XRCC3 Met/Met genotype showed a small cancer
      risk under a recessive genetic model. The subgroup and meta-regression analysis
      demonstrated different scenarios concerning the XRCC3 Met/Met genotype's role in
      cancer susceptibility for different subgroups. Specially, there was a
      significantly increased risk of breast cancer (OR, 1.14; P=0.0004; 95% CI, 1.06
      1.23; P=0.37 for heterogeneity), elevated but not significant risk of cancer for
      head and neck, bladder, surprisingly, a significantly decreased risk of non
      melanoma skin cancer (OR, 0.76; P=0.007; 95% CI, 0.62-0.93; P=0.61 for
      heterogeneity). A significantly elevated risk of cancer was observed in
      population-based case-control studies but not in nested or hospital based
      studies. Similarly, we found a significantly increased risk of cancer for A4541G
      and a decreased risk for A17893G under dominant genetic models. Our meta-analysis
      results support that the XRCC3 might represent a low-penetrance susceptible gene
      especially for cancer of breast, bladder, head and neck, and non-melanoma skin
      cancer. A single larger study should be required to further evaluate gene-gene
      and gene-environment interactions on XRCC3 polymorphisms and tissue-specific
      cancer risk in an ethnicity specific population.

PMID- 16791139
TI  - Association study of the G-protein signaling 4 (RGS4) and proline dehydrogenase
      (PRODH) genes with schizophrenia: a meta-analysis.
AB  - Schizophrenia is a devastating psychiatric disease that affects up to 1% of the
      population worldwide. Recent studies suggested that schizophrenia might result
      from the hypofunction of glutamatergic neurotransmission. Systematic positional,
      expression and functional studies have implicated the regulator of G-protein
      signaling 4 (RGS4) and proline dehydrogenase (PRODH) genes as promising and novel
      candidates for explaining schizophrenia. However, the findings of association
      studies tend to vary depending on the different populations on which they have
      been conducted. To reconcile this conflict of evidence, we combined all available
      population-based and family-based studies up to July 2005 involving eight
      polymorphisms. However, this meta-analysis did not find statistically significant
      evidence for association between the two glutamate-related genes and
      schizophrenia on the basis of either allelic or genotypic analysis. This may be
      the first systematic meta-analysis study based on RGS4 and PRODH.

PMID- 16791136
TI  - On the structure of the stator of the mitochondrial ATP synthase.
AB  - The structure of most of the peripheral stalk, or stator, of the F-ATPase from
      bovine mitochondria, determined at 2.8 A resolution, contains residues 79-183, 3
      123 and 5-70 of subunits b, d and F6, respectively. It consists of a continuous
      curved alpha-helix about 160 A long in the single b-subunit, augmented by the
      predominantly alpha-helical d- and F6-subunits. The structure occupies most of
      the peripheral stalk in a low-resolution structure of the F-ATPase. The long
      helix in subunit b extends from near to the top of the F1 domain to the surface
      of the membrane domain, and it probably continues unbroken across the membrane.
      Its uppermost region interacts with the oligomycin sensitivity conferral protein,
      bound to the N-terminal region of one alpha-subunit in the F1 domain. Various
      features suggest that the peripheral stalk is probably rigid rather than
      resembling a flexible rope. It remains unclear whether the transient storage of
      energy required by the rotary mechanism takes place in the central stalk or in
      the peripheral stalk or in both domains.

PMID- 16791140
TI  - Association of a 31 bp VNTR in the CBS gene with postload homocysteine
      concentrations in the Framingham Offspring Study.
AB  - Elevated total plasma homocysteine concentrations (tHcy), both fasting and post
      methionine load, have been established as risk factors for vascular disease.
      Recently, we described the association of a 31 bp variable number of tandem
      repeats (VNTR) in the cystathionine beta-synthase (CBS) gene with both CBS enzyme
      activity and tHcy concentrations. In the present study, we determined the 31 bp
      VNTR genotypes in 2598 individuals of the Framingham Offspring Study and studied
      the association between this genotype and fasting, 2-h post-methionine load and
      delta (ie increase upon methionine loading) tHcy concentrations in 1416 subjects.
      We observed a positive association between the number of repeat units of the CBS
      31 bp VNTR and both postload and delta tHcy concentrations. Adjustment for
      possible effect modifying factors like age, sex and vitamin (B6, B12 and folate)
      status did not change this observation. We hereby confirm the results of our
      earlier study, in which we found that this 31 bp VNTR is a genetic determinant of
      post-methionine load tHcy concentrations. Since also post-methionine load tHcy
      concentrations are found to be associated with an increased risk for
      cardiovascular disease (CVD), this 31 bp VNTR may be considered a risk factor for
      CVD.

PMID- 16791141
TI  - The primate cortico-cerebellar system: anatomy and function.
AB  - Evidence has been accumulating that the primate cerebellum contributes not only
      to motor control, but also to higher 'cognitive' function. However, there is no
      consensus about how the cerebellum processes such information. The answer to this
      puzzle can be found in the nature of cerebellar connections to areas of the
      cerebral cortex (particularly the prefrontal cortex) and in the uniformity of its
      intrinsic cellular organization, which implies uniformity in information
      processing regardless of the area of origin in the cerebral cortex. With this in
      mind, the relatively well-developed models of how the cerebellum processes
      information from the motor cortex might be extended to explain how it could also
      process information from the prefrontal cortex.

PMID- 16791142
TI  - Decoding mental states from brain activity in humans.
AB  - Recent advances in human neuroimaging have shown that it is possible to
      accurately decode a person's conscious experience based only on non-invasive
      measurements of their brain activity. Such 'brain reading' has mostly been
      studied in the domain of visual perception, where it helps reveal the way in
      which individual experiences are encoded in the human brain. The same approach
      can also be extended to other types of mental state, such as covert attitudes and
      lie detection. Such applications raise important ethical issues concerning the
      privacy of personal thought.

PMID- 16791143
TI  - The neurobiology of itch.
AB  - The neurobiology of itch, which is formally known as pruritus, and its
      interaction with pain have been illustrated by the complexity of specific
      mediators, itch-related neuronal pathways and the central processing of itch.
      Scratch-induced pain can abolish itch, and analgesic opioids can generate itch,
      which indicates an antagonistic interaction. However, recent data suggest that
      there is a broad overlap between pain- and itch-related peripheral mediators
      and/or receptors, and there are astonishingly similar mechanisms of neuronal
      sensitization in the PNS and the CNS. The antagonistic interaction between pain
      and itch is already exploited in pruritus therapy, and current research
      concentrates on the identification of common targets for future analgesic and
      antipruritic therapy.

PMID- 16791144
TI  - The distribution and targeting of neuronal voltage-gated ion channels.
AB  - Voltage-gated ion channels have to be at the right place in the right number to
      endow individual neurons with their specific character. Their biophysical
      properties together with their spatial distribution define the signalling
      characteristics of a neuron. Improper channel localization could cause
      communication defects in a neuronal network. This review covers recent studies of
      mechanisms for targeting voltage-gated ion channels to axons and dendrites,
      including trafficking, retention and endocytosis pathways for the preferential
      localization of particular ion channels. We also discuss how the spatial
      localization of these channels might contribute to the electrical excitability of
      neurons, and consider the need for future work in this emerging field.

PMID- 16791145
TI  - Variability, compensation and homeostasis in neuron and network function.
AB  - Neurons in most animals live a very long time relative to the half-lives of all
      of the proteins that govern excitability and synaptic transmission. Consequently,
      homeostatic mechanisms are necessary to ensure stable neuronal and network
      function over an animal's lifetime. To understand how these homeostatic
      mechanisms might function, it is crucial to understand how tightly regulated
      synaptic and intrinsic properties must be for adequate network performance, and
      the extent to which compensatory mechanisms allow for multiple solutions to the
      production of similar behaviour. Here, we use examples from theoretical and
      experimental studies of invertebrates and vertebrates to explore several issues
      relevant to understanding the precision of tuning of synaptic and intrinsic
      currents for the operation of functional neuronal circuits.

PMID- 16791146
TI  - A clustered plasticity model of long-term memory engrams.
AB  - Long-term memory and its putative synaptic correlates the late phases of both
      long-term potentiation and long-term depression require enhanced protein
      synthesis. On the basis of recent data on translation-dependent synaptic
      plasticity and on the supralinear effect of activation of nearby synapses on
      action potential generation, we propose a model for the formation of long-term
      memory engrams at the single neuron level. In this model, which we call clustered
      plasticity, local translational enhancement, along with synaptic tagging and
      capture, facilitates the formation of long-term memory engrams through
      bidirectional synaptic weight changes among synapses within a dendritic branch.

PMID- 16791147
TI  - Gene-environment interactions in psychiatry: joining forces with neuroscience.
AB  - Gene-environment interaction research in psychiatry is new, and is a natural ally
      of neuroscience. Mental disorders have known environmental causes, but there is
      heterogeneity in the response to each causal factor, which gene-environment
      findings attribute to genetic differences at the DNA sequence level. Such
      findings come from epidemiology, an ideal branch of science for showing that a
      gene-environment interactions exist in nature and affect a significant fraction
      of disease cases. The complementary discipline of epidemiology, experimental
      neuroscience, fuels gene-environment hypotheses and investigates underlying
      neural mechanisms. This article discusses opportunities and challenges in the
      collaboration between psychiatry, epidemiology and neuroscience in studying gene
      environment interactions.

PMID- 16791148
TI  - Sleep behaviour: activity and sleep in dolphins.
AB  - According to Lyamin and co-authors, neonate bottlenose dolphins (Tursiops
      truncatus) almost never sleep, unlike all other mammals that have been studied.
      Although we agree that young dolphins never stop and float at the surface, we
      find that they spend a considerable amount of time asleep while swimming. Our
      findings therefore call into question the conclusions of Lyamin et al..

PMID- 16791150
TI  - Sleep behaviour: sleep in continuously active dolphins.
AB  - Sleep has been assumed to be necessary for development and to be a vital function
      in mammals and other animals. However, Lyamin et al. claim that in bottlenose
      dolphins (Tursiops truncatus) and killer whales (Orcinus orca), neonates and
      their mothers show almost no sleep behaviour for the first month after birth;
      this conclusion is based on their observation that the cetaceans keep swimming,
      avoid obstacles and rarely close their eyes for 24 hours a day throughout that
      period. Here we analyse the behaviour and eye closure of three neonate-mother
      pairs of bottlenose dolphins and find that, although the animals tend to open
      both eyes when surfacing to breathe, one or both eyes are closed during 'swim
      rest', an underwater sleeping behaviour that is associated with continuous
      activity. This observation calls into question the conclusions of Lyamin et al.,
      who overlooked this type of sleep by analysing the animals' eye state only when
      they surfaced to breathe.

PMID- 16791154
TI  - Urgent but balanced.

PMID- 16791155
TI  - Neuroethics needed.

PMID- 16791156
TI  - The mad technologist.

PMID- 16791158
TI  - Doomsday food store takes pole position.

PMID- 16791159
TI  - Tissue-sample payments anger lawmakers.

PMID- 16791161
TI  - Open-access journal hits rocky times.

PMID- 16791162
TI  - Congress pushes plan to make papers free.

PMID- 16791163
TI  - Plan to rank universities fails to impress.

PMID- 16791164
TI  - Lure of lie detectors spooks ethicists.

PMID- 16791167
TI  - Science in the movies: from microscope to multiplex--an MRI scanner darkly.

PMID- 16791168
TI  - Science in the movies: from microscope to multiplex--betrayal at the bench.

PMID- 16791169
TI  - Conservation biology: the tiger's retreat.

PMID- 16791170
TI  - Angling saxons.

PMID- 16791171
TI  - Education and training put Iran ahead of richer states.

PMID- 16791172
TI  - Misconduct: Chinese funding body unmoved.

PMID- 16791173
TI  - Misconduct: exposure is not like Cultural Revolution.

PMID- 16791174
TI  - Misconduct: lack of action provokes web accusations.

PMID- 16791179
TI  - Animal behaviour: trust in fish.

PMID- 16791180
TI  - Astrophysics: magnetic accretion.

PMID- 16791181
TI  - Cell biology: the Golgi grows up.

PMID- 16791182
TI  - Plant biology: designs on Rubisco.

PMID- 16791183
TI  - Materials science: relaxors go critical.

PMID- 16791184
TI  - Immunology: a second chance for the thymus.

PMID- 16791185
TI  - Pollination: self-fertilization strategy in an orchid.
AB  - Mating in flowering plants normally relies on animals, wind, gravity or secretion
      to convey pollen grains from the male (anther) to the female (stigma) organ. Here
      we describe a new type of self-pollination mechanism in the tree-living orchid
      Holcoglossum amesianum, in which the bisexual flower turns its anther against
      gravity through 360 degrees in order to insert pollen into its own stigma cavity 
      without the aid of any pollinating agent or medium. This mode of self
      pollination, which occurs under windless, drought conditions when insects are
      scarce, adds to the variety of mechanisms that have evolved in angiosperms to
      ensure their reproductive success.

PMID- 16791186
TI  - Photonics: lasers producing tailored beams.
AB  - Compact lasers that can produce a range of beam patterns are important for
      progress in several areas, including the improvement of optical tweezers, ultra
      high-density optical memory and microfluidics. Here we engineer photonic crystals
      to generate semiconductor lasers that produce a range of beam patterns while
      maintaining stable single-mode oscillation. Our results could contribute to the
      realization of compact lasers that are capable of producing diverse beam patterns
      on demand.

PMID- 16791187
TI  - Genetic mechanisms and evolutionary significance of natural variation in
      Arabidopsis.
AB  - Genomic studies of natural variation in model organisms provide a bridge between
      molecular analyses of gene function and evolutionary investigations of adaptation
      and natural selection. In the model plant species Arabidopsis thaliana, recent
      studies of natural variation have led to the identification of genes underlying
      ecologically important complex traits, and provided new insights about the
      processes of genome evolution, geographic population structure, and the selective
      mechanisms shaping complex trait variation in natural populations. These advances
      illustrate the potential for a new synthesis to elucidate mechanisms for the
      adaptive evolution of complex traits from nucleotide sequences to real-world
      environments.

PMID- 16791188
TI  - The magnetic nature of disk accretion onto black holes.
AB  - Although disk accretion onto compact objects-white dwarfs, neutron stars and
      black holes-is central to much of high-energy astrophysics, the mechanisms that
      enable this process have remained observationally difficult to determine.
      Accretion disks must transfer angular momentum in order for matter to travel
      radially inward onto the compact object. Internal viscosity from magnetic
      processes and disk winds can both in principle transfer angular momentum, but
      hitherto we lacked evidence that either occurs. Here we report that an X-ray
      absorbing wind discovered in an observation of the stellar-mass black hole binary
      GRO J1655 - 40 (ref. 6) must be powered by a magnetic process that can also drive
      accretion through the disk. Detailed spectral analysis and modelling of the wind
      shows that it can only be powered by pressure generated by magnetic viscosity
      internal to the disk or magnetocentrifugal forces. This result demonstrates that
      disk accretion onto black holes is a fundamentally magnetic process.

PMID- 16791189
TI  - The giant electromechanical response in ferroelectric relaxors as a critical
      phenomenon.
AB  - The direct conversion of electrical energy to mechanical work by a material is
      relevant to a number of applications. This is illustrated by ferroelectric
      'relaxors' such as Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) (PMN-PT; refs 5, 6): these
      materials exhibit a giant electromechanical (piezoelectric) response that is
      finding use in ultrasonic and medical applications, as well as in
      telecommunications. The origins of this effect are, however, still unclear. Here
      we show that the giant electromechanical response in PMN-PT (and potentially
      other ferroelectric relaxors) is the manifestation of critical points that define
      a line in the phase diagram of this system. Specifically, in the electric-field
      temperature-composition phase diagram of PMN-PT (the composition being varied by
      changing the PT concentration), a first-order paraelectric-ferroelectric phase
      transition terminates in a line of critical points where the piezoelectric
      coefficient is maximum. Above this line, supercritical evolution is observed. On
      approaching the critical point, both the energy cost and the electric field
      necessary to induce ferroelectric polarization rotations decrease significantly,
      thus explaining the giant electromechanical response of these relaxors.

PMID- 16791190
TI  - Broad-band optical parametric gain on a silicon photonic chip.
AB  - Developing an optical amplifier on silicon is essential for the success of
      silicon-on-insulator (SOI) photonic integrated circuits. Recently, optical gain
      with a 1-nm bandwidth was demonstrated using the Raman effect, which led to the
      demonstration of a Raman oscillator, lossless optical modulation and optically
      tunable slow light. A key strength of optical communications is the parallelism
      of information transfer and processing onto multiple wavelength channels.
      However, the relatively narrow Raman gain bandwidth only allows for amplification
      or generation of a single wavelength channel. If broad gain bandwidths were to be
      demonstrated on silicon, then an array of wavelength channels could be generated
      and processed, representing a critical advance for densely integrated photonic
      circuits. Here we demonstrate net on/off gain over a wavelength range of 28 nm
      through the optical process of phase-matched four-wave mixing in suitably
      designed SOI channel waveguides. We also demonstrate wavelength conversion in the
      range 1,511-1,591 nm with peak conversion efficiencies of +5.2 dB, which
      represents more than 20 times improvement on previous four-wave-mixing
      efficiencies in SOI waveguides. These advances allow for the implementation of
      dense wavelength division multiplexing in an all-silicon photonic integrated
      circuit. Additionally, all-optical delays, all-optical switches, optical signal
      regenerators and optical sources for quantum information technology, all
      demonstrated using four-wave mixing in silica fibres, can now be transferred to
      the SOI platform.

PMID- 16791191
TI  - The Southern Ocean biogeochemical divide.
AB  - Modelling studies have demonstrated that the nutrient and carbon cycles in the
      Southern Ocean play a central role in setting the air-sea balance of CO(2) and
      global biological production. Box model studies first pointed out that an
      increase in nutrient utilization in the high latitudes results in a strong
      decrease in the atmospheric carbon dioxide partial pressure (pCO2). This early
      research led to two important ideas: high latitude regions are more important in
      determining atmospheric pCO2 than low latitudes, despite their much smaller area,
      and nutrient utilization and atmospheric pCO2 are tightly linked. Subsequent
      general circulation model simulations show that the Southern Ocean is the most
      important high latitude region in controlling pre-industrial atmospheric CO(2)
      because it serves as a lid to a larger volume of the deep ocean. Other studies
      point out the crucial role of the Southern Ocean in the uptake and storage of
      anthropogenic carbon dioxide and in controlling global biological production.
      Here we probe the system to determine whether certain regions of the Southern
      Ocean are more critical than others for air-sea CO(2) balance and the biological
      export production, by increasing surface nutrient drawdown in an ocean general
      circulation model. We demonstrate that atmospheric CO(2) and global biological
      export production are controlled by different regions of the Southern Ocean. The
      air-sea balance of carbon dioxide is controlled mainly by the biological pump and
      circulation in the Antarctic deep-water formation region, whereas global export
      production is controlled mainly by the biological pump and circulation in the
      Subantarctic intermediate and mode water formation region. The existence of this
      biogeochemical divide separating the Antarctic from the Subantarctic suggests
      that it may be possible for climate change or human intervention to modify one of
      these without greatly altering the other.

PMID- 16791192
TI  - Interseismic strain accumulation and the earthquake potential on the southern San
      Andreas fault system.
AB  - The San Andreas fault in California is a mature continental transform fault that
      accommodates a significant fraction of motion between the North American and
      Pacific plates. The two most recent great earthquakes on this fault ruptured its
      northern and central sections in 1906 and 1857, respectively. The southern
      section of the fault, however, has not produced a great earthquake in historic
      times (for at least 250 years). Assuming the average slip rate of a few
      centimetres per year, typical of the rest of the San Andreas fault, the minimum
      amount of slip deficit accrued on the southern section is of the order of 7-10
      metres, comparable to the maximum co-seismic offset ever documented on the fault.
      Here I present high-resolution measurements of interseismic deformation across
      the southern San Andreas fault system using a well-populated catalogue of space
      borne synthetic aperture radar data. The data reveal a nearly equal partitioning
      of deformation between the southern San Andreas and San Jacinto faults, with a
      pronounced asymmetry in strain accumulation with respect to the geologically
      mapped fault traces. The observed strain rates confirm that the southern section
      of the San Andreas fault may be approaching the end of the interseismic phase of
      the earthquake cycle.

PMID- 16791193
TI  - A lamprey from the Cretaceous Jehol biota of China.
AB  - Widespread nowadays in freshwater and coastal seas of the cold and temporal
      zones, lampreys are a jawless vertebrate group that has been in existence for
      more than 300 million years but left a meagre fossil record. Only two fossil
      lamprey species, namely Mayomyzon pieckoensis and Hardistiella montanensis, have
      been recognized with certainty from North American Carboniferous marine deposits.
      Here we report a freshwater lamprey from the Early Cretaceous epoch (about 125
      million years ago) of Inner Mongolia, China. The new taxon, Mesomyzon mengae, has
      a long snout, a well-developed sucking oral disk, a relatively long branchial
      apparatus showing branchial basket, seven gill pouches, gill arches and
      impressions of gill filaments, about 80 myomeres and several other characters
      that are previously unknown or ambiguous. Our finding not only indicates
      Mesomyzon's closer relationship to extant lampreys but also reveals the group's
      invasion into a freshwater environment no later than the Early Cretaceous. The
      new material furthers our understanding of ancient lampreys, bridges the gap
      between the Carboniferous ones and their recent relatives, and adds to our
      knowledge of the evolutionary history of lampreys.

PMID- 16791194
TI  - Image scoring and cooperation in a cleaner fish mutualism.
AB  - Humans are highly social animals and often help unrelated individuals that may
      never reciprocate the altruist's favour. This apparent evolutionary puzzle may be
      explained by the altruist's gain in social image: image-scoring bystanders, also
      known as eavesdroppers, notice the altruistic act and therefore are more likely
      to help the altruist in the future. Such complex indirect reciprocity based on
      altruistic acts may evolve only after simple indirect reciprocity has been
      established, which requires two steps. First, image scoring evolves when
      bystanders gain personal benefits from information gathered, for example, by
      finding cooperative partners. Second, altruistic behaviour in the presence of
      such bystanders may evolve if altruists benefit from access to the bystanders.
      Here, we provide experimental evidence for both of the requirements in a cleaning
      mutualism involving the cleaner fish Labroides dimidiatus. These cleaners may
      cooperate and remove ectoparasites from clients or they may cheat by feeding on
      client mucus. As mucus may be preferred over typical client ectoparasites,
      clients must make cleaners feed against their preference to obtain a cooperative
      service. We found that eavesdropping clients spent more time next to
      'cooperative' than 'unknown cooperative level' cleaners, which shows that clients
      engage in image-scoring behaviour. Furthermore, trained cleaners learned to feed
      more cooperatively when in an 'image-scoring' than in a 'non-image-scoring'
      situation.

PMID- 16791195
TI  - Experience-dependent and cell-type-specific spine growth in the neocortex.
AB  - Functional circuits in the adult neocortex adjust to novel sensory experience,
      but the underlying synaptic mechanisms remain unknown. Growth and retraction of
      dendritic spines with synapse formation and elimination could change brain
      circuits. In the apical tufts of layer 5B (L5B) pyramidal neurons in the mouse
      barrel cortex, a subset of dendritic spines appear and disappear over days,
      whereas most spines are persistent for months. Under baseline conditions, new
      spines are mostly transient and rarely survive for more than a week. Transient
      spines tend to be small, whereas persistent spines are usually large. Because
      most excitatory synapses in the cortex occur on spines, and because synapse size
      and the number of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) receptors are proportional to spine volume, the excitation of pyramidal
      neurons is probably driven through synapses on persistent spines. Here we test
      whether the generation and loss of persistent spines are enhanced by novel
      sensory experience. We repeatedly imaged dendritic spines for one month after
      trimming alternate whiskers, a paradigm that induces adaptive functional changes
      in neocortical circuits. Whisker trimming stabilized new spines and destabilized
      previously persistent spines. New-persistent spines always formed synapses. They
      were preferentially added on L5B neurons with complex apical tufts rather than
      simple tufts. Our data indicate that novel sensory experience drives the
      stabilization of new spines on subclasses of cortical neurons. These synaptic
      changes probably underlie experience-dependent remodelling of specific
      neocortical circuits.

PMID- 16791196
TI  - Mammalian cochlear supporting cells can divide and trans-differentiate into hair
      cells.
AB  - Sensory hair cells of the mammalian organ of Corti in the inner ear do not
      regenerate when lost as a consequence of injury, disease, or age-related
      deafness. This contrasts with other vertebrates such as birds, where the death of
      hair cells causes surrounding supporting cells to re-enter the cell cycle and
      give rise to both new hair cells and supporting cells. It is not clear whether
      the lack of mammalian hair cell regeneration is due to an intrinsic inability of
      supporting cells to divide and differentiate or to an absence or blockade of
      regenerative signals. Here we show that post-mitotic supporting cells purified
      from the postnatal mouse cochlea retain the ability to divide and trans
      differentiate into new hair cells in culture. Furthermore, we show that age
      dependent changes in supporting cell proliferative capacity are due in part to
      changes in the ability to downregulate the cyclin-dependent kinase inhibitor
      p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian
      supporting cells are potential targets for therapeutic manipulation.

PMID- 16791197
TI  - Clonal analysis reveals a common progenitor for thymic cortical and medullary
      epithelium.
AB  - The thymus provides an essential environment for the development of T cells from
      haemopoietic progenitors. This environment is separated into cortical and
      medullary regions, each containing functionally distinct epithelial populations
      that are important at successive stages of T-cell development and selection.
      However, the developmental origin and lineage relationships between cortical and
      medullary epithelial cell types remain controversial. Here we describe a clonal
      assay to investigate the developmental potential of single, individually
      selected, thymic epithelial progenitors (marked with enhanced yellow fluorescent
      protein) developing within the normal architecture of the thymus. Using this
      approach, we show that cortical and medullary epithelial cells share a common
      origin in bipotent precursors, providing definitive evidence that they have a
      single rather than dual germ layer origin during embryogenesis. Our findings
      resolve a long-standing issue in thymus development, and are important in
      relation to the development of cell-based strategies for thymus disorders and the
      possibility of restoring function of the atrophied adult thymus.

PMID- 16791198
TI  - Formation of a functional thymus initiated by a postnatal epithelial progenitor
      cell.
AB  - The thymus is essential for the generation of self-tolerant effector and
      regulatory T cells. Intrathymic T-cell development requires an intact stromal
      microenvironment, of which thymic epithelial cells (TECs) constitute a major
      part. For instance, cell-autonomous genetic defects of forkhead box N1 (Foxn1)
      and autoimmune regulator (Aire) in thymic epithelial cells cause primary
      immunodeficiency and autoimmunity, respectively. During development, the thymic
      epithelial rudiment gives rise to two major compartments, the cortex and medulla.
      Cortical TECs positively select T cells, whereas medullary TECs are involved in
      negative selection of potentially autoreactive T cells. It has long been unclear
      whether these two morphologically and functionally distinct types of epithelial
      cells arise from a common bi-potent progenitor cell and whether such progenitors
      are still present in the postnatal period. Here, using in vivo cell lineage
      analysis in mice, we demonstrate the presence of a common progenitor of cortical
      and medullary TECs after birth. To probe the function of postnatal progenitors, a
      conditional mutant allele of Foxn1 was reverted to wild-type function in single
      epithelial cells in vivo. This led to the formation of small thymic lobules
      containing both cortical and medullary areas that supported normal thymopoiesis.
      Thus, single epithelial progenitor cells can give rise to a complete and
      functional thymic microenvironment, suggesting that cell-based therapies could be
      developed for thymus disorders.

PMID- 16791199
TI  - Nanog promotes transfer of pluripotency after cell fusion.
AB  - Through cell fusion, embryonic stem (ES) cells can erase the developmental
      programming of differentiated cell nuclei and impose pluripotency. Molecules that
      mediate this conversion should be identifiable in ES cells. One candidate is the
      variant homeodomain protein Nanog, which has the capacity to entrain
      undifferentiated ES cell propagation. Here we report that in fusions between ES
      cells and neural stem (NS) cells, increased levels of Nanog stimulate pluripotent
      gene activation from the somatic cell genome and enable an up to 200-fold
      increase in the recovery of hybrid colonies, all of which show ES cell
      characteristics. Nanog also improves hybrid yield when thymocytes or fibroblasts
      are fused to ES cells; however, fewer colonies are obtained than from ES x NS
      cell fusions, consistent with a hierarchical susceptibility to reprogramming
      among somatic cell types. Notably, for NS x ES cell fusions elevated Nanog
      enables primary hybrids to develop into ES cell colonies with identical frequency
      to homotypic ES x ES fusion products. This means that in hybrids, increased Nanog
      is sufficient for the NS cell epigenome to be reset completely to a state of
      pluripotency. We conclude that Nanog can orchestrate ES cell machinery to instate
      pluripotency with an efficiency of up to 100% depending on the differentiation
      status of the somatic cell.

PMID- 16791200
TI  - Increased cell-to-cell variation in gene expression in ageing mouse heart.
AB  - The accumulation of somatic DNA damage has been implicated as a cause of ageing
      in metazoa. One possible mechanism by which increased DNA damage could lead to
      cellular degeneration and death is by stochastic deregulation of gene expression.
      Here we directly test for increased transcriptional noise in aged tissue by
      dissociating single cardiomyocytes from fresh heart samples of both young and old
      mice, followed by global mRNA amplification and quantification of mRNA levels in
      a panel of housekeeping and heart-specific genes. Although gene expression levels
      already varied among cardiomyocytes from young heart, this heterogeneity was
      significantly elevated at old age. We had demonstrated previously an increased
      load of genome rearrangements and other mutations in the heart of aged mice. To
      confirm that increased stochasticity of gene expression could be a result of
      increased genome damage, we treated mouse embryonic fibroblasts in culture with
      hydrogen peroxide. Such treatment resulted in a significant increase in cell-to
      cell variation in gene expression, which was found to parallel the induction and
      persistence of genome rearrangement mutations at a lacZ reporter locus. These
      results underscore the stochastic nature of the ageing process, and could provide
      a mechanism for age-related cellular degeneration and death in tissues of
      multicellular organisms.

PMID- 16791201
TI  - Smad4 signalling in T cells is required for suppression of gastrointestinal
      cancer.
AB  - SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic
      cancer), is a tumour suppressor gene that encodes a central mediator of
      transforming growth factor-beta signalling. Germline mutations in SMAD4 are found
      in over 50% of patients with familial juvenile polyposis, an autosomal dominant
      disorder characterized by predisposition to hamartomatous polyps and
      gastrointestinal cancer. Dense inflammatory cell infiltrates underlay grossly
      normal appearing, non-polypoid colonic and gastric mucosa of patients with
      familial juvenile polyposis. This prominent stromal component suggests that loss
      of SMAD4-dependent signalling in cells within the epithelial microenvironment has
      an important role in the evolution of intestinal tumorigenesis in this syndrome.
      Here we show that selective loss of Smad4-dependent signalling in T cells leads
      to spontaneous epithelial cancers throughout the gastrointestinal tract in mice,
      whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising
      within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with
      dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type
      cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma
      cell and stromal expansion. The results support the concept that cancer, as an
      outcome, reflects the loss of the normal communication between the cellular
      constituents of a given organ, and indicate that Smad4-deficient T cells
      ultimately send the wrong message to their stromal and epithelial neighbours.

PMID- 16791203
TI  - Photobleaching of YFP does not produce a CFP-like species that affects FRET
      measurements.

PMID- 16791204
TI  - Photobleaching of YFP does not produce a CFP-like species that affects FRET
      measurements.

PMID- 16791206
TI  - How to find an opening (or lots of them).

PMID- 16791207
TI  - DNase-chip: a high-resolution method to identify DNase I hypersensitive sites
      using tiled microarrays.
AB  - Mapping DNase I hypersensitive sites is an accurate method of identifying the
      location of gene regulatory elements, including promoters, enhancers, silencers
      and locus control regions. Although Southern blots are the traditional method of
      identifying DNase I hypersensitive sites, the conventional manual method is not
      readily scalable to studying large chromosomal regions, much less the entire
      genome. Here we describe DNase-chip, an approach that can rapidly identify DNase
      I hypersensitive sites for any region of interest, or potentially for the entire
      genome, by using tiled microarrays. We used DNase-chip to identify DNase I
      hypersensitive sites accurately from a representative 1% of the human genome in
      both primary and immortalized cell types. We found that although most DNase I
      hypersensitive sites were present in both cell types studied, some of them were
      cell-type specific. This method can be applied globally or in a targeted fashion
      to any tissue from any species with a sequenced genome.

PMID- 16791208
TI  - Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays.
AB  - Localized accessibility of critical DNA sequences to the regulatory machinery is
      a key requirement for regulation of human genes. Here we describe a high
      resolution, genome-scale approach for quantifying chromatin accessibility by
      measuring DNase I sensitivity as a continuous function of genome position using
      tiling DNA microarrays (DNase-array). We demonstrate this approach across 1% (
      approximately 30 Mb) of the human genome, wherein we localized 2,690 classical
      DNase I hypersensitive sites with high sensitivity and specificity, and also
      mapped larger-scale patterns of chromatin architecture. DNase I hypersensitive
      sites exhibit marked aggregation around transcriptional start sites (TSSs),
      though the majority mark nonpromoter functional elements. We also developed a
      computational approach for visualizing higher-order features of chromatin
      structure. This revealed that human chromatin organization is dominated by large
      (100-500 kb) 'superclusters' of DNase I hypersensitive sites, which encompass
      both gene-rich and gene-poor regions. DNase-array is a powerful and
      straightforward approach for systematic exposition of the cis-regulatory
      architecture of complex genomes.

PMID- 16791209
TI  - Monitoring dynamic protein interactions with photoquenching FRET.
AB  - The mammalian cell nucleus is a dynamic and highly organized structure. Most
      proteins are mobile within the nuclear compartment, and this mobility reflects
      transient interactions with chromatin, as well as network interactions with a
      variety of protein partners. To study these dynamic processes in living cells, we
      developed an imaging method that combines the photoactivated green fluorescent
      protein (PA-GFP) and fluorescence resonance energy transfer (FRET) microscopy. We
      used this new method, photoquenching FRET (PQ-FRET), to define the dynamic
      interactions of the heterochromatin protein-1 alpha (HP1alpha) and the
      transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) in regions
      of centromeric heterochromatin in mouse pituitary cells. The advantage of the PQ
      FRET assay is that it provides simultaneous measurement of a protein's mobility,
      its exchange within macromolecular complexes and its interactions with other
      proteins in the living cell without the need for corrections based on reference
      images acquired from control cells.

PMID- 16791210
TI  - Dynamic proteomics in individual human cells uncovers widespread cell-cycle
      dependence of nuclear proteins.
AB  - We examined cell cycle-dependent changes in the proteome of human cells by
      systematically measuring protein dynamics in individual living cells. We used
      time-lapse microscopy to measure the dynamics of a random subset of 20 nuclear
      proteins, each tagged with yellow fluorescent protein (YFP) at its endogenous
      chromosomal location. We synchronized the cells in silico by aligning protein
      dynamics in each cell between consecutive divisions. We observed widespread (40%)
      cell-cycle dependence of nuclear protein levels and detected previously unknown
      cell cycle-dependent localization changes. This approach to dynamic proteomics
      can aid in discovery and accurate quantification of the extensive regulation of
      protein concentration and localization in individual living cells.

PMID- 16791211
TI  - Automated identification of SUMOylation sites using mass spectrometry and SUMmOn
      pattern recognition software.
AB  - Tandem mass spectrometry (MS/MS) allows for the rapid identification of many
      types of post-translational modifications (PTMs), especially those that can be
      detected by a diagnostic mass shift in one or more peptide fragment ions (for
      example, phosphorylation). But some PTMs (for example, SUMOs and other ubiquitin
      like modifiers) themselves produce multiple fragment ions; combined with
      fragments from the modified target peptide, a complex overlapping fragmentation
      pattern is thus generated, which is uninterpretable by standard peptide
      sequencing software. Here we introduce SUMmOn, an automated pattern recognition
      tool that detects diagnostic PTM fragment ion series within complex MS/MS
      spectra, to identify modified peptides and modification sites within these
      peptides. Using SUMmOn, we demonstrate for the first time that human SUMO-1
      multimerizes in vitro primarily via three N-terminal lysines, Lys7, Lys16 and
      Lys17. Notably, our method is theoretically applicable to any type of
      modification or chemical moiety generating a unique fragment ion pattern.

PMID- 16791212
TI  - Overview: methods and applications for droplet compartmentalization of biology.
AB  - Three protocols in this issue highlight applications of emulsification
      procedures, which deliver high-throughput potential to the molecular biology
      laboratory, without the need for automation. These procedures have already
      generated interesting results and spurred the development of exciting new
      technologies, while requiring only readily available laboratory equipment.

PMID- 16791213
TI  - Amplification of complex gene libraries by emulsion PCR.

PMID- 16791214
TI  - BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions.

PMID- 16791215
TI  - Directed evolution by in vitro compartmentalization.

PMID- 16791261
TI  - Concurrent use of indomethacin and dexamethasone increases the risk of
      spontaneous intestinal perforation in very low birth weight neonates.
AB  - BACKGROUND: Dexamethasone or indomethacin predisposes very low birth weight
      (VLBW) neonates to spontaneous intestinal perforation (SIP). However, no study
      has specifically investigated the role of the concurrent use of indomethacin and
      dexamethasone in SIP. OBJECTIVE: To test whether the concurrent use of
      indomethacin and dexamethasone increases the risk of SIP. METHODS: In this single
      center, retrospective, 2:1 matched, case-control study, the odds of SIP were
      assessed using univariate and multivariate logistic regression analysis in < or
      =14-day old VLBW infants. RESULTS: Sixteen VLBW infants with SIP were matched to
      32 controls by birth weight. After adjusting for clinically relevant variables,
      patients who received > or =3 doses of indomethacin for ductal closure or
      intraventricular hemorrhage prophylaxis and > or =3 doses of low-dose
      dexamethasone (0.3 mg/kg cumulative dose over 3 days) for refractory hypotension
      during the first postnatal week, were 9.6 times more likely to develop SIP [95%
      CI 1.22, 75.71]. CONCLUSIONS: The combined use of indomethacin and dexamethasone
      increases the risk of SIP in VLBW neonates.

PMID- 16791262
TI  - Hyperforin, a new lead compound against the progression of cancer and leukemia?
AB  - Extracts of the plant St John's wort, Hyperforin perforatum L., have been used
      for centuries in traditional medicine, notably for the treatment of depression.
      One of their main lipophilic components, a natural prenylated phloroglucinol
      termed hyperforin (HF), has been identified as the major molecule responsible for
      the antidepressant effects of this plant. Within the last few years, a number of
      studies have demonstrated that HF displays, in addition, several other biological
      properties of potential pharmacological interest. They include an antibacterial
      capacity and inhibitory effects on inflammatory mediators. It is worth noting
      that HF also promotes apoptosis of various cancer cells from solid tumors and
      hematological malignancies, including B-cell chronic lymphocytic leukemia. In
      addition, HF inhibits the capacity of migration and invasion of different tumor
      cells, as well as exhibiting antiangiogenic effects. Altogether, these properties
      qualify HF as a lead structure for the development of new therapeutic molecules
      in the treatment of various diseases, including some malignant tumors.

PMID- 16791263
TI  - Perforin polymorphism A91V and susceptibility to B-precursor childhood acute
      lymphoblastic leukemia: a report from the Children's Oncology Group.
AB  - Perforin plays a key role in the cytotoxicity of natural killer and cytotoxic T
      cells. Genetic mutations in the perforin gene (PRF1) give rise to approximately
      30% cases of familial hemophagocytic lymphohistiocytosis. A frequent
      polymorphism, A91V (C to T transition at position 272), may impair processing of
      perforin protein to the active form, and has been suggested to increase
      susceptibility to childhood acute lymphoblastic leukemia (ALL). To investigate
      the role of A91V in ALL, we genotyped 2272 children with de novo ALL registered
      on the Pediatric Oncology Group ALL Classification study P9900 and 655 normal
      controls. Allele frequencies in the controls showed a very low frequency of the
      variant allele in blacks, 0.7% compared to 4% in white controls. In light of
      this, analysis was restricted to a comparison of white cases and controls only.
      Overall genotype frequencies were similar in white ALL cases and normal white
      controls (P=0.58), indicating that in contrast to the previous report, A91V
      polymorphism is not associated with increased risk of childhood ALL. PRF1 A91V
      frequency was significantly increased in children with BCR-ABL positive ALL (24
      vs 8.5%; P=0.0048); however, this observation includes a relatively small number
      of cases and needs further exploration.

PMID- 16791264
TI  - Unusual immunophenotypic shift in a patient with T-cell acute lymphoblastic
      leukemia.

PMID- 16791265
TI  - Membrane-derived microvesicles: important and underappreciated mediators of cell
      to-cell communication.
AB  - Normal and malignant cells shed from their surface membranes as well as secrete
      from the endosomal membrane compartment circular membrane fragments called
      microvesicles (MV). MV that are released from viable cells are usually smaller in
      size compared to the apoptotic bodies derived from damaged cells and unlike them
      do not contain fragmented DNA. Growing experimental evidence indicates that MV
      are an underappreciated component of the cell environment and play an important
      pleiotropic role in many biological processes. Generally, MV are enriched in
      various bioactive molecules and may (i) directly stimulate cells as a kind of
      'signaling complex', (ii) transfer membrane receptors, proteins, mRNA and
      organelles (e.g., mitochondria) between cells and finally (iii) deliver
      infectious agents into cells (e.g., human immuno deficiency virus, prions). In
      this review, we discuss the pleiotropic effects of MV that are important for
      communication between cells, as well as the role of MV in carcinogenesis,
      coagulation, immune responses and modulation of susceptibility/infectability of
      cells to retroviruses or prions.

PMID- 16791266
TI  - Nucleophosmin status may influence the therapeutic decision in de novo acute
      myeloid leukemia with normal karyotype.

PMID- 16791267
TI  - Cord blood donor cell leukemia in recipients.

PMID- 16791268
TI  - Inhibition of bortezomib-induced apoptosis by red blood cell uptake.

PMID- 16791269
TI  - Differential expression of p73 isoforms in relation to drug resistance in
      childhood T-lineage acute lymphoblastic leukaemia.
AB  - The T-lineage phenotype of childhood acute lymphoblastic leukaemia (ALL) is
      associated with an increased relapse-risk and in vitro resistance to drugs as
      compared to a precursor B phenotype. Antiapoptotic isoforms of p73 that lack part
      of the transactivation (TA) domain (DeltaTA-p73, i.e. p73Deltaex2, p73Deltaex3,
      p73Deltaex2/3 and DeltaN-p73) may cause resistance to anticancer agents through
      inhibition of p53 and/or proapoptotic p73 family members (TA-p73). We demonstrate
      in our study that the expression of total p73 mRNA was higher in childhood T-ALL
      compared to controls (P=0.004). In T-ALL, the relative contribution of
      antiapoptotic DeltaTA-p73 (88%) was larger than of proapoptotic TA-p73 (12%).
      Leukaemic cells of T-ALL patients expressing higher levels of antiapoptotic p73
      were more resistant to the DNA-damaging drug daunorubicin compared to cells of
      patients with low or negative expression or these isoforms (P(trend)=0.045).
      Interestingly, p73Deltaex2 was the most abundantly expressed antiapoptotic
      isoform in daunorubicin-resistant patient cells (44% of total p73). No
      association was found between high expression of proapoptotic TA-p73 or
      antiapoptotic DeltaTA-p73 and relapse-risk. Our results suggest that childhood T
      ALL is associated with a high expression of DeltaTA-p73. These isoforms may play
      a role in cellular resistance to DNA-damaging drugs in children at initial
      diagnosis of T-ALL.

PMID- 16791270
TI  - Homoharringtonine in combination with cytarabine and aclarubicin resulted in high
      complete remission rate after the first induction therapy in patients with de
      novo acute myeloid leukemia.
AB  - To assess the efficacy and toxicity of HAA regimen (homoharritonine 4 mg/m2/day,
      days 1-3; cytarabine 150 mg/m2/day, days 1-7; aclarubicin 12 mg/m2/day, days 1-7)
      as an induction therapy in the treatment of de novo acute myeloid leukemia (AML),
      48 patients with newly diagnosed AML, aged 35 (14-57) years, were entered into
      this clinical study. The median follow-up was 26 months. Eighty-three percent of
      patients achieved complete remission (CR), and the first single course of
      induction HAA regimen resulted in CR rate of 79%. The CR rate of 100, 82 and 33%
      were achieved in patients with favorable, intermediate and unfavorable
      cytogenetics, respectively. For all patients who achieved CR, the median time
      from the initiation of the induction therapy to the evaluation of the remission
      status was 32 days. For all patients, the estimated 3 years overall survival (OS)
      rate was 53%, whereas for patients with M5, the estimated OS rate at 3 years was
      75%. The toxicities associated with HAA regimen were acceptable, and the most
      common toxicity was infection. This study suggested that HAA regimen might be a
      well-tolerable, effective induction regimen in young adult patients with AML.

PMID- 16791271
TI  - Therapeutic use of granulocyte-colony stimulating factor could conceal residual
      malignant cells in patients with AML1/ETO+ acute myelogenous leukemia.
AB  - We have experienced a number of cases of AML1/ETO+ acute myelogenous leukemia
      that showed remission based on bone marrow (BM) morphological criteria, but that
      revealed clonal abnormalities in most cells by fluorescence in situ hybridization
      (FISH). Interestingly, most of these cases had AML with AML1/ETO rearrangement.
      The malignant cells were differentiated and considered mature cells after
      granulocyte-colony stimulating factor (G-CSF) treatment. To clarify the possible
      mechanisms underlying this phenomenon, we investigated the expression levels of G
      CSFR in AML cells with AML1/ETO rearrangement by flow cytometry and real-time
      polymerase chain reaction (PCR). The number of AML1/ETO+ cells expressing G-CSFR
      at baseline was significantly higher than that of AML1/ETO- AML cells (2673 vs
      522). In addition, the G-CSFR gene was more highly expressed in AML1/ETO+ cells
      than in AML1/ETO- cells by real-time PCR. This study reveals that cases showing
      remission after treatment with G-CSF mostly had leukemia with AML1/ETO
      rearrangement. This finding might be explained by the higher expression of G-CSF
      receptor in AML1/ETO+ cells than in AML1/ETO- cells. We recommend that remission
      should be confirmed by FISH, because malignant clones can be differentiated and
      masked in morphological examination or chromosome test, especially for AML with
      AML1/ETO rearrangement.

PMID- 16791272
TI  - A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a
      late-appearing Philadelphia chromosome.

PMID- 16791277
TI  - Expression of JAGGED1 in T-lymphocytes results in thymic involution by inducing
      apoptosis of thymic stromal epithelial cells.
AB  - Proper development of the thymus and differentiation of T-lymphocytes requires
      cell-cell interactions between the developing T-lymphocytes and the thymic
      epithelia. The Delta/Serrate/Lag-2 (DSL)/Notch signal-transduction pathway is
      known to govern cell fate decisions required for proper development through
      direct cell-cell interactions. The functional consequences of specific DSL/Notch
      interactions during the development of a complex organ, such as the thymus, have
      not been thoroughly elucidated, however. In order to examine the role of DSL
      proteins during thymus development and T-lymphocyte differentiation, we targeted
      expression of JAGGED1 in T-lymphocyte progenitors via the control of the proximal
      lck promoter. Here, we report that expression of JAGGED1 in T cells causes
      premature involution of the thymus by directing thymic epithelial cells to
      undergo an apoptotic program. Adoptive transfer of JAGGED1 transgenic bone marrow
      into non-transgenic mice revealed that JAGGED1 expression on T cells does not
      alter T-cell differentiation, but is directly responsible for involution of the
      thymus. We propose that the phenotype of the lck-JAGGED1 transgenic mice is a
      direct result of specific DSL/Notch interactions and improper cell-to-cell
      signaling.

PMID- 16791278
TI  - Conserved extended haplotypes of the major histocompatibility complex: further
      characterization.
AB  - Since the complete sequencing of a human major histocompatibility complex (MHC)
      haplotype, interest in non-human leucocyte antigen (HLA) genes encoded in the MHC
      has been growing. Non-HLA genes, which outnumber the HLA genes, may contribute to
      or account for HLA and disease associations. Most information on non-HLA genes
      has been obtained in separate studies of individual loci. To comprehensively
      address polymorphisms of relevant non-HLA genes in 'conserved extended
      haplotypes' (CEH), we investigated 101 International Histocompatibility Workshop
      reference cell lines and nine additional anonymous samples representing all 37
      unambiguously characterized CEHs at MICA, NFKBIL1, LTA, NCR3, AIF1, HSPA1A,
      HSPA1B, BF, NOTCH4 and a single nucleotide polymorphism (SNP) at HLA-DQA1 as well
      as MICA, NOTCH4, HSPA1B and all five tumour necrosis factor short tandem repeat
      (STR) polymorphisms. This work (1) provides an extensive catalogue of MHC
      polymorphisms in all CEHs, (2) unravels interrelationships between HLA and non
      HLA haplotypical lineages, (3) resolves reported typing ambiguities and (4)
      describes haplospecific markers for a number of CEHs. Analysis also identified a
      DQA1 SNP and segments containing MHC class III polymorphisms that corresponded
      with class II (DRB3 and DRB4) lineages. These results portray the MHC where
      lineages containing non-HLA and HLA variants in linkage disequilibrium may
      operate in concert and can guide more thorough design and interpretation of HLA
      disease relationships.

PMID- 16791279
TI  - Novel IL-15 isoforms generated by alternative splicing are expressed in the
      intestinal epithelium.
AB  - Previous studies have identified mRNA three isoforms encoding interleukin-15 (IL
      15) that are produced through differential splicing and encode for the same
      mature IL-15 protein with two different signal peptides. Our analysis of mouse
      intestinal epithelial cells revealed two new IL-15 mRNA isoforms generated by
      different alternative splicing events. In one form (IL-15DeltaE6), exon 6 is
      absent, and in the second form the first 48 nt of exon 7 are absent (IL
      15DeltaE7) through usage of an alternative 5' splicing site within exon 7. These
      mRNA isoforms encoded in-frame IL-15 protein variants lacking either 15aa (IL
      15DeltaE6) or 16aa (IL-15DeltaE7) both utilizing the normal long signal peptide.
      Significant structural changes were predicted for these new IL-15 isoforms. RNAse
      protection assays revealed the highest expression of isoform mRNA in the
      intestinal epithelium and functional analysis of recombinant IL-15 isoform
      proteins suggested possible regulatory functions.

PMID- 16791280
TI  - Rate and related factors of dyspareunia in reproductive age women: a cross
      sectional study.
AB  - This study was conducted to determine rate and related factors of dyspareunia.
      Three hundred and nineteen women aged 15-49 years were surveyed. A questionnaire
      was used to collect data. Pelvic examinations and connective tissue disorders
      were investigated. At whole 54.5% had dyspareunia. The means of gravidity,
      parity, delivery without episiotomy and vaginal length were more in women with
      dyspareunia. Heavy lifting, chronic pulmonary obstructive disease, arthritis,
      constipation, pelvic organ prolapse and pelvic muscle strength had significant
      relation to dyspareunia. The prevalence of urinary infection, stress
      incontinence, urgency, positional changes to start or complete voiding, fecal
      straining, low back pain, digital manipulation of vagina, perineum or anus to
      complete defecation, feeling genital pain or pressure and sensation of a mass in
      vagina was more in women with dyspareunia. These factors can be considered in the
      evaluation of women, to prevent those at risk and also have better management of
      this disorder.

PMID- 16791281
TI  - Sex and the brain: the role of fMRI for assessment of sexual function and
      response.
AB  - We briefly review the technique of functional brain imaging and its application
      in the assessment of the sexual response in men and women.

PMID- 16791284
TI  - Intravenously administered oligonucleotides can be delivered to conducting airway
      epithelium via the bronchial circulation.
AB  - Topical gene transfer to the airways of cystic fibrosis (CF) patients has been
      inefficient, partly due to extracellular barriers such as sputum. In an attempt
      to circumvent these, we assessed whether airway epithelial cells can be
      transfected by intravenous (i.v.) administration of liposome-complexed or "naked"
      oligonucleotides (ODNs). The conducting airways are the likely target for CF
      therapy and are supplied by the bronchial circulation. Consequently, we assessed
      ODN transfer in the mouse trachea and main bronchi as these are supplied by the
      bronchial circulation. Liposome-protamine-DNA (LPD) complexes were detected in
      the bronchial circulation but did not transfect conducting airway epithelial
      cells, even in the presence of microvascular leakage. In contrast, 'naked' ODNs
      were delivered to 17% (inter-quartile range (IQR) 10-34%) and 35% (IQR 24-59%) of
      epithelial cells when injected at 500 microg/animal, without and with
      microvascular leakage, respectively. Two types of nuclear signal were observed;
      punctate in cells throughout the airways (3%, IQR 2-6%, and 6%, IQR 4-7%, of
      cells when delivered without and with microvascular leakage, respectively) and
      diffuse in a small number of epithelial cells in the proximal trachea. ODNs may
      be relevant to CF in a variety of ways and these data suggest one way towards
      implementing their use.

PMID- 16791285
TI  - Prevention of onset of Parkinson's disease by in vivo gene transfer of human
      hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the
      loss of dopaminergic neurons in the substantia nigra (SNi). As neurotrophic
      factors support the survival and enhance the function of dopaminergic neurons,
      gene therapy using neurotrophic factors has become the center of interest. Thus,
      we focused on hepatocyte growth factor (HGF) as a neurotrophic and angiogenic
      growth factor. At 7 days before injection of 6-hydroxydopamine into the SNi,
      stereotaxic transfection of human HGF or lacZ plasmid was performed into the
      unilateral striatum of rats. Expression of human HGF in the injected sites could
      be detected in rats transfected with HGF plasmid DNA, using immunohistochemical
      staining. Consistently, human immunoreactive HGF protein could be detected at
      least up to 12 days after transfection. Interestingly, PD rats transfected with
      lacZ demonstrated amphetamine-induced rotational asymmetry. However, transfection
      of HGF plasmid DNA resulted in significant inhibition of abnormal rotation up to
      24 weeks in a dose-dependent manner. Over 90% of dopaminergic neurons were lost
      in PD rats transfected with lacZ, whereas over 70% survived in rats transfected
      with HGF, as assessed by immunohistochemical staining. Overall, the present study
      demonstrated that overexpression of HGF prevented neuronal death in a PD rat
      model, providing a potential novel therapy for PD.

PMID- 16791286
TI  - Synergy between expression of fusogenic membrane proteins, chemotherapy and
      facultative virotherapy in colorectal cancer.
AB  - Using Chou-Talalay median effect analysis, we demonstrated in permanent and short
      term cultures of colorectal cancer cells that the expression of measles virus
      fusogenic membrane glycoproteins (FMGs) in combination with chemotherapy often
      causes over most of the cytotoxic dose range synergistic cell killing. In this
      combined treatment, we observed strongly enhanced annexin V binding and caspase
      3/7 activity when compared to single-agent treatment. Furthermore, we showed
      increased expression of heat-shock protein (Hsp)70 and Hsp90alpha, but not of
      Hsp60. In a subcutaneous HT-29 colorectal xenograft model, we demonstrated that
      the administration of a replication-defective adenoviral or herpes simplex virus
      (HSV) amplicon vector (Ad.H/F or HSV.H/F) encoding tumor-restricted FMG in
      combination with FOLFOX significantly enhanced treatment outcome when compared to
      treatment with each compound individually. To increase the fraction of tumor
      cells expressing the FMG, we trans-complemented the Ad.H/F and HSV.H/F vector
      with the respective oncolytic replication-restricted adenovirus Ad.COXDeltaMK or
      HSV-1 G47Delta vector. At the end of the observation period (day 100), eight out
      of 10 animals that received G47Delta, HSV.H/F and FOLFOX were alive and tumor
      free. Administration of the analogous adenovirus-based regimen resulted in four
      out of 10 long-term survivors. We demonstrated that the expression of FMG in
      combination with chemotherapy can significantly enhance treatment outcome, which
      is further enhanced by combination with trans-complementing oncolytic vectors.

PMID- 16791287
TI  - Angiogenic gene therapy in patients with nonrevascularizable ischemic heart
      disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus
      maximum medical treatment.
AB  - The demonstration that angiogenic growth factors can stimulate new blood vessel
      growth and restore perfusion in animal models of myocardial ischemia has led to
      the development of strategies designed for the local production of angiogenic
      growth factors in patients who are not candidates for conventional
      revascularization. The results of recent clinical trials of proangiogenesis gene
      therapy have been disappointing; however, significant limitations in experimental
      design, in particular in gene transfer strategies, preclude drawing definitive
      conclusions. In the REVASC study cardiac gene transfer was optimized by direct
      intramyocardial delivery of a replication-deficient adenovirus-containing
      vascular endothelial growth factor (AdVEGF121, 4 x 10(10) particle units (p.u.)).
      Sixty-seven patients with severe angina due to coronary artery disease and no
      conventional options for revascularization were randomized to AdVEGF121 gene
      transfer via mini-thoracotomy or continuation of maximal medical treatment.
      Exercise time to 1 mm ST-segment depression, the predefined primary end-point
      analysis, was significantly increased in the AdVEGF121 group compared to control
      at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and
      time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by
      the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire
      were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks < or
      =0.001). However, if anything the results of nuclear perfusion imaging favored
      the control group, although the AdVEGF121 group achieved higher workloads.
      Overall there was no significant difference in adverse events between the two
      groups, despite the fact that procedure-related events were seen only in the
      thoracotomy group. Therefore, administration of AdVEGF121 by direct
      intramyocardial injections resulted in objective improvement in exercise-induced
      ischemia in patients with refractory ischemic heart disease.

PMID- 16791294
TI  - Globalization of the athletic training profession.

PMID- 16791295
TI  - Is neuropsychological testing useful in the management of sport-related
      concussion?

PMID- 16791297
TI  - Outbreak of community-acquired methicillin-resistant Staphylococcus aureus skin
      infections among a collegiate football team.
AB  - CONTEXT: Methicillin-resistant Staphylococcus aureus (MRSA) was once primarily a
      hospital-acquired organism, but now community-acquired MRSA (CA-MRSA) is causing
      outbreaks among otherwise healthy sport participants. OBJECTIVE: To investigate
      MRSA skin and soft tissue outbreaks within a collegiate football team and the
      effect of infection control measures over 3 years. DESIGN: Retrospective
      analysis. SETTING: College. PATIENTS OR OTHER PARTICIPANTS: Collegiate football
      team. INTERVENTION(S): Infection control measures included education, following
      Centers for Disease Control and Prevention recommendations, nasal cultures,
      hexachlorophene 3% soap, disposable towels, and hand sanitizers. MAIN OUTCOME
      MEASURE(S): Number of MRSA infections and hospitalizations. RESULTS: Complicated
      skin and soft tissue infections (those requiring surgical debridement and/or
      hospitalization) were diagnosed in 2 (1.8%) of 107 players in 2002, 17 (15.8%) of
      107 players in 2003, and 1 (0.96%) of 104 players in 2004. CONCLUSIONS: Outbreaks
      of CA-MRSA in sports teams are very serious, and recognition is crucial.
      Treatment includes incision for proper drainage, bacterial culture and
      sensitivity, and appropriate antibiotic therapy. Infection control measures
      include educating athletes and staff, following Centers for Disease Control and
      Prevention recommendations, identifying CA-MRSA carriers with nasal cultures,
      introducing hexachlorophene 3% soap intermittently in the showers, making alcohol
      based hand sanitizers available on the field, disinfecting weight training and
      rehabilitation equipment, and using disposable towels on the field during
      practices and games.

PMID- 16791298
TI  - Functional multijoint position reproduction acuity in overhead-throwing athletes.
AB  - CONTEXT: Baseball players rely on the sensorimotor system to uphold the balance
      between upper extremity stability and mobility while maintaining athletic
      performance. However, few researchers have studied functional multijoint measures
      of sensorimotor acuity in overhead-throwing athletes. OBJECTIVE: To compare
      sensorimotor acuity between 2 high-demand functional positions and among planes
      of motion within individual joints and to describe a novel method of measuring
      sensorimotor function. DESIGN: Single-session, repeated-measures design. SETTING:
      University musculoskeletal research laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Twenty-one National Collegiate Athletic Association Division I baseball players
      (age = 20.8 +/- 1.5 years, height = 181.3 +/- 5.1 cm, mass = 87.8 +/- 9.1 kg)
      with no history of upper extremity injury or central nervous system disorder.
      MAIN OUTCOME MEASURE(S): We measured active multijoint position reproduction
      acuity in multiple planes using an electromagnetic tracking device. Subjects
      reproduced 2 positions: arm cock and ball release. We calculated absolute and
      variable error for individual motions at the scapulothoracic, glenohumeral,
      elbow, and wrist joints and calculated overall joint acuity with 3-dimensional
      variable error. RESULTS: Acuity was significantly better in the arm-cock position
      compared with ball release at the scapulothoracic and glenohumeral joints. We
      observed significant differences among planes of motion within the
      scapulothoracic and glenohumeral joints at ball release. Scapulothoracic internal
      rotation and glenohumeral horizontal abduction and rotation displayed less acuity
      than other motions. CONCLUSIONS: We established the reliability of a functional
      measure of upper extremity sensorimotor system acuity in baseball players. Using
      this technique, we observed differences in acuity between 2 test positions and
      among planes of motion within the glenohumeral and scapulothoracic joints.
      Clinicians may consider these differences when designing and implementing
      sensorimotor system training. Our error scores are similar in magnitude to those
      reported using single-joint and single-plane measures. However, 3-dimensional,
      multijoint measures allow practical, unconstrained test positions and offer
      additional insight into the upper extremity as a functional unit.

PMID- 16791299
TI  - Development and reliability of the ankle instability instrument.
AB  - CONTEXT: Functional ankle instability has been defined in a variety of ways.
      Factors that are frequently used in this definition include a history of a severe
      ankle sprain, a history of multiple ankle sprains, and a recurrent feeling of
      instability or "giving way." With all the variations in defining functional ankle
      instability, it becomes increasingly important to develop a more consistent
      framework for assessing this instability. OBJECTIVE: To develop a new ankle
      instability assessment tool, the Ankle Instability Instrument, and evaluate the
      reliability of this instrument. DESIGN: Test-retest reliability was evaluated
      using intraclass correlation coefficients (2,1) for each item, each factor, and
      the total score between test days 1 and 2. Cronbach alpha was calculated to
      estimate internal consistency of the 12 items. SETTING: Classrooms, offices,
      athletic fields, and private residences. PATIENTS OR OTHER PARTICIPANTS: College
      students (29 males, 72 females, age = 20.7 +/- 2.7 years), including 73 (72%)
      with and 28 (28%) without a history of ankle injury. MAIN OUTCOME MEASURE(S):
      Subjects were asked to complete the Ankle Instability Instrument on 2 occasions
      approximately 1 week apart. RESULTS: An exploratory factor analysis of the
      Instrument produced 3 factors and reduced it from 21 to 12 items. The factors
      accounted for 32.3%, 10.7%, and 7.0% of the variance, respectively. Together,
      these factors accounted for 50.0% of the variance in the responses to the
      Instrument. Test-retest reliability ranged from .70 (SEM = 0.28) to .98 (SEM =
      0.06) for the individual items and .95 (SEM = 1.85) for the Instrument overall.
      The Cronbach alpha coefficient was .92 for factor 1 (severity of initial ankle
      sprain), .87 for factor 2 (history of ankle instability), .81 for factor 3
      (instability during activities of daily life), and .89 for the Instrument
      overall. CONCLUSIONS: The creation of the Ankle Instability Instrument is a first
      step in recognizing a more objective way of identifying patients suffering from
      functional ankle instability. The high reliability we found shows that self
      reporting of ankle symptoms is a feasible, appropriate way to obtain information
      on the presence of instability symptoms. Additionally, through this preliminary
      study, we found 3 factors that represent unique and important components of
      functional ankle instability. Clinicians and researchers can, therefore, use
      these 12 items, either alone or in combination with other information, to
      determine if functional ankle instability is present.

PMID- 16791300
TI  - Heel lifts and the stance phase of gait in subjects with limited ankle
      dorsiflexion.
AB  - CONTEXT: Heel lifts are often prescribed as part of the treatment program for
      patients with overuse injuries associated with limited ankle dorsiflexion.
      However, little is known about how joint kinematics and temporal variables are
      affected by heel lifts. OBJECTIVE: To determine the effects of heel lifts on
      selected lower extremity kinematic and temporal variables during the stance phase
      of gait in subjects with limited ankle dorsiflexion. DESIGN: Two-way, fully
      repeated-measures design. The 2 factors were side (right or left) and walking
      condition (shoes alone, 6-mm heel lifts in shoes, 9-mm heel lifts in shoes).
      SETTING: University biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Twenty-six volunteers (21 females, 5 males) with no more than 5 degrees of ankle
      joint dorsiflexion. INTERVENTION(S): Subjects were tested in shoes alone and in
      shoes with 6-mm and 9-mm heel lifts. MAIN OUTCOME MEASURE(S): We used the
      Qualisys Motion Analysis System to measure ankle dorsiflexion excursion, maximal
      knee extension, and time to heel off during the stance phase of gait under the 3
      walking conditions. RESULTS: On the right side, ankle dorsiflexion excursion
      increased significantly with the 6-mm and 9-mm heel lifts compared with shoes
      alone (P < .05). On the left side, ankle dorsiflexion increased significantly
      with the 9-mm heels lifts over shoes alone and with the 9-mm heel lifts compared
      with the 6-mm heel lifts (P < .05). Time to heel off increased significantly for
      walking with the 9-mm heel lifts compared with shoes alone (P < .05). No
      differences were noted for maximal knee extension (P > .05). CONCLUSIONS:
      Clinicians may consider prescribing heel lifts for patients with limited
      dorsiflexion range of motion if increasing ankle dorsiflexion excursion and time
      to heel off during the stance phase of gait may be beneficial.

PMID- 16791301
TI  - Sex differences in valgus knee angle during a single-leg drop jump.
AB  - CONTEXT: Sex differences in lower extremity landing mechanics and muscle
      activation have been identified as potential causative factors leading to the
      increased incidence of anterior cruciate ligament injuries in female athletes.
      Valgus knee alignment places greater strain on the anterior cruciate ligament
      than a more neutral alignment. Gluteus medius (GM) activation may stabilize the
      leg and pelvis during landing, limiting valgus knee motion and potentially
      preventing anterior cruciate ligament injury. OBJECTIVE: To determine if frontal
      plane knee angle and GM activation differ between the sexes at initial contact
      and maximal knee flexion during a single-leg drop landing. DESIGN: Between-groups
      design. SETTING: Motion analysis laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Thirty-two healthy subjects between the ages of 18 and 30 years. INTERVENTION(S):
      The independent variables were sex (male or female) and position (initial contact
      or maximal knee flexion). MAIN OUTCOME MEASURE(S): Frontal-plane knee angle and
      GM average root mean square (aRMS) amplitude. RESULTS: At initial contact, women
      landed in knee valgus and men landed in knee varus (P < .025). At maximal knee
      flexion, both men and women were in a position of knee varus, but the magnitude
      of varus was less in women than in men (P < .025). The GM aRMS amplitude was
      greater at maximal knee flexion than at initial contact (P < .025); however, male
      GM aRMS did not differ from female GM aRMS amplitude at either position (P >
      .025). CONCLUSIONS: Women tended to land in more knee valgus before and at impact
      than men. The GM muscle activation did not differ between the sexes and, thus,
      does not appear to be responsible for the sex differences in knee valgus. The
      excessive valgus knee angles displayed in women may help to explain the sex
      disparity in anterior cruciate ligament injury.

PMID- 16791302
TI  - Postural performance and strategy in the unipedal stance of soccer players at
      different levels of competition.
AB  - CONTEXT: Sport training enhances the ability to use somatosensory and otolithic
      information, which improves postural capabilities. Postural changes are different
      according to the sport practiced, but few authors have analyzed subjects'
      postural performances to discriminate the expertise level among highly skilled
      athletes within a specific discipline. OBJECTIVE: To compare the postural
      performance and the postural strategy between soccer players at different levels
      of competition (national and regional). DESIGN: Repeated measures with 1 between
      groups factor (level of competition: national or regional) and 1 within-groups
      factor (vision: eyes open or eyes closed). Dependent variables were center-of
      pressure surface area and velocity; total spectral energy; and percentage of low
      , medium-, and high-frequency band. SETTING: Sports performance laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Fifteen national male soccer players (age = 24 +/
      3 years, height = 179 +/- 5 cm, mass = 72 +/- 3 kg) and 15 regional male soccer
      players (age = 23 +/- 3 years, height = 174 +/- 4 cm, mass = 68 +/- 5 kg)
      participated in the study. INTERVENTION(S): The subjects performed posturographic
      tests with eyes open and closed. MAIN OUTCOME MEASURE(S): While subjects
      performed static and dynamic posturographic tests, we measured the center of foot
      pressure on a force platform. Spatiotemporal center-of-pressure measurements were
      used to evaluate the postural performance, and a frequency analysis of the center
      of-pressure excursions (fast Fourier transform) was conducted to estimate the
      postural strategy. RESULTS: Within a laboratory task, national soccer players
      produced better postural performances than regional players and had a different
      postural strategy. The national players were more stable than the regional
      players and used proprioception and vision information differently. CONCLUSIONS:
      In the test conditions specific to playing soccer, level of playing experience
      influenced postural control performance measures and strategies.

PMID- 16791303
TI  - Knee joint effusion and cryotherapy alter lower chain kinetics and muscle
      activity.
AB  - CONTEXT: Cryotherapy has been shown to disinhibit the quadriceps muscle after
      joint effusion by a resting measure (Hoffmann reflex) of motor recruitment. I
      sought to determine whether cryotherapy-induced motor recruitment changes
      resulted in subsequent changes in functional movement. OBJECTIVE: To quantify
      muscle recruitment changes and knee joint function after joint effusion and
      subsequent joint cryotherapy. DESIGN: A 3 x 4 multivariate mixed-model design was
      used to compare groups (normative, effusion/control, effusion/cryotherapy) across
      time (preinjection, postinjection, 30 minutes postinjection, and 60 minutes
      postinjection). SETTING: Human performance laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Forty-five volunteers (26 males, 19 females; age = 21 +/- 2 years,
      height = 174.8 +/- 10.2 cm, mass = 78.1 +/- 15.4 kg). INTERVENTION(S):
      Experimental joint effusion was used to elicit inhibition of the quadriceps
      muscle. Cryotherapy was a treatment intervention. MAIN OUTCOME MEASURE(S): Lower
      chain peak joint torque, peak and average power, knee anterior joint reaction
      force, and average and peak vastus medialis, vastus lateralis, medial hamstrings,
      and gastrocnemius muscle normalized electromyographic activity were collected
      during the extension phase of a seated, recumbent stepping motion with a
      resistance of 36% of 1-repetition maximum and a controlled cadence of 1.5 Hz.
      RESULTS: Decreases in peak torque and peak power were observed after effusion,
      whereas no decrease was observed over time in the cryotherapy or normative
      groups. A decrease in peak vastus lateralis activity was also noted after
      effusion relative to other groups. Also, the effusion/cryotherapy group had a
      greater knee anterior joint reaction force relative to the effusion/control and
      normative groups after effusion. CONCLUSIONS: Joint cryotherapy negated movement
      deficiencies represented by knee peak torque and power decreases. This could be
      due to facilitated vastus lateralis activation relative to other groups.

PMID- 16791304
TI  - Peripheral ankle cooling and core body temperature.
AB  - CONTEXT: Exposure of the human body to cold is perceived as a stressor and
      results in a sympathetic response geared at maintaining core temperature.
      Application of ice to the periphery may lead to a decrease in core temperature,
      which may counteract the therapeutic effects of cryotherapy. OBJECTIVE: To
      determine if core temperature is lowered by the application of an ice bag to the
      ankle joint complex. DESIGN: A within-subjects, repeated-measures design.
      SETTING: The University of Virginia General Clinical Research Center. PATIENTS OR
      OTHER PARTICIPANTS: Twenty-three healthy adults aged 19 to 39 years.
      INTERVENTION(S): Subjects were admitted to the hospital on 2 separate occasions.
      During one admission, subjects had a 20-minute ice treatment applied to their
      ankles; in the other admission, a bag of marbles was applied. Temperature
      measurements were recorded at 6 time intervals: baseline (before ice
      application), immediately after ice application, 10 and 20 minutes after ice
      application, and 10 and 20 minutes after ice removal. MAIN OUTCOME MEASURE(S): We
      measured core temperature and ankle and soleus muscle surface temperatures. A
      mixed-effects model analysis of variance with repeated measures was used to
      determine if differences existed in core temperature and ankle and soleus surface
      temperatures between conditions (cryotherapy and control) and over time. RESULTS:
      Core temperature did not change after ice application or ice removal (P > 0.05).
      The average core temperatures during the cryotherapy and control conditions were
      36.72 degrees C +/- 0.42 degrees C and 36.45 degrees C +/- 1.23 degrees C,
      respectively. CONCLUSIONS: A 20-minute cryotherapy treatment applied to the ankle
      did not alter core temperature.

PMID- 16791305
TI  - Organizational influences and quality-of-life issues during the professional
      socialization of certified athletic trainers working in the National Collegiate
      Athletic Association Division I setting.
AB  - CONTEXT: Health professionals are exposed to critical influences and pressures
      when socialized into their work environments. Little is known about the
      organizational socialization of certified athletic trainers (ATs) in the
      collegiate context. OBJECTIVE: To discuss the organizational influences and
      quality-of-life issues as each relates to the professional socialization of ATs
      working in the National Collegiate Athletic Association Division I setting.
      DESIGN: A qualitative design of in-depth interviews and follow-up electronic
      interviews was used to examine the organizational socialization of ATs. SETTING:
      Participants associated with Division I athletic programs from 4 National
      Athletic Trainers' Association districts volunteered for the study. PARTICIPANTS:
      A total of 11 men and 5 women participated in the study, consisting of 14 ATs and
      2 athletic directors. DATA COLLECTION AND ANALYSIS: Interviews were transcribed
      verbatim and analyzed inductively. A peer review, member checks, and data source
      triangulation were performed to establish trustworthiness. RESULTS: Two
      categories emerged that provide insight into the experiences that affected the
      professional socialization of the ATs: organizational influences and quality-of
      life issues. The data indicate that the participants in this study were heavily
      influenced by the bureaucratic tendencies of the Division I athletic
      organizations in which they worked. The participants were extremely concerned
      about the diminished quality of life that may result from being an AT in this
      context. They were, however, able to maintain a commitment to delivering quality
      care to the student-athletes despite these influences. High work volume and low
      administrative support were commonly cited as problems, thus creating concern
      about diminished quality of life and the fear of burnout. CONCLUSIONS: The AT's
      role appears not only rewarding but also challenging. The reward is working
      closely with patients and developing an interpersonal bond; the challenge is
      dealing with a bureaucratic structure and balancing one's professional and
      personal lives to prevent burnout. Thought should be given to using intervention
      strategies to mitigate the negative influences on the AT's role.

PMID- 16791307
TI  - Atraumatic subclavian vein thrombosis in a collegiate baseball player: a case
      report.
AB  - OBJECTIVE: To introduce the case of a collegiate baseball player who suffered an
      atraumatic subclavian vein thrombosis. This case presents an opportunity to
      discuss the diagnosis and treatment of a 22-year-old male with a thrombosis of
      his right subclavian vein. BACKGROUND: Upper extremity deep venous thrombosis is
      an uncommon vascular problem, occurring primarily in young, healthy, active
      people. Although the history and symptoms are often unremarkable, the condition
      can lead to complications if not correctly recognized and appropriately treated.
      In this case, the athlete reported tightness in his right biceps muscle and upper
      back after sleeping on his shoulder. The patient denied substance abuse or
      illegal anabolic steroid use, and these possibilities were ruled out as factors
      in the diagnosis and treatment. DIFFERENTIAL DIAGNOSIS: Shoulder tendinitis,
      thoracic outlet syndrome, primary upper extremity thrombosis of the right
      subclavian vein. TREATMENT: After diagnosis, the patient was placed on blood
      thinners to dissolve the clot and referred to a vascular surgeon. The patient
      underwent a balloon angioplasty and later had the first rib removed. A second
      clot formed, and a stent was placed in the vein after the clot was removed by
      medication and another angioplasty procedure. He developed a pulmonary embolism
      during the stent procedure and was sent postoperatively to the intensive care
      unit, where he underwent therapeutic anticoagulation. After 10 weeks of therapy,
      the patient stopped all anticoagulant medication and returned to school to play
      baseball. UNIQUENESS: We present the atraumatic pathogenesis of a subclavian
      venous thrombosis in a young, active, and otherwise healthy college athlete with
      unremarkable predisposing factors. Within 24 hours after rib resection, the
      subclavian vein rethrombosed. The patient was thought to have experienced a small
      pulmonary embolus. CONCLUSIONS: Individuals who participate in athletics can
      develop atraumatic upper extremity deep venous thrombosis. Therefore, it is
      important that team physicians and certified athletic trainers be prepared to
      recognize the signs and symptoms of this condition to institute prompt,
      appropriate treatment.

PMID- 16791308
TI  - How useful are physical examination procedures? Understanding and applying
      likelihood ratios.
AB  - OBJECTIVE: To describe the calculation and interpretation of likelihood ratios
      for examination procedures performed by certified athletic trainers. BACKGROUND:
      Physical examination procedures or "special tests" are commonly taught to
      athletic training students and performed by certified athletic trainers.
      Likelihood ratios offer an approach to assessing test performance that
      incorporates estimates of sensitivity and specificity into a clinically useful
      value. We describe the calculation of likelihood ratios and the application of
      likelihood ratios to clinical decision making. RECOMMENDATIONS: The performance
      characteristics of physical examination procedures taught and practiced in
      athletic training should be considered in the planning of course materials as
      well as test interpretation after a physical examination. Research is needed to
      better understand how well physical examination procedures, when performed by
      certified athletic trainers, identify those athletes with and without specific
      musculoskeletal injuries.

PMID- 16791309
TI  - Issues in estimating risks and rates in sports injury research.
AB  - OBJECTIVE: To describe 3 measures of incidence used in sports injury
      epidemiology. BACKGROUND: To promote safety in sports, athletic trainers must be
      able to accurately interpret and apply injury data and statistics. Doing so
      allows them to more efficiently articulate this information to school
      administrators in recommending increases in medical resources, such as more
      personnel, better services, and safer facilities and equipment. DESCRIPTION:
      Using data from a study of high school sports injuries, we review incidence
      rates, epidemiologic incidence proportions, and clinical incidence. The incidence
      rate is the number of injuries divided by the number of athlete-exposures and is
      based on the epidemiologic concept of person-time at risk. It accounts for
      variation in exposure between athletes and teams and is widely used by
      researchers. The epidemiologic incidence proportion is the number of injured
      athletes divided by the number of athletes at risk. It is a valid estimator of
      average injury risk, yet it is rarely used in sports injury epidemiology to
      communicate information about such risks to nonscientists. Clinical incidence is
      a hybrid between the epidemiologic incidence proportion and the incidence rate in
      that it uses the number of injuries in the numerator but the number of athletes
      at risk in the denominator. It has been widely used in research on high school
      football injury but is neither a valid estimator of risk nor a true rate.
      ADVANTAGES: Athletic trainers who understand the causes of and risk factors for
      sport-related injury are better positioned to make safe return-to-play decisions
      and decrease the likelihood of reinjury in athletes.

PMID- 16791310
TI  - Journal writing as a teaching technique to promote reflection.
AB  - OBJECTIVE: To introduce the process of journal writing to promote reflection and
      discuss the techniques and strategies to implement journal writing in an athletic
      training education curriculum. BACKGROUND: Journal writing can facilitate
      reflection and allow students to express feelings regarding their educational
      experiences. The format of this writing can vary depending on the students' needs
      and the instructor's goals. DESCRIPTION: Aspects of journal writing assignments
      are discussed, including different points to take into account before assigning
      the journals. Lastly, various factors to contemplate are presented when providing
      feedback to the students regarding their written entries. CLINICAL ADVANTAGES:
      Journal writing assignments can benefit students by enhancing reflection,
      facilitating critical thought, expressing feelings, and writing focused
      arguments. Journal writing can be adapted into a student's clinical course to
      assist with bridging the gap between classroom and clinical knowledge. In
      addition, journals can assist athletic training students with exploring different
      options for handling daily experiences.

PMID- 16791311
TI  - Modeling anticancer drug-DNA interactions via mixed QM/MM molecular dynamics
      simulations.
AB  - The development of anticancer drugs started over four decades ago, with the
      serendipitous discovery of the antitumor activity of cisplatin and its successful
      use in the treatment of various cancer types. Despite the efforts made in
      unraveling the mechanism of the action of cisplatin, as well as in the rational
      design of new anticancer compounds, in many cases detailed structural and
      mechanistic information is still lacking. Many of these drugs exert their
      anticancer activity by covalently binding to DNA inducing a distortion or simply
      impeding replication, thus triggering a cellular response, which eventually leads
      to cell death. A detailed understanding of the structural and electronic
      properties of drug-DNA complexes and their mechanism of binding is the key step
      in elucidating the principles of their anticancer activity. At the theoretical
      level, the description of covalent drug-DNA complexes requires the use of state
      of-the-art computer simulation techniques such as hybrid quantum/classical
      molecular dynamics simulations. In this review we provide a general overview on:
      drugs which covalently bind to DNA duplexes, the basic concepts of quantum
      mechanics/molecular mechanics (QM/MM), molecular dynamics methods and a list of
      selected applications of these simulations to the study of drug-DNA adducts.
      Finally, the potential and the limitations of this approach to the study of such
      systems are critically evaluated.

PMID- 16791312
TI  - Unlocking the potential of thiaheterohelicenes: chemical synthesis as the key.
AB  - The possibility of combining the electronic properties of oligothiophenes with
      potential chiroptical properties has fueled research in the area of
      thiaheterohelicenes. Recent reports that these molecules also exhibit fascinating
      interactions with biologically important macromolecules place further emphasis on
      the need for new synthetic methods to access thiaheterohelicenes. This review
      highlights the synthetic methods currently being used to prepare
      thiaheterohelicenes and discusses the role that chemical synthesis plays in the
      exploration of the properties of these helically chiral molecules.

PMID- 16791313
TI  - Highly efficient hydrazination of conjugated nitroalkenes via imidazole or DMAP
      mediated Morita-Baylis-Hillman reaction.
AB  - Novel alpha-hydrazino-alpha,beta-unsaturated nitroalkenes, which exhibit dynamic
      phenomenon on the NMR time scale, were synthesized in excellent yields via
      imidazole or DMAP mediated Morita-Baylis-Hillman (MBH) type reaction of
      nitroalkenes with azodicarboxylates.

PMID- 16791314
TI  - Practical access to the polymer incarcerated platinum (PI Pt) catalyst and its
      application to hydrogenation.
AB  - Polymer incarcerated platinum catalysts (PI Pt) were conveniently prepared from
      PtCl(2)(COD) or H(2)PtCl(6).6H(2)O and styrene copolymers via reduction of the Pt
      sources with triethylamine, coacervation, and cross-linking. The Pt catalysts
      have been successfully applied to catalytic hydrogenation including saturation of
      heterocyclic compounds.

PMID- 16791315
TI  - Synthesis and confirmation of structure for the gibberellin GA131 (18-hydroxy
      GA4).
AB  - A general method for the hydroxylation of the 18-methyl group in gibberellins has
      been developed, as demonstrated by the successful synthesis of 18-hydroxy GA(4)
      (GA(131)) by means of a tandem process involving the conjugate addition of
      alkoxides to the alpha-methylene lactone moiety of a ring A-seco-gibberellin
      followed by an intramolecular aldol reaction.

PMID- 16791316
TI  - Inotilone and related phenylpropanoid polyketides from Inonotus sp. and their
      identification as potent COX and XO inhibitors.
AB  - By bioassay-guided isolation, phenylpropanoid-derived polyketides, including an
      unusual 5-methyl-3(2H)-furanone derivative (inotilone) with potent cyclooxygenase
      (COX) and xanthone oxidase (XO) inhibitory activities were obtained from the
      fruiting body of the mushroom Inonotus sp.

PMID- 16791317
TI  - Synthesis of tetrahydroxy perhydroaza-azulenes: tandem Johnson-Claisen
      rearrangement of D-glucose-derived allylic alcohols.
AB  - The Johnson-Claisen rearrangement of D-glucose-derived allylic alcohols 5a,b,
      afforded sugar-substituted gamma,delta-unsaturated ester in high yield.
      Conversion of the ester group to an azidomethyl group, epoxidation of the double
      bond and hydrogenation gave pyrrolidine ring skeletons 13a and 13b, which were
      transformed to tetrahydroxy perhydroaza-azulenes 1a and 1b, respectively.
      Glycosidase inhibitory activity was also evaluated.

PMID- 16791318
TI  - Design and activity of cationic fullerene derivatives as inhibitors of
      acetylcholinesterase.
AB  - Four different regioisomers of cationic bis-N,N-dimethylfulleropyrrolidinium
      salts have been prepared and evaluated as inhibitors of the enzymatic activity of
      acetylcholinesterase. These fullerene-based derivatives were found to be
      noncompetitive inhibitors of acetylthiocholine hydrolysis. Molecular modelling
      was used to describe the possible interactions between the fullerene cage and the
      amino acids surrounding the cavity of the enzyme. The cationic C(60) derivatives
      used in this study represent a new class of molecules potentially able to
      modulate the enzymatic activity of acetylcholinesterase.

PMID- 16791319
TI  - Stabilisation of transition states prior to and following eudesmane cation in
      aristolochene synthase.
AB  - The mechanistic details of the cyclisation of farnesylpyrophosphate (FPP) by
      aristolochene synthase (AS) from Penicillium roqueforti have only recently begun
      to emerge, mainly through the analysis of the reaction products generated by AS
      mutants. The reaction proceeds through several intermediates including germacrene
      A and eudesmane cation. Previous work suggested that the side chain of
      phenylalanine 178 promoted the conversion of eudesmane cation to aristolochene.
      We now report that the catalytic function of this residue during the conversion
      of eudesmane cation to aristolochene is mainly due to the large size of its side
      chain, which facilitates the hydride shift from C2 to C3, rather than its
      aromatic character. In addition, F178 appears to control the regioselectivity of
      the final deprotonation step and, together with F112, helps stabilise the
      developing positive charge on C1 after the expulsion of pyrophosphate from the
      substrate. These results complete a screen of likely active-site aromatic
      residues and establish their respective roles in the conversion of FPP to
      aristolochene.

PMID- 16791320
TI  - Hydrogel polymer appears to mimic the performance of the GroEL/GroES molecular
      chaperone machine.
AB  - Controlled protein folding/refolding remains a substantial challenge to the
      biotechnology industry. Robust and adaptable artificial polymer molecular
      chaperones could make important contributions towards solving this problem.
      Taking inspiration from the mechanism of the GroEL/GroES molecular chaperone
      machine, we report the preparation and testing of a selection of cross-linked
      thermo-responsive hydrogels, one of which is shown to assist quantitative
      refolding of a stringent unfolded protein substrate (mitochondrial malate
      dehydrogenase [mMDH]) during temperature cycling between hydrophobic and
      hydrophilic states. To our knowledge, this is the first hydrogel-only artificial
      polymer molecular chaperone to be derived, which is also potentially a generic
      artificial polymer molecular chaperone for use in a folding bioreactor.

PMID- 16791321
TI  - Efficient photosensitized splitting of the thymine dimer/oxetane unit on its
      modifying beta-cyclodextrin by a binding electron donor.
AB  - Two modified beta-cyclodextrins (beta-CDs) with a thymine dimer and a thymine
      oxetane adduct respectively, TD-CD and Ox-CD, have been prepared, and utilized to
      bind an electron-rich chromophore, indole or N,N-dimethylaniline (DMA), to form a
      supramolecular complex. We have examined the photosensitized splitting of the
      dimer/oxetane unit in TD-CD/Ox-CD by indole or DMA via an electron-transfer
      pathway, and observed high splitting efficiencies of the dimer/oxetane unit. On
      the basis of measurements of fluorescence spectra and splitting quantum yields,
      it is suggested that the splitting reaction occurs in a supramolecular complex by
      an inclusion interaction between the modified beta-CDs and DMA or indole. The
      back electron transfer, which leads low splitting efficiencies for the covalently
      linked chromophore-dimer/oxetane compounds, is suppressed in the non-covalently
      bound complex, and the mechanism has been discussed.

PMID- 16791322
TI  - Metabolism of crucifer phytoalexins in Sclerotinia sclerotiorum: detoxification
      of strongly antifungal compounds involves glucosylation.
AB  - The strongly antifungal phytoalexins brassilexin and sinalexin were metabolized
      by the stem rot fungus Sclerotinia sclerotiorum to glucosyl derivatives, whereas
      the phytoalexins brassicanal A, spirobrassinin and 1-methoxyspirobrassinin,
      displaying lower antifungal activity, were transformed via non-glucosylating
      pathways. Significantly, these transformations led to metabolites displaying no
      detectable antifungal activity. The chemical characterization of all new
      metabolites as well as the chemistry of these processes and a facile chemical
      synthesis of 1-beta-D-glucopyranosylbrassilexin are reported. Overall, our
      results indicate that phytoalexins, strongly antifungal against S. sclerotiorum,
      are detoxified via glucosylation, which in turn suggests that S. sclerotiorum has
      acquired efficient glucosyltransferase(s) that can disarm some of the most active
      plant chemical defenses. Consequently, we suggest that these glucosylation
      reactions are potential metabolic targets to control S. sclerotiorum.

PMID- 16791323
TI  - Synthesis and self-assembly of dichalcone substituted carbazole-based low
      molecular mass organogel.
AB  - We report the synthesis and self-assembly of a new pi-conjugated dichalcone
      substituted carbazole-based low molecular mass organogelator. It could form
      stable gels in most halogen-aromatic solvents. The transmission electron
      microscopy (TEM) images revealed that the gel formed fibrous structures with
      diameter of 50-100 nm, which consisted of several thinner fibers. The FT-IR, UV
      vis and XRD results suggested that the H-bonds and pi-pi interactions were the
      main driving forces for the formation of the self-assembled gel, in which the U
      shaped molecules were stacked into lamellar structures. The fluorescent spectra
      showed that the emission of the xerogel red-shifted markedly compared with the
      sol state, which resulted from the aggregation of the molecules.

PMID- 16791324
TI  - Radical reactions of [60]fullerene with beta-enamino carbonyl compounds mediated
      by manganese(III) acetate.
AB  - Manganese(III) acetate dihydrate-mediated reactions of [60]fullerene with beta
      enamino carbonyl compounds afforded [60]fullerene-fused pyrroline derivatives, of
      which the nitrogen atom is directly connected to the fullerene cage. A possible
      reaction mechanism is proposed.

PMID- 16791325
TI  - 2,5-Disubstituted pyrrolidines: synthesis by enamine reduction and subsequent
      regioselective and diastereoselective alkylations.
AB  - Methodology for the diastereoselective synthesis of 2,5-disubstituted
      pyrrolidines by reduction of enamines derived from pyroglutamic acid is reported;
      the nature of nitrogen protection was found to be critical for the stereochemical
      control of the reaction outcome. Regioselective manipulation of the C-2 and C-5
      substituents is possible, providing access to differently substituted
      pyrrolidines for a limited number of cases.

PMID- 16791326
TI  - Computational study of iminium ion formation: effects of amine structure.
AB  - Density functional calculations are used to explore the formation of iminium ions
      from secondary amines and acrolein and the subsequent reactivity of the resulting
      iminium ions. After establishing a feasible profile for this reaction in
      simulated experimental conditions, we focus on the effect of variation in amine
      structure on calculated barriers. This analysis shows that incorporation of a
      heteroatom (N or O) in the alpha-position to the reactive amine results in
      significantly reduced energy barriers, as does an electron-withdrawing group
      (carbonyl or thiocarbonyl) in the beta-position. Electron density analysis is
      used to monitor reactions at a detailed level, and to identify important
      intermolecular interactions at both minima and transition states. Barriers to
      reaction are linked to calculated proton affinities of secondary amines,
      suggesting that the relative ease of protonation-deprotonation of the amine is a
      key property of effective catalysts. Moreover, barriers for subsequent Diels
      Alder reaction of iminium ions with cyclopentadiene are lower than for their
      formation, suggesting that formation may be the rate determining step in the
      catalytic cycle.

PMID- 16791327
TI  - On-bead synthesis and binding assay of chemoselectively template-assembled
      multivalent neoglycopeptides.
AB  - The investigation of recognition events between carbohydrates and proteins,
      especially the control of how spatial factors and binding avidity are correlated
      in, remains a great interest for glycomics. Therefore, the development of
      efficient methods for the rapid evaluation of new ligands such as multivalent
      glycoconjugates is essential for diverse diagnostic or therapeutic applications.
      In this paper we describe the synthesis of chemoselectively-assembled multivalent
      neoglycopeptides and the subsequent recognition assay on a solid support.
      Aminooxylated carbohydrates (betaLac-ONH(2) 4, alphaGalNAc-ONH(2) 9 and alphaMan
      ONH(2) 13) have been prepared as carbohydrate-based recognition elements and
      assembled as clusters onto a cyclopeptidic scaffold by an oxime-based strategy in
      solid phase. Further binding tests between lectins and beads of resin derivatized
      with neoglycopeptides displaying clustered lactoses, N-acetylgalactoses and
      mannoses (18-20) have shown specific recognition and enhanced affinity through
      multivalent interactions, suggesting that the local density of carbohydrate-based
      ligands at the bead surface is crucial to improve the interaction of proteins of
      weak binding affinity. This solid phase strategy involving both molecular
      assembly and biological screening provides a rapid and efficient tool for various
      applications in glycomics.

PMID- 16791328
TI  - FluoRuGel: a versatile catalyst for aerobic alcohol oxidation in supercritical
      carbon dioxide.
AB  - FluoRuGel--a hybrid fluorinated silica glass doped with TPAP (tetra-n
      propylammonium perruthenate)--is a versatile catalyst for the aerobic oxidation
      of different alcohols in dense phase CO(2) with marked stabilization and activity
      enhancement of perruthenate upon its confinement in the sol-gel fluorinated
      silica matrix. A brief competitive analysis shows large potential rewards.

PMID- 16791329
TI  - Diastereoselective synthesis of (+/-)-(3-aminocyclopentane)alkylphosphinic acids,
      conformationally restricted analogues of GABA.
AB  - A divergent synthesis of both diastereoisomers of (+/-)-(3
      aminocyclopentane)alkylphosphinic acid is described. Both diastereoisomers are
      obtained in 5 steps from the key (+/-)-(3-hydroxycyclopent-1-ene)alkylphosphinate
      esters which are prepared via a palladium catalysed C-P bond forming reaction.

PMID- 16791330
TI  - Size matters: why nanomaterials are different.
AB  - Gold is known as a shiny, yellow noble metal that does not tarnish, has a face
      centred cubic structure, is non-magnetic and melts at 1336 K. However, a small
      sample of the same gold is quite different, providing it is tiny enough: 10 nm
      particles absorb green light and thus appear red. The melting temperature
      decreases dramatically as the size goes down. Moreover, gold ceases to be noble,
      and 2-3 nm nanoparticles are excellent catalysts which also exhibit considerable
      magnetism. At this size they are still metallic, but smaller ones turn into
      insulators. Their equilibrium structure changes to icosahedral symmetry, or they
      are even hollow or planar, depending on size. The present tutorial review intends
      to explain the origin of this special behaviour of nanomaterials.

PMID- 16791331
TI  - Insight into the construction of open-framework aluminophosphates.
AB  - Over the past twenty five years, a class of open-framework aluminophosphates,
      denoted AlPOs, has been prepared with neutral zeolitic frameworks and anionic
      frameworks showing wonderfully complex structural and compositional diversity. An
      insight into the construction of open-framework AlPOs revealing their general
      structural features and topological chemistry is provided in this tutorial
      review, and the role of templating and the designed construction and synthesis of
      AlPOs are discussed.

PMID- 16791332
TI  - The application of cathodic reductions and anodic oxidations in the synthesis of
      complex molecules.
AB  - This tutorial review surveys the recent advances in electrochemical
      transformations as they pertain to the synthesis of complex organic molecules.
      Electrochemistry has emerged as a powerful tool to synthetic chemists, yet many
      have never considered electrochemical methodology as a means for synthesis. Here,
      an introduction to electrochemistry and voltammetry will be provided with
      descriptions of the four types of electrochemical cells. In addition, recent
      examples of both anodic oxidations and cathodic reductions will be discussed,
      along with the experimental setups for carrying out each reaction.

PMID- 16791333
TI  - The use of (metallo-)supramolecular initiators for living/controlled
      polymerization techniques.
AB  - The introduction of supramolecular interactions in synthetic polymers seems to be
      a promising approach towards novel 'smart' materials that combine both the
      (reversible) supramolecular interactions and the properties of the polymers. In
      this tutorial review, the use of (metallo-)supramolecular initiators for the
      preparation of end-functionalized (metallo-)supramolecular polymers will be
      discussed in detail. The different polymerization techniques that have been
      applied as well as the different ligands and metal complexes that were used to
      initiate these polymerizations will be discussed together with the resulting
      polymer properties.

PMID- 16791334
TI  - Catalytic asymmetric synthesis of alpha- and beta-amino phosphonic acid
      derivatives.
AB  - Catalytic asymmetric reactions provide one of the most powerful and economical
      synthetic approaches to a variety of enantiomerically enriched compounds. As
      being analogues of the corresponding alpha- and beta-amino acids, optically
      active alpha- and beta-amino phosphonic acid derivatives have found widespread
      use in medicinal chemistry and the pharmaceutical sciences. Using catalytic
      amounts of chiral materials, asymmetric synthesis of enantiomerically enriched
      alpha- and beta-amino phosphonates has been a subject of growing interest. This
      tutorial review contains a compilation of the catalytic asymmetric synthetic
      methods developed to date and highlights their utility for obtaining these target
      compounds.

PMID- 16791336
TI  - Youth, sexuality, and reproduction.

PMID- 16791335
TI  - Noncovalent interactions of molecules with single walled carbon nanotubes.
AB  - In this critical review we survey non-covalent interactions of carbon nanotubes
      with molecular species from a chemical perspective, particularly emphasising the
      relationship between the structure and dynamics of these structures and their
      functional properties. We demonstrate the synergistic character of the nanotube
      molecule interactions, as molecules that affect nanotube properties are also
      altered by the presence of the nanotube. The diversity of mechanisms of molecule
      nanotube interactions and the range of experimental techniques employed for their
      characterisation are illustrated by examples from recent reports. Some practical
      applications for carbon nanotubes involved in non-covalent interactions with
      molecules are discussed.

PMID- 16791337
TI  - Conceptualization and measurement of homosexuality in sex surveys: a critical
      review.
AB  - This article reviews major national population sex surveys that have asked
      questions about homosexuality focusing on conceptual and methodological issues,
      including the definitions of sex, the measured aspects of homosexuality, sampling
      and interviewing technique, and questionnaire design. Reported rates of major
      measures of same-sex attraction, behavior, partners, and sexual identity from
      surveys are also presented and compared. The study of homosexuality in surveys
      has been shaped by the research traditions and questions ranging from sexology to
      the epidemiology of HIV/AIDS. Sexual behavior has been a central topic at least
      since Kinsey. Issues of sexual attraction and/or orientation and sexual identity
      have emerged more recently. Differences in the treatment of men and women in the
      design and analysis of surveys as well as in the reported rates in different
      surveys, in different countries and time periods are also presented and
      discussed. We point out the importance of the consideration of both
      methodological and social change issues in assessing such differences.

PMID- 16791338
TI  - [Sex as body technique: male representations of affective and sexual
      relationships].
AB  - The authors analyze male sexual initiation as a time of acquiring knowledge,
      based on 62 ethnographic interviews with young men (18-24 years) in the cities of
      Porto Alegre, Rio de Janeiro, and Salvador, Brazil, as a stage in the GRAVAD
      Research Project. Adopting an anthropological and comparative perspective, the
      reports show that men's first sexual experience is a process of physical and
      social learning by which they acquire technical knowledge on the use of their
      bodies and skill to relate to others, especially women. These are important
      milestones in the passage to adulthood. In addition to differences in belonging
      to various socioeconomic segments, the authors focus on gender relations,
      especially models of masculinity, demonstrating that a young man's first sexual
      intercourse is a socially and symbolically striking moment, not limited to a
      single event, but an experience that involves different levels of learning as
      part of the process of becoming a man.

PMID- 16791339
TI  - [Teenagers and condom use: choices by young Brazilians from three Brazilian State
      capitals in their first and last sexual intercourse].
AB  - Condom use has increased among Brazilian youth, although condoms are not used in
      all sexual relations; in addition, their use varies over the course of an
      individual's affective and sexual history. This study focused on the prevalence
      and factors associated with condom use during sexual initiation and in the most
      recent sexual relations in young men and women (18-24 years of age). The data are
      from the GRAVAD Research Project, a cross-sectional study with a stratified
      probabilistic sample using household interviews in three Brazilian State
      capitals. The analysis used multinomial logistic regression with a hierarchical
      model. Prevalence of condom use in first sexual intercourse among individuals who
      used any contraceptive method was 80.7% for females and 88.6% for males. This
      proportion dropped to 38.8% and 56%, respectively, for the most recent
      intercourse. In both events, and for both genders, condom use was associated with
      social belonging and age at initiation. Condom use at sexual initiation was
      correlated with use in the most recent intercourse (OR = 2.42 for males and 1.89
      for females). Increased condom use among youth does not mean continuing use.
      Women used condoms less than men in the events studied here.

PMID- 16791340
TI  - School trajectory and teenage pregnancy in three Brazilian state capitals.
AB  - This paper describes the relationship between school trajectory and incidence of
      teenage pregnancy. A cross-sectional residence-based questionnaire was applied,
      interviewing 4,634 youth ages 18 to 24 years, selected through a stratified three
      stage sample. For the present study, young people ages 20 to 24 years (65.6%)
      were chosen, with teenage pregnancy rates of 29.5% for females and 21.4% for
      males (in relation to their partners). Sexual debut was reported by 87% of women
      and 95.3% of men. The majority of young people reported irregular school
      trajectory, with 39% enrolled in school at the time of the study. Nearly half of
      those who had interrupted their studies at least once reported a teenage
      pregnancy. The main reasons for interrupting their studies were pregnancy and
      children for women and work for men. School dropout due to teenage pregnancy was
      mentioned by 40.1% of women for whom the outcome of pregnancy was a child.
      However, 20.5% had already dropped out of school before becoming pregnant.

PMID- 16791341
TI  - [Considering and submitting to abortion among young people in the context of
      legal prohibition: the hidden side of teenage pregnancy].
AB  - This article aims to unveil the notion of abortion as an element in young
      people's thoughts on teenage pregnancy. The study analyzes data from semi
      structured interviews with 123 young men and women 18-24 years of age in Porto
      Alegre, Rio de Janeiro, and Salvador, Brazil, belonging to different social
      strata. Based on information concerning their affective, sexual, and reproductive
      circumstances, an abortion typology was established with a gradient ranging from
      considering the act to the attempt to materialize it, actually submitting to
      abortion, and even ruling out the possibility of interrupting the pregnancy.
      According to the data, 73% of interviewees had considered the possibility of an
      abortion, demonstrating an important presence of this notion as a recourse vis-a
      vis an unpredicted pregnancy, even in the Brazilian context where abortion is
      illegal. Among the 86 young people who had experienced a pregnancy, 27 reported
      having resorted to abortion (20 males and seven females). The results indicate
      gender differences and contribute to an understanding of teenage pregnancy by
      examining induced abortion, a hidden dimension in the public and scientific
      debate on this issue.

PMID- 16791342
TI  - [Middle-class teenage sexuality and pregnancy in Rio de Janeiro, Brazil].
AB  - The subject of this paper is teenage pregnancy among middle-class youth, a topic
      not sufficiently studied in Brazil. The paper is based on a qualitative, socio
      anthropological study of 14 middle-class families in Rio de Janeiro, Brazil,
      whose children have remained single, living with their parents after the child's
      birth. A total of 25 in-depth interviews were conducted with 6 young men and 7
      young women, ages 18 to 24, and their parents (11 mothers, one father), to
      examine the event in retrospect and its impact on these young people and their
      families. Three aspects are analyzed: difficulties young people face in
      internalizing contraception as a norm; late discovery of pregnancy; and how the
      decision to either have an abortion or give birth is made by young people and
      their parents. This research allows seeing teenage pregnancy as an event that
      hinges on the process of constructing a young person's autonomy, in which
      sexuality plays a prominent role. Concluding, the phenomenon should be analyzed
      in a specific historical and cultural context, with changes over the decades in
      the rules underlying the process of individualization among young people.

PMID- 16791343
TI  - Induced abortion during youth: social inequalities in the outcome of the first
      pregnancy.
AB  - This study aimed to identify the factors associated with induced abortion in the
      first pregnancy in young women and in the first time young men got their partners
      pregnant. The methodology was a household survey with face-to-face interviews in
      a probabilistic sample in three stages with 4,634 subjects, aged 18 to 24 years
      of age residing in the cities of Salvador, Rio de Janeiro, and Porto Alegre,
      Brazil. Logistic regression analysis was used with a hierarchical strategy for
      entering variables into the model. Abortion was the reported outcome of the first
      pregnancy for 16.7% of the women and 45.9% of the men (in relation to their
      partners). Key factors associated with abortion included higher schooling and the
      occasional nature of the relationship with the male or female partner in the
      respective pregnancy. Inclusion of males in the study provided new elements for
      understanding the abortion phenomenon, including in the gender issues in
      discussion of the theme. The authors recommend greater public investment to
      warrant access to information and means for young people to achieve their
      reproductive plans in a security and healthy way, respecting their sexual and
      reproductive rights.

PMID- 16791344
TI  - [Teenage motherhood and fatherhood: observations in three cities of Brazil].
AB  - This study describes young people from 18 to 24 years of age who experienced
      motherhood and fatherhood. The data are from a multi-center study (the GRAVAD
      Research Project) conducted in the Brazilian cities of Porto Alegre, Rio de
      Janeiro, and Salvador through a household survey with a three-stage stratified
      probabilistic sample. Among a total of 4,634 interviewees, 17.9% of women and
      6.3% of men became parents before the age of 20. Young fathers and mothers show
      low schooling and early participation in the work market. Most report a per
      capita monthly family income of some 150 US dollars. The existence of children
      motivates the marital union at a young age, during which the roles of male
      provider and female caregiver are reaffirmed. Even for young parents who have
      formed a new family nucleus themselves, their own original families provide a
      basis of material and affective support.

PMID- 16791345
TI  - [Work, schooling, and reproductive health: an ethno-epidemiological study of
      adolescent women belonging to a birth cohort].
AB  - An ethno-epidemiological study was carried out with adolescent women who have
      been studied since birth. In 2001, all female adolescents from the 1982 Pelotas
      Birth Cohort were identified in 27% of all census tracts in Pelotas, Rio Grande
      do Sul State. Risk factors for childbearing during adolescence were investigated
      using a case-control approach. Cases (n = 420) were identified through the local
      live birth information system, and controls included 408 women who had not given
      birth by 2001. To understand social and cultural factors related to childbearing
      during adolescence, an ethnographic study focused on 23 young women from the case
      group. Work, schooling, sexuality, and reproductive health were analyzed using an
      ethno-epidemiological approach. Socioeconomic variables like work and schooling
      were strongly associated with childbearing in adolescence. An inverse linear
      association was observed between age at first dating and childbearing during
      adolescence (p < 0.001). Focusing on the contexts and social values (traditional
      and/or modern), pregnancy was: a positive consequence of an affective
      relationship with the partner; a way of exposing adolescent sexuality; and a
      means to achieve a certain social autonomy and other forms of social status
      within the age group.

PMID- 16791346
TI  - Sexual practices in youth: analysis of lifetime sexual trajectory and last sexual
      intercourse.
AB  - This article examines the sexual practices of young Brazilians based on data from
      the GRAVAD Research Project, a household survey targeting males and females from
      18 to 24 years of age (n = 4,634) in three Brazilian State capitals: Porto
      Alegre, Rio de Janeiro, and Salvador. The set of practices experienced over the
      course of their sexual careers is characterized by traits of social belonging,
      elements from individual life histories, and prescribed rules of conduct for men
      and women. The authors compared the young people's range of lifetime practices
      and those from last sexual relations in order to discuss the spread and
      incorporation of practices into life histories. The data point to the hegemony of
      vaginal sex in both the lifetime repertoire of sexual practices and the last
      sexual encounters, such that vaginal sex provides the prime definition of
      heterosexuality.

PMID- 16791347
TI  - [Re-signifying pain, overcoming loneliness: childbirth experiences among working
      class adolescents in a public maternity hospital in Salvador, Bahia, Brazil].
AB  - This article examines childbirth in a public maternity hospital in Salvador,
      Bahia, Brazil, from the perspective of young and adolescent women, mostly black
      and working-class. As an anthropological study, it is based on the analysis of
      birth narratives and hospital ethnography, especially in the obstetric ward. The
      women describe labor as dominated by fear, loneliness, and pain. These feelings
      are transformed into love with the birth of the child. Viewing childbirth as a
      biosocial process, the authors show how the young women construct meanings during
      the birth; meanwhile, social interactions specific to hospital birth develop,
      particularly with healthcare professionals. Symbolically, women construct birth
      as a rite of passage legitimating motherhood, against the institution's effective
      de-legitimization of sexual reproduction in low-income black mothers and
      stigmatization of adolescent motherhood.

PMID- 16791348
TI  - [Magnitude and characterization of sexual coercion experienced by young adults in
      three Brazilian state capitals: Porto Alegre, Rio de Janeiro, and Salvador].
AB  - The article estimates the magnitude of sexual coercion among young adults in
      three large Brazilian cities. In addition to evaluating prevalence, the article
      analyzes the victim's and perpetrator's characteristics, identifies the main
      strategies used in coercion, and explores the social scenarios that favor the
      occurrence of sexual violence. The article draws on data from a household survey
      called the GRAVAD Project, conducted in Porto Alegre, Rio de Janeiro, and
      Salvador and completed in 2002. Interviews were applied to a stratified sample of
      males and females aged 18-24 years, with 4,634 respondents (47.2% males and 52.8%
      females). Prevalence of some lifetime experience as victims of sexual coercion
      was estimated at 16.5% for women and 11.1% for men. Victim's and perpetrator's
      age in the first episode, the type of relationship between them, and the forms of
      pressure varied between males and females. The magnitude of such events,
      differences between men and women, and the higher prevalence rates in certain
      population sub-groups demand immediate preventive policies and strategies.

PMID- 16791349
TI  - [Adolescence, sexuality, and reproduction: cultural constructions, normative
      controversies, and interpretative alternatives].
AB  - This research note discusses the cultural and legal constructs referring to the
      sexual and reproductive rights of adolescents. Beginning with the expansion of
      human rights to include the prerogatives of children and adolescents, a veritable
      change occurred in the way families, society, and communities are expected to
      deal with these stages in life. Despite recent positive and progressive changes
      in legislation and healthcare for this age group, Brazil and other countries
      still experience difficulties in enforcing and interpreting the specific
      legislation, especially in dealing with teenage sexuality and reproduction. This
      article discusses possible alternatives and attempts to demonstrate that such
      legal reforms are not indispensable, since it is possible to weigh ethical and
      legal principles and then develop an interpretation that ensures the exercise of
      sexual and reproductive rights by adolescents.

PMID- 16791350
TI  - [Women who have sex with women: estimates for Brazil].
AB  - This paper analyzes the proportion of Brazilian women who have sex with women,
      considering three time periods. The data are from a national population-based
      survey from 1998. The proportion of the female population who reported having any
      same-sex relations during their lifetime decreased from 3% to 1.7% in the
      previous five years and remained at 1.7% in the last year. Comparing the data by
      gender, the results suggest that women and men have different patterns of
      homosexual and heterosexual experiences over the course of their lives.

PMID- 16791351
TI  - Specific language impairment: linguistic and neurobiological aspects.
AB  - Specific language impairment (SLI) occurs when children present language
      maturation, at least 12 months behind their chronological age in the absence of
      sensory or intellectual deficits, pervasive developmental disorders, evident
      cerebral damage, and adequate social and emotional conditions. The aim of this
      study was to classify a group of children according to the subtypes of SLI and to
      correlate clinical manifestations with cortical abnormalities. Seventeen children
      with SLI were evaluated. Language assessment was based on standardized test
      (Peabody) and a non-standardized protocol, which included phonological,
      syntactical, semantical, pragmatical and lexical aspects of language. All
      children, except one, had abnormal MRI. Thirteen children presented perisylvian
      polymicrogyria. The MRI findings in the remaining three patients were: right
      frontal polymicrogyria, bilateral fronto-parietal atrophy, and hypogenesis of
      corpus callosum with Chiari I. The data show that patients with posterior
      cortical involvement tended to present milder form of SLI (no sign of
      articulatory or bucofacial praxis disturbance), while diffuse polymicrogyric
      perisylvian cortex usually was seen in patients who presented severe clinical
      manifestation, mainly phonological-syntactic deficit. In conclusion, SLI may be
      associated with perisylvian polymicrogyria and clinical manifestation may vary
      according to the extent of cortical anomaly.

PMID- 16791352
TI  - Cerebrovascular disorders in childhood: etiology, clinical presentation, and
      neuroimaging findings in a case series study.
AB  - OBJECTIVE: To describe the main etiologies, neurological manifestations and neuro
      imaging findings among children with sequelae of cerebrovascular disorders.
      METHOD: Case series study of children whose diagnosis was stroke sequelae.
      Variables studied were age at the time of first episode, number of episodes,
      etiology, motor deficits, epilepsy, and effected vascular territory. RESULTS:
      Twenty three patients were studied. Average age at first episode was 6.91 (+/
      2.08) years. Fourteen patients were female. The number of stroke events per
      patient ranged from one to five. The most frequent etiologies were heart disease
      and sickle cell anemia. The most frequent neurological deficit was right
      hemiparesis. Nine patients experienced seizures. The left middle cerebral artery
      was the most affected vascular area. CONCLUSION: Our findings are similar to
      those described in the literature. Despite a careful investigation, some causes
      of stroke remain unidentified.

PMID- 16791353
TI  - Mental retadation: a MRI study of 146 Brazilian children.
AB  - We report results of a magnetic ressonance imaging (MRI) study of 146 Brazilian
      children, whose intelligence quotient scored less than 70. 50% of MRI
      examinations did not exhibit any signal of structural lesion (N group), whereas a
      focal thinning at the junction of the body and splenium of the corpus callosum;
      ventricular asymmetry; periventricular leukomalacia; gliosis and arachnoid cysts
      were among the most frequent findings in the remaining of subjects (L group).
      Maternal stress and altered blood pressure were the most frequent findings in the
      pre-natal history of both N and L children. Familial antecedents of mental
      deficiency were reported in 30% of both groups, whereas familiar history of
      alcoholism was important in N group (60% in N versus 0% in L groups).
      Neuropsychomotor development was delayed in 80% of the children in both groups.
      Aggressiveness is the most frequent finding in the post-natal children history.

PMID- 16791354
TI  - Occipital intermittent rhythmic delta activity in absence epilepsy.
AB  - Occipital intermittent rhythmic delta activity (OIRDA) is considered good
      prognostic factor in typical absences (TA). We report electroclinical evolution
      in 14 patients with TA and OIRDA, which performed video-EEG. Seven patients were
      female; 9 had childhood absence epilepsy and the others did not present
      electroclinical characteristics for syndromic classification according to ILAE's
      classification (1989). Pyknolepsy was referred to in 13; TA was the only seizure
      type in 13; one had generalized tonic-clonic seizures (GTCS) and three had
      myoclonic jerks during TA. VPA monotherapy controlled seizures in 11, diVPA and
      ESM, in one each. After seizure control EEG normalized in 10 while in three,
      spike-wave complexes (SWC) persisted, accompanied by OIRDA in one. Finally in
      another, seizures were not controlled and SWC and OIRDA persisted. In conclusion,
      we observed in this series of TA and OIRDA with onset before 10 years, pyknolepsy
      as common finding and few GTCS. VPA controlled seizures in most cases and EEG
      normalized in 76.92%. We suggest that OIRDA could be considered good prognostic
      factor in TA associated with SWC and of epileptiform nature leading to
      appropriate investigation.

PMID- 16791355
TI  - Pharmacovigilance in epileptic patients using antiepileptic drugs.
AB  - OBJECTIVE: To investigate the occurrence of adverse effects of antiepileptic
      drugs (AED) in chronic epileptic patients in mono or polytherapy. METHOD: We
      evaluated consecutive patients that met the following inclusion criteria: age of
      18 years or older, diagnosis of epilepsy for at least one year, stable dose of
      AED for at least three months. Patients were asked if they had any adverse event
      related to the AED. After that, they were interviewed according to a detailed
      semi-structure questionnaire. We also assessed specifically the adverse events in
      the last four weeks. The data were analyzed regarding the use of monotherapy x
      polytherapy, and the presence of probable depression (score>15) according to the
      Center for Epidemiologic Studies Depression Scale. RESULTS: Sixty-five patients
      were evaluated, 35 women, mean age 38.3 years; 35 patients were in use of
      monotherapy and 35 in polytherapy. Only 45 (69.2%) patients spontaneously
      reported adverse effects. After the formal questionnaire, 63 (97%) patients
      referred experiencing an adverse event (p<0.001). Seventeen men had adverse
      events, as opposed to 28 women (p=0.042). When the last four weeks were
      evaluated, patients with probable depression presented adverse events more
      frequently (p<0.0001). CONCLUSION: Our data suggest that adverse events are
      highly prevalent when a detailed questionnaire is applied and that depression may
      aggravate the number and intensity of side effects in patients using AEDs.

PMID- 16791356
TI  - Theory of mind and the frontal lobes.
AB  - BACKGROUND: Theory of mind (ToM) is the ability to attribute mental states to
      other individuals. Its cerebral organization is not enough established, even
      though the literature suggests the relevant role of the frontal lobes. OBJECTIVE:
      To evaluate frontal lobe patients and controls in ToM tests. METHOD: We studied
      20 patients with lesions limited to the frontal lobes (as shown by CT or MRI),
      and 10 normal control subjects by means of ToM tests (recognizing himself in
      mirrors, false belief, first and second order ToM tasks), as well as tests of
      other cognitive functions (counter-proofs). RESULTS: Patients and controls
      performed similarly in ToM tests. There was significant difference between
      frontal subgroups (left, right, bifrontal) in the double-bluff task (second order
      ToM) (p=0.021), without relation to verbal fluency (p=0.302) or delayed recall
      ability (p=0.159). The only two patients with deficits in ToM tasks had
      impairment of social behavior. CONCLUSION: Frontal lesions do not necessarily
      implicate in ToM deficits, which may occur when such lesions are associated to
      disturbance of social behavior.

PMID- 16791357
TI  - Cognitive dysfunction in congestive heart failure: transcranial Doppler evidence
      of microembolic etiology.
AB  - Cognitive symptoms are common in patients with congestive heart failure (CHF) and
      are usually attributed to low cerebral blood flow. In the present study, we aimed
      to evaluate global cognitive function (Mini Mental State Exam MMSE) in relation
      to both cardiac function (evaluated by echocardiogram) and cerebrovascular
      hemodynamics (evaluated by transcranial Doppler TCD) in CHF patients. In 83
      patients studied, no correlation was found between echocardiographic parameters
      and MMSE scores. In contrast, a significant correlation was found between right
      middle cerebral artery (RMCA) mean flow velocity and MMSE score (r=0.231
      p=0.039), as well as between RMCA pulsatility index and MMSE score (rs= -0.292
      p=0.015). After excluding patients with a previous history of stroke, only RMCA
      pulsatility index correlated with MMSE score (rs=-0,314 p=0,007). The
      relationship between high cerebrovascular resistance and worse cognitive scores
      suggest that microembolism may be responsible for a significant proportion of
      cognitive symptoms in CHF patients.

PMID- 16791358
TI  - Are the angiotensin-converting enzyme gene and activity risk factors for stroke?
AB  - Stroke is a multifactorial disease in which genetic factors play an important
      role. This study was carried out to determine angiotensin-converting enzyme (ACE)
      gene polymorphism in Turkish acute stroke patients and to establish whether there
      is an association of angiotensin-converting enzyme gene I/D polymorphism with
      clinical parameters. In this study 185 patients and 50 controls were recruited.
      We have investigated the association among the allelic distribution of the
      insertion/deletion (I/D) polymorphism of the ACE gene identified by polymerase
      chain reaction. Distribution of ACE gene I/D genotypes and allele frequencies in
      patients were not significantly different from controls. D allele frequencies
      were 57.8% in patients versus 53.0% in controls and I allele 42.2% versus 47%
      respectively. History of hypertension, stroke, renal, heart and vessel diseases
      incidence and age, gender, systolic-diastolic blood pressures and creatinine
      levels were significantly high in patients. But these results and ACE activities
      had no significant differences among the ACE genotypes in patients and controls.
      Our results suggest that the ACE gene polymorphism is not associated with the
      pathogenesis of stroke in Turkish stroke patients.

PMID- 16791359
TI  - Association of cytokines, neurological disability, and disease duration in
      HAM/TSP patients.
AB  - OBJECTIVE: To identify clinical and immunological markers associated with HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: 237 HTLV-I
      infected individuals were clinically assessed. They were classified according to
      the Expanded Disability Status Scale (EDSS) and Osames Motor Disability Score
      (OMDS). Cytokine levels were determined in HTLV-I seropositive individuals.
      RESULTS: 37 patients had HAM/TSP. There was a correlation between the degrees of
      disability assessed by both scales. There was also a correlation between the
      duration of HAM/TSP and the severity of disability assessed by either EDSS or
      OMDS. Higher levels of IFN-gamma were detected in unstimulated peripheral blood
      mononuclear cells (PBMC) from HAM/TSP patients as compared with HTLV-I carriers.
      CONCLUSION: This study shows the validity of the neurological scales to classify
      the degree of neurological disability in HTLV-I carriers and suggests a
      progressive behavior of HAM/TSP. This study also shows that IFN-gamma in PBMC
      supernatants are markers of HAM/TSP.

PMID- 16791360
TI  - Spinocerebellar ataxia type 7 (SCA7): family princeps history, genealogy and
      geographical distribution.
AB  - We conducted a 320 year retrospective survey of the history and genealogy of a
      large Brazilian family with SCA7. The ancestral couple was from the State of
      Ceara, Brazil, and the genealogical tree was composed of 577 individuals,
      including 217 males (37.6%), 255 females (44.1%) and 105 individuals of unknown
      sex (18.1%). Based on collected information, the 118 individuals consistently
      affected were distributed in generations IV (n=2), V (n=28), VI (n=57), VII
      (n=25) and VIII (n=6) of the genealogical tree. Sixty affected members are alive,
      37 of them (61.6%) live in the Northeast region, 12 (20%) in the Southeast, 9
      (15%) in the Center-West and 2 (3.3%) in the North. This genealogical survey was
      based only on 4 of the 10 children of the ancestral couple since the destiny of
      the remaining 6 is unknown. We propose that other Brazilian families with SCA7
      may have the same genetic origin.

PMID- 16791361
TI  - Spectral F-test power evaluation in the EEG during intermittent photic
      stimulation.
AB  - Intermittent photic stimulation (IPS) is an important functional test, which can
      induce the photic driving in the electroencephalogram (EEG). It is capable of
      enhancing latent oscillations manifestations not present in the resting EEG.
      However, for adequate quantitative evaluation of the photic driving, these
      changes should be assessed on a statistical basis. With this aim, the sampling
      distribution of spectral F test was investigated. On this basis, confidence
      limits of the SFT-estimate could be obtained for different practical situations,
      in which the signal-to-noise ratio and the number of epochs used in the
      estimation may vary. The technique was applied to the EEG of 10 normal subjects
      during IPS, and allowed detecting responses not only at the fundamental IPS
      frequency but also at higher harmonics. It also permitted to assess the strength
      of the photic driving responses and to compare them in different derivations and
      in different subjects.

PMID- 16791362
TI  - Effect of glycemic state in rats submitted to status epilepticus during
      development.
AB  - The effect of glycemic state on status epilepticus (SE) development was studied
      in animals of different ages, submitted to pilocarpine model of epilepsy. Groups:
      I- Rats with 9-day-old (P9): IA. Submitted to 1SE; IB. Saline-treated; IC.
      Induced- hyperglycemia; ID. Induced- hyperglycemia+SE; II- Rats submitted to
      three consecutive episodes of SE at P7, P8 and P9; III- Rats submitted to 1SE at
      P17; IV- Rats submitted to 1SE at P21. Hippocampal cell death and the expression
      of glucose transporter GLUT3 were analyzed in group I. The results demonstrated
      normoglycemia in the groups IA, IB and II, hypoglycemia in group III and
      hyperglycemia in group IV, showing that the glycemia during SE is age dependent.
      Induced hyperglycemia during SE in P9 protected the hippocampal neurons from
      death and both groups IC and ID presented increased GLUT3 expression, showing
      high glucose consumption by the hippocampus.

PMID- 16791363
TI  - OSP-Immunofluorescent remyelinating oligodendrocytes in the brainstem of
      toxically-demyelinated Wistar rats.
AB  - Central nervous system (CNS) remyelination following toxically-induced
      demyelination is a well known process. Oligodendrocytes constitute the bulk of
      the myelinating cells in the brain whereas Schwann cells overwhelm
      oligodendrocytes numbers in spinal cord remyelination. Despite the common
      knowledge of these facts, we still do not know completely the origin of both
      remyelinating cells. The present study investigated the participation of mature
      oligodendrocytes in remyelination after ethidium-bromide (EB) induced
      demyelination in the brainstem of normal and cyclosporin A-immunosuppressed
      Wistar rats. Thirty adult female rats were divided into three experimental
      groups. In group 1 the rats received a single intracisternal injection of 10
      microL of 0.1% ethidium bromide (EB) in 0.9% saline (n=10); in group 2 the rats
      received the EB injection while immunosuppressed with cyclosporin A (n=10); in
      group 3 the rats received a single 10 microL injection of 0.9% saline while
      treated with cyclosporin A. The rats were killed at 15, 21 and 31 days after
      injection. Within the EB lesions, from 15 days onward many cells within the
      periphery of the lesions stained positive for OSP (oligodendrocyte specific
      protein) a marker for mature oligodendrocytes and myelin. This cell marking
      signals that, at least, part of the process of repairing the myelin sheaths is
      carried out by mature cells of the oligodendrocyte lineage.

PMID- 16791364
TI  - [Role of patent foramen ovale and of the Eustaquian valve in the trhomboembolic
      events].
AB  - The association between patent foramen ovale (PFO) and paradoxical emboli is
      described in medical literature. When have not association with atrial septal
      aneurysm, arguments arise about the clots origin, because it have been difficult
      to gave evidence of the clots passing from venous circulation across shunt right
      to left. We describe four cases of vascular events whose transesophageal
      echocardiography showed clots nailed within the PFO associated the prominent
      Eustachian valve, without septal aneurysm. This paper aim to illustrate and to
      warm about the potentially role of the PFO and Eustachian valve in the
      paradoxical embolism.

PMID- 16791365
TI  - [Microsurgical anatomy of the human basal anterior perforated substance].
AB  - The anterior perforated substance (APS) is a landmark in the basal forebrain. It
      has a basal face located above the carotid bifurcation in the subarachnoid space,
      and an interhemispheric one. It is the site of passage of the arteries to the
      caudate nucleus, putamen, internal capsule, adjacent areas of the globus pallidus
      and thalamus. Fifty hemispheres from twenty-five adult cadavers were obtained.
      The arteries were perfused with colored latex, Batsons resin and gelatin colored
      with carmine. Using a surgical microscope we have determined the origin, local
      and number of origin from the parent vessel. The sites of penetration in the
      mediolateral and anteroposterior direction were also recorded. The anterior
      communicating artery contribution to the basal APS was reviewed. Significant
      vascular variations and anastomoses were encountered mainly involving middle
      cerebral and anterior choroidal arteries. The precise understanding of these
      vessels has surgical and clinical implications in the management of vascular and
      tumoral maladies related to the anterior perforated substance.

PMID- 16791366
TI  - [Inhibition of peridural fibrosis after laminectomy using biological sheet in rat
      model].
AB  - The prevention of fibrosis after lumbar and thoracic laminectomies by avoiding
      herniation of muscular tissue was studied using Wistar-EPM rats with a biological
      membrane made of decorticated bone of bovine material. The rats were sacrificed
      after eight, sixteen and twenty four weeks and the material was sent to
      anatomopathological study. This membrane proved to be biocompatible and its
      efficacy was seen by allowing formation of bone and preventing muscular tissue
      invasion of the epidural space and avoiding adherences.

PMID- 16791367
TI  - [Biologic artifacts in quantitative EEG].
AB  - We studied the influence of five biologic artifacts sources on quantitative EEG
      (blinking, forced eyes closure, forced jaw closure, tongue movements and pursuit
      eyes movements) through both visual and spectral analysis, with the purpose of
      verifying how do these artifacts can be seen in a cartographic way. We found that
      the spectrums potentials showed the same topographic display that was found
      through visual analysis. Visual analysis was superior than the quantitative
      evaluation to recognise the artifacts, as the former preserved the morphological
      display of the paroxysms. However it is important know how do the potentials are
      represented in quantitative maps, so that they can be identified as artifacts and
      not as pathologic EEG activity.

PMID- 16791368
TI  - [Central nervous system paracoccidioidomycosis: analysis of 13 cases].
AB  - Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by
      Paracoccidioides brasiliensis, prevalent in Latin America, particularly in
      Brazil. Central nervous system (CNS) involvement occur in about 10% of cases.
      Thirteen patients with PCM involving CNS were studied considering clinical
      manifestation, neuroradiology and treatment modalities. Age ranged from 30 to 71
      years-old (M=47.1+/-11.6 Me=46). There were eleven men and two women. The most
      frequent symptoms were motor deficits (53.8%), cognitive disturbance (53.8%),
      weight loss (46.1%), headaches (46.1%) and seizures (46.1%). The diagnosis was
      confirmed by the demonstration of P. brasiliensis. Granulomatous forms were
      present in all patients. Four (30.8%) of them had also meningeal involvement
      (mixed form). Computerized tomography (CT) scans were obtained in all cases and
      magnetic resonance imaging (MRI) was used in one case. Serology for HIV was done
      in ten patients (76.9%), and all the tests were negatives. Amphotericin B was
      used in twelve patients (92.3%), one of them by intraventricular infusion. In
      eight patients (61.5%), trimethopim and sulfamethoxazole were used, and, in two
      (15.4%), sulfadiazine and pirimetamine. Fluconazole, ketoconazole and
      itraconazole were each one used in a different patient as well. Six patients died
      (46.1%) and seven (53.9%) had satisfatory outcome. The follow-up period ranged
      from 2 to 74 (M=30.9) months. In conclusion, the CNS involvement in
      paracoccidioidomycosis is more frequent and more serious than thought before. The
      clinical manifestations, CT scans and MRI findings are not specific of
      paracoccidioidomycosis.

PMID- 16791369
TI  - [Relationship between adverse neural tension and nerve conduction studies in
      patients with symptoms of the carpal tunnel syndrome].
AB  - The purpose of this study was to evaluate, through a series of cases, the
      relationship between the adverse neural tension of median nerve (ANTm) and the
      electrophysiological involvement in 38 patients with symptoms of the carpal
      tunnel syndrome (CTS), submitted to nerve conduction studies (NCS). The main
      measures had been ANTm (in degrees) obtained through the test of neural tension
      provocation (TNTP) and parameters of the NCS, divided into three groups: normal,
      without severe electrophysiological alteration and with severe
      electrophysiological alteration. Significant correlations were found between ANTm
      and parameters of the NCS (p<0.05), as well as between ANTm and the three groups
      defined by the electrophysiologic alteration (rs=+0.437, p=0.002). The TNAm
      values were significantly higher in the arms with electrophysiologic diagnoses
      (p=0.007). It is suggested that the ANTm does have a participation in the
      physiopathology of the CTS, and the use of therapeutical procedures that diminish
      the development of neural tension.

PMID- 16791370
TI  - [Fatigability evaluation on multiple sclerosis patients by using a hand held
      dynamometer].
AB  - Fatigue is one of the most common disabling symptoms in multiple sclerosis (MS).
      The aim of this study was to evaluate the fatigability on patients with MS by the
      application of hand grip isotonic and isometric exercises with dynamometer. As
      results the fatigability, the isometric strength and time were statistically
      similar in the control group and in MS. We conclude that although fatigue is a
      frequent subjective complaint on MS, the fatigability and the recover after
      exercises seems to be normal.

PMID- 16791371
TI  - [Birth weight as predictor for the severity of neonatal brain white matter
      lesion].
AB  - To analyze the association of natal factors with the severity of neonatal brain
      white matter lesion (WML) by controlling the birth weight, we identified newborns
      with WML who were divided into: those with WML evolution towards resolution of
      the ultrasound image (less severe), and those who evolved with cist formation
      and/or ventriculomegalia and/or hemorrhage (greater severity). There were
      differences among the twelve variables (hyponatremia, anemia, infection,
      retinopathy, broncopulmonary dysplasia, hypoalbuminemia, persistence of the
      arterial canal, altered audiometry, early respiratory distress, birth weigh below
      2,500 g, weight per category, and prematurity) between the two groups (p<0.05),
      being that nine variables (hyponatremia, infection, retinopathy, hypoalbuminemia,
      persistence of the arterial canal, early respiratory distress, low weight,
      prematurity, and weight per category) remained statistically different (p<0.01)
      after the logistic regression analysis. When the variables were analyzed by birth
      weight category none of them presented statistical significance. This study
      suggests that birth weight is the major factor--likely the only one--associated
      to the severity of neonatal brain white matter lesion.

PMID- 16791372
TI  - [Quality of life and autism].
AB  - OBJECTIVE: To evaluate the index quality of life (QL) in bearers of including
      upset of the development. METHOD: 20 autistic children, between 4 and 12 years,
      submitted to the diagnostic evaluation by autistic traces scale-ATA and for the
      Vineland adaptive behavior scales, needing to obtain in this a quotient of
      superior development over 70. The data about QL were obtained by the scale of
      quality of life-AUQEI and compared from the application of Vineland and of AUQEI
      in a population of normal children, resembling in the sex and in the age.
      RESULTS: In the evaluation of the ATA, average was 33.75 with 4.95 standard
      deviation. The indexes of Vineland suggest that normal children have larger
      probability to present level of appropriated adaptative behavior than autistic
      children (p=0.0196). Concerning QL, the general indexes are the same for both
      groups, indicating positive QL (p=0.744). In the sub domain autonomy, autistic
      children present higher index (p=0.0048). CONCLUSION: Autistic children present
      similar indexes of QL than normal children.

PMID- 16791374
TI  - Atypical presentation of Prader-Willi syndrome with Klinefelter (XXY karytype)
      and craniosynostosis.
AB  - Prader-Willi syndrome is a mental retardation genetic disorder also characterized
      by hypogonadism, hyperphagia and obesity. We report on a four-years-old boy, born
      to consanguineous parents, with uncommon co-occurrence of Prader-Willi syndrome,
      47,XXY karyotype (Klinefelter syndrome) and coronal craniosynostosis. These are
      different unrelated conditions and it was not described before in the same
      patient to the best of our knowledge.

PMID- 16791373
TI  - Cerebral metastasis of cervical uterine cancer: report of three cases.
AB  - Cervical uterine cancer (CUC) spreads locally (pelvis and paraortic lymphnodes)
      or distantly (lungs, liver and bones). Metastasis to central nervous system (CNS)
      are rare. There are about 80 cases reported in the literature. Outcome is poor
      and survival varies from 3 to 6 months. Three cases of CNS metastasis from CUC
      are reported, one infratentorial and two supratentorials in location. In one
      patient, the initial manifestation was due to the cerebral lesion, a feature
      reported for the first time. All cases were treated by surgery, radiotherapy
      and/or chemotherapy. Clinical findings and treatment options of these rare
      lesions are reviewed.

PMID- 16791375
TI  - Spontaneous artery dissection in a patient with Human Immunodeficiency Virus
      (HIV) infection.
AB  - BACKGROUND: The relationship between human immunodeficiency virus infection and
      stroke may be attributed in some cases to an underlying vasculopathy such as in
      spontaneous cervical arteries dissections. CASE REPORT: We report the case of an
      HIV-infected patient who developed a Wallemberg's syndrome due to a vertebral
      artery dissection. Screening laboratory exams showed hyperhomocysteinemia and
      also high C-reactive protein plasma levels. CONCLUSIONS: This is the first case
      describing the association between arterial dissection (AD) and HIV-infection. We
      suggest that AD should also be remembered as a possible mechanism of ischemic
      stroke in HIV-infected patients.

PMID- 16791376
TI  - Neurocysticercosis and microscopic hippocampal dysplasia in a patient with
      refractory mesial temporal lobe epilepsy.
AB  - Epidemiologic studies suggest that neurocysticercosis (NC) is the main cause of
      symptomatic epilepsy in developing countries. The association between NC and
      mesial temporal lobe epilepsy (MTLE) has been reported by several authors. Recent
      data have shown that the presence of NC does not influence the clinical and
      pathological profile in MTLE patients and suggest that not all cysticercotic
      lesions are inevitably epileptogenic. We describe a 50-years-old woman with
      partial seizures due to NC which evolve to MTLE. The patient was submitted to a
      corticoamygdalohippocampectomy to treat refractory epilepsy. An
      immunohistochemical study using neuronal markers was made on hippocampal
      formation. Besides the typical aspects of Ammon's horn sclerosis (AHS), the
      microscopic examination demonstrates cellular features of hippocampal
      malformation including dysmorphic neurons and focal bilamination of granular cell
      layer. We suggest that, in this case, a developmental disorder lowered the
      threshold for the NC-induced seizures and contributed to the establishment of
      refractory epilepsy.

PMID- 16791377
TI  - [Emery-Dreifuss muscular dystrophy: case report].
AB  - The Emery-Dreifuss muscular dystrophy is a form of muscular dystrophy that
      frequently presents early contractures and cardiac conduction defects, caused by
      emerin deficiency in the inner nuclear membrane of the muscular fibers. A 19
      years-old man it presented muscle weakness and hypotrophy in the proximal upper
      and lower limbs, dysphagia and early contractures in elbows and ankles, with
      familiar history compatible with X-linked inheritance form. The investigation
      showed increased serum creatinekinase levels electrocardiogram had a first degree
      atrioventricular block and right bundle branch block normal electromyography and
      nerve conduction study muscle biopsy disclosed myopathic characteristics and
      nuclear protein immunohystochemical analysis showed deficiency of emerin. The
      clinical and genetics manifestations, laboratorial and electromyography changes,
      as well as, the study of the pattern of inheritance for genetic counseling are
      discussed.

PMID- 16791378
TI  - [Neurophysiological study in slow-channel congenital myasthenic syndrome: case
      report].
AB  - The slow-channel syndrome is one of the congenital myasthenic syndromes
      attributed to inherited kinetic disorders of the ion channel of the acetylcholine
      receptor of the neuromuscular junction. This is a case report of 25-years-old man
      with progressive ptosis and limitation of ocular movements since infancy,
      presented a 6-years history of worse of the external ophthalmoparesis and
      muscular weakness in the shoulders and hands. The motor nerve conduction studies
      after a supramaximal single stimulus disclosed a double compound muscle action
      potential (CMAP) that disappeared after a voluntary contraction of 30 seconds.
      Repetitive stimulation of facial and spinal accessory nerves showed a CMAP
      decrement greater than 10% with disappeared of the second potential. The patient
      received fluoxetine with mild improvement of muscular weakness, but persisted
      with: ptosis, limitation of ocular movements and repetitive CMAP in the motor
      nerve conduction study. The characteristic of disease are discussed.

PMID- 16791379
TI  - [Intermediary form of Foix-Chavany-Marie / Worster-Drought syndromes associated
      to involuntary movements: neuropsychological and phonoaudiological features].
AB  - The Foix-Chavany-Marie syndrome (FCMS) is characterized by apraxia of speech
      associated to bilateral central facio-linguo-velo-pharyngeal paralysis, with
      automatic-voluntary dissociation. In Worster-Drought Syndrome (WDS), dysarthria
      is remarkable. We report an 18-year-old female, with clinical and radiological
      findings of intermediary form of FCMS/WDS, and showing involuntary movements, an
      unusual fact.

PMID- 16791380
TI  - [Neurocysticercosis in a State of Piaui urban area: case report].
AB  - Neurocysticercosis is a serious public health problem that predominantly affects
      places with poor sanitary and hygiene conditions. The Piaui State is out of the
      neurocysticercosis map in Brazil but, as this study illustrates, it is just by
      lack of epidemiologic data. We demonstrate the presence of this pathology in the
      State of Piaui based on a case report of a 39 years old man, followed for 17
      months. The diagnosis was made by CT scan and the patient was treated with
      albendazol for 10 days. A new CT scan show absence of lesions. He needed to be
      treated again after a recurrence of clinical manifestations, 6 months after the
      first treatment, with the disappearance of the new lesions.

PMID- 16791381
TI  - [Fibrous dysplasia of the clivus: case report].
AB  - We describe the case of a 43 year-old woman with chronic headache and diplopia.
      The neuroradiologic exam showed volume increase and alteration in the bone
      density of the clivus. She was submitted to surgery and the anatomopathologic
      evidenced fibrous dysplasia. Other 14 of about fibrous dysplasia involving the
      clivus are related in the literature. We discuss clinical aspects, image exams,
      histology and treatment of this rare presentation of the disease.

PMID- 16791382
TI  - [Dural sinus thrombosis: case report].
AB  - We report the case of a 24 year-old pregnant woman, seen at the neurology service
      by presenting agitation, hallucinations, mental confusion, headache, vision loss,
      aphasia and seizures. The neuroradiologic exam was compatible with thrombosis in
      dural sinus and cortical veins. Treatment with abciximab was accomplished and the
      mechanical lysis of the thrombus was made obtaining restoration of cerebral vein
      flow. After the procedure, she presented frontal hematoma which was withdrawn
      surgically. We discuss this infrequent pathology in clinical picture,
      pathogenesis, image exams and therapeutics.

PMID- 16791383
TI  - [Intramedullary spinal cord metastasis from thyorid carcioma: case report].
AB  - We report a case of intramedullary spinal cord metastasis from thyroid cancer in
      a 70-year-old woman complaining for three months an intense cervical pain,
      without motor or sensitive deficits. Six months before the onset of symptoms, the
      patient underwent total thyroidectomy for a thyroid cancer. Magnetic resonance
      imaging with gadolinium enhancement showed an intramedullary spinal cord lesion.
      A partial resection of the medullar tumor was performed and the pathological
      findings showed an metastatic adenocarcinoma. Post operatively the patient
      developed a left crural monoplegia.

PMID- 16791386
TI  - [Autism and the pervasive developmental disorders].

PMID- 16791384
TI  - [Clinical and interventional revascularization in the acute ischemic stroke:
      national opinion].
AB  - The Brazilian Stroke Society constituted a committee composed by specialists from
      different areas of Brazil that emitted a viewpoint called "National Opinion,"
      considering the interventional procedures and thrombolysis in the treatment of
      the acute ischemic stroke. This study presents the conclusions of this committee.

PMID- 16791387
TI  - [Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative
      disorder and pervasive developmental disorder not otherwise specified].
AB  - The category "Pervasive Developmental Disorders" includes autistic disorder,
      Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a
      residual category, named pervasive developmental disorder not otherwise
      specified. In this review, Rett's syndrome and childhood disintegrative disorder,
      which are well-defined categories, will be discussed, as well as the not well
      defined categories that have been included in the Pervasive Developmental
      Disorder Not Otherwise Specified group. Different proposals of categorization
      have been created, some of which based on descriptive phenomenological approach,
      and others based upon other theoretical perspectives, such as neuropsychology.
      Current proposals are presented and discussed, followed by critical appraisals on
      the clinical advantages and disadvantages of these concepts.

PMID- 16791388
TI  - [Autism: neuroimaging].
AB  - Autism is a neurodevelopmental disorder with a range of clinical presentations.
      These presentations vary from mild to severe and are referred to as autism
      spectrum disorders. The most common clinical sign of autism spectrum disorders is
      social interaction impairment, which is associated with verbal and non-verbal
      communication deficits and stereotyped and repetitive behaviors. Thanks to recent
      brain imaging studies, scientists are getting a better idea of the neural
      circuits involved in autism spectrum disorders. Indeed, functional brain imaging,
      such as positron emission tomography, single foton emission tomography and
      functional MRI have opened a new perspective to study normal and pathological
      brain functioning. Three independent studies have found anatomical and rest
      functional temporal lobe abnormalities in autistic patients. These alterations
      are localized in the superior temporal sulcus bilaterally, an area which is
      critical for perception of key social stimuli. In addition, functional studies
      have shown hypoactivation of most areas implicated in social perception (face and
      voice perception) and social cognition (theory of mind). These data suggest an
      abnormal functioning of the social brain network in autism. The understanding of
      the functional alterations of this important mechanism may drive the elaboration
      of new and more adequate social re-educative strategies for autistic patients.

PMID- 16791389
TI  - [Autism: genetics].
AB  - Autism is a strongly genetic disorder, with an estimated heritability of greater
      than 90%. A combination of phenotypic heterogeneity and the likely involvement of
      multiple interacting loci have hampered efforts at gene discovery. As a
      consequence, the genetic etiology of the spectrum of autism related disorders
      remains largely unknown. Over the past several years, the convergence of rapidly
      advancing genomic technologies, the completion of the human genome project, and
      increasingly successful collaborative efforts to increase the number of patients
      available for study have led to the first solid clues to the biological origins
      of these disorders. This paper will review the literature to date summarizing the
      results of linkage, cytogenetic, and candidate gene studies with a focus on
      recent progress. In addition, promising avenues for future research are
      considered.

PMID- 16791390
TI  - [Autism and Asperger syndrome: an overview].
AB  - Autism and Asperger syndrome are diagnostic entities in a family of
      neurodevelopmental disorders disrupting fundamental processes of socialization,
      communication and learning, collectively known as pervasive developmental
      disorders. This group of conditions is among the most common developmental
      disorders, affecting 1 in every 200 or so individuals. They are also the most
      strongly genetically related among developmental disorders, with recurrence risks
      within sibships of the order of 2 to 15% if a broader definition of affectedness
      is adopted. Their early onset, symptom profile, and chronicity implicate
      fundamental biological mechanisms involved in social adaptation. Advances in
      their understanding are leading to a new social neuroscience perspective of
      normative socialization processes and specific disruptions thereof. These
      processes may lead to the emergence of the highly heterogeneous phenotypes
      associated with autism, the paradigmatic pervasive developmental disorder, and
      its variants. This overview focuses on the history, nosology, and the clinical
      and associated features of the two most well-known pervasive developmental
      disorders - autism and Asperger syndrome.

PMID- 16791391
TI  - [Autistic disorder: current psychopharmacological treatments and areas of
      interest for future developments].
AB  - Autistic disorder and the group of related conditions defined as pervasive
      developmental disorders are chronic neurodevelopmental disorders starting in
      early childhood and affecting a significant number of children and families.
      Although the causes and much of the pathophysiology of the disorder remain
      unknown, in recent years a number of available medication treatments have been
      identified as holding promise in alleviating some of the most disabling
      maladaptive behaviors, associated with pervasive developmental disorders. However
      these treatments do not address the core symptoms of the disease and oftentimes
      their side effects outweigh their benefits. Therefore there is substantial need
      for new medications that are safer and more effective in addressing the behavior
      symptoms of autism. The aim of this review is to highlight the available current
      pharmacotherapies and those emerging treatments with potential to enhance the
      treatment options of patients with pervasive developmental disorders.

PMID- 16791392
TI  - [Autism: psychoeducational intervention].
AB  - There is increasing recognition about the importance of taking into account both
      child and family needs when treating autism. However it has been a major debate
      about what intervention is the most appropriate. In this paper we will review the
      current literature on the different interventions that have been used in the
      treatment of autism with special attention to those that are empirically based.
      It is not our objective to discuss in detail any particular intervention. We
      intend to present an overview of both positive aspects and limitations of
      different interventions. The conclusion is that there is no single approach that
      is totally effective for all children the whole time. Instead, it is argued that
      families change their expectation and values regarding their children's treatment
      according to the child's development and the family context. In other words, a
      specific intervention that may work well in a certain period of time (e.g. pre
      school years) may not work so well in the following years (e.g. adolescence).
      Finally the importance of early identification and treatment of autism is
      stressed.

PMID- 16791394
TI  - Development of new therapies, including regeneration of the kidney, for chronic
      kidney diseases.
AB  - The increasing number of patients on chronic hemodialysis is a great problem in
      the field of nephrology in Japan and Western countries. Current therapies for
      chronic kidney diseases (CKDs) can retard the progression of renal failure, but
      cannot completely stop their progression to endstage renal failure (ESRD). Many
      researchers are now studying new therapeutic targets for CKDs, by various
      methods. Furthermore, because organ donation for kidney transplantation is very
      limited in Japan, research on kidney regeneration is an important issue for the
      therapy of ESRD. To regenerate the kidney, stem cells and growth factors for the
      kidney are being extensively studied, although the clinical application of the
      results of these studies has not yet taken place.

PMID- 16791393
TI  - Gene expression profiling analysis in nephrology: towards molecular definition of
      renal disease.
AB  - The increase in progressive kidney disease, resulting in a constantly rising
      prevalence of endstage renal disease (ESRD), urgently warrants the development of
      more effective strategies to diagnose, prevent, and intervene in renal disease.
      Histological information obtained by renal biopsies (RBx) is a cornerstone of the
      current management of kidney disease. Renal tissue can provide critical
      information on the disease process not available by nontissue-based approaches.
      However, insight gained by conventional histopathology remains limited and
      additional strategies to define renal disease on a molecular level are required.
      The sequencing of the human genome, together with recent advances in genome-wide
      profiling techniques, has provided the framework for a comprehensive analysis of
      renal disease-associated transcriptional programs. In this review, strategies to
      apply these technological advances towards the analysis of RBx will be described,
      with special emphasis on their potential impact on clinical management, but also
      on their inherent limitations. Finally, an outlook towards the emerging proteomic
      studies of renal disease will be given.

PMID- 16791395
TI  - Mechanism of iodide transport in the rabbit cortical collecting duct.
AB  - BACKGROUND: Pendrin, an anion exchanger known to participate in iodide transport
      in the apical membrane of follicular cells of the thyroid gland, has recently
      been shown to exist in the apical membrane of the beta- and gamma-intercalated
      (beta/gamma-IC) cells of the cortical collecting duct (CCD). We examined
      mechanisms of iodide transport in the CCD. METHODS: Rabbit CCD was perfused in
      vitro, and lumen-to-bath flux coefficients for both (125)I(-) (K(I (lb))) and
      (36)Cl(-) (K(Cl (lb))) were measured simultaneously. The intracellular pH (pHi)
      of beta/gamma-IC cells in the perfused CCD was measured by microscopic
      fluorometory, by loading 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein
      tetraacetoxy methylester (BCECF-AM), a fluorescent marker for pHi. The effects on
      pHi of the replacement of NaCl with Na cyclamate, NaI, or NaBr in the lumen or
      bath were observed. RESULTS: K(I (lb)) was comparable to or slightly higher than
      K(Cl (lb)). Both iodide and chloride in the lumen caused self- and cross
      inhibitions to both fluxes. The addition of 5-nitro-2-(-3-phenylpropylamino)
      benzoate (NPPB), a Cl(-) channel inhibitor, to the bath significantly reduced
      K(Cl (lb)), but not K(I (lb)). Replacement of luminal fluid NaCl with Na
      cyclamate, NaI, or NaBr caused alkalization of pHi, no change in pHi, and slight
      acidification of pHi, respectively. Replacement of bath NaCl with Na cyclamate,
      NaI, or NaBr caused alkalization, alkalization, and acidification of pHi,
      respectively. Luminal NaI prevented the acidification of pHi caused by bath Na
      cyclamate. CONCLUSIONS: The data are consistent with the model that iodide is
      transported via the Cl(-)/HCO(3) (-) exchanger in the apical membrane of
      beta/gamma-IC cells and exits the basolateral membrane via an electroneutral
      transporter that is distinct from the Cl(-) channel. We could not, however,
      identify which type of beta/gamma-IC cell was mainly responsible.

PMID- 16791396
TI  - Use of base in the treatment of acute severe organic acidosis by nephrologists
      and critical care physicians: results of an online survey.
AB  - BACKGROUND: Acute severe metabolic acidosis associated with lactic acidosis or
      ketoacidosis can have severe detrimental effects on organ function, and might
      contribute to mortality. A general consensus exists that elimination of the cause
      of the acidosis is essential for treatment, but there is controversy concerning
      the use of base for the treatment of these disorders. Some physicians advocate
      administration of base when the acidosis is severe to prevent a decrease in
      cardiac output, whereas others oppose administration of base even when the
      acidosis is severe given the potential compromise of cardiac function.
      Nephrologists and critical care specialists are often the physicians developing
      recommendations for the treatment of severe acid-base disorders. METHODS: A short
      online survey of 20 questions was developed to assess the approach to the
      treatment of acute metabolic acidosis of program directors of fellowship programs
      and experts from the specialties of critical care and nephrology. RESULTS:
      Although there was variability among individual physicians from both specialties,
      a larger percentage of nephrologists than critical care physicians queried
      recommended administration of base for the treatment of lactic acidosis (86% vs
      67%) and ketoacidosis (60% vs 28%). Also, critical care physicians in general
      used a lower level of blood pH when deciding when to initiate treatment. Of the
      physicians who gave base, most utilized sodium bicarbonate as the form of base
      given. CONCLUSIONS: The results of this survey indicate that the decisions
      whether to use base for the treatment of acute severe metabolic acidosis, and
      under which circumstances, vary among physicians, and indicate the need for
      further studies to develop evidence-based guidelines for therapy.

PMID- 16791397
TI  - The oxalate level in ultrafiltrate fluid collected from a dialyzer is useful for
      estimating the plasma oxalate level in hemodialysis patients.
AB  - BACKGROUND: Patients on chronic hemodialysis are likely to develop secondary
      hyperoxalemia. It is, however, difficult to measure plasma oxalate levels. To
      measure plasma oxalate levels, rapid plasma separation, deproteinization, and
      acidification are essential in preventing the formation of oxalate and the
      deposition of calcium oxalate within the test tube. The present study was
      undertaken to examine whether the oxalate level in dialyzer ultrafiltrate is
      potentially useful for estimating plasma oxalate levels. METHODS: In nine
      patients on chronic hemodialysis, the plasma, after deproteinization with a
      filter, and the ultrafiltrate from the dialyzer before hemodialysis were
      acidified to a pH level of less than 3, followed by the measurement of oxalate
      levels by ion chromatography. Also, oxalate levels were compared between
      acidified and non-acidified ultrafiltrates from the dialyzer. In the second part
      of the study, seven patients on chronic hemodialysis receiving erythropoietin
      therapy, in whom the ferritin level was more than 300 ng/ml and transferrin
      saturation was less than 25%, were intravenously administered ascorbic acid, 100
      mg, three times a week, after each dialysis session to facilitate the utilization
      of stored iron. This treatment was continued until the serum ferritin level
      decreased to a level below 300 ng/ml (for 3 months, at a maximum). The oxalate
      level in the dialyzer ultrafiltrate after this treatment was compared with that
      before treatment. RESULTS: The mean +/- SE oxalate level in the dialyzer
      ultrafiltrate was 45 +/- 6 micromol/l, essentially equal to the plasma oxalate
      level (46 +/- 7 micromol/l). The plasma oxalate level had a significant positive
      correlation with the dialyzer ultrafiltrate oxalate level (plasma oxalate level =
      0.99 x dialyzer ultrafiltrate oxalate level + 1.5; r = 0.95; P < 0.0001). The
      oxalate level in the acidified ultrafiltrate (45 +/- 6 micromol/l) did not differ
      significantly from that in the non-acidified ultrafiltrate (45 +/- 6 micromol/l).
      The mean +/- SE duration of ascorbic acid administration was 64 +/- 13 days. The
      hemoglobin level remained unchanged at 9.6 +/- 0.4 g/dl, whereas the serum iron
      level increased significantly, from 34 +/- 2 microg/dl to 43 +/- 4 microg/dl (P <
      0.05), and serum ferritin levels decreased significantly, from 645 +/- 219 ng/ml
      to 231 +/- 30 ng/ml after the treatment (P < 0.05). The oxalate level in the
      acidified ultrafiltrate showed no significant change after ascorbic acid
      administration (31 +/- 8 micromol/l vs 47 +/- 7 micromol/l). CONCLUSIONS: In
      patients on chronic hemodialysis, the oxalate level in acidified ultrafiltrate
      from the dialyzer was found to be useful for estimating the plasma level of non
      protein-bound oxalate. When administering ascorbic acid to hemodialysis patients,
      the plasma oxalate level can be monitored using this method.

PMID- 16791398
TI  - True hyponatremia secondary to intravenous immunoglobulin.
AB  - Hyponatremia is characterized as either "true hyponatremia," which represents a
      decrease in the Na(+) concentration in the water phase of plasma, or
      "pseudohyponatremia," which is due to an increased percentage of protein or lipid
      in plasma, with a normal plasma water Na(+) concentration ([Na(+)]).
      Pseudohyponatremia is a known complication of intravenous immunoglobulin (IVIG).
      Because IVIG has been reported to result in post-infusional hyperproteinemia,
      IVIG-induced hyponatremia has been attributed to pseudohyponatremia. In this case
      report, we demonstrate that IVIG therapy can result in true hyponatremia,
      resulting from sucrose-induced translocation of water from the intracellular
      compartment (ICF) to the extracellular compartment (ECF), as well as the infusion
      of a large volume of dilute fluid, in patients with an underlying defect in
      urinary free water excretion.

PMID- 16791399
TI  - Coexistence of three distinct adrenal tumors in the same adrenal gland in a
      patient with primary aldosteronism and preclinical Cushing's syndrome.
AB  - A 62-year-old woman was admitted to our hospital because of hypokalemia. Physical
      examination revealed no signs of excessive adrenocortical steroid production, as
      are found in Cushing's syndrome. Her plasma renin activity (PRA) was suppressed
      (0.10 ng/ml per h), and her serum aldosterone level was high (30.0 ng/dl). PRA
      was not increased after a renin-releasing test. Her plasma adrenocorticotropic
      hormone (ACTH) level was low (<5 pg/ml), but her serum cortisol level was normal
      (21.0 microg/dl). Administration of 8 mg dexamethasone did not suppress her
      plasma cortisol level. Finally, she was diagnosed with clinical primary
      aldosteronism associated with preclinical Cushing's syndrome. Magnetic resonance
      image revealed three sequential nodular masses (each 15 mm x 15 mm) in the right
      adrenal gland. A right adrenalectomy was performed by endoscopy. The three
      removed tumors appeared to have different characteristics. Microscopic
      examination revealed that the upper and lower tumors were adrenocortical
      adenomas, and the middle tumor was a black adenoma. Immunohistochemical staining
      for the enzymes involved in cortisol biosynthesis suggested that the upper tumor
      secreted aldosterone, whereas either or both of the two other tumors secreted
      cortisol. Surprisingly, at 33 years of age, she had been diagnosed with Cushing's
      syndrome, due to a cortisol-producing adrenocortical adenoma, and she had
      received a left adrenalectomy. Clinically and pathophysiologically, this was a
      very rare case.

PMID- 16791400
TI  - Pseudoaldosteronism due to the concurrent use of two herbal medicines containing
      glycyrrhizin: interaction of glycyrrhizin with angiotensin-converting enzyme
      inhibitor.
AB  - A 77-year-old man with a history of hypertension and hyperuricemia was admitted
      to our hospital complaining of limb weakness, persistent constipation, and
      worsening hypertension. He had been taking a Chinese herbal remedy for allergic
      rhinitis for the past 10 years, together with an angiotensin-converting enzyme
      inhibitor (ACE-I; enalapril, 20 mg daily). After the dosage of enalapril had been
      reduced to 10 mg daily about 1(1/2) years before the current admission, he had
      developed persistent constipation. Therefore, he had started taking another
      traditional Chinese herbal remedy, a laxative, for the constipation, about 4
      months prior to this hospitalization. Laboratory data on admission demonstrated
      marked metabolic alkalosis with severe hypokalemia associated with urinary
      wasting of potassium and chloride. A diagnosis of pseudoaldosteronism was made
      based upon his past history of exposure to various traditional Chinese medicines
      containing glycyrrhizin. Discontinuation of the Chinese remedies and
      supplementation of potassium successfully normalized the electrolyte imbalance
      and relieved all symptoms within a short time. The present case describes the
      occurrence of pseudoaldosteronism induced by a patient taking two traditional
      Chinese herbs, both containing glycyrrhizin, resulting in an overdose of this
      causative chemical agent. The development of pseudoaldosteronism appeared to be
      of particular interest with regard to the interaction of the renin-angiotensin
      aldosterone (RAA) system with glycyrrhizin, in which an ACE-I retarded the
      development of pseudoaldosteronism.

PMID- 16791401
TI  - Nephrotic syndrome and IgA nephropathy in polycystic kidney disease.
AB  - A 70-year-old man with polycystic kidney disease developed nephrotic syndrome,
      deteriorating to renal insufficiency. Histological examination revealed IgA
      nephropathy. With treatment of prednisolone, an angiotensin-converting enzyme
      inhibitor, and an angiotensin II receptor-blocker, his proteinuria markedly
      decreased and renal function was stabilized. This case supports the idea that
      renal biopsy is needed in patients with polycystic kidney disease with nephrotic
      range proteinuria, for appropriate treatment and prevention of renal failure.

PMID- 16791402
TI  - Nodular mesangial lesions, marked mesangiolysis, and fingerprint deposits of
      unknown origin in a patient with nephrotic syndrome: a unique combination of
      glomerular lesions.
AB  - A 46-year-old woman developed nephrotic syndrome at the age of 16 in 1973. On the
      basis of the histological findings of the first renal biopsy, she was diagnosed
      as having minimal change nephrotic syndrome. Initial treatment with steroid was
      effective, but she had several relapses during tapering of the daily dose of
      steroid. The second renal biopsy, performed in 1997, disclosed glomerular
      lobulation, mesangial proliferation, nodular mesangial lesions, and
      mesangiolysis. From 2001, the degree of proteinuria increased, with urinary
      protein being 5 g/day in January 2003, when a third renal biopsy was performed.
      On light microscopy, the glomerular lesions were similar to those observed in
      1997. Immunofluorescence microscopy revealed coarse granular stainings for IgG,
      IgA, IgM, kappa, lambda, and C3 in the mesangial area and along the capillary
      walls. On electron microscopy, fingerprint structures were observed in the
      mesangial and subendothelial deposits. There were no characteristic fibers in the
      nodular lesions. On the basis of clinical and laboratory findings in this
      patient, we excluded disease entities in which nodular mesangial lesions,
      mesangiolysis, and fingerprint deposits had been reported. To our knowledge, such
      a unique combination of glomerular lesions has not been described previously in
      the literature.

PMID- 16791404
TI  - A boy undergoing maintenance hemodialysis who developed mediastinal lymph node
      tuberculosis.
AB  - The incidence of tuberculosis (TBC) in patients undergoing maintenance
      hemodialysis is reported to be higher than that in the general population. We
      report an 8-year-old boy receiving such treatment for chronic renal failure who
      developed mediastinal lymph node TBC. He showed only intermittent fever,
      recurring every 2 weeks, with no other symptoms suggesting TBC. Although staining
      and culture of pharyngeal swab and gastric juice specimens failed to provide
      evidence of TBC, a lymph node biopsy specimen disclosed typical pathologic
      findings of tuberculoma, including caseating granulomas. Antituberculous therapy
      with isoniazid (INH), rifampicin, pyrazinamide, and ethambutol was given for 12
      months, resulting in complete resolution of the TBC, with no subsequent
      recurrence. To our knowledge, mediastinal lymph node localization of TBC is
      relatively rare, in a patient on maintenance hemodialysis, especially in a child.

PMID- 16791403
TI  - Tubulointerstitial immune complex nephritis in a patient with systemic lupus
      erythematosus: role of peritubular capillaritis with immune complex deposits in
      the pathogenesis of the tubulointerstitial nephritis.
AB  - Class IV-G (A/C) diffuse lupus nephritis and tubulointerstitial (TI) nephritis in
      a 31-year old woman was studied by light, immunofluorescence (IF), and electron
      microscopy (EM), to determine the pathogenesis of the TI lesions. The light
      microscopic findings showed peritubular capillaritis in the interstitium, with
      ruptures in the capillary structure, lysis of the surrounding tubular basement
      membrane (TBM), extravasated red blood cells (RBCs), the infiltration of
      neutrophils and mononuclear cells, and edema. The IF study revealed IgG, IgA,
      IgM, C1q, C3, and C4 depositions along the TBM, on the capillary walls, and in
      the interstitium proper. The EM study disclosed the deposition of immune
      complexes in the TBM, the capillary wall, and the interstitium proper. Based on
      these findings, the TI nephritis in this patient was considered to be due to
      peritubular capillaritis secondary to the immune complex depositions in the
      capillary wall of the interstitium.

PMID- 16791405
TI  - Recurrent metabolic alkalosis and elevated troponins after crack cocaine use in a
      hemodialysis patient.
AB  - When acid-base disorders have been described after cocaine use, they are usually
      metabolic acidosis. We report a case of recurrent crack cocaine use associated
      with severe metabolic alkalosis on two successive admissions, in a patient in
      renal failure on hemodialysis and with minimal urine output, despite no history
      of vomiting or alkali ingestion. The metabolic alkalosis did not recur after
      counseling and abstention from cocaine.

PMID- 16791406
TI  - Cystic beta2-microglobulin amyloidoma in a patient on long-term hemodialysis.
AB  - We report a patient with beta2 microglobulin amyloidosis (beta2M) in whom cystic
      tumors were seen in the bilateral axillary region. The patient was a 68-year-old
      woman who had been on hemodialysis for more than 20 years because of IgA
      nephropathy. Computed tomography-guided biopsy was performed to confirm the
      diagnosis. Congo red staining, beta2M immunohistochemistry, and electron
      microscopy examination of the biopsied sample showed extended beta2M deposits in
      the cystic tumor. beta2M-related amyloidosis in patients with long-term dialysis
      commonly presents as osteoarticular disease, although a soft-tissue pseudotumor,
      known as amyloidoma, has been reported. This is the first report in the English
      language literature of amyloidosis presenting as bilateral axillary cystic
      tumors.

PMID- 16791407
TI  - How many distinct tumors can exist simultaneously in a unilateral adrenal gland,
      and are they hormonally active or inactive?

PMID- 16791408
TI  - Why is acute post-streptococcal glomerulonephritis more common in the pediatric
      population?

PMID- 16791409
TI  - Subthalamic nucleus deep brain stimulation does not alter long-term heart rate
      variability in Parkinson's disease.
AB  - The power spectra of the heart rate variability frequency bands, analyzed from 24
      hour ECG recordings, did not change 12 months after bilateral subthalamic nucleus
      operation in 14 patients with Parkinson's disease.

PMID- 16791410
TI  - Phase I/II study of docetaxel, ifosfamide, and doxorubicin in advanced,
      recurrent, or metastatic soft tissue sarcoma (STS).
AB  - BACKGROUND: Based on reports of the efficacy of docetaxel (T) in STS, we
      undertook a phase I/II trial to determine the response rate (RR), dose-limiting
      toxicity (DLT), and maximum tolerated dose (MTD) of addition of T to doxorubicin
      (A) and ifosfamide (I) in advanced STS. METHODS: Patients with advanced,
      recurrent, or metastatic STS, without prior chemotherapy, were enrolled in a dose
      escalation trial. Dose levels: I-A 40 mg/m(2); I 4.0 gm/m(2); T 40 mg/m(2), II-A
      50; I 5.0; T 50, III-A 60; I 6.0; T 60, and IV-A 75; I 7.5; T 75. MTD was defined
      as the dose producing DLTs in >or=2 of 3-6 patients treated. RESULTS: 21 patients
      were accrued. Median age: 55 (28-78) years. HISTOLOGY: leiomyosarcoma 10, spindle
      cell sarcoma 3, synovial sarcoma 2, angiosarcoma 1, fibrous histiocytoma 1,
      epitheliod hemangio-endothelioma 1, and 3 not specified. MTD was level III (A 60,
      I 6.0, and T 60). DLT was myelosuppression. All grade 4 toxicities were
      hematologic. Patients received median 2 cycles (range 2-9). Eight patients (38%)
      achieved partial response (PR). PR occurred after six cycles in 5 patients. 18
      patients died. Median overall survival: 17 months (95% CI, 9.1-33.6 months).
      CONCLUSIONS: The recommended Phase II dose of this combination is level III: A 60
      mg/m(2), I 6.0 g/m(2), T 60 mg/m(2), with mesna and granulocyte-colony
      stimulating factor. The RR is similar to that of AI in other trials, but the
      survival is better than anticipated.

PMID- 16791411
TI  - A phase II study of ZD6474 (Zactima, a selective inhibitor of VEGFR and EGFR
      tyrosine kinase in patients with relapsed multiple myeloma--NCIC CTG IND.145.
AB  - Multiple myeloma is a disease in which angiogenesis is postulated to be a target
      for therapy. Based on this hypothesis, we conducted a phase II trial of ZD6474
      (Zactima; a VEGFR inhibitor) 100 mg p.o. daily in patients with relapsed multiple
      myeloma. The primary efficacy endpoint was objective response as assessed by
      reduction in M protein. There were 18 patients with a mean age of 64 years. One
      patient was ineligible and one was not evaluable. Overall, ZD6474 was well
      tolerated and pharmacokinetic testing demonstrated that adequate drug levels were
      achieved. The most common drug-related adverse events were nausea, vomiting,
      fatigue, rash, pruritus, headache, diarrhea, dizziness, and sensory neuropathy,
      all of which were Grade I-II in severity. There were no drug-related serious
      adverse events. Laboratory adverse events were infrequent: one patient had Grade
      III anemia, and there were no Grade III changes in biochemistry. No significant
      QTc interval changes were seen. There were no responses in M protein levels. In
      conclusion, ZD6474 was well tolerated at a dose of 100 mg per day and achieved
      plasma levels predicted to inhibit VEGF signaling. However, this was not
      reflected in clinical benefit since none of the patients had a reduction in M
      protein.

PMID- 16791413
TI  - Evolution of CPV-2 and implication for antigenic/genetic characterization.
AB  - A few amino acid differences in the viral protein VP2 account for important
      antigenic and biological changes among feline parvovirus (FPV), canine parvovirus
      (CPV-2) and CPV-2 variants 2a and 2b. Several pieces of evidence suggest that CPV
      2 is still evolving as additional amino acid changes occurred within the main
      antigenic regions of CPV-2 capsid, altering the antigenic profile of the virus
      and stressing the need for implementing the diagnostic assays.

PMID- 16791412
TI  - Characterization and phylogenetic analysis of Brazilian chicken anaemia virus.
AB  - Chicken anaemia virus (CAV) was detected by a Nested-PCR assay in field samples
      from different regions of Brazil. The 539 bp amplified fragments of vp1 gene from
      44 field samples were sequenced and 10 new nucleotide sequences of CAV were
      observed. These sequences were phylogenetically analysed by Mega2 using neighbour
      joining distance methods with 1000 bootstrap replications. Phylogenetic analysis
      did not show correlation between CAV pathology pattern and genetic groups. The 10
      nucleotide sequences of the Brazilian samples were also analysed together with 30
      sequences of CAV strains previously described from other countries. The genetic
      variability observed was not related to the geographical distribution. Amino acid
      substitutions were detected at 9 positions of the Brazilian sequences and two of
      them had not been observed before, (65)R replacing the Q residue and (98)F
      replacing Y residue.

PMID- 16791414
TI  - Optimization of codon usage of poxvirus genes allows for improved transient
      expression in mammalian cells.
AB  - Transient expression of viral genes from certain poxviruses in uninfected
      mammalian cells can sometimes be unexpectedly inefficient. The reasons for poor
      expression levels can be due to a number of features of the gene cassette, such
      as cryptic splice sites, polymerase II termination sequences or motifs that lead
      to mRNA instability. Here we suggest that in some cases the problem of low
      protein expression in transfected mammalian cells may be due to inefficient codon
      usage. We have observed that for many poxvirus genes from the yatapoxvirus genus
      this deficiency can be overcome by synthesis of the gene with codon sequences
      optimized for expression in primate cells. This led us to examine colon usage
      across 2-dozen sequenced members of the Poxviridae. We conclude that codon usage
      is surprisingly divergent across the different Poxviridae genera but is much more
      conserved within a single genus. Thus, Poxviridae genera can be divided into
      distinct groups based on their observed codon bias. When viewed in this context,
      successful transient expression of transfected poxvirus genes in uninfected
      mammalian cells can be more accurately predicted based on codon bias. As a
      corollary, for specific poxvirus genes with less favorable codon usage, codon
      optimization can result in profoundly increased transient expression levels
      following transfection of uninfected mammalian cell lines.

PMID- 16791415
TI  - Secreted expression and purification of dengue 2 virus full-length nonstructural
      glycoprotein NS1 in Pichia pastoris.
AB  - The dengue 2 virus (DEN-2) RNA (NGC strain) was used as a substrate to produce
      DNA clones of the full-length NS1 genes via reverse transcriptase synthesis of
      cDNA followed by polymerase chain reaction amplification of the NS1 region.
      Products were cloned into pPICZalphaB vector for sequencing and into Pichia
      pastoris for expression. A recombinant protein with a molecular size of
      approximately 80 KDa was secreted into the supernatant from the yeast cells when
      induced with methanol. The expressed protein was able to bind with mouse
      polyclonal antibody or NS1-specific monoclonal antibody of dengue 2 virus.
      Purified NS1-poly(His)-tagged fusion protein was obtained from the expressed
      product by passing through a metal-chelating affinity chromatographic (MCAC)
      column. The study also verified that our purified rNS1 protein retained its
      antigenicity. High-level production of the rNS1 protein up to 70 mg/l indicates
      that P. pastoris is an efficient expression system for dengue virus full-length
      NS1 glycoprotein.

PMID- 16791416
TI  - Molecular characterization of a partitivirus from Ophiostoma himal-ulmi.
AB  - The complete nucleotide sequences of two double-stranded (ds) RNA molecules, S1
      (1,744 bp) and S2 (1,567 bp), isolated from an isolate HP62 of the Himalayan
      Dutch elm disease fungus, Ophiostoma himal-ulmi, were determined. RNA S1 had the
      potential to encode a protein, P1, of 539 amino acids (62.7 kDa), which contained
      sequence motifs characteristic of RNA-dependent RNA polymerases (RdRps). A
      database search showed that P1 was closely related to RdRps of members of the
      genus Partitivirus in the family Partitiviridae. RNA S2 had the potential to
      encode a protein, P2, of 430 amino acids (46.3 kDa), which was related to capsid
      proteins of members of the genus Partitivirus. Virus particles isolated from
      isolate HP62 were shown to be isometric with a diameter of 30 nm, and to contain
      dsRNAs S1 and S2 and a single capsid protein of 46 kDa. N-terminal sequencing of
      tryptic peptides derived from the capsid protein proved unequivocally that it is
      encoded by RNA S2 and corresponds to protein P2. It is concluded that O. himal
      ulmi isolate HP62 contains a new member of the genus Partitivirus, which is
      designated Ophiostoma partitivirus 1. A phylogenetic tree of RdRps of members of
      the family Partitiviridae showed that there are least two RdRp lineages of
      viruses currently classified in the genus Partitivirus. One of these lineages
      contained viruses with fungal hosts and viruses with plant hosts, raising the
      possibility of horizontal transmission of partitiviruses between plants and
      fungi. The partitivirus RdRp and capsid proteins appear to have evolved in
      parallel with the capsid proteins evolving much faster than the RdRps.

PMID- 16791417
TI  - Sequence of RNA-dependent RNA polymerase genes provides evidence for three more
      distinct mitoviruses in Ophiostoma novo-ulmi isolate Ld.
AB  - Three of the twelve double-stranded (ds) RNAs, dsRNAs 1a, 1b and 3b, which are
      located in the mitochondria of a diseased isolate, Ld, of the Dutch elm disease
      fungus, Ophiostoma novo-ulmi have been cDNA cloned and sequenced. Examination of
      the sequences of the RdRp genes predicted from the nucleotide sequences of the
      three dsRNAs suggest that they constitute the genome of three new mitoviruses.

PMID- 16791418
TI  - Bidens mosaic virus is a member of the Potato virus Y species.
AB  - The nucleotide sequence of the genomic 3' terminal region (1,702 bases) of two
      Brazilian Bidens mosaic virus isolates (BiMV: BiMV-p and BiMV-b) was determined.
      BiMV-p and BiMV-b share 98% nucleotide sequence identity, and are most closely
      related to members of the potyvirus species: Sunflower chlorotic mottle virus (an
      isolate of Potato virus Y) and Potato virus Y. BiMV-p shares 88% capsid protein
      amino acid identity and 77% 3'UTR nucleotide sequence identity with SuCMoV an
      isolate of Sunflower chlorotic mottle virus. Phylogenetic analyses suggest the
      close evolutionary relationship of BiMV, SuCMoV and Potato virus Y (PVY), members
      of the PVY species. According to the analyses of capsid protein and 3'UTR
      sequences BiMV isolates must be regarded as a strain of Potato virus Y species,
      but their differences in host reactions and the phylogenetic distance suggest
      that they would be most likely better placed in a taxon between species and
      strains.

PMID- 16791419
TI  - Murine gammaherpesvirus (MHV) MK3 gene sequence diversity among 72, 4556, and 68
      strains.
AB  - Murid herpesvirus 4 (MuHV-4) currently serves as a model for study of human gamma
      herpesvirus pathogenesis. It codes for MK3 protein that similarly as K5 protein
      of Kaposi's sarcoma-associated herpesvirus are members of a family of
      structurally related viral immune evasion molecules possessing RING-CH finger
      domain with ubiquitin ligase activity. Murine herpesvirus 72 (MHV-72) isolated
      from the same species of free-living small rodent is considered as closely
      related to Murine herpesvirus 68 (MHV-68). Studies on MHV-72, identified
      dissimilarity from MHV-68 in the sequence of glycoprotein 150 [K. Macakova, J.
      Matis, I. Rezuchova, O. Kudela, H. Raslova, M. Kudelova, Virus Genes 26, 89-95
      (2003)]. Murine herpesvirus 4556 (MHV-4556) is relatively new, till now,
      uncharacterised strain isolated from different murid species Apodemus
      flavicollis. We have therefore sequenced the MK3 gene of MHW-72 as well as of MHV
      4556 to find out the evidence of their difference from that of MHV-68. We show
      here the unique nucleotide mutation in MHV-72 MK3 gene changing the codon at C
      end of MK3 protein that was earlier predicted to function in interaction with
      TAP1/2. Furthermore, one from two nucleotide mutations found for MHV-4556 MK3
      gene changed the codon that is localized at N-terminus of MK3 protein. MHV-4556
      specific mutation was found within MK3 RING-CH finger domain known to be
      necessary for the ubiquitination of MHC class I proteins. Moreover, the latter
      established the new restriction site specific for MHV-4556.

PMID- 16791420
TI  - The intraleader AUG nucleotide sequence context is important for equine arteritis
      virus replication.
AB  - The 5(-terminal leader sequence of the equine arteritis virus (EAV) genome
      contains an open reading frame (ORF) with an AUG codon in a suboptimal context
      for initiation of protein synthesis. To investigate the significance of this
      intraleader ORF (ILO), an expression plasmid was generated carrying a DNA copy of
      the subgenomic mRNA7 behind a T7 promoter. Capped RNA transcribed from this
      construct was shown to direct, in an in vitro translation system, the synthesis
      of leader peptide as well as N protein. Site-directed mutations aimed to either
      optimize or weaken the sequence context of the ILO start codon affected leader
      peptide synthesis as predicted; no peptide was detected when the initiation codon
      was incapacitated. Translation of the downstream N gene was inversely affected by
      leader peptide production, consistent with a ribosomal leaky scanning mechanism.
      To investigate the role of the leader peptide in the EAV replication life cycle
      we generated, using an infectious EAV cDNA clone, two mutant viruses in one of
      which the ILO start codon was in an optimal Kozak context for translation
      initiation while in the other the codon was again incapacitated. Surprisingly,
      both mutant viruses were equally viable and exhibited similar phenotypes in BHK
      21 cells. However, their replication kinetics and viral yields were reduced
      relative to that of the wild-type parental virus, as were their plaque sizes.
      Importantly, the mutations introduced into the viruses appeared to be rapidly and
      precisely repaired upon passaging. Already after one viral passage a significant
      fraction of the viruses had regained the wild-type sequence as well as its
      phenotype. The results demonstrate that EAV replication is not dependent on the
      synthesis of the intraleader peptide. Rather, the leader peptide does not seem to
      have any function in the EAV life cycle. As we discuss, the available data
      indicate that the ILO 5( nucleotide sequence per se, not its functioning in
      translation initiation, is of critical importance for EAV replication.

PMID- 16791421
TI  - Inhibition of Japanese encephalitis virus NS1 protein expression in cell by small
      interfering RNAs.
AB  - Japanese encephalitis virus (JEV), a serious mosquitoborne flavivirus, causes an
      acute infection of the central system resulting in encephalitis of humans and
      many kinds of animals. A high proportion of the survivors exhibit neurogical and
      psychiatric sequelae. NS1 is one of important non-structural proteins, which was
      found to be associated with viral RNA replication. To inhibit NS1 expression,
      four small interfering RNAs (siRNAs) expression plasmids (pS-NS1A, pS-NS1B, pS
      NS1C and pS-NS1D) were generated to target four different coding regions of the
      NS1 gene, and were separately co-transfected into Vero cells with an NS1-EGFP
      fusion expression plasmid pNS1-EGFP. NS1 expression was evaluated by fluorescence
      microscope, flow cytometry assay, Western blot and RT-PCR. The results revealed
      that pS-NS1B, pS-NS1C and pS-NS1D could effectively and specifically inhibit NS1
      expression in Vero cells. Our data suggested that these siRNAs could be used to
      inhibit JEV replication by silencing NS1 protein expression in further study.

PMID- 16791422
TI  - Genetic variability of hepatitis B virus isolates in Poland.
AB  - There is very limited knowledge about the genetic variability of HBV strains
      circulating in the population of Polish chronically infected HBV patients. The
      aim of this study was to analyse the phylogenetic relatedness and polymorphism in
      some functional domains of HBV genome among chronically infected patients from
      northern Poland. Fifty-one serum samples were included to analysis of HBV genomes
      due to the viral load sufficient for DNA preparation and sequencing. The
      sequences of the rt polymerase/S and preC/BCP regions of those isolates were
      analysed, compared to genome sequences of different variants of HBV from GenBank
      database and genetic relatedness of Polish genotypes to known reference strains
      was estimated. A phylogenetic tree of 41 analysed genotype A isolates as well as
      8 genotype D strains was constructed showing relationship to know reference
      strains. Two isolates, initially classified as genotype F turned to be related to
      genotype H, newly described genotype deriving from genotype F, a very rare
      genotype in Europe. HBV genotypes' distribution pattern in Poland and
      phylogenetic relatedness seems to be different from our Eastern neighbours. Due
      to the fact that Poland is still ethnically uniform country, it is interesting to
      explore molecular epidemiology of HBV infections in our population.

PMID- 16791423
TI  - The complete genomic sequence of strain ROS/HUVLV-100, a representative Russian
      Crimean Congo hemorrhagic fever virus strain.
AB  - The complete genomic sequence (minus primer-generated ends) of the laboratory
      adapted Crimean Congo hemorrhagic fever virus (CCHFV) strain ROS/HUVLV-100,
      isolated in 2003 from the blood of a deceased female from the Rostov region of
      southern European Russia, was determined by direct sequencing of overlapping
      reverse transcription/polymerase chain reaction amplified products. The size of
      the ROS/HUVLV-100 genome is 19.2 kilobases--individual genome segments are
      similar in size and sequence features to previously reported "Europe-1" group
      CCHFV strains. The low-passage ROS/HUVLV-100 strain is the first Russian Crimean
      Congo hemorrhagic fever virus isolate for which complete sequence information is
      available, and this work reports the first complete genomic CCHFV sequence
      determined from a single viral RNA preparation in the same laboratory.

PMID- 16791424
TI  - Sequence analysis of the left end of fowl adenovirus genomes.
AB  - Nucleotide sequence analysis of the left end of the genome of fowl adenoviruses
      (FAdV) representing species group C (FAdV-4 and -10), D (FAdV-2) and E (FAdV-8)
      were carried out, and the sequence data was compared to those of FAdV-1 (FAdV-A)
      and FAdV-9 (FAdV-D). The viruses were propagated in chicken hepatoma cell line
      for viral DNA isolation. Restriction endonuclease analysis was performed followed
      by hybridization with two DNA probes representing the left end of FAdV-9. The
      identified fragments were sequenced, and the generated data were compared with
      the GenBank database. Nucleotide sequence homology and amino acid sequence
      identities were high between members of the same species group, FAdV-2 and -9,
      and FAdV-4 and -10, whereas different degrees of variations were observed among
      all FAdVs. Gene arrangement and position of ORFs at the left end of FAdV genomes
      were largely conserved suggesting similar gene functions. All previously
      characterized left end ORFs in CELO virus and FAdV-9 were found in all analyzed
      FAdVs. However, ORF 1C was absent in FAdV-4 and -10, but additional ORFs, most
      likely corresponding to duplicates of ORF 14, were observed in these viruses.

PMID- 16791425
TI  - New simian beta retroviruses from rhesus monkeys (Macaca mulatta) and langurs
      (Semnopithecus entellus) from Rajasthan, India.
AB  - Natural infection of feral Indian rhesus monkeys (Macaca mulatta) by a new simian
      beta retrovirus, provisionally called simian retrovirus-7 (SRV-7) is described.
      The virus is capable of in vitro replication in primary human peripheral blood
      lymphocytes (PBL) and B and T cell lines. We have earlier reported a novel SRV,
      SRV-6 from Indian langurs (Semnopithecus entellus). Additional sequence analyses
      from gp20 transmembrane (TM) env genes of SRV-6 and SRV-7 place them in a
      separate cluster, related to but distinct from known exogenous SRVs and also
      close to the simian endogenous beta retrovirus, (SERV) from African baboon.
      Phylogenetic analyses of pol gene of SRV-7 place it closer to SERV when the stop
      codons of the SERV genes are removed. On the other hand, additional sequence data
      from gp70, surface glycoprotein (SU) region of the env gene of SRV-6 suggest it
      is more closely related to known exogenous SRVs, (SRV-1 to 3). It is also related
      to the endogenous langur virus, Po-1-Lu. We hypothesize that SRV-6 and SRV-7
      probably originated from a progenitor exogenous SRV which recombined with an
      endogenous SERV in the TM env and pol genes during evolution, based on the
      phylogenetic analyses.

PMID- 16791426
TI  - Characterization of an avian influenza virus of subtype H7N2 isolated from
      chickens in northern China.
AB  - An H7N2 avian influenza virus was isolated from chickens during routine
      surveillance in northern China in 2002. To understand the origin of this virus,
      we completely sequenced its genome. The PB1, PA, HA, and M genes of this virus
      were highly homologous with those of the wild bird virus A/Africa starling/Eng
      Q/983/79 (H7N1). The NP and NS genes were closely related to those of two other
      wild bird viruses isolated 30 years ago. The closest relatives of the PB2 and NA
      genes of the virus were those of the A/swine/Germany/2/81 (H1NI) and
      A/Leningrad/134/57 (H2N2), respectively. Animal inoculation tests showed that the
      virus cannot replicate efficiently in chickens. However, after intranasal
      inoculation, the virus induced 20% weight loss and replicated well in the lungs
      of mice. The virus was also recovered from the hearts and brains of the mice.
      These results suggest that the influenza virus isolated in chickens in northern
      China in 2002 originated in wild birds and may pose a threat for both avian
      species and mammalian hosts.

PMID- 16791427
TI  - Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and
      mammalian cells.
AB  - Pex19p exhibits a broad binding specificity for peroxisomal membrane proteins
      (PMPs), and is essential for the formation of functional peroxisomal membranes.
      Pex19p orthologues contain a C-terminal CAAX motif common to prenylated proteins.
      In addition, Saccharomyces cerevisiae and Chinese hamster Pex19p are at least
      partially farnesylated in vivo. Whether farnesylation of Pex19p plays an
      essential or merely ancillary role in peroxisome biogenesis is currently not
      clear. Here, we show that (i) nonfarnesylated and farnesylated human Pex19p
      display a similar affinity towards a select set of PMPs, (ii) a variant of Pex19p
      lacking a functional farnesylation motif is able to restore peroxisome biogenesis
      in Pex19p-deficient cells, and (iii) peroxisome protein import is not affected in
      yeast and mammalian cells defective in one of the enzymes involved in the
      farnesylation pathway. Summarized, these observations indicate that the CAAX box
      mediated processing steps of Pex19p are dispensable for peroxisome biogenesis in
      yeast and mammalian cells.

PMID- 16791428
TI  - Expansion of amino acid homo-sequences in proteins: insights into the role of
      amino acid homo-polymers and of the protein context in aggregation.
AB  - Expansion of amino acid homo-sequences, such as polyglutamines or polyalanines,
      in proteins has been directly implicated in various degenerative diseases through
      a mechanism of protein misfolding and aggregation. However, it is still unclear
      how the nature of the expansion and the protein context influence the tendency of
      a protein to aggregate. Here, we have addressed these questions using
      spinocerebellar ataxia type-3 (ATX3) protein, the best characterised of the
      polyglutamine proteins, chosen as a model system. Using a transfected mammalian
      cell line, we demonstrate that ATX3 aggregation is noticeably reduced by deletion
      or replacement of regions other than the polyglutamine tract. The nature of the
      amino acid homo-sequences also has a strong influence on aggregation. From our
      studies, we draw general conclusions on the effect of the protein architecture
      and of the amino acid homo-sequence on pathology.

PMID- 16791429
TI  - Unique gene structure and paralogy define the 7D-cadherin family.
AB  - Cadherins are Ca2+-dependent transmembrane glycoproteins crucial for cell-cell
      adhesion in vertebrates and invertebrates. Classification of this superfamily due
      to their phylogenetic relationship is currently restricted to three major
      subfamilies: classical, desmosomal and protocadherins. Here we report evidence
      for a common phylogenetic origin of the kidney-specific Ksp- (Cdh16) and the
      intestine-specific LI-cadherin (Cdh17). Both genes consist of 18 exons and the
      positions of their exon-intron boundaries as well as their intron phases are
      perfectly conserved. We found an extensive paralogy of more than 40 megabases in
      mammals as well as teleost fish species encompassing the Ksp- and LI-cadherin
      genes. A comparable paralogy was not detected for other cadherin gene loci. These
      findings suggest that the Ksp- and LI-cadherin genes originated by chromosomal
      duplication early during vertebrate evolution and support our assumption that
      both proteins are paralogues within a separate cadherin family that we have
      termed 7D-cadherins.

PMID- 16791430
TI  - Pure pineal germinomas: analysis of gender incidence.
AB  - OBJECTIVE: Pure pineal germinomas have been rarely reported in girls. Gender
      incidence and differences of pure pineal germinomas are not well known. The
      authors report a series of pure pineal germinoma and its gender characteristic is
      reviewed. METHODS AND RESULTS: Of a total of 50 germ cell tumors operated on
      between 1988 and 2004 we found 26 cases (median age at diagnosis, 12 years) of
      pineal germ cell tumors. Of these, 14 cases (male/female ratio: 13/1) were pure
      pineal germinomas, and 12 cases (male/female ratio: 12/0) were non-germinoma germ
      cell tumors. In pure pineal germinomas, the main clinical presentations were
      intracranial hypertension and cranial nerve dysfunction. Imaging studies
      disclosed a homogeneous type of tumor (n = 10) and associated hydrocephalus (n =
      6). Cases were managed with biopsy and subsequent radiation therapy and
      chemotherapy. After a follow up of 10 years, pure germinoma cases have no
      neurological deficits and tumor recurrence. The literature on gender incidence of
      pure pineal germinomas is analyzed and possible causes are discussed.
      CONCLUSIONS: Although rare, pure pineal germinoma can be found in female
      subjects. On the basis of the literature review, the male/female ratio in cases
      of pure pineal germinoma is between 5:1 and 22:1 (mean 14:1). In our series, the
      male/female ratio was 13:1.

PMID- 16791431
TI  - A model for foramen ovale puncture training: Technical note.
AB  - BACKGROUND: Trigeminal neuralgia is a common cause of facial pain, characterized
      by shock-like pain affecting one or more branches of the trigeminal nerve. When
      conservative treatment fails and microdecompression is not indicated,
      percutaneous procedures are helpful. This percutaneous approach is done by a
      puncture up to the Gasserian ganglion, through the foramen ovale. Although simple
      and safe, this puncture demands some expertise from neurosurgeons. For that, a
      partnership between neurosurgeons and bio-engineers has developed a model for
      foramen ovale puncture, allowing practice for residents and young neurosurgeons.
      METHOD: A model for foramen ovale puncture has been created by interposition of
      synthetic materials over a skull, simulating the human face. FINDINGS: This model
      has shown great similarity with that found in conventional surgeries, even upon
      repeated testing by experienced functional neurosurgeons and young residents.
      CONCLUSION: This model for foramen ovale puncture training has demonstrated
      valuable help for initial practicing of this common neurosurgical procedure,
      particularly in centers where there are not many cadavers available for training.

PMID- 16791432
TI  - Late bacterial granuloma at an intrathecal drug delivery catheter.
AB  - In the case reported, neurological complaints were pain and dysaesthesiae in the
      lower back and thigh, as well as paresis of the ileopsoas muscle. MRI of the
      lumbar spine showed an intradural-extramedullary mass at the level of L1
      homogeneously enhancing with gadolinium. This mass was situated at the tip of an
      intrathecal catheter implanted 11 years before for a morphine trial infusion as
      therapy for phantom pain after amputation of the right arm. Now, removal of the
      catheter was performed. Cultures of lumbar CSF and the catheter tip demonstrated
      coagulase negative staphylococcus. Antibiotic medication with cephalosporines was
      given for 6 weeks. After removal of the catheter, the patient was free of pain
      and he progressively regained full neurological function. Although most catheter
      associated granulomas reported so far were sterile in nature, bacterial infection
      should still be considered even years after catheter placement.

PMID- 16791433
TI  - ECG abnormalities in predicting secondary cerebral ischemia after subarachnoid
      haemorrhage.
AB  - BACKGROUND: Electrocardiographic (ECG) abnormalities frequently occur after
      subarachnoid haemorrhage (SAH), and have been linked with poor outcome. The
      pathogenesis behind this relation is unclear. We hypothesized that cardiac
      dysfunction may contribute to the development of delayed cerebral ischemia (DCI)
      and investigated if electrocardiographic repolarization abnormalities on
      admission, representing this cardiac dysfunction, are related to DCI. We also
      assessed the additional value of ECG characteristics to establish prognosticators
      for clinical outcome (WFNS, age and Hijdra score). METHOD: In a series of 121
      consecutive patients with aneurysmal SAH we related individual repolarization
      like ECG changes (ST and T-wave changes, QTc prolongation, a U-wave) to the
      occurrence of DCI by means of Cox proportional hazard modelling and to poor
      outcome (death or dependence) with logistic regression analysis. We used ROC
      curves to assess the additional prognostic value of the most important ECG
      characteristics to established prognosticators. FINDINGS: Only ST segment
      depression had a statistically significant relationship with the occurrence of
      DCI (HR 2.4 [95%CI 1.2-4.9]) in univariate analysis. In a similar analysis ST
      elevation (OR 4.9; [95%CI 0.99-24.0]), ST-depression (OR 10.6; [95%CI 2.3-48.8]),
      T-wave inversion (OR 2.5; [95%CI 1.1-5.5]) and ischemic like ECG abnormalities
      (OR 8.3; [95%CI 3.0-22.2]) were significantly related to poor outcome. In
      multivariate models with extension of these ECG characteristics for establishing
      prognosticators the AUC of the ROC improved from 0.81 to 0.84. CONCLUSIONS: ECG
      abnormalities did not contribute to the prediction of DCI and have limited value
      in prognosticating poor outcome. The occurrence of DCI is not the explanation of
      this relationship between ECG characteristics and outcome.

PMID- 16791434
TI  - Clinical and radiological results following cervical arthroplasty.
AB  - BACKGROUND: This was a retrospective study of clinical and radiological results
      of cervical arthroplasty using the Bryan cervical disc prosthesis to evaluate the
      efficacy of arthroplasty in clinical applications. METHODS: A total of 46
      patients underwent arthroplasty of a single level using the Bryan disc
      prosthesis. Clinical outcome was assessed using the visual analogue scale (VAS)
      and the neck disability index (NDI). All patients were evaluated using
      preoperative and postoperative static cervical spine radiographs to compare
      cervical sagittal balance. Dynamic cervical spine radiographs were used to
      compare movement at the level of the procedure, movement at the adjacent level
      and movement of the whole cervical spine. FINDINGS: With the exception of four
      patients with aggravated neck pain, the NDI and VAS scores decreased
      significantly in late follow-up evaluations. The range of movement of the whole
      cervical spine, the functional segmental unit, and the adjacent segments were
      preserved after arthroplasty. The sagittal alignment of the cervical spine showed
      kyphosis after surgery but restored lordosis at a later time. The postulated
      cause of kyphotic changes include "over-milling" at the dorsal endplate,
      inappropriate angle of disc insertion, structural absence of lordosis in the
      Bryan disc, removal of posterior longitudinal ligament, and pre-existing
      kyphosis. CONCLUSIONS: Arthroplasty using the Bryan disc appears to be safe and
      provided a favorable preliminary clinical and radiological outcome. Postoperative
      kyphosis can be prevented by understanding the biomechanical properties of the
      Bryan disc. Future studies will need to address the association between
      postoperative kyphosis, clinical outcome and adjacent segment disease.

PMID- 16791435
TI  - Quality of life after treatment for incidental, unruptured intracranial
      aneurysms.
AB  - BACKGROUND: Discovering an intracranial aneurysm may profoundly affect the
      patient's quality of life. Patients living with unruptured and untreated
      aneurysms often report symptoms of anxiety and depression. There are few trials
      studying the quality of life after treatment of unruptured intracranial
      aneurysms. We aimed to compare the quality of life and symptoms of anxiety or
      depression after endovascular coiling or open surgery clipping of unruptured
      intracranial aneurysms, in patients with no prior subarachnoid haemorrhage.
      METHOD: 73 living patients were included. 44 had undergone open surgery clipping
      and 31 had undergone endovascular coiling within the last 5.5 years. We
      registered a number of parameters from medical records and the patients' current
      quality of life was assessed by a questionnaire. 63 of 73 (86.3%) returned our
      questionnaire, which included the Norwegian version of SF-36 and the Hospital
      Anxiety and Depression Scale (HAD). FINDINGS: Many patients treated for
      unruptured intracranial aneurysms have a relatively low quality of life. The low
      scores indicate that the patients experience limitations in their ability to work
      or accomplish desired activities due to perceived physical or mental handicaps.
      There were no significant differences between the open surgery group and the
      endovascular group when comparing quality of life parameters after treatment. A
      subgroup analysis of patients with a favourable functional outcome also showed
      reduced quality of life without any differences in the two treatment groups.
      There were no signs of improvement in quality of life over time. CONCLUSION:
      Quality of life after treatment does not seem to be a strong argument for
      choosing one modality of treatment over the other in patients with unruptured
      intracranial aneurysms. There are no significant differences in the quality of
      life of patients successfully treated using endovascular technique and patients
      who underwent craniotomy and clipping. We speculate that the low quality of life
      scores are due to factors unrelated to the aneurysms. The scores possibly reflect
      characteristics of a patient group where incidental aneurysms are more frequently
      diagnosed while undergoing extensive imaging procedures due to unrelated
      symptoms.

PMID- 16791436
TI  - Spontaneous relapsing and recurring large multiloculated posterior fossa enteric
      cyst.
AB  - Intracranial enterogenous cyst is an uncommon entity. We report a case of
      enterogenous cyst of the posterior fossa situated posterolateral to the brain
      stem and extending into the left CP angle cistern. Patient had spontaneous
      regression and recurrence of the cyst. Clinical features and radiological
      findings are described. Near total excision of the cyst was carried out through
      the retro mastoid route. Patient made a good postoperative recovery.

PMID- 16791437
TI  - An endoscopically proven ventriculitis-type, cyst-like intraventricular primary
      lymphoma of the central nervous system.
AB  - Primary ventriculitis form of primary CNS lymphoma (PCNSL) is very rare and
      difficult to diagnose from radiological findings. A 55-year-woman presented with
      a cystic mass in the lateral ventricle without evidence of demonstrable malignant
      cells in the cerebrospinal fluid (CSF). The endoscopic biopsy showed a
      ventriculitis-like thin web on the surface of the ventricular wall around the
      foramen of Monro, resulting in obstruction. Pathological diagnosis was non
      Hodgkin's lymphoma, B cell type. This case suggests that PCNSL should be
      considered as a differential diagnosis for a cystic ventricular lesion even with
      no malignant cells in the CSF.

PMID- 16791438
TI  - The effect of an adenosine A1 receptor agonist in the treatment of experimental
      subarachnoid hemorrhage-induced cerebrovasospasm.
AB  - BACKGROUND: Adenosine is a potent vasodilator and an important modulator of
      cardiovascular function. It has been postulated that nitric oxide (NO) is
      involved in adenosine-induced vasodilation. This study was designed to examine
      the effect of an adenosine A1 agonist, N6-cyclopentyladenosine (CPA), in the
      prevention of subarachnoid haemorrhage (SAH)-induced vasospasm. Method.
      Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3 mL
      autogenous blood into the cisterna magna. Intraperitoneal injections of CPA
      (0.003 mg/kg), or vehicle were administered 5 min and 24 hours after induction of
      SAH. The degree of vasospasm was determined by averaging the cross sectional
      areas of the basilar artery 2 days after SAH. Expressions of endothelial nitric
      oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in basilar
      artery were evaluated. Findings. There were no significant differences among the
      control and treated groups in physiological parameters recorded before sacrifice.
      When compared with animals in the control group, cross-sectional area of basilar
      arteries areas in the SAH only, SAH plus vehicle and SAH plus CPA groups were
      reduced by 19% (p < 0.01), 22% (p < 0.01), and 9% (p = 0.133), respectively. The
      cross-sectional areas of the CPA-treated group differed significantly from those
      of the SAH only and SAH plus vehicle group (p < 0.05). Induction of iNOS-mRNA and
      protein in basilar artery by SAH was not significantly diminished by CPA. The SAH
      induced suppression of eNOS-mRNA and protein were relieved by CPA treatment.
      Conclusions. This is the first evidence to show an adenosine A1 receptor agonist
      is effective in partially preventing SAH-induced vasospasm without significant
      cardiovascular complications. The mechanisms of adenosine A1 receptor agonists in
      attenuating SAH-induced vasospasm may be, in part, related to preserve the normal
      eNOS expression after SAH. Inability in reversing the increased iNOS expression
      after SAH may lead to the incomplete anti-spastic effect of CPA.

PMID- 16791440
TI  - Gorham's disease of skull base and cervical spine--confusing picture in a two
      year old.
AB  - The unusual presentation of Gorham's disease of skull base and cervical spine in
      a two-year-old female child with radiological signs mimicking those of raised
      intracranial pressure is discussed. The differential diagnosis consists of skull
      base tumours, meningitis, osteomyelitis of the base of skull, congenital
      hydrocephalaus and congenital syndromes involving the skull base. Pathologically
      it can be very difficult to differentiate it from lymphangioma of the bone.
      Difficulty in establishing the diagnosis is discussed along with failure of
      radiotherapy and palmidronate therapy to cause arrest of the disease process and
      failure of surgery to provide stabilisation. We describe the course of the
      disease in this child over the period of last eight years. To the best of our
      knowledge this is the youngest case of Gorham's described so far.

PMID- 16791439
TI  - Primary CNS lymphoma in immunocompetent patients from 1989 to 2001: a
      retrospective analysis of 164 cases uniformly diagnosed by stereotactic biopsy.
AB  - BACKGROUND: We present outcome data of a cohort of 164 immunocompetent PCNSL
      patients uniformly diagnosed at a single center for stereotactic neurosurgery,
      and evaluate the acceptance and impact of combination radiotherapy (RT) and
      chemotherapy (CHT) with high-dose methotrexate (HD-MTX) over time. METHOD: We
      assessed choice of treatment and patient survival in a series of 164 PCNSL cases
      diagnosed from 1989 to 2001, and performed a re-evaluation of histopathology and
      pre-operative clinical data. FINDINGS: From 1989 to 1993, RT was the predominant
      therapy, and additional CHT did not improve survival. After 1994, the use of
      combination CHT/RT increased continuously, consistently contained MTX, and was
      associated with longer survival than RT only: median survival was 14 months after
      CHT/RT (2-year survival 35.7%) and 10 months (2-year survival 26.2%) after RT
      only (not significant). Overall median survival remained poor, increasing from
      six (1989-1993) to nine months (1994-2001) (p = 0.008). Survival was variable,
      with a few patients surviving >4 years after diagnosis in the CHT/RT as well as
      in the RT only group. CONCLUSIONS: Despite considerable improvement of PCNSL
      therapy, the overall benefit of combined CHT/RT versus RT only was lower than
      that expected from previous phase II clinical trials. The striking variability of
      survival in either treatment group may suggest a yet undefined biological
      heterogeneity of PCNSL, which may also include a more aggressive PCNSL subtype in
      the group of patients with rapidly progressive disease and not eligible for
      standard therapy.

PMID- 16791441
TI  - Copper induces conformational changes in the N-terminal part of cell-surface
      PrPC.
AB  - Prion diseases are caused by misfolding of the cellular prion protein, PrPC. In
      vitro studies have shown that PrP binds copper via the octarepeat region lying
      within the unstructured N-terminal segment of the protein, but the significance
      of copper in PrP metabolism remains unclear. Here, six specific antibodies
      recognizing different epitope regions of PrP were used to measure the effect of
      copper on the conformation of the molecule at the cell surface. Binding of an
      antibody, E149, to an epitope within the octarepeat domain of PrP is halved in
      the presence of copper, whereas binding of antibodies recognizing epitope motifs
      C-terminal to residue 90 of PrP remain relatively unaltered under equivalent
      conditions. These experiments strongly suggest that copper induces localized
      conformational change within the N-terminal portion of cell-surface PrPC.

PMID- 16791442
TI  - Papillomavirus virus-like particles as vehicles for the delivery of epitopes or
      genes.
AB  - Papillomaviruses (PVs) are simple double-strand DNA viruses whose virion shells
      are T = 7 icosahedrons and composed of major capsid protein L1 and minor capsid
      protein L2.L1 alone or together with L2 can self-assemble into virus-like
      particles (VLPs) when expressed in eukaryotic or prokaryotic expression systems.
      Although the VLPs lack the virus genome DNA, their morphological and
      immunological characteristics are very similar to those of nature
      papillomaviruses. PV VLP vaccination can induce high titers of neutralizing
      antibodies and can effectively protect animals or humans from PV infection.
      Moreover, PV VLPs have been good candidates for vehicles to deliver epitopes or
      genes to target cells. They are widely used in the fields of vaccine development,
      neutralizing antibody detection, basic virologic research on papillomaviruses,
      and human papillomavirus (HPV) screening. Besides the structural biology and
      immunological basis for PV VLPs used as vehicles to deliver epitopes or genes,
      this review details the latest findings on chimeric papillomavirus VLPs and
      papillomavirus pseudoviruses, which are two important forms of PV VLPs used to
      transfer epitopes or genes.

PMID- 16791444
TI  - Morbidly obese patients are hemodynamically stable during laparoscopic surgery: a
      thoracic bioimpedance study.
AB  - PURPOSE: Morbid obesity caries an increased risk of cardiovascular morbidity and
      might be associated with intraoperative hemodynamic instability. Based on
      clinical observation, we hypothesized that during laparoscopic surgery, morbidly
      obese patients behave hemodynamically similar to the nonobese patients and remain
      hemodynamically stable. METHODS: In a prospective trial, thirty nonobese and
      tthirty morbidly obese (BMI > or = 35 kg/m(2)) patients scheduled for elective
      laparoscopic surgery were assigned to receive standard balanced anesthesia. We
      aimed at equianesthetic levels by keeping the BIS (bispectral index) value
      between 40-50 throughout surgery. End-tidal isoflurane was measured every 5 min.
      Noninvasive hemodynamic measurements included cardiac index (CI), mean arterial
      pressure (MAP) and heart rate (HR), recorded every 5 min and at specific
      predetermined times. Systemic vascular resistance (SVR) was calculated. Episodes
      of MAP < or = 60 and MAP > or = 130 mmHg or HR < or = 50 and HR > or = 110 bpm
      occurring throughout surgery and requiring pharmacological intervention were
      considered main end-points. Additionally, hemodynamic variables were compared at
      specific time points and overall throughout surgery. Secondary end-points were CI
      and SVRI. RESULTS: Heart rate was higher in obese patients in head-up position
      (79 +/- 15 mmHg vs. 65 +/- 12 mmHg - P=0.011). SVR was higher in the nonobese
      group with head-up position (1978 +/- 665 dynes s cm(-5) vs. 1394 +/- 496 dynes s
      cm(-5) P=0.01). Mean overall intraoperative MAP, HR, CI and SVR were similar.
      There were no episodes of MAP < or = 60 and > or =130 mmHg or HR < or = 50 and >
      or =110 bpm in either of the groups. CONCLUSION: Our study confirmed our
      hypothesis that for the most periods of laparoscopic surgery, obese patients are
      hemodynamically as stable as their nonobese counterparts.

PMID- 16791445
TI  - Breast Cancer Axillary Surgery: Before, After, or None at All?

PMID- 16791446
TI  - Sentinel lymph node biopsy for local recurrence of breast cancer after breast
      conserving therapy.
AB  - BACKGROUND: Lymphatic mapping (LM) with sentinel lymph node (SLN) biopsy has
      revolutionized the surgical staging of primary breast cancer, but its utility and
      feasibility have not been established in patients with ipsilateral breast tumor
      recurrence (IBTR) after breast-conserving surgery (BCS) and radiation. METHODS:
      We reviewed our breast cancer database to identify all patients who underwent
      preoperative lymphoscintigraphy for IBTR and whose primary tumor had been managed
      by BCS, SLN biopsy and/or axillary node dissection, and adjuvant breast
      irradiation. RESULTS: Preoperative lymphoscintigraphy identified migration to the
      regional nodal drainage basins in 11 (73%) of 15 patients, as follows: 5
      ipsilateral axillary, 1 supraclavicular, 2 internal mammary, 2 interpectoral, and
      3 contralateral axillary. Two patients demonstrated drainage to two nodal basins.
      In four patients, no drainage was observed. Intraoperative LM with radioisotope
      plus blue dye identified at least 1 SLN in 11 of 14 patients, and histopathologic
      evaluation revealed metastasis in 3 patients (2 contralateral axillary and 1
      ipsilateral axillary). During preoperative lymphoscintigraphy, the radiocolloid
      migration time tended to be longer and the drainage pathways more variable than
      those associated with primary tumors. CONCLUSIONS: LM/SLN biopsy can be
      successfully performed in patients with IBTR after prior BCS, axillary surgical
      staging, and adjuvant radiation. This approach illustrates variations in the
      lymphatic drainage of recurrent breast tumors and may permit the identification
      of regional metastasis not noted with conventional imaging techniques.

PMID- 16791447
TI  - A laparoscopy-based score to predict surgical outcome in patients with advanced
      ovarian carcinoma: a pilot study.
AB  - BACKGROUND: Our objective was to set up a more objective quantitative laparoscopy
      based model in predicting the chances of optimal cytoreductive surgery in
      advanced ovarian cancer patients. METHODS: Sixty-four advanced ovarian cancer
      patients were submitted to both laparoscopy and standard longitudinal laparotomy
      sequentially, to define the chances of optimal debulking surgery (residual
      disease < or = 1 cm). Three patients could not be evaluated by laparoscopy
      because of the presence of multiple and tenacious adherences. Sensitivity,
      specificity, positive predictive value, negative predictive value, and overall
      accuracy were calculated for each laparoscopic parameter. On the basis of the
      statistical probability of each factor to predict surgical outcome, seven
      laparoscopic features were selected for inclusion in the final model. Each
      parameter was assigned a numerical score based on the strength of statistical
      association, and a total predictive index value was tabulated for each patient.
      Receiver operating characteristic curve analysis was used to assess the ability
      of the model to predict surgical outcome. RESULTS: After debulking surgery, 41
      (67.2%) of 61 patients were left with optimal residual disease. The presence of
      omental cake, peritoneal carcinosis, diaphragmatic carcinosis, mesenteric
      retraction, bowel and/or stomach infiltration, and liver metastases satisfied the
      basic inclusion criteria and were assigned a final predictive index value of 2.
      In the final model, a predictive index score > or = 8 identified patients
      undergoing suboptimal surgery with a specificity of 100%. The positive predictive
      value was 100%, and the negative predictive value was 70%. CONCLUSIONS: The
      reliability of laparoscopy in assessing the chance of optimal cytoreduction can
      be improved by using a simple scoring system.

PMID- 16791448
TI  - A phase II trial of isolated limb infusion with melphalan and dactinomycin for
      regional melanoma and soft tissue sarcoma of the extremity.
AB  - BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive technique of
      delivering regional chemotherapy in patients with advanced melanoma or soft
      tissue sarcoma of the limb. Reports from Australia of efficacy similar to that of
      isolated limb perfusion prompted us to conduct a phase II trial to evaluate the
      efficacy and safety of ILI. METHODS: Eligible patients had American Joint
      Committee on Cancer stage IIIB or IIIC melanoma or unresectable soft tissue
      sarcoma of the limb. Angiographic catheters were positioned just above the knee
      or elbow of the extremity. General anesthesia was performed, a proximal
      tourniquet was inflated, and a normothermic, low-flow, hypoxic infusion of
      melphalan and dactinomycin was circulated through the involved limb for 20
      minutes. The tumor response was assessed by using standard criteria at 3 months.
      Morbidity was determined in the hospital and at 2, 6, and 12 weeks. RESULTS:
      Twenty-five patients were accrued to the trial, and 32 ILIs were performed (8
      patients had 2 ILIs); 1 patient was not treated. Of the 22 assessable patients,
      11 (50%) had a significant response at 3 months: 23% of patients had a complete
      response, and 27% of patients had a partial response. The median duration of
      complete response was 1 year (range, 6-32 months). Morbidity was acceptable. Peak
      morbidity occurred at 2 weeks and was considered moderate in most patients. Limb
      edema and erythema were common. No patient developed compartment syndrome or
      required amputation. CONCLUSIONS: ILI is well tolerated. Half of the patients
      experienced a complete or partial response.

PMID- 16791449
TI  - Geographical variation in surveillance strategies after curative-intent surgery
      for upper aerodigestive tract cancer.
AB  - BACKGROUND: Analysis of geographical variation in utilization of medical
      resources is often used to identify regions of overutilization or
      underutilization. METHODS: We surveyed the membership of the American Head and
      Neck Society regarding their recommended frequency of office visits and 13
      imaging studies and blood tests for their patients after potentially curative
      therapy for upper aerodigestive tract cancers. RESULTS: Of the 1322 members
      surveyed, 610 (46%) responded: 420 responses (32%) were assessable. Responses
      were compared by US Census Region, Metropolitan Statistical Area, and managed
      care organization penetration rate. Overseas members (16% of assessable
      responses) comprised a separate category for the regional analysis. There were
      statistically significant variations in practice patterns among Census Regions
      for office visits, complete blood count, computed tomography of the head,
      sonography, and esophagoscopy. Non-US members recommended significantly more
      blood tests, imaging studies, and endoscopy than US members for routine cancer
      surveillance. Only the frequency of office visits differed significantly among
      Metropolitan Statistical Areas. Surprisingly, the penetration rate of managed
      care organizations had no significant effect on posttreatment surveillance
      intensity. CONCLUSIONS: This analysis indicates that only a small portion of the
      wide variation in observed follow-up practice patterns can be explained by
      geographical determinants.

PMID- 16791450
TI  - Selective blockade of vascular endothelial growth factor receptor 2 with an
      antibody against tumor-derived vascular endothelial growth factor controls the
      growth of human pancreatic adenocarcinoma xenografts.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF), a key regulator of
      angiogenesis, is critical for growth of human pancreatic adenocarcinoma.
      Preclinical studies demonstrate that blockade of VEGF activity can control the
      growth of pancreatic tumors in mice. In this study, we evaluated the efficacy of
      2C3, an antibody that inhibits VEGF receptor 2 activation by human VEGF, to
      inhibit the growth of human pancreatic adenocarcinoma in mice. METHODS: Human
      pancreatic cancer cell lines (MiaPaca-2, Panc-1, and Capan-1) were used to
      establish xenografts in nu/nu mice. The expression of VEGF and its receptors was
      determined in each cell line. Proliferation of tumor cells in vitro and tumor
      growth in vivo in the presence of 2C3 or a control antibody was evaluated. The
      effect of 2C3 on tumor weight, total vessel density, number of pericyte
      associated vessels, and tumor perfusion was determined, and the level of 2C3 in
      the serum of animals was measured by enzyme-linked immunosorbent assay. RESULTS:
      2C3 did not affect the proliferation of cells in culture. 2C3 was present and
      active in the serum of tumor-bearing animals treated with 2C3, and these animals
      showed a decrease in tumor burden compared with control-treated mice. Therapy
      with 2C3 resulted in reduced vascular function, measured by a decrease in vessel
      density and in the percentage of vessels associated with pericytes. Furthermore,
      tumors derived from Capan-1 cells demonstrated decreased perfusion after
      treatment with 2C3. CONCLUSIONS: Blockade of VEGF receptor 2 activation by tumor
      derived VEGF decreases tumor vessel function and growth of some human pancreatic
      adenocarcinoma cell lines in mice.

PMID- 16791451
TI  - Radiolocalized sentinel lymph node biopsy in squamous cell carcinoma of the oral
      cavity and analysis of various parameters.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy seems to be a method that solves the
      problem of neck management with oral squamous cell carcinoma. Using blue dye
      methods for detection of neck SLNs from the surface of the operative field seems
      difficult; therefore, we used radiolocalization alone to detect and extract
      sentinel nodes. Aside from the various histological and clinical parameters
      examined in this procedure, we also determined whether they had any clinical
      significance in relation to the detection of SLNs during the operation. METHODS:
      Enrolled subjects had preoperative clinical N0 stage squamous cell carcinoma of
      the oral cavity and had received an unfiltered (99m)Tc sulfur colloid peritumoral
      injection. Localization of the SLNs was performed by using lymphoscintigraphy and
      a handheld gamma probe. RESULTS: In total, 28 oral squamous cell carcinoma
      patients were included in this prospective study. Sixty-four SLNs in 27 patients
      were identified by this method. The identification rate was 96.4%. No false
      negative predictions of SLN were noted among any of the patients studied. The
      numbers of the SLNs found during the operation were larger in patients with
      positive findings than those with negative findings (P < .05 by the Mann-Whitney
      U-test). CONCLUSIONS: SLN radiolocalization provided an acceptable identification
      rate. The cases of positive findings for metastasis seemed to statistically have
      more SLNs than did those with negative findings, but more evidence is needed to
      prove this point. Therefore, SLN biopsies for extracting all possible high-risk
      nodes may be conducive for oral squamous cell carcinoma surgery.

PMID- 16791452
TI  - Radiofrequency ablation and laser ablation in the treatment of varicose veins.
AB  - Chronic venous insufficiency is a major medical disease in the United States.
      With a total population of 300 million, it is estimated that 25 million persons
      in this country alone have symptoms of this disease (1 in 12). Great saphenous
      vein reflux is the most common form of venous insufficiency in symptomatic
      patients and is most frequently responsible for varicose veins of the lower
      extremity. Therefore, therapy directed toward correcting superficial venous
      pathology is beneficial to many patients.

PMID- 16791453
TI  - The endowedge and kilt techniques to achieve additional juxtarenal seal during
      deployment of the Gore Excluder endoprosthesis.
AB  - The proximal 4 mm of the Gore Excluder endoprosthesis are scalloped. Our purpose
      is to describe our initial experience of a novel technique, referred to as the
      "endowedge," that takes advantage of this scalloped configuration in aneurysms
      with short proximal necks. The technique utilizes a balloon in the renal artery
      to aid alignment of a scallop and allow additional juxtarenal seal. A
      retrospective review of aneurysms treated with the endowedge technique at our
      institution was initiated. Renal balloons were placed via the brachial approach.
      Excluder endografts were deployed by flowering the first one or two rings, then
      advancing upward against the inflated balloon during completion of deployment. In
      patients with dumbbell-shaped morphology, an aortic cuff was deployed in the
      distal seal zone prior to the main body (kilt technique). Eight patients were
      identified, three of whom underwent an adjuvant kilt procedure. Average
      preoperative proximal neck length was 8.5 mm (range 6-12). Average additional
      juxtarenal seal was 2.3 mm. Mean follow-up was 5 months (range 2.5 weeks to 9
      months). There were no type I endoleaks. There were two type II endoleaks.
      Average aneurysm size decreased from 6.0 to 5.5 cm. No aneurysm has enlarged or
      ruptured. We conclude that the endowedge technique allows additional juxtarenal
      seal during endograft placement. Our early results suggest that this technique
      may allow for safe treatment of aneurysms with short necks.

PMID- 16791454
TI  - Survival and quality of life after arterial revascularization or major amputation
      for critical leg ischemia in Guadeloupe.
AB  - Functional outcome and survival in 253 patients treated for critical leg ischemia
      (CLI) in Guadeloupe (French West Indies) were analyzed. Analysis included
      calculation of quality-of-life score (QLS) from telephone survey data, with a
      median follow-up time of 42 months (range 12-109). A slight but significant
      benefit was observed in the 140 patients who underwent arterial reconstruction,
      with 76% autonomous ambulatory function, 51% independent residential status, and
      a QLS of 6.9 +/- 1.5 in comparison with the 113 patients who underwent
      amputation: 34%, 17%, and 5.1 +/- 2, respectively (p < 0.0001). Survival was
      comparable in the two groups. Inadequate medical follow-up that was either
      totally lacking or performed only in case of recurrent CLI as well as low rates
      of rehabilitation (50%) and prosthetic fitting (32%) in the amputation group
      highlight the existence of a double problem involving therapeutic compliance and
      vascular follow-up care/rehabilitation in Guadeloupe.

PMID- 16791455
TI  - Successful endovascular treatment of bleeding aortoenteric fistula: a case
      report.
AB  - Aortoenteric fistula (AEF) is an infrequent but disastrous complication of open
      abdominal aortic repair. Left untreated, it has a 100% fatality rate. The
      traditional approaches to the repair of secondary AEF (SAEF) are associated with
      average mortality rates of 21-59% and numerous major complications. Here, we
      report a case of acute gastrointestinal bleeding due to SAEF, successfully
      treated with endovascular stent graft repair. At 1-year follow-up, the patient
      was doing well without any signs of recurrent fistula. Endovascular treatment of
      AEF provides another treatment option that may be particularly valuable in
      patients whose comorbidities would preclude open repair.

PMID- 16791456
TI  - Correlation between the measurement of transverse diameter in the proximal neck
      on computed tomography and on aortography before endovascular treatment of
      infrarenal aortic aneurysm.
AB  - The aim of this study was to determine the correlation between the measurement of
      transverse diameter of the proximal neck on computed tomographic angiography
      (CTA) and graduated catheter aortography in patients who are candidates for
      endovascular graft placement in order to replace, if both measurements are
      equivalent, aortography for CTA alone. Preoperative dual-slice CTA and graduated
      catheter aortography were performed in 35 consecutive patients with infrarenal
      aortic aneurysm within 10 days. Transverse proximal neck diameters were measured
      on a true axial section on CTA reconstructions and on aortographic images, always
      6 mm distal from the most inferior main renal artery. Mean, median, and standard
      deviation were obtained and the measurements correlated for each patient using
      Pearson's correlation and linear regression analysis. A significant difference in
      proximal neck transverse diameter measurements was found between graduated
      catheter aortography and CTA in all cases. CTA values were a mean of 1.74 mm
      higher than aortography values. Pearson's correlation indicates a strong
      correlation between both techniques, and a regression equation determines the
      predictive value of aortography on the basis of CTA values. Estimation of the
      transverse diameter of the proximal neck on aortography on the basis of that
      obtained on CTA allows us to affirm that CTA could be used as the sole method for
      the preoperative selection of appropriate endograft size in patients with
      infrarenal aortic aneurysm.

PMID- 16791457
TI  - Colloids on free-standing smectic films.
AB  - We study the structure of a free-standing smectic-A film around a micron-size
      polystyrene colloid adsorbed onto the film. We find that a colloid or a cluster
      of colloids is surrounded by an optically distinct and radially decorated
      meniscus ending with a sharp edge. The observed strong and finite-range
      attraction between the adsorbed colloids is driven by the fusion of menisci. We
      interpret the structure of the smectic meniscus in terms of a model dominated by
      the surface free energy and we argue that the characteristic appearance of the
      meniscus is due to layer undulations.

PMID- 16791458
TI  - Collapse dynamics of smectic-A bubbles.
AB  - The collapse dynamics of smectic-A bubbles are analyzed experimentally and
      theoretically. Each bubble is expanded from a flat film stretched at the end of a
      hollow cylinder and deflated through a pressure release by means of a capillary
      tube. Its total collapse time can be varied between 0.1s and 20s by suitably
      choosing the length and the internal diameter of the capillary. This experiment
      allowed us to show that the collapse takes place in two steps: an initial one,
      which lasts a fraction of a second, where the meniscus destabilizes and fills up
      with focal conics, followed by a much longer period during which the bubble
      collapses and exchanges material with the meniscus. By measuring simultaneously
      the Laplace pressure and the internal pressure inside the bubble, we were able to
      fully characterize the shear-thinning behavior of the smectic phase within the
      meniscus. We emphasize that this method is generic and could be applied as well
      to other systems such as soap bubbles, on condition that inertial effects are
      negligible.

PMID- 16791459
TI  - Colloidal particles at a nematic-isotropic interface: effects of confinement.
AB  - When captured by a flat nematic-isotropic interface, colloidal particles can be
      dragged by it. As a result spatially periodic structures may appear, with the
      period depending on particle mass, size, and interface velocity (J.L. West, A.
      Glushchenko, G.X. Liao, Y. Reznikov, D. Andrienko, M.P. Allen, Phys. Rev. E 66,
      012702 (2002)). If liquid crystal is sandwiched between two substrates, the
      interface takes a wedge-like shape, accommodating the interface-substrate contact
      angle and minimizing the director distortions on its nematic side.
      Correspondingly, particles move along complex trajectories: they are first
      captured by the interface and then "glide" towards its vertex point. Our
      experiments quantify this scenario, and numerical minimization of the Landau-de
      Gennes free energy allows for a qualitative description of the interfacial
      structure and the drag force.

PMID- 16791460
TI  - Cutting Balloon angioplasty for the treatment of haemodyalisis vascular accesses:
      midterm results.
AB  - PURPOSE: The purpose of this study was to assess the effectiveness of Cutting
      Balloon angioplasty in the treatment of stenoses in haemodialysis arteriovenous
      accesses. MATERIALS AND METHODS: Over the past 2 years, we have observed 80
      patients with stenotic haemodialysis accesses; 24 of these (mean age 66.4 years,
      range 50-81) with 26 stenoses of 24 accesses (21 Cimino-Brescia fistulas and 3
      dialysis loops) were selected for Cutting Balloon angioplasty. In 11 cases, the
      Cutting Balloon device was used after failure to dilate the access with a high
      pressure balloon whereas in 15 cases (10 focal stenoses and 5 restenoses), it was
      used as a first choice. Two Cutting Balloon devices had a diameter of 8 mm, two
      of 7 mm, 11 of 6 mm, eight of 5 mm and one of 4 mm. The follow-up was performed
      by colour Doppler ultrasound (CDUS) and clinical assessment at 1, 3, 6, 12, 18
      and 24 months. RESULTS: In all patients, postprocedure angiography demonstrated
      immediate technical success. No periprocedural complications occurred. Follow-up
      examinations (range 3-24 months, mean 18.2 months) demonstrated patency of the
      vascular access and its good functioning during dialysis in 23/24 cases (95%).
      Only in one case did we observe a haemodynamically significant restenosis, which
      was treated again with Cutting Balloon angioplasty. CONCLUSIONS: Cutting Balloon
      angioplasty is safe and effective in the treatment of haemodialysis access
      stenosis, especially in cases of severe stenosis, with low restenosis rate both
      in the short and medium term.

PMID- 16791461
TI  - Stent graft in TIPS: technical and procedural aspects.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) is a nonoperative
      therapeutic option for the management of portal hypertension, variceal bleeding,
      recurrent ascites, Budd-Chiari syndrome. In view of the many issues surrounding
      the use of TIPS, in 1994 the US National Digestive Diseases Advisory Board
      convened a scientific conference to review the current data available and to
      establish the indications and controindications for this procedure. However there
      are still unsolved problems especially short primary patency of the shunt due to
      intimal hyperplasia, which causes a reduction of the shunt lumen thus favoring a
      return of the portal hypertension with recurrent variceal bleeding. Several study
      were performed in the last years to evaluate the efficacy of covered stent in
      order to reduce shunt disfunction secondary to intimal hyperplasia. PTFE seems to
      be more efficient in the prevention of restenoses. In our experience more then
      100 patients were treated with the Viatorr stent-graft. After a follow-up ranging
      from 1 to 50 months we reported a 1- year primary patency rate of 83.8%. However
      the use of the stentgraft is correlate with a high rate of hepatic hencefalopathy
      (46.6 %). In case of hepatic hencefalopathy refractory to the conventional
      medical therapy, TIPS reduction should be performed.

PMID- 16791462
TI  - Sonographic evaluation of clinically occult in-transit and satellite metastases
      from cutaneous malignant melanoma.
AB  - PURPOSE: Our purpose was to assess the potential of ultrasonography (US) in the
      detection of in-transit or satellite metastases. MATERIALS AND METHODS: Following
      a review of the relevant literature, we present the results of a retrospective
      study based on 2,000 malignant melanoma patients with complete case records. Of
      these, we selected 600 patients who had a thick melanoma (>1 mm) at presentation
      but were clinically free of in-transit or satellite melanoma metastases during
      follow-up. All patients underwent periodic clinical and imaging investigations,
      as well as US examination of the site of the surgical wound and surrounding soft
      tissues. RESULTS AND DISCUSSION: US raised the suspicion of in-transit or
      satellite metastases in 63 patients. A total of 95 lesions were identified.
      Average lesion diameter was 0.7 mm, and only four were larger than 1 cm. All
      suspected lesions were confirmed by surgery, follow-up or US-guided fine-needle
      aspiration (FNA) with 22-gauge needles using a freehand technique and exploiting
      the capillarity principle. In this series, there were apparently no false
      positive or false negative US results although inclusion criteria precluded
      correct evaluation of possible false negatives. Minimum lesion diameter allowing
      sonographic detection appears to be around 0.4 mm. US features of in-transit
      metastases have been well documented. They usually appear as solid lesions,
      hypoechoic relative to the surrounding subcutaneous fat and with relatively well
      defined and regular contours and good US transmission. Internal structure is
      fairly homogeneous, and sometimes millimetresized fluid areas can be appreciated
      inside. Larger metastatic lesions may exhibit internal vascular signals at power
      Doppler imaging. These findings in dermatological sonography are almost exclusive
      of metastases but may also be seen in glomangioma, which, however, has intense
      intralesional vascularity. US-guided FNA plays an important role in diagnosis of
      metastases from malignant melanoma. Of the 32 nodules that were cytologically
      sampled, a definitive or most probable diagnosis of metastasis was made for
      nodules with a mean diameter of 0.7 mm (minimum 0.5 mm). CONCLUSIONS: Sonography
      of soft tissues surrounding the original site of a malignant melanoma should be
      more widely used and associated with US-guided FNA biopsy.

PMID- 16791463
TI  - Assessment of pelvic endometriosis: correlation of US and MRI with laparoscopic
      findings.
AB  - PURPOSE: The purpose of this study was to evaluate the contribution of ultrasound
      (US) and magnetic resonance (MR) imaging in the diagnosis and local staging of
      endometriosis by comparing results with laparoscopic findings. MATERIALS AND
      METHODS: We evaluated 36 consecutive women with suspected or clinically diagnosed
      endometriosis. Thirty-two out of 36 patients met the following inclusion
      criteria: transabdominal and endocavitary (US) examination and MR imaging,
      followed by laparoscopy performed within 2 weeks. US and MR findings were
      classified based on location, number and morphology (small nodules, large
      nodules, laminar lesions, cystic lesions, complex lesions, adhesions, cul-de-sac
      obliteration). RESULTS: Laparoscopy, considered the gold standard, identified 143
      lesions in 32 patients. US detected 101 lesions, and MR detected 92 lesions,
      which were subsequently divided by morphologic appearance. Sensitivity and
      specificity of the two imaging techniques in the recognition of the different
      locations were 58% and 25%, respectively, for US and 56% and 50%, respectively,
      for MR imaging. Results of the two techniques in the different locations examined
      were similar, with the exception of lesions in the rectovaginal septum, which
      were better detected by US, and for adhesions and cul-de-sac obliteration, which
      were more easily detected by MR. CONCLUSIONS: Both US and MR are accurate in the
      diagnosis of endometriosis. There are no significant differences in staging of
      pelvic endometriosis between US and MR. US examination is the primary evaluation
      in cases of suspected disease and for the rectovaginal septum. MR examination is
      recommended for correct classification in doubtful cases and in cases of
      suspected extrapelvic lesions and adhesions.

PMID- 16791464
TI  - Diagnostic accuracy of chemical-shift MR imaging to differentiate between adrenal
      adenomas and non adenoma adrenal lesions.
AB  - PURPOSE: The objective of this study was to evaluate the diagnostic accuracy of
      chemical-shift (CS) magnetic resonance (MR) imaging in the differential diagnosis
      of adenoma and nonadenoma adrenal masses. MATERIALS AND METHODS: We enrolled 36
      patients (9 men, 27 women, mean age 51.3+14.4 years) with unilateral (n=31) or
      bilateral (n=5) adrenal masses incidentally discovered during imaging
      examinations [ultrasound (US), computed tomography (CT)] performed for other
      indications. A total of 41 adrenal lesions were evaluated (mean diameter 3.0+2.2
      cm). Histology (n=19), biopsy (n=3) or clinical-imaging follow-up (n=19)
      demonstrated 29 adenomas, five pheochromocytomas, three cysts and four
      carcinomas. MR imaging was performed using the following breath-hold sequences:
      T1-fast field echo (FFE) [repetition time (TR)/echo time (TE)=236/4.6 ms], T2
      turbo spin echo-single shot (TSE-SSh) (TR/TE=831/80 ms), T1-DUAL-FFE (TR=236,
      double TE=4.6/2.3 ms in phase and out of phase) and T1-FFE after gadolinium-DTPA
      (Gd). Axial and coronal imaging planes were used, with a slice thickness of 3-5
      mm. MR images were qualitatively assessed for signal intensity of the adrenal
      mass relative to the liver on T1, T2, CS and T1-Gd scans; diagnostic criteria for
      adenomas were isointensity or hypointensity on both T1 and T2 scans, out-of-phase
      CS signal loss and mild transient enhancement after Gd. RESULTS: Analysis of T1
      T2 signal intensity showed diagnostic accuracy, sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) of 80%, 72%,
      100%, 100% and 60%, respectively. In contrast, analysis of CS and T1-Gd signal
      intensity showed diagnostic accuracy, sensitivity, specificity, PPV and NPV for
      both sequences of 93%, 90% (p<0.05 vs. T1-T2 analysis), 100%, 100% and 80%
      (p<0.05 vs. T1-T2 analysis), respectively. CONCLUSIONS: CS MR imaging
      significantly improves characterization of adrenal masses compared with
      conventional T1-T2-weighted images, providing accuracy similar to that of the T1
      sequence after Gd. Therefore, the CS sequence is strongly recommended for MR
      study of adrenal masses, and its use might obviate the need for Gd
      administration.

PMID- 16791465
TI  - Gastrointestinal stromal tumour: spiral computed tomography features and
      pathologic correlation.
AB  - PURPOSE: Our purpose was to define the diagnostic accuracy of helical computed
      tomography (CT) in the identification, characterisation and evaluation of
      extension of gastrointestinal stromal tumours (GIST) through correlation with
      some pathological findings. MATERIALS AND METHODS: Between August 2000 and
      September 2004, we conducted a retrospective study of the abdominal CT of 15
      patients with histological diagnosis of GIST - that is, the immunopositivity for
      c-kit (CD117) - on a surgical specimen of the primary disease. We used a helical
      CT single-slice (Toshiba, Asteion; rotation time 0.75 s) in ten cases and helical
      CT multislice (Toshiba, Aquilion; 4 slices/rotation; rotation time 0.5 s) in five
      cases. In all cases, we used an organ-iodate nonionic contrast agent
      intravenously at a concentration of 350-400 mgI/ml. All cases studied the entire
      abdomen. Site, morphology and tumour size (smaller than 5 cm, 5-10 cm and larger
      than 10 cm) were considered parameters for tumour identification. Size, partial
      or total extraluminal tumour growth, homogeneous or inhomogeneous lesion
      enhancement and the eventual presence of calcifications were assumed to be
      criteria for characterisation of a GIST. Hepatic, peritoneal and/or lymph node
      metastases were considered parameters of intermediate or high malignancy. We
      correlated the results with some pathological features derived from the analysis
      of surgical tissue: site, morphology and tumour size, tissue components and risk
      of malignancy of GIST (on the basis of the 2002 Fletcher classification).
      RESULTS: We demonstrated one substantial concordance between radiological and
      pathological valuation of site, morphology, tumour size and absence of
      intralesional calcifications of GIST. Nine of ten GIST smaller than 5 cm, the two
      5-10 cm and the three larger than 10 cm presented extraluminal growth.
      Enhancement was inhomogeneous in five of ten lesions smaller than 5 cm and in all
      cases larger than 5 cm. At pathological analysis, in all cases of inhomogeneous
      enhancement, solid, hemorrhagic, necrotic and cystic areas were found. Of seven
      tumours of intermediate malignancy, six were smaller than 5 cm and only one
      larger than 10 cm; the two 5-10 cm were of high malignancy and all tumours
      superior of 10 cm were at intermediate or high malignancy. Of the two cases with
      metastases, one was of intermediate and one of high malignancy. In the other
      cases of intermediate or high malignancy, metastases were absent. CONCLUSIONS:
      The immunopositivity for c-kit is requisite for definitive diagnosis of GIST, but
      imaging, and particularly helical CT, has a primary role. In this study, CT is
      was reliable for tumour identification. All tumours larger than 5 cm presented
      extraluminal growth, inhomogeneous enhancement, absence of calcifications and
      lymph node metastases. Furthermore, the tumour larger than 5 cm showed
      extraluminal growth and inhomogeneous enhancement. Tumour size established with
      CT was not sufficient to determine the degree of malignancy. Metastases at the
      time of diagnosis were indicative of intermediate or high malignancy, but the
      absence of metastases did not allow classification of GIST in the group of low
      and very low risk of malignancy.

PMID- 16791466
TI  - Gastrointestinal stromal tumour: 40-row multislice computed tomography findings.
AB  - PURPOSE: The purpose of this study was to describe the findings and evaluate the
      role of multidetector (40-slice) computed tomography (MDCT) in the preoperative
      assessment of gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS:
      Thirteen patients with histologically proven GIST (size: 4-30 cm; mean: 9 cm)
      underwent 40-slice MDCT after the ingestion of 1,000 ml of water. Images were
      obtained before and 70 s after intravenous injection of 120 ml of iodinated
      contrast agent. Two experienced radiologists reviewed the CT findings to evaluate
      lesion site, size, margins, attenuation, growth pattern, enhancement pattern,
      ascites, lymphadenopathy, direct invasion to adjacent organs and distant
      metastasis. Multiplanar maximum intensity projection and three-dimensional (3D)
      reconstructions were also obtained. RESULTS: Seven out of 13 GISTs were located
      in the jejunumileum, 3/13 in the stomach, 2/13 in the rectum and in one case, the
      origin remained unknown. Eleven out of 13 were exophytic, and ten had well
      defined borders. Two out of 13 showed calcifications. Thirteen out of 13
      exhibited inhomogeneous enhancement due to areas of necrosis and cystic
      degeneration. Direct invasion to adjacent organs (n=3), ascites (n=3), and liver
      (n=1) and peritoneal (n=1) metastases were also detected. Bowel obstruction,
      vascular invasion and lymphadenopathy were never seen. CONCLUSIONS: MDCT allowed
      reliable preoperative assessment of GIST, providing useful clues for lesion
      characterisation.

PMID- 16791467
TI  - CT features of solitary fibrous tumour of the pleura: experience in 26 patients.
AB  - PURPOSE: The purpose of this study was to identify the typical computed
      tomography (CT) features of solitary fibrous tumours of the pleura (SFTP) and
      determine which findings would allow confirmation of the pleural origin or benign
      behaviour of the tumour. MATERIALS AND METHODS: Twenty-six preoperative CT
      studies of the chest (23 enhanced and 14 unenhanced) were retrospectively
      reviewed. RESULTS: Up to 50% of SFTP were larger than 10 cm. At unenhanced CT,
      they showed homogeneous attenuation in 5 cases (35.7%) and inhomogeneous
      attenuation in 9 (64.3%). At contrast-enhanced CT, they were inhomogeneous in 21
      cases (91.3%), with geographic pattern (61.9% of cases), serpiginous linear areas
      of enhancement (intralesional vessels) (23.8%), rounded (52.4%) or linear (33.3%)
      areas of low attenuation (necrosis). CONCLUSIONS: Depending on location, size and
      histological features, SFTP may produce a large spectrum of findings. Typical CT
      features of small SFTP were well-defined margins and smooth contours, homogeneous
      attenuation and right or obtuse angles with the pleura. Larger lesions were
      characterised by well-defined margins and lobulated contours, geographic pattern
      in enhanced CT scans, acute angles or smooth tapering margins with the pleura.

PMID- 16791468
TI  - Imaging of the patient with chronic bronchitis: an overview of old and new signs.
AB  - Up to now, neither chest radiograph nor high-resolution computed tomography
      (HRCT) has much to offer to the diagnosis of patients with chronic bronchitis
      (CB). A lot of HRCT findings can be observed, but they cannot be regarded as
      specific for pure CB. Their evaluation is often subjective, and measurements are
      poorly reproducible. In order to better characterise the HRCT features of CB,
      further efforts are warranted. The finding of bronchial wall thickening may even
      be considered nonsensitive as well as nonspecific. CB should not only be equated
      with narrowing of the airway since thickness of the bronchial wall may vary among
      different stages of development. Small pits can often be detected along the inner
      surfaces of the large bronchi in patients with CB using volumetric thin-section
      CT. Sometimes, multiple pits give rise to the accordion-like appearance that was
      described using bronchography. In our experience, they often occur in patients
      with long-lasting CB. A better comprehension of the large airways abnormalities
      is important because it is likely that the same pathophysiologic process that
      causes small-airway obstruction also takes place in larger airways, where it has
      less functional effect.

PMID- 16791469
TI  - Tomorrow's radiologist: what future?
AB  - Today's radiology is experiencing two major trends, one negative and one
      positive. The first is the so-called turf war, in other words, the progressive
      invasion of the imaging domain by other specialists such as cardiologists,
      urologists, gastroenterologists, gynaecologists etc. who are taking over various
      techniques from ultrasonography (US) to computed tomography (CT) to magnetic
      resonance imaging (MRI). In this process, they are aided by new technologies such
      as picture archiving and communication systems (PACS) and computed-aided
      diagnosis CAD and by radiology technologists who collaborate with them, replacing
      radiologists. The positive aspect is the outstanding technological evolution: the
      advent of molecular imaging, optical imaging, nanotechnologies, teleradiology and
      percutaneous gene therapy. While dramatically expanding the diagnostic
      possibilities down to the subcellular level, these techniques demand new forms of
      training in radiology and interdisciplinary cooperation. Tomorrow's radiologist
      will need to acquire appropriate clinical knowledge, restore contact with the
      patient to take on a prominent role in the diagnostic process, learn the basic
      sciences, foster a multidisciplinary approach and finally be able to use the
      Internet for learning and continuing education. Tomorrow's radiologists will
      survive if they learn to reinvent themselves.

PMID- 16791470
TI  - Proteomic identification of a two-component regulatory system in
      Pseudoalteromonas haloplanktis TAC125.
AB  - The capability of microorganisms to utilize different carbohydrates as energy
      source reflects the availability of these substrates in their habitat.
      Investigation of the proteins involved in carbohydrate usage, in parallel with
      analysis of their expression, is then likely to provide information on the
      interaction between microorganisms and their ecosystem. We analysed the growth
      behaviour of the marine Antarctic bacterium Pseudoalteromonas haloplanktis TAC125
      in the presence and in the absence of different carbon source. A marked increase
      in the optical density was detected when L: -malate was added to the growth
      medium. Bacterial proteins differently expressed in the presence of L: -malate
      were identified by proteomic profiling experiments. On the basis of their
      relative increase, six proteins were selected for further analyses. Among these,
      the expression of a putative outer membrane porin was demonstrated to be heavily
      induced by L: -malate. The presence of a functionally active two-component
      regulatory system very likely controlled by L: -malate was found in the upstream
      region of the porin gene. A non functional genomic porin mutant was then
      constructed showing a direct involvement of the protein in the uptake of L: 
      malate. To the best of our knowledge, the occurrence of such a regulatory system
      has never been reported in Pseudoalteromonads so far and might constitute a key
      step in the development of an effective inducible cold expression system.

PMID- 16791471
TI  - Expression of SOX9 and SOX10 in central neuroepithelial tumor.
AB  - The SOX group E transcription factors play an integral role in the specification
      and differentiation of astrocytes and oligodendrocytes. We have examined the
      pattern of expression for SOX9 and SOX10 in primary brain tumors by
      immunohistochemistry. Pediatric and adult high grade tumors display strong
      nuclear staining for both SOX9 and SOX10 (astrocytic, oligodendroglial and
      primitive neuroectodermal tumors). In comparison pediatric pilocytic astrocytoma
      express much less SOX9 and SOX10. Reactive astrogliosis is characterized by an
      increase of SOX9 only.

PMID- 16791472
TI  - Methamphetamine reward in mice as assessed by conditioned place preference test
      with Supermex sensors: effect of subchronic clorgyline pretreatment.
AB  - Recent studies in our laboratory have shown that methamphetamine (METH)-induced
      hyperlocomotion and behavioral sensitization in mice were inhibited by
      clorgyline, an irreversible monoamine oxidase inhibitor. In this study, the
      effect of clorgyline pretreatment on METH-induced rewarding effect was assessed
      by a conditioned place preference (CPP) test, using an apparatus developed with
      Supermex sensors (infrared pyroelectric sensors). Although intact male ICR mice
      showed significant CPP for METH (0.5 mg/kg, i.p.), pretreatment with subchronic
      clorgyline (0.1 and 10 mg/kg, s.c.) did not affect the magnitude of CPP. At a
      dose of 1 mg/kg, pretreatment of the mice with clorgyline showed a similar CPP
      index in both saline/saline and METH/saline pairing groups. During the
      conditioning session, the mice did not express behavioral sensitization to METH.
      Pretreatment with clorgyline (0.1, 1, and 10 mg/kg) decreased striatal apparent
      monoamine turnover in a dose-dependent manner. These results indicated that
      clorgyline pretreatment (0.1 and 10 mg/kg) did not influence the METH-induced
      rewarding effect in mice, although pretreatment of the mice with clorgyline at a
      dose of 1 mg/kg appeared to influence the CPP for METH.

PMID- 16791473
TI  - Measuring brain uptake and incorporation into brain phosphatidylinositol of
      plasma myo-[2H6]inositol in unanesthetized rats: an approach to estimate in vivo
      brain phosphatidylinositol turnover.
AB  - The in vivo rate of turnover of phosphatidylinositol (PtdIns) in brain is not
      known. In brain, certain receptor-mediated signal transduction involves
      metabolism of PtdIns and a method to measure its turnover in awake animals is
      useful in studying the effect of lithium and other therapeutic agents. In a
      method described here, rats were infused subcutaneously with myo-[2H6]inositol
      (Ins*) using an osmotic pump and, at 1 and 8 weeks, concentrations of free myo
      inositol (Ins) and Ins* in plasma and brain were measured by GC-MS (chemical
      ionization). Also, PtdIns and PtdIns* together in brain were isolated, and Ins
      and Ins* from their headgroups were released enzymatically and specific activity
      of incorporated inositol was measured. The specific activity of inositol reached
      a steady state in plasma within 1 week of infusion, but not in brain even at 8
      weeks. However, in brain, the specific activity of phosphatidylinositol was same
      as that of inositol at both time-points, suggestive of fast turnover of PtdIns.
      The animal experiment and the analytical methodology described here should be
      useful for measuring the rate of turnover of brain PtdIns in pathological and
      drug treatment conditions.

PMID- 16791474
TI  - Ascorbate transport and recycling by SH-SY5Y neuroblastoma cells: response to
      glutamate toxicity.
AB  - Neurons maintain relatively high intracellular concentrations of vitamin C, or
      ascorbic acid. In this work we studied the mechanisms by which neuronal cells in
      culture transport and maintain ascorbate, as well as how this system responds to
      oxidant stress induced by glutamate. Cultured SH-SY5Y neuroblastoma cells took up
      ascorbate, achieving steady-state intracellular concentrations of 6 mM and higher
      at extracellular concentrations of 200 microM and greater. This gradient was
      generated by relatively high affinity sodium-dependent ascorbate transport (Km of
      113 microM). Ascorbate was also recycled from dehydroascorbate, the reduction of
      which was dependent on GSH, but not on D-glucose. Glutamate in concentrations up
      to 2 mM caused an acute concentration-dependent efflux of ascorbate from the
      cells, which was prevented by the anion channel blocker 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid. Intracellular ascorbate did not
      affect radiolabeled glutamate uptake, showing absence of heteroexchange.

PMID- 16791475
TI  - Decreased alpha1-adrenergic receptor binding in the cerebral cortex and brain
      stem during pancreatic regeneration in rats.
AB  - The purpose of this study was to investigate the role of brain alpha1-adrenergic
      receptor binding in the rat model of pancreatic regeneration using 60-70%
      pancreatectomy. The alpha1-adrenergic receptors kinetics was studied in the
      cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7
      days pancreatectomised rats. Scatchard analysis with [3H]prazosin in cerebral
      cortex and brain stem showed a significant decrease (P < 0.01), (P < 0.05) in
      maximal binding (Bmax) with a significant decrease (P < 0.001), (P < 0.01) in the
      Kd in 72 h pancreatectomised rats compared with sham respectively. Competition
      analysis in cerebral cortex and brain stem showed a shift in affinity during
      pancreatic regeneration. The sympathetic activity was decreased as indicated by
      the significantly decreased norepinephrine level in the plasma (P < 0.001),
      cerebral cortex (P < 0.01) and brain stem (P < 0.001) of 72 h pancreatectomised
      rats compared to sham. Thus, from our results it is suggested that the central
      alpha1-adrenergic receptors have a functional role in the pancreatic regeneration
      mediated through the sympathetic pathway.

PMID- 16791476
TI  - E-cadherin immunohistochemical expression as a prognostic factor in infiltrating
      ductal carcinoma of the breast: a systematic review and meta-analysis.
AB  - PURPOSE: Multiple studies examining the relationship between loss of E-cadherin
      expression, a pivotal event for evolving metastatic behavior among epithelially
      derived cancers, and 5-year survival in infiltrating ductal breast carcinoma have
      yielded inconclusive and contradictory results. EXPERIMENTAL DESIGN: We conducted
      a systematic review of the PubMed database through August 2005 with no language
      restrictions to identify cohort studies that evaluated E-cadherin
      immunohistochemical expression as a prognostic marker for ductal breast
      carcinoma. 5-year all-cause mortality or 5-year breast cancer-specific mortality
      were the primary study outcomes. Meta-analysis was conducted using the REVMAN
      software and summary hazard ratios assuming both fixed effect and random effect
      models were calculated. RESULTS: Ten retrospective cohort studies were
      identified. Reduced or absent E-cadherin expression significantly increased the
      risk of all-cause mortality [combined HR = 1.55; 95% CI = 1.08-2.23] whereas a
      non-significant association was observed for breast cancer-specific mortality
      [combined HR = 0.70; 95% CI = 0.39-1.27]. We documented substantial inter-study
      heterogeneity with respect to all aspects of clinical data collection,
      immunohistochemical staining and interpretation as well as statistical modeling.
      These factors could not be formally analyzed but they challenge the robustness of
      our calculated summary estimates. CONCLUSIONS: Loss of E-cadherin expression may
      be an independent negative prognostic indicator for infiltrating ductal breast
      carcinoma and randomized, controlled studies evaluating this finding are
      justified. We encourage standardization of immunohistochemical techniques, data
      interpretation algorithms across laboratories and use of all-cause mortality to
      increase data compatibility and facilitate future efforts summarizing the utility
      of alternate prognostic markers in cancer.

PMID- 16791477
TI  - Rab11a differentially modulates epidermal growth factor-induced proliferation and
      motility in immortal breast cells.
AB  - The development of cancer prevention strategies depends on the elucidation of
      molecular pathways underlying oncogenesis. In a previous proteomic study of
      matched normal breast ducts and Ductal Carcinoma in Situ (DCIS), we identified
      overexpression of Rab11a in DCIS. Rab11a is not well studied in cancer, but is
      known to regulate the recycling of internalized cell surface proteins and
      receptors from the early endosome through the trans-Golgi network. Using
      immunohistochemistry, we confirmed our observation, noting increased Rab11a
      expression in 19 of 22 (86%) DCIS cases compared to matched normal breast
      epithelium. To study the function of Rab11a, immortal, nontumorigenic MCF10A
      breast cells were stimulated with ligands to the EGF receptor (EGFR) after
      transfection with empty vector (control), Rab11a, or a S25N dominant-negative
      (DN) Rab11a. Using an iodinated ligand:receptor recycling assay, transfection of
      Rab11a accelerated, while DN-Rab11a postponed EGFR recycling in vitro. The
      signaling and in vitro phenotypic consequences of Rab11a expression and function
      were studied. Transfection of DN-Rab11a increased Erk1/2 activation downstream of
      EGF, but exerted no effect on the Akt pathway. Expression of DN-Rab11a inhibited
      MCF10A proliferation by 50-60%, and also inhibited anchorage-dependent
      colonization. Notably, DN-Rab11a transfection increased motility toward EGFR
      ligands. The data provide a first demonstration that Rab11a modulates EGFR
      recycling, and promotes the proliferation but inhibits the motility of an
      immortal breast line, consistent with the DCIS phenotype.

PMID- 16791478
TI  - Association of GSTP1 CpG islands hypermethylation with poor prognosis in human
      breast cancers.
AB  - Glutathione S-transferase P1 (GSTP1) belongs to a family of phase II metabolic
      enzymes that can detoxify the carcinogens and cytotoxic drugs by conjugating them
      with glutathione. Relationship of GSTP1 CpG islands hypermethylation or GSTP1
      protein expression with clinicopathological characteristics of breast cancers was
      studied. The CpG islands hypermethylation status of GSTP1 gene was studied by
      methylation specific primer assay and GSTP1 expression was studied by
      immunohistochemistry in primary breast cancers. Of 174 breast tumors, 24 (14%)
      were found to have GSTP1 CpG islands hypermethylation. A significant association
      was found between GSTP1 CpG islands hypermethylation and large tumor size (P <
      0.01) or lymph node metastases (P < 0.05). Relapse-free survival (RFS) rates of
      patients with GSTP1 CpG islands hypermethylation were significantly poorer than
      those without it (5-year RFS rates; 60 vs. 86%, P < 0.01). Multivariate analysis
      showed that GSTP1 CpG islands hypermethylation status was a statistically
      significant prognostic factor being independent of other conventional prognostic
      factors. Immunohistochemical study showed that here was a significant association
      between GSTP1 CpG islands hypermethylation and loss of GSTP1 expression (P <
      0.01) but that RFS rates of patients with GSTP1 positive tumors were not
      significantly different from those with GSTP1 negative tumors. GSTP1 CpG islands
      hypermethylation, but not GSTP1 protein expression, is associated with a poor
      prognosis of breast cancers, suggesting that GSTP1 CpG islands hypermethylation
      has a potential to serve as a clinically useful prognostic factor.

PMID- 16791479
TI  - Estrogen receptor expression in benign breast ductal cells obtained from random
      periareolar fine needle aspiration correlates with menopausal status and
      cytomorphology index score.
AB  - INTRODUCTION: Estrogen receptor (ER) expression in breast epithelial cells has
      potential as a risk marker for development of breast cancer and as a response
      marker for preventive interventions. AIM: The purpose of this study was to
      determine if ER expression in benign cytologic specimens acquired by random
      periareolar fine needle aspiration (RPFNA) increases with morphologic abnormality
      as has been reported for histologic preparations. METHODS: ER expression was
      assessed in 122 women at high risk for development of breast cancer who had RPFNA
      hyperplasia +/- atypia and were being screened for entry into one of two
      chemoprevention trials. ER was assessed using antigen retrieval at 90 degrees C
      for 2 min and the DAKO ER monoclonal antibody (Clone number 1D5). The proportion
      of cells with definitive staining at each intensity level (0-4) was recorded as a
      percentage of the total cells counted, to give a weighted intensity score (IS).
      RESULTS: Of 122 women, 65% exhibited hyperplasia and 35% exhibited hyperplasia
      with atypia in their RPFNA specimens. A majority (66%) of subjects had at least
      10% of ductal cells exhibiting nuclear staining for ER. Median percent of cells
      with > or =1+ staining was 20% and the median ER IS was 0.23. There was a strong
      correlation between ER IS and percentage of ER positive cells (R(2) = 0.88). By
      univariate analysis ER IS was statistically significantly higher in women older
      than median age of 48 years (P = 0.025), in postmenopausal women on HRT (P <
      0.017), and in women with a Masood cytomorphology index score of > or =14 (P =
      0.005). On multivariable analysis, ER IS was significantly associated with
      postmenopausal status (P = 0.038) and cytomorphology as measured by Masood score
      (P = 0.043). CONCLUSION: ER can be readily measured in cytologic specimens
      obtained by RPFNA with the use of antigen retrieval method. Further, ER
      expression in cytologic specimens is influenced by postmenopausal status and
      morphologic abnormality.

PMID- 16791480
TI  - Secreted frizzled related protein 2 (sFRP2) decreases susceptibility to UV
      induced apoptosis in primary culture of canine mammary gland tumors by NF-kappaB
      activation or JNK suppression.
AB  - Tumor formation can result from a decrease in cell death, as well as an increase
      in cell proliferation. In spite of the high incidence of mammary gland tumors
      (MGTs) in female dogs, the understanding of its etiology is still poor.
      Consistent with several proto-oncogenes (such as Wnt) for the mammary gland,
      sFRP2 is expressed in canine MGTs which is normally silent in the mammary gland.
      To elucidate the roles of SFRP2 in the tumorigenesis of MGTs, apoptosis
      regulation mediated by sFRP2 was investigated by overexpression of sFRP2 in MGT
      cells. DNA fragmentation and TUNEL assays showed a decreased susceptibility of
      the cells to UV-induced apoptosis in the context of sFRP2 overexpression. To
      analyze the pathways through which sFRP2 transduces anti-apoptosis signals,
      multiple-color immunofluorescence staining, immunoprecipitation, and
      immunoblotting were carried out. sFRP2 was found co-localized in the
      extracellular matrix of MGTs and the tyrosine phosphorylation of FAK was
      enhanced. Moreover, JNK was suppressed and NF-kB was activated in the cells
      expressing sFRP2 after UV-induced apoptosis analyzed by immunoblotting and
      electrophoretic mobility shift assay (EMSA). Taken together, these results
      suggest that sFRP2 exerts its anti-apoptotic function in mammary cancer cells
      through NF-kappaB activation or JNK suppression.

PMID- 16791481
TI  - Factors affecting sensitivity and specificity of screening mammography and MRI in
      women with an inherited risk for breast cancer.
AB  - BACKGROUND: The MRISC study is a screening study, in which women with an
      increased risk of hereditary breast cancer are screened by a yearly mammography
      and MRI, and half-yearly clinical breast examination. The sensitivity found in
      this study was 40% for mammography and 71% for MRI and the specificity was 95 and
      90%, respectively. In the current subsequent study we investigated whether these
      results are influenced by age, a BRCA1/2 mutation, menopausal status and breast
      density. PATIENTS AND METHODS: From November 1999 to October 2003, 1909 eligible
      women were screened and 50 breast cancers were detected. For the current
      analysis, data of 4134 screening rounds and 45 detected breast cancers were used.
      For both imaging modalities, screening parameters, receiver operating
      characteristic (ROC) curves and uni- and multivariate odds ratios (ORs) were
      calculated. All analyses were separately performed for age at entry (< 40, 40-49,
      > or =50), mutation status, menopausal status and breast density. RESULTS:
      Sensitivity of MRI was decreased in women with high breast density (adjusted OR
      0.08). False-positive rates of both mammography (OR(adj) 1.67) and MRI (OR(adj)
      1.21) were increased by high breast density, that of MRI by pre-menopausal status
      (OR(adj) 1.70), young age (OR(adj) 1.58 for women 40-49 years versus women > or
      =50 years) and decreased in BRCA1/2 mutation carriers (OR(adj) 0.74). In all
      investigated subgroups the discriminating capacity (measured by the area under
      the ROC-curve) was higher for MRI than for mammography, with the largest
      differences for BRCA1/2 mutation carriers (0.237), for women between 40 and 49
      years (0.227) and for women with a low breast density (0.237). CONCLUSIONS: This
      report supports the earlier recommendation that MRI should be a standard
      screening method for breast cancer in BRCA1/2 mutation carriers.

PMID- 16791482
TI  - Genetic determinants of bone mass do not relate with breast cancer risk in US
      white and African-American women.
AB  - INTRODUCTION: The association between high bone mass and increased breast cancer
      risk has been established. Identification of polymorphisms and the resultant
      variant receptors suggests the possibility of differential effects on hormone
      responsive genes when complexed with the hormones. Both estrogen receptor-alpha
      (ER) and vitamin D receptor (VDR) polymorphisms have been associated with bone
      density. Thus, we examined these polymorphisms for association with increased
      breast cancer risk among US African-American and white women. METHODS: A case
      control study was conducted to measure ER and VDR polymorphisms and radial bone
      mineral density (BMD) in African-American and white women, and to examine the
      association between polymorphisms, bone density and breast cancer risk. Genotypes
      and bone density were obtained from 412 women (220 cases and 192 controls, with
      equal distribution between the two ethnic groups). RESULTS: We found no evidence
      for an association between either the ER or VDR genotypes and breast cancer risk.
      Also, there was no difference in the risk of breast cancer by genotypes after
      adjusting for ethnicity. The addition of age, sex and ethnicity-specific BMD (Z
      scores) did not significantly change the odds ratio for breast cancer.
      CONCLUSIONS: Our data suggest that the polymorphisms investigated had no effect
      on risk of breast cancer in this population. Thus, we found no evidence to
      support our hypothesis that breast cancer cases and controls would have a
      different distribution of ER and VDR genotypes. Furthermore, the polymorphisms
      were not associated with differences in bone mass and its relationship with
      breast cancer risk.

PMID- 16791483
TI  - Serum selenium measurements in women with early-stage breast cancer with and
      without chemotherapy-induced ovarian failure.
AB  - Blood selenium has been shown to decline as breast cancer progresses and
      fluctuate with estrogen. The objective of this study was to determine the effect
      of estrogen depletion resulting from chemotherapy-induced ovarian failure on
      serum selenium and selenoproteins in stage I/II premenopausal breast cancer
      patients. Serum selenium, glutathione peroxidase (GPx) activity, and
      selenoprotein P (SelP) were measured and a dietary questionnaire was completed at
      baseline (before chemotherapy) and 6, 12, and 24 months after start of
      chemotherapy. Twelve months after the start of adjuvant chemotherapy 33 (75%)
      patients developed ovarian failure (OF) and 11 (25%) retained menstrual function
      (non-OF). Dietary selenium intake was 30-58% above the Recommended Dietary
      Allowance for both groups. By six months the mean estradiol (pg/ml) was lower in
      the OF group than in the non-OF group (32+/-5 versus 140+/-62 pg/ml, p=0.01) and
      this difference was maintained at 12 and 24 months. However, there was no
      differences in serum selenium, GPx activity, or SelP in the OF and non-OF groups
      at 6, 12, and 24 months. Selenium status in premenopausal breast cancer patients,
      as measured by serum selenium, GPx and SelP, was within the normal range before
      and following adjuvant chemotherapy, and was not affected by chemotherapy-induced
      ovarian failure.

PMID- 16791484
TI  - A cohort study of antihypertensive medication use and breast cancer among Danish
      women.
AB  - BACKGROUND: It has been suggested that specific antihypertensive medications
      (AHT) may either increase or decrease breast cancer risk. METHODS: We studied
      breast cancer incidence among 49,950 women in North Jutland, Denmark in order to
      determine if breast cancer risk is associated with specific classes of AHT use.
      Poisson regression analyses were used to calculate rate ratios for ever or
      exclusive use of each class of AHT, number of prescriptions for AHT, and years of
      follow-up. RESULTS: There was no statistically significant association between
      ever use of any AHT overall (RR = 0.95; 95% CI = 0.81-1.10) or any specific class
      of AHT (diuretics, beta blockers, calcium channel blockers (CCBs), angiotensin
      converting enzyme (ACE) inhibitors, and angiotensin II antagonists) and breast
      cancer. CONCLUSIONS: This study should offer further reassurance to women
      currently using AHT that their medication use is unlikely related to breast
      cancer risk.

PMID- 16791485
TI  - Human breast duct anatomy, the 'sick lobe' hypothesis and intraductal approaches
      to breast cancer.
AB  - INTRODUCTION: Information about central and peripheral duct anatomy is a
      requirement for developing intraductal approaches to human breast cancer, but
      remains sparse. This study looks at the acquisition and digital modelling of data
      describing breast duct branching from thick ('subgross') sections using data
      structures from the neurosciences, and at high-throughput imaging of duct anatomy
      in the nipple. METHODS: The branching of a large breast duct system was modelled
      using data extracted from cleared and stained 2 mm 'subgross' sections of an
      autopsy breast using a public-domain neuron modelling program (CVAPP), and
      episcopic fluorescence image capture (EFIC) was used to collect a stack of 1100
      autofluorescence images of ducts in a mastectomy nipple. RESULTS: The duct
      skeleton was captured in 440 line segments with some pruning of terminal ducts.
      Extracting this data manually in a usable form was, however, laborious and error
      prone, emphasising the need for improved morphological informatics. EFIC captured
      anatomical detail and subsequent 3D reconstruction was consistent with the
      distinction between 'type A' and 'type B' nipple ducts proposed by Going and
      Moffat (J Pathol 203: 538-544, 2004). CONCLUSIONS: Whole-lobe duct modelling and
      EFIC reveal central and peripheral duct anatomy in human breast. Such knowledge
      is required for understanding normal breast development, the growth of cancer
      precursors, and for developing the intraductal approach to breast cancer.

PMID- 16791486
TI  - Genome-wide analysis for loss of heterozygosity in primary and recurrent
      phyllodes tumor and fibroadenoma of breast using single nucleotide polymorphism
      arrays.
AB  - Phyllodes tumors of the breast are biphasic stromal and epithelial tumors
      histologically similar to benign fibroadenomas, but with a neoplastic stromal
      component. In contrast to fibroadenoma, phyllodes tumors can recur and be locally
      aggressive or be malignant. This study uses SNP array analysis to present a
      genome-wide map of loss of heterozygosity (LOH) in a cohort of phyllodes tumors
      and fibroadenomas. LOH is frequent and sometimes extensive in phyllodes tumors,
      but is rarely seen in fibroadenomas. There is heterogeneity between phyllodes
      tumors of different patients and no one LOH marker identifies a majority of these
      lesions. However, a subset of LOH loci occur in multiple cases of phyllodes
      tumors and are not found in fibroadenomas. Primary phyllodes tumors and paired
      recurrences from the same patient share common regions of LOH. In contrast,
      metachronous fibroadenomas from the same patient have different LOH patterns with
      no indication of a shared origin. Specific LOH loci may be associated with
      pathologic progression in recurrent phyllodes tumors. In a single case of
      phyllodes tumor containing a malignant epithelial component the malignant
      epithelium and stroma partially share an LOH genotype, suggesting a common
      precursor cell for the biphasic malignant components.

PMID- 16791487
TI  - The "Sentinel Chain": a new concept for prediction of axillary node status in
      breast cancer patients.
AB  - BACKGROUND AND OBJECTIVES: More than half the breast cancer patients with
      positive sentinel lymph nodes (SLN) do not harbor additional metastases in non
      sentinel nodes (NSN). The aim of this study was to identify a subgroup of
      patients with positive SLNs and negative NSNs, on the basis of tumor involvement
      patterns in multiple radioactive nodes. METHODS: Between 2000 and 2004, 290
      patients with primary invasive breast cancer and clinically negative axillary
      nodes had a SLN biopsy in our breast unit. Radiotracer was identified
      intraoperatively in the axilla. All radioactive nodes were removed and
      radioactivity was measured in each node extracorporeally. Nodes were ranked
      according to radioactivity, constituting a "Sentinel Chain", and the
      histopathological status of each node was reported. The different metastatic
      involvement patterns of the Sentinel Chain were correlated with the metastatic
      status of the NSNs after axillary dissection. Information was charted in a
      prospective database. RESULTS: Of 290 patients, 216 (74.5%) had multiple
      radioactive nodes. Ninety patients (31%) had SLN metastases. Fifty patients had
      multiple ranked radioactive nodes and positive SLNs. Twenty-five of these
      patients had a sequential involvement pattern, with tumor-bearing high
      radioactivity nodes, and uninvolved low-radioactivity nodes. In the 23 of these
      25 patients who had axillary dissection, NSN involvement was detected in only one
      patient (4.3%), whereas in 24 patients with other involvement patterns of the
      Sentinel Chain, NSN involvement reached 54.2% (p<0.001). CONCLUSION: Tumor-free
      status of NSN may be predicted using the Sentinel Chain concept in some breast
      cancer patients with positive SLNs.

PMID- 16791488
TI  - Expression and clinical signification of cytosolic hyaluronan levels in invasive
      breast cancer.
AB  - BACKGROUND: Hyaluronic acid (HA), a high-molecular weight glycosaminoglycan, has
      been considered to be involved in the growth and progression of malignant tumors
      in several experimental studies. The objective of this work was to evaluate the
      cytosolic HA content in breast cancer, its possible relationship with
      clinicopathological tumor parameters and steroid receptor status, as well as its
      potential prognostic significance. METHODS: Cytosolic HA levels were examined by
      means of immunoradiometric techniques in 850 patients with invasive breast
      cancer. The mean follow-up period for these patients was 55.1 months. RESULTS:
      Cytosolic HA levels ranged widely in tumors (4-59767 ng/mg protein; median:
      4960). Statistical analysis showed that HA levels were significantly higher in
      younger patients (p=0.0001), as well as in premenopausal than in postmenopausal
      patients (p=0.001). HA levels were also significantly higher in ductal or lobular
      histological type than in other histological types (coloid, medullar or papillar
      types) (p=0.0001). Likewise, HA correlated significantly and positively with
      tumoral levels of PgR (r sub S: 0.11; p=0.001) in the all group of patients. In
      the subgroup of patients with ductal invasive type, HA levels were also
      significantly higher in well differentiated tumors and in diploid tumors. In
      addition, in this latter group of patients, HA levels in tumors correlated also
      positively and significantly with the either estrogen-inducible proteins: PgR (r
      sub S: 0.11; p=0.001), pS2 (r sub S: 0.117; p=0.008) and tPA (r sub S: 0.314;
      p=0.0001). On the other hand, significant association between HA intratumoral
      levels and relapse-free survival and overall survival in the overall group of
      patients was not found. However, high HA intratumoral levels were significantly
      associated with longer relapse-free survival in the subgroup of patients with
      ductal histological type tumors (p=0.01), as well as in those patients without
      any type of systemic adjuvant treatment (p=0.01). CONCLUSIONS: Our results
      suggest that high intratumoral levels of HA may be associated with tumors of
      favorable evolution in certain subgroups of patients with breast cancer. Thus, HA
      may provide additional prognostic information to that given by other biochemical
      markers currently used in breast cancer.

PMID- 16791489
TI  - Styrene and breast cancer incidence in Texas: a comment on an ecological
      association.

PMID- 16791490
TI  - Comment to Anderson WF, Jatoi I, Devesa SS: distinct breast cancer incidence and
      prognostic patterns in the NCI'S SEER program: suggesting a possible link between
      etiology and outcome. Breast Cancer Res Treat 90:127-137, 2005.

PMID- 16791491
TI  - Fluid-wall modelling of mass transfer in an axisymmetric stenosis: effects of
      shear-dependent transport properties.
AB  - Mechanical forces, such as low wall shear stress (WSS), are implicated in
      endothelial dysfunction and atherogenesis. The accumulation of low density
      lipoprotein (LDL) and hypoxia are also considered as main contributing factors in
      the development of atherosclerosis. The objective of this study was to
      investigate the influences of WSS on arterial mass transport by modelling the
      flow of blood and solute transport in the lumen and arterial wall. The Navier
      Stokes equations and Darcy's Law were used to describe the fluid dynamics of the
      blood in the lumen and wall respectively. Convection-diffusion-reaction equations
      were used to model LDL and oxygen transport. The coupling of fluid dynamics and
      solute dynamics at the endothelium was achieved by the Kedem-Katchalsky
      equations. A shear-dependent hydraulic conductivity relation extracted from
      experimental data in the literature was employed for the transport of LDL and a
      shear-dependent permeability was used for oxygen. The integrated fluid-wall model
      was implemented in Comsol Multiphysics 3.2 and applied to an axisymmetric
      stenosis. The results showed elevated LDL concentration and reduced oxygen
      concentration in the subendothelial layer of the arterial wall in areas where WSS
      is low, suggesting that low WSS might be responsible for lipid accumulation and
      hypoxia in the arterial wall.

PMID- 16791492
TI  - Nonlinear dependence of hydraulic conductivity on tissue deformation during
      intratumoral infusion.
AB  - Efficiency of intratumoral infusion for drug and gene delivery depends on
      intrinsic tissue structures as well as infusion-induced changes in these
      structures. To this end, we investigated effects of infusion pressure (P(inf))
      and infusion-induced tissue deformation on infusion rate (Q) in three mouse tumor
      models (B16.F10, 4T1, and U87) and developed a poroelastic model for interpreting
      data and understanding mechanisms of fluid transport in tumors. The collagen
      concentrations in these tumors were 2.9+/-1.2, 12.2+/-0.9, and 18.1+/-3.5
      microg/mg wet wt. of tissues, respectively. During the infusion, there existed a
      threshold infusion pressure (P(t)), below which fluid flow could not be
      initiated. The values of P(t) for these tumors were 7.36, 36.8, and 29.4 mmHg,
      respectively. Q was a bell-shaped function of P(inf) in 4T1 tumors but increased
      monotonically with increasing P(inf) in other tumors. These observations were
      consistent with results from numerical simulations based on the poroelastic
      model, suggesting that both the existence of P(t) and the nonlinear relationships
      between Q and P(inf) could be explained by infusion-induced tissue deformation
      that anisotropically affected the hydraulic conductivity of tissues. These
      results may be useful for further investigations of intratumoral infusion of
      drugs and genes.

PMID- 16791494
TI  - The Calibration Kit Spectral Fluorescence Standards--a simple and certified tool
      for the standardization of the spectral characteristics of fluorescence
      instruments.
AB  - With the Calibration Kit Spectral Fluorescence Standards BAM-F001-BAM-F005, we
      developed a simple tool for the characterization of the relative spectral
      responsivity and the long-term stability of the emission channel of fluorescence
      instruments under routine measurement conditions thereby providing the basis for
      an improved comparability of fluorescence measurements and eventually
      standardization. This first set of traceable fluorescence standards, which links
      fluorescence measurements to the spectral radiance scale in the spectral range of
      300-770 nm and has been optimized for spectrofluorometers, can be employed for
      different measurement geometries and can be adapted to different fluorescence
      techniques with proper consideration of the underlying measurement principles.

PMID- 16791493
TI  - Towards control of aggregational behaviour of alpha-lactalbumin at acidic pH.
AB  - alpha-Lactalbumin (alpha-La) undergoes considerable structural changes upon loss
      of bound Ca2+ at acidic pH, leaving alpha-La in a molten globule structure. Using
      fluorescence the present work provides more insight into the structural
      transition of alpha-La at acidic pH leading to protein aggregation, most likely
      caused by a combination of hydrophobic and electrostatic interactions. The rate
      of aggregation is determined by the protein concentration and temperature
      applied. Availability of Ca2+ stabilises the protein, and thus prevent
      aggregation at pH values as low as pH 2.9. In contrast, presence of Cu2+ induces
      a destabilisation of the protein, which can be explained by a binding to the Zn2+
      binding site in alpha-La, possibly resulting in structural alterations of the
      protein. In general, presence of anions destabilize alpha-La at pH values below
      pI, with SO4(2-) exhibiting the strongest effect on the protein stability, thus
      correlating well with the Hofmeister series. At more acidic pH values far from
      pI, alpha-La becomes more stable towards ion induced aggregation, since higher
      ion activity is required to efficiently screen the charges on the protein
      surface. The results presented in this paper provide detailed knowledge on the
      external parameters leading to aggregation of alpha-La at acidic pH, thus
      permitting rational design of the aggregation process.

PMID- 16791495
TI  - Studies on the interaction of tricyclazole with beta-cyclodextrin and human serum
      albumin by spectroscopy.
AB  - The interaction of tricyclazole (TCZ) with beta-cyclodextrin (beta-CD) and human
      serum albumin (HSA) were studied by fluorescence spectrum, UV-visible spectrum
      and second-order scattering technology. It was shown that TCZ has quite a strong
      ability to quench the fluorescence launching from HSA by reacting with it and
      forming a certain kind of new compound. The quenching and the energy transfer
      mechanisms were discussed, respectively. The binding constants and thermodynamic
      parameters at four different temperatures, the binding locality, and the binding
      power were obtained. The conformation of HSA was discussed by synchronous and
      three-dimensional fluorescence techniques. The inclusion reaction between beta-CD
      and TCZ was explored by scattering method, the inclusion constants and the
      thermodynamic parameters at 297 K and 311 K were figured out, respectively. The
      mechanism of inclusion reaction was speculated and linkage among the toxicity of
      TCZ, the exterior environment and its concentration was attempted to explain on
      molecule level.

PMID- 16791497
TI  - Photoluminescence and optical absorption of Cs2NaScF6:Cr3+.
AB  - The main objective of this paper is the characterization of the spectroscopic
      properties of new materials that are prospective laser media. This approach
      allows for the comparison of the properties of the Cr3+ in different
      environments. Here, we have studied the photoluminescence and optical absorption
      of Cs2NaScF6:Cr3+ single crystals. On the basis of near-infrared luminescence
      measurements at 2, 77, and 300 K the observed lines originated from the Cr3+
      centres were associated with the 4T2(4F) --> 4A2(4F) transition and the lifetimes
      were obtained. In spite of the quenching observed as a function of temperature at
      least 10% of the 2 K emission intensity for Cs2NaScF6 doped with 1% of Cr3+
      remains at room temperature. Besides, the 2 K emission broad band could be well
      described in terms of normal modes of the octahedral complex [CrF6]3-, and the
      Racah and crystal-field parameters calculated.

PMID- 16791496
TI  - Metal-enhanced chemiluminescence.
AB  - In this short paper we report the interactions of silver island films with
      chemiluminescing species. Our findings show that silver island films can increase
      the detectability of chemiluminescent reactions/species, with an approximately 5
      fold increase in signal intensity. This finding not only suggests the use of
      silver nanostructures to amplify chemiluminscent signatures in assay platforms,
      and therefore increase the detectability of analytes or biospecies, but more
      importantly, suggests that surface plasmons can be directly excited by chemically
      induced electronically excited molecules. This finding is of significance towards
      our understanding of fluorophore-metal interactions, a relatively new near-field
      fluorescence concept, recently named metal-enhanced fluorescence and also
      radiative decay engineering.

PMID- 16791498
TI  - CT-operated bifunctional fluorescent probe based on a pretwisted donor-donor
      biphenyl.
AB  - Taking into account the structural requirements for TICT-type sensor molecules, a
      general synthetic route to derive pH and cation-responsive pretwisted donor (D)
      donor (D) biphenyls (b) equipped with donor receptors is developed and a first
      model compound containing a mono aza-15-crown-5 and a DMA receptor is
      synthesized, see Scheme 1. The spectroscopic properties of this new bifunctional
      D-D biphenyl are studied in the non-polar and polar solvents cyclohexane,
      acetonitrile, and methanol. Protonation as well as complexation studies are
      performed with the representative metal ions Na(I), K(I), Ca(II), Ag(I), Zn(II),
      Cd(II), Hg(II), and Pb(II) to reveal the potential of this molecule for
      communication of whether none, only one, or both binding sites are engaged in
      analyte coordination by spectroscopically distinguishable outputs. The results
      are compared to those obtained with closely related donor (D)-acceptor (A)
      substituted biphenyl-type sensor molecules and are discussed within the framework
      of neutral and ionic D-A biphenyls.

PMID- 16791499
TI  - An equilibrium and a kinetic stopped-flow fluorescence study of the binding of
      various metal ions to goat alpha-lactalbumin.
AB  - Various metal ions bind to the protein alpha-lactalbumin prepared from goat milk.
      The stability of the protein after metal binding is compared with that of the apo
      protein by monitoring the fluorescence of the tryptophan residues under
      equilibrium conditions. The kinetics of the metal binding is studied by stopped
      flow fluorescence spectroscopy. By means of the Arrhenius plots, the activation
      energy with regard to the binding of the different ions is determined.

PMID- 16791500
TI  - Excimer fluorescence as a tool for monitoring protein domain dynamics applied to
      actin conformation changes based on circulary polarized fluorescence
      spectroscopy.
AB  - Fluorescence-detected circular dichroism (FDCD) was introduced into the study of
      protein conformation changes. Actin was used as a model protein which undergoes
      dynamic conformation changes as it polymerizes. Actin labeled with N-(1
      pyrene)iodoacetamide (PIA) showed monomer fluorescence peak at 386 and 410 nm,
      and excimer fluorescence peak at around 480 nm. Excimer was formed by PIA-dimers
      labeled to different sites of amino acid residues. New information concerned with
      actin structural changes were monitored by fluorescence emission spectra excited
      with left- and right-circulary polarized light at 355 nm. FDCD intensities were
      shown as the difference in the fluorescence emission DeltaF, where DeltaF=(F (L)
      F (R))/(F (L)+F (R)) denoting F (L) and F (R) as emissions obtained by excitation
      with left- and right-circulary polarized light. When solvent conditions of PIA
      actin were changed by addition of NaCl, TFE, or ATP, DeltaF showed sensitive
      responses to these compounds. From the analysis of DeltaF (M) and DeltaF (E)
      which represent the peaks of DeltaF at the monomer- and excimer-emission band,
      the information concerned with the actin intrastructural changes were obtained.
      This method based on monitoring the excimer fluorescence with FDCD could be used
      for other proteins to extract finer structural changes that cannot be detected by
      the normal fluorescence spectroscopy.

PMID- 16791501
TI  - Spectral and luminescent properties and electroluminescence of polyvinylcarbazole
      with 1,8-naphthalimide in the side chain.
AB  - A novel copolymer with moieties capable of charge transport and light emission on
      the basis of polyvinylcarbazole and 1,8-naphthalimide is synthesized. A bright
      and stable electroluminescence from single layered structure is observed. White
      light emission can be easily realized by tuning the content of naphthalimide
      moieties or a number of naphthalimide derivatives. Such approach can be
      considered as a common way to create single layered light-emitting devices with a
      stable white emission.

PMID- 16791503
TI  - Characterization of TiO2 nanoparticles in Langmuir-Blodgett films.
AB  - In this work we have synthesized TiO2 nanoparticles, using either a sol-gel base
      catalysed process in the interior of CTAB reversed micelles (TiO2 CTAB sol), or
      the neutralization of a TiO2/H2SO4 solution in the interior of AOT reversed
      micelles. From the absorption and emission data of the TiO2 nanoparticles it is
      possible to conclude that in the sol-gel route there remains alkoxide groups in
      the structure, originating transitions lower than the energy gap of TiO2
      semiconductor. These transitions disappear in the neutralization procedure, where
      the alkoxide groups are absent in the structure. We have assigned the observed
      indirect and direct optical transitions according to the anatase band structure.
      TiO2 Langmuir-Blodgett (LB) films were prepared either by direct deposition of
      titanium isopropoxide or by deposition of the TiO2 CTAB sol. These films showed
      photoluminescence, which was attributed to band-gap emission and to surface
      recombination of defect states.

PMID- 16791502
TI  - Two-photon excited fluorescence energy transfer: a study based on oligonucleotide
      rulers.
AB  - The use of two-photon excitation of fluorescence for detection of fluorescence
      resonance energy transfer (FRET) was studied for a selected fluorescent donor
      acceptor pair. A method based on labeled DNA was developed for controlling the
      distance between the donor and the acceptor molecules. The method consists of
      hybridization of fluorescent oligonucleotides to a complementary single-stranded
      target DNA. As the efficiency of FRET is strongly distance dependent, energy
      transfer does not occur unless the fluorescent oligonucleotides and the target
      DNA are hybridized. A high degree of DNA hybridization and an excellent FRET
      efficiency were verified with one-photon excited fluorescence studies. Excitation
      spectra of fluorophores are usually wider in case of two-photon excitation than
      in the case of one-photon excitation. This makes the selective excitation of
      donor difficult and might cause errors in detection of FRET with two-photon
      excited fluorescence. Different techniques to analyze the FRET efficiency from
      two-photon excited fluorescence data are discussed. The quenching of the donor
      fluorescence intensity turned to be the most consistent way to detect the FRET
      efficiency. The two-photon excited FRET is shown to give a good response to the
      distance between the donor and the acceptor molecules.

PMID- 16791504
TI  - Effect of lumophore and plasticiser concentration on the heterogeneity of oxygen
      quenching in thin film oxygen sensors.
AB  - Kinetic heterogeneity of the luminescence decay and oxygen quenching of Pt and Pd
      octaethylporphyrin/ethyl cellulose (OEP/EC) thin film oxygen sensors has been
      investigated with respect to (a) concentration of lumophore and (b) addition of
      plasticiser. The source of kinetic heterogeneity shown by PtOEP films under N2 is
      a monomer-dimer equilibrium in which the dimer luminescence decays with k =
      0.0527 x 10(6) s(-1) and the monomer luminescence with k = 0.0101 x 10(6) s(-1)
      and KD = 790 (+/-20) mol dm(-3). For PdOEP/EC films there is no detectable
      aggregation and luminescence decays under N2 show good fits to single exponential
      curve fits at all concentrations studied. The addition of either tripbutyl
      phosphate or dimethylphthalate as plasticiser does not decrease kinetic
      heterogeneity for oxygen quenching of luminescence in the films.

PMID- 16791505
TI  - Nanocrystalline RE2O3:Tm3+ (RE: Gd3+, Y3+) blue phosphors synthesized via the
      combustion method.
AB  - This work reports on the preparation of a luminescent blue-emitting rare earth
      (RE) Tm-doped oxide phosphor. Nanocrystalline RE2O3:Tm3+ particles were prepared
      via the combustion method using citric acid, glycine, or urea as fuels. Samples
      were doped with different percentages of the activator Tm3+. The post-annealing
      treatment was performed in air for all the samples, at temperatures ranging from
      800 to 1100 degrees C, for 4 h. The samples were characterized by X-ray
      diffraction (XRD), photoluminescence spectroscopy (PL) and scanning electron and
      transmission microscopies (SEM and TEM) in order to determine the best synthetic
      procedure. The post-annealed powders showed blue emission with maximum at 452 nm
      characteristics for Tm3+ transition 1D2 --> 3H4 (under UV excitation at 360 nm).
      Samples, presented a tri-dimensional porous structure (50-200 nm) formed of
      spheroid particles with a diameter between 20 and 60 nm. The best luminescent
      material was obtained when urea was used to prepare nanoparticles of Gd2O3 doped
      with 0.5% Tm3+, and 1100 degrees C was used as the post-annealing temperature.

PMID- 16791506
TI  - Study of the interaction between Apis mellifera venom and micro-heterogeneous
      systems.
AB  - The bee venom, used in treatment of inflammatory and articular diseases, is a
      complex mixture of peptides and enzymes and the presence of tryptophan allows the
      investigation by fluorescence techniques. Steady state and time-resolved
      fluorescence spectroscopy were used to study the interaction between bee venom
      extracted from Apis mellifera and three micro heterogeneous systems: sodium
      dodecylsulphate (SDS) micelles, sodium dodecylsulphate-poly(ethylene oxide) (SDS
      PEO) aggregates, and the polymeric micelles LUTROL F127, formed by poly(ethylene
      oxide)-poly(propylene oxide)- poly(ethylene oxide). Fluorescence parameters in
      buffer solution were typical of peptides containing tryptophan exposed to the
      aqueous medium, and they gradually changed upon the addition of surfactant and
      polymeric micelles, demonstrating the interaction of the peptides with the micro
      heterogeneous systems. Quenching experiments were carried out using the N
      alkylpyridinium ions (ethyl, hexyl, and dodecyl) as quenchers. In buffer solution
      the quenching has low efficiency and is independent of the alkyl chain length of
      the quencher. In the presence of the micro heterogeneous systems the extent of
      static and dynamic quenching enhanced, showing that both fluorophore and
      quenchers reside in the microvolume of the aggregates. The more hydrophobic
      quencher (dodecyl pyridinium ion) provides higher values for K (SV) and dynamic
      quenching constants, and SDS-PEO aggregates are most efficient to promote
      interaction between peptides and alkyl pyridinium ions. The results proved that
      bee venom interacts with drug delivery micelles of the copolymer LUTROL F127.

PMID- 16791507
TI  - Laurdan in fluid bilayers: position and structural sensitivity.
AB  - Laurdan (2-dimethylamino-6-lauroylnaphthalene) is a hydrophobic fluorescent probe
      widely used in lipid systems. This probe was shown to be highly sensitive to
      lipid phases, and this sensitivity related to the probe microenvironment polarity
      and viscosity. In the present study, Laurdan was incorporated in 1,2-dipalmitoyl
      sn-glycero-3-[phospho-rac-(1-glycerol)] (DPPG), which has a phase transition
      around 41 degrees C, and DLPC (1,2-dilauroyl-sn-glycero-3-phosphocholine), which
      is in the fluid phase at all temperatures studied. The temperature dependence of
      Laurdan fluorescent emission was analyzed via the decomposition into two gaussian
      bands, a short- and a long-wavelength band, corresponding to a non-relaxed and a
      water-relaxed excited state, respectively. As expected, Laurdan fluorescence is
      highly sensitive to DPPG gel-fluid transition. However, it is shown that Laurdan
      fluorescence, in DLPC, is also dependent on the temperature, though the bilayer
      phase does not change. This is in contrast to the rather similar fluorescent
      emission obtained for the analogous hydrophilic probe, Prodan (2-dimethylamino-6
      propionylnaphthalene), when free in aqueous solution, over the same range of
      temperature. Therefore, Laurdan fluorescence seems to be highly dependent on the
      lipid bilayer packing, even for fluid membranes. This is supported by Laurdan
      fluorescence anisotropy and spin labels incorporated at different positions in
      the fluid lipid bilayer of DLPC. The latter were used both as structural probes
      for bilayer packing, and as Laurdan fluorescence quenchers. The results confirm
      the high sensitivity of Laurdan fluorescence emission to membrane packing, and
      indicate a rather shallow position for Laurdan in the membrane.

PMID- 16791508
TI  - Fluorescence spectroscopic studies on plasma-chemically modified polymer surfaces
      with fluorophore-labeled functionalities.
AB  - Molecular engineering of polymer surfaces that includes the attachment of
      functional molecules to existing or previously generated reactive chemical groups
      like e.g., -OH, -NH2, or -CHO requires simple strategies and tools for the
      controlled generation of surface functionalities and their derivatization as well
      as for their identification and eventually quantification. Here, we
      systematically investigate the plasma-chemical surface modification of
      polypropylene films in combination with dansyl labeling chemistry and
      conventional, yet costly, XPS and highly sensitive fluorescence spectroscopy for
      the detection of surface groups. Based on these results, the potential of and
      requirements on the fluorometric characterization and quantification of surfaces
      functionalities are discussed.

PMID- 16791509
TI  - Fluorescence studies of host-guest interaction of a dansyl amide labelled
      calix[6]arene.
AB  - The fluorescence behavior of a calix[6]arene with a dansyl group as fluorescence
      marker (C6-DA) was investigated with respect to the inclusion properties of
      alkaloids as atropine and cocaine. A strong hypsochromic shift of the
      fluorescence band and a strong increase in fluorescence intensity is connected
      with the interaction of atropine to the lower rim of the C6-DA. The fluorescence
      increase is saturated at an atropine concentration above the 1:1 complex
      formation. Addition of cocaine to the complexed atropine-C6-DA leads to a
      decrease of the fluorescence intensity which could be explained by an exchange
      mechanism of the complexed molecules. The complexation of the atropine (the
      "belladonna effect") is interpreted by electrostatic interaction (proton transfer
      from the carboxylic group to the nitrogen) with important contribution from
      hydrogen bonding by the guest OH-group.

PMID- 16791510
TI  - Photophysical properties of new terbium (III) organophosphonates.
AB  - This paper reports on the synthesis, characterization and photophysical
      properties of the Tb3+ organophosphonates, TbH(O3PR)2, methylphosphonate (R =
      CH3), ethylphosphonate (R = C2H5), propylphosphonate (R = C3H7), and
      phenylphosphonate (R = C6H5). The layered Tb3+ organophosphonates were
      characterized by X-ray diffraction, IR spectroscopy, TG and elemental analysis.
      The interlayer distances of the Tb3+ organophosphonates evaluated by the X-ray
      diffractogram were 9.50 Angstrom for TbH(O3PCH3)2, 12.18 Angstrom for
      TbH(O3PC2H5)2, 14.84 Angstrom for TbH(O3PC3H7)2 and 15.20 Angstrom for
      TbH(O3PC6H5)2. The Tb3+ luminescence data revealed highly green emissive
      materials when they were excited at 368 nm, where the characteristic 5D4 --> 7FJ
      (J=6, 5, 4 and 3) transitions of Tb3+ were observed at 488, 543, 585 and 619 nm,
      respectively. The lifetime of the Tb(3+ 5)D4 --> 7F5 transition (lambda(exc)=368
      nm and lambda(em)=543 nm) for the Tb3+ organophosphonates was evaluated from the
      decay curves, which values were of 2.88, 2.22, 2.14 and 2.59 ms, respectively for
      TbH(O3PCH3)2, TbH(O3PC2H5)2, TbH(O3PC3H7)2 and TbH(O3PC6H5)2. TG analysis
      revealed that these materials are thermally highly stable, with no water molecule
      in their composition, which makes them potential luminophores.

PMID- 16791511
TI  - Er, Yb doped yttrium based nanosized phosphors: particle size, "host lattice" and
      doping ion concentration effects on upconversion efficiency.
AB  - The upconverter phosphors studied herein have different percentages of Er3+ and
      Yb3+ as doping ions in different Y3+ matrixes (Y2O3, Y2O2S), and were prepared
      from different precursors (polymeric resin, oxalate, basic carbonate) and method
      (combustion). Upconversion emission spectra were recorded at 298 K for all the
      doped samples in the visible region, for efficiency and Green/Red emission
      relative intensity comparisons. Therefore, an investigation of the influence of
      the doping ion concentration, particle size and host lattice on the upconversion
      process is provided in view of the UPT (Upconverting phosphor technology
      application). On the basis of the results, it was possible to evaluate the best
      combination for a specific assay, considering whether it is advantageous to have
      the greatest contribution from the green or red emissions, or from both in
      comparable intensities.

PMID- 16791512
TI  - Psychometrics of the MHSIP Adult Consumer Survey.
AB  - The reliability and validity of the Mental Health Statistics Improvement Program
      (MHSIP) Adult Consumer Survey were assessed in a statewide convenience sample of
      459 persons with severe mental illness served through a public mental health
      system. Consistent with previous findings and the intent of its developers, three
      factors were identified that demonstrate good internal consistency, moderate test
      retest reliability, and good convergent validity with consumer perceptions of
      other aspects of their care. The reliability and validity of the MHSIP Adult
      Consumer Survey documented in this study underscore its scientific and practical
      utility as an abbreviated tool for assessing access, quality and appropriateness,
      and outcome in mental health service systems.

PMID- 16791513
TI  - Community-based interdisciplinary research: introduction to the special issue.
AB  - This special issue on community-based interdisciplinary research grew out of the
      work of the SCRA Interdisciplinary Task Force and an Interdisciplinary Working
      Conference held at Vanderbilt University in May, 2004. In this introduction to
      the special issue, the historical context for interdisciplinary underpinnings for
      community psychology theory, research, action and training is first depicted.
      This is followed by a brief description of the mission and work of the recent
      SCRA Interdisciplinary Task Force and the Interdisciplinary Working Conference.
      The introduction concludes with a brief summary of the papers in the two main
      sections of the special issue, Prospects and Perspectives (four scholarly papers
      and three commentaries) and Community-Based Interdisciplinary Action-Research
      (four interdisciplinary action-research projects).

PMID- 16791514
TI  - Toward a science of transdisciplinary action research.
AB  - This paper offers a conceptual framework for establishing a science of
      transdisciplinary action research. Lewin's (1951) concept of action research
      highlights the scientific and societal value of translating psychological
      research into community problem-solving strategies. Implicit in Lewin's
      formulation is the importance of achieving effective collaboration among
      behavioral researchers, community members and policy makers. The present analysis
      builds on Lewin's analysis by outlining programmatic directions for the
      scientific study of transdisciplinary research and community action. Three types
      of collaboration, and the contextual circumstances that facilitate or hinder
      them, are examined: (1) collaboration among scholars representing different
      disciplines; (2) collaboration among researchers from multiple fields and
      community practitioners representing diverse professional and lay perspectives;
      and (3) collaboration among community organizations across local, state,
      national, and international levels. In the present analysis, transdisciplinary
      action research is viewed as a topic of scientific study in its own right to
      achieve a more complete understanding of prior collaborations and to identify
      strategies for refining and sustaining future collaborations (and their intended
      outcomes) among researchers, community members and organizations.

PMID- 16791515
TI  - Realities and myths of safety issues for community researchers working in a
      marginalized African American community.
AB  - Community psychologists often conduct research in collaboration with marginalized
      communities in which safety is an issue. However, we rarely talk about what
      specific safety issues we experience and how we deal with them. Our story
      describes the realities and myths of neighborhood safety that were experienced in
      a low-income African American neighborhood of Chicago, while collaborating on a
      project designed to increase access to the Internet to obtain health information.
      We examine both the challenges experienced and our responses in the context of a
      community intervention planned, implemented, and evaluated by a partnership team
      composed of various stakeholders. Critical lessons such as the importance of
      building on community strengths and the need to be aware of our own biases are
      discussed.

PMID- 16791516
TI  - Stronger relationships, stronger communities: lessons from a regional intergroup
      grant initiative.
AB  - This paper tells the story of an intergroup grant initiative and the neighborhood
      projects it supported. It highlights the challenges of race and power, in
      conjunction with other overlapping identities and forms of discrimination. The
      demographics of the greater Goodland region have changed dramatically over the
      last few years and decades. The life for traditionally European American and
      African American communities is being altered by a steady influx of new
      immigrants from Africa, Asia, and Latin America. This paper discusses a
      philanthropic community's response to these changes and within this, two specific
      neighborhood-based responses. The lessons and insights described in this paper,
      told by the initiative's evaluator and advisory council co-chair, are drawn from
      five years' of systematic data collection and analysis, focused observations, and
      the reflections of other participants in the initiative.

PMID- 16791517
TI  - Listening to diversity stories: principles for practice in community research and
      action.
AB  - Three broad Diversity Principles for Community Research and Action are described
      and offered as community psychology's contribution to the growing literature on
      multicultural competence in psychology. The principles are applicable to multiple
      dimensions of diversity including race, ethnicity, gender, sexual orientation,
      religion, disability, and social class. The diversity principles are illustrated
      with examples from the twenty-two diversity stories in the AJCP Special Issue on
      Diversity Stories in Community Research and Action. Each of the three diversity
      principles (Community Culture, Community Context, and Self-in-Community) are
      associated with a fundamental assumption, a process emphasis (descriptive,
      analytic, and reflective), a core question to engage, an orienting stance
      (informed compassion, contextualized understanding, and empowered humility), and
      three areas of focus. Taken together, the principles suggest the value of the
      overarching stance of connected disruption. It is suggested that applying the
      principles to community work in diverse settings will facilitate the process of
      bridging differences and enhance the relevance and effectiveness of our work.

PMID- 16791518
TI  - Beyond criminalization: toward a criminologically informed framework for mental
      health policy and services research.
AB  - The problems posed by persons with mental illness involved with the criminal
      justice system are vexing ones that have received attention at the local, state
      and national levels. The conceptual model currently guiding research and social
      action around these problems is shaped by the "criminalization" perspective and
      the associated belief that reconnecting individuals with mental health services
      will by itself reduce risk for arrest. This paper argues that such efforts are
      necessary but possibly not sufficient to achieve that reduction. Arguing for the
      need to develop a services research framework that identifies a broader range of
      risk factors for arrest, we describe three potentially useful criminological
      frameworks-the "life course," "local life circumstances" and "routine activities"
      perspectives. Their utility as platforms for research in a population of persons
      with mental illness is discussed and suggestions are provided with regard to how
      services research guided by these perspectives might inform the development of
      community-based services aimed at reducing risk of arrest.

PMID- 16791519
TI  - Does learning about the effects of alcohol on the developing brain affect
      children's alcohol use?
AB  - Protecting You/Protecting Me (PY/PM) is a classroom-based, alcohol-use prevention
      and vehicle safety program for students in grades 1-5 developed by Mothers
      Against Drunk Driving (MADD). PY/PM is one of the first alcohol prevention
      programs targeting children that incorporates emerging research on the adverse
      effects of alcohol on the developing brain. In this study, we surveyed fifth
      grade students, some of whom were exposed to their fifth consecutive year of
      PY/PM implementation. Results indicate that, relative to comparison students from
      matched schools, PY/PM students increased their knowledge of the effects of
      alcohol on the developing brain, their perception of the potential harm of
      alcohol use, and their vehicle safety skills. PY/PM students also exhibited
      increased negative attitudes toward underage drinking, increased their intentions
      not to use alcohol, and reported decreased riding with an impaired driver. PY/PM
      did not have an effect on alcohol use per se of these fifth graders. Path
      modeling revealed that knowledge of the effects of alcohol on the developing
      brain had both a direct and an indirect effect on alcohol use, the latter by
      increasing perceptions of the harm of underage alcohol use which, in turn
      affected intentions to use and use itself. Teaching children about the effects of
      alcohol on the developing brain appears to be a promising strategy for underage
      alcohol use prevention.

PMID- 16791521
TI  - Adolescents' reactions to universal and indicated prevention programs for
      depression: perceived stigma and consumer satisfaction.
AB  - There is a common view that one of the major considerations in selecting between
      universal and indicated interventions is the marked stigma produced by the
      latter. However, to date there has been no empirical examination of this
      assumption. The current study examined reported stigma and program satisfaction
      following two school-based interventions aimed at preventing depression in 532
      middle adolescents. The interventions were conducted either across entire classes
      by classroom teachers (universal delivery) or in small high risk groups by mental
      health professionals (indicated delivery). The indicated delivery was associated
      with significantly greater levels of perceived stigma, but effect sizes were
      small and neither program was associated with marked stigma in absolute terms.
      Perceived stigma was more strongly associated with aspects of the individual
      including being male and showing greater externalizing symptomatology. In
      contrast, the indicated program was evaluated more positively by both
      participants and program leaders and effect sizes for these measures of
      satisfaction were moderate to large. The results point to the need for further
      empirical evaluation of both perceived stigma and program satisfaction in
      providing balanced considerations of the value of indicated and universal
      programs.

PMID- 16791520
TI  - Mediators of the stress-substance-use relationship in urban male adolescents.
AB  - Exposure to chronic or severe acute stressors throughout the lifespan has been
      linked with numerous negative behavioral, emotional, cognitive, and physical
      consequences. Adolescence is considered to be a particularly vulnerable period
      given that the brain is experiencing dramatic developmental change during this
      time. The present study examined a sample of adolescents (N=125) considered to be
      at high risk for stress exposures and drug use by virtue of their environment and
      low income levels to identify possible neurocognitive (i.e., impulsivity, delay
      of gratification, emotional perception, and risky decision-making) and social
      competency mechanisms that may mediate this relationship. Using Mplus, a
      mediational model was tested using full information maximum likelihood estimates.
      Risky decision-making and poor social competency skills were related to previous
      stressful experiences; however, only social competencies mediated the effect of
      stressors on reports of past year marijuana, alcohol, and polydrug use. As such,
      stress appears to exert its negative impact through alterations in abilities to
      generate and execute prosocial decisions and behaviors. Interventions that
      directly address the effects of stress on social competencies may be especially
      important for children who have experienced adversity including those exposed to
      parental divorce, parental psychopathology, neglect or abuse, parental death, and
      poverty.

PMID- 16791522
TI  - Bridge-it: a system for predicting implementation fidelity for school-based
      tobacco prevention programs.
AB  - Properly implemented school programs to prevent tobacco use and addiction can
      lower smoking prevalence up to 60%. However, numerous programs are not successful
      due to poor implementation. A system for estimating likelihood of future
      implementation fidelity of school-based prevention programs was tested using data
      collected at baseline and two year follow-up in 47 middle schools and high
      schools participating in the Texas Tobacco Prevention Initiative. The Bridge-It
      system includes an eight-factor, 36-item survey to analyze capacity for program
      implementation and a companion Bayesian model which provides estimations of
      likelihood of implementation fidelity several years after program initiation. The
      survey also asks about amount of implementing activity for each of the multiple
      components recommended in federal guidelines for school programs to prevent
      tobacco use. Criterion referenced cross-tabulations showed the system's forecast
      of implementation fidelity was correct in 74% of cases (p < .01). Model
      reliability was confirmed in regression analyses. Implementation fidelity at
      follow-up was predicted by the combination of the model's eight capacity factors
      at baseline. It includes program, implementation support, and non-program
      factors. Integration of the Bridge-It system, or comparable tools, into the
      dissemination and evaluation of school-based prevention programs can help to
      increase understanding of factors that influence implementation and provide
      guidance for capacity building. If administrators can identify at baseline
      schools likely to fall short of implementation goals, plans for resource
      allocation and provision of guidance, training, and technical assistance can be
      specifically tailored to identified needs.

PMID- 16791523
TI  - Universality of effects: an examination of the comparability of long-term family
      intervention effects on substance use across risk-related subgroups.
AB  - This study extends earlier investigation of family risk-related moderation of two
      brief, family-focused preventive interventions. It examines effects on the
      trajectories of substance initiation over a period of six years after a pretest
      assessment, evaluating whether effects were comparable across higher- and lower
      risk subgroups. The two interventions, designed for general-population families
      of adolescents, were the seven-session Iowa Strengthening Families Program (ISFP)
      and the five-session Preparing for the Drug Free Years program (PDFY). Thirty
      three rural public schools were randomly assigned to either the ISFP, the PDFY,
      or a minimal contact control condition. Curvilinear growth curve analyses were
      used to evaluate the universality of intervention effectiveness by testing for
      risk moderation of intervention effects on school-level substance use
      trajectories of initiation of alcohol and illicit substance use. Results were
      most consistent with the interpretation that both interventions provided
      comparable benefits for both outcome measures, regardless of family risk status.
      Findings are discussed in terms of their implications for implementing universal
      preventive interventions in general populations.

PMID- 16791524
TI  - School predictors of the intensity of implementation of school-based prevention
      programs: results from a national study.
AB  - Research has indicated that the effectiveness of school-based prevention programs
      is affected by the implementation quality of these programs. As the importance of
      implementation has become clearer, researchers have begun to examine factors that
      appear to be related to implementation quality. Data from a nationally
      representative sample of 544 schools were used to examine structural equation
      models representing hypothesized relationships among school and program factors
      and implementation intensity, controlling for exogenous community factors.
      Significant relationships were found between implementation intensity and several
      school and program factors, including local program development process,
      integration into school operations, organizational capacity, principal support,
      and standardization. Implications of these findings are discussed.

PMID- 16791525
TI  - Disclosure of HIV status and adherence to daily drug regimens among HIV-infected
      children in Uganda.
AB  - Pediatric adherence to daily drug regimens has not been widely assessed in Africa
      where majority of HIV infected children live. Using in-depth interviews of 42 HIV
      infected children taking ART and/or cotrimoxazole prophylaxis, and 42 primary
      caregivers, at a comprehensive HIV/AIDS clinic in Uganda, we evaluated their
      adherence experiences for purposes of program improvement. Daily drug regimens
      provided by the pediatric clinic included cotrimoxazole prophylaxis as well as
      ART and cotrimoxazole combined. Complete disclosure of HIV status by caregivers
      to children and strong parental relationships were related to good adherence.
      Structural factors including poverty and stigma were barriers to adherence even
      for children who had had complete disclosure and a supportive relationship with a
      parent. To ensure adherence to life-extending medications, our findings
      underscore the need for providers to support caregivers to disclose, provide on
      going support and maintain open communication with HIV-infected children taking
      cotrimoxazole prophylaxis and ART.

PMID- 16791526
TI  - An adolescent-targeted HIV prevention project using African professional soccer
      players as role models and educators in Bulawayo, Zimbabwe.
AB  - The calamitous effects of HIV in Africa demand novel approaches to prevention.
      Young people are an ideal target as early intervention may have long-term
      benefits. Given their high social status, professional soccer players may be
      effective in HIV education as role models and educators. In our study,
      professional soccer players provided HIV education in an interactive curriculum
      for 7th grade boys and girls in Bulawayo, Zimbabwe. Students in intervention
      classrooms demonstrated significant increases in knowledge and attitudes using
      pre-, immediately post- and five-month post-intervention surveys. There was a
      delayed increase in these factors among control students, suggesting a possible
      diffusion of information from their peers who received the intervention
      curriculum. Given these results and the magnitude of the HIV epidemic, this pilot
      program should be replicated in other communities in sub-Saharan Africa.
      Continual efforts should be made to rigorously evaluate the approach and improve
      its effectiveness.

PMID- 16791527
TI  - Perceptions of lifetime risk and actual risk for acquiring HIV among young men
      who have sex with men.
AB  - Among young men who have sex with men (MSM) surveyed in six US cities, we
      evaluated the magnitude and correlates of perceived lifetime risk for acquiring
      HIV, and missed opportunities to increase risk perception by providers of health
      care and HIV-testing services. Overall, approximately one quarter of young MSM
      perceived themselves at moderate/high risk for acquiring HIV. Adjusting for
      demographic, prior testing, and behavioral characteristics, moderate/high
      perceived risk had the strongest association with unrecognized HIV infection.
      However, half of the 267 young MSM with unrecognized infection perceived
      themselves at low lifetime risk for acquiring HIV, and many young MSM with low
      risk perception reported considerable risk behaviors. Providers of health-care
      and HIV-testing services missed opportunities to assess risks and recommend
      testing for young MSM. To increase HIV testing, prevention providers should
      intensify efforts to assess, and to increase when needed, perceptions of lifetime
      risks for acquiring HIV among young MSM.

PMID- 16791528
TI  - Ataques de nervios in relation to anxiety sensitivity among island Puerto Ricans.
AB  - This study investigated the symptom profile of ataques de nervios (ADN) among
      Puerto Rican volunteers from the community who self-identified as having
      experienced at least one ataque. As expected, the most commonly reported ataques
      specific symptoms were crying, anger, nervousness, and becoming hysterical.
      Comparing the responses of those with ADN to those with no history of ADN but who
      reported elevated anxiety sensitivity (AS) indicated that both groups were
      comparable on measures of depression, state and trait anxiety, and associated
      panic symptoms. As expected, both groups scored significantly higher on all
      measures than did participants with no history of ADN and low AS with the
      exception of the measure of state anxiety. It is unclear, however, whether the
      overlap in symptom severity between those with ADN and those with elevated
      anxiety sensitivity indicates that ADN and AS are the same or distinct
      conditions.

PMID- 16791529
TI  - Health care access and sociodemographic factors associated with hepatitis B
      testing in Vietnamese American men.
AB  - Chronic hepatitis B viral (HBV) infection greatly increases the risk for
      cirrhosis and hepatocellular carcinoma. HBV serologic testing is important for
      the identification of chronically infected individuals, who may benefit from
      antiviral treatment and regular monitoring for disease sequelae. Elevated rates
      of cirrhosis and hepatocellular carcinoma among Vietnamese American men can
      largely be attributed to high rates of chronic HBV infection. We surveyed 509
      Vietnamese men aged 18-64 years in Seattle, Washington and examined
      sociodemographic and health care access factors associated with HBV serology
      testing. Nearly two-thirds (65%) reported past testing. The following were among
      those factors associated with HBV testing in bivariate comparisons: older age;
      short proportion of life in the US; low English fluency; private health
      insurance; identifying a regular source of medical care; reporting no long waits
      for medical appointments; and having access to interpreter services. The
      following were independently associated with HBV testing in multiple logistic
      regression analysis: older age; college education; low English fluency; private
      health insurance; having a regular medical provider; and reporting no long waits
      for medical appointments. Younger and less educated men, and those with
      difficulty accessing medical care may be at particular risk for never having had
      HBV testing. Programs to reduce HBV transmission and sequelae should make special
      effort to target these vulnerable Vietnamese Americans.

PMID- 16791530
TI  - PTSD, depression, prescription drug use, and health care utilization of Chinese
      workers affected by the WTC attacks.
AB  - This study assessed the impact of the World Trade Center (WTC) attacks on
      emotional problems, prescription drug usage, and utilization of medical and
      mental health services within the Chinese community in lower Manhattan. We
      administered a survey to 148 randomly selected Chinese workers affected by the
      WTC attacks in March 2003. Although nearly half of the respondents had elevated
      PTSD and/or elevated depression scores, only a few (4.4%) had talked to a
      counselor. However, nearly all (86%) reported having visited a physician at least
      once since September 11, 2001. Individuals with elevated PTSD scores were
      significantly more likely to have gone to a physician after 9/11. They were also
      more likely to have received prescription drugs and to indicate an interest in
      counseling after 9/11 than individuals with low PTSD scores. The findings
      highlight the role of the primary care physician as gatekeeper for mental health
      symptoms after a disaster. They further suggest that primary care physicians
      should use screening tools for depression and posttraumatic stress after a major
      disaster and that they should be sensitive to potential emotional problems that
      are associated with somatic complaints.

PMID- 16791531
TI  - Breast and cervical cancer screening among South Asian women in New York City.
AB  - The purpose of this paper is to document the breast and cervical cancer screening
      practices of a community sample of South Asian women living in the New York City
      area. A convenience sample of 98 women was engaged in face-to-face interviews
      regarding their socio-demographic characteristics and cancer screening
      utilization. Sixty-seven percent of women had ever had a Pap test; 54% had one in
      the last 3 years. Seventy percent of women over 40 had ever had a mammogram; 56%
      had one in the last 2 years. Sixty-six percent of women had knowledge of breast
      self-exam (BSE); 34% of women ever practiced BSE. Multiple logistic regression
      analysis indicated that insurance status was a significant predictor of ever
      having a Pap test or mammogram, receiving timely Pap tests, and ever practicing
      BSE. Education was a significant predictor of ever having a Pap test and having
      knowledge of BSE. Marital status was a predictor of receiving timely Pap tests,
      and having spent more time in the U.S. was a predictor of ever practicing BSE.
      The study concludes that increased educational efforts must be developed
      targeting immigrant South Asian women of low socioeconomic status with limited
      access to healthcare.

PMID- 16791532
TI  - Factors of breast cancer screening among Korean immigrants in the United States.
AB  - The purpose of this paper is to assess breast cancer screening rates and explore
      factors related to all three measures of breast cancer screening, mammography,
      clinical breast examination (CBE), and breast self-examination (BSE), among
      Korean immigrants in the United States. A telephone survey was conducted with 189
      Korean women aged 40 and older in Cook County, Illinois. Of this group, 78% had
      had a mammogram at some point, and 38.6% had had one within the previous year.
      Fifty-three percent had had a CBE, while 26.1% had had one within the previous
      year. Whereas 58.1% had examined their breasts before, 46.3% did monthly BSE.
      Korean women's breast cancer screening rates are improving even though the rates
      are still lower than screening rates in the United States. Having a regular check
      up and being married were strongly related to all three measures of cancer
      screening. Further in-depth research is suggested to understand KA women's
      perspectives on having access to care.

PMID- 16791533
TI  - Correlates of breast cancer screening among Asian Americans enrolled in
      ENCOREplus.
AB  - This study examines the correlates of mammogram utilization among predominantly
      low income Asian American women using cross sectional data of women recruited
      through the ENCORE(plus) program (n = 1,695) between July 1996 and June 1998.
      Logistic regression was used to examine the independent effect of variables
      corresponding to Andersen's behavioral model of health services utilization on
      mammography screening behavior. Foreign-born women living in the U.S. < 5 years
      and between 5 and 10 years were significantly less likely to have ever had a
      mammogram than women who were born in the U.S. (OR 0.22; CI 0.12, 0.40 and OR
      0.48; CI 0.27, 0.86, respectively). Women 40-49 years old were half as likely to
      adhere to mammography screening recommendations as women 50-64 years (CI 0.33,
      0.76). Health insurance was positively associated with adherence to mammography
      screening guidelines (OR 1.59; CI 1.02, 2.48). The results of this study
      highlight the need for health education about breast cancer and mammography among
      Asian American women. Policy work also needs to be directed toward improving
      access to health care in this community.

PMID- 16791534
TI  - Reaching Asian Americans: sampling strategies and incentives.
AB  - Reaching and recruiting representative samples of minority populations is often
      challenging. This study examined in Chinese and Korean Americans: 1) whether
      using two different sampling strategies (random sampling vs. convenience
      sampling) significantly affected characteristics of recruited participants and 2)
      whether providing different incentives in the mail survey produced different
      response rates. We found statistically significant, however mostly not
      remarkable, differences between random and convenience samples. Offering monetary
      incentives in the mail survey improved response rates among Chinese Americans,
      while offering a small gift did not improve response rates among either Chinese
      or Korean Americans. This information will be useful for researchers and
      practitioners working with Asian Americans.

PMID- 16791535
TI  - Intimate partner violence associated with poor health outcomes in U.S. South
      Asian women.
AB  - To assess the associations between Intimate Partner Violence (IPV) victimization
      and health outcomes of South Asian women in Greater Boston. To explore the nature
      of the health experiences of victimized women in this population. Cross-sectional
      surveys with a community-based sample of women in relationships with males (n =
      208) assessed demographics, IPV history, and health. In-depth interviews were
      conducted with a separate sample of women with a history of IPV (n = 23).
      Quantitative data were assessed by logistic regression, qualitative data by a
      grounded theory approach. Twenty-one percent of the quantitative sample reported
      IPV in the current relationship. Abused women were significantly more likely than
      those with no history of IPV in their current relationship to report poor
      physical health (95% CI = 1.3-12.0), depression (95% CI = 1.8-9.3), anxiety (95%
      CI = 1.3-6.4), and suicidal ideation (95% CI = 1.9-25.1). Qualitative subjects
      described how victimization resulted in injury and chronic health concerns and
      how IPV-induced depression and anxiety affected their sleep, appetite, energy,
      and wellbeing. Experiences of IPV are related to increased poor health among
      South Asian women. This elevated risk demands intervention. Healthcare providers
      should be trained to screen and refer South Asian patients for partner violence.

PMID- 16791536
TI  - Sources of health information among Vietnamese American men.
AB  - Vietnamese American men face multiple health disparities compared to white men.
      Our study objective was to determine the sources of health information used by
      Vietnamese men in the United States. A population-based, in-person survey was
      conducted among Vietnamese men in Seattle during 2002. Our survey was completed
      by 509 Vietnamese men (79% response rate). The most commonly reported sources of
      health information included Vietnamese newspapers/magazines (73%), Vietnamese and
      English language television (64% and 67%, respectively), Vietnamese radio (51%),
      and friends and family members (51% and 63%, respectively). We found that sources
      of health information varied significantly among sociodemographic subgroups of
      the Vietnamese male population. Sources of health information among Vietnamese
      American men differ considerably from other racial/ethnic groups. Research
      findings should be used to guide the development of health education
      interventions for Vietnamese men and subgroups within the Vietnamese male
      population.

PMID- 16791537
TI  - Koreans' use of medical services in Seoul, Korea and California.
AB  - This study assessed the types of health care services used by Korean immigrants,
      and differences in use between different countries, genders, health insurance
      status, acculturation status, and cardiovascular risk. Participant selection used
      probability sampling to represent the adult populations of California, United
      States, and Seoul, Republic of Korea. A telephone survey was administered to
      2,830 adult Korean-Californians and 500 adult Koreans living in Seoul. Female
      gender was significantly associated with higher use of outpatient services, ER
      usage, and hospitalization. Californian residence was significantly associated
      with higher outpatient usage and lower hospitalization rates. Health insurance
      was associated with higher allopathic health care utilization, and lower
      traditional health care usage, and acculturation with lower traditional health
      care usage. Higher self-reported cardiac risk factors were associated with lower
      allopathic and higher traditional health care. This suggests barriers to
      allopathic health care, but not traditional health care, for Koreans living in
      California without health insurance.

PMID- 16791538
TI  - Higher mortality rate among infants of US-born mothers compared to foreign-born
      mothers in New York City.
AB  - This study is to compare infant mortality rates (IMRs) between US- and foreign
      born mothers in New York City. The linked live birth-infant death records from
      1995 to 1998 were analyzed. Overall US-born mothers had a higher IMR than foreign
      born mothers, though there were great variations in IMRs by country of maternal
      birth among foreign-born mothers. US-born mothers had higher IMRs compared to
      foreign-born mothers for several maternal/infant characteristics. Logistic
      regression analyses indicated that infants of foreign-born mothers were less
      likely to die from prematurity, Sudden Infant Death Syndrome and external causes,
      but were more likely to die of congenital anomalies than those of US-born
      mothers. Further analyses on the interactions of maternal race/ethnicity and
      country of birth showed variations in the IMRs of leading causes of death. Infant
      mortality reduction strategies should be differentially targeted to minority
      mothers of different countries of birth, particularly for potentially preventable
      causes of deaths.

PMID- 16791539
TI  - STI/HIV risks for Mexican migrant laborers: exploratory ethnographies.
AB  - The influx of Latino laborers into the U.S. and the confluence of migration
      driven factors in an environment ripe for risk-taking have the potential to
      exacerbate already rising STI/HIV rates among migrants and their social networks
      at both the home and receiving regions. This paper focuses on Mexican migrant
      laborers who are among the most marginalized and exploited Latinos in the U.S.
      This study used ethnographic methods to delineate the sociocultural and spatial
      contexts and social organization of migrant farmwork, and examined how
      intertwined individual and environmental factors render migrant farmworkers
      vulnerable to STI/HIV risks. Findings indicate the presence of a number of
      factors in the study population of Mexican migrant workers (N = 23)-such as
      poverty, limited education, physical/social/cultural isolation, long work hours,
      constant mobility, hazardous work conditions, limited access to health care, low
      rates of condom use, multipartnering, and use of sexworkers-which increase their
      risks for STI/HIV transmission. To be successful, prevention efforts need to
      focus not only on condom education and HIV awareness and testing, but also on
      reducing migrants' social isolation and understanding their social networks.

PMID- 16791540
TI  - Psychosis following acute Sydenham's chorea.
AB  - Sydenham's chorea (SC) is characterized by motor, mainly choreic involuntary
      movements, and psychiatric symptoms, including anxiety, depression, obsessive
      compulsive and attention-deficit/hyperactivity disorders. Symptoms of SC may be
      considered as the result of basal ganglia dysfunction determined by autoimmune
      mechanisms elicited by streptococcal infection. We report on a case of a 13-year
      old boy with brief psychotic episode following acute SC. His hallucinations and
      delusions remitted after treatment with risperidone, paralleling motor
      improvement. The neurobiological basis of psychotic symptoms remains largely
      elusive. This case report provides further insight about the involvement of basal
      ganglia dysfunction on psychosis.

PMID- 16791541
TI  - Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym
      XL with placebo in children with Attention Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: To compare the efficacy and safety of two methylphenidate (MPH)
      formulations--once-daily modified-release MPH (EqXL, Equasym XL) and twice-daily
      immediate-release methylphenidate (MPH-IR, Ritalin)--and placebo in children with
      Attention Deficit/Hyperactivity Disorder (ADHD). METHODS: Children aged 6-12
      years on a stable dose of MPH were randomized into a double-blind, three-arm,
      parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg
      qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR
      was assessed by the difference in the inattention/overactivity component of the
      overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per
      protocol population). Safety was monitored by adverse events, laboratory
      parameters, vital signs, physical exam, and a Side Effect Rating Scale. RESULTS:
      The lower 97.5% confidence interval bound of the difference between MPH groups
      fell above the non-inferiority margin (-1.5 points) not only during the last week
      of treatment but during all three treatment weeks. Both MPH-treatment groups
      experienced superior benefit when compared to placebo during all treatment weeks
      (P < 0.001). All treatments were well tolerated. CONCLUSIONS: EqXL given once
      daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior
      to placebo in reducing ADHD symptoms.

PMID- 16791542
TI  - Cognitive emotion regulation strategies and emotional problems in 9 - 11-year-old
      children: the development of an instrument.
AB  - The present study describes the development of the child version of the Cognitive
      Emotion Regulation Questionnaire (CERQ-k). Like the adult version of the CERQ,
      the CERQ-k measures nine cognitive emotion regulation strategies that children
      may use after having experienced negative life events. The original CERQ was
      considered suitable for adults and adolescents aged 12 and older. The CERQ-k was
      constructed for children of 9, 10 and 11 years of age. The present study
      describes some psychometric properties of the CERQ-k and relationships with
      measures of depression, fearfulness and worry among 717 primary school
      youngsters. Principal component analyses confirmed the allocation of most items
      to subscales, while Cronbach's alphas of most subscales exceeded 0.70. Cognitive
      emotion regulation strategies were found to be related to the reporting of
      symptoms of depression, fearfulness and worry, which provided some evidence for
      criterion-related validity.

PMID- 16791543
TI  - Electroconvulsive therapy (ECT) in a six-year-old girl suffering from major
      depressive disorder with catatonic features.
AB  - OBJECTIVE: ECT is generally both effective and safe in the treatment of
      adolescents, but treatment using ECT in children of pre-pubertal age has been
      less reported and is a controversial treatment. CLINICAL PICTURE: This article
      reports a 6-year-old girl who has been diagnosed as having major depressive
      disorder with catatonic features and 50% loss of weight due to food refusal.
      TREATMENT: The seven-session ECT treatment with bilateral and brief pulse
      stimulation was successfully done. Propofol 1% was used for anesthesia. OUTCOME:
      After the third session, the patient's clinical improvement began by eating. As
      the ECT sessions went on the signs of depression and catatonic features
      completely resolved. There were no noticeable clinical side effects. CONCLUSION:
      ECT should be considered in severe cases of child psychiatric disorders where it
      is life threatening, as an effective and safe method.

PMID- 16791544
TI  - Realistic assessment of the physician-staffed emergency services in Germany.
AB  - In Germany the emergency medical services, which include dispatching emergency
      physicians to the scene, are considered to be among the best in the world.
      However, the hospitals admitting these patients still report shortcomings in
      prehospital care. The quality of an emergency medical service depends on both
      formal qualification and experience in managing such emergencies. Therefore, we
      determined how frequently emergency medical service physicians in Germany
      actually encountered complex and demanding emergency situations outside the
      hospital and how often they had to carry out emergency interventions. We
      therefore evaluated data from more than 82,000 ground emergency medical service
      scene calls registered in the MIND ("minimaler Notarztdatensatz") data base of
      the state of Baden-Wuerttemberg, Germany and more than 47,000 helicopter
      emergency medical service scene calls from the "Luftrettungs-, Informations- und
      Kommunikationssystem" (LIKS) data base of the German ADAC air rescue service. The
      results, which were unexpectedly distinct, impressively demonstrate that in part
      emergency medical service staff only encountered some emergencies very rarely. In
      particular, patients with life-threatening conditions such as acute coronary
      syndrome, stroke, head trauma, as well as multiple trauma were only treated once
      every 0.4-14.5 months and cardiopulmonary resuscitation and intubation were only
      carried out once every 0.5-1.5 months. Furthermore, a time period of 6 months to
      more than 6 years may pass before a chest tube has to be placed. There are, of
      course, considerable differences between ground and helicopter emergency medical
      services. Particularly in areas where the frequency of such emergency cases is
      low, the clinical experience required to competently manage a demanding emergency
      situation cannot be gained or maintained just by working in the emergency medical
      system. As a result of the general pressure to cut costs and also of changes in
      hospital politics, however, only highly qualified and experienced emergency
      medical services may survive in Germany in the long term. In addition to formal
      qualifications and accompanying practice-related courses, future emergency
      medical service personnel should be drafted from clinical department staff that
      are experienced in treating severely ill and severely injured patients.

PMID- 16791545
TI  - [Current level of patients' knowledge of anaesthesiology].
AB  - The anaesthesiologist's competence in anaesthesia, intensive care medicine, pain
      therapy and emergency medicine is accepted throughout the medical society.
      Nevertheless, during the last decades patient surveys demonstrated a considerable
      lack of information of the responsibility of our work. By continuous education
      and information anaesthesiologists have aimed to improve the information and
      decision-making process for the patient. This multicentre trial was designed to
      investigate the current public view on our profession in seven German hospitals.
      In-hospital patients were asked to fill out a standardised questionnaire prior to
      the anaesthesia premedication visit and a total of 692 questionnaires (77%) were
      analysed. Results demonstrated an increased level of knowledge for anaesthesia
      (>95%), intensive care medicine (74%), and pain therapy (50% acute pain; 32%
      severe pain). In the case of emergency medicine (10%) the in-hospital and out-of
      hospital responsibilities were not clear among patients. We conclude that the
      continuous distribution of information in recent years has contributed to
      improving patients' knowledge on interdisciplinary responsibilities. Future
      efforts should focus on the gaps in patient's knowledge to allow the patient to
      ask the right questions necessary for decision-making.

PMID- 16791546
TI  - [Introductory report of the Central Ethics Commission for Stem Cell Research].

PMID- 16791547
TI  - [Antidepressants and suicidality. Risk-benefit analysis].
AB  - Reanalyses of placebo-controlled trials reveal an increased risk of suicidal
      ideations or parasuicidal acts in children and adolescents under treatment with
      selective serotonin reuptake inhibitors (SSRI) or other antidepressants. Although
      no completed suicide was shown, these findings are the more important because,
      with the exception of fluoxetine, an evidence base for the efficacy of
      antidepressants is weak or lacking in this age group. For adults, there is no
      reason to doubt that antidepressants help to reduce suicides by shortening
      depressive episodes and preventing recurrence. A general and pronounced suicide
      inducing effect of SSRI or other antidepressants can largely be excluded. On the
      other hand, in some vulnerable patients the risk of suicidal acts can increase,
      especially during the first days of antidepressant treatment. There is no
      evidence that this risk is higher with SSRI than with other antidepressants or
      nonpharmacological treatments. Safety in case of overdose is a strong argument
      favouring newer antidepressants over tri- and tetracyclic antidepressants in
      outpatients with unclear suicidality. The current widespread public discussions
      concering the risks of antidepressants is a risk in itself because confidence in
      treatment, compliance, and help seeking behaviour may get influenced negatively.

PMID- 16791548
TI  - [Applicability, duration, and sociomedical course of rehabilitation of alcohol
      dependency. Current results and perspectives from the insurers' point of view].
AB  - Reducing the paucity of German studies on the rehabilitation of alcohol-dependent
      patients, this article presents current data of Germany's national Pension
      Insurance Federal Institution. Numbers of applications, grants and use of
      rehabilitation, length and duration of treatment, percentage of nonattendance,
      comorbidity, and sociomedical course after 2 years are discussed. There has been
      a constant increase in numbers of rehabilitative treatment, especially in the
      outpatient setting with decreased treatment length, a high rate of comorbidity,
      and improvements in the sociomedical course and vocational integration. Two years
      after rehabilitation, 87% of inpatients and 92% of outpatients were
      recontributing to the pension system continuously or sporadically. Despite the
      still marked deficits in the provision of rehabilitative treatment for addicted
      patients, rehabilitation plays an important and established role in this field
      and shows promising clinical results.

PMID- 16791549
TI  - [The Six Factor Test--a personality questionnaire for clinical practice and
      research].
AB  - BACKGROUND: The Six factor Test (SFT) is a personality questionnaire for
      assessment of the "big five" (neuroticism, extraversion, conscience,
      aggressivity, openness to experiences) and piety in patients with mental
      disorders and healthy subjects. METHODS: In a study of 360 probands (125
      depressive and bipolar patients, 150 first-degree relatives of these patients,
      and 85 controls), the reliability and validity of the SFT was examined. Thirty
      five controls and 79 relatives were reinvestigated after around 6.5 years.
      RESULTS: The factorial structure could be replicated, and the concurrent validity
      was moderate to high. Acceptable internal consistency was observed, with the
      exceptions of "openness" and "agreeableness". The retest reliability was high,
      with the exception of "openness". Patients differed from controls in neuroticism
      and "openness". These factors were also predictive for the first onset of
      psychiatric disorders in controls and relatives, respectively. CONCLUSION: The
      SFT is a short und simple instrument for the assessment of personality in
      clinical samples and controls. Reliability and validity of the three main scales
      (neuroticism, extraversion, and conscience) were acceptable. The corresponding
      coefficients of the three shorter scales, in particular of openness, were partly
      much lower.

PMID- 16791550
TI  - [Expenditures in psychiatric treatment].

PMID- 16791551
TI  - Evaluation of commercial immunoassays for the detection of estrogens in water by
      comparison with high-performance liquid chromatography tandem mass spectrometry
      HPLC-MS/MS (QqQ).
AB  - In this work four different commercially available enzyme-linked immunosorbent
      assays (ELISA) (from Japan EnviroChemicals, Ltd., Tokyo, Japan) were evaluated in
      terms of performance for the rapid screening of estrogens in different water
      matrices, including natural and spiked samples from urban wastewater, river water
      and ground water. All four test kits are based on monoclonal antibodies. The
      compounds detected by these immunoassays are (1) 17-beta-estradiol, (2) estrone,
      (3) 17-alpha-ethynyl estradiol and (4) estrogens in general, with high
      recognition properties for 17-beta-estradiol, estrone and estriol. Standards were
      prepared in water containing 10% (v/v) methanol. The IC50 (corresponding to the
      50% of the effective concentration) values, the dynamic ranges, and the limits of
      detection of the ELISA kits were 0.060-0.304 microg/L, 0.05-5 microg/L and 0.05
      microg/L, respectively. All samples were extracted by solid-phase extraction
      (SPE) beforehand, and the evaluation was carried out by comparing the results
      obtained by ELISA with those obtained by HPLC-MS/MS using a triple quadrupole
      (QqQ) instrument. In addition, two different solid-phase extraction procedures
      were carried out and compared. Except for moderate overestimation in the results
      observed with the ELISA kits in the analysis of complex wastewater samples, the
      results obtained using all of the tested techniques were generally in very good
      agreement.

PMID- 16791552
TI  - Acidity constants in different media (I=0 and I=0.1 M KCl) from the uncertainty
      perspective.
AB  - Procedures for estimating the measurement uncertainty for the acidity constant Ka
      (or the pKa value) in different media (I=0 and I=0.1 mol L(-1) KCl), as
      determined by potentiometric titration, are presented. The uncertainty budgets
      (the relative contributions of the different input quantities to the uncertainty
      in the result) of the pKa (I=0) and pKa (I=0.1 mol L(-1) KCl) values are
      compared. Unlike the values themselves, the uncertainties and uncertainty budgets
      of the values are comparable. The uncertainty estimation procedures are based on
      mathematical models of pKa measurement and involve the identification and
      quantification of individual uncertainty sources according to the ISO GUM
      approach. The mathematical model involves 52 and 48 input parameters for pKa
      (I=0) and pKa (I=0.1 mol L(-1) KCl), respectively. The relative importance of
      each source of uncertainty is discussed. In both cases, the main contributors to
      the uncertainty budget are the uncertainty components due to the hydrogen ion
      concentration/activity measurement, which provide 63.7% (for pKa (I=0)) and 89.3%
      (for pKa (I=0.1 mol L(-1) KCl)) of the uncertainty. The remaining uncertainty
      contributions arise mostly from the limited purity of the acid. From this work,
      it is clear that the uncertainties of the pKa (I=0.1 mol L(-1) KCl) values tend
      to be lower than those of the pKa (I=0) values. The main reasons for this are
      that: (1) the uncertainty due to the residual liquid junction potential is
      nominally absent in the case of pKa (I=0.1 mol L(-1) KCl) due to the similarly
      high concentrations of background electrolyte in the calibration solutions and
      measured solution; (2) the electrode system is more stable in solutions
      containing the 0.1 mol L(-1) KCl background electrolyte and so the readings
      obtained in these solutions are more stable.

PMID- 16791553
TI  - Recent developments in microarray-based enzyme assays: from functional annotation
      to substrate/inhibitor fingerprinting.
AB  - Recent advances in proteomics have provided impetus towards the development of
      robust technologies for high-throughput studies of enzymes. The term "catalomics"
      defines an emerging '-omics' field in which high-throughput studies of enzymes
      are carried out by using advanced chemical proteomics approaches. Of the various
      available methods, microarrays have emerged as a powerful and versatile platform
      to accelerate not only the functional annotation but also the substrate and
      inhibitor specificity (e.g. substrate and inhibitor fingerprinting, respectively)
      of enzymes. Herein, we review recent developments in the fabrication of various
      types of microarray technologies (protein-, peptide- and small-molecule-based
      microarrays) and their applications in high-throughput characterizations of
      enzymes.

PMID- 16791554
TI  - Building a professional career. Common sense is not common.

PMID- 16791556
TI  - Solution to quality assurance challenge 3.

PMID- 16791558
TI  - A new time-resolved fluorometric microarray detection system using core-shell
      type fluorescent nanosphere and its application to allergen microarray.
AB  - We have developed a new time-resolved fluorometric (TRF) microarray detection
      system consisting of fluorescent NH2 nanosphere, TRF microarray detector and
      gamma-irradiated polystyrene chip. Using the TRF microarray detector, we detected
      500 particles of the fluorescent nanosphere in one channel. Cross-talk
      fluorescence from the adjacent channels was little observed in the TRF microarray
      detector (<0.0004 %). The TRF microarray detection system was further applied for
      serum allergen-specific immunoglobulin E (IgE) multi-analyses. As a labeled tag
      antibody, an anti-human IgE Fab' fragment-conjugated fluorescent nanosphere (Fab'
      nanosphere) was prepared as described previously. As a chip surface appropriate
      for allergen immobilization, the polystyrene chip surface was modified by gamma
      irradiation. The immunoassay reactivity using the gamma-irradiated polystyrene
      chip was approximately 2.5-times improved compared with that of the non-treated
      polystyrene chip. Non-specific adsorption of the Fab' nanosphere onto the gamma
      irradiated polystyrene chip surface was very low level (<0.0009 %). In only 20
      mul of serum, six allergen-specific IgEs could be simultaneously determined in
      one reaction well in fewer than 90 min. Good correlation curves were obtained
      between the microarray immunoassay and the CAP RAST fluoro-enzyme immunoassay
      (CAP/RAST FEIA) method (r > 0.961). Reproducibility (CVs) of the microarray
      immunoassay was 8.6 % to 19.0 % (n = 5).

PMID- 16791560
TI  - Pretreatment and one-shot separating analysis of whole catecholamine metabolites
      in plasma by using LC/MS.
AB  - Catecholamines are biogenic amines that play an important role in the nervous
      system. Some catecholamines have been used as tumor makers of phenochromocytoma,
      paraganglioma and neuroblastoma. The analysis of total catecholamine metabolites
      should be useful for one-shot screening of multiple aspects of diseases; however,
      it is difficult to do this, because the catecholamine metabolites are divided
      into three groups: five amines, one amino acid and three carbonic acids.
      Catecholamines and small molecules were separated from plasma proteins by an
      internal-surface reversed-phase column (protein-coated octadeyclsilica column)
      and were analyzed by liquid chromatography (LC)/mass spectrometry (MS) using
      electrospray ionization time-of-flight MS. Using a reversed-phase column and
      hydrophilic mobile phases, we succeeded in the separation of nine catecholamines,
      all of which had similar structures. These nine substances were eluted in the
      following order: norepinephrine, epinephrine, normetanephrine, dopamine,
      metanephrine, 3,4-dihydroxyphenylalanine, vanillomandelic acid, 3,4
      dihydroxyphenylacetic acid and homovanillic acid. The reproducibility of this
      method was acceptable. The highest coefficient of variation was 7.4%. In
      addition, various types of compounds were separated from and detected in plasma
      proteins by applying LC/MS. The plasma direct injection method, which uses an
      internal-surface reversed-phase column and an ion-pair reagent, allowed us to
      separate small molecules from plasma proteins. MS detected some compounds that
      high-performance LC could not succeed in separating and detecting with UV
      detection. We think that the method can be applied to find new markers in
      neuroblastoma, by comparing the plasma of patients with that of normal infants.
      The method can be also used to help in making a diagnosis of other diseases and
      finding their new makers.

PMID- 16791559
TI  - ClcR-based biosensing system in the detection of cis-dihydroxylated (chloro
      )biphenyls.
AB  - Polychlorinated biphenyls (PCBs) are a group of organic pollutants that are
      persistent when released into the environment. Among the metabolites of PCBs,
      dihydroxylated PCBs are also considered as toxic compounds. Various studies have
      shown that dihydroxylated PCBs affect the reproductive, immune, nervous, and
      endocrine systems. Detection of these chemicals in environmental and biological
      samples could provide first-hand information about their levels and lead to a
      better understanding of their role in toxicity. To that end, we developed a
      sensing system for the detection of dihydroxylated PCBs based on the clc operon.
      The Pseudomonas putida clc operon encodes a catabolic pathway for degradation of
      chlorocatechols, which are major metabolites of a large number of chlorinated
      compounds. In P. putida, the expression of these genes is regulated by a protein
      encoded by the gene clcR located upstream from the clcABD genes. We demonstrate
      here for the first time that dihydroxy PCBs can also induce the clc operon. Our
      sensing system employs P. putida bacteria harboring a plasmid in which the
      reporter gene, lacZ, is under the control of the regulatory protein ClcR.
      Consequently, when exposed to dihydroxy PCBs, the bacteria express beta
      galactosidase in an amount related to the concentration of the corresponding
      dihydroxy PCB. Various dihydroxylated PCBs, differing in the number and position
      of chlorines and in the position of hydroxyls, were tested for their ability to
      induce expression of beta-galactosidase. Detection limits as low as 1 x 10(-6)
      mol L(-1) were obtained for various dihydroxylated PCBs.

PMID- 16791561
TI  - Mass spectrometric identification and characterization of antimony complexes with
      ribose-containing biomolecules and an RNA oligomer.
AB  - Mass spectrometric techniques have been used to study the interaction of
      inorganic Sb(V) with biomolecules containing a ribose or deoxyribose moiety.
      Electrospray (ES) mass spectra of reaction mixtures containing inorganic Sb(V)
      and one of several biomolecules (adenosine, cytidine, guanosine, uridine,
      adenosine-5'-monophosphate, adenosine-3',5'-cyclic monophosphate, ribose, or 2'
      deoxyadenosine) afforded high-mass antimony-containing ions corresponding to
      Sb(V)-biomolecule complexes of stoichiometry 1:1, 1:2, or 1:3. The complexes were
      characterized by collision-induced dissociation (CID) tandem mass spectrometry
      (MS) using ion-trap multistage MS. The CID results revealed that Sb(V) binds to
      the ribose or deoxyribose moiety. Structures are proposed for the Sb-biomolecule
      complexes. Analysis of the reaction mixtures by reversed-phase chromatography
      coupled on-line to either inductively coupled plasma (ICP) MS or ES-MS showed
      that in solution Sb(V) forms complexes with all the analyzed biomolecules with
      vicinal cis hydroxyl groups. Evidence (from size-exclusion chromatography ICP-MS
      and direct infusion ES-MS) of complexation of Sb(V) with an RNA oligomer, but not
      with a DNA oligomer, supports the suggestion that the presence of vicinal cis
      hydroxyl groups is critical for complexation to occur. This is the first direct
      evidence of complexation of Sb(V) with RNA. Results obtained by studying the
      effect of changing reaction conditions, i.e. pH, reaction time, and
      Sb/biomolecule molar ratio, on the extent of Sb-biomolecule formation suggest the
      reaction may be of physiological importance. Selected reaction monitoring (SRM)
      and precursor-ion-scanning tandem MS were investigated to determine their
      potential to detect trace levels of the Sb-biomolecule complexes in biological
      samples. Application of SRM MS-MS in combination with high-performance liquid
      chromatography enabled successful detection of an Sb-adenosine complex that had
      been spiked into a complex biological matrix (liver homogenate).

PMID- 16791562
TI  - 31P NMR study on the autophosphorylation of insulin receptors in the plasma
      membrane.
AB  - A nonradioactive 31P nuclear magnetic resonance (NMR) spectroscopy protocol has
      been developed and used to investigate in vitro autophosphorylation of insulin
      receptors. Optimum experimental conditions have been explored, and the effects of
      Mn2+ and phosphocreatine (PCr) on the determination of the phosphorylation
      reaction have been assayed. The method was used to monitor the time courses of
      the phosphorylation reaction in solution. The results from this NMR study were in
      agreement with observations of insulin receptor phosphorylation made by using
      Western blotting.

PMID- 16791563
TI  - Capillary isoelectric focusing of microorganisms in the pH range 2-5 in a
      dynamically modified FS capillary with UV detection.
AB  - The isoelectric points of many microbial cells lie within the pH range spanning
      from 1.5 to 4.5. In this work, we suggest a CIEF method for the separation of
      cells according to their isoelectric points in the pH range of 2-5. It includes
      the segmental injection of the sample pulse composed of the segment of the
      selected simple ampholytes, the segment of the bioanalytes and the segment of
      carrier ampholytes into fused silica capillaries dynamically modified by
      poly(ethylene glycole). This polymer dissolved in the catholyte, in the anolyte
      and in the injected sample pulse was used for a prevention of the bioanalyte
      adsorption on the capillary surface and for the reduction of the electroosmotic
      flow. Between each focusing run, the capillaries were washed with the mixture of
      acetone/ethanol to achieve the reproducible and efficient CIEF. In order to trace
      of pH gradients, low-molecular-mass pI markers were used. The mixed cultures of
      microorganisms, Escherichia coli CCM 3954, Candida albicans CCM 8180, Candida
      parapsilosis, Candida krusei, Candida glabrata, Candida tropicalis, CCM 8223,
      Proteus vulgaris, Klebsiela pneumoniae, Staphylococcus aureus CCM 3953,
      Streptococcus agalactiae CCM 6187, Enterococcus faecalis CCM 4224 and
      Staphylococcus epidermidis CCM 4418, were focused and separated by the CIEF
      method suggested here. This CIEF method enables the separation and detection of
      the microbes from the mixed cultures within several minutes. The minimum
      detectable number of microbial cells was less than 10(3).

PMID- 16791564
TI  - Method for homogeneous spotting of antibodies on membranes: application to the
      sensitive detection of ochratoxin A.
AB  - Membrane-based dot immunoassays are now widely used in almost every branch of
      biology and medicine. However, the quality of the immobilized antigen or antibody
      spots on the membranes was found to be highly operator-dependent and spotting by
      conventional methods often leads to heterogeneous spot morphologies and
      deposition inconsistencies. To circumvent these problems, a spotting method has
      been developed which is based on focussed absorption of an applied antibody
      solution through an aqueous network of capillary channels formed between the
      membrane and a wetted absorbent body. The method does not require any equipment
      for creating vacuum and according to assay requirements highly homogeneous spots
      of uniform size, in the range of 0.8- to 9-mm diameter, can be obtained by
      varying the volume of the applied antibody solution. Spot intensities were
      sufficiently high even at high antibody dilutions. Immobilization of anti
      ochratoxin A (anti-OA) antibody by this method gave 2-fold increased sensitivity
      in a competitive assay of the toxin compared to conventional spotting methods.
      The calculated CV of the colour intensity for spots of different sizes (0.8 to 9
      mm) was between 4.5 and 1%. Application of this spotting technique has been
      demonstrated for detection of OA in wine and coffee samples with the elimination
      of matrix interferences in the same immunoassay system. This was achieved by
      selective removal of nonspecific interfering substances from the sample extract
      during the assay. The detection limit of OA in wine (1 microg L(-1)) and coffee
      (2.5 microg kg(-1)) obtained by the present new method is superior to values
      reported recently. Thus, the present new method will be highly useful for
      improved performance of membrane-based immunoassays in almost every branch of
      biology and medicine.

PMID- 16791565
TI  - Analysis of urine for cysteine, cysteinylglycine, and homocysteine by high
      performance liquid chromatography.
AB  - A new analytical method is proposed for simultaneous determination, by liquid
      chromatography, of the three main urinary thiols-cysteine, cysteinylglycine, and
      homocysteine. To measure the total amount of these thiols urine is reduced with
      sodium borohydride, to convert disulfides to thiols which are then derivatized
      with 2-chloro-1-methylquinolinium tetrafluoroborate. Separation and quantitation
      of the 2-S-quinolinium thiol derivatives formed were achieved by high-performance
      liquid chromatography with detection at 355 nm. Validation showed the method
      enabled reliable simultaneous determination of these aminothiols in urine. The
      calibration graphs for each analyte, obtained by use of normal urine spiked with
      increasing amounts of cysteine, cysteinylglycine, and homocysteine, were linear
      (R2 > or = 0.997) over the range covering most practical situations. The recovery
      of the assay was 98-100% and sensitivity was 0.12-0.25 micromol L(-1). The method
      was applied to 91 different samples of normal urine to establish reference values
      for the aminothiols, normalized on creatinine.

PMID- 16791566
TI  - Highly sensitive spectrofluorimetric determination of trace amounts of lecithin.
AB  - A new spectrofluorimetric method was developed for the determination of trace
      amounts of lecithin using the ciprofloxacin (CIP)-terbium (Tb3+) ion complex as a
      fluorescent probe. In a buffer solution at pH = 5.60, lecithin can remarkably
      reduce the fluorescence intensity of the CIP-Tb3+ complex at lambda = 545 nm. The
      reduced fluorescence intensity of the Tb3+ ion is proportional to the
      concentration of lecithin. Optimum conditions for the determination of lecithin
      were also investigated. The linear range and detection limit for the
      determination of lecithin were 1.0 x 10(-6) - 3.0 x 10(-5) mol L(-1) and 3.44 x
      10(-7) mol L(-1), respectively. This method is simple, practical, and relatively
      free of interference from coexisting substances. Furthermore, it has been
      successfully applied to assess lecithin in serum samples.

PMID- 16791567
TI  - Feasibility of preparing and analyzing gas standards containing heavy
      hydrocarbons (C10-C16).
AB  - State and federal agencies are beginning to monitor ambient air for compounds
      related to diesel exhaust. The National Institute of Standards and Technology
      (NIST) was asked to develop standards containing heavy (C10-C16) alkanes which
      could then be used in air monitoring and exhaust studies. Several primary
      gravimetric standards, containing heavy (C10-C16) alkanes in nitrogen, were
      developed and analyzed by gas chromatography (GC) with flame-ionization detection
      (FID). The results of this research indicate that accurate gas standards
      containing these hydrocarbons can be prepared. However, the analytical results
      show that the temperature of the transfer system from the gas cylinder to the GC
      column (including the gas-sample valve) must be heated in order to prevent
      adsorption of these compounds within the analytical system. The results indicate
      that even at elevated temperatures these compounds are being absorbed within the
      system. The results show that quantitative results cannot be obtained by using
      one compound such as hexane, as an internal standard to determine the
      concentration of other hydrocarbons. Quantitative and accurate results are best
      obtained if standards for each hydrocarbon of interest are used to determine
      concentrations of unknowns for the respective hydrocarbon.

PMID- 16791568
TI  - SPE-HPLC purification of endocrine-disrupting compounds from human serum for
      assessment of xenoestrogenic activity.
AB  - Assessment of xenoestrogenic activity in human serum samples requires the removal
      of endogenous sex hormones to assure that the activity measured originates from
      xenobiotic compounds only. Serum samples representing high, medium and lower
      accumulation of persistent organic pollutants (POPs) were extracted using solid
      phase extraction (SPE) followed by normal-phase high-performance liquid
      chromatography (NP-HPLC) for separation of POPs from endogenous hormones. The
      recovery of polychlorinated biphenyl (PCB) congeners in spiked serum samples was
      up to 86 %, making the extraction method suitable for the study. MVLN cells,
      stably transfected with an estrogen receptor (ER) luciferase reporter vector
      (estrogen response element chemically activated luciferase expression, ERE
      CALUX), were exposed to the reconstituted SPE-HPLC extracts for determination of
      the integrated estrogenic activity. The effects of PCBs were analyzed by direct
      in vitro exposure of PCBs (nos. 138, 153, 180) and by ex vivo analysis of SPE
      HPLC extracts from serum spiked with the PCBs. Similar effects on ER
      transactivation were observed for the direct in vitro and the ex vivo analysis
      experiments. The ER transactivation responses determined for actual serum samples
      were in the linear range of the dose-response curve. 17beta-Estradiol titrations
      showed that the xenoestrogenic effects were mediated via ER. Moreover, our SPE
      HPLC-ERE-CALUX assay was demonstrated to elicit high interlaboratory correlation.
      In the present study the combination of SPE-HPLC purification and the ex vivo
      estrogenic responses measured by ERE-CALUX was validated and considered to be a
      valuable tool to assess the combined ER effect of lipophilic serum POPs where
      additive/synergistic and agonistic/antagonistic effects are integrated giving an
      overall estimate of exposure and bioactivity.

PMID- 16791569
TI  - Powerful preconcentration method for capillary electrophoresis and its
      application to analysis of ultratrace amounts of polycyclic aromatic
      hydrocarbons.
AB  - For environmental analyses, a high-performance and powerful preconcentration
      system exceeding 1 x 10(7)-fold was developed that was composed of a blue cotton
      method (solid extraction method)/homogeneous liquid-liquid extraction method/on
      line concentration method for capillary electrophoresis (CE). This system was
      named the "triplex concentration system" and it was achieved by finding a new
      phase-separation phenomenon (homogeneous liquid-liquid extraction) from a water
      miscible organic solvent. Parts per trillion levels of polycyclic aromatic
      hydrocarbons (PAHs) were used as model analytical targets in this study. With the
      proposed method, 20-L levels of environmental water could be preconcentrated up
      to 1 x 10(7)-fold within a maximum of 1 h. The parts per trillion levels of PAHs
      were easily determined even using UV/CE, which has a serious sensitivity problem,
      and the detection limit of benzo[a]pyrene was 3.60 ppt. This system was also used
      as a practical monitoring method for the Miyata River (in Japan).

PMID- 16791570
TI  - UV/Vis spectra and solubility of some naphthoquinones, and the extraction
      behavior of plumbagin from Plumbago scandens roots in supercritical CO2.
AB  - The solubility of 1,4-naphthoquinone, plumbagin, lawsone, and juglone in
      supercritical carbon dioxide was determined spectroscopically at 40 degrees C,
      and in the pressure range 8-18 MPa. Their solubilities at 12 MPa were between 0.3
      and 10 g L(-1). Plumbagin from Plumbago scandens L. roots was extracted at 40
      degrees C and 20 MPa. The extracted plumbagin mass fraction was up to 0.2% in
      fresh roots but down to about 0.006% in aged roots. n-Hexane and chloroform
      extraction of such aged roots indicates that the older and dryer the roots are,
      the stronger they bind plumbagin. Reversed-phase HPLC indicated a relatively pure
      plumbagin extract with supercritical carbon dioxide.

PMID- 16791571
TI  - Microwave-assisted solvent extraction and gas chromatography ion trap mass
      spectrometry procedure for the determination of persistent organochlorine
      pesticides (POPs) in marine sediment.
AB  - Microwave-assisted solvent extraction of persistent organochlorine pesticides
      (POPs) in marine sediment was developed and optimized by means of two-level
      factorial designs. Six variables (microwave power, extraction time and
      temperature, amount of sample, solvent volume, and sample moisture) were
      considered as factors in the optimization process. The results show that the
      amount of sample to be extracted and solvent volume are statistically significant
      for the overall recovery of the studied pesticides, although compromise
      conditions have to be established with the object of avoiding overpressure in
      closed vessels. After extraction, a clean up step including the use of a silica
      cartridge was performed prior to chromatographic determination in order to remove
      interferences. The optimized procedure was compared to conventional Soxhlet
      extraction. The MS-MS ion preparation mode was applied to improve the sensitivity
      and selectivity of the chromatographic technique.

PMID- 16791572
TI  - Ultrasound-assisted extraction of pesticides from olive branches: a
      multifactorial approach to method development.
AB  - A rapid and simple method has been developed for the analysis in olive branches
      of two insecticides currently used in olive pest control, dimethoate and alpha
      cypermethrin. The effects of analytical conditions on pesticide recovery and the
      optimal extraction conditions were evaluated by means of a factorial design. The
      use of this chemometric tool in analytical method development allows the
      identification of the principal and interaction effects of the extraction
      conditions on the recovery of pesticides. It also gives information about the
      location of pesticide maximum recovery with minimal experimental investment.
      Extraction was carried out with an ultrasonic bath and the experimental
      conditions studied included the volume of extractant, the time of extraction, the
      number of extraction steps and the sample weight. The sample was further cleaned
      up using a Florisil solid-phase extraction cartridge. For the overall extraction
      procedure, recoveries of 99 % for alpha-cypermethrin and 90 % for dimethoate from
      the spiked samples were found for 1 g of sample extracted three times with 35 mL
      hexane, sonicating for 2 min in each step. The complete process including
      ultrasonic extraction and filtration will not require more than 15-20 min, in
      contrast with several hours for conventional liquid-solid extraction techniques.
      The proposed method allows a high sample throughput, as commonly required in
      monitoring studies.

PMID- 16791573
TI  - A novel thiocyanate-selective electrode based on a zinc-phthalocyanine complex.
AB  - A novel thiocyanate (SCN-)-selective PVC membrane electrode based on a zinc
      phthalocyanine (ZnPc) complex as neutral carrier is described. The membrane
      electrode containing ZnPc with 5.1% (w/w) ionophore, 29.2% (w/w) PVC, and 65.7%
      (w/w) 2-nitrophenyl octyl ether (o-NPOE) as plasticizer displayed an anti
      Hofmeister selectivity sequence, SCN- > Sal- > I- > ClO4- > Br- > Cl- > NO3- >
      NO2- > H2PO4- > SO4(2-)), and exhibited near-Nernstian potential response to
      thiocyanate ranging from about 1.0 x 10(-1) to 1.0 x 10(-6) mol L(-1) with a
      detection limit of 7.5 x 10(-7) mol L(-1) and a slope of 58.1+/-0.5 mV per decade
      in pH 3.0 phosphate buffer solution at 25 degrees C. This preferential response
      is believed to be associated with the unique coordination between the central
      metal of the carrier and thiocyanate.

PMID- 16791574
TI  - Combining visible and near-infrared spectroscopy with chemometrics to trace
      muscles from an autochthonous breed of pig produced in Uruguay: a feasibility
      study.
AB  - Visible (Vis) and near-infrared reflectance (NIR) spectroscopy combined with
      chemometrics was explored as a tool to trace muscles from autochthonous and
      crossbreed pigs from Uruguay. Muscles were sourced from two breeds, namely, the
      Pampa-Rocha (PR) and the Pampa-Rocha x Duroc (PRxD) crossbreed. Minced muscles
      were scanned in the Vis and NIR regions (400-2,500 nm) in a monochromator
      instrument in reflectance. Principal component analysis (PCA), discriminant
      partial least square regression (DPLS), linear discriminant analysis (LDA) based
      on PCA scores and soft independent modelling of class analogy (SIMCA) were used
      to identify the origin of the muscles based on Vis and NIR data. Full cross
      validation was used as validation method when classification models were
      developed. DPLS correctly classified 87% of PR and 78% of PRxD muscle samples.
      LDA calibration models correctly classified 87 and 67% of muscles as PR and PRxD,
      respectively. SIMCA correctly classified 100% of PR muscles. The results
      demonstrated the usefulness of Vis and NIR spectra combined with chemometrics as
      rapid method for authentication and identification of muscles according to the
      breed of pig.

PMID- 16791575
TI  - Determination of volatile oak compounds in aged wines by multiple headspace solid
      phase microextraction and gas chromatography-mass spectrometry (MHS-SPME-GC-MS).
AB  - Multiple headspace solid-phase microextraction (MHS-SPME) with gas chromatography
      mass spectrometry is proposed for quantification of nine volatile oak compounds
      in aged wines. These compounds are formed and extracted by wine when it is
      matured in oak barrels and are responsible for particular organoleptic properties
      and the high quality of these wines. Some important variables of the extraction
      process, for example volume of sample and extraction time, were studied.
      Extraction of 50 microL wine was performed with a divinylbenzene-Carboxen
      polydimethylsiloxane fibre at 55 degrees C for 60 min. For calibration the same
      conditions were used, except that the wine was substituted by 50 microL of a
      standard solution in synthetic wine. The linearity, detection limits, and
      repeatability of the method were determined by use of standard solutions in
      synthetic wine. Detection limits were between 0.01 and 10 microg L(-1) (for
      eugenol and furfural, respectively) and repeatability, expressed as relative
      standard deviation, was from 2 to 6%. The method was used to analyse six red
      wines and the concentrations obtained were statistically compared with those
      obtained by the standard addition method for the same wines.

PMID- 16791576
TI  - Redox-driven transport of copper ions in an emulsion liquid membrane system.
AB  - A new redox-driven type of emulsion liquid membrane separation is described.
      Milligram amounts of copper(II) in 0.2 M hydrochloric acid were reduced to
      copper(I) in the presence of ascorbic acid (1 M identical with 1 mol l(-1)). The
      copper solution was emulsified with a (1+4) mixture of toluene and n-heptane
      using Span-80 (sorbitan monooleate) as an emusifier. The resulting water-in-oil
      emulsion was dispersed in 0.2 M hydrochloric acid containing hydrogen peroxide
      and neocuproine (2,9-dimethyl-1,10-phenanthroline) by stirring for 10 min. The
      copper in the internal aqueous phase was selectively transported to the external
      one, leaving other heavy metals (e.g., Mn, Co, Ni, Cd and Pb) in the internal
      aqueous phase. After collecting the dispersed emulsion globules, they were
      demulsified by heating and the metals in the segregated aqueous phase were
      determined by graphite-furnace atomic absorption spectrometry (GFAAS). The
      selective transport of copper offered the multielement separation of trace heavy
      metals from a copper matrix, allowing the GFAAS determination of impurities at
      the 0.01% level in copper metal.

PMID- 16791577
TI  - Capillary HPLC-ICP MS mapping of selenocompounds in spots obtained from the 2-D
      gel electrophoresis of the water-soluble protein fraction of selenized yeast.
AB  - A method based on ICP collision-cell MS detection in capillary HPLC was developed
      to gain an insight into the purity and identity of selenium-containing proteins
      separated by 1-D and 2-D electrophoresis. The bands and spots obtained after the
      separation of water-soluble proteins in selenized yeast were digested with
      trypsin prior to chromatography. Selenium could be detected down to the
      subpicogram level. The method, assisted by information obtained by MALDI TOF MS
      on the 5000 Da cut-off fraction, permitted the purity of bands and spots to be
      estimated and the efficiency of tryptic digestion and the quantity of selenium
      present in individual peptides to be evaluated. Owing to the high sensitivity and
      the lack of matrix suppression effects, the method provided chromatograms with
      signal-to-noise ratios of 10-1000 in conditions where the common ES Q-TOF MS
      detection failed.

PMID- 16791578
TI  - Cu2+ and Cu+ bathocuproine disulfonate complexes promote the oxidation of the ROS
      detecting compound dichlorofluorescin (DCFH).
AB  - The water-soluble Cu+ chelator bathocuproine disulfonate (BCS) is widely used to
      quantify Cu+ or detect Cu+ formation in Cu2+-initiated oxidation reactions. The
      dichlorofluorescin (DCFH) assay is commonly used to monitor free radical
      reactions, reactive oxygen species (ROS), or reactive nitrogen species (RNS).
      Upon oxidation the non-fluorescent DCFH is converted into the fluorescent
      compound dichlorofluorescein (DCF). In the present communication we show that the
      Cu+ reagent BCS strongly facilitated the oxidation of DCFH in the presence of
      Cu2+ or Cu+. In contrast, 2,2'-dipyridyl (DP), which is also a Cu+-complexing
      reagent, but not as well known and therefore not as commonly used as BCS, did not
      cause any oxidative modification of DCFH in the presence of Cu2+ or Cu+. We
      therefore recommend that DP should be used instead of BCS to complex Cu+ in
      reactions which are initiated by Cu2+ and when ROS/RNS are analyzed by the DCFH
      oxidation assay.

PMID- 16791579
TI  - Vanadium determination in chloride matrices using ICP-MS: finding the optimum
      collision/reaction cell parameters for suppressing polyatomic interferences.
AB  - Efficiencies of He/NH3 and He/H2 collision gases were compared in a conventional
      type of hexapole cell of an inductively coupled plasma mass spectrometer (ICP
      MS). The optimum conditions [hexapole and quadrupole bias voltage (V(H) and V(Q))
      and collision/reaction gas flow rates] were tested for vanadium determination
      (51V) in chloride matrices. When the He/H2 mixture was used, the optimum values
      of V(H) and V(Q) were -10.0 and -8.0 V, respectively. This set-up corresponds to
      the kinetic energy discrimination effect. When the He/NH3 mixture was used, the
      optimum values of V(H) and V(Q) were +10.0 and -7.0 V, respectively. Positive
      V(H) values correspond to the ion kinetic energy effect, which allows the
      reactivity of the ions entering the collision/reaction cell with the reaction gas
      to be controlled. The obtained results showed that the He/H2 mixture is not
      optimal for V determination in samples containing chlorides due to the
      insufficient suppression of the polyatomic interference of 35Cl16O+. Data
      obtained from vanadium determination using the He/NH3 mixture were consistent for
      all selected Cl- concentrations, and the results were acceptable. The detection
      limit was comparable with detection limits obtained from ICP-MS equipped with a
      dynamic reaction cell. Analyses of elements forming interfering molecules, e.g.,
      iron (56Fe), arsenic (75As) and selenium (80Se), were in good agreement with the
      certified values for both studied collision/reaction gas mixtures.

PMID- 16791580
TI  - Stoichiometry determination of (Pb,La)(Zr,Ti)O3-type nano-crystalline
      ferroelectric ceramics by wavelength-dispersive X-ray fluorescence spectrometry.
AB  - Analysis of small samples of lanthanum-doped lead zirconate titanate (PLZT) by
      wavelength-dispersive X-ray fluorescence spectrometry (WDXRF) is presented. The
      powdered material in ca. 30 mg was suspended in water and collected on the
      membrane filter. The pure oxide standards (PbO, La2O3, ZrO2 and TiO2) were used
      for calibration. The matrix effects were corrected using a theoretical influence
      coefficients algorithm for intermediate-thickness specimens. The results from XRF
      method were compared with the results from the inductively coupled plasma optical
      emission spectrometry (ICP-OES). Agreement between XRF and ICP-OES analysis was
      satisfactory and indicates the usefulness of XRF method for stoichiometry
      determination of PLZT.

PMID- 16791581
TI  - Testing equivalence between two laboratories or two methods using paired-sample
      analysis and interval hypothesis testing.
AB  - A modified interval hypothesis testing procedure based on paired-sample analysis
      is described, as well as its application in testing equivalence between two
      bioanalytical laboratories or two methods. This testing procedure has the
      advantage of reducing the risk of wrongly concluding equivalence when in fact two
      laboratories or two methods are not equivalent. The advantage of using paired
      sample analysis is that the test is less confounded by the intersample
      variability than unpaired-sample analysis when incurred biological samples with a
      wide range of concentrations are included in the experiments. Practical aspects
      including experimental design, sample size calculation and power estimation are
      also discussed through examples.

PMID- 16791582
TI  - Effect of tofisopam on the single-oral-dose pharmacokinetics and pharmacodynamics
      of the cyp3a4 probe drug alprazolam.

PMID- 16791583
TI  - Use of omeprazole sulfone in a single plasma sample as a probe for CYP3A4.
AB  - OBJECTIVE: The hydroxylation of omeprazole, measured as the ratio of omeprazole/5
      hydroxyomeprazole in a plasma sample taken 3 h after an oral dose, is an
      established method to determine CYP2C19 activity, and the ratio of omeprazole
      AUC/omeprazole sulfone AUC has been used for assessing CYP3A4 activity. The aim
      of this study was to determine whether the latter ratio from a single 3-h sample
      can also be used for CYP3A4 phenotyping. METHODS: Plasma levels of omeprazole and
      omeprazole sulfone were analyzed by reversed-phase high-performance liquid
      chromatography in a blood sample drawn 3 h after intake of a single oral 20-mg
      dose of omeprazole by 22 healthy subjects and five patients with newly diagnosed
      epilepsy. The procedure was repeated on the 4th day of 200 mg of ketoconazole
      intake (10 subjects), after 3 weeks of 150-200 mg twice-daily carbamazepine (five
      patients), and on the 6th day of 4 mg twice-daily tolterodine (12 subjects). Five
      subjects also took 100 mg and 50 mg of ketoconazole for 3 days before concomitant
      intake with omeprazole. RESULTS: The mean log10(omeprazole/omeprazole sulfone)
      ratio was 0.18 3 h after intake of omeprazole alone. After concomitant intake of
      ketoconazole, the corresponding value was 1.38 (p<0.001); after intake of
      carbamazepine it was -0.42 (p<0.05); and after tolterodine it was 0.29 (not
      significant). In the five subjects taking increasing doses of ketoconazole, the
      ratio was 0.11, 0.79, 1.2, and 1.5 after 0, 50, 100, and 200 mg of ketoconazole,
      respectively. The correlation between the metabolic ratios from the AUC((0-6h))
      and from the single 3-h samples was very good, with a correlation coefficient of
      0.92 (p<0.001). CONCLUSIONS: A single blood sample taken 3 h after intake of 20
      mg of omeprazole can be reliably used to phenotype for both CYP2C19 and CYP3A4
      activity.

PMID- 16791584
TI  - Patterns and utilization of isotretinoin for acne from 1984 to 2003: is there
      need for concern?
AB  - OBJECTIVES: To (1) describe the patterns and trends of isotretinoin utilization
      between 1984 and 2003, (2) describe the characteristics of isotretinoin users
      within that same time period, (3) identify and quantify predictors of
      isotretinoin use, and (4) describe the impact of guidelines on isotretinoin
      utilization between 1984 and 2003. METHODS: Using the Regie de l'Assurance
      Maladie du Quebec (healthcare utilization, medications) and Med-Echo
      (hospitalizations) administrative databases, we conducted a descriptive study on
      a population-based sample of first-time isotretinoin users from 1984 to 2003. We
      determined the characteristics of these users, predictors of an isotretinoin
      treatment >or=20 weeks, and impact of guidelines on the number of new
      isotretinoin users. Guidelines included the implementation of the Pregnancy
      Prevention Program (PPP - 1988) and the Dear Healthcare Professional Letter
      regarding possible psychiatric risks issued to Canadian physicians (DHPL - 2001).
      RESULTS: Mean (SD) age was 23.9 (7.6) years; 50% males, 52% welfare recipients,
      77% urban dwellers, and 55% of prescriptions were written by dermatologists.
      Sixty-four percent of patients did not receive any anti-acne medications in the
      12 months prior to receiving isotretinoin. Thirty-five percent of patients had an
      isotretinoin treatment >or=20 weeks suggested by product guidelines. The odds
      ratio of having a treatment >or=20 weeks significantly increased after the
      implementation of the PPP and other guidelines. There was no statistically
      significant decrease in the number of new isotretinoin users following the
      implementation of the PPP and DHPL. CONCLUSION: These data suggest inappropriate
      isotretinoin utilization, even more so after guidelines were promulgated.

PMID- 16791585
TI  - Use of an online surveillance system for screening drug interactions in
      prescriptions in community pharmacies.
AB  - OBJECTIVE: Computerised surveillance systems have become available for screening
      potential adverse drug interactions during drug prescribing and dispensing. The
      purpose of this study was to analyse the frequency and profile of alerts given by
      one such system in two community pharmacies in Finland. METHODS: In a prospective
      study, all interaction alerts given by the surveillance system were collated
      during September-November 2004 in two community pharmacies in Southern Finland.
      The alerts were categorised into four classes (A-D) according to their clinical
      significance. RESULTS: During the 3-month study period, a total of 39,539
      prescriptions were dispensed. The system flagged 3,861 prescriptions as having
      potential interactions (9.8% of all prescriptions). Since one prescription could
      be the source of several interaction alerts, a total of 5,647 alerts were given.
      The clinically most significant interactions (class D) represented 0.4% of
      prescriptions (3.0% of all interactions). Class C alerts were most prevalent
      (9.4% of all prescriptions, 65.9% of all interactions). The most commonly
      encountered interaction in class D was between warfarin and non-steroidal anti
      inflammatory drugs. CONCLUSIONS: Although the incidence of potentially most
      hazardous interactions in prescriptions is rather low in this study (0.4%), the
      overall incidence is relatively high (9.8%). Implementation of the interaction
      surveillance system in the participating pharmacies makes it possible to study in
      the future in quantitative terms whether the quality of drug dispensing is
      improved.

PMID- 16791587
TI  - The influence of body size on the diving behaviour and physiology of the
      bimodally respiring turtle, Elseya albagula.
AB  - In aquatic vertebrates that acquire oxygen aerially dive duration scales
      positively with body mass, i.e. larger animals can dive for longer periods,
      however in bimodally respiring animals the relationship between dive duration and
      body mass is unclear. In this study we investigated the relationships between
      body size, aquatic respiration, and dive duration in the bimodally respiring
      turtle, Elseya albagula. Under normoxic conditions, dive duration was found to be
      independent of body mass. The dive durations of smaller turtles were equivalent
      to that of larger individuals despite their relatively smaller oxygen stores and
      higher mass specific metabolic rates. Smaller turtles were able to increase their
      dive duration through the use of aquatic respiration. Smaller turtles had a
      relatively higher cloacal bursae surface area than larger turtles, which allowed
      them to extract a relatively larger amount of oxygen from the water. By removing
      the ability to respire aquatically (hypoxic conditions), the dive duration of the
      smaller turtles significantly decreased restoring the normal positive
      relationship between body size and dive duration that is seen in other air
      breathing vertebrates.

PMID- 16791588
TI  - MR urography in children.
AB  - MR urography represents the next step in the evolution of uroradiology in
      children by combining superb anatomic imaging with quantitative functional
      evaluation in a single examination that does not use ionizing radiation. MR
      imaging has inherently greater soft-tissue contrast than other imaging
      techniques. When used in conjunction with dynamic scanning after administration
      of a contrast agent, it provides non-invasive analysis of the perfusion,
      concentration and excretion of each kidney. The purpose of this review is to
      outline our experience with more than 500 MR urograms in children. We outline our
      technique in detail, showing how we calculate differential renal function and how
      we assess concentration and excretion in the different regions of the kidney. We
      show that the dynamic contrast-enhanced data can be processed to yield
      quantitative measures of individual kidney GFR. In the clinical section we show
      how MR urography adds unique aspects to the anatomic evaluation of the urinary
      tract, and by combining the anatomic information with functional information, how
      we assess hydronephrosis and obstructive uropathy, congenital malformations,
      pyelonephritis and renal scarring.

PMID- 16791590
TI  - A novel regulation on developmental gene expression of fruiting body formation in
      Myxobacteria.
AB  - Myxobacteria are Gram-negative soil microorganisms that prey on other
      microorganisms. Myxobacteria have significant potential for applications in
      biotechnology because of their extraordinary ability to produce natural products
      such as secondary metabolites. Myxobacteria also stand out as model organisms for
      the study of cell-cell interactions and multicellular development during their
      complex life cycle. Cellular morphogenesis during multicellular development in
      myxobacteria is very similar to that in the eukaryotic soil amoebae. Recent
      studies have started uncovering molecular mechanisms directing the myxobacterial
      life cycle. We describe recent studies on signal transduction and gene expression
      during multicellular development in the myxobacterium Myxococcus xanthus. We
      provide our current model for signal transduction pathways mediated by a two
      component His-Asp phosphorelay system and a Ser/Thr kinase cascade.

PMID- 16791589
TI  - Overview of bacterial expression systems for heterologous protein production:
      from molecular and biochemical fundamentals to commercial systems.
AB  - During the proteomics period, the growth in the use of recombinant proteins has
      increased greatly in the recent years. Bacterial systems remain most attractive
      due to low cost, high productivity, and rapid use. However, the rational choice
      of the adequate promoter system and host for a specific protein of interest
      remains difficult. This review gives an overview of the most commonly used
      systems: As hosts, Bacillus brevis, Bacillus megaterium, Bacillus subtilis,
      Caulobacter crescentus, other strains, and, most importantly, Escherichia coli
      BL21 and E. coli K12 and their derivatives are presented. On the promoter side,
      the main features of the l-arabinose inducible araBAD promoter (PBAD), the lac
      promoter, the l-rhamnose inducible rhaP BAD promoter, the T7 RNA polymerase
      promoter, the trc and tac promoter, the lambda phage promoter p L , and the
      anhydrotetracycline-inducible tetA promoter/operator are summarized.

PMID- 16791591
TI  - Soluble microbial products (SMP) and soluble extracellular polymeric substances
      (EPS) from wastewater sludge.
AB  - Laspidou and Rittmann (Water Research 36:2711-2720, 2002) proposed that the
      soluble extracellular polymeric substances (EPS) are identical to soluble
      microbial products (SMP) in sludge liquor. In this paper, we compared the
      physicochemical characteristics of the SMP and soluble EPS from original and
      aerobically or anaerobically digested wastewater sludge. The surface charges,
      particle sizes, residual turbidities of polyaluminum chloride (PACl) coagulated
      supernatant, and chemical compositions of the SMP and soluble EPS containing
      suspensions were used as comparison index. Experimental results revealed that the
      particles in SMP and soluble EPS fractions extracted from original wastewater
      sludge, before and after digestion, were not identical in all physicochemical
      characteristics herein measured. The current test cannot support the proposal by
      Laspidou and Rittmann (Water Research 36:2711-2720, 2002) that SMP is identical
      to the soluble EPS from a wastewater sludge.

PMID- 16791592
TI  - Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell
      carcinomas and the surrounding normal mucosa.
AB  - PURPOSE: Several genetic alterations have been reported to contribute to the
      development of oral squamous cell carcinoma (OSCC). Recent studies have shown
      roles of promoter hypermethylation of tumor suppressor genes, including p16 and
      MGMT, in several types of cancers. The purpose of this study is to examine the
      hypermethylation status of p16 and MGMT genes in both oral cancers and normal
      mucosa, surrounding the cancers. METHODS: Promoter hypermethylation status of p16
      and MGMT genes were examined by the methylation-specific PCR (MSP) in OSCC (n =
      51), verrucous carcinoma (n = 2), and carcinoma in situ (n = 2) tissues.
      Moreover, normal mucosa surrounding the cancers were also examined in 22 cases
      out of the 51 OSCCs. As a normal control, oral mucosa from healthy volunteers (n
      = 18) was used. RESULTS: Aberrant promoter hypermethylation of p16 and MGMT genes
      was detected in 50.9% (28 of 55) and 56.4% (31 of 55) of the total malignant
      cases, respectively. As for the 22 OSCC cases, in which paired cancerous tissues
      and the surrounding normal mucosa were examined simultaneously, promoter
      hypermethylation of p16 and MGMT genes was confirmed in 72.73% (16 of 22) and
      68.18% (15 of 22), respectively. In contrast, as for the surrounding normal
      mucosa, promoter hypermethylation of p16 and MGMT genes was recognized in 27.27%
      (6 of 22) cases and 40.91% (9 of 22), respectively. CONCLUSIONS: Hypermethylation
      of both p16 and MGMT genes was frequently detected in not only OSCC tissues, but
      also the surrounding normal mucosa around the cancerous tissues. Thus promoter
      hypermethylation of p16 and MGMT genes are an important, probably early event in
      oral carcinogenesis.

PMID- 16791593
TI  - Combined profile of the tandem repeats CAG, TA and CA of the androgen and
      estrogen receptor genes in breast cancer.
AB  - PURPOSE: Case-control studies have reported inconsistent results concerning the
      association between polymorphisms in the androgen and estrogen receptor (ER)
      genes and breast cancer. While several studies investigated the association
      between the androgen receptor (AR) gene, CAG repeat and breast cancer, for the CA
      and TA repeats in the ER genes there are considerably fewer studies (one for CA
      and none for TA). METHODS: We have investigated the potential link between three
      tandem repeats (CAG, TA, and CA) in the AR, ERs alpha and beta genes,
      respectively, and breast cancer. DNA was isolated from 153 invasive breast tumors
      and 318 controls, and the three tandem repeats were sized by polyacrylamide
      electrophoresis. Number of repeats in each allele and the total repeats of both
      alleles were taken as variables for classification into dichotomous groups using
      the median of each variable in the control group as cut-off point. Relationship
      between polymorphic tandem repeats and breast cancer was assessed by multivariate
      logistic regression models. RESULTS: Three variables combined, longer CAGsum (>
      or =28), shorter TA (<23) and CA (<23) repeats could constitute a possible
      genetic profile associated with breast cancer. CONCLUSIONS: Our results confirm
      previous reports regarding an association between longer CAG repeats and breast
      cancer. In addition to that, we found that the combination of long CAG, short TA
      and CA repeats are strongly associated with breast cancer.

PMID- 16791594
TI  - Tumor-marker analysis and verification of prognostic models in patients with
      cancer of unknown primary, receiving platinum-based combination chemotherapy.
AB  - OBJECTIVES: To evaluate the usefulness of tumor-marker measurements and to
      identify prognostic factors in patients with cancer of unknown primary (CUP),
      receiving platinum-based combination chemotherapy and to verify the adjustment of
      previously reported prognostic models in this population. METHODS: We conducted
      univariate and multivariate analyses in consecutive patients with CUP receiving
      platinum-based combination chemotherapy. Previously reported prognostic models
      were then validated in this population. RESULTS: A total of 93 patients were
      analyzed and the response rate to platinum-based chemotherapeutic regimens among
      the 93 patients was 39.8%. The median time to progression and overall survival
      period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly
      higher in patients with histologically confirmed adenocarcinoma than in patients
      with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A
      multivariate analysis indicated that performance status, the number of involved
      organs, and the serum lactate dehydrogenase level were the prognostic factors of
      the outcome. Both the previously reported prognostic models for predicting the
      duration of survival in this population were shown to be valid. CONCLUSION: Tumor
      marker measurements are not helpful in the management of patients with CUP.
      Previously reported prognostic models may be useful for selecting indication for
      chemotherapy or for stratifying the patients in clinical trial.

PMID- 16791595
TI  - Visual spatial clues enhance ocular torsion response during visual tilt.
AB  - Ocular torsion in response to a static tilt of a visual stimulus has been, and
      still remains in doubt. Furthermore, the possible underlying mechanism is not
      well understood. The authors' hypothesize that if the torsional response is
      related to the vestibular otolith system, then a visual stimulus with spatial
      clues important for maintaining body posture will induce a larger torsional
      response as compared to a stimulus lacking spatial information. Eye movements
      were recorded objectively in 15 healthy individuals using a 3D video oculography
      system. Three visual stimuli were used. In two tests, an identical photographic
      image of a city scene with spatial clues relevant for body posture were used,
      with the only difference being a square periphery in one stimulus (test 1) and a
      circular periphery in the other (test 2). The third stimulus (test 3) consisted
      of yellow rectangles on a black background with no natural spatial information.
      The scenes were tilted in 15 degrees steps from 0 degrees to 45 degrees in CCW
      and CW direction, and each position were held static for 15 s. All visual scene
      tilts induced a compensatory torsional response, which increased with stimuli
      angle. The stimuli with spatial clues induced more torsion compared to the
      stimulus without spatial clues. No difference was found when analysing the
      peripheral contour effect or direction of stimulus tilt. The present results
      support the hypothesis of an origin in the otolith system for the torsional
      response found to a static tilted visual scene.

PMID- 16791596
TI  - Intracoronary beta-brachytherapy using a rhenium-188 filled balloon catheter in
      restenotic lesions of native coronary arteries and venous bypass grafts.
AB  - PURPOSE: We have previously demonstrated the efficacy of intracoronary beta
      brachytherapy using a liquid (188)Re-filled balloon in a randomised trial
      including de novo lesions. Percutaneous coronary interventions in restenotic
      lesions and in stenoses of venous bypass grafts are characterised by a high
      recurrence rate for restenosis and re-interventions. Against this background, we
      wanted to assess the impact of intracoronary beta-brachytherapy using a liquid
      (188)Re-filled balloon in restenotic lesions in native coronary arteries and
      venous bypass grafts. METHODS: In 243 patients, beta-brachytherapy with 22.5 Gy
      was applied at a tissue depth of 0.5 mm. Patients were followed up
      angiographically after 6 months and clinically for 12 months. The primary
      clinical endpoint was the incidence of MACE (death, myocardial infarction, target
      vessel revascularisation). Secondary angiographic endpoints were late loss and
      binary restenosis rate in the total segment. RESULTS: All irradiation procedures
      were successfully performed. A total of 222 lesions were in native coronary
      arteries; 21 were bypass lesions. Mean irradiation length was 41.6+/-17.3 mm
      (range 20-150 mm) in native coronary arteries and 48.1+/-33.9 mm (range 30-180
      mm) in bypass lesions; the reference diameter was 2.57+/-0.52 mm and 2.83+/-0.76
      mm, respectively. There was no vessel thrombosis during antiplatelet therapy.
      Angiographic/clinical follow-up rate was 84%/100%. MACE rate was 17.6% in the
      native coronary artery group and 38.1% in the CABG group (p<0.03). Binary
      restenosis rate was 22.5% and 55.6% (p<0.01), and late loss was 0.38+/-0.72 mm
      and 1.33+/-1.11 mm (p<0.001), respectively. CONCLUSIONS: We conclude that
      intracoronary beta-brachytherapy with a liquid (188)Re-filled balloon using 22.5
      Gy at a tissue depth of 0.5 mm in restenotic lesions is safe. It is associated
      with a low binary restenosis rate, resulting in a low occurrence rate of MACE
      within 12 months in restenotic lesions in native coronary arteries but not in
      vein grafts.

PMID- 16791597
TI  - FDG-PET and CT patterns of bone metastases and their relationship to previously
      administered anti-cancer therapy.
AB  - PURPOSE: To assess (18)F-fluorodeoxyglucose (FDG) uptake in bone metastases in
      patients with and without previous treatment, and compare positive positron
      emission tomography (PET) with osteolytic or osteoblastic changes on computed
      tomography (CT). METHODS: One hundred and thirty-one FDG-PET/CT studies were
      reviewed for bone metastases. A total of 294 lesions were found in 76 patients,
      81 in untreated patients and 213 in previously treated patients. PET was assessed
      for abnormal FDG uptake localised by PET/CT to the skeleton. CT was evaluated for
      bone metastases and for blastic or lytic pattern. The relationship between the
      presence and pattern of bone metastases on PET and CT, and prior treatment was
      statistically analysed using the chi-square test. RESULTS: PET identified 174
      (59%) metastases, while CT detected 280 (95%). FDG-avid metastases included 74/81
      (91%) untreated and 100/213 (47%) treated lesions (p<0.001). On CT there were
      76/81 (94%) untreated and 204/213 (96%) treated metastases (p NS). In untreated
      patients, 85% of lesions were seen on both PET and CT (26 blastic, 43 lytic). In
      treated patients, 53% of lesions were seen only on CT (95 blastic, 18 lytic). Of
      the osteoblastic metastases, 65/174 (37%) were PET positive and 98/120 (82%), PET
      negative (p<0.001). CONCLUSION: The results of the present study indicate that
      when imaging bone metastases, prior treatment can alter the relationship between
      PET and CT findings. Most untreated bone metastases are PET positive and lytic on
      CT, while in previously treated patients most lesions are PET negative and
      blastic on CT. PET and CT therefore appear to be complementary in the assessment
      of bone metastases.

PMID- 16791599
TI  - Interaction of alpha-synuclein and dopamine metabolites in the pathogenesis of
      Parkinson's disease: a case for the selective vulnerability of the substantia
      nigra.
AB  - Parkinson's disease (PD) is the most common movement disorder. Major disease
      symptoms are due to the loss of dopaminergic (DA) neurons in substantia nigra
      (SN). The pathologic hallmark of PD is Lewy bodies (LBs) in the SN and the major
      protein in LBs is alpha-synuclein (AS). A plethora of evidence points towards the
      culpability of AS in the pathogenesis of PD including: (1) linkage of AS
      mutations to familial forms of PD, (2) triplication of the AS locus causing PD,
      and (3) overexpression of AS in transgenic mice and Drosophila leads to PD-like
      phenotypes. Studies of purified AS have revealed its ability to interact with
      diverse molecules including monoamines. Monoamine metabolism is associated with
      oxidative stress conditions that may contribute to DA-AS interactions promoting
      aggregation and neuronal damage. However, in order to explain the selective
      vulnerability of DA neurons there needs to be a link between DA metabolism and AS
      aggregation. Since only the DA neurons contain significant amounts of DA, this
      has been hypothesized to account for the selective vulnerability of SN neurons.
      However, DA itself may not be toxic at physiologic relevant doses, so it is
      probable that other DA metabolites may play a major role in AS aggregation. In
      this review, we discuss the role of the DA metabolite 3,4
      dihydroxyphenylacetaldehyde to provide a plausible link between DA production and
      metabolism, AS aggregation and the pathogenesis of PD.

PMID- 16791598
TI  - Alphavbeta3-integrin imaging: a new approach to characterise angiogenesis?
AB  - OVERVIEW: The field of angiogenesis research is one of the most rapidly growing
      biomedical disciplines. Great efforts are being made to develop anti-angiogenesis
      drugs for treatment of cancer as well as non-oncological diseases. Thus, imaging
      techniques allowing non-invasive monitoring of corresponding molecular processes
      will be of great interest. One target structure involved in the angiogenic
      process is the integrin alphavbeta3, which mediates the migration of activated
      endothelial cells during vessel formation. MATERIALS AND METHODS: A variety of
      radiolabelled RGD peptides have been introduced for monitoring of alphavbeta3
      expression using nuclear medicine tracer techniques. OBJECTIVES: This review
      discusses tracer development and highlights some strategies for tracer
      optimisation. It summarises the preclinical and clinical data and discusses the
      potential of this class of tracer to characterise angiogenesis.

PMID- 16791600
TI  - A missense mutation in the WD40 domain of murine Lyst is linked to severe
      progressive Purkinje cell degeneration.
AB  - Disturbance of intracellular trafficking plays a major role in several
      neurodegenerative disorders including Alzheimer or Parkinson's disease. The
      Chediak-Higashi syndrome (CHS), a life-threatening autosomal recessive disease
      with frequent mutations in the LYST gene, and its animal model, the beige mouse,
      are both characterized by lysosomal defects with accumulation of giant lysosomes.
      Clinically they manifest as hypopigmentation, abnormal bleeding and increased
      susceptibility to infection with various degrees of involvement of the nervous
      system. In the course of a recessive N-ethyl-N-nitrosurea (ENU) mutagenesis
      screen, we identified the first murine missense mutation in the lysosomal
      trafficking regulator gene (Lyst(Ing3618)) located at a highly conserved position
      in the WD40 protein domain. Nearly all described human Lyst alleles lead to
      protein truncation and fatal childhood CHS. Only four different missense
      mutations have been reported in patients with adolescent or adult forms of CHS
      involving the nervous system. Interestingly, the Lyst(Ing3618) model presents
      with a predominant neurodegenerative phenotype with progressive degeneration and
      loss of Purkinje cells and lacks severe impairment of the immune system.
      Therefore, the Lyst(Ing3618 )allele could represent a new model for adult CHS
      with neurological impairment. It could also provide an important tool to
      elucidate the role of neuronal lysosomal trafficking in the pathophysiology of
      neurodegeneration.

PMID- 16791601
TI  - The effects of high-intensity exercise on skeletal muscle neutrophil
      myeloperoxidase in untrained and trained rats.
AB  - The primary purpose of this study was to examine the effects of high-intensity
      acute exercise on neutrophil infiltration in different muscle fiber types of
      untrained rats and to compare postexercise neutrophil accumulation in muscles of
      untrained and trained animals. The effect of high-intensity acute exercise on
      blood neutrophil degranulation reaction in trained animals was also elucidated.
      Neutrophil enzyme myeloperoxidase (MPO) was determined as a measure of neutrophil
      migration into muscles and blood neutrophil degranulation. Male albino rats were
      subjected to acute exercise and 5 weeks of training. The used model of intensive
      acute exercise consisted of 5, 15, and 25 intermittent swimming bouts with the
      addition of weight (8% of total body mass) for 1-min each, followed by 1.5-min
      rest intervals. MPO was analyzed in quadriceps muscle (white and red portion) and
      in soleus muscle 24 h after acute exercise. MPO content in resting blood plasma
      and neutrophils was determined 48-h following the completion of a training
      process. In addition, MPO content in the trained rats was measured immediately
      (in blood plasma and neutrophils) after and 24 h (in muscles) following a single
      bout of exercise to exhaustion. The remaining two-third of the trained animals
      were exposed to a single-bout of nonstop swimming with the addition of 6% body
      mass until exhaustion. These animals were sacrificed immediately and 24 h after
      loaded swimming to analyze leukocyte count, MPO content in blood plasma and
      neutrophils and in muscles, respectively. About 24 h after exercise MPO
      concentrations in the red portion of quadriceps muscle and in soleus muscle were
      4-7-fold higher as compared to the white portion of m. quadriceps. There was an
      association between the quantity of repetitive bouts of swimming and MPO content
      in the muscles. The duration of swimming to exhaustion of trained rats was 3.8
      fold longer than untrained sedentary control. At rest, plasma MPO concentration
      was found to be 40% higher in trained rats compared to untrained controls (P <
      0.05). Postexercise plasma MPO concentrations were significantly higher both in
      untrained (+137%; P < 0.05) and trained (+81%; P < 0.05) rats compared to resting
      values. At rest neutrophil MPO concentration was found to be 33% lower in trained
      rats compared to untrained controls (P < 0.05). There were no significant
      differences in muscle MPO concentrations between untrained and trained rats at
      rest. A single-bout of exercise to exhaustion produced a greater increase in MPO
      content in untrained compared to trained rats. The data suggest that postexercise
      neutrophil infiltration is more intensive in red fibers types compared to white
      fiber types. A smaller neutrophil infiltration in muscles of trained animals
      after exhaustive exercise suggests a protective effect of previous training to
      muscle injury.

PMID- 16791603
TI  - Nephrotic syndrome in a child after umbilical-cord-blood transplantation.
AB  - We report a 12-year-old girl who developed nephrotic syndrome 6 months after
      umbilical-cord-blood transplantation (UCBT) for acute lymphoblastic leukemia
      (L2). In addition to nephrotic syndrome, she also showed autoimmune hemolytic
      anemia, thrombocytopenia and gastrointestinal symptoms. Since these symptoms were
      manifested during the course of tapering immunosuppressive agents, a diagnosis of
      chronic graft-versus-host disease (GVHD) was made. Findings from a kidney biopsy
      were compatible with minimal-change disease (MCD), and focal glomerular capillary
      thrombosis and mild tubular damage were also noted. She was treated with
      methylprednisolone pulse therapy followed by oral prednisolone. Proteinuria
      disappeared in 14 days. Gastrointestinal symptoms, anemia and thrombocytopenia
      were also corrected. This is a case report of nephrotic syndrome as a
      manifestation of chronic GVHD developed after stem-cell transplantation. A review
      of the cases reported in the literature is also made.

PMID- 16791602
TI  - Hyper-IgE syndrome and autoimmunity in Mexican children.
AB  - Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by
      recurrent skin abscesses, recurrent pneumonia with pneumatocele formation,
      eczema, eosinophilia, and elevated levels of serum IgE. Patients with the
      autosomal recessive (AR) form of HIES appear to be prone to developing autoimmune
      diseases. We present two cases of HIES with autoimmune complications; one case
      was a product of a consanguineous marriage, the other one was a sporadic case.
      The first patient presented with recurrent episodes of erythema nodosum, warts,
      bronchiolitis obliterans and thrombocytopenia. The second patient developed
      glomerulonephritis resulting in endstage renal failure. She later developed malar
      rash, oral ulcers, cerebral infarcts with vasculitis and positive ANA, anti
      dsDNA, and antiphospholipid antibodies. We discuss the dilemma in treating
      patients who present with both primary immunodeficiency and autoimmunity.

PMID- 16791604
TI  - Study on hepatitis B virus pre-S/S gene mutations of renal tissues in children
      with hepatitis B virus-associated membranous nephropathy.
AB  - This study aims to clarify the prevalence and significance of the emergence of
      hepatitis B virus (HBV) pre-S/S mutations in children with hepatitis B virus
      associated membranous nephropathy (HBVMN). Direct sequencing of polymerase chain
      reaction products of renal tissue samples that were obtained via percutaneous
      renal biopsy from seven children revealed the presence of HBV DNA. Seven adr
      subtypes were analyzed. Deletions in the HBV pre-S region were observed once per
      seven patients. The deletions were noted in both the pre-S1 (27 bp) and pre-S2
      (60 bp) regions. Various point mutations in the HBV pre-S region were detected in
      all seven patients and proved to be more frequent in the pre-S1 region than in
      the S2 region. Point mutations in the HBV S region were detected in six patients.
      Among these mutations, the mutation in the "a" determinant region was noted in
      five patients. No deletion, however, was observed in the HBV S region. These
      observations suggested that deletions and point mutations in the HBV pre-S1 and
      pre-S2 regions and point mutations in the HBV S region, especially the "a"
      determinant region, are common frequent findings. These results also suggested
      that HBV pre-S/S region mutations may be involved in the pathogenesis in children
      with HBVMN.

PMID- 16791607
TI  - Henoch-Schonlein purpura: polymorphisms in thrombophilia genes.
AB  - Henoch-Schonlein purpura (HSP) is a small-sized vasculitis affecting mainly
      children. Based on the hypothesis that an inherited predilection to
      hypercoagulability may predispose to HSP or may mark those who develop acute
      clinical manifestations, we evaluated the possible roles of
      methylenetetrahydrofolate reductase (MTHFR) gene C677T, factor V (FV) gene G1691A
      (Leiden), and prothrombin gene G20210A polymorphisms in patients with HSP. Fifty
      two HSP patients (32 boys and 20 girls) from different ethnic groups (22 Jews and
      30 Arabs) and 104 ethnically matched controls were studied for these three
      polymorphisms. The frequencies of these mutations for each group, separately and
      in combinations, are described. The mutation frequencies in the MTHFR,
      prothrombin and FV genes in HSP patients did not differ from those in controls.
      In a small number of individuals (n=5) homozygosity for the 677T thermolabile
      variant of MTHFR was associated with hematuria. To summarise, hypercoagulability
      does not seem to play a role in HSP. Studies in larger cohorts and possibly
      inclusion of additional factors may be needed to ascertain whether homozygoty for
      MTHFR 677T polymorphism can influence disease severity.

PMID- 16791605
TI  - Predictive factors of chronic kidney disease in severe vesicoureteral reflux.
AB  - The aim of this retrospective cohort study was to evaluate independent predictive
      factors of chronic kidney disease (CKD) in children with severe bilateral primary
      vesicoureteral reflux (VUR). Between 1970 and 2004, 184 patients were diagnosed
      with VUR (grades III-V) and were systematically followed up at a single tertiary
      renal unit. CKD was defined as estimated glomerular filtration rate <75 ml/min
      per 1.73 m2 body surface area in two consecutive examinations. Risk of CKD was
      analyzed by the Kaplan-Meier method and Cox's regression model. The probability
      of CKD for patients with bilateral severe reflux was estimated at 15% by 10 years
      after VUR diagnosis. After adjustment, four variables remained independently
      associated with CKD during follow-up: age at diagnosis >24 months [relative risk
      (RR)=4.8, 95% confidence interval (95%CI), 1.8-12.7, P<0.001], VUR grade V
      (RR=3.5, 95%CI, 1.5-7.9, P=0.002), bilateral renal damage (RR=2.86, 95%CI, 1.3
      6.1, P=0.007), and decade of admission after 1990 as a protective factor
      (RR=0.16, 95%CI 0.06-0.43, P<0.001). A delay in the diagnosis of VUR more than 12
      months after urinary tract infection (UTI) was also a predictive factor in an
      alternative model (RR=2.2, 95%CI, 1.1-6.6, P=0.03). Prognosis regarding renal
      function was relatively poor after a long-term follow-up of patients with
      bilateral severe reflux.

PMID- 16791608
TI  - Pediatric live-donor kidney transplantation in Mansoura Urology & Nephrology
      Center: a 28-year perspective.
AB  - Our objective was to evaluate our overall experience in pediatric renal
      transplantation. Between March 1976 and March 2004, 1,600 live-donor kidney
      transplantations were carried out in our center; 216 of the patients were 18
      years old or younger (mean age 12.9 years). There were 136 male patients and 80
      female patients. The commonest causes of end-stage renal disease (ESRD) were
      renal dysplasia (22%), nephrotic syndrome (20%), hereditary nephritis (16%), and
      obstructive uropathy (16%). Of the donors, 94% were one-haplotype matched and the
      rest were identical. Pre-emptive transplantation was performed in 51 (23%)
      patients. Triple-therapy immunosuppression (prednisone + cyclosporine +
      azathioprine) was used in 78.2% of transplants. Rejection-free recipients
      constituted 47.7%. Hypertension (62%) was the commonest complication. A
      substantial proportion of patients (48%) were short, with height standard
      deviation score (SDS) less than -1.88. The overall infection rate was high, and
      the majority (53%) of infections were bacterial. The graft survival at 1 year, 5
      years and 10 years were 93.4%, 73.3% and 48.2%, respectively, while the patients'
      survival at 1, 5 and 10 years were 97.6%, 87.8% and 75.3%, respectively. Despite
      long-term success results of pediatric renal transplantation in a developing
      country, there is a risk of significant morbidity.

PMID- 16791609
TI  - Vesicoureteral reflux increases the risk of renal scars: a study of unilateral
      reflux.
AB  - The aim of this study was to assess the impact of vesicoureteral reflux (VUR) on
      renal scar following acute pyelonephritis by comparing the refluxing renal units
      with nonrefluxing renal units in children with unilateral primary VUR. Forty
      eight children with unilateral primary VUR diagnosed after the first
      pyelonephritis were enrolled. Mean age of patients was 1.0+/-1.6 years (29 boys
      and 19 girls). All patients underwent renal ultrasonography and renal 99 m
      technetium dimercaptosuccinic acid (DMSA) scan within three days following the
      diagnosis of pyelonephritis, and voiding cystourethrography (VCU) was performed
      soon after fever subsided and the infection was controlled. The DMSA scan was
      rechecked six months after the initial study when the first scan showed a renal
      defect. The first DMSA showed renal defects in 34 (70.8%) out of 48 of the
      refluxing renal units and in 13 (27.1%) out of 48 of the nonrefluxing renal units
      (P<0.01, OR: 6.54). At six months after the infection, 23 (47.9%) out of 48
      refluxing renal units and seven (14.6%) out of 48 nonrefluxing renal units had
      renal scars on DMSA scan (P<0.01, OR: 5.39). The prevalence of renal scars did
      not vary significantly according to the grade of VUR. The CRP level on admission
      was significantly higher in patients with acute renal defect and scar. In
      conclusion, VUR increases the risk of post-pyelonephritic renal scars in
      children.

PMID- 16791610
TI  - Tuberous sclerosis complex and renal angiomyolipoma: case report and review of
      the literature.
AB  - A 5-year-old boy with a known diagnosis of tuberous sclerosis complex was found
      to have an enlarging renal mass on routine ultrasound. He was diagnosed with an
      angiomyolipoma (AML) and scheduled for close observation. Follow-up magnetic
      resonance imaging demonstrated the AML to be significantly enlarged and
      hypervascular. Selective arterial embolization of the tumor was performed, which
      resulted in an appropriate decrease in tumor size. Angiomyolipoma is a known and
      well-described complication of the tuberous sclerosis complex that is usually
      found among patients in their adolescent and adult years. The case presented here
      illustrates the need for early and repeated renal imaging of younger pediatric
      patients with tuberous sclerosis. Our experience adds to the literature on young
      pediatric patients requiring embolization for treatment of large renal
      angiomyolipomas.

PMID- 16791611
TI  - Serum zinc and copper levels in children with chronic renal failure.
AB  - We evaluated changes in serum zinc (Zn) and copper (Cu) levels in two groups of
      children with chronic renal failure (CRF)--children with CRF who were on regular
      hemodialysis (Group 1, n=40) and children with CRF who were on conservative
      management (Group 2, n=31)--and in one group of healthy children (Group 3, n=30).
      All of the participants in the study were between 5-18 years old, and the
      composition of the three groups was almost identical with respect to age and sex.
      The length of time the children in Group 1 had been on hemodialysis varied
      between 3 and 52 months (mean: 20.97+/-14.8 months). To evaluate the impact of
      the duration of dialysis on serum levels of Zn, we further sub-divided Group 1
      patients into two subgroups: Subgroup A patients (n=20) had been on hemodialysis
      therapy for less than 18 months (mean: 8.85+/-4.83 months); Subgroup B patients
      (n=20) had been on hemodialysis therapy for longer than 18 months (mean: 33.1+/
      10.86 months). The PIXE (proton-induced X-ray emission) was used for measuring
      the trace elements. RESULTS: The mean serum level of Zn was lower in the Group 1
      (hemodialysis group) children than in the children of Group 2 (on conservative
      management) and group 3 (healthy children) (p<0.001), but the difference was not
      significant between Groups 2 and 3. No significant differences in serum levels of
      Cu were found among the three groups. The serum level of Zn was lower in Subgroup
      B than in Subgroup A (p<0.001). The correlation test showed that there was an
      inverse linear relation between the length of time the child was on the
      hemodialysis regimen and serum Zn levels. CONCLUSION: Chronic hemodialysis may
      lead to abnormalities in the serum levels of some trace elements in children with
      CRF that increase in severity with increasing duration of hemodialysis.
      Deficiencies of these trace elements--zinc in particular--may contribute to
      various conditions and symptoms in children undergoing chronic hemodialysis.

PMID- 16791612
TI  - Topical hydrocortisone and physiotherapy for nonretractile physiologic phimosis
      in infants.
AB  - The effect of hydrocortisone (HC), the steroid of lowest potency, and
      physiotherapy (PT) on non-retractile physiologic phimosis (PP) and the reduction
      of subsequent recurrent UTI was evaluated in male infants with UTI. Seventy-eight
      male infants with febrile UTI and nonretractile PP were prospectively randomized
      into HC (Plancol, n=39) and control (Vaseline, n=39) groups. Topical application
      of HC as a thin film around the preputial margin twice a day for four weeks with
      PT was instructed. The response rate in the HC group was 89.7% (35/39), which was
      significantly higher than the rate (20.5%; 8/39) in the control group (P<0.05).
      In the HC group, the response rate was much higher (96.1%) in the subgroup with
      PT than in the group without PT. Most of the response (88.5%) was observed within
      two weeks. During the following year, the recurrent rate of UTI was 7.1% (2/28)
      in the infants with retractile prepuces, which was significantly less than than
      the rate (29.6%; 8/27) in infants with nonretractile prepuces (P<0.05). In
      conclusion, topical HC and PT for 2-4 weeks proved to be a simple, safe and
      effective treatment for nonretractile PP in infants with UTI, and this procedure
      was beneficial in reducing recurrent UTI.

PMID- 16791613
TI  - Heart rate variability, hemostatic and acute inflammatory blood parameters in
      healthy adults after short-term exposure to welding fume.
AB  - The present study aimed to investigate, whether short-term experimental exposure
      to high levels of welding fumes would be capable of exerting acute effects in
      healthy subjects. Specifically, we assessed cardiovascular function in terms of
      heart rate variability (HRV) as well as the concentrations of inflammatory
      mediators and hemostatic proteins in blood as outcome measures. Twenty subjects
      without a history of airway and cardiovascular diseases were exposed to either
      control air or welding fume for 1 h on 2 separate days under standardized
      conditions. The median concentration of the alveolar particle fraction during
      welding was 3.5 mg/m(3 )(quartiles: 1.4-6.3 mg/m(3); range 1.0-25.3 mg/m(3)).
      Five hours later a panel of clinical assessments was performed, including HRV
      measurement and drawing of blood samples. There were no changes in symptom
      ratings or lung function after welding fume exposure. Exposures did also not
      differ regarding effects on time- and frequency-domain parameters of HRV.
      Similarly, blood leukocyte numbers, cell differentials and the blood levels of
      fibrinogen, C-reactive protein, antithrombin III, factor VIII, von Willebrand
      factor, ristocetin cofactor, sICAM-1, tumor necrosis factor alpha, interleukin 6,
      interleukin 8 and epithelial neutrophil activating peptide 78 were not altered by
      welding fume inhalation. However, there was a significant fall in the level of
      endothelin-1 (P < 0.01). In conclusion, the data did not indicate effects of
      clinical significance of a short-term high-level exposure to welding fumes on HRV
      or a set of blood hemostatic and acute inflammatory parameters in healthy
      subjects. The small but statistically significant effect on endothelin levels
      demonstrated that measurable effects could be elicited even in these individuals.
      Overall, welding fumes are not likely to exert acute cardiovascular effects in
      healthy individuals.

PMID- 16791614
TI  - Regional distribution of mutations of the ATP7B gene in patients with Wilson
      disease: impact on genetic testing.
AB  - Wilson disease is an autosomal recessive inherited disorder of copper metabolism.
      The Wilson disease gene codes for a copper transporting P-type ATPase (ATP7B).
      Molecular genetic analysis reveals at least 300 distinct mutations. While most
      reported mutations occur in single families, a few are more common. The most
      common mutation in patients from Central, Eastern, and Northern Europe is the
      point mutation H1069Q (exon 14). About 50-80% of Wilson disease (WD) patients
      from these countries carry at least one allele with this mutation with an allele
      frequency ranging between 30 and 70%. Other common mutations in Central and
      Eastern Europe are located on exon 8 (2299insC, G710S), exon 15 (3400delC) and
      exon 13 (R969Q). The allele frequency of these mutations is lower than 10%. In
      Mediterranean countries there is a wide range of mutations, the frequency of each
      of them varies considerably from country to country. In Sardinia, a unique
      deletion in the 5' UTR (-441/-427 del) is very frequent. In mainland Spain the
      missense mutation M645R in exon 6 is particularly common. Data from non-European
      countries are scarce. Most data from Asia are from Far Eastern areas (China,
      South Korea and Japan) where the R778L missense mutation in exon 8 is found with
      an allele frequency of 14-49%. In summary, given the constant improvement of
      analytic tools genetic testing will become an integral part for the diagnosis of
      WD. Knowledge of the differences in the worldwide distribution of particular
      mutations will help to design shortcuts for genetic diagnosis of WD.

PMID- 16791615
TI  - Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and
      acrocentric heterochromatin in two families with chromosomal translocations.
AB  - We report clinical findings and molecular cytogenetic analyses for two patients
      with translocations [t(14;17)(p12;p12) and t(15;17)(p12;p13.2)], in which the
      chromosome 17 breakpoints map at a large low-copy repeat (LCR) and a breakage
      prone TRE-2 (USP6) oncogene, respectively. In family 1, a 6-year-old girl and her
      5-year-old brother were diagnosed with mental retardation, short stature,
      dysmorphic features, and Charcot-Marie-Tooth disease type 1A (CMT1A). G-banding
      chromosome analysis showed a der(14)t(14;17)(p12;p12) in both siblings, inherited
      from their father, a carrier of the balanced translocation. Chromosome microarray
      and FISH analyses revealed that the PMP22 gene was duplicated. The chromosome 17
      breakpoint was mapped within an approximately 383 kb LCR17pA that is known to
      also be the site of several breakpoints of different chromosome aberrations
      including the evolutionary translocation t(4;19) in Gorilla gorilla. In family
      two, a patient with developmental delay, subtle dysmorphic features, ventricular
      enlargement with decreased periventricular white matter, mild findings of
      bilateral perisylvian polymicrogyria and a very small anterior commissure, a
      cryptic duplication including the Miller-Dieker syndrome region was identified by
      chromosome microarray analysis. The chromosome 17 breakpoint was mapped by FISH
      at the TRE-2 oncogene. Both partner chromosome breakpoints were mapped on the
      short arm acrocentric heterochromatin within or distal to the rRNA cluster,
      distal to the region commonly rearranged in Robertsonian translocations. We
      propose that TRE-2 together with LCR17pA, located approximately 10 Mb apart, also
      generated the evolutionary gorilla translocation t(4;19). Our results support
      previous observations that the USP6 oncogene, LCRs, and repetitive DNA sequences
      play a significant role in the origin of constitutional chromosome aberrations
      and primate genome evolution.

PMID- 16791616
TI  - An angiotensin converting enzyme haplotype predicts survival in patients with end
      stage renal disease.
AB  - The renin-angiotensin system is implicated in the development of a variety of
      human diseases. Many studies have sought to characterize the clinical
      implications of polymorphisms in the angiotensin converting enzyme (ACE) gene.
      Given the high mortality rate of individuals on chronic hemodialysis (HD), we
      sought to investigate whether genetic diversity in the ACE gene correlates with
      mortality in this population. We assembled a racially diverse cohort of prevalent
      individuals on chronic outpatient HD, and followed it prospectively for a mean of
      2.1 years. Subjects were genotyped for seven single nucleotide polymorphisms
      (SNPs) in the ACE gene. Haplotype probabilities were calculated using an
      expectation-maximization algorithm. Cox proportional hazards regression was used
      to determine associations between haplotype and time to mortality from initiation
      of HD. There was strong linkage disequilibrium (LD) across the ACE gene, with
      three tagging SNPs found to account for all seven-SNP haplotypes that had a
      frequency of greater than 4%. After adjustment for age, race, gender, and
      diabetes status, a three-locus haplotype was associated with a 72% risk reduction
      in mortality (P = 0.004). The majority of this association was captured by the TT
      genotype of A-239T promoter polymorphism. The TGG (non-wild-type) haplotype,
      consisting of three tagging SNPs in the ACE gene, is associated with
      significantly decreased risk of all-cause mortality in HD patients independent of
      age, race, gender, and diabetic status. This "protective" haplotype may encompass
      loci with functional significance in the ACE gene.

PMID- 16791617
TI  - Chromosomal telomere attrition as a mechanism for the increased risk of
      epithelial cancers and senescent phenotypes in type 2 diabetes.
AB  - Telomeres are the repeat DNA sequences at the end of chromosomes necessary for
      successful DNA replication and chromosomal integrity. Telomeres shorten at cell
      division at a rate determined by oxidative DNA damage, and cells are triggered
      into replicative senescence once telomeres shorten to a critical length. Telomere
      related chromosomal maintenance also has a role in carcinogenesis. Type 2
      diabetes is characterised by increased oxidative stress, increased oxidative DNA
      damage, senescent retinal and renal phenotypes, and an increased risk of
      epithelial malignancy. We suggest that increased oxidative DNA damage and
      telomere attrition in type 2 diabetes leads to: (1) carcinogenic telomere
      dependent chromosomal non-reciprocal translocations, genomic instability, and the
      development of epithelial cancers; (2) senescent retinal and renal phenotypes
      (expressed as diabetic retinopathy and nephropathy); and (3) senescent vascular
      endothelial, monocyte-macrophage and vascular smooth muscle cells (expressed as
      endothelial dysfunction and accelerated atherogenesis). An adverse intrauterine
      environment leads to increased feto-placental oxidative stress and feto-placental
      oxidative DNA damage. We also suggest that intrauterine oxidative DNA damage and
      telomere shortening is another point at which increased oxidative stress could
      contribute to a pre-programmed increased risk of senescent phenotypes in adult
      offspring, characterised by type 2 diabetes and epithelial malignancy. These
      suggestions can be used to understand early glucose intolerance in the young
      children of type 1 diabetes pregnancies, poor cancer outcomes in type 2 diabetes,
      beta cell fatigue in type 2 diabetes and the absence of increased epithelial
      cancer risk in type 1 diabetes.

PMID- 16791618
TI  - Relationships of physical activity with metabolic syndrome features and low-grade
      inflammation in adolescents.
AB  - AIMS/HYPOTHESIS: Physical activity has beneficial effects on symptoms of the
      metabolic syndrome and low-grade inflammation in adults. These associations have
      rarely been studied in adolescents. Moreover, it has not been established whether
      they depend on adiposity, fat localisation and adipokines. SUBJECTS, MATERIALS
      AND METHODS: We used cross-sectional data of 640 12-year-old adolescents
      participating in the Intervention Centred on Adolescents' Physical Activity and
      Sedentary Behaviour Study (ICAPS). Weight, height, body fat mass and WHR were
      measured. Metabolic syndrome components, two inflammatory markers (IL-6 and C
      reactive protein), plasma leptin, adiponectin and soluble TNF-alpha receptor 1
      (sTNF-alpha R1) were determined. Insulin resistance was estimated by homeostasis
      model assessment (HOMA) and energy expenditure due to organised leisure-time
      physical activity (PAE) assessed by questionnaire. RESULTS: The metabolic
      syndrome was present in 5.8% of the adolescents. After adjustment for sex, sexual
      maturity and socio-economic status, a beneficial relationship between PAE and all
      metabolic syndrome features was found, but only the associations with HOMA and IL
      6 were independent of body fat mass and WHR. Adjusted means from the lowest to
      the highest tertile of PAE were 1.99, 1.80 and 1.78 for HOMA (p=0.04), and 0.88,
      0.69 and 0.70 pg/ml for IL-6 (p=0.02). PAE was inversely associated with leptin,
      independently of body fat mass and WHR (p<10(-2)), but not with adiponectin or
      sTNF-alpha R1. Further adjustment for adipokines did not change the relationships
      of PAE with HOMA and IL-6. CONCLUSIONS/INTERPRETATION: In adolescents, physical
      activity is inversely related to HOMA and IL-6, independently of adiposity and
      fat localisation. These relationships are not accounted for by adipokines.

PMID- 16791619
TI  - Purinergic signaling and microglia.
AB  - Microglial cells are considered as the pathologic sensors of the brain. In this
      paper, we review mechanisms of purinergic signaling in microglia. As ATP is not
      only considered as a physiological signaling substance but is also elevated in
      pathology, it is not surprising that microglia express a variety of P2X, P2Y and
      adenosin receptors. As a rapid physiological event, ATP triggers a cationic
      conductance, increases the potassium conductance and also elicits a calcium
      response. As a long-term effect, purinergic receptor activation is linked to the
      movement of microglial processes and, in the context of pathology, to chemotaxis.
      The purinoreceptors also modulate the release of substances from microglia, such
      as cytokines, nitric oxide, or superoxide, which are important in the context of
      a pathologic response.

PMID- 16791620
TI  - A natural CCL5/RANTES variant antagonist for CCR1 and CCR3.
AB  - The N-terminal domain of the chemokine CCL5/regulated upon activation normal T
      cell expressed and secreted (RANTES) has been shown to be critical for its
      biological activity on leukocytes. Several N-terminus-modified CCL5/RANTES
      derivatives, such as N-Terminal truncated CCL5/RANTES, Met-RANTES, and amino
      oxypentane (AOP)-RANTES exhibited antagonist or partial agonist functions when
      investigated on the properties of their receptors CCR1, CCR3, and CCR5. Studying
      95 African samples from Cameroon, we found a naturally occurring variant of
      CCL5/RANTES containing a missense mutation located in the first amino acid of the
      secreted form (S24F). S24F binds CCR1, CCR3, and CCR5 and triggers receptor down
      modulation comparable to CCL5/RANTES. Moreover, in CCR5 positive cells, S24F
      elicits cellular calcium mobilization equivalent to that obtained with
      CCL5/RANTES. By contrast, S24F does not provoke any response in CCR1 and CCR3
      positive cells. As CCL5/RANTES is able to attract different subtypes of
      leukocytes into inflamed tissue and intervenes in a wide range of allergic and
      autoimmune diseases, the discovery of this natural N-terminus-modified
      CCL5/RANTES analogue exhibiting differential effects on CCL5/RANTES receptors,
      opens up additional perspectives for therapeutic intervention.

PMID- 16791621
TI  - Detailed characterization of the peptide binding specificity of five common Patr
      class I MHC molecules.
AB  - The chimpanzee (Pan troglodytes) is an important model for studying the immune
      response to several human pathogens, but the study of correlates of immunity has
      been hindered by the fact that little is known about the epitope-binding
      specificity of chimpanzee (Patr) class I MHC. In the present study we have
      characterized the peptide binding specificity of several common Patr class I
      molecules. Using single amino acid substitution analogs and large peptide
      libraries, quantitative peptide binding motifs have been derived for Patr A*0101,
      A*0701, A*0901, B*0101, and B*2401. Each molecule was found to bind peptides
      using position 2 and the C terminus as main anchor contacts. On the other hand,
      each Patr molecule is associated with a unique binding specificity, and the range
      of specificities is similar to that seen amongst HLA alleles. A high degree of
      cross-reactivity was noted between Patr A*0701 and Patr A*0901, suggesting the
      existence of a Patr-specific supertype. Consistent with previous studies
      suggesting that some cross-reactivity may exist between HLA and Patr alleles,
      Patr A*0901 was found to have an appreciable degree of cross-reactivity with
      molecules of the HLA A24-supertype. Finally, utilizing motif scans and peptide
      binding and intracellular cytokine staining assays, 77 hepatitis B virus (HBV)
      derived epitopes were identified in five chimpanzees that were recently
      convalescent from acute HBV infection. Because the Patr alleles studied herein
      were found to be very common in two different chimpanzee populations, the present
      data should facilitate the use of chimpanzees for immunological studies.

PMID- 16791622
TI  - Comparative molecular and three-dimensional analysis of the peptide-MHC II
      binding region in both human and Aotus MHC-DRB molecules confirms their
      usefulness in antimalarial vaccine development.
AB  - A vaccine against malaria is desperately needed, and Aotus monkeys are highly
      susceptible to experimental infection with malarial parasites. A thorough
      analysis of this monkey's immune system molecules was thus undertaken in our
      institute. Cloning and sequencing, followed by three-dimensional analysis, has
      revealed high homology with some HLA-DRB1 molecules in terms of their peptide
      binding region pockets. Molecules such as HLA-DRB1*03, 11, 08, and HLA-DRB1*04
      are so similar to Aotus MHC-DRB molecules that peptides identified as binding to
      these molecules and inducing protective immunity in these monkeys could be used
      in humans without further refinement, while small modifications seem to be needed
      for those binding to HLA-DRB1*07, HLA-DRB1*15, 16, and HLA-DRB1*10-like
      molecules, making this New World monkey an excellent model for tailor-made
      vaccine development, especially against malaria.

PMID- 16791623
TI  - Owl monkey MHC-DRB exon 2 reveals high similarity with several HLA-DRB lineages.
AB  - One hundred and ten novel MHC-DRB gene exon 2 nucleotide sequences were sequenced
      in 96 monkeys from three owl monkey species (67 from Aotus nancymaae, 30 from
      Aotus nigriceps and 13 from Aotus vociferans). Owl monkeys, like humans, have
      high MHC-DRB allele polymorphism, revealing a striking similarity with several
      human allele lineages in the peptide binding region and presenting major
      convergence with DRB lineages from several Catarrhini (humans, apes and Old World
      monkeys) rather than with others New World monkeys (Platyrrhini). The parallelism
      between human and Aotus MHC-DRB reveals additional similarities regarding
      variability pattern, selection pressure and physicochemical constraints in amino
      acid replacements. These observations concerning previous findings of similarity
      between the Aotus immune system molecules and their human counterparts affirm
      this specie's usefulness as an excellent animal model in biomedical research.

PMID- 16791624
TI  - [What changes for rheumatologists in the G-DRG system 2006?].
AB  - Once more, the revision of the German DRG catalogue 2006 provides for more
      accurate reimbursement, particularly for specialised medical services. The newly
      established DRG I97Z (Rheumatologische Komplexbehandlung bei Krankheiten und
      Storungen an Muskel-Skelett-System und Bindegewebe) for the complex and
      multimodal treatment of rheumatic diseases allows an accurate picture of clinical
      practice in specialized rheumatologic departments and hospitals. Using this
      specific DRG-description, it will be possible to reduce the financial pressure
      which results from the redistribution of budgets in the second year of the period
      of convergence. A precondition for the affected hospitals is to deal with budget
      planning and calculation of G-DRGs without calculated cost weights for 2006. In
      addition, this article discusses the relevance of other modifications to the G
      DRG system, additional payments, the conditions for payment, the coding
      standards, and the classification systems for diagnosis and procedures.

PMID- 16791626
TI  - [AUO study in hormone-refractory prostate cancer. Phase III study on treatment of
      hormone-refractory prostate cancer (HRPC) with docetaxel: continuous treatment
      vs. intermittent repetition of treatment after renewed progression--PRINCE].

PMID- 16791627
TI  - [Oral anticholinergics in overactive bladder].
AB  - Behavioural therapy and anticholinergics are the mainstays in the treatment of
      symptoms of overactive bladder in patients with idiopathic and neurogenic
      detrusor overactivity; they are the first-line treatment. Oxybutynin,
      propiverine, tolterodine and trospium chloride as well as the "newcomers"
      solifenacin and darifenacin are comparable in regards to their efficacy. However,
      based on different pharmacokinetics and pharmacodynamics with different
      resorption velocity, different metabolisation and different CNS penetration, the
      profile of adverse events is different, qualitatively and quantitatively.
      Substances that are resorbed slowly or available as slow-release formulations are
      tolerated better. Lipophilic anticholinergics which pass the blood-brain barrier
      may compromise cognitive functions, especially in geriatric patients, who are
      already on cholinesterase inhibitors due to memory disorders. The following
      article gives an overview of the anticholinergics currently prescribed in
      patients with symptoms of overactive bladder with special attention to the
      influence of pharmacokinetics/pharmacodynamics on the adverse events profile
      including possible CNS side effects.

PMID- 16791625
TI  - [Role of gene therapy in trauma and orthopedic surgery].
AB  - Modern molecular and genetic technologies enable the modification of a cellular
      genome through transfer of specific genes. The various procedures alter specific
      cell functions, which allow the transfected cell to produce any encoded transgene
      information. The transfected cell then synthesizes proteins that are normally not
      produced or only in very small amounts. Numerous animal studies have demonstrated
      that gene therapy may support and accelerate the healing and regeneration of
      specific tissues such as skin, tendons, cartilage, and bones. Currently, further
      animal studies are evaluating new vectors with reduced immunogenicity in the
      continuous effort to improve the efficacy and safety of gene transfer. In the
      forthcoming decade we expect gene therapy to have an important influence on the
      treatment of fractures, cartilage lesions, and infection.

PMID- 16791628
TI  - [The overactive bladder during childhood: when and how should it be treated?].
AB  - Enuresis is one of the most frequent urinary symptoms in children. 80% suffer
      from primary enuresis nocturna. 20% have urinary incontinence with additional
      symptoms of frequency, urgency and daytime incontinence, which is also defined in
      children as overactive bladder in absence of urinary tract infections,
      neurological, anatomical or further local pathology (OAB in childhood). The
      underlying pathophysiology is a maturation arrest of the bladder control
      resulting in detrusor hyperactivity. In most of the cases the differentiation
      between enuresis and OAB is easily possible with non-invasive primary diagnostic
      procedures. Invasive diagnostic tools like video urodynamic studies may become
      necessary when first-line therapy fails. The treatment options comprise bladder
      training with timed voiding and drink protocols (urotherapy) as well as
      pharmacologic relaxation of detrusor instability by anticholinergic drugs.

PMID- 16791629
TI  - [Noninvasive and invasive bladder cancer: diagnostics and treatment].
AB  - Therapy of superficial bladder tumors is transurethral resection (TUR), and in
      cases of pT1 or high-grade tumors a re-TUR is indicated. Patients with carcinoma
      in situ receive intravesical chemotherapy or BCG for at least 3 months.
      Persistent carcinoma in situ may be treated by radical cystectomy. With the
      provision of a functionally adequate urinary diversion, cystectomy represents an
      effective treatment for patients with muscle-invasive bladder cancer without
      metastatic spread. Regional lymph node metastases can be found in up to 15% of
      stage T1 disease and are present in 33% of stage T3/4 lesions. Thus,
      lymphadenectomy gains diagnostic and possibly also therapeutic importance. For
      selected patients, who cannot be treated by radical cystectomy, multimodal
      concepts aiming to preserve the bladder are discussed. After or prior to
      cystectomy systemic chemotherapy may become necessary for some patients to
      positively affect the course of the disease in cases of locally advanced or
      metastatic lesions.

PMID- 16791630
TI  - Morel-Lavallee lesion in an adolescent with ultrasound and MRI correlation.
AB  - The Morel-Lavallee lesion is a serous collection in the region of the greater
      trochanter, resulting from a closed degloving injury at the deep fascial
      interface. Imaging demonstrates characteristic appearance in relation to this
      lesion, differentiating it from other mass lesions. We report a case of Morel
      Lavallee lesion in an adolescent, with ultrasound and MRI correlation.

PMID- 16791631
TI  - Comparative genomic analysis links karyotypic evolution with genomic evolution in
      the Indian muntjac (Muntiacus muntjak vaginalis).
AB  - The karyotype of Indian muntjacs (Muntiacus muntjak vaginalis) has been greatly
      shaped by chromosomal fusion, which leads to its lowest diploid number among the
      extant known mammals. We present, here, comparative results based on draft
      sequences of 37 bacterial artificial clones (BAC) clones selected by chromosome
      painting for this special muntjac species. Sequence comparison on these BAC
      clones uncovered sequence syntenic relationships between the muntjac genome and
      those of other mammals. We found that the muntjac genome has peculiar features
      with respect to intron size and evolutionary rates of genes. Inspection of more
      than 80 pairs of orthologous introns from 15 genes reveals a significant
      reduction in intron size in the Indian muntjac compared to that of human, mouse,
      and dog. Evolutionary analysis using 19 genes indicates that the muntjac genes
      have evolved rapidly compared to other mammals. In addition, we identified and
      characterized sequence composition of the first BAC clone containing a
      chromosomal fusion site. Our results shed new light on the genome architecture of
      the Indian muntjac and suggest that chromosomal rearrangements have been
      accompanied by other salient genomic changes.

PMID- 16791632
TI  - Cell invasion by Trypanosoma cruzi amastigotes of distinct infectivities: studies
      on signaling pathways.
AB  - Trypanosoma cruzi metacyclic trypomastigotes of the major phylogenetic lineages
      use specific signaling pathways to invade host cells. Using a panel of drugs, we
      studied if the differences in the ability of extracellular amastigotes (EA) from
      G (T. cruzi I) and CL (T. cruzi II) strains to invade host cells could be
      associated to activation of specific signaling routes. Sonicated extracts from G
      or CL strain EA induced transient raises in HeLa cell intracellular Ca(2+) levels
      in a dose-dependent manner. Treatment of EA with drugs that affect Ca(2+) release
      from inositol-1,4,5-triphosphate-sensitive stores did not significantly affect
      the infectivity of either strain, whereas EA of both strains treated with
      ionomycin plus NH(4)Cl or nigericin that release Ca(2+) from acidocalcisomes had
      their infectivity reduced. Treatment of parasites with adenylate cyclase
      activator forskolin increased the infectivity of both strains towards HeLa cells.
      These data, taken together, suggest that, for host cell invasion, G and CL strain
      EA engage signaling pathways that lead to an increase of cyclic adenosine
      monophosphate and Ca(2+) mobilization from acidocalcisomes. Moreover, treatment
      of EA with genistein reduced by approximately 45% the invasion of HeLa cells by G
      but not by CL strain, implicating a protein tyrosine kinase in the process. In
      line with this, HeLa cell extracts contained a protein tyrosine kinase activity
      that mediated the phosphorylation of 87- and 175-kDa polypeptides of EA from G
      but not from CL strain. Regarding the target cell response, the activation of
      host PI3 kinase appears to be required for invasion by either strain as treatment
      of HeLa cells with wortmannin reduced EA infectivity. These data overall
      reinforce the concept that cell invasion by T. cruzi EA markedly differs from the
      process involving metacyclic trypomastigotes.

PMID- 16791633
TI  - Vertical stratification of the termite assemblage in a neotropical rainforest.
AB  - The importance of termites as decomposers in tropical forests has long been
      recognized. Studies on the richness and diversity of termite species and their
      ecological function have flourished in more recent times, but these have been
      mostly conducted in a thin stratum within a standing man's reach. Our aims were
      to evaluate the specific richness and composition of the termite assemblage in
      the canopy of a tropical rainforest and to determine its originality with respect
      to the sympatric ground-level fauna. We conducted systematic searches for canopy
      termites, together with conventional sampling of the sympatric ground-level
      fauna, in the San Lorenzo forest, Panama. We hypothesized that (1) the canopy
      accommodates two categories of wood-feeding termites (long-distance foragers and
      small-colony "one-piece" species) and possibly soil-feeders in suspended soil
      like habitats; (2) due to the abundance of soil-feeders, the overall diversity of
      the ground fauna is higher than that of the canopy; (3) differences in
      microclimate and resource accessibility favour vertical stratification among wood
      feeders. Sixty-three canopy samples yielded ten species of termites, all wood
      feeders. Five of these were not found at ground level, although a total of 243
      ground samples were collected, representing 29 species. In addition to long
      distance foragers (Microcerotermes and Nasutitermes spp.) and small-colony
      termites (mostly Kalotermitidae), the canopy fauna included Termes hispaniolae, a
      wood-feeding Termitidae from an allegedly soil-feeding genus, living in large
      dead branches. Soil-feeders were absent from the canopy, probably because large
      epiphytes were scarce. As predicted, the ground fauna was much richer than that
      of the canopy, but the species richness of both habitats was similar when only
      wood-feeders were considered. Vertical stratification was strongly marked among
      wood-feeders, as all common species, apart from the arboreal-nesting
      Microcerotermes arboreus, could unequivocally be assigned to either a ground or a
      canopy group. The canopy, therefore, contributes significantly to the total
      species richness of the termite assemblage, and the diversity, abundance and
      ecological importance of canopy termites in tropical rainforests may be higher
      than previously recognized.

PMID- 16791634
TI  - Clinical measurements of proprioception, muscle strength and laxity in relation
      to function in the ACL-injured knee.
AB  - A knee injury with anterior cruciate ligament (ACL) rupture may cause deficits in
      proprioception, increased laxity and decreased muscle strength. Although it may
      be common knowledge that these factors affect knee function, only a few studies
      have been performed where this has been investigated in the clinical situation,
      and the results are not conclusive. The purpose of this study was therefore to
      investigate how and to what extent proprioception, laxity and strength affect
      knee joint function and evaluate if the methods commonly used for estimating
      these factors clinically seem to be relevant. The study encompassed 36 patients
      with ACL deficiency. A single-leg hop test for distance and subjective rating of
      knee function were defined as dependent variables and analyzed separately in
      stepwise linear regression models where proprioception, knee joint laxity,
      hamstrings and quadriceps strength, age and sex were defined as independent
      variables. Higher threshold values (poorer proprioception), increased side-to
      side difference of anterior laxity and poorer strength significantly predicted
      shorter length of the hop test. Higher rating of subjective function corresponded
      to female gender, lesser side-to-side difference of anterior laxity and better
      proprioception.

PMID- 16791635
TI  - Magnetic resonance spectroscopy in patients with locally confined prostate
      cancer: association of prostatic citrate and metabolic atrophy with time on
      hormone deprivation therapy, PSA level, and biopsy Gleason score.
AB  - This study was undertaken to determine respective associations between prostatic
      citrate or metabolic atrophy (no detectable citrate, choline, and creatine) at
      magnetic resonance spectroscopy (MRS) and time on hormone-deprivation therapy,
      serum PSA, and biopsy Gleason score. Clinical data, histopathology reports and
      PSA levels of 36 patients on hormone-deprivation therapy (age, 64+/-9 years, pre
      therapeutic biopsy Gleason sum, median 6, range 3-8, antiandrogens only, n=3,
      LHRH-analogues only, n=4, combined hormone-deprivation therapy, n=29, duration,
      27+/-19 weeks) for locally confined prostate cancer (PCA) were retrospectively
      correlated with findings in the peripheral zone of the prostate at 3D-MRS
      (endorectal coil, PRESS, TR 1,000 ms, TE 130 ms). The results show that citrate
      was usually detected after 13 weeks or less of hormone-deprivation therapy (10/12
      vs. 6/24 patients, chi-square-test, p=0.002). All patients with PSA levels
      exceeding 0.20 ng/ml had detectable metabolites (citrate, n=12, choline without
      citrate, n=6), while 9/18 patients with PSA 0.20 ng/ml or less showed metabolic
      atrophy (Fisher-exact-test, p=0.001). There were no significant associations
      between citrate, metabolic atrophy, pre-therapeutic PSA, and biopsy Gleason sum,
      respectively. It has been concluded that hormone-deprivation therapy for locally
      confined PCA has not reached its full deprivation potential after 13 weeks. MRS
      detects prostate metabolism in patients with PSA exceeding 0.20 ng/ml after
      hormone-deprivation therapy.

PMID- 16791636
TI  - Robotic-assisted transhiatal esophagectomy.
AB  - BACKGROUND: Despite its reduced aggressiveness and excellent results obtained in
      certain diseases, minimally invasive surgery did not manage to significantly
      lower the risks of esophageal resections. Further advances in technology led to
      the creation of robotic systems with their unique maneuverability of the
      instruments and exceptional view on the operative field, thus setting the
      prerequisites for performance in complex surgical procedures and offering new
      possibilities to a disease notorious for its dismal prognosis. MATERIALS AND
      METHODS: The robotic-assisted transhiatal esophagectomy technique was used in a
      patient with squamous cell carcinoma of the lower esophagus that had high medical
      risk for surgical therapy. RESULTS: Esophageal resection and reconstruction were
      possible through a robotic-assisted minimally invasive transhiatal approach.
      There were no intraoperative incidents, blood loss was minimal, and lymph node
      dissection and removal was possible during the procedure. Early ambulation and
      conservative treatment of the mild complications that occurred offered a
      favorable postoperative outcome. CONCLUSION: The robotic-assisted transhiatal
      esophagectomy technique is feasible and safe. Complex procedures become less
      technically demanding with the help of the robotic system and, thus, the
      minimally invasive approach can be offered for the benefit of selected patients.
      Further studies are required to confirm these observations and to establish the
      role of this procedure in the future.

PMID- 16791637
TI  - Coordination between manganese and nitrogen within the ligands in the manganese
      complexes facilitates the reconstitution of the water-oxidizing complex in
      manganese-depleted photosystem II preparations.
AB  - The water-oxidizing complex (WOC) within photosystem II (PSII) can be
      reconstituted with synthetic manganese complexes by a process called
      photoactivation; however, the key factors affecting the efficiency of synthetic
      manganese complexes in reconstitution of electron transport and oxygen evolution
      activity in manganese-depleted PSII remain unclear. In the present study, four
      complexes with different manganese coordination environments were used to
      reconstitute the WOC, and an interesting relationship was found between the
      coordination environment of the manganese atom in the complexes and their
      efficiency in restoring electron transport and oxygen evolution. If Mn(II) is
      coordinated to nitrogen atoms within the ligand, it can restore significant rates
      of electron transport and oxygen evolution; however, if the manganese atom is
      coordinated only to oxygen atoms instead of nitrogen atoms, it has no capability
      to restore electron transport and oxygen evolution. So, our results demonstrate
      that the capability of manganese complexes to reconstitute the WOC is mainly
      determined by the coordination between nitrogen atoms from ligands and the
      manganese atom. It is suggested from our results that the ligation between the
      nitrogen atom and the manganese atom within the manganese complex facilitates the
      photoligation of the manganese atom to histidyl residues on the apo-protein in
      manganese-depleted PSII during photoactivation.

PMID- 16791638
TI  - Reduction of dioxygen by enzymes containing copper.
AB  - The reduction of dioxygen is a key step in many important biological processes
      including respiration and ligand oxidation. Enzymes containing either iron or
      copper or, indeed, both elements are often involved in this process, yet the
      catalytic mechanisms employed are not fully understood at the current time
      despite intensive biochemical, spectroscopic and structural studies. The aim of
      this article is to highlight the current structural knowledge regarding the
      process of dioxygen reduction using examples of copper-containing enzymes.

PMID- 16791639
TI  - The first crystal structure of class III superoxide reductase from Treponema
      pallidum.
AB  - Superoxide reductase (SOR) is a metalloprotein containing a non-heme iron centre,
      responsible for the scavenging of superoxide radicals in the cell. The crystal
      structure of Treponema pallidum (Tp) SOR was determined using soft X-rays and
      synchrotron radiation. Crystals of the oxidized form were obtained using
      poly(ethylene glycol) and MgCl2 and diffracted beyond 1.55 A resolution. The
      overall architecture is very similar to that of other known SORs but TpSOR
      contains an N-terminal domain in which the desulforedoxin-type Fe centre, found
      in other SORs, is absent. This domain conserves the beta-barrel topology with an
      overall arrangement very similar to that of other SOR proteins where the centre
      is present. The absence of the iron ion and its ligands, however, causes a
      decrease in the cohesion of the domain and some disorder is observed,
      particularly in the region where the metal would be harboured. The C-terminal
      domain exhibits the characteristic immunoglobulin-like fold and harbours the
      Fe(His)4(Cys) active site. The five ligands of the iron centre are well conserved
      despite some disorder observed for one of the four molecules in the asymmetric
      unit. The participation of a glutamate as the sixth ligand of some of the iron
      centres in Pyrococcus furiosus SOR was not observed in TpSOR. A possible
      explanation is that either X-ray photoreduction occurred or there was a mixture
      of redox states at the start of data collection. In agreement with earlier
      proposals, details in the TpSOR structure also suggest that Lys49 might be
      involved in attraction of superoxide to the active site.

PMID- 16791640
TI  - A mass spectrometric investigation of the binding of gold antiarthritic agents
      and the metabolite [Au(CN)2]- to human serum albumin.
AB  - Electrospray ionisation (ESI) mass spectrometry was used to examine the reactions
      of the clinically used antiarthritic agent [Au(S2O3)2]3-, and AuPEt3Cl, a
      derivative of another clinically used agent auranofin, with human serum albumin
      (HSA) obtained from a human volunteer. Both compounds reacted readily with HSA to
      form complexes containing one or more covalently attached gold fragments. In the
      case of AuPEt3Cl, binding was accompanied by the loss of the chloride ligand,
      while for [Au(S2O3)2]3- the mass spectral data indicated binding of Au(S2O3)
      groups. Experiments performed using HSA with Cys34 blocked by reaction with
      iodoacetamide were consistent with reaction of both gold compounds with this
      amino acid. Separate blocking experiments using diethylpyrocarbonate and AuPEt3Cl
      also provided evidence for histidine residues acting as lower-affinity binding
      sites for this gold compound. ESI mass spectra of solutions containing
      [Au(S2O3)2]3- or [Au(CN)2]-, and HSA, provided evidence for the formation of
      protein complexes in which intact gold molecules were non-covalently bound. In
      the case of [Au(S2O3)2]3-, these non-covalent complexes proved to be transitory
      in nature. However, for [Au(CN)2]- a non-covalent complex containing a single
      gold molecule bound to HSA was found to be stable, and constituted the main
      adduct formed in solutions containing low-to-medium Au-to-HSA ratios. Evidence
      was also obtained for the formation of a covalent adduct in which a single Au(CN)
      moiety was bonded to Cys34 of the protein. AuPEt3Cl reacted to a much lower
      extent with HSA that had Cys34 modified by formation of a disulfide bond to added
      cysteine, than with unmodified HSA. This suggests that the extent of modification
      of the protein in vivo may have an important influence on the transport and
      bioavailability of gold antiarthritic drugs.

PMID- 16791641
TI  - Theoretical study of the catalytic reaction mechanism of MndD.
AB  - Manganese-dependent homoprotocatechuate 2,3-dioxygenase (MndD) is an enzyme
      taking part in the catabolism of aromatic compounds in the environment. It uses
      molecular oxygen to perform an extradiol cleavage of the ring of the ortho
      dihydroxylated aromatic compound homoprotocatechuate. A theoretical investigation
      of the reaction path for MndD was performed using hybrid density functional
      theory with the B3LYP functional, and a catalytic mechanism has been suggested.
      Models of different size were built from the crystal structure of the enzyme and
      were used in the search for intermediates and transition states. It was found
      that the substrate first binds at the active site as a monoanion. Next the
      dioxygen is bound, forming a hydroperoxo intermediate. The O-O bond, activated in
      this way undergoes homolytic cleavage leading to an oxyl and then to an extra
      epoxide radical with subsequent opening of the aromatic ring. The lactone ring is
      then hydrolyzed by the Mn-bound OH group, and the final product is obtained in
      the last reaction steps. Alternative reaction paths were considered, and their
      calculated barriers were found to be higher than for the suggested mechanism. The
      selectivity between the extra- and intra-cleavage pathways was found to be
      determined by the barriers for the decay of the radical state.

PMID- 16791642
TI  - Redox properties of the Fe3+/Fe2+ couple in Arthromyces ramosus class II
      peroxidase and its cyanide adduct.
AB  - The thermodynamics of the one-electron reduction of the ferric heme in free and
      cyanide-bound Arthromyces ramosus peroxidase (ARP), a class II plant peroxidase,
      were determined through spectro-electrochemical experiments. The data were
      compared with those for class III horseradish peroxidase C (HRP) and its cyanide
      adduct, and were interpreted in terms of ligand binding features, electrostatic
      effects and solvent accessible surface area of the heme group and of
      catalytically relevant residues in the heme distal site. The E(o)' values for
      free and cyanide-bound ARP (-0.183 and -0.390 V, respectively, at 25 degrees C
      and pH 7) are higher than those for HRP and HRP-CN. ARP features an enthalpic
      stabilization of the ferrous state and a remarkably negative reduction entropy,
      which are both unprecedented for heme peroxidases. Once the compensatory
      contributions of solvent reorganization are partitioned from the measured
      reduction enthalpy, the resulting protein-based deltaH(o)'(rc(int)) value for ARP
      turns out to be less positive than that for HRP by +10 kJ mol(-1). The smaller
      stabilization of the oxidized heme in ARP most probably results from the less
      pronounced anionic character of the proximal histidine, and the decreased
      polarity in the heme distal site as compared with HRP, as indicated by the X-ray
      structures. The surprisingly negative deltaS(o)'(rc) value for ARP is the result
      of peculiar reduction-induced solvent reorganization effects.

PMID- 16791643
TI  - Theoretical modelling of tripodal CuN3 and CuN4 cuprous complexes interacting
      with O2, CO or CH3CN.
AB  - Dioxygen binding at copper enzymatic sites is a fundamental aspect of the
      catalytic activity observed in many biological systems such as the
      monooxygenases, especially peptidylglycine alpha-hydroxylating monooxygenase
      (PHM), in which two mononuclear Cu(I) sites are involved. Biomimetic models have
      been developed: dipods, tripods, and, more recently, functionalized calixarenes.
      The modelling of calixarene systems, although not unreachable for theory yet,
      requires, however, a number of preliminary investigations to ensure proper
      calibrations if relevant description of the metal-ligand interaction at the
      hybrid quantum mechanical/molecular mechanics levels of theory is the aim. In
      this paper, we report quantum chemistry investigations on a coherent series of
      representative cuprous tripodal species characterized by (1) monodentate ligands
      [Cu(ImH)3]+ (where ImH is imidazole), [Cu(MeNH2)3]+ and [Cu(MeNH2)4]+ , (2)
      neutral tripodal ligands [CuCH(ImH)3]+, [Cu(tren)]+ [where tren is tris(2
      aminoethyl)amine], and [Cu(trenMe3)]+ [where trenMe3 is tris(2
      methylaminoethyl)amine] and (3) a hydrido-tris(pyrazolyl)borate [CuBH(Pyra)3].
      The structures of these complexes, the coordination mode (eta(2) side-on or
      eta(1) end-on) of O2 to Cu(I) and the charge transfer from the metal to dioxygen
      have been computed. For some systems, the coordination by CH3CN and CO is also
      reported. Beyond results relative to structural properties, an interesting
      feature is that it is possible to build from computational results only a set of
      abacuses linking the nu(16O-16O) vibrational frequency of the coordinated O2
      molecule to the O-O bond length or to the net charge of the O2 moiety. Such
      abacuses may help experimentalists in distinguishing between the four possible
      ways of binding O2 to CuN3 and CuN4 cuprous centres, namely (1) end-on triplet
      states, (2) side-on triplet states, (3) end-on singlet states and (4) side-on
      singlet states. These abacuses are extended to three tripods obtained by the
      substitution of one nitrogen atom by either a phosphorus or a sulphur atom.
      Moreover, it is shown that any factor favouring pyramidalization at copper
      favours charge transfer and thus coordination of the incoming O2 moiety. All
      these allow insight into the coordination mode of O2 and into the charge transfer
      from Cu(I) in site Cu(M) of PHM.

PMID- 16791644
TI  - EPR and redox properties of periplasmic nitrate reductase from Desulfovibrio
      desulfuricans ATCC 27774.
AB  - Nitrate reductases are enzymes that catalyze the conversion of nitrate to
      nitrite. We report here electron paramagnetic resonance (EPR) studies in the
      periplasmic nitrate reductase isolated from the sulfate-reducing bacteria
      Desulfovibrio desulfuricans ATCC 27774. This protein, belonging to the dimethyl
      sulfoxide reductase family of mononuclear Mo-containing enzymes, comprises a
      single 80-kDa subunit and contains a Mo bis(molybdopterin guanosine dinucleotide)
      cofactor and a [4Fe-4S] cluster. EPR-monitored redox titrations, carried out with
      and without nitrate in the potential range from 200 to -500 mV, and EPR studies
      of the enzyme, in both catalytic and inhibited conditions, reveal distinct types
      of Mo(V) EPR-active species, which indicates that the Mo site presents high
      coordination flexibility. These studies show that nitrate modulates the redox
      properties of the Mo active site, but not those of the [4Fe-4S] center. The
      possible structures and the role in catalysis of the distinct Mo(V) species
      detected by EPR are discussed.

PMID- 16791645
TI  - Highly efficient photoactivation of Mn-depleted photosystem II by imidazole
      liganded manganese complexes.
AB  - The oxygen-evolving complex (OEC) of Mn-depleted photosystem II (PSII) can be
      reconstituted in the presence of exogenous Mn or a Mn complex under weak
      illumination, a process called photoactivation. Synthetic Mn complexes could
      provide a powerful system to analyze the assembly of the OEC. In this work, four
      mononuclear Mn complexes, [(terpy)2Mn(II)(OOCH3)] x 2 H2O (where terpy is
      2,2':6',2''-terpyridine), Mn(II)(bzimpy)2, Mn(II)(bp)2(CH3CH2OH)2 [where bzimpy
      is 2,6-bis(2-benzimidazol-2-yl)pyridine] and [Mn(III)(HL)(L)(py)(CH3OH)]CH3OH
      (where py is pyridine) were used in photoactivation experiments. Measurements of
      the photoreduction of 2,6-dichorophenolindophenol and oxygen evolution
      demonstrate that photoactivation is more efficient when Mn complexes are used
      instead of MnCl2 in reconstructed PSII preparations. The most efficient
      recoveries of oxygen evolution and electron transport activities are obtained
      from a complex, [Mn(III)(HL)(L)(py)(CH3OH)]CH3OH, that contains both imidazole
      and phenol groups. Its recovery of the rate of oxygen evolution is as high as 79%
      even in the absence of the 33-kDa peptide. The imidazole ligands of the Mn
      complex probably accelerate P680*+ reduction and consequently facilitate the
      process of photoactivation. Also, the strong intermolecular hydrogen bond
      probably facilitates interaction with the Mn-depleted PSII via reorganization of
      the hydrogen-bonding network, and therefore promotes the recovery of oxygen
      evolution and electron transport activities.

PMID- 16791646
TI  - Structure and membrane affinity of new amphiphilic siderophores produced by
      Ochrobactrum sp. SP18.
AB  - The coastal alpha-proteobacterium Ochrobactrum sp. SP18 produces a suite of three
      citrate-derived, cell-associated amphiphilic siderophores, ochrobactins A-C. The
      ochrobactins are composed of a citric acid backbone amide-linked to two lysine
      residues. Each epsilon-amine of lysine is hydroxylated and acylated forming two
      hydroxamic acid moieties. One of the acylated appendages of each ochrobactin is
      (E)-2-decenoic acid. The other acylated appendages for ochrobactins A-C are (E)-2
      octenoic acid, octanoic acid and (E)-2-decenoic acid, respectively. The ferric
      ochrobactin complexes are photoreactive in UV light, producing an oxidized ligand
      with loss of 46 mass units that can still coordinate Fe(III). The relative
      partitioning of the apo-ochrobactins, Fe(III) ochrobactins and Fe(III)
      photoproducts into 1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles is
      presented. The ochrobactins are the first example of aerobactin-based
      siderophores with two fatty acid appendages produced in a suite with varying acyl
      appendage lengths.

PMID- 16791647
TI  - Pyrococcus furiosus 4Fe-ferredoxin, chemisorbed on gold, exhibits gated reduction
      and ionic strength dependent dimerization.
AB  - Pyrococcus furiosus ferredoxin is a small metalloprotein that shuttles electrons
      between redox enzymes. In its native 4Fe-4S form the protein is highly
      thermostable. In addition to three cluster-ligating cysteines, two surface
      cysteine residues (C21 and C48) are present. We used the reactivity of these
      surface thiols to directly immobilize ferredoxin on a bare gold electrode, with
      an orientation in which the cluster is exposed to solution. Voltammetry, X-ray
      photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) studies
      established the immobilization of the 4Fe form. Native and recombinant wild-type
      ferredoxins were compared with the C48S, C21S, and C21S/C48S mutants. The
      variants with one and two surface cysteines can be directly chemisorbed on bare
      gold. Cyclic voltammetry demonstrated that the reduction potentials are similar
      to those in solution. The interfacial electron transfer kinetics revealed that
      the reduction is gated by the interconversion between two oxidized species. AFM
      images showed that dimers are chemisorbed at low ionic strength, while monomers
      are present at high ionic strength. XPS spectra revealed the presence of S, Fe,
      C, N, and O at the surface, which are assigned to the corresponding atoms in the
      peptide and the cofactor. Analysis of the sulfur spectrum corroborates that both
      C21 and C48 form gold-thiolate bonds. Moreover, two inorganic sulfide and two
      iron species were identified, suggesting an inhomogeneous charge distribution in
      the 4Fe-4S cluster. In conclusion, P. furiosus ferredoxin can be directly and
      vectorially chemisorbed on gold with retention of its properties. This may
      provide a biocompatible electrode surface with docking sites for redox enzymes.

PMID- 16791649
TI  - A theory of Fisher's reproductive value.
AB  - The formal Darwinism project aims to provide a mathematically rigorous basis for
      optimisation thinking in relation to natural selection. This paper deals with the
      situation in which individuals in a population belong to classes, such as sexes,
      or size and/or age classes. Fisher introduced the concept of reproductive value
      into biology to help analyse evolutionary processes of populations divided into
      classes. Here a rigorously defined and very general structure justifies, and
      shows the unity of concept behind, Fisher's uses of reproductive value as
      measuring the significance for evolutionary processes of (i) an individual and
      (ii) a class; (iii) recursively, as calculable for a parent as a sum of its
      shares in the reproductive values of its offspring; and (iv) as an evolutionary
      maximand under natural selection. The maximand is the same for all parental
      classes, and is a weighted sum of offspring numbers, which implies that a
      tradeoff in one aspect of the phenotype can legitimately be studied separately
      from other aspects. The Price equation, measure theory, Markov theory and
      positive operators contribute to the framework, which is then applied to a number
      of examples, including a new and fully rigorous version of Fisher's sex ratio
      argument. Classes may be discrete (e.g. sex), continuous (e.g. weight at
      fledging) or multidimensional with discrete and continuous components (e.g. sex
      and weight at fledging and adult tarsus length).

PMID- 16791650
TI  - Pair-level approximations to the spatio-temporal dynamics of epidemics on
      asymmetric contact networks.
AB  - The process of infection during an epidemic can be envisaged as being transmitted
      via a network of routes represented by a contact network. Most differential
      equation models of epidemics are mean-field models. These contain none of the
      underlying spatial structure of the contact network. By extending the mean-field
      models to pair-level, some of the spatial structure can be contained in the
      model. Some networks of transmission such as river or transportation networks are
      clearly asymmetric, whereas others such as airborne infection can be regarded as
      symmetric. Pair-level models have been developed to describe symmetric contact
      networks. Here we report on work to develop a pair-level model that is also
      applicable to asymmetric contact networks. The procedure for closing the model at
      the level of pairs is discussed in detail. The model is compared against
      stochastic simulations of epidemics on asymmetric contact networks and against
      the predictions of the symmetric model on the same networks.

PMID- 16791651
TI  - Simulating complex tumor dynamics from avascular to vascular growth using a
      general level-set method.
AB  - A comprehensive continuum model of solid tumor evolution and development is
      investigated in detail numerically, both under the assumption of spherical
      symmetry and for arbitrary two-dimensional growth. The level set approach is used
      to obtain solutions for a recently developed multi-cell transport model
      formulated as a moving boundary problem for the evolution of the tumor. The model
      represents both the avascular and the vascular phase of growth, and is able to
      simulate when the transition occurs; progressive formation of a necrotic core and
      a rim structure in the tumor during the avascular phase are also captured. In
      terms of transport processes, the interaction of the tumor with the surrounding
      tissue is realistically incorporated. The two-dimensional simulation results are
      presented for different initial configurations. The computational framework,
      based on a Cartesian mesh/narrow band level-set method, can be applied to similar
      models that require the solution of coupled advection-diffusion equations with a
      moving boundary inside a fixed domain. The solution algorithm is designed so that
      extension to three-dimensional simulations is straightforward.

PMID- 16791652
TI  - Symmetric time warping, Boltzmann pair probabilities and functional genomics.
AB  - Given two time series, possibly of different lengths, time warping is a method to
      construct an optimal alignment obtained by stretching or contracting time
      intervals. Unlike pairwise alignment of amino acid sequences, classical time
      warping, originally introduced for speech recognition, is not symmetric in the
      sense that the time warping distance between two time series is not necessarily
      equal to the time warping distance of the reversal of the time series. Here we
      design a new symmetric version of time warping, and present a formal proof of
      symmetry for our algorithm as well as for one of the variants of Aach and Church
      [1]. We additionally design quadratic time dynamic programming algorithms to
      compute both the forward and backward Boltzmann partition functions for symmetric
      time warping, and hence compute the Boltzmann probability that any two time
      series points are aligned. In the future, with the availability of increasingly
      long and accurate time series gene expression data, our algorithm can provide a
      sense of biological significance for aligned time points - e.g. our algorithm
      could be used to provide evidence that expression values of two genes have higher
      Boltzmann probability (say) in the G1 and S phase than in G2 and M phases.
      Algorithms, source code and web interface, developed by the first author, are
      made publicly available via the Boltzmann Time Warping web server at
      bioinformatics.bc.edu/clotelab/.

PMID- 16791653
TI  - A mesoscopic model for helical bacterial flagella.
AB  - Filaments of bacterial flagella are perfect tubular stackings polymerized out of
      just one kind of building block: the flagellin protein. Surprisingly, they do not
      form straight tubes, but exhibit a symmetry-breaking coiling into helical shapes
      which is essential for their biological function as cell "propeller''. The co
      existence of two conformational states for flagellin within the filament is
      believed to be responsible for the helical shapes by producing local misfit which
      results in curvature and twist. In this paper, we present a coarse-grained
      description with an elastic energy functional for the filament derived from its
      microscopic structure. By minimising this functional we can answer the question
      of spatial distribution of flagellin states which is crucial for the observed
      coupling of curvature and twist. Our approach extends a classical theory of
      Calladine, which had to assume this spatial distribution from the outset.

PMID- 16791654
TI  - The asymptotic behavior of solutions of the buffered bistable system.
AB  - In this paper, we study a model for calcium buffering with bistable nonlinearity.
      We present some results on the stability of equilibrium states and show that
      there exists a threshold phenomenon in our model. In comparing with the model
      without buffers, we see that stationary buffers cannot destroy the asymptotic
      stability of the associated equilibrium states and the threshold phenomenon.
      Moreover, we also investigate the propagation property of solutions with initial
      data being a disturbance of one of the stable states which is confined to a half
      line. We show that the more stable state will eventually dominate the whole
      dynamics and that the speed of this propagation (or invading process) is
      positive.

PMID- 16791655
TI  - End of life in the intensive care unit: from practice to law. What do the
      lawmakers tell the caregivers? A new series in Intensive Care Medicine.

PMID- 16791656
TI  - Fluid resuscitation of hypovolemic shock: acute medicine's great triumph for
      children.

PMID- 16791657
TI  - Recognizing the apical ballooning syndrome in the intensive care unit.

PMID- 16791658
TI  - Elderly patients and intensive care medicine.

PMID- 16791659
TI  - Virus diseases in ICU patients: a long time underestimated; but be aware of
      overestimation.

PMID- 16791660
TI  - Optimal therapy for severe pneumococcal community-acquired pneumonia.
AB  - Streptococcus pneumoniae is responsible for two-thirds of ICU admissions due to
      community-acquired pneumonia (CAP) and is the leading cause of CAP-related death.
      Early death is principally due to cardiovascular collapse, whereas late death is
      associated with hypoxemic respiratory failure. Outcome depends on interactions
      between non-modifiable factors of predisposition (age, comorbidities, host
      defences, genetic predisposition) or infection (toxins, virulence, bacterial
      burden) and modifiable factors (organ-failure support, surgical drainage for
      empyema, adjuvant therapies and antibiotics). Excess mortality has been reported
      when initial therapy is discordant, but more than 95% of isolates have minimum
      inhibitory concentration (MIC) <4 microg/ml. Therefore, cefotaxime, ceftriaxone
      and high doses of amoxicillin remain successful for non-meningeal infections.
      Recent studies suggest that initial combination therapy improves survival in the
      subset of bacteremic episodes with highest severity, conceivably due to the
      immunomodulatory effects of macrolides. Prospective, randomized clinical trials
      of pneumonia patients with a pneumonia severity index score above 90 are
      warranted to define optimal antibiotic regimens.

PMID- 16791662
TI  - Fluid resuscitation in neonatal and pediatric hypovolemic shock: a Dutch
      Pediatric Society evidence-based clinical practice guideline.
AB  - OBJECTIVE: To develop a clinical practice guideline that provides recommendations
      for the fluid, i.e. colloid or crystalloid, used for resuscitation in critically
      ill neonates and children up to the age of 18 years with hypovolemia. METHODS:
      The guideline was developed through a comprehensive search and analysis of the
      pediatric literature. Recommendations were formulated by a national
      multidisciplinary committee involving all stakeholders in neonatal and pediatric
      intensive care and were based on research evidence from the literature and, in
      areas where the evidence was insufficient or lacking, on consensus after
      discussions in the committee. RESULTS: Because of the lack of evidence in
      neonates and children, trials conducted in adults were considered. We found
      several recent meta-analyses that show excess mortality in albumin-treated
      groups, compared with crystalloid-treated groups, and one recent large randomized
      controlled trial that found evidence of no mortality difference. We found no
      evidence that synthetic colloids are superior to crystalloid solutions.
      CONCLUSIONS: Given the state of the evidence and taking all other considerations
      into account, the guideline-developing group and the multidisciplinary committee
      recommend that in neonates and children with hypovolemia the first-choice fluid
      for resuscitation should be isotonic saline.

PMID- 16791661
TI  - Applications of transcranial Doppler in the ICU: a review.
AB  - OBJECTIVE: Transcranial Doppler (TCD) ultrasonography is a technique that uses a
      hand-held Doppler transducer (placed on the surface of the cranial skin) to
      measure the velocity and pulsatility of blood flow within the intracranial and
      the extracranial arteries. This review critically evaluates the evidence for the
      use of TCD in the critical care population. DISCUSSION: TCD has been frequently
      employed for the clinical evaluation of cerebral vasospasm following subarachnoid
      haemorrhage (SAH). To a lesser degree, TCD has also been used to evaluate
      cerebral autoregulatory capacity, monitor cerebral circulation during
      cardiopulmonary bypass and carotid endarterectomies and to diagnose brain death.
      Technological advances such as M mode, colour Doppler and three-dimensional power
      Doppler ultrasonography have extended the scope of TCD to include other non
      critical care applications including assessment of cerebral emboli, functional
      TCD and the management of sickle cell disease. CONCLUSIONS: Despite publications
      suggesting concordance between TCD velocity measurements and cerebral blood flow
      there are few randomized controlled studies demonstrating an improved outcome
      with the use of TCD monitoring in neurocritical care. Newer developments in this
      technology include venous Doppler, functional Doppler and use of ultrasound
      contrast agents.

PMID- 16791663
TI  - Under-humidification and over-humidification during moderate induced hypothermia
      with usual devices.
AB  - OBJECTIVE: In mechanically ventilated patients with induced hypothermia, the
      efficacy of heat and moisture exchangers and heated humidifiers to adequately
      humidify the airway is poorly known. The aim of the study was to assess the
      efficacy of different humidification devices during moderate hypothermia. DESIGN:
      Prospective, cross-over randomized study. SETTINGS: Medical Intensive Care Unit
      in a University Hospital. PATIENTS AND PARTICIPANTS: Nine adult patients
      hospitalized after cardiac arrest in whom moderate hypothermia was induced (33
      degrees C for 24[Symbol: see text]h). INTERVENTIONS: Patients were ventilated at
      admission (period designated "normothermia") with a heat and moisture exchanger,
      and were randomly ventilated during hypothermia with a heat and moisture
      exchanger, a heated humidifier, and an active heat and moisture exchanger.
      MEASUREMENTS AND RESULTS: Core temperature, inspired and expired gas absolute and
      relative humidity were measured. Each system demonstrated limitations in its
      ability to humidify gases in the specific situation of hypothermia. Performances
      of heat and moisture exchangers were closely correlated to core temperature (r
      (2)[Symbol: see text]=[Symbol: see text]0.84). During hypothermia, heat and
      moisture exchangers led to major under-humidification, with absolute humidity
      below 25[Symbol: see text]mgH(2)O/l. The active heat and moisture exchanger
      slightly improved humidification. Heated humidifiers were mostly adequate but led
      to over-humidification in some patients, with inspiratory absolute humidity
      higher than maximal water content at 33 degrees C with a positive balance between
      inspiratory and expiratory water content. CONCLUSIONS: These results suggest that
      in the case of moderate hypothermia, heat and moisture exchangers should be used
      cautiously and that heated humidifiers may lead to over-humidification with the
      currently recommended settings.

PMID- 16791664
TI  - Virus infection in exacerbations of chronic obstructive pulmonary disease
      requiring ventilation.
AB  - OBJECTIVES: We aimed to characterise and quantify the incidence of common
      infectious agents in acute exacerbations of chronic obstructive pulmonary disease
      (COPD) requiring ventilation, with a focus on respiratory viruses. DESIGN: An
      epidemiological study conducted over 3 years. SETTING: A 12-bed intensive care
      unit (ICU). PARTICIPANTS: ICU patients over 45 years of age with a primary
      diagnosis of COPD exacerbation requiring non-invasive ventilation (NIV) or
      ventilation via endotracheal tube (ETT). MATERIALS AND METHODS: Nasopharyngeal
      aspirates (NPA) and posterior pharyngeal swabs (PS) were tested for viruses with
      immunofluorescence assay (IFA), virus culture (VC) and polymerase chain reaction
      (PCR). Paired virus and atypical pneumonia serology assays were taken. Blood,
      sputum and endotracheal aspirates were cultured for bacteria. RESULTS: 107
      episodes in 105 patients were recorded. Twenty-three (21%) died within 28[Symbol:
      see text]days. A probable infectious aetiology was found in 69 patient episodes
      (64%). A virus was identified in 46 cases (43%), being the sole organism in 35
      cases (33%) and part of a mixed infection in 11 cases (10%). A probable bacterial
      aetiology was found in 25 cases (23%). There was no statistically significant
      difference in clinical characteristics or outcomes between the group with virus
      infections and that without. CONCLUSION: Forty-six (43%) of the patients with
      COPD exacerbation requiring mechanical ventilation had a probable viral pathogen.
      Prodromal, clinical and outcome parameters did not distinguish virus from non
      virus illness. PCR was the most sensitive whilst virus culture was the least of
      virus assays.

PMID- 16791665
TI  - Cardiac response is greater for colloid than saline fluid loading after cardiac
      or vascular surgery.
AB  - OBJECTIVE: To study the effects on volume expansion and myocardial function of
      colloids or crystalloids in the treatment of hypovolaemic hypotension after
      cardiac and major vascular surgery. DESIGN AND SETTING: A single-centre, single
      blinded, randomized clinical trial at the intensive care unit of a university
      hospital. PATIENTS AND METHODS: Patients (n=67) were subjected to a 90-min
      filling pressure-guided fluid challenge with saline 0.9% or the colloids gelatin
      4%, hydroxyethyl starch 6% or albumin 5%. Biochemical variables and haemodynamics
      (transpulmonary thermodilution) were measured. RESULTS: An amount of 1800 (1300
      1800) ml of saline or 1600 (750-1800) ml of colloid solution (P< 0.005) was
      infused. Colloid osmotic pressure (COP) decreased in the saline group and
      increased in the colloid groups (P< 0.001). Plasma volume increased by 3.0% (-18
      to 24) in the saline versus 19% (-11 to 50) in the colloid groups (P< 0.001).
      Cardiac index increased by median 13% (ns) in the saline group and by 22% in the
      colloid groups (P<0.005). The rise in left ventricular stroke work index was
      greater in the colloid than in the saline groups. The different colloids were
      equally effective. The rise in cardiac index related to the rise in plasma volume
      and global end-diastolic volume, confirming plasma volume and preload
      augmentation by the fluid loading. CONCLUSION: After cardiac or major vascular
      surgery, the pressure- and time-guided fluid response is dependent on the type of
      fluid used. Colloid fluid loading leads to a greater increase in preload
      recruitable cardiac and left ventricular stroke work indices than that with
      saline, because of greater plasma volume expansion following an increase in
      plasma COP.

PMID- 16791666
TI  - Short-term and long-term mortality in very elderly patients admitted to an
      intensive care unit.
AB  - OBJECTIVE: To report short-term and long-term mortality of very elderly ICU
      patients and to determine independent risk factors for short-term and long-term
      mortality DESIGN AND SETTING: Retrospective cohort study in the medical/surgical
      ICU of a tertiary university teaching hospital. PATIENTS: 578 consecutive ICU
      patients aged 80 years or older. RESULTS: Demographic, physiological, and
      laboratory values derived from the first 24h after ICU admission. ICU mortality
      of unplanned surgical (34.0%) and medical patients (37.7%) was higher than that
      of planned surgical patients (10.6%), as was post-ICU hospital mortality (26.5%
      and 29.7% vs. 4.4%). Mortality 12 months after hospital discharge, including ICU
      and hospital mortality, was 62.1% in unplanned surgical and 69.2% in medical
      patients vs. 21.6% in planned patients. Only median survival of planned surgical
      patients did not differ from survival in the age- and gender-matched general
      population. Independent risk factors for ICU mortality were lower Glasgow Coma
      Scale score, higher SAPS II score, the lowest urine output over 8 h, abnormal
      body temperature, low plasma bicarbonate levels, and higher oxygen fraction of
      inspired air. High urea concentrations and admission type were risk factors for
      hospital mortality, and high creatinine concentration was an independent risk
      factor for 12-month mortality. CONCLUSION: Mortality in very elderly patients
      after unplanned surgical or medical ICU admission is higher than after planned
      admission. The most important factors independently associated with ICU mortality
      were related to the severity of illness at admission. Long-term mortality was
      associated with renal function.

PMID- 16791667
TI  - Decision-making process, outcome, and 1-year quality of life of octogenarians
      referred for intensive care unit admission.
AB  - OBJECTIVE: To describe triage decisions and subsequent outcomes in octogenarians
      referred to an ICU. DESIGN AND SETTING: Prospective observational study in the
      medical ICU in a tertiary nonuniversity hospital. PARTICIPANTS: Cohort of 180
      patients aged 80 years or over who were triaged for admission. MEASUREMENTS: Age,
      underlying diseases, admission diagnoses, Mortality Probability Model score, and
      mortality were recorded. Self-sufficiency (Katz Index of Activities of Daily
      Living) and quality of life (modified Perceived Quality of Life scale and
      Nottingham Health Profile) were measured 1year after triage. RESULTS: In 132
      patients (73.3%) ICU admission was refused, including 79 (43.8%) considered too
      sick to benefit. Factors independently associated with refusal were nonsurgical
      status, age older than 85 years, and full unit. Greater self-sufficiency was
      associated with ICU admission. Hospital mortality was 30/48 (62.5%), 56/79
      (70.8%), 9/51 (17.6%), and 0/2 in the admitted, too sick to benefit, too well to
      benefit, and family/patient refusal groups, respectively; 1-year mortality was
      34/48 (70.8%), 69/79 (87.3%), 24/51 (47%), and 0/2, respectively. Self
      sufficiency was unchanged by ICU stay. Quality of life (known in only 28
      patients) was significantly poorer for isolation, emotional, and mobility domains
      compared to the French general population matched on sex and age. CONCLUSIONS:
      More than two-thirds of patients aged over 80 years referred to our ICU were
      denied admission. One year later self-sufficiency was not modified and quality of
      life was poorer than in the general population. These results indicate a need to
      discuss patient preferences before triage decisions.

PMID- 16791668
TI  - Short- and long-term outcomes of older patients in intermediate care units.
AB  - OBJECTIVE: To evaluate short- and long-term outcomes of elderly patients (>or=65
      years) treated at an intermediate care unit (IMCU) and to identify outcome
      predictors. DESIGN AND SETTING: Prospective observational study in the IMCU of a
      university teaching hospital. PARTICIPANTS: We studied 412 patients over 8
      months, classified into three groups: under 65years (control group, n=158), 65-80
      (n=186), and >80 (n=68). MEASUREMENTS: At admission: APACHE II, TISS-28 first
      day, Charlson Index, diagnosis, and prior Barthel Index. OUTCOME MEASURES: in
      hospital mortality, length of stay, discharge destination, and 2-year mortality
      and readmissions. Data analysis included multivariate logistic regression and
      receiver operating characteristics area under the curve (ROC AUC). RESULTS: No
      statistically significant differences between groups were observed in hospital
      mortality (14.1%), discharge to a long-term facility (2.7%), or 2-year
      readmissions (1.2+/-2.1). However, hospital stay was longer in patients aged 65
      80years (14 vs.10 days) and 2-year mortality was higher in those 65 or over (34%
      vs.10.6%). In the overall series in-hospital mortality was predicted by APACHE
      II, first-day TISS-28, and diagnosis (ROC AUC 0.81), and 2-year mortality by
      Charlson Index and age (ROC AUC 0.77). In the elderly patients 2-year mortality
      was predicted by Charlson and Barthel indices (ROC AUC 0.70). CONCLUSIONS:
      Illness severity and therapeutic intervention at admission to IMCU were
      predictors of short-term mortality, whereas the strongest predictor of long-term
      mortality was comorbidity. Our results suggest that comprehensive assessment of
      elderly patients at admission to IMCUs may improve outcome prediction.

PMID- 16791669
TI  - Application of pharmacokinetic-pharmacodynamic modelling in management of QT
      abnormalities after citalopram overdose.
AB  - OBJECTIVE: To develop guidelines for the management of QT prolongation after
      citalopram overdose, including decontamination with single-dose activated
      charcoal (SDAC) and cardiac monitoring. DESIGN: Simulation study using a
      previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted
      the time-course of QT prolongation and the effect of citalopram dose and use of
      SDAC on QT prolongation. MAIN MEASURES AND RESULTS: The previously developed PKPD
      model was used to address the following in patients following citalopram
      overdose: (1) Above what dose should patients be decontaminated? (2) Above what
      dose should patients have cardiac monitoring? (3) For what period of time should
      patients be monitored? The primary outcome was QT,RR combinations above an
      abnormal threshold as a surrogate predictor of torsades de pointes. Simulations
      were performed using MATLAB for an overdose patient with typical demographics: 30
      year-old female with a heart rate of 79 bpm taking citalopram therapeutically.
      The simulations showed: (1) There was significant benefit associated with the
      administration of SDAC to patients following citalopram overdose ingesting >600
      mg; (2) With citalopram overdoses >1,000mg it was advisable to give SDAC and
      cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR
      combinations was less than 1% in patients with normal QT,RR combinations up to 13
      h post-dose, so the minimum monitoring time for citalopram overdoses >1,000mg
      should be 13h. Recommended dose levels for intervention should be lowered in
      older patients and patients with tachycardia, while men are less sensitive to QT
      prolongation. CONCLUSIONS: Guidelines for the management of QT prolongation after
      citalopram overdose were developed. We believe the model will help clinicians to
      decide which patients to decontaminate and monitor.

PMID- 16791670
TI  - End-of-life care in India.

PMID- 16791671
TI  - Propofol in the treatment of refractory status epilepticus.
AB  - OBJECTIVES: To study prospectively the effects of propofol anesthesia on seizure
      control, hemodynamics and course of intensive care in patients with refractory
      status epilepticus. DESIGN AND SETTING: Prospective observational study in the
      general intensive care unit in a tertiary university hospital. PATIENTS: Ten
      patients with refractory status epilepticus. INTERVENTIONS: Patients received
      propofol anesthesia aiming to burst suppression EEG pattern for 12 h.
      MEASUREMENTS AND RESULTS: Dose of propofol, quality of burst suppression EEG,
      hemodynamics and the course of intensive care were recorded. Clinical and
      electrophysiological seizures terminated quickly, but maintaining burst
      suppression EEG pattern required incremental doses of propofol. Despite high
      doses of propofol, recovery from anesthesia was fast. CONCLUSIONS: High doses of
      propofol are needed in the treatment of refractory status epilepticus. The
      maintenance of continuous-burst suppression is difficult, and vigilant titrating
      of dosage of propofol is necessary under continuous EEG monitoring.

PMID- 16791672
TI  - Effects of a single-lung recruitment maneuver on the systemic release of
      inflammatory mediators.
AB  - OBJECTIVE: To study the hypothesis, that systemic levels of pro-inflammatory and
      anti-inflammatory cytokines may be affected by a single recruitment maneuver in
      mechanically ventilated patients. DESIGN: Prospective, interventional clinical
      trial. SETTING: Intensive care unit of a university hospital. PATIENTS: Sixteen
      mechanically ventilated patients with clinical and radiological signs of
      atelectasis. INTERVENTIONS: A single recruitment maneuver (RM) was performed by
      elevating the airway pressure to 40 cmH(2)O for 7s. MEASUREMENTS AND MAIN
      RESULTS: Plasmatic concentrations of interleukin (IL)-1beta, IL-6, IL-8, IL-10,
      IL-12p70 and tumor necrosis factor (TNF-alpha), arterial blood gases and
      hemodynamic parameters were measured immediately before and 5-360 min after the
      RM. The RM caused a minor, nevertheless significant improvement of oxygenation (p
      = 0.02) and carbon dioxide elimination (p=0.006) as well as a moderate drop of
      the mean arterial pressure (p=0.025). In contrast, plasma concentrations remained
      unaffected by the RM in all six mediators measured. CONCLUSION: A single
      inflation with an airway pressure of 40cmH(2)O for 7 s improved gas exchange only
      slightly and did not modify systemic levels of inflammatory mediators in
      mechanically ventilated patients with radiological evidence of atelectasis.

PMID- 16791673
TI  - Opiates at the end of life in an emergency department in Spain: euthanasia or
      good clinical practice?

PMID- 16791674
TI  - Assessing fluid responsiveness with esophageal Doppler dynamic indices: concepts
      and methods.

PMID- 16791675
TI  - The FTc is not an accurate marker of left ventricular preload.

PMID- 16791677
TI  - The "cross-talk phenomenon" in transpulmonary thermodilution is flow dependent.

PMID- 16791678
TI  - Community-acquired necrotizing fasciitis due to Pseudomonas aeruginosa.

PMID- 16791680
TI  - Comment on "Levels of vancomycin in the cerebral interstitial fluid after severe
      head injury" by Caricato et al.

PMID- 16791681
TI  - Early isovolemic hemofiltration in oliguric patients with septic shock.

PMID- 16791683
TI  - Atrial fibrillation in critical care.

PMID- 16791685
TI  - Grouping of accessions of Mexican races of maize revisited with SSR markers.
AB  - Mexican races of maize (Zea mays L.) represent a valuable genetic resource for
      breeding and genetic surveys. We applied simple sequence repeat (SSR) markers to
      characterize 25 accessions of races of maize from Mexico. Our objectives were to
      (1) study the molecular genetic diversity within and among these accessions and
      (2) examine their relationships as assumed previously on the basis of
      morphological data. A total of 497 individuals were fingerprinted with 25 SSR
      markers. We observed a high total number of alleles (7.84 alleles per locus) and
      total gene diversity (0.61), confirming the broad genetic base of the maize races
      from Mexico. In addition, the accessions were grouped into distinct racial
      complexes on the basis of a model-based clustering approach. The principal
      coordinate analyses of the four Modern Incipient hybrids corroborated the
      proposed parental races of Chalqueno, Conico Norteno, Celaya, and Bolita on the
      basis of the morphological data. Consequently, for some of the accessions,
      hybridizations provide a clue that can further be used to explain the
      associations among the Mexican races of maize.

PMID- 16791686
TI  - EST sequencing and phylogenetic analysis of the model grass Brachypodium
      distachyon.
AB  - Brachypodium distachyon (Brachypodium) is a temperate grass with the physical and
      genomic attributes necessary for a model system (small size, rapid generation
      time, self-fertile, small genome size, diploidy in some accessions). To increase
      the utility of Brachypodium as a model grass, we sequenced 20,440 expressed
      sequence tags (ESTs) from five cDNA libraries made from leaves, stems plus leaf
      sheaths, roots, callus and developing seed heads. The ESTs had an average trimmed
      length of 650 bp. Blast nucleotide alignments against SwissProt and GenBank non
      redundant databases were performed and a total of 99.9% of the ESTs were found to
      have some similarity to existing protein or nucleotide sequences. Tentative
      functional classification of 77% of the sequences was possible by association
      with gene ontology or clusters of orthologous group's index descriptors. To
      demonstrate the utility of this EST collection for studying cell wall
      composition, we identified homologs for the genes involved in the biosynthesis of
      lignin subunits. A subset of the ESTs was used for phylogenetic analysis that
      reinforced the close relationship of Brachypodium to wheat and barley.

PMID- 16791687
TI  - Extent and pattern of DNA methylation alteration in rice lines derived from
      introgressive hybridization of rice and Zizania latifolia Griseb.
AB  - We have reported previously that introgression by Zizania latifolia resulted in
      extensive DNA methylation changes in the recipient rice genome, as detected by a
      set of pre-selected DNA segments. In this study, using the methylation-sensitive
      amplified polymorphism (MSAP) method, we globally assessed the extent and pattern
      of cytosine methylation alterations in three typical introgression lines relative
      to their rice parent at approximately 2,700 unbiased genomic loci each
      representing a recognition site cleaved by one or both of the isoschizomers,
      HpaII/MspI. Based on differential digestion by the isoschizomers, it is estimated
      that 15.9% of CCGG sites are either fully methylated at the internal Cs and/or
      hemi-methylated at the external Cs in the rice parental cultivar Matsumae. In
      comparison, a statistically significant increase in the overall level of both
      methylation types was detected in all three studied introgression lines (19.2,
      18.6, 19.6%, respectively). Based on comparisons of MSAP profiles between the
      isoschizomers within the rice parent and between parent and the introgression
      lines, four major groups of MSAP banding patterns are recognized, which can be
      further divided into various subgroups as a result of inheritance of, or
      variation in, parental methylation patterns. The altered methylation patterns
      include hyper- and hypomethylation changes, as well as inter-conversion of hemi-
      to full-methylation, or vice versa, at the relevant CCGG site(s). Most
      alterations revealed by MSAP in low-copy loci can be validated by DNA gel blot
      analysis. The changed methylation patterns are uniform among randomly selected
      individuals for a given introgression line within or among selfed generations.
      Sequencing on 31 isolated fragments that showed different changing patterns in
      the introgression line(s) allowed their mapping onto variable regions on one or
      more of the 12 rice chromosomes. These segments include protein-coding genes,
      transposon/retrotransposons and sequences with no homology. Possible causes for
      the introgression-induced methylation changes and their implications for genome
      evolution and crop breeding are discussed.

PMID- 16791688
TI  - Connected populations for detecting quantitative trait loci and testing for
      epistasis: an application in maize.
AB  - Quantitative trait loci (QTL) detection experiments have often been restricted to
      large biallelic populations. Use of connected multiparental crosses has been
      proposed to increase the genetic variability addressed and to test for epistatic
      interactions between QTL and the genetic background. We present here the results
      of a QTL detection performed on six connected F(2) populations of 150 F(2:3)
      families each, derived from four maize inbreds and evaluated for three traits of
      agronomic interest. The QTL detection was carried out by composite interval
      mapping on each population separately, then on the global design either by taking
      into account the connections between populations or not. Epistatic interactions
      between loci and with the genetic background were tested. Taking into account the
      connections between populations increased the number of QTL detected and the
      accuracy of QTL position estimates. We detected many epistatic interactions,
      particularly for grain yield QTL (R(2) increase of 9.6%). Use of connections for
      the QTL detection also allowed a global ranking of alleles at each QTL. Allelic
      relationships and epistasis both contribute to the lack of consistency for QTL
      positions observed among populations, in addition to the limited power of the
      tests. The potential benefit of assembling favorable alleles by marker-assisted
      selection are discussed.

PMID- 16791689
TI  - The first gene-based map of Lupinus angustifolius L.-location of domestication
      genes and conserved synteny with Medicago truncatula.
AB  - We report the first gene-based linkage map of Lupinus angustifolius (narrow
      leafed lupin) and its comparison to the partially sequenced genome of Medicago
      truncatula. The map comprises 382 loci in 20 major linkage groups, two triplets,
      three pairs and 11 unlinked loci and is 1,846 cM in length. The map was generated
      from the segregation of 163 RFLP markers, 135 gene-based PCR markers, 75 AFLP and
      4 AFLP-derived SCAR markers in a mapping population of 93 recombinant inbred
      lines, derived from a cross between domesticated and wild-type parents. This
      enabled the mapping of five major genes controlling key domestication traits in
      L. angustifolius. Using marker sequence data, the L. angustifolius genetic map
      was compared to the partially completed M. truncatula genome sequence. We found
      evidence of conserved synteny in some regions of the genome despite the wide
      evolutionary distance between these legume species. We also found new evidence of
      widespread duplication within the L. angustifolius genome.

PMID- 16791690
TI  - Genetic mapping and BAC assignment of EST-derived SSR markers shows non-uniform
      distribution of genes in the barley genome.
AB  - A set of 111,090 barley expressed sequence tags (ESTs) was searched for the
      presence of microsatellite motifs [simple sequence repeat (SSRs)] and yielded
      2,823 non-redundant SSR-containing ESTs (SSR-ESTs). From this, a set of 754
      primer pairs was designed of which 525 primer pairs yielded an amplicon and as a
      result, 185 EST-derived microsatellite loci (EST-SSRs) were placed onto a genetic
      map of barley. The markers show a uniform distribution along all seven linkage
      groups ranging from 21 (7H) to 35 (3H) markers. Polymorphism information content
      values ranged from of 0.24 to 0.78 (average 0.48). To further investigate the
      physical distribution of the EST-SSRs in the barley genome, a bacterial
      artificial chromosomes (BAC) library was screened. Out of 129 markers tested, BAC
      addresses were obtained for 127 EST-SSR markers. Twenty-seven BACs, forming eight
      contigs, were hit by two or three EST-SSRs each. This unexpectedly high incidence
      of EST-SSRs physically linked at the sub-megabase level provides additional
      evidence of an uneven distribution of genes and the segmentation of the barley
      genome in gene-rich and gene-poor regions.

PMID- 16791691
TI  - Development of PCR-based allele-specific and InDel marker sets for nine rice
      blast resistance genes.
AB  - Blast resistance is one of the most important traits in rice breeding, and
      application of molecular markers for blast resistance breeding is likely to allow
      the rapid screening for the trait during early growth stages, without the need
      for inoculation of pathogen and phenotyping. Allele-specific PCR markers and
      insertion/deletion (InDel) markers, which genotype single-nucleotide
      polymorphisms and InDel polymorphisms, respectively, are useful tools for marker
      assisted selections. We developed sets of allele-specific PCR and InDel markers
      for nine rice blast resistance genes -- Piz, Piz-t, Pit, Pik, Pik-m, Pik-p, Pita,
      Pita-2, and Pib -- which are commonly used in Japanese blast resistance rice
      breeding programs. For each resistance gene, we used the segregation information
      from thousands of progeny in several crosses or published gene locations to
      generate a marker that cosegregated with the gene and markers that closely
      flanked the gene on either side. The developed cosegregating markers uniquely
      discriminated among each of the lines with the individual resistance genes
      (except for Pita and Pita-2). Therefore, these markers will likely facilitate the
      development of multiline cultivars carrying one or a combination of these nine
      blast resistance genes. In addition, the systems we developed may be valuable
      tools in the quality control of seed production from blast-resistant multiline
      cultivars.

PMID- 16791692
TI  - Phylogenetic analysis of the rDNA intergenic spacer subrepeats and its
      implication for the domestication history of foxtail millet, Setaria italica.
AB  - We sequenced ribosomal DNA intergenic spacer subrepeats and their flanking
      regions of foxtail millet landraces from various regions in Europe and Asia and
      its wild ancestor to elucidate phylogenetic differentiation within each of types
      I-III found in our previous work and to elucidate relationships among these three
      types. Type I was classified into seven subtypes designated as Ia-Ig based on
      subrepeat sequences; C repeats downstream of those subrepeats are also
      polymorphic. Of these, subtypes Ia-Id and Ig were found in foxtail millet
      landraces. Subtypes Ia and Ib were distributed broadly throughout Asia and
      Europe. Subtype Ic was distributed in China, Korea and Japan. Subtype Id has a 20
      bp deletion in subrepeat 3 and has a unique C repeat sequence. This subtype was
      found in a morphologically primitive landrace group from Afghanistan and
      northwestern Pakistan and differed greatly from other type I subtypes, implying
      that these landraces were domesticated independently. Subtypes Ig was found in a
      landrace from Pakistan and Ia and Ie-Ig were in six wild ancestor accessions.
      Type II was also highly polymorphic and four subtypes were found and designated
      as subtypes IIa-IId, but sequence analyses indicated type III as monomorphic. The
      present work indicates that type III should be classified as a subtype of type II
      (subtype IIe). Sequence polymorphism of subrepeats of types I-III indicated that
      subrepeats of subtype IIa are greatly divergent from others. Relationships among
      types I-III are much more complicated than anticipated based on previous RFLP
      work.

PMID- 16791693
TI  - Development of simple sequence repeat (SSR) markers and construction of an SSR
      based linkage map in Italian ryegrass (Lolium multiflorum Lam.).
AB  - In order to develop simple sequence repeat (SSR) markers in Italian ryegrass, we
      constructed a genomic library enriched for (CA)n-containing SSR repeats. A total
      of 1,544 clones were sequenced, of which 1,044 (67.6%) contained SSR motifs, and
      395 unique clones were chosen for primer design. Three hundred and fifty-seven of
      these clones amplified products of the expected size in both parents of a two-way
      pseudo-testcross F(1) mapping population, and 260 primer pairs detected genetic
      polymorphism in the F(1) population. Genetic loci detected by a total of 218
      primer pairs were assigned to locations on seven linkage groups, representing the
      seven chromosomes of the haploid Italian ryegrass karyotype. The SSR markers
      covered 887.8 cM of the female map and 795.8 cM of the male map. The average
      distance between two flanking SSR markers was 3.2 cM. The SSR markers developed
      in this study will be useful in cultivar discrimination, linkage analysis, and
      marker-assisted selection of Italian ryegrass and closely related species.

PMID- 16791695
TI  - QTL methodology for response curves on the basis of non-linear mixed models, with
      an illustration to senescence in potato.
AB  - The improvement of quantitative traits in plant breeding will in general benefit
      from a better understanding of the genetic basis underlying their development. In
      this paper, a QTL mapping strategy is presented for modelling the development of
      phenotypic traits over time. Traditionally, crop growth models are used to study
      development. We propose an integration of crop growth models and QTL models
      within the framework of non-linear mixed models. We illustrate our approach with
      a QTL model for leaf senescence in a diploid potato cross. Assuming a logistic
      progression of senescence in time, two curve parameters are modelled, slope and
      inflection point, as a function of QTLs. The final QTL model for our example data
      contained four QTLs, of which two affected the position of the inflection point,
      one the senescence progression-rate, and a final one both inflection point and
      rate.

PMID- 16791696
TI  - Single nucleotide polymorphic marker enabling rapid and early screening for the
      homoeolocus of beta-amylase-R1: a gene linked to copper efficiency on 5RL.
AB  - This study describes the development of a PCR marker to detect the beta-amylase
      R1 gene of rye. It provides an easy and rapid means for the identification of
      plants containing the beta-amylase-R1. Because rye chromosome segments do not
      normally recombine with wheat chromosomes, this marker provides a means for
      tracking all linked genes on that alien 5RL chromosome segment. Reaction
      conditions were optimised for an annealing temperature of 60 degrees C for a high
      stringency. The reaction was also optimised for low reaction volumes reducing the
      cost of the reagents required for the reaction. This PCR test can be used in
      breeding or mapping programs for the rapid screening of progeny containing
      translocations of 5RL and hence select for the copper efficiency trait of rye.

PMID- 16791694
TI  - MK17, a specific marker closely linked to the gynoecium suppression region on the
      Y chromosome in Silene latifolia.
AB  - The aim of this work was to isolate new DNA markers linked to the Silene
      latifolia Y chromosome. To do this we created a chromosome-specific plasmid
      library after DOP-PCR amplification of laser-microdissected Y-chromosomes. The
      library screening led to the isolation of several clones yielding mostly to
      exclusive male specific hybridization signals. Subsequent PCR confirmed the Y
      unique linkage for one of the sequences. This DNA sequence called MK17 has no
      homology to any known DNA sequence and it is not expressed. Based on PCR and
      Southern analyses, MK17 is present only in dioecious species of the Elisanthe
      section of the genus Silene (S. latifolia, S. dioica, and S. diclinis) and it is
      absent in related gynodioecious and hermaphroditic species. The mapping analysis
      using a panel of deletion mutants showed that MK17 is closely linked to the
      region controlling suppression of gynoecium development. Hence MK17 represents a
      valuable marker to isolate genes controlling the gynoecium development
      suppression on the Y chromosome of S. latifolia.

PMID- 16791697
TI  - Marker-assisted characterization of Asian wheat lines for resistance to Fusarium
      head blight.
AB  - The major quantitative trait locus (QTL) on 3BS from Sumai 3 and its derivatives
      has been used as a major source of resistance to Fusarium head blight (FHB)
      worldwide, but resistance genes from other sources are necessary to avoid
      complete dependence on a single source of resistance. Fifty-nine Asian wheat
      landraces and cultivars differing in the levels of FHB resistance were evaluated
      for type II FHB resistance and for genetic diversity on the basis of amplified
      fragment length polymorphism (AFLP) and simple sequence repeats (SSRs). Genetic
      relationships among these wheat accessions estimated by cluster analysis of
      molecular marker data were consistent with their geographic distribution and
      pedigrees. Chinese resistant landraces had broader genetic diversity than that of
      accessions from southwestern Japan. The haplotype pattern of the SSR markers that
      linked to FHB resistance quantitative trait loci (QTLs) on chromosomes 3BS, 5AS
      and 6BS of Sumai 3 suggested that only a few lines derived from Sumai 3 may carry
      all the putative QTLs from Sumai 3. About half of the accessions might have one
      or two FHB resistance QTLs from Sumai 3. Some accessions with a high level of
      resistance, may carry different FHB resistance loci or alleles from those in
      Sumai 3, and are worth further investigation. SSR data also clearly suggested
      that FHB resistance QTLs on 3BS, 5AS, and 6BS of Sumai 3 were derived from
      Chinese landrace Taiwan Xiaomai.

PMID- 16791698
TI  - A region of maize chromosome 2 affects response to downy mildew pathogens.
AB  - Quantitative trait loci (QTLs) for downy mildew resistance in maize were
      identified based on co-segregation with linked restriction fragment length
      polymorphisms or simple sequence repeats in 220 F2 progeny from a cross between
      susceptible and resistant parents. Disease response was assessed on F3 families
      in nurseries in Egypt, Thailand, and South Texas and after inoculation in a
      controlled greenhouse test. Heritability of the disease reaction was high (around
      93% in Thailand). One hundred and thirty polymorphic markers were assigned to the
      ten chromosomes of maize with LOD scores exceeding 4.9 and covering about 1,265
      cM with an average interval length between markers of 9.5 cM. About 90% of the
      genome is located within 10 cM of the nearest marker. Three putative QTLs were
      detected in association with resistance to downy mildew in different environments
      using composite interval mapping. Despite environmental and symptom differences,
      one locus on chromosome 2 had a major effect and explained up to 70% of the
      phenotypic variation in Thailand where disease pressure was the highest. The
      other two QTLs on chromosome 3 and chromosome 9 had minor effects; each explained
      no more than 4% of the phenotypic variation. The three QTLs appeared to have
      additive effects on resistance, identifying one major gene and two minor genes
      that contribute to downy mildew resistance.

PMID- 16791699
TI  - Characterisation of single nucleotide polymorphisms in sugarcane ESTs.
AB  - Commercial sugarcane cultivars (Saccharum spp. hybrids) are both polyploid and
      aneuploid with chromosome numbers in excess of 100; these chromosomes can be
      assigned to 8 homology groups. To determine the utility of single nucleotide
      polymorphisms (SNPs) as a means of improving our understanding of the complex
      sugarcane genome, we developed markers to a suite of SNPs identified in a list of
      sugarcane ESTs. Analysis of 69 EST contigs showed a median of 9 SNPs per EST and
      an average of 1 SNP per 50 bp of coding sequence. The quantitative presence of
      each base at 58 SNP loci within 19 contiguous sequence sets was accurately and
      reliably determined for 9 sugarcane genotypes, including both commercial
      cultivars and ancestral species, through the use of quantitative light emission
      technology in pyrophosphate sequencing. Across the 9 genotypes tested, 47 SNP
      loci were polymorphic and 11 monomorphic. Base frequency at individual SNP loci
      was found to vary approximately twofold between Australian sugarcane cultivars
      and more widely between cultivars and wild species. Base quantity was shown to
      segregate as expected in the IJ76-514 x Q165 sugarcane mapping population,
      indicating that SNPs that occur on one or two sugarcane chromosomes have the
      potential to be mapped. The use of SNP base frequencies from five of the
      developed markers was able to clearly distinguish all genotypes in the
      population. The use of SNP base frequencies from a further six markers within an
      EST contig was able to help establish the likely copy number of the locus in two
      genotypes tested. This is the first instance of a technology that has been able
      to provide an insight into the copy number of a specific gene locus in hybrid
      sugarcane. The identification of specific and numerous haplotypes/alleles present
      in a genotype by pyrophosphate sequencing or alternative techniques ultimately
      will provide the basis for identifying associations between specific alleles and
      phenotype and between allele dosage and phenotype in sugarcane.

PMID- 16791700
TI  - Anchoring of a large set of markers onto a BAC library for the development of a
      draft physical map of the grapevine genome.
AB  - Five hundred and six EST-derived markers, 313 SSR markers and 26 BAC end-derived
      or SCAR markers were anchored by PCR on a subset of a Cabernet Sauvignon BAC
      library representing six genome equivalents pooled in three dimensions. In
      parallel, the 12,351 EST clusters of the grapevine UniGene set (build #11) from
      NCBI were used to design 12,125 primers pairs and perform electronic PCR on
      67,543 nonredundant BAC-end sequences. This in silico experiment yielded 1,140
      positive results concerning 638 different markers, among which 602 had not been
      already anchored by PCR. The data obtained will provide an easier access to the
      regulatory sequences surrounding important genes (represented by ESTs). In total,
      1,731 islands of BAC clones (set of overlapping BAC clones containing at least
      one common marker) were obtained and 226 of them contained at least one
      genetically mapped anchor. These assigned islands are very useful because they
      will link the genetic map and the future fingerprint-based physical map and
      because they allowed us to indirectly place 93 ESTs on the genetic map. The
      islands containing two or more mapped SSR markers were also used to assess the
      quality of the integrated genetic map of the grapevine genome.

PMID- 16791701
TI  - Identification and mapping of Rf-I an inhibitor of the Rf5 restorer gene for Cms
      C in maize (Zea mays L.).
AB  - The restoration of the C-type cytoplasmic male sterility (Cms) has been a common
      agriculture practice in the production of hybrid seed for many years. In this
      study, a series of crosses between select sterile and restorer lines, as well as
      a backcross population of (Cms-C77 x 6233) x 6233, were used to investigate the
      restoration of C-type Cms. Our results demonstrated that there was an inhibitor
      of the Rf5 restorer gene. This inhibitor gene, Rf-I, maps to chromosome 7 and is
      tightly linked with SSR markers, umc2326 and umc2327, at a genetic distance 4.7
      and 3.4 cM, respectively. After analyzing our data combined with previous
      studies, we propose that the restoration of C-type Cms has two dominant genes,
      Rf4 and Rf5. Rf4 has the ability to restore all genotypes of Cms-C lines;
      however, there exists an inhibitor for the other restorer gene, Rf5; thus, it can
      restore only those genotypes of Cms-C lines lacking the Rf-I inhibitor.

PMID- 16791702
TI  - Quantitative trait loci for panicle size, heading date and plant height co
      segregating in trait-performance derived near-isogenic lines of rice (Oryza
      sativa).
AB  - Near-isogenic lines (NILs) are ideal materials for precise estimation of
      quantitative trait loci (QTL) effects and map-based gene isolation. With the
      completion of the rice genome sequence, QTL isolation based on NILs is becoming a
      routine. In this study, a trait-performance derived NIL strategy was adopted to
      develop NILs. Two plants were identified within one inbred line of recombinant
      inbred lines (RILs, F(7) generation), exhibiting a significant difference in
      panicle size. By marker screening of the whole genome the genetic background of
      the two plants was estimated to be 98.7% identical. These two plants were
      selected as parents to produce a near-isogenic F(2) (NIL-F(2)) population,
      consisting of 125 individuals, in which spikelets per panicle (SPP), grains per
      panicle (GPP), heading date (HD) and plant height (PH) were recorded. These four
      traits expressed discontinuous or bimodal distribution in the NIL-F(2) population
      and followed the expected segregation ratios for a single Mendelian factor by
      progeny tests. A partial dominant QTL for the four traits was mapped to the same
      interval flanked by RM310 and RM126 on chromosome 8. The QTL region explained
      83.0, 80.2, 94.9 and 93.8% of trait variation of SPP, GPP, HD and PH in the
      progenies, respectively. Progeny tests also confirmed co-segregation of QTL for
      the four traits, tall plants consistently flowering late and carrying large
      panicles. Different NILs development strategies are discussed.

PMID- 16791703
TI  - Age effects on anorectal pressure in anal continent women with lower urinary
      tract dysfunction.
AB  - The objective of this paper is to evaluate age and associated factors affecting
      anorectal pressure profilometry in anal-continent women with lower urinary tract
      symptoms. One hundred and ten anal-continent women (mean age, 47.7+/-12.8 years;
      range, 23-87 years) with lower urinary tract symptoms voluntarily participated in
      this study after undergoing a complete urogynecological evaluation including a
      multichannel urodynamic study. Anorectal pressure was evaluated by using a radial
      four-channel manometry with a water-filled catheter, which was placed 10 cm into
      the anorectum above the anal verge. We divided the anorectal pressure profile
      into five segments and four axes to clarify the axis-specific defect or site
      specific damage in the sphincter profile. The aging process had a negative effect
      on the peak resting pressure from the 41 to 100th percentile of the anorectal
      pressure profile at 12 o'clock, 3 o'clock, and 6 o'clock (P<0.05). With voluntary
      squeezing, aging had negative effects on the peak squeeze pressure from the 41 to
      100th percentile of the anorectal pressure profile at 3 o'clock, and 61 to 80
      percentile at 12 o'clock (P<0.05). There is a trend where anorectal pressure
      reduces as a woman ages, especially at the anal sphincter area in women with
      lower urinary tract symptoms. The anterior and left sides of the anorectal
      sphincter seem to be the most vulnerable in the aging process.

PMID- 16791704
TI  - Medium-term efficacy of pelvic floor muscle training for female urinary
      incontinence in daily practice.
AB  - The purpose of this paper is to assess the efficacy of physiotherapy and quality
      of life in women treated for urinary incontinence by specialized physiotherapists
      in daily community-based practices. Three hundred and fifty-five women were
      treated in five physiotherapy practices between January 2000 and December 2004.
      After a minimum follow-up of 12 months, these women received a questionnaire at
      home. With the questionnaire, we collected demographic data, data on the efficacy
      of treatment, satisfaction with the result, and the Urogenital Distress
      Inventory, and Incontinence Impact Questionnaire. Additional information was
      derived from the medical files. One hundred and eighty-seven women responded.
      Fifty percent of women were satisfied with the result of physiotherapy. After a
      mean follow-up of 32 months, 123 out of 130 women (94.6%), who only had
      physiotherapy, recorded to experience incontinence episodes daily to several
      times a week. Women who underwent additional incontinence surgery after
      insufficient physiotherapy recorded significantly less urinary incontinence
      symptoms and a better quality of life. Pelvic floor muscle training for urinary
      incontinence is effective in half of the women. If not successful, women seem to
      benefit significantly from incontinence surgery.

PMID- 16791705
TI  - The empty bladder.
AB  - The empty (near-empty) bladder can have a volume ranging from 0 to 30 ml. Its
      diagnosis is effectively and least invasively made by ultrasound (transvaginal
      superior). It is a key marker of normal bladder function. It is necessary for the
      accurate assessment of uterovaginal prolapse, as increasing bladder volume has
      been shown to reduce the extent of the prolapse. Any negative effect of prolapse
      on voiding is reduced at high bladder volumes compared to voiding from low
      bladder volumes (due to the same reduction in the extent of the prolapse). An
      empty bladder is optimal for bimanual pelvic examination and most transvaginal
      ultrasound examinations including that for uterine version. The retroverted
      uterus is proving to be of increasing relevance to prolapse. The woman whose
      bladder is empty post-voiding is at a significantly lower risk of recurrent
      urinary tract infections. The bladder that can't be emptied is a marker of
      bladder dysfunction, requiring a fuller investigation. From a surgical point of
      view, the empty bladder improves access and reduces surgical risks with
      laparotomy, as well as both laparoscopic and vaginal surgery.

PMID- 16791708
TI  - Tissue endostatin correlates inversely with capillary network in rat heart and
      skeletal muscles.
AB  - The role of angiostatic factors, including endostatin, in regulating
      physiological angiogenesis is poorly understood. We used normal adult rats under
      physiological resting conditions to examine the relationship between tissue
      endostatin, VEGF, and capillary density (CD) in the heart (high metabolic
      activity) versus the skeletal muscle (relatively low metabolic activity). The
      heart (left ventricle, LV) and skeletal muscle (anterior tibialis, AT) were
      dissected from 12-week-old male Sprague-Dawley rats. Transverse cryosections of
      LV and AT were stained with FITC-conjugated GS-I-lectin. CD was determined by
      analysis of randomly acquired digital images of the cryosections using Optimas
      software. Tissue protein levels of endostatin and VEGF were determined by ELISA
      assays. Tissue endostatin levels were lower in the LV and higher in the AT (135
      +/- 39 vs. 663 +/- 114 pg/mg) and VEGF levels were higher in the LV and lower in
      the AT (41 +/- 3 vs. 27 +/- 4 pg/mg), respectively (n = 7, P < 0.01). CD in LV
      and AT were 3632 +/- 428 and 437 +/- 44/mm2, respectively (P < 0.01). We
      demonstrated that an 8.3-fold greater capillary density is related to a 4.9-fold
      lower level of tissue endostatin and a 1.5-fold higher level of tissue VEGF in
      the heart (LV) versus the skeletal muscle (AT) of normal rats under physiological
      resting conditions. Also, exercise training increased capillary density,
      decreased tissue endostatin and increased tissue VEGF in the skeletal muscle
      (AT). These findings suggest that tissue endostatin content correlates inversely
      with capillary network in the muscle tissues with different metabolic activity,
      and that tissue endostatin may play a very important role in the metabolic
      control of angiogenesis under physiological conditions.

PMID- 16791706
TI  - The effect of cyclooxygenase-2 inhibitors on bone mineral density: results from
      the Canadian Multicentre Osteoporosis Study.
AB  - INTRODUCTION: The use of cyclooxygenase-2 (COX-2) inhibitors has been
      demonstrated to not only impair load-induced bone formation but also prevent
      menopause-associated bone loss. We hypothesized that COX-2 inhibitor use would be
      associated with increased bone mineral density (BMD) in postmenopausal women not
      using estrogen therapy and, conversely, with decreased BMD in men. METHODS: The
      Canadian Multicentre Osteoporosis Study is a longitudinal, randomly selected,
      population-based community cohort. We present data from men (n=2,004) and
      postmenopausal women age 65 and older (n=2,776) who underwent a BMD measurement
      and structured interview in the 5th year of the study. The outcome measure was
      percent difference in BMD (g/cm(2)). RESULTS: Daily COX-2 inhibitor use was
      reported by 394 subjects. In men, daily use of COX-2 inhibitors was associated
      with a lower BMD at all hip sites, with a percent difference of -3.1% [95%
      confidence interval (CI), -6.0, -0.3] between users and nonusers at total hip. In
      postmenopausal women not using estrogen replacement therapy, daily COX-2
      inhibitor use was associated with higher BMD at most sites [percent difference at
      total hip: +3.0% (95% CI, 0.3, 5.8)]. These effects appeared to be dose
      dependent. CONCLUSION: COX-2 inhibitor use was associated with a lower BMD in men
      and, on the other hand, with a higher BMD in postmenopausal women not using
      estrogen replacement therapy. Men who have used COX-2 inhibitors may wish to seek
      BMD measurement to assess their fracture risk. However, COX-2 inhibitors may have
      utility in postmenopausal women if bone-selective analogs can be developed.

PMID- 16791709
TI  - Distribution of nitrogen species in groundwater aquifers of an industrial area in
      alluvial Indo-Gangetic Plains--a case study.
AB  - The groundwater samples collected from the shallow and deep groundwater aquifers
      of an industrial area of the Kanpur city (Uttar Pradesh, India) were analyzed for
      the concentration levels and distribution pattern of nitrogenous species, such as
      nitrate-nitrogen (NO(3)-N), nitrite-nitrogen (NO(2)-N), ammonical-nitrogen (NH(4)
      N), organic-nitrogen (Org-N) and total Kjeldahl-nitrogen (TKN) to identify the
      possible contamination source. Geo-statistical approach was adopted to determine
      the distribution and extent of the contaminant plume. In the groundwater aquifers
      NO(3)-N, NO(2)-N, NH(4)-N, TKN, Org-N and Total-N ranged from 0.10 to 64.10, BDL
      (below detection limit)-6.57, BDL-39.00, 7.84-202.16, 1.39-198.97 and 8.89-219.43
      mg l(-1), respectively. About 42% and 26% of the groundwater samples of the
      shallow and deep groundwater aquifers, respectively, exceeded the BIS (Bureau of
      Indian Standards) guideline value of 10 mg l(-1) for NO(3)-N and may pose serious
      health hazards to the people of the area. The results of the study revealed that
      the groundwater aquifers of the study area are highly contaminated with the
      nitrate and indicates point source pollution of nitrate in the study area.

PMID- 16791710
TI  - A screening-level assessment of lead, cadmium, and zinc in fish and crayfish from
      Northeastern Oklahoma, USA.
AB  - The objective of this study was to evaluate potential human and ecological risks
      associated with metals in fish and crayfish from mining in the Tri-States Mining
      District (TSMD). Crayfish (Orconectes spp.) and fish of six frequently consumed
      species (common carp, Cyprinus carpio; channel catfish, Ictalurus punctatus;
      flathead catfish, Pylodictis olivaris; largemouth bass, Micropterus salmoides;
      spotted bass, M. punctulatus; and white crappie, Pomoxis annularis) were
      collected in 2001--2002 from the Oklahoma waters of the Spring River (SR) and
      Neosho River (NR), which drain the TSMD. Samples from a mining-contaminated site
      in eastern Missouri and from reference sites were also analyzed. Individual fish
      were prepared for human consumption in the manner used locally by Native
      Americans (headed, eviscerated, and scaled) and analyzed for lead, cadmium, and
      zinc. Whole crayfish were analyzed as composite samples of 5--60 animals. Metals
      concentrations were typically higher in samples from sites most heavily affected
      by mining and lowest in reference samples. Within the TSMD, most metals
      concentrations were higher at sites on the SR than on the NR and were typically
      highest in common carp and crayfish than in other taxa. Higher concentrations and
      greater risk were associated with fish and crayfish from heavily contaminated SR
      tributaries than the SR or NR mainstems. Based on the results of this and
      previous studies, the human consumption of carp and crayfish could be restricted
      based on current criteria for lead, cadmium, and zinc, and the consumption of
      channel catfish could be restricted due to lead. Metals concentrations were
      uniformly low in Micropterus spp. and crappie and would not warrant restriction,
      however. Some risk to carnivorous avian wildlife from lead and zinc in TSMD fish
      and invertebrates was also indicated, as was risk to the fish themselves.
      Overall, the wildlife assessment is consistent with previously reported
      biological effects attributed to metals from the TSMD. The results demonstrate
      the potential for adverse effects in fish, wildlife, and humans and indicate that
      further investigation of human health and ecological risks, to include additional
      exposure pathways and endpoints, is warranted.

PMID- 16791711
TI  - Biomineralogy of human urinary calculi (kidney stones) from some geographic
      regions of Sri Lanka.
AB  - Kidney stones (urinary calculi) have become a global scourge since it has been
      recognized as one of the most painful medical problems. Primary causative factors
      for the formation of these stones are not clearly understood, though they are
      suspected to have a direct relationship to the composition of urine, which is
      mainly governed by diet and drinking water. Sixty nine urinary calculi samples
      which were collected from stone removal surgeries were analyzed chemically for
      their Na, K, Ca, Mg, Cu, Zn, Pb, Fe and phosphate contents. Structural and
      mineralogical properties of stones were studied by XRD and FT-IR methods. The
      mean contents of trace elements were 1348 mg kg(-1) (Na); 294 mg kg(-1) (K); 32%
      (Ca); 1426 mg kg(-1) (Mg); 8.39 mg kg(-1) (Mn); 258 mg kg(-1) (Fe); 67 mg kg(-1)
      (Cu); 675 mg kg(-1) (Zn); 69 mg kg(-1) (Pb); and 1.93% (PO (4) (3-) ). The major
      crystalline constituent in the calculi of Sri Lanka is calcium oxalate
      monohydrate. Principal component analysis was used to identify the multi element
      relationships in kidney stones. Three components were extracted and the first
      component represents positively correlated Na-K-Mg-PO (4) (3-) whereas the second
      components represent the larger positively weighted Fe-Cu-Pb. Ca-Zn correlated
      positively in the third component in which Mn-Cu correlated negatively. This
      study indicates that during the crystallization of human urinary stones, Ca shows
      more affinity towards oxalates whereas other alkali and alkaline earths
      precipitate with phosphates.

PMID- 16791712
TI  - Blocking of striated muscle degeneration by serotonin in C. elegans.
AB  - Prevention of muscle fiber degeneration is a key issue in the treatment of
      muscular dystrophies such as Duchenne Muscular Dystrophy (DMD). It is widely
      postulated that existing pharmaceutical compounds might potentially be beneficial
      to DMD patients, but tools to identify them are lacking. Here, by using a
      Caenorhabditis elegans model of dystrophin-dependent muscular dystrophy, we show
      that the neurohormone serotonin and some of its agonists are potent suppressors
      of muscle degeneration. Inhibitors of serotonin reuptake transporters, which
      prolong the action of endogenous serotonin, have a similar effect. Moreover,
      reduction of serotonin levels leads to degeneration of non-dystrophic muscles.
      Our results demonstrate that serotonin is critical to C. elegans striated
      muscles. These findings reveal a new function of serotonin in striated muscles.

PMID- 16791713
TI  - Acute myocardial infarction during high-dose methylprednisolone therapy for
      Graves' ophthalmopathy.
AB  - Management of Graves' ophthalmopathy includes high-dose glucocorticoids.
      Glucocorticoids may have many side effects, and therefore their use should always
      be carefully considered. Here we present the case of a woman who received high
      doses of methylprednisolone (1 g iv daily) for active Graves' ophthalmopathy, and
      developed severe hypertension followed by myocardial infarction on the fifth day
      of treatment. Before the myocardial infarction, the patient was in good
      condition, normotensive, non-diabetic, non-obese. Except hypothyroidism after
      radioiodine treatment (euthyroid under substitutional therapy), she suffered from
      no other diseases. There had been one episode of chest discomfort in her past
      history. We conclude that myocardial infarction may develop in patients treated
      with high-dose glucocorticoids for Graves' ophthalmopathy, and increased blood
      pressure may herald this complication.

PMID- 16791714
TI  - Variations in small-volume doses of a liquid antibiotic using two paediatric
      administration devices.
AB  - OBJECTIVE: Children can be a difficult population in which to administer
      medicines and many parents or caregivers may be inexperienced in the
      administration of paediatric medicines. The aim of this study was to determine
      the variations in volumes of doses of reconstituted antibiotic suspension using
      two calibrated administrative devices. SETTING: Measurements were conducted in a
      Dispensing Laboratory in New Zealand, using locally available commercial,
      standardized measuring devices. METHOD: A medicine dropper and a spill-proof
      measuring spoon were selected and a dose of 3 ml, to be given three times daily
      for five days (45 ml) was used for the purposes of this study. Doses were weighed
      and corresponding volumes were calculated using the average weight per ml.
      RESULTS: The doses measured using the medicine dropper were consistently smaller
      than the doses measured using the spill-proof measuring spoon. CONCLUSION: The
      current method of financial subsidy for the provision of liquid antibiotics in
      New Zealand should be investigated. Pharmacists must ensure that an appropriate
      measure and sufficient quantity is provided for optimal duration of treatment.
      This study contributes to the relatively sparse information available on the
      administration of children's medicines. It will have relevance for countries
      where pharmacy practice is determined largely by administrative departments.

PMID- 16791715
TI  - Improving access to essential drugs for rural communities in Nigeria: the Bamako
      initiative re-visited.
AB  - One of the major indices of the performance of the primary healthcare delivery
      remains improved access to essential drugs. The Bamako Initiative (BI) was
      introduced by WHO/UNICEF in the late 1980's to improve access to essential drugs
      for the most vulnerable in the society and thus improve the health outcomes.
      However, almost 20 years post-inception, the outcomes and/or impact of the BI on
      the health indices of many implementing African countries remains varied, with
      not so significant improvement in health status being registered in a majority of
      countries. A review of literature suggests that the poor outcomes may be
      attributable to issues more fundamental than just the absence of adequate
      funding. Although the current Nigeria Drug Policy (NDP) clearly enunciates and
      provides policy direction for the core objective of the Bamako Initiative (BI),
      which is "EQUITABLE ACCESS TO ESSENTIAL DRUGS at the community level", it appears
      the implementation guidelines may not have drawn on the NDP policy guidelines to
      provide an adequate framework/tools to ensure efficient realization of the core
      objectives of the BI. This paper appraises the implementation of the BI in
      Nigeria within the context of the NDP. It reviews the current status of the BI in
      the country and attempts to proffer solutions for improvement and/or
      functionality. The paper seeks:1. To provoke thoughts and direct attention to an
      aspect of Public Health Pharmacy, which had been hitherto neglected by
      Pharmacists and Programme Planners.2. To get pharmacists more involved in
      ensuring the efficiency and safety of drug supply at the community level.3. To
      engender more research by pharmacists and stakeholders for improved outcomes in
      this service area.

PMID- 16791716
TI  - Risks and concerns about supplementary prescribing: survey of primary and
      secondary care pharmacists.
AB  - OBJECTIVE (OF THE STUDY): To provide data on the views of chief pharmacists (CPs)
      and primary care trust pharmacists (PCTPs) on the risks and concerns surrounding
      supplementary prescribing. SETTING: Secondary and primary care within England.
      METHOD: Postal questionnaire surveys of chief pharmacists and primary care trust
      pharmacists. MAIN OUTCOME MEASURE: Significance of the association between the
      extracted factors. RESULTS: The response rate was 68% for both the primary care
      (183/271) and secondary care surveys (97/143). The survey tool was subjected to
      factor analysis and reliability testing. For both sectors, the three factors that
      were extracted described concerns over the training model for supplementary
      prescribing, concerns about the professional competency/responsibility of the
      supplementary prescribers once trained, and positivity about the implementation
      of supplementary prescribing. For both sectors, as trusts have more experience of
      supplementary prescribing by nurses, the respondents had less concerns about the
      supplementary prescribing training model. For secondary care, as the total number
      of pharmacists employed within the trust increases, the respondents had less
      concerns over the limitations of the supplementary prescribing training model.
      CONCLUSION: Although both sectors have concerns over the training model for
      supplementary prescribing and also professional competence and responsibility
      once trainees qualify, there is overall a positive attitude towards supplementary
      prescribing and there is a belief that pharmacists wish to take this role on.

PMID- 16791717
TI  - A pharmacotherapy follow-up program in patients with type-2 diabetes in community
      pharmacies in Spain.
AB  - OBJECTIVE: Poor metabolic control and high associated morbidity and mortality
      among type 2 diabetic patients require a level of care from the pharmacist that
      goes beyond usual dispensing. The aim of the present study was to evaluate the
      improvement in metabolic control, the resolution of drug-related problems (DRPs)
      and the increase in patient awareness of diabetes as outcomes of a
      pharmacotherapy follow-up program in type 2 diabetic patients. METHOD: Randomized
      controlled trial conducted in 14 community pharmacies in the province of
      Pontevedra (Spain) with 112 patients between February 2003 and March 2004. The
      control group received the usual care, and the intervention group patients were
      included in a pharmacotherapy follow-up program. This individualized program,
      which consists of the detection and resolution of DRPs and diabetes education,
      involves patients in their own care in order to obtain maximum benefit from the
      medication they use. MAIN OUTCOME MEASURES: HbA(1c), Fasting Blood Glucose (FBG),
      lipid profile, blood pressure, body mass index (BMI), DRPs and knowledge were
      evaluated at the onset of the program and periodically until conclusion. RESULTS:
      There was a significant difference in changes from baseline between the
      intervention and the control group in DRPs (1.7+/-1.2 versus 3.1+/-1.2 P<0.0001),
      knowledge (17.9+/-3.7 versus 11.4+/-6.7 points P<0.0001), HbA(1c) (7.9+/-1.7
      versus 8.5+/-1.9% P<0.0001), FBG (154+/-61.3 versus 168+/-57.8 mg/dl P=0.0004),
      total cholesterol (202+/-41.5 versus 217+/-43.5 mg/dl P=0.0054) and SBP (135+/
      16.4 versus 150+/-19.9 mmHg P=0.0006). CONCLUSIONS: A substantial number of
      patients showed an improvement in their outcomes for the chosen metabolic
      indicators. Pharmacotherapy follow-up programs conducted by community pharmacists
      can play an important role in achieving therapeutic goals in patients with type 2
      diabetes. This study shows that the incorporation of type 2 diabetic patients in
      a pharmacotherapy follow-up program may contribute to achieve positive clinical
      outcomes and will contribute to the implementation and progress of
      pharmacotherapy follow-up programs in community pharmacies.

PMID- 16791718
TI  - Polyclonal antibody against a recombinant chlorotoxin-like peptide from the
      Chinese scorpion and detection of its putative receptors in human glioma cells.
AB  - The nucleotide sequence of a type of chlorotoxin-like peptide, an inhibitor of
      small-conductance Cl(-) channels, from the scorpion, Buthus martensii Karsch, was
      synthesized (named rBmK CTa) according to the sequence optimized for codon usage
      in E. coli. It was over-expressed using a pExSecI expression system and purified
      to homogeneity. Polycolonal antibodies to the purified protein were raised in
      rats. Overlay assay and pull-down assay showed that this toxin specially binds to
      two proteins in the glioma cells with corresponding molecular weights of about 80
      and 35 kDa. They may serve as candidate receptors or alternative cellular
      component for interaction with rBmK CTa.

PMID- 16791719
TI  - Response of growth and fatty acid compositions of Nannochloropsis sp. to
      environmental factors under elevated CO2 concentration.
AB  - Nannochloropsis sp. was grown with different levels of nitrate, phosphate,
      salinity and temperature with CO(2) at 2,800 microl l(-1). Increased levels of
      NaNO(3) and KH(2)PO(4) raised protein and polyunsaturated fatty acids (PUFAs)
      contents but decreased carbohydrate, total lipid and total fatty acids (TFA)
      contents. Nannochloropsis sp. grew well at salinities from 22 to 49 g l(-1), and
      lowering salinity enhanced TFA and PUFAs contents. TFA contents increased with
      the increasing temperature but PUFAs contents decreased. The highest
      eicosapentaenoic acid (EPA, 20:5 omega3) content based on the dry mass was above
      3% under low N (150 microM NaNO(3)) or high N (3000 microM NaNO(3)) condition.
      Excessive nitrate, low salinity and temperature are thus favorable factors for
      improving EPA yields in Nannochloropsis sp.

PMID- 16791721
TI  - Increase of the hydrophilicity of polyethylene terephthalate fibres by hydrolases
      from Thermomonospora fusca and Fusarium solani f. sp. pisi.
AB  - Treatment of polyethylene terephthalate fibres with hydrolase preparations from
      Thermomonospora (Thermobifida) fusca and Fusarium solani f. sp. pisi resulted in
      an increase of the hydrophilicity of the fibres determined by measurement of
      their dyeing behaviour with reactive dyes and their water absorption ability.
      Reflectance spectrometry of treated fibres dyed with a reactive dye showed that
      the colour became more intense corresponding to an increase of hydroxyl groups on
      the fibre surfaces and indicated a stepwise peeling of the fibres by the enzymes
      comparable to the effects obtained by alkaline treatments. The synthetic fibres
      treated with the hydrolase from T. fusca also showed enhanced water absorption
      ability further confirming the increased surface hydrophilicity caused by the
      enzyme.

PMID- 16791722
TI  - Tailored recombinant elastin-like polymers for advanced biomedical and
      nano(bio)technological applications.
AB  - The genetic engineering of protein-based polymers is a method that enables, in an
      easy way, the design of complex and highly functional macromolecules. As examples
      of this approach, different molecular designs are presented, with increasing
      degree of complexity, showing how the controlled increase in their complexity
      yields (multi)functional materials with more selected and sophisticated
      properties. The simplest designs show interesting properties already, but the
      adequate introduction of given chemical functions along the polymer chain
      provides an opportunity to expand the range of properties to enhanced smart
      behavior and self-assembly. Finally, examples are given where those molecular
      designs further incorporate selected bioactivities in order to develop materials
      for the most cutting edge applications in biomedicine and nano(bio)technology.

PMID- 16791723
TI  - Transglutaminase reactivity with gelatine: perspective applications in tissue
      engineering.
AB  - Gelatine was crosslinked by means of an enzymatic treatment using tissue
      transglutaminase (tTGase) (Sigma) and microbial transglutaminase (mTGase)
      (Ajinomoto) which catalyses the formation of isopeptide bonds between the gamma
      carbonyl group of a glutamine residue and the epsilon-amino group of a lysine
      residue. The reaction is an interesting alternative to the traditional
      glutaraldehyde crosslinking, which has several drawbacks (e.g., in medical
      application) due to the toxicity of the chemical reagent. To further investigate
      the possibility to utilize the modified protein for tissue engineering
      application, TGase crosslinked gelatine was incorporated in a gellan matrix, a
      polysaccharide, to enhance the stability in aqueous media. Films obtained by
      casting were characterized by thermal analysis, chemical imaging, swelling
      behaviour and cell adhesion.

PMID- 16791724
TI  - A new cuticle scale hydrolysing protease from Beauveria brongniartii.
AB  - From a screening for the production of new proteases specific for cuticle scales,
      Beauveria brongniartii was selected producing an alkaline Ca(++) dependent
      protease. The purified had a molecular weight of 27 kDa and a pI value of 8.0.
      Substrate specificities of model substrates (wool with partially removed cuticles
      treated with SDS) were analyzed by protein release, dissolved organic carbon
      (DOC) and nitrogen analysis. The C/N ratio of released material turned out to be
      a good parameter to determine the site of action of proteases on fibres. Compared
      to other enzymes, the fungal protease preferentially hydrolyzed cuticle scales
      and has thus a potential for anti-shrinking pre-treatment of wool fabrics.

PMID- 16791725
TI  - New enzyme-based process direction to prevent wool shrinking without substantial
      tensile strength loss.
AB  - In this paper a new enzymatic process direction is described for obtaining
      machine washable wool with acceptable quality. In general, application of
      protease enzyme technology in wool processing results in considerable loss of
      tensile strength by diffusion of the enzyme into the interior of wool fibers. To
      overcome this disadvantage enzymatic activity has been more targeted to the outer
      surface of the scales by improving the susceptibility of the outer surface scale
      protein for proteolytic degradation. This has been realized by a pretreatment of
      wool with hydrogen peroxide at alkaline pH in the presence of high concentrations
      of salt.

PMID- 16791726
TI  - An ethoxylated alkyl phosphate (anionic surfactant) for the promotion of
      activities of proteases and its potential use in the enzymatic processing of
      wool.
AB  - Pretreatments of wool fabrics with cationic, anionic or non-ionic surfactants
      were investigated to reduce surface tension and improve the wettability of the
      fibres in order to promote protease activity on the fibres in subsequent
      processes. Results showed that an ethoxylated alkyl phosphate (specific anionic
      surfactant) as well as the widely used non-ionic surfactant was compatible with
      proteases in the enzymatic treatment of wool. There is therefore a potential for
      using specific anionic surfactants to achieve efficient enzymatic scouring
      processes.

PMID- 16791727
TI  - Detergent formulations for wool domestic washings containing immobilized enzymes.
AB  - The stability of immobilized and native Esperase, a commercial serine protease,
      was studied by incubating the enzymes in four formulations containing the same
      amount of anionic and non-ionic surfactants. The results show that the activity
      of the immobilized enzyme is not affected by the presence of detergents while the
      native enzyme lost 50% of activity after 20 min of incubation in these four
      formulations. The washing performance of the detergents prepared with the
      immobilized Esperase was studied on cotton and wool fabric samples stained with
      human blood and egg yolk, using as control the detergent containing native
      Esperase. The best stain removal for cotton samples stained with human blood was
      achieved using the detergent with immobilized Esperase. Several physical tests
      confirmed that wool keratin was not degraded by the immobilized Esperase,
      validating the ability to use formulated detergents containing this immobilized
      enzyme for safe wool domestic washing.

PMID- 16791728
TI  - Kinetic studies of reactive azo dye decolorization in anaerobic/aerobic
      sequencing batch reactors.
AB  - The decolorization kinetics of Remazol Brilliant Violet 5R (RBV-5R) and Remazol
      Black B (RB-B) (mono- and diazo reactive dyes, respectively) was investigated in
      the first 9 h (anaerobic phase) of a 24-h cycle anaerobic/aerobic sequencing
      batch reactor (SBR). Two distinct, successive decolorization periods were
      observed for both dyes, apparently due to different decolorization mechanisms.
      The apparent first-order rate constants were much lower for the second periods.
      First-order kinetics were apparently followed for both periods of RBV-5R but not
      for the first decolorization period of RB-B, possibly due to the occurrence of
      mass transfer limitations.

PMID- 16791729
TI  - Specificities of a chemically modified laccase from Trametes hirsuta on soluble
      and cellulose-bound substrates.
AB  - Laccases could prevent fabrics and garments from re-deposition of dyes during
      washing and finishing processes by degrading the solubilized dye. However,
      laccase action must be restricted to solubilized dye molecules thereby avoiding
      decolorization of fabrics. Chemical modification of enzymes can provide a
      powerful tool to change the adsorption behaviour of enzymes on water insoluble
      polymers. Polyethylene glycol (PEG) was covalently attached onto a laccase from
      Trametes hirsuta. Different molecular weights of the synthetic polymer were
      tested in terms of adsorption behaviour and retained laccase activity. Covalent
      attachment of PEG onto the laccase resulted in enhanced enzyme stability while
      with increasing molecular weight of attached PEG the substrate affinity for the
      laccase conjugate decreased. The activity of the modified laccases on fibre bound
      dye was drastically reduced decreasing the adsorption of the enzyme on various
      fabrics. Compared to the 5 kDa PEG laccase conjugate (K/S value 47.60) the K/S
      value decreased much more (47.96-46.35) after the treatment of dyed cotton
      fabrics with native laccase.

PMID- 16791730
TI  - Degradation of lignin-containing materials by xylanase in biopreparation of
      cotton.
AB  - Solubilization of lignin and carbohydrates from the lignin-holocellulose
      structure of cotton seed-coat fragments was investigated by UV/VIS spectrometry.
      Xylanase (Pulpzyme HC) pre-treatment partially destroyed the lignocellulosic
      structure of the seed-coat fragments, producing reducing sugars and soluble
      lignin in the supernatant. Furthermore, the pre-treatment by enzyme enhanced the
      delignification in the subsequent alkaline scouring process and increased the
      lightness of the substrate.

PMID- 16791731
TI  - Laccase-assisted dyeing of cotton.
AB  - Cotton cellulose was dyed "in situ" with a polymeric dye generated by oxidative
      coupling of colourless 2,5-diaminobenzenesulfonic acid and 1-hydroxyphenol
      (catechol) with laccase. Up to 70% dye fixation was obtained increasing the
      concentration of catechol less soluble upon oxidation from 1 to 10 mmol, while 1
      mmol of diamine was used. Dye fixation was not achieved using equal molar
      concentrations of the reagents.

PMID- 16791732
TI  - Enzymes in bast fibrous plant processing.
AB  - The program COST Action 847 Textile Quality and Biotechnology (2000-2005) has
      given an excellent chance to review the possibilities of the research, aiming at
      development of the industrial application of enzymes for bast fibrous plant
      degumming and primary processing. The recent advancements in enzymatic processing
      of bast fibrous plants (flax, hemp, jute, ramie and alike plants) and related
      textiles are given. The performance of enzymes in degumming, modification of bast
      fibres, roving, yarn, related fabrics as well as enzymatic bonding of
      lignocellulosic composites is provided.

PMID- 16791733
TI  - Evolution of homochirality by epimerization of random peptide chains. A
      stochastic model.
AB  - A cyclic process is described which is constituted of polymerization,
      epimerization, and hydrolysis steps. During the first cycle peptides with random
      sequences are formed from racemic amino acids. A small portion of these peptides
      have substructures with a terminal residue linked to a homochiral sequence of
      optical antipodes. In such a substructure the terminal residue is assumed to
      invert into its mirror image so that a thermodynamically favourable epimeric
      stucture with continuous homochirality is formed. In the hydrolysis step the
      peptides are split back to monomeric units with retention of configuration. Due
      to stochastic differences between L- and D-substructures a net excess of one of
      the enantiomers results. This excess enhances the probability of the formation of
      substructures having the dominant configuration in the next cycle. It is shown by
      probabilistic considerations and computer simulations that this mechanism
      generates an autocatalytic growth of one of the enantiomers which finally results
      in homochiral populations of amino acids. The number of cycles necessary to
      attain homochirality depends on the number of residues of the substructure, on
      the chain length distribution of the polymers and on the total number of amino
      acid units.

PMID- 16791734
TI  - Model-free model elimination: a new step in the model-free dynamic analysis of
      NMR relaxation data.
AB  - Model-free analysis is a technique commonly used within the field of NMR
      spectroscopy to extract atomic resolution, interpretable dynamic information on
      multiple timescales from the R1, R2, and steady state NOE. Model-free approaches
      employ two disparate areas of data analysis, the discipline of mathematical
      optimisation, specifically the minimisation of a chi2 function, and the
      statistical field of model selection. By searching through a large number of
      model-free minimisations, which were setup using synthetic relaxation data
      whereby the true underlying dynamics is known, certain model-free models have
      been identified to, at times, fail. This has been characterised as either the
      internal correlation times, tau(e), tau(f), or tau(s), or the global correlation
      time parameter, local tau(m), heading towards infinity, the result being that the
      final parameter values are far from the true values. In a number of cases the
      minimised chi2 value of the failed model is significantly lower than that of all
      other models and, hence, will be the model which is chosen by model selection
      techniques. If these models are not removed prior to model selection the final
      model-free results could be far from the truth. By implementing a series of
      empirical rules involving inequalities these models can be specifically isolated
      and removed. Model-free analysis should therefore consist of three distinct
      steps: model-free minimisation, model-free model elimination, and finally model
      free model selection. Failure has also been identified to affect the individual
      Monte Carlo simulations used within error analysis. Each simulation involves an
      independent randomised relaxation data set and model-free minimisation, thus
      simulations suffer from exactly the same types of failure as model-free models.
      Therefore, to prevent these outliers from causing a significant overestimation of
      the errors the failed Monte Carlo simulations need to be culled prior to
      calculating the parameter standard deviations.

PMID- 16791735
TI  - Molecular conformations of a disaccharide investigated using NMR spectroscopy.
AB  - The molecular structure of alpha-L-Rhap-(1--> 2)-alpha-L-Rhap-OMe has been
      investigated using conformation sensitive NMR parameters: cross-relaxation rates,
      scalar 3J(CH) couplings and residual dipolar couplings obtained in a dilute
      liquid crystalline phase. The order matrices of the two sugar residues are
      different, which indicates that the molecule cannot exist in a single
      conformation. The conformational distribution function, P(phi, psi) related to
      the two glycosidic linkage torsion angles phi and psi was constructed using the
      APME method, valid in the low orientational order limit. The APME approach is
      based on the additive potential (AP) and maximum entropy (ME) models. The
      analyses of the trajectories generated in molecular dynamics and Langevin
      dynamics (LD) computer simulations gave support to the distribution functions
      constructed from the experimental NMR parameters. It is shown that at least two
      conformational regions are populated on the Ramachandran map and that these
      regions exhibit very different molecular order.

PMID- 16791736
TI  - Interference between cross-correlated relaxation and the measurement of scalar
      and dipolar couplings by Quantitative J.
AB  - The effects of cross-correlated relaxation in Quantitative J methods are
      analyzed. One-bond 1H-13C scalar and dipolar couplings of protein methine and
      methylene sites are obtained by monitoring proton and carbon magnetization in
      Quantitative J experiments. We find that scalar and dipolar couplings of the same
      pair of nuclei vary depending on the type of magnetization involved. These
      discrepancies can be as large as several Hz for methylene moieties. The
      contribution of dynamic frequency shifts, which are known to affect J couplings,
      is too small to explain the observed differences. We show that processes of
      magnetization transfer originated by cross-correlated relaxation are largely
      responsible for these discrepancies. We estimate the error transferred to
      methylene J values by cross-correlation interference, and show that is close to
      the experimentally observed one. Furthermore, this analysis indicates that cross
      correlated relaxation effects under isotropic and anisotropic media differ,
      indicating that errors are not cancelled in residual dipolar coupling
      measurements.

PMID- 16791737
TI  - iDC: A comprehensive toolkit for the analysis of residual dipolar couplings for
      macromolecular structure determination.
AB  - Measurement of residual dipolar couplings (RDCs) has become an important method
      for the determination and validation of protein or nucleic acid structures by
      NMRf spectroscopy. A number of toolkits have been devised for the handling of RDC
      data which run in the Linux/Unix operating environment and require specifically
      formatted input files. The outputs from these programs, while informative,
      require format modification prior to the incorporation of this data into commonly
      used personal computer programs for manuscript preparation. To bridge the gap
      between analysis and publication, an easy-to-use, comprehensive toolkit for RDC
      analysis has been created, iDC. iDC is written for the WaveMetrics Igor Pro
      mathematics program, a widely used graphing and data analysis software program
      that runs on both Windows PC and Mac OS X computers. Experimental RDC values can
      be loaded into iDC using simple data formats accessible to Igor's tabular data
      function. The program can perform most useful RDC analyses, including alignment
      tensor estimation from a histogram of RDC occurrence versus values and order
      tensor analysis by singular value decomposition (SVD). SVD analysis can be
      performed on an entire structure family at once, a feature missing in other
      applications of this kind. iDC can also import from and export to several
      different commonly used programs for the analysis of RDC data (DC, PALES, REDCAT)
      and can prepare formatted files for RDC-based refinement of macromolecular
      structures using XPLOR-NIH, CNS and ARIA. The graphical user interface provides
      an easy-to-use I/O for data, structures and formatted outputs.

PMID- 16791738
TI  - Automated resonance assignment of proteins: 6D APSY-NMR.
AB  - The 6-dimensional (6D) APSY-seq-HNCOCANH NMR experiment correlates two
      sequentially neighboring amide moieties in proteins via the C' and Calpha nuclei,
      with efficient suppression of the back transfer from Calpha to the originating
      amide moiety. The automatic analysis of two-dimensional (2D) projections of this
      6D experiment with the use of GAPRO (Hiller et al., 2005) provides a high
      precision 6D peak list, which permits automated sequential assignments of
      proteins with the assignment software GARANT (Bartels et al., 1997). The
      procedure was applied to two proteins, the 63-residue 434-repressor(1-63) and the
      115-residue TM1290. For both proteins, complete sequential assignments for all
      NMR-observable backbone resonances were obtained, and the polypeptide segments
      thus identified could be unambiguously located in the amino acid sequence. These
      results demonstrate that APSY-NMR spectroscopy in combination with a suitable
      assignment algorithm can provide fully automated sequence-specific backbone
      assignments of small proteins.

PMID- 16791739
TI  - Chemically accurate protein structures: validation of protein NMR structures by
      comparison of measured and predicted pKa values.
AB  - A new method is presented for evaluating the quality of protein structures
      obtained by NMR. This method exploits the dependence between measurable chemical
      properties of a protein, namely pKa values of acidic residues, and protein
      structure. The accurate and fast empirical computational method employed by the
      PROPKA program ( http://www.propka.chem.uiowa.edu) allows the user to test the
      ability of a given structure to reproduce known pKa values, which in turn can be
      used as a criterion for the selection of more accurate structures. We demonstrate
      the feasibility of this novel idea for a series of proteins for which both NMR
      and X-ray structures, as well as pKa values of all ionizable residues, have been
      determined. For the 17 NMR ensembles used in this study, this criterion is shown
      effective in the elimination of a large number of NMR structure ensemble members.

PMID- 16791740
TI  - Heteronuclear multidimensional NMR and homology modelling studies of the C
      terminal nucleotide-binding domain of the human mitochondrial ABC transporter
      ABCB6.
AB  - Human ATP-binding cassette, sub-family B, member 6 (ABCB6) is a mitochondrial ABC
      transporter, and presumably contributes to iron homeostasis. Aimed at
      understanding the structural basis for the conformational changes accompanying
      the substrate-transportation cycle, we have studied the C-terminal nucleotide
      binding domain of ABCB6 (ABCB6-C) in both the nucleotide-free and ADP-bound
      states by heteronuclear multidimensional NMR and homology modelling. A non-linear
      sampling scheme was utilised for indirectly acquired 13C and 15N dimensions of
      all 3D triple-resonance NMR experiments, in order to overcome the instability and
      the low solubility of ABCB6-C. The backbone resonances for approximately 25% of
      non-proline residues, which are mostly distributed around the functionally
      important loops and in the Helical domain, were not observed for nucleotide-free
      form of ABCB6-C. From the pH, temperature and magnetic field strength
      dependencies of the resonance intensities, we concluded that this incompleteness
      in the assignments is mainly due to the exchange between multiple conformations
      at an intermediate rate on the NMR timescale. These localised conformational
      dynamics remained in ADP-bound ABCB6-C except for the loops responsible for
      adenine base and alpha/beta-phosphate binding. These results revealed that the
      localised dynamic cooperativity, which was recently proposed for a prokaryotic
      ABC MJ1267, also exists in a higher eukaryotic ABC, and is presumably shared by
      all members of the ABC family. Since the Helical domain is the putative interface
      to the transmembrane domain, this cooperativity may explain the coupled functions
      between domains in the substrate-transportation cycle.

PMID- 16791741
TI  - Second Kunitz-type protease inhibitor domain of the human WFIKKN1 protein.

PMID- 16791742
TI  - Measuring health status and decline in at-risk seniors residing in the community
      using the Health Utilities Index Mark 2.
AB  - PURPOSE: The purpose of this study was to assess the responsiveness of one
      measure of HRQL, the HUI Mark 2 (HUI2), to changes in health status over time in
      an older community-based population. METHODS: The sample consisted of 192
      individuals age 65 and over residing in their homes and receiving health and
      support services in Calgary, Canada. Subjects received three assessments at 6
      month intervals using the HUI2, to measure health-related quality of life (HRQL),
      and the Minimum Data Set for Home Care (MDS-HC) for demographic and health status
      information. Change scores were calculated as the difference between scores at
      the second and third assessments. The relationship between the HUI2 and other
      measures of health status were examined using t-tests and ANOVA. Associations
      between the magnitude of decline in HUI2 and declines on other measures were
      examined using multiple linear regression. RESULTS: Lower HUI2 scores were
      significantly associated with the presence of depressive symptoms, impairment in
      activities of daily living (ADL), and clinical instability at baseline. Over 6
      months of follow-up, HUI2 decline was associated with worsening depressive
      symptoms, increase in the number of chronic conditions, and age 85 and over.
      CONCLUSION: The HUI2 measure of HRQL in older persons at risk for
      institutionalization appears to reflect health status at a point in time and to
      be responsive to changes in health status over time.

PMID- 16791743
TI  - The association between symptom burdens and utility in Chinese cancer patients.
AB  - OBJECTIVES: This study explored the relationship between the M. D. Anderson
      Symptom Inventory (MDASI), an instrument measuring the severity of symptoms
      common to patients with cancer, and utility derived from the SF-36. METHODS:
      Cancer patients from Tianjin Cancer Hospital in China (n = 249) completed a
      demographic questionnaire and Chinese versions of the MDASI and SF-36. Using a
      published algorithm converting SF-36 scores to standard gamble (SG) utilities, we
      examined the association between utility and individual symptoms using Spearman's
      rank correlation, and explored the association between utility and aggregate
      symptom scores through multivariate regression analyses. RESULTS: The mean SG
      utility was 0.81 (SD = 0.11); utilities were significantly but moderately
      correlated with the majority of symptoms, especially those of distress, sadness,
      fatigue, and pain. Regression models showed a significantly negative association
      between the total symptom score and the utility. After controlling for
      sociodemographics, cancer stage and performance status, a significantly negative
      association between the total symptom scores and utility was found in the
      multivariate analyses. We also found the total number of severe symptoms to be a
      stronger predictor of "disutility." CONCLUSIONS: Symptom measures were
      significantly albeit moderately associated with utility derived from the SF-36
      scores, suggesting that a full study with rigorously collected utilities is worth
      exploring.

PMID- 16791744
TI  - Influence of dopamine deficiency in early Parkinson's disease on the slow
      stimulation multifocal-ERG.
AB  - PURPOSE: In animal studies intravitreal injection of tetrodotoxin (TTX) results
      in mfERG waveform changes similar to those observed in glaucoma. As TTX blocks
      amacrine as well as ganglion cells, there is still a question regarding the
      underlying cell population responsible for these changes in waveform. In an
      attempt to assess the contribution of the amacrine cells to these changes, a
      mfERG was obtained from patients with Parkinson's disease as some amacrine cells
      are mediated by dopamine, a substance lacking in Parkinson's. METHODS: Eight
      patients with early Parkinson's disease underwent ophthalmologic examination,
      testing of contrast sensitivity and electrophysiological examination according to
      ISCEV standard at least 12 h following their last medication with Dopamine. A
      slow stimulation mfERG was obtained with a stimulus base interval of 53.3 ms and
      with a stimulus base interval of 106.6 ms. During MF-ERG recordings 103 hexagons
      stimulated the central 50 deg of the retina simultaneously and independently (m
      sequence 2(13), L(max): 200 cd/m(2), approximately 100% contrast). RESULTS:
      Contrast sensitivity and ISCEV standard electrophysiological testing was
      unremarkable. When the mfERG was analyzed, only four patients had an adequate
      signal-to-noise ratio to allow further data analysis - one of whom was diagnosed
      with a multi system atrophy in retrospect. The first order response component was
      analyzed at a filter setting of 10-300 Hz and at 100-300 Hz (OPs) and compared to
      mfERGs of a control group. On average, in patients, the amplitude of N1P1 was
      slightly lower in the central and nasal response averages. When the three OPs at
      a latency of 72-89 ms were analyzed in the 53.3 ms base interval recording, the
      most marked difference in amplitude was observed in the superior nasal response
      average of the first OP. Here a mean amplitude of 1.3 nV/deg(2) in patients
      compared to a mean amplitude of 1.9 nV/deg(2) in the control group (P: 0.08).
      DISCUSSION: In contrast to our previous findings in NTG, there was a consistent
      presence of three OPs. Under the stimulus conditions applied, we did not find an
      influence of dopaminergic amacrine cells on the mfERG in our patients with
      moderate stages of Parkinsion's. The difficulties in obtaining an adequate signal
      to noise ratio due to e.g. muscle artifacts even in Parkinson patients of
      moderate disease stages render a success of mfERG recording in patients with more
      advanced stages unlikely. The question of the influence of dopaminergic amacrine
      cells on the mfERG could possibly be addressed using MPDT in animal research.

PMID- 16791745
TI  - Assessing primary and bacterial production rates in biofilms on pebbles in Ishite
      stream, Japan.
AB  - Various measurements of microbial productivity in streambed pebble biofilms were
      analyzed almost monthly for 1 year to quantify the importance of primary
      production as an autochthonous source of organic matter utilized to support
      heterotrophic bacterial production in the dynamic food web within this natural
      microbial habitat. Bacterial density varied from 0.3x10(8) to 1.4x10(8) cells cm
      2, and chlorophyll a concentration ranged from 0.7 to 25.9 microg cm-2, with no
      coupled oscillation between seasonal changes in these two parameters. In bottle
      incubation experiments, the instantaneous bacterial growth rate of bacteria was
      significantly correlated with their production rate [measured by frequency of
      dividing cells (FDC)] as follows: ln mu=0.138FDC-3.003 (n=15, r2=0.445, p<0.001).
      FDC values in the pebble biofilms increased with fluctuations during the study
      period, ranging from 3.6% to 9.2%. Bacterial production rates largely fluctuated
      between 0.15 to 0.92 microg C cm-2 h-1, and its seasonal pattern was similar to
      that of bacterial density. Net primary production measured between May 2002 to
      November 2002 attained minimum level (0.5 microg C cm-2 h-1) in June and maximum
      level (1.9 microg C cm-2 h-1) in August. Percentages of bacterial production to
      net primary production ranged between 21% and 120%. Because this ratio extends
      both below and above 100% for these parameters, it is likely that both
      autochthonous and allochthonous supplies of organic matter are important for
      production of bacteria in the pebble biofilms that develop in rapidly flowing
      fresh water streams.

PMID- 16791746
TI  - In vivo phage display selection yields atherosclerotic plaque targeted peptides
      for imaging.
AB  - PURPOSE: Atherosclerosis is a leading cause of morbidity and mortality in the
      Western world, yet specific imaging agents to detect and map inflammatory plaques
      are still lacking. PROCEDURES: We used in vivo phage display to interrogate early
      atherosclerotic lesions present in ApoE-/- mice with the goal of identifying
      plaque-associated endothelial cell internalized affinity ligands. RESULTS: We
      identified 30 phage families with some of these families exhibiting homology to
      known atherosclerotic proteins, namely, leukemia inhibitory factor, transferrin,
      and VLA-4. VLA-4 homologous peptides [termed vascular cellular adhesion molecule
      1 (VCAM-1) internalizing peptide-28 (VINP28)] bound to and were internalized by
      VCAM-1-expressing cells and were inhibited by soluble VCAM-1. In addition, a
      VINP28 modified multimodal nanoparticle showed high affinity for endothelial
      cells expressing VCAM-1 but low affinity for macrophages or smooth muscle cells.
      CONCLUSION: The identified peptides represent a set of probes to interrogate the
      cell surface repertoire and potentially allow early detection of atherosclerosis.

PMID- 16791747
TI  - Renal oncocytoma on 1-11C acetate positron emission tomography: Case report and
      literature review.
AB  - Renal oncocytomas are uncommon tumors of the renal collecting duct. Although
      generally benign, these tumors pose a diagnostic and therapeutic dilemma in that
      they can not be differentiated noninvasively from renal cell carcinomas. We
      report a 67-year-old man who underwent a clinical 1-11C acetate positron emission
      tomography (PET) scan for evaluation of possible metastatic prostate carcinoma.
      The study demonstrated a nodule at the inferior pole of the right kidney with
      more uptake than the remainder of the kidney. Correlation was made with MRI,
      which demonstrated that the nodule was solid, and enhanced after contrast agent
      administration. Upon resection, this nodule was determined to be an oncocytoma.
      To our knowledge, this marks the first report of the 1-11C acetate PET scan
      appearance of a renal oncocytoma Possible mechanisms for increased uptake include
      dysfunctional, but up-regulated oxidative phosphorylation or uptake through lipid
      biosynthesis pathways.

PMID- 16791748
TI  - Evaluation of firefly luciferase bioluminescence mediated photodynamic toxicity
      in cancer cells.
AB  - PURPOSE: This work investigated whether fLuc-catalyzed oxidation of D-luciferin
      generates sufficient light to induce photodynamic toxicity in cancer cells.
      PROCEDURES: Light emission was assessed via cooled CCD (charge-coupled device)
      camera. Parental and fLuc expressing cancer cells were exposed to subtoxic
      concentrations of photosensitizers (Rose Bengal or hypericin) and D-luciferin,
      sunlight, or lamplight. Toxicity was assessed by MTT assay. RESULTS: fLuc
      expressing cells emitted up to 500-fold higher levels of photons than parental
      cell lines. Although exposure to photosensitizer and sunlight reduced survival of
      various cell lines, survival of fLuc expressing cells incubated with
      photosensitizer and D-luciferin, or photosensitizer and lamplight, did not differ
      significantly from parental or untreated cells. CONCLUSIONS: Contesting recent
      reports, fLuc bioluminescence does not generate sufficient photons to induce Rose
      Bengal or hypericin photodynamic toxicity in a range of malignant and
      nonmalignant cell lines, and is not suitable as a generalizable approach to
      antineoplastic therapy.

PMID- 16791749
TI  - Near-infrared fluorescence imaging of tumor integrin alpha v beta 3 expression
      with Cy7-labeled RGD multimers.
AB  - PURPOSE: Cell adhesion molecule integrin alpha v beta 3 is an excellent target
      for tumor interventions because of its unique expression on the surface of
      several types of solid tumor cells and on almost all sprouting tumor
      vasculatures. Here, we describe the development of near-infrared (NIR)
      fluorochrome Cy7-labeled RGD peptides for tumor integrin targeting. PROCEDURES:
      Mono-, di-, and tetrameric RGD peptides were synthesized and conjugated with Cy7.
      The integrin specificity of these fluorescent probes was tested in vitro for
      receptor binding assay and fluorescence microscopy and in vivo for subcutaneous
      U87MG tumor targeting. RESULTS: The tetrameric RGD peptide probe with the highest
      integrin affinity showed the highest tumor activity accumulation and strongest
      tumor-to-normal tissue contrast. This uptake is integrin-specific as the signal
      accumulated in the tumor can be effectively blocked by unconjugated RGD peptide
      antagonist of integrin alpha v beta 3. CONCLUSIONS: Noninvasive NIR fluorescence
      imaging is able to detect and semiquantify tumor integrin expression based upon
      the highly potent tetrameric RGD peptide probe.

PMID- 16791750
TI  - The effect of insulin on the intracellular distribution of 14(R,S)-[18F]Fluoro-6
      thia-heptadecanoic acid in rats.
AB  - PURPOSE: The aim of this study was to determine the effect of hyperinsulinemia on
      myocardial and hepatic distribution and metabolism of 14(R,S)-[18F]fluoro-6-thia
      heptadecanoic acid ([18F]FTHA). PROCEDURES: Mitochondrial retention and
      intracellular lipid incorporation of [18F]FTHA were compared to that of [14C]-2
      bromopalmitate or [14C]palmitate during hyperinsulinemic clamp vs. saline
      infusion in male Wistar rats. RESULTS: Mitochondrial 18F activity was increased
      in the heart (1.7 +/- 0.4 vs. 0.5 +/- 0.1% ID/g, P < 0.05), whereas it was
      reduced in the liver (1.1 +/- 0.3 vs. 1.8 +/- 0.4% ID/g, P < 0.05) during insulin
      vs. saline infusion, respectively. Mitochondrial [14C]-2-bromopalmitate activity
      was affected by insulin in a similar way in both tissues. The fractional
      esterification of [18F]FTHA into triglycerides was impaired compared to
      [14C]palmitate in both tissues, and [18F]FTHA was insensitive to the shift of
      esterification of fatty acids into complex lipids in response to insulin.
      CONCLUSIONS: [18F]FTHA is sensitive to insulin-induced modifications of free
      fatty acid oxidative metabolism in rats but is insensitive to changes in
      nonoxidative fatty acid metabolism.

PMID- 16791754
TI  - Neurological disorders in the intensive care unit.
AB  - Neurological problems are common among critically ill patients; they often signal
      that other organs are failing, but are themselves important causes of morbidity
      and mortality. Cognitive function may suffer as a consequence of septic
      encephalopathy, the pathophysiology of which is poorly understood; however, the
      affected patients usually return to their baseline when sepsis resolves. Seizures
      and cerebrovascular disorders are also common in the intensive care unit.
      Neuromuscular complications are important causes of failure to wean from
      mechanical ventilation and lead to substantial long-term morbidity.

PMID- 16791751
TI  - Impact of scar on water-perfusable tissue index in chronic ischemic heart
      disease: Evaluation with PET and contrast-enhanced MRI.
AB  - BACKGROUND: The water-perfusable tissue index (PTI) is assumed to differentiate
      viable myocardium from scar tissue, but histological comparisons in humans are
      lacking. The present study compares PTI with delayed contrast-enhanced magnetic
      resonance imaging (DCE-MRI), a validated marker of fibrotic tissue, in patients
      with ischemic left ventricular (LV) dysfunction. In addition, the optimal PTI
      threshold for detection of myocardial viability was defined when DCE-MRI was
      taken as a reference. MATERIALS: Twenty patients with ischemic LV dysfunction
      were studied with positron emission tomography, using oxygen-15-labeled water and
      carbon monoxide as tracers, and DCE-MRI. RESULTS: Of the 200 analyzed segments,
      112 demonstrated DCE and were subsequently divided in three subgroups according
      to the severity of enhancement. PTI was 1.04 +/- 0.21 in control segments and
      gradually decreased with increasing extent of DCE to 0.77 +/- 0.31 for segments
      with transmural enhancement (p < 0.001). However, PTI progressively
      underestimated infarct size with increasing quantities of scar tissue (r = 0.61,
      p < 0.01). A PTI cutoff value of 0.89 yielded the best diagnostic accuracy for
      detection of myocardial viability with sensitivity and specificity values of 75
      and 77%, respectively. CONCLUSIONS: PTI is inversely related to the extent of
      scar tissue estimated by DCE-MRI in patients with chronic ischemic heart disease
      and LV dysfunction. However, with increasing quantities of scar tissue, PTI
      overestimates the extent of residual viable tissue. A PTI threshold of 0.89
      yields the best diagnostic accuracy for viability detection.

PMID- 16791755
TI  - Delirium and cognitive dysfunction in the intensive care unit.
AB  - Delirium remains a non recognized, but highly prevalent, form of organ
      dysfunction in the intensive care unit (ICU). Intensive care physicians have
      begun to benefit from elucidation of risk factors for delirium in the ICU, some
      of which are modifiable, whereas others are not. In the last 5 years, a new tool
      for use in detecting delirium among critically ill patients has been adapted,
      validated, and found objectively reliable for use at the bedside by
      nonpsychiatrists. Moreover, that tool-the Confusion Assessment Method for the
      Intensive Care Unit (CAM-ICU)-has enabled determination of the serious sequelae
      of delirium, including increased mortality, higher cost, longer length of
      hospital stay, failure of extubation, and burdensome long-term cognitive
      impairment. Although prevention and treatment options exist, little data guide
      current pharmacological approaches to delirium, and nonpharmacological approaches
      have yet to be fully adopted by ICUs. Ongoing trials will address some of these
      limitations, but large cohort studies within the ICU are needed to further
      clarify risk factors and to identify targets to modify the occurrence and course
      of delirium. Furthermore, consideration of a continuum may better elucidate the
      true magnitude of acute brain dysfunction in the ICU.

PMID- 16791756
TI  - Cardiac arrhythmias in the intensive care unit.
AB  - Cardiac arrhythmias are a common problem encountered in the intensive care unit
      (ICU) and represent a major source of morbidity. Arrhythmias are most likely to
      occur in patients with structural heart disease. The inciting factor for an
      arrhythmia in a given patient may be an insult such as hypoxia, infection,
      cardiac ischemia, catecholamine excess (endogenous or exogenous), or an
      electrolyte abnormality. Management includes correction of these imbalances as
      well as medical therapy directed at the arrhythmia itself. The physiological
      impact of arrhythmias depends on ventricular response rate and duration, and the
      impact of a given arrhythmia in a given situation depends on the patient's
      cardiac physiology and function. Similarly, urgency and type of treatment are
      determined by the physiological impact of the arrhythmia as well as by underlying
      cardiac status. The purpose of this review is to provide an update regarding
      current concepts of diagnosis and acute management of arrhythmias in the ICU. A
      systematic approach to diagnosis and evaluation will be presented, followed by
      consideration of specific arrhythmias.

PMID- 16791757
TI  - Evaluation and management of shock.
AB  - Shock is one of the most frequent situations encountered in the intensive care
      unit (ICU). Important new concepts have emerged for shock management in recent
      years. The concept of early goal-directed therapy has evolved from the basic
      management concepts for septic shock delivered in a structured fashion. Numerous
      cardiovascular techniques, methods, and strategies have been developed as novel
      alternatives to the use of the pulmonary artery catheter. Among these techniques,
      echocardiography, esophageal Doppler, and arterial pulse contour analysis show
      great promise. Prediction of responsiveness to fluid administration is a key
      component of the management of shock, as is assessing cardiovascular performance.
      The intensive care physician has several options to evaluate and treat shock.
      Further research should yield additional important advances.

PMID- 16791758
TI  - Intensive management of hepatic failure.
AB  - A substantial number of patients with liver failure are admitted to the intensive
      care unit; thus a thorough understanding of the prevention and treatment of
      complications in such patients is imperative. The management of liver failure is
      demanding and often involves the combined efforts of many specialists. Critically
      ill patients with hepatic failure encompass a broad spectrum of disease, ranging
      from acute liver failure in a patient with no prior history of liver disease, to
      acute or chronic liver failure. The initial assessment and management of acute
      liver failure are reviewed with an emphasis on the prevention and treatment of
      brain edema in the pretransplant setting. The current treatment of complications
      resulting from decompensated chronic liver disease such as portal hypertensive
      bleeding; infection, renal failure, and hepatic encephalopathy are then
      discussed.

PMID- 16791759
TI  - Acute renal failure in the intensive care unit.
AB  - Acute renal failure (ARF) is a common complication in critically ill patients,
      with ARF requiring renal replacement therapy (RRT) developing in approximately 5
      to 10% of intensive care unit (ICU) patients. Epidemiological studies have
      demonstrated that ARF is an independent risk factor for mortality. Interventions
      to prevent the development of ARF are currently limited to a small number of
      settings, primarily radiocontrast nephropathy and rhabdomyolysis. There are no
      effective pharmacological agents for the treatment of established ARF. Renal
      replacement therapy remains the primary treatment for patients with severe ARF;
      however, the data guiding selection of modality of RRT and the optimal timing of
      initiation and dose of therapy are inconclusive. This review focuses on the
      epidemiology and diagnostic approach to ARF in the ICU and summarizes our current
      understanding of therapeutic approaches including RRT.

PMID- 16791760
TI  - Stress hyperglycemia and adrenal insufficiency in the critically ill.
AB  - Critical illness evoked by trauma, extensive surgery, or severe medical illnesses
      is the ultimate example of acute severe physical stress. The endocrine response
      in a critically injured and stressed patient is varied and complex. Although the
      acute and chronic phases of critical illness are characterized by distinct
      endocrine responses, the diagnosis of these disorders is controversial. The
      inability to define the endocrine change as either adaptation or pathology
      renders the issue of treatment even more controversial. In addition, patients may
      have preexisting endocrine diseases, either previously diagnosed or unknown, and
      hence endocrine evaluation in a critically ill patient poses a major challenge to
      the health care provider. This review provides a novel insight into the dynamic
      endocrine alterations that occur during evolution of stress hyperglycemia and
      adrenal insufficiency in the critically ill patient and the available evidence
      for the therapy of these disorders.

PMID- 16791761
TI  - Hematologic disorders in critically ill patients.
AB  - Hematologic disorders are frequently encountered in the intensive care unit.
      Thrombocytopenia, often defined as a platelet count below 100,000/microL, is
      common in critically ill patients and may be associated with adverse outcomes. A
      systematic evaluation of clinical and laboratory findings is necessary to
      ascertain the cause of the thrombocytopenia and to determine the correct therapy.
      Recognition of heparin-induced thrombocytopenia (HIT) is particularly important,
      given the risk of thrombosis associated with this condition. Prompt cessation of
      all heparin products is required, and anticoagulation with a direct thrombin
      inhibitor is recommended if HIT is strongly suspected. Coagulopathies are also
      common in the critically ill, and are often due to vitamin K deficiency or
      disseminated intravascular coagulation (DIC). A careful history and
      interpretation of clotting studies are useful in defining the coagulation defect.
      Advances in understanding the pathogenesis of DIC have generated new treatment
      approaches, such as the use of recombinant activated protein C. Recombinant
      factor VIIa (rFVIIa) is a novel drug approved for use in patients with congenital
      hemophilia and inhibitors. Although its use as a hemostatic agent is currently
      being evaluated in several off-label scenarios, including trauma, intracerebral
      hemorrhage, and liver disease, there are limited data to guide therapy in these
      conditions.

PMID- 16791762
TI  - Major complications following hematopoietic stem cell transplantation.
AB  - Tens of thousands of patients undergo hematopoietic stem cell transplantation
      (HSCT) annually, 15 to 40% of whom are admitted to the intensive care unit.
      Pulmonary complications are the most life threatening conditions that develop in
      HSCT recipients. Both infectious and noninfectious complications occur more
      frequently in allogeneic HSCT. The management of HSCT recipients requires
      knowledge of their immune status, appropriate diagnostic evaluation, and early
      treatment. During the pre-engraftment phase (0 to 30 days after transplant), the
      most prevalent pathogens causing infection are bacteria and Candida species and,
      if the neutropenia persists, Aspergillus species. The early post-engraftment
      phase (30 to 100 days) is characterized by cytomegalovirus (CMV), Pneumocystis
      jiroveci, and Aspergillus infections. During the late posttransplant phase (> 100
      days), allogeneic HSCT recipients are at risk for CMV, community-acquired
      respiratory virus, and encapsulated bacterial infections. Antigen and polymerase
      chain reaction assays are important for the diagnosis of CMV and Aspergillus
      infections. Diffuse alveolar hemorrhage (DAH) and peri-engraftment respiratory
      distress syndrome occur in both allogeneic and autologous HSCT recipients,
      usually during the first 30 days. Bronchiolitis obliterans occurs exclusively in
      allogeneic HSCT recipients with graft versus host disease. Idiopathic pneumonia
      syndrome occurs at any time following transplant. Bronchoscopy is usually helpful
      for the diagnosis of the infectious pulmonary complications and DAH.

PMID- 16791763
TI  - Infection control and the prevention of nosocomial infections in the intensive
      care unit.
AB  - Nosocomial infections continue to be significant causes of morbidity, mortality,
      and added costs in the health care setting. Half of all life-threatening
      nosocomial bloodstream infections and pneumonias occur in intensive care units
      (ICUs), despite ICUs representing only 15 to 20% of all hospital beds. Thus an
      efficient focus for prevention and control of life-threatening health care
      associated infections should be in ICUs. Further, growing antibiotic resistance
      complicates the therapy of serious infections. Meticulous infection control
      practice with continued attention to hand hygiene is of paramount importance.
      Strict adherence to evidence-based catheter insertion and maintenance policies
      reduces nosocomial bloodstream infections. Evidence-based prevention strategies
      for ventilator-associated pneumonia, including management of respiratory
      equipment according to published guidelines and maintaining backrest elevation at
      30 to 45 degrees, are effective. For greatest risk reduction, multifaceted
      programs ensuring maximal adherence with evidence-based infection control
      guidelines are needed.

PMID- 16791766
TI  - [The short-term ventilation tube].

PMID- 16791767
TI  - [Peripheral facial palsy as the first symptom of a metastatic bronchogenic
      carcinoma].
AB  - BACKGROUND: We present a case of a facial palsy as the initial symptom of a
      bronchogenic carcinoma. METHODS: Case-report. A 56-year-old patient presented
      with a peripheral facial palsy. The clinical picture as well as the temporal bone
      CT were without pathological findings. A 10-day rheologic therapy as well as anti
      viral medication were not successful. Five days after rheological therapy had
      been completed, the patient presented a swelling of the neck. In the computer
      tomography we found a bilateral thrombosis of the internal jugular vein. In
      addition, the clinical picture of a left-sided glossopharyngeal palsy appeared.
      The following thorax CT as well as the diagnostic extirpation of an enlarged
      cervical lymph node lead to the diagnosis of a metastasized smallcell neuro
      endocrine bronchogenic carcinoma with a compression of the right primary bronchus
      and the vena cava superior as well as an upper inflow congestion. In the cMRT we
      furthermore found a metastasis in the area of the foramen stylomastoideum. The
      patient underwent emergency radiation and chemotherapy. RESULTS: According to the
      present findings, this metastasis lead to the facial palsy as the initial symptom
      of the bronchogenic carcinoma. CONCLUSION: Therefore, therapy resistant facial
      palsy should be further diagnosed in detail, especially examined by imaging
      procedures.

PMID- 16791769
TI  - Frequency and timing of leaf removal affect growth and podophyllotoxin content of
      Podophyllum peltatum in full sun.
AB  - Podophyllotoxin is a pharmaceutical compound found in leaves and rhizomes of
      American mayapple (P. peltatum L.), a species being investigated as an
      alternative to that of the Indian mayapple (P. emodi). Leaves alone can serve as
      a renewable source of podophyllotoxin (and other lignans) leaving rhizomes
      undisturbed to produce leaf biomass in subsequent years. It is not known,
      however, how frequently or severely plants can be defoliated without adversely
      affecting future plant growth, lignan content, or podophyllotoxin yield (g.m(
      2)). This study compared harvest strategies that were mild to severe in frequency
      and timing of leaf removal. A wild population in full sun was subjected to leaf
      removal treatments of varying frequency (every year, every 2nd or 3rd year) and
      timing (early or late). Control plots not previously harvested were included
      every year. Plots were 1.0 m2 and established during spring of 2001. Duration of
      the study was four years. P. peltatum plants did not tolerate the most severe
      harvest treatment: annual harvest frequency in combination with early harvest
      time. Early annual harvests reduced total leaf dry mass and total leaf area in a
      consistent and linear manner. In contrast, plants tolerated annual harvests when
      conducted late in the growing season and tolerated early harvests when conducted
      every 2nd or 3rd year. The number of sexual shoots was reduced to zero by early
      annual harvests. Podophyllotoxin content was 2.7 to 6.5 times greater in leaves
      harvested early compared to those harvested late, though content was
      significantly greater in only two out of four years. In conclusion, we can
      recommend leaf removal every year from well-established P. peltatum populations
      grown in full sun if harvests are conducted late in the growing season. This
      harvest strategy ensures maximum podophyllotoxin yield without jeopardizing
      future leaf biomass yield. Leaves harvested early appear to have greater
      podophyllotoxin content, but we discourage early harvest every year. Instead, our
      results indicate that leaves can be harvested early every other year without
      reducing long-term performance of P. peltatum populations.

PMID- 16791768
TI  - [New substances in the therapy of head and neck cancer].
AB  - During the last 3 years the FDA approved numerous innovative drugs for cancer
      therapy. Drugs relevant to the otolaryngologist are presented and discussed.
      These new therapeutic tools may play a future part also in the therapy of head
      and neck cancer.

PMID- 16791770
TI  - Authentication of medicinal plant botanical identity by amplified fragmented
      length polymorphism dominant DNA marker: inferences from the Plectranthus genus.
AB  - In Brazil, Plectranthus species are known as "boldo" and have been used in
      popular medicine for analgesic and dyspeptic purposes. Plectranthus need to be
      well identified in order to be used as commercially genuine medicinal plants.
      Here we describe AFLP DNA patterns able to distinguish among different
      Pectranthus species. The genetic variability of P. grandis Cramer, P. barbatus
      Andr. and P. ornatus Codd was analyzed with two sets of AFLP primers allowing
      detection of 241 loci. A total of 22 monomorphic loci were identified in P.
      barbatus, 15 in P. grandis and 30 in P. ornatus. Among these, 5 loci were
      informative and species-specific to P. barbatus, 3 to P. grandis and 2 loci were
      unique to P. ornatus. The AFLP pattern analyzed by different clustering methods
      assembled individuals according to their species. So far, AFLP represents a
      genuine and strong method to certify medicinal plant materials.

PMID- 16791774
TI  - Evaluation and diagnosis of psychogenic disorders in neurological patients.
AB  - Patients with psychogenic neurological symptoms present a diagnostic challenge.
      There are certain elements in a history that are indicative of a psychogenic
      condition. These include sudden onset of symptoms, highly emotional events at the
      time of symptom onset, paroxysmal nature of symptoms, and migrating or changing
      complaints. Likewise, some findings on examination are more often seen in
      psychogenic cases than in organic disorders. Multiple symptoms that do not
      correspond to any identifiable neuroanatomical abnormality, distractibility,
      entrainment, and false weakness or sensory complaints, are all possible clues
      that a condition is emotional rather than organic. However, none of these
      features is an absolute indication of psychogenicity and each must be taken in
      the context of the complete clinical picture.

PMID- 16791775
TI  - Psychogenic movement disorders.
AB  - All varieties of movement disorders may be mimicked by a psychogenic disorder,
      most commonly tremor, dystonia, and myoclonus. Approximately 3% of patients seen
      in specialty clinics have a psychogenic movement disorder (PMD). The diagnosis of
      a PMD depends on not just ruling out an organic movement disorder, but moreover,
      recognizing features from the history and examination that are inconsistent or
      incongruous with an organic movement disorder. Most PMDs represent a conversion
      disorder, sometimes as part of a somatoform disorder; less common diagnoses
      include a factitious disorder or malingering. Co-morbid psychiatric illness is
      prevalent in patients with PMD including depression, anxiety, and personality
      disorders. Many PMDs remain chronic, but a multidisciplinary approach centering
      on psychiatric intervention can be successful. A shorter duration of symptoms and
      a co-existent treatable psychiatric disorder portend a better prognosis, whereas
      compensation and pending litigation are associated with a poorer prognosis.

PMID- 16791776
TI  - Functional weakness and sensory loss.
AB  - Functional weakness and sensory loss are common clinical problems with variable
      presentations. Functional weakness commonly presents as weakness of an entire
      limb, paraparesis, or hemiparesis, with observable or demonstrable
      inconsistencies and nonanatomic accompaniments. Documentation of limb movements
      during sleep, the arm drop test, the Babinski thigh-trunk test, Hoover tests, the
      Sonoo abductor test, and various dynamometer tests can provide useful bedside
      diagnostic information on functional weakness. Functional sensory loss typically
      affects all sensory modalities, either in a hemisensory distribution or affecting
      an entire limb. Although often inconsistent over serial examinations with
      nonanatomic features, many clinical findings reported to be helpful in diagnosing
      functional sensory loss are neither sensitive nor specific for functional sensory
      loss. The yes-no test, Bowlus-Currier test, and forced-choice tests can provide
      useful bedside diagnostic information on functional sensory loss. Clinicians must
      be prepared to make more than one diagnosis in some cases, including an organic
      neurological diagnosis and a diagnosis of functional overlay. Recent studies have
      reported relatively low rates (<5%) of misdiagnosis of functional weakness or
      sensory loss as indicated by subsequent diagnosis of neurological or psychiatric
      conditions that explained the presenting symptoms. Most neurologists find such
      patients more difficult to help than patients with organic disease. Management
      focuses on supportive psychotherapy and behavioral management, exploration of
      social and psychological issues, treatment of comorbid depression or anxiety, and
      facilitation of development of more appropriate and constructive coping methods.
      Many patients with functional weakness, and to a somewhat lesser extent
      functional sensory loss, have persisting or relapsing-remitting somatic symptoms
      and persistently impaired social/interpersonal, occupational, and psychological
      functioning.

PMID- 16791777
TI  - Neuro-ophthalmologic manifestations of psychogenic disease.
AB  - From a neuro-ophthalmologic standpoint, five areas may be affected by psychogenic
      disease: (1) vision, including visual acuity and visual field; (2) ocular
      motility and alignment; (3) pupillary size and reactivity; (4) eyelid position
      and function; and (5) corneal and facial sensation. The physician faced with a
      patient complaining of decreased vision or some other disturbance related to the
      afferent or efferent visual systems for which there is no apparent biologic
      explanation has three responsibilities. First, the physician must ascertain that
      an organic disorder is not present. Second, the physician should induce the
      patient to see or do something that would not be possible if the condition were
      organic in nature. Finally, the physician should attempt to determine whether the
      patient has an underlying psychiatric disease or is experiencing psychosocial
      stress. In this article, manifestations of psychogenic disease as they pertain to
      vision are considered, and, where appropriate, the various methods used to
      diagnose and treat these phenomena are discussed.

PMID- 16791778
TI  - Nonorganic hearing loss.
AB  - Nonorganic hearing loss is a decrease in hearing that is unexplained by anatomic
      or physiologic abnormalities, or both. The term is synonymous with functional
      hearing loss and pseudohypacusis. The demographics and potential etiologies of
      nonorganic hearing loss are described. History and physical findings that
      indicate a functional hearing loss are also discussed. A review of the anatomy
      and physiology of the auditory system is provided as a background for the
      discussed objective tests of hearing thresholds. Finally, conditions that may
      mimic functional hearing loss are described in detail.

PMID- 16791779
TI  - Functional ("psychogenic") amnesia.
AB  - Patients who present with severely impaired memory functioning without a
      discernable neurological cause typically have experienced one or more severely
      stressful life events. These patients, who are described as having "psychogenic"
      or "dissociative" amnesia, typically differ from patients with the neurologic
      amnestic syndrome in that memory for their personal life histories is much more
      severely affected than is their ability to learn and retain new information; that
      is, they have isolated retrograde amnesia. Recent cognitive and brain imaging
      research has begun to reveal some of the cerebral mechanisms underlying
      functional amnesia, but this disorder remains best conceptualized as a relatively
      rare form of illness-simulating behavior rather than a disease.
      Neuropsychological assessment is often useful in revealing the circumscribed
      nature of the patient's performance deficits, the spared functions that can be
      brought to bear in rehabilitation, and the emotional disorders requiring
      psychiatric treatment. Controlled treatment trials are nonexistent, but case
      reports suggest that supportive psychotherapy, systematic relaxation training,
      hypnosis, and sedative/anxiolytic medications are useful in facilitating
      recovery. These treatments are often combined with a psychoeducational approach
      that essentially reteaches the patient his or her life story.

PMID- 16791780
TI  - Psychogenic (nonepileptic) seizures.
AB  - Psychogenic (nonepileptic) seizures are among the most common and serious of all
      psychogenic neurological disorders. They account for approximately 20% of all
      intractable seizure disorders referred to comprehensive epilepsy centers and
      present with a reported annual incidence of approximately 4% that of true
      epilepsy. These events are serious and disabling. Indeed, compared with patients
      with true epilepsy, patients with psychogenic seizures exhibit more frequent,
      severe, and disabling seizures as well as a poorer quality of life. The diagnosis
      and management of psychogenic seizures remain challenging, although advances in
      video electroencephalographic (EEG) monitoring have improved the ability of
      physicians to identify these disorders accurately. The prognosis of these
      patients is still relatively poor, and a good outcome seems dependent on a young
      age at diagnosis, early diagnosis, less severe psychological comorbidities, and
      continued follow-up and management by the diagnosing neurologist or clinician.
      Additional psychological or psychiatric assessment may be beneficial,
      particularly in elucidating the etiology of the disorder as well as identifying
      comorbid disorders, and may help in the long-term management of these patients.
      This review presents the history, epidemiology, differential diagnosis, and
      management of psychogenic seizures, with particular attention to the use of
      diagnostic testing, including video EEG monitoring.

PMID- 16791781
TI  - Psychogenic gait disorders.
AB  - Psychogenic disorders of posture and gait are common and are the major
      manifestation in 8 to 10% of patients with psychogenic movement disorders. The
      colorful history of these disorders is reviewed. Anxiety and depression are the
      commonest psychological accompaniments of functional gait disorder in
      contemporary practice. The particular case of the cautious gait and its flip
      side, "fear of falling," are considered in more detail. Common presentations for
      somatoform disorders and malingering are also described. It is often possible to
      make this diagnosis based on recognition features and gait observation.
      Incongruous neurologic signs are commonly found, and several features are so
      typical as to be nearly diagnostic. Caveats and pitfalls in diagnosis based on
      observational features are noted. In particular, the cautious gait is often the
      presenting feature of an older patient with an organic balance impairment. An
      approach to the patient with psychogenic gait disorder is described. Although the
      nature of the problem is often quickly apparent in such patients, the optimal
      management is a challenge. Dramatic cures still occur, and some patients respond
      quickly to psychological management and rehabilitation therapies, but persistence
      for more than 6 to 12 months is frequently associated with an unfavorable
      prognosis and long-term disability. The outcome studies are reviewed.

PMID- 16791782
TI  - Psychogenic disorders: a pragmatic approach for formulation and treatment.
AB  - Four perspectives can provide a comprehensive yet flexible approach to the
      evaluation of a patient in distress with a psychogenic disorder. Each individual
      patient will have a different combination of the four perspectives that formulate
      the patient's problems. The perspectives identify the patient with a psychogenic
      disorder as a patient who is a composite of personal vulnerabilities and
      strengths but afflicted with diseases, struggling through life events, and
      motivated to behave for various reasons. Each individual perspective has its own
      logical process for evaluation and subsequently directed treatment. Although the
      perspectives are complementary, they each remain distinct and essential to the
      formulation of a patient's disability. This comprehensive and integrated
      formulation of a patient supports an approach to complex psychogenic cases that
      defy a simple list of diagnoses and nonspecific treatments. The patient does not
      have to fit into one theoretical approach to receive an available treatment. The
      treatments prescribed are now designed from the individual formulation and
      relevant perspectives.

PMID- 16791783
TI  - [Gymnastic school sport injuries--aspects of preventive measures].
AB  - INTRODUCTION: Gymnastic school sport injuries account for a significant morbidity
      and mortality among children and adolescents. Preventive issues may be derived
      from a thorough in-depth analysis of the pattern and circumstances of gymnastic
      injuries. METHODS: During a school year among 3993 schools in 43 889 classes with
      993 056 pupils 2234 school sport injuries have been reported to the Gemeinde
      Unfall Versicherung (GUV) Niedersachsen, Germany. RESULTS: Gymnastic sport
      injuries account for 18 % (403 accidents), which is second after ball sports
      injuries. Regarding the distribution of the gymnastic disciplines, vault was the
      major discipline with 34 %, followed by floor exercise (21.3 %), mini- and
      competition trampoline (16.8 %), and parallel bars (8.2 %). The analysis of the
      type of injury during vault accidents revealed contusion (31 %) as the
      predominant injury, followed by sprains (15.4 %), and fractures (15.4 %). Floor
      exercise injuries distributed among distorsions (26.7 %), contusions (18.6 %),
      muscle tears (14 %). Back injuries especially of the cervical and thoracic spine,
      accounted for 40 % of all their injuries. Minor head injuries account for 4.7 %
      of all floor exercise injuries. Mini-trampoline injuries distribute among
      contusions (30 %), fractures (22.5 %), distorsions (7.5 %). 21.8 % collisions
      were noted against a box in comparison to 6.8 % in case of the horse. CONCLUSION:
      Gymnast injuries account for a significant number of all school sport related
      injuries. Vault and floor exercise account for the vast majority of all injuries,
      with alarming high numbers of spine injuries during floor exercise and mini
      trampoline. A preservation of a high level of attention during a sport lesson,
      safety measures including appropriate mats and landing zones are mandatory to
      reduce injuries. Muscle injuries and ankle sprains can be prevented by a
      prospective proprioceptive training intervention to be implemented in school
      sports.

PMID- 16791784
TI  - [Results of hip arthroscopy in sports related groin pain].
AB  - INTRODUCTION: The study analyses the intraoperative findings and the clinical
      results of hip arthroscopy in sports related groin pain. METHODS: Between june
      1998 and october 2002 we performed hip arthroscopy in 30 athletes (12 female, 18
      male) with a history of sports related groin pain. Their average age was 36 (20
      to 68) years. All patients had a clinical follow-up- examination at an average of
      20 (12 to 48) months postoperative. The result was rated using the Larson-Score.
      RESULTS: We found a lesion of the acetabular labrum and performed a partial
      resection at 17 patients (57 %) (synovitis: n = 28 [93 %] loose bodies: n = 6 [20
      %] torn ligamentum teres: n = 4 [13 %], others: n = 2 [6 %]). 11 patients (37 %)
      had a cartilage degeneration grade II in the Outerbridge classification (III
      degrees : n = 9 [30 %], I degrees : n = 4 [13 %], 0 degrees : n = 6 [20 %]).
      Preoperative 14 patients (47 %) complained severe groin pain (moderate: n = 14
      [47 %], slight: n = 2 [6 %]) against only 3 patients (10 %) with severe groin
      pain at the follow-up examination (moderate: n = 11 [37 %], slight: n = 16 [53
      %]). Following hip arthroscopy 28 patients (94 %) returned to full sports
      activity. The Larson-Score was increased significantly (p < 0.05) rating 43 (10
      to 64) points preoperative to 59 (28 to 80) points at the follow-up. DISCUSSION:
      We found that persistent sports related groin pain was frequently caused by an
      intraarticular hip disorder. Following hip arthroscopy pain could be reduced in
      most patients as a return to full sports activity.

PMID- 16791785
TI  - [Avascular necrosis of the capitate in athletes].
AB  - The possibility of osteonecrosis of the carpal bones should always be considered
      when athletes present with pain of unknown origin in the hand and wrist, in
      particular, if they are participating in sports such as gymnastics or weight
      lifting that involve extreme loading of the wrist with axial compression and
      microtrauma. This sort of extreme loading of the wrist combined with a
      constitutionally "weak" blood supply to the individual carpal bones may lead to
      the formation of osteo-necrotic zones. A treatment method that can produce
      excellent results, depending on the pathomorphology, is available in the form of
      vascularized bone grafting.

PMID- 16791786
TI  - Collateral damages of pseudo-scientific quarrels.

PMID- 16791787
TI  - Artificial classification and the study of human variation.

PMID- 16791788
TI  - Did Mendel actually trick?

PMID- 16791789
TI  - Does the physical state of the cytoplasm globally control cellular activity?

PMID- 16791790
TI  - Persistence of transgenic and not transgenic extracellular DNA in soil and
      bacterial transformation.
AB  - The study of the fate of transgenic and not transgenic extracellular DNA in soil
      is of extreme relevance because the soil extracellular DNA pool represents a
      genetic reservoir that could be utilized as a source of food by any heterotrophic
      microorganism or genetic information by recipient eukaryotic and prokaryotic
      cells. Several data have clearly evidenced that extracellular DNA could persist
      in soil for long time maintaining a sufficient integrity of the molecule. Recent
      microcosm studies under laboratory conditions have evidenced that extracellular
      DNA molecule could be leached or raised up by capillarity. The persistence and
      movement of extracellular DNA molecule in soil suggest that the genetic
      information of extracellular DNA could be taken up by microorganisms temporarily
      and spatially separated. Several authors have studied the persistence and
      transformation efficiency of the extracellular DNA in soil demonstrating that
      there is a sharp discrepancy between its biological efficiency and its
      persistence; fragments of target DNA were detected after a long time in soil but
      no transformations were determined probably because the genetic information
      originally present in the complete DNA molecule could be lost by degradation. It
      is also important to underline that the frequency of gene transfer in soil is
      markedly limited by the few number of bacteria able to develop competence and
      that this physiological state is reached only under certain conditions.
      Furthermore the dilution of the transgene in the soil extracellular DNA pool
      drastically decreases chances for the uptake of the transgene. Anyway the
      importance of transformation in evolutionary terms, represents a valid reason to
      continue the investigation on the fate of extracellular DNA in soil.

PMID- 16791791
TI  - Many ways to die: passive and active cell death styles.
AB  - In multicellular organisms, cells may undergo passive, pathological death in
      response to various environmental injuries, or actively decide to self-destroy in
      order to ensure proper physiological morphogenesis, preserve tissue homeostasis
      and eliminate abnormal cells. While the passive cell demise occurs in an
      accidental, violent and chaotic way, corresponding to "necrosis", the active auto
      elimination, defined "programmed cell death" (PCD), is executed in planned
      modalities. Different PCD pathways have been described, such as apoptosis,
      autophagic death, para-apoptosis and programmed necrosis. However, death patterns
      may overlap or integrate, providing a variety of cellular responses to various
      circumstances or stimuli. The consequences for the whole organism of necrosis and
      PCD are quite different. In the case of classical necrosis, cytosolic
      constituents chaotically spill into extracellular space through damaged plasma
      membrane and provoke an inflammatory response, while in most PCDs the cellular
      components are safely isolated by membranes, and then consumed by adjacent
      parenchymal cells and/or resident phagocytes without inflammation. Thus, whereas
      the necrotic cell removal induces and amplifies pathological processes, the
      elimination of PCD debris may remain virtually unnoticed by the body. Otherwise,
      alterations of PCD controls may be involved in human diseases, such as
      developmental abnormalities, or neurodegenerative, autoimmune and neoplastic
      affections, whose treatment implies the complete understanding of cell suicide
      processes. In this review, the cellular death patterns are focused and their
      significance discussed.

PMID- 16791792
TI  - Complexity and information in regular and random phyllotactic patterns.
AB  - In biology, the theory of information has been used to study the degree of order
      of many living systems. Different concepts of entropy have been applied to the
      analysis of phyllotaxis. In the present paper we will determine the degree of
      order of disorganized patterns by using informational entropy concepts deduced
      from the work of Brillouin, Shannon, and Yagil. As case studies, we will apply
      these concepts of entropy to the disorganized patterns found in mutants of
      Arabidopsis. The calculation of entropy gives a precise idea of the degree of
      order of a phyllotactic system.

PMID- 16791793
TI  - The origin of phage virology.
AB  - The history of bacteriophage (phage) had its start in 1915, when Twort isolated
      an unusual filterable and infectious agent from excrete of patients struck by
      diarrhoea; this discovery was followed by an analogous, and probably independent,
      finding of d'Herelle in 1917. For several years phage research made scant
      progress but great attention was paid to the question of phage nature, which saw
      the contrast between d'Herelle and Bordet's views (living against chemical
      nature, respectively). This situation changed with the independent discovery of
      lysogeny, in 1925, thanks to Bordet and Bail: this phenomenon was considered of
      genetical origin, a view that Wollman interpreted by assimilating the properties
      of phage to those of gene (according to a previous idea of Muller). In the 1930s,
      Burnet's work opened a new era by demonstrating the occurrence of several species
      of phages and their antigenic property. In the same period, the physical and
      chemical characteristics of these viruses were disclosed thanks, in particular,
      to the work of Schlesinger, who first demonstrated that a virus (phage) was
      constituted of nucleoproteins. The peculiarity of phage was finally shown after
      the invention of electron microscope: H. Ruska, in 1940, and Anderson and Luria
      in the next years, obtained the first images of tailed phages, a finding that
      strongly helped the investigation on the first steps of the infection process.
      The decisive impulse to phage virology came from Delbruck, a physicist who
      entered biology giving it a new arrangement. The so-called "phage group"
      assembled brilliant minds (Luria, Hershey and Delbruck himself, and later a dozen
      of other scientists): this group faced three fundamental questions of phage
      virology, i.e., the mechanisms of attack, multiplication and lysis. In ten years'
      time, phage virology became an integrant part of molecular biology, also thanks
      to the discovery of the genetical properties of DNA: in such scientific context,
      Delbruck, Luria and Hershey's works emerged for the absolute excellence of their
      results, which led such scientists to Nobel prize. Lysogeny was however neglected
      by the phage group: this singular property shared by bacteria and phages was
      instead investigated by Lwoff's group, in Paris, and explained in its fundamental
      features during the 1950s. The "phage's saga" has gone on being an important
      division of molecular biology till today, and its history is far from being over.

PMID- 16791794
TI  - Towards an understanding of the role of forces in carcinogenesis: a perspective
      with therapeutic implications.
AB  - Carcinogenesis may aberrantly have as its source an underlying dynamic which
      likely operates in accord with or is expressive of a universal principle of
      force. This drive can be seen as a type of necessary completion of force
      configurations giving forth a force-based, completing guidance or dyneotaxis.
      This completing guidance is a completing communication. Aberrations of this drive
      can manifest as incomplete communication arising from incomplete or non-uniform
      force-configurations throughout different levels of organization within the
      organism. Such non-uniformities of force-configuration manifest themselves
      through intra- and intercellular distortion. This is represented by changes or
      distortions within cellular and tissue architecture, or shape, occurring through
      and enabling a non-uniform loosening. Cycles of non-uniform loosening and
      distortion would generate a progressive disruption or aberration in an otherwise
      further adhesively completing, thereby further stabilizing, dyneotaxis.
      Carcinogenesis ensues as an aberrant means to re-establish a uniformity or
      symmetry of adhesive and mechanical forces in such tissues, and within the
      genome. However, it rather results in a further loosening-based reorganization or
      reshaping. This would be a manifestation of a still further non-uniformity of
      forces. Uncontrolled mutagenesis, itself stemming from genomic distortion, is
      also seen as a process that could lead to loosening and further distortion
      throughout the cell, and thereby, a contributor to carcinogenesis if a
      transcellular, globally completive or uniform adhesiveness cannot be maintained.
      A therapeutic approach could be employed to reverse such a cycle of loosening and
      distortion within cellular and tissue organization. The developmental reversal of
      carcinogenesis would be the consequence. Such an approach could be through the
      application of a coherent, uniform and united array of guiding mechanical and
      electromagnetic forces. The deeper consequence would be the re-establishment of a
      global, cancer-countering, uniform or symmetrical, guiding adhesiveness via and
      dependent on a complete and non-distorted network of cellular and intercellular
      structures, further completing, and thus further stabilizing, such structures in
      the process.

PMID- 16791795
TI  - Reduction of the crop plant allergenicity due to soil treatment with Bacillus
      oligonitrophilus KU-1 strain.

PMID- 16791796
TI  - The role of 18F-FDG PET in oncology: clinical and resource implications.

PMID- 16791797
TI  - Small animal imaging using a conventional gamma camera exemplified in studies on
      the striatal dopaminergic system.
AB  - BACKGROUND: Small animal imaging has recently been the subject of increasing
      interest and specific imaging devices in particular for positron emission
      tomography (PET) have been developed. To bypass limitations arising from high
      acquisition costs and dependence on an in-house cyclotron unit inevitably
      associated with PET, a conventional gamma camera has been equipped with a pinhole
      collimator and used to visualize striatal pre- and post-synaptic dopaminergic
      function in rats measured by the dopamine transporter ligand [123I]beta-CIT and
      the dopamine D2/dopamine D3 receptor ligand [123I]IBZM. In order to precisely
      estimate brain regions of low radioligand uptake, single photon emission computed
      tomography (SPECT) images were coregistered onto an MRI template. MATERIAL AND
      METHODS: Our pinhole SPECT/MRI approach has been employed in animal models of pre
      and postsynaptic dopaminergic dysfunction. The physical characteristics of the
      scanner, the tracer kinetics and modelling as well as image postprocessing have
      been addressed and associated intrinsic problems and constraints discussed.
      CONCLUSIONS: An outlook has been provided on the application of pinhole SPECT and
      MRI coregistration towards non-invasive investigations of drug-receptor
      interactions and binding characteristics of newly developed radiopharmaceuticals.

PMID- 16791798
TI  - Prognostic utility of carotid ultrasound and cardiac SPECT imaging in coronary
      artery bypass patients.
AB  - BACKGROUND: The aim of our study was to evaluate the role of myocardial perfusion
      imaging (MPI) and common carotid artery intima-media thickness (CCA IMT) in the
      prognosis of patients with coronary artery disease referred for coronary artery
      bypass surgery (CABG) in a newly made prognostic model. MATERIAL AND METHODS: 63
      patients (age 60.36 +/- 8.28 years) with angiographically established coronary
      artery disease referred for CABG were evaluated for: age, smoking, family
      disposition, dyslipidaemia, arterial hypertension, obesity, diabetes mellitus,
      previous myocardial infarction and revascularization. Patients underwent nitrate
      enhanced Gated SPECT myocardial perfusion imaging, with 17-segment analysis for
      calculation of perfusion scores and viability index. Common carotid artery IMT
      was measured by B-mode ultrasound. Patients were followed for cardiovascular
      events 12 months after CABG. RESULTS: The obtained data reported mean values of
      left ventricular ejection fraction (LVEF) 46.2 +/- 14.4%, viability index 0.76 +/
      0.55, SRS 17.76 +/- 13.81 and summed nitrate score 12.89 +/- 10.36. Ultrasound
      detected CCA IMT 0.90 +/- 0.24 mm, with increased value in 67.2% and presence of
      carotid plaques in 27.1% of pts. We registered 14 events and 8.8% mortality rate.
      Multiple regression modelling showed bilateral carotid plaque presence as a
      predictor of total events. Viability index and CCA IMT have been found as
      independent death predictors. CONCLUSIONS: Myocardial perfusion viability index
      and CCA IMT are predictors, independently associated with prognosis of patients
      referred for CABG.

PMID- 16791799
TI  - Radionuclide assessment of lower limb perfusion using 99mTc-MIBI in early stages
      of atherosclerosis.
AB  - BACKGROUND: The aim of the work was a scintigraphic evaluation of regional blood
      supply of thigh and calf muscles using 99mTc-MIBI as a radiopharmaceutical, in
      early stages of atherosclerosis revealed during ultrasonographic examination of
      lower limbs, in patients without typical clinical symptoms of chronic ischaemia
      of lower limbs and with preserved normal Doppler spectrum of blood flow.
      Moreover, basic relations between early signs of lower limb atherosclerosis and
      abnormal myocardial perfusion, as well as asymptomatic hypoperfusion of lower
      limbs, were analysed. MATERIAL AND METHODS: Stress and rest radionuclide study of
      lower limb muscles and myocardium using 99mTc-MIBI was performed in 47 men, who
      were divided into two groups based on ultrasonography results. The first group
      (group I) comprised 22 patients with early atherosclerotic changes in peripheral
      vessels and the second (group II) comprised 25 people with normal arteries. For
      the purposes of quantification of study results normal values of regional blood
      supply and indices of asymmetry at levels of thighs and calves, as proposed by
      Segall et al., were applied. Myocardial scintigrams were evaluated according to
      widely accepted rules (visual and semi quantitative--normative analysis).
      RESULTS: Mean values of stress and rest perfusion indices of thighs as well as
      calves in gr. I were statistically significantly lower (p < 0.001) than in gr.
      II. Incidence of asymmetry in the stress perfusion of calves and thighs was
      statistically significantly higher (p = 0.04) in patients with atherosclerotic
      changes as compared with the control group. Abnormal myocardial perfusion was
      found in 77% of patients from group I and in 28% from group II (p = 0.001).
      Reversible, stress induced ischaemia was found in 59% and 16%, resp. (p = 0.01).
      CONCLUSIONS: 1. Radionuclide study revealed a reduced stress as well as rest
      perfusion of lower limb muscles in clinically asymptomatic patients with
      atherosclerotic changes of lower limb vessels of low degree and a preserved
      normal Doppler blood flow spectrum. 2. Presence of early atherosclerotic changes
      in lower limb vessels implies a higher probability of asymptomatic hypoperfusion
      of lower limbs as well as coronary artery disease.

PMID- 16791800
TI  - Comparative analysis of 99mTc-depreotide and 99mTc-EDDA/HYNIC-TOC thorax
      scintigrams acquired for the purpose of differential diagnosis of solitary
      pulmonary nodules.
AB  - BACKGROUND: Aiming at comparison of diagnostic efficacy of 2
      radiopharmaceuticals: 99mTc-depreotide (Neospect, Amersham) and 99mTc-EDDA/HYNIC
      Tyr3-octreotide (Tektrotyd, Polatom), in differentiation between malignant and
      benign etiology of solitary pulmonary nodules (SPNs), radionuclide studies with 2
      radiotracers were performed in 18 patients. MATERIAL AND METHODS: For both
      radiopharmaceuticals the same acquisition and processing protocols were applied.
      Studies were acquired with SPECT technique, after administration of 740 MBq of
      activity. Scintigrams were assessed visually, as: positive (+), equivocal (+/-)
      and negative (-). Additionally, uptake intensity of both radiotracers in nodules
      was assessed semiquantitatively, using a tumour-to-background ratio. Verification
      of scintigraphic results was based in 14 cases upon a pathological examination of
      tumour samples (histopathology) and in the remaining 4 - on clinical observation
      and bacteriological studies. RESULTS: Normal scintigrams obtained with both
      radiopharmaceuticals differed significantly. 99mTc-depreotide was markedly
      accumulated in spine, sternum, ribs and lungs (mean lung/heart ratio = 2.2). This
      accumulation was not observed on 99mTc- -EDDA/HYNIC-TOC scintigrams (mean
      lung/heart ratio = 0.7). In 6 patients a malignant etiology--lung cancer--was
      revealed (5--adenocarcinoma, 1--squamous cell) and the other 12 cases turned out
      to be benign (4 hamartomas, 3 tuberculomas, a tuberculous infiltrate, an alien
      body with inflammatory reaction, a hyperplasia of lymphatic tissue and 2 cases of
      unknown etiology, from which one had a stable size and the other resolved during
      a 6 month observation period). In all 6 cases of lung cancer positive results
      were obtained with both tracers. Moreover, in 2 patients metastases in
      mediastinum could be observed on scintigrams obtained with both
      radiopharmaceuticals. From among 12 cases of benign etiology 6 99mTc-depreotide
      scintigrams were true negative, 1--equivocal and 5--false positive, whereas 6
      99mTc-EDDA/HYNIC-TOC scintigrams were true negative, 4--equivocal and 2 false
      positive. Moreover, 99mTc-depreotide additionally revealed mediastinal and hilar
      lesions in 9 patients with benign lesions and 99mTc-EDDA/HYNIC-TOC - in 8. A
      visual comparison of scintigrams revealed a higher quality of 99mTc-Depreotide
      images in comparison with 99mTc-EDDA/HYNIC-TOC ones. 99mTc-Depreotide showed a
      higher than 99mTc-EDDA/HYNIC-TOC accumulation in lung tumours compared with blood
      pool (heart) - 4.5 (s.d. 1.05) and 1.8 (s.d. 0.29), respectively (p < 0.05).
      However, mean values of tumour-to-lung-background ratio were equal for both
      radiotracers (2.2 in malignant and 1.4 in benign lesions, respectively). A
      statistically significantly higher non-uniformity of counts inside lung
      background regions was found on 99mTc-EDDA/HYNIC-TOC scintigrams than on 99mTc
      depreotide ones (16.4% vs. 11.4%; p < 0.01). CONCLUSIONS: Although both
      radiopharmaceuticals show similar diagnostic efficacy in differentiation of SPNs,
      a tendency toward a higher number of false positive results on 99mTc-depreotide
      scintigrams probably leads to a lower specificity. Better statistical quality of
      99mTc-depreotide scintigrams facilitates their interpretation and a distinct
      outline of lungs simplify localization of lesions. A substantial number of false
      positive lesions in mediastinal and hilar regions in patients without a
      neoplastic process hamper the usefulness of both radiotracers for effective
      detection of lung cancer metastases to lymph nodes.

PMID- 16791801
TI  - Technetium-99m-tetrofosmin in diagnosis of breast cancer and axillary lymph node
      involvement.
AB  - BACKGROUND: The aim of this study was to evaluate the accuracy of breast cancer
      seeking agent Tc-99m-Tetrofosmin in the detection of breast malignancy and
      axillary lymph node metastases. MATERIAL AND METHODS: Twenty-eight female
      patients (mean age 52.4) with 30 breast lesions suspected of malignancy were
      enrolled in the study. All the patients underwent clinical investigation, Tc-99m
      Tetrofosmin scintimammography (SMM), mammography (MM) and biopsy/surgery for
      final histopathologic diagnosis. Patients were injected intravenously with 555
      MBq of Tc-99m Tetrofosmin, cubitally, in the contralateral arm to the side of
      suspicious lesion. Seven minute static scans or at least 2.0 million counts were
      obtained using single head gamma camera (Orbiter 75, Siemens). Planar images were
      acquired in left and right prone lateral view as well as in the supine position
      for an anterior view of chest and axillary region. RESULTS: SMM scans of 30
      breast lesions were compared to the definitive histopathology findings (HP) using
      decision matrix. In the group of 23 patients with positive SMM scans 19 had
      breast malignancy: 15 infiltrating ductal cancer, three patients with one
      infiltrating lobular, one papillary, one colloidal cancer and one patient with
      cystosarcoma phyllodes-malignant type. SMM detected primary breast malignancy
      with 95% sensitivity, 60% specificity and 83% accuracy. Axillary dissection was
      performed in 19/20 with malignant disease. The number of lymph nodes extracted
      and HP evaluated varied from 4 to 23 per patient. Metastatic involvement was
      confirmed by HP in 9 out of 20 patients. SMM detected axillary metastases with
      55% sensitivity and 80% accuracy. CONCLUSION: Our results showed that SMM might
      be useful as a complementary test to improve the sensitivity and specificity of
      conventional imaging modalities, although SMM in the staging of breast carcinoma
      was less reliable. Further studies to evaluate the role of SMM in metastatic node
      involvement are necessary.

PMID- 16791802
TI  - Diagnostic role of 18F-FDG PET in gastric MALT lymphoma.
AB  - BACKGROUND: The aim of the study was to evaluate the usefulness of 18F-FDG-PET in
      patients with gastric lymphoma, in particular those affected by mucosa-associated
      lymphoid tissue (MALT) type and aggressive gastric non-Hodgkin's lymphoma (NHL).
      MATERIAL AND METHODS: The study group consists of 15 patients with a previous
      diagnosis of gastric NHL referred to our PET centres in Bologna Hospital and
      Rovigo Hospital, Italy, in the period 2003-2004. In 9/15 patients the subsequent
      histological evaluation was consistent with a gastric MALT lymphoma, while
      aggressive gastric NHL was diagnosed in the other 6/15. PET scan was carried out
      in patients with known active disease in order to stage or re-stage disease prior
      to treatment or in patients in complete clinical remission to monitor disease
      during follow up. Patients were considered in complete clinical remission if free
      from disease for at least 8 months after chemotherapy or surgery.18F-FDG PET was
      performed following standard procedures. RESULTS: Overall 18F-FDG-PET was true
      positive in all cases of gastric MALT and non-MALT aggressive NHL with known
      active disease, while no pathological 18F-FDG uptake was evident in the subjects
      who were in complete clinical remission. The degree of 18F-FDG uptake (mean
      SUVmax values) in MALT lymphoma was much less intense in comparison to aggressive
      gastric NHL, suggesting a prognostic role of SUV calculation in gastric
      lymphomas. CONCLUSION: Our data demonstrate the significant accuracy of 18F-FDG
      PET in detecting active disease in gastric lymphoma of both MALT and non-MALT NHL
      type. A higher SUV value appears to be related to a more aggressive disease.

PMID- 16791803
TI  - Significance of posture and workload in exercise renography.
AB  - BACKGROUND: Exercise-induced alteration in renal function has been described in
      patients with essential hypertension. The aim of our study was to assess the
      significance of adopting a supine posture and the degree of workload required to
      induce these changes in patients with essential hypertension. The second aim was
      to assess whether the severity of hypertension had any influence on the
      development of exercise related renal dysfunction. MATERIAL AND METHODS: Fifteen
      patients were studied (nine patients with mild and untreated hypertension and six
      patients with drug resistant hypertension). Exercise renography was carried out
      using a cycloergometer with the patient lying in supine posture and a target
      exercise rate of 20 bpm over baseline rate. Each patient was injected with 100
      MBq of 99mTc-MAG3 and renography was carried out for 20 minutes. Renography was
      repeated in rest condition only when an abnormality was observed in exercise
      scans. RESULTS: Exercise renography was normal in 12 patients, while in 3
      patients minor abnormalities were observed during exercise related to a minimal
      degree of pelvic dilatation. These changes remained substantially unmodified at
      rest. In none of the 15 patients did we find positive studies (i.e. reversible
      exercise induced prolongation of tracer transit caused by cortical retention).
      There was no difference in the results between patients with mild or severe
      hypertension. CONCLUSIONS: Our results are different from previous reports on
      exercise renography since different groups have demonstrated exercise-induced
      renal dysfunction in the majority of patients with essential hypertension. The
      main differences between our protocol and that adopted in the literature relate
      to posture during exercise (upright vs. supine) and degree of workload (minor in
      supine exercise with less workload). These differences may have contributed to
      our results but further and larger studies are required to address the
      pathophysiological basis of exercise-induced alteration in renal function in
      association with essential hypertension.

PMID- 16791804
TI  - Results of a five-year study of 99mTc DMSA renal scintigraphy in children and
      adolescents following acute pyelonephritis.
AB  - BACKGROUND: Renal scintigraphy, generally using 99mTc-DMSA, is the accepted
      reference standard for detection of renal cortical changes. The timing of the
      test, i.e., whether an acute 99mTc-DMSA scan, a follow-up only or both scans
      should be performed, however, remains open to discussion. In our study, a six
      month follow- up DMSA scan was performed in all the children diagnosed with a
      first attack of acute pyelonephritis (APN) in two large paediatric clinics of
      Charles University's 3rd School of Medicine in Prague during a five-year period.
      All diagnoses were confirmed by a paediatric nephrologist. MATERIAL AND METHODS:
      382 children (267 girls, 115 boys) aged between 7 months and 19 years were
      included in the study. For analytical purposes, the patients were divided into 4
      age groups: I--less than 1 year of age, II--1-5 years, III--5-10 years, and IV-
      10-19 years. In all children younger than five years, a micturition
      cystourethrogram (MCUG) for detection of vesicoureteric reflux (VUR) was
      performed between one and three months after the APN episode. Static renal
      scintigraphy, using an HR collimator with parallel holes was performed using a
      planar Gamma camera MB 9200 (Gamma Budapest) in all children six months after
      APN, with a complement of pinhole images, SPECT or PSPECT of the kidneys.
      RESULTS: 1. In group I, all four children with positive VUR on MCUG had a
      pathological DMSA scan, while only two of the 32 patients with negative VUR had a
      pathological DMSA. 2. In group II, 17 children had VUR on MCUG, six of them with
      a pathological and 11 with a normal DMSA scan. Most of the 221 children without
      VUR had a normal DMSA scintigraphy; pathological findings were present in 17
      children only. 3. In group III, all children with VUR, but only 5 out of 53
      without VUR, had a pathological DMSA scan. 4. Five out of 50 children in group IV
      had a pathological DMSA. CONCLUSIONS: APN occurred most frequently in group II
      (62.3%, or 238 children) and ranged between 10-15% in the remaining groups. APN
      was found very frequently in boys less than one year old and showed a marked
      decrease with increasing age. Among girls, however, APN incidence was observed to
      increase with age. Pathological renal changes were present in children with, as
      well as without, VUR. The incidence of pathological DMSA findings six months
      after APN was relatively low (44/382 patients, or 11.5%). Regular monitoring of
      these children is very important for detection of renal scarring.

PMID- 16791805
TI  - Simultaneous dynamic study of gastric emptying and changes of serum levels of gut
      hormones in patients after peptic ulcer surgery.
AB  - BACKGROUND: The aim was to examine the influence of different modalities of
      peptic ulcer surgery on the gastric emptying (GE) pattern and related serum level
      changes of selected gut hormones. MATERIAL AND METHODS: Fifty eight subjects were
      examined. In 48 of them peptic ulcer surgery was performed at least six months
      before the examination: Billroth I (B1) in 11, Billroth II (B2) in 16, B1 with
      the selective vagotomy--Harkins 1 (H1) in 9 and B2 with the selective vagotomy-
      Harkins 2 (H2) in 12. Ten healthy volunteers (C) were also examined. RESULTS: The
      results of gastric emptying showed that the lag phase duration was inversely
      related to the GE rates, and the GE pattern was linear in both controls (C) and
      in operated patients, except in B2 group, in which the GE pattern was
      exponential. In comparison with C group, GE was slower in B1, H1 and H2 groups,
      and faster in B2 group. The plasma gastrin values in C group, showing two peaks,
      were higher in relation to other groups. In relation to C group, higher values of
      motilin were obtained in patients after the selective vagotomy. The plasma
      somatostatin values recorded in B1 and H1 groups, showing the marked peaks, were
      higher in relation to C group. In relation to C group the highest plasma
      neurotensin values were obtained in B2 group. CONCLUSIONS: In order to understand
      entirely the influence of peptic ulcer surgery on the GI function, further
      research of the role of specific hormones and neuropeptides is needed, which
      would enable more precise selection of the therapy in order to prevent
      postvagotomy and postgastrectomy syndromes.

PMID- 16791806
TI  - Specific 99mTC-HEPIDA hepatic clearance--essential value ranges from a clinical
      stand-point.
AB  - BACKGROUND: Determinations of plasma 99mTc-HEPIDA clearance (ClPl) have been
      performed in some centres for 30 years to assess liver parenchyma damage, mostly
      for monitoring of organ performance in the course of various diseases. The main
      disadvantage of such a procedure rests with the fact that elimination of the
      compound from the system occurs not only via the liver and gall ducts, but also
      via the urinary route; the contribution of the latter compound being quite
      variable. This circumstance may lead to false assessment of liver parenchyma
      performance. A method has been developed therefore for assessment of specific
      hepatic clearance of 99mTc-HEPIDA (Cl(Hp)). Using this method it was demonstrated
      that results of Cl(Hp) correlated better with independently assessed degrees of
      liver impairment than did the values of ClPl. MATERIAL AND METHODS: To delineate
      ranges of Cl(Hp) that would provide valuable clinical information 134 individuals
      were studied, of whom 48 served as healthy controls and 86 had varying degrees of
      livers function impairment, resulting from various chronic diseases affecting the
      organs functional capacity. The latter was assessed on the basis of a series of
      commonly used biochemical indicators. RESULTS AND CONCLUSIONS: For delineation of
      meaningful ranges of 99mTc-HEPIDA specific hepatic clearance ROC curve method was
      used. The following results were obtained: Cl(Hp) >or= 150 ml min(-1) 1.72 m(-2)-
      excludes with high probability presence of substantial liver parenchyma damage;
      Cl(Hp) <or= 120 ml min(-1) 1.72m(-2)--indicates a substantial impairment of liver
      function (damage). Values of Cl(Hp) <or= 90 ml min(-1) 1.72 m(-2) are highly
      specific for serious liver damage, of intensity typical for cirrhosis of the
      organ.

PMID- 16791807
TI  - The role of quantitative Tc-99m-MIBI gated SPECT/F-18-FDG PET imaging in the
      monitoring of intracoronary bone marrow cell transplantation.
AB  - BACKGROUND: A lot of unresolved questions still exist concerning the exact
      mechanism of the beneficial effects of bone marrow cell (BMC) transplantation for
      myocardial regeneration. The aim of this communication is to report the cases of
      patients with and without post-transplantation left ventricular function
      improvement. MATERIAL AND METHODS: To this study we included consecutive patients
      with irreversible damage after a first acute ST-elevation myocardial infarction
      treated by coronary angioplasty with stent implantation. The irreversible damage
      was identified by dobutamine echocardiography and confirmed by rest gated Tc-99m
      MIBI gated SPECT and in the majority of patients by F-18-FDG PET imaging as well.
      Using 4D-MSPECT software, we quantified MIBI/FDG uptake and gated SPECT left
      ventricular ejection fraction, end-diastolic/end-systolic volumes (LVEF, EDV/ESV)
      before BMC therapy and 3 months later. RESULTS: The results obtained in the
      initial group of patients in this study (27 patients in the BMC treated group, 16
      patients in the control group) have been published previously [Eur J Nucl Med
      2005; 32 (Suppl 1 ): S46]. Among the BMC group, we identified 13 responders to
      therapy with average LVEF improvement from 43.3% +/- 11% to 51.4% +/- 10.4% and
      EDV/ESV improvement from 145 ml/84 ml to 133 ml/67 ml. The remaining 14 patients
      were non-responders to therapy with no significant change in LVEF (39.1% +/- 8.1%
      versus 39.8% +/- 7.4%), the EDV/ESV increased from 166 ml/105 ml to 188 ml/116
      ml. Responders to the cell therapy had prevailing MIBI uptake in the range of 31
      50% of maximum in the infarction territory. On the other hand, non-responders to
      BMC therapy had prevailing MIBI uptake in the range of 0-30% of maximum. Two
      cases are presented in this report. CONCLUSIONS: Further studies with a larger
      cohort of patients would be helpful to evaluate our findings. We observed strong
      interindividual differences in the effectiveness of the cell therapy. Prevailing
      residual MIBI uptake in the range of 31-50% of maximum was in the subgroup of
      responders to the cell therapy.

PMID- 16791808
TI  - Detection of sentinel lymph nodes in cervical cancer. A comparison of two
      protocols.
AB  - BACKGROUND: The aim of this study was lymphatic mapping to identify SLN in
      cervical cancer (CaCerv) with radioactive colloids, intraoperative detection with
      patent blue dye (PBD) and gamma probe (GP) and biopsy and comparison of two
      protocols. MATERIAL AND METHODS: In 54 patients with CaCerv before hysterectomy
      and lymph nodes dissection (LND) we performed preoperative lymphoscintigraphy
      utilizing 99mTc-colloid (Nanocoll, SentiScint or Nanocis), activity 40 MBq, on
      the operation day (30 women) or the day before operation (24 women).
      Gynaecologists injected 4 peritumoural injections of colloid into the cervix
      around the tumour. Scintigraphy followed 25-50 minutes (one-day protocol) or 12
      19 hours (two-day protocol) after injection. Gynaecologists also injected 4
      peritumoural injections of PBD into the cervix around the tumour. All women
      underwent SLN biopsy and LND (in average 35 lymph nodes were taken) and
      hysterectomy. SLNs (active and/or blue lymph nodes) were examined by a
      pathologist [histopathology and immunohistochemistry (IH) with detection of
      cytokeratine]. No SLN was examined without IH. RESULTS: The gynaecologists
      withdrew 123 SLNs (on average 2.27/1 patient) and in total 1898 lymph nodes (on
      average 35/1 patient). In 1 woman the tumour was inoperable. Two-day protocol,
      which involved scintigraphy, PBD and GP detected SLNs on both sides (45 SLNs) in
      17 women (70.8%), SLNs on the one side (6 SLNs) in 3 patients (12.5%) and no SLNs
      were found in 4 women (16.7%). One-day protocol detected SLNs on both sides in 23
      patients (74.1%)--63 SLNs, in 7 women on one side (25.9%)--9 SLNs. Metastases in
      SLNs (with or without metastases in other LN) were found in 21 patients (38.9%)-
      in 1 woman of stage FIGO IB1, in 1 woman of stage FIGO IB2, in 1 patient of stage
      FIGO IIIA and in all 18 patients of stage FIGO IIIB. False negative SLN detection
      was 0%. CONCLUSIONS: In SLN detection in patients with CaCerv, all 3 methods-
      scintigraphy, PBD and GP--should be used, and the success rate of SLN detection
      increases, although scintigraphy has lower significance than in SLN detection in
      malignant melanoma and breast cancer. One-day protocol had a better detection
      rate of SLN than two-day protocol. The method is promising but its results are
      not as unequivocal and optimistic as in breast cancer and malignant melanoma, and
      it is still experimental. Additional experience is necessary.

PMID- 16791809
TI  - Anomalous origin of left main coronary artery: the value of myocardial
      scintigraphic and spiral computed tomography scans.
AB  - Anomalous origin of the left main coronary artery (LMCA) from the right sinus of
      the Valsalva or the proximal right coronary artery (RCA) is one of the most
      clinically important anomalies of coronary circulation. We report the case of a
      patient with chest pain and abnormal thallium myocardial perfusion scan in whom
      the anomaly was first detected on invasive coronary arteriography. The exact
      anatomic course of anomalous LMCA was confirmed using contrast enhanced computed
      tomography.

PMID- 16791810
TI  - The role of radioisotopic methods in imaging of intervertebral disc inflammation
      in children.
AB  - The authors present the case of a 17-year-old girl, with pain over lumbar spine
      area, treated by paediatricians and rehabilitation specialists, discussing
      diagnostic imaging and laboratory examinations together with clinical
      observations. Spondylodiscitis was diagnosed after bone scintigraphy with 99mTc
      MDP, the course of disease was monitored by immunoscintigraphy amongst other
      techniques.

PMID- 16791811
TI  - The unusual cause of recurrent abdominal pain in an 11-year-old boy.
AB  - The case of an 11-year-old boy with recurrent abdominal pain is presented.
      Physiological findings were found normal during a clinical investigation, as well
      as many laboratory tests, ultrasonography and CT of abdomen. Only a high level of
      sedimentation rate and the focus of increased activity in the sacral region on
      scintigraphy using 99mTc-HMPAO (hexamethypropyleneaminooxime) labelled leukocytes
      were found. The other findings on bone scintigraphy, X-ray and MRI led to a
      deflection of the correct diagnosis. The real culprit proved to be an ingested
      foreign body (a piece of a wooden skewer) that the patient failed to reveal.

PMID- 16791812
TI  - Regional cerebral blood flow abnormalities in an epileptic boxer dog.

PMID- 16791813
TI  - Job-sharing in nuclear medicine: an 8-year experience (1998-2006).
AB  - Job-sharing is generally defined as a situation in which a single professional
      position is held in common by two separate individuals, who alternatively, on a
      timely basis, deal with the workload and the responsibilities. The aim of the
      present paper is to discuss prerequisites and characteristics of job-sharing by
      medical doctors and implications in a department of nuclear medicine. Job-sharing
      facilitates the combination of family life with professional occupation and
      prevents burnout. The time schedule applied by job-sharers is relevant: will both
      partners work for half-days, half-weeks, or rather alternatively during one to
      two consecutive weeks? This crucial choice, depending on personal as well as on
      professional circumstances, certainly influences the workflow of the department.

PMID- 16791814
TI  - International Czech and Slovak cooperation in the treatment of patients with
      differentiated thyroid cancer.
AB  - BACKGROUND: The aim of this paper is to present our experience concerning
      cooperation in the treatment of Slovak patients with differentiated thyroid
      cancer in Slovak and Czech hospitals. The objectives of this study were to
      demonstrate the means of this cooperation and the results of therapy. MATERIAL
      AND METHODS: From September 1991 to October 2005 in the Department of Nuclear
      Medicine in Ostrava 357 patients from the Slovak Republic with differentiated
      thyroid cancers (follicular and papillary) underwent complex therapy. They were
      diagnosed and operated due to the cancer (near-total thyroidectomy and removal of
      lymph node metastases) in Slovak hospitals. Then they were sent to the Department
      of Nuclear Medicine in Ostrava in the Czech Republic. In this department a
      radioiodine ablation of thyroid remnants, by means of the treatment amount of
      radioiodine of a standard activity of 3.7 GBq, was performed, and then a
      suppression and substitution therapy of thyroid hormones was started. After 3-6
      months some patients were examined by means of diagnostic whole body scintigraphy
      after application of 300 MBq 131I. Some patients were treated by means of a
      standard activity of 7.4 GBq 131I and after 5 days whole body scintigraphy (WBS)
      was performed. In both of these groups of patients the diagnostic or therapeutic
      radioiodine application was done after withdrawal of thyroid hormone treatment.
      If thyroglobulin levels were low and WBSs were negative, patients were followed
      up in the Department of Nuclear Medicine in Martin. Patients with radioiodine
      accumulated metastases were again treated with radioiodine in Ostrava. If
      indicated, external radiation therapy targeted on the neck and upper mediastinum
      was performed in the Slovak Republic, in the University Hospital in Martin. Newly
      formed lymph node metastases were surgically treated in Slovakia, too. Generally
      we have very good treatment results. Also, economically our partnership is cost
      effective. Our collaboration also successfully continues after entrance of the
      Slovak Republic and the Czech Republic to the European Union in 2004.
      CONCLUSIONS: The results of this multi-centre study show that international Czech
      and Slovak cooperation in the complex therapy of patients with differentiated
      thyroid cancers is successful, with high efficacy. The treatment results were
      very similar to therapeutic results in our patients from the Czech Republic.

PMID- 16791815
TI  - Student's plagiarism--a challenge for paramedic educators.
AB  - Student's plagiarism is a growing problem not only in the writing of controlling
      essays, but above all in the writing in BSc./MSc. diploma theses, which sometimes
      can be simply bought from ghost-writers. This is a major challenge for medical
      educators, particularly in paramedic professions. The aim of this paper is to
      overview the frequency of plagiarism among students, the factors influencing
      plagiarism, the ways of detecting it and potential countermeasures.

PMID- 16791819
TI  - Effects of a 21 day metabolic study on serum opsonic activity in female college
      students, assessed by a chemiluminescence technique.
AB  - A metabolic study to evaluate nutritional balance, in which subjects have to eat
      all the foods supplied and maintain a set schedule, is thought to be stressful
      for the subjects. The effects of stress on the immune system have been studied
      extensively. However, there are no studies of non-specific immunological changes
      during a metabolic study. Serum opsonic activity (SOA) is a direct and suitable
      indicator of non-specific humoral immunity. In this study, we used luminol
      dependent chemiluminescence (LmCL) to measure reactive oxygen species (ROS)
      generation from pooled human neutrophils as an indicator of SOA. We also measured
      serum immunoglobulin levels and plasma myeloperoxidase (MPO) activity. Eleven
      female college students took part in this 21 day metabolic study after giving
      their written informed consent. The results obtained suggest that the metabolic
      study has almost no effect on immunoglobulin levels. According to MPO levels,
      neutrophils in vivo may be deactivated to some minor extent. In contrast to these
      results, peak time (PT) and peak height (PH) of LmCL were changed significantly
      during the metabolic study. In conclusion, SOA increased during the 21 day
      metabolic study. There was no significant correlation between SOA and serum
      immunoglobulin levels on any of the study days.

PMID- 16791820
TI  - Chemiluminescent determination of total antioxidant capacity during winemaking.
AB  - The total antioxidant capacity (TAC) of five different wines (four red and one
      white) was determined in five different steps of winemaking carried out in a
      commercial wine cellar by a chemiluminescence (CL) assay. The CL method is
      suitable to determine the antioxidant capacity of beverages, and preliminary
      trials showed that the TAC immediately after the bottle was opened was greater
      than the day after (about 25% decrease). Immediate analysis or a correct sample
      storage is therefore necessary. The wines were characterized by different levels
      of total phenolics and TAC: these differences were related to grape composition
      and winemaking technologies. The TAC values were the highest immediately after
      devatting. The TAC suffered the highest decrease (30-50%) after the clarification
      procedure, which may be due to the fining agents used and to oxygen contact, then
      remained more or less constant in the subsequent steps.

PMID- 16791821
TI  - Comparison of effects of in vivo nitrogen dioxide exposure starting from
      different periods on alveolar macrophage activity, assessed by a
      chemiluminescence technique in Brown-Norway rats.
AB  - Nitrogen dioxide (NO2) has been extensively studied for its immune modulating
      effects on pulmonary cells. Alveolar macrophages (AMs) play an important role in
      pulmonary immunity. The Brown-Norway (BN) rat has been studied as a high-risk
      model of allergic diseases. In this study, BN rats were exposed to NO2 from the
      embryonic or weanling period (EP or WP, respectively). To evaluate the effects of
      NO2 exposure on pulmonary immunity, the activity levels of rat AMs were assessed
      as reactive oxygen species-generating capacity, measured by a chemiluminescence
      (CL) technique, and as cytokine-producing ability. Except for 0.2 ppm of NO2
      exposure, the CL responses of AMs obtained from the WP group at 12 weeks old were
      suppressed significantly. Changes of the cytokine-producing levels suggest that
      inflammatory reactions are terminated at 12 weeks in the EP group. Correlations
      between the CL responses and the cytokine levels reveal that NO2 exposure may
      modulate the direction of AM activation. The CL technique is thought to be useful
      to evaluate changes in AM activity. In this study, the results suggest that,
      using the high-risk model of allergic diseases, NO2 exposure from the weanling
      period has stronger effects on AM activity.

PMID- 16791822
TI  - An assay for inorganic mercury(II) based on its post-catalytic enhancement effect
      on the potassium permanganate-luminol system.
AB  - A strong chemiluminescence (CL) response is observed when potassium permanganate
      solution is injected into basic luminol solution. When the CL reaction
      terminates, subsequent injection of Hg2+ solution into the reaction mixture
      results in a new CL reaction. Based on the post-catalytic enhancement effect of
      Hg2+ on the potassium permanganate-luminol system in basic media, a fast and
      simple CL-coupled flow injection analysis for the determination of Hg2+ was
      developed. In optimum conditions, CL intensity is proportional to Hg2+
      concentration over the range 1.0 x 10(-8)-1.0 x 10(-5) g/mL, with a detection
      limit of 2.0 x 10(-9) g/mL. The relative standard deviation (RSD) is 3.6% for 1.0
      x 10(-7) g/mL Hg2+ (n = 11). After pretreatment with sulphydryl cotton fibre,
      environmental water samples were analysed by the proposed method for total
      mercury determination with satisfactory results. The results were in good
      agreement with those given by hydride generation-cold vapour atomic absorption
      spectrometry (HG-CVAAS).

PMID- 16791823
TI  - Efficient extraction of proteins from woody plant samples for two-dimensional
      electrophoresis.
AB  - Protein extraction from plant samples is usually challenging due to the low
      protein content and high level of contaminants. Therefore, the 2-DE pattern
      resolution is strongly influenced by the procedure of sample preparation.
      Efficient solubilization of proteins strictly depends on the chaotrope and
      detergent in the extraction buffer. Despite the large number of detergents that
      have been developed for the use in protein extraction and IEF, there is no single
      compound able to efficiently extract proteins from any source. Hence,
      optimization has to be performed for each type of sample. We tested several
      chaotrope/detergent combinations to achieve optimal solubilization and separation
      of proteins from Norway spruce [Picea abies (L.) H. Karst.] needles and European
      beech (Fagus sylvatica L.) leaves and roots. The same chaotrope mixture (7 M
      urea, 2 M thiourea) was found to be suitable for the extraction and separation of
      proteins from all samples. Nonetheless, the efficiency of the surfactants tested
      varied between samples so that optimal extraction and separation was achieved
      with different detergents or combination of detergents for each sample. The 2-DE
      separation of spruce needle proteins was optimal in a mixture of two zwitterionic
      detergents (2% CHAPS and 2% decyl dimethylammonio propanesulfonate). Beech
      proteins were best separated in buffers containing sugar-based detergents (2% n
      octyl beta-D-glucopiranoside in the case of leaf samples and 2% dodecyl maltoside
      for the root samples). IEF was performed in buffers with the same composition as
      the extraction buffer except for the root proteins that were better focused in a
      buffer containing 2% CHAPS.

PMID- 16791824
TI  - Proteome analysis of Schizosaccharomyces pombe by two-dimensional gel
      electrophoresis and mass spectrometry.
AB  - The fission yeast Schizosaccharomyces pombe (S. pombe) is a unicellular eukaryote
      and contains many genes and regulatory mechanisms that are close to those of
      mammals. In this study, we performed a global proteomic analysis of the fission
      yeast S. pombe wild type h(-S) L 972 proteome. More than 1,500 protein spots were
      visualized on silver stained 2-D gels in the 3-10 pI range with a high resolution
      and high reproducibility. Protein identification was carried out by MALDI-TOF-MS
      and/or nanoLC-MS/MS. Advantage of the complementarity of these two MS approaches
      was used to enhance the identification quality. So far, 364 proteins
      (representing 157 different proteins) have been identified. We report here the
      identification of 117 new proteins on our 2-D reference map of this yeast
      compared to the first reference map. Of these identified proteins, 40.1% were
      involved in metabolism. The present work provides a very useful tool for all
      studies relying on S. pombe as a model organism and is a considerable complement
      to the first reference map of S. pombe published recently by Sun and coworkers
      (Sun, N., Jang, J., Lee, S., Kim, S. et al.., Proteomics 2005, 5, 1574-1579).

PMID- 16791825
TI  - Myosin binding protein C is differentially phosphorylated upon myocardial
      stunning in canine and rat hearts-- evidence for novel phosphorylation sites.
AB  - Myocardial stunning is the transient cardiac dysfunction that follows brief
      episodes of ischemia and reperfusion without associated myocardial necrosis.
      Currently, there is limited knowledge about its cellular and biochemical
      mechanisms. In order to better understand the underlying mechanisms of
      contractile dysfunction associated with the stunning, comprehensive proteomic
      studies using 2-D DIGE were performed using a regional stunning model in canine
      heart. Cardiac myosin binding protein C (cMyBP-C), a regulatory myofilament
      protein associated with the thick filament, and nebulette, a thin filament
      associated protein, were differentially expressed. Phosphoprotein specific
      staining indicated both protein changes were due to phosphorylation. Subsequent
      phosphorylation mapping of canine cMyBP-C using IMAC and MS/MS identified five
      phosphorylation sites, including three novel sites. In order to further evaluate
      this finding in a different model, cMyBP-C phosphorylation was examined in a rat
      model of global stunning. In the rat model, stunning was associated with
      increased phosphorylation of cMyBP-C at a critical calcium/calmodulin-dependent
      kinase II site, and the increased phosphorylation was largely inhibited when
      stunning was prevented by either ischemic preconditioning or reperfusion in the
      presence of low-calcium buffer. These data indicate cMyBP-C phosphorylation plays
      an important role in myocardial stunning.

PMID- 16791826
TI  - Recent progresses in the application of machine learning approach for predicting
      protein functional class independent of sequence similarity.
AB  - Protein sequence contains clues to its function. Functional prediction from
      sequence presents a challenge particularly for proteins that have low or no
      sequence similarity to proteins of known function. Recently, machine learning
      methods have been explored for predicting functional class of proteins from
      sequence-derived properties independent of sequence similarity, which showed
      promising potential for low- and non-homologous proteins. These methods can thus
      be explored as potential tools to complement alignment- and clustering-based
      methods for predicting protein function. This article reviews the strategies,
      current progresses, and underlying difficulties in using machine learning methods
      for predicting the functional class of proteins. The relevant software and web
      servers are described. The reported prediction performances in the application of
      these methods are also presented, which need to be interpreted with caution as
      they are dependent on such factors as datasets used and choice of parameters.

PMID- 16791827
TI  - Cystic fibrosis enters the proteomics scene: new answers to old questions.
AB  - The discovery in 1989 of the gene encoding for the cystic fibrosis transmembrane
      conductance regulator (CFTR) and its mutation as the primary cause of cystic
      fibrosis (CF), generated an optimistic reaction with respect to the development
      of potential therapies. This extraordinary milestone, however, represented only
      the initial key step in a long path. Many of the mechanisms that govern the
      pathogenesis of CF, the most commonly inherited lethal pulmonary disorder in
      Caucasians, remain even today unknown. As a continuation to genomic research,
      proteomics now offers the unique advantage to examine global alterations in the
      protein expression patterns of CF cells and tissues. The systematic use of this
      approach will probably provide new insights into the cellular mechanisms involved
      in CF dysfunctions, and should ultimately result in the finding of new prognostic
      markers, and in the generation of new therapies. In this article we review the
      current status of proteomic research applied to the study of CF, including CFTR
      related interactomics, and evaluate the potential of these technologies for
      future investigations.

PMID- 16791828
TI  - Comparative proteome analysis of changes in the 26S proteasome during oocyte
      maturation in goldfish.
AB  - Proteasomes are large, multi-subunit particles that act as the proteolytic
      machinery for most of the regulated intracellular protein degradation in
      eukaryotic cells. An alteration of proteasome function may be important for the
      regulation of the meiotic cell cycle. To study the change at the subunit level of
      the 26S proteasome during meiotic maturation, we purified 26S proteasomes from
      immature and mature oocytes of goldfish. Two-dimensional polyacrylamide gel
      electrophoresis was used to separate proteins. For differential analysis, whole
      spots of the 26S proteasome from goldfish oocytes were identified by matrix
      assisted laser desorption/ionization-time of flight mass spectrometry and
      database analysis. Four spots that were different (only detected in mature oocyte
      265 proteasomes and not in immature ones) and four protein spots that were up- or
      down-regulated were identified unambiguously. The mature-specific spots were not
      26S proteasome components but rather their interacting proteins, and were
      identified as chaperonin-containing TCP-1 subunits and myosin light chain. Minor
      spots of three subunits of the 20S core particle and one of the 19S regulatory
      particle showed meiotic cell cycle-dependent changes. These results demonstrate
      that modifications of proteasomal subunits and cell cycle phase-dependent
      interactions of proteins with proteasomes occur during oocyte maturation in
      goldfish.

PMID- 16791829
TI  - Phosphoproteomics strategies for the functional analysis of signal transduction.
AB  - Protein phosphorylation is a key regulatory mechanism of cellular signalling
      processes. The analysis of phosphorylated proteins and the characterisation of
      phosphorylation sites under different biological conditions are some of the most
      challenging tasks in current proteomics research. Reduction of the sample
      complexity is one major step for the analysis of low-abundance kinase substrates,
      which can be achieved by various subcellular fractionation techniques. One
      strategy is the enrichment of phosphorylated proteins or peptides by
      immunoprecipitation or chromatography, e.g. immobilised metal affinity
      chromatography, prior to analysis. 2-DE gels are powerful tools for the analysis
      of phosphoproteins when combined with new multiplexing techniques like DIGE,
      phosphospecific stains, autoradiography or immunoblotting. In addition, several
      gel-free methods combining chromatography with highly sensitive MS have been
      successfully applied for the analysis of complex phosphoproteomes. Recently
      developed approaches like KESTREL or 'chemical genetics' and also protein
      microarrays offer new possibilities for the identification of specific kinase
      targets. This review summarises various strategies for the analyses of
      phosphoproteins with a special focus on the identification of novel kinase
      substrates.

PMID- 16791830
TI  - Proteomic analysis of antigens from Leishmania infantum promastigotes.
AB  - Leishmaniasis is a zoonotic disease caused by the species of the genus
      Leishmania, flagellated protozoa that multiply inside mammalian macrophages and
      are transmitted by the bite of the sandfly. The disease is widespread and due to
      the lack of fully effective treatment and vaccination the search for new drugs
      and immune targets is needed. Proteomics seems to be a suitable strategy because
      the annotated sequenced genome of L. major is available. Here, we present a high
      resolution proteome for L. infantum promastigotes comprising of around 700 spots.
      Western blot with rabbit hyperimmune serum raised against L. infantum
      promastiogote extracts and further analysis by MALDI-TOF and MALDI-TOF/TOF MS
      allowed the identification of various relevant functional antigenic proteins.
      Major antigenic proteins were identified as propionil carboxilasa, ATPase beta
      subunit, transketolase, proteasome subunit, succinyl-diaminopimelate
      desuccinylase, a probable tubulin alpha chain, the full-size heat shock protein
      70, and several proteins of unknown function. In addition, one enzyme from the
      ergosterol biosynthesis pathway (adrenodoxin reductase) and the structural
      paraflagellar rod protein 3 (PAR3) were found among non-antigenic proteins. This
      study corroborates the usefulness of proteomics in identifying new proteins with
      crucial biological functions in Leishmania parasites.

PMID- 16791831
TI  - Mass spectrometry-based proteomics for the detection of plant pathogens.
AB  - Plant diseases caused by fungi, oomycetes, viruses, and bacteria are devastating
      both to the economy and to the food supply of a nation. Therefore, the
      development of new, rapid methods to identify these pathogens is a highly
      important area of research that is of international concern. MS-based proteomics
      has become a powerful and increasingly popular approach to not only identify
      these pathogens, but also to better understand their biology. However, there is a
      distinction between identifying a pathogen protein and identifying a pathogen
      based upon the detection of one of its proteins and this must be considered
      before the general application of MS for plant pathogen detection is made. There
      has been a recent push in the proteomics community to make data from large-scale
      proteomics experiments publicly available in the form of a centralized
      repository. Such a resource could enable the use of MS as a universal plant
      pathogen detection technology.

PMID- 16791832
TI  - Proteomic analysis of Agrobacterium tumefaciens response to the Vir gene inducer
      acetosyringone.
AB  - Agrobacterium tumefaciens causes crown gall disease in a wide range of plants by
      transforming plants through the transfer and integration of its transferred DNA
      (T-DNA) into the host genome. In the present study, we used two-dimensional gel
      electrophoresis to examine the protein expression profiles of A. tumefaciens in
      response to the phenolic compound acetosyringone (AS), a known plant-released
      virulence (vir) gene inducer. Using mass spectrometry, we identified 11 proteins
      consisting of 9 known AS-induced Vir proteins and 2 newly discovered AS-induced
      proteins, an unknown protein Y4mC (Atu6162) and a small heat shock protein HspL
      (Atu3887). Further expression analysis revealed that the AS-induced expression of
      Y4mC and HspL is regulated by the VirA/VirG two-component system. This report
      presents the first proteomics study successfully identifying both known and new
      AS-induced proteins that are implicated in Agrobacterium virulence.

PMID- 16791833
TI  - Chemiluminescence flow-injection analysis of beta-lactam antibiotics using the
      luminol-permanganate reaction.
AB  - A new flow injection chemiluminescence (CL) method has been developed for the
      determination of six beta-lactam antibiotics, including amoxicillin, cefadroxil,
      cefoperazone sodium, cefazolin sodium, cefradine and ceftriaxone sodium. When the
      antibiotic was injected into a stream of KMnO4 with alkaline luminol, a strong CL
      signal was produced. The method allows the measurements of 0.1-50.0 mg/L
      amoxicillin, 0.1-80.0 mg/L cefadroxil, 1.0-30.0 mg/L cefoperazone sodium, 1.0
      30.0 mg/L cefazolin sodium, 3.0-50.0 mg/L cefradine and 3.0-50.0 mg/L ceftriaxone
      sodium. The detection limits are 0.05 mg/L for amoxycillin, 0.05 mg/L for
      cefadroxil, 0.4 mg/L for cefoperazonum sodium, 0.4 mg/L for cefazolin sodium, 0.8
      mg/L for cefradine and 0.8 mg/L for ceftriaxone sodium. The relative standard
      deviations in 11 repeated measurements are 0.6%, 0.8%, 1.5%, 1.2%, 0.4% and 0.3%
      for 3.0 mg/L amoxicillin, 1.0 mg/L cefadroxil, 10.0 mg/L cefoperazone sodium,
      10.0 mg/L cefazolin sodium, 10.0 mg/L cefradine and 10.0 mg/L ceftriaxone sodium,
      respectively. The method was successfully applied to the determination of
      amoxicillin in pharmaceutical preparations. A possible CL reaction mechanism is
      also discussed.

PMID- 16791834
TI  - The preparation of CdTe nanoparticles and CdTe nanoparticle-labelled microspheres
      for biological applications.
AB  - Different sizes of CdTe semiconductor nanoparticles were prepared in aqueous
      solution. These nanoparticles exhibit narrow fluorescence with full width at half
      maximum (FWHM) of 35-45 nm that spans the visible spectrum, and they also have
      high PL quantum yield with high resistance to photodegradation. In addition, CdTe
      quantum dot (QD)-labelled microspheres, comprising polystyrene (PS) cores and
      CdTe/polyelectrolyte (PE) shells, were also prepared by the layer-by-layer
      technique in this paper. The optical properties of the CdTe nanoparticles and
      CdTe-labelled microspheres were investigated by UV-Visible absorption and
      luminescence spectroscopy, and fluorescence microscopy was employed for
      microscopic identification behaviour of the luminescent microspheres.

PMID- 16791835
TI  - Bovine serum albumin displays luciferase-like activity in presence of luciferyl
      adenylate: insights on the origin of protoluciferase activity and bioluminescence
      colours.
AB  - Luciferyl adenylate, the key intermediate in beetle bioluminescence, is produced
      through adenylation of d-luciferin by beetle luciferases and also by mealworm
      luciferase-like enzymes which produce a weak red chemiluminescence. However,
      luciferyl adenylate is only weakly chemiluminescent in water at physiological pH
      and it is unclear how efficient bioluminescence evolved from its weak
      chemiluminescent properties. We found that bovine serum albumin (BSA) and neutral
      detergents enhance luciferyl adenylate chemiluminescence by three orders of
      magnitude, simulating the mealworm luciferase-like enzyme chemiluminescence
      properties. These results suggest that the beetle protoluciferase activity arose
      as an enhanced luciferyl adenylate chemiluminescence in the protein environment
      of the ancestral AMP-ligase. The predominance of luciferyl adenylate
      chemiluminescence in the red region under most conditions suggests that red
      luminescence is a more primitive condition that characterized the original stages
      of protobioluminescence, whereas yellow-green bioluminescence may have evolved
      later through the development of a more structured and hydrophobic active site.

PMID- 16791836
TI  - Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic
      fever.
AB  - Dengue infections are a major cause of morbidity and mortality in the tropical
      and sub-tropical regions of the world. There is no vaccine for dengue and also
      there are no anti-viral drugs to treat the infection. Some patients, typically
      those experiencing a secondary infection with a different dengue serotype, may
      progress from an acute febrile disease to the more severe forms of disease,
      dengue haemorrhagic fever and dengue shock syndrome. Here we discuss the
      significant immunopathological component to severe disease and how T cells,
      cytokines and cross-reactive antibody combine to contribute to the progression to
      dengue haemorrhagic fever. These events are thought to lead to vascular leakage,
      the signature event in dengue haemorrhagic fever, and are addressed in this
      review by incorporating the concept of heterologous T cell immunity. The need for
      effective measures against dengue and dengue-related illness is clear. We propose
      that drugs against dengue virus, or the symptoms of severe dengue disease, are a
      viable goal.

PMID- 16791837
TI  - MicroRNA: a new player in stem cells.
AB  - microRNAs (miRNAs) are an abundant class of endogenous non-protein-coding small
      RNAs, which negatively regulate gene expression at the posttranscriptional level
      in many developmental and metabolic processes. miRNAs regulate a variety of
      biological processes, including developmental timing, signal transduction, tissue
      differentiation and maintenance, disease, and carcinogenesis. Emerging evidence
      demonstrates that miRNAs also play an essential role in stem cell self-renewal
      and differentiation. Some miRNAs are specifically expressed in stem cells,
      control stem cell self-renewal, and differentiation through negatively regulating
      the expression of certain key genes in stem cells.

PMID- 16791838
TI  - Molecular studies of Varicella zoster virus.
AB  - VZV is a highly cell-associated member of the Herpesviridae family and one of the
      eight herpesviruses to infect humans. The virus is ubiquitous in most populations
      worldwide, primary infection with which causes varicella, more commonly known as
      chickenpox. Characteristic of members of the alphaherpesvirus sub-family, VZV is
      neurotropic and establishes latency in sensory neurones. Reactivation from
      latency, usually during periods of impaired cellular immunity, causes herpes
      zoster (shingles). Despite being one of the most genetically stable human
      herpesviruses, nucleotide alterations in the virus genome have been used to
      classify VZV strains from different geographical regions into distinct clades.
      Such studies have also provided evidence that, despite pre-existing immunity to
      VZV, subclinical reinfection and reactivation of reinfecting strains to cause
      zoster is also occurring. During both primary infection and reactivation, VZV
      infects several PBMC and skin cell lineages. Difficulties in studying the
      pathogenesis of VZV because of its high cell association and narrow host range
      have been overcome through the development of the VZV severe combined
      immunodeficient mouse model carrying human tissue implants. This model has
      provided a valuable tool for studying the importance of individual viral proteins
      during both the complex intracellular replication and assembly of new virions and
      for understanding the underlying mechanism of attenuation of the live varicella
      vaccine. In addition, a rat model has been developed and successfully used to
      uncover which viral proteins are important for both the establishment and
      maintenance of latent VZV infection.

PMID- 16791839
TI  - Semiquantitative multiplex PCR: a useful tool for large rearrangement screening
      and characterization.
AB  - Methods presently employed for detection of large rearrangements have several
      drawbacks, such as the amount of sample and time required, technical difficulty,
      or the probability of false-negative carriers. Using the low-density-lipoprotein
      receptor (LDLR) gene, whose mutations are responsible for familial
      hypercholesterolemia (FH), we have developed a procedure to detect large
      rearrangements in this gene based on semiquantitative PCR, with important
      improvements as compared to previous methods. Our method covers the complete LDLR
      gene and introduces an internal control in the reaction. The procedure
      discriminates the four different large rearrangements (two deletions and two
      insertions) that we have used as positive mutation controls (Valencia-1 to -5).
      All altered exons from each rearrangement are identified. Furthermore, when
      families from probands carrying these large rearrangements (34 members) were
      analyzed, our results agreed with those obtained previously with Southern blot.
      We have also analyzed a sample of 110 unrelated FH probands and the method has
      correctly identified the two different large rearrangements present and
      insertions or deletions as small as 1 bp. In conclusion, the method we present
      allows the identification of large rearrangements affecting exons of the gene,
      including small insertions or deletions or complete gene deletion. In addition,
      it constitutes a first characterization step of rearrangements, and is easy to
      carry out fast, and can be applied to the analysis of any gene.

PMID- 16791841
TI  - MLPA: a rapid, reliable, and sensitive method for detection and analysis of
      abnormalities of 22q.
AB  - In this study, essential test characteristics of the recently described multiplex
      ligation-dependent probe amplification (MLPA) method are presented, using
      chromosome 22 as a model. This novel method allows the relative quantification of
      approximately 40-45 different target DNA sequences in a single reaction. For the
      purpose of this study, MLPA was performed in a blinded manner on a training set
      containing over 50 samples, including typical 22q11.2 deletions, various atypical
      deletions, duplications (trisomy and tetrasomy), and unbalanced translocations.
      All samples in the training set have been previously characterized by
      fluorescence in situ hybridization (FISH) with cosmid or BAC clones and/or
      cytogenetic studies. MLPA findings were consistent with cytogenetic and FISH
      studies, no rearrangement went undetected and repeated tests gave consistent
      results. At a relative change in comparative signal strength of 30% or more,
      sensitivity and specificity values were 0.95 and 0.99, respectively. Given that
      MLPA is likely to be used as an initial screening method, a higher sensitivity,
      at the cost of a lower specificity, was deemed more appropriate. A receiver
      operator characteristic (ROC) curve analysis was performed to calculate the most
      optimal threshold range, with associated sensitivity and specificity values of
      0.99 and 0.97, respectively. Finally, performance of each individual probe was
      analyzed, providing further useful information for the interpretation of MLPA
      results. In conclusion, MLPA has proven to be a highly sensitive and accurate
      tool for detecting copy number changes in the 22q11.2 region, making it a fast
      and economic alternative to currently used methods. The current study provides
      valuable and detailed information on the characteristics of this novel method.

PMID- 16791840
TI  - Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis.
AB  - Ten years ago, the groundwork for the discovery of the genetic basis of chronic
      pancreatitis was laid by linkage analyses of large kindreds with autosomal
      dominant hereditary chronic pancreatitis. Subsequent candidate gene sequencing of
      the 7q35 chromosome region revealed a strong association of the c.365G > A
      (p.R122 H) mutation of the PRSS1 gene encoding cationic trypsinogen with
      hereditary pancreatitis. In the following years, further mutations of this gene
      were discovered in patients with hereditary or idiopathic chronic pancreatitis.
      In vitro the mutations increase autocatalytic conversion of trypsinogen to active
      trypsin and thus probably cause premature, intrapancreatic trypsinogen activation
      in vivo. The clinical presentation is highly variable, but most affected mutation
      carriers have relatively mild disease. In this review, we summarize the current
      knowledge on trypsinogen mutations and their role in pancreatic diseases.

PMID- 16791843
TI  - Pathogenesis of chronic active Epstein-Barr virus infection: is this an
      infectious disease, lymphoproliferative disorder, or immunodeficiency?
AB  - Chronic active Epstein-Barr virus infection (CAEBV) is characterised by chronic
      or recurrent infectious mononucleosis-like symptoms, such as fever,
      hepatosplenomegaly, persistent hepatitis and extensive lymphadenopathy. Patients
      with CAEBV have high viral loads in their peripheral blood and/or an unusual
      pattern of EBV-related antibodies. This disease is rare but severe with high
      morbidity and mortality. Nearly three decades have passed since this disease was
      first identified, and recent advances in technology have increased our
      understanding of CAEBV pathophysiology. There is accumulating evidence that the
      clonal expansion of EBV-infected T or natural killer (NK) cells plays a central
      role in the pathogenesis of CAEBV. However, it remains unclear whether CAEBV is
      truly a monoclonal lymphoproliferative disorder. EBV-infected T or NK cells are
      able to evade the host cellular immune system due to the limited expression of
      viral proteins of reduced antigenicity. Recent studies suggest that infection of
      T or NK cells is a common event during primary EBV infection. A defect or single
      nucleotide polymorphism in host immune-modulating genes may allow for the
      expansion of virus infected cells giving rise to CAEBV. In this review, I
      summarise our current understanding of the pathogenesis of CAEBV and propose a
      model of CAEBV pathogenicity.

PMID- 16791842
TI  - Early caspase-3 activation independent of apoptosis is required for cellular
      function.
AB  - A number of pro-apoptotic stimuli induce the activation of caspase-9, an
      initiator protease that activates executioner caspases, such as caspase-3,
      leading to the development of programmed cell death. Here we demonstrate that
      cell (platelets and pancreatic acinar cells) stimulation with agonists induces a
      bimodal activation of caspase-3. The early caspase-3 activation occurs within 1
      min of stimulation and is independent on caspase-9 or mitochondrial cytochrome c
      release suggesting that is a non-apoptotic event. The ability of agonists to
      induce early activation of caspase-3 is similar to that observed for other
      physiological processes. Activation of caspase-3 by physiological concentrations
      of cellular agonists, including thrombin or CCK-8, is independent of rises in
      cytosolic calcium concentration but requires PKC activation, and is necessary for
      agonist-induced activation of the tyrosine kinases Btk and pp60src and for
      several cellular functions, including store-operated calcium entry, platelet
      aggregation, or pancreatic secretion. Thus, early activation of caspase-3 seems
      to be a non-apoptotic event required for cellular function.

PMID- 16791844
TI  - Bapx1 homeobox gene gain-of-function mice show preaxial polydactyly and activated
      Shh signaling in the developing limb.
AB  - To explore Bapx1 homeobox gene function in embryonic control of development, we
      employed a gain-of-function approach to complement our previous loss-of-function
      mutant analysis. We show that transgenic mice overexpressing Bapx1 are affected
      by skeletal defects including hindlimb preaxial polydactyly and tibial
      hypoplasia. Bapx1 overexpression generates limb anteroposterior patterning
      defects including induction of Shh signaling and ectopic activation of functions
      downstream of Shh signaling into the anterior region of the autopod. Moreover,
      Bapx1 overexpression stimulates formation of limb prechondrogenic condensations.
      We also show that Shh is reciprocally able to activate Bapx1 expression in mouse
      embryos as the orthologous hedgehog (hh) does with the bagpipe/Bapx1 gene in
      Drosophila. Our results indicate that Bapx1 can modulate appendicular skeletal
      formation, that the genetic hierarchy between Shh/hh and Bapx1/bagpipe has been
      conserved during evolution, and that in mouse embryos these two genes can
      influence one another in a genetically reciprocal manner. We conclude that it is
      reasonable to expect overexpression of Bapx1 in certain forms of polydactyly.

PMID- 16791845
TI  - Bladder augmentation for the treatment of chronic tuberculous cystitis. Clinical
      and urodynamic evaluation of 25 patients after long term follow-up.
AB  - AIMS: Clinical and urodynamic evaluation of the late outcome of 25 patients with
      chronic tuberculous cystitis who underwent bladder augmentation. PATIENTS AND
      METHODS: Twenty men and five women with median age of 40 years were evaluated.
      The tubularized ileocecal segment was used in 8 cases, the detubularized sigmoid
      in 13, and the tubularized sigmoid in 4. Patients underwent a postoperative
      clinical and urodynamic evaluation. Miccional diurnal frequency of more than 2 hr
      together with patient satisfaction as assessed by the quality of life question of
      the ICSmaleSF questionnaire was considered a good result. RESULTS: The average
      postoperative follow-up was of 11.1 +/- 9.1 (1 to 36) years. A good result was
      seen in 80% of the patients. Bad results occurred statistically in the cases
      using tubularized sigmoid and in patients with prostatitis. Patients with good
      results showed augmented bladders with normal sensation (P = 0.03) and greater
      capacity (P < 0.01) and compliance (P < 0.01) than did those with bad results.
      There was no statistically significant difference in the frequency of involuntary
      contractions (P = 0.27) but in the good result patients, the contractions started
      with greater bladder filling volume (P = 0.02). CONCLUSIONS: The sigmoid should
      be detubularized but the ileocecal segment may be used in its original
      tubularized form to augment the bladder with chronic tuberculous cystitis.
      Augmented bladder with capacity of more than 250 ml, good compliance, and normal
      sensation are necessary for diurnal frequency of more than 2 hr. The presence of
      involuntary contractions does not lead to a decrease in the diurnal frequency.

PMID- 16791846
TI  - Nodal-related gene Xnr5 is amplified in the Xenopus genome.
AB  - In Xenopus, six nodal-related genes (Xnrs) have been identified to date. We found
      numerous tandem duplications of Xnr5 in the Xenopus laevis and Xenopus tropicalis
      genomes that involve highly conserved copies of coding and regulatory regions.
      The duplicated versions of Xnr5 were expressed in both the superficial and deep
      layer of dorsal endoderm and in the deep layer of ventral endoderm, where the
      initial inducers of mesendoderm formation would be expected to be localized.
      Overexpression of secreted inhibitors of Xnrs led to a substantially enhanced
      transcription of the duplicated Xnr5 genes and Xnr6 in embryos. Therefore, Xnr5
      and Xnr6 have a novel feedback loop to inhibit transcription of Xnr5 and Xnr6.
      These results suggest that the initialization of a strong Xnr5 and Xnr6 signal is
      enabled by the rapid transcription from multiple genes. The novel feedback loop
      may negatively regulate transcription of Xnr5s and Xnr6 to limit overproduction
      of these potent inducers, with the Xnr5/Xnr6 signal then activating positive
      (Xnrs) and negative (Xlefty) loops, which regulate the range of mesodermal
      tissues produced.

PMID- 16791847
TI  - An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A,
      expressed from the Rosa26 locus.
AB  - The means to specifically ablate cells inside of a living organism have recently
      been improved and facilitated by stable mouse lines, carrying conditional
      expression constructs for diphtheria toxin (DT) or diphtheria toxin receptor,
      that could be activated upon Cre-mediated recombination or the application of
      diphtheria toxin, respectively. We have lately described the R26:lacZ/DT-A line
      (Brockschnieder et al., 2004, Mol Cell Biol 24:7636-7642) in which a loxP
      conditional DTA allele was introduced into the ubiquitously expressed Rosa26
      locus. This strain allowed the ablation of a wide spectrum of cell types by
      crossing it to tissue specific Cre lines. Unexpectedly, homozygous (but not
      heterozygous) animals of the R26:lacZ/DT-A line developed some degenerative
      abnormalities in a variety of tissues. The defects were most probably caused by
      leaky expression of small amounts of toxin from the unrecombined lacZ(flox)DT-A
      cassette. Here we show that insertion of an additional transcriptional regulatory
      sequence (bovine growth hormone polyadenylation signal, bpA) following the lacZ
      open reading frame prevented the formation of any defects in homozygous mice. The
      modification did not affect the functionality of the lacZ(flox)DTA allele, as
      exemplified by the complete ablation of oligodendrocytes upon Cre-mediated
      recombination. The novel R26:lacZbpA(flox)DTA line is expected to greatly
      facilitate the reliable generation of cell type ablated mice.

PMID- 16791848
TI  - Stereoselective pharmacokinetics of cetirizine in the guinea pig: role of protein
      binding.
AB  - PURPOSE: To characterize the pharmacokinetics of cetirizine enantiomers in the
      guinea pig including protein binding in both the guinea pig and human plasma.
      METHODS: Plasma concentrations of cetirizine enantiomers in the guinea pig were
      determined using a LC-MS/MS method after a short i.v. infusion (1, 2 and 4 mg/kg)
      of racemic cetirizine. Protein binding was determined using an in vitro
      equilibrium dialysis technique. A pharmacokinetic model was developed using
      NONMEM and the differences in pharmacokinetic parameters of levocetirizine and
      dextrocetirizine were estimated. RESULTS: The plasma concentration time data of
      both the enantiomers were best described by a three-compartment pharmacokinetics
      model. The clearance (CL) of levocetirizine and dextrocetirizine was 1.2 and 2.7
      ml/min, respectively, and the volume of distribution at steady state (Vss) was
      457 ml and 996 ml, respectively. The fraction unbound (fu) in guinea pig plasma
      for levocetirizine and dextrocetirizine was 7-10% and 16-21% while in human
      plasma, it was 8% and 12%, respectively. The factor describing the difference in
      the pharmacokinetic parameters of the cetirizine enantiomers was estimated to be
      2.26. CONCLUSIONS: Cetirizine pharmacokinetics is stereoselective in the guinea
      pig. For levocetirizine, fu, CL and Vss were half those of dextrocetirizine,
      indicating that protein binding is an important factor affecting the
      pharmacokinetics of cetirizine. The effect of protein binding on the
      pharmacokinetics of the cetirizine enantiomers could be extrapolated to humans.

PMID- 16791849
TI  - Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in
      Marfan syndrome-related disorders.
AB  - Very recently, heterozygous mutations in the genes encoding transforming growth
      factor beta receptors I (TGFBR1) and II (TGFBR2) have been reported in Loeys
      Dietz aortic aneurysm syndrome (LDS). In addition, dominant TGFBR2 mutations have
      been identified in Marfan syndrome type 2 (MFS2) and familial thoracic aortic
      aneurysms and dissections (TAAD). In the past, mutations of these genes were
      associated with atherosclerosis and several human cancers. Here, we report a
      total of nine novel and one known heterozygous sequence variants in the TGFBR1
      and TGFBR2 genes in nine of 70 unrelated individuals with MFS-like phenotypes who
      previously tested negative for mutations in the gene encoding the extracellular
      matrix protein fibrillin-1 (FBN1). To assess the pathogenic impact of these
      sequence variants, in silico analyses were performed by the PolyPhen, SIFT, and
      Fold-X algorithms and by means of a 3D homology model of the TGFBR2 kinase
      domain. Our results showed that in all but one of the patients the pathogenic
      effect of at least one sequence variant is highly probable (c.722C > T, c.799A >
      C, and c.1460G > A in TGFBR1 and c.773T > G, c.1106G > T, c.1159G > A, c.1181G >
      A, and c.1561T > C in TGFBR2). These deleterious alleles occurred de novo or
      segregated with the disease in the families, indicating a causative association
      between the sequence variants and clinical phenotypes. Since TGFBR2 mutations
      found in patients with MFS-related disorders cannot be distinguished from
      heterozygous TGFBR2 mutations reported in tumor samples, we emphasize the
      importance of segregation analysis in affected families. In order to be able to
      find the mutation that is indeed responsible for a MFS-related phenotype, we also
      propose that genetic testing for sequence alterations in TGFBR1 and TGFBR2 should
      be complemented by mutation screening of the FBN1 gene.

PMID- 16791851
TI  - What is recovery in adolescent anorexia nervosa?
AB  - OBJECTIVE: The principal aim of this study is to describe the types of problems
      faced in defining recovery from anorexia nervosa (AN) as well as to illustrate
      the magnitude that various definitions have on recovery rates for AN. METHOD:
      Comparative rates of recovery from AN using a range of definitions (percent ideal
      body weight, psychological recovery, and combinations of these variables) were
      calculated using long-term outcome data from a study of adolescents treated for
      AN. In addition, a Kaplan-Meier survival analysis was used to model recovery over
      the long-term follow-up period. RESULTS: Recovery rates varied highly, depending
      on the definition used, from 57.1% to 94.4%. Using survival analysis, the mean
      time to remission for weight (>85% ideal body weight) was 11.3 months,
      significantly shorter than for Eating Disorder Examination score recovery at 22.6
      months (log rank = 16.1, p = 0.0001). CONCLUSION: Agreement of definitions of
      recovery may be dependent on specific goals of a particular study or treatment;
      however, in order to compare and contrast categorical outcomes, a consistent
      definition of recovery is needed in the literature. Both weight and psychological
      symptoms appear to be important in a definition of recovery.

PMID- 16791850
TI  - Scribble associates with two polarity proteins, Lgl2 and Vangl2, via distinct
      molecular domains.
AB  - Scribble (Scrib) is a large multi-domain cytoplasmic protein that was first
      identified through its requirement for the establishment of epithelial polarity.
      We tested the hypotheses that Scrib asssociates with the basolateral membrane via
      multiple domains, binds specific protein partners, and is part of a multimeric
      complex. We generated a series of EGFP-tagged Scrib fusion proteins and examined
      their membrane localizations in two types of polarized mammalian epithelial cells
      using biochemical and morphological approaches. We found that Scrib's Leucine
      rich-repeat (LRR) and PDS-95/Discs Large/ZO-1 (PDZ) domains independently
      associate with the plasma membrane in both cell types. We identified multiple
      large Scrib complexes, demonstrated that Scrib and the cytoplasmic protein Lethal
      giant larvae2 (Lgl2) co-IP and that this association occurs via Scrib's LRR
      domain. Further, this report demonstrates that the membrane protein Vangl2 binds
      selectively to specific PDZ domains in Scrib. Our identification of Scrib's
      associations highlights its function in multiple biologic pathways and sets the
      stage for future identification of more proteins that must interact with Scrib's
      remaining domains. J. Cell. Biochem. 99: 647-664, 2006. (c) 2006 Wiley-Liss, Inc.

PMID- 16791852
TI  - Time trends in the incidence of eating disorders: a primary care study in the
      Netherlands.
AB  - OBJECTIVE: This Dutch epidemiological study used primary care-based data to
      examine changes in the incidence of eating disorders in the 1990s compared to the
      1980s. METHOD: A nationwide network of general practitioners, serving a
      representative sample of the total Dutch population, recorded newly diagnosed
      patients with anorexia nervosa (AN) and bulimia nervosa (BN) in their practices
      during 1985-1989 and 1995-1999. RESULTS: The overall incidence of AN was stable
      (from 7.4 to 7.7 per 100,000). However, the incidence among 15-19-year-old
      females increased significantly (from 56.4 to 109.2 per 100,000). The incidence
      rate of BN decreased nonsignificantly from 8.6 to 6.1 per 100,000. CONCLUSION:
      The time trend of an increasing AN incidence among the high risk group continued
      to the end of the past century. The BN incidence did not rise as was expected.

PMID- 16791853
TI  - New role for spinal Stargazin in alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor-mediated pain sensitization after inflammation.
AB  - Considerable evidence has demonstrated that alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor blockade has an antinociceptive effect on
      inflammatory pain. Stargazin (STG) is the first transmembrane protein known to
      associate with AMPA receptors and regulate their synaptic targeting. However, it
      is not known whether STG is involved in inflammatory pain processing by
      regulating AMPA receptor function. In the present study, we investigated the
      effect of knockdown of spinal STG on AMPA receptor-mediated pain sensitization
      after inflammation. Antisense technology was employed to knock down STG
      expression in the spinal cord. We show that STG was expressed and interacted with
      AMPA receptor subunit GluR2 in the spinal cord. Intrathecally injected STG
      antisense oligodeoxyribonucleotide (ODN) specifically decreased STG expression in
      the lumbar spinal cord and dose dependently inhibited formalin-induced
      inflammatory pain in the second phase. More important was our finding for the
      first time that this specific STG antisense ODN diminished AMPA (0.1 mug)
      enhanced formalin pain and lost its effect if pretreated with AMPA receptor
      antagonist CNQX. Our results demonstrate a new role for STG in central
      sensitization of inflammatory pain by interacting with AMPA receptors in the
      spinal cord.

PMID- 16791854
TI  - Involvement of the nitric oxide/protein kinase G pathway in polychlorinated
      biphenyl-induced cell death in SH-SY 5Y neuroblastoma cells.
AB  - Polychlorinated biphenyls (PCB) are persistent environmental contaminants whose
      chronic exposure can affect nervous system development and function. The cellular
      and molecular mechanisms underlying neuronal damage are not yet clear. In the
      present study, we investigated whether nitric oxide (NO) could be involved in
      aroclor 1254 (A1254; a PCB mixture)-induced cytotoxicity in SH-SY5Y human
      neuroblastoma cells. Prolonged exposure (24 hr) to A1254 (10-100 microg/ml)
      caused a dose-dependent reduction of cell viability that was attenuated in the
      presence of a calcium entry blocker, gadolinum (Gd(3+)) at 10 microM, a
      concentration able to block voltage-sensitive calcium channels. In addition,
      A1254 caused an increase of cytosolic calcium that was dependent on extracellular
      calcium, as measured by fura-2 videomicroscopy. A1254-induced calcium rise may
      stimulate NO production through an activation of neuronal NOS (nNOS). Indeed, the
      concomitant addition of the selective nNOS inhibitor N(omega)-propyl-L-arginine
      (NPLA) and A1254 prevented cell injury, suggesting that NO production plays a
      major role in A1254-evoked cell injury. Furthermore, the exposure (14 hr) to
      A1254 (30 microg/ml) produced an up-regulation of the expression of beta isoform
      of nNOS. This up-regulation was calcium dependent and was accompanied by an
      enhancement of NO production as demonstrated by an increase of nitrite formation.
      Moreover, A1254-induced cell injury was prevented when KT 5823, a selective
      cGMP/PKG inhibitor, was added concomitantly to 30 microg/ml A1254. These results
      suggest that PCB-induced cell death in neuroblastoma cells is mediated by an
      activation of the cGMP/PKG pathway triggered by NO production.

PMID- 16791855
TI  - Downregulation of the RECK-tumor and metastasis suppressor gene in glioma
      invasiveness.
AB  - Invasive behavior is the pathological hallmark of malignant gliomas, being
      responsible for the failure of surgery, radiation, and chemotherapy. Matrix
      metalloproteinases (MMPs) are essential for proper ECM remodeling and invasion.
      The tumor and metastasis suppressor RECK protein regulates at least three members
      of the MMPs family: MMP-2, MMP-9, and MT1-MMP. In order to mimic the in vivo
      invasion process, A172 and T98G, respectively, non-invasive and invasive human
      glioblastoma cell lines, were cultured onto uncoated (control) or type I collagen
      gel-coated surface, and maintained for up to 7 days to allow establishment of the
      invasive process. We show that the collagen substrate causes decreased growth
      rates and morphological alterations correlated with the invasive phenotype.
      Electronic transmission microscopy of T98G cells revealed membrane invaginations
      resembling podosomes, which are typically found in cells in the process of
      crossing tissue boundaries, since they constitute sites of ECM degradation. Real
      time PCR revealed higher RECK mRNA expression in A172 cells, when compared to
      T98G cells and, also, in samples obtained from cultures where the invasive
      process was fully established. Interestingly, the collagen substrate increases
      RECK expression in A172 cells and the same tendency is displayed by T98G cells.
      MMPs-2 and -9 displayed higher levels of expression and activity in T98G cells,
      and their activities are also upregulated by collagen. Therefore, we suggest
      that: (1) RECK downregulation is critical for the invasiveness process displayed
      by T98G cells; (2) type 1 collagen could be employed to modulate RECK expression
      in glioblastoma cell lines. Since a positive correlation between RECK expression
      and patients survival has been noted in several types of tumors, our results may
      contribute to elucidate the complex mechanisms of malignant gliomas invasiveness.

PMID- 16791856
TI  - Etiology of hypercholesterolemia in patients with anorexia nervosa.
AB  - OBJECTIVE: Hypercholesterolemia is common in patients with anorexia nervosa (AN)
      despite emaciation. The objective of this study was to clarify the mechanism of
      hypercholesterolemia in AN. METHOD: We measured serum lipids in 39 patients with
      AN and analyzed serum lipid profiles in the 24 patients in comparison with five
      age-matched controls. RESULTS: Mean serum levels of total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), ketone bodies, apolipoprotein (apo)-A1, B, C2, C3, E, and cholesterol
      ester transfer protein (CETP) activity were significantly higher in patients with
      AN than in controls. No significant difference in serum free fatty acid (FFA)
      levels was observed between patients with AN and controls. CETP was accelerated
      in patients with AN with hypercholesterolemia. No correlation was apparent
      between serum levels of cholesterol and thyroid hormones. CONCLUSION: Serum
      levels of cholesterol, CETP, and apolipoproteins decreased after weight gain,
      indicating that cholesterol metabolism is accelerated in patients with AN with
      normal serum levels of FFA.

PMID- 16791857
TI  - Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of
      two ultrasmall superparamagnetic particles of iron oxide.
AB  - PURPOSE: To evaluate a new ultrasmall superparamagnetic particles of iron oxide
      (USPIO) compound, ferumoxytol, as a marker of macrophage activity in
      atherosclerotic plaques and to compare it to ferumoxtran-10. MATERIALS AND
      METHODS: Ten mature heritable hyperlipidemic (WHHL) female Watanabe rabbits
      served as the animal model for atherosclerosis, four coeval female New Zealand
      White (NZW) rabbits were the control group. Five WHHL and two NZW received a
      single intravenous injection (250 micromol/kg) of either ferumoxtran-10 or
      ferumoxytol and were subjected to daily MR examinations on a 1.5T whole body
      scanner for the next five days. Development of signal intensity changes and
      susceptibility effects was assessed. Statistical analysis was based on a
      nonparametric Wilcoxon-Mann-Whitney-U test by using a P value at the 0.05
      significance level. On day 5, the rabbits were sacrificed and the aorta was
      referred to histopathology, distribution of iron particles in the vessel wall was
      analyzed. RESULTS: MRI was feasible in all animals. Three days after injection of
      ferumoxytol the highest luminal signal intensity measurements were observed in
      the ferumoxytol group; the highest measurements were five days after injection in
      the ferumoxtran-10 group (P < 0.05). In the WHHL, susceptibility effects
      presented as homogeneous dark lines parallel to the aortic wall after ferumoxytol
      and spotted areas void of signal after ferumoxtran-10. None of these findings
      were observed in the NZW control groups. CONCLUSION: Ferumoxtran-10 and
      ferumoxytol at a respective dose of 250 mumol/kg appear well suited for
      atherosclerotic plaque detection with MRI in experimental atherosclerosis.
      Ferumoxytol warrants further analysis in humans.

PMID- 16791858
TI  - Variable MR findings in ovarian functional hemorrhagic cysts.
AB  - PURPOSE: To describe the magnetic resonance (MR) findings in ovarian functional
      hemorrhagic cysts (FHC). MATERIALS AND METHODS: A total of 21 patients with 22
      FHC, proven by follow-up ultrasound (US) in 11 women and surgery in 10 women, had
      US and MR examinations within 24 hours. The study was limited to cysts with
      obvious an echogenic pattern. All patients had T2-weighted fast spin echo (FSE),
      T1-weighted spin echo (SE), and T1-weighted SE fat-suppressed sequences. RESULTS:
      Four cysts (18%) were hypointense on T1-weighted-images without and with fat
      suppression, and hyperintense on T2-weighted-images. Five cysts (23%) were
      hypointense on T1-weighted images without and with fat suppression but
      heterogenous on T2-weighted images. Five cysts (23%) were hypointense on T1
      weighted images but showed intermediate signal intensity on T1-weighted fat
      suppression images and heterogenous signal intensity on T2-weighted images. Two
      cysts (9%) were entirely intermediate on T1-weighted images. Five cysts (23%)
      displayed high signal intensity occupying less than 30% of the cystic content on
      T1-weighted images and one cyst (5%) displayed high signal intensity occupying
      more than 30% of the cystic content. CONCLUSION: Despite an obvious echogenic
      pattern on US, 64% of FHC were hypointense on T1-weighted images and 18% were
      also hyperintense on T2-weighted images. Only 36% demonstrated intermediate or
      high signal intensity on T1-weighted images.

PMID- 16791859
TI  - Limits on activation-induced temperature and metabolic changes in the human
      primary visual cortex.
AB  - Changes in cerebral blood flow (CBF) and metabolism are now widely used to map
      and quantify neural activity, although the underlying mechanism for these changes
      is still incompletely understood. Magnetic resonance spectroscopy (MRS) at 3T,
      synchronized with a 32-s block design visual stimulation paradigm, was employed
      to investigate activation-induced changes in temperature and metabolism in the
      human primary visual cortex. A marginally significant increase in the local
      temperature of the visual cortex was found (0.1 degrees C, P = 0.09), excluding
      the possibility of a temperature decrease (95% confidence interval (CI) = 0.0-0.2
      degrees C), which was previously suggested. A comparison with models of thermal
      equilibrium in the presence of blood flow suggests that an increase in heat
      production during activation, greater than or at least equal to that produced by
      the complete oxidative metabolism of the elevated glucose (Glc) utilization
      accompanying activation, would be required to offset the cooling effects of the
      increased blood flow. The total pools of glutamate (Glu), glutamine (Gln), myo
      Inositol (mI), N-acetylaspartate (NAA), choline (Cho), and lactate (Lac) were not
      significantly affected by activation. Limits on Lac concentration changes were
      too weak to constrain theories of the metabolic use of elevated Glc consumption
      during stimulation, and emphasize the challenges of measuring even large Lac
      changes accompanying stimulation.

PMID- 16791860
TI  - Decomposed direct matrix inversion for fast non-cartesian SENSE reconstructions.
AB  - A new k-space direct matrix inversion (DMI) method is proposed here to accelerate
      non-Cartesian SENSE reconstructions. In this method a global k-space matrix
      equation is established on basic MRI principles, and the inverse of the global
      encoding matrix is found from a set of local matrix equations by taking advantage
      of the small extension of k-space coil maps. The DMI algorithm's efficiency is
      achieved by reloading the precalculated global inverse when the coil maps and
      trajectories remain unchanged, such as in dynamic studies. Phantom and human
      subject experiments were performed on a 1.5T scanner with a standard four-channel
      phased-array cardiac coil. Interleaved spiral trajectories were used to collect
      fully sampled and undersampled 3D raw data. The equivalence of the global k-space
      matrix equation to its image-space version, was verified via conjugate gradient
      (CG) iterative algorithms on a 2x undersampled phantom and numerical-model data
      sets. When applied to the 2x undersampled phantom and human-subject raw data, the
      decomposed DMI method produced images with small errors (< or = 3.9%) relative to
      the reference images obtained from the fully-sampled data, at a rate of 2 s per
      slice (excluding 4 min for precalculating the global inverse at an image size of
      256 x 256). The DMI method may be useful for noise evaluations in parallel coil
      designs, dynamic MRI, and 3D sodium MRI with fixed coils and trajectories.

PMID- 16791861
TI  - Time dependence of 3He diffusion in the human lung: measurement in the long-time
      regime using stimulated echoes.
AB  - A stimulated-echo-based technique was developed to measure the long-time-scale
      apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breath
      hold acquisition. Computer simulations were used to evaluate the performance of
      the technique and guide the selection of appropriate parameter values for
      obtaining accurate ADC values. The technique was used in 10 healthy subjects and
      two subjects with chronic obstructive pulmonary disease (COPD) to measure the
      global ADC for diffusion times between a few tenths of a second and several
      seconds, and to acquire spatial maps of the ADC for a diffusion time of 1.5 s.
      The reproducibility of the technique and its sensitivity to the direction of
      diffusion sensitization were also investigated. In healthy subjects, global ADC
      values decreased by severalfold over the range of diffusion times measured (mean
      values = 0.039 and 0.023 cm2/s at diffusion times of 0.61 and 1.54 s,
      respectively). ADC maps were generally uniform, with mean values similar to the
      corresponding global values. For the two COPD subjects, global ADC values were
      substantially greater than those of every healthy subject at all diffusion times
      measured. In addition, regional elevations of ADC values were far more
      conspicuous on long-time-scale ADC maps than on short-time-scale ADC maps.

PMID- 16791862
TI  - 3D fluoroscopy with real-time 3D non-cartesian phased-array contrast-enhanced
      MRA.
AB  - For optimized CE-MRA of the chest and abdomen, the scan time and breath-hold must
      be coordinated with the arrival of contrast. A 3D fluoroscopy system is
      demonstrated that performs real-time 3D projection reconstruction acquisition,
      reconstruction, and visualization using only the standard scanner hardware and
      operator console workstation. Unlike 2D fluorotriggering techniques, no
      specification of a monitoring slab or careful placement of the imaging volume is
      required. 3DPR data are acquired continuously throughout the examination using an
      eight-channel receiver and 1 s interleaved subframes. The data are reconstructed
      using 1 s segments for real-time monitoring with 0.8-cm isotropic spatial
      resolution over the entire torso, allowing full-volume axial, coronal, and
      sagittal MIPs to be displayed simultaneously with minimal latency. The system
      later uses the same scan data to generate high-spatial-resolution time-resolved
      sequences of the breath-hold interval. The 3D fluoroscopy system was validated on
      phantoms and human volunteers.

PMID- 16791863
TI  - Improvement of quantification of myocardial first-pass perfusion mapping: a
      temporal and spatial wavelet denoising method.
AB  - Mapping of myocardial blood flow (MBF) with first-pass perfusion imaging is
      becoming an important tool in the study of coronary artery disease. In this study
      a wavelet-based denoising method was developed to improve the accuracy of pixel
      by-pixel MBF maps. We performed an in vivo study in five stenotic dogs with 70%
      stenosis in the left coronary arteries. First-pass perfusion imaging sessions
      were performed by administering the intravascular contrast agent Gadomer at rest
      and during dipyridamole-induced vasodilation. Color microspheres (MS) were
      injected into the dogs to measure MBF at the same time. After denoising was
      performed, the signal-to-noise ratio (SNR) of the first-pass perfusion image
      improved by approximately 180%, whereas spatial variation of MBF maps decreased
      38%. It was also found that the correlation of MBFs measured by MRI with the MS
      method indicates a significant improvement with the denoising method (R2
      increased from 0.24 to 0.78, P < .001). This suggests that the wavelet denoising
      method may be an effective way to increase the accuracy of pixel-by-pixel MBF
      quantification and reduce spatial variation, and may be applicable to other forms
      of noise-sensitive image analysis.

PMID- 16791864
TI  - In vivo diffusion tensor imaging of the human optic nerve: pilot study in normal
      controls.
AB  - Diffusion tensor imaging (DTI) of the optic nerve (ON) was acquired in normal
      controls using zonally oblique multislice (ZOOM) DTI, which excites a small field
      of view (FOV) using a fast sequence with a shortened EPI echo train. This
      combines the benefit of low sensitivity to motion (due to the single-shot
      acquisition used), with the additional advantage of reduced sensitivity to
      magnetic field susceptibility artifacts. Reducing the bright signal from the fat
      and cerebrospinal fluid (CSF) surrounding the nerve are key requirements for the
      success of the presented method. Measurements of mean diffusivity (MD) and
      fractional anisotropy (FA) indices were made in a coronal section of the middle
      portion of the optic nerve (ON) in the right (rON) and left (lON) ONs. The
      average values across 10 healthy volunteers were FArON = 0.64 +/- 0.09 and FAlON
      = 0.57 +/- 0.10, and MDrON = (1173 +/- 227) x 10(-6) mm2 s(-1) and MDlON = (1266
      +/- 170) x 10(-6) mm2 s(-1). Measurements of the principal eigenvalue of the DT
      and its orthogonal component were also in agreement with those expected from a
      highly directional structural organization.

PMID- 16791866
TI  - A novel approach for in-process monitoring and managing cross-contamination in a
      high-throughput high-performance liquid chromatography assay with tandem mass
      spectrometric detection.
AB  - Cross-contamination among wells of a high-throughput, high-density assay is a
      risk that cannot be detected or controlled by the performance of calibration
      standards and quality control samples. In the current practice, carryover and
      cross-contamination is detected only when analytes are detected in blank, zero,
      placebo, pre-dose samples, in a low standard or low quality control sample. There
      is no mechanism that allows bioanalytical scientists to determine if cross
      contamination has occurred among other samples. As a result, erroneous results
      can be released to clients even though a batch meets the acceptance criteria. We
      tested a new approach that quantifies the cross-contamination of each sample and
      allows the scientist to make quality decisions with documentation. The approach
      will also detect carryover in over 90% of the wells. Briefly, two additional
      analytes were added as contamination markers. The markers were added to a multi
      well plate alternatively creating a pattern of a checkerboard. The spiked multi
      well plate was then used to perform the assay. If both markers were detected in a
      well, the sample was considered contaminated. The amount of the unexpected marker
      detected in a well measures the degree of contamination and may be used to make
      deactivation decisions. Depending on the relative impact of the contamination, a
      scientist can choose to tolerate the bias, reject the sample, reject the batch or
      raise the lower limit of quantitation for the batch. A guideline for rejection
      decisions is presented for discussion.

PMID- 16791865
TI  - High resolution 3T MRI for the assessment of cervical and superficial cranial
      arteries in giant cell arteritis.
AB  - A new high-resolution MR protocol for the combined assessment of neurovascular
      arterial anatomy and subsequent evaluation of inflammatory disease in cranial
      vessels walls has been investigated. First-pass contrast-enhanced MR angiography
      (CE-MRA) in combination with parallel imaging at high field permits the depiction
      of the neurovascular geometry with large coverage, including the aortic arch,
      supraaortic vessels, and almost the entire head, with high, submillimeter detail.
      Utilizing the remaining contrast agent, postcontrast T(1)-weighted turbo spin
      echo (TSE) imaging was used to generate late enhancement images of the vessel
      walls to assess the morphology and potential inflammatory changes in cranial
      arteries with high in-plane (195 x 260 microm(2)) spatial resolution. As a
      result, a combined analysis of neurovascular arterial anatomy as well as cranial
      vessel wall inflammations could be achieved in less than 45 minutes in all
      studies. The feasibility and clinical value for the diagnosis of rheumatologic
      diseases and simultaneous arteriosclerotic involvement was demonstrated in seven
      patients with suspected giant cell arteritis (GCA). Excellent CE-MRA image
      quality could be achieved and even vascular geometry of small superficial cranial
      arteries could be successfully visualized using single dose (0.1 mmol/kg)
      contrast agent administration and a dedicated phased-array head and neck coil at
      3T.

PMID- 16791867
TI  - In situ nucleophilic substitution reaction of N,N-dialkylaminoethyl-2-chlorides
      monitored by gas chromatography/mass spectrometry.
AB  - The detection and identification of degradation products of scheduled chemicals,
      which are characteristic markers of Chemical Warfare agents (CWAs), plays a key
      role in verification analysis. Identification of such non-scheduled but specific
      markers of CWAs helps in deciphering the kind of agent that was present in the
      sample submitted for off-site analysis. This paper describes the stability of N,N
      dialkylaminoethyl-2-chlorides, which are precursors for highly toxic chemicals
      like VX, in different solvents. These compounds are stable in chloroform,
      acetonitrile, hexane and dichloromethane but tend to undergo in situ nucleophilic
      substitution reaction in the presence of alcohols giving the corresponding alkyl
      ether. The study shows that N,N-dialkylaminoethyl alkyl ethers can be used as
      markers of N,N-dialkylaminoethyl-2-chlorides. A detailed degradation study of
      these compounds in the presence of alcohols was carried out and it was found that
      the reaction follows pseudo-first order kinetics. Electron ionization mass
      spectral data for the methyl ethers of all the compounds are briefly discussed.

PMID- 16791869
TI  - Formation of organometallic species from complexes of 2,5-diphenyl-1,3,4
      oxadiazole with some transition metal cations upon collision-induced
      dissociation.

PMID- 16791868
TI  - Measurement of paclitaxel and its metabolites in human plasma using liquid
      chromatography/ion trap mass spectrometry with a sonic spray ionization
      interface.
AB  - A quantitative liquid chromatography/ion trap mass spectrometry method for the
      simultaneous determination of paclitaxel, 6alpha-hydroxypaclitaxel and p-3'
      hydroxypaclitaxel in human plasma has been developed and validated. 6alpha-,p-3'
      Dihydroxypaclitaxel was also quantified using paclitaxel as a reference and
      docetaxel as an internal standard. The substances were extracted from 0.500 mL
      plasma using solid-phase extraction. The elution was performed with acetonitrile
      and the samples were reconstituted in the mobile phase. Isocratic high
      performance liquid chromatography analysis was performed by injecting 50 microL
      of reconstituted material onto a 100 x 3.00 mm C12 column with a methanol:1%
      trifluoroacetic acid/ammonium trifluoroacetate in H(2)O 70:30 mobile phase at 350
      microL/min. The [M+H](+) ions generated in the sonic spray ionization interface
      were isolated and fragmented using two serial mass spectrometric methods: one for
      paclitaxel (transition 854 --> 569 & 551) and the dihydroxymetabolite (transition
      886 --> 585 & 567) and one for the hydroxy metabolites (transition 870 --> 585 &
      567; transition 870 --> 569 & 551) and docetaxel ([M+Na](+), transition 830 -->
      550). Calibration curves were created ranging between 0.5 and 7500 ng/mL for
      paclitaxel, 0.5 and 750 ng/mL for 6alpha-hydroxypaclitaxel, and 0.5 and 400 ng/mL
      for p-3'-hydroxypaclitaxel. Adduct ion formation was noted and investigated
      during method development and controlled by mobile phase optimization. In
      conclusion, a sensitive method for simultaneous quantification of paclitaxel and
      its metabolites suitable for analysis in clinical studies was obtained.

PMID- 16791870
TI  - Defluorination degradation of trifluoromethyl groups identified by tandem mass
      spectrometry coupled with stable isotope incorporation strategy.

PMID- 16791871
TI  - Ultra-performance liquid chromatography/tandem mass spectrometric determination
      of testosterone and its metabolites in in vitro samples.
AB  - This paper describes the development and partial validation of a fast, sensitive
      and specific ultra-performance liquid chromatography/tandem mass spectrometric
      (UPLC/MS/MS) method for the determination of testosterone (T) and its four
      metabolites, 6beta-OH-T, 16alpha-OH-T, 16beta-OH-T and 2alpha-OH-T, in in vitro
      samples. The analytical method involves direct dilution of samples with
      acetonitrile containing an internal standard, followed by separation of
      testosterone and the four metabolites on an Acquity UPLCtrade mark C(18) column
      and detected by selected reaction monitoring (SRM) in positive ionization mode
      using turbo ionspray ionization. The parent compound and its metabolites
      investigated were well separated (Rs >1.5) with a run time of 4 min under a
      gradient condition. The method was partially validated. The linear concentration
      range was 0.01 to 5 microM for all the compounds of interest. Inter-assay mean
      bias and relative standard deviation (RSD) were in the range of -12% to 8% and
      4.1% to 8.5%, respectively. Intra-assay mean bias and RSD were in the range of 
      8.0% to 5.2% and 3.4% to 9.6%, respectively. The lower limit of quantitation for
      this assay was 0.01 microM. The differences in LC/MS performance were
      investigated by conducting a comparison of UPLC with another method previously
      optimized for HPLC-based separation and quantification of testosterone and its
      metabolites.

PMID- 16791872
TI  - A deflection system to reduce the interference from post-source decay product
      ions in photodissociation tandem time-of-flight mass spectrometry.
AB  - A deflection system consisting of four deflectors was designed and used to reduce
      the interference from post-source decay (PSD) product ions in photodissociation
      (PD) tandem time-of-flight (TOF) mass spectrometry. For simple protonated
      peptides generated by matrix-assisted laser desorption/ionization, the presence
      of PSD product ions at the laser irradiation spot was found to noticeably alter
      the minor peaks in the PD spectra even though the major ones were hardly
      affected. Other benefits from the use of the deflection system such as the
      improvement in the resolving power in PSD tandem mass spectra are discussed.

PMID- 16791874
TI  - Solid-state NMR spectra of paramagnetic silica-based materials: observation of
      29Si and 27Al nuclei in the first coordination spheres of manganese ions.
AB  - Some silica-based solids, prepared by the sol/gel method in the presence of high
      Mn2+ concentrations, have been characterized by the 29Si, 27Al MAS NMR spectra
      and 29Si T1 measurements. The single-pulse 29Si and 27Al MAS NMR spectra have
      shown broad spinning sideband patterns that are interpreted in terms of
      anisotropic bulky magnetic susceptibility (BMS) and dipole-field effects. In the
      absence of paramagnetic isotropic shifts, the 29Si and 27Al nuclei observed in
      the single-pulse NMR spectra have been assigned to nuclei remote from
      paramagnetic centers. It has been demonstrated that the 29Si and 27Al nuclei,
      which are in the vicinity of the manganese ions, can be detected by the Hahn-echo
      MAS NMR experiments at different carrier frequencies.

PMID- 16791873
TI  - Liquid chromatography/electrospray ionization tandem mass spectrometry analysis
      of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX).
AB  - A quantitative liquid chromatography/electrospray ionization tandem mass
      spectrometry (LC/ESI-MS/MS) method was developed for the analysis of the
      explosive, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). In negative
      ionization mode, HMX forms an acetate adduct ion [M + CH(3)COO](-), m/z 355, in
      the presence of a small amount of acetic acid in the mobile phase. The ESI
      collision-induced dissociation (CID) spectrum of m/z 355 was acquired and the
      transitions m/z 355 --> 147 and m/z 355 --> 174 were chosen for the determination
      of HMX in samples. Using this quantification technique, the method detection
      limit was 1.57 microg/L and good linearity was achieved in the range 5-500
      microg/L. This method will help to unambiguously analyze environmentally relevant
      concentrations of HMX.

PMID- 16791875
TI  - A comparison of chemical systems for luminometric determination of antioxidant
      capacity towards individual reactive oxygen species.
AB  - The aim of the study was to investigate the reactive oxygen species (ROS)
      production in the hypoxanthine-xanthinoxidase (HX-XO), hydrogen peroxide-ferrous
      sulphate (H2O2-FeSO4) and hydrogen peroxide (H2O2) systems by using various
      concentrations of ROS scavengers, such as superoxide dismutase (SOD),
      dimethylthiourea (DMTU) or catalase (CAT). Luminol (0.8 mmol/L) was dissolved in
      a borate buffer, pH 9.0, and was used as a luminophor in the chemiluminescence
      (CL) measurements. In the HX-XO system SOD, CAT and DMTU deepened the CL signal,
      whereas in the H2O2-FeSO4 system, only CAT and DMTU deepened the CL signal, and
      in the H2O2 system SOD and CAT increased and DMTU deepened the CL signal.
      Electron spin resonance (ESR) measurements were performed only in the H2O2-FeSO4
      system. 5,5-dimethyl-pyrroline-N-oxide (DMPO) was used as a spin trap. According
      to typical ESR spectra, .OH was produced in this chemical system. It can be
      concluded that the chemical systems do not produce single reactive oxygen species
      but a mixture of them.

PMID- 16791876
TI  - TCR ligand avidity determines the mode of B-Raf/Raf-1/ERK activation leading to
      the activation of human CD4+ T cell clone.
AB  - The interactions between peptide/MHC complexes and their cognate TCR are
      essential for various T cell responses. However, the relationship between the
      avidity of TCR ligand and the subsequent intracellular signaling through the TCR
      is still unclear. To investigate the effects of TCR ligand avidity on TCR
      mediated signaling, we established L cells expressing HLA-DR4 molecules
      covalently linked with agonistic peptide (high-affinity ligand) or altered
      peptide ligand (APL; low-affinity ligand) at various densities as APC for a
      cognate human CD4(+) T cell clone. Using this system, we demonstrated that the T
      cell clone stimulated with APL/HLA-DR4 complexes presented at an excessive
      density provoked the up-regulation of CD69, IL-2 production and proliferation,
      but no detectable phosphorylation of ZAP-70/LAT/SLP-76. Furthermore, in contrast
      to the high-affinity stimulation, the low-affinity stimulation evoked delayed and
      sustained activation of the B-Raf/extracellular signal-regulated kinase (ERK)
      pathway without Raf-1 activation. The strength and duration of B-Raf/ERK
      activations closely correlated with the density of the TCR ligand. A knockdown
      approach confirmed that B-Raf activation was indispensable for the APL-induced T
      cell responses. These observations suggest that the differences in TCR
      peptide/MHC interactions reflect the strength and duration of B-Raf/Raf-1/ERK
      activation in the human CD4(+) T cells.

PMID- 16791877
TI  - Immunoglobulin promotes the diversity and the function of T cells.
AB  - It is generally accepted in immunology that while T and B cells collaborate for
      the production of antibodies in response to protein antigens, T cells develop and
      function in the absence of B cells. However, B cell-deficient subjects and mice
      have unexplained cellular immune defects. Here, we examined the contribution of B
      cells/Ig to the generation of diversity and function of T cells. Mice lacking B
      cells and Ig (JH(-/-)) or having oligoclonal B cells (QM) had a profoundly
      contracted T cell receptor (TCR) Vbeta repertoire: 0.08 and 1.3% of wild type,
      respectively. Rejection of H-Y-incompatible skin grafts in QM and JH(-/-) mice
      was significantly delayed (median, 43 and 22 days, respectively) compared to wild
      type mice (median, 16 days). Furthermore, reduction of the TCR Vbeta diversity by
      thymectomy in wild-type mice significantly increased survival of H-Y-incompatible
      skin grafts, and reconstitution of the T cell diversity in QM mice with Ig Fab
      fragments significantly decreased survival of the skin grafts. These results
      indicate that B cells and/or Ig "help" T cells through the generation and
      maintenance of T cell diversity, improving T cell function. Our results may have
      important implications for therapy and immune reconstitution in the context of
      AIDS, cancer, autoimmunity and post-myeloablative treatments.

PMID- 16791878
TI  - Duration of CTL activation regulates IL-2 production required for autonomous
      clonal expansion.
AB  - The extent and magnitude of CD8(+) T lymphocyte (CTL) clonal expansion in vivo
      depends on the duration of stimulation provided during primary activation,
      whereas expansion under conventional in vitro conditions fails to reveal this.
      The molecular details of this differential programming are unclear. We developed
      a low-density culture system that recapitulates in vivo conditions and enables
      analysis of both proliferation and survival/apoptosis during primary expansion.
      We found that CTL given a prolonged stimulus produced more IL-2 and for a longer
      period than briefly activated CTL, and the IL-2 produced during the expansion
      phase was essential for cell proliferation and accumulation at low densities. CTL
      given a short stimulation and plated at low density followed the fate of briefly
      stimulated cells in vivo and underwent an abortive expansion and apoptosis,
      unless IL-2 was exogenously provided. Inhibition of apoptosis did not replace the
      requirement for IL-2 to drive clonal expansion. CTL primed for prolonged periods
      but in the absence of costimulation similarly behaved as though "partially
      programmed", undergoing abortive expansion at low densities. These results
      indicate that the nature and duration of antigenic stimulation regulate the
      autonomy of CTL expansion via the production of autocrine IL-2.

PMID- 16791879
TI  - Distinct roles for IL-6 and IL-12p40 in mediating protection against Leishmania
      donovani and the expansion of IL-10+ CD4+ T cells.
AB  - Adoptive dendritic cell (DC) immunotherapy provides a useful experimental tool to
      evaluate immunoregulation in vivo and has previously been successfully used to
      enhance host resistance in a variety of experimental models of leishmaniasis.
      Here, we used this approach to identify IL-6 and IL-12p40 as critical cytokines
      that cooperate to mediate host protection to Leishmania donovani but which act
      independently to regulate expansion of IL-10(+) CD4(+) T cells, shown here for
      the first time to be associated with this infection. Adoptive transfer of LPS
      activated bone marrow-derived DC (BMDC) from wild-type mice was therapeutically
      beneficial and led to enhanced resistance as measured by spleen parasite burden.
      In contrast, IL-6- or IL-12p40-deficient BMDC had no protective benefit,
      indicating that production of both cytokines was essential for the therapeutic
      efficacy of DC. IL-10 production by CD25(-) FoxP3(-) IL-10(+) CD4(+) T cells is a
      strong correlate of disease progression, and BMDC from wild-type mice inhibited
      expansion of these cells. Strikingly, IL-12-deficient BMDC could also inhibit the
      expansion of this T cell population whereas IL-6-deficient BMDC could not,
      indicating that IL-6 played a key role in this aspect of DC function in vivo.
      Breadth of cytokine production is thus an important factor when considering
      strategies for DC-based interventions.

PMID- 16791880
TI  - BAFF costimulation of Toll-like receptor-activated B-1 cells.
AB  - B cell-activating factor belonging to the TNF family (BAFF) and its receptor BAFF
      R play critical roles in the maturation and survival of conventional peripheral B
      cells. However, they appeared to be dispensable for the generation and
      maintenance of CD5(+) B-1 cells as BAFF(-/-) and BAFF-R(-/-) mice have normal B-1
      cell populations. Hence, it is presently unclear if B-1 cells are responsive to
      BAFF and if BAFF regulates some aspects of B-1 cell function. We show here that
      BAFF-R and transmembrane activator and CAML interactor (TACI) are the major
      receptors expressed by B-1 cells. Specifically, we show that BAFF treatment of B
      1 cells leads to increased NF-kappaB p100 processing and CD21/CD35 expression.
      Interestingly, toll-like receptor (TLR) engagement of B-1 cells augmented the
      surface expression of BAFF receptors and rendered them responsive to BAFF
      costimulation, as evidenced by their increased proliferation, expression of cell
      surface activation markers and secretion of the pro-inflammatory cytokine IL-6
      and the anti-inflammatory cytokine IL-10. This costimulatory effect is achieved
      primarily through BAFF-R as BAFF failed to costimulate B-1 cells obtained from
      A/WySnJ mice which have defective BAFF-R signaling. Thus, as TLR are innate
      immune receptors and B-1 cells are "innate-like" lymphocytes, our data provide
      evidence that BAFF plays a role in innate immunity.

PMID- 16791881
TI  - Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung
      cells.
AB  - Lyn is an important B cell signaling kinase of the Src tyrosine kinase family
      with a broad range of functions from cytoskeletal changes to induction of
      apoptosis. However, the role of Lyn in infectious diseases is not clear. Here, we
      demonstrate that Lyn activation by phosphorylation significantly impacted
      invasion of an alveolar epithelial cell line, primary lung cells, and rat lungs
      by Pseudomonas aeruginosa (PA), a common opportunistic lung pathogen affecting
      individuals with deficient lung immunity. Our results indicate that activation of
      Lyn and its interaction with rafts and TLR2, played an important role in the
      initial stages of PA interaction with host cells. The role of Lyn was further
      evaluated using the pharmacologic Src-specific inhibitor PP2, a dominant negative
      mutant, and finally confirmed with Lyn-deficient (Lyn(-/-)) bone marrow-derived
      mast cells. Inhibition of Lyn's function by above approaches prevented PA
      internalization. Moreover, blocking of Lyn also affected downstream events:
      induction of inflammatory cytokines and apoptosis. This report brings out a new
      role of Lyn in infectious diseases and indicates potential new targets for
      prevention and treatment of infections.

PMID- 16791882
TI  - Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells
      and is independent of CD57 expression.
AB  - The generation of high-affinity antibody-secreting plasma cells critically
      depends on the presence of CD4 T cells during the germinal center (GC) reaction.
      GC T cells are so far incompletely characterized in terms of phenotype and
      function. Here, we show that human follicular B helper T (T(FH)) cells are
      characterized by high expression of the homeostatic chemokine receptor CXCR5 and
      the costimulatory molecule ICOS, but not CD57 expression. CXCR5(hi)ICOS(hi) CD4 T
      cells are the most potent inducers of IgG production that also secrete large
      amounts of the B cell-attracting chemokine CXCL13. CXCR5(hi)ICOS(hi) CD4 T cells
      differ from other tonsillar CD4 T cell subsets in their stimulatory activity,
      proliferative capacity and susceptibility to apoptosis. Large-scale gene
      expression analysis revealed that T(FH) cells are only distantly related to
      CXCR5(-) and CXCR5(+) central memory T (T(CM)) as well as effector memory T
      (T(EM)) cells present in the periphery. CXCR5(hi)ICOS(hi) CD4 T cells appear to
      be terminally differentiated T helper cells that express a unique set of
      transcription factors related to the Notch signaling pathway and thus
      differentiate independent of other T helper cell populations.

PMID- 16791883
TI  - How T lymphocytes switch between life and death.
AB  - While insufficient cell death of activated T cells can result in autoimmune
      disorders, elimination of too many T cells can lead to immunodeficiency.
      Therefore, T lymphocyte fate is highly regulated and requires that cells can
      switch from an apoptosis-resistant towards an apoptosis-sensitive state. This
      switch is tightly controlled by various effector molecules. Basically, two
      separate pathways control the fate of antigen-activated T cells: activation
      induced cell death (AICD) and activated T cell autonomous death (ACAD).
      Autoreactive T lymphocytes are eliminated by restimulation via their T cell
      receptor (TCR) and undergo AICD involving death receptors (extrinsic pathway). In
      contrast, ACAD can lead to T cell deletion without TCR restimulation, and is
      determined by the ratio between anti- and pro-apoptotic Bcl-2 family members at
      the mitochondria (intrinsic pathway). While the extrinsic and the intrinsic
      pathway lead to caspase activation, non-caspase proteases (e.g., cathepsins) can
      be released by the lysosomes and might contribute to AICD as well as to ACAD.
      Activated T cells poses cell death escape mechanisms which are needed for
      survival of (memory) T cells, but are deleterious for autoimmune disorders or
      progression of T cell lymphomas.

PMID- 16791884
TI  - Coy decoy with a new ploy: interceptor controls the levels of homeostatic
      chemokines.
AB  - A new subfamily of chemokine receptors is emerging that do not signal along
      classical G-protein-mediated pathways. Instead, these "silent" receptors
      efficiently internalize their cognate chemokine ligands, hence their suggested
      name, "chemokine interceptors", for internalizing receptors. Two of these
      interceptors, DARC and D6, possess intriguing patterns of tissue expression and
      are believed to be involved in controlling the local levels of proinflammatory
      chemokines. In this issue of the European Journal of Immunology, the biochemical
      properties of a third silent chemokine receptor, CCX-CKR, have been characterized
      and it is suggested that it may act as a scavenger for homeostatic chemokines,
      pointing to a broad and significant role for this group of chemokine binding
      molecules in chemokine biology.

PMID- 16791885
TI  - Powerful carbon-carbon bond forming reactions based on a novel radical exchange
      process.
AB  - Xanthates and related derivatives have proved to be extremely useful for both
      inter- and intramolecular radical additions. The broad applicability of the
      intermolecular addition to un-activated olefins opens tremendous opportunities
      for synthesis, since various functional groups can be brought together under mild
      conditions and complex structures can be rapidly assembled. The presence of the
      xanthate in the product is also a powerful asset for further modifications, by
      both radical and non-radical pathways. Of special importance is the access to
      highly substituted aromatic and heteroaromatic derivatives and the synthesis of
      block polymers through a controlled radical polymerisation mediated by various
      thiocarbonylthio group containing agents (RAFT and MADIX processes).

PMID- 16791886
TI  - Guanine oxidation: one- and two-electron reactions.
AB  - Guanine bases in DNA are the most sensitive to oxidation. A lot of effort has
      been devoted to the understanding of the chemical modifications of guanine under
      different oxidizing conditions, the final goal being to know which lesions in DNA
      can be expected in vivo and their biological consequences. This article analyses
      the mechanisms underlying guanine oxidation by the comparison between one- and
      two-electron transfer processes. The different oxidants used in vitro give
      complementary answers. This overview presents a choice of some key intermediates
      and the predictive description of G-oxidation products that can be generated from
      these intermediates depending on the reaction conditions.

PMID- 16791887
TI  - Laser-induced release of encapsulated materials inside living cells.

PMID- 16791888
TI  - A nonanuclear dysprosium(III)-copper(II) complex exhibiting single-molecule
      magnet behavior with very slow zero-field relaxation.

PMID- 16791889
TI  - Self-assembly of a highly stable, topologically interesting metallamacrocycle by
      bridging gold (I) ions with pyridyl-2,6-diphenyl 2- and diphosphanes.

PMID- 16791890
TI  - First evidence for a uniquely spin-polarized quartet photoexcited state of a pi
      conjugated spin system generated via the ion-pair state.

PMID- 16791891
TI  - Porous coordination polymer with pi Lewis acidic pore surfaces,
      {[Cu3(CN)3{hat(CN)3(OEt)3}].3 THF}n.

PMID- 16791892
TI  - Hollow and tin-filled nanotubes of single-crystalline in OH3 grown by a solution
      liquid-solid-solid route.

PMID- 16791893
TI  - Synthesis, optical properties, and self-assembly of ultrathin hexagonal In2S3
      nanoplates.

PMID- 16791894
TI  - Cyclodextrin-based side-chain polyrotaxane with unidirectional inclusion in
      aqueous media.

PMID- 16791895
TI  - Tris(organozinc) phosphazenates as templates for trimeric and hexameric zinc
      oxide clusters.

PMID- 16791896
TI  - Immunosuppressive role of semaphorin-3A on T cell proliferation is mediated by
      inhibition of actin cytoskeleton reorganization.
AB  - Timely negative regulation of the immune system is critical to allow it to
      perform its duty while maintaining it under tight control to avoid
      overactivation. We previously reported that the neuronal receptor neuropilin-1
      (NP-1) is expressed in human lymph nodes. However, the role of NP-1 interaction
      with its physiological ligand semaphorin-3A (Sema-3A) on immune cells remains
      elusive. Here we show that Sema-3A is expressed by activated DC and T cells, and
      that its secretion in DC/T cell cocultures is delayed. Sema-3A/NP-1 interaction
      down-modulated T cell activation since addition of Sema-3A in DC/T cell
      cocultures dramatically inhibited allogeneic T cell proliferation. More
      importantly, neutralization by blocking antibodies or by antagonist peptide of
      endogenous Sema-3A produced by DC/T cell cocultures resulted in a 130% increase
      in T cell proliferation. Sema-3A acted directly on T cells, since it could block
      anti-CD3/CD28-stimulated proliferation of T cells. Finally, immunomodulatory
      functions of Sema-3A relied on the blockage of actin cytoskeleton reorganization,
      affecting TCR polarization and interfering with early TCR signal transduction
      events such as ZAP-70 or focal adhesion kinase phosphorylation. Therefore, we
      propose that Sema-3A secretion and the resulting NP-1/Sema-3A interaction are
      involved in a late negative feedback loop controlling DC-induced T cell
      proliferation.

PMID- 16791897
TI  - The chemokine receptor CCX-CKR mediates effective scavenging of CCL19 in vitro.
AB  - The chemokines CCL19, CCL21 and CCL25, by signalling through the receptors CCR7
      or CCR9, play critical roles in leukocyte homing. They also bind another
      heptahelical surface protein, CCX-CKR. CCX-CKR cannot couple to typical chemokine
      receptor signalling pathways or mediate chemotaxis, and its function remains
      unclear. We have proposed that it controls chemokine bioavailability. Here, using
      transfected HEK293 cells, we have shown that both CCX-CKR and CCR7 mediate rapid
      CCL19 internalisation upon initial chemokine exposure. However, internalised
      CCL19 was more efficiently retained and degraded after uptake via CCX-CKR. More
      importantly, CCR7 rapidly became refractory for CCL19 uptake, but the
      sequestration activity of CCX-CKR was enhanced. These properties endowed CCX-CKR
      with an impressive ability to mediate progressive sequestration and degradation
      of large quantities of CCL19, and conversely, prevented CCR7-expressing cells
      from extensively altering their chemokine environment. These differences may be
      linked to the routes of endocytosis used by these receptors. CCX-CKR, unlike
      CCR7, was not critically dependent on beta-arrestins or clathrin-coated pits.
      However, over-expression of caveolin-1, which stabilises caveolae, blocked CCL19
      uptake by CCX-CKR while having no impact on other chemokine receptors, including
      CCR7. These data predict that CCX-CKR scavenges extracellular chemokines in vivo
      to modify responses through CCR7.

PMID- 16791898
TI  - Higher-order CpG-DNA stimulation reveals distinct activation requirements for
      marginal zone and follicular B cells in lupus mice.
AB  - Mouse follicular B cells express TLR9 and respond vigorously to stimulation with
      single-stranded CpG-oligodeoxynucleotides (ODN). Surprisingly, follicular B cells
      do not respond to direct stimulation with other TLR9 ligands, such as bacterial
      DNA or class A(D) CpG-ODN capable of forming higher-order structures, unless
      other cell types are present. Here, we show that priming with interferons or with
      B cell-activating factor, or simultaneous co-engagement of the B cell receptor
      for antigen (BCR), can overcome this unresponsiveness. The effect of interferons
      occurs at the transcriptional level and is mediated through an
      autocrine/paracrine loop, which is dependent on IRF-1, IL-6 and IL-12 p40. We
      hypothesize that the lack of bystander activation of follicular B cells with more
      complex CpG ligands may be an important safety mechanism for avoiding
      autoimmunity. This will prevent resting B cells from responding to foreign or
      self-derived hypomethylated double-stranded CpG ligands unless these ligands are
      either delivered through the B cell receptor or under conditions where B cells
      are simultaneously co-engaged by activated plasmacytoid dendritic cells or TH1
      cells. A corollary is that the heightened responsiveness of lupus B cells to TLR9
      induced stimulation cannot be ascribed to unprimed follicular B cells, but is
      rather mediated by hypersensitive marginal zone B cells.

PMID- 16791899
TI  - Reversible photochemical conversion of helicity in self-assembled nanofibers from
      a 1,omega-thymidylic acid appended bolaamphiphile.

PMID- 16791900
TI  - Formation of acetic acid by aqueous-phase oxidation of ethanol with air in the
      presence of a heterogeneous gold catalyst.

PMID- 16791901
TI  - Exceptionally strong electronic communication through hydrogen bonds in porphyrin
      C60 pairs.

PMID- 16791902
TI  - Polyhedral silver nanocrystals with distinct scattering signatures.

PMID- 16791903
TI  - Copper(I) alkynyl clusters, [Cu(x+y)(hfac)(x)(C[triple chemical bond]CR)(y)],
      with Cu(10)-Cu(12) cores.
AB  - The facile syntheses and the structures of five new Cu(I) alkynyl clusters,
      [Cu(12)(hfac)(8)(C[triple chemical bond]CnPr)(4)(thf)(6)]xTHF (1),
      [Cu(12)(hfac)(8)(C[triple chemical bond]CtBu)(4)] (2), [Cu(12)(hfac)(8)(C[triple
      chemical bond]CSiMe(3))(4)] (3), [Cu(10)(hfac)(6)(C[triple chemical
      bond]CtBu)(4)(diethyl ether)]/[Cu(10)(hfac)(6)(C[triple chemical
      bond]CtBu)(3)(C[triple chemical bond]CnPr)(diethyl ether)] (4) and
      [Cu(10)(hfac)(6)(C[triple chemical bond]CtBu)(4)(diethyl ether)] (5) are
      reported, in which hfacH=1,1,1,5,5,5-hexafluoropentan-2,4-dione. The first
      independent molecule found in the crystals of 4 (4 a) proved to be chemically
      identical to 5. The Cu(10) and Cu(12) cores in these clusters are based on a
      central "square" Cu(4)C(4) unit. Whilst the connectivities of the Cu(10) or
      Cu(12) units remain identical the geometries vary considerably and depend on the
      bulk of the alkynyl group, weak coordination of ether molecules to copper atoms
      in the core and CuO intramolecular contacts formed between Cu-hfac units on the
      periphery of the cluster. Similar intermolecular contacts and interlocking of Cu
      hfac units are formed in the simple model complex [Cu(2)(hfac)(2)(HC[triple
      chemical bond]CtBu)] (6). When linear alkynes, C(n)H(2n+1)C[triple chemical
      bond]CH, are used in the synthesis and non-coordinating solvents are used in the
      workup, further association of the Cu(4)C(4) cores occurs and clusters with more
      than eighteen copper atoms are isolated.

PMID- 16791904
TI  - Electronic origin for enhanced nonlinear optical response of complexes from
      tetraalkylammonium halide and carbon tetrabromide: electrostatic potentials of
      intermolecular donor-acceptor dyads.
AB  - Electronic origin for nonresonant enhancement of nonlinear optical response in
      the complexes formed from tetraalkylammonium halide and carbon tetrabromide is
      provided in view of electrostatic potentials of intermolecular donor (halide ion)
      acceptor (CBr(4)). The calculated electrostatic potentials of donor-acceptor
      range from -4.83 to -7.70 kcal mol(-1) and show a decreasing order of [Et(4)Cl(
      )Br] > [Et(4)Br(-)Br] congruent with [Et(4)I(-)Br] > [Bu(4)Br(-)Br]. The
      calculated second-order susceptibilities of solid complexes are in an increasing
      order of [NEt(4)ClCBr(4)] < [NEt(4)BrCBr(4)] congruent with [NEt(4)ICBr(4)] <
      [NBu(4)BrCBr(4)C(3)H(6)O]. It has been shown that the donor/acceptor dyads make
      the exclusive contribution to nonlinear optical response. A large size of halide
      or tetraalkylammonium ion results in a small electrostatic potential and large
      nonlinear optical response in these charge-transfer complexes. It indicates that
      a small supermolecular interaction will create a large nonlinear optical
      response, and it gives a clue to design the molecular complexes with large non
      linear optical susceptibility.

PMID- 16791905
TI  - A combined superiority and non-inferiority approach to multiple endpoints in
      clinical trials.
AB  - Treatment comparisons in clinical trials often involve multiple endpoints. By
      making use of bootstrap tests, we develop a new non-parametric approach to
      multiple-endpoint testing that can be used to demonstrate non-inferiority of a
      new treatment for all endpoints and superiority for some endpoint when it is
      compared to an active control. It is shown that this approach does not incur a
      large multiplicity cost in sample size to achieve reasonable power and that it
      can incorporate complex dependencies in the multivariate distributions of all
      outcome variables for the two treatments via bootstrap resampling.

PMID- 16791906
TI  - psbA mutation (Asn266 to Thr) in Senecio vulgaris L. confers resistance to
      several PS II-inhibiting herbicides.
AB  - DNA sequence analysis of the psbA gene encoding the D1 protein of photosystem II
      (PS II), the target site of PS II-inhibiting herbicides, identified a point
      mutation (Asn266 to Thr) in a bromoxynil-resistant Senecio vulgaris L. population
      collected from peppermint fields in Oregon. Although this mutation has been
      previously reported in Synechocystis, this is the first report of this particular
      point mutation in a higher plant exhibiting resistance to PS II-inhibiting
      herbicides. The resistant population displayed high-level resistance to
      bromoxynil and terbacil (R/S ratio 10.1 and 9.3, respectively) and low-level
      resistance to metribuzin and hexazinone (R/S ratio 4.2 and 2.6, respectively)
      when compared with the susceptible population. However, the population was not
      resistant to the triazine herbicides atrazine and simazine or to the urea
      herbicide diuron. A chlorophyll fluorescence assay confirmed the resistance
      levels and patterns of cross-resistance of the whole-plant studies. The resistant
      S. vulgaris plants produced fewer seeds. Differences in cross-resistance patterns
      to PS II-inhibiting herbicides and the difference in fitness cost could be
      exploited in a weed management program.

PMID- 16791908
TI  - A 3D structural and conformational study of procyanidin dimers in water and hydro
      alcoholic media as viewed by NMR and molecular modeling.
AB  - The three-dimensional structures of 5 procyanidin dimers have been determined in
      a hydro-alcoholic medium and in water using 2D NMR and molecular mechanics. They
      are made from monomers of catechin (CAT) and epicatechin (EPI)-B1: EPI-CAT, B2:
      EPI-EPI, B3: CAT-CAT, B4: CAT-EPI and B2g: EPI-EPI-3-O-gallate. These tannins
      exist in two conformations that are in slow exchange in the NMR timescale (s),
      one is compact and the other extended. The compact form is found to dominate (76
      98%) when the dimer is made of at least one CAT monomer (B1, B3, B4). Both forms
      are found in even proportions only in the case of procyanidin B2. The latter
      tannin can be converted into a dominant compact form when the lower EPI unit is
      galloylated. The finding of a predominant compact form for procyanidin dimers is
      discussed in relation with tannin-saliva protein interactions that are of
      importance for the wine-tasting/making processes.

PMID- 16791907
TI  - Antifeedant and toxicity effects of thiophenes from four Echinops species against
      the Formosan subterranean termite, Coptotermes formosanus.
AB  - Over 220 crude extracts from repositories generated from plants native to Greece
      and Kazakhstan were evaluated for termiticidal activity against the Formosan
      subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae).
      Emerging from this screening effort were bioactive extracts from two Greek
      species (Echinops ritro L. and Echinops spinosissimus Turra subsp. spinosissimus)
      and extracts from two Kazakhstan species (Echinops albicaulis Kar. & Kir. and
      Echinops transiliensis Golosh.). Fractionation and isolation of constituents from
      the most active extracts from each of the four species has been completed,
      resulting in the isolation of eight thiophenes possessing varying degrees of
      termiticidal activity. 2,2':5',2"-Terthiophene and 5'-(3-buten-1-ynyl)-2,2'
      bithiophene demonstrated 100% mortality against C. formosanus within 9 days at 1
      and 2 wt% concentrations respectively. In addition, all but two of the eight
      compounds tested were significantly different from the solvent controls in the
      filter paper consumption bioassay.

PMID- 16791910
TI  - 1H, 13C and 15N NMR spectral characterization of twenty-seven 1,2-diaryl-(4E)
      arylidene-2-imidazolin-5-ones.
AB  - 1H, 13C and 15N NMR chemical shifts and couplings (n)J(H,C) in DMSO-d(6) at 30
      degrees C have been determined for 1,2-diaryl-(4E)-arylidene-2-imidazolin-5-one
      derivatives 1-27. Their chemical shift assignments are based on PFG DQF 1H,1H
      COSY, PFG 1H,13C HMQC as well as PFG 1H,13C and 1H,15N HMBC experiments. For
      compounds 1-10 including aryl fluorine substituent(s) also the couplings
      (n)J(F,C) (n = 1 - 4) are reported.

PMID- 16791911
TI  - Resistance of avocado thrips (Thysanoptera: Thripidae) to sabadilla, a
      botanically derived bait.
AB  - Bioassays were conducted on four avocado thrips (Scirtothrips perseae Nakahara)
      populations in southern California that had had limited past exposure to the
      botanical pesticide sabadilla, with the objective of establishing baseline
      susceptibility levels for the purpose of resistance monitoring. Reports of
      avocado thrips resistance in a grove that had received six sabadilla sprays over
      2 years were confirmed when a bioassay indicated resistance ratios of 7.6 and
      18.8 at the LC50 and LC90, respectively. Owing to the availability of other
      unrelated pesticides, sabadilla sprays were discontinued at this site, and, after
      5.5 years, resistance ratios had dropped to near baseline levels. Avocado thrips
      baseline susceptibility to cyfluthrin was also obtained from one grove for future
      resistance monitoring studies. Resistance management principles are discussed in
      relation to the limited future options available for avocado thrips control.

PMID- 16791912
TI  - Estimation of benchmark dose for renal dysfunction in a cadmium non-polluted area
      in Japan.
AB  - Previously, the association between urinary cadmium (Cd) concentration and
      indicators of renal dysfunction, including beta(2)-microglobulin (beta(2)-MG),
      total protein and N-acetyl-beta-D-glucosaminidase (NAG) were investigated in 1270
      inhabitants > or = 50 years of age (547 men, 723 women) in a Cd non-polluted area
      in Japan and showed that a dose-response relationship existed between renal
      effects and Cd exposure in the general environment without any known Cd
      pollution. However, the threshold levels of urinary Cd could not be estimated at
      that time. In the present study, the threshold levels of urinary Cd were
      estimated as the benchmark dose low (BMDL) using the benchmark dose (BMD)
      approach. Urinary Cd excretion was divided into 6-7 categories, and an
      abnormality rate was calculated for each. Cut-off values for urinary substances
      were defined as corresponding to the 84% upper limit values, which were
      calculated from 2034 persons who had been living in the non-polluted areas and
      did not smoke. Then the BMD and BMDL were calculated using a log-logistic model.
      The values of BMD and BMDL for all urinary substances could be calculated. The
      BMDL for the 84% cut-off value of beta(2)-MG, setting an abnormal value at 5%,
      was 2.0 microg g(-1) creatinine (cr) in men and 1.6 microg g(-1) cr in women. In
      conclusion, the present study demonstrated that the threshold level of urinary Cd
      could be estimated in people living in the general environment without any known
      Cd-pollution in Japan, and the value was inferred to be almost the same as that
      in Belgium and Sweden.

PMID- 16791913
TI  - Effects on the central and peripheral nervous activity in rats elicited by acute
      administration of lead, mercury and manganese, and their combinations.
AB  - Adult male Wistar rats were treated with inorganic lead, mercury and manganese,
      and their double combinations, in acute application. The aim was to study the
      effects on spontaneous and stimulus-evoked cortical, and evoked peripheral,
      nervous activity, to detect any interaction of the metals and any correlation
      between the changes caused in the spontaneous and stimulus-evoked electrical
      activity of the primary somatosensory cortical area, and the compound action
      potential of the tail nerve. In the frequency distribution of the spontaneous
      cortical activity, a shift to lower frequencies was seen. The cortical responses
      evoked by whisker or tail stimulation showed an increase of the peak-to-peak
      amplitude and peak latency on administration of the metals and metal
      combinations. With the metal combinations, synergism was observed. Correlations
      found between alterations of the spontaneous and evoked, or between cortical and
      peripheral, activity were evaluated in terms of mechanism. According to the
      results, combined exposure to the three heavy metals studied might lead to
      synergistic action, indicating an increased health risk in settings with exposure
      to several heavy metals.

PMID- 16791914
TI  - New York groups battle over HIV testing consent policies.

PMID- 16791915
TI  - Funding. Federal AIDS bill provides more funding for Southern states.

PMID- 16791916
TI  - Preliminary injunction granted over global prostitution flap.

PMID- 16791917
TI  - Disclosure. Teacher prevails in student's emotional distress claim.

PMID- 16791918
TI  - Exposure. Ailments caused by HIV prophylactic constitute injury.

PMID- 16791919
TI  - HIV testing upheld for sex offender.

PMID- 16791920
TI  - HIV and methamphetamines. States battle HIV exposure via new meth laws, funding.

PMID- 16791922
TI  - Global. Clinton Foundation supports antidiscrimination policies.

PMID- 16791921
TI  - Exposure. Inmate's sentence doubled for exposing officer to HIV.

PMID- 16791923
TI  - Order for HIV testing affirmed for incestuous sex offender.

PMID- 16791924
TI  - Prison. Inmate's claim of ineffective HIV care is time-barred.

PMID- 16791925
TI  - Discrimination. HIV segregation still lawful in Georgia prisons.

PMID- 16791926
TI  - Successful transfusion of Kp (a-b+) red cells incompatible for auto anti-Kpb.

PMID- 16791927
TI  - Myeloablative conditioning in myelofibrosis using i.v. treosulfan and autologous
      peripheral blood progenitor cell transplantation with high doses of CD34+ cells
      results in hematologic responses. A follow-up of three patients.

PMID- 16791928
TI  - Update on emerging infections from the Centers for Disease Control and
      Prevention. Severe Clostridium difficile-associated disease in populations
      previously at low risk--four states, 2005.

PMID- 16791929
TI  - Evidence-based emergency medicine. What is the preferred first-line therapy for
      status epilepticus?

PMID- 16791930
TI  - Evidence-based emergency medicine. Clinical assessment of acute cholecystitis in
      adults.

PMID- 16791931
TI  - Primary pancreatic lymphoma. A report of five cases.

PMID- 16791932
TI  - Pioneers in cardiology. An interview with Philipp Bonhoeffer by Robert Short.

PMID- 16791933
TI  - Viewpoint: cardiac rehabilitation. Interview with Guy De Backer by Jennifer
      Taylor.

PMID- 16791934
TI  - [Relevance of the choice of proton pump inhibitors].

PMID- 16791935
TI  - Energy issues challenge mindsets...

PMID- 16791936
TI  - . . . but climate change indicators grow apace.

PMID- 16791937
TI  - Igor Dawid.

PMID- 16791938
TI  - Creating a buzz.

PMID- 16791940
TI  - Mechanical fix for fluid overload. During a heart failure crisis, filtering the
      blood works as well as drugs to remove excess fluid.

PMID- 16791939
TI  - Plavix isn't for everyone. Adding Plavix to aspirin doesn't help people without
      heart disease.

PMID- 16791941
TI  - Better heart attack prediction from new cholesterol test? Two simple tests could
      someday elbow aside, or at least complement, today's standard cholesterol tests.

PMID- 16791942
TI  - A new wave in heart testing. An odd variation on the electrocardiogram could help
      doctors determine who would get the most benefit from an implanted defibrillator.

PMID- 16791943
TI  - Heave-ho for homocysteine? High doses of B vitamins lower homocysteine but don't
      fix heart disease.

PMID- 16791944
TI  - Pacemakers and mammograms.

PMID- 16791945
TI  - Little support for that sinking feeling.

PMID- 16791947
TI  - New hurricane season sparks discussions about lessons learned. STD/HIV officials
      say communications were a major problem.

PMID- 16791948
TI  - No easy task: finding clients post-hurricane. Many still have not returned to
      Louisiana.

PMID- 16791946
TI  - Ask the doctor. For the last few years, I have been experiencing what I think are
      mini-strokes. The first time it happened, I lost the sight in one eye for about a
      minutes. Sometimes the vision in both eyes gets blurred for a few minutes. A few
      weeks ago I could not think of the word "battery" while talking with a friend.
      Otherwise, I am a healthy 77-year-old who exercises, isn't overweight, and
      doesn't smoke. My doctor hasn't suggested any tests of courses of action. Can
      you?

PMID- 16791949
TI  - Program links newly HIV-diagnosed patients to care. Intervention uses well
      trained case finders.

PMID- 16791950
TI  - CDC to remove pre-test counseling requirements. Latest stats: nearly half of
      infected are black.

PMID- 16791951
TI  - Opt-out system for HIV testing proves successful. More are tested and referred to
      care.

PMID- 16791952
TI  - FDA issues guidance about HIV vaccine study.

PMID- 16791953
TI  - AIDS: the first 25 years.

PMID- 16791954
TI  - Guideline watch. HIV treatment guidelines updated.

PMID- 16791955
TI  - Antiretroviral rounds. CD4 count 423, viral load 12,000: time to treat anyway?

PMID- 16791956
TI  - 13th Conference on Retrovirus and Opportunistic Infections. Update on
      experimental HIV drugs. The newest, latest pipeline drugs from CROI.

PMID- 16791957
TI  - 13th Conference on Retrovirus and Opportunistic Infections. What's new, pussycat?
      HIV and the battle for the vagina.

PMID- 16791958
TI  - 13th Conference on Retrovirus and Opportunistic Infections. Metabolics and HIV.
      Update from the 13th CROI.

PMID- 16791959
TI  - 13th Conference on Retrovirus and Opportunistic Infections. Don't rush to HIV
      treatment. Looking at the nuances of that possibly alarming report.

PMID- 16791960
TI  - One one one: U.S. Representative Jan Schakowsky, (D-IL). The politics of HIV.
      Interview by Jeff Berry.

PMID- 16791961
TI  - Hepatitis B: the other hepatitis virus. Treatment for HBV.

PMID- 16791962
TI  - HIV treatment series. Treatment interruptions. Reviewing what we've learned so
      far.

PMID- 16791963
TI  - AIDS @ 25. Personal reflections on the epidemic.

PMID- 16791964
TI  - The dawn of a new treatment. A look at experimental HIV integrase inhibitors.

PMID- 16791965
TI  - Preliminary studies on the inhibition of D-sorbitol-6-phosphate 2-dehydrogenase
      from Escherichia coli with substrate analogues.
AB  - D-Sorbitol-6-phosphate 2-dehydrogenase catalyzes the NADH-dependent conversion of
      D-fructose 6-phosphate to D-sorbitol 6-phosphate and improved production and
      purification of the enzyme from Escherichia coli is reported. Preliminary
      inhibition studies of the enzyme revealed 5-phospho-D-arabinonohydroxamic acid
      and 5-phospho-D-arabinonate as new substrate analogue inhibitors of the F6P
      catalyzed reduction with IC50 values of (40 +/- 1) microM and (48 +/- 3) microM
      and corresponding Km/IC50 ratio values of 14 and 12, respectively. Furthermore,
      we report here the phosphomannose isomerase substrate D-mannose 6-phosphate as
      the best inhibitor of E. coli D-sorbitol-6-phosphate 2-dehydrogenase yet reported
      with an IC50 = 7.5 +/- 0.4 microM and corresponding Km/IC50 ratio = about 76.

PMID- 16791966
TI  - [Risky eating behaviors in student population in Mexico City: trends 1997-2003].
AB  - OBJECTIVE: The main purpose of this study was to identify the trends of risky
      eating behaviors among student population in Mexico City in the period 1997-2003
      and its relationship with sex age and family head educational level. METHODS:
      Data from the 1997 (N = 9,755), 2000 (N = 3,286) and 2003 (N = 3,062) Drug and
      Alcohol Prevalence in Student Population of Mexico City Survey's were analyzed.
      These are representative data of students of junior high, high school and
      technical schools in Mexico City, with a mean age of 14.5 years (SD = 1.9).
      Eating behaviors were assessed with a brief questionnaire developed following DSM
      IV diagnostic criteria. Risky eating behaviors and the number of risk indicators
      were compared by sex, age and family head educational level. RESULTS: The results
      showed an overall increase in the percentage of males (from 1.3% in 1997 to 3.8%
      in 2003), and females (3.4% in 1997 to 9.6% in 2003) who showed 3 or more risky
      eating behaviors. The analysis by age groups showed an increase in all but 16-17
      year old males, and in all females, being 12-13 year old males and 18-19 year old
      females the most affected. Regarding the type of risk indicators in both sexes
      and across all age groups, an increase in preoccupation towards gaining weight
      and the use of purging and restrictive methods to loose weight was observed. Body
      weight overestimation decreased in males, while in females showed an increase
      along with binges in the 2000 survey but showed a decrease after that (2003
      survey). The relationship between the family head educational level and risky
      eating behaviors did not show a regular pattern among males, while a positive
      relationship between both variables was found among females. CONCLUSIONS: A first
      overall view of the situation of risky eating behaviors among adolescent students
      in Mexico City and the changes observed in the period studied. An increase of
      these behaviors was observed along the period of study, being younger males and
      older females the most affected, as well as women whose family head showed higher
      educational level.

PMID- 16791967
TI  - The CONSORT Statement: revised recommendations for improving the quality of
      reports of parallel-group randomized trials 2001.
AB  - To comprehend the result of a randomized controlled trial (RCT), readers must
      understand its design, conduct, analysis and interpretation. That goal can be
      achieved only through complete transparency from authors. Despite several decades
      of educational efforts, the reporting of RCTs needs improvement. Investigators
      and editors developed the original CONSORT (Consolidated Standards of Reporting
      Trials) statement to help authors improve reporting by using a checklist and flow
      diagram. The revised CONSORT statement presented in this article incorporates new
      evidence and addresses some criticism of the original statement. The checklist
      items pertain to the content of the Title, Abstract, Introduction, Methods,
      Results, and Comment. The revised checklist includes 22 items selected because
      empirical evidence indicates that not reporting the information is associated
      with biased estimates of treatment effect or because the information is essential
      to judge the reliability or relevance of the findings. We intended the flow
      diagram to depict the passage or participants through an RCT. The revised flow
      diagram depicts information from 4 stages of a trial (enrollment, intervention
      allocation, follow-up and analysis). The diagram explicitly includes the number
      of participants, according to each intervention group, included in the primary
      data analysis. Inclusion of these numbers allows the reader to judge whether the
      authors have performed an intention-to-treat analysis. In sum, the CONSORT
      statement is intended to improve the reporting or an RCT, enabling readers to
      understand a trial's conduct and to assess the validity of its results.

PMID- 16791968
TI  - Selected proceedings of the Sixth Asian Congress for Microcirculation. February
      24-26, 2005. Tokyo, Japan.

PMID- 16791969
TI  - Aquatic processes and systems in perspective.

PMID- 16791970
TI  - Like our very own: adoption and the changing culture of motherhood, 1851-1950.
      [Review of: Berebitsky, J.  Like our very own: adoption and the changing culture
      of motherhood, 1851-1950.  Lawrence: U. Pr. of Kansas, 2000].

PMID- 16791971
TI  - Serious adverse events and the modafinil augmentation study.

PMID- 16791972
TI  - [Image of the month. Meckel's diverticulitis caused by parasitosis, specifically,
      Ascaris lumbricoides].

PMID- 16791973
TI  - The sanitary city: urban infrastructure in America from colonial times to the
      present. [Review of: Melosi, M.V. The sanitary city: urban infrastructure in
      America from colonial times to the present. Baltimore: Johns Hopkins U. Pr.,
      2000].

PMID- 16791974
TI  - The meanings of blindness in nineteenth-century America.

PMID- 16791975
TI  - Health care home run: Massachusetts' new universal health care law has everyone
      watching.

PMID- 16791976
TI  - Digital doctors: telemedicine improves medical care in remote areas, but faces
      some policy obstacles.

PMID- 16791977
TI  - An improved assay for adenylyl cyclase.

PMID- 16791979
TI  - Linear ion trap/Orbitrap mass spectrometer.

PMID- 16791978
TI  - Nanoparticle aerosol mass spectrometer.

PMID- 16791980
TI  - Long-term effects of Exxon Valdez. Are there lingering problems from one of the
      world's worst oil spills?

PMID- 16791981
TI  - Chiral recognition mechanisms.

PMID- 16791982
TI  - Monolithic materials: Promises, challenges, achievements.

PMID- 16791983
TI  - CE: Moving away from specialists.

PMID- 16791984
TI  - Teaching sex: the shaping of adolescence in the 20th century.  [Review of: Moran,
      J.P.  Teaching sex: the shaping of adolescence in the 20th century.  Cambridge,
      Mass.: Harvard U. Pr., 2000].

PMID- 16791985
TI  - Medicalized motherhood: perspectives from the lives of African-American and
      Jewish women.  [Review of: Litt, J.S.  Medicalized motherhood: perspectives from
      the lives of African-American and Jewish women.  New Brunswick, N.J.: Rutgers U.
      Pr., 2000].

PMID- 16791986
TI  - Questions feline parasite survey methods.

PMID- 16791987
TI  - Invasive Haemophilus influenzae disease in Manitoba in the post-vaccination era
      suggests a changing epidemiology.

PMID- 16791988
TI  - Appreciates efforts to expand veterinary technician programs.

PMID- 16791989
TI  - There are no facts, only interpretations.

PMID- 16791990
TI  - Kinetic proteomics of melanoma tumors.

PMID- 16791991
TI  - How the muscle proteome changes as time goes by.

PMID- 16791992
TI  - HUPO Plasma Proteome Project: challenges and future directions.

PMID- 16791993
TI  - Repatriation reader: who owns American Indian remains?  [Review of: Mihesuah,
      D.A., ed.  Repatriation reader: who owns American Indian remains?  Lincoln: U. of
      Nebraska Pr., 2000].

PMID- 16791994
TI  - The price of a gift: a Lakota healer's story.  [Review of: Mohatt, G. and Eagle
      Elk, J.  The price of a gift: a Lakota healer's story.  Lincoln: U. of Nebraska
      Pr., 2000].

PMID- 16791995
TI  - Micro-computed tomography evaluation of the glenoid fossa and mandibular condyle
      bone after bilateral vertical ramus mandibular distraction in a canine model.
AB  - The aim of this study was to quantify bone microarchitecture within the glenoid
      fossa and mandibular condyle following mandibular distraction osteogenesis. Eight
      6- to 9-month-old male beagle dogs underwent bilateral vertical mandibular
      distraction with semiburied distractors (12 days of distraction at 1 mm per day).
      One unoperated animal served as control. After distraction the animals were
      divided into two groups (N = 4) and killed after 1 or 2 months of consolidation.
      Three-dimensional trabecular architecture was analyzed by micro-computed
      tomography (microCT). At both sites the overall trends were similar. In the
      glenoid fossa, there was decreased bone volume, trabecular number, and
      connectivity density and increased trabecular separation at 1 month and decreased
      trabecular thickness and increased structure model index compared with the
      control (P < 0.05). In the mandibular condyle, there was decreased bone volume,
      trabecular number, and connectivity density at both 1 and 2 months, with
      decreased trabecular thickness and increased structure model index at 2 months
      only compared with the control (P < 0.05). The bone became less dense and more
      rodlike. These bone changes are similar to those seen by the effects of aging or
      impaired normal function. Thus, in the short term, changes occur in the bone
      microstructure of the glenoid fossa and mandibular condyle after vertical
      mandibular ramus distraction in the canine model.

PMID- 16791996
TI  - Losing ground: physician income, 1995-2003.
AB  - Between 1995 and 2003, average physician net income from the practice of medicine
      declined about 7 percent after adjusting for inflation, according to a national
      study from the Center for Studying Health System Change (HSC). The decline in
      physicians' real income stands in sharp contrast to the wage trends for other
      professionals who saw about a 7 percent increase after adjusting for inflation
      during the same period. Among different types of physicians, primary care
      physicians fared the worst with a 10.2 percent decline in real income between
      1995 and 2003, while surgeons' real income declined by 8.2 percent. But medical
      specialists' real income essentially remained unchanged. Physicians reported
      working slightly fewer hours overall but spent more time on direct patient care.
      Flat or declining fees from both public and private payers appear to be a major
      factor underlying declining real incomes for physicians. The downward trend in
      real incomes since the mid-1990s likely is an important reason for growing
      physician unwillingness to undertake pro bono work, including charity care and
      volunteering to serve on hospital committees.

PMID- 16791997
TI  - Welcome to the first issue of Women and Birth: The journal of the Australian
      College of Midwives.

PMID- 16791998
TI  - Midwifery: "at the edge of history".
AB  - The paper focuses on possible future pathways in maternity care for midwives and
      nations to consider. The paper blends personal and professional experiences to
      outline priority areas facing midwives in the future. It begins by examining
      maternal mortality and morbidity in the developing world and considering the
      potential of the ten high priority action messages (1997) in helping to improve
      the plight of women and children in the future. The paper then examines major
      issues facing midwives in the developed world including: the way birth is viewed;
      the medical-midwifery divide; marketing midwifery; and finally the challenge of
      dealing with fear around birth. The third part of the paper examines a part of
      society where the two worlds meet and there are issues from both the developed
      and developing world to consider. The paper focuses on women from culturally and
      linguistically diverse communities, Aboriginal and Torres Strait Islander women
      and women birthing in remote and rural areas. By looking at these three worlds
      separately the paper examines different concerns facing midwives in the future
      but also draws on common issues that face us all as citizens of this planet and
      particularly as predominantly women. The paper challenges midwives to be
      politically active and dare to change the world.

PMID- 16791999
TI  - Health professional's knowledge and awareness of perinatal depression: results of
      a national survey.
AB  - INTRODUCTION: Postnatal depression affects 14% of women, occurring also
      antenatally, with potential long-term consequences, making it an important
      disorder to detect and manage early. In this study we sought to examine knowledge
      and awareness of perinatal depression in health professionals involved in
      perinatal care throughout Australia prior to the implementation of a
      comprehensive screening program, aimed at improving detection and access to
      appropriate management. METHODS: A random sample of General Practitioners (GPs)
      and Maternal Child Health Nurses (MCHNs) and Midwives, in regions throughout
      Australia to be subsequently targeted by a screening and education program, were
      invited to participate. Responses to a hypothetical vignette and a knowledge
      questionnaire, as well as details of experience were completed. FINDINGS:
      Questionnaires were completed by 246 GPs, 338 MCHNs and 569 midwives, with
      overall response rates; GP's 23%; MCHN's 55% and midwives 57%. Although knowledge
      level was similar among professional groups, MCHNs had higher levels of awareness
      of perinatal depression. Both GPs and MCHNs were more likely than midwives to
      recognize the need for providing help to women with emotional distress.
      Depression was more likely to be considered postnatally than antenatally in all
      groups, with GPs most likely to provide this diagnosis. GPs had a significant
      propensity to recommend antidepressants, and midwives to select non-specific
      medications. CONCLUSIONS: Health professionals responding to this survey had a
      high awareness and similar knowledge base. Further education on antenatal
      depression and the safety risks and alternatives to medication is important for
      all groups, but particularly important for midwives and GPs. The latter is
      especially relevant given the preference for women with perinatal depression not
      to use pharmacological interventions to treat their emotional distress.

PMID- 16792001
TI  - A midwife program of newborn resuscitation.
AB  - A very small proportion of newborns fail to establish a normal respiratory
      pattern without some assistance at birth and newborns requiring resuscitative
      measures at birth should have a skilled practitioner able to provide it. In this
      small hospital midwives felt unskilled in newborn resuscitation and
      paediatricians were not always immediately available. A stakeholder group
      gathered to discuss the problem. A training program was implemented that improved
      the skills, confidence and support of the attending midwife to resuscitate the
      newborn effectively. The aim was to improve the outcome for the infant whilst
      maintaining the mother's choice of birthing in a small local hospital close to
      family and friends.

PMID- 16792000
TI  - Women's experience of revealing perinatal bladder function--implications for
      midwifery care.
AB  - Comments of women engaged in a longitudinal study of urinary leaking from first
      trimester to 12 months following birth provide the data for this paper. Useful
      insights into the factors contributing to the maintenance of silence and ways to
      break the barriers to discussion of urinary incontinence before, during and
      following pregnancy were revealed. Given the prevalence of 30% of Australian
      women experiencing urinary leaking following pregnancy, it is imperative that
      midwives engage in discussion and support prevention of this unwelcome outcome of
      childbirth.

PMID- 16792002
TI  - Postoperative management of elective esophagectomy for cancer.
AB  - Postoperative management after elective esophagectomy for cancer has not been
      standardized. Thoracoabdominal incision with associated pain, extended operative
      time with consequent extracellular fluid shifts, single lung ventilation,
      potential for prolonged postoperative mechanical ventilation and comorbidities in
      patients with esophageal cancer, all contribute to high perioperative risk.
      Respiratory problems remain the major cause of both mortality and morbidity after
      esophagectomy for cancer. A specific pulmonary disorder, acute respiratory
      distress syndrome (ARDS) occurs in 10-20% of patients after esophagectomy. ARDS
      mortality exceeds 50%. Atrial fibrillation, that complicates recovery in 20 to
      25% of patients after esophagectomy, contributes to make outcome worse.
      Anesthesiologists should adopt strategies known to be able to optimize patient
      outcome. Decreased postoperative mortality and morbidity have been associated
      with epidural analgesia, bronchoscopy to clear persistent bronchial secretions,
      intraoperative fluid restriction and early extubation. It has been shown that
      setting up early respiratory physiotherapy and mobilitation may improve
      functional recovery.

PMID- 16792003
TI  - Rehabilitation in esophageal cancer.
AB  - Cancer of the esophagus has an unfavorable prognosis with a five-year survival
      rate after radical surgery of less than 10%; early diagnosis is difficult. The
      appearance of symptoms, particulary dysphagia, is due to more than 2/3 tumor
      involvement of the esophageal circumference, already present in 2/3 of patients
      at diagnosis. Symptoms can be local and/or systemic; they can be physical,
      psychic, iatrogenic and evolutive. A careful rehabilitation program should follow
      these patients during the entire course of their disease The rehabilitation
      approach intends to define areas of intervention, short-term goals, possible
      achievements, role of health operators and overall verifications. Common problems
      of patients with esophageal cancer, are analyzed. A rehabilitation program
      including the patient care throughout the hospitalization period to improve
      his/her autonomy with respect to his/her social and familial activities, is
      illustrated.

PMID- 16792004
TI  - Postoperative care after esophagectomy: the surgeon's view.
AB  - Although in the past esophagectomy was associated with high rates of morbidity
      and mortality, currently specialized centers have reported reduced hospital death
      rates of less than 10%. This reduction has been mainly attributed to preoperative
      patient selection, improvements in anesthesia, surgical techniques, and
      postoperative care management. In recent years, clinical care pathways, namely
      physician-directed clinical plans, have been developed to standardize
      postoperative care after specific surgical procedures: primary goals are
      improvement in quality of care and reduction in hospital costs. These pathways
      could be planned after identification of the complications with the highest
      incidence and the highest hospital costs in order to optimally allocate
      resources. Aim of this study is to delineate an ideal clinical care pathway after
      esophagectomy by reporting the most common complications with an overview of
      advances in perioperative care and providing pointers to what might be
      achievable.

PMID- 16792005
TI  - Esophageal cancer staging: the role of radiology.
AB  - In esophageal cancer staging, the radiologic approach is represented by tumor
      identification, preoperative staging, and re-staging after neoadjuvant therapies.
      At present, while barium radiography shows a high sensitivity for early and
      advanced tumors, endoscopy is always necessary for confirmation. CT and MRI are
      the gold standard for preoperative staging of advanced (T4) esophageal cancer and
      for evaluation of distant metastasis; however they still show a low sensitivity
      in the study of possible regional lymph node involvement, in differentiating
      residual disease and scarring; in particular the esophageal wall cannot be
      carefully examined.

PMID- 16792006
TI  - Laparoscopic gastroplasty for esophagectomy.
AB  - Minimally invasive surgery is currently becoming an accepted approach to
      esophageal cancer treatment. At the authors' Department laparoscopic gastroplasty
      is used in combination to either transhiatal or transthoracic esophagectomy,
      associated with left cervicotomy and right thoracotomy, respectively. Outcomes of
      laparoscopic and open gastric mobilization during esophagectomy in terms of intra
      and postoperative complications are compared. From February 2003 to September
      2005 45 patients underwent laparoscopic gastroplasty (group A) and 26 patients
      underwent open gastroplasty (group B) during esophagectomy. Intraoperative
      complications were 2% vs. 11.5%; respiratory complications were 2.2% vs. 19%;
      leakages from the suture lines were 17.7% vs. 7.6% (p = n.s.); major long-term
      complications were 4.4% vs 3.8% (p = n.s.), respectively. Laparoscopic
      gastroplasty during esophagectomy was shown to be a safe procedure.
      Intraoperative splenic lesions were rare; respiratory complications seemed
      decreased after the laparoscopic approach in comparison to open gastroplasty;
      major long-term complications were specific to the open or laparoscopic approach.

PMID- 16792007
TI  - Adjuvant radiotherapy and radiochemotherapy in the management of esophageal
      cancer: a review of the literature.
AB  - Surgical resection remains the mainstay treatment for esophageal cancer and the
      failure of surgery alone is attributed to the systemic nature of the disease at
      the time of presentation. In an effort to improve local control of the disease
      that should correspond to a benefit in survival, postoperative adjuvant schemes
      of treatment have been explored. Current standard treatment, and future
      implications in light of the new knowledge are analyzed, based on the present
      literature. The possibility of different treatments in relation to different
      histology findings, is stressed.

PMID- 16792008
TI  - The role of lymphadenectomy in esophageal cancer.
AB  - The role of lymph node dissection for resectable esophageal carcinoma has
      remained controversial, addressed by two contradictory groups of surgeons: the
      more conservative ones considering esophageal carcinoma with lymph node
      metastasis to be a systematic disease and the others, supporters of extended
      lymph node dissection, viewing the metastatic disease phenomenon in sequential
      manner. In favor of extended lymphadenectomy that allows better postoperative
      staging, there are also the consistent event of skipping metastasis and the high
      rate of micrometastasis found mostly with immunohistochemical testing. The
      discussed concept of sentinel lymph node evaluation does not seem a feasible
      approach to esophageal cancer. Although there are not undoubted results that
      three-field resection may offer a survival benefit, before these techniques can
      be widely adopted, we need more experience and randomized studies to substantiate
      the benefit of such radical surgery.

PMID- 16792009
TI  - Role of induction therapy in esophageal cancer.
AB  - Esophageal cancer ranks sixth among the causes of death from cancer worldwide.
      Patients undergoing surgery have a median survival ranging from 13 to 19 months;
      2-year survival rates range from 35 to 42 percent, and 5-year survival rates from
      15 to 24 percent. In particular, the 3 year survival (= SVV) is about 26%, with a
      median survival of 17 months. An interesting point is that about 20-25% of the
      patients has only locoregional involvement as pattern of failure. At least two
      randomized studies reported about the combined use of radiotherapy and
      chemotherapy as sensibilization. They assessed that patients treated with
      chemoradiation had a longer median survival compared to patients receiving
      radiation therapy alone, both in early and advanced stages. Moreover
      radiochemotherapy seems able of achieving high rates of downstaging and of
      increasing overall and disease-free survival.

PMID- 16792010
TI  - Preoperative assessment and risk factors in the surgical treatment of esophageal
      cancer: the role of age.
AB  - Esophageal cancer is essentially a disease of the elderly. Several studies
      suggested that age per se should not be considered a risk factor for surgical
      mortality and morbidity, and access to surgical treatment should not be denied
      only on the basis of age. Indeed, advanced age may represent an indicator of
      several factors such as comorbidity or poor physical performance which in turn
      can increase surgical risk and dramatically reduce life expectancy. Therefore, a
      careful preoperative assessment of these factors, with particular regard to
      comorbid conditions (such as cardiovascular and pulmonary diseases), the
      physiological status, and social habits is necessary in elderly adults. In
      consideration of the need of a multidisciplinary assessment to identify
      comorbidities and operative risk, a close collaboration of pneumologists,
      cardiologists, radiologists, oncologists, thoracic surgeons, anesthesiologists,
      geriatric specialists, physical therapists is highly recommendable.

PMID- 16792012
TI  - Medicolegal aspects of esophageal cancer surgery.
AB  - Forensic implications of esophageal cancer surgery are varied and complex
      depending on the field of specialization involved i.e. civil law, criminal law,
      insurance or social security and for the distinct probative requirements related
      to each field. The aim of this article is to reconstruct the logical procedure of
      a forensic doctor who actually examines a practical case to establish the
      profiles of professional responsibility in particular in civil or criminal law.

PMID- 16792011
TI  - Preoperative anesthetic evaluation and preparation in patients requiring
      esophageal surgery for cancer.
AB  - Esophagectomy for carcinoma of the esophagus is associated with significant
      mortality and morbidity. Patients with esophageal cancer have frequently
      obstruction with dysphagia and they often develop malnutrition. In addition,
      patients can suffer from chronic aspiration leading to a poor preoperative
      respiratory status. Thorough preoperative evaluation is essential for assessing
      the operative risk in the individual patient. Respiratory and cardiac problems
      are the most common complications and assessment of surgical risk, preoperative
      performance status, particularly with regard to pulmonary and cardiac risk, is
      likely to be the most important factor. Clinical findings are more predictive of
      pulmonary complications than results of testing. Cardiac risk is evaluated
      according to the American College of Cardiology (ACC)/American Heart Association
      guidelines. With the identification of risk factors, patients undergoing
      esophageal surgery could be stratified. Appropriate preoperative risk-reduction
      strategies can be used to decrease morbidity and mortality rates associated with
      esophagectomy for cancer.

PMID- 16792013
TI  - The surgeon's approach to preoperative evaluation of esophageal cancer: recent
      developments.
AB  - Esophageal resection for cancer is still associated with high morbidity and
      mortality. Postoperative complications may be either patient- or surgeon-related.
      Patient-related factors include age, malnutrition, immunodepression and
      associated diseases. Surgeon-related factors are surgical experience, hospital
      volume and multidisciplinary approach. In the last 20 years major improvements
      and new technologies have been proposed and applied in esophageal surgery: its
      evolution depended on a thorough knowledge of surgical anatomy and technique, as
      well as on important developments in pre- and postoperative care. Preoperative
      evaluation is defined as the process of clinical assessment that precedes the
      induction of anesthesia. The principle is to gain information about the patient
      that could lead to modify his/her management, and improve outcome.

PMID- 16792014
TI  - Staging of esophageal carcinoma: endoscopic ultrasonography.
AB  - Endoscopic ultrasonography (EUS) has gained ground in the staging of esophageal
      cancer because of its high accuracy in determining depth of tumor invasion
      (greater than 80%) and lymph node metastases. The accuracy of EUS increases with
      increasing stage. However within T1 tumors, EUS performance in distinguishing
      mucosal (T1m) form submucosal invasion (T1sm) is poor. In this context high
      frequency ultrasonography probes can play a major role. The advent of EUS-guided
      fine-needle aspiration (EUS-FNA) has dramatically changed the impact of EUS on
      nodal staging, providing cytological confirmation of malignancy from peritumoral
      and celiac lymph nodes. Especially celiac node metastases, have a major clinical
      impact on patient management. Widespread use of EUS in the staging of esophageal
      cancer should be encouraged. However, EUS should not be considered as first line
      test for evaluation of these patients and should always be performed after
      negative CT or PET/CT.

PMID- 16792015
TI  - [Effect of lox-sites of the Cre lox recombination system on promoterless bar gene
      expression in transgenic plants].
AB  - We demonstrate that localization of lox site between the right border of T-DNA
      and promoterless bar gene (RB-lox-bar-) led to its highly efficient expression in
      transgenic plants of Nicotiana tabacum and N. africana. Plasmid vectors used in
      gene integration experiments contained neomycin phosphotransferase II (npt II)
      gene under nos promoter as well. Transgenic plants were selected according to
      their capacity to grow on the medium with kanamycin and then they were tested on
      the selective medium containing phosphinothricin. 80% of transgenic plants
      expressed bar gene at the level similar to that in plants transformed with the
      bar gene under widely used constitutive promoter. Transformation of plants with
      the plasmid vector containing only promoterless bar gene near T-DNA right border
      (RB-bar-) and with the vector containing lox site and promoterless bar gene in
      the middle of the construction (-lox-bar-) led to obtaining no more than 4.5% of
      transgenic plants resistant to phosphinothricin. PCR analyses confirmed both the
      absence of tandem repeats and of plasmid recombination resulting in transference
      of bar gene under promoter in plasmid vector. Nos-terminator situated between the
      lox site and the right border of T-DNA did not decrease bar gene expression.

PMID- 16792016
TI  - [Construction of three-dimensional models of Arabidopsis thaliana FtsZ-proteins
      on basis of crystal structure of archaebacterial FtsZ-GDP complex].
AB  - Three-dimensional models of FtsZ-protein complexes with GDP from Arabidopsis
      thaliana L. localized in cytosol (Entrez database code NP190843) and in
      chloroplasts (Entrez database code AAA82068) were developed. Crystal structure of
      the FtsZ-GDP complex from archaea Methanococcus jannaschii (PDB-code 1FSZ) was
      used as a matrix. Secondary structures of computed models contain ten beta
      strands. A chloroplast form of FtsZ-protein has ten alpha-helices and four 3(10)
      helices, whereas cytosolic form of protein has nine and three structures
      correspondently and neither a0-helix before nucleotide-binding domain nor C
      terminal 3(10)-helix in secondary domain. The T2-loop of nucleotide-binding
      pocket of chloroplast form of FtsZ-ptotein in position 111 contains non-charged
      alanin residue instead of the charged one which is typical for cytosolic and
      bacterial forms of proteins. At low sequence homology of FtsZ-proteins
      (approximately 47%) the developed models demonstrate high coincidence with matrix
      both in the structures of nucleotide-binding pocket and in the whole molecule.
      The models are completely suitable for further studies of possible sites of
      binding with dinitroaniline herbicides.

PMID- 16792017
TI  - [Inheritance of glume length and grain length in hybridisation of Triticum
      polonicum with hard wheat].
AB  - Inheritance of glume length and grain length in the hybrids Triticum polonicum
      with T. durum cv. Kharkivs'ka 19 has been studied. The results show that the
      "polonicumity" complex inherits as unfully recessive and monogene trait. Positive
      correlation between glume length and grain length has been shown. It has been
      revealed that more exact plant distribution to segregation classes is observed
      for the glume at the second floret than at the first one.

PMID- 16792018
TI  - [Duration of the period before heading and test for allelism in Ppd-lines of
      different origin].
AB  - The duration of periods to heading has been compared in lines which carry various
      Ppd genes from different institutions. Test for allelism has been conducted
      between these lines. Ppd-B1a gene is allelic to Ppd3 gene of near isogenic line
      Mironovskaya 808 (the set of SGI). In the set of SGI lines Ppd1 gene is allelic
      to Ppd-A1a. These two genes are non-allelic to the known Ppd-D1a gene.

PMID- 16792019
TI  - [Cytogenetical peculiarities of tetraploid sugar beet pollinators].
AB  - Cytogenetical monitoring and analysis of plant morphological features of
      artificially created sugar beet tetraploid population (C5) were conducted. Four
      types of tetraploids differing in pollen quality were selected. It was shown that
      seeds of triploid hybrids received from diploid plants cross-fertilised by
      tetraploids were notable for increased germinating capacity.

PMID- 16792020
TI  - [Alterations of nucleolar DNA localization caused by simulated microgravity].
AB  - The functions of the nucleolus responsible for the biosynthesis of ribosomes in
      altered gravity are still unclear. The location of nucleolar DNA both in control
      and simulated microgravity has been investigated using fluorescent and immunogold
      cytochemistry. We have determined the redistribution of rDNA in the nucleolar
      components accompanied by their ultrastructure changes. According to this the
      lowering of rDNA transcription level under simulated microgravity was supposed.

PMID- 16792021
TI  - [Population-genetic study of the polymorphism of structural genes and ISSR-PCR
      markers in some cattle breeds].
AB  - The comparative analysis of genetic structures of five cattle breeds has been
      carried out using polymorphism of two different types of molecular-genetic
      markers--20 structural genes and 128 DNA loci (the DNA fragments flanked by
      inverted microsatellite loci repetitions--ISSR-PCR method). In spite of
      availability of breed-specific singularities of genotype distribution detected by
      the both methods the level of mean heterozygosity of structural genes was similar
      in all the investigated breeds. A part of polymorphic loci and the average value
      of the polymorphic information contents (PIC) of ISSR-PCR markers has appeared
      much higher in commercial breeds with high effective number in comparison with
      Ukrainian autochthonous breeds. The population-genetic processes detected by
      different methods are discussed.

PMID- 16792022
TI  - [Ultrastructural organization of carcinoma Lewis (3LL) cells during cisplatin
      resistance formation].
AB  - The electron-microscopic analysis of the morphological status of 3LL (Lewis)
      carcinoma tumour cells in the process of cisplatin resistant phenotype formation
      has been performed. It was shown that selection of tumour cells forming cell
      clones characterized by more complicated nuclear and cytoplasm organization took
      place. The tumour cells had the diffused nuclear chromatin; nuclear envelope had
      the numerous pores with expanded diaphragms. The prominent nucleoli consisted of
      the active centres surrounded by considerable areas of the condensed nucleolar
      chromatin. Cell cytoplasm contained the well-developed Goldgi complex and the
      numerous well-structured myelinoid formations in the form of dense-wrapped
      concentric membrane structures. The obtained data can morphologically confirm the
      hypothesis of Gately D.P. and Howel S.B., 1993, thain the process of resistant
      phenotype formation the tumour cells can create the cellular mechanisms to remove
      the drug from the cell and to correct the damages of the cellular nucleus and
      cytoplasm.

PMID- 16792023
TI  - [Cytomorphological characteristics of dendritic cells].
AB  - Five morphological degrees of maturity of dendritic cells induced from monocytes
      of peripheral blood in oncological patients have been revealed using originally
      prepared and stained cytological preparations. Cytological examination of
      dendritic cells can be used for their identification in production of dendritic
      cell antitumor vaccines.

PMID- 16792024
TI  - [Amino-modified probes with immobilized linkers and proteins for atomic force
      microscopy].
AB  - Functionalized by bovine serum albumin (BSA) probes for atomic force microscopy
      (AFM) which can be used for molecular recognition studies has been obtained.
      Modification and functionalization procedure of AFM probe includes three stages.
      First, amino probes were obtained by modification in vapors of amino silane
      derivative. Then surface amino groups of the amino probe interacted with
      homobifunctional amino reactive crosslinker. And finally, the probe with
      covalently attached crosslinker was functionalized by BSA molecules. Obtained AFM
      probes were characterized on the different stages of the modification by force
      measurements and the adhesion forces were determined. Process of modification was
      confirmed by visualization of BSA and supercoiled pGEMEX DNA molecules
      immobilized on the standard amino mica and amino mica modified by crosslinker.

PMID- 16792025
TI  - [Flecainide acetate utilisation review among general practitioners and hospital
      or office-based cardiologists in France. Obepine: observational study of
      flecainide].
AB  - A pharmacoepidemiological cross-sectional observational study was performed among
      a representative sample of French general practitioners and cardiologists. The
      aim of this study was to describe the prescription modalities of flecainide
      acetate, an Ic class antiarrhythmic, and how these modalities match the marketing
      authorization and the current summary of product characteristics. A total of 941
      physicians participated in the study, 496 GPs and 445 cardiologists, and 1116
      patients treated with flecainide for more than one month were included. On
      average, the patients were 68.7-years-old and 54% of them were women. Most of the
      initial flecainide prescriptions came from cardiologists (96%) and the check-up
      included an electrocardiogram (98%), a Holter monitoring (56%) and/or an
      echocardiography (71%). The preferred indication was supraventricular rhythm
      disorders (95%) and mostly atrial fibrillation (63%). A small proportion of
      coronary patients (7%) and of patient suffering from cardiac insufficiency (4%)
      was found. Flecainide was prescribed with a median posology of 150 mg per day,
      mostly as LP form (64%). Overall, the indications specified in the summary of
      product characteristics were respected in 90% of the cases, the contraindications
      in 91% of the cases and the patient follow-up was appropriate in 99% of the
      cases. In conclusion, the study showed that the prescription's conditions of
      flecainide in France complied with the summary of product characteristics data
      for most of the prescribing physicians with a respect of the indications,
      contraindications and management recommendations in 84% of the cases.

PMID- 16792026
TI  - [Respective interest of two techniques of electrophysiological study in patient
      without heart disease].
AB  - Electrophysiologic study (EPS) frequently is required to assess the prognosis of
      asymptomatic Wolff-Parkinson-White syndrome (WPW) or to prove the nature of no
      documented tachycardia. EPS usually is performed by intracardiac route and
      hospitalization is required. Similar data are given by an EPS performed by
      oesophageal route during a consultation. The purpose of the study was to evaluate
      the cost of both techniques in France. Transesophageal EPS was performed during a
      consultation in 100 patients with asymptomatic WPW syndrome and 100 patients with
      no heart disease, complaining of no documented tachycardias with abrupt beginning
      and end, suggesting a paroxysmal junctional re-entrant tachycardia (PJRT). The
      cost of transesophageal study including isoproterenol infusion is 127.75 euros.
      The cost of intracardiac EPS is at least 1460 euros, cost of hospitalization
      during only one day. RESULTS: In patients with WPW syndrome, 15 had a potentially
      malignant form with the induction of a tachycardia conducted through the
      accessory pathway at a high rate (> 240/min in control state, > 300/min with
      isoproterenol); radiofrequency catheter ablation was indicated in a second time.
      In the group with no documented tachycardia, PJRT was induced in 30 patients and
      indication of ablation was discussed. In other 155 patients with either a benign
      form of WPW syndrome or with a tachycardia unrelated to a PJRT, hospitalization
      was not required; in these patients, intracardiac study performed during one day
      of hospitalization would have costed 226,300 Euros. The cost for the esophageal
      EPS and a similar diagnosis was 19,801 Euros, with a save money of 206,499 Euros.
      In 45 patients in whom hospitalization was indicated in a second time to perform
      catheter ablation of the arrhythmia, the cost related to esophageal EPS was 5749
      Euros. In the total group, considering the final diagnosis and the need of
      hospitalization in 45 patients, the save money related to the use of esophageal
      EPS was 206,499 E-5749 E = 200,750 euros. CONCLUSIONS: We should take into
      account the cost studies, when various techniques could be used for a similar
      diagnosis. There are important differences in the cost of diagnostic methods and
      it is easy to decrease this cost.

PMID- 16792027
TI  - [Risk stratification in atrial and ventricular arrhythmias].
AB  - Atrial fibrillation, the most frequent arrhythmia, has a growing incidence with
      increasing age and the most important complication of the disease is
      thromboembolic events that may be prevented by antivitamin K. They are the most
      efficient therapeutic class for the prevention of these events but they are
      associated with an increased haemorrhagic risk leading to a reduced prescription
      in general practice. Optimisation of the management should be based on an
      individual evaluation of the thromboembolic and haemorrhagic risks, taking into
      account age, the presence of an associated heart disease, hypertension, diabetes,
      history of cerebrovascular event, history of previous haemorrhagic event and the
      ability to achieve a stable target INR. The challenge in ventricular arrhythmias
      lies in identifying a high risk of sudden death, mainly related to ventricular
      fibrillation. In patients with structural heart disease, left ventricular
      dysfunction is the strongest predictor of sudden death. Non invasive markers such
      as non sustained ventricular tachycardia, late ventricular potentials, decreased
      heart rate variability and baroreflex sensitivity, and repolarization altemans
      are further elements to assess risk. However, most of these markers have a poor
      positive predictive value and a low specificity. In patients with normal hearts,
      genetic predisposition may in the future identify high risk patients. The
      electrophysiologic study with programmed ventricular stimulation remains a costly
      and invasive method and only has a strong positive predictive value in ischemic
      cardiomyopathy. More precise algorithms for risk stratification are thus needed
      that may help the strategy of therapy with prophylactic implantable cardioverter
      defibrillator in the future.

PMID- 16792028
TI  - [Sensitization of tilt-table testing for syncope of unknown etiology: which drug
      to use?].
AB  - OBJECTIVE: The sensitivity of tilt-table testing in the diagnosis of vasovagal
      syncope is between 30% and 50% only. The most common method currently used to
      improve the sensitivity of the test is the administration of isoproterenol i.v.
      However, this method is difficult to perform and time consuming. The objective of
      our study was to compare sublingual trinitrin administration to i.v.
      isoproterenol during tilt-table testing. METHODS: We analyzed the results of 257
      consecutive patients referred for tilt testing. Patients who had a negative test
      received either a ten minutes infusion of i.v. isoproterenol at the dose of 4
      mcg/kg/min, or 0.4 mg of trinitrin given sublingually. RESULTS: Two hundred (and)
      fifty-seven patients underwent tilt-table testing. In the first group
      (isoproterenol group), 42 patients (39%) had a spontaneous positive tilt test,
      compared to 45 patients (31%) in the trinitrin group (P = NS). After
      sensitization, 24 additional patients (22%) had a positive test in the
      isoproterenol group vs 55 patients (37%) in the trinitrin group (P = NS). The
      total number of positive tests was 66 (61%) in the isoproterenol group compared
      to 100 (68%) in the trinitrin group (P = NS). CONCLUSION: Sublingual trinitrin is
      at least as good as IV isoproterenol during tilt-table testing. Because trinitrin
      is simpler to use and because its administration is much faster than
      isoproterenol, it should be recommended as the drug of choice to improve the
      sensitivity of tilt-table testing.

PMID- 16792029
TI  - [Conductive disorders following open-heart valvular surgery. Concerning 230
      operated patients].
AB  - AIMS: Conductive disorders following open-heart valvular surgery represent
      serious complications that may require definitive pacemaker implantation. The
      natural history of these troubles is not well established thus, controversy
      persist concerning the timing of pacemaker implantation. In this study we
      identify the predictive factors of permanent conductive disorders in order to
      assess the optimal time of pacing. METHODS AND RESULTS: Two hundred thirty
      valvular replacements were done between 1993 and 2003. The mean age of our
      patients was 42 +/- 13.4 years. Rheumatic valvulopathies accounted for 76% of
      cases, with 54% of multiple valvulopathies. Twenty-two patients (9,5%) had an
      early postoperative conductive disorder, 9 of them (4%) were definitively
      implanted after a mean delay of 31.8 days. Preoperative bifascicular bloc and
      early installation of postoperative high-grade conduction disturbances and its
      persistence for more than 48 hours are significantly associated with permanent
      postoperative conductive disorders (respectively P = 0.04 and = 0.03). Aortic
      valve surgery and infective endocarditis were more frequent in the implanted
      group but the difference was not significant. CONCLUSION: After open-heart
      valvular surgery; predictive factors of definitive conductive troubles justify an
      earlier pacemaker implantation. This attitude may accelerate the hospital
      discharge and decrease the disease cost effectiveness.

PMID- 16792030
TI  - [Percutaneous cardiac valve replacement: a review].
AB  - Surgery is no longer the only technique to replace a cardiac valve. New
      percutaneous procedures allow aortic or pulmonary valve implantation. Even if the
      feasibility of these procedures has been proved, cases reported are very rare and
      selected. This emergent technology is still at an early stage of development and
      new prospective studies will be necessary to evaluate these procedures correctly
      before concluding their clinical benefit. At this time surgery remains the gold
      standard in terms of cardiac valve replacement.

PMID- 16792032
TI  - [Percutaneous mitral commissurotomy and Lutembacher syndrome].
AB  - INTRODUCTION: Lutembacher syndrome refers to the rare combination of congenital
      atrial septal defect and acquired mitral stenosis. This condition is usually
      treated surgically by mitral valve operation with concomitant closure of the
      atrial septal defect. MATERIALS AND METHODS: Between 1993 and 2003, 4 patients
      with congenital Lutembacher syndrome had percutaneous mitral commissurotomy
      without closure of the atrial septal defect at our institution. The 4 patients
      were very symptomatic with right-sided heart failure signs and NYHA functional
      class III-IV. RESULTS: The procedure was carried out successfully for the four
      patients. Mitral valve area increased from 0.87 to 1.97 cm2 at mean; left atrial
      pressure decreased from 28.2 to 12.7 mmHg and the mean valve mitral gradient was
      reduced from 15.5 to 3.9 mmHg. Functional and clinical improvement was observed
      in all the cases. During a mean follow up of 55 +/- 29 months, our 4 patients
      remain pauci symptomatic under medical treatment. CONCLUSION: The percutaneous
      treatment of the Lutembacher syndrome is currently a possible alternative to the
      surgery among patients having an anatomy favourable to the procedure.

PMID- 16792031
TI  - [Percutaneous mitral commisurotomy in patients aged 60 years and more].
AB  - Of 745 patients treated by balloon mitral commissurotomy (BMC) between February
      1988 and December 2002, 45 were > or = 60-years old. Immediate and late outcomes
      in this group (group 1) were compared with those in the patients aged < 60-years
      (group 2). Baseline hemodynamic parameters were comparable in the two groups.
      Mitral surface area and hemodynamic parameters improved significantly after BMC
      in group 1: mean left atrial pressure fell from 18.76 +/- 6.18 to 10.65 +/- 4.38
      mmHg (P < 0.001), mean transmitral gradient from 11.03 +/- 4.70 to 4.63 +/- 2.05
      mmHg (p < 0.001) and mitral valve area from 0.99 +/- 0.22 to 1.88 +/- 0.41 cm2 (p
      < 0.001). Similar significant improvements were seen in group 2. The hemodynamic
      result was good in 69% of group 1 patients. Tamponade occurred in one patient.
      Mitral regurgitation grade I or II developed in 8 patients and remained stable in
      13 patients. These complication rates were comparable to those seen in group 2.
      In the group 1, a good result was maintained in 60% of patients after 43 +/- 23
      months of follow-up. Although restenosis was observed in 40% of patients,
      functional amelioration was obtained in most of cases. In the group 2, restenosis
      was observed in 25% of patients. The data from this study suggest that BMC is
      effective first therapy in patients aged > or = 60-years with symptomatic mitral
      stenosis.

PMID- 16792033
TI  - [Brucella endocardititis: clinical particularities and therapeutic modalities].
AB  - Brucella infective endocarditis is an uncommon, but serious complication of
      brucellosis. The aortic valve is the most commonly affected cardiac valve. Due to
      characteristics of the infection, medical therapy alone is not sufficient in
      treating the disease and best results are obtained with surgery combination. We
      describe a case of Brucella endocarditis involving the aortic valve suspected in
      front of the clinical data and the results of serology, confirmed by the culture
      of the native valves. In association with the medical treatment, management valve
      replacement lead to a favorable medium-term evolution.

PMID- 16792034
TI  - Sinus arrest and moderate hyperkalemia.
AB  - Hyperkalemia, especially if severe, is a frequent cause of cardiac rhythm
      pathologies. Sinus arrest of sudden onset is more likely to occur when the
      potassium level is very high (e.g. > 8 mmol/l) but in concomitance with negative
      chronotropic drugs it may occur even in presence of a moderate hyperkalemia. This
      case report highlights the fact that these kinds of drugs, especially in
      combination, are probably to be avoided in patients at risk of developing
      hyperkalemia (e.g. diabetics, renal failure, etc.), even of moderate degree,
      considering this life-threatening cardiac complication.

PMID- 16792035
TI  - [Cardiac asystole during acute anterior myocardial infarction: a consequence of
      endocardiac reflexes].
AB  - The authors report a case of paroxysmal, complete atrioventricular block during
      an anterior acute myocardial infarction, leading to asystolia. The different
      possible physiopathological mechanisms are discussed, suggesting a paroxysmal
      nodal conduction defect, secondary to transient parasympathetic stimulation,
      triggered by a Bezold-Jarish type of cardiac reflex. This reflex is frequently
      involved in various pathologic situations or diagnostic procedures, usual in
      cardiology. Although it is frequently observed in inferior myocardial infarction,
      it can occur during an anterior acute myocardial infarction.

PMID- 16792036
TI  - [Heart rate variability: variable values].

PMID- 16792041
TI  - [Anatomy and physiology of the nervous system].

PMID- 16792042
TI  - [Principal nervous disorders].

PMID- 16792043
TI  - [The nurse and management of the bedridden patient].

PMID- 16792044
TI  - [Some neurological examinations].

PMID- 16792045
TI  - [Pre-dialysis nursing consultation. Interview by Sylvie Warnet].

PMID- 16792046
TI  - [Patients with stomas].

PMID- 16792047
TI  - [Management of multiresistant bacteria].

PMID- 16792048
TI  - [Professional burnout in nurses].

PMID- 16792049
TI  - [Zolpidem].

PMID- 16792050
TI  - [Magnetic resonance imaging].

PMID- 16792051
TI  - [Oral mucosal lesions diagnosed in a stomatology service. An examination of
      clinico-pathological findings from the year 2003].
AB  - During 2003, a total of 258 new patients with oral soft tissue lesions were
      admitted at the Stomatology Service of the Department of Oral Surgery and
      Stomatology at the University of Berne. For the present study, 185 patients with
      clinically and histopathologically verified diagnoses were included. The
      following data was collected: prevalence of oral mucosal lesions, distribution of
      benign, precancerous and malign lesions in different age groups, and the
      concordance of the referral with the working diagnosis at the Stomatology
      Service. The most frequent pathological soft tissue findings were fibrous
      hyperplasias (n = 44) and oral lichen planus (n = 30). Precancerous lesions were
      present in 41 cases (30 patients with oral lichen planus, eleven oral
      leukoplakias), and ten patients had oral malignomas. Most lesions were found in
      patients between the age of 40 and 60 years. The referral diagnosis concurred in
      36.6% (n = 67) of the cases with the definite diagnosis before initiation of
      treatment, the working diagnosis in 70% (n = 128) of the cases. Therefore, it can
      be concluded that a specialised Stomatology Service serves as a center of
      competence due to large numbers of patients/cases seen and treated, and the
      resulting high level of clinical experience of the staff. Moreover, it is
      important in the primary diagnosis of oral squamous cell carcinoma, in
      collaboration with the referring dentist in private practice.

PMID- 16792052
TI  - Chlorhexidine-containing chewing gum. Clinical documentation.
AB  - A clinical documentation on chlorhexidine containing chewing gum is presented on
      the occasion of the launch of CHewX, a chewing gum containing 5 mg of
      chlorhexidine diacetate in Switzerland. Following an overview on functional
      chewing gum, the mechanism of action of chlorhexidine (CHX), its toxicity and
      safety are summarized and a review of clinical studies performed with CHX
      containing chewing gum given. Indication, dosage, precautions and benefits of CHX
      chewing gum are described.

PMID- 16792053
TI  - [A quadrant-design trial of four therapeutic modalities in chronic moderate
      periodontitis].
AB  - This randomized clinical study (blind and controlled) compared the effectiveness
      of an ER:YAG laser (combined with a calculus detection system using fluorescence
      induced by diode laser radiation for use in non-surgical periodontal therapy) as
      well as sonic and ultrasonic scalers and scaling and root planning with hand
      instruments to each other. 72 patients suffering from moderate chronic
      periodontitis (based on a probing depth of 4 mm or more of at least one tooth in
      each quadrant) were treated using either an Er:YAG-Laser (KEY 3, KaVo), a piezo
      electric ultrasonic system (Piezon Master 400, EMS), a sonic scaler (Sonicflex
      2003 L, KaVo), or Gracey Mini-five curettes (Hu Friedy) (control). These four
      kinds of treatment were randomized and grouped into quadrants. Oral health
      indicators, probing depths (PD) and clinical attachment levels were examined
      before commencement of the hygiene phase as well as three months after by a
      blind, calibrated examination. Within the study period, the mean PD (+/- SE) of
      the control group fell from 4.40 (0.03) mm to 3.08 (0.03) mm; for the laser
      group, the reduction was slightly greater, falling from 4.47 (0.04) mm to 3.08
      (0.03). In comparison, values for the ultrasonic group were 4.39 (0.04) mm in the
      pre-study examination and 3.09 (0.04) after treatment; in the sonic group, the
      values were 4.40 (0.03) mm pre-study and 3.07 (0.03) mm post-study. Within the
      control group, the mean CAL (+/- SE) decreased from 4.95 (0.07) mm to 3.92 (0.07)
      mm. Within the laser group, the reduction was more distinct, falling from 5.05
      (0.07) mm to 3.88 (0.07) mm. In the ultrasonic group, the median CAL decreased
      from 5.02 (0.08) mm to 3.88 (0.08) mm and from 4.95 (0.07) mm to 3.84 (0.08) mm
      within the sonic group. From the date of treatment until the third month
      thereafter, all of the clinical parameters were shown to be statistically
      significant (p < 0.0001; GEE). Use of the laser led to a much greater reduction
      in PD levels (p = 0.0021; GEE) than in the ultrasonic group and demonstrated a
      higher increase in CAL (p = 0.0010; GEE) relative to the manual methods.
      CONCLUSION: All four methods of treatment lead to a clinically comparable
      outcome.

PMID- 16792055
TI  - [Proliferative verrucous leukoplakia].
AB  - Proliferative verrucous leukoplakia (PVL) is a seldom form of oral leukoplakia
      (OL) with high transformation tendency. It starts as a bold hyperkeratosis
      changing into an exophytic verrucous form spreading in the oral cavity. The
      clinical diagnosis therefore is a retrospective one.

PMID- 16792054
TI  - [Preliminary clinical results of a prospective study of IPS e.max Press- and
      Cerec ProCAD- partial coverage crowns].
AB  - It was the aim of this prospective clinical splitmouth investigation to evaluate
      the survival rate and long-term behavior of all-ceramic partial coverage
      restorations (PCR) on molars. Pressed ceramic (IPS e.max Press) and CAD/CAM made
      (ProCAD) PCR were compared. 80 vital molars of 25 patients were restored with all
      ceramic PCR (40 IPS e.max Press* and 40 ProCAD*). All PCR were adhesively luted
      with a light-polymerizing composite (Syntac*/Tetric*) (*Ivoclar-Vivadent AG,
      Schaan, Liechtenstein). The ProCAD PCR were produced with Cerec 3 and Cerec Inlab
      CAD/CAM system (Sirona Dental Systems, Bensheim, Germany). IPS e.max Press PCR
      were heat-pressed following the lost-wax IPS-Empress method. Clinical recall was
      arranged in average 8, 14, 20 and 28 months after cementation of the restoration.
      PCR were classified by USPHS criteria. The prospective survival rate of ProCAD
      PCR was 97% and 100% for IPS e.max Press PCR after an observation period of 24
      months. After fracture, one ProCAD restoration had to be replaced after nine
      months. The clinical accuracy of the marginal fit of ProCAD PCR and IPS e.max
      Press PCR was recorded "Alfa". Limitations were recognized with respect to the
      color matching of both types of PCR ("Bravo"). CONCLUSION: Within the limits of
      the present clinical results, the tested all-ceramic materials IPS e.max Press
      und ProCAD seem to be indicated for partial coverage restorations on molars.

PMID- 16792056
TI  - [Alveolar ridge atrophy. The free vascularized fibular flap as alternative
      treatment in severe alveolar atrophy].
AB  - Implant-supported overdentures are the goal of treatment of the edentulous
      atrophic jaw. To gain adequate height there is in some instances need for
      additional bone augmentation. Ridge augmentation using a free vascularised
      fibular flap is one of the newer techniques. Prefabrication of fibular flaps, as
      described in this article, is a two-stage procedure to overcome the problems of
      osseointegration and missing attached gingiva. Accurate pre-operative 3-D-model
      planning, implant placement and vestibuloplasty in the first stage allow for
      occlusion driven reconstruction and immediate function in the second stage after
      a delay of six weeks. Based on our clinical experience the technique and the
      results are discussed.

PMID- 16792057
TI  - Determination of aflatoxin B1 in medical herbs: interlaboratory study.
AB  - A method was developed for the determination of aflatoxin B1 in medical herbs
      (senna pods, botanical name Cassia angustifolia; devil's claw, botanical name
      Harpagophytum procumbens; and ginger roots, botanical name Zingiber officinale).
      The method, which was tested in a mini-collaborative study by 4 laboratories, is
      based on an immunoaffinity cleanup followed by reversed-phase high-performance
      liquid chromatography separation and fluorescence detection after post-column
      derivatization. It allows the quantitation of aflatoxin B1 at levels lower than 2
      ng/g. A second extractant (acetone-water) was tested and compared to the proposed
      methanol-water extractant. Several post-column derivatization options
      (electrochemically generated bromine, photochemical reaction, and chemical
      bromination) as well as different integration modes (height versus area) were
      also investigated. No differences were found depending on the choice of
      derivatization system or the signal integration mode used. The method was tested
      for 3 different matrixes: senna pods, ginger root, and devil's claw. Performance
      characteristics were established from the results of the study and resulted in
      HorRat values ranging from 0.12 to 0.75 with mean recoveries from 78 to 91% for
      the extraction with methanol-water and HorRat values ranging from 0.10-1.03 with
      mean recoveries from 98 to 103% for the extraction with acetone-water. As a
      result, the method, with all tested variations, was found to be fit-for-purpose
      for the determination of aflatoxin B1 in medical herbs at levels of 1 microg/kg
      and above.

PMID- 16792058
TI  - Determination of the appetite suppressant P57 in Hoodia gordonii plant extracts
      and dietary supplements by liquid chromatography/electrospray ionization mass
      spectrometry (LC-MSD-TOF) and LC-UV methods.
AB  - Hoodia gordonii is traditionally used in South Africa for its appetite
      suppressant properties. P57AS3 (P57), an oxypregnane steroidal glycoside, is the
      only reported active constituent from this plant as an appetite suppressant.
      Effective quality control of these extracts or products requires rapid methods to
      determine P57 content. New methods of liquid chromatography/mass spectrometry
      (LC/MS) and LC-UV for analysis of P57 from H. gordonii have been developed. The
      quantitative determination of P57 was achieved with a Phenomenex Gemini
      (Torrance, CA) reversed-phase column using gradient mobile phase of water and
      acetonitrile, both containing 0.1% acetic acid. The method was validated for
      linearity, repeatability, and limits of detection and quantification. Good
      results were obtained in terms of repeatability (relative standard deviation
      <5.0%) and recovery (98.5-103.5%). The developed methods were applied to the
      determination of P57 for H. gordonii plant samples, one related genus (Opuntia
      ficus-indica), and dietary supplements that claim to contain H. gordonii.

PMID- 16792059
TI  - Development and validation of a high-throughput based on liquid chromatography
      with ultraviolet absorption and mass spectrometry detection method for
      quantitation of cichoric acid in Echinacea purpurea aerial-based dietary
      supplements.
AB  - A new, rapid, and reproducible reversed-phased liquid chromatography (LC) method
      with ultraviolet (UV) absorption and/or mass spectrometry (MS) detection has been
      developed and validated for quantitation of cichoric acid, a major constituent of
      Echinacea spp. The method involves the use of a short Phenomenex Hydro-RP C18
      column (4 microm, 50 mm x 3.0 mm id) and a simple isocratic mobile phase profile.
      Both UV (diode array detector) and selective-ion monitoring (SIM) at m/z 472.8
      were used for quantitation of cichoric acid. The limit of detection was 0.75 ng
      for UV and 0.15 ng for MS-SIM, and the limit of quantitation was is 2.5 ng for UV
      and 0.5 ng for MS-SIM. Water-methanol (1 + 1) soluble extracts of 6 commercially
      available Echinacea purpurea aerial parts-based dietary supplements (EPADS).
      EPADS were first profiled using a traditional HPLC-UV method. Their UV
      chromatograms were compared, and cichoric acid was identified to be a key
      biomarker for EPADS. Then the samples were analyzed by the fast LC-UV/MS method.
      The turnaround time for a single analysis was 3 min, compared to 15 to 60 min
      needed for traditional reported LC methods. The high-throughput method was able
      to separate the cichoric acid peak from peaks of other components in extracts of
      complex matrixes of EPADS.

PMID- 16792060
TI  - High-performance thin-layer chromatography densitometric method for simultaneous
      quantitation of phyllanthin, hypophyllanthin, gallic acid, and ellagic acid in
      Phyllanthus amarus.
AB  - Whole plant of Phyllanthus amarus Linn. is a reputed drug of the Indian systems
      of medicine that is used as hepatoprotective agent. A simple high-performance
      thin-layer chromatography (HPTLC) densitometric method has been developed for the
      simultaneous quantitation of phyllanthin, hypophyllanthin, gallic acid, and
      ellagic acid in the whole plant of P. amarus. They were found at levels of 0.37,
      1.16, 0.36, and 0.17% (w/w), respectively. The method was validated for
      precision, repeatability, and accuracy. Instrumental precision was found to be
      0.54, 0.93, 0.08, and 0.78% (coefficient of variation, CV); repeatability of the
      method was 1.01, 0.79, 0.98, and 1.06% (CV) for phyllanthin, hypophyllanthin,
      gallic acid, and ellagic acid, respectively. Accuracy of the method was
      determined by a recovery study conducted at 3 different levels, and the average
      recovery was found to be 99.09% for phyllanthin, 99.27% for hypophyllanthin,
      98.69% for gallic acid, and 100.49% for ellagic acid. The proposed HPTLC method
      was found to be simple, precise, specific, sensitive, and accurate and can be
      used for routine quality control of raw material of P. amarus and formulations
      containing P. amarus. It also has the applicability in quantitating any of these
      marker compounds in other drugs.

PMID- 16792061
TI  - Determination of aflatoxins and ochratoxin A in ginseng and other botanical roots
      by immunoaffinity column cleanup and liquid chromatography with fluorescence
      detection.
AB  - Mycotoxins are toxic secondary metabolites produced by certain molds and are
      common contaminants of many important food crops, such as grains, nuts, and
      spices. Some mycotoxins are found in fruits, vegetables, and botanical roots.
      These contaminants have a broad range of toxic effects, including
      carcinogenicity, immunotoxicity, neurotoxicity, and reproductive and
      developmental toxicity. The public health concerns related to both acute and
      chronic effects of mycotoxins in animals have prompted more than 100 countries to
      establish regulatory limits for some of the well-known mycotoxins, such as the
      aflatoxins (AFL). Our research focused on method development for 2 of these
      toxins, AFL and ochratoxin A (OTA), in ginseng and other selected botanical
      roots. Methods using an immunoaffinity column (IAC) cleanup, liquid
      chromatographic separation, and fluorescence detection were modified and
      evaluated. Two types of IAC cleanup were evaluated: IAC for AFL, and IAC for both
      AFL and OTA. Three derivatization techniques to enhance the fluorescence of the
      AFL were compared: precolumn trifluoroacetic acid, postcolumn bromination, and
      postcolumn ultraviolet irradiation. No derivatization was needed for OTA. Results
      for AFL using the single analyte IAC cleanup and the 3 derivatization techniques
      were all comparable for ginseng and for other roots such as ginger, licorice, and
      kava-kava. Recoveries of added AFL for ginseng at levels from 2 to 16 ng/g were
      about 80%. Using IAC cleanup for both AFL and OTA recoveries of added AFL for
      ginseng at 4-16 ng/g were about 70%, and for ginger, licorice, and kava-kava were
      about 60%. Recoveries of added OTA for ginseng, ginger, and echinacea at 4 ng/g
      were about 55%.

PMID- 16792062
TI  - Spectrophotometric determination of acyclovir and ribavirin in their dosage
      forms.
AB  - Two simple, accurate, and reliable spectrophotometric methods have been developed
      for the determination of 2 antiviral drugs, acyclovir (ACV) and ribavirin (RBV),
      in their pharmaceutical formulations. These methods are based on oxidation of the
      2 drugs with either cerium (IV) ammonium sulfate (Method A) or potassium
      persulfate (Method B). The products of oxidation in both methods are coupled with
      3-methylbenzothiazolin 2-one hydrazone, producing a deep blue color with a
      maximum absorption wavelength at 630 nm. In Method A, the absorbance
      concentration plots were linear over the ranges of 5-50 and 10-60 microg/mL with
      detection limits of 0.18 microg/mL (8 x 10(-7) M) and 0.63 microg/mL (2.58 x 10(
      6) M) for ACV and RBV, respectively. In Method B, the ranges were 5-45 and 20-50
      microg/mL with detection limits of 0.11 microg/mL (4.88 x 10(-7) M) and 1.40
      microg/mL (5.73 x 10(-6) M) for the 2 drugs, respectively. The molar
      absorptivities were 4.1 x 10(3) and 3.65 x 10(3) L/mol/cm in Method A and 5.03 x
      10(3) and 3.97 x 10(3) L/mol/cm in Method B for the 2 drugs, respectively. The
      proposed methods were applied successfully for the determination of the 2 drugs
      in their pharmaceutical formulations. The percentage recoveries +/- standard
      deviation were 99.57 +/- 0.86 and 100.82 +/- 0.46 for ACV; 99.41 +/- 1.08 and
      100.35 +/- 1.03 for RBV. The results obtained were compared statistically with
      those given by official methods and showed no significant differences regarding
      accuracy and precision.

PMID- 16792063
TI  - Determination of gatifloxacin in bulk and tablet preparations by high-performance
      liquid chromatography.
AB  - A sensitive, precise, and specific high-performance liquid chromatographic (HPLC)
      method was developed for the assay of gatifloxacin (GATX) in raw material and
      tablets. The method validation parameters yielded good results and included the
      range, linearity, precision, accuracy, specificity, and recovery. It was also
      found that the excipients in the commercial tablet preparation did not interfere
      with the assay. The HPLC separation was carried out by reversed-phase
      chromatography on a C18 absorbosphere column (250 x 4.6 mm id, 5 microm particle
      size) with a mobile phase composed of acetic acid 5%-acetonitrile-methanol (70 +
      15 + 15, v/v/v) pumped isocratically at a flow rate of 1.0 mL/min. The effluent
      was monitored at 287 nm. The calibration graph for GATX was linear from 4.0 to
      14.0 microg/mL. The interday and intraday precisions (relative standard
      deviation) were less than 1.05%.

PMID- 16792064
TI  - Utilization of 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) for kinetic
      spectrophotometric assay of befunolol hydrochloride in its pharmaceutical
      formulation.
AB  - A simple, accurate, precise, and sensitive kinetic spectrophotometric method for
      determination of befunolol hydrochloride is described. The method is based on the
      formation of a colored product with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD
      Cl) in methanol at 70 degrees C for 45 min. The red-colored product was measured
      at 523 nm. The optimization of various experimental conditions is described;
      Beer's law was obeyed in the range 15.25 x 10(-6) to 122.04 x 10(-6) M. The
      results obtained showed good recoveries (100.1 +/- 0.80%). Application of the
      proposed method to a pharmaceutical formulation was successfully achieved. The
      determination of befunolol hydrochloride by fixed time, fixed concentration, and
      rate constant methods was feasible with the calibration equation obtained.
      However, the fixed time method proved to be more applicable.

PMID- 16792065
TI  - Validation of a microwell DNA probe assay for detection of Listeria spp. in foods
      Performance-tested method 010403.
AB  - A new DNA hybridization assay in microwell format for detection of Listeria spp.
      in foods and environmental samples was developed. This assay uses Listeria
      specific oligonucleotide probes labeled with horseradish peroxidase and a
      photometrically determined end point. Validation studies with 15 different food
      commodities and a variety of environmental sample types were conducted to compare
      the performance of this alternative test versus reference methods. Meats,
      seafood, dairy products, and vegetables comprised the categories of food tested.
      Food samples were inoculated at 2 levels and refrigerated or frozen for at least
      72 h. Uninoculated (negative) control samples were included in each trial.
      Samples were enriched according to the procedure recommended by either the U.S.
      Food and Drug Administration (FDA) or the U.S. Department of Agriculture (USDA),
      Food Safety and Inspection Service (FSIS). Samples enriched for 24 h were
      transferred to Oxford agar plates and incubated for 24 h. The surface of the
      plates was then swabbed and any growth present was transferred to phosphate
      buffer solution for the performance of the DNA assay. A standard confirmation
      procedure was used to compare the number of positive samples obtained with the
      DNA method versus reference methods. Statistical analyses of the results indicate
      that the proposed alternative method performs equally to cultural reference
      methods. The DNA assay is able to detect as low as 1 colony-forming unit of
      Listeria in a 25 g food sample, with results available as early as 48 h after the
      start of sample enrichment.

PMID- 16792067
TI  - Liquid chromatographic analysis of aflatoxin using post-column photochemical
      derivatization: collaborative study.
AB  - Aflatoxin analysis, with post-column derivatization using a photochemical reactor
      for enhanced detection (PHRED) system for derivatization, has been compared to
      the officially recognized iodine and Kobra cell derivatization systems. This
      photochemical system has been extensively used for screening peanuts by some U.S.
      Department of Agriculture laboratories for many years. From their periodic method
      checks, using standard spiked samples, an 80 sample series with each of the 3
      derivatization methods was statistically analyzed. Paired comparisons, using the
      same sample extract, were also made between the PHRED and one of the other 2
      methods, among laboratories in 4 different countries, on a variety of naturally
      contaminated commodity products. The differences between the techniques were not
      significant for peanuts, but for corn the photochemical system consistently gave
      slightly higher values for aflatoxins B1 and B2 than the Kobra cell method.
      However, a comparison of all sample results showed no significant differences
      between methods. The Pearson correlation coefficients for aflatoxin B1 in 102
      test samples and aflatoxin B2 in 94 test samples were 0.9994 and 0.9874,
      respectively. The probability factor was P < 0.0001, and the t-tests were not
      significantly different except for the corn. These indicated that the PHRED
      system is equivalent to the iodine and Kobra cell methods for peanuts relative to
      the current official procedures, but the PHRED system has a slightly high bias
      for corn compared to the iodine and Kobra cell systems.

PMID- 16792066
TI  - Synchronous analysis method for detection of citrinin and the lactone and acid
      forms of monacolin K in red mold rice.
AB  - The Monascus product known as red mold rice (RMR) has been found to contain the
      cholesterol-lowering agent monacolin K (MK), including the lactone form (MKL) and
      the acid form (MKA) and mycotoxin citrinin (CT). In current studies, CT and MK
      are usually detected by different analysis methods, which have a high level of
      error, and are inconvenient, expensive, and time-consuming. The goal of this
      study is to establish a rapid synchronous analysis method for the detection of
      CT, MKL, and MKA levels in RMR. In this study, CT, MKL, and MKA are extracted by
      the same extraction method and are then separated in a reversed-phase high
      performance liquid chromatography (HPLC) C18 column. The elution from the C18
      column is then passed through an ultraviolet detector and introduced directly
      into the fluorescence detector. The results show that higher recovery rates of
      CT, MKL, and MLK are yielded from RMR powder by extracting with 95% ethanol (10
      mL) at 60 degrees C for 30 min. Regarding the optimal conditions of HPLC, the
      peaks of CT, MKL, and MKA can be clearly separated from any noise peaks by
      isocratic elution with optimum mobile phase, acetonitrile-water-trifluoroacetate
      (55 + 45 + 0.05, v/v).

PMID- 16792068
TI  - Detection of genetic modification in cured tobacco leaf: proficiency testing
      using polymerase chain reaction-based methods.
AB  - The Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA;
      Paris, France) "Task Force Genetically Modified Tobacco-Detection Methods"
      investigated the performance of qualitative and quantitative methods based on the
      polymerase chain reaction (PCR) for the detection and quantitation of genetically
      modified (GM) tobacco. In the 4 successful rounds of proficiency testing, the
      cauliflower mosaic virus 35S RNA promoter (CaMV 35S) and the Agrobacterium
      tumefaciens nopaline synthase terminator (NOS) were selected as target sequences.
      Blind-coded reference materials containing from 0.1 to 5.0% and from 0.15 to 4%
      GM tobacco were used in 2 rounds of qualitative and quantitative PCR,
      respectively. Eighteen laboratories from 10 countries participated in this study.
      Considering all methods and 2 rounds, the different laboratories were able to
      detect GM tobacco at the 0.1% level in 46 out of 58 tests in qualitative assays.
      The results of the proficiency test indicate that both end point screening and
      real-time quantitative methods are suitable for the detection of genetically
      modified organisms in tobacco leaf samples having a GM content of 0.1% or higher.
      The CORESTA proficiency study represents a first step towards the interlaboratory
      evaluation of accuracy and precision of PCR-based GM tobacco detection, which may
      lead to the harmonization of analytical procedures and to the enhancement of
      comparability of testing results produced by different laboratories.

PMID- 16792069
TI  - Multiplex-polymerase chain reaction assay for the authentication of the mackerel
      Scomber colias in commercial canned products.
AB  - A multiplex-polymerase chain reaction (PCR) system was developed for the
      authentication of the mackerel Scomber colias in commercial canned products. This
      novel method consists of an S. colias-specific fragment [159 base pairs (bp)]
      located in the nontranscribed spacer (NTS) sequence, and a Scomber genus-specific
      PCR product in the 5S rRNA gene (196-201 bp) as a positive amplification control.
      The system was assayed using 18 different canned products labeled as S. colias. A
      positive identification was made in all but one sample, revealing this
      methodology as a potential molecular tool for direct application in the
      authentication of S. colias canned products.

PMID- 16792070
TI  - Determination of nitrite, nitrate, and glucose-6-phosphate in muscle tissues and
      cured meat by IC/MS.
AB  - The endogenous nitrate concentration in fresh meat and the residual nitrate and
      nitrite contents after curing are related to food quality and safety. Most ion
      chromatography (IC) methods suffer from interferences, especially in fresh meat
      samples, in which the endogenous nitrate content is low, and in cured meat
      products, in which other nitrogenous compounds can interfere with the separation
      of inorganic anions. One of the major classes of interfering compounds in fresh
      meat are sugar phosphates, which originate from glycolysis during the conversion
      of muscle glycogen to lactic acid. Nitrate can be separated from interfering
      compounds with a high-capacity anion-exchange column that was manufactured for
      use with hydroxide eluents (i.e., hydroxide-selective). This column has a
      different selectivity than traditional IC columns that use carbonate eluents and
      facilitates the determination of nitrate in both fresh and cured meats. Nitrate
      was detected by both suppressed conductivity measurement and mass spectrometry
      (MS). The identifications of nitrate and glucose-6-phosphate were confirmed by MS
      detection. The described IC/MS method is robust, sensitive to nitrate
      concentrations as low as 0.10 mg/kg, and can determine sugar phosphates that are
      useful for monitoring meat freshness. We successfully used this method to
      determine nitrate in nearly 100 muscle tissues and cured meat samples.

PMID- 16792071
TI  - Evaluation of a preclinical blood test for scrapie in sheep using immunocapillary
      electrophoresis.
AB  - An analytical method is described for detection of endogenous disease-associated
      prion protein in the buffy coat fraction from the blood of sheep infected with
      scrapie. The method has been improved and evaluated for its performance in the
      preclinical diagnosis of ovine transmissible spongiform encephalopathies. The
      test system uses a protocol for sample preparation that includes extraction and
      concentration and a test method that uses a liquid-phase competitive immunoassay
      for prion protein. Antibodies directed to a peptide sequence at the C-terminus of
      the prion protein (PrP) and a fluorescein-labeled peptide conjugate are used in
      the assay. Free zone capillary electrophoresis with laser-induced fluorescence
      for detection is used to separate the antibody-bound fluorescently labeled
      peptide and free labeled peptide. In this assay, the PrP competes with the
      fluorescently labeled peptide for limited antibody binding sites, which results
      in a reduction of the peak representing the immunocomplex of the antibody bound
      to the fluorescently labeled peptide. When blood samples from scrapie-infected
      sheep aged 7-12 months and of the scrapie-susceptible PrP genotypes VRQ/VRQ and
      VRQ/ARQ were analyzed, the abnormal PrP was found in blood samples. These results
      correlated with the post-mortem diagnosis of scrapie. The sheep were preclinical
      and appeared normal at the time of testing but later died with clinical disease
      approximately 12 months after testing. In older animals, and those with clinical
      signs, a smaller percentage of animals tested positive. This study has
      demonstrated that this technology can be used as a sensitive, rapid preclinical
      test to detect the disease-associated PrP in the blood of scrapie-infected sheep.
      Improvements in the extraction protocol and capillary electrophoresis conditions
      will enhance the robustness of this test.

PMID- 16792072
TI  - Determination of semicarbazide in baby food by liquid chromatography/tandem mass
      spectrometry: interlaboratory validation study.
AB  - An interlaboratory validation study funded by the European Commission,
      Directorate General for Health and Consumer Protection (DG SANCO), was conducted
      to evaluate the effectiveness of a liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) method for the determination of semicarbazide (SEM) in different types
      of baby food at a possible future European regulatory limit (10 ng/g). The test
      portion of the sample was extracted with hydrochloric acid, and the analyte was
      derivatized with 2-nitrobenzaldehyde, with 1,2-[15N2, 13C] SEM as an internal
      standard. The extract was neutralized and then purified on a solid-phase
      extraction cartridge. The SEM was determined by reversed-phase LC with detection
      by MS/MS. Apple puree, rice pudding, and meat/vegetable meal baby food materials,
      spiked with SEM at levels of about 3, 10, and 30 ng/g, respectively, were sent to
      20 laboratories in 12 different European countries, which submitted results from
      17 participants. Recoveries ranged from 88.8 to 106.1%. Based on results for
      spiked samples (blind pairs at 3 levels), the relative standard deviations for
      repeatability (RSDr) ranged from 4.2 to 6.9% and the relative standard deviations
      for reproducibility (RSDR) ranged from 16.6 to 24.3%. The method showed
      acceptable within- and between-laboratory precision for all 3 matrixes, as
      evidenced by HorRat values, at the target levels for the determination of SEM.

PMID- 16792073
TI  - Verification of a method for microcoulometric determination of adsorbable organic
      halide pollutants in natural, drinking, waste, and treated waters.
AB  - A microcoulometric method is described for the determination of organic-halide
      pollutants at 2-2000 microg/L in natural, drinking, waste, and treated waters.
      The conditions for the adsorption of organic halides, using a microcolumn with
      activated charcoal-and for the desorption of inorganic halides-as well as for the
      pyrolysis process, were optimized for the successful determination of priority
      organic halide pollutants. An appropriate criterion was proposed to stop the
      desorption step. The mean recovery was 100.3%, and the mean relative standard
      deviation was 9.9%. The detection limit based on 3 times the standard deviation
      of the blank sample was 2 microg/L.

PMID- 16792074
TI  - Determination of residues of 446 pesticides in fruits and vegetables by three
      cartridge solid-phase extraction-gas chromatography-mass spectrometry and liquid
      chromatography-tandem mass spectrometry.
AB  - A method was developed for determination of residues of 446 pesticides in fruits
      and vegetables through the use of cleanup by a 3-cartridge solid-phase extraction
      gas chromatography/ mass spectrometry (GC/MS) and liquid chromatography/tandem
      mass spectrometry (LC/MS/MS). Fruit and vegetable samples (20 g) were extracted
      with 40 mL acetonitrile, salted out, and centrifuged. Half of the supernatant was
      passed into an Envi-18 cartridge, eluted with acetonitrile, and cleaned up with
      Envi-Carb and aminopropyl Sep-Pak cartridges in series after concentration of the
      eluates. Pesticides were eluted with acetonitrile-toluene (3 + 1, v/v), and
      eluates were concentrated to 0.5 mL and then added into internal standards after
      solvent exchange with 2 mL hexane and used for determination of 383 pesticides by
      GC/MS. The other half of the supernatant was concentrated to 1 mL and cleaned up
      with Envi-Carb and aminopropyl Sep-Pak cartridges in series. Pesticides were
      eluted with acetonitrile-toluene (3 + 1, v/v), and the eluates were concentrated
      to 0.5 mL, dried with nitrogen gas, diluted to 1.0 mL with acetonitrile-water (3
      + 2, v/v), and used for determination of 63 pesticides by LC/MS/MS. The limit of
      detection for the method was 0.2-600 ng/g depending on the individual pesticide.
      In the method, fortification recovery tests at high, medium, and low levels were
      conducted on 6 varieties of fruits and vegetables, i.e., apples, oranges, grapes,
      cabbage, tomatoes, and celery, with average recoveries falling within the range
      of 55.0-133.8% for 446 pesticides, among which average recoveries between 60.0
      120.0% accounted for 99% of the results. The relative standard deviation was
      between 2.1-39.1%, of which a relative standard deviation of 2.1-25.0% made up
      96% of the results. Experiments proved that the method was applicable for
      determination of residues of 446 pesticides in fruit and vegetables.

PMID- 16792075
TI  - Method validation for determination of the 15 European-priority polycyclic
      aromatic hydrocarbons in primary smoke condensates by gas chromatography/mass
      spectrometry: interlaboratory study.
AB  - A collaborative study was conducted to validate an analytical method for
      quantification of the 15 polycyclic aromatic hydrocarbons (PAHs) regarded in 2002
      as a health concern by the former Scientific Committee on Food of the European
      Commission (SCF) in primary smoke condensates. The method is based on gas
      chromatography/mass spectrometry of a cyclohexane extract with solid-phase
      cleanup through silica gel. The analytes were detected in the selected-ion
      monitoring mode and quantified by using 3 isotopically labeled internal standard
      compounds. Seventeen laboratories participated in the collaborative validation
      study, of which 12 reported valid results. The data were subjected to Cochran,
      single Grubbs, and double Grubbs tests for statistical outliers. A maximum of 2
      outliers was eliminated before further statistical evaluation of the method
      performance characteristics. Depending on the analyte, the results showed
      relative standard deviations for repeatability between 4.2 and 30% and for
      reproducibility from 9.9 to 60%. The recoveries varied between about 50 and 85%,
      except those for cyclopenta[cd]pyrene, dibenzo[a,l]pyrene, and
      dibenzo[a,h]pyrene. Nevertheless, because Commission Directive 2005/10/EC allows
      for a recovery range of 50-120% for (BaP) benzo[a]pyrene in various foods, it can
      be concluded that the method performs appropriately within the analytical range
      between 5 and 25 microg/kg of primary smoke condensate. For BaP the validated
      analytical range covered 5-20 microg/kg, and for benzo[a]anthracene (BaA) 10-25
      microg/kg. The method is suitable for monitoring BaP and BaA at their respective
      maximum permitted levels of 10 and 20 microg/kg. Three analytes, benzo[b]-,
      benzo[j]-, and benzo[k]-fluoranthene could not be separated by all of the
      participants and were therefore treated as the sum. Nevertheless, with this
      method the pattern of the respective concentrations of these 15 PAHs can be
      monitored in primary smoke condensate as suggested by the SCF.

PMID- 16792076
TI  - Determination of magnesium in foods by single-sweep polarography.
AB  - In KOH, the Mg(II)-bromopyrogallol red (BPR) complex produced a very sensitive
      polarographic wave at -1.30 V. The wave height was linear with the concentration
      of Mg(II) in the range of 0.05 to 2 microg/mL. The detection limit was 0.01
      microg/mL. The electrochemical behavior of Mg(II)-BPR was studied by
      electrochemical and spectrophotometric methods. Experiments proved that the
      polarographic wave of Mg(II)-BPR was due to the reduction of BPR in the Mg(II)
      BPR complex. The method, which was sensitive, selective, and simple to perform,
      was used to determine magnesium in foods, and the results were consistent with
      those obtained by atomic absorption spectroscopy.

PMID- 16792077
TI  - Determination of deltamethrin residues in plant materials by liquid
      chromatography/tandem mass spectrometry with electrospray ionization.
AB  - This paper describes a selective and sensitive method that uses liquid
      chromatography/tandem mass spectrometry with positive electrospray ionization
      (ESI+) for the determination of deltamethrin in a variety of crops. Samples were
      extracted by conventional high-speed blending. Some samples required no further
      cleanup; others were cleaned up by gel permeation chromatography, strong cation
      exchange cartridges, or partitioning with n-hexane. In the determinative step,
      the buffered neutral mobile phase, consisting of 10 mM ammonium acetate (pH 6.8)
      and methanol, and ESI+ provided strong ammonium adduct formation to [M+NH4]+ at
      m/z 523, and the multiple-reaction monitoring (MRM) transition at m/z 523/281 was
      used for the quantitation of deltamethrin. A second MRM transition at m/z 525/283
      was used for confirmation. The limit of quantitation (LOQ) values were 0.01 mg/kg
      for edible materials and 0.05 mg/kg for nonedible materials. Mean overall
      recoveries at the LOQ and the 10-fold LOQ ranged from 73 to 96%, and the relative
      standard deviations were <10% for all samples materials analyzed.

PMID- 16792078
TI  - Biosensors: making sense of food.

PMID- 16792080
TI  - Vitamin and pseudovitamin analysis with biosensors in food products--a review.
AB  - Biosensors are becoming increasingly important in the food industry for
      application in safety and quality control among routinely used techniques such as
      microbiology, chromatography, or specific enzymatic methods. Biosensors offer
      advantages as alternatives to conventional methods because of their inherent
      specificity, simplicity, and rapid response. This article presents a short review
      of vitamin and pseudovitamin analysis techniques using biosensor technology as
      applied in the food industries, with particular attention to immobilization
      techniques of biorecognition elements, transducers, an overview of vitamin
      biosensors, and some future trends.

PMID- 16792079
TI  - Overview of affinity biosensors in food analysis.
AB  - The 4 major driving forces that are expected to lead to increased use of affinity
      biosensors that meet crucial industrial test specifications, e.g., fast,
      reliable, cost-effective, and use of low-skilled personnel, are (1) strict
      legislative framework, e.g., recent changes proposed to the European food safety
      and hygiene legislation, EC No. 178/2002; (2) industrial shift from quality
      control to quality assurance procedures, e.g., Hazard Analysis Critical Control
      Point, ensuring effective positioning in the global competitive trade; (3) just
      in-time production resulting in 'right' product every time; and (4) consumer
      demand for safe and wholesome products. The affinity biosensors field has
      expanded significantly over the past decade, with a projected global biosensors
      market growth from $6.1 billion in 2004 to $8.2 billion in 2009, representing
      major industrial sectors (e.g., Pharma, Medicare, and Food). This brief review is
      targeted to affinity biosensors developed for the food industry and includes
      research and development leading to biosensors for microbiological and chemical
      analytes of industrial concern, commercial biosensors products on the market, and
      examples of future prospects in this diagnostic field.

PMID- 16792081
TI  - Surface plasmon resonance biosensors for detection of pathogenic microorganisms:
      strategies to secure food and environmental safety.
AB  - This review describes the exploitation of exclusively optical surface plasmon
      resonance (SPR) biosensors for the direct and indirect detection of pathogenic
      microorganisms in food chains and the environment. Direct detection is, in most
      cases, facilitated by the use of defined monoclonal or polyclonal antibodies
      raised against (a part of) the target pathogenic microorganisms. The antibodies
      were immobilized to a solid phase of the sensor to capture the microbe from the
      sample. Alternatively, antibodies were used in an inhibition-like assay involving
      incubation with the target organism prior to analysis of nonbound antibodies. The
      free immunoglobins were screened on a sensor surface coated with either purified
      antigens or with Fc or Fab binding antibodies. Discussed examples of these
      approaches are the determination of Escherichia coli O1 57:H7, Salmonella spp.,
      and Listeria monocytogenes. Another direct detection strategy involved SPR
      analysis of polymerase chain reaction products of Shiga toxin-2 genes reporting
      the presence of E. coli O157:H7 in human stool. Metabolic products have been
      exploited as biomarkers for the presence of a microbial agent, such as
      enterotoxin B and a virulence factor for the occurrence of Staphylococcus aureus
      and Streptococcus suis, respectively. Indirect detection, on the other hand, is
      performed by analysis of a humoral immune response of the infected animal or
      human. By immobilization of specific antigenic structures, infections with Herpes
      simplex and human immunodeficiency viruses, Salmonella and Treponema pallidum
      bacteria, and Schistosoma spp. parasites were revealed using human, avian, and
      porcine sera and avian eggs. Bound antibodies were easily isotyped using an SPR
      biosensor to reveal the infection history of the individual. Discussed studies
      show the recent recognition of the suitability of this type of instrument for
      (rapid) detection of health-threatening microbes to food and environmental
      microbial safety.

PMID- 16792082
TI  - Biosensor analysis of beta-lactams in milk using the carboxypeptidase activity of
      a bacterial penicillin binding protein.
AB  - The applicability of a beta-lactam receptor protein for detection of beta-lactam
      antibiotics in milk using surface plasmon resonance (SPR) biosensor technology
      was investigated. The advantage of using a receptor protein instead of antibodies
      for detection of beta-lactams is that a generic assay, specific for the active
      form of the beta-lactam structure, is obtained. Two assays based on the enzymatic
      activity of the DD-carboxypeptidase from Actinomadura R39 were developed, using a
      Biacore SPR biosensor. The carboxypeptidase converts a tri-peptide into a di
      peptide, a reaction which is inhibited in the presence of beta-lactams.
      Polyclonal antibodies against the 2 peptides were developed and used to measure
      the amount of enzymatic product formed (di-peptide assay) or the amount of
      remaining enzymatic substrate (tri-peptide assay), respectively. The 2 assays
      showed similar performances with respect to detection limits (1.2 and 1.5
      microg/kg, respectively) and precision (coefficient of variation <5%) for
      penicillin G in milk. Several other beta-lactams were detected at or near their
      respective maximum residue limit. Furthermore, the 2 peptide assays were
      evaluated against 5 commercial kit tests in the screening of 195 producer milk
      samples. The biosensor assays showed 0% false-negative and 27% false-positive
      results, whereas the figures were 0% false-negative and 27-53% false-positive
      results for other screening tests investigated.

PMID- 16792083
TI  - Improvements to a surface plasmon resonance-based immunoassay for the steroid
      hormone progesterone.
AB  - The effects of modifications to an existing protocol for a surface plasmon
      resonance biosensor-based inhibition immunoassay for progesterone in cow's milk
      with a sensitivity of 3.5 ng/mL were examined to establish if the detection limit
      could be further reduced to broaden the potential applications of the assay. The
      mean relative standard deviation of duplicate measurements was 0.62% and the high
      precision resulted in very low values for the lower detection limits. Hence, the
      standard concentrations giving 95% maximum binding [effective dose (ED 95)] were
      compared instead. The ED 95 was not affected within a running temperature range
      of 20-37 degrees C, or at a flow rate and a contact time above 20 microL/min and
      90 s, respectively. Increasing both the absolute sample volume and the antibody
      dilution improved sensitivity. However, there was a simultaneous reduction in the
      working range when the assay was applied to milk due to nonspecific binding. Less
      antibody was associated with large decreases in the maximum binding, but because
      the high precision extended over a broad analytical range, an ED 95 of 0.4-0.6
      ng/mL in milk and 35-60 pg/mL in HBS-EP buffer were achieved. Thus, simple
      procedural modifications with the same sensor chip can alter performance
      characteristics of the assay as required for different applications.

PMID- 16792084
TI  - Quantification of proteins in dairy products using an optical biosensor.
AB  - Two recent techniques using optical immunosensor technology were developed for
      the quantification of milk proteins in dairy products. The first application is
      the simultaneous quantification of the 3 major caseins (alpha(s1), beta, and
      kappa). This assay consists of a 2-step sandwich strategy, with 2 monoclonal
      antibodies directed against the N- and C-terminal extremities of each of the
      caseins, respectively. This strategy permits only intact caseins to be
      quantified, and not their degradation products. The technique is fast (10 min),
      sensitive (detection limit about 0.87 microg/mL), and has been applied
      successfully to raw and drinking milks. In the second application, the severity
      of the heat treatment sustained by a milk of unknown origin is determined by
      quantifying separately the native and heat-denatured forms of alpha-lactalbumin
      with specific monoclonal antibodies. The technique allows discrimination of the
      different heat treatments studied (pasteurization, direct and indirect ultra-high
      temperature, sterilization), is fast (4 min), repeatable, fully automated, and
      requires no pretreatment of the milk sample.

PMID- 16792085
TI  - Spreeta-based biosensor immunoassays to detect fraudulent adulteration in milk
      and milk powder.
AB  - Biacore biosensors (Biacore AB, Uppsala, Sweden) have proven to be robust
      analytical tools for the automated immunochemical detection of different
      adulterants and contaminants in milk and milk powder. However, the significant
      cost of the instruments is a disincentive for their wide application in food
      control laboratories. Therefore, a low-cost alternative optical biosensor
      (Spreeta, Texas Instruments, Attleboro, MA) was built into an affordable liquid
      handling system. Using this prototype biosensor, an inhibition immunoassay for
      bovine K-casein was evaluated for the detection of cow's milk in ewe's and goat's
      milk and for the detection of bovine rennet whey powder in milk powder.
      Comparable sensitivities were obtained for both adulterants in the Spreeta-based
      prototype biosensor and a Biacore 3000 instrument. The limit of detection for
      cow's milk was 0.17% (v/v) and bovine rennet whey powder could be detected in
      milk powder above 1% (w/w). The Spreeta sensor was also useful in the control of
      fraudulent water additions to milk, simply by measuring differences in the bulk
      response.

PMID- 16792086
TI  - Food allergen detection with biosensor immunoassays.
AB  - An optical biosensor was used to develop both direct and sandwich immunoassays
      for the detection of proteins from milk, egg, hazelnut, peanut, shellfish, and
      sesame in food samples. Affinity-purified polyclonal antibodies raised against
      the proteins were immobilized on the biosensor chip. Food samples were injected
      and the proteins that bound to the antibodies on the surface were detected by a
      shift in the resonance angle. By adding a second antibody in a sandwich assay,
      matrix effects could be overcome and the sensitivity and selectivity enhanced.
      Detection of allergen levels down to 1-12.5 microg/g in food samples was
      demonstrated for the various assays. Good agreement of results was also obtained
      from parallel analysis with alternative immunoassays, including rocket
      immunoelectrophoresis, enzyme immunoassay, and immunoblotting. The present study
      demonstrates that the sensitivity of the described biosensor technique is
      comparable to the most sensitive enzymed-linked immunosorbent assays.

PMID- 16792087
TI  - Biosensor screening for veterinary drug residues in foodstuffs.
AB  - The advent of the surface plasmon resonance (SPR) biosensor has led to many
      applications in diverse fields from the pharmaceutical industry to the life
      sciences and other areas within biotechnology. One area that has seen a
      significant increase in applications is the testing for veterinary drug residues
      in foodstuffs. These include tests for antibiotics, beta-agonists, and
      antiparasitic drugs. The introduction of the Biacore Q in the late 1990s, an SPR
      biosensor dedicated to the food industry, and the complementary development of
      kits to test for these residues mean that end users have a viable alternative
      screening test to the established enzyme-linked immunosorbent assay (ELISA)
      techniques. This paper reviews many SPR biosensor veterinary drug tests that have
      been developed, with particular emphasis placed on kit-based assays.

PMID- 16792088
TI  - Immunobiosensor detection of domoic acid as a screening test in bivalve molluscs:
      comparison with liquid chromatography-based analysis.
AB  - A rapid and sensitive immuno-based screening method was developed to detect
      domoic acid (DA) present in extracts of shellfish species using a surface plasmon
      resonance-based optical biosensor. A rabbit polyclonal antibody raised against DA
      was mixed with standard or sample extracts and allowed to interact with DA
      immobilized onto a sensor chip surface. The characterization of the antibody
      strongly suggested high cross-reactivity with DA and important isomers of the
      toxin. The binding of this antibody to the sensor chip surface was inhibited in
      the presence of DA in either standard solutions or sample extracts. The DA chip
      surface proved to be highly stable, achieving approximately 800 analyses per chip
      without any loss of surface activity. A single analytical cycle (sample
      injection, chip regeneration, and system wash) took 10 min to complete. Sample
      analysis (scallops, mussels, cockles, oysters) was achieved by simple extraction
      with methanol. These extracts were then filtered and diluted before analysis.
      Detection limits in the ng/g range were achieved by the assay; however, the assay
      parameters chosen allowed the test to be performed most accurately at the
      European Union's official action limit for DA of 20 microg/g. At this
      concentration, intra- and interassay variations were measured for a range of
      shellfish species and ranged from 4.5 to 7.4% and 2.3 to 9.7%, respectively.

PMID- 16792089
TI  - Biosensors for the analysis of food- and waterborne pathogens and their toxins.
AB  - Biosensors are devices which combine a biochemical recognition element with a
      physical transducer. There are various types of biosensors, including
      electrochemical, acoustical, and optical sensors. Biosensors are used for medical
      applications and for environmental testing. Although biosensors are not commonly
      used for food microbial analysis, they have great potential for the detection of
      microbial pathogens and their toxins in food. They enable fast or real-time
      detection, portability, and multipathogen detection for both field and laboratory
      analysis. Several applications have been developed for microbial analysis of food
      pathogens, including E. coli O157:H7, Staphylococcus aureus, Salmonella, and
      Listeria monocytogenes, as well as various microbial toxins such as
      staphylococcal enterotoxins and mycotoxins. Biosensors have several potential
      advantages over other methods of analysis, including sensitivity in the range of
      ng/mL for microbial toxins and <100 colony-forming units/mL for bacteria. Fast or
      real-time detection can provide almost immediate interactive information about
      the sample tested, enabling users to take corrective measures before consumption
      or further contamination can occur. Miniaturization of biosensors enables
      biosensor integration into various food production equipment and machinery.
      Potential uses of biosensors for food microbiology include online process
      microbial monitoring to provide real-time information in food production and
      analysis of microbial pathogens and their toxins in finished food. Biosensors can
      also be integrated into Hazard Analysis and Critical Control Point programs,
      enabling critical microbial analysis of the entire food manufacturing process. In
      this review, the main biosensor approaches, technologies, instrumentation, and
      applications for food microbial analysis are described.

PMID- 16792090
TI  - Rapid analysis of coumarins using surface plasmon resonance.
AB  - Coumarin molecules are ubiquitous in nature. Several have come to prominence as
      potential clinical therapeutic candidates. The principal example is warfarin,
      which is a very widely prescribed anticoagulant. Other coumarin derivatives, such
      as aflatoxin B1, are insidious contaminants in crop-derived foodstuffs. Extreme
      potency is a common feature of all biochemically active coumarins and, thus
      reliable methods for their rapid and sensitive detection are of paramount
      importance. Accordingly, this review examines the current methods used in the
      analysis of these molecules and compares them with immunoassay-based strategies.
      As a case study, we report on our experiences with using coumarin-specific
      polyclonal, monoclonal, and recombinant antibodies in conjunction with a surface
      plasmon resonance-based biosensor for analysis of coumarins. We chart the assay
      development process and demonstrate high sensitivity and reproducibility that
      compares favorably with established methodologies.

PMID- 16792091
TI  - Surface plasmon resonance for detection of genetically modified organisms in the
      food supply.
AB  - A review is presented demonstrating that biospecific interaction analysis, using
      surface plasmon resonance (SPR) and biosensor technologies is a simple, rapid,
      and automatable approach to detect genetically modified organisms (GMOs). Using
      SPR, we were able to monitor in real-time the hybridization between
      oligonucleotide or polymerase chain reaction (PCR)-generated probes and target
      single-stranded PCR products obtained by using as substrates DNA isolated from
      normal or transgenic soybean and maize. This procedure allows a one-step,
      nonradioactive detection of GMOs. PCR-generated probes are far more efficient in
      detecting GMOs than are oligodeoxyribonucleotide probes. This is expected to be a
      very important parameter, because information on low percentage of GMOs is of
      great value. Determination of the ability of SPR-based analysis to quantify GMOs
      should be considered a major research field for future studies, especially for
      the analyses of food supplies.

PMID- 16792092
TI  - Determination of minor proteins of bovine milk and colostrum by optical biosensor
      analysis.
AB  - Automated, rapid, sensitive, and label-free biosensor-based immunoassays for
      immunoglobulin G (IgG), folate binding protein, lactoferrin, and lactoperoxidase
      in bovine milk using surface plasmon resonance optical detection with direct
      binding assay format are described. Samples are prepared for analysis by direct
      dilution into buffer. Analysis conditions, including ligand immobilization, flow
      rate, contact time, and regeneration are defined and nonspecific binding
      considerations evaluated. The technique has been applied to the measurement of
      these proteins in consumer milks, colostrum, milk products, and infant formulas,
      and their temporal change during early bovine lactation followed.

PMID- 16792093
TI  - A generative sketch model for human hair analysis and synthesis.
AB  - In this paper, we present a generative sketch model for human hair analysis and
      synthesis. We treat hair images as 2D piecewise smooth vector (flow) fields and,
      thus, our representation is view-based in contrast to the physically-based 3D
      hair models in graphics. The generative model has three levels. The bottom level
      is the high-frequency band of the hair image. The middle level is a piecewise
      smooth vector field for the hair orientation, gradient strength, and growth
      directions. The top level is an attribute sketch graph for representing the
      discontinuities in the vector field. A sketch graph typically has a number of
      sketch curves which are divided into 11 types of directed primitives. Each
      primitive is a small window (say 5 x 7 pixels) where the orientations and growth
      directions are defined in parametric forms, for example, hair boundaries,
      occluding lines between hair strands, dividing lines on top of the hair, etc. In
      addition to the three level representation, we model the shading effects, i.e.,
      the low-frequency band of the hair image, by a linear superposition of some
      Gaussian image bases and we encode the hair color by a color map. The inference
      algorithm is divided into two stages: 1) We compute the undirected orientation
      field and sketch graph from an input image and 2) we compute the hair growth
      direction forthe sketch curves and the orientation field using a Swendsen-Wang
      cut algorithm. Both steps maximize a joint Bayesian posterior probability. The
      generative model provides a straightforward way for synthesizing realistic hair
      images and stylistic drawings (rendering) from a sketch graph and a few Gaussian
      bases. The latter can be either inferred from a real hair image or input (edited)
      manually using a simple sketching interface. We test our algorithm on a large
      data set of hair images with diverse hair styles. Analysis, synthesis, and
      rendering results are reported in the experiments.

PMID- 16792094
TI  - Minimum classification error training for online handwriting recognition.
AB  - This paper describes an application of the Minimum Classification Error (MCE)
      criterion to the problem of recognizing online unconstrained-style characters and
      words. We describe an HMM-based, character and word-level MCE training aimed at
      minimizing the character or word error rate while enabling flexibility in writing
      style through the use of multiple allographs per character. Experiments on a
      writer-independent character recognition task covering alpha-numerical characters
      and keyboard symbols show that the MCE criterion achieves more than 30 percent
      character error rate reduction compared to the baseline Maximum Likelihood-based
      system. Word recognition results, on vocabularies of 5k to 10k, show that MCE
      training achieves around 17 percent word error rate reduction when compared to
      the baseline Maximum Likelihood system.

PMID- 16792095
TI  - Recovering 3D human body configurations using shape contexts.
AB  - The problem we consider in this paper is to take a single two-dimensional image
      containing a human figure, locate the joint positions, and use these to estimate
      the body configuration and pose in three-dimensional space. The basic approach is
      to store a number of exemplar 2D views of the human body in a variety of
      different configurations and viewpoints with respect to the camera. On each of
      these stored views, the locations of the body joints (left elbow, right knee,
      etc.) are manually marked and labeled for future use. The input image is then
      matched to each stored view, using the technique of shape context matching in
      conjunction with a kinematic chain-based deformation model. Assuming that there
      is a stored view sufficiently similar in configuration and pose, the
      correspondence process will succeed. The locations of the body joints are then
      transferred from the exemplar view to the test shape. Given the 2D joint
      locations, the 3D body configuration and pose are then estimated using an
      existing algorithm. We can apply this technique to video by treating each frame
      independently--tracking just becomes repeated recognition. We present results on
      a variety of data sets.

PMID- 16792096
TI  - A locally constrained watershed transform.
AB  - The watershed transform, from mathematical morphology, is a powerful and flexible
      tool for segmentation. However, it does not allow a priori knowledge relating to
      characteristics of region boundaries to be included in the way that other
      approaches do. This paper introduces the locally constrained watershed transform,
      which includes border constraints by modifying the underlying path definition
      upon which the watershed transform depends. This approach maintains many of the
      desirable properties of the watershed transform, such as well-defined stopping
      conditions and efficient implementation, while offering more stable segmentation
      in the presence of noisy or incomplete boundaries.

PMID- 16792097
TI  - Edge-preserving image denoising and estimation of discontinuous surfaces.
AB  - In this paper, we are interested in the problem of estimating a discontinuous
      surface from noisy data. A novel procedure for this problem is proposed based on
      local linear kernel smoothing, in which local neighborhoods are adapted to the
      local smoothness of the surface measured by the observed data. The procedure can
      therefore remove noise correctly in continuity regions of the surface and
      preserve discontinuities at the same time. Since an image can be regarded as a
      surface of the image intensity function and such a surface has discontinuities at
      the outlines of objects, this procedure can be applied directly to image
      denoising. Numerical studies show that it works well in applications, compared to
      some existing procedures.

PMID- 16792098
TI  - Asymmetric bagging and random subspace for support vector machines-based
      relevance feedback in image retrieval.
AB  - Relevance feedback schemes based on support vector machines (SVM) have been
      widely used in content-based image retrieval (CBIR). However, the performance of
      SVM-based relevance feedback is often poor when the number of labeled positive
      feedback samples is small. This is mainly due to three reasons: 1) an SVM
      classifier is unstable on a small-sized training set, 2) SVM's optimal hyperplane
      may be biased when the positive feedback samples are much less than the negative
      feedback samples, and 3) overfitting happens because the number of feature
      dimensions is much higher than the size of the training set. In this paper, we
      develop a mechanism to overcome these problems. To address the first two
      problems, we propose an asymmetric bagging-based SVM (AB-SVM). For the third
      problem, we combine the random subspace method and SVM for relevance feedback,
      which is named random subspace SVM (RS-SVM). Finally, by integrating AB-SVM and
      RS-SVM, an asymmetric bagging and random subspace SVM (ABRS-SVM) is built to
      solve these three problems and further improve the relevance feedback
      performance.

PMID- 16792099
TI  - Learning weighted metrics to minimize nearest-neighbor classification error.
AB  - In order to optimize the accuracy of the Nearest-Neighbor classification rule, a
      weighted distance is proposed, along with algorithms to automatically learn the
      corresponding weights. These weights may be specific for each class and feature,
      for each individual prototype, or for both. The learning algorithms are derived
      by (approximately) minimizing the Leaving-One-Out classification error of the
      given training set. The proposed approach is assessed through a series of
      experiments with UCI/STATLOG corpora, as well as with a more specific task of
      text classification which entails very sparse data representation and huge
      dimensionality. In all these experiments, the proposed approach shows a uniformly
      good behavior, with results comparable to or better than state-of-the-art results
      published with the same data so far.

PMID- 16792100
TI  - Rapid object indexing using locality sensitive hashing and joint 3D-signature
      space estimation.
AB  - We propose a new method for rapid 3D object indexing that combines feature-based
      methods with coarse alignment-based matching techniques. Our approach achieves a
      sublinear complexity on the number of models, maintaining at the same time a high
      degree of performance for real 3D sensed data that is acquired in largely
      uncontrolled settings. The key component of our method is to first index surface
      descriptors computed at salient locations from the scene into the whole model
      database using the Locality Sensitive Hashing (LSH), a probabilistic approximate
      nearest neighbor method. Progressively complex geometric constraints are
      subsequently enforced to further prune the initial candidates and eliminate false
      correspondences due to inaccuracies in the surface descriptors and the errors of
      the LSH algorithm. The indexed models are selected based on the MAP rule using
      posterior probability of the models estimated in the joint 3D-signature space.
      Experiments with real 3D data employing a large database of vehicles, most of
      them very similar in shape, containing 1,000,000 features from more than 365
      models demonstrate a high degree of performance in the presence of occlusion and
      obscuration, unmodeled vehicle interiors and part articulations, with an average
      processing time between 50 and 100 seconds per query.

PMID- 16792101
TI  - A systolic algorithm for Euclidean distance transform.
AB  - The Euclidean distance transform is one of the fundamental operations in image
      processing. It has been widely used in computer vision, pattern recognition,
      morphological filtering, and robotics. This paper proposes a systolic algorithm
      that computes the Euclidean distance map of an N x N binary image in 3N clocks on
      2N(2) processing cells. The algorithm is designed so that the hardware resources
      are reduced; especially no mulitipliers are used and, thus, it facilitates VLSI
      implementation.

PMID- 16792102
TI  - Structure from motion with wide circular field of view cameras.
AB  - This paper presents a method for fully automatic and robust estimation of two
      view geometry, autocalibration, and 3D metric reconstruction from point
      correspondences in images taken by cameras with wide circular field of view. We
      focus on cameras which have more than 180 degrees field of view and for which the
      standard perspective camera model is not sufficient, e.g., the cameras equipped
      with circular fish-eye lenses Nikon FC-E8 (183 degrees), Sigma 8mm-f4-EX (180
      degrees), or with curved conical mirrors. We assume a circular field of view and
      axially symmetric image projection to autocalibrate the cameras. Many wide field
      of view cameras can still be modeled by the central projection followed by a
      nonlinear image mapping. Examples are the above-mentioned fish-eye lenses and
      properly assembled catadioptric cameras with conical mirrors. We show that
      epipolar geometry of these cameras can be estimated from a small number of
      correspondences by solving a polynomial eigenvalue problem. This allows the use
      of efficient RANSAC robust estimation to find the image projection model, the
      epipolar geometry, and the selection of true point correspondences from tentative
      correspondences contaminated by mismatches. Real catadioptric cameras are often
      slightly noncentral. We show that the proposed autocalibration with approximate
      central models is usually good enough to get correct point correspondences which
      can be used with accurate noncentral models in a bundle adjustment to obtain
      accurate 3D scene reconstruction. Noncentral camera models are dealt with and
      results are shown for catadioptric cameras with parabolic and spherical mirrors.

PMID- 16792103
TI  - Full-frame video stabilization with motion inpainting.
AB  - Video stabilization is an important video enhancement technology which aims at
      removing annoying shaky motion from videos. We propose a practical and robust
      approach of video stabilization that produces full-frame stabilized videos with
      good visual quality. While most previous methods end up with producing smaller
      size stabilized videos, our completion method can produce full-frame videos by
      naturally filling in missing image parts by locally aligning image data of
      neighboring frames. To achieve this, motion inpainting is proposed to enforce
      spatial and temporal consistency of the completion in both static and dynamic
      image areas. In addition, image quality in the stabilized video is enhanced with
      a new practical deblurring algorithm. Instead of estimating point spread
      functions, our method transfers and interpolates sharper image pixels of
      neighboring frames to increase the sharpness of the frame. The proposed video
      completion and deblurring methods enabled us to develop a complete video
      stabilizer which can naturally keep the original image quality in the stabilized
      videos. The effectiveness of our method is confirmed by extensive experiments
      over a wide variety of videos.

PMID- 16792104
TI  - Detection and analysis of hair.
AB  - We develop computational models for measuring hair appearance for comparing
      different people. The models and methods developed have applications to person
      recognition and image indexing. An automatic hair detection algorithm is
      described and results reported. A multidimensional representation of hair
      appearance is presented and computational algorithms are described. Results on a
      data set of 524 subjects are reported. Identification of people using hair
      attributes is compared to eigenface-based recognition along with a joint,
      eigenface-hair-based identification.

PMID- 16792105
TI  - Rotation recovery from spherical images without correspondences.
AB  - This paper addresses the problem of rotation estimation directly from images
      defined on the sphere and without correspondence. The method is particularly
      useful for the alignment of large rotations and has potential impact on 3D shape
      alignment. The foundation of the method lies in the fact that the spherical
      harmonic coefficients undergo a unitary mapping when the original image is
      rotated. The correlation between two images is a function of rotations and we
      show that it has an SO(3)-Fourier transform equal to the pointwise product of
      spherical harmonic coefficients of the original images. The resolution of the
      rotation space depends on the bandwidth we choose for the harmonic expansion and
      the rotation estimate is found through a direct search in this 3D discretized
      space. A refinement of the rotation estimate can be obtained from the
      conservation of harmonic coefficients in the rotational shift theorem. A novel
      decoupling of the shift theorem with respect to the Euler angles is presented and
      exploited in an iterative scheme to refine the initial rotation estimates.
      Experiments show the suitability of the method for large rotations and the
      dependence of the method on bandwidth and the choice of the spherical harmonic
      coefficients.

PMID- 16792106
TI  - Motion and shape recovery based on iterative stabilization for modest deviation
      from planar motion.
AB  - We describe an iterative stabilization method that can simultaneously recover
      camera motion and 3D shape from an image sequence captured under modest deviation
      from planar motion. This technique iteratively applies a factorization method
      based on planar motion and can approximate the observed image points to the 2D
      points projected under planar motion by stabilizing the camera motion. We apply
      the proposed method to aerial images acquired by a helicopter-borne camera and
      show better reconstruction of both motion and shape than Christy-Horaud's
      perspective factorization. Moreover, we confirm that the reprojection errors
      calculated from the recovered camera motion and 3D shape are very similar to the
      optimum results yielded by bundle adjustment.

PMID- 16792108
TI  - Delivery system helps clinicians produce more accurate master impressions.

PMID- 16792107
TI  - Addressing the shortage of dentists in underserved areas.

PMID- 16792109
TI  - Oral cancer detection system is simple to use and noninvasive.

PMID- 16792110
TI  - Studies vindicate amalgam as health threat.

PMID- 16792111
TI  - Keys to capturing the returning patient.

PMID- 16792113
TI  - Implications of bisphosphonate use for the dentist: an introduction.

PMID- 16792112
TI  - Teaching the use of liners, bases, and cements: a 10-year follow-up survey of
      North American Dental Schools.

PMID- 16792114
TI  - General cosmetic dentistry photographs for communicating and consulting with your
      technician.

PMID- 16792115
TI  - Virtual diagnostics using cone bean CT.

PMID- 16792116
TI  - Managing variables in radiographic imaging for implant dentistry.

PMID- 16792117
TI  - Rules of engagement: mastering the endodontic game, Part 1.

PMID- 16792118
TI  - Adopting a new philosophy: minimal invasion.
AB  - Dentistry is a dynamic profession with new trends evolving. Minimally invasive
      dentistry is becoming not just a concept but a way of practicing. Creative people
      are finding ways, materials, and technology that enable patients to experience
      less hard-tissue or soft-tissue removal, improved prevention and maintenance, and
      increased attention to a philosophy of "less is more." The World Congress of
      Minimally Invasive Dentistry was formed to facilitate the sharing of these new
      concepts. The members embrace change, and dentistry offers the constant
      opportunity for such. As the standard of care moves toward minimally invasive
      dentistry, patients will benefit.

PMID- 16792119
TI  - The many uses of cosmetic imaging.

PMID- 16792120
TI  - Management of periodontitis for HIV-AIDS patients: case study.

PMID- 16792121
TI  - Live longer, live better: lifestyle diseases and their prevention, Part 1.

PMID- 16792122
TI  - The number one practice mistake and how to avoid it.

PMID- 16792123
TI  - Filling in the blanks for practice management software.

PMID- 16792124
TI  - Government launches media offensive amid pound 500m deficit.

PMID- 16792125
TI  - Politicians in line for a drubbing.

PMID- 16792126
TI  - Comms failure hampered London bombing response.

PMID- 16792127
TI  - Private finance initiative. Trusts feel the impact as PFI and payment by results
      collide.

PMID- 16792128
TI  - Goodbye and hello.

PMID- 16792129
TI  - So you want to be a director?

PMID- 16792130
TI  - Barometer. Acute trusts May 2006.

PMID- 16792131
TI  - Friends and relations.
AB  - Good political relationships can bring tangible rewards, as well as helping to
      protect your reputation. There will be shared goals and joint working will
      deliver more health improvements to more groups of people. Build communication
      with the media and politicians--and meet key people regularly to maintain it.

PMID- 16792132
TI  - Roles of TGF-beta1 and apoptosis in the progression of glomerulosclerosis in
      human IgA nephropathy.
AB  - Apoptotic glomerular cells have been detected in the severely damaged glomeruli
      that are a consequence of human IgA nephropathy. Transforming growth factor-(TGF)
      beta1 is known to induce apoptosis in cultured mesangial cells. To clarify
      whether TGF-beta1 contributes to the progression of IgA nephropathy by activating
      apoptosis in glomerular cells, we examined the expression of TGF-beta1 gene and
      apoptotic changes in kidney biopsy samples, and assessed those relations to the
      severity of nephropathy. 32 patients with IgA nephropathy, showing proteinuria (>
      1 g/day) and serum creatinine less than 1.5 mg/dl were classified according to
      glomerular sclerosis index (GSI) into 3 groups (Group I: GSI < 0.3,Group 11: 0.3
      < or = GSI < 1.0, Group: III GSI > or = 1.0). Computer-aided morphometry of
      glomeruli and arteries, and terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling of fragmented DNA (TUNEL) staining were performed. Expression
      of TGF-beta1 and caspase-3 mRNAs in renal biopsy samples was analyzed by real
      time PCR (Taq Man method). Increased glomerular area, interstitial fibrosis,
      lymphocytic infiltration, and tubulointerstitial changes were observed to
      accompany increased severity of GSI. TUNEL index was higher in Group III. The
      levels of TGF-beta1 and caspase-3 mRNAs were significantly increased in Group III
      (183 and 190%, respectively). Furthermore, caspase-3 mRNA levels were tightly
      associated with TGF-beta1 mRNA expression (r = 0.677, p < 0.0001). The present
      study suggests that the activation of TGF-beta1 plays a role in the progression
      of IgA nephropathy even in the moderate degree of glomerular injury, in part via
      activation of apoptosis of glomerular cells.

PMID- 16792133
TI  - Tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome.
AB  - BACKGROUND: Steroid resistance and steroid dependence constitute a major problem
      in the treatment of minimal-change disease and focal segmental glomerulosclerosis
      (FSGS). Cyclophosphamide and cyclosporine are well-established alternative
      immunomodulating agents, whereas data on FK 506 (tacrolimus) are rare. METHODS:
      The present work provides data from 10 patients of an open, monocentric, non
      randomized, prospective trial. Five patients with steroid-dependent minimal
      change nephrotic syndrome, 1 patient with steroid-refractory minimal-change
      disease and 4 patients with steroid-refractory FSGS were started on tacrolimus at
      trough levels of 5 10 microg/l. In case of steroid-dependence, prednisolone was
      tapered off in presence oftacrolimus within one month. RESULTS: Within 6 months,
      complete remission was achieved in 5 patients (50%) and partial remission in 4
      patients (40%), yielding a final response rate of 90%. One patient was primarily
      resistent to tacrolimus (steroid-refractory minimal-change), another patient
      became secondarily resistant to tacrolimus after an initial remission (steroid
      refractory FSGS). Average proteinuria significantly decreased by 77% from 9.5 +/-
      1.4 - 2.2 +/- 1.1 g/day (p < 0.01). Serum protein significantly raised from 55.0
      +/- 1.9 - 64.6 +/- 1.9 g/l (p < 0.01). Tacrolimus induced non-significant
      increases of blood glucose (4.9 +/- 0.1 - 5.1 +/- 0.2 mmol/l), systolic blood
      pressure (131.4 +/- 7.1 - 139.0 +/- 7.6 mmHg) and creatinine (93.2 +/- 13.9 103.2
      +/- 15.3 mmol/l). Five patients have been tapered off tacrolimus so far,
      nephrotic syndrome relapsed in 4 of them (80%). Relapse occurred at tacrolimus
      levels between 2.6 and 6.9 ng/ml. CONCLUSIONS: Our data suggest that tacrolimus
      may be a promising alternative to cyclosporine both in steroid-resistant and
      steroid-dependent nephrotic syndrome.

PMID- 16792134
TI  - Excess risk of renal allograft loss and early mortality among elderly recipients
      is associated with poor exercise capacity.
AB  - BACKGROUND: Successful renal transplantation in the elderly offers substantial
      benefits in quality and life expectancy. However, in this group of patients there
      is an early increased risk of death compared with those remaining on dialysis.
      MATERIALS AND METHODS: Graft and patient outcomes in 64 older transplant
      recipients were compared with 338 patients aged 18 - 59 years. We identified
      potential risk factors that may predict clinical outcomes in older transplant
      recipients. A log-rank test and Cox regression analyses were performed to assess
      the impact of various patient characteristics on graft and patient survival.
      RESULTS: Among older patients, graft survival was 76.6% and 67% at 1 and 3 years,
      respectively. When graft survival was censored for death with functioning graft,
      the 1- and 3-year graft survival was 83% and 82%, respectively. Patient survival
      was 78% and 71% at 1 and 3 years, respectively. These survival rates were
      significantly lower than those of younger recipients. Pretransplant inactivity,
      delayed graft function, smoking history and longer waiting time predicted poor
      graft and patient survival. A history of chronic obstructive pulmonary disease,
      and peripheral vascular disease also predicted a higher mortality among older
      recipients. CONCLUSION: Older kidney transplant recipients are at high risk for
      allograft failure and early death. Poor functional capacity predicts a poor
      outcome for older patients undergoing renal transplantation. Therefore, careful
      patient selection is paramount, and every effort should be made to initiate
      timely interventions aimed at increasing physical activity in those with low
      fitness level.

PMID- 16792135
TI  - Prevalence of weight gain in patients with better renal transplant function.
AB  - AIMS: This study investigates the association between renal function and change
      in weight after kidney transplantation. METHODS: Retrospective analyses of 165
      transplant patients on maintenance steroids who were followed-up for 6.2 +/- 2.4
      years. RESULTS: 101 males and 64 females participated in the study. Results are
      expressed as mean +/- SD. At the first post-transplant outpatient visit (time 0),
      BMI was 25.3 +/- 4.8 kg/m2. It increased significantly by 7.7 +/- 10.8% and 10.9
      +/- 12.6% at 1 and 5 years. 18 and 29% of patients had a BMI > 30 kg/m2 at times
      0 and 5 years, respectively. Thereafter, diminishing glomerular filtration rate
      (GFR) was associated with the loss of the excess weight. Multivariate analysis
      showed that GFR, but not age, race, sex, source of graft, number of HLA
      mismatches or length of dialysis was significant to post-transplant weight gain.
      38 patients gained weight > 1 SD above the mean of the population and were
      designated the high weight gain (HWG) group. 41 patients gained weight < the mean
      - 1 SD of the population and were designated the low weight gain (LWG) group. GFR
      in the high and low weight gain groups at time 0 was 71.8 +/- 20.3 ml/min/1.73 m2
      and 66.4 +/- 23.1 ml/min/1.73 m2, respectively (p = NS), as compared to 77.4 +/-
      23.3 ml/min/1.73 m2 and 61.5 +/- 24.5 ml/min/ 1.73 m2 at 6 months, respectively
      (p < 0.01) and continued to be significant thereafter (72.7 +/- 17.2 ml/min/1.73
      m2 and 58.9 +/- 19.8 ml/min/1.73 m2, p < 0.05 at 6 years). CONCLUSIONS: Patients
      with relatively better renal transplant function gained more weight, suggesting a
      pivotal role of improved appetite on weight gain post transplantation. Most of
      the weight gain occurred during the first year.

PMID- 16792136
TI  - A randomized trial of intermittent versus continuous oral alfacalcidol treatment
      of hyperparathyroidism in end-stage renal disease.
AB  - BACKGROUND: Secondary hyperparathyroidism, a major clinical problem in patients
      with chronic renal failure, develops in response to phosphate retention and
      impaired calcitriol [1,25-dihydroxyvitamin D3] synthesis. Vitamin D therapy,
      particularly alfacalcidol [1 alpha-hydroxyvitamin D3], has been shown to be
      effective in the treatment of secondary hyperparathyroidism. The aim of this
      study was to compare the effect of a 12-week course of continuous versus
      intermittent oral alfacalcidol therapy on parathyroid hormone suppression.
      PATIENTS AND METHODS: 34 patients were selected and randomly divided into 2
      groups to receive either intermittent or continuous oral alfacalcidol. Baseline
      data were obtained on serum calcium, phosphorus, alkaline phosphatase and PTH.
      All but the PTH were monitored monthly. PTH levels were measured again until the
      end of the protocol. The intervention was 2 microg of alfacalcidol given after
      each dialysis session (intermittent group) or 1 microg given 6 days/week
      (continuous group). RESULTS: Serum calcium and phosphorus showed a tendency to
      increase from baseline levels in both groups. Mean PTH levels for both groups
      showed a progressive reduction over time during the study period. This decrement
      showed no significant difference with regard to the schedule of alfacalcidol
      administration when comparing the 2 groups. There also was no difference in the
      incidence of side effects--hypercalcemia and hyperphosphatemia--between the
      intermittent and continuous intervention. CONCLUSION: Feedback regulation of PTH
      with oral alfacalcidol therapy is efficient in the treatment of
      hyperparathyroidism. However, intermittent and continuous oral administration are
      equally effective in suppressing an elevated PTH level in hemodialysis patients,
      with similar safety margins.

PMID- 16792137
TI  - Antibiotic lock technique reduces the incidence of temporary catheter-related
      infections.
AB  - BACKGROUND: In the hemodialytic population, infections are the second leading
      cause of death; access infections account for a large proportion of this
      mortality. The antibiotic lock technique has been applied to infected tunneled
      catheters as rescue or prophylaxis medication to reduce infection rates. In
      addition, application of topical antibiotic ointments to tunneled and non
      tunneled catheters also prevents exit site infections. METHODS: 17 patients with
      25 catheters participated in our study from March 2004 - February 2005. The
      catheter lock comprised of mixed cefazolin (5 mg/dl) with heparin (2,500 IU/ml)
      and mupirocin was topically applied to the area (2 x 2 cm) surrounding the
      catheter exit site. RESULTS: The catheter infection rate was reduced from 12.7
      times/1,000 catheter days to 5.02 times/1,000 catheter days in patients with
      jugular vein catheters. The total catheter-related infection rate was 14.9
      times/1,000 catheter days in the control group and 4.1 times/1,000 catheter days
      in the study group. The reduction in catheter infections was more evident in a
      subgroup of non-diabetic patients, and in those with femoral catheters.
      CONCLUSION: The use of antibiotic lock and topical antibiotics significantly
      reduces the incidence of temporary catheter-related infections, especially in non
      diabetic patients and in those with femoral catheters.

PMID- 16792138
TI  - Complete remission of minimal-change nephrotic syndrome induced by apheresis
      monotherapy.
AB  - We report a case of a 17-year-old male with relapse of minimal-change nephrotic
      syndrome (MCNS), in whom apheresis monotherapy without steroids or
      immunosuppressants resulted in complete remission. The patient initially
      developed nephrotic syndrome in February 1998. The first renal biopsy confirmed
      the diagnosis of MCNS. The patient was also found to be a carrier of hepatitis B
      virus. Steroid therapy was started with oral prednisolone 60 mg/day. Complete
      remission was achieved in 3 months, and the steroid treatment was tapered off in
      May 2001. During the steroid tapering, temporal exacerbation of liver function
      was noted. In July 2002, the patient was admitted to our hospital again due to
      relapse of nephrotic syndrome. Second biopsy reconfirmed the diagnosis of MCNS.
      Since the serum titer of HBV was elevated, apheresis monotherapy was selected to
      avoid the risk of steroid-induced fulminant hepatitis. Four sessions of low
      density lipoprotein apheresis (LDL-A) and 5 sessions of double-filtration
      plasmapheresis (DFPP) reduced the proteinuria from 9.2 g/day to 0.2 g/day over 38
      days without any additional medication. Proteinuria remained suppressed below 0.2
      g/day for more than 12 months and no exacerbation of liver function was observed
      up to the final follow-up in September 2003. The present case suggested the
      potential of apheresis monotherapy to induce and maintain complete remission of
      MCNS and an important role of circulating factors in the pathogenesis of MCNS.

PMID- 16792139
TI  - Fanconi's syndrome and distal (type 1) renal tubular acidosis in a patient with
      primary Sjogren's syndrome with monoclonal gammopathy of undetermined
      significance.
AB  - Tubulointerstitial nephritis is a well-recognized complication in primary
      Sjogrens syndrome. Fanconi's syndrome is a far less frequent complication
      compared with distal tubular dysfunction. We here describe a 49-year-old woman
      with primary Sjogren's syndrome. In 1997, she was diagnosed with primary
      Sjogren's syndrome with tubulointerstitial nephritis, and was then treated with
      oral prednisolone for the tubulointerstitial nephritis. In 2002, she was referred
      to our hospital because of progressive fatigue. At that time, biclonal spike on
      serum protein (IgG-kappa and IgA-kappa) and Bence-Jones protein in urine were
      found. Bone marrow aspiration showed 1.0% plasma cell infiltration. Thus, a
      diagnosis of monoclonal gammopathy of undetermined significance (MGUS) was made.
      In 2004, she was again admitted to our hospital because of mild renal dysfunction
      and hypokalemia. Laboratory evaluation showed inappropriate, alkaline urine in
      hyperchloremic metabolic acidosis and a positive urine anion gap, indicating the
      presence of distal (Type 1) renal tubular acidosis (RTA). The urine concentration
      defect was also found. Further studies revealed proximal tubular dysfunction,
      including renal glycosuria, generalized aminoaciduria, phosphaturia, uricosuria
      and proximal RTA. The kidney biopsy represented diffuse and severe
      tubulointerstitial nephritis with dense infiltrates of lymphocytes and IgA and K
      light chain-positive plasma cells. No findings of multiple myeloma or malignant
      lymphoma were observed. In conclusion, our patient had Sjogren's syndrome with
      MGUS and exhibited dysfunction of both proximal tubule (Fanconi's syndrome) and
      distal tubule, which may be attributed to diffuse tubulointerstitial nephritis.

PMID- 16792140
TI  - Successful outpatient treatment of renal vein thrombosis by low-molecular weight
      heparins in 3 patients with nephrotic syndrome.
AB  - Renal vein thrombosis (RV Thromb) is a serious complication ofnephrotic syndrome.
      Anticoagulation is usually recommended as the treatment of choice. This study
      reports 3 nephrotic patients diagnosed to have RVThromb combined with
      thromboembolic events. Low-molecular weight heparin (LMWHep) was given
      subcutaneously every 12 hours following the diagnosis of RVTromb, which continued
      at the outpatient clinic after an average of 11 in-hospital days. The patients
      visited the nephrology outpatient clinic every other week and underwent magnetic
      resonance image (MRI) studies at 6-week intervals for follow-up of patency of the
      involved renal vein. LMWHep was discontinued when MRI showed this patency. The
      average outpatient treatment period was 74 days. There was no recurrent RVThromb
      in the follow-up course of 6 months after discontinuation of LMWHep. Kidney
      function was preserved, as indicated by image studies and serial renal function
      tests. LMWHep produced a more predictable anti-coagulant effect, a superior
      bioavailability, a longer half-life and a dose-independent effect than
      unfractionated heparin and coumadin. These benefits made the outpatient treatment
      of RVThromb possible. Our report recommends outpatient treatment of RVThromb by
      LMWHep because it is feasible, effective and safe.

PMID- 16792141
TI  - Low-grade T-cell lymphoma of the kidney and Waldenstrom's macroglobulinemia in a
      patient presenting with renal failure.
AB  - Renal failure is rarely the presenting manifestation of non-Hodgkin's lymphoma.
      We describe the unusual case of a patient who presented with uremia due to
      lymphomatous infiltration of the kidney by a low-grade T-cell lymphoma. The
      diagnosis of lymphoma was made by renal biopsy. Extrarenal nodular or extra
      nodular involvement could not be detected. However, simultaneously, a
      lymphoplasmacytic lymphoma was found on bone marrow biopsy associated with IgM
      paraproteinemia. To our knowledge, this is the first report of a renal T-cell
      lymphoma associated with Waldenstrom's macroglobulinemia.

PMID- 16792142
TI  - Life-threatening hemorrhage from abdominal aorta following a percutaneous renal
      biopsy.
AB  - We report on a case of life-threatening abdominal aorta hemorrhage following
      percutaneous renal biopsy. A 42-year-old woman with chronic kidney disease stage
      2 and microscopic hematuria underwent a percutaneous renal biopsy to evaluate
      renal insufficiency. One hour following the biopsy procedure, she complained of
      an abdominal pain and developed signs ofoligemic shock. In despite of 4 blood
      units transfusion, the patient continued to be in shock. She was transmitted
      urgently to the operating room without any other examinations (such as abdominal
      computer tomography) and underwent an emergency laparotomy. A transverse tear in
      the abdominal aorta was identified as the bleeding site, and after occlusion, the
      hemorrhage was stopped. The patient gradually recovered and she was discharged in
      good clinical condition after a few days.

PMID- 16792143
TI  - Sarcoidosis-related hypercalcemia in 3 chronic hemodialysis patients.
AB  - Hypercalcemia is a frequent complication in chronic hemodialysis (CHD) patients.
      A rare cause of this condition is sarcoidosis, and has only been reported 6 times
      in CHD. Herein, we report on 3 cases of sarcoidosis-related hypercalcemia in CHD
      patients: an overt case, a probable case, and a recurrence of pre-dialysis
      sarcoidosis. Hypercalcemia is a frequent complication in chronic hemodialysis
      patients: it is often related to uncontrollable secondary hyperparathyroidism or
      to the inappropriate use of calcium phosphate binders, 1alpha-hydroxylated
      vitamin D metabolites, high dialysate calcium concentrations, or to aluminium
      related bone disease [Uach and Bover 1996]. However, other rare causes should
      also be considered, such as multiple myeloma, non-Hodgkin lymphoma [Uach and
      Bover 1996], vitamin A intoxication [Fishbane et al. 1995], or granulomatous
      diseases such as sarcoidosis. The latter has only been described in a total of 6
      hemodialysis patient reports [Barbour et al. 1981, Barnard et al. 2002, Herrero
      et al. 1998, Kalantar-Zadeh et al. 1994, Kuwae et al. 2003, Naito et al. 1999].
      In the present paper, we report on 3 cases of sarcoidosis-related hypercalcemia
      in chronic hemodialysis patients with 3 different patterns, i.e. overt
      sarcoidosis, probable sarcoidosis, and recurrence of pre-dialysis sarcoidosis.

PMID- 16792144
TI  - Recurring enteric peritonitis associated with non-perforating colon carcinoma.
AB  - Peritonitis of enteric origin may occur during treatment with peritoneal dialysis
      due to visceral perforation or injury or, in the absence of perforation, due to
      transmural migration of enteric bacteria across the bowel wall into the
      peritoneal cavity. To the best of our knowledge, peritonitis has not previously
      been reported associated with carcinomatous colon polyp in the absence of bowel
      wall perforation. We describe the case of a 31-year-old female who experienced
      recurring episodes of enteric peritonitis associated with a clinically occult
      adenocarcinoma of the colon, without having any other known risk factors for
      peritonitis. A 15 mm carcinomatous polyp was not visible on CT scan but was found
      at colonoscopy with polypectomy. She proceeded to transverse colectomy; the
      resected colon showed no evidence of bowel wall perforation. This case
      demonstrates that a non-perforating carcinomatous polyp of the colon may
      predispose to enteric peritonitis in the setting of peritoneal dialysis, and it
      emphasizes the importance of making an aggressive search for underlying
      pathology, in patients who present with recurring enteric peritonitis or unusual
      presentations of enteric peritonitis.

PMID- 16792146
TI  - Crush syndrome after multiple dog bites.

PMID- 16792145
TI  - Bacterial meningitis--complication from a dialysis catheter.
AB  - Various infective complications associated with dialysis catheter infection have
      been reported in the literature previously. We report a case of a hemodialysis
      patient presented with confusion and dysarthria secondary to Staphylococcus
      aureus septicemia and meningitis originating from a tunneled catheter used for
      providing dialysis. Blood cultures from the periphery, central venous catheter
      and culture of the line tip grew methicillin-sensitive Staphylococcus aureus.
      Lumbar puncture after CT brain confirmed Staphylococcus aureus. He was treated
      with high dose of an appropriate parenteral antibiotic and also removal of the
      infected line. In spite of optimal treatment, he died 15 days following his
      admission. The ideal option will be to use a definitive access like a fistula or
      AV graft, but in practice a significant proportion of hemodialysis patients is
      dialyzed with temporary or tunneled catheters all over the world, and infection
      poses a serious threat to dialysis patients resulting in significant mortality
      and morbidity. In patients with dialysis catheter-related sepsis, removal of the
      infected catheters and appropriate antibiotic treatment will prevent serious
      metastatic complications. Planning definitive access well ahead in chronic kidney
      disease patients and minimizing the use of temporary access is the only way
      forward.

PMID- 16792147
TI  - Prednisone/cyclophosphamide treatment in adult-onset autosomal dominant familial
      focal segmental glomerulosclerosis (FSGS 1).

PMID- 16792148
TI  - [Pharmacological and clinical evalutation of nasal obstruction: application to
      xylometazoline].
AB  - Nasal obstruction, a prominent feature of rhinitis, may be quantified in humans
      by haemodynamic techniques (measuring local blood flux), static methods
      (measuring the geometry of nasal cavities) and dynamic methods (assessing the
      patency of nasal airways through the measure of resistance to air flow). These
      methods demonstrated the nasal decongestant activity of xylometazoline in healthy
      volunteers and rhinitis patients. Controlled double-blind studies established the
      clinical efficacy of xylometazoline in infectious and allergic (seasonal and
      perennial) rhinitis versus placebo and in comparison with various reference
      substances. The effects on nasal epithelium ciliary activity which are observed
      in vitro are modest and even less pronounced in vivo owing to dilution in situ
      and protective physiological processes.

PMID- 16792149
TI  - [The French National Medicines Assessment Committee, innovation and therapeutic
      progress].
AB  - In France the role of the French National Medicines Assessment Committee, which
      is a part of the French National Authority for Health (HAS), is to evaluate the
      expected performance of new drugs in comparison with that of existing drug or non
      drug treatments. This process includes evaluation of degree of innovation
      generally based on whether the drug can be considered as possibly, likely or
      certain to represent a factor of progress. However innovation and progress are
      not always synonymous. Progress is defined in terms of improvement in efficacy or
      tolerance determined by estimating the impact of the new product in comparison
      with existing modalities on the health of a subgroup of patients that can be
      readily defined, identified and studied. In general the committee considers any
      originality as positive since a new chemical or pharmacological class or a new
      mechanism of action may allow treatment of patients that did not respond to or
      tolerate existing products. However, when confronted with a concept without clear
      clinical benefits, the committee must distinguish between true and false
      innovation so that deliberation focuses more on recognition and quantification of
      progress than on systematic evaluation of innovation.

PMID- 16792150
TI  - [Pharmacoepidemiology of psychotropic medication: utilisation and impact in real
      life conditions].
AB  - Pharmacoepidemiological studies exploring utilisation of psychotropic medications
      in real-life conditions are required to identify extension of indications, since
      the risk of gap between the theoretical target population and the population
      actually treated is especially marked for this class of drugs. A large proportion
      of subjects from the general population are exposed to psychotropic medications,
      so even a small increase in the risk of adverse effect may have major deleterious
      consequences for the health of the general population. Hence,
      pharmacoepidemiological studies are also required to explore the risk/benefit
      ratio of these drugs in real-life conditions. These studies may provide answers
      to currently unsolved public health questions, such as the long-term cognitive
      impact of exposure to benzodiazepines, the impact of antidepressant on suicidal
      behaviour, or the risks associated with enlarged use of antipsychotics. Only
      findings obtained by such studies may allow risk management and elaboration of
      guidelines based upon factual data.

PMID- 16792151
TI  - [Are the prescriptions of anticholinesterasic drugs adapted to the associated
      diseases and/or drugs in the Alzheimer's dementia?].
AB  - The aim of this study was to evaluate if the prescriptions of anticholinesterase
      drugs took into account some diseases and drugs which could interfere with them,
      in 58 inpatients (82 years old). The anticholinesterase drugs were respectively
      at admission and discharge: donepezil (n = 27 and 34), galantamine (n = 12 and
      19) and rivastigmine (n = 3 and 1). Nineteen patients received a combination of
      anticholinesterase drug with an anticholinergic drug (muscarinic antipsychotic 15
      times). Twelve patients had a medical history which interfered with the
      anticholinesterase drug: uretroprostatic obstacle, chronic renal failure and
      auriculo-ventricular block. Thirty-five adverse drug reactions, mainly in
      digestive track, were recorded in 26 patients. The treatment with
      anticholinesterase drug was modified only in 18 patients and the combination of
      anticholinesterase drug and antipsychotic agent was stopped in 5 patients. In
      conclusion, inappropriated prescriptions of anticholinesterase drugs seem
      frequent, with a more important prevalence of adverse drug reactions than in
      prospective studies. These results incite to develop studies of evaluation of
      prescriptions of anticholinesterase drugs.

PMID- 16792152
TI  - [Drugs, Parkinson's disease and parkinsonian syndroms: recent advances in
      pharmacovigilance].
AB  - This paper reviews recent data on the pharmacovigilance of antiparkinsonian drugs
      and drugs inducing parkinsonian syndroms. Sudden sleep attacks were first
      described in 1999 with dopamine agonists. In fact, they can be induced by all the
      dopaminergic antiparkinsonian drugs. Favorising factors are duration of the
      disease, dose of dopaminergic drugs, daytime somnolence or dysautonomia. This
      adverse drug reaction can be serious leading, for example, to road accidents.
      Cardiac valvulopathies were more recently (end of 2002) described with pergolide.
      Thus, this dopamine agonist should now be prescribed as a last choice among
      dopamine agonists. Dopamine drugs (levodopa as well as dopamine agonists) can
      induce hypersexual behaviours or pathological gambling. Among the long list of
      drugs inducing parkinsonian syndroms, recent data suggest the involvement of
      serotoninergic antidepressants, valproic acid and trimetazidine. Finally, these
      data on pharmacovigilance allow to precise the physiological role of dopamine:
      beside its motor and psychic effects, dopamine is also involved in the sleep
      arousal control. It is also an important mediator for pleasure, hedonic
      regulations and sexual behaviour. This review also underlines the major role of
      spontaneous reports to the pharmacovigilance systems to identify new adverse drug
      reactions.

PMID- 16792153
TI  - [A review of potential signals generated by an automated method on 3324
      pharmacovigilance case reports].
AB  - Automated signal generation aims to focus the attention of pharmacovigilance
      experts on drug-ADR associations which are disproportionally present in a
      spontaneous reporting system. Since 1986, we could find several signals using
      classic pharmacovigilance techniques with case reports registered in our
      pharmacovigilance regional centre. From this dataset 3,324 cases were related to
      spontaneous reporting. Drug-ADR associations were generated by using a Data
      Mining Algorithm (DMA) proposed by Evans et al. Potential signals were evaluated
      by reviewing case reports related to the unlabelled associations. The DMA
      generated 523 associations of which 107 were not described in the SPC. Most
      potential signals were false positives. Although the DMA generated little
      additional knowledge compared to signals already detected using classic
      techniques, the whole process helped us to focus our case review on a very small
      subset of the whole dataset (9.6%).

PMID- 16792154
TI  - [Misuse of clonazepam (Rivotril): recent trends].
AB  - Recent observations suggest the existence of clonazepam abuse. In order to
      determine the importance of this practice and the characteristics of these
      consumers, a study has been carried out, based on data from the Provence-Alpes
      Cote-d'Azur and Corsica health reimbursement system. Individuals from these
      regions affiliated to the French health reimbursement system, who have had a
      prescription of clonazepam reimbursed between January 1, 2001 and February 15,
      2001, have been selected. The deliveries have been monitored over a 9 month
      period. 9381 subjects have been selected. A sub-group of 1.5 per cent subjects
      with a deviant behaviour has been identified by factorial analysis and has been
      compared to the sub-group without deviant behaviour. The subjects with deviant
      behaviour are younger and mostly male. The dosage of clonazepam is higher (10.8
      mg per day versus 2.1 mg per day) with a significantly higher proportion of
      benzodiazepine and high-dose buprenorphine. The number of deliveries is higher
      (19.4 versus 5.9) as well as the number of different physicians (4.5 versus 1.5)
      and pharmacies (5.9 versus 1.3). This study provides some arguments in favor of
      the potential of abuse and dependence of clonazepam and the necessity to
      reinforce its monitoring. This information requires to be relayed to health
      professionals.

PMID- 16792155
TI  - [A case of interstitial lung disease with atorvastatin (Tahor) and a review of
      the literature about these effects observed under statins].
AB  - The 3-Hydroxy-3-methyl-glutaryl coenzyme A (HGM-CoA) reductase inhibitors, or
      statins, are competitive inhibitors of the rate-limiting enzyme in cholesterol
      synthesis. Generally, statins have an excellent safety profile. Elevations of
      liver transaminases and creatine phosphokinase with myalgia have been associated
      with the use of HGM-Co A reductase inhibitors, case reports of rhabdomyolysis are
      rare, most occurring with concomitant use with other drugs such as cyclosporin,
      fusidic acid and gemfibrozil. We describe here the clinical case of a patient who
      developed interstitial lung disease as probably a result of the use of statins
      which particularly increased with long-term atorvastatin treatment. The present
      review details some case-reports of interstitial lung disease reported under
      statins in the literature. Few systemic adverse effects such as lupus-like
      syndromes and polymyositis have been reported. Recent experimentations have
      demonstrated that cholesterol is not the only intracellular target of statins but
      that they also have a potential role in atherosclerosis and in organ
      transplantation as immunosuppressor agents.

PMID- 16792156
TI  - [Utilization patterns of creams indicated in burns].

PMID- 16792157
TI  - [Selective serotonin reuptake inhibitors and acne].

PMID- 16792158
TI  - [Fluoroquinolones-induced tendinitis: shoulder is not under shelter].

PMID- 16792159
TI  - [Fluidione-acetaminophen interaction: A case report].

PMID- 16792161
TI  - Nightmares induced by valsartan.

PMID- 16792160
TI  - [Symptomatic high chromogranin A level associated with rabeprazole and
      ranitidine].

PMID- 16792162
TI  - [Treatment of diabetic hyperosmolar coma and references during the initial
      medical training].

PMID- 16792163
TI  - [Evaluate and improve the comprehension of the information in biomedical
      research].

PMID- 16792164
TI  - [Homage to Professor Michel Breteau].

PMID- 16792165
TI  - Surgical outcomes in chronic rhinosinusitis and nasal polyposis.

PMID- 16792166
TI  - Olfaction in rhinology--methods of assessing the sense of smell.
AB  - Olfactory disorders frequently occur in rhinological disease. Different
      subjective and objective test methods are available to assess the sense of
      olfaction. Among the subjective methods, screening tests and threshold
      measurements are commonly used to quantify hyposmia or anosmia. Qualitative
      methods are available using discrimination and identification tests. Objective
      methods are used in research and in some medicolegal situations. Objective tests
      include olfactory evoked potentials, functional Magnetic Resonance Imaging and
      functional Positron Emission Tomography. The measurement of the sense of smell
      helps to assess the whole spectrum of the effects of nasal disease. This is
      especially important before rhinological surgery, because a non-detected smell
      disorder in patients with rhinological disease is common. The assessment of a pre
      existing hyposmia or anosmia helps to avoid a postoperative claim that this was
      caused by surgery. A variety of validated screening tests for olfaction is
      available and they are a useful tool to document whether a patient is able to
      smell.

PMID- 16792167
TI  - The 'best method' of topical nasal drug delivery: comparison of seven techniques.
AB  - OBJECTIVE: To determine whether there is a 'best' technique for delivering drugs
      to the middle meatus. DESIGN: Single-blind cross-over study in healthy
      individuals using endoscopic video-imaging. PARTICIPANTS: A dyed test formulation
      was administered intranasally on seven non-sequential days to ten healthy
      individuals with no 'nasal' history. The participants were recruited through
      advertisement. MAIN OUTCOME MEASURES: Comparison of seven different techniques,
      20 nostrils and 140 endoscopic videos for the deposition patterns of dyed test
      formulation. Analysis was possible in 90% of all endoscopic videos. Three head
      positions were tested for both nasal drops and nasal sprays. RESULTS: Deposition
      of dyed test formulation near the middle meatus was observed in 43% of all
      observations. No significant differences were observed in terms of delivery
      between any of the seven techniques. CONCLUSIONS: Our study suggests there may
      not be a single 'best' technique for topical nasal drug delivery. A more
      individual approach to topical nasal drug treatment, taking anatomy and head
      position into account would seem to be more appropriate.

PMID- 16792168
TI  - The endoscopic Draf II frontal sinusotomy: non-navigated approach.
AB  - OBJECTIVE: Endoscopic endonasal Draf II frontal sinusotomy is indicated for a
      variety of pathologies such as mucocele and non-responsive chronic frontal
      sinusitis. However, this approach is challenged and controversial. The objectives
      were to evaluate the advantages, disadvantages, indications, and rate of
      complications of this approach, without the use of a navigation system. METHODS:
      The files and computed tomography (CT) scans of 25 patients who underwent
      endoscopic endonasal Draf II sinusotomy at Assaf Harofeh Medical Center between
      1999 and 2002 were reviewed. RESULTS: Thirty-one frontal sinuses were operated on
      and follow-up was between 18 and 62 months (average 30.3). Twenty-two sinuses
      (71%) had previous surgery. The Draf II procedure was used in 3.7% of all cases
      during the survey period. The most frequent indication for surgery was
      inflammation (48%) followed by mucocele (28%). In all but 2 sinuses (93%), the
      frontal floor between the lamina papyracea and the middle concha was drilled out.
      Twenty-four patients (96%) were successfully ventilated. No major complications
      were noted. CONCLUSIONS: The Draf II approach can be used safely and successfully
      without a navigation system, including cases of revision endoscopic sinus
      surgery. Correct interpretation of the surgical field and a CT scan are crucial
      for success. Careful patient selection is essential for this procedure.

PMID- 16792169
TI  - Functional rhinoplasty with batten and spreader grafts for correction of internal
      nasal valve incompetence.
AB  - OBJECTIVE: We a describe technique for correction of internal nasal valve
      incompetence (INVI) using functional rhinoplasty (FRP) with combined
      cartilaginous batten and spreader grafts and report the functional and cosmetic
      outcomes. DESIGN: Prospective series using subjective improvement in nasal airway
      and quality of life. SETTING: Subregional ENT centre, one operating rhinologist.
      PARTICIPANTS: Twenty-three consecutive adults presenting to ENT department at
      North Hertfordshire NHS Trust with symptomatic INVI. MAIN OUTCOMES MEASURES: Pre
      and post-operative symptom scores for nasal obstruction and its impact on overall
      quality of life using visual analogue scales (1-100mm). Cosmetic outcome graded
      using subjective scores. Statistical analysis performed using the Wilcoxon signed
      rank test. RESULTS: We found a median subjective improvement on the visual
      analogue scale of 55 mm for nasal patency (p<0.001) and of 49 mm for quality of
      life (p<0.001). Twenty-two patients felt that the appearance of their nose had
      not changed or had significantly improved post operatively. CONCLUSION: Combined
      use of batten and spreader grafts for the correction of INVI in normal or narrow
      nasal vaults is effective without compromising cosmesis.

PMID- 16792170
TI  - Sub-alar batten grafts as treatment for nasal valve incompetence; description of
      technique and functional evaluation.
AB  - OBJECTIVE: To describe and evaluate the functional results of a surgical
      technique for treating nasal valve incompetence, in which a cartilage graft
      called a sub-alar batten graft is placed along the undersurface of the lateral
      crus of the lower lateral cartilage. METHODS: The functional outcomes of 27
      patients who had sub-alar batten grafts placed on 39 sides were evaluated by
      means of clinical examination and subjective self-assessment. RESULTS: Of a total
      of 39 sides operated upon, 10 (26%) were rated as optimal, 15 (39%) as improved,
      13 (33%) as equal and 1 (2%) as worse. Overall on 25 sides (65%) the post
      operative situation was considered to be better than pre-operatively. In all
      cases in which there was a wish for cosmetic improvement, besides the functional
      indication, this was obtained, and in no case did the grafts give cause to
      cosmetic grievances or other complications. CONCLUSION: Placement of sub-alar
      battens had a positive effect on nasal valve function in roughly two thirds of
      cases in this series. Although in our opinion this result was slightly
      disappointing from a purely functional point of view, they can improve the
      cosmetic result and continue to be considered in cases in which avoidance of
      surface irregularities is a primary concern or as a preventative measure in
      rhinoplasty patients at risk for post-operative valve collapse.

PMID- 16792171
TI  - Long term effects of cutting forceps in endoscopic sinus surgery.
AB  - BACKGROUND: At present, some authors prefer cutting forceps to conventional non
      cutting forceps in Endoscopic Sinus Surgery, based on the assumption of superior
      wound healing due to mucosal preservation, without any proof of better clinical
      outcome. The purpose of this study was to elaborate our previously reported short
      term results, by evaluating the long-term outcome. METHODS: One hundred
      consecutive patients, who underwent a bilateral Endoscopic Sinus Surgery
      procedure, received follow-up in a prospective, double-blinded way. Cutting
      forceps had been randomly used on one side and non-cutting forceps on the other
      side. Lateralised symptoms (headache, maxillary pressure, nasal obstruction and
      secretions) and endoscopic findings (secretion, pus, blood, crusts, oedema,
      polyps and adhesions) were evaluated on both sides 1 year postoperatively.
      RESULTS: Both types of instruments gave satisfactory healing situations. Similar
      to the short-term follow-up results, no significant difference in the global
      symptom and endoscopic score between the 2 types of instruments was found. The
      analysis of individual symptoms and endoscopic parameters also showed no
      difference. CONCLUSION: Cutting forceps do not result in a better subjective or
      endoscopic healing evaluation after one year, compared to non-cutting forceps.

PMID- 16792172
TI  - Expression and localization of TRPV1 in human nasal mucosa.
AB  - Capsaicin is the pungent principle in chili peppers and previous studies reported
      that topical application of capsaicin to patients with allergic and non-allergic
      rhinitis produced significant and long-lasting relief of symptoms. The capsaicin
      receptor (TRPV1, VR1) is a nociceptive transducer and the existence of TRPV1 in
      non-neuronal cells as well as neuronal cells has been reported. In order to
      clarify the role of TRPV1 on the upper airway, we examined the localization and
      the expression of TRPV1 in human nasal mucosa. Surgically obtained human nasal
      specimens were processed for immunohistochemistry with commercial anti-TRPV1
      antibody. We also performed immunofluorescence with anti-TRPV1 antibody and anti
      neurofilament antibody or anti-CD31 antibody. Epithelial cells and vascular
      endothelial cells were cultured from nasal turbinates, respectively. For RT-PCR
      analysis, total RNA was isolated, and then RT-PCR was performed.
      Immunohistochemical studies revealed that TRPV1 positive cells were found on
      epithelial cells, vascular endothelial cells, submucosal glands and nerves in
      human nasal mucosa. By RT-PCR analysis, the mRNA expression of TRPV1 was
      confirmed in human nasal mucosa. These results suggest that capsaicin can
      directly influence the epithelial secretory and various functions via TRPV1 as
      well as the activation of the sensory neurons.

PMID- 16792173
TI  - Post-infectious olfactory dysfunction exhibits a seasonal pattern.
AB  - HYPOTHESIS: We investigated whether olfactory dysfunction following infections of
      the upper respiratory tract (post-URTI) has an incidence matching the seasonality
      of URTIs. STUDY DESIGN: Retrospective study. METHODS: In total, 457 patients (126
      male, 331 female) with post-URTI olfactory loss were examined during a 6-year
      period (1999-2004). Their records were assessed for age, sex, and time of onset
      of the disease. The severity of olfactory dysfunction was assessed using the
      "Sniffin' Sticks" (odour threshold, odour discrimination, and odour
      identification). RESULTS: Incidence of post-URTI olfactory dysfunction exhibited
      seasonal fluctuations with deviations from the winter seasonality of URTIs. The
      overall incidence of the disease differed significantly between months. March
      (12.7%) and May (12.6%) were the months with the highest incidence of the disease
      throughout the year. The lowest incidence was observed in September (5.6%).
      Significant differences were found between these months and months with a high
      incidence of URTIs. DISCUSSION: The peak incidence of post-URTI olfactory loss in
      March may be explained by the high incidence of influenza at this time. However,
      it is unclear why the incidence of the disease presents a second peak in May,
      when the incidence of respiratory viruses is relatively low. Climate conditions
      at this time might play a role in the susceptibility of the nasal epithelia
      towards certain viral infections, e.g. parainfluenza type III. CONCLUSION: Post
      URTI olfactory dysfunction exhibits spring seasonality with peaks in March and
      May and possible causative factors being influenza and parainfluenza viruses
      (type III), respectively.

PMID- 16792174
TI  - Nasal RANTES and eotaxin production pattern in response to rhinovirus infection.
AB  - Tissue eosinophilia is a hallmark of nasal polyposis and its pathogenesis is an
      area of high interest. RANTES and eotaxin are both known to recruit eosinophils,
      however, the mechanisms triggering their induction are still uncertain, and viral
      infections have been suggested to be involved in this process. Therefore, we
      investigated whether rhinovirus infection is a stimulus for RANTES and eotaxin
      expression and production. Fibroblasts were cultured from healthy nasal mucosa
      obtained during endonasal surgery. Cultured cells were infected with human
      rhinovirus-16 for one to 72 hours. Following total RNA isolation and reverse
      transcription, RANTES- and eotaxin-mRNA levels were analyzed. In addition, RANTES
      and eotaxin secretion was measured in culture supernatants by means of an ELISA.
      Rhinovirus infection induces RANTES-mRNA expression as early as one hour after
      infection, persisting for up to 72 hours. Eotaxin-mRNA profiles did not alter
      significantly from control. Protein production was confirmatory for both
      chemokines, indicating distinct translational latency. Our data suggest that
      RANTES functions as a host defence mechanism responding to rhinovirus infection,
      thus supporting a linkage between rhinovirus infections and the pathogenesis of
      nasal polyposis.

PMID- 16792175
TI  - Eosinophilic nasal polyps are a rich source of eotaxin, eotaxin-2 and eotaxin-3.
AB  - INTRODUCTION: The CC-chemokine eotaxin plays a key role in the pathologic
      mechanism of tissue eosinophilia in nasal polyposis. In this study, we
      investigated a possible role of eotaxin-2 and eotaxin-3, the recently discovered
      members of the eotaxin family. METHODS: Nasal polyps from 24 patients (non
      allergic/allergic/aspirin-intolerant patients) and turbinate tissue from 8
      controls were investigated. Chemokine protein content (eotaxin, eotaxin-2, and 
      3) of tissue homogenates was measured by ELISA. Paraffin sections of samples were
      stained to determine the extent of eosinophilia. RESULTS: Protein expression of
      eotaxin, eotaxin-2 and eotaxin-3 was significantly higher in nasal polyps than in
      controls. There was a direct correlation between the protein concentrations of
      all three eotaxins. Further, protein levels of all chemokines were significantly
      correlated to the amount of eosinophilia. In aspirin-sensitive polyps the number
      of eosinophils was significantly higher than in the other patient groups and they
      had significantly higher eotaxin, eotaxin-2, and -3 protein levels than non
      allergic and significantly higher amounts of eotaxin-3 compared with allergic
      patients. CONCLUSIONS: Our findings suggest, that all members of the eotaxin
      family are involved in the pathogenesis of nasal polyposis. The results are more
      likely indicative of a complex cooperation between all members of the eotaxin
      family than of a specific role in the development of eosinophilia and nasal
      polyposis.

PMID- 16792176
TI  - Epistaxis and its management: an observational pilot study carried out in 23
      hospital centres in France.
AB  - OBJECTIVE: The purpose of this study is to describe the treatment of epistaxis in
      hospital emergency departments and to identify the principal risk factors for
      more severe episodes of bleeding. STUDY PROTOCOL: Prospective cross-sectional
      epidemiological study MATERIAL AND METHODS: This study was carried out in 23
      hospital centres in France, most of them teaching hospitals. Every patient
      presenting non-traumatic epistaxis or else associated with hereditary hemangioma
      during two consecutive and separate 24-hour periods were included. RESULTS: Fifty
      patients were included in the study. Nasal bleeding was stopped within 30 minutes
      for 47 patients. Fourteen patients were hospitalized. The risk factors for severe
      epistaxis included either copious bleeding or else bleeding for more than 6 hours
      or patients aged 65 and over. A history of repeated nasal packing and/or taking
      medication with a known hemorrhagic risk was associated with the amount and
      duration of bleeding (p < 0.05). CONCLUSION: Risk factors for severe epistaxis
      should be identified as to improve patient care and avoid treatment failure or
      useless hospitalization.

PMID- 16792177
TI  - Characterization of nasal paraffinoma following septorhinoplasty by attenuated
      total reflection--fourier transform infrared spectroscopy (ATR-FTIR).
AB  - Vaseline and paraffin have been injected into various parts of the body.
      Vaselinoma and paraffinoma are well-described complications, despite which nasal
      packing with Vaseline gauze is still common in the management of epistaxis, after
      rhinoplasty, endonasal surgery, to control bleeding and prevent synechiae or
      restenosis. Our aim is to highlight this complication, propose a safe method for
      its diagnosis and establish guidelines for its prevention. We report two cases of
      paraffinoma occurring after rhinoplasty and discuss prevention of this rare but
      serious complication, and suggest an alternative dressing. Attenuated total
      reflection (ATR) FI7R spectra have proven to be a definitive characterising tool
      for surgical extracts, guaranteeing detection of mineral products that histology
      does not offer. For these lesions we propose the name "petroleum oilomas" which
      we feel to be more appropriate than the more commonly used paraffinomas.
      Relevance of the work: a description of an innovative and safe method of
      diagnosis, and proposal of a procedure for postrhinoplasty packing (without
      mineral oils) to avoid this complication.

PMID- 16792178
TI  - Acoustic rhinometry in small children.
AB  - OBJECTIVES: To study how acoustic rhinometry succeeds in a sample of small
      children of one to six years of age and to evaluate reasons for failed
      recordings. METHODS: Twenty-six healthy children one to six years of age were
      invited to the Helsinki University Hospital, Department of Otorhinolaryngology
      for clinical examination and measurements with acoustic rhinometry. RESULTS:
      Three children of ten refused recordings in the age group of one to two years.
      The children's nose adaptor was too small for three of seven children in the age
      group of three to four years. The anatomical nose adaptor and the adult nose tube
      were suitable for children between five to six years of age. CONCLUSIONS:
      Acoustic rhinometry is well tolerated and usually well accepted in small
      children. The recordings succeeded in most children. However, lack of adequate
      equipment hinders measurements in part of the children.

PMID- 16792179
TI  - Inverted papilloma of the sphenoid sinus: presentation of three cases.
AB  - INTRODUCTION: Inverted papilloma deriving originally from the sphenoid sinus is
      extremely rare. Three such cases are presented aiming to show the particularities
      and diagnostic clues of this clinical entity. CASE REPORTS: All three patients
      were male, and presented mainly with nasal symptoms. In all three cases imaging
      shows the sphenoid sinus was completely occupied by the tumor. Additionally the
      ethmoids and nasal cavities have been invaded in contiguity to the site of the
      initial appearance of the tumor. In particular one of the cases was of even more
      interest as a malignant transformation of the inverted papilloma of the sphenoid
      sinus was histologically observed. Endoscopic sinus surgery was the therapeutic
      approach chosen for all three cases, with very good results. Follow up 30 months
      after the operation has not revealed any signs of recurrence of the disease.
      CONCLUSION: Inverted papilloma of the sphenoid sinuses--and even more malignant
      transformation--although quite rare, may present occasionally. The ENT surgeon
      should be aware of this condition. Preoperative imaging with CT scan and MRI and
      the experience of the surgeon will dictate the appropriate surgical approach.

PMID- 16792180
TI  - Early depictions of the human anterior nasal septum.
AB  - In the literature, remarks on the depiction of the anterior nasal septum in
      prehistoric times cannot be found. Studying works of art from some archaeological
      sites of Asia, Asia Minor, Near East, Egypt, and Southeastern Europe the
      anatomical depiction of the columella and the nostrils in human figures are
      shown. These figures or heads, partly appearing as masks, were made of ivory,
      stone, marble, terracotta, steatite, reeds and clay, or of burned limestone.
      Faces and figures sculpted in the time between the Upper Palaeolithic (30,000 -
      25,000 BC) and the Early Bronze Age (3,300 - 2,400 BC) are presented as examples
      of our ancestors' outstanding skill to create works of art with an astonishing
      ability to observe anatomical details. The tendency to create a human nose in a
      natural manner can already be recognized in the figurines of the Upper
      Palaeolithic.

PMID- 16792181
TI  - [Towards a united continuing nursing education program].

PMID- 16792182
TI  - [Developing a united system for accreditation. Developing quality nursing
      education--consequences for the timely structure of continuing education in
      Germany].

PMID- 16792183
TI  - [The Bologna interpretation and tuning project. The next step for nurses].

PMID- 16792184
TI  - [International Council of Nurses in a fight against tuberculosis].

PMID- 16792186
TI  - [ALIDA development of senior centers: a sign of recovery].

PMID- 16792185
TI  - [Help in the logistics of work].

PMID- 16792187
TI  - [No exit: escape pathways in dangerous fire accidents].

PMID- 16792188
TI  - [In the colors of the art of people with dementia].

PMID- 16792189
TI  - [Meeting of delegates 2006].

PMID- 16792190
TI  - [Timely defence proposal: home visits from visiting nurses are helpful].

PMID- 16792191
TI  - [Leadership must be recognized].

PMID- 16792192
TI  - [Courtesy on the job pays off in every case].

PMID- 16792193
TI  - [The personal model].

PMID- 16792194
TI  - [Action plan for stroke prevention].

PMID- 16792195
TI  - [Insulin analogues--which dimension should be discussed?].

PMID- 16792196
TI  - [Neurokinin 1 receptor antagonists--between hope and disappointment].
AB  - Substance P (SP)/Neurokinin 1 (NK1) receptor pathways have been repeatedly
      implicated in the pathophysiology of central, pulmonary, and gastric disorders. A
      large body of evidence that has been generated from animal experiments indicates
      that treatment with selective NK1 receptor antagonists might be effective in the
      treatment of certain forms of disorders, analgesia, depression, migraine, asthma,
      or gastrointestinal disorders. Accordingly, numerous NK1 receptor antagonists
      have either been synthesized and are under clinical development, or have already
      been tested in clinical trials. However, the initial encouraging clinical results
      were followed by repeated demonstration of a lack of effectiveness. Up to now,
      only one NK1 receptor antagonist, aprepitant, is available for therapeutical use.
      Aprepitant is a selective high-affinity human SP/NK1 receptor antagonist approved
      by the FDA in 2003. Aprepitant is indicated for prophylaxis of acute- and delayed
      phase nausea and emesis caused by chemotherapy regimens. It is used in
      combination with a 5-hydroxytryptamine (5-HT3) antagonist and a corticosteroid.
      It is the first antiemetic agent that acts by binding the NK1 receptor. Research
      continues and novel molecules may show better pharmacokinetic and pharmacodynamic
      properties and, therefore, may achieve therapeutic success.

PMID- 16792197
TI  - [Pertussis--not only a childhood disease].
AB  - Whouping cough (pertussis) is a highly contagious respiratory illness of humans
      that is caused predominantly by the gram-negative bacterial pathogen Bordetella
      pertussis. The disease shows a variety of symptoms, dependent on the patients'
      age and immunity. During the last years, the pertussis incidence has increased in
      several parts of the world. There has been a shift in the epidemiology of
      disease, with more cases reported in older age groups, specifically adolescents
      and adults. Macrolides are regarded to be the treatment of choice for the
      management of B. pertussis infections. Active immunization with whole cell and in
      particular acellular vaccines is the mainstay for prevention of disease.

PMID- 16792198
TI  - [Lung cancer--epidemiology, prognosis and therapy].
AB  - Lung cancer is one of the most common cancer diagnoses, sadly with a bad
      prognosis. The main risk factor is smoking. There are two major types of lung
      cancer: non-small cell lung cancer und small cell lung cancer. The difference is
      important for prognosis and therapy. The prognosis for patients with small-cell
      lung cancer is worse; the treatment is based on chemotherapy. In patients with
      non-small cell lung cancer surgery and radiotherapy are more important.

PMID- 16792199
TI  - [Pharmacotherapy of a patient with Alzheimer's disease: interactions with the
      antidementive galantamine].
AB  - Based on a case-report, drug-related problems of the therapy of a female patient
      with Alzheimer's disease are discussed. According to the SOAP scheme options for
      optimizing the pharmacotherapy are discussed.

PMID- 16792200
TI  - [Protection form the sun. A frequent question in the pharmacy].

PMID- 16792201
TI  - [Heart disease prevention diet. Which is the best?].

PMID- 16792202
TI  - [Hyperhomocysteinemia as a risk factor for vascular diseases].

PMID- 16792203
TI  - [Effective reductions of LDL cholesterol levels with dual antilipemics].

PMID- 16792204
TI  - [Lower coronary risk with aggressive cholesterol inhibition?].

PMID- 16792205
TI  - [Combination of drug therapy and changing life-style on weight loss success].

PMID- 16792206
TI  - [Risk of thrombosis following long flights].

PMID- 16792207
TI  - [Obesity and diseases of the alimentary canal].

PMID- 16792209
TI  - [Prosthesis implantation with bone cement].

PMID- 16792208
TI  - [Transdermal rotigotine as monotherapy for Parkinson disease].

PMID- 16792211
TI  - Consumed by guilt, I just stopped eating. First anorexic, then bulimic, I always
      found new ways to punish myself. Finally, I'm whole again.

PMID- 16792210
TI  - [Diabetes mellitus. Is the direction of injection practices unclear?].

PMID- 16792212
TI  - The magic of the family meal.

PMID- 16792213
TI  - Rethinking first foods.

PMID- 16792214
TI  - Is Teflon risky? Nonstick pots can emit nasty stuff if used incorrectly.

PMID- 16792215
TI  - Decoding the grocery store.

PMID- 16792216
TI  - Does my diet fit my genes? The new science of nutrigenomics has some answers. It
      explains why fat and caffeine are worse for some than others.

PMID- 16792217
TI  - 2 thin chefs. Want to learn the secrets of willpower? Just ask a couple of
      slender women who spend their days surrounded by temptation.

PMID- 16792218
TI  - The grass-fed revolution. Beef raised wholly on pasture, rather than grain-fed in
      feedlots, may be better for your health--and for the planet.

PMID- 16792219
TI  - How sweet it isn't. If artificial sugar is so splendid, why aren't we thin?

PMID- 16792220
TI  - Retooling school lunch. How two communities are working to serve kids fresher,
      healthier food--and then actually get them to eat it.

PMID- 16792221
TI  - The menu magician. Gregg Rapp knows just how to influence what you order.

PMID- 16792222
TI  - Catering to the melting pot.

PMID- 16792223
TI  - Six rules for eating wisely.

PMID- 16792224
TI  - How to curb your cravings.

PMID- 16792225
TI  - CEO IT Achievement Award. Putting it all together. Leaving behind big-city
      living, Glenn Steele Jr. makes IT dreams a reality at small-town system.

PMID- 16792226
TI  - Connecting patients, docs. Site offers medical data, physician access and more.

PMID- 16792227
TI  - Charitable intentions. CHA, VHA unveil community-benefit guidelines developed to
      help not-for-profit hospitals justify their tax exemptions.
AB  - With new guidelines from the CHA and VHA on reporting community benefits, not-for
      profit hospitals are being advised to drop bad debt and Medicare shortfalls from
      their accounting of how they fulfill their mission. While the AHA doesn't agree,
      some experts do. MedPAC member Nancy Kane, right, says bad debt "is a tough one,
      but I don't think a lot of bad debt is a community benefit.

PMID- 16792228
TI  - O'Leary's legacy. Exiting JCAHO president revamped surveys.

PMID- 16792229
TI  - CMS gets online transparency. Payments to docs, hospitals will be shown by
      county.

PMID- 16792230
TI  - Healthways gets bigger.

PMID- 16792231
TI  - Hospital stays of uninsured stable: AHRQ.

PMID- 16792232
TI  - Overlapping interests? Conflict questions arise at regional IT groups.

PMID- 16792233
TI  - Stop playing politics with charity. CHA's new community benefits measure merely a
      step in right direction.

PMID- 16792234
TI  - Workforce Report 2006. 'Beginning to see what a nurse is'. With baby boomers
      ready to pass the torch, ever-younger nurses learn the difference between
      schoolwork and real work.

PMID- 16792235
TI  - The hazy doc shortage. There's a serious problem, but lack of clarity forestalls
      solutions.

PMID- 16792236
TI  - Workforce Report 2006. The healthcare workforce 2006--at a glance.

PMID- 16792237
TI  - Time's not on their side-yet. Researchers hope to optimize nurses' efficiency.

PMID- 16792238
TI  - By the numbers. Health systems with highest number of full-time employees.

PMID- 16792239
TI  - Gain-sharing seems to be working, but......research shows stent savings come from
      negotiations, not implementations.

PMID- 16792240
TI  - New growth references for assessment of stature and skeletal maturation in
      Australians.
AB  - BACKGROUND: We have provided evidence of secular increases in stature and
      acceleration of skeletal maturation in Australian male children and young adults
      in recent decades, and relatively less prominent secular increases in stature in
      females. AIMS: Our aims were to construct new references for stature and skeletal
      age in Australians. METHODS: We conducted a cross-sectional study of 2,497 South
      Australians, comprising 1,255 males and 1,242 females aged between 9 and 18
      years. Clinical records obtained from 1995 to 2005 comprised stature,
      chronological and skeletal ages of these individuals. Means and standard
      deviations for stature and skeletal age were visually smoothed for each sex to
      construct growth charts depicting the 97th, 90th, 75th, 50th, 25th, 10th and 3rd
      centiles. RESULTS: Comparisons of the new stature references with the NHMRC
      (1975) charts indicated an upward shift of stature centiles across all age groups
      in both sexes by around 4-5 cm. Generally, skeletally advanced individuals tended
      to be taller, and skeletally delayed individuals tended to be shorter compared
      with the total sample in younger age groups, but this was less apparent in older
      age groups. Males aged 9 years in our study were skeletally advanced, on average,
      by 0.4 years, whereas males aged 17 years were skeletally delayed, on average, by
      0.3 years compared with the Greulich and Pyle (1959) standards. In contrast,
      skeletal and chronological ages were concordant in females. CONCLUSION: Our new
      references for stature and skeletal age provide up-to-date information for
      orthodontists, paedodontists and paediatricians requiring growth data for young
      Australians.

PMID- 16792241
TI  - Tribological behaviour of orthodontic archwires under dry and wet sliding
      conditions in-vitro. I--Frictional behaviour.
AB  - OBJECTIVE: To evaluate the frictional behaviour of orthodontic archwires in dry
      and wet conditions in-vitro. METHODS: Two types of archwire materials were
      investigated: stainless steel and NiTi. A fretting wear tribometer fitted with an
      alumina ball was operated at 23 degrees C in three different environments:
      ambient air with 50 per cent relative humidity, 0.9 wt. per cent sodium chloride
      solution, and deionised water. RESULTS: NiTi archwires sliding against alumina
      exhibited high coefficients of friction (about 0.6) in the three environments.
      Stainless steel archwires sliding against alumina had relatively low coefficients
      of friction (0.3) in the solutions, but high coefficients (0.8) in air.
      CONCLUSION: The low frictional forces of the stainless steel wires sliding
      against alumina in the solutions were due to a lubricating effect of the
      solutions and corrosion-wear debris. The high frictional forces between the NiTi
      wires and alumina are attributed to an abrasive interfacial transfer film between
      the wires and alumina.

PMID- 16792242
TI  - Tribological behaviour of orthodontic archwires under dry and wet sliding
      conditions in-vitro. II--Wear patterns.
AB  - OBJECTIVE: To evaluate the wear patterns of orthodontic archwires in dry and wet
      conditions in-vitro. METHODS: The patterns of wear of stainless steel and NiTi
      orthodontic archwires were investigated with a fretting wear tribometer fitted
      with an alumina ball. The tribometer was operated at 23 degrees C in three
      different environments: ambient air with 50 per cent relative humidity (RH), 0.9
      wt. per cent sodium chloride solution and deionised water. Differences in the
      wear characteristics of the archwires were investigated by scanning electron
      microscopy. Energy Dispersive X-ray Analysis and Inductively Coupled Plasma
      Analysis were used to investigate the surface composition of the wires, the wear
      debris generated during fretting and the corrosion products in the test
      solutions. RESULTS: Both archwire materials were degraded by oxidational wear in
      ambient air. The NiTi wires were more resistant to wear than the stainless steel
      wires. In the aqueous media the stainless steel wires were degraded by abrasive
      wear, while the NiTi wires were degraded by adhesive wear. CONCLUSION: In ambient
      air with 50 per cent RH, NiTi wires were more resistant to wear than stainless
      steel wires. Both archwire materials exhibited higher wear rates in the solutions
      than in air, indicating some synergism between the wear and corrosion processes.
      In the solutions the stainless steel archwires had a much lower corrosion-wear
      resistance than the NiTi archwires.

PMID- 16792243
TI  - Effect of upper premolar extractions on the position of the upper lip.
AB  - BACKGROUND: It has been suggested that Class II division 1 malocclusions treated
      with extractions result in detrimental changes in the facial profile. This study
      investigates changes in the position of the upper lip following upper arch
      extractions only. OBJECTIVE: To investigate changes in the position of the upper
      lip following extraction of the upper first premolars and retraction of the upper
      incisors. METHODS: The sample consisted of 35 Class II division 1 patients with
      overjets of least 5 mm whose malocclusions were corrected with upper first
      premolar extractions and full fixed appliances. Twelve patients in the sample had
      overjets > or = 9 mm. There were no extractions in the lower arch. Pre- and post
      treatment lateral cephalograms were used to determine the changes in the position
      of the upper lip. RESULTS: At the end of treatment the upper lip was 0.46 mm less
      protrusive than at the start of treatment. In patients with overjets > or = 9 mm
      the upper lip was approximately 1 mm less protrusive at the end of treatment
      (Mean pre- and post-treatment difference: 0.92 mm). There were no significant
      gender differences in the positions of the upper lip. CONCLUSION: Minimal changes
      occur in the position of the upper lip following extraction of the upper
      premolars and retraction of the upper incisors. Factors other than the position
      of the upper incisors may determine the post-treatment position of the upper lip.

PMID- 16792244
TI  - A clinical comparison between nickel titanium springs and elastomeric chains.
AB  - OBJECTIVES: To compare the rates of maxillary canine retraction and molar
      anchorage loss when using either NiTi springs or elastomeric chains delivering a
      known force with sliding edgewise mechanics. METHODS: Twelve patients who
      required maxillary canine retraction into first premolar extraction sites as part
      of their orthodontic treatment were selected. In a split-mouth design, these
      patients received precalibrated NiTi springs (112 quadrants) and pre-measured
      elastomeric chains (12 quadrants), all delivering initial forces of approximately
      200 g and being reactivated at 28 day intervals. Space closure and forward
      movement of the maxillary first molars were evaluated using maxillary
      impressions, which were taken before the start of canine retraction and then at
      28 day intervals until canine retraction was almost complete. RESULTS:
      Statistical analysis revealed that the mean rate of space closure with NiTi
      springs (1.85 mm/month) was only 0.17 mm/month greater (p = 0.011) than that
      produced with the elastomeric chains (1.68 mm/month). The mean rates of anchorage
      loss for the NiTi springs and elastomeric chain were 0.46 mm/month and 0.45
      mm/month respectively. This difference was not statistically significant. These
      amounts of forward molar movement were calculated to be between one quarter and
      one third of the average space closure per month, even in the presence of a fixed
      transpalatal arch. CONCLUSION: The results indicate that the rates of space
      closure and molar anchorage loss using either NiTi springs or elastomeric chains,
      if reactivated every 28 days, are likely to be similar.

PMID- 16792245
TI  - Stature and skeletal maturation of two cohorts of Australian children and young
      adults over the past two decades.
AB  - BACKGROUND: Assessment of growth and maturation in humans has implications in the
      diagnosis and treatment of growth disorders and in determining timing of
      orthopaedic interventions. AIMS: Our aims were to investigate whether there was
      evidence of recent secular changes in stature and skeletal maturation in
      Australians, and to report any association between these parameters. METHODS: The
      cross-sectional study sample comprised 5,122 South Australian children and young
      adults, including 2,601 males and 2,521 females aged between 9 and 18 years.
      Records obtained from 1987 to 2005 included chronological age, stature and
      skeletal age in these individuals. Centiles for stature were calculated using the
      National Health and Medical Research Council of Australia (NHMRC) growth
      references published in 1975. Stature was measured to the nearest 0.1 cm and the
      developmental stages of strategic ossification centres on hand-wrist radiographs
      were evaluated using the Greulich and Pyle (1959) atlas method. RESULTS: Average
      values for stature were consistently greater in the 1995-2005 cohort compared
      with the 1987-94 cohort for both sexes, although secular increases in females
      were less prominent compared with males. Males in the 1995-2005 cohort were also
      skeletally advanced when compared with their counterparts in the 1987-94 cohort,
      but this trend was not evident in females. There were significant associations
      between stature and skeletal maturation, with the strongest associations being
      noted around puberty in both sexes and progressively weaker associations in older
      age groups. CONCLUSION: Our findings indicate secular increases in stature in
      Australian children and young adults of both sexes over the past few decades, and
      acceleration of skeletal maturation in males.

PMID- 16792248
TI  - Evidence-bolstered orthodontics.

PMID- 16792246
TI  - Effects of surface treatment on orthodontic bonding to amalgam.
AB  - AIM: This study aimed to compare the shear bond strengths of metal brackets
      bonded to amalgam surfaces. METHODS: One hundred and fifty amalgam samples were
      fabricated and either polished, roughened with a diamond bur or sandblasted with
      50 mm aluminium oxide. Following thermocycling the shear bond strengths were
      tested and compared with control samples bonded to etched enamel. RESULTS:
      Concise resin composite, Metal Primer/Concise resin composite and All-Bond
      II/Concise resin composite bonded to sandblasted amalgam gave the highest mean
      shear strengths and were statistically similar to the etched enamel/Concise resin
      composite controls. CONCLUSION: One would expect sandblasted amalgam surfaces to
      be associated with higher shear bond strengths than diamond bur roughened or
      polished amalgam surfaces.

PMID- 16792247
TI  - Mandibular arch changes following nonextraction treatment.

PMID- 16792249
TI  - Can we justify a global model of facial attractiveness and beauty?

PMID- 16792250
TI  - Improved patient education and practice efficiency via digital radiography--Part
      I.

PMID- 16792251
TI  - Using provisional restorations to improve results in complex aesthetic
      restorative cases.
AB  - Provisional restorations provide more than an intermediate functional and
      protective covering of teeth that have been prepared for indirect restorations.
      They provide the opportunity to build a relationship with the patient, to more
      clearly achieve the patient's aesthetic expectations, to build patient hygiene
      skills and habits, and to learn what is ideal for patients occlusally,
      phonetically, and aesthetically. This presentation examines the benefits of
      provisionalization and how to effectively communicate the information learned in
      this stage to the laboratory for replication in the definitive restorations.
      LEARNING OBJECTIVES: This article demonstrates how provisional restorations can
      be used to build a collaborative relationship between the prosthodontist,
      patient, dental specialists, and laboratory technician. Upon reading this
      article, the reader should: Understand how to use provisional restorations to
      develop patient expectations and to build a clear understanding of treatment
      goals. Understand how provisional restorations can be used to limit occlusal and
      phonetic difficulties that can occur in these restorations.

PMID- 16792252
TI  - A biomodification of tooth discoloration.

PMID- 16792253
TI  - Clinical use of the Er,Cr: YSGG laser for osseous crown lengthening: redefining
      the standard of care.
AB  - To design the optimal outcome for a patient during aesthetic enhancement, the
      restorative dentist must seek to create a symmetrical and harmonious relationship
      between the lips, gingival architecture, and the positions of the natural dentate
      forms. In the author's experience, the Er,Cr: YSGG laser has been a useful
      adjunct for performing aesthetic surgical crown lengthening procedures. This
      article will highlight the associated biological principles and demonstrate
      techniques for the application of this laser in closed and open crown lengthening
      procedures. LEARNING OBJECTIVES: This article demonstrates the use of the Er,Cr:
      YSGG laser for osseous crown lengthening . Upon reading this article, the reader
      should have: Enhanced awareness of criteria for developing a biologically stable
      free gingival margin. Greater familiarity with the open and closed crown
      lengthening procedures, including case selection and surgical approaches.

PMID- 16792254
TI  - Use of the Er,Cr: YSGG laser to improve periodontal plastic surgery: the
      periodontist's perspective.

PMID- 16792255
TI  - Treatment planning and smile design using composite resin.
AB  - Recent advances in dental materials and adhesive protocols have expanded the
      restorative procedures available to today's clinicians. Used in combination with
      proper treatment planning, these innovations enable dental professionals to
      provide enhanced aesthetic care that achieves the increasing expectations of
      their patients. Using a case presentation, this article will document the steps
      required to harmoniously integrate smile design, material selection, and patient
      communication that are involved in the provisional of aesthetic dental care.
      LEARNING OBJECTIVES: This article discusses the utilization of composite resin as
      a tool to enhance the patient's smile. Upon reading this article, the reader
      should: Become familiar with a smile-enhancing technique which can be completed
      in one office visit. Realize the benefits that intraoral composite mockups offer
      in terms of prototyping and confirming patient satisfaction.

PMID- 16792256
TI  - The palatal press and roll anesthesia technique.

PMID- 16792257
TI  - The use of glass ionomers as a chemical treatment for caries.

PMID- 16792258
TI  - Improving implant aesthetics: prosthetically generated papilla through tissue
      modeling with composite.
AB  - Dental implants provide clinicians with a predictable means of replacing the
      function of lost natural teeth. Whereas innovative restorative materials and
      techniques have yielded predictable "white aesthetics" for a tooth, comparable
      success with the "pink aesthetics" of implant restorations has been more
      problematic. This article describes a technique for improving the aesthetic
      outcome of implant dentistry by contouring soft tissue around implants through a
      buildup of composite to a "UCLA-type" abutment. From this technique, it is
      believed that a similar procedure for other implant systems can be easily and
      successfully extrapolated. LEARNING OBJECTIVES: This article discusses a
      technique that allows for implant placement in cases where the emergence profile
      has been compromised. Upon reading this article, the reader should: Understand
      why the pink aesthetics of the patient's smile are as important as the "white
      aesthetics". Learn how to contour the soft tissues surrounding implants.

PMID- 16792259
TI  - Fearless in Spartanburg. Small S.C. system's antitrust lawsuit against giant
      bedmaker ends 'bundling,' reaps dollar 337 million in national settlement.
AB  - The head of a small hospital system in South Carolina thought there was something
      wrong with Hill-Rom's pricing policies. Now that system and some 3,000 other
      hospitals await a hearing this week on the proposed dollar 337.5 million class
      action settlement reached with the bedmaker. Patrick de Maynadier, left, of Hill
      Rom, says his company has discontinued the "bundling" practices contested in the
      lawsuit.

PMID- 16792260
TI  - Citizens want more from care. Americans see differently on Bush healthcare
      policies.

PMID- 16792261
TI  - Looking for more time. Providers want longer wait before new PPS starts.

PMID- 16792262
TI  - CHA readies for revenue drop. Lowered fees a relief for members facing bad debt.

PMID- 16792263
TI  - It's all up to the JCAHO. Outside groups won't determine O'Learry's successor.

PMID- 16792264
TI  - Docs use more tech... But many of them lack sophisticated systems.

PMID- 16792265
TI  - Supreme Court turns down PBMs. Fight continues over disclosure of drug discounts.

PMID- 16792266
TI  - NRHA to launch fellows program.

PMID- 16792267
TI  - Brockovich takes on healthcare. Several lawsuits allege wrongful billing of
      Medicare.

PMID- 16792268
TI  - Making research pay. Reaping rewards, conflicts for developing drugs.

PMID- 16792269
TI  - LifePoint gets good with bad. Four-hospital buy includes two it plans on
      reselling.

PMID- 16792270
TI  - A JCAHO for patients. O'Leary's departure opens door to its rebirth as a
      regulator without conflicts.

PMID- 16792271
TI  - Evidence-based prevention. New research finds big payoff in low-cost, pedestrian
      interventions.

PMID- 16792272
TI  - In good health, at least for now. Health systems report another strong year in
      2005, but rising bad debt and concerns over reimbursement weigh on prognosis.

PMID- 16792273
TI  - It takes a community. Rural hospitals may have an edge in improving population
      health.

PMID- 16792274
TI  - Docs revive small hospital. By concentrating on imaging, owners put former county
      facility in the black.

PMID- 16792275
TI  - The Third International Meeting on Brain-Computer Interface Technology: making a
      difference.
AB  - This special issue of the IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION
      ENGINEERING provides a representative and comprehensive bird's-eye view of the
      most recent developments in brain-computer interface (BCI) technology from
      laboratories around the world. The 30 research communications and papers are the
      direct outcome of the Third International Meeting on Brain-Computer Interface
      Technology held at the Rensselaerville Institute, Rensselaerville, NY, in June
      2005. Fifty-three research groups from North and South America, Europe, and Asia,
      representing the majority of all the existing BCI laboratories around the world,
      participated in this highly focused meeting sponsored by the National Institutes
      of Health and organized by the BCI Laboratory of the Wadsworth Center of the New
      York State Department of Health. As demonstrated by the papers in this special
      issue, the rapid advances in BCI research and development make this technology
      capable of providing communication and control to people severely disabled by
      amyotrophic lateral sclerosis (ALS), brainstem stroke, cerebral palsy, and other
      neuromuscular disorders. Future work is expected to improve the performance and
      utility of BCIs, and to focus increasingly on making them a viable, practical,
      and affordable communication alternative for many thousands of severely disabled
      people worldwide.

PMID- 16792276
TI  - BCI meeting 2005--workshop on technology: hardware and software.
AB  - This paper describes the outcome of discussions held during the Third
      International BCI Meeting at a workshop to review and evaluate the current state
      of BCI-related hardware and software. Technical requirements and current
      technologies, standardization procedures and future trends are covered. The main
      conclusion was recognition of the need to focus technical requirements on the
      users' needs and the need for consistent standards in BCI research.

PMID- 16792277
TI  - BCI Meeting 2005--workshop on clinical issues and applications.
AB  - This paper describes the outcome of discussions held during the Third
      International BCI Meeting at a workshop charged with reviewing and evaluating the
      current state of and issues relevant to brain-computer interface (BCI) clinical
      applications. These include potential BCI users, applications, validation,
      getting BCIs to users, role of government and industry, plasticity, and ethics.

PMID- 16792278
TI  - BCI Meeting 2005--workshop on BCI signal processing: feature extraction and
      translation.
AB  - This paper describes the outcome of discussions held during the Third
      International BCI Meeting at a workshop charged with reviewing and evaluating the
      current state of and issues relevant to brain-computer interface (BCI) feature
      extraction and translation. The issues discussed include a taxonomy of methods
      and applications, time-frequency spatial analysis, optimization schemes, the role
      of insight in analysis, adaptation, and methods for quantifying BCI feedback.

PMID- 16792279
TI  - BCI Meeting 2005--workshop on signals and recording methods.
AB  - This paper describes the highlights of presentations and discussions during the
      Third International BCI Meeting in a workshop that evaluated potential brain
      computer interface (BCI) signals and currently available recording methods. It
      defined the main potential user populations and their needs, addressed the
      relative advantages and disadvantages of noninvasive and implanted (i.e.,
      invasive) methodologies, considered ethical issues, and focused on the challenges
      involved in translating BCI systems from the laboratory to widespread clinical
      use. The workshop stressed the critical importance of developing useful
      applications that establish the practical value of BCI technology.

PMID- 16792280
TI  - Geometric subspace methods and time-delay embedding for EEG artifact removal and
      classification.
AB  - Generalized singular-value decomposition is used to separate multichannel
      electroencephalogram (EEG) into components found by optimizing a signal-to-noise
      quotient. These components are used to filter out artifacts. Short-time principal
      components analysis of time-delay embedded EEG is used to represent windowed EEG
      data to classify EEG according to which mental task is being performed. Examples
      are presented of the filtering of various artifacts and results are shown of
      classification of EEG from five mental tasks using committees of decision trees.

PMID- 16792281
TI  - The Berlin Brain-Computer Interface: EEG-based communication without subject
      training.
AB  - The Berlin Brain-Computer Interface (BBCI) project develops a noninvasive BCI
      system whose key features are 1) the use of well-established motor competences as
      control paradigms, 2) high-dimensional features from 128-channel
      electroencephalogram (EEG), and 3) advanced machine learning techniques. As
      reported earlier, our experiments demonstrate that very high information transfer
      rates can be achieved using the readiness potential (RP) when predicting the
      laterality of upcoming left- versus right-hand movements in healthy subjects. A
      more recent study showed that the RP similarily accompanies phantom movements in
      arm amputees, but the signal strength decreases with longer loss of the limb. In
      a complementary approach, oscillatory features are used to discriminate imagined
      movements (left hand versus right hand versus foot). In a recent feedback study
      with six healthy subjects with no or very little experience with BCI control,
      three subjects achieved an information transfer rate above 35 bits per minute
      (bpm), and further two subjects above 24 and 15 bpm, while one subject could not
      achieve any BCI control. These results are encouraging for an EEG-based BCI
      system in untrained subjects that is independent of peripheral nervous system
      activity and does not rely on evoked potentials even when compared to results
      with very well-trained subjects operating other BCI systems.

PMID- 16792282
TI  - The BCI competition. III: Validating alternative approaches to actual BCI
      problems.
AB  - A brain-computer interface (BCI) is a system that allows its users to control
      external devices with brain activity. Although the proof-of-concept was given
      decades ago, the reliable translation of user intent into device control commands
      is still a major challenge. Success requires the effective interaction of two
      adaptive controllers: the user's brain, which produces brain activity that
      encodes intent, and the BCI system, which translates that activity into device
      control commands. In order to facilitate this interaction, many laboratories are
      exploring a variety of signal analysis techniques to improve the adaptation of
      the BCI system to the user. In the literature, many machine learning and pattern
      classification algorithms have been reported to give impressive results when
      applied to BCI data in offline analyses. However, it is more difficult to
      evaluate their relative value for actual online use. BCI data competitions have
      been organized to provide objective formal evaluations of alternative methods.
      Prompted by the great interest in the first two BCI Competitions, we organized
      the third BCI Competition to address several of the most difficult and important
      analysis problems in BCI research. The paper describes the data sets that were
      provided to the competitors and gives an overview of the results.

PMID- 16792283
TI  - Brain interface research for asynchronous control applications.
AB  - The Neil Squire Society has developed asynchronous, direct brain switches for
      self-paced control applications with mean activation rates of 73% and false
      positive error rates of 2%. This report summarizes our results to date, lessons
      learned, and current directions, including research into implanted brain
      interface designs.

PMID- 16792284
TI  - Towards a robust BCI: error potentials and online learning.
AB  - Recent advances in the field of brain-computer interfaces (BCIs) have shown that
      BCIs have the potential to provide a powerful new channel of communication,
      completely independent of muscular and nervous systems. However, while there have
      been successful laboratory demonstrations, there are still issues that need to be
      addressed before BCIs can be used by nonexperts outside the laboratory. At IDIAP
      Research Institute, we have been investigating several areas that we believe will
      allow us to improve the robustness, flexibility, and reliability of BCIs. One
      area is recognition of cognitive error states, that is, identifying errors
      through the brain's reaction to mistakes. The production of these error
      potentials (ErrP) in reaction to an error made by the user is well established.
      We have extended this work by identifying a similar but distinct ErrP that is
      generated in response to an error made by the interface, (a misinterpretation of
      a command that the user has given). This ErrP can be satisfactorily identified in
      single trials and can be demonstrated to improve the theoretical performance of a
      BCI. A second area of research is online adaptation of the classifier. BCI
      signals change over time, both between sessions and within a single session, due
      to a number of factors. This means that a classifier trained on data from a
      previous session will probably not be optimal for a new session. In this paper,
      we present preliminary results from our investigations into supervised online
      learning that can be applied in the initial training phase. We also discuss the
      future direction of this research, including the combination of these two
      currently separate issues to create a potentially very powerful BCI.

PMID- 16792285
TI  - Prolonged cognitive planning time, elevated cognitive effort, and relationship to
      coordination and motor control following stroke.
AB  - Understanding cortical function can provide accurately targeted interventions
      after stroke. Initially, stroke survivors had prolonged cognitive planning time
      and elevated cognitive effort, highly correlated with motor control impairments.
      Exploratory results suggest that neurorehabilitation, accurately targeted to
      dyscoordination, weakness, and dysfunctional task component execution, can
      improve cognitive processes controlling motor function.

PMID- 16792286
TI  - Neural ensemble activity from multiple brain regions predicts kinematic and
      dynamic variables in a multiple force field reaching task.
AB  - In everyday life, we reach, grasp, and manipulate a variety of different objects
      all with their own dynamic properties. This degree of adaptability is essential
      for a brain-controlled prosthetic arm to work in the real world. In this study,
      rats were trained to make reaching movements while holding a torque manipulandum
      working against two distinct loads. Neural recordings obtained from arrays of 32
      microelectrodes spanning the motor cortex were used to predict several movement
      related variables. In this paper, we demonstrate that a simple linear regression
      model can translate neural activity into endpoint position of a robotic
      manipulandum even while the animal controlling it works against different loads.
      A second regression model can predict, with 100% accuracy, which of the two loads
      is being manipulated by the animal. Finally, a third model predicts the work
      needed to move the manipulandum endpoint. This prediction is significantly better
      than that for position. In each case, the regression model uses a single set of
      weights. Thus, the neural ensemble is capable of providing the information
      necessary to compensate for at least two distinct load conditions.

PMID- 16792287
TI  - Cortically coupled computer vision for rapid image search.
AB  - We describe a real-time electroencephalography (EEG)-based brain-computer
      interface system for triaging imagery presented using rapid serial visual
      presentation. A target image in a sequence of nontarget distractor images elicits
      in the EEG a stereotypical spatiotemporal response, which can be detected. A
      pattern classifier uses this response to reprioritize the image sequence, placing
      detected targets in the front of an image stack. We use single-trial analysis
      based on linear discrimination to recover spatial components that reflect
      differences in EEG activity evoked by target versus nontarget images. We find an
      optimal set of spatial weights for 59 EEG sensors within a sliding 50-ms time
      window. Using this simple classifier allows us to process EEG in real time. The
      detection accuracy across five subjects is on average 92%, i.e., in a sequence of
      2500 images, resorting images based on detector output results in 92% of target
      images being moved from a random position in the sequence to one of the first 250
      images (first 10% of the sequence). The approach leverages the highly robust and
      invariant object recognition capabilities of the human visual system, using
      single-trial EEG analysis to efficiently detect neural signatures correlated with
      the recognition event.

PMID- 16792288
TI  - Local field potential spectral tuning in motor cortex during reaching.
AB  - In this paper, intracortical local field potentials (LFPs) and single units were
      recorded from the motor cortices of monkeys (Macaca fascicularis) while they
      preformed a standard three-dimensional (3-D) center-out reaching task. During the
      center-out task, the subjects held their hands at the location of a central
      target and then reached to one of eight peripheral targets forming the corners of
      a virtual cube. The spectral amplitudes of the recorded LFPs were calculated,
      with the high-frequency LFP (HF-LFP) defined as the average spectral amplitude
      change from baseline from 60 to 200 Hz. A 3-D linear regression across the eight
      center-out targets revealed that approximately 6% of the beta LFPs (18-26 Hz) and
      18% of the HF-LFPs were tuned for velocity (p-value < 0.05), while 10% of the
      beta LFPs and 15% of the HF-LFPs were tuned for position. These results suggest
      that a multidegree-of-freedom brain-machine interface is possible using high
      frequency LFP recordings in motor cortex.

PMID- 16792289
TI  - Classifying EEG and ECoG signals without subject training for fast BCI
      implementation: comparison of nonparalyzed and completely paralyzed subjects.
AB  - We summarize results from a series of related studies that aim to develop a motor
      imagery-based brain-computer interface using a single recording session of
      electroencephalogram (EEG) or electrocorticogram (ECoG) signals for each subject.
      We apply the same experimental and analytical methods to 11 nonparalysed subjects
      (eight EEG, three ECoG), and to five paralyzed subjects (four EEG, one ECoG) who
      had been unable to communicate for some time. While it was relatively easy to
      obtain classifiable signals quickly from most of the nonparalyzed subjects, it
      proved impossible to classify the signals obtained from the paralyzed patients by
      the same methods. This highlights the fact that though certain BCI paradigms may
      work well with healthy subjects, this does not necessarily indicate success with
      the target user group. We outline possible reasons for this failure to transfer.

PMID- 16792290
TI  - The Neurochip BCI: towards a neural prosthesis for upper limb function.
AB  - The Neurochip BCI is an autonomously operating interface between an implanted
      computer chip and recording and stimulating electrodes in the nervous system. By
      converting neural activity recorded in one brain area into electrical stimuli
      delivered to another site, the Neurochip BCI could form the basis for a simple,
      direct neural prosthetic. In tests with normal, unrestrained monkeys, the
      Neurochip continuously recorded activity of single neurons in primary motor
      cortex for several weeks at a time. Cortical activity was correlated with
      simultaneously-recorded electromyogram (EMG) activity from arm muscles during
      free behavior. In separate experiments with anesthetized monkeys, we found that
      microstimulation of the cervical spinal cord evoked movements of the arm and
      hand, often involving multiple muscles synergies. These observations suggest that
      spinal microstimulation controlled by cortical neurons could help compensate for
      damaged corticospinal projections.

PMID- 16792291
TI  - EEG and MEG brain-computer interface for tetraplegic patients.
AB  - We characterized features of magnetoencephalographic (MEG) and
      electroencephalographic (EEG) signals generated in the sensorimotor cortex of
      three tetraplegics attempting index finger movements. Single MEG and EEG trials
      were classified offline into two classes using two different classifiers, a batch
      trained classifier and a dynamic classifier. Classification accuracies obtained
      with dynamic classifier were better, at 75%, 89%, and 91% in different subjects,
      when features were in the 0.5-3.0-Hz frequency band. Classification accuracies of
      EEG and MEG did not differ.

PMID- 16792292
TI  - Electrocorticography-based brain computer interface--the Seattle experience.
AB  - Electrocorticography (ECoG) has been demonstrated to be an effective modality as
      a platform for brain-computer interfaces (BCIs). Through our experience with ten
      subjects, we further demonstrate evidence to support the power and flexibility of
      this signal for BCI usage. In a subset of four patients, closed-loop BCI
      experiments were attempted with the patient receiving online feedback that
      consisted of one-dimensional cursor movement controlled by ECoG features that had
      shown correlation with various real and imagined motor and speech tasks. All four
      achieved control, with final target accuracies between 73%-100%. We assess the
      methods for achieving control and the manner in which enhancing online control
      can be accomplished by rescreening during online tasks. Additionally, we assess
      the relevant issues of the current experimental paradigm in light of their
      clinical constraints.

PMID- 16792293
TI  - Could cortical signals control intraspinal stimulators? A theoretical evaluation.
AB  - In this paper, we examine the control signals that are required to generate
      stepping using two different intraspinal microstimulation (ISMS) paradigms and
      discuss the theoretical feasibility of controlling ISMS-evoked stepping using a
      brain computer interface. Tonic (constant amplitude) and phasic (modulated
      amplitude) ISMS protocols were used to produce stepping in the hind limbs of
      paralyzed cats. Low-amplitude tonic ISMS activated a spinal locomotor-like
      network that resulted in bilateral stepping of the hind limbs. Phasic ISMS
      generated coordinated stepping by simultaneously activating flexor synergies in
      one limb coupled with extensor synergies in the other. Using these ISMS
      paradigms, we propose that one or two independent cortical signals will be
      adequate for controlling ISMS-induced stepping after SCI.

PMID- 16792294
TI  - EEG based BCI-towards a better control. Brain-computer interface research at
      Aalborg University.
AB  - This paper summarizes the brain-computer interface (BCI)-related research being
      conducted at Aalborg University. Namely, an online synchronized BCI system using
      steady-state visual evoked potentials, and investigations on cortical modulation
      of movement-related parameters are presented.

PMID- 16792295
TI  - 15 years of BCI research at Graz University of Technology: current projects.
AB  - Over the last 15 years, the Graz Brain-Computer Interface (BCI) has been
      developed and all components such as feature extraction and classification, mode
      of operation, mental strategy, and type of feedback have been investigated.
      Recent projects deal with the development of asynchronous BCIs, the presentation
      of feedback and applications for communication and control.

PMID- 16792296
TI  - Brain-computer interaction research at the Computer Vision and Multimedia
      Laboratory, University of Geneva.
AB  - This paper describes the work being conducted in the domain of brain-computer
      interaction (BCI) at the Multimodal Interaction Group, Computer Vision and
      Multimedia Laboratory, University of Geneva, Geneva, Switzerland. The application
      focus of this work is on multimodal interaction rather than on rehabilitation,
      that is how to augment classical interaction by means of physiological
      measurements. Three main research topics are addressed. The first one concerns
      the more general problem of brain source activity recognition from EEGs. In
      contrast with classical deterministic approaches, we studied iterative robust
      stochastic based reconstruction procedures modeling source and noise statistics,
      to overcome known limitations of current techniques. We also developed procedures
      for optimal electroencephalogram (EEG) sensor system design in terms of placement
      and number of electrodes. The second topic is the study of BCI protocols and
      performance from an information-theoretic point of view. Various information rate
      measurements have been compared for assessing BCI abilities. The third research
      topic concerns the use of EEG and other physiological signals for assessing a
      user's emotional status.

PMID- 16792297
TI  - Towards human BCI applications based on cognitive brain systems: an investigation
      of neural signals recorded from the dorsolateral prefrontal cortex.
AB  - One of the critical issues in brain-computer interface (BCI) research is how to
      translate a person's intention into brain signals for controlling computer
      programs. The motor system is currently the primary focus, where signals are
      obtained during imagined motor responses. However, cognitive brain systems are
      also attractive candidates, in that they may be more amenable to conscious
      control, yielding better regulation of magnitude and duration of localized brain
      activity. We report on a proof of principle study for the potential use of a
      higher cognitive system for BCI, namely the working memory (WM) system. We show
      that mental calculation reliably activates the WM network as measured with
      functional magnetic resonance imaging (fMRI). Moreover, activity in the
      dorsolateral prefrontal cortex (DLPFC) indicates that this region is active for
      the duration of mental processing. This supports the notion that DLPFC can be
      activated, and remains active, at will. Further confirmation is obtained from a
      patient with an implanted electrode grid for diagnostic purposes, in that gamma
      power within DLPFC increases during mental calculation and remains elevated for
      the duration thereof. These results indicate that cortical regions involved in
      higher cognitive functions may serve as a readily self-controllable input for BCI
      applications. It also shows that fMRI is an effective tool for identifying
      function-specific foci in individual subjects for subsequent placement of
      cortical electrodes. The fact that electrocorticographic (ECoG) signal confirmed
      the functional localization of fMRI provides a strong argument for incorporating
      fMRI in BCI research.

PMID- 16792298
TI  - Structural modifications in chronic microwire electrodes for cortical
      neuroprosthetics: a case study.
AB  - Long-term viability of chronic invasive neural probes is a necessary condition
      for extracting robust control signals directly from neural tissue. Although
      immune/tissue response is a leading factor in the degradation of single neuron
      recording, we investigate a second component of signal degradation connected to
      the structural changes associated with microwire electrodes chronically exposed
      to extracelluar environments in vivo. Scanning electron microscopy is used to
      assess the surface modifications to the electrodes after an implantation duration
      of four weeks in rats. The electrode developed a smooth fracture surface, a
      reduction of the metal diameter, and pitting in the insulation of the electrode
      structure. Over the duration of implantation, recording properties of the
      electrode were marked by a reduction in the peak-to-peak amplitude in neuronal
      firing.

PMID- 16792299
TI  - Brain-computer interface research at the University of South Florida Cognitive
      Psychophysiology Laboratory: the P300 Speller.
AB  - We describe current efforts to implement and improve P300-BCI communication
      tools. The P300 Speller first described by Farwell and Donchin (in 1988) adapted
      the so-called oddball paradigm (OP) as the operating principle of the brain
      computer interface (BCI) and was the first P300-BCI. The system operated by
      briefly intensifying each row and column of a matrix and the attended row and
      column elicited a P300 response. This paradigm has been the benchmark in P300-BCI
      systems, and in the past few years the P300 Speller paradigm has been solidified
      as a promising communication tool. While promising, we have found that some
      people who have amyotrophic lateral sclerosis (ALS) would be better suited with a
      system that has a limited number of choices, particularly if the 6 x 6 matrix is
      difficult to use. Therefore, we used the OP to implement a four-choice system
      using the commands: Yes, No, Pass, and End; we also used three presentation
      modes: auditory, visual, and auditory and visual. We summarize results from both
      paradigms and also discuss obstacles we have identified while working with the
      ALS population outside of the laboratory environment.

PMID- 16792300
TI  - Brain-computer interfaces for 1-D and 2-D cursor control: designs using
      volitional control of the EEG spectrum or steady-state visual evoked potentials.
AB  - We have developed and tested two electroencephalogram (EEG)-based brain-computer
      interfaces (BCI) for users to control a cursor on a computer display. Our system
      uses an adaptive algorithm, based on kernel partial least squares classification
      (KPLS), to associate patterns in multichannel EEG frequency spectra with cursor
      controls. Our first BCI, Target Practice, is a system for one-dimensional device
      control, in which participants use biofeedback to learn voluntary control of
      their EEG spectra. Target Practice uses a KPLS classifier to map power spectra of
      62-electrode EEG signals to rightward or leftward position of a moving cursor on
      a computer display. Three subjects learned to control motion of a cursor on a
      video display in multiple blocks of 60 trials over periods of up to six weeks.
      The best subject's average skill in correct selection of the cursor direction
      grew from 58% to 88% after 13 training sessions. Target Practice also implements
      online control of two artifact sources: 1) removal of ocular artifact by linear
      subtraction of wavelet-smoothed vertical and horizontal electrooculograms (EOG)
      signals, 2) control of muscle artifact by inhibition of BCI training during
      periods of relatively high power in the 40-64 Hz band. The second BCI, Think
      Pointer, is a system for two-dimensional cursor control. Steady-state visual
      evoked potentials (SSVEP) are triggered by four flickering checkerboard stimuli
      located in narrow strips at each edge of the display. The user attends to one of
      the four beacons to initiate motion in the desired direction. The SSVEP signals
      are recorded from 12 electrodes located over the occipital region. A KPLS
      classifier is individually calibrated to map multichannel frequency bands of the
      SSVEP signals to right-left or up-down motion of a cursor on a computer display.
      The display stops moving when the user attends to a central fixation point. As
      for Target Practice, Think Pointer also implements wavelet-based online removal
      of ocular artifact; however, in Think Pointer muscle artifact is controlled via
      adaptive normalization of the SSVEP. Training of the classifier requires about 3
      min. We have tested our system in real-time operation in three human subjects.
      Across subjects and sessions, control accuracy ranged from 80% to 100% correct
      with lags of 1-5 s for movement initiation and turning. We have also developed a
      realistic demonstration of our system for control of a moving map display
      (http://ti.arc.nasa.gov/).

PMID- 16792301
TI  - The Wadsworth BCI Research and Development Program: at home with BCI.
AB  - The ultimate goal of brain-computer interface (BCI) technology is to provide
      communication and control capacities to people with severe motor disabilities.
      BCI research at the Wadsworth Center focuses primarily on noninvasive,
      electroencephalography (EEG)-based BCI methods. We have shown that people,
      including those with severe motor disabilities, can learn to use sensorimotor
      rhythms (SMRs) to move a cursor rapidly and accurately in one or two dimensions.
      We have also improved P300-based BCI operation. We are now translating this
      laboratory-proven BCI technology into a system that can be used by severely
      disabled people in their homes with minimal ongoing technical oversight. To
      accomplish this, we have: improved our general-purpose BCI software (BCI2000);
      improved online adaptation and feature translation for SMR-based BCI operation;
      improved the accuracy and bandwidth of P300-based BCI operation; reduced the
      complexity of system hardware and software and begun to evaluate home system use
      in appropriate users. These developments have resulted in prototype systems for
      every day use in people's homes.

PMID- 16792302
TI  - A practical VEP-based brain-computer interface.
AB  - This paper introduces the development of a practical brain-computer interface at
      Tsinghua University. The system uses frequency-coded steady-state visual evoked
      potentials to determine the gaze direction of the user. To ensure more universal
      applicability of the system, approaches for reducing user variation on system
      performance have been proposed. The information transfer rate (ITR) has been
      evaluated both in the laboratory and at the Rehabilitation Center of China,
      respectively. The system has been proved to be applicable to > 90% of people with
      a high ITR in living environments.

PMID- 16792303
TI  - Decoding sensory feedback from firing rates of afferent ensembles recorded in cat
      dorsal root ganglia in normal locomotion.
AB  - Sensory feedback is required by biological motor control systems to maintain
      stability, respond to perturbations, and adapt. Similarly, motor neuroprostheses
      require feedback to provide natural and complete restoration of motor functions.
      In this paper, we show that ensemble firing rates from the body's
      mechanoreceptors can provide a natural source of kinematic state feedback and
      could be useful for prosthetic control. Single unit recordings from multiple
      primary afferent neurons were obtained during walking using multichannel
      electrode arrays implanted chronically in the L7 dorsal root ganglia of three
      cats. We typically recorded simultaneously from over 20-30 neurons during the
      first 7-14 days after surgery, but recordings gradually worsened thereafter.
      Histology indicates that a ring of inflammatory and connective tissues (100
      microm thick) develops around each microelectrode and likely contributes to the
      degradation in recording quality. Accurate estimates of the hindlimb trajectory
      were made using a linear filter with inputs from only a few neurons highly
      correlated with limb kinematics. The coefficients for the linear filter were
      identified in a least-squares fit with 5-10 s of walking data (model training
      stage). The estimated and actual trajectories of separate walking data generally
      match well for walking at a range of speeds accounting for 63 +/- 22% (mean +/-
      S.D. for hip, knee, and ankle) of the variance in joint angle and 72 +/- 4% of
      the variance in joint angular velocities. These results indicate that a neural
      interface with primary sensory neurons in the dorsal root ganglion can provide
      accurate kinematic state information that may be useful for closed loop control
      of a neuroprosthesis.

PMID- 16792304
TI  - DASHER--an efficient writing system for brain-computer interfaces?
AB  - DASHER is a human-computer interface for entering text using continuous or
      discrete gestures. Through its use of an internal language model, DASHER
      efficiently converts bits received from the user into text, and has been shown to
      be a competitive alternative to existing text-entry methods in situations where
      an ordinary keyboard cannot be used. We propose that DASHER would be well-matched
      to the low bit-rate, noisy output obtained from brain-computer interfaces (BCIs),
      and discuss the issues surrounding the use of DASHER with BCI systems.

PMID- 16792305
TI  - ECoG factors underlying multimodal control of a brain-computer interface.
AB  - Most current brain-computer interface (BCI) systems for humans use
      electroencephalographic activity recorded from the scalp, and may be limited in
      many ways. Electrocorticography (ECoG) is believed to be a minimally-invasive
      alternative to electroencephalogram (EEG) for BCI systems, yielding superior
      signal characteristics that could allow rapid user training and faster
      communication rates. In addition, our preliminary results suggest that brain
      regions other than the sensorimotor cortex, such as auditory cortex, may be
      trained to control a BCI system using similar methods as those used to train
      motor regions of the brain. This could prove to be vital for users who have
      neurological disease, head trauma, or other conditions precluding the use of
      sensorimotor cortex for BCI control.

PMID- 16792306
TI  - An enhanced time-frequency-spatial approach for motor imagery classification.
AB  - Human motor imagery (MI) tasks evoke electroencephalogram (EEG) signal changes.
      The features of these changes appear as subject-specific temporal traces of EEG
      rhythmic components at specific channels located over the scalp. Accurate
      classification of MI tasks based upon EEG may lead to a noninvasive brain
      computer interface (BCI) to decode and convey intention of human subjects. We
      have previously proposed two novel methods on time-frequency feature extraction,
      expression and classification for high-density EEG recordings (Wang and He 2004;
      Wang, Deng, and He, 2004). In the present study, we refined the above time
      frequency-spatial approach and applied it to a one-dimensional "cursor control"
      BCI experiment with online feedback. Through offline analysis of the collected
      data, we evaluated the capability of the present refined method in comparison
      with the original time-frequency-spatial methods. The enhanced performance in
      terms of classification accuracy was found for the proposed approach, with a mean
      accuracy rate of 91.1% for two subjects studied.

PMID- 16792307
TI  - [Petr Ivanovich D'iakonov (1855-1908)].

PMID- 16792308
TI  - [The significance of investigation of the left ventricle diastolic function in
      cardiosurgery].
AB  - An examination of 79 patients (main group) with congenital, acquired heart
      diseases and ischemic heart disease (IHD) without activity of the rheumatoid
      process and infectious endocarditis and 64 subjects of the same age has shown
      that in order to improve the assessment of the results of operative treatment of
      patients with the acquired heart disease and IHD it is necessary to test the
      diastolic function of the left ventricle (LV) in addition to the systole
      parameters. Cardiosurgical correction of pathological processes either causing or
      aggravating LV diastolic dysfunction (overloading LV with the volume or pressure,
      myocardium ischemia) can either eliminate or reduce its degree. A pathological
      monophasic filling of LV is a sign of a pronounced systole-diastolic dysfunction
      of LV and lung hypertension. A radical operative intervention reestablishes the
      biphasic filling of LV and reduces pressure in the pulmonary artery.

PMID- 16792309
TI  - [Nutrition of patients operated for complicated gastroduodenal ulcers at the
      early postoperative period].
AB  - The investigation is based on an analysis of results of treatment of 102 patients
      after an emergency resection of the stomach for complicated gastroduodenal
      ulcers. The probe was inserted into the jejunum intraoperatively. The period of
      enteral probe nutrition (EPN) was 5-7 days. At the early postoperative period in
      patients who had undergone the emergency resection of the stomach EPN is an
      effective method of nutrition maintenance as compared with the infusion
      transfusion therapy. The method is simple and open to general use, and is
      economically advantageous under conditions of any hospital.

PMID- 16792310
TI  - [Immunological estimation of the degree and prognosis of acute pancreatitis].
AB  - An analysis of data of immunological investigation of blood of 89 patients with a
      severe acute pancreatitis (SAP) on the 2-3 day of the disease has revealed
      changes in immunogram characteristic also of other pathological conditions and
      pointing to a systemic inflammatory reaction. Among the patients who did not have
      purulent complications against the background of therapy of SAP, the character
      and degree of changes in immunogram were in line with average values, and so they
      could be considered as "a norm of pathology". A system of scores of impairments
      of the immune response to the destructive process was developed for an objective
      evaluation of the immune status of patients with SAP. In patients with a normal
      physiological immune response (sum of scores 0-5) the prognosis of the disease is
      considered to be good. No immunocorrectors should be included in the complex of
      treatment measures. In patients with an inadequate pathological immune response
      (sum of scores 9 and more) the prognosis is unfavorable. The complex of treatment
      measures for such patients should include immunocorrectors.

PMID- 16792311
TI  - [Choice of a method of plasty of the anterior abdominal wall in patients with
      postoperative ventral hernias].
AB  - The individual characteristics of the structure of the anterior abdominal wall
      were studied for revealing the anatomical preconditions for the formation of
      postoperative ventral hernias in order to substantiate efficient methods of
      surgical treatment. It was established that patients with brachiomorphous build
      had anatomical features facilitating the formation of ventral hernias. The
      greatest strength of the fascio-aponeurotic complex of the anterior abdominal
      wall is characteristic of patients with a dolichomorphous constitution, while the
      least strength of the fascio-aponeurotic complex of the anterior abdominal wall
      is characteristic of patients with brachiomorphous constitution. Patients with
      the dolicho- and mesomorphous constitution having postoperative ventral hernias
      can undergo plasty of the hernial gates with the local tissues. Patients with
      brachiomorphous constitution after elimination of the postoperative ventral
      hernias need the strengthening of the anterior abdominal wall with cellular
      explants.

PMID- 16792312
TI  - [A comparative assessment of results of operative treatment of great and giant
      postoperative ventral hernias].
AB  - An experience with operative treatment of 498 patients aged from 18 to 78 years
      with great and giant postoperative ventral hernias is presented. The patients
      were divided into several groups according to the kind of surgical intervention.
      An analysis of the nearest and long-term results (from 1 to 15 years) has shown
      that the fewer number of postoperative complications and recurrences was after
      using an additional strengthening of the abdominal wall tissues with split and
      full-thickness autoplastic skin grafts as well as polypropilene net.
      Autodermotransplants are highly effective in use, sufficient in organism.

PMID- 16792313
TI  - [The tension-free hernioplasty with a polypropylene endoprosthesis "Esfil" in
      patients with incarcerated abdominal hernias of great and giant size].
AB  - In experiments in 24 rabbits it was found that endoprosthesis had no negative
      effects on the course of the wound process and did not prevent elimination of
      infection from the wound. "Esfil" was used for plasty of the abdominal wall in 38
      patients with incarcerated postoperative, umbilical and inguinal hernias of great
      and giant sizes. No patient had rejections of the synthetic material, no
      recurrent hernias during the first year after operation.

PMID- 16792314
TI  - [Clinical peculiarities of diffuse toxic goiter in males].
AB  - A comparative analysis of thyrotoxicosis in 180 males and 121 females has shown
      that during the recent 15 years the number of males operated upon for diffuse
      toxic goiter (DTG) has become 2.6 times greater. Thyrotoxicosis in men is
      characterized by an aggressive course, is followed by cardiac complications,
      ophthalmopathy, impaired sexual function, appearance of foci of malignant growth,
      spread of diffuse hyperplasia of the thyroid gland behind the breast bone and
      trachea. Cessation of thyreostatic therapy resulted in quick recurrence of the
      disease. Repeated courses of treatment with thyreostatics increased the risk of
      irreversibility of changes in the heart muscle, impairment of regenerative
      abilities and massive lymphoid infiltration of the thyroid tissue followed by
      hypothyrosis. Early surgical treatment of men with DTG facilitated a rapid and
      reliable restoration of vitally important functions and recovery of most operated
      men and women.

PMID- 16792315
TI  - [The influence of regional metastases on prognosis in papillary cancer of the
      thyroid gland].
AB  - The author analyses a group of 2917 patients with papillary carcinoma of the
      thyroid gland, on 2210 of them (75.5%) a modified neck dissection was performed,
      268 (9.2%) underwent central lymphodissection, in 449 (15.3%) the lymph nodes
      were not ablated. The signs correlating with the presence of regional metastases
      are discussed. The influence of the tumor size, invasion of the surrounding
      tissues and the presence of regional metastases on the prognosis for life and
      recovery is considered. Advantages of the modified cervical dissection which is
      thought to be the best method for treatment of a local recurrence of papillary
      carcinoma, safe and followed by a minimal number of complications when fulfilled
      by an experienced surgeon are discussed.

PMID- 16792316
TI  - [Clinico-neurological features, diagnostics and surgical treatment of
      posttraumatic chronic subdural hematomas].
AB  - The article presents results of a complex clinico-neurological and radiological
      examination of 47 patients with posttraumatic chronic subdural hematomas.
      Clinical features of the course of chronic hematomas against the background of a
      severe cranio-cerebral injury are established. On the basis of an analysis of
      data of a complex examination and results of the surgical treatment, the
      indications to using different methods of surgery are specified. The optimum
      methods of surgical treatment of patients with chronic subdural hematomas were
      found to be minimally invasive operations.

PMID- 16792317
TI  - [Intravascular morphological manifestations of the syndrome of disseminated
      intravascular coagulation (DIC) in the acute period of burn disease].
AB  - The authors have made an analysis of the frequency and character of intravascular
      microthrombi found in the capillaries and venules of the inner organs on the
      basis of results of 20 autopsies of adult patients with DIC having the burned
      body surface from 25 to 90%. The patients were treated and died in the Russian
      Burn Center. In the 18 dead out of 20 patients different kinds of microthrombi
      were revealed. The greatest number of microthrombi were found in the brain, the
      fewest--in the kidneys.

PMID- 16792318
TI  - [The course of the nearest postoperative period in patients with injuries of the
      spleen].
AB  - The authors have analyzed the course of the postoperative period in 410 patients
      operated on for isolated, combined and multiple traumas with injuries of the
      spleen. The character of the operation (splenectomy, splenectomy with
      autolientransplantation, organ preserving operations) had no significant
      influence on frequency of complications or lethality.

PMID- 16792319
TI  - [Biorhythmic characteristics of patients with total primary and revision hip
      replacement].
AB  - Age-dependent fluctuations of primary total and revision endoprosthesis have been
      found which appear to reflect changes in the activity of the inflammation process
      that can be regarded to be an element of periodic diseases. This seems to depend
      on the regulatory-metabolic shifts caused by aging.

PMID- 16792320
TI  - [Low doses of aprotinin in reducing blood loss and allogenic transfusions in
      operation under conditions of extracorporeal circulation with using cell saver].
AB  - A blind prospective randomized investigation included 109 patients with ischemic
      heart disease undergoing operations of coronary shunting under conditions of
      extracorporeal circulation. It was shown that aprotinin in the dose of 3 ppm KIU
      in operations of coronary shunting under conditions of reserving autoblood,
      extracorporeal circulation and using cell saver facilitates reducing
      postoperative blood loss, but does not lead to less frequent allogenic
      transfusions.

PMID- 16792321
TI  - [Specific features of surgical strategy in gastroduodenal ulcer bleedings in
      elderly and senile patients].
AB  - An analysis of results of surgical treatment of 107 elderly and senile patients
      with gastroduodenal ulcer bleedings was made. Emergency operations were fulfilled
      on 47 patients, urgent operations on 56 patients and planned operations--on 4
      patients. Ulcers of large size prevailed. Most of the patients had complications
      of ulcer disease. Palliative interventions were performed on 27 patients:
      suturing the vessel--in 20, ablation of the ulcer--in 7. Lethality was 33.3%.
      Radical operations were performed on 80 patients: resection of the stomach--in
      75, vagotomy--in 5. Lethality was 16.3%.

PMID- 16792322
TI  - [Radical perineal prostatectomy].
AB  - The authors have compared results of the first 9 perineal prostatectomies to a
      similar group of patients who underwent radical retropubic prostatectomy. In the
      group of patients after perineal prostatectomies the time of operation was at the
      average two hours less and the volume of blood loss was also two times less.
      Perineal radical prostatectomy is an effective modem method of treatment of
      localized prostate cancer. For many patients it will be a valuable alternative of
      the retropubic radical prostatectomy.

PMID- 16792323
TI  - [Stenosing ligamentitis of fingers].
AB  - The authors propose a classification of the disease according to the degree of
      the pathological process. Conservative methods are analyzed and the necessity to
      perform operations at early stages of the disease is substantiated.

PMID- 16792324
TI  - [A unique observation of a congenital diaphragmatic hernia].

PMID- 16792325
TI  - [Total necrosis of the stomach].

PMID- 16792326
TI  - [Operative treatment of mesenchymal hamartoma of the liver].

PMID- 16792327
TI  - [Successful treatment of multiple complicated echinococcosis of the liver].

PMID- 16792328
TI  - [The possibilities of surgical treatment of gangrene of the small intestine in
      thrombosis of mesenterial vessels in a senile woman].

PMID- 16792329
TI  - [Glomangioma of fingers (disease of Barre-Masson)].

PMID- 16792330
TI  - [Critical ischemia of lower extremities. What is to be done? (Apropos of the
      article of A.D. Aslanov et al. "Comparative assessment of chronic critical
      ischemia of lower extremities in elderly and senile patients".--Vestnik
      chirurgii.--2003.--No 4.--P. 83-86 and the article of N.G. Stepanov "Can we
      agree?"--Vestnik chirurgii.--2004.--No 6.--P 87-88)].

PMID- 16792331
TI  - [Cranio-cerebral trauma with a severe clinical course].

PMID- 16792332
TI  - [Methods of electrostimulation of the gastrointestinal tract].

PMID- 16792333
TI  - [Errors in diagnosis of acute appendicitis in children made by surgeons of
      regional hospitals].

PMID- 16792334
TI  - Surveillance of antibiotic resistance in non invasive clinical isolates of
      Streptococcus pneumoniae collected in Belgium during winters 2003 and 2004.
AB  - A total of 391 and 424 non-invasive isolates of Streptococcus pneumoniae
      collected by 15 laboratories during the 2003 and 2004 survey were tested for
      their susceptibility by a microdilution technique following NCCLS
      recommendations. Insusceptibility rates (IR) in the two surveys (2003/2004) were
      as follows: penicillin 15.0/14.7% [8.4/6.4% Resistance (R)], ampicillin
      17.4/14.6% (R 9.0/7.1%), amoxicillin +/- clavulanic acid 2.6/1.2 % (R 0/0%),
      cefaclor 14.3/14.1% (R 11.5/13.4%), cefuroxime 13.6/12.7% (R 10.5/11.8%),
      cefuroxime-axetil 10.5/11.8% (R 10.0/9.2%) (breakpoints based on 250 mg),
      cefotaxime 4.9/6.2% (R 1.3/2.4%), ceftazidime NotTested (NT)/6.4 (R NT/2.6%),
      cefepime NT/6.4 (R NT/2.6%), imipenem 7.7/8.9 % (R 1.8/1.4%), ertapenem 0.8/NT%
      (R O/NT%), ciprofloxacin 13.8/9.0% (R 4.3/2.4%), levofloxacin 3.3/2.8% (R
      1.5/0.2%), moxifloxacin 0.6/0.2% (R 0.3/0%), ofloxacin 13.5/9.0% (R 4.3/2.4%),
      erythromycin 26.1/24.7% (R 25.3/24.5%), azithromycin 25.4/24.7% (R 24.6/24.5%),
      telithromycin 0.8/0.2% (R 0.5/0%), clindamycin 21.2/18.4% (R 19.2/17.7%) and
      tetracycline 32.3/22.1% (R 29.2/19.3%). There were only minor differences in
      resistance rates according to age, sample site, admission type (i.e. ambulatory,
      hospitalized or long-term care facility patients), gender and geographic origin.
      Overall, telithromycin (MIC50, MIC90 in 2003/2004: 0.015 microg/ml, 0.12
      microg/ml/ 0.008,0.06 respectively), ertapenem (0.03; 0.25/NT), moxifloxacin
      (0.06; 0.25/0.06, 0.12), and amoxicillin +/- clavulanic acid (0.03; 0.25/0.015,
      0.5) were the most active compounds in both surveys. In 2003, the most common
      resistance phenotype was isolated insusceptibility to tetracycline (10.5%)
      followed by combined insusceptibility to erythromycin and tetracycline (9.3%).
      Erythromycin-tetracycline resistance (10.4%) was the most common in 2004.
      Isolates showing resistance to an antibiotic were significantly more present in
      2003 than in 2004 (50.4% versus 40.8%). In penicillin-insusceptible isolates,
      MICs of all beta-lactams were increased but cross-resistance between penicillin
      and other beta-lactams in the penicillin-insusceptible isolates was not complete.
      In the 2003 survey, most of these isolates remained fully susceptible to
      ertapenem (94.9%) and amoxicillin +/- clavulanic acid (83.1%). In the 2004
      survey, 91.9% of the penicillin insusceptible isolates remained susceptible to
      amoxicillin +/- clavulanic acid. In both surveys, the most common serotypes in
      penicillin insusceptible isolates were 14, 23,19 and 9 (20.0%, 20.0%, 16.4% and
      10.9% respectively in 2003; 41.6%, 11.7%, 15.0% and 18.3% respectively in 2004).

PMID- 16792335
TI  - Implementation of antibiotic management teams in Belgian hospitals.
AB  - In 2002-03, the Belgian government subsidized in part the activities of local
      Antibiotic Managers (AMs) in 36 hospitals selected based on the presence of an
      operational multidisciplinary Antibiotic Management Team (AMT). AMs were trained
      as Internists (28), Microbiologists (13) and Hospital Pharmacists (13). The
      hospitals were representative of Belgian hospitals in affiliation, regional
      origin and size. The financing scheme allowed the implementation of 175
      antibiotic management interventions, with a mean of 5 interventions/hospital. The
      activities reported in the first 9-month progress reports were analyzed according
      to national guidelines for AMTs. All hospitals irrespective of size or
      affiliation had undertaken a wide range of measures: review of formulary (29),
      implementation of new clinical guidelines (24), restricted access to selected
      antibiotics (25), improvement of antibiotic susceptibility testing methods (12),
      development of antibiotic consumption database (35) and analysis of antibacterial
      susceptibility data (31). Advertisement type categorization of communication
      methods showed that education of prescribers was based on multimodal
      communication. All hospitals used at least one passive method, 39% at least one
      active method and 55% at least one personalized method. The quality of
      communication was higher in hospitals with teaching affiliation. In conclusion,
      hospitals that received a financial incentive under theAMT pilot phase have
      developed multimodal antibiotic policy interventions independently of the
      hospital size and teaching status. Extension to all Belgian hospitals appears
      warranted. The impact of AMTs and AMs on the quality of use of antibiotics and
      trends of antibiotic resistance and cost will be monitored based on standardized
      indicators.

PMID- 16792336
TI  - In which patients will performing an oral glucose tolerance test yield the
      highest rate of positive results?
AB  - AIM: To determine a valid numerical score according to the present risk factors
      for the prediction of impaired glucose tolerance in our patients. MATERIALS AND
      METHODS: A total of 502 cases (340 females, 162 males; mean age: 48.3 +/- 10.3)
      without overt diabetes aged over 20, whose fasting plasma glucose level were
      below 126 mg/dl were included in this study. After fasting blood samples were
      drawn, a 2-h oral glucose tolerance test was performed. Bivariate and
      multivariate analyses were performed to obtain a numerical score for predicting
      impaired glucose tolerance using risk factors such as age, sex, positive family
      history for diabetes, body mass index, waist circumference, blood pressure,
      triglycerides, HDL cholesterol, and fasting plasma glucose. RESULTS: According to
      the 2-h plasma glucose levels, impaired glucose tolerance was detected in 96 of
      the patients, and diabetes was detected in 5 patients, while the remaining 401
      patients had normal glycaemic values. Age (> or = 50), hypertension, high
      triglycerides, large waist, body mass index > or = 25 kg/m2, and a fasting plasma
      glucose level of 100-109 mg/dl, or 110-125 mg/dl were associated with an impaired
      glucose tolerance (p<0.05). In a 8-point scale formed using these 6 parameters, a
      score of > or = 6 could predict impaired glucose tolerance with a specificity of
      99% and positive predictive value of 63%. CONCLUSION: A numerical score that
      could be used to predict impaired glucose tolerance in our patients has been
      proposed with this study.

PMID- 16792337
TI  - Hypothyroidism has no impact on insulin sensitivity assessed with HOMA-IR in
      totally thyroidectomized patients.
AB  - The influence of thyroid hormones on insulin and glucose metabolism is
      controversial. We examined the impact of hypothyroidism on insulin sensitivity in
      22 hypothyroid patients (15 females and 7 males, mean age 51.0 +/- 12.36 yrs).
      All subjects had a history of total thyroidectomy and radioiodine ablation for
      differentiated thyroid cancer. Each subject ceased levothyroxine treatment six
      weeks prior to admission. The controls were 17 healthy individuals, 6 women and
      11 men, mean age 55.12 +/- 14.17 years. TSH, free thyroxine, and the HOMA index
      of insulin sensitivity, as well as HOMA B (%) and HOMA S (%) were assessed.
      Insulin sensitivity was compared between the groups, and the correlation between
      FT4 and TSH and insulin sensitivity was calculated. RESULTS: The mean FT4 was 4.6
      +/- 4.64 pmol/L in the examined group vs. 16.2 +/- 1.8 pmol/L in controls, p<005;
      TSH 72.11 +/- 36.73 pmol/L vs. 1.24 +/- 1.07 pmol/L, p<0.005; plasma glucose 4.68
      +/- 0.47 mmol/L vs. 5.04 +/- 0.62mmol/L, p=0.0436; plasma insulin 8.07 +/- 9.39
      microU/mL vs. 7.24 +/- 4.06 microU/mL, p=0.7877; HOMA index 1.79 +/- 2.53 vs.
      1.69 +/- 1.09, p=0.5148; HOMA B (%) 102.46 +/- 41.59 vs. 85.95 +/- 26.87,
      p=0.1926, and HOMA S (%) 150.46 +/- 95.90 vs. 153.80 +/- 108.85, p= 0.6710, in
      subjects and controls, respectively. The levels of insulin sensitivity did not
      differ significantly between the two groups. FT4 and TSH did not influence the
      insulin sensitivity in either group, the correlation was insignificant,
      respectively p=0.5426 and p=0.8175 in the examined group, and p=0.172 and
      p=0.4509 in the controls. CONCLUSION: Hypothyroidism has no impact on insulin
      sensitivity in the examined group.

PMID- 16792338
TI  - The ethical debate on present day paternity testing practices.
AB  - The last years, the number of paternity tests on buccal swabs sold over the
      internet as "test kits", has steeply increased. The commercial providers of these
      services facilitate controversial practices, including clandestine sampling at
      home, anonymous sending off for analysis, motherless testing and using "stolen"
      personal objects containing biological material (combs, cigarette butts). This
      has led to concern on the consequences on the family unit--especially the child-
      which may suffer emotionally, physically and financially. In reaction, legal
      initiatives are appearing throughout Europe. The UK Human Genetics Commission has
      advised that the non-consensual obtaining and analysis of personal genetic
      information should be a new criminal offence. The German Federal Court of Justice
      has ruled that paternity tests performed without the mother's knowledge are
      inadmissible as evidence in lawsuits. French law strictly forbids the application
      of DNA testing without the involvement of the court system. In Belgium, a
      proposal for law has been laid down where the offering to

PMID- 16792339
TI  - Mycobacterium avium complex with a distinct clinical and iconographic
      presentation: the Lady Windermere syndrome.
AB  - Clinically significant pulmonary disease caused by non-tuberculous mycobacteria
      such as Mycobacterium avium Complex (MAC) usually occurs upon pre-existing lung
      diseases or immune-deficiency. In 1992, a particular presentation of pulmonary
      MAC, occuring in otherwise healthy middle-aged women, was described with
      pulmonary consolidations localized in lingula and middle lobe. For this specific,
      rare condition, the term Lady Windermere syndrome was introduced. We report a
      particular case of this syndrome, in which an otherwise healthy individual
      developed clinically significant disease upon MAC (subtype: Mycobacterium avium)
      infection of the right middle lobe and lingula of the lung. The patient did not
      have the classical risk factors for developing this syndrome (e.g. habitual cough
      suppression, long and narrow bronchi) indicating their modest contribution in the
      pathogenesis. In our case, guideline based therapy was found to be inadequate
      because of multi-drug resistance, so an alternative treatment regime was given
      with good clinical result.

PMID- 16792340
TI  - Donor cell leukemia developing after hematopoietic stem cell transplantation for
      multiple myeloma.
AB  - The development of secondary leukemia in donor cells after allogeneic stem cell
      transplantation is a rare event. We describe the occurrence of acute myeloid
      leukemia in donor cells 4 years after a stem cell transplantation for multiple
      myeloma. The multiple myeloma was relapsing at the time of the onset of acute
      myeloid leukemia. Secondary leukemia in donor cells after transplantation for
      multiple myeloma has not yet been reported.

PMID- 16792341
TI  - The dental enterprise: its transition from xenodontic to biodontic dentistry.

PMID- 16792342
TI  - Dentin bond strengths of simplified adhesives: effect of dentin depth.
AB  - The objective of this study was to compare the shear bond strength of 3
      simplified adhesive systems applied on shallow vs deep dentin. For superficial
      dentin, 30 human molars were sectioned with a diamond saw to expose dentin
      immediately below the dentoenamel junction. For deep dentin, 30 molars were
      sectioned 3 mm below the dentoenamel junction. The teeth were mounted, polished
      to 600-grit, and randomly assigned to 3 groups (n=10): Single Bonda and OptiBond
      Solo, total-etch adhesives, and Clearfil Liner Bond 2V, a self-etching primer
      adhesive. Adhesives were applied, the restorative material Filtek Z250 inserted
      in a No. 5 gelatin capsule, and light-cured. After 24 hours in water at 37
      degrees C, shear bond strength was measured with an Instron at 5 mm/min. The data
      were analyzed with 2-way ANOVA and Duncan's post-hoc test. The results showed the
      following shear bond strengths (mean +/- SD in MPa): Single Bond/superficial
      dentin = 22.1 +/- 2.8; Single Bond/deep dentin = 14.2 +/- 7.0; OptiBond
      Solo/superficial dentin = 18.9 +/- 4.1; OptiBond Solo/deep dentin = 18.4 +/- 4.8;
      Clearfil Liner Bond 2V/superficial dentin = 21.0 +/- 7.4; Clearfil Liner Bond
      2V/deep dentin = 17.6 +/- 5.9. There were no significant differences between mean
      shear bond strength for the factor "adhesive system" (P>.822). The Duncan's test
      showed that Single Bond resulted in higher shear bond strength on superficial
      dentin than on deep dentin. The mean shear bond strength for Clearfil Liner Bond
      2V and OptiBond Solo were not influenced by dentin depth. When data were pooled
      for dentin depth, deep dentin resulted in statistically lower bond strengths than
      superficial dentin (P<.01). The influence of dentin depth on shear bond strength
      depends on the specific composition of the dentin adhesive.

PMID- 16792343
TI  - Using cavity liners with direct posterior composite restorations.
AB  - Cavity liners have traditionally been used in direct and indirect restorations
      for purposes such as promoting reparative dentin and neutralizing acids. Today,
      liners are used when resin composites are used as the restorative materials on
      the posterior teeth, but for a different reason. Clinically, liners are
      considered to decrease sensitivity and wet the cavity better than restorative
      composites because of their flowability, adaptation to the dentinal surface, and
      adhesion. As bonding systems and composite materials continue to improve and
      become better understood, so do the techniques for placing composites. This has
      led to the reassessment of the clinical relevance and function of liners. Some
      clinicians don't use cavity liners, assuming they are a thing of the past; some
      use composite liners, and others use resin-modified glass ionomer liners.
      Additionally, there is not a clear agreement over the function of liners, such as
      when and why they should be used or what type of liner material would provide the
      best performance for a particular clinical situation. This article attempts to
      clarify some of the confusion surrounding the use of liners by reviewing the
      available literature on the subject and attempting to give evidence-based
      rationale for the use and protocol for the clinician.

PMID- 16792344
TI  - The effect of EDTA in attachment gain and root coverage.
AB  - Root surface biomodification using low pH agents such as citric acid and
      tetracycline has been proposed to enhance root coverage following connective
      tissue grafting. The authors hypothesized that root conditioning with neutral pH
      edetic acid would improve vertical recession depth, root surface coverage, pocket
      depth, and clinical attachment levels. Twenty teeth in 10 patients with Miller
      class I and II recession were treated with connective tissue grafting. The
      experimental sites received 24% edetic acid in sterile distilled water applied to
      the root surface for 2 minutes before grafting. Controls were pretreated with
      only sterile distilled water. Measurements were evaluated before surgery and 6
      months after surgery. Analysis of variance was used to determine differences
      between experimental and control groups. We found significant postoperative
      improvements in vertical recession depth, root surface coverage, and clinical
      attachment levels in test and control groups, compared to postoperative data.
      Pocket depth differences were not significant (P<.01).

PMID- 16792345
TI  - Experimental chairside test for the rapid diagnosis of oropharyngeal candidiasis.
AB  - Oral infection with Candida fungal species is very common. Oral candidiasis is
      usually diagnosed by clinical appearance because no chairside diagnostic methods
      are available. In contrast, a rapid latex agglutination (RLA) test has proven
      useful for in-office diagnosis of vulvovaginal candidiasis. This study was
      undertaken to determine if the RLA technique might be used to provide a quick
      chairside test for oral candidiasis. Twenty-five patients participated in the
      study, including 21 patients with clinical evidence suggestive of oral
      candidiasis serving as the experimental group and 4 patients with apparent good
      oral health serving as controls. The presence of oral candidiasis was evaluated
      using RLA, fungal culturing, and cytology. RLA testing was consistent with
      established diagnostic tests in patients with oral candidiasis. However, RLA
      false positive results were noted, and the test is highly technique-sensitive and
      subjective. The technique is worthy of further study to determine its ultimate
      value in the diagnosis of oral candidiasis.

PMID- 16792346
TI  - Sales representatives: the untapped educational resource.

PMID- 16792347
TI  - Review of the arc process modeling for fullerene and nanotube production.
AB  - The arc process remains the easiest and cheapest technique to obtain significant
      quantities of single wall carbon nanotubes (SWCNTs) with excellent structural
      properties. These nanotubes are quite straight and present few topological
      defects. However, the major inconvenience of this process remains the difficult
      in situ control of the final material's purity and physical properties. The first
      NASA/Rice workshop on growth mechanisms was devoted to addressing some specific
      questions on how and where the nanotubes are formed in several processes
      including the arc. Further advancement requires a detailed understanding of the
      growth mechanisms of fullerene, nanotubes and soot and their connection with
      process parameters. This approach is not highly developed today because of the
      coupling made by non-equilibrium plasma with the nonlinear chemical system makes,
      in which rate coefficients and reactions are not well known and this makes
      modeling difficult. This article is an attempt to analyze the effect of the
      individual arc parameters yielding guidelines for building a mechanistic
      understanding of carbon based nanomaterial growth in the arc discharge.

PMID- 16792348
TI  - Atomistic simulations of catalyzed carbon nanotube growth.
AB  - We review the advances made in understanding the mechanism of catalyzed carbon
      nanotube growth, with the main focus on direct dynamics and molecular dynamics
      studies of single-walled carbon nanotube (SWNT) growth. These studies have
      deepened our understanding of the catalytic SWNT nucleation and growth
      mechanisms, but more accurate and efficient methods are required for a complete
      investigation at experimental growth conditions.

PMID- 16792349
TI  - Recent advances in laser synthesis of single-walled carbon nanotubes.
AB  - Very shortly following the discovery of single-walled carbon nanotubes laser
      based methods emerged as reliable ways to produce moderate quantities with very
      consistent composition and properties. They have also proven to be good platforms
      for the systematic investigation of various synthesis parameters in the hope of
      better understanding the growth process. Several variations exist with
      differences such as laser wavelength, number of lasers, background temperature,
      and target composition. A number of common elements have emerged for the
      production of both high quality and high yields of SWNT, such as the
      effectiveness of bimetal catalysts like CoNi and NiY, and the need for high
      process temperatures and controlling the rate of cooling. Combined with the
      growing amount of in situ diagnostic and computational modelling data we are
      slowly making progress towards understanding the growth process. This article
      will present an overview of recent advancements in laser-based synthesis methods
      and what information can be extracted about the growth process.

PMID- 16792350
TI  - Studies on mechanism of single-walled carbon nanotube formation.
AB  - We presented detailed studies of the formation of single-walled carbon nanotubes
      by an aerosol method based on the introduction of pre-formed catalyst particles
      into conditions leading to carbon nanotube synthesis. Carbon monoxide and iron
      nanoparticles were used as a carbon source and a catalyst, respectively. The
      vital role of etching agents such as CO2 and H2O in CNT formation was
      demonstrated on the basis of on-line Fourier-transform infrared spectroscopy
      measurements. Hydrogen was shown to participate in the reaction of carbon release
      and to prevent the oxidation of the catalyst particles and the hot wire. The
      addition of H2 and small amounts of CO2 and H2O led to an increase in the carbon
      nanotube lengths. The catalyst particle evaporation process inside the reactor
      was found to become significant at temperatures higher than 1100 degrees C. The
      carbon nanotube growth was found to occur at a temperature of around 900 degrees
      C in the heating section of the reactor by in situ sampling and the growth rate
      was calculated to exceed 1.1 microm/s. A detailed analysis of possible processes
      during carbon nanotube formation revealed heptagon transformation as a limiting
      stage. A mechanism for carbon nanotube formation was proposed.

PMID- 16792351
TI  - Role of the catalyst in the growth of single-wall carbon nanotubes.
AB  - Classical molecular dynamics simulations are carried out to analyze the physical
      state of the catalyst, and the growth of single-wall carbon nanotubes under
      typical temperature and pressure conditions of their experimental synthesis,
      emphasizing the role of the catalyst/substrate interactions. It is found that a
      strong cluster/substrate interaction increases the cluster melting point,
      modifying the initial stages of carbon dissolution and precipitation on the
      cluster surface. Experiments performed on model Co-Mo catalysts clearly
      illustrate the existence of an initial period where the catalyst is formed and no
      nanotube growth is observed. To quantify the nature of the Co-Mo2C interaction,
      quantum density functional theory is applied to characterize structural and
      energetic features of small Co clusters deposited on a (001) Mo2C surface,
      revealing a strong attachment of Co-clusters to the Mo2C surface, which may
      increase the melting point of the cluster and prevent cluster sintering.

PMID- 16792352
TI  - Fe/C interactions during SWNT growth with C2 feedstock molecules: A quantum
      chemical molecular dynamics study.
AB  - We are presenting the first quantum chemical molecular dynamics (QM/MD) model
      simulations for iron catalyzed single-walled carbon nanotube (SWNT) growth based
      on the density functional tight binding (DFTB) quantum chemical potential. As
      model systems, open-ended (10,10) armchair tube fragments were selected with 0,
      10, and 20 Fe atoms attached in 1,4-positions on the open rims, and ensembles of
      randomly oriented C2 molecules were included to simulate carbon plasma feedstock
      molecules. Isokinetic trajectories at 1500 K to 3000 K show that divalent Fe
      increases the number of coordination partners with carbon and/or Fe, depending on
      the Fe concentration. Fe/C interactions weaken the tube sidewall due to electron
      transfer from Fe into antibonding carbon orbitals, and C2 addition occurs mainly
      in an Fe-C2-Fe bridge addition mechanism, while growth of polyyne chains
      characteristic for high-temperature carbon systems is suppressed in the presence
      of Fe on the rims of the growing SWNT. Our findings are the first quantum
      chemical evidence for the importance of intermetallic interactions during SWNT
      growth.

PMID- 16792353
TI  - Combined thermal and gas dynamics numerical model for laser ablation of carbon.
AB  - One of the major methods of production of carbon nanotubes is the laser ablation
      process. In this process, a powerful nanosecond-scale laser beam illuminates a
      target. The resulting explosion produces a plume of rapidly expanding gaseous
      carbon with embedded metallic catalysts, on whose surfaces the nanotubes are
      formed. The time-scale of a single laser pulse is of the order of nanoseconds
      whereas the plume development and growth of nanotubes take up to several
      milliseconds. The synthesis process largely depends on the plume properties,
      i.e., on the temperature, pressure, and density of the expanding plume. In turn,
      the plume propagation depends on the ablation speed, pressure, and density. In
      the current study, a combined thermal and gas dynamics model is proposed,
      implemented and tested. The proposed model is based on combined conduction heat
      transfer within the solid target, carbon sublimation process described by
      equilibrium thermodynamics, and process of plume development described by
      continuous gas dynamics. The carbon sublimation model is based on Clausius
      Clapeyron equation and conservation of energy for differential control volume.
      The parameters of the injected plume are defined by this thermal model. The
      validity of viscous and inviscid models of plume dynamics is discussed. The
      ability of finite-volume discretizations to capture the plume dynamics and its
      roll-up is compared for various numerical schemes. To evaluate the accuracy of
      numerical modeling of plume dynamics, we compare finite-volume discretization
      based on Relaxing TVD scheme with that based on the upwind scheme with Roe
      averaging at the cell interface and non-linear ENO scheme for second-order flux
      formulas.

PMID- 16792354
TI  - All-electron DFT modeling of SWCNT growth on iron catalysts from carbon monoxide
      feedstock.
AB  - Electronic and geometrical structures of Fe4Cn(CO)m (n + m < or = 6) and their
      singly negatively and positively charged ions are computed using density
      functional theory with generalized gradient approximation. Isomers with CO bonded
      directly to the cluster iron atoms and bonded to a carbon atom chemisorbed on the
      cluster surface are optimized for the Fe4C2CO, Fe4C2(CO)2, Fe4C3CO, and Fe4C4CO
      series. Optimizations of a large number of differently shaped Fe4C4, Fe4C5, and
      Fe4C6 clusters are performed to find trends in preferable arrangement of carbon
      atoms, in particular, to determine the relative energetics of structures with
      single C atoms versus those with C2 dimers or C3 trimers. The computed total
      energies are used to estimate the energetics of the Boudouard disproportionation
      reactions Fe4Cn(CO)m + 00-->Fe4Cn+1(CO)m-1 + CO2.

PMID- 16792355
TI  - Modelling the nucleation and chirality selection of carbon nanotubes.
AB  - The selection of chiralities of single-walled carbon nanotubes is one of the key
      problems of nanotube science. We suggest that the chirality-selective growth of
      SWNTs could be achieved using chemical vapour deposition (CVD) by controlling the
      type of caps that form during the nucleation stage. As the catalyst can be solid
      during CVD, the formation of particular caps may be favoured by an epitaxial
      relationship to the catalyst surface. The corresponding tubes would then grow
      preferentially. We show by ab-initio calculations that the formation energy of
      some lattice-matched caps and tubes are 1-2 eV lower than the non lattice-matched
      structures.

PMID- 16792356
TI  - Spatial evolutions of Co and Ni atoms during single-walled carbon nanotubes
      formation: measurements and modeling.
AB  - Spatial investigations of nickel and cobalt atoms and of C2 and C3 radicals are
      performed by laser induced fluorescence (LIF) in a continuous CO2 laser
      vaporization reactor during the synthesis of single-walled carbon nanotubes. The
      chemical composition of the gas vaporized from bimetallic Ni/Co catalysts-carbon
      targets is determined using a chemical kinetic model. In this model, the
      evolution of Ni and Co atoms is driven by kinetics of condensation/evaporation
      process of pure metal clusters. Metal-carbon clusters are assumed to form from
      soot particles (C80) and 128-atom metal clusters. Spatial profiles of Ni and Co
      atoms obtained by LIF are compared with the calculations to validate the modeling
      and to adjust the input data. The value of the initial molar fraction of carbon
      metal mixture diluted in helium is determined through a parametric study. Good
      agreement is found between the measured and the calculated evolution of Ni for a
      molar fraction of the helium diluent ranging from 10 to 15%. To fit the spatial
      profile of Co, the activation energy is adjusted in the evaporation rate,
      changing the cobalt dimer bond energy. The latter is found to be largely
      uncertain; and three values are tested: 167, 208, and 230 kJ x mol(-1). From
      comparison, the activation energy is found to be 208 kJ x mol(-1). However, the
      C2 LIF profiles show that the depletion of C2 is accelerated when cobalt is
      present. The observed Co evolutions suggest that small Co-C clusters are easier
      and/or faster to form compared to Ni-C clusters.

PMID- 16792357
TI  - Modeling of the anodic arc discharge and conditions for single-wall carbon
      nanotube growth.
AB  - A model of the arc discharge used for a single wall carbon nanotube (SWNT)
      synthesis is developed. Coupling solution of the non-equilibrium, Knudsen layer,
      with hydrodynamic layer and discharge column provides self-consistent solution
      for the ablation rate and plasma parameter distribution. It is predicted that the
      interelectrode gap decreases with the background pressure increase. Conditions
      for single wall carbon nanotube formation in the arc discharge method of nanotube
      synthesis are described. Carbon nanotube seed formation and charging in the
      interelectrode gap are found to be very important effects that may alter carbon
      nanotube formation in the cathode region. This model predicts that the long
      carbon nanotubes in the high pressure Helium environment can be deposited on the
      cathode surface. Model predictions are found to be in agreement with experiment.

PMID- 16792358
TI  - Dispersion of carbon nanotubes using organic solvents.
AB  - Phenyl ethyl alcohol was used for fast and stable dispersion of carbon nanotubes.
      This solvent, more effective than ethanol and toluene, allows easy dispersion of
      carbon nanotubes for TEM characterization. For TEM grids prepared at high
      dilution, it is possible to observe each tube separately. Applying that solvent,
      it was possible to measure the length, the diameter and the solubility of
      different carbon nanotubes samples.

PMID- 16792359
TI  - Formation of SWCnts in arc plasma: effect of graphitization of Fe-doped anode and
      optical emission studies.
AB  - Fe-doped (ca. 1 at%) homogeneous graphite electrodes (with different graphite
      microcrystallites, degree of graphitization and, thereby, electrical
      conductivities) were used to produce single-walled carbon nanotubes (SWCNTs) in
      Ar/Kr/Xe-H2 arc plasma under pressure equal to 26 kPa. The use of electrode with
      the smaller primary particle size (about 5 nm) comparing to the well-graphitized
      electrode (25 nm) drastically increased the yield of SWCNTs in Ar-H2 arc plasma,
      while plasma parameters (temperature, C2 content, and namely carbon vapor
      pressure) remained on similar levels. However, the use of electrodes with larger
      grain size (25 nm) can lead to SWCNTs growth when they are arc ablated under the
      presence of Kr (or Xe)-H2 gas mixture. Thus, the mechanism of CNT formation seems
      to be more complex that the one involving only simple carbon species (e.g., C2).

PMID- 16792360
TI  - Fabrication of crossed junctions of semiconducting and metallic carbon nanotubes:
      a CNT-gated CNT-FET.
AB  - We have developed a method to fabricate crossed junctions between semiconducting
      (s) and metallic (m) carbon nanotubes (CNTs) combining electric field directed
      chemical vapor deposition growth and dielectrophoretic alignment. By separating
      the s- and m-CNTs with a thin dielectric an ultra-small field effect transistor
      (FET) was fabricated. By using the m-CNT as a gate it was possible to modulate
      the source-drain current through the s-CNT FET channel. We have also used the m
      CNT as an electrical lead. An off-state current lowering was observed when the m
      CNT lead was used as a drain electrode.

PMID- 16792361
TI  - A nucleation and growth model of vertically-oriented carbon nanofibers or
      nanotubes by plasma-enhanced catalytic chemical vapor deposition.
AB  - Carbon nanofibers are grown by direct current and hot filaments-activated
      catalytic chemical vapor deposition while varying the power of the hot filaments.
      Observations of these carbon nanofibers vertically oriented on a SiO2 (8 nm
      thick)/Si(100) substrate covered with Co nanoparticles (10-15 nm particle size)
      by Scanning Electron and Transmission Electron Microscopies show the presence of
      a graphitic "nest" either on the surface of the substrate or at the end of the
      specific nanofiber that does not encapsulate the catalytic particle. Strictly in
      our conditions, the activation by hot filaments is required to grow nanofibers
      with a C2H2 - H2 gas mixture, as large amounts of amorphous carbon cover the
      surface of the substrate without using hot filaments. From these observations as
      well as data of the literature, it is proposed that the nucleation of carbon
      nanofibers occurs through a complex process involving several steps: carbon
      concentration gradient starting from the catalytic carbon decomposition and
      diffusion from the surface of the catalytic nanoparticles exposed to the
      activated gas and promoted by energetic ionic species of the gas phase;
      subsequent graphitic condensation of a "nest" at the interface of the Co particle
      and substrate. The large concentration of highly reactive hydrogen radicals
      mainly provided by activation with hot filaments precludes further spreading out
      of this interfacial carbon nest over the entire surface of the substrate and thus
      selectively orientates the growth towards the condensation of graphene over
      facets that are perpendicular to the surface. Carbon nanofibers can then be grown
      within the well-known Vapor-Liquid-Solid process. Thus the effect of energetic
      ions and highly reactive neutrals like atomic hydrogen in the preferential
      etching of carbon on the edge of graphene shells and on the broadening of the
      carbon nanofiber is underlined.

PMID- 16792362
TI  - The effect of sulfur on the structure of carbon nanotubes produced by a floating
      catalyst method.
AB  - The effect of sulfur on the structures (shell number and diameter distribution)
      of carbon nanotubes (CNTs) was investigated in detail using high resolution
      transmission electronic microscopy (HRTEM) and Raman spectroscopy. Single-walled
      (SWNTs), double-walled (DWNTs), and multi-walled carbon nanotubes (MWNTs) with
      different diameter distributions were obtained only by increasing the sulfur
      addition amount with methane as carbon source. A similar structure change was
      found for ethanol as carbon source with changing the sulfur addition amount.
      These results indicate that addition of sulfur is necessary to enhance the growth
      of SWNTs and DWNTs, independent of the carbon source for our method. Based on the
      growth parameter study, HRTEM observations and kinetic considerations, the role
      of sulfur in the nucleation and growth of CNTs was discussed.

PMID- 16792363
TI  - Fabrication of small diameter few-walled carbon nanotubes with enhanced field
      emission property.
AB  - A unique type of carbon nanotubes with 2 to 5 layers of sidewalls and diameters
      less than 10 nm was synthesized by the thermal chemical vapor deposition (CVD)
      method with MgO supported Fe/Mo catalyst. Unlike the typical CVD grown multi
      walled carbon nanotubes, these few-walled carbon nanotubes (FWNTs) have a high
      degree of structural perfection. They have enhanced electron field emission
      characteristics compared to the current commercial nanotubes, with a low
      threshold field for emission and improved emission stability.

PMID- 16792364
TI  - Electron beam induced structural transformations of SWNTs and DWNTs grown on
      Si3N4/Si substrates.
AB  - Electron beam induced structural transformations are investigated in single-wall
      carbon nanotubes (SWNTs), double-wall carbon nanotubes (DWNTs) and crossed
      nanotube junctions. The nanotubes studied here are synthesized by the chemical
      vapor deposition method. The response of the nanotubes to an electron beam is
      found to be influenced by the presence of coatings of amorphous carbon, graphene
      fragments and structural defects on the tube surface. The dependence of
      structural modifications on electron beam irradiation dose is measured. While
      nanotubes with amorphous carbon, graphene fragment coverage and/or defects
      undergo rapid transformation leading to structure disintegration, those without
      such coverage or defects are more resistant to beam damage. In addition, it is
      shown that the amorphous carbon coverage on the double-wall nanotubes can be
      transformed into graphene layers during electron beam irradiation of coated
      nanotubes. Finally, the relative stability of nanotube side-wall and end-walls
      are investigated through sub-threshold energy and above threshold energy
      irradiation of a model system, C60-filled nanotubes (Peapods). The data indicates
      that electron beams could be used to join nanotubes end-to-end without damaging
      the side-walls.

PMID- 16792365
TI  - The interaction and toxicity of multi-walled carbon nanotubes with Stylonychia
      mytilus.
AB  - The interaction of multi-walled carbon nanotubes (MWNTs) with living unicellular
      protozoan Stylonychia mytilus was studied. The results indicated that MWNTs were
      ingested largely by Stylonychia mytilus. Distribution of MWNTs in the cells,
      redistribution during dividing process of the cells, and excretion from the cells
      were observed successfully with optical microscope. The dependence of viability
      of Stylonychia mytilus was determined on the concentration of MWNTs, ranging from
      0.1 microg/ml to 200 microg/ml. It was found that exposure of Stylonychia mytilus
      to the MWNTs with concentration higher than 1.0 microg/ml induced a dose
      dependent growth inhibition to the cells and the damage occurred, by fluorescence
      microscopy, on the macronucleus and external membrane of the cells. The
      ultrastructure change by electron microscope revealed that the MWNTs exclusively
      localized to the mitochondria of the cells. It was proposed that the damage of
      macronucleus, micronucleus, and membrane of the cells, as well as growth
      inhibition of the cells might be a result of the damage of mitochondria,
      following this exclusive localization. Our finding provides important information
      on the bio-security of MWNTs and their migration in aqueous environment.

PMID- 16792366
TI  - Biocompatibility of native and functionalized single-walled carbon nanotubes for
      neuronal interface.
AB  - Single-walled carbon nanotubes (SWNTs) have unique mechanical, electrical, and
      optical properties and can be easily chemically modified; features that make them
      excellent candidate materials for applications as sensors and stimulators in
      neuronal tissue engineering. The purpose of this study was to demonstrate that
      SWNTs can support neuronal attachment and growth, that simple chemical
      modifications can be employed to control cell growth, that SWNTs do not interfere
      with ongoing neuronal function, and that neurons can be electrically coupled to
      SWNTs. Growth and attachment of the neuroblastoma*glioma NG108, a model neuronal
      cell, was assessed on unmodified SWNT substrates or substrates from SWNTs
      modified with 4-benzoic acid or 4-tert-butylphenyl functional groups using a
      simple functionalization method. SWNT films support cell growth, but at a reduced
      level compared to tissue culture-treated polystyrene. The order of viability and
      cell attachment was tissue culture treated polystyrene > SWNTs > 4-tert
      butylphenyl-functionalized SWNTs > 4-benzoic acid-functionalized SWNTs. Decreased
      cell growth after culture on untreated (non adherent) polystyrene suggested that
      cell attachment was a critical determinant of proliferation and cell growth on
      SWNTs. Fluorescence and scanning electron microscopy revealed decreased neurite
      outgrowth in NG108 grown on SWNT substrates. We are also among the first groups
      to demonstrate electrical coupling of SWNTs and neurons by demonstrating that
      NG108 and rat primary peripheral neurons showed robust voltage-activated currents
      when electrically stimulated through transparent, conductive SWNT films. Our data
      suggest that SWNTs are flexible resource materials for tissue engineering
      application involving electrically excitable tissues such as muscles and nerves.

PMID- 16792367
TI  - Surface modification by electric discharge implemented with electrodes composed
      of carbon nanotubes.
AB  - In this work the electric discharge machining (EDM) implementing with multi-wall
      carbon nanotubes (MWCNT) as a miniscule electrode for pursuing precise surface
      modification was studied. The excellent upright growth of carbon nanotubes on
      copper based alloy substrates by a radio frequency (RF) assisted hot filament
      chemical vapor deposition (HFCVD) method suggests us to exploit MWCNTs as the
      miniature electrodes for discharge machining. The results reveal that the
      electrodes are much endurable to be distorted even when the spoiling rates for
      the polishing of n-type Si wafer (of 10 to approximately 100 omega-cm) are up to
      30 nm/min with. It is expected that MWCNTs can be applied to non-conventional
      material processing especially in miniature discharge machining.

PMID- 16792368
TI  - Synthesis and characterization of supramolecular nanostructures of carbon
      nanotubes and ruthenium-complex Luminophores.
AB  - We constructed and characterized supramolecular nanostructures consisting of
      ruthenium-complex luminophores, which were directly grafted onto short oxidized
      single-walled carbon nanotubes or physically entrapped in silica nanobeads, which
      had been covalently linked to short oxidized single-walled carbon nanotubes or
      hydrophobically adsorbed onto full-length multi-walled carbon nanotubes. These
      structures were evaluated as potential electron-acceptor complexes for use in the
      fabrication of photovoltaic devices, and for their properties as fluorescent
      nanocomposites for use in biosensors or nanoelectronics.

PMID- 16792369
TI  - Electrochemical organization of monolayer protected gold nanoclusters on single
      walled carbon nanotubes: significantly enhanced double layer capacitance.
AB  - This paper reports a novel electrochemical route for anchoring monolayer
      protected gold nanoclusters (size 8 +/- 0.2 nm) on single-walled carbon nanotube
      bundles, resulting in the formation of hybrid materials. Monolayer protected gold
      nanoclusters prepared by modified Brust synthesis route were organized on SWNT
      bundles by cycling the potential in dichloromethane between -1 to +1 V at a scan
      rate of 50 mV/s. Monolayer protected nanoclusters in electrolyte solutions
      possess ionic space charge around them (double layer charging), making them
      suitable for organization on nanotube bundles, by tuning the electrostatic
      interactions. More significantly, analysis of the double layer capacitance of
      these hybrid materials shows almost ten times increase in capacitance compared to
      that of bare SWNT bundles. We believe that these hybrid materials are potentially
      useful in nanoelectronics.

PMID- 16792370
TI  - Fabrication of high quality carbon nanotubes with a simple ethanol-assisted arc
      discharge process.
AB  - In this paper, a simplified ethanol-assisted arc discharge method was developed
      for the fabrication of multi-wall carbon nanotubes in high quality. Carbon
      nanotubes with high purity (80-90%) were obtained through controlling the current
      (15-25 V, 10-25 A) and ethanol concentration (70-100%). The products were
      characterized using transmission electron microscopy (TEM), high-resolution
      transmission electron microscopy (HRTEM), and Raman spectrometry.

PMID- 16792371
TI  - Thermal stability of poly(o-methoxyaniline) layer-by-layer films investigated by
      neutron reflectivity and UV-VIS spectroscopy.
AB  - Neutron reflectivity measurements were used to investigate the thermal stability
      of layer-by-layer (LBL) films of poly(o-methoxyaniline) (POMA), which was probed
      by increasing the temperature up to 80 degrees C of a D2O solution in contact
      with the LBL films. The study was made possible by adsorbing POMA layers on a
      PEI/(PSS/PAH)5/PSS LBL film template, leading to less rough POMA layers in
      comparison with the POMA/poly(vinylsulfonic acid sodium salt) (PVS) LBL films
      adsorbed directly on glass and silicon substrates. While the latter yielded
      almost fringeless neutron reflectivity curves due to the large roughness, the
      fitting of the data for POMA films adsorbed onto the template film and UV-vis
      measurements indicated that the topmost layer is affected for films heated in
      solution up to 80 degrees C. This is essentially the same thermal stability of
      LBL films from the template films made with conventional polyelectrolytes. A
      decrease in thickness of approximately 10 A was inferred when the solution
      temperature increased from 25 degrees C to 80 degrees C, which was maintained
      when the sample was cooled back to 25 degrees C. This decrease, observed for
      solutions of pH 3 and pH 8, is consistent with thermally-stimulated desorption
      and was corroborated by UV-VIS absorption experiments. The unexpected stability
      of the POMA layer at pH 8 is attributed to the layer-by-layer structure of the
      films that allows POMA to remain doped, in its salt emeraldine form, even at high
      pH.

PMID- 16792372
TI  - Synthesis of colloidal gold nanoparticles of different morphologies in the
      presence of triblock polymer micelles.
AB  - The Au nanoparticles have been synthesized in the presence of micellar solutions
      of fixed concentration (i.e. 1.4 x 10(-3) mol dm(-3)) of each poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide), triblock polymers (TBP), such
      as P103, P84, P123, and F127. The nanoparticles have also been synthesized in the
      presence of mixed micellar solutions of binary TBP mixtures such as P103+ P84 and
      P103+P123. In the previous case, "raspberry type" Au nanoparticle-TBP aggregates
      have been observed in which nanoparticles of 2-3 nm have been uniformly
      distributed throughout the TBP micelle. On the other hand, in the latter case,
      apart from such aggregates, prominent ordered morphologies of nanoparticles such
      as rod, sphere, triangle, and hexagonal have also been observed with much larger
      dimensions. This has been attributed to the nucleation process occurring in the
      mixed micelles rather than in the micelles of single TBP components.

PMID- 16792373
TI  - Morphology and surface plasma changes of Au-Pt bimetallic nanoparticles.
AB  - In this study, we examined the amount-dependent change in morphology in a series
      of Au-Pt bimetallic nanoparticles synthesized using chemical reduction. The
      amount of Au precursor was kept constant throughout the experiment. The Au/Pt
      molar ratio was varied from 1/1 to 1/4 to synthesize Pt shell layers with
      different thicknesses. We observed a remarkable shift of the surface plasmon band
      at around 410 nm. By high-resolution transmission electron microscopy (HRTEM) and
      energy-dispersive spectrometry (EDS), the composition of the shell layer was
      found to be Pt-enriched Au-Pt alloy. As the concentration of Pt increases, Pt
      clusters (ca. 1.8 nm in diameter) form a string-like shape on the surface of
      nanoparticles.

PMID- 16792374
TI  - Sol-gel fabrication and photoluminescence properties of SiO2 @ Gd2O3:Eu3+ core
      shell particles.
AB  - A uniform nanolayer of europium-doped Gd2O3 was coated on the surface of
      preformed submicron silica spheres by a Pechini sol-gel process. The resulted
      SiO2 @ Gd2O3:Eu3+ core-shell structured phosphors were characterized by X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field
      emission scanning electron microscopy (FESEM), transmission electron microscopy
      (TEM), photoluminescence (PL) spectra as well as kinetic decays. The XRD results
      show that the Gd2O3:Eu3+ layers start to crystallize on the SiO2 spheres after
      annealing at 400 degrees C and the crystallinity increases with raising the
      annealing temperature. The core-shell phosphors possess perfect spherical shape
      with narrow size distribution (average size: 640 nm) and non-agglomeration. The
      thickness of the Gd2O3:Eu3+ shells on the SiO2 cores can be adjusted by changing
      the deposition cycles (70 nm for three deposition cycles). Under short UV
      excitation, the obtained SiO2@Gd2O3:Eu3+ particles show a strong red emission
      with 5D0-7F2 (610 nm) of Eu3+ as the most prominent group. The PL intensity of
      Eu3+ increases with increasing the annealing temperature and the number of
      coating cycles.

PMID- 16792375
TI  - Assembled CuO hollow spheres from nanoparticles.
AB  - CuO microspheres with hollow interiors were synthesized by a simple method using
      urea as an important reagent to generate soft-template. X-ray diffraction
      pattern, Infrared spectrum, electronic diffraction, field emission scanning
      electron microscopy images, transmission electron microscopy images and high
      resolution transmission electron microscopy investigated the phase structures and
      morphologies of CuO microspheres. The hollow spheres may be formed through the
      assembling of nanoparticles with the assistance of gas bubbles and a self
      generated template and aggregation process was proposed for the formation
      mechanism of the CuO spheres.

PMID- 16792376
TI  - Giant dielectric constant in titania nanoparticles embedded in conducting polymer
      matrix.
AB  - Complex impedance and dielectric permittivity of titania-polypyrrole
      nanocomposites have been investigated as a function of frequency and temperature
      at different compositions. A very large dielectric constant of about 13,000 at
      room temperature has been observed. The colossal dielectric constant is mainly
      dominated by interfacial polarization due to Maxwell-Wagner relaxation effect.
      Two completely separate groups of dielectric relaxation have been observed. The
      low frequency dielectric relaxation arises from surface defect states of titania
      nanoparticles. The broad peak at high frequency region is attributed to Maxwell
      Wagner type polarization originating from the inhomogeneous property of
      nanocomposite. An abrupt change in grain boundary conductivity and dielectric
      relaxation associated with titania was observed at around 150 K. Anomalous
      behavior in conductivity and dielectric relaxation is qualitatively explained by
      band tail structure of titania nanoparticle.

PMID- 16792377
TI  - From sheets to fibers: A novel approach to gamma-AlOOH and gamma-A12O3 1D
      nanostructures.
AB  - The gamma-AIOOH (boehmite) nanofiber bundles have been synthesized via a
      convenient quencher method. Most nanofibers contain even smaller nanowires with
      an average diameter of 5 nm. A series of contrast experiments reveal that the
      evolvement from nanosheets to nanofibers occurs in the quencher process. gamma
      Al2O3 nanofiber bundles with mesoporous character can be obtained by calcining
      relevant gamma-AlOOH nanostructures at 500 degrees C.

PMID- 16792378
TI  - A study of nano-mechanical properties and nano-scratch behavior of boron
      carbonitride films.
AB  - Boron carbonitride (BCN) films were deposited by d.c. unbalanced magnetron
      sputter deposition where a substrate bias ranging from -50 V to -300 V was
      applied to the sample. X-ray photoelectron spectroscopy and Fourier transform
      infrared spectroscopy were used to confirm the composition and bonding structure
      of the BCN films. Surface morphology and roughness were analyzed by atomic force
      microscopy. The nano-mechanical properties and nano-scratch behavior of the
      prepared films were determined by a nano-indentation system equipped with
      continuous stiffness measurement and lateral-force measurement attachments. The
      results indicate that there is little change in the content of B, C, and N. The
      films deposited are compounds with hybridized B-C-N bonds and the disordered
      degree of the structure increases with increasing the substrate bias. The
      substrate biasing can enhance the nanohardness, elastic modulus, nano-scratch
      resistance, and cohesion strength of the deposited films. During the nano-scratch
      test, plastic deformation and ploughing wear appears for the BCN films deposited
      at lower bias. Elastic deformation becomes the dominant deformation mechanism for
      the films deposited at higher bias. The coefficient of friction between the
      deposited BCN films and the diamond tip depends on the loading critical load. The
      increasing of the substrate bias leads to the improvement of the critical load
      and the elastic deformation proportion.

PMID- 16792379
TI  - Synthesis and characterization of one-dimensional MgO nanostructures.
AB  - Magnesium oxide (MgO) nanowire arrays, nanoribbons, two- and three-dimensional
      network like nanostructures were prepared by the simple thermal evaporation of Mg
      powder with and without using catalyst at a relatively low temperature. The non
      catalytic approaches favor the formation of network like nanoforms whereas the
      catalytic approaches favors the formation of one-dimensional nanowire arrays and
      quasi one-dimensional nanoribbons depending on the temperature and vapor
      concentrations of the growth site. The diameter and length of the MgO network
      like columns varied within 40-50 nm and approximately 200 nm respectively. The
      MgO nanowires produced by the catalytic approach had diameter within 20-30 nm and
      length approximately 2 microm. Whereas the widths of the nanoribbons varied
      within 50-100 nm and their length were of the order of a few hundred micrometers.
      The nanoforms were single crystalline and cubic in phase. The products were
      characterized by the X-ray diffraction study, energy dispersive analysis of X-ray
      study, scanning and transmission electron microscopy, and photoluminescence
      measurements to explore the structural, compositional, morphological, and
      physical properties of the MgO nanoforms.

PMID- 16792380
TI  - DNA in nanopores: negative capacitance and delta-relaxation at high frequency.
AB  - We measured the high frequency dielectric relaxation behavior of DNA molecules
      confined in nanopores of polycarbonate membrane. The data revealed the existence
      of a critical frequency omega(c) approximately GHz at which the ac conductivity
      showed delta-relaxation. Interestingly, the DNA molecules also exhibited a
      crossover from positive to negative capacitance corresponding to omega(c). The
      negative capacitance at the critical frequency suggested a strong inductive
      behavior of DNA molecules in the high frequency regime. The results are
      interpreted in terms of the confined geometry of the DNA molecules in the
      nanopores. The interfacial water H-bonded to DNA played a crucial role in
      determining the high frequency relaxation of DNA molecules. The results indicated
      that the DNA in nanopores could be designed for application in high frequency
      bandpass/notch filters.

PMID- 16792381
TI  - Immobilization of functional oxide nanoparticles on silicon surfaces via Si-C
      bonded polymer brushes.
AB  - A method for immobilizing and mediating the spatial distribution of functional
      oxide (such as SiO2 and Fe3O4) nanoparticles (NPs) on (100)-oriented single
      crystal silicon surface, via Si-C bonded poly(3-(trimethoxysilyl)propyl
      methacrylate) (P(TMSPM)) brushes from surface-initiated atom transfer radical
      polymerization (ATRP) of (3-(trimethoxysilyl)propyl methacrylate) (TMSPM), was
      described. The ATRP initiator was covalently immobilized via UV-induced
      hydrosilylation of 4-vinylbenzyl chloride (VBC) with the hydrogen-terminated
      Si(100) surface (Si-H surface). The surface-immobilized Fe3O4 NPs retained their
      superparamagnetic characteristics and their magnetization intensity could be
      mediated by adjusting the thickness of the P(TMSPM) brushes.

PMID- 16792382
TI  - Alignment of glycolipid nanotubes on a planar glass substrate using a two-step
      microextrusion technique.
AB  - We have developed a two-step microextrusion technique to align lipid nanotubes of
      200 nm in diameter in parallel on planar glass substrates. This technique is
      useful to align self-assembled molecular nanofibers or nanotubes with diameters
      ranging from 100 to 300 nm. In the first step, we applied relatively large air
      pressure (approximately 40 hPa) onto a microcapillary filled with aqueous
      dispersion of lipid nanotubes to push them out. An aqueous droplet with 60 microm
      diameter was then extruded from the tip of the microcapillary. After one end of
      the lipid nanotube moved out, we changed the air pressure to be smaller,
      approximately 20 hPa to reduce the flow rate of the dispersion. The decrease in
      size of the droplet allowed us to fix the exposed end of the lipid nanotube onto
      the planar substrate. By dragging the microcapillary along the planar surface, we
      were able to align the whole nanotube onto the substrate. Using this technique,
      we have achieved the parallel alignment of the lipid nanotubes on the glass
      substrate.

PMID- 16792383
TI  - Silver nanoisland induced synthesis of ZnO nanostructures by vapor phase
      transport.
AB  - ZnO nanostructures including nanorod and nanotower were synthesized on Ag
      nanoisland coated Si substrate by thermal evaporation and vapor phase transport
      at atmospheric pressure. The as-prepared ZnO nanorods and nanotowers were single
      crystal growing along [0001] direction. The growth of ZnO nanostructures strongly
      depended on the surface morphology of the nanoisland Ag film deposited by
      electroless nanoelectrochemistry. The growth mechanism of the ZnO nanostructures
      was proposed on the basis of experimental data. A strong room-temperature
      photoluminescence in ZnO nanostructures has been demonstrated. The growth
      technique would be of particular interest for direct integration in the current
      silicon-technology-based optoelectronic devices.

PMID- 16792384
TI  - Comparison between an unipolar corona charger and a polonium-based bipolar
      neutralizer for the analysis of nanosized particles and biopolymers.
AB  - In this work we present results on the charging efficiency of nanoparticles by
      means of a corona based unipolar charging unit. This device was designed to
      replace a Po210 bipolar charger unit in a commercial electrospray aerosol
      generator (TSI Mod 3480). The charging efficiency has been investigated for
      negative and positive charged particles of various chemical composition in the
      size range between 5 and 18 nm. The corona current has been found to be the most
      influential operation parameter on the charging efficiency. With a positive
      electrospray droplet charge and a negatively-biased corona needle, a rapidly
      decreasing yield of singly positively charged aerosol particles with increasing
      corona current was found. An increasing yield of negatively charged particles was
      observed with increasing current of the corona process. Providing appropriate
      corona settings nanoparticles with charge levels similar to these obtained with a
      Po210 charger were found. At optimal corona settings the yield of singly charged
      particles was found to be two to four times higher for negative and positive
      particles compared to bipolar charging. This gain in the charging efficiency
      increases directly the sensitivity of analysis and enhances all measurement and
      manipulation processes of airborne nanoparticles for which electrical charging is
      required.

PMID- 16792385
TI  - A first-principle study of one-dimensional carbon atomic chain inserted single
      wall carbon nanotubes.
AB  - Using first principles calculations, we investigate the atomic and electronic
      structure of carbon nanowires (CNWs) as the carbon chain inserted into single
      wall carbon nanotubes (SWCNTs). It indicates that the (5,5) CNW system exhibits
      metallic character, however, the insertion of carbon chain can transit a semi
      conducting (9,0) SWCNT into a metallic.

PMID- 16792386
TI  - Synthesis of silicon nitride nanowires by the pyrolysis of perhydropolysilazane.
AB  - Silicon nitride nanowires synthesized by the pyrolysis of perhydropolysilazane
      without using any catalysts are reported. After pyrolysis at 1073 K in N2/NH3
      atmosphere, the synthetic nanowires are discrete and curly with diameters about
      tens of nanometers and lengths of hundreds of nanometers. While after post
      treatment at 1873 K in N2 atmosphere, the nanowires are continuous and randomly
      distributed with diameters about tens of nanometers and several microns in
      length. There are no bulbs or droplets on the tips of the nanowires, and two gas
      solid mechanisms are proposed to explain their growth.

PMID- 16792387
TI  - Aged-care support in Japan: perspectives and challenges.
AB  - This article explores economic aspects of the market for long-term care (LTC) in
      Japan. As the world's most rapidly aging nation, it is of interest to understand
      that country's current LTC system and projections of LTC utilization patterns and
      costs, as well as their potential drivers. Since Japan appears likely to
      experience important shortfalls in LTC in the future, the authors also discuss
      alternate forms of provision.

PMID- 16792388
TI  - Culture, infrastructure and international health benefits delivery.
AB  - When selecting a health insurance carrier for international employees, it is
      advantageous to recognize that valid assumptions made when selecting domestic
      benefits simply do not apply in the international realm and can lead to costly
      errors. This article examines some scenarios and cultural anomalies that
      invalidate commonly accepted domestic health insurance practices. It explores
      strategies for simplifying benefit design, providing access to quality care
      abroad, assessing costs, minimizing overseas risks and understanding the cultural
      impact on health care delivery.

PMID- 16792389
TI  - The employer's case for health management.
AB  - Employers' past solutions to rising health benefit costs--adopting managed care
      strategies, cost shifting to employees and reducing benefits-are no longer
      effectively controlling costs and are depressing the value of health benefits for
      employee recruitment and retention. An alternative strategy is to implement
      health management approaches that improve the health status of employees. These
      programs reduce medical costs and have a documented positive impact on workers'
      compensation, disability costs, absenteeism and productivity. Further, this
      approach is complementary to health care consumerism as a strategy for health
      improvement and benefit cost reduction and results in improved employee health,
      outlook and satisfaction.

PMID- 16792390
TI  - Manufacturing firms' decisions regarding retiree health insurance.
AB  - The trend for employers to discontinue offering retiree health insurance has
      profound implications for a large and growing share of the U.S. older population.
      The authors explore factors related to the firm's decision to offer and
      contribute to retiree health insurance using data from manufacturing firms. Their
      findings indicate that while firm characteristics, such as size and age, affect
      the probability that a firm offers retiree health insurance, employer
      contributions to this benefit are significantly related to the firm's financial
      performance and the alternative insurance options available in the market. The
      article concludes with a brief discussion of policy-related measures with
      potentially important implications for the future of retiree health benefits.

PMID- 16792391
TI  - Employers' liability risk for managed care injuries.
AB  - Concerns about employer liability are a major public policy barrier to expanding
      tort liability for managed health care organizations. To evaluate the extent of
      these legal concerns, interviews were conducted with key informants, selected to
      represent a range of legal and demographic characteristics nationwide. These
      subjects reported a low level of existing concern about liability arising from
      managed health care, and few indicated that an increase in this threat would
      likely cause them to drop health benefits. Instead, most said employers would
      take a wait-and-see approach to theoretical liability threats and would consider
      responses short of dropping coverage, such as switching to fully insured health
      benefits, or from defined benefits to defined contributions.

PMID- 16792392
TI  - HMOs--copayments. Lefler v. United Healthcare of Utah, Inc.

PMID- 16792393
TI  - Massachusetts offers a blueprint for change.

PMID- 16792394
TI  - How to plug revenue leaks.

PMID- 16792395
TI  - What one veteran taught me.

PMID- 16792397
TI  - What you learn when your son dies.

PMID- 16792396
TI  - Adding ancillaries. Holter monitoring.

PMID- 16792398
TI  - Follow-up tips for a safe, efficient practice.

PMID- 16792399
TI  - Doctors--the new target in the war on drugs?

PMID- 16792400
TI  - Your responsibility for informed consent.

PMID- 16792401
TI  - Ethyl-branched aldehydes, ketones, and diketones from caimans (Caiman and
      Paleosuchus; Crocodylia, Reptilia).
AB  - Secretions from the paracloacal glands of alligators (Alligator spp.) and caimans
      (Caiman spp., Melanosuchus niger, and Paleosuchus spp.) were examined by GC-MS.
      The secretions of the common caiman (C. crocodilus), the broad-snouted caiman (C.
      latirostris), the yacare caiman (C. yacare), the dwarf caiman (P. palpebrosus),
      and the smooth-fronted caiman (P. trigonatus) yielded a new family of 43
      aliphatic carbonyl compounds that includes aldehydes, ketones, and beta-diketones
      with an ethyl branch adjacent to the carbonyl group. The identification of these
      glandular components and the syntheses and stereochemical investigations of
      selected compounds are described.

PMID- 16792402
TI  - 10-Phenyl-[12]-cytochalasins Z7, Z8, and Z9 from the marine-derived fungus
      Spicaria elegans.
AB  - The three new 10-phenyl-[12]-cytochalasins Z7, Z8, and Z9 (1-3), together with
      two known analogues, cytochalasins E (4) and K (5), were isolated from the marine
      derived fungus Spicaria elegans. This is only the second report to date that
      cytochalasins contain a 12-membered macrocyclic ring. The structures of the three
      new cytochalasins were elucidated by spectroscopic methods, and their absolute
      configurations were determined for the first time by the modified Mosher's
      method. All five cytochalasins were evaluated for their cytotoxic effects on P388
      and A-549 cell lines by the MTT method.

PMID- 16792403
TI  - Coumestans from Hedysarum multijugum.
AB  - Ten coumestans were isolated from the roots of Hedysarum multijugum. Their
      structures were elucidated as the new hedysarimcoumestans A-H (1-8), 1,3,9
      trimethoxycoumestan (9), and aureol (10), on the basis of spectroscopic analyses.

PMID- 16792404
TI  - Glucosyloxybenzyl 2-Isobutylmalates from the tubers of Gymnadenia conopsea.
AB  - Seven new glucosyloxybenzyl 2-isobutylmalates, gymnosides I-VII (1-7), were
      isolated from the tubers of Gymnadenia conopsea. The structures of 1-7 were
      determined on the basis of chemical and physicochemical evidence.

PMID- 16792405
TI  - Nitrogen-containing phorbol esters from Croton ciliatoglandulifer and their
      effects on cyclooxygenases-1 and -2.
AB  - Four new phorbol derivatives, 12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4
      deoxyphorbol 13-acetate (1), 12-O-[(2S)-N,N-dimethyl-3-methylbutanoyl]-4
      deoxyphorbol 13-acetate (2), 12-O-[3-methyl-2-butenoyl]-4-deoxyphorbol 13-acetate
      (3), and 12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]phorbol 13-acetate (4), along
      with six known compounds, were isolated from the aerial parts of Croton
      ciliatoglandulifer. An anti-inflammatory activity of a hexane extract of this
      plant was demonstrated against ear edema in mice produced by 12-O
      tetradecanoylphorbol 13-acetate, and compounds 1, 4, and 3beta-O-acetyloleanolic
      acid (5) were active when evaluated against cyclooxygenases-1 and -2.

PMID- 16792406
TI  - Antifungal azaphilones from the fungus Chaetomium cupreum CC3003.
AB  - Three new azaphilones named rotiorinols A-C (1-3), two new stereoisomers, (-)
      rotiorin (4) and epi-isochromophilone II (5), and a known compound, rubrorotiorin
      (6), were isolated from the fungus Chaetomium cupreum CC3003. Structures were
      established on the basis of spectroscopic evidence. The absolute configuration of
      1 was determined by the modified Mosher's method along with an X-ray analysis of
      its acetate derivative, as well as by chemical transformation. Compounds 1, 3, 4,
      and 6 exhibited antifungal activity against Candida albicans with IC50 values of
      10.5, 16.7, 24.3, and 0.6 microg/mL, respectively.

PMID- 16792407
TI  - Characterization of pentasaccharide glycosides from the roots of Ipomoea
      arborescens.
AB  - Ten new pentasaccharide glycosides, arboresins 1-6 (1-6) and murucins 6-9 (8-11),
      along with five known glycolipids, were isolated from the roots of Ipomoea
      arborescens, and their structures were elucidated by spectroscopic and chemical
      methods. Compounds 1-6 and 8-11 were evaluated for cytotoxicity against a small
      panel of cancer cell lines.

PMID- 16792408
TI  - Spasmolytic effects of nonprenylated rotenoid constituents of Boerhaavia diffusa
      roots.
AB  - Boerhaavia diffusa is an Ayurvedic remedy used traditionally for the treatment of
      a number of diseases, including those affecting the gastrointestinal tract. In
      the current investigation, a methanol extract obtained from roots of B. diffusa
      exhibited a significant spasmolytic activity in the guinea pig ileum, probably
      through a direct effect on the smooth muscle. A detailed phytochemical analysis
      of this methanol extract led to the isolation of one new (12) and six known (6
      11) rotenoid derivatives. The structure of the new compound was determined
      through interpretation of its MS and NMR data. All the isolated rotenoids were
      evaluated for their effect on intestinal motility in vitro, and the results
      obtained showed unambiguously that they are active spasmolytic constituents.
      Preliminary structure-activity relationships for this class of compounds are
      suggested.

PMID- 16792409
TI  - Mono-, Bi-, and triphenanthrenes from the tubers of Cremastra appendiculata.
AB  - Six newphenanthrene derivatives, including three monophenanthrenes (1-3), two
      biphenanthrenes (4 and 5), and a triphenanthrene (6), have been isolated from an
      ethanolic extract of the tubers of Cremastra appendiculata. Using spectroscopic
      methods, the structures of compounds 1-6 were determined as 1-hydroxy-4,7
      dimethoxy-1-(2-oxopropyl)-1H-phenanthren-2-one (1), 1,7-dihydroxy-4-methoxy-1-(2
      oxopropyl)-1H-phenanthren-2-one (2), 2-hydroxy-4,7-dimethoxyphenanthrene (3),
      2,7,2'-trihydroxy-4,4',7'-trimethoxy-1,1'-biphenanthrene (4), 2,2'-dihydroxy
      4,7,4',7'-tetramethoxy-1,1'-biphenanthrene (5), and 2,7,2',7',2' '-pentahydroxy
      4,4',4' ',7' '-tetramethoxy-1,8,1',1' '-triphenanthrene (6), respectively.
      Compounds 1-6 and two known compounds, cirrhopetalanthin (7) and flavanthrinin
      (8), obtained previously from this plant, were evaluated against six human cancer
      cells and a normal cell line.

PMID- 16792410
TI  - Synthesis of salvinorin A analogues as opioid receptor probes.
AB  - Several neoclerodanes, such as salvinorin A (1) and herkinorin (3), have recently
      been shown to possess opioid receptor activity in vitro and in vivo. To explore
      the structure-affinity relationships of this interesting class of compounds, we
      have synthesized a series of analogues from 1 isolated from Salvia divinorum.
      Here, we report the semisynthesis of neoclerodane diterpenes and their structure
      affinity relationships at opioid receptors. This work will allow the further
      development of novel opioid receptor ligands.

PMID- 16792411
TI  - Triterpenoid saponins from the fruits of Caryocar villosum.
AB  - Fourteen new triterpenoid saponins (1-14) were isolated from the methanol extract
      of the fruits of Caryocar villosum along with 10 known saponins. Their structures
      were established on the basis of extensive NMR (1H, 13C, COSY, TOCSY, ROESY,
      HSQC, and HMBC) and ESIMS studies. The toxicity of the methanolic extracts of the
      peel and the pulp of fruits and the crude saponin fraction of the peel was
      assessed using the Artemia salina test. The antimicrobial activities of
      caryocarosides IV-21 (14), II-1 (16), III-1 (17), and IV-9 (20) and of saponin 23
      were also studied in vitro on Escherichia coli, Staphylococcus aureus,
      Pseudomonas aeruginosa, Mycobacterium smegmatis, and Enterococcus faecalis
      bacteria.

PMID- 16792412
TI  - Chemical and cytotoxic constituents from the leaves of Cinnamomum kotoense.
AB  - Three new butanolides, kotomolide A (1), isokotomolide A (2), and kotomolide B
      (3), and a new secobutanolide, secokotomolide A (4), along with 21 known
      compounds were isolated from the leaves of Cinnamomum kotoense. Their structures
      were determined by spectroscopic analyses. Compound 4 was found to induce
      significant cell death in the human HeLa cell line. Apoptotic-related DNA damage
      can be positively related to the dose of compound 4. The DNA damage was measured
      by the percentage of subG1 (24 h after the treatment of compound 4) as determined
      by cell cycle analysis and TUNEL assay. Treatment with 4 significantly increased
      intracellular H2O2 and/or peroxide, nitric oxide (NO) at 1, 3, and 24 h. Our
      results also showed that compound 4 induced (a) noticeable reduction of
      mitochondrial transmembrane potential (DeltaPsi(m)), (b) activation of caspase
      3/7, and (c) up-regulation of the p53 expression. Compound 4-induced DNA damage
      was found to markedly decrease when the cells were pretreated with an
      intracellular glutathione supplement (glutathione ethyl ester). These results
      suggest that an increase of H2O2 and/or peroxide by compound 4 is the initial
      apoptotic event. The intracellular GSH depletion is a critical event in compound
      4-induced apoptosis in HeLa cells.

PMID- 16792413
TI  - Stellettin A induces oxidative stress and apoptosis in HL-60 human leukemia and
      LNCaP prostate cancer cell lines.
AB  - The present study has demonstrated a differential cytotoxicity of stellettin A
      (1) between human leukemia HL-60 cells (IC50 0.4 microg/mL) and human prostate
      cancer LNCaP cells (IC50 120 microg/mL). Treatment of cells with 1 revealed the
      activation of NADPH oxidase, the dramatic generation of reactive oxygen species,
      and the dissipation of mitochondrial membrane potentials, with HL-60 cells being
      more sensitive than LNCaP cells by an order of magnitude. Immunoblotting analysis
      further demonstrated a stronger upregulation of the apoptosis marker proteins,
      FasL and caspase-3, in HL-60 cells, and pretreatment of cells with antisense
      oligonucleotide for caspase-3 abolished apoptosis. All available evidence
      suggests that 1 induces oxidative cell death through a FasL-caspase-3-apoptotic
      pathway.

PMID- 16792414
TI  - Characterization of the initial enzymatic steps of barbamide biosynthesis.
AB  - Barbamide is a mixed polypeptide-polyketide natural product that contains an
      unusual trichloromethyl group. The origin of the trichloromethyl group was
      previously shown to be through chlorination of the pro-R methyl group of L
      leucine. Trichloroleucine is subsequently decarboxylated and oxidized to
      trichloroisovaleric acid and then extended with an acetate unit to form the
      initial seven carbons of barbamide. In this study we used a combination of
      biosynthetic feeding experiments and enzymatic analysis to characterize the
      initial steps required for formation of trichloroleucine and its chain-shortened
      product, trichloroisovaleric acid. Results from isotope-labeled feeding
      experiments showed that both dichloroleucine and trichloroleucine are readily
      incorporated into barbamide; however, monochloroleucine is not. This suggests
      that halogenation of the pro-R methyl group of leucine occurs as two discrete
      reactions, with the first involving incorporation of at least two halogen atoms
      and the second converting dichloroleucine to trichloroleucine. Additionally, the
      initial tandem dichlorination must occur before substrate can be further
      processed by the remainingbar pathway enzymes. In vitro analysis of the first
      five open reading frames (ORFs; barA, barB1, barB2, bar C, barD) of the barbamide
      gene cluster has yielded new insights into the processing of leucine to form the
      trichloroisovaleryl-derived unit in the final product.

PMID- 16792415
TI  - Quercetin as the active principle of Hypericum hircinum exerts a selective
      inhibitory activity against MAO-A: extraction, biological analysis, and
      computational study.
AB  - The methanol extract from Hypericum hircinum leaves exhibited in vitro inhibition
      of monoamine oxidases (MAO). Bioassay-guided fractionation led to the isolation
      of quercetin and five compounds identified for the first time from H. hircinum.
      Quercetin was the only compound with a selective inhibitory activity against MAO
      A, with an IC50 value of 0.010 microM. To explain MAO selective inhibition at the
      molecular level, a computational study was carried out by conformational search
      and docking techniques using recently determined crystallographic models of both
      enzymatic isoforms. An in vivo study in mice was carried out using the forced
      swimming test in order to elucidate the behavioral effects of quercetin.

PMID- 16792416
TI  - Euphoportlandols A and B, tetracylic diterpene polyesters from Euphorbia
      portlandica and their anti-MDR effects in cancer cells.
AB  - Two new tetracyclic diterpene polyesters, euphoportlandols A (1) and B (2), have
      been isolated along with 12 known tetracyclic triterpenes from an acetone extract
      of Euphorbia portlandica. Their structures were established as
      5alpha,11alpha,14alpha,17-tetraacetoxy-3beta-benzoyloxy-6beta,15beta-dihydroxy-9
      oxoseget-8(12)-ene (1) and 5alpha,11alpha,14alpha,17-tetraacetoxy-3beta
      benzoyloxy-6beta,15beta-dihydroxy-9-oxosegetane (2), respectively, by
      spectroscopic data interpretation. Compounds 1 and 2 were evaluated for their
      ability to inhibit multidrug resistance in cancer cells. Both compounds were
      found to be inhibitors of P-glycoprotein activity.

PMID- 16792417
TI  - Revision of the structure of escholidine.
AB  - The structure of the quaternary tetrahydroprotoberberine alkaloid escholidine is
      revised on the basis of 2D NMR spectroscopy and X-ray diffraction. In contrast to
      the originally reported constitution, escholidine bears an -OH group at C-9 and
      an -OCH3 group at C-10. The 1H and 13C NMR data and long-range 1H-13C and NOE
      interactions of escholidine are compared with those of thalifendine and
      tetrahydroberberrubine. The 15N NMR data of escholidine obtained by using long
      range 1H-15N correlation experiments at natural abundance are also reported.

PMID- 16792418
TI  - Biotransformation of (-)-ambrox by cell suspension cultures of Actinidia
      deliciosa.
AB  - Biotransformation of (-)-ambrox (1) with cell suspension cultures of Actinidia
      deliciosa (Kiwifruit) yielded the regio- and stereospecific oxygenated products 3
      oxoambrox (2), 3beta-hydroxyambrox (3), 1alpha-hydroxyambrox (4), 3beta,6beta
      dihydroxyambrox (5), 1alpha,6beta-dihydroxyambrox (6), and 1alpha,3beta
      dihydroxyambrox (7). Metabolites 6 and 7 were found to be new compounds. These
      metabolites were structurally characterized on the basis of spectroscopic
      studies. The structure of compound 6 was unambiguously deduced by single-crystal
      X-ray diffraction techniques. Metabolites 2-7 were evaluated for in vitro
      inhibitory activity against the thymidine phosphorylase enzyme.

PMID- 16792419
TI  - ent-Trachylobane diterpenoids from Xylopia langsdorffiana.
AB  - Two new diterpenes of the ent-trachylobane type were isolated from the stems of
      Xylopia langsdorffiana, ent-7alpha-acetoxytrachyloban-18-oic acid (1) and ent
      7alpha-hydroxytrachyloban-18-oic acid (2). The structures of these isolates were
      deduced by spectroscopic data interpretation. X-ray crystallography of 1 was used
      to confirm its structure. The cytotoxic activity of 1 against V79 fibroblasts and
      rat hepatocytes was investigated.

PMID- 16792420
TI  - C18 dibenzocyclooctadiene lignans from Kadsura philippinensis.
AB  - Four new C18 dibenzocyclooctadiene lignans, kadsuphilins A (1) and B (3), 6-epi
      gomisin (2), and 1-demethylkadsuphilin A (4), along with eight known related
      metabolites, were isolated from an EtOAc fraction of an alcoholic extract of the
      aerial parts of Kadsura philippinensis growing in Taiwan. The structures of 1-4
      were elucidated on the basis of spectroscopic analyses, including 2D NMR (HMQC,
      HMBC, and NOESY) experiments, and by comparison of their spectroscopic data with
      those of related metabolites. The configurations of the biphenyl and
      cyclooctadiene moieties were deduced from circular dichroism (CD) and NOESY NMR
      spectra, respectively. Some of the compounds showed radical-scavenging activity
      in a DPPH-HPLC method.

PMID- 16792421
TI  - Diterpenoids from the roots of Euphorbia fischeriana.
AB  - From the dried roots of Euphorbia fischeriana, seven new diterpenoids, 3alpha,17
      dihydroxy-ent-pimara-8(14),15-diene (1), 7beta,11beta,12beta-trihydroxy-ent
      abieta-8(14),13(15)-dien-16,12-olide (2), 17-acetoxyjolkinolide B (3), 13beta
      hydroxy-ent-abiet-8(14)-en-7-one (4), 12-deoxyphorbaldehyde-13-acetate (5) 12
      deoxyphorbaldehyde-13-hexadecacetate (6), and 12-deoxyphorbol-13-(9Z)
      octadecanoate-20-acetate (7), and two known compounds, 12-deoxyphorbol-13
      decanoate (8) and prostratin (9), were isolated. The structures of the new
      compounds were elucidated on the basis of spectroscopic analysis. The structure
      of compound 1 was confirmed by single-crystal X-ray crystallography. Compounds 3
      and 8 exhibited potent cytotoxic activity to Ramos B cells with IC50 values of
      0.023 and 0.0051 microg/mL, respectively.

PMID- 16792422
TI  - Iridoid constituents of Tarenna attenuata.
AB  - Members of a rare type of iridoid with two alpha,beta-unsaturated acid units were
      isolated from the whole plant of Tarenna attenuata, including a new compound,
      tarennin (1), an extraction artifact, and seven new glucosides, tarenninosides A
      G (2-8), together with two known iridoid glucosides, ixoside and 10
      methylixoside. The structures of 1-8 were elucidated by analysis of spectroscopic
      data including HMQC, HMBC, 1H-1H COSY, and ROESY NMR spectra and by comparison
      with known analogues. Antioxidant and cytotoxic activities were evaluated for
      these 10 compounds, but none showed positive activity.

PMID- 16792423
TI  - Musidunin and musiduol, insect antifeedants from Croton jatrophoides.
AB  - Two novel limonoids, musidunin (1) and musiduol (2), were isolated from a
      methanol extract of Croton jatrophoides by bioassay-guided fractionation. Their
      structures were established by extensive NMR experiments. Interestingly, A,B-seco
      limonoid 1 contains a unique acetal annulation of A, A', and B' rings. Both
      limonoids exhibited antifeedant activities against two pests, Pectinophora
      gossypiella and Spodoptera frugiperda.

PMID- 16792424
TI  - In vivo wound-healing activity of oleanolic acid derived from the acid hydrolysis
      of Anredera diffusa.
AB  - Anredera diffusa is used as a wound-healing agent in traditional Peruvian
      medicine. Acid hydrolysis of the bioactive ethanolic extract, followed by in vivo
      activity-guided fractionation, yielded oleanolic acid, with a wound-healing
      activity equivalent to 42.9% (p < 0.01) above the control. The highest
      cicatrizant activity in mice was obtained by applying 40 microg of oleanolic acid
      per gram of body weight.

PMID- 16792425
TI  - Chromone derivatives from the filamentous fungus Lachnum sp. BCC 2424.
AB  - Five new chromones, named lachnones A-E (1-5), were isolated from the filamentous
      fungus Lachnum sp. BCC 2424 along with known (2E,6S)-2,6-dimethyl-2,7-octadiene
      1,6-diol. Their structures were elucidated by spectroscopic methods. Lachnones B
      (2) and D (4) mildly inhibited the growth of Mycobacterium tuberculosis, both
      with MIC values of 200 microg/mL.

PMID- 16792426
TI  - Bidirectional effects of expressed emotion and behavior problems and symptoms in
      adolescents and adults with autism.
AB  - Expressed emotion measures the emotional climate of the family and is predictive
      of symptom levels in a range of medical and psychiatric conditions. This study
      extends the investigation of the effects of expressed emotion to families of
      individuals with autism. A sample of 149 mothers co-residing with their
      adolescent or adult child with autism over an 18-month period was drawn from a
      large multiwave longitudinal study. High expressed emotion was related to
      increased levels of maladaptive behavior and more severe symptoms of autism over
      time. Also, characteristics of the son or daughter influenced levels of maternal
      expressed emotion over time. Although autism is a complex genetic disorder, the
      effect of the family environment in shaping the behavioral phenotype should not
      be underestimated.

PMID- 16792428
TI  - Young children with developmental delays as young adults: predicting
      developmental and personal-social outcomes.
AB  - We report on a 20-year follow-up of 30 children with developmental delays
      identified at age 3. Our purpose was to assess the relationship of early
      indicators of delay to cognitive and personal-social status in young adulthood.
      Predictors were Developmental and Personal-Social factors derived from
      standardized tests and parent questionnaires administered when the children were
      3 and 6 to 7. Outcome measures in young adulthood included standardized and
      project-developed questionnaires and interviews with young adults and parents.
      Findings indicate that prediction varies relative to the outcome assessed.
      Developmental status at 6 to 7 was a strong predictor of developmental status in
      young adulthood. However, personal-social outcomes were generally not predicted
      by Personal-Social factors in the early years.

PMID- 16792427
TI  - Hispanic caregivers of adults with mental retardation: importance of family
      functioning.
AB  - Our aim in this study was to validate a stress-process model for Hispanic
      caregivers of adults with mental retardation that incorporates family
      functioning. The model postulates that maladaptive adult behaviors are related to
      poorer family relationships and higher levels of family burden, which in turn is
      related to caregiver psychological distress and self-reported health. The 153
      Hispanic caregivers were interviewed in their homes with structured interviews
      and self-report measures. We analyzed cross-sectional data using structural
      equation modeling. The hypothesized model provided an excellent fit to the data.
      Also, family relationships mediated the relationship between maladaptive adult
      behaviors and family burden, and higher levels of family burden were related to
      greater caregiver distress. Acculturation was negatively related to caregiver
      distress.

PMID- 16792429
TI  - Analysis of mother-infant interaction in infants with down syndrome and typically
      developing infants.
AB  - Delays in development of early social behaviors in babies with Down syndrome are
      likely to affect patterns of interaction with their caregivers. We videotaped 23
      babies in face-to-face interaction with their mothers at 8 and 20 weeks of age
      and compared them to 23 typically developing infants and their mothers. Social
      behaviors, mothers' behaviors, and quality of interaction were rated. At 8 weeks,
      babies with Down syndrome were significantly less communicative and lively than
      the typically developing babies. Their mothers' behaviors did not differ at 8
      weeks, but did at 20 weeks. Although the social behaviors of babies with Down
      syndrome improved over time, qualitative differences remained.

PMID- 16792430
TI  - Behavioral treatment of challenging behaviors in individuals with mild mental
      retardation: meta-analysis of single-subject research.
AB  - A meta-analytic study on effectiveness of behavioral and psychotherapeutic
      treatments for challenging behaviors in individuals with mild mental retardation
      is reported. Eighty articles were examined. For each comparison, several study
      variables and two effect sizes (percentage of nonoverlapping data-PND and
      percentage of zero data-PZD) were evaluated (Ms = 75% and 35%, respectively).
      Studies in which experimental designs and methods of experimental functional
      analysis were used had significantly larger PNDs than those with AB designs and
      descriptive methods, respectively. Functional analysis, reliability of recording,
      generalization, and internally valid designs resulted in larger PZDs. We found
      that behavioral interventions for challenging behaviors are effective with people
      with mild mental retardation.

PMID- 16792431
TI  - Tracking preschool children with developmental delay: third grade outcomes.
AB  - Educational outcomes were evaluated for 2,046 preschool children identified with
      developmental delay. Results indicated that at third grade, 26% were in regular
      education and the remaining 74% were receiving special education services. The
      most common disability classifications at outcome were specific learning
      disabilities and educable mentally handicaps. Regular education, but not special
      education, children had higher retention rates than did the general population.
      The presence of one or more secondary exceptionalities in preschool was more
      common for special education than regular education children. Regular education
      and special education children did not differ on other factors studied. This
      study highlights the importance of developmental delay as an exceptionality
      category and advances our understanding of the long-term implications of such
      delay.

PMID- 16792433
TI  - The state of child health and human rights in Nepal.

PMID- 16792434
TI  - Training and HIV-treatment scale-up: establishing an implementation research
      agenda.

PMID- 16792435
TI  - Utilization and drug cost outcomes of a step-therapy edit for generic
      antidepressants in an HMO in an integrated health system.
AB  - OBJECTIVE: Antidepressants do not differ significantly in their ability to treat
      depression. Excluding the tricyclic antidepressants (TCAs), these drugs also do
      not differ significantly in their incidence of adverse events. Therefore, the
      initial choice of antidepressant medication should be based, in part, on cost.
      The objective of this study was to evaluate the impact on utilization and costs
      of a generic steptherapy edit for antidepressant drugs excluding TCAs in a health
      maintenance organization (HMO) in an integrated health system (IHS). METHODS: The
      pharmacy department of the 440,000-member HMO in an IHS collaborated with the
      Behavioral Health Clinical Program to design an intervention that required
      generic antidepressants as first-line pharmacotherapy. Under the GenericStart!
      Program, a brand-name antidepressant was covered only after trial with a generic
      antidepressant, excluding TCAs. A step-therapy edit was added to the pharmacy
      claims processing system on January 1, 2005. All new starts, defined as members
      with no claims history of antidepressant treatment within the preceding 6 months,
      were required to use a generic antidepressant. The member copayment was waived
      for the first prescription. All generic antidepressants were in tier 1 of the
      drug formulary, with an average copayment of $5 to $10. All brand-name
      antidepressants were in either tier 2 (preferred brand), with an average
      copayment of $20 to $25 or 25% coinsurance, or tier 3 (nonformulary brand), with
      an average copayment of $40 to $45 or 50% coinsurance. Pharmacy claims data from
      a national pharmacy benefit manager (PBM) without interventions for
      antidepressants in 2004 or 2005 were used for the comparison group. RESULTS: The
      generic antidepressant dispensing rate increased by 20 points (32.5% to 52.5%) in
      the intervention group but only 7.4 points (24.9% to 32.3%) in the comparison
      group in 2005 compared with 2004. The principal measure of antidepressant drug
      cost per day of therapy in the intervention group decreased by 11.7% (from $2.40
      to $2.12) in 2005 compared with 2004 versus a 2.7% decrease (from $2.60 to $2.53)
      in the comparison group (P <0.001). Days of antidepressant drug therapy per
      member per month (PMPM) dropped by 1.5% (from 1.74 to 1.71) in the intervention
      group versus a decrease of 5.0% (from 1.37 to 1.30) in the comparison group in
      2005 compared with 2004. The combination of change in drug cost and utilization
      resulted in a 13.0% decrease in antidepressant drug cost, from $4.16 PMPM in 2004
      to $3.62 in 2005, compared with a 7.6% decrease (from $3.57 to $3.30 PMPM) in the
      comparison group. The 9.0% difference in drug cost per day represents drug cost
      savings of approximately $0.36 PMPM or $1,880,562 in 2005 dollars for this HMO of
      approximately 440,000 members. CONCLUSION: A step-therapy edit requiring HMO
      members to use a generic antidepressant, excluding tricyclics, prior to use of a
      brand-name antidepressant resulted in drug cost savings of 9.0% for the entire
      class of antidepressants, equal to $1,880,562 ($0.36 PMPM) in 2005 dollars in the
      first year of the intervention. A small (-1.5%) decrease in use of
      antidepressants occurred in the intervention group, which was less than the 5.0%
      decrease in utilization of antidepressants in the comparison group.

PMID- 16792436
TI  - Blood pressure goal attainment according to JNC 7 guidelines and utilization of
      antihypertensive drug therapy in MCO patients with type 1 or type 2 diabetes.
AB  - OBJECTIVE: Controlling hypertension (HTN) in patients with diabetes mellitus (DM)
      can reduce complications such as nephropathy, cerebrovascular disease, and
      cardiovascular disease. As part of a quality improvement project with a managed
      care organization (MCO), we evaluated blood pressure (BP) control relative to the
      type of drug therapy for patients with type 1 or type 2 DM who were identified
      from pharmacy claims for antihyperglycemic drug therapy. METHODS: Pharmacy claims
      for antihyperglycemic drugs, including insulin, were used to identify a random
      sample of commercial members in an MCO comprising 30 health plans across the
      United States. Retrospective medical record review was conducted in October 2003
      to collect data from 4,814 patient charts. BP goal attainment according to The
      Seventh Report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines was
      determined for each patient from the most recent BP reading documented in the
      medical chart. RESULTS: The distribution by type of DM was 21.0% (n = 1,011) for
      type 1, 75.7% (n = 3,644) for type 2, and 3.3% (n = 159) for cases not documented
      in the medical chart. Excluding 590 charts (12.3%) without BP values, there were
      1,328 of 4,224 DM patients (31.4%) at JNC 7 BP goal (< 130/80 mm Hg). Of the
      1,328 patients at JNC 7 BP goal, 577 (43.4%) were at JNC 7 BP goal with no drug
      therapy. Excluding the 577 patients who did not require drug therapy to reach JNC
      7 goal, 751 (20.6%) of the remaining 3,647 patients who required antihypertensive
      drug therapy were at JNC 7 BP goal, and 788 (21.6%) received no antihypertensive
      drug therapy. For the population of 4,224 DM patients with a BP value recorded in
      the chart, application of the lower BP goals in the JNC 7 guidelines reduced the
      proportion with controlled BP to 31.4% (1,328/4,224) from 42.6% (1,799/4,224)
      according to the former JNC 6 guidelines (P < 0.01). The proportion of DM
      patients with HTN was 59.6% (n = 2,870), and 28.4% (n = 814) of these patients
      were not taking either an angiotensin-converting enzyme inhibitor (ACEI) or an
      angiotensin receptor blocker (ARB). There were 704 patients with albuminuria or
      nephropathy (14.6%), of which 35.4% (n = 249) were not taking either an ACEI or
      an ARB, preferred therapy in these patients. CONCLUSION: In this population of
      MCO members with DM for whom a BP value was recorded in the medical chart, 13.7%
      met JNC 7 BP goal with no antihypertensive drug therapy. For the patients with DM
      who received antihypertensive drug therapy and had a BP value recorded in the
      medical chart, only 26.3% were at JNC 7 BP goal. The application of JNC 7
      guidelines significantly reduced the proportion of DM patients at target BP goal
      from 42.6%% to 31.4%

PMID- 16792437
TI  - Administrative claims analysis of asthma-related health care utilization for
      patients who received inhaled corticosteroids with either montelukast or
      salmeterol as combination therapy.
AB  - OBJECTIVE: To compare asthma-related health care resource utilization among a
      matched cohort of asthma patients using inhaled corticosteroids (ICSs) plus
      either montelukast (MON) or salmeterol (SAL) as combination therapy for asthma,
      during a time prior to the availability of fixed-dose combinations of ICS/SAL.
      METHODS: A retrospective analysis using the PHARMetrics patient-centric claims
      database was conducted for the period preceding the market introduction of
      combination fluticasone-SAL in September 2000. Patients had to meet the following
      criteria for inclusion in the study: they had to be between the ages of 4 and 55
      years; they had to have been continuously enrolled for 2 years; they had to have
      initiated ICS/MON or ICS/SAL therapy between July 1, 1998, and June 30, 1999; and
      they had to have had either (a) a diagnosis of asthma (based on International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
      codes of 493.xx) for 2 outpatient visits, 1 or more emergency department (ED)
      visits, or 1 or more hospitalizations within 1 year or (b) pharmacy claim records
      that contained a National Drug Code for an antiasthma medication (betaagonist,
      theophylline, ICS, cromolyn, or leukotriene) 2 or more times within 1 year.
      ICS/MON and ICS/SAL patients were matched 1 to 1 on age and propensity score.
      Outcomes included asthma-related hopitalizations and ED visits with ICD-9-CM
      codes of 493.xx, and oral corticosteroid (OCS) fills and short-acting beta
      agonist (SABA) fills. Multivariate regression analyses were performed. Subgroup
      analyses based on sequential or concurrent initiation of combination therapy were
      also conducted. RESULTS: A total of 1,216 patients were matched (ICS/MON = 608;
      ICS/SAL= 608). Decreased odds of ED visits and/or hospitalizations were observed
      with ICS/MON (adjusted odds ratio [OR] = 0.58; 95% confidence interval [CI], 0.35
      0.98) versus ICS/SAL. The odds of postindex OCS fills were not different for
      ICS/MON and ICS/SAL patients (adjusted OR = 1.04; 95% CI, 0.79-1.38). Postindex
      pharmacy claims for SABAs were significantly higher among ICS/MON patients versus
      ICS/SAL patients (adjusted relative risk [RR] = 1.33; 95% CI, 1.17-1.52), and
      this difference remained regardless of prior use or no prior use of ICSs. In
      subgroup analyses, mean change in SABA fills varied by how combination therapy
      was initiated, with sequential addition of asthma controllers leading to a
      reduction in SABA fills in both groups. For patients with concurrent initiation
      of combination therapy, the odds of ED visits/hospitalizations were significantly
      lower in patients initiating ICS/MON (adjusted OR = 0.25; 95% CI, 0.08-0.79).
      CONCLUSION: In this matched cohort, use of ICS/MON compared with ICS/SAL resulted
      in similar odds of OCS fills, decreased odds of ED visits and asthmarelated
      hospitalizations, but higher utilization of SABA.

PMID- 16792438
TI  - The cost-effectiveness of lamotrigine in the maintenance treatment of adults with
      bipolar I disorder.
AB  - OBJECTIVE: To present an economic model and cost-effectiveness estimates for
      lamotrigine in maintenance treatment of bipolar I disorder (BD-I) using outcomes
      from the pivotal lamotrigine trials. The main comparator treatments in the
      pivotal trials were lithium and .no maintenance. (acute-only) treatment. A
      comparison with olanzapine was included as an indirect analysis following
      publication of data during the course of our research. METHODS: A Markov model
      was built around the 3 health states of euthymia, mania, and depression. The base
      case model simulates a cohort of 1,000 patients with BD-I who have recently
      stabilized after resolution of a bipolar mania episode. The cohort was modeled
      for a period of 18 months. Resource-use estimates were derived from best
      available published data, treatment guidelines, a physician survey, and published
      unit cost data. Outputs were measured in terms of costs per acute mood episode
      avoided, costs per euthymic day gained, and costs per quality-adjusted life-years
      (QALYs). Direct health care payer costs are used in the analyses. RESULTS: The
      base-case model for patients with a recent manic episode indicated that
      lamotrigine is the most effective treatment for avoiding both acute depression
      episodes and all types of acute episodes (depression and mania). It is also the
      most effective treatment in terms of number of euthymic days achieved (309 days
      per patient per year). Olanzapine is most effective for avoiding acute mania
      episodes. Total direct costs of treatment are lowest for the lithium treatment
      arm (Dollars 8,710 per patient for the 18-month period). All maintenance
      therapies were cost effective compared with the no-maintenance (acute-only
      treatment) arm. In the base case, lamotrigine had incremental cost-effectiveness
      ratios of Dollars 30 per euthymic day and Dollars 2,400 per acute episode avoided
      compared with lithium. A QALY analysis indicated that lamotrigine is cost
      effective in patients with a recent manic episode at Dollars 26,000 per QALY. The
      base-case model indicated that lamotrigine dominates olanzapine, (that is,
      lamotrigine costs less and is more effective than olanzapine) in patients with a
      recent manic episode. In a sensitivity analysis using outcomes from the pivotal
      trial of recently depressed patients, lamotrigine, in comparison with lithium,
      was not shown to be as cost effective as in the recently manic patients, but it
      was still cost effective compared with no maintenance treatment. CONCLUSIONS: For
      a defined cohort of patients with BD-I, the pharmacoeconomic model indicated that
      prevention of mood episodes with lithium and lamotrigine is cost effective in
      patients with a recent manic, mixed, or hypomanic episode. The conclusions with
      respect to the indirect comparison with olanzapine should be validated if and
      when direct trial data become available. Cost-effectiveness of maintenance
      treatments for patients with BD-I (recently depressed as well as recently manic)
      are likely to improve in models with a broader costing perspective and that take
      a longer time frame. Further research into the outcome implications of health
      related quality of life and other BD subgroups are recommended.

PMID- 16792439
TI  - Drug and medical cost effects of a drug formulary change with therapeutic
      interchange for statin drugs in a multistate managed Medicaid organization.
AB  - OBJECTIVE: Therapeutic interchange (TI) interventions are commonly used to manage
      pharmacy benefit costs. While several studies have considered the effect that TI
      interventions have on drug costs, most have not considered the effect they have
      on medical management costs. The purpose of the present study was to assess drug
      cost and drug therapy management costs of a TI intervention following a change in
      the drug formulary for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitor (statin) drugs, including the conversion of atorvastatin from formulary
      to nonformulary status. METHODS: A retrospective, quasi-experimental within
      subjects design was used in this study. Administrative claims data were obtained
      from a select northeastern segment of a multistate Medicaid managed care
      organization (MCO). To be included in the study, patients had to meet the
      following criteria: (1) they must have had a minimum of 3 atorvastatin
      prescriptions during a 6-month enrollment phase, (2) they must have been
      continuously enrolled throughout the 900-day study period, and (3) they must have
      switched from atorvastatin to another statin between April 1, 2003, and July 31,
      2003. The day of the switch from atorvastatin marked for each patient the end of
      the 12-month pre-TI period and the beginning of the 12-month post-TI period. Two
      separate dependent variables were developed: (1) statin drug costs (statin cost +
      dispensing fee) and (2) the costs paid by the MCO for the medical management of
      statin therapy, including office visit costs and the medical laboratory costs of
      measuring lipids and creatine kinase, and of checking liver functions. To
      estimate expenditures over 24 months, a panel analytic technique was used that
      allows each patient to serve as his or her own control. Multivariate models were
      used to assess the effects of the TI policy while controlling for age, gender,
      adjunctive dyslipidemia therapy, comorbidity, presence of a prior coronary artery
      event, statin compliance, cardiologist management, and disease severity. RESULTS:
      Of the 3,636 patients who met the study inclusion criteria and were converted
      from atorvastatin to an alternate statin drug, 129 patients (3.5%) switched back
      to atorvastatin following the TI. The average statin cost per claim in the 12
      month post-TI period was Dollars 70.93, 9.5% less than the average cost in the 12
      month pre-TI period (Dollars 78.40). The average cost per patient per year (PPPY)
      for statin laboratory tests (lipid panels, creatine kinase tests, and liver
      function tests) increased by 31.5% to Dollars 16.15 in the post-TI period
      compared with Dollars 12.28 PPPY in the pre-TI period, and medical office visit
      costs increased by 44.9% to Dollars 20.70 PPPY in the post-TI period compared
      with Dollars 14.29 PPPY in the preperiod. These increased costs related to the
      medical management of statin therapy were overwhelmed by an 11.7% reduction in
      statin drug costs, from Dollars 793.69 PPPY in the pre-TI period to Dollars
      701.01 PPPY in the post-TI period, resulting in a net 10.0% reduction for
      combined statin costs and related medical costs, from Dollars 820.27 PPPY in the
      pre-TI period to Dollars 737.87 in the post-TI period. After limiting the
      analysis to patients who did not convert from atorvastatin to pravastatin (which
      cost more than atorvastatin before the rebate) and controlling for the influence
      of potential confounders, statin expenditure decreased by 33% (P < 0.001).
      Multivariate models indicated no statistically significant differences in the
      costs related to the medical management of statin therapy after the TI compared
      with before the TI.

PMID- 16792440
TI  - PP-ICONS--another tool to help interpret asthma utilization studies.

PMID- 16792441
TI  - More evolution of the evidence in asthma disease management--SMART versus GOAL
      clinical trials debate the cost-benefit of LABA while the value of leukotriene
      modifiers, particularly montelukast, is uncertain.

PMID- 16792442
TI  - Comparison of rates of potentially inappropriate medication use according to the
      Zhan criteria for VA versus private sector medicare HMOs.
AB  - BACKGROUND: Inappropriate prescribing in the elderly is common, but rates across
      different health care systems and the impact of formulary restrictions are not
      well described. OBJECTIVE: To determine if rates of inappropriate medication use
      in the elderly differ between the Veterans Affairs (VA) health care system and
      the private sector Medicare health maintenance organization (HMO) patients.
      METHODS: A cross-sectional study design compared administrative pharmacy claims
      from 10 distinct geographic regions in the United States in the VA health care
      system and 10 analogous regions for patients enrolled in Medicare HMOs. The
      cohorts included 123,633 VA and 157,517 Medicare HMO patients aged 65 years and
      older. Inappropriate medication use was identified using the Zhan modification of
      the Beers criteria, which categorizes 33 potentially inappropriate drugs into 3
      major classifications: "always avoid," "rarely appropriate," and "some
      indications." Comparisons between the VA health care system and the private
      sector Medicare HMO were performed for overall differences and stratified by
      gender and age. The drug formulary status of the Zhan-criteria drugs was known
      for the VA health system but not for the Medicare HMO patients. RESULTS: Compared
      with private sector patients, VA patients were less likely to receive any
      inappropriate medication (21% vs. 29%, P <0.001), and in each classification:
      always avoid (2% vs. 5%, P <0.001), rarely appropriate (8% vs. 13%, P<0.001), and
      some indications (15% vs. 17%, P <0.001). The rate of inappropriate drug use was
      lower in the VA compared with the private sector for males (21% vs. 24%, P
      <0.001) and females (28% vs. 32%, P <0.001). Differences were consistent when
      stratified by age. CONCLUSION: Compared with private sector Medicare HMOs,
      elderly VA patients were less likely to receive medications defined by the Zhan
      criteria as potentially inappropriate. A restrictive formulary that excludes 12
      of the 33 Zhan criteria drugs may be a factor in the reduction of undesired
      prescribing patterns in elderly populations.

PMID- 16792443
TI  - Effect of a therapeutic maximum allowable cost (MAC) program on the cost and
      utilization of proton pump inhibitors in an employer-sponsored drug plan in
      Canada.
AB  - BACKGROUND: Therapeutic maximum allowable cost (MAC) is a managed care
      intervention that uses reference pricing in a therapeutic class or category of
      drugs or an indication (e.g., heartburn). Therapeutic MAC has not been studied in
      Canada or the United States. The proton pump inhibitor (PPI) rabeprazole was used
      as the reference drug in this therapeutic MAC program based on prices for PPIs in
      the province of Ontario. No PPI is available over the counter in Canada.
      OBJECTIVE: To evaluate the utilization and anticipated drug cost savings for PPIs
      in an employer-sponsored drug plan in Canada that implemented a therapeutic MAC
      program for PPIs. METHODS: An employer group with an average of 6,300 covered
      members, which adopted the MAC program for PPIs in June 2003, was compared with a
      comparison group comprising the book of business throughout Canada (approximately
      5 million lives) without a PPI MAC program (non-MAC group). Pharmacy claims for
      PPIs were identified using the first 6 characters of the generic product
      identifier (GPI 492700) for a 36-month period from June 1, 2002, through May 31,
      2005. The primary comparison was the year prior to the intervention (from June 1,
      2002, through May 31, 2003) and the first full year following the intervention
      (June 1, 2004, through May 31, 2005). Drug utilization was evaluated by comparing
      the market share of each of the PPIs for the 2 time periods and by the days of
      PPI therapy per patient per year (PPPY) and days of therapy per prescription
      (Rx). Drug cost was defined as the cost of the drug (ingredient cost), including
      allowable provincial pharmacy markup but excluding pharmacy dispense fee. Cost
      savings were calculated from the allowed drug cost per claim, allowed cost per
      day, and allowed cost PPPY. RESULTS: (All amounts are in Canadian dollars.) The
      MAC intervention group experienced an 11.7% reduction in the average cost per day
      of PPI drug therapy, from 2.14 US dollars in the preperiod to 1.89 US dollars in
      the postperiod, compared with a 3.7% reduction in the comparison group (2.16 US
      dollars vs. 2.08 US dollars). Utilization dropped by 11.9% in the intervention
      group, from 166.7 days of PPI drug therapy PPPY to 146.9 days PPPY, compared with
      an increase of 7.9% in the comparison group, from 136.1 days to 146.8 days PPPY.
      The combined effect of the decrease in drug cost per day and utilization was a
      22.1% reduction in allowed drug cost PPPY in the intervention (MAC) group (from
      357 US dollars to 278 US dollars PPPY) versus a 4.1% increase in the comparison
      group (from 293 US dollars to 305 US dollars PPPY). CONCLUSION: A MAC program for
      PPIs for one employer in Canada was associated with savings for the drug plan
      sponsor of approximately 8% in actual drug cost per day of therapy compared with
      the comparison group. Total savings after consideration of utilization was
      approximately 26% for the intervention group versus the comparison group.

PMID- 16792444
TI  - Cost reduction strategies used by elderly patients with chronic obstructive
      pulmonary disease to cope with a generic-only pharmacy benefit.
AB  - BACKGROUND: Generic-only pharmacy benefits may present more of a burden to
      patients with chronic disease conditions such as chronic obstructive pulmonary
      disease (COPD), where generic drug therapy choices are more limited. OBJECTIVE:
      To evaluate the strategies that elderly patients with COPD use to manage their
      out-of-pocket (OOP) prescription expenses in a generic-only pharmacy benefit
      compared with similar patients with a single-tier copayment or a 2-tier pharmacy
      benefit with coverage of brand formulary drugs. METHODS: Surveys were mailed to a
      sample of 3,000 Kaiser Permanente (California) patients (aged > or = 65 years)
      who had a diagnosis for COPD and received at least 1 prescription for a COPD
      related medication during 2003. The sample was stratified by type of pharmacy
      benefit: generic-only, single copayment tier, and 2 copayment tiers. The survey
      contained questions about strategies used to reduce OOP prescription expenses,
      such as stop taking a prescribed medication, purchase prescriptions out of the
      country, or discuss OOP prescription expenses with a physician. The likelihood of
      using specific strategies to reduce OOP prescription expenses was modeled using
      logistic regression. Covariates included social support, quality of life, smoking
      status, socioeconomic status, total prescription costs, and demographics.
      RESULTS: A total of 1,624 surveys were returned, for a 54% response rate. Results
      from logistic regressions indicate that COPD patients with a generic-only benefit
      are significantly more likely to report that they discussed their OOP costs with
      their physician (odds ratio [OR]=9.02; 95% confidence interval [CI], 6.15-
      13.22), purchased their medications from another country (OR=6.70; 95% CI, 3.17
      14.16) and reduced spending on food and clothing (OR=4.06; 95% CI, 2.70-6.12).
      They are also more likely to report that they had taken less than the prescribed
      amount of a regular medication (OR=1.70; 95% CI, 1.25-2.31) and that they stopped
      taking one or more of their regular medications (OR=1.77; CI, 1.27-2.47).
      Patients with low annual household incomes (<25,000 US dollars) were
      significantly more likely to discuss their OOP costs with their physician
      (OR=1.47; 95% CI, 1.08-2.00 ) and to reduce spending on food and clothing
      (OR=1.97; 95% CI, 1.42-2.73) than those with higher incomes. Approximately 15% of
      COPD patients obtained drug samples from their physicians as a method to reduce
      OOP costs, and there was no difference among the 3 groups in the prevalence of
      this cost management strategy. Overall, patients in the generic-only pharmacy
      benefit used an average of 3 methods to reduce OOP pharmacy costs compared with
      approximately 1.5 cost reduction methods used by patients in single-tier and 2
      tier copayment designs who had coverage of formulary brand as well as generic
      drugs. CONCLUSION: Elderly patients with COPD and a generic-drug-only pharmacy
      benefit are more likely to report using a variety of strategies to reduce their
      OOP costs compared with similar patients with single-tier copayment or 2-tier
      copayment pharmacy benefits. The most common strategy was discussing OOP costs
      with their physician, and use of this strategy was inversely related to household
      income. There was no difference in the proportion of COPD patients among the 3
      pharmacy benefit groups that used drug samples from their physicians as a means
      to reduce OOP costs.

PMID- 16792445
TI  - Evaluation of the performance of drug-drug interaction screening software in
      community and hospital pharmacies.
AB  - BACKGROUND: Computerized drug-drug interaction (DDI) screening is widely used to
      identify potentially harmful drug combinations in the inpatient and outpatient
      setting. OBJECTIVE: To evaluate the performance of drug-drug interaction (DDI)
      screening software in identifying select clinically significant DDIs in pharmacy
      computer systems in community and hospital pharmacies. METHODS: Ten community
      pharmacies and 10 hospital pharmacies in the Tucson metropolitan area were
      invited to participate in the study in 2004. To test the performance of each of
      the systems used by the pharmacies, 25 medications were used to create 6 mock
      patient profiles containing 37 drug-drug pairs, 16 of which are clinically
      meaningful DDIs that pose a potential risk to patient safety. Each profile was
      entered into the computer pharmacy system, and the system response in terms of
      the presence or absence of a DDI alert was recorded for each drug pair. The
      percentage of correct responses and the sensitivity, specificity, positive
      predictive value, and negative predictive value of each system to correctly
      classify each drug pair as a DDI or not was calculated. Summary statistics of
      these measures were calculated separately for community and hospital pharmacies.
      RESULTS: Eight community pharmacies and 5 hospital pharmacies in the Tucson
      metropolitan area agreed to participate in the study. The median sensitivity and
      median specificity for community pharmacies was 0.88 (range, 0.81-0.94) and 0.91
      (range, 0.67-1.00), respectively. For hospital pharmacies, the median sensitivity
      and median specificity was 0.38 (range, 0.15-0.94) and 0.95 (range, 0.81-0.95),
      respectively. CONCLUSION: Based on this convenience sample of 8 community
      pharmacies and 5 hospital pharmacies in 1 metropolitan area, the performance of
      community pharmacy computer systems in screening DDIs appears to have improved
      over the last several years compared with research published previously in 2001.
      However, significant variation remains in the performance of hospital pharmacy
      computer systems, even among systems manufactured by the same vendor. Future
      research should focus on improving the performance of these systems in accurately
      and precisely identifying DDIs with a high probability of resulting in true
      potential adverse effects on clinical outcomes and creating a low .noise. ratio
      associated with false-positive alerts.

PMID- 16792446
TI  - Experience with a clinical decision support system in community pharmacies to
      recommend narrow-spectrum antimicrobials, nonantimicrobial prescriptions, and OTC
      products to decrease broad-spectrum antimicrobial use.
AB  - BACKGROUND: Overuse of antibiotics increases the incidence of bacterial
      resistance and contributes avoidable costs to the health care system. OBJECTIVE:
      To determine the feasibility of a protocol-driven community pharmacy intervention
      that was designed to decrease broad-spectrum antimicrobial (BSA) use in patients
      with upper respiratory tract infections. METHODS: The intervention involved
      pharmacists who conducted guided interviews regarding patient symptoms in a
      cohort of patients with BSA prescription visiting 2 rural community pharmacies
      during peak respiratory illness season. A clinical decision support system was
      provided to aid in pharmacist diagnosis and assist in determining if the BSA
      therapy was appropriate. Upon patient consent, pharmacists attempted to contact
      primary care providers (PCPs) to confirm the diagnosis and recommend appropriate
      alternative therapy. RESULTS: There were 192 subjects with prescriptions for BSAs
      and symptoms of respiratory tract infection. Only 3% of the patients who were
      approached declined to discuss their symptoms and treatment with the pharmacist.
      A mean of 3 minutes was required to collect symptom and treatment information
      from the patients. However, when patients were asked if the pharmacist could
      contact their PCP to recommend alternative therapy, only 7% (n=4) of patients
      agreed to the intervention. The PCPs who were contacted by pharmacists were
      receptive to altering the BSA to first-line antimicrobial therapy such as
      amoxicillin or doxycycline. CONCLUSION: Despite a description of the importance
      of the intervention, more than 90% of patients prescribed a BSA declined to
      permit the community pharmacist to contact the prescriber to discuss first-line
      therapeutic alternatives. This experience in a pilot study to explore the
      feasibility of pharmacist intervention at the point of dispensing of a BSA made
      clear that a successful community pharmacy intervention to reduce BSA use would
      require an alternative method, perhaps via a collaborative practice protocol that
      does not require patient consent to make the drug substitution to first-line
      antibiotic therapy.

PMID- 16792447
TI  - Pharmacy management methods in Canada, including lower-cost therapy for
      heartburn.

PMID- 16792448
TI  - Heartburn in consumer-directed health care and the cost outcomes of therapeutic
      maximum allowable cost.

PMID- 16792449
TI  - Pharmacists should assume a larger role in overcoming the racial/ethnic barriers
      to breast cancer screening.

PMID- 16792450
TI  - Medicare Part D on the front line.

PMID- 16792451
TI  - Intestinal pseudo-obstruction: a diagnostic and therapeutic challenge for the
      21st century.

PMID- 16792452
TI  - A prospective study about functional and anatomic consequences of transanal
      endoscopic microsurgery.
AB  - INTRODUCTION: transanal endoscopic microsurgery (TEM) was developed in 1983 by
      Buess as a minimally invasive technique to manage rectal villous adenomas and
      early rectal adenocarcinomas. Many studies have been published worldwide about
      its excellent results in morbidity and recidive rate, but there are few studies
      addressing functional results. The objective of this study is to analyze the
      effect of this technique in the anal anatomy and compare with the manometric
      results. MATERIAL AND METHODS: we devised a prospective study of 40 patients. 39%
      female, 61% male. All of them filled an incontinence questionnaire (Pescatori
      scale) and endoanal ultrasonography and manometry was carried out preoperatively,
      third month postoperative and at sixth month only if incontinence appeared.
      RESULTS: 32 patients (80%) had villous adenomas and 8 patients (20%) had
      adenocarcinomas (uT1). Three patients complained of flatus incontinence at 3rd
      postoperative month that disappeared with normal continence at 6th month.
      Anorectal manometric values: mean anal resting pressure (ARP) decreased at 3rd
      month (from 87.2 mmHg to 70.1 mmHg), as it was for maximal squeeze pressure (MSP)
      from 152.5 mmHg preoperatively to 142.2 mmHg at 3rd month. Ultrasonography
      demonstrated internal anal sphincter (IAS) rupture in 3 patients, with a full
      integrity of the external anal sphincter in all patients. CONCLUSIONS: during
      TEM, a significant anal dilatation occurs, because of rectoscopy (40 mm wide),
      what can produce a rupture of IAS, with the consequent decreasing in ARP, and a
      dilatation without rupture of external sphincter what produces a decreasing of
      MSP. The fall of anal pressures had minima clinical repercussion when sphincter
      is intact, but when IAS is broken a temporal incontinence develops.

PMID- 16792453
TI  - Prevalence of Helicobacter pylori infection in the general adult population of
      the province of Ourense.
AB  - OBJECTIVES: to determine the prevalence of Helicobacter pylori infection in the
      general adult population of the province of Ourense. MATERIAL AND METHODS: a
      cross-sectional study was carried out with a randomly selected populational
      sample. The diagnosis of Helicobacter pylori infection was reached using the 13C
      urea breath test. RESULTS: three hundred and eighty-three subjects were studied,
      with a prevalence rate of 69.1% (95% CI: 61.7-75.1%); 69.8% (95% CI: 63.2-76.6%)
      in males and 68.4% (95% CI: 61.5-75.4%) in females (difference not statistically
      significant). Prevalence increases with age up to a maximum of 88.4% in the 45-54
      years age group, and decreases thereafter to a rate of 57.1% in individuals over
      the age of 84 years. CONCLUSION: this study reveals that the prevalence rate of
      Helicobacter pylori infection is high in the general adult population of the
      province of Ourense. It increases with age until it peaks in the group of middle
      aged individuals and is similar in both sexes.

PMID- 16792455
TI  - Spanish scientific output on Helicobacter pylori. A study through Medline.
AB  - OBJECTIVES: to analyze scientific output from Spanish hospitals in relation to
      Helicobacter pylori infection. METHODS: papers collected from the Medline
      database between January 1988 and December 2003 were selected. Our search
      strategy was: "Helicobacter pylori" [MeSH] AND ((Spain [AD] OR Espana [AD] OR
      Spanien [AD] OR Espagne [AD] OR Espanha [AD]) OR (Spanish [LA]) OR Spain). The
      following was analyzed: geographic area, Spanish or foreign publication, topic,
      and year of publication. Output and impact bibliometric markers were evaluated.
      RESULTS: in all, 691 papers were identified, of which 241 were excluded. Number
      of papers went from 2 in 1988 to 47 in 2002 and 13 in 2003. There were more
      reports in Spanish versus foreign journals (58 vs. 42%). In the first 5 years the
      areas with greater output were associated with diagnosis and microbiology (33 and
      20%), whereas therapy was the predominating subject during the last 5 years
      (27%). Original papers were most common among publications (69%). Hospitals with
      highest output included La Princesa (24%) and Ramon y Cajal (17.6%) in Madrid,
      and Parc Tauli in Barcelona (6.4%). Mean impact factor progressively increased
      from 1.826 in 1988 to 2.142 in 2002 and 2.493 in 2003. CONCLUSIONS: the
      production and impact of documents published by Spanish scientists regarding H.
      pylori infection considerably increased during the past two decades.

PMID- 16792454
TI  - A comparison of two different dosages of somatostatin combined with sclerotherapy
      for the treatment of acute esophageal variceal bleeding: a prospective randomized
      trial.
AB  - BACKGROUND: the association of somatostatin (SMT) with endoscopic therapy in
      patients with cirrhosis and variceal bleeding significantly improves the control
      of the bleeding episode, and hemodynamic data have shown that a dosage of 500
      mg/h allows a more marked reduction of portal pressure versus the usual dosage of
      250 mg/h. AIM: to assess if the 500 mg/h dosage is associated with an improved
      outcome. METHODS: sixty-two patients with variceal bleeding were included in the
      study. Patients were randomized to receive the usual dosage of SMT (group I: 250
      mg/h), or a double dosage (group II: 500 mg/h), together with emergency
      endoscopic sclerotherapy. RESULTS: the control of the bleeding episode was
      similar in both groups of patients. Early rebleeding was less frequent in
      patients receiving double vs. single dosage of SMT (p = 0.06). When considering
      patients with advanced liver disease (Child-Pugh B or C) early rebleeding was
      significantly less frequent in patients receiving the 500 mg/h dose of SMT (39
      vs. 13%, p = 0.03). CONCLUSIONS: the perfusion of higher doses of SMT (500 mg/h)
      in association with emergency sclerotherapy in patients with cirrhosis and
      esophageal hemorrhage significantly decreases the rate of early rebleeding in
      patients with more advanced stages of liver disease.

PMID- 16792456
TI  - Biologic therapies for chronic inflammatory bowel disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) make up the so-called chronic
      inflammatory bowel disease (IBD). Advances in the understanding of IBD
      pathophysiologic mechanisms in the last few years have allowed the development of
      novel therapies such as biologic therapies, which at least theoretically
      represent a more specific management of this disease with fewer side effects.
      Currently, the only effective and widely accepted biologic therapy for the
      treatment of intraluminal, fistulizing CD, both for remission induction and
      maintenance, is infliximab. The role of other monoclonal antibodies such as
      adalimumab is not clearly established. It could be deemed an alternative for
      patients with allergic reactions to infliximab, and for those with lost response
      because of anti-infliximab antibody development. However, relevant issues such as
      dosage and administration regimen remain to be established. Anti-integrin a4
      therapies, despite encouraging results in phase-3 studies, are still unavailable,
      as their marketing authorization was held back in view of a number of reports
      regarding progressive multifocal leukoencephalopathy cases. Immunostimulating
      therapy may be highly relevant in the near future, as it represents a novel
      strategy against disease with the inclusion of granulocyte-monocyte colony
      stimulating factors.Regarding ulcerative colitis, results from the ACT-1 and ACT
      2 studies showed that infliximab is also useful for the management of serious UC
      flare-ups not responding to standard treatment, which will lead to a revision of
      therapeutic algorithms, where this drug should be given preference before
      intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs
      (vilisilizumab), T-cell inhibiting therapies, and epithelial repair and healing
      stimulating factors will be established.

PMID- 16792457
TI  - Chronic primary intestinal pseudo-obstruction from visceral myopathy.
AB  - Chronic intestinal pseudo-obstruction is an uncommon syndrome characterized by
      relapsing episodes suggesting intestinal obstruction during which no mechanical
      causes are identified to account for symptoms. Etiologic factors may be manifold.
      Among them a number of neurologic conditions, gastrointestinal smooth muscle
      myopathies, endocrino-metabolic and autoimmune diseases, and the use of selected
      drugs stand out. We report a case of chronic intestinal pseudo-obstruction
      originating in a sporadic, primary intestinal myopathy that corresponds to no
      type thus far described. A histological study of the intestinal wall showed
      disrupted muscle bundles and the presence of interstitial edema. Myocytes had
      severe degenerative changes, and no alterations were seen in submucosal and
      myenteric plexus neurons. The activity of enzyme complexes in the mitochondrial
      respiratory chain, and of thymidine phosphorylase was normal. No mitochondrial
      DNA changes were seen.

PMID- 16792458
TI  - Intramural rupture of the esophagus: clinical presentation and outcome.

PMID- 16792459
TI  - Multiple bile-duct hamartomas (Von Meyemburg complexes).

PMID- 16792460
TI  - [Dormia baskets impacted in the bile duct after endoscopic retrograde
      cholangiopancreatography].

PMID- 16792461
TI  - [Mucinous adenocarcinoma on chronic perianal fistula treated by neoadjuvant QT-RT
      neoadyuvante and laparoscopic abdomino-perineal resection].

PMID- 16792462
TI  - Tolerance to acute ischemia in adult male and female spontaneously hypertensive
      rats.
AB  - Clinical and experimental studies have repeatedly indicated that overloaded
      hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the
      present study was to answer the question whether the degree of tolerance to
      oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex
      dependent. For this purpose, adult SHR and their normotensive control Wistar
      Kyoto (WKY) rats were used. The isolated hearts were perfused according to
      Langendorff at constant pressure (proportionally adjusted to the blood pressure
      in vivo). Recovery of contractile parameters (left ventricular systolic,
      diastolic and developed pressure as well as the peak rate of developed pressure)
      was measured during reperfusion after 20 min of global no-flow ischemia in 5 min
      intervals. Mean arterial blood pressure was measured by direct puncture of
      carotid artery under light ether anesthesia in a separate group of animals. The
      degree of hypertension was comparable in both sexes of SHR. The recovery of
      contractile functions in SHR males and females was significantly lower than in
      WKY rats during the whole investigated period. There was no sex difference in the
      recovery of WKY animals; on the other hand, the recovery was significantly better
      in SHR females than in SHR males. It may be concluded that the hearts of female
      SHR are more resistant to ischemia/reperfusion injury as compared with male SHR.
      This fact could have important clinical implications for the treatment of
      cardiovascular disease in women.

PMID- 16792463
TI  - Genetic susceptibility to type 1 diabetes mellitus in humans.
AB  - Type 1 diabetes mellitus (DM 1A) is an autoimmune disease belonging to the most
      frequent chronic diseases of the childhood and young adults. DM 1A results from
      immune-mediated destruction of the insulin-producing beta cells of the pancreas.
      It is a genetically determined disease and many genes or genetic regions were
      found to be associated with its induction. In addition to the insulin-dependent
      diabetes mellitus 1 (IDDM1) gene, which marks the HLA region, and IDDM2 which
      marks the insulin gene, significant associations of DM 1A to other IDMM genes or
      genetic regions we reported. We shortly review recent achievements in the field,
      and the state of current knowledge.

PMID- 16792464
TI  - Diurnal variation of 6beta-hydroxycortisol in cardiac patients.
AB  - The 24-hour urinary excretion of 6-beta-hydroxycortisol (6beta-OHC) and the
      urinary ratio of 6beta- hydroxycortisol/cortisol (6beta-OHC/UFC) have been
      proposed as noninvasive probes for human cytochrome P450 3A4 isoform (CYP3A4). In
      this study, we evaluated within- and between-day variability of 6beta-OHC
      excretion and 6beta-OHC/UFC ratio in nine Caucasian men with cardiac disease.
      Each study participant was asked to collect 24-hour urine specimens during four
      consecutive days in five standardized time intervals. Concentrations of UFC and
      6beta-OHC were determined by immunoassay and the high-performance liquid
      chromatographic (HPLC) method, respectively. The HPLC method was accurate and
      precise, as indicated by the recovery rate of 96.5-103.3 % and less than 5.2 %
      and 6.3 % of the coefficient of variation for within-run and between-run assay,
      respectively. In patients, diurnal variations in UFC and 6beta-OHC excretion were
      parallel. Consequently, 6beta-OHC/UFC ratio remained stable during the day. Both,
      6beta-OHC excretion and 6beta-OHC/UFC ratio showed significant relationship
      between 24-hour value and values measured in corresponding collection periods
      with best correlations obtained from night interval (22.00-06.00, r = 0.86-0.91).
      These results indicated that urinary 6beta-OHC excretion and 6beta-OHC/UFC ratio
      measured in overnight/morning urine could precisely reflect 24-hour values even
      in severely ill patients. In addition, a simple and sensitive HPLC method was
      described for determination of 6beta-OHC in urine.

PMID- 16792465
TI  - Distribution and interrelationship of ubiquitin proteasome pathway component
      activities and ubiquitin pools in various porcine tissues.
AB  - The ubiquitin-proteasome pathway fulfills major biological functions, but its
      physiologic tissue distribution and the interrelationship between pathway
      component activities and ubiquitin pools are unknown. Therefore, we analyzed free
      and conjugated ubiquitin, ubiquitin-protein ligation rates (UbPL) and
      chymotryptic- and tryptic-like proteasome peptidase activities in porcine
      skeletal muscle, heart, lung, liver, spleen and kidney (n=5 each). There were
      considerable differences between tissues (p<0.05 for all parameters). Lung and
      spleen showed high levels of free and conjugated ubiquitin and high UbPL.
      Proteasome activities were highest in kidney and heart. There were linear
      relationships between tryptic-like and chymotryptic-like proteasome peptidase
      activities (r(2) = 0.624, p<0.001) and between free and conjugated ubiquitin
      tissue levels (r(2) = 0.623, p<0.001). Tissue levels of free and conjugated
      ubiquitin correlated linear with UbPL (p<0.005), but they were not correlated
      with proteasome peptidase activities. The results suggest that tissue ubiquitin
      pools are tightly regulated and indicate a constant proportion of conjugated
      ubiquitin. They further support the hypothesis that ubiquitin-protein ligase
      systems, and probably deubiquitylating enzymes, are key regulators of ubiquitin
      homeostasis. The detected differences are suggestive of tissue-specific roles of
      ubiquitin-proteasome pathway components. Besides the known importance of the
      ubiquitin proteasome pathway in heart, kidney and the immune system, the results
      suggest the lung as another organ in which ubiquitin proteasome pathway
      components may also significantly contribute to disease processes.

PMID- 16792466
TI  - Early rehabilitation model shows positive effects on neural degeneration and
      recovery from neuromotor deficits following traumatic brain injury.
AB  - This study used an experimental early rehabilitation model combining an enriched
      environment, multisensory (visual, acoustic and olfactory) stimulation and motor
      training after traumatic brain injury (via fluid-percussion model) to simulate
      early multisensory rehabilitation. This therapy will be used by brain injured
      patients to improve neural plasticity and to restore brain integration functions.
      Motor dysfunction was evaluated using a composite neuroscore test. Direct
      structural effects of traumatic brain injury were examined using Fluoro-Jade
      staining, which allows identification of degenerating neural cell bodies and
      processes. Animals in the rehabilitation model group performed significantly
      better when tested for neuromotor function than the animals in standard housing
      in the 7-day and 15-day interval after injury (7d: p=0.005; 15d: p<0.05).
      Statistical analysis revealed significantly lower numbers of Fluoro-Jade positive
      cells (degenerating neurons) in the rehabilitation model group (n=5: mean 13.4)
      compared to the standard housing group (n=6: mean 123.8) (p<0.005). It appears
      that the housing of animals in the rehabilitation model led to a clear functional
      increase in neuromotor functions and to reduced neural loss compared with the
      animal group in standard housing.

PMID- 16792467
TI  - Influence of load changes on tricuspid inflow.
AB  - In healthy subjects, the right ventricular filling pattern estimated from
      tricuspid valve inflow is highly load-dependent. This can be clearly demonstrated
      by changes of Doppler inflow tracings recorded during tidal breathing at rest.
      The aim of our study was to test the magnitude of tricuspid inflow changes during
      more pronounced load changes induced by specific maneuvers. In 31 apparently
      healthy subjects (16 men and 15 women, mean age 36+/-16 years) we recorded pulsed
      Doppler tracings of tricuspid inflow during forced inspiration, elevation of
      lower extremities (increased preload) and handgrip exercise (increased
      afterload). The obtained values were compared with end-expiratory phase of tidal
      breathing at rest. We found a significantly larger increase in the early and late
      filling velocities (for E and A p<0.001) under the conditions of increasing
      preload (elevation of legs) and less pronounced, but still significant changes
      with isometric exercise (for E p<0.001 and for A p<0.01). We conclude that the
      right ventricular filling pattern in healthy humans is highly load-sensitive and
      for this reason the effect of any intervention (e.g. pharmacological) must be
      studied under strict and well-defined resting conditions.

PMID- 16792468
TI  - Activity of paraoxonase 1 and lipid profile in healthy children.
AB  - Paraoxonase 1 (PON1) seems to have a relevant role in detoxifying processes and
      in atherosclerosis. The aim of this study was to determine PON1 activity, the
      total antioxidant capacity, as well as entire lipid profile in children for
      screening of possible risk of atherosclerosis development. Serum PON1
      arylesterase/paraoxonase activities were determined spectrophotometrically. The
      total antioxidant capacity of the serum was measured by TEAC method. Parameters
      of lipid profile were analyzed by routine laboratory methods. It has been shown
      that PON1 arylesterase/ paraoxonase activities were very similar to values found
      in adults. In children, no significant correlation between PON1 arylesterase
      activity and HDL was observed. PON1 paraoxonase activity correlated only with
      atherogenic index. PON1 arylesterase activity was significantly higher in girls
      than in boys. The antioxidant capacity was inversely related to the body mass
      index. In this study, PON1 activity was determined in healthy children aged 11 to
      12 years and we found a similarity in PON1 activities of children and adults.
      Moreover, the results of our study support the hypothesis that higher body weight
      of children may contribute to a greater risk for development of atherosclerosis
      in which oxidative stress plays a role.

PMID- 16792469
TI  - Chronic oral administration of beta-adrenoceptor agonist clenbuterol affects
      myosin heavy chain (MHC) expression in adult mouse heart.
AB  - The aim of this study was to analyze the effects of chronic administration of the
      beta-adrenoceptor agonist clenbuterol (2 mg/kg body weight/day for a period of 30
      days) on the major contractile protein (myosin) in the left ventricular muscle of
      the adult mouse heart. Separation of myosin heavy chain (MHC) isoforms on 7.5 %
      glycerol SDS-PAGE and subsequent quantification of the gels by laser densitometry
      showed a 6.5-fold increase in the beta-isoform of MHC in the clenbuterol-treated
      group. The alpha : beta ratio of these two isoforms in the control group was
      98.16+/-0.14 %: 1.83+/-0.14 %, whereas in the treated group it was 88.05+/-1.15 %
      : 11.95+/-1.15 %. Actomyosin ATPase activity assay demonstrated a significant (20
      %) decline in ATPase activity of the tissue in the beta-agonist-treated group.
      These results suggest that chronic clenbuterol treatment is capable to induced
      the transformation of MHC isoforms increasing the slow beta-MHC isoform, which
      may contribute to the altered contractile mechanics of clenbuterol-treated
      hearts.

PMID- 16792470
TI  - Effect of an increase in coronary perfusion on transmural ventricular
      repolarization.
AB  - The effect of increased coronary flow on transmural ventricular repolarization
      was investigated in six pentobabital-anesthetized sheep. Fresh blood at 10 ml/min
      was injected into the left circumflex coronary artery (LCX) in addition to the
      normal coronary flow. Unipolar electrocardiograms were simultaneously registered
      from epicardium, mid-myocardium and endocardium with fine plunge needles.
      Activation-recovery interval (ARI) was measured from the unipolar
      electrocardiograms and was used for estimating the ventricular repolarization
      duration. It was found that intracoronary blood injection (n=3) prolonged ARI in
      the epicardium, mid-myocardium and endocardium by an average of 34 +/- 16, 28 +/-
      18 and 25 +/- 13 ms, respectively (p<0.01). Pretreatment with nitro-L-arginine
      (n=3), a nitric synthase inhibitor, diminished the flow-induced ARI prolongation
      across the ventricular wall. In conclusion, an increase in coronary flow
      lengthens the duration of transmural ventricular repolarization. These effects
      appear to be mediated by nitric oxide from the coronary endothelium.

PMID- 16792471
TI  - Different sensitivity of miniature endplate currents of the rat extensor
      digitorum longus, soleus and diaphragm muscles to a novel acetylcholinesterase
      inhibitor C-547.
AB  - A novel derivative of 6-methyluracil, C-547, increased the amplitude and
      prolonged the duration of miniature endplate currents (MEPCs) which is typical
      for acetylcholinesterase inhibition. In the soleus and extensor digitorum longus
      significant potentiation was detected at nanomolar concentrations. In contrast,
      in the diaphragm muscle, the increase in the amplitudes of the MEPCs and the
      decay time constant appeared only when the concentration of C-547 was elevated to
      1 x 10(-7) M. Possible consequences for the exploitation of this drug, which can
      selectively inhibit AChE in particular synapses, are discussed.

PMID- 16792472
TI  - Markers of acute stress in pigs.
AB  - This study explores the biological validation of markers of acute stress in pigs
      subjected to transportation for slaughter. The stress markers selected for
      monitoring were neopterin and cortisol. Their levels in pig serum were measured
      for two porcine stress syndrome genotypes, NN and Nn, after a 30-min transport to
      a slaughterhouse. Blood samples were withdrawn before transport (control group)
      and immediately after the animals' arrival (experimental group). The values of
      neopterin and cortisol measured before the transport were 5.60+/-1.65 nmol/l and
      273.54+/-66.17 nmol/l respectively. After the transfer, the concentration of
      cortisol rose significantly compared to the control (355.69+/-85.13 nmol/l,
      p<0.01). Neopterin concentrations in the serum (8.25+/-1.60 nmol/l) were also
      significantly higher (p<0.01) after transportation. The elevated concentrations
      of both analytes were found to be independent of the genotype. These results
      document the stimulation of the endocrine system and the immune system that
      develops in animals undergoing transportation for slaughter.

PMID- 16792473
TI  - Leptin inhibits gastric emptying in rats: role of CCK receptors and vagal
      afferent fibers.
AB  - Leptin regulates energy homeostasis and body weight by balancing energy intake
      and expenditure. It was recently reported that leptin, released into the gut
      lumen during the cephalic phase of gastric secretion, is capable of initiating
      intestinal nutrient absorption. Vagal afferent neurons also express receptors for
      both CCK and leptin, which are believed to interact in controlling food intake.
      The present study was undertaken to investigate the central and peripheral
      effects of leptin on gastric emptying rate. Under anesthesia, male Sprague-Dawley
      rats (250-300 g) were fitted with gastric Gregory cannulas (n=12) and some had
      additional cerebroventricular cannulas inserted into their right lateral
      ventricles. Following recovery, the rate of gastric emptying of saline (300
      mOsm/kg H(2)O) was determined after instillation into the gastric fistula (3 ml,
      37 degrees C, containing phenol red, 60 mg/l as a non-absorbable dilution
      marker). Gastric emptying rate was determined from the volume and phenol red
      concentrations recovered after 5 min. Leptin, injected intraperitoneally (i.p.;
      10, 30, 60, 100 microg/kg) or intracerebroventricularly (i.c.v.; 5, 15
      microg/rat) 15 min before the emptying, delayed gastric emptying rate of saline
      at the dose of 30 microg/kg or 15 microg/rat (p<0.001). When CCK(1) receptor
      blocker L-364,718 (1 mg/kg, i.p.), CCK(2) receptor blocker L-365,260 (1 mg/kg,
      ip) or adrenergic ganglion blocker bretylium tosylate (15 mg/kg, i.p.) was
      administered 15 min before ip leptin (30 microg/kg) injections, leptin-induced
      delay in gastric emptying was abolished only by the CCK(1) receptor blocker
      (p<0.001). However, the inhibitory effect of central leptin on gastric emptying
      was reversed by adrenergic blockade, but not by either CCK antagonists. Our
      results demonstrated that leptin delays gastric emptying. The peripheral effect
      of leptin on gastric motility appears to be mediated by CCK(1) receptors,
      suggesting the release of CCK and the involvement of vagal afferent fibers. On
      the other hand, the central effect of leptin on gastric emptying is likely to be
      mediated by adrenergic neurons. These results indicate the existence of a
      functional interaction between leptin and CCK receptors leading to inhibition of
      gastric emptying and short-term suppression of food intake, providing an
      additional feedback control in producing satiety.

PMID- 16792474
TI  - Effect of combined therapy with hyperbaric oxygen and antioxidant on infarct
      volume after permanent focal cerebral ischemia.
AB  - The aim of the present study was to evaluate the efficiency of combination of
      hyperbaric oxygen (HBO) and an antioxidant on permanent focal cerebral ischemia.
      Male Wistar rats underwent permanent middle cerebral artery occlusion (MCAO).
      Then, animals were randomly assigned to one of four groups: the control group
      (n=9) received no treatment, HBO group (n=9) was treated for 90 min at 2.5
      absolute atmosphere for 3 days, the U-74389G group (n=8) received single U-74389G
      injection (3 mg/kg), the HBO + U-74389G group (n=8) received both HBO and U
      74389G treatments. Treatments were initiated within the first 10 min after MCAO.
      After 3 days, the infarct volumes in rat brains were measured. The infarct ratios
      were 25.6+/-6.5 % for the control group, 21.9+/-6.4 % for the HBO group, 15.7+/
      5.7 % for U-74389G group and 12.5+/-3.8 % for HBO + U74389G group. The infarct
      volumes were significantly reduced in rats treated with U-74389G (p<0.05) and
      combination therapy (p<0.05). HBO failed to reduce infarct volume significantly.
      We concluded that 1) U-74389G is more beneficial than HBO on permanent MCAO in
      rats, and 2) a combined therapy failed to significantly improve infarct volume
      more than either single treatment.

PMID- 16792475
TI  - Cytokine profile of human septic shock serum inducing cardiomyocyte contractile
      dysfunction.
AB  - This study was designed to measure nitrite/nitrate and cytokine levels of serum
      obtained from septic shock patients and to describe potential depressant effects
      of human septic serum on rat cardiomyocytes. Serum was prepared from 10 non
      septic patients and 10 patients with documented septic shock. Adult rat
      ventricular myocytes were exposed to 20 % serum in the medium. Cardiomyocyte
      contractility was assessed by measuring shortening fraction and shortening
      velocity. Serum levels of nitrite/nitrate, a marker of nitric oxide final
      metabolites, and cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, 6, 10, 8 and 12p70) were measured. Compared with serum from non-septic
      patients, serum of septic shock patients induced rapid reduction of the extent
      and velocity of shortening in isolated cardiomyocytes. Nitrite/nitrate, TNF
      alpha, IL-1beta and IL-12p70 concentrations of tested serum for cardiomyocyte
      studies were not increased in septic serum compared with controls. In contrast,
      septic serum that induced a depression of in vitro contractility, had increased
      levels of IL-6, IL-8 and IL-10. We can conclude that the depression of in vitro
      contractility induced by septic serum is not directly dependent on elevated
      levels of nitric oxide metabolites, TNF-alpha or IL-1beta. Our results support
      the view that other cytokines, including IL-6, IL-8 and IL-10, are potent
      circulating mediators of myocardial depression in cardiomyocytes.

PMID- 16792476
TI  - The effect of interleukin-17 on hematopoietic cells and cytokine release in mouse
      spleen.
AB  - To evaluate whether the response of hematopoietic cells to interleukin-17 (IL-17)
      depends on the tissue microenvironment in which hematopoiesis occurs, the
      influence of recombinant mouse IL-17 on spleen hematopoietic cells and cytokine
      release was assessed in normal mice in vitro and in vivo. In vitro, IL-17 did not
      significantly affect the growth of granulocyte-macrophage (CFU-GM) and erythroid
      (BFU-E and CFU-E) derived colonies. A single injection of IL-17 in vivo exhibited
      stimulatory effects on hematopoietic cells from both granulocytic and erythroid
      lineages. The increased number of metamyelocytes 48 h after treatment imply to
      the IL-17-induced stimulation of granulopoiesis. The number of BFU-E was
      increased at 24 h, while the number of CFU-E increased 6 h and 24 h after
      treatment. Since the same treatment in the bone marrow decreased the number of
      CFU-E, it may be concluded that the local microenvironment plays an important
      role in IL-17-mediated effects on CFU-E. IL-17 increased the release of IL-6 both
      in vitro and in vivo, but showed tendency to suppress the constitutive secretion
      of IL-10 by spleen cells. Our results suggest the complexity of target cell
      response and interplay of secondary induced cytokines by IL-17 in different
      hematopoietic organs.

PMID- 16792477
TI  - WHO issues draft protocol for containing and influenza pandemic.

PMID- 16792478
TI  - Interview with Mark Klempner, MD, principal investigator, National Emerging
      Infectious Diseases Laboratories, and associate provost for research, Boston
      University School of Medicine.

PMID- 16792479
TI  - Billions for biodefense: Federal Agency biodefense funding, FY2006-FY2007.
AB  - Since 2001, the United States government has spent substantial resources on
      preparing the nation against a bioterrorist attack. Earlier articles in this
      series analyzed the civilian biodefense funding by the federal government from
      fiscal years 2001 through 2006. This article updates those figures with budgeted
      amounts for fiscal year 2007, specifically analyzing the budgets and allocations
      for biodefense at the Department of Health and Human Services, the Department of
      Homeland Security, the Department of Agriculture, the Environmental Protection
      Agency, the Department of State, and the National Science Foundation.

PMID- 16792480
TI  - Meta-leadership and national emergency preparedness: A model to build government
      connectivity.
AB  - Effective emergency preparedness and response requires leadership that can
      accomplish perceptive coordination and communication amongst diverse agencies and
      sectors. Nevertheless, operating within their specified scope of authority,
      preparedness leaders in characteristic bureaucratic fashion often serve to
      bolster the profile and import of their own organization, thereby creating a silo
      effect that interferes with effective systemwide planning and response. This
      article describes a strategy to overcome traditional silo thinking: "meta
      leadership," overarching leadership that intentionally connects the purposes and
      work of different organizations or organizational units. Thinking and operating
      beyond their immediate scope of authority, meta-leaders provide guidance,
      direction, and momentum across organizational lines that develop into a shared
      course of action and a commonality of purpose among people and agencies that are
      doing what may appear to be very different work. Meta-leaders are able to
      imaginatively and effectively leverage system assets, information, and
      capacities, a particularly critical function for organizations with emergency
      preparedness responsibilities that are constrained by ingrained bureaucratic
      patterns of behavior.

PMID- 16792481
TI  - Systemic collapse: Medical care in the aftermath of Hurricane Katrina.
AB  - This article describes and analyzes key aspects of the medical response to
      Hurricane Katrina in New Orleans. It is based on interviews with individuals
      involved in the response and on analysis of published reports and news articles.
      Findings include: (1) federal, state, and local disaster plans did not include
      provisions for keeping hospitals functioning during a large-scale emergency; (2)
      the National Disaster Medical System (NDMS) was ill-prepared for providing
      medical care to patients who needed it; (3) there was no coordinated system for
      recruiting, deploying, and managing volunteers; and (4) many Gulf Coast residents
      were separated from their medical records. The article makes recommendations for
      improvement.

PMID- 16792482
TI  - The biological threat to U.S. water supplies: Toward a national water security
      policy.
AB  - In addition to providing potable drinking water, U.S. water systems are critical
      to the maintenance of many vital public services, such as fire suppression and
      power generation. Disruption of these systems would produce severe public health
      and safety risks, as well as considerable economic losses. Thus, water systems
      have been designated as critical to national security by the U.S. government.
      Previous outbreaks of waterborne disease have demonstrated the vulnerability of
      both the water supply and the public's health to biological contamination of
      drinking water. Such experiences suggest that a biological attack, or even a
      credible threat of an attack, on water infrastructure could seriously jeopardize
      the public's health, its confidence, and the economic vitality of a community.
      Despite these recognized vulnerabilities, protecting water supplies from a
      deliberate biological attack has not been sufficiently addressed. Action in this
      area has suffered from a lack of scientific understanding of the true
      vulnerability of water supplies to intentional contamination with bioweapons,
      insufficient tools for detecting biological agents, and a lack of funds to
      implement security improvements. Much of what is needed to address the
      vulnerability of the national water supply falls outside the influence of
      individual utilities. This includes developing a national research agenda to
      appropriately identify and characterize waterborne threats and making funds
      available to implement security improvements.

PMID- 16792483
TI  - Regulating biorisks: Developing a coherent policy logic (part I).
AB  - This is the first of two articles empirically detailing the working practices of
      regulators who are charged with overseeing biological research. Specifically, it
      considers how regulators from the Biological Agents Unit of the UK Health and
      Safety Executive review notifications and applications, carry out inspections of
      research centres, and enforce the law once breaches are uncovered. This first
      article focuses on the Unit's working practices before 9/11, and the second,
      forthcoming article focuses on the Unit's working practices after 9/11. I argue
      that an understanding of the implementation processes--that is, the strategies
      adopted by regulatory agencies and the styles employed by agency regulators in
      their interactions with those regulated--is critical to developing a coherent
      policy logic for the developing regulatory regime around biorisks.

PMID- 16792484
TI  - Removing barriers to global pandemic influenza vaccination.
AB  - This article clarifies the regulatory issues surrounding influenza pandemic
      vaccine for the larger policy community and describes the need for regulatory
      harmonization. Vaccination would save lives in an influenza pandemic, but a lack
      of global manufacturing capacity will leave most of the world without access to
      vaccine. Capacity can be expanded if governments harmonize their regulatory
      policies. This article details the regulatory approaches taken by the United
      States, the European Union, and Japan for pandemic vaccine development, three
      regions that produce the majority of the world's seasonal influenza vaccine. They
      should quickly converge on regulatory requirements, intellectual property
      considerations, the use of recombinant DNA techniques for vaccine production, and
      technical issues about the composition of pandemic vaccine.

PMID- 16792485
TI  - Getting medicine to millions: New strategies for mass distribution.
AB  - This article examines the feasibility of allowing private industries such as
      grocery stores, wholesale clubs, and community immunizers to partner with public
      health authorities for the mass distribution of vaccines or antibiotics. Retail
      grocery and wholesale stores already have experience with annual influenza
      vaccination and may be a resource in a public health emergency, including a
      bioterrorist attack. This analysis suggests that retail store executives are
      willing to work with public health authorities to plan for and respond to public
      health emergencies.

PMID- 16792486
TI  - Positive-pressure ventilation equipment for mass casualty respiratory failure.
AB  - In the event of an influenza pandemic, patients with severe acute respiratory
      failure (ARF) due to influenza will require positive-pressure ventilation (PPV)
      in order to survive. In countries with widely available critical care services,
      PPV is delivered almost exclusively through use of full-feature mechanical
      ventilators in intensive care units (ICUs) or specialized hospital wards. But the
      supply of these ventilators is limited even during the normal course of hospital
      functioning. Purchasing and maintaining additional full-feature mechanical
      ventilators to be held in reserve and used only during mass casualty events is
      too expensive to allow the stockpiling of such equipment. Consequently, planning
      and preparedness efforts to respond to a severe influenza pandemic have
      stimulated consideration of limited-feature, less-expensive ventilation devices
      to augment traditional PPV capacity. This article offers guidance to authorities
      charged with preparing for mass casualty PPV in deciding which PPV equipment
      would be adequate for ventilating patients for days, weeks, or even months during
      a medical catastrophe.

PMID- 16792487
TI  - Avoiding the biological security dilemma: A response to Petro and Carus.

PMID- 16792489
TI  - Comments from the Center for Biosecurity of UPMC on proposed revisions to federal
      quarantine rules.
AB  - On November 30, 2005, the U.S. Centers for Disease Control and Prevention (CDC)
      proposed changes to federal quarantine regulations (42 CFR Parts 70 and 71). As
      stated in the proposed rules, the intent of changes is "to clarify and strengthen
      existing procedures to enable CDC to respond more effectively to current and
      potential communicable disease threats." Parts 70 and 71 of 42 CFR authorize the
      Secretary of the Department of Health and Human Services (HHS) to make and
      enforce regulations "as in his judgement are necessary to prevent the
      introduction, transmission, and spread of communicable diseases" from foreign
      countries (Part 71) and between states (Part 70). The Center for Biosecurity of
      UPMC reviewed the proposed revisions to the quarantine regulations and submitted
      to CDC the following analysis as its official comments on the revised rules.

PMID- 16792490
TI  - Hospital preparedness for pandemic influenza.

PMID- 16792502
TI  - Microarray and large-scale in silico--based identification of genes functionally
      related to Haptoglobin and/or Hemopexin.
AB  - Haptoglobin and Hemopexin are plasma acute phase proteins that bind with high
      affinity hemoglobin and heme, respectively. They play a key role in the
      protection against oxidative stress and inflammation. To dissect in more detail
      the mechanism of action of Haptoglobin and Hemopexin, it is important to identify
      their downstream effectors as well as genes functionally related to them. To this
      end, we performed a cDNA microarray analysis to compare gene expression profiles
      of the liver of Haptoglobin and Hemopexin single and double null mice to that of
      wild-type controls. Then, to extract the best candidates considered to be
      functionally related to Haptoglobin and/or Hemopexin from microarray-derived gene
      lists, we used a bioinformatic approach consisting in the screening of published
      microarray data for genes showing coexpression with Haptoglobin or Hemopexin.
      This strategy allowed us to identify a group of genes coexpressed with
      Haptoglobin or Hemopexin and transcriptionally modulated by their lack. These
      genes present a high probability to be functionally related to Haptoglobin and
      Hemopexin. Based on literature data, we picked up from this group of genes the
      ras suppressor Rsu1, the member of the G-protein signal transduction family
      Gnai2, and the cytokine Mdk as the best candidates mediating the anti
      inflammatory action of Haptoglobin and Hemopexin.

PMID- 16792503
TI  - trnp: A conserved mammalian gene encoding a nuclear protein that accelerates cell
      cycle progression.
AB  - We herein describe a novel protein encoded by a single exon in a single-copy
      conserved mammalian gene. This protein, termed TMF regulated nuclear protein
      (TRNP), was identified in a yeast "two-hybrid" screen in which the "BC box"
      containing protein-TMF/ARA160 served as a bait. TRNP is a basic protein which
      accumulates in an insoluble nuclear fraction in mammalian cells. It is 227 aa
      long in humans and chimps and 223 aa long in mice. Enforced expression of TRNP in
      cells that do not express this protein significantly increased their
      proliferation rate by enhancing their cell-cycle progression from the G0/G1 to
      the S phase. Like another proliferation promoting factor, Stat3, TRNP was
      directed to proteasomal degradation by TMF/ ARA160. Thus, the trnp gene encodes a
      novel mammalian conserved nuclear protein that can accelerate cellcycle
      progression and is regulated by TMF/ARA160.

PMID- 16792504
TI  - PU.1 is degraded in differentiation of erythrocytes through a proteasome
      dependent pathway.
AB  - The transcription factor PU.1 regulates erythrocyte differentiation. We
      previously reported that F5-5 erythroblasts differentiate into erythrocytes in
      response to activin by degrading PU.1, and that inhibiting PU.1- degradation
      suppresses F5-5 cell differentiation into erythrocytes. These findings suggest
      that regulating PU.1 degradation is critical for terminal differentiation of
      erythrocytes. Here, we investigate the mechanism underlying PU.1 degradation
      during successive differentiation of erythrocytes. Using 2D-MS proteomic
      analysis, we show that proteasome subunits and proteins required for degradation
      by proteasomes immunoprecipitate with PU.1 in response to activin. Furthermore, a
      proteasome inhibitor, lactacystin, partially suppresses differentiation of F5-5
      cells into erythrocytes in response to activin, and partially inhibits PU.1
      degradation. Our results indicate that degradation of PU.1 necessary for
      erythrocyte differentiation occurs, in part, through the proteasome pathway.

PMID- 16792505
TI  - Cloning and characterization of the BRD7 gene promoter.
AB  - BRD7, a novel bromodomain gene, encodes a protein that inhibits cell growth and
      cell cycle progression by transcriptional regulation of some cell cycle-related
      genes. Its transcriptional down-expression has been shown to be critical to the
      pathogenesis of Nasopharyngeal carcinoma (NPC). Little is known about the
      transcriptional mechanisms controlling BRD7 gene expression. In this paper, we
      have characterized the 5' regulatory region of the BRD7 gene in order to
      understand the molecular mechanisms regulating its expression. Transient
      transfection results suggested that the analyzed upstream sequences of the BRD7
      gene might contain some important but not sufficient sequence information to
      confer the cell-type specificity of BRD7 gene expression. Further analysis with a
      series of deletions demonstrated that a 125-bp region was required for the basal
      promoter activity of the BRD7 gene. Results from ChIP and EMSA indicated that the
      promoter was responsive to Sp1, E2F, and E2F6. All of these suggest a possible
      mechanism that transcriptional factor Sp1, E2F, and E2F-6 are associated in the
      BRD7 promoter region and regulate BRD7 promoter activity. Taken together, these
      results will help to better understand the role of the BRD7 gene in signal
      dependent transcriptional regulation, and to develop new reagents for therapeutic
      upregulation of the BRD7 gene in NPC.

PMID- 16792506
TI  - Increased recombination between active tRNA genes.
AB  - Transfer RNA genes are distributed throughout eukaryotic genomes, and are
      frequently found as multicopy families. In Saccharomyces cerevisiae, tRNA gene
      transcription by RNA polymerase III suppresses nearby transcription by RNA
      polymerase II, partially because the tRNA genes are clustered near the nucleolus.
      We have tested whether active transcription of tRNA genes might also suppress
      recombination, since recombination between identical copies of the repetitive
      tRNA genes could delete intervening genes and be detrimental to survival. The
      opposite proved to be the case. Recombination between active tRNA genes was
      elevated, but only when both genes are transcribed. We also tested the effects of
      tRNA genes on recombination between the direct terminal repeats of a neighboring
      retrotransposon, since most Ty retrotransposons reside next to tRNA genes, and
      the selective advantage of this arrangement is not known.

PMID- 16792507
TI  - Origin of the genetic code: first aminoacyl-tRNA synthetases could replace
      isofunctional ribozymes when only the second base of codons was established.
AB  - Analysis of the updated compilation of more than 8,000 tRNA gene sequences
      confirmed our previously reported finding that in pairs of consensus tRNAs with
      complementary anticodons, their second bases in the acceptor stems are also
      complementary. This dual complementarity points to the following: (1) the
      operational code embodied in the acceptor stem, and the classic genetic code
      embodied in the anticodon could have had the same common ancestor; (2) new tRNAs
      most likely entered primitive translation in pairs with complementary anticodons;
      and (3) this process of code expansion was directed by the primordial double
      strand coding. However, we did not find the dual complementarity when testing all
      tRNA pairs in which anticodons were complementary only at the central position,
      but not complementary at least at one of the flanking two positions. This
      observation, together with certain additional evidence, suggests that both codes
      were still being shaped (with only the second base established at the time) when
      the first protein aminoacyl-tRNA synthetases could have already started replacing
      their ribozymic precursors.

PMID- 16792508
TI  - Genetic ablation of Ptprj, a mouse cancer susceptibility gene, results in normal
      growth and development and does not predispose to spontaneous tumorigenesis.
AB  - Ptprj is a ubiquitously expressed murine gene encoding a receptor-type protein
      tyrosine phosphatase, which has recently been proposed as a candidate gene on the
      locus Scc1 for colon cancer susceptibility. It has been demonstrated that PTPRJ,
      the human homologue of Ptprj, is involved in the control of cell growth and
      adhesion, being furthermore altered in several types of cancer including mammary,
      thyroid, lung, colon, and pancreatic cancers. To investigate the biological
      functions of Ptprj, we have generated mice deficient in this receptor protein
      tyrosine phosphatase. Ptprj-deficient mice are viable, fertile, and show no gross
      anatomical alterations. Furthermore, neither changes in life span nor spontaneous
      tumor appearance were observed in Ptprj-null mice. Our results indicate that
      Ptprj is dispensable for normal growth and development in mice.

PMID- 16792510
TI  - Molecular genetic testing for familial hypercholesterolemia in the Netherlands: a
      stepwise screening strategy enhances the mutation detection rate.
AB  - Familial hypercholesterolemia (FH) has been identified as a major risk factor for
      coronary vascular disease and is associated with mutations in the low-density
      liporotein receptor (LDLR) and apolipoprotein B (APOB) gene. The molecular basis
      of FH in the Dutch population is well understood. Approximately 160 different
      LDLR and APOB gene defects have been identified with a panel of 9 LDLR gene and 1
      APOB gene frequently occurring mutations accounting for approximately 30% of all
      clinically diagnosed FH cases. As molecular diagnosis of FH is becoming
      increasingly widely applied, a variety of mutation detection rates is reported,
      ranging from as low as 30% and up to 80%. This variability appears to depend on
      the clinical criteria applied to identify patients with FH and on the strategies
      and methodologies used for mutation screening. In this study we describe the
      application of a stepwise screening approach, combining different methodologies,
      to detect mutations of the LDLR gene and APOB gene in 1465 patients with FH. A
      mutation was found in approximately 44% of the patients, which demonstrates that
      this is an effective strategy for the molecular diagnosis of FH.

PMID- 16792511
TI  - Simple procedure for automatic detection of unstable alleles in the myotonic
      dystrophy and Huntington's disease loci.
AB  - Human neurodegenerative and neuromuscular disorders are associated with a class
      of gene mutations represented by expansion of trinucleotide repeats. DNA testing
      is important for the diagnosis of these diseases because clinical discrimination
      is complicated by their late onset and frequently overlapping symptomatology.
      However, detection of pathologic alleles expanded up to several thousand
      trinucleotides poses a challenge for the introduction of rapid, fully automatic,
      and simple DNA diagnostic procedures. Here we propose a simple two-step
      polymerase chain reaction (PCR) protocol for rapid molecular diagnostics of
      myotonic dystrophy, Huntington's disease, and possibly also other triplet
      expansion diseases. Standard PCR amplification with target repeat flanking
      primers is used for the detection of alleles of up to 100 repeats; next, triplet
      primed PCR is applied for detection of larger expansions. Automated capillary
      electrophoresis of amplicons allows rapid discrimination between normal,
      premutated and expanded (CTG/CAG)(n) alleles. Using the suggested protocol, the
      expanded allele was successfully detected in all test DNA samples with known
      genotypes. Our experience demonstrates that the suggested two-step PCR protocol
      provides high sensitivity, specificity, and reproducibility; is significantly
      less time-consuming; is easier to perform; and provides a better basis for
      automation than previous methods requiring Southern analysis. Therefore, it can
      be used for confirmation of uncertain clinical diagnoses, for prenatal testing in
      at-risk families, and, generally in research on these diseases.

PMID- 16792512
TI  - A high-resolution polymerase chain reaction-sequence-specific primer HLA-B*27
      typing set and its application in routine HLA-B27 testing.
AB  - We designed a set of 35 polymerase chain reaction sequence-specific primers (PCR
      SSP) in 29 SSP mixtures to assign 29 HLA-B*27 4-digit level alleles (B*2701
      B*2721 and B*2723-B*2730). This was used in conjunction with our 41 PCR-SSP
      primer mixture low-resolution HLA-B typing set to fully differentiate B*27 from
      all other HLA-B alleles. Successful typing set validation used 521 B*27 samples
      covering 13 (B*2701-B*2710 and B*2712, B*2717, B*2723) alleles. The distribution
      of B*27 alleles was determined in a random population of 4020 local blood donors
      and the use of PCR-SSP B*27 typing in our routine flow cytometry-based HLA
      B27/B2708 typing strategy is described.

PMID- 16792513
TI  - No Evidence of BRCA1/2 genomic rearrangements in high-risk French-Canadian
      breast/ovarian cancer families.
AB  - The discovery of deleterious mutations in the breast and ovarian cancer
      susceptibility genes, BRCA1 and BRCA2, has facilitated the identification of
      individuals at particularly high risk of these diseases. There is a wide
      variation between populations in the prevalence and related risks of various
      types of BRCA1/2 mutations, so estimates cannot be extrapolated to Canadians,
      especially not founder populations such as French- Canadians. Polymerase chain
      reaction (PCR)-based methods were used to detect the majority of these mutations.
      These approaches usually failed to detect large DNA rearrangements, which have
      been claimed to be involved in other populations in 5% to up to 36% of BRCA1
      positive families. There is very little information about the contribution of
      this type of mutation in BRCA2-positive families. To investigate if our available
      mutation spectrum of BRCA1 and BRCA2 in high-risk French-Canadian breast/ovarian
      cancer families has been biased by PCR-based direct sequencing methods, we first
      used Southern blot analysis to test DNA samples from 61 affected/obligate carrier
      individuals from 58 families in which no BRCA1/2 deleterious mutation was found.
      Finally, 154 individuals from 135 BRCA1/2 nonconclusive families, including all
      those tested previously by Southern blot analysis, were tested with the new
      multiplex ligation probe amplification (MLPA) technique. These approaches failed
      to detect any rearrangement. Moreover, if the frequency of MLPA-detectable
      rearrangements in our cohort of 135 BRCA1/2 nonconclusive families was 2.2% or
      higher, we would have had a 95% or greater chance of observing at least one such
      rearrangement. As no rearrangements were identified, such large rearrangements
      must be quite rare in our population.

PMID- 16792514
TI  - A missense mutation in exon 13 in BRCA2, c.7235G>A, results in skipping of exon
      13.
AB  - We report here the functional characterisation of a missense mutation c.7235G>A
      in BRCA2. By reverse transcriptase polymerase chain reaction the mutation is
      demonstrated to cause skipping of exon 13. We conclude that the mutation is most
      likely deleterious.

PMID- 16792515
TI  - Combined test for UGT1A1 -3279T-->G and A(TA)nTAA polymorphisms best predicts
      Gilbert's syndrome in Italian pediatric patients.
AB  - Gilbert's syndrome is a common hereditary chronic or recurrent, mild unconjugated
      hyperbilirubinemia. Polymorphisms in the bilirubin uridine diphosphate
      glucuronosyl transferase gene (UGT1A1) causing a decreased enzyme activity are
      associated with susceptibility to the syndrome. Homozygosity for TA(7) allele of
      the A(TA)(n)TAA promoter polymorphism is found in the majority of Caucasian
      patients. We sought to investigate the role of three UGT1A1 polymorphisms
      (A[TA](n)TAA, -3279T-->G, and G71R) in the susceptibility to Gilbert's syndrome
      in 53 Italian pediatric subjects compared to 83 unaffected controls. Carriage of
      two TA(n) risk alleles (TA(7) and TA(8)) and -3279G homozygosity were similarly
      associated with hyperbilirubinemia (odds ratio [OR] = 11.59, 95% confidence
      interval [CI] = 4.80-27.98; p < 0.001, and OR = 11.51, 95% CI = 5.06-26.19; p <
      0.001, respectively). Homozygosity for both TA7 and -3279G was associated with
      the highest relative risk estimate (OR = 19.23, 95% CI = 7.34-50.4; p < 0.001),
      but a significant association was found also for TA7 heterozygosity combined with
      -3279G/G genotype (OR = 7.98, 95% CI = 2.54-25.06; p < 0.001). The G71R variant
      was found only in two controls. Our results demonstrate that genotyping of both
      UGT1A1 A(TA)(n)TAA and -3279T-->G polymorphisms best defines genetic
      susceptibility to Gilbert's syndrome in Caucasian pediatric patients, and the TA7
      heterozygous genotype combined with homozygosity for the -3279G allele can also
      be associated with pediatric mild hyperbilirubinemia.

PMID- 16792516
TI  - Optimized pH method for DNA elution from buccal cells collected in Whatman FTA
      cards.
AB  - DNA is the most accessible biologic material for obtaining information from the
      human genome because of its molecular stability and its presence in every
      nucleated cell. Currently, single nucleotide polymorphism genotyping and DNA
      methylation are the main DNA-based approaches to deriving genomic and epigenomic
      disease biomarkers. Upon the discontinuation of the Schleicher & Schuell IsoCode
      product (Dassel, Germany), which was a treated paper system to elute DNA from
      several biologic sources for polymerase chain reaction (PCR) analysis, a high
      yielding DNA elution method was imperative. We describe here an improved
      procedure of the not fully validated Whatman pH-based elution protocol. Our DNA
      elution procedure from buccal cells collected in Whatman FTA cards (Whatman Inc.,
      Florham Park, NJ) yielded approximately 4 microg of DNA from a 6-mm FTA card
      punch and was successfully applied for HLA-DQB1 genotyping. The genotypes showed
      complete concordance with data obtained from blood of the same subjects. The
      achieved high DNA yield from buccal cells suggests a potential cost-effective
      tool for genomic and epigenomic disease biomarkers development.

PMID- 16792517
TI  - Psychosocial correlates of pregnant women's attitudes toward prenatal maternal
      serum screening and invasive diagnostic testing: beyond traditional risk status.
AB  - This study examined whether psychosocial variables predict pregnant women's
      attitudes toward maternal serum screening and invasive diagnostic testing, beyond
      the influence of traditional obstetric risk status (based on advanced maternal
      age, history of genetic disorders, etc.). In a sample of 612 pregnant women
      (66.5% high risk, 33.5% low risk) we assessed responses to hypothetical scenarios
      of invasive testing following normal or abnormal maternal serum screening. We
      also assessed psychosocial variables stemming from the theory of planned behavior
      (e.g., knowledge, concern for fetus, attitudes toward termination, health locus
      of control). Overall, two thirds of the women would want serum screening. Follow
      up invasive diagnostic testing would be sought by 37.2% of the women after a
      negative screening, and by 75.0% after a positive screening. As expected,
      traditional risk status predicted desire for screening and also invasive testing
      following either a negative or positive screen. Yet, controlling for risk status,
      many psychosocial variables predicted a women's interest in screening and in
      invasive testing: more knowledge about prenatal testing, concern about fetal
      health, willingness to terminate a pregnancy, and an internal or medical
      profession health locus of control. We conclude that psychosocial variables
      influence women's desire for screening or invasive testing beyond traditional
      risk status.

PMID- 16792520
TI  - Marshall Parks, M.D. Extraordinary mentor, exemplary physician. Comments on his
      monofixation syndrome and VVDA.

PMID- 16792518
TI  - Public attitudes toward genetic testing: perceived benefits and objections.
AB  - The aim of this study was to assess public attitudes toward the availability and
      use of genetic tests to explore support for genomics developments and to help
      improve public discussion. Questionnaires to assess the assumed advantages and
      disadvantages of genetic testing were sent to a representative sample of the
      Dutch population (n = 1,308; age > or =25 years). The response was 63%
      (817/1,308). Two groups with extreme scores on a four-item scale were
      distinguished, representing opponents (n = 248) and supporters (n = 264) of the
      availability and use of genetic tests. Multiple logistic regression analyses
      showed that those who were familiar with a genetic disease (odds ratio [OR] 0.54;
      95% confidence interval [CI] 0.32-0.89; p = 0.015), those who scored higher on a
      four-item scale on belief in personal benefits of testing (OR 0.29; 95% CI 0.21
      0.40; p < 0.0001), and those who believe that knowledge of the genetic background
      of disease will help people to live more healthy lives (OR 0.48; 95% CI 0.37
      0.62; p < 0.0001), were less likely to be opponents. Those who agreed that
      genetic testing is tampering with nature (OR 1.63; 95% CI 1.32-2.00; p < 0.0001)
      were more likely to be opponents. Other variables such as belief in genetic
      determinism, genetic knowledge, level of education, age, and gender were not
      significantly associated. These results suggest that in addition to moral
      acceptability, perceived usefulness is a precondition for supporting genetic
      testing. It is not expected that more information will necessarily result in more
      positive attitudes.

PMID- 16792521
TI  - Compared value of amblyopia detection.

PMID- 16792522
TI  - Incompetence: now the rule instead of the exception. Protect yourself at all
      times.

PMID- 16792523
TI  - The 10th Bielschowsky Lecture. Changes in strabismus over time: the roles of
      vergence tonus and muscle length adaptation.
AB  - Patients with long-standing unilateral strabismus, such as "sensory" exotropia in
      the absence of fusion, or esotropia with unilateral amblyopia, typically show
      bilateral deviations under anesthesia, often symmetric. Forced ductions usually
      show symmetric muscle tightness. Changes in extraocular muscle lengths thus
      appear to occur primarily bilaterally, whether fusion is present or not. With
      skeletal muscles responding to changes in stimulation by the gain or loss of
      sarcomeres, it is likely that abnormal or unguided vergence tonus, which changes
      the lengths of the extraocular muscles bilaterally, is largely responsible for
      changes in the angle of strabismus over time. This mechanism helps explain the
      development of [1] increasing "basic" deviations in accommodative esotropia; [2]
      torsional deviations with apparent oblique muscle "overaction/underaction" and A
      and V patterns; [3] recurrent esotropia with early presbyopia; [4] occasional
      divergence insufficiency in presbyopes; and [5] basic cyclovertical deviations
      that mimic superior oblique muscle paresis.

PMID- 16792524
TI  - The yield and challenges of charitable state-wide photoscreening.
AB  - INTRODUCTION: State-wide cooperative programs for pediatric vision screening
      utilizing the MTI photoscreener and centralized interpretation were established
      in Alaska (The Alaska Blind Child Discovery, ABCD) and in Tennessee (Tennessee
      Lions Outreach). METHODS: Details of setup, implementation and interpretation of
      the state-wide MTI photoscreening programs are compared through 2002. The
      absolute numbers of children screened and the breakdown in interpretation
      categories are presented. RESULTS: ABCD screened 14,000 children while Tennessee
      Lions screened 100,800. Similarities between ABCD and Tennessee programs were
      funded by Lions Clubs and other charitable and public health organizations,
      community screening and each had coordinated centralized image interpretation and
      notification. The programs differed by clinic focus (Tennessee Lions organized
      pre-schools while ABCD used village and community health fairs and schools),
      parent notification (Tennessee Lions communicated through pre- schools and ABCD
      mailed directly to parents), and image interpretation (Tennessee used VOIC age
      based and pupil-size crescents while ABCD used "delta-center crescent").
      Predictive value positive was 73% for Tennessee and 89% for ABCD. Tennessee
      achieved better followup on referrals after a specific coordinator was employed.
      Image interpretation breakdown for ABCD: Tennessee Lions Outreach were
      anisometropia (29%:34%), high hyperopia (33%:16%), astigmatism (18%:30%),
      strabismus (7%:15%), myopia (5%:2%), cataract (0.7%:0.2%). Two state-wide
      programs detected 3216 amblyopic children at a charity borne-cost of 1.5 million
      dollars. If the parents persisted with appropriate amblyopia therapy, the
      expected societal value was estimated at 17 million dollars. Lacking societal
      mandate and funding, these concerted charitable efforts only achieved a community
      penetration rate of 10% to 14%. CONCLUSION: National adoption of preschool vision
      screening by a method with similar or even better validity and cost effectiveness
      as MTI photoscreening, ideally in the pediatric medical home, is warranted.

PMID- 16792525
TI  - Modulation of inhibition of ferrochelatase by N-methylprotoporphyrin.
AB  - Protoporhyrin IX ferrochelatase catalyses the terminal step of the haem
      biosynthetic pathway by inserting ferrous iron into protoporphyrin IX. NMPP (N
      methylprotoporphyrin), a transition-state analogue and potent inhibitor of
      ferrochelatase, is commonly used to induce haem deficiency in mammalian cell
      cultures. To create ferrochelatase variants with different extents of tolerance
      towards NMPP and to understand further the mechanism of ferrochelatase inhibition
      by NMPP, we isolated variants with increased NMPP resistance, bearing mutations
      in an active-site loop (murine ferrochelatase residues 248-257), which was
      previously shown to mediate a protein conformational change triggered by
      porphyrin binding. The kinetic mechanisms of inhibition of two variants, in which
      Pro255 was replaced with either arginine (P255R) or glycine (P255G), were
      investigated and compared with that of wild-type ferrochelatase. While the
      binding affinity of the P255X variants for NMPP decreased by one order of
      magnitude in relation to that of wild-type enzyme, the inhibition constant
      increased by approximately two orders of magnitude (K(i)(app) values of 1 microM
      and 2.3 microM for P255R and P255G respectively, as against 3 nM for wild-type
      ferrochelatase). Nonetheless, the drastically reduced inhibition of the variants
      by NMPP was not paralleled with a decrease in specificity constant (kcat/K(m,
      protoporhyrin IX)) and/or catalytic activity (kcat). Further, although NMPP
      binding to either wild-type ferrochelatase or P255R occurred via a similar two
      step kinetic mechanism, the forward and reverse rate constants associated with
      the second and rate-limiting step were comparable for the two enzymes.
      Collectively, these results suggest that Pro255 has a crucial role in maintaining
      an appropriate protein conformation and modulating the selectivity and/or
      regiospecificity of ferrochelatase.

PMID- 16792528
TI  - The KRAB-associated co-repressor KAP-1 is a coiled-coil binding partner,
      substrate and activator of the c-Fes protein tyrosine kinase.
AB  - The c-Fes protein tyrosine kinase is implicated in the differentiation of a
      number of cell types including neuronal, endothelial and myeloid cells.
      Structurally, Fes consists of a unique N-terminal region, followed by SH2 (Src
      homology domain 2) and kinase domains. Two coiled-coil (CC) domains (CC1 and CC2)
      located within the unique N-terminal region are critical regulators of Fes
      activity in vivo and may function to recruit Fes activators and/or substrates. A
      yeast two-hybrid screen, utilizing a K-562 cell cDNA library and the Fes CC2
      domain as bait, identified an interacting clone encoding the CC domain and B-box
      motifs (residues 114-357) of the transcriptional co-repressor KRAB-associated
      protein (KAP)-1. KAP-1(114-357) interacted with full-length Fes in yeast, and the
      KAP-1 CC domain was sufficient to bind the Fes N-terminal region in Sf-9 cells.
      Co-expression of Fes with full-length KAP-1 in human 293T cells stimulated Fes
      autophosphorylation and led to KAP-1 tyrosine phosphorylation. Association of
      endogenous Fes and KAP-1 was also observed in HL-60 myeloid leukaemia cells.
      Together, these data identify a novel Fes-KAP-1 interaction, and suggest a dual
      role for KAP-1 as both a Fes activator and downstream effector.

PMID- 16792527
TI  - Control and regulation of the cellular responses to cold shock: the responses in
      yeast and mammalian systems.
AB  - Although the cold-shock response has now been studied in a number of different
      organisms for several decades, it is only in the last few years that we have
      begun to understand the molecular mechanisms that govern adaptation to cold
      stress. Notably, all organisms from prokaryotes to plants and higher eukaryotes
      respond to cold shock in a comparatively similar manner. The general response of
      cells to cold stress is the elite and rapid overexpression of a small group of
      proteins, the so-called CSPs (cold-shock proteins). The most well characterized
      CSP is CspA, the major CSP expressed in Escherichia coli upon temperature
      downshift. More recently, a number of reports have shown that exposing yeast or
      mammalian cells to sub-physiological temperatures (<30 or <37 degrees C
      respectively) invokes a co-ordinated cellular response involving modulation of
      transcription, translation, metabolism, the cell cycle and the cell cytoskeleton.
      In the present review, we summarize the regulation and role of cold-shock genes
      and proteins in the adaptive response upon decreased temperature with particular
      reference to yeast and in vitro cultured mammalian cells. Finally, we present an
      integrated model for the co-ordinated responses required to maintain the
      viability and integrity of mammalian cells upon mild hypothermic cold shock.

PMID- 16792526
TI  - In control of biology: of mice, men and Foxes.
AB  - Forkhead proteins comprise a highly conserved family of transcription factors,
      named after the original forkhead gene in Drosophila. To date, over 100 forkhead
      genes have been identified in a large variety of species, all sharing the
      evolutionary conserved 'forkhead' DNA-binding domain, and the cloning and
      characterization of forkhead genes have continued in recent years. Forkhead
      transcription factors regulate the expression of countless genes downstream of
      important signalling pathways in most, if not all, tissues and cell types. Recent
      work has provided novel insights into the mechanisms that contribute to their
      functional diversity, including functional protein domains and interactions of
      forkheads with other transcription factors. Studies using loss- and gain-of
      function models have elucidated the role of forkhead factors in developmental
      biology and cellular functions such as metabolism, cell division and cell
      survival. The importance of forkhead transcription factors is underlined by the
      developmental defects observed in mutant model organisms, and multiple human
      disorders and cancers which can be attributed to mutations within members of the
      forkhead gene family. This review provides a comprehensive overview of current
      knowledge on forkhead transcription factors, from structural organization and
      regulatory mechanisms to cellular and developmental functions in mice and humans.
      Finally, we will discuss how novel insights gained from involvement of 'Foxes' in
      the mechanisms underlying human pathology may create new opportunities for
      treatment strategies.

PMID- 16792531
TI  - Abstracts and poster abstracts from the 4th European Congress of Reproductive
      Immunology. July 5-9, 2006. Graz, Austria.

PMID- 16792529
TI  - A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda.
AB  - WD (tryptophan-aspartic acid dipeptide)-repeat proteins play a central role in
      signal transduction cascades by co-ordinating the interaction of key signalling
      molecules. We identified a novel propeller-FYVE [domain identified in Fab1p,
      YOTB, Vac1p and EEA1 (early endosome antigen 1)] protein, ProF, which is
      expressed in various cell lines and tissues and consists of seven WD-repeats and
      a FYVE domain. WD-repeat proteins offer a platform for protein-protein
      interactions by folding into a seven-bladed propeller-like structure, while the
      FYVE domain binds to phosphatidylinositol 3-phosphate present mainly on
      intracellular membranes. The ProF protein partially co-localizes with EEA1 on
      vesicular structures and binds to the protein kinases Akt and PKCzeta/lambda
      (protein kinase Czeta/lambda) via its WD-repeat propeller. ProF interacts more
      strongly with the kinases after hormonal stimulation. Endogenously expressed ProF
      and the two kinases interact in brain and in the preadipocyte cell line 3T3-L1,
      suggesting a role in secretory vesicular processes. In summary, we describe a new
      binding partner for kinases, located on vesicular structures in specialized
      cells, which may play a role for the spatial organization of signalling cascades.

PMID- 16792530
TI  - In vivo binding of NF-kappaB to the IkappaBbeta promoter is insufficient for
      transcriptional activation.
AB  - Despite certain structural and biochemical similarities, differences exist in the
      function of the NF-kappaB (nuclear factor kappaB) inhibitory proteins
      IkappaBalpha (inhibitory kappaBalpha) and IkappaBbeta. The functional disparity
      arises in part from variance at the level of gene regulation, and in particular
      from the substantial induction of IkappaBalpha, but not IkappaBbeta, gene
      expression post-NF-kappaB activation. In the present study, we probe the
      differential effects of IL (interleukin)-1beta on induction of IkappaBalpha and
      perform the first characterization of the human IkappaBbeta promoter. A consensus
      NF-kappaB-binding site, capable of binding NF-kappaB both in vitro and in vivo,
      is found in the IkappaBbeta gene 5' flanking region. However, the IkappaBbeta
      promoter was not substantially activated by pro-inflammatory cytokines, such as
      IL-1beta and tumour necrosis factor alpha, that are known to cause strong
      activation of NF-kappaB. Furthermore, in contrast with IkappaBalpha, NF-kappaB
      activation did not increase expression of endogenous IkappaBbeta as assessed by
      analysis of mRNA and protein levels. Unlike kappaB-responsive promoters,
      IkappaBbeta promoter-bound p65 inefficiently recruits RNA polymerase II, which
      stalls at the promoter. We present evidence that this stalling is likely due to
      the absence of transcription factor IIH engagement, a prerequisite for RNA
      polymerase II phosphorylation and transcriptional initiation. Differences in the
      conformation of promoter-bound NF-kappaB may underlie the variation in the
      ability to engage the basal transcriptional apparatus at the IkappaBbeta and
      kappaB-responsive promoters. This accounts for the differential expression of
      IkappaB family members in response to NF-kappaB activation and furthers our
      understanding of the mechanisms involved in transcription factor activity and
      IkappaBbeta gene regulation.

PMID- 16792532
TI  - Granulocyte-macrophage colony-stimulating-factor increases interferon-tau protein
      secretion in bovine trophectoderm cells.
AB  - PROBLEM: Uterine-derived factors are required for optimal conceptus development
      and secretion of the maternal recognition of pregnancy factor, interferon-tau
      (IFN-tau). Identifying these factors may lead to the development of schemes for
      increasing pregnancy success in cattle. METHOD OF STUDY: The objectives were to
      examine the effects of granulocyte-macrophage colony-stimulating-factor (GM-CSF)
      on trophectoderm proliferation rates and IFN-tau production, and verify the
      appropriateness of using an in vitro model of bovine trophectoderm (CT-1 cell).
      RESULTS: Rate of [(3)H]-thymidine incorporation into DNA was increased by
      supplementation of CT-1 medium with 10 or 100 ng/mL porcine (po) GM-CSF. GM-CSF
      supplementation to CT-1 medium also increased IFN-tau secretion. When results
      were normalized to account for number of CT-1 cells, 10 and 100 ng/mL poGM-CSF
      increased antiviral activity and IFN-tau concentrations (using an IFN-tau
      specific enzyme-linked immunosorbent assay) in CT-1 conditioned medium compared
      with controls. CONCLUSIONS: These findings indicate that GM-CSF increases
      proliferation and IFN-tau production in bovine trophectoderm.

PMID- 16792533
TI  - Soluble HLA-G molecules induce apoptosis in natural killer cells.
AB  - Membrane-bound human leukocyte antigen-G (HLA-G) molecules are primarily
      expressed by cytotrophoblasts of the fetus. They are thought to protect the fetus
      from immunologic attack by the maternal immune system and have recently been
      associated with transplantation graft acceptance. In addition, soluble HLA-G
      molecules (sHLA-G) have been shown to play a role in the success of pregnancies,
      but are upregulated in certain cancers. However, the exact mechanism for this
      regulation has remained elusive. The aim of this study was to examine the
      mechanism by which sHLA-G interact with natural killer (NK) cells in vitro. sHLA
      G effectively blocked NK lysis of target cells via fracticide killing of NK cells
      by apoptosis. These studies support the protective role of sHLA-G in immunologic
      reactions by interacting with NK cells, thus providing a regulatory function.

PMID- 16792534
TI  - Elevated peripheral natural killer cell and infertility.

PMID- 16792535
TI  - Mutations affecting the replication capacity of the hepatitis B virus.
AB  - The genetic variability of the hepatitis B virus (HBV) encounters two compounding
      forces: a high viral copy number produced during active replication and the lack
      of proofreading activity in the HBV polymerase, resulting in a high mutational
      rate. A large pool of quasispecies is generated in which the fittest virus, i.e.
      the virus that replicates best, becomes the dominant species. Immune and
      antiviral selection pressures result in vaccine/immunoglobulin escape mutants and
      antiviral resistant variants. Viruses encoding changes associated with antiviral
      resistance often have reduced replication in vitro, but the accumulation of
      additional mutations helps restore viral fitness. These compensatory mutations
      may occur not only in the polymerase gene but also in other genes such as the
      overlapping envelope gene, the precore gene, or in regulatory regions such as the
      basal core promoter. In this report we aim to review the new findings that have
      appeared in recent months.

PMID- 16792536
TI  - Re-treatment of chronic hepatitis C patients after relapse: efficacy of
      peginterferon-alpha-2a (40 kDa) and ribavirin.
AB  - We conducted a randomized multinational study to determine whether 48 weeks of re
      treatment with peginterferon-alpha-2a (40 kDa) plus ribavirin would induce a
      sustained virological response (SVR) in relapsed chronic hepatitis C patients.
      Patients who had previously relapsed during 24 weeks of untreated follow-up,
      after having achieved an end-of-treatment virological response with 24 weeks of
      peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III
      trial, were studied. Although the recommended dosage was the same as that used at
      the end of the initial trial, adjustments were permitted. Data on serious adverse
      events, or adverse events that resulted in dose reductions or discontinuations,
      were collected. Following re-treatment, the overall SVR rate in the 64 patients
      was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype
      1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological
      responses were seen in 39 patients (61%) and were predictive of an SVR. Re
      treatment was well tolerated. The most frequent adverse events recorded were
      fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa)
      and/or ribavirin were modified because of adverse events in 3% and 13% of
      patients, and because of laboratory abnormalities in 23% and 5% of patients,
      respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus
      ribavirin induces an SVR in 55% of patients who relapsed during follow-up after
      24 weeks of combination therapy. Physicians should not hesitate to offer re
      treatment to patients who relapse after an initial, 24-week course of combination
      therapy, or who have prematurely stopped treatment because, for example, of
      laboratory abnormalities.

PMID- 16792537
TI  - Effects of bezafibrate in patients with chronic hepatitis C virus infection:
      combination with interferon and ribavirin.
AB  - An association of hepatitis C virus (HCV) with low-density lipoproteins (LDL) in
      serum of patients with chronic hepatitis C (CHC) has been suggested. We conducted
      a prospective study in CHC patients complicated with hyperlipidaemia, to examine
      whether bezafibrate, which is commonly used for treatment of hyperlipidaemia,
      reduces serum HCV-RNA titre and improves liver dysfunction. Fifteen patients
      received daily oral bezafibrate treatment (400 mg/day) for 8 weeks, and its
      effects on serum lipids, transaminases, HCV-RNA titres, and HCV-RNA titres bound
      to LDL were evaluated. Fifteen untreated patients with CHC and hyperlipidaemia
      were used as controls. The mean serum alanine aminotransferase levels and HCV-RNA
      titres significantly decreased at the end of bezafibrate therapy in the treated
      group (105 +/- 34 to 80 +/- 32 IU/L, P = 0.02 and 2.23 +/- 2.71 to 1.78 +/- 2.38
      x 10(7) copies/mL, P < 0.01 respectively), but no changes were observed in the
      control group. Serum HCV-RNA titres bound to LDL, as quantified by
      immunoprecipitation using anti-LDL antibody, also decreased in all 15 treated
      patients [5.55 +/- 6.59 to 1.07 +/- 1.58 x 10(6) copies/ml, P < 0.01 (mean
      reduction rate was -78.5 +/- 17.0%)]. Sucrose density-gradient
      ultracentrifugation study revealed that HCV-RNA-decreased density fractions after
      the bezafibrate were identical to LDL-density fractions (1.015-1.062 g/mL). Eight
      CHC patients were treated with bezafibrate, interferon, and ribavirin triple
      therapy for 32 weeks, and four patients achieved sustained virological response
      to therapy. This pilot study provides further evidence of an association between
      HCV and LDL in serum and suggests the potential usefulness of bezafibrate as an
      anti-HCV reagent for the treatment of CHC patients.

PMID- 16792538
TI  - Insulin resistance is not associated with liver fibrosis progression in
      HIV/hepatitis C virus-coinfected patients.
AB  - Insulin resistance (IR) is a common condition in chronic hepatitis C. Recent
      studies have reported that IR is associated with liver fibrosis progression in
      these patients. However, there is no information available on this issue in human
      immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. For
      these reasons, we investigate the relationship between IR and liver fibrosis in
      patients with HIV and HCV infections. This was a cross-sectional study where
      patients from an Infectious Diseases Unit with HIV/HCV coinfection who underwent
      a liver biopsy, with available frozen sera samples at the time of biopsy and a
      known or estimated date of infection were included. IR was determined by the
      homeostasis model assessment (HOMA-IR) method. The relationship between
      histological findings and several variables, including HOMA-IR values, was
      examined. Seventy-nine patients fulfilled the inclusion criteria. Age at HCV
      infection >21 years was the only variable independently associated with advanced
      liver fibrosis (stages F3 and F4) [adjusted odds ratio (AOR) 4.15; 95% confidence
      interval (CI) 1.5-11.3]. The variables associated with a fibrosis progression
      rate above the median were age at HCV infection >21 years (AOR 6.41; 95% CI 2.16
      27.96) and previous exposure to nevirapine (AOR 8.9; 95% CI 2.01-39.36). There
      was no association between HOMA-IR values and the presence of advanced fibrosis
      or a faster fibrosis progression. Thus IR is not associated with liver damage or
      fibrosis progression in HIV/HCV-coinfected individuals.

PMID- 16792539
TI  - Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined
      with ribavirin in interferon-naive patients with chronic hepatitis C and up to
      moderate fibrosis.
AB  - Health regulatory approval of the 1.5 microg/kg body weight dose of pegylated
      interferon (PEG-I) alpha-2b in combination with ribavirin for the treatment of
      chronic hepatitis C was based on a study using PEG-I alpha-2b at doses of only
      0.5 and 1.5 microg/kg body weight (BW), in spite of the previously shown flat
      dose-response curve at doses of > or =1.0 microg/kg. Our aim was to compare PEG-I
      alpha-2b 1.0 microg/kg with 1.5 microg/kg, both in combination with ribavirin.
      Open-label, randomized study in 227 patients with biopsy-proven chronic hepatitis
      C (Metavir < or =F2), receiving oral ribavirin (400 mg, twice daily) in
      combination with subcutaneous PEG-I alpha-2b (1.0 or 1.5 microg/kg, once weekly)
      for 24 weeks (genotype 2 or 3), or 48 weeks (other genotypes), followed by a 24
      week drug-free period. Virologic response rates did not differ between the two
      doses of PEG-I alpha-2b: in patients infected with hepatitis C virus (HCV)
      genotype 1 or 4 treated with PEG-I 1.0 microg/kg BW, 38% (22/58) had a sustained
      virologic response compared with 39% (27/70) in the PEG-I 1.5 microg/kg BW dose
      group (P = ns). The corresponding values in patients infected with HCV genotype 2
      or 3 were 71% (39/55) and 81% (29/36) respectively (P = ns). Adverse events led
      to transient or permanent dose reductions in fewer patients in the 1.0 microg/kg
      BW dose group (48/113 patients; 42%) than in the 1.5 microg/kg BW dose group
      (63/106 patients; 59%, P = 0.015). Furthermore, 89% of patients treated for 24
      weeks but only 58% of patients treated for 48 weeks (P < 0.001) tolerated the
      treatment without relevant dose reduction or premature termination. In
      combination with ribavirin, PEG-I alpha-2b 1.0 microg/kg was as effective as 1.5
      microg/kg but was better tolerated in patients with chronic hepatitis C and up to
      moderate fibrosis.

PMID- 16792540
TI  - Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus
      ribavirin in HCV genotypes 1/4 according to HIV serostatus.
AB  - To evaluate, among 70 hepatitis C virus (HCV)-monoinfected and 36 human
      immunodeficiency virus (HIV)-coinfected naive patients with genotypes 1/4
      receiving weight-adjusted pegylated interferon-alpha-2b/ribavirin, viral kinetics
      and the feasibility to predict treatment failure measuring early HCV-RNA
      decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver
      operating characteristic (ROC) curves were calculated to determine the most
      sensitive cut-off values of viral decrease at week 4 predicting treatment
      failure. Baseline predictors of failure were evaluated by univariate and
      multivariate analyses. Despite similar baseline HCV-RNA (5.75 vs 5.72
      log(10)IU/ml, P = 0.6), HCV monoinfection led to significantly lower HCV-RNA
      values at weeks 4 (3.7 vs 4.3 log(10)IU/ml, P = 0.01), 12 (2.3 vs 3.5
      log(10)IU/ml, P = 0.01) and 24 (1.4 vs 3.3 log(10)IU/ml, P = 0.001) and a higher
      rates of viral clearance at weeks 24 (60%vs 36%, P = 0.02), 48 (46%vs 25%, P =
      0.03) and 72 (37%vs 17%). The lack of achieving an HCV-RNA decrease of at least 1
      log(10) at week 4 was highly predictive of treatment failure for HCV-monoinfected
      patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative
      predictive value (NPV) 100%, ROC curve area, 0.86 [95% confidence interval (CI)
      0.77-0.95], but not for HCV/HIV-coinfected patients (cut-off, 0 log(10), Se 100%,
      Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0.71 (95% CI 0.49-0.93). HIV
      coinfection was independently associated with failure (odds ratio 2.95, 95% CI
      1.08-8.04, P = 0.01). Thus the magnitude of HCV-RNA decreases at week 4
      correlated with treatment response. Significant differences in viral kinetics and
      cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV
      coinfection, which was independently associated with treatment failure.

PMID- 16792541
TI  - Interferon gamma-secreting HCV-specific CD8+ T cells in the liver of patients
      with chronic C hepatitis: relation to liver fibrosis--ANRS HC EP07 study.
AB  - Little is known about the role of specific hepatitis C virus (HCV) CD8+ T cells
      in liver damage, especially for the progression of fibrosis, during the highly
      variable course of chronic C hepatitis. The aim of this study was to investigate
      the presence of HCV-specific CD8+ T cells in the liver of patients with chronic C
      hepatitis and to examine their clinical significance by relating the response to
      liver fibrosis and progression rate, serum viral load, serum aminotransferase
      levels, inflammatory activity and in situ characteristics of the intrahepatic
      infiltrate. Fifteen patients were prospectively included in the study.
      Intrahepatic lymphocytes were tested for interferon gamma (IFNg) production in
      response to HCV class I-restricted epitopic peptides using enzyme-linked
      immunospot analysis. Liver biopsy samples were evaluated for fibrosis, fibrosis
      progression rate, activity, and in situ number of CD8+ cytotoxic lymphocytes and
      apoptotic cells. An IFNg-specific CD8+ T-cell response was detected in the liver
      samples of 47% of patients which was significantly related to a lower stage of
      fibrosis (P = 0.02) and a lower progression rate of fibrosis (P = 0.01). It was
      neither related to the number of cytotoxic lymphocytes infiltrating the liver nor
      to hepatocyte apoptosis. In conclusion, our results indicate that the presence of
      HCV-specific IFNg-secreting T cells in the liver of patients with chronic C
      hepatitis is associated with low liver fibrosis and fibrosis progression rate,
      suggesting that these IFNg-secreting T cells might limit the progression of liver
      damage.

PMID- 16792542
TI  - Lifestyle changes and beliefs regarding disease severity in patients with chronic
      hepatitis C.
AB  - The aim of this prospective study was to investigate beliefs regarding disease
      severity and lifestyle changes following hepatitis C diagnosis in patients with
      chronic hepatitis C (CHC). One hundred and eighty-five consecutive CHC patients
      were interviewed by means of self-questionnaires exploring several aspects of
      their disease. Most patients (93%) identified cirrhosis and liver cancer as the
      two main complications of CHC. More than half of patients (59%) thought that CHC
      was always associated with a fatal outcome whereas 3% thought that they would
      stay healthy. HCV viral load was the most commonly reported factor associated
      with disease severity. Sex life changes were reported by 107 patients (58%)
      whereas dietary intake changes were reported by 88 patients (48%). In
      multivariate analysis, changes in sex life were associated with male gender [odds
      ratio (OR): 2.57, 95% CI: 1.30-5.08, P < 0.007], perceived disease severity (OR:
      1.02, 95% CI: 1.00-1.03, P < 0.03) and anxiety (OR: 1.05, 95% CI: 1.01-1.08, P <
      0.003), whereas changes in dietary intake were associated with age (OR: 1.04, 95%
      CI: 1.02-1.08, P < 0.003) and anxiety (OR: 1.04, 95% CI: 1.01-1.08, P < 0.006).
      Our results show the considerable impact of CHC diagnosis on patients' lifestyle.
      They emphasize the need for improving CHC patient counselling in order to avoid
      unnecessary sex life and dietary intake changes.

PMID- 16792543
TI  - Selection of different 5' untranslated region hepatitis C virus variants during
      post-transfusion and post-transplantation infection.
AB  - BACKGROUND: Hepatitis C virus (HCV) translation is initiated in a cap-independent
      manner by an internal ribosome entry site (IRES) located within the 5'
      untranslated region (5'UTR). Sequence changes in this region could affect
      translation efficiency and presumably viral replication. AIM: To determine
      translation efficiency of 5'UTR variants developing during post-transfusion
      hepatitis C in two immunocompetent subjects and in two immunosuppressed liver
      recipients with recurrent HCV. METHODS: Sequential samples were screened for
      5'UTR changes by single-strand conformation polymorphism followed by cloning and
      sequencing whenever band pattern suggested sequence changes. 5'UTR variants were
      tested for IRES activity using a bicistronic dual luciferase expression plasmid
      transfected into HepG2 and Huh7 cell-lines. RESULTS: In the transfused patients,
      translation efficiency of 5'UTR variants from early post-transfusion samples was
      5.1- to 13.7-fold higher than that of predominant variants found in late follow
      up samples. Post-transplant variants in the other two patients had 2.6- to 5.9
      fold higher translation efficiency than those present only in pretransplant
      samples. CONCLUSION: In the immunocompetent host there may be selection of low
      translation efficiency HCV variants over the course of infection. However, in
      immunosuppressed subjects the opposite seems to be true as low translation
      efficiency variants are superseded by high translation efficiency variants.

PMID- 16792544
TI  - Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional
      cell recognition molecule that plays a critical role in cancer progression.
AB  - Emmprin (basigin, CD147) is a cell surface glycoprotein that belongs to the
      immunoglobulin superfamily. It is highly expressed on the surface of tumor cells
      and stimulates adjacent fibroblasts or tumor cells to produce matrix
      metalloproteinases. Moreover, it has recently been shown that emmprin also
      stimulates expression of vascular endothelial growth factor and hyaluronan, which
      leads to angiogenesis and anchorage-independent growth/multidrug resistance,
      respectively. These findings have made emmprin an important molecule in tumor
      progression and, thus, more attractive as a target for antitumor treatment.
      However, other functions of emmprin, including as an activator of T cells, a
      chaperone for monocarboxylate transporters, a receptor for cyclophilin A and a
      neural recognition molecule, are also being identified in physiological and
      pathological conditions. Therefore, it is essential to develop specific means to
      control particular functions of emmprin, for which elucidation of each mechanism
      is crucial. This review will discuss the role of emmprin in tumor progression and
      recent advances in the molecular mechanisms of diverse phenomena regulated by
      emmprin.

PMID- 16792545
TI  - Extracellular signal-regulated protein kinase is activated in cervical
      intraepithelial neoplasms but inactivated in invasive cervical carcinoma.
AB  - The extracellular signal-regulated protein kinase (ERK) signaling pathway has
      been reported to play important roles in cell growth in various neoplasms. The
      purpose of the present study was to immunohistochemically analyze the
      phosphorylation status (activity) of ERK in 24 cases of cervical carcinoma using
      an antiphosphorylated ERK antibody (alphap-ERK Ab) that specifically recognizes
      the phosphorylated form of ERK (p-ERK). In normal cervical epithelium, p-ERK was
      found to be confined to basal cells that were negative for Ki-67, suggesting that
      ERK was not activated in proliferating normal cervical epithelium. In cervical
      intraepithelial neoplasms (CIN), increased abnormal parabasal cells were positive
      for both p-ERK and Ki-67, suggesting that ERK activation in CIN may be involved
      in tumor cell proliferation. In contrast, it was found that, in invasive cervical
      carcinomas, almost all the carcinoma cells were positive for Ki-67 but negative
      for p-ERK, suggesting that, in contrast to many other types of cancers, the ERK
      signaling pathway is downregulated in invasive cervical carcinoma. These findings
      suggest that the phosphorylation status of ERK differs between CIN and invasive
      carcinomas, and that downregulation of the ERK signaling pathway may contribute
      to transformation of CIN to invasive cervical carcinomas.

PMID- 16792546
TI  - Expression of serine threonine kinase 15 is associated with poor differentiation
      in lung squamous cell carcinoma and adenocarcinoma.
AB  - Serine threonine kinase 15 (STK15, also named BTAK, Aurora-A, aurora-2, or AIKI)
      is a type of mitotic kinase. The overexpression of STK15 is significantly
      associated with carcinogenesis in many tumors. The purpose of the present study
      was to investigate the expression of STK15 in lung squamous cell carcinoma and
      adenocarcinoma and analyze the correlation between STK15 expression and
      clinicopathological factors. The expression patterns of STK15 were examined by
      immunohistochemistry in 80 lung squamous cell carcinomas and adenocarcinomas and
      20 normal lung tissues. The protein and mRNA expression of STK15 were evaluated
      by western blot and reverse transcription-polymerase chain reaction (RT-PCR) in
      40 lung cancer samples and corresponding normal lung tissues.
      Immunohistochemically, the positivity of STK15 expression was 68.75% (55/80). The
      STK15 expression was significantly higher in poorly differentiated lung cancers
      than in well-differentiated or moderately differentiated lung cancers (P =
      0.011). Western blot and RT-PCR showed that the protein and mRNA expression of
      STK15 were correlated (P = 0.044) and significantly higher in tumors than in
      corresponding normal lung tissues (P < 0.05). These results indicate that the
      overexpression of STK15 contributes to the carcinogenesis and de-differentiation
      of lung cancers.

PMID- 16792547
TI  - Local balance of transforming growth factor-beta1 secreted from
      cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal
      fibroblasts is a factor involved in invasion of cholangiocarcinoma.
AB  - Tumor-stromal interactions are important for the progression of malignant tumors.
      The purpose of the present study was to examine interactions of
      cholangiocarcinoma (CC) cells and stromal fibroblasts with respect to stromal
      derived factor-1 (SDF-1) and transforming growth factor (TGF)-beta1. Two cell
      lines of CC (HuCCT-1 and CCKS-1) and WI-38 fibroblast cell line were used for
      cell culture, and 12 CC tissue specimens for immunohistochemical studies.
      Invasion of CC cells was increased significantly by the supernatant from
      fibroblast cultures, but not by the supernatant from fibroblasts cocultured with
      CC cells. Expression of SDF-1 in cultured fibroblasts was downregulated by TGF
      beta1 treatment, and coculture with CC cells and anti-TGF-beta1 neutralizing
      antibody restored the decreased SDF-1 expression, suggesting that TGF-beta1
      secreted from CC cells might have reduced the expression of SDF-1 by fibroblasts
      and might have reduced the increased invasion of CC cells induced by the
      supernatant from fibroblasts. Immunohistochemical expression of TGF-beta1 in CC
      cells was focal or negative and that of SDF-1 was evident in stromal fibroblasts
      at the invasive front of CC. In conclusion, local mutual influence of TGF-beta1
      secreted from carcinoma cells and SDF-1 expressed by stromal fibroblasts may be
      involved in invasion of CC cells.

PMID- 16792548
TI  - Histopathological approach to prostatic contour alterations with the concept of
      left-right asymmetry.
AB  - It has been suggested that prostate cancer spread has predictable patterns, with
      prostate cancers known to affect the prostatic contours. However, few systematic
      investigations have documented the associated contour alterations, especially at
      a clinically localized stage. The purpose of the present paper was to objectively
      evaluate prostatic contour alterations based on left-right asymmetry, and analyze
      the histopathological features and prognostic impact. One hundred and sixty-two
      asymmetrical contours with left-right asymmetry in the length >or=10%, and 278
      cancer foci were observed in 114 radical prostatectomy specimens. Of the
      asymmetrical contours, 55 (34%) were caused by cancer, and of the cancer foci, 55
      (20%) generated asymmetrical contours. Cancer-associated asymmetries showed
      significant correlations with aggressive behaviors such as cancer volume, Gleason
      score, positive surgical margin, and extraprostatic extension, although these
      were not significantly associated with unfavorable prognosis. The authors present
      basic data relating to altered prostatic contours, such as spatial distribution
      and causative pathological conditions. Clinicopathological characteristics
      concerning cancer-associated contour alterations, are also presented in detail.

PMID- 16792549
TI  - Jugular foramen chordoid meningioma.
AB  - Chordoid meningioma (CM) is a rare histological variant of meningioma and is
      classified as an atypical meningioma on pattern alone. Herein is described the
      first case of CM occurring in the jugular foramen. The patient was a 45-year-old
      woman with a 2 year history of progressive right hearing loss. Magnetic resonance
      imaging (MRI) demonstrated a large, dumbbell-shaped, homogenously gadolinium
      enhanced mass in the right jugular foramen, extending medially to the
      cerebellopontine angle and caudally into the upper carotid space. Angiographic
      findings supported a diagnosis of schwannoma. Intraoperatively, the tumor
      appeared to involve the right glossopharyngeal nerve completely and the vagus
      nerve incompletely, and was incompletely resected. Microscopically, the tumor
      consisted predominantly of cords and nests of medium-sized cells with bland
      cytological features, surrounded by a pale basophilic mucin.
      Immunohistochemically, the tumor cells demonstrated reactivity for epithelial
      membrane antigen (membranous) and vimentin, with negative staining for S-100
      protein, cytokeratin, CD34, glial fibrillary acidic protein (GFAP),
      synaptophysin, and chromogranin A. Based on the chordoid histology, an organoid
      lobular arrangement of the tumor cells, and the location of the tumor (jugular
      foramen), the differential diagnosis included not only a chordoma but also a
      paraganglioma (glomus jugulare tumor). Histological identification of typical
      meningotheliomatous areas, plus selective immunohistochemical panel, is important
      to establish the correct diagnosis.

PMID- 16792550
TI  - Primary pulmonary choriocarcinoma combined with adenocarcinoma.
AB  - An extremely rare autopsy case of primary pulmonary choriocarcinoma combined with
      adenocarcinomatous components in a 77-year-old Japanese man is described. The
      patient died of rapidly progressive respiratory dysfunction without ante-mortem
      diagnosis. Autopsy revealed necro-hemorrhagic areas of the primary lung tumor
      with a typical biphasic pattern of choriocarcinoma. Topographical analysis
      suggested that moderately to poorly differentiated adenocarcinoma components
      partially surrounded the choriocarcinomatous components. Moreover,
      dedifferentiated carcinomatous components were scattered next to both
      adenocarcinomatous and choriocarcinomatous areas, and a few cells of the
      dedifferentiated carcinomatous components had a similar immunoreaction to
      conventional adenocarcinomatous or choriocarcinomatous components, such as
      surfactant apoprotein A, placental alkaline phosphatase or beta-human chorionic
      gonadotropin. Additionally, epithelial membrane antigen-positive
      cytotrophoblastic cells were rarely found in choriocarcinomatous areas. The
      present case suggests that primary lung choriocarcinoma can occur closely related
      to conventional pulmonary adenocarcinoma, although collision tumor was not
      completely ruled out.

PMID- 16792551
TI  - Severe congestive heart failure with cardiac liver cirrhosis 10 years after
      orthotopic liver transplantation for familial amyloidotic polyneuropathy.
AB  - Reported herein is an autopsy case of familial amyloidotic polyneuropathy (FAP)
      with cardiac liver cirrhosis associated with amyloid cardiomyopathy after liver
      transplantation. At 47 years of age a Japanese woman with a transthyretin
      Val30Met mutation and sensorimotor polyneuropathy underwent liver
      transplantation; no postoperative deterioration related to the graft or
      polyneuropathy occurred. However, cardiovascular dysfunction associated with
      amyloid deposition gradually worsened. Pacemaker implantation and diuretics were
      ineffective against the heart failure; 10 years after transplantation the patient
      died. Autopsy revealed massive pleural and pericardial effusions and amyloid
      cardiomyopathy, especially in the right atrium and cardiac conduction system.
      Amyloid deposition was slight in all organs except the heart, but liver cirrhosis
      with reversed lobulation and centrilobular hemorrhagic necrosis was prominent.
      There was no histological evidence for chronic liver graft rejection. These
      findings suggest that liver transplantation effectively stopped amyloid
      deposition and ameliorated clinical FAP symptoms but that amyloid cardiomyopathy
      after liver transplantation in advanced clinical stages may lead to severe
      congestive heart failure and cardiac liver cirrhosis.

PMID- 16792552
TI  - Carcinosarcoma of the liver producing granulocyte-colony stimulating factor.
AB  - An autopsy case of carcinosarcoma of the liver producing granulocyte-colony
      stimulating factor (G-CSF) is reported. The patient, a 74-year-old Japanese man,
      presented with multiple liver masses. His serum G-CSF was elevated to 286 pg/mL
      and a marked leukocytosis of 19 100/microL was observed. The patient had a
      rapidly aggravated clinical course and died 57 days after admission. Autopsy
      revealed a liver carcinosarcoma composed both of hepatocellular carcinoma (HCC)
      and sarcomatous elements immunoreactive with alpha-smooth muscle actin and
      desmin. Immunohistochemistry revealed positive staining of G-CSF in the cytoplasm
      of HCC, whereas none of the spindle cells was positively stained. Production of G
      CSF was also confirmed by enzyme-linked immunosorbent assay, using the frozen
      tumor tissue taken at the autopsy. Similar to the majority of G-CSF-producing
      tumors in the literature, only the epithelial elements of the present case were
      immunopositive for G-CSF. Although a monoclonal origin of carcinosarcomas has
      generally been proposed, heterologous differentiation from a single clone might
      lead to the production of G-CSF only in the epithelial element in the present
      case. It is suggested that G-CSF was associated with the high-grade
      transformation of the epithelial elements, as well as the reported phenomenon of
      conventional HCC producing G-CSF.

PMID- 16792553
TI  - Cardiac and neuromuscular implications in left ventricular hypertrabeculation/non
      compaction.

PMID- 16792555
TI  - Effects of variation at the ALDH2 locus on alcohol metabolism, sensitivity,
      consumption, and dependence in Europeans.
AB  - BACKGROUND: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene
      found in East Asian populations leads to the alcohol flush reaction and reduces
      alcohol consumption and risk of alcohol dependence (AD). We have tested whether
      other polymorphisms in the ALDH2 gene have similar effects in people of European
      ancestry. METHODS: Serial measurements of blood and breath alcohol, subjective
      intoxication, body sway, skin temperature, blood pressure, and pulse were
      obtained in 412 twins who took part in an alcohol challenge study. Participants
      provided data on alcohol reactions, alcohol consumption, and symptoms related to
      AD at the time of the study and subsequently. Haplotypes based on 5 single
      nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in
      the ALDH2 gene on alcohol metabolism and alcohol's effects. RESULTS: The typed
      SNPs were in strong linkage disequilibrium and 2 complementary haplotypes
      comprised 83% of those observed. Significant effects of ALDH2 haplotype were
      observed for breath alcohol concentration, with similar but smaller and
      nonsignificant effects on blood alcohol. Haplotype-related variation in responses
      to alcohol, and reported alcohol consumption, was small and not consistently in
      the direction predicted by the effects on alcohol concentrations. CONCLUSIONS:
      Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the
      data do not support the hypothesis that this leads to effects on alcohol
      sensitivity, consumption, or risk of dependence.

PMID- 16792556
TI  - Association between GABRA1 and drinking behaviors in the collaborative study on
      the genetics of alcoholism sample.
AB  - BACKGROUND: A wealth of literature supports the role of gamma-aminobutyric acid
      (GABA) in neurobiological pathways contributing to alcohol dependence and related
      phenotypes. Animal studies have consistently tied rodent homologs of the GABAA
      receptor genes on human chromosome 5q to alcohol-related behaviors; however,
      human studies have produced mixed results. Family-based association analyses
      previously conducted in the Collaborative Study on the Genetics of Alcoholism
      (COGA) sample yielded no evidence of association with Diagnostic and Statistical
      Manual of Mental Disorder-fourth edition (DSM-IV) alcohol dependence and these
      genes. As a follow-up to that study, we examined several alcohol-related
      behaviors in the COGA sample as follows: (1) a broader definition of alcohol
      dependence, including DSM-III-R symptoms and Feighner criteria (referred to as
      COGA alcohol dependence); (2) withdrawal; (3) history of alcohol-induced
      blackouts; (4) level of response to alcohol; (5) age of onset of regular
      drinking; and (6) age at first drunkenness. METHODS: Family-based association
      tests were conducted, using multiple single-nucleotide polymorphisms (SNPs) in
      each of the 4 GABAA receptor genes on chromosome 5q. RESULTS: In GABRA1, we found
      evidence of association with several of the drinking behavior phenotypes,
      including COGA alcohol dependence, history of blackouts, age at first
      drunkenness, and level of response to alcohol. We did not find consistent
      evidence of association with the remaining genes and any of the phenotypes.
      CONCLUSIONS: We found evidence for association between GABRA1 and COGA alcohol
      dependence, history of blackouts, age at first drunkenness, and level of response
      to alcohol. These analyses suggest that efforts to characterize genetic
      contributions to alcohol dependence may benefit by examining alcohol-related
      behaviors in addition to clinical alcohol dependence diagnoses.

PMID- 16792558
TI  - Fatty acid ethyl ester effects on interleukin-2 production, cyclic AMP synthesis,
      and calcium influx in human mononuclear cells.
AB  - BACKGROUND: Fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites, are
      produced by the esterification of fatty acids and ethanol. Plasma and serum FAEE
      correlate linearly with blood ethanol levels and are present in organs most
      commonly damaged by ethanol abuse. Our previous studies have shown that there is
      significant synthesis of FAEE by human mononuclear cells within seconds of
      exposure to physiologic doses of ethanol. OBJECTIVES: We studied the effects of
      FAEE on selected early events of mononuclear cell activation that follow
      stimulation with phytohemagglutinin (PHA). Fatty acid ethyl esters induced
      changes in cytosolic free calcium ([Ca2+]) levels, the production and secretion
      of interleukin-2 (IL-2) by the cells, and intracellular cAMP concentrations.
      METHODS: A mononuclear fraction of human white blood cells (WBC) was incubated
      with physiologic doses of FAEE. For experiments involving IL-2 production and
      calcium influx, PHA-stimulated cells were incubated with 10, 25, 50, or 100
      microM ethyl oleate, a representative FAEE species, for 60 minutes. Interleukin-2
      was measured by enzyme immunometeric assay and maximum levels of Ca2+ were
      monitored by spectrofluorimetry. In other experiments, mononuclear cells were
      incubated with 10, 25, and 50 microM ethyl oleate for 0.08 to 120 minutes, and
      then the concentration of cAMP was determined by a cAMP competitive enzyme
      immunoassay system. RESULTS: Fatty acid ethyl esters inhibited the PHA-induced IL
      2 production and secretion in activated human mononuclear cells. Fatty acid ethyl
      esters also inhibited PHA-induced [Ca2+] influx into cells in a dose-dependent
      fashion. There was a rapid increase in the intracellular cAMP concentration of
      mononuclear cells induced by FAEE, with FAEE dose dependence. The cAMP
      concentration decreased as the incubation time with FAEE was increased.
      CONCLUSIONS: Fatty acid ethyl esters inhibited PHA-stimulated IL-2 production and
      Ca2+ influx into human mononuclear cells and elevated intracellular cAMP
      concentration. These changes in mononuclear cell signaling may be associated with
      the immunosuppression associated with alcohol abuse.

PMID- 16792557
TI  - QTL mapping for low-dose ethanol activation in the LXS recombinant inbred
      strains.
AB  - BACKGROUND: Most mouse quantitative trait loci (QTLs) for behavioral traits have
      been mapped using populations of mice derived from C57BL/6J (B6) and DBA/2J (D2).
      It is also important to identify QTLs for behavior in populations derived from
      other progenitors. We report results from QTL mapping for low-dose (ethanol)
      locomotor activation (LDA) using the recently developed LXS recombinant inbred
      (RI) strains, derived from Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS)
      progenitors. The LXS RI panel has additional genetic variation, and greater power
      due to a larger number of strains, compared with other RI panels and strain
      crosses. METHODS: Mice were tested using a 3-day protocol in which activity
      levels were monitored for 15 minutes each day. On day 1, baseline activity was
      recorded; on day 2, mice were injected with saline before testing; and on day 3,
      mice were injected with 1.8 g/kg ethanol and tested. RESULTS: Several suggestive
      QTLs were found, on chromosomes 2, 3, 4, 7, 8, 12, and 13; 3 of these QTLs were
      sex-specific. CONCLUSIONS: Two apparently novel LDA QTLs were identified, on
      chromosomes 4 and 8. The other QTLs appear to replicate previously identified LDA
      QTLs. These replicated QTLs will be pursued in subsequent studies designed to
      identify candidate genes.

PMID- 16792559
TI  - Increased plasma fatty acid ethyl ester levels following inhibition of oxidative
      metabolism of ethanol by 4-methylpyrazole treatment in human subjects.
AB  - BACKGROUND: Recent experimental evidence suggests that fatty acid ethyl esters
      (FAEE), nonoxidative metabolites of ethanol, mediate ethanol-induced organ
      damage. A direct association between pancreas-specific toxicity and increased
      levels of FAEE following inhibition of the oxidative metabolism of ethanol by 4
      methylpyrazole (4-MP) has previously been shown in studies with rats. METHODS: We
      obtained plasma samples from 32 healthy human volunteers who drank ethanol
      following 4-MP or placebo ingestion to determine whether in vivo inhibition of
      oxidative metabolism of ethanol causes a shift to nonoxidative metabolism of
      ethanol and the subsequent production of increased levels of FAEE. Plasma FAEE
      were isolated by solid-phase extraction and quantified by gas chromatography-mass
      spectrometry (GC-MS). RESULTS: Plasma FAEE levels in subjects receiving 4-MP
      treatment before ethanol consumption were elevated compared with plasma FAEE
      concentrations taken from control subjects who received a placebo before ethanol
      ingestion. Increased FAEE levels in the 4-MP treatment group occurred after peak
      blood ethanol, and peak FAEE levels were achieved. There was a correlation
      between the blood ethanol and the plasma FAEE levels, and the correlation
      persisted in the presence or absence of 4-MP. The peak FAEE values were greater
      in men than in women, with or without 4-MP treatment. CONCLUSIONS: Our results
      indicate that the in vivo inhibition of the oxidative metabolism of ethanol using
      4-MP results in an increased circulating concentration of FAEE, products of the
      nonoxidative metabolism of ethanol.

PMID- 16792560
TI  - Functional assessment of human alcohol dehydrogenase family in ethanol
      metabolism: significance of first-pass metabolism.
AB  - BACKGROUND: Alcohol dehydrogenase (ADH) is the principal enzyme responsible for
      ethanol metabolism in mammals. Human ADH constitutes a unique complex enzyme
      family with no equivalent counterpart in experimental rodents. This study was
      undertaken to quantitatively assess relative contributions of human ADH isozymes
      and allozymes to hepatic versus gastric metabolism of ethanol in the context of
      the entire family. METHODS: Kinetic parameters for ethanol oxidation for
      recombinant human class I ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, and ADH1C2;
      class II ADH2; class III ADH3; and class IV ADH4 were determined in 0.1 M sodium
      phosphate at pH 7.5 over a wide range of substrate concentrations in the presence
      of 0.5 mM NAD+. The composite numerical formulations for organ steady-state
      ethanol clearance were established by summing up the kinetic equations of
      constituent isozymes/allozymes with the assessed contents in livers and gastric
      mucosae with different genotypes. RESULTS: In ADH1B*1 individuals, ADH1B1 and
      ADH1C allozymes were found to be the major contributors to hepatic-alcohol
      clearance; ADH2 made a significant contribution only at high ethanol levels (> 20
      mM). ADH1B2 was the major hepatic contributor in ADH1B*2 individuals. ADH1C
      allozymes were the major contributor at low ethanol (< 2 mM), whereas ADH1B3 the
      major form at higher levels (> 10 mM) in ADH1B*3 individuals. For gastric mucosal
      alcohol clearance, the relative contributions of ADH1C allozymes and ADH4 were
      converse as ethanol concentration increased. It was assessed that livers with
      ADH1B*1 may eliminate approximately 95% or more of single-passed ethanol as
      inflow sinusoidal alcohol reaches approximately 1 mM and that stomachs with
      different ADH1C genotypes may remove 20% to 30% of single-passed alcohol at the
      similar level in mucosal cells. CONCLUSIONS: This work provides just a model, but
      a strong one, for quantitative assessments of ethanol metabolism in the human
      liver and stomach. The results indicate that the hepatic-alcohol clearance of
      ADH1B*2 individuals is higher than that of the ADH1B*1 and those of the ADH1B*3
      versus the ADH1B*1 vary depending on sinusoidal ethanol levels. The maximal
      capacity for potential alcohol first-pass metabolism in the liver is greater than
      in the stomach.

PMID- 16792561
TI  - Striatal dopamine release and family history of alcoholism.
AB  - BACKGROUND: The offspring of alcohol-dependent individuals are at increased risk
      for alcoholism. The present study was designed to determine whether mesolimbic
      dopamine binding potential (BP), dopamine release, stress hormones, and
      subjective responses to intravenous amphetamine are different in nonalcoholic
      offspring from families with a history of alcohol dependence [family history
      positive (FHP)] than in nonalcoholic offspring without a family history of
      alcohol dependence [family history negative (FHN)]. METHODS: Participants were 41
      healthy men and women (11 FHP, 30 FHN; age range 18-29). After completing
      baseline psychiatric symptom and personality measures, striatal D2/D3 dopamine BP
      and dopamine release in response to an amphetamine challenge were measured with
      positron emission tomography (PET) using the D2/D3 dopamine (DA) receptor
      radioligand [11C]raclopride. Binding potential was defined as Bmax/KD, percent
      change in BP from baseline defined dopamine release. During the scans, subjects
      rated the degree to which they were experiencing each of 10 possible drug
      effects. Plasma cortisol and growth hormone (GH) were also measured at scheduled
      intervals during the scans. RESULTS: Neither baseline BP nor dopamine release
      differed by family history. Similarly, subjective responses to amphetamine did
      not differ by a family history of alcoholism. Although both cortisol and GH
      increased following administration of amphetamine, these increases did not differ
      between family history groups. CONCLUSIONS: Using amphetamine to provoke
      mesolimbic dopamine, we did not show significant differences in dopamine release,
      subjective responses, or stress hormone measures as a function of family history
      of alcoholism.

PMID- 16792562
TI  - Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol
      exposure and effect?
AB  - BACKGROUND: Biomarkers of fetal exposure to alcohol are important to establish so
      that early detection and intervention can be made on these infants to prevent
      undesirable outcomes. The aim of this study was to analyze long-chain fatty acid
      ethyl esters (FAEEs) in meconium as potential biomarkers of fetal alcohol
      exposure and effect. METHODS: Fatty acid ethyl esters were analyzed in the
      meconium of 124 singleton infants by positive chemical ionization gas
      chromatography/mass spectrometry (GC/MS) and correlated to maternal ethanol use.
      RESULTS: A total of 124 mother/infant dyads were enrolled in the study: 31 were
      in the control group and 93 were in the alcohol-exposed group. The incidence (28%
      vs 9.7%, p = 0.037) of ethyl linoleate detected in meconium was significantly
      higher in the alcohol-exposed groups than the control groups. Similarly, when the
      concentrations of ethyl linoleate in meconium were grouped (trichotomized), there
      was a significant linear by linear association between alcohol exposure and group
      concentrations of ethyl linoleate (p = 0.013). Furthermore, only alcohol-exposed
      infants were found in the group with the highest ethyl linoleate concentration.
      The sensitivity of ethyl linoleate in detecting prenatal alcohol exposure was
      only 26.9%, and its specificity and positive predictive value were 96.8 and
      96.2%, respectively. There was no significant correlation between the
      concentration of ethyl linoleate in meconium and absolute alcohol consumed (oz)
      per drinking day across pregnancy, although a trend toward a positive correlation
      is seen at lower amounts of alcohol consumed. Among the polyunsaturated, long
      chain FAEEs, there was weak evidence that the incidence (21.5% vs 6.5%, p =
      0.057) and concentration (p = 0.064) of ethyl arachidonate (AA) were
      significantly higher in the alcohol-exposed groups than the control groups. Ethyl
      linolenate and ethyl docosahexanoate (DHA) in meconium were found only in the
      alcohol group, although not at statistically significant levels. Highly
      significant correlations were found among the concentrations of ethyl linoleate,
      ethyl linolenate, ethyl AA, and ethyl DHA in meconium (correlations ranged
      between rs = 0.203, p = 0.024; and rs = 0.594, p < 0.001). CONCLUSION: We
      conclude that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are
      biomarkers of high specificity for prenatal exposure to alcohol in newborn
      infants. We also propose that ethyl AA and DHA could be potential biomarkers of
      fetal alcohol effects on the developing fetal brain and should be investigated
      further.

PMID- 16792563
TI  - Detection of maternal alcohol use problems in the pediatric emergency department.
AB  - BACKGROUND: Maternal alcohol use problems may impact the health and well-being of
      children, but often remain unrecognized. Mothers of young children seldom seek
      outpatient care for themselves; thus, pediatric settings may present an
      opportunity for the detection of maternal alcohol use problems. This study
      examines the feasibility of screening for and prevalence of alcohol use problems
      in mothers of young children in the context of seeking pediatric emergency care.
      We also examined the relationship of maternal alcohol use problems with use of
      pediatric emergency care. METHODS: A total of 361 English-speaking mothers of
      children aged 7 and younger completed screening measures during their child's
      emergency care visit. TWEAK was used to screen for alcohol use problems. The
      screening survey also included information on children's health status and health
      care use, demographics, and the Center for Epidemiological Studies Depression
      Scale. RESULTS: Of the women approached, 90% agreed to complete the screening
      measure. On the basis of cutoff score of 2 or more, 7% of women had elevated
      TWEAK scores. Those women with a TWEAK score > 2 reported greater use of the
      pediatric emergency department (PED) than women scoring below the cutoff. On the
      basis of multivariate analyses, significant predictors of recent PED use included
      the presence of child chronic illness, younger maternal age, and TWEAK score.
      CONCLUSIONS: Screening for alcohol use problems among mothers of young children
      using the TWEAK appears to be feasible in a busy PED setting. The PED setting is
      promising for identifying risk drinking among women who may be less likely to be
      otherwise detected and for whom alcohol use may be impacting child outcomes.

PMID- 16792564
TI  - A Rasch model analysis of DSM-IV Alcohol abuse and dependence items in the
      National Epidemiological Survey on Alcohol and Related Conditions.
AB  - BACKGROUND: Questions persist about the diagnoses of alcohol abuse and alcohol
      dependence as defined by Diagnostic and Statistical Manual of Mental Disorder,
      Fourth Edition (DSM-IV). These questions center around the performance of
      individual alcohol use disorder (AUD) criteria and the nature of items used to
      assess them. In this study, we conduct in-depth analyses of interview items used
      to assess alcohol abuse and dependence. METHOD: We conducted Rasch model analyses
      of responses to 33 items assessing alcohol abuse and dependence criteria in the
      National Epidemiological Survey on Alcohol and Related Conditions, a nationally
      representative sample of 34,550 participants. We also examined whether items
      performed differentially by gender, race/ethnicity, age, education, and time
      frame of assessment (i.e., past year vs lifetime). RESULTS: A single latent
      dimension explained the vast majority of shared variance among the items. Abuse
      symptoms were not of consistently lower severity than dependence symptoms, and
      some were consistently prone to differential functioning across subgroups. Items
      related to tolerance also functioned differentially across subgroups especially
      in the comparison of past-year symptoms between young adults (ages 18-24) and
      older adults. Items differed widely in their empirically estimated severity, even
      when they were intended to assess the same DSM-IV criterion. CONCLUSIONS: The use
      of Rasch model analyses demonstrated the essential unidimensionality of AUD
      criteria and the lack of hierarchical ordering between abuse and dependence
      criteria, as well as potential sources of bias in the abuse diagnosis and the
      tolerance criterion. Results highlight that the prevalence and even the meaning
      of AUD criteria can differ substantially depending on the wording of items used
      to assess them. Implications for assessment of specific DSM criteria and for
      development of DSM-V are discussed.

PMID- 16792565
TI  - Novelty seeking as a moderator of familial risk for alcohol dependence.
AB  - BACKGROUND: Disinhibitory personality traits such as high novelty seeking (NS)
      are moderately heritable, and individuals with substance use disorders (SUDs)
      frequently exhibit such traits. However, recent studies have cast doubt on the
      supposition that such traits are true familial risk factors for SUD and
      particularly for alcohol dependence. Another possibility is that familial risk
      interacts with personality-associated risk, in which case the association between
      personality and familial risk might depend on sample composition, accounting for
      the lack of consensus among studies to date. We examined this possibility by
      analyzing the association between NS and alcohol dependence in individuals at
      intermediate and high levels of familial risk for alcohol dependence. METHODS:
      Data from the Collaborative Study on the Genetics of Alcoholism, a multisite
      family study, were examined. Subjects were 1,111 adult siblings of alcohol
      dependent index cases. Parental diagnoses of alcohol dependence and personality
      scores of NS from the Tridimensional Personality Questionnaire were used to
      predict alcohol dependence. RESULTS: A significant interaction between NS and
      familial risk for alcoholism was seen, such that NS was a significantly stronger
      predictor of alcohol dependence in subjects with one or more parents with alcohol
      dependence than in subjects without alcohol-dependent parents. CONCLUSIONS:
      Novelty seeking and familial risk interact so that the risk associated with high
      NS is magnified in families with parental alcohol dependence and NS is a
      moderator of familial risk. Accordingly, high NS is strongly associated with
      alcohol dependence in subjects with a parent diagnosed with alcohol dependence,
      but low NS may protect against the risk associated with familial alcoholism. This
      interaction may account for conflicting findings from studies that have examined
      this question previously.

PMID- 16792566
TI  - Changes in outlet densities affect violence rates.
AB  - BACKGROUND: Previous assessments of empirical relationships between alcohol
      outlets and rates of interpersonal violence have been conducted using cross
      sectional spatial data, data collected across small geographic units such as
      Census Tracts and zip codes. These assessments demonstrate that the availability
      of alcohol, measured by the number and types of alcohol outlets, is related to
      violence. These analyses have examined many potential confounds of the outlets
      violence connection (i.e., population and place characteristics) and
      statistically corrected for biases that arise in analyses of spatial data. The
      current study contributes the first observation of longitudinal relationships
      between alcohol outlets and violence. METHOD: The study examined longitudinal
      data from 581 consistently defined zip code areas represented in the California
      Index Locations Database, a geographic information system that coordinates
      population and ecological data with spatial attributes for areas across the
      state. Six years of data were collected on features of local populations (e.g.,
      household size) and places (e.g., retail markets) thought to be related to 1
      measure of violence (i.e., hospital discharges related to violent assaults).
      Assault rates were related to changes in population and place characteristics
      using random effects models with controls for spatial autocorrelation (n x t =
      3,486 observations). Changes in population and place characteristics of bordering
      (spatial lagged) areas were also considered. RESULTS: Lower median household
      income and greater percentages of minorities (African American, Hispanic, and
      Asian) were related to increased rates of violence. Ten percent increases in
      numbers of off-premise outlets and bars were related to 1.67 and 2.06% increases
      in violence rates across local and lagged spatial areas. Every 6 outlets
      accounted for 1 additional violent assault that resulted in at least 1 overnight
      stay at hospital. These effects increased with larger male populations, doubling
      with every 3% increase in percent males. CONCLUSION: Assault rates were most
      strongly related to median household incomes and minority populations within zip
      code areas. Controlling for changes in assault rates related to these measures,
      greater numbers of licensed alcohol retail establishments, especially bars and
      off-premise outlets, were related to rates of assault. Failures to regulate the
      growth in numbers of bars will increase rates of violence, especially in urban
      areas.

PMID- 16792567
TI  - Propensity of alcohol establishments to sell to obviously intoxicated patrons.
AB  - BACKGROUND: Although it is illegal to sell alcohol to an individual who appears
      obviously intoxicated, several recent studies show that the propensity of these
      types of sales is high. Our study further assesses the propensity of alcohol
      establishments to sell alcohol to obviously intoxicated patrons. In addition to
      providing more recent data (2001) on pseudo-intoxicated purchase attempts at
      Midwestern on-premise establishments, our study examines the association between
      establishment policies/practices and the likelihood of sales to intoxicated
      patrons. METHOD: We hired professional actors to feign intoxication while
      attempting to purchase alcohol (pseudo-intoxicated patrons) at 231 bars and
      restaurants, and we conducted a phone survey of owners/managers of each
      establishment. Our dependent variable was purchase attempt outcome (alcohol sold
      vs not sold). Our independent variables included policies/practices of
      establishments and characteristics of buyers/servers, establishments, and
      neighborhoods. RESULTS: Pseudo-intoxicated patrons were able to purchase alcohol
      in 65% of their attempts. Multivariate analyses showed the following: (1)
      compared with establishments with beer- and/or wine-only licenses, establishments
      with full liquor licenses were less likely to sell to intoxicated patrons; (2)
      establishments with average length of employment among managers of at least 1
      year were more likely to sell to obviously intoxicated patrons; and (3)
      establishments that held staff meetings at least once a month were less likely to
      sell to obviously intoxicated patrons. Neighborhood characteristics were not
      associated with our outcome in multivariate analyses. CONCLUSIONS: Our findings
      provide increased evidence of the need to address the illegal sale of alcohol to
      intoxicated patrons, particularly given that increased intoxication levels among
      patrons resulting from these types of sales can lead to alcohol-related problems.

PMID- 16792568
TI  - Acute alcohol intoxication suppresses the interleukin 23 response to Klebsiella
      pneumoniae infection.
AB  - BACKGROUND: Bacterial pneumonia is a widely recognized infection in the alcohol
      abusing patient. Interleukin 23 (IL-23) is a recently described cytokine critical
      for IL-17 induction and host survival during Klebsiella pneumoniae infection, a
      pulmonary pathogen commonly seen in alcoholics. We investigated the effect of
      acute alcohol intoxication on the IL-23 response to this infection. METHODS: Male
      C57BL/6 mice were given an intraperitoneal injection of ethanol (3.0 g/kg) or
      phosphate-buffered saline (PBS) 30 minutes before infection. Alveolar macrophages
      (AM) were cultured with bacteria in ethanol (0, 50, and 100 mM) to determine
      alcohol's effect on AM IL-23 expression, the bioactivity of which was determined
      by splenocyte IL-17 inducing activity. The role of IL-10 in alcohol-mediated
      suppression of AM IL-23 p19 mRNA expression was assessed using wild-type (WT) and
      IL-10 knock-out (KO) mice. Efficacy of AM pretreatment with interferon gamma (IFN
      gamma) on IL-23 expression before ethanol exposure and infection was evaluated.
      RESULTS: In vivo, acute intoxication suppresses the lung and bronchoalveolar
      lavage cell IL-23 response to pathogen. This effect was confirmed in vitro as
      ethanol dose-dependently inhibits AM IL-23 during infection. Acute intoxication
      increases lung and BAL cell IL-10 mRNA expression 2 hours after in vivo infection
      and, in vitro, recombinant IL-10 inhibits AM IL-23 expression. However, alcohol
      impairs IL-23 similarly in AM harvested from both WT and IL-10 KO mice.
      Interferon gamma pretreatment strongly inhibits AM IL-23 production in both the
      presence and absence of alcohol. CONCLUSIONS: Acute alcohol intoxication inhibits
      the pulmonary IL-23 response to K. pneumoniae infection both in vivo and in
      vitro, an effect independent of IL-10 induction. Interferon gamma priming
      antagonizes IL-23 and is, therefore, not likely to be a useful adjuvant therapy
      in restoring IL-23/IL-17 responses during infection and intoxication.

PMID- 16792569
TI  - Chronic ethanol treatment impairs Rac and Cdc42 activation in rat hepatocytes.
AB  - BACKGROUND: The effects of chronic ethanol feeding on rat hepatocytes have been
      shown to include impaired cell-extracellular matrix (ECM) adhesion events, such
      as decreased attachment and spreading as well as increased integrin-actin
      cytoskeleton association. These results, observed previously by this laboratory,
      are highly suggestive of impaired actin cytoskeleton reorganization, an event
      mediated by differential activation of the Rho family GTPases Rac, Cdc42, and
      RhoA. Therefore, the purpose of this study was to examine the effects of chronic
      ethanol administration on these GTPases. METHODS: Male Wistar rats were pair-fed
      4 to 5 weeks with a liquid diet containing either ethanol (as 36% of total
      calories) or isocaloric carbohydrate. Hepatocytes were isolated and plated on
      collagen IV up to 24 hours. At specific times, the hepatocytes were lysed and
      these lysates were analyzed for RhoA, Cdc42, and Rac activation. RESULTS: In
      freshly isolated hepatocytes from ethanol-fed rats, the GTP-bound (active) forms
      of Rac and Cdc42 were significantly decreased compared with pair-fed control
      rats, while the GTP-bound form of RhoA was not significantly altered. These
      ethanol-induced impairments in Rac and Cdc42 activation persisted even after
      plating the hepatocytes on collagen IV. Additionally, chronic ethanol treatment
      did not directly affect GTP binding of Cdc42 and Rac, as incorporation of
      GTPgammaS was not affected. CONCLUSIONS: Chronic ethanol administration
      selectively impairs Rac and Cdc42 activation in rat hepatocytes. As activation of
      these 2 GTPases is crucial for efficient cell attachment and spreading on ECM
      substrates, the results from this study suggest that the ethanol-induced
      impairments in Rac and Cdc42 activation are responsible for the impaired
      hepatocyte-ECM adhesion events observed previously by our laboratory.
      Furthermore, these results raise the intriguing possibility that these GTPases
      are involved in other ethanol-induced functional impairments, such as protein
      trafficking and receptor-mediated endocytosis.

PMID- 16792570
TI  - Disruptions in sleep time and sleep architecture in a mouse model of repeated
      ethanol withdrawal.
AB  - BACKGROUND: Insomnia and other sleep difficulties are perhaps the most common and
      enduring symptoms reported by alcoholics undergoing detoxification, especially
      those alcoholics with a history of multiple detoxifications. While some studies
      have reported sleep disruptions in animal models after chronic ethanol exposure,
      the reports are inconsistent and few address sleep architecture across repeated
      ethanol exposures and withdrawals. The present study evaluated sleep time and
      architecture in a well-characterized mouse model of repeated chronic ethanol
      exposure and withdrawal. METHODS: C57BL6/J mice were fitted with electrodes in
      frontal cortex, hippocampus, and nuchal muscle for collection of continuous
      electroencephalogram (EEG)/electromyogram (EMG) data. Baseline data were
      collected, after which mice received 4 cycles of 16-hour exposure to alcohol
      (ethanol: EtOH) vapor separated by 8-hour periods of withdrawal or similar
      handling in the absence of EtOH vapor. Ethanol-exposed mice attained a blood
      ethanol concentration of 165 mg%. Upon completion of vapor exposure, EEG/EMG data
      were again collected across 4 days of acute withdrawal. Data were subjected to
      automated analyses classifying 10-second epochs into wake, non-rapid eye movement
      (REM) sleep, or REM sleep states. RESULTS: Mice in withdrawal after chronic EtOH
      exposure showed profound disruptions in the total time asleep, across the acute
      withdrawal period. Sleep architecture, the composition of sleep, was also
      disrupted with a reduction in non-REM sleep concomitant with a profound increase
      in REM sleep. While altered sleep time and non-REM sleep loss resolved by the
      fourth day of withdrawal, the increase in REM sleep ("REM rebound") persisted.
      CONCLUSIONS: These results mirror those reported for the human alcoholic and
      demonstrate that EtOH withdrawal-induced sleep disruptions are evident in this
      mouse model of alcohol withdrawal-induced sensitization. This mouse model may
      provide mechanisms to investigate fully the high correlation between unremitting
      sleep problems and increased risk of relapse documented clinically.

PMID- 16792571
TI  - Behavioral interaction between nicotine and ethanol: possible modulation by mouse
      cerebellar glutamate.
AB  - BACKGROUND: Epidemiological studies show that people who drink alcoholic
      beverages also smoke cigarettes and vice versa. Furthermore, animal studies
      provide circumstantial evidence for ethanol and nicotine interaction. Previously,
      we demonstrated that intracerebellar nicotine attenuates ethanol ataxia. This
      study investigated the possible role of glutamate in modulating the interaction
      of nicotine and ethanol. METHODS: Glutamate drugs N-methyl-d-aspartate (NMDA) and
      (+)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA) as
      well as their antagonists were directly microinfused into the cerebellum of CD-1
      male mice to evaluate their effect on ethanol (2 g/kg i.p.) ataxia. Drug
      microinfusions were made via stereotaxically implanted stainless-steel guide
      cannulas. Rotorod was used to evaluate the ataxic response of ethanol. RESULTS:
      Microinfusion of nicotine (0.3125, 1.25, 5 ng) significantly attenuated ethanol
      ataxia dose-dependently, confirming the functional interaction between nicotine
      and ethanol as reported earlier. Intracerebellar pretreatment with hexamethonium,
      a nicotinic receptor (nAChR) antagonist, significantly blocked nicotine-induced
      attenuation of ethanol ataxia suggesting participation of nAChRs. When ethanol
      was injected before nicotine microinfusion, nicotine failed to attenuate ethanol
      ataxia, indicating the critical importance of initial activation of nAChRs by
      nicotine. Intracerebellar microinfusion of NMDA (30, 60, 125 ng) and its
      antagonist, (+)-MK-801 (50, 100, 200 ng), significantly increased and decreased,
      respectively, the nicotine-induced attenuation of ethanol ataxia in a dose
      related manner, suggesting participation of the NMDA receptor. Similarly,
      intracerebellar microinfusion of AMPA (7.5, 15, 30 ng) and its antagonist, nitro 
      2, 3-dioxobenzoquinoxaline-sulfonamide (NBQX; 25, 50, 100 ng), significantly
      increased and decreased, respectively, the nicotine-induced attenuation of
      ethanol ataxia in a dose-dependent manner. This suggests participation of the
      AMPA receptor and further supports involvement of the glutamate system in the
      ethanol-nicotine interaction. Intracerebellar nicotine failed to attenuate sodium
      pentobarbital (25 mg/kg i.p.) ataxia, suggesting the relative specificity of the
      nicotine-ethanol interaction. CONCLUSIONS: The results suggested that glutamate
      modulates the functional interaction between nicotine and ethanol because NMDA
      and AMPA enhanced the nicotine-induced attenuation of ethanol ataxia, whereas (+)
      MK-801 and NBQX reduced the attenuation.

PMID- 16792572
TI  - Longitudinal brain magnetic resonance imaging study of the alcohol-preferring
      rat. Part I: adult brain growth.
AB  - BACKGROUND: The alcohol-preferring (P) rat, a Wistar strain selectively bred to
      consume large amounts of alcohol voluntarily, has been used as an animal model of
      human alcoholism for 3 decades. Heretofore, knowledge about brain morphology has
      been confined to postmortem examination. Quantitative neuroimaging procedures
      make it feasible to examine the potential longitudinal effects of alcohol
      exposure in vivo, while controlling modifying factors, such as age, nutrition,
      and exercise. To date, few imaging studies have considered what morphological
      changes occur with age in the rodent brain, and none has systematically applied
      quantitative neuroimaging approaches to measure volume changes in regional brain
      structures over extended periods in the adult rat. METHODS: We used structural
      magnetic resonance imaging (MRI) in a longitudinal design to examine 2 cohorts of
      adult P rats, never exposed to alcohol: Cohort A included 8 rats, 7 of which
      survived the entire study (578 days) and 4 MRI sessions; Cohort B included 9
      rats, all of which survived the study (452 days) and 5 MRI sessions. RESULTS:
      Growth in whole-brain volume reached maximal levels by about 450 days of age,
      whereas body weight continued its gain without asymptote. Growth was not uniform
      across the brain structures measured. Over the initial 12 months of the study,
      the corpus callosum area expanded 36%, cerebellum 17%, and hippocampus 10%,
      whereas ventricle size was unchanged. Factors affecting growth rate estimates
      included litter effects, MR image signal-to-noise ratio, and measurement error.
      CONCLUSION: Unlike longitudinal human reports of regional volume declines in
      aging brain tissue, several brain structures in adult rats continued growing, and
      some growth patterns were litter-dependent. Determining normal regional growth
      patterns of brain and of the substantial variance exerted by litter differences,
      even in selectively bred rats, is essential for establishing baselines against
      which normal and aberrant dynamic changes can be detected in animal models of
      aging and disease.

PMID- 16792573
TI  - Longitudinal brain magnetic resonance imaging study of the alcohol-preferring
      rat. Part II: effects of voluntary chronic alcohol consumption.
AB  - BACKGROUND: Tracking the dynamic course of human alcoholism brain pathology can
      be accomplished only through naturalistic study and without opportunity for
      experimental manipulation. Development of an animal model of alcohol-induced
      brain damage, in which animals consume large amounts of alcohol following cycles
      of alcohol access and deprivation and are examined regularly with neuroimaging
      methods, would enable hypothesis testing focused on the degree, nature, and
      factors resulting in alcohol-induced brain damage and the prospects for recovery
      or relapse. METHODS: We report the results of longitudinal magnetic resonance
      imaging (MRI) studies of the effects of free-choice chronic alcohol intake on the
      brains of 2 cohorts of selectively bred alcohol-preferring (P) rats. In the
      companion paper, we described the MRI acquisition and analysis methods,
      delineation of brain regions, and growth patterns in total brain and selective
      structures of the control rats in the present study. Both cohorts were studied as
      adults for about 1 year and consumed high doses of alcohol for most of the study
      duration. The paradigm involved a 3-bottle choice with 0, 15 (or 20%), and 30%
      (or 40%) alcohol available in several different exposure schemes: continuous
      exposure, cycles of 2 weeks on followed by 2 weeks off alcohol, and binge
      drinking in the dark. RESULTS: Brain structures of the adult P rats in both the
      alcohol-exposed and the water control conditions showed significant growth, which
      was attenuated in a few measures in the alcohol-exposed groups. The region with
      the greatest demonstrable effect was the corpus callosum, measured on midsagittal
      images. CONCLUSION: The P rats showed an age-alcohol interaction different from
      humans, in that normal growth in selective brain regions that continues in adult
      rats was retarded.

PMID- 16792574
TI  - Abnormal transsulfuration and glutathione metabolism in the micropig model of
      alcoholic liver disease.
AB  - BACKGROUND: Alcoholic liver disease is associated with abnormalities of
      methionine metabolic enzymes that may contribute to glutathione depletion.
      Previously, we found that feeding micropigs a combination of ethanol with a
      folate-deficient diet resulted in the greatest decreases in S-adenosylmethionine
      and glutathione and increases in liver S-adenosylhomocysteine and oxidized
      disulfide glutathione. METHODS: To study the mechanisms of glutathione depletion,
      we analyzed the transcripts and activities of enzymes involved in its synthesis
      and metabolism in liver and plasma specimens that were available from the same
      micropigs that receive folate-sufficient or folate-depleted diets with or without
      40% of energy as ethanol for 14 weeks. RESULTS: Ethanol feeding, folate
      deficiency, or their combination decreased liver and plasma glutathione and the
      activities of hepatic copper-zinc superoxide dismutase and glutathione peroxidase
      and increased the activity of manganese superoxide dismutase and glutathione
      reductase. Hepatic levels of cysteine and taurine were unchanged while plasma
      cysteine was increased in the combined diet group. Cystathionine beta-synthase
      transcripts and activity were unaffected by ethanol feeding, while the activities
      of other transsulfuration enzymes involved in glutathione synthesis were
      increased. Glutathione transferase transcripts were increased 4-fold and its mean
      activity was increased by 34% in the combined ethanol and folate-deficient diet
      group, similar in magnitude to the observed 36% reduction in hepatic glutathione.
      CONCLUSIONS: Chronic ethanol feeding and folate deficiency acted individually or
      synergistically to affect methionine metabolism in the micropig by depleting
      glutathione pools and altering transcript expressions and activities of enzymes
      involved in its synthesis, utilization, and regeneration. The data suggest that
      the observed decrease in hepatic glutathione during ethanol feeding reflects its
      increased utilization to meet increased antioxidant demands, rather than
      reduction in its synthesis.

PMID- 16792575
TI  - Systemic and specific treatment for a global disease: allergen immunotherapy
      revisited.

PMID- 16792576
TI  - Mechanisms of allergen specific immunotherapy--T-cell tolerance and more.
AB  - Specific immune suppression and induction of tolerance are essential processes in
      the regulation and circumvention of immune defence. The balance between allergen
      specific T-regulatory (Treg) cells and T helper 2 cells appears to be decisive in
      the development of allergic and healthy immune response against allergens. Treg
      cells consistently represent the dominant subset specific for common
      environmental allergens in healthy individuals. In contrast, there is a high
      frequency of allergen-specific T helper 2 cells in allergic individuals. A
      decrease in interleukin (IL)-4, IL-5 and IL-13 production by allergen-specific
      CD4+ T cells due to the induction of peripheral T cell tolerance is the most
      essential step in allergen-specific immunotherapy (SIT). Suppressed proliferative
      and cytokine responses against the major allergens are induced by multiple
      suppressor factors, such as cytokines like IL-10 and transforming growth factor
      (TGF)-beta and cell surface molecules like cytotoxic T lymphocyte antigen-4,
      programmed death-1 and histamine receptor 2. There is considerable rationale for
      targeting T cells to increase efficacy of SIT. Such novel approaches include the
      use of modified allergens produced using recombinant DNA technology and adjuvants
      or additional drugs, which may increase the generation of allergen-specific
      peripheral tolerance. By the application of the recent knowledge in Treg cells
      and related mechanisms of peripheral tolerance, more rational and safer
      approaches are awaiting for the future of prevention and cure of allergic
      diseases.

PMID- 16792577
TI  - Specific oral tolerance induction in food allergy.
AB  - Specific oral tolerance in food allergy can be induced by oral administration of
      the offending food, starting with very low dosages, gradually increasing the
      daily dosage up to an amount equivalent to a usually relevant dose for daily
      intake, followed up by a daily maintenance dose. Unfortunately, the body of
      scientific evidence concerning specific oral tolerance induction (SOTI) is still
      rather poor. Following a couple of case reports, only a few studies on a limited
      number of patients including different allergens are available. So far, no
      placebo-controlled, long-term study has been published. Concerning the underlying
      immunological mechanism, a limited number of studies have reported on changes in
      antibody production, and more recently on the role of different T-cell
      populations. The individual pattern of clinical reaction during SOTI seems to
      vary considerably between patients and from allergen to allergen. Arguments in
      favour of SOTI are the safety for an inadvertent intake of the offending food and
      the increased quality of life. Arguments against SOTI are the necessity for a
      regular intake and possible long-term compliance problems. Indications to
      consider SOTI in the future might be (i) importance of the incriminated food for
      the individual nutritional regimen, (ii) avoidance of the corresponding food
      cannot be assured and (iii) persistent severe food allergy. However, before SOTI
      can be recommended for the daily praxis, more studies are warranted to clarify
      whether certain patients may profit from SOTI and to understand the underlying
      mechanism.

PMID- 16792578
TI  - Modulation of allergic immune responses by mucosal application of recombinant
      lactic acid bacteria producing the major birch pollen allergen Bet v 1.
AB  - BACKGROUND: Probiotic lactic acid bacteria (LAB) are able to modulate the host
      immune system and clinical trials have demonstrated that specific strains have
      the capacity to reduce allergic symptoms. Therefore, we aimed to evaluate the
      potential of recombinant LAB producing the major birch pollen allergen Bet v 1
      for mucosal vaccination against birch pollen allergy. METHODS: Recombinant Bet v
      1-producing Lactobacillus plantarum and Lactococcus lactis strains were
      constructed. Their immunogenicity was compared with purified Bet v 1 by
      subcutaneous immunization of mice. Intranasal application of the live recombinant
      strains was performed to test their immunomodulatory potency in a mouse model of
      birch pollen allergy. RESULTS: Bet v 1 produced by the LAB was recognized by
      monoclonal anti-Bet v 1 and IgE antibodies from birch pollen-allergic patients.
      Systemic immunization with the recombinant strains induced significantly lower
      IgG1/IgG2a ratios compared with purified Bet v 1. Intranasal pretreatment led to
      reduced allergen-specific IgE vs enhanced IgG2a levels and reduced interleukin
      (IL)-5 production of splenocytes in vitro, indicating a shift towards non
      allergic T-helper-1 (Th1) responses. Airway inflammation, i.e. eosinophils and IL
      5 in lung lavages, was reduced using either Bet v 1-producing or control strains.
      Allergen-specific secretory IgA responses were enhanced in lungs and intestines
      after pretreatment with only the Bet v 1-producing strains. CONCLUSIONS: Mucosal
      vaccination with live recombinant LAB, leading to a shift towards non-allergic
      immune responses along with enhanced allergen-specific mucosal IgA levels offers
      a promising approach to prevent systemic and local allergic immune responses.

PMID- 16792579
TI  - Common vaccine antigens inhibit allergen-induced sensitization and airway
      hyperresponsiveness in a murine model.
AB  - BACKGROUND: Co-vaccination with cellular pertussis vaccine down-regulates
      allergic sensitization to diphtheria and tetanus antigens. Using a murine model,
      we investigated whether vaccination with diphtheria/tetanus toxoids, administered
      separately or simultaneously with the whole cell vaccine of Bordetella pertussis,
      inhibits subsequent allergen-induced immune and inflammatory responses. METHODS:
      BALB/c-mice were vaccinated intracutaneously with a combination of diphtheria and
      tetanus toxoids or a combination of diphtheria and tetanus toxoids with a whole
      cell vaccine of B. pertussis (three times, days -21 to -7) prior to systemic
      sensitization (days 1-14) and repeated airway challenges (days 28-30) with
      ovalbumin. RESULTS: Compared with negative controls, systemic sensitization and
      airway allergen challenges induced high serum levels of allergen-specific IgE,
      predominant Th2-type cytokine production, airway inflammation and development of
      in vivo airway hyperreactivity. Vaccination with diphtheria and tetanus toxoids
      prior to sensitization suppressed IgE formation and development of eosinophilic
      airway inflammation. Co-vaccination with a whole cell pertussis vaccine inhibited
      allergen sensitization, airway inflammation and development of in vivo airway
      hyperreactivity. Prevention was due to an allergen-specific and general shift
      from a predominant Th2 towards a predominant Th1 immune response. CONCLUSION:
      Vaccination with diphtheria and tetanus toxoids alone or in combination with
      whole cell pertussis vaccine prior to allergen sensitization prevented allergen
      induced Th2 immune responses. Vaccine antigens may down-regulate allergic
      responses to a range of common allergens.

PMID- 16792580
TI  - Inhibition of type I allergic responses with nanogram doses of replicon-based DNA
      vaccines.
AB  - BACKGROUND: Allergic diseases have become a major public health problem in
      developed countries; yet, no reliable, safe and consistently effective treatment
      is available. DNA immunization has been shown to prevent and balance established
      allergic responses, however, the high dose of conventional DNA vaccines necessary
      for the induction of anti-allergic reactions and their poor immunogenicity in
      primates require the development of new allergy DNA vaccines. We evaluated
      protective and therapeutic effects of a Semliki-Forest Virus replicase-based vs a
      conventional DNA vaccine in BALB/c mice using the model allergen beta
      galactosidase. METHODS: Immunoglobulin (Ig)E suppression was determined by a
      basophil release assay as an in vitro correlate for allergen-specific
      crosslinking capacity of IgE reflecting the in vivo situation in an allergic
      individual. Th1 memory responses were measured by cytokine detection via enzyme
      linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT).
      RESULTS: Nanogram amounts of a replicase-based vector triggered a Th1 response
      comparable with that achieved with the injection of 20,000-times more copies of a
      conventional DNA plasmid, and induced IgE suppression in both a protective and a
      therapeutic setting. CONCLUSIONS: Replicase-based DNA vaccines fulfill the
      stringent criteria for an allergy DNA vaccine, i.e. low dose, strong Th1
      immunogenicity and memory, lack of 'therapy-induced' IgE production and
      anaphylactic side effects. Moreover, by triggering apoptosis in transfected
      cells, their unique 'immunize and disappear' feature minimizes the hypothetical
      risks of genomic integration or induction of autoimmunity.

PMID- 16792581
TI  - Engineered recombinant ovomucoid third domain can desensitize Balb/c mice of egg
      allergy.
AB  - The purpose of this study was to determine the in vivo desensitization efficacy
      of a hypoallergenic variant of egg white ovomucoid third domain (DIII) in Balb/c
      mice model. We mapped the immunodominant B-cell epitopes of ovomucoid in Balb/c
      mice. A hypoallergenic ovomucoid third domain (GMFA) mutant isoform having
      ablated allergenicity against egg allergic patient's sera was used to desensitize
      DIII-sensitized Balb/c mice by intraperitoneal injections. Ovomucoid DIII
      generated high levels of plasma histamine and specific immunoglobulin (Ig)E
      levels, and increased Th2 type cytokine (IL-4). On the other hand, the allergic
      response of mice desensitized with the GMFA was found to be significantly
      inhibited and abrogated by prevention of anaphylaxis reactions, low histamine
      levels and increased Th1-type cytokine (INF-gamma). It was found that
      significantly higher levels of IL-10 and IL-12 were secreted in the desensitized
      group. Desensitization with the GMFA antigen also suppressed synthesis of DIII
      specific-IgE levels and enhanced specific IgG2a and IgG levels compared with the
      group treated with the DIII antigen. The present results indicated that
      hyposensitization with the GMFA can desensitize or down-regulate the allergic
      response in Balb/c mice and this hypoallergenic variant of ovomucoid DIII can
      shift an ongoing allergen-specific Th2 response towards a Th1 skewed response.

PMID- 16792582
TI  - Steroid-sparing effect of subcutaneous SQ-standardised specific immunotherapy in
      moderate and severe house dust mite allergic asthmatics.
AB  - BACKGROUND: The present study evaluated the steroid-sparing effect of
      subcutaneous SQ-standardized specific immunotherapy (SIT) in moderate and severe
      house dust mite (HDM) allergic asthmatics. METHODS: Fifty-four adult asthmatics
      allergic to HDM requiring at least inhaled corticosteroids (ICS) doses equivalent
      to 500 microg fluticasone propionate daily were randomized to subcutaneous SIT or
      placebo injections for a period of 3 years. The minimum required ICS dose, 4 week
      diary of asthma symptom score, use of rescue medication, peak expiratory flow
      (PEF) measurements and visual analog scale for asthma symptoms were assessed
      before start of treatment and after 1, 2 and 3 years of treatment. RESULTS: In
      patients with moderate and severe asthma, the reduction in ICS was statistical
      significant after 2 years of treatment (P = 0.03) but not after 3 years. The
      median reductions were 82% and 42% after the third year for active and placebo
      respectively. In patients with moderate persistent asthma the reduction was
      statistical significant larger for those treated with SIT compared with placebo
      after year 2 and year 3. The median reductions after 3 years were 90% for SIT and
      42% for placebo (P = 0.04). Despite significant steroid reduction, there was no
      difference in asthma assessments between the two groups. No serious reactions
      related to SIT injections were seen. CONCLUSION: This study shows that SIT with a
      SQ-standardized HDM extract is safe. An ICS sparing effect was evident in
      patients with moderate persistent asthma.

PMID- 16792583
TI  - Randomized double-blind controlled study with sublingual carbamylated allergoid
      immunotherapy in mild rhinitis due to mites.
AB  - BACKGROUND: The clinical efficacy of sublingual immunotherapy (SLIT) in mite
      allergy and in mild disease is still a matter of debate, thus we performed a long
      term clinical trial. METHODS: The study was randomized, double-blind and placebo
      controlled. After a 1-year assessment, 68 patients with mild rhinitis
      with/without asthma due to mites were randomized to drugs + placebo or drugs +
      SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of
      monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0,
      absent to 3, severe) and drug consumption were assessed by diary card in the
      period November-February. Quality of life was assessed before and after each
      observation period and pharmaco-economy data were evaluated as well. RESULTS:
      Fifty-six patients completed the study. The rate of dropouts was similar in the
      two groups. No relevant side effect was reported. There was a significant
      reduction of total clinical scores (P < 0.05) in the active group vs placebo at
      the first year, but not at the second whereas nasal obstruction significantly
      improved in both years (P < 0.05). The reduction of drug intake score was
      significant only at the first year. No change was observed concerning most of the
      Short Form-36 items, because at baseline all patients displayed a normal profile.
      A significant change in SLIT group was seen for the item 'change in health
      status'. The need for extra visits was significantly lower in the active group
      (25%vs 43%). CONCLUSIONS: Sublingual immunotherapy was clinically effective and
      safe in mite-induced mild disease.

PMID- 16792584
TI  - Five-year follow-up on the PAT study: specific immunotherapy and long-term
      prevention of asthma in children.
AB  - BACKGROUND: A 3-year course of specific immunotherapy (SIT) in children with hay
      fever to grass and/or birch pollen significantly reduced the risk of developing
      asthma. To investigate the long-term preventive effect, we performed a follow up-
      2 years after termination of immunotherapy. METHODS: A total of 183 children,
      aged 6-14 years with grass and/or birch pollen allergy could be investigated 2
      years after discontinuation of SIT or no treatment. Conjunctival provocation
      tests (CPTs) and methacholine bronchial provocation tests were carried out during
      the season and winter after 5 years. The development of asthma was assessed by
      clinical evaluation. RESULTS: The significant improvement in hay fever and CPT
      results observed after 3 years of SIT persisted at the 5-year follow-up. No
      difference in bronchial responsiveness to methacholine was found after 5 years
      because of spontaneous improvement during the follow-up period in the control
      patients. The immunotherapy-treated children had significantly less asthma after
      5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3-5.7)] in favor of
      SIT for prevention of development of asthma and significantly less patients
      reported an increase in asthma scores (P < 0.01). CONCLUSION: Immunotherapy for 3
      years with standardized allergen extracts of grass and/or birch shows long-term
      clinical effect and preventive effect on development of asthma in children with
      seasonal rhinoconjunctivitis.

PMID- 16792585
TI  - European Polistes venom allergy.
AB  - The American Polistes species venom mixture--that of P. annularis, P. fuscatus,
      P. metricus and P. exclamans--was the only commercially available mixture for
      diagnosis and therapy until 1996. However, these species of Polistes are not
      present in Europe, where P. dominulus and P. gallicus and to a lesser extent P.
      nimphus are widespread. The aim of this study was to assess the allergenic
      differences among the commercial American mix, P. dominulus and P. gallicus venom
      in European patients and therefore to verify if this mixture is suitable for
      diagnosis in these patients. We carried out skin tests, radioallergosorbent tests
      (RAST) and RAST inhibition in Italian patients with adverse reactions to Polistes
      stings. RAST inhibition results demonstrated that cross-reactivity between the
      American and European species is only partial and that P. dominulus and P.
      gallicus venoms have exclusive allergens. Skin tests and direct RAST confirmed
      these results and also showed that European Polistes venom is more suitable than
      the American mix in Italian patients. Moreover, we found a high rate of cross
      reactivity between P. dominulus and P. gallicus. To conclude, P. dominulus and/or
      P. gallicus venoms are necessary for diagnosis and therefore in the therapy of
      European patients.

PMID- 16792586
TI  - Working towards healthy air in dwellings in Europe.
AB  - Poor indoor air quality has been implicated in the increase in allergic and
      respiratory diseases seen in industrialized countries in recent decades. Although
      air pollution in the workplace is well studied, much less is known about the
      consequences of poor air quality in homes. In an attempt to halt or slow down the
      increase in allergic and respiratory diseases, the European Federation of Allergy
      and Airways Diseases Patients Associations (EFA) carried out the EU-funded
      project entitled 'Towards Healthy Air in Dwellings in Europe' (THADE). The aims
      were to: compile an overview of evidence-based data about exposure to indoor air
      pollution and its health effects, particularly in relation to allergies, asthma
      and other respiratory diseases such as chronic obstructive pulmonary disease;
      review cost-effective measures and technology to improve indoor air quality;
      review legislation and guidelines on indoor air pollution; produce maps of
      pollutants in dwellings; and recommend an integrated strategy that defines
      appropriate indoor air quality policies for implementation in Europe. This paper
      summarizes the information about air quality in dwellings and indoor environment
      related diseases collected by expert consultants within the framework of THADE
      and terminates with recommendations for actions aimed at improving air quality in
      homes. The results of this project confirmed that air pollution in dwellings is a
      relevant health problem. It is a complex problem that must be addressed at
      European and international levels, and it involves the medical profession,
      scientific societies, patients' organizations, lawmakers, architects and the
      building industry. The complete THADE report is available at
      http://www.efanet.org/activities/documents/THADEReport.pdf.

PMID- 16792587
TI  - Are risk factors of childhood asthma predicting disease persistence in early
      adulthood different in the developing world?
AB  - BACKGROUND: Predictive factors of childhood asthma for favorable prognosis may
      differ between populations where a variety of genetic and environmental factors
      are present. OBJECTIVES: To document the factors predicting disease persistence
      in early adulthood in Turkey. METHODS: An outpatient cohort (n = 115) with a mean
      follow-up duration of 11.4 +/- 0.2 years was evaluated. Complete remission was
      defined as no asthma symptoms, no use of controller medication, no airflow
      limitation and no airway hyper-responsiveness, and clinical remission as no
      symptoms and no use of controller medication, within the past year. RESULTS: The
      mean ages during referral and at the final visit were 5.8 +/- 0.2 and 17.1 +/-
      0.2 years, respectively. Thirty-one (27%) were in complete remission, and a
      further 30 (26%) in clinical remission. In multivariate logistic models,
      diminished airflow [forced expiratory volume in 1 s (FEV1) < 80% vs > or = 80%]
      at the initial lung function test predicted current diminished airflow (8.422;
      2.202-32.206) (odds ratio; 95% confidence interval), and presence of obstructive
      pattern (FEV1/forced vital capacity (FVC) < 80% vs > or = 80%) predicted current
      obstructive pattern (29.333; 3.022-284.724). Furthermore, female gender appeared
      to predict persistence of asthma symptoms (3.330; 1.250-8.333) and absence of
      clinical remission (2.398; 1.038-5.254); eosinophilia predicted persistence of
      symptoms (4.271; 1.080-16.889) and presence of airway hyper-responsiveness
      (3.723; 1.129-12.278). CONCLUSIONS: Diminished airflow, female gender and
      eosinophilia appear to predict an adverse outcome of childhood asthma, supporting
      the concept that variability may exist between populations.

PMID- 16792589
TI  - Dexamethasone and IL-10 stimulate glucocorticoid-induced leucine zipper synthesis
      by human mast cells.
AB  - BACKGROUND: Glucocorticoids (GCs) decrease tissue mast cell (MC) number and
      prevent their activation via their high-affinity IgE receptor. Glucocorticoid
      induced leucine zipper (GILZ) is one of the GC-induced genes, which inhibits the
      functions of the transcriptional activators AP-1 and NF-kappaB. GILZ appears to
      be a critical actor in the anti-inflammatory and immunosuppressive effects of GCs
      in human T lymphocytes, macrophages and dendritic cells. AIMS OF THE STUDY: We
      investigated whether GILZ was produced by human MCs and whether GILZ synthesis
      was stimulated by GCs. We also investigated whether GILZ production was modulated
      by (i) IL-10, because of its common immunosuppressive properties with GCs, (ii)
      histamine because of its pro-inflammatory properties and (iii) IL-4 and IL-5
      because of their ability to favour MC survival and proliferation with SCF.
      METHODS: The human MC lines HMC-1 5C6 and LAD-2, and cord blood-derived MCs (CB
      MCs) were cultured alone or in the presence of GCs, IL-10, histamine, IL-4 or IL
      5. The expression of GILZ was evaluated by using RT-PCR, Western blotting or
      immunocytochemistry. RESULTS: We found that human MC lines and CB-MCs
      constitutively produce GILZ. We also show that GCs and IL-10 stimulate GILZ
      production by human MCs. Our present results indicate that histamine, IL-4 and IL
      5 alone or in combination with SCF do not downregulate GILZ production by MCs.
      CONCLUSIONS: These results show that GCs and IL-10 stimulate GILZ production by
      human MCs. As GILZ mediates anti-inflammatory effects of GCs in immune cells, we
      speculate that GILZ could account for the deactivation of MCs by GCs and IL-10.

PMID- 16792588
TI  - IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of
      eosinophilia in allergic inflammation.
AB  - BACKGROUND: Interleukin-25 (IL-25) is a novel T-helper-2 (Th2) cytokine of the IL
      17 family that plays a key role in allergic inflammation. Recent studies reported
      that over-expression of IL-25 in mouse induces eosinophilia. We investigated the
      effect of IL-25 on the expression of several adhesion molecules on human
      eosinophils and the underlying intracellular mechanisms. METHODS: Viability of
      eosinophils was measured by annexin V-fluorescein isothiocyanate (FITC) assay.
      Gene expression and surface expression of intercellular adhesion molecule (ICAM)
      1 (CD54), ICAM-3 (CD50), L-selectin (CD62L), leukocyte function-associated
      antigen (LFA-1) (CD11a/CD18) and very late antigen-4 (VLA-4, CD49d/CD29) on
      eosinophils were measured by reverse transcriptase-polymerase chain reaction (RT
      PCR) and flow cytometry, respectively. Adhesion of eosinophils to fibronectin was
      assessed using the fibronectin-coated insert system. RESULTS: Viability of
      eosinophils was significantly enhanced by IL-25 from 41% to 76% dose-dependently.
      IL-25 could significantly upregulate the surface expression of ICAM-1, but
      suppress those of ICAM-3 and L-selectin on eosinophils in a dose-dependent
      manner. Adhesion of eosinophils to fibronectin was also significantly enhanced by
      IL-25. Besides, pre-incubation with p38 mitogen-activated protein kinases (MAPK)
      inhibitor SB203580, C-Jun NH2-terminal protein kinases (JNK) inhibitor SP600125
      and proteosome inhibitor MG-132 could significantly restrain the effects of IL-25
      on surface expression of L-selectin, ICAM-1 and ICAM-3, respectively, and also on
      the adhesion of eosinophils onto fibronectin (all P < 0.05). CONCLUSIONS: Our
      findings suggest an essential role of IL-25 in enhancing survival and regulating
      surface expression of ICAM-1, ICAM-3 and L-selectin on human eosinophils through
      the activation of p38 MAPK, JNK and nuclear factor (NF)-kappaB pathways, thereby
      shedding light on the molecular mechanisms of IL-25-induced eosinophilia in
      allergic inflammation.

PMID- 16792590
TI  - HLA DRB1*15-DPB1*05 haplotype: a susceptible gene marker for isocyanate-induced
      occupational asthma?
AB  - BACKGROUND: There has been no study for evaluating the associations of human
      leukocyte antigen (HLA) class I and II alleles with toluene diisocyanate (TDI)
      induced asthma in an Asian population. OBJECTIVE: The aim of this study was to
      investigate a susceptible or protective marker of HLA class I and II alleles in
      TDI-induced asthma. METHODS: Fifty-five patients with TDI-induced asthma patients
      (group I) showing positive responses on TDI bronchoprovocation test, 47
      asymptomatic exposed subjects (group II) and 95 unexposed healthy nonatopic
      controls (group III) were enrolled in our study. HLA class I and II genotyping
      was done by the direct DNA sequencing method. RESULTS: The allelic frequency of
      C*09 (15.5%) was significantly higher in group I than in group III (6.8%, P =
      0.019), but this statistical significance disappeared after correction was made
      for multiple comparisons. On two-locus and three-locus haplotype analysis, the
      allelic frequency of HLA DRB1*15-DPB1*05 in group I (10.6%) was significantly
      higher than that of group II (0%, P = 0.001) and group III (2.5%, P = 0.003). The
      allelic frequencies of HLA A*02-DRB1*15, A*02-DQB1*06, B*62-C*09 and A*02-DRB1*15
      DQB1*06 were significantly higher in group I (8.5%, 10.3%, 8.2% and 6.8%,
      respectively) than those allelic frequencies of group III (1.3%, P = 0.002; 1.6%,
      P = 0.001; 0.6%, P < 0.0001; 0%, P < 0.0001, respectively). The allelic
      frequencies of HLA DQB1*06-DPB1*05 and DRB1*15-DQB1*06-DPB1*05 were significantly
      higher in group I (16.0% and 10.5%) than those in group II (2.5%, P = 0.001; 0%,
      P = 0.001), while the frequencies of DRB1*09-DPB1*05 and DRB1*09-DQB1*0303
      DPB1*05 were significantly lower in group I (0% and 0%) than those of group II
      (7.4%, P = 0.004; 7.5%, P = 0.004). These differences remained statistically
      significant even after the correction for multiple comparisons. CONCLUSIONS: The
      HLA haplotype DRB1*15-DPB1*05 can be a susceptibility gene marker for the
      development of TDI-induced asthma among the exposed workers in the Korean
      population.

PMID- 16792591
TI  - Rapeseed oil does not cause allergic reactions.

PMID- 16792592
TI  - Specific immunotherapy design questions.

PMID- 16792593
TI  - Predicting side-effects in venom immunotherapy by basophil activation?

PMID- 16792594
TI  - Specific immunotherapy among Italian specialists.

PMID- 16792595
TI  - The effect of specific immunotherapy on exhaled breath condensate nitrite levels.

PMID- 16792596
TI  - Tolerance to cooked egg in an egg allergic population.

PMID- 16792597
TI  - Beta-(1,3)-glucan on pillows.

PMID- 16792599
TI  - Sublingual immunotherapy in the treatment of children.
AB  - Children with controlled intermittent mild-to-moderate asthma, controlled
      rhinitis and a single sensitivity may be appropriate candidates for sublingual
      immunotherapy (SLIT). Positive effects of SLIT may depend on initiation in early
      childhood and a long duration of treatment. To ensure optimum compliance,
      sociological, economic and familial factors should also be taken in to
      consideration when prescribing SLIT. Evidence from recent long-term trials
      indicates that SLIT interfered with the atopic march and the allergic progression
      from rhinitis to asthma without any severe adverse side effects. Local immune
      response has been seen to be blunted with SLIT, which suggests that treatment has
      an immunomodulatory effect. In addition, it may also decrease the risk of new
      sensitizations. Ongoing developments in SLIT, particularly advances in dosing and
      new indications, such as food allergies, will increase the use of this treatment
      modality in children.

PMID- 16792600
TI  - Immunological mechanisms of sublingual immunotherapy.
AB  - Administration of allergen-specific immunotherapy by the oral route, sublingual
      immunotherapy (SLIT), has been shown to be effective, with an improved safety
      profile compared with subcutaneous administration. However, the precise
      mechanisms underlying the induction of immune tolerance by SLIT remain unclear.
      Contact of the allergen with the antigen-presenting cells in oral mucosa is
      likely to be critical. Mucosal Langerhans cells can capture the allergen and
      transport it to local lymph nodes, which may favour the induction of T
      lymphocytes that suppress the allergic response. In addition, the production of
      blocking IgG4 antibodies and the involvement of mucosal B cells appear to play a
      role. There is a growing evidence to support the role of regulatory T cells in
      controlling the development of asthma and allergic disease. Nevertheless, there
      remains a lack of firm evidence that SLIT induces regulatory T cells, although
      preliminary in vitro data suggest that SLIT may increase interleukin-10, which
      has a clear role in suppressing the allergic immune response. Further studies are
      required to determine the involvement of regulatory T cells, the role of
      different dendritic cell subsets, mucosal B cells as well as the potential use of
      adjuvants during SLIT.

PMID- 16792601
TI  - Sublingual immunotherapy: from biological extracts to recombinant allergens.
AB  - Sublingual vaccines based on biological extracts from various natural allergen
      sources are effective in the treatment of respiratory allergies. These vaccines
      comprise a complex mixture of proteins and glycoproteins that require dedicated
      standardization procedures to ensure batch-to-batch consistency. Because of the
      lack of correlation between the potency of an allergen extract and the quantity
      of major allergen content, standardization is achieved predominantly by
      determining the global IgE binding capacity of the extract in vitro. New
      proteomic technologies can be used to further characterize the most abundant
      proteins present in an extract. Second-generation sublingual vaccines based on
      recombinant allergens are under development. The aim is to produce molecularly
      defined vaccines that exhibit superior efficacy, while allowing for simplified
      immunization schedules. In this approach, recombinant DNA technology is used to
      express highly purified allergens in their native (i.e. wild-type) conformation.
      The recombinant allergens are then formulated with ad hoc adjuvants and/or
      mucoadhesive galenic excipients so that they specifically target oral Langerhans
      cells and induce allergen-specific regulatory T cells.

PMID- 16792602
TI  - Sublingual immunotherapy in the treatment of adult allergic rhinitis patients.
AB  - Sublingual immunotherapy (SLIT) was accepted for clinical use by the medical
      community only 15 years after the first controlled trial published. The
      acceptance of SLIT has been driven by the evidence base of a large number of
      clinical trials confirming the efficacy and a recent meta-analysis study.
      Although SLIT is self-managed by the patient, this does not generate problems
      with compliance. The safety profile, assessed in clinical trials and
      postmarketing surveillance studies, is satisfactory with no reports of systemic
      adverse reactions. New data are available on the persisting, long-lasting effect
      of SLIT and on the association with the prevention of asthma in paediatric
      patients. However, there is only indirect evidence for such persistence and
      duration of effect in adult patients. Key priorities for further investigation
      are the mechanisms of action, the efficacy in asthma, the cost/effectiveness and
      the identification of those patients who will achieve the maximum benefit with
      SLIT.

PMID- 16792603
TI  - Sublingual immunotherapy: efficacy--methodology and outcome of clinical trials.
AB  - Using Medline we identified 39 placebo-controlled, double-blind sublingual
      immunotherapy (SLIT) studies providing symptom-medication score. These were
      retrospectively evaluated for evidence of clinical efficacy and quality of study
      presentation. Clinical efficacy was estimated according to statistical
      significance and graded as: unequivocal efficacy (statistically significant
      difference from placebo in both symptom and medication scores or the combined
      score), which was observed in 28% of studies, possible efficacy (significant
      improvement in either symptom or medication scores) seen in 33%, and no efficacy
      (no statistical difference between active treatment and the placebo group), as
      found in 38% of studies. Generally, studies were limited by the number of
      patients, showed a high frequency of withdrawals, a short duration of treatment,
      and insufficient data on randomization. The magnitude of efficacy additional to
      placebo treatment must be >20% in order to justify the treatment. This review
      concludes that future SLIT studies should be planned in accordance with
      international recommendations in order to be conclusive.

PMID- 16792604
TI  - Future developments in sublingual immunotherapy.
AB  - The increasing prevalence of allergic rhinitis and its progression to asthma has
      severe implications for patients and health care systems in many countries. An
      ideal therapy is one that is effective not only against symptoms but also towards
      the natural progression of the allergic disease. Immunotherapy is recognized to
      achieve both these aims. Administration of allergens by the sublingual route, a
      modality with a very low rate of systemic reactions, is widely considered a
      treatment of choice. However, if it is to be universally accepted, more
      developments are required. Although, it is effective against grass and other
      seasonal pollens, further controlled trials are needed to confirm its efficacy
      against perennial allergens. Additional studies, particularly in paediatric
      populations, are needed to confirm its long-term effects on disease progression.
      New vaccine developments, which take into account the increasing understanding of
      the underlying immune mechanisms and that exploit molecular engineering
      techniques will create allergens that are effective, stable, risk free and easy
      to administer.

PMID- 16792605
TI  - 'Do not attempt resuscitation' orders in the peri-operative period.

PMID- 16792606
TI  - Does the efficacy of supplemental oxygen for the prevention of postoperative
      nausea and vomiting depend on the measured outcome, observational period or site
      of surgery?
AB  - High intra-operative oxygen concentration reportedly reduces postoperative nausea
      and vomiting (PONV), but recent data are conflicting. Therefore, we tested
      whether the effectiveness of supplemental oxygen depends on the endpoint (nausea
      vs. vomiting), observation interval (early vs. late) or surgical field (abdominal
      vs. non-abdominal). We randomly assigned 560 adult patients undergoing various
      elective procedures with a PONV risk of at least 40% to intra-operative 80%
      (supplemental) or 30% oxygen (control). Potential confounding factors were
      similar between groups. Incidences of nausea were similar in the groups during
      early (12% (supplemental) vs. 10% (control), p = 0.43) and late intervals, 26%vs.
      20%, p = 0.09, as were the incidences of vomiting (early: 2%vs. 3%, p = 0.40;
      late: 8%vs. 9%, p = 0.75). Supplemental oxygen was no more effective at reducing
      PONV in abdominal (40%vs. 31%, p = 0.37) than in non-abdominal surgery (25%vs.
      21%, p = 0.368). Thus, supplemental oxygen was unable to reduce PONV independent
      of the endpoint, observational period or site of surgery.

PMID- 16792607
TI  - Paraesthesia during the needle-through-needle and the double segment technique
      for combined spinal epidural anaesthesia.
AB  - Paraesthesia during regional anaesthesia is an unpleasant sensation for patients
      and, more importantly, in some cases it is related to neurological injury.
      Relatively few studies have been conducted on the frequency of paraesthesia
      during combined spinal epidural anaesthesia. We compared two combined spinal
      epidural anaesthesia techniques: the needle-through-needle technique and the
      double segment technique in this respect. We randomly allocated 116 parturients
      undergoing elective Caesarean section to receive anaesthesia using one of these
      techniques. Both techniques were performed using a 27G pencil point needle, an
      18G Tuohy needle, and a 20G multiport epidural catheter from the same
      manufacturer. The overall frequency of paraesthesia was higher in the needle
      through-needle technique group (56.9% vs. 31.6%, p = 0.011). The frequency of
      paraesthesia at spinal needle insertion was 20.7% in the needle-through-needle
      technique group and 8.8% in the double segment technique group; whereas the
      frequency of paraesthesia at epidural catheter insertion was 46.6% in the needle
      through-needle technique group and 24.6% in the double segment technique group.

PMID- 16792608
TI  - The circulatory responses to fibreoptic intubation: a comparison of oral and
      nasal routes.
AB  - The circulatory responses to fibreoptic intubation under general anaesthesia were
      studied in 60 adult female patients who were randomly assigned to receive either
      the oral or nasal route for insertion. Non-invasive blood pressure and heart rate
      were recorded before anaesthesia induction (baseline values), immediately after
      anaesthesia induction (post-induction values), at intubation and every minute for
      a further 5 min. The product of heart rate and systolic blood pressure (rate
      pressure product) at every time point was also calculated. The results showed
      that both fibreoptic orotracheal intubation and fibreoptic nasotracheal
      intubation resulted in significant increases in blood pressure, heart rate and
      rate pressure product compared to baseline and post-induction values. The times
      required to reach the maximum values of systolic blood pressure and heart rate
      were significantly longer in the fibreoptic nasotracheal intubation group than in
      the fibreoptic orotracheal intubation group. There were no significant
      differences between the two groups in blood pressure, heart rate and rate
      pressure product at any measuring point, or in the maximum values during
      observation. The time required for recovery of systolic blood pressure to the
      post-induction value was not significantly different between the two groups, but
      the time required for recovery of heart rate to post-induction value was
      significantly longer in the fibreoptic orotracheal intubation group than in the
      fibreoptic nasotracheal intubation group. It was concluded that both fibreoptic
      orotracheal and fibreoptic nasotracheal intubations could cause a similar
      magnitude of circulatory responses in general anaesthetised, female adults, but
      the tachycardic response to fibreoptic orotracheal intubation lasted longer than
      that to fibreoptic nasotracheal intubation.

PMID- 16792609
TI  - Determination of the site of tracheal tube impingement during nasotracheal
      fibreoptic intubation.
AB  - This study examines the incidence and site of tracheal tube impingement during
      nasotracheal fibreoptic intubation, and the efficacy of anticlockwise tube
      rotation to overcome the problem. Forty-three patients underwent fibreoptic
      assisted nasotracheal intubation using a preformed nasal tube, and a second
      fibrescope was used to observe any obstruction to passage of the tracheal tube.
      Impingement occurred in 10 cases, with the most common site being the right
      arytenoid cartilage. Rotation resulted in successful intubation in all 10 cases,
      but proximal rotation did not always result in an equal degree of rotation at the
      tube tip. We conclude that the site of impingement for nasotracheal intubation
      with preformed nasal tubes is located at the posterior structures of the
      laryngeal inlet and that anticlockwise rotation is a simple and effective
      solution.

PMID- 16792610
TI  - Decision analysis in anaesthesia: a tool for developing and analysing clinical
      management plans.
AB  - Traditional medical decision making is unstructured and incorporates evidence
      haphazardly. I present a more structured approach based on decision analysis, a
      model that considers all relevant options and outcomes informed by evidence where
      appropriate. This method is useful both for planning clinical management and for
      analysing decisions already taken.

PMID- 16792611
TI  - The site of action of epidurally administered opioids and its relevance to
      postoperative pain management.
AB  - The use of epidurally administered opioids to control postoperative pain is a
      well established and widely accepted technique. However, despite this
      longstanding use, there is still an ongoing debate concerning the site of action
      of the opioids used. Some argue that analgesia is mediated by a spinal mechanism
      and others that a supraspinal mechanism is responsible. On close inspection of
      the evidence it becomes apparent that epidural opioids act predominantly spinally
      when administered as a bolus, and predominantly supraspinally when administered
      as a continuous infusion. A concentration of 10 microg x ml(-1) appears to be the
      threshold at which epidurally administered fentanyl can elicit segmental
      analgesia, a value which may have significant clinical applications. The evidence
      supporting a synergistic relationship between epidural opioids and local
      anaesthetics is weak and unsupported by a plausible physiological mechanism. Thus
      the 'threshold concentration' of approximately 10 microg x ml(-1) is unlikely to
      be lowered by co-administering opioids with local anaesthetics.

PMID- 16792612
TI  - Bonfils semirigid endoscope for guidance during percutaneous tracheostomy.
AB  - We report on the use of the Bonfils semirigid scope for endoscopic guidance
      during percutaneous dilational tracheostomy. Forty patients requiring
      percutaneous dilational tracheostomy on the General or Neurosurgical Intensive
      Care Unit were enrolled in this study. We used the '45 degree curved distal tip'
      scope in the first 15 patients, evaluating its ease of use, optical quality of
      focus and image resolution as well as light intensity on a 10-point scale. We
      evaluated straight and curved versions of it in another 15 and 10 patients,
      respectively. We examined the impact on ventilation and cardiovascular
      parameters. In all patients (n = 40) visualisation of the procedure was
      satisfactory. There were no clinically significant changes in ventilatory or
      cardiovascular parameters. The image quality for most patients received a score
      of 7-10. The Bonfils scope provides a practical alternative to flexible
      bronchoscopes in this setting.

PMID- 16792613
TI  - Learning and performance of tracheal intubation by novice personnel: a comparison
      of the Airtraq and Macintosh laryngoscope.
AB  - Direct laryngoscopic tracheal intubation is taught to many healthcare
      professionals as it is a potentially lifesaving procedure. However, it is a
      difficult skill to acquire and maintain, and, of concern, the consequences of
      poorly performed intubation attempts are potentially serious. The Airtraq
      Laryngoscope is a novel intubation device which may possess advantages over
      conventional direct laryngoscopes for use by novice personnel. We conducted a
      prospective trial with 40 medical students who had no prior airway management
      experience. Following brief didactic instruction, each participant took turns in
      performing laryngoscopy and intubation using the Macintosh and Airtraq devices
      under direct supervision. Each student was allowed up to three attempts to
      intubate in three laryngoscopy scenarios using a Laerdal Intubation Trainer and
      one scenario in a Laerdal SimMan Manikin. They then performed tracheal intubation
      of the normal airway a second time to characterise the learning curve for each
      device. The Airtraq provided superior intubating conditions, resulting in greater
      success of intubation, particularly in the difficult laryngoscopy scenarios. In
      both easy and simulated difficult laryngoscopy scenarios, the Airtraq decreased
      the duration of intubation attempts, reduced the number of optimisation
      manoeuvres required, and reduced the potential for dental trauma. The Airtraq
      device showed a rapid learning curve and the students found it significantly
      easier to use. The Airtraq appears to be a superior device for novice personnel
      to acquire the skills of tracheal intubation.

PMID- 16792614
TI  - Comparison of the Berman Intubating Airway and the Williams Airway Intubator for
      fibreoptic orotracheal intubation in anaesthetised patients.
AB  - Sixty patients with no clinical indicators of a difficult airway were selected to
      undergo a fibreoptic assessment after induction of general anaesthesia using both
      the Berman Intubating Airway and the Williams Airway Intubator. The bronchoscopic
      view and ease of railroading a tracheal tube during fibreoptic orotracheal
      intubation were studied. The bronchoscopic views obtained by the Berman Airway
      and the Williams Airway were significantly different (p < 0.008, test of
      symmetry). The estimated odds ratio of obtaining an obstructed path was 3.06
      times higher for the Berman than the Williams Airway. However, if the glottis
      could be reached with the bronchoscope, there was no significant difference in
      the degree of ease of intubation between the two airways.

PMID- 16792615
TI  - Tracheal intubation using the ILMA, C-Trach or McCoy laryngoscope in patients
      with simulated cervical spine injury.
AB  - A study of 90 patients was undertaken to compare intubation success rates of
      using either ILMA, C-Trach or McCoy laryngoscope in patients with simulated
      cervical spine injury. Insertion and intubation success rates, time taken to
      achieve intubation, airway complications and haemodynamic parameters were
      recorded. Insertion of ILMA and C-Trach was successful at the first attempt in
      all patients. Intubation success rates were higher in the C-Trach (100%) and
      McCoy (100%) groups than in the ILMA (87%) group. Total intubation time was
      significantly longer in the ILMA (63 s, SD 36.5) group than in the C-Trach (41 s,
      SD 15.8) and McCoy (30 s, SD 7.4) groups (p < 0.05, p < 0.05, respectively).
      There were no significant differences in haemodynamic parameters among the groups
      at any time.

PMID- 16792616
TI  - A complication of transtracheal jet ventilation and use of the Aintree intubation
      catheter during airway resuscitation.
AB  - We report the management of a patient requiring surgical laryngoscopy with a view
      to laser resection of an epiglottic recurrence of laryngeal cancer. Previous
      attempts at tracheal intubation and awake nasal fibreoptic intubation had failed.
      During a previous anaesthetic the patient had been both 'impossible to intubate
      and to ventilate'. Neck scarring potentially complicated access for transtracheal
      jet ventilation. Nevertheless, a cricothyroid catheter was placed and surgery
      performed during low frequency 'volume' jet ventilation. Upper airway obstruction
      developed during the procedure, preventing exhalation, which led to raised
      intrathoracic pressure, cardiovascular collapse and barotrauma. The airway was re
      established by insertion of an LMA Proseal. Fibreoptic placement of an Aintree
      intubation catheter through this allowed re-oxygenation and exchange for a cuffed
      tracheal tube. Some hours after the procedure, re-intubation was necessary. This
      was achieved using the Aintree intubation catheter as an aid to nasal fibreoptic
      intubation and as a tube exchanger. Novel roles of the Aintree intubation
      catheter and LMA Proseal in this case are discussed. Complications of
      transtracheal jet ventilation as well as possible methods for avoiding them are
      also reviewed.

PMID- 16792617
TI  - Idiopathic non-histaminergic angio-oedema after routine extubation successfully
      treated with fresh frozen plasma.
AB  - Non-allergic angio-oedema is a potentially life-threatening condition typically
      seen in patients with hereditary or acquired angio-oedema caused by C1 inhibitor
      deficiency or an adverse drug reaction to angiotensin converting enzyme
      inhibitors. We report a case of sudden angio-oedema in a patient who developed
      severe swelling of the tongue and neck after routine extubation requiring
      resuscitative re-intubation. The oedema was refractory to conventional allergy
      treatment. Shortly thereafter, the patient was treated with fresh frozen plasma,
      and within a few hours his condition improved, allowing extubation. Familial
      history and exposure to potentially angio-oedema causative drugs were not
      evident. The serum complement status was normal, and no IgE sensitisation was
      detected. We therefore concluded that the patient was suffering from idiopathic
      non-histaminergic angio-oedema. To our knowledge, this is the first reported case
      of an acute, life-threatening attack of idiopathic non-histaminergic angio-oedema
      that was successfully treated with fresh frozen plasma.

PMID- 16792618
TI  - Transoesophageal echocardiography: a useful tool to diagnose entrapment of
      pulmonary artery catheter.
AB  - Placement of a pulmonary artery catheter during cardiac surgery is associated
      with various complications, one of which is entrapment. On the day following
      surgery unusual resistance was encountered while attempting to remove a pulmonary
      artery catheter from a patient who had undergone coronary artery bypass grafting.
      Entrapment of the catheter was confirmed by transoesophageal echocardiography,
      which demonstrated invagination of the free wall of the pulmonary trunk on gentle
      traction on the pulmonary artery catheter. Surgical exploration revealed that the
      catheter was transfixed by the suture used to close the pulmonary artery vent
      site. Surgical re-exploration and other potential complications related to
      catheter retrieval can be avoided if catheter entrapment is diagnosed intra
      operatively. We suggest that a high index of clinical suspicion along with the
      use of intra-operative transoesophageal echocardiography is considered in
      situations where catheter entrapment is a possibility.

PMID- 16792619
TI  - Keuskamp and the Amsterdam Infant Ventilator.
AB  - At the First International Symposium on the History of Modern Anaesthesia (1982),
      Professor Keuskamp mentioned that the introduction of breathing machines for lung
      ventilation during operations had taken over 'the tiresome handwork of
      ventilation'. This paper traces some aspects of Keuskamp's professional career
      and his role in the development of the Amsterdam Infant Ventilator. In 1974,
      Urban and Weitzner from the State University of New York reported that the
      ventilator was a reliable and effective constant-volume paediatric ventilator.
      Other clinicians from the United States and Europe echoed this satisfactory
      clinical evaluation. At present, this paediatric ventilator is still in use for
      the initial ventilation of small infants and for the mechanical ventilation of
      different animal species in a variety of experimental settings.

PMID- 16792620
TI  - The 'mesentery' dressing for epidural catheter fixation.

PMID- 16792621
TI  - Solo lists and the European Working Time Directive.

PMID- 16792623
TI  - Use of LMA ProSeal as a dedicated airway for fibreoptic-guided tracheal
      intubation.

PMID- 16792627
TI  - Pre-operative detection of valvular heart disease.

PMID- 16792624
TI  - The use of basophil activation to diagnose allergy to Gelofusine.

PMID- 16792628
TI  - Electric shock during cordotomy.

PMID- 16792629
TI  - Use of abciximab for aneurysm coiling.

PMID- 16792633
TI  - Kinking of disposable anaesthetic circuits.

PMID- 16792631
TI  - Intravenous ether for status asthmaticus.

PMID- 16792634
TI  - Spinal anaesthesia for spinal surgery.

PMID- 16792635
TI  - Smoking dragons.

PMID- 16792636
TI  - User damage to the tracheal tube used with the Intubating Laryngeal Mask Airway.

PMID- 16792637
TI  - Tracheal intubation in paediatrics: select tubes from the same manufacturer.

PMID- 16792638
TI  - Anaesthesia for stiff person syndrome: successful use of total intravenous
      anaesthesia.

PMID- 16792640
TI  - Botox injections and monitoring neuromuscular blockade.

PMID- 16792641
TI  - Treatment of idiopathic cutaneous hyperchromia of the orbital region (ICHOR) with
      intense pulsed light.
AB  - BACKGROUND: Idiopathic cutaneous hyperchromia of the orbital region (ICHOR) does
      not have a clear etiopathogenesis. Genetic factors, increased melanin, prominent
      vasculature, and eyelid skin slackness seem to be involved. OBJECTIVE: To
      evaluate individuals with ICHOR clinically and histologically, before and after
      treatment with high-energy pulsed light (HEPL), considering epidermal and dermal
      melanin, in order to evaluate HEPL efficacy in clearing away ICHOR, and 1 month
      and 1 year later to check whether improvement was maintained. METHODS: Twelve
      individuals with ICHOR underwent clinical and histological evaluation before and
      after HEPL application, with photographic comparison. They underwent one to four
      HEPL sessions on the lower eyelid at approximately 30-day intervals. Melanin
      quantification by area, before and after treatment was performed by digital image
      morphometry. RESULTS: Eyelid skin was significantly lightened (p = .24), and was
      maintained 1 year later with no ICHOR reincidence. All individuals (100%) showed
      postinflammatory hyperchromia (average 6-month duration), while 58.33% presented
      hypochromia (7-month duration). There was significantly decreased epidermal and
      dermal melanin after treatment. CONCLUSION: HEPL was shown to be useful in
      clearing up ICHOR. This was maintained after 1 year. Epidermal and dermal
      histopathology showed decreased melanin following treatment. Longer follow-up is
      needed to evaluate possible later recurrence of ICHOR.

PMID- 16792642
TI  - Condition known as "dark rings under the eyes" in the Japanese population is a
      kind of dermal melanocytosis which can be successfully treated by Q-switched ruby
      laser.
AB  - BACKGROUND: In general, dark rings under the eyes are believed to be a phenomenon
      caused mainly by physiological change because of their daily fluctuation.
      Medically speaking, the precise cause or pathogenesis of dark rings is unknown,
      and this condition has not been clearly defined. In our experience, the dark
      rings associated with conventional nevus of Ota can be successfully treated with
      Q-switched ruby laser (QSRL). OBJECTIVE: This study was conducted to clarify the
      nature of dark rings under the eyes and to determine the efficacy of QSRL.
      PATIENTS AND METHODS: Fifty-four patients who received a biopsy for pigment
      macules of the face were retrieved, and of that number 12 patients with bilateral
      homogeneous pigment macule on suborbital regions were selected for study of the
      dark rings. Of those patients, the histology and the efficacy of QSRL were
      evaluated retrospectively. RESULTS: Histologically, all 12 patients indicated
      dermal melanocytosis, which was confirmed by the Masson-Fontana silver stain and
      staining against S100. In five patients who received QSRL therapy two times or
      more, the clinical improvement of two patients was scored as good (40-69%), and
      two other patients as excellent (>70% clearance). CONCLUSIONS: We speculate that
      so-called dark rings under the eyes in the Japanese population is a kind of
      dermal melanocytosis which can be successfully treated by QSRL.

PMID- 16792643
TI  - Treatment of lymphangioma circumscriptum with combined radiofrequency current and
      900 nm diode laser.
AB  - BACKGROUND: Laser treatment of lymphangioma circumscriptum is a major challenge
      because of the persistent nature of the disease and the large variations in
      lesion size, depth, and anatomic location. OBJECTIVE: To determine the safety and
      effectiveness of electro-optical synergy, a new technology that combines a 900 nm
      diode laser with radiofrequency current, for the treatment of lymphangioma
      circumscriptum. METHODS: Six patients with Fitzpatrick skin types II to IV were
      treated for lymphangioma circumscriptum with 1 to 3 sessions of simultaneous
      radiofrequency energy (60-80 J/cm3) and optical diode laser energy (fluence 90
      100 J/cm2). Lesion clearance was evaluated by three specialists on the basis of
      digital photographs taken before the first treatment and 1 and 2 months after the
      last treatment. RESULTS: Results were rated as "excellent" in four patients and
      "good" in two patients. Transient swelling, erythema, and pain were present in
      all patients, and ulcers and scarring in two patients. CONCLUSION: The
      combination of laser light and radiofrequency energy is effective and relatively
      safe for the treatment of lymphangioma circumscriptum. It provides additional
      heating of the blood vesicles without increasing the laser intensity and allows
      the clinician to treat the clear lymphatic component, which lacks a specific
      optical chromophore. Side effects are tolerable.

PMID- 16792644
TI  - Split-face comparison of photodynamic therapy with 5-aminolevulinic acid and
      intense pulsed light versus intense pulsed light alone for photodamage.
AB  - BACKGROUND: Photodynamic therapy (PDT) with a 5-aminolevulinic acid (ALA)
      photosensitizing agent and a variety of lasers and light sources has been shown
      to enhance the treatment of photodamaged skin and its associated actinic
      keratoses (AKs). The efficacy of short-contact, full-face ALA by PDT in
      photorejuvenation has also been demonstrated. OBJECTIVE: To evaluate short
      contact (30 to 60 min) ALA-PDT with intense pulsed light (IPL) activation by
      comparing ALA-PDT-IPL with IPL alone. METHODS Sixteen patients were enrolled in a
      split-face study. One side of each patient's face received ALA-PDT-IPL and the
      other side received IPL alone. Three treatments were given at 1-month intervals,
      and follow-up visits occurred at 1 and 3 months after the final treatment.
      RESULTS: Thirteen patients completed the trial. Three months after the final
      treatment, improvement was greater in the ALA-PDT-IPL side than in IPL-alone side
      for all facets of photodamage-crow's feet appearance (55 vs 29.5%), tactile skin
      roughness (55 vs 29.5%), mottled hyperpigmentation (60.3 vs 37.2%), and
      telangectasias (84.6 vs 53.8%). The clearance rate of AK lesions was also higher
      (78 vs 53.6%). CONCLUSION: Short-contact ALA-PDT-IPL brings about greater
      improvement in photodamaged skin and greater clearance of AK lesions than IPL
      alone, further confirming the usefulness of ALA-PDT in photorejuvenation.

PMID- 16792645
TI  - Use of a biopolymer polyalkylimide filler for facial lipodystrophy in HIV
      positive patients undergoing treatment with antiretroviral drugs.
AB  - OBJECTIVES: To evaluate the efficacy, overall esthetic effect, and safety of a
      new permanent, polyalkylimide dermal filler in HIV-infected patients with severe
      facial lipodystrophy. METHODS: Eleven subjects with severe facial lipodystrophy
      secondary to HIV infection were injected bilaterally with 15 and 30 cm3 of a
      polyalkylimide gel into the buccal, malar, and temporal areas of the face in an
      attempt to restore their facial contour. The youngest treated subject was 31
      years of age and the oldest 73 years of age. RESULTS: All 11 subjects received an
      immediately acceptable therapeutic esthetic effect. Injections were generally
      well tolerated, with only three adverse events (swelling and bruising) recorded.
      Subjects, assessed at 3 and 18 months after treatment, continued to show
      improvement. CONCLUSIONS: The immediate benefits of a polyalkylimide gel in the
      correction and restoration of facial contour in subjects having severe HIV
      related facial lipodystrophy were demonstrated. This improvement was still noted
      at 18 months. The efficacy, ease of injection, and safety profile of
      polyalkylimide gel make this filling material a potentially attractive treatment
      for lipodystrophy. These data must be tempered with the need for significant
      further safety studies to determine whether this long-term filler has a safety
      profile consistent with other currently popular fillers.

PMID- 16792646
TI  - Microdermabrasion: Reappraisal and brief review of literature.
AB  - BACKGROUND: Microdermabrasion (MDA) is a recently introduced noninvasive,
      nonsurgical, office-based esthetic procedure for revitalizing and rejuvenating
      the skin. It is a closed-loop vacuum-assisted abrasive procedure, which uses the
      physical action of inert crystals to exfoliate the skin. OBJECTIVE: The aim was
      to evaluate the procedure of MDA in postacne scarring, melasma, and facial
      rejuvenation, and review the relevant literature. METHODS: Ten patients each of
      postacne scarring, melasma, and facial rejuvenation were treated by a series of
      weekly MDA sittings alone or in conjunction with a topical retinoid. The results
      were assessed by patient questionnaire and an objective assessment by two
      independent observers. The literature was reviewed to find indications and
      efficacy of MDA. RESULTS: All the patients of postacne scarring, melasma, and
      facial rejuvenation reported a mild but definite improvement, which increased
      when MDA was performed in conjunction with a topical retinoid. Most of the
      literature based on subjective and patient-dependent assessment parameters points
      toward a marginal improvement in the skin appearance following repeated
      procedures. CONCLUSION: Reappraisal of this potentially useful procedure points
      toward a need for well-designed clinical trials and studies with a long follow-up
      based on objective assessment parameters.

PMID- 16792647
TI  - Survival rate according to grafted density of Korean one-hair follicular units
      with a hair transplant implanter: Experience with four patients.
AB  - BACKGROUND: The survival rate of grafted hairs in hair transplantation has been
      frequently discussed by many hair-transplant surgeons. Several factors, including
      skill of doctors and assistants and the amount of perifollicular connective
      tissue, are suggested to have predictive values in foretelling the eventual
      quantity of hair growth. OBJECTIVE: The purpose of this study is to determine
      survival rate according to density of Korean one-hair follicular units grafted
      with a KNU implanter. METHODS: We designed four templates of 1 cm2 made by
      tattooing two templates on each side of empty frontoparietal recesses in four
      Korean patients with male pattern alopecia (beyond Norwood-Hamilton-Type IIIa).
      One-hair follicular units were prepared from occiput and we grafted 20, 30, 40,
      and 50 one-hair follicular units using a KNU implanter on each template,
      respectively, and counted the number of surviving hairs after 10 months. RESULTS:
      The survival rate of 20 and 30 grafts per template was higher than that of 40 and
      50 grafts. CONCLUSION: We think that 30 one-hair follicular units grafted with a
      KNU implanter is the proper density for better survival in Korean hair
      transplantation, and repeated sessions will be necessary for a better final
      result. However, we need further evaluation with a larger number of participants
      to overcome the small sample size and limitation of one-hair follicular unit
      grafts. The authors have indicated no significant interest with commercial
      supporters.

PMID- 16792648
TI  - Prospective study of wound infections in dermatologic surgery in the absence of
      prophylactic antibiotics.
AB  - OBJECTIVE: The study aimed to identify wound sites/procedures where infection
      incidence was over 5%, such that these circumstances may warrant wound infection
      antibiotic prophylaxis. METHOD: We undertook a 3-year prospective study of 5,091
      lesions (predominantly nonmelanoma skin cancer) treated on 2,424 patients from
      July 2002 to June 2005. No patient was given prophylactic antibiotics, and no
      patient ceased warfarin or aspirin. RESULTS: Overall infection incidence was
      1.47%. Individual procedures had the following infection incidence: curettage
      0.73% (3/412); skin flap repairs 2.94% (47/1601); simple excision and closure
      0.54% (16/2974); skin grafts 8.70% (6/69); and wedge excision 8.57% (3/35).
      Analysis of regions of the body demonstrated that surgery below the knee (n =
      448) had an infection incidence of 6.92% (31/448) (p < .0001). Subanalysis
      demonstrated that all regions below the knee were at high infection risk.
      Elsewhere, groin excisional surgery had an infection incidence of 10% (1/10) (p =
      .027). No other body site demonstrated an infection incidence beyond 5% of
      statistical significance. Procedures on the face demonstrated an infection
      incidence of 0.81% (18/2,209). Diabetic patients, those on warfarin and/or
      aspirin, and smokers showed no difference in infection incidence. CONCLUSION:
      Based on a prediction of infection incidence over 5%, the following cutaneous
      oncologic procedures warrant consideration of oral antibiotic wound infection
      prophylaxis: all procedures below the knee, wedge excisions of lip and ear, all
      skin grafts, and lesions in the groin. Other than under these circumstances,
      surgery to the nose, ear, fingers, lips, skin flap surgery, and surgery on
      diabetics, smokers, and those on anticoagulants have previously been considered
      for wound infection prophylaxis but do not warrant such intervention based on our
      data. The authors have indicated no significant interest with commercial
      supporters.

PMID- 16792649
TI  - How low should you go: novel device for nail trephination.
AB  - BACKGROUND: The most commonly used treatment for subungual hematomas is nail
      trephination, a technique that is not standardized and that poorly controls for
      trephination depth. OBJECTIVE: The objective was to test the safety and tolerance
      of a new device for nail trephination that uses innovative "mesoscission" or
      microcutting technology to create holes of specific depths in the nail plate
      without penetrating the nail bed. MATERIALS AND METHODS: Fourteen adult subjects
      with healthy toenails had five holes drilled in a random single-blind fashion at
      different test settings into their right great toenail with this device and were
      assessed for pain and pressure tolerance as well as perioperative and
      postoperative complications. RESULTS: Nail trephination with this device in this
      small pilot study was controlled and well tolerated. LIMITATIONS: The study
      population was small (n = 14) and the follow-up evaluation relied on patient self
      report, which is not always reliable. The follow-up period was only 1 week and
      did not allow for evaluation of permanent nail plate deformity. CONCLUSION:
      Mesoscission may be a controlled and practical alternative to traditional nail
      trephining methods.

PMID- 16792650
TI  - Integrating digital image management software for improved patient care and
      optimal practice management.
AB  - BACKGROUND: Photographic images provide vital documentation of preoperative,
      intraoperative, and postoperative results in the clinical dermatologic surgery
      practice and can document histologic findings from skin biopsies, thereby
      enhancing patient care. Images may be printed as part of text documents,
      transmitted via electronic mail, or included in electronic medical records.
      OBJECTIVES: To describe existing computer software that integrates digital
      photography and the medical record to improve patient care and practice
      management. CONCLUSIONS: A variety of computer applications are available to
      optimize the use of digital images in the dermatologic practice.

PMID- 16792653
TI  - Repair of large defects in the forehead using a median forehead rotation flap and
      advancement lateral U-shaped flap.
AB  - BACKGROUND: The forehead is a large and highly expressive and dynamic cosmetic
      unit. Most forehead defects that cannot be closed primarily are reconstructed
      with laterally based advancement flaps. OBJECTIVE: A combination of median
      forehead rotation flap and advancement lateral U-shaped flap for repair of medium
      to-large-size defects in paramedian and lateral forehead is described. METHODS:
      Technically, the design of median forehead rotation flap based on supratrochlear
      vessels used here is similar to the median forehead transposition flap used to
      reconstruct large defects of the nasal dorsum. The length and the movement of the
      flap are much smaller in this case. Approximately 2/3 of the closure of the
      defect is achieved by displacing the median forehead flap while the remaining 1/3
      corresponds to the advancement of the lateral U-shaped flap. RESULTS: The flaps
      are simple to perform, have minimal complications, and have good cosmetic
      results. A representative case is presented with photographs. CONCLUSION: For
      selected medium- to large-size horizontal defects in the paramedian and the
      lateral forehead, the combination of a median forehead rotation flap and an
      advancement lateral U-shaped flap offers a simple, visually pleasing repair that
      preserves the forehead architecture.

PMID- 16792654
TI  - Dermoscopy in Gorlin-Goltz syndrome.
AB  - BACKGROUND: Gorlin-Goltz syndrome (GGS) is an autosomal dominant disorder mainly
      characterized by the presence of multiple basal cell carcinomas (BCC),
      odontogenic keratocysts of the jaw, and volar pits. This syndrome is associated
      with a wide spectrum of developmental anomalies and neoplasms. OBJECTIVE: To
      describe dermoscopic characteristics of cutaneous GGS lesions performing
      histopathologic correlation. MATERIALS AND METHODS: Cutaneous lesions and tumors
      from five patients affected by GGS were included. Clinical and dermoscopy images
      were obtained and excision with ulterior histopathology performed in suspicious
      tumors. RESULTS: With dermoscopy, BCCs can be detected in early stages by the
      presence of blue-gray globules in lesions less than 3 mm in diameter. In larger
      lesions, arborizing telangiectasia may also be present. Acral pits that are often
      overlooked during physical examination have a characteristic dermoscopy with red
      globules that are mainly distributed in parallel lines inside flesh-colored,
      irregular-shaped, and slightly depressed lesions. Dermoscopy improves the
      visualization of these pits. CONCLUSION: Dermoscopy can help in the diagnosis of
      the GGS as well as in the management of affected patients.

PMID- 16792655
TI  - Dermoscopic features of cutaneous lymphangioma circumscriptum.
AB  - BACKGROUND: Cutaneous lymphangioma circumscriptum (CLC) is clinically
      characterized by clusters of translucent vesicles that may be filled by blood.
      OBJECTIVE: To evaluate the dermoscopic features of CLC. MATERIALS AND METHODS:
      Dermoscopic examination was performed in two cases presenting with discrete
      translucent and blood-tinged lesions. RESULTS: Lesions filled with clear fluid
      were dermoscopically characterized by light brown lacunas surrounded by paler
      septa. Lesions tinged with blood were associated with different dermoscopic
      features depending on the amount of blood content: focal reddish areas inside the
      lagoons, pink diffuse coloration, reddish to violaceous lacunar structures.
      CONCLUSIONS: On dermoscopy, CLC was characterized by a lacunar pattern. Lesions
      with a marked hematic content show dermoscopic findings indistinguishable from
      those of hemangioma.

PMID- 16792656
TI  - Advancement flap in the reconstruction of lateral nasal sidewall defect.

PMID- 16792657
TI  - Human papillomavirus isolated from transplant-associated porokeratoses of mibelli
      responsive to topical 5% imiquimod cream.

PMID- 16792658
TI  - Perineural invasion of a Ferguson-Smith-type keratoacanthoma.

PMID- 16792659
TI  - Squamous cell carcinoma arising within a facial port-wine stain treated by mohs
      micrographic surgical excision.

PMID- 16792660
TI  - Selective spread of a malignant melanoma into a graft after ten years: A case of
      delayed Koebner phenomenon.

PMID- 16792661
TI  - Inverse halo nevus.

PMID- 16792662
TI  - Cryoanalgesia with dichlorotetrafluoroethane spray versus ice packs in patients
      treated with botulinum toxin-a for palmar hyperhidrosis: Self-controlled study.

PMID- 16792663
TI  - Light-assisted hair removal in patients undergoing isotretinoin therapy.

PMID- 16792664
TI  - Conservative management of flap necrosis after expanding hematomas for face
      lifting surgery.

PMID- 16792666
TI  - The contribution of Bruce Glick to the definition of the role played by the bursa
      of Fabricius in the development of the B cell lineage.
AB  - In 1956, Bruce Glick and Timothy Chang reported that the bursa of Fabricius plays
      an important role in antibody production. Their demonstration that antibody
      responses are suppressed in the majority of bursectomized chickens became the
      cornerstone of modern immunology. Bursa research increased considerably during
      the 1960s and early 1970s.

PMID- 16792667
TI  - High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates.
AB  - Mannose-binding lectin (MBL) is a component of innate immunity and thus
      particularly important in neonates in whom adaptive immunity is not yet
      completely developed. Promoter polymorphisms and structural exon-1 mutations in
      the MBL2 gene cause reduced or deficient MBL plasma concentrations. The aim of
      our study was to determine the prevalence of MBL deficiency in neonates admitted
      to the neonatal intensive care unit (NICU). Eighty-five NICU patients (69
      premature) were included in the study. We measured MBL concentrations in
      umbilical cord and neonatal blood within 24 h after birth by ELISA technique.
      MBL2 genotypes (n = 67) were determined by Taqman analysis. MBL concentrations
      were measured longitudinally during three weeks in 26 premature neonates. The
      association between pre- and intra-partum clinical data and MBL concentrations
      was investigated. At birth, 29 (42%) premature and six (38%) term neonates had
      MBL plasma concentrations < or = 0.7 microg/ml which was regarded as deficient.
      Twenty-one (38%) premature and four (36%) term neonates had variant MBL2
      haplotypes, corresponding to exon-1 mutations and the LXPA haplotype. MBL
      concentrations increased over time in neonates with wild-type MBL2 haplotypes,
      but not in neonates with variant haplotypes. Low MBL plasma concentrations were
      related to lower gestational age and variant MBL2 haplotypes. Umbilical cord and
      neonatal MBL plasma concentrations appeared to be similar. In conclusion, almost
      half of our NICU patients, especially the premature ones, were MBL-deficient at
      birth. These infants may be at increased risk of neonatal infections. MBL
      concentration can reliably be measured in umbilical cord blood and it is
      positively correlated with gestational and postnatal age.

PMID- 16792669
TI  - Cross-reaction of anti-DNA autoantibodies with membrane proteins of human
      glomerular mesangial cells in sera from patients with lupus nephritis.
AB  - Anti-DNA autoantibodies were thought to play a major role in the pathogenesis of
      lupus nephritis (LN). A recent study revealed that affinity-purified anti-DNA
      antibodies had a cross-reaction with human glomerular mesangial cells (HMC).
      However, whether the cross-reaction was antigen-antibody-mediated was unclear.
      The aim of the current study was to investigate the binding of anti-DNA
      antibodies to HMC membrane proteins and to characterize the target antigens.
      Affinity-purified IgG anti-DNA antibodies were purified by DNA-cellulose
      chromatography in sera from nine patients with biopsy-proven active lupus
      nephritis. In vitro cultured primary HMCs were disrupted by sonication and HMC
      membranes were obtained by differential centrifugation. The membranes of human
      umbilical vein endothelial cells (HUVEC), human proximal renal tubular epithelial
      cell line (HK2) and peripheral mononuclear cells (PMC) were obtained as controls.
      Binding of anti-DNA antibodies to the membrane proteins was investigated by
      Western blot analysis using soluble membrane proteins as antigens. Both HMC
      membrane and affinity-purified anti-DNA antibodies were treated with DNase I to
      exclude DNA bridging. All nine affinity-purified anti-DNA antibodies could blot
      the HMC membrane proteins, and there were at least three bands at 74 kDa, 63 kDa
      and 42 kDa that could be blotted. Among the nine IgG preparations, all nine
      (100%) could blot the 74 kDa band; eight (88.9%) could recognize 63 kDa and 42
      kDa protein bands separately. After DNase treatment, the same bands could still
      be blotted by most affinity-purified anti-DNA antibodies. Affinity-purified anti
      DNA antibodies could also blot similar bands on membrane proteins of other cells,
      but some bands were different. In conclusion, anti-DNA autoantibodies could cross
      react directly with cell membrane proteins of human glomerular mesangial cells
      and might play an important role in the pathogenetic mechanism in lupus
      nephritis.

PMID- 16792668
TI  - Mucosal lymphocyte subsets and HLA-DR antigen expression in paediatric
      Helicobacter pylori-associated gastritis.
AB  - Paediatric studies may provide important insights into the immunopathology of
      Helicobacter pylori-associated gastritis, as mucosal changes reflect different
      stages of the immunoinflammatory response. We characterized, by quantitative
      immunohistochemistry, gastric mucosal lymphocyte phenotype and HLA-DR antigen
      expression and evaluated correlation with histopathology, in H. pylori-infected
      (Hp+ve) and uninfected children (Hp-ve). In the infected group, lamina propria
      CD3+ and IgA plasmocyte cell numbers were significantly higher and a trend for
      predominance of CD8+ over CD4+ was observed both in epithelium and lamina
      propria. A correlation of inflammation score with lamina propria CD3+ and CD4+
      cell numbers and of CD45RO+ T lymphocytes with density of colonization was
      observed. The proportion of epithelial cells expressing HLA-DR antigen was
      significantly higher in the Hp+ve group and furthermore, glandular HLA-DR
      expression correlated with lamina propria CD3+ cell numbers, emphasizing the
      potential role of epithelial cells as antigen-presenting cells at this stage of
      infection.

PMID- 16792670
TI  - Comparison of reactivity and epitope recognition between sera from American and
      Italian patients with oral pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) (also known as cicatricial pemphigoid) is a rare
      autoimmune mucocutaneous blistering disease that affects mucous membranes derived
      from stratified squamous epithelium and the skin. A subset of MMP affects only
      the oral cavity and is referred to as the oral pemphigoid (OP). MMP and OP are
      characterized by subepithelial vesicles on histology and in vivo deposition of
      immunoglobulins and complement at the basement membrane zone (BMZ) on
      immunopathology. Previous studies have shown that sera of patients with MMP bind
      to human integrin beta4, while sera of patients with oral pemphigoid bind to the
      integrin alpha6 component of the heterodimer. The prognosis in MMP is grave but
      excellent in OP. In this study we compare the binding of sera from patients with
      OP from Boston, MA, USA to Naples, Italy, and attempt to identify an epitope to
      which the anti-integrin alpha6 human autoantibody binds. Our results indicate
      that the sera from Boston and Naples are identical in their reactivity. They
      recognize a fragment I (AA 23-462) and its subfragment IB (AA 217-462) only, in
      the human integrin alpha6 molecule. Blocking studies, immunoprecipitation and
      immunoabsorbtion studies confirm the presence of this single 245 AA region.
      Antibodies to subfragment IB cause BMZ separation in organ culture using normal
      human oral mucosa as substrate. This preliminary study indicates that patients on
      both continents may have similar reactivity and suggests that an intercontinental
      study group could be established to advance our understanding of the pathogenesis
      of OP and the biology of anti-alpha6 integrin autoantibodies.

PMID- 16792672
TI  - Soluble CD26/CD30 levels in visceral leishmaniasis: markers of disease activity.
AB  - Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis
      (VL). If untreated the disease could be fatal; however, in some cases the
      infection can run a subclinical course. In subclinical infections a Th1-response
      predominates, while Th2-responses and/or probably Treg cells are related to
      unfavourable outcome of the disease in active VL. In the present study we
      determined the levels of soluble (s) CD26 and CD30 co-stimulatory molecules in
      sera from patients with active VL, asymptomatic individuals and healthy
      volunteers. Results showed a significant difference in both sCD26 and sCD30
      between infected cases and normal individuals (P < or = 0.001). However, there
      was no significant difference in sCD26 levels between asymptomatic cases and
      patients, although the difference was not significant. sCD30 levels were
      significantly higher in VL patients than asymptomatic cases (P < or = 0.001).
      These findings suggest a possible association between sCD26 and sCD30 levels and
      the clinical manifestation of L. infantum infection.

PMID- 16792671
TI  - Activation-associated phenotype of CD3 T cells in acute graft-versus-host
      disease.
AB  - During the effector phase of graft-versus-host disease (GvHD) response, donor T
      cells play an essential role and they are believed to change the expression of
      activation and co-stimulatory markers associated with functional alloreactivity.
      We analysed the expression of CD25, CD69, HLA-DR, CD154 and CD134 on CD4+ and
      CD8+ T cells by flow cytometry during acute GvHD (aGvHD) in 24 patients receiving
      human leucocyte antigen (HLA)-identical stem cell transplants. Expression of
      these molecules in nine patients with stages I-IV aGvHD was compared with 15
      patients without aGvHD (n = 15). Serial analysis showed that peripheral blood of
      aGvHD patients presented a significant increase of CD4+ CD25+ cells (P < 0.03),
      CD4+ CD69+ (P < 0.04) and CD4+ CD134+ cells (P < 0.01). Additionally, there was a
      significant increase in CD8+ cells expressing CD134 (P = 0.007) and CD154 (P =
      0.02). After resolution of aGvHD, the increased expression of these molecules
      returned to values comparable to patients without aGvHD. Only two of the 15
      patients without clinical signs of aGvHD presented activated T cells that could
      not be attributed to development of aGvHD. In summary, our data show that
      multiple activation molecules are preferentially up-regulated on CD4+ and CD8+ T
      cells from patients with aGvHD. These patients had a significant increase in the
      expression of the co-stimulatory molecules CD134 and CD154.

PMID- 16792673
TI  - The association of CTLA-4 and HLA class II autoimmune risk genotype with
      regulatory T cell marker expression in 5-year-old children.
AB  - Regulatory T cells (Treg) are involved in the maintenance of peripheral tolerance
      by suppression of autoreactive lymphocytes that have avoided thymic depletion.
      The defective function of Treg cells has recently attracted attention in
      autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis and
      multiple sclerosis. Susceptibility to these diseases is associated with specific
      human leucocyte antigen (HLA) class II and cytotoxic T lymphocyte-associated
      antigen 4 (CTLA-4) gene polymorphisms. This study aimed to investigate the
      relationship between HLA class II and CTLA +49 A/G polymorphisms associated with
      susceptibility to T1D and the number and characteristics of Treg cells in
      children. Samples from 47 5-year-old children who participated in the All Babies
      in South-east Sweden (ABIS) follow-up study were grouped according to the
      presence of the T1D risk-associated HLA genotype (DQA1*0501-DQB1*0201, DQA1*0301
      DQB1*0302) or neutral HLA genotypes. Lower percentages of CD4+ T cells (P = 0.03)
      and CD4+ CD25high cells (P = 0.06) expressing intracellular CTLA-4 were detected
      in samples from children with CTLA-4 +49GG compared to children with the +49AA
      genotype. Similarly, lower percentages of CD4+ (P = 0.002) and CD4+ CD25high (P =
      0.002) cells expressing CTLA-4 were observed in children positive for HLA
      DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302 (P = 0.04 for CD4+ and P = 0.02 for
      CD4+ CD25high) risk haplotypes when compared to children without these alleles.
      The percentage of CD25high cells among CD4+ cells was correlated inversely with
      CTLA-4 mRNA expression in PBMC (r = -0.56, P = 0.03). Decreased levels of CTLA-4
      in CD4+ and CD4+ CD25high cells in individuals with CTLA-4 and HLA class II
      alleles associated with T1D may contribute to the initiation and/or progression
      of autoimmune response.

PMID- 16792674
TI  - Antibodies targeting the calcium binding skeletal muscle protein calsequestrin
      are specific markers of ophthalmopathy and sensitive indicators of ocular
      myopathy in patients with Graves' disease.
AB  - We have identified several eye muscle antigens and studied the significance of
      the corresponding serum autoantibodies in patients with Graves' disease. Of these
      antigens, only calsequestrin is expressed more in eye muscle than other skeletal
      muscles, which could explain at least partly the specific involvement of eye
      muscle in patients with Graves' disease. Earlier, we found a modest relationship
      between anti-calsequestrin antibodies and ophthalmopathy, but in that study we
      used calsequestrin prepared from rabbit heart muscle and measured antibodies by
      immunoblotting. We have reinvestigated the prevalences of anti-calsequestrin
      antibodies in larger groups of well-characterized patients with thyroid
      autoimmunity with and without ophthalmopathy and control patients and healthy
      subjects, using standard enzyme-linked immunosorbent assay incorporating highly
      purified rabbit skeletal muscle calsequestrin, which has a 97% homology with
      human calsequestrin, as antigen. Anti-calsequestrin antibodies were detected in
      78% of patients with active congestive ophthalmopathy, in 92% of those with
      active inflammation and eye muscle involvement, but in only 22% of patients with
      chronic, 'burnt out' disease. Tests were also positive in 5% of patients with
      Graves' hyperthyroidism without evident ophthalmopathy (two patients) and one
      patient with 'watery eyes' but no other clear signs of congestive ophthalmopathy
      and IgA nephropathy and no known thyroid disease, but in no patient with
      Hashimoto's thyroiditis, toxic nodular goitre, non-toxic multi-nodular goitre or
      diabetes, or age- and sex-matched healthy subjects. In serial studies of all 11
      patients with Graves' hyperthyroidism who had active ophthalmopathy at the time
      of the first clinic visit, or developed eye signs during the first 6 months, and
      positive anti-calsequestrin antibodies in at least one sample, anti-calsequestrin
      antibodies correlated with the onset of ocular myopathy in six patients.
      Antibodies targeting calsequestrin appear to be specific markers for
      ophthalmopathy and sensitive indicators of the ocular myopathy subtype of
      ophthalmopathy in patients with thyroid autoimmunity. However, these results must
      be considered preliminary until a large prospective study of patients with newly
      diagnosed Graves' hyperthyroidism, in which serum levels of calsequestrin
      antibodies are correlated with clinical changes and orbital eye muscle and
      connective tissue/fat volumes, has been carried out.

PMID- 16792675
TI  - Increased neutrophil membrane expression and plasma level of proteinase 3 in
      systemic vasculitis are not a consequence of the - 564 A/G promotor polymorphism.
AB  - Several findings link proteinase 3 (PR3) to small vessel vasculitis. Besides
      being a major target of anti-neutrophil cytoplasm antibodies (ANCA), previous
      findings have shown increased circulating levels of PR3 in vasculitis patients,
      increased levels of neutrophil membrane-PR3 (mPR3) expression and a skewed
      distribution of the - 564 A/G polymorphism in the promotor region of the PR3
      gene. In this study we elucidate how these three findings relate to each other.
      The plasma concentration of PR3 was measured by enzyme-linked immunosorbent assay
      (ELISA), mPR3 expression by fluorescence activated cell sorter (FACS) and the
      gene polymorphism by real-time polymerase chain reaction (PCR). We compared
      results from 63 patients with ANCA-associated systemic vasculitis (AASV) with 107
      healthy blood donors. In accordance with previous reports, AASV patients had
      increased plasma concentrations of PR3 compared to healthy controls (mean 224
      microg/l versus 155 microg/l, P < 0.0001). They also showed an increased number
      of mPR3-positive neutrophils (60%versus 42%, P < 0.001). However, contrary to a
      previous report, we found no skewed distribution of the polymorphism in PR3 gene.
      There was a weak correlation between mPR3 mean fluorescence intensity (MFI) and
      plasma PR3 among healthy controls and myeloperoxidase-ANCA (MPO-ANCA)-positive
      patients (r = 0.24, P = 0.015 and r = 0.52, P = 0.011, respectively). In
      conclusion, increased plasma PR3 and high expression of mPR3 are associated with
      small vessel vasculitis, but neither of them is a consequence of the - 564 A/G
      polymorphism of the PR3 gene promotor.

PMID- 16792676
TI  - Suspects in the tale of lupus-associated thrombocytopenia.
AB  - Immunologically mediated thrombocytopenia is a frequent clinical manifestation in
      patients with systemic lupus erythematosus (SLE). Autoantibodies targeting
      platelet membrane glucoproteins have a central role in peripheral platelet
      destruction. Autoantibodies against thrombopoietin are also present in about one
      third of patients, but their pathogenetic role is obscure. Thirty-eight serum
      samples from SLE patients were tested for anti-platelet antibodies, anti
      thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow
      histology was also assessed. Thirty-nine per cent of sera displayed anti
      thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti
      thrombopoietin antibodies were associated with lower thrombopoietin
      concentrations, and lower mean platelet values in long-term follow-up. Anti
      platelet antibodies were present in about 40% of thrombocytopenic and non
      thrombocytopenic individuals but were absent in patients who had recovered from
      thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were
      absent in control sera from patients with rheumatoid arthritis and primary
      Sjogren's syndrome. Decreased bone marrow cellularity, normal or low number of
      hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent
      findings in thrombocytopenic SLE patients, suggesting a defect in
      megakaryopoiesis. These findings were not evident in specimens from patients with
      idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal
      cellularity and absence of stromal alterations. In conclusion, peripheral
      destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower
      effective circulating thrombopoetin and impaired compensatory response due to
      bone marrow damage interact in SLE and thrombocytopenia ensues.

PMID- 16792677
TI  - Are increased frequency of macrophage-like and natural killer (NK) cells,
      together with high levels of NKT and CD4+CD25high T cells balancing activated
      CD8+ T cells, the key to control Chagas' disease morbidity?
AB  - The immunological response during early human Trypanosoma cruzi infection is not
      completely understood, despite its role in driving the development of distinct
      clinical manifestations of chronic infection. Herein we report the results of a
      descriptive flow cytometric immunophenotyping investigation of major and minor
      peripheral blood leucocyte subpopulations in T. cruzi-infected children,
      characterizing the early stages of the indeterminate clinical form of Chagas'
      disease. Our results indicated significant alterations by comparison with
      uninfected children, including increased values of pre-natural killer (NK)-cells
      (CD3- CD16+ CD56-), and higher values of proinflammatory monocytes (CD14+ CD16+
      HLA-DR++). The higher values of activated B lymphocytes (CD19+ CD23+) contrasted
      with impaired T cell activation, indicated by lower values of CD4+ CD38+ and CD4+
      HLA-DR+ lymphocytes, a lower frequency of CD8+ CD38+ and CD8+ HLA-DR+ cells; a
      decreased frequency of CD4+ CD25HIGH regulatory T cells was also observed. These
      findings reinforce the hypothesis that simultaneous activation of innate and
      adaptive immunity mechanisms in addition to suppression of adaptive cellular
      immune response occur during early events of Chagas' disease. Comparative cross
      sectional analysis of these immunophenotypes with those exhibited by patients
      with late chronic indeterminate and cardiac forms of disease suggested that a
      shift toward high values of macrophage-like cells extended to basal levels of
      proinflammatory monocytes as well as high values of mature NK cells, NKT and
      regulatory T cells, may account for limited tissue damage during chronic
      infection favouring the establishment/maintenance of a lifelong indeterminate
      clinical form of the disease. On the other hand, development of an adaptive cell
      mediated inflammatory immunoprofile characterized by high levels of activated
      CD8+ cells and basal levels of mature NK cells, NKT and CD4+ CD25HIGH cells might
      lead to late chronic pathologies associated with chagasic heart disease.

PMID- 16792679
TI  - Fumaric acid esters are effective in chronic experimental autoimmune
      encephalomyelitis and suppress macrophage infiltration.
AB  - Fumaric acid esters (FAE) have proven their therapeutic efficacy in psoriasis, a
      Th1 mediated skin disease. More recently, preliminary data have suggested an
      activity in multiple sclerosis (MS) as well. To investigate further possible
      mechanisms of action of these compounds in inflammatory diseases, we studied the
      FAE methyl hydrogen fumarate (MHF) and dimethyl fumarate (DMF) in chronic
      experimental autoimmune encephalomyelitis (EAE) induced by immunization of
      C57BL/6 mice with MOG peptide aa 35-55. Preventive treatment with these FAE was
      delivered twice a day by oral gavage. Both esters had a significant therapeutic
      effect on the disease course and histology showed a strongly reduced macrophage
      inflammation in the spinal cord. Multiparameter cytokine analysis from blood
      detected an increase of IL-10 in the treated animals. We conclude that the
      underlying biological activity of FAE in EAE is complex and, to elucidate the
      molecular mechanisms, further investigation is needed.

PMID- 16792678
TI  - Transgenic mice aberrantly expressing pyruvate dehydrogenase complex E2 component
      on biliary epithelial cells do not show primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune disorder that specifically
      destroys biliary epithelial cells (BECs). In patients with PBC, the
      immunodominant pyruvate dehydrogenase complex E2 component (PDC-E2), identified
      as an antigen for disease-specific anti-mitochondrial antibody, is expressed
      aberrantly in the BEC cytoplasm. The present study focused on the
      pathophysiological role of aberrant PDC-E2 in the development of PBC. The BEC
      specific cytokeratin-19 promoter and PDC-E2 gene were cloned from a mouse cDNA
      library. The constructed transgene was microinjected into fertilized eggs of
      mice, and the offspring were identified by Southern blotting and reverse
      transcriptase-polymerase chain reaction. The protein expression was confirmed by
      immunoprecipitation, immunoblotting and immunohistochemical staining. Five
      founder lines were identified as carrying the PDC-E2 gene, and one of these lines
      expressed PDC-E2 mRNA. The protein expression of exogenous PDC-E2 was detected in
      the liver. The transgenic mouse line showed diffuse expression of PDC-E2 in the
      BEC cytoplasm. Biochemical, serological and histological features of PBC were not
      detected. We established transgenic mice that constitutively express PDC-E2. The
      results indicated that aberrant PDC-E2 expression in the cytoplasm of BECs is not
      sufficient for the initiation of autoimmunity. Additional factors may be required
      to establish a model of PBC.

PMID- 16792680
TI  - IgM-enriched human intravenous immunoglobulin suppresses T lymphocyte functions
      in vitro and delays the activation of T lymphocytes in hu-SCID mice.
AB  - Previous studies of an experimental human immunoglobulin preparation for
      intravenous use, containing normal pooled IgM (IVIgM), have shown its beneficial
      therapeutic effect in experimental autoimmune diseases. The mechanisms of its
      immunomodulatory activity remain however, poorly understood. In the experiments
      reported here, IVIgM inhibited the proliferation of various autonomously growing
      human lymphoid cell lines in vitro, as well as of MLR- and of PHA-stimulated
      human T-lymphocytes. These effects of IVIgM were observed at non-apoptotic
      concentrations and were stronger on a molar basis than those of normal pooled IgG
      for intravenous use (IVIg). Both preparations, when administered to SCID mice,
      repopulated with human peripheral blood mononuclear cells, delayed the expression
      of the early activation marker CD69 on both human CD4+ and CD8+ T-lymphocytes,
      activated by the mouse antigenic environment. The data obtained show that normal
      pooled human IgM exerts a powerful antiproliferative effect on T-cells that is
      qualitatively similar but quantitatively superior to that of therapeutic IVIg.
      Our results suggest that infusions with IVIgM might have a significant beneficial
      immunomodulating activity in patients with selected autoimmune diseases.

PMID- 16792681
TI  - Attenuated Salmonella typhimurium reduces ovalbumin-induced airway inflammation
      and T-helper type 2 responses in mice.
AB  - Cytokines produced by Th2 cells are responsible for the pathogenesis of asthma.
      Th1-biased immune responses caused by attenuated salmonella have the potential to
      relieve asthmatic symptoms. We evaluated whether oral administration of
      attenuated salmonella could modulate allergic responses in a chicken ovalbumin
      (OVA)-induced asthmatic murine model. Mice were fed with attenuated salmonella
      SL7207 one dose before and three doses during the induction of an allergic
      response. Lung histology, percentages of eosinophil in bronchoalveolar lavage
      fluid, serum levels of OVA-specific antibodies and cytokine production by OVA
      activated splenocytes were evaluated in mice with or without the administration
      of SL7207. A significant reduction in pulmonary eosinophilic infiltration was
      observed in mice receiving attenuated salmonella. Lower levels of OVA-specific
      IgG1 but higher titres of OVA-IgG2a in serum were also detected in this group.
      Splenocytes from salmonella-fed mice produced lower levels of Th2 cytokines upon
      OVA stimulation. The administration of attenuated salmonella significantly
      suppressed immunopathological symptoms in OVA-sensitized mice. Inhibition of Th2
      responses might explain the potential mechanisms. This study provides some
      evidence for the feasibility of attenuated salmonella as an effective vaccine for
      allergic diseases.

PMID- 16792682
TI  - Vaccination with cell immunoglobulin mucin-1 antibodies and inactivated influenza
      enhances vaccine-specific lymphocyte proliferation, interferon-gamma production
      and cross-strain reactivity.
AB  - Influenza virus causes a contagious and potentially serious infection of the
      upper respiratory tract. While neutralizing antibodies are protective against
      infection, the problem of antigenic drift remains, requiring the constant
      monitoring and development of new vaccines. The magnitude of this situation is
      underscored by the emergence of new potentially human pathogenic influenza
      strains, avian H5N1 being the most recent example. We present evidence that
      antibodies against T cell immunoglobulin mucin-1 (TIM-1), a recently identified
      immunomodulatory molecule, stimulate cellular immunity against influenza viruses
      and cross-strain immune reactivity. To determine potential immunostimulatory
      properties of anti-TIM-1, mice were vaccinated with inactivated influenza virus
      in the presence or absence of TIM-1-specific monoclonal antibodies. Development
      of cellular immunity against both the influenza strain used for immunization and
      serotypically distinct virus strains was monitored 3 weeks after vaccination by
      determining antigen-specific lymphocyte proliferation and cytokine production.
      Results show that TIM-1 antibodies enhance antigen-specific cellular
      proliferation (P < 0.05) and interferon (IFN)-gamma production (P < 0.01). Using
      blocking anti-CD4 and CD8 antibodies, it was observed that antigen-specific
      cellular proliferation is CD4-dependent and that the majority of proliferating
      cells are CD4+. Finally, vaccination with inactivated influenza virus with TIM-1
      antibody results in the significant (P < 0.001) induction of proliferation and
      IFN-gamma production upon stimulation with one of three serologically distinct
      strains. TIM-1 antibodies demonstrate an adjuvant effect promoting antigen
      specific cellular proliferation and IFN-gamma production, which are important for
      the promotion of cell-mediated immunity. These results are the first to suggest
      that TIM-1 antibody may serve as a potent adjuvant in the development of new
      influenza virus vaccines.

PMID- 16792683
TI  - Immunostimulatory oligodeoxynucleotide from Bifidobacterium longum suppresses Th2
      immune responses in a murine model.
AB  - We have reported previously that novel immunostimulatory sequence (ISS)
      oligodeoxynucleotide (ODN) BL07S from a probiotic strain of Bifidobacterium
      longum inhibited immunoglobulin (Ig) E production in vitro. However, whether ISS
      ODNs from probiotics regulate T helper type 2 (Th2)-polarized immune reactions in
      vivo remains unclear. To evaluate the inhibitory effects of ODN BL07S on type I
      allergic response, BALB/c mice were injected with or without ODN BL07S in the
      presence of ovalbumin (OVA) on days 0 and 14. Serum Ig levels (IgE, IgG1 and
      IgG2a) and cytokine levels (interferon (IFN)-gamma, interleukin (IL)-12, IL-4, IL
      5, IL-10 and IL-13) were investigated in splenocyte cultures from days 14-28.
      Production of OVA-specific and total IgE were significantly suppressed by
      administration of ODN BL07S, but not by ODN BL06S, a non-ISS-ODN. Compared to
      controls, ODN BL07S induced significantly lower levels of Th2 cytokines (IL-4 and
      IL-5) in splenocyte cultures, and significantly higher levels of serum OVA
      specific IgG2a. These effects of ODN BL07S on modulation of Th2 immune response
      were dose-dependent. The present results demonstrate that ODN BL07S from genomic
      DNA of B. longum BB536 prevents antigen-induced Th2 immune responses in vivo,
      suggesting that ISS-ODNs from probiotics might be useful in preventing allergic
      disease.

PMID- 16792684
TI  - Early apoptosis of monocytes contributes to the pathogenesis of systemic
      inflammatory response and of bacterial translocation in an experimental model of
      multiple trauma.
AB  - The objective of this study was to investigate the occurrence of apoptosis of
      monocytes in an experimental model of multiple trauma and its probable
      correlation to bacterial translocation. Thirty-two rabbits were applied in three
      groups: A, controls; B, myotomy of the right femur; and C, myotomy and fracture
      of the right femur. Blood was sampled for the estimation of endotoxins
      [lipopolysaccharide (LPS)], tumour necrosis factor (TNF)-alpha, malondialdehyde
      (MDA) and isolation of peripheral blood mononuclear cells (PBMCs). PBMCs, derived
      after centrifugation over Ficoll, were incubated in flasks and apoptosis of non
      adherent lymphocytes and adherent monocytes was estimated after staining for
      Annexin-V and flow cytometry. TNF-alpha of supernatants of cultured monocytes was
      also determined. Tissue segments were cultured after death. Median survival of
      groups A, B and C was > 14, > 14 and 9.00 days, respectively. Apoptosis of
      lymphocytes in group C was higher than group A at 2, 4 and 48 h and of monocytes
      in group C higher than group A at 2 and 4 hours. LPS in group C was higher than
      group A at 2, 4 and 48 h. Apoptosis of lymphocytes and monocytes was correlated
      positively with serum TNF-alpha and negatively with TNF-alpha of monocyte
      supernatants. Cultures of organ segments of group A were sterile. Pseudomonas
      aeruginosa was isolated from liver, lung and spleen in five animals in group B
      (45.45%) and in six in group C (54.54%). Early apoptosis of blood monocytes
      supervened after multiple trauma; the phenomenon was accompanied by apoptosis of
      blood lymphocytes and subsequent bacterial translocation.

PMID- 16792685
TI  - Effects of alveolar macrophage depletion on liposomal vaccine protection against
      respiratory syncytial virus (RSV).
AB  - Little is known about the identities and roles of antigen-presenting cells upon
      exposure to antigens of respiratory syncytial virus (RSV). Here, we focused on
      elucidating the importance of alveolar macrophages in conferring protective
      immunity in mice administered a liposome-encapsulated recombinant fragment of the
      RSV G protein. Mice were depleted of alveolar macrophages by intranasal
      inoculation of liposome-encapsulated dichloromethylenediphosphonic acid (DMDP).
      Mice depleted of alveolar macrophages prior to immunization developed reduced
      levels of serum RSV-neutralizing antibody and showed dramatically impaired
      protection against RSV challenge. The severity of interstitial inflammation was
      also markedly reduced in macrophage-depleted mice. In conclusion, this study
      demonstrates a pivotal role for alveolar macrophages during exposure to liposome
      encapsulated RSV antigen in initiating both protective and histopathological
      responses against RSV.

PMID- 16792686
TI  - Variability of the inhibition by total immunoglobulin of in vitro autoantibody
      mediated erythrophagocytosis by mouse macrophages.
AB  - Several autoimmune diseases, mainly autoantibody-mediated, are attenuated by
      infusion of total IgG (IVIg). The efficacy varies widely from one patient to
      another. Using an experimental model of in vitro phagocytosis of autoantibody
      coated erythrocytes by mouse macrophages, we analysed the possible causes for
      such a variability. Our results indicated that the efficacy of the phagocytosis
      inhibition depends upon different factors, such as the isotype and the extent of
      polymerization of the immunoglobulin used for the treatment as well as the
      genetic background of the mice and the state of macrophage activation that can be
      influenced by concomitant viral infection. The development of an in vitro assay
      for the phagocytic activity of macrophages might improve the selection of
      patients susceptible to benefit from IVIg treatment.

PMID- 16792687
TI  - Interleukin (IL)-4 and IL-13 up-regulate monocyte chemoattractant protein-1
      expression in human bronchial epithelial cells: involvement of p38 mitogen
      activated protein kinase, extracellular signal-regulated kinase 1/2 and Janus
      kinase-2 but not c-Jun NH2-terminal kinase 1/2 signalling pathways.
AB  - The Th2 cytokines interleukin (IL)-4 and IL-13 and chemokine monocyte
      chemoattractant protein-1 (MCP-1) are significantly involved in bronchial
      hyperreactivity (BHR) and remodelling in allergic asthma. Although IL-4 and IL-13
      can regulate a number of chemokines from bronchial epithelium, their regulatory
      effect on the expression of MCP-1 is as yet unproved. We aim to investigate the
      intracellular signalling mechanisms of IL-4 and IL-13 regulating the expression
      and secretion of MCP-1 from human bronchial epithelial cells. BEAS-2B cells,
      derived from a human bronchial epithelial cell line, were activated with or
      without IL-4 and/or IL-13 for different time intervals. MCP-1 gene expression and
      protein secretion were measured by reverse transcription-polymerase chain
      reaction and enzyme-linked immunosorbent assay, respectively. Activation of
      signalling molecules p38 mitogen-activated protein kinase (MAPK), extracellular
      signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and Janus kinase-2
      (JAK-2) was accessed by Western blotting. IL-4 and IL-13 were found to up
      regulate gene expression and significantly increase the release of MCP-1 from
      BEAS-2B cells. Both cytokines could activate p38 MAPK, ERK and JAK-2, but not JNK
      activity. Inhibition of p38 MAPK, ERK and JAK-2 activities by pretreating the
      cells with their corresponding inhibitors SB203580, PD98059 and AG490,
      respectively, significantly suppressed IL-4- and IL-13-induced MCP-1 production
      in BEAS-2B cells. Together, the above results illustrate that the activation of
      p38 MAPK, ERK and JAK-2 but not JNK is crucial for IL-4- and IL-13-induced MCP-1
      release in human bronchial epithelial cells. Our findings may provide insight
      into the future development of more effective therapeutic agents for treating
      allergic asthma.

PMID- 16792688
TI  - Hormonal regulation of mannan-binding lectin synthesis in hepatocytes.
AB  - Activation of the complement system via the plasma protein mannan-binding lectin
      (MBL) provides a first line of defence against infections. The plasma level of
      MBL is, in part, determined genetically, but may also be influenced by different
      hormones in vivo. Here we study the hormonal regulation of MBL synthesis from the
      human hepatocyte cell line HuH-7. Cells were exposed to medium with growth
      hormone (GH), hydrocortisone, insulin-like growth factor (IGF)-1, insulin,
      interleukin (IL)-6 or thyroid hormones (T3 or T4). After 3 days the concentration
      of MBL in the culture supernatants was determined and the amount of mRNA for MBL
      was measured, relative to mRNA for beta2 microglobulin. GH, IL-6, T3 and T4
      significantly increased MBL synthesis in a dose-dependent manner, while
      hydrocortisone, insulin and IGF-1 had no effect. T3 caused a fourfold increase at
      1 nM of T3 (P < 0.001) and at 100 nM of T3 the production was increased more than
      eightfold. The effect of T4 was less potent, reaching an eightfold increase at 1
      microM of T4 (P < 0.001). GH augmented the production of MBL threefold at a
      concentration of 100 ng/ml (P = 0.018) with no further effect up to 10 microg/ml,
      whereas IL-6 caused only a very weak increase in MBL production. MBL mRNA levels
      were stable during the first 24 h of T3 stimulation but increased significantly
      between 24 and 48 h. The results suggest that MBL synthesis in humans may be
      increased by thyroid hormone and GH, whereas it does not exhibit a classical IL-6
      dependent response.

PMID- 16792689
TI  - Heat shock proteins form part of a danger signal cascade in response to
      lipopolysaccharide and GroEL.
AB  - An increasing number of cell types, including peripheral blood mononuclear cells
      (PBMCs), have been demonstrated to release heat shock proteins (Hsps). In this
      paper we investigate further the hypothesis that Hsps are danger signals. PBMCs
      and Jurkat cells released Hsp70 (0.22 and 0.7 ng/10(6) cells, respectively) into
      medium over 24 h at 37 degrees C. Release of Hsp70 was stimulated 10-fold by
      GroEL (P < 0.001) and more than threefold by lipopolysaccharide (LPS) (P <
      0.001). Although Hsp60 could be detected in the medium of cells cultured at 37
      degrees C for 24 h, the low rates of release were due probably to cell damage.
      Significant release of Hsp60 was observed when Jurkat cells were exposed to GroEL
      (2.88 ng/10(6) cells) or LPS (1.40 ng/10(6) cells). The data are consistent with
      the hypothesis that Hsp70 and Hsp60 are part of a danger signalling cascade in
      response to bacterial infection.

PMID- 16792691
TI  - CUL4 associates with DDB1 and DET1 and its downregulation affects diverse aspects
      of development in Arabidopsis thaliana.
AB  - Cullins are central scaffolding subunits in eukaryotic E3 ligases that facilitate
      the ubiquitination of target proteins. Arabidopsis contains at least 11 cullin
      proteins but only a few of them have been assigned biological roles. In this work
      Arabidopsis cullin 4 is shown to assemble with DDB1, RBX1, DET1 and DDB2 in vitro
      and in planta. In addition, by using T-DNA insertion and CUL4 antisense lines we
      demonstrate that corresponding mutants are severely affected in different aspects
      of development. Reduced CUL4 expression leads to a reduced number of lateral
      roots, and to abnormal vascular tissue and stomatal development. Furthermore,
      cul4 mutants display a weak constitutive photomorphogenic phenotype. These
      results therefore assign an important function to CUL4 during plant development
      and provide strong evidence that CUL4 assembles together with RBX1 and DDB1
      proteins to form a functional E3 ligase in Arabidopsis.

PMID- 16792690
TI  - Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like
      differentiation of monocytes.
AB  - Monocytes (MO) migrating into normal, non-inflamed intestinal mucosa undergo a
      specific differentiation resulting in a non-reactive, tolerogenic intestinal
      macrophage (IMAC). Recently we demonstrated the differentiation of MO into an
      intestinal-like macrophage (MAC) phenotype in vitro in a three-dimensional cell
      culture model (multi-cellular spheroid or MCS model). In the mucosa of patients
      with inflammatory bowel disease (IBD) in addition to normal IMAC, a reactive MAC
      population as well as increased levels of monocyte chemoattractant protein 1 (MCP
      1) is found. The aim of this study was to investigate the influence of MCP-1 on
      the differentiation of MO into IMAC. MCS were generated from adenovirally
      transfected HT-29 cells overexpressing MCP-1, macrophage inflammatory protein 3
      alpha (MIP-3alpha) or non-transfected controls and co-cultured with freshly
      elutriated blood MO. After 7 days of co-culture MCS were harvested, and
      expression of the surface antigens CD33 and CD14 as well as the intracellular MAC
      marker CD68 was determined by flow-cytometry or immunohistochemistry. MCP-1 and
      MIP-3alpha expression by HT-29 cells in the MCS was increased by transfection at
      the time of MCS formation. In contrast to MIP-3alpha, MCP-1 overexpression
      induced a massive migration of MO into the three-dimensional aggregates.
      Differentiation of IMAC was disturbed in MCP-1-transfected MCS compared to
      experiments with non-transfected control aggregates, or the MIP-3alpha
      transfected MCS, as indicated by high CD14 expression of MO/IMAC cultured inside
      the MCP-1-transfected MCS, as shown by immunohistochemistry and FACS analysis.
      Neutralization of MCP-1 was followed by an almost complete absence of monocyte
      migration into the MCS. MCP-1 induced migration of MO into three-dimensional
      spheroids generated from HT-29 cells and inhibited intestinal-like
      differentiation of blood MO into IMAC. It may be speculated that MCP-1 could play
      a role in the disturbed IMAC differentiation in IBD mucosa.

PMID- 16792692
TI  - Pseudomonas syringae effector AvrPtoB suppresses basal defence in Arabidopsis.
AB  - The virulence and avirulence activities of members of the Pseudomonas syringae
      HopAB family of effectors and AvrPto were examined in bean, tomato and
      Arabidopsis. Proteins were delivered by the RW60 strain of P. syringae pv.
      phaseolicola. RW60 causes a hypersensitive reaction (HR) in bean and tomato but
      is restricted without the HR in Arabidopsis. Dual avirulence and virulence
      functions in tomato and bean, respectively, were identified in virPphA homologues
      but only avrPtoB strongly enhanced virulence to Arabidopsis, overcoming basal
      defences operating against RW60. Virulence activity in both bean and Arabidopsis
      required regions of the C-terminus of the AvrPtoB protein, whereas elicitation of
      the rapid HR in tomato, with the matching Pto resistance gene, did not. The
      effect of AvrPtoB on Arabidopsis was accession-specific; most obvious in
      Wassilewskija (Ws-3), intermediate in Columbia and not detectable in Niedersenz
      (Nd-1) after inoculation with RW60 + avrPtoB. Analysis of crosses between Ws-3
      and Nd-1 indicated co-segregation for the AvrPtoB virulence function with the
      absence of the Nd-1 FLS2 gene which mediates recognition of bacterial flagellin.
      In planta expression of AvrPtoB did not prevent the HR activated by P. syringae
      pv. tomato DC3000 + avrB, avrRpm1, avrRps4 or avrRpt2, but suppressed cell wall
      alterations, including callose deposition, characteristic of basal defence and
      was associated with reprogramming of the plant's transcriptional response. The
      success or failure of AvrPtoB in suppressing basal defences in Nd-1 depended on
      the timing of exposure of plant cells to the effector and the flagellin flg22
      peptide.

PMID- 16792693
TI  - Cloning of two splice variants of the rice PTS1 receptor, OsPex5pL and OsPex5pS,
      and their functional characterization using pex5-deficient yeast and Arabidopsis.
AB  - Using the rice PEX14 cDNA as a bait in a yeast two-hybrid assay, two splice
      variants of the type I peroxisomal targeting signal (PTS1) receptor, OsPex5pL and
      OsPex5pS, were cloned from a pathogen-treated rice leaf cDNA library. The
      proteins were produced from a single gene by alternative splicing, which
      generated a full-length variant, OsPEX5L, and a variant that lacked exon 7,
      OsPEX5S. OsPex5pL contained 11 copies of the pentapeptide motif WXXXF/Y in its N
      terminus, and seven tetratricopeptide repeats in its C-terminus. Expression of
      OsPEX5L and OsPEX5S predominantly occurred in leaf tissues, and was induced by
      various stresses, such as exposure to the pathogen Magnaporthe grisea, and
      treatment with fungal elicitor, methyl viologen, NaCl or hydrogen peroxide. The
      Arabidopsis T-DNA insertional pex5 mutant, Atpex5, which does not germinate in
      the absence of sucrose and was resistant to indole-3-butyric acid (IBA), was
      perfectly rescued by over-expression of OsPex5pL, but not by OsPex5pS. Using
      transient expression of OsPex5pL and OsPex5pS in the Atpex5 mutant, we show that
      OsPex5pL translocates both PTS1- and PTS2-containing proteins into the peroxisome
      by interacting with OsPex7p, whereas OsPex5pS is involved only in PTS1-dependent
      import in Arabidopsis.

PMID- 16792694
TI  - GAMYB controls different sets of genes and is differentially regulated by
      microRNA in aleurone cells and anthers.
AB  - GAMYB is a component of gibberellin (GA) signaling in cereal aleurone cells, and
      has an important role in flower development. However, it is unclear how GAMYB
      function is regulated. We examined the involvement of a microRNA, miR159, in the
      regulation of GAMYB expression in cereal aleurone cells and flower development.
      In aleurone cells, no miR159 expression was observed with or without GA
      treatment, suggesting that miR159 is not involved in the regulation of GAMYB and
      GAMYB-like genes in this tissue. miR159 was expressed in tissues other than
      aleurone, and miR159 over-expressors showed similar but more severe phenotypes
      than the gamyb mutant. GAMYB and GAMYB-like genes are co-expressed with miR159 in
      anthers, and the mRNA levels for GAMYB and GAMYB-like genes are negatively
      correlated with miR159 levels during anther development. Thus, OsGAMYB and
      OsGAMYB-like genes are regulated by miR159 in flowers. A microarray analysis
      revealed that OsGAMYB and its upstream regulator SLR1 are involved in the
      regulation of almost all GA-mediated gene expression in rice aleurone cells.
      Moreover, different sets of genes are regulated by GAMYB in aleurone cells and
      anthers. GAMYB binds directly to promoter regions of its target genes in anthers
      as well as aleurone cells. Based on these observations, we suggest that the
      regulation of GAMYB expression and GAMYB function are different in aleurone cells
      and flowers in rice.

PMID- 16792695
TI  - A putative novel role for plant defensins: a defensin from the zinc hyper
      accumulating plant, Arabidopsis halleri, confers zinc tolerance.
AB  - The metal tolerance of metal hyper-accumulating plants is a poorly understood
      mechanism. In order to unravel the molecular basis of zinc (Zn) tolerance in the
      Zn hyper-accumulating plant Arabidopsis halleri ssp. halleri, we carried out a
      functional screening of an A. halleri cDNA library in the yeast Saccharomyces
      cerevisiae to search for genes conferring Zn tolerance to yeast cells. The
      screening revealed four A. halleri defensin genes (AhPDFs), which induced Zn but
      not cadmium (Cd) tolerance in yeast. The expression of AhPDF1.1 under the control
      of the 35S promoter in A. thaliana made the transgenic plants more tolerant to Zn
      than wild-type plants, but did not change the tolerance to Cd, copper (Cu),
      cobalt (Co), iron (Fe) or sodium (Na). Thus, AhPDF1.1 is able to confer Zn
      tolerance both to yeast and plants. In A. halleri, defensins are constitutively
      accumulated at a higher level in shoots than in A. thaliana. A. halleri defensin
      pools are Zn-responsive, both at the mRNA and protein levels. In A. thaliana,
      some but not all defensin genes are induced by ZnCl2 treatment, and these genes
      are not induced by NaCl treatment. Defensins, found in a very large number of
      organisms, are known to be involved in the innate immune system but have never
      been found to play any role in metal physiology. Our results support the
      proposition that defensins could be involved in Zn tolerance in A. halleri, and
      that a role for plant defensins in metal physiology should be considered.

PMID- 16792696
TI  - Upregulation of an Arabidopsis RING-H2 gene, XERICO, confers drought tolerance
      through increased abscisic acid biosynthesis.
AB  - RING (really interesting new gene) zinc-finger proteins have important regulatory
      roles in the development of a variety of organisms. The XERICO gene encodes a
      small protein (162 amino acids) with an N-terminal trans-membrane domain and a
      RING-H2 zinc-finger motif located at the C-terminus. In silico gene-expression
      analysis indicated that XERICO is induced by salt and osmotic stress. Compared
      with wild-type (WT) Arabidopsis plants, transgenic plants overexpressing XERICO
      (35S::XERICO) exhibited hypersensitivity to salt and osmotic stress and exogenous
      abscisic acid (ABA) during germination and early seedling growth. When subjected
      to a drought treatment, transcriptional upregulation of a key ABA-biosynthesis
      gene, AtNCED3, was much faster and stronger in 35S::XERICO plants compared with
      WT plants. Further, upregulation of XERICO substantially increased cellular ABA
      levels. The adult 35S::XERICO plants, in contrast to early seedling growth,
      showed a marked increase in their tolerance to drought stress. Yeast two-hybrid
      screening indicated that XERICO interacts with an E2 ubiquitin-conjugating enzyme
      (AtUBC8) and ASK1-interacting F-box protein (AtTLP9), which is involved in the
      ABA-signaling pathway. Affymetrix GeneChip array analysis showed that the
      expressions of many of the genes involved in the biosynthesis of plant hormones
      (e.g. ethylene, brassinosteroid, gibberellic acid) were significantly changed in
      the 35S::XERICO plants. These results suggest that the homeostasis of various
      plant hormones might be altered in 35S::XERICO plants, possibly by
      overaccumulation of ABA.

PMID- 16792697
TI  - The CD1d-binding glycolipid alpha-galactosylceramide enhances humoral immunity to
      T-dependent and T-independent antigen in a CD1d-dependent manner.
AB  - Specific interaction of class II/peptide with the T-cell receptor (TCR) expressed
      by class II-restricted CD4+ T helper (Th) cells is essential for in vivo
      production of antibodies reactive with T-dependent antigen. In response to
      stimulation with CD1d-binding glycolipid, Valpha14+ TCR-expressing, CD1d
      restricted natural killer T (NKT) cells may provide additional help for antibody
      production. We tested the hypothesis that the CD1d-binding glycolipid alpha
      galactosylceramide (alpha-GC) enhances production of antibodies reactive with T
      dependent antigen in vivo. alpha-GC enhanced antibody production in vivo in a
      CD1d-dependent manner in the presence of class II-restricted Th cells and induced
      a limited antibody response in Th-deficient mice. alpha-GC also led to
      alterations in isotype switch, selectively increasing production of
      immunoglobulin G2b. Further analysis revealed that alpha-GC led to priming of
      class II-restricted Th cells in vivo. Additionally, we observed that alpha-GC
      enhanced production of antibodies reactive with T-independent antigen, showing
      the effects of NKT cells on B cells independently of Th cells. Our data show that
      NKT cells have multiple effects on the induction of a humoral immune response. We
      propose that NKT cells could be exploited for the development of novel vaccines
      where protective antibody is required.

PMID- 16792699
TI  - Characterization of N-glycosylation consensus sequences in the Kv3.1 channel.
AB  - N-Glycosylation is a cotranslational and post-translational process of proteins
      that may influence protein folding, maturation, stability, trafficking, and
      consequently cell surface expression of functional channels. Here we have
      characterized two consensus N-glycosylation sequences of a voltage-gated K+
      channel (Kv3.1). Glycosylation of Kv3.1 protein from rat brain and infected Sf9
      cells was demonstrated by an electrophoretic mobility shift assay. Digestion of
      total brain membranes with peptide N glycosidase F (PNGase F) produced a much
      faster-migrating Kv3.1 immunoband than that of undigested brain membranes. To
      demonstrate N-glycosylation of wild-type Kv3.1 in Sf9 cells, cells were treated
      with tunicamycin. Also, partially purified proteins were digested with either
      PNGase F or endoglycosidase H. Attachment of simple-type oligosaccharides at
      positions 220 and 229 was directly shown by single (N229Q and N220Q) and double
      (N220Q/N229Q) Kv3.1 mutants. Functional measurements and membrane fractionation
      of infected Sf9 cells showed that unglycosylated Kv3.1s were transported to the
      plasma membrane. Unitary conductance of N220Q/N229Q was similar to that of the
      wild-type Kv3.1. However, whole cell currents of N220Q/N229Q channels had slower
      activation rates, and a slight positive shift in voltage dependence compared to
      wild-type Kv3.1. The voltage dependence of channel activation for N229Q and N220Q
      was much like that for N220Q/N229Q. These results demonstrate that the S1-S2
      linker is topologically extracellular, and that N-glycosylation influences the
      opening of the voltage-dependent gate of Kv3.1. We suggest that occupancy of the
      sites is critical for folding and maturation of the functional Kv3.1 at the cell
      surface.

PMID- 16792700
TI  - Structural study of the catalytic domain of PKCzeta using infrared spectroscopy
      and two-dimensional infrared correlation spectroscopy.
AB  - The secondary structure of the catalytic domain from protein kinase C zeta was
      studied using IR spectroscopy. In the presence of the substrate MgATP, there was
      a significant change in the secondary structure. After heating to 80 degrees C, a
      14% decrease in the alpha-helix component was observed, accompanied by a 6%
      decrease in the beta-pleated sheet; no change was observed in the large loops or
      in 3(10)-helix plus associated loops. The maximum increase with heating was
      observed in the aggregated beta-sheet component, with an increase of 14%. In the
      presence of MgATP, and compared with the sample heated in its absence, there was
      a substantial decrease in the 3(10)-helix plus associated loops and an increase
      in alpha-helix. Synchronous 2D-IR correlation showed that the main changes
      occurred at 1617 cm(-1), which was assigned to changes in the intermolecular
      aggregated beta-sheet of the denaturated protein. This increase was mainly
      correlated with the change in alpha-helix. In the presence of MgATP, the main
      correlation was between aggregated beta-sheet and the large loops component. The
      asynchronous 2D-correlation spectrum indicated that a number of components are
      transformed in intermolecularly aggregated beta-sheet, especially the alpha-helix
      and beta-sheet components. It is interesting that changes in 3(10)-helix plus
      associated loops and in alpha-helix preceded changes in large loops, which
      suggests that the open loops structure exists as an intermediate state during
      denaturation. In summary, IR spectroscopy revealed an important effect of MgATP
      on the secondary structure and on the thermal unfolding process when this was
      induced, whereas 2D-IR correlation spectroscopy allowed us to show the
      establishment of the denaturation pathway of this protein.

PMID- 16792698
TI  - A T2 cytokine environment may not limit T1 responses in human immunodeficiency
      virus patients with a favourable response to antiretroviral therapy.
AB  - Low-level production of interferon-gamma (IFN-gamma) marks human immunodeficiency
      virus (HIV)-induced immunodeficiency and has been ascribed to a bias towards T2
      cytokines. This was investigated in two cross-sectional studies of HIV patients
      who were immunodeficient when they began antiretroviral therapy (ART) and had
      stable increases in CD4 T-cell counts. Blood leucocytes were assessed
      unstimulated or after stimulation with cytomegalovirus (CMV), anti-CD3 or
      mitogen. IFN-gamma and interleukin (IL)-5 responses were initially assessed by
      enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) and enzyme-linked
      immunosorbent assay (ELISA). We then adopted a sensitive reverse transcription
      polymerase chain reaction (RT-PCR) system to assess IFN-gamma, IL-5, IL-4 and IL
      4delta2 (an inhibitory splice variant of IL-4) mRNA. The results were correlated
      with putative serological markers of a T1 [lymphocyte activation gene-3 (LAG-3),
      CD26] or a T2 [CD30, immunoglobulin E (IgE)] cytokine environment. IL-5
      production and IgE levels were elevated in patients. IgE levels did not correlate
      with IFN-gamma, but showed an inverse correlation with IL-5 released in culture
      (P = 0.05). The levels of IL-4, IFN-gamma, IL-5 and IL-4delta2 mRNA were
      correlated after anti-CD3 stimulation, where IL-5 was the best predictor of IFN
      gamma mRNA (P = 0.006). Weak positive correlations were evident between CD30 and
      cytokine mRNA levels, whilst IgE correlated inversely with IL-4, IL-4delta2, IL-5
      and IFN-gamma mRNA levels. These analyses provide no evidence for an inverse
      relationship between T1 and T2 cytokine responses in HIV patients, but suggest
      that the elevation of IgE marks low cytokine responses.

PMID- 16792702
TI  - Inhibitory effects of nontoxic protein volvatoxin A1 on pore-forming cardiotoxic
      protein volvatoxin A2 by interaction with amphipathic alpha-helix.
AB  - Volvatoxin A2, a pore-forming cardiotoxic protein, was isolated from the edible
      mushroom Volvariella volvacea. Previous studies have demonstrated that volvatoxin
      A consists of volvatoxin A2 and volvatoxin A1, and the hemolytic activity of
      volvatoxin A2 is completely abolished by volvatoxin A1 at a volvatoxin
      A2/volvatoxin A1 molar ratio of 2. In this study, we investigated the molecular
      mechanism by which volvatoxin A1 inhibits the cytotoxicity of volvatoxin A2.
      Volvatoxin A1 by itself was found to be nontoxic, and furthermore, it inhibited
      the hemolytic and cytotoxic activities of volvatoxin A2 at molar ratios of 2 or
      lower. Interestingly, volvatoxin A1 contains 393 amino acid residues that closely
      resemble a tandem repeat of volvatoxin A2. Volvatoxin A1 contains two pairs of
      amphipathic alpha-helices but it lacks a heparin-binding site. This suggests that
      volvatoxin A1 may interact with volvatoxin A2 but not with the cell membrane. By
      using confocal microscopy, it was demonstrated that volvatoxin A1 could not bind
      to the cell membrane; however, volvatoxin A1 could inhibit binding of volvatoxin
      A2 to the cell membrane at a molar ratio of 2. Via peptide competition assay and
      in conjunction with pull-down and co-pull-down experiments, we demonstrated that
      volvatoxin A1 and volvatoxin A2 may form a complex. Our results suggest that this
      occurs via the interaction of one molecule of volvatoxin A1, which contains two
      amphipathic alpha-helices, with two molecules of volvatoxin A2, each of which
      contains one amphipathic alpha-helix. Taken together, the results of this study
      reveal a novel mechanism by which volvatoxin A1 regulates the cytotoxicity of
      volvatoxin A2 via direct interaction, and potentially provide an exciting new
      strategy for chemotherapy.

PMID- 16792705
TI  - Breastfeeding: how some things have stayed the same.

PMID- 16792701
TI  - Characterization of myo-inositol hexakisphosphate deposits from larval
      Echinococcus granulosus.
AB  - The abundant metabolite myo-inositol hexakisphosphate (InsP6) can form vesicular
      deposits with cations, a widespread phenomenon in plants also found in the
      cestode parasite, Echinococcus granulosus. In this organism, the deposits are
      exocytosed, accumulating in a host-exposed sheath of extracellular matrix termed
      the laminated layer. The formation and mobilization of InsP6 deposits, which
      involve precipitation and solubilization reactions, respectively, cannot yet be
      rationalized in quantitative chemical terms, as the solids involved have not been
      formally described. We report such a description for the InsP6 deposits from E.
      granulosus, purified as the solid residue left by mild alkaline digestion of the
      principal mucin component of the laminated layer. The deposits are largely
      composed of the compound Ca5H2L.16H2O (L representing fully deprotonated InsP6),
      and additionally contain Mg2+ (6-9% molar ratio with respect to Ca2+), but not
      K+. Calculations employing recently available chemical constants show that the
      precipitation of Ca5H2L.16H2O is predicted by thermodynamics in secretory vesicle
      like conditions. The deposits appear to be similar to microcrystalline solids
      when analysed under the electron microscope; we estimate that each crystal
      comprises around 200 InsP6 molecules. We calculate that the deposits increase, by
      three orders of magnitude, the surface area available for adsorption of host
      proteins, a salient ability of the laminated layer. The major inositol phosphate
      in the deposits, other than InsP6, is myo-inositol (1,2,4,5,6) pentakisphosphate,
      or its enantiomer, inositol (2,3,4,5,6) pentakisphosphate. The compound appears
      to be a subproduct of the intracellular pathways leading to the synthesis and
      vesicular accumulation of InsP6, rather than arising from extracellular
      hydrolysis of InsP6.

PMID- 16792707
TI  - Testosterone for women: necessary or noxious?

PMID- 16792708
TI  - Pregnancy, lactation and nipple piercings.

PMID- 16792709
TI  - Patient safety. Expert roundtable discussion.

PMID- 16792710
TI  - Embracing the role of the advanced practice nurse in the perinatal setting.

PMID- 16792712
TI  - It's the journey, not the destination. Grief and its complications.

PMID- 16792711
TI  - Waardenburg syndrome. "S.E.E." how nurses can intervene.

PMID- 16792713
TI  - How to bring evidence into your practice.

PMID- 16792714
TI  - The contraceptive patch. Latest developments.

PMID- 16792715
TI  - Skills and competencies for today's nurse executive.

PMID- 16792717
TI  - When nurse becomes patient.

PMID- 16792718
TI  - Fraud in scientific publishing.

PMID- 16792720
TI  - Mucoepidermoid carcinoma of minor salivary glands: a clinical study of 16 cases
      and review of the literature.
AB  - OBJECTIVE: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of
      salivary glands with a widely diverse biologic behavior that is correlated with
      the histological grade of the tumor. The purpose of this study was to evaluate
      the clinical outcomes of MEC of minor salivary glands in a group of 16 patients,
      who were treated in our clinic, and to discuss the management of this carcinoma.
      MATERIALS AND METHODS: Between 1985 and 2000, 16 patients with MEC of minor
      salivary glands were treated in the Clinic of Oral and Maxillofacial Surgery of
      the 'G. Papanikolaou' General Hospital, in Thessaloniki. The age range was 16-65
      years. The distribution of the primary sites was: hard plate (one), soft palate
      (two), hard and soft palate (three), hard and soft palate with spread in
      paranasal sinus and nasal cavity (one), buccal mucosa (three), hard palate,
      alveolar process and buccal mucosa (two), and retromolar triangle (our). The
      tumors were clinically staged according to the tumor nodes metastase (TNM) system
      (Seifert, 1991). All patients were treated radically with surgery. The surgery
      was combined with radiotherapy in nine patients. Radiotherapy was delivered using
      Co-60. Doses ranged from 50 to 60 Gy and the duration of the therapy ranged from
      25 to 35 days. Immunohistochemical assay of the expression of the Ki-67 antigen
      was performed on a subset of 15 cases. RESULTS: The mean follow-up range was 4-14
      years. From the 16 patients with MECs 10 (62.5%) were alive and five (35.6%) had
      died from the disease. Four patients were free of the disease for more than 5
      years (range 8-14), five patients were free of the disease for 5 years and one
      patient was free of the disease for 4 years. One patient lived more than 10 years
      and died from another cause. Local recurrence developed in one patient 10 years
      after the initial treatment. Lymph node metastases occurred in one patient within
      the first year after the initial surgical treatment. Distant metastases (two in
      bones and one in lungs) occurred in three patients within 2 years after
      completing the treatment. The Pearson chi-square statistical analysis was used
      for comparing the Ki-67 values in correlation with histological grade of the
      tumors. The Ki-67 expression was only 1% in low-grade MECs, while in intermediate
      grade tumors it was estimated between 3 and 4%. The high-grade tumors had
      increased expression (10%) of tumor cells. CONCLUSION: Complete surgical excision
      is the treatment of choice for MECs. Adequate excision is important in all grades
      of tumors. Prognosis of MECs is a function of the histological grade, adequacy of
      excision and clinical staging. The immunohistochemical study of Ki-67 expression
      may provide additional prognostic information for this tumor.

PMID- 16792719
TI  - Stem cells in the periodontal ligament.
AB  - The ability to identify and manipulate stem cells has been a significant
      advancement in regenerative medicine and has contributed to the development of
      tissue engineering-based clinical therapies. Difficulties associated with
      achieving predictable periodontal regeneration, means that novel techniques such
      as tissue engineering need to be developed in order to regenerate the extensive
      soft and hard tissue destruction that results from periodontitis. One of the
      critical requirements for a tissue engineering approach is the delivery of ex
      vivo expanded progenitor populations or the mobilization of endogenous progenitor
      cells capable of proliferating and differentiating into the required tissues. By
      definition, stem cells fulfill these requirements and the recent identification
      of stem cells within the periodontal ligament represents a significant
      development in the progress toward predictable periodontal regeneration. In order
      to explore the importance of stem cells in periodontal wound healing and
      regeneration, this review will examine contemporary concepts in stem cell
      biology, the role of periodontal ligament progenitor cells in the regenerative
      process, recent developments in identifying periodontal stem cells and the
      clinical implications of these findings.

PMID- 16792721
TI  - Association of uncultivated oral phylotypes AU126 and X112 with periodontitis.
AB  - OBJECTIVE: To discuss the relationship between uncultivated pathogenic bacteria
      and periodontitis. SUBJECTS AND METHODS: Specific polymerase chain reaction (PCR)
      primers were designed for phylotypes AU126 and X112; PCRs were applied to
      determine the prevalence of these phylotypes in 35 patients with chronic
      periodontitis, 26 patients with plaque-induced gingivitis and 20 healthy control
      subjects. RESULTS: The specificity of each primer is validated on the basis of
      the results from sequence analysis of PCR products. AU126 and X112 were detected
      in the subgingival plaque samples in all the three groups. The prevalence of
      AU126 in subgingival plaque in chronic periodontitis (77.1%) and plaque-induced
      gingivitis (61.5%) is relatively higher than that in the healthy subjects
      (10.0%), and the difference is statistically significant (P < 0.01). The
      prevalence of X112 in subgingival plaque in periodontitis patients (85.7%) is
      higher than that in healthy subjects (30.0%), the difference (P < 0.01) being
      equally statistically significant. The difference between the chronic
      periodontitis group and the plaque-induced gingivitis group (50.0%) is
      statistically significant (P < 0.05). CONCLUSIONS: It might be assumed that the
      novel uncultivated AU126 phylotype could possibly be related to chronic
      periodontitis and plaque-induced gingivitis, and that X112 might play a role in
      the progress of lesion from gingivitis to periodontitis.

PMID- 16792722
TI  - Separation, cultivation and biological characteristics of oral carcinoma
      associated fibroblasts.
AB  - OBJECTIVES: Carcinoma-associated fibroblasts (CAFs) have been suggested to
      regulate the initiation and progression of many types of solid tumors. The aim of
      the study was to separate, cultivate, identify oral CAFs, and to investigate
      their biological characteristics. MATERIALS AND METHODS: The primary CAFs and
      normal fibroblasts (NFs) of the tongue were obtained by tissue culture. Then
      cells were dissociated by 0.25% trypsin and purified by curettage method
      combining with trypsinization. The cells were verified according to morphological
      observation and immunohistochemical staining of certain proteins. Multiple
      proliferation indexes and karyotype of the cells were assayed. RESULTS: Third
      passage purified oral CAFs and NFs were attained successfully. The morphological
      characteristics of the CAFs changed significantly comparing to the NFs. The CAFs
      showed positive staining for vimentin, alpha-smooth muscle actin and matrix
      metalloproteinases-2. The proliferation and mitosis ability of the CAFs were
      significantly increased compared with the NFs (P < 0.05). No karyotypic
      abnormalities were found in the CAFs. CONCLUSIONS: There were obvious differences
      in the biological characteristics between oral CAFs and NFs. The results may
      provide us an experimental foundation for further studies on the roles of CAFs in
      the initiation and progression of oral cancer.

PMID- 16792723
TI  - Prevalence and risk factors associated with geographic tongue among US adults.
AB  - OBJECTIVE: To characterize the prevalence of geographic tongue (GT) among US
      adults. DESIGN: Population-based case-control study. MAIN OUTCOME MEASURES: The
      presence or absence of GT. SUBJECTS AND METHODS: Data from 16 833 adults examined
      during The Third National Health and Nutrition Examination Survey, 1988-1994
      (NHANES III), a study based on multistage probability sampling were analyzed
      using SAS-callable SUDAAN 9.0.1. RESULTS: Geographic tongue point prevalence was
      1.8% (95% CI: 1.4, 2.3). Multivariate logistic regression showed significant
      effects of race-ethnicity, with Whites (AOR = 1.8; 1.3, 2.5) and Blacks (AOR =
      1.6; 1.2, 2.1) having greater odds of GT than Mexican-Americans; current
      corticosteroid therapy (AOR = 3.7; 1.54, 8.6). Cigarette smokers had lower GT
      prevalence (AOR = 0.4; 0.3, 0.6). Fissured tongue (FT) was strongly associated
      with GT among non-smokers: AOR = 17.5 (7.8, 39.5). We did not find significant
      associations with age, gender, oral contraceptive use, diabetes mellitus, allergy
      or atopy, psychological or dermatological conditions as previous research has
      suggested. CONCLUSIONS: Geographic tongue was more prevalent among Whites and
      Blacks compared with Mexican-Americans, positively associated with FT, and
      inversely associated with cigarette smoking.

PMID- 16792724
TI  - The induction of oral tolerance to Actinomyces viscosus in mice.
AB  - OBJECTIVES: To determine whether oral tolerance with the oral bacterium
      Actinomyces viscosus was inducible in mice. MATERIALS AND METHODS: Mice were
      intragastrically (i.g.) and then intraperitoneally (i.p.) immunized with heat
      killed A. viscosus. A control group of mice received only saline. A delayed type
      hypersensitivity (DTH) response and the levels of isotype specific antibodies
      were assessed. Spleen cells from mice that were i.g. immunized with A. viscosus
      were transferred to A. viscosus-primed mice in vivo and in vitro. Furthermore,
      mice were i.g. immunized with saline or A. viscosus and then challenged i.p. with
      saline, A. viscosus, or Porphyromonas gingivalis. RESULTS: Intragastric
      immunization with A. viscosus suppressed both DTH and serum specific antibodies
      to A. viscosus. DTH suppression lasted until week 4, while serum immunoglobulin
      (Ig)A and both IgG and IgM specific antibody levels remained suppressed up to
      week 8 and 12 respectively. IgG specific antibody suppression was transferable.
      The DTH response and serum antibodies specific to A. viscosus were suppressed in
      mice after i.g. challenged with A. viscosus but not P. gingivalis. CONCLUSION:
      Mucosal presentation of A. viscosus in mice led to the suppression of immune
      response to this bacterium in an antigen-specific fashion. Tolerance of DTH
      response was short lived, while suppression of antigen-specific IgG antibodies in
      mucosally tolerized mice was long-lasting.

PMID- 16792725
TI  - Tooth survival and periodontal tissues healing of allogenic-transplanted teeth in
      the mice.
AB  - OBJECTIVE: For the successful organ transplantation, immune rejection has to be
      considered. Autogenic transplantation of human teeth is generally carried out
      free of clinical difficulty because of the lack of immune reaction, whereas
      allogenic tooth transplantations easily induce host immune rejection to donor
      tissues. The aim of the present study was to evaluate the replacement of donor
      tissue by host cells after allogenic tooth transplantation. MATERIALS AND
      METHODS: First molars extracted from lacZ transgenic ROSA26 mice were
      transplanted into the alveolar socket and the tongue of host wildtype mice, where
      the first molar had existed. RESULTS: Donor cells from lacZ transgenic mice were
      not detected in the periodontal ligament space, but rather in the pulp chamber of
      the donor tooth. Furthermore, if the pulp chamber was widely open to an affluent
      blood supply, odontoblasts and fibroblasts in the donor tissue survived in the
      dental pulp. CONCLUSIONS: Our experimental models using lacZ transgenic ROSA26
      mice clearly demonstrate that donor periodontal tissue cells are replaced by host
      cells and that periodontal tissue can regenerate after allogenic tooth
      transplantation. Furthermore, our models suggest that donor pulpal cells can
      survive if the vascular supply into the pulp chamber is sufficient.

PMID- 16792726
TI  - Oral candidosis and oral hairy leukoplakia as predictors of HAART failure in
      Brazilian HIV-infected patients.
AB  - INTRODUCTION: Oral candidosis (OC) and hairy leukoplakia (OHL) are important
      markers of Human Immunodeficiency Virus (HIV) infection immune status.
      OBJECTIVES: to evaluate if OC and/or OHL should be considered clinical predictors
      of immune and virologic failure on HIV-infected Brazilian adults undergoing
      Highly Active Antiretroviral Therapy (HAART). METHODS: 124 HIV-infected patients
      who used HAART for a minimum of six months were prospectively evaluated. All of
      them under-took oral examination and serum CD4+ count and viral load (VL), being
      divided in two groups, P and A, respectively according to the presence or absence
      of OC and/or OHL. During a six month period, patients belonging to group A were
      followed. They were re-examined for new oral lesions. New blood samples were
      collected and they were subdivided into groups P6 and A6. CD4+ count and VL were
      compared between groups at baseline and after the six months period. Sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV) and
      relative risk (RR) were obtained in order to assess the accuracy of using OC and
      OHL as predictors of immune and virologic failure, at baseline and after a six
      month period. RESULTS: At baseline and after six months, patients with OC and OHL
      have mean CD4+ count lower and mean VL higher than patients of group A and A6 (p
      < 0.001). OC had high PPV for immune failure and a moderated PPV for virologic
      failure. OHL had low PPVs for both measures. DISCUSSION AND CONCLUSIONS: OC and
      OHL still indicate low serum CD4+ count and high VL, but OC seems to be a better
      predictor of immune and virologic failure in patients undergoing HAART than OHL.

PMID- 16792727
TI  - Dynamic magnetic resonance sialography as a new diagnostic technique for patients
      with Sjogren's syndrome.
AB  - OBJECTIVE: To evaluate the clinical utility of dynamic magnetic resonance (MR)
      sialographic images as a diagnostic tool for patients with Sjogren's syndrome.
      METHODS: The morphological findings and various kinds of functional parameters in
      volunteers on dynamic MR sialographic images were compared with those in five
      patients with definite Sjogren's syndrome. RESULTS: On the MR sialographs of all
      five patients with Sjogren's syndrome, the so-called 'apple-tree appearance' was
      seen. The difference in two functional parameters using the dynamic MR
      sialographic data was elucidated between the two groups. The maximum area of the
      detectable ducts in the group of patients was significantly smaller (P < 0.001)
      than that in the group of volunteers. The ratio of change in the detectable ducts
      in the group of patients was significantly lower (P = 0.011) than that in the
      group of volunteers. CONCLUSIONS: Our study suggests that dynamic MR sialographic
      data in addition to MR sialographic images might be useful for the diagnosis of
      Sjogren's syndrome.

PMID- 16792728
TI  - Influence of administration methods on the accumulation of ALA-induced Pp-IX in
      mouse tongue tumors.
AB  - OBJECTIVE: 5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has been
      used as a photosensitizer in photodynamic therapy (PDT) for oral cancer. This
      study investigates the optimal method of administrating ALA by analyzing PpIX
      fluorescence in tongue tumor tissue. METHODS: Protoporphyrin IX intensities in
      the mouse (C3H)-transplanted tongue cancer (NR-S1) were compared with those in
      normal tongue after intraperitoneal (i.p.), oral (p.o.) or topical administration
      of ALA. Tongues were sampled at various times after ALA administration. PpIX
      intensities were obtained from frozen sections of each sample by using a
      spectrophotometer. RESULTS: Protoporphyrin IX intensity in the tumor group peaked
      at 3 h after the i.p. and 5 h after the p.o. administration of ALA, and these
      levels were about twice as high as those in the normal group. Maximum PpIX
      accumulation in the tongue tumor tissue was seen at 5 h after p.o. administration
      of ALA. In contrast, the topical administration of 20% ALA cream was associated
      with the lowest PpIX accumulation in the tumor throughout the experiments.
      CONCLUSION: These results suggested that p.o. administration of ALA was the most
      effective method in ALA-PDT for oral cancer.

PMID- 16792729
TI  - The distribution of oral mucosal pH values in healthy saliva secretors.
AB  - OBJECTIVES: To establish the normal range of oral mucosal pH and to correlate
      these measurements to salivary flow rate in healthy individuals according to age
      and gender. SUBJECTS AND METHODS: Measurements of pH levels using a flat pH meter
      and salivary secretion rates were established in eight mucosal sites from a total
      of 50 healthy individuals. RESULTS: The mean pH (+/-s.d.) of all sites was 6.78
      +/- 0.04 with significant differences between mean pH values in the palate (7.34
      +/- 0.38), the floor of the mouth (6.5 +/- 0.3), the buccal mucosa (6.28 +/-
      0.36) and the tongue (6.8 +/- 0.26). A significant correlation was found between
      age and pH at palatal and tongue sites but no gender effects were noted.
      CONCLUSIONS: This method is easy and relatively quick to manipulate, and may
      offer many diagnostic possibilities for oral related diseases and disorders such
      as oral malodour, mouth breathing, dysgeusia, acidic diet consumption and
      gastrointestinal disorders affecting the mouth.

PMID- 16792730
TI  - The homeobox HOXB13 is expressed in human minor salivary gland.
AB  - BACKGROUND: Homeobox are a family of developmental genes involved in
      morphogenesis and cellular differentiation. Participation of homeobox within
      normal and malignant tissue has been recently discussed in the literature.
      OBJECTIVE: To analyze the presence of HOXB13 transcript expression in human minor
      salivary gland. MATERIAL AND METHODS: Ten-micrometer sections from frozen samples
      were evaluated employing non-radioactive in situ hybridization technique and
      HOXB13 mRNA probes. RESULTS: HOXB13 was found to be expressed in ducts and mucous
      acini but not in serous acini. CONCLUSIONS: RESULTS suggest that HOXB13
      transcripts are differently expressed in normal mucous and serous acini, and it
      may possibly reflect a different role in salivary gland carcinogenesis.

PMID- 16792733
TI  - Fluconazole and/or hexetidine for management of oral candidiasis associated with
      denture-induced stomatitis.

PMID- 16792731
TI  - Specificity of the monoclonal antibody 3H8 in the immunohistochemical
      identification of Candida species.
AB  - Candida albicans has been shown to be involved in the pathogenesis of adult
      periodontitis (AP). The diagnosis of Candida-associated AP depends largely on the
      identification of yeast and pseudomycelial forms in gingival tissue samples by
      using periodic acid-Schiff and Gomori methenamine silver stains. However, these
      stains are non-specific and also reveal confusing artifacts seemingly rather
      difficult to distinguish from yeasts. With the recent development and
      availability of monoclonal antibodies (Mabs) to various epitopes of C. albicans,
      for example Mab 3H8 which recognizes a mannoprotein, it is now possible to
      identify Candida in human tissue biopsies. To explore further the usefulness of
      this Mab in detecting Candida in periodontal disease the antibody was tested
      against a wide range of yeast species and strains and various morphological
      forms, grown in agar blocks at various temperatures and for various time periods.
      Furthermore, considering the location of the 3H8 epitope on the external cell
      wall of certain C. albicans strains, it seemed reasonable to determine whether
      the epitope could be expressed into the surrounding environment, further aiding
      the recognition of the organism in tissue. The 3H8 epitope appeared to be located
      at the external surface and on the septum between the mother cell and germ tube
      of some C. albicans strains but it was partially cryptic in the cell wall of
      other strains. Both yeast blastoconidia and pseudohyphae were labeled by the 3H8
      antibody. Candida lusitaniae, C. glabrata, C. krusei, C. parapsilosis and C.
      tropicalis did not posses the epitope. The epitope was expressed extracellularly
      by both blastoconidia and pseudohyphae of C. albicans. This Mab appears to be
      suitable for the identification of C. albicans in periodontal tissue and may
      provide further insight into the role of C. albicans in the pathogenesis and
      diagnosis of periodontal diseases.

PMID- 16792734
TI  - Fusidic acid viscous eyedrops--an evaluation of pharmacodynamics,
      pharmacokinetics and clinical use for UK optometrists.
AB  - Recent changes in UK law have allowed UK-based optometrists to sell and supply
      fusidic acid viscous eyedrops, providing it is in the course of their
      professional activity and in an emergency. Alternatively, the optometrist may
      access fusidic acid viscous eyedrops, for a named patient, using a written order
      supplied to a pharmacy. This review provides details of the legal background to
      these changes, examines the common causes of a bacterial conjunctivitis, examines
      the mechanism of action of this narrow spectrum antibiotic as a bacteriostatic
      agent, reviews the susceptibility of common ocular isolates of bacteria to the
      drug and presents details of the expected pharmacokinetics of the viscous
      eyedrops. From this perspective, a systematic review is provided of the clinical
      studies which have investigated the use of fusidic acid viscous eyedrops and
      their outcome. The indicated use is generally for the treatment of bacterial
      conjunctivitis and/or blepharoconjunctivitis, especially that caused by
      Staphylococcus, but not Streptococcus or Haemophilus sp. (more likely associated
      with concurrent nasopharyngeal infections). The usual regimen for use is twice
      daily for 5-10 days, depending on severity, and can initially be used more
      intensively (four times per day). It may also be used for the management of
      corneal and conjunctival abrasions and foreign body injuries, or some cases of
      chronic blepharitis.

PMID- 16792735
TI  - Supplementation with the carotenoids lutein or zeaxanthin improves human visual
      performance.
AB  - BACKGROUND: Macular pigment (MP) is found in diurnal primate species when vision
      spans a range of ambient illumination and is mediated by cone and rod
      photoreceptors. The exact role of MP remains to be determined. In this study we
      investigate two new hypotheses for possible MP functions. OBJECTIVE: As MP
      absorption coincides partly with that of rhodopsin, MP may reduce rod signal
      effectiveness in the mesopic range, thus extend the usefulness of cone-mediated
      vision into the mesopic range. Forward light scatter in the eye can reduce
      retinal image contrast. If blue light contributes significantly to intraocular
      scatter, selective blue light absorption by MP could reduce the effects of
      scatter. DESIGN: We investigated 34 subjects from a carotenoid supplementation
      trial. The measurements included high mesopic contrast acuity thresholds (CATs),
      macular pigment optical density (MPOD), wavefront aberrations, and scattered
      light. The measurements were made after 6 months of daily supplementation with
      zeaxanthin (Z, OPTISHARP), lutein (L), a combination of the two (C), or placebo
      (P), and again after a further 6 months of doubled supplementation. RESULTS: The
      data reveal a trend toward lower CATs in all groups supplemented, with a
      statistically significant improvement in the lutein group (p = 0.001), although
      there was no correlation with MPOD. Light scattering in the eye and the root-mean
      square wavefront aberrations show decreasing trends as a result of
      supplementation, but no correlation with MPOD. CONCLUSIONS: The results suggest
      that supplementation with L or Z increases MPOD at the fovea and at 2.5 degrees ,
      and that supplementation can improve CATs at high mesopic levels and hence visual
      performance at low illumination.

PMID- 16792736
TI  - Grading infantile cataracts.
AB  - PURPOSE: To introduce and describe two methods of grading the severity of
      infantile cataracts, and thereby propose a useful clinical guide for early
      surgical intervention. METHODS: Thirty-three subjects, aged 1 week to 8 years,
      participated in the study. Twenty-two were evaluated soon after birth (1 week),
      and 11 in childhood (3-8 years). All had isolated infantile cataracts, of which
      16 were bilateral and 17 unilateral. Nine cataract types were examined; nuclear
      (n = 9), lamellar (n = 9), posterior lenticonus (n = 4), persistent hyperplastic
      primary vitreous (n = 4), posterior polar (n = 3) and single cases of total,
      cortical, sutural and anterior polar. Grading the infantile cataracts was
      performed subjectively based on the cataract morphology, density and position
      using an 11-point (0-10) ordinal scale. Objective measures of the cataracts were
      performed by scanning and then digitising photo-slit lamp images to provide
      cataract intensity profiles. Subjects without cataracts acted as controls.
      RESULTS: Subjective gradings of 0 and 10 were assigned to the clear, cataract
      free lens and the total cataract, respectively. Fixed grades of 1 (anterior
      polar, sutural) and 6 (posterior polar) were assigned to the three remaining
      cataracts with static morphologies. The five cataracts which were all progressive
      were given grading ranges, reflecting the initial and likely final morphological
      states. Objective measures were found to be valuable in indicating the exact
      position and relative density of the cataract, as well as accurately defining
      boundaries. CONCLUSIONS: The magnitude and severity of infantile cataracts can be
      usefully characterised by an 11-point ordinal subjective grading scale. Although
      subjective grading alone is satisfactory, it can be greatly assisted by objective
      measures, particularly in the documentation of cataract progression. Cataracts
      assigned grades 1-4 were considered minor obstructions to vision and therefore
      not candidates for early surgery. Cataracts graded 5 and above were considered
      major visual defects, and ideally should be removed early in life.

PMID- 16792737
TI  - The exponential-mean-log-transference as a possible representation of the optical
      character of an average eye.
AB  - Considering a set of eyes, how does one define an average whose optical character
      represents an average of the optical characters of the eyes in the set? The
      recent proposal of the exponential-mean-log-transference was based on a
      conjecture. The purpose of this note is to provide justification by proving the
      conjecture and defining the conditions under which it fails.

PMID- 16792739
TI  - Visual impairment and the useful field of vision.
AB  - The aim of this study was to measure the useful field of vision (UFoV) in people
      with visual impairment and to compare results with clinical measures of vision.
      UFoV, visual acuity, contrast sensitivity and visual fields were measured in 36
      participants with low vision and 22 age-matched controls in two age groups. For
      both the low vision and control groups the presence of distractors (cluttered
      field) increased the error rates on our UFoV measure but there was no significant
      effect of the presence of a central task (divided attention). Participants with
      low vision made more errors on UFoV than did controls, but this difference
      disappeared once their visual field defects were accounted for. By multiple
      regression analysis, age, visual fields and contrast sensitivity were shown to
      predict the different UFoV scores. As for observers with normal vision, standard
      clinical visual field tests may not fully describe the difficulties that may be
      encountered by people with visual impairment undertaking tasks in the cluttered
      environments and multiple demands of everyday life.

PMID- 16792738
TI  - Non-contact tonometry synchronized with cardiac rhythm and its relationship with
      blood pressure.
AB  - PURPOSE: The main objectives of this study were to determine the differences
      between non-synchronized intraocular pressure (IOP_N) and intraocular pressure
      readings synchronized with cardiac pulse and try to determine if these parameters
      are related to blood pressure values. METHODS: One hundred and sixty-five right
      eyes from 165 volunteers (107 females, 58 males) aged from 19 to 73 years (mean
      +/- S.D., 29.93 +/- 11.17) were examined with the Nidek NT-4000, a new non
      contact tonometer that allows the measurement of IOP synchronized with the
      cardiac rhythm. IOP measurements in the four different modes of synchronization
      were taken in a randomized order. Three measures of each parameter were taken and
      then averaged. The blood pressure was determined three times with a portable
      manometer and mean values of systolic and diastolic pressure and the pulse rate
      were computed. Mean arterial pressure (MAP) was determined as being 1/3 of
      systolic plus 2/3 of diastolic blood pressure. RESULTS: The mean +/- S.D. values
      for the standard intraocular pressure (IOP_N: 14.76 +/- 2.86), intraocular
      pressure in the systolic instant or peak (IOP_P: 14.99 +/- 2.85), intraocular
      pressure in the middle instant between heartbeats or middle (IOP_M: 14.68 +/-
      2.76), and intraocular pressure in the diastolic instant or bottom (IOP_B: 13.86
      +/- 2.61) were obtained. The IOP_P was higher than the remaining values. A
      significant difference in mean IOP existed between IOP_B and the remaining modes
      of measuring (p < 0.05). Differences were statistically significant for all pair
      comparisons involving IOP_B. Arterial blood pressure values were systolic 125.5
      +/- 14.22, diastolic 77.7 +/- 8.38 and MAP 93.64 +/- 9.44 mmHg. The pulse rate
      was 77.3 +/- 12.6 beats per minute. Except for the MAP (p = 0.025) there was no
      significant correlation between different IOP values and systolic or diastolic
      blood pressure, or pulse rate. CONCLUSIONS: NT-4000 is able to differentiate IOP
      values when synchronized with the cardiac rhythm and those differences are
      expected to be within a range of +/-2.5 to +/- 3.0 mmHg. IOP_B seems to be the
      parameter whose value differs from the non-synchronized and the remaining
      synchronized parameters in a significant way. Other than a weak association with
      MAP, no significant correlation between IOP and BP was found. The measurements of
      IOP readings for the three modes are consistent with timings during the cardiac
      cycle and IOP pulse cycle.

PMID- 16792740
TI  - A simple new method for the construction of a ptosis crutch.
AB  - A technique by which a ptosis crutch can be fitted in minutes, using readily
      available and inexpensive materials and tools, is described. No specialist skills
      are needed and the device can be fitted to existing frames and lenses.

PMID- 16792741
TI  - Dynamic wettability of pHEMA-based hydrogel contact lenses.
AB  - Standard methods of contact angle analysis include sessile drop, captive bubble
      and Wilhelmy plate techniques; however, these methodologies are not particularly
      well suited for assessing the wettability of the surfaces of formed hydrogel
      contact lenses. This paper describes two methodologies that are adaptations of
      previously described techniques. The maximum adherent force method is an
      adaptation of the dynamic Wilhelmy plate technique that allows the assessment of
      whole, finished contact lenses. The dynamic photographic method allows the
      simultaneous assessment of the front and back surfaces of strip samples for the
      assessment of advancing and receding contact angles. Lenses investigated were
      made from polyhydroxyethyl methacrylate, hydroxyethyl methacrylate/methacrylic
      acid and hydroxyethyl methacrylate/glycerol methacrylate. The lenses were
      manufactured by lathing, spin-casting or cast-moulding techniques. Overall, both
      techniques demonstrated few differences between the wettability of different lens
      materials and no differences between materials of the 'same' lens type but
      manufactured by different methods. These findings are consistent with the results
      of clinical studies, which have shown little difference between contact lens
      surface wettability in vivo, which may be due to the apparent natural surface
      wettability-enhancing properties of the pre-lens tear film.

PMID- 16792742
TI  - Dynamics of ocular surface topography in healthy subjects.
AB  - Our topography system is an enhancement of a standard TMS-1 corneal topograph
      instrument (Computed Anatomy Inc., New York, NY, USA). Topographic images are
      captured at a rate of 4 s(-1), allowing the recording of a series of 120 images
      in 30 s after a complete blink. In this prospective preliminary study 15 healthy
      volunteers were examined. The main outcome measures were the time profile of
      changes in surface regularity index (SRI), surface asymmetry index (SAI) and
      simulated keratometry values (K1, K2). After a blink there was a tendency for
      improvement in ocular surface regularity. Later trends were less clear. Our
      topography system makes possible the detailed evaluation of tear-film dynamics in
      the post-blink period. The new technique may play an important role in the
      diagnosis of various tear-film abnormalities; the results may also have
      significant implications in the planning of refractive surgeries.

PMID- 16792743
TI  - Converting principal meridional representation of power to the coordinates of the
      power matrix using the matrix similarity transform.
AB  - General or local variations of the refractive elements in the eye, called
      irregular astigmatism, may manifest as non-orthogonal meridians when each
      principal meridian on the front surface of a cornea is independently aligned with
      the focussed mires of a keratometer. These are examples of astigmatic systems
      that are thick. The representation of power along the principal meridians is not
      suitable for quantitative work. The purpose of this research note is to convert
      power along principal meridians that can be non-orthogonal, to the coordinates of
      the power matrix that are suitable for quantitative analysis.

PMID- 16792744
TI  - The Scotopic Sensitivity Tester-1 and the detection of early age-related macular
      degeneration.
AB  - PURPOSE: Previous research shows that dark adaptation is a marker of early age
      related macular degeneration (ARMD), even when visual acuity remains good. This
      study evaluates whether a commercially available, off-the-shelf device for
      measuring dark adaptation, the Scotopic Sensitivity Tester-1 (SST-1), which uses
      a full-field stimulus, detects early ARMD as defined by fundus appearance. Fundus
      appearance is the gold standard method for defining the presence of ARMD.
      METHODS: Dark adaptation was measured using the SST-1 in 12 young adults (mean
      age 23 years), 17 old adults with normal retinal health (mean age 69) and 19 old
      adults with early ARMD (mean age 74). Normal retinal health and presence of early
      ARMD were defined by masked grading of dilated fundus photographs using the
      Wisconsin Age-Related Maculopathy Grading System. RESULTS: Older adults in normal
      retinal health exhibited slower dark adaptation as compared with young adults. No
      difference in the rate of dark adaptation was found between early ARMD patients
      and older adults in normal retinal health. CONCLUSIONS: Although the SST-1
      differentiated between young and older adults, it failed to detect dark
      adaptation abnormalities in early ARMD when referenced against older adults in
      normal retinal health. This may be attributable to the full-field stimulation
      used by the SST-1, which may be better suited for characterizing retinal
      degenerations affecting large retinal areas than for focal macular diseases like
      ARMD.

PMID- 16792745
TI  - Melanoma risk in congenital melanocytic naevi: a systematic review.
AB  - BACKGROUND: The risk of malignant melanoma in congenital melanocytic naevi (CMN)
      is a matter of controversial and ongoing debate. OBJECTIVES: The purpose of this
      systematic review is to provide a careful and detailed summary of the published
      data, including several recently published studies. METHODS: Articles on CMN
      (n=1424) were retrieved from Medline, 1966-October 2005. Case reports and studies
      lacking relevant clinical information were excluded. Only systematic collections
      of cases were taken into consideration. Series with fewer than 20 patients or
      studies with a mean follow-up of <3 years were regarded as epidemiologically less
      significant. RESULTS: Fourteen articles were finally chosen for further analysis.
      The studies varied significantly with respect to study design (source of cases;
      retrospective vs. prospective analysis), age of patients, follow-up time, and
      naevus characteristics. The frequency of melanomas ranged between 0.05% and 10.7%
      and was significantly higher in smaller studies (P<0.0001). In a total of 6571
      patients with CMN who were followed for a mean of 3.4-23.7 years, 46 patients
      (0.7%) developed 49 melanomas. The mean age at diagnosis of melanoma was 15.5
      years (median 7). By comparison with age-adjusted data from the Surveillance,
      Epidemiology and End Results database, we calculated that patients with CMN carry
      an approximately 465-fold increased relative risk of developing melanoma during
      childhood and adolescence. Primary melanomas arose inside the naevi in 33 of 49
      cases (67%). In seven cases (14%), metastatic melanoma with unknown primary was
      encountered; in four cases (8%) the melanoma developed at an extracutaneous site.
      The risk of developing melanoma and the rate of fatal courses were by far highest
      in CMN>or=40 cm in diameter. CONCLUSIONS: The overall risk of melanoma of 0.7% in
      all 14 studies was lower than expected. The higher incidence of melanomas in
      smaller studies indicates selection bias. The melanoma risk strongly depends on
      the size of CMN and is highest in those naevi traditionally designated as garment
      naevi. The median age of 7 years at diagnosis of melanoma points to a risk
      maximum in childhood and adolescence. Future studies on CMN should report: (i)
      diameter, percentage of body surface, and localization of the CMN; (ii)
      percentage of naevus area removed by excision or subject to dermabrasion or other
      superficial treatments; (iii) mean and median age at entry into the study; (iv)
      mean and median follow-up time; (v) details on each melanoma case; (vi)
      standardized morbidity ratio of melanoma; and (vii) percentage of neurocutaneous
      melanosis.

PMID- 16792747
TI  - Who benefits from calling a solar keratosis a squamous cell carcinoma?

PMID- 16792746
TI  - Solar (actinic) keratosis is squamous cell carcinoma.

PMID- 16792748
TI  - Topical suplatast tosilate (IPD) ameliorates Th2 cytokine-mediated dermatitis in
      caspase-1 transgenic mice by downregulating interleukin-4 and interleukin-5.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease
      characterized by elevated serum levels of IgE. AD is associated with Th2
      cytokines including interleukin (IL)-4, IL-5, IL-13 and IL-10. Systemic
      administration of suplatast tosilate (IPD) is currently used to treat Th2
      cytokine-mediated AD. OBJECTIVES: To evaluate the effect of topical IPD on skin
      lesions of AD using a genetically engineered AD mouse model (K14/caspase-1
      transgenic mouse: KCASP1Tg). METHODS: IPD ointment (3%) and white petrolatum (WP)
      were applied to KCASP1Tg mice every other day from 6 to 14 weeks after birth.
      Histopathological analysis of skin lesions and measurement of mRNA expression of
      cytokines in skin lesions and spleen cells were carried out. We also compared
      changes in serum parameters between IPD-treated and WP-treated KCASP1Tg mice.
      RESULTS: WP-treated mice developed dermatitis at 8 weeks after birth. However,
      skin lesions in IPD-treated mice were limited. Histopathologically, skin lesions
      in WP-treated KCASP1Tg mice showed marked inflammatory changes with increased
      mast cell infiltration. However, mice treated with IPD showed minimum skin
      lesions with scarce mast cell infiltration. WP-treated KCASP1Tg mice had
      significant elevation in the serum levels of histamine, IgE and IL-18 as compared
      with IPD-treated KCASP1Tg mice. mRNA expression of IL-4 and IL-5 in the skin
      lesions from WP-treated KCASP1Tg mice was significantly higher than in those from
      IPD-treated mice. In the spleen, the expression of IL-4, IL-5 and interferon
      gamma was significantly increased in WP-treated KCASP1Tg mice as compared with
      their IPD-treated counterparts. CONCLUSIONS: This study shows that topical
      therapy with IPD inhibits the expression of IL-4 and IL-5 and ameliorates skin
      manifestations in an AD mouse model, suggesting the potential usefulness of
      topical IPD for the treatment of AD.

PMID- 16792749
TI  - Inhibitory effects of Rumex japonicus Houtt. on the development of atopic
      dermatitis-like skin lesions in NC/Nga mice.
AB  - BACKGROUND: Rumex japonicus Houtt. (RJH) is one of the herbs used in Eastern
      countries for the treatment of atopic dermatitis (AD). It has been shown to have
      an antioxidative effect in human skin disease. OBJECTIVES: To examine whether RJH
      extract (RJH-E) suppresses the development of AD-like skin lesions in NC/Nga
      mice, which are induced by the repeated application of picryl chloride (PC).
      METHODS: The efficacy of RJH-E in NC/Nga mice was assessed by measuring symptom
      severity, scratching behaviour, Staphylococcus aureus numbers on an ear, and
      serum levels of IgE, interleukin (IL)-4 and interferon (IFN)-gamma. RESULTS: Oral
      administration of RJH-E to NC/Nga mice treated with PC inhibited the development
      of AD-like skin lesions as exemplified by a significant decrease in total skin
      symptom severity scores, and a decrease in hypertrophy, hyperkeratosis and
      infiltration of inflammatory cells in the skin. The scratching behaviour and
      numbers of S. aureus, which are known to be exacerbated in AD, were also
      significantly reduced by RJH-E. No significant change was observed in the serum
      levels of IFN-gamma, whereas IgE and IL-4 levels were significantly reduced by
      RJH-E. CONCLUSIONS: These results suggest that RJH-E inhibits the development of
      AD-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response.
      Our results indicate that RJH treatment could provide an effective alternative
      therapy for the management of AD.

PMID- 16792750
TI  - Oral zinc sulphate causes murine hair hypopigmentation and is a potent inhibitor
      of eumelanogenesis in vivo.
AB  - BACKGROUND: C57BL/6 a/a mice have been widely used to study melanogenesis,
      including in electron paramagnetic resonance (EPR) studies. Zinc cations modulate
      melanogenesis, but the net effect of Zn2+ in vivo is unclear, as the reported
      effects of Zn2+ on melanogenesis are ambiguous: zinc inhibits tyrosinase and
      glutathione reductase in vitro, but also enhances the activity of dopachrome
      tautomerase (tyrosinase-related protein-2) and has agonistic effects on
      melanocortin receptor signalling. OBJECTIVES: To determine in a C57BL/6 a/a
      murine pilot study whether excess zinc ions inhibit, enhance or in any other way
      alter hair follicle melanogenesis in vivo, and to test the usefulness of EPR for
      this study. METHODS: ZnSO(4).7H2O was continuously administered orally to C57BL/6
      a/a mice during spontaneous and depilation-induced hair follicle cycling (20 mg
      mL-1; in drinking water; mean+/-SD daily dose 1.2+/-0.53 mL), and hair
      pigmentation was examined macroscopically, by routine histology and by EPR.
      RESULTS: Oral zinc cations induced a bright brown lightening of new hair shafts
      produced during anagen, but without inducing an EPR-detectable switch from
      eumelanogenesis to phaeomelanogenesis. The total content of melanin in the skin
      and hair shafts during the subsequent telogen phase, i.e. after completion of a
      full hair cycle, was significantly reduced in Zn-treated mice (P=0.0005).
      Compared with controls, melanin granules in precortical hair matrix
      keratinocytes, hair bulb melanocytes and hair shafts of zinc-treated animals were
      reduced and poorly pigmented. Over the course of several hair cycles, lasting
      hair shaft depigmentation was seen during long-term exposure to high-dose oral
      Zn2+. CONCLUSIONS: High-dose oral Zn2+ is a potent downregulator of eumelanin
      content in murine hair shafts in vivo. The C57BL/6 mouse model offers an
      excellent tool for further dissecting the as yet unclear underlying molecular
      basis of this phenomenon, while EPR technology is well suited for the rapid,
      qualitative and quantitative monitoring of hair pigmentation changes.

PMID- 16792751
TI  - Sensitive and rapid diagnosis of human parvovirus B19 infection by loop-mediated
      isothermal amplification.
AB  - BACKGROUND: Human parvovirus B19 (B19) infections exhibit various skin
      manifestations that are similar to and hence hard to distinguish from many other
      skin diseases. The virological diagnosis of B19 infection is usually based on
      time-consuming serological tests and polymerase chain reaction (PCR). OBJECTIVES:
      In this study, a DNA amplification method, loop-mediated isothermal amplification
      (LAMP), was used for the diagnosis of B19 infection and was compared with PCR.
      METHODS: Ten patients with acute B19 infection and 16 patients with other skin
      diseases were enrolled. Sera and pharyngeal swabs were used directly as the
      templates in LAMP. The LAMP reaction was carried out at 63 degrees C for 1 h in a
      heat block. The reaction products were judged visually, by adding SYBR Green I
      into the tubes, and by gel electrophoresis. RESULTS: B19 DNA was detected by LAMP
      in 10 sera and all of seven tested pharyngeal swabs of 10 patients with acute B19
      infection but not in samples from 16 patients with other skin diseases. The
      results were in agreement with those obtained by PCR except for one case. The
      reason for the single discrepancy may be that the sensitivity of LAMP is 10(2)
      times higher than PCR. CONCLUSIONS: Detection of B19 DNA by LAMP in serum and
      especially in the pharynx is a rapid and convenient method for the diagnosis of
      acute B19 infection.

PMID- 16792752
TI  - Instrument-, age- and site-dependent variations of dermoscopic patterns of
      congenital melanocytic naevi: a multicentre study.
AB  - BACKGROUND: Recently, we identified and described dermoscopic aspects, present
      with a higher frequency in congenital melanocytic lesions with respect to
      acquired naevi. We also classified small- and medium-sized congenital naevi (CN)
      into nine subtypes according to their macroscopic and dermoscopic aspects.
      OBJECTIVES: Because the recognition of dermoscopic features may be instrument
      dependent, in this study, we wanted to check whether dermoscopic patterns
      specific for CN can be identified in digital images acquired by means of
      different instruments. We also wanted to check the validity of our previously
      proposed classification and assess possible age- and site-dependent variations of
      dermoscopic patterns and naevus subtypes. PATIENTS/METHODS: Images corresponding
      to 384 small- or medium-sized CN were collected in eight different centres
      employing four different instruments. Lesion images were evaluated and checked
      for the presence of specific dermoscopic criteria, classified, and compared with
      a database of 350 acquired naevi. RESULTS: Specific and unspecific dermoscopic
      features were identifiable in images acquired by means of all four instrument
      types. The mean number of identified features per lesion did not vary according
      to the instrument employed for the acquisition of the images; however, it was
      lower for lesions recorded employing low magnifications. The previously proposed
      classification was easily applied to the whole image database. The variegated
      naevus type was identified as a highly specific clinical/dermoscopic pattern.
      Dermoscopic features varied according to age and location. The globular type
      prevailed in subjects under 11 years of age and on the trunk, whereas the
      majority of reticular lesions were located on the limbs. CONCLUSIONS: Because
      definite clinical and histological criteria for the diagnosis of the congenital
      nature of naevi are lacking, the use of dermoscopy can be of great help in
      identifying those lesions where the presence of specific dermoscopic features
      makes the diagnosis of CN more likely. Moreover, dermoscopy can be useful both
      for the classification of lesions already identified as congenital according to
      definite clinical and anamnestic data and for a possible correlation of naevus
      phenotype and dermoscopic patterns to the risk of developing a malignant melanoma
      in prospective studies.

PMID- 16792753
TI  - Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease
      activity and abnormal differentiation of keratinocytes in psoriasis.
AB  - BACKGROUND: The expression of calcium-binding S100 molecules organized within the
      epidermal differentiation complex on chromosome 1q21 is disturbed in
      hyperproliferative skin diseases such as psoriasis. OBJECTIVES: We studied
      whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in
      psoriasis, correlated their amounts with disease activity and identified
      potential cellular sources. METHODS: Serum obtained from psoriasis patients or
      from healthy individuals was studied for S100A8 and S100A9 levels by enzyme
      linked immunosorbent assay. Data were correlated to disease activity as reflected
      by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and
      S100A9 were identified by in situ hybridization and immunohistochemistry of
      lesional psoriatic and nonlesional, nonpsoriatic skin. RESULTS: A significant
      increase of S100A8/S100A9 serum levels was found in patients with psoriasis
      compared with healthy controls. Grading the patients into two groups of severity,
      individuals with a PASI of <15 showed serum levels of 705+/-120 ng mL-1 (mean+/
      SEM, n=18), those with a PASI of >or=15 showed levels of 1315+/-150 ng mL-1
      (n=32) while controls presented with 365+/-50 ng mL-1. Performing in situ
      hybridization of lesional psoriatic skin we detected a dramatic induction of both
      S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the
      epidermis while expression was negligible in nonlesional, nonpsoriatic
      interfollicular epidermis. CONCLUSIONS: Our data demonstrate that
      hyperproliferation and abnormal differentiation of psoriatic skin is associated
      with a massive upregulation and secretion of S100A8 and S100A9, suggesting not
      only a prominent role of these molecules during intracellular calcium-dependent
      signalling but also implying distinct extracellular functions.

PMID- 16792754
TI  - Significant correlation between the CD63 assay and the histamine release assay in
      chronic urticaria.
AB  - BACKGROUND: Antibodies directed to the alpha subunit of the high affinity IgE
      receptor and the IgE molecule are proposed to be of pathogenetic relevance in a
      group of patients with chronic urticaria (CU). The diagnosis of autoimmune
      chronic urticaria (ACU) is difficult; the autologous serum skin test (ASST) seems
      to be a useful screening test, but reliable, additional confirmatory methods are
      needed. OBJECTIVES: To assess the diagnostic value of a modified serum-induced
      basophil activation test, the CD63 expression assay, in the diagnosis of ACU by
      comparing the results of the CD63 assay with the results of the histamine release
      (HR) test, the ASST and serum levels of soluble CD40 ligand (sCD40L). METHODS:
      Using basophils from an atopic (DA) and a nonatopic (DNA) donor the activity of
      sera of 72 patients with CU were measured in HR assay by enzyme-linked
      immunosorbent assay and in CD63 expression assay by flow cytometry. An ASST was
      carried out in all patients; in 30 of the 72 patients sCD40L was detected and
      correlations were derived between the different assays. Sera of 20 normal
      controls and 26 patients with systemic autoimmune diseases were also tested in
      the HR assay and in the CD63 expression assay. RESULTS: Histamine-releasing
      activity was detected in the sera of 51% (DA) and 32% (DNA) of CU patients and
      57% (DA) and 28% (DNA) of sera upregulated CD63 expression on the surface of
      basophils from the different donors. There was a significant correlation between
      the HR and the CD63 assays carried out on both donors, but the ASST showed a
      strong correlation with the HR assay only for basophils from the DA. The serum
      level of sCD40L was significantly higher in patients with CU compared with
      controls, but the difference between the autoimmune and the nonautoimmune groups
      was not significant. CONCLUSIONS: The CD63 expression assay seems to be a
      reliable functional test in the diagnosis of ACU, particularly if highly
      sensitive donor basophils are used, but the determination of the sCD40L serum
      level was not sufficient to differentiate between the autoimmune and the
      nonautoimmune patient groups.

PMID- 16792755
TI  - Concomitant traumas influence prognosis in melanomas of the nail apparatus.
AB  - BACKGROUND: In nail apparatus melanomas (NAM), the role of standard melanoma
      prognostic factors is under discussion. The prognostic influence of traumas to
      the clinically apparent tumour has not been sufficiently examined. OBJECTIVES: To
      estimate the influence of traumas against the background of standard prognostic
      factors on the course of NAM. METHODS: In 33 patients (20 women, 13 men, median
      age 65.0 years) with NAM (median tumour thickness 3.5 mm), we retrospectively
      examined a detailed history of trauma to the affected extremity at first
      presentation. Histological or other standard prognostic factors and follow-up
      were studied prospectively using a standardized protocol. RESULTS: Of 33
      patients, 21 had suffered injury to the clinically apparent melanoma primary
      between 4 and 72 months prior to definitive surgical treatment (diagnostic biopsy
      up to 3 months ahead of excision of the melanoma was not considered). Eight of
      these patients had undergone inadequate therapy procedures. In Kaplan-Meier
      analysis, trauma to the clinically apparent tumour and tumour thickness were
      found to be significant prognostic factors for recurrence-free survival, and
      trauma to the clinically apparent tumour, Clark level and tumour thickness were
      significant prognosis predictors for overall survival. In Cox's proportional
      hazards model, trauma to the clinically apparent tumour was found to be a
      significant and independent risk factor with regard to overall survival (hazard
      ratio 5.39; P = 0.029). An influence of trauma on the primary pathogenesis of NAM
      could not be confirmed. Only three patients reported trauma prior to the onset of
      tumour. CONCLUSIONS: From our data, trauma to the clinically apparent tumour
      might be a considerable risk factor in NAM. The diagnosis of NAM should be
      considered in lesions of the nail apparatus and further deterioration of the
      prognosis due to inadequate therapeutic attempts or injury to the NAM should be
      avoided.

PMID- 16792756
TI  - A novel mutation in the XPA gene associated with unusually mild clinical features
      in a patient who developed a spindle cell melanoma.
AB  - BACKGROUND: Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in
      most cases, defective nucleotide excision repair (NER) of ultraviolet radiation
      (UV)- and chemical-induced DNA damage. The condition is characterized by an
      increased sensitivity of the skin to UV radiation, with early development of
      pigmentary changes and premalignant lesions in sun-exposed areas of the skin,
      signs of photoageing and a greatly increased incidence from a young age of skin
      tumours including melanoma. Approximately 20% of patients with XP show
      neurological abnormalities of varying severity due to primary neuronal
      degeneration. Genetic analysis by somatic cell hybridization has led to the
      identification in the NER-defective form of XP of seven complementation groups,
      designated XP-A to XP-G. These complementation groups correspond to different
      proteins involved in the NER process. XP-A classically includes some of the most
      severely affected patients. OBJECTIVES: We describe a 61-year-old Punjabi woman
      with XP. Remarkably she had only mild cutaneous abnormalities, minimal
      neurological features and unusual longevity, and developed a malignant spindle
      cell melanoma. There are few previous reports of spindle cell melanoma associated
      with XP. To gain insight into the aetiology of these unusual features, we sought
      to analyse the DNA repair properties of the patient and identify the
      complementation group and the causative mutation in the defective gene. METHODS:
      Unscheduled DNA synthesis and the inhibition of RNA synthesis were measured. The
      complementation group was assigned by fusing the cells of our patient with XP
      cells of known complementation groups and determining the ability to carry out
      unscheduled DNA repair. Molecular analysis of the cDNA was carried out by
      polymerase chain reaction and DNA sequencing. RESULTS: Levels of DNA repair were
      extremely low and complementation analysis assigned the defect to the XP-A group.
      Sequencing of the XPA gene revealed a novel homozygous mutation of A-->G at the
      eighth nucleotide of intron 4 causing aberrant splicing and a nonfunctional
      truncated XP-A protein. However, a small amount of normally spliced mRNA was
      detected at <5% the level in normal cells. CONCLUSIONS: The small amount of
      normally spliced mRNA detected may be sufficient to explain the relatively mild
      clinical features in our patient.

PMID- 16792757
TI  - Pseudoxanthoma elasticum: evaluation of diagnostic criteria based on molecular
      data.
AB  - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a genetic disorder due to mutations
      in the gene encoding the transmembrane transporter protein adenosine triphosphate
      binding cassette (ABC)-C6, resulting in calcification of elastic fibres in the
      skin, eyes and cardiovascular system. OBJECTIVES: To evaluate the diagnostic
      criteria for PXE based on molecular data. METHODS: Of 10 families with a positive
      history of PXE 142 subjects were investigated for clinical symptoms, histological
      findings and genetic haplotype analysis. RESULTS: Of these, 25 subjects were
      haplotypic homozygous for PXE and 23 had typical clinical and histopathological
      manifestations. Two of the 25 patients showed such marked solar elastosis and
      macular degeneration that PXE could not be confirmed clinically. Sixty-seven
      subjects were haplotypic heterozygous carriers and 50 were haplotypic homozygous
      unaffected. Of these 117 subjects, 116 showed no cutaneous or ophthalmological
      signs of PXE. In one of the 50 haplotypic homozygous unaffected patients
      important solar elastosis and scarring of the retina mimicked PXE lesions. Only
      four of the 67 haplotypic heterozygous carriers had biopsies of nonlesional skin;
      all were histopathologically normal. CONCLUSIONS: In our patients, PXE presents
      as an autosomal recessive genodermatosis. Correlation of haplotype and phenotype
      confirmed actual major diagnostic criteria. In patients with marked solar
      elastosis and/or severe macular degeneration clinical diagnosis can be impossible
      and molecular testing is needed to confirm the presence of PXE. To the best of
      our knowledge our large study compares for the first time clinical findings with
      molecular data.

PMID- 16792758
TI  - Mutation of the tumour suppressor p33ING1b is rare in melanoma.
AB  - BACKGROUND: The p33ING1b gene is involved in the p53-dependent response to DNA
      damage following exposure to ultraviolet radiation, and has recently been
      reported to be mutated in 20% of melanoma tumours. OBJECTIVES: We sought to
      assess the p33ING1b mutation rate in our large panels of fresh melanomas and
      melanoma cell lines. METHODS: We screened 83 primary melanomas and 55 melanoma
      cell lines for mutations in p33ING1b by single-strand conformational polymorphism
      analysis and by direct sequencing. RESULTS: In contrast to previous reports, we
      found no somatic p33ING1b mutations in our panel of melanomas. We found that some
      of the discrepancy between our results and previously published studies may be
      due to inadvertent amplification of the ING1 pseudogene (INGX), and/or
      contamination of some samples with murine Ing1. CONCLUSIONS: p33ING1b mutations
      in melanoma are rare. We have highlighted the importance of allele-specific
      primer design to avoid pseudogene amplification, and also the necessity to
      confirm the genetic identity and species of origin of individual cell lines.
      Further studies are needed to clarify the possible role of p33ING1b in melanoma
      tumorigenesis.

PMID- 16792759
TI  - The management of skin malignancy: to what extent should we rely on clinical
      diagnosis?
AB  - BACKGROUND: Cutaneous malignancy forms a major part of the dermatologist's
      workload. Clinical diagnosis is an important factor in facilitating the urgent
      excision of squamous cell carcinomas (SCC) and malignant melanomas. OBJECTIVES:
      To identify the numbers and types of malignant skin tumours managed in an NHS
      teaching hospital and to assess the diagnostic accuracy. METHODS: Data were
      collected on every histologically proven malignant skin lesion over a 6-month
      period. RESULTS: One thousand one hundred and ninety-five malignant skin tumours
      were identified: 78% were basal cell carcinomas, 14% were SCC, 6% were malignant
      melanomas and the remaining 2% included Merkel cell tumours, malignant adnexal
      tumours and lentigo maligna. Eighty-one per cent of the tumours were managed by
      dermatologists. The correct clinical diagnosis had been made by the secondary
      care clinician in 84% of cases but an incorrect clinical diagnosis was given in
      32% of SCC. Of the 1195 tumours, 916 (77%) had a primary excision and 92% (843 of
      916) of these were completely excised. CONCLUSIONS: The majority of skin
      malignancies (968 of 1195, 81%) were managed by dermatologists. Where primary
      excision was attempted, this was complete in 91% (767 of 916) of cases. The
      correct clinical diagnosis was made in 84% of all tumours, but 32% of SCC were
      not correctly diagnosed prior to surgery.

PMID- 16792760
TI  - Percutaneous penetration of sodium lauryl sulphate is increased in uninvolved
      skin of patients with atopic dermatitis compared with control subjects.
AB  - BACKGROUND: Involved regions of the skin in patients with atopic dermatitis (AD)
      have been shown to have higher transepidermal water loss (TEWL), indicating a
      compromised skin barrier. Whether uninvolved skin also has diminished barrier
      characteristics is controversial. OBJECTIVES: To study the penetration of sodium
      lauryl sulphate (SLS) into uninvolved skin of patients with AD compared with the
      skin of control subjects. METHODS: Percutaneous penetration was assessed using
      the tape stripping technique on the stratum corneum (SC). Twenty patients with AD
      and 20 healthy subjects were exposed to 1% SLS for 4 h on the mid-volar forearm.
      After the end of exposure the SC was removed by adhesive tape. The amount of SLS
      was determined in each consecutive strip. Fick's second law of diffusion was used
      to deduce the diffusivity and the partition coefficient of SLS between water and
      the SC. RESULTS: The SC thickness was similar in both groups; however, the TEWL
      was higher in patients with AD compared with that of the control group (mean+/-SD
      8.4+/-4.3 and 6.3+/-2.0 g m-2 h-1, respectively). There was a correlation between
      SC thickness and TEWL in control subjects but no correlation was found in
      patients with AD. The diffusivity of SLS through uninvolved AD skin was higher
      compared with normal skin (mean+/-SD 12.7+/-5.8x10(-9) and 6.2+/-3.0x10(-9) cm-2
      h-1, respectively), while the partition coefficient between SC and water was
      lower (mean+/-SD 137+/-64 and 196+/-107, respectively). CONCLUSIONS: The results
      show a different penetration profile of SLS into the SC of patients with AD
      compared with control subjects. This indicates that even noninvolved skin in
      patients with AD has altered barrier characteristics, emphasizing the importance
      of skin protection and prevention of skin contact with chemicals.

PMID- 16792761
TI  - Efficacy of the pulsed dye laser in the treatment of localized recalcitrant
      plaque psoriasis: a comparative study.
AB  - BACKGROUND: Localized chronic plaque psoriasis, resistant to local therapy, may
      be very hard to treat. The treatment of these lesions with a pulsed dye laser
      (PDL) has been described before, but a comparative study between the PDL and a
      potent topical treatment has never been performed. OBJECTIVES: To compare the
      efficacy of the PDL in the treatment of localized, recalcitrant plaque psoriasis
      with a potent topical therapy, using calcipotriol/betamethasone dipropionate
      (Dovobet) as an active comparator. METHODS: Eight patients with psoriasis were
      treated with both PDL (585 nm) and calcipotriol/betamethasone dipropionate in an
      open, intrapatient, left-right comparison. A plaque severity score (sum score)
      and photographs were used to document the course of therapy. Patients reported
      pain on a visual analogue scale. RESULTS: Both treatments were well tolerated,
      although one patient left the study due to post-PDL treatment pain. A significant
      difference in the sum score 12 weeks after treatment was seen in favour of the
      PDL (62% vs. 19% reduction; P<0.05). Scores for erythema declined significantly
      at week 12 in both the PDL and the calcipotriol/betamethasone dipropionate group
      (P<0.001). Induration and desquamation scores were significantly reduced at week
      12 in the PDL group, without a statistically significant reduction in
      calcipotriol/betamethasone-treated lesions. The pain scores declined with
      progressive PDL treatments, although not statistically significantly.
      CONCLUSIONS: PDL treatment might be considered for the treatment of localized,
      recalcitrant plaque psoriasis, when other topical therapies have failed.

PMID- 16792762
TI  - Selective sweat gland removal with minimal skin excision in the treatment of
      axillary hyperhidrosis: a retrospective clinical and histological review of 15
      patients.
AB  - BACKGROUND: Limited axillary skin excision and selective sweat gland removal from
      adjacent skin (Shelley's procedure) is currently rarely used for hyperhidrosis.
      OBJECTIVES: To determine whether this technique is a good way of permanently
      reducing axillary sweating. METHODS: This was a prospective, open, nonrandomized
      trial of the therapy, conducted in a university dermatology department. A small
      skin ellipse, parallel to the skin crease lines, was excised from the centre of
      the area of maximal sweating. The wound edges were undermined to the extent of
      maximal sweating and the skin reflected. Large visible sweat glands attached to
      the undersurface of the adjacent skin could be readily identified and were
      snipped off using scissors. We treated 15 axillae in eight patients with axillary
      hyperhidrosis. Sweat reduction was assessed by the patients who estimated the
      percentage reduction in sweating postoperatively. The scar appearance was graded
      by the surgeon. Haematoxylin and eosin-stained transverse sections of eight
      axillary skin ellipses from five subjects were examined histologically to
      establish the size, position and depth of the sweat gland tissue. RESULTS: All of
      the patients responded to treatment: mean sweat reduction was 65% (range 40-90%).
      Mean follow up was 1.3 years (range 0.1-6) and sweat reduction was maintained
      over this period. Histological material was available from five patients: sweat
      glands lay slightly deeper than hair follicles; glandular tissue occupied an
      average thickness of 3.5 mm in the 5-mm thick piece of skin. Apocrine gland
      lobules were more numerous and larger than eccrine gland lobules. Both gland
      types were in close apposition and did not occupy distinctly different depths
      within the skin. CONCLUSIONS: Local surgery using limited axillary skin excision
      and selective sweat gland removal remains one of the safest ways of permanently
      reducing axillary sweating.

PMID- 16792763
TI  - Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in
      senile lentigo and ageing skin.
AB  - BACKGROUND: Senile lentigo (SL) is a pigmentation disorder that occurs
      predominantly on the dorsa of the hands, the forearms and the face; its incidence
      increases with age. Histological hallmarks of SL lesions are hyperpigmentation of
      the epidermis and elongation of the epidermal rete ridges. Various factors such
      as alpha-melanocyte-stimulating hormone, endothelin-1 or stem cell factor are
      involved in the onset and maintenance of the increased pigmentation. Alterations
      of the dermal compartment have not yet been analysed in detail in SL. OBJECTIVES:
      To study the occurrence and distribution of melanin in the dermis from SL and
      aged skin, biopsies from 12 subjects were morphologically analysed by light and
      electron microscopy in comparison with unaffected skin. METHODS: Punch biopsies
      of SL and adjacent skin from 12 male or female volunteers aged 52-81 years were
      prepared for light and electron microscopy and samples were analysed by
      morphological, morphometric, histochemical and immunohistochemical methods.
      RESULTS: The epidermis from SL revealed morphological features such as
      hyperpigmentation of basal keratinocytes and the formation of elongated rete
      ridges. S100+ melanocytes in the stratum basale were not markedly increased,
      indicating that the hyperpigmentation is predominantly due to changes in melanin
      synthesis, distribution or turnover. Quantification of epidermal cells expressing
      the proliferation marker Ki67 did not show an increase of this parameter in SL,
      indicating that at least in the established lesion cell proliferation is not
      enhanced. We further focused on the dermal compartment and observed granulated
      cells which were more abundant in SL. Electron microscopic and histochemical
      analysis revealed that the granulation of these cells is based on melanosomes,
      mostly present in large melanosomal complexes. Immunohistochemistry using
      antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be
      predominantly FXIIIa+ dermal dendrocytes, which were about six times more
      abundant than CD68+ macrophages. CONCLUSIONS: In SL an increased number of
      melanophages was found compared with unaffected skin from the same subject. These
      melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional
      consequences of the massive melanin uptake by dermal dendrocytes are discussed.

PMID- 16792764
TI  - E6/E7 expression of human papillomavirus types in cutaneous squamous cell
      dysplasia and carcinoma in immunosuppressed organ transplant recipients.
AB  - BACKGROUND: DNA of cutaneous human papillomavirus (HPV) types is frequently found
      in nonmelanoma skin cancer, and their E6 and E7 proteins can have transforming
      properties. OBJECTIVES: To assess the biological activity of HPV types found in
      tumour tissues we examined HPV E6/E7 RNA expression and the antibody response to
      E6, E7 and L1 proteins. METHODS: Thirty-one snap-frozen biopsies from six
      immunosuppressed organ transplant recipients representing seven squamous cell
      carcinomas (SCCs), one basal cell carcinoma, four actinic keratoses (AKs), seven
      normal skin and 12 verrucae vulgaris (Vv) were analysed for 24 cutaneous HPV
      types by an L1 DNA polymerase chain reaction (PCR)-based method. The presence of
      E6/E7 transcripts of HPV 5, 8, 9, 15 and 20 was investigated by real-time reverse
      transcription-PCR. HPV DNA load was determined for HPV 8, 9 and 15 in 11
      biopsies. Antibody response was measured by enzyme-linked immunosorbent assay
      using affinity-purified, bacterially expressed complete viral proteins fused to
      glutathione S-transferase as antigens. RESULTS: HPV DNA was detected in 25 of 31
      tissue samples, indicating eight single and 17 multiple HPV infections. E6/E7
      transcripts of HPV 8, 9 and 15 were found in low copy numbers in one SCC and
      three AKs, but not in normal skin or Vv. All four patients examined showed
      antibodies to cutaneous HPV antigens, but the antibody response did not correlate
      with E6/E7 expression detected in the tumour. CONCLUSIONS: Transcriptional
      activity of the E6/E7 oncogenes in AK and SCC suggests an active role of HPV in
      the lesion.

PMID- 16792765
TI  - Defining the dermatological content of the undergraduate medical curriculum: a
      modified Delphi study.
AB  - BACKGROUND: Dermatological problems are common, but in undergraduate medical
      courses time for learning dermatology and teaching dermatology is limited. The
      Delphi technique has been used in other specialties to define undergraduate and
      postgraduate curricula and to reach consensus on what is important. OBJECTIVES:
      To identify the core dermatological content of the undergraduate medical
      curriculum. METHODS: Modified Delphi technique. A questionnaire was designed
      after review of previous recommendations made by dermatologists. Items were
      written as explicit learning outcomes. A multidisciplinary panel of 66
      individuals responded. Outcomes were rated using a Likert scale (1-5). RESULTS:
      Fifty-three learning outcomes were rated 'very important'. We recommend that
      these are included in the content of U.K. undergraduate medical core curricula.
      CONCLUSIONS: A multidisciplinary panel identified dermatological learning
      outcomes that should be achieved by all medical graduates. Undergraduate medical
      curricula must provide sufficient resources for learning, teaching and assessment
      of dermatology so that graduates achieve these outcomes.

PMID- 16792766
TI  - A comparative study of impairment of quality of life in children with skin
      disease and children with other chronic childhood diseases.
AB  - BACKGROUND: Chronic disease can have physical and psychological effects which
      affect social functioning. These effects can be better understood from the
      perspective of parent and child by the use of health-related quality of life
      (HRQL) measures. Various HRQL measures are now available, of which generic health
      measures have been the most widely used. These permit comparison between
      different diseases and also the normal population. OBJECTIVES: To cross-validate
      a new generic HRQL proxy measure for children, the Children's Life Quality Index
      (CLQI), with an established speciality-specific dermatological questionnaire, the
      Children's Dermatology Life Quality Index (CDLQI), in a group of children with
      chronic skin diseases. The impairment of HRQL in the same group of children with
      skin disease was then compared with that associated with other common chronic
      childhood diseases using the CLQI. METHODS: The CDLQI was completed by 379
      children aged 5-16 years with skin disease of more than 6 months' duration. Their
      parents (n=379) and parents of 161 children aged 5-16 years with other chronic
      diseases were also asked to complete a proxy measure, the CLQI. RESULTS: Using
      linear regression analysis, the CLQI and the CDLQI scores showed a strong linear
      association (rs=0.72, P<0.001) and on a Bland-Altman plot, reasonably good
      agreement (expressing scores out of 100, the 95% limits of agreement were from 
      25.5/100 to 26.7/100). In the child's opinion psoriasis and atopic dermatitis
      (AD) caused the greatest impairment (CDLQI scores of 30.6% and 30.5%), followed
      by urticaria (20%) and acne (18%). Using the generic CLQI (scored 0-36), from the
      parental perspective the highest score was for AD (33%), followed by urticaria
      (28%), psoriasis (27%) and alopecia (19%). Comparing this with children with
      other chronic diseases, those with cerebral palsy had the highest score (38%),
      followed in descending order by those with generalized AD (33%), renal disease
      (33%), cystic fibrosis (32%), urticaria (28%), asthma (28%) and psoriasis (27%).
      Diseases such as epilepsy (24%) and enuresis (24%) scored higher than diabetes
      (19%), localized eczema (19%), alopecia (19%) and acne (16%). CONCLUSIONS: Using
      the CLQI we have shown that HRQL impairment in children with chronic skin disease
      is at least equal to that experienced by children with many other chronic
      diseases of childhood, with AD and psoriasis having the greatest impact on HRQL
      among chronic skin disorders and only cerebral palsy scoring higher than AD.
      Cross-validation of the CLQI with the CDLQI in the group of children with skin
      disease demonstrates a strong linear association and good agreement between the
      two.

PMID- 16792767
TI  - Tacrolimus ointment 0.1% in pityriasis alba: an open-label, randomized, placebo
      controlled study.
AB  - BACKGROUND: Pityriasis alba (PA) is a frequent reason for dermatological
      consultation because of its chronic course, tendency to relapse and aesthetic
      impact. OBJECTIVES: In view of its strong association with atopic dermatitis, the
      objective of this open-label study was to assess the efficacy and safety of
      tacrolimus ointment in the treatment of PA compared with the efficacy of
      moisturizers. PATIENTS/METHODS: The study population consisted of 60 individuals
      of phototype III or IV according to Fitzpatrick's classification, aged 6-21
      years. Patients were randomly assigned to one of two groups. Subjects in group A
      were instructed to apply tacrolimus ointment 0.1% twice daily, 12 h apart, on all
      hypopigmented macules. Standard moisturizers with SPF 20 sunscreen were used on
      all lesions applied at least 30 min apart from the tacrolimus ointment. Subjects
      in group B used solely the same moisturizers with sunscreen. Hypopigmented areas
      were evaluated at baseline and weeks 0, 3, 6 and 9 by investigators for scaling,
      hypopigmentation and pruritus on a scale of 0-3. Patient satisfaction was also
      recorded on a scale of 0-3. All adverse effects were recorded. RESULTS: A
      statistically significant improvement through time, in hypopigmentation, pruritus
      and scaling was observed in both groups during the course of 9 weeks.
      Hypopigmentation resolved from a baseline score of 2.38+/-0.64 to 1.15+/-0.54 at
      week 3, 0.46+/-0.51 at week 6 and 0.00+/-0.00 at week 9 for the group applying
      tacrolimus ointment 0.1%. The difference in improvement between the two groups
      was statistically significant on all three assessments for hypopigmentation
      (P<0.001), and for pruritus on week 6 and 9 assessments (P<0.05). Three patients
      (11.5%) in the tacrolimus group reported a mild transient sensation of burning.
      All patients in the tacrolimus group reported they were completely satisfied or
      just satisfied with the treatment compared with only 50% of patients using the
      placebo. CONCLUSIONS: Tacrolimus ointment 0.1% appears to be an effective and
      safe treatment for PA.

PMID- 16792768
TI  - Treatment of erythrodermic psoriasis with etanercept.
AB  - BACKGROUND: Severe variants of psoriasis, such as erythrodermic psoriasis, may be
      associated with serious morbidity and mortality. Current treatment options for
      erythrodermic psoriasis are limited, unsatisfactory and potentially associated
      with organ-specific toxicity. Recently, a new class of agents, targeted
      biological therapies, has emerged. Etanercept is a recombinant human fusion
      protein acting as a competitive inhibitor of tumour necrosis factor-alpha. The
      safety and efficacy of etanercept have been widely demonstrated in psoriatic
      arthritis and moderate to severe plaque-type psoriasis. OBJECTIVES: To assess the
      efficacy and tolerability of etanercept in the treatment of erythrodermic
      psoriasis over a period of 24 weeks. METHODS: Ten patients, eight men and two
      women, were selected to receive etanercept 25 mg subcutaneously twice weekly. The
      Psoriasis Area and Severity Index (PASI) score, ranging from 0 to 72, was used to
      assess the severity of disease. RESULTS: Etanercept was well tolerated and led to
      a significant reduction in the severity of disease over the period of treatment.
      After 24 weeks, the mean PASI score decreased from 39.1 (baseline) to 5.1. At
      week 12, five of 10 (50%) patients achieved an improvement of PASI score from
      baseline exceeding 75%. At week 24, six of 10 patients (60%) achieved or
      maintained an improvement of PASI score from baseline exceeding 75% while two
      patients (20%) maintained an improvement of between 50% and 75%. CONCLUSIONS: In
      this study, etanercept has been demonstrated to be an effective treatment for
      erythrodermic psoriasis, providing a safe and convenient alternative to current
      therapies.

PMID- 16792769
TI  - Infliximab for severe, treatment-resistant psoriasis: a prospective, open-label
      study.
AB  - BACKGROUND: Infliximab, a mouse-human chimeric monoclonal antibody directed
      against tumour necrosis factor-alpha, has been shown to be effective for moderate
      to severe psoriasis, but there are few data published on its use in recalcitrant,
      treatment-resistant disease or in combination with other antipsoriatic therapies.
      OBJECTIVES: To report our experience with infliximab in the treatment of patients
      attending a tertiary referral service with severe recalcitrant disease. METHODS:
      All patients attending a tertiary referral service for severe psoriasis who were
      treated with infliximab between 2002 and July 2005 were entered into a
      prospective, open-label study. Details on disease phenotype, clinical course and
      adverse events were recorded together with measures of disease severity
      [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index,
      clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals
      throughout the treatment period. RESULTS: Twenty-three patients were treated with
      infliximab during the study; one patient had pustular psoriasis and was therefore
      excluded from statistical analysis. All had severe disease (baseline PASI 26.5+/
      6.7, mean+/-SD, n=22) and had received at least two systemic therapies for
      psoriasis in the past; 16 were taking one or more concomitant therapies at the
      time of treatment initiation. At week 10, 95% had achieved a 50% or greater
      improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater
      improvement (PASI 75). Efficacy was sustained in the longer term, with eight of
      10 patients on treatment for more than 11 months maintaining at least a PASI 50.
      Only one patient had treatment withdrawn due to lack of efficacy, two suffered
      severe systemic infections including extrapulmonary tuberculosis (splenic
      abscess) and cellulitis, and six have discontinued due to adverse effects
      including infusion reactions (two), severe thrombocytopenia (one), hepatitis
      (one) and malignancy (two). CONCLUSIONS: Data from this open-label study suggest
      that infliximab is a rapidly effective treatment for patients with severe,
      treatment-resistant disease, although approximately 25% of patients had to
      discontinue therapy due to the development of serious adverse effects. Long-term
      follow-up, continued pharmacovigilance, and further controlled comparative
      studies will be required to evaluate fully the risks associated with infliximab
      in the context of this already difficult to treat population.

PMID- 16792770
TI  - CLinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in
      patients with moderate-to-severe plaque psoriasis: results from a phase III
      international randomized, placebo-controlled trial.
AB  - BACKGROUND: Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks
      multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis,
      including T-cell activation, migration to the skin, reactivation in psoriatic
      skin and interactions with keratinocytes. OBJECTIVES: This multinational,
      randomized, double-blind, placebo-controlled, parallel-group trial was designed
      to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once
      weekly for 12 weeks compared with placebo in a population that included high-need
      patients, defined as those for whom at least two systemic therapies were
      unsuitable because of lack of efficacy, intolerance or contraindication.
      PATIENTS/METHODS: Patients with moderate-to-severe plaque psoriasis [involvement
      of >or=10% of total body surface area and Psoriasis Area and Severity Index
      (PASI)>or=12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab
      or placebo. The primary efficacy endpoint was the proportion of patients
      achieving >or=75% PASI improvement (PASI-75 response) at week 12 in the intention
      to-treat population; secondary endpoints included changes in PASI, static
      Physician's Global Assessment, Physician's Global Assessment of change from
      baseline and percentage of body surface area affected. Results We enrolled 793
      patients (529 received efalizumab and 264 placebo), including 526 high-need
      patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were
      29.5% for efalizumab compared with 2.7% for placebo among high-need patients
      (P<0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full
      study population (P<0.0001). RESULTS: for all secondary efficacy endpoints showed
      superiority of efalizumab over placebo in both the high-need and the full
      populations. Efalizumab demonstrated a favourable safety profile, without
      evidence of systemic toxicity, in both the high-need group and the overall study
      population. CONCLUSIONS: The efficacy and safety of efalizumab therapy were
      comparable between high-need patients and the more general moderate-to-severe
      psoriasis patient population. In view of its demonstrated efficacy and safety
      profile, efalizumab represents a valuable option for the treatment of adult
      patients with moderate-to-severe plaque psoriasis, including high-need patients.

PMID- 16792771
TI  - An evaluation of the efficacy of topical application of salicylic acid for the
      treatment of familial cylindromatosis.
AB  - BACKGROUND: Familial cylindromatosis is a rare genetic disorder, giving rise to
      neoplasms of the skin appendages. We have recently shown that loss of the
      cylindromatosis tumour suppressor gene leads to activation of NF-kappaB, a
      transcription factor having antiapoptotic activity. This provides a possible
      explanation for the deregulated growth of cylindromas. In cell-based assays,
      salicylate can prevent NF-kappaB activation caused by loss of the cylindromatosis
      gene, suggesting that salicylic acid application might be a potential treatment
      for cylindromatosis. OBJECTIVES: To assess the effectiveness of topical
      application of salicylic acid on familial cylindromas. METHODS: Cylindromas in
      five patients from four different cylindromatosis families were treated with
      twice daily and then once daily topical salicylic acid. Clinical response was
      determined by serial tumour measurements. RESULTS: In total 17 cylindromas in
      five patients were studied: 12 target lesions and five control lesions. The
      median size of the cylindromas was 1.0 cm (range, 0.6-2.8 cm). Two of the 12
      cylindromas showed a complete remission. Another eight lesions showed some
      response, but not sufficient to qualify as partial remission. The control lesions
      remained stable or increased in size. CONCLUSIONS: Salicylic acid is a well
      tolerated and potential new treatment for cylindromatosis.

PMID- 16792772
TI  - Age-associated decrease of CD1d protein production in normal human skin.
AB  - BACKGROUND: CD1d belongs to a family of antigen-presenting molecules structurally
      related to the classical major histocompatibility complex class I proteins.
      OBJECTIVES: To examine the expression pattern of CD1d protein in normal human
      skin with ageing. METHODS: Twenty normal human skin biopsy specimens were
      obtained from 20 healthy individuals. The latter were divided into three age
      groups: children (5-20 years), adults (21-50 years) and the elderly (51-81
      years). The intensity of CD1d protein production was examined in human skin using
      immunofluorescent and immunoalkalinephosphatase staining methods. RESULTS: In the
      epidermis, CD1d protein production was strong in the skin of the children and
      declined gradually with age, being moderate in adults and weak in the elderly. As
      compared with values in children, there was a statistically significant decrease
      (P<0.05) in CD1d protein production in the elderly. In the dermis, CD1d protein
      production was strong in the fibroblasts, sweat glands, sebaceous glands, blood
      vessels and hair follicles regardless of age. CONCLUSIONS: Our study reports a
      decreased CD1d protein production in normal human skin with ageing. The clinical
      ramifications of these observations mandate further investigations.

PMID- 16792773
TI  - Sternal malformation/vascular dysplasia syndrome with linear hypopigmentation.
AB  - We report a 7-year-old boy who presented with a facial haemangioma, a
      circumscribed depression over the sternum, coarctation of the aorta, ventricular
      septal defect and dysplastic cerebral arteries responsible for an episode of
      acute infarct. This combination of clinical features has been described as the
      sternal malformation/vascular dysplasia syndrome or PHACES syndrome. At the age
      of 5 years, lines of hypopigmentation were noted on the right arm, the right hand
      and the back, along the lines of Blaschko, with no history of any preceding
      inflammatory changes, and have persisted unchanged. These pigmentary changes have
      not previously been reported in association with this syndrome.

PMID- 16792774
TI  - Cutaneous signs as a presenting manifestation of alcohol excess.
AB  - We describe three patients who presented with a total of four episodes of an
      inflammatory dermatosis associated with alcohol abuse. In each case, the rash had
      similar characteristic features. The patients responded promptly to emollients
      and topical steroids but not to zinc replacement therapy. Other nutrient
      deficiencies were not identified. In addition, long-term remission seemed to be
      dependent on a reduction in alcohol consumption. We postulate that this is a
      separate cutaneous manifestation of chronic alcohol misuse and that this syndrome
      may be more common than previously thought.

PMID- 16792776
TI  - Utilization of a cryptic noncanonical donor splice site in the KRT14 gene causes
      a mild form of epidermolysis bullosa simplex.

PMID- 16792775
TI  - A novel mutation in the 12(R)-lipoxygenase (ALOX12B) gene underlies nonbullous
      congenital ichthyosiform erythroderma.

PMID- 16792777
TI  - A novel ABCA12 mutation underlying a case of Harlequin ichthyosis.

PMID- 16792778
TI  - Compound blue naevus: a potential simulator of melanoma.

PMID- 16792779
TI  - Giant pilomatricoma associated with hypercalcaemia and elevated levels of
      parathyroid hormone-related protein.

PMID- 16792780
TI  - Treatment of plaque psoriasis by sequential therapy with two 'biologics': the
      'hit and run' approach, a report of two cases.

PMID- 16792781
TI  - Improvement of psoriasis and cutaneous side-effects during tyrosine kinase
      inhibitor therapy for renal metastatic adenocarcinoma. A role for epidermal
      growth factor receptor (EGFR) inhibitors in psoriasis?

PMID- 16792782
TI  - A 2005 survey of clinical academic staff in U.K. dermatology.

PMID- 16792783
TI  - Successful treatment of vulval melanoma in situ with topical 5% imiquimod cream.

PMID- 16792784
TI  - Prognostic factors for a subsequent basal cell carcinoma: implications for follow
      up.

PMID- 16792785
TI  - Epidermodysplasia verruciformis with severe hands and feet deformity successfully
      treated by surgical excision.

PMID- 16792786
TI  - Idiopathic polydactylous longitudinal erythronychia: a newly described entity.

PMID- 16792787
TI  - Wegener's granulomatosis presenting with granulomatous facial erythematous
      papules and plaques mimicking granulomatous rosacea.

PMID- 16792788
TI  - Cutaneous xanthomatosis: a novel presentation of hypercholesterolaemia in primary
      sclerosing cholangitis.

PMID- 16792789
TI  - Phacomatosis pigmentokeratotica associated with hypophosphataemic rickets,
      pheochromocytoma and multiple basal cell carcinomas.

PMID- 16792790
TI  - Vaginal bleeding after initiation of isotretinoin in a female-to-male transsexual
      on testosterone.

PMID- 16792791
TI  - Psoriasis management: considerations in women of childbearing age.

PMID- 16792792
TI  - Study protocol: home-based physical rehabilitation for survivors of a critical
      illness [ACTRN12605000166673].
AB  - INTRODUCTION: Numerous primary studies and several review papers have highlighted
      delayed physical and psychological recovery for survivors of critical illness,
      often beyond 6 months after discharge. This randomized controlled trial with
      blinded assessment aims to test the effects of an 8-week, home-based,
      individually tailored physical rehabilitation programme on physical and
      psychological recovery for survivors of a critical illness after discharge from
      hospital. METHOD: Participants are survivors of a critical illness discharged
      from nine intensive care units (ICUs) in Australia, who are aged 18 years or
      older, in an ICU longer than 48 hours, discharged home to self-care or carer (non
      institutional care), able to participate in physical rehabilitation, and within
      the hospitals' local geographical areas for home visits. The study is based in
      participants' home environments. Blinded assessments at weeks 1, 8 and 26 after
      hospital discharge examine physical functioning, exercise capacity, health
      related quality of life and psychological well being. The intervention is graded,
      individualized endurance and strength training prescribed by a pulmonary
      rehabilitation physiotherapist over an 8-week period, with three home visits,
      five follow-up phone calls, and a printed exercise manual supporting the
      training. Initial focus is on lower limb exercises and walking, with warm-up
      stretches, and progresses to the addition of core stabilization and upper limb
      exercises. RESULTS: The burden of a critical illness is well documented. This
      novel study will determine whether a home-based physical rehabilitation programme
      improves the recovery trajectory for survivors of critical illness. The projected
      sample size of 200 patients aims to detect a clinically important 10% improvement
      in physical functioning. The study will also examine whether other important
      physical and psychological measures are improved. CONCLUSION: This multicentre,
      randomized controlled trial will examine outcomes that are meaningful to
      patients, their family and society, namely functional ability and well being. The
      study will also target a health problem that is likely to increase as the
      population ages. If the programme is effective, it will provide a model that can
      be easily adapted and adopted by existing primary care or community services to
      improve the recovery of individuals following critical illness.

PMID- 16792793
TI  - Measurement of alveolar derecruitment in patients with acute lung injury:
      computerized tomography versus pressure-volume curve.
AB  - INTRODUCTION: Positive end-expiratory pressure (PEEP)-induced lung derecruitment
      can be assessed by a pressure-volume (P-V) curve method or by lung computed
      tomography (CT). However, only the first method can be used at the bedside. The
      aim of the study was to compare both methods for assessing alveolar derecruitment
      after the removal of PEEP in patients with acute lung injury or acute respiratory
      distress syndrome. METHODS: P-V curves (constant-flow method) and spiral CT scans
      of the whole lung were performed at PEEPs of 15 and 0 cmH2O in 19 patients with
      acute lung injury or acute respiratory distress syndrome. Alveolar derecruitment
      was defined as the difference in lung volume measured at an airway pressure of 15
      cmH2O on P-V curves performed at PEEPs of 15 and 0 cmH2O, and as the difference
      in the CT volume of gas present in poorly aerated and nonaerated lung regions at
      PEEPs of 15 and 0 cmH2O. RESULTS: Alveolar derecruitments measured by the CT and
      P-V curve methods were 373 +/- 250 and 345 +/- 208 ml (p = 0.14), respectively.
      Measurements by both methods were tightly correlated (R = 0.82, p < 0.0001). The
      derecruited volume measured by the P-V curve method had a bias of -14 ml and
      limits of agreement of between -158 and +130 ml in comparison with the average
      derecruited volume of the CT and P-V curve methods. CONCLUSION: Alveolar
      derecruitment measured by the CT and P-V curve methods are tightly correlated.
      However, the large limits of agreement indicate that the P-V curve and the CT
      method are not interchangeable.

PMID- 16792795
TI  - PHY.FI: fast and easy online creation and manipulation of phylogeny color
      figures.
AB  - BACKGROUND: The need to depict a phylogeny, or some other kind of abstract tree,
      is very frequently experienced by researchers from a broad range of biological
      and computational disciplines. Thousands of papers and talks include phylogeny
      figures, and often during everyday work, one would like to quickly get a
      graphical display of, e.g., the phylogenetic relationship between a set of
      sequences as calculated by an alignment program such as ClustalW or the
      phylogenetic package Phylip. A wealth of software tools capable of tree drawing
      exists; most are comprehensive packages that also perform various types of
      analysis, and hence they are available only for download and installing. Some
      online tools exist, too. RESULTS: This paper presents an online tool, PHY.FI,
      which encompasses all the qualities of existing online programs and adds
      functionality to hopefully eliminate the need for post-processing the phylogeny
      figure in some other general-purpose graphics program. PHY.FI is versatile, easy
      to-use and fast, and supports comprehensive graphical control, several download
      image formats, and the possibility of dynamically collapsing groups of nodes into
      named subtrees (e.g. "Primates"). The user can create a color figure from any
      phylogeny, or other kind of tree, represented in the widely used parenthesized
      Newick format. CONCLUSION: PHY.FI is fast and easy to use, yet still offers full
      color control, tree manipulation, and several image formats. It does not require
      any downloading and installing, and thus any internet user regardless of computer
      skills, and computer platform, can benefit from it. PHY.FI is free for all and is
      available from this web address: http://cgi-www.daimi.au.dk/cgi-chili/phyfi/go.

PMID- 16792794
TI  - Impact of funding on biomedical research: a retrospective cohort study.
AB  - BACKGROUND: Public funding is aimed at facilitating the initiation, completion
      and publication of research study protocols. However, no evaluation is made to
      investigate the impact of grant success on the conduct of biomedical research. It
      is therefore of great interest to compare the fate of funded protocols versus not
      funded: Are they initiated? Are they completed? Did the results confirm the
      hypothesis? Were they published? The objective was to investigate the fate of
      protocols submitted for funding, whether they were funded or not. METHODS:
      Retrospective cohort study of protocols submitted for funding to the Greater Lyon
      regional scientific committee in 1997. Initial characteristics of protocols
      (design, study size, investigator status) were abstracted from archives, and
      follow-up characteristics (initiation, completion and publication) from a mailed
      questionnaire to the principal investigators. RESULTS: Among the 142 submitted
      protocols, follow-up information was available for 114 (80%). As a whole, 38% of
      studies were funded by the Greater Lyon research committee. The rate of
      initiation varied from 62% for studies with no acknowledged funding to 100% for
      studies with both committee and other simultaneous funding. When initiated, the
      rate of completion was 62% for studies with at least one funding and 40% for
      studies without acknowledged funding. When completed, publication was reached for
      77% of studies with either committee or external funding, for 58% of studies
      without acknowledged funding and for 37% of studies with both committee and
      external funding. CONCLUSION: Some protocols submitted for funding were initiated
      and completed without any funding declared. To our understanding this mean that
      not all protocols submitted really needed funding and also that health care
      facilities are unaware that they implicitly financially support and pay for
      biomedical research.

PMID- 16792796
TI  - Histological response of peritoneal carcinomatosis after hyperthermic
      intraperitoneal chemoperfusion (HIPEC) in experimental investigations.
AB  - BACKGROUND: In selected patients with peritoneal carcinomatosis from colorectal
      cancer prognosis can be improved by hyperthermic intraperitoneal chemotherapy
      (HIPEC) after cytoreductive surgery. The aim of this study was to evaluate the
      tumor response of peritoneal carcinomatosis in tumor-bearing rats treated with
      HIPEC. METHODS: CC531 colon carcinoma (2,5 x 106 cells), implanted
      intraperitoneally in Wag/Rija rats, was treated by hyperthermic intraperitoneal
      chemotherapy. After 10 days of tumor growth the animals were randomized into five
      groups of six animals each: group I: control (n = 6), group II: sham operated
      animals (n = 6), group III: hyperthermic intraperitoneal perfusion (HIP) without
      cytostatic drugs, group IV: HIPEC with mitomycin C in a concentration of 15 mg/m2
      (n = 6), group V: mitomycin C i.p. alone in a concentration of 10 mg/m2 (n = 6).
      After 10 days the extent of tumor spread and histological outcome were analysed
      by autopsy. RESULTS: All control animals developed extensive intraperitoneal
      tumor growth. Histological tumor load was significantly reduced in group III and
      group V and was lowest in group IV. In group II tumor load was significantly
      higher than in group I. Implanted metastases were significantly decreased in
      group IV compared with group I and group II. CONCLUSION: These findings indicate
      that HIPEC is an effective treatment for peritoneal carcinomatosis in this animal
      model. HIPEC reduced macroscopic and microscopic intraperitoneal tumor spread.

PMID- 16792798
TI  - How much does pre-trial testing influence complex intervention trials and would
      more testing make any difference? An email survey.
AB  - BACKGROUND: The UK Medical Research Council has proposed that complex
      interventions should be tested in exploratory trials prior to a full-scale trial
      so as to better define the intervention and test the feasibility of components
      such as recruitment. It is not clear to what extent this is being done. This
      study aimed to determine to what extent complex interventions are tested prior to
      a full-scale trial and whether more or different testing would have led to a
      different intervention being used in the trial. METHODS: Email survey of the
      authors of complex intervention trials published in seven major journals in 2004.
      RESULTS: 72% (50/69) of eligible authors replied. Eight authors did not consider
      their interventions to be complex. The majority of respondents' complex
      interventions were tested (34/42): some extensively. Conversely, only 17 of the
      34 published reports describing these trials mention testing. Two-thirds (22/34)
      of those testing their interventions did not believe that more or different
      testing would have produced a more effective intervention. 31% (13/42) of all
      authors did believe further testing would have led to improvements. Five
      respondents mentioned a lack of funding as a reason for not doing more testing.
      CONCLUSION: Complex interventions are generally tested prior to their evaluation
      in a full-scale trial, although the amount of testing varies. Testing is often
      not described in trial reports, which makes it hard to judge whether a trial
      result could be improved with a better intervention, or whether further work with
      a different intervention is required.

PMID- 16792797
TI  - Clinical management and microscopic characterisation of fatigue-induced failure
      of a dental implant. Case report.
AB  - BACKGROUND: Osseointegrated endosseous implants are widely used for the
      rehabilitation of completely and partially edentulous patients, being the final
      prosthodontic treatment more predictable and the failures extremely infrequent. A
      case of fracture of an endosseous dental implant, replacing the maxillary first
      molar, occurring in a middle-age woman, 5 years after placement is reported.
      MATERIALS AND METHODS: The difficult management of this rare complication of
      implant dentistry together with the following rehabilitation is described.
      Additionally, the authors performed an accurate analysis of the removed fractured
      implant both by the stereomicroscope and by the confocal laser scanning
      microscope. RESULTS AND DISCUSSION: The fractured implant showed the typical
      signs of a fatigue-induced fracture in the coronal portion of the implant
      together with numerous micro-fractures in the apical one. Three dimensional
      imaging performed by confocal laser scanning microscope led easily to a diagnosis
      of "fatigue fracture" of the implant. The biomechanical mechanism of implant
      fractures when overstress of the implant components due to bending overload is
      discussed. CONCLUSION: When a fatigue-induced fracture of an dental implant
      occurs in presence of bending overload, the whole implant suffers a deformation
      that is confirmed by the alterations (micro-fractures) of the implant observable
      also in the osseointegrated portion that is easily appraisable by the use of
      stereomicroscope and confocal laser scanning microscope without preparation of
      the sample.

PMID- 16792799
TI  - Gastrointestinal failure in intensive care: a retrospective clinical study in
      three different intensive care units in Germany and Estonia.
AB  - BACKGROUND: While gastrointestinal problems are common in ICU patients with
      multiple organ failure, gastrointestinal failure has not been given the
      consideration other organ systems receive. The aim of this study was to evaluate
      the incidence of gastrointestinal failure (GIF), to identify its risk factors,
      and to determine its association with ICU mortality. METHODS: A retrospective
      analysis of adult patients (n = 2588) admitted to three different ICUs (two ICUs
      at the university hospital Charite-Universitatsmedizin Berlin, Germany and one at
      Tartu University Clinics, Estonia) during the year 2002 was performed. Data
      recorded in a computerized database were used in Berlin. In Tartu, the data
      documented in the patients' charts was retrospectively transferred into a similar
      database. GIF was defined as documented gastrointestinal problems (food
      intolerance, gastrointestinal haemorrhage, and/or ileus) in the patient data at
      any period of their ICU stay. ICU mortality, length of stay, and duration of
      mechanical ventilation were assessed as outcome parameters. RESULTS: GIF was
      identified in 252 patients (9.7% of all patients). Only 20% of GIF patients were
      identifiable at admission. GIF was related to significantly higher mortality
      (43.7% vs. 5.3% in patients without GIF), as well as prolonged length of ICU stay
      (10 vs. 2 days) and mechanical ventilation (8 vs. 1 day), p < 0.001,
      respectively. Patients' profile (emergency surgical or medical), APACHE II and
      SOFA scores and the use of catecholamines at admission were identified as
      independent risk factors for the development of GIF. Development of GIF during
      ICU stay was an independent predictor for death. CONCLUSION: Gastrointestinal
      failure represents a relevant clinical problem accompanied by an increased
      mortality, longer ICU stay and mechanical ventilation.

PMID- 16792800
TI  - The prevalence of pseudoexfoliation syndrome in Pakistan. Hospital based study.
AB  - BACKGROUND: Pseudoexfoliation syndrome (PXS) is the most common identifiable
      cause of secondary glaucoma, the prevalence of which varies considerably among
      different ethnicities. The aim of this study was to assess the prevalence of
      pseudoexfoliation syndrome in Pakistan. METHODS: A prospective study conducted in
      the period from January 2003 to June 2004 in a teaching hospital serving a
      population of about 7.6 million. 1860 patients aged 45 or above attending the
      general ophthalmic clinics were recruited for this study. A detailed evaluation
      including ophthalmic and general history, slit lamp biomicroscopy, intraocular
      pressure measurement, gonioscopy and dilated eye examination was performed on all
      patients. RESULTS: 120(6.45%) subjects were found to have PXS with a male to
      female ratio of 1.5:1. All 120 (100%) cases were bilateral and 48(40%) patients
      had high intraocular pressure. CONCLUSION: To the best of our knowledge, this is
      the first study conducted in a Pakistani population to determine the prevalence
      of PXS. The prevalence rate of 6.45% is similar to other studies conducted in
      south Asia, however all cases were bilateral and quite a high percentage of
      patients had high intra-ocular pressure.

PMID- 16792802
TI  - PHOG-BLAST--a new generation tool for fast similarity search of protein families.
AB  - BACKGROUND: The need to compare protein profiles frequently arises in various
      protein research areas: comparison of protein families, domain searches,
      resolution of orthology and paralogy. The existing fast algorithms can only
      compare a protein sequence with a protein sequence and a profile with a sequence.
      Algorithms to compare profiles use dynamic programming and complex scoring
      functions. RESULTS: We developed a new algorithm called PHOG-BLAST for fast
      similarity search of profiles. This algorithm uses profile discretization to
      convert a profile to a finite alphabet and utilizes hashing for fast search. To
      determine the optimal alphabet, we analyzed columns in reliable multiple
      alignments and obtained column clusters in the 20-dimensional profile space by
      applying a special clustering procedure. We show that the clustering procedure
      works best if its parameters are chosen so that 20 profile clusters are obtained
      which can be interpreted as ancestral amino acid residues. With these clusters,
      only less than 2% of columns in multiple alignments are out of clusters. We
      tested the performance of PHOG-BLAST vs. PSI-BLAST on three well-known databases
      of multiple alignments: COG, PFAM and BALIBASE. On the COG database both
      algorithms showed the same performance, on PFAM and BALIBASE PHOG-BLAST was much
      superior to PSI-BLAST. PHOG-BLAST required 10-20 times less computer memory and
      computation time than PSI-BLAST. CONCLUSION: Since PHOG-BLAST can compare
      multiple alignments of protein families, it can be used in different areas of
      comparative proteomics and protein evolution. For example, PHOG-BLAST helped to
      build the PHOG database of phylogenetic orthologous groups. An essential step in
      building this database was comparing protein complements of different species and
      orthologous groups of different taxons on a personal computer in reasonable time.
      When it is applied to detect weak similarity between protein families, PHOG-BLAST
      is less precise than rigorous profile-profile comparison method, though it runs
      much faster and can be used as a hit pre-selecting tool.

PMID- 16792801
TI  - Differentiated evolutionary rates in alternative exons and the implications for
      splicing regulation.
AB  - BACKGROUND: Alternatively spliced exons play an important role in the
      diversification of gene function in most metazoans and are highly regulated by
      conserved motifs in exons and introns. Two contradicting properties have been
      associated to evolutionary conserved alternative exons: higher sequence
      conservation and higher rate of non-synonymous substitutions, relative to
      constitutive exons. In order to clarify this issue, we have performed an analysis
      of the evolution of alternative and constitutive exons, using a large set of
      protein coding exons conserved between human and mouse and taking into account
      the conservation of the transcript exonic structure. Further, we have also
      defined a measure of the variation of the arrangement of exonic splicing
      enhancers (ESE-conservation score) to study the evolution of splicing regulatory
      sequences. We have used this measure to correlate the changes in the arrangement
      of ESEs with the divergence of exon and intron sequences. RESULTS: We find
      evidence for a relation between the lack of conservation of the exonic structure
      and the weakening of the sequence evolutionary constraints in alternative and
      constitutive exons. Exons in transcripts with non-conserved exonic structures
      have higher synonymous (dS) and non-synonymous (dN) substitution rates than exons
      in conserved structures. Moreover, alternative exons in transcripts with non
      conserved exonic structure are the least constrained in sequence evolution, and
      at high EST-inclusion levels they are found to be very similar to constitutive
      exons, whereas alternative exons in transcripts with conserved exonic structure
      have a dS significantly lower than average at all EST-inclusion levels. We also
      find higher conservation in the arrangement of ESEs in constitutive exons
      compared to alternative ones. Additionally, the sequence conservation at flanking
      introns remains constant for constitutive exons at all ESE-conservation values,
      but increases for alternative exons at high ESE-conservation values. CONCLUSION:
      We conclude that most of the differences in dN observed between alternative and
      constitutive exons can be explained by the conservation of the transcript exonic
      structure. Low dS values are more characteristic of alternative exons with
      conserved exonic structure, but not of those with non-conserved exonic structure.
      Additionally, constitutive exons are characterized by a higher conservation in
      the arrangement of ESEs, and alternative exons with an ESE-conservation similar
      to that of constitutive exons are characterized by a conservation of the flanking
      intron sequences higher than average, indicating the presence of more intronic
      regulatory signals.

PMID- 16792803
TI  - PHOG: a database of supergenomes built from proteome complements.
AB  - BACKGROUND: Orthologs and paralogs are widely used terms in modern comparative
      genomics. Existing procedures for resolving orthologous/paralogous relationships
      are often based on manual revision of clusters of orthologous groups and/or lack
      any rigorous evolutionary base. DESCRIPTION: We developed a completely automated
      procedure that creates clusters of orthologous groups at each node of the
      taxonomy tree (PHOGs--Phylogenetic Orthologous Groups). As a result of this
      procedure, a tree of orthologous groups was obtained. Each cluster is a
      "supergene" and it is represented by an "ancestral" sequence obtained from the
      multiple alignment of orthologous and paralogous genes. The procedure has been
      applied to the taxonomy tree of organisms from all three domains of life. Protein
      complements from 50 bacterial, archaeal and eukaryotic species were used to
      create PHOGs at all tree nodes. 51367 PHOGs were obtained at the root node.
      CONCLUSION: The PHOG database demonstrates that it is possible to automatically
      process any number of sequenced genomes and to reconstruct orthologous and
      paralogous relationships between genomes using a rigorous evolutionary approach.
      This database can become a very useful tool in various areas of comparative
      genomics.

PMID- 16792804
TI  - Disjunction of conjoined twins: Cdk1, Cdh1 and separation of centrosomes.
AB  - Accurate transmission of chromosomes from parent to progeny cell requires
      assembly of a bipolar spindle. Centrosomes (spindle pole body in yeast) are
      critical for the biogenesis of this complex mitotic apparatus since they confer
      bipolarity on the spindle and serve as the site of microtubule polymerization. In
      each division cycle, the centrosome is duplicated and the sister-centrosomes move
      away from each other, forming the two poles of the spindle. While the structure
      and the duplication of centrosomes have been investigated extensively, the
      understanding of the control of their segregation remains scant. Recent findings
      are beginning to yield insights into the regulation of centrosome segregation in
      yeast and its link to the mitotic kinase.

PMID- 16792805
TI  - Reduced CD4 T cell activation and in vitro susceptibility to HIV-1 infection in
      exposed uninfected Central Africans.
AB  - BACKGROUND: Environmentally driven immune activation was suggested to contribute
      to high rates of HIV-1 infection in Africa. We report here a study of immune
      activation markers and susceptibility to HIV-1 infection in vitro of forty-five
      highly exposed uninfected partners (EUs) of HIV-1 infected individuals in Central
      African Republic, in comparison with forty-four low-risk blood donors (UCs).
      RESULTS: Analysis of T lymphocyte subsets and activation markers in whole blood
      showed that the absolute values and the percentage of HLA-DR+CD4 T cells and of
      CCR5+CD4 T cells were lower in the EUs than in the UCs (p = 0.0001). Mutations in
      the CCR5 coding region were not found in either group. Susceptibility to in vitro
      infection of unstimulated peripheral blood mononuclear cells, prior of PHA
      activation, was decreased in EUs compared to UCs, either using a CXCR4-tropic or
      a CCR5-tropic HIV-1 strain (p = 0.02 and p = 0.05, respectively). Levels of MIP
      1beta, but not of MIP-1alpha or RANTES, in the supernatants of PHA-activated
      PBMC, were higher in the EUs than in the UCs (p = 0.007). CONCLUSION: We found
      low levels of CD4 T cell activation and reduced PBMC susceptibility to HIV-1
      infection in Central African EUs, indicating that both may contribute to the
      resistance to HIV-1 infection.

PMID- 16792807
TI  - Effects of tegaserod on bile composition and hepatic secretion in Richardson
      ground squirrels on an enriched cholesterol diet.
AB  - BACKGROUND: Tegaserod is effective in treating IBS patients with constipation,
      and does not alter gallbladder motility in healthy individuals or in patients
      with IBS. However, it is not known if tegaserod affects the biliary tract in
      gallstone disease, so to this end the effects of tegaserod on bile composition
      and hepatic secretion of Richardson ground squirrels maintained on an enriched
      cholesterol diet were examined. RESULTS: Animals were fed either a control
      (0.03%) or enriched (1%) cholesterol diet for 28 days, and treated s.c. with
      tegaserod (0.1 mg/kg BID) or vehicle. Bile flow, bile acid, phospholipids and
      cholesterol secretion were measured with standard methods. Tegaserod treatment or
      enriched cholesterol diet, alone or combination, did not alter body or liver
      weights. The enriched cholesterol diet increased cholesterol saturation index
      (CSI), cholesterol concentrations in gallbladder and hepatic duct bile by
      approximately 50% and decreased bile acids in gallbladder bile by 17%. Tegaserod
      treatment reversed these cholesterol-induced changes. None of the treatments,
      drug or diet, altered fasting gallbladder volume, bile flow and bile salts or
      phospholipid secretion in normal diet and cholesterol-fed animals. However,
      tegaserod treatment prevented the decreases in bile acid pool size and cycling
      frequency caused by the enriched cholesterol diet, consequent to re-establishing
      normal bile acid to concentrations in the gall bladder. Tegaserod had no effect
      on these parameters with normal diet animals. CONCLUSION: Tegaserod treatment
      results in increased enterohepatic cycling and lowers cholesterol saturation in
      the bile of cholesterol-fed animals. These effects would decrease conditions
      favorable to cholesterol gallstone formation.

PMID- 16792806
TI  - Insulin-like growth factor-1 (IGF-1) induces the activation/phosphorylation of
      Akt kinase and cAMP response element-binding protein (CREB) by activating
      different signaling pathways in PC12 cells.
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-1) is a polypeptide growth factor
      with a variety of functions in both neuronal and non-neuronal cells. IGF-1 plays
      anti-apoptotic and other functions by activating multiple signaling pathways
      including Akt kinase, a serine/threonine kinase essential for cell survival. The
      nuclear transcription factor cAMP response element-binding protein (CREB) may
      also be involved although relationships between these two proteins in IGF-1
      receptor signaling and protection is not clear, especially in neuronal cells.
      RESULTS: IGF-1, in a concentration- and time-dependent manner, induces the
      activation/phosphorylation of Akt and CREB in PC12 cells by activating different
      signaling pathways. IGF-1 induced a sustained phosphorylation of Akt while only a
      transient one was seen for CREB. The phosphorylation of Akt is mediated by the
      PI3 kinase pathway while that of CREB is dependent on the activation of both MAPK
      kinase and p38 MAPK. Moreover, the stimulation of PKC attenuated the
      phosphorylation of Akt induced by IGF-1 while enhancing that of CREB. Survival
      assays with various kinase inhibitors suggested that the
      activation/phosphorylation of both Akt and CREB contributes to IGF-1 mediated
      cell survival in PC12 cells. CONCLUSION: These data suggest that IGF-1 induced
      the activation of Akt and CREB using distinct pathways in PC12 cells.

PMID- 16792809
TI  - Primary intra-abdominal malignant fibrous histiocytoma presenting as pyrexia of
      unknown origin--report of a case with review of literature.
AB  - Primary intra-abdominal malignant mesenchymal tumours are very rare and there are
      not many cases of visceral malignant fibrous histiocytoma in the English
      literature. We report a new case of abdominal malignant fibrous histiocytoma
      presenting as abdominal pain and pyrexia of unknown origin in a 54 year old
      female followed by a brief review of literature. Presentation with pyrexia of
      unknown origin is extremely rare in this condition.

PMID- 16792808
TI  - Sustained inflation and incremental mean airway pressure trial during
      conventional and high-frequency oscillatory ventilation in a large porcine model
      of acute respiratory distress syndrome.
AB  - BACKGROUND: To compare the effect of a sustained inflation followed by an
      incremental mean airway pressure trial during conventional and high-frequency
      oscillatory ventilation on oxygenation and hemodynamics in a large porcine model
      of early acute respiratory distress syndrome. METHODS: Severe lung injury (Ali)
      was induced in 18 healthy pigs (55.3 +/- 3.9 kg, mean +/- SD) by repeated saline
      lung lavage until PaO2 decreased to less than 60 mmHg. After a stabilisation
      period of 60 minutes, the animals were randomly assigned to two groups: Group 1
      (Pressure controlled ventilation; PCV): FIO2 = 1.0, PEEP = 5 cmH2O, V(T) = 6
      ml/kg, respiratory rate = 30/min, I:E = 1:1; group 2 (High-frequency oscillatory
      ventilation; HFOV): FIO2 = 1.0, Bias flow = 30 l/min, Amplitude = 60 cmH2O,
      Frequency = 6 Hz, I:E = 1:1. A sustained inflation (SI; 50 cmH2O for 60s)
      followed by an incremental mean airway pressure (mPaw) trial (steps of 3 cmH2O
      every 15 minutes) were performed in both groups until PaO2 no longer increased.
      This was regarded as full lung inflation. The mPaw was decreased by 3 cmH2O and
      the animals reached the end of the study protocol. Gas exchange and hemodynamic
      data were collected at each step. RESULTS: The SI led to a significant
      improvement of the PaO2/FiO2-Index (HFOV: 200 +/- 100 vs. PCV: 58 +/- 15 and
      T(Ali): 57 +/- 12; p < 0.001) and PaCO2-reduction (HFOV: 42 +/- 5 vs. PCV: 62 +/-
      13 and T(Ali): 55 +/- 9; p < 0.001) during HFOV compared to lung injury and PCV.
      Augmentation of mPaw improved gas exchange and pulmonary shunt fraction in both
      groups, but at a significant lower mPaw in the HFOV treated animals. Cardiac
      output was continuously deteriorating during the recruitment manoeuvre in both
      study groups (HFOV: T(Ali): 6.1 +/- 1 vs. T(75): 3.4 +/- 0.4; PCV: T(Ali): 6.7 +/
      2.4 vs. T(75): 4 +/- 0.5; p < 0.001). CONCLUSION: A sustained inflation followed
      by an incremental mean airway pressure trial in HFOV improved oxygenation at a
      lower mPaw than during conventional lung protective ventilation. HFOV but not PCV
      resulted in normocapnia, suggesting that during HFOV there are alternatives to
      tidal ventilation to achieve CO2-elimination in an "open lung" approach.

PMID- 16792810
TI  - Family planning services quality as a determinant of use of IUD in Egypt.
AB  - BACKGROUND: Both availability and quality of family planning services are
      believed to have contributed to increasing contraceptive use and declining
      fertility rates in developing countries. Yet, there is limited empirical evidence
      to show the relationship between the quality of family planning services and the
      population based prevalence of contraceptive methods. This study examined the
      relationship between quality of family planning services and use of intrauterine
      devices (IUD) in Egypt. METHODS: The analysis used data from the 2003 Egypt
      Interim Demographic and Health Survey (EIDHS) that included 8,445 married women
      aged 15-49, and the 2002 Egypt Service Provision Assessment (ESPA) survey that
      included 602 facilities offering family planning services. The EIDHS collected
      latitude and longitude coordinates of all sampled clusters, and the ESPA
      collected these coordinates for all sampled facilities. Using Geographic
      Information System (GIS) methods, individual women were linked to a facility
      located within 10 km of their community. A facility-level index was constructed
      to reflect the quality of family planning services. Four dimensions of quality of
      care were examined: counseling, examination room, supply of contraceptive
      methods, and management. Effects of quality of family planning services on the
      use of IUD and other contraceptive methods were estimated using multinomial
      logistic regression. Results are presented as relative risk ratios (RRR) with
      significance levels (p-values). RESULTS: IUD use among women who obtained their
      method from public sources was significantly positively associated with quality
      of family planning services (RRR = 1.36, p < 0.01), independent of distance to
      the facility, facility type, age, number of living children, education level,
      household wealth status, and residence. Quality of services related to counseling
      and examination room had strong positive effects on use of IUD (RRR = 1.61 for
      counseling and RRR = 1.46 for examination room). Obtaining IUD from a private
      source or using other contraceptive methods was not associated with quality of
      services. CONCLUSION: This study is one among the few that used geographic
      information to link data from a population-based survey with an independently
      sampled health facility survey. The findings demonstrate that service quality is
      an important determinant of use of clinical contraceptive methods in Egypt.
      Improving quality of family planning services may help further increase use of
      clinical contraceptive methods and reduce fertility.

PMID- 16792811
TI  - CAVER: a new tool to explore routes from protein clefts, pockets and cavities.
AB  - BACKGROUND: The main aim of this study was to develop and implement an algorithm
      for the rapid, accurate and automated identification of paths leading from buried
      protein clefts, pockets and cavities in dynamic and static protein structures to
      the outside solvent. RESULTS: The algorithm to perform a skeleton search was
      based on a reciprocal distance function grid that was developed and implemented
      for the CAVER program. The program identifies and visualizes routes from the
      interior of the protein to the bulk solvent. CAVER was primarily developed for
      proteins, but the algorithm is sufficiently robust to allow the analysis of any
      molecular system, including nucleic acids or inorganic material. Calculations can
      be performed using discrete structures from crystallographic analysis and NMR
      experiments as well as with trajectories from molecular dynamics simulations. The
      fully functional program is available as a stand-alone version and as plug-in for
      the molecular modeling program PyMol. Additionally, selected functions are
      accessible in an online version. CONCLUSION: The algorithm developed
      automatically finds the path from a starting point located within the interior of
      a protein. The algorithm is sufficiently rapid and robust to enable routine
      analysis of molecular dynamics trajectories containing thousands of snapshots.
      The algorithm is based on reciprocal metrics and provides an easy method to find
      a centerline, i.e. the spine, of complicated objects such as a protein tunnel. It
      can also be applied to many other molecules. CAVER is freely available from the
      web site http://loschmidt.chemi.muni.cz/caver/.

PMID- 16792812
TI  - Physician-assisted suicide: a review of the literature concerning practical and
      clinical implications for UK doctors.
AB  - BACKGROUND: A bill to legalize physician-assisted suicide in the UK recently made
      significant progress in the British House of Lords and will be reintroduced in
      the future. Until now there has been little discussion of the clinical
      implications of physician-assisted suicide for the UK. This paper describes
      problematical issues that became apparent from a review of the medical and
      psychiatric literature as to the potential effects of legalized physician
      assisted suicide. DISCUSSION: Most deaths by physician-assisted suicide are
      likely to occur for the illness of cancer and in the elderly. GPs will deal with
      most requests for assisted suicide. The UK is likely to have proportionately more
      PAS deaths than Oregon due to the bill's wider application to individuals with
      more severe physical disabilities. Evidence from other countries has shown that
      coercion and unconscious motivations on the part of patients and doctors in the
      form of transference and countertransference contribute to the misapplication of
      physician-assisted suicide. Depression influences requests for hastened death in
      terminally ill patients, but is often under-recognized or dismissed by doctors,
      some of whom proceed with assisted death anyway. Psychiatric evaluations, though
      helpful, do not solve these problems. Safeguards that are incorporated into
      physician-assisted suicide criteria probably decrease but do not prevent its
      misapplication. SUMMARY: The UK is likely to face significant clinical problems
      arising from physician-assisted suicide if it is legalized. Terminally ill
      patients with mental illness, especially depression, are particularly vulnerable
      to the misapplication of physician-assisted suicide despite guidelines and
      safeguards.

PMID- 16792814
TI  - Blood donors' motivation and attitude to non-remunerated blood donation in
      Lithuania.
AB  - BACKGROUND: In the Soviet period, the blood donation system operated in Lithuania
      exclusively on a remunerative basis. After joining the EU, Lithuania committed
      itself to meeting the EU requirements to provide all consumers within its
      boundaries with safe blood products made from voluntary unpaid blood donations.
      However, the introduction of a non-remunerated donation system may considerably
      affect donors' motivation and retention. Thus the aim of the current research was
      to determine blood donation motives among the present donors and investigate
      their attitude towards non-remunerated donation. METHODS: A questionnaire survey
      of 400 blood donors. Survey data processed using SPSS statistical analysis
      package. Statistical data reliability checked using Fisher's exact test (p <
      0.05). RESULTS: Paid donors comprised 89.9%, while non-paid ones made 10.1% of
      the respondents. Research findings show that 93 per cent of the paid donors give
      blood on a regular basis; while among the non-remunerated donors the same figure
      amounted merely to 20.6 per cent. The idea of the remuneration necessity is
      supported by 78.3 per cent of the paid donors, while 64.7 per cent of the non
      remunerated respondents believe that remuneration is not necessary. The absolute
      majority of the paid donors (92%) think they should be offered a monetary
      compensation for blood donation, while more than half of the non-remunerated
      donors (55.9) claim they would be content with a mere appreciation of the act.
      Provided no remuneration were offered, 28.44 per cent of the respondents would
      carry on doing it, 29.6 per cent would do it only in emergency, 29.6 per cent
      would donate blood merely for their family or friends, and 12.3 per cent would
      quit it completely. CONCLUSION: Most respondents admitted having donated blood
      for the following reasons: willingness to help the ill or monetary compensation.
      Majority would consent to free blood donation only in case of emergency or as a
      family replacement, which leads to a conclusion that provided monetary
      remuneration is completely terminated part of the currently active paid donors
      would withdraw from this activity, which might seriously affect the national
      supply of blood and its products.

PMID- 16792813
TI  - PSMIX: an R package for population structure inference via maximum likelihood
      method.
AB  - BACKGROUND: Inference of population stratification and individual admixture from
      genetic markers is an integrative part of a study in diverse situations, such as
      association mapping and evolutionary studies. Bayesian methods have been proposed
      for population stratification and admixture inference using multilocus genotypes
      and widely used in practice. However, these Bayesian methods demand intensive
      computation resources and may run into convergence problem in Markov Chain Monte
      Carlo based posterior samplings. RESULTS: We have developed PSMIX, an R package
      based on maximum likelihood method using expectation-maximization algorithm, for
      inference of population stratification and individual admixture. CONCLUSION:
      Compared with software based on Bayesian methods (e.g., STRUCTURE), PSMIX has
      similar accuracy, but more efficient computations.PSMIX and its supplemental
      documents are freely available at http://bioinformatics.med.yale.edu/PSMIX.

PMID- 16792815
TI  - In planta production of two peptides of the Classical Swine Fever Virus (CSFV) E2
      glycoprotein fused to the coat protein of potato virus X.
AB  - BACKGROUND: Classical Swine Fever (CSFV) is one of the most important viral
      infectious diseases affecting wild boars and domestic pigs. The etiological agent
      of the disease is the CSF virus, a single stranded RNA virus belonging to the
      family Flaviviridae. All preventive measures in domestic pigs have been focused
      in interrupting the chain of infection and in avoiding the spread of CSFV within
      wild boars as well as interrupting transmission from wild boars to domestic pigs.
      The use of plant based vaccine against CSFV would be advantageous as plant organs
      can be distributed without the need of particular treatments such as
      refrigeration and therefore large areas, populated by wild animals, could be
      easily covered. RESULTS: We report the in planta production of peptides of the
      classical swine fever (CSF) E2 glycoprotein fused to the coat protein of potato
      virus X. RT-PCR studies demonstrated that the peptide encoding sequences are
      correctly retained in the PVX construct after three sequential passage in
      Nicotiana benthamiana plants. Sequence analysis of RT-PCR products confirmed that
      the epitope coding sequences are replicated with high fidelity during PVX
      infection. Partially purified virions were able to induce an immune response in
      rabbits. CONCLUSION: Previous reports have demonstrated that E2 synthetic
      peptides can efficiently induce an immunoprotective response in immunogenized
      animals. In this work we have showed that E2 peptides can be expressed in planta
      by using a modified PVX vector. These results are particularly promising for
      designing strategies for disease containment in areas inhabited by wild boars.

PMID- 16792816
TI  - Prediction of transmembrane helix orientation in polytopic membrane proteins.
AB  - BACKGROUND: Membrane proteins compose up to 30% of coding sequences within
      genomes. However, their structure determination is lagging behind compared with
      soluble proteins due to the experimental difficulties. Therefore, it is important
      to develop reliable computational methods to predict structures of membrane
      proteins. RESULTS: We present a method for prediction of the TM helix
      orientation, which is an essential step in ab initio modeling of membrane
      proteins. Our method is based on a canonical model of the heptad repeat
      originally developed for coiled coils. We identify the helical surface patches
      that interface with lipid molecules at an accuracy of about 88% from the sequence
      information alone, using an empirical scoring function LIPS (LIPid-facing
      Surface), which combines lipophilicity and conservation of residues in the helix.
      We test and discuss results of prediction of helix-lipid interfaces on 162
      transmembrane helices from 18 polytopic membrane proteins and present predicted
      orientations of TM helices in TRPV1 channel. We also apply our method to two
      structures of homologous cytochrome b6f complexes and find discrepancy in the
      assignment of TM helices from subunits PetG, PetN and PetL. The results of LIPS
      calculations and analysis of packing and H-bonding interactions support the helix
      assignment found in the cytochrome b6f structure from green alga but not the
      assignment of TM helices in the cyanobacterium b6f structure. CONCLUSION: LIPS
      calculations can be used for the prediction of helix orientation in ab initio
      modeling of polytopic membrane proteins. We also show with the example of two
      cytochrome b6f structures that our method can identify questionable helix
      assignments in membrane proteins. The LIPS server is available online at
      http://gila.bioengr.uic.edu/lab/larisa/lips.html.

PMID- 16792817
TI  - Targeting of small molecule anticancer drugs to the tumour and its vasculature
      using cationic liposomes: lessons from gene therapy.
AB  - Cationic (positively charged) liposomes have been tested in various gene therapy
      clinical trials for neoplastic and other diseases. They have demonstrated
      selectivity for tumour vascular endothelial cells raising hopes for both
      antiangiogenic and antivascular therapies. They are also capable of being
      selectively delivered to the lungs and liver when administered intravenously.
      These vesicles are being targeted to the tumour in various parts of the body by
      using advanced liposomal systems such as ligand-receptor and antibody-antigen
      combinations. At present, the transferrin receptor is commonly used for cancer
      targeted drug delivery systems including cationic liposomes. This review looks at
      the growing utility of these vesicles for delivery of small molecule anticancer
      drugs.

PMID- 16792818
TI  - Histopathological evaluation of ocular microsporidiosis by different stains.
AB  - BACKGROUND: There is limited data on comparing stains in the detection of
      microsporidia in corneal biopsies. Hence we wanted to evaluate various stains for
      their ability to detect microsporidia in corneal tissue sections. METHODS: Four
      cases diagnosed with microsporidiosis on Hematoxylin and Eosin and Periodic Acid
      Schiff's stained sections of the corneal button between January 2002 and December
      2004, were included. Further sections were prospectively stained with calcofluor
      white, Gram, Giemsa, Masson's trichrome, acridine orange, Gomori's methenamine
      silver, Gram's chromotrope and modified acid fast stain. The stained sections
      were analyzed for the spore characteristics in terms of size, shape, color
      contrast, cell wall morphology, waist band in cytoplasm and ease of detection.
      RESULTS: All sections showed microsporidial spores as 3-5 microm, oval bodies. 1%
      acid fast, Gram's chromotrope and GMS stains provided a reliable diagnosis of
      microsporidia as diagnostic waist band could be identified and good contrast
      helped distinguish the spores from inflammatory debris. CONCLUSION: Considering
      the ease of performance, cost effectiveness and rapidity of the technique, 1%
      acid fast stain and Gram's chromotrope stain are ideal for the detection of
      microsporidia.

PMID- 16792819
TI  - Hepatitis B and C: prevalence and risk factors associated with seropositivity
      among children in Karachi, Pakistan.
AB  - BACKGROUND: Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV)
      can lead to chronic liver disease and hepato-cellular carcinoma (HCC). This cross
      sectional study estimated the prevalence and identified risk factors associated
      with Hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV) sero
      positivity among children 1 to 15 years of age. METHODS: The study targeted the
      low to middle socioeconomic population that comprises 80% to 85% of the
      population. Consent was obtained from parents of the eligible children before
      administering questionnaire and collected a blood sample for anti-HCV and HBsAg
      serology. RESULTS: 3533 children were screened for HBsAg and anti-HCV. 1826 (52
      %) were males. 65 (1.8 %) were positive for HBsAg, male to female ratio 38:27;
      mean age 10 +/- 4 years. 55 (1.6 %) were positive for anti-HCV with a mean age 9
      +/- 4 years. 3 (0.11%) boys were positive for both HBsAg and anti-HCV. The
      overall infection rate was 3.3 % in the studied population. Hepatitis BsAg was
      more prevalent in subjects who received therapeutic injections 45 (69.2%)
      positive [Odd Ratio OR = 2.2; 95% Confidence interval CI: 1.3-3.6] inspite of
      using new needle and syringe 44 (67.7%) positive [OR = 2.2; 95% CI: 1.3-3.7] and
      vaccination in the government healthcare facilities 46 (70.7 %) positive with [OR
      = 3.0; 95% CI: 1.4-6.4]. These factors were not significant in anti-HCV positive
      cases. CONCLUSION: There is a need to educate general population regarding HBV
      and HCV infection and risks associated with inappropriate therapeutic injections.
      Hepatitis B vaccine should be administered to all newborns regardless of maternal
      HBsAg status.

PMID- 16792820
TI  - MACSIMS: multiple alignment of complete sequences information management system.
AB  - BACKGROUND: In the post-genomic era, systems-level studies are being performed
      that seek to explain complex biological systems by integrating diverse resources
      from fields such as genomics, proteomics or transcriptomics. New information
      management systems are now needed for the collection, validation and analysis of
      the vast amount of heterogeneous data available. Multiple alignments of complete
      sequences provide an ideal environment for the integration of this information in
      the context of the protein family. RESULTS: MACSIMS is a multiple alignment-based
      information management program that combines the advantages of both knowledge
      based and ab initio sequence analysis methods. Structural and functional
      information is retrieved automatically from the public databases. In the multiple
      alignment, homologous regions are identified and the retrieved data is evaluated
      and propagated from known to unknown sequences with these reliable regions. In a
      large-scale evaluation, the specificity of the propagated sequence features is
      estimated to be >99%, i.e. very few false positive predictions are made. MACSIMS
      is then used to characterise mutations in a test set of 100 proteins that are
      known to be involved in human genetic diseases. The number of sequence features
      associated with these proteins was increased by 60%, compared to the features
      available in the public databases. An XML format output file allows automatic
      parsing of the MACSIM results, while a graphical display using the JalView
      program allows manual analysis. CONCLUSION: MACSIMS is a new information
      management system that incorporates detailed analyses of protein families at the
      structural, functional and evolutionary levels. MACSIMS thus provides a unique
      environment that facilitates knowledge extraction and the presentation of the
      most pertinent information to the biologist. A web server and the source code are
      available at http://bips.u-strasbg.fr/MACSIMS/.

PMID- 16792822
TI  - When screening is still not enough.

PMID- 16792823
TI  - Our health, our care, our say.

PMID- 16792821
TI  - Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1 Tat protein
      basic domain into human chondrocytes.
AB  - This study was performed to investigate the transduction of a full-length
      superoxide dismutase (SOD) protein fused to transactivator of transcription (Tat)
      into human chondrocytes, and to determine the regulatory function of transduced
      Tat-SOD in the inflammatory cytokine induced catabolic pathway. The pTat-SOD
      expression vector was constructed to express the basic domain of HIV-1 Tat as a
      fusion protein with Cu, Zn-SOD. We also purified histidine-tagged SOD without an
      HIV-1 Tat and Tat-GFP as control proteins. Cartilage samples were obtained from
      patients with osteoarthritis (OA) and chondrocytes were cultured in both a
      monolayer and an explant. For the transduction of fusion proteins, cells/explants
      were treated with a variety of concentrations of fusion proteins. The transduced
      protein was detected by fluorescein labeling, western blotting and SOD activity
      assay. Effects of transduced Tat-SOD on the regulation of IL-1 induced nitric
      oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression
      was assessed by the Griess reaction and reverse transcriptase PCR, respectively.
      Tat-SOD was successfully delivered into both the monolayer and explant cultured
      chondrocytes, whereas the control SOD was not. The intracellular transduction of
      Tat-SOD into cultured chondrocytes was detected after 1 hours, and the amount of
      transduced protein did not change significantly after further incubation. SOD
      enzyme activity increased in a dose-dependent manner. NO production and iNOS mRNA
      expression, in response to IL-1 stimulation, was significantly down-regulated by
      pretreatment with Tat-SOD fusion proteins. This study shows that protein delivery
      employing the Tat-protein transduction domain is feasible as a therapeutic
      modality to regulate catabolic processes in cartilage. Construction of additional
      Tat-fusion proteins that can regulate cartilage metabolism favorably and
      application of this technology in in vivo models of arthritis are the subjects of
      future studies.

PMID- 16792824
TI  - NHS breast screening: a model national programme.

PMID- 16792825
TI  - Screening for breast cancer in England: past and future.
AB  - The NHS Breast Screening Programme (NHSBSP) began in 1988. It aims to invite all
      women aged 50-70 years for mammographic screening once every three years. The
      programme now screens 1.3 million women each year, about 75% of those invited,
      and diagnoses about 10,000 breast cancers annually. Although some have questioned
      the value of screening for breast cancer, the scientific evidence demonstrates
      clearly that regular mammographic screening between the ages of 50 and 70 years
      reduces mortality from the malignancy. Screened women are slightly more likely
      than unscreened women to be diagnosed with breast cancer. The cancers in screened
      women are smaller and are less likely to be treated with mastectomy than they
      would have been if diagnosed without screening. For every 400 women screened
      regularly by the NHSBSP over a 10-year period, one woman fewer will die from
      breast cancer than would have died without screening. The current NHSBSP saves an
      estimated 1400 lives each year in England. The screening programme spends about
      pound sterling 3000 for every year of life saved.

PMID- 16792827
TI  - Cervical screening in 20-24-year olds.
AB  - BACKGROUND: In 2003 the NHS Cervical Screening Programme in England changed the
      age at which women are first invited for cervical screening from 20 to 25 years.
      The aim of this review was to assess the evidence for benefit and harm of
      undertaking cervical screening in Wales for women aged 20-24 years. METHOD: A
      literature review looking for evidence of the effectiveness and potential harmful
      effects of cervical screening was undertaken. Welsh data for the number of cases
      of high-grade cervical intraepithelial neoplasia (CIN3) were examined and rates
      of invasive cervical cancer (1981-2003) for young women calculated. The medical
      notes of women less than 25 years old diagnosed with cervical cancer were
      reviewed and a cost analysis was performed. RESULTS: The literature review failed
      to identify any randomized controlled studies of the effectiveness of cervical
      screening in young women, but demonstrated that organized screening programmes
      result in a decrease in the incidence of cervical carcinoma. Following the
      introduction of the Welsh organized call/recall cervical screening programme in
      1988, cervical cancer has been reduced by 58% in women aged 20-24 years and 45%
      in women aged 25-29 years (mean age-specific rate per 100,000 women aged 20-24
      years: 4.2 in 1981-88 compared with 2.2 in 1989-2003). If these changes can be
      attributed to the screening of women aged 20-24, then the costs of at least pound
      sterling 82,500 are estimated to prevent one cervical cancer in this age group.
      CONCLUSIONS: The incidence of cervical cancer in young women has halved since the
      introduction of the Welsh-organized call-recall cervical screening programme. In
      Wales we recommend that women continue to be invited for cervical screening from
      20 years of age. This will provide the information required to compare the
      incidence and stage at diagnosis of cervical cancer in young women invited for
      first time cervical screening at different ages across the UK.

PMID- 16792828
TI  - The agreement between self-reported cervical smear abnormalities and screening
      programme records.
AB  - SETTING: The Million Women Study is a cohort study of women aged 50-64 years in
      England and Scotland. As a component of the follow-up questionnaire, participants
      were asked to indicate if they had an abnormal cervical smear in the previous
      five years. This study compared self-reported cervical abnormalities with
      screening records obtained from the National Health Service Cervical Screening
      Programme. METHODS: For 1944 randomly selected Million Women Study participants
      in Oxfordshire, screening records were assessed over a six-year period prior to
      the date of self-reporting. The six-year period was chosen to allow for errors in
      the recall of timing of abnormal smears. RESULTS: A total of 68 women (3.5%) had
      a record of at least one equivocal or abnormal smear within the last six years,
      whereas 49 women (2.5%) self-reported an abnormality. There was a strong trend
      for an increased probability of self-reporting a history of an abnormal smear as
      the severity of the recorded abnormality increased (P <0.001). For women with an
      NHS record of borderline dyskaryosis, mild dyskaryosis, or moderate
      dyskaryosis/severe dyskaryosis/invasive cancer, the proportions reporting an
      abnormality were 40%, 58% and 77%, respectively. For women with negative and
      inadequate smears, the proportion self-reporting an abnormality were 0.6% and
      0.7%, respectively. CONCLUSIONS: These results indicate that among women whose
      screening programme records show an abnormal smear, the proportion self-reporting
      an abnormality increases with the severity of the recorded lesion. Almost all
      women with a record of negative or inadequate smear(s) correctly interpret the
      result and do not self-report an abnormality.

PMID- 16792829
TI  - Neonatal haemoglobinopathy screening: review of a 10-year programme in Brussels.
AB  - Since 1994, a neonatal screening programme for major haemoglobinopathies has been
      conducted in Brussels. We performed a 10-year re-evaluation of the incidence of
      haemoglobinopathies in Brussels and found that of the 118,366 newborns screened,
      64 were diagnosed with a sickle cell syndrome, six had beta-thalassaemia major,
      four had a haemoglobin C disease and three had a haemoglobin H disease. Of the 64
      babies with a sickle cell disease, two died before the age of two years and two
      did not present at the first neonatal visit. Of the six babies suffering from
      beta-thalassaemia major, all are alive and two have undergone a haematopoietic
      stem cell transplantation. The universal neonatal screening programme for
      haemoglobinopathies should be maintained in Brussels.

PMID- 16792830
TI  - Development and characterization of dried blood spot materials for the
      measurement of immunoreactive trypsinogen.
AB  - OBJECTIVES: In response to increasing numbers of states in the US that test
      newborn babies for cystic fibrosis (CF), the Newborn Screening Quality Assurance
      Programme initiated a pilot proficiency testing programme for immunoreactive
      trypsinogen (IRT), the biomarker for CF. Dried blood spot specimens (DBS) were
      used to evaluate the performance of laboratories that screen babies for CF.
      METHODS: DBS were prepared from human whole blood enriched with physiologically
      relevant levels of IRT. Various methods of making IRT-enriched DBS were used to
      optimize the recovery and stability of the biomarker, including preparation of
      DBS from either intact or lysed red blood cells, varying the timing of IRT
      addition to blood before dispensing onto filter paper, adding a protease
      inhibitor cocktail, and treating serum with charcoal before IRT enrichment. The
      recovery and stability of IRT in DBS were assessed. Newborn screening
      laboratories were offered the opportunity to test blind-coded DBS in the pilot PT
      programme. RESULTS: IRT was stable in the filter paper matrix when stored for one
      year at either -20 degrees C or 4 degrees C. Fifty percent more IRT was recovered
      from DBS prepared with lysed red blood cells where the IRT was added to blood
      just before dispensing; however, protease inhibitors did not improve IRT
      recovery. CONCLUSIONS: IRT in the DBS matrix is stable and can be shipped
      worldwide under ambient conditions. Optimal IRT recovery was achieved by
      adjustment of DBS production practices. Laboratories receiving specimens
      accurately measured IRT by a variety of commercial and in-house methods.

PMID- 16792831
TI  - Prevalence of G6PD deficiency in newborns in the south of Brazil.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder which
      causes neonatal jaundice in most cases, and in association with intake of drugs
      or certain foods (for example fava) can cause haemolytic crises. The aim of this
      study was to determine the prevalence of G6PD deficiency in Rio Grande do Sul
      (RS), the southernmost state of Brazil. We tested 2799 newborn blood samples. A
      commercial kit was used for the quantitative measurement of G6PD activity. Of the
      2799 samples, 39 (1.4%) exhibited total deficiency, 178 (6.4%) exhibited
      intermediate deficiency and 2582 (92.2%) were normal. We found no correlation
      between G6PD deficiency and ethnic origin, but a high prevalence of patients with
      partial deficiency could be associated with the type of colonization of RS. The
      combined prevalence for both types of deficiency (complete and partial) was 7.9%
      among the newborn population. This finding is important as both types of
      deficiency must receive same kind of preventive care.

PMID- 16792832
TI  - Towards comprehensive population-based screening for diabetic retinopathy:
      operation of the North Wales diabetic retinopathy screening programme using a
      central patient register and various screening methods.
AB  - OBJECTIVES: To examine whether population-based retinopathy screening using a
      central diabetes register and employing various screening methods can achieve a
      high degree of population coverage to meet National Screening Committee (NSC)
      targets. To identify the main barriers to achieving comprehensive population
      coverage. To analyse referrals to ophthalmology and their outcome as a measure of
      previously unmet need. To assess the influence of modality of screening. SETTING:
      Three local health board areas in North Wales. METHODS: Establishment of a
      district diabetes register to hold records of all patients and subserve call
      recall of general practitioner (GP) sole-care patients for screening by
      optometrists or digital photography. Hospital attenders were screened in diabetic
      clinic by direct ophthalmoscopy. Data were collected for years 1 and 2 of
      operation of the scheme. RESULTS: The system held a screening record for 86% of
      diabetic patients after year 1 and 93% after year 2. Failure to attend was the
      major barrier to comprehensive population screening, but this improved in year 2
      (P<0.001). Both optometrists and photography identified substantial unmet need:
      1% of all GP sole-care patients required immediate laser treatment. Photography
      was more sensitive than optometrist screening, but the additional retinopathy
      identified was mostly minor not requiring treatment. CONCLUSIONS: Lack of
      screening is much more important than modality of screening as a cause of missed
      sight-threatening retinopathy. A central, district-based patient register system
      identifies those patients not screened for further follow-up and can produce a
      high level of population coverage, close to NSC targets. Such schemes are needed,
      particularly to support primary care diabetes management.

PMID- 16792833
TI  - Hormone replacement therapy and mammographic screening outcomes in Western
      Australia.
AB  - OBJECTIVES: The study objectives were three-fold: to estimate the effect of
      hormone replacement therapy (HRT) use on the sensitivity of mammographic
      screening; to examine the odds of having an interval cancer as a function of
      duration of HRT use and to compare the size, grade, lymph node and hormone
      receptor status of tumours for HRT users and non-users. SETTING: Perth, Western
      Australia, where a free, population-based mammographic screening service targets
      women aged 50-69 years. METHODS: The cohort consisted of 113,310 women who had
      119,296 screening episodes between January 1998 and December 1999. Unconditional
      logistic regression was used to model the odds of having an interval cancer as a
      function of the effect of the duration of HRT use (measured in years). Using
      subsequent screening rounds, chi2-tests were used to examine whether HRT users
      differed from HRT non-users in terms of tumour characteristics. RESULTS: Ninety
      seven screen-detected and 31 interval cancers were diagnosed among women who were
      on initial screening rounds, and 393 screen-detected and 153 interval cancers
      were diagnosed among women on subsequent screens, two years post screening. Two
      year sensitivity outcomes were significantly lower for HRT users on initial
      screening rounds. For women on subsequent screening rounds, the odds of having an
      interval cancer increased with the duration of HRT use (odds ratio 1.09, 95%
      confidence interval 1.04-1.14, P<0.04) after controlling for age, family history,
      tumour grade, size and pathology type. The histopathological characteristics of
      cancers did not differ for HRT users compared with HRT non-users. CONCLUSION: The
      sensitivity of mammographic screening was reduced and the odds of having an
      interval cancer were increased for HRT users compared with HRT non-users. For
      women on subsequent screening episodes, the odds of having an interval cancer
      increased with duration of HRT use.

PMID- 16792834
TI  - Prognostic importance of palpability as a feature of screen-detected breast
      cancers.
AB  - OBJECTIVES: To determine epidemiological characteristics of palpability as a
      feature of asymptomatic invasive breast cancers detected through screening
      mammography, and to determine whether palpability is predictive of case survival
      after adjusting for conventional prognostic indicators such as diameter, grade
      and nodal status. SETTING: The University of Adelaide, South Australian
      Department of Health, and The Cancer Council South Australia, Adelaide, South
      Australia. METHODS: Sociodemographic and clinical characteristics of 2108 screen
      detected invasive breast cancers were compared by tumour palpability using
      univariate and multiple logistic regression analysis. Survival outcomes from
      breast cancer were compared using Kaplan-Meier product-limit estimates.
      Multivariable proportional hazard regression was employed to assess the
      association of palpability with survival after adjusting for conventional
      prognostic indicators. RESULTS: Palpability was associated with year of
      diagnosis, ductal histology type, and unfavourable prognostic indicators such as
      larger tumour diameter, higher grade and nodal involvement. After adjusting for
      these variables, no associations were found with age at diagnosis, place of
      residence or socioeconomic status, or with presence of multifocal disease or
      presence of an extensive in situ component. Palpability was predictive of death
      from breast cancer in an unadjusted analysis, the relative risk (95% confidence
      limits) being 1.75 (1.12, 2.74). After adjusting for nodal involvement and larger
      tumour size, the relative risk no longer was elevated, reducing to 0.99 (0.60,
      1.64). DISCUSSION: Palpability is associated with unfavourable prognostic
      indicators, such as larger diameter, higher grade and nodal involvement, and is
      not an independent indicator of survival outcome for screen-detected female
      breast cancers after accounting for nodal involvement and diameter.

PMID- 16792835
TI  - Receiver operating characteristics of the prostate specific antigen test in an
      unselected population.
AB  - OBJECTIVES: To determine the operating characteristics of prostate-specific
      antigen (PSA) testing and prostate cancer diagnosis rates in men who have had an
      initial PSA test in Tayside. SETTING: A retrospective cohort study in Tayside,
      Scotland from 1992 to 2001. METHODS: In total, 20,623 men were PSA tested during
      the period 1992-2001. After exclusions, 19,660 were studied. Sensitivity and
      specificity were calculated for various PSA cut-off values by age group using
      logistic regression weighted for verification bias (biopsy). Cox regression
      analysis was performed using six test pattern cohorts. RESULTS: The annual rate
      of PSA testing increased from 5.1 per 1000 man years in 1992 to 21.3 per 1000 man
      years in 2001. The average number of PSA tests per patient increased from 1.11 in
      1992 to 2.57 in 2001. Prostate cancer diagnosis and death rates remained constant
      from 1995 onward. The PSA test had generally inadequate sensitivity and
      specificity values, so a unique cut-off could not be found for the two older age
      groups which could be used as a recommendation for biopsy. The commonly used 4
      ng/mL cut-off was reasonably sensitive and specific only for the under 60 age
      group with values of 92.4% and 90.7%, respectively. For prostate cancer
      diagnosis, the hazard ratios (HR) were reported relative to those with a series
      of all normal tests. For those with an initially normal PSA test who had at least
      one abnormal retest result the HR for diagnosis was 10.43 (95% confidence
      interval [CI] 6.17-17.63). For those with initially abnormal tests with normal
      retests HR = 1.63 (95% CI 0.65-4.07). CONCLUSIONS: There are no optimal PSA cut
      off values for older age groups with which to make a confident referral for
      biopsy. The increase in PSA testing and the questionable cut-off values of the
      test calls for the development of an alternative screening strategy.

PMID- 16792836
TI  - A complete trisomy 9 associated with abnormal triple screening result.

PMID- 16792838
TI  - An appeal for statistical rigour.
AB  - Following recent comments by Jean Cohen in this journal, this short note is yet
      another appeal for a higher standard of statistical analysis in Assisted
      Reproduction Research. In order to avoid the conflicts and contradictions
      highlighted by Jean Cohen, it is imperative that the highest standards of
      numerical evaluation are maintained. To this end, research workers are urged to
      recruit statisticians to assist in the analysis and interpretation of their
      results, and in the preparation of their manuscripts. Statistical science is held
      in rather low esteem in many quarters, a situation that is aggravated by the
      publicity attached to contradictory findings. A higher standard of statistical
      analysis is required to restore the subject's standing among research workers.

PMID- 16792839
TI  - Delayed motherhood through oocyte and ovarian tissue cryopreservation - a
      perspective from Singapore.
AB  - Recent advances in oocyte and ovarian tissue cryopreservation technology have
      brought hope not only to women facing premature loss of ovarian function, but
      also to healthy women seeking delayed motherhood. This is a major issue of
      contention in healthcare ethics. Proponents of this new technology argue that
      this enables women to pursue educational and career goals in their youth, so that
      they have greater financial security for children in later life. Nevertheless,
      this argument may be flawed by the reality that even if the cryopreservation of
      oocytes and ovarian tissue were optimized in the future, this would in no way be
      a guaranteed route for women to have biological children later in life. Moreover,
      because only a limited amount of autologous reproductive material can be
      cryopreserved and stored for a single healthy woman, there is a risk of material
      depletion before reproductive success is attained. Another prime consideration is
      the increased morbidity and mortality associated with clinical assisted
      reproduction in older women. Hence, it is imperative that delayed motherhood
      through the cryopreservation of oocytes and ovarian tissues be viewed with
      extreme caution, and mandatory counselling should be given to all patients if
      such a medical procedure ultimately finds approval for widespread application.

PMID- 16792840
TI  - Improving the consistency of ovarian stimulation: follitropin alfa filled-by
      mass.
AB  - In their quest for a child, infertile couples embark on a journey that is full of
      expectations and hopes. Over recent years, treatment procedures for assisted
      conception have become safer and more efficient. However, couples undergoing
      treatment can still experience some degree of emotional stress due to
      disappointment if pregnancy is not achieved, or if treatment cycles may have to
      be cancelled due to a low- or hyper-response. Strategies aimed at minimizing the
      variability of ovarian response or overall treatment outcome can be expected to
      significantly reduce this emotional stress. New developments have led to the
      production of follitropin alfa filled by mass. This is a highly consistent FSH
      preparation improving the consistency of ovarian response and reducing the risk
      of cycle cancellation. The impact of this new FSH preparation for assisted
      reproduction treatments is discussed in this review.

PMID- 16792841
TI  - Effects of metformin on inappropriate LH release in women with polycystic ovarian
      syndrome and insulin resistance.
AB  - The role of hyperinsulinaemia in neuroendocrine abnormalities in polycystic
      ovarian syndrome (PCOS) is controversial. The present study applied frequent
      blood sampling to assess the response of LH to metformin treatment in insulin
      resistant women with PCOS. Thirteen predominantly overweight women with PCOS were
      studied before and after treatment with 1.5 g/day metformin for 3 months. Serum
      LH and testosterone were measured every 10 min for 10 h; LH was measured for an
      additional 2 h after gonadotrophin-releasing hormone (GnRH) administration. LH
      pulses were characterized by cluster analysis, secretory LH episodes by a
      deconvolution procedure, and synchronicity of paired LH-testosterone
      concentrations by lag-specific cross-correlation. After treatment, basal LH
      concentrations, amplitude of LH pulses, LH secretory amplitude, response to
      exogenous GnRH, and basal testosterone concentrations significantly decreased in
      seven patients, whereas in the remaining women these parameters remained
      unaltered. Before treatment, decreased coordinate LH and testosterone release was
      manifested by all patients; metformin treatment led to re-establishment of the
      feed-back control of testosterone on LH secretory rates by -20 to 0 min.
      Treatment did not modify the glucose:insulin ratio or serum insulin
      concentrations. In conclusion, administration of metformin allowed the
      identification of two subsets of PCOS women in whom neuroendocrine abnormalities
      may improve independently of the presence of insulin resistance or
      hyperinsulinaemia.

PMID- 16792842
TI  - Mutual creativity of tissue engineering and gene therapy.

PMID- 16792843
TI  - FSH and folliculogenesis: from physiology to ovarian stimulation.
AB  - FSH is a glycoprotein hormone consisting of two peptide subunits. The role of FSH
      in folliculogenesis is well known: to stimulate the formation of a large pre
      ovulatory follicle that, because of its FSH-dependent maturation, is capable of
      ovulation and forming a corpus luteum in response to the mid-cycle surge of LH.
      FSH is widely used in ovarian stimulation for assisted reproduction techniques.
      Ovarian stimulation protocols combine the use of human menopausal gonadotrophin,
      urinary FSH or recombinant FSH with gonadotrophin-releasing hormone (GnRH)
      agonists or antagonists in order to increase oocyte number and to avoid premature
      LH surge. Recently, the availability of recombinant LH has permitted new
      stimulation protocols, combining recombinant FSH, recombinant LH and GnRH
      antagonists. Due to the limitations of the new Italian law in terms of the number
      of oocytes that can be fertilized, protocols with a softer ovarian stimulation
      are now considered, reducing risk of ovarian hyperstimulation syndrome, multiple
      pregnancies and emotional and physical burdens on the patients. Long-acting FSH
      preparations are also under clinical study. Knowledge of the stereochemical three
      dimensional structure of FSH and its receptor will allow the study of new non
      peptide orally administered molecules that fit the FSH receptors.

PMID- 16792844
TI  - Anti-Mullerian hormone: clinical insights into a promising biomarker of ovarian
      follicular status.
AB  - In contrast to most hormonal biomarkers of the follicular status, anti-Mullerian
      hormone (AMH) is exclusively produced by the granulosa cells of a wide range of
      follicles (primary to the early antral stages), presumably FSH-independently and
      with little susceptibility to disorders of antral follicle growth during the
      luteal-follicular transition. This paper summarizes the authors' clinical
      research on the role of AMH as a marker of ovarian functioning. It shows that the
      relationship between antral follicle counts and serum AMH concentrations is
      stronger than that observed with FSH, inhibin B and oestradiol on day 3, and that
      intercycle reproducibility of AMH measurements is better than the latter
      parameters. In addition, peripheral AMH concentrations decline during ovarian
      stimulation, thus confirming that maturing follicles loose progressively their
      ability to produce AMH. Indeed, follicular fluid (FF) AMH concentrations in small
      antral follicles are 3-fold as high as AMH in pre-ovulatory follicles. Further,
      human chorionic gonadotrophin-driven luteinization additionally curtails
      follicular AMH production. Finally, AMH production measured in FF from individual
      follicles is increased in women having normal follicular counts and
      responsiveness to ovarian stimulation. Together, these data reinforce the
      soundness of AMH measurements as a quantitative and possibly qualitative marker
      of granulosa cell activity and health.

PMID- 16792845
TI  - Medical treatment to improve sperm quality.
AB  - Approximately 30% of cases of couple infertility are due to a male factor.
      Several conditions can interfere with spermatogenesis and reduce sperm quality
      and production. Treatable conditions, such as hypogonadism, varicocele,
      infections and obstructions, should be diagnosed and corrected, but many aspects
      of male factor infertility remain unclear. Various agents have been used in the
      attempt to increase the fertility potential of subjects with idiopathic
      oligoteratoasthenozoospermia. The rationale of medical treatment to improve sperm
      quality in these subjects has been questioned by the introduction of assisted
      reproductive technologies. However, there is now growing awareness of the
      importance of good quality spermatozoa for embryonic development and higher birth
      rates. Confounding factors in assessing the efficacy of male infertility
      treatments have erroneously inflated the superiority of assisted reproductive
      technologies over conventional approaches. A systematic review is given of
      relevant randomized controlled trials and effects on semen parameters. The
      analysis reveals that although results are heterogeneous, gonadotrophins, anti
      oestrogens, carnitine and trace elements may be beneficial in improving sperm
      quality, although their effect on pregnancy rate remains controversial. The most
      common drug regimens are compared and an estimate of the results expected from
      these treatments provided.

PMID- 16792846
TI  - Epiblast and primitive endoderm segregate in murine blastocysts.

PMID- 16792847
TI  - Sperm nuclear DNA damage: update on the mechanism, diagnosis and treatment.
AB  - Previous studies have shown that repeated intracytoplasmic sperm injection
      failures can be associated with sperm DNA damage. This paper reviews the current
      understanding of the mechanism of sperm DNA damage, discusses different
      diagnostic methods and their threshold values to discriminate between good- and
      poor-prognosis patients, and outlines the currently available treatment options.
      A rational approach to the interpretation of sperm DNA fragmentation data and to
      the choice of the optimal treatment method is suggested.

PMID- 16792848
TI  - Adjuvant therapy enhances endometrial receptivity in patients undergoing assisted
      reproduction.
AB  - Adjuvant therapies are often used to enhance endometrial thickness during IVF.
      This retrospective cohort analysis investigated if women undergoing oocyte
      donation cycles with sonographic evidence of endometrial insufficiency benefit
      from adjuvant medicaltherapy. Infertile patients received 503 mock cycles
      followed by 503 anonymous oocyte donation cycles. One hundred and twenty-three
      patients received adjuvant therapy during a donor oocyte cycle. Patients who had
      a mock endometrial thickness > or = 8 mm experienced a significant decrease in
      endometrial thickness with the donor oocyte cycle regardless of the use of
      adjuvant therapy (P < 0.001). In contrast, those patients with a mock endometrial
      thickness < 8 mm experienced a significant increase in donor oocyte cycle
      endometrial thickness regardless of adjuvant therapy use (P < 0.001). The
      patients with a mock endometrial thickness < 8 mm experienced a significant
      improvement in pregnancy rates when taking adjuvant therapy (87.7 versus 73.5%, P
      < 0.05). Adjuvant therapy significantly improved both pregnancy (87.8 versus
      76.8%, P < 0.01) and live birth rates (74.8 versus 63.7%, P < 0.05) in the entire
      patient population. While the use of adjuvant therapy did not significantly
      improve ultrasonographic endometrial thickness, it did improve outcome rates.

PMID- 16792849
TI  - Comparison of in-vitro outcomes from cryopreserved oocytes and sibling fresh
      oocytes.
AB  - In Italy, the restrictive IVF law generalizes the indication for oocyte freezing
      for surplus oocytes in 78.5% of in-vitro assisted reproductive cycles. With a
      view to understanding better what the prospects for intracytoplasmic sperm
      injection (ICSI) on frozen-thawed oocytes might be, the consequences of freeze
      thaw procedures on fertilization, cleavage rates and embryo quality obtained from
      frozen-thawed oocytes were studied and compared with the results obtained from
      sibling fresh oocytes. Eleven IVF and 29 ICSI on 76 and 169 fresh oocytes were
      performed and the corresponding 40 ICSI on 221 sibling frozen-thawed oocytes.
      There was no difference in terms of fertilization rate between fresh and sibling
      frozen-thawed oocytes. The cleavage rate (98.0 and 94.4% with fresh oocytes in
      IVF and ICSI; 77.3% with frozen-thawed oocytes in ICSI; P < 0.001) and embryo
      quality (grade I embryos over total embryos: 36.7 and 22.2% with fresh oocytes in
      IVF and ICSI; 12.1% with frozen-thawed oocytes in ICSI; respectively P < 0.001
      and P < 0.05) were statistically lower after oocyte cryopreservation. The
      significant decrease in meiotic spindle retrieval rate before freezing (62.4%)
      and after thawing procedures (43.4%; P < 0.001) suggests that cryoconservation
      induces irreversible damage to microtubule repolymerization. The consequences of
      oocyte cryopreservation procedures on embryo development are reviewed.

PMID- 16792850
TI  - Milk as an essential factor in pregnancy.

PMID- 16792851
TI  - Light retardance by human oocyte spindle is positively related to pronuclear
      score after ICSI.
AB  - Disturbed spindle assembly increases risks of chromosome mal-segregation. Non
      invasive polarization microscopy (PolScope) was employed in two centres to assess
      spindle integrity for the first time quantitatively in human oocytes from
      consenting patients undergoing intracytoplasmic sperm injection (ICSI) with
      respect to pronuclear (PN) score after fertilization. In one centre oocytes were
      selected before ICSI, in another selection was after ICSI according to PN score.
      In both centres, mean retardance of light by birefringent spindles in oocytes
      forming a pre-embryo with good PN score after ICSI was significantly higher
      compared with spindles in oocytes developing into a lower PN score pre-embryo
      with limited developmental potential (P < 0.001). Transfers involving oocytes
      with high retardance and at least one good PN score embryo resulted more
      frequently in a conception than transfers from oocytes with spindles of lower
      mean retardance and lower PN score embryos. There was a trend for an inverse
      relationship between age and magnitude of retardance in a small oocyte cohort.
      The study suggests that quantitative evaluation of mean retardance of light by
      the oocyte spindle predicts oocyte health, is related to PN score of the embryo
      and may be especially useful to assess oocyte quality in countries with legal
      restrictions to select after fertilization.

PMID- 16792852
TI  - Trophectodermal markers in cleaving embryos.

PMID- 16792853
TI  - Preliminary FISH studies on spermatozoa and embryos in patients with variable
      degrees of teratozoospermia and a history of poor prognosis.
AB  - The aim of this study was to analyse to what extent sperm aneuploidy is
      associated with sperm morphology and subsequently with embryo aneuploidy. Fifty
      nine men with variable degrees of teratozoospermia and previously poor assisted
      reproduction prognosis were included in the study. Samples from 10
      normozoospermic men with proven fertility were used as controls. Individual
      spermatozoa were scored for chromosomes 13, 21 and for 18, X, Y separately.
      Compared with controls, 23 out of 59 cases (39.0%) were found to have increased
      sperm aneuploidy for at least one of the chromosomes analysed in a treatment
      cycle. Fifty-two patients underwent a treatment cycle and were documented
      according to the pregnancy and spermatozoa fluorescence in-situ hybridization
      results. A total of 121 previous unsuccessful assisted reproduction cycles of the
      cases were then retrospectively reviewed. In 23 of the latest cycles,
      preimplantation genetic diagnosis was applied to 106 cleavage stage embryos and
      47 of 94 embryos analysed (50.0%) were found to be chromosomally abnormal.
      Furthermore, 16 of 47 (34.0%) embryos with chromosomal abnormality were carrying
      complex chromosomal defects. The results imply that increased aneuploidy is
      present in both spermatozoa and embryos in couples with severe male infertility
      with a history of repeated unsuccessful attempts. Therefore, proper genetic
      counselling should be considered in these cases.

PMID- 16792854
TI  - Mitochondrial markers in human haemopoietic cells.

PMID- 16792855
TI  - On the way to reprogramming cells to pluripotency using cell-free extracts.
AB  - The functional reprogramming of a differentiated cell to pluripotency may present
      beneficial applications in regenerative medicine. Somatic cell nuclear transfer
      may offer this possibility, but technical hurdles and ethical guidelines
      currently prevent application of this technology in several countries. As a
      result, alternative approaches are being developed for altering cell fate. Recent
      non-nuclear transfer-based approaches for reprogramming somatic cells are
      discussed as well as ways to enhance their differentiation potential. These
      approaches include the fusion of differentiated cells with embryonic stem cells
      and the use of extract from pluripotent cells to reprogramme differentiated cells
      into multipotent or pluripotent cells.

PMID- 16792856
TI  - An approach to the ethical donation of human embryos for harvest of stem cells.
AB  - This paper considers embryo grading within a given infertility treatment and
      suggests an ethical approach to embryo donation for embryonic stem cell harvest.
      It is concluded that ethical considerations regarding human embryos do not
      necessarily preclude the use of certain embryos for biomedical research or
      transplantation. The argument is based on the following rationale: all embryos
      are not physiologically equal, some low-grade embryos will never be chosen for
      implantation, cells from low-grade embryos may be donated for transplantation or
      research, and embryonic stem cells can be harvested from low-grade embryos. This
      argument bears special importance at this time as embryos created by IVF are
      still the only source of embryonic stem cells, given the current controversy
      surrounding published studies of human somatic cell nuclear transfer.

PMID- 16792857
TI  - Omental and peritoneal secondary trophoblastic implantation - an unusual
      complication after IVF.
AB  - Omental pregnancy is an uncommon form of abdominal pregnancy; it has never been
      previously reported after IVF. A 35-year-old patient underwent IVF for tubal
      factor infertility. The treatment cycle was uneventful, but 3 weeks following
      embryo transfer the patient was diagnosed with a right tubal ectopic pregnancy on
      ultrasound. A laparoscopic salpingectomy was performed and the patient was
      discharged home. Two weeks later, the patient presented with abdominal pain and
      rising serum beta-human chorionic gonadotrophin (beta-HCG). A repeat laparoscopy
      showed omental and peritoneal trophoblastic implants. These were excised
      laparoscopically and confirmed on histology to be trophoblastic tissue. The HCG
      returned to < 3 IU/l, 1 week post-operatively. This case emphasizes the
      importance of intra-operative care during laparoscopic surgery for ectopic
      pregnancy and the need for post-operative surveillance of serum beta-HCG. An
      abdominal pregnancy, though rare, has a seven times higher mortality rate than
      non-abdominal pregnancies. Early diagnosis and treatment can prevent intra
      abdominal haemorrhage, as haemorrhagic shock is the commonest cause of mortality
      from omental pregnancy.

PMID- 16792858
TI  - Are programmable freezers still needed in the embryo laboratory? Review on
      vitrification.
AB  - The predictable answer to the provocative question of whether programmable
      freezers are still needed in the embryo laboratory is an even more provocative
      'no'. However, such a radical statement needs strong support. Based on the
      extensive literature of the past 5 years, the authors collected arguments either
      supporting or contradicting their opinion. After an overview of the causes of
      cryoinjuries and strategies to eliminate them, the evolution of vitrification
      methods is discussed. Special attention is paid to the biosafety issues. The
      authors did not find any circumstance in oocyte or embryo cryopreservation where
      slow freezing offers considerable advantages compared with vitrification. In
      contrast, the overwhelming majority of published data prove that the latest
      vitrification methods are more efficient and reliable than any version of slow
      freezing. Application of the proper vitrification methods increases the
      efficiency of long-term storage of stem cells and opens new perspectives in
      cryopreservation of oocytes, both for IVF and somatic cell nuclear transfer.
      However, lack of support from regulatory authorities, and conservative approachs
      regarding novel techniques can slow down the implementation of vitrification. The
      opinion of the authors is that vitrification is the future of cryopreservation.
      The public have the final say in whether they want and allow this future to
      arrive.

PMID- 16792859
TI  - Claims to frozen embryos rejected.

PMID- 16792860
TI  - [To evaluate treatments of chronic hepatitis B].

PMID- 16792861
TI  - [Immune adjuvant effect of TB.HSP70 to its accompanying cytotoxic T lymphocytes
      epitope elicits HBV specific immune response].
AB  - OBJECTIVE: To investigate whether Mycobacterium tuberculosis heat shock protein
      70 (TB.HSP70) can be used as an adjuvant carrier to stimulate immune response to
      an accompanying cytotoxic T lymphocytes (CTL) epitope peptide from hepatitis B
      virus (HBV) core antigen. METHODS: In vitro, peripheral blood mononuclear cells
      (PBMCs) from chronic hepatitis B volunteers were stimulated with TB.HSP70-CTL
      fusion protein and TB.HSP70/CTL complex, and then HBV specific CTL activity was
      assessed. In vivo, the CD4+ T, CD8+ T and natural killer cells (NKs) in the
      peripheral blood and in spleens of the immunized mice were measured by flow
      cytometry and the protective HBV specific immune responses of the mice were also
      evaluated. RESULTS: The results revealed that both of them could induce HBV
      specific CTL response in human PBMCs and in the immunized mice. In the mice they
      activated CD4+ T, CD8+ T and NKs. Furthermore, the immunocompetence of the
      TB.HSP70-CTL fusion protein was stronger than that of TB.HSP70/CTL complex. The
      HBV specific killing rate was 28.9%, the CD8+ T cell population was 43.9% and the
      NKs was 13.6% in splenocytes of immunized mice with TB.HSP70-CTL fusion protein.
      The CTL peptide alone was capable of generating weak CTL lysis. The TB.HSP70
      showed almost no target cell killing. CONCLUSION: The results demonstrate that
      TB.HSP70 may be used as a new adjuvant carrier to improve the immunogenicity of
      short CTL epitope and produce effective CTL response.

PMID- 16792862
TI  - [The impact of HBeAg positivity/negativity and HBV DNA loads on the prognosis of
      chronic severe hepatitis B].
AB  - OBJECTIVE: To explore the impact of HBeAg positivity/negativity and HBV DNA loads
      on the prognosis of chronic severe hepatitis B. METHODS: 206 patients with
      chronic severe hepatitis B hospitalized in Beijing Ditan Hospital from July 2002
      to Dec. 2004 were analyzed. HBeAg positivity/negativity, HBV DNA loads and other
      factors relating to the prognosis of the patients were studied with univariate
      and multivariate analyses. RESULTS: Chi2 univariate analysis showed that there
      was no significant difference in the prognosis between different HBeAg groups
      (chi2 = 0.440, OR = 0.777, 95% CI 0.424-1.425, P = 0.50). But there was a
      significant difference in the prognosis between different HBV DNA load groups:
      the prognosis of patients with lower HBV DNA loads was better than those with
      higher loads (chi2 = 9.806, OR = 3.055, 95% CI 1.554-6.007, P = 0.002), and the
      improving rates of the two groups were 53.1% and 27.0% respectively. Using
      multivariate logistic regression analysis, 9 screened factors showed great impact
      on the prognosis of chronic severe hepatitis B. Cirrhosis, hepatorenal syndrome,
      hepatic encephalopathy, PTA < 20%, TBil > 513 mmol/L, Alb < 30 g/L, CHO < 1.6
      mmol/L, PLT < 5 x 10(9)/L, and higher HBV DNA loads (HBV DNA > 3 x 10(4)
      copies/ml in HBeAg negative patients and > 1 x 10(5) copies/ml in HBeAg positive
      patients) were shown to be associated with a poor prognosis. Coefficients of
      regression of the above factors were 1.539, 21.356, 1.398, 1.650, 2.440, 2.266,
      1.738, 2.631 and 2.656 respectively. The coefficients of regression of HBV DNA
      loads were: B = 2.656, Wald = 7.768, P = 0.005, EXP(B) = 14.235, and 95.0% CI for
      EXP(B) = 2.199-92.133. CONCLUSIONS: Our results indicate that the HBV DNA loads
      were one of the most important factors influencing the prognosis of the chronic
      severe hepatitis B patients, the importance is only next to hepatorenal syndrome
      and over grade II hepatic encephalopathy. HBeAg positivity/negativity has no
      influence on the prognosis, but HBV DNA loads are important; the lower the viral
      loads, the better the prognosis.

PMID- 16792863
TI  - [Hepatitis C virus NS5A protein upregulates survivin gene expression].
AB  - OBJECTIVE: To investigate whether the nonstructural protein 5A (NS5A) encoded by
      the human hepatitis C virus RNA genome could affect the expression of the
      survivin gene. METHODS: HCV NS5A expression plasmid (pCNS5A) was transfected into
      HepG2 cells using a lipofectin reagent and the HCV NS5A protein was detected
      using immuno-histochemistry staining. Survivin mRNA was evaluated by reverse
      transcriptase polymerase chain reaction (RT-PCR) and the expression of survivin
      protein was detected using Western blot. RESULTS: HCV NS5A protein was detected
      in the cytoplasm of the HepG2 cells transfected with pCNS5A, and the expressions
      of survivin mRNA and survivin protein were both up-regulated in the presence of
      the HCV NS5A protein. CONCLUSIONS: HCV NS5A protein can stimulate survivin
      protein expression, and this might be the result of the strengthening of the
      survivin gene transcription.

PMID- 16792864
TI  - [MxA gene-88 G/T polymorphism influences the outcomes of HBV infection].
AB  - OBJECTIVE: To study the relationship between a G/T substitution at position -88
      of myxovirus resistance-1 gene (MxA) and the self-limiting or chronic infection
      of HBV. METHODS: Blood samples from 100 patients with self-limiting HBV infection
      (positive anti-HBs and anti-HBc) and from 340 patients with chronic HBV infection
      were collected. MxA-88 G/T polymorphism was typed using a protocol based on
      competitively differentiated-polymerase chain reaction. For statistical analysis,
      odds ratio and chi-square test were used. RESULTS: The detective rate of G/G
      genotype (low expression genotype) of MxA-88 G/T was 50.2% (221/440), those of
      T/T genotype (high expression genotype) and G/T heterozygous genotype were 5.5%
      (24/440) and 44.3% (195/440). Compared to patients with chronic infection,
      patients with self-limiting infection had lower frequency of G/G genotype (41.0%
      vs 52.9%, P < 0.05) or G allele (62.5% vs 75.9%, P < 0.01) and had higher
      frequency of T/T genotype (16.0% vs 2.4%, P < 0.01) or T allele (37.5% vs 24.1%,
      P < 0.01), but there was no significant difference in the G/T heterozygous
      genotype. CONCLUSIONS: MxA gene -88 G/T polymorphism influences the natural
      outcomes of HBV infection to some extent. This SNP of MxA gene may be used as a
      clinical prognostic marker of HBV infection.

PMID- 16792865
TI  - [The effect of Fuzheng Huayu Decoction on the hepatic proteome during the
      formation and resolution of rat liver fibrosis].
AB  - OBJECTIVE: To investigate the dynamic changes of the hepatic proteome during the
      formation and resolution of rat liver fibrosis induced by carbon tetrachloride
      and the effect of Fuzheng Huayu Decoction on it. METHODS: Liver fibrosis in
      Wistar rats was induced by subcutaneous injection of 40% CCl4 in olive oil while
      the rats in the treatment group received Fuzheng Huayu Decoction. Pathological
      examination, hydroxyproline content determination and protein extraction of the
      rats livers were performed at four time points, i.e. at the end of 4, 8, 12 and
      16 weeks. After 2-dimensional electrophoresis (2-DE), the gels were analyzed
      using the PDQUEST 2-DE image analysis software and differentially expressed
      proteins were identified using matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: (1) The 2-DE examination
      showed that the model group-specific proteins and differentially expressed
      proteins presented started at 4 weeks and reached their peaks at 12 weeks, and
      this was conformed by MALD-TOF-MS identification. (2) In addition, 18 proteins
      were present at all time points and another 19 proteins were absent in the model
      group among those identified by MALD-TOF-MS. (3) Fuzheng Huayu Decoction down
      regulated proteins and their expressions increased at 4 and 8 weeks, whereas it
      up-regulated those which decreased at 8, 12 and 16 weeks. CONCLUSIONS: (1) The
      changes in protein expressions, which effect metabolism, neuroendocrine function
      and cell proliferation, are the basis of liver fibrosis. (2) The anti-fibrotic
      effect of Fuzheng Huayu Decoction is holistic, specifically because it can
      decrease the abnormal cell proliferation and can increase the synthesis of normal
      proteins.

PMID- 16792866
TI  - [Effect of magnesium isoglycyrrhizinate on the proliferation and oxidative stress
      of rat hepatic stellate cells in vitro].
AB  - OBJECTIVES: To investigate the effect of magnesium isoglycyrrhizinate on the
      proliferation and oxidative stress of rat hepatic stellate cells (HSCs). METHODS:
      The effect of various concentrations of maganesium isoglycyrrhizinate on the
      proliferation of primary rat HSCs and HSCs strains were measured by making cell
      growth curves and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphennylterazolium bromide
      (MTT) colorimetric assay. Morphological changes of the rat HSCs were also
      studied. After rat HSCs were incubated with various concentrations of maganesium
      isoglycyrrhizinate and ferric nitrilotriacetate (Fe-NTA) for 24 hours, the
      activity of superoxide dismutase (SOD) and contents of malondialdehyde (MDA) in
      supernates were measured to observe the effect of magnesium isoglycyrrhizinate on
      the oxidative stress of rat HSCs. RESULTS: Compared with the control group, the
      proliferation of rat HSCs was significantly inhibited when the concentration of
      magnesium isoglycyrrhizinate in the medium reached a certain level range. In the
      oxidative stress induced by Fe-NTA, magnesium isoglycyrrhizinate, within a
      certain strength range, obviously enhanced the activity of SOD and decreased the
      contents of MDA in supernates of rat HSCs culture media. CONCLUSIONS: Magnesium
      isoglycyrrhizinate could significantly inhibit the proliferation of rat HSCs and
      it, within a certain strength range, exert protective effects in the oxidative
      stress induced by Fe-NTA.

PMID- 16792867
TI  - [Effect of tumor antigen specific CTL induced by dendritic cells on a model of
      human hepatocellular carcinoma in nude mice (LCI-D20)].
AB  - OBJECTIVES: To investigate the cure effect of tumor antigen specific CTL on a
      model of human hepatocellular carcinoma in nude mice LCI-D20. METHODS: Dendritic
      cells (DCs) were induced from peripheral blood mononuclear cells of healthy
      people in vitro by using recombinant human granulocyte-macrophage colony
      stimulating factor (rhGM-CSF) and interleukin-4 (rhIL-4) and were pulsed with
      tumor antigen from hepatocellular carcinoma cell line MHCC97H. Then tumor antigen
      specific cytotoxic T lymphocytes (CTLs) were induced. By intraperitoneal
      injection of tumour antigen specific CTLs into the LCI-D20, the preventive and
      therapeutic effects of these CTLs to HCC in the LCI-D20 model were assessed.
      Cytokine-induced killer (CIK) cells and phosphate buffer solution were used as
      controls at the same time. RESULTS: The weights of tumors in the tumor antigen
      specific CTL group, in the CIK cell group and in the blank group were (1.11+/
      0.63), (1.12+/-0.36) and (2.68+/-0.53) grams respectively (t = 5.18, t = 6.06, P
      < 0.01). The amount of blood alpha fetal protein in the tumor antigen specific
      CTL and CIK groups were (52.1+/-9.7) microg/L and (48.6+/-5.2) microg/L, and was
      (82.2+/-7.2) microg/L in the blank group (t = 17.26, t = 22.07, P < 0.01
      respectively). The metastasis rates in livers were 16.7%, 16.7% and 58.3% in the
      tumor antigen specific CTL, CIK cell and blank control groups respectively (chi2=
      4.44, P < 0.01). The survival time of the mice in the tumor antigen specific CTL
      group was (79.0+/-5.02) days, (73.3+/-7.0) days in the CIK group, and (52.3+/
      5.2) days in the blank group (t = 14.56, t = 17.54, P < 0.01). CONCLUSION: Tumor
      antigen specific CTLs may prevent metastasis in the LCI-D20 model and prolong the
      survival time.

PMID- 16792868
TI  - [Effects of hTERT RNAi on apoptosis of hepatocellular carcinoma cells induced by
      TRAIL].
AB  - OBJECTIVE: To study the effects of human telomerase reverse transcriptase (hTERT)
      RNA interference (RNAi) on biological characteristics of hepatocellular carcinoma
      cell lines HepG2 and SMMC-7721 and on apoptosis induced by tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL). METHODS: Small hairpin hTERT (shTERT)
      sequence was identified by PCR method; hTERT expressions, morphological features,
      cell proliferation and replicative senescence were respectively determined using
      RT-PCR, hematoxylin-eosin (HE) staining, growth curve and beta-galactosidase (b
      Gal) staining; cell cycle and apoptosis were identified using flow cytometry
      after propidium iodide (PI) staining and annexin V/PI double staining. RESULTS:
      shRNA were found in 6/8 HepG2 and 6/6 SMMC-7721 cell clones transformed by the
      recombined plasmid pSilencer 3.1-H1 neo-shTERT. The interference rates of hTERT
      on HepG2 and SMMC-7721 were 100% and 43.3% respectively. Cells in G2-M phases
      increased from 7.1% to 10.6% and from 6.9% to 7.9% respectively; and the
      percentage of replicative senenscence cells increased from 0 to 20.4% and from
      3.6% to 10.0% respectively. The nucleus/cytoplasm ratios of the cells were
      obviously decreased after hTERT RNAi treatment. Moreover, apoptosis of
      hepatocellular carcinoma cells and apoptosis induced by TRAIL were strikingly
      increased by hTERT RNAi (P < 0.05). For example, apoptosis rates were increased
      from 3.5% to 5.2% in HepG2 cells and from 4.8% to 7.9% in SMMC-7721 cells after
      hTERT RNAi treatment. Apoptosis rates were increased from 5.3% to 10.4% in HepG 2
      cells and from 13.9% to 77.2% in SMMC-7721 cells after being treated by 100 ng/ml
      TRAIL for 24 h. However, there were no remarkable changes between control cells
      and untransformed cells. CONCLUSION: hTERT RNAi not only has a significant effect
      on biological characteristics of hepatocellular carcinoma cells, but also
      obviously can increase cell apoptosis induced by TRAIL.

PMID- 16792870
TI  - [Evaluation of the liver reserve using lidocaine test on experimental liver
      injuries in rats].
AB  - OBJECTIVES: To study the effectiveness of the lidocaine test in evaluating the
      liver reserve of rats with experimental liver injury in different phases.
      METHODS: 40 healthy male Wistar rats were divided randomly into experimental and
      control groups. Rats of the experimental group received subcutaneous CCl4 in oil
      injection, and rats of the control group received saline injections.
      Monoethylglycinexylidide (MEGX) test, common hepatic function tests and
      histological examination of the livers were performed on all the rats. RESULTS:
      With the development of the severity in liver injury, the concentrations of the
      serum MEGX in lidocaine test decreased gradually, which were consistent with
      liver histological changes. However, the results from the common liver function
      tests were all abnormal in the experimental group and were not consistent with
      the liver histological changes. CONCLUSION: The results obtained from the MEGX
      test are more agreeable to liver histological changes than those from common
      liver function tests. The results from the MEGX test can represent liver
      histological changes concisely.

PMID- 16792869
TI  - [An analysis of the features of HBx protein distributed in liver cells and its
      expression in E. coli].
AB  - OBJECTIVE: To investigate the features of HBx protein distributed in liver cells
      and its expression in E. coli. METHODS: The expression vectors encoding the full
      length HBx and its mutants were constructed by the routine molecular cloning
      method. HBx protein expression was detected using Western blotting. The
      distribution feature of HBx protein in liver cells was examined using the
      fluorescence confocal microscopy. A series of purified HBx fusion proteins were
      obtained by glutathione-sepharose 4B affinity chromatography. RESULTS: The
      expression vectors were successfully constructed for the full length HBx and its
      mutants. HBx was found distributed uniformly in the nuclei but granularly in the
      cytoplasm of the liver cells. Under optimal conditions, the mutant GST-HBx (72
      120aa) was easily degraded. CONCLUSION: This study may provide a basis for
      further study on the biological function of HBx at the protein level.

PMID- 16792871
TI  - [A clinical and pathological study of nonalcoholic fatty liver disease].
AB  - OBJECTIVE: To study the pathological and clinical features of nonalcoholic fatty
      liver disease (NAFLD). METHODS: Grades and stages of liver lesions in 41 patients
      with NAFLD were analyzed. The relationships between pathohistological features of
      the livers, serum biochemical parameters, ultrasound examination and other
      clinical data of the patients were studied. RESULTS: Among the 41 patients with
      NAFLD (there were 21 with their liver fatty degeneration in grade 1, 15 in grade
      2, and 5 in grade 3). There were 2 of grade 0, grade 1 had 25, grade 2 had 10,
      grade 3 had 3, and grade 4 had 1. Stage 0 of fibrosis was 20, stage 1 was 14,
      stage 2 was 4, stage 3 was 2, and stage 4 was 1. Degree of fatty degeneration was
      not positively associated with the body mass index (BMI) of the patients and the
      ultrasound findings in their livers. Grading of the inflammation was positively
      related to the alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) levels in the blood and ultrasound findings in their livers, but negatively
      to the platelet counts. Staging of fibrosis of the livers was positively related
      to the blood ALT, AST, GGT, and ALP, and negatively to triglyceride levels and
      platelet counts. CONCLUSIONS: Degree of liver fatty degeneration was not
      associated with grades of inflammation and staging of fibrosis of the liver. BMI,
      ALT and AST level, platelet counts, and ultrasound grades of fatty liver were
      associated with the liver histopathological changes of NAFLD patients. Liver
      biopsy is the essential way to make a diagnosis of NAFLD.

PMID- 16792872
TI  - [Evaluation of leptin receptor Lys109Arg polymorphism in patients with non
      alcoholic fatty liver disease].
AB  - OBJECTIVE: To investigate whether leptin receptor Lys109Arg polymorphism
      influences non-alcoholic fatty liver disease. METHODS: Genomic DNA samples were
      extracted from blood of subjects who had received a physical examination.
      Genotyping was performed using oligonucleotide microarray and these fluorescence
      labeled PCR-amplified fragments were hybridized to allele-specific
      oligonucleotide probes. The relevant mutation was confirmed by sequencing
      analysis. RESULTS: A total of 180 subjects (109 males and 71 females) were
      included in the study, 117 of them had fatty liver disease and the other 63 had
      no liver problems and served as healthy controls. There were 144 (80%) subjects
      with GG genotype (Arg109Arg), 33 (18.3%) with GA genotype (Lys109Arg) and 3
      (1.7%) with AA genotype (Lys109Lys). The distribution of leptin receptor
      Lys109Arg polymorphism had no significant difference (P > 0.05) between the fatty
      liver disease patients (95GG, 21GA and 1AA) and the healthy control subjects
      (49GG, 12GA and 2AA). The abdominal wall fat was significantly thicker in AA
      genotype subjects (4.1+/-0.4) cm than that in GA (2.8+/-0.6) cm and GG genotype
      subjects (2.7+/-0.7) cm (F = 5.197, P = 0.006). The serum cholesterol levels in
      AA genotype subjects (5.1+/-0.4) mmol/L was significantly lower than that in AG
      (25.5+/-6.9) mmol/L and GG genotype (27.2+/-8.4) mmol/L subjects (F = 8.164, P =
      0.005). There were no significant differences in age, body mass index, hip
      circumference, waist circumference, blood pressure (BP), percentage of body fat,
      blood protein, triglyceride, HDL and fasting blood glucose between AA, GG and GA
      genotype subjects. CONCLUSION: Leptin receptor Lys109Arg polymorphism may be
      involved in the regulation of distribution of abdominal wall fat thickness and
      cholesterol metabolism. Whether leptin receptor Lys109Arg polymorphism is in any
      way related to fatty liver disease is still not known.

PMID- 16792873
TI  - [The significance and promoter expression of insulin-like growth factor-II gene
      in human hepatocellular carcinoma].

PMID- 16792874
TI  - [The plasma levels of urokinase plasminogen activator and plasminogen activator
      inhibitor-1 and the protein expressions of alpha-SMA and MMP-1 and TIMP-1 in
      patients with different grades of liver fibrosis].

PMID- 16792875
TI  - [The construction of a human serum albumin small gene].

PMID- 16792876
TI  - [Detection of auto-antibodies for diagnosing auto-immunous hepatitis].

PMID- 16792877
TI  - [Study on the epidemiology and HCV genotype distribution of HIV/HCV co-infection
      among HIV infected blood donors in China].

PMID- 16792879
TI  - [A report from the fifth national meeting of liver diseases and the tenth
      anniversary celebration of the Chinese Journal of Hepatology (Zhonghua
      Ganzangbing Zazhi)].

PMID- 16792878
TI  - [Distribution of hepatitis B virus genotypes in Ningxia Hui nationality and its
      clinical significance].

PMID- 16792880
TI  - [An outbreak of human Streptococcus suis serotype 2 infections presenting with
      toxic shock syndrome in Sichuan, China].
AB  - OBJECTIVE: In mid-July 2005, five patients presented with septic shock to a
      hospital in Ziyang city in Sichuan, China, to identify the etiology of the
      unknown reason disease, an epidemiological, clinical, and laboratory study were
      conducted. METHODS: An enhanced surveillance program were established in Sichuan,
      the following activities were introduced: active case finding in Sichuan of (a)
      laboratory diagnosed Streptococcus suis infection and (b) clinically diagnosed
      probable cases with exposure history; supplemented by (c) monitoring reports on
      meningococcal meningitis. Streptococcus suis serotype 2 infection was confirmed
      by culture and biochemical reactions, followed by sequencing for specific genes
      for serotype and virulence factors. RESULTS: From June 10 to August 21, 2005, 68
      laboratory confirmed cases of human Streptococcus suis infections were reported.
      All were villagers who gave a history of direct exposure to deceased or sick pigs
      in their backyards where slaughtering was performed. Twenty six (38%) presented
      with toxic shock syndrome of which 15 (58%) died. Other presentations were
      septicaemia or meningitis. All isolates were tested positive for genes for tuf,
      species-specific 16S rRNA, cps2J, mrp, ef and sly. There were 136 clinically
      diagnosed probable cases with similar exposure history but incomplete laboratory
      investigations. CONCLUSION: An outbreak of human Streptococcus suis serotype 2
      infections occurred in villagers after direct exposure to deceased or sick pigs
      in Sichuan. Prohibition of slaughtering in backyards brought the outbreak to a
      halt. A virulent strain of the bacteria is speculated to be in circulation, and
      is responsible for the unusual presentation of toxic shock syndrome with high
      case fatality.

PMID- 16792881
TI  - [Cohort study on human immunodeficiency virus discordant couples in the
      countryside of central China].
AB  - OBJECTIVE: To establish a cohort of human immunodeficiency virus (HIV) discordant
      couples for follow-up studies and to collect data on frequency of HIV
      heterosexual transmission and related factors. METHODS: A total of 52 HIV
      discordant couples were identified by face to face interview and serological
      testing, in which the HIV negative individuals had no HIV infection behaviors
      including injecting drug use, blood transfusion or having sexual partners other
      than his/her own wife/husband. Three times of follows-up studies were carried out
      in 0.5 year, 1 year and 2.5 years to collect information on their sexual
      practices and condom use through face to face interview together with 20 ml whole
      blood collected to test HIV antibody, CD4+ T cell count and viral load. RESULTS:
      (1) In the period of 2.5 years follow-up, no HIV seroconversion and HIV
      transmission was found. (2) The frequencies of sexual intercourse between once
      per month to once per week were 65.4%, 72.9%, 71.7% and 80.0% at the time of
      cohort setup: 0.5 year, 1 year and 2.5 years of follow-up respectively. The rates
      of "occasional use" to "never use" condoms were 76.9%, 66.6%, 69.1% and 60.0% at
      the time of cohort setup as: 0.5 year, 1 year and 2.5 years of follow-up,
      respectively. No significant difference between different times of follow-up for
      sexual intercourse or condom use. (3) 85.4%, 66.6% and 60.0% of the HIV positive
      individuals kept their CD4+ T cell count stabilized or raised during the 0.5
      year, 1 year and 2.5 years follow-up period, respectively. However, 66.7% of them
      showed stable or declined viral load in the period of 2.5 years follow-up. It
      appeared that stable or raised CD4+ T cell and the stable/declined viral load
      happened simultaneously. CONCLUSION: No transmission was identified in this
      study. The stabilized CD4+ T cell count and viral load might be account for the
      reason of no transmission while the biological factors from host and virus
      related with transmission need to be further studied.

PMID- 16792882
TI  - [Study on the association between hantavirus infection and Rattus norvegicus].
AB  - OBJECTIVE: To further understand the association of hantavirus (HV) harbored and
      transmitted in wild brown rats. METHODS: Rattus norvegicus (n = 570) were trapped
      in 10 sites in Beijing. RT-PCR was used to test rodent lung samples for
      hantavirus infection. Unconditional multivariate logistic regression analysis was
      performed, with PCR positive as the dependent variable and the characteristics of
      Rattus norvegicus population as independent variables. RESULTS: The overall HV
      prevalence in Rattus norvegicus was 9.1% (52/570). Significant association
      between HV infection in Rattus norvegicus and some biological characteristics of
      host population was observed. Adult Rattus norvegicus had a higher HV prevalence
      than juveniles. Males in the reproduction periods and rats with wounds were more
      likely to be infected with HV than others. CONCLUSION: It was further confirmed
      that there existed parallel transmission of HV in Rattus norvegicus hosts.
      Aggression might be the primary mode of HV transmission among male Rattus
      norvegicus.

PMID- 16792883
TI  - [An epidemiological study on domestic violence in Hunan, China].
AB  - OBJECTIVE: To investigate the prevalence of domestic violence (DV) in Hunan.
      METHODS: Using a multi-stage sampling strategy, 9451 households involving 32 720
      persons in urban, rural and industrial areas in Hunan, China were studied.
      Multiform clue investigation and face-to-face interviews were combined to
      investigate the prevalence of DV. RESULTS: A lifetime prevalence of DV was
      reported by 1533 households (16.2%). A total of 1098 households (11.6%) reported
      at least one incident of DV in the previous year. Both lifetime and 12-month
      prevalence of DV varied significantly by geographic setting (P < 0.01). The
      lifetime prevalence abuse rates were: spousal 10.2%, child abuse 7.8%, and elder
      1.5%. With regard to household structure, the lifetime prevalence of DV was
      highest among those remarried families (21.0%), followed by married couples with
      one child and extended families with several generations living together (20.1%
      and 20.0%, respectively). The highest rate of spousal abuse was found among
      remarried families (14.7%), while child and elder abuse was most prevalent among
      extended families (12.4% and 4.1%, respectively). CONCLUSIONS: The findings
      suggested that although the prevalence of DV in Hunan was modest compared to
      Western countries, it remained a serious public health problem affecting over 1
      in 10 households. Furthermore, the prevalence of various types of DV varied by
      geographic setting and family structure, suggesting that diverse geographic
      setting and family constellations carried different risk and protective features.

PMID- 16792884
TI  - [Study on the correlation between adolescents' emotional and behavioral problems
      and life events].
AB  - OBJECTIVE: To study the life events which are correlated with adolescent's
      emotion and behavior problems, and to provide evidence for clinicians and school
      staff to develop intervention for those problems. METHODS: Youth's Self Report
      (YSR) and Adolescent Self-Rating Life Events Check List (ASLEC) were used to
      assess adolescent's emotional and behavioral problems and life events by 'spot'
      study. The referred group consisted of 585 patients from 11 to 18 years old in a
      Mental Health Centre of West China Hospital of Sichuan University from July in
      2002 to March in 2004. Level of IQ was above 5th grade of primary school among
      the study subjects who were willing to fill in the YSR and ASLEC. The non
      referred group was selected in a 1280 students cluster-sample from the schools of
      Chengdu city, whose sex, age and father's career were matched with the referred
      group. Variance inflation factor (VIF) was used to verify that there was no
      collinearity to each other in the 6 factors of ASLEC: interpersonal relationship,
      learning pressure, being punished, losing good adaptation and other. Linear
      stepwise regression was adopted. RESULTS: The YSR scores in referred group were
      higher than those in non-referred group, and the referred group had more
      emotional and behavioral problems than the non-referred one. Partial correlations
      ranged from 0.124 to 0.418 in referred group, and from 0.104 to 0.388 in non
      referred group. Unsatisfied interpersonal relationship, heavy learning pressure,
      having been punished and poor adaptation were likely to increase the risk of
      youth's emotional and behavioral problems. CONCLUSION: More attention should be
      paid to help adolescents in the following areas: solving intrapersonal affairs,
      relieving pressure from learning, avoiding punishment, and improving ability to
      fit themselves to their surroundings.

PMID- 16792885
TI  - [Evaluation on birth defects surveillance system in four counties of Shanxi
      province, China].
AB  - OBJECTIVE: To evaluate the reliability of the birth defects surveillance system
      in four counties with high prevalence of birth defects (Pingding, Xiyang, Taigu
      and Zezhou counties) in Shanxi province, China. METHODS: One township was
      selected from each county as study site. The health workers chosen from township
      or village level were trained to visit families on the outcomes of each pregnancy
      who gave birth during year 2003 in the study site. The number of births and cases
      collected in the study were compared with that from the surveillance system. The
      number of births reported by surveillance system in four counties was also
      compared with the data from the local government. The criteria of evaluation
      were: 1) number of the missing report of births should < or = 5%, 2) the number
      of missing report on major external birth defects cases should < or = 10%.
      Researchers from the Peking University were responsible for examining the quality
      of surveillance in some terminal units of surveillance system. RESULTS: The
      numbers of births reported in the study and from the surveillance system for four
      township were 1043 and 997, respectively. 46 births were missing and the rate of
      misreporting for births was 4.4%. The numbers of birth defects cases reported in
      the study and from the surveillance system were 30 and 29, respectively. 1 case
      of birth defect as missed, and rate of misreporting for birth defects cases was
      3.3%. The total number of births reported from surveillance was similar to that
      in the study in four counties, with a difference of 1.2%. Birth registry data was
      rather readable and special health workers responsible for surveillance work were
      present in all the terminal units of the surveillance system. CONCLUSION: The
      misreporting of births and cases existed in the birth defects surveillance system
      of the four counties in Shanxi province, but were lower than the allowable
      criteria. The surveillance units had better registration, reporting and
      administration of births and birth defect cases. Hence, the quality of the data
      from the surveillance system in these four counties was reliable.

PMID- 16792886
TI  - [Epidemiological features of spontaneous abortion among reproductive Tibetan
      women living at high altitudes areas].
AB  - OBJECTIVE: To study the status of spontaneous abortion among reproductive Tibetan
      women aged 15 - 49 years. METHODS: A cross-sectional survey was conducted on
      reproductive history of Tibetan women and the sample was chosen under the
      stratified multistage cluster random sampling technique. RESULTS: A total number
      of 3741 women were studied with a total number of 10,245 pregnancies. There were
      386 spontaneous abortions reported with an incidence rate of 3.9%. Women living
      in the urban area had a higher rate than living in the rural areas. Women living
      in area where altitudes were above 4500 m, had a 2-time risk of having
      spontaneous abortion than those living in areas below 3500 m. The risk of having
      spontaneous abortion increased among women aged > or = 35 and those with more
      than 3 pregnancies. CONCLUSIONS: High altitude could contribute to the increase
      of spontaneous abortions incidence, suggesting that improvement of maternal care
      and nutrition and reduction of the frequency of pregnancy had important roles to
      play in reducing the incidence of spontaneous abortion among Tibetan women.
      Despite the fact that retrospective study on reproductive history could
      underestimate the incidence of spontaneous abortion, the incidence rate among
      Tibetan women might not be much higher than women living in the lowland areas.

PMID- 16792888
TI  - [Study on serum organochlorines pesticides (DDTs) level, CYP1A1 genetic
      polymorphism and risk of breast cancer: a case control study].
AB  - OBJECTIVE: To study the potential effect of gene-environment interaction between
      CYP1A1 and serum dichlorodiphenyldichloroethane (DDT) levels on the risk of
      breast cancer in women, in China. METHODS: A case-control study was conducted.
      From Dec. 2003 to Sep. 2004, 104 women with histologically confirmed breast
      cancers and 154 noncancerous controls from a community were enrolled in this
      study. Risk factors information of breast cancer was investigated by a
      questionnaire. Serum p, p'-dichlorodiphenyldichloroethane (p, p'-DDT) and 1, 1
      dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels were tested by GC
      ECD. CYP1A1 m2 gene type was tested by allele special-PCR method. RESULTS: Serum
      DDT levels of case and control were (36.90 +/- 79.41) ng/ml and (50.60 +/-
      150.70) ng/ml respectively. Serum 1, 1-dichloro-2, 2-bis (p-chlorophenyl)
      ethylene (p, p'-DDE) levels of case and control were (7.43 +/- 11.10) ng/ml and
      (8.96 +/- 11.30) ng/ml respectively. No statistically significant differences
      were found between the two groups with geometric mean t-test (P > 0.05). Compared
      with women who had homozygous wild-type CYP1A1 m2 genotype, significantly
      increased risks of breast cancer were found for women with the CYP1A1 m2
      homozygous variant genotype [odds ratio (OR) = 2.61, 95% confidence interval
      (CI): 1.00 - 6.80]. Among premenopausal women, compared with women with
      homozygous wild-type of CYP1A1 genotype (Ile/Ile) and low serum DDT level (DDT
      serum level < or = 42.93 ng/ml), women with at least one variant allele of CYP1A1
      m2 genotype and high serum DDT level (DDT serum level > or = 42.93 ng/ml) had
      higher risk of breast cancer (OR = 4.35, 95% CI: 1.140 - 16.950). CONCLUSIONS:
      CYP1A1 m2 genetic polymorphism was associated with increased risk of female
      breast cancer while DDT exposure might have increased the risk of breast cancer
      among premenopausal women with CYP1A1 m2 variant genotype.

PMID- 16792889
TI  - [Study on the maternal mortality ratio from 1995 to 2004 among residential and
      migrant women in Beijing].
AB  - OBJECTIVE: To analyze the maternal mortality ratio (MMR) of residential and
      migrant women in Beijing. METHODS: A retrospective study from 1995 to 2004 was
      performed to analyze data from the maternal death cases. RESULTS: The MMR of
      resident and migrant of Beijing from 1995 to 2004 were 17.9 and 51.3 per ten
      thousand respectively. The main reasons of maternal deaths among residents were
      embolism (21.2%), hypertensive disorder complicating pregnancy (18.3%),
      postpartum hemorrhage (14.4%) and ectopic pregnancy/heart disease (9.6%). The
      main reasons of migrant maternal deaths were postpartum hemorrhage (25.2%),
      embolism (19.7%), hypertensive disorder complicating pregnancy (17.3%) and liver
      disease (9.5%). The avoidable deaths were accounted for 18.9%. CONCLUSION: The
      MMR in Beijing local residents was close to that in developed countries. To
      further reduce MMR in Beijing would depend on the better administration of
      related issues among floating population. Poor quatily delivery must be banned
      together with strengthening the training programs on health workers. It is also
      important to improve the knowledge and skills of medical staff for rescuing the
      complications of pregnancy and ectopic pregnancy.

PMID- 16792890
TI  - [Study on the relative risk factors of adult measles in a case-control study in
      Qingdao city].
AB  - OBJECTIVE: To explore the relative risk factors of adult measles in Qingdao city.
      METHODS: Case-control study was used to collect the information from 70 adult
      measles cases and 140 controls. Information would include general social and
      demographic characteristics, history and times regarding measles vaccination,
      demography of the study of population etc. RESULTS: The case group had lower
      proportion of measles vaccination (chi2 = 26.88, P < 0.05, OR = 5.12, 95% CI:
      2.69 - 9.73) than the control group with statistical significance. The
      vaccination frequencies were stratified as three ranks: 0, 1, > or = 2 times for
      analysis. When having 0 and 1 time measles vaccination, no statistical
      significance was found in these two groups (chi2 = 1.86, P = 0.173), but there
      were statistical significance between 0 and > or = 2 times (chi2 = 45.24, P =
      0.000, OR = 13.35, 95% CI: 5.80 - 30.71), 1 and > or = 2 times (chi2 = 26.23, P =
      0.000, OR = 7.91, 95% CI: 3.37 - 18.59) in the two groups. It was also found that
      the proportion of floating population was higher in case group than that of the
      control group (chi2 = 21.60, P < 0.01, OR = 4.06, 95% CI: 2.21 - 7.45). At the
      same time, statistically significant correlation was found between adult measles
      and average family incomes (chi2 = 2.23, P < 0.05, OR = 2.08, 95% CI: 1.15 -
      3.76) by single-factor statistical analysis. CONCLUSION: Results showed that
      'without history of measles vaccination' was key relative risk factor for the
      adult measles while being a part of 'floating population' and those having lower
      incomes were among vulnerable groups.

PMID- 16792892
TI  - [Study on the development of a choropleth atlas on cancer mortality using the
      inverse distance weight interpolation in the 1990's].
AB  - OBJECTIVE: To draw a chorochromatic atlas of mortality on China Cancer Database
      in order to display the geographical distribution of selected diseases in China
      and to identify its demographic and disease-specific patterns in the 1990's.
      METHODS: The source of data was from nationwide cause-of-death surveys conducted
      in the 1990's. Standardized rates were computed by direct method using the
      population age distribution in 1964 as the standard of weights. Inverse distance
      weight (IDW) was applied as the method of interpolation with the help of Arcview
      system to draw a choropleth map of cancer mortality. RESULTS: The IDW maps of
      cancer mortality shows a continuous and smooth variation, especially compared
      with maps drawn by filling method. CONCLUSION: With the application of inverse
      distance weight interpolation, it seemed feasible to draw continuous map of
      cancer on sampling data.

PMID- 16792893
TI  - [Analysis on factors influencing the smoking behaviors among male secondary
      school students under the structural equation model].
AB  - OBJECTIVE: To analyze the direct and indirect outcomes of influencing factors on
      smoking behaviors among adolescents. METHODS: Self-administered questionnaires
      were used to collect smoking-related information from 2021 respondents.
      Measurement models were built by confirmatory factor analysis and parameters were
      estimated by ERLS method. The final structural equation model was determined by
      comprehensive evaluation and necessary modification. RESULTS: Three latent
      variables were extracted from 10 manifest variables of environment, while only
      one latent variable was identified from 9 manifest variables of attitudes. The
      goodness of fit for the structural equation model was satisfactory that all
      indices had met corresponding requirements. The final model could explain 38.8%
      of the variance of smoking behaviors. Four factors (smoking environment, smoking
      restriction from parents and teachers, determination of cigarette refusal and
      attitudes toward smoking) were directly affecting the smoking behaviors, while
      another three factors (grade, health knowledge and school environment) had
      indirect impacts. According to the percentages of their contribution, the risk
      factors were ranked as follows: smoking environment (45.76%), attitudes toward
      smoking (19.88%) and grade at school (0.44%). Similarly, the top protective
      factor were: determination of cigarette refusal (16.61%), followed by smoking
      restriction from parents and teachers (10.51%), health knowledge (3.89%) and
      school environment (2.92%). CONCLUSIONS: Heath knowledge had minor effect on
      smoking in adolescents but could indirectly affect their smoking behaviors
      through changing their belief. Grade at school had a doubled influence on
      smoking, but mainly served as a risk factor. Tobacco control measures for
      adolescents should not only be limited to health education but environment
      factors as well.

PMID- 16792894
TI  - [Influenza surveillance from 1999 to 2005 in Liaoning regions].
AB  - OBJECTIVE: To investigate the prevalence and subtypes of influenza viruses in
      Liaoning regions from November 1999 to March 2005. METHODS: Influenza virus was
      isolated by embryonated eggs together with cell culture and subtypes, identified
      by HI test. RESULTS: During the study in 1999 - 2005, a total number of 2713 swab
      specimens were collected in different cities in Liaoning regions in which 188
      strains were identified for influenza viruses with an average rate as 7.0%. A
      total number of 1466 swab specimens were collected by both Centers for Disease
      Control and Prevention in Dalian city and Liaoning province, and 167 strains were
      identified positive with an average rate of 11.4%. Influenza A3, A1 and
      B/Yamagata all appeared before March 2002 which were predominant strains.
      However, since then Influenza A1 has never appeared again in Liaoning regions and
      B showed some changes, from Yamagata to Victoria, the characteristics on the
      prevalence of influenza appeared only in the period of November to February.
      CONCLUSION: It was meaningful to analyze the surveillance data of influenza in
      different years in Liaoning regions in order to better understand the
      characteristics of influenza and the shifting of subtype.

PMID- 16792896
TI  - [Sequence analysis of the HA1 regions of hemagglutinin genes of influenza viruses
      (H3N2) isolated from children in Beijing from 1998 - 2004].
AB  - OBJECTIVE: To characterize the HA1 regions of hemagglutinin gene of influenza
      viruses (H3N2) isolated from children in Beijing from 1998 - 2004. METHODS: The
      HA1 regions of hemagglutinin gene were amplified by RT-PCR from the viruses
      isolated and identified as A3 (H3N2) from clinical samples collected from infants
      and children during the peak seasons of influenza between 1998 and 2004. PCR
      products were sequenced or cloned into T-A vector and were analyzed after being
      sequenced. RESULTS: The HA1 regions of hemagglutinin genes amplified from those
      isolates were 987 bp in length, encoding a protein of 329 amino acids in length.
      The identities of nucleotides and amino acids among these H3N2 isolates in
      Beijing and vaccines strains from 1998 - 2004 were 95.5% - 100.0% and 93.0% -
      100.0%, respectively. The homology of the HA1 regions were related to the date of
      virus isolation, meaning the homology was higher among those strains isolated in
      nearer dates than others. Seven potential N-linked glycosylation sites in the HA1
      regions located at amino acid positions 8, 22, 38, 63, 126, 165 and 285 were
      conserved in all the viruses analyzed. Two sites at 122 and 133 were inserted in
      those virus isolated after 1997, and another site at 144 appeared in those
      isolated after 1999. More amino acid substitutions located in the five putative
      antigenic sites or receptor binding sites were found more in the isolates than
      the isolates from previous year. Phylogenetic analysis showed new branches
      appeared continuously during 1998 - 2004. The strains isolated during winter in
      2004 belonged to different branches, suggesting the appearance of new variants.
      CONCLUSION: Amino acid substitutions continuously occurred in the HA1 regions of
      hemagglutinin genes in influenza virus (H3N2) isolated from children in Beijing
      from 1998 - 2004, which might have resulted in antigenic drift and led to the
      appearance of new variants.

PMID- 16792897
TI  - [Study on the association between transforming growth factor alpha gene TaqI
      variant and cleft lip with or without cleft palate].
AB  - OBJECTIVE: To study the association between transforming growth factor alpha gene
      (TGFalpha) TaqI variant and nonsyndromic cleft lip with or without cleft palate
      (nsCL/P) in Chinese population. METHODS: TGFalpha TaqI variant was detected using
      polymerase chain reaction-restriction fragment length polymorphism for DNA
      samples of the 149 triads with nsCL/P affected child. We performed the
      Transmission/disequilibrium test and the family-based association study (FBAT) to
      identify the associations between this variant and risk of nsCL/P. RESULTS:
      Significant distortion of C2 allele at TGFalpha TaqI locus in nsCL/P groups (P >
      0.05) was not found. In the family-based association test, C2 allele and
      offspring C2C1 genotype was not found to be significantly associated with an
      increase risk of nsCL/P (P > 0.05). CONCLUSION: Our findings did not suggest an
      association between offspring TGFalpha TaqI variant and the increased risk of
      nsCL/P in Chinese population.

PMID- 16792898
TI  - [Construction of recombinant lentivirus vaccine with single round replication].
AB  - OBJECTIVE: To develop a safe and effective lentivirus vaccine model and provide
      insights into the development of other lentivirus vaccines. METHODS: In this
      study, a construct of pGPT was made by deleting env gene in the infectious Equine
      infectious anemia virus (EIAV) molecular clone of WU57. Since the overlaping of
      EIAV Rev gene with env gene, there was no Rev gene in the construct of pGPT. For
      compensation of Rev function, the construct of pGPTC was made by inserting 4
      copies of constitutive RNA transport elements (CTEs) from Mason-Pfizer monkey
      virus into the construct of pGPT. In addition, a construct designated pTEB
      expressing EIAV Env protein was made while env gene-minus viruses were made by co
      transfection of pGPT/pTEB or pGPTC/pTEB into 293 cells. Western blot was used to
      identify the development of recombinant virus particles. Then immunofluorescence
      assay was used to evaluate the infectivity of recombinant virus particles in
      vitro. RESULTS: EIAV proteins expression was detected in the supernatant of
      transfected 293 cells by Western blot within pGPTC/pTEB transfected cells.
      However, no evidence of EIAV proteins expression was observed within pGPT/pTEB
      transfected cells. EIAV proteins expression was detected in the first round but
      not in the second round infected EK cells with EIAV(GPTC) by immunofluorescence
      assay. CONCLUSION: Rev/RRE was necessary for expression of viral structural
      proteins; CTEs from Mason-Pfizer monkey virus was functionally interchangeable
      with EIAV Rev/RRE to help RNAs transportation out of nucleus to express
      structural proteins and EIAV particles were produced in the transfected 293
      cells. A live EIAV recombinant virus with single round infection had been
      developed.

PMID- 16792900
TI  - [Development of an immunochromayography assay method for the detection of
      Yersinia pestis].
AB  - OBJECTIVE: To develop a method of immunochromatography assay (ICA) with
      sensitive, specific, rapid, simple and suitable for the detection of Yersinia
      pestis antigen at the local laboratories. METHODS: Colloidal gold labeled with
      the anti-F1 antibody of Yersinia pestis, was connnected with the anti-F1 antibody
      of Yersinia pestis to pyroxylin membrane and assembled them to the dipstick of
      ICA. RESULTS: Results showed that the rates of sensitivity for F1 antigen and
      Yersinia pestis were 1 ng/ml and 1.56 x 10(5) CFU/ml respectively. However,
      Yersinia pseudotuberculosis et al could not be detected by dipstick of ICA.
      CONCLUSION: The method of ICA appeared to be consistent to those of r-IHA with
      better specificity and sensitivity but was simple and rapid for the detection of
      Yersinia pestis and F1 antigen.

PMID- 16792902
TI  - [Study on the correlation between coronary heart disease and chronic
      periodontitis].
AB  - OBJECTIVE: To explore the correlation between angiographically-defined coronary
      heart disease (CHD) and chronic periodontitis (CP). METHODS: 277 cases with CHD
      (case group) and another 238 with no agiographic evidence of CHD (control group)
      were compared on their traditional cardiovascular risk factors, as: oral health
      status and probing depth, clinical attachment level, gingival recession, as well
      as number of missing teeth. Other related risk factors of CHD were included in a
      stepwise logistic regression analysis. RESULTS: Data from univariate analysis
      showed that there was significant difference in CP, plasma triglyceride, high
      density lipoprotein cholesterol (HDL-C), fast glucose, white blood count,
      hypertension and smoking between patients with CHD and those with out CHD (P <
      0.01 - 0.001). Multiple factorial logistic regression analysis showed that CP,
      hypertension, diabetes mellitus, HDL-C were strongly correlated with the
      incidence of CHD. Significant dosage-effective response was also found in the
      relationship between CP and CHD (P < 0.001). Further studies also suggested that
      the severity of CP paralleled the severity of CHD. CONCLUSION: The results
      indicated that CP might serve as an independent risk factor of CHD and
      significantly enhance the risk and severity of CHD. Our study suggested that the
      elimination of probable risk factors in oral cavity was indispensable during the
      process of the prevention of CHD in order to prevent acute coronary events.

PMID- 16792904
TI  - [A case-control study on congenital heart diseases with methylenetetrahydrofolate
      reductase gene, cystathionine beta-synthase gene, and environmental factors].
AB  - OBJECTIVE: To explore congenital heart diseases (CHD) in their offsprings in
      association with parental methylenetetrahydrofolate reductase (MTHFR) gene C677T,
      cystathionine beta-synthase (CBS) gene T833C, and environmental factors. METHODS:
      A 1:1 case-control study was carried out to investigate 115 pairs of case and
      controlled children and their parents, and the parents' MTHFR gene 677 C-->T
      mutation and CBS gene 833 T-->C mutation were also identified. The possible risk
      factors were analysed by simple and multiple factors logistic regression methods.
      RESULTS: Results revealed that 5 factors were related to the occurrence of CHD in
      the offsprings: maternal exposures to pesticides in the early stage of pregnancy
      (OR = 8.62), suffering from diseases during pregnancy (OR = 2.069), catching cold
      in the early stage of pregnancy (OR = 4.125), under depressed or nervous
      condition during pregnancy (OR = 4.653), maternal MTHFR 677TT genotype (OR =
      3.872). CONCLUSION: These results suggested that maternal MTHFR 677TT genotype
      was one of the risks to the occurrence of CHD in offspring but parents' CBS gene
      833 T-->C mutation did not get involved in CHD. In addition, the occurrence of
      CHD was related to maternal exposures to pesticides, catching a cold, suffering
      from diseases, depressed or under nervous condition in the early stage of
      pregnancy or during pregnancy.

PMID- 16792905
TI  - [Study on the dissemination of human immunodeficiency virus risk behaviors in a
      floating workers coming from the countryside in China].
AB  - OBJECTIVE: To explore the pattern of transmission of human immunodeficiency virus
      through risky sexual behaviors (RSB) in floating workers coming from the
      countryside to the cities. METHODS: Data were collected anonymously through a
      structured questionnaire survey in 1595 men from Hangzhou and Guangzhou cities,
      using a multi-stage sampling method. Data from both preliminary analyses and
      multivariate regression analysis would show the cumulative adoption of RSB over
      time and the identification of factors associated with the adoption in this
      population from the two areas. RESULTS: 57.9% - 88.1% of the study samples with
      the pre-stage RSB (receiving shampoo, massage or leisure-seeking activities from
      "sexual workers") and 79.9% of those with commercial RSB were initiated during
      the period when they were working away from their home-towns. The highest
      adoption rate (15.2% - 26.8%) was happened in the third month after moving to the
      urban areas for pre-stage RSB, while the highest rate (14.4%) was noticed in the
      sixth month for the commercial ones. The transition interval between the two
      behaviors was around 3 months. The cumulative rate was peaked from 57.3% to 70.4%
      for pre-stage RSB and 48.9% for commercial RSB. The cumulative adoption curves
      showed that the robust increment was more pronounced in the pre-stage than in the
      commercial RSB. Most of the early adopters were married and holding higher
      hedonistic beliefs for the commercial RSB. Communication of sex information and
      behavioral adoption of RSB was associated with the perceived stress and
      hedonistic beliefs. CONCLUSION: RSB epidemics seemed to be social and group
      phenomena, suggesting that related social strategies should be developed in order
      to control the RSB in this population.

PMID- 16792911
TI  - [A novel genetic defect in a Chinese family with inherited coagulation factor
      XIII deficiency].
AB  - OBJECTIVE: To identify the genetic defect of inherited coagulation factor (F)
      deficiency in a Chinese family and to explore its molecular mechanism. METHODS:
      The activity and antigen of plasma F were measured by photometric test and enzyme
      linked immunosorbent assay, and rocket-electrophoresis, respectively. All the
      exons and exon-intron boundaries of the FA subunit gene were amplified by PCR and
      then DNA sequencing was performed. Restriction endonuclease analysis was used for
      the PCR products of the family members and 80 healthy donors to exclude gene
      polymorphism. RESULTS: Rapid dissolution of the proband's fibrin clot occurred
      within 30 minutes, and antigen of his plasma F was significantly decreased, two
      compound heterozygous missense mutations (a C to T transition at nucleotide
      177,246 which caused Arg703Trp, and a A to G transition at nucleotide 177,286
      which caused His716Arg) in exon 15 of FA subunit gene were found. The possibility
      of gene polymorphism was excluded by restriction endonuclease analysing. Each of
      these two missense mutations was respectively found in his mother and father.
      Molecular modeling based on 3D crystallographic data predicted that the mutant
      protein decreased stability and was likely to be rapidly degraded. CONCLUSIONS:
      The inherited F deficiency in the Chinese family is caused by two compound
      heterozygous missense mutations-Arg703Trp and His716Arg in the FA subunit, which
      to our knowledge, are reported for the first time.

PMID- 16792912
TI  - [Studies on inherited coagulation factor VII deficiency and tissue factor
      abnormality in a pedigree].
AB  - OBJECTIVE: To investigate the mechanism of clinical haemorrhage in an inherited
      coagulation factor VII (FVII) deficiency and tissue factor abnormality pedigree.
      METHODS: All exons, exon-intron boundaries and the 3', 5' untranslated sequences
      of FVII and tissue factor (TF) genes were amplified by PCR and sequenced
      directly. Any mutation identified by direct sequencing was confirmed by reverse
      sequencing. FVII cDNA of the proband was synthesized with random primers and
      amplified by nest PCR. RESULTS: 55C-->T heterozygous mutation located in promoter
      of FVII gene was identified in the proband. The heterozygous mutation was derived
      from his mother. Tracing the other pedigree members found that his sister had the
      same heterozygous mutation and the others had wild-type FVII genes. A 9363 C-->T
      (Arg131Trp) heterozygous polymorphism in TF gene, which was 2.63% frequency of T
      allele polymorphism, was found in all of the pedigree members. CONCLUSION: It was
      the first report that the -55C-->T heterozygous mutation in FVII gene and the
      Arg131Trp heterozygous polymorphism in TF gene explained the clinical symptom of
      the proband.

PMID- 16792913
TI  - [Determination of the ADAMTS13 antigen and its activity in TTP patients and
      carriers].
AB  - OBJECTIVE: To investigate the antigen levels and activity of von Willebrand
      factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura (TTP)
      patients and carriers. METHODS: 28 samples from 13 TTP patients and 10 samples
      from the carriers were examined. The activity of ADAMTS13 was measured by residue
      collagen binding assay, and antigen by a newly developed sandwich ELISA. RESULTS:
      The mean ADAMTS13 level in Chinese normal controls (CN) was (600.93 +/- 145.36)
      mU/ml (n = 26) comparable to the level (1000 mU/ml) in pooled normal Caucasian
      plasma, and the activity was (74.79 +/- 11.81)%. Both the antigen level and
      activity of ADAMTS13 in congenital TTP patients either before plasma exchange
      (pre-PE) or interval relapse were quite lower than those in normal control, but
      were increased after PE (post-PE). The antigen was (331.40 +/- 109.85) mU/ml (P <
      0.01, n = 10), and activity was (66.79 +/- 12.82)% (P > 0.05). The ADAMTS13
      levels pre-PE in idiopathic TTP was (98.7 +/- 82.08) mU/ml (n = 11, P < 0.01),
      and that post-PE was up to (449.4 +/- 232.33) mU/ml (P < 0.01, n = 10). The
      activity of ADAMTS13 in patients pre-PE and post-PE were (22.23 +/- 19.07)% (P <
      0.01) and (60.92 +/- 22.33)% (P > 0.05) respectively. In a secondary TTP patient
      the ADAMTS13 antigen was much higher than that in CN, and the activity was 6.00%.
      CONCLUSION: The antigen and activity of ADAMTS13 in most TTP patients pre-PE are
      deficient, and these two indices in most TTP patients are paralleled. The reason
      for ADAMTS13 deficiency is congenital shortage or clearance by immune system, but
      it is unknown that why in some patients the ADAMTS13 antigen is extremely high
      but its activity is quite low.

PMID- 16792915
TI  - [The immunoreactivity of IgG and its fragments from ITP patients and their
      effects on platelet aggregation function].
AB  - OBJECTIVE: To prepare ITP plasma IgG and its F(ab')2 fragments and investigate
      their immunoreactivity to platelet GPIIb/IIIa and/or GPIb/IX and their effects on
      platelet aggregation function. METHODS: The ITP patients having inhibitory
      autoantibody to the platelet aggregation were selected by modified MAIPA and
      platelet aggregation test with turbidimetry. Plasma IgG and its F(ab')2 fragments
      were prepared by streptococcal protein A affinity column and pepsin digestion.
      The immunoreactivity and the effects on platelet aggregation function of the
      whole antibody and its fragments were detected by modified MAIPA and platelet
      aggregation test, respectively. RESULTS: (1) Anti-platelet GPIIb/IIIa and/or
      GPIb/IX autoantibodies were detected in 34 of 68 (53.6%) ITP patients' plasmas
      and that from 5 patients significantly inhibited the platelet aggregation induced
      by ADP or ristocetin. (2) By using protein A column combined with protease
      digestion, pure IgG and its F(ab')2 fragments were successfully obtained. (3) The
      purified IgG and its F(ab')2 fragments retained the ability to bind to their
      respective glycoproteins and inhibited the platelet aggregation function, whereas
      the IgG depleted plasma lost the ability of binding to the platelet GPs.
      CONCLUSIONS: F(ab')2 fragment of the IgG antibody is a functional fragment, which
      not only has the binding ability to the platelet GPs but also inhibits the
      platelet aggregation function in a dose-dependent manner.

PMID- 16792916
TI  - [Regulation of anticoagulation effect of human umbilical vein endothelial cells
      by thrombomodulin gene transfection].
AB  - OBJECTIVE: To transfect pcDNA3.1/hTM plasmids containing human thrombomodulin
      (hTM) gene into human umbilical vein endothelial cells (HUVECs), and investigate
      the expression of hTM and anticoagulating function of transfected HUVECs.
      METHODS: HUVECs were transfected with pcDNA3.1/hTM by lipofectin. Expression of
      hTM mRNA was determined by semi-quantitative RT-PCR, hTM antigen on HUVECs
      membrane by immunohistochemistry, and activated protein C (PC) in HUVECs by
      chronometry. By using a semiautomatic coagulator, the effect of the reacting
      liquid from transfected HUVECs mixed with PC from normal peripheral blood was
      assayed. RESULTS: About 10% HUVECs were transfected by pcDNA3.1/hTM with high
      level hTM mRNA and protein expression. Activated PC produced by pcDNA3.1/hTM
      group, pcDNA3.1(+)/neo group and untransfected group was (2.80 +/- 0.43)
      microg/ml, (0.75 +/- 0.08) microg/ml and (0.85 +/- 0.11) microg/ml, respectively.
      APTT was (51.68 +/- 2.73) s, (38.38 +/- 2.44) s, (39.65 +/- 2.39) s, (33.93 +/-
      1.73) s and (34.60 +/- 1.86) s and PT was (21.89 +/- 1.66) s, (20.56 +/- 1.74) s,
      (20.42 +/- 2.04) s, (19.57 +/- 1.36) s and (20.16 +/- 1.35) s in pcDNA3.1/hTM
      group, pcDNA3.1(+)/neo group, untransfected group, inactivating PC group and
      control, respectively. CONCLUSIONS: The pcDNA3.1/hTM plasmid could be transfected
      into endothelial cells and expressed biologically functioning hTM protein on
      HUVECs membrane. Activated PC could inhibit intrinsic coagulation pathway
      obviously with slight effect on extrinsic pathway.

PMID- 16792917
TI  - [Effect of anti-Helicobacter pylori ureB monoclonal antibody on platelet
      aggregation and activation, and its mechanism study].
AB  - OBJECTIVES: To study the effect of monoclonal antibody (McAb) against
      helicobacter pylori (Hp) ureB, 1F11 on platelet aggregation and activation, and
      its mechanism. METHODS: The relativity between human platelet glycoproteins (GPs)
      and Hp ureB was identified by Western blot and FCM. Platelet aggregation was
      measured by turbidimetry, and P-selectin and TXB2 assay by ELISA. RESULTS: 1F11
      could bind to platelet GPIIIa, and ADP-induced platelet aggregation was inhibited
      by 1F11 in a dose-dependent manner. However, 1F11 had no effect on plasma P
      selectin and TXB2 induced by ADP. The FCM results show that the positive rates of
      platelet binding to FITC-SZ21 was decreased from 99.5% to 77.4% after addition of
      1F11. CONCLUSION: McAb against Hp ureB 1F11 inhibits platelet aggregation through
      binding to platelet GPIIIa but does not block platelet activation. There might be
      crossed-epitopes on Hp ureB and platelet GPIIIa, and Hp infection might be
      involved in ITP immunopathology.

PMID- 16792918
TI  - [Analysis of X ba I polymorphism of FVIII gene and its application on prenatal
      diagnosis for hemophilia A].
AB  - OBJECTIVE: To establish the linkage methods of X ba I polymorphisms specific for
      FVIII gene intron 22, and to find a rapid and simple system for haemophilia A
      (HA) carrier detection and prenatal diagnosis. METHODS: A long PCR to amplify
      FVIII gene intron 22 followed by X ba I digestion was used to assay the gene rate
      and heterozygosity rate of 206 unrelated people. Detection of intron 22 inversion
      by long distance PCR (LD-PCR) and XbaI, BclI, Hind III, DXS52, STR polymorphism
      within intron 13 and 22 by hereditary linkage analysis were assays in 20 HA
      pedigrees. RESULTS: The gene rate and polymorphism information contents of 206
      people were 0.5475 and 0.4955 respectively, 7 of 20 HA families were diagnosed as
      intron 22 inversion, 6 of 13 non-inversion HA families were diagnosed by X ba I
      linkage analysis, 8 of 13 non-inversion HA families were diagnosed by two or more
      linkage analysis. CONCLUSIONS: The improved X ba I linkage analysis is a specific
      and useful molecular diagnosis marker. LD-PCR and five-linkage analysis can be
      used in prenatal HA gene diagnosis.

PMID- 16792919
TI  - [Alterations in coagulation in patients during transplant conditioning regimen
      before allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate the alterations in coagulation in patients during
      conditioning with modified busulfan plus cyclophosphamide (BU/CY) +/-
      antithymocyte globulin (ATG) regimen before allogeneic hematopoietic stem cell
      transplantation (allo-HSCT), and to assess the effect of ATG on coagulation
      system. METHODS: Thirty-five patients with various hematological malignancies
      undergoing allo-HSCT were assessed. Of them, 19 patients with HLA-matched sibling
      donors (group A) were conditioned with modified BU/CY regimen, 16 with HLA
      mismatched family members or HLA-matched unrelated donors (group B) were
      conditioned with modified BU/CY + ATG regimen. Blood samples were collected
      before the beginning of conditioning till d + 1 after allo-HSCT. The following
      parameters were measured: prothrombin time (PT), activated partial thromboplastin
      time (APTT), fibrinogen (Fg), antithrombin (AT), D-Dimer, fibrin degradation
      product (FDP), platelet (BPC), liver enzymes and bilirubin. FVIII: C, FIX: C,
      FXI: C and FXII: C in prolonged APTT blood samples were also determined. Clinical
      hemorrhagic symptoms were monitored. RESULTS: During conditioning, temporary
      lengthening of APTT, persistent rising in Fg and declining of BPC were observed
      in the two groups. Alterations of Fg and BPC were more significant in group B
      than in group A. Transient D-Dimer increase occurred only in group B on
      administration of ATG. Among intrinsic pathway coagulation factors, FXII: C and
      FXI: C were commonly decreased while APTT prolonged. No difference between the
      two groups was found with regard to PT, FDP, AT and liver parameters which
      remained in normal ranges. Most of patients in the two groups did not have overt
      bleeding manifestations. CONCLUSIONS: Modified BU/CY +/- ATG conditioning regimen
      can induce subclinical alterations in coagulation. The regimen containing ATG has
      more significant effect on coagulation parameters.

PMID- 16792920
TI  - [Study of 161 chronic idiopathic myelofibrosis patients for clinicopathological
      staging].
AB  - OBJECTIVE: To investigate the significance of clinicopathological stage of
      chronic idiopathic myelofibrosis (CIMF) in WHO classification of 2001. METHODS:
      Histopathological analysis of bone marrow biopsy plastic-embedded sections
      stained with H-G-E and Gomori's stains and clinical features of 113 cases
      previously diagnosed as primary myelofibrosis (PMF) and 48 cases MPD-U (total of
      161 cases which including male 79 and female 82) were studied retrospectively.
      RESULTS: There was no significant differences on the clinical features among the
      cellular phase, collagen fiber phase, sclerotic phase and osteomyelosclerosis of
      113 previously diagnosed patients. According to WHO classification 2001 of CIMF,
      previously diagnosis in 48 cases with MPD-U was WHO pre-CIMF, and in 113 cases
      with PMF was WHO CIMF-Fs. There were significant differences between of WHO pre
      CIMF and WHO CIMF-Fs about clinicopathological features except age. The
      percentage of immature granulocytes, normoblasts, lymphocytes in peripheral
      blood, the size of hepatosplenomegaly, and the percent age of tear drop-like red
      blood cells in pre-CIMF were significantly lower than those in CIMF-Fs (P <
      0.05). However, the number of hemoglobin and platelets in patients with pre-CIMF
      were significantly higher than that with CIMF-Fs (P < 0.01). CONCLUSION: pre-CIMF
      and CIMF-Fs in clinical and histopathological features were different development
      stage of CIMF, while osteomyelosclerosis is a variant of CIMF, but not an
      independent disease.

PMID- 16792921
TI  - [Study of deletion of derivative chromosome 9 in patients with Ph+ chronic
      myeloid leukemia].
AB  - OBJECTIVE: To determine the frequency of the derivative 9 [der(9)] deletion among
      chronic myeloid leukemia (CML) patients with classic and variant Ph
      translocations, and assess the correlation between this deletion and clinical
      prognosis. METHODS: Cytogenetic analysis of bone marrow cells was performed by
      direct method and/or 24 h culture method. RHG banding was used for karyotype
      analysis. Dual-color and dual-fusion DNA probe was used to perform FISH for
      investigating the deletion of der(9) in Ph+ CML patients. RESULTS: Cytogenetics
      studies showed typical Ph translocation in 76/105 and variant Ph translocation in
      29/105 cases. Interphase-FISH studies showed deletion of der(9) in 12 (15.8%) of
      76 patients with classic Ph translocation and in 4 (13.7%) of 29 patients with
      variant translocation. The frequency of deletion was similar in classic and
      variant translocations (P > 0.05). When the deletion was seen in the patient, it
      was present in all the Ph+ metaphases and nuclei. In 3 patients there were mixed
      cell populations with either 5'-abl or 3'-bcr deletion and all the 3 patients had
      both 5'-abl and 3'-bcr deletion. The median survival time of patients with
      deletion was significantly shorter than those without deletion (34 months vs 76
      months; P < 0.05). CONCLUSION: Deletion of der(9) is seen in about 1/6 of Ph+ CML
      patients in our study on Chinese CML patients, Ph+ CML patients with the deletion
      have shorter median survival time than those without it, indicating that it is a
      poor prognostic index.

PMID- 16792922
TI  - [Abnormal expression of cCD79a/cCD22 in acute myeloid leukemia with t (8;21)].
AB  - OBJECTIVE: To report abnormal expression of cCD79a/cCD22 in four cases of acute
      myeloid leukemia (AML) with t (8;21). METHODS: The characteristics of morphology,
      immunophenotype, chromosome karyotype (MIC) and clinical manifestations of 4 AML
      patients with t (8;21) expressing cCD79a/cCD22 were analyzed. RESULTS: The
      features of the 4 patients were: (1) no difference in gender; (2) young age; (3)
      exmedullary infiltration may be present; (4) normal number of white blood cells
      in peripheral blood; (5) morphology showed acute myeloid leukemia with high
      percentage of blast cells; (6) B-lymphoid and myeloid immunophenotype, and high
      expression of CD34; (7) frequent depletion of Y chromosome and complex changes of
      chromosomes; (8) positive for AML1/ETO fusion gene; (9) response well to
      chemotherapy regimen which simultaneously treated myeloid and lymphocytic
      leukemia. CONCLUSION: Abnormal expression of cCD79a/cCD22 in AML with t (8;21)
      (q22;q22) suggested that this kind of leukemia might be related with abnormal
      expression gene of B cell.

PMID- 16792935
TI  - [Antibiotic treatment for legionellosis].

PMID- 16792937
TI  - [Prevalence of coinfection by human immunodeficiency virus and hepatitis C virus
      in the Leon Health Area: 1992-2000].
AB  - OBJECTIVE: To ascertain the prevalence of HIV and hepatitis C (HCV) coinfection
      in the Health Area of Leon in the period of 1992 to 2000. PATIENTS, MATERIAL AND
      METHODS: The study included patients with HIV infection, residing for at least
      two years in the area, and attended at the Department of Internal Medicine of
      Leon Hospital. Sociodemographic information and risk behavior were recorded. Data
      from the Municipal Census of 1 May 1996 were used to calculate prevalence.
      Statistical analyses were carried out with the chi-square test or analysis of
      variance, according to the cases. RESULTS: The prevalence of HCV infection among
      HIV-positive patients was 56.8%. Coinfected men were younger than women and
      coinfection was higher in the parenteral transmission than in the sexual
      transmission groups. Prevalence was estimated at 53.2 cases per 100,000
      inhabitants of the Area (82.7 for men and 25.7 for women). The groups showing the
      highest prevalence were men aged 25-34 and 35-44 years. The epidemiology of the
      coinfection was mainly attributable to injected drug use. There was a decrease in
      the number of coinfection cases diagnosed during the study period. CONCLUSIONS:
      The prevalence of HIV/HCV coinfection in the Leon Health Area was lower than the
      rate estimated for Spain as a whole owing to a lower incidence of HIV infection
      and intravenous drug use. Nevertheless, HIV/HCV coinfection is a major public
      health problem, and resources should be allocated for its prevention and
      treatment.

PMID- 16792936
TI  - [Treatment for Legionnaires' disease. Macrolides or quinolones?].
AB  - BACKGROUND: Macrolides and fluoroquinolones are the recommended treatment for
      Legionnaires' disease. The aim of our study was to analyze the clinical efficacy
      of clarithromycin, azithromycin and levofloxacin in patients with Legionnaires'
      disease. METHODS: Prospective, observational study involving all adult patients
      with Legionella pneumophila pneumonia attended at Hospital Universitario Vall
      d'Hebron (Barcelona, Spain) from January 2001 to December 2004. Duration of
      fever, length of hospital stay and mortality were compared among 52 patients
      treated with clarithromycin, 43 with azithromycin and 18 with levofloxacin.
      RESULTS: The proportion of patients with risk factors for Legionnaires' disease,
      the initial severity of the pneumonia and the number of patients who required
      intensive care unit admission were similar in patients treated with
      clarithromycin, azithromycin and levofloxacin. In-hospital mortality was 5.3%.
      There were no significant differences in fever duration, length of hospital stay
      or mortality among the 3 groups of patients. CONCLUSION: In our experience,
      clarithromycin, azithromycin and levofloxacin were all efficacious for the
      treatment of Legionnaires' disease.

PMID- 16792938
TI  - A simple phenotypic method for differentiation between acquired and chromosomal
      AmpC beta-lactamases in Escherichia coli.
AB  - BACKGROUND: Screening methods for the detection of plasmid-mediated AmpC beta
      lactamases are technically demanding. The purpose of this study was to assess
      screening methods for the detection of these enzymes in clinical isolates of
      Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. METHODS: Isolates
      were selected according to a resistance phenotype consistent with production of
      an AmpC-type beta-lactamase. Detection of acquired ampC genes was done with a
      multiplex ampC-PCR and sequencing. The phenotypic detection methods evaluated
      included visual examination of antibiogram plates to identify the presence of
      scattered colonies located near the edge of the inhibition halo of cefoxitin,
      cefotaxime, ceftazidime and aztreonam, and a double-disc synergy test using
      cloxacillin (500 mg) to inhibit AmpC enzymes. RESULTS: Seventy-seven isolates
      were selected from among 6,209 isolates recovered. Acquired ampC genes (blaCMY-2,
      blaDHA-1, blaCMY-4 and blaACC-1) were found in 19 (24.7%) of these isolates,
      including 14 E. coli, two K. pneumoniae and three P. mirabilis isolates. The
      differential trait for the presence of colonies in the inhibition halo was 100%
      sensitive and specific. Similar results were obtained for the cloxacillin test,
      except for the E. coli isolates in which specificity was 10.3%. CONCLUSION: The
      phenotypic trait described here can be considered useful for suspecting the
      presence of these enzymes. The cloxacillin test was only useful in isolates
      lacking a natural AmpC beta-lactamase.

PMID- 16792940
TI  - [Streptococcus agalactiae infective endocarditis].
AB  - Streptococcus agalactiae infective endocarditis Streptococcus agalactiae is an
      unusual cause of infectious endocarditis. We describe the clinical
      characteristics, therapy and evolution of this infection in four patients
      diagnosed between 1996 and 2003. All four cases had native valve involvement and
      vegetations. All the patients had severe aortic failure and three of them also
      developed heart failure. Valve replacement surgery was performed in all four
      cases. Mortality was 50%. Infectious endocarditis due to S. agalactiae is very
      aggressive. Early surgery should be considered to prevent valve destruction and
      serious complications.

PMID- 16792939
TI  - [Impact of demographic and psychosocial factors on adherence to antiretroviral
      treatment].
AB  - BACKGROUND AND OBJECTIVE: Antiretroviral efficacy is closely related to the
      degree of adherence. The aim of this study is to assess the association between
      psychosocial and demographic variables and adherence to antiretroviral treatment.
      PATIENTS AND METHODS: A cross-sectional survey of 320 patients under
      antiretroviral treatment was conducted in four Andalusian hospitals, using a semi
      structured questionnaire given by health care professionals. RESULTS: Median age
      was 39.7 years. Nearly 12% of the sample was considered non-compliant to
      antiretroviral treatment. An interaction was observed between psychological
      morbidity and mental health quality of life scores. Among patients who presented
      psychological morbidity, a higher mental quality of life score was associated
      with a lower risk of non-compliance (P = 0.04). This association was not found
      among patients without psychological morbidity. Older age, homosexual or bisexual
      status and the use of injecting drugs for a shorter period of time was associated
      with non-compliance. CONCLUSIONS: Demographic and psychological factors have an
      influence on adherence to antiretroviral treatment.

PMID- 16792941
TI  - [HIV infection in patients aged 50 years or older in the HAART era].
AB  - There is little information on patients 50 years or older with HIV infection
      since the start of the HAART era. We performed a descriptive cross-sectional
      study during 2004 including 28 patients aged 52 to 87 years. Eighteen patients
      were men (64%) and sexual transmission was the risk factor in 23 (81%). Four
      patients (14%) fulfilled slow progression criteria and 13 (46%) belonged to the
      C3 category. Twenty-four patients were on HAART, with optimal adherence. All the
      patients were receiving HIV-unrelated medications to treat comorbid conditions.
      Hence, the profile of these patients is as follows: mainly male with sexually
      transmitted infection, severe immunodeficiency at the diagnosis, and frequent
      comorbid processes.

PMID- 16792942
TI  - [Robert Koch was right. Towards a new interpretation of tuberculin therapy].
AB  - At the centenary of Robert Koch's Nobel Prize award, tuberculosis treatment with
      tuberculin, which was announced in Berlin in 1890, is still considered a failure.
      Nevertheless, there is now sufficient information supporting the idea that
      tuberculin therapy was widely used until the second half of the twentieth
      century; thus, the impact of this treatment should be studied and related to the
      decrease in tuberculosis-related mortality recorded in that period. Moreover,
      tuberculin therapy has inspired at least two new immunotherapies; these, however,
      were directed toward precisely the opposite effect: suppression of the Koch
      phenomenon. Thus, inoculation of Mycobacterium vaccae polarizes the immune
      response towards the Th1 type; and inoculation of RUTI avoids local
      immunodepression after short-term chemotherapy without inducing toxicity. For
      this reason, Robert Koch's work on antituberculosis therapy should be reread and
      proper recognition given to his contribution in this field.

PMID- 16792943
TI  - [Hepatitis due to herpes group viruses].
AB  - In immunocompetent patients, primary infection by herpes simplex virus (HSV),
      varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6, and
      Epstein-Barr virus (EBV) generally produces mild, self-limited hepatitis. Primary
      infection by HSV in neonates and pregnant women, and infection by VZV in
      hematological and bone marrow recipients can cause fulminant hepatitis without
      characteristic skin lesions. In liver transplant recipients, hepatitis is the
      most common expression of CMV infection and the related symptoms are
      indistinguishable from those of acute rejection. Persistent hepatitis is a
      manifestation of the syndrome of active chronic infection by the EBV. Fulminating
      hepatitis due to herpes virus can be treated effectively if therapy is started
      early; hence, a high degree of clinical suspicion and inclusion of herpes virus
      in the differential diagnosis of this syndrome is necessary.

PMID- 16792944
TI  - [Lytic lesion in the tibia in a patient from Ecuador].

PMID- 16792945
TI  - [Spontaneous bacterial peritonitis in an ex-alcoholic elderly man].

PMID- 16792946
TI  - [A Nigerian-born woman presenting with vertebral ostelytic lesions].

PMID- 16792947
TI  - [Porin profile of P. aeruginosa forming biofilms on siliconized latex urinary
      catheters].

PMID- 16792948
TI  - [Murine typhus imported from Senegal in a travelling immigrant].

PMID- 16792949
TI  - [Clinical features of HIV infection in immigrants].

PMID- 16792950
TI  - [Comparison of two DNA extraction methods for the CMV quantification in blood].

PMID- 16792951
TI  - [Is cutting the nursing staff in the intensive care units justified?].

PMID- 16792952
TI  - [Analysis and recording of aggressions in the ICU].
AB  - The objectives of this study are to determine if aggressions occur by the family
      or patient against the nursing staff of the Intensive Care Units (ICU), identify
      if the aggressions received are recorded; specify if the nurses know about the
      existence of resources available by the hospital site and verify if the nurses
      understand aggression to be the same thing. We have conducted a descriptive study
      using a questionnaire done between November and December 2004 regarding
      aggressions suffered at work. The study sample includes 150 nurses who work in
      the ICU and Coronary Unit of the Hospital Universitario de Bellvitge (HUB).
      Inclusion criteria is the nursing staff of the ICU of HUB. The results of the
      surveys show that there are aggressions in the ICU (62% of those surveyed have
      been physically assaulted and 68% verbally). Most of these aggressions were only
      reported verbally (73% in verbal aggressions, 75% in physical aggressions), these
      hardly being recorded in written form (2.5% of those assaulted verbally and 40%
      of those assaulted physically). The conclusions of this study are that a high
      percentage of the ICU nurses have suffered aggressions in their work, with
      repercussions in their personal and work life. They normally comment the
      aggressions with colleagues or bosses, although they do not put it in writing.

PMID- 16792953
TI  - [Care work load in critical patients. Comparative study NEMS versus NAS].
AB  - INTRODUCTION: The systems of calculating care load have not yet reached the
      levels of generalized use which the systems of prognostic estimation of survival
      have. The reason for this is their potential defects of design (medical and not
      nursing conceptualization) and the sometimes confusing completion (TISS 76). The
      simplest ("nine equivalents of nurse manpower use score" [NEMS], care levels) add
      the difficulty of not being useful for the calculation of staff, because the
      design is not oriented towards nursing. The development of NAS (nursing activity
      score) by FRICE tries to solve all these problems. Our objective has been to
      verify to what degree the NEMS and NAS are correlated as systems of expression
      and calculation of care load. PATIENTS AND METHOD: During the last quarter of
      2004, NEMS and NAS have been used simultaneously by the nursing staff. During
      this period, 150 pairs of daily calculation values of NEMS-NAS and 150 pairs of
      calculation values by shift of NEMS-NAS have been collected. Comparison of means
      and linear correlation of values obtained and the analysis of the histograms of
      values of each series, their value ranges and analysis of their bias coefficients
      have been done. The analysis was done with the SPSS/PC 11. RESULTS: During the
      period indicated, it has been verified that NEMS has a much narrower value range
      than NAS, both in regards to daily values (18-45 versus 29.70-84.50) and in
      regards to values by shift (18-45 versus 22.40-84.50). The bias analysis shows a
      deviation to the left of both series of values. Linear correlation between NEMS
      NAS by shift shows a R2 of 0.1634 and becomes even poorer in the NEMS-NAS
      correlation per day with R2 of 0.2012. It should also be stressed that NEMS
      expresses its results in points while NAS does so in percentage of time occupied
      in the attention and care of the patient. CONCLUSIONS: In this preliminary study,
      the better adaptation of NAS versus NEMS to real work loads of patients
      hospitalized in the ICU and the non-possible correlation between the values of
      both systems is affirmed.

PMID- 16792956
TI  - [Asthma: protocols, guidelines and consensus statements. Which should be kept?].

PMID- 16792957
TI  - [Persistence of dengue in the tropics].

PMID- 16792958
TI  - [Dengue infection in children and adolescents in Panama].
AB  - BACKGROUND: Dengue is a serious emerging infectious disease and constitutes a
      major international health concern. MATERIAL AND METHODS: All reports of
      confirmed dengue infection in patients aged less than 18 years old between 2000
      and 2005 were included. A confirmed diagnosis was established by culture of the
      virus within the first 3 days of symptom onset or by serologic assays 5-30 days
      after symptom onset. Clinical and epidemiological features were analyzed.
      RESULTS: A total of 457 patients were included (57.6 % female). The median age
      was 13 years (IQR 5 6). A greater number of cases were detected in urban areas
      and during the rainy season (May-November). Two epidemics were reported in 2001
      (33.9 %) and the first eight months of 2005 (23.1 %). The most prevalent symptoms
      were fever (95.2 %), severe headache (74.2 %), chills (65.9 %), rash (63.5 %),
      myalgias (51.9 %) and retro-orbital pain (51.6 %). No significant differences
      were found between male and female patients. Significant differences in clinical
      features were found when the patients were divided into 3 groups; < 5 years old,
      6-10 years old and > 10 years old. Fifty-three percent of the patients had had
      previous contact with a dengue-infected individual. There were 7 patients with
      dengue hemorrhagic fever, 4 of whom died. CONCLUSIONS: Dengue virus infection is
      still a major health problem in Panama. To achieve effective control of dengue,
      further epidemiological studies, such as our own, are needed to design
      appropriate preventive measures.

PMID- 16792959
TI  - [Early indicators of dengue infection in children].
AB  - OBJECTIVE: To identify clinical manifestations and laboratory findings useful for
      the early diagnosis of dengue in children. MATERIALS AND METHODS: We
      prospectively evaluated 125 children (aged 5 to 12 years old) with acute febrile
      syndrome with no apparent etiology. Paired serologic tests and/or viral culture
      were performed and dengue infection was confirmed in 40 patients and ruled out in
      68 (17 indefinite cases). Early clinical manifestations (within the first 4 days
      of the disease) in the groups with dengue and other causes of febrile syndrome
      were compared. Independent indicators of dengue were determined in a multivariate
      logistic regression analysis. RESULTS: When clinical manifestations and complete
      blood count were considered, the independent indicators of dengue were: absence
      of nasal discharge, facial flushing, and leukocyte count < or = 4,500/.l. With at
      least two of these findings, a sensitivity of 67 % and a specificity of 72 % for
      the diagnosis of dengue were obtained. When coagulation tests were considered, a
      model for diagnosis was composed of: absence of nasal discharge, leukocyte count
      < or = 4500/.l, prothrombin time > 14 seconds, and partial thromboplastin time >
      29 seconds. Two of these findings suggested a diagnosis of dengue with a
      sensitivity of 90 % and a specificity of 52.9 %. With at least 3 findings,
      specificity increased to 89.7 % and sensitivity decreased to 50 %. The presence
      of the four components of this latter model shows a specificity of 100 %.
      CONCLUSIONS: Some clinical manifestations and simple laboratory tests could aid
      the early detection of dengue infection in children.

PMID- 16792960
TI  - [Burden of hospitalizations attributable to rotavirus infection in children in
      the Autonomous Region of Madrid, Spain, period 1999-2000].
AB  - OBJECTIVE: To assess rotavirus infection requiring hospitalization in children
      aged < or = 5 years between 1999 and 2000 in the Autonomous Region of Madrid
      (Spain). MATERIAL AND METHOD: A retrospective study was conducted, based on the
      hospital data surveillance system (Conjunto Minimo Basico de Datos [CMBD]) and on
      the Spanish national microbiological information system (Sistema de Informacion
      Microbiologica [SIM]). CMBD data for all hospital admissions in children aged <
      or = 5 years with a first-listed diagnosis of intestinal infectious disease (ICD
      9-CM codes: 001-009) or non-infective gastroenteritis (ICD-9-CM code: 558) and
      the reports to the SIM of the major pathogen groups responsible for acute
      gastroenteritis were analyzed. RESULTS: The annual incidence of hospitalizations
      for acute gastroenteritis was 69 cases per 10,000 children aged < or = 5 years.
      Fourteen percent of the 32,541 infections produced by pathogens responsible for
      acute gastroenteritis reported to the SIM were rotavirus. The estimated annual
      incidence of hospitalizations due to rotavirus infections was 12 cases per 10,000
      children aged (3/4) 5 years. The mean length of stay was 4.0 days, the annual
      mean number of days of hospitalization was 1,382 days, and the annual cost was
      565,907 J. During the rotavirus epidemic months (December and January), the
      percentage of excess hospitalizations was 67 %. CONCLUSIONS: Rotavirus causes a
      significant proportion of hospital admissions due to acute gastroenteritis in
      children aged < or = 5 years in the Autonomous Region of Madrid.

PMID- 16792961
TI  - [Psychiatric patients in the pediatric emergency department of a tertiary care
      center: review of a 6-month period].
AB  - INTRODUCTION: In the last few years, a marked increase in the number of
      psychiatric emergencies treated at pediatric emergency departments has been
      observed. The aim of the present study was to characterize these patients.
      PATIENTS AND METHODS: We performed a descriptive, prospective, cross sectional
      study, based on all psychiatric emergencies treated at the pediatric emergency
      department of Hospital General Universitario Gregorio Maranon, Madrid, from 1-10
      04 to 31-3-05. The following variables were analyzed: age, sex, time of
      consultation, day of the week, day of the month, month of the year, psychiatric
      antecedents, previous psychiatric pharmacologic treatment, the person or service
      who took the child to hospital, diagnosis, and whether the patient was admitted
      to the hospital. RESULTS: Of a total of 36,449 emergencies, 79 were psychiatric
      (0.21 %). Sex rates were 48.1 % boys and 51.9 % girls. The mean (+/-2 SD) age was
      13.73 +/- 2.5 years. Visits were most frequent on Mondays (19 %), in the evening,
      and in January and February. A total of 13.23 % of the patients were brought by
      extrahospital services. The main diagnoses were: behavioral disorders (36.76 %),
      anxiety disorders (20.58 %) and suicidal ideation or suicide attempt (13.23 %).
      There was a clear male predominance in behavioral disorders (67.85 %) and a
      female predominance in anxiety disorders (71.42 %) and suicidal ideation or
      suicide attempt (76.92 %). The hospitalization rate among these patients was
      32.35 %. CONCLUSIONS: The incidence of psychiatric disorders in our pediatric
      emergency department was low. The patients were aged 11-15 years old, without
      differences between the sexes. Peak demand was reached on Mondays in January and
      February, at the end of the evening and beginning of the night. The most common
      diagnosis was behavioral disorder. The hospitalization rate was exceptionally
      high, more than 6 times higher than the average in our hospital.

PMID- 16792962
TI  - [Ethical attitudes in Spanish pediatric critical care units].
AB  - OBJECTIVES: To assess physicians' awareness and experience of ethical problems
      that arise when dealing with critically ill children in pediatric intensive care
      units (PICUs). MATERIAL AND METHODS: Questionnaires containing 20 questions about
      ethical dilemmas and attitudes related to the care of children admitted to PICUs
      were mailed to 43 PICUs in Spain. RESULTS: Ninety-five responses corresponding to
      24 residents and 71 attending physicians were received from 21 PICUs. The
      occurrence of ethical dilemmas in the PICU was recognized by 96.8 % of the
      respondents. The most frequent method of solving these problems was through
      medical consensus (80 %), while family participation in the decision making
      process was highly variable. A total of 95.8 % of respondents stated that
      decisions to limit therapy were made in their PICU, although only one third of
      these decisions were written in the medical record. The most frequent form of
      therapeutic limitation was the do not resuscitate order. One third (32.6 %) of
      participants considered there were ethical differences between withdrawal and
      withholding of treatment. Attending physicians had greater experience of
      therapeutic limitation than did residents, but their opinions on the subject were
      similar. CONCLUSIONS: Ethical dilemmas are common in the PICU. In this setting,
      decisions about limitation of therapy are frequent, although many physicians
      admit to not being clear on this issue or on other aspects of clinical ethics.
      Family members' participation in the decision making process is insufficient in
      Spanish PICUs.

PMID- 16792963
TI  - [Perinatal outcomes in immigrant women].
AB  - OBJECTIVES: To describe the characteristics of immigrant women's newborns in our
      environment, and to compare them with those of native women's newborns. PATIENTS
      AND METHODS: All newborns attended in the Neonatology Section of Hospital del Mar
      in Barcelona, Spain, in 2003 and 2004 were included (n 5 2,735). Data were
      prospectively collected in a database. Pregnant immigrant women were classified
      in 6 regions (Eastern Europe, the rest of Europe, Africa, Asia, Latin America and
      other countries). Twelve diagnoses were defined and compared between native
      newborns and those of immigrant parents, and their relative risks were
      calculated. RESULTS: There were 1,296 native newborns (47.8 %) and 1,416 of
      immigrant origin (52.2 %). Immigrant women showed a higher rate of HBsAg carrier
      status (2.0 % versus 1.0 %) and a lower rate of hepatitis C virus infection (0.8
      % vs 2.0 %; p < 0.01). There was only one HIV-positive pregnant immigrant woman
      compared with 14 Spanish women (p < 0.01), and drug use was lower in the
      immigrant group (0.4 % vs 4.0 %; p < 0.01). Immigrant newborns had a lower rate
      of prematurity (6.0 % vs 7.6 %) and of low birthweight (2.3 % vs 4.6 %; p <
      0.01). There were no significant differences in the rate of respiratory distress
      or fetal acidosis. The incidence of neonatal infection risk was higher in
      immigrant newborns (49.9 % vs 40.6 %; p < 0.01). CONCLUSIONS: In our environment,
      immigrant mothers' newborns have better perinatal outcomes than native newborns.
      The most frequent complications are secondary to an inadequate.

PMID- 16792964
TI  - [Clinical practice guideline on asthma (part I)].

PMID- 16792965
TI  - [The role of the rotavirus vaccine in childhood vaccination schedules].
AB  - Rotavirus is the leading cause of diarrhea in infants. In developed countries,
      this infection leads to considerable morbidity with a high number of
      hospitalizations and medical interventions in the winter season, giving rise to
      substantial medical and social costs. In developing countries, rotavirus is a
      major cause of mortality in infants due to dehydration, with an estimated 600.000
      deaths or more per year worldwide. A vaccine that is easy administrated, safe and
      with high efficacy would be the ideal means to reduce the burden of this disease
      and its high economic and social cost and to decrease the number of deaths in low
      income countries. Recently, the results of two well-designed clinical trials with
      a large number of subjects have been reported. Both studies, which used different
      vaccines, reported high efficacy in the prevention of severe gastroenteritis and
      hospitalizations caused by rotavirus. When these vaccines become available in
      Europe, a reduction in hospitalizations, medical consultations, and days of work
      lost can be expected.

PMID- 16792966
TI  - [Holt-Oram syndrome: characterization of a novel mutation].
AB  - INTRODUCTION: Cardiomyelic syndromes encompass congenital heart disease and
      skeletal malformations of the upper limbs and are related to mutations in
      transcription factors with T-Box domains. Holt-Oram syndrome is caused by a
      dominant mutation in the TBX5 gene that alters the three-dimensional structure of
      the protein and its DNA binding function. Several point mutations and deletions
      in TBX5 have been reported in patients with the Holt-Oram syndrome phenotype.
      PATIENTS AND METHODS: The proband was a boy with a large atrial septal defect
      ostium secundum type and a ventricular septal defect, diagnosed by clinical
      findings (heart murmur) and echocardiography. He also presented slightly
      hypoplastic thumbs with distal bilateral placement and an implantation index of
      0.19 (compared with an average of 0.50 for his gestational age at birth). The boy
      was referred to the department of medical genetics to rule out 22q11.2
      microdeletion syndrome. RESULTS: Karyotype and fluorescence in situ hybridization
      at locus D22S75 were both normal. Because of his clinical findings, molecular
      study for Holt-Oram syndrome was indicated, leading to the finding of a mutation
      at intron 7 of TBX5, probably producing a splicing alteration of the gene and
      resulting in a protein truncated at its C-terminal end. The proband's parents
      presented the wild type sequence of the gene, thus indicating that the mutation
      was produced de novo, although a possible germinal mosaicism in the parents could
      not be ruled out. CONCLUSIONS: Holt-Oram syndrome is the most frequent cause of
      cardiomyelic syndrome. All children with heart malformations and abnormalities of
      the upper limbs such as absent, hypoplastic, distally placed or triphalangic
      thumbs should undergo molecular studies for this syndrome.

PMID- 16792967
TI  - [AIRE gene mutation in polyglandular syndrome type 1].
AB  - Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal recessive
      disorder characterized by chronic mucocutaneous candidiasis, autoimmune
      hypoparathyroidism, and primary adrenal insufficiency. It has recently been
      associated with mutations of a single gene found on chromosome 21, designated
      AutoImmune Regulator (AIRE). We report two patients with APS-1 referred to our
      hospital for evaluation. The first patient was an 11-year-old girl with
      hypoparathyroidism, infectious or immunological malabsorption, and autoimmune
      hepatitis. Hypoparathyroidism associated with other processes with a probable
      autoimmune origin suggested APS-1. Genetic study was performed revealing deletion
      of 13 base pairs in exon 8 of the AIRE gene. The second patient was a 17-year-old
      girl with autoimmune hepatitis, hypoparathyroidism, mucocutaneous candidiasis,
      nail dystrophy, and obliterating bronchiolitis with a probable autoimmune origin.
      We suspected APS-1 and genetic study was performed. The only finding was an AIRE
      gene polymorphism. In conclusion, the presence of a single disease criterion is
      sufficient to suspect APS-1 and to indicate genetic study. Further studies are
      required to confirm the involvement of other genes in the development of this
      disease.

PMID- 16792968
TI  - [Frey's syndrome: report of three cases with two distinct etiopathogeneses].
AB  - Frey's syndrome is characterized by recurrent episodes of facial gustatory
      flushing and sweating (most frequent in adults) limited to the cutaneous
      distribution of the auriculotemporal nerve which, when injured, shows abnormal
      regeneration. The condition is relatively common in adults following nerve injury
      in parotid surgery but has rarely been reported in children as a sequel of
      perinatal birth trauma resulting from forceps assisted delivery. We report three
      patients with the same syndrome and two different causes. Two children had a
      history of forceps assisted delivery and one adolescent had undergone
      preauricular lymphadenectomy. This syndrome, which has more often been described
      by allergists and maxillofacial surgeons than by pediatricians, may pose problems
      of differential diagnosis with food allergy, leading to unnecessary exclusion
      diets. In the pediatric age group, Frey's syndrome is self limiting and does not
      require therapy if the diagnosis is correct.

PMID- 16792970
TI  - [Frey's syndrome in childhood: a highly infrequent disease].

PMID- 16792969
TI  - [Gene as a cause of adrenal hypoplasia, hypogonadism and short height novel
      mutation of DAX-1 gene (pGly168fsX17)].
AB  - Various genes play a role in the morphogenesis of the adrenal cortex, among them
      the DAX-1 gene. We report an 18-year-old man who showed complete adrenal failure
      in the neonatal period, hypogonadotropic hypogonadism and pathological short
      stature associated with a mutation of the DAX-1 gene that has not previously been
      described. The patient was admitted to hospital at the age of 16 days due to salt
      losing syndrome with hyperpotassemia. After this episode, he received no
      treatment for 2 years, when he began to show progressive anorexia, salt avidity,
      asthenia, cutaneous hyperpigmentation and finally shock, with hypoglycemia,
      hyponatremia, metabolic acidosis and hyperpotassemia. Puberal development was
      spontaneous but incomplete. The patient received treatment with testosterone
      depot. He reached a definitive testicular volume of 6 ml and pubarche V. His
      final height is 150 cm (target height 164 cm). Amplification of the DAX-1 gene
      showed mutation g 2080-2081 insertion in the first position of codon 168, which
      produces a premature shutdown of protein DAX-1 at position 184.

PMID- 16792971
TI  - [Congenital errors of metabolism: a race of obstacles].

PMID- 16792972
TI  - [Enuresis associated with petit mal seizures].

PMID- 16792973
TI  - [Congenital ocular toxocariasis in a premature neonate].

PMID- 16792974
TI  - [Treatment with continuous subcutaneous insulin infusion in pediatric patients
      with type 1 diabetes mellitus].

PMID- 16792975
TI  - [Myelomalacia: a cause of delayed respiratory failure. Apropos of two cases].

PMID- 16792976
TI  - [Single-dose rasburicase as treatment for tumor lysis syndrome in two patients].

PMID- 16792977
TI  - [What is your diagnosis? A 3-month-old infant with a protruding ear].

PMID- 16792978
TI  - [Impact of immigration on drug resistance to Mycobacterium tuberculosis in
      Castellon (Spain): 1995-2003].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to know the frequency of
      resistant Mycobacterium tuberculosis in the province of Castellon (Spain) and to
      determine whether immigration is associated with resistance. MATERIAL AND METHOD:
      All culture-positive cases diagnosed in Castellon from January 1995 to December
      2003 were included in this retrospective study. Susceptibility tests were
      performed using the Canetti's proportion method and the MB/BacT system. Risk
      factors associated with tuberculosis were investigated in every case. RESULTS:
      Six hundred and forty-four cases of tuberculosis were studied: 560 were Spaniards
      and 84 foreigners. The overall frequency of resistant strains was 5%. The total
      rate of resistance in Spaniards was 3.7% and in foreigners 13.1%. In Spanish new
      cases, drug resistance was 3.2% and in foreigners new cases it was 13.9%. In
      previously treated cases, drug resistance was 6.7% in Spaniards and 0% in
      immigrants. No acquired drug resistance was detected in immigrants. Of those
      strains with resistance, 71.9% had resistance to only one drug, 18.7% to two
      drugs and 9.4% to more than two drugs. Multidrug-resistance was found in 9.4% of
      the resistant cases, and in 0.5% of all the studied population. The presence of
      resistant Mycobacterium tuberculosis was associated with the fact of having a
      foreign nationality (OR = 3.87; p < 0.001). CONCLUSIONS: Tuberculosis has been
      diminishing in Spanish patients in Castellon. Nevertheless, there is an important
      increase in the number of cases in foreigners, which is associated with a major
      percentage of resistances. Epidemiological vigilance efforts should especially
      concentrate on this group in order to support the progressive declivity of the
      disease.

PMID- 16792979
TI  - [Chlamydophila pneumoniae seroprevalence in adults from the general population].
AB  - BACKGROUND AND OBJECTIVE: Chlamydophila pneumoniae is an intracelular pathogen
      involved in the inflammatory pathogenesis of some chronic diseases with high
      prevalence. Infectivity is supposed to be high because the serologic patterns
      published are widely spread out all over the world. However, the prevalence in
      the Spanish adult population is unknown. Our goal was to assess the
      seroprevalence of specific IgG and IgA against C. pneumoniae in the general adult
      population performing an indirect immunofluorescence assay. MATERIAL AND METHOD:
      462 serum samples were analysed from subjects over 15 years of age in the general
      population in Valladolid. RESULTS: IgG 1:16 seroprevalence was 74.1% (95%
      confidence interval [CI], 69.7-78.6) and IgG 1:64 was 32.2% (95% CI, 27.6-36.8),
      whereas IgA 1:16 was 21.5% (95% CI, 17.7-25.4) and IgA 1:32 was 5.2% (95% CI, 3.3
      7.2). Higher titles were found in men and with increasing age, specially for IgA
      (p < 0.05). Only 3.6% (95% CI, 1.9-5.3) and 0.7% (95% CI, 0.03-1.4) of subjects
      showed titles IgG 1:256 or 1:512, respectively. Almost one fourth showed a title
      1:16 for both immunoglobulins. CONCLUSIONS: Chlamydophila pneumoniae maintains a
      high seroprevalence of infection in the Spanish adult population.

PMID- 16792980
TI  - [Analysis of Spanish hospital's reputation: relationship with their scientific
      production in different subspecialities].
AB  - BACKGROUND AND OBJECTIVE: To assess the relationship between reputation of
      hospitals, as determined by specialists' opinion, and their scientific
      production. MATERIAL AND METHOD: A questionnaire was sent to a sample of members
      of the Spanish Societies of Cardiology, Digestive Diseases, Neurology and
      Otorhinolaryngology. Each member had the possibility to nominate 5 hospitals with
      the greatest reputation amongst his/her specialty. Final score for those
      hospitals with more than 5% of all votes was used for the development of a
      reputation index. We assess the scientific production (number of publications and
      citations) for nominated hospitals and analyze the possible correlation between
      the reputation index and the scientific production. RESULTS: We received 151
      (30%) answers for cardiology, 227 (27%) for digestive diseases, 148 (30%) for
      neurology and 177 (18%) for otorhinolaryngology. The number of published articles
      and the number of citations for each nominated hospital showed a positive and
      statistically significant correlation with the reputation index. CONCLUSIONS:
      This is the first approach to analyze reputation parameters for Spanish
      hospitals. Scientific production and reputation index showed a positive
      correlation.

PMID- 16792981
TI  - [Mycobacterium tuberculosis and Homo sapiens: a long road to cross].

PMID- 16792982
TI  - [Medical errors in oncology and patient safety].

PMID- 16792983
TI  - [Cyclooxygenase-2: a new therapeutic target in atherosclerosis?].
AB  - It is now widely accepted that atherosclerosis is a complex chronic inflammatory
      disorder of the arterial tree associated with several risk factors. From the
      initial phases to eventual rupture of vulnerable atherosclerotic plaques, a low
      grade inflammation, also termed microinflammation, appears to play a key
      pathogenetic role. Systemic inflammatory markers (C reactive protein, cytokines
      adhesion molecules) also play a role in this process. Experimental and clinical
      evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the
      generation of prostaglandins from arachidonic acid, also contributes to lesion
      formation. Recent reports by our group have demonstrated increased monocyte COX-2
      activity and the production of prostaglandin E2 in relation to cardiovascular
      risk factors and subclinical atherosclerosis in asymptomatic subjects. Our
      findings support the notion that the COX-2/prostaglandin E2 axis may have a role,
      raising the question as to whether its selective inhibition might be an
      attractive therapeutic target in atherosclerosis. COX-2 inhibitors, collectively
      called "coxibs" (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a
      promise as anti-inflammatory drugs without the some of the side effects of
      aspirin or non steroidal antiinflammatory agents. However, clinical studies raise
      several clinically relevant questions as to their beneficial role in
      atherosclerosis prevention, because of increased thrombogenicity and
      cardiovascular risk, and therefore coxibs should be restricted in atherosclerosis
      prone patients.

PMID- 16792984
TI  - [Medico-legal autopsy].

PMID- 16792985
TI  - [Safety of antimigraine drugs during pregnancy].

PMID- 16792986
TI  - [Respiratory failure secondary to multiple pulmonary arteriovenous
      malformations].

PMID- 16792987
TI  - [Acute coronary syndrome caused by spontaneous coronary artery dissection].

PMID- 16792988
TI  - [Potential interaction between telitromicin and acenocumarol].

PMID- 16792989
TI  - [Acute poisoning caused by chicken meat consumption].

PMID- 16792990
TI  - [Spontaneous splenic rupture and Q fever].

PMID- 16792991
TI  - [Catheter-associated septic thrombophlebitis and arthritis due to penicillin
      resistant Streptococcus pneumoniae].

PMID- 16792992
TI  - Compatibility in the Biomphalaria glabrata/Echinostoma caproni model: Potential
      involvement of proteins from hemocytes revealed by a proteomic approach.
AB  - As an approach to investigate the suspected involvement of cellular factors in
      Biomphalaria glabrata resistance/susceptibility to Echinostoma caproni, we
      compared protein patterns from hemocytes collected from susceptible and resistant
      snails. This proteomic approach revealed that twelve hemocytic proteins exhibited
      significant differences in their apparent abundance. The genes corresponding to
      five of them were characterized by a combination of mass spectrometry and
      molecular cloning. They encode an aldolase, an intermediate filament protein, a
      cytidine deaminase, the ribosomal protein P1 and the histone H4. Furthermore, we
      investigated their expression in parasite-exposed or -unexposed snails. These
      last experiments revealed changes in transcript levels corresponding to
      intermediate filament and histone H4 proteins post-infection.

PMID- 16792993
TI  - The selective partitioning of the oligomers of polyethoxylated surfactant
      mixtures between interface and oil and water bulk phases.
AB  - Because their affinities for the oil and water phases vary considerably with the
      number of ethylene oxide units in their hydrophilic group, the ethoxylated
      nonionic species occurring in commercial products tend to behave in a non
      collective way, with the low ethoxylation oligomers partitioning mostly in the
      oil phase. This results in a surfactant mixture at the interface which is more
      hydrophilic than the one which was introduced in the system in the first place.
      The pseudophase model is used to study the partitioning in Winsor III type
      systems, and to estimate the deviation of the interfacial mixture composition
      from the overall one. New results indicate that the selective partitioning into
      the oil phase increases when the oil phase becomes aromatic, when the total
      surfactant concentration decreases and when the water-to-oil ratio decreases.

PMID- 16792994
TI  - Omega-3 fatty acids and decidual cell prostaglandin production in response to the
      inflammatory cytokine IL-1beta.
AB  - OBJECTIVE: The objective of this study was to determine the effect of omega-3
      fatty acids (eicosapentaenoic acid [EPA]; docosahexaenoic acid [DHA]) on
      prostaglandin production and prostanoid enzyme expression in cultured decidual
      cells exposed to interleukin-1beta (IL-1beta), a cytokine that plays a major role
      in inflammation. STUDY DESIGN: Decidua was obtained from human placentas of
      nonlaboring patients at term cesarean delivery (N = 6) and cultured by using
      standard cell culture techniques. Cells were preincubated in defined media with
      various concentrations of vehicle, DHA, or EPA for 1 hour. IL-1beta (10 ng/mL)
      was then added to the media, and experiments were terminated 12 hours after
      exposure to IL-1beta. Prostaglandin E2 (PGE2) and PGF2alpha concentrations in
      conditioned media were measured by enzyme-linked immunosorbent assay;
      cyclooxygenase-1 (COX-1), COX-2, microsomal prostaglandin E synthase (mPGES)-1,
      mPGES-2, and 15-hydroxy prostaglandin dehydrogenase (PGDH) expression were
      quantified by real-time polymerase chain reaction and immunoblotting. Groups were
      compared with the use of Student t test, with significance defined as P < .05.
      RESULTS: Preincubation with DHA decreased prostaglandin production by up to 80%
      when compared with controls. DHA decreased both mPGES-1 and -2 messenger RNA
      expression by approximately 50% (P = .02). Preincubation in DHA or EPA had no
      effect on COX-1, COX-2, and PGDH messenger RNA or protein expression. CONCLUSION:
      Under conditions simulating inflammation, supplementation with omega-3 fatty
      acids decreases PGE2 and PGF2alpha production in cultured decidual cells. The
      reduction in prostaglandin production was associated with a decreased expression
      of mPGES-1 and -2. These findings suggest a mechanism by which omega-3 fatty acid
      supplementation decreases the incidence of preterm birth in high-risk patients.

PMID- 16792995
TI  - Kinetic properties of wild-type and altered recombinant amidases by the use of
      ion-selective electrode assay method.
AB  - A novel assay method was investigated for wild-type and recombinant mutant
      amidases (EC 3.5.1.4) from Pseudomonas aeruginosa by ammonium ion-selective
      electrode (ISE). The initial velocity is proportional to the enzyme concentration
      by using the wild-type enzyme. The specific activities of the purified amidase
      were found to be 88.2 and 104.2 U mg protein(-1) for the linked assay and ISE
      methods, respectively. The kinetic constants--Vmax, Km, and Kcat--determined by
      Michaelis-Menten plot were 101.13 U mg protein(-1), 1.12x10(-2) M, and 64.04 s(
      1), respectively, for acrylamide as the substrate. On the other hand, the lower
      limit of detection and range of linearity of enzyme concentration were found to
      be 10.8 and 10.8 to 500 ng, respectively, for the linked assay method and 15.0
      and 15.0 to 15,000 ng, respectively, for the ISE method. Hydroxylamine was found
      to act as an uncompetitive activator of hydrolysis reaction catalyzed by amidase
      given that there is an increase in Vmax and Km when acetamide was used as the
      substrate. However, the effect of hydroxylamine on the hydrolysis reaction was
      dependent on the type of amidase and substrate involved in the reaction mixture.
      The degrees of activation (epsilon(a)) of the wild-type and mutant (T103I and
      C91A) enzymes were found to be 2.54, 12.63, and 4.33, respectively, for acetamide
      as the substrate. However, hydroxylamine did not activate the reaction catalyzed
      by wild-type and altered (C91A and W138G) amidases by using acrylamide and
      acetamide, respectively, as the substrate. The activating effect of hydroxylamine
      on the hydrolysis of acetamide, acrylamide, and p-nitrophenylacetamide can be
      explained by the fact that additional formation of ammonium ions occurred due to
      the transferase activity of amidases. However, the activating effect of
      hydroxylamine on the hydrolysis of p-nitroacetanilide may be due to a change in
      conformation of enzyme molecule. Therefore, the use of ISE permitted the study of
      the kinetic properties of wild-type and mutant amidases because it was possible
      to measure initial velocity of the enzyme-catalyzed reaction in real time.

PMID- 16792996
TI  - Commentary on: "Photosynthesis and negative entropy production" by Jennings and
      coworkers.
AB  - This commentary argues against the view that photochemical energy conversion
      violates the second law of thermodynamics, as expressed in a recent paper [R.C.
      Jennings, E. Engelmann, F. Garlaschi, A.P. Casazza, G. Zucchelli. Photosynthesis
      and negative entropy production. Biochim. Biophys. Acta 1709 (2005) 251-255]. The
      basic principles of free energy conversion by a photo-electrochemical cell are
      outlined, emphasizing the fact that the potential depends on the relative
      population of the excited state and thus on the illumination intensity.

PMID- 16792997
TI  - Nitric oxide and the respiratory enzyme.
AB  - Available information on the molecular mechanisms by which nitric oxide (NO)
      controls the activity of the respiratory enzyme (cytochrome-c-oxidase) is
      reviewed. We report that, depending on absolute electron flux, NO at
      physiological concentrations reversibly inhibits cytochrome-c-oxidase by two
      alternative reaction pathways, yielding either a nitrosyl- or a nitrite-heme a3
      derivative. We address a number of hypotheses, envisaging physiological and/or
      pathological effects of the reactions between NO and cytochrome-c-oxidase.

PMID- 16792998
TI  - Substrate specificity of a chimera made from Xenopus SGLT1-like protein and
      rabbit SGLT1.
AB  - To characterize the sugar translocation pathway of Na(+)/glucose cotransporter
      type 1 (SGLT1), a chimera was made by substituting the extracellular loop between
      transmembrane domain (TM) 12 and TM13 of Xenopus SGLT1-like protein (xSGLT1L)
      with the homologous region of rabbit SGLT1. The chimera was expressed in Xenopus
      oocytes and its transport activity was measured by the two-microelectrode voltage
      clamp method. The substrate specificity of the chimera was different from those
      of xSGLT1L and SGLT1. In addition the chimera's apparent Michaelis-Menten
      constant (K(m)) for myo-inositol, 0.06 mM, was about one fourth of that of
      xSGLT1L, 0.25 mM, while the chimera's apparent K(m) for d-glucose, 0.8 mM, was
      about one eighth of that of xSGLT1L, 6.3 mM. Our results suggest that the
      extracellular loop between TM12 and TM13 participates in the sugar transport of
      SGLT1.

PMID- 16792999
TI  - Cell-cycle-dependent variations in FTIR micro-spectra of single proliferating
      HeLa cells: principal component and artificial neural network analysis.
AB  - We have previously reported spectral differences for cells at different stages of
      the eukaryotic cell division cycle. These differences are due to the drastic
      biochemical and morphological changes that occur as a consequence of cell
      proliferation. We correlate these changes in FTIR absorption and Raman spectra of
      individual cells with their biochemical age (or phase in the cell cycle),
      determined by immunohistochemical staining to detect the appearance (and
      subsequent disappearance) of cell-cycle-specific cyclins, and/or the occurrence
      of DNA synthesis. Once spectra were correlated with their cells' staining
      patterns, we used methods of multivariate statistics to analyze the changes in
      cellular spectra as a function of cell cycle phase.

PMID- 16793000
TI  - Investigations of antimicrobial peptides in planar film systems.
AB  - Planar systems--monolayers and films--constitute a useful platform for studying
      membrane-active peptides. Here, we summarize varied approaches for studying
      peptide organization and peptide-lipid interactions at the air/water interface,
      and focus on three representative antimicrobial membrane--associated peptides
      alamethicin, gramicidin, and valinomycin. Experimental data, specifically surface
      pressure/area isotherms and Brewster angle microscopy images, provided
      information on peptide association and the effects of the lipid monolayers on
      peptide surface organization. In general, film analysis emphasized the effects of
      lipid layers in promoting peptide association and aggregation at the air/water
      interface. Importantly, the data demonstrated that in many cases peptide domains
      are phase-separated within the phospholipid monolayers, suggesting that this
      behavior contributes to the biological actions of membrane-active antimicrobial
      peptides.

PMID- 16793001
TI  - Sleeping with the enemy: clock monitoring in the maintenance of insomnia.
AB  - Two experiments that aimed to investigate the association between clock
      monitoring, pre-sleep worry and sleep are presented. In Experiment 1, 30 good and
      30 poor sleepers were instructed either to monitor or not to monitor a clock as
      they were trying to get to sleep. Worry was indexed by self-rating. Sleep was
      measured by self-report and actigraphy. Compared to non-monitors, clock-monitors
      reported more pre-sleep worry and they experienced longer sleep onset latency
      (SOL). These findings held true for both good and poor sleepers. In Experiment 2,
      following one night of baseline measurement, 38 individuals diagnosed with
      primary insomnia were instructed to monitor either a clock or a digit display
      unit (a control monitoring task) as they were trying to get to sleep. The clock
      monitoring task was rated to be more worry provoking and sleep interfering than
      the display unit-monitoring task. Whilst display unit-monitors experienced less
      pre-sleep worry, the clock-monitors experienced more pre-sleep worry and reported
      a longer SOL on the experimental night, relative to baseline. Further, compared
      to the display unit-monitors, the clock-monitors overestimated their SOL more on
      the experimental night. Together, these findings suggest that clock monitoring
      may trigger pre-sleep worry and serve to maintain insomnia by fuelling pre-sleep
      worry and exacerbating misperception of sleep.

PMID- 16793002
TI  - Phosphorylation of Thr654 but not Thr669 within the juxtamembrane domain of the
      EGF receptor inhibits calmodulin binding.
AB  - Calcium-calmodulin (CaM) binding to the epidermal growth factor receptor (EGFR)
      has been shown to both inhibit and stimulate receptor activity. CaM binds to the
      intracellular juxtamembrane (JM) domain (Met645-Phe688) of EGFR. Protein kinase C
      (PKC) mediated phosphorylation of Thr654 occurs within this domain. CaM binding
      to the JM domain inhibits PKC phosphorylation and conversely PKC mediated
      phosphorylation of Thr654 or Glu substitution of Thr654 inhibits CaM binding. A
      second threonine residue (Thr669) within the JM domain is phosphorylated by the
      mitogen-activated protein kinase (MAPK). Previous results have shown that CaM
      interferes with EGFR-induced MAPK activation. If and how phosphorylation of
      Thr669 affects CaM-EGFR interaction is however not known. In the present study we
      have used surface plasmon resonance (BIAcore) to study the influence of Thr669
      phosphorylation on real time interactions between the intracellular juxtamembrane
      (JM) domain of EGFR and CaM. The EGFR-JM was expressed as GST fusion proteins in
      Escherichia coli and phosphorylation was mimicked by generating Glu substitutions
      of either Thr654 or Thr669. Purified proteins were coupled to immobilized anti
      GST antibodies at the sensor surface and increasing concentration of CaM was
      applied. When mutating Thr654 to Glu654 no specific CaM binding could be
      detected. However, neither single substitutions of Thr669 (Gly669 or Glu669) nor
      double mutants Gly654/Gly669 or Gly654/Glu669 influenced the binding of CaM to
      the EGFR-JM. This clearly shows that PKC may regulate EGF-mediated CaM signalling
      through phosphorylation of Thr654 whereas phosphorylation of Thr669 seems to play
      a CaM independent regulatory role. The role of both residues in the EGFR
      calmodulin interaction was also studied in silico. Our modelling work supports a
      scenario where Thr654 from the JM domain interacts with Glu120 in the calmodulin
      molecule. Phosphorylation of Thr654 or Glu654 substitution creates a repulsive
      electrostatic force that would diminish CaM binding to the JM domain. These
      results are in line with the Biacore experiments showing a weak binding of the
      CaM to the JM domain with Thr654 mutated to Glu. Furthermore, these results
      provide a hypothesis to how CaM binding to EGFR might both positively and
      negatively interfere with EGFR-activity.

PMID- 16793003
TI  - Hepatocellular carcinoma model cell lines with two distinct migration modes.
AB  - Migration is an essential feature of metastatic cancer cells. To understand how
      motility is regulated in hepatocellular carcinoma, we analyzed gene expression
      profiles of mouse model cell lines we established from transgenic mice carrying
      SV40 large T antigen. A non-motile HC9 cell line was isolated from mouse liver
      tumors, and two additional cell lines, HCM1 and HCM4, were derived from HC9
      cells. We found that both HCM1 and HCM4 cells were substantially more migratory
      than HC9, and that HCM1 generated tumor nodules in nude mice. In contrast to HCM4
      cells that exhibited mesenchymal cell-type gene expression similar to HC9 cells,
      HCM1 cells appeared to have undergone a mesenchymal-amoeboidal transition. Thus,
      HCM1 and HCM4 cells have distinct migration and gene expression patterns, and
      together with HC9 cells, they can serve as model cell lines for understanding how
      migration is acquired and controlled in hepatocellular carcinoma.

PMID- 16793004
TI  - Crystal structure of a major fragment of the salt-tolerant glutaminase from
      Micrococcus luteus K-3.
AB  - Glutaminase of Micrococcus luteus K-3 (intact glutaminase; 48kDa) is digested to
      a C-terminally truncated fragment (glutaminase fragment; 42kDa) that shows higher
      salt tolerance than that of the intact glutaminase. The crystal structure of the
      glutaminase fragment was determined at 2.4A resolution using multiple-wavelength
      anomalous dispersion (MAD). The glutaminase fragment is composed of N-terminal
      and C-terminal domains, and a putative catalytic serine-lysine dyad (S64 and K67)
      is located in a cleft of the N-terminal domain. Mutations of the S64 or K67
      residues abolished the enzyme activity. The N-terminal domain has abundant
      glutamic acid residues on its surface, which may explain its salt-tolerant
      mechanism. A diffraction analysis of the intact glutaminase crystals (a twinning
      fraction of 0.43) located the glutaminase fragment in the unit cell but failed to
      turn up clear densities for the missing C-terminal portion of the molecule.

PMID- 16793005
TI  - A novel BLyS antagonist peptide designed based on the 3-D complex structure of
      BCMA and BLyS.
AB  - B lymphocyte stimulator (BLyS) is a member of tumor necrosis factor (TNF) family.
      Because of its roles in autoimmune diseases such as systemic lupus erythematosus
      (SLE), rheumatoid arthritis (RA), and Sjogren syndrome (SS), BLyS antagonists
      have been tested to treat SLE- and RA-like symptoms in mice and obtained
      optimistic results. So far, reported BLyS antagonists were mostly decoyed BLyS
      receptors or anti-BLyS antibodies. In this study, a novel BLyS antagonist
      peptide, PT, was designed based on the modeling 3-D complex structure of BCMA and
      BLyS. The interaction mode of PT with BLyS was analyzed theoretically. The
      results of competitive ELISA demonstrated that PT could inhibit the binding of
      BCMA-Fc and anti-BLyS antibody to BLyS in vitro. In addition, PT could partly
      block the proliferating activity of BLyS on mice splenocytes. The BLyS
      antagonizing activity of PT was significant (p<0.05). This study highlights the
      possibility of using BLyS antagonist peptide to neutralize BLyS activity. Further
      optimization of PT with computer-guided molecular design method to enhance its
      biopotency may be useful in developing new BLyS antagonists to treat BLyS-related
      autoimmune diseases.

PMID- 16793006
TI  - Characterization of ion channel and transporter mRNA expressions in isolated gill
      chloride and pavement cells of seawater acclimating eels.
AB  - Ion channels and transporters (i.e. cystic fibrosis transmembrane regulator
      (CFTR), inward rectifier potassium channel (eKir), Na/K-ATPase, Na/K/Cl2 co
      transporter (NKCC), aquaporin-3 (AQP-3), and Na/H exchanger-1 (NHE-1)) are known
      to be expressed in gill epithelia of teleost fish. Owing to the anatomical
      complexity of gill structures, their temporal expression profile in seawater
      acclimating gill pavement (PVCs) and chloride cells (CCs) are limited. In this
      study, we isolated the gill PVCs and CCs from seawater acclimating Japanese eels
      to address the issue. In the gill epithelia of freshwater adapted eels, CCs
      expressed the highest mRNA and/or protein levels of Na/K-ATPase, NKCC, and eKir
      as demonstrated by real-time PCR and/or immunohistochemical staining. AQP-3 mRNA
      was highly expressed in freshwater PVCs and its protein was in general expressed
      in all gill cells. The NHE-1 transcripts were expressed in similar levels in both
      PVCs and CCs. CFTR mRNA transcript was almost undetectable in all the freshwater
      gill cell samples. Seawater acclimation induced the transcript and/or protein
      levels of Na/K-ATPase, NKCC, CFTR, and eKir in CCs. The upregulation and the
      coexpression of these transporters in CCs suggested their cohort function in
      mediating Na+, K+, and Cl- transport. The expression of CFTR was found to be
      tightly regulated as its expression was restricted only in "seawater CCs". AQP-3
      transcript and protein levels in PVCs reduced significantly during the
      acclimation. Interestingly immunocytochemical (ICC) staining of seawater gill
      epithelia revealed that AQP-3 immunoreactivities were mainly localized in
      seawater CCs. In the acclimation, there was no significant reduction of NHE-1
      mRNA in both PVCs and CCs, however its protein level dropped significantly in the
      seawater condition. The present study is the first to demonstrate the activation
      of the mRNA transcripts for the ion channels and transporters in isolated gill
      CCs during seawater acclimation. The activating mechanism is found to be confined
      primarily in CCs. These results indicated that in addition to the increase in
      size and number of CCs, the molecular remodeling and the functional plasticity of
      CCs were essential in the ion transport process during seawater acclimation.

PMID- 16793007
TI  - Thiol regulation of vascular endothelial growth factor-A and its receptors in
      human retinal pigment epithelial cells.
AB  - We investigated the secretion and expression of VEGF-A and its receptors in human
      retinal pigment epithelial cells (RPE) under conditions of oxidative stress
      induced by glutathione (GSH) depletion. RPE cells were treated with 500 microM DL
      buthionine-(S,R)-sulfoximine (BSO) for varying times up to 24 h. Cellular GSH
      levels, GSH:GSSG ratios, VEGF-A mRNA and protein expression, as well as VEGF-A
      secretion, and VEGFR-1 and VEGFR-2 receptor expression were determined. Treatment
      with BSO caused a significant decrease in intracellular GSH and in GSH/GSSG
      ratios. Treatment with BSO increased VEGF-A mRNA linearly with time which was
      significant at 24h (p<0.01 vs untreated controls). An increase was also found for
      VEGF-A secretion with BSO treatment; incubation of RPE with GSH monoethyl ester
      (GSH-MEE) caused an 84% decrease in VEGF-A secretion. Further, thiol depletion by
      BSO caused a significant induction of VEGFR-1 and VEGFR-2. Thus, our studies show
      that cellular redox status plays an important role in VEGF regulation in RPE
      cells.

PMID- 16793008
TI  - Efficient amplification and cloning of near full-length hepatitis C virus genome
      from clinical samples.
AB  - Long RT-PCR (LRP) amplification of RNA templates is sometimes difficult compared
      to long PCR of DNA templates. Among RNA templates, hepatitis C virus (HCV)
      represents an excellent example to challenge the potential of LRP technology due
      to its extensive secondary structures and its difficulty to be readily cultured
      in vitro. The only source for viral genome amplification is clinical samples in
      which HCV is usually present at low titers. We have created a comprehensive
      optimization protocol that allows robust amplification of a 9.1 kb fragment of
      HCV, followed by efficient cloning into a novel vector. Detailed analyses
      indicate the lack of potential LRP-mediated recombination and the preservation of
      viral diversity. Thus, our LRP protocol could be applied for the amplification of
      other difficult RNA templates and may facilitate RNA virus research such as
      linked viral mutations and reverse genetics.

PMID- 16793009
TI  - Profile of rhythmic gene expression in the livers of obese diabetic KK-A(y) mice.
AB  - Although a number of genes expressed in most tissues, including the liver,
      exhibit circadian regulation, gene expression profiles are usually examined only
      at one scheduled time each day. In this study, we investigated the effects of
      obese diabetes on the hepatic mRNA levels of various genes at 6-h intervals over
      a single 24-h period. Microarray analysis revealed that many genes are expressed
      rhythmically, not only in control KK mice but also in obese diabetic KK-A(y)
      mice. Real-time quantitative PCR verified that 19 of 23 putative circadianly
      expressed genes showed significant 24-h rhythmicity in both strains. However,
      obese diabetes attenuated these expression rhythms in 10 of 19 genes. More
      importantly, the effects of obese diabetes were observed throughout the day in
      only two genes. These results suggest that observation time influences the
      results of gene expression analyses of genes expressed circadianly.

PMID- 16793010
TI  - Analysis of cag-8: a novel poly(Q)-encoding gene in the mouse brain.
AB  - We identified 13 transcript isoforms of a trinucleotide-repeat-containing gene,
      cag-8, that is expressed almost exclusively in the mouse brain. The polypeptide
      deduced from the cDNA consists of 137 AAs, of which 74 are glutamines. The 130-kb
      gene is composed of 16 exons, from which at least 13 isoforms with variable UTRs
      are formed by alternative splicing. A strong positive cis-acting element was
      found in the neuroblastomaxglioma hybrid NG108-15 and human embryonic kidney
      HEK293 cell lines. The cag-8 protein was localized in the cytosol and in granular
      bodies within the nucleus. These findings indicate that cag-8 is a novel poly(Q)
      encoding gene, the expression of which is confined primarily to the brain.

PMID- 16793011
TI  - Hormonal stimulation increases the recruitment of bone marrow-derived
      myoepithelial cells and periductal fibroblasts into the mammary gland.
AB  - Recent reports have revealed that bone marrow (BM)-derived cells can be
      constituents in a number of organs, especially in remodeling tissue. Using bone
      marrow transplantation (BMT) technique, we found that BM can serve as a source of
      both myoepithelial cells and periductal fibroblasts in the mammary gland. The
      numbers of BM-derived myoepithelial cell were 4.8-fold, and those of periductal
      fibroblast were 2.4-fold higher in the mice when BMT which was performed at the
      pubertal stage, as compared with BMT was performed at the postpubertal stage.
      Treatment with estrogen+progesterone pellet increased numbers of BM-derived
      myoepithelial cells and periductal fibroblasts, to levels 4.5- and 2.6-fold
      higher than in placebo mice, respectively. In situ hybridization revealed BM
      derived periductal fibroblasts expressed insulin-like growth factor I mRNAs that
      are known to regulate mammary gland. These results suggest that drastic
      structural change that is induced by hormonal stimulation increased the
      recruitment of BM-derived myoepithelial cells and periductal fibroblasts to the
      mammary gland context.

PMID- 16793012
TI  - Molecular and metabolic retinoid pathways in human amniotic membranes.
AB  - Vitamin A (retinol) and its active derivatives (the retinoids) are essential for
      the growth and development of the mammalian fetus and placenta. The amniotic
      membranes are extra-embryonic structures that are indispensable for normal
      gestation in mammals. Although placental involvement of retinoids is clearly
      established, little is known about the roles of retinoids for the associated
      amniotic membranes. The aim of this study was to define the metabolic and
      molecular pathways of retinoic signaling in human fetal membranes. The expression
      of retinoid receptors (RARalpha, beta and RXRalpha, beta) was established at
      transcript and protein levels. Enzymes involved in retinoic acid generation were
      also detected. The enzymatic generation of functional retinoids was confirmed
      using specific inhibitors of retinol metabolism. Finally, the functionality of
      retinoid pathways was demonstrated by inducing established retinoid target gene
      expression. Our results clearly demonstrated that the molecular and metabolic
      actors of retinoic signaling pathways are functional in human fetal membranes.

PMID- 16793013
TI  - alphaB-crystallin mutation in dilated cardiomyopathies: low prevalence in a
      consecutive series of 200 unrelated probands.

PMID- 16793015
TI  - WITHDRAWN: NF-kappaB is involved in early cellular response to mechanical stimuli
      in osteoblast-like cells in vitro.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 16793016
TI  - TRAIL-induced apoptosis proceeding from caspase-3-dependent and -independent
      pathways in distinct HeLa cells.
AB  - The apoptotic pathway in higher eukaryotes remains controversial with respect to
      the necessity of activation of caspase-3 in TRAIL (tumor necrosis factor-related
      apoptosis-inducing ligand)-treated cells. In this study, a fluorescence resonance
      energy transfer (FRET) probe was developed to image the activation of caspase-3
      and the related apoptotic pathway in TRAIL-treated cells in real time. Both kinds
      of apoptotic pathways were observed simultaneously in the same experiment
      proceeding from activation and non-activation of caspase-3. The total apoptotic
      rate was 56.08%, the apoptotic rates for activation and non-activation of caspase
      3 pathways were 21.5% and 34.58%, respectively, which were examined later for
      Hoechst 33258 staining and morphological characteristics. The apoptotic rate due
      to the activation of caspase-3 pathways in TRAIL-treated cells has been
      independently measured to be around 25.11% by capillary electrophoresis (CE)
      analysis, which confirmed the apoptotic rate due to activation of caspase-3
      pathways as found by FRET analysis. This result also suggests that rest apoptosis
      is preceded by caspase-3-independent pathways, as CE has the ability to
      quantitatively detect caspase-dependent apoptosis. The observation of the
      coexistence of caspase-3-dependent and caspase-3-independent apoptotic pathways
      in the TRAIL-treated cells was unusual in comparison with the previous reports.

PMID- 16793017
TI  - Binding of anti-prion agents to glycosaminoglycans: evidence from electronic
      absorption and circular dichroism spectroscopy.
AB  - The polyanionic glycosaminoglycans (GAGs) are intimately involved in the
      pathogenesis of protein conformational disorders such as amyloidosis and prion
      diseases. Several cationic agents are known to exhibit anti-prion activity but
      their mechanism of action is poorly understood. In this study, UV absorption and
      circular dichroism (CD) spectroscopic techniques were used to investigate the
      interaction between heparin and chondroitin-6-sulfate and anti-prion drugs
      including acridine, quinoline, and phenothiazine derivatives. UV band
      hypochromism of (+/-)-quinacrine, (+/-)-primaquine, tacrine, quinidine,
      chlorpromazine, and induced CD spectra of (+/-)-quinacrine upon addition of GAGs
      provided evidence for the GAG binding of these compounds. The association
      constants (approximately 10(6)-10(7)M(-1)) estimated from the UV titration curves
      show high-affinity drug-heparin interactions. Ionic strength-dependence of the
      absorption spectra suggested that the interaction between GAGs and the cationic
      drugs is principally electrostatic in nature. Drug binding differences of heparin
      and chondroitin-6-sulfate were attributed to their different negative charge
      density. These results call the attention to the alteration of GAG-prion/GAG
      amyloid interactions by which these compounds might exert their anti-prion/anti
      amyloidogenic activities.

PMID- 16793018
TI  - ZNF569, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling
      pathway.
AB  - Transcription factors play an essential role in altering gene expression. A great
      progress about transcription factors has been made towards the understanding of
      normal physiological processes, embryonic development, and human diseases. Here
      we report the identification and characterization of a novel KRAB-containing zinc
      finger protein, ZNF569, which is isolated from a human embryonic heart cDNA
      library. ZNF569 encodes a putative protein of 686 amino acids. The protein is
      conserved across different species during evolution. Expression of ZNF569 was
      found in most of the examined human adult and embryonic tissues with a higher
      level in heart and skeletal muscles. The KRAB and ZNF motifs of ZNF569 represent
      potent repression domains. When ZNF569 is fused to Gal-4 DNA-binding domain and
      co-transfected with VP-16, ZNF569 protein suppresses transcriptional activity.
      Overexpression of ZNF569 in COS-7 cells inhibited the transcriptional activities
      of SRE and AP-1, which may be silenced by siRNA. The results suggest that ZNF569
      protein may act as a transcriptional repressor that suppresses MAPK signaling
      pathway to mediate cellular functions.

PMID- 16793019
TI  - PAF-receptor is preferentially expressed in a distinct synthetic phenotype of
      smooth muscle cells cloned from human internal thoracic artery: functional
      implications in cell migration.
AB  - Platelet-activating-Factor (PAF) and its structural analogues formed upon low
      density lipoprotein oxidation are involved in atherosclerotic plaque formation
      and may signal through PAF-receptor (PAF-R) expressed in human macrophages and in
      certain smooth muscle cells (SMCs) in the media, but rarely in the intima of
      human plaques. Our aim was to determine which SMC phenotype expresses PAF-R and
      whether this receptor is functional in cell migration. Circulating SMC
      progenitors and two phenotypically distinct clones of proliferative, epithelioid
      phenotype vs contractile, spindle-shaped SMCs from the media of adult internal
      thoracic artery were studied for the presence of PAF-receptor (PAF-R). The levels
      of specific mRNA were obtained by reverse transcription/real-time PCR, the
      protein expression was deduced from immunohistochemistry staining, and the
      functional transmigration assay was performed by Boyden chamber-type chemotaxis
      assay. Only SMCs of spindle-shape and synthetic phenotype expressed both mRNA and
      PAF-R protein and in the functional test migrated at low concentrations of PAF.
      Two unrelated, specific PAF-R antagonists inhibited PAF-induced migration, but
      did not modify the migration initiated by PDGF. The presence of functional PAF-R
      in arterial spindle-shaped SMCs of synthetic phenotype may be important for their
      migration from the media into the intima and atherosclerotic plaques formation.

PMID- 16793020
TI  - A novel siRNA validation system for functional screening and identification of
      effective RNAi probes in mammalian cells.
AB  - Small interfering RNAs (siRNAs) have become the most powerful and widely used
      gene silencing reagents for reverse functional genomics and molecular
      therapeutics. The key challenge for achieving effective gene silencing in
      particular for the purpose of the therapeutics is primarily dependent on the
      effectiveness and specificity of the RNAi targeting sequence. However, only a
      limited number of siRNAs is capable of inducing highly effective and sequence
      specific gene silencing by RNA interference (RNAi) mechanism. In addition, the
      efficacy of siRNA-induced gene silencing can only be experimentally measured
      based on inhibition of the target gene expression. Therefore, it is important to
      establish a fully robust and comparative validating system for determining the
      efficacy of designed siRNAs. In this study, we have developed a reliable and
      quantitative reporter-based siRNA validation system that consists of a short
      synthetic DNA fragment containing an RNAi targeting sequence of interest and two
      expression vectors for targeting reporter and triggering siRNA expression. The
      efficacy of the siRNAs is measured by their abilities to inhibit expression of
      the targeting reporter gene with easily quantified readouts including enhanced
      green fluorescence protein (EGFP) and firefly luciferase. Using fully analyzed
      siRNAs against human hepatitis B virus (HBV) surface antigen (HBsAg) and tumor
      suppressor protein p53, we have demonstrated that this system could effectively
      and faithfully report the efficacy of the corresponding siRNAs. In addition, we
      have further applied this system for screening and identification of the highly
      effective siRNAs that could specifically inhibit expression of mouse matrix
      metalloproteinase-7 (MMP-7), Epstein-Barr virus (EBV) latent membrane protein 1
      (LMP1), and human serine/threonine kinase AKT1. Since only a readily available
      short synthetic DNA fragment is needed for constructing this novel reporter-based
      siRNA validation system, this system not only provides a powerful strategy for
      screening highly effective siRNAs but also implicates in the use of RNAi for
      studying novel gene function in mammals.

PMID- 16793021
TI  - Shear stress induces endothelial transdifferentiation from mouse smooth muscle
      cells.
AB  - Smooth muscle cells (SMCs) under shear stress may alter their gene expression
      patterns to adapt to a new hemodynamic environment. Their plasticity may play an
      important role in vascular development, healing, and remodeling as well as
      vascular lesion formation under abnormal environmental conditions. A mouse
      vascular SMC line (P53LMACO1) cultured under shear stress significantly increased
      the mRNA levels of endothelial cell markers including Platelet-endothelial cell
      adhesion molecule-1 (PECAM-1), von Willebrand factor (vWF), and VE-cadherin,
      while significantly decreasing the mRNA levels of SMC markers including alpha
      smooth muscle actin (alpha-SMA), calponin-1, smooth muscle myosin heavy chain
      (SMMHC), and transgelin as compared to static control cells. Protein levels of
      PECAM-1 and vWF were significantly increased, while protein levels of alpha-SMA
      were substantially decreased in the shear stress-cultured cells. In addition,
      shear stress-cultured cells showed an enhanced capability to form capillary-like
      structures on Matrigel. Thus, shear stress may promote endothelial cell
      transdifferentiation from SMCs.

PMID- 16793022
TI  - Azaspiracids modulate intracellular pH levels in human lymphocytes.
AB  - The azaspiracids (AZAs) are a group of marine toxins implicated in several
      intoxications whose mechanism of action is unknown. These phycotoxins include the
      five compounds shown in : AZA-1 (1), AZA-2 (2), AZA-3 (3), AZA-4 (4), and AZA-5
      (5). The aim of this work was to study the effects of the five naturally
      occurring azaspiracids (AZA-1 to -5, Fig. 1) and four synthetic analogues (6-9,
      Fig. 2) on intracellular pH, and the influence of Ca2+ upon this effect. The AZAs
      (1-5) were found to modulate cytosolic Ca2+ levels in human lymphocytes, while
      some of them, but not all, had effects on the intracellular pH. AZA-1 (1) and AZA
      2 (2) did not modify intracellular pH in a Ca2+-containing or a Ca2+-free medium.
      AZA-3 (3) increased intracellular pH by 0.16 units in the presence of
      extracellular Ca2+, an effect that was blocked when a 1 mM solution of Ni2+ was
      added. In a Ca2+-free medium, the increase in pH induced by AZA-3 (3) was reduced
      to 0.08 pH units. AZA-4 (4) inhibited the basal pH increase even in the presence
      of a 1 mM solution of Ni2+. In a Ca2+-free medium, the inhibition caused by AZA-4
      (4) was small, but when Ca2+ was added back to the medium, the pH basal increase
      was again significantly inhibited. The alkalinization was also inhibited when AZA
      4 (4) was added simultaneously, 10 min before or 10 min after thapsigargin (Tg),
      and also when the Ca2+-influx induced by Tg was inhibited by Ni2+. AZA-5 (5), on
      the other hand, did not modulate the intracellular pH profile in either a Ca2+
      containing or a Ca2+-free medium. Finally, we investigated four synthetic
      analogues (6-9, Fig. 2) whose structures were based on the four originally
      proposed structures of azaspiracid-1, with an opened E-ring. Compound 6 induced a
      small cytosolic Ca2+ increase, but did not modify intracellular pH in saline
      solution. In a Ca2+-free medium, compound 6 blocked the pH fall when Ca2+ was
      added back to the medium. Compound 7 also did not modify intracellular pH in
      saline solutions, however it significantly blocked basal pH increases in a Ca2+
      free medium. Compound 8 did not alter intracellular pH, however compound 9
      induced a small acidification when Ca2+ was present in the extracellular medium.
      These results point to a structure-activity relationship in AZAs pH effect that
      affects the modulation and the coupling of intracellular pH and Ca2+.

PMID- 16793023
TI  - The angiosuppressive effects of 20(R)- ginsenoside Rg3.
AB  - Aberrant angiogenesis is an essential step for the progression of solid tumors.
      Thus anti-angiogenic therapy is one of the most promising approaches to control
      tumor growth. In this study, we examined the ability of 20(R)-ginsenoside Rg3
      (Rg3), one of the active compounds present in ginseng root, to interfere with the
      various steps of angiogenesis. Rg3 was found to inhibit the proliferation of
      human umbilical vein endothelial cells (HUVEC) with an IC50 of 10 nM in Trypan
      blue exclusion assay. Rg3 (1-10(3) nM) also dose dependently suppressed the
      capillary tube formation of HUVEC on the Matrigel in the presence or absence of
      20 ng/ml vascular endothelial growth factor (VEGF). The VEGF-induced
      chemoinvasion of HUVEC and ex vivo microvascular sprouting in rat aortic ring
      assay were both significantly attenuated by Rg3. In addition, Rg3 (150 and 600
      nM) remarkably abolished the basic fibroblast growth factor (bFGF)-induced
      angiogenesis in an in vivo Matrigel plug assay. The Matrix metalloproteinases
      (MMPs), such as MMP-2 and MMP-9, which play an important role in the degradation
      of basement membrane in angiogenesis and tumor metastasis present in the culture
      supernatant of Rg3-treated aortic ring culture were found to decrease in their
      gelatinolytic activities. Taken together, these data underpin the anti-tumor
      property of Rg3 through its angiosuppressive activity.

PMID- 16793024
TI  - Electroacupuncture modulates cortical activities evoked by noxious somatosensory
      stimulations in human.
AB  - A noninvasive high-resolution imaging technique of cerebral electric activities
      has been developed to directly link scalp potential measurement with the magnetic
      resonance images of the subjects, which is very helpful for the elucidation of
      the cortical processing following various stimulations. Here, we used a 64
      channel Neuroscan ESI-128 system to explore the specific cortical activities
      elicited by electroacupuncture (EA) acupoint in normal volunteers and the
      modulatory effect of EA on cortical activities evoked by noxious somatosensory
      stimulation. A specific later-latency somatosensory-evoked potential (SEP, P150)
      located in bilateral anterior cingulated cortex was observed after EA acupoint
      but not non-acupoint. Two pain-specific SEP components (P170 and N280), located
      in bilateral suprasylvian operculum and anterior cingulated cortex respectively
      were observed following painful median nerve stimulation. Binding EA acupoint
      with painful median nerve stimulation, the amplitudes of P170 and N280 appeared
      to be attenuated significantly, 2D topography exhibited tremendous decrease of
      cortical activation between 120 ms and 296 ms in latency, and visual analogue
      scale (VAS) changes also showed a similar pattern to the change of amplitude. The
      bilateral anterior cingulated cortex recruited following acupoint stimuli might,
      to some extent, suggest that EA has the specific physiological effects. Decrease
      of pain-induced cortical activation by EA acupoint was considered to be mainly
      due to an interaction of the signals in anterior cingulated cortex ascending from
      the pain stimulation and EA.

PMID- 16793025
TI  - Immunohistochemical labeling of the mu opioid receptor carboxy terminal splice
      variant mMOR-1B4 in the mouse central nervous system.
AB  - The mu opioid receptor gene Oprm is alternatively spliced into many variants,
      providing for the multiplicity of mu opioid receptor subtypes. One of the mouse
      variants, mMOR-1B4, is unique in that it displays high affinity towards a wide
      range of mu opioid receptor antagonists, but poor affinity towards most classical
      mu opioid agonists. The present study examined the immunohistochemical
      distribution of the mMOR-1B4 variant in mouse brain and spinal cord. mMOR-1B4
      like immunoreactivity (mMOR-1B4-LI) was enriched in many regions of the brain,
      spinal cord and in the dorsal root ganglia. Some of the structures showing
      prominent mMOR-1B4-LI include the olfactory bulb, cerebral cortex, bed nucleus of
      stria terminalis, hippocampus, habenular nucleus, amygdala, thalamus,
      hypothalamus, medium eminence, substantia nigra, ventral tegmental area,
      oculomotor nucleus, red nucleus, raphe nuclei, periaqueductal gray, locus
      coeruleus, trigeminal nucleus, reticular formation, area postrema and Purkinje
      cell layer and deep nuclei of cerebellum. mMOR-1B4-LI was present in afferent
      neurons of the dorsal root ganglia and their projecting fibers into the
      superficial laminae of the spinal dorsal horn. Some motor neurons in the anterior
      horn of the spinal cord also were immunopositive. The overall distribution of
      mMOR-1B4-LI in the central nervous system is distinguishable from previously
      characterized variants such as MOR-1-LI, MOR-1C-LI and exon-11-LI. These studies
      provide evidence for the region- and neuron-specific processing of the Oprm gene
      and support the possibility of functional differences among the variants.

PMID- 16793026
TI  - Progestins inhibit the neuroprotective effects of estrogen in rat hippocampus.
AB  - Although estrogen has beneficial actions in brain, recent clinical trials
      demonstrated adverse neural effects of hormone therapy in postmenopausal women.
      The cause(s) of this disconnect between experimental and clinical findings may
      include unanticipated effects of progestins. We report that both natural
      progesterone and the clinical progestin medroxyprogesterone acetate block
      estrogen neuroprotection. These findings underscore the need to evaluate neural
      actions of progestins in the rational design of hormone therapy.

PMID- 16793027
TI  - Effects of NOS inhibition on the cardiopulmonary system and brain microvascular
      markers after intermittent hypoxia in rats.
AB  - We previously demonstrated that rats subjected to intermittent hypoxia (IH) by
      exposure to 10% O(2) for 4 h daily for 56 days in a normobaric chamber, developed
      pulmonary hypertension, right ventricular hypertrophy and wall-thickening in
      pulmonary arterioles, compared with normoxic (N) controls. These changes were
      greater in rats subjected to continuous hypoxia (CH breathing 10% O(2) for 56
      days). Cerebral angiogenesis was demonstrated by immunostaining with glucose
      transporter 1 (GLUT1) antibody, in viable vessels, in CH and to a lesser degree
      in IH. In this study, adult Wistar rats were subjected to the same hypoxic
      regimes and given the nitric oxide synthase (NOS) inhibitor N(6)-nitro-L-arginine
      methyl ester (L-NAME) in drinking water (NLN, IHLN and CHLN regimes) to induce
      hypertension. There was significant systemic hypertension in NLN and IHLN rats,
      compared with N and IH, but surprisingly not in CHLN compared with CH. Hematocrit
      rose in all hypoxic groups (up to 79% in CHLN). There was no significant
      pulmonary hypertension in IHLN versus NLN rats, although there was asymmetric
      wall thickening in pulmonary arterioles. Cerebral GLUT1 immunoreactivity
      increased with L-NAME, with or without hypoxia, especially in CHLN rats, but
      conspicuously there was no evidence of angiogenesis in brains of IHLN compared
      with NLN rats. NOS blockade may attenuate the cerebral and pulmonary vascular
      changes of IH while augmenting cerebral angiogenesis in continuous hypoxia.
      However, whether cerebral effects are due to systemic hypertension or changes in
      cerebral nitric oxide production needs to be evaluated.

PMID- 16793028
TI  - Changes in concentration of cerebrospinal fluid components in patients with
      traumatic brain injury.
AB  - Brain injury, like other central nervous system pathologies, causes changes in
      the composition of the cerebrospinal fluid (CSF). In this study, changes in the
      concentration of small molecules of the CSF, which are in the minimal micromolar
      concentration, were observed and monitored using high-resolution proton (NMR)
      spectroscopy. Twenty-two patients with isolated traumatic brain injuries (TBI)
      and 15 patients making up the control group were recruited for the study. CSF
      samples were collected by lumbar puncture from the lumbar subarachnoid space in
      the patients just before commencement of therapy and on the first, third, seventh
      and fourteenth days of therapy at the ICU. Forty-four signals of the NMR spectra
      and NO concentration of the CSF samples were analyzed. The analysis shows that
      the amino acid and organic acid concentrations change during the therapy and
      mostly are higher than in the control group. Significant differences in
      concentration of the analyzed CSF components between the TBI patients and the
      control group have been noted. The rate of the lactate to pyruvate conversion
      increased because the L/P ratio showed no significant differences between the TBI
      group and the control group, while the concentrations of both components were
      significantly higher in the TBI patients than in the control group. Citrulline,
      arginine and nitric oxide concentrations were the focus of the analysis.
      Citrulline concentration changes overlapped NO changes from 0 until 3rd day of
      therapy, while for the remaining days of observation the NO concentration
      stabilized at the control level, whereas citrulline concentration significantly
      decreased.

PMID- 16793029
TI  - Abnormal mGluR2/3 expression in the perforant path termination zones and mossy
      fibers of chronically epileptic rats.
AB  - Epilepsy is characterized by hyperexcitability of hippocampal networks, excessive
      release of glutamate, and progressive neurodegeneration. Presynaptic group II
      metabotropic receptors (mGluR2 and mGluR3) are among different mechanisms that
      modulate presynaptic release of glutamate, especially at the mossy fibers in the
      hippocampus. Here, we explore whether mGluR2/3 expression is affected in a rat
      model of temporal lobe epilepsy obtained via pilocarpine-induced status
      epilepticus (SE). Immunohistochemical assays were performed in age-matched
      controls and two groups of epileptic rats sacrificed at 25-35 days (1 month post
      SE) and at 55-65 days (2 months post-SE) following SE onset. A dramatic lessening
      of mGluR2/3 immunofluorescence was observed at CA1 and CA3 stratum
      lacunosum/molecular (SLM) declining to 60% and 68% of control values in 1-month
      and 2-month post-SE, respectively. Additionally, thickness of mGluR2/3-stained
      SLM layer narrowed up to 70% of controls indicating atrophy at this branch of the
      perforant path. Epileptic rats exhibited a marked and progressive down-regulation
      of mGluR2/3 expression in mossy fiber at hilus and CA3 stratum lucidum in
      contrast with an enhanced expression of vesicular glutamate transporter type 1
      (VGluT1) at the mossy fibers. Intense VGluT1 punctated staining was detected at
      the inner third molecular layer indicating glutamatergic sprouting. In the
      molecular layer, mGluR2/3 labeling slightly declined in the 1-month post-SE group
      but then increased in the 2-month post-SE group although it was diffusely
      distributed. Down-regulation of mGluR2/3 at the mossy fibers and the SLM may
      render epileptic hippocampal networks hyperexcitable and susceptible to glutamate
      mediated excitotoxicity and neurodegeneration.

PMID- 16793030
TI  - Dorsal hindbrain 5-HT3 receptors participate in control of meal size and mediate
      CCK-induced satiation.
AB  - We have previously shown that systemic administration of ondansetron, a selective
      serotonin type-3 (5-HT3) receptor antagonist, attenuates cholecystokinin (CCK)
      induced suppression of food intake. The exact location of 5-HT3 receptors
      mediating this action is not clear and may involve hindbrain 5-HT3 receptors. In
      this study, we first examined sucrose intake in response to direct injections of
      ondansetron into various sites of the dorsal hindbrain. Ondansetron (1.0 and 2.0
      microg/100 nl) delivered into the medial nucleus of the solitary tract (NTS)
      significantly increased 15% sucrose intake (12.2 +/- 0.6 and 13.5 +/- 0.7 ml,
      respectively) compared to control (10.2 +/- 0.7 ml), while equivalent injections
      into ipsilateral adjacent sites such as the lateral NTS, dorsal medial nucleus of
      the vagus, and other areas of the dorsal hindbrain had no effect on sucrose
      intake. Second, we examined the effects of hindbrain 5-HT3 receptor blockade on
      suppression of intake by systemic CCK. Fourth ventricular (i.c.v.) administration
      of ondansetron (10.0 microg/3.0 microl) significantly attenuated suppression of
      intake by CCK (9.1 +/- 1.0 vs. 6.4 +/- 0.4 ml, respectively). Ondansetron alone
      had no effect on sucrose intake at any i.c.v. dose tested. In a separate group of
      rats, CCK administration suppressed 60-min intake significantly (8.9 +/- 0.8 ml)
      compared to control (12.4 +/- 0.4 ml). Administration of ondansetron into the
      medial NTS completely reversed suppression of intake by CCK (11.8 +/- 1.0 and
      12.3 +/- 1.4 ml, for 0.5 microg and 1.0 microg/100 nl, respectively). These data
      demonstrate that 5-HT3 receptors located in the medial NTS participate in control
      of meal size and mediate CCK-induced suppression of food intake.

PMID- 16793031
TI  - Study of the adenosinergic system in the brain of HPRT knockout mouse (Lesch
      Nyhan disease).
AB  - BACKGROUND: Lesch-Nyhan disease (LND), an X-linked genetic disease caused by
      complete deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase
      (HPRT), is characterized by hyperuricemia and psychiatric disturbance, mainly
      self-aggressiveness. Literature dates support the hypothesis that dopaminergic
      deficit and serotonergic excess in the circuit of basal ganglia are responsible
      for the aggressive behavior. Altered adenosine transport across the membrane of
      HPRT-deficient lymphocytes has been reported, suggesting adenosine involvement in
      LND. METHODS: The expression of several genes related to the adenosinergic system
      (ADORA1A, ADORA2A, ADORA2B) were studied in the brain of the murine model of LND
      by real time PCR. Nucleotide levels and enzyme activities possibly involved in
      adenosine release were also measured. RESULTS: Studies performed by real time PCR
      showed 95% increase in ADORA1A expression, 15% decrease in ADORA2A expression,
      and no change in ADORA2B expression in knockout mice compared to controls. No
      significant differences were found in the level of nucleotides or enzyme
      activities between control and mutant mice. CONCLUSIONS: Our results suggest that
      adenosine neurotransmission might be involved in the specific neurobehavioral
      features of LND by increased expression of adenosine A1 receptors.

PMID- 16793033
TI  - Granulometric analysis of corneal endothelium specular images by using a germ
      grain model.
AB  - Specular microscopy is widely used to study the human corneal endothelium status
      in vivo. In this paper, the corneal endothelium is represented as a binary image
      composed of the cell inscribed circles. The granulometric distribution function
      of the complement of this image is used as a functional descriptor, which
      provides information about the shape, size and spatial arrangement of cells.
      Experimental evaluation using bootstrap techniques shows its ability to
      discriminate between controls and pathological cases. It represents a reliable
      and graphical alternative to the classical indices (cell density, hexagonality
      and coefficient of variation of cell areas), which behave poorly when detecting
      subtle abnormalities.

PMID- 16793032
TI  - Pro-inflammatory states and IGF-I level in ischemic heart disease with low or
      high serum iron.
AB  - BACKGROUND: Serum iron overload or iron deficiency appears to be associated with
      atherosclerosis and ischemic myocardial damage. Roles of low or high serum iron
      in patients with ischemic heart diseases are still controversial. METHODS: Serum
      samples for biochemical and immunologic analyses were collected from the 73
      normal subjects and the 90 patients with ischemic heart disease (IHD), the latter
      of which were selected from 142 patients and classified by low, normal and high
      serum iron. RESULTS: Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL
      6), high sensitive C-Reactive protein (hsCRP), and interleukin-10 (IL-10) were
      increased and insulin-like growth factor (IGF)-I was decreased in IHD patients
      with low serum iron, whereas these parameters were not changed in IHD patients
      with normal or high serum iron, compared with normal subjects. Total bilirubin
      was increased in IHD patients with high serum iron but was not changed in IHD
      patients with low or normal serum iron, compared with normal subjects.
      CONCLUSION: The IHD patients with low serum iron were associated with a pro
      inflammatory state, such as increased TNF-alpha, IL-6, and hsCRP; increased anti
      inflammatory activities, such as increased IL-10; decreased cardiac protective
      factor, such as decreased IGF-I. These findings may imply that IHD patients with
      low serum irons were associated with less cardiac protection and more pro
      inflammatory states than normal subjects or IHD patients with either normal or
      high serum iron.

PMID- 16793034
TI  - Cryopreservation of isolated human hepatocytes for transplantation: State of the
      art.
AB  - Hepatocytes isolated from unused donor livers are being used for transplantation
      in patients with acute liver failure and liver-based metabolic defects. As large
      numbers of hepatocytes can be prepared from a single liver and hepatocytes need
      to be available for emergency and repeated treatment of patients it is essential
      to be able to cryopreserve and store cells with good thawed cell function. This
      review considers the current status of cryopreservation of human hepatocytes
      discussing the different stages involved in the process. These include pre
      treatment of cells, freezing solution, cryoprotectants and freezing and thawing
      protocols. There are detrimental effects of cryopreservation on hepatocyte
      structure and metabolic function, including cell attachment, which is important
      to the engraftment of transplanted cells in the liver. Cryopreserved human
      hepatocytes have been successfully used in clinical transplantation, with
      evidence of replacement of missing function. Further optimisation of hepatocyte
      cryopreservation protocols is important for their use in hepatocyte
      transplantation.

PMID- 16793035
TI  - The transcription factors Emx1 and Emx2 suppress choroid plexus development and
      promote neuroepithelial cell fate.
AB  - The transcription factors Emx1 and Emx2 exert important functions during
      development of the cerebral cortex, including its arealization. Here, we
      addressed their role in development of the derivatives of the midline region in
      the telencephalon. The center of the midline region differentiates into the
      choroid plexus, but little is known about its molecular specification. As we
      noted a lack of Emx1 or 2 expression in the midline region early in development,
      we interfered by misexpressing Emx1 and/or Emx2 in this region of the chick
      telencephalon. Ectopic expression of either Emx1 or Emx2 prior to HH 13
      instructed a neuroepithelial identity in the previous midline region instead of a
      choroidal fate. Thus, Gli3 and Lhx2 normally restricted to the neuroepithelium
      expanded into the Emx misexpressing region. This was accompanied by down
      regulation of Otx2 and BMP7, which implicates that these factors are essential
      for choroid plexus specification and differentiation. Interestingly, the region
      next to the ectopic Emx-misexpression then acquired a hybrid identity with some
      choroidal features such as Bmp7, Otx2 and Ttr gene expression, as well as some
      neuroepithelial features. These observations indicate that the expression levels
      of Emx1 and/or Emx2 restrict the prospective choroid plexus territory, a novel
      role of these transcription factors.

PMID- 16793036
TI  - Beta-glucan ameliorates methotrexate-induced oxidative organ injury via its
      antioxidant and immunomodulatory effects.
AB  - Methotrexate is an antifolate that is widely used in the treatment of rheumatic
      disorders and malignant tumors. The efficacy of methotrexate is often limited by
      severe side effects and toxic sequelae, where oxidative stress is noticeable. In
      the present study, the possible protective effect of beta-glucan in methotrexate
      induced toxicity was investigated. Following a single dose of methotrexate
      injection (20 mg/kg), either saline or beta-glucan (50 mg/kg; orally) was
      administered for 5 days. After decapitation of the rats, trunk blood was obtained
      and the ileum, liver and kidney were removed to measure tissue malondialdehyde
      (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen
      content, as well as histological examination. Methotrexate caused a significant
      decrease in GSH levels, while MDA levels, MPO activity and collagen content were
      increased in all the tissues (P<0.05-0.001). On the other hand, administration of
      beta-glucan following methotrexate abolished the depletion of GSH and inhibited
      the increases in MDA, MPO activity and collagen content, while the histological
      analysis revealed that beta-glucan attenuated the tissue damage. Stimulation
      index, an indicator of oxidative burst in the neutrophils, was decreased by
      methotrexate (P<0.001), while beta-glucan abolished this effect. Furthermore,
      increased leukocyte apoptosis and cell death in methotrexate-treated animals were
      inhibited by beta-glucan (P<0.05). Thus, the findings of the present study
      suggest that beta-glucan, through its antioxidant and immunoregulatory effects,
      may be of therapeutic value in alleviating the leukocyte apoptosis, oxidative
      tissue injury and thereby the intestinal and hepatorenal side effects of
      methotrexate treatment.

PMID- 16793037
TI  - Myostatin regulation of muscle development: molecular basis, natural mutations,
      physiopathological aspects.
AB  - Since its identification in 1997, myostatin has been considered as a novel and
      unique negative regulator of muscle growth, as mstn-/- mice display a dramatic
      and widespread increase in skeletal muscle mass. Myostatin also appears to be
      involved in muscle homeostasis in adults as its expression is regulated during
      muscle atrophy. Moreover, deletion of the myostatin gene seems to affect adipose
      tissue mass in addition to skeletal muscle mass. Natural myostatin gene mutations
      occur in cattle breeds such as Belgian Blue, exhibiting an obviously increased
      muscle mass, but also in humans, as has recently been demonstrated. Here we
      review these natural mutations and their associated phenotypes as well as the
      physiological influence of the alterations in myostatin expression and the
      physiopathological consequences of changes in myostatin expression, especially
      with regard to satellite cells. Interestingly, studies have demonstrated some
      rescue effects of myostatin in muscular pathologies such as myopathies, providing
      a novel pharmacological strategy for treatment. Furthermore, the myostatin
      pathway is now better understood thanks to in vitro studies and it consists of
      inhibition of myoblast progression in the cell cycle, inhibition of myoblast
      terminal differentiation, in both cases associated to protection from apoptosis.
      The molecular pathway driving the myogenic myostatin influence is currently under
      extensive study and many molecular partners of myostatin have been identified,
      suggesting novel potent muscle growth enhancers for both human and agricultural
      applications.

PMID- 16793038
TI  - Development of the human retina in the absence of ganglion cells.
AB  - Retinal development was studied in eyes from fetal and neonatal human
      anencephalic (AnC) and normal age-matched infants to determine the time of
      retinal ganglion cell (GC) loss and its effect on the development of other
      retinal neurons. At fetal week (Fwk) 14, GC loss was evident in central retina
      and by Fwk 19-20 almost all GC were absent, although immunocytochemical labeling
      for GC markers brain 3, neurofilament M and parvalbumin detected a few GC in the
      AnC far periphery at older ages. The inner nuclear and inner plexiform (IPL)
      layers showed variable amounts of thinning but all normal bipolar (BP) and
      horizontal cell markers were still present. The amacrine (AM) labels calbindin
      and calretinin were markedly reduced. Lamination for these markers in the IPL was
      less organized than in normal retinas, with BP and AM markers extending into the
      degenerated GC layer. Cone and rod photoreceptors had normal morphology and
      topography in AnC retina and each expressed normal phototransduction and synaptic
      markers. The prospective fovea was identified in AnC neonatal retina by cone
      packing and the absence of immunolabeled rod photoreceptors. In one AnC neonatal
      retina, blood vessels and astrocytes extended across the inner retina in the
      putative fovea and there was no evidence of a pit. In another AnC neonatal
      retina, blood vessels and astrocytes formed a foveal avascular zone in the inner
      retina and a shallow pit was present within this zone. However, both foveas
      showed evidence for the onset of cone elongation and packing. These findings
      support the model of Springer and Hendrickson [2005; Vis. Neurosci. 22, 171] in
      which the foveal avascular zone is critical for pit formation, but suggest that
      mechanisms inherent to the outer retina may be involved in early stages of foveal
      cone packing.

PMID- 16793039
TI  - Improved transduction of human corneal epithelial progenitor cells with cell
      targeting adenoviral vectors.
AB  - The development of vectors and techniques to transfer therapeutic genes to
      corneal epithelium has broad clinical applications. To determine if adenoviral
      (Ad5) vectors could be tailored to increase transduction of corneal epithelial
      progenitor cells expressing epidermal growth factor receptor (EGFR), the
      feasibility of targeting gene therapy vectors to genetically modify primary
      cultured human corneal epithelial cells (PHCEC) was evaluated. PHCECs were
      cultured from human limbal explants and transduced with Ad5 vectors containing
      the enhanced green fluorescent protein (GFP) reporter cassette to mediate gene
      transfer. The efficiencies of transduction with different Ad5 dosages and
      different time periods of exposure were compared. Metabolically biotinylated Ad5
      vectors were retargeted to PHCECs using biotinylated epidermal growth factor
      (EGF) as a cell-targeting ligand. Phenotypes and function assays of transduced
      cells were determined by real-time PCR and BrdU incorporation. Ad5 vectors
      transduced approximately 50-93% of PHCEC at 10-100 PFU/cell in a dose-dependent
      manner and the transgene persisted for more than 2 weeks in vitro. Retargeting of
      biotinylated Ad5 with EGF increased transduction of EGFR and ABCG2-expressing
      corneal epithelial progenitor cells up to nine-fold and reduced transduction of
      K12 and involucrin-expressing differentiated corneal epithelial cells and had
      higher BrdU incorporation indexes. These data provide proof of principle that
      ligand-bearing modified Ad5 vectors can target a population of corneal epithelial
      progenitor cells for corneal gene therapy.

PMID- 16793040
TI  - Degeneration and proliferation of astrocytes in the mouse dentate gyrus after
      pilocarpine-induced status epilepticus.
AB  - Astrocytes are relatively resistant to injury compared to neurons and
      oligodendrocytes. Here, we report transient region-specific loss of astrocytes in
      mice early after pilocarpine-induced status epilepticus (SE). In the dentate
      hilus, immunoreactivity for glial acidic fibrillary protein (GFAP) was decreased,
      and the number of healthy appearing GFAP- or S100beta-positive cells was
      significantly reduced (> or =65%) 1 and 3 days after pilocarpine-induced SE. Many
      remaining GFAP-positive cells were shrunken, and 1 day after SE electron
      microscopy revealed numerous electron-dense degenerating astrocyte processes and
      degenerating glial somata in the hilus. Degeneration of GFAP-expressing cells may
      be linked to hilar neuronal death, because we did not observe loss of astrocytes
      after kainate-induced SE, after which hilar neurons remained intact. Ten days
      after SE, hilar GFAP immunoreactivity had returned, partially from GFAP-positive
      cells in the hilus. Unlike control mice, many GFAP-positive hilar processes
      originated from cell bodies located in the subgranular zone (SGZ). To investigate
      whether proliferation contributes to hilar repopulation, we injected 5-bromo-2'
      deoxyuridine (BrdU) 3 days after SE. Five hours later and up to 31 days after SE,
      many BrdU/GFAP colabeled cells were found in the hilus and the SGZ, some with
      hilar processes, indicating that proliferation in both areas contributes to
      generation of hilar astrocytes and astrocyte processes. In contrast to
      pilocarpine-induced SE in mice, astrocyte degeneration was not found after
      pilocarpine-induced SE in rats. These findings demonstrate astrocyte degeneration
      in the mouse dentate hilus specifically in the mouse pilocarpine epilepsy model,
      followed by astrogenesis leading to hilar repopulation.

PMID- 16793041
TI  - First meiosis errors in immature oocytes generated by stimulated cycles.
AB  - OBJECTIVE: To investigate chromosomal errors detected by first polar body (PB)
      biopsy in relation to the nuclear maturity of the oocytes. DESIGN: Retrospective
      study. SETTING: Reproductive medicine unit. PATIENT(S): Eighty-seven cycles were
      examined by PB biopsy for aneuploidy. Indications were maternal age >or=38 years
      (49 cycles), repeated IVF failures (22 cycles), and others (16 cycles).
      INTERVENTION(S): First polar bodies were analyzed for the chromosomes 13, 16, 18,
      21, and 22 in both in vivo and in vitro matured oocytes. Euploid oocytes were
      inseminated by intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S):
      Chromosomal status of the analyzed oocytes, development after intracytoplasmic
      sperm injection, pregnancy, and implantation rates. RESULT(S): In in vitro
      matured oocytes, the proportion of chromosomal abnormalities was higher than in
      in vivo matured oocytes (70% vs. 54%, P<.005), with complex abnormalities being
      the prevailing defect (62% vs. 40%, P<.001). Conversely, the presence of an extra
      chromatid or the lack of a chromatid was more frequent in in vivo than in in
      vitro matured oocytes (55% vs. 34%, P<.001). CONCLUSION(S): The low viability of
      in vitro matured oocytes from stimulated cycles could be related to a
      significantly higher proportion of chromosomal abnormalities compared with in
      vivo matured oocytes. Complex abnormalities, involving two or more chromosomes,
      gave the strongest contribution to the detected increase.

PMID- 16793042
TI  - Serotonergic modulation of male-like pseudocopulatory behavior in the
      parthenogenetic whiptail lizard, Cnemidophorus uniparens.
AB  - Hormone-neurotransmitter interactions form an important link through which
      hormones influence a variety of behavioral processes. Typically, sexual behavior
      is dimorphic with males mounting receptive females. In the all-female lizard
      species Cnemidophorus uniparens, individuals display both male-like
      pseudocopulation and female-like receptivity. These respective behavioral states
      are correlated with high circulating concentrations of progesterone following
      ovulation and of estrogen preceding it. In sexual species, serotonin is involved
      in male-typical mounting, and, as reported here, in male-like pseudosexual
      behavior in this unisexual species. In the first study, C. uniparens were
      ovariectomized and treated systemically with exogenous androgen, a hormonal
      regimen that results in individuals displaying only male-like pseudosexual
      behavior. An increase in serotonin levels in the preoptic area coupled with the
      suppression of male-like pseudocopulation was observed in androgen-treated
      lizards injected with 5-hydroxytryptophan (the precursor of serotonin) and
      clorgyline (a monoamine oxidase inhibitor) compared to vehicle-treated controls.
      Our second experiment involved ovariectomizing lizards and either injecting them
      with estradiol or implanting them with either an empty (Blank) or a progesterone-
      or testosterone-containing Silastic capsule. Treatment with para
      chlorophenylalanine (an inhibitor of tryptophan hydroxylase) facilitated male
      like pseudosexual behavior depending on the circulating hormonal milieu and
      decreased serotonin levels in the preoptic area. Our data suggest that serotonin
      is inhibitory to male-like pseudosexual behavior in C. uniparens but more
      importantly that the hormonal environment modulates the serotonin system at the
      level of the preoptic area, with the serotonergic system then establishing
      behavioral thresholds that allow for this behavior to be "gated".

PMID- 16793043
TI  - Career choices in health care: is nursing a special case? A content analysis of
      survey data.
AB  - BACKGROUND: As demand for nurses and other health professionals continues to
      outstrip supply it is important to understand what motivates individuals to join
      a non-medical health profession. OBJECTIVES: The objectives of this study were to
      investigate students' reasons for choosing a particular nursing specialism,
      midwifery or other non-medical health profession, and to compare motivation
      factors across professions, gender, age, level of award, prior qualifications,
      prior experience and over time. DESIGN: A prospective follow-up study collected
      survey responses at the beginning and end of pre-qualifying professional
      programmes. SETTING: The study took place in one large United Kingdom faculty.
      PARTICIPANTS: The study participants were 775 first-year students undertaking non
      medical health professional programmes and 393 qualifying students. METHODS: An
      open-ended question was included in a self-completed questionnaire administered
      at entry and at qualification. Content analysis identified themes. RESULTS:
      Altruism was the most frequently cited reason for wishing to join a non-medical
      health profession, followed by personal interest/abilities, professional
      values/rewards, and prior experience of the area. Students entering nursing were
      less likely to cite an altruistic motivation than those entering other non
      medical health professions (chi(2)=21.61, df=1, p<0.001). On entry, adult
      nursing, children's nursing and radiotherapy students were least likely to cite
      professional values/rewards (chi(2)=20.38, df=8, p=0.009). Students on degree
      level programmes were more likely to report altruism than those on diploma level
      courses (chi(2)=17.37, df=1, p<0.001). Differences were also identified between
      the two data collection points. The number of students identifying altruism
      (chi(2)=3.97, p=0.046) and professional values/rewards (chi(2)=6.67, p=0.010)
      decreased over time. CONCLUSION: Findings suggest that although a service
      orientation remains a key factor in choosing nursing, students also look for a
      career which matches their interests and attributes, as well as offering
      professional values and rewards. Nursing may be in danger of losing service
      orientated recruits to other non-medical health professions.

PMID- 16793044
TI  - Protecting the self: a descriptive qualitative exploration of how registered
      nurses cope with working in surgical areas.
AB  - AIMS: This paper aims to explore and describe how qualified nurses working with
      in, in-patient surgical areas cope with the daily experiences they are exposed
      to. BACKGROUND: It has long been recognised that many aspects of nursing work can
      result in high levels of stress, with negative consequences for the individual
      nurse and patient care. Difficulties in coping with nursing work can also result
      in burnout, as well as raising concerns about cognitive dissonance, emotional
      labour and the use of emotional barriers. Why some nurses are more prone to
      experience these phenomena than others, is unclear. METHOD: A descriptive
      qualitative approach is taken using a purposive, theoretically congruent sample
      of 16 qualified registered nurses all of whom participated in a semi-structured
      interview during 2002. All interviews were tape recorded and transcribed verbatim
      and then analysed using the four stages outlined by Morse and Field [Morse, J.M.,
      Field, P.A., 1996. Nursing Research: The Application of Qualitative Approaches.
      Chapman & Hall, London]. FINDINGS: Three key themes emerged from analysis;
      relationships with patients, being a person and the effect of experience. All
      three interlink to describe a process whereby the individual switches off from
      the environment around them by adopting a working persona which is different but
      related to their own personal persona and is beneficially enhanced as a
      consequence of experience. CONCLUSION: Working as a nurse results in exposure to
      potentially distressing and stressful events from which it is important to
      protect the self. Participants in this study achieve protection by the
      development of a working persona which facilitates switching off and is
      beneficially enhanced by experience.

PMID- 16793045
TI  - Characterisation of EmMPK1, an ERK-like MAP kinase from Echinococcus
      multilocularis which is activated in response to human epidermal growth factor.
AB  - Mitogen-activated protein (MAP) kinases are key regulators of cellular signalling
      systems that mediate responses to a wide variety of extracellular stimuli and
      should also play a central role in developmental mechanisms of parasitic
      helminths. Until now, however, no MAP kinase orthologue has been characterised in
      a member of this parasite group. Here, we report the identification and
      characterisation of such a molecule, EmMPK1, from the human parasitic cestode
      Echinococcus multilocularis. Using a degenerative PCR approach, we isolated and
      completely sequenced the 1.2kb cDNA for EmMPK1 which displays significant
      homologies to known MAP kinases of different phylogenetic origin. EmMPK1 contains
      all amino acid residues which are characteristic for MAP kinases, including a
      conserved TEY motif which identifies the protein as a member of the ERK subfamily
      of MAP kinases. The corresponding gene, emmpk1 (6.9 kb), was characterised and
      contained 10 introns. Southern blot hybridisation studies showed that emmpk1 is
      present as single copy locus in E. multilocularis. Using RT-PCR analyses we
      demonstrated that emmpk1 is expressed in form of three different transcripts
      which derive from alternative splice acceptor site utilisation at intron 9. Using
      EmMPK1-specific antibodies in Western blot studies and immunohistochemistry, we
      detected the Echinococcus protein and its phosphorylated form in the larval
      stages metacestode and protoscolex during in vitro cultivation and during an
      infection of the intermediate host. EmMPK1, immunoprecipitated from Echinococcus
      lysate, was able to phosphorylate myelin basic protein in activity assays,
      indicating that it is a functionally active MAP kinase. Finally, we also show
      that phosphorylation of EmMPK1 is specifically induced in vitro-cultivated E.
      multilocularis metacestode vesicles in response to exogenous host serum and upon
      addition of human epidermal growth factor. These data indicate that the E.
      multilocularis metacestode is able to sense epidermal growth factor from the host
      which results in an activation of the parasite's MAP kinase cascade.

PMID- 16793046
TI  - Expression of IL-4 receptor on non-bone marrow-derived cells is necessary for the
      timely elimination of Strongyloides venezuelensis in mice, but not for intestinal
      IL-4 production.
AB  - In rodents and in humans, Strongyloides infection induces an immune response
      which is predominantly Th2 in nature. In an attempt to understand the role of the
      IL-4R/STAT6 signaling pathway, the pathway activated by the Th2 cytokines IL-4
      and IL-13, in the induction of protection during Strongyloides venezuelensis
      infection, we have carried out experiments in mice lacking the IL-4Ralpha chain.
      Experiments were also carried out in STAT6 (STAT6(-/-)) and IL-12-deficient (IL
      12(-/-)) mice for comparison. There was enhancement of IL-13 and abolition of IFN
      gamma production in the small intestine of 7 day-infected IL-12(-/-) animals but
      worm elimination proceeded with very similar kinetics to those of wild-type mice.
      In IL-4Ralpha- or STAT6-deficient mice, there was a delay in parasite elimination
      and a large number of S. venezuelensis adult worms was still present in the small
      intestine 14 days after infection. Moreover, IgE production was completely
      abolished in IL-4Ralpha- or STAT6-deficient mice but tissue eosinophilia was
      normally induced by the parasite infection in deficient mice. Bone marrow
      transfer experiments showed that worm elimination occurred when a functional IL-4
      receptor was present only in non-bone marrow-derived cells but not when IL-4R was
      only expressed in bone marrow cells. The induction of IL-4, but not IL-13,
      occurred independently of IL-4R. We believe these results are the first direct
      evidence that the mechanism responsible for the timely elimination of S.
      venezuelensis is dependent on the activation of IL-4R and STAT6. Moreover, a
      functional protective response is dependent on the expression of IL-4Ralpha on
      non-bone marrow-derived cells.

PMID- 16793047
TI  - Age-dependent association between hepatic lipase gene C-480T polymorphism and the
      risk of pre-hospital sudden cardiac death: the Helsinki Sudden Death Study.
AB  - OBJECTIVE: We investigated the association between hepatic lipase (HL) C-480T
      polymorphism and the risk of acute myocardial infarction (AMI) as well as pre
      hospital sudden cardiac death (SCD). METHODS: Seven hundred sudden or unnatural
      pre-hospital deaths of middle-aged (33-70 years, mean 53 years) Caucasian Finnish
      men were subjected to detailed autopsy (Helsinki Sudden Death Study). Genotype
      data were obtained for 682 men. RESULTS: In logistic regression analysis with
      age, body mass index, hypertension, diabetes, smoking and alcohol consumption as
      covariates, men with the TT genotype had an increased risk for SCD and AMI
      compared to CC carriers (OR=3.0, P=0.011; and OR=3.7, P=0.003). There was a
      significant age-by-genotype interaction (P<0.05) on the risk of SCD. Compared to
      CC genotype carriers, the association between the TT genotype and SCD was
      particularly strong (P=0.001) among men <53 years of age, but this association
      was non-significant among older men. This was mainly due to a strong association
      between the TT genotype and AMI due to severe coronary disease in the absence of
      thrombosis. Carriers of the TT genotype were more likely to have severe coronary
      stenoses (> or =50%) than men with the CT or CC genotype (P=0.019). CONCLUSIONS:
      The results suggest that HL C-480T polymorphism is a strong age-dependent risk
      factor of SCD in early middle-aged men.

PMID- 16793048
TI  - Aspirin is a substrate for paraoxonase-like activity: implications in
      atherosclerosis.
AB  - Paraoxonase 1 (PON 1) is an enzyme that is promiscuous in its ability to
      hydrolyze various types of substrates. It hydrolyzes aryl esters, phosphate
      esters, lactones, and reduces lipid peroxides to hydroxides. Aspirin is an aryl
      ester with a short plasma half life. We hypothesized that aspirin would be
      effectively hydrolyzed by PON 1 and many of its anti-atherogenic effects, at
      least in part, could be accounted for by its antioxidant product, salicylic acid.
      In this study, we determined the ability of human plasma and PON 1-rich HDL to
      hydrolyze acetyl ester of salicylic acid (aspirin). The ability of aspirin to
      compete for the hydrolysis of paraoxon and p-nitrophenylacetate was determined.
      In addition, nitrated aspirin was synthesized and tested directly for hydrolysis.
      Aspirin competed for the hydrolysis of paraoxon and p-nitrophenylacetate by HDL
      in a dose-dependent manner. Human plasma and HDL were also able to hydrolyze
      nitroaspirin and aspirin and release nitrosalicylic acid and salicylic acid,
      respectively. These findings suggest that salicylic acid might be generated in
      the plasma from aspirin. The ability of long-term treatment with aspirin to
      retard atherosclerosis might be dependent on the generation of free salicylic
      acid, a scavenger of free radicals.

PMID- 16793049
TI  - RETRACTED: Postprandial lipemia and LDL conjugated dienes predict serum GGT and
      liver histology in NASH.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see . The Publisher apologizes for any inconvenience this may
      cause.

PMID- 16793050
TI  - Nanomechanical properties of individual chondrocytes and their developing growth
      factor-stimulated pericellular matrix.
AB  - The nanomechanical properties of individual cartilage cells (chondrocytes) and
      their aggrecan and collagen-rich pericellular matrix (PCM) were measured via
      atomic force microscope nanoindentation using probe tips of two length scales
      (nanosized and micron-sized). The properties of cells freshly isolated from
      cartilage tissue (devoid of PCM) were compared to cells that were cultured for
      selected times (up to 28 days) in 3-D alginate gels which enabled PCM assembly
      and accumulation. Cells were immobilized and kept viable in pyramidal wells
      microfabricated into an array on silicon chips. Hertzian contact mechanics and
      finite element analyses were employed to estimate apparent moduli from the force
      versus depth curves. The effects of culture conditions on the resulting PCM
      properties were studied by comparing 10% fetal bovine serum to medium containing
      a combination of insulin growth factor-1 (IGF-1)+osteogenic protein-1 (OP-1).
      While both systems showed increases in stiffness with time in culture between
      days 7 and 28, the IGF-1+OP-1 combination resulted in a higher stiffness for the
      cell-PCM composite by day 28 and a higher apparent modulus of the PCM which is
      compared to the FBS cultured cells. These studies give insight into the temporal
      evolution of the nanomechanical properties of the pericellar matrix relevant to
      the biomechanics and mechanobiology of tissue-engineered constructs for cartilage
      repair.

PMID- 16793051
TI  - Preparation and characterization of surfactant-free polystyrene/layered double
      hydroxide exfoliated nanocomposite via soap-free emulsion polymerization.
AB  - The soap-free emulsion polymerization has been applied for preparing the
      surfactant-free polystyrene/layered double hydroxide exfoliated nanocomposite.
      The XRD and TEM determinations have been used to monitor the changes of
      interlayer spacing and morphology during polymerization. The results show that
      the obtained nanocomposite has the homogeneous structure of polymeric and
      inorganic components. Due to the absence of organic surfactant, the PS/LDH
      nanocomposite shows a remarked improvement on the onset decomposition temperature
      compared with virgin PS.

PMID- 16793052
TI  - Adsorption of ethoxylated cationic surfactants on self-assembled monolayers of
      alkanethiols on gold using surface plasmon resonance detection.
AB  - Adsorption of a series of ethoxylated cationic surfactants at model surfaces of
      alkanethiol self-assembled monolayers was studied by the surface plasmon
      resonance technique. Model surfaces were tailor-made by choosing alkanethiols or
      mixtures of alkanethiols with methyl, hydroxyl, carboxyl, and trimethylammonium
      groups in terminal position. The ethoxylated and quaternized cationic surfactants
      having from 2 to 18 oxyethylene units, showed a decrease in adsorbed amount with
      increasing oxyethylene chain length for both hydrophobic and hydrophilic
      surfaces. On a negatively charged surface, containing carboxylate groups, the
      surfactant with only two oxyethylene groups adsorbed strongly due to
      electrostatic attraction and the adsorption increased with increasing amount of
      surface carboxylate groups. This work shows the usefulness of self-assembled
      alkanethiols on gold as a tool for performing surfactant adsorption studies on
      surfaces with variable hydrophobicity and charge.

PMID- 16793053
TI  - A thermodynamic study of GPI-anchored and soluble form of alkaline phosphatase
      films at the air-water interface.
AB  - Glycosylphosphatidyl inositol (GPI) anchored proteins are localized and clustered
      on the outer layer of the plasma membranes forming microdomains. Among them,
      mammalian alkaline phosphatases (AP-GPI) are widely distributed enzymes. They can
      also exist as soluble proteins without anchor (APs). Using the Langmuir film
      technique, we study the thermodynamic properties of monolayers for both protein
      forms at the air-buffer interface. The enzymatic activity is maintained at the
      interface but the adsorption of the two forms of AP is very different. AP-GPI
      presents a higher surface activity and a larger molecular area than the soluble
      form. The molecular area deduced for high surface pressures suggests a different
      organization of the monolayers for these two forms. APs molecules seem to adsorb
      as a multilayer at the interface while AP-GPI appear to be orientated with the
      major axis parallel to the interface. This orientation allows the accessibility
      of AP-GPI enzymatic sites that are turned in direction of the subphase as in vivo
      where the active sites must be turned outside of the membrane.

PMID- 16793054
TI  - Gushing in canned beer: the effect of ultrasonic vibration.
AB  - Everybody has had the experience of a canned carbonated drink overflowing and
      soiling their clothes. It is difficult to guess the amount of overflow before
      opening the can, although the phenomenon can be simply explained as the result of
      the formation of gas bubbles. In this article, we report the surprising result
      that intensive shaking using ultrasonic vibration can calm this effect in beer.
      These experiments showed evidence of a memory effect in liquid. The 'calming
      down' is due to a fine balancing act between a change in the amount of
      microbubbles (or embryos) and a change in the pattern of their size distribution.
      Our experimental evidence shows that modification of the pre-existing
      microbubbles noticeably influences the subsequent nucleation, and this may open a
      new route to nucleation studies.

PMID- 16793055
TI  - Multidimensional shape similarity in the development of visual object
      classification.
AB  - The current work examined age differences in the classification of novel object
      images that vary in continuous dimensions of structural shape. The structural
      dimensions employed are two that share a privileged status in the visual analysis
      and representation of objects: the shape of discrete prominent parts and the
      attachment positions of those parts. Experiment 1 involved a triad classification
      task in which participants at each of three different ages (5 years, 8 years, and
      adult) classified object images from two distinct stimulus sets. Across both
      sets, the youngest children demonstrated a systematic bias toward the shape of
      discrete parts during their judgments. With increasing age, participants
      increasingly came to select both the shape and the position of parts when
      classifying the images. The findings from Experiment 2 indicate that the local
      shape bias observed in young children's classifications is not merely a
      consequence of a discrimination advantage for that dimension. Results are
      discussed in relation to corresponding age-related changes in other functional
      contexts of visual processing.

PMID- 16793056
TI  - A comparison of Chryseobacterium indologenes pathogenicity to the soft tick
      Ornithodoros moubata and hard tick Ixodes ricinus.
AB  - A yellow-pigmented Gram-negative bacterium, Chryseobacterium indologenes, was
      found in the gut contents of about 65% of soft ticks Ornithodoros moubata from a
      perishing laboratory colony. The isolated putative pathogen, C. indologenes, was
      susceptible to cotrimoxazol and addition of this antibiotic (Biseptol 480) to the
      blood meal significantly decreased the tick mortality rate. The artificial
      infection of healthy O. moubata by membrane feeding on blood contaminated with C.
      indologenes was lethal to all ticks at concentrations 10(6) bacteria/ml. On the
      contrary, a similar infection dose applied to the hard tick Ixodes ricinus by
      capillary feeding did not cause significant mortality. Examination of guts
      dissected from infected O. moubata and I. ricinus revealed that C. indologenes
      was exponentially multiplied in the soft tick but were completely cleared from
      the gut of the hard ticks within 1 day. In both tick species, C. indologenes were
      found to penetrate from the gut into the hemocoel. The phagocytic activity of
      hemocytes from both tick species was tested by intrahaemocoelic microinjection of
      C. indologenes and evaluated by indirect fluorescent microscopy using antibodies
      raised against whole bacteria. Hemocytes from both tick species displayed
      significant phagocytic activity against C. indologenes. All O. moubata injected
      with C. indologenes died within 3 days, whereas the increase of the mortality
      rate of I. ricinus was insignificant. Our results indicate that hard ticks
      possess much more efficient defense system against infection with C. indologenes
      than the soft ticks. Thus, C. indologenes infection has the potential to be a
      relevant comparative model for the study of tick immune reactions to transmitted
      pathogens.

PMID- 16793057
TI  - Morphometry of the midgut epithelium of Diatraea saccharalis Fabricius, 1794
      (Lepidoptera) parasitized by Cotesia flavipes Cameron, 1891 (Hymenoptera).
AB  - The morphometric study of the midgut in Diatraea saccharalis (Lepidoptera) larvae
      parasitized by the Cotesia flavipes (Hymenoptera) showed that there was
      significant increase in the columnar, goblet and regenerative cells and their
      nuclei; the midgut lumen diameter and the epithelial height were also increased
      in the parasitized larvae. The multivariate analysis showed that parasitism
      affected the columnar cell only in the posterior region, and the goblet cells
      along the midgut length (anterior and posterior regions).

PMID- 16793058
TI  - Horizontal and vertical transmission of viruses in the honey bee, Apis mellifera.
AB  - The most crucial stage in the dynamics of virus infections is the mode of virus
      transmission. In general, transmission of viruses can occur through two pathways:
      horizontal and vertical transmission. In horizontal transmission, viruses are
      transmitted among individuals of the same generation, while vertical transmission
      occurs from mothers to their offspring. Because of its highly organized social
      structure and crowded population density, the honey bee colony represents a risky
      environment for the spread of disease infection. Like other plant and animal
      viruses, bee viruses use different survival strategies, including utilization of
      both horizontal and vertical routes, to transmit and maintain levels in a host
      population. In this review, we explore the current knowledge about the honey bee
      viruses and transmission routes of bee viruses. In addition, different
      transmission strategies on the persistence and dynamics of host-pathogen
      interactions are also discussed.

PMID- 16793059
TI  - Preconditioning by angiotensin II: a tale of more than two kinases.

PMID- 16793060
TI  - Dysfunction of cardiac ryanodine receptors in the metabolic syndrome.
AB  - This study examined the hypothesis that the prediabetic metabolic syndrome alters
      expression, phosphorylation state and binding affinity of cardiac RyR2. Real-time
      PCR and Western blot analysis were used to assess mRNA and protein expression in
      the left ventricle, right ventricle and right atrium from control (n=5) and
      chronically high-fat-fed (n=5) dogs with the metabolic syndrome. Functional
      integrity of RyR2 was assessed by RyR2-Ser2809 phosphorylation and the receptor's
      ability to bind [3H]ryanodine. We found that RyR2 phosphorylation at Ser2809 was
      significantly elevated in right and left ventricle from high-fat-fed dogs
      compared to normal control dogs. This hyperphosphorylation was associated with a
      decrease in RyR2 binding affinity in right and left ventricle (high-fat diet=80.2
      and 90.5 fmol/mg protein vs. control=243.6 and 200.9 fmol/mg protein,
      respectively) and a decrease in cardiac index in exercising dogs. RyR2
      phosphorylation at Ser2809 and RyR2 binding affinity were not altered in the
      right atria of high-fat-fed dogs. In addition, no significant differences in
      cardiac RyR2 mRNA or protein expression were noted between groups. These data
      suggest that alterations in RyR2 could be an important mechanism of early cardiac
      dysfunction in obesity and insulin resistance.

PMID- 16793061
TI  - Crystal structure of 3-chlorocatechol 1,2-dioxygenase key enzyme of a new
      modified ortho-pathway from the Gram-positive Rhodococcus opacus 1CP grown on 2
      chlorophenol.
AB  - The crystal structure of the 3-chlorocatechol 1,2-dioxygenase from the Gram
      positive bacterium Rhodococcus opacus (erythropolis) 1CP, a Fe(III) ion
      containing enzyme specialized in the aerobic biodegradation of 3-chloro- and
      methyl-substituted catechols, has been solved by molecular replacement techniques
      using the coordinates of 4-chlorocatechol 1,2-dioxygenase from the same organism
      (PDB code 1S9A) as a starting model and refined at 1.9 A resolution (R(free)
      21.9%; R-factor 17.4%). The analysis of the structure and of the kinetic
      parameters for a series of different substrates, and the comparison with the
      corresponding data for the 4-chlorocatechol 1,2-dioxygenase isolated from the
      same bacterial strain, provides evidence of which active site residues are
      responsible for the observed differences in substrate specificity. Among the
      amino acid residues expected to interact with substrates, only three are altered
      Val53(Ala53), Tyr78(Phe78) and Ala221(Cys224) (3-chlorocatechol 1,2-dioxygenase(4
      chlorocatechol 1,2-dioxygenase)), clearly identifying the substitutions
      influencing substrate selectivity in these enzymes. The crystallographic
      asymmetric unit contains eight subunits (corresponding to four dimers) that show
      heterogeneity in the conformation of a co-crystallized molecule bound to the
      catalytic non-heme iron(III) ion resembling a benzohydroxamate moiety, probably a
      result of the breakdown of recently discovered siderophores synthesized by Gram
      positive bacteria. Several different modes of binding benzohydroxamate into the
      active site induce distinct conformations of the interacting protein ligands
      Tyr167 and Arg188, illustrating the plasticity of the active site origin of the
      more promiscuous substrate preferences of the present enzyme.

PMID- 16793062
TI  - Identification and characterization of the chromatin-binding domains of the HIV-1
      integrase interactor LEDGF/p75.
AB  - Depletion of the transcriptional co-activator LEDGF/p75 by RNA interference
      alters the genome-wide pattern of HIV-1 integration, reducing integration into
      active genes, reducing integration into LEDGF/p75-regulated genes, and increasing
      integration into G+C-rich sequences. LEDGF/p75 is also able to act as a molecular
      tether linking HIV-1 integrase protein to chromatin, a phenomenon likely to
      underlie the integration site distribution effects. The LEDGF/p75 integrase
      binding domain has been established but the domain or domains responsible for the
      chromatin-binding component of tethering are unknown. Here, we identify and
      characterize these domains. Complementary methods were used to assess condensed
      and uncondensed chromatin, and to determine the stringency of chromatin binding.
      Immuno-localization analyses revealed that an N-terminal PWWP domain and its beta
      barrel substructure are needed for binding to metaphase chromatin. However, the
      PWWP domain is insufficient to transfer metaphase chromatin binding to green
      fluorescent protein, which requires addition of a downstream charged region
      (CR1). Biochemical analysis showed that full-length LEDGF/p75 resists Triton X
      100 extraction from chromatin. To transfer Triton-resistant chromatin binding to
      green fluorescent protein, PWWP-CR1 is necessary but not sufficient. Further
      inclusion of a tandem pair of AT-hooks in combination with at least one of two
      identified downstream charged regions (CR2 or CR3) is needed. Deletion of just
      the PWWP or the AT-hook domain from full-length LEDGF/p75 reduced Triton
      resistant chromatin binding, while deletion of both elements abolished it,
      underscoring their dominant and cooperative role. The results establish a
      molecular mechanism for LEDGF/p75-mediated tethering of HIV-1 integrase to
      chromatin.

PMID- 16793063
TI  - The structure of the RNA m5C methyltransferase YebU from Escherichia coli reveals
      a C-terminal RNA-recruiting PUA domain.
AB  - Nucleotide methylations are the most common type of rRNA modification in
      bacteria, and are introduced post-transcriptionally by a wide variety of site
      specific enzymes. Three 5-methylcytidine (m(5)C) bases are found in the rRNAs of
      Escherichia coli and one of these, at nucleotide 1407 in 16 S rRNA, is the
      modification product of the methyltransferase (MTase) YebU (also called RsmF).
      YebU requires S-adenosyl-l-methionine (SAM) and methylates C1407 within assembled
      30 S subunits, but not in naked 16 S rRNA or within tight-couple 70 S ribosomes.
      Here, we describe the three-dimensional structure of YebU determined by X-ray
      crystallography, and we present a molecular model for how YebU specifically
      recognizes, binds and methylates its ribosomal substrate. The YebU protein has an
      N-terminal SAM-binding catalytic domain with structural similarity to the
      equivalent domains in several other m(5)C RNA MTases including RsmB and PH1374.
      The C-terminal one-third of YebU contains a domain similar to that in
      pseudouridine synthases and archaeosine-specific transglycosylases (PUA-domain),
      which was not predicted by sequence alignments. Furthermore, YebU is predicted to
      contain extended regions of positive electrostatic potential that differ from
      other RNA-MTase structures, suggesting that YebU interacts with its RNA target in
      a different manner. Docking of YebU onto the 30 S subunit indicates that the PUA
      and MTase domains make several contacts with 16 S rRNA as well as with the
      ribosomal protein S12. The ribosomal protein interactions would explain why the
      assembled 30 S subunit, and not naked 16 S rRNA, is the preferred substrate for
      YebU.

PMID- 16793064
TI  - Epileptic polyopia with right temporal lobe epilepsy as studied by FDG-PET and
      MRI: a case report.
AB  - Polyopia is one of rare, visual hallucinations. A 61-year-old man suffered from
      daily episodes of polyopia and generalized convulsions, and he was diagnosed as
      right temporal lobe epilepsy. MRI revealed right amygdalar swelling. FDG-PET
      showed hypometabolism in the right anterior temporal and the mesial occipital
      areas. Polyopia is thought to be caused by dysfunction of updating process of
      visual information in the visual association cortices. It was most likely that,
      in this patient, both mesial temporal and ipsilateral occipital areas were
      responsible for manifesting epileptic polyopia, as ictal onset zone and
      symptomatogenic zone, respectively.

PMID- 16793065
TI  - Repetitive transcranial magnetic stimulation to improve mood and motor function
      in Parkinson's disease.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain
      stimulation technique that can produce lasting changes in excitability and
      activity in cortical regions underneath the stimulation coil (local effect), but
      also within functionally connected cortical or subcortical regions (remote
      effects). Since the clinical presentation of Parkinson's disease (PD) is related
      to abnormal neuronal activity within the basal ganglia and cortical regions,
      including the primary motor cortex, the premotor cortex and the prefrontal
      cortex, several studies have used rTMS to improve brain function in PD. Here, we
      review the studies that have investigated the possible therapeutic effects of
      rTMS on mood and motor function in PD patients. We highlight some methodological
      inconsistencies and problems, including the difficulty to define the most
      effective protocol for rTMS or to establish an appropriate placebo condition. We
      finally propose future directions of research that may help to improve the
      therapeutic efficacy of rTMS in PD.

PMID- 16793066
TI  - Role of P-glycoprotein in tissue uptake of indinavir in rat.
AB  - The effect of p-glycoprotein inhibition on tissue distribution of indinavir, an
      anti-HIV (human immunodeficiency virus) protease inhibitor drug, has been
      evaluated. Indinavir was co-administered intravenously in rats along with a p
      glycoprotein inhibitor, PSC833, and the drug concentrations in plasma and various
      tissues were determined using a HPLC method. Additionally, initial uptake
      clearance of indinavir was evaluated in the brain and testes. The highest
      increasing effect of p-glycoprotein inhibition on the tissue uptake ratios of
      indinavir was found in central nervous system (CNS). The estimated tissue
      extraction the drug was indicative of (i) limited drug entry to brain parenchyma,
      which was increased significantly by p-glycoprotein inhibition, (ii) non
      restricted drug entry to testes, heart and spleen, which was increased
      significantly in the case of heart and decreased in the case of testes and spleen
      as a result of p-glycoprotein inhibition, and (iii) drug accumulation in liver
      and small intestine and, to a lesser extent, kidney, which was not affected by p
      glycoprotein inhibition. The uptake clearances of indinavir by brain parenchyma
      in PSC833-treated and control rats were 68.80+/-8.65 and 21.63+/-4.28 micro/min/g
      and the corresponding values for the testes were 39.84+/-4.90 and 36.65+/-2.54
      microl/min/g. The difference was significant only in the case of brain parenchyma
      (P<0.001). These data showed that p-glycoprotein inhibition increases the CNS
      uptake of indinavir markedly and has some transient minor effects on drug uptake
      by some other tissues.

PMID- 16793067
TI  - Analgesic effects of mGlu1 and mGlu5 receptor antagonists in the rat formalin
      test.
AB  - mGlu1 and mGlu5 receptors have been implicated in pain associated with
      inflammation. In the present study, the formalin test was used to measure
      sustained pain with components of tissue injury. The aims of the present study
      were to assess: (i) the role of mGlu1 and mGlu5 receptors in inflammatory pain
      using selective antagonist EMQMCM, 1.25-5 mg/kg, as the mGlu1 receptor
      antagonist, and MPEP or MTEP, 2.5-10 mg/kg, as mGlu5 receptor antagonist; (ii)
      the possible interaction between mGlu1 and mGlu5 receptor antagonists and
      morphine; and (iii) whether tolerance develops to the analgesic effects of these
      antagonists after prolonged treatment. EMQMCM, MTEP and MPEP significantly
      reduced the manifestation of both phases of formalin response. However, all these
      mGlu receptor antagonists did not affect the withdrawal latencies in a model of
      acute pain (Hargreaves test), which has a different underlying mechanism. In the
      present study, the suppressive effect on formalin-induced pain behaviour was much
      stronger when mGlu1 and mGlu5 receptor antagonists were co-injected compared to
      administration of a single antagonist, but this effect was not seen when mGlu
      receptor antagonist was co-administered with morphine. This is in contrast to the
      pronounced inhibitory effects after co-treatment with morphine and the
      uncompetitive NMDA receptor antagonist memantine. The present study also provides
      the first direct in vivo evidence that prolonged administration of MTEP (5 mg/kg)
      over 7 days leads to the development of tolerance to its antinociceptive effects.
      Such tolerance was not observed when EMQMCM (5 mg/kg) was administered in the
      same manner. In conclusion, these results provide additional arguments for the
      role of group I mGlu receptors in pain with inflammatory conditions.

PMID- 16793068
TI  - Attenuation of nicotine-induced rewarding effects in A2A knockout mice.
AB  - The non-selective A2A antagonist caffeine has been reported to modify nicotine
      induced locomotor and reinforcing effects. In the present study, we have
      investigated the specific role of A2A adenosine receptors in the behavioural
      responses induced by nicotine by using genetically modified mice lacking A2A
      adenosine receptors. Acute nicotine administration induced a similar decrease of
      locomotor activity in A2A knockout mice and wild-type littermates. Acute
      antinociceptive responses elicited by nicotine in the tail-immersion and hot
      plate tests were unaffected in these mutant mice. The rewarding properties of
      nicotine were then investigated using the place-conditioning paradigm. Nicotine
      induced conditioned place preference was suppressed in A2A knockout mice.
      Accordingly, in vivo microdialysis studies revealed that the extracellular levels
      of dopamine in the nucleus accumbens were not increased after nicotine
      administration in mutant mice. Wild-type and A2A knockout mice were trained in
      conditioned taste aversion procedure in which drinking a saccharin or saline
      solution was paired with nicotine or saline injections. A similar reduction in
      the intake of nicotine-paired solution in this paradigm was obtained in both
      genotypes. Finally, the administration of the nicotinic antagonist mecamylamine
      in nicotine-dependent mice precipitated a similar withdrawal syndrome in both
      genotypes. Together, the present results identify A2A adenosine receptors as an
      important factor that contributes to the rewarding properties of nicotine.

PMID- 16793069
TI  - Mu opioid receptor-dependent and independent components in effects of tramadol.
AB  - Tramadol is thought to induce analgesia via both opioid and non-opioid pathways,
      although the precise mechanisms remain to be elucidated. In this study, we
      investigated the roles of the mu-opioid receptor (MOP) in analgesic and rewarding
      effects of tramadol by using MOP knockout (KO) mice. Tramadol-induced
      antinociception, assessed by hot-plate and tail-flick tests, was significantly
      reduced in heterozygous and homozygous MOP-KO mice when compared with that in
      wild-type mice. Interestingly, however, tramadol retained its ability to induce
      significant antinociception in homozygous MOP-KO mice. The tramadol-induced
      antinociception remaining in homozygous MOP-KO mice was not significantly
      affected by methysergide, a serotonin receptor antagonist, but was partially
      blocked by yohimbine, an adrenaline alpha2 receptor antagonist, and both
      naloxone, a non-selective opioid receptor antagonist, and yohimbine. In addition,
      antinociceptive effects of an active tramadol metabolite M1 were abolished or
      remarkably reduced in MOP-KO mice. On the other hand, neither wild-type nor
      homozygous MOP-KO mice showed significant place preference for tramadol in a
      conditioned place preference test, although there were slight tendencies toward
      preference in wild-type mice and avoidance in homozygous MOP-KO mice. These
      results strongly support the idea suggested in the previous pharmacological
      studies that MOP and the adrenaline alpha2 receptor mediate most of the analgesic
      properties of tramadol.

PMID- 16793070
TI  - Estradiol decreases the orexigenic effect of melanin-concentrating hormone in
      ovariectomized rats.
AB  - Estradiol exerts an inhibitory effect on food intake via interactions with
      anorexigenic peptides, like cholecystokinin, that function to decrease meal size.
      It is currently unknown whether estradiol also interacts with orexigenic
      compounds implicated in the physiological control of food intake. Thus, the
      primary goal of this study was to determine whether estradiol decreases the
      orexigenic effect of melanin-concentrating hormone (MCH), a neuropeptide that,
      like estradiol, appears to influence food intake by selectively affecting the
      controls of meal size. Food and water intake were monitored following lateral
      ventricular (icv) infusions of 5 mug MCH or saline vehicle in oil- and estradiol
      treated ovariectomized rats. MCH increased food intake throughout the first 4 h
      of the dark phase in oil-treated rats, but only for the last 2 h of the same 4-h
      interval in estradiol-treated rats. As a result, the orexigenic effect of MCH was
      significantly lower in estradiol-treated rats, relative to oil-treated rats.
      During this interval of MCH-stimulated feeding, a prandial increase in water
      intake was not observed in either oil- or estradiol-treated rats. We conclude
      that estradiol decreases the orexigenic effect of MCH in ovariectomized rats.

PMID- 16793072
TI  - Structure-activity relationship of chemical defenses from the freshwater plant
      Micranthemum umbrosum.
AB  - Vascular plants produce a variety of molecules of phenylpropanoid biosynthetic
      origin, including lignoids. Recent investigations indicated that in freshwater
      plants, some of these natural products function as chemical defenses against
      generalist consumers such as crayfish. Certain structural features are shared
      among several of these anti-herbivore compounds, including phenolic, methoxy,
      methylenedioxy, and lactone functional groups. To test the relative importance of
      various functional groups in contributing to the feeding deterrence of
      phenylpropanoid-based natural products, we compared the feeding behavior of
      crayfish offered artificial diets containing analogs of elemicin (1) and beta
      apopicropodophyllin (2), chemical defenses of the freshwater macrophyte
      Micranthemum umbrosum. Both allyl and methoxy moieties of 1 contributed to
      feeding deterrence. Disruption of the lactone moiety of 2 reduced its deterrence.
      Finally, feeding assays testing effects of 1 and 2 at multiple concentrations
      established that these two natural products interact additively in deterring
      crayfish feeding.

PMID- 16793073
TI  - Four new immunomodulating steroidal glycosides from the stems of Stephanotis
      mucronata.
AB  - Four new C-21 steroidal glycosides, mucronatosides E (1), F (2), G (3), and H
      (4), were isolated from the stems of Stephanotis mucronata. Two of them had the
      rare aglycone with a double bond between C-6 and C-7. Their structures were
      elucidated on the basis of spectroscopic data and chemical evidence. These
      isolated compounds were assayed for their immunological activities in vitro
      against concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced
      proliferation of mice splenocytes. Compounds 2 and 4 showed immunosuppressive
      activities in a dose-dependent manner, while compounds 1 and 3 possessed
      immunoenhancing activities.

PMID- 16793074
TI  - Study on the high power air-coupled ultrasonic compound transducer.
AB  - The high power air-coupled compound ultrasonic transducer in flexural vibration
      is studied. The transducer consists of a sandwich longitudinal piezoelectric
      transducer and a circular thin plate in flexural vibration. The resonance
      frequency equation and the equivalent circuit of a circular radiator with clamped
      boundary condition are derived. The resonance frequency equation and the
      equivalent circuit of the compound transducer are also obtained. The radiated
      acoustic field of the circular thin plate radiator is analyzed and the
      directional pattern is calculated. It can be seen that when the vibrational order
      of the circular thin plate in flexural vibration is increased, the radiated
      acoustic field becomes complex.

PMID- 16793075
TI  - Electrode effects on general modes in high-overtone bulk acoustic resonators.
AB  - Generally, in theoretical calculations of high-overtone bulk acoustic resonators
      (HBAR), metal electrode effects were always ignored. However, the acoustical
      impedance, thickness and loss of the electrodes affect practically the
      performances of HBAR operating at high-frequency. For very high-frequency cases,
      the thickness of the metal electrode is always on the same order of that of the
      piezo-film and the electrode effects on modes cannot be negligible. In this
      paper, based on the resonance frequency spectra and Butterworth Van Dyke
      equivalent circuit of HBAR, the effects of the material, loss, and thickness of
      the electrodes on the figure of merit, effective electromechanical coupling
      factor, quality factor, etc. are analyzed. It is demonstrated that the
      performance of HBAR can also be optimized by using the electrodes with proper
      impedance, loss and thickness.

PMID- 16793076
TI  - Fine grains ceramics of PIN-PT, PIN-PMN-PT and PMN-PT systems: drift of the
      dielectric constant under high electric field.
AB  - Lead-based ferroelectric ceramics with (1-x)Pb(B1 B2)O3-xPbTiO3 formula have
      emerged as a group of promising materials for various applications like
      ultrasonic sonars or medical imaging transducers. (1-x)PMN-xPT, (1-x)PIN-xPT and
      ternary solutions xPIN-yPMN-zPT ceramics are synthesised using the solid state
      reaction method. Our objective is to achieve higher structural transition
      temperatures than those of PMN-PT ceramics with as good dielectric, piezoelectric
      and electromechanical properties. Ceramics capacitance and loss tangent are
      measured when the ac field of measurement increases up to E=500 V/mm. Behaviours
      of these materials under ac field are related to their coercive field and Curie
      temperature.

PMID- 16793077
TI  - A traveling wave ultrasonic motor of high torque.
AB  - A traveling wave ultrasonic motor of high torque with a new configuration is
      proposed in this paper. In the new design, a part of the motor serves as the
      stator. The rotor is the vibrator consisting of a toothed metal ring with
      piezoelectric ceramic bonded, which generates ultrasonic vibration. The rotor is
      in contact with the shell of motor and is driven by the friction between the
      rotor and the stator. This configuration not only removes the rotor in a
      conventional type of traveling wave ultrasonic motor but also changes the
      interaction between the rotor and the stator of the motor so that it improves the
      output performance of the motor. Although an electric brush is added to the
      ultrasonic motor, it is easy to be fabricated because of the low speed of motor.
      The finite element method was used to compute the vibration modes of an
      ultrasonic motor with a diameter of 100mm to optimize the design of the motor. A
      9th mode was chosen as the operation mode with a resonance frequency about 25
      kHz. According to the design, a prototype was fabricated. Its performance was
      measured. The rotation speed-torque curves for various frequencies were obtained.
      The result shows that its stall torque is greater than 4 Nm within a range of 400
      Hz. This ultrasonic motor was used to drive the window glass of a mobile car and
      the result was satisfactory. In the further the research on the friction material
      between the stator and the rotor is under way to improve the efficiency of the
      ultrasonic motor.

PMID- 16793078
TI  - Fringed sound fields and their interaction with liquid-solid interfaces.
AB  - On the one hand, it is well known that Gaussian beams possess the ability to
      stimulate Rayleigh waves, resulting in the Schoch effect, a lateral beam
      displacement. This effect, often characterized by a reflected sound pattern
      consisting of two anti-phase beams, is due to the re-radiation of sound because
      of the stimulation of leaky Rayleigh waves. On the other hand, fringed sound
      beams are characterized by the fact that they consist of a number of neighboring
      anti-phase narrow beams. They are a first approximation of a sound field
      originating from a phased array of harmonic vibrating crystals in which each
      crystal vibrates in anti-phase compared to its neighbor. The individual lobes
      within the fringed sound pattern diverge much less than standard Gaussian beams
      of the same size. The current study investigates the interaction of fringed beams
      with a liquid-solid interface. It is found that under certain conditions, a
      fringed beam, incident at the Rayleigh angle, produces a reflected sound pattern
      that contains a wide lobe that is not fringed. It is also shown that under other
      conditions, contrary to the famous forward displacement of the reflected sound
      for incident Gaussian beams, a strong backward displacement occurs for fringed
      beams.

PMID- 16793079
TI  - Control of an ultrasonic transducer to realize low speed driven.
AB  - This paper deals with the control of a transducer to realize low speed. A new PWM
      control is proposed to fit the transducer. By this control method, the transducer
      is directly excited by pulses whose width can be modulated. The noise induced by
      conventional PWM control is eliminated and the motor works more steadily and more
      quietly. Instead of the general method of decreasing vibrating amplitude of
      ultrasonic motor to realize low speed, in this paper, two fast contrary
      elliptical vibrations of the transducer's two Langevin vibrators are excited to
      restrain skip-slip influence on ultrasonic motor's low speed performance and the
      driven is realized by the difference of the two vibrators' vibrating amplitudes.
      Experiments had been carried out by driving an aerostatic guide and fuzzy control
      is applied. The controlled speed reached 0.1 mm/s.

PMID- 16793080
TI  - Lamb wave propagation in a plate with a grooved surface with several spatial
      periodicities.
AB  - In order to investigate non-destructively the bonding between rough plates, the
      problem of Lamb waves propagating on a rough plate is addressed in this paper.
      Numerical analysis is performed on periodical gratings made of identical
      triangular grooves. If the surface profile is made up of grooves with one
      periodicity, then a mode conversion is observed. In the wave-number/frequency
      space, a phonon relation is written between phonons related to the grating and to
      the incident and reflected-converted modes. If the grooved surface is made up of
      several spatial periodicities, then the phonon relation is still verified. Signal
      processing allows us to give an interpretation of the results in the dual space
      (wave-number/frequency). An experimental study is also performed to corroborate
      the numerical predictions.

PMID- 16793081
TI  - Ultrasonic evaluation of residual stresses in flat glass tempering by an original
      double interferometric detection.
AB  - In industrial thermal tempering of glass, the knowledge of the homogeneity of
      compressive residual stress field on the glass product is fundamental to
      guarantee the quality of the tempered glass product. In this paper, we use the
      acoustoelasticity phenomenon in order to estimate the residual stress
      distribution by using acoustic surface wave. We present an experimental setup
      based on a double interferometric detection in which an aspheric lens is
      associated with a beam splitter and a YAG laser whose power is 100 mW. This
      relative high power enables us to carry out measurements on surface flat glass
      although optical reflection coefficient is typically weak (< 10%). Using these
      two points of detection, the evolution of relative surface wave velocity is
      obtained with a good accuracy. At last, a comparison between the numerical
      modeling and experimental results shows the potentiality of an ultrasonic method
      to estimate stress distribution in flat glass tempering.

PMID- 16793082
TI  - Measurement method of particle concentration and acoustic properties in
      suspension using a focused ultrasonic impulse radiated from a plano-concave
      transducer.
AB  - As a method to measure the concentration and property of a particle suspension,
      we proposed an ultrasonic measurement method using a plano-concave ultrasonic
      transducer. To carry out the experiment, we used a focused ultrasonic impulse
      with a broad frequency bandwidth radiated from the transducer, instead of
      utilizing continuous waves as in the conventional method. By analyzing the
      frequency components of the echo returned from the reflector put at the focal
      region of the transducer in suspension, we measured the concentration, etc., from
      variations of attenuation in the frequency spectrum. As specimens, we used some
      substances containing fine particles for which the acoustic properties or sizes
      are heterogeneous to each other. Specifically, the milk fat included in milk was
      examined in detail to characterize the best-tasting milk. In conclusion, we
      determined that the particle concentration and acoustic properties were easily
      and instantaneously measurable using the frequency spectrum obtained from pulse
      echoes passed through the specimen liquid, and the plano-concave transducer was
      advantageous in these measurements.

PMID- 16793083
TI  - Study on measurement of dispersive characteristics of higher order mode Lamb
      waves.
AB  - The dispersive characteristics of higher order mode Lamb waves (HOMLW) excited by
      interdigital transducers (IDT) are measured and analyzed, which are necessary for
      designing micro-sensor in ultrahigh frequency (UHF). A measurement system is set
      up, in which dispersive characteristics of HOMLW are obtained by the method of
      transform between frequency and time domains. The characteristics of amplitude
      frequency and phase-frequency of Lamb wave are auto-measured by the system. By
      IFFT, the pulse response of the IDT device was obtained. Different modes were
      separated in time domain and dispersive curve of each mode is calculated by FFT.
      The best mode is chosen to design the micro-sensor in UHF. The phase velocity of
      HOMLW is greater than the surface wave (SAW) velocity and an oscillator in higher
      frequency can be made, so the absolute sensitivity of micro-sensor can be
      increased. In this paper, the dispersive characteristics of HOMLW excited by an
      IDT in a 127.86 degrees rotated Y-cut, X propagating lithium niobate plate is
      analyzed. An oscillator using a(13) mode is made, the phase velocity of which is
      measured about 19,652 m/s when h/lambda=0.94 (h=plate thickness,
      lambda=wavelength).

PMID- 16793084
TI  - Process monitoring using ultrasonic sensor systems.
AB  - Continuous in-line measurement of substance concentration in liquid mixtures is
      valuable in improving industrial processes in terms of material properties,
      energy efficiency and process safety. Ultrasonic sensor systems meet the
      practical requirements of a chemical sensor quite well. Currently ultrasonic
      sensor systems are widely used as acoustic chemical sensors to measure
      concentration of selected substances or to monitor the course of polymerisation,
      crystallisation or fermentation processes. Useable acoustic properties for the
      characterisation of liquid mixtures are sound velocity, sound absorption and
      acoustic impedance. This contribution will give a short overview of the state of
      the art and several trends for the use of ultrasonic sensor systems in process
      applications. Novel investigations show the very promising possibility to analyse
      liquid multi-phase mixtures like suspensions, emulsions and dispersions.

PMID- 16793085
TI  - Development of an advanced multimode automatic ultrasonic texture measurement
      system for laboratory and production line application.
AB  - We present work on the development of an ultrasonic texture measurement system
      for sheet metals using non-contact transducers, suitable for use both in the
      laboratory and on the production line. Variation of the velocity of the zero
      order symmetric (S0) Lamb wave is used to determine the crystallographic texture
      of polycrystalline metal sheets ranging in thickness from 0.1 to 3 mm. This
      system features improvements on previous state-of-the-art ultrasonic technology
      in that it probes velocity over a continuous range of angles using only two
      electromagnetic acoustic transducers (EMATs). This is demonstrated to offer a
      significant improvement in accuracy and allows the detection and investigation of
      asymmetric anisotropies in the sheets. Another advantage of the system is its
      potential for combining several different measurements using a single pair of
      transducers. The capability is demonstrated for through-thickness shear wave
      measurements as well as the zero-order symmetric Lamb wave measurements which are
      the primary means of determining the texture. The change between generating Lamb
      and through-thickness bulk waves can be made entirely by changing the electrical
      circuit connected to the EMATs without modifying the transducer assembly in any
      way. Measurement of all of the above waves can provide information on the sheet
      thickness and other physical properties of the sheet in addition to texture.
      Certain texture parameters can be calculated from both Lamb and shear wave
      velocities, allowing self-calibration of the system.

PMID- 16793086
TI  - Sonoluminescing single bubble in concentrated alkali halide solutions.
AB  - Single-bubble sonoluminescence is generated in concentrated aqueous solutions of
      LiBr and LiCl. The moving-bubble state, a type of unstable state in which
      sonoluminescence is still emitted, is observed above the stable-sonoluminescence
      state similarly to that in aqueous solutions of NaCl and KCl. Luminosity is
      increased at similar magnitudes for LiBr, LiCl, NaCl and KCl of the same
      concentration.

PMID- 16793087
TI  - High frequency broadband PZT thick film ultrasonic transducers for medical
      imaging applications.
AB  - A modified sol-gel method is used to prepare PZT thick film on Pt-coated silicon
      substrate. A new method of vacuum filling sol-gel precursor solution is
      introduced to improve film quality. The effects of the filling on PZT thick film
      structure and ferroelectric properties are discussed. The fabrication of a high
      frequency transducer with the PZT film as the actuating layer is described. The
      performance of the transducer is measured and results show that the transducer
      backed by E-Solder without a matching layer has a center frequency of 103 MHz and
      a bandwidth of 70%. Beam profile measurements show that the transducer has an
      axial resolution of 9.2 microm and a lateral resolution of 33 microm.

PMID- 16793088
TI  - Power ultrasound interaction with DC atmospheric pressure electrical discharge.
AB  - The effect of power ultrasound application on DC hollow needle to plate
      atmospheric pressure electrical discharge enhanced by the flow of air through the
      needle electrode was studied experimentally. It was found that applying
      ultrasound increases discharge volume. In this volume take place plasmachemical
      processes, used in important ecological applications such as the production of
      ozone, VOC decomposition and de-NOx processes enhancement. In our experiments we
      used a negatively biased needle electrode as a cathode and a perpendicularly
      placed surface of the ultrasonic resonator--horn--as an anode. To demonstrate the
      effect of ultrasound waves on electrical discharge photographs of the discharge
      for the needle to the ultrasonic resonator at distances of 4, 6 and 8mm are
      shown. By varying the distance between needle and the surface of the transducer,
      we were able to create the node or the antinode at the region around the tip of
      the needle, where the ionization processes are effective. In our experimental
      arrangement the amplitude of acoustic pressure at antinode exceeded 10(4) Pa. The
      photographs reveal that the diameter of the discharge on the surface of the
      ultrasonic horn is increased when ultrasound is applied. The increase of
      discharge volume caused by the application of ultrasound can be explained as a
      combined effect of the change of the reduced electric field E/n (E is electric
      field strength and n is the neutral particles density), strong turbulence of the
      particles in the discharge region caused by quick changes of amplitudes of the
      standing ultrasonic wave and finally by the boundary layer near the ultrasonic
      transducer perturbations due to vibrations of the transducer surface.

PMID- 16793089
TI  - Enhanced anisotropy in Paratellurite for inhomogeneous waves and its possible
      importance in the future development of acousto-optic devices.
AB  - The anisotropic feature of most crystals, involves a direction dependent wave
      velocity for each of the possible modes. Paratellurite (Tellurium dioxide) is
      extraordinary because, for one of the propagation modes, i.e. the quasi shear
      horizontal (QSH) mode, the anisotropy is exceptional. This results, on the one
      hand in a very strong directional dependent sound velocity and on the other hand,
      in a low wave velocity in certain directions, resulting in a high figure of merit
      for the acousto-optical interaction. In the case of inhomogeneous waves, the
      slowness surfaces change their shape and magnitude, for all crystals. However,
      for paratellurite, this effect is again extraordinary. As soon as a relatively
      small inhomogeneity is considered, the sound velocity for the QSH mode becomes
      really exceptionally anisotropic, resulting in a slowness surface that is almost
      spherical, covered by pins. The velocity corresponding to those 'pins', is much
      lower than in the case of homogeneous plane waves, which is very promising for
      the future development of acousto-optic cells involving an even higher figure of
      merit.

PMID- 16793090
TI  - Analysis of optodynamic sources generated during laser-induced breakdown in
      water.
AB  - We propose a method for evaluating the size of the laser-induced breakdown region
      in water based on the detection and analysis of optodynamic waves. The breakdown
      region is an optodynamic source of pressure waves that propagate into the
      surrounding liquid as an ultrasonic pulse. In the experiment the optical
      breakdown was generated by a standard ophthalmic Nd:YAG laser with a pulse
      duration of 10 ns and a maximum energy per pulse of 10 mJ. The pulses were
      detected inside the liquid with a laser-beam deflection probe. The waveforms were
      captured in the far-field and analyzed. The analysis provides information about
      the apparent size of the optodynamic source, which is directly related to the
      size of the breakdown region. The proposed method can be adapted for online
      monitoring.

PMID- 16793091
TI  - A study on the dispersions of piezoelectric plate with laser ultrasound
      measurement and theoretical modeling.
AB  - This research is focused in the measurement and modeling for the dispersion
      relations of Lamb waves propagating in LiNbO(3) and LiTaO(3) plates. A
      theoretical model based on a stiffness matrix method with recursion computation
      algorism is used to provide numerical calculations for the dispersion relations.
      Also, a dry, noncontact laser ultrasound technique is used to measured dispersion
      multi-mode dispersion relations. For all the experiments, the measured dispersion
      curves show good agreement with the theoretical calculation, indicating the
      reliabilities in the measurement and modeling.

PMID- 16793092
TI  - Optodynamic study of multiple pulses micro drilling.
AB  - This paper describes an analysis of pulsed lasers micro-drilling of different
      metals. Study focuses to an optodynamic phenomenon which appears as thermal
      effects induced by laser light pulses and leads to dynamic process manifested as
      ultrasonic shock waves propagating into the sample material. The shock waves are
      detected by a non-contact optical method by using arm compensated Michelson.
      Monitoring of the main parameters of the micro drilling such as material ablation
      rate and efficiency was realized by analysis of the optodynamic signals. The
      process is characterized by decreasing ablation rate that leads to the finite
      hole depth. The experimental part of study comprehends a comparison between
      various metals. In order to describe decreasing ablation rate a theoretical model
      based on the energy balance is proposed. It considers the energy/heat transfer
      from the laser beam to the material and predicts a decreasing drilling rate with
      an increasing number of successive laser pulses. According to the proposed model,
      the finite depth of the hole appears as a consequence of the increasing surface
      area through which the energy of the laser beam is conducted away to the material
      around the processed area. Decreasing ablation rate and the finite hole depth
      predicted by model were in good agreement with the experimental results.

PMID- 16793093
TI  - Acoustic field excited by a pulsed laser line source in a cylinder.
AB  - The excitation and propagation of the acoustic waves in an elastic cylinder are
      studied by laser ultrasonics both theoretically and experimentally. The
      theoretical analysis of the two-dimensional acoustic field excited by a pulsed
      laser line source impacting on the generatrix of an elastic cylinder is
      presented. The dispersive properties for both cylindrical Rayleigh wave and the
      higher modes--whispering gallery (WG) modes are analyzed in detail. The numerical
      transient displacement waveforms for a detecting point located another terminal
      of the cylinder diameter opposite the source are calculated. The experimental
      excitation and detection of the acoustic waves in an aluminum cylinder are
      carried out on a laser ultrasonic system, which mainly consists of a Q-switched
      Nd:YAG laser and a laser interferometer. The wave components of bulk waves and
      surface waves (cylindrical Rayleigh waves and WG modes) are analyzed by comparing
      the numerical and experimental waveforms. The results are in good agreement.

PMID- 16793094
TI  - The study of guided waves in surfaces and thin supported films using surface
      Brillouin scattering and acoustic microscopy.
AB  - This paper reviews the use of surface Brillouin scattering (SBS) and acoustic
      microscopy (AM) in studying the surface dynamics of solids in order to obtain
      information about the near-surface elastic properties of solids and thin
      supported films. The vibrational modes that are probed by these means include
      Rayleigh surface and pseudo-surface acoustic waves, longitudinal lateral waves
      (surface skimming bulk longitudinal waves) and various thin film guided modes,
      such as Sezawa and Love waves. SBS is the inelastic scattering of light, mediated
      by thermodynamic fluctuations in the surface elevation and near surface elastic
      strains. The scattering cross-section is conveniently expressed in terms of
      Fourier domain elastodynamic Green's functions. AM depends on the insonification
      of a surface through a coupling fluid, and the resulting excitation and
      subsequent decay of the various surface modes. The complex reflectivity of the
      fluid-loaded surface, and the line and point force surface Green's functions are
      invoked in the interpretation of different modalities of AM, yielding much the
      same information about the surface dynamics. The focus in this paper is on the
      Green's function approach. A number of illustrative examples, drawn from the
      authors' research, are provided.

PMID- 16793095
TI  - Three-dimensional analyses of photo-modulated reflectivity for transparent
      film/opaque substrate structures.
AB  - For a structure consisting of a transparent film deposited on an opaque substrate
      radiated by a modulated focused laser beam, a 3-D model is established to
      calculate the temperature distributions. Then based on 3-D thermoelastic
      displacements and dielectric constants depended on the temperature of the bilayer
      structure, the photo-modulated reflectivity of the structure is calculated by
      using FEM method. As an example, the modulated reflectance variations with the
      modulation frequency of the optical beam and the thermal conductivity of the film
      in ZnO/Si bilayer structures are also obtained.

PMID- 16793096
TI  - Modeling laser-generated guided waves in bonded plates by the finite element
      method.
AB  - The purpose of this research is to develop an effective model of the transient
      laser-generated guided waves in bonded plates by the finite element (FE) method.
      The FE parameters, such as the mesh density and the time step size, which are
      related to wave propagation, are optimized in order to set up a standard, and the
      correlation between these parameters is discussed. The waveforms in bonded plates
      with different bonded interface modeled by the spring model are obtained and then
      compared. The results show that the transient responses are sensitive to the
      stiffness coefficients characterizing the cohesive quality. Finally, these FE
      results are compared with analytical and experimental results. All these
      comparisons confirm the accuracy of the FE method for modeling laser-generated
      guided waves in bonded plates.

PMID- 16793097
TI  - A miniaturization of the multi-degree-of-freedom ultrasonic actuator using a
      small cylinder fixed on a substrate.
AB  - Multi-degree-of-freedom ultrasonic actuator has been studied for robot arms and
      multidimensional precision table and so on because of its simple structure,
      silent operation, and holding force. In this study, we aim to miniaturize multi
      degree-of-freedom ultrasonic actuator for fabrication on a substrate. This
      actuator consists of a stainless steel cylinder and a PZT ring. The cylinder is
      fixed on a substrate and the PZT ring is glued to the substrate near the
      cylinder. The 1st longitudinal vibration and the 2nd bending vibration are
      simultaneously excited in the cylinder to make elliptical motion at the top of
      the cylinder and a ball rotor placed on the cylinder rotates because of the
      friction force. Length of the cylinder was decided so as to tune the resonance
      frequency of the 1st longitudinal vibration to the 2nd bending one. Actuator
      performances are evaluated experimentally using a 14 mm height and 7 mm diameter
      stainless steel cylinder with a 0.5 mm thickness PZT ring. The rotation about the
      cylinder axis is tested using the two orthogonal bending vibrations with 90
      degrees phase difference. Also, the rotation about horizontal axes were
      investigated using the combination of the longitudinal vibration and one of two
      bending vibrations. We measured the rotation speed of a steel ball and obtained
      15.8 rps using a 6 mm diameter ball rotor.

PMID- 16793098
TI  - A novel approach for description of nonlinear field radiated from a concave
      source with wide aperture angle.
AB  - A new approach is proposed to study the nonlinear sound field radiated from a
      concave spherical source with a wide aperture angle. The nonlinear sound field is
      theoretically described by a set of equations deduced reversely from the second
      order Westervelt nonlinear wave equation. To examine the validity of the
      theoretical model, numerical calculations are performed on a concave spherical
      radiator with the aperture angle wide up to 40 degrees. Numerical calculation is
      implemented by the finite difference time domain algorithm in the oblate
      spheroidal coordinate system. Numerical results are in agreement with those
      obtained by Kamakura's solutions.

PMID- 16793099
TI  - Cymbal piezoelectric composite underwater acoustic transducer.
AB  - The working principle of Cymbal piezoelectric composite underwater acoustic
      transducer was studied in this paper. PZT-5A piezoelectric ceramic disk was used
      as piezoelectric phase and brass foil was used as end cap electrode of the Cymbal
      transducer. The silicon rubber was used as the insulated proof layer of the
      underwater acoustic transducer. The properties of this transducer used as
      hydrophone, such as operation frequency, free-field voltage receiving sensitivity
      and directivity, were investigated. Several kinds of prototype of this transducer
      were fabricated and the properties of this transducer used as hydrophone were
      tested. The results show that the properties of this transducer used as
      hydrophone depend on the dimensions of Cymbal transducer because the
      piezoelectric properties of this transducer are dependent on the dimensions of
      Cymbal transducer's end caps. The appropriate dimensions for getting higher free
      field voltage receiving sensitivity with -184.7 dB were obtained.

PMID- 16793100
TI  - Location of multiple proximate flaws using perpendicular NDT ultrasonic arrays.
AB  - An improved method for ultrasonic location of multiple flaws using perpendicular
      ultrasonic arrays, working in near-field conditions, is presented. The method
      uses the pulse-echo technique and is based on the processing of the information
      acquired by both the elemental emitting transducers and their adjacent ones. This
      type of processing improves the performance of a previous method that sometimes
      presents limitations for the detection of multiples flaws. This new method is
      applied to a set of ultrasonic traces, obtained with an ultrasonic prototype
      specifically designed for testing this method, showing the improvement obtained
      in imaging results.

PMID- 16793101
TI  - Coupling mechanism of an EMAT.
AB  - Electro-magnetic acoustic transducers (EMATs) generate ultrasonic waves in metals
      through an electromagnetic coupling mechanism. A concept for EMAT generation,
      using a coil alone without a permanent magnet, but with a pulse generator and a
      sample, is introduced. A simplified equivalent coil circuit is given, and has
      been validated by experimental measurements. Such an equivalent circuit is useful
      for excitation current calculations, which have often been neglected in previous
      publications in this area but have proved to be of great importance in
      considering the efficiency and frequency characteristics of ultrasonic
      generation. Due to the coil sample coupling, the equivalent coil inductance is
      dependent on the electrical conductivity and magnetic permeability of the metal
      sample, the lift-off, the coil orientation relative to the metal sample and the
      coil configuration. The use of a coil alone to generate ultrasound has limited
      applications as a suitable ultrasonic detector must also be used, but where
      appropriate this type of generation source provides a robust, non-contact and
      inexpensive means of ultrasonic generation without worrying the permanent magnet
      attracting ferromagnetic particles that can prevent from practical on-line
      application of EMATs.

PMID- 16793102
TI  - Sonophotocatalysis of oxalic acid solution.
AB  - Sonophotocatalysis of oxalic acid was performed in various atmospheric
      conditions. Sonophotocatalysis means a coupled reaction of sonolysis and
      photocatalysis. CO(2), CO and H(2) were obtained. The yield of CO(2) was twice
      larger than the sum of yields of photocatalysis and sonolysis in an Ar
      atmosphere. Namely, synergistic effect was observed. Further improvement was
      observed after pre-sonication. Hydrogen peroxide produced during sonication is a
      key material for the synergistic effect. In surroundings including O(2), however,
      synergistic effect could not be observed. The role of ultrasonic waves on the
      sonophotocatalysis of organic compounds was investigated.

PMID- 16793103
TI  - Ultrasonic micro-motor using miniature piezoelectric tube with diameter of 1.0
      mm.
AB  - At the present moment, the smallest piezoelectric ultrasonic micro-motors
      utilizing miniature PZT piezoelectric ceramic tubes were developed. The motor
      consists of a PZT-metal composite tube stator, two steel rotors and a thin shaft
      that keeps the two rotors pressing on both ends of the stator elastically. The
      dimensions of the PZT tube are 1.0 mm in outer diameter, 0.6 mm in inner diameter
      and 5.0 mm in length. The diameter and total length of the assembled micro-motor
      is 1.0 mm and 8 mm (including an adjusting spring), respectively. The tube-type
      micro-motor is driven by two pairs of alternative voltages with phase shift 90
      degrees between the adjacent electrodes and operated in the first circular
      bending vibration mode of the stator with the resonance frequency about 58 kHz.
      The experimental results show that the tube-type micro-motors have perfect
      performances: (i) high rotation frequency over 3000 rpm and (ii) large starting
      torque over 7.8 microN m under the conditions of the input voltage of 110 V(p-p)
      and the resonance frequency. The micro-motor is well suitable for operating in
      micro-spaces, such as in intravascular, micro-robots and micro-craft
      applications.

PMID- 16793104
TI  - A miniature ultransonic pump using a bending disk transducer and a gap.
AB  - It is known that if a pipe end is faced at a vibrating surface in liquid with a
      small gap, liquid is suctioned into the pipe. As a miniature configuration, we
      introduce a bending disk transducer 30 mm in diameter using a ring-shaped PZT
      element. The disk vibrator is worked at the fundamental resonance frequency of 19
      kHz of the bending mode. To optimize the pipe geometry, we experimentally
      investigated the effect of the outer diameter on the pump performance. As a
      result, the outer/inner diameter ratio of 3:2 is optimum for the gap smaller than
      20 microm. We achieved the maximum pump pressure of 14.8 kPa and the maximum flow
      rate of 10 ml/min. using the prototype pump.

PMID- 16793105
TI  - Performance optimization of plate-mode sensors with bi-layered structure.
AB  - The acoustic characteristics of plate-mode sensors with bi-layered structures
      composed of a piezoelectric film and a non-piezoelectric substrate are studied by
      numerical calculations using the transfer matrix method. Performances of the
      sensors can be evaluated based on the theoretical calculations of the dispersion
      curves, electromechanical coupling coefficients and sensitivities of the plate
      mode sensors with a bi-layered structure. In order to obtain the optimized
      operating conditions of the sensors, the operating mode, frequency and the ratios
      of thickness of piezoelectric film to that of the substrate are evaluated when
      the sensors are applied in gas and/or liquid conditions.

PMID- 16793106
TI  - Resonant transmission in stop bands of acoustic waves in periodic structures.
AB  - Acoustic resonant transmission (RT) phenomenon found in Bragg couplers made of
      alternatively high (H) and low (L) impedance materials is theoretically
      investigated. The existence of the RT within the Bragg stop bands is analytically
      demonstrated, along with the exact peak values expressed in closed form in terms
      of the coupler parameters. RT takes place either when the coupler is terminated
      with an L-layer and has its bottom surface free, or when it is terminated with an
      H-layer and the bottom clamped. Numerical results are given for the transmission
      and reflection rates in Bragg couplers made of tungsten and SiO(2) layers.

PMID- 16793107
TI  - Acoustical experiment of yogurt fermentation process.
AB  - One of the important factors through food manufacturing is hygienic management.
      Thus, food manufactures prove their hygienic activities by taking certifications
      like a Hazard Analysis and Critical Control Point (HACCP). This concept also
      applies to food monitoring. Acoustical measurements have advantage for other
      measurement in food monitoring because they make it possible to measure with
      noncontact and nondestructive. We tried to monitor lactic fermentation of yogurt
      by a probing sensor using a pair of acoustic transducers. Temperature of the
      solution changes by the reaction heat of fermentation. Consequently the sound
      velocity propagated through the solution also changes depending on the
      temperature. At the same time, the solution change its phase from liquid to gel.
      The transducers usage in the solution indicates the change of the temperature as
      the change of the phase difference between two transducers. The acoustic method
      has advantages of nondestructive measurement that reduces contamination of food
      product by measuring instrument. The sensor was inserted into milk with lactic
      acid bacterial stain of 19 degrees C and monitored phase retardation of
      propagated acoustic wave and its temperature with thermocouples in the mild. The
      monitoring result of fermentation from milk to Caspian Sea yogurt by the acoustic
      transducers with the frequency of 3.7 MHz started to show gradient change in
      temperature caused by reaction heat of fermentation but stop the gradient change
      at the end although the temperature still change. The gradient change stopped its
      change because of phase change from liquid to gel. The present method will be
      able to measure indirectly by setting transducers outside of the measuring
      object. This noncontact sensing method will have great advantage of reduces risk
      of food contamination from measuring instrument because the measurement probes
      are set out of fermentation reactor or food containers. Our proposed method will
      contribute to the hygienization for the food manufacture industry.

PMID- 16793108
TI  - Measurement of the viscosity-density product using multiple reflections of
      ultrasonic shear horizontal waves.
AB  - We have developed an on-line computer-controlled sensor, based on ultrasound
      reflection measurements, to determine the product of the viscosity and density of
      a liquid or slurry for Newtonian fluids and the shear impedance of the liquid for
      non-Newtonian fluids. A 14 MHz shear wave transducer is bonded to one side of a
      45-90 degrees fused silica wedge and the base is in contract with the liquid.
      Twenty-eight echoes were observed due to the multiple reflections of an
      ultrasonic shear horizontal (SH) wave within the wedge. The fast Fourier
      transform of each echo was obtained for a liquid and for water, which serves as
      the calibration fluid, and the reflection coefficient at the solid-liquid
      interface was obtained. Data were obtained for 11 sugar water solutions ranging
      in concentration from 10% to 66% by weight. The viscosity values are shown to be
      in good agreement with those obtained independently using a laboratory
      viscometer. The data acquisition time is 14s and this can be reduced by judicious
      selection of the echoes for determining the reflection coefficient. The
      measurement of the density results in a determination of the viscosity for
      Newtonian fluids or the shear wave velocity for non-Newtonian fluids. The sensor
      can be deployed for process control in a pipeline, with the base of the wedge as
      part of the pipeline wall, or immersed in a tank.

PMID- 16793109
TI  - Molecular epidemiology of the HHV-8 K1 gene from Moroccan patients with Kaposi's
      sarcoma.
AB  - The genetic variability of the human herpesvirus 8 (HHV-8) strains circulating in
      the populations living in the Maghreb region, an endemic area for HHV-8 and
      associated Kaposi's sarcoma, remains largely unknown. We have thus analyzed the
      genetic variation of the complete K1 gene of HHV-8 in a series of 35 viral
      strains, originating from 28 Moroccan patients with classic, AIDS-associated or
      iatrogenic Kaposi's sarcoma lesions. All but one of the 35 strains belonged to
      the large C molecular subtype. Furthermore, high genetic diversity within the C
      subtype was observed in the 35 sequenced HHV-8 K1 genes, with strains belonging
      to several and distinct subgroups highly supported from a phylogenetically
      viewpoint (e.g., C3, C7, C'' and C5). Considering these newly identified Moroccan
      viral strains in the context of 189 complete K1 genes, we were able to
      characterized, using the Simplot program, two main groups of recombinant chimeric
      K1 genes, either intertypic (C5) or intratypic (C7). In addition, the genetic
      characterization of the host maternal gene pool, through the analyses of mtDNA
      variation, did not provide evidence for any association between a particular
      human ethno-geographic background (i.e., North African vs. sub-Saharan African
      vs. West Eurasian linages) and any HHV-8 strain because both C' and C'' strains
      were randomly distributed among the different patients' population backgrounds.

PMID- 16793110
TI  - Recombinant adeno-associated virus expressing the receptor-binding domain of
      severe acute respiratory syndrome coronavirus S protein elicits neutralizing
      antibodies: Implication for developing SARS vaccines.
AB  - Development of an effective vaccine for severe acute respiratory syndrome (SARS)
      remains to be a priority to prevent possible re-emergence of SARS coronavirus
      (SARS-CoV). We previously demonstrated that the receptor-binding domain (RBD) of
      SARS-CoV S protein is a major target of neutralizing antibodies. This suggests
      that the RBD may serve as an ideal vaccine candidate. Recombinant adeno
      associated virus (rAAV) has been proven to be an effective system for gene
      delivery and vaccine development. In this study, a novel vaccine against SARS-CoV
      was developed based on the rAAV delivery system. The gene encoding RBD was cloned
      into a pAAV-IRES-hrGFP plasmid. The immunogenicity induced by the resulting
      recombinant RBD-rAAV was evaluated in BALB/c mice. The results demonstrated that
      (1) a single dose of RBD-rAAV vaccination could induce sufficient neutralizing
      antibody against SARS-CoV infection; (2) two more repeated doses of the
      vaccination boosted the neutralizing antibody to about 5 times of the level
      achieved by a single dose of the immunization and (3) the level of the antibody
      continued to increase for the entire duration of the experiment of 5.5 months.
      These results suggested that RBD-rAAV is a promising SARS candidate vaccine.

PMID- 16793111
TI  - Persistence of fecal indicator bacteria in Santa Monica Bay beach sediments.
AB  - Monitoring the water quality of recreational beaches is only one step toward
      understanding microbial contamination -- the primary cause of beach closings. The
      surf zone sediment reservoir is typically overlooked and may also be important.
      This study involved monitoring the fecal indicator bacteria (FIB) levels in water
      and sediment at three ocean beaches (two exposed and one enclosed) during a storm
      event, conducting laboratory microcosm experiments with sediment from these
      beaches, and surveying sediment FIB levels at 13 beaches (some exposed and some
      enclosed). Peaks in Escherichia coli and enterococci concentrations in water and
      sediment coincided with storm activity at the two exposed beaches, while levels
      of both FIB were consistently high and irregular at the enclosed beach. Results
      from microcosm experiments showing similar, dramatic growth of FIB in both
      overlying water and sediment from all beaches, as well as results from the beach
      survey, support the hypothesis that the quiescent environment rather than
      sediment characteristics can explain the elevated sediment FIB levels observed at
      enclosed beaches. This work has implications for the predictive value of FIB
      measurements, and points to the importance of the sediment reservoir.

PMID- 16793112
TI  - Degradation and detoxification of acetochlor in soils treated by organic and
      thiosulfate amendments.
AB  - This work investigated the degradation and detoxification of acetochlor in a soil
      amended with an organic fertilizer or sodium thiosulfate (STS). Over an
      incubation period of 28 d, the residual acetochlor was measured, soil
      dehydrogenase activity was determined, and major degradates were identified.
      Results show that high-concentration acetochlor was persistent in the soil, as
      indicated by the depression in soil dehydrogenase activity. When the soil was
      amended with the organic fertilizer, the soil dehydrogenase activity was
      stimulated by supplemented nutrients, which resulted in a higher degradation of
      acetochlor. While STS did not significantly stimulate the soil dehydrogenase
      activity, acetochlor degraded more rapidly in STS-amended soil than in organic
      amended soil. The Wright-Hobbie plots show that the influence of initial
      acetochlor concentration on degradation was dependent on the amendments. While
      the organic amendment resulted in the same degradate of acetochlor ethanesulfonic
      acid as in unamended soil, the STS amendment produced dechlorinated acetochlor
      thiosulfonic acid. The degradation of acetochlor in organic- and STS-amended
      soils thus occurred via different mechanisms. Further tests show that both
      degradates were less toxic to green algae than acetochlor. Both organic and STS
      amendments thus effectively degrade and detoxify acetochlor in soils.

PMID- 16793113
TI  - Catalytic activity of Ru/Al2O3 for ozonation of dimethyl phthalate in aqueous
      solution.
AB  - With dimethyl phthalate as the model pollutant and Ru/Al(2)O(3) as catalyst, this
      paper systemically investigates the removal of total organic carbon (TOC) of
      system. Our results have confirmed that Ru/Al(2)O(3) can significantly increase
      the effect of ozonation. TOC removal in 120 min can reach 72% while only 24% with
      ozone alone. The optimal catalyst preparing condition was 0.1 wt% Ru content, 600
      degrees C calcination temperature, 0.5-1.0mm particle diameter, which is
      characterized by a high surface area and a large population of surface active
      sites. The contrasting experiments of ozone alone, catalyst adsorption after
      ozonation, and catalytic ozonation confirmed that catalytic reaction was the most
      important process to TOC removal in system with Ru/Al(2)O(3) as catalyst.

PMID- 16793114
TI  - Characterization and source identification of polycyclic aromatic hydrocarbons
      (PAHs) in the urban environment of Delhi.
AB  - This paper reports on polycyclic aromatic hydrocarbons (PAHs) in the atmospheric
      particulate matter of Jawaharlal Nehru University campus, an urbanized site of
      New Delhi, India. Suspended particulate matter samples of 24h duration were
      collected on glass-fiber filter paper for four representative days in each month
      during January 2002 to December 2003. PAHs were extracted from filter papers
      using toluene with ultrasonication method and analysed. Quantitative measurements
      of polycyclic aromatic hydrocarbons (PAHs) were carried out using the gas
      chromatography technique. The annual average concentration of total PAHs were
      found to be 668+/-399 and 672+/-388 ng/m3 in the years 2002 and 2003,
      respectively. The seasonal average concentrations were found to be maximum in
      winter and minimum during in the monsoon. The results of principal component
      analysis (PCA) indicate that diesel and gasoline driven vehicles are the
      principal sources of PAHs in all the seasons. In winter coal and wood combustion
      also significantly contribute to the PAH levels.

PMID- 16793115
TI  - PCDD/DF concentrations at the inlets and outlets of wet scrubbers in Korean waste
      incinerators.
AB  - To further understand the effects of wet scrubbers on PCDD/DF levels, it was
      measured the concentrations of PCDD/DF, dust, and other gaseous pollutants at
      both the inlets and the outlets of seven wet scrubbers. As a result, the
      concentrations of PCDD/DF at the inlets and outlets of the wet scrubbers ranged
      from 0.2 to 37.4, and 0.8 to 6.0 ng TEQ N m-3, respectively. With the exceptions
      of wet scrubbers F and G, the PCDD/DF levels decreased by and large in most wet
      scrubbers. It was thought that their relatively high removal efficiencies were
      more increased with heavier loads of dust and particle-bound PCDD/DF. On the
      other hand, it was also surveyed the increase of gaseous PCDD/DF in wet scrubber,
      where the total level of PCDD/DF was decreased. However, it was not sure whether
      it had been resulted from the thermal adsorption/desorption phenomenon between
      packing materials and emission gases or not. At the very least, however, although
      there still remains an unexplained aspect for the increase of gaseous PCDD/DF, it
      is clear that wet scrubbers can be sufficiently applied to remove PCDD/DF to a
      certain extent, if only removal efficiencies for the particle loads are high, and
      if a significant part of the PCDD/DF at the inlets is particle associated.

PMID- 16793116
TI  - Historical and geographical aspects of the increasing perfluorooctanoate and
      perfluorooctane sulfonate contamination in human serum in Japan.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) have recently
      received attention due to their widespread contamination in the environment, as
      well as in wildlife and humans. We measured the PFOS and PFOA concentrations in
      historically recorded human serum samples at an age range between 20 and 59 years
      collected in Kyoto, 20 persons per each time point (n=100), and also the PFOS and
      PFOA concentrations in human serum samples at an age range between 20 and 59
      years from 10 locations throughout Japan (n=200). The historical samples
      collected from 1983 to 1999 demonstrated that the PFOA concentrations in males
      and females from Kyoto have increased 4.4-fold and 4.3-fold at a rate of increase
      of 0.49 ng/ml/year and 0.42 ng/ml/year, respectively. In contrast, serum
      concentrations of PFOS reached a plateau in the late 1980s. There are also
      regional differences in both the PFOS and PFOA serum concentrations. The
      concentrations in serum [geometric mean (geometric standard deviation)] (ng/ml)
      in 2003-2004 ranged from 7.6(1.6) in the town of Matsuoka in Fukui prefecture to
      27.8(1.6) in Kyoto city, and ranged from 2.3(1.5) in Matsuoka to 14.5(1.3) in
      Osaka city for PFOS and PFOA, respectively.

PMID- 16793117
TI  - Distribution of lead in urban roadway grit and its association with elevated
      steel structures.
AB  - In an effort to determine the source of exterior lead contamination, we
      investigated the concentration of lead in roadway grit along major thoroughfares
      in New York City and in certain areas under elevated steel structures supporting
      elevated rails. Such structures represent only one source of lead in roadway
      grit. While data revealed that the median lead concentration in roadway grit did
      not exceed the standard for a lead hazard in bare residential soil in any
      borough, the limit of 400 microg/g was exceeded 22%, 18%, 10.5%, and 7.7% of the
      time in Manhattan, Brooklyn, The Bronx, and Queens, respectively. The second part
      of the study revealed the presence of high concentrations of lead in roadway grit
      directly under elevated steel structures. The differences in the concentration of
      lead in roadway grit under steel structures in comparison to areas in NYC not
      near elevated rails was statistically significant. Of the eight sites studied
      from 225 total samples, the median roadway grit lead level was 340 ppm, while the
      level under steel structures was 1480 ppm. Preliminary efforts to determine
      particle size distribution revealed that 84% of the particles were in the range
      of 125-500 microm, but the highest concentration of lead was in the smallest
      fraction analyzed (<63 microm). Lead contamination of roadway grit from
      restoration of elevated painted steel structures is a public health problem as
      these lead particulates get re-suspended in the ambient environment and are
      wafted and tracked into residences.

PMID- 16793118
TI  - Motor alterations associated with exposure to manganese in the environment in
      Mexico.
AB  - Overexposure to manganese (Mn) causes neurotoxicity (a Parkinson-like syndrome)
      or psychiatric damage ("manganese madness"). Several studies have shown
      alterations to motor and neural behavior associated with exposure to Mn in the
      workplace. However, there are few studies on the effects of environmental
      exposure of whole populations. We studied the risk of motor alterations in people
      living in a mining district in Mexico. We studied 288 individual people (168
      women and 120 men) from eight communities at various distances from manganese
      extraction or processing facilities in the district of Molango. We measured
      manganese concentrations in airborne particles, water, soil and crops and
      evaluated the possible routes of Mn exposure. We also took samples of people's
      blood and determined their concentrations of Mn and lead (Pb). We used "Esquema
      de Diagnostico Neuropsicologico" Ardila and Ostrosky-Solis's neuropsychological
      battery to evaluate motor functions. Concentrations of Mn in drinking water and
      maize grain were less than detection limits at most sampling sites. Manganese
      extractable by DTPA in soils ranged between 6 and 280 mg kg(-1) and means were
      largest close to Mn extraction or processing facilities. Air Mn concentration
      ranged between 0.003 and 5.86 microg/m(3); the mean value was 0.42 microg/m(3)
      and median was 0.10 microg/m(3), the average value (geometric mean) resulted to
      be 0.13 microg/m(3). Mean blood manganese concentration was 10.16 microg/l, and
      geometric mean 9.44 microg/l, ranged between 5.0 and 31.0 mcrog/l. We found no
      association between concentrations of Mn in blood and motor tests. There was a
      statistically significant association between Mn concentrations in air and motor
      tests that assessed the coordination of two movements (OR 3.69; 95% CI 0.9,
      15.13) and position changes in hand movements (OR 3.09; CI 95% 1.07, 8.92). An
      association with tests evaluating conflictive reactions (task that explores
      verbal regulations of movements) was also found (OR 2.30; CI 95% 1.00, 5.28). It
      seems from our results that people living close to the manganese mines and
      processing plants suffer from an incipient motor deficit, as a result of their
      inhaling manganese-rich dust.

PMID- 16793119
TI  - Increased basal platelet activity, plasma adiponectin levels, and diabetes
      mellitus are associated with poor platelet responsiveness to in vitro effect of
      aspirin.
AB  - INTRODUCTION: Aspirin is one of the most effective antiplatelet agents and is now
      commonly used to prevent vascular events. In some patients, however, recurrent
      vascular events have been demonstrated despite aspirin therapy. Our objective was
      to characterize individuals showing poor response to in vitro effect of aspirin,
      using PFA-100. METHODS: One hundred sixty-eight healthy male subjects were
      analyzed. We assessed platelet function tests, including PFA-100, whole blood
      aggregation, and optical platelet aggregation. Also measured were hemostatic and
      other parameters including von Willebrand factor (VWF:Ag), VWF ristocetin
      cofactor activity (VWF:RCo), soluble vascular adhesion molecule-1 (sVCAM-1), high
      sensitive C-reactive protein (hs-CRP), and adiponectin. Poor responders were
      defined as having a collagen/epinephrine-induced closure time (CEPI-CT) under 250
      s with PFA-100 when incubated with 10 microM aspirin, whereas good responders
      were defined as having a CEPI-CT of more than 250 s. RESULTS AND CONCLUSIONS: PFA
      100 tests revealed that 40 subjects (24%) were poor responders (PR) and 128 (76%)
      were good responders (GR). Poor responsiveness was significantly associated with
      (1) higher basal platelet activities in PFA-100, as well as in whole blood
      aggregation and aggregometer;(2) increased level of adiponectin (8.8+/-4.1 micro
      g/mL [PR] vs 7.3+/-2.9 micro g/mL [GR], p=0.010);and (3) the presence of diabetes
      mellitus (17.5% [PR] vs 4.7% [GR], p=0.009). Importantly, whereas 24% of the
      subjects showed insufficient inhibition in PFA-100 when incubated with 10 microM
      aspirin, almost all subjects showed maximum inhibition with 30 microM aspirin.
      These observations suggest that higher doses of aspirin might overcome aspirin
      resistance.

PMID- 16793120
TI  - The effect of uremia on platelet contractile force, clot elastic modulus and
      bleeding time in hemodialysis patients.
AB  - INTRODUCTION: Uremic bleeding frequently occurs in dialysis patients. Although
      its mechanism is not well characterized, acquired platelet dysfunction has been
      implicated in its pathogenesis. Skin bleeding time has been used to characterize
      platelet dysfunction in this population. However, the bleeding time is prone to
      error. The goal of this study was to compare the bleeding time to the novel
      platelet function parameters platelet contractile force and clot elastic modulus
      as well as platelet aggregation studies in controls and patients receiving
      maintenance hemodialysis. MATERIALS AND METHODS: Forty-five subjects completed
      this study (25 controls, 20 dialysis). All subjects had the Ivy skin bleeding
      time procedure performed, as well as the collection of whole blood samples for
      the determination of platelet contractile force, clot elastic modulus, % von
      Willebrand Factor antigen, and platelet aggregation studies. Pearson's
      correlation determined the relationships between skin bleeding time and platelet
      function and clot structure parameters and markers of renal dysfunction. RESULTS:
      Bleeding time was significantly prolonged in the dialysis group relative to
      controls. The platelet function parameters were not significantly different
      between groups. There was a significant relationship between bleeding time and
      creatinine concentration, however, no relationship existed between bleeding time
      and platelet function parameters. CONCLUSIONS: Skin bleeding time poorly
      correlates with measurements of platelet function. There were no significant
      differences noted in platelet function between the groups despite the
      prolongations in bleeding time in the dialysis group. These data may suggest that
      the bleeding time reflects perturbations in platelet adhesion or secretion, and
      not aggregation. Further study is needed to characterize platelet function in
      dialysis patients.

PMID- 16793121
TI  - Prevalence of aspirin resistance in patients with an evolving acute myocardial
      infarction.
AB  - OBJECTIVE: To study the prevalence and importance of aspirin resistance in
      patients with an evolving acute myocardial infarction (AMI) by use of the
      Platelet Function Analyzer-100. INTRODUCTION: Previous studies have demonstrated
      the existence of aspirin resistance, but the clinical relevance of the phenomenon
      remains to be clarified. If aspirin resistant patients comprise a high-risk
      subgroup, it might be expected that the prevalence of aspirin resistance in
      patients with AMI would be higher than in patients without AMI. We hypothesized
      that the prevalence of aspirin resistance in patients with AMI was twice the
      prevalence in patients without AMI. METHODS: We included 298 consecutive patients
      with known cardiovascular disease who were admitted to hospital with symptoms
      suggestive of an AMI. All had been taking aspirin 150 mg/day for at least 7 days
      prior to hospital admission. Platelet function was measured immediately at
      admission, and aspirin resistance was defined as a collagen/epinephrine Closure
      Time (CT(CEPI))<165 s. RESULTS: We found that 70 (23.5%) patients were aspirin
      resistant, and 70 (23.5%) patients ended up with the diagnosis of an AMI. The
      prevalence of aspirin resistance was significantly higher in patients with AMI as
      compared to patients without (36% versus 20%, OR 2.26, CI 95% 1.19-4.22,
      p=0.0058). The CT(CEPI) measured at admission was an independent factor
      associated with an AMI. CONCLUSIONS: Aspirin resistance is present in almost one
      fourth of patients admitted to hospital with symptoms suggestive of an AMI, and
      aspirin resistance is significantly associated with the diagnosis of a definite
      AMI.

PMID- 16793122
TI  - Effect of substrate and fibrin polymerization inhibitor on determination of
      plasma thrombin generation in vitro.
AB  - BACKGROUND: Thrombin generation potential, a critical haemostatic measure, can be
      determined by continuous detection of total thrombin or direct subsampling.
      However, differences between methods exist in area under the curve or peak
      thrombin calculated. Also, impact of anticoagulants on thrombin generation may
      vary depending on mode of analysis. OBJECTIVE: We studied the effect of
      components on thrombin generation in the presence or absence of anticoagulants.
      METHODS: The continuous method was conducted with plasma +/- fibrin(ogen) +/-
      fibrin polymerization inhibitor. Plasma contained slow-reacting TG5134 substrate
      at 37 degrees C and reaction was started with dilute thromboplastin in
      CaCl(2)/Tris buffer. Absorbance (405 nm) was recorded over time and free thrombin
      calculated from total thrombin activity. For the subsampling method, similar
      plasma mixtures +/- TG5134 were reacted and free thrombin measured directly as
      the difference in activity against S2238 substrate of timed subsamples taken into
      EDTA or EDTA + antithrombin + heparin. RESULTS: Slow-reacting substrate in the
      continuous method acted as a competitor for thrombin, giving delayed but greater
      free thrombin than direct subsampling. These differences persisted to varying
      extents with all anticoagulants tested. In either method, presence of
      polymerization inhibitor increased the amount of free thrombin. Continuous method
      detection of alpha(2)macroglobulin complexes was hampered by sensitivity limits
      leading to inordinate free thrombin calculations. Especially with hirudin,
      although free thrombin remained at the end of the subsampling method, continuous
      method calculations assumed no residual free thrombin. CONCLUSION: In vitro
      plasma thrombin generation is delayed and increased by slow-acting substrate and
      fibrin polymerization inhibitor.

PMID- 16793123
TI  - Increased venous versus arterial thrombosis in the Factor V Leiden mouse.
AB  - BACKGROUND: Deep vein thrombosis (DVT) occurs with high prevalence in association
      with the Factor V Leiden (R506Q) mutation, whereas most evidence suggests no
      correlation with clinical arterial thrombosis. OBJECTIVE: This study compared
      arterial to venous thrombosis in the mutationally analogous Factor V Leiden
      mouse. METHODS: Three separate vascular thrombosis models were evaluated in
      Fv(+/+) (wild-type), Fv(Q/+) (heterozygous) and Fv(Q/Q) (homozygous) Factor V
      Leiden mice. RESULTS: In a FeCl(3)-induced arterial thrombosis model, no
      statistical differences among the three genotypes were found in the time to
      thrombotic occlusion. In contrast, Fv(Q/+) and Fv(Q/Q) mice demonstrated larger
      femoral vein thrombi at 30 and 60 min compared to wild-types, with Fv(Q/Q) mice
      having statistically larger thrombi than both wild-type and Fv(Q/+) mice at 10
      and 60 min and 24 h (p<0.05). In a model of thrombotic occlusion following
      arterial and venous anastomotic repair, both Fv(Q/+) and Fv(Q/Q) mice had higher
      rates of venous thrombosis than wild-types, but only Fv(Q/Q) homozygotes showed a
      statistically greater arterial occlusion rate than wild-types. CONCLUSION: The
      Factor V Leiden mouse demonstrated a greater propensity for venous vs. arterial
      thrombosis, paralleling clinical epidemiologic findings and supporting its use
      for research on deep vein thrombosis.

PMID- 16793124
TI  - Long-term outcomes following conservative surgery for borderline tumor of the
      ovary: a large population-based study.
AB  - OBJECTIVES: To examine outcomes in women treated with conservative surgery for
      borderline ovarian tumor in a large population-based cohort with long-term follow
      up. METHODS: Women treated by conservative surgery for borderline tumor of the
      ovary from 1982-2004 within a large HMO setting were identified using electronic
      and tumor registry data. Chart review was performed when electronic data were
      incomplete. The indications for and outcomes from any subsequent gynecologic
      surgery and the risk of recurrent ovarian borderline and malignant tumor were
      determined. Risk factors for recurrence were analyzed using multivariate
      regression. RESULTS: Among one hundred and ninety-three patients identified, the
      average age was 33 (12-95), with 97% having apparent Stage I disease. Patients
      were followed with remaining ovarian tissue in situ for a mean of 6.9 years, with
      59 women having 10 or more years of such observation. There were 21 recurrences
      with borderline tumor (11%) with a median time to first recurrence of 4.7 years;
      women treated by cystectomy recurred three times more often compared to women
      treated by oophorectomy (23% versus 7%). Two patients (1%) recurred with
      malignant disease involving remaining ovarian tissue, both within the first 3
      years after surgery, with one death due to recurrence. During long-term follow
      up, 19% of patients eventually underwent complete removal of ovarian tissue: in
      8%, the surgery was prophylactic, in 5%, surgery was done for benign pathology,
      and in 6% for recurrent disease. CONCLUSIONS: In this population-based HMO
      setting, 11% of women treated with conservative surgery for borderline tumor
      recurred; however, half of these recurrences were successfully managed by repeat
      conservative surgery, with only 6% of women overall needing eventual complete
      removal of ovaries for recurrent disease. Patients treated by cystectomy were
      three times more likely to recur than those treated by oophorectomy. Malignant
      recurrences were rare, and while borderline recurrences often occurred more than
      3 years after initial surgery, late malignant recurrences were not observed.
      These favorable long-term outcomes provide support for conservative surgery for
      these women.

PMID- 16793125
TI  - Adenocarcinoma of the urinary bladder presenting as locally advanced endometrial
      carcinoma. Case report and review of the literature.
AB  - BACKGROUND: Carcinoma of the urinary bladder that occurs after urinary diversion
      is a rare entity. We report a case of an adenocarcinoma arising in a
      defunctionalized bladder that presented as locally advanced endometrial
      carcinoma. CASE: A 77-year-old presented with postmenopausal bleeding and mucous
      vaginal discharge. She had a prior history of urinary diversion via a Koch pouch.
      Examination revealed a mass protruding through the cervix and possibly involving
      the bladder anteriorly. The patient underwent anterior pelvic exenteration for a
      locally advanced mucinous carcinoma thought to be arising from the uterus and
      invading into the bladder. Final pathology, however, was consistent with a
      primary bladder carcinoma. CONCLUSION: Carcinoma developing in the bladder after
      urinary diversion presents at an advanced stage and has associated poor overall
      survival.

PMID- 16793126
TI  - The effect of adjuvant chemotherapy versus whole abdominopelvic radiation on the
      survival of patients with advanced stage uterine papillary serous carcinoma.
AB  - OBJECTIVES: To compare the outcomes of stage III and IV uterine papillary serous
      carcinoma (UPSC) patients treated with platinum-based chemotherapy (PC) versus
      whole abdominopelvic irradiation (WAPI) after optimal cytoreductive surgery.
      METHODS: Surgically staged patients with advanced stage UPSC diagnosed between
      1981 and 2002 were identified from tumor registry databases at four hospitals.
      Survival analyses and predictors of outcome were analyzed using Kaplan-Meier
      methods. RESULTS: Of the 40 patients with advanced UPSC (median age: 64.5), 84%
      were Caucasian, 8% were African American, and 8% were Asian. The majority of
      patients (85%) presented with vaginal bleeding. Twenty-seven had stage III and 13
      had stage IV disease. All patients were optimally debulked; 21 patients received
      adjuvant PC while 19 underwent WAPI. The median follow-up was 27 months (range: 5
      209). The 3-year overall survival (OS) and progression-free survival (PFS) for
      the patients with stage III disease were 49% and 37% compared to 37% and 31% in
      those with stage IV disease (P = 0.23 for OS; P = 0.41 for PFS). Women who
      received PC had a 3-year OS and PFS of 43% and 31% compared to 45% and 41% in
      those receiving WAPI, respectively (P = 0.40 for OS; P = 0.84 for PFS).
      CONCLUSION: Platinum-based chemotherapy or whole abdominopelvic irradiation
      resulted in similar survival in this series of women with optimally cytoreduced
      UPSC. Given the overall poor prognosis of these patients, new treatment
      modalities are warranted.

PMID- 16793127
TI  - PTEN mutation, expression and LOH at its locus in ovarian carcinomas. Relation to
      TP53, K-RAS and BRCA1 mutations.
AB  - OBJECTIVE: We aimed to evaluate frequency of PTEN mutation, LOH and expression in
      ovarian tumors. In search for a molecular pathway, we confronted PTEN gene
      mutations with TP53, K-RAS and BRCA1 gene status in the same tumors. We also
      evaluated clinical significance of PTEN expression in a subgroup of patients
      uniformly treated with platinum-based regimens. METHODS: Molecular analysis was
      performed on 105 ovarian tumors (100 carcinomas) with the use of the SSCP and
      sequencing. Seventy-six tumors were analyzed for LOH at 10q23 locus with the use
      of six polymorphic markers. Immunohistochemical PTEN expression was done on
      paraffin-embedded material. Multivariate and univariate analysis was performed
      with the STATA program. RESULTS: PTEN mutations occurred in 5/100 (5%) of all
      carcinomas and in 3/15 (20%) of endometrioid carcinomas (EC). Low-grade EC that
      developed in borderline tumors had PTEN and/or K-RAS mutation (4/5, 80%), while
      high-grade EC had TP53 mutations only. There was a reverse association between
      PTEN and TP53 mutations (P = 0.005). LOH at PTEN locus was found in 60% of
      endometrioid and in 28% of serous and clear cell carcinomas. PTEN expression did
      not associate with PTEN mutations or LOH. Strong PTEN expression diminished risk
      of death in a TP53 positive group only (HR = 0.35, P = 0.029). CONCLUSION: Our
      results suggest that PTEN mutations may play a role in a development of low-grade
      endometrioid tumors. PTEN haploinsufficiency caused by LOH or epigenetic events
      may possibly contribute to development of other histological types and may be an
      adverse prognostic factor.

PMID- 16793128
TI  - Photodynamic therapy using a methyl ester of 5-aminolevulinic acid in recurrent
      Paget's disease of the vulva: a pilot study.
AB  - OBJECTIVE: In the past, treating vulvar Paget's disease through surgery has
      resulted in a high recurrence rate of the disease. Photodynamic therapy (PDT)
      using 5-aminolevulinic acid (5 ALA) is an effective treatment for some conditions
      such as Bowen's disease, subsets of basal cell carcinomas and vulvar carcinoma.
      Methyl 5-aminolevulinate (MAL) is an ester of 5 ALA that seems to be more
      effective and produces fewer side effects than 5 ALA. This paper outlines a pilot
      study designed to test the feasibility of using MAL-PDT in the treatment of
      recurrent vulvar Paget's disease. METHODS: 5 MAL-PDT was applied for 3 h and than
      irradiated with red-light (620 nm) using a total light dose of 37 J/cm2 for a
      period of 10 min. Patients taking part in the study were treated once every 3
      weeks, for a total of three treatments. Vulvar biopsies were obtained before and
      1 month after the PDT-treatment. RESULTS: Seven patients were enrolled in the
      study. Four cases had a complete clinical response, and this was pathologically
      confirmed in two of the cases. The cosmetic outcome was acceptable and the
      treatment was well tolerated. All the patients developed local edema and mild
      local pain, controlled with non-steroidal antiinflammatory drugs (NSAIDS). One
      patient experienced severe pain and a mild local phototoxicity reaction.
      CONCLUSIONS: MAL-PDT is a feasible treatment and seems to offer a reliable
      strategy in the control of vulvar Paget's disease and of its symptoms.

PMID- 16793129
TI  - Estrus variation in anticonflict-like effects of the mGlu5 receptor antagonist
      MTEP, microinjected into lateral septal nuclei of female Wistar rats.
AB  - Anticonflict-like effects of the mGlu5 receptor antagonist MTEP (systemic
      administrations: 1.50, 3.0 or 6.0 mg/kg; i.p.; intra-lateral septal nuclei or
      intra-medial septal region infusions: 2.5 microg/microl, 5.0 microg/microl or
      10.0 microg/microl) were assessed in Wistar rats during late proestrus or
      metestrus-diestrus. Results showed that control rats displayed an increased
      number of immediately punished reinforcers during late proestrus (P < 0.05), when
      compared to metestrus-diestrus. During late proestrus, systemic administrations
      (3.0 mg/kg, P < 0.05; 6.0 mg/kg P < 0.05) or intra-lateral septal nuclei
      infusions (5.0 microg/microl, P < 0.05; 10.0 microg/microl, P < 0.05) of MTEP
      increased the number of immediately punished reinforcers received. During
      metestrus-diestrus only the highest doses of MTEP (systemic administration: 6.0
      mg/kg P < 0.05; intra-lateral septal nuclei infusions: 10.0 microg/microl, P <
      0.05) increased the number of immediately punished reinforcers obtained. MTEP
      infusions into the medial septum produced neither of these anticonflict effects.
      In conclusion, data showed an estrus variation in those anticonflict-like effects
      of the mGlu5 receptor antagonist MTEP, systemically administered or microinjected
      into lateral septal nuclei of female Wistar rats.

PMID- 16793130
TI  - Cross-language lexical connections in the mental lexicon: evidence from a case of
      trilingual aphasia.
AB  - Despite anecdotal data on lexical interference among the languages of
      multilingual speakers, little research evidence about the lexical connections
      among multilinguals' languages exists to date. In the present paper, two
      experiments with a multilingual speaker who had suffered aphasia are reported.
      The first experiment provides data about inter-language activation during natural
      conversations; the second experiment examines performance on a word-translation
      task. Asymmetric patterns of inter-language interference and translation are
      evident. These patterns are influenced by age of language learning, degree of
      language recovery and use, and prevalence of shared lexical items. We conclude
      that whereas age of language learning plays a role in language recovery following
      aphasia, the degrees of language use prior to the aphasia onset and of shared
      vocabulary determine the ease with which words are accessed. The findings
      emphasize the importance of patterns of language use and the relations between
      the language pair under investigation in understanding lexical connections among
      languages in bilinguals and multilinguals.

PMID- 16793131
TI  - Differential inflammatory macrophage response to rutile and titanium particles.
AB  - Titanium and its alloys are widely used as implant materials for dental and
      orthopaedic applications due to their advantageous bulk mechanical properties and
      biocompatibility, compared to other metallic biomaterials. In order to improve
      their wear and corrosion resistance, several surface modifications that give rise
      to an outer ceramic layer of rutile have been developed. The ability of rutile
      wear debris to stimulate the release of inflammatory cytokines from macrophages
      has not been addressed to date. We have compared the in vitro biocompatibility of
      sub-cytotoxic doses of rutile and titanium particles in THP-1 cells driven to the
      monocyte/macrophage differentiation pathway as well as in primary cultures of
      human macrophages. Confocal microscopy experiments indicated that differentiated
      THP-1 cells and primary macrophages efficiently internalised rutile and titanium
      particles. Treatment of THP-1 cells with rutile particles stimulated the release
      of TNF-alpha, IL-6 and IL-1beta to a lesser extent than titanium. The influence
      of osteoblasts on the particle-induced stimulation of TNF-alpha and IL-1beta was
      analysed by co-culturing differentiated THP-1 cells with human primary
      osteoblasts. Under these conditions, secretion levels of both cytokines after
      treatment of THP-1 cells with rutile particles were lower than after exposure to
      titanium. Finally, we observed that primary macrophages released higher amounts
      of TNF-alpha, IL-6 and IL-1beta after incubation with titanium particles than
      with rutile. Taken together, these data indicate that rutile particles are less
      bioreactive than titanium particles and, therefore, a higher biocompatibility of
      titanium-based implants modified with an outer surface layer of rutile is
      expected.

PMID- 16793132
TI  - Synthesis of cell-adhesive dextran hydrogels and macroporous scaffolds.
AB  - Dextran hydrogels have been previously investigated as drug delivery vehicles and
      more recently as macroporous scaffolds; however, the non-cell-adhesive nature of
      dextran has limited its utility for tissue engineering. To overcome this
      limitation, macroporous scaffolds of methacrylated dextran (Dex-MA) copolymerized
      with aminoethyl methacrylate (AEMA) were synthesized, thereby introducing primary
      amine groups for covalent immobilization of extracellular-matrix-derived
      peptides. The amino group density for hydrogels copolymerized with 0.5 wt% AEMA
      was found to be 36.1+/-0.4 micromol/cm(3) by elemental analysis. To further
      enhance cellular interaction, poly(Dex-MA-co-AEMA) hydrogels were modified with
      either CRGDS or a mixture of CDPGYIGSR and CQAASIKVAV (1:1, v/v) using sulfo-(N
      maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC). The immobilized peptide
      concentration was determined using amino acid analysis at: 2.6+/-0.9
      micromol/cm(3) for CRGDS-derived hydrogels and 2.2+/-0.3 micromol/cm(3) plus
      1.9+/-0.2 micromol/cm(3) for CDPGYIGSR plus CQAASIKVAV-derived hydrogels,
      respectively. Cellular interactions of primary embryonic chick dorsal root
      ganglia (DRGs) were compared on the hydrogels. Cell adhesion and neurite
      outgrowth on poly(Dex-MA) increased with copolymerization of AEMA and further
      improved with peptide modification and significantly for CDPGYIGSR/CQAASIKVAV
      derived poly(Dex-MA-co-AEMA) hydrogels. Moreover, DRGs penetrated within the
      first 600 microm of the scaffolds, thereby demonstrating the potential of this
      scaffold for guided cell and axonal regeneration in vivo.

PMID- 16793133
TI  - Post-Translational Modifications of the P2X(4) purinergic receptor subtype in the
      human placenta are altered in preeclampsia.
AB  - P2X(4) receptors are activated by extracellular ATP to raise intracellular
      calcium, thus altering cell signalling. ATP release occurs under
      pathophysiological, stress and adverse cell conditions; these are all increased
      in preeclampsia. Although P2X(4) is abundantly expressed in normal placenta
      neither the differences in the amount of protein nor its post-translational
      modifications have been studied in placentae from pregnancies complicated by
      preeclampsia. Thus we examined P2X(4) protein expression, localization and post
      translational modifications in normotensive controls, term and preterm
      preeclamptic placentae. Densitometric analysis of Western blots showed a
      significant increase in P2X(4) protein expression in both term (p=0.002) and
      preterm preeclamptic (p=0.0008) placental samples compared to normotensive
      controls however the tissue localization of this receptor subtype was unaltered
      across the groups. Our data showed that P2X(4) is a nitrated protein in the
      placenta and this nitration is upregulated in preterm preeclamptic placenta
      compared to normotensive controls (p=0.03). We also demonstrated that P2X(4) is
      heavily glycosylated in the placenta by deglycosylation with PNGase F which
      reduced the protein product size by 23 kDa. We propose that P2X(4) acts within
      the syncytiotrophoblast to alter intracellular calcium and subsequent signalling
      pathways thereby restoring placental cell homeostasis following ATP-induced
      changes during pathophysiological conditions such as preeclampsia. We also
      propose that the post-translational modifications of nitration and glycosylation
      are required for the normal functioning of P2X(4).

PMID- 16793134
TI  - First evidence of the activation of Cg-timp, an immune response component of
      Pacific oysters, through a damage-associated molecular pattern pathway.
AB  - In a previous work, we characterized a Crassostrea gigas cDNA (Cg-timp) encoding
      a protein which presents all the features of vertebrate tissue inhibitor of
      metalloproteinase (TIMP). The expression pattern of this gene led us to propose
      that Cg-timp is an important factor in oyster wound healing and defense
      mechanisms. Here we describe the analysis of Cg-timp expression in oysters
      challenged by live or dead bacteria as well as by bacterial secretory/excretory
      products and metalloproteinase. Surprisingly, bacterial secretory/excretory
      products activate Cg-timp gene expression whereas heat-inactivated ones do not.
      To address the question of the signal transduction pathway involved in Cg-timp
      gene activation, we isolated and sequenced Cg-timp promoter and upstream region.
      A 1-kb genomic DNA fragment flanking the 5'-end of the gene contains several
      regulatory elements and notably three NF-kappaB binding sites. The potential
      involvement of these motifs in Cg-timp gene regulation is discussed.

PMID- 16793135
TI  - Ameliorative effect of melatonin against gamma-irradiation-induced oxidative
      stress and tissue injury.
AB  - While radiation hazards, due to free radical generation, present an enormous
      challenge for biological and medical safety, melatonin is a potent scavenger of a
      variety of free radicals. The aim of this study was to investigate the
      radioprotective effect of melatonin against oxidative stress and tissue injury
      induced by gamma radiation. Rats were subjected to two doses of 2 and 4Gy from
      cesium-137 source. Four days prior to irradiation, animals received melatonin
      daily (10mg/kg body weight i.p.). In the irradiated animals, the oxidative stress
      markers malondialdehyde (MDA) and protein carbonyl were significantly increased
      in the liver, while a marked decrease in hepatic contents of DNA, RNA, and
      glutathione (GSH) as well as activity of glutathione-S-transferase (GST) was
      demonstrated. In addition, catalase (CAT) activity was increased in the liver 5
      days after irradiation. The levels of total lipids, cholesterol, triglyceride
      (TG), low-density lipoprotein (LDL), urea, and creatinine, as well as activities
      of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma
      glutamyltransferase (GGT), were significantly increased in sera of the irradiated
      rats. This is coupled with decreased serum levels of high-density lipoprotein
      (HDL), total protein and albumin, and total globulins by irradiation. The
      administration of melatonin alone daily for 4 days caused significant decreases
      in MDA and protein carbonyl content and produced significant elevations of GSH
      content and GST activity in the liver. Moreover, significant decreases in total
      lipids, cholesterol, and TG without change in LDL or HDL levels in serum were
      demonstrated. Treatment with melatonin for 4 days before acute irradiation
      significantly abolished radiation-induced elevations in MDA and protein carbonyl
      levels in the liver and significantly maintained hepatic GSH content, GST, and
      CAT activities close to the control values. Preirradiation treatment with
      melatonin showed significantly higher hepatic DNA and RNA contents than
      irradiated rats. The levels of total lipids, cholesterol, TG, HDL, LDL, total
      proteins, albumin, total globulins, creatinine, and urea, as well as the
      activities of AST, ALT, and GGT in serum were significantly ameliorated when
      melatonin was injected before irradiation. In conclusion, the increase in
      oxidative stress markers and the concomitant change in antioxidant levels
      indicate the role of oxidative stress in radiation-induced tissue damage.
      Moreover, melatonin shows a radioprotective impact against ionizing-radiation
      induced oxidative stress and organ injury.

PMID- 16793136
TI  - Intellectual disability and mental illness in the NSW criminal justice system.
AB  - There has been increasing international, national and local recognition of the
      need for more appropriate responses and services for individuals who come in
      contact with the criminal justice system and who have an intellectual disability
      and mental health issues. This article provides an overview of prevalence data
      that indicates a significant over representation of people with intellectual
      disabilities in correctional facilities and reviews the problems facing this
      population. Findings from two specific evaluation studies undertaken by the
      Centre for Developmental Disability Studies are presented, along with
      recommendations for future provision based on these results. One of these
      projects trialled a case management approach to supporting offenders with an
      intellectual disability upon their release from prison. The 20-month follow-up
      found that a number of serious barriers were encountered within the overall
      system of provision for this population; the most serious of which related to
      lack of adequate accommodation upon release. The second project involved a two
      stage evaluation of one model of provision for individuals with intellectual
      disabilities who are sex offenders, only some of whom were on parole. This
      service provided both residential and therapy services in a small group home
      located in the community. Residents were found to have high levels of emotional
      and behavioural difficulties, in addition to offending behaviour, that continue
      to require support and supervision. Critical issues, including guardianship
      involvement, restrictive practices and retrieval, therapy provision, and risk
      management issues are discussed in relation to overall clinical and lifestyle
      outcomes.

PMID- 16793137
TI  - Prevalence of mental disorders among sexual offenders in forensic psychiatry and
      prison.
AB  - The objective of this study was to compare the prevalence of mental disorders
      among sexual offenders in forensic psychiatry (SF) with the prevalence of such
      disorders among sexual offenders in prison (SP) and violent offenders in prison
      (VP). In a cross-sectional study, 40 of 47 SF detained in forensic psychiatry in
      Baden-Wuerttemberg, Germany, could be included. They were compared with 30 SP and
      26 VP. All study participants were interviewed by means of SCID I and SCID II and
      assessments of functioning (GAF, BSS). There was a high prevalence of mental
      disorders (DSM-IV: Axis I) in all three groups (SF: 80%, SP: 63%, VP: 73%). Among
      SP and VP, this was attributed mainly to substance use disorders. The prevalence
      and comorbidity of personality disorders was significantly higher in the group of
      the SF (prevalence: SF: 85%, SP: 27%, VP: 39%). In a psychopathological view, SP
      were all together more similar to the imprisoned non-sexual delinquent VP than to
      the SF.

PMID- 16793138
TI  - Characterization of human monoclonal autoantibody Fab fragments against oxidized
      LDL.
AB  - Oxidized low-density lipoprotein (oxLDL) is a key autoantigen in atherosclerosis.
      The genetic structures and pathogenic roles of autoantibodies against this
      protein remain to be established. In this study, we cloned several monoclonal IgG
      autoantibody Fab fragments specific for oxLDL from peripheral blood lymphocytes
      of atherosclerosis patients, using phage display technology. The sequences of
      their variable regions were determined at the cDNA level. The closest germline
      counterparts for the heavy chains belonged to the V(H)3 or V(H)1 family. The
      sequences and lengths of complementarity-determining regions (CDR)3-V(H) were
      diverse, and frequent mutations of positively charged amino acids (particularly
      arginine) over entire V(H) and V(L) sequences were observed. It is proposed that
      anti-oxLDL autoantibody formation is driven by antigens. Among the Fabs, P2-8 and
      P3-175 bound to both MDA-LDL and Cu-oxLDL, and inhibited the uptake of oxLDL by
      macrophages, suggesting the epitope(s) recognized by the Fabs is a part of
      ligands on oxLDL that is involved in uptake by macrophage scavenger receptor.
      These human autoantibody Fabs require detailed investigation to ascertain their
      potential as agents for clinical applications.

PMID- 16793139
TI  - A new mechanism for generating TCR diversity: A TCR Jalpha-like gene that inserts
      partial nucleotide sequences in a D-gene manner.
AB  - delta-TCR genes of two gammadelta-T cell hybridomas were found to contain an
      identical 19-nt sequence in their non-germline N-regions. To determine if this
      sequence represented a third murine TCR Ddelta gene, genomic PCR was performed by
      using it as a primer together with primers for interspersed repetitive elements
      (IRE). Sequencing revealed that the 19-nt segment is part of a 61-nt gene with
      flanking 5' and 3' recombination signaling sequences (RSS). Southern blot
      analysis confirmed the presence of this 61-nt gene in the genome of several mouse
      strains. The gene is unusual in that the distal 24 nucleotides of its 3' RSS
      region are contributed by the 5' portion of a B2 IRE sequence that includes an
      apparently non-functional RNA splice site within the 3' nonamer sequence. It has
      sequence similarities with the Ddelta1 gene (81%) at its 5' end and with Jalpha
      genes (73%) overall. Tyramide-FISH analysis identified the gene to exist within
      or adjacent to the TCR alpha/delta locus on chromosome 14. Surveys of available
      TCR sequences reveal possible partial insertions of the 61-nt gene in other delta
      TCR and in alpha-TCR gene sequences. Thus, the unique 61-nt gene is Jalpha gene
      like in structure but D gene-like in function.

PMID- 16793140
TI  - Treatment adequacy of anxiety and depressive disorders: primary versus
      specialised care in Spain.
AB  - BACKGROUND: Literature suggests that a high proportion of the population with
      mental disorders remains either untreated or poorly treated. This study aimed to
      describe the adequacy of treatment for Anxiety and Depressive disorders in Spain,
      how this differs between providers (primary versus specialised care) and which
      factors are associated with appropriate care. METHOD: Data were derived from the
      Spanish sample (N=5473) of the European Study of the Epidemiology of Mental
      Disorders (ESEMeD), a cross sectional study in a representative sample of adults.
      The subsample analyzed was composed by the 133 subjects with a mental disorder in
      the year prior to the interview who received treatment. Treatment adequacy was
      evaluated in two different ways: (1) considering definitions of minimally
      adequate treatment evidence based guidelines and criteria used in other
      epidemiological studies; (2) considering experts rating of treatment
      appropriateness based on the information contained in the case vignettes created
      from the CIDI answers. Generalised Estimating Equation (GEE) models and simple
      logistic regression were conducted to assess the correlates of adequate
      treatment. RESULTS: Similar proportions of patients in specialty and general
      medical treatment received a minimally adequate treatment (31.8% and 30.5%,
      respectively). Associated factors to appropriateness were living in a large city,
      having a high educational level, and having a good self rated health state.
      LIMITATIONS: Treatment adequacy was based on simple information and criteria.
      CONCLUSIONS: Only one third of the mental health treatment in Spain met minimal
      adequacy criteria. More research is needed in order to find out reasons for these
      low rates.

PMID- 16793141
TI  - Sex differences in the familial transmission of mood disorders.
AB  - BACKGROUND: Mood disorders exhibit familial transmission due to both
      environmental and genetic risk factors. Mood disorders are more common in women,
      yet the role of gender in the familial transmission of mood disorders is unclear.
      This study examines rates of mood disorder transmission to offspring based on the
      sex of affected parent, sex of offspring and role of clinical factors, such as
      childhood abuse history, comorbid psychiatric disorders, and traits of aggression
      and impulsivity. METHODS: Risk of transmission of mood disorder to offspring from
      females and males was compared in a sample of 272 probands with a major mood
      disorder using generalized estimating equations (GEE). Demographic and clinical
      characteristics of all male and female probands were compared. Characteristics
      that differed in probands were entered into the model to obtain an unbiased test
      of gender differences in transmission rate. Multivariate GEE models, one for male
      probands and one for female probands, were used to test for risk factors in
      transmission of mood disorder. RESULTS: Familial transmission rate of mood
      disorders from female probands was almost double that of males. There was no
      difference in transmission to male or female offspring. For male probands,
      offspring mood disorder was independently associated with earlier age of proband
      mood disorder onset, greater number of proband years ill, and proband history of
      childhood abuse. For female probands, offspring mood disorder was associated with
      higher aggression scores in probands. LIMITATIONS: We did not directly interview
      offspring and also had limited data on psychopathology in co-parents. This is a
      cross-sectional study and cannot account for emergence of illness in offspring in
      the future. CONCLUSIONS: The two-fold higher rate of maternal transmission of
      mood disorder may reflect differences in regulation of maternal and paternal
      transmission of mood disorder. Future studies need to determine the relative
      contribution of genetic and non-genetic factors and identify the factors
      responsible for higher rates of transmission of mood disorders by females with a
      mood disorder.

PMID- 16793142
TI  - Cannabis use and expression of mania in the general population.
AB  - BACKGROUND: Cannabis use is common in patients with bipolar disorder, however
      little is known about cannabis as a risk factor for mania. In order to
      investigate the association between exposure to cannabis and subsequent
      development of manic symptoms whilst controlling for psychotic symptoms, a
      longitudinal population-based study was carried out. METHODS: 4815 individuals
      aged 18 to 64 years were interviewed using the Composite International Diagnostic
      Interview at baseline, 1 year follow up and 3 year follow up, including
      assessment of substance use, manic symptoms and psychotic symptoms. RESULTS: Use
      of cannabis at baseline increased the risk for manic symptoms during follow-up
      (adjusted OR 2.70, 95% CI: 1.54, 4.75), adjusted for age, sex, educational level,
      ethnicity, single marital status, neuroticism, use of other drugs, use of
      alcohol, depressive symptoms and manic symptoms at baseline. The association
      between cannabis use and mania was independent of the prevalence and the
      incidence of psychotic symptoms. There was no evidence for reverse causality, as
      manic symptoms at baseline did not predict the onset of cannabis use during
      follow-up (OR = 0.35, 95% CI: 0.03, 3.49). LIMITATIONS: As 3 years is a relative
      short period of follow-up, long-term effects of cannabis use on mania outcomes
      could not be detected. CONCLUSION: The results suggest that cannabis use may
      affect population expression of manic symptoms (and subsequent risk to develop
      bipolar disorder [Regeer, E.J., Krabbendam, L., R, DE Graaf, Ten Have, M., Nolen,
      W.A., Van Os, J., 2006. A prospective study of the transition rates of
      subthreshold (hypo)mania and depression in the general population. Psychol Med, 1
      9.]). These findings may not be due to the emergence of psychotic symptoms or the
      effects of self-medication.

PMID- 16793143
TI  - Differential performance on tasks of affective processing and decision-making in
      patients with Panic Disorder and Panic Disorder with comorbid Major Depressive
      Disorder.
AB  - BACKGROUND: Neuropsychological studies have provided evidence for deficits in
      psychiatric disorders, such as schizophrenia and mood disorders. However,
      neuropsychological function in Panic Disorder (PD) or PD with a comorbid
      diagnosis of Major Depressive Disorder (MDD) has not been comprehensively
      studied. The present study investigated neuropsychological functioning in
      patients with PD and PD + MDD by focusing on tasks that assess attention,
      psychomotor speed, executive function, decision-making, and affective processing.
      METHODS: Twenty-two unmedicated patients with PD, eleven of whom had a secondary
      diagnosis of MDD, were compared to twenty-two healthy controls, matched for
      gender, age, and intelligence on tasks of attention, memory, psychomotor speed,
      executive function, decision-making, and affective processing from the Cambridge
      Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and
      Affective Go/No-go Task. RESULTS: Relative to matched healthy controls, patients
      with PD + MDD displayed an attentional bias toward negatively-valenced verbal
      stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge
      Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of
      memory and visual discrimination compared to their controls. In contrast, no
      group differences were found for PD patients relative to matched control
      subjects. LIMITATIONS: The sample size was limited, however, all patients were
      drug-free at the time of testing. CONCLUSIONS: The PD + MDD patients demonstrated
      deficits on a task involving visual discrimination and working memory, and an
      attentional bias towards negatively-valenced stimuli. In addition, patients with
      comorbid depression provided qualitatively different responses in the areas of
      affective and decision-making processes.

PMID- 16793144
TI  - Contrast sensitivity in seasonal and nonseasonal depression.
AB  - BACKGROUND: Psychophysics has been used for the early diagnosis of many diseases
      that affect the visual pathway including those not usually considered vision
      related (e.g., Parkinson's disease). Little has been done, however, to
      investigate visual functioning in psychological disorders known to be effectively
      treated by phototherapy. We measured the static and dynamic spatial contrast
      detection thresholds of seasonally depressed (SAD), nonseasonally depressed
      (Depressed) and nondepressed (Control) individuals. METHODS: Two psychophysical
      experiments which measured luminance contrast detection thresholds were
      conducted. Experiment 1 presented static, vertically oriented Gabors with center
      spatial frequencies ranging from 0.3 to 12.0 cpd (cycles per degree). Experiment
      2 presented 0.5, 1.5 and 4.0 cpd Gabors whose phases were sinusoidally reversed
      at 2.0, 4.0, 8.0, 16.0, and 32.0 c/s (Hz). RESULTS: SAD showed significantly
      greater contrast sensitivities than Controls for static spatial frequencies equal
      to or greater than 6.0 cpd. Depressed showed significantly greater contrast
      sensitivities at 6.0 cpd and 12.0 cpd. With phase modulation, the SAD group
      showed significantly enhanced contrast sensitivity with 4.0 cpd-2.0 Hz Gabors.
      All other results at lower spatial-higher temporal frequencies were not
      significant. LIMITATIONS: Most of the subjects were drawn from the student
      population instead of the community or clinics, even though they met the criteria
      for clinical depression. Antidepressant use was not controlled for among the
      subjects. CONCLUSIONS: These findings suggest that clinical depression can
      enhance contrast sensitivity when stimuli elicit strong parvocellular responses.
      These enhancements implicate differences in retinal functionality. Mechanisms
      that link neuromodulatory activity to retinal signal processing are proposed.

PMID- 16793145
TI  - Adenoviral delivery of IL-1 receptor antagonist abrogates disease activity during
      the development of autoimmune arthritis in IL-1 receptor antagonist-deficient
      mice.
AB  - Currently available treatments for rheumatoid arthritis (RA) are limited in terms
      of their long-term effects and their abilities to control disease progression.
      Interleukin-1 receptor antagonist (IL-1Ra) is a natural inhibitor of the biologic
      actions of IL-1, which is known to promote inflammation and degeneration of the
      joint. In this study, we investigated whether human IL-1Ra gene transfer is
      effective at treating an established experimental arthritis model. A recombinant
      adenovirus carrying the gene that encode human hIL-1Ra and GFP (Ad.hIL-1Ra/GFP)
      was administered by intra-articular injection into the ankle joints of the mice
      with established the IL-1Ra-deficient Balb/cA mice (IL-1Ra(-/-)), which develop
      spontaneously chronic inflammatory arthropathy. The effects of two injections of
      Ad.hIL-1Ra/GFP or control virus with no inserted target gene (Ad.GFP) were
      compared with the effects of PBS injection with respect to the clinical
      characteristics of arthritis, as determined by articular index scores,
      histopathological and immunological assays. We further divided the outcomes of
      Ad.hIL-1Ra/GFP gene therapy in IL-1Ra(-/-) mice according arthritis stage; early
      stage and chronic stage corresponding to 8 and 15 weeks of age, respectively.
      Intra-articular injections of Ad.hIL-1Ra/GFP reduced arthritis severity and
      footpad swelling compared with control groups treated with Ad.GFP or PBS in early
      stage IL-1Ra(-/-) mice. Moreover, the histopathology of the ankle joints of IL
      1Ra(-/-) mice treated with Ad.hIL-1Ra/GFP showed a significant decrease in
      synovial proliferation and inflammatory cell infiltration, and preserved
      proteoglycan levels in the joints of early stage IL-1Ra(-/-) mice compared with
      the control mice. Moreover, Ad.hIL-1Ra/GFP treated mice showed reduced levels of
      inflammatory T helper type 1 (Th1) driven IgG2a antibodies to collagen type II
      but increased levels Th2 driven IgG1 antibody. These results suggest that
      adenovirus-mediated gene transfer of IL-1Ra may be a promising therapeutic option
      in the early stage of autoimmune arthritis.

PMID- 16793146
TI  - Enhancing immune responses against HIV-1 DNA vaccine by coinoculating IL-6
      expression vector.
AB  - DNA vaccines have a demonstrated ability to induce humoral and cellular immune
      responses in animal models and humans. To analyze the immunogenicity of HIV-1 DNA
      vaccine which expressing the chimeric gene gag-gp120 of Chinese prevalent HIV-1
      strain and the immunoregulatory activity of IL-6, DNA vaccine plasmid pVAX1-gag
      gp120 and eukaryotic expression plasmid pVAX1-IL6 were constructed and the
      expression in vitro was detected by RT-PCR and Western blotting, the results
      showed that the gene of interest expressed in the transfected HeLa cells. To
      explore the immune response in mice coinoculated with HIV-1 DNA vaccine and IL-6
      expression plasmid, BALB/c mice were injected i.m. with eukaryotic expression
      plasmid pVAX1-IL6 and DNA vaccine plasmid pVAX1-gag-gp120. The specific humoral
      and cellular immunity in mice could be induced by inoculating separately HIV-1
      DNA vaccine plasmid or coinoculating with IL-6 expression plasmid, and the
      specific killing activities of spleen CTL and the level of serum antibodies in
      the coinoculation group were significantly higher than those in the separate
      inoculation group. These results strongly support the use of IL-6 as a cytokine
      adjuvant in DNA vaccination.

PMID- 16793147
TI  - The dark side of high-frequency oscillations in the developing brain.
AB  - Adult brain networks generate a wide range of oscillations. Some of these are
      behaviourally relevant, whereas others occur during seizures and other
      pathological conditions. This raises the question of how physiological
      oscillations differ from pathogenic ones. In this review, this issue is discussed
      from a developmental standpoint. Indeed, both epileptic and physiological high
      frequency oscillations (HFOs) appear progressively during maturation, and it is
      therefore possible to determine how this program corresponds to maturation of the
      neuronal populations that generate these oscillations. We review here important
      differences in the development of neuronal populations that might contribute to
      their different oscillatory properties. In particular, at an early stage, the
      density of glutamatergic synapses is too low for physiological HFOs but an
      additional drive can be provided by excitatory GABA, triggering epileptic HFOs
      and the cascades involved in long-lasting epileptogenic transformations. This
      review is part of the INMED/TINS special issue "Nature and nurture in brain
      development and neurological disorders", based on presentations at the annual
      INMED/TINS symposium (http://inmednet.com/).

PMID- 16793148
TI  - Antivirals in the transplant setting.
AB  - Over the past quarter of a century, antiviral drugs have moved from an
      experimental adventure in transplant patients to a situation where they are used
      routinely to prevent diseases caused by several viruses. Furthermore, they have
      significantly reduced several medical complications of transplantation, such as
      graft rejection, thereby implicating viruses as components of their pathogenesis.
      By controlling these major complication, the development of these antiviral drugs
      and their prodrugs, has therefore greatly facilitated the clinical expansion of
      transplantation, allowing life saving procedures to be offered to more patients
      who could potentially benefit. This article will briefly summaries which viruses
      are important following transplantation and outline the evidence-base from
      randomized controlled clinical trails for the deployment of antiviral drugs to
      prevent viral diseases.

PMID- 16793149
TI  - Temporary third-degree atrioventricular block in a case of apical ballooning
      syndrome.
AB  - Apical ballooning is characterized by severe but reversible contractile
      dysfunction. The causative factor and the pathomechanism remain unknown. Several
      arrhythmias are reported to occur in apical-ballooning. We present a unique case
      of a 58-year-old man presenting with apical ballooning complicated by a prolonged
      third-degree atrioventricular block requiring the implantation of a pacemaker.

PMID- 16793150
TI  - Abnormal endothelial function in female patients with hypothyroidism and
      borderline thyroid function.
AB  - BACKGROUND: It has been suggested that hypothyroidism is associated with an
      increased risk for cardiovascular disease. The aim of this study was to assess
      non-invasively NO-dependent endothelial function of resistance arteries in
      subjects with hypothyroidism of varying severity. METHODS: Ninety-six female
      subjects (aged: 42+/-13 years) comprised the study population. Subjects were
      divided into five groups based on TSH levels at presentation: Group 0 (n=23) with
      TSH: 0.3-2.0 microU/ml, Group 1 (n=22) with TSH: 2.1-4.0 microU/ml (upper
      normal), Group 2 (n=18) with TSH: 4.1-10 microU/ml (subclinical hypothyroidism),
      Group 3 (n=22) with TSH >10 microU/ml (overt hypothyroidism). One additional
      group with well-controlled hypothyroidism on L-thyroxine therapy (Group 4, n=11,
      TSH: 0.3-2.0 microU/ml) was also studied. Endothelial function of resistance
      arteries was assessed by measuring forearm blood flow response during reactive
      hyperemia utilizing venous occlusion strain-gauge plethysmography. RESULTS:
      Duration of reactive hyperemia was significantly different among groups of
      subjects with varying hypothyroidism (83.7+/-58.3 s, 53.2+/-35.7 s, 52.8+/-47.5
      s, 12.9+/-13.3 s and 69.5+/-26.2 s in Groups 0, 1, 2, 3 and 4, respectively,
      p<0.001, ANOVA). Duration of reactive hyperemia was significantly shorter in
      subjects with upper normal TSH values (Group 1) compared to controls (53.2+/-35.7
      s vs. 83.7+/-58.3 s, p=0.013), while it was comparable to that of subjects with
      subclinical hypothyroidism (Group 2) (52.8+/-47.5 s). However, duration of
      reactive hyperemia in Group 1 was significantly longer compared to Group 3 (overt
      hypothyroidism) (53.2+/-35.7 s vs. 12.9+/-13.3 s, p=0.002). Similarly, duration
      of reactive hyperemia in subjects with subclinical hypothyroidism was
      significantly longer compared to subjects with overt hypothyroidism (52.8+/-47.5
      s vs. 12.9+/-13.3 s, p=0.003). Duration of reactive hyperemia in Group 4 (well
      controlled hypothyroidism on L-thyroxine therapy) did not differ significantly
      compared to controls. There was a highly significant linear correlation between
      duration of reactive hyperemia and TSH (r=-0.383, p<0.001). CONCLUSION:
      Endothelial dysfunction was detected in the microvasculature of patients with
      hypothyroidism. Duration of reactive hyperemia decreased with increasing TSH
      levels. Since endothelial dysfunction is a factor leading to atherosclerosis,
      this abnormality may partly explain predisposition of patients with thyroid
      failure to cardiovascular disease.

PMID- 16793151
TI  - A potential evidence to explain the reason behind the devastating prognosis of
      coronary artery disease in uraemic patients: renal insufficiency is associated
      with poor coronary collateral vessel development.
AB  - The potential of individuals to develop coronary collateral circulation is often
      neglected but is of potential major importance in myocardial vulnerability.
      Likewise, the effect of chronic kidney disease (CKD) on collateral vessel
      development is not known. The purpose of this study was to evaluate the effect of
      CKD on collateral development in patients with advanced coronary artery disease.
      A total of 171 uraemic patients (serum creatinine > or = 1.5 mg/dl, creatinine
      clearance < 80 mL)/min) who underwent coronary angiography were evaluated in this
      study. A total of 134 patients met the criteria for the uraemic group and 134
      consecutive non-uraemic patients who constituted the control group. The
      collateral score (CS) was graded according to the Rentrop classification and the
      collateral score was calculated by summing the Rentrop numbers of every patient.
      Collateral vessels have also been categorized according to their anatomic
      locations and collateral connection grades (CC). CC2 collaterals were observed
      less frequently in the uraemic patients than in the control subjects (11% versus
      26%, p=0.03) and CC0 more frequently (31% versus 22%, p<0.05). Epicardial pathway
      was detected more frequently in the control subjects than in the uraemic patients
      (31% versus 12%, p=0.03) and septal pathway less frequently (37% versus 54%).
      There was a significant negative correlation between CS and creatinine (r=-0.68,
      p<0.01). The mean CS in the uraemic group was significantly lower than the non
      uraemic group (1.29+/-0.88 versus 2.18+/-1.3, p<0.001). These results altogether
      showed that besides the quantity, quality (functional, haemodynamic and anatomic
      features) of the uraemic collaterals and a network that they constitute is also
      impaired and different from the collaterals of the patient with normal renal
      function.

PMID- 16793152
TI  - Effect of microvascular reperfusion on prognosis and left ventricular function in
      anterior wall myocardial infarction treated with primary angioplasty.
AB  - BACKGROUND: Myocardial reperfusion in acute myocardial infarction may fail
      despite successful recanalization of the infarct-related artery. The purpose of
      this study was to assess the impact of myocardial reperfusion on clinical outcome
      and left ventricular (LV) function. METHODS: The clinical significance of
      myocardial blush grade (MBG)-angiographic marker of myocardial reperfusion, in
      104 patients (age 62+/-13 years) with first anterior myocardial infarction,
      successfully (TIMI 3) treated with primary angioplasty was analysed.
      Echocardiography was performed at baseline and after 6 months. Mortality and
      major cardiovascular event (MACE) rates were analysed 30 days and 1 year after
      acute myocardial infarction. Patients were divided into two groups according to
      presence (group 1, MBG 2-3, n=64) or absence of myocardial blush (group 2, MBG 0
      1, n=40). RESULTS: One-year mortality was significantly higher in group 2 in
      comparison to group 1 (22.5% vs 6.25%, HR: 3.6, 95% CI: 1.187-10.9, p=0.0175).
      The rate of MACE was significantly lower in patients with MBG 2-3, both after 1
      and 12 months (9.4% vs 30%, p=0.008 and 20.3% vs 60%, p<0.001, respectively). At
      baseline, both global and regional contractile function were significantly better
      in group 1 than in group 2 (ejection fraction (EF) 47.4+/-8.8% vs 43.3+/-7.9%,
      p=0.04 and wall motion score index (WMSI) 1.64+/-0.4 vs 1.87+/-0.3, p=0.001,
      respectively). Similarly, at 6 months follow-up, LV function was better in group
      1 as compared with group 2 (EF 54.9+/-14.5% vs 46+/-13.2%, p=0.005 and WMSI
      1.43+/-0.4 vs 1.76+/-0.46, p=0.001, respectively). CONCLUSIONS: Impaired
      microvascular reperfusion in patients with anterior myocardial infarction is
      associated with poor prognosis and worse early and late left ventricular
      function.

PMID- 16793153
TI  - Direct counting of Cryptosporidium parvum oocysts using fluorescence in situ
      hybridization on a membrane filter.
AB  - This report describes the development of a direct and rapid detection method for
      the pathogenic protozoan, Cryptosporidium parvum, from environmental water
      samples using fluorescence in situ hybridization (FISH) on a membrane filter. The
      hydrophilic polytetrafluoroethylene (PTFE) membrane filter with FISH-stained
      oocysts yielded the highest signal to noise (S/N) ratio of the different membrane
      filters tested. PTFE membranes retained 98.8+/-0.4% of the concentrated oocysts
      after washing, simultaneous permeabilization and fixation with a hot ethanol
      solution, and hybridization with a fluorescently labeled oligonucleotide probe.
      This procedure eliminates subsequent time-consuming recovery steps that often
      result in a loss of the actual oocysts in a given environmental water sample.
      Furthermore, C. parvum was successfully distinguished from Cryptosporidium muris
      and other species in environmental water samples with the addition of formamide
      into the hybridization solution. In tap water samples, the S/N ratio was
      heightened by washing the membrane filter prior to FISH with a 1 M HCl solution
      in order to reduce the large amounts of impurities and background fluorescence
      from the non-specific adsorption of the fluorescently labeled oligonucleotide
      probe.

PMID- 16793155
TI  - Running wheel exercises accelerate neuronal turnover in mouse dentate gyrus.
AB  - Neurogenesis continues throughout adulthood in mouse dentate gyrus, and is
      influenced by environmental, endocrine, and pharmacological conditions. Although
      running wheel exercises have been reported to enhance neurogenesis, the effects
      on neuronal death in dentate gyrus are not well understood. The precise control
      of the production and elimination of neurons is thought to be important for the
      maintenance of a relatively constant number of neurons in the adult nervous
      system and for the regulation of adult brain function. We report here that
      running wheel exercises enhance the death of pre-existing neurons as well as
      neurogenesis in dentate gyrus. In addition, we analyzed mice lacking an NMDA
      receptor varepsilon1 subunit, and found that the enhancement of the neuronal
      death by the exercises is suppressed in the varepsilon1 subunit knockout mice.
      These results suggest that running wheel exercises accelerate neuronal turnover
      in mouse dentate gyrus, through the activation of NMDA receptors.

PMID- 16793154
TI  - Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy x
      1) versus multiple fractions (3 Gy x 10) in the treatment of painful bone
      metastases.
AB  - BACKGROUND AND PURPOSE: To investigate whether single-fraction radiotherapy is
      equal to multiple fractions in the treatment of painful metastases. PATIENTS AND
      METHODS: The study planned to recruit 1000 patients with painful bone metastases
      from four Norwegian and six Swedish hospitals. Patients were randomized to single
      fraction (8 Gy x 1) or multiple-fraction (3 Gy x 10) radiotherapy. The primary
      endpoint of the study was pain relief, with fatigue and global quality of life as
      the secondary endpoints. RESULTS: The data monitoring committee recommended
      closure of the study after 376 patients had been recruited because interim
      analyses indicated that, as in two other recently published trials, the treatment
      groups had similar outcomes. Both groups experienced similar pain relief within
      the first 4 months, and this was maintained throughout the 28-week follow-up. No
      differences were found for fatigue and global quality of life. Survival was
      similar in both groups, with median survival of 8-9 months. CONCLUSIONS: Single
      fraction 8 Gy and multiple-fraction radiotherapy provide similar pain benefit.
      These results, confirming those of other studies, indicate that single-fraction 8
      Gy should be standard management policy for these patients.

PMID- 16793156
TI  - Variability among Bacillus cereus strains in spore surface properties and
      influence on their ability to contaminate food surface equipment.
AB  - Seven strains of Bacillus cereus isolated from the environment and from patients
      with diarrheic symptoms were examined from two angles: their spore surface
      properties, and their ability to adhere to stainless steel and to resist a
      cleaning in place (CIP) procedure. Our results revealed significant differences
      in their morphology (size of exosporium, length and number of appendages),
      hydrophobic character and surface protein composition. Most of these proteins
      originated in the vegetative cell and were tightly bound to the external surface
      of the exosporium such as EA1 or alanine racemase. Spore adhesion properties also
      varied from strain to strain. The ability to adhere was higher when spores were
      surrounded by long appendages, while the largest spores displayed the least
      resistance to cleaning. These observations suggest that food processing line
      contamination might be due to a given type of strain with specific surface
      properties (long appendages and small exosporium), which would represent an
      increased threat under the milder processing conditions required by consumers
      (minimally heat-treated foods for example) and by legal requirements (to limit
      effluents caused by hygiene procedures). Elsewhere, no clear relationship of the
      strain characteristics to the clinical vs. foodborne strains could be
      established.

PMID- 16793157
TI  - Shiga toxin-producing Escherichia coli in ground beef and lamb cuts: results of a
      one-year study.
AB  - Shiga toxin-producing Escherichia coli (STEC) have been associated with a broad
      spectrum of diarrhoeal syndromes. Some of these cases have been attributed to
      foods of bovine origin or other foods cross-contaminated by beef products or cow
      manure. The purpose of this study was to determine the pattern of STEC
      distribution in selected red meats over time. Samples of ground beef and lamb
      cuts were collected over a 52-week period from 31 different outlets and 25 g
      portions were assayed for STEC. STEC were isolated from 46/285 (16%) ground beef
      and 111/275 (40%) lamb samples using an stx PCR screen followed by colony
      hybridisation. All isolates were tested by PCR for additional STEC virulence
      markers with 95% of ground beef isolates shown to possess stx(2) and 80% of lamb
      cutlet isolates shown to possess stx(1) and stx(2). The enterohaemolysin gene
      (ehxA) was detected in 65% and 53% of ground beef and lamb isolates respectively.
      Putative enterohaemorrhagic E. coli (EHEC), i.e. STEC possessing the E. coli
      attaching and effacing gene (eae) were not isolated. The STEC isolates comprised
      18 and 15 different serotypes from ground beef and lamb respectively. STEC of
      serotypes O157, O111 and O26 (common enterohaemorrhagic E. coli serotypes) were
      not isolated. Serotypes O174 and O91 were the most common serotypes isolated from
      ground beef samples and O128 and O91 the most common from lamb cutlet samples.
      The presence of STEC in retail red meats highlights the need for a clearer
      understanding of STEC in food and human illness to interpret the public health
      significance of these findings.

PMID- 16793158
TI  - The effects on the microbiological condition of product of carcass dressing,
      cooling, and portioning processes at a poultry packing plant.
AB  - The log mean numbers of aerobes, coliforms, Escherichia coli and presumptive
      staphylococci plus listerias on chicken carcasses and carcass portions at various
      stages of processing at a poultry packing plant were estimated from the numbers
      of those bacteria recovered from groups of 25 randomly selected product units.
      The fractions of listerias in the presumptive staphylococci plus listerias groups
      of organisms were also estimated. Samples were obtained from carcasses by
      excising a strip of skin measuring approximately 5 x 2 cm(2) from a randomly
      selected site on each selected carcass, or by rinsing each selected carcass
      portion. The log mean numbers of aerobes, coliforms, E. coli and presumptive
      staphylococci plus listerias on carcasses after scalding at 58 degrees C and
      plucking were about 4.4, 2.5, 2.2 and 1.4 log cfu/cm(2), respectively. The
      numbers of bacteria on eviscerated carcasses were similar. After the series of
      operations for removing the crop, lungs, kidneys and neck, the numbers of aerobes
      were about 1 log unit less than on eviscerated carcasses, but the numbers of the
      other bacteria were not substantially reduced. After cooling in water, the
      numbers of coliforms and E. coli were about 1 log unit less and the numbers of
      presumptive staphylococci plus listerias were about 0.5 log unit less than the
      numbers on dressed carcasses, but the numbers of aerobes were not reduced. The
      numbers of aerobes were 1 log unit more on boneless breasts, and 0.5 log units
      more on skin-on thighs and breasts that had been tumbled with brine than on
      cooled carcasses; and presumptive staphylococci plus listerias were 0.5 log unit
      more on thighs than on cooled carcasses. Otherwise the numbers of bacteria on the
      product were not substantially affected by processing. Listerias were <20% of the
      presumptive staphylococci plus listerias group of organisms recovered from
      product at each point in the process except after breasts were tumbled with
      brine, when >40% of the organisms were listerias.

PMID- 16793159
TI  - On-line low-volume transesterification-based assay for immobilized lipases.
AB  - A method has been developed for fast evaluation of transesterification activity
      of immobilized lipases using microlitre and submicrolitre volumes of substrate
      solutions. The model reaction (acylation of isopropanol with vinyl acetate) is
      catalyzed by microbial lipases immobilized on ceramic particles, diatoms or
      acrylic resin, packed into a Teflon tube connected to fused-silica capillary
      tubing. The substrate solution is pumped through the microreactor and the product
      of transesterification, acetaldehyde, quantified on capillary by UV absorbance at
      280 nm. Using this system in the continuous-flow mode, comparisons were made of
      transesterification catalysed by PS-C II lipase in two different solvent
      mixtures. Acetonitrile was found to be a compatible solvent that can be used as a
      solubilizer without suppressing enzymatic activity. The method has been used to
      compare conversions at a fixed flow rate using a single pass of substrate through
      packed beds containing approximately 0.2 mg of supported enzyme. Spatial
      distributions of the product have been visualized using a complementary metal
      oxide semiconductor (CMOS) imaging detector in conjunction with the microreactor
      system operated in the stopped-flow mode.

PMID- 16793160
TI  - In vitro and in vivo evaluation of novel cationic liposomes utilized for cancer
      gene therapy.
AB  - Advanced peritoneal carcinomatoses is very difficult to treat. We have explored
      the potential therapeutic application of gene therapy using cationic liposomes in
      this disease. The lacZ gene was introduced in vitro into ovarian and endometrial
      cancer cells using cationic liposomes. The transfection efficiency was similar to
      that of commercially available liposomes in serum-free medium (11.0-20.9% vs. 5.4
      26.0%). In serum-containing medium, the efficiency was 1.9-18.1%, which is
      comparable with the efficiency in serum-free medium. However, the efficiency of
      commercial liposomes decreased drastically to between 0.1% and 4.7% in the serum
      containing medium. When cultured cells were transfected with the herpes simplex
      virus thymidine kinase (HSV-tk) gene and ganciclovir (GCV) was added, the anti
      tumor effect of GCV was 47-640 times greater than when the same experiment was
      performed with lacZ gene. Evaluation of anti-tumor effect was performed with the
      MTT assay. In vivo, the HRA and mEIIL ascitic mice were treated with HSV-tk gene
      and GCV using the peritoneal route, a significant prolongation of the mean
      survival time was observed by Kaplan-Meier analysis (16-18 days and 15-30 days,
      respectively, p < 0.05). These results indicate a potential role for gene therapy
      in the treatment of advanced intraperitoneal carcinomatoses using the novel
      cationic liposomes.

PMID- 16793162
TI  - Novel ultra-deformable vesicles entrapped with bleomycin and enhanced to
      penetrate rat skin.
AB  - Beta-sitosterol 3-beta-D-glucoside (Sit-G), an absorption enhancer, was
      incorporated into ultra-deformable vesicles containing bleomycin to attenuate
      drug toxicity in human keratinocytes. The presence of Sit-G increased drug
      entrapment and improved in vitro stability of ultra-deformable vesicles. Confocal
      laser scanning microscopy revealed the extent to which Sit-G facilitated the
      penetration of ultra-deformable vesicles containing fluorescent probes into rat
      skin upon non-occlusive topical application. Furthermore, treatment with
      preparations incorporating Sit-G resulted in elevated epidermal and dermal
      concentrations of bleomycin. Ultra-deformable formulation contained Sit-G
      maintained flexibility for penetration through the skin, increased entrapment
      efficiency of bleomycin and stability in vitro, and significantly increased
      distribution of bleomycin in epidermis and dermis compared with those without Sit
      G.

PMID- 16793161
TI  - Prophylactic anti-tumor effects in a B cell lymphoma model with DNA vaccines
      delivered on polyethylenimine (PEI) functionalized PLGA microparticles.
AB  - Idiotypic sequences, specific to the hypervariable regions of immunoglobulins
      expressed by malignant B cells offer a therapeutic target in B cell lymphoma.
      Efficient approaches have been described to clone a single chain fragment of the
      tumor immunoglobulin (Ig) comprising of heavy and light Ig chains (sFv) fused
      with proinflammatory chemokines. Tumor associated, poorly immunogenic self
      antigens encoded by plasmid DNA (pDNA) have been rendered immunogenic by
      chemokine fusion, thereby targeting to antigen presenting cells (APCs) which
      differentially express chemokine receptors. Here we present an injectable
      (parenteral) approach using synthetic polymer based cationic microparticle
      formulations for enhancing the potency of such chemokine/self antigen expressing
      plasmid construct. Branched and linear polyethyleneimine (PEI) were conjugated on
      poly (D, L lactide-co-glycolide) (PLGA) microparticles using carbodiimide
      chemistry followed by efficient loading of plasmid DNA. In addition to imparting
      significant buffering ability to these cationic microparticles, flow cytometry
      studies indicate that these DNA loaded microparticles significantly up regulate
      CD80 and MHC class II markers in phagocytic RAW264.7 cells, indicating intrinsic
      adjuvant effects. Intradermal injections in Balb/c mice with these formulations
      induced significant protection upon tumor challenge with 2.5 times the minimal
      lethal dose. Long term survival rates were significant (p < 0.05) in comparison
      with saline injected controls or blank microparticles. Further studies indicated
      that intramuscular delivery might provide better protection compared to
      intradermal injections and perform similar to gene gun mediated administration.
      We conclude, based on these promising in vivo results, that such surface
      functionalized microparticles offer an attractive strategy to improve the potency
      of self antigen-based cancer DNA vaccines.

PMID- 16793163
TI  - [The role of an information booklet or oral information about back pain in
      reducing disability and fear-avoidance beliefs among patients with subacute and
      chronic low back pain. A randomized controlled trial in a rehabilitation unit].
AB  - OBJECTIVES: To compare the efficacy of an information booklet or oral information
      about back pain in reducing disability and fear-avoidance beliefs among patients
      with subacute and chronic low back pain referred to a rehabilitation department.
      METHODS: An alternate-month design was used for 142 patients with subacute or
      chronic low back pain who were hospitalized for treatment. Seventy-two patients
      received written standardized information about back pain (the "back book") and
      usual physical therapy (intervention group), and 70 received usual physical
      therapy only along with nonstandardized oral information (control group). The
      main outcome measure was disability (measured on the Quebec back-pain disability
      scale), and secondary outcome measures were pain intensity (measured on a visual
      analog scale), fear-avoidance beliefs (measured on the Fear-Avoidance Beliefs
      Questionnaire [FABQ] Physical component), and knowledge of the relation of back
      pain to physical activity assessed at baseline, just before discharge from the
      hospital and 3 months after discharge. Satisfaction related to the information
      received was assessed on the day of discharge. RESULTS: Receiving the "back book"
      had a significant impact on disability at 3 months, from 48.40+/-14.55 to 34.57+/
      18.42 in the intervention group and from 52.17+/-16.88 to 42.40+/-14.95 in the
      control group (p=0.03). Receipt of the book also had a significant impact on
      patients' knowledge and satisfaction about information but a nonsignificant
      effect on fear-avoidance beliefs. CONCLUSIONS: Providing an information booklet
      about back pain to patients with subacute and chronic low back pain referred to a
      rehabilitation unit contributes to reduced disability in these patients.

PMID- 16793164
TI  - Early intrahepatic CD8 responses in HBV pathogenesis: a new piece of the puzzle.

PMID- 16793166
TI  - Hepatotoxicity due to extracts of Chinese green tea (Camellia sinensis): a
      growing concern.

PMID- 16793167
TI  - The emerging role of bile acids as integrators of intermediary metabolism.

PMID- 16793168
TI  - Predictions from a hard liver.

PMID- 16793169
TI  - Healthy public policy A conceptual cognitive framework.
AB  - More than three decades ago, the report A New Perspective on the Health of
      Canadians (1974) highlighted the significance of other determinants than the
      healthcare system. The adoption of healthy public policy was identified in the
      Ottawa Charter (1986) as one of five strategies aiming to promote health. It must
      now be acknowledged that even if we have a better understanding of health
      determinants, the latter are not necessarily taken into consideration when
      developing public policies. The purpose of this paper is to help foster a better
      understanding of the healthy public policies by presenting a conceptual framework
      that is inspired by the Advocacy Coalition Framework developed by Sabatier and
      Jenkins-Smith (1999). On the one hand, this paper intends to show the relevance
      of the notion of subsystem of public policies in healthy public policy process.
      On the other, it aims to convince that it is necessary to channel the analysis
      around the decision-making process, the prospective evaluation of public policies
      and the knowledge transfer and appropriation process. Finally, the purpose of
      this paper is to contribute to the ongoing debate about the role of knowledge,
      values or beliefs in the formulation and adoption of public policies. After
      briefly summarizing the theoretical developments in studies on public policies,
      the logic and components of the ACF are introduced. The main criticisms regarding
      the ACF are then examined, followed by an introduction of the conceptual
      framework that is adapted to the reality of healthy public policies. The notions
      of the subsystem of public policy(ies), of process and of learning process are
      central to this framework.

PMID- 16793171
TI  - Shifting responsibilities for food safety in Europe: an introduction.
AB  - Following the BSE crisis in 1996, the European food sector underwent profound
      regulatory and institutional change. The present introductory article introduces,
      and sketches the background to, seven studies of the institutional reactions and
      initiatives that were part of, or prompted by, this reorganisation. The studies
      analyse the way in which the division of responsibilities for food safety has
      changed both across the EU as a whole and, more specifically, in six European
      countries. Prepared as part of the comparative research project, Trust in Food,
      the studies attempt to go beyond traditional policy network analysis and work on
      regulation. They ask which constellations of societal actors and logics are
      important in the shifting responsibilities of public and private actors; and they
      treat this as an empirical question. It emerges that, at EU level, the main
      strategy for restoring consumer confidence in food was to enhance the
      institutional independence, transparency and consumer agency. In the countries
      covered by the remaining six studies, by contrast, institutional reactions in the
      food sector varied depending on the particular configurations of state, market
      and civil society.

PMID- 16793170
TI  - Enhanced reductive dechlorination in columns treated with edible oil emulsion.
AB  - The effect of edible oil emulsion treatment on enhanced reductive dechlorination
      was evaluated in a 14 month laboratory column study. Experimental treatments
      included: (1) emulsified soybean oil and dilute HCl to inhibit biological
      activity; (2) emulsified oil only; (3) emulsified oil and anaerobic digester
      sludge; and (4) continuously feeding soluble substrate. A single application of
      emulsified oil was effective in generating strongly reducing, anaerobic
      conditions for over 14 months. PCE was rapidly reduced to cis-DCE in all three
      live columns. Bioaugmentation with a halorespiring enrichment culture resulted in
      complete dechlorination of PCE to ethene in the soluble substrate column (yeast
      extract and lactate). However, an additional treatment with a pulse of yeast
      extract and bioaugmentation culture was required to stimulate complete
      dechlorination in the emulsion treated columns. Once the dechlorinating
      population was established, the emulsion only column degraded PCE from 90-120
      microM to below detection with concurrent ethene production in a 33 day contact
      time. The lower biodegradation rates in the emulsion treated columns compared to
      the soluble substrate column suggest that emulsified oil barriers may require a
      somewhat longer contact time for effective treatment. In the HCl inhibited
      column, partitioning of PCE to the retained oil substantially delayed PCE
      breakthrough. However, reduction of PCE to more soluble degradation products (cis
      DCE, VC and ethene) greatly reduced the impact of oil-water partitioning in live
      columns. There was only a small decline in the hydraulic conductivity (K) of
      column #1 (low pH+emulsion, K(final)/K(initial)=0.57) and column #2
      (live+emulsion, K(final)/K(initial)=0.73) indicating emulsion injection did not
      result in appreciable clogging of the clayey sand. However, K loss was greater in
      column #3 (sludge+emulsion, K(final)/K(initial)=0.12) and column #4 (soluble
      substrate, K(final)/K(initial)=0.03) indicating clogging due to biomass and/or
      gas production can be significant.

PMID- 16793172
TI  - Quantification of human angiotensinogen by a novel sandwich ELISA.
AB  - The urinary angiotensinogen excretion rates show a clear relationship to kidney
      angiotensin II content, suggesting that urinary angiotensinogen may serve as an
      index of angiotensin II-dependent hypertensive rats. However, simple and accurate
      methods to measure human angiotensinogen are unavailable at this time. We have
      developed two antibodies and a sensitive and specific quantification ELISA system
      for human angiotensinogen to be applicable to human subjects. The ELISA is able
      to detect human angiotensinogen at range of 0.01-1 microg/well (R(2)=0.9945)
      using standard ELISA plates. This ELISA will be a useful tool to investigate the
      relationship between urinary angiotensinogen excretion rates and reactivity to
      antihypertensive drugs in hypertensive human subjects.

PMID- 16793173
TI  - Neural interaction between galanin-like peptide (GALP)- and luteinizing hormone
      releasing hormone (LHRH)-containing neurons.
AB  - Galanin-like peptide (GALP), commonly known as an appetite-regulating peptide,
      has been shown to increase plasma luteinizing hormone (LH) through luteinizing
      hormone-releasing hormone (LHRH). This led us to investigate, using both light
      and electron microscopy, whether GALP-containing neurons in the rat brain make
      direct inputs to LHRH-containing neurons. As LHRH-containing neurons are very
      difficult to demonstrate immunohistochemically with LHRH antiserum without
      colchicine treatment, we used a transgenic rat in which LHRH tagged with enhanced
      green fluorescence protein facilitated the precise detection of LHRH-producing
      neuronal cell bodies and processes. This is the first study to report on synaptic
      inputs to LHRH-containing neurons at the ultrastructural level using this
      transgenic model. We also used immunohistochemistry to investigate the neuronal
      interaction between GALP- and LHRH-containing neurons. The experiments revealed
      that GALP-containing nerve terminals lie in close apposition with LHRH-containing
      cell bodies and processes in the medial preoptic area and the bed nucleus of the
      stria terminalis. At the ultrastructural level, the GALP-positive nerve terminals
      were found to make axo-somatic and axo-dendritic synaptic contacts with the EGFP
      positive neurons in these areas. These results strongly suggest that GALP
      containing neurons provide direct input to LHRH-containing neurons and that GALP
      plays a crucial role in the regulation of LH secretion via LHRH.

PMID- 16793174
TI  - A novel bradykinin-like peptide from skin secretions of rufous-spotted torrent
      frog, Amolops loloensis.
AB  - A bradykinin-like peptide has been isolated from skin secretions of rufous
      spotted torrent frog, Amolops loloensis. This bradykinin-like peptide was named
      amolopkinin. Its primary structure, RAPVPPGFTPFR, was determined by Edman
      degradation and mass spectrometry. It is structurally related to bradykinin-like
      peptides identified from skin secretions of other amphibians. Amolopkinin is
      composed of 12 amino acid residues and is related to bradykinin composed of nine
      amino acid residues, identified from the skin secretions of Odorrana schmackeri.
      Amolopkinin was found to elicit concentration-dependent contractile effects on
      isolated guinea pig ileum. cDNA clones encoding the precursor of amolopkinin were
      isolated by screening a skin cDNA library of A. loloensis and then sequenced. The
      amino acid sequences deduced from the cDNA sequences match well with the results
      from Edman degradation. Analysis of different amphibian bradykinin cDNA
      structures revealed that a deficiency of an18-nucleotide fragment
      (TCAAGAATGATCAGACGC in the cDNA encoding bradykinin from O. schmackeri) in the
      peptide-coding region resulted in absence of a di-basic site for trypsin-like
      proteinases and an unusual - APV - insertion in the N-terminal part of
      amolopkinin. This is the first report of a bradykinin-like peptide comprised of
      bradykinin with an insertion in its N-terminal part. Our results demonstrate the
      hypervariability of amphibian bradykinin-like peptides, as well as the diversity
      of antimicrobial peptides in amphibians.

PMID- 16793175
TI  - Carrier-mediated delivery of peptidic drugs for cancer therapy.
AB  - Protein and peptide drugs are used for treatment of a variety of ailments.
      However, their wider use has been hindered by issues such as poor bioavailability
      in vivo and the cost involved in producing these drugs. This review discusses the
      various carrier-mediated methods used for delivery of peptide and protein drugs,
      with emphasis on liposomal and microspherical drug delivery systems. A brief look
      at the types of peptidic drugs currently in use clinically, and a brief discourse
      on several novel ideas for better protein delivery systems for cancer therapy is
      included.

PMID- 16793176
TI  - Age-related neuronal loss in the submucosal plexus of the colon of Fischer 344
      rats.
AB  - The submucosal plexus (SMP) of the large intestine plays important roles in
      secretion and motility, functions that are compromised in the aged. To determine
      the effects of aging on intrinsic SMP neurons and their extrinsic inputs, whole
      mounts from the colon of ad libitum fed virgin male Fischer 344 rats ranging in
      age from 6 to 27 months were processed to visualize neurons and nerve fibers
      immunoreactive for either tyrosine hydroxylase (TH-IR) or calcitonin gene-related
      peptide (CGRP-IR). Significant age-related loss of SMP neurons occurred as early
      as 12 months of age and progressed in a roughly linear manner with age, dropping,
      for example, by 38% in the distal colon. In aging rats, the colonic SMP routinely
      contained markedly swollen TH-IR axons and terminals and exhibited a reduction of
      ganglionic neuropil, whereas CGRP-IR fibers evidenced only modest axonopathies.
      These findings point to selective deterioration of the SMP and its extrinsic
      inputs as one possible mechanism for the age-related decline in large intestinal
      function evidenced in the elderly.

PMID- 16793177
TI  - The temporal window of integration in elderly and young adults.
AB  - Integration of information across time is an essential part of auditory
      processing. Evidence from a variety of experiments support the notion of an
      approximately 200-ms long time window following the onset of a sound, during
      which a unitary sound representation is formed (the temporal window of
      integration, TWI). The temporal resolution in the auditory system is assumed to
      decrease with aging suggesting that the duration of the TWI may be longer in
      elderly than young adults. The TWI duration was assessed in young and elderly
      adults using the oddball paradigm in which a regular auditory event (standard) is
      occasionally exchanged for a different event (deviant). Previous studies showed
      that when the stimulus onset asynchrony (SOA) exceeds the duration of the TWI,
      two successive deviations occurring infrequently in a repetitive sound sequence
      elicit two separate mismatch negativity (MMN) event-related brain potentials.
      However, only one MMN is elicited when the SOA is shorter than the TWI.
      Experiment 1 tested MMN elicitation for the second of two successive deviant
      sounds as a function of the SOA. Experiment 2 used the sound omission paradigm,
      in which MMN is only elicited by omissions when the SOA is shorter than the TWI.
      Again, MMN elicitation was tested by infrequent tone omissions as a function of
      the SOA. Results showed no significant differences between elderly and younger
      participants as a function of SOA. This suggests that the duration of the TWI is
      approximately between 200 and 250 ms in both groups of subjects. On the other
      hand, the lower MMN amplitudes elicited by frequency deviation in the elderly
      compared with the younger participants suggest that the specificity of frequency
      representation deteriorates with aging.

PMID- 16793178
TI  - Synthesis of phenanthridinium-bis-nucleobase conjugates, interactions with poly
      U, nucleotides and in vitro antitumour activity of mono- and bis-nucleobase
      conjugates.
AB  - Novel bis-nucleobase-phenanthridinium conjugates were synthesised and their
      aqueous solutions spectroscopically characterised. Bis-adenine conjugate revealed
      in aqueous solutions significantly more pronounced intramolecular aromatic
      stacking interactions than bis-uracil analogue. In contrast with previously
      reported poly A recognition by bis-uracil conjugate, recognition of complementary
      nucleotides and poly U was not observed due to the strong interference of bulk
      water with hydrogen bonding between nucleobases. The screening of anticancer
      activity on six human cell lines revealed that tethering of a nucleobase to
      phenanthridinium moiety diminished antiproliferative potential of
      phenanthridinium. However, among mono-nucleobase conjugates adenine derivative
      was found to be the most selective one (MiaPaCa-2, Hep-2).

PMID- 16793179
TI  - [Living... challenging our limits. Is wisdom a drug against feeling unease].

PMID- 16793180
TI  - [Edema of the heel].

PMID- 16793181
TI  - Overlapping synthetic peptides as vaccines.
AB  - Several vaccine strategies aim to generate cell-mediated immunity (CMI) against
      microorganisms or tumors. While epitope-based vaccines offer advantages,
      knowledge of specific epitopes and frequency of major histocompatibility complex
      (MHC) alleles is required. Here we show that using promiscuous overlapping
      synthetic peptides (OSP) as immunogens generated peptide-specific CMI in all
      vaccinated outbred mice and in different strains of inbred mice; CMI responses
      also recognized viral proteins. OSP immunogens also induced CMI ex vivo in
      dendritic cell/T-cell cocultures involving cells from individuals with different
      HLA haplotypes. Thus, broad CMI was induced by OSP in different experimental
      settings, using different immunogens, without identifying either epitopes or MHC
      backgrounds of the vaccinees.

PMID- 16793182
TI  - Classification of soil samples according to their geographic origin using gamma
      ray spectrometry and principal component analysis.
AB  - A principal component analysis (PCA) was used for classification of soil samples
      from different locations in Serbia and Montenegro. Based on activities of
      radionuclides ((226)Ra, (238)U, (235)U, (40)K, (134)Cs, (137)Cs, (232)Th and
      (7)Be) detected by gamma-ray spectrometry, the classification of soils according
      to their geographical origin was performed. Application of PCA to our
      experimental data resulted in satisfactory classification rate (86.0% correctly
      classified samples). The obtained results indicate that gamma-ray spectrometry in
      conjunction with PCA is a viable tool for soil classification.

PMID- 16793183
TI  - Shoot growth of mature Fagus sylvatica and Picea abies in relation to ozone.
AB  - Epidemiological analysis of sequential growth data may be a tool in assessing
      ozone sensitivity of mature trees. Annual shoot growth of mature Fagus sylvatica
      in 83 Swiss permanent forest observation plots and of Picea abies in 61 plots was
      evaluated for 11 and 8 consecutive years, respectively, using branches harvested
      every 4 years. The data were assessed as annual deviation from average growth and
      related to fructification, ozone, meteorological parameters, and modelled soil
      water content using a mixed linear model. In beech, a significant association
      between ozone and shoot growth was observed which corresponded to a 7.4% growth
      reduction between 0 and 10 ppm h AOT40 (accumulated ozone over threshold 40).
      This is in the same order of magnitude as the response observed in experiments
      with seedlings. No interaction was found between ozone and drought parameters. In
      Norway spruce, shoot growth was neither associated with ozone nor with drought.

PMID- 16793184
TI  - Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory
      perspective.
AB  - Haemolytic anaemia is often induced following prolonged exposure to chemical
      substances. Currently, under EU Council Directive 67/548/EEC, substances which
      induce such effects are classified as dangerous and assigned the risk phrase R48
      'Danger of serious damage to health by prolonged exposure.' Whilst the general
      classification criteria for this endpoint are outlined in Annex VI of this
      Directive, they do not provide specific information to assess haemolytic anaemia.
      This review produced by the EU Working Group on Haemolytic Anaemia provides a
      toxicological assessment of haemolytic anaemia and proposes criteria that can be
      used in the assessment for classification of substances which induce such
      effects. An overview of the primary and secondary effects of haemolytic anaemia
      which can occur in rodent repeated dose toxicity studies is given. A detailed
      analysis of the toxicological significance of such effects is then performed and
      correlated with the general classification criteria used for this endpoint. This
      review intends to give guidance when carrying out an assessment for
      classification for this endpoint and to allow for better transparency in the
      decision-making process on when to classify based on the presence of haemolytic
      anaemia in repeated dose toxicity studies. The extended classification criteria
      for haemolytic anaemia outlined in this review were accepted by the EU Commission
      Working Group on the Classification and Labelling of Dangerous Substances in
      September 2004.

PMID- 16793185
TI  - The influence of child abuse on the pattern of expenditures in women's adult
      health service utilization in Ontario, Canada.
AB  - Childhood maltreatment is a common and serious problem for women, particularly in
      relation to impairment in adulthood. To our knowledge, no system-wide study has
      addressed the influence of childhood maltreatment on the cost of these women's
      adult health service utilization. This paper examines this relationship. The 1990
      Ontario Health Survey (OHS) gathered information regarding determinants of
      physical health status and the use of health services. The 1991 Ontario Mental
      Health Supplement (OHSUP) examined a variety of childhood experiences as well as
      the prevalence of psychiatric disorders from a sample of OHS respondents. These
      were province-wide population health surveys of a probability-based sample of
      persons aged 15 years and older living in household dwellings in Ontario. The
      OHSUP randomly selected one member from each participating OHS household to be
      interviewed regarding personal experiences and mental health. This analysis used
      data from women aged 15-64 who participated in both the OHS and OHSUP. Self
      reported health service utilization was collected in four groups of women--those
      who reported no history of child abuse, those with a history of physical abuse
      only, those who reported sexual abuse only, and those who reported both physical
      and sexual (combined) abuse. We hypothesized that a history of child abuse would
      result in greater adult health care costs. The results indicated that having a
      history of combined abuse nearly doubles mean annual ambulatory self-reported
      health care costs to 775 dollars (95% CI 504 dollars-1045 dollars) compared to a
      mean cost of 400 dollars with no abuse (95% CI 357 dollars-443 dollars). Median
      annual ambulatory self-reported health care costs were also increased in the
      combined abuse group, to 314 dollars (95% CI 220 dollars-429 dollars), compared
      to 138 dollars (95% CI 132 dollars-169 dollars) in those with no abuse. We
      conclude that child abuse in women is significantly associated with increased
      adult self-reported health care costs.

PMID- 16793186
TI  - Conceptual priming for environmental sounds and words: an ERP study.
AB  - In this study we examined conceptual priming using environmental sounds and
      visually displayed words. Priming for sounds and words was observed in response
      latency as well as in event-related potentials. Reactions were faster when a
      related word followed an environmental sound and vice versa. Moreover both
      stimulus types produced an N400-effect for unrelated compared to related trials.
      The N400-effect had an earlier onset for environmental sounds than for words. The
      results support the theoretical notion that conceptual processing may be similar
      for verbal and non-verbal stimuli.

PMID- 16793187
TI  - Dysregulation of tau phosphorylation is a hypothesized point of convergence in
      the pathogenesis of alzheimer's disease, frontotemporal dementia and
      schizophrenia with therapeutic implications.
AB  - Two members of the family of low-density lipoprotein receptors (i.e., very low
      density lipoprotein [VLDL] receptor and apolipoprotein E [apoE] type 2 receptor)
      are expressed in brain, where they bind and transduce reelin, a secreted
      glycoprotein that shares structural analogies with extracellular matrix proteins.
      In the developing fetal brain, reelin-signal transduction is critical for the
      correct positioning of neurons and the formation of appropriate synaptic
      connections, whereas in the mature brain, reelin participates in the mediation of
      experience-dependent synaptic plasticity. An important "downstream" consequence
      of the reelin-signal transduction cascade is inhibition of the phosphorylation of
      tau, a protein that regulates microtubule assembly and stability. Importantly,
      hyperphosphorylated tau comprises the paired helical filament, whose pathological
      deposition as neurofibrillary tangles is implicated in Alzheimer's disease;
      hyperphosphorylated tau is also implicated in the pathogenesis of other
      neurodegenerative disorders. Isoforms of apoE may affect the binding of reelin to
      its cell surface receptors and, thereby, influence tau phosphorylation, whereas
      insulin, insulin-like growth factor-1, and the lithium ion have actions within
      the cell at the level of the specific tyrosine kinases involved in the
      phosphorylation of tau. These data support the exploration of pharmacotherapeutic
      interventions designed to prevent or reduce the burden of hyperphosphorylated
      tau. Impaired reelin-signal transduction due to an actual deficiency of reelin
      expression may occur in at least some patients with psychotic disorders,
      especially schizophrenia; conceivably, hyperphosphorylation of tau would result
      from deficient transduction of reelin in schizophrenia. Schizophrenia has been
      conceptualized as a neurodevelopmental disorder of impaired synaptic
      "connectivity", whose consequence does not become fully apparent until late
      adolescence or early adulthood. In summary, hyperphosphorylation of tau may be an
      underlying point of pathological convergence for several neuropsychiatric
      disorders, and prevention of tau hyperphosphorylation may be an important
      therapeutic target.

PMID- 16793188
TI  - Administration of antisense DNA for ghrelin causes an antidepressant and
      anxiolytic response in rats.
AB  - RATIONALE: Ghrelin is a peptide of 28 amino acids found in mammals that increases
      the release of growth hormone, food intake, and body weight. OBJECTIVES: We
      investigated the relationship between ghrelin and the states of anxiety and
      depression by giving rats either antisense DNA for ghrelin, scrambled DNA or
      vehicle into the lateral ventricle of rats. RESULTS: In forced swimming tests,
      rats that received antisense DNA decreased the length of time that they were
      immobile in the water. Ghrelin antisense oligonucleotides produced an anxiolytic
      like effects in the elevated plus maze test, black and white test, or conditioned
      fear tests. Treatment with antisense DNA for ghrelin significantly decreased rat
      body weight. No significant effect on general locomotor activity was seen.
      CONCLUSIONS: These results suggest that administration of antisense DNA for
      ghrelin causes an antidepressant and anxiolytic response in rats.

PMID- 16793189
TI  - Glutathione plays a role in regulating the formation of toxic reactive
      intermediates from diphenylarsinic acid.
AB  - The role of glutathione (GSH) in the cytotoxicity of diphenylarsinic acid
      [DPAA(V)], which was detected in drinking well water after a poisoning incident
      in Kamisu, Japan, was investigated in cultured human HepG2 cells. DPA-GS(III),
      which is the GSH adduct of DPAA, was synthesized and analyzed by HPLC/ESI-MS. DPA
      GS(III) was highly toxic to cells and the potency was about 1000 times that of
      DPAA(V). DPAA(V) was stable in culture medium, while DPA-GS(III) was unstable and
      changed to protein-bound As (protein-As). By contrast, DPA-GS(III) remained
      stable with the addition of exogenous GSH, thereby reducing transformation to
      protein-As. In addition, DPA-GS(III) was transformed to bis(diphenylarsine)oxide
      [BDPAO(III)], which was observed under serum-free conditions. BDPAO(III) was very
      unstable and disappeared conversely with an increase in protein-As. In contrast,
      the presence of GSH suppressed the transformation of BDPAO(III) to protein-As
      while it enhanced the transformation of BDPAO(III) to DPA-GS(III). Depletion of
      cell GSH enhanced the cytotoxic effects of DPA-GS(III) and BDPAO(III). Moreover,
      exogenously-added GSH suppressed the cytotoxic effects of DPA-GS(III) and
      BDPAO(III). The dynamic behavior of arsenicals in the culture medium and the
      resultant cytotoxic effects suggested that GSH played a role in regulating the
      formation of toxic intermediates, such as DPA-GS(III) and BDPAO(III). Moreover,
      the results suggested that the formation of protein-As in culture medium was
      compatible with the cytotoxic effects and that GSH was a factor capable of
      regulating the formation of protein-As from either DPA-GS(III) or BDPAO(III).

PMID- 16793190
TI  - p38 Mitogen-activated protein kinase up-regulates LPS-induced NF-kappaB
      activation in the development of lung injury and RAW 264.7 macrophages.
AB  - Clarification of the key regulatory steps that lead to nuclear factor-kappa B (NF
      kappaB) under cellular and pathological conditions is very important. The action
      of p38 mitogen-activated protein kinase (MAPK) on the upstream of NF-kappaB
      activation remains controversial. To examine this issue using an in vivo lung
      injury model, SB203580, a p38 MAPK inhibitor was given intraorally 1h prior to
      lipopolysaccharide (LPS) treatment (intratracheally). The mice were sacrificed 4
      h after LPS treatment. SB203580 substantially suppressed LPS-induced rises in p38
      MAPK phosphorylation, neutrophil recruitment, total protein content in
      bronchoalveolar lavage fluid, and apoptosis of bronchoalveolar cells.
      Furthermore, SB203580 blocked LPS-induced NF-kappaB activation in lung tissue
      through down-regulation of serine phosphorylation, degradation of IkappaB-alpha,
      and consequent translocation of the p65 subunit of NF-kappaB to the nucleus. It
      is likely that, in cultured RAW 264.7 macrophages, SB203580 also blocked LPS
      induced NF-kappaB activation in a dose-dependent manner. SB203580 inhibited LPS
      induced serine phosphorylation, degradation of IkappaB-alpha, and tyrosine
      phosphorylation of p65 NF-kappaB. These data indicate that p38 MAPK acts upstream
      of LPS-induced NF-kappaB activation by modulating the phosphorylation of IkappaB
      alpha and p65 NF-kappaB during acute lung injury. Because LPS-stimulated
      macrophages may contribute to inflammatory lung injury, the inhibition of the p38
      MAPK-mediated intracellular signaling pathway leading to NF-kappaB activation
      represents a target for the attenuation of lung inflammation and parenchymal
      damage.

PMID- 16793191
TI  - EJ-ras oncogene transfection of endothelial cells upregulates the expression of
      syndecan-4 and downregulates heparan sulfate sulfotransferases and epimerase.
AB  - The EC rabbit endothelial cell line was transfected with the EJ-ras oncogene (EJ
      ras EC). EJ-ras EC cells display over expression of the Ras oncogene,
      morphological changes and deregulation of the cell cycle, becoming more densely
      populated and serum-independent. In addition, EJ-ras-transfectant cells show
      higher levels of the syndecan-4 mRNA. In addition to the increase in the core
      protein, a parallel increase in the glycosylation of the syndecan-4 protein, a
      proteoglycan that bears heparan sulfate chains, also occurs. This increase is
      observed both for the heparan sulfate proteoglycan synthesized by the cells and
      for that secreted to the culture medium. This enhancement in heparan sulfate
      synthesis was observed through metabolic labeling of the cells,
      immunoprecipitation of syndecan-4 and heparitinases treatment. Furthermore, the
      EJ-ras-transfectant cells do not exhibit decreased synthesis of heparan sulfate
      during the G(1)-S phase transition, as observed for the parental cell line. Also,
      heparan sulfate synthesis is not stimulated by PMA as displayed by parental
      endothelial cells. Significant structural changes of heparan sulfate, such as
      decreased O-sulfation, were observed in the EJ-ras-transfected cells. Decreases
      in the mRNA levels of some enzymes (glucuronosyl C-5 epimerase, iduronosyl-2-O
      sulfotransferase, glucosaminyl-6-O-sulfotransferase-1 and N-deacetylase/N
      sulfotransferase-1), involved in the biosynthetic pathway of heparan sulfate,
      were also observed. The results suggest that overexpression of the EJ-ras
      oncogene alters the cell cycle, through signal transduction cascades, upregulates
      the expression of syndecan-4, and downregulates enzymes involved in the heparan
      sulfate biosynthesis related to chain modification, leading to the structural
      changes of the heparan sulfate syndecan-4 proteoglycan in endothelial cells.

PMID- 16793192
TI  - Purification, characterization and cytokine release function of a novel Arg-49
      phospholipase A(2) from the venom of Protobothrops mucrosquamatus.
AB  - Group IIA phospholipase A(2) (PLA(2)) are major components in
      Viperidae/Crotalidae venom. In the present study, a novel PLA(2) named promutoxin
      with Arg at the site 49 has been purified from the venom of Protobothrops
      mucrosquamatus by chromatography. It consists of 122 amino acid residues with a
      molecular mass of 13,656 Da assessed by MALDI-TOF. It has the structural features
      of snake venom group IIA PLA(2)s, but has no PLA(2) enzymatic activity.
      Promutoxin shows higher amino acid sequence identity to the K49 PLA(2)s (72-95%)
      than to D49 PLA(2)s (52-58%). Promutoxin exhibits potent myotoxicity in the
      animal model with as little as 1 microg of promutoxin causing myonecrosis and
      myoedema in the gastrocnemius muscle of mice. Promutoxin is also able to
      stimulate the release of IL-12, TNFalpha, IL-6 and IL-1beta from human monocytes,
      and induce IL-2, TNFalpha and IL-6 release from T cells, indicating that this
      snake venom group IIA PLA(2) is actively involved in the inflammatory process in
      man caused by snake venom poisoning.

PMID- 16793193
TI  - Sexual intercourse: an unusual cause of rectovaginal fistula.

PMID- 16793194
TI  - Trans-obturator urethral sling for the surgical correction of female stress
      urinary incontinence: outside-in (Monarc) versus inside-out (TVT-O). Are the two
      ways reassuring?
AB  - INTRODUCTION: In 2001, the trans-obturator route was proposed for the surgical
      positioning of tape with a view to avoiding the retropubic space and its
      disadvantages. The route, originally described outside-in by Delorme was
      presented inside-out by de Leval. Since then, anatomical discussions have
      attempted to prove that one technique is safer than the other. OBJECTIVE:
      Demonstrating the safety of the two techniques through personal and published
      experience. MATERIAL AND METHODS: Non-randomized, prospective, observational,
      open-label, longitudinal study of 100 female patients (50 tension-free vaginal
      tape (TVT)-O and 50 Monarc). All the female patients presented with isolated
      stress urinary incontinence. Only four patients presented with mixed incontinence
      in the Monarc (MON) group. Sphincter incompetence was observed four times in the
      MON group and three times in the TVT-O group. Almost all the patients were
      undergoing their first procedure. All the patients underwent surgery under
      assisted local anesthesia in a day-hospital setting. All the patients underwent a
      full gynecological examination and a urodynamic assessment. Only those patients
      presenting with patent established urinary incontinence, corrected by the TVT
      test, underwent surgery. Post-operative control was conducted at 3 months and 1
      year when a physical examination and urodynamic assessment were implemented.
      RESULTS: All the patients underwent control up to time point 12 months. The
      duration of hospitalization was 10h for 48 patients in the MON group and 49 in
      the TVT-O group. The duration of hospitalization was 24h for one patient in each
      group and 4 days for one patient in the TVT-O group due to transient urine
      retention. The only per-operative complication was a vaginal perforation in the
      lateral angle of the vagina for a MON patient. Tape repositioning was necessary.
      Early post-operative complications were observed in the MON group: three cases of
      urinary tract infection, one of transient urine retention, three of pain in the
      thighs spontaneously resolving within 4 days and one of permanent pain in one leg
      at time 1 year, which remained bearable. For the TVT-O group the post-operative
      complications consisted in: one case of urinary tract infection, one of transient
      retention and four of pain in the thigh. No hematoma was reported in either
      group. Amongst the late complications, the de novo symptoms included one case of
      imperious urges to urinate in the TVT-O group and objective dysuria in two cases
      in the MON group versus seven in the TVT-O group. There was no statistically
      significant between-group difference in the complications. No tape exposure was
      observed. Overall, the recovery rate was 90% at 1 year for MON versus 94% for TVT
      O (p=NS) with two cases of recurrence between 3 months and 1 year in that series.
      Mixed incontinence was corrected at time point 1 year in 75% of cases for MON,
      with one case of recurrence in the year. For the patients presenting with
      sphincter incompetence, competence was maintained at 3 months and 1 year in all
      cases in the MON group. The three TVT-O were cured at 3 months, but two
      recurrences were observed at 1 year. Almost all the patients were satisfied or
      very satisfied at time point 1 year and those who had sexual relations (54%) did
      not report any disorder at time point 1 year. DISCUSSION: The outside-in
      technique necessitates more marked peri-urethral dissection and vesical
      complications are possible. The cadaveric studies by the outside-in partisans
      show a vascular and nervous risk, which has little reflection in terms of
      complications in the literature. Post-operative leg pains are encountered with
      both techniques and are usually only transient. All the studies of the two routes
      report a recovery rate of over 90% for pure stress incontinence. CONCLUSION: The
      author's experience, like that reported in the literature, shows that the two
      trans-obturator access routes are equally safe and do not require per-operative
      cystoscopic control. The clinical results would appear to be equivalent, in terms
      of recovery, to the rates obtained with retropubic TVT. Attempting to find
      anatomical or etiological arguments in order to prove one technique superior to
      the other appears somewhat parochial.

PMID- 16793195
TI  - Ionic volumes in solution.
AB  - The volumetric properties of electrolytes in solutions indicate the interactions
      of the constituent ions with their environment: the solvent and other ions. The
      interactions with the solvent alone are manifested at infinite dilution by the
      standard partial molar volume, V(infinity)(salt), obtained from density
      measurements. To study the interactions, it is necessary to split
      V(infinity)(salt) into the additive ionic contributions, V(infinity)(ion), using
      an extra-thermodynamic assumption. Values of V(infinity)(ion) for small ions
      depend cardinally on the electrostriction of the solvent that can be obtained
      from an iterative shell-by-shell calculation from a continuum model of the
      solvent. The solvent shrinkage per mol of ions is DeltaV(el)(ion)<0. Also, the
      molar electrostriction of the solvent S, DeltaV(el)(S)<0, is calculable. The
      ratio DeltaV(el)(ion)/DeltaV(el)(S)=n(infinity) is the solvation number of the
      ion in S at infinite dilution. The calculated V(infinity)(ion)(calc) are compared
      with the experimental values, showing good agreement for many univalent ions in
      both single solvents and in some binary solvent mixtures, where no appreciable
      preferential solvation takes place. Ion pairing sets in under certain
      circumstances of ionic charge and solvent permittivity. The difference
      DeltaV(ip)=V(ip)(infinity)-[V(infinity)(+)+V(infinity)(-)]>0 is obtained
      experimentally from the pressure derivative of the association constant. The
      ratio Deltan(ip)=DeltaV(ip)/DeltaV(el)(S) represents the number of solvent
      molecules released to the bulk on ion pairing by the diminution of the
      electrostriction.

PMID- 16793196
TI  - Improving efficacy of intravesical chemotherapy.
AB  - OBJECTIVE: This paper reviews the most relevant findings published recently on
      intravesical chemotherapy for superficial bladder tumours and provides
      recommendations based on documented research. METHODS: The evidence was
      categorised according to the North of England Evidence Based Guideline
      Development Project. Levels of evidence were based on the source of the
      information, meta-analyses, systematic reviews, well-designed randomised or
      nonrandomised controlled clinical trials, and uncontrolled studies or consensus.
      Three levels of recommendations were assigned to the evidence obtained. RESULTS:
      Despite intravesical chemotherapy being used prophylactically after endoscopic
      resection of superficial bladder tumours, the recurrence rate is still 36-44%.
      Researchers have focused on improving the effectiveness of intravesical
      chemotherapy, each adopting a different strategy. Some have aimed to identify the
      optimum timing for instillations and others to improve the pharmacokinetics of
      agents by avoiding their dilution, increasing their stability, or improving the
      absorption of the drug by bladder mucosa. Some researchers are looking into new,
      single chemotherapeutic agents or combinations for intravesical use and others
      into avoiding chemoresistance with resistance-reverting agents (modulating
      agents) or by using in vitro chemosensitivity tests to identify the most
      sensitive drug. CONCLUSION: Progress has been made in optimising intravesical
      chemotherapy for timing of instillations and pharmacokinetic interventions.
      Simple and inexpensive approaches may have a widespread, practical acceptance by
      urologists, but it is more difficult to extend new techniques requiring more
      complex and sometimes expensive instrumentation to the urologic community.
      Further research into finding more effective cytotoxic drugs, combinations, or
      modulating agents should be encouraged.

PMID- 16793197
TI  - Discrepancy between clinical and pathologic stage: impact on prognosis after
      radical cystectomy.
AB  - OBJECTIVES: We compared clinical and pathologic staging in a large, contemporary,
      consecutive series of patients who were treated with radical cystectomy and
      pelvic lymphadenectomy, and determined the effect of stage discrepancy on
      outcomes. METHODS: We collected retrospective data from 778 consecutive patients
      with bladder transitional cell carcinoma who were treated with radical cystectomy
      and pelvic lymphadenectomy, and for whom the clinical and pathologic stage were
      available. RESULTS: Pathologic upstaging occurred in 42% of patients, and
      pathologic downstaging occurred in 22%. Forty percent of patients with non-muscle
      invasive clinical stage had muscle-invasive pathologic stage. Thirty-six percent
      of patients with organ-confined clinical stage had non-organ-confined pathologic
      stage (> or =pT3N0 or pTanyN-positive). Patients with higher clinical stage were
      more likely to be upstaged to non-organ-confined disease (p<0.001). Patients were
      stratified into three groups: pathologically upstaged, same clinical and
      pathologic stage, and pathologically downstaged. When adjusted for the effects of
      standard postoperative features, upstaged patients were at a significantly higher
      risk of disease recurrence and bladder cancer-specific death than patients who
      had the same pathologic and clinical stage, who in turn were at significantly
      higher risk than downstaged patients. This observation remained true within each
      clinical stage strata. Within each pathologic stage strata, clinical stage did
      not substratify into different risk groups. CONCLUSIONS: Clinical to pathologic
      stage discrepancy is a relatively common finding after extirpative surgery for
      bladder cancer. Clinical outcomes after radical cystectomy are largely driven by
      pathologic stage. Better clinical staging is necessary to improve patient
      evaluation and management.

PMID- 16793198
TI  - Lesions of suprachiasmatic nucleus efferents selectively affect rest-activity
      rhythm.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus controls circadian rhythms
      in behavioral, neuroendocrine and physiological functions. In this study, we test
      the hypothesis that caudal SCN efferents to the subparaventricular zone (SPVZ)
      control the rhythm in rest-activity (R-A) through projections on posterior
      hypothalamic area arousal systems (PHA). Small electrolytic lesions of the
      ventral SPVZ cause a selective loss of the circadian R-A rhythm, sparing the core
      body temperature rhythm. In contrast, large excitotoxic lesions of the posterior
      hypothalamic area (PHA) that effectively ablate populations of hypocretin and
      melanin concentrating hormone neurons projecting to cortex and subcortical
      arousal areas decrease R-A rhythm amplitude but do not disrupt circadian
      regulation. Since dorsomedial hypothalamic nucleus lesions have effects similar
      to PHA lesions (Chou, T.C., Scammell, T.E., Gooley, J.J., Gaus, S.E., Saper,
      C.B., Lu, J., 2003. Critical role of dorsomedial hypothalamic nucleus in a wide
      range of behavioral circadian rhythms. J. Neurosci. 23:10691-10702), these data
      support the view that the SPVZ is the principal relay nucleus for SCN signals to
      the multiple posterior hypothalamic arousal systems involved in generation of the
      R-A rhythm.

PMID- 16793199
TI  - Diffusion tensor imaging for differentiation of recurrent brain tumor and
      radiation necrosis after radiotherapy--three case reports.
AB  - Fractional anisotropy (FA) is influenced by histological data such as
      cellularity, vascularity and/or fiber structure in astrocytic tumors. We describe
      two patients with tumor recurrence and one patient with radiation necrosis who
      were diagnosed using assessment of FA value. The assessment of FA value in
      enhanced lesions after radiotherapy may be able to differentiate radiation
      necrosis from tumor recurrence.

PMID- 16793200
TI  - A five-generation family with occipital encephalocele.
AB  - This study reports a Chinese family that has suffered from occipital
      encephalocele over five generations with a pattern of autosomal dominant
      inheritance. There were 113 family members in this family, and 21 of them had an
      occipital subscalp encephalocele. The patients with the disease showed normal or
      nearly normal neurological function.

PMID- 16793201
TI  - Inflammation or neoplasm? Another side to the story.

PMID- 16793202
TI  - A new mucin antibody/enzyme-linked lectin-sandwich assay of serum MUC5AC mucin
      for the diagnosis of cholangiocarcinoma.
AB  - We have previously used agarose gel electrophoresis and immunoblotting to
      qualitatively measure serum MUC5AC mucin for diagnosing cholangiocarcinoma. In
      this study, we developed a quantitative determination of serum MUC5AC by sandwich
      ELISA using MUC5AC mucin monoclonal antibody and soybean agglutinin. A cut-off
      value of the absorbance 0.074 was obtained from a complete statistical Receiver
      Operating Characteristic curves with an area under the curve=0.8141. The assay
      could discriminate cholangiocarcinoma patients from the controls with 71%
      sensitivity and 90% specificity. The test is simple to perform, reproducible, and
      probably used for detecting cholangiocarcinoma in a high-risk group or suspected
      patients.

PMID- 16793203
TI  - Cancer chemoprevention with garlic and its constituents.
AB  - Advance metastasized cancers are generally incurable; hence an effort to prolong
      the process of carcinogenesis through chemoprevention has emerged consistent with
      this notion. In recent years, a considerable attention has been placed to
      identify naturally occurring chemopreventive substances capable of inhibiting,
      retarding or reversing the process of carcinogenesis. A number of phenolic
      substances, particularly those present in dietary and medicinal plants, have been
      shown to possess substantial anticarcinogenic and antimutagenic activities.
      Epidemiological observations and laboratory studies, both in cell culture and
      animal models have indicated anticarcinogenic potential of garlic and its
      constituents, which has been traditionally used for varied human ailments around
      the world. Chemical analysis has indicated that protective effects of garlic
      appear to be related to the presence of organosulfur compounds mainly allyl
      derivatives. Several mechanisms have been presented to explain cancer
      chemopreventive effects of garlic-derived products. These include modulation in
      activity of several metabolizing enzymes that activate and detoxify carcinogens
      and inhibit DNA adduct formation, antioxidative and free radicals scavenging
      properties and regulation of cell proliferation, apoptosis and immune responses.
      Recent data show that garlic-derived products modulate cell-signaling pathways in
      a fashion that controls the unwanted proliferation of cells thereby imparting
      strong cancer chemopreventive as well as cancer therapeutic effects. This review
      discusses mechanistic basis of cancer chemopreventive effects of garlic-derived
      products, their implication in cancer management and ways and means to take these
      agents from bench to real life situations.

PMID- 16793204
TI  - Electrochemical catalytic treatment of wastewater by metal ion supported on
      cation exchange resin.
AB  - The electrochemical oxidation of phenol in synthetic wastewater and paper mill
      wastewater catalyzed by metal ion supported on cation exchange resin in suspended
      bed electrolytic reactor with graphite electrode has been investigated. The
      catalyst was characterized by SEM and XPS spectra and the effects of pH, the
      different metal ion and NaCl on the efficiency of the electrochemical oxidation
      phenol process were also studied. It was found that the catalyst containing
      Fe(3+) had the highest electrochemical catalytic activity for the electrochemical
      oxidation of phenol. When the initial concentration of phenol was 200 ppm, up to
      90% chemical oxygen demand (COD) removal was obtained in 10 min. When the
      catalyst containing Fe(3+) was used to the paper mill wastewater, it still showed
      high efficiency. The COD removal could get to 75% in 60 min.

PMID- 16793205
TI  - Study on degradation of methyl orange using pelagite as photocatalyst.
AB  - Pelagite of East Pacific Ocean as a low-price, very high reserve photocatalyst,
      has been successfully used for the first time to realize total degradation and
      decoloration of methyl orange within 120 min through photocatalysis. The
      photocatalysis and degradation performance of pelagite for methyl orange under
      the effect of various factors has been studied. Results show that pelagite has
      satisfactory photocatalysis effect in degradation of organic compounds.

PMID- 16793206
TI  - IL-8 (-251 A/T) and CXCR2 (+1208 C/T) gene polymorphisms and risk of multiple
      sclerosis in Iranian patients.
AB  - IL-8 plays important roles in CNS development, modulation of neuronal survival
      and excitability. Among IL-8 receptors, only CXCR2 is known to be present in the
      brain. The ability of individuals in producing IL-8 is partially determined by IL
      8 -251 A/T polymorphism. Therefore, the aim of the present study was to
      investigate the association between IL-8 -251 A/T and CXCR2 +1208 C/T gene
      polymorphisms and susceptibility to multiple sclerosis (MS). Two hundred and
      twenty-three MS patients and 319 healthy and ethnic matched controls were
      included in this study. IL-8 promoter (-251 A/T) and CXCR2 (+1208 C/T) gene
      polymorphisms were genotyped via allele specific PCR (AS-PCR) method. A
      significant difference was found in IL-8 -251 A/T polymorphism between MS
      patients and controls (p = 0.04). This deference was a result of a higher
      incidence of the low producer allele of IL-8 (T allele) in MS patients compared
      to controls. However, there was no significant association between different
      clinical findings (EDSS score, progression index, disease onset age, and the type
      of disease) and IL-8 -251 A/T polymorphism. Furthermore, no significant
      association existed between CXCR2 +1208 C/T polymorphism and MS susceptibility or
      different clinical parameters in patients. In summary, carriers of IL-8 -251 T
      allele may have increased susceptibility to MS because of their differences in
      neuron survival or increased chances of viral persistence compared to carriers of
      A allele.

PMID- 16793207
TI  - Trautmann's neck injury was painful after all.

PMID- 16793208
TI  - Muscle pain in myophosphorylase deficiency (McArdle's disease): the role of
      gender, genotype, and pain-related coping.
AB  - Pain characteristics were examined in 24 patients with myophosphorylase
      deficiency (McArdle's disease). Pain parameters were related to mutation analyses
      as well as psychosocial data using a pain questionnaire including an assessment
      of psychosocial distress and coping measures (Beck Depression Inventory BDI; Kiel
      Pain Inventory KPI, Multidimensional Fatique Inventory MFI). Twenty-three
      patients complained of pain, which was intermittent and exercise-induced in 15
      patients. Eight patients complained of permanent pain, which was superimposed by
      exercise-induced pain in 7 patients. Patients reported 3-7 different pain
      characters and various localisations. Patients with permanent pain were
      significantly more frequently female, experienced higher impact on general
      activities and sleep as well as higher scores on the MFI. Furthermore, these
      patients revealed higher scores regarding several psychosocial risk factors
      including avoidance behavior whereas patients with intermittent pain
      predominantly showed endurance coping. There was no correlation between age or
      disease duration, pain intensity as well as mutation type and development of
      permanent or intermittent pain. In addition, severity of the clinical phenotype
      did not correlate with ACE polymorphism. Although McArdle's disease is a muscle
      glycogenosis with marked biochemical homogeneity, the clinical presentation can
      be quite heterogeneous. A substantial number of patients revealed permanent pain
      as a major clinical symptom. As permanent pain is not related to age or disease
      duration, it might be a clinically important subgroup of McArdle's disease.
      Gender-related genetic factors as well as maladaptive pain-related coping may
      contribute to the development of such a chronic pain symptom.

PMID- 16793209
TI  - Single-agent purine analogues for the treatment of chronic lymphocytic leukaemia:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Recent trials suggest improved response rates for purine analogues
      compared to alkylator-based regimens in the treatment of B-CLL. However, none was
      able to show a survival advantage. Thus, a systematic Cochrane review may be able
      to further define the role of purine analogues in the first-line treatment of B
      CLL. METHODS: Randomized controlled trials comparing single-agent purine
      analogues with alkylator-based regimens were included. Medical databases
      (Cochrane Library, MEDLINE, EMBASE), conference proceedings and trial registers
      were searched. We included full-text and abstract publications as well as
      unpublished data. Relative risks (RR) and hazard ratios (HR) were calculated
      under a fixed-effects model, clinical and statistical heterogeneity was examined
      with sensitivity analyses and meta-regression. If applicable, numbers needed to
      treat or harm (NNT, NNH) were also determined. FINDINGS: Five trials with 1838
      randomized patients were included. Importantly, four trials had a cross-over
      design. There was a trend for improved overall survival for patients receiving
      purine analogues as initial therapy but statistical significance was just not
      reached (HR 0.89 [95% CI 0.78-1.01]). The RR for achieving an overall (RR 1.22
      [95% CI 1.13-1.31]; NNT 8 [95% CI 6-13]) and complete response (RR 1.94 [95% CI
      1.65-2.28]; NNT 6 [5-8]) was significantly improved, resulting in a longer
      progression-free survival (HR 0.70 [95% CI 0.61-0.82]). Incidence of grade III/IV
      infections (RR 1.83 [95% CI 1.30-2.58]; NNH 20 [95% CI 12.5-50]) and haemolytic
      anaemia (RR 3.36 [95% CI 1.27-8.91]; NNH 21 [95% CI 6-185]) was significantly
      higher in patients receiving purine analogues. INTERPRETATION: Despite
      significantly increased response rates and longer progression-free survival with
      purine analogues as first-line therapy, we were not able to detect a
      statistically significant improvement of overall survival compared to alkylator
      based regimens. Furthermore, the use of purine analogues augments the risk for
      grade III/IV infections and haemolytic anaemia.

PMID- 16793210
TI  - Suppression of the non-dominant motor cortex during bimanual symmetric finger
      movement: a functional magnetic resonance imaging study.
AB  - Patterns of bimanual coordination in which homologous muscles are simultaneously
      active are more stable than those in which homologous muscles are engaged in an
      alternating fashion. This may be attributable to the stronger involvement of the
      dominant motor cortex in ipsilateral hand movements via interaction with the non
      dominant motor system, known as neural crosstalk. We used functional magnetic
      resonance imaging to investigate the neural representation of the
      interhemispheric interaction during bimanual mirror movements. Thirteen right
      handed subjects completed four conditions: sequential finger tapping using the
      right and left index and middle fingers, bimanual mirror and parallel finger
      tapping. Auditory cues (3 Hz) were used to keep the tapping frequency constant.
      Task-related activation in the right primary motor cortex was significantly less
      prominent during mirror than unimanual left-handed movements. This was mirror-
      and non-dominant side-specific; parallel movements did not cause such a
      reduction, and the left primary motor cortex showed no such differential
      activation across the unimanual right, bimanual mirror, and bimanual parallel
      conditions. Reducing the contralateral innervation of the left hand may increase
      the fraction of the force command to the left hand coming from the left primary
      motor cortex, enhancing the neural crosstalk.

PMID- 16793211
TI  - A stereotaxic atlas of the brain of the naked mole-rat (Heterocephalus glaber).
AB  - The naked mole-rat (Rodentia, Bathyergidae: Heterocephalus glaber) is a strictly
      subterranean eusocial mammal. These rodents show a suite of morphological and
      physiological adaptations, including brain specializations, to this underground
      milieu that they have inhabited since the early Miocene. Recently, naked mole
      rats have received considerable attention as the longest living rodent known, and
      some of these brain specializations may be potentially important to their
      exceptional longevity. To serve as a basis for future brain studies, we have
      constructed a stereotaxic atlas of the brain of this species, labeling all major
      brain structures.

PMID- 16793212
TI  - A postulated role for transcriptional regulator LMO2 in the proliferation and
      involution of hemangioma.
AB  - Hemangiomas are common benign vascular tumors distinctive for their perinatal
      presentation, rapid growth during the first year of life and subsequent slowly
      involution. Many evidences suggest that hemangiomas are angiogenesis dependent
      entity. Research also indicated that the endothelium of hemangioma shared
      molecular phenotype with blood cells. LMO2 is a transcriptional regulator that
      play an important role in angiogenesis, hematopoiesis and oncogenesis of
      hematological tumor. It is logical to postulate that LMO2 may play a role in the
      pathogenesis, proliferating and involution of hemangioma. Therapies directed
      against LMO2 have potential importance for treatment of hemangioma because of
      hemangioma's limited localization and the fact that LMO2-associated protein
      complexes could regulate angiogenesis.

PMID- 16793213
TI  - Inflammation and atrial fibrillation: is Chlamydia pneumoniae a candidate
      pathogen of atrial fibrillation?
AB  - Atrial fibrillation is the most common arrhythmia, however, the mechanism of
      atrial fibrillation is not well explained. It has been considered that
      inflammation plays a role in atrial fibrillation, recently. Patients undergoing
      coronary artery bypass graft are at high risk for developing postoperative atrial
      fibrillation. The peak levels of C-reactive protein (CRP) were paralleled to the
      incidence of postoperative atrial fibrillation. In general population, CRP was
      also higher in patients with atrial fibrillation than in control people.
      Persistent atrial fibrillation patients had a higher CRP level than paroxysmal
      atrial fibrillation patients. CRP was not only associated with the presence of
      atrial fibrillation but may also predict patients at increased risk for future
      development of atrial fibrillation. Why inflammation markers in atrial
      fibrillation are high is a puzzling problem. We hypothesized that Chlamydia
      pneumoniae infection is a possible cause of atrial fibrillation by initiating
      inflammation response. It was demonstrated that infection of endothelial cells
      with C. pneumoniae elicited the production of Monocyte Chemoattractant Protein-1,
      interleukin-1, interleukin-8, interleukin-18, tumor necrosis factor, interferon
      and soluble intercellular adhesion molecule. Most of these cytokines play a
      crucial role in inflammation response that associate with the initiating and
      maintenance of atrial fibrillation. There are so many pathogens that can trigger
      inflammation. Some evidences showed that C. pneumoniae was the most likely
      pathogen of atrial fibrillation. In epidemic study, the incidence of atrial
      fibrillation increased from younger to elder and atrial fibrillation was more
      common in men than in women. C. pneumoniae has the same epidemic trend as the
      incidence of atrial fibrillation. Hypertension, myocardial infarction and reduced
      lung function are predictors of atrial fibrillation. C. pneumoniae infection is
      high in the patients with the above diseases. C. pneumoniae was found in
      endomyocardial biopsy samples, which supported C. pneumoniae was the candidate
      pathogen, too. Chlamydia infection can cause myocardial interstitial fibrosis and
      inflammation cells infiltration. The pathology characters of C. pneumoniae
      infection are similar to that found in atrial fibrillation. Seroepidemic study
      should be carried out to evaluate if there is relationship between C. pneumoniae
      and atrial fibrillation. If the hypothesis is confirmed, macrocyclic lactone
      antibiotics may be used to eliminate the pathogen. It will be a new target point
      to treat atrial fibrillation.

PMID- 16793214
TI  - Feasibility of preoperative combined radiation therapy and chemotherapy with 5
      fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma:
      The French SFRO-FFCD 97-04 Phase II trial.
AB  - PURPOSE: More than 80% of patients who undergo a potentially curative resection
      for pancreatic cancer develop local or distant recurrence. Neoadjuvant
      chemoradiotherapy might offer potential benefits regarding local and systemic
      control and survival. This multi-institutional Phase II trial explored the
      feasibility of preoperative chemoradiation in this situation. METHODS AND
      MATERIALS: Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks),
      and chemotherapy with 5-fluorouracil (300 mg/m(2)/day, 5 days/week, 5 consecutive
      weeks) and cisplatin (20 mg/m(2)/day, Days 1-5 and 29-33), followed by surgical
      resection of the pancreatic tumor in patients without progression. RESULTS: A
      total of 41 patients were enrolled. Of these, 38 (93%) received > or =47 Gy; 30
      patients (73%) received > or =75% of the prescribed doses of chemotherapy.
      Surgical resection was performed in 26 patients (63%). Because of local or
      metastatic progression, 5 patients (12%) did not undergo surgery and 10 underwent
      surgery without resection of the pancreatic tumor. Operative mortality was 2.8%.
      Among 40 evaluable patients, 27 were successfully treated (67.5%; 95% CI, 50.9
      81.4%). CONCLUSIONS: Pancreatic cancer is chemo-radiosensitive. The proposed pre
      operative scheme is feasible, does not prevent successful surgery, and must be
      tested on a Phase III setting. Yet, the large proportion of tumor progression
      during and after chemoradiation justifies the use of more efficient drugs such as
      Gemcitabine, and optimized radiotherapy including new techniques such as
      intensity-modulated radiation therapy.

PMID- 16793215
TI  - Geometric shifting of the porta hepatis during posthepatectomy radiotherapy for
      biliary tract cancer.
AB  - PURPOSE: To evaluate geometric shifting of the porta hepatis induced by liver
      regeneration during radiotherapy (RT) after partial hepatectomy for biliary tract
      cancer. METHODS AND MATERIALS: Between August 2004 and August 2005, the study
      enrolled 10 biliary tract cancer patients who underwent hemihepatectomy or more
      extensive surgery and were scheduled to receive postoperative RT. All patients
      received 4500 cGy RT in 25 fractions with concurrent 5-fluorouracil. Before RT
      and in the third and fifth weeks during RT, the liver volume was determined using
      CT, and geometric location of the porta hepatis was determined using a
      conventional simulator. RESULTS: The liver volume increase during RT was 246.6 +/
      118.2 cm(3). The overall actual shifting length of the porta hepatis was 9.8 +/-
      2.5 mm, with right and left hepatectomy causing a 10.1 +/- 1.7 mm shift to the
      right or 9.2 +/- 4.3 mm shift to the left, respectively. The actual shifting
      length of the porta hepatis was proportional to the increase in liver volume
      during RT (r = 0.742, p = 0.014). CONCLUSION: The results of this study have
      demonstrated that the porta hepatis can be shifted by liver regeneration after
      partial hepatectomy. We recommend an additional RT margin or adaptive RT (repeat
      planning at several intervals during the treatment course) to avoid exclusion of
      the porta hepatis from the RT target volume after partial hepatectomy for biliary
      tract cancer.

PMID- 16793216
TI  - Six fractions per week of external beam radiotherapy and high-dose-rate
      brachytherapy for carcinoma of the uterine cervix: A phase I/II study.
AB  - PURPOSE: This study evaluated the treatment results of external beam radiotherapy
      administered in six fractions per week and high-dose-rate (HDR) brachytherapy for
      the treatment of cervical cancer. METHODS AND MATERIALS: From July 2000 to July
      2003, 43 patients were enrolled in this study. The patients received 45 Gy from a
      10-MV photon beam using four-field box or anterior-posterior beams. Parametrial
      regions and the pelvic side walls were boosted with up to 50.4 Gy using a midline
      block. The daily fraction dose was 1.8 Gy administered in six-weekly fractions,
      from Monday to Saturday. HDR brachytherapy was also delivered at doses of 24 Gy
      to point A in six fractions twice a week. The median follow-up time was 37 months
      (range, 9-60 months). RESULTS: The median overall treatment time was 51 days for
      all patients (range, 44-62 days). Thirty-four patients (79.1%) achieved complete
      remission and 8 (18.6%) achieved partial remission after radiotherapy.
      Locoregional recurrence occurred in 5 patients (11.6%), and a distant metastasis
      was encountered in 6 patients (13.9%). The 3-year overall survival, locoregional,
      and distant metastasis-free survival rates were 74.7%, 87.8%, and 84.7%,
      respectively. Grade 2 and 3 late rectal complications were encountered in 3
      (6.5%) and 1 (2.2%), respectively. There were no Grade 3 late bladder
      complications. CONCLUSIONS: Six fractions per week of external beam radiotherapy
      and HDR brachytherapy is an effective treatment for patients with a carcinoma of
      the uterine cervix and can be used as a possible alternative to concomitant
      chemoradiotherapy in elderly patients or in patients with co-morbidity.

PMID- 16793217
TI  - Molluscicidal activity against Bulinus truncatus of Croton campestris.
AB  - The bark of Croton campestris provided three furano-clerodane named,
      respectively, velamone, velamolone acetate and velamolone. Fractions containing
      these diterpenoids were investigated for their molluscicidal activity against
      Bulinus truncatus, one of the aquatic snail vectors of schistosomiasis. A
      dichloromethanic extract of root barks, rich in furano-clerodane and
      molluscicidal at 20ppm was promising as natural molluscicide. Enriched fraction
      with velamone gave 80% mortality from 25ppm, while its LD(100) was at 50ppm. The
      LD(80) was ca. at 45ppm, while LD(100) was at 60ppm for the enriched fraction
      containing velamolone acetate. The velamolone-enriched fraction was less
      efficient and gave a mortality of 90% at 90ppm. The pure compounds, velamone and
      velamolone acetate were active at 100% at 3 and 6ppm, respectively. Velamolone
      showed a molluscicidal activity at 20ppm.

PMID- 16793218
TI  - Inhibition of clotrimazole-resistant Candida albicans by some endemic Sideritis
      species from Turkey.
AB  - The anticandidal activity of the methanol extracts of seven endemic Sideritis
      species were evaluated at 30 mg/ml concentration against clotrimazole-resistant
      Candida albicans.

PMID- 16793219
TI  - Molecular order in concurrent response sequences.
AB  - We studied the order of emission of concurrently reinforced free-operant two
      response sequences such as left-left (LL) and left-right (LR). The end of each
      sequence was demarcated by stimulus change. The use of demarcated sequences of
      responses, as opposed to individual responses, provides an expanded set of
      distinct, temporally ordered behaviour pairings to investigate (e.g., LL followed
      by LL, LL followed by LR, etc.); it is as well a real-life analogue. A sequential
      analysis of new and existing rat and pigeon data revealed patterns in both
      overall and post-reinforcer-only sequence emission order. These patterns were
      consistent across species and individuals, and they followed higher-order
      organising principles. We describe sequence non-repetition, last-response
      repetition, and the proportion and post-reinforcer effects, and relate them to
      existing molar and molecular behaviour principles. Beyond their immediate
      implications, our results illustrate the value of sequential analysis as a tool
      for the investigation of molar-molecular behavioural relations.

PMID- 16793220
TI  - Opportunities in Hispanic drug abuse research.

PMID- 16793222
TI  - Hispanic drug abuse research: challenges and opportunities.

PMID- 16793221
TI  - A randomized controlled trial of interim methadone maintenance: 10-Month follow
      up.
AB  - This study compares interim maintenance (IM) to a waiting list condition at an
      opioid treatment program (OTP). As defined by US federal regulations, IM provides
      observed methadone dosing and emergency counseling only for a maximum of 120
      days. Three hundred and nineteen individuals enrolled on an OTP waiting list were
      randomly assigned on a 3:2 basis to either IM or waiting list control. Outcomes
      were measured at OTP entry (or at 4 months from baseline for those who did not
      enter treatment), and 6 months thereafter. At the second follow-up, 129 (64.8%)
      of the IM participants reported being enrolled in an OTP, versus 33 (27.5%) of
      the controls, p<.001. Significant treatment conditionxtime interaction effects
      occurred for heroin and cocaine use (both p's<.001) and the ASI Legal composite
      score (p<.001). Moreover, a significant difference occurred between conditions at
      the second follow-up for heroin-positive drug tests (interim 48.1% versus control
      72.3%, p=.001) but not for cocaine-positive drug tests. At 10 months after study
      enrollment, there are sustained benefits of IM as compared to waiting list in
      terms of increased treatment entry and reduced heroin use and criminal behavior.

PMID- 16793223
TI  - Gender differences in the relationship between alcohol use and anxiety symptoms
      among Nigerian college students.
AB  - Few studies have addressed the effect of gender on the relationship between
      alcohol and anxiety. Students in a Nigerian university, grouped into five
      separate categories of alcohol use completed the Zung's Self Rating Anxiety
      Scale. Although a non-linear "J shaped" relationship was found between alcohol
      use and anxiety symptoms among males, a linear relationship was found among
      females. Women tend not to share the positive effect moderate alcohol use confers
      on anxiety status. This gender difference may be an important consideration when
      planning preventive strategies for alcohol related problems in Nigerian youths.

PMID- 16793224
TI  - Identification and molecular modeling of a novel, plant-like, human purple acid
      phosphatase.
AB  - Purple acid phosphatases are a family of binuclear metallohydrolases that have
      been identified in plants, animals and fungi. Only one isoform of approximately
      35 kDa has been isolated from animals, where it is associated with bone
      resorption and microbial killing through its phosphatase activity, and hydroxyl
      radical production, respectively. Using the sensitive PSI-BLAST search method,
      sequences representing new purple acid phosphatase-like proteins have been
      identified in mammals, insects and nematodes. These new putative isoforms are
      closely related to the approximately 55 kDa purple acid phosphatase characterized
      from plants. Secondary structure prediction of the new human isoform further
      confirms its similarity to a purple acid phosphatase from the red kidney bean. A
      structural model for the human enzyme was constructed based on the red kidney
      bean purple acid phosphatase structure. This model shows that the catalytic
      centre observed in other purple acid phosphatases is also present in this new
      isoform. These observations suggest that the sequences identified in this study
      represent a novel subfamily of plant-like purple acid phosphatases in animals and
      humans.

PMID- 16793225
TI  - Identification and characterization of the telomerase reverse transcriptase of
      Bombyx mori (silkworm) and Tribolium castaneum (flour beetle).
AB  - Chromosomal ends of most eukaryotes are composed of simple telomeric repeats.
      Arthropod telomeres are generally constituted by TTAGG pentanucleotide repeats;
      however, some insect species including Drosophila melanogaster do not have
      telomeric repeats. In contrast, the domestic silkworm Bombyx mori contains TTAGG
      type telomeric repeats, but the telomerase activity has not been detected in all
      investigated tissues. To search for a cause of unusual telomere structure in
      insects, we here identified telomerase reverse transcriptase (TERT) subunit from
      the domestic silkworm B. mori and the flour beetle Tribolium castaneum. This is
      the first report of telomerase genes from arthropods. The domestic silkworm TERT
      gene (BmoTERT) and the flour beetle TERT gene (TcasTERT) both did not have the N
      terminal GQ motif. Comparison between cDNA and genomic DNA of BmoTERT revealed
      that it includes no introns. BmoTERT contains five ATG codons in its 5'UTR, which
      could reduce the translation of BmoTERT proteins. Also, Northern hybridization
      indicated that BmoTERT is transcribed at a very low level. These unique features
      of BmoTERT possibly explain the undetectable Bombyx telomerase activity.

PMID- 16793227
TI  - Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration
      in piglets.
AB  - BACKGROUND: Meconium aspiration-induced hypertensive lung injury is frequently
      associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the
      treatment of pulmonary hypertension, but its effects on the brain are poorly
      known. AIMS: The aim of this study was to determine the effects of iNO treatment
      on the neuronal tissue after meconium aspiration. STUDY DESIGN: 71 anesthetized,
      catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five
      piglets were instilled with a bolus of human meconium intratracheally and 36
      piglets with saline instillation served as controls. Nineteen meconium piglets
      and 17 control piglets were continuously treated with 20 ppm of iNO, started at
      30 min after the insult. The extent of neuronal injury was analysed
      histologically, and the levels of brain tissue lipid peroxidation products,
      reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were
      analysed as indicators of oxidative stress. RESULTS: iNO treatment diminished the
      pulmonary hypertensive response caused by meconium aspiration, but did not change
      systemic or carotid hemodynamics. NO administration was associated with reduced
      neuronal injury and diminished amount of oxidized DNA in the hippocampus of the
      meconium piglets. Further, iNO treatment was associated with decreased level of
      GSH in the cortex, but no change in lipid peroxidation production or
      myeloperoxidase activity was detected in any of the studied brain areas.
      CONCLUSIONS: Our results suggest that iNO treatment may inhibit DNA oxidation and
      neuronal injury in the hippocampus, associated with newborn meconium aspiration.

PMID- 16793226
TI  - Isolation and identification of Taylorella asinigenitalis from the genital tract
      of a stallion, first case of a natural infection.
AB  - Contagious equine metritis (CEM), caused by Taylorella equigenitalis, is a widely
      known highly contagious genital equine disease that is transmitted venereally. A
      new bacterium, Taylorella asinigenitalis resembling T. equigenitalis was recently
      isolated from three American donkey jacks, at routine testing for CEM. The
      purpose of this study was to identify and characterize a strain of Taylorella sp.
      from the genital tract of a stallion. Swab samples for culture of T.
      equigenitalis were taken from urethral fossa, urethra and penile sheath of a 3
      year-old stallion of the Ardennes breed when it was routinely tested for CEM. A
      small Gram-negative rod was isolated, but the colony appearance, the slow growth
      rate and the results in the API ZYM test differed slightly from those of T.
      equigenitalis. Sequencing of the 16S rRNA gene was therefore performed and
      phylogenetic analysis demonstrated that the sequence of the strain Bd 3751/05
      represents T. asinigenitalis and that the strain is identical with the
      Californian asinine strain UCD-1T (ATCC 700933T). The T. asinigenitalis strain
      had a low MIC of gentamicin (MIC<or=1 microg/ml) but a high MIC of streptomycin
      (MIC>16 microg/ml). Taylorella asinigenitalis has thus for the first time been
      isolated from the genital tract of a stallion with a natural infection. To
      determine the pathogenicity of T. asinigenitalis it will be important to conduct
      further experimental studies. Sequence analysis of 16S rRNA genes was shown to be
      a reliable tool for differentiation of T. asinigenitalis from T. equigenitalis as
      well as for identification of these species.

PMID- 16793228
TI  - Toxicological analysis in rats subjected to heroin and morphine overdose.
AB  - In heroin overdose deaths the blood morphine concentration varies substantially.
      To explore possible pharmacokinetic explanations for variable sensitivity to
      opiate toxicity we studied mortality and drug concentrations in male Sprague
      Dawley rats. Groups of rats were injected intravenously (i.v.) with heroin, 21.5
      mg/kg, or morphine, 223 mg/kg, causing a 60-80% mortality among drug-naive rats.
      Additional groups of rats were pre-treated with morphine for 14 days, with or
      without 1 week of subsequent abstinence. Brain, lung and blood samples were
      analyzed for 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6
      glucuronide. i.v. morphine administration to drug-naive rats resulted in both
      rapid and delayed deaths. The brain morphine concentration conformed to an
      exponential elimination curve in all samples, ruling out accumulation of morphine
      as an explanation for delayed deaths. This study found no support for formation
      of toxic concentration of morphine-6-glucuronide. Spontaneous death among both
      heroin and morphine rats occurred at fairly uniform brain morphine
      concentrations. Morphine pre-treatment significantly reduced mortality upon i.v.
      morphine injection, but the protective effect was less evident upon i.v. heroin
      challenge. The morphine pre-treatment still afforded some protection after 1 week
      of abstinence among rats receiving i.v. morphine, whereas rats given i.v. heroin
      showed similar death rate as drug-naive rats.

PMID- 16793229
TI  - Changes in chromosome structure, mitotic activity and nuclear DNA content from
      cells of Allium Test induced by bark water extract of Uncaria tomentosa (Willd.)
      DC.
AB  - The influence of water extract of Uncaria tomentosa (Willd.) DC bark on the
      meristematic cells of the root tips of Allium cepa L., e.g. cells of Allium Test,
      was investigated. The experiment was carried out in two variants: (1) continuous
      incubation at different concentrations (2, 4, 8 and 16 mg/ml) of the extract for
      3, 6, 12, 24, 48 and 72h; and (2) 24-h incubation in three concentrations of the
      extract (4, 8 or 16 mg/ml), followed by post-incubation in distilled water for 3,
      6, 12, 24 and 48h. During the continuous incubation, the mitotic activity was
      reduced (2 and 4 mg/ml) or totally inhibited (8 and 16 mg/ml), depending on the
      concentration of the extract. All the concentrations resulted in gradual
      reduction of the mitotic activity. In the concentration of 2 mg/ml, the mitotic
      activity reached its lowest value after 12h (2 mg/ml) and after 24h in 4 mg/ml,
      followed by spontaneous intensification of divisions during further incubation.
      Instead, in higher concentrations of the extracts (8 and 16 mg/ml), the mitotic
      activity was totally inhibited within 24h and did not resume even after 72h.
      Incubation caused changes in the phase index, mainly as an increase in the number
      of prophases. After 24h of incubation, in all phases, condensation and
      contraction of chromosomes were observed. During post-incubation, divisions
      resumed in all concentrations, reaching even higher values than the control.
      Cytometric analysis showed that the extract caused inhibition of the cell cycle
      at the border between gap(2) and beginning of mitosis (G(2)/M).

PMID- 16793230
TI  - Case histories in forensic medicine.
AB  - Case histories make up a great part of publications in forensic medicine,
      especially forensic pathology, although considered low on the hierarchy of
      evidence based medicine because of its inherent anecdotal nature. Meanwhile some
      journals exclude case histories categorically from publication. The boom of case
      histories in forensic medicine has not only opportunity reasons (easily [even
      mental] and cheap to do) but also structural reasons: due to its tasks in case
      work many items of forensic medicine can not be simulated experimentally for
      ethical reasons (violent death, traumatic injuries, sexual assault, poisonings,
      influence of alcohol and drugs on driving ability and legal responsibility,
      medical malpractice, adverse events during medical care). In these fields the
      role of case histories is mainly the augmentation of experience based knowledge.
      However, quality aspects have to be considered and case histories should be the
      basis for systematic or hypothesis based research.

PMID- 16793231
TI  - Demands on scientific studies in different fields of forensic medicine and
      forensic sciences. Traffic medicine--impaired driver: alcohol, drugs, diseases.
AB  - Since human performance is a key factor in crash causation detailed knowledge of
      the involvement of alcohol, drugs and diseases is of fundamental interest for
      road safety. To better understand the effect of these influencing factors it is
      important to use a combination of witness observations and a range of
      experimental and epidemiological studies. Epidemiological approaches to research
      such as road-side-surveys, case-control-studies, culpability analysis, pharmaco
      epidemiological studies are usually seen as being able to provide the best
      answers. This article discusses the relative merits of experimental and
      epidemiological approaches.

PMID- 16793232
TI  - Family clustering in Sardinian longevity: a genealogical approach.
AB  - This paper aims to discuss the validation and family determinants affecting the
      longevity of Sardinian centenarians, using a genealogical approach. This
      preliminary study presents the first results of a genealogical tree
      reconstruction of selected centenarians aged 105 and over, from certain areas.
      These are mostly situated in the province of Nuoro, an area with the highest rate
      of centenarians and where the female-to-male sex ratio tends to be male-biased.
      An accurate centenarian age validation was performed that required a meticulous
      examination of numerous civil status records and parish registers. An important
      finding was that longevity occurs among the ascendants of a particular branch of
      the family. The data used are still provisional but, should it apply to other
      validated cases, it would provide empirical evidence of a genetic component in
      longevity. A more thorough examination of the data available may yield deeper
      insights into the role played by endogamy and consanguinity.

PMID- 16793233
TI  - Esophageal injuries: spectrum of multidetector row CT findings.
AB  - BACKGROUND: Aim of this study is to illustrate the multidetector row computed
      tomographic findings related to oesophageal injuries and their significance for
      therapeutic decisions. METHOD: From April 2002 to April 2005 we studied 16
      patients with suspected oesophageal injury. Ten patients underwent standard chest
      radiograph, while five patients with suspected foreign body ingestion were
      submitted to cervical plain film and gastrografin swallow study. All 16 patients
      underwent multidetector row CT examination. RESULTS: In six patients with
      cervical, thoracic and abdominal trauma, CT showed the presence of thoracic
      traumatic lesions and findings suggestive of perforation of the oesophagus. In
      five patients with foreign body ingestion cervical radiography was positive in
      only one case, while CT showed the presence of a foreign body in all cases. In
      three patients with post-intubation complications, CT showed the presence of
      perioesophageal fluid collection containing small gas bubbles in two cases and an
      oesophageal-aortic fistula in one case. In the remaining two patients with
      suspected spontaneous oesophageal perforation, CT demonstrated an oesophageal
      wall oedema and thickening in one case, and oesophageal fluid distension with
      perioesophageal small bubbles gas and fluid in the second case. CONCLUSION:
      Oesophageal injuries, when complicated with perforation, constitute a life
      threatening condition. Knowledge of the CT signs of oesophageal injuries has
      important implications for the role of imaging at the time of initial diagnosis.

PMID- 16793234
TI  - Analysis of denitrification genes and comparison of nosZ, cnorB and 16S rDNA from
      culturable denitrifying bacteria in potato cropping systems.
AB  - Bacterial denitrification in agricultural soils is a major source of nitrous
      oxide, a potent greenhouse gas. This study examined the culturable bacterial
      population of denitrifiers in arable field soils in potato (Solanum tuberosum L.)
      production and denitrification genes (nir, nor and nos) and 16S rDNA in those
      isolates. Enrichments for culturable denitrifiers yielded 31 diverse isolates
      that were then analysed for denitrification genes. The nitrous oxide reductase
      (nosZ) gene was found in all isolates. The majority of isolates ( approximately
      90%) contained the cnorB nitric oxide reductase gene, with the remainder
      containing the qnorB gene. Nitrite reductase genes (nirS and nirK) were
      amplifiable from most of the isolates, and were segregated between species
      similar to previously isolated denitrifiers. Isolated strains were preliminarily
      identified using fatty acid methyl ester analysis and further identified using
      16S rDNA sequencing. The majority of isolates (21) were classified as Pseudomonas
      sp., with smaller groups of isolates being most similar to Bosea spp. (4),
      Achromobacter spp. (4) and two isolates closely related to Sinorhizobium/Ensifer
      spp. Phylogenetic trees were compared among nosZ, cnorB and 16S rDNA genes for a
      subset of Pseudomonas strains. The trees were mostly congruent, but some
      Pseudomonas sp. isolates grouped differently depending on the gene analysed,
      indicating potential horizontal gene transfer of denitrification genes. Although
      Bosea spp. are known denitrifiers, to the best of our knowledge this is the first
      report of isolation and sequencing of denitrification genes from this bacterial
      genus.

PMID- 16793235
TI  - Active immunization against ghrelin decreases weight gain and alters plasma
      concentrations of growth hormone in growing pigs.
AB  - Ghrelin has been implicated in the control of food intake and in the long-term
      regulation of body weight. We theorize that preventing the ability of ghrelin to
      interact with its receptors, would eventually lead to decreased appetite and
      thereby decrease body weight gain. To test our hypothesis, pigs were actively
      immunized against ghrelin. Ghrelin((1-10)) was conjugated to BSA and emulsified
      in Freund's incomplete adjuvant and diethylaminoethyl-dextran. Primary
      immunization was given at 19 weeks of age (WOA), with booster immunizations given
      20 and 40 days after primary immunization. Body weight (BW) and plasma samples
      were collected weekly beginning at 19 WOA, and feed intake was measured daily.
      Fourteen days after primary immunization, the percentage of bound (125)I-ghrelin
      in plasma from immunized pigs was increased compared with control animals
      (P<0.001). Voluntary feed intake was decreased more than 15% in animals that were
      actively immunized against ghrelin compared with controls. By the end of the
      experiment, immunized pigs weighed 10% less than control animals (P<0.1).
      Concentrations of GH were increased (P<0.05) in immunized pigs. Apoptosis was not
      observed in post-mortem samples obtained from the fundic region of the stomach.
      Our observations suggest that immunization against ghrelin induces mild anorexia.
      This procedure could potentially be used as a treatment to control caloric intake
      and obesity.

PMID- 16793236
TI  - Sonographically guided mammotome excision of ducts in the diagnosis and
      management of single duct nipple discharge.
AB  - AIM: To describe our experience in the use of ultrasound guided mammotome in the
      diagnosis and management of single duct nipple discharge. METHODS: Patients for
      whom surgical excision of the single duct had been advised for single duct nipple
      discharge were offered ultrasound guided mammotome excision of the duct as an
      alternative to surgical excision. The procedure was performed in the breast
      clinic by a surgeon or a breast clinician who had interventional ultrasound
      skills. RESULTS: Seventy-seven patients had 81 procedures. Follow-up at a mean
      time of 16 months revealed resolution of the presenting problematic discharge in
      95% of patients. Nipple discharge recurred in four patients. Two patients had
      microdochectomy and two had a repeat mammotome for recurrence of symptoms.
      Complications were mild and infrequent. CONCLUSION: Ultrasound guided mammotome
      excision is a new tool in the work up and management of single duct nipple
      discharge. It can be performed under local anaesthetic by a surgeon/breast
      clinician or radiologist with interventional ultrasound skills. It has the
      potential to replace surgical excision (microdochectomy) as a treatment for
      nipple discharge.

PMID- 16793237
TI  - Prospective evaluation of quality of surgery in soft tissue sarcoma.
AB  - BACKGROUND: Prospective application of the French Sarcoma Group (FSG) method of
      surgery reporting in soft tissue sarcoma (STS) in a single centre. METHODS:
      Patients with primary STS of the extremities or trunk wall consecutively operated
      at the same institution from January 1996 to December 2002 were evaluated for
      local recurrence (LR). There were 205 patients, with AJCC/UICC stages III and IV
      in 51% of cases. Resection types according to FSG were R0 in 147, R1 in 53 and R2
      in five cases. Radiotherapy was delivered in 163 patients and chemotherapy in
      103. Multivariate analysis was performed. Overall five-year survival was 75%.
      Median follow-up for surviving patients was 53 months. RESULTS: Actuarial five
      year LR incidence was 13% in 200 patients with gross resection (R0+R1), it was 7%
      in R0 and 30% in R1 patients (p<0.0001). At univariate analysis, significant
      prognosticators for LR were age, histotype, tumour invasion, grade and resection
      type R. At multivariate analysis, resection R1 (relative risk (RR) 4.3, p=0.001)
      and grade 3 (RR 3.9, p=0.013) independently predicted LR. Combining these two
      variables produced three prognostic groups for LR: group 0 (no factor, n=70),
      group 1 (one factor, n=94) and group 2 (two factors, n=36) with five-year LR of
      4%, 12% and 39%, respectively (p=6.4x10(-7)). CONCLUSION: This first prospective
      evaluation of surgery reporting in STS evidences a fourfold, highly
      discriminating difference in LR between resections R0 and R1.

PMID- 16793238
TI  - Antipsychotic medication and cognitive function in schizophrenia.
AB  - Antipsychotic polypharmacy and excessive dosing still prevail worldwide in the
      treatment of schizophrenia, while their possible association with cognitive
      function has not well been examined. We examined whether the "non-standard" use
      of antipsychotics (defined as antipsychotic polypharmacy or dosage >1,000 mg/day
      of chlorpromazine equivalents) is associated with cognitive function.
      Furthermore, we compared cognitive function between patients taking only atypical
      antipsychotics and those taking only conventionals. Neurocognitive functions were
      assessed in 67 patients with chronic schizophrenia and 92 controls using the
      Wechsler Memory Scale-Revised (WMS-R), the Wechsler Adult Intelligence Scale
      Revised (WAIS-R), the Wisconsin Card Sorting Test (WCST), and the Advanced Trail
      Making Test (ATMT). Patients showed markedly poorer performance than controls on
      all these tests. Patients on non-standard antipsychotic medication demonstrated
      poorer performance than those on standard medication on visual memory, delayed
      recall, performance IQ, and executive function. Patients taking atypical
      antipsychotics showed better performance than those taking conventionals on
      visual memory, delayed recall, and executive function. Clinical characteristics
      such as duration of medication, number of hospitalizations, and concomitant
      antiparkinsonian drugs were different between the treatment groups (both
      dichotomies of standard/non-standard and conventional/atypical). These results
      provide evidence for an association between antipsychotic medication and
      cognitive function. This association between antipsychotic medication and
      cognitive function may be due to differential illness severity (e.g., non
      standard treatment for severely ill patients who have severe cognitive
      impairment). Alternatively, poorer cognitive function may be due in part to
      polypharmacy or excessive dosing. Further investigations are required to draw any
      conclusions.

PMID- 16793239
TI  - Reduced anterior internal capsule and thalamic volumes in first-episode
      psychosis.
AB  - BACKGROUND: The thalamus is the gateway for sensory and motor information en
      route to the cortex. Information is processed via thalamocortical and
      corticothalamic pathways coursing through the internal capsules. In this study,
      we investigated the relationship between the anterior limb of the internal
      capsule, posterior limb of the internal capsule, and thalamus in first-episode
      psychosis (FEP). METHODS: Twenty-nine FEP subjects (26 DSM-IV schizophrenia, 2
      schizoaffective disorder, 1 psychosis not otherwise specified) and 22 healthy
      volunteers participated in this study. Anterior limb of the internal capsule
      (AIC), posterior limb of the internal capsule (PIC), and the thalamus volumes
      were manually determined from MRI scans. RESULTS: FEP subjects had reduced AIC
      volumes (F(1,45)=6.18, p=0.017) and thalamic volumes (F(1,45)=8.00, p=0.007)
      compared to healthy volunteers. PIC volumes did not differ. Significant
      correlations between AIC volumes and thalamic volumes were observed in subjects
      with FEP, but not in healthy volunteers. Negative relationships between thalamic
      volumes and symptom severity were also observed. CONCLUSIONS: The AIC and
      thalamic volumes were reduced in subjects with FEP compared to healthy
      volunteers. Abnormalities in thalamocortical and orticothalamic pathways may
      contribute to functional disruption of neural circuits in psychosis.

PMID- 16793240
TI  - Visuospatial working memory deficits in adolescent onset schizophrenia.
AB  - This study determines that visuospatial working memory (VSWM) deficits are
      evident in adolescent-onset schizophrenia, while the spatial strategy and spatial
      span components of VSWM are spared. These findings imply that frontal-striatal
      parietal neural networks are dysfunctional in adolescent-onset schizophrenia,
      while mid-dorsolateral and ventrolateral PFC functions remain intact: the current
      conceptualisation of schizophrenia as a progressive neurodevelopmental disorder
      is consistent with these results.

PMID- 16793241
TI  - Id3 is important for proliferation and differentiation of the hepatoblasts during
      the chick liver development.
AB  - The specified hepatic endoderm (hepatoblasts), the bipotential progenitor for
      hepatocytes and bile duct epithelial cells, proliferates during the primordial
      stages of liver development. Despite extensive studies, the mechanism that
      regulates proliferation of bipotential hepatoblasts is not fully understood. Here
      we show that Id3, a negative regulator of helix-loop-helix transcription factors,
      is an important regulator of hepatoblast proliferation in the developing chick
      liver. Id3 was expressed in hepatoblasts at early developmental stages (stages 12
      29) but not in hepatocytes at later developmental stages (stage 34 onwards).
      Depletion of Id3 in hepatoblasts by siRNA results in failure of cell
      proliferation, but is not associated with either cell death or failure of
      expression of Hhex and Fibrinogen, the earliest hepatoblast markers. These
      observations suggest that at early developmental stages, Id3 functions as a
      positive regulator of hepatoblast proliferation, independent of cell death or
      maintenance of the non-terminally differentiated state. Interestingly at later
      developmental stages, the expression pattern of Id3 is complementary to that of
      Albumin, a marker of mature hepatocytes. Overexpression of Id3 in liver explants
      delayed the initiation of Albumin expression. Taken together, our observations
      show that Id3 is not only a positive regulator of hepatoblast proliferation, but
      also an inhibitor of their differentiation into hepatocytes in the developing
      chick liver.

PMID- 16793242
TI  - Mummy encodes an UDP-N-acetylglucosamine-dipohosphorylase and is required during
      Drosophila dorsal closure and nervous system development.
AB  - Throughout development cell-cell interactions are of pivotal importance. Cells
      bind to each other or share information via secreted signaling molecules. To a
      large degree, these processes are modulated by post-translational modifications
      of membrane proteins. Glycan-chains are frequently added to membrane proteins and
      assist their exact function at the cell surface. In addition, the glycosylation
      pathway is required to generate GPI-linkage in the endoplasmatic reticulum. Here,
      we describe the analysis of the cabrio/mummy gene, which encodes an UDP-N
      acetylglucosamine diphosphorylase. This is a well-conserved and central enzyme in
      the glycosylation pathway. As expected from this central role in glycosylation,
      cabrio/mummy mutants show many phenotypic traits ranging from CNS fasciculation
      defects to defects in dorsal closure and eye development. These phenotypes
      correlate well with specific glycosylation and GPI-anchorage defects in mummy
      mutants.

PMID- 16793243
TI  - [Hemophagocytic syndrome occurring in polyarticular juvenile arthritis treated by
      salazopyrine].

PMID- 16793244
TI  - [Lambert-Eaton myastenic syndrome revealing neuroblastoma in 2 children].
AB  - Lambert-Eaton myasthenic syndrome is a paraneoplasic syndrome which can reveal a
      primitive tumor. Frequently, the first diagnosis is myasthenia gravis. This
      disease is extremely rare in children. Only 10 cases have been reported in the
      last 35 years. We report 2 new observations occurring in very young patients,
      aged 2 and 3 years, with a ganglioneurobastoma as primitive tumor.

PMID- 16793245
TI  - Influence of Verapamil and Cyclosporin A on bile acid metabolism and transport in
      rat liver slices.
AB  - Verapamil (V) is a specific inhibitor of the P-glycoprotein (mdr1) in the
      hepatocyte canalicular membrane. Cyclosporin A (CsA) as an essential
      immunosuppressive drug has potentially cholestatic adverse effects on the liver,
      but increases the expression of mdr1. In precision-cut liver slices from 34- to
      40-day-old male Wistar rats 26 individual free and conjugated bile acids (BAs) as
      markers of hepatic transport and synthesis function were analysed after 4 h
      incubation with V (100 microM) or CsA (5 microM) in Krebs-Henseleit buffer. Some
      slices were loaded with cholic acid (CA 5 microM) or tauro-ursodeoxycholic acid
      (T-UDCA 5 microM) to investigate the V and CsA effects under conditions of BA
      supplementation. BAs were determined in tissue and medium by HPLC with postcolumn
      derivatisation and fluorescence detection. V and CsA, influencing different
      targets in BA transport, enhanced slice concentrations of T- and glyco- (G-)
      conjugated CA only when exogenous CA was given additionally. This BA accumulation
      in tissue is more reflected at decreased medium concentrations of these BAs after
      V and CsA incubations. Both V and CsA also inhibited CA uptake into the slices.
      The acidic chenodeoxycholic acid (CDCA) synthesis pathway is disturbed: T- and G
      CDCA concentrations are diminished in slices and medium after V and CsA
      incubations. T-UDCA plus V or CsA enhanced not only its own slice concentration
      but also the concentration of the trihydroxylated tauro-muricholic acid (T-beta
      MCA), reflecting the conversion of the accumulated dihydroxylated T-UDCA into the
      T-beta-MCA. The similar effects of V and CsA on BA transport and metabolism can
      be explained by mdr1 mediated disturbances of cellular ATP transport rather than
      by inhibition of individual BA transporters.

PMID- 16793246
TI  - Effects of rutin and quercetin on monooxygenase activities in experimental
      influenza virus infection.
AB  - The aim of this work is to study the effect of the flavonoids rutin and quercetin
      on hepatic monooxygenase activities in experimental influenza virus infection
      (EIVI). EIVI causes oxidative stress in the whole organism. This is confirmed by
      the rapidly increased concentrations of thiobarbituric reactive substances in
      influenza-infected mice: lungs - 290%; blood plasma - more than 320%; liver -
      230%; brain - 50%. Although known for their antioxidant activities, rutin and
      quercetin exhibit prooxidant effect in healthy and antioxidant activity in
      influenza-infected animals. The pretreatment with both flavonoids (20 mg/kg b.w.)
      restores oxidative damage mostly in the target organ of the infection as well as
      in the liver of all infected mice (lungs: rutin - 30%, quercetin - 40%,
      combination - 45%; liver: rutin - 12%; quercetin - 40%; combination - 50%). As
      far as EIVI causes oxidative stress, toxicosis and inhibition of the hepatic
      monooxygenase activity, it is important to study the effects of rutin and
      quercetin on these systems. Both flavonoids induce the level of cytochrome P-450
      (rutin - 13%, quercetin - 30%, combination - 22%) but inactivate NADPH-cytochrome
      c reductase, aminopyrine N-demethylase and analgin N-demethylase on the 5th day
      of EIVI. Probably, these flavonoids affect different components of the
      monooxygenase system. These effects could be explained with oxidative hepatic
      intoxication on the 5th critical day of EIVI as well as higher dose treatment.
      More data are needed on the antioxidant/prooxidant effects of rutin and
      quercetin, probably due to specific metabolic and physiological activities,
      chemical structure, etc.

PMID- 16793247
TI  - The impact of electrochemical disinfection on Escherichia coli and Legionella
      pneumophila in tap water.
AB  - In order to reduce the risks of Legionnaires' disease, caused by the bacterium
      Legionella pneumophila, disinfection of tap water systems contaminated with this
      bacterium is a necessity. This study investigates if electrochemical disinfection
      is able to eliminate such contamination. Hereto, water spiked with bacteria
      (10(4)CFU Escherichia coli or L. pneumophila/ml) was passed through an
      electrolysis cell (direct effect) or bacteria were added to tap water after
      passage through such disinfection unit (residual effect). The spiked tap water
      was completely disinfected, during passage through the electrolysis cell, even
      when only a residual free oxidant concentration of 0.07 mg/l is left (L.
      pneumophila). The residual effect leads to a complete eradication of cultivable
      E. coli, if after reaction time at least a free oxidant concentration of 0.08
      mg/l is still present. Similar conditions reduce substantially L. pneumophila,
      but a complete killing is not realised.

PMID- 16793248
TI  - PCR amplification of species specific sequences of 16S rDNA and 16S-23S rDNA
      intergenic spacer region for identification of Streptococcus phocae.
AB  - Streptococcus phocae, a bacterial pathogen of seals, could reliably be identified
      by PCR amplification using oligonucleotide primers designed according to species
      specific segments of the previously sequenced 16S rRNA gene and the 16S-23S rDNA
      intergenic spacer region of this species. The PCR mediated assay allowed an
      identification of S. phocae isolated from harbor and gray seals and from Atlantic
      salmons. No cross-reaction could be observed with 13 different other
      streptococcal species and subspecies and with Lactococcus garvieae strains
      investigated for control purposes.

PMID- 16793250
TI  - Survivability of Salmonella cells in popcorn after microwave oven and
      conventional cooking.
AB  - The survivability of Salmonella cells in popcorn preparation was determined for
      two distinct cooking methods. The first method used a standard microwave oven.
      The second method used conventional cooking in a pan. Prior to thermal processing
      in independent experiments, 12 suspensions in a range between 1x10(3) and 8x10(6)
      colony-forming units (CFU) per gram of Salmonella cells were inoculated in both
      raw microwave popcorn and conventional corn kernels. The influence of the initial
      concentration of Salmonella cells in the raw products and the lethal effects on
      Salmonella by thermal treatments for cooking were studied. Survival of Salmonella
      cells was determined in the thermally processed material by pre-enrichment and
      enrichment in selective medium, in accordance with the legislation for expanded
      cereals and cereals in flakes. Viable experimental contaminants were recovered
      from the conventionally cooked popcorn with initial inoculation concentrations of
      9x10(4)cells/g or greater. Salmonella cell viability was significantly reduced
      after microwave oven treatment, with recoveries only from initial concentrations
      of 2x10(6)cells/g or superior.

PMID- 16793249
TI  - Alternaria jesenskae sp. nov., a new species from Slovakia on Fumana procumbens
      (Cistaceae).
AB  - Alternaria jesenskae sp. nov. recovered from seeds of a shrubby perennial plant
      Fumana procumbens (Cistaceae) in Slovakia is described and illustrated. The new
      taxon can be clearly separated from the other related large-spored and filament
      beaked Alternaria species based on sequences of the ITS1, 5.8S and ITS2 region as
      well as by its distinctive morphology. Even though the molecular data have shown
      close relatedness with A. multirostrata, the new species is morphologically most
      similar to A. tomatophila distinguished primarily by the pronounced colony
      pigmentation, conidial septation and beak branching.

PMID- 16793251
TI  - Minimax regret optimization analysis for a regional solid waste management
      system.
AB  - Solid waste management (SWM) facilities are crucial for environmental management
      and public health in urban regions. Due to the waste management hierarchy, one of
      the greatest challenges that organizations face today is to figure out how to
      diversify the treatment options, increase the reliability of infrastructure
      systems, and leverage the redistribution of waste streams among incineration,
      compost, recycling, and other facilities to their competitive advantage region
      wide. Systems analysis plays an important role for regionalization assessment of
      integrated SWM systems, leading to provide decision makers with break-through
      insights and risk-informed strategies. This paper aims to apply a minimax regret
      optimization analysis for improving SWM strategies in the Lower Rio Grande Valley
      (LRGV), an economically fast growing region in the US. Based on different
      environmental, economic, legal, and social conditions, event-based simulation in
      the first stage links estimated waste streams in major cities in LRGV with
      possible solid waste management alternatives. The optimization analysis in the
      second stage emphasizes the trade-offs and associated regret evaluation with
      respect to predetermined scenarios. Such optimization analyses with multiple
      criteria have featured notable successes, either by public or private efforts, in
      diverting recyclables, green waste, yard waste, and biosolids from the municipal
      solid waste streams to upcoming waste-to-energy, composting, and recycling
      facilities. Model outputs may link prescribed regret scenarios in decision making
      with various scales of regionalization policies. The insights drawn from the
      system-oriented, forward-looking, and preventative study can eventually help
      decision-makers and stakeholders gain a scientific understanding of the
      consequences of short-term and long-term decisions relating to sustainable SWM in
      the fast-growing US-Mexico borderland.

PMID- 16793252
TI  - Nitrate and nitrite injection during municipal solid waste anaerobic
      biodegradation.
AB  - Nitrified leachate recirculation has been proposed as a promising strategy for
      sustainable landfill management. In four test reactors, nitrate or nitrite was
      added (250 mg N-NO(x)(-)L(-1)) during municipal solid waste biodegradation.
      Nitrogen-oxides reduction reactions were monitored. Denitrification was the main
      nitrogen reducing reaction observed. On one hand, during the acidogenic waste
      degradation phase, as high amounts of volatile fatty acids (VFA) were present,
      nitrogen-oxides reductions were interpreted as heterotrophic denitrifications. On
      the other hand, denitrification reactions occurring during the late methanogenic
      phase were accompanied by sulphate productions and, as VFA were not detected, it
      was probably an autotrophic reaction. Denitrification inhibition was observed
      once. Ammonium concentration increased suggesting the occurrence of a
      dissimilatory nitrate reduction to ammonium (DNRA). Statistical treatment of
      analytical data revealed that only H(2)S concentration had a significant negative
      effect on N(2) production in our system. NO production was observed once when
      nitrite was injected during the acidogenic phase resulting in a total waste
      degradation inhibition. These results indicate that the consequences of nitrified
      leachate recirculation in full-scale landfills need to be carefully examined
      especially during the acidogenic phase or in the presence of waste containing
      high quantities of sulphur.

PMID- 16793253
TI  - Measuring transient water flow in unsaturated municipal solid waste--a new
      experimental approach.
AB  - This research investigated transient water flow in unsaturated municipal solid
      waste (MSW) packed in columns using neutron scattering. The method developed was
      able to measure absolute moisture content and moisture variation in a sample of
      MSW produced in the city of Fortaleza (Brazil) during a simulated tropical rain
      event. The technique was proven to be efficient, showing that channeling flow
      accounts for most of the unsaturated flow conditions. The most important effect
      of micro-porous flow was on water accumulation and small long-term outflow.
      Furthermore, the definition of field capacity used in soil sciences does not seem
      to apply to flow in unsaturated MSW; the MSW layers kept increasing in moisture
      content long after water was allowed through. Finally, the long-term draining
      experiment demonstrated that the macro-porous matrix may not be a continuous
      medium, which makes experimental procedures that rely on matrix potential in
      specific points of the solid waste mass inaccurate.

PMID- 16793254
TI  - Amphiphilic porphyrin film on glass as a simple and selective solid-state
      chemosensor for aqueous Hg2+.
AB  - Deposition of amphiphilic porphyrin derivatives occurs spontaneously on silanised
      glass surfaces, in a controlled fashion. The resulting porphyrin films show
      appreciable fluorescence emission. This emission can be effectively quenched by
      immersion of the slides into a diluted solution of Hg(2+) (microM concentration).
      The initial intensity can be restored by washings with a solution of N,N,N',N'
      tetrakis(2-pyridilmethyl)ethylenediammine with no loss of efficiency. A
      remarkable selectivity is featured toward the detection of Hg(2+) over Cu(2+),
      Cd(2+), Pb(2+) and Zn(2+) counterparts. This protocol can be extended to a flow
      through apparatus. The presented results are of importance for the achievement of
      a solid-state chemosensor for mercuric ions, at micromolar concentration, in
      water.

PMID- 16793255
TI  - Heterogeneous optochemical VOC sensing layers selected by ESI-mass spectrometry.
AB  - Spin-coated films of 29H,31H-tetra-4-(2,4-di-tert-amylphenoxy)phthalocyanine
      (H(2)Pc) and [kappaP,mu-kappaS-(dppeS)Pt(CH(3))](2)[BF(4)](2) have been used as
      sensing layers deposited in thin film form for the detection of VOCs. The sensing
      behaviour of the blend was predicted on the basis of mass spectrometric
      determinations performed on H(2)Pc/Pt-complex solutions, by monitoring the
      formation of gas-phase ions at the electrospray interface. The addition of small
      amounts of acetonitrile produced a [M+41](+) peak whereas the addition of similar
      amounts of methanol, ethanol and isopropyl alcohol did not give the corresponding
      [M+ROH](+) species. These results were confirmed by sensing tests. A pure
      phthalocyanine optosensing element did not show relevant selectivity. Conversely,
      the heterogeneous sensing layer obtained by spin-coating deposition of a Pt
      complex/H(2)Pc blend allowed the sensing of acetonitrile vapours with respect to
      the above mentioned alcohols.

PMID- 16793256
TI  - Development and evolution of the migratory neural crest: a gene regulatory
      perspective.
AB  - The neural crest, a uniquely vertebrate characteristic, gives rise to pigment
      cells, much of the peripheral nervous system, the craniofacial skeleton, and a
      plethora of other cell types. Classical embryological studies have revealed
      important details about the migratory pathways followed by these cells, and their
      subsequent differentiation into diverse derivatives. More recently, many aspects
      of the molecular cascade of events involved in neural crest induction and
      generation of these migratory cells have been revealed. Formation of the neural
      crest appears to involve a network of interactions whereby signaling molecules
      initiate the induction and, subsequently, the establishment of the neural plate
      border, which is marked by expression of a characteristic set of transcription
      factors designated as neural plate border-specifiers. These in turn regulate
      other transcription factors termed neural crest-specifiers, which control genes
      involved in neural crest delamination, the generation of migratory cells and
      ultimately the acquisition of appropriate fates.

PMID- 16793257
TI  - Evolution of the mechanisms that establish the embryonic axes.
AB  - A long-standing debate in developmental biology concerns the extent to which
      embryos are largely 'mosaic' (cell fates are allocated by localization of
      maternal determinants that are inherited differentially) or 'regulative' (cell
      interactions determine cell fates). Generally, it has been thought that amniotes,
      especially birds and mammals, are at the extreme regulative end of the spectrum,
      whereas most invertebrates, lower chordates and anamnia are more mosaic. Various
      studies have identified additional differences, including egg size, the timing of
      zygotic transcription and the speed of development. However, new research is
      starting to reveal among the vertebrate classes an astonishing degree of
      conservation in the intercellular signalling mechanisms that regulate cell fate
      and embryonic polarity before gastrulation.

PMID- 16793258
TI  - Building the mouse gastrula: signals, asymmetry and lineages.
AB  - The mouse embryo is built by assembling the progenitors of various tissue types
      into a body plan. Early postimplantation development involves the establishment
      of anatomical asymmetries and regionalized gene expression in the conceptus, the
      specification of tissue lineages, and the coordination of cell movement for
      correct positioning of the lineage progenitors before and at gastrulation. Recent
      findings reveal that Wnt and Tgfbeta signalling function is instrumental in
      delineating the anterior-posterior embryonic axis by defining the site of
      primitive streak formation and by directing the movement of the visceral
      endoderm. These signalling activities are also required for the specification of
      anterior and posterior fates of the epiblast cells and for the induction and
      navigation of the primordial germ cells.

PMID- 16793259
TI  - The developmental migration of Plasmodium in mosquitoes.
AB  - Migration of the protozoan parasite Plasmodium through the mosquito is a complex
      and delicate process, the outcome of which determines the success of malaria
      transmission. The mosquito is not simply the vector of Plasmodium but, in terms
      of the life cycle, its definitive host: there, the parasite undergoes its sexual
      development, which results in colonization of the mosquito salivary glands. Two
      of the parasite's developmental stages in the mosquito, the ookinete and the
      sporozoite, are invasive and depend on gliding motility to access, penetrate and
      traverse their host cells. Recent advances in the field have included the
      identification of numerous Plasmodium molecules that are essential for parasite
      migration in the mosquito vector.

PMID- 16793260
TI  - Synthesis and anti-angiogenesis activity of coumarin derivatives.
AB  - A series of 7-diethylaminocoumarin compounds were synthesized and the
      cytotoxicities were tested against human umbilical vein endothelial cell (HUVEC)
      and some cancer cells. We found that the introduction of cyano groups at the 4
      position will promote the bioactivity. In particular, compounds 9 and 10 strongly
      inhibited the proliferation of various cancer cell lines, and 12 and 15 showed a
      high selectivity for HUVEC. Therefore, these coumarin molecules can be utilized
      as lead compounds to develop potential nontoxic angiogenesis inhibitors and small
      molecular ligands to target HUVEC.

PMID- 16793261
TI  - A practical and green approach toward synthesis of N3-substituted
      dihydropyrimidinones: using Aza-Michael addition reaction catalyzed by KF/Al2O3.
AB  - A simple and efficient method for the synthesis of N3-substituted 3,4
      dihydropyrimidinones by aza-Michael addition reactions of 3,4
      dihydropyrimidinones to alpha,beta-ethylenic compounds catalyzed by KF/Al(2)O(3)
      is described. The advantage of this method is high regioselectivity, high purity,
      and the use of a cheaper, milder, and efficient catalyst for the hetero-Michael
      addition reaction.

PMID- 16793262
TI  - Synthesis and anticonvulsant activity of new N-1',N-3'-disubstituted-2'H,3H,5'H
      spiro-(2-benzofuran-1,4'-imidazolidine)-2',3,5'-triones.
AB  - Thirteen new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'
      imidazolidine)-2',3,5'-triones were synthesized and their pharmacological
      activity determined with the objective to better understand their SAR for
      anticonvulsant activity. The anticonvulsant effects of these compounds were
      evaluated by standard pentylenetetrazol (scPTZ test) and maximum electroshock
      seizure (MES test) models in mice. Most of the compounds showed ability to
      protect against the pentylenetetrazol-induced convulsions. Compound 3o (the N-1'
      p-nitrophenyl, N-3'-ethyl derivative) in the N-1'-aryl, N-3'-alkyl disubstituted
      series exhibited maximum activity with ED(50) of 41.8 mg/kg in scPTZ convulsion
      model.

PMID- 16793263
TI  - An expedient synthesis of N6-substituted-5'-modified adenosines.
AB  - Herein we report a short and efficient synthesis of N(6)-substituted 5'-modified
      adenosines, which was achieved in four steps from 2',3',5'-tris-O-(tert
      butyldimethylsilyl)inosine.

PMID- 16793264
TI  - Potent 4-amino-5-azaindole factor VIIa inhibitors.
AB  - The 4-amino-5-azaindole as an amidino-benzimidazole replacement is described. A
      series of potent and selective analogs were discovered and showed desirable ex
      vivo efficacy as measured by PT.

PMID- 16793265
TI  - Two novel immunosuppressive pregnane glycosides from the roots of Stephanotis
      mucronata.
AB  - Two novel pregnane glycosides, together with one new aglycone, were isolated from
      the roots of Stephanotis mucronata. Their structures were determined by means of
      chemical evidence and extensive spectroscopic methods including 1D and 2D NMR.
      The two pregnane glycosides displayed significant immunosuppressive activities in
      vitro.

PMID- 16793266
TI  - Synthesis and biological activity of amide derivatives of nimbolide.
AB  - Nimbolide (1), a limonoid isolated from Azadirachta indica, is the chief
      cytotoxic principle in Neem leaves extract. Using nimbolide as a lead compound
      for anti-cancer analogue design, a series of nimbolide derivatives have been
      synthesized and evaluated for in vitro cytotoxic activity against a panel of
      human cancer cell lines. Out of 10 compounds screened 2g, 2h and 2i showed potent
      activity.

PMID- 16793267
TI  - Synthesis and evaluation of (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones
      as Kv1.5 channel blockers for the treatment of atrial fibrillation.
AB  - A series of novel (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones were
      prepared and examined for utility as Kv1.5 channel blockers for the treatment of
      atrial fibrillation.

PMID- 16793268
TI  - Muscle slowness in a family with nemaline myopathy.
AB  - All patients of a large family with nemaline myopathy complained of slowness in
      movement. We confirmed this clinical complaint physiologically by showing lower
      contractile speed in quadriceps muscle. Electrically evoked contractions of the
      quadriceps muscle elicited a lower rate of relaxation and a tendency for slower
      torque generation. Here, we demonstrate for the first time slow muscle
      characteristics as a physiological correlate for the clinical complaint of
      slowness.

PMID- 16793269
TI  - A systematic review of diagnostic studies in myasthenia gravis.
AB  - We performed a systematic review to identify studies that reported the accuracy
      of tests for the diagnosis of myasthenia gravis. We identified 20 studies of
      reasonable, although variable, methodological quality upon which to base
      estimates of the accuracy of the ice test, rest test, Tensilon test,
      acetylcholine receptor antibodies, repetitive nerve stimulation and single fiber
      electromyography for the diagnosis of myasthenia gravis. After examining inter
      study heterogeneity for each diagnostic modality, we calculated pooled estimates
      of sensitivity and specificity as well as positive and negative likelihood
      ratios. Results are reported separately for ocular and generalized myasthenia.
      Studies that have examined the performance of anti-acetylcholine receptor
      antibody testing and single fiber electromyography were generally of better
      quality than those that examined other diagnostic modalities. We suggest that
      caution should be exercised in the interpretation of the diagnostic performance
      of these tests given the methodological limitations of the studies upon which
      test performance is based.

PMID- 16793270
TI  - Myotilinopathy in a family with late onset myopathy.
AB  - Mutations in titin are well known cause of late onset autosomal dominant distal
      myopathy. Mutations in another sarcomeric protein, myotilin, were first
      identified in two families with dominant limb girdle muscular phenotype.
      Recently, however, myotilin mutations have been associated with more distal
      phenotypes in patients with late onset myofibrillar myopathy. We report here a
      multigenerational French family in which gene sequencing identified a S60F
      myotilin mutation in all patients with full penetrance despite very late onset.
      The family was originally reported as a distal myopathy but intrafamilial
      variability was remarkable with proximal or distal muscle weakness or both.
      Extended morphological characteristics of muscle biopsy findings in
      myotilinopathy indicate that immunohistochemistry may be important for selection
      of molecular genetic approach in myofibrillar myopathy.

PMID- 16793271
TI  - Phosphatidylinositol 4-kinases: old enzymes with emerging functions.
AB  - Phosphoinositides account for only a tiny fraction of cellular phospholipids but
      are extremely important in the regulation of the recruitment and activity of many
      signaling proteins in cellular membranes. Phosphatidylinositol (PtdIns) 4-kinases
      generate PtdIns 4-phosphate, the precursor of important regulatory
      phosphoinositides but also an emerging regulatory molecule in its own right. The
      four mammalian PtdIns 4-kinases regulate a diverse array of signaling events, as
      well as vesicular trafficking and lipid transport, but the mechanisms by which
      their lipid product PtdIns 4-phosphate controls these processes is only beginning
      to unfold.

PMID- 16793272
TI  - Effects of changing protocol, grade, and direction on the preferred gait
      transition speed during human locomotion.
AB  - Although the preferred transition speed (PTS) reported by various researchers is
      relatively consistent, the amount of observed hysteresis (difference between the
      walk-run and the run-walk transition speed) varies considerably. Variations in
      reported hysteresis appear to be related to the protocol used to determine the
      transition speeds. This investigation compared the PTS, and the amount of
      hysteresis observed between the incremental and continuous protocols at various
      inclination conditions. The PTS was significantly greater in the continuous than
      the incremental protocol within both the 10% and 15% inclination conditions. The
      amount of hysteresis, however, did not vary significantly between protocols nor
      between inclination conditions. In the incremental protocol, the amount of
      hysteresis appears to be related to the size of the speed increment used. In the
      continuous protocol, the amount of hysteresis could be related to the rate of
      treadmill acceleration.

PMID- 16793273
TI  - A role for zinc in postsynaptic density asSAMbly and plasticity?
AB  - Chemical synapses are asymmetric cell junctions that mediate communication
      between neurons. Multidomain scaffolding proteins of the Shank family act as
      major organizing elements of the "postsynaptic density"--that is, the
      cytoskeletal protein matrix associated with the postsynaptic membrane. A recent
      study has shown that the C-terminal sterile alpha-motif or "SAM domain" of Shank3
      (also known as ProSAP2) can form two-dimensional sheets of helical fibers.
      Assembly and packaging of these fibers are markedly enhanced by the presence of
      Zn2+ ions. Zn2+ can be released together with glutamate from synaptic vesicles
      and can enter the postsynaptic cell through specific ionotropic receptors. Based
      on these observations, we propose a new model of synaptic plasticity in which
      Zn2+ influx directly and instantly modulates the structure and function of the
      postsynaptic density.

PMID- 16793275
TI  - Synthesis of benzenepropanamine analogues as non-detergent spermicides with
      antitrichomonas and anticandida activities.
AB  - Fifteen analogues of benzenepropanamine were synthesized and evaluated for their
      spermicidal as well as microbicidal activities against Trichomonas vaginalis and
      Candida spp. Several compounds showed appreciable dual activities. Compound 12
      exhibited good spermicidal (MEC=0.1%) along with substantial anticandidal
      (MIC=0.05%) activities, while compounds 3 and 6 showed significant microbicidal
      activities with moderate spermicidal effect. The SAR of these structures is being
      discussed here in this communication. It is concluded that suitable structural
      modifications in this class of compounds at 3-amino position may lead to a potent
      spermicide with associated microbicidal activity.

PMID- 16793274
TI  - Synthesis and biological assays of E-ring analogs of camptothecin and
      homocamptothecin.
AB  - Analogs of the anti-tumor agent camptothecin with both closed E-rings (lactone
      and ether) and open E-rings (reduced acid, hydrazide, and protected Weinreb
      amide) have been prepared and tested in topoisomerase and cellular assays. The
      results provide insights into the structural features of the camptothecin E-ring
      that affect biological activity.

PMID- 16793276
TI  - Inhibition of type 2 isopentenyl diphosphate isomerase from Methanocaldococcus
      jannaschii by a mechanism-based inhibitor of type 1 isopentenyl diphosphate
      isomerase.
AB  - Type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2, EC
      5.3.3.2) is a flavoprotein, which requires FMN, NADPH, and Mg2+ for the activity
      to convert isopentenyl diphosphate to dimethylallyl diphosphate. For
      investigation of the reaction mechanism of IDI-2, 3,4-epoxy-3-methylbutyl
      diphosphate (EIPP), a mechanism-based inhibitor of type 1 IDI (IDI-1), was
      treated with the overexpressed IDI-2 (MjIDI) from methanogenic archaeon
      Methanocaldococcus jannaschii. EIPP showed the time- and concentration-dependent
      inhibition (KI; 56.5 mM, k(inact); 0.10 s(-1), k(inact)/KI; 1.76 s(-1)M(-1)) and
      the UV-vis spectrum of MjIDI after treatment with EIPP was apparently different
      from that of the untreated MjIDI. These results indicated that EIPP modified FMN
      through a covalent bond in the active site of MjIDI. The formed EIPP-FMN complex
      was separated from the reaction mixture and the spectrometric analysis of the
      complex suggested that the reduced form of FMN bound to EIPP at the N5 position.
      These results may suggest that the IDI-2 reaction is similar to IDI-1, which
      proceeds via carbocation-type intermediate.

PMID- 16793277
TI  - Stereoselective allyl transfer to chiral alpha-methoxycarbaldehydes: a model
      study related to the C-9/C-15 fragment of geldanamycin.
AB  - The enantiomerically pure alpha-methoxycarbaldehyde 3 was prepared from l-leucine
      in five steps and 31% overall yield. The aldehyde was subjected to a
      diastereoselective BF3-mediated crotylation with silane 4 and to various reagent
      controlled addition reactions. The configuration of aldol addition products 19
      and 20 was proven by single crystal X-ray crystallography. Based on these data
      spectral comparison allowed an unambiguous assignment of the desired anti,syn
      crotylation product 2b and of the syn,syn-crotylation product 2a. Unexpectedly,
      product 2a of the BF3-mediated crotylation is formally the product of chelation
      control. The anti,syn-crotylation product 2b, which is a model for the C-9/C-15
      fragment of geldanamycin, was obtained by a reagent-controlled crotylation with
      the chiral (Z)-crotylborane 23.

PMID- 16793278
TI  - A deconvolution method for the separation of specific versus nonspecific
      interactions in noncovalent protein-ligand complexes analyzed by ESI-FT-ICR mass
      spectrometry.
AB  - A method to separate specific and nonspecific noncovalent interactions observed
      in ESI mass spectra between a protein and its ligands is presented. Assuming
      noncooperative binding, the specific ligand binding is modeled as a statistical
      distribution on identical binding sites. For the nonspecific fraction we assume a
      statistical distribution on a large number of "nonspecific" interacting sites.
      The model was successfully applied to the noncovalent interaction between the
      protein creatine kinase (CK) and its ligands adenosine diphosphate (ADP) and
      adenosine triphosphate (ATP) that both exhibit nonspecific binding in the mass
      spectrum. The two sequential dissociation constants obtained by applying our
      method are K(1,diss) = 11.8 +/- 1.5 microM and K(2,diss) = 48 +/- 6 microM for
      ADP. For ATP, the constants are K(1,diss) = 27 +/- 7 microM and K(2,diss) = 114
      +/- 27 microM. All constants are in good correlation with reported literature
      values. The model should be valuable for systems with a large dissociation
      constant that require high ligand concentrations and thus have increased
      potential of forming nonspecific adducts.

PMID- 16793279
TI  - Ion trajectory simulation for electrode configurations with arbitrary geometries.
AB  - A multi-particle ion trajectory simulation program ITSIM 6.0 is described, which
      is capable of ion trajectory simulations for electrode configurations with
      arbitrary geometries. The electrode structures are input from a 3D drawing
      program AutoCAD and the electric field is calculated using a 3D field solver
      COMSOL. The program CreatePot acts as interface between the field solver and
      ITSIM 6.0. It converts the calculated electric field into a field array file
      readable by ITSIM 6.0 and ion trajectories are calculated by solving Newton's
      equation using Runge-Kutta integration methods. The accuracy of the field
      calculation is discussed for the ideal quadrupole ion trap in terms of applied
      mesh density. Electric fields of several different types of devices with 3D
      geometry are simulated, including ion transport through an ion optical system as
      a function of pressure. Ion spatial distributions, including the storage of
      positively charged ions only and simultaneous storage of positively/negatively
      charged ions in commercial linear ion traps with various geometries, are
      investigated using different trapping modes. Inelastic collisions and collision
      induced dissociation modeled using RRKM theory are studied, with emphasis on the
      fragmentation of n-butylbenzene inside an ideal quadrupole ion trap. The mass
      spectrum of 1,3-dichlorobenzene is simulated for the rectilinear ion trap device
      and good agreement is observed between the simulated and the experimental mass
      spectra. Collisional cooling using helium at different pressures is found to
      affect mass resolution in the rectilinear ion trap.

PMID- 16793280
TI  - How to find a prion: [URE3], [PSI+] and [beta].
AB  - Infectious proteins (prions) in yeast or other microorganisms can be identified
      by genetic methods of rather general applicability. Infection in yeast means
      transfer by cytoplasmic mixing (cytoduction), a property of all non-chromosomal
      genetic elements whether plasmids, viruses, or prions. Prions can be diagnosed by
      reversible curability, increased occurrence when the corresponding protein is
      overproduced, a requirement for the gene for the corresponding protein for
      propagation, and, in some cases, similarity of phenotype of: (a) mutations in the
      gene for the protein and (b) the presence of the prion. This approach is
      illustrated with [URE3], an amyloid-based prion of the regulator of nitrogen
      catabolism, Ure2p and [PSI(+)] as a prion of the translation termination factor
      Sup35p. The prion concept is not limited to infectious amyloids, but includes
      proteins whose active form is necessary for the activation of the inactive
      precursor. We detail methods used in studies of [URE3] and [beta], a self
      activating protease, some of which are of broad application.

PMID- 16793281
TI  - Biochemical and genetic methods for characterization of [PIN+] prions in yeast.
AB  - The glutamine- and asparagine-rich Rnq1p protein in Saccharomyces cerevisiae can
      exist in the cell as a soluble monomer or in one of several aggregated,
      infectious, prion forms called [PIN(+)]. Interest in [PIN(+)] is heightened by
      its ability to promote the conversion of other proteins into a prion or an
      aggregated amyloid state. However, little is known about the function of Rnq1p,
      which makes it difficult to assay the phenotypes associated with its normal vs.
      prion forms. In this chapter, we describe methods used to detect [PIN(+)] and
      distinguish between different variations of the prion. Genetic methods are based
      on the ability of the [PIN(+)] prion to facilitate the appearance of another
      yeast prion, [PSI(+)], which has an easily detectable phenotype. Biochemical
      methods exploit the fact that the [PIN(+)] prion exists in the yeast cytosol in
      the form of large aggregates, composed of SDS-stable subparticles. Sucrose
      gradient centrifugation, agarose SDS electrophoresis and GFP fusions are used to
      distinguish between aggregates and subparticles from different [PIN(+)] variants.

PMID- 16793282
TI  - Application of photobleaching for measuring diffusion of prion proteins in
      cytosol of yeast cells.
AB  - Measurement of fluorescence recovery after photobleaching (FRAP) is a non
      invasive technique for studying protein dynamics in real time in living cells.
      FRAP studies are carried out on proteins tagged with green fluorescent protein
      (GFP) or one of its spectral variants. Illumination with high intensity laser
      light irreversibly bleaches the GFP fluorescence but has no effect on protein
      function. By photobleaching a limited region of the cytoplasm, the rate of
      fluorescence recovery provides a measure of the rate of protein diffusion. A
      detailed description of the FRAP technique is given, including its application to
      measuring the mobility of GFP-tagged Sup35p in [psi(-)] and [PSI(+)] cells.

PMID- 16793283
TI  - Purification of recombinant annexins without the use of phospholipids.
AB  - Due to their involvement in a variety of physiological and pathological
      processes, different isoforms of annexins are being utilized as markers of some
      human diseases and bio-imaging of tissue injury (due to apoptosis), and have been
      proposed as drug delivery vehicles. These, in addition to extensive biophysical
      studies on the role of annexins in organizing lipid domains in biological
      membranes, have necessitated development of an efficient protocol for producing
      annexins in bulk quantities. In this paper, we report a one-step purification
      protocol for annexin a5 without using lipid vesicles or involving any column
      chromatographic step. Depending on the growth and expression condition, a
      fraction of recombinant annexin a5 (cloned in pET3d vector) was sequestered into
      inclusion bodies. When these inclusion bodies were dissolved in 6 M urea,
      subjected to a 10-fold snap dilution in the presence of 5 mM Ca(2+) and stored
      overnight at 4 degrees C, annexin a5 was precipitated as a homogenous protein as
      judged by SDS-PAGE. This one-step purification protocol produced about 35 mg of
      highly purified annexin a5 per liter of bacterial culture. The annexin a5
      purified from inclusion bodies exhibited similar properties to that obtained from
      the soluble fraction using the conventional lipid-partitioning approach. Our
      purification protocol for annexin a5 elaborated herein is equally effective for
      purification of annexin A2, and we believe, will serve as general protocol for
      purifying other annexins in bulk quantities for diagnostic as well as detailed
      biophysical studies.

PMID- 16793284
TI  - Overproduction, purification, and biochemical characterization of the dual
      specificity H1 protein phosphatase encoded by variola major virus.
AB  - Smallpox, a highly contagious infectious disease caused by the variola major
      virus, has an overall mortality rate of about 30%. Because there currently is no
      specific treatment for smallpox, and the only prevention is vaccination, there is
      an urgent need for the development of effective antiviral drugs. The dual
      specificity protein phosphatase encoded by the smallpox virus (H1) is essential
      for the production of infectious viral particles, making it a promising molecular
      target for antiviral therapeutics. Here, we report the molecular cloning,
      overproduction, purification, and initial biochemical characterization of H1
      phosphatase, thereby paving the way for the discovery of small molecule
      inhibitors.

PMID- 16793285
TI  - A comparison of muscle thin filament models obtained from electron microscopy
      reconstructions and low-angle X-ray fibre diagrams from non-overlap muscle.
AB  - The regulation of striated muscle contraction involves changes in the
      interactions of troponin and tropomyosin with actin thin filaments. In resting
      muscle, myosin-binding sites on actin are thought to be blocked by the coiled
      coil protein tropomyosin. During muscle activation, Ca2+ binding to troponin
      alters the tropomyosin position on actin, resulting in cyclic actin-myosin
      interactions that accompany muscle contraction. Evidence for this steric
      regulation by troponin-tropomyosin comes from X-ray data [Haselgrove, J.C., 1972.
      X-ray evidence for a conformational change in the actin-containing filaments of
      verterbrate striated muscle. Cold Spring Habor Symp. Quant. Biol. 37, 341-352;
      Huxley, H.E., 1972. Structural changes in actin and myosin-containing filaments
      during contraction. Cold Spring Habor Symp. Quant. Biol. 37, 361-376; Parry,
      D.A., Squire, J.M., 1973. Structural role of tropomyosin in muscle regulation:
      analysis of the X-ray diffraction patterns from relaxed and contracting muscles.
      J. Mol. Biol. 75, 33-55] and electron microscope (EM) data [Spudich, J.A.,
      Huxley, H.E., Finch, J., 1972. Regulation of skeletal muscle contraction. II.
      Structural studies of the interaction of the tropomyosin-troponin complex with
      actin. J. Mol. Biol. 72, 619-632; O'Brien, E.J., Gillis, J.M., Couch, J., 1975.
      Symmetry and molecular arrangement in paracrystals of reconstituted muscle thin
      filaments. J. Mol. Biol. 99, 461-475; Lehman, W., Craig, R., Vibert, P., 1994.
      Ca2+-induced tropomyosin movement in Limulus thin filaments revealed by three
      dimensional reconstruction. Nature 368, 65-67] each with its own particular
      strengths and limitations. Here we bring together some of the latest information
      from EM analysis of single thin filaments from Pirani et al. [Pirani, A., Xu, C.,
      Hatch, V., Craig, R., Tobacman, L.S., Lehman, W. (2005). Single particle analysis
      of relaxed and activated muscle thin filaments. J. Mol. Biol. 346, 761-772], with
      synchrotron X-ray data from non-overlapped muscle fibres to refine the models of
      the striated muscle thin filament. This was done by incorporating current atomic
      resolution structures of actin, tropomyosin, troponin and myosin subfragment-1.
      Fitting these atomic coordinates to EM reconstructions, we present atomic models
      of the thin filament that are entirely consistent with a steric regulatory
      mechanism. Furthermore, fitting the atomic models against diffraction data from
      skinned muscle fibres, stretched to non-overlap to preclude crossbridge binding,
      produced very similar results, including a large Ca2+-induced shift in
      tropomyosin azimuthal location but little change in the actin structure or
      apparent alteration in troponin position.

PMID- 16793286
TI  - Effects of joint angle and age on ankle dorsi- and plantar-flexor strength.
AB  - This study aimed at examining the effects of joint angle and age on the maximal
      voluntary contraction (MVC) torque, for the agonist and antagonist muscle groups
      around the ankle, i.e., the dorsi- and plantar-flexors. To this aim, neural and
      muscular factors were investigated in two groups of healthy men: 11 young (mean
      age, 24 years) and 18 older (mean age, 78 years). Plantar-flexion (PF) and
      dorsiflexion (DF) isometric MVC torques were measured in three different ankle
      joint angles and surface electromyographic activities of the triceps surae and of
      the tibialis anterior muscles were recorded. The main findings were that the DF
      to-PF MVC torque ratio varied with joint angle and age, indicating that aging
      affected at different rates the two muscle groups: this ratio was always higher
      in older adults because of the PF strength decline with aging. Furthermore, the
      DF MVC torque-angle relationship appeared to be especially explained by neural
      factors, whereas the relationship in PF seemed to be mainly due to muscular
      parameters. These relationships would not be a discriminating factor between the
      two age groups. As a consequence, measurements at one ankle joint angle, whatever
      the angle, are thus enough to examine the differences within age groups and to
      perform a rapid assessment of the imbalance at the ankle joint.

PMID- 16793287
TI  - Cortical responses to contextual influences in amodal completion.
AB  - Amodal completion refers to the process in the visual system that enables us to
      perceive partly occluded objects as whole objects. Both the overall shape of a
      visual object (global aspect) and the region immediately surrounding the occluder
      (local aspect) are known to determine the process of completion. We investigated
      the influence of overall shape context in completion on human brain activity
      using MEG recordings. Subjects were presented with two different types of shapes
      that were partly occluded by a rectangle. In the so-called convergent shapes, the
      local and global contexts trigger the same completion, and in the so-called
      divergent shapes, local and global contexts trigger different completions. The
      occluder was removed after 1 s, revealing the whole (completed) shape where
      expectancies based on the local and global context could either be fulfilled or
      violated. We found an early (from 200 ms on) left occipital component, which was
      predominantly sensitive to the figural aspects of the uncovered continuation, but
      was also modulated by the congruency between the physical shape and the perceived
      shape (based on the contextual cues). In contrast, an early right occipital
      component and a later (400 ms) anterior temporal component were sensitive only to
      the congruency between the physical and the perceived shape, showing the
      relevance of the global context in amodal completion.

PMID- 16793288
TI  - The predictive value of white matter organization in posterior parietal cortex
      for spatial visualization ability.
AB  - Humans differ substantially in their ability to imagine spatial transformations
      of novel stimuli (i.e., mental rotation). Whereas "high-spatial" individuals are
      able to maintain high-quality representations even after complex mental
      transformations, "low-spatial" individuals often experience substantial
      degradation of the initial representation. Even though subdivisions of the
      posterior parietal cortex are known to instantiate the necessary spatial
      transformations, a direct demonstration of neuroanatomical differences predicting
      this behavioral variability is currently missing. Because recent evidence
      suggests that interindividual differences on the behavioral level might be
      related to regionally specific white matter organization, we addressed this
      question using diffusion tensor imaging in combination with well-established
      psychometric tests. As expected, behavioral results revealed a substantial
      disparity in mental rotation performance. Most importantly, despite controlling
      for differences in spatial short-term memory capacity, we observed a tight
      relationship between mental rotation proficiency and white matter organization
      near the anterior part of the intraparietal sulcus. Whereas high-level
      proficiency was paralleled by high fractional anisotropy (FA) values, the
      opposite pattern was observed in "low spatials". The present results strongly
      indicate that the efficiency of information transfer between posterior parietal
      regions involved in the mental transformation process could be one decisive
      factor in individual spatial visualization proficiency.

PMID- 16793289
TI  - Invasive and noninvasive lung function measurements in rodents.
AB  - Precise and repeatable measurements of pulmonary function in intact mice or rats
      are becoming increasingly important for experimental investigations on various
      respiratory disorders like asthma and for pharmacological, safety-pharmacological
      or toxicological testing of drugs or chemicals. This review provides a short
      overview of typical in-vivo measurement techniques, discusses their advantages
      and disadvantages and presents two of these methods in detail: the noninvasive
      head-out body plethysmography and an invasive but repeatable body-plethysmography
      in orotracheally intubated rodents. It will be demonstrated that these methods
      are able to monitor bronchoconstriction in safety-pharmacological tests or in
      asthma models showing early allergic response or late airway hyperresponsiveness
      in response to inhaled allergens and demonstrate drug effects on pulmonary
      endpoints. The changes in the respective parameters such as tidal midexpiratory
      flow (EF(50)) or lung resistance in typical bronchoconstriction models have been
      measured in the same animals and compared for validation purposes. It is
      concluded that both invasive and noninvasive pulmonary function tests are capable
      of detecting allergen-specific as well as non-allergic bronchoconstriction in
      intact mice or rats. The invasive determination of resistance is superior in
      sensitivity, whereas the noninvasive EF(50) method is particularly appropriate
      for quick and repeatable screening of respiratory function in large numbers of
      mice and rats or if the conscious animal has to be tested (e.g. safety
      pharmacology). The use of both techniques in a large number of studies in the
      last years have demonstrated that they provide useful and necessary information
      on pulmonary mechanics in studies of respiratory disorders including experimental
      models of asthma, in investigations of pulmonary pharmacology, safety
      pharmacology and toxicology in mice and rats.

PMID- 16793290
TI  - Altered ion transport and responsiveness to methacholine and hyperosmolarity in
      air interface-cultured guinea-pig tracheal epithelium.
AB  - INTRODUCTION: Challenge of guinea-pig tracheal epithelium with hyperosmolar
      solution alters ion transport and evokes the release of epithelium-derived
      relaxing factor (EpDRF). Cultured tracheal epithelial cells (CE) offer the
      potential to examine biochemical pathways related to EpDRF release, but whether
      the bioelectric properties and responses of fresh, adherent epithelial cells (FE)
      are modeled by CE has not been established. METHODS: Tracheal epithelial cells
      grown in air-interface culture and fresh tracheal segments were mounted in Ussing
      chambers to determine short circuit current (I(sc)) and transepithelial
      resistance (R(t)) and to compare responses to transport inhibitors, methacholine
      and hyperosmolarity. RESULTS: Significant differences in basal I(sc) and R(t)
      between FE and CE were observed (I(sc), 41.3+/-3.5 and 8.5+/-0.8 microA/cm(2),
      P<0.05; R(t), 106+/-7 and 422+/-4 Omega cm(2), P<0.05; respectively); basal
      spontaneous potential difference values were not different (4.2+/-0.3 and 3.4+/
      0.3 mV, respectively). Amiloride (mucosal, 3 x 10(-5) M), bumetanide
      (basolateral, 10(-5) M) and ouabain (basolateral, 10(-5) M) reduced I(sc) equally
      in FE and CE. In contrast, NPPB (10(-5) M) in the presence of amiloride had a
      differential effect, decreasing I(sc) by 11% in FE and 71% in CE (P<0.05).
      Iberiotoxin (basolateral, 10(-7) M) was without effect in either preparation. In
      FE, serosal methacholine (3x10(-5) M) elicited an NPPB-insensitive monotonic
      increase in I(sc), but in CE caused a large, transient, NPPB-inhibitable increase
      which was followed by an NPPB-resistant plateau. Addition of apical D-mannitol
      (0.3-267 mosM) to increase osmolarity decreased I(sc) in FE, whereas in CE d
      mannitol initially increased (0.3-84.3 mosM) and then decreased (84.3-267 mosM)
      I(sc). DISCUSSION: Cell culture causes substantial changes in the bioelectric and
      pharmacological properties of respiratory epithelium. Caution should be exercised
      when using CE as a substitute for FE in studies of ion transport- and cell volume
      dependent processes.

PMID- 16793291
TI  - Overlap cases of eyelid myoclonia with absences and juvenile myoclonic epilepsy.
AB  - Eyelid myoclonia with absences (EMA) and juvenile myoclonic epilepsy (JME) are
      two separate epileptic syndromes included in the new classification of epilepsies
      and epileptic syndromes by ILAE in 2001. Both are idiopathic generalized
      epilepsies with their clinical onset in the first two decades. EMA is
      characterized by eyelid myoclonia associated with absences and photosensitivity.
      Self-induced seizures are frequently seen in EMA. It can be associated with
      mildly mental retardation and resistance to treatment. JME includes three types
      of generalized seizures: typical absences, myoclonic jerks and generalized tonic
      clonic seizures. The myoclonic jerks occur almost exclusively on awakening,
      involve preferently the upper extremities, may rarely affect the lower
      extremities or the entire body. More severe attacks may be accompanied by a fall.
      The myoclonic jerks occur rarely in EMA. They are usually mild and are freqently
      restricted to the upper extremities. Generalized tonic-clonic seizures,
      photosensitivity and generalized polyspike-wave discharges provoked by eye
      closure are features of both epileptic syndromes. In this study, we describe four
      female patients with eyelid myoclonia associated with absences, myoclonic jerks
      causing falling down and rare generalized tonic-clonic seizures. All patients had
      good school performance and total seizure control under sodium valproate
      treatment. Their EEGs show generalized polyspike-wave discharges with a frequency
      of 3.5-6Hz always appearing a few seconds after eye closure and photoparoxysmal
      response. These patients show the characterictics of both epileptic syndromes. It
      is clinically important to make a syndromic diagnosis for an optimum advise on
      treatment, lifestyle restrictions and prognosis. In this study, we have gathered
      evidence that EMA and JME are dynamic syndromes that tend to evolve into one
      another.

PMID- 16793292
TI  - Cell cycle analysis of in vitro cultured goral (Naemorhedus caudatus) adult skin
      fibroblasts.
AB  - The present study was undertaken to examine cell cycle characteristics of
      endangered Goral (CITES Appendix I) adult skin fibroblasts. Seven experiments
      were performed, each with a one-way completely randomized design involving three
      replicates. Least significant difference (LSD) was used to determine variation
      among treatment groups. Experiment I focused on the effects of cycling, serum
      starved, and fully confluent stages of Goral cells. In Experiments II and III,
      the effects of different antioxidants like beta-mercaptoethanol (beta-ME, 10
      microM), cysteine (2 mM), and glutathione (2 mM) were examined after cells were
      fully confluent without serum starvation for 24 h and 4 h, respectively. In
      Experiments IV and V, three protease inhibitors, namely 6-dimethylaminopurine (6
      DMAP, 2 mM), cycloheximide (7.5 microg/ml) and cytochalasin B (7.5 microg/ml),
      were used as in Experiment II. In Experiments VI and VII, the effect of different
      levels of dimethylsulphoxide (DMSO) at 0%, 0.5%, 1.0% and 2.5% were tested by
      flow cytometry (FACS). In Experiment I, 68.7% of Goral skin fibroblasts reached
      the G(0)/G(1) stage (2C DNA content) when subjected to the serum-starved medium,
      which was more than the cycling (64.9%) and fully confluent groups (61.0%) (P >
      0.05). Among the chemically treated group, beta-ME, cysteine and DMSO showed
      better results for synchronization of G(0) + G(1) phases than cycling, serum
      starved and fully confluent groups. It can thus be concluded that beta-ME,
      cysteine and DMSO at certain concentrations can synchronize the cell cycle
      effectively, which could have a positive impact on somatic cell nuclear transfer
      in the goral.

PMID- 16793294
TI  - Membrane conductance in trained and untrained subjects using either steady state
      or single breath measurements of NO transfer.
AB  - The aim of this work was to define the relationship between membrane conductance
      for NO (Dm) and physical activity by using either the steady state NO transfer
      (T(LNO)SS) or the single breath method (T(LNO)SB), making the hypothesis that NO
      transfer is only limited by the membrane. Alterations in T(LNO)SS with lung
      volume during tidal ventilation were measured in six subjects at rest and during
      steady exercise at 30, 60, and 80% of maximal aerobic power (MAP). A fast
      responding chemoluminescent NO analyser was used. Two calculation methods were
      used by sampling NO: (1) at mid-tidal volume, (2) in the middle of the alveolar
      plateau. T(LNO)SB at rest and maximal oxygen consumption (V(.-)O(2)max) were also
      measured in 18 other subjects. At rest T(LNO)SS with method 2 was 192% of the
      value given by method 1. T(LNO)SS with method 1 increased by 50% with 80% MAP as
      it did not change with method 2. Method 2 seemed inaccurate. T(LNO)SB at rest,
      which is closely related to Dm, was correlated to age and V(.-)O(2)max,
      T(LNO)SB=182-1.2 age+24.3 V(.-)O(2) max(l min(-1)) (p<0.01, r(2)=0.72). The
      T(LNO)SS and T(LNO)SB versus lung volume relationships suggest an influence of
      the breathing pattern on Dm. Dm can be estimated either by these two NO transfer
      methods, however the use of the T(LNO)SS method is highly sensitive to the
      alveolar sampling level. Dm increase during exercise is a function of MAP. Dm at
      rest decreases with age as it increases with MAP.

PMID- 16793293
TI  - Mating factor linkage and genome evolution in basidiomycetous pathogens of
      cereals.
AB  - Sex in basidiomycete fungi is controlled by tetrapolar mating systems in which
      two unlinked gene complexes determine up to thousands of mating specificities, or
      by bipolar systems in which a single locus (MAT) specifies different sexes. The
      genus Ustilago contains bipolar (Ustilago hordei) and tetrapolar (Ustilago
      maydis) species and sexual development is associated with infection of cereal
      hosts. The U. hordei MAT-1 locus is unusually large (approximately 500 kb) and
      recombination is suppressed in this region. We mapped the genome of U. hordei and
      sequenced the MAT-1 region to allow a comparison with mating-type regions in U.
      maydis. Additionally the rDNA cluster in the U. hordei genome was identified and
      characterized. At MAT-1, we found 47 genes along with a striking accumulation of
      retrotransposons and repetitive DNA; the latter features were notably absent from
      the corresponding U. maydis regions. The tetrapolar mating system may be
      ancestral and differences in pathogenic life style and potential for inbreeding
      may have contributed to genome evolution.

PMID- 16793295
TI  - Bovine tuberculosis--another view from down under.

PMID- 16793296
TI  - Comorbidity of low back pain: representative outcomes of a national health study
      in the Federal Republic of Germany.
AB  - BACKGROUND: Unlike other biopsychosocial risk factors, the role of comorbidity in
      low back pain is largely unknown. AIMS: The purpose is (1) to generate prevalence
      data on back pain in the total adult population and (2) to identify the most
      common physical comorbidities in subjects with back pain. This paper also (3)
      analyses the gender-specific and age-specific comorbidity structure. METHODS: The
      National German Health Survey is the first study to provide the basis for a
      representative nationwide analysis of back pain prevalence and the associated
      comorbidities. The net sample comprises a total of 7124 Germans aged 18-79.
      RESULTS: One in three Germans (34%) experienced back pain during the seven days
      prior to being interviewed. The one-year prevalence rate is 59%. All the
      morbidities investigated by us are more common in subjects with back pain than in
      individuals without back pain. The most common comorbidities associated with back
      pain are musculoskeletal disorders like rheumatoid arthritis, osteoarthritis and
      osteoporosis, followed by cardiovascular and cerebrovascular disease.
      CONCLUSIONS: The present study investigating 31 physical diseases is the most
      extensive analysis to date on the topic of back pain and comorbidity. This is an
      attempt to cast light on the tangled relationships involved in developing and
      coping with back pain. In view of the large percentage of unspecific back pain,
      we believe it is important for physicians treating back pain to extend their
      history and diagnostic analysis skills to embrace comorbidities related to the
      back pain.

PMID- 16793297
TI  - Determination of association constants at moderately fast chemical exchange:
      complexation of camphor enantiomers by alpha-cyclodextrin.
AB  - Association constants in weak molecular complexes can be determined by analysis
      of chemical shifts variations resulting from changes of guest to host
      concentration ratio. In the regime of very fast exchange, i.e., when exchange
      rate is several orders of magnitude larger than the Larmor angular frequency
      difference of the observed resonance in free and complexed molecule, the apparent
      position of averaged resonance is a population-weighted mean of resonances of
      particular forms involved in the equilibrium. The assumption of very fast
      exchange is often, however, tacitly admitted in literature even in cases where
      the process of interest is much slower than required. We show that such an
      unjustified simplification may, under certain circumstances, lead to significant
      underestimation of association constant and, in consequence, to non-negligible
      errors in Gibbs free energy under determination. We present a general method,
      based on iterative numerical NMR line shape analysis, which allows one for the
      compensation of chemical exchange effects, and delivers both the correct
      association constants and the exchange rates. The latter are not delivered by the
      other mentioned method. Practical application of our algorithm is illustrated by
      the case of camphor-alpha-cyclodextrin complexes.

PMID- 16793298
TI  - Wave function analysis of MHC-peptide interactions.
AB  - We have carried out an analysis of the wave function data for three MHC-peptide
      complexes: HLA-DRbeta1*0101-HA, HLA-DRbeta1*0401-HA and HLA-DRbeta1*0401-Col. We
      used quantum chemistry computer programs to generate wave function coefficients
      for these complexes, from which we obtained both molecular and atomic orbital
      data for both pocket and peptide amino acids within each pocket region. From
      these discriminated data, interaction molecular orbitals (IMOs) were identified
      as those with large and similar atomic orbital coefficient contributions from
      both pocket and peptide amino acids. The present results correlate well with our
      previous research where only electrostatic moments were used to explore molecular
      component interactions. Furthermore, we show a quantum chemical methodology to
      produce more fine-grained results concerning amino acid behavior in the MHC
      peptide interaction.

PMID- 16793300
TI  - Seasonal changes in body composition of Ctenomys talarum (Rodentia:
      Octodontidae): an herbivore subterranean rodent.
AB  - Ctenomys talarum is a subterranean herbivorous rodent whose burrow systems
      exhibit particular characteristics, distinct from other subterranean
      environments. We studied seasonal variation in body composition of C. talarum in
      relation to energetic requirements. Body lipid content seasonally changed in C.
      talarum, related to reproductive cycle and thermorregulatory mechanisms. A
      decrease in protein body content was found only in spring. Ash content of females
      was lowest when most of them are in post partum estro. Observed variations in
      water body content could be associated with plant water content and/or metabolic
      regulation. Our results show the occurrence of seasonal variations in body
      composition in C. talarum, which could be related to the high cost of
      reproduction and the subterranean life style of this species.

PMID- 16793301
TI  - Exploiting the bootstrap method for quantifying parameter confidence intervals in
      dynamical systems.
AB  - A quantitative description of dynamical systems requires the estimation of
      uncertain kinetic parameters and an analysis of their precision. A method
      frequently used to describe the confidence intervals of estimated parameters is
      based on the Fisher-Information-Matrix. The application of this traditional
      method has two important shortcomings: (i) it gives only lower bounds for the
      variance of a parameter if the solution of the underlying model equations is non
      linear in parameters. (ii) The resulting confidence interval is symmetric with
      respect to the estimated parameter. Here, we show that by applying the bootstrap
      method a better approximation of (possibly) asymmetric confidence intervals for
      parameters could be obtained. In contrast to previous applications devoted to non
      parametric problems, a dynamical model describing a bio-chemical network is used
      to evaluate the method.

PMID- 16793299
TI  - Docking studies of agonists and antagonists suggest an activation pathway of the
      A3 adenosine receptor.
AB  - Structural determinants of ligand efficacy in the human A(3) adenosine receptor
      (AR) were studied using pharmacophore and docking analyses of various categories
      of A(3) selective ligands: inverse agonist, neutral antagonist (nonnucleoside and
      nucleoside), and agonist (partial and full). The homology modeling of GPCRs was
      adapted to provide two templates: the rhodopsin-based resting state for
      antagonist binding and a putative Meta I state, conformationally altered at a key
      residue (W6.48), for agonist binding. The preferential binding domains and/or
      local conformational changes associated with docking of three high affinity
      A(3)AR ligands were compared: inverse agonist PSB-11 1 ((R)-8-ethyl-4-methyl-2
      phenyl-imidazo[2,1-i]purin-5-one); neutral antagonist MRE-3008F20 7 (5-[[(4
      methoxyphenyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)pyra-zolo[4,3-e]1,2,4
      triazolo[1,5-c]pyrimidine), and full agonist Cl-IB-MECA 21 (2-chloro-N(6)-(3
      iodobenzyl)-5'-N-methylcarboxamidoadenosine) to define a distinct recognition
      mode for each. Ribose-containing agonists were more hydrophilic than
      nonnucleoside antagonists, and H-bonding ability at the ribose 3'- and 5'
      positions was required for agonism. From the receptor perspective, common
      requirements for activation included the destabilization of H-bond networks at
      W6.48 and H7.43, the specific interactions of the ribose moiety in its putative
      hydrophilic pocket at T3.36, S7.42, and H7.43, the stabilization of the complex
      by inward movement of F5.43, and the characteristic rotation of W6.48. By
      analogy, outward rotation of the W6.48 side-chain upon activation of an
      internally-crosslinking mutant M(3) muscarinic receptor was indicated by
      constrained molecular dynamics (MD). Our results are consistent with an anti
      clockwise rotation (from the extracellular view) of transmembrane domains 3, 5,
      6, and 7, as proposed for other Family A GPCRs. Thus, the putative conformational
      changes associated with A(3)AR activation indicate a shared mechanism of GPCR
      activation similar to rhodopsin.

PMID- 16793302
TI  - Expression profiling of genes involved in paclitaxel biosynthesis for targeted
      metabolic engineering.
AB  - Taxus plant suspension cell cultures provide a sustainable source of paclitaxel
      (Taxol) for the treatment of many cancers. To develop an optimal bioprocess for
      paclitaxel supply, taxane biosynthetic pathway regulation must be better
      understood. Here we examine the expression profile of paclitaxel biosynthetic
      pathway genes by RNA gel blot analysis and RT-PCR in the Taxus cuspidata cell
      line P991 and compare with taxane metabolite levels. Upon methyl jasmonate (MJ)
      elicitation (100 microM), paclitaxel accumulates to 3.3 mg/L and cephalomannine
      to 2.2 mg/L 7 days after elicitation but neither are observed before this time.
      10-deacetylbaccatin III accumulates to 3.3 mg/L and baccatin III to 1.2 mg/L by
      day 7 after elicitation. The early pathway enzyme genes GGPPS, TASY, and T5alphaH
      are up-regulated by MJ elicitation within 6 h and continue through 24 h before
      their abundances decrease. This study reveals the preference for one side of the
      biosynthetic pathway branch in early taxane synthesis, where transcripts coding
      for TalphaH are abundant after elicitation with MJ but transcripts encoding the
      two enzymes for the alternative branch (TDAT and T10betaH) are not highly
      expressed following elicitation. Transcripts encoding the enzymes DBBT and DBAT
      are up-regulated upon MJ elicitation. Their products, 10-deacetylbaccatin III and
      baccatin III, respectively, accumulate within 6 h of the initial increase in
      transcript abundance. Importantly, the steady-state levels of the two terminal
      enzyme transcripts (BAPT and DBTNBT) are much lower than transcripts of early
      pathway steps. These are potential steps in the pathway for targeted metabolic
      engineering to increase accumulation of paclitaxel in suspension cell culture.

PMID- 16793303
TI  - A three-level problem-centric strategy for selecting NMR precursor labeling and
      analytes.
AB  - We have developed a sequential set of computational screens that may prove useful
      for evaluating analyte sets for their ability to accurately report on metabolic
      fluxes. The methodology is problem-centric in that the screens are used in the
      context of a particular metabolic engineering problem. That is, flux bounds and
      alternative flux routings are first identified for a particular problem, and then
      the information is used to inform the design of nuclear magnetic resonance (NMR)
      experiments. After obtaining the flux bounds via MILP, analytes are first
      screened for whether the predicted NMR spectra associated with various analytes
      can differentiate between different extreme point (or linear combinations of
      extreme point) flux solutions. The second screen entails determining whether the
      analytes provide unique flux values or multiple flux solutions. Finally, the
      economics associated with using different analytes is considered in order to
      further refine the analyte selection process in terms of an overall utility
      index, where the index summarizes the cost-benefit attributes by quantifying
      benefit (contrast power) per cost (e.g., NMR instrument time required). We also
      demonstrate the use of an alternative strategy, the Analytical Hierarchy Process,
      for ranking analytes based on the individual experimentalist's-generated weights
      assigned for the relative value of flux scenario contrast, unique inversion of
      NMR data to fluxes, etc.

PMID- 16793304
TI  - Counteracting apoptosis and necrosis with hypoxia responsive expression of Bcl
      2Delta.
AB  - In the encapsulated environment of biohybrid artificial organs, cells often
      encounter a deficiency in oxygen, which lead to apoptosis, necrosis, and lost of
      productivity. Two vectors with constitutive CMV promoters were constructed to
      examine the ability of Bcl-2Delta to help C2C12 mouse myoblasts maintain
      exogenous protein production under hypoxia. Two additional vectors with hypoxia
      inducible promoters (5HRE) that switched on Bcl-2Delta expression based on low
      oxygen levels (0.0%, 0.5%, 1.0%, 2.0%, 5.0%, or 21.0%) were tested for protein
      productivity and protection against hypoxic stresses. A yellow fluorescent
      protein was used as a model protein in all vector constructs. C2C12 cells with
      Bcl-2Delta consistently produced more protein regardless of the oxygen level or
      promoter used. Cells utilizing the 5HRE rather than the CMV promoter showed an
      increased level of protein production as the oxygen was decreased. Among the
      cells with 5HRE promoters, the presence of Bcl-2Delta also increased viability
      and decreased apoptosis.

PMID- 16793305
TI  - The first outbreak of acute diarrhea due to a pandemic strain of Vibrio
      parahaemolyticus O3:K6 in Kolkata, India.

PMID- 16793306
TI  - Molecular epidemiology of vancomycin-resistant Enterococcus faecium in Argentina.
AB  - OBJECTIVE: To characterize the mechanism of glycopeptide resistance and to
      determine the genetic relatedness among strains by pulsed-field gel
      electrophoresis (PFGE) in vancomycin-resistant Enterococcus faecium from
      Argentina. MATERIALS AND METHODS: A total of 189 vancomycin-resistant single
      patient isolates of Enterococcus faecium recovered between January 1997 and
      December 2000 from 30 hospitals in Argentina were studied. Minimum inhibitory
      concentrations were determined by the agar dilution method and van genes were
      detected by PCR. PFGE was used for molecular typing. RESULTS: All isolates except
      three (vanB) were of genotype vanA. For 189 vancomycin-resistant Enterococcus
      faecium, SmaI-PFGE indicated 35 clonal types. Most of the isolates (56%) belonged
      to the same clonal type 1, which was present in 19 hospitals and dominant in 17.
      CONCLUSIONS: The emergence of vancomycin-resistant Enterococcus faecium in
      Argentina seems to be related to the intra- and inter-hospital dissemination of
      an epidemic clone carrying the vanA element.

PMID- 16793307
TI  - Background demographics and risk behaviors of injecting drug users in Karachi,
      Pakistan.
AB  - OBJECTIVE: To find the prevalence of HIV infection and risk behaviors among
      injecting drug users (IDUs) in Karachi, Pakistan. DESIGN: A cross-sectional study
      of IDUs conducted in Karachi, Pakistan from February through June 1996. RESULTS:
      Of the 242 IDUs, 11 (4%) refused HIV testing. One (0.4%; 95% confidence interval
      (CI) = 0.37-0.48%) was HIV positive. All subjects were male. Over the past 6
      months 47% had engaged in receptive needle sharing, 38% had perceived a change in
      their social network, 22% had had sexual intercourse, of whom only 7% always used
      condoms, and none had washed their needles with bleach. Younger age (28 vs. 31
      years; p = 0.01), younger age at first injection (25 vs. 28 years; p = 0.001),
      fewer years of schooling (3 vs. 5 years; p = 0.001), lower monthly income (70
      dollars vs. 80 dollars; p = 0.03), inhaling fumes of heroin from a foil in the
      year before injecting (OR = 4.8; CI = 2.2-10.3), injecting first time with heroin
      (OR = 3.6; CI = 1.2-12.6), having a temporary job (OR = 2.5; CI = 1.2-5.2), and a
      perceived change in one's social network (OR = 4.4; CI = 2.4-7.9) were all
      associated with receptive needle sharing. IDUs who knew about HIV spread through
      contaminated needles were less likely to share (OR = 0.4; CI 0.2-0.8). In the
      final logistic regression model receptive needle sharing was associated with
      inhaling of fumes of heroin on a foil in the year prior to injecting (adjusted OR
      = 5.6; CI = 2.6-12.0), a perceived change in one's social network (adjusted OR =
      4.0; CI = 2.2-7.4), and inversely associated with age at first time of injection
      (beta = -0.07; p = 0.002). CONCLUSION: Background HIV prevalence was low among
      IDUs in Karachi despite high-risk behavior in 1996. In order to control HIV
      transmission among IDUs in Pakistan, continual HIV surveillance with well
      coordinated and effective HIV risk reduction, and drug demand reduction programs
      need to be implemented among drug users.

PMID- 16793308
TI  - Structural and functional insights into the assembly of type 1 pili from
      Escherichia coli.
AB  - Type 1 pili are filamentous protein complexes that are anchored to the outer
      membrane of uropathogenic Escherichia coli and mediate bacterial adhesion to the
      surface of urinary epithelium cells. We review here the current status of
      structural and functional studies on the assembly of type 1 pili.

PMID- 16793309
TI  - Hantavirus cardiopulmonary syndrome: immune response and pathogenesis.
AB  - Hantaviruses are emerging viruses in the Americas that cause cardiopulmonary
      syndrome with high lethality. The intense cellular immune response to hantavirus
      alters normal endothelial cell barrier functions and seems to be harmful to the
      host. On the other hand, the humoral immune response seems to be essential for
      recovery from infection.

PMID- 16793310
TI  - Differential expression of Cryptosporidium parvum genes encoding sporozoite
      surface antigens in infected HCT-8 host cells.
AB  - Intracellular replication of Cryptosporidium parvum (Apicomplexa) involves the
      generation of several asexual and sexual forms of the parasite. During the stage
      conversions, complex mechanisms lead to differential structural and functional
      properties of the parasite. These require a well tuned gene transcription
      machinery. For the first time the gene expression of four surface proteins of C.
      parvum sporozoites, CP15, CP17, P23, and GP900 were analysed in parallel by
      reverse transcription polymerase chain reaction. In addition, CP17 and P23
      antigens were detected in infected host cells by immunofluorescence using
      antisera raised against recombinant forms of the proteins. The results show that
      expression of each gene follows a unique time schedule during intracellular
      development, suggesting that the functions of these proteins during the life
      cycle are not restricted to the invasive stages.

PMID- 16793311
TI  - Enhanced susceptibility of multidrug resistant strains of Mycobacterium
      tuberculosis to granulysin peptides correlates with a reduced fitness phenotype.
AB  - Previously it was shown that the antimicrobial protein granulysin possesses
      potent membranolytic activity against Mycobacterium tuberculosis. Here we
      demonstrate that granF2 and G13, which are two short synthetic peptides derived
      from granulysin, inhibited the in vitro growth of clinical isolates of both
      multidrug resistant and drug susceptible strains of M. tuberculosis. Importantly,
      a particularly high activity against multidrug resistant M. tuberculosis
      correlated with a reduced growth rate compared to drug susceptible strains. A
      synergistic antibacterial effect of granF2 was further observed in combination
      with ethambutol, a compound with a documented effect on cell wall permeability.
      This finding suggests that granF2 and ethambutol exert their functions at
      different levels of the mycobacterial surface. Upon infection of macrophages in
      vitro, granF2 but not G13 efficiently reduced the intracellular growth of
      multidrug resistant M. tuberculosis in the presence of the pore-forming protein
      streptolysin O. The apoptotic function of granF2 apparently promoted destruction
      of host cells whereby the peptide gained access to and killed intracellular
      bacteria. Thus, a cost of resistance and a subsequent reduced fitness, measured
      as decreased growth among multidrug resistant strains of M. tuberculosis, could
      be associated with increased susceptibility to natural immune defense mechanisms,
      such as antimicrobial peptides of granulysin. However, a robust cell wall and the
      membrane of cells still provide physical shelter for the bacteria that may spare
      sensitive M. tuberculosis stains from being killed.

PMID- 16793312
TI  - An SopB-mediated immune escape mechanism of Salmonella enterica can be subverted
      to optimize the performance of live attenuated vaccine carrier strains.
AB  - Salmonellae have evolved several mechanisms to evade host clearance. Here, we
      describe the influence on bacterial immune escape of the effector protein SopB,
      which is translocated into the cytosol through a type III secretion system. Wild
      type bacteria, as well as the sseC and aroA attenuated mutants exerted a stronger
      cytotoxic effect on dendritic cells (DC) than their SopB-deficient derivatives.
      Cells infected with the double sseC sopB, phoP sopB and aroA sopB mutants also
      exhibited higher expression of MHC, CD80, CD86 and CD54 molecules, and showed a
      stronger capacity to process and present an I-E(d)-restricted epitope from the
      influenza hemagglutinin (HA) to CD4+ cells from TCR-HA transgenic mice in vitro.
      The incorporation of an additional mutation into the sopB locus of the attenuated
      sseC, phoP and aroA mutants resulted in the stimulation of improved humoral and
      cellular immune responses following oral vaccination. The obtained results define
      a new potential immune escape strategy of this important pathogen, and also
      demonstrate that this mechanism can be subverted to optimize the immune responses
      elicited using Salmonella as a live vaccine carrier.

PMID- 16793313
TI  - Involvement of Ssp-4-related carbohydrate epitopes in mammalian cell invasion by
      Trypanosoma cruzi amastigotes.
AB  - We examined whether the expression of Ssp-4-related carbohydrate epitopes defined
      by monoclonal antibodies 1D9 and 2B7 was related to cell invasion by Trypanosoma
      cruzi amastigotes from different isolates and whether the highest expression of
      the epitope defined by MAb 1D9 would confer greater infectivity. Confocal
      microscopy showed that both epitopes localize to the membrane of amastigotes from
      569, 588, 573, 587 and SC2005 isolates, similar to the G isolate, whereas the CL
      isolate showed a punctate and diffuse staining. Flow cytometry revealed inter-
      and intra-isolate variable expression of these epitopes. Apart from the lower
      expression of MAb 2B7 epitope by intracellular amastigotes of the SC2005 isolate,
      amastigotes from chagasic patient isolates expressed both epitopes similar to the
      G isolate, in contrast to CL isolate, that showed lower expression of both
      epitopes. MAb 1D9 did not react with CL isolate on immunoblots and reacted poorly
      with 588 and 587 parasites. MAb 2B7 preferentially reacted with an epitope on an
      84 kDa component in G and 573 isolates. Invasion assays revealed that despite the
      fact that amastigotes from chagasic patient isolates displayed high levels of the
      epitope defined by MAb 1D9, only isolate 588 invaded host cells in levels
      comparable to that of isolate G. Both MAbs specifically inhibited cell invasion
      by G and 588, but not CL. These results suggested that the highest expression of
      MAb 1D9 epitope was not sufficient to confer higher infectivity on the isolate,
      and besides the two epitopes, other factors may modulate the invasiveness of
      extracellular amastigotes from the different isolates.

PMID- 16793315
TI  - Metal-metal oxide pH sensors for physiological application.
AB  - Metal-metal oxide electrodes provide robust and miniaturised pH sensors. Iridium
      oxide electrodes prepared by thermal oxidation and by anodisation are described
      and their relative merits discussed. The effects of chloride and protein
      adsorption on sensor performance are investigated using cyclic voltammetry and
      the mechanism by which Nafion membranes can stabilise sensor response is
      identified. Applications in cultured intervertebral disc are reported.

PMID- 16793314
TI  - Toxicological and histopathological analysis of a patient who died nine days
      after a single intravenous dose of methamphetamine: a case report.
AB  - A man in his late twenties collapsed shortly after intravenously injecting
      himself with methamphetamine (MA). He slipped into a deep coma and remained in
      this condition for 9 days, until his death. Autopsy revealed severe brain edema
      and localized subarachnoid hemorrhages in the cerebrum and cerebellum.
      Histopathological examination revealed myocardial necrosis in the left ventricle,
      rhabdomyolysis and bronchopneumonia. Blood derived from the cadaver was found to
      have high levels of blood urea nitrogen and creatinine, suggesting he experienced
      acute renal failure probably due to rhabdomyolysis. Most of the postmortem
      findings were consistent with MA poisoning. The patient's bronchopneumonia may
      have represented a hypostatic pneumonia that developed as a result of his deep
      coma. While the patient's brain edema, myocardial necrosis and rhabdomyolysis
      were diagnosed soon after admission, his bronchopneumonia and acute renal failure
      only occurred 6 and 8 days later, respectively. Although MA was not detected in
      the cadaver's blood, urine or liver, analysis of the decedent's hair using gas
      chromatography-mass spectrometry confirmed its presence at a concentration of 1.1
      ng/mg. Based on these findings, we concluded that the patient's cause of death
      was multiorganopathy resulting from MA poisoning. This case suggests that the
      postmortem diagnosis of MA poisoning in patients who survive for relatively
      longer periods after drug injection should include toxicological hair analysis in
      combination with histopathological and postmortem physiochemical examination.

PMID- 16793316
TI  - Tremor magnitude: a single index to assess writing and drawing in essential
      tremor.
AB  - Hand tremor often causes disability in patients with essential tremor (ET). Aim
      of the study was to investigate whether tremor magnitude, a new single
      quantitative score obtained from digital tablet recordings of writing and
      drawing, is able to adequately reflect disability in ET patients. Mean tremor
      magnitude values showed significant difference between 14 ET patients and 14
      healthy age matched controls (p<0.0001). The tremor magnitude values showed
      significant correlation with standard methods of clinical assessment (p<0.01). We
      present tremor magnitude as an index that reflects disability resulting from
      tremor and can help to evaluate ET.

PMID- 16793317
TI  - Are the insular cortex and cortisol implicated in Parkinsonian features?
AB  - Recent studies implicate insular cortex and the hormone cortisol in Parkinsonian
      features. Dopaminergic alterations at the level of the insula may be involved in
      changes in personality (i.e. novelty seeking) and symptoms of hemispatial
      neglect. I discuss this evidence and suggest that attention in future research to
      a possible role of the insula and of cortisol in Parkinsonian features may yield
      valuable information regarding Parkinson's disease.

PMID- 16793318
TI  - Relationship between event-related potentials and frontal-subcortical dysfunction
      in Parkinson's disease.
AB  - Cognitive impairment in Parkinson's disease (PD) has been determined to be due to
      the interruption of frontal-subcortical neural circuits. To evaluate which kind
      of frontal-subcortical dysfunction may be present and the relationship of this
      dysfunction with P300 in PD patients, non-demented PD patients and controls were
      rendered for comprehensive Frontal Test Battery and P300 assessments. PD patients
      manifested significantly with frontal dysfunction and revealed a good correlation
      between P300 and executive dysfunction. We conclude that PD patients may manifest
      with cognitive impairment related to frontal dysfunction, and P300 may be an
      indicator reflecting the evolution of dysexecutive syndrome.

PMID- 16793319
TI  - Molecular pathogenesis of Parkinson's disease: identification of mutations in the
      Parkin gene in Indian patients.
AB  - Parkinson's disease (PD), the second most common neurodegenerative disorder,
      affects at least 1% of the population over the age of 50. However, very little
      information is available regarding the molecular basis of PD among Indians. Since
      the largest number of mutations have been detected in the Parkin gene among all
      known PD loci, we aim to use Parkin as the candidate gene to assess its role in
      PD-related pathogenesis in Indian patients. A total of 138 PD patients, with the
      mean age of onset being 47+/-14 (age range, 5-77 years), and 100 controls were
      recruited for the study from eastern India. Parkin mutations were detected by
      amplification of exons of the gene along with the flanking splice junctions by
      polymerase chain reaction, single-stranded conformation polymorphism and DNA
      sequencing. A total of 18 nucleotide variants including six novel changes were
      detected. These include five missense mutations (Gln34Arg, Arg42Cys, Arg42His,
      Tyr143Cys and Arg334Cys) detected in eight patients in heterozygous condition and
      a homozygous deletion encompassing exons 3 and 4 in two sibs affected with PD.
      Clinical features of the Parkin mutants were compared. Among eastern Indian PD
      patients, mutation in Parkin was identified in 7.24% cases.

PMID- 16793320
TI  - The SCA17 phenotype can include features of MSA-C, PSP and cognitive impairment.
AB  - Spinocerebellar ataxia (SCA) 17 is a dominant neurodegenerative disorder
      characterized by ataxia, cognitive decline, dystonia, and parkinsonism. The
      disease is caused by unstable cytosine-adenine-guanine (CAG) trinucleotide
      expansion mutation coding for polyglutamine tracts in the TATA box-binding
      protein (TBP), a general transcription initiation factor. Herein, we report a
      SCA17 case with a phenotype not previously reported, which consisted of
      progressive ataxia, autonomic dysfunction, parkinsonism, supranuclear palsy and
      cognitive impairment. Cerebrospinal fluid study and 18F-dopa PET scanning
      demonstrated dopamine deficiency and nigrostrital degeneration. This case expands
      the current phenotype associated with SCA17. SCA17 should be considered in the
      differential diagnosis of cases resembling multiple system atrophy, especially
      those with atypical features.

PMID- 16793321
TI  - Cyclic AMP stimulates MEG3 gene expression in cells through a cAMP-response
      element (CRE) in the MEG3 proximal promoter region.
AB  - MEG3 is a human maternally expressed gene that potentially acts as a non-coding
      RNA. Our laboratory found that a cDNA isoform of MEG3, MEG3a, inhibits cell
      proliferation. MEG3 is highly expressed in the normal human pituitary but not
      expressed in clinically non-functioning pituitary tumors, suggesting that this
      imprinted gene may be involved in pituitary tumorigenesis. Previously we
      demonstrated that hypermethylation of the MEG3 promoter region is associated with
      the loss of MEG3 expression in pituitary tumors, potentially by blocking the
      binding of transcription factors to their cis-elements. To further investigate
      the cis- and trans-factors that are important for the regulation of MEG3, we have
      characterized the human MEG3 promoter. A single transcription initiation site was
      identified by 5' RACE. Up to 5kb of the 5'-flanking region of MEG3 gene was
      cloned into a reporter plasmid. Deletion and mutation analysis suggest that a
      cAMP response element (CRE), located between -69 and -49 of the MEG3 proximal
      promoter region, is critical for promoter activity. Consistent with this finding,
      Northern blot analysis demonstrate that elevated intracellular cAMP levels
      stimulate MEG3 expression in human fibroblasts in culture. Furthermore, gel
      shifting, ChIP analysis, and co-transfection experiments show that CREB directly
      binds to the CRE site and stimulates MEG3 promoter activity. Therefore, MEG3 is a
      downstream target gene of cAMP. Together with the anti-proliferative function of
      cAMP, our data suggest that MEG3 may interact with the cAMP-dependent signaling
      pathway to be involved in the control of cell proliferation and other cAMP
      related physiological functions.

PMID- 16793322
TI  - Alternative pathways of NF-kappaB activation: a double-edged sword in health and
      disease.
AB  - While the classical pathway of NF-kappaB activation plays critical roles in a
      wide range of biological processes, the more recently described "non-canonical"
      NF-kappaB pathway has important but more restricted roles in both normal and
      pathological processes. The non-canonical NF-kappaB pathway, based on processing
      of the nf-kappab2 gene product p100 to generate p52, appears to be involved in B
      cell maturation and lymphoid development. Deregulated activation of this pathway
      has been observed in a variety of malignant and autoimmune diseases, thus
      inhibitors that specifically target p100 processing might be predicted to have
      potential roles as immunomodulators and in the therapy of malignant diseases. We
      review current understandings of NF-kappaB activation, particularly the
      mechanisms of p100 processing under both physiological and pathological
      conditions.

PMID- 16793323
TI  - Bayesian theories of conditioning in a changing world.
AB  - The recent flowering of Bayesian approaches invites the re-examination of classic
      issues in behavior, even in areas as venerable as Pavlovian conditioning. A
      statistical account can offer a new, principled interpretation of behavior, and
      previous experiments and theories can inform many unexplored aspects of the
      Bayesian enterprise. Here we consider one such issue: the finding that surprising
      events provoke animals to learn faster. We suggest that, in a statistical account
      of conditioning, surprise signals change and therefore uncertainty and the need
      for new learning. We discuss inference in a world that changes and show how
      experimental results involving surprise can be interpreted from this perspective,
      and also how, thus understood, these phenomena help constrain statistical
      theories of animal and human learning.

PMID- 16793324
TI  - Probabilistic inference in human semantic memory.
AB  - The idea of viewing human cognition as a rational solution to computational
      problems posed by the environment has influenced several recent theories of human
      memory. The first rational models of memory demonstrated that human memory seems
      to be remarkably well adapted to environmental statistics but made only minimal
      assumptions about the form of the environmental information represented in
      memory. Recently, several probabilistic methods for representing the latent
      semantic structure of language have been developed, drawing on research in
      computer science, statistics and computational linguistics. These methods provide
      a means of extending rational models of memory retrieval to linguistic stimuli,
      and a way to explore the influence of the statistics of language on human memory.

PMID- 16793325
TI  - Make mild moments memorable: add a little arousal.
AB  - In a recent paper Anderson and colleagues reported that emotionally arousing
      stimuli enhance long-term memory of immediately preceding neutral stimuli. The
      findings fit well with the perseveration-consolidation hypothesis and with
      extensive evidence from both human and animal studies indicating that arousal
      induced modulation of memory is mediated by beta-noradrenergic activation of the
      amygdala.

PMID- 16793326
TI  - High content cellular screening.
AB  - Over the past few years, high content screening has firmly established itself as
      a high-throughput technology for the analysis of microscopy-based cellular
      assays. In particular, it has opened new areas of cell biology for the large
      scale analysis of cellular phenotypes and has enabled the application of
      increasingly sophisticated assays for large-scale genetic and compound screening,
      benefiting both the academic and pharmaceutical research environment.

PMID- 16793327
TI  - Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant
      decrease in testosterone and increase in lactate dehydrogenase concentration in
      the testis.
AB  - Treatment of cancers with cytotoxic agents such as alkylating drugs often, but
      not always results in transient to permanent testicular dysfunction. The present
      study was planned to investigate the effects of dacarbazine [5-(3,3
      dimethyltriazeno) imidazole-4-carboxamide] on testicular function in mice. Swiss
      albino mice (9-12 weeks old) were treated with 0, 5, 25, 50, or 100mg/kg body
      weight/day dacarbazine (i.p.) for 5 days at intervals of 24h between treatments.
      Mice were sacrificed on days 7, 14, 21, 28, 35, 49, and 70 after the last
      treatment (6 mice/dose/sample time), and the epididymal sperm count, sperm
      motility, sperm morphology, testicular histopathology (qualitative
      histopathology, seminiferous tubular diameter and epithelial height), and intra
      testicular levels of testosterone and lactate dehydrogenase were assessed.
      Dacarbazine decreased the body weight only on day 28 at 25mg/kg dose-level, but
      increased the paired testes weights at 50mg/kg on day 7, at 25-100mg/kg on day
      14, and at 25 and 50mg/kg on day 21 (P<0.05-0.01; one-way ANOVA and Bonferroni's
      post hoc test). The sperm count was decreased on all sampling days except at 5
      and 25mg/kg dose-levels on day 70, but with severe oligospermia on days 28 and 35
      (P<0.05-0.001). The sperm motility was decreased at 100mg/kg on days 14 and 21,
      at 5, 25, and 100mg/kg on day 28, and at all dose-levels on day 35 (P<0.05
      0.001). Dacarbazine induced both head and tail abnormalities and some sperms with
      cytoplasmic droplets, but significant increase was seen in all dose groups on
      days 14 and 21, and at 100mg/kg dose-level on day 35. Drug-induced epithelial
      sloughing was seen on days 14-35 and other histopathological changes observed
      were vacuoles and abnormal cells. The STD was increased at 25-100mg/kg on day 7,
      at all dose-levels on day 14, at 50-100mg/kg on days 21 and 28, but without any
      effects on days 35-70 (P<0.05-0.001), and the tubular lumen was found dilated.
      The SE was increased on days 7, 21 and 28 at 100mg/kg and on day 14 at 50
      100mg/kg. Dacarbazine reduced the intra-testicular testosterone level at 100mg/kg
      on day 7, at 5, 50 and 100mg/kg on day 14, at all dose-levels on days 21, 28, and
      35, and at 50mg/kg on day 49 (P<0.05-0.001). The intra-testicular lactate
      dehydrogenase concentration increased at all dose-levels up to day 35, but
      without any effect on days 49 and 70 (P<0.05-0.001). There was no particular dose
      response of dacarbazine on any parameters tested. The sperm count (except on day
      7-positive correlation; Pearson product moment correlation) or sperm motility did
      not have any relation but increase in abnormal sperms showed negative correlation
      with decrease in testosterone level on days 7, 21 and 28. Decrease in sperm count
      was in negative correlation on days 14 and 35, and increase in abnormal sperms
      showed positive correlation on day 35 with increase in LDH level. Finally, the
      decrease in sperm motility had no correlation with increase in abnormal sperm
      shapes. We conclude that dacarbazine is genotoxic and cytotoxic to the mouse
      testis in a transient fashion, and these effects are exerted along with decrease
      in testosterone and increase in lactate dehydrogenase levels in the testis.

PMID- 16793328
TI  - Induction of specific immune responses against the Plasmodium vivax liver-stage
      via in vitro activation by dendritic cells.
AB  - Due to chronic morbidity, the risk of increasing drug resistance and the
      existence of the hypnozoite stage in Plasmodium vivax malaria, there is a need to
      find out how hosts develop immunity to compromise the malaria parasites. Here we
      focused on an in vitro model for immunotherapy and vaccine development.
      Immunosuppressive mechanisms in malaria include inhibition of T cell response and
      suppression of dendritic cell function. Using in vitro activation of lymphocytes
      by malaria antigen-pulsed dendritic cells could overcome the limitation of
      antigen presentation during acute infections. Here we showed that the sporozoite
      pulsed dendritic cell could elicit cytotoxicity against liver stage of P. vivax.
      Analysis using immunophenotypic markers showed maturation of the dendritic cells
      and stimulation of cytotoxic T cells. Functional assay of the in vitro-activated
      cytotoxic T cells showed enhancement of specific killing of the P. vivax
      exoerythrocytic stages within infected hepatocytes. This model may be useful for
      vaccine development against human malaria.

PMID- 16793329
TI  - An investigation into health informatics and related standards in China.
AB  - OBJECTIVE: To describe the current status of and future plans for health
      informatics and related standards in China and analyze the problems raised in the
      process of standardization for health informatics. METHODS: Data were collected
      through investigation and interviews, complemented by a comprehensive review of
      relevant literatures and regulations/law documents about health informatics and
      related standards in China. RESULTS: Health informatics has been greatly
      developed in China. Significant resources were committed to construct and improve
      the health information system. Approximately 35-40% of hospitals have constructed
      hospital information system. Over 80% of medical organizations above the
      county/district level, 27% of town level hospitals and all CDC above the
      county/district level can transmit real-time epidemic situation reporting through
      public health information system. However, lack of standards became a bottleneck
      to utilize and improve health informatics. China has adopted some vocabulary,
      classification, coding standards and message standards. Moreover, several
      national standardization actions for health informatics have been taken. In the
      process of standardization, the main barriers consist of financial, technical,
      cultural and language problems, legal and ethical concerns and others.
      CONCLUSIONS: Informatics has the potential to play an important role in China's
      healthcare reform process and standards are the basis for the information sharing
      and interoperability. Governments and partners of health informatics have
      realized the importance of standards and taken the initiatives in trying to solve
      the problem of lacking standards, but much work still needs to be done.

PMID- 16793330
TI  - Categorizing the unintended sociotechnical consequences of computerized provider
      order entry.
AB  - OBJECTIVE: To describe the kinds of unintended consequences related to the
      implementation of computerized provider order entry (CPOE) in the outpatient
      setting. DESIGN: Ethnographic and interview data were collected by an
      interdisciplinary team over a 7 month period at four clinics. MEASUREMENTS:
      Instances of unintended consequences were categorized using an expanded Diffusion
      of Innovations theory framework. RESULTS: The framework was clarified and
      expanded. There are both desirable and undesirable unintended consequences, and
      they can be either direct or indirect, but there are also many consequences that
      are not clearly either desirable or undesirable or may even be both, depending on
      one's perspective. The undesirable consequences include error and security
      concerns and issues related to alerts, workflow, ergonomics, interpersonal
      relations, and reimplementations. CONCLUSION: Consequences of implementing and
      reimplementing clinical systems are complex. The expanded Diffusion of
      Innovations theory framework is a useful tool for analyzing such consequences.

PMID- 16793331
TI  - What is the role of lamellae in solubilizing of biliary cholesterol in hepatic
      bile?

PMID- 16793332
TI  - Molecular and serological evidence of the epidemiological association of HPV 13
      with focal epithelial hyperplasia: a case-control study.
AB  - BACKGROUND: Focal epithelial hyperplasia is a benign proliferative condition that
      is more frequently found in children of certain ethnic groups. Human
      papillomavirus 13 and 32 DNA has been consistently detected in these lesions.
      OBJECTIVE: To demonstrate the epidemiological association of HPV 13 with FEH in
      the Embera-Chami community of Antioquia, Colombia. METHODS: A population-based,
      case-control study was conducted. One hundred and thirty-eight children were
      screened and 17 clinical and histologically-confirmed cases were sex and age
      matched with 27 controls. Biopsies from FEH lesions and mouth washes from
      controls were obtained for DNA analysis. HPV 13 DNA was identified using a
      previously described type-specific PCR test. HPV 13 VLPs were produced by cloning
      of L1 from the HPV 13 cloned genome and seroreactivity against HPV 13 VLPs of
      sera from cases and controls were evaluated by ELISA. RESULTS: Among the whole
      population the prevalence of FEH was 13%. One-hundred-percent of the cases and
      29.6% of the controls were HPV 13 positive. There was a significant difference in
      HPV DNA status between cases and controls (one-tailed Fisher exact test:
      P<0.0001). Antibodies against HPV 13 VLPs were found in 58.8% of cases and in
      33.3% of controls, this difference was not statistically significant (P=0.089
      Fisher exact test). However, the median of the ODs of the ELISA positive sera of
      the cases was 0.596 (interquartile range: 0.5075-0.8245) versus 0.452
      (interquartile range: 0.337-0.479) in the controls and this was significantly
      different (P=0.0041 Man-Whitney test). CONCLUSIONS: We demonstrated a risk for
      association of FEH with infection with HPV 13. The higher level of antibodies
      against HPV 13 VLPs in cases may suggest the requirement of higher viral load or
      viral persistence for disease development.

PMID- 16793333
TI  - Plastic changes in the human H-reflex pathway at rest following skillful cycling
      training.
AB  - OBJECTIVE: The spinal cord is capable of activity-dependent plasticity, but the
      extent of its participation in human motor learning is not known. Here, we tested
      the hypothesis that acquisition of a locomotor-related skill modulates the
      pathway of the H-reflex, a measure of spinal cord excitability that is
      susceptible to plastic changes. METHODS: Subjects were tested on their ability to
      establish a constant cycling speed on a recumbent bike despite frequent changes
      in pedal resistance. The coefficient of variation of speed (CV(speed)) measured
      their ability to acquire this skill (decreasing CV(speed) with training reflects
      performance improvements). Soleus H-reflexes were taken at rest before and after
      cycling. RESULTS: Ability to establish a target speed increased and H-reflex size
      decreased more after cycling training involving frequent changes in pedal
      resistance that required calibrated locomotor compensatory action than with
      training involving constant pedal resistances and lesser compensation. The degree
      of performance improvement correlated with the reduction in the amplitude of the
      H-reflex. CONCLUSIONS: Skillful establishment of a constant cycling speed despite
      changing pedal resistances is associated with persistent modulation of activity
      in spinal pathways. SIGNIFICANCE: Recalibration of activity in the H-reflex
      pathway may be part of the control strategy required for locomotor-related skill
      acquisition.

PMID- 16793334
TI  - Detection of signals in modulated and unmodulated noise observed using auditory
      evoked potentials.
AB  - OBJECTIVE: To investigate a neurophysiological correlate of the perceptual
      enhancement of noise-masked sounds when the masking frequencies have a wide
      spectral bandwidth and are coherently amplitude-modulated. METHODS: Auditory
      evoked potentials were recorded to 1 kHz tones (200 ms, 61 dBSPL, SOA 3s)
      occurring in silence or with 80 dB masking noise, which was either wide-band or
      narrow-band and either unmodulated or 100% amplitude-modulated by a 17.5 Hz
      square-wave. In a second study, the tones were timed to coincide alternately with
      the rise and fall of the masker envelope. RESULTS: N1 and P2 potentials recorded
      to the unmasked tones were abolished in the presence of the unmodulated masker,
      but were elicited again with lower amplitude and longer latency when the masker
      was modulated. No significant effect of the masker bandwidth was observed.
      Latencies were strongly determined by whether the tones coincided with the rise
      or fall of the masker envelope, indicating that the responses were only evoked
      when the instantaneous noise level was low. CONCLUSIONS: The findings demonstrate
      partial correspondence to the threshold reduction to similar stimuli seen in
      comodulation masking release (CMR). The dependence of latencies on the phase of
      the masker envelope is consistent with the 'dip-listening' model of CMR.
      SIGNIFICANCE: Under these conditions the N1/P2 complex can be viewed as a
      possible neurophysiological correlate of perceptual CMR.

PMID- 16793335
TI  - Corticomotoneuronal dysfunction in ALS patients with different SOD1 mutations.
AB  - OBJECTIVE: To examine corticomotoneuronal function in amyotrophic lateral
      sclerosis (ALS) patients carrying superoxide dismutase 1 (SOD1) mutations using
      peristimulus time histograms (PSTH). METHODS: Six I113T, 3 A4V, one G41D and one
      G114A patient were studied along with 21 healthy control subjects. Analyses
      included comparison with previously reported data from 8 D90A homozygous and 12
      sporadic ALS (SALS) patients examined by the authors using identical methodology.
      RESULTS: Cortical threshold was significantly reduced in A4V patients (41.3%)
      compared to I113T (58%), SALS (57%) and D90A (71%) patients, as well as healthy
      controls (49.7%). Estimated excitatory postsynaptic potentials (EPSPs) were
      significantly larger in A4V patients (4.39 mV) compared to healthy controls (2.95
      mV), I113T (2.71 mV) and SALS (2.39 mV) patients. Clinical features and PSTH
      parameters in I113T were similar to SALS, however, PSTH primary peaks (PP) were
      significantly more dispersed, 9.5 ms compared to 4ms in SALS. PSTHs from single
      G41D and G114A patients were unremarkable, apart from large EPSP amplitudes in
      the G114A patient. CONCLUSIONS: ALS patients with A4V and I113T SOD1 mutations
      have distinctive corticomotoneuronal changes that are different from those in
      D90A homozygous and SALS patients. SIGNIFICANCE: PSTH studies should be
      considered for future in vivo studies of SOD1 pathophysiology in ALS.

PMID- 16793336
TI  - Electroencephalographic recording during transcranial magnetic stimulation in
      humans and animals.
AB  - OBJECTIVE: We report on the development of an EEG recording system, comprised of
      electrodes and amplifiers that are compatible with TMS (single and rapid-rate) in
      both human and animal studies. METHODS: We assembled a versatile multi-channel
      EEG recording system consisting of: (1) two types of electrodes that are safe
      during TMS or rTMS. (2) Low slew-rate EEG amplifiers that recover within a few
      milliseconds after the application of TMS pulses. RESULTS: The two electrode
      types: (a) a conductive-plastic surface electrode with a conductive-silver epoxy
      coat and (b) a subdermal silver wire electrode (SWE) are compatible to TMS
      pulses. The amplifiers recover within 30 ms, so that the EEG can be viewed
      online, essentially without interruption and/or blocking or excessive artifact.
      CONCLUSIONS: Our TMS compatible electrode and EEG recording system allows safe
      and online viewing/recording of the subject's (human or animal) EEG/EP during
      experiments or studies involving TMS or rTMS applications. The TMS compatible
      electrode/amplifier system can be used with any EEG recording instrument.
      SIGNIFICANCE: A simple recording technique coupled with new electrodes permit
      safe and readable EEG records during TMS in humans and animals. Such online
      monitoring of the EEG would allow control of TMS/rTMS parameters based on EEG
      activity.

PMID- 16793337
TI  - Quantitative EEG in low-IQ children with attention-deficit/hyperactivity
      disorder.
AB  - OBJECTIVE: This study investigated EEG differences between children with
      attention-deficit/hyperactivity disorder (AD/HD) and matched control subjects,
      with either normal or low IQs. METHODS: Twenty normal-IQ and 20 low-IQ children
      with AD/HD, and 40 age-, IQ- and sex-matched control subjects participated in
      this study. EEG was recorded from 21 sites during an eyes-closed resting
      condition and Fourier transformed to provide estimates for total power, and
      absolute and relative power in the delta, theta, alpha and beta bands. RESULTS:
      Children with AD/HD had increased theta activity with decreased levels of alpha
      and beta activity compared to control subjects. IQ was not found to impact on the
      EEG. No significant differences were found between subjects with normal and low
      IQs, with the low- and high-IQ AD/HD groups having similar EEG profiles.
      CONCLUSIONS: Low-IQ children with AD/HD have similar EEG abnormalities to those
      with normal IQs, and IQ does not appear to impact on EEG power measures.
      SIGNIFICANCE: This is the first study to investigate EEG differences in low-IQ
      children with and without AD/HD.

PMID- 16793338
TI  - Motor cortical excitability studied with repetitive transcranial magnetic
      stimulation in patients with Huntington's disease.
AB  - OBJECTIVE: TMS techniques have provided controversial information on motor
      cortical function in Huntington's disease (HD). We investigated the excitability
      of motor cortex in patients with HD using repetitive transcranial magnetic
      stimulation (rTMS). METHODS: Eleven patients with HD, and 11 age-matched healthy
      subjects participated in the study. The clinical features of patients with HD
      were evaluated with the United Huntington's Disease Rating Scale (UHDRS). rTMS
      was delivered with a Magstim Repetitive Magnetic Stimulator through a figure-of-8
      coil placed over the motor area of the first dorsal interosseus (FDI) muscle.
      Trains of 10 stimuli were delivered at 5 Hz frequency and suprathreshold
      intensity (120% resting motor threshold) with the subjects at rest and during
      voluntary contraction of the target muscle. RESULTS: In healthy subjects at rest,
      rTMS produced motor evoked potentials (MEPs) that increased in amplitude over the
      course of the trains. Conversely in patients, rTMS left the MEP size almost
      unchanged. In both groups, during voluntary contraction rTMS increased the silent
      period (SP) duration. CONCLUSIONS: Because rTMS modulates motor cortical
      excitability by activating cortical excitatory and inhibitory interneurons these
      findings suggest that in patients with HD the excitability of facilitatory
      intracortical interneurones is decreased. SIGNIFICANCE: We suggest that depressed
      excitability of the motor cortex in patients with HD reflects a disease-related
      weakening of cortical facilitatory mechanisms.

PMID- 16793339
TI  - Top-down and bottom-up processes in the extrastriate cortex of cirrhotic
      patients: an ERP study.
AB  - OBJECTIVE: This study aims to evaluate the efficiency of top-down and bottom-up
      processes in the extrastriate cortex of cirrhotic patients without overt hepatic
      encephalopathy (HE). METHODS: Reaction times (RTs), accuracy and event-related
      potentials (ERPs) were recorded during the execution of a visual Simon task in 17
      cirrhotic patients and 10 healthy controls. Amplitude and latency of the P1 and
      N1 (indexes of bottom-up processes) and of the N2pc (index of top-down processes)
      were measured. RESULTS: Patients were slower than controls, and patients with
      minimal HE (MHE) were slower than patients without MHE. The distribution analysis
      of RTs showed that the Simon effect decays with slower RTs in all the groups and
      that the shape of the distribution was different in MHE patients. No differences
      were found between cirrhotic patients and controls for P1 and N1 amplitude and
      latency. In contrast, N2pc latency was delayed in cirrhotic patients compared to
      controls independently of MHE. CONCLUSIONS: In the extrastriate cortex of
      cirrhotic patients without HE, top-down processes are altered whereas bottom-up
      processes are preserved. SIGNIFICANCE: The analysis of exogenous and endogenous
      visual components of ERPs provides a model to study the functional dissociation
      between top-down and bottom-up processes inside the extrastriate cortex.

PMID- 16793340
TI  - Autonomic reactivity to sensory stimulation is related to consciousness level
      after severe traumatic brain injury.
AB  - OBJECTIVE: To examine changes in the activity of the autonomic nervous system
      (ANS) that are related to recovery to consciousness in the post-acute phase after
      severe traumatic brain injury (sTBI). METHODS: Skin conductance and heart rate
      reactivity to sensory stimulation were recorded every 2 weeks for an average
      period of 3.5 months in 16 adolescent patients, during the assessment of their
      level of consciousness (LoC), and their cognitive and functional behaviour.
      RESULTS: Both heart rate variability (HRV) and skin conductance level (SCL) in
      reaction to sensory stimulation changed with recovery to consciousness. Indices
      of HRV and SCL that represent sympathetic activity of the autonomic nervous
      system (ANS) increased with recovery, whereas indices that represent
      parasympathetic activity decreased. In addition, we observed an increase in
      sympathovagal balance of the ANS with recovery. CONCLUSIONS: Recovery to
      consciousness determined by clinical observation in sTBI in the post-acute phase
      is related to changes in SCL and HRV during sensory stimulation. ANS reactivity
      to environmental stimulation can therefore give objective supplementary
      information about the clinical state of sTBI patients, and can contribute to
      decision-making in the treatment policy of unresponsive patients. SIGNIFICANCE:
      These findings demonstrate that autonomic reactivity can be informative
      concerning how a severely damaged nervous system reacts to environmental
      stimulation and how, in a recovering nervous system, this reactivity changes.

PMID- 16793341
TI  - Blood lead levels among police officers in Lima and Callao, 2004.
AB  - Lead contamination is a public health problem of world-wide scope that negatively
      affects the health of especially women and children. Nevertheless, studies on
      lead contamination and its impact on health in Peru are limited. The objective of
      the present study was to determine blood lead levels (BLL) of traffic police
      officers in Lima and Callao compared with values in police officers working
      indoors and with data obtained in 1992. The study was performed in May-June 2004
      and included 52 traffic officers and 50 officers working in police stations in
      the north, center and east of Lima and Callao, Peru. Both groups were of similar
      age. The dependent variables were arterial blood pressure and BLL obtained in
      each officer. In addition a questionnaire was applied to evaluate risk factors
      for lead exposure. In 2004, the average BLL in traffic police officers was higher
      (44.7+/-6.1microg/l) than that of indoor police officers (39.3+/-8.2microg/l)
      (p=0.0001). However, none of the police officers had BLL of over 100microg/l. No
      differences were observed in the location of the residences of the participants
      and the respective traffic density. Those over 30 years of age had a higher risk
      of having a BLL over 42microg/l than younger officers (odds ratio (OR)=4.45).
      Traffic police officers had a higher risk of BLL >42microg/l (OR=4.80). Compared
      with data from 1992 obtained from the literature, an important reduction has been
      observed in 2004. This may be a consequence of the policy to eliminate leaded
      gasoline in Peru. However, it is still necessary to monitor this policy to ensure
      the elimination of lead in gasoline.

PMID- 16793342
TI  - Efficiency in endotoxin removal by a reprocessing protocol for electrophysiology
      catheters based on hydrogen peroxide plasma sterilization.
AB  - Electrophysiology and ablation cardiac catheters, which come in contact with
      blood during clinical use, are required to be non-pyrogenic (<20 endotoxin units
      (EU)/device). This study aimed to quantify the residual endotoxin load in
      reprocessed devices as a mandatory step to guarantee safe reuse. We monitored the
      pyrogenic status of the device (n=61) in three fundamental steps of the
      reprocessing protocol: after clinical use, after decontamination-cleaning
      treatments and after complete reprocessing, including sterilization by hydrogen
      peroxide gas plasma. Finally, a depyrogenation test was produced for evaluating
      the depyrogenation efficiency of the sole hydrogen peroxide sterilization
      treatment. Results showed that standard clinical use did not represent a source
      for endotoxin contamination, while the use of tap water and manual cleaning
      processing could increase the pyrogenic load in a significant way. The
      introduction of the sterilization by hydrogen peroxide gas plasma resulted in
      effective reduction of the endotoxin contamination and in safe reprocessing of 15
      of 15 clinically used catheters. In addition, tests conducted on in vitro spiked
      catheters showed that initial pyrogenic loads of 40, 80, 200EU/device were
      reduced to less than 11EU/device. Depyrogenation testing demonstrated efficiency
      in endotoxin reduction of more than 62 times (1.8log). These results show the
      determining role of hydrogen peroxide gas-plasma sterilization in the reduction
      of pyrogenic load on medical devices. Considering actual hygienic requirements at
      single-use device reprocessing, hydrogen peroxide gas-plasma sterilization can be
      considered as an efficient treatment at non-lumen cardiac electrophysiology
      catheter reprocessing.

PMID- 16793343
TI  - TGFbeta1, a "Jack of all trades": the link with pro-inflammatory IL-17-producing
      T cells.
AB  - Transforming growth factor (TGF)beta is most commonly considered an anti
      inflammatory cytokine, a view that clearly does not correlate with the recently
      described role for TGFbeta1 in the differentiation of T-helper (Th)17 cells, a
      novel, highly inflammatory T-cell subset that produces interleukin (IL)-17.
      However, these recent findings endorse earlier studies, pre-dating the discovery
      of Th17 cells, which described a seemingly paradoxical pro-inflammatory role of
      TGFbeta. In this article, we propose that the administration of neutralizing anti
      TGFbeta antibodies in target sites of chronic inflammation would ameliorate or
      abolish disease because this would limit the differentiation of Th17 cells. By
      contrast, similar interventions at mucosal sites, where Th17 cells seem to have a
      protective role, might exacerbate disease in experimental models of colitis. An
      excess production of Th17 cells in response to infection or trauma could result
      in leakage into peripheral tissues and cause autoimmune pathology.

PMID- 16793346
TI  - Resolution of decompensated cirrhosis from Wilson's disease with zinc
      monotherapy: a potential therapeutic option?
AB  - BACKGROUND & AIMS: Wilson's disease is a genetic autosomal-recessive copper
      deposition disorder often presenting with neurologic or hepatic symptoms. In
      cases of hepatic presentation, treatment usually is initiated with potentially
      toxic copper chelators, such as D-penicillamine or trientine. Although multiple
      studies have introduced zinc as a low-toxicity and low-cost Wilson's disease
      treatment, its use has been limited to adjunctive or single-agent maintenance
      options. In this report, we describe the use of zinc monotherapy in a patient
      with severe hepatic presentation of Wilson's disease. METHODS: Zinc has not been
      evaluated as a single-agent treatment option for active hepatic Wilson's disease.
      Zinc monotherapy was initiated for a single patient with fulminant hepatic
      failure caused by Wilson's disease while awaiting liver transplantation. RESULTS:
      Over a 1-year period with zinc monotherapy, this patient experienced
      normalization of hepatic synthetic function and resolution of hypoalbuminemia and
      coagulopathy. Clinical stabilization of variceal bleeds, ascites, and lower
      extremity edema also were observed. The patient is no longer a transplant
      candidate as a result of clinical recovery and improvement of Model for End-stage
      Liver Disease and Child-Turcotte-Pugh scores. CONCLUSIONS: This case highlights
      the potential use of zinc as a low-toxicity and low-cost single-agent treatment
      in severely decompensated hepatic Wilson's disease. Despite promising results in
      this case, further clinical evaluation will be necessary to assess fully the
      clinical efficacy of zinc monotherapy.

PMID- 16793345
TI  - Functional MRI reveals declined prefrontal cortex activation in patients with
      epilepsy on topiramate therapy.
AB  - Functional magnetic resonance imaging of covert word generation was used to
      examine brain activation abnormalities associated with topiramate-induced
      cognitive language impairment in patients with epilepsy. Compared with a control
      epilepsy group, in the topiramate-treated group, there was significantly less
      activation in the language-mediating regions of the prefrontal cortex; the
      topiramate group also had significantly lower neuropsychological language scores.
      These findings suggest that topiramate has a critical effect on the cerebral
      neural systems that mediate expressive language.

PMID- 16793347
TI  - Diagnostic performance of primary 3-dimensional computed tomography colonography
      in the setting of colonic diverticular disease.
AB  - BACKGROUND & AIMS: Colonic diverticular disease (CDD) is a leading cause of
      nondiagnostic segmental evaluation at computed tomography colonography (CTC). The
      primary goal of this study was to evaluate the impact of CDD on polyp detection
      at primary 3-dimensional (3D) CTC. METHODS: The study group consisted of 280
      asymptomatic average-risk adults (mean age, 58.1 y; 167 men, 113 women). All
      patients underwent CTC followed by same-day optical colonoscopy with segmental
      unblinding (reference standard). Primary 3D endoluminal evaluation with 2
      dimensional correlation was used for initial polyp detection at CTC. Without
      knowledge of polyp findings, all colonic segments were reviewed for the presence
      of CDD and graded as absent, minimal, moderate, or extensive disease. RESULTS:
      Moderate or extensive CDD was present in 271 (12.1%) of 2240 colonic segments and
      142 (50.7%) of 280 patients. CTC performance for polyps 6 mm or larger in the
      presence and absence of moderate-extensive CDD was as follows: by-segment
      sensitivity of 90.3% (28/31) and 79.4% (123/155); by-patient sensitivity of 86.5%
      (64/74) and 83.1% (54/65); by-segment specificity of 97.1% (233/240) and 97.7%
      (1772/1814); by-patient specificity of 83.8% (57/68) and 83.6% (61/73); by
      segment positive predictive value of 80.0% (28/35) and 74.5% (123/165); by
      patient positive predictive value of 85.3% (64/75) and 81.8% (64/66); by-segment
      negative predictive value of 98.7% (233/236) and 98.2% (1172/1804); and by
      patient negative predictive value of 85.1% (57/67) and 84.7% (61/72),
      respectively (not significant, P > or = .15). CONCLUSIONS: CDD was common in this
      asymptomatic screening population, but its presence did not degrade the
      diagnostic performance of primary 3D CTC for polyp detection.

PMID- 16793348
TI  - A simple method to fabricate a chitosan-gold nanoparticles film and its
      application in glucose biosensor.
AB  - A novel film of chitosan-gold nanoparticles is fabricated by a direct and facile
      electrochemical deposition method and its application in glucose biosensor is
      investigated. HAuCl(4) solution is mixed with chitosan and electrochemically
      reduced to gold nanoparticles, which can be stabilized by chitosan and
      electrodeposited onto glassy carbon electrode surfaces along with the
      electrodeposition of chitosan. Then a model enzyme, glucose oxidase (GOD) is
      immobilized onto the resulting film to construct a glucose biosensor through self
      assembly. The resulting modified electrode surfaces are characterized with both
      AFM and cyclic voltammetry. Effects of chitosan and HAuCl(4) concentration in the
      mixture together with the deposition time and the applied voltage on the
      amperometric response of the biosensor are also investigated. The linear range of
      the glucose biosensor is from 5.0 x 10(-5) approximately 1.30 x 10(-3) M with a
      Michaelis-Menten constant of 3.5 mM and a detection limit of about 13 microM.

PMID- 16793349
TI  - Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch
      recombination in chromosomal translocations.
AB  - When a single double-strand break arises in the genome, nonhomologous DNA end
      joining (NHEJ) is a major pathway for its repair. When double-strand breaks arise
      at two nonhomologous sites in the genome, NHEJ also appears to be a major pathway
      by which the translocated ends are joined. The mechanism of NHEJ is briefly
      summarized, and alternative enzymes are also discussed. V(D)J recombination and
      class switch recombination are specialized processes designed to create double
      strand DNA breaks at specific locations in the genomes of lymphoid cells.
      Sporadic Burkitt's lymphoma and myelomas can arise due to translocation of the c
      myc gene into the Ig heavy chain locus during class switch recombination. In
      other lymphoid neoplasms, the RAG complex can create double-strand breaks that
      result in a translocation. Such RAG-generated breaks occur at very specific
      nucleotides that are directly adjacent to sequences that resemble canonical
      heptamer/nonamer sequences characteristic of normal V(D)J recombination. This
      occurs in some T cell leukemias and lymphomas. The RAG complex also appears
      capable of recognizing regions for their altered DNA structure rather than their
      primary sequence, and this may account for the action by RAGs at some chromosomal
      translocation sites, such as at the bcl-2 major breakpoint region in the
      follicular lymphomas that arise in B lymphocytes.

PMID- 16793350
TI  - Achromobacter xylosoxidans in cystic fibrosis: prevalence and clinical relevance.
AB  - BACKGROUND: Achromobacter xylosoxidans is increasingly cultured in sputum from
      cystic fibrosis (CF) patients; nevertheless, there are few published data on the
      clinical impact of this infection or chronic colonisation. METHODS: Relying on
      DNA fingerprinting techniques we studied the prevalence of A. xylosoxidans in our
      CF population. In a retrospective case control study the clinical status of
      patients with at least 3 sputum cultures positive for A. xylosoxidans over at
      least 9 months, at the moment of the first positive culture and during the period
      of colonisation were compared to age (+/-1 year), gender and to Pseudomonas
      aeruginosa colonisation controlled CF patients who had never A. xylosoxidans
      positive sputum cultures. RESULTS: The prevalence of patients with at least one
      positive A. xylosoxidans culture was 17.9%. 5.3% of the patients fulfilled the
      criteria of our definition of colonisation. Colonised patients had a median age
      of 20 years (range 11-27 years) and a mean colonisation period of 1.5 (+/-0.9)
      years. At the moment of the first positive culture we found significantly lower
      Bhalla scores on HRCT scans of the lungs (11+/-3 versus 16+/-3, p<0.002), lower
      Brasfield chest X-ray scores (14+/-3 versus 18+/-3, p<0.019), lower FVC values
      (70%+/-22 versus 94%+/-12, p<0.017) and lower FEV(1) values (55%+/-32 versus
      78%+/-23, p=0.123), although the latter did not reach significance. There was no
      significant difference in body mass index (BMI) (18.7+/-3 kg/m2 versus 19.6+/-3
      kg/m2, p=0.8). Over the study period A. xylosoxidans-colonised patients did have
      more need for intravenous antibiotic treatment courses (19 versus 5, p<0.001);
      nevertheless, there was no significant difference in lung function decline over
      the study period (FVC: -6.25+/-12.34% versus -5.62+/-8.30%, p 0.77, FEV1: -5.62+/
      8.30% versus -1.87+/-11.58%, p<0.47). CONCLUSIONS: The prevalence of A.
      xylosoxidans infection or colonisation is probably underestimated. Colonised
      patients are mostly older, with more pronounced lung damage and lower lung
      function values. Although there was more need for intravenous antibiotic
      treatment courses, no faster decline in lung function was observed in A.
      xylosoxidans positive patients.

PMID- 16793351
TI  - Determination of quinolones residues in prawn using high-performance liquid
      chromatography with Ce(IV)-Ru(bpy)(3)2+-HNO3 chemiluminescence detection.
AB  - A novel method was developed for the determination of quinolone (QN) residues
      such as ofloxacin, norfloxacin, ciprofloxacin and lomefloxacin by high
      performance liquid chromatography (HPLC) coupled with chemiluminescence (CL)
      detection. The procedure was based on the chemiluminescent enhancement by QNs of
      the Ce(SO(4))(2)-Ru(bpy)(3)(2+)-HNO(3) system. The separation was carried out
      with an isocratic elution using the mobile phase of 3:15:82 (v/v/v) acetonitrile
      methanol-ammonium acetate buffer (containing 7.5 x 10(-4)M TBAB, 0.8% (v/v) TEA
      and 1.0 x 10(-4)M ammonium acetate, pH 3.65) at a flow rate of 1.0 ml/min. For
      the four QNs, the detection limits at a signal-to-noise of 3 ranged from 0.36 to
      2.4 ng/ml. The relative standard deviations for the determination of QNs ranged
      from 1.6 to 4.5% within a day (n=11) and from 3.7 to 6.2% in three days (n=15),
      respectively. The method was successfully applied to the determination of QNs in
      prawn samples. The possible mechanism of the CL reaction was also discussed
      briefly.

PMID- 16793352
TI  - High performance liquid chromatography analysis of 2-mercaptoethylamine
      (cysteamine) in biological samples by derivatization with N-(1-pyrenyl) maleimide
      (NPM) using fluorescence detection.
AB  - 2-Mercaptoethylamine (cysteamine) is an aminothiol compound used as a drug for
      the treatment of cystinosis, an autosomal recessive lysosomal storage disorder.
      Because of cysteamine's important role in clinical settings, its analysis by
      sensitive techniques has become pivotal. Unfortunately, the available methods are
      either complex or labor intensive. Therefore, we have developed a new rapid,
      sensitive, and simple method for determining cysteamine in biological samples
      (brain, kidney, liver, and plasma), using N-(1-pyrenyl) maleimide (NPM) as the
      derivatizing agent and reversed-phase high performance liquid chromatography
      (HPLC) with a fluorescence detection method (lambda(ex)=330 nm, lambda(em)=376
      nm). The mobile phase was acetonitrile and water (70:30) with acetic acid and o
      phosphoric acid (1 mL/L). The calibration curve for cysteamine in serine borate
      buffer (SBB) was found to be linear over a range of 0-1200 nM (r(2)=0.9993), and
      in plasma and liver matrix, the r(2) values were 0.9968 and 0.9965, respectively.
      The coefficients of the variation for the within-run and between-run precisions
      ranged from 0.68 to 9.90% and 0.63 to 4.17%, respectively. The percentage of
      relative recovery ranged from 94.1 to 98.6%.

PMID- 16793354
TI  - Pulmonary alterations in patients with chronic HCV infection.
AB  - BACKGROUND: Chronic hepatitis C virus infection has been reported in association
      with several extrahepatic manifestations. Included in this list is interstitial
      lung involvement. AIMS: The aim of the present study was to evaluate pulmonary
      alterations in patients with chronic hepatitis C virus infection. PATIENTS:
      Twenty-one patients with chronic hepatitis C virus infection were enrolled into a
      prospective study. One patient has been excluded because of underlying
      tuberculosis. METHODS: All patients underwent pulmonary function tests, diffusion
      capacity for carbon monoxide and high-resolution computed tomography of the
      chest. RESULTS: Forced vital capacity, forced expiratory volume in first
      second/forced vital capacity and forced expiratory volume in first second values
      were reduced to less than 80% of predicted values in 3, 11 and 5 patients,
      respectively. Diffusion capacity for carbon monoxide was low in 12 patients
      (60%), 8 of whom had simultaneous decrease in diffusion capacity for carbon
      monoxide/VA values. Thorax high-resolution computed tomography revealed abnormal
      findings in eight patients (40%). Fifteen patients with chronic hepatitis C virus
      infection (75%) had at least one pulmonary alteration as evidenced by abnormal
      pulmonary function tests, diffusion capacity for carbon monoxide and/or high
      resolution computed tomography results. CONCLUSION: In spite of a limited study
      population, these findings may implicate that pulmonary manifestations of chronic
      hepatitis C virus infection are frequently underdiagnosed.

PMID- 16793353
TI  - Aspartic acid 214 in Citrobacter freundii tyrosine phenol-lyase ensures
      sufficient C--H-acidity of the external aldimine intermediate and proper
      orientation of the cofactor at the active site.
AB  - In the X-ray structure of tyrosine phenol-lyase (TPL) Asp214 is located at H
      bonding distance from the N1 atom of the cofactor. This residue has been replaced
      with Ala and Asn and the properties of the mutant enzymes have been studied. The
      substitutions result in a decrease in the cofactor affinity of about four orders
      of magnitude. D214A and D214N TPLs do not catalyze the decomposition of l-Tyr and
      3-fluoro-l-Tyr. They decompose substrates, containing better leaving groups with
      rates reduced by one or two orders of magnitude. Lognormal resolution of the
      spectra of the mutant enzymes revealed that the N1 atom of the cofactor is
      deprotonated. Spectral characteristics of internal and external aldimines of the
      mutant TPLs and the data on their interaction with quasisubstrates demonstrate
      that replacements of Asp214 lead to alteration of active site conformations. The
      mutant enzymes do not form noticeable amounts of a quinonoid upon interaction
      with inhibitors, but catalyze isotope exchange of C-alpha-proton of a number of
      amino acids for deuterium in (2)H(2)O. The k(ex) values for the isotope exchange
      of l-phenylalanine and 3-fluoro-l-tyrosine are close to the k(cat) values for
      reacting substrates. Thus, for the mutant TPLs the stage of C-alpha-proton
      abstraction may be considered as a rate-limiting for the whole reaction.

PMID- 16793355
TI  - Stresses in growing soft tissues.
AB  - Biochemical processes of tissue growth lead to production of new proteins, cells,
      and other material particles at the microscopic level. At the macroscopic level,
      growth is marked by the change of the tissue shape and mass. In addition, the
      appearance of the new material particles is generally accompanied by deformation
      and, consequently, stresses in the surrounding material. Built upon a microscopic
      toy-tissue model mimicking the mechanical processes of mass supply, a simple
      phenomenological theory of tissue growth is used in the present work for
      explaining residual stresses in arteries and studying stresses around growing
      solid tumors/multicell spheroids. It is shown, in particular, that the uniform
      volumetric growth can lead to accumulation of residual stresses in arteries
      because of the material anisotropy. This can be a complementary source of
      residual stresses in arteries as compared to the stresses induced by non-uniform
      tissue growth. It is argued that the quantitative assessment of the residual
      stresses based on in vitro experiments may not be reliable because of the
      essential stress redistribution in the tissue samples under the cutting process.
      Concerning the problem of tumor growth, it is shown that the multicell spheroid
      or tumor evolution depends on elastic properties of surrounding tissues. In good
      qualitative agreement with the experimental in vitro observations on growing
      multicell spheroids, numerical simulations confirm that stiff hosting tissues can
      inhibit tumor growth.

PMID- 16793356
TI  - Minute changes in composition of polymer substrates produce amplified differences
      in cell adhesion and motility via optimal ligand conditioning.
AB  - We explored the interplay between substratum chemistry of polymeric materials and
      surface-adsorbed ligand concentration (human plasma fibronectin) in the control
      of cell adhesion and cell motility. We found that small changes in the chemical
      composition of a polymeric substratum had different effects on cellular motility-
      depending on the concentration of preadsorbed fibronectin. We used two tyrosine
      derived polyarylates, poly(DTD diglycolate) and poly(DTD glutarate), as substrata
      for the seeding of NIH-3T3 fibroblasts. The only compositional difference between
      the two test polymers was that one single oxygen atom in the polymer backbone of
      poly(DTD diglycolate) had been substituted by a methylene group in the backbone
      of poly(DTD glutarate), The two polymers had closely matched hydrophobicity and
      physical properties. Flat, spin-coated surfaces of these polymers were pretreated
      with different concentrations of human plasma fibronectin (0-20 microg/ml). After
      seeding with NIH-3T3 fibroblasts, we examined the adhesion and motility behavior
      of these cells. We found that NIH-3T3 fibroblasts migrated significantly faster
      on poly(DTD diglycolate), but only when the polymer surfaces were pretreated with
      intermediate concentrations of fibronectin. Only at these intermediate levels of
      ligand conditioning, did the presence of an extra oxygen atom in the backbone of
      poly(DTD diglycolate) relative to poly(DTD glutarate) (i) alter the overall
      organization/concentration of the fibronectin; (ii) weaken cell attachment
      strength and inhibited excessive cell spreading; and (iii) promote cell motility
      kinetics. These findings indicate that the biological effect of minute changes in
      substratum chemistry is critically dependent on the level of surface-adsorbed
      cell-binding ligands.

PMID- 16793357
TI  - Lipopolysaccharide-induced inflammation and perinatal brain injury.
AB  - Both energy failure and infections are important risk factors for brain injury in
      term and preterm infants. In this review we focus on recent experimental studies
      that have examined the effects of lipopolysaccharide (LPS) exposure to the fetus
      or neonate and the interaction of LPS with other events. Intracerebral LPS
      injections induce a marked cerebral cytokine response and prominent white matter
      lesions. LPS administered intravenously to the fetus also induces gross lesions,
      which are mainly localised to the white matter and are accompanied by activation
      of inflammatory cells. Cerebral effects following fetal LPS exposure via more
      distant routes, such as intracervical, intrauterine or maternal LPS
      administration, are characterised by reductions in oligodendrocyte or myelin
      markers without macroscopic lesions being evident. Both antenatal and neonatal
      LPS exposures increase the sensitivity of the brain to subsequent
      hypoxic/ischaemic events, even in adulthood. These studies suggest that fetal
      inflammation is the strongest predictor of brain lesions.

PMID- 16793358
TI  - Low-amplitude, broad-frequency vibration effects on cortical bone formation in
      mice.
AB  - Mechanical loading of the skeleton is necessary to maintain bone structure and
      strength. Large amplitude strains associated with vigorous activity typically
      result in the greatest osteogenic response; however, data suggest that low
      amplitude, broad-frequency vibration results in new bone formation and may
      enhance adaptation through a stochastic resonance (SR) phenomenon. That is,
      random noise may maximally enhance bone formation to a known osteogenic stimulus.
      The aims of this study were to (1) assess the ability of different vibration
      signals to enhance cortical bone formation during short- and long-term loading
      and (2) determine whether vibration could effect SR in bone. Two studies were
      completed wherein several osteogenic loading waveforms, with or without an
      additive low-amplitude, broad-frequency (0-50 Hz) vibration signal, were applied
      to the mouse ulna in axial compression. In study 1, mice were loaded short-term
      (30 s/day, 2 days) with either a carrier signal alone (1 or 2 N sine waveform),
      vibration signal alone [0.1 N or 0.3 N root mean square (RMS)] or combined
      carrier and vibration signal. In study 2, mice were loaded long-term (30 s/day, 3
      days/week, 4 weeks) with a carrier signal alone (static or sine waveform),
      vibration signal alone (0.02 N, 0.04 N, 0.08 N or 0.25 N RMS) or combined carrier
      and vibration signal. Sequential calcein bone labels were administered at 2 and 4
      days and at 4 and 29 days after the first day of loading in study 1 and 2,
      respectively; bone formation parameters and changes in geometry were measured.
      Combined application of the carrier and vibration signals in study 1 resulted in
      significantly greater bone formation than with either signal alone (P < 0.001);
      however, this increase was independently explained by increased strain levels
      associated with additive vibration. When load and strain levels were similar
      across loading groups in study 2, cortical bone formation and changes in geometry
      were not significantly altered by vibration. Vibration alone did not result in
      any new bone formation. Our data suggest that low-amplitude, broad-frequency
      vibration superimposed onto an osteogenic waveform or vibration alone does not
      enhance cortical bone adaptation at the frequencies, amplitudes and loading
      periods tested.

PMID- 16793359
TI  - Assays for determining lesion bypass efficiency and mutagenicity of site-specific
      DNA lesions in vivo.
AB  - DNA damage, if left unrepaired, may hinder translesion synthesis, leading to
      cytotoxicity, and instruct a DNA polymerase to incorporate an incorrect incipient
      base opposite the damage, leading to mutagenicity. This chapter describes
      technology used to measure quantitatively the degree to which a specific type of
      DNA damage impedes DNA replication. The technology also quantifies the mutation
      frequency and specificity of such damage after replication within cells. If cells
      with defined defects in DNA repair are used as hosts for replication, one can
      pinpoint the specific enzymes or pathways of repair that are operative on
      specific types of DNA damage.

PMID- 16793360
TI  - Oxidative DNA glycosylases: recipes from cloning to characterization.
AB  - As new organisms are being sequenced on a daily basis, new DNA glycosylases that
      recognize DNA damage can be easily identified in an effort to understand both
      their phylogenetics and substrate specificities. As a practical matter, existing
      bacterial and human homologs need to be readily available as laboratory reagents
      in order to compare the activities of the novel enzymes to existing enzymes. This
      chapter attempts to provide a primer for cloning, expression, and assay
      procedures for bacterial and human DNA glycosylases that recognize oxidative DNA
      damages. These methodologies can be translated readily to novel DNA glycosylases
      or to DNA glycosylases that recognize other types of DNA damages.

PMID- 16793361
TI  - Purification and characterization of NEIL1 and NEIL2, members of a distinct
      family of mammalian DNA glycosylases for repair of oxidized bases.
AB  - NEIL1 and NEIL2 were newly discovered as mammalian orthologs of Escherichia coli
      Nei and Fpg, oxidized base-specific DNA glycosylases. These are distinct from
      previously characterized OGG1 and NTH1, the other two glycosylases for repairing
      oxidatively damaged bases in mammalian cells, in regards to reaction mechanism.
      Recombinant human NEIL1 and NEIL2 were purified from E. coli and biochemically
      characterized. Some damaged bases are common substrates for both groups of
      enzymes. However, in contrast to the lack of activity of NTH1 and OGG1 for
      substrate lesions in single-stranded DNA, the NEILs have unique preference for
      bubble or single-stranded DNA substrates, suggesting their preferential
      involvement in repairing transcribed or replicating DNA sequences.

PMID- 16793362
TI  - Analysis of base excision DNA repair of the oxidative lesion 2-deoxyribonolactone
      and the formation of DNA-protein cross-links.
AB  - DNA base lesions arising from oxidation or alkylation are processed primarily by
      the base excision repair pathway (BER). The damaged bases are excised by DNA N
      glycosylases, which generate apurinic/apyrimidinic (AP) sites; AP sites produced
      by hydrolytic decay of DNA or the spontaneous loss of damaged bases are also
      processed by BER. Free radicals produce various types of abasic lesions as
      oxidative damage. This chapter focuses on the analysis of DNA repair and other
      reactions that occur with the lesion 2-deoxyribonolactone (dL), which has
      received much attention recently. DNA substrates with site-specific dL lesions
      are generated by photolysis of a synthetic precursor residue; both small
      oligonucleotide and plasmid-based substrates can be produced. The dL residue is
      readily incised by AP endonucleases such as the mammalian Ape1 protein, which
      would bring the lesion into BER. However, the second enzyme of the canonical BER
      pathway, DNA polymerase beta, instead of excising Ape1-incised dL, forms a stable
      DNA-protein cross-link with the lesion. Such cross-links are analyzed by
      polyacrylamide gel electrophoresis. Incubation of Ape1-incised dL substrates with
      mammalian cell-free extracts shows that other proteins can also form such cross
      links, although DNA polymerase beta appears to be the major species. This chapter
      presents methods for analyzing the extent of DNA repair synthesis (repair patch
      size) associated with dL in whole cell extracts. These analyses show that dL is
      processed nearly exclusively by the long patch BER pathway, which results in the
      repair synthesis of two or more nucleotides.

PMID- 16793363
TI  - Isolation and analyses of MutY homologs (MYH).
AB  - The base excision repair carried out by the bacterial MutY DNA glycosylase and
      eukaryotic MutY homolog (MYH) is responsible for removing adenines
      misincorporated into DNA opposite 7,8-dihydro-8-oxo-guanines (8-oxoG), thereby
      preventing G:C to T:A mutations. MutY and MYH can also remove adenines from A/G
      and A/C and can remove guanines from G/8-oxoG mismatches at reduced rates.
      Biallelic germline mutations in the human MYH gene predispose individuals to
      multiple colorectal adenomas and carcinoma. Four functional assays are usually
      employed to characterize the MutY and MYH. Gel mobility shift or fluorescence
      anisotropy assays measures DNA-binding affinity and the apparent dissociation
      constants. Glycosylase assay determines the catalytic parameters of the enzyme.
      By using a trapping assay in the presence of sodium borohydride, the protein-DNA
      covalent intermediate can be identified. The in vivo activity of MutY or MYH can
      be measured by complementation in Escherichia coli mutY mutants or fission yeast
      Schizosaccharomyces pombe MYH knockout cells. MutY and MYH interacting proteins
      can be analyzed by the glutathione S-transferase pull-down assay, Far-western,
      and coimmunoprecipitation. The in vitro and in vivo activities of MYH can be
      modulated by several proteins, including mismatch recognition enzymes MSH2/MSH6,
      proliferating cell nuclear antigen, and apurinic/apyrimidinic endonuclease.

PMID- 16793364
TI  - Use of yeast for detection of endogenous abasic lesions, their source, and their
      repair.
AB  - Apurinic/apyrimidinic (AP) sites are expected to be one of the most frequent
      endogenous lesions in DNA. AP sites are potentially lethal and mutagenic. Data
      shows that the simultaneous inactivation of two AP endonucleases (Apn1 and Apn2)
      and of the nuclease Rad1-Rad10 causes cell death in Saccharomyces cerevisiae. We
      suggest that the essential function of Apn1, Apn2, and Rad1-Rad10 is to repair
      endogenous AP sites and related 3'-blocked single strand breaks. This data led us
      to conclude that the burden of endogenous AP sites is not compatible with life in
      absence of DNA repair. This chapter describes two genetic assays to investigate
      origin, repair, and biological consequences of endogenous AP sites in yeast. The
      first assay relies on genetic crosses and tetrad analysis and uses the apn1 apn2
      rad1 triple mutant. The apn1 apn2 rad1 triple mutant is unviable; however, it can
      form microcolonies. By means of genetic crosses, apn1 apn2 rad1 x quadruple
      mutants are generated. The size of the colonies formed by each quadruple mutant
      is compared to that of the apn1 apn2 rad1 triple mutant. Three classes of genes
      (x) were identified: (i) genes whose inactivation aggravates the phenotype
      (reduces microcolony size), such as RAD9, RAD50, RAD51, RAD52, MUS81, and MRE11;
      (ii) genes whose inactivation alleviates the phenotype, such as UNG1, NTG1, and
      NTG2; and (iii) genes whose inactivation is neutral, such as MAG1 or OGG1. The
      second assay uses the apn1 apn2 rad14 triple mutant, which is viable but exhibits
      a spontaneous mutator phenotype. This mutant was used in a colethal screen. This
      assay allowed the identification of mutation in DNA repair genes such as RAD1 or
      RAD50, as well as a mutation in the DUT1 gene coding for the dUTPase, which has
      impact on the formation of AP sites in DNA. A model that summarizes our present
      and puzzling data on the origin and repair of endogenous AP sites is also
      presented.

PMID- 16793365
TI  - Activities and mechanism of DNA polymerase beta.
AB  - DNA polymerase beta plays an essential role in the base excision repair pathway
      necessary to cleanse the genome of simple base lesions and abasic sites. Abasic
      sites arise in DNA from spontaneous base loss (depurination) and DNA-damage
      specific glycosylases that hydrolyze the N-glycosidic bond between the
      deoxyribose and the damaged base. DNA polymerase beta contributes two enzymatic
      activities: DNA synthesis and deoxyribose-phosphate removal through nucleotidyl
      transferase and lyase mechanisms, respectively. The active site for each of these
      activities resides on a distinct domain of the protein: 31-kDa polymerase domain
      and amino-terminal 8-kDa lyase domain. The simple organization of each domain and
      the ability to assay each activity have hastened our understanding of the
      faithful replication of DNA during repair synthesis and the flux of intermediates
      through single nucleotide base excision repair and its alternate pathways.

PMID- 16793366
TI  - Direct removal of alkylation damage from DNA by AlkB and related DNA
      dioxygenases.
AB  - The cytotoxic alkylation lesions 1-methyladenine (1-alkyladenine) and 3
      methylcytosine are removed efficiently from DNA by direct damage reversal,
      catalyzed by the Escherichia coli AlkB protein and its human homologs ABH2 and
      ABH3. The enzymes act by oxidative demethylation, employing Fe(II) and alpha
      ketoglutarate as cofactors, and release the methyl moiety as formaldehyde. The
      isolation of these enzymes from overproducing cells is described, as well as the
      preparation of radioactively labeled substrates and procedures for enzyme assays.
      Functionality in vivo is examined by complementation of the low survival of
      alkylated single-stranded DNA bacteriophage in an E. coli alkB mutant.

PMID- 16793367
TI  - Purification and characterization of DNA photolyases.
AB  - Members of the photolyase/cryptochrome family of blue-light photoreceptors are
      monomeric proteins of 50-70 kDa that contain two noncovalently bound
      chromophores/cofactors: either folate or deazaflavin, which act as a
      photoantenna, and a two electron-reduced FAD, which acts as a catalytic cofactor.
      DNA photolyases bind their substrates with high affinity and specificity and
      subsequently use blue light as a cosubstrate for the in situ conversion of
      ultraviolet-induced cyclobutane pyrimidine dimers and (6-4) photoproducts to
      canonical bases, thereby restoring the integrity of DNA. The determinants for
      binding, as well as the mechanism of the photolysis reaction, have been studied
      extensively using highly purified enzyme. In contrast, neither the substrate nor
      the reaction catalyzed by the closely related cryptochromes has been identified.
      This chapter describes methods used to purify DNA photolyases from a variety of
      organisms using an Escherichia coli overexpression system, as well as the
      properties of the purified enzymes and some of the assays commonly used to study
      DNA binding and repair by these enzymes in vitro.

PMID- 16793368
TI  - Genetic and in vitro assays of DNA deamination.
AB  - The DNA deaminase family encompasses enzymes that have been highly conserved
      throughout vertebrate evolution and which display wide-ranging positive effects
      upon innate and adaptive immune system and development. Activation-induced
      cytidine deaminase was identified as a DNA mutator after its necessity in the
      successful development of high-affinity B cells via somatic hypermutation, class
      switch recombination, and gene conversion was determined. APOBEC3 exhibits the
      ability to deaminate retroviral first strand cDNA in a variety of viral
      infections, including HIV and hepatitis. Recent work has highlighted the
      potential importance of activation-induced cytidine deaminase (AID) and APOBEC1
      in epigenetic reprogramming, and also the role that AID and the APOBECs may have
      in the development of cancer. In addition to the known activities of these
      members of the protein family, there are still other deaminases, such as APOBEC2,
      whose targets and functions are as yet unknown. This chapter provides the details
      of two assays that have proved to be invaluable in elucidating the exact
      specificities of deaminases both in vitro and in Escherichia coli. The
      application of these assays to future studies of the deaminase family will
      provide an indispensible tool in determining the potentially diverse functions of
      the remainder of this family of enzymes.

PMID- 16793369
TI  - The xeroderma pigmentosum group C protein complex and ultraviolet-damaged DNA
      binding protein: functional assays for damage recognition factors involved in
      global genome repair.
AB  - In mammalian nucleotide excision repair (NER) operating throughout the genome,
      DNA lesions are recognized by protein factors that specifically bind to the
      damaged sites. Such damage recognition factors involve the xeroderma pigmentosum
      group C (XPC) protein complex and ultraviolet (UV)-damaged DNA-binding protein
      (UV-DDB). To assess specific DNA-binding activities of these factors, it is
      useful to take advantage of biochemical assays using DNA substrates that contain
      a defined lesion and/or artificial structure in a site-specific manner. In
      addition, it has been shown that both XPC and UV-DDB are ubiquitylated in
      response to UV irradiation of cells. This ubiquitylation is mediated by ubiquitin
      ligase associated with UV-DDB and is important for the NER process of UV-induced
      lesions. Methods for detecting the UV-DDB-dependent ubiquitylation in vivo and in
      vitro are also described.

PMID- 16793370
TI  - Purification and characterization of Escherichia coli and human nucleotide
      excision repair enzyme systems.
AB  - Nucleotide excision repair is a multicomponent, multistep enzymatic system that
      removes a wide spectrum of DNA damage by dual incisions in the damaged strand on
      both sides of the lesion. The basic steps are damage recognition, dual incisions,
      resynthesis to replace the excised DNA, and ligation. Each step has been studied
      in vitro using cell extracts or highly purified repair factors and radiolabeled
      DNA of known sequence with DNA damage at a defined site. This chapter describes
      procedures for preparation of DNA substrates designed for analysis of damage
      recognition, either the 5' or the 3' incision event, excision (resulting from
      concerted dual incisions), and repair synthesis. Excision in Escherichia coli is
      accomplished by the three-subunit Uvr(A)BC excision nuclease and in humans by six
      repair factors: XPA, RPA, XPChR23B, TFIIH, XPFERCC1, and XPG. This chapter
      outlines methods for expression and purification of these essential repair
      factors and provides protocols for performing each of the in vitro repair assays
      with either the E. coli or the human excision nuclease.

PMID- 16793371
TI  - Assays for transcription elongation by RNA polymerase II using oligo(dC)-tailed
      template with single DNA damage.
AB  - A DNA molecule is vulnerable to many types of DNA-damaging agents of endogenous
      and environmental origins. Although damage to DNA can interfere not only with
      replication but also transcription, the majority of DNA repair and mutagenesis
      studies are based on the actions of DNA polymerases in DNA replication. To
      investigate the actions of RNA polymerase II (RNAPII) encountering a single DNA
      lesion on transcription elongation, we employ a transcription elongation assay
      using purified RNAPII and oligo(dC)-tailed templates containing a DNA lesion at a
      specific site. This chapter describes an analysis of whether elongating RNAPII
      stalls at a DNA lesion or whether RNAPII generates mutations in RNA transcripts.

PMID- 16793372
TI  - In vivo assays for transcription-coupled repair.
AB  - This chapter describes the technologies used in our respective laboratories to
      study the incidence and repair of lesions induced in specific DNA sequences by
      ultraviolet light, chemical carcinogens, and products of cellular metabolism. The
      Southern blot method is suitable for analysis of damage and repair in the
      individual DNA strands of specific restriction fragments up to 25,000 nucleotides
      in length, whereas the ligation-mediated polymerase chain reaction approach
      permits analysis of shorter sequences at the nucleotide level. Both methods have
      unique advantages and limitations for particular applications.

PMID- 16793373
TI  - TFIIH enzymatic activities in transcription and nucleotide excision repair.
AB  - Transcription and nucleotide excision repair (NER) are two major mechanisms in
      which the transcription factor TFIIH plays a crucial role. In order to
      investigate its function, we first described a fast and efficient purification
      protocol of TFIIH from either HeLa cells or patient cell lines, as well as
      various in vitro enzymatic assays set up in our laboratory. All these enzymatic
      assays have been adapted to work on immobilized DNA, a powerful tool allowing for
      sequential protein incubations in various buffer conditions, without
      destabilizing protein complexes bound to the DNA. Runoff transcription assays
      performed with either whole cell extract or highly purified factors underline the
      role of TFIIH helicases (XPB and XPD) in the RNA synthesis. Moreover, the
      requirement of XPB and XPD in NER can also be investigated with various assays
      corresponding to the different steps of this process. The DNA opening assay
      (permanganate footprint) highlights DNA unwinding of the double-stranded DNA
      fragment within the repair complex, whereas the dual incision assay allows for
      detection of the double cut on both sides of the lesion. The gap-filling reaction
      following the cuts can be monitored as well with a DNA resynthesis assay.
      Futhermore, the use of immobilized DNA is of great interest to study the detailed
      mechanism in which TFIIH plays a central role. This chapter describes the ATP
      independent recruitment of TFIIH on the damaged DNA previously recognized by XPC
      hHR23B and the sequential arrival and departure of the repair proteins within the
      NER complex.

PMID- 16793374
TI  - An assay for studying ubiquitylation of RNA polymerase II and other proteins in
      crude yeast extracts.
AB  - In recent years, much research effort has been invested in understanding the role
      and importance of protein ubiquitylation. This chapter presents protocols that
      enable ubiquitylation of RNAPII and other proteins to be reconstituted in crude
      yeast extracts in vitro. These procedures, combined with the ease of genetic
      manipulations in yeast, provide a new powerful tool for investigating the
      mechanisms underlying protein ubiquitylation.

PMID- 16793375
TI  - Analysis of the excision step in human DNA mismatch repair.
AB  - The reaction responsible for replication error correction by mismatch repair
      proceeds via several steps: mismatch recognition, mismatch-provoked excision,
      repair DNA synthesis, and ligation. Key steps in this process are the recognition
      and subsequent exonucleolytic removal of the mispair. A minimal system comprised
      of human MutSalpha (MSH2*MSH6), MutLalpha (MLH1*PMS2), exonuclease I (EXOI),
      replication protein A (RPA), proliferating cell nuclear antigen (PCNA), and
      replication factor C (RFC) is sufficient to support mismatch-provoked excision in
      vitro. This chapter describes methods for analysis of the reconstituted excision
      reaction.

PMID- 16793376
TI  - Characterization of the "mismatch repairosome" and its role in the processing of
      modified nucleosides in vitro.
AB  - The process of postreplicative mismatch repair (MMR) increases the fidelity of
      DNA replication by eliminating biosynthetic errors from newly synthesized DNA. In
      addition, MMR proteins are also involved in the processing of intermediates of
      mitotic and meiotic recombination and, in mammalian cells, play a role in DNA
      damage signaling. As mismatches cannot be induced in the DNA of living cells, the
      study of the molecular transactions during MMR is restricted to in vitro systems.
      This chapter describes the construction of heteroduplex substrates that can be
      used for DNA affinity purification of MMR protein complexes and for the study of
      the role of eukaryotic MMR proteins in the processing of modified nucleosides.

PMID- 16793377
TI  - Analysis of DNA mismatch repair in cellular response to DNA damage.
AB  - Significant advances have been made in identifying and characterizing the roles
      of DNA mismatch repair (MMR) proteins in cellular response to DNA damage.
      Insights into this process have been obtained by performing interactions of
      mismatch recognition proteins (e.g., MutSalpha) with DNA adduct-containing
      duplexes and by analyzing cellular responses (including cell cycle checkpoints
      and apoptosis) of cell lines and animals with various MMR capacities. This
      chapter presents detailed methods for gel-shift analysis to determine the
      interaction between MutSalpha and oligonucleotide duplex containing a single DNA
      adduct and for apoptotic assays in cell lines and experimental animals. In
      addition, a step-by-step protocol is also provided for the purification of
      MutSalpha from human cells, the preparation of DNA substrates containing a
      defined DNA adduct, and the treatment of MMR-proficient and deficient cell lines
      as well as MMR knockout mice.

PMID- 16793378
TI  - Characterization of Escherichia coli translesion synthesis polymerases and their
      accessory factors.
AB  - Members of the Y family of DNA polymerases are specialized to replicate lesion
      containing DNA. However, they lack 3'-5' exonuclease activity and have reduced
      fidelity compared to replicative polymerases when copying undamaged templates,
      and thus are potentially mutagenic. Y family polymerases must be tightly
      regulated to prevent aberrant mutations on undamaged DNA while permitting
      replication only under conditions of DNA damage. These polymerases provide a
      mechanism of DNA damage tolerance, confer cellular resistance to a variety of DNA
      damaging agents, and have been implicated in bacterial persistence. The Y family
      polymerases are represented in all domains of life. Escherichia coli possesses
      two members of the Y family, DNA pol IV (DinB) and DNA pol V (UmuD'(2)C), and
      several regulatory factors, including those encoded by the umuD gene that
      influence the activity of UmuC. This chapter outlines procedures for in vivo and
      in vitro analysis of these proteins. Study of the E. coli Y family polymerases
      and their accessory factors is important for understanding the broad principles
      of DNA damage tolerance and mechanisms of mutagenesis throughout evolution.
      Furthermore, study of these enzymes and their role in stress-induced mutagenesis
      may also give insight into a variety of phenomena, including the growing problem
      of bacterial antibiotic resistance.

PMID- 16793379
TI  - Measuring the fidelity of translesion DNA synthesis.
AB  - A method is described to measure the fidelity of copying past a DNA lesion in a
      defined sequence on a synthetic oligonucleotide primer-template. The DNA product
      is the result of a complete lesion bypass reaction, i.e., containing all four
      deoxynucleotide triphosphates and requiring both insertion opposite the lesion
      and multiple extensions from the resulting primer termini containing the lesion.
      The nascent strand is recovered and hybridized to a gapped region of the
      lacZalpha complementation gene of the M13mp2 genome. When this DNA is introduced
      into Escherichia coli, errors made during translesion DNA synthesis are detected
      by M13 plaque colors. Sequencing of DNA from mutant plaques defines the types of
      errors and permits calculation of error rates for base substitutions, insertions,
      and deletions. The method is illustrated here for bypass of a cis-syn thymine
      thymine dimer by human DNA polymerase eta. The assay can be used with other
      lesions in various sequence contexts and with other polymerases with or without
      accessory proteins.

PMID- 16793380
TI  - DNA polymerases for translesion DNA synthesis: enzyme purification and mouse
      models for studying their function.
AB  - This chapter discusses experimental methods and protocols for the purification
      and preliminary characterization of DNA polymerases that are specialized for the
      replicative bypass (translesion DNA synthesis) of base or other types of DNA
      damage that typically arrest high-fidelity DNA synthesis, with particular
      emphasis on DNA polymerase kappa (Polkappa from mouse cells). It also describes
      some of the methods employed in the evaluation of mouse strains defective in
      genes that encode these enzymes.

PMID- 16793381
TI  - Purification and characterization of Escherichia coli DNA polymerase V.
AB  - Cell survival and genome rescue after UV irradiation in Escherichia coli depends
      on DNA repair mechanisms induced in response to DNA damage as part of the SOS
      regulon. SOS occurs in two phases. The first phase is dominated by accurate
      repair processes such as excision and recombinational DNA repair, while the
      second phase is characterized by a large approximately 100-fold increase in
      mutations caused by an error-prone replication of damaged DNA templates. SOS
      mutagenesis occurs as a direct result of the action of the UmuDC gene-products,
      which form the low fidelity Escherichia coli DNA polymerase V, a heterotrimeric
      complex composed of UmuD'(2)C. This chapter describes the preparation of highly
      purified native pol V that is suitable for a wide range of biochemical studies of
      protein-protein, protein-DNA interactions and translesion-synthesis (TLS)
      mechanisms.

PMID- 16793382
TI  - Yeast and human translesion DNA synthesis polymerases: expression, purification,
      and biochemical characterization.
AB  - The emergence of translesion DNA synthesis (TLS) as a primary mechanism by which
      eukaryotic cells tolerate DNA damage has led to a large effort to characterize
      the biochemical properties of the individual DNA polymerases and their roles in
      promoting replication past DNA lesions. The low-fidelity Y family DNA polymerases
      constitute a large proportion of TLS polymerases, and four of the five
      subfamilies of this class of polymerases are represented in eukaryotes. The
      eukaryotic B family DNA polymerase Polzeta also functions in TLS. We have had
      success in expressing and purifying these TLS polymerases from yeast cells,
      sometimes in milligram quantities. The purified proteins have been used to
      determine their ability to synthesize DNA on various modified templates and to
      analyze the kinetic efficiencies with which bypass occurs. Purified proteins have
      also been used to determine the X-ray crystal structures of several Y-family DNA
      polymerases. This chapter describes a general outline of methods used in our
      laboratory for the expression and purification of these TLS DNA polymerases from
      yeast cells and for assaying some of their biochemical properties.

PMID- 16793383
TI  - Localization of Y-family polymerases and the DNA polymerase switch in mammalian
      cells.
AB  - During translesion synthesis past sites of damaged DNA, specialized Y-family
      polymerases are employed by the cell to replace the high stringency replicative
      polymerases and synthesize DNA past the damaged site. These polymerases are
      localized in replication factories during the S phase of the cell cycle. When
      progress of the replication fork is blocked, the polymerase accessory protein,
      proliferating cell nuclear antigen (PCNA), becomes ubiquitinated and the
      monoubiquitinated PCNA has an increased affinity for Y-family DNA polymerase eta
      (poleta). This chapter describes methods for visualizing the polymerases in
      replication factories, for analyzing the ubiquitination status of PCNA, and for
      measuring its interaction with poleta in chromatin extracts.

PMID- 16793384
TI  - Repair of DNA double strand breaks: in vivo biochemistry.
AB  - Double strand breaks (DSBs) can cause damage to the genomic integrity of a cell
      as well as initiate genetic recombination processes. The HO and I-SceI
      endonucleases from budding yeast have provided a way to study these events by
      inducing a unique DSB in vivo under the control of a galactose-inducible
      promoter. The GAL::HO construct has been used extensively to study processes such
      as nonhomologous end joining, intra- and interchromosomal gene conversion, single
      strand annealing and break-induced recombination. Synchronously induced DSBs have
      also been important in the study of the DNA damage checkpoint, adaptation, and
      recovery pathways of yeast. This chapter describes methods of using GAL::HO to
      physically monitor the progression of events following a DSB, specifically the
      events leading to the switching of mating type by gene conversion of MAT using
      the silent donors at HML and HMR. Southern blot analysis can be used to follow
      the overall events in this process such as the formation of the DSB and product.
      Denaturing alkaline gels and slot blot techniques can be employed to follow the
      5' to 3' resection of DNA starting at the DSB. After resection, the 3' tail
      initiates a homology search and then strand invades its homologous sequence at
      the donor cassette. Polymerase chain reaction is an important means to assay
      strand invasion and the priming of new DNA synthesis as well as the completion of
      gene conversion. Methods such as chromatin immunoprecipitation have provided a
      means to study many proteins that associate with a DSB, including not only
      recombination proteins, but also proteins involved in nonhomologous end joining,
      cell cycle arrest, chromatin remodeling, cohesin function, and mismatch repair.

PMID- 16793385
TI  - Assays for nonhomologous end joining in extracts.
AB  - In mammalian cells, nonhomologous end-joining (NHEJ) repairs DNA double strand
      breaks created by ionizing radiation and V(D)J recombination. Using human whole
      cell extracts prepared by the method of Baumann and West (1998), we have
      described a cell-free system for NHEJ that joins both compatible and
      noncompatible DNA ends (Budman and Chu, 2005). To measure joining efficiency and
      assess the processing of DNA ends, we developed a quantitative polymerase chain
      reaction assay for the joining of two specific DNA ends. The in vitro NHEJ
      reaction recapitulates key features of NHEJ observed in vivo: end joining is
      dependent on DNA-PK and XRCC4/Ligase4, and noncompatible ends are processed by
      polymerase and nuclease activities that often stabilize the alignment of opposing
      ends by base pairing. This chapter describes methods for preparing whole cell
      extracts and for studying the NHEJ reaction in vitro.

PMID- 16793386
TI  - Purification and assays of Saccharomyces cerevisiae homologous recombination
      proteins.
AB  - Homologous recombination is an important means of eliminating DNA double strand
      breaks from chromosomes. The homologous recombination reaction is mediated by the
      Rad51 recombinase, which requires a number of ancillary factors for maximal
      efficiency. The development of purification procedures and biochemical assays for
      yeast Rad51 and other yeast recombination proteins has allowed investigators to
      begin dissecting the hierarchy of physical and functional interactions among
      these protein factors that govern the integrity of the homologous recombination
      machinery. The biochemical studies done with yeast recombination factors have
      helped formulate conceptual frameworks to guide similar endeavors in other
      eukaryotes, including humans. Continuing efforts with reconstituted systems that
      comprise yeast factors will undoubtedly continue to provide insights into the
      mechanistic intricacy of the homologous recombination machinery.

PMID- 16793387
TI  - Analysis of DNA recombination and repair proteins in living cells by
      photobleaching microscopy.
AB  - DNA double strand break repair through homologous recombination has been shown
      biochemically to require the coordinated action of the RAD52 group of proteins,
      including the DNA strand exchange protein Rad51. We have started to develop
      experimental tools to investigate the close cooperation of homologous
      recombination proteins in living cells, where proteins operate in the context of
      chromatin and in the presence of other nuclear processes. This chapter describes
      in detail methods to establish cell lines stably expressing green fluorescent
      protein -tagged recombination proteins and photobleaching techniques to
      investigate the behavior of the proteins with the use of live cell video
      microscopy. Fluorescence recovery after photobleaching (FRAP), fluorescence loss
      after photobleaching (FLIP), and their combination in the same cell are useful
      techniques to gain insights into the dynamic behavior of the recombination
      proteins. Parameters such as diffusion rates and mobile versus immobile fractions
      before and after DNA damage induction can be obtained. In addition, residence
      times of recombination proteins at sites of DNA damage can be determined. Through
      the application of FRAP and FLIP it is possible to establish whether proteins are
      present in the same multiprotein complex, whether this is affected by DNA damage
      induction, and whether proteins dynamically associate with and dissociate from
      sites of DNA damage.

PMID- 16793388
TI  - Synthetic junctions as tools to identify and characterize Holliday junction
      resolvases.
AB  - Genetic exchanges between chromosomes can lead to the formation of DNA
      intermediates known as Holliday junctions. The structure of these intermediates
      has been determined both biochemically and structurally, and their interactions
      with Holliday junction processing enzymes have been well characterized. A number
      of proteins, from both prokaryotic and eukaryotic sources, have been identified
      that promote the nucleolytic resolution of junctions. To facilitate these
      studies, synthetic DNA substrates that mimic true Holliday junctions have been
      developed. These now provide an important resource for both the identification
      and the characterization of novel Holliday junction resolvase activities. This
      chapter describes methods detailing the preparation and use of synthetic Holliday
      junctions and how they are best utilized in the study of proteins that might
      exhibit resolvase activity. Additionally, a method is described that can be used
      to rapidly screen a TAP-tagged library of proteins for resolvase activity without
      a need for conventional purification procedures.

PMID- 16793389
TI  - In vitro nonhomologous DNA end joining system.
AB  - The nonhomologous end joining (NHEJ) pathway is the major pathway that repairs
      DNA double strand breaks in multicellular eukaryotic organisms. Unlike homologous
      recombination, the NHEJ pathway utilizes minimal or no homology between the ends
      that need to be joined. Although the resulting NHEJ-repaired junctions can be
      diverse in sequence, they share a few common features, including frequent
      nucleolytic resection of the ends, near-random junctional additions, and
      utilization of microhomology. The in vitro NHEJ assay was developed in an attempt
      to recapitulate the joining of incompatible ends with purified core proteins and
      some additional factors. This in vitro system allows further understanding of the
      biochemical features of the pathway and evaluation of the functions of other
      proteins in NHEJ.

PMID- 16793390
TI  - RAG and HMGB1 proteins: purification and biochemical analysis of recombination
      signal complexes.
AB  - Two lymphoid cell-specific proteins, called RAG-1 and RAG-2, initiate the process
      of antigen receptor gene rearrangement, termed V(D)J recombination, by assembling
      a protein-DNA complex with two recombination signal sequences (RSSs), each of
      which adjoins a different receptor gene segment, and then introducing a DNA
      double strand break at the end of each RSS. The study of RAG-RSS complex assembly
      and activity has been facilitated by the development of methods to purify the RAG
      proteins and members of the HMG-box family of high mobility group proteins such
      as HMGB1 that promote RAG binding and cleavage activity in vitro. This chapter
      describes the purification of recombinant truncated and full-length RAG-1 and RAG
      2 expressed transiently in mammalian cells, as well as the purification of
      bacterially expressed full-length HMGB1. In addition, it details several
      experimental procedures used in our laboratory to study RAG-RSS complex formation
      and function in vitro.

PMID- 16793391
TI  - Purification and biochemical characterization of ataxia-telangiectasia mutated
      and Mre11/Rad50/Nbs1.
AB  - Ataxia-telangiectasia mutated (ATM) is a serine-threonine kinase that is
      activated by DNA double strand breaks to phosphorylate many cellular proteins
      involved in cell cycle regulation and DNA repair. We have shown previously that
      the activation of ATM can be reconstituted in an in vitro system using
      recombinant human ATM. In this system, ATM activity is dependent on the
      Mre11/Rad50/Nbs1 (MRN) complex and linear DNA, similar to requirements observed
      in human cells. This chapter describes methods used for the overexpression and
      purification of human ATM and MRN, as well as a protocol for in vitro kinase
      assays.

PMID- 16793392
TI  - Overproduction and purification of RFC-related clamp loaders and PCNA-related
      clamps from Saccharomyces cerevisiae.
AB  - The replication clamp PCNA and its loader RFC (Replication Factor C) are central
      factors required for processive replication and coordinated DNA repair. Recently,
      several additional related clamp loaders have been identified. These alternative
      clamp loaders contain the small Rfc2-5 subunits of RFC, but replace the large
      Rfc1 subunit by a pathway-specific alternative large subunit, Rad24 for the DNA
      damage checkpoint, Ctf18 for the establishment of sister chromatid cohesion, and
      Elg1 for a general function in chromosome stability. In order to define
      biochemical functions for these loaders, the loaders were overproduced in yeast
      and purified at a milligram scale. To aid in purification, the large subunit of
      each clamp loader was fused to a GST-tag that, after purification could be easily
      removed by a rhinoviral protease. This methodology yielded all clamp loaders in
      high yield and with high enzymatic activity. The yeast 9-1-1 checkpoint clamp,
      consisting of Rad17, Mec3, and Ddc1, was overproduced and purified in a similar
      manner.

PMID- 16793393
TI  - Functional assays for replication protein A (RPA).
AB  - Replication protein A (RPA) is a heterotrimeric, single-stranded DNA-binding
      protein. RPA is conserved in all eukaryotes and is essential for DNA replication,
      DNA repair, and recombination. RPA also plays a role in coordinating DNA
      metabolism and the cellular response to DNA damage. Assays have been established
      for many of these reactions. This chapter provides an overview of the methods
      used for analyzing RPA-DNA interactions, RPA-protein interactions, and functional
      activities of RPA. Methods are also discussed for visualizing RPA in the cell and
      analyzing the effects of RPA function on cell cycle progression in mammalian
      cells.

PMID- 16793394
TI  - Human DNA ligases I, III, and IV-purification and new specific assays for these
      enzymes.
AB  - The joining of DNA strand breaks by DNA ligases is required to seal Okazaki
      fragments during DNA replication and to complete almost all DNA repair pathways.
      In human cells, there are multiple species of DNA ligase encoded by the LIG1,
      LIG3, and LIG4 genes. Here we describe protocols to overexpress and purify
      recombinant DNA ligase I, DNA ligase IIIbeta, and DNA ligase IV/XRCC4 and the
      assays used to purify and distinguish between these enzymes. In addition, we
      describe a fluorescence-based ligation assay that can be used for high throughput
      screening of chemical libraries.

PMID- 16793395
TI  - Enzymatic mechanism of the WRN helicase/nuclease.
AB  - Werner syndrome (WS) is a premature aging disorder characterized by genomic
      instability and increased cancer risk (Martin, 1978). The WRN gene product
      defective in WS belongs to the RecQ family of DNA helicases (Yu et al., 1996).
      Mutations in RecQ family members BLM and RecQ4 result in two other disorders
      associated with elevated chromosomal instability and cancer, Bloom syndrome and
      Rothmund-Thomson syndrome, respectively (for review see Opresko et al., 2004a).
      RecQ helicase mutants display defects in DNA replication, recombination, and
      repair, suggesting a role for RecQ helicases in maintaining genomic integrity.
      The WRN gene encodes a 1,432 amino acid protein that has several catalytic
      activities (Brosh and Bohr, 2002) (Fig. 1). WRN is a DNA-dependent ATPase and
      utilizes the energy from ATP hydrolysis to unwind double-stranded DNA. WRN is
      also a 3' to 5' exonuclease, consistent with the presence of three conserved
      exonuclease motifs homologous to the exonuclease domain of Escherichia coli DNA
      polymerase I and RNase D. Most recently, WRN (Machwe et al., 2005) and other
      human RecQ helicases (Garcia et al., 2004; Machwe et al., 2005; Sharma et al.,
      2005) have been reported to possess an intrinsic single-strand annealing
      activity. In addition to its catalytic activities, WRN interacts with a number of
      proteins involved in various aspects of DNA metabolism. To understand the role of
      WRN in the maintenance of genome stability, a number of laboratories have
      undertaken a thorough characterization of its molecular and cellular functions.
      Here, we describe methods and approaches used for the functional and mechanistic
      analysis of WRN helicase or exonuclease activity. Protocols for measuring ATP
      hydrolysis, DNA binding, and catalytic unwinding or exonuclease activity of WRN
      protein are provided. Application of these procedures should enable the
      researcher to address fundamental questions regarding the biochemical properties
      of WRN or related helicases or nucleases, which would serve as a platform for
      further investigation of its molecular and cellular functions.

PMID- 16793396
TI  - Analysis of the DNA unwinding activity of RecQ family helicases.
AB  - The RecQ family of DNA helicases is highly conserved in evolution from bacteria
      to mammals. There are five human RecQ family members (RECQ1, BLM, WRN, RECQ4 and
      RECQ5), defects, three of which give rise to inherited human disorders. Mutations
      of BLM have been identified in patients with Bloom's syndrome, WRN has been shown
      to be mutated in Werner's syndrome, while mutations of RECQ4 have been associated
      with at least a subset of cases of both Rothmund-Thomson syndrome and RAPADILINO.
      The most characteristic features of these diseases are a predisposition to the
      development of malignancies of different types (particularly in Bloom's
      syndrome), some aspects of premature aging (particularly in Werner's syndrome),
      and on the cellular level, genome instability. In order to gain understanding of
      the molecular defects underlying these diseases, many laboratories have focused
      their research on a study of the biochemical properties of human RecQ helicases,
      particularly those associated with disease, and of RecQ proteins from other
      organisms (e.g., Sgs1p of budding yeast, Rqh1p of fission yeast, and RecQ of
      E.coli). In this chapter, we summarize the assay systems that we employ to
      analyze the catalytic properties of the BLM helicase. We have successfully used
      these methods for the study of other RecQ and non-RecQ helicases, indicating that
      they are likely to be applicable to all helicases.

PMID- 16793397
TI  - Characterization of checkpoint responses to DNA damage in Saccharomyces
      cerevisiae: basic protocols.
AB  - In spite of certain special features of its cell cycle, the yeast Saccharomyces
      cerevisiae has proved to be an excellent and widely used model to study
      eukaryotic checkpoint responses to DNA damage. This chapter primarily summarizes
      selected cytological methods that are useful for initial characterization of cell
      cycle responses. These can be useful in order to study mutants, conditions, or
      selected DNA damaging agents and experimental examples are given. We have also
      included protocols for flow-cytometric cell cycle analysis and for determination
      of Rad53 phosphorylation, a commonly used indicator of checkpoint activation.

PMID- 16793398
TI  - Recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes to DNA damage.
AB  - The ATR (ataxia-telangiectasia mutated and rad3-related)-ATRIP (ATR-interacting
      protein) kinase complex plays a central role in the checkpoint responses to a
      variety of types of DNA damage, especially those interfering with DNA
      replication. The checkpoint-signaling pathway activated by ATR-ATRIP regulates
      and coordinates cell-cycle progression, DNA replication, DNA repair, and many
      other cellular processes critical for genomic stability. Upon DNA damage or DNA
      replication interference, ATR-ATRIP and two of its key regulators, the Rad17 and
      the 9-1-1 complexes, are localized to sites of DNA damage and stalled replication
      forks. Recent biochemical and cell biological studies have revealed that RPA
      coated single-stranded DNA, a common structure generated at sites of DNA damage
      and stalled replication forks, plays crucial roles in the recruitment of ATR
      ATRIP, Rad17, and 9-1-1 complexes. The recruitment of ATR-ATRIP and its
      regulators to DNA damage is a key step for the recognition of DNA damage by the
      checkpoint, and is likely important for the regulation of ATR activity and/or
      function in response to DNA damage. The methods used to characterize the DNA
      association of ATR-ATRIP, Rad17, and 9-1-1 complexes have laid a foundation for
      further biochemical studies, which may ultimately lead us to understand the
      molecular mechanisms by which ATR-ATRIP monitors and protects genomic integrity.

PMID- 16793399
TI  - Multiple approaches to study S. cerevisiae Rad9, a prototypical checkpoint
      protein.
AB  - The Saccharomyces cerevisiae RAD9 checkpoint gene is the prototypical checkpoint
      gene and is required for efficient checkpoint regulation in late G1, S, and at
      the G2/M cell cycle transition following DNA damage. Rad9 is required for the
      activation of Rad53 after damage and has been proposed to have roles in lesion
      recognition as well as DNA repair and the maintenance of genome stability. Here
      we describe methodology suitable for the study of G1, intra-S, and G2/M
      checkpoints in budding yeast, the analysis of Rad9/Rad53 phospho-forms, the
      biochemical analysis of Rad9 and Rad53, the fractionation of soluble and
      chromatin associated proteins, including Rad9, and the live cell imaging of GFP
      tagged Rad9.

PMID- 16793400
TI  - Methods for studying adaptation to the DNA damage checkpoint in yeast.
AB  - When yeast are faced with irreparable DNA damage, they will first arrest in G2/M,
      via the DNA damage checkpoint pathway, but will subsequently adapt to that arrest
      and resume division. Here, we summarize assays that we have used to examine
      checkpoint adaptation. Specifically, we discuss the merits of inducing DNA damage
      with ionizing radiation (IR) and IR-mimetic drugs, HO, and the cdc13-1 mutation.
      We also discuss readouts that we have used to visualize adaptation.

PMID- 16793401
TI  - DNA damage-induced phosphorylation of Rad55 protein as a sentinel for DNA damage
      checkpoint activation in S. cerevisiae.
AB  - Rad55 protein is one of two Rad51 paralogs in the budding yeast Saccharomyces
      cerevisiae and forms a stable heterodimer with Rad57, the other Rad51 paralog.
      The Rad55-Rad57 heterodimer functions in homologous recombination during the
      assembly of the Rad51-ssDNA filament, which is central for homology search and
      DNA strand exchange. Previously, we identified Rad55 protein as a terminal target
      of the DNA damage checkpoints, which coordinate the cellular response to
      genotoxic stress. Rad55 protein phosphorylation is signaled by a significant
      electrophoretic shift and occurs in response to a wide range of genotoxic stress.
      Here, we map the phosphorylation site leading to the electrophoretic shift and
      show that Rad55 protein is a bona fide direct in vivo substrate of the central
      DNA damage checkpoint kinase Mec1, the budding yeast equivalent of human ATM/ATR.
      We provide protocols to monitor the Rad55 phosphorylation status in vivo and
      assay Rad55-Rad57 phosphorylation in vitro using purified substrate with the Mec1
      and Rad53 checkpoint kinases.

PMID- 16793402
TI  - Methods for studying mutagenesis and checkpoints in Schizosaccharomyces pombe.
AB  - Mutations in genome caretaker genes can induce genomic instability, which are
      potentially early events in tumorigenesis. Cells have evolved biological
      processes to cope with the genomic insults. One is a multifaceted response,
      termed checkpoint, which is a network of signaling pathways to coordinate cell
      cycle transition with DNA repair, activation of transcriptional programs, and
      induction of tolerance of the genomic perturbations. When genomic perturbations
      are beyond repair, checkpoint responses can also induce apoptosis or senescence
      to eliminate those deleterious damaged cells. Fission yeast, Schizosaccharomyces
      pombe (S. pombe) has served as a valuable model organism for studies of the
      checkpoint signaling pathways. In this chapter, we describe methods used to
      analyze mutagenesis and recombinational repair induced by genomic perturbations,
      and methods used to detect the checkpoint responses to replication stress and DNA
      damage in fission yeast cells. In the first section, we present methods used to
      analyze the mutation rate, mutation spectra, and recombinational repair in
      fission yeast when replication is perturbed by either genotoxic agents or
      mutations in genomic caretaker gene such as DNA replication genes. In the second
      section, we describe methods used to examine checkpoint activation in response to
      chromosome replication stress and DNA damage. In the final section, we comment on
      how checkpoint activation regulates mutagenic synthesis by a translesion DNA
      polymerase in generating a mutator phenotype of small sequence alterations in
      cells, and how a checkpoint kinase appropriately regulates an endonuclease
      complex to either prevent or allow deletion of genomic sequences and
      recombinational repair when fission yeast cells experience genomic perturbation
      in order to avoid deleterious mutations and maintain cell growth.

PMID- 16793403
TI  - Methods for determining spontaneous mutation rates.
AB  - Spontaneous mutations arise as a result of cellular processes that act upon or
      damage DNA. Accurate determination of spontaneous mutation rates can contribute
      to our understanding of these processes and the enzymatic pathways that deal with
      them. The methods that are used to calculate mutation rates are based on the
      model for the expansion of mutant clones originally described by Luria and
      Delbruck (1943) and extended by Lea and Coulson (1949). The accurate
      determination of mutation rates depends on understanding the strengths and
      limitations of these methods and how to optimize a fluctuation assay for a given
      method. This chapter describes the proper design of a fluctuation assay, several
      of the methods used to calculate mutation rates, and ways to evaluate the results
      statistically.

PMID- 16793404
TI  - Genomic approaches for identifying DNA damage response pathways in S. cerevisiae.
AB  - DNA damage response pathways have been studied extensively in the budding yeast
      Saccharomyces cerevisiae, yet new genes with roles in the DNA damage response are
      still being identified. In this chapter we describe the use of functional genomic
      approaches in the identification of DNA damage response genes and pathways. These
      techniques take advantage of the S. cerevisiae gene deletion mutant collection,
      either as an ordered array or as a pool, and can be automated for high
      throughput.

PMID- 16793405
TI  - Techniques for gamma-H2AX detection.
AB  - When a double-strand break (DSB) forms in DNA, many molecules of histone H2AX
      present in the chromatin flanking the break site are rapidly phosphorylated. The
      phosphorylated derivative of H2AX is named gamma-H2AX, and the phosphorylation
      site is a conserved serine four residues from the C-terminus, 139 in mammals and
      129 in budding yeast. An antibody to gamma-H2AX reveals that the molecules form a
      gamma-focus at the DSB site. The gamma-focus increases in size rapidly for 10-30
      min after formation, and remains until the break is repaired. Studies have
      revealed that small numbers of gamma-foci are present in cells even without the
      purposeful introduction of DNA DSBs. These cryptogenic foci increase in number
      during senescence in culture and aging in mice. This chapter presents techniques
      for revealing gamma-H2AX foci in cultured cells, in metaphase spreads from
      cultured cells, in tissues, and in yeast.

PMID- 16793406
TI  - Methods for studying the cellular response to DNA damage: influence of the Mre11
      complex on chromosome metabolism.
AB  - Dramatic progress in understanding the mediators and mechanisms of chromosome
      break metabolism has been made in recent years. As a result, the links between
      disease and defects in chromosome dynamics have become clearer. In this chapter,
      we discuss techniques employed in our laboratory to study chromosome break
      metabolism, which include assessments at the molecular and cellular level. In our
      laboratory, we use the Mre11 complex as a tool to study this process, but the
      techniques discussed are of general relevance.

PMID- 16793407
TI  - Detecting repair intermediates in vivo: effects of DNA damage response genes on
      single-stranded DNA accumulation at uncapped telomeres in budding yeast.
AB  - Single-stranded DNA (ssDNA) is an important intermediate in many DNA repair
      pathways. Here we describe protocols that permit the measurement of ssDNA that
      has arisen in the yeast genome in vivo, in response to telomere uncapping. Yeast
      strains defective in DNA damage response (DDR) genes can be used to infer the
      roles of the corresponding proteins in regulating ssDNA production and in
      responding to ssDNA. Using column based methods to purify yeast genomic DNA and
      quantitative amplification of single-stranded DNA (QAOS) it is possible to
      measure ssDNA at numerous single copy loci in the yeast genome. We describe how
      to measure ssDNA in synchronous cultures of cdc13-1 mutants, containing a
      temperature sensitive mutation in an essential telomere capping protein, and in
      asynchronous cultures of yku70Delta mutants also defective in telomere capping.

PMID- 16793408
TI  - Analysis of non-B DNA structure at chromosomal sites in the mammalian genome.
AB  - Changes at sites of genetic instability ultimately involve DNA repair pathways.
      Some sites of genetic instability in the mammalian genome appear to be unstable
      because they adopt a non-B DNA conformation. We describe two structural
      approaches for determination of whether a genomic region is configured in a non-B
      DNA conformation. Our studies indicate that at least some chromosomal fragile
      sites can be explained by such altered DNA conformations. One of the methods that
      we describe is called the bisulfite modification assay. This is a powerful assay
      because it provides information on individual DNA molecules. The second approach
      uses preexisting DNA structural reagents, but describes our specific application
      of them to analysis of DNA in vivo.

PMID- 16793410
TI  - The delitto perfetto approach to in vivo site-directed mutagenesis and chromosome
      rearrangements with synthetic oligonucleotides in yeast.
AB  - In vivo genome manipulation through site-directed mutagenesis and chromosome
      rearrangements has been hindered by the difficulty in achieving high frequencies
      of targeting and the intensive labor required to create altered genomes that do
      not contain any heterologous sequence. Here we describe our approach, referred to
      as delitto perfetto, that combines the versatility of synthetic oligonucleotides
      for targeting with the practicality of a general selection system. It provides
      for an enormously wide variety of genome modifications via homologous
      recombination. Exceptional high frequencies of mutations are reached when a site
      specific double-strand break (DSB) is induced within the locus targeted by the
      synthetic oligonucleotides. Presented in this chapter is an in-depth description
      of a series of applications of the delitto perfetto strategy for mutagenesis and
      chromosome modification both with and without the induction of a DSB, along with
      the procedures and materials.

PMID- 16793409
TI  - Detection and structural analysis of R-loops.
AB  - R-loops are structures where an RNA strand is base paired with one DNA strand of
      a DNA duplex, leaving the displaced DNA strand single-stranded. Stable R-loops
      exist in vivo at prokaryotic origins of replication, the mitochondrial origin of
      replication, and mammalian immunoglobulin (Ig) class switch regions in activated
      B lymphocytes. All of these R-loops arise upon generation of a G-rich RNA strand
      by an RNA polymerase upon transcription of a C-rich DNA template strand. These R
      loops are of significant length. For example, the R-loop at the col E1 origin of
      replication appears to be about 140 bp. Our own lab has focused on class switch
      regions, where the R-loops can extend well over a kilobase in length. Here,
      methods are described for detection and analysis of R-loops in vitro and in vivo.

PMID- 16793411
TI  - Assays for transcriptional mutagenesis in active genes.
AB  - Cells exposed to DNA-damaging agents in their natural environment do not undergo
      continuous cycles of replication but are more frequently engaged in gene
      transcription. Despite the relatively high efficiency of the different DNA repair
      pathways, some lesions remain in DNA. During transcription, RNA polymerase can
      bypass DNA damage on the transcribed strand of an active gene. This bypass can be
      at the origin of the production of "mutated" mRNA because of the transcriptional
      miscoding (transcriptional mutagenesis) due to the altered pairing specificities
      of the lesion. In vivo consequences of transcriptional mutagenesis on normal cell
      physiology have not well been documented because of the lack of a robust system
      allowing for its study. We describe here a procedure that we developed using a
      plasmid-based luciferase reporter assay to analyze the transcriptional
      mutagenesis events induced by different types of DNA lesions. Introduction of the
      DNA lesion to be studied at a specific site on the plasmid is based on the
      synthesis of a complementary strand of a circular, single-stranded DNA (ssDNA)
      from a DNA lesion-containing oligonucleotide. Once obtained, this construct can
      be transformed into different Escherichia coli strains that can express the
      luciferase gene under nongrowth conditions. Quantification of luciferase activity
      and sequencing of luciferase cDNAs allow for the characterization of
      transcriptional mutagenesis both quantitatively and qualitatively.

PMID- 16793412
TI  - Methods for studying chromatin assembly coupled to DNA repair.
AB  - In the eukaryotic nucleus, the DNA repair machinery operates on chromatin
      embedded DNA substrates. Currently, a favored model for DNA repair into chromatin
      involves the transient disruption of chromatin organization to facilitate access
      of the repair machinery to DNA lesions. Importantly, this model implies that, in
      addition to DNA repair, a subsequent step is necessary to restore a proper
      chromatin structure. To study this latter step, we describe here methods for
      simultaneously analyzing chromatin assembly and DNA repair both in vitro and in
      vivo. Several cell-free systems have been developed that reproduce both DNA
      repair and nucleosome assembly. These in vitro systems are based on the use of
      defined damaged DNA. Two complementary assays are routinely used: (i) with
      circular DNA molecules, one can monitor in a combined analysis both repair
      synthesis and plasmid supercoiling; (ii) with immobilized damaged DNA, one
      follows specific protein interactions including histone deposition. In addition,
      in vivo assays have been designed to monitor the recruitment of chromatin
      assembly factors onto damaged chromatin either at a global level over the whole
      cell nucleus or locally at sites of DNA damage. Combination of these approaches
      provides powerful tools to gain insights into the mechanism by which chromatin
      organization can be restored after repair of DNA lesions.

PMID- 16793413
TI  - Structure-function analysis of SWI2/SNF2 enzymes.
AB  - Biochemical and structural progress over the last years has revealed that
      SWI2/SNF2 family chromatin remodeling or DNA repair enzymes are molecular motors
      that transport duplex DNA along a helicase-like domain using ATP-hydrolysis. The
      screw motion of DNA along the active site probably generates the force to disrupt
      chromatin or other protein:DNA complexes. In this chapter, we describe
      biochemical and structural approaches to study the molecular mechanism of
      SWI2/SNF2 enzymes. In particular, we describe assays to monitor DNA dependent
      ATPase activity, translocation on duplex DNA, and DNA distortion activity. We
      also describe recent progress in the crystallization and structure determination
      of SWI2/SNF2 enzymes in complex with duplex DNA.

PMID- 16793414
TI  - Genomic approach for the understanding of dynamic aspect of chromosome behavior.
AB  - Various functions are integrated into a single chromosome molecule. The genomic
      approach (ChIP-chip) we introduce here is a very powerful tool to study dynamic
      changes of the structure and function of the chromosome at the level of protein
      DNA interaction as precisely as possible without prejudice or bias. This
      technology opens up the way to understand how local protein-protein or protein
      DNA interactions lead to the dynamic changes of chromosome structure and how
      various chromosomal functions are connected to make a network for the faithful
      maintenance of the genome.

PMID- 16793415
TI  - Measurement of chromosomal DNA single-strand breaks and replication fork
      progression rates.
AB  - Chromosomal single-strand breaks (SSBs) are the most common lesions arising in
      cells, but are normally rapidly repaired by multiprotein complexes centered
      around the scaffold protein, XRCC1. Here, we describe protocols to measure
      chromosomal SSBs in cells and for recovering and identifying novel components of
      SSBR complexes in vitro and in vivo. We also describe an assay we employ to
      measure the rate of replication fork progression in mammalian/vertebrate cells in
      the presence or absence of DNA damage.

PMID- 16793416
TI  - Monitoring DNA replication following UV-induced damage in Escherichia coli.
AB  - The question of how the replication machinery accurately copies the genomic
      template in the presence of DNA damage has been intensely studied for more than
      forty years. A large number of genes has been characterized that, when mutated,
      are known to impair the ability of the cell to replicate in the presence of DNA
      damage. This chapter describes three techniques that can be used to monitor the
      progression, degradation, and structural properties of replication forks
      following UV-induced DNA damage in Escherichia coli.

PMID- 16793417
TI  - Methods to study replication fork collapse in budding yeast.
AB  - Replication of the eukaryotic genome is a difficult task, as cells must
      coordinate chromosome replication with chromatin remodeling, DNA recombination,
      DNA repair, transcription, cell cycle progression, and sister chromatid cohesion.
      Yet, DNA replication is a potentially genotoxic process, particularly when
      replication forks encounter a bulge in the template: forks under these conditions
      may stall and restart or even break down leading to fork collapse. It is now
      clear that fork collapse stimulates chromosomal rearrangements and therefore
      represents a potential source of DNA damage. Hence, the comprehension of the
      mechanisms that preserve replication fork integrity or that promote fork collapse
      are extremely relevant for the understanding of the cellular processes
      controlling genome stability. Here we describe some experimental approaches that
      can be used to physically visualize the quality of replication forks in the yeast
      S. cerevisiae and to distinguish between stalled and collapsed forks.

PMID- 16793418
TI  - Analysis of gross-chromosomal rearrangements in Saccharomyces cerevisiae.
AB  - Cells utilize numerous DNA metabolic pathways and cell-cycle checkpoints to
      maintain the integrity of their genome. Failure of these mechanisms can lead to
      genome instability, abnormal cell proliferation, and cell death. This chapter
      describes a method for the measurement of the rate of accumulating gross
      chromosomal rearrangements (GCRs) in haploid cells of the yeast Saccharomyces
      cerevisiae. The isolation of cells with GCRs relies on the simultaneous loss of
      two counterselectable markers, CAN1 and URA3, within a nonessential region on the
      left arm of chromosome V. Healing of DNA breaks by de novo telomere addition,
      translocations, large interstitial deletions, and chromosome fusion has been
      detected using a PCR-based procedure for the mapping and amplification of
      breakpoint junctions, which is also described in detail here. This GCR analysis
      provides an effective tool for the assessment of the contribution by multiple
      cellular mechanisms to the maintenance of genome integrity.

PMID- 16793419
TI  - Formation and processing of stalled replication forks--utility of two-dimensional
      agarose gels.
AB  - Replication forks can be stalled by tightly bound proteins, DNA damage,
      nucleotide deprivation, or defects in the replication machinery. It is now
      appreciated that processing of stalled replication forks is critical for
      completion of DNA replication and maintenance of genome stability. In this
      chapter, we detail the use of two-dimensional (2D) agarose gels with Southern
      hybridization for the detection and analysis of blocked replication forks in
      vivo. This kind of 2D gel electrophoresis has been used extensively for analysis
      of replication initiation mechanisms for many years, and more recently has become
      a valuable tool for analysis of fork stalling. Although the method can provide
      valuable information when forks are stalled in random locations (e.g., after UV
      damage or nucleotide deprivation), it is even more informative with site-specific
      fork blockage, for example, blocks caused by tightly bound replication terminator
      proteins or by drug-stabilized topoisomerase cleavage complexes.

PMID- 16793420
TI  - Poly(ADP-ribose) polymerase-1 activation during DNA damage and repair.
AB  - Changes in chromatin structure emanating from DNA breaks are among the most
      initiating events in the damage response of the cell. In higher eukaryotes,
      poly(ADP-ribose) polymerase-1 (PARP-1) translates the occurrence of DNA breaks
      detected by its zinc-finger domain into a signal, poly ADP-ribose, synthesized
      and amplified by its DNA-damage dependent catalytic domain. This epigenetic mark
      on chromatin, induced by DNA discontinuities, is now considered as a part of a
      survival program aimed at protecting primarily chromatin integrity and stability.
      In this chapter we describe some of our methods for determining in vivo and in
      vitro PARP-1 activation in response to DNA strand breaks. Poly(ADP-ribosyl)ation
      is a posttranslational modification of nuclear proteins induced by DNA strand
      breaks that contributes to the survival of injured proliferating cells (D'Amours
      et al., 1999). Poly(ADP-ribose) polymerases (PARPs) now constitute a large family
      of 18 proteins, encoded by different genes and displaying a conserved catalytic
      domain in which PARP-1 (113 kDa), the founding member, and PARP-2 (62 kDa) are so
      far the sole enzymes whose catalytic activity is immediately stimulated by DNA
      strand-breaks (Ame et al., 2004). PARP-1 fulfils several key functions in
      repairing an interruption of the sugar phosphate backbone. It efficiently detects
      the presence of a break by its N-terminal zinc-finger domain; the occurrence of a
      break is immediately translated into a posttranslational modification of histones
      H1 and H2B leading to chromatin structure relaxation and therefore to increased
      DNA accessibility. As an amplified DNA damage signal, auto-poly(ADP-ribosyl)ation
      of PARP-1 triggers the recruitment of XRCC1, which coordinates and stimulates the
      repair process, to the DNA damage sites in less than 15 s in living cells (Okano
      et al., 2003). Although dispensable in a test tube DNA repair experiment, in vivo
      these three properties positively influence the overall kinetics of a DNA damage
      detection/signaling pathway leading rapidly to the resolution of DNA breaks.
      Accordingly, poly ADP-ribose (PAR) synthesis and the accompanying NAD consumption
      are now considered as bona fide marks of DNA interruptions in the genome. In this
      chapter we describe several methods for determining PARP activation in response
      to the occurrence of DNA breaks in vitro and in vivo.

PMID- 16793421
TI  - Tyrosyl-DNA phosphodiesterase (Tdp1) (3'-phosphotyrosyl DNA phosphodiesterase).
AB  - Tyrosyl-DNA phosphodiesterase (Tdp1) hydrolyzes 3'-phosphotyrosyl bonds in vitro.
      Because topoisomerase I, a type IB topoisomerase, is the only enzyme known to
      form 3'-phosphotyrosine bonds in eukaryotic cells, it was proposed that Tdp1 is
      involved in the repair of dead-end topoisomerase I-DNA covalent complexes that
      may form in vivo. It has also been proposed that Tdp1 may represent a novel
      anticancer target since known anticancer agents (e.g., camptothecin) act by
      stabilizing topoisomerase I-DNA covalent adducts. The importance of Tdp1 in DNA
      repair is also demonstrated by the observation that a recessive mutation in the
      human TDP1 gene is responsible for the hereditary disorder Spinocerebellar Ataxia
      with Axonal Neuropathy (SCAN). Although it has been proposed that Tdp1 may be
      involved in the repair of multiple DNA lesions, this chapter describes the
      synthesis and characterization of substrates used to study the role of Tdp1 in
      repairing topoisomerase I-DNA adducts, and the methods used to study the
      catalytic mechanism and structure of this novel enzyme.

PMID- 16793422
TI  - Assaying double-strand break repair pathway choice in mammalian cells using a
      targeted endonuclease or the RAG recombinase.
AB  - DNA damage repair is essential for the maintenance of genetic integrity in all
      organisms. Unrepaired or imprecisely repaired DNA can lead to mutagenesis, cell
      death, or malignant transformation. DNA damage in the form of double-strand
      breaks (DSBs) can occur as a result of both exogenous insults, such as ionizing
      radiation and drug therapies, and normal metabolic processes including V(D)J
      recombination. Mammalian cells have multiple pathways for repairing DSBs,
      including nonhomologous end-joining (NHEJ), homologous recombination (HR), and
      single-strand annealing (SSA). This chapter describes the use of reporter
      substrates for assaying the contributions of these pathways to DSB repair in
      mammalian cells, in particular murine embryonic stem cells. The individual
      contributions of NHEJ, HR, and SSA can be quantified using fluorescence and PCR
      based assays after the precise introduction of DSBs either by the I-SceI
      endonuclease or by the RAG recombinase. These reporters can be used to assess the
      effects of genetic background, dominant-negative constructs, or physiological
      conditions on DSB repair in a wide variety of mammalian cells.

PMID- 16793425
TI  - Sodium nitrite as a therapeutic agent for central nervous system diseases.

PMID- 16793428
TI  - Wilbrand's knee: does it exist?
AB  - OBJECTIVE: In 1904, Hermann Wilbrand reported that nasal ON fibers form a loop
      into the contralateral ON, subsequently referred to as Wilbrand's knee. He had
      further theorized that a lesion affecting Wilbrand's knee would develop a
      distinct visual field defect characterized by an ipsilateral central scotoma with
      a contralateral superotemporal visual field defect. We present clinical evidence
      that disputes the existence of Wilbrand's knee. METHODS: A retrospective analysis
      of 3 patients whose ONs were divided at the ON-chiasm junction is presented. Two
      patients had an ONS meningioma and the other patient had sarcoidosis of the ON.
      Resection of the lesion and the ON up to the nerve-chiasm junction was done to
      prevent the disease from extending into the OC and the contralateral ON. The
      patients had detailed neuro-ophthalmologic evaluations preoperatively and
      postoperatively. RESULTS: After the resection of the ON at the ON-chiasm junction
      in the 3 patients, junctional scotoma could not be detected by visual perimetry.
      CONCLUSION: No clinical perimetric evidence was found to support the existence of
      Wilbrand's knee in the anterior visual pathway.

PMID- 16793430
TI  - The pathophysiologic mechanism of cerebellar mutism.
AB  - OBJECTIVE: Cerebellar mutism (CM) is a postoperative complication of mainly
      pediatric posterior fossa surgery. Multiple theories exist for explaining this
      phenomenon. We have made an attempt to further understand this entity given a
      particularly interesting case as it relates to multiple pathophysiologic
      pathways. METHODS: We have reviewed the details surrounding a particularly
      interesting case of CM. A retrospective analysis of this patient's clinical
      history and recovery is described. An extensive literature review has been
      performed in conjunction with an attempt to help elucidate details and a better
      understanding of CM. RESULTS: A thorough analysis of existing theories as to the
      pathophysiologic mechanism of CM has been performed as it relates to the details
      of this particular case. A case is described in which a child exhibiting CM
      abruptly improved and made a relatively quick recovery after the triggering of
      the melodic speech pathway by way of watching and beginning to sing along with a
      video. It appears that this incident involving a familiar song catalyzed various
      speech pathways, which apparently were in some state of shock. This phenomenon
      seems to be a temporary entity involving not only the mechanical coordination of
      speech production, but also the initiation of speech itself. CONCLUSIONS:
      Evidence exists for a pathophysiologic pathway for speech by way of coordinating
      phonation and articulation. In addition, there seems to exist a pathway by which
      the initiation of speech may be altered or halted by posterior fossa pathology,
      namely, vermian or dentate nuclear injury. In particular to this case, we found
      that the incidental appreciation of other forms of speech, melodic in this
      instance, may be the key to help stimulate and accelerate the recovery from CM.

PMID- 16793431
TI  - A prospective analysis of 151 cases of patients with acromegaly operated by one
      neurosurgeon: a follow-up of more than 23 years.
AB  - BACKGROUND: Transsphenoidal adenomectomy has been the accepted surgical
      management for treatment of growth hormone (GH)-secreting pituitary adenomas.
      Although the goal of treatment might be to keep the GH level in the reference
      range, the actual definition of success in control of acromegaly is not yet
      clear. METHODS: The aim of this study was to analyze prospectively the result of
      transsphenoidal adenoctomy performed over 23-year period by a single neurosurgeon
      in one center. The analysis has been performed to determine which preoperative
      factor could significantly influence the long term outcome. This series consisted
      of 151 patients. The preoperative hormonal studies documenting the high GH and/or
      insulin-like growth factor were available in all the cases. At least 1 laboratory
      report documenting the postoperative level of hormones was also available for all
      of them. Transsphenoidal microsurgical adenomectomy was performed in all the
      cases. RESULTS: There were 90 patients with pure GH-secreting adenoma (59.6%)
      with the highest GH level of 235 mU/L. A second group of 12 patients had normal
      GH level but elevated serum level of insulin-like growth factor 1 (8%). The group
      with mixed secretion of GH and prolactin included 49 cases (32.4%). There was no
      postoperative mortality. Cerebrospinal fluid leakage occurred in 12 patients.
      Transient diabetes insipidus was encountered in 19 cases (12.6%) and long lasting
      diabetes insipidus in 2 patients (1.3%). Early and minor hypopituitarism was
      encountered in 14 patients, whereas a persistent condition occurred mainly after
      irradiation in 14 other cases. Normal postoperative serum GH level could be
      achieved in 98 patients (94.2%) of 104 cases with full follow-up. CONCLUSION: In
      the developing countries, early diagnosis and proper surgical extirpation of the
      GH-secreting adenoma by an experienced and dedicated pituitary surgeon is
      mandatory to reduce the mortality and increase the chance of cure of this rather
      mortal endocrionopathy.

PMID- 16793433
TI  - Surgical treatment of trigeminal neuralgia without vascular compression: 20 years
      of experience.
AB  - BACKGROUND: There are few reports on the outcome of surgical treatment of TGN
      without vascular compression. METHODS: Between 1984 and 2004, 668 patients
      underwent MVD for TGN. In 21 patients (3.1%), vascular compression was absent.
      The surgical strategy in these cases involved the following: (1) dissection and
      exposure of the entire trigeminal nerve root; (2) slight neurapraxia with bipolar
      tips at the trigeminal nerve root; and (3) isolation of trigeminal nerve with
      Teflon sponge fragments. RESULTS: The patients' (female/male, 20:1) ages ranged
      from 33 to 77 years. Their right side was the most frequently involved (61.9%).
      Their mean duration of pain before treatment was 7.6 years (range = 1-20 years).
      At surgical exploration, vascular compression or anatomical abnormalities were
      absent in 15 patients (71.4%), arachnoidal thickening was present in 5 (23.8%),
      and fiber dissociation of the trigeminal nerve was present in 1 (4.8%). Mean
      follow-up after surgery was 17.7 months (range = 4-65 months). Immediate relief
      from pain occurred in all 21 patients. On Kaplan-Meier analysis, recurrence was
      maintained at 14.8% for 12, 24, and 36 months, increasing to 43.2% at 48 months.
      Permanent hypoesthesia was present in 6 patients (28.6%), whereas loss of corneal
      reflex was observed transiently in 1 (4.8%). Motor function of the trigeminal
      nerve was intact in all patients. No other complication was found. CONCLUSION:
      The proposed surgical plan of standard MVD plus slight trigeminal nerve root
      neurapraxia is a safe and effective management option for TGN without vascular
      compression.

PMID- 16793435
TI  - Tuberculum sellae meningiomas: functional outcome in a consecutive series treated
      microsurgically.
AB  - OBJECTIVE: The objective of this study was to analyze a series of patients
      harboring a tuberculum sellae meningioma with regard to clinical presentation and
      long-term functional outcome. METHODS: Data in a consecutive series of 62
      patients harboring a tuberculum sellae meningioma treated microsurgically between
      1990 and 2003 were retrospectively reviewed. RESULTS: The mean age of the 46
      women and 16 men enrolled in the study was 53 years (range = 29-81 years). The
      presenting symptom was visual compromise in 87.1% of the patients, and
      examination revealed decreased visual acuity in 79% and impaired visual fields in
      64.5% of the patients. In addition, 14.5% of the patients had preoperative
      hormonal abnormalities. Simpson grades I and II resections, usually via a
      pterional approach, were achieved in 90.3% of the patients. Postoperatively,
      vision improved in 53.2%, remained unchanged in 29.8%, and deteriorated in 17.0%
      of the patients. The intraoperative finding predicting an unfavorable visual
      outcome was a thin atrophic optic nerve, encasement of the nerve, or tumor
      adhesion to its undersurface. Of the patients, 12.9% required permanent
      postoperative hormonal replacement. After a mean follow-up period of 6.0 years
      (range = 18 months-14 years), 88.7% of the patients resumed normal life activity
      and 2 recurrent tumors were observed (3.2%) and reoperated. CONCLUSIONS:
      Preoperative magnetic resonance imaging provides reliable information with regard
      to dislocation of critical vascular structures. However, the relationship between
      optic nerves and tumors (eg, adhesion and encasement) affected postoperative
      results and can only be fully appreciated during microsurgery. Visual outcome may
      be improved by preserving the microvasculature supplying the optic apparatus.

PMID- 16793438
TI  - Sellar floor reconstruction after transsphenoidal surgery using fibrin glue
      without grafting or implants: technical note.
AB  - BACKGROUND: Different techniques have already been described for reconstructing
      the sellar floor after transsphenoidal (TS) procedures. This paper reports on the
      use of fibrin glue alone without grafting or the use of implants in the
      reconstruction of the sellar floor after TS. METHODS: Five hundred sixty-seven
      patients who submitted to TS for pituitary and sellar region tumors were studied.
      No intraoperative cerebrospinal fluid (CSF) leak occurred in 503 patients (group
      1); in the remaining 64 patients (group 2), intraoperative CSF leak was noted. In
      group 1 patients, closure of the sellar floor consisted of packing the surgical
      bed with hemostatic material only. When CSF leak was noted, the surgical bed was
      covered with a layer of hemostatic material and the intrasellar space was filled
      up with fibrin glue. An additional layer of hemostatic material was added at the
      topography of the preexisting sellar floor, and a second amount of fibrin glue
      was applied over it. At the end of surgery, a continuous lumbar CSF drainage
      system was installed in group 2 patients and kept for 5 days. Prophylactic
      antibiotics were administered during this period. RESULTS: We did not observe
      delayed CSF leak, meningitis, or visual loss in group 1 patients. In group 2, 2
      patients presented with complications: 1 patient got meningitis but no overt CSF
      leak, and the other disclosed a delayed postoperative leak treated by
      reoperation. DISCUSSION: Our results showed that closure of the sellar floor with
      hemostatic material and fibrin glue without grafting or the use of implants is a
      safe and efficient method to prevent postoperative complications after TS.
      Generally speaking, there is no need for grafting or the use of implants at the
      end of TS.

PMID- 16793441
TI  - Retrospective analysis of the surgically treated temporal lobe arteriovenous
      malformations with focus on the visual field defects and epilepsy.
AB  - BACKGROUND: Authors investigate the surgical outcomes of the temporal lobe
      arteriovenous malformation (AVM) with focus on the visual field deficit and
      seizure. METHODS: Between 1981 and 2004, we experienced 294 cases of intracranial
      AVMs. Among the 294 cases, 45 (15.3%) were located in the temporal lobe. Twenty
      six of the 45 cases underwent microsurgical excisions of the AVMs. RESULTS: The
      male-female ratio of 26 surgically treated temporal lobe AVMs was 15:11. The mean
      age was 34.2 years, ranging from 7 to 63 years. The sites of lesion were
      classified as polar in 1, dorsal in 2, laterobasal in 15, and mediobasal in 8.
      The initial symptoms were hemorrhage in 22 and epilepsy in 4 cases. Arteriovenous
      malformations were totally removed in all 26 patients and there was no surgical
      mortality. The visual field deficits were identified in 17 of 22 patients with
      hemorrhage. Massive hematoma cases that needed emergency operation were 5. Visual
      field deficits improved in only 2 of the 5 patients after surgery. Among the 7
      quadrantanopia patients, 3 resulted in hemianopia after surgery. Seven of 22
      hemorrhage patients had history of epilepsy. Although one patient had new
      postoperative epilepsy, the medical controls of the seizure were good in all 8
      patients. Four patients underwent AVM excision for epilepsy without hemorrhage.
      In two patients, seizures disappeared after surgery. The other two patients had
      typical psychomotor seizures after the total excision of AVMs. CONCLUSIONS:
      Improvement of visual field deficit due to hematoma was difficult in most cases.
      Emergency craniotomy for global neurological deterioration due to massive
      hematoma had improved the visual field deficit in two cases. Although the outcome
      of seizure associated with hemorrhage was acceptable, the postoperative
      intractable seizures would remain in cases with epilepsy without hemorrhage.
      Intraoperative electrocorticography might be requisite for nonruptured temporal
      lobe AVM cases with epilepsy.

PMID- 16793443
TI  - Arachnoid cysts in adults: long-term follow-up of patients treated with internal
      shunts to the subdural compartment.
AB  - BACKGROUND: We have previously presented an alternative method for surgical
      decompression of intracranial arachnoid cysts. This minimally invasive method,
      with insertion of an internal shunt from the cyst to the subdural compartment,
      seemed to be an efficient and simple, and hence promising technique. The aim of
      the present study was to investigate the long-term results of this procedure.
      METHODS: This study is a questionnaire-based retrospective study that includes 31
      adult patients (>18 years) who were operated on in our department for an
      arachnoid cyst in the temporal fossa or overlying the frontal convexity with the
      internal shunt technique between April 1990 and October 2003. Follow-up ranged
      from 15 months to 14.8 years (mean = 8.2 years). RESULTS: Of the patients, 83%
      were asymptomatic or had insignificant complaints at follow-up. A total of 17%
      reported no reduction of the preoperative complaints. No patient experienced
      worsening of the symptoms. The cyst was no longer visible on postoperative
      radiologic examinations in 37% of the patients. In 37%, the postoperative fluid
      volume was less than 50% of the original volume. In 13%, the cyst volume was
      reduced but the postoperative volume was greater than 50% of the original cyst
      volume. Thus, the cyst was unchanged in only 13% of the patients. There was no
      correlation between volume reduction and clinical improvement. A complication
      (subdural hygroma or hematoma) occurred in 7 patients, all with temporal cysts,
      leading to reoperation in 4. None of the complications caused permanent
      neurologic deficits or invalidity. Seven patients were reoperated on because of
      suspected or established treatment failure. CONCLUSIONS: The internal shunt
      technique is a relatively simple, safe, and efficient alternative method for
      treatment of arachnoid cysts. It should be considered a valuable alternative in
      the treatment of arachnoid cysts.

PMID- 16793445
TI  - Variations of disseminated choroid plexus papilloma: 2 case reports and a review
      of the literature.
AB  - BACKGROUND: Choroid plexus papillomas are typically considered benign lesions,
      but histology is not always predictive of their behavior. These tumors can
      metastasize anywhere along the neuraxis and may be intraventricular,
      subarachnoid, or intraparenchymal. We present 2 cases that illustrate the wide
      diversity with which choroid plexus papillomas can disseminate. CASE
      DESCRIPTIONS: The patient described in case 1 had a primary fourth ventricular
      choroid plexus papilloma that produced diffuse cystic subarachnoid and
      leptomeningeal lesions. Patient 2 also had a primary fourth ventricular tumor but
      with subsequent suprasellar and spinal drop metastases. Patient 1 was treated
      with temozolomide, resulting in regression of symptoms including headache and
      dizziness. Patient 2 has been treated with several modalities, including
      radiation therapy and chemotherapy, with slowing of symptom progression.
      CONCLUSIONS: Variations of choroid plexus papilloma dissemination include
      intraventricular, subarachnoid, and leptomeningeal nodules or cystic lesions, and
      intraparenchymal locations. There is no consensus on the most effective treatment
      for choroid plexus papilloma metastases; surgical resection, chemotherapy, and
      radiation therapy may all yield benefits. The prognosis for patients with
      disseminated choroid plexus papilloma can range from prolonged stable disease and
      symptoms to death within months.

PMID- 16793447
TI  - Surgery for intramedullary tuberculoma of the spinal cord: report of 2 cases.
AB  - BACKGROUND: Intramedullary tuberculomas are rare. With the widespread
      availability of MRI and the increasing incidence of HIV and HIV-related
      tuberculous infections, the incidence of these lesions is likely to increase
      worldwide. The role of medical and surgical treatment of these relatively rare
      lesions remains to be defined. We report 2 patients who presented with
      intramedullary tuberculomas and discuss the importance of early surgery in this
      condition. CASE DESCRIPTION: Two female patients presented with insidious onset
      of myelopathy. The first patient had seizures due to imaging-documented
      intracranial tuberculomata and progressive paraparesis due to an intramedullary
      tuberculoma. The second patient had also had insidious onset of myelopathy and
      evidence of an intramedullary tuberculoma in MRI. She was also found to have
      abdominal and pulmonary tuberculosis. In view of the presence of tuberculosis
      elsewhere in the body in both the patients and the classical imaging features of
      intramedullary tuberculoma, they were treated initially with antituberculous
      chemotherapy. However, despite chemotherapy, both patients did not show
      improvement. Subsequently, both patients underwent microsurgical removal of the
      intramedullary lesions. The first patient who was neurologically well preserved
      at the time of surgery improved, whereas the second patient who was paraplegic
      with sphincter disturbances did not show any improvement. CONCLUSIONS: These case
      reports are presented to highlight the role of early surgery in patients with
      profound neurological deficits and intramedullary tuberculoma even if the
      radiological appearance of the lesion is characteristic. Even in lesions that are
      potentially curable by chemotherapy, early surgery has an important role in the
      treatment.

PMID- 16793449
TI  - Middle and posterior fossa aspergilloma.
AB  - BACKGROUND: Aspergilloma of the brain is a rare disease. Among its varied
      presentations, a solitary intracranial mass is very uncommon. A preoperative
      diagnosis of it is very difficult, but a perioperative squash smear/frozen
      section can identify the pathology. Because of its rarity in immunocompetent
      patients and the difficulty in preoperative diagnosis, we have illustrated this
      case and its presentation and management. METHODS: A 27-year-old man presented
      with an h/o right-sided weakness along with headache and ear discharge. A
      computed tomographic (CT) scan showed a large irregular, space-occupying lesion
      in the middle and posterior cranial fossa. He had a mastoidectomy done 3 years
      before for chronic suppurative otitis media. After a symptom-free interval of 1
      year, he was investigated for severe earache on the same side. A CT scan at that
      time showed a space occupying mass in the right temporal bone and right inferior
      temporal lobe. A biopsy and histopathology of the lesion revealed a chronic
      granulomatous mass. He was started on antituberculous drugs and was on it for 7
      months at the time of presentation. RESULTS: He underwent a suboccipital
      craniectomy and total excision of the mass. Postoperatively, his consciousness
      improved but began to deteriorate on the third postoperative day. A repeat CT
      scan showed hydrocephalus and total removal of the mass. An external ventricular
      drain was put and he was ventilated, but he died on the fourth postoperative day.
      Histopathology report came as aspergilloma. CONCLUSION: This report highlights
      the rare presentation of aspergilloma in an immunocompetent patient. It
      emphasizes the importance of suspecting this disease in such patients and the
      role of intraoperative squash smear preparations or frozen section in the
      diagnosis as routine diagnostic procedures that will help in early
      pharmacotherapeutic interventions in adjunct to surgery.

PMID- 16793451
TI  - Development of a giant cervical vertebral artery pseudoaneurysm after a traumatic
      C1 fracture: case illustration.

PMID- 16793454
TI  - Traumatic pseudoaneurysm of the superficial temporal artery treated by
      endovascular coil embolization.
AB  - We describe an exceptional case of a traumatic pseudoaneurysm of the superficial
      temporal artery (STA), which was treated with microcoil embolization of the
      anterior branch of the STA. We conclude that endovascular coil embolization can
      be an option of in the treatment of STA pseudoaneurysms.

PMID- 16793452
TI  - Return of vision after transarterial coiling of a carotid cavernous sinus
      fistula: case report.
AB  - BACKGROUND: Carotid cavernous sinus fistulae are abnormal communications between
      the carotid circulation and cavernous sinus that may arise spontaneously or
      develop after craniocerebral trauma. They may present with a constellation of
      signs and symptoms characteristic of raised cavernous sinus pressure, including
      orbital or retro-orbital pain, pulsatile proptosis, chemosis, ocular or cranial
      bruit, deterioration of visual acuity, or ophthalmoplegia. Visual loss is likely
      the result of multiple insults to the visual system, including reversal of venous
      drainage from the fistula, arterial flow into the superior ophthalmic vein,
      increased intraocular venous pressure, venous stasis retinopathy, and eventually
      ischemic optic neuropathy [Brodsky MC, Hoyt WF, Halbach VV, et al. Recovery from
      total monocular blindness after balloon embolization of carotid-cavernous
      fistula. Am J Ophthalmol 1987;104:86-87; Sanders MD, Hoyt WF. Hypoxic ocular
      sequelae of carotid-cavernous fistulae: study of the causes of visual failure
      before and after neurosurgical treatment in a series of 25 cases. Br J Ophthalmol
      1969;53:82-97]. CASE DESCRIPTION: With few exceptions, the literature is replete
      with evidence of persistent blindness despite successful treatment of the CCF
      [Albuquerque FC, Heinz GW, McDougall CG. Reversal of blindness after transvenous
      embolization of a carotid-cavernous fistula: case report. Neurosurgery
      2003;52:233-237; Brodsky MC, Hoyt WF, Halbach VV, et al. Recovery from total
      monocular blindness after balloon embolization of carotid-cavernous fistula. Am J
      Ophthalmol 1987;104:86-87; Weinstein JM, Rufenacht DA, Partington CR, et al.
      Delayed visual loss due to trauma of the internal carotid artery. Arch Neurol.
      1991;48:490-497]. Here, we report a patient who experienced recovery of vision
      after endovascular obliteration of the offending CCF. DISCUSSION: To our
      knowledge, this is the second reported case of recovery of visual function in a
      patient presenting with loss of light perception after treatment of a direct CCF.

PMID- 16793455
TI  - Resection of a giant anterior sacral meningocele via an anterior approach: case
      report and review of literature.
AB  - BACKGROUND: An anterior sacral meningocele is a rare form of spinal dysraphism
      that is sometimes associated with syndromes such as Currarino and Marfan
      syndromes. These lesions rarely cause neurological complications, but meningitis,
      sepsis, obstetric problems, and bowel and bladder difficulties are common
      secondary conditions. The lesions can even be fatal. Because these lesions
      usually do not regress spontaneously, surgical treatment is the standard for
      symptomatic or growing masses. The dural defect can be repaired with a variety of
      anterior or posterior approaches. CASE DESCRIPTION: We present a case of a 16
      year-old female patient with a giant nonsyndromic anterior sacral meningocele
      that we successfully treated using an open anterior approach. We discuss the
      treatment options and present a brief review of the literature. CONCLUSIONS:
      Although the posterior approach remains the treatment of choice for most lesions,
      we believe that the anterior laparotomy provides excellent exposure and is a safe
      alternative approach for the treatment of selected lesions. Patients with these
      lesions should be cared for by a multidisciplinary team.

PMID- 16793457
TI  - Unusual presentations of craniovertebral junction tuberculosis: a report of 2
      cases and literature review.
AB  - BACKGROUND: CVJ tuberculosis is a described entity requiring challenging ways of
      management. Severe neck pain, causing restricted neck movements and torticollis,
      is a characteristic presentation of neurologically asymptomatic suboccipital
      Pott's disease. CASE DESCRIPTION: Two patients with unusual CVJ tuberculosis form
      the basis for the present communication. The first patient presented with
      tubercular otitis media, causing progressive erosion of the petrous part of
      temporal bone, and destruction of the occipital condyle, along with the lateral
      mass of atlas, leading to CVJ instability. This is a first report of such a
      presentation, according to our knowledge. Detailed bony architectural destruction
      demonstrable on CT scan has been described. The second patient, with CVJ
      tuberculosis, presented with skull base syndrome and with multiple cranial nerve
      palsies. Both patients were managed without surgical intervention and showed
      clinical and radiological recovery. CONCLUSION: In such patients with unusual
      clinical presentations, histopathologic examination is necessary to arrive at a
      correct diagnosis. The management of patients with tubercular involvement of CVJ
      remains controversial. In the present communication, both the patients were
      managed successfully with full dose of antitubercular drugs and immobilization.

PMID- 16793460
TI  - Microneurosurgical training model in fresh cadaveric cow brain: a laboratory
      study simulating the approach to the circle of Willis.
AB  - BACKGROUND: Residents of neurosurgery need many years to develop
      microneurosurgical skills, and laboratory training models are essential for
      developing and refining surgical skills before clinical application of
      microneurosurgery. A simple simulation model is needed for young residents to
      learn how to handle microneurosurgical instruments, and to perform safe
      dissection of intracranial vessels and nerves. METHODS: The material consists of
      a 2-year-old fresh cadaveric cow cranium. A 4-step approach was designed to
      dissect the internal carotid artery and its proximal branches, the optic nerve,
      the optic chiasm, and the pituitary stalk. RESULTS: The model simulates standard
      microneurosurgery using a variety of approaches to vessels and neural structures
      in and around the circle of Willis of the human brain. CONCLUSION: The cadaveric
      cow brain, besides being cost-effective, represents a fairly useful method to
      accustom residents of neurosurgery, especially junior residents, to dissecting
      intracranial vessels and nerves, and it simulates intracranial microneurosurgical
      procedures performed in the human brain.

PMID- 16793463
TI  - Trust, malpractice, and honesty in medicine: should doctors say they are sorry?

PMID- 16793465
TI  - Re: Magnesium sulfate: role as possible attenuating factor in vasospasm morbidity
      (Prevedello DM et al. Surg Neurol 2006;65:S1:14-S1:21).

PMID- 16793466
TI  - Modern endodontic surgery concepts and practice: a review.
AB  - Endodontic surgery has now evolved into endodontic microsurgery. By using state
      of-the-art equipment, instruments and materials that match biological concepts
      with clinical practice, we believe that microsurgical approaches produce
      predictable outcomes in the healing of lesions of endodontic origin. In this
      review we attempted to provide the most current concepts, techniques, instruments
      and materials with the aim of demonstrating how far we have come. Our ultimate
      goal is to assertively teach the future generation of graduate students and also
      train our colleagues to incorporate these techniques and concepts into everyday
      practice.

PMID- 16793467
TI  - A comparison between in vivo radiographic working length determination and
      measurement after extraction.
AB  - The purpose of this study was to compare the difference between the in vivo
      working length established by viewing a periapical radiograph and the in vitro
      measurement from the file tip to the apical foramen of the extracted tooth.
      Twenty-six canals from teeth that had been treatment planned for extraction were
      accessed under rubber dam isolation. The coronal portion of each canal was flared
      using Gates Glidden drills, and a K-type file was inserted down the canal until
      an electronic apex locator indicated that the file had reached the apex. A size
      20 K-type file was locked into place with glass ionomer cement at this position.
      A radiograph was exposed and the tooth was extracted. Each tooth was viewed using
      a videomicroscope at 30x original magnification, and the distance from the file
      tip to the most coronal aspect of the major foramen was measured. Six examiners
      viewed each radiograph and assessed the working length of each canal. Chi(2)
      analysis of the data revealed a significant difference (p < 0.01) between the
      estimation of working lengths and the microscopic measurements. The examiners
      overestimated the distance between the file tip and the apical foramen of the
      tooth when the file was placed short, and underestimated the distance when the
      file was placed long. In conclusion, when the file is short it is actually closer
      to the apical foramen than it appears radiographically; when it is long it is
      actually longer than it appears radiographically.

PMID- 16793468
TI  - Healing of apical periodontitis after endodontic treatment with and without
      obturation in dogs.
AB  - The principle of obturation of the root canal space is generally accepted. This
      belief has dominated the field of endodontics despite the absence of credible
      scientific evidence. Little information is available on the possible
      relationships between endodontic success and obturation of the root canal system.
      The present study compares the healing of instrumented and obturated versus
      instrumented and nonobturated root canal systems with apical periodontitis. Fifty
      six root canals in 28 third and fourth bilateral lower premolar teeth with
      completely formed apices in seven mixed German Shepherd dogs were used. Apical
      lesions were created by accessing the canals, removing the pulp and leaving them
      open to the oral environment for 42 days. The teeth in the control group were
      instrumented, irrigated, and then obturated using a lateral condensation
      technique with gutta-percha cones and AH26 Plus as the endodontic sealer. The
      teeth in the experimental group were instrumented and irrigated without
      obturation. All teeth in both groups were sealed coronally. After 190 days, the
      animals were euthanized. Vital perfusion with 10% formalin through common carotid
      artery was performed. Thirty to 40 serial 5-microm thick sections were obtained
      from each root and stained with hematoxylin and eosin for histological evaluation
      by observer blinded to the treatment allocation. The control group showed less
      cementum and dentin resorption in comparison with test group (p < 0.5). No
      statistically significant difference was found in other parameters between the
      control and test groups (p > 0.05). The noteworthy finding of this study was that
      there was no difference in healing of apical periodontitis between the
      instrumented and obturated and instrumented and nonobturated root canal system.
      The success of endodontic treatment ultimately depends on the elimination of the
      microorganism, host response and mechanical closure (coronal seal) of treated
      root canals that may provide a potential for future bacterial contamination.

PMID- 16793469
TI  - Enterococcus faecalis adhesin, Ace, mediates attachment to particulate dentin.
AB  - An enzyme linked immunosorbent assay was developed to assess E. faecalis adhesion
      to particulate dentin. E. faecalis, OG1RF, which expresses the collagen binding
      protein (Ace+), and a derivative of OG1RF, TX5256, deficient in the collagen
      binding protein (Ace-) were grown at 46 degrees C, necessary for in vitro
      expression of Ace, and at 37 degrees C. E. faecalis binding to dentin was
      measured at 0, 15, 30, 60, 120, and 360 minutes. Compared to TX5256 and OG1RF
      grown at 37 degrees C, OG1RF grown at 46 degrees C adhered significantly better
      at all time points except 15 minutes (p < 0.001) exhibiting maximum binding at
      120 minutes (17.4% of a positive control). Type I collagen at 100 microg/ml
      inhibited dentin binding by OG1RF grown at 46 degrees C in both competition (p <
      0.005) and displacement assays (p < 0.046). Immunoaffinity purified anti-Ace IgG
      at 200 microg of protein inhibited adhesion of OG1RF grown at 46 degrees C to
      dentin.

PMID- 16793470
TI  - Denaturation temperatures of dentin matrices. I. Effect of demineralization and
      dehydration.
AB  - The denaturation temperature (T(d)) of dentin collagen in mineralized versus
      demineralized teeth was examined as a function of dentin age and the extent of
      dehydration. Using differential scanning calorimetry, T(d) of mineralized dentin
      was shown to be between 160 degrees C to 186 degrees C, depending on whether it
      was from young or old dentin that was hydrated or dehydrated, respectively.
      Demineralized dentin exhibited a T(d) of 65.6 degrees C that increased with
      dehydration to 176 degrees C. The presence of apatite crystallites or
      interpeptide bonding increased the T(d) of demineralized matrices. Interpeptide
      hydrogen bonding seems to stabilize collagen to thermal challenge. Water breaks
      interpeptide hydrogen bonds making collagen more susceptible to thermal
      denaturation. Rises in intracanal temperature are unlikely to cause extensive
      denaturation of mineralized root dentin walls. However, hydrated or partially
      dehydrated root canal walls that have been partially demineralized with chelating
      agents or mild acids may be susceptible to thermal denaturation.

PMID- 16793471
TI  - A fluid filtration comparison of gutta-percha versus Resilon, a new soft resin
      endodontic obturation system.
AB  - The purpose of this study was to compare the sealing ability of gutta-percha and
      AH Plus sealer versus Resilon and Epiphany Resin Root Canal sealer using three
      different final irrigants with the fluid filtration model. There were 140 teeth
      prepared using a crown-down method to a size 50 file. The teeth were randomly
      divided into two groups: (A) GP and AH Plus and (B) Resilon and Epiphany. After
      removal of the smear layer each group was irrigated with either 5.25% NaOCl,
      0.012% chlorhexidine (CHX), or 2% CHX for 10 minutes. Obturation was performed
      using the continuous wave of condensation. The teeth were stored for 20 days in
      100% humidity before testing. Two-way ANOVA analysis indicated significantly less
      leakage (p < 0.05) using Resilon with Epiphany sealer compared to gutta-percha
      and AH Plus sealer. There was no statistical significance between any of the
      irrigants used for either obturation group.

PMID- 16793472
TI  - Bacterial count comparisons on examination gloves from freshly opened boxes
      versus nearly empty boxes and from examination gloves before treatment versus
      after dental dam isolation.
AB  - Use of gloves in dentistry is primarily for protection of the healthcare worker,
      yet little information is available regarding potential patient issues such as
      microbial contamination of gloves before and during use. The purposes of this
      study were to compare gloves from newly opened boxes with those from boxes that
      had been in dental operatories until they were nearly empty and to determine if
      gloves are contaminated though diagnostic procedures and rubber dam placement.
      Eight endodontic residents provided samples by streaking gloved fingers on
      nutrient agar plates. Results showed no statistically significant difference
      between counts from new boxes versus nearly empty boxes (n = 32, p < 0.6216).
      Gloves after rubber dam placement yielded a mean colony count of 158 versus a 1.5
      mean of fresh gloves (n = 64, p < 0.0001). These results suggest that the use of
      new gloves before opening a tooth for endodontic therapy may be warranted.

PMID- 16793473
TI  - Microbial contamination of endodontic files received from the manufacturer.
AB  - This study was conducted to test the sterility of new unused endodontic files
      received from manufacturers. Fifteen types of hand and rotary files from five
      manufacturers were tested. Positive microbial cultures were obtained from 13% of
      the 150 files tested. Autoclaved files were intentionally contaminated with
      bacterial species recovered from the positive cultures to evaluate a chairside
      sterilization method. Immersion of contaminated files in 5.25% sodium
      hypochlorite for five minutes sterilized the files. The results of this study
      indicate that endodontic files should be sterilized before clinical use. It is
      also suggested that manufacturers list the sterility state of their endodontic
      files on their packaging.

PMID- 16793474
TI  - A comparison of the antimicrobial efficacy of NaOCl/Biopure MTAD versus
      NaOCl/EDTA against Enterococcus faecalis.
AB  - The purpose of this investigation was to compare the antimicrobial efficacy of
      irrigating with 1.3% NaOCl/Biopure MTAD versus irrigation with 5.25% NaOCl/15%
      EDTA in the apical 5 mm of roots infected with Enterococcus faecalis. Bilaterally
      matched human teeth were sterilized and inoculated with E. faecalis. After
      chemomechanical root canal preparation, the root-ends were resected and
      pulverized in liquid nitrogen to expose E. faecalis in dentinal tubules or other
      recesses away from the main root canal system. The number of colony forming units
      (CFU) of E. faecalis per mg was determined from the pulverized root-ends. No
      significant differences were seen (t = 0.70, p = 0.495) between the number of
      colony forming units of E. faecalis for teeth irrigated with 5.25% NaOCl/15% EDTA
      (mean 131 +/- 291 CFU/mg) versus those teeth irrigated with 1.3% NaOCl/Biopure
      MTAD (mean 187 +/- 237 CFU/mg). This study demonstrated that there is no
      difference in antimicrobial efficacy for irrigation with 5.25% NaOCl/15% EDTA
      versus irrigation with 1.3% NaOCl/Biopure MTAD in the apical 5 mm of roots
      infected with E. faecalis.

PMID- 16793475
TI  - Comparison of the intraosseous biocompatibility of AH Plus, EndoREZ, and Epiphany
      root canal sealers.
AB  - To evaluate the intraosseous biocompatibility of AH Plus, EndoREZ, and Epiphany
      root canal sealers as recommended by the Technical Report #9 of the Federation
      Dentaire Internationale (FDI). Thirty guinea pigs, 10 for each material, divided
      into experimental periods of 4 and 12 weeks, received one implant on each side of
      the lower jaw symphysis. At the end of the observation periods, the animals were
      killed and the specimens prepared for routine histological examination. After
      analyzing both periods, the inflammatory tissue reaction to EndoREZ was
      considered severe. In the AH Plus group, the reaction changed from severe to
      moderate, while it was observed biological compatibility to Epiphany with bone
      formation and none to slight inflammatory reaction. It was concluded that
      Epiphany root canal sealer was the only material that presented intraosseous
      biocompatibility within the two analyzed periods.

PMID- 16793476
TI  - Effect of smear layer and chlorhexidine treatment on the adhesion of Enterococcus
      faecalis to bovine dentin.
AB  - The aim of this in vitro study was to determine the effects of a smear layer and
      chlorhexidine (CHX) treatment on the adhesion of Enterococcus faecalis to bovine
      dentin. Forty dentin blocks from bovine incisors were prepared and randomly
      divided into four groups of 10 each. The blocks in group 1 were placed in sterile
      saline for 5 minutes, while those in group 2 were treated with 17% EDTA for 5
      minutes. The blocks in group 3 were placed in 2% CHX for 7 days. The blocks in
      group 4 were treated with 17% EDTA for 5 minutes, and then placed in 2% CHX for 7
      days. All the blocks were immersed in a suspension of E. faecalis for 3 hours.
      The bacteria adhering to the dentin surface were counted by examination using a
      scanning electron microscope. The most significant amount of bacteria was
      retained on the samples from group 1 (p < 0.05) and the smallest amount of
      bacteria adhered to the samples from group 4. These results suggest that a smear
      layer enhances the adherence of E. faecalis to the dentin, and CHX is effective
      in reducing the adherence of microorganisms.

PMID- 16793477
TI  - Comparative evaluation of three nickel-titanium instrumentation systems in human
      teeth using computed tomography.
AB  - This study investigated several parameters of root canal preparation with three
      different rotary NiTi systems: Hero Shaper, ProTaper, and RaCe. The parameters
      evaluated were: changes in root canal volume and cross-sectional area, canal
      transportation, and working time. Curved, mesial molar roots were scanned in a
      computed tomography (CT) unit before and after instrumentation. Cross-sectional
      views of each canal were obtained at 1 mm intervals. Postinstrumentation volume
      and cross-sectional area of root canals and the extent of transportation were
      calculated using image analysis software and, thereafter, subjected to
      statistical analysis. ProTaper removed significantly more dentin than Hero Shaper
      (p < 0.05). Instrumentation increased the cross-sectional area at all cutplanes,
      while the difference between test groups was not significant (p > 0.05). RaCe
      files significantly transported the canals at the coronal level (p < 0.05). There
      was no difference between any rotary systems in regards to working time.

PMID- 16793478
TI  - In vitro assessment of a gel base containing 2% chlorhexidine as a sodium
      perborate's vehicle for intracoronal bleaching of discolored teeth.
AB  - The purpose of this study was to assess a gel base containing 2% chlorhexidine
      (CHX) as a vehicle to be mixed with sodium perborate for intracoronal bleaching
      of discolored teeth, comparing its bleaching efficacy to sodium perborate mixed
      with other vehicles; 37% carbamide peroxide and 30% hydrogen peroxide. There were
      110 fresh bovine incisors artificially stained using whole blood. The samples
      were divided into 11 groups and the intracoronal bleaching was performed using
      the "walking bleach technique". The bleaching agents were replaced three times at
      7-day intervals. Using digital photos and a shade guide created for bovine teeth,
      the samples were evaluated at day 0, 7, 14, 21, and 28. On evaluation day, the
      photos were examined by three endodontists giving scores from 1 to 5 based on the
      shade guide created. Data were analyzed statistically by Kruskall-Wallis test.
      After 28 days, all evaluated teeth received scores that were statistically
      similar. Groups that used sodium perborate and a liquid vehicle bleached faster
      than those that used a gel based vehicle. The CHX gel allowed dissociation for
      the bleaching agent. The 2% CHX gel exhibited a good potential for use as a
      vehicle for sodium perborate or as a complement for carbamide peroxide.

PMID- 16793479
TI  - SEM observations and differential scanning calorimetric studies of new and
      sterilized nickel-titanium rotary endodontic instruments.
AB  - Scanning electron microscopy (SEM) and differential scanning calorimetric (DSC)
      studies were utilized to investigate surface and microstructure of two brands of
      rotary nickel-titanium (NiTi) endodontic instruments, in the as-received
      condition and after subjection to 1, 6, and 11 sterilization cycles. A total of
      66 ProFile (n = 33) and Flexmaster (n = 33) files were examined. SEM observations
      indicated the presence of surface imperfections and adherent material in all new
      and sterilized instruments and an increase in surface roughness of the
      instruments that underwent multiple sterilizations. DSC measurements showed that
      the specimens of both brands, in the as-received condition and after 11
      sterilizations, were completely austenite in the oral environment temperature,
      suggesting that they are capable of superelastic behavior in appropriate clinical
      conditions.

PMID- 16793480
TI  - Delivery of calcium hydroxide: comparison of four filling techniques.
AB  - This study compared the weight and radiographic appearance of Ca(OH)(2) delivered
      into standardized, minimally and fully prepared canals using (a) an injection
      system, (b) an endodontic Flex-O file rotated counter-clockwise, (c) a lentulo
      spiral, and (d) a .04 rotary NiTi file rotated in reverse. Two extracted human
      second mandibular premolars with single canals were prepared to an MAF #25 or an
      MAF #40. A weight measurement and radiograph were made for each filling. Three
      independent examiners evaluated the radiographs. Regardless of technique, only
      about 45% of the optimal weight of Ca(OH)(2) was delivered into the minimally
      prepared canal. Radiographically the filling quality was only 1 to 2 (10 scale).
      In contrast, all delivery techniques delivered near optimal weight of Ca(OH)(2)
      in the completely prepared canal with a radiographic filling quality of 8.8 to
      9.3. The results indicate that complete instrumentation is needed to obtain near
      optimal delivery of Ca(OH)(2).

PMID- 16793481
TI  - A comparison of thermal properties between gutta-percha and a synthetic polymer
      based root canal filling material (Resilon).
AB  - A new polymer-based obturating material, Resilon, has been developed but there
      have been no studies identifying its thermal properties. The purpose of this
      study was to compare the melting point, specific heat, enthalpy change with
      melting and heat transfer between gutta-percha (GP) and Resilon (R). The first
      three tests were determined using a differential scanning calorimeter and the
      heat transfer test was determined using a split-tooth model. Results show no
      significant difference (t test, p > 0.05) between gutta-percha and Resilon for
      the melting point temperature (GP: 60.01 degrees C; R: 60.57 degrees C). There
      was a significant difference (t test, p < 0.05) in specific heat capacity (GP:
      0.94 J/g degrees C, R: 1.15 J/g degrees C) and endothermic enthalpy change (GP:
      10.88 J/g, R: 25.20 J/g) between the two materials. The heat transfer test showed
      a significant difference (Mann-Whitney, p < 0.05) in temperature increase between
      gutta-percha and Resilon within 3 mm of the heat source.

PMID- 16793482
TI  - Endodontic management of a maxillary first molar with a single root and a single
      canal diagnosed with the aid of spiral CT: a case report.
AB  - The aim of this article is to present an endodontically managed maxillary first
      molar with an unusual morphology of a single root and a single canal, which has
      not been reported in the literature so far. An accurate assessment of this
      unusual morphology was made with the help of a Spiral computed tomography. This
      report extends the range of known possible anatomical variations to include teeth
      with lesser number of roots and canals. This report also highlights the role of
      Spiral computed tomography as an objective method to confirm the three
      dimensional anatomy of teeth.

PMID- 16793483
TI  - Aspergillus mycetoma of the maxillary sinus secondary to overfilling of a root
      canal.
AB  - In nonimmunocompromised patients aspergillosis of the paranasal sinuses is a
      relatively rare disease. Root canal treated teeth with overextension of the root
      canal sealer or solid materials such as gutta-percha or silver cones into the
      sinus might be the main etiological factor for aspergillosis of the maxillary
      sinus in healthy patients. Root-filling materials based zinc oxide-eugenol is
      considered to be a growth factor for aspergillus. Aspergillus fumigatus needs
      heavy metals such as zinc oxide for proliferation and metabolism. Prognostic and
      histological studies showed that instrumentation and obturation should not extend
      beyond the apical foramen. When the sealer and/or gutta-percha is extruded within
      the sinus, this produce an inflammatory reaction and then Aspergillus growth. We
      report one case of healthy 60-yr-old male with overextension of root canal sealer
      in maxillary sinus. After surgical procedure, microscopic examination revealed
      aspergillosis. Overextension into the maxillary sinus with root canal cements has
      to be avoided.

PMID- 16793485
TI  - The Lake Bluff Forum for academic palliative medicine.

PMID- 16793484
TI  - Effect of bacteriocin produced by Lactococcus sp. HY 449 on skin-inflammatory
      bacteria.
AB  - This study was carried out to evaluate the effect of bacteriocin produced by
      Lactococcus sp. HY 449 against skin-inflammatory bacteria such as Staphylococcus
      epidermidis ATCC 12228, Staphylococcus aureus ATCC 65389, Streptococcus pyogenes
      ATCC 21059, and Propionibacterium acnes ATCC 6919. The spot-on-the-lawn method
      was used to determine the antimicrobial activity of bacteriocin against indicator
      strains on the human skin. The bacteriocin produced by Lactococcus sp. HY 449
      inhibited the growth of S. epidermidis ATCC 12228, S. aureus ATCC 65389, Strep.
      pyogenes ATCC 21059, and P. acnes ATCC 6919. The treatment of crude bacteriocin
      caused a rapid inactivation of P. acnes ATCC 6919. The LC50 of bacteriocin on
      human fibroblast was ca. 50mg/ml at which the inhibition of cell proliferation
      was not observed. Neither any irritations nor allergic reactions by the
      bacteriocin were evident in a human patch test. The bacteriocin produced by
      Lactococcus sp. HY 449 may be a useful antimicrobial substance to control the
      growth of P. acnes and to prevent skin inflammation and acne.

PMID- 16793486
TI  - Complex regional pain syndrome type I as a complication of axillary clearance.

PMID- 16793487
TI  - Collaboration in difficult pain control in palliative medicine--it's good to
      talk.

PMID- 16793488
TI  - Palliative performance status, heart rate and respiratory rate as predictive
      factors of survival time in terminally ill cancer patients.
AB  - To determine which symptoms, signs, and characteristics that define the patient's
      functional status predict the survival time in terminally ill cancer patients, a
      prospective longitudinal study was conducted with terminally ill cancer patients
      followed by a Home Care Support Team. Patients were followed up with at least
      weekly visits until death, collecting variables at each visit. A Cox multivariate
      regression analysis took into account all the follow-ups in the same patient.
      Ninety-eight patients were studied, and 250 evaluations were done. The mean age
      was 72 years. The median survival was 32 days. In the multivariate analysis,
      three independent variables were identified: Palliative Performance Score of 50
      or under, heart rate of 100/minute or more, and respiratory rate of 24/minute or
      more. The variables that were found to be prognostic in our study are objective,
      easy, and quick to measure, and do not require that the professional have special
      training or experience. The prediction of survival time may be improved by
      considering these variables.

PMID- 16793489
TI  - Uric acid as a prognostic factor for survival time: a prospective cohort study of
      terminally ill cancer patients.
AB  - The aim of this prospective cohort study was to determine whether serum uric acid
      level is useful as a predictor of survival in terminally ill cancer patients. One
      hundred eighteen terminally ill cancer patients, including 63 (53.4%) males, were
      categorized into four groups by serum uric acid levels and followed up until
      death or to the end of the study. Cox's proportional hazard model was adopted to
      evaluate the joint effect of some clinicobiological variables on survival. From
      an initial model containing 51 variables, a final parsimonious model was obtained
      by means of a stepwise method. Repetitive dispersion analysis was performed for
      serum uric acid level in 39 subjects for 3 weeks until death. During the study
      period, 113 (95.76%) subjects expired, and the median survival time was 14 days.
      In univariate analysis, survival time of the fourth highest group (> or
      =7.2mg/dL) was significantly shorter than that of the others (hazard ratio
      (HR)=2.784, P<0.001). After adjustment for low performance status, moderate to
      severe pain, prolonged prothrombin time, hypocholesterolemia, and high lactate
      dehydrogenase (LDH) level, high serum uric acid level (> or =7.2mg/dL) was
      significantly and independently associated with short survival time (HR=2.637,
      P=0.001). Serum uric acid levels were also significantly increased between the
      first and the second week before death. These findings suggest that serum uric
      acid level can be useful in predicting life expectancy in terminally ill cancer
      patients.

PMID- 16793490
TI  - Protocol for the treatment of malignant inoperable bowel obstruction: a
      prospective study of 80 cases at Grenoble University Hospital Center.
AB  - A prospective protocol for treatment of malignant inoperable bowel obstruction
      was implemented at Grenoble University Hospital Center for 4 years. All 80
      episodes of obstruction resulted from peritoneal carcinomatosis and none could
      expect another treatment cure. The protocol comprised three successive stages.
      Stage I included treatment for 5 days with a corticosteroid, antiemetic,
      anticholinergic, and analgesic. Stage II provided a somatostatin analogue if
      vomiting persisted. After 3 days, Stage III provided a venting gastrostomy.
      Obstruction relief with symptom control was obtained by medical treatment in 29
      cases and symptom control occurred alone in an additional 32 cases. Ten patients
      were relieved by venting gastrostomy. Symptom control without permanent
      nasogastric tube (NGT) placement occurred in 72 episodes (90%). Eight patients
      with refractory vomiting were obliged to continue the NGT until death. Fifty
      eight obstruction episodes (73%) were controlled in 10 days or less. Median time
      before gastrostomy was 17 days. Median survival was 31 days. This series suggests
      that a staged protocol for the treatment of inoperable malignant bowel
      obstruction is highly effective in relieving symptoms. A subgroup experiences
      relief of obstruction using this approach.

PMID- 16793491
TI  - Understanding disparities in aggressive care preferences between patients with
      terminal illness and their family members.
AB  - We examined the factors associated with the disparity in aggressive care
      preferences between patients with terminal cancer and their family members. Two
      hundred forty-four consecutive pairs recruited from three university hospitals
      participated in this study. Each pair completed questionnaires that measured two
      major aggressive care preferences-admission to the intensive care unit (ICU) and
      the use of cardiopulmonary resuscitation (CPR). Sixty-eight percent of patients
      and their family members were in agreement regarding admission to the ICU and 71%
      agreed regarding CPR. Regarding admission to the ICU, younger, unmarried patients
      and patients who preferred to die in an institution were more likely to have a
      different preference from their family caregivers. Regarding CPR, younger
      patients and patients from severely dysfunctional families were more likely to
      have a different preference from their family caregivers. Elucidation of the
      factors associated with such disparities should help reduce them.

PMID- 16793492
TI  - Resource consumption and costs of palliative care services in Spain: a
      multicenter prospective study.
AB  - Patients (n=395) with terminal-stage cancer receiving attention from palliative
      care services (PCSs) were recruited over a period of 15 consecutive days from 171
      participating PCS units. Resource consumption and costs were evaluated for 16
      weeks of follow-up, and the findings were compared with a study conducted in 1992
      so as to assess change over time. The most frequent health care interventions
      were homecare visits, hospital admissions, and patient-consultant phone calls.
      PCS provided 67% of all services and consultation interventions in 91% of
      patients. Compared with the historical data, there was a significant shift from
      the use of conventional hospital beds toward palliative care beds, a reduced
      hospital stay (25.5-19.2 days; P=0.002), an increase in the death-at-home option
      (31%-42%), a lower use of hospital emergency rooms (52%-30.6%; P=0.001), and an
      increase in programmed care. Compared to the previous resource consumption and
      expenditure study in 1992, the current PCS policy implies a cost saving of 61%,
      with greater efficiency and no compromise of patient care.

PMID- 16793493
TI  - Multidimensional measurement of fatigue in advanced cancer patients in palliative
      care: an application of the multidimensional fatigue inventory.
AB  - To investigate the level, dimensionality, and correlates associated with fatigue
      in patients receiving specialist palliative care, 278 advanced cancer patients
      referred to a department of palliative medicine during a 2-year period were asked
      to complete the Multidimensional Fatigue Inventory (MFI-20), a self-assessment
      questionnaire measuring five dimensions of fatigue, and the Hospital Anxiety and
      Depression Scale. Of 267 eligible patients, 130 (49%) participated. Mean fatigue
      scores (0-100 scale) were very high, especially for general fatigue (81),
      physical fatigue (87), and reduced activity (85). Only some of the MFI-20
      subscales were significantly correlated. Fatigue was not correlated with
      sociodemographic factors. Depressed patients had higher scores on all five
      subscales except physical fatigue. Anxious patients had higher levels on the
      mental fatigue subscale only. The variation in fatigue explained by depression
      varied markedly (4%-31%) among subscales. Fatigue levels were very high in this
      population. The lack of significant correlation between some subscales indicates
      that they measure different aspects of fatigue. This is also supported by the
      differences in associations between fatigue subscales and depression and anxiety.

PMID- 16793494
TI  - Filipino version of the M. D. Anderson Symptom Inventory: validation and
      multisymptom measurement in cancer patients.
AB  - Assessing cancer-related symptoms requires a brief, reliable, valid, and
      culturally adapted symptom screening tool. In the Philippines, cancer patients
      (n=206) and community-dwelling adults (n=170) participated in a cross-sectional
      validation study of the Filipino version of the M. D. Anderson Symptom Inventory
      (MDASI-F). Both exploratory factor analysis and hierarchical cluster analysis
      revealed two underlying symptom severity constructs--general and gastrointestinal
      symptoms--consistent with the English, Japanese, and Chinese versions of the
      MDASI. Cronbach alpha coefficients of 0.79 and 0.77, respectively, demonstrated
      acceptable internal consistency for the two factors. Known-group validity was
      confirmed by significant differences on MDASI-F items by performance status
      (P<0.01 or P<0.001). Fatigue, sadness, distress, and pain were significant
      predictors of symptom interference. Cancer patients reported significantly
      greater symptom severity on multiple items than did the community sample. The
      MDASI-F is reliable and valid for evaluating cancer-related symptoms and their
      impact on Filipino cancer patients.

PMID- 16793495
TI  - Change in patients' satisfaction with pain control after using the Korean cancer
      pain assessment tool in Korea.
AB  - Appropriate pain assessment is very important for managing cancer pain. This
      study was designed to evaluate the utility of the Korean Cancer Pain Assessment
      Tool (KCPAT) by assessing changes in the management of cancer pain. The changes
      in pain intensity, the pattern of drug prescriptions, and the patients'
      satisfaction with pain control were analyzed after using the KCPAT. The results
      indicated that pain medicine prescriptions were changed in 194 (51.5%) cases
      after using the KCPAT, and 69.5% of these changes were affected by the KCPAT.
      After using the KCPAT, pain intensity as assessed by the Visual Analogue Scale
      (VAS, 0-10cm) decreased (4.31+/-2.35 vs. 3.60+/-2.45, P<0.0001), and the presence
      of associated symptoms and psychosocial items was significantly reduced. The
      patients' satisfaction with pain control was improved. Forty-four physicians
      (89.8%) thought that the KCPAT was useful. The KCPAT improved patients'
      satisfaction with pain control and was a useful tool for evaluating and managing
      cancer pain.

PMID- 16793496
TI  - Effect of tubing on loss of clonazepam administered by continuous subcutaneous
      infusion.
AB  - Previous studies have reported loss of clonazepam from solutions administered
      intravenously from plastic infusion bags and administration sets. In palliative
      care, clonazepam is sometimes administered through syringe drivers using
      polyvinyl chloride (PVC) infusion tubing. No data currently exist to show whether
      use of PVC tubing affects the amount of clonazepam actually received by the
      patient. This study compared the use of two different types of PVC tubing with a
      non-PVC tubing. Solutions containing clonazepam or clonazepam and morphine were
      prepared with either normal saline or water for injection as diluent.
      Concentrations of morphine and clonazepam were determined using high-performance
      liquid chromatography. Significant loss of clonazepam (up to 50%) was observed in
      all solutions infused through PVC tubing. Solutions infused through non-PVC
      tubing retained greater than 90% of the initial concentration of clonazepam. It
      is recommended that when administering clonazepam using a syringe driver, non-PVC
      tubing be used.

PMID- 16793497
TI  - Intrathecal catheters with subcutaneous port systems in patients with severe
      cancer-related pain managed out of hospital: the risk of infection.
AB  - Intrathecal catheters have been used for many years to treat severe pain
      resistant to conventional treatment modalities. Previous studies have found a
      rate of serious infection of 2%-3% using these catheters in home situations.
      However, many authors used prophylactic antibiotics routinely in this group of
      patients, which are both costly and associated with a risk of developing
      antibiotic resistance. We were interested in studying whether improved hygiene
      during insertion and care of these catheters in the hospice or home environment
      would reduce the incidence of catheter-related infections. The results show that
      prophylactic antibiotic is not necessary, but a careful handling of the system
      with aseptic technique is important. The infections we registered appeared more
      than 2 weeks after insertion of the catheters. We now use this method routinely
      when inserting an intrathecal catheter with a subcutaneous port.

PMID- 16793500
TI  - Basic principles of radiobiology applied to radiotherapy of benign intracranial
      tumors.
AB  - The use of ionizing radiation in the treatment of benign intracranial tumors may
      involve one of several types of ionizing radiation given as single-fraction
      radiosurgery or fractionated radiotherapy. An understanding of the biophysical
      and radiobiologic principles involved in these treatments is essential to the
      design and delivery of safe and efficacious treatment. This article discusses the
      basic radiobiologic principles applicable to radiotherapy of benign brain tumors.

PMID- 16793501
TI  - Single-fraction stereotactic radiosurgery for intracranial targets.
AB  - Stereotactic radiosurgery (SRS) is a technique for treating intracranial lesions
      with a high dose of ionizing radiation, usually in a single session, using a
      stereotactic apparatus for accurate localization and patient immobilization. This
      article describes several modalities of SRS and some of its applications,
      particularly for intracranial lesions.

PMID- 16793502
TI  - Fractionated radiotherapy techniques.
AB  - A convergence of advances in patient immobilization and localization, patient
      imaging, beam shaping and delivery, and treatment planning has led to
      considerable improvement in the ability to deliver highly conformal radiation
      treatments by radiosurgical or fractionated radiotherapy techniques. The
      selection of the "best" treatment technique for any given patient needs to
      consider the morphology of the target and regional organs at risk as well as
      available technology and institutional expertise.

PMID- 16793503
TI  - Meningioma.
AB  - Total excision is an appropriate treatment option for patients with benign
      meningiomas that are resectable with minimal morbidity. It is particularly
      appropriate for patients with significant mass effect causing symptoms.
      Fractionated conformal radiotherapy is an appropriate primary treatment option
      for patients with benign meningiomas of all sizes and all sites. It is
      particularly appropriate and preferred for optic nerve sheath meningiomas, for
      which there are few alternatives. Planned subtotal resection is appropriate if
      decompression is expected to relieve acute symptoms. After subtotal resection, it
      is appropriate to offer single-fraction radiosurgery or multifraction
      radiotherapy, depending on the size, location, and extent of residual tumor, so
      as to achieve progression-free survival and cause-specific survival rates
      comparable to those of other approaches.

PMID- 16793504
TI  - Clinical results: Radiosurgery and radiotherapy of cranial nerve schwannomas.
AB  - Stereotactic radiosurgery and fractionated radiotherapy are two attractive low
      morbidity alternatives to surgical resection for managing cranial nerve
      schwannomas. Treatment outcomes from these radiation treatment approaches are
      well documented with long-term outcome studies from multiple institutions.
      Differences in outcome between these two modalities are difficult to define
      clearly. The low morbidity and high long-term tumor control rates with radiation
      treatment have made it the choice of many patients who opt for active initial
      management for small- or medium-sized cranial nerve schwannomas.

PMID- 16793505
TI  - Clinical results of conformal radiotherapy and radiosurgery for pituitary
      adenoma.
AB  - Radiation therapy provides a valuable adjunct to surgery as well as a viable
      management alternative to surgery for pituitary adenomas. The availability of
      conformal radiotherapy has dramatically reduced complication rates, and the
      advent of radiosurgery has reduced the latency of response in these patients.
      Although extended follow-up is needed to elucidate the long-term outcomes of
      these treatments, they are likely to be a permanent part of the therapeutic
      armamentarium for these patients for the near future.

PMID- 16793506
TI  - Role of radiation therapy and radiosurgery in the management of
      craniopharyngiomas.
AB  - The variable clinical presentation, relation to vital anatomic structures, and
      complications associated with treatment contribute to the controversies that
      surround the management of craniopharyngiomas. Although the results with
      radiation therapy and radiosurgery have been equal to or better than those
      obtained with aggressive surgery, considerable debate exists regarding the role
      of surgery alone versus limited surgery followed by radiation therapy. Based on
      current data, one may consider using surgery for discrete tumors that do not
      involve the hypothalamus and for which gross total resection would result in
      minimal cognitive side effects. For tumors that clearly involve the hypothalamus
      and associated suprasellar structures, subtotal resection followed by radiation
      therapy tailored for the residual disease seems to offer the best long-term
      control rates with acceptable morbidity.

PMID- 16793507
TI  - Less common indications for stereotactic radiosurgery or fractionated
      radiotherapy for patients with benign brain tumors.
AB  - Microsurgical resection remains the mainstay of treatment for truly benign brain
      tumors that can be safely resected because of the potential for permanent cure
      with most histologic findings, including most of the histologic findings
      discussed in this article. Physicians must keep in mind the indolent nature of
      many of the benign brain tumors and realize that many patients are likely to live
      out normal life spans if tumor control is achieved. Therefore, it is not
      sufficient simply to consider local tumor control rates and short-term toxicity
      risks when choosing between surgery, stereotactic radiosurgery, and fractionated
      radiotherapy. Patients need to be apprised of all therapeutic options and to make
      their decisions with all information required to evaluate the risks and benefits.
      For benign brain tumors, these decisions may have consequences that last for
      decades.

PMID- 16793508
TI  - Radiotoxicity after conformal radiation therapy for benign intracranial tumors.
AB  - Acoustic schwannomas, skull base meningiomas, and pituitary adenomas are benign
      intracranial tumors frequently managed with radiotherapy. Control rates after
      treatment for each of these tumors are generally high, and toxicity from
      treatment is relatively low. Side effect profiles depend on the tumor location,
      the volume treated, the dose delivered, and the presence of nearby critical
      structures. In addition, patient-specific factors, such as hypertension and
      diabetes, may increase a patient's risk for complications. This article reviews
      radiotoxicity after conformal radiation therapy for acoustic schwannomas, skull
      base meningiomas, and pituitary adenomas.

PMID- 16793509
TI  - Late neoplastic complications after radiation treatments for benign intracranial
      tumors.
AB  - There is increasing interest in the use of radiation treatment as an adjunct or
      an alternative to microsurgery in the management of a range of intracranial
      tumors. Most of these treatments are performed with linear accelerator or Gamma
      Knife systems. Precise targeting with stereotactic localization minimizes the
      volume of tissue being irradiated for single and multiple fraction irradiation.
      The incidence of secondary neoplasms after radiosurgery may be significantly less
      than that reported after whole-brain or two- or three-field radiotherapy.

PMID- 16793510
TI  - Channeling ions and hope: Cystic fibrosis foundation follows phlegmatic strategy.

PMID- 16793511
TI  - Styryl molecules light-up RNAs.
AB  - A combinatorial library of 1336 fluorescent styryl molecules was synthesized
      aiming to select dyes that are photostable, non-toxic, and specific for RNA
      molecules in living cells . These dyes are potentially important to the study of
      gene expression in live cells.

PMID- 16793512
TI  - Myxing it up to study chondramides.
AB  - Considerable progress has been achieved in elucidating the biosynthesis of
      natural products with interesting cellular targets. In this issue of Chemistry &
      Biology, Rachid et al. provide a new example, taming genetic manipulation of the
      producer of chondramide, an actin-interfering compound.

PMID- 16793513
TI  - Histone H3 lysine 4 demethylation is a target of nonselective antidepressive
      medications.
AB  - Demethylation of histone H3 lysine 4 is carried out by BHC110/LSD1, an enzyme
      with close homology to monoamine oxidases (MAO). Monoamine oxidase A or B are
      frequent targets of selective and nonselective small molecular inhibitors used
      for treatment of depression. Here we show that in contrast to selective monoamine
      oxidase inhibitors such as pargyline, nonselective monoamine oxidase inhibitors
      potently inhibit nucleosomal demethylation of histone H3 lysine 4.
      Tranylcypromine (brand name Parnate) displayed the best inhibitory activity with
      an IC50 of less than 2 microM. Treatment of P19 embryonal carcinoma cells with
      tranylcypromine resulted in global increase in H3K4 methylation as well as
      transcriptional derepression of two BHC110 target genes, Egr1 and the pluripotent
      stem cell marker Oct4. These results attest to the effectiveness of
      tranylcypromine as a small molecular inhibitor of histone demethylation.

PMID- 16793515
TI  - Genetic characterization of the chlorothricin gene cluster as a model for
      spirotetronate antibiotic biosynthesis.
AB  - The biosynthetic gene cluster for chlorothricin (CHL) was localized to a 122 kb
      contiguous DNA from Streptomyces antibioticus DSM 40725, and its involvement in
      CHL biosynthesis was confirmed by gene inactivation and complementation.
      Bioinformatic analysis of the sequenced 111.989 kb DNA region revealed 42 open
      reading frames, 35 of which were defined to constitute the CHL gene cluster. An
      assembly model for CHL biosynthesis from D-olivose, 2-methoxy-5-chloro-6
      methylsalicyclic acid, and chlorothricolide building blocks was proposed. This
      work represents cloning of a gene cluster for spirotetronate antibiotic
      biosynthesis and sets the stage to investigate the unusual macrolide biosynthesis
      including tandem Diels-Alder cyclizations, Baeyer-Villiger oxidation, and
      incorporation of an enoylpyruvate unit.

PMID- 16793514
TI  - Asteropine A, a sialidase-inhibiting conotoxin-like peptide from the marine
      sponge Asteropus simplex.
AB  - Marine sponges contain structurally intriguing and biologically active peptides
      of nonribosomal peptide synthase origin, often containing amino acids with novel
      structures. Here we report the discovery of asteropine A (APA), a cystine knot to
      be isolated from marine sponges. The solution structure of APA as determined by
      NMR belongs to the four-loop class of cystine knots similar to those of some
      conotoxins and spider toxins. However, the highly negatively charged surface of
      APA is uncommon among other cystine knots. APA competitively inhibits bacterial
      sialidases, but not a viral sialidase. APA was inactive against all other enzymes
      tested and did not have any apparent antitumor activity. Our data suggest that
      APA and other knotting peptides may be important leads for antibacterial and even
      antiviral drug development.

PMID- 16793516
TI  - The malonyl transferase activity of type II polyketide synthase acyl carrier
      proteins.
AB  - Acyl carrier proteins (ACPs) play a fundamental role in directing intermediates
      among the enzyme active sites of fatty acid and polyketide synthases (PKSs). In
      this paper, we demonstrate that the Streptomyces coelicolor (S. coelicolor)
      actinorhodin (act) PKS ACP can catalyze transfer of malonate to type II S.
      coelicolor fatty acid synthase (FAS) and other PKS ACPs in vitro. The reciprocal
      transfer from S. coelicolor FAS ACP to a PKS ACP was not observed. Several
      mutations in both act ACP and S. coelicolor FAS ACP could be classified by their
      participation in either donation or acceptance of this malonyl group. These
      mutations indicated that self-malonylation and malonyl transfer could be
      completely decoupled, implying that they were separate processes and that a FAS
      ACP could be converted from a non-malonyl-transferring protein to one with
      malonyl transferase activity.

PMID- 16793517
TI  - Tandem mass spectrometry reveals the quaternary organization of macromolecular
      assemblies.
AB  - The application of mass spectrometry (MS) to the study of progressively larger
      and more complex macromolecular assemblies is proving increasingly useful for
      structural biologists. The scope of this approach has recently been widened
      through the application of a tandem MS procedure. This two-step technique
      involves the selection of specific assemblies in the gas phase and inducing their
      dissociation through collisions with argon atoms. Here, we investigate the
      mechanism of this process and show that dissociation of subunits from a
      macromolecular assembly follows a sequential pathway, with the partitioning of
      charge between the dissociation products governed primarily by their relative
      surface areas. Using this basis of understanding, we highlight differences in the
      dissociation pathways of three related macromolecular assemblies and show how
      these are a direct consequence of changes in both local and global oligomeric
      organization.

PMID- 16793518
TI  - TMC-95-based inhibitor design provides evidence for the catalytic versatility of
      the proteasome.
AB  - TMC-95's natural cyclic tripeptide metabolites represent potent competitive
      proteasome inhibitors. The constrained conformation of TMC-95 proteasomal
      inhibitors provides the driving force for entropically high-affinity binding.
      Based on the crystal structure of the proteasome:TMC-95A complex, the
      synthetically challenging TMC-95 core structure was used for the design and
      synthesis of less demanding biphenyl-ether macrocycles, in which the biphenyl
      ether moiety functions as an endocyclic clamp restricting its tripeptide
      backbone. These simplified analogs allowed us to identify high plasticity of the
      proteasomal tryptic-like specificity pocket. Biphenyl-ether compounds extended
      with an amide group were hydrolyzed by the proteasome, although the crystal
      structure of such proteasome:biphenyl-ether complexes revealed quenching of
      proteolysis at the acyl-enzyme intermediate. Our data reveal that biphenyl-ether
      derivatives bind noncovalently to the proteasomal tryptic-like active site in a
      reversible substrate-like manner without allosteric changes of active site
      residues.

PMID- 16793519
TI  - RNA-selective, live cell imaging probes for studying nuclear structure and
      function.
AB  - The higher-order structural organization of the cell nucleus reflects the
      underlying genome-wide transcriptional activity and macromolecular transport
      processes. To study the microscopic organization of RNA distribution within the
      nucleus, a combinatorial library of fluorescent styryl molecules was synthesized
      and screened for an in vitro RNA response and live cell nuclear imaging. Four
      different cell lines (HeLa, A549, 3T3, and 3T3-L1) were analyzed in terms of
      higher-order nuclear organization. We identified RNA-selective dyes with better
      imaging properties relative to commercially available SYTORNASelect dye; the
      selected dyes were also cell permeant, photostable, and well tolerated by the
      cells. Our dyes also had very good counterstain compatibility with Hoechst and
      DAPI, which could help to image the DNA distribution in relation to RNA
      distribution in live cells and therefore reveal different patterns of RNA-DNA
      colocalization.

PMID- 16793520
TI  - Evidence for a protein-protein interaction motif on an acyl carrier protein
      domain from a modular polyketide synthase.
AB  - During biosynthesis on modular polyketide synthases (PKSs), chain extension
      intermediates are tethered to acyl carrier protein (ACP) domains through
      phosphopantetheinyl prosthetic groups. Each ACP must therefore interact with
      every other domain within the module, and also with a downstream acceptor domain.
      The nature of these interactions is key to our understanding of the topology and
      operation of these multienzymes. Sequence analysis and homology modeling
      implicates a potential helical region (helix II) on the ACPs as a protein-protein
      interaction motif. Using site-directed mutagenesis, we show that residues along
      this putative helix lie at the interface between the ACP and the
      phosphopantetheinyl transferase that catalyzes its activation. Our results accord
      with previous studies of discrete ACP proteins from fatty acid and aromatic
      polyketide biosynthesis, suggesting that helix II may also serve as a universal
      interaction motif in modular PKSs.

PMID- 16793521
TI  - Heterologous expression, purification, refolding, and structural-functional
      characterization of EP-B2, a self-activating barley cysteine endoprotease.
AB  - We describe the heterologous expression in Escherichia coli of the proenzyme
      precursor to EP-B2, a cysteine endoprotease from germinating barley seeds. High
      yields (50 mg/l) of recombinant proEP-B2 were obtained from E. coli inclusion
      bodies in shake flask cultures following purification and refolding. The zymogen
      was rapidly autoactivated to its mature form under acidic conditions at a rate
      independent of proEP-B2 concentration, suggesting a cis mechanism of
      autoactivation. Mature EP-B2 was stable and active over a wide pH range and
      efficiently hydrolyzed a recombinant wheat gluten protein, alpha2-gliadin, at
      sequences with known immunotoxicity in celiac sprue patients. The X-ray crystal
      structure of mature EP-B2 bound to leupeptin was solved to 2.2 A resolution and
      provided atomic insights into the observed subsite specificity of the
      endoprotease. Our findings suggest that orally administered proEP-B2 may be
      especially well suited for treatment of celiac sprue.

PMID- 16793522
TI  - Rational design of combination enzyme therapy for celiac sprue.
AB  - Celiac sprue (also known as celiac disease) is an inheritable, gluten-induced
      enteropathy of the upper small intestine with an estimated prevalence of 0.5%-1%
      in most parts of the world. The ubiquitous nature of food gluten, coupled with
      inadequate labeling regulations in most countries, constantly poses a threat of
      disease exacerbation and relapse for patients. Here, we demonstrate that a two
      enzyme cocktail comprised of a glutamine-specific cysteine protease (EP-B2) that
      functions under gastric conditions and a PEP, which acts in concert with
      pancreatic proteases under duodenal conditions, is a particularly potent
      candidate for celiac sprue therapy. At a gluten:EP-B2:PEP weight ratio of 75:3:1,
      grocery store gluten is fully detoxified within 10 min of simulated duodenal
      conditions, as judged by chromatographic analysis, biopsy-derived T cell
      proliferation assays, and a commercial antigluten antibody test.

PMID- 16793523
TI  - Cell-permeant small-molecule modulators of NAADP-mediated Ca2+ release.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP, 1) is the most potent
      intracellular Ca2+ mobilizing agent in important mammalian cells and tissues, yet
      the identity of the NAADP receptor is elusive. Significantly, the coenzyme NADP
      is completely inactive in this respect. Current studies are restricted by the
      paucity of any chemical probes beyond NAADP itself, and importantly, none is cell
      permeant. We report simple nicotinic acid-derived pyridinium analogs as low
      molecular weight compounds that (1) inhibit Ca2+ release via the NAADP receptor
      (IC50 approximately 15 microM - 1 mM), (2) compete with NAADP binding, (3) cross
      the cell membrane of sea urchin eggs to inhibit NAADP-evoked Ca2+ release, and
      (4) selectively ablate NAADP-dependent Ca2+ oscillations induced by the external
      gastric peptide hormone agonist cholecystokinin (CCK) in murine pancreatic acinar
      cells.

PMID- 16793524
TI  - Molecular and biochemical studies of chondramide formation-highly cytotoxic
      natural products from Chondromyces crocatus Cm c5.
AB  - The jaspamide/chondramide family of depsipeptides are mixed PKS/NRPS natural
      products isolated from marine sponges and a terrestrial myxobacterium that
      potently affect the function of the actin cytoskeleton. As a first step to
      improve production in heterologous host cells and permit genetic approaches to
      novel analogs, we have cloned and characterized the chondramide biosynthetic
      genes from the myxobacterium Chondromyces crocatus Cm c5. In addition to the
      expected PKS and NRPS genes, the cluster encodes a rare tyrosine aminomutase for
      beta-tyrosine formation and a previously unknown tryptophan-2-halogenase.
      Conditions for gene transfer into C. crocatus Cm c5 were developed, and
      inactivation of several genes corroborated their proposed function and served to
      define the boundaries of the cluster. Biochemical characterization of the final
      NRPS adenylation domain confirmed the direct activation of beta-tyrosine, and
      fluorinated chondramides were produced through precursor-directed biosynthesis.

PMID- 16793525
TI  - A critical review of the Royal Society's report on personalized medicine.

PMID- 16793526
TI  - Virtual ligand screening: strategies, perspectives and limitations.
AB  - In contrast to high-throughput screening, in virtual ligand screening (VS),
      compounds are selected using computer programs to predict their binding to a
      target receptor. A key prerequisite is knowledge about the spatial and energetic
      criteria responsible for protein-ligand binding. The concepts and prerequisites
      to perform VS are summarized here, and explanations are sought for the enduring
      limitations of the technology. Target selection, analysis and preparation are
      discussed, as well as considerations about the compilation of candidate ligand
      libraries. The tools and strategies of a VS campaign, and the accuracy of scoring
      and ranking of the results, are also considered.

PMID- 16793527
TI  - Software for computational peptide identification from MS-MS data.
AB  - Protein identification in biological samples is an important task in drug
      discovery research. Protein identification is nowadays regularly performed by
      tandem mass spectrometry (MS-MS). Because of the difficulty of measuring intact
      proteins using MS-MS, typically a protein is enzymically digested into peptides
      and the MS-MS spectrum of each peptide is measured. Computational methods are
      then invoked to identify the peptides, which are later combined together to
      identify the protein. The most recognized peptide identification software
      packages can be classified into four categories: database searching, de novo
      sequencing, sequence tagging and consensus of multiple engines.

PMID- 16793528
TI  - Designing better drugs: predicting cytochrome P450 metabolism.
AB  - Many 3D ligand-based and structure-based computational approaches have been used
      to predict, and thus help explain, the metabolism catalyzed by the enzymes of the
      cytochrome P450 superfamily (P450s). P450s are responsible for >90% of the
      metabolism of all drugs, so the computational prediction of metabolism can help
      to design out drug-drug interactions in the early phases of the drug discovery
      process. Computational methodologies have focused on a few P450s that are
      directly involved in drug metabolism. The recently derived crystal structures for
      human P450s enable better 3D modelling of these important metabolizing enzymes.
      Models derived for P450s have evolved from simple comparisons of known substrates
      to more-elaborate experiments that require considerable computer power involving
      3D overlaps and docking experiments. These models help to explain and, more
      importantly, predict the involvement of P450s in the metabolism of specific
      compounds and guide the drug-design process.

PMID- 16793529
TI  - Screening in a spirit haunted world.
AB  - High-throughput screening (HTS) campaigns can be dominated by hits that
      ultimately turn out to be non-drug-like. These "nuisance" compounds often behave
      strangely, with steep dose-response curves, absence of clear structure-activity
      relationships, and high sensitivity to assay conditions. Several mechanisms
      contribute to these artifacts, including chemically reactive molecules, those
      that absorb light in assays and those that affect redox conditions. One of the
      most common mechanisms behind artifactual inhibition is discussed in this review:
      at micromolar concentrations organic molecules can aggregate to form particles in
      aqueous buffers, and these aggregates can sequester and thereby inhibit protein
      targets. Aggregation-based inhibition is baffling from a chemical perspective,
      but viewed biophysically such behavior is expected. The range of molecules that
      behave this way, their rapid detection in a screening environment and their
      possible biological implications will be considered here.

PMID- 16793530
TI  - Cell microarrays in drug discovery.
AB  - There is an increasing need for systematic cell-based assays in a high-throughput
      screening (HTS) format to analyze the phenotypic consequences of perturbing
      mammalian cells with drugs, genes, interfering RNA. Taking advantage of the
      recent progress in microtechnology, new cell microarrays are being developed and
      applied to a large range of issues in metazoan cells. This article compares
      different approaches and evaluates their potential use in the drug discovery
      process. Although still an emerging technology, cell microarrays hold great
      promise to optimize the efficiency:cost ratio in cell-based HTS.

PMID- 16793532
TI  - Screening for positive allosteric modulators of biological targets.
AB  - The benefit of using positive allosteric modulators of protein function in the
      therapy of human diseases is becoming more apparent. The advantage of positive
      allosteric modulators is that they can possess specificity and selectivity
      profiles as well as concentration-independent limits on activity that can
      significantly reduce off-target effects in vivo. However, many current screening
      paradigms are not designed to discover positive allosteric modulators, and
      modulators that are discovered serendipitously can be overlooked during the hit
      picking process. The conditions needed to discover positive allosteric modulators
      in a HTS are reasonable and simple to implement, generally requiring
      consideration of the ligand concentration in a screen. Other considerations in
      the screening for positive allosteric modulators can be derived from the analysis
      of simple kinetic schemes that describe the interactions of ligands and
      modulators with different protein targets.

PMID- 16793531
TI  - Creating more effective antidepressants: clues from the clinic.
AB  - Antidepressant medications have eased the suffering of millions of people. In
      addition to treating depression, antidepressant drugs also treat several anxiety
      disorders. Unfortunately, there are problematic limitations with antidepressant
      agents, including a delayed therapeutic response and insufficient efficacy.
      Emerging evidence shows that atypical antipsychotic agents can be used as
      augmentation therapy in patients with poor responses to antidepressants. Future
      drugs combining key features of antidepressant and atypical antipsychotic agents
      could offer new promise for patients suffering from obsessive-compulsive
      disorder, post-traumatic stress disorder, panic disorder, generalized anxiety
      disorder and depression.

PMID- 16793533
TI  - Downscaling functional bioassays by single-molecule techniques.
AB  - In this short review we examine the potential of single-molecule assays in drug
      development and in basic research to provide new types of information at the
      smallest assay scales. A key advantage of many single-molecule assays is the
      requirement for conservative amounts of precious sample compared to conventional
      assays. In addition, they measure processes that are not observed directly in
      molecular ensembles. These advantages are balanced currently by difficulties in
      assay setup, preparation and equipment expense. However, future developments will
      ameliorate these drawbacks with the production of simpler, less expensive
      experimental systems for single-molecule assays.

PMID- 16793534
TI  - Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple
      diseases.
AB  - The Maillard reaction is a complex series of reactions that involve reducing
      sugars and proteins, giving a multitude of end-products that are known as
      advanced glycation end-products (AGEs). AGEs can contribute to the pathogenesis
      of diabetes and neurological diseases such as Alzheimer's disease. AGEs also play
      a major role in vascular stiffening, atherosclerosis, osteoarthritis,
      inflammatory arthritis and cataracts. Thus, AGE inhibitors and AGE breakers offer
      a potential strategy as therapeutics for diverse diseases. Various AGE inhibitors
      have been developed in recent years, and their underlying mechanism is based on
      the attenuation of glycoxidation and/or oxidative stress by the sequestration of
      metal ions, reactive 1,2-dicarbonyl compounds, and reactive oxygen and reactive
      nitrogen species.

PMID- 16793535
TI  - Recombinant polyclonal antibodies: the next generation of antibody therapeutics?
AB  - Antibodies have been used as therapeutics in various forms for over a century.
      Traditional immunoglobulin therapy has the advantage of reflecting the diversity
      of the natural immune response but has very limited clinical applications.
      However, over the past ten years more than 30 monoclonal antibodies have been
      successfully introduced on to the drug market. The monoclonal approach provides
      the advantage of specificity, but lacks efficacy in the treatment of diseases
      caused by complex antigens. Recombinant polyclonal antibodies, the third
      generation of antibody therapeutics, have the ability to tackle complex and
      highly mutagenic targets, and will undoubtedly offer a promising commercial
      future.

PMID- 16793536
TI  - Chemical microarray: a new tool for drug screening and discovery.
AB  - HTS with microtiter plates has been the major tool used in the pharmaceutical
      industry to explore chemical diversity space and to identify active compounds and
      pharmacophores for specific biological targets. However, HTS faces a daunting
      challenge regarding the fast-growing numbers of drug targets arising from genomic
      and proteomic research, and large chemical libraries generated from high
      throughput synthesis. There is an urgent need to find new ways to profile the
      activity of large numbers of chemicals against hundreds of biological targets in
      a fast, low-cost fashion. Chemical microarray can rise to this challenge because
      it has the capability of identifying and evaluating small molecules as potential
      therapeutic reagents. During the past few years, chemical microarray technology,
      with different surface chemistries and activation strategies, has generated many
      successes in the evaluation of chemical-protein interactions, enzyme activity
      inhibition, target identification, signal pathway elucidation and cell-based
      functional analysis. The success of chemical microarray technology will provide
      unprecedented possibilities and capabilities for parallel functional analysis of
      tremendous amounts of chemical compounds.

PMID- 16793539
TI  - Destabilizing heterochromatin: Does Swi6/HP1 make the choice?
AB  - HP1 is well known as a key silencing protein. However, in the June 9 issue of
      Molecular Cell, report that Swi6/HP1 recruits an antisilencing protein, Epe1, to
      facilitate transcription, leading to a model in which Swi6/HP1 is used as a
      platform to recruit both silencing and antisilencing activities.

PMID- 16793540
TI  - How Rho exerts its muscle on RNA.
AB  - Rho factor in bacteria terminates transcription by using energy from ATP
      hydrolysis to forcefully dissociate the transcripts from RNA polymerase. used
      data from presteady-state ATPase kinetics to support a rational mechanistic model
      for Rho's action on RNA.

PMID- 16793541
TI  - p97: The cell's molecular purgatory?
AB  - The multifunctional AAA-ATPase p97/VCP is one of the most extensively studied
      members of this protein family, yet it presents the field with many perplexing
      questions surrounding its mechanism of substrate engagement and processing.
      Recent discoveries have unmasked a new purgatorial identity for this molecule in
      the ubiquitin-proteasome pathway, specifically its role in linking ubiquitylated
      substrates with competing ubiquitin conjugation and deconjugation machineries.
      Furthermore, biochemical studies surprisingly identify the C-terminal D2 ring as
      essential for substrate interaction, thus bringing p97 one step closer to its
      prokaryotic AAA protease relatives.

PMID- 16793542
TI  - Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2.
AB  - BRCA2 mutations predispose carriers to breast and ovarian cancer and can also
      cause other cancers and Fanconi anemia. BRCA2 acts as a "caretaker" of genome
      integrity by enabling homologous recombination (HR)-based, error-free DNA double
      strand break repair (DSBR) and intra-S phase DNA damage checkpoint control.
      Described here is the identification of PALB2, a BRCA2 binding protein. PALB2
      colocalizes with BRCA2 in nuclear foci, promotes its localization and stability
      in key nuclear structures (e.g., chromatin and nuclear matrix), and enables its
      recombinational repair and checkpoint functions. In addition, multiple, germline
      BRCA2 missense mutations identified in breast cancer patients but of heretofore
      unknown biological/clinical consequence appear to disrupt PALB2 binding and
      disable BRCA2 HR/DSBR function. Thus, PALB2 licenses key cellular biochemical
      properties of BRCA2 and ensures its tumor suppression function.

PMID- 16793543
TI  - Structure of the Tfb1/p53 complex: Insights into the interaction between the
      p62/Tfb1 subunit of TFIIH and the activation domain of p53.
AB  - The interaction between the amino-terminal transactivation domain (TAD) of p53
      and TFIIH is directly correlated with the ability of p53 to activate both
      transcription initiation and elongation. We have identified a region within the
      p53 TAD that specifically interacts with the pleckstrin homology (PH) domain of
      the p62 and Tfb1 subunits of human and yeast TFIIH. We have solved the 3D
      structure of a complex between the p53 TAD and the PH domain of Tfb1 by NMR
      spectroscopy. Our structure reveals that p53 forms a nine residue amphipathic
      alpha helix (residues 47-55) upon binding to Tfb1. In addition, we demonstrate
      that diphosphorylation of p53 at Ser46 and Thr55 leads to a significant
      enhancement in p53 binding to p62 and Tfb1. These results indicate that a
      phosphorylation cascade involving Ser46 and Thr55 of p53 could play an important
      role in the regulation of select p53 target genes.

PMID- 16793544
TI  - Structural basis of DNA recognition by p53 tetramers.
AB  - The tumor-suppressor protein p53 is among the most effective of the cell's
      natural defenses against cancer. In response to cellular stress, p53 binds as a
      tetramer to diverse DNA targets containing two decameric half-sites, thereby
      activating the expression of genes involved in cell-cycle arrest or apoptosis.
      Here we present high-resolution crystal structures of sequence-specific complexes
      between the core domain of human p53 and different DNA half-sites. In all
      structures, four p53 molecules self-assemble on two DNA half-sites to form a
      tetramer that is a dimer of dimers, stabilized by protein-protein and base
      stacking interactions. The protein-DNA interface varies as a function of the
      specific base sequence in correlation with the measured binding affinities of the
      complexes. The new data establish a structural framework for understanding the
      mechanisms of specificity, affinity, and cooperativity of DNA binding by p53 and
      suggest a model for its regulation by regions outside the sequence-specific DNA
      binding domain.

PMID- 16793545
TI  - Chromosomal association of the Smc5/6 complex reveals that it functions in
      differently regulated pathways.
AB  - The SMC protein complexes safeguard genomic integrity through their functions in
      chromosome segregation and repair. The chromosomal localization of the budding
      yeast Smc5/6 complex determined here reveals that the complex works specifically
      on the duplicated genome in differently regulated pathways. The first controls
      the association to centromeres and chromosome arms in unchallenged cells, the
      second regulates the association to DNA breaks, and the third directs the complex
      to the chromosome arm that harbors the ribosomal DNA arrays. The chromosomal
      interaction pattern predicts a function that becomes more important with
      increasing chromosome length and that the complex's role in unchallenged cells is
      independent of DNA damage. Additionally, localization of Smc6 to collapsed
      replication forks indicates an involvement in their rescue. Altogether this shows
      that the complex maintains genomic integrity in multiple ways, and evidence is
      presented that the Smc5/6 complex is needed during replication to prevent the
      accumulation of branched chromosome structures.

PMID- 16793546
TI  - Comparative analysis identifies exonic splicing regulatory sequences--The complex
      definition of enhancers and silencers.
AB  - Exonic splicing regulatory sequences (ESRs) are cis-acting factor binding sites
      that regulate constitutive and alternative splicing. A computational method based
      on the conservation level of wobble positions and the overabundance of sequence
      motifs between 46,103 human and mouse orthologous exons was developed,
      identifying 285 putative ESRs. Alternatively spliced exons that are either short
      in length or contain weak splice sites show the highest conservation level of
      those ESRs, especially toward the edges of exons. ESRs that are abundant in those
      subgroups show a different distribution between constitutively and alternatively
      spliced exons. Representatives of these ESRs and two SR protein binding sites
      were shown, experimentally, to display variable regulatory effects on alternative
      splicing, depending on their relative locations in the exon. This finding
      signifies the delicate positional effect of ESRs on alternative splicing
      regulation.

PMID- 16793547
TI  - The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis.
AB  - Cellular senescence and apoptosis have evolved to restrain unwarranted
      proliferation of potentially tumorigenic cells. Here we show that overexpression
      of the E3 SUMO ligase PIASy in normal human fibroblasts recruits the p53 and Rb
      tumor suppressor pathways to provoke a senescence arrest. By contrast, in Rb
      deficient fibroblasts, expression of PIASy leads to p53-dependent apoptosis.
      Induction of senescence requires PIASy E3 activity and is specific for this
      member of the PIAS ligase family. PIASy stimulates sumoylation and
      transcriptional activity of p53 and increases Rb-dependent corepression through
      recruitment to E2F-responsive promoters. Viral oncoprotein E6 suppresses both
      PIASy-induced senescence and sumoylation of PIASy substrates. Finally, we show
      that fibroblasts lacking PIASy exhibit a highly reduced propensity to undergo
      senescence in response to a prosenescence stimulus. Altogether, these data
      provide the first evidence for a direct role of an E3 SUMO ligase, and by
      implication of the SUMO pathway, in cellular senescence and apoptosis.

PMID- 16793548
TI  - IRBIT suppresses IP3 receptor activity by competing with IP3 for the common
      binding site on the IP3 receptor.
AB  - The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-gated
      intracellular Ca2+ channels. We previously identified an IP3R binding protein,
      IRBIT, which binds to the IP3 binding domain of IP3R and is dissociated from IP3R
      in the presence of IP3. In the present study, we showed that IRBIT suppresses the
      activation of IP3R by competing with IP3 by [3H]IP3 binding assays, in vitro Ca2+
      release assays, and Ca2+ imaging of intact cells. Multiserine phosphorylation of
      IRBIT was essential for the binding, and 10 of the 12 key amino acids in IP3R for
      IP3 recognition participated in binding to IRBIT. We propose a unique mode of
      IP3R regulation in which IP3 sensitivity is regulated by IRBIT acting as an
      endogenous "pseudoligand" whose inhibitory activity can be modulated by its
      phosphorylation status.

PMID- 16793549
TI  - Is dimerization required for the catalytic activity of bacterial biotin
      carboxylase?
AB  - Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid
      metabolism. The biotin carboxylase (BC) subunit of Escherichia coli ACC is
      believed to be active only as a dimer, although the crystal structure shows that
      the active site of each monomer is 25 A from the dimer interface. We report here
      biochemical, biophysical, and structural characterizations of BC carrying single
      site mutations in the dimer interface. Our studies demonstrate that two of the
      mutants, R19E and E23R, are monomeric in solution but have only a 3-fold loss in
      catalytic activity. The crystal structures of the E23R and F363A mutants show
      that they can still form the correct dimer at high concentrations. Our data
      suggest that dimerization is not an absolute requirement for the catalytic
      activity of the E. coli BC subunit, and we propose a new model for the molecular
      mechanism of action for BC in multisubunit and multidomain ACCs.

PMID- 16793550
TI  - The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the
      yeast RasGAP neurofibromin homologs Ira1 and Ira2.
AB  - The G protein-coupled receptor Gpr1 and associated Galpha subunit Gpa2 govern
      dimorphic transitions in response to extracellular nutrients by signaling
      coordinately with Ras to activate adenylyl cyclase in the yeast Saccharomyces
      cerevisiae. Gpa2 forms a protein complex with the kelch Gbeta mimic subunits
      Gpb1/2, and previous studies demonstrate that Gpb1/2 negatively control cAMP-PKA
      signaling via Gpa2 and an unknown second target. Here, we define these targets of
      Gpb1/2 as the yeast neurofibromin homologs Ira1 and Ira2, which function as
      GTPase activating proteins of Ras. Gpb1/2 bind to a conserved C-terminal domain
      of Ira1/2, and loss of Gpb1/2 results in a destabilization of Ira1 and Ira2,
      leading to elevated levels of Ras2-GTP and unbridled cAMP-PKA signaling. Because
      the Gpb1/2 binding domain on Ira1/2 is conserved in the human neurofibromin
      protein, an analogous signaling network may contribute to the neoplastic
      development of neurofibromatosis type 1.

PMID- 16793551
TI  - Donor-strand exchange in chaperone-assisted pilus assembly proceeds through a
      concerted beta strand displacement mechanism.
AB  - Gram-negative pathogens commonly use the chaperone-usher pathway to assemble
      adhesive multisubunit fibers on their surface. In the periplasm, subunits are
      stabilized by a chaperone that donates a beta strand to complement the subunits'
      truncated immunoglobulin-like fold. Pilus assembly proceeds through a "donor
      strand exchange" (DSE) mechanism whereby this complementary beta strand is
      replaced by the N-terminal extension (Nte) of an incoming pilus subunit. Using X
      ray crystallography and real-time electrospray ionization mass spectrometry (ESI
      MS), we demonstrate that DSE requires the formation of a transient ternary
      complex between the chaperone-subunit complex and the Nte of the next subunit to
      be assembled. The process is crucially dependent on an initiation site (the P5
      pocket) needed to recruit the incoming Nte. The data also suggest a capping
      reaction displacing DSE toward product formation. These results support a zip-in
      zip-out mechanism for DSE and a catalytic role for the usher, the molecular
      platform at which pili are assembled.

PMID- 16793552
TI  - Native hepatitis B virions and capsids visualized by electron cryomicroscopy.
AB  - Hepatitis B virus (HBV) infects more than 350 million people, of which one
      million will die every year. The infectious virion is an enveloped capsid
      containing the viral polymerase and double-stranded DNA genome. The structure of
      the capsid assembled in vitro from expressed core protein has been studied
      intensively. However, little is known about the structure and assembly of native
      capsids present in infected cells, and even less is known about the structure of
      mature virions. We used electron cryomicroscopy (cryo-EM) and image analysis to
      examine HBV virions (Dane particles) isolated from patient serum and capsids
      positive and negative for HBV DNA isolated from the livers of transgenic mice.
      Both types of capsids assembled as icosahedral particles indistinguishable from
      previous image reconstructions of capsids. Likewise, the virions contained
      capsids with either T = 3 or T = 4 icosahedral symmetry. Projections extending
      from the lipid envelope were attributed to surface glycoproteins. Their packing
      was unexpectedly nonicosahedral but conformed to an ordered lattice. These
      structural features distinguish HBV from other enveloped viruses.

PMID- 16793553
TI  - The human and mouse complement of SH2 domain proteins-establishing the boundaries
      of phosphotyrosine signaling.
AB  - SH2 domains are interaction modules uniquely dedicated to the recognition of
      phosphotyrosine sites and are embedded in proteins that couple protein-tyrosine
      kinases to intracellular signaling pathways. Here, we report a comprehensive
      bioinformatics, structural, and functional view of the human and mouse complement
      of SH2 domain proteins. This information delimits the set of SH2-containing
      effectors available for PTK signaling and will facilitate the systems-level
      analysis of pTyr-dependent protein-protein interactions and PTK-mediated signal
      transduction. The domain-based architecture of SH2-containing proteins is of more
      general relevance for understanding the large family of protein interaction
      domains and the modular organization of the majority of human proteins.

PMID- 16793554
TI  - Usefulness of a body composition analyzer, InBody 2.0, in chronic hemodialysis
      patients.
AB  - The objective of the present study was to investigate whether InBody 2.0 might be
      useful in measuring the dry weight of chronic hemodialysis (HD) patients. Thirty
      five HD patients (22 males and 13 females; mean age 62.6 +/- 14.0 years; mean HD
      duration 101.0 +/- 118.06 months) were examined. Multifrequency bioelectric
      impedance analysis was used to estimate the ratio of extracellular water (ECW) to
      total body water (TBW). The body resistance was measured at frequencies ranging
      from 1 kHz to 1 MHz. The impedance index was determined at a low frequency (5
      kHz) and correlated closely with ECW, using sodium bromide dilution as standard
      comparison. The levels of serum albumin, prealbumin, total cholesterol (TC),
      triglycerides (TG), transferrin, and human atrial natriuretic peptide (hANP) were
      measured by routine methods in our hospital. The ECW/TBW ratio was significantly
      associated with the levels of hANP (p < 0.05). However, no associations between
      the levels of serum albumin, TC, TG, or transferrin and the ECW/TBW were
      observed. It appears that the body composition analyzer, InBody 2.0, may be
      useful for estimating the dry weight in chronic HD patients.

PMID- 16793555
TI  - Clinical features of fatal asthma.
AB  - To characterize the clinical features of fatal asthma, we retrospectively
      analyzed the clinical characteristics of patients who died of an acute asthma
      attack in our hospital during a 15-year period from 1989 to 2003. Twelve patients
      had fatal asthma during this period, including eight who were dead on arrival in
      the emergency room (ER) and three who died within 1 hour of admission to the ER.
      Patients were categorized into three groups according to the clinical
      presentations during the fatal attack: (1) rapid (< 3 hours) decompensation in
      four patients; (2) gradual development of respiratory failure over several days
      in two patients; and (3) acute deterioration after unstable asthma lasting
      several days in six patients. All patients in groups 1 and 2 had reported
      previous near-fatal attacks. The proportion of young patients was highest in
      group 3, with half of them (3/6) younger than 35 years of age. Only one patient
      in group 3 had had a previous near-fatal attack. Five of the seven patients, with
      previous near-fatal attacks, had a pattern of decompensation during their fatal
      attack that was similar to their previous attacks. In conclusion, nearly all
      patients with fatal asthma in this study died outside of the hospital or within 1
      hour after admission to the ER. Patients had patterns of decompensation during
      the fatal attack that were similar to those of their previous attacks. Early
      detection of warning signs, early admission to the ER, adequate treatment, and
      extremely close observation of patients, especially within 1 hour after ER
      arrival, may prevent or decrease the incidence of fatal asthmatic attack.

PMID- 16793556
TI  - Invasive fungal infections in patients with acute leukemia.
AB  - Invasive fungal infections, a serious problem among cancer patients, are
      increasing in incidence, and can cause morbidity and mortality. Such infections
      may hinder additional treatment, especially for patients with leukemia. We report
      here our experiences in the management of invasive fungal infection in patients
      with acute leukemia. A total of 18 patients were enrolled in the study: 12 had
      microabscesses of the liver and/or spleen and/or kidneys; four had sinonasal
      infections; and two had pulmonary infections. Most of the patients (88.9%)
      received amphotericin B during treatment for fungal infection. Thirteen patients
      achieved complete response without evidence of fungal infection in follow-up. In
      the study, there were 11 mortalities, including five patients who died during
      therapy and six who later died as a result of relapse or refractoriness of the
      leukemia. We suggest that many patients may have a good response to antifungal
      therapy, and that fungal infection does not have to preclude additional
      chemotherapy after proper management. The state of the underlying disease has a
      strong impact on outcome.

PMID- 16793557
TI  - A comparative study of three fecal occult blood tests in upper gastrointestinal
      bleeding.
AB  - The purpose of this study was to evaluate the performance characteristics of
      three fecal occult blood tests (FOBTs): the chemical o-toluidine test, the
      immunochemical OC-Hemodia test, and the immunochromatographic Quick Chaser Occult
      Blood (QCOB) test, which detect human hemoglobin and transferrin simultaneously
      in cases of upper gastrointestinal (GI) bleeding. Included were 48 FOBT specimens
      in 48 consecutive admission cases of upper GI bleeding (endoscopy confirmed). We
      excluded those fecal specimens with an obvious tarry and bloody appearance. The
      QCOB test revealed the highest positive rates of 33/48 (68.8%), and significantly
      higher positive rates than that of the OC-Hemodia test and o-toluidine test (p <
      0.025 and < 0.01, respectively). In the patient group with upper GI bleeding due
      to gastric and duodenal ulcers, the QCOB test had higher positive rates (68.6%)
      than did the o-toluidine test (34.3%) (p < 0.01). There was no fecal specimen
      that was positive for the o-toluidine test or OC-Hemodia test and was negative
      for the QCOB test. Our results reveal that the QCOB test has significantly higher
      positive rates of fecal occult blood than either the OC-Hemodia test or o
      toluidine test. The QCOB test is better than the other two tests for detecting
      occult blood in patients with upper GI bleeding.

PMID- 16793558
TI  - Stratus optical coherence tomography for evaluating optic disc pits associated
      with maculopathy before and after vitrectomy: two case reports.
AB  - Optic disc pit (ODP) can be either congenital or acquired. Congenital ODP is
      typically unilateral, and the visual acuity and visual field are normal unless
      associated with macular serous detachment, which occurs in about 25-75% of cases.
      Acquired ODP is known as an important risk factor for progressive visual field
      loss in glaucoma. The fundus finding of congenital ODP includes oval depression
      involving the optic disc, with or without macular serous detachment. We used
      third-generation Stratus optical coherence tomography (Straus OCT) to investigate
      the possible pathogenesis of ODP associated with maculopathy and to monitor the
      anatomic changes before and after treatment.

PMID- 16793559
TI  - Immunohistochemical expression in male breast cancer: two case reports.
AB  - Male breast cancer is rare, and the incidence is less than 1% of all breast
      malignancies in both men and women. It is possible that, because male patients
      are unaware of male breast cancer, there is a delay of diagnosis and,
      consequently, more advanced stages are commonly encountered in these patients.
      Some studies have engaged in molecular studies of male breast cancers because of
      the possibly different characteristics, prognosis, and treatment between male and
      female malignancies. However, a dearth of studies still exists, most likely
      because of the rarity of the disease and lack of a large patient base for study.
      Among the molecular markers of breast cancer, p53, Ki-67, HER-2/neu, and Bcl-2
      are the most frequently studied. Here we present two rare cases and a review of
      the literature concerning the relationship between immunohistochemical markers
      and their impact in order to provide surgeons with more information about the
      disease and further techniques for treatment of these patients.

PMID- 16793560
TI  - Hair as the nidus for bladder calculi formation complicating suprapubic
      cystostomy catheterization: a case report.
AB  - Neurogenic bladder is a familiar sequel to spinal cord injury, and bladder
      calculi is a common complication of neurogenic bladder. We report a case of a 25
      year-old man with spinal cord injury resulting in neurogenic bladder. Permanent
      cystostomy was performed, and, for 4 years, the patient received periodic
      replacement of a cystostomy catheter. Bladder calculi were found on follow-up
      radiography. Cystoscopic lithotripsy was done, and it was noted that a hair was
      the nidus of a calculus. The hair could have been introduced into the bladder
      accidentally during the cystostomy catheter replacement. We suggest routine pubic
      hair care, even shaving, for patients suffering from neurogenic bladder with
      cystostomy. In addition, patients and caregivers should take care not to
      introduce pubic hair into the bladder while changing cystostomy catheters.

PMID- 16793561
TI  - Modified gunderson conjunctival flap combined with an oral mucosal graft to treat
      an intractable corneal lysis after chemical burn: a case report.
AB  - Following a severe chemical injury, persistent corneal melting presents as a
      threatening condition for loss of vision or the eyeball itself. Keratoplasty
      (both lamellar and penetrating) and amniotic membrane transplantation have been
      the usual modes of therapy. However, these may not halt the persistent melting
      process. We introduce here an alternative surgical procedure to resolve corneal
      melting and preserve the globe. This case concerns the right eye of a 36-year-old
      male who had suffered from severe ocular alkali chemical burns and sustained
      intractable corneal melting, despite receiving corneal transplants three times, a
      limbal stem cell transplantation once, a scleral graft twice, and amniotic
      membrane transplantation eight times. To circumvent the impending perforation, we
      performed a modified Gunderson conjunctival flap combined with an oral mucosal
      graft. The corneal melting was halted, and the eyeball was preserved. The
      combination of an oral mucosal graft to the modified Gunderson conjunctival flap
      provided an easy alternative to resolve a case of intractable corneal melting and
      impending perforation.

PMID- 16793562
TI  - Randomized comparative study of the effects of treatment with once-daily, niacin
      extended-release/lovastatin and with simvastatin on lipid profile and
      fibrinolytic parameters in Taiwan.
AB  - Hyperlipidemia can be effectively treated either with niacin or HMG-CoA reductase
      inhibitor (statin), or a combination of both. Few reports showed the effects of
      the combination regimen with niacin and statin on hemostatic functions. We
      conducted a single-center, double-blind, double-dummy, randomized, two-arm study
      to assess the effects of the niacin extended-release/lovastatin therapy in a
      fixed-dose formulation and of simvastatin on lipid lowering and two fibrinolytic
      parameters, fibrinogen and d-dimer. All patients were enrolled according to NCEP
      ATP III guidelines and underwent a placebo run-in period of 4 weeks before being
      randomized to either niacin extended-release/lovastatin tablets (500/20 mg) once
      daily (n = 36) or simvastatin capsule (20 mg) once daily (n = 34). After 16 weeks
      of treatment, both groups of patients showed significantly reduced low-density
      lipoprotein cholesterol and total cholesterol (LDL-C, p < 0.001 and < 0.001,
      respectively, p = 0.159 between the groups; TC, p < 0.001 and < 0.001,
      respectively, p = 0.018 between the groups). Both drugs were well tolerated. Only
      in the group treated with niacin extended-release/lovastatin was fibrinogen
      concentration significantly reduced after treatment (2.48 +/- 0.65 to 1.99 +/-
      0.62 g/L, p = 0.008). No difference was found with d-dimer in either group. This
      study shows that both niacin extended-release/lovastatin and simvastatin are
      effective and well-tolerated lipid-lowering drugs in Taiwanese patients with
      dyslipidemia. A combinational treatment with niacin extended-release/lovastatin
      may provide additional benefit in fibrinolysis.

PMID- 16793563
TI  - Rescula as an alternative therapy for beta-blockers with long-term drift effect
      in glaucoma patients.
AB  - The purpose of this study was to evaluate both the intraocular pressure (IOP)
      decreasing and neuroprotective effects of Rescula (0.12% unoprostone isopropyl)
      as an alternative therapy to betablockers with a long-term drift effect in
      patients with glaucoma. Twenty-eight patients with unilateral or bilateral
      glaucoma were treated with Rescula instead of the original beta-blocker therapy.
      IOP was measured using a Goldmann applanation tonometer, and visual field defects
      were evaluated quantitatively by Humphrey automatic perimetry central 30-2
      threshold test. The mean follow-up time was at least 1 year. Rescula achieved a
      significant (p = 0.00001) and long-lasting reduction in IOP (from 20.78 +/- 2.71
      to 17.14 +/- 2.70 mmHg) in patients with open-angle glaucoma after 12 months of
      follow-up. It also demonstrated a significant (p = 0.02) IOP-reducing effect
      (from 20.67 +/- 3.60 to 16.36 +/- 3.67 mmHg) in patients with angle-closure
      glaucoma 12 months later. The mean deviation of visual field defects changed from
      -13.27 dB baseline to -10.64 dB at 12 months as evaluated by Humphrey field
      analyzer II central 30-2 threshold test after Rescula; however, there was no
      statistical difference (p = 0.098). Our results showed that Rescula has a
      significant IOP-reducing effect as an alternative therapy to beta-blockers with
      long-term drift effect in patients with open-angle and angle-closure glaucoma.
      However, a neuroprotective effect to prevent further progression of the visual
      field defect in patients with glaucoma was not demonstrated in this study.

PMID- 16793564
TI  - Self-perceived quality of life for adolescents with physical disabilities - a
      preliminary study.
AB  - The purpose of this study was to explore the effect of physical disabilities (PD)
      on the quality of life (QoL) of adolescents aged from 10 to 18 years. Sixty-three
      adolescents with PD (aged 14.9 +/- 2.4 years) from primary (5th grade or above)
      to high schools in Kaohsiung City volunteered to participate in this research;
      282 children without disability (aged 13.8 +/- 2.3 years) attending schools in
      the same geographical region were recruited as controls. The Student Version of
      the Comprehensive Quality of Life Scale was used in this study. This is a
      multidimensional self-report, global measure of subjective and objective QoL.
      Multivariate analysis of variance revealed that the two groups were significantly
      different in objective QoL (F = 11.53, p < 0.001). Material wellbeing was
      substantially lower in the PD group when compared to the control group. In
      contrast, domains such as productivity, safety, and emotion were higher in the PD
      group. Among the subjective scales, the PD group showed higher productivity and
      better emotion when compared to the control group. No significant correlation was
      observed between objective and subjective overall QoL scores (r = 0.20, p = 0.12)
      in the PD group. These findings showed that subjects with PD in regular schools
      demonstrated different patterns in objective and subjective QoL when compared to
      those without PD. Both subjective and objective domains are important when
      measuring QoL of adolescents with PD.

PMID- 16793565
TI  - Gender differences in hazard rate affecting death in the elderly population in
      Taiwan.
AB  - As the age-specific mortality of women is lower than that of men, feminization of
      later life is becoming common in all societies. Although elderly women enjoy
      lower mortality, the health status of women is not necessarily better than that
      of men. In this study, the mortality change, characteristics of the elderly
      population, and the trend of feminization in later life in Taiwan was reviewed.
      Various measures which are used to analyze the gender differences of health
      status among Taiwan's elderly, and estimation of the effects of factors
      influencing health were discussed using data from The Survey of Health and Living
      Status of the Elderly in Taiwan, published by The Department of Health in the
      Bureau of Health Promotion. The patterns of diseases, functional status, self
      rated health and causal relationships among them were also investigated. The
      hazard rate model was employed to compare the dynamics of health and the
      functional status for men and women. The probability of being institutionalized
      and/or death for women is lower than for men for all functional status. However,
      the health status of women is not significantly better than men. Elderly women
      are less affected by fatal diseases but have more benign diseases restricting
      motion and function, which unexpectedly extends the effects of being more
      cautious, and, therefore, women live longer. The influence of self-rated health
      and functional status to hazard rate of death for both genders was equivalent and
      coincides with what was previously anticipated.

PMID- 16793566
TI  - St-segment elevation acute myocardial infarction in a patient with acromegaly: a
      case report and literature review.
AB  - Acromegaly is a disorder caused by the excess production of pituitary growth
      hormone and is characterized by the enlargement of the hands, feet and head.
      Increased morbidity and mortality with acromegaly is associated with
      cardiovascular complications, hypertension, glucose intolerance, cardiomyopathy
      and coronary artery disease. We report a case of acromegaly, which presented with
      ST-segment elevation acute myocardial infarction. The patient received successful
      primary transluminal coronary angioplasty with stent implantation. Acromegaly was
      suspected from typical appearance, and confirmed with hormonal examination and
      imaging of the pituitary mass. We discuss this case in comparison with previous
      literature.

PMID- 16793567
TI  - Neurofibroma derived from the deep peroneal nerve: a case report.
AB  - Neurofibromas may arise anywhere along a nerve from the dorsal root ganglion to
      the terminal nerve branches; however, peroneal nerve involvement is not common.
      Surgical resection of neurofibroma with total preservation of nerve function had
      been thought to be difficult. Here, we report a case of an intermuscular
      intraneural neurofibroma derived from the deep peroneal nerve in a patient with
      neurofibromatosis type 1. The diagnostic criteria, characteristics of imaging
      studies, and operative approach are described. The function of the deep peroneal
      nerve was preserved, with satisfactory results.

PMID- 16793568
TI  - Subacute thyroiditis following influenza vaccine (Vaxigrip) in a young female.
AB  - Subacute thyroiditis (SAT), also called de Quervain thyroiditis or granulomatous
      thyroiditis, is a self-limiting, possibly viral, and inflammatory thyroid
      disorder that is usually associated with thyroid pain and systemic symptoms. This
      report details a case of SAT possibly associated with influenza vaccine
      (Vaxigrip) in a young female. The diagnosis, therapeutic management and outcome
      are discussed.

PMID- 16793569
TI  - Huge aggressive angiomyxoma: a case report and literature review.
AB  - Angiomyxoma occurs mostly in 30- to 40-year-old females and is described
      histologically as a mesenchymal tumor, composed of fibroblasts within a strong
      myxoid background. It occurs mainly in the female pelvis, vulva or perineum, and
      grows slowly. Treatment is surgical excision. Unfortunately, there is a
      relatively high rate of recurrence because the exact extent of the tumor is
      difficult for the surgeon to determine. We report a case of aggressive
      angiomyxoma combined with uterine myoma, and discuss the characteristics of its
      images. Surgical excision of the tumor was performed, and adjuvant treatment was
      given for local recurrence.

PMID- 16793570
TI  - Basic developmental rules and their implications for epilepsy in the immature
      brain.
AB  - The construction of the human brain with its 10(15) synapses follows a set of
      complex developmentally and environmentally regulated steps. A series of
      sequences have been described that are instrumental, in the sense that a failure
      of any one of them leads to dramatic, life-long consequences. Hence the
      importance of determining the sequential maturation of neurons, synapses and
      cortical maps. It is also important to determine how network-driven events become
      installed, as neuronal activity intervenes in all of these steps and modulates,
      for better or worse, the outcome. A fundamental consequence of these sequential
      events is that any disruption will have very different consequences depending on
      when it occurs, indeed, "when is as important as what". An obvious aspect of
      these general features is related to seizures. In fact, the developing brain has
      both a higher incidence of seizures in human and animal models, and experiences
      seizures that can produce long-lasting consequences that are also stage
      dependent. This seminar and the series of slides presented are an introduction to
      these issues, summing up several studies made notably by INMED researchers during
      the last two decades (http://www.inmednet.com). It concentrates on four basic
      developmental rules: i) the generation by very immature neurons, of very large
      currents mediated by the activation of receptors in neurons that bear no
      synapses. This is due to the release of GABA that diffuses to distal sites and
      acts as a paracrine factor; ii) the excitatory/inhibitory shift of the actions of
      GABA during development because of a progressive reduction in the intracellular
      chloride concentration; iii) the sequential formation of GABAergic synapses and
      networks before glutamatergic ones, implying that, at an early stage, all the
      excitatory drive will be GABAergic; iv) the presence, at an early stage, of a
      unique, primitive pattern in all developing structures, this pattern disappears
      when most GABAergic synapses have shifted to their adult configuration. Several
      consequences of these sequences are described including: i) a control of neuronal
      migration by GABA-acting drugs, and the possibility that migration disorders are
      also generated by environmental factors that include the effects of GABA-acting
      agents; ii) If GABA excites immature neurons and inhibits adult one, then GABA
      acting agents will also produce different effects on the mother and the embryo;
      iii) early brain oscillations are generated by the periphery and propagate
      centrally - notably to the sensory-motor cortex, suggesting that peripherally
      generated movements may provide an important signal for the formation of cortical
      maps, in keeping with the importance of embryonic movements; iv) "seizures beget
      seizures" in the developing brain. This has now been shown in a triple chamber
      with the two intact hippocampi that we developed, and with which it has been
      possible to show that only recurrent seizures that include high frequency
      oscillations can transform the naive, contralateral hippocampus to an epileptic
      one that seizes spontaneously. Most interestingly, at an early developmental
      stage, when GABA excites many neurons and the density of glutamatergic synapses
      is not sufficiently high, purely glutamatergic seizures cannot lead to long-term
      consequences, the additional excitatory drive provided by GABAergic synapses is
      needed. In other words, at that stage, blocking GABA synapses generates seizures,
      as in adults, but these do not lead to long-term consequences. The mechanisms
      that underlie these differences is due to the need for high frequency
      oscillations (> 80 Hz or so), and these can only be generated when GABA synapses
      are operative in the developing brain: GABA receptor antagonists are ictogenic,
      but not epileptogenic. To facilitate teaching purposes the paper is published
      together with supplemental data (as a PowerPoint presentation included in the
      accompanying DVD), thus allowing an overview of important developmental steps and
      their implications.

PMID- 16793571
TI  - Implacable images: why epileptiform events continue to be featured in film and
      television.
AB  - Epileptiform events have been portrayed in film since 1900 and on television
      since the 1950's. Over time, portrayals have not reflected medicine's
      understanding of epilepsy. At present, it is unlikely that individuals who do not
      have a close relationship with someone with a seizure-disorder will witness a
      seizure. Because fictive and often incorrect images appear increasingly, many
      think of them as accurate depictions. The research addresses three questions in
      relation to these images: How do directors use the images? Why do uses of
      seizures in visual media not reflect contemporary scientific knowledge? Why have
      they persisted and increased in use? Data consist of material from 192 films and
      television episodes. The general category of seizures includes seizures in
      characters said to have epilepsy or some other condition, seizures related to
      drug or alcohol use, pseudoseizures and feigned seizures, and, a category in
      which, for example, someone is described as "having a fit." The research
      demonstrates how epileptiform events drive the narrative, support the genre,
      evoke specific emotional reactions, accentuate traits of characters with
      seizures, highlight qualities of other characters through their responses to the
      seizures, act as catalysts for actions, and enhance the voyeuristic experience of
      the audience. Twenty video sequences are included in the manuscript. The authors
      conclude that the visual experience of seizures remains so enthralling that its
      use is most likely to increase particularly on television, and that as the public
      has less experience with real seizures, depictions in film will continue to be
      more concerned with what the image can do for the show and less interested in
      accurate portrayals. Ways to influence depictions are suggested.

PMID- 16793572
TI  - Lingual epilepsia partialis continua in Rasmussen's encephalitis.
AB  - We report an adult male who presented with disabling dysarthria due to epilepsia
      partialis continua (EPC) of the left half of the tongue. The clinical, brain
      magnetic resonance imaging and electroencephalographic features were consistent
      with Rasmussen's encephalitis, although, despite having had the disease for over
      15 years, he did not exhibit any hemiparesis. The accompanying video illustrates
      the lingual EPC and its total resolution following a right frontal opercular
      focal cortical resection.

PMID- 16793573
TI  - Measurement of seizure freedom in adjunctive therapy studies in refractory
      partial epilepsy: the levetiracetam experience.
AB  - PURPOSE: To assess the advantages and disadvantages of six methodologies used in
      calculating seizure freedom rates in placebo-controlled, adjunctive therapy
      trials of new antiepileptic drugs (AEDs) in partial epilepsy, and two
      methodologies for long-term follow-up studies. METHODS: Data from levetiracetam
      trials were used to illustrate the impact of different methodologies on seizure
      freedom rates. Seizure-freedom data for several new AEDs were identified from the
      published medical literature using MEDLINE and from a recent comprehensive
      textbook. RESULTS: Most randomized, placebo-controlled add-on clinical trials of
      new AEDs contain little or no information about seizure freedom. Importantly, the
      methodology used can profoundly affect results when calculating seizure-free
      rates. Seizure freedom data should be reported as well as the methodology used.
      The minimum duration for assessing seizure freedom should be the entire stable
      dose period in short-term trials and at least six months for long-term follow-up
      studies. It is proposed that the seizure freedom rates be calculated and reported
      with at least two different methodologies, one that considers patients
      withdrawing from treatment without having had a seizure as successes, and one
      that considers the same patients as failures. For an effective and well-tolerated
      AED, seizure freedom rates will be consistent across the two methodologies.
      CONCLUSIONS: Seizure freedom is the ultimate goal of AED therapy and should be
      reported for all clinical trials. Methodological differences among the few
      clinical studies reporting seizure freedom rates make it difficult to compare
      results across trials. Improved reporting of methodologies and seizure-free rates
      is warranted.

PMID- 16793574
TI  - The origin of the focal spike in musicogenic epilepsy.
AB  - To clarify the pathogenesis of a typical case of musicogenic epilepsy, we
      examined interictal spikes using the dipole tracing method (DTM). The patient was
      a 49-year-old, right-handed Japanese man. He first experienced seizures at the
      age of 32 years; listening to his favorite piece of music frequently triggered
      them. His seizure type is partial (often complex, but sometimes simple). An
      interictal EEG examination revealed many focal spikes in F8 and T4. We estimated
      equivalent current dipoles (ECDs) using DTM. We performed one-dipole analyses on
      the peaks of the spikes using an EEG analyzer with a three-layer head model
      called the scalp-skull-brain (SSB) model. We analyzed the interictal EEG because
      there were no spikes during the seizure. The ECDs were located in the posterior
      transverse temporal gyrus. The characteristics in this patient not only bolstered
      arguments in favor of the role of the right temporal lobe in musicogenic
      epilepsy, but also showed that transverse temporal gyri, which are included in
      the auditory area, could play an important role in musicogenic epilepsy.

PMID- 16793575
TI  - The effect of valproate on silent period and corticomotor excitability.
AB  - OBJECTIVE: To investigate, by transcranial magnetic stimulation, the effects of
      valproate on silent period and corticomotor excitability. METHODS: thirty
      patients with generalized epilepsy were studied at baseline, and re-examined 4
      (S1) and 25 (S2) weeks after the administration of valproate (mean dose: 1040 +/-
      284 mg). Transcranial magnetic stimulation was performed with a figure of eight
      coil (recording, first dorsal interosseous). Threshold was measured at 1% steps.
      Silent period was measured using a recently described protocol. Briefly, silent
      periods were elicited at 5% increments from 0 to 100% maximum stimulus intensity.
      At each stimulus intensity, 4 silent periods were obtained and the average value
      of silent period duration was used to construct a stimulus/response curve of
      stimulus intensity versus silent period. The resulting curves were then fitted to
      a Boltzman function and were statistically compared. The motor-evoked potential
      recruitment curve was constructed under active conditions and analyzed in a
      similar way. RESULTS: Valproate increased threshold from 36.5 +/- 5.99% at
      baseline to 41.02 +/- 7.84% at S1 (p < 0.0001, paired t-test). The maximum value
      of the silent period curve decreased from 257.5 +/- 3.9 ms at baseline to 230.3
      +/- 3.9 ms at S1 (p < 0.0001, F-test and AIC) while the other best-fit values
      (V(50), slope, threshold) were not significantly affected. Regarding the motor
      evoked potential recruitment curve, the maximum value decreased significantly
      post-drug (from 0.449 +/- 0.007 to 0.392 +/- 0.009, p < 0.01, F-test and AIC
      test), whereas the rest of the best-fit values remained unaffected. CONCLUSION:
      In patients with idiopathic generalized epilepsy, valproate increases threshold
      and reduces the maximum values of the silent period curve and the motor-evoked
      potential recruitment curve. These findings probably reflect valproate's effects
      on voltage-dependent Na(+) channels, as well as an activation of GABA(A)
      receptors.

PMID- 16793576
TI  - Stimulus-sensitive burst-spiking in burst-suppression in children: implications
      for management of refractory status epilepticus.
AB  - Status epilepticus refractory to sequential trials of multiple medication is a
      rare but significant problem in children. We describe stimulus sensitivity
      arising during the treatment of convulsive status epilepticus in children
      (stimulus-sensitive burst-spiking in burst-suppression). We reviewed
      retrospectively clinical and EEG features in six children (three months to ten
      years), with status epilepticus requiring intensive care, in whom tactile,
      auditory and visual stimulation induced myoclonic jerks and bursts of EEG spikes.
      Sensitivity was not present at onset, but appeared after 24 hours as myoclonic
      jerks of the eyes, face and limbs, irrespective of the modality and site of
      stimulation. These were associated with burst-suppression in the EEG, the induced
      spiking forming the burst component. Various antiepileptic drugs, including
      GABAergic and NMDA blockers had no effect, but halogenated agents (used in two
      patients) abolished the sensitivity. Two children died, but the remainder
      returned to their previous clinical state. We conclude that stimulus sensitivity
      may appear in the context of refractory status epilepticus treated with high-dose
      barbiturates. Outcome may be more favorable than previously reported in adults,
      mostly in the context of post-anoxic or toxic coma. Evaluation of ventilated
      children in status epilepticus should include electroclinical assessment using
      sensory stimulation. If present, the drug regime should be reviewed and
      halogenated agents considered.

PMID- 16793577
TI  - Ketogenic diet in patients with myoclonic-astatic epilepsy.
AB  - For more than 80 years, the ketogenic diet has been used as an alternative to
      antiepileptic drugs for patients with refractory epilepsy. Myoclonic-astatic
      epilepsy in early childhood is one of the malignant epilepsy syndromes that often
      proves refractory to antiepileptic drugs treatment. Objective. In this
      prospective study we assess the efficacy and tolerability of the ketogenic diet
      in patients with myoclonic-astatic epilepsy. Material and methods. Between March
      1, 1990 and August 31, 2004, 30 patients who met diagnostic criteria of myoclonic
      astatic epilepsy were seen at our department. Eleven of them were placed on the
      ketogenic diet using the Hopkins protocol and were followed for a minimum of 18
      months. Results. The children had previously received a mean of 5.2 different
      antiepileptic drugs and were on a mean of 2.2 antiepileptic drugs when the diet
      was started. Eighteen months after initiating the diet, six of the patients
      (54.5%) remained on the diet. Two patients (18%) were seizure-free, two (18%) had
      a 75-99% decrease in seizures, and the remaining two children (18%) had a 50% to
      74% decrease in seizures. The first two patients were tapered off the diet after
      remaining seizure-free, without antiepileptic drugs for several years. In the two
      patients who had sporadic seizures, antiepileptic drugs were reduced to one, and
      in the last two the seizure frequency was significantly reduced. No differences
      in seizure control were found when compared for age, sex, or seizure type. Five
      of our patients discontinued the ketogenic diet in less than 3 months (four
      because of lack of effectiveness and one because of persistent vomiting).
      Conclusion. The ketogenic diet is a promising therapy for patients with myoclonic
      astatic epilepsy, with over half the children showing a > 50% reduction in
      seizures, and seizure-freedom in 18%. In drug resistant cases of myoclonic
      astatic epilepsy, the diet should be considered early in the course of this
      syndrome and not as a last resort.

PMID- 16793578
TI  - Non-epileptic clinical diagnoses in children referred for an outpatient EEG using
      video monitoring.
AB  - Simultaneous video (closed circuit television [CCTV]) and EEG recordings are
      important in the differentiation of epileptic and non-epileptic paroxysmal
      episodes and in the classification of epilepsy syndromes. An additional benefit
      from the observation of the child on CCTV is the possible identification of
      specific clinical, including genetic, conditions. This three-year prospective
      study of 2780 consecutive children undergoing routine EEG investigations
      identified 17 conditions that had not previously been diagnosed by the clinicians
      who had requested the EEG.

PMID- 16793579
TI  - Are epilepsy classifications based on epileptic syndromes and seizure types
      outdated?

PMID- 16793580
TI  - The non-neurologists' view on epilepsy syndromes classification.

PMID- 16793581
TI  - Epilepsy syndromes still survive.

PMID- 16793582
TI  - Seizures, syndromes and classifications.

PMID- 16793583
TI  - Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB
      activation.
AB  - OBJECTIVE: To study the role of dopamine receptors in the regulation of the
      activity of transcription factor cAMP response element-binding protein (CREB)
      after cocaine treatment. METHODS: By using dopamine receptor antagonists SCH23390
      and nafadotride, the activation of CREB by D1 and D3 dopamine receptors after
      cocaine treatment and role of extracellular signal-regulated kinase (ERK) in
      cocaine-induced CREB activation were examined by Western blotting, which was also
      employed for determination of the effect of SCH23390 and nafadotride on CREB
      activation. RESULTS: D1 receptor antagonist could inhibit cocaine-induced CREB
      activation, while D3 receptor antagonist enhanced cocaine-induced CREB
      activation. Dopamine receptor antagonists SCH23390 and nafadotride did not induce
      CREB activation. SL327, a MEK inhibitor, inhibited cocaine-induced CREB
      activation. CONCLUSION: D1 and D3 dopamine receptors can oppositely regulate CREB
      activation after cocaine treatment and this regulation depends on ERK signaling
      pathway.

PMID- 16793584
TI  - [Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels].
AB  - OBJECTIVE: To explore the effect of intestinal ischemia/reperfusion (I/R) injury
      on leptin and orexin-A levels in peripheral blood and central secretory tissues,
      and investigate the roles of leptin and orexin-A in acute inflammatory responses.
      METHODS: An intestinal I/R injury rat model was established, and the rats were
      grouped according to duration of the reperfusion time following a 60-min
      ischemia. Radioimmunoassay was used to examine the protein levels of leptin in
      the serum and adipose tissue, and the protein levels of orexin-A in the plasma
      and hypothalamus. Reverse transcriptase-polymerase chain reaction was also
      performed to detect the mRNA expressions of adipose leptin and hypothalamus
      orexin-A. RESULTS: Compared with that before injury, serum leptin level of 60-min
      ischemia with 30-min reperfusion (I60'R30') group decreased significantly and
      that of I60'R360' increased significantly. Compared with the sham-operation group
      (sham) after injury, serum leptin level of I60'R360' group increased
      significantly, and adipose leptin protein levels of I60'R30' and I60'R90' groups
      decreased significantly, whereas that of I60'R360' group increased obviously.
      Compared with sham group after injury, adipose leptin mRNA expressions of
      I60'R30', I60'R240' and I60'R360' groups all increased significantly, while that
      of I60'R150' showed significant decrease. No significant changes were noted in
      the protein levels of orexin-A either in the plasma or hypothalamus after I/R
      injury. In comparison with sham group after injury, hypothalamus orexin-A mRNA
      expressions of I60'R30' and I60'R90' groups showed gradual but significant
      decrease, and till 150 min of reperfusion, the expression reached its lowest,
      followed then by slow recovery at 240 and 360 min, though still remaining
      significantly lower than that of sham group. CONCLUSION: Leptin and orexin-A have
      a time-dependent response to intestinal I/R injury, but the former appears to
      exhibit a faster response, and they may play a certain role in the metabolic
      disorders of acute inflammation.

PMID- 16793585
TI  - [Stable expression of HBV C gene mutants in immortalized human B-cell lines].
AB  - OBJECTIVE: To provide an cell model of immortalized lymphoblstoid B-cell lines
      for studying the biological characteristics of full-length hepatitis B virus
      (HBV) genome carrying the hot-spot mutations V60, G87, and L97. METHODS: V60,
      G87, and L97 mutation points were introduced into HBV p3.8 II plasmid containing
      1.2 copy of HBV genome by means of site-directed mutagenesis. The HBV genome was
      amplified by PCR from p3.8 II and p3.8 II-V60, G87, L97 plasmid, and the PCR
      product was inserted into EBO-plpp eukaryotic expression vector. The recombinant
      vectors and the EBO-plpp vector were transfected into immortalized human
      lymphoblasts with lipofectamine 2000 and selected with hygromycin. Steady
      expression of the target genes was determined by RT-PCR, Western blotting and
      microparticle enzyme immunoassay. RESULTS: DNA sequence analysis indicated that
      the desired mutation was introduced into wild-type HBV DNA. HBsAg, HBeAg and
      HBcAg could be detected in EBO-HBV-transfected cell lysate or culture
      supernatant. CONCLUSION: Transfectants that stably express HBV mutant antigen may
      provide a cell model to study the biological characteristics of HBV carrying hot
      spot mutation in vitro.

PMID- 16793587
TI  - [Preliminary study of gene expression profiling in human type I and II
      endometrial carcinoma].
AB  - OBJECTIVE: To study gene expression profiling in human type I and II endometrial
      carcinoma. METHODS: Six Affymetrix human genome genechips were utilized to
      investigate the differences in gene expression profiles between type I and II
      endometrial carcinoma with bioinformatic analysis. RESULTS: Many genes were
      highly expressed in estrogen-dependent endometrial carcinoma, and some of them
      were involved in the metabolism and conversion of estrogen, while some others in
      estrogen regulation. CYP2C9, for instance, was involved in the conversion of
      estrogen sulfate to 16-hydroxy sulfate metabolite, DDC in estrogen-dependent
      pathogenesis of endometrial carcinoma possibly by DDC interaction with AR to
      enhance steroid receptor transcription. CONCLUSION: High expression of these
      genes in estrogen-dependent endometrial carcinoma may provide insights into their
      roles in the pathogenesis and prognosis of this malignancy.

PMID- 16793586
TI  - [Preparation of anti-P21-activated kinase 5 polyclonal antibody and its
      application in dental germ cells].
AB  - OBJECTIVE: To clone PAK5-N terminal sequence for expression in E. coli to prepare
      its polyclonal antibody, and examine the role of PAK5 in dental germ cells.
      METHODS: Based on human PAK5 cDNA sequence, PCR primers were designed to amplify
      PAK5-N terminal sequence. The PCR product was cloned into the expression vector
      pGEX-4T-1 EcoRI/XhoI sites, and the recombinant plasmids were identified by
      agarose gel electrophoresis followed by DNA sequence analysis. The recombinant
      plasmids were transformed into E. coli BL21 and the expression of GST-fusion
      protein was induced by IPTG. Glutathione-Sepharose beads were used to purify GST
      fusion PAK5-N-terminal fragment. Anti-PAK5 polyclonal antibody was obtained in
      immunizing rabbits with purified GST-PAK5 N-terminal fusion protein, and the
      antibodies were purified by protein A beads and used for detection of PAK5
      expression in dental germ cells. RESULTS AND CONCLUSIONS: We successfully cloned
      PAK5-N terminal gene fragment, and achieved protein expression, purification and
      production of PAK5-NT polyclonal antibody. The results of Western blotting
      indicated that PAK5 can be highly expressed in the dental germ cells, suggesting
      that PAK5 may play an important role in biological function of dental germ cells.

PMID- 16793588
TI  - [Impact of PBDE-209 exposure during pregnancy and lactation on immune function of
      offspring rats].
AB  - OBJECTIVE: To assess the potential hazard of environmental deca-brominated
      diphenyl ether (PBDE-209) exposure to the immune function of the offspring rats.
      METHODS: The parental Wistar rats were exposed to PBDE-209 administered
      intragastrically during pregnancy and lactation, and the development of the
      immune organs and changes in T lymphocyte subset and their proliferation, NK cell
      surface markers CD161 and serum immunoglobulins (IgM and IgG) were observed.
      RESULTS: Significant differences in the weight of the immune organs were noted
      between the exposure group and control group. In the exposure group, the
      percentage of T lymphocyte subset CD3(+), CD4(+), CD8(+), CD4(+)CD8(+), the
      percentage of NK cell surface markers CD16 1 and CD4(+)/CD8(+) ratio were
      lowered, while the percentage of CD4(-)CD8(-) cells increased. T lymphocyte
      subset proliferation in the exposure group did not show obviously changes, but
      compared with the control group, the IgM level in the exposure group was
      significantly lowered. No significant differences were observed in IgG levels
      between the exposure and control groups. CONCLUSION: Continuous exposure to high
      dose PBDE-209 in female rats during pregnancy and lactation results in possible
      adverse effect on the immune function of the offspring rats.

PMID- 16793589
TI  - [Effect of cell surface sialic acid and their linkages on adhesion of mammary
      carcinoma cells].
AB  - OBJECTIVE: To investigate the effect of cell surface sialic acid and its linkage
      on the cell-cell and cell-matrix adhesion of mammary carcinoma cells MD-MB-435.
      METHODS: MD-MB-435 cells were sense-transfected with ST6Gal I cDNA or antisense
      transfected with part of the ST6Gal I sequence inserted in pcDNA 3.1 vector, with
      mock transfection with pcDNA3.1 vector as the control. The cell surface alpha2, 6
      linked sialylation was determined by fluorescence-activated cell sorting (FACS)
      using lectin SNA (Sambucus nigra agglutinin specific to alpha2, 6-linked sialic
      acid on N-linked glycoprotein). A significantly increased alpha2, 6-sialylation
      subclone in sense-transfectants and a decreased alpha2, 6-sialylation subclone in
      antisense-transfectants were selected for further examination of cell-cell and
      cell-matrix (collagen IV) adhesion. The transfectants were also treated with
      sialidase to compare the capacity of cell adhesion affected by cell surface
      sialylation. RESULTS: Sense-transfection subclone showed a reduced cell-cell
      aggregation but enhanced cell-matrix adhesion. In contrast, the antisense
      transfection subclone exhibited increased cell-cell aggregation and decreased
      cell-matrix adhesion. After treatment with sialidase, the cell-matrix adhesion of
      all the transfectants and the parental MDA-MB-435 cells were significantly
      reduced to the level of 31%-57% of untreated cells. CONCLUSION: Cell surface
      sialic acid and alpha2, 6-linked sialylation play an important role in cell-cell
      and cell-matrix adhesion of mammary carcinoma cell MDA-MB-435.

PMID- 16793590
TI  - [Modification of the method for preparing rabbit liver VX2 tumor model and its
      MRI findings].
AB  - OBJECTIVE: To improve the method for preparing rabbit VX2 liver tumor model and
      observe the magnetic resonance imaging (MRI) features of the implanted tumors.
      METHODS: Sixteen adult New Zealand white rabbits were assigned randomly into 4
      equal groups, and VX2 tumor tissues were implanted into the right and left liver
      lobes with spiral CT guidance. Plain and contrast-enhanced MR scan and
      pathological analysis were performed in different stages (14, 18, 22 and 26 days)
      after tumor implantation. RESULTS: Tumor implantation was successful in all the
      rabbits, and 18 to 22 days after tumor implantation, the diameters of the tumor
      ranged from 1 to 2 cm, which allowed observation and study. In plain MR scans,
      lower or equivalent tumor signal in comparison with hepatic parenchyma was
      observed, and contrast-enhanced scans produced obvious enhancement of the tumor
      edges. At 22 days after tumor implantation, obvious necrosis was observed in the
      center of the tumor. CONCLUSION: This method of preparing rabbit VX2 liver tumor
      model with spiral CT guidance is simple and convenient, and the tumors can be
      observed effectively with dynamic plain and contrast-enhanced MR scans.

PMID- 16793591
TI  - [Construction of fusion expression vector EGFP-PDX-1 and its transfection into
      rat fetal hepatic stem cells by electroporation].
AB  - OBJECTIVE: To construct the fusion expression vector of pancreatic-duodenal
      homeobox gene 1 (PDX-1) fused to green fluorescent protein (GFP) capable of
      stable expression in fetal rat hepatic stem cells after transfection by
      electroporation. METHODS: PDX-1 cDNA was amplified from SK900/BLSCRIPT plasmid
      and cloned into the multiple cloning site of pEGFP-C1 to obtain the recombined
      plasmid pEGFP-C1-PDX-1. Rat fetal hepatic stem cells were isolated, cultured,
      identified and transfected with the recombinant vector by electroporation,
      followed by observation of these cells with fluorescent microscope. The result of
      transfection was analyzed by RT-PCR and cell growth curve. RESULTS:
      Identification by enzyme digestion confirmed successful construction of the
      recombinant vector. Fetal hepatic stem cells can stably express GFP and PDX-1 for
      a period of time, and their growth and proliferation was not obviously affected
      after transfection. CONCLUSION: The fusion expression vector of EGFP-PDX-1 is
      successfully constructed and stably expressed in rat fetal hepatic stem cells,
      which may facilitate the study of the role of PDX-1 in stem cell differentiation
      into insulin-producing cells.

PMID- 16793592
TI  - [Development of an anti-infection nano-hydroxypatite drug delivery microsphere
      and its drug-release in vitro].
AB  - OBJECTIVE: To develop an anti-infection nano-hydroxypatite (nano-HA) microsphere
      for local drug delivery for treating osteomyelitis. METHODS: The nano-HA was used
      as the core carrier to load gentamicin (GM) and coated with poly(-hydroxybutyrate
      co- hydroxyvalerate)/polyethylene glycol (PHBV/PEG), which was degradable and
      biocompatible, to prepare nano-HA-PHBV/PEG-GM microsphere. The surface structure
      and in vitro drug-release of the microsphere were studied. RESULTS: The
      microsphere had good drug delivery capability. The samples weighing 90 mg each
      were soaked in PBS and gentamicin release within the first day was 165.2
      microg/ml, which maintained a low release rate in the following days. After 28
      days, gentamicin release declined to 8.5 microg/ml, which was higher than the
      minimal inhibitory concentration of gentamicin (2 microg/ml). CONCLUSION: The
      local drug delivery system has good drug-release performance in vitro and may
      possess potential value in clinical management of osteomyelitis.

PMID- 16793593
TI  - [Cloning and sequencing of the junction fragment of dystrophin gene with exons 3
      to 5 deletion].
AB  - OBJECTIVE: To study the mechanisms of dystrophin gene deletion by cloning and
      sequencing the junction fragment of dystrophin gene with exons 3 to 5 deletion.
      METHODS: PCR was performed to verify dystrophin gene exons 3 to 5 deletion in a
      patient with Duchenne muscular dystrophy. A PCR-based genome-walking method was
      used to localize the breakpoint in introns 2 and 5, and the deletion-junction
      fragment was directly amplified by PCR approach with forward and reverse primers
      annealing to a DNA sequence as close as possible to the breakpoint in the introns
      2 and 5. The sequencing result of the deletion-junction fragment was compared
      with the normal intron sequences. RESULTS: A sequence of 2113 bp containing the
      junction fragment was obtained. The 5' breakpoint was located in SINE/Alu element
      of intron 2, and the 3' breakpoint was located in the unique sequence near the
      sequence TTTAAA. The breakpoints were associated with a strong topoisomerase II
      cleavage site. A 26-bp fragment was inserted into the breakpoint and formed 3
      duplications (GGCTTATATTTAA) of 13 bp around the deletion-junction fragment.
      CONCLUSION: Repeat sequence and strong topoisomerase II cleavage site around the
      breakpoint may predispose double-strand DNA breaks and recombination, which, in
      addition to the nonhomologous end-joining mechanism, may contribute as important
      factors to the gene deletion.

PMID- 16793594
TI  - [Effects of motilin agonists on intracellular calcium mobilization in cultured
      rat myenteric neurons].
AB  - OBJECTIVE: To investigate the effects of motilin agonists on intracellular Ca(2+)
      mobilization in primary cultured rat myenteric neurons. METHODS: Motilin-induced
      and erythromycin-induced intracellular Ca(2+) signaling was studied in primary
      cultures of rat myenteric neurons using the radiometric Ca(2+) indicator Furo3/AM
      with a laser confocal microscope. RESULTS: In Hank's solution, 10(-8), 10(-7),
      and 10(-6) mol/L motilin could elevate intracellular Ca(2+) concentration
      ([Ca(2+)]i) to the peak levels of 10.6-/+2.1, 15.9-/+1.2, and 30.6-/+3.7
      respectively with their relative percentage change in fluorescent intensity of
      (40.1-/+6.3)%, (63.0-/+11.2)%, and (100.8-/+18.4)% respectively, indicating the
      dose-dependent effect of motilin on [Ca(2+)]i. In Hank's solution, 10 microg/ml
      erythromycin could induce the elevation of [Ca(2+)]i to the average peak of 23.2
      /+5.6 with the relative percentage change in fluorescent intensity of (82.8
      /+13.0)%. When pretreated with the antibody against motilin receptor in Hank's
      solution, the effect of 10 microg/ml erythromycin was almost inhibited
      completely. CONCLUSION: Motilin can increase [Ca(2+)]i, and erythromycin also has
      this effect by binding to motilin receptor.

PMID- 16793595
TI  - [A fast approach for level set segmentation].
AB  - To propose an optimal level set approach for fast medical image segmentation. By
      confining the computation quantity of the level sets function and using the image
      characteristics, we improved the efficiency of segmentation and decreased the
      parameter setting in some degree for DSA vascular segmentation.

PMID- 16793596
TI  - [Morphological characteristics of internal carotid artery atherosclerotic lesions
      in digital subtracted angiography].
AB  - OBJECTIVE: To illustrate the morphological characteristics of atherosclerotic
      lesions of the internal carotid artery. METHODS: The morphological
      characteristics of cervicocerebral atherosclerotic lesions in digital subtracted
      angiography were retrospectively reviewed in 120 cases. RESULTS: Totally 217
      atherosclerotic lesions were detected. Of all the lesions, moderately and
      severely stenosed lesions accounted for 62.21% and mild stenosed lesions for
      37.79%; long lesions were found in 18.89% and short ones in 81.11%; 37.33% of the
      lesions were ulcerated while 62.67% were non-ulcerated; 13.36% were angulated
      lesions and 86.64% non-angulated; 50.23% were eccentric lesions and 49.77% were
      concentric; lesions with adjacent artery dilation were found in 9.22%, and
      lesions without with adjacent artery dilation in 90.78%. CONCLUSION: The
      atherosclerotic lesions are characterized by moderate to severe stenosis and non
      ulcerated, non-angulated, eccentric lesions without adjacent artery dilation.

PMID- 16793597
TI  - [Long-term observation of large weight-bearing bone defect in goats repaired with
      tissue engineering technique].
AB  - OBJECTIVE: To observe the long-term effect of tissue engineering-based repair of
      large weight-bearing bone defect in goats, and the final outcome of the scaffold
      material coral hydroxyapatite (CHAP) in vivo. METHODS: Fifteen Chinese goats were
      subjected to operations to induce a 2-cm left tibial diaphyseal defect, which was
      filled subsequently with CHAP and bone marrow stromal stem cells (BMSCs). The
      repaired defects were evaluated by ECT, X-ray and histology in the early stage
      and at 6, 12, 18, and 24 months postoperatively. RESULTS: ECT showed good bone
      regeneration and revascularization within 2 months postoperatively. X-ray and
      histology displayed eccentric and gradual bone regeneration in the early stage,
      and the tissue-engineered bone graft was firmly healed with the goat tibia. X-ray
      and histological examination at 6, 12, 18, 24 months postoperatively revealed
      moulding of the new bones and medullary cavity recanalization, and the structure
      of CHAP disappeared and gradually integrated into the new bones. CONCLUSION:
      Tissue-engineered bone is capable of total repair of large bone defect in goats
      by forming normal functional new bones. CHAP can be eventually degraded
      completely and become the component of the newly generated bones.

PMID- 16793599
TI  - [Nestin activation after rat cerebral ischemia-reperfusion injury and its changes
      in response to Tongxinluo treatment].
AB  - OBJECTIVE: To investigate nestin activation in rat brain subjected to ischemia
      reperfusion injury and its changes in response to Tongxinluo treatment. METHODS:
      Cerebral ischemia was induced by temporary middle cerebral artery occlusion
      (MCAO) in rats. At 3, 7, 14 and 21 days after MCAO, nestin expression in the
      ependyma, subventricular zone (SVZ), hippocampal subdentate gyrus zone (HDG) of
      the rats treated with Tongxinluo were guantified by immunohistochemistry.
      RESULTS: Compared with the sham operation group, nestin was significantly
      increased 7, 14 and 21 days after MCAO (P<0.05), and immunofluorescence of
      BrdU+nestin-positive neurons significantly increased in the SVZ. After treatment
      with Tongxinluo, the number of BrdU-positive neurons and BrdU+nestin-positive
      neurons significantly increased as compared with MCAO group (P<0.05). CONCLUSION:
      Focal cerebral ischemia in the rat results in rapid response and proliferation of
      neural stem cells in the SVZ and HDG in the ischemic hemisphere, and Tongxinluo
      may enhance the differentiation and proliferation capacity of the neural stem
      cells after MCAO.

PMID- 16793598
TI  - [Effects of the HLA antibodies on allograft acute rejection after cadaveric liver
      transplantation].
AB  - OBJECTIVE: To evaluate the effect of perioperative HLA antibody changes on acute
      allograft rejection in cadaveric liver transplantation. METHODS: Totally 134
      patients received modified piggyback liver transplantation and enzyme-linked
      immunosorbent assay was performed for HLA antibody detection before and the 1, 7,
      14 and 30 days after operation. B ultrasound-guided liver biopsy was employed for
      diagnosis of acute allograft rejection, and the perioperative changes of HLA
      antibodies were evaluated for their effect on allograft acute rejection. RESULTS:
      Of the 44 recipients with preoperative positivity for HLA antibodies, acute
      rejection occurred in 56.8% of the patients, as compared with 25.9% in those
      negative for HLA antibody (P=0.001). The patients who became positive for HLA
      antibody postoperatively had a rate of acute rejection of 60%, which was
      significantly higher than that in those persistently negative for HLA antibody
      (18.6%, P=0.003). CONCLUSION: HLA antibody positivity before transplantation may
      contribute to acute rejection episode in liver transplantation, and persistent
      posttransplant HLA antibody positivity is closely associated with the occurrence
      of acute rejection.

PMID- 16793600
TI  - [Ganoderma polysaccharides antagonize prostaglandin E2-induced suppression of
      murine splenocyte IFN-gamma and TNF-alpha mRNA expression].
AB  - OBJECTIVE: To determine if Ganoderma polysaccharides can antagonize prostaglandin
      E2 (PGE2)-induced suppression of murine splenocyte interferongamma (IFN-gamma)
      and tumor necrosis factor alpha (TNF-alpha) mRNA expression. METHODS: Mixed
      lymphocyte culture reaction was used as the experimental model. The expressions
      levels of IFN-gamma and TNF-alpha mRNA were measured by semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR). RESULTS: After the cultures
      were treated with PGE2 for 4 h, IFN-gamma mRNA expression was reduced as compared
      with the control, which was especially obvious when PGE2 concentrations exceeded
      10 micromol/L (P<0.01). Ganoderma polysaccharides above 100 mg/L showed partial
      antagonistic effect against the inhibition of IFN-gamma by PGE2 at the fixed
      concentration of 20 micromol/L. Further studies indicated that PGE2 (20
      micromol/L) impaired the expression of TNF-alpha mRNA after an 8-hour incubation
      and Ganoderma polysaccharides above 100 mg/L could partially antagonize this
      effect. CONCLUSION: Ganoderma polysaccharides can partially antagonize PGE2
      induced suppression of murine splenocyte IFN-gamma and TNF-alpha mRNA expression.

PMID- 16793601
TI  - [Pathological changes of the blood vessels in rabbit femoral head with
      glucocorticoid-induced necrosis].
AB  - OBJECTIVE: To observe the pathological changes in the blood vessels in rabbit
      femoral head with glucocorticoid-induced necrosis and investigate the
      pathogenesis of glucocorticoid-induced osteonecrosis. METHODS: Twenty New Zealand
      white rabbits were randomly divided into two groups, namely group A. which was
      injected with horse serum and prednisone and group B as the control group.
      Chinese ink was injected into the femoral cavity of the rabbits to observe the
      blood vessels in the femoral head under optical microscope and the femoral head
      was examined histopathologically. RESULTS: Compared with the normal control
      group, the rabbits in group A had significantly decreased number of perfused
      vessels, which was featured by defective perfusion, osteocytie pyknosis or
      necrosis, increase of empty ostoocyte lacunae and fat cells, decrease of
      hematopoietic tissue, and blood vessel occlusion. CONCLUSION: Vascular occlusion
      and vasculitis due to glucocorticoid treatment may cause avascular necrosis of
      the femoral head.

PMID- 16793602
TI  - [Determination of octafluoropropane content in human albumin micropheres loaded
      with octafluoropropane].
AB  - OBJECTIVE: To develop a method for determinating the octafluoropropane (OFP)
      content in human albumin micropheres loaded with OFP. METHODS: OFP content in the
      loaded human albumin micropheres was determined by means of gas chromatography
      coupled with mass spetrum/selected ion monitoring (GC-MS/SIM). RESULTS: The
      calibration curve was linear within the concentration range of 40.92-16,368
      nmol/L (R(2)=0.9999). The limit of detection was 8.18 nmol/L, and the recovery
      rate was (100.98-/+1.4)% (204 nmol/L), (102.63-/+2.29)% (2,046 nmol/L) and (97.5
      /+2.2)% (8,184 nmol/L), respectively. The intra-day and inter-day RSDs were 0.6%
      2.0% and 0.86%-2.3%, respectively. CONCLUSION: The method of GC-MS/SIM is
      accurate, sensitive, precise and applicable for OFP determination in the
      microspheres.

PMID- 16793603
TI  - [Correlation between pressure-derived coronary collateral flow and Rentrop grade
      after primary percutaneous intervention of acute myocardial infarction].
AB  - OBJECTIVE: To analyze the correlation between pressure-derived collateral
      coronary flow (PDCF) and Rentrop grade of patients with acute myocardial
      infarction (AMI). METHODS: PDCF, determined by the ratio of P(w)/P(a), was
      measured in 29 patients with AMI of the first onset who received primary
      percutaneous coronary intervention (PCI) within 12 h after the onset. Sufficient
      collateral flow (group A, n=19) was defined as PDCF>0.24 and insufficient
      collateral flow (group B, n=10) as PDCF< or =0.24. Rentrop grade of the
      collateral flow was evaluated by coronary angiography. Echocardiography was
      performed on the 3rd and 30th day after PCI. The left ventricular ejection
      fraction, end-systolic and end-diastolic volumes, and the related indexes were
      obtained. RESULT: Rentrop grade was significantly related to PDCF (r=0.75,
      P<0.01), but a wide range of PDCF was observed in patients with Rentrop grade< or
      =1. CONCLUSION: PDCF measurement allows quantitative evaluation of the collateral
      flow in patients with AMI.

PMID- 16793604
TI  - [Effects of subanesthetic dose of ketamine on perioperative serum cytokines in
      orthotopic liver transplantation].
AB  - OBJECTIVE: To evaluate the effects of ketamine on perioperative serum cytokine
      levels in patients undergoing orthotopic liver transplantation (OLT). METHODS:
      Twenty patients undergoing OLT were randomly divided into ketamine group (n=10)
      and control group (n=10). Patients in ketamine group were given intravenous bolus
      injection of ketamine at 0.25 mg/kg followed by ketamine infusion at 0.5 mg.kg(
      1).h(-1) until the end of operation except in the anhepatic phase, whereas the
      control group received saline of the same amount. Arterial blood samples were
      obtained at the start of surgery (T(1)), 5 min before the anhepatic phase (T(2)),
      5 min before recirculation (T(3)), 15 and 60 min after recirculation (T(4),
      T(5)), and 0, 4 and 24 h after operation (T(6), T(7), T(8)). Serum levels of
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 were
      measured by ELISA. RESULTS: Serum TNF-alpha, IL-6 and IL-10 levels increased
      significantly during anhepatic phase as compared with the baseline level (T(1))
      (P<0.05), and the changes were especially obvious in IL-6 and IL-10. The levels
      of the cytokines kept rising after recirculation and reached the peak level at
      T(5)(P<0.05), followed then by rapid decline and still maintaining higher levels
      than the preoperative ones 24 h after operation. The levels of TNF-alpha in
      ketamine group between T(2) and T(7) were significantly lower than that in the
      control group, and the IL-6 level between T(2) and T(5) were also significantly
      lower in ketamine group. Serum IL-10 level did not show any significant
      difference between the two groups. CONCLUSION: Ischemia and reperfusion injury of
      the liver and surgical stress induce pro- and anti-inflammatory cytokine
      responses during liver transplantation, in which event IL-6 and IL-10 are more
      sensitive than TNF-alpha. Ketamine can inhibit the production of TNF-alpha and IL
      6 but not IL-10.

PMID- 16793605
TI  - [Expression of TFAR19(PDCD5) in normal human kidney, renal clear cell carcinoma,
      normal human bladder and bladder carcinoma].
AB  - OBJECTIVE: To detect the expression of apoptosis gene PDCD5 in tissues of normal
      human kidney, renal clear cell carcinoma, normal bladder and bladder carcinoma,
      and explore the role of PDCD5 gene in renal clear cell carcinoma and bladder
      carcinoma. METHODS: Indirect immunohistochemistry was employed to detect PDCD5
      expression in 63 kidney specimens and 42 bladder specimens. Positive expression
      rates and intensity of PDCD5 protein expression in the kidney tissue were
      investigated microscopically and by computerized image analysis. Positive
      expression rate in the bladder tissue was investigated by microscopic
      observation. RESULTS: The results of immunohistochemical staining showed PDCD5
      protein overexpression in the renal tubule of normal human kidney tissues and
      downregulation with the stage increase of renal clear cell carcinoma. PDCD5
      protein expression showed statistical significance in tissues of normal kidney
      and renal clear cell carcinoma in all stages. No obvious PDCD5 expression was
      detected in the tissues of normal human bladder and bladder carcinoma.
      CONCLUSION: PDCD5 is an important apoptosis-regulating factor in the occurrence
      of renal clear cell carcinoma, and its expression is extremely low in tissues of
      normal human bladder and bladder carcinoma.

PMID- 16793606
TI  - [Role of TJU103 in prevention of graft-versus-host disease after allogeneic stem
      cell transplantation in mice].
AB  - OBJECTIVE: To explore the role of TJU103 in preventing graft-versus-host disease
      (GVHD) after allogeneic stem cell transplantation in mice. METHODS: BALB/c mouse
      splenic lymphocytes were collected and treated by mitomycin as the activating
      cells and the C57BL/6 mouse splenic lymphocytes as the reacting cells. In the
      experimental groups, the effect of TJU103 on the proliferative response of T
      cells was observed. BALB/c(H-2d) and CB6F1(H-2d/b) mice were used as the MHC-full
      mismatched recipients and MHC-haplo-identical recipients, respectively, and
      pretreated by total body irradiation at 9.0 Gy before transplantation. For the
      recipients of the irradiation group, 0.3 ml D-Hank's solution was injected
      through the tail vein without cell transplantation, the recipients of the control
      group received injection of 4.5x10(6) bone marrow cells mixed with 3.0x10(7)
      spleen cells from C57BL/6 mice through the tail vein, and those in the
      experimental group received cell transplantation in the same manner with also
      injection via the tail vein of 25 microg/ml TJU103, which was subsequently
      injected intraperitoneally for 7 consecutive days at daily dose of 50 microg. The
      hematopoietic recovery, engraftment and GVHD of the recipients were observed.
      RESULTS: TJU103 resulted in a dose-dependent inhibition of T cell proliferation
      in mixed lymphocyte reaction (MLR), and nearly 83% inhibition of the
      proliferative response was observed with the addition of 25 microg/ml of TJU103.
      Without any treatment, the occurrence of GVHD and death rate in the control group
      was both 10/10. Daily injection of TJU103 at 50 microg for the initial post
      transplantation week protected the mice from GVHD. In the MHC-full-mismatched
      model, the incidence of GVHD and survival rate on day 30 of the experiment group
      was 2/10 and 8/10, showing significant difference from those in the control group
      (P<0.01). The median survival time (MST) was 30 days in the experimental group
      versus 15 days in the control group (P<0.05). In the MHC-haplo-identical model,
      the incidence of GVHD and the survival rate on day 30 of the experimental group
      was 1/10 and 9/10, which were significantly different from the control group
      (P<0.01). The MST was 30 days in the experimental group versus 14 days in the
      control group (P<0.05). CONCLUSION: TJU103 is capable of markedly inhibiting T
      cell proliferative response in vitro and can decrease GVHD incidence after
      allogeneic stem cell transplantation in mice.

PMID- 16793607
TI  - [Diclofenac suppresses hepatoma cell proliferation and promotes cyclooxygenase-2
      mRNA expression].
AB  - OBJECTIVE: To investigate the effects of cyclooxygenase inhibitor diclofenac on
      the proliferation and cyclooxygenase-2 (COX-2) mRNA expression of cultured
      hepatocellular carcinoma cell lines HepG2, Hep3B and human hepatocellular cell
      line QSG-7701. METHODS: After exposure to diclofenac at various concentrations
      (10-200 micromol/L) for 24, 48 and 72 h, the cell proliferation was analyzed by
      Cell Counting Kit-8 (CCK-8) assay and mRNA expression determined by semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      Diclofenac exposure for 24, 48 and 72 h significantly inhibited HepG2 and Hep3B
      cell proliferation in a concentration-dependent manner, with inhibition rate of
      40.47% and 54.49% after 48 h exposure to 50 micromol/L diclofenac and IC50 of
      70.54 and 48.39 micromol/L, respectively. A much weaker antiproliferative effect
      on QSG-7701 cells was shown, with IC50 of 189.91 micromol/L after 48-hour
      exposure to diclofenac. RT-PCR detected COX-2 mRNA in HepG2 and Hep3B cells, but
      hardly in QSG-7701 cells. Treatment with diclofenac or 5-Fu resulted in elevated
      COX-2 mRNA expression both in HepG2 and Hep3B cells. CONCLUSION: Diclofenac can
      specifically inhibit the proliferation of COX-2-expressing HepG2 and Hep3B cells,
      and induce up-regulation of COX-2 mRNA expression, which indicates the important
      role of COX-2 in the proliferation of hepatoma cells.

PMID- 16793608
TI  - [Preparation and functional identification of testicular Sertoli cells].
AB  - OBJECTIVE: To simplify the method for separation and cultivation of rat
      testicular Sertoli cells with high viability, quantity and expression efficiency.
      METHODS: Testicular Sertoli cells from 2 to 3-week-old male Wistar rats were
      prepared by digestion with collagenase, trypsin and DNase and cultured together
      with active lymphocytes to observe their killing effect against lymphocytes.
      After cell culture for 72 h, the Sertoli cells were morphologically observed by
      different means and identified with transmission electron microscope. Fas ligand
      and follicle-stimulating hormone receptor (FSHR) were examined
      immunohistochemically to identify testicular Sertoli cells. SABC method was used
      for labeling the Fas ligand on the testicular Sertoli cells. RESULTS: The
      viability of the isolated and cultured Sertoli cells was more than 90%, and in in
      vitro culture, Sertoli cells, which expressed the Fas ligand, could kill the
      active lymphocytes. CONCLUSION: This method improves the efficiency in
      acquisition of rat testicular Sertoli cells expressing Fas ligand, which are
      believed to be a potential donor for co-transplantation with parathyroid cells to
      offer immune privilege.

PMID- 16793609
TI  - [Expressions of h-TERT, c-myc, PCNA and cell apoptosis in liver carcinogenesis].
AB  - OBJECTIVE: To investigate the expressions of human telomerase reverse
      transcriptase (h-TERT), c-myc, and proliferating cell nuclear antigen (PCNA) in
      chronic viral hepatitis (CVH), liver cirrhosis and primary hepatocellular
      carcinoma (HCC) and understand their possible role in liver carcinogenesis.
      METHODS: Totally 157 liver disease specimens were collected, including 56 CVH, 52
      liver cirrhosis and 49 primary HCC specimens. In situ hybridization was performed
      on these specimens to examine the expressions of h-TRET and c-myc mRNA, and
      immunohistochemistry carried out for PCNA detection, with the cell apoptosis
      detected with in situ ending labeling. RESULTS: In the CVH, liver cirrhosis and
      primary HCC specimens, h-TERT expression was detected at the frequencies of 11/56
      (19.6%), 43/52 (82.7%) and 44/47 (93.6%), c-myc expression at 7/56 (12.5%), 21/52
      (40.4%) and 26/47 (55.3%), with apoptotic index of (27.3-/+4.7)%, (16.5-/+2.6)%
      and (8.7-/+1.3)% and PCNA expression rate of (17.1-/+2.9)%, (49.3-/+7.8)% and
      (62.5-/+9.1)%, respectively. Correlations among h-TERT, c-myc, and PCNA
      expressions and the apoptotic index were not found in the examined tissues
      (P>0.05). CONCLUSION: Liver carcinogenesis may involve increased h-TERT, c-myc,
      and PCNA expressions and suppressed cell apoptosis.

PMID- 16793610
TI  - [Oncogene ZNF217 amplification on chromosome 20 q in ovarian serous
      cystadenocarcinoma and its clinical implications].
AB  - OBJECTIVE: To investigate the amplification of zinc finger protein 217 (ZNF217)
      gene on chromosome 20 in ovarian cancer and its clinical significance. METHODS:
      Twenty-three specimens of ovarian carcinoma (11 cases of early stage and 12
      advanced stage), 10 specimens of benign ovarian tumors and 7 normal ovaries were
      examined for ZNF217 gene amplification on chromosome 20 by fluorescence in situ
      hybridization (FISH). RESULTS: ZNF217 gene amplification was detected in 12 cases
      of ovarian cancer (52.17%) and 1 case of benign ovarian tumor, but not in normal
      ovary. ZNF217 amplification was significantly associated with ovarian cancer.
      CONCLUSION: Oncogene ZNF217 is associated with the tumor stage and poor prognosis
      of patients with ovarian cancer.

PMID- 16793611
TI  - [Cloning of A73 gene and its coding sequence analysis].
AB  - OBJECTIVE: To clone A73 gene of Epstein-Barr virus (EBV) and examine the
      variation of its coding sequence. METHODS: A73 coding sequence (CDS) amplified
      from 7 patients in nasophryngeal carcinoma (NPC) biopsies by RT-PCR was cloned
      into pGEM-T-Easy vector to construct the recombinant plasmid, which was subjected
      to sequence analysis in Gen Bank database using Blast software. RESULTS: A73 gene
      from nasophryngeal carcinoma was successfully cloned into pGEM-T Easy vector. A
      locus with conversion of A-->C in A73 was found at CDS 45 nt, located in the
      exonVB157154 nt, which did not result in an amino acid replacement, and the
      variation frequency was 7/7. CONCLUSION: There is a point mutation in A73 CDS of
      EBV isolated from NPC tissue, which might produce NPC-associated polymorphism
      with possible involvement in the composition of some subtype of EB virus.

PMID- 16793612
TI  - [Acute normovolemic hemodilution combined with controlled hypotension in patients
      undergoing liver tumorectomy].
AB  - OBJECTIVE: To evaluate the effects of acute normovolemic hemodilution (ANH)
      combined with controlled hypotension on reducing heterogeneous transfusion and
      safety during liver tumorectomy. METHODS: Thirty patients undergoing elective
      liver tumorectomy were randomly divided into 3 groups (10 each), namely ANH group
      (group A), ANH combined with controlled hypotension group (group B) and control
      group (group C). All the patients were anesthetized via endotracheal intubation.
      Before the operation, ANH was performed in groups A and B after anesthesia
      induction, and controlled hypotension was initiated in group B during
      tumorectomy. Blood transfusion and fluid infusion were carried out routinely in
      group C. Hb and Hct were measured before operation, after ANH, and immediately, 1
      day and 7 days after the operation. The difference in intraoperative blood loss
      and heterogeneous blood transfusion volume in the 3 groups was observed. RESULTS:
      In group A, heterogeneous blood transfusion was avoided in 6 cases and but given
      in the other cases for an average of 400 ml. In group C, every patient received
      heterogeneous blood transfusion (664.8-/+248.1 ml), but none of the patients
      received heterogeneous blood in group B. The difference in transfusion volume
      between the 3 groups was significant (P<0.01). Hemodynamics was basically stable
      during operation in the 3 groups. CONCLUSION: ANH combined with controlled
      hypotension is safe and effective for decreasing and even avoiding homologous
      blood transfusion in liver tumorectomy.

PMID- 16793613
TI  - [Female urogenital mycoplasma infection and drug sensitivity status in Changsha].
AB  - OBJECTIVE: To survey mycoplasma infection in female urogenital tract and analyze
      the drug sensitivity of mycoplasma in Changsha. METHODS: Ureaplasma urealyticum
      (Uu) and Mycoplasma hominis (Mh) were detected in 6566 cases of female urogenital
      tract infection by means of mycoplasma culture and drug sensitivity reagent kit.
      Sensitivity tests for 10 antibiotics were also performed. RESULTS: A total of
      2938 cases were mycoplasma-positive (positivity rate of 44.75%), including 2469
      Uu-positive cases (37.6%), 52 Mh-positive cases (0.08%) and 417 cases positive
      for both Uu and Mh (6.35%). Josamycin, doxycycline, clarithromycin and
      azithromycin were more effective against Uu infection. Josamycin, doxycycline and
      thiamphenicol were more effective against Mh infection. Mixed infection with Uu
      and Mh was more resistant to most antibiotics but Josamycin and doxycycline.
      CONCLUSION: The female urogenital mycoplasma infection results mainly from Uu.
      Compared with simple Uu or Mh infection, mixed infection with Uu and Mh has
      significantly greater resistance to a wider variety of drugs. Josamycin and
      doxycycline are the primary choice for female urogenital mycoplasma infection in
      Changsha.

PMID- 16793614
TI  - [Clinical significance of antineutrophil cytoplasmic antibodies in patients with
      lupus nephritis].
AB  - OBJECTIVE: To analyze the clinical features of patients with lupus nephritis
      positive for antineutrophil cytoplasmic antibodies (ANCA) and explore the
      clinical implications of ANCA detection. METHODS: Totally 261 patients with lupus
      nephritis were enrolled in this study, including 53 ANCA-positive and 208 ANCA
      negative ones. The clinical data of the patients pertaining to the disease
      history, physical examination, laboratory examinations and pathological
      inspection were retrospectively analyzed. RESULTS: Compared with patients
      negative for ANCA, the ANCA-positive patients had significantly higher incidence
      of serositis (75.5%), acute renal failure (64.2%), myocarditis (30.2%),
      neuropsychiatric involvement (26.4%) and lung hemorrhage (7.5%)(P<0.05).
      Significant differences were also found between the two groups in SLE disease
      active index (SLE-DAI), number of the diagnostic criteria, erythrocyte
      sedimentation rate (ESR), anemia, anti-Sm antibodies, and serum complement C(3).
      Most patients positive for ANCA (67.9%) had type IV lupus nephritis with more
      crescent formation, renal tubular atrophy, hyaline thrombi, and higher mortality
      rate as well than the negative patients. CONCLUSION: ANCA detection may benefit
      the estimation of the disease severity and prognostic evaluation of lupus
      nephritis.

PMID- 16793615
TI  - [Screening, isolation and identification of nisin resistance determinant gene in
      strains of Lactococcus lactis].
AB  - OBJECTIVE: To isolate and identify nisin resistance determinant (NSR) gene from
      Lactococcus lactis. METHODS: The Lactococcus lactis strains harboring NSR gene
      were isolated from different milk samples by selective culture supplemented with
      nisin and confirmed by PCR detection of 16S rRNA. Nisin resistance determinant
      gene was determined by PCR amplification, enzyme digestion and sequencing.
      RESULTS: Thirty nisin-resistant Lactococcus lactis strains from fresh milk
      samples were obtained. Three of these strains contained NSR gene of about 1000 bp
      as determined by agarose gel electrophoresis and further confirmed by enzyme
      digestion and sequence analysis. The NSR gene was located on the plasmid of
      Lactococcus lactis. CONCLUSION: Complete NSR gene, located on the bacterial
      plasmid, has been successfully isolated from nisin-resistant Lactococcus lactis
      strains from fresh milk.

PMID- 16793616
TI  - [Dynamic monitoring of serum human chorionic gonadotropin beta-subunit levels for
      early diagnosis of ectopic pregnancy].
AB  - OBJECTIVE: To assess the value of monitoring serum human chorionic gonadotropin
      beta-subunit (beta-HCG) level changes in early diagnosis of ectopic pregnancy.
      METHODS: Totalling 106 cases of ectopic pregnancy and 69 cases of threatened
      abortion were included in the study. Blood samples were collected to examine beta
      HCG levels, which was repeated 2-3 days later. RESULTS: Initial serum beta-HCG
      levels of the women with ectopic pregnancy and different were significantly lower
      than those in women with threatened abortion (P<0.05), and the increment rate of
      serum beta-HCG in the former was also significantly lower (P<0.05). CONCLUSION:
      Compared with single-time serum beta-HCG detection, dynamic monitoring of serum
      beta-HCG provides more important and reliable evidence for early diagnosis of
      ectopic pregnancy. Transvaginal ultrasonography and in should also be considered
      in the clinical analysis.

PMID- 16793617
TI  - [Relationship between chronic congestive heart failure and sleep-disordered
      breathing in elderly patients].
AB  - OBJECTIVE: To determine the prevalence of sleep disordered breathing (SDB) in
      elderly patients with chronic congestive heart failure (CHF) and explore the
      relations between SDB and left ventricular function. METHODS: By means of
      polysomnography, 56 elderly patients with CHF were divided into non-SDB, mild
      SDB, moderate SDB, and severe SDB groups, and the left ventricular ejection
      fraction (LVEF) was measure by (99)Tc equilibrium radionuclide angiography.
      RESULTS: In the 56 elderly patients with CHF, 38 (67.9%) had SDB, including 12
      (21.4%) mild SDB, 14 (25.0%) moderate SDB, and 12 (21.4%) severe SDB patients.
      Thirty (53.6%) of the 56 patients with CHF had obstructive sleep apnea (OSA), 4
      (7.1%) had central sleep apnea and 22 (39.2%) had mixed sleep apnea. The moderate
      and severe SDB groups had lower minimum arterial oxyhemoglobin saturation during
      sleep than the non-SDB groups, and the apnea-hyponea index was closely related to
      LVEF (r=-0.74, P<0.01). CONCLUSION: The prevalence of SDB, predominantly OSA, is
      high in elderly patients with CHF. Moderate and severe SDB might affect the left
      ventricular function in these patients, who require polysomnography monitoring.

PMID- 16793618
TI  - [Comparative study of warfarin and aspirin for stroke prevention in elderly
      patients with atrial fibrillation].
AB  - OBJECTIVE: To analyze current stroke prevention measures for elderly patients
      with atrial fibrillation. METHODS: A retrospective analysis was conducted of the
      clinical records of elderly patients with atrial fibrillation treated in our
      hospital within the recent 5 years. The distribution of high risk factors for
      different age levels was studied, and the incidence of stroke and complications
      such as hemorrhage were compared between patients treated with warfarin and
      aspirin therapy. RESULTS: Compared with patients of 65 to 75 years old, the
      incidence of complications with other high risk factors was increased in advanced
      age group (over 75 years). Of these patients, 19.0% were treated with warfarin
      and 73.4% with aspirin. Compared with the aspirin group, stroke incidence was
      decreased significantly in warfarin group, which had simultaneously increased
      nonfatal hemorrhage. CONCLUSION: Warfarin can be more effective than aspirin for
      stroke prevention in elderly patients with atrial fibrillation, but in clinical
      practice, the usage rate of warfarin still remains low with insufficient
      monitoring.

PMID- 16793619
TI  - [Association of serum leptin and insulin resistance with nonalcoholic fatty liver
      disease].
AB  - OBJECTIVE: To investigate the relationship among serum leptin, homeostasis model
      assessment of insulin resistance (HOMA-IR), body mass index (BMI) and dyslipidema
      in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Eighty-two
      patients with NAFLD were divided into mild, moderate and severe NAFLD groups
      according histological examination results of the liver. Twenty healthy
      volunteers were chosen as the normal control (NC) group. Fasting insulin,
      glucose, leptin and lipid levels were measured in the 82 patients with NAFLD and
      the BMI calculated. IR index of the patients was calculated according to the HOMA
      method. RESULTS: Leptin, HOMA-IR index, BMI and dyslipidemia showed significant
      differences between NAFLD and NC groups (P<0.05 or 0.01). Leptin and HOMA-IR
      index increased with the exacerbation of NAFLD, both of which were positively
      correlated with the severity of NAFLD. CONCLUSION: Increased leptin level, HOMA
      IR, BMI and dyslipidemia can be important risk factors of NAFLD, and serum leptin
      level and HOMA-IR are positively correlated with the severity of NAFLD.

PMID- 16793620
TI  - [Genetic analysis of translocation of chromosome t(4;9) in a child with rare
      chromosome abnormality].
AB  - A 10-month-old boy suspected of genetic abnormality was admitted for fever and
      coughing. Routine G-banding chromosome analysis of the peripheral blood
      lymphocytes and hereditary pattern analysis on the basis of the karyotypes and
      disease history revealed that the karyotype of the boy's mother was 46,
      XX,t(4;9)(q31;p24), and that of the boy was XY,der(9)t(4;9)(q31;p24)mat. The
      mother was identified as a carrier of balanced translocation of the chromosome
      who gave the abnormal chromosome 9 to her son, and she had only a chance of 1:18
      to have a normal offspring. This case reiterates the importance of antemarital
      examination and prenatal diagnosis for preventing chromosomal diseases.

PMID- 16793621
TI  - [Role of the cut-off value of serum neuron-specific enolase in differentiating
      small cell lung cancer from non-small cell lung cancer].
AB  - OBJECTIVE: To determine the cut-off value of serum neuron-specific enolase (NSE)
      level for distinguishing small cell lung cancer (SCLC) and non-small cell lung
      cancer (NSCLC). METHODS: Serum NSE levels were measured by enzyme-linked
      immunosorbent assay in 137 patients with NSCLC or SCLC, and the best cut-off
      value was analyzed using ROC curve. RESULTS: The positivity rate of serum NSE was
      significantly higher in patients with SCLC than in those with NSCLC (P<0.01). The
      best cut-off value was 15.45 microg/L using ROC curve, which gave a sensitivity
      of 66.7% and specificity of 65.7%. CONCLUSION: Serum NSE level may allow simple
      and cost-effective differentiation of SCLC and NSCLC.

PMID- 16793622
TI  - [Expression of angiogenesis-related factors in invasive breast cancer and its
      clinical significance].
AB  - OBJECTIVE: To investigate the relation between expression of angiogenesis-related
      factors, namely vascular endothelial growth factor (VEGF) and transforming growth
      factor-beta1 (TGFbeta(1)), and microvessel count (MVC) in invasive breast cancer
      and analyze its clinical implications. METHODS: VEGF, TGFbeta (1) and CD34
      expressions in 62 surgical specimens of invasive breast cancer and 12 normal
      breast specimens were examined by immunohistochemistry and HE staining. MVC was
      calculated according to the quantification of positive CD34 expression.
      Clinicopathological characteristics of the patients including age, tumor size,
      histological type and auxiliary lymph node metastasis were recorded and compared
      with the results of MVC VEGF and TGFbeta1 expression and detection. RESULTS: MVC
      and of VEGF and expressions TGFbeta (1) in invasive breast cancer group (55.62
      /+11.07, 51.61%, 56.45%, respectively) were greater than those in the normal
      control group (12.65-/+5.73, 16.67%, 16.67%, respectively, P<0.05). MVC and the
      positivity rates of VEGF and TGFbeta (1) expressions were 65.53-/+20.36, 68.75%
      and 78.13%, respectively, in invasive breast cancer patients with axillary lymph
      node metastasis, significantly higher than those without metastasis (P<0.05). MVC
      was correlated with VEGF and TGFbeta (1) expressions in that MVC was
      significantly higher in patients positive for VEGF and TGFbeta (1) (62.82-/+16.31
      and 59.35-/+12.76) than in those negative for their expressions (51.16-/+12.53
      and 50.80-/+15.62, P<0.05). Significant correlation was also found between VEGF
      and TGFbeta (1) expressions (P<0.05). CONCLUSION: The interaction between VEGF
      and TGFbeta (1) mediates angiogenesis, and MVC and VEGF and TGFbeta (1)
      expressions are correlated to lymph node metastasis, which may provide reference
      for prognostic evaluation of invasive breast cancer.

PMID- 16793623
TI  - [Clinical value of adjuvant therapy with estrogen for postpartum hemorrhage].
AB  - OBJECTIVE: To investigate the clinical efficacy of estrogen in management of
      postpartum hemorrhage due to uterine atony. METHODS: Totalling 112 puerperants
      with postpartum hemorrhage due to uterine atony were randomly assigned into 2
      groups and received routine managements for uterine atony such as uterine massage
      and uterotonics administration. The puerperants in one group (n=52) was treated
      with 4 mg estradiol benzoate injected intramuscularly, and the amount of blood
      loss 2 h after delivery and between 2 and 24 h after delivery was recorded.
      RESULTS: There were significant differences in vaginal blood loss at 2 h after
      delivery between the 2 groups (P<0.05). The puerperants with estrodiol benzoate
      treatment had blood loss of 589.6-/+226.4 ml at 2 h and 110.8-/+76.2 ml within 2
      24 h after delivery, which were both less than those in the control group (864.5
      /+359.5 ml and 161.5-/+98.3 ml, respectively). Postpartum hysterectomy was
      performed in 3 cases of the control group while none in estradiol benzoate
      treated group. In the mothers and neonates, no major adverse effects were
      observed. CONCLUSION: Estrogen shows cooperative efficacy with uterotonics in
      stimulating uterine contraction for managements of postpartum hemorrhage due to
      uterine atony, and can be of value in clinical application.

PMID- 16793624
TI  - [Long-term follow-up results of synovectomy for rheumatoid knee].
AB  - OBJECTIVE: To continuously observe the long-term effects of synovectomy for
      improving joint damage and quality-of-life in patients with the rheumatoid knee.
      METHODS: Twenty-one consecutive patients with rheumatoid arthritis (RA) involving
      24 knees underwent open synovectomy from November 1988 to January 1997 between
      November 1988 and January 1997. The changes in radiographic damage were assessed
      with Larsen score on plain films before and 6 months after surgery with
      subsequent annual assessment for 8 years, and the functional recovery of the
      patients was also evaluated with Health Assessment Questionnaire (HAQ) at the
      same time. RESULTS: The radiographic joint damage and juxta-articular
      osteoporosis or bone erosion was ameliorated after surgery in all the patients.
      Larsen score began to decrease 6 months after the operation, and the best effects
      were achieved at one year and maintained for at least 5 years after the
      operation, but then followed by recurrence of joint lesions. HAQ scores were
      improved after the surgery with the best effects observed 6 months after the
      operation lasting for over 2 years. HAQ score gradually decreased 4 years after
      the operation till reaching the preoperative scores. CONCLUSION: Synovectomy in
      the patients with rheumatoid knee not only reverses progressive joint damage, but
      also improves juxta-articular bone erosions and the patients' quality of life.
      However, radiographic joint damage and functional deterioration may recur due to
      hyperplasia of the inflammatory synovium in the long term after operation,
      suggesting that the inflammatory synovium participates in local joint damage with
      bone erosions and systemic pathologic process of RA.

PMID- 16793625
TI  - [Intensity-modulated radiation combined with Delisheng injection for
      naspharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of intensity-modulated radiation
      therapy(IMRT) combined with Delisheng injection for treatment of nasopharyngeal
      carcinoma (NPC). METHODS: Sixty-six patients with pathologically confirmed NPC
      (stage II and III) were randomized into therapeutic group and control group.
      Patients in the therapeutic group were treated with Delisheng injection in
      addition to IMRT and those in the control group with IMRT alone. RESULTS: No
      significant difference in the response rate occurred between the two groups. The
      incidence of adverse effects was significantly lower in the therapeutic group
      than in the control group, and the humoral immunity was improved in the former.
      CONCLUSION: Delisheng injection can decrease the side effects of IMRT and improve
      humoral immunity in NPC patients.

PMID- 16793628
TI  - Vasopressin and platelets: a concise review.
AB  - Arginine vasopressin (AVP or vasopressin) is a neurophypophyseal peptide hormone
      with both vasopressor and antidiuretic properties. This review will briefly
      discuss the chemistry and physiology of AVP, with the main focus being on AVP and
      the hemostatic system. Recent data on the effects of AVP, and its analogues, on
      platelet function will be highlighted. AVP-induced platelet activation could
      explain, in part, the benefit seen with AVP infusions in gastrointestinal
      bleeding. These data also suggest that AVP may have a role in physiologic
      hemostasis and platelet activation.

PMID- 16793627
TI  - The platelet Ca2+ transport ATPase system.
AB  - The Ca2+ signal accompanying cell function involves the activities of plasma
      membrane Ca2+ transport ATPases (PMCA) which transport Ca2+ ions out of the cell
      and those of sarco/endoplasmic reticulum Ca2+ transport ATPases (SERCA), which
      pump Ca2+ ions into intracellular Ca2+ pools. Although a platelet Ca2+ transport
      ATPase was described three decades ago, for a long time it remained poorly
      understood in terms of its cellular localization and identity. By integrating
      data obtained during recent years, including newly available information in the
      literature for the PMCAs and aspects of our work concerning the SERCAs, the
      present review will show how the overall view of the platelet Ca2+ATPase system
      has to be modified due to the presence of a number of Ca2+ATPases in these cells.
      These Ca2+ATPases include a typical 144 kDa PMCA protein, although its molecular
      identity still remains to be established, expressed together with a multi-SERCA
      system constituted by the ubiquitous 100 kDa SERCA 2b isoform, the 97 kDa SERCA 3
      isoform and a new 97 kDa SERCA isoform recognized by the monoclonal antibody
      termed PL/IM 430 which also remains to be identified. The new paradigm of the
      platelet multi-Ca2+ATPase system will be discussed including: (i) the problems
      solved, as it has now become possible to reconciliate previous contradictory
      observations and (ii) those which still remain due to the fact that the platelet
      Ca2+ATPase system is more complex than previously assumed. Finally, to put this
      complexity of the platelet Ca2+ transport ATPase system into perspective, the
      biological significance of the multi-SERCA system in the context of Ca2+
      signalling will be tentatively discussed in an attempt to produce a model of the
      organization of the intracellular Ca2+ pools in platelets.

PMID- 16793626
TI  - [Relation of serological markers of hepatitis B virus and alanine transaminase to
      hepatic tissue pathology in patients with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the association of serological markers of hepatitis B
      virus (HBV) and alanine transaminase (ALT) with hepatic tissue pathology in
      patients with chronic hepatitis B. METHODS: The serological marker of HBV, liver
      function and liver biopsy of 133 patients with chronic hepatitis B were measured
      and evaluated. The patients were divided into 4 groups according to HBeAg and HBV
      DNA positivity. Hepatic necrosis/inflammation grade and hepatic fibrosis were
      compared between the groups. RESULTS: Hepatic histological examination of all
      these patients showed inflammation, necrosis and different degrees of fibrosis.
      In patients with normal serum ALT, liver biopsy showed different degrees of
      inflammation, hepatic fibrosis, and even hepatocirrhosis. In patients with
      abnormal serum ALT negative for HBeAg, hepatic tissue inflammation and fibrosis
      were more serious. Hepatic tissue pathology was not paralleled with the level of
      HBV replication. CONCLUSION: Evaluation of the liver disease can not depend
      solely on serum ALT and viral loading in these patients. Hepatic tissue pathology
      in patients with chronic hepatitis B should be served as the most reliable
      evidence for evaluating hepatitis conditions and making the decision on antiviral
      therapy.

PMID- 16793629
TI  - A human megakaryoblastic cell cycle regulation cell line, CMK and its cell cycle
      regulation.

PMID- 16793630
TI  - Influence of the alpha-adrenoreceptor naftopidil and doxazosin, on adrenaline
      induced serotonin platelets: comparison with the antagonists, collagen and efflux
      by human effects of nifedipine.
AB  - Collagen (5 microg/ml) stimulation of washed platelets increased endogenous
      serotonin (5-HT) release to the medium from 13.88 1.39 to 188.67 26.37 pmol/108
      platelets ( P < 0.001). Adrenaline (16 microM) also increased 5-HT release, from
      11.0 1.46 to 110.6 29.9 pmol/108 platelets ( P < 0.02). Naftopidil enhanced
      collagen-induced 5-HT efflux; significant increases occurred with 2 microM
      (+71.6%, P < 0.01), 10 microM (+89.1%, P < 0.01) and 40 microM (+69.7%, P <
      0.01). With 0.4 muM and 2 microM naftopidil, adrenaline-induced 5-HT release was
      enhanced, albeit non-significantly, whilst with 10 microM and 40 muM naftopidil
      release was reduced (40 microM,-58.5%, P < 0.05). Doxazosin increased collagen
      induced 5-HT release, significant increases being recorded with 7.5 microM
      (+81.7%, P < 0.05) and 30 microM (+78.4%, P < 0.05). Adrenaline-induced 5-HT
      release was also increased by doxazosin, but not significantly. Collagen
      stimulated 5-HT release was inhibited by nifedipine (7 microM,-38.8%, P < 0.05;
      28 microM, -61.2%, P < 0.001). These data suggest that the-antagonists,
      naftopidil and doxazosin, and the Ca2+ channel blocker, nifedipine, influence
      agonist-induced platelet 5-HT release through different mechanisms. Thus
      naftopidil and doxazosin may possess 5-HT transporter-blocking activity. The
      observation that naftopidil inhibited, adrenaline-induced 5-HT release may
      indicate that naftopidil also inhibits adrenaline uptake and exchange with dense
      granular 5-HT, with consequent inhibition of 5-HT release and platelet
      aggregation. The data obtained with nifedipine are consistent with 5-HT release
      being reduced as a result of its inhibitory action on platelet Ca2+ mobilisation.

PMID- 16793631
TI  - The role of platelets in the coagulopathy of heatstroke- a study of platelet
      aggregation in heatstroke patients during the Makkah pilgrimage (Haj) to Makkah.
AB  - Platelet aggregation was undertaken in platelet rich plasma in 34 heat-stroke
      patients during the Muslim pilgrimage (Haj) to Makkah; 18 were males and 16 were
      females; their ages ranged from 36 to 80 years (mean SD = 58 10). Platelet
      aggregability, on arrival at the Heatstroke Centres, was markedly inhibited in
      response to adrenaline, collagen, arachidonic acid and ristocetin but not to ADP.
      Responses to decreasing ADP doses (20.0, 2.0, 1.0 and 0.5 micromol/l) showed
      hyperaggregability in 12 patients, inhibited responses in 16 and normal responses
      in 6 patients. Aggregation responses were not significantly different when
      comparing patients with bleeding manifestations ( n = 10), with those without
      bleeding ( n = 24). Haemostatic parameters including plasma fibrinogen, ATIII and
      platelet count, were markedly reduced in the two patient groups who showed
      hyperaggrebable and depressed aggregation responses, but not in those with normal
      responses. These results lead us to conclude that: (1) platelet activation is a
      frequent feature of heatstroke; (2) in heatstroke altered aggregation responses,
      whether hyperaggregable or depressed, occur simultaneously with a consumption
      coagulopathy.

PMID- 16793632
TI  - Inhibitory effect of lysophosphatidylcholine and phospholipase A2-treated low
      density lipoproteins on receptor-dependent regulation of {Ca2+}i in platelets.
AB  - Treatment of LDL with phospholipase A from bee venom resulted in formation of
      lipid-protein particles (pl2 LDL) with increased content of
      lysophosphatidylcholine (LPC). At the same time, composition of other lipids and
      protein structure were unaffected. Both pl-LDL and LPC abolished PAF-, ADP- and
      thrombin-induced Ca2+ elevation in platelets and platelet aggregation, while LDL
      had no effect on hormone-stimulated increase in the intracellular Ca2+ content
      ({Ca2+}i). The effect persisted in Ca2+-free medium, indicating that pl-LDL and
      LPC also abolish Ca2+ mobilisation from intracellular stores. Neither LPC nor pl
      LDL changed platelet Ca2+ levels and inhibited platelet aggregation induced by
      thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca2+ ATPase. The
      inhibitory effect depended on LPC concentration, incubation time and the
      structure of LPC: lysophosphatidylethanolamine and phosphatidylcholine produced
      no inhibitory effect. The half-maximum-effective concentrations were the same for
      LPC and pl-LDL (2-4 microM). The results obtained indicate that LPC and pl-LDL
      inhibit the receptor-dependent increase in Ca2+. It can be suggested that the
      effect of LPC is mediated by redistribution of the plasma membrane integral
      proteins, which leads to disintegration of the intracellular signalling systems.

PMID- 16793633
TI  - Influence of cytochalasin B (CB) on GP Ib distribution after thrombin or TRAP and
      before surface activation.
AB  - The receptor for von Willebrand factor (vWF) on human platelets, glycoprotein
      (GP) Ib/IX, has been shown in our studies to be an immobile complex when
      stimulated in suspension or on surfaces. Recent investigations have revealed that
      GP Ib/IX remains immobile on platelets activated in suspension followed by
      exposure to formvar surfaces that cause the cells to spread. However, since
      channels of the open canalicular system (OCS) are evaginated back on to the
      exposed surface during spreading, it was suggested that our study missed the
      clearance of GP Ib/IX from the exposed surface to internal membranes. The present
      study has added cytochalasin B after exposure of platelets to thrombin or TRAP in
      suspension in order to prevent spreading and movement of GP Ib/IX during
      subsequent exposure to surface activation on formvar grids. Results indicate that
      GP Ib/IX receptors remain randomly dispersed from edge to edge on platelets
      activated by thrombin or TRAP in suspension 10 minutes before treatment with CB
      followed by surface activation. Statistical analysis of the frequency of
      immunogold particles binding to monoclonal antibodies attached to GP Ib/IX
      revealed no significant reduction in frequency, translocation from cell edges or
      concentration of GP Ib/IX receptors in or around channels of the OCS. Results
      support the concept that GP Ib/IX is not cleared from exposed surfaces to the OCS
      of platelets activated by thrombin or TRAP and surface activation.

PMID- 16793635
TI  - Heparin-induced thrombocytopenia: an under-diagnosed syndrome? Proceedings of a
      workshop held in London on 1 November 1996.

PMID- 16793634
TI  - The effects of taxol, a potent platelet antiaggregant, may be due to its
      microtubular stabilization activity.

PMID- 16793636
TI  - Heparin-induced thrombocytopenia: an under-diagnosed syndrome? Proceedings of a
      workshop held in London on 1 November 1996. Consensus overview.

PMID- 16793637
TI  - Cytokines, platelet production and hemostasis.
AB  - A number of hematopoietic growth factors and other cytokines are capable of
      altering platelet production and function. Enhancement of these processes may be
      exploited to ameliorate bleeding propensity in thrombocytopenic patients. Under
      certain circumstances, cytokines may have adverse effects on the hemostatic
      system, potentially involved in thrombogenesis and atherogenesis. Inhibition of
      those cytokines may prove to be a useful experimental approach to investigate
      their potential pathophysiologic role.

PMID- 16793638
TI  - Flow cytometric assessment of glycoprotein movements in platelets.

PMID- 16793639
TI  - Scott syndrome: an inherited defect of the procoagulant activity of platelets.
AB  - Anionic phospholipids, chiefly phosphatidylserine, are essential for the assembly
      of the characteristic enzyme complexes of the blood coagulation cascade at the
      surface of stimulated platelets and derived microparticles. In the resting cell,
      these phospholipids are sequestered in the inner leaflet of the plasma membrane.
      Scott syndrome is an extremely rare bleeding disorder that confirms the essential
      role of these anionic procoagulant phospholipids. In Scott patients,
      phosphatidylserine externalization and microparticle shedding are dramatically
      impaired. This functional deficiency is clearly evidenced by the measurement of
      residual prothrombin in serum. The recent detection of a familial Scott syndrome
      testifies to the genetic origin of the defect. Symptomatic Scott patients present
      provoked hemorrhages and are probably homozygous for the disorder whereas
      asymptomatic children are probably heterozygous. The Scott phenotype can be
      detected in platelets, red cells and lymphocytes by functional prothrombinase
      assay and flow cytometry. Intermediate degrees of phosphatidylserine exposure and
      vesiculation are observed in cells from the asymptomatic heterozygous offspring
      when compared to those from their homozygous defective parent and healthy
      subjects. The functional and molecular characterization of mutated element(s) in
      Scott syndrome should be of valuable help for the understanding of phospholipid
      transmembrane migration, also termed flip-flop, its possible links with membrane
      vesiculation, and the eventual implications in thrombotic or apoptotic processes.

PMID- 16793640
TI  - Abnormalities in platelet membrane structure and function in Alzheimer's disease
      and ischaemic stroke.

PMID- 16793641
TI  - Signal transduction in the platelet activation induced by IgG anti-streptokinase
      and anisoylated plasminogen-streptokinase activator complex.
AB  - Streptokinase (SK) is one of the plasminogen activators currently used in
      therapeutics. SK antibodies may appear in the blood after thrombolytic therapy
      with SK or after-hemolytic streptococci infection. Such antibodies may both
      activate platelets and neutralize the ability of SK to convert plasminogen into
      plasmin. We previously demonstrated that platelet activation induced by the
      combination of IgG anti-SK and anisoylated plasminogen-SK activator complex
      (APSAC) is mediated by Fc gamma RIIa1 receptor. However, the mechanism by which
      IgG anti-SK and APSAC (or SK) transduce an activating signal across the platelet
      plasma membrane remains unknown. We have demonstrated in the present study that
      the platelet aggregation induced by the combination of IgG anti-SK and APSAC is
      accompanied by an increase in inositol phosphate, Ca2+ mobilization and
      thromboxane (Tx) A2 generation. Neomycin, erbstatin and GF 109203X, which inhibit
      phospholipase C (PLC), protein tyrosine kinase (PTK) and protein kinase C (PKC)
      activities, respectively, abolished platelet aggregation induced by IgG anti-SK
      plus APSAC, indicating the pivotal roles of the PLC, PTK and PKC pathways in this
      immunological activation. In addition, TxA2 generation is also important since
      aspirin, a cyclooxygenase inhibitor and SQ 29548, a TxA2 receptor antagonist,
      showed significant inhibition of the platelet response. The contribution of
      released ADP was confirmed using apyrase, which significantly inhibited IgG anti
      SK plus APSAC-induced platelet aggregation. Finally, WEB 2086, a platelet
      activating factor (PAF) receptor antagonist, was not effective, indicating that
      PAF is not involved in this process. APSAC- or SKinduced platelet activation may
      limit the therapeutic effectiveness of the drug and may contribute to the
      pathogenesis of early reocclusion. The study of the mechanism leading to APSAC
      induced platelet activation could be relevant for a better understanding of the
      physiopathology of immune complex disorder diseases and thrombolytic treatment
      failure.

PMID- 16793642
TI  - Differential formation of a bioactive antiaggregating substance (BAS) by layers
      of the vein wall.
AB  - Human umbilical veins were analyzed with and without endothelium in order to
      study the ability of endothelial cells and subendothelium to release a bioactive
      anti-aggregating substance (BAS: MW > 30 kDa) independent of prostacyclin (PGI ).
      To evaluate the role of the subendothelium, the endothelial cells were removed by
      rubbing on filter paper for 1 min. We performed a histopathological study of the
      vessels using hematoxylin and eosine, and stained for elastic tissue fibers in
      order to confirm the presence of endothelium. The supernatant from incubated
      vascular rings was partially purified by Sephadex G-50 to rule out PGI . The void
      volume fractions were collected and the anti-aggregating activity was tested on
      platelet aggregation induced by arachidonic acid, ADP, collagen and epinephrine.
      We observed that the activity was taking place with the use of the intact
      endothelium while there was no activity in the denuded vein. These observations
      could help to explain the well known antithrombotic properties of vascular
      endothelium.

PMID- 16793643
TI  - Regulation of PAF-induced platelet responses by cyclic nucleotides.
AB  - The existence of cross-talk mechanisms between the cyclic nucleotide system and
      other transduction systems involved in PAF-activated platelets is described in
      this study. A protein of 125 kDa, identified as pp125FAK, is tyrosine
      phosphorylated by PAF in a time- and concentration-dependent manner. The presence
      of a cAMP- or a cGMP-elevating agent, used alone or in combination, together with
      PAF diminished tyrosine phosphorylation. The sensitivity to cAMP shown by PAF
      induced pp125 phosphorylation on tyrosine residues was similar to PAF-induced
      phosphorylation of a 47-kDa protein (pp47) on serine and threonine. In contrast,
      the latter was not affected in the presence of a cGMP-elevating agent, although
      it was able to enhance synergistically the inhibitory effect of forskolin. Data
      reported herein also show that pp47 phosphorylation and serotonin secretion are
      not closely correlated. Accordingly, sodium nitroprusside (SNP) did not have any
      effect on phosphorylation of pp47, but it was able to inhibit serotonin secretion
      when added alone, and it showed a synergistic inhibitory action with forskolin.

PMID- 16793644
TI  - Persistence of low platelet adhesiveness in von Willebrand disease during
      pregnancy.
AB  - Platelet adhesiveness (PA) is a valuable measure of ex vivo platelet function. A
      low PA is a usual feature of von Willebrand disease (vWd). However, PA has rarely
      been measured during vWd pregnancies. The aim of this work was to observe the
      behaviour of PA in vWd pregnancies. PA was measured during pregnancy in 33 vWd
      patients. Intrapregnancy PA remained low without any significant variation
      compared with non-pregnancy values. Advanced gestation was not accompanied by any
      increase in PA in spite of the concomitant normalization showed by the other
      markers of vWd. A low intrapregnancy value was not predictive of an increased
      risk of bleeding at labour. A low PA could be the only clue for vWd during
      gestation warranting both a vigilant postpartum attitude and a thorough
      haemostatic evaluation after pregnancy.

PMID- 16793645
TI  - Soluble P-selectin assay: importance of correct anticoagulant choice.
AB  - P-selectin is stored preformed in the-granules of platelets. Previous studies
      show-thromboglobulin, also stored in-granules can be readily released from
      platelets during the processing of whole blood. This artefactual release was
      rectified by using combination of various anti-platelet and anticoagulant
      compounds placed in the collecting tube. We investigated the levels of sP
      selectin from 40 volunteers, comparing two anticoagulants, tri-sodium citrate,
      CTAD (a mixture of sodium citrate and citric acid, theophylline, adenosine and
      dipyridamole) plus iloprost and serum. Iloprost, a stable prostacyclin analogue,
      is a potent anti-platelet agent. We found significantly lower levels of sP
      selectin ( P < 0.0001, paired t-test ) measured from blood collected into CTAD
      and iloprost compared to levels measured from either citrated plasma or serum. We
      suggest that plasma levels obtained from the blood collected into a CTAD tube
      containing iloprost are likely to more accurately reflect the true levels of
      circulating sP-selectin than those obtained when test-tube activation of
      platelets is allowed to continue in vitro . </abs>

PMID- 16793646
TI  - Differential effects of native and oxidatively modified low-density lipoproteins
      on platelet function.
AB  - Low-density lipoproteins (LDL) have been various reported to induce platelet
      aggregation independently and/or sensitise platelets to other agonists. In these
      earlier studies the extent of oxidation of LDL was not always reported or
      addressed. We have now investigated the effects of native, minimally modified and
      fully oxidised LDL (0-1g apolipoproteinB /l on platelet function using platelet
      aggregometry and fluorescence activated 100 flow cytometry. Native LDL did not
      activate isolated platelets but inhibited ADP- and thrombin-induced aggregation
      of isolated platelets by 51% in the presence or absence of added fibrinogen.
      Longer pre-incubations were required to produce a comparable inhibition by native
      LDL on platelets in plasma. Flow cytometric analysis showed that native LDL
      inhibited ADP-induced fibrinogen binding by up to 38%. In contrast, minimally
      modified LDL induced primary platelet aggregation and fibrinogen binding in the
      absence of other agonists, enhanced both submaximal (1 2 lmol/l) ADP-induced
      aggregation, fibrinogen binding and degranulation (CD63 and P-selectin
      expression). Fully oxidised LDL, however, inhibited ADP-induced platelet
      aggregation and fibrinogen binding. The effects of minimally modified LDL on
      platelet aggregation could be reproduced partially by adding 15-hydroperoxy
      eicosatetraenoic acid to native LDL. These data indicate that the extent of
      oxidation of LDL is critical in determining their effects on platelet function.
      Native LDL did not activate platelets, whilst minimally modified LDL exerted a
      pro-aggregatory effect, possibly due to the presence of lipid hydroperoxides near
      to the concentration range found in pathological states.

PMID- 16793647
TI  - The H1-histamine antagonist dithiaden inhibits human platelet function in vitro.
AB  - The H-histamine receptor antagonist Dithaden inhibited in a dose-dependent
      manner, human platelet 1 aggregation in vitro that was induced with stimuli in
      the following rank order of potency: thrombin > A23187 > adrenaline > ADP. The
      aggregation of platelets in plasma induced with adrenaline was inhibited by
      Dithiaden (DIT) (both the first and the second phase) and the onset of the second
      phase was prolonged significantly. In a concentration-dependent manner DIT
      inhibited thrombin- and calcium ionophore A23187-induced {3H}arachidonic acid
      liberation from, and peroxidation (measured as malondialdehyde formation) of
      membrane phospholipids. The same effect of DIT was found for the inhibition of
      thromboxane B suggested that DIT does not inhibit stimulated platelets at
      specific histamine receptors sites but rather at the phospholipase A and
      thromboxane synthase level. Results from in vitro experiments should be verified
      in 2 vivo . generation. It is 2.

PMID- 16793648
TI  - Lysophosphatidic acid induces protein tyrosine phosphorylation in the absence of
      phospholipase C activation in human platelets.
AB  - Lysophosphatidic acid is a biologically active phospholipid able to induce cell
      proliferation and platelet aggregation. In this study we investigated the
      biochemical mechanisms of platelet activation by lysophosphatidic acid. We found
      that lysophosphatidic acid stimulated 4-azidoanilido-{ alpha 32P}GTP to a 40-kDa
      protein on platelet membranes. Moreover, lysophosphatidic acid induced the rapid
      decrease of the intracellular concentration of cAMP in intact platelets,
      indicating that this lipid activates platelets by binding to a membrane receptor
      coupled to the inhibitory GTP-binding protein Gi. In agreement with a receptor
      mediated action, we found that platelet activation by lysophosphatidic acid
      underwent homologous desensitization. In the absence of extracellular CaCl ,
      lysophosphatidic acid did not induce platelet aggregation, and did not stimulate
      phospholipase C. However, under the same conditions, lysophosphatidic acid
      produced the rapid tyrosine phosphorylation of several platelet proteins. This
      effect was not mediated by the formation of thromboxane A . Our results
      demonstrate that, in lysophosphatidic acidstimulated platelets, activation of
      protein-tyrosine kinases occurs in the absence of phospholipase C activation and
      platelet aggregation, and may be directly related to the activation of the G
      protein-coupled lysophosphatidic acid-receptor. the binding of the photoreactive
      GTP-analog 2 2.

PMID- 16793650
TI  - Erratum.

PMID- 16793649
TI  - Letter to the editor.

PMID- 16793651
TI  - Inherited disorders of platelet alpha-granules.
AB  - Platelet alpha-granules are the storage site for the internal membrane
      glycoprotein P-selectin and for a variety of megakaryocyte-synthesized and plasma
      derived soluble proteins. Quantitative and/or qualitative abnormalities in alpha
      granules are found in a number of inherited bleeding disorders, including gray
      platelet syndrome, alphadelta-storage pool deficiency, the Quebec platelet
      disorder, and in some patients with dysmegakaryopoietic thrombocytopenia. In
      addition, single alpha-granular protein deficiencies are seen in other bleeding
      disorders,including factor V deficiency, afibrinogenemia, Glanzmann's
      thrombasthenia, von Willebrand disease, and plasminogen-activator inhibitor-1
      deficiency. The excessive bleeding that occurs in patients with inherited
      abnormalities of platelet alpha-granules indicates that the proteins stored
      within this compartment are important for normal hemostasis. The clinical and
      laboratory features of these different, inherited platelet storage pool disorders
      suggest unique molecular and biochemical defects are responsible for these
      conditions. However, the genetic causes of these disorders are largely unknown.
      This paper reviews our current knowledge of the inherited disorders of platelet
      alpha-granules.

PMID- 16793652
TI  - Functional and clinical significance of thrombospondin.

PMID- 16793653
TI  - Phosphorylation reactions and the affinity state of platelet integrin
      alphaIIbbeta3.

PMID- 16793654
TI  - Genetic control of platelet activation in inbred mouse strains.
AB  - Platelet activation in inbred mouse strains was studied using expression of P
      selectin as a marker of activated platelets. P-selectin expression in response to
      no added stimulus (spontaneous activation) or in response to adenosine
      diphosphate (ADP) and epinephrine or thrombin, was assessed using a flow
      cytometric assay. Wide variation in the responsiveness of different strains was
      observed with strains SJL and AKR in particular showing very high levels of
      spontaneous activation. Genetic studies suggest that this phenomenon is under
      control of a small number of genes and that the same loci are probably
      responsible for the high activation of both SJL and AKR. Bone marrow transplant
      experiments show that the trait is expressed in the platelet itself. Screening of
      SWXJ and AKXD recombinant inbred lines suggests that one of the responsible genes
      is located on chromosome 3.

PMID- 16793655
TI  - Functional characterization of GPIIb- and GPIIIa-specific monoclonal antibodies.
      Further evidence for the existence of agonist-specific activated states of the
      platelet fibrinogen receptor.
AB  - In this work human platelet aggregation induced in vitro by ADP, collagen,
      arachidonic acid and U-46619 (a thromboxane A(2) analogue) was used as a
      functional test to characterize 19 anti-GPIIb (M series) and anti2 GPIIIa (P
      series) monoclonal antibodies whose epitope location is known for most of them.
      Additionally, flow cytofluorimetry was applied to study the epitope expression of
      these antibodies in resting, EDTA-treated and SFLLRN peptide (thrombin receptor
      agonist)-activated platelets. Antibodies M6 (epitope located at GPIIbH 657-665),
      P23-7 (GPIIIa 114-122) and P40 (GPIIIa 262-303) bind weakly to only 43%, 70% and
      66%, respectively, of the resting platelet population. This binding was enhanced
      in EDTA-treated and in activated platelets. Platelet activation enhances the
      apparent binding of most of the other antibodies. Further evidence on the
      existence of agonist-specific activated states of GPIIb/IIIa was provided by the
      agonist-dependent immunochemical inhibition in vitro of platelet aggregation by
      some of the anti-subunit antibodies studied here. The most notable cases are
      those of P40 and M6, which at 140 nM inhibit most, the platelet aggregation
      induced by arachidonic acid and U-46619. On the other hand, three of the most
      strong and agonist-independent inhibitors, P37 (GPIIIa 101-109), P97 and P95-2
      (GPIIIa N-terminal half) bind to resting platelets with high affinity (5-8 nM),
      compete with each other for binding to GPIIb-IIIa and their epitopes are located
      at the N-terminal domain of GPIIIa, where the receptor ligand binding site(s)
      have been found. Given that the formation of activated GPIIb-IIIa (GPIIb-IIIa*)
      is the first step at which the anti-subunit antibodies can intervene as
      inhibitors and that agonist-specific inhibitors should block only agonist
      specific steps, while nonspecific inhibitors should block steps common to all the
      agonists, then our present work support the hypothesis that there are different
      agonist-specific GPIIb-IIIa*s or, alternatively, different receptor environments,
      that can be specifically blocked by some of the antibodies. These results add to
      earlier evidence on agonist-dependent ligand specificity and activated states
      found for this and other integrins. Finally, the correlation between the in vitro
      inhibition of platelet aggregation and the antithrombotic activity in vivo is
      discussed for these antibodies.

PMID- 16793656
TI  - Proinflammatory cytokines and hemostatic system in patients with chronic
      obstructive pulmonary disease.
AB  - The prothrombotic state frequently observed in patients with chronic obstructive
      pulmonary disease (COPD) may be related to a systemic inflammatory response. In
      the present study plasma interleukin-6 (IL-6), IL-2 and IL-1beta levels have been
      investigated in 33 patients with COPD. In vitro platelet activity, plasma C
      reactive protein (CRP) and fibrinogen levels were also determined in all
      patients. The results obtained demonstrated that plasma IL-6 levels were
      significantly higher in the patient group compared with a control population age
      and sex-matched ( P < 0.02), while plasma IL-2 and IL-1beta levels were not
      significantly modified. An overall condition of platelet hyperactivity in COPD
      patients was also observed. A comparative analysis of platelet activity and blood
      gas levels demonstrated a correlation between platelet hyperactivity and a severe
      impairment of oxygen ( P < 0.001) and carbon dioxide tensions ( P < 0.01).
      Finally, a statistical analysis of the population under study showed the presence
      of a significant correlation between elevated plasma IL-6 ( P < 0.001) and IL
      1beta levels ( P < 0.007), and an increased sensitivity of platelets to
      arachidonic acid, suggesting a possible correlation between the inflammatory
      response and the prothrombotic state observed in patients with COPD.

PMID- 16793657
TI  - Cholesterol enhances the adhesion of human platelets to fibrinogen: studies using
      a novel fluorescence based assay.
AB  - This communication reports investigations on the effect of platelet cholesterol
      content on adhesion of platelets to a fibrinogen coated surface. The adhesion of
      platelets stimulated with thrombin or ADP was dramatically increased when the
      platelet cholesterol content was enriched by incubation with cholesterol
      containing phosphatidylcholine vesicles. In contrast, ADP failed to promote the
      adhesion of platelets to fibrinogen after they had been depleted of cholesterol,
      either by incubation with phosphatidylcholine vesicles or by brief exposure to
      cholesterol oxidase. By comparison, the adhesion of resting platelets to
      fibrinogen coated surface was unaltered following either enrichment or depletion
      of cholesterol. These data were obtained using a novel method of measuring the
      adhesion of platelets to a protein coated surface based upon the fluorescent
      detection of platelets containing the fluorescent probe octadecyl rhodamine
      (R(18)). R(18) was incorporated into platelet membranes using standard ethanol
      injection techniques at room temperature for 30 min. The platelets were
      introduced into fibrinogen coated wells of a 96-well microtiter plate in the
      presence of various cations and stimulatory or inhibitory ligands. The plate was
      then incubated at room temperature without agitation for various periods of time.
      Adhesion measured in this manner had characteristics similar to those reported
      using other methods. Thus the extent of adhesion ranged from 1-4% under basal
      conditions, and was increased in a dose-dependent manner by Mg(2+) and Ca(2+),
      increased further by ADP, collagen or thrombin and not affected by prostacyclin.

PMID- 16793658
TI  - An investigation into the release and mobilisation of sulphate-conjugated
      catecholamines by human platelets.
AB  - Collagen (5-160 microg/ml) induced release of free and sulphate conjugated
      noradrenaline (NA), adrenaline (Ad) and dopamine (DA) by platelets in platelet
      rich plasma (PRP) was investigated in human subjects. Stimulated efflux of free
      NA, Ad and DA to the plasma (platelet-poor plasma; PPP) increased in a
      concentration-dependent manner, NA release being reflected by reduced platelet
      free NA contents. Collagen EC(50) values for free NA, Ad and DA release were
      similar, i.e. 3.8, 3.3 and 4.5 microg/ml collagen, respectively. Subtracting
      resting PPP free catecholamine (CA) concentrations from those obtained with 160
      microg/ml collagen revealed that 52%, 31% and 33% of PPP free NA, Ad and DA,
      respectively, resulted from collagen stimulation. Under resting conditions
      sulphate conjugated NA, Ad and DA accounted for 74%, 78% and 99% of total (sum of
      free and sulphate conjugated) PPP concentrations. Collagen elicited concentration
      dependent release of sulphate conjugated DA and, to a lesser extent, NA, but not
      Ad. Sulphate conjugated NA release was mirrored by decreases in platelet sulphate
      conjugated NA contents. Resting platelet sulphate conjugated NA and Ad
      represented 42% and 50% of total (free plus sulphate conjugated) NA and Ad
      concentrations. EC(50) values for sulphate conjugated DA and NA release were,
      respectively, 14.5 and 6.25 microg/ml collagen, which exceeded the values for
      free DA and NA release by 222% and 64%. With 160 microg/ml collagen 44% and 15%
      of PPP sulphate conjugated DA and NA, respectively, had resulted from platelet
      activation, and of the total (sum of free and sulphate conjugated) DA and NA
      released, 99.5% and 39.7% were sulphate conjugated. Total (sum of PPP and
      platelet) free and sulphate conjugated NA and Ad concentrations were unaltered by
      collagen stimulation indicating that platelet activation does not cause
      mobilisation (i.e. hydrolysis) of platelet sulphate conjugated CA. Thus, platelet
      activation causes the liberation of sulphate conjugated CA (particularly DA) as
      well as free CA. The differences with regard to the collagen EC(50) values for
      free and sulphate conjugated CA release indicate that these species arise from
      different subcellular compartments.

PMID- 16793659
TI  - Multiple metabolic abnormalities in a patient with essential thrombocytosis.
AB  - A patient with extreme essential thrombocytosis who exhibited an array of real or
      spurious metabolic abnormalities is described. Careful venipuncture and prompt
      measurement avoided unnecessary further laboratory investigation and potentially
      dangerous overtreatment.

PMID- 16793661
TI  - The role of platelets in infective endocarditis.
AB  - There is growing evidence that platelets play an important role in the
      development of infective endocarditis (IE). This review focuses on interactions
      between bacteria and platelets. Many types of microorganism are capable of
      causing endocarditis. The oral streptococci, particularly Streptococcus sanguis
      and S. oralis, remain the most common causative bacteria in IE but Staphylococcus
      aureus is becoming an increasingly important agent. Several species of bacteria
      and fungi are able to cause platelet aggregation in vitro, and there are
      indications that this ability is associated with the production of severe
      disease. Different bacteria appear to utilise different mechanisms of
      aggregation, and mechanisms for adhesion may be distinct from those responsible
      for aggregation. At least one commonly studied strain of S. sanguis apparently
      utilises the host's IgG and complement responses to induce platelet activation.
      IE may therefore be among the number of diseases in which immunological
      activation of platelets is thought to be of importance. Other bacterial strains
      have their own adhesins and agonists. The more virulent bacteria, notably the
      staphylococci, also possess proteolytic enzymes and may directly activate
      coagulation pathways, whereas less virulent, opportunistic pathogens, such as
      some streptococci and Candida albicans, may rely on interactions with host
      factors for colonisation and proliferation. It is proposed that platelets are
      involved in formation of the non-bacterial thrombotic vegetation (NBTV) and are
      necessary for the effective adhesion of bacteria to the NBTV, and that platelets
      also influence the persistence and clinical outcome of the disease through
      proliferation of the thrombotic vegetation. It is hypothesised that successful
      colonisation of the heart valves by a micro-organism depends on effective
      adhesion of the bacteria or fungi to platelets, in combination with the ability
      to induce platelet activation and aggregation.

PMID- 16793662
TI  - Platelets and saphenous vein graft failure following coronary artery bypass
      surgery.

PMID- 16793663
TI  - Reversible and irreversible binding of fibrinogen to platelets.

PMID- 16793664
TI  - Biology of thrombopoiesis and the role of Mpl ligand in the production and
      function of platelets.

PMID- 16793665
TI  - Correlation between serum gamma-glutamyl transferase activity and the platelet
      count.
AB  - The serum gamma-glutamyl transferase (GGT) activity correlated significantly (P <
      0.008) with the platelet count in 55 patients with thrombocytosis. All patients
      were selected so as to have normal liver function tests(including serum GGT).
      This correlation was present in both genders and there was no significant
      correlation with the other liver function tests. These findings are additional
      evidence that platelets may contribute to the total serum GGT activity.

PMID- 16793666
TI  - Inhibition of the intimal hyperplasia in an arterial autograft model by blockade
      of the N-terminal of the integrin beta3 subunit by monoclonal antibody P37.
AB  - Myointima formation or intimal hyperplasia is a major undesirable problem at the
      anastomotic ends of narrow bore arterial autografts and in other arterial wall
      injuries, which often leads to late restenosis and thrombosis and whose
      pathogenesis is still not understood. Platelets are suspected to intervene at
      some stages of its development, together with endothelial and muscle cells, the
      extracellular matrix and, most probably, adhesion receptors. To ascertain whether
      and at what stage beta3 integrins are involved, a rat arterial autograft model
      was used, together with monoclonal antibody P37, which is directed to the
      sequence 101-109 of the beta3 subunit of the human platelet fibrinogen receptor
      (integrin alphaIIbbeta3) and inhibits platelet aggregation in vitro and acute
      thrombosis in vivo. Three groups of animals were used: group I underwent an
      arterial autograft of a 5-mm segment of the right common iliac artery; group II
      received, intravenously, a single dose (0.8 mg/kg) of P37 at 15 min before the
      graft implantation; and group III was treated as group II but a similar dose of
      antibody was additionally given on day 14 after the operation. Animals in each
      group were sacrificed on days 7, 14, 21, 30 and 50 after the operation, and the
      grafts were removed for light and electron microscopy observation and further
      time-dependent morphometric analysis. By day 14, group I autografts already
      showed intimal hyperplasia and secretory smooth muscle cells, while group II and
      II autografts presented only some degenerative changes in the medial layer, with
      no signs of hyperplasia. Intimal hyperplasia was observed on day 21 in group II
      and on day 30 in group III, although less pronounced than in the corresponding
      controls. However, by day 50, the three groups had the same thickness of
      myointima. The immunohistochemical determination of metalloproteases suggests no
      role for these enzymes in the immunoinhibition of myointima formation. We
      conclude that P37 inhibits the onset of the intimal hyperplasia in the arterial
      autografts and that this onset in treated animals seems to be related to the
      decay of the circulating antibody. Further work is required to decide whether a
      higher or longer presence of circulating P37 can definitively prevent the
      development of intimal hyperplasia, as well as to ascertain which cells and which
      beta3 integrin receptors intervene.

PMID- 16793667
TI  - Antithrombotic map of the N-terminal domain of the GPIIIa subunit of the human
      platelet fibrinogen receptor (GPIIb-IIIa) determined in vivo by monoclonal,
      immunochemical inhibition of acute arterial thrombosis.
AB  - The inhibition of the platelet fibrinogen receptor, the glycoprotein IIb-IIIa
      (GPIIb-IIIa) or integrin alphaIIbbeta3, has recently became an accepted practice
      in clinical cardiology. The interest lies now in the improvement of the
      antithrombotic activity and the minimization of the secondary effects of the
      receptor inhibitors, by their evaluation in vivo in the different dynamic
      conditions and pathological states under which these inhibitors have to perform.
      In this paper, we functionally map in vivo the N-terminal domain of the GPIIIa
      subunit, using the antithrombotic activity of five murine monoclonal antibodies
      (mabs) (P37, P40, 95-1, P95-2 and P97), all of them inhibitors of platelet
      aggregation in vitro and directed to this ligand binding domain of the human
      fibrinogen receptor. Competition experiments have shown that these mabs bind with
      high affinity (5-7 nM) and compete very strongly among themselves for binding to
      human resting platelets, except P40, which neither binds nor competes. These
      antibodies were assayed in a dog model of acute thrombosis in the carotid artery,
      which were induced 15 min after their intravenous administration (0.8 mg/kg). The
      antithrombotic activity was quantified by the measurement of the [111In]oxine
      labelled platelet deposition at the site of the arterial lesion and was expressed
      as the percentage of the total circulating platelets. Antibody P37, directed to
      the GPIIIa 101-109 sequence, decreased the platelet deposition 630-fold with
      respect to control animals. P95-2, P97 and P95-1 decreased the platelet
      deposition 160-, 32- and 25-fold, respectively, while P40, directed to the GPIIIa
      260-302 sequence, did not show any antithrombotic activity. We conclude that all
      the mabs directed to the N-terminal domain of GPIIIa, which inhibit platelet
      aggregation in vitro and whose epitopes are very close to each other and exposed
      in resting platelets, have high antithrombotic activity in vivo, which varies
      depending on the actual location of the epitopes in the receptor topography.
      Among these antibodies, P37, the strongest receptor inhibitor in vivo and whose
      epitope is most probably the closest to the fibrinogen binding site(s), seems the
      best candidate for comparative studies in animal models with today's best GPIIb
      IIIa inhibitors and for clinical trials in humans in order to arrest or prevent
      thrombosis, reocclusion and late restenosis.

PMID- 16793668
TI  - Cathepsin A-like activity is possibly the main acidic carboxypeptidase in human
      platelets.
AB  - Human platelets were investigated for activity of the acidic carboxypeptidases:
      cathepsin A, lysosomal carboxypeptidase B and prolyl-carboxypeptidase. It was
      found that the main acidic carboxypeptidase in human platelets had cathepsin A
      activity. No activity of lysosomal carboxypeptidase B and prolyl-carboxypeptidase
      in human platelets was detectable using their specific substrates. Human platelet
      cathepsin A-type enzyme hydrolyzed at the highest rate Cbz-Phe-Ala, Cbz-Phe-Met
      and Cbz-Phe-Leu, did not require sulfhydryl activator and was inhibited by serine
      protease inhibitors (DFP, DCI) and inhibitors that react with the SH group
      (mersalyl acid, PCMS, PCMB, HgCl2). Cbz-Phe-Ala and Cbz-Glu-Tyr were hydrolyzed
      at a broad pH range with optimum at pH 5.0-6.0. The chromatographic analysis on
      Con A-Sepharose and DEAE-Sephacel showed different forms of Cbz-Phe-Ala
      hydrolyzing enzyme in human platelets. The multiple forms of this enzyme were
      probably due to heterogeneity of carbohydrate moiety.

PMID- 16793669
TI  - Association of Br polymorphism of platelet GP Ia gene and immune thrombocytopenic
      purpura.
AB  - Studies on the molecular structure underlying Br(a)/Br(b) (HPA-5) platelet
      alloantigen show that a single base polymorphism at position 1648 on platelet
      mRNA coding for GP Ia results in a amino acid substitution at position 505 on the
      mature GP Ia which is associated with the two serologically defined Br types.
      While this polymorphism has no known effects on platelet function, the possible
      influence of this polymorphism in immune thrombocytopenia ITP is again
      unexplored. Therefore, the genotype frequency of Br polymorphism in ITP was
      compared with that of healthy general Korean population. Interestingly, there was
      a statistical difference (P=0.03) in genotype frequency of Br polymorphism. The
      association of Br(a)/Br(b) (HPA-5)genotype and occurrence of ITP may suggest the
      possible influence of genetic polymorphism on the pathogenesis of ITP.

PMID- 16793670
TI  - Platelet biotinylation for monitoring in vivo survival and cellular function.

PMID- 16793671
TI  - Reticulated platelets.
AB  - Young or reticulated platelets contain some residual mRNA, which is rapidly
      degraded after platelet release into the circulation. They can be easily detected
      either with supravital dye staining (e.g. new methylene blue) on blood films, or
      more commonly with fluorescent dyes (e.g thiazole orange) and flow cytometry.
      Using the latter technique many different groups have demonstrated that the
      measurement of reticulated platelets has much clinical potential. It is apparent
      that the level of reticulated platelets gives a relatively simple and non
      invasive measurement of the rate of thrombopoiesis in an analogous fashion to the
      red cell reticulocyte count. Many research groups are currently measuring
      reticulated platelets but with wide variation in data and methods. An
      international platelet panel has begun to develop protocols and between
      laboratory comparisons, which will result in the standardization of the
      procedure. Platelet reticulocyte analysis should thus become part of accepted
      haematological practice and provide useful clinical information for the
      investigation and monitoring of platelet production in various thrombocytopenic
      conditions. In particular, measurement of reticulated platelets will provide an
      excellent and simple means for monitoring the response of chemotherapy and
      transplant patients to growth factors (e.g. thrombopoietin) resulting in a
      decrease in the demand for platelet transfusion.

PMID- 16793672
TI  - Role of ADP and thromboxanes in human thrombus formation in ex vivo models.
AB  - Adenosine diphosphate (ADP) and prostaglandin derivatives play important roles in
      thrombogenesis. Their roles in platelet function have been extensively studied
      for more than three and two decades, respectively. Of further importance for
      thrombogenesis, and perhaps for atherogenesis as well, is that these compounds
      are involved in the regulation of vascular wall tone, both as constrictors and
      dilators. The aim of this brief essay is to highlight the relative importance of
      ADP and TxA(2) in collagen-induced thrombus formation at various well-defined
      shear conditions. To achieve this goal, we employed a human ex vivo model of
      thrombus formation, because well-defined and reproducible blood shear conditions
      are best created in such a device. The blood flow conditions varied from those
      encountered in healthy veins to vessels with severe atherosclerotic disease.
      These experiments were performed as parts of clinical phase I studies with novel
      antagonists of ADP- or TxA(2)-induced platelet aggregation. Probes for ADP and
      TxA(2) included the ADP receptor antagonist clopidogrel and the TxA(2) receptor
      antagonist linotroban, respectively. Their antithrombotic activities were
      compared with results obtained with the cyclo-oxygenase inhibitor aspirin. These
      studies demonstrated a significant effect of both ADP and TxA(2) on collagen
      induced ex vivo thrombus formation. Whereas ADP promoted platelet thrombus
      formation independently of the local shear, TxA(2) promoted platelet thrombus
      formation at high arterial shear only, and increasingly by increasing
      shear.However, at blood flow conditions triggering shear-induced platelet
      activation and aggregation, TxA(2) formation did not affect collagen-induced
      platelet thrombus formation since aspirin administration was insensitive to the
      thrombotic response. This contrasts with the need for ADP in shear-induced
      platelet aggregation. Thus, the function of ADP in human ex vivo platelet
      thrombus formation appears more global than the role of TxA(2). These
      observations are in agreement with recent published clinical findings.

PMID- 16793673
TI  - PMA induces platelet activation of specific antigens (CD62/CD63) in GpIIb-IIIa
      deficient platelets from Glanzmann's thrombasthenia.
AB  - Glanzmann's thrombasthenia (GT) is a hereditary platelet disorder resulting from
      a quantitative or qualitative deficiency of the major platelet membrane complex
      GPIIb-IIIa (CD41) required for platelet aggregation. We investigated by flow
      cytometry, the expression of CD41, fibrinogen, and of two platelet activation
      related antigens, CD62 and CD63, (i) before and after activation of platelets by
      PMA, and (ii) on the surface and within the cytoplasm of resting platelets, after
      permeabilization by saponin. Platelets from a series of normal subjects and from
      nine members of two GT families, were reacted with FITC-conjugated antibodies and
      analyzed on a flow cytometer. Fluorescence intensities measured on normal and GT
      platelets were quantified by using calibrated beads. Results showed lack of both
      GPIIb-IIIa and fibrinogen, on the platelet surface and also within the cytoplasm
      in five of these GT patients, whereas GPIIb-IIIa and fibrinogen remained normal
      in the four other cases. However, CD62 and CD63 antigenic levels were found
      within normal range for all members of these families, after PMA stimulation and
      also after platelet permeabilization. This work therefore showed that the lack of
      CD41 in GT, which causes strong disturbance of platelet aggregation, may not be
      associated with the deficiency of activation pathways.

PMID- 16793674
TI  - Effects of normal platelets on proliferation and constitutive cytokine secretion
      by human acute myelogenous leukaemia blasts.
AB  - The effects of soluble E-selectin, P-selectin and normal platelets on acute
      myelogenous leukaemia (AM L) blasts were investigated in vitro. We investigated
      effects on spontaneous and cytokine-dependent blast proliferation, and
      constitutive blast secretion of different cytokines. The presence of normal
      platelets during in vitro culture caused a dose-dependent increase in both
      spontaneous and cytokine-dependent AML blast proliferation. Addition of platelets
      also increased constitutive blast secretion of Interleukin 1beta (IL1beta ), IL6,
      GM-CSF and TNFalpha, whereas platelets had no effect on the release of IL1
      receptor antagonist. The effects of platelets on constitutive cytokine secretion
      were also detected when platelets and AML blasts were cultured in different
      chambers separated by a permeable membrane, and a further enhancement was
      achieved when blasts and platelets were cultured together. Soluble P-selectin had
      no effect on constitutive AML blast cytokine secretion or the platelet-induced
      enhancement of the secretion. However, both soluble E- and P-selectin altered AML
      blast proliferation for a minority of patients. We conclude that normal platelets
      can modulate the function of human AML blasts in vitro.

PMID- 16793675
TI  - Simultaneous detection of changes in cytoplasmic Ca(2+), aminophospholipid
      exposure and micro-vesiculation in activated platelets.
AB  - We have used flow cytometry to compare the temporal relationship between
      cytoplasmic Ca(2+)-fluxes and micro-vesiculation during platelet activation.
      Changes in fluorescence of the Ca(2+)-dye, fluo-3, and in forward light scatter
      as a measure of the decrease in platelet size that accompanies micro
      vesiculation, were assessed simultaneously. In other experiments, changes in
      Ca(2+) levels and aminophospholipid exposure were assessed using fura-red, which
      is a long wavelength range indicator, and FITC-annexin V. Results obtained using
      the ionophore A23 187 and the ATPase inhibitor, thapsigargin, showed that micro
      vesiculation is a relatively late event compared with intracellular Ca(2+)
      elevation. The relatively slow binding kinetics of annexin V prevented the
      establishment of a temporal relationship between increases in intracellular
      Ca(2+) and aminophospholipid exposure. Nevertheless, the combined use of fura-red
      and annexin V highlighted the heterogeneous response seen on some occasions with
      thapsigargin and always with a thrombin plus collagen mixture, and confirmed that
      individual platelets that bound annexin V were also those with elevated
      intracellular Ca(2+) levels.

PMID- 16793676
TI  - Platelet activation by mercuric compounds.
AB  - We previously showed that at low concentrations (0.01-10 micromol/l) mercury (Hg)
      compounds (especially methylmercuric chloride) may act synergistically with
      physiological agonists to activate platelets and may also cause changes in blood
      coagulation in experimental animals. Result obtained in this study indicate that
      the activation of pig blood platelets by methylmercuric chloride (MMC) is not
      dependent on membrane receptors for fibrinogen and ADP. Furthermore, we have
      calculated that pig platelets take up approximately 13-fold more Hg than plasma
      proteins during incubation of platelet-rich plasma with MMC. These findings may
      explain the recently reported link between vascular events and Hg poisoning.

PMID- 16793677
TI  - Formation of platelet-leukocyte conjugates in whole blood.
AB  - The purpose of this investigation was to obtain information on platelet-leukocyte
      conjugate formation in whole blood and on factors that affect it. We also
      measured platelet and leukocyte activation by quantitating the expression of
      CD62P and CD11b. In both cases a flow cytometric approach was used. The results
      show that platelet-monocyte and platelet-polymorphonuclear leukocyte (PMNL)
      conjugate formation is enhanced by simply stirring blood, with optimum conjugate
      formation occurring after 10 min. In the case of monocytes,conjugate formation
      was enhanced by adenosine diphosphate (ADP). Both monocyte and PMNL conjugate
      formation was enhanced by phorbol myristate acetate (PMA), but L-formyl methionyl
      lysyl proline (FMLP) was either without effect (monocytes) or inhibitory (PMNL).
      EDTA also inhibited conjugate formation (implying involvement of divalent
      cations), as did dextran sulphate (implying involvement of P-selectin = CD62P).
      Interestingly GR144053F, which acts at GpIIb-IIIa on platelets to interfere with
      fibrinogen binding, and also glycyl prolyl arginyl proline (GPRP), a peptide that
      interferes with the interaction between CD11c on leukocytes and fibrinogen, did
      not inhibit platelet-monocyte conjugate formation, but did inhibit the platelet
      PMNL interaction; this indicates that GpIIb-IIIa on platelets and CD11c on
      leukocytes and fibrinogen are involved in mediating the interaction between
      platelets and PMNL but not platelets and monocytes. Surprisingly arginyl-glycyl
      aspartyl serine (RGDS) inhibited the formation of both types of conjugate but
      this may be because it also inhibited both platelet and leukocyte activation as
      measured by CD62P and CD11b exposure and/or interferes with the binding of
      adhesion molecules other than fibrinogen. The results show that a flow cytometric
      procedure can be effective in obtaining rapid information on platelet-leukocyte
      conjugate formation in whole blood and on factors that are involved in its
      regulation. It is suggested that the technique may be applicable to the study of
      platelet-leukocyte conjugate formation in whole blood in disease, and also to
      study the effects of drugs interfering with conjugate formation.

PMID- 16793681
TI  - The biological basis of immune heparin-induced thrombocytopenia.
AB  - Heparin induced thrombocytopenia (HIT) remains the most severe adverse effect of
      heparin therapy. Recently, new information has been uncovered regarding the
      pathogenesis of this disorder. This review summarizes the clinical state,
      pathogenesis and diagnosis of HIT. It was stimulated by the recent recognition of
      heparin-platelet factor 4 (H.PF4) complexes as the major target antigen for
      heparin-dependent antibodies involved in this pathology. The formation of
      complexes between PF4 and heparin or other glycosaminoglycans, leading in some
      circumstances to the generation of antigenic structures reactive with HIT
      antibodies, is analysed. We also discuss how antibodies develop in heparin
      exposed patients and why these antibodies can become pathogenic only in some
      patients, while their presence remains asymptomatic in others. This review also
      focuses on the mechanisms that could be involved in the development of
      thrombocytopenia and thrombosis. This new understanding of HIT pathogenesis has
      permitted the introduction of new tools for retrospective or prospective
      diagnosis, and may provide new strategies for the avoidance or treatment of HIT
      and its complications.

PMID- 16793682
TI  - Lipoprotein (a) reduces platelet aggregation via apo(a)-mediated decreases in
      thromboxane A(2)production.
AB  - Agonist (collagen- or ADP-)-stimulated platelet aggregation and thromboxane B(2)
      (T X B(2) ) production was reduced in human whole blood (WB) and washed platelets
      (WP) that were co-incubated with lipoprotein (a)[Lp(a)] at levels of 25, 50 and
      100 mg % but not at 5 mg % relative to a baseline concentration of 1 mg %.
      Significant decreases in agonist-stimulated aggregation and T X B(2) levels were
      seen with 5, 25, 50 and 100 mg %purified apo (a) that was co-incubated with WB
      and WP relative to a baseline concentration of 1 mg %. Purified Lp(a) that was
      free of apo(a) [Lp(a)(-)], at concentrations of 5, 25, 50 and 100 mg %, that were
      co-incubated with WB and WP, had no impact on agonist-induced platelet
      aggregation and T X B(2) production relative to a baseline level of 1 mg %. A
      monoclonal antibody (Mab) (3B1) against apo(a) blocked Lp(a)-mediated reduction
      in platelet aggregation and T X B(2) concentrations in WB and WP that were
      stimulated by either agonist. Various Mabs against apoB failed to affect an Lp(a)
      induced reduction in WB and WP aggregation or T X B(2) levels in response to
      either agonist. These results strongly suggest that Lp(a)-induced decreases in
      collagen or ADP stimulated platelet aggregation and T X B(2) production are
      mediated by apo(a).

PMID- 16793683
TI  - Stimulation of phosphoinositide kinases by thrombin is restricted to the plasma
      membrane in platelets.
AB  - This study was based on the hypothesis that lipid kinases in the different
      subcellular fractions would be differently affected by thrombin-treatment of
      platelets prior to subcellular fractionation. When using our previously reported
      method for subcellular fractionation on Percoll self-generated gradients, marker
      enzymes were detected as previously described. Stimulation of intact platelets
      with thrombin induced increased activities of PtdIns 4-kinase, PtdIns(4)P 5
      kinase and PtdIns(4,5)P(2) 3-kinase in the plasma membrane fraction. PtdIns 4
      kinase was also detected in internal membranes but was not modified by thrombin.
      We conclude that the production of phosphoinositides phosphorylated on the D3 and
      D5 positions of the inositol ring is restricted to the plasma membrane and that
      only the enzymes that are present in, or relocated to, the plasma membrane when
      platelets are activated are stimulated by thrombin.

PMID- 16793684
TI  - The effect of PMA-induced differentiation on the surface expression of integrins
      on CHRF 288-11 megakaryoblastic cells in culture.
AB  - The integrins GPIIb-IIIa and alpha(v)beta(3) and the integrin subunits alpha(2) ,
      alpha(5) and beta(1) have been shown by flow cytometry to be present on the
      surface of CHRF 288-11 megakaryoblastic cells grown in culture. PMA-induced
      differentiation of these cells caused a rapid increase in the surface expression
      of alpha(v)beta(3), the vitronectin receptor, and a delayed decrease in surface
      expression of the alpha(5) subunit (presumably present as the alpha(5)beta(1)
      integrin of the fibronectin receptor). PMA caused no change in expression of
      GPIIb-IIIa, the alpha(2) subunit (presumably present as alpha(2)beta(1)) or of
      the beta(1) subunit overall. GPIIb-IIIa appeared to be present as an inactive
      complex on these cells.

PMID- 16793685
TI  - Platelet activation and serotonin release during colorectal surgery.
AB  - In vitro studies show serotonin has a profound vasospastic effect on human
      mesenteric arteries. A similar response has been shown in vivo in atherosclerotic
      primates. If platelet serotonin stores are released as a consequence of platelet
      activation during colorectal surgery, a similar effect may significantly alter
      the perfusion of newly formed anastomoses leading to ischaemia and anastomotic
      breakdown. Here we have studied the effects of surgery and anaesthesia on
      intraplatelet and plasma serotonin levels during the peri- and postoperative
      period following colorectal surgery. A series of six consecutive patients
      undergoing colorectal resection and anastomosis were selected. Peripheral venous
      blood samples, taken at specified times before and after surgery and prepared in
      a platelet stabilizing buffer solution, were analysed using a validated enzyme
      immunoassay technique. Intraplatelet serotonin levels were seen to fall post
      operatively, whilst plasma serotonin levels were shown to rise, implying
      significant platelet activation and serotonin during the peri-operative period.
      This study demonstrates the increased bioavailability of serotonin during the
      peri-operative period in colorectal surgery patients. If the in vitro effects of
      this amine are mirrored in vivo, increased plasma levels of serotonin may have an
      important role in anastomotic dehiscence secondary to ischaemia.

PMID- 16793686
TI  - Impaired platelet function in endotoxemic pigs analyzed by flow cytometry.
AB  - Endotoxin or bacterial lipopolysaccharide (LPS) is a structural component of Gram
      negative bacteria. It is believed to be the major pathogenic factor of Gram
      negative sepsis, and may result in intravascular coagulation and in a shock
      syndrome that is characterized by thrombocytopenia, leucopenia, hypotension,
      fever, reduced delivery of oxygen, metabolic acidosis and ultimately death. We
      have previously shown that both endotoxemic pigs and patients with Gram-negative
      sepsis have elevated levels of platelet microvesicles in their blood, which
      indicates platelet activation. In this study, we have used flow cytometry and
      fluorescein-labeled chicken anti-human fibrinogen to evaluate the in vivo effect
      of endotoxin on platelet function in a porcine model. Endotoxin infusion in pigs
      caused impaired platelet function when platelets were stimulated with adenosine
      diphosphate in vitro ( P < 0.001). We also found a similarly decreased platelet
      function in patients with Gram-negative sepsis. Since flow cytometry is a rapid
      method for determination of platelet function, this method may turn out to be a
      useful tool in clinical situations. Our results may contribute to our
      understanding of the bleeding problems that may occur in septic shock and in
      disseminated intravascular coagulation.

PMID- 16793687
TI  - Quantitation of megakaryocytopoiesis by computerized automatic in culture image
      analysis.
AB  - A computer-assisted automatic image procedure was karyocytopoiesis in culture.
      This analysis system was based on acetylcholinesterase staining, a specific
      staining for murine bone marrow megakaryocytes, and an image capturing instrument
      with a computer program. Two kinds of routine megakaryocyte culture methods were
      used, the plasma clot and the serum-free agar systems. A comparison between
      manual counting and the instrument was made. The image analysis software was able
      to distinguish between megakaryocytes (MK) at different stages of maturation. The
      results show that this analysis system can simultaneously detect not only the
      number of megakaryocytes and their colonies in each dish, but also the surface
      area of individual megakaryocytes. In addition, this analysis system functions
      automatically 24 hours a day and the results obtained are reproducible. Using
      this system, we have confirmed previous observations that thrombopoietin (TPO)
      and heparin stimulate both proliferation and maturation of megakaryocytes. In
      addition, we found that platelet factor 4 (PF-4) significantly reduced the number
      of megakaryocytes but not their cell surface area, whereas TGFbeta1 decreased
      both number and surface area of megakaryocytes, suggesting that PF4 and TGFbeta1
      negatively regulate megakaryocytopoiesis by different mechanisms. We noticed that
      megakaryocytes grown under agar culture conditions regularly had an increased
      size in comparison with those grown in a plasma clot system, which may be an
      indication that the plasma clot culture media contains an inhibitor(s) of
      megakaryocyte maturation. Our data indicate that this image analysis system, in
      addition to its automatic and reproducible features, is more efficient and allows
      detection of more parameters than routine manual microscopic detection.

PMID- 16793693
TI  - Distinct sequences of the glycoprotein Ib-binding domain of von Willebrand factor
      involved in shear induced platelet aggregation.
AB  - Shear-induced platelet aggregation (SIPA) requires von Willebrand factor (vWF)
      binding to the platelet receptors GPIb and alphaIIbbeta3. In order to determine
      the vW F sequences involved in SIPA at 4000/s, we studied the llb 3 effect of
      three monoclonal antibodies (mabs) 724, 713 and 328 to the A1 domain of vWF. We
      found that mab 724 induced an enhanced SIPA via a Fc gamma-receptor independent
      mechanism. In contrast, mab 713 and mab 328 could inhibit SIPA by 52 and 91% ,
      respectively. Based on distinct effects on SIPA, we can propose the following
      working model for the interaction between vWF and GPIb: mabs 713 and 328, which
      block SIPA, may recognize an epitope that is involved in binding to GPIb, whereas
      mab 724, which increases SIPA in the presence of vWF, may mimic the effect of
      botrocetin when binding to vWF, by inducing an active conformation of vWF, which
      may be more sensitive to high shear rate.

PMID- 16793688
TI  - Family screening for a Glanzmann's thrombasthenia mutation using PCR-SSCP.
AB  - Genetic counselling is often requested in Glanzmann's thrombasthenia, but
      measurements of GPIIb-IIIa density on platelets are often too inconclusive to
      allow a precise assessment of whether prospective parents are obligate
      heterozygotes for this disease by this measure alone. The recent application of
      PCR technology to Glanzmann's thrombasthenia has resulted in the identification
      of a large number of mutations, i.e. insertions/ deletions, splicing defects, in
      the genes for both GPIIb and GPIIIa. Among the reported abnormalities is an
      intronic G-->A substitution at the splice donor site of intron 15 in the GPIIb
      gene of a European gypsy tribe. This gives rise to an abnormal splicing, of an 8
      bp deletion located at the 3' end of exon 15, a reading-frame shift and a
      premature stop codon in the mRNA for GPIIb. In applying PCR-SSCP to the
      elucidation of the genetic defects of a series of Glanzmann's patients, we have
      found the above-cited abnormality in three more gypsy families in France. The
      presence of the mutation was initially established by sequencing the amplified
      fragment, and its presence in family members was confirmed by both PCR-SSCP and
      HphI restriction analysis. Evaluation of the intronic G-->A mutation enabled
      genetic counselling to prospective parents within these families.

PMID- 16793694
TI  - Von Willebrand factor, P-selectin and fibrinogen levels in patients with acute
      ischaemic and haemorrhagic stroke, and their relationship with stroke sub-type
      and functional outcome.
AB  - Although ischaemic stroke is associated with accentuated platelet function, it
      remains unclear whether this applies to all sub-types, especially lacunar
      infarcts, which differ from cortical infarction in their patho-aetiology.
      Similarly, conflicting evidence suggests that haemorrhagic stroke may, or may
      not, be associated with a hypothrombotic state. Levels of von Willebrand factor
      (vWF), fibrinogen, and P-selectin were measured within 48 h of ictus in 163
      patients with acute ischaemic stroke and 40 patients with acute primary
      intracerebral haemorrhage, and 33 age, gender and race matched-controls. vW F
      (IU/dl) was significantly increased in both cortical and lacunar ischaemic
      stroke, and haemorrhagic stroke, as compared with controls, median (semiquartile
      range): 158 (25) vs 144 (19) vs 147 (24) vs 114 (16), respectively. Similarly,
      fibrinogen (g/litre) was increased: 4.80 (0.90) vs 4.65 (0.70) vs 4.35 (0.83) vs
      3.70 (0.70). In contrast, soluble P-selectin (ng/ml) was increased in cortical
      stroke as compared with lacunar infraction patients or controls: 408 (101) vs 300
      (108) vs 324 (121), respectively; P-selectin was not increased in haemorrhagic
      stroke, 360 (153). Both vW F and fibrinogen correlated with 3-month functional
      outcome (modified Rankin score): r = 0.371 (2 P = 0.0006), and r = 0.195 (2 P =
      0.042), respectively; however, P-selectin was not associated with outcome: r =
      0.188 (2 P = 0.084). The results suggest that increases in vW F and fibrinogen in
      all types of stroke reflect an acute phase response; in contrast, increased
      soluble P-selectin levels in cortical stroke, but not lacunar infarction, suggest
      that platelets contribute to the patho-aetiology of some subtypes of ischaemic
      stroke.

PMID- 16793695
TI  - Hereditary defect of the platelet ADP receptor(s).
AB  - Four patients with a previously unrecognized congenital disorder of platelet
      function have recently been described. Their platelets aggregate very poorly to
      exogenous ADP. The abnormality is likely due to a severe defect of the platelet
      ADP receptor that is coupled to adenylate cyclase, as suggested by the following
      findings: 1) ADP does not normally lower cAMP levels of PGE1-treated platelets;
      2) platelet shape change induced by ADP is normal; 3) the binding of
      [radiolabelled]ADP to formalin-fixed platelets or of the ADP analogue
      [radiolabelled]2-MeS-ADP to fresh platelets is severely defective. Since all
      patients that have been described were born from consanguineous parents, the
      condition seems to be inherited as an autosomal recessive trait. Platelets of an
      obligate heterozygote have intermediate binding sites for 2-M eS-ADP, undergo a
      normal primary wave of aggregation induced by exogenous ADP, but do not normally
      secrete the content of their granules when stimulated by release-inducing
      agonists. Studies of normal platelets treated with acetylsalycilic acid revealed
      that ADP potentiates platelet secretion directly, and that the full complement of
      its platelet receptors appears to be necessary for this function.

PMID- 16793696
TI  - Snake venom C-type lectins as tools in platelet research.
AB  - The snake C-type lectins are a major group of proteins present in venoms that
      fold to a structure with similarities to classic C-type lectins. The loop that
      would be involved in calcium and sugar binding is truncated and heterodimers are
      linked by a disulphide bond and by swapping loop domains between the subunits. M
      any of these C-type lectins interact with platelet receptors to inhibit or induce
      platelet activation. The use of these C-type lectins to investigate platelet
      function is discussed and illustrated with specific examples.

PMID- 16793697
TI  - Flow cytometric analysis of agonist-induced annexin V, factor Va and factor Xa
      binding to human platelets.
AB  - Activated platelets provide a procoagulant surface for the assembly and
      expression of prothrombinase complex. Expression of activity is associated with
      the binding of the protease factor Xa (FXa) and the co-factor Va (FVa) to the
      procoagulant surface. A flow cytometric methodology to measure annexin V-FITC as
      well as FVa and FXa binding to ionophore A 23187 activated platelets is
      described. Annexin V-FITC was used to determine platelet exposure of
      phosphatidylserine. The binding was calcium-dependent and excess of unlabelled
      annexin V (10-fold) prevented the binding of the labelled protein. The binding of
      FVa and FXa to platelets was measured using specific FITC-labelled monoclonal
      antibodies. The FITC labelled antibodies were displaced by 10-to 20-fold excess
      of unlabelled antibodies. Binding was strictly Ca2+-dependent. Fixation of
      platelets by formaldehyde caused artificial binding of annexin V, FVa and FXa as
      well, irrespective of the platelet activation status. Using gel-filtered
      platelets, the binding of FVa increased with alpha -granule secretion but the
      amount of stored FVa was not sufficient to saturate the available platelet
      binding sites. Exogenous FVa was needed for maximal FVa binding to occur. No
      binding of FXa from internal platelet stores was observed. Addition of exogenous
      FVa and FXa resulted in FXa binding to the platelet surface. The methodology
      might be of use for the study of platelets from patients with bleeding disorders.

PMID- 16793698
TI  - Contribution of thromboxane and endomembrane Ca2+-ATPases to variability in Ca2+
      signalling of platelets from healthy volunteers.
AB  - Inter-individual variability in Ca2+ signal generation was studied in platelets
      from 15 healthy volunteers. The possible involvement of variation in thromboxane
      A production and variation in sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs)
      was investigated by using platelets isolated before and after intake of 500 mg
      aspirin, and by measuring the expression levels of two main SERCA isoforms (SERCA
      2b and PL/IM 430-recognizable SERCA). Considerable difference in Ca2+ responses
      were detected after platelet stimulation with thrombin, collagen or the SERCA-2b
      inhibitor, thapsigargin (TG), with inter-individual coefficients of variance of
      22-43% in the absence and 15-41% in the presence of aspirin. Differences in
      thromboxane A2 generation and SERCA expression contributed to this variability in
      various ways. In the absence of aspirin, the amount of formed thromboxane A2
      partially explains the level of the Ca2+ response induced by TG. On the other
      hand, in the absence of thromboxane-dependent effects, the expression levels of
      SERCA-2b and SERCA PL/IM 430 were inversely related to the responses evoked by
      collagen and TG, respectively. None of these factors were related to the level of
      the thrombin-evoked Ca2+ signal.

PMID- 16793699
TI  - Human platelets activation by convulxin is accompanied by tyrosyl-phosphorylation
      of PLCgamma2 and occurs independently of integrin alphaIIbbeta3.
AB  - In the present report we show that convulxin (Cvx), a C-type lectin from Crotalus
      durissus terrificus venom, induces platelet agregation and phospholipase C (PLC)
      activation by a protein tyrosine kinase (PTK)-dependent pathway. In addition, Cvx
      stimulates a rapid increase in tyrosine phosphorylation of human platelet
      proteins with molecular masses of 40, 72/74, 78/80 and 120 kDa, followed by
      dephosphorylation of some proteins. However, platelet aggregation was accompanied
      by the phosphorylation of a 105-kDa molecular mass protein. Furthermore, Cvx
      stimulates a rapid-tyrosyl phosphorylation of a 145-kDa protein that was
      identified as PLC gamma 2. Protein tyrose phosphatase (PTP) induced by Cvx was
      not blocked when platelets were stimulated in the presence of indomethacin,
      apyrase, EDTA or RGDS peptide, but inhibited by staurosporine and genistein.
      These results indicate that PTP is chronologically proximal to Cvx binding to
      platelets, and it is independent of platelet aggregation or fibrinogen binding to
      integrin alphaIIbbeta3. On the other hand, the phosphorylation step, and the
      phosphorylation of the 105-kDa protein, were both inhibited by RGDS and EDTA,
      which suggests that the integrin alphaIIbbeta3 beta is involved in these steps.
      Our results, taken together, show that Cvx induces platelet IIb 3 aggregation in
      a similar manner as collagen and collagen-related peptides that also trigger
      platelet aggregation by a PTK-dependent pathway, and stimulate tyrosyl
      phosphorylation of PLC gamma 2. However, Cvx is unique among platelet receptor
      agonists, because under test-tube stirring conditions it induces a PTP profile
      independently of integrin alphaIIbbeta3.

PMID- 16793700
TI  - Association of platelet function in hypertensive patients with left ventricular
      hypertrophy, transient myocardial ischemia, and coronary artery disease.
AB  - The aim of the study was to evaluate how platelet aggregation relates to left
      ventricular hypertrophy, presence of transient myocardial ischemia and coronary
      atherosclerosis in essential hypertensive patients. For that purpose platelet
      aggregation, symptom-limited treadmill-test, echocardiography and coronary
      angiography were performed in 65 male patients with uncomplicated essential
      hypertension. Aggregation was monitored both by a turbidometric method and by a
      method based on real-time estimation of mean aggregate size. Platelet function
      was also studied in 18 male normotensive subjects. Hypertensive patients with
      transient myocardial ischemia were characterized by increased platelet
      sensitivity to adenosine diphosphate, thromboxane A2 mimetic-U46619, serotonin,
      platelet activating factor and by increased spontaneous aggregability of
      platelets compared with normotensive subjects and to patients without myocardial
      ischemia. Platelet aggregation induced by low doses of agonists positively
      correlated with the degree of left ventricular hypertrophy. This study provides
      evidence that platelets play an important role in myocardial ischemia. Besides,
      it was found that platelet activity positively correlated with the degree of left
      ventricular hypertrophy. This may provide an additional link between left
      ventricular hypertrophy and coronary heart disease in hypertensive patients.

PMID- 16793701
TI  - Collagen binding induces changes in its platelet integrin receptor alpha2beta1.
AB  - Integrins can signal upon binding of their ligand, presumably because of
      conformational changes induced by ligand-binding. It has been postulated that
      ligand binding causes changes in the affinity of the integrin to its ligand. In
      order to test for ligand-induced change in the affinity of platelet alpha2beta1
      to collagen, labelled viable platelets were passaged through a column of
      fibrillar collagen and stringent lysis conditions were used to remove all low
      affinity receptors. A high-affinity fraction left on the collagen could be eluted
      with dithiothreitol (DTT) and 2% Sodium dodecyl sulfate (SDS). Antibodies raised
      against this fraction, identified alpha2beta1 by Western-blotting. Functional
      tests performed with the antibodies confirmed the involvement of the high
      affinity proteins in platelet-collagen interactions attributed to alpha2beta1:
      inhibition of collagen-specific platelet adhesion and aggregation. EDTA,
      chaotropic agents or low pH did not elute the high affinity fraction of
      alpha2beta1. However, DTT followed by acetic acid did, which indicates that the
      steps necessary to disrupt the high-affinity collagen alpha2beta1 bond are
      reduction of disulfide bond(s) followed by disruption of electrostatic
      interactions. Our data 2 1 suggest that (i) ligand binding induces the formation
      of a new disulfide bond in a fraction of alpha2beta1, (ii) that this bond is an
      intrareceptor, and (iii) that this change increases the affinity of the receptor
      to its ligand.

PMID- 16793702
TI  - Increased histamine content in Ca2+-ionophore A23187-activated human blood
      platelets.
AB  - Stimulation of human blood platelets with Ca2+-ionophore A23187 at the
      concentrations of 0.5, 1, 2 and 3 micromol/ litre increased the total platelet
      histamine content from 25 ng (resting platelets) to 35, 40, 42 and 47 ng/10(8)
      platelets, respectively. The maximum rise was 90% , while in the presence of
      thrombin (0.01-1 NIH U/ml) or phorbol 12-myristate 13-acetate (PMA) (10-100
      nmol/l) histamine content rose maximally by 40%. Ionophore induced a histamine
      increase in the same concentration range as that needed to induce platelet
      aggregation and liberation of [3H]-arachidonic acid. Decrease of temperature from
      37 to 0 degrees C or inhibitors of platelet functions, such as acetylsalicylic
      acid (1 mmol/litre) or [H1]-histamine receptor antagonist Dithiaden (0.1
      mmol/litre), 1 inhibited histamine liberation from A23187- stimulated platelets,
      but did not affect the total rise in histamine content. The presented results
      indicate that, similarly as with other stimuli, Ca2+-ionophore A23187 activation
      of human blood platelets is accompanied by histamine synthesis.

PMID- 16793703
TI  - Convulxin-induced platelet adhesion and aggregation: involvement of glycoproteins
      VI and IaIIa.
AB  - The interaction of convulxin (Cvx), a 72-kDa glycoprotein isolated from the venom
      of Crotalus durissus terrificus with human platelets has been studied. Cvx at low
      concentrations (below 100 pM) induced platelet aggregation, dense body secretion
      and intracellular calcium mobilization which indicates that Cvx is a potent
      activator of human platelets. Cvx-induced platelet aggregation and secretion was
      inhibited by 6Fl an anti-integrin alpha2beta1 monoclonal antibody that was
      without effect on calcium mobilization. Anti-GPVI Fab fragments inhibited
      aggregation, secretion and calcium mobilization triggered by Cvx. In addition,
      immobilized Cvx was found to induce divalent cation-independent platelet adhesion
      in a static system. Platelet adhesion to Cvx was inhibited by anti-GPVI Fab
      fragments but not by anti-integrin alpha2beta1 . Cvx was shown to bind to a
      57,000 Dalton protein that was identified as GPVI. Altogether, these results
      indicate that GPVI behaves as a receptor for Cvx, while integrin alpha2beta1
      could play a regulatory role in Cvx-induced platelet aggregation. Cvx and
      collagen interaction with platelets, thus appears to share some characteristics
      but to also have specific properties.

PMID- 16793704
TI  - Hydrogen peroxide formation in platelets of patients with non-insulin-dependent
      diabetes mellitus.
AB  - A group of 29 patients with non-insulin-dependent diabetes mellitus (NIDDM) was
      compared with a group of 19 patients who had good glycemic control for platelet
      activity and hydrogen peroxide formation. NIDDM patients showed platelet
      hyperactivity in response to low ADP concentrations. In addition, stimulated
      platelets from untreated NIDDM patients produced more hydrogen peroxide than
      platelets of treated and normal subjects. Hydrogen peroxide accumulation was not
      related to modification of the enzymatic systems involved in its synthesis and
      break-down. The specific activities of NAD(P)H cytochrome C reductase, catalase,
      glutathione peroxidase and glutathione reductase were not different between
      patients and healthy subjects. It is likely that the platelet intracellular
      elevation of reactive oxygen free-radicals could play an important role in the
      vascular complications and thrombotic risk that is often present in NIDDM
      patients.

PMID- 16793705
TI  - Activation of leukocytes in whole blood samples by N-formyl-methionyl-leucyl
      phenylalanine (FMLP) enhances platelet aggregability but not platelet P-selectin
      exposure and adhesion to leukocytes.
AB  - Adhesion of platelets to neutrophils and monocytes is believed to play an
      important role in intercellular communication. Evidence has been provided that
      such heterotypic cell-cell contacts via adhesion molecules may be directly
      involved in intercellular signal transduction as well as facilitate the action of
      soluble signal transmitters, e.g. cathepsin G, PAF or nitric oxide. With respect
      to platelet activation, stimulatory and inhibitory effects of leukocytes have
      been reported, and the results obtained seem to be influenced by the experimental
      conditions. We investigated the effect of leukocyte stimulation on platelet
      behaviour in samples of human citrated whole blood. Adding the chemotactic
      peptide FM LP, which stimulates neutrophils and monocytes but not lymphocytes and
      platelets, to stirred whole blood samples resulted in a significant enhancement (
      P < 0.01) of spontaneous as well as ADP-induced platelet aggregation (25 vs 33%
      and 66 vs 69% , respectively). In contrast stirring-induced as well as ADP
      induced increase of P-selectin exposure (33 and 107% , respectively) was not
      affected by FMLP. In unstirred whole blood samples, about 10 to 20% of
      neutrophils and monocytes had bound platelets to their surfaces, and the number
      of these heterotypic conjugates was enhanced about twofold during spontaneous
      platelet aggregation. Addition of FMLP significantly reduced the stirring-induced
      formation of platelet-neutrophil conjugates but not of platelet-monocyte
      conjugates. These results indicate that neutrophil and/or monocyte activation in
      whole blood may enhance platelet aggregation, but not secretion (CD62P exposure)
      and formation of heterotypic platelet-leukocyte conjugates.

PMID- 16793706
TI  - Impaired platelet function correlates with multi-organ dysfunction. A study of
      patients with sepsis.
AB  - Patients with sepsis often suffer from haemostatic disturbances such as
      haemorrhage and disseminated intravascular coagulation (DIC). Considering the
      pivotal role of platelets in haemostasis, we have investigated platelet function
      by flow cytometry in 16 patients with sepsis for a better understanding of their
      haemostatic function. We have also investigated whether platelet function
      correlates with the severity of disease assessed by multiple organ dysfunction
      (MOD) score and patient outcome. The platelet response ex vivo after stimulation
      with agonists, measured as platelet fibrinogen, binding was low in comparison
      with healthy volunteers ( n = 30). This could reflect a previous response to
      agonists in vivo , which lead to platelet activation and consumption and
      formation of microthrombi that could then participate in the development of M OD.
      The platelets that remain in the circulation might be the result of a selection
      process where the most active platelets have already been consumed, and the
      remaining population consists of less active platelets. Another explanation might
      be desensitization of the remaining platelets because of exposure to agonists in
      vivo . Platelet activation with the agonists ADP and arachidonic acid were
      predictive of subsequent development of MOD and final patient outcome.

PMID- 16793707
TI  - GPIIb-IIIa antagonists cause rapid disaggregation of platelets pre-treated with
      cytochalasin D. Evidence that the stability of platelet aggregates depends on
      normal cytoskeletal assembly.
AB  - Platelet activation is accompanied by changes in the composition of the platelet
      cytoskeleton with rapid incorporation and displacement of certain proteins. Here
      we have inhibited cytoskeletal assembly by pretreating platelets with
      cytochalasin D (CyD) and investigated the effect on the stability of the
      aggregates that form. The experiments were performed in both citrated and
      hirudinized platelet-rich plasma (PRP) and aggregation was induced by adenosine
      diphosphate (ADP), collagen, the TXA2-mimetic U46619 and adrenaline. Platelets in
      the aggregates that formed, underwent rapid disaggregation on addition of EDTA or
      a GpIIb-IIIa antagonist such as MK-852 and GR144053F, all of which are agents
      that interfere with the ability of fibrinogen to interact with GpIIb-IIIa. This
      was the case irrespective of the aggregating agent used and occurred in both
      citrated and hirudinized PRP. In contrast, the rate of disaggregation brought
      about by some other agents, iloprost and ARL 66096, appeared to be unaffected by
      CyD. Information was also obtained on the effects of CyD on the cytoskeletal
      changes brought about by ADP and the effects on the cytoskeleton of subsequent
      addition of M K-852. The results show that CyD retards the incorporation of
      certain proteins (actin, myosin, alpha -actinin, actin binding protein and a 66 K
      protein) into the cytoskeleton and that subsequent addition of MK-852 results in
      rapid displacement of some of these with re-incorporation of a 31 K protein. The
      results suggest that the early changes in the cytoskeleton following platelet
      activation contribute to the stability of the aggregates that form, and that
      interference with these early changes results in aggregates that are easily
      disassembled by agents that interfere with GpIIb-IIIa-fibrinogen complex
      formation.

PMID- 16793708
TI  - Increased platelet activation and decreased fibrinolysis in the pathogenesis of
      aseptic necrosis of the femoral head.
AB  - Thrombotic events, increased tendency toward intravascular thrombosis and
      decreased fibrinolysis seem to be possible pathologic causes for aseptic necrosis
      of the femoral head (ANFH) in adults. This project was to study whether either
      increased platelet activation or decreased fibrinolytic activity and/or any other
      thrombogenic factor may be implicated in the evolvement of ANFH. The speed of the
      in vitro lysis was significantly lower in patients (both in primary and in
      secondary cases) compared with healthy controls. The platelet activation
      (measuring with beta TG) proved to be significantly higher in the primary group
      as well as in the secondary group compared with healthy controls. Lp(a) levels
      were elevated in primary and secondary cases. This alteration was more
      characteristic in the primary cases. Fibrinogen levels were also elevated in the
      primary group, but the difference was not significant. The data shown here may
      further support that hypofibrinolysis and increased thrombogenesis are major
      causes of ANFH. Early diagnosis of ANFH increases the chances of modifying the
      course of this disabling disease.

PMID- 16793709
TI  - Platelet activation in diabetic microangiopathy.
AB  - Platelet activation and hyperreactivity are known to be associated with a rapid
      development and progression of diabetic angiopathy. The present study attempts to
      clarify whether IDDM patients without diabetic complications have an increased
      platelet activation and whether in vivo platelet activation is altered in the
      presence of diabetic microangiopathy. Platelet activation was assessed by flow
      cytometry analysis in 50 healthy controls (c) and in 41 patients with insulin
      dependent diabetes mellitus (IDDM type 1) who were screened for diabetic
      complications. Sixteen of these patients (0) showed no evidence of
      microangiopathic organ lesions as assessed by an established standard battery of
      clinical tests, whereas the other 25 patients had diabetes derived microvascular
      complications (dmc). Patients with macroangiopathy were ruled out. Platelet
      activation was evaluated by flow cytometric detection of four activation
      dependent platelet surface markers (lysosomal GP53, thrombospondin, P-selectin
      and ligand-induced binding site-1 of GPIIb-IIIa). A higher percentage of
      thrombospondin-positive platelets was detected in the IDDM patients without
      complications: 8.6 +/- 0.9% (0) vs 6.1 +/- 0.4% (c) vs 5.4 +/- 0.4% (dmc), P <
      0.05, respectively. A decrease in GP53-, P-selectin-, and LIBS-1-positive
      platelets was observed in the IDDM group with dmc: for GP53 17.4 +/- 1.0% (dmc)
      vs 23.4 +/- 1.0% (c), P < 0.05; for P-selectin 5.5 +/- 0.6% (dmc) vs 8.0+/-0.7%
      (c), P < 0.01 and for LIBS-1 8.3 +/- 0.9% (dmc) vs 15.8 +/- 1.3% (c), P < 0.01.
      No differences in these markers were found in controls and IDDM patients without
      complications. In addition, no correlations were found between the glucose
      metabolism and platelet activation. These findings indicate (i) that the platelet
      system is pre-activated in IDDM , and (ii) that an increased consumption of
      activated platelet may occur in the vessels of IDDM patients with diabetic
      microangiopathy.

PMID- 16793710
TI  - Spreading of platelets: a morphological marker for platelet reactivity in
      peripheral arterial occlusive disease.
AB  - Platelet-surface contact is the first step in thrombus formation. Platelet
      spreading makes this initial contact irreversible. On the other hand plasma
      lipids and fibrinogen have been described to activate platelets or promote
      adhesion. We therefore investigated whether platelet spreading under stagnation
      point flow conditions correlated with plasma concentrations of cardiovascular
      risk factors such as fibrinogen and high density lipoprotein (HDL)-cholesterol.
      Platelet rich plasma (PRP) from patients with peripheral arterial occlusive
      disease and healthy controls was examined by means of the Stagnation-Point Flow
      Adhesio- Aggregometer (SPAA). The SPAA comprises a microscopic setup with a flow
      chamber that permits direct observation and quantitation of platelet deposition
      onto standardized surfaces. After the flow experiments the deposited platelets
      were analyzed morphometrically for the degree of spreading expressed as inverse
      circularity (1/C). 1/C was correlated over 2 X 2 tables of fibrinogen combined
      with plasma levels of HDL-cholesterol, each of which was divided into a low and
      high value group. The patient and control group differed significantly with
      regard to 1/C, i.e. patient platelets demonstrated more adhesive platelets with a
      more extensive degree of spreading. 1/C was inversely correlated with HDL
      cholesterol and showed significant differences between the patient and the
      control group. Increased 1/C values were found when associated with high
      fibrinogen levels and simultaneously with low HDL-cholesterol concentrations.
      Platelet spreading shows a correlation with increased levels of independent
      plasmatic risk factors for thrombosis in PAOD patients. Obtained during
      stagnation-point flow, spreading seems to be a morphological marker for platelet
      hyperreactivity.

PMID- 16793711
TI  - Role of GPIIb-IIIa in platelet-monocyte and platelet-neutrophil conjugate
      formation in whole blood.
AB  - Platelets in stirred whole blood can be induced to form aggregates and also to
      form heterotypic platelet-monocyte (P/M) and platelet-neutrophil (P/N)
      conjugates. Here we have investigated the effects of three GPIIb-IIIa antagonists
      (GR144053F, MK-852 and Reopro, a CD62P-blocking antibody, GA6, and EDTA on the
      conjugate formation that occurs on stirring whole blood and in response to adding
      ADP and PAF. We have confirmed the identities of the conjugates by light
      microscopy after cell sorting. Platelet aggregation was measured by platelet
      counting. Monocytes, neutrophils, P/M and P/N were detected and quantitated using
      immunofluorescence and flow cytometry. Stirring whole blood resulted in both
      platelet aggregation and formation of P/M but not P/N. Adding ADP or PAF to whole
      blood caused rapid platelet aggregation and generation of both P/M and P/N. All
      of the GPIIb-IIIa antagonists studied had similar effects: inhibition of stirring
      induced platelet aggregation and P/M formation, and inhibition of ADP-induced
      platelet aggregation and P/N formation. In contrast, they accelerated ADP induced
      P/M conjugate formation and PAF-induced formation of both P/M and P/N. Both EDTA
      and GA6 completely inhibited P/M and P/N, which is commensurate with CD62P being
      involved in platelet-leucocyte conjugate formation. The results of these
      investigations suggest that GPIIb-IIIa has a dual role in determining the
      interaction between platelets and leukocytes.

PMID- 16793712
TI  - Clopidogrel: a review of its mechanism of action.
AB  - The search for active antiplatelet drugs within the original chemical class of
      the thienopyridines, led to the discovery of clopidogrel, a novel ADP-selective
      agent whose antiaggregating properties are several times higher than those of
      ticlopidine. The antiaggregating properties of this compound are well known and,
      very recently, new results have clarified its mechanism of action. Clopidogrel is
      active only after intravenous or oral administration, and no circulating activity
      has been found in the plasma of treated animals or human volunteers. Experiments
      in rats have demonstrated that the antiaggregating activity was caused by a
      shortlasting metabolite generated in the liver by a cytochrome P450-dependent
      pathway. The antiaggregating property of clopidogrel is caused by an inhibition
      of the binding of ADP to its platelet receptors, and more specifically to the low
      affinity receptors, the high affinity binding sites being unaffected by
      clopidogrel. Several events in the ADP activation process, including adenylyl
      cyclase down-regulation, protein tyrosine phosphorylation, activation of the
      GPIIb-IIIa complex, fibrinogen binding, aggregation and release, were inhibited
      by clopidogrel and indicate their close relationship with the activation of a low
      affinity receptor by ADP. In contrast, binding of ADP to its high affinity
      binding sites (clopidogrel-resistant receptors) induced shape change, cytosolic
      calcium increase and phosphorylations of several other proteins, some events
      which were clopidogrel-sensitive. Thus, clopidogrel not only constitutes a potent
      antithrombotic drug in humans but also a good tool to study the effect of ADP on
      platelets.

PMID- 16793713
TI  - Increased in vivo platelet activation and reduced intravascular endothelium
      derived relaxing factor and nitrate/nitrite production in patients with insulin
      dependent diabetes mellitus.
AB  - Limited information seems to be available about the role of reduced endothelial
      production of endotheliumderived relaxing factor (EDRF)-nitrate/nitrite (NO) in
      the pathogenesis of diabetic angiopathy in insulindependent diabetes. A report of
      urinary and serum nitrate/nitrite, glucometabolic parameters, endothelial and in
      vivo platelet activation markers of 22 insulin dependent diabetics (IDDM)
      patients are given. Urinary and serum nitrate/nitrite concentrations were reduced
      in IDDM. This was independent of disease duration, presence of angiopathy and the
      glucometabolic parameters. A significant and inverse correlation of
      nitrate/nitrite excretion with endothelial markers (von Willebrand factor,
      soluble thrombomodulin) was documented. Moreover, reduced nitrate/nitrite
      excretion was strongly associated with elevated plasmatic beta -thromboglobulin
      levels. EDRF-NO production is reduced in IDDM and this reduction correlates with
      endothelial damage. Decreased nitrate/nitrite excretion may also influence in
      vivo platelet function, which results in increased in vivo platelet activation
      and suggests that the reduced intravascular production of EDRF-NO might play a
      role in the pathogenesis of angiopathy in IDDM.

PMID- 16793714
TI  - Measurement of platelet activation and adhesion to leukocytes during
      haemodialysis.
AB  - In this study we used fluorescent-labelled antibodies to measure the extent of
      platelet adhesion to polymorphonuclear leukocytes (PMNLs), monocytes and
      lymphocytes. The activation of platelets, PMNLs and monocytes were also measured
      during the course of haemodialysis treatment using flow cytometric techniques
      established in our laboratory. Twenty patients were treated with either a
      cellulose membrane (TFU) or a polycarbonate filter (Pro 500). Blood samples were
      taken from the output line of the dialyser 2, 15, 30 and 180 min after commencing
      dialysis and just before starting treatment. Compared with the pre-dialysis
      sample, there was a marked increase in platelet-PMNL conjugate formation at 2
      min, followed by a decrease in conjugates at 15 and 30 min, and a slight increase
      at 180 min. During extracorporeal circulation PMNLs become activated as measured
      by a CD11b upregulation at 15, 30 and 180 min, but not at 2 min. Platelet binding
      to monocytes was increased above 15 min after starting dialysis, and monocyte
      activation was slightly increased above basal levels during the same period. The
      activation state of circulating free platelets, as measured by surface P-selectin
      exposition, initially decreased slightly, but then returned to basal levels over
      the 3-h period. Changes in cell counts were also detected: there was a massive
      decrease in circulating PMNLs and monocytes, and a small decrease in circulating
      platelets, at 15 and 30 min. These reverted to basal values by the end of the 3-h
      period. There was no change in the number of circulating lymphocytes or
      erythrocytes. These results show that flow cytometric studies on whole blood
      samples may provide important information on the behaviour of circulating blood
      cells, which could supplement conventional clinical measurements, to give a
      better insight into changes that occur in the circulation during haemodialysis.

PMID- 16793715
TI  - Effect of ciprofibrate on platelet aggregation in patients with combined
      hyperlipidemia.
AB  - This study was designed to investigate the effect of ciprofibrate on platelet
      aggregation in patients with combined hyperlipidaemia. Platelet aggregation
      measurements in platelet-rich plasma were carried out in 30 patients using the
      Biola 230 LA platelet aggregation analyser before treatment, 4 weeks and 8 weeks
      after ciprofibrate (100 mg/day) therapy. A control group consisted of 37 healthy
      subjects. We found that spontaneous and 0.25 microM ADP-induced platelet
      aggregation were significantly decreased after 4-weeks of therapy, from 4.6 to
      3.2% and from 11.3 to 7.6% , respectively. However, there was no difference 8
      weeks after the treatment onset. Platelet aggregation induced by adrenaline was
      unchanged during the ciprofibrate therapy.

PMID- 16793717
TI  - Functional characterization of platelet ADP receptors.

PMID- 16793716
TI  - Oxidized low density lipoprotein (LDL) and platelet intracellular calcium:
      interaction with nitric oxide.
AB  - The present study tested the effects of ox-low density lipoprotein (LDL) on
      nitric oxide (NO)-dependent decrease in agonist-stimulated [Ca2+]i. The effects
      of ox-LDL on platelet aggregation were also evaluated. Platelets loaded with FURA
      2 AM (2 micromol/litre) were incubated with NO-donors for 2-10 min to obtain a 40
      50% reduction in ?[Ca2+]i and with NO-donors plus ox-LDL (100 microg of
      protein/ml). Thrombin (0.03 U/ml) was used as an agonist. In some experiments 8
      Br-cGMP (0.5-1 mmol/l) was used to investigate the NO-dependent intraplatelet
      signalling system. Slightly oxidized LDL was obtained by leaving native LDL in
      the light at room temperature for at least 7 days. Ox-LDL did not cause any
      increase in thrombin-induced [Ca2+] (control: 215.4 +/- 44.3 nmol/l, ox-LDL 223.4
      +/- 35.3 nmol/l, M +/- SEM; n = 8) and platelet aggregation (control: 78.7 +/-
      4.9% , ox-LDL: 78.9 +/- 4.2% , n = 12). Ox-LDL antagonized the effects of NO
      donors on platelet [Ca2+]i (NO-donor: 137.4 +/- 22.1 nmol/l, NO + ox-LDL: 177.3
      +/- 27.6 nmol/l, n = 11; P < 0.001) and platelet aggregation (NO-donor: 15.4 +/-
      3.4% , NO + ox-LDL: 28.9 +/- 3.8%, n = 24; P < 0.001). Ox-LDL did not affect the
      inhibitory activities of 8-Br-cGMP on platelet aggregation (8-Br-cGMP: 22.0 +/-
      8.5%, 8-Br-cGMP + ox-LDL: 19.3 +/- 7.8%, n = 5) and platelet [Ca2+]i . In
      conclusion, slightly oxidized LDL does not directly activate platelets and does
      not i affect the intracellular NO-dependent signalling system. The present
      results suggest that LDL reduces the antiplatelet activity of NO mainly by
      preventing its biological effects.

PMID- 16793718
TI  - Effects of acute myelogenous leukemia blasts on platelet release of soluble P
      selectin and platelet-derived growth factor.
AB  - Complex interactions occur between platelets and normal as well as leukemic
      myeloid cells. In vitro co-culture of platelets and acute myelogenous leukemia
      (AML) blasts with allogeneic platelets enhances blast proliferation and
      constitutive cytokine secretion. In the present study the effects of AML blasts
      on the platelet release of soluble mediators are characterized. Normal platelets
      released soluble (s) P-selectin and platelet-derived growth factor (PDGF), both
      when cultured alone and in the presence of AML blasts, and for certain patients
      the presence of AML blasts increased the platelet release of these mediators.
      Addition of exogenous interleukin (IL) 10 to platelet-AML blast cultures further
      increased platelet release of PDGF and sP-selectin. For certain patients
      decreased AML blast cytokine secretion was observed when PDGF-specific antibodies
      were added to cultures with blasts plus platelets, these results indicate that
      platelet release of PDGF is a molecular mechanism for the enhancement of AML
      blast cytokine secretion. We conclude that complex functional alterations are
      induced both in AML blasts and normal allogeneic platelets during in vitro co
      culture of leukemia cells and platelets.

PMID- 16793719
TI  - The relationship between mean platelet volume, stroke subtype and clinical
      outcome.
AB  - Platelets play a crucial role in the pathophysiology of atherothrombotic disease
      and are involved in the early thromboembolic phase of ischaemic stroke. Large
      platelets are known to be more active. We hypothesized that thrombomegaly would
      be limited to patients with cortical infarction as compared with patients with
      lacunar infarcts, and that it would be associated with functional outcome. Mean
      platelet volume (MPV) and platelet count (PC) were studied in 167 hospitalized
      patients with stroke within 48 h of symptom onset, and 65 age, gender and race
      matched controls. Stroke was clinically and radiologically sub-typed. MPV was
      significantly higher in patients with ischaemic stroke than the control group:
      mean (SD) 7.35 (1.05) vs 7.09 (0.74) fl, 2 P = 0.04; this difference could be
      explained by MPV being higher in patients with cortical stroke: 7.46 (1.00) fl, 2
      P = 0.039, but not lacunar infarction: 7.14 (1.16) fl, 2 P = 1.0. No difference
      was seen in PC between ischaemic patients and controls: 231 (82) 10(9)/l vs 236
      (54) 10(9)/l, 2 P = 0.63. MPV did not change at 3 months post-stroke in surviving
      patients with ischaemic stroke: 7.39 (1.03) fl vs 7.34 (0.97) fl, 2 P = 0.53.
      Patients who were dead or dependent at 3 months had a significantly higher
      baseline MPV and a tendency to a lower PC than those who returned to
      independence. MPV and PC were not altered in patients with primary intracerebral
      haemorrhage. No differences in red cell volume was observed. Platelet volume is
      elevated in acute ischaemic stroke, a finding that persists at 3 months post
      stroke and is limited to patients with cortical infarction. Thrombomegaly is a
      risk factor for a poor outcome after ischaemic stroke.

PMID- 16793721
TI  - Identification of new and known polymorphisms in glycoprotein IIb and IIIa genes
      by denaturing gradient gel electrophoresis.
AB  - Glycoprotein IIb and IIIa contain antigenic determinants involved in the
      potential production of allo- or autoantibodies directed against platelets, that
      may result in severe thrombocytopenia. Most of these epitopes appear to be
      supported by single nucleotide substitutions. We have used denaturing gradient
      gel electrophoresis (DGGE) to identify sequence variations within the promoter
      and the coding regions of the glycoprotein IIb and glycoprotein IIIa genes. Using
      genomic DNA from 60 unrelated normal individuals, we have amplified short domains
      that encompass the coding sequences and the exon-intron boundaries of both genes
      that were further separated according to their melting behaviour during the
      denaturant electrophoretic migration. Only the fragments with an abnormal
      migration pattern were sequenced. We confirmed the sensitivity of this method by
      recognizing both previously described Human Platelet Antigen polymorphisms and
      mutations affecting either the glycoprotein IIb or the glycoprotein IIIa genes in
      thrombasthenic patients. We also identified four other polymorphisms. Two were
      located in the glycoprotein IIb gene, involving intron 21 (C<-->G at nucleotide
      10480) and first codon of exon 30 (codon GTC<-->GTT coding for residue Val 990),
      and two in the glycoprotein IIIa gene (exon 6 CCC<-->CCT coding for residue Pro
      268; intron 14 C<--> T at position 37126). The screening of the GPIIIa promoter
      also revealed three different polymorphisms located at position-468 (A/T
      polymorphism), -425 (A/C polymorphism) and-400 (A/C polymorphism), which could
      influence the expression of the complex at the cell surface. Denaturing gradient
      gel electrophoresis appears to be a sensitive and specific technique for
      identifying polymorphisms and mutations in the GPIIb and GPIIIa genes.

PMID- 16793720
TI  - Distinct cholesterol and phospholipid incorporation at the platelet plasma
      membrane of hyperlipidemic subjects: structural order and function.
AB  - Plasma lipid composition, platelet aggregation, cholesterol (Ch)/glycoprotein IIb
      IIIa (GP) and phospholipid (Ph)/GP molar ratios, fatty acid composition and
      structural order (1, 6-diphenyl-1, 3, 5-hexatriene (DPH) fluorescence anisotropy
      at 35 degrees C (r(DPH,35)) of human platelet plasma membranes (HPPM) were
      measured in four DPH,35 groups of hyperlipidemic patients (II: plasma Ch < 250
      mg/dl and TG (triglycerides) <220 mg/dl, n = 21; III: Ch > 250 mg/dl and TG < 220
      mg/dl, n = 23; IV: Ch < 250 mg/dl and TG > 220 mg/dl, n = 18; and V: Ch > 250
      mg/dl and TG > 220 mg/dl, n = 12) and compared with those of the control group
      (I). Our results were: (i) in groups III, IV and V the HPPM (Ch + Ph)/GP molar
      ratio increased 7.0+/-7.7% (mean SD); (ii) the Ph/GP molar ratio increased
      significantly in groups III, IV and V, but most in IV and V, while the Ch/GP
      molar ratio increased only in groups III and V; (iii) the mean relative increase
      of Ch with respect to Ph in the HPPM of groups III, IV and V was 140% 21% and
      54%, respectively; (iv) the Ch/GP molar ratio was correlated with LDL-Ch (0.41+/
      0.16, P < 0.002, n = 55, for all the subjects and 0.60+/-0.11, P < 2.10(-4), n =
      33, for subjects with TG < 220 mg/dl), however, it was totally uncorrelated with
      HDL-Ch; (v) the HPPM Ch/Ph molar ratio was positively correlated with plasma Ch
      (r = 0.51+/-0.08, P < 1.10(-6), n = 83) and with (LDL + HDL) Ch (r = 0.64+/-0.07,
      P < 1.10(-6), n = 73), the former correlation increased significantly ( r =
      0.67+/-0.07, P < 1.10(-6), n = 53) when done only for subjects with TG < 220
      mg/dl; (vi) the Ch/Ph molar ratio was only increased in group III (0.70+/-0.03, P
      < 3.10(-5), n = 23) and decreased in group IV (0.62+/-0.02, P < 0.001, n = 18);
      (vii) the fatty acid/GP molar ratio was significantly increased in groups IV and
      V, however, a significant absolute and relative increase of C16:0 and C18:1 was
      observed only in severe hypertriglyceridemia (> 500 mg/dl), together with a
      relative decrease of C18:0 and C20:4 ( n - 6); (viii) the HPPM structural order,
      as probed by r(DPH,35), was negatively correlated with DPH,35 plasma TG (r =-
      0.61+/-0.10, P < 4.10(-5), n = 39), the Ph/GP molar ratio (r =-0.58+/-0.10, P <
      2.10(-4), n = 39) and the the (C18:1 + C18:2))/GP molar ratio (r =- 0.80+/-0.05,
      P < 1.10(-6), n = 39), however, it was independent of plasma and HPPM Ch; (ix)
      the higher HPPM Ch/Ph molar ratio in group III was associated (r = 0.58+/-0.12, P
      < 0.005, n = 22) with a moderately higher platelet reactivity to collagen. We
      conclude that Ch and Ph were distinctly incorporated to HPPM in the different
      groups of hyperlipidemia and, therefore, that the absolute increase of Ch and Ph
      was more informative to understand the structural and functional modifications of
      the HPPM in hyperlipidemias, than the Ch/Ph molar ratio. On the other hand, the r
      was sensitive to the DPH,35 increase in the content of HPPM Ph and C18:1 + C18:2
      and it was insensitive to the increase in the Ch content.

PMID- 16793722
TI  - Ultrastructural analysis of the distribution of von Willebrand factor and
      fibrinogen in platelet aggregates formed in the PFA-100.
AB  - The PFA-100 is a new apparatus used to detect platelet dysfunction in vitro .
      Anticoagulated blood flows under constant pressure through a capillary, and
      across an aperture that pierces a membrane coated with collagen and either
      epinephrine or ADP. Through their ability to adhere and aggregate, platelets
      occlude the orifice and the closure time is a test of platelet function. Using
      electron microscopy and immunogold staining, we have analyzed the ultrastructure
      of platelet aggregates formed within the aperture and that are responsible for
      the occlusion. Standard electron microscopy showed that the aggregates formed on
      both collagen-epinephrine and collagen-ADP cartridges presented the same
      morphological features. The aggregates were exclusively composed of platelets,
      some of which were degranulated. Degranulation was particularly intense at the
      periphery of the aggregate where platelets were often totally devoid of secretory
      organelles. Immunogold staining on ultrathin frozen sections with polyclonal
      antibodies, allowed us to evaluate the distribution of adhesive proteins such as
      fibrinogen and von Willebrand factor (vWF) within the aggregate. The latter was
      found to be abundant in the intercellular spaces between adjoining platelets.
      Although fibrinogen was also present, its labeling was less intense suggesting
      that vWF is the major protein implicated in the platelet-platelet interactions in
      the aggregates formed in the PFA-100 system. This may be because of the high
      shear rate that occurs across the aperture which suggests that the PFA-100 is
      particularly sensitive for detecting abnormalities of vWF-platelet interactions.

PMID- 16793723
TI  - In contrast to fibrinogen or fibrin, peptide and peptide mimetic binding to
      alphaIIbbeta3 (GPIIb-IIIa) does not cause outside-in signalling as judged by
      measurements of phosphatidylinositol 4,5-bisphosphate.
AB  - Binding of ligands, including RGD-containing peptides, to the platelet fibrinogen
      receptor, integrin alphaIIb beta3 has been reported to cause outside-in signals,
      which result in clustering of occupied receptors and changes in conformation of
      the receptor and its cytoplasmic tails. Thus, the peptides that are usually used
      as inhibitors may function as partial agonists. Binding of ligand, fibrinogen or
      polymerizing fibrin, to platelets with activated alphaIIbbeta3 causes decreases
      in phosphatidylinositol 4,5-bisphosphate (PIP ), which may affect actin
      organization. Whether or not binding to unactivated platelets of the peptide
      RGDS, the fibrinogen gamma -chain C-terminal dodecapeptide (H12), or a high
      affinity RGD mimetic SC-54701B affects phosphoinositide metabolism was tested.
      Although incubation of RGDS (230 microM), dodecapeptide (400 microM) or SC-54701B
      (10 microM) with platelets for 2 min caused trends towards decreases in PIP , no
      significant decreases were found. As a positive control, 2 SC-54701B was shown to
      inhibit the decrease in PIP in ADP-stimulated platelets at concentrations
      consistent 2 with the reported IC50 of 0.12 microM. Thus, binding of peptides or
      the high affinity RGD mimetic does not 50 generate a sufficient signal to affect
      the signalling pathway that is involved phosphoinositide metabolism.

PMID- 16793724
TI  - 'Effects of the angiotensin-converting enzyme inhibitor perindopril on
      endothelial and platelet function in essential hypertension'.

PMID- 16793726
TI  - Chance favors the prepared mind: a tribute to Charles S Carter Jr (1954-2006).

PMID- 16793727
TI  - MSC: a coming of age in regenerative medicine.

PMID- 16793728
TI  - Autoreactive T cells induce in vitro BM mesenchymal stem cell
      transdifferentiation to neural stem cells.
AB  - BACKGROUND: The degree of post-injury inflammation of the damaged area of a
      spinal cord is the main difference between the natural successful repair in
      inferior vertebrates and failure in superior vertebrates. The treatment of rats
      with anti-myelin lymphocytes after experimental spinal cord injury induces their
      functional recovery. On the other hand, mesenchymal stem cells (MSC) from adult
      BM implanted in injured areas recover the morphology and function of spinal cord
      in mammals. The purpose of this study was to determine whether there is a direct
      relationship between anti-nervous tissue T cells and MSC reparatory properties.
      METHODS: Circulating autoreactive lymphocytes of patients with spinal cord
      injuries and amyotrophic lateral sclerosis were isolated and activated in vitro.
      These cells were cocultured with autologous MSC for 2-15 days. Cocultures of non
      selected lymphocytes were used as controls. RESULTS: After 48 h of coculture, MSC
      adopted a spindle shape with polarization of the cytoplasm that resembled bipolar
      neurons. Their nuclei diminished the nucleolus number and the chromatin lost its
      granular appearance. After 15 days of culture the cells developed the typical
      structure of a neural network. No morphologic changes were observed in control
      cultures. The differentiated cells reacted positively to tubuline III, GFAP and
      nestin. No differences were observed between the different patient cell sources.
      DISCUSSION: We observed that autoreactive cells may induce the
      transdifferentiation of MSC to neural stem cells. This T-cell-MSC interaction may
      be a common phenomenon during physiologic nerve tissue repair.

PMID- 16793729
TI  - Combined protocol of cell therapy for chronic spinal cord injury. Report on the
      electrical and functional recovery of two patients.
AB  - BACKGROUND: This is a preliminary report on successful results obtained during
      treatment of two patients with chronic spinal cord injury. The therapeutic
      approach was based on the generation of controlled inflammatory activity at the
      injury site that induced a microenvironment for the subsequent administration of
      autologous, BM-driven transdifferentiated neural stem cells (NSC). METHODS: BM
      mesenchymal stem cells (MSC) were cocultured with the patient's autoimmune T (AT)
      cells to be transdifferentiated into NSC. Forty-eight hours prior to NSC implant,
      patients received an i.v. infusion of 5 x 10(8) to 1 x 10(9) AT cells. NSC were
      infused via a feeding artery of the lesion site. Safety evaluations were
      performed everyday, from the day of the first infusion until 96 h after the
      second infusion. After treatment, patients started a Vojta and Bobath
      neurorehabilitation program. RESULTS: At present two patients have been treated.
      Patient 1 was a 19-year-old man who presented paraplegia at the eight thoracic
      vertebra (T8) with his sensitive level corresponding to his sixth thoracic
      metamere (T6). He received two AT-NSC treatments and neurorehabilitation for 6
      months. At present his motor level corresponds to his first sacral metamere (S1)
      and his sensitive level to the fourth sacral metamere (S4). Patient 2 was a 21
      year-old woman who had a lesion that extended from her third to her fifth
      cervical vertebrae (C3-C5). Prior to her first therapeutic cycle she had severe
      quadriplegia and her sensitive level corresponded to her second cervical metamere
      (C2). After 3 months of treatment her motor and sensitive levels reached her
      first and second thoracic metameres (T1-T2). No adverse events were detected in
      either patient. DISCUSSION: The preliminary results lead us to think that this
      minimally invasive approach, which has minor adverse events, is effective for the
      repair of chronic spinal cord lesions.

PMID- 16793730
TI  - Implantation of BM mesenchymal stem cells into injured spinal cord elicits de
      novo neurogenesis and functional recovery: evidence from a study in rhesus
      monkeys.
AB  - BACKGROUND: Transplantation of mesenchymal stem cells (MSC) in rodent models has
      proved to be an effective therapeutic approach for spinal cord injury (SCI).
      However, further studies in primate models are still needed before clinical
      application of MSC to patients. METHODS: MSC were isolated from rhesus monkey BM
      and induced ex vivo to differentiate into neural lineage cells. Induced cells
      were labeled with Hoechst 33342 and injected into the injured sites of rhesus SCI
      models. Function of the injured spinal cord was assessed using Tarlov behavior
      assessment, sensory responses and electrophysiologic tests of cortical
      somatosensory-evoked potential (CSEP) and motor-evoked potential (MEP). In vivo
      differentiation of the implanted cells was demonstrated by the presence of neural
      cell markers in Hoechst 33342-labeled cells. The re-establishment of the axonal
      pathway was demonstrated using a true blue (TB) chloride retrograde tracing
      study. RESULTS: Monkeys achieved Tarlov grades 2-3 and nearly normal sensory
      responses 3 months after cell transplantation. Both CSEP and MEP showed recovery
      features. The presence of the neural cell markers neurofilament (NF), neuro
      specific enolase (NSE) and glial fibrillary acidic protein (GFAP) was observed in
      approximately 10% of Hoechst 33342-labeled cells. TB, originally injected at the
      caudal side of injured sites, was traceable in the rostral thoracic spinal cord,
      red nucleus and sensory motor cortex. DISCUSSION: Our results suggest that the
      implantation of MSC-derived cells elicits de novo neurogenesis and functional
      recovery in a non-human primate SCI model and should harness the clinical
      application of BM MSC in SCI patients.

PMID- 16793731
TI  - In vitro endothelial potential of human UC blood-derived mesenchymal stem cells.
AB  - BACKGROUND: Human mesenchymal stem cells (MSC) possess powerful ex vivo expansion
      and versatile differentiation potential, placing themselves at the forefront of
      the field of stem cell-based therapy and transplantation. Of high clinical
      relevance is the endothelial differentiation potential of MSC, which can be used
      to treat various forms of ischemic vascular disease. METHODS: We investigated
      whether human umbilical cord blood (UCB)-derived MSC are able to differentiate in
      vitro along an endothelial lineage, by using flow cytometry, RT-PCR and
      immunofluorescence analyzes, as well as an Ab array method. RESULTS: When the
      cells were incubated for up to 3 weeks in the presence of VEGF, EGF and
      hydrocortisone, they began to express a variety of endothelial lineage surface
      markers, such as Flk-1, Flt-1, VE-Cadherin, vWF, VCAM-1, Tie-1 and Tie-2, and to
      secrete a specific set of cytokines. Differentiated cells were also found to be
      able to uptake low-density lipoprotein and form a tubular network structure.
      DISCUSSION: These observations have led us to conclude that UCB-derived MSC
      retain endothelial potential that is suitable for basic and clinical studies
      aimed at the development of vasculature-directed regenerative medicine.

PMID- 16793732
TI  - Undifferentiated mouse mesenchymal stem cells spontaneously express neural and
      stem cell markers Oct-4 and Rex-1.
AB  - BACKGROUND: Previous adult stem cells studies have provided evidence that BM
      mesenchymal stem cells (MSC) exhibit multilineage differentiation capacity. These
      properties of MSC prompted us to explore the neural potential of MSC with a view
      to their use for the treatment of demyelinating disorders, such as multiple
      sclerosis. Indeed, issues such as the identification of a subset of stem cells
      that is neurally fated, methods of expansion and optimal stage of differentiation
      for transplantation remain poorly understood. METHODS: In order to isolate mouse
      (m) MSC from BM, we used and compared the classic plastic-adhesion method and one
      depleting technique, the magnetic-activated cell sorting technique. RESULTS: We
      established and optimized culture conditions so that mMSC could be expanded for
      more than 360 days and 50 passages. We also demonstrated that undifferentiated
      mMSC express the neural markers nestin, MAP2, A2B5, GFAP, MBP, CNPase, GalC, O1
      under standard culture conditions before transplantation. The pluripotent stem
      cell marker Oct-4 and the embryonic stem cell marker Rex-1 are spontaneously
      expressed by untreated mMSC. The lineage-negative mMSC (CD5- CD11b- Ly-6G- Ter119
      CD45R- c-kit/CD117-) overexpressed Oct-4, O1 and A2B5 in the first days of
      culture compared with the non-sorted MSC. Finally, we identified a distinct
      subpopulation of mMSC that is primed towards a neural fate, namely Sca-1+/nestin+
      mMSC. DISCUSSION: These results should facilitate the optimal timing of
      harvesting a neurally fated subpopulation of mMSC for transplantation into animal
      models of human brain diseases.

PMID- 16793733
TI  - Use of CFDA-SE for evaluating the in vitro proliferation pattern of human
      mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSC) are multipotent progenitors retaining
      the capability to undergo multilineage differentiation, mostly towards all the
      mesodermal cellular lineages. MSC growing under standard conditions are composed
      of two main subpopulations with a characteristic distribution in the morphologic
      flow cytometric scatter: RS (recycling stem) cells (small, agranular) and m
      (mature) MSC (large, moderately granular cells). METHODS: MSC obtained from BM of
      healthy donors and expanded in culture were characterized by evaluating both the
      expression of conventional markers and differentiation potential. We used CFSE, a
      lipophilic dye that is taken up by cell membranes, to investigate separately the
      proliferative activity of RS cells and mMSC subsets. RESULTS: With flow
      cytometric analysis, RS cells and mMSC showed nearly the same immunophenotypic
      pattern, even if a significantly smaller percentage of RS cells expressed some of
      the classic mesenchymal Ag. The RS cell fraction was confirmed to have a higher
      proliferative potential and such a feature was particularly evident under certain
      culture conditions. DISCUSSION: CFSE has been shown as a reliable method for
      studying the proliferative activity of MSC subpopulations identified by flow
      cytometric analysis. The acquisition parameter strategy is crucial for the
      accuracy of the analysis.

PMID- 16793734
TI  - Multi-laboratory evaluation of procedures for reducing the volume of cord blood:
      influence on cell recoveries.
AB  - BACKGROUND: Various procedures can be used to isolate stem and progenitor cells
      from cord blood. This study evaluated the hydroxyethyl starch sedimentation (HES)
      with two centrifugation steps, and the top and bottom (T&B) isolation of buffy
      coat following a single centrifugation, and two filter systems for processing
      cord blood, one developed by Asahi Kasei Medical (filter A) and the second by
      Terumo (filter B). METHODS: Each of seven laboratories was randomly assigned the
      evaluation of either the HES or T&B method and one of the filter methods (n=8
      cord blood units, per laboratory, for each method). The leukocyte-containing
      fraction with the stem/progenitor cells was recovered from the filters by reverse
      flushing. Utilizing the routine traditional processing and testing procedures of
      each laboratory, in vitro parameters were determined, with samples obtained after
      collection, after processing and after freezing/thawing. The results were
      expressed as the percentage recovery of viable cells in processed vs. collected
      samples (performance 1; PF1) and in thawed vs. processed samples (performance 2;
      PF2). The composite results obtained by the seven laboratories were summarized.
      RESULTS: The median PF1 percentage recovery of total nucleated cells (TNC) was
      comparable with both traditional methods (HES 79%, T&B 86%) and statistically
      reduced with both filtration procedures (filter A 58%, filter B 61%). Mononuclear
      cell (MNC) PF1 recovery was highest statistically with the T&B method (91%) and
      reduced on using filter A (77%) and filter B (70%) and the HES method (72%).
      CD34+ cell recovery was judged to be essentially comparable with the four
      methods, although the range of unit recoveries differed. The percentage recovery
      of TNC and MNC in PF1 was influenced by the volume of the collected cord blood,
      especially with use of the filtration procedures. This correlated with TNC
      content. A greater percentage of red cells and platelets was removed during
      processing with both filter methods. The time to process cord blood preparations
      with filter A was significantly shorter than the other methods. Processing with
      the HES method took the longest time. The recoveries for TNC, MNC and CD34+ cells
      in PF2 did not appear to be influenced by the specific processing procedure.
      DISCUSSION: These data indicate that filters that capture stem and progenitor
      cells may be an appropriate methodology for processing cord blood collected for
      banking.

PMID- 16793735
TI  - Analysis and cryopreservation of hematopoietic stem and progenitor cells from
      umbilical cord blood.
AB  - BACKGROUND: Umbilical cord blood (UCB) is an important source of hematopoietic
      stem and progenitor cells (HSC/HPC) for the reconstitution of the hematopoietic
      system after clinical transplantation. Cryopreservation of these cells is
      critical for UCB banking and transplantation as well as for research applications
      by providing readily available specimens. The objective of this study was to
      optimize cryopreservation conditions for CD34+ HSC/HPC from UCB. METHODS:
      Cryopreservation of CD34+ HSC/HPC from UCB after mononuclear cell (MNC)
      preparation was tested in a research-scale setup. Experimental variations were
      concentration of the cryoprotectant, the protein additive and cell concentration.
      In addition, protocols involving slow, serial addition and removal of DMSO were
      compared with standard protocols (fast addition and removal of DMSO) in order to
      avoid osmotic stress for the cryopreserved cells. Viability and recoveries of
      MNC, CD34+ cells and total colony-forming units (CFU) were calculated as read
      outs. In addition, sterility testing of the collected UCB units before further
      processing was performed. RESULTS: The optimal conditions for cryopreservation of
      CD34+ HPC in MNC preparations were 10% DMSO and 2% human albumin at high cell
      concentrations (5 x 10(7) MNC/mL) with fast addition and removal of DMSO. After
      cryopreservation using a computer-controlled freezer, high viabilities (89%) and
      recoveries for CD34+ cells (89%) as well as for CFU (88%) were observed.
      Microbial contamination of the collected UCB samples was reduced to a rate of
      6.4%. DISCUSSION: Optimized cryopreservation conditions were developed for UCB
      MNC in respect of the composition of the cryosolution. In addition, our results
      showed that fast addition of DMSO is essential for improved cryopreservation and
      post-thaw quality assessment results, whereas the speed of DMSO removal after
      thawing has little influence on the recoveries of CD34+ cells and CFU.

PMID- 16793736
TI  - Production of myeloid dendritic cells (DC) pulsed with tumor-specific idiotype
      protein for vaccination of patients with multiple myeloma.
AB  - BACKGROUND: Immunotherapy of cancer with DC vaccines has produced encouraging
      results in clinical trials. Antigen (Ag)-pulsed DC have elicited CD4+ and CD8+ T
      cell immunity and tumor regression in humans. However, there is no standard
      method of DC production. The DC phenotype, number and Ag-loading process used in
      these studies have varied, making comparisons between trials difficult. METHODS:
      In the present report a reproducible method was developed for the production of a
      DC-based vaccine. Monocytes were enriched by adhesion from healthy donor
      apheresis products and cultured with growth factors for maturation into DC. The
      cells were loaded with the tumor Ag idiotype proteins from patients with multiple
      myeloma. DC culture and Ag loading were performed in an automated and closed
      system. The DC product was characterized for phenotype by flow cytometry and for
      function in Ag uptake and Ag presentation. RESULTS: These monocyte-derived DC
      expressed high levels of costimulatory molecules (CD80/86). Ag-pulsed DC
      functioned to induce allogeneic proliferative lymphocyte responses and Ag
      specific cytotoxic T lymphocyte (CTL) responses. The DC viability, phenotype and
      function were well preserved following prolonged frozen storage. Aliquots from
      the product of a single DC preparation could be used for sequential vaccinations
      without batch to batch variability. DISCUSSION: Ag-pulsed DC can be reproducibly
      generated for clinical use. These standardized methods are now being employed for
      a clinical trial to evaluate idiotype-pulsed DC vaccine therapy following non
      myeloablative transplant for the treatment of multiple myeloma.

PMID- 16793737
TI  - Testing the safety of clinical-grade mature autologous myeloid DC in a phase I
      clinical immunotherapy trial of CML.
AB  - BACKGROUND: We conducted a phase I clinical immunotherapy trial of CML to
      evaluate the safety of a clinical-grade leukemic DC product standardized for
      purity and mature phenotype. METHODS: We injected autologous DC into patients in
      late chronic or accelerated phases of CML. The patients received mature CD83+ and
      bcr-abl+ DC prepared from CD14+ cells. Two cohorts of three patients received
      four injections each of 3 x 10(6) DC and 15 x 10(6) DC/injection, respectively.
      The first patient was studied before imatinib mesylate (IM) was available, four
      patients were treated concurrently with IM therapy and one did not tolerate the
      IM and was off the drug at the time of DC therapy. IM effects on WBC counts
      precluded DC preparation in numbers sufficient for further dose escalation. The
      first patient received DC s.c. and all subsequent patients received DC into a
      cervical lymph node under ultrasound guidance. RESULTS: DC injections were well
      tolerated. We observed no clinical responses. T cells drawn later in the course
      of therapy were more sensitive to stimulation by CML DC in vitro. DISCUSSION: The
      increase in T-cell sensitivity to CML-specific stimulation that accompanied
      active immunization by CML DC justifies further clinical studies, possibly with
      modifications such as an increased frequency and number of DC injections.

PMID- 16793738
TI  - Growth kinetics of progenitor cell-enriched hematopoietic cell populations in
      long-term liquid cultures under continuous removal of mature cells.
AB  - BACKGROUND: During long-term culture of primitive hematopoietic cells large
      numbers of mature cells are generated that, on the one hand, consume nutrients
      and cytokines present in the medium and, on the other hand, may produce or elicit
      the production of soluble factors that limit the growth of primitive cells. Thus
      it is possible that under standard culture conditions hematopoietic stem and
      progenitor cells are unable to display their true proliferation and expansion
      potentials. METHODS: Hematopoietic cell populations, enriched for CD34+ cells,
      were obtained from both umbilical cord blood (UCB) and mobilized peripheral blood
      (MPB), and cultured in cytokine-supplemented liquid culture, under continuous
      removal of mature cells by means of weekly re-selection of primitive, lineage
      negative (Lin-) cells. Proliferation and expansion capacities of such cells were
      determined weekly for a 42-day culture period. RESULTS: As expected, based on our
      previous studies in standard liquid cultures, throughout the culture period there
      was a continuous decrease in the proportion of progenitor cells; however, after
      every re-selection on days 7, 14 and 21, there was a significant enrichment for
      both CD34+ cells and colony-forming cells (CFC). As a result of such an
      enrichment, the cumulative increase in the numbers of total cells and CFC in
      cultures with two, three or four selections was significantly higher than the
      increments observed in standard cultures, in which only a single selection was
      performed on day 0. Cultures of UCB cells showed consistently higher levels of
      both total cells and CFC than cultures of MPB cells. DISCUSSION: Taken together,
      these results indicate that continuous removal of mature cells from liquid
      cultures of primitive progenitors results in higher increments in the levels of
      both total cells and CFC.

PMID- 16793740
TI  - The molecular genetics of Glanzmann's thrombasthenia.

PMID- 16793739
TI  - Autologous transplantation of CD133+ BM-derived stem cells as a therapeutic
      option for dilatative cardiomyopathy.
AB  - We report the case of a 58-year-old man with end-stage non-ischemic
      cardiomyopathy. Baseline transthoracic echocardiography (TTE) and cardiac
      magnetic resonance (cMRI) revealed a markedly depressed left ventricle systolic
      function. He underwent autologous CD133+ BM-derived cell transplantation through
      a minimally invasive approach. During surgery 19 x 10(6) BM-derived stem cells
      were injected by the transepimyocardial route. Six months after the operation TTE
      and cMRI showed a clear improvement in left ventricular contractility.

PMID- 16793741
TI  - Molecular genetics of the Hermansky-Pudlak and Chediak-Higashi syndromes.
AB  - Hermansky-Pudlak syndrome(HPS) and Chediak-Higashi syndrome(CHS) are similar but
      distinct autosomal recessive genetic diseases in which a bleeding diathesis
      resulting from platelet storage pool deficiency is accompanied by deficient
      pigmentation of the skin and hair and various systemic abnormalities associated
      with defective lysosomal function. The diverse multi-systemic manifestations of
      HPS and CHS are associated with abnormalities of a number of different
      cytoplasmic organelles--platelet dense granules, melanosomes, lysosomes and
      various cytoplasmic secretory granules. Though rare, HPS and CHS probably
      represent just the first of what will eventually be a novel class of genetic
      disorders resulting from defective biogenesis, structure or function of these
      organelles. The genes responsible for HPS and CHS have recently been identified
      and are beginning to yield insights into the molecular genetics and cellular
      pathophysiology of these intriguing disorders.

PMID- 16793742
TI  - Modulation of hematopoiesis by ketanserin in erythropoietin-treated uremic
      patients: evidence from platelet studies.
AB  - Recombinant human erythropoietin (EPO) not only ameliorates the anemia of renal
      failure but also modulates platelet function and corrects uremic platelet
      serotonin (5-hydroxytryptamine, 5-HT) storage pool deficiency. We studied if
      ketanserin, a blocker of platelet and vascular smooth muscle receptors for 5-HT,
      could reverse any EPO-induced changes in hemostasis. A complete blood count,
      immunoreactive serum EPO concentration, skin bleeding time (BT) and whole blood
      platelet aggregation (electric impedance method) induced by ristocetin and ADP,
      and intraplatelet and whole blood 5-HT, were determined in seven chronic
      hemodialysis (HD) patients before and after 1, 2, 4 and 8 weeks of EPO therapy,
      and repeated after a 4-week co-treatment with oral ketanserin. Stimulation of
      erythropoiesis was accompanied by a rise in the platelet count ( P < 0.05),
      shortening of the BT ( P < 0.02), an increase in platelet aggregability, and by
      replenished intraplatelet 5-HT store. Ketanserin co-treatment produced an
      unexpected 33% fall in serum EPO level ( P < 0.02), a decrease in the platelet
      count ( P < 0.05), prolongation of the BT ( P < 0.05) and depressed platelet
      aggregation in response to both agonists. There was no change in the amount of
      intraplatelet 5-HT while whole blood 5-HT concentration decreased significantly (
      P < 0.02). Strong positive correlations between the decrease in whole blood 5-HT
      and the prolongation of the BT ( r = 0.786, P < 0.05), and between the former
      parameter and the fall in the platelet count ( r = 0.820, P < 0.05) were found.
      In conclusion, we report dual erythro- and thrombocytopoietic effects of EPO
      combined with correction of a platelet defect in the storage of 5-HT and enhanced
      platelet aggregability. The ketanserin-induced falls in serum EPO concentration
      and the platelet count provide new evidence of the dependency of
      thrombocytopoiesis on EPO in the initial weeks of the therapy. The 'antiplatelet'
      effects of ketanserin observed in this study seem to be due to reduction in
      circulating thrombocyte number rather than from any inhibitory effect on their
      aggregation.

PMID- 16793743
TI  - RNA-mediated regulation of Bc1-2 and cyclin 'D' genes in human platelets.
AB  - The aim of this study was to understand the RNA-mediated regulation of genes
      coding for Bc1-2 and cyclin 'D'. Evidence was provided that these genes are
      regulated by receptor-C(k)-dependent signalling in human platelets. Further
      experiments to resolve the mechanism through which receptor-C(k) regulates these
      genes revealed that receptor-C(k)-dependent signalling is involved in the
      cleavage of a 125-kDa protein present in endoplasmic reticulum, resulting in
      generation of a 47-kDa factor that has affinity for a genomic sterol regulatory
      element as well as the platelet mRNA pool. Based upon these findings we propose a
      receptor-C(k) dependent signalling pathway for the regulation of Bc1-2 and cyclin
      'D' genes at the post-transcriptional level.

PMID- 16793744
TI  - Lorenzo's oil and platelet activation in adrenomyeloneuropathy and asymptomatic X
      linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal
      beta-oxidation, which results in accumulation of very long-chain fatty acids,
      causing damage to the nervous system, adrenal cortex and testis. The two most
      frequent phenotypes are childhood cerebral adrenoleukodystrophy (CCALD) and
      adrenomyeloneuropathy (AMN). Some affected males demonstrate no clinical signs
      (asymptomatic ALD), whereas female carriers can also be affected. Patients with X
      ALD have been treated with Lorenzo's oil, a 4:1 combination of oleic acid and
      erucic acid, with thrombocytopenia as the main side effect and sometimes leading
      to a hemorrhagic diathesis. We studied platelet count, size and membrane surface
      exposure of platelet activation antigens in 17 adult X-ALD patients. Eight
      patients used the prescribed amount of erucic acid (as glyceroltrierucate) or
      more (very compliant), five used less(compliant), and four did not use the diet.
      All eight very compliant patients had highly enlarged platelets and seven
      manifested thrombocytopenia. An enhanced in vivo platelet activation status was
      established by increased platelet surface expression of P-selectin (CD62P,
      PADGEM, GMP-140) in five of the seven thrombocytopenic patients, and of increased
      fibrinogen receptor exposure (measured with the antibody PAC-1) in three of these
      five patients. The other nine compliant or untreated patients had normal platelet
      counts and, generally, normal P-selection and fibrinogen receptor expression. A
      diet-induced 7- to 27-fold enrichment of erucic acid was observed in the
      platelets of the four patients studied. We conclude that the thrombocytopenia in
      AMN patients using Lorenzo'soil is associated with circulating platelets that
      have an increased erucic acid content, size and activation status. We hypothesize
      that the erucic acid in some way induces the increased size and thus, directly or
      indirectly, increased platelet activation or instability in vivo. This then
      causes the thrombocytopenia, with circulating platelets representing a population
      that has not yet been sufficiently changed to be removed, but has clear signs of
      activation.

PMID- 16793745
TI  - Effects of clopidogrel and its inactive form, SR 25989, on plasma, liver and
      platelet lipids in the rat.
AB  - The aim of the present study was to determine whether clopidogrel, one of the
      most potent antiplatelet compounds in vivo, could alter the lipid composition of
      plasma, liver tissue or platelet membranes in the rat. Animals treated (10 mg/kg
      per day for 7 days) with clopidogrel and its inactive analogue (R form, SR 25989)
      were compared with control animals. Neither compound altered plasma
      concentrations of triglycerides or free and esterified cholesterol, and no
      changes were observed in liver lipids. Clopidogrel treatment significantly
      lowered platelet cholesterol content and cholesterol to phospholipid ratio, while
      SR 25989 had comparatively smaller effects. Concerning platelet phospholipids,
      clopidogrel treatment reduced phosphatidylcholine(PC) but increased sphingomyelin
      (SP) content, whereas SR 25989 lowered PC and phosphatidylserine (PS) but raised
      phosphatidylethanolamine (PE) content. A significant increase in the arachidonic
      acid content of PE was observed only in the SR 25989 group. Clopidogrel and SR
      25989 both induced an increase in the unsaturation level of platelet PC,
      accompanied by a decrease in the level of unsaturation in platelet SP, while a
      similar decrease was observed for phosphatidylinositol only in the clopidogrel
      group. These changes in platelet membrane composition in the clopidogrel group
      are probably unrelated to the antiaggregating properties of the drug, but could
      influence other platelet functions under long-term treatment.

PMID- 16793746
TI  - Identification of arrestin-like proteins in a human megakaryocytic cell line (HEL
      cells).
AB  - Proteins of the arrestin family contribute to the regulation of G-protein
      mediated signal transduction in a number of tissues, possibly by a
      desensitization of the appropriate receptor(s). In this study we demonstrate the
      presence of arrestin-related proteins in a megakaryoblast-like cell line (HEL).
      Mouse monoclonal and rabbit polyclonal antibodies were prepared against visual
      arrestin, against a synthetic peptide'GFLGELTSSEVATEVPFRLM' (a pathogenic
      sequence corresponding to residues 340 to 359 of human visual arrestin), and
      against the peptide 'VDTNLIEFDTNDDDIV' that represents an aminoacid sequence
      present in beta -arrestins 1 and 2 but absent from visual arrestin. In Western
      blots, all of these antibodies revealed a 48-kDa protein in HEL cell extract.
      Using a beta-arrestin specific primer, RT-PCR of RNA from HEL cells confirmed the
      presence of beta-arrestin mRNA, with a predicted 480 bp having 98.8% homology
      with beta-arrestin. These results suggest that arrestin-family proteins may be
      involved in the desensitization of G-protein mediated receptors in platelets.

PMID- 16793747
TI  - Effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril on
      endothelial and platelet functions in essential hypertension.
AB  - Endothelial damage and platelet hyperactivity may play a role in the vascular
      complications of essential hypertension. Restoration of endothelial function and
      reduction of increased platelet aggregation in essential hypertension are one of
      the aims of modern anti-hypertensive therapy. Therefore, the effect of
      angiotensin converting enzyme (ACE) inhibitors on endothelial and platelet
      functions is of interest. In the present study, 23 healthy normotensives and 23
      age- and sex-matched patients with non-treated essential hypertension (1st and
      2nd stage according to WHO) were investigated. Measurements of endothelial and
      platelet functions in hypertensives were carried out before therapy, after 1 week
      of placebo administration, after 1 week and after 1 month of perindopril therapy
      in a once daily dose of 4 mg. Plasma thrombomodulin (ELISA method) and beta
      thromboglobulin (radio immunoassay method) were assayed and platelet aggregation
      (spontaneous and induced by adrenaline) was measured. The values of plasma
      thrombomodulin, a novel marker of endothelial function, were compared between age
      and sex-matched normotensives and hypertensives. A significant decrease of
      adrenaline-induced platelet aggregation was observed after 1 month of perindopril
      therapy in comparison with the values before therapy or after 1 week of
      perindopril therapy ( P < 0.02 and P < 0.05 respectively). There were no
      significant changes in plasma thrombomodulin or beta-thromboglobulin following
      therapy. We failed to find significant changes of plasma thrombomodulin in
      patients in the early stages of hypertension, but its tendency to be higher than
      in normotensives does not rule out some vascular damage. The inhibitory effect of
      perindopril on platelet aggregation may be a further advantage of this drug.
      Since no changes were found after 1 week of therapy, the reduction of adrenaline
      induced platelet aggregation after 1 month of therapy may be explained by an
      indirect effect of perindopril on platelet function, probably asa result of
      protective action on the arterial wall.

PMID- 16793749
TI  - Is clopidogrel markedly superior to aspirin in patients with peripheral vascular
      disease?

PMID- 16793748
TI  - Inhibitory effects of cisplatin and its conjugate with glutathione on blood
      platelet activity.
AB  - Cisplatin (cis -diamminedichloroplatinum II, CDDP) is a widely used
      chemotherapeutic agent; however, its haematological toxicity may become an
      important dose-limiting factor. The aim of the present study was to evaluate the
      effects of cisplatin and its metabolite with glutathione (GS-Pt conjugate) on
      thrombin-induced platelet aggregation, the secretory process and the arachidonate
      pathway in vitro. Pre-treatment of platelets with GS-Pt conjugate (60 min, 20
      microM) but not with cisplatin alone, caused inhibition of thrombin-induced
      platelet aggregation. GS-Pt conjugate had also a strong inhibitory effect on the
      release of proteins and adenine nucleotides from platelet granules. After pre
      incubation of platelets with cisplatin and its conjugate, we observed in thrombin
      activated platelets, a decreased amount of malonyldialdehyde (a marker of
      thromboxane A(2) synthesis). We suggest that arachidonate metabolism plays an
      important role in determining the cytotoxicity of cisplatin.

PMID- 16793751
TI  - Elevated thrombopoietin serum concentrations in myelodysplasias.
AB  - Thrombopoietin (TPO) serum levels were quantified in patients with
      myelodysplastic syndromes using an ELISA test for TPO. We found that TPO levels
      were significantly elevated in the whole group of patients as compared with
      normal healthy donors (521.9 75.3 pg/ml vs 160.1 19.6 pg/ml; P = 0.011). TPO
      serum levels were inversely correlated with the megakaryocyte mass in both the
      RA/RARS and RAEB/RAEBt subgroups ( P = 0.012 and P = 0.031, respectively). Two
      subsets of patients with a possible dysregulation of TPO production were
      identified.

PMID- 16793752
TI  - Expression of GTP-binding proteins and protein kinase C isozymes in platelet-like
      particles derived from megakaryoblastic leukemia cells (MEG-01).
AB  - The expression of the various GTP-binding proteins and protein kinase C (PKC) in
      the platelet-like particles produced by MEG-01 cells was analyzed by RT-PCR and
      immunoblotting. We selected 14 human low Mr GTPbinding proteins (LMW-GPs) and
      nine PKCs expressed in platelets and/or megakaryocytes, and designed specific
      primer pairs for the proteins. RT-PCR analysis revealed that the particles
      express the mRNAs of many LMW-GPs such as rap 1A, rap 1B, rap 2B, ral A, rho A,
      rac 1, rac 2, Cdc 42, rab 1, rab 3B, rab 6, ram/rab 27 and ran . By
      immunoblotting analysis, Rap1, RhoA, Rac, Cdc42, Rab6 and Rab8 were identified in
      the particles. As for PKCs, the particles were observed to express the mRNAs of
      PKC-alpha,-beta I, -beta-II, -delta, epsilon, eta and theta, but not-gamma and
      zeta. Using immunoblot analysis, PKC-beta I, -beta II and zeta were shown to
      exist in the particles, although the contents were lower than those in platelets.
      Furthermore, the presence of Gi2-alpha, a heterotrimeric G protein that is the
      major pertussis toxin substrate in human platelets, and beta subunits was
      observed in the particles. Taken together, the particles possess some similarity
      to human platelets based on the expression profiles of GTP-binding proteins and
      PKCs.

PMID- 16793750
TI  - Frozen extracellular matrix preserves its thrombogenicity after thawing, while
      Matrigel induces a poor platelet response.
AB  - Two putative substitutes for fresh endothelial cell (EC) extracellular matrix
      (ECM), frozen ECM and Matrigel, were studied using a parallel-plate perfusion
      system and platelet deposition was evaluated morphometrically. Coverslips covered
      with ECM were stored frozen at-30 C for 0 (fresh ECM), 1, 2, 3 or 4 weeks. The
      ability of frozen ECM to support platelet adhesion after freezing was analyzed
      under three experimental approaches, perfusing blood: (i) at different shear
      rates; (ii) on a highly reactive ECM obtained from stimulated EC; and (iii) on
      ECM incubated with a monoclonal antibody against laminin (LM). Matrigel, alone or
      mixed with different fractions of wet cryoprecipitate, was layered on coverslips
      as a thin uniform coat, and perfused, as was done with the frozen ECM. Platelet
      deposition onto fresh ECM was 21.3 1.5%, 25.5 2.1% and 30.8 2.4% (at shear rates
      of 300, 800 and 1300/s, respectively) and 40.0 3.8% in PMA stimulated ECM
      perfused at 800/s. Values obtained on frozen ECM did not vary from those obtained
      using fresh ECM. Results from perfusion studies using ECM preincubated with an
      anti-laminin antibody and observations from immunofluorescence studies indicated
      that the presence and distribution of the adhesive proteins in frozen ECM were
      similar to those observed on fresh ECM. Platelet deposition on Matrigel was
      practically absent. Addition of a 20% cryoprecipitate fraction partially restored
      its thrombogenicity. Our results indicate that when ECM is kept frozen for up to
      4 weeks, it behaves as fresh ECM in perfusion studies. On the contrary, Matrigel
      is not a suitable substrate to support platelet attachment under flow conditions.

PMID- 16793753
TI  - 12(S)-HETE plays a role as a mediator of expression of platelet CD62 (P
      selectin).
AB  - The role of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE), an
      abundant lipoxygenase product from arachidonic acid in platelets, remains
      unknown. We investigated and characterized the role of 12(S)-HETE in platelet
      activation. 12(S)-HETE production and CD62 expression were increased by
      stimulation with thrombin at 0.03 U/ml or higher, while TXB2 synthesis was
      increased by thrombin at 0.1 U/ml or higher. The platelet 12(S)-HETE production
      was increased 10 s after stimulation and this was earlier than CD62 expression.
      The expression of CD62 was inhibited by the lipoxygenase (LOX) inhibitors
      quercetin and nordihydroguaiaretic acid but was not affected by the
      cyclooxygenase (COX) inhibitors aspirin and indomethacin. Exogenously added 12(S)
      HPETE and 12(S)-HETE enhanced CD62 expression, but other HETEs did not.
      Consequently, 12-LOX products play a role in the expression of CD62 and could be
      a second messenger for platelet activation.

PMID- 16793754
TI  - A monoclonal antibody raised against pig leukocytes and platelets recognizes
      fibrinogen from pig plasma.
AB  - Monoclonal antibody (mab) JM7E6 was produced through immunization of mice with
      porcine peripheral blood mononuclear cells and platelets. Biochemical
      characterization of the antigen showed three bands of 48, 55 and 60 kDa
      approximately, under reducing condition, and a single band greater than 200 kDa,
      under non-reducing condition. The antigen distribution among leukocyte
      subpopulations was reduced, but abundant in platelets, which suggests the
      recognition of a platelet antigen. However, immunohistochemical analysis of
      paraffin-embedded porcine tissues showed reactivity on blood vessel plasma, and
      indicates recognition of a plasma protein. ELISA and immunoblotting techniques,
      which were performed with commercially available porcine fibrinogen, not only
      confirmed the identification of this antigen, but also localized the epitope
      recognized by JM7E6 in the fibrinogen gamma light chain. JM7E6 failed to
      recognize human, ovine, bovine and dog fibrinogen molecules, thus showing species
      specificity of the epitope recognized by this antibody. Since JM7E6 is able to
      precipitate fibrinogen molecules from porcine leukocytes and platelets, it may be
      a valuable tool for some interesting clinical applications.

PMID- 16793755
TI  - Effects on platelet function of combination etoposide and carboplatin
      chemotherapy in pediatric oncology patients.
AB  - The effects of a therapeutic course of the combination of carboplatin and
      etoposide on platelet function have been evaluated in 10 pediatric patients with
      brain tumors. Platelet count, in vitro aggregation tests, P-selectin expression
      and agonist-induced ATP release were evaluated before, and 7 and 15 days after
      one cycle of chemotherapy. The analysis of the results demonstrated the presence
      of an in vitro platelet aggregation defect in response to collagen and
      arachidonic acid in all patients 7 days after therapy. A concomitant decrease of
      collagen- and arachidonic acid-induced ATP release was also observed. Both
      platelet aggregation and ATP release returned to baseline values 15 days after
      chemotherapy administration. Conversely, in vitro platelet aggregation and
      secretion induced by ADP and epinephrine were unaltered by carboplatin and
      etoposide administration. Furthermore, P-selectin expression was negative at
      baseline and did not change after chemotherapy. These results support the
      hypothesis that combination etoposide and carboplatin chemotherapy in pediatric
      patients is responsible for possible disturbances in biochemical pathways
      required for platelet secretion and aggregation.

PMID- 16793756
TI  - Membrane lipid fluidity of blood platelets: a common denominator that underlies
      the opposing actions of various agents that affect platelet activation in whole
      blood.
AB  - Membrane lipid fluidity (MLF) is thought to play a crucial role in signal
      transduction and is believed to affect the responsiveness of blood platelets. In
      a recent study it was demonstrated that EDTA, used as the blood anticoagulant,
      brought about a significant increase in expression of GMP-140 antigen, and this
      effect was accompanied by a significant increase in platelet MLF. Moreover, this
      spontaneous EDTA-driven platelet activation was vastly attenuated in the presence
      of tissue-type plasminogen activator, which is also known to affect platelet MLF.
      The hypothesis was raised that the modulation of platelet membrane fluidity by
      EDTA might underlie platelet spontaneous activation in the presence of EDTA. To
      further explore the possible molecular mechanism(s) of the EDTA-dependent
      triggering of signal transduction pathway(s) in human blood platelets, we
      monitored the extent of spontaneous platelet activation in the presence of EDTA
      and selected platelet membrane 'fluidizers' and 'rigidizers'. A reduction in the
      EDTA-dependent platelet release and activation was noted, not only in the
      presence of rt-PA (by over 50%, P < 0.001), which acted as a rigidizer of
      platelet membrane fluidity (ESR h+1/h0 ratios of 5-DOXYL-Ste and 12-DOXYL-Ste
      decreased by 6.2%, P<< 0.0001, and 3.8%, P < 0.02, respectively), but also in the
      presence of other modulators of MLF, regardless of their fluidizing or rigidizing
      effects. Both rigidizers (procaine and lidocaine, 5-DOXYL-Ste h+1/h0 reduced by
      up to 6.5%, 12-DOXYL-Ste h+1/h0- by up to 4.5%, P < 0.02 or less) and fluidizers
      (benzyl alcohol, ethanol, 12-DOXYL-Ste h+1/h0 increased by 17.8% and 6.1%,
      respectively, P <<0.0001) of platelet membranes significantly depressed platelet
      activation (respectively, down to 1.1%, 7.7%, 6.7% and 8.5% vs control EDTA 22.9%
      of CD62-positive platelets). We suggest that EDTA induces alterations in membrane
      glycoprotein structure and affect MLF by altering lipid-protein interactions, and
      thus triggers signal transduction in the course of platelet activation. The
      resulting displacements in platelet membrane proteins, dislocation of membrane
      components and/or distortion of lipid-protein interactions could generate an
      'outside-in' signalling that is mediated by the altered platelet MLF. Overall, it
      is likely that interference with the structure and conformation of selected
      domains of platelet membrane proteins might be the crucial mechanism by which
      EDTA leads to exaggerated activation of platelets in whole blood.

PMID- 16793757
TI  - Characterization of adhesive and aggregating functions of pig platelets:
      comparative studies with human platelets and differential effects of calcium
      chelation.
AB  - We have characterized functional responses of pig platelets in citrate
      anticoagulated blood and compared results with those of human platelets. Platelet
      aggregation was induced with known activating agents using citrated platelet-rich
      plasma. Adhesive and cohesive functions of platelets were evaluated using a
      perfusion flow system with whole anticoagulated blood (10 min, 800/s). To test
      the differential sensitivity to free calcium levels, two citrate concentrations
      (19 mM [standard] vs 13 mM) were used as anticoagulants. The ability of platelets
      to produce thromboxane A2 was also quantified, using radioimmunoassay. In the
      presence of 19 mM citrate concentration, pig platelets responded poorly to ADP
      and collagen, and did not respond to arachidonic acid and U46619. Pig platelets
      adhered well onto subendothelium, but failed to form aggregates on previously
      spreaded platelets. At 13 mM citrate concentration, the aggregating responses of
      pig platelets improved, but some of the aggregation patterns were still
      reversible. The lower citrate concentration had a dramatic impact on perfusion
      studies, where the formation of platelet aggregates was restored up to levels
      found in humans. Thromboxane levels in pig serum were only 20 to 30% of that
      found in humans. So, pig platelets possess functional properties that clearly
      differ from human platelets: they are more sensitive to the calcium chelating
      effects of citrate. Arachidonic acid metabolism and thromboxane amplification of
      platelet responses seem less preponderant in the pig species.

PMID- 16793758
TI  - Effect of hypochlorite (HOCl)-modified low density lipoproteins and high density
      lipoproteins on platelet function.
AB  - As hypochlorous acid (HOCl) might be a potential candidate for generation of
      modified (lipo)proteins in vivo , the present study was aimed at investigating
      the effects of HOCl-modified lipoproteins on platelet function in vitro.
      Lipoproteins modified with HOCl at concentrations that occur physiologically did
      not induce spontaneous platelet aggregation. However, low density lipoproteins
      (LDL; 100 to 500 microg protein/ml) increased platelet aggregation and
      fluorescence anisotropy in response to ADP (1 and 10 microM) and thrombin (0.1
      and 0.5 U/ml) as well as malondialdehyde (MDA) formation as a function of
      increasing HOCl-concentrations (0.2 to 1.6 mM). HOCl-modified high density
      lipoprotein subfraction 3 (HDL3) had no effect on platelet function.

PMID- 16793759
TI  - Survey of training in geriatric medicine in UK undergraduate medical schools.

PMID- 16793760
TI  - Wnt signaling: multiple pathways, multiple receptors, and multiple transcription
      factors.

PMID- 16793761
TI  - Mammalian zinc transport, trafficking, and signals.

PMID- 16793762
TI  - When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?:
      Insights into the regulation of ceramide synthesis.

PMID- 16793763
TI  - The alpha1-beta-subunit interaction that modulates calcium channel activity is
      reversible and requires a competent alpha-interaction domain.
AB  - High voltage-gated calcium channels consist of a pore-forming subunit (alpha(1))
      and three nonhomologous subunits (alpha(2)/delta, beta, and gamma). Although it
      is well established that the beta-subunit promotes traffic of channels to the
      plasma membrane and modifies their activity, the reversible nature of the
      interaction with the alpha(1)-subunit remains controversial. Here, we address
      this issue by examining the effect of purified beta(2a) protein on Ca(V)1.2 and
      Ca(V)2.3 channels expressed in Xenopus oocytes. The beta(2a)-subunit binds to the
      alpha(1)-interaction domain (AID) in vitro, and when injected into oocytes, it
      shifts the voltage dependence of activation and increases charge movement to
      ionic current coupling of Ca(V)1.2 channels. This increase depended on the
      integrity of AID but was not abolished by bafilomycin, demonstrating that the
      alpha(1)-beta interaction through the AID site can take place at the plasma
      membrane. Furthermore, injection of beta(2a) protein inhibited inactivation of
      Ca(V)2.3 channels and converted fast inactivating Ca(V)2.3/beta(1b) channels to
      slow inactivating channels. Inhibition of inactivation required larger
      concentration of beta(2a) in oocytes expressing Ca(V)2.3/beta(1b) channels than
      expressing Ca(V)2.3 alone but reached the same maximal level as expected for a
      competitive interaction through a single binding site. Together, our data show
      that the alpha(1)-beta interaction is reversible in intact cells and defines
      calcium channels beta-subunits as regulatory proteins rather than stoichiometric
      subunits.

PMID- 16793764
TI  - Role of the activation loop tyrosines in regulation of the insulin-like growth
      factor I receptor-tyrosine kinase.
AB  - The tyrosine kinase activity of insulin-like growth factor I receptor (IGF1R) is
      under tight control. Ligand binding to the extracellular portion of IGF1R
      stimulates autophosphorylation at three sites (Tyr1131, Tyr1135, and Tyr1136) in
      the activation loop within the tyrosine kinase catalytic domain.
      Autophosphorylation at all three sites is required for maximum enzyme activity,
      and for IGF1-stimulated cellular activity of the receptor. Previous studies have
      not clarified the contributions of the individual tyrosines to enzymatic
      activation. Here, we produced single Tyr-to-Phe mutations at these positions, and
      compared activities of the purified kinase domains (unphosphorylated and
      phosphorylated) with wild-type IGF1R. Rates of autophosphorylation of the three
      mutants were more rapid than for wild-type IGF1R; this was most apparent for the
      Y1135F mutant. Substrate phosphorylation studies on the unphosphorylated forms of
      IGF1R confirmed that the value of Vmax for Y1135F was elevated relative to wild
      type IGF1R, consistent with a disruption of an autoinhibitory interaction. In
      contrast, activity measurements on the fully phosphorylated enzymes indicated
      that kcat/Km values were lowered relative to wild-type IGF1R; this effect was
      most dramatic for Y1136F. We confirmed these findings using limited proteolysis
      and tryptophan fluorescence experiments. The results demonstrate that Tyr1135
      plays a particularly important role in stabilizing the autoinhibited conformation
      of the activation loop, while Tyr1136 plays the key role in stabilizing the open,
      activated conformation of IGF1R.

PMID- 16793765
TI  - The crystal structure of iron-free human serum transferrin provides insight into
      inter-lobe communication and receptor binding.
AB  - Serum transferrin reversibly binds iron in each of two lobes and delivers it to
      cells by a receptor-mediated, pH-dependent process. The binding and release of
      iron result in a large conformational change in which two subdomains in each lobe
      close or open with a rigid twisting motion around a hinge. We report the
      structure of human serum transferrin (hTF) lacking iron (apo-hTF), which was
      independently determined by two methods: 1) the crystal structure of recombinant
      non-glycosylated apo-hTF was solved at 2.7-A resolution using a multiple
      wavelength anomalous dispersion phasing strategy, by substituting the nine
      methionines in hTF with selenomethionine and 2) the structure of glycosylated apo
      hTF (isolated from serum) was determined to a resolution of 2.7A by molecular
      replacement using the human apo-N-lobe and the rabbit holo-C1-subdomain as search
      models. These two crystal structures are essentially identical. They represent
      the first published model for full-length human transferrin and reveal that, in
      contrast to family members (human lactoferrin and hen ovotransferrin), both lobes
      are almost equally open: 59.4 degrees and 49.5 degrees rotations are required to
      open the N- and C-lobes, respectively (compared with closed pig TF). Availability
      of this structure is critical to a complete understanding of the metal binding
      properties of each lobe of hTF; the apo-hTF structure suggests that differences
      in the hinge regions of the N- and C-lobes may influence the rates of iron
      binding and release. In addition, we evaluate potential interactions between apo
      hTF and the human transferrin receptor.

PMID- 16793766
TI  - MAPKAPK-2 is a critical signaling intermediate in NHE3 activation following Na+
      glucose cotransport.
AB  - Villus enterocyte nutrient absorption occurs via precisely orchestrated
      interactions among multiple transporters. For example, transport by the apical
      Na(+)-glucose cotransporter, SGLT1, triggers translocation of NHE3, Na(+)-H(+)
      antiporter isoform 3, to the plasma membrane. This translocation requires
      activation of p38 mitogen-activated protein kinase (MAPK), Akt2, and ezrin. Akt2
      directly phosphorylates ezrin, but the precise role of p38 MAPK in this process
      remains to be defined. Sequence analysis suggested that p38 MAPK could not
      directly phosphorylate Akt2. We hypothesized that MAPKAPK-2 might link p38 MAPK
      and Akt2 activation. MAPKAPK-2 was phosphorylated after initiation of Na(+)
      glucose cotransport with kinetics that paralleled activation of p38 MAPK, Akt2,
      and ezrin. MAPKAPK-2, Akt2, and ezrin phosphorylation were all attenuated by p38
      MAPK inhibition but were unaffected by dominant negative ezrin expression. Akt2
      inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation,
      suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK-dependent Akt2
      activation. Consistent with this, MAP-KAPK-2 could phosphorylate an Akt2-derived
      peptide in vitro. siRNA-mediated MAPKAPK-2 knockdown inhibited phosphorylation of
      Akt2 and ezrin but not p38 MAPK. MAPKAPK-2 knockdown also blocked NHE3
      translocation. Thus, MAP-KAPK-2 controls Akt2 phosphorylation. In so doing, MAP
      KAPK-2 links p38 MAPK to Akt2, ezrin, and NHE3 activation after SGLT1-mediated
      transport.

PMID- 16793767
TI  - Archaeal proteasomes effectively degrade aggregation-prone proteins and reduce
      cellular toxicities in mammalian cells.
AB  - The 20 S proteasome is a ubiquitous, barrel-shaped protease complex responsible
      for most of cellular proteolysis, and its reduced activity is thought to be
      associated with accumulations of aberrant or misfolded proteins, resulting in a
      number of neurodegenerative diseases, including amyotrophic lateral sclerosis,
      spinal and bulbar muscular atrophy, Parkinson disease, and Alzheimer disease. The
      20 S proteasomes of archaebacteria (archaea) are structurally simple and
      proteolytically powerful and thought to be an evolutionary precursor to
      eukaryotic proteasomes. We successfully reproduced the archaeal proteasome in a
      functional state in mammalian cells, and here we show that the archaeal
      proteasome effectively accelerated species-specific degradation of mutant
      superoxide dismutase-1 and the mutant polyglutamine tract-extended androgen
      receptor, causative proteins of familial amyotrophic lateral sclerosis and spinal
      and bulbar muscular atrophy, respectively, and reduced the cellular toxicities of
      these mutant proteins. Further, we demonstrate that archaeal proteasome can also
      degrade other neurodegenerative disease-associated proteins such as alpha
      synuclein and tau. Our study showed that archaeal proteasomes can degrade
      aggregation-prone proteins whose toxic gain of function causes neurodegradation
      and reduce protein cellular toxicity.

PMID- 16793768
TI  - Different domains of the AMPA receptor direct stargazin-mediated trafficking and
      stargazin-mediated modulation of kinetics.
AB  - Stargazin is an accessory protein of AMPA receptors that enhances surface
      expression and also affects the biophysical properties of the receptor. AMPA
      receptor domains necessary for either of these two processes have not yet been
      identified. Here, we used confocal imaging and electrophysiology of
      heterologously expressed, fluorophore-tagged GluR1, GluR2, and stargazin to study
      surface expression and desensitization kinetics. Stargazin-mediated trafficking
      was sensitive to the nature of the AMPA receptor cytoplasmic domain. The
      insertion of YFP after residue 15 of the truncated cytoplasmic tail of GluR1i
      perturbed stargazin-mediated trafficking of the receptor but not its modulation
      of desensitization kinetics. This construct also failed to permit fluorescence
      resonance energy transfer (FRET) with stargazin in the endoplasmic reticulum
      (ER), whereas FRET between fluorophore-tagged stargazin and non-truncated AMPA
      receptors demonstrated a specific interaction between these proteins, both in the
      ER and the plasma membrane. Rather than encoding a specific binding site, the
      fluorophore-tagged C terminus may restrict access to one or more ER retention
      sites. Although perturbations of the C terminus impeded stargazin-mediated
      trafficking to the plasma membrane, the effects of stargazin on the biophysical
      properties of AMPA receptors (i.e. modulation of desensitization) remained
      intact. These data provide strong evidence that the AMPA receptor domains
      required for stargazin modulation of gating and trafficking are separable.

PMID- 16793769
TI  - In vivo targeting of the yeast Pop2 deadenylase subunit to reporter transcripts
      induces their rapid degradation and generates new decay intermediates.
AB  - Deadenylation is the rate-limiting step of mRNA decay, yet little is known about
      the mechanism regulating this process. In yeast, deadenylation is mainly mediated
      by the Pop2-Ccr4 complex. We tested whether the selective recruitment of this
      deadenylase to target mRNAs was sufficient to stimulate their decay in vivo. For
      this purpose, the Pop2 factor was fused to a U1A RNA binding domain while U1A
      binding sites were inserted in untranslated regions of a reporter transcript.
      Analysis of the reporter fate in strains expressing the Pop2-U1A-RBD fusion
      demonstrated a specific activation of target mRNA decay. Increased mRNA
      degradation involved accumulation of deadenylated mRNAs that was not detected
      when the control factors Dcp2 or Pub1 were tethered to the same transcript. The
      rapid target mRNA degradation was also accompanied by the appearance of new decay
      intermediates generated by the 3' -5' trimming of the corresponding 3' 
      untranslated region. Interestingly, this process was not mediated by the exosome
      but may result from the activity of the Pop2-Ccr4 deadenylase itself. These
      results indicate that selective recruitment of the Pop2-Ccr4 deadenylase is
      sufficient to activate mRNA decay, even though this process can also be
      stimulated by additional mechanisms. Furthermore, deadenylase recruitment affects
      the downstream path of mRNA decay.

PMID- 16793770
TI  - Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce
      apoptosis in human prostate cancer cells by IGF-independent mechanisms without
      being concentrated in the nucleus.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3), a secreted protein, has
      the intrinsic ability to induce apoptosis directly without binding insulin-like
      growth factors. Previous studies suggested that IGFBP-3 must be secreted to exert
      its biological functions. IGFBP-3 contains a nuclear localization signal (NLS),
      and exogenous IGFBP-3 is translocated into the nucleus, suggesting that both
      secretion and nuclear localization may play important roles in IGFBP-3 action. To
      address these questions, we fused yellow fluorescent protein (YFP) to mature
      IGFBP-3 lacking its signal peptide so that it would remain intracellular and
      mutated the C-terminal NLS of IGFBP-3, (228)KGRKR(232), to MDGEA. Following
      transfection of PC-3 human prostate cancer cells with these constructs, Western
      blots indicated that YFP-IGFBP-3 lacking a signal peptide was cell-associated and
      not present in the extracellular media. Moreover, the fusion protein was not N
      glycosylated, indicating that it had not entered the secretory pathway. Confocal
      imaging showed that intracellular YFP-MDGEA-IGFBP-3 was predominantly
      cytoplasmic. Transient transfection of nonsecreted YFP-wild-type IGFBP-3
      decreased cell viability, as assessed by staining with annexin V followed by flow
      cytometry. Induction of cell death was caspase-dependent, indicative of
      apoptosis. Apoptosis also was induced by the nonsecreted NLS mutant (YFP-MDGEA
      IGFBP-3) alone and when the IGF-binding site also had been mutated. These results
      indicate that IGFBP-3 can induce apoptosis in an IGF-independent manner without
      being secreted or concentrated in the nucleus.

PMID- 16793771
TI  - Properties of human IgG1s engineered for enhanced binding to the neonatal Fc
      receptor (FcRn).
AB  - We describe here the functional implications of an increase in IgG binding to the
      neonatal Fc receptor. We have defined in a systematic fashion the relationship
      between enhanced FcRn binding of a humanized anti-respiratory syncytial virus
      (RSV) monoclonal antibody (MEDI-524) and the corresponding biological
      consequences in cynomolgus monkeys. The triple mutation M252Y/S254T/T256E (YTE)
      was introduced into the Fc portion of MEDI-524. Whereas these substitutions did
      not affect the ability of MEDI-524 to bind to its cognate antigen and inhibit RSV
      replication, they resulted in a 10-fold increase in its binding to both
      cynomolgus monkey and human FcRn at pH 6.0. MEDI-524-YTE was efficiently released
      from FcRn at pH 7.4 in both cases. We show that MEDI-524-YTE consistently
      exhibited a nearly 4-fold increase in serum half-life in cynomolgus monkeys when
      compared with MEDI-524. This constituted the largest half-life improvement
      described to date for an IgG in a primate. For the first time, we demonstrate
      that these sustained serum levels resulted in an up to 4-fold increase in lung
      bioavailability. Importantly, we also establish that our non-human primate model
      is relevant to human. Finally, we report that the YTE triple substitution
      provided a means to modulate the antibody-dependent cell-mediated cytotoxicity
      (ADCC) activity of a humanized IgG1 directed against the human integrin
      alpha(v)beta3. Therefore, the YTE substitutions allow the simultaneous modulation
      of serum half-life, tissue distribution and activity of a given human IgG1.

PMID- 16793772
TI  - Non-B DNA conformations formed by long repeating tracts of myotonic dystrophy
      type 1, myotonic dystrophy type 2, and Friedreich's ataxia genes, not the
      sequences per se, promote mutagenesis in flanking regions.
AB  - The expansions of long repeating tracts of CTG.CAG, CCTG.CAGG, and GAA.TTC are
      integral to the etiology of myotonic dystrophy type 1 (DM1), myotonic dystrophy
      type 2 (DM2), and Friedreich's ataxia (FRDA). Essentially all studies on the
      molecular mechanisms of this expansion process invoke an important role for non-B
      DNA conformations which may be adopted by these repeat sequences. We have
      directly evaluated the role(s) of the repeating sequences per se, or of the non-B
      DNA conformations formed by these sequences, in the mutagenic process. Studies in
      Escherichia coli and three types of mammalian (COS-7, CV-1, and HEK-293)
      fibroblast-like cells revealed that conditions which promoted the formation of
      the non-B DNA structures enhanced the genetic instabilities, both within the
      repeat sequences and in the flanking sequences of up to approximately 4 kbp. The
      three strategies utilized included: the in vivo modulation of global negative
      supercoil density using topA and gyrB mutant E. coli strains; the in vivo
      cleavage of hairpin loops, which are an obligate consequence of slipped-strand
      structures, cruciforms, and intramolecular triplexes, by inactivation of the SbcC
      protein; and by genetic instability studies with plasmids containing long
      repeating sequence inserts that do, and do not, adopt non-B DNA structures in
      vitro. Hence, non-B DNA conformations are critical for these mutagenesis
      mechanisms.

PMID- 16793773
TI  - Stepped changes of monovalent ligand-binding force during ligand-induced
      clustering of integrin alphaIIB beta3.
AB  - Recent evidence demonstrated that conformational changes of the integrin during
      receptor activation affected its binding to extracellular matrix; however,
      experimental assessment of ligand-receptor binding following the initial
      molecular interaction has rarely been carried out at a single-molecule
      resolution. In the present study, laser tweezers were used to measure the binding
      force exerted by a live Chinese hamster ovary cell that expressed integrin
      alphaIIb beta3 (CHO alphaIIb beta3), to the bead carrier coated with the snake
      venom rhodostomin that served as an activated ligand for integrin alphaIIb beta3.
      A progressive increase of total binding force over time was noticed when the bead
      interacted with the CHO alphaIIb beta3 cell; such an increase was due mainly to
      the recruitment of more integrin molecules to the bead-cell interface. When the
      binding strength exerted by a single ligand-receptor pair was derived from the
      "polyvalent" measurements, surprisingly, a stepped decrease of the "monovalent
      binding force" was noted (from 4.15 to 2.54 piconewtons (pN)); such decrease
      appeared to occur during the ligand-induced integrin clustering process. On the
      other hand, the mutant rhodostomin defective in clustering integrins exhibited
      only one (1.81 pN) unit binding strength.

PMID- 16793774
TI  - Rapid ATP-dependent deadenylation of nanos mRNA in a cell-free system from
      Drosophila embryos.
AB  - Shortening of the poly(A) tail (deadenylation) is the first and often rate
      limiting step in the degradation pathway of most eukaryotic mRNAs and is also
      used as a means of translational repression, in particular in early embryonic
      development. The nanos mRNA is translationally repressed by the protein Smaug in
      Drosophila embryos. The RNA has a short poly(A) tail at steady state and decays
      gradually during the first 2-3 h of development. Smaug has recently also been
      implicated in mRNA deadenylation. To study the mechanism of sequence-dependent
      deadenylation, we have developed a cell-free system from Drosophila embryos that
      displays rapid deadenylation of nanos mRNA. The Smaug response elements contained
      in the nanos 3'-untranslated region are necessary and sufficient to induce
      deadenylation; thus, Smaug is likely to be involved. Unexpectedly, deadenylation
      requires the presence of an ATP regenerating system. The activity can be pelleted
      by ultracentrifugation, and both the Smaug protein and the CCR4.NOT complex, a
      known deadenylase, are enriched in the active fraction. The same extracts show
      pronounced translational repression mediated by the Smaug response elements. RNAs
      lacking a poly(A) tail are poorly translated in the extract; therefore, SRE
      dependent deadenylation contributes to translational repression. However,
      repression is strong even with RNAs either bearing a poly(A) tract that cannot be
      removed or lacking poly(A) altogether; thus, an additional aspect of
      translational repression functions independently of deadenylation.

PMID- 16793775
TI  - The essential role of the death domain kinase receptor-interacting protein in
      insulin growth factor-I-induced c-Jun N-terminal kinase activation.
AB  - Insulin-like growth factor I (IGF-I) plays an important role in cell survival,
      proliferation, and differentiation. Diverse kinases, including AKT/protein kinase
      B, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase
      (JNK), can be activated by IGF-I. Here, we show that the receptor-interacting
      protein (RIP), a key mediator of tumor necrosis factor-induced NF-kappaB and JNK
      activation, plays a key role in IGF-I receptor signaling. IGF-I induced a robust
      JNK activation in wild type but not RIP null (RIP-/-) mouse embryonic fibroblast
      cells. Reconstitution of RIP expression in the RIP-/- cells restored the
      induction of JNK by IGF-I, suggesting that RIP is essential in IGF-I-induced JNK
      activation. Reconstitution experiments with different RIP mutants further
      revealed that the death domain and the kinase activity of RIP are not required
      for IGF-I-induced JNK activation. Interestingly, the AKT and ERK activation by
      IGF-I was normal in RIP-/- cells. The phosphatidylinositol 3-kinase inhibitor,
      wortmannin, did not affect IGF-I-induced JNK activation. These results agree with
      previous studies showing that the IGF-I-induced JNK activation pathway is
      distinct from that of ERK and AKT activation. Additionally, physical interaction
      of ectopically expressed RIP and IGF-IRbeta was detected by co
      immunoprecipitation assays. More importantly, RIP was recruited to the IGF-I
      receptor complex during IGF-I-induced signaling. Furthermore, we found that IGF-I
      induced cell proliferation was impaired in RIP-/- cells. Taken together, our
      results indicate that RIP, a key factor in tumor necrosis factor signaling, also
      plays a pivotal role in IGF-I-induced JNK activation and cell proliferation.

PMID- 16793776
TI  - Ca2+ and Mg2+ binding properties of GCAP-1. Evidence that Mg2+-bound form is the
      physiological activator of photoreceptor guanylyl cyclase.
AB  - Guanylyl cyclase-activating protein 1 (GCAP-1) is an EF-hand protein that
      activates retinal guanylyl cyclase (RetGC) in photoreceptors at low free Ca2+ in
      the light and inhibits it in the dark when Ca2+ concentrations rise. We present
      the first direct evidence that Mg2+-bound form of GCAP-1, not its cation-free
      form, is the true activator of RetGC-1 under physiological conditions. Of four EF
      hand structures in GCAP-1, three bound Ca2+ ions and could exchange Ca2+ for
      Mg2+. At concentrations of free Ca2+ and Mg2+ typical for the light-adapted
      photoreceptors, all three metal-binding EF-hands were predominantly occupied by
      Mg2, and the presence of bound Mg2+ in GCAP-1 was essential for its ability to
      stimulate RetGC-1. In the Mg2+-bound form of GCAP-1 all three Trp residues became
      more exposed to the polar environment compared with its apo form. The replacement
      of Mg2+ by Ca2+ in the EF-hands 2 and 3 further exposed Trp-21 to the solution in
      a non-metal-binding EF-hand domain 1 that interacts with RetGC. Contrary to that,
      replacement of Mg2+ by Ca2+ in the EF-hand 4 moved Trp-94 in the entering alpha
      helix of the EF-hand 3 back to the non-polar environment. Our results demonstrate
      that Mg2+ regulates GCAP-1 not only by adjusting its Ca2+ sensitivity to the
      physiological conditions in photoreceptors but also by creating the conformation
      required for RetGC stimulation.

PMID- 16793777
TI  - Inhibition of glutamate transporters increases the minimum alveolar concentration
      for isoflurane in rats.
AB  - BACKGROUND: Glutamate transporters [also named excitatory amino acid transporters
      (EAATs)] bind and take up extracellular glutamate, a major excitatory
      neurotransmitter, and can regulate glutamatergic neurotransmission in synapses.
      As anaesthesia is proposed to be induced by enhancing inhibitory
      neurotransmission, inhibiting excitatory neurotransmission, or both we
      hypothesize that inhibition of EAAT activity can increase the anaesthetic
      requirement. METHODS: The minimum alveolar concentration (MAC, the anaesthetic
      concentration required to suppress movement in response to noxious stimulation in
      50% of subjects) for isoflurane was determined in adult male Sprague-Dawley rats
      after intrathecal administration of EAAT inhibitors. RESULTS: Application of DL
      threo-beta-benzyloxyaspartate, a selective EAAT inhibitor, dose- and time
      dependently increased the MAC for isoflurane. The MAC was 109 (1)% and 116 (4)%
      of the baseline, respectively, for 0.2 and 0.4 micromol of DL-threo-beta
      benzyloxyaspartate 15 min after the injection of the drug (n=5, P<0.05 compared
      with the baseline MAC). Intrathecal injection of dihydrokainate, a selective
      inhibitor of EAAT type 2, also increased the MAC for isoflurane. CONCLUSIONS:
      These results suggest that EAAT in the spinal cord can regulate the requirement
      of isoflurane to induce immobility. EAAT2 may be involved in this effect.

PMID- 16793778
TI  - Myocardial protection with volatile anaesthetic agents during coronary artery
      bypass surgery: a meta-analysis.
AB  - Previous studies have investigated the role of volatile anaesthetic agents in
      myocardial protection during coronary artery bypass graft (CABG) surgery, and
      some have identified beneficial effects. However, these studies have been too
      small to identify a significant effect on myocardial infarction (MI) or
      mortality. We undertook a systematic overview and meta-analysis of all randomized
      trials comparing volatile with non-volatile anaesthesia in CABG surgery. We
      identified 27 trials that included 2979 patients. There was no significant
      difference in myocardial ischaemia, MI, intensive care unit length of stay or
      hospital mortality between the groups (all P>0.05). Post-bypass, patients
      randomized to receive volatile anaesthetics had 20% higher cardiac indices
      (P=0.006), significantly lower troponin I serum concentrations (P=0.002) and
      lesser requirement for inotropic support (P=0.004) compared with those randomized
      to receive i.v. anaesthetics. Duration of mechanical ventilation was reduced by
      2.7 h (P=0.04), and there was a 1 day decrease in hospital length of stay
      (P<0.001). Some of these outcomes were based on a smaller number of trials
      because of incomplete data, largely because the individual trials focused on one
      or more surrogate endpoints. We found some evidence that volatile anaesthetic
      agents provide myocardial protection in CABG surgery, but larger adequately
      powered trials with agreed, defined outcomes need to be done to fully assess a
      possible beneficial effect of volatile anaesthetic agents on the risk of MI and
      mortality.

PMID- 16793779
TI  - Xenon preconditioning differently regulates p44/42 MAPK (ERK 1/2) and p46/54 MAPK
      (JNK 1/2 and 3) in vivo.
AB  - BACKGROUND: Xenon (Xe) induces preconditioning (PC) of the rat heart in vivo via
      activation of p38 mitogen-activated protein kinase (MAPK). The role of ERK 1/2
      and JNK 1/2 and 3 in Xe-PC has yet not been determined. METHODS: For infarct size
      measurements, anaesthetized rats were subjected to 25 min of coronary artery
      occlusion followed by 120 min of reperfusion. Animals received Xe 70% during
      three 5 min periods with and without the ERK inhibitor PD 98059 (1 mg kg(-1), PD)
      or the JNK inhibitor SP 600125 (6 mg kg(-1), SP) (n=10 per group). Additional
      hearts were excised for western blot and kinase activity assay: without further
      treatment, after the first, the second and the third period of Xe-PC or at the
      end of the last washout phase (n=4 each). RESULTS: Infarct size (% of area at
      risk) was reduced from 46.2 (8.1)% to 28.4 (11.3)% after Xe-PC (P<0.01). PD
      completely abolished this effect [49.7 (11.4)%, P<0.01 vs Xe-PC]. The ratio of
      particulate/cytosolic phospho ERK 1/2 was time dependently increased during the
      PC protocol [ERK 1: 15 min: 2.4 (1.2), 25 min: 1.5 (0.3), 35 min: 1.6 (0.7), 45
      min: 1.5 (0.5) vs Con 1.0 (0.5) and ERK 2: 15 min: 3.3 (1.8), 25 min: 2.0 (1.5),
      35 min: 1.8 (1.7), 45 min: 0.9 (0.6) vs Con 0.8 (0.4)]. This finding was
      confirmed by a non-radioactive MAPK activity assay. In contrast SP had no effect
      on Xe-PC and the phosphorylation state of JNK was not influenced by Xe-PC.
      CONCLUSION: Besides the p38 MAPK, ERK 1/2 also is a mediator of Xe-PC. However,
      JNK is not involved, demonstrating a highly specific regulation of different
      kinases during Xe-PC.

PMID- 16793780
TI  - Influence of a 30-min break on divided attention and working memory in resident
      anaesthetists on daily routine.
AB  - BACKGROUND: The aim of this study is to test the hypothesis that a standard 30
      min break in a routine 7.5 h period of work makes a difference in cognitive
      function. METHODS: In a double-blinded, cross-over trial 30 residents in
      anaesthesia were randomized to receive or not to receive a 30-min break between
      the assessment times of 07:30 and 14:00. in a normal working day. After at least
      28 days the test was repeated with each resident in the opposite group. Primary
      outcome measure was the Test for Attentional Performance with the subtest of
      working memory and divided attention. Secondary outcomes are the Stanford
      Sleepiness Scale and the State-Trait Anxiety Inventory test. RESULTS: The sleep,
      caffeine and nicotine habits in both groups were comparable. There was no
      difference between the two groups in the Test for Attentional Performance,
      Stanford Sleepiness Scale and the State-Trait Anxiety Inventory. The correlation
      between recovery through sleep and sleep disturbance in the night before
      investigation to the Stanford Sleepiness Scale (P<0.001 and P=0.003) and State
      Trait Anxiety Inventory (P<0.001 and P=0.001) at the 07:30 assessment is
      significant. For the 14:00 assessment the only significant correlation is between
      the recovery through sleep with the Stanford Sleepiness Scale (P=0.04) and the
      State-Trait Anxiety Inventory (P=0.05). CONCLUSION: A 30-min break during a 7.5 h
      daily routine did not influence cognitive function tests.

PMID- 16793781
TI  - Length of insertion for pulmonary artery catheters to locate different cardiac
      chambers in patients undergoing cardiac surgery.
AB  - BACKGROUND: Although, guidelines related to length of insertion of a pulmonary
      artery catheter to reach a particular cardiac chamber are available, these are
      not backed by clinical studies. We measured the length of insertion of pulmonary
      artery catheters to locate the right ventricle, pulmonary artery and pulmonary
      capillary wedge positions in 300 adult patients undergoing elective cardiac
      surgery. METHODS: The pulmonary artery catheters were inserted using a standard
      technique through the right internal jugular vein. The right ventricle, pulmonary
      artery and wedge position of the catheter were confirmed by the characteristic
      waveforms, and the length of insertion to these points was measured. RESULTS: The
      right ventricle was reached at 24.6 (3) cm (95% CI 24.2-24.9 cm), pulmonary
      artery at 36 (4) cm (95% CI 35.6-36.5 cm) and wedge position at 42.8 (5.7) cm
      (95% CI 42.2-43.5 cm). The length of catheter to reach the right ventricle,
      pulmonary artery and wedge position was significantly more in patients undergoing
      valve surgery as compared with those undergoing coronary artery bypass grafting
      [26 (3.8) and 24 (2.5) cm; 38.5 (4.6) and 35 (3.2) cm; and 47.8 (6.9) and 41.2
      (4.1) cm, respectively, P<0.001]. The length of insertion to reach pulmonary
      artery and pulmonary capillary wedge position was directly related to height of
      the patient (Pearson's correlation 0.157 and 0.15, respectively). CONCLUSIONS: We
      have provided the norms related to length of insertion of pulmonary artery
      catheter, which should be useful in accurate placement of the catheter and
      minimize complications related to coiling of the catheter.

PMID- 16793782
TI  - Anticoagulant-induced pseudothrombocytopenia occurring after transcatheter
      arterial embolization for hepatocellular carcinoma.
AB  - Pseudothrombocytopenia (PTCP) is the in vitro phenomenon of anticoagulant
      activated platelet agglutination that results in spuriously low platelet counts.
      We report the case of a 65-year-old man with EDTA- and sodium citrate-dependent
      PTCP occurring after transcatheter arterial embolization (TAE) for hepatocellular
      carcinoma (HCC) due to hepatitis C cirrhosis. Invasion of the portal and hepatic
      veins by HCC formed severe trans-tumoral arterio-venous shunts that were
      effectively treated by TAE. Two days after the therapy, PTCP was seen on blood
      count and continued for 4 months. The patient received unnecessary treatment for
      disseminated intravascular coagulation (DIC) until the diagnosis of PTCP was
      established. PTCP is a rare complication but should be considered after TAE for
      HCC; lack of recognition may lead the physician to misdiagnosis and patient
      mismanagement.

PMID- 16793783
TI  - Patients' own assessments of quality of primary care compared with objective
      records based measures of technical quality of care: cross sectional study.
AB  - OBJECTIVE: To investigate the relation between older patients' assessments of the
      quality of their primary care and measures of good clinical practice on the basis
      of data from administrative and clinical records. DESIGN: Cross sectional
      population based study using the general practice assessment survey. SETTING: 18
      general practices in the Basildon primary care trust area, south east England.
      PARTICIPANTS: 3487 people aged 65 or more. MAIN OUTCOME MEASURES: Correlations
      between mean practice scores on the general practice assessment survey and three
      evidence based measures on survey of case records (monitoring for, and control
      of, hypertension, and vaccination against influenza). RESULTS: 76% of people
      (3487/4563) responded to the general practice assessment survey. Correlations
      between patient assessed survey scores for technical quality and the objective
      records based measures of good clinical practice were 0.22 (95% confidence
      interval -0.28 to 0.62) for hypertension monitored, 0.30 (-0.19 to 0.67) for
      hypertension controlled, and -0.05 (-0.50 to 0.43) for influenza vaccination.
      CONCLUSIONS: Older patients' assessments are not a sufficient basis for assessing
      the technical quality of their primary care. For an overall assessment both
      patient based and records based measures are required.

PMID- 16793784
TI  - Drugs for anovulatory infertility in polycystic ovary syndrome.

PMID- 16793785
TI  - Doctors, interrogation, and torture.

PMID- 16793786
TI  - The diagnosis and treatment of carpal tunnel syndrome.

PMID- 16793787
TI  - Rational prescribing for children.

PMID- 16793788
TI  - Ketamine: a misunderstood analgesic?

PMID- 16793790
TI  - England sets up task force to hasten use of electronic records.

PMID- 16793791
TI  - US campaign to save 100,000 lives exceeds its target.

PMID- 16793792
TI  - Overtaxed US emergency care system needs reorganisation.

PMID- 16793793
TI  - Canada may be forced to allow direct to consumer advertising.

PMID- 16793795
TI  - California will be only state to meet government target on smoking.

PMID- 16793797
TI  - Improving safety could save 15,000 children's lives a year in Europe, says WHO.

PMID- 16793800
TI  - BMA's claim of unemployment among junior doctors is rejected.

PMID- 16793802
TI  - UK needs 10,000 extra psychologists.

PMID- 16793801
TI  - Address poverty to reduce mental health problems among children, says BMA.

PMID- 16793804
TI  - Defence ministry denies ignoring Gulf war syndrome in pension award.

PMID- 16793806
TI  - Cholera outbreak in Darfur is made worse by advent of rains.

PMID- 16793807
TI  - Dutch health minister orders probe into influence of industry on medical
      guidelines.

PMID- 16793809
TI  - An eye opening technique.

PMID- 16793810
TI  - Effect of perioperative beta blockade in patients with diabetes undergoing major
      non-cardiac surgery: randomised placebo controlled, blinded multicentre trial.
AB  - OBJECTIVES: To evaluate the long term effects of perioperative beta blockade on
      mortality and cardiac morbidity in patients with diabetes undergoing major non
      cardiac surgery. DESIGN: Randomised placebo controlled and blinded multicentre
      trial. Analyses were by intention to treat. SETTING: University anaesthesia and
      surgical centres and one coordinating centre. PARTICIPANTS: 921 patients aged >
      39 scheduled for major non-cardiac surgery. INTERVENTIONS: 100 mg metoprolol
      controlled and extended release or placebo administered from the day before
      surgery to a maximum of eight perioperative days. MAIN OUTCOME MEASURES: The
      composite primary outcome measure was time to all cause mortality, acute
      myocardial infarction, unstable angina, or congestive heart failure. Secondary
      outcome measures were time to all cause mortality, cardiac mortality, and non
      fatal cardiac morbidity. RESULTS: Mean duration of intervention was 4.6 days in
      the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly
      reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean
      blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462
      patients in the metoprolol group (21%) and 93 of 459 patients in the placebo
      group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18
      months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group
      and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in
      risk for the proportion of patients with serious adverse events was 2.4% (- 0.8%
      to 5.6%). CONCLUSIONS: Perioperative metoprolol did not significantly affect
      mortality and cardiac morbidity in these patients with diabetes. Confidence
      intervals, however, were wide, and the issue needs reassessment. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN58485613.

PMID- 16793812
TI  - The patient's journey: palliative care--a parent's view.

PMID- 16793811
TI  - Antiretroviral treatment of HIV infected adults.

PMID- 16793814
TI  - ABC of chronic obstructive pulmonary disease. Pharmacological management--oral
      treatment.

PMID- 16793816
TI  - Challenges of training doctors in the new English NHS.

PMID- 16793817
TI  - Dutch perspective.

PMID- 16793818
TI  - Australian perspective.

PMID- 16793819
TI  - Is restricted randomisation necessary?

PMID- 16793820
TI  - Indigenous hepatitis E virus infection in England and Wales.

PMID- 16793822
TI  - Climate change: contraction and convergence: myth and reality.

PMID- 16793823
TI  - It's difficult being green (as in vomit).

PMID- 16793824
TI  - Health research funding: ... while injuries were ignored.

PMID- 16793825
TI  - Health research funding: mental health research continues to be underfunded...

PMID- 16793826
TI  - Improving surveillance for Barrett's oesophagus: better to be looked over than be
      overlooked.

PMID- 16793827
TI  - Gabapentin may cause reversible visual field constriction: GABA transaminase
      inhibitors may cause irreversible visual field loss.

PMID- 16793828
TI  - Gabapentin may cause reversible visual field constriction: learning or
      inattention artefact a more likely explanation.

PMID- 16793829
TI  - New antipsychotic agents are much awaited.

PMID- 16793830
TI  - Switching statins: NICE tool overestimates benefits of statins.

PMID- 16793831
TI  - Switching statins: cost of simvastatin is overestimated.

PMID- 16793832
TI  - Improving surveillance for Barrett's oesophagus: AspECT and BOSS trials provide
      an evidence base.

PMID- 16793833
TI  - Injury from lightning strike while using mobile phone.

PMID- 16793834
TI  - Smoking, Helicobacter pylori, and periodontitis.

PMID- 16793835
TI  - Switching statins: how to do it without tears and to benefit the NHS.

PMID- 16793836
TI  - Measurement and reporting of burden of disease for hepatitis A: results of the
      EUROHEP.NET feasibility survey.
AB  - BACKGROUND: European countries use a wide variety of surveillance systems and
      prevention measures for viral hepatitis. Each system is adapted to the local
      situation and an overview was never mapped out at European level. The EUROHEP.NET
      Project is a European Commission-funded feasibility study for a future network on
      surveillance and prevention of vaccine-preventable hepatitis. We analysed the
      measurement and reporting of burden of disease for hepatitis A (HA) and B (HB) in
      the participating countries. METHODS: Twenty-eight countries were invited to
      participate in this study. An online survey was available from the project's
      website (www.eurohep.net). The questions concerned the organisation of the
      surveillance system, case definition, burden of disease, epidemiology, and
      vaccination strategies. The responses on data sources and the numeric data
      related to burden of disease for HA for the period 1997-2001 were analysed.
      RESULTS: Twenty-two countries completed the survey for hepatitis A. Data on total
      number of hospitalisations and deaths were available from 17 and 18 countries,
      respectively, although sometimes not complete. Data on hospitalisation days,
      number of liver transplants and proportion of these due to HAV were often not
      available. CONCLUSION: Surveillance systems on burden of disease for hepatitis A
      show a wide diversity among the participating countries. The introduction of a
      standardised system of data collection at the European Union level according to
      ICD-10 but respecting the local current practices is a primary need, especially
      for data that should be collected in all countries, like hospitalisation and
      mortality. A link to surveillance databases is also strongly recommended.

PMID- 16793837
TI  - Performance of several decision support tools for determining the need for
      systematic screening of childhood lead poisoning around industrial sites.
AB  - BACKGROUND: Living around industrial sites may expose young children to lead and
      cause elevated blood lead levels (BLLs). Systematic screening for childhood lead
      poisoning is necessarily invasive but may be appropriate, depending on children's
      exposure levels. Our objective was to assess the performance of several decision
      support tools for determining the need for systematic BLL screening in children
      around industrial sites. METHOD: We used several exposure models to predict BLLs:
      the pharmacokinetic model IEUBK, the InVS dose model, and an empirical relation
      (Lewin, 1999) between soil concentrations and BLLs. We tested the BLLs
      (percentage of children with a BLL >100 micro g/l) that they predicted as well as
      threshold levels of soil pollution (200, 400, 500 ppm) for 71 situations for
      which the literature reports both environmental soil concentrations and BLLs in
      children aged 0-6 years. The tools' performance (sensitivity and specificity) was
      assessed by the rate of 'correct' (mass screening or not) decisions, judged
      retrospectively on the basis of measured BLLs, for different tolerated
      percentages of children with elevated BLLs. RESULTS: Decision support systems
      based on soil pollution levels were not adequately protective. The IEUBK and
      (updated) InVS mechanistic exposure models were the most effective in this
      setting. CONCLUSION: Exposure models may provide decision support if sufficient
      data about environmental contamination and dietary intake are available. Absolute
      performance measurement nonetheless remains difficult, in view of the limitations
      of the input data.

PMID- 16793838
TI  - Overweight and obesity related to activities in Portuguese children, 7-9 years.
AB  - BACKGROUND: The purpose of the study was to explore the association among the
      following variables: physical activity, TV, videogames, and obesity. The study
      included a Portuguese random nationally representative sample of 3365 children
      (1610 girls and 1755 boys) 7-9 year olds. METHODS: A general questionnaire was
      completed by the parents of participating children to provide information about
      the hours spent per week watching television, computer use and electronic games,
      and the participation in physical education. Overweight and obesity were
      calculated by using the body mass index (BMI) assessment and the cut-off points
      for overweight (25 kg/m(2)) and obesity (30 kg/m(2)). RESULTS: The data from the
      association between BMI and the independent variables (analysis of variance) were
      only significant for time playing electronic games for boys and girls (P < 0.001;
      P < 0.029). The association between hours of watching TV and BMI was significant
      only for boys (P < 0.016). The results from the logistic regression were only
      significant for electronic games both for boys and girls (P < 0.000; P < 0.000).
      CONCLUSIONS: The results of this study suggest that the time spent playing
      electronic games is associated with obesity. Reducing childhood obesity calls for
      the reduction in sedentary behaviours, and the promotion of a more active
      lifestyle.

PMID- 16793840
TI  - Imaging and serum analysis of immune complex formation of radiolabelled
      infliximab and anti-infliximab in responders and non-responders to therapy for
      rheumatoid arthritis.
AB  - BACKGROUND: Many patients with rheumatoid arthritis are currently successfully
      treated with infliximab (anti-tumour necrosis factor); however, about 30% of the
      patients do not respond to infliximab. One of the postulated hypotheses of not
      responding is the fast clearance of infliximab due to the development of
      infliximab-anti-infliximab complexes. OBJECTIVE: To investigate the in vivo
      mechanism of not responding and the role of human anti-chimeric antibodies
      (HACAs) by using radiolabelled infliximab. METHODS: Two responding and two non
      responding patients with rheumatoid arthritis, infused with radiolabelled
      infliximab, were investigated by both imaging and serum analysis. RESULTS: Images
      showed predominant presence of infliximab in blood up to 24 h, with a trend of
      faster blood clearance and of higher liver/spleen uptake in a non-responding
      patient. Clinically inflamed joints showed uptake of the drug. The HACA level in
      the non-responders was high (1641 and 1008 U/ml), but low or not detectable in
      responders. Sucrose gradients of serum showed antibody complexes in both non
      responders. Various sizes of antibody complexes, including very large ones, were
      observed in a non-responder who developed a serious infusion reaction.
      CONCLUSION: Formation of infliximab-anti-infliximab complexes were found in non
      responders due to the presence of large amounts of HACA. This finding, supported
      by both imaging and serum analysis data, may explain failure of infliximab
      treatment.

PMID- 16793839
TI  - Increased absence due to sickness among employees with fibromyalgia.
AB  - BACKGROUND: Little is known about the effect of fibromyalgia on absence due to
      sickness in working populations. OBJECTIVE: To examine the risk of absence due to
      sickness among employees with fibromyalgia. METHODS: A prospective cohort study
      with 1-year follow-up of recorded and certified absence due to sickness after a
      survey of chronic diseases among 34 100 Finnish public sector employees (27 360
      women and 6740 men) aged 17-65 years at baseline in 2000-2. RESULTS: 20 224 days
      of absence due to sickness for the 644 employees with fibromyalgia and 454 816
      days for others were documented. Of those with fibromyalgia, 67% had co-occurring
      chronic conditions such as osteoarthritis, rheumatoid arthritis, depression or
      other psychiatric disorders. Compared with employees with none of these chronic
      conditions, the hazard ratio (HR) adjusted for age, sex and occupational status
      was 1.85-fold (95% confidence interval (CI) 1.53 to 2.18) for people with
      fibromyalgia alone and 2.63-fold (95% CI 2.34 to 2.96) for employees with
      fibromyalgia with coexisting conditions. The excess rate of absence due to
      sickness was 61 episodes/100 person-years among people with fibromyalgia alone.
      Among employees with musculoskeletal and psychiatric disorders, secondary
      fibromyalgia was associated with a 1.4-1.5-fold increase in risk of absence.
      CONCLUSION: Fibromyalgia is associated with a substantially increased risk of
      medically certified absence due to sickness that is not accounted for by
      coexisting osteoarthritis, rheumatoid arthritis or psychiatric disorders.

PMID- 16793841
TI  - Metabolic syndrome is common among middle-to-older aged Mediterranean patients
      with rheumatoid arthritis and correlates with disease activity: a retrospective,
      cross-sectional, controlled, study.
AB  - OBJECTIVES: Patients with rheumatoid arthritis have an increased risk for
      cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)-a major
      contributor to CVD-in a cohort of patients with rheumatoid arthritis and its
      relationship with rheumatoid arthritis related factors is investigated here.
      METHODS: 200 outpatients with rheumatoid arthritis (147 women and 53 men), with a
      mean (standard deviation (SD)) age of 63 (11) years, and 400 age and sex-matched
      controls were studied. MetS was assessed according to the adult treatment panel
      III criteria and rheumatoid arthritis disease activity by the disease activity
      score of 28 joints (DAS28). A standard clinical evaluation was carried out, and a
      health and lifestyle questionnaire was completed. RESULTS: The overall prevalence
      of MetS was 44% in patients with rheumatoid arthritis and 41% in controls (p =
      0.5). Patients with rheumatoid arthritis were more likely to have low high
      density lipoprotein cholesterol compared with controls (p = 0.02), whereas
      controls were more likely to have increased waist circumference or raised blood
      pressure (p = 0.001 and 0.003, respectively). In multivariate logistic regression
      analysis adjusting for demographics and rheumatoid arthritis treatment
      modalities, the risk of having moderate-to-high disease activity (DAS28>3.2) was
      significantly higher in patients with MetS compared with those with no MetS
      components (OR 9.24, 95% CI 1.49 to 57.2, p = 0.016). CONCLUSION: A high, albeit
      comparable to the control population, prevalence of MetS was found in middle-to
      older aged patients with rheumatoid arthritis. The correlation of rheumatoid
      arthritis disease activity with MetS suggests that the increased prevalence of
      coronary heart disease in patients with rheumatoid arthritis may, at least in
      part, be attributed to the inflammatory burden of the disease.

PMID- 16793842
TI  - A clinical tool to determine the necessity of spine radiography in postmenopausal
      women with osteoporosis presenting with back pain.
AB  - BACKGROUND: Vertebral fractures are underdiagnosed, although the resulting
      mortality and morbidity in postmenopausal women with osteoporosis is now
      recognised. In a population of postmenopausal women with osteoporosis and back
      pain, symptoms may be related to vertebral fractures or degenerative changes of
      the spine. AIM: To evaluate a population of postmenopausal women presenting with
      back pain and factors associated with vertebral fractures which were assessable
      in a clinical setting in order to determine the necessity for spine radiography.
      METHODS: Patient questioning and physical examination were carried out and spinal
      radiographic data collected from 410 postmenopausal women with osteoporosis, with
      an average age of 74 years, who consulted a rheumatologist for back pain. Of
      these, 215 (52.4%) patients were diagnosed with at least one vertebral fracture.
      Logistic regression was used to identify the most relevant clinical features
      associated with existing vertebral fractures, and to derive a quantitative index
      of risk. RESULTS: The model included six parameters: age, back pain intensity,
      height loss, history of low trauma non-vertebral fractures, thoracic localisation
      of back pain and sudden occurrence of back pain. The scoring system, or the
      quantitative index, had a maximal score of 16. For a score >or=7, the probability
      of existing vertebral fracture was >or=43%. The correlation between this
      quantitative index and the logistic model probability was 0.98, suggesting an
      excellent and highly significant approximation of the original prediction
      equation. CONCLUSIONS: From six clinical items, an index was built to identify
      women with osteoporosis and back pain who should have spine radiography. This
      simple tool may help clinicians to optimise vertebral fracture diagnosis and to
      make a proper therapeutic decision.

PMID- 16793843
TI  - Influence of human leucocyte antigen-DRB1 on the susceptibility to rheumatoid
      arthritis and on the production of anti-cyclic citrullinated peptide antibodies
      in a Portuguese population.
AB  - OBJECTIVE: To clarify the influence of the HLA-DRB1 locus on the susceptibility
      to rheumatoid arthritis and the production of anti-cyclic citrullinated peptide
      antibodies (anti-CCP) in a Portuguese population. METHODS: 141 patients with
      rheumatoid arthritis fulfilling the American College of Rheumatology 1987 revised
      criteria for rheumatoid arthritis were compared with 150 healthy controls. Human
      leucocyte antigen (HLA)-DRB1 locus genotyping was assessed by polymerase chain
      reaction reverse probing assays and sequence-specific primers. Anti-CCP
      antibodies were quantified by ELISA in patients with rheumatoid arthritis.
      Frequencies between groups were compared by the two-sided Fisher's exact test and
      considered significant if p<0.05. RESULTS: The HLA-DRB1*04 and HLA-DRB1*10 groups
      were highly associated with rheumatoid arthritis (p<0.001 and p = 0.031,
      respectively). High titres of anti-CCP antibodies were largely associated with
      the presence of HLA-DRB1*04/10. CONCLUSION: The well-recognised susceptibility
      alleles to rheumatoid arthritis, HLA-DRB1*04, were associated with rheumatoid
      arthritis in Portuguese patients. The relatively rare DRB1*10 was also associated
      with rheumatoid arthritis, as was described previously in other southern European
      countries. Both groups were associated with high anti-CCP titres, reinforcing its
      relevance to disease onset.

PMID- 16793844
TI  - Patterns of cardiovascular risk in rheumatoid arthritis.
AB  - BACKGROUND: Although it is known that rheumatoid arthritis is associated with an
      increased risk of cardiovascular disease (CVD), the pattern of this risk is not
      clear. This study investigated the relative risk of myocardial infarction, stroke
      and CVD mortality in adults with rheumatoid arthritis compared with adults
      without rheumatoid arthritis across age groups, sex and prior CVD event status.
      METHODS: We conducted a cohort study among all residents aged >or=18 years
      residing in British Columbia between 1999 and 2003. Residents who had visited the
      doctor at least thrice for rheumatoid arthritis (International Classification of
      Disease = 714) were considered to have rheumatoid arthritis. A non-rheumatoid
      arthritis cohort was matched to the rheumatoid arthritis cohort by age, sex and
      start of follow-up. The primary composite end point was a hospital admission for
      myocardial infarction, stroke or CVD mortality. RESULTS: 25 385 adults who had at
      least three diagnoses for rheumatoid arthritis during the study period were
      identified. During the 5-year study period, 375 patients with rheumatoid
      arthritis had a hospital admission for myocardial infarction, 363 had a
      hospitalisation for stroke, 437 died from cardiovascular causes and 1042 had one
      of these outcomes. The rate ratio for a CVD event in patients with rheumatoid
      arthritis was 1.6 (95% confidence interval (CI) 1.5 to 1.7), and the rate
      difference was 5.7 (95% CI 4.9 to 6.4) per 1000 person-years. The rate ratio
      decreased with age, from 3.3 in patients aged 18-39 years to 1.6 in those aged
      >or=75 years. However, the rate difference was 1.2 per 1000 person-years in the
      youngest age group and increased to 19.7 per 1000 person-years in those aged
      >or=75 years. Among patients with a prior CVD event, the rate ratios and rate
      differences were not increased in rheumatoid arthritis. CONCLUSIONS: This study
      confirms that rheumatoid arthritis is a risk factor for CVD events and shows that
      the rate ratio for CVD events among subjects with rheumatoid arthritis is highest
      in young adults and those without known prior CVD events. However, in absolute
      terms, the difference in event rates is highest in older adults.

PMID- 16793845
TI  - Bosentan treatment for pulmonary arterial hypertension related to connective
      tissue disease: a subgroup analysis of the pivotal clinical trials and their open
      label extensions.
AB  - BACKGROUND: Endothelin-1 is considered to be a central pathogenic factor in
      connective tissue diseases (CTDs) such as systemic sclerosis (SSc), leading to
      vasoconstriction, fibrosis, hypertrophy and inflammation. A frequent complication
      of CTD is pulmonary arterial hypertension (PAH), which has a major effect on
      functioning and quality of life, and is associated with a particularly poor
      prognosis. OBJECTIVE: To present a subgroup analysis that summarises experiences
      from the pivotal studies and their open-label extensions with the oral dual
      endothelin-1 receptor antagonist bosentan in patients with PAH and CTD, mostly
      SSc and lupus erythematosus. METHODS: 66 patients with PAH secondary to CTD, in
      World Health Organization functional class III or IV, were randomised to two
      double-blind, placebo-controlled studies and followed up for 12 and 16 weeks,
      respectively. The primary end point was change in exercise capacity, assessed
      using the 6-min walk test. In both studies and their extensions, survival was
      assessed from start of treatment to death or data cut-off and analysed as Kaplan
      Meier estimates. RESULTS: 44 patients with PAH secondary to CTD who were treated
      with bosentan were stable in 6-min walk distance at the end of the study (+19.5
      m, 95% confidence interval (CI) -3.2 to 42.2), whereas patients treated with
      placebo deteriorated (-2.6 m, 95% CI -54.0 to 48.7). 64 patients subsequently
      received bosentan in an open-label long-term extension study. Mean (standard
      deviation (SD)) exposure to bosentan was 1.6 (0.9) years, and duration of
      observation was 1.8 (0.8) years. 8 (16%) patients received epoprostenol as add-on
      treatment and 7 (14%) after discontinuation of bosentan. Survival in those
      receiving bosentan was 85.9% after 1 year and 73.4% after 2 years. CONCLUSION:
      Short-term bosentan treatment in a subgroup of patients with PAH secondary to CTD
      seems to have a favourable effect compared with placebo. The long-term follow-up
      of these patients suggests that first-line bosentan, with the subsequent addition
      of other PAH treatments if required, is safe for long-term treatment and may have
      a positive effect on outcome.

PMID- 16793846
TI  - Contemporary mortality due to acute myocardial infarction, unstable angina and
      exertional angina in a population in South East London.
AB  - BACKGROUND: Data on the contemporary mortality of coronary heart disease (CHD)
      are surprisingly sparse. AIM: To describe the contemporary mortality of all
      manifestations of CHD. DESIGN: Prospective follow-up of patients with a first
      presentation of CHD in a defined population. METHODS: We studied 537 patients
      with a first presentation of acute myocardial infarction, unstable angina or new
      exertional angina in Bromley Health Authority, London (population 295,000).
      Patients were prospectively monitored for cardiac and non-cardiac mortality for a
      median of 6 years. RESULTS: During a median 6 years follow-up, there were 88
      (16%) deaths. Survival free from cardiac death was not significantly different
      between unstable angina (92%) and new exertional angina (94%), but was lower for
      acute myocardial infarction (84%). DISCUSSION: Mortality from CHD appears to be
      falling. However, efforts to prevent myocardial infarction should continue to be
      a priority, because on-going early mortality remains high. New exertional angina
      should be diagnosed and managed promptly, as its mortality is similar to that of
      unstable angina.

PMID- 16793848
TI  - Malignant chest wall neoplasms of bone and cartilage: a pictorial review of CT
      and MR findings.
AB  - Malignant tumours of the chest wall are uncommon. The purpose of this pictorial
      essay is to describe the CT and MRI findings of malignant neoplasms affecting the
      bony skeleton of the chest wall and the costal cartilages. The most common
      primary malignant neoplasms involving the bony skeleton of the chest wall are
      chondrosarcoma, osteosarcoma and Ewing's sarcoma/primitive neuroectodermal
      tumour. Metastases, multiple myeloma and invasive primary lung cancer are the
      most frequent secondary lesions. We performed a retrospective review of the
      radiology and pathology archive at our institution from 1 July 2000 to 31
      December 2004 and identified 31 of these lesions. Several of these tumours have
      distinctive radiological features, allowing a confident radiological diagnosis to
      be suggested.

PMID- 16793847
TI  - Stomatal lock-open, a consequence of epidermal cell death, follows transient
      suppression of stomatal opening in barley attacked by Blumeria graminis.
AB  - Blumeria graminis f.sp. hordei (Bgh) attack disrupted stomatal behaviour, and
      hence leaf water conductance (g(l)), in barley genotypes Pallas and Riso-S
      (susceptible), P01 (with Mla1 conditioning a hypersensitive response; HR), and
      P22 and Riso-R (with mlo5 conditioning papilla-based penetration resistance).
      Inoculation caused some stomatal closure well before the fungus attempted
      infection. Coinciding with epidermal cell penetration, stomatal opening in light
      was also impeded, although stomata of susceptible and mlo5 lines remained largely
      able to close in darkness. Following infection, in susceptible lines stomata
      closed in darkness but opening in light was persistently impeded. In Riso-R,
      stomata recovered nearly complete function by approximately 30 h after
      inoculation, i.e. after penetration resistance was accomplished. In P01, stomata
      became locked open and unable to close in darkness shortly after epidermal cells
      died due to HR. In the P22 background, mlo5 penetration resistance was often
      followed by consequential death of attacked cells, and here too stomata became
      locked open, but not until approximately 24 h after pathogen attack had ceased.
      The influence of epidermal cell death was localized, and only affected stomata
      within one or two cells distance. These stomata were unable to close not only in
      darkness but also after application of abscisic acid and in wilted leaves
      suffering drought. Thus, resistance to Bgh based on HR or associated with cell
      death may have previously unsuspected negative consequences for the physiological
      health of apparently 'disease-free' plants. The results are discussed in relation
      to the control of stomatal aperture in barley by epidermal cells.

PMID- 16793849
TI  - Six years experience in intracoronary brachytherapy procedures: patient doses
      from fluoroscopy.
AB  - Typical patient dose levels during intracoronary brachytherapy (ICB) procedures
      using beta sources were determined across a sample of 221 treatments. Dose-area
      product values, fluoroscopy time and number of frames per procedure, with median
      values of 62 Gy cm2, 17.0 min and 1493 images, respectively, resulted in a 20% to
      50% increase in the values measured for percutaneous transluminal coronary
      angioplasty procedures in the same medical centre (median values 41 Gy cm2, 14.3
      min and 1078 images). Likely reasons for this increase include the additional
      complexity of ICB, the need for recording and reporting every step of the
      treatment, getting the essential parameters for the volume determination of the
      lesion and therapeutic radiation dose calculation and, finally, the learning
      curve for this kind of procedure. A high concentration skin dose distribution
      during ICB procedures was measured and in 12% of the patients peak skin doses
      higher than 1.5 Gy were confirmed. 10 patients were submitted to clinical follow
      up and skin injuries were not identified.

PMID- 16793850
TI  - Equivalent dose to organs and tissues in hysterosalpingography calculated with
      the FAX (Female Adult voXel) phantom.
AB  - Hysterosalpingography (HSG) is a radiological examination indicated for
      investigating infertility or uterine and tubal pathologies. Women who undergo HSG
      are relatively young, typically between 20 years and 40 years, and equivalent
      doses to the ovaries are usually reported to be around 4 mSv per examination. A
      review of studies on patient dosimetry in HSG revealed that almost all absorbed
      doses to organs and tissues had been calculated with conversion coefficients
      (CCs) based on hermaphrodite versions of MIRD5-type phantoms. The CCs applied had
      been taken from data sets for abdominal or pelvic examinations because CCs for
      HSG examination were not available. This study uses the FAX (Female Adult voXel)
      phantom in order to calculate equivalent doses to radiosensitive organs and
      tissues especially for exposure conditions used in HSG. The calculations were
      also performed for the MIRD5-type EVA phantom to demonstrate the influence of
      anatomical differences on organ equivalent dose. The results show organ and
      tissue equivalent doses as a function of the variations of the exposure
      conditions. At 4.56 mSv the ovarian equivalent dose calculated for the FAX
      phantom is about 21% greater than the average ovarian equivalent dose reported in
      the literature, which reflects the anatomical differences between the FAX and the
      MIRD5-type phantoms.

PMID- 16793851
TI  - Diffusion-weighted MRI: a new functional clinical technique for tumour imaging.

PMID- 16793852
TI  - Quantitative optical coherence tomographic elastography: method for assessing
      arterial mechanical properties.
AB  - Optical coherence tomography elastography represents a potentially attractive new
      technique for measuring elastic properties of tissues on a micron scale. In this
      study, the feasibility of optical coherence tomography (OCT) to study the
      mechanical properties of phantoms and atherosclerotic arterial samples is
      reported. The elastic modulus of tissue-mimicking phantoms was measured using OCT
      and correlated with mechanical measurements. The results indicate that
      elastography based on OCT represents an attractive technique for evaluating the
      mechanical properties of tissues.

PMID- 16793853
TI  - Physical fitness, absenteeism and workers' compensation in smoking and non
      smoking police officers.
AB  - BACKGROUND: Employers seek to minimize business costs by creating conditions of
      employment. Relying on the presumably negative effects of smoking on variables
      such as workers' compensation claims, absenteeism and physical fitness scores,
      they seek a rational basis for requirements that employees refrain from smoking.
      No research has been found on police officer smoking rates relating to physical
      fitness, and the resulting economic variables of workers' compensation claims and
      absenteeism rates. AIMS: To compare police officer non-smoker and smoker physical
      fitness, absenteeism rates and workers' compensation claims. METHODS: The sample
      included 514 officers of a metropolitan police department. A physical fitness
      test was administered. Smoking status, yearly absenteeism rates and workers'
      compensation claims were collected. RESULTS: Male smokers were significantly
      older than non-smokers. An analysis of covariance controlling for sex and age
      indicated that smokers had significantly (P < or = 0.05) lower fitness scores in
      sit and reach flexibility, sit-ups endurance, bench press strength and bicycle
      ergometer cardiovascular endurance. When neither age nor sex was controlled in
      males, a similar trend continued. However, in females only the sit and reach and
      sit-up tests demonstrated statistically significant differences. Fat percentage,
      step-test scores, absenteeism rates and workers' compensation claims were not
      statistically different. CONCLUSION: These data do not provide a rational basis
      for the requirement that officers refrain from smoking when considering body fat
      and the economic savings of lower absenteeism rates and workers' compensation. To
      some extent, smoking policies can be justified by officers' physical fitness but
      there are age, gender and test protocol considerations.

PMID- 16793854
TI  - Low back pain and occupation among Irish health service workers.
AB  - BACKGROUND: The health services sector has been identified as a high-risk work
      sector for low back pain (LBP) and related absenteeism. AIMS: To establish levels
      and predictors of LBP prevalence and associated sick leave among health service
      workers. To identify if levels of LBP or related absenteeism differ between
      occupational groups. METHODS: A postal survey using a standardized questionnaire
      and disproportionate random sampling of occupational groups was conducted at a
      single Dublin hospital. Overall hospital LBP prevalence and sickness absence were
      calculated using weighted analysis methods. Univariate analysis included the use
      of Chi-square, Fisher's exact and Mann-Whitney tests. Multivariate logistic
      regression techniques were used to explore for independent predictors of lifetime
      LBP prevalence and LBP-related sickness absence. RESULTS: An overall response
      rate of 62% (n = 246) was achieved. Lifetime, annual and point prevalence rates
      for the hospital employees were calculated at 46, 30 and 15.5%, respectively. No
      significant difference in prevalence was found between occupational groups but
      sick leave did differ with the highest level among general support and nursing
      staff. Multivariate analysis confirmed that occupation was an independent
      predictor for LBP-related sick leave (P < 0.05). CONCLUSIONS: LBP prevalence
      rates did not differ significantly between occupational groups but occupation was
      found to be an independent predictor of LBP-related sick leave. Involvement in
      manual handling did not predict either LBP or related sick leave.

PMID- 16793855
TI  - Incentives for voluntary HIV testing in NHS staff.
AB  - BACKGROUND: HIV seroprevalence is rising in the United Kingdom. While
      acceptability of HIV testing has been explored among many groups there is a
      paucity of data regarding voluntary HIV counselling and testing (VCT) among NHS
      staff. AIMS: To understand the barriers to HIV testing among NHS employees. To
      observe how these may be overcome. To assess which factors would motivate staff
      to undergo VCT and which would be a disincentive. METHODS: Completion of a cross
      sectional anonymous postal questionnaire survey of new employees at a London
      district general hospital. Demographic and attitudinal factors were collected.
      Respondents were able to give multiple responses to questions regarding reasons
      for and against VCT. Those unable to communicate in English were excluded.
      RESULTS: There was a 63% response rate; of 69 respondents, 76% were female, 72%
      had English as their first language and 30% self-identified as white British.
      Thirty-nine percent were nurses, 19% doctors and the remainder a variety of
      professions. Of these, 41% had had a previous HIV test; none were known positive.
      Sixty-two percent would consider future testing. The commonest reasons to
      consider testing were knowledge of status (79%), treatment benefit (40%) and to
      inform family members (44%). The commonest reasons not to test were already
      tested negative (30%) and rather not know (26%). CONCLUSIONS: Since the NHS is
      recruiting staff from areas of high HIV prevalence, VCT should be encouraged. NHS
      staff require information on how to access testing as well as the benefits of
      early detection of blood-borne viruses.

PMID- 16793856
TI  - Dissociating pleasantness and intensity with quinine sulfate/sucrose mixtures in
      taste.
AB  - Independent experimental manipulation of subjective intensity and hedonic tone is
      required if one wants to study their separate effects on brain activity and
      behavior. This is problematic because hedonic tone and subjective intensity are
      related, leading to a pleasantness change each time the stimulus intensity is
      altered. In the present study, a solution to this problem was explored by
      combining a pleasant-tasting substance (sucrose) and a bad-tasting substance
      (quinine sulfate) into a number of different isointense mixtures. Here we show
      that subjective intensity as well as pleasantness can be accurately predicted,
      particularly in midrange, only if one corrects for mixture suppression.

PMID- 16793857
TI  - Cross-modal interactions between olfaction and vision when grasping.
AB  - This study used kinematics to investigate the integration between vision and
      olfaction during grasping movements. Participants were requested to smell an
      odorant and then grasp an object presented in central vision. The results
      indicate that if the target was small (e.g., a strawberry), the time and
      amplitude of maximum hand aperture were later and greater, respectively, when the
      odor evoked a larger object (e.g., an orange) than when the odor evoked an object
      of a similar size as the target or no odor was presented. Conversely, the time
      and amplitude of maximum hand aperture were earlier and reduced, respectively,
      when the target was large (e.g., a peach) and the odor evoked a smaller sized
      object (e.g., an almond) than when the odor evoked an object of a similar size as
      the target or no odor was presented. Taken together, these results support the
      evidence of cross-modal links between olfaction and vision and extend this notion
      to goal-directed actions.

PMID- 16793858
TI  - Olfactory sensitivity for enantiomers and their racemic mixtures--a comparative
      study in CD-1 mice and spider monkeys.
AB  - Using a conditioning paradigm, the olfactory sensitivity of six CD-1 mice for the
      enantiomers of carvone and of limonene as well as for their racemic mixtures was
      investigated. With all six stimuli, the animals significantly discriminated
      concentrations <or=0.1 ppm (parts per million) from the odorless solvent, and
      with five of the six stimuli, the best-scoring animals were even able to detect
      concentrations <or=1 ppb (parts per billion). Five spider monkeys tested in
      parallel were found to detect the same stimuli at concentrations <1 ppm, and with
      two of the stimuli, they were also able to discriminate concentrations <1 ppb
      from the solvent. The results showed 1) both CD-1 mice and spider monkeys to have
      a well-developed olfactory sensitivity for the stimuli tested, with no systematic
      difference in performance between species; 2) the effect of chirality on
      detectability of the enantiomers to be substance specific; 3) no systematic
      effect of the presence (carvone) or absence (limonene) of a functional carbonyl
      group on detectability of the enantiomers; and 4) that spider monkeys detected
      the racemic mixtures of both carvone and limonene at lower concentrations
      compared to the unmixed compounds, whereas the mice failed to do so. These
      findings lend support to the growing body of evidence suggesting that between
      species comparisons of the relative size of olfactory brain structures do not
      allow us to reliably predict olfactory sensitivity. As mice and spider monkeys
      are thought to share a similar number of functional olfactory receptor genes, the
      findings further suggest that differences in the relative abundance of chiral
      specific olfactory receptor types might account for the observed difference in
      mixture additivity at threshold level between the two species. These threshold
      data may provide useful information for the choice of adequate stimulus
      concentrations in electrophysiological or imaging studies of the olfactory system
      or investigations of the discriminative abilities of mice and spider monkeys.

PMID- 16793859
TI  - Apolipoprotein E4 and traumatic brain injury.

PMID- 16793860
TI  - Cord atrophy separates early primary progressive and relapsing remitting multiple
      sclerosis.
AB  - BACKGROUND AND OBJECTIVE: The onset of multiple sclerosis is relapsing remitting
      or primary progressive. An improved understanding of the causes of early
      progressive disability in primary progressive multiple sclerosis (PPMS) could
      provide mechanistic targets for therapeutic intervention. METHODS: Five magnetic
      resonance imaging (MRI) parameters that could potentially cause progressive
      disability were investigated in 43 patients with early PPMS and in 37 patients
      with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both
      grey matter and white matter; intrinsic abnormality in brain, both grey matter
      and white matter (measured by the magnetisation transfer ratio (MTR)); and
      atrophy of the upper cervical spinal cord. Both groups were also compared with
      controls. RESULTS: Patients with PPMS were older and more likely to be men. Both
      patient groups had atrophy of brain grey matter and white matter, and intrinsic
      abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy
      was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2;
      controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of
      all five MRI parameters, age and sex. CONCLUSION: Grey matter and white matter of
      the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present
      only in PPMS. This is concordant with myelopathy being the usual clinical
      presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant
      in PPMS treatment trials.

PMID- 16793861
TI  - Invited commentary: ripeness is all.

PMID- 16793862
TI  - A case-crossover study of fine particulate matter air pollution and onset of
      congestive heart failure symptom exacerbation leading to hospitalization.
AB  - Persons with congestive heart failure may be susceptible to ambient air
      pollution. The authors evaluated the association between exposure to particulate
      matter with an aerodynamic diameter of <2.5 microm (PM2.5) and onset of symptom
      exacerbation leading to hospital admission in Baltimore, Maryland. They used a
      case-crossover design for 135 case events occurring among 125 persons with
      prevalent congestive heart failure who were admitted to a single hospital through
      the emergency department during 2002. The case period was assigned using three
      index times: 8-hour and 24-hour periods of symptom onset and date of hospital
      admission. Controlling for weather, the authors detected a modest relative
      increase in risk for cases defined by 8-hour symptom onset for an interquartile
      range increase in PM2.5 at a 2-day lag (odds ratio=1.09, 95% confidence interval:
      0.91, 1.30). A corresponding increase in risk was not observed when admission
      date was used to define the case period. A series of simulations based on study
      data indicated that the study had adequate statistical power to detect odds
      ratios of 1.2 or higher. Although overall findings were not statistically
      significant, the identification of case events defined by an 8-hour onset period
      may be more relevant than either a 24-hour onset period or the admission date for
      estimating harmful effects of air pollutant exposure on cardiovascular health.

PMID- 16793863
TI  - Pennisetum squamulatum: is the predominant cytotype hexaploid or octaploid?
AB  - Apomixis is a mode of asexual reproduction where maternal clones are produced
      through seeds. Consequently, genetic segregation is prevented in hybrid
      progenies. Pennisetum squamulatum has been used to transfer apomixis into the
      related sexual species Pennisetum glaucum by the introgression of an apospory
      specific genomic region (ASGR)-carrier chromosome. Crosses between P. glaucum and
      P. squamulatum or Pennisetum purpureum have been relatively easy to make even
      though P. squamulatum has been reported to have a different basic chromosome
      number than the other 2 species (9 vs. 7) and to be hexaploid (2n = 6x = 54). Our
      extensive examination of one accession had shown a chromosome number of 2n = 56.
      In order to determine if there was a variation among accessions, we counted the
      number of chromosomes in 5 accessions of P. squamulatum using centromeric and 18S
      5.8S-26S rDNA probes as molecular cytological markers. Our results showed that P.
      squamulatum is most likely octaploid with a basic chromosome number of 7 (2n = 8x
      = 56) and may belong to the secondary gene pool of Pennisetum. Moreover, a
      morphologically similar ASGR-carrier chromosome that confers apomixis was
      observed in all accessions.

PMID- 16793865
TI  - Genetic characterization of Argentine and Bolivian Creole cattle breeds assessed
      through microsatellites.
AB  - In the present report, the polymorphisms from 9 microsatellites were used to
      assess genetic diversity and relationships in 4 Creole cattle breeds from
      Argentina and Bolivia, 4 European taurine breeds, and 2 American zebu
      populations. The Creole populations display a relatively high level of genetic
      variation as estimated by allelic diversity and heterozygosity, whereas the
      British breeds displayed reduced levels of genetic diversity. The analysis of
      molecular variance indicated that 7.8% of variance can be explained by
      differences among taurine and zebu breeds. Consistent with these results, the
      first principal component (PC), which comprised the 40% of the total variance,
      clearly distinguishes these 2 groups. In addition, all constructed phylogenetic
      trees cluster together Nelore and Brahman breeds with robust bootstrap values.
      Only 1% of variance was due to difference between American Creole and European
      taurine cattle. Although this secondary split was supported by the classical
      genetic distance and the second PC (15%), the topology of trees is not
      particularly robust. The presence of zebu-specific alleles in Creole cattle
      allowed estimating a moderate degree of zebu admixture. When these data were
      compared with mitochondrial and Y chromosomal studies, a clear pattern of male
      mediated introgression was revealed. The results presented here contribute to the
      understanding of origin and history of the American Creole cattle.

PMID- 16793864
TI  - A quantitative trait locus analysis of natural genetic variation for Drosophila
      melanogaster oxidative stress survival.
AB  - Little is known about natural genetic variation for survival under oxidative
      stress conditions or whether genetic variation for oxidative stress survival is
      associated with that for life-history traits. We have investigated survival in a
      high-oxygen environment at 2 adult densities using a set of recombinant inbred
      lines (RILs) isolated from a natural population of Drosophila melanogaster.
      Female and male oxidative stress survival was highly correlated. Quantitative
      trait loci (QTLs) for oxidative stress survival were identified on both
      autosomes. These QTLs were sometimes sex or density specific but were most often
      not. QTLs were identified that colocalize to the same region of the genome as
      longevity in other studies using the same set of RILs. We also determined early
      age egg production and found QTLs for this trait, but there was no support for an
      association between oxidative stress survival and egg production.

PMID- 16793866
TI  - Population differentiation and the effects of herbivory and sand compaction on
      the subterranean growth of a desert lily.
AB  - Differences in level of herbivory can select for local adaptation and genetic
      differentiation of plant populations in different environments. Mean bulb depth
      of the desert lily Pancratium sickenbergeri, differs considerably among
      populations differing in the level of herbivory by the dorcas gazelle. The
      gazelle digs in the sand to remove most of the bulb of the lily. Deeper bulbs
      have less material removed by herbivory than shallow bulbs and have higher
      fitness. A possible confounding factor is the degree of sand compaction, which
      may retard the downward growth of the bulb. We conducted a common garden
      experiment with 2 sand types with seeds from source populations with different
      levels of herbivory. There was a large genetic difference among populations. Two
      of 3 analyses indicated that there was an interaction between population and sand
      type, indicating that there is a heritable component of plasticity.

PMID- 16793868
TI  - Access point analysis: what do adolescents in South Africa say about tobacco
      control programmes?
AB  - This paper explores adolescent preferences for the setting, timing, delivery
      format, provider and key elements of tobacco control programmes. The need for
      programme sensitivity towards urban/rural, gender and ethnic subgroups is also
      discussed. Schools were purposively selected from the Southern Cape-Karoo Region,
      South Africa. Twelve prevention and nine cessation focus group discussions were
      conducted with Grade 6-8 students and Grade 8-9 smokers and ex-smokers,
      respectively. Adolescents reported similar preferences for prevention and
      cessation programmes. Although they were unaware of smoking prevention or
      cessation programmes, they reported a willingness to participate in such
      programmes. Programmes should include school-based activities that are supported
      by out-of-school activities held over weekends and holidays. Non-judgemental and
      empathetic teachers and peers, as well as ex-smokers were preferred as programme
      providers. School-based participatory delivery formats should be supported by
      community-based mass media approaches. Programmes can be jointly presented to
      boys and girls of diverse ethnic backgrounds with some gender-sensitive sessions.
      Programme participation and sustainability would be enhanced if it were exciting,
      fun filled and integrated into their daily lives. School-based programmes must be
      embedded within comprehensive approaches that involve community- and policy-level
      interventions.

PMID- 16793869
TI  - Human skin responses to UV radiation: pigment in the upper epidermis protects
      against DNA damage in the lower epidermis and facilitates apoptosis.
AB  - Melanin plays an important role in protecting the skin against UV radiation, and
      melanomas and basal/squamous cell carcinomas occur more frequently in individuals
      with fair/light skin. We previously reported that levels of melanin correlate
      inversely with amounts of DNA damage induced by UV in normal human skin of
      different racial/ethnic groups. We have now separately examined DNA damage in the
      upper and lower epidermal layers in various types of skin before and after
      exposure to UV and have measured subsequent apoptosis and phosphorylation of p53.
      The results show that two major mechanisms underlie the increased
      photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower
      epidermis (including keratinocyte stem cells and melanocytes) is more effectively
      prevented in darker skin, suggesting that the pigmented epidermis is an efficient
      UV filter. Second, UV-induced apoptosis is significantly greater in darker skin,
      which suggests that UV-damaged cells may be removed more efficiently in pigmented
      epidermis. The combination of decreased DNA damage and more efficient removal of
      UV-damaged cells may play a critical role in the decreased photocarcinogenesis
      seen in individuals with darker skin.

PMID- 16793870
TI  - Constitutive and UV-induced metabolism of melatonin in keratinocytes and cell
      free systems.
AB  - Melatonin, which can be produced in the skin, exerts a protective effect against
      damage induced by UV radiation (UVR). We have investigated the effect of UVB, the
      most damaging component of UVR, on melatonin metabolism in HaCaT keratinocytes
      and in a cell-free system. Four metabolites were identified by HPLC and LC-MS: 6
      hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), 2
      hydroxymelatonin (the main intermediate between melatonin and AFMK), and 4
      hydroxymelatonin. Concentrations of these photoproducts were directly
      proportional to UVR-dose and to melatonin substrate content, and their
      accumulation was time-dependent. The UVR-dependent increase of AFMK and 2
      hydroxymelatonin was also detected in keratinocytes, where it was accompanied by
      simultaneous consumption of intracellular melatonin. Of note, melatonin and its
      two major metabolites, 2-hydroxymelatonin and AFMK, were also detected in
      untreated keratinocytes, neither irradiated nor preincubated with melatonin.
      Thus, intracellular melatonin metabolism is enhanced under exposure to UVR. The
      additional biological activity of these individual melatonin metabolites
      increases the spectrum of potential actions of the recently identified cutaneous
      melatoninergic system.

PMID- 16793871
TI  - Activation of the stress protein response prevents the development of pulmonary
      edema by inhibiting VEGF cell signaling in a model of lung ischemia-reperfusion
      injury in rats.
AB  - Lung endothelial damage is a characteristic morphological feature of ischemia
      reperfusion (I/R) injury, although the molecular steps involved in the loss of
      endothelial integrity are still poorly understood. We tested the hypothesis that
      the activation of vascular endothelial growth factor (VEGF) cell signaling would
      be responsible for the increase in lung vascular permeability seen early after
      the onset of I/R in rats. Furthermore, we hypothesized that the I/R-induced
      pulmonary edema would be significantly attenuated in rats by the activation of
      the stress protein response. Pretreatment with Ad Flk-1, an adenovirus encoding
      for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung
      vascular permeability in rats. Furthermore, the I/R-induced lung injury was
      significantly decreased by prior activation of the stress protein response with
      geldanamycin or pyrrolidine dithiocarbamate. In vitro studies demonstrated that
      VEGF caused an increase in protein permeability across primary cultures of bovine
      macro- and microvascular lung endothelial cell monolayers that were associated
      with a phosphorylation of VE- and E-cadherin and the formation of actin stress
      fibers. Activation of the stress protein response prevented the VEGF-mediated
      changes in protein permeability across these cell monolayers and reduced the
      phosphorylation of VE-and E-cadherins, as well as the formation of actin stress
      fibers in these cells.

PMID- 16793872
TI  - Reversal of mitochondrial defects before ischemia protects the aged heart.
AB  - Myocardial injury is increased in the aged heart during ischemia and reperfusion.
      Aging decreases oxidative metabolism in interfibrillar mitochondria (IFM) located
      between the myofibrils. We asked whether reversal of aging defects in IFM before
      ischemia would decrease injury in the aged heart following ischemia and
      reperfusion. Treatment with acetylcarnitine (AcCN) increases the activity of
      cytochrome oxidase in the aged heart. Aged (24 months) and adult (6 months)
      Fischer 344 rats were treated with AcCN (300 mg/kg i.p. 3 h before excision of
      the heart) or served as controls. AcCN restored oxidative phosphorylation and the
      activity of complexes III and IV in IFM from aged hearts to rates present in
      adults. Isolated hearts underwent 25 min global ischemia and 30 min reperfusion
      without additional treatment. Contractile recovery during reperfusion improved in
      hearts from AcCN-treated aged rats compared to aged controls and were similar to
      adults in recovery. AcCN-treated aged hearts sustained less damage, indicated by
      decreased lactate dehydrogenase (LDH) release during reperfusion. AcCN treatment
      did not alter functional recovery or LDH release in adults. Restoration of
      mitochondrial function in the aged heart before ischemia was accompanied by
      enhanced contractile recovery and decreased tissue injury following ischemia and
      reperfusion.

PMID- 16793873
TI  - Stem cell research: the California experience.

PMID- 16793874
TI  - Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion.
AB  - Deletion of synaptobrevin/vesicle-associated membrane protein, the major synaptic
      vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R
      SNARE), severely decreases but does not abolish spontaneous and evoked synaptic
      vesicle exocytosis. We now show that the closely related R-SNARE protein
      cellubrevin rescues synaptic transmission in synaptobrevin-deficient neurons but
      that deletion of both cellubrevin and synaptobrevin does not cause a more severe
      decrease in exocytosis than deletion of synaptobrevin alone. We then examined the
      structural requirements for synaptobrevin to function in exocytosis. We found
      that substituting glutamine for arginine in the zero-layer of the SNARE motif did
      not significantly impair synaptobrevin-dependent exocytosis, whereas insertion of
      12 or 24 residues between the SNARE motif and transmembrane region abolished the
      ability of synaptobrevin to mediate Ca2+-evoked exocytosis. Surprisingly,
      however, synaptobrevin with the 12-residue but not the 24-residue insertion
      restored spontaneous release in synaptobrevin-deficient neurons. Our data suggest
      that synaptobrevin mediates Ca2+-triggered exocytosis by tight coupling of the
      SNARE motif to the transmembrane region and hence forcing the membranes into
      close proximity for fusion. Furthermore, the fusion reactions underlying evoked
      and spontaneous release differ mechanistically.

PMID- 16793875
TI  - Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes.
AB  - The interplay between fear expression and fear extinction provides an important
      prerequisite for adequate coping with aversive encounters. Current models propose
      that extinction of conditioned fear is mediated by associative safety learning.
      Here, we demonstrate that the cannabinoid CB1 receptor, which is crucially
      involved in fear extinction, is dispensable for associative safety learning. In
      fact, our results indicate that CB1 mediates fear extinction primarily via
      habituation-like processes. CB1 null-mutant mice were severely impaired not only
      in extinction of the fear response to a tone after fear conditioning but also in
      habituation of the fear response to a tone after sensitization with an
      inescapable footshock. Surprisingly, long-term habituation was generally affected
      even in situations with proper short-term adaptation, suggesting the existence of
      two separated CB1-dependent effector systems for short- and long-term fear
      adaptation. Our findings underscore the importance of habituation as a
      determinant of fear extinction in mice and characterize the cannabinoid CB1
      receptor as an essential molecular correlate of this process.

PMID- 16793876
TI  - Kiss1 neurons in the forebrain as central processors for generating the
      preovulatory luteinizing hormone surge.
AB  - Kisspeptins are neuropeptides encoded by the Kiss1 gene, which have been
      implicated in the neuroendocrine regulation of gonadotropin-releasing hormone
      (GnRH) secretion. The goal of this study was to test the hypothesis that
      activation of Kiss1 neurons in the anteroventral periventricular nucleus (AVPV)
      is linked to the induction of the preovulatory luteinizing hormone (LH) surge in
      the rat. First, we determined that levels of Kiss1 mRNA in the AVPV peaked during
      the evening of proestrus, whereas Kiss1 mRNA in the arcuate nucleus (Arc) was at
      its nadir. Second, we corroborated this observation by demonstrating that Kiss1
      mRNA is increased in the AVPV at the time of an estrogen (E)- and progesterone
      induced LH surge in ovariectomized animals, whereas in the Arc, the expression of
      Kiss1 mRNA was decreased. Third, we found that most Kiss1 neurons in the AVPV
      coexpress the immediate early gene Fos coincidently with the LH surge, but
      virtually none coexpressed Fos on diestrus. In contrast, Kiss1 neurons in the Arc
      were Fos negative at the time of the LH surge as well as on diestrus. Finally, we
      found that most Kiss1 neurons in the AVPV and Arc express estrogen receptor alpha
      mRNA, suggesting that E acts directly on these neurons. These results suggest
      that Kiss1 neurons in the AVPV play an active role in mediating the effects of E
      on the generation of the preovulatory GnRH/LH surge on proestrus.

PMID- 16793877
TI  - Comparison of reward modulation in the frontal eye field and caudate of the
      macaque.
AB  - The frontal eye field (FEF) influences saccade generation via direct projections
      to the superior colliculus and an indirect pathway through the basal ganglia. To
      test whether different reward information is represented in the FEF and the basal
      ganglia, we recorded from the FEF and the caudate nucleus in monkeys performing
      an asymmetrically rewarded memory-guided saccade task. A peripheral cue at one of
      two opposing positions was flashed briefly to indicate the saccade target. In a
      given block, one position was associated with big reward and the other with small
      reward. Big-reward position was alternated between blocks. In this task, the FEF
      and caudate displayed similar prevalence of neuronal activity before cue onset
      that was larger in blocks with specific big reward-cue position associations.
      They also exhibit comparable reward modulation of visual responses that were
      spatially selective. In contrast, visual responses that were specific to expected
      reward size, instead of spatial locations, were commonly observed in caudate but
      rarely seen in the FEF. Thus, both the FEF and basal ganglia may contribute to
      reward bias in saccade generation, with the FEF providing spatially relevant
      reward information and the basal ganglia providing additional reward-specific
      information.

PMID- 16793878
TI  - The properties and implications of NMDA spikes in neocortical pyramidal cells.
AB  - Integration of synaptic input in dendritic trees is a nonlinear process in which
      excitatory input may elicit spikes localized within the branch receiving input.
      In addition to membrane current-driven events, a type of dendritic spike has
      recently been described that instead depends on NMDA receptor current. These NMDA
      spikes enable superlinear integration among inputs targeted close together on a
      single branch. Here a compartment model of a layer 5 pyramidal cell was used to
      examine the mechanisms underlying NMDA spikes and to test properties not directly
      accessible experimentally. The results indicate the following: initiation of an
      NMDA spike in a tertiary dendrite in 1 mm [Mg2+] requires an NMDA conductance
      density equivalent to 6-8 nS within a 25-microm-long dendritic subsegment;
      dendritic membrane currents are not required for NMDA spike production; and
      targeted dendritic (but not somatic) inhibitory input is exquisitely suited to
      veto an NMDA spike if it arrives within a 30 ms window in time. Finally, an
      analysis of the spatial density of NMDA conductance required for NMDA spike
      production implies that, at least up to the age (postnatal day 35) that these
      events have been observed, most of the excitatory synaptic conductance arriving
      at pyramidal cells is NMDA mediated.

PMID- 16793879
TI  - Impaired nociception and inflammatory pain sensation in mice lacking the
      prokineticin receptor PKR1: focus on interaction between PKR1 and the capsaicin
      receptor TRPV1 in pain behavior.
AB  - Bv8, prokineticin-1 or EG-VEGF (endocrine gland-derived vascular endothelial
      growth factor), and prokineticin-2, are naturally occurring peptide agonists of
      two G-protein-coupled receptors (GPCRs), prokineticin receptor 1 (PKR1) and PKR2.
      PKRs are expressed in neurons in the CNS and peripheral nervous system and many
      dorsal root ganglion (DRG) cells expressing PKRs also express transient receptor
      potential vanilloid receptor-1 (TRPV1). Mice lacking the pkr1 gene were generated
      to explore the role of the PKR1 receptor in nociceptive signaling and in
      nociceptor sensitization. When compared with wild-type littermates, mice lacking
      the pkr1 gene showed impaired responsiveness to noxious heat, mechanical stimuli,
      capsaicin, and protons. In wild-type mice, activation of PKRs by the PKR agonist
      Bv8 caused hyperalgesia and sensitized to the actions of capsaicin. pkr1-null
      mice exhibited impaired responses to Bv8 but showed normal hyperalgesic responses
      to bradykinin and PGE2 (prostaglandin E2). Conversely, trpv1-null mice showed a
      reduced pronociceptive response to Bv8. Additionally, pkr1-null mice showed
      diminished thermal hyperalgesia after acute inflammation elicited by mustard oil
      and reduced pain behavior after chronic inflammation produced by complete
      Freund's adjuvant. The number of neurons that responded with a [Ca2+]i increase
      to Bv8 exposure was five times lower in pkr1-null DRG cultures than in wild-type
      cultures. Furthermore, Bv8-responsive neurons from pkr1-null mice showed a
      significant reduction in the [Ca2+]i response to capsaicin. These findings
      indicate a modulatory role of PKR1 in acute nociception and inflammatory pain and
      disclose a pharmacological interaction between PKR1 and TRPV1 in nociceptor
      activation and sensitization.

PMID- 16793880
TI  - Retinal waves trigger spindle bursts in the neonatal rat visual cortex.
AB  - During visual system development, the light-insensitive retina spontaneously
      generates waves of activity, which are transmitted to the lateral geniculate
      nucleus. The crucial question is whether retinal waves are further transmitted to
      the cortex and influence the early cortical patterns of activity. Using
      simultaneous recordings from the rat retina and visual cortex during the first
      postnatal week in vivo, we found that spontaneous retinal bursts are correlated
      with spindle bursts (intermittent network bursts associated with spindle-shape
      field oscillations) in the contralateral visual cortex (V1). V1 spindle bursts
      could be evoked by electrical stimulation of the optic nerve. Intraocular
      injection of forskolin, which augments retinal waves, increased the occurrence of
      V1 spindle bursts. Blocking propagation of retinal activity, or removal of the
      retina reduced the frequency, but did not completely eliminate the cortical
      spindle bursts. These results indicate that spontaneous retinal waves are
      transmitted to the visual cortex and trigger endogenous spindle bursts. We
      propose that the interaction between retinal waves and spindle bursts contributes
      to the development of visual pathways to the cortex.

PMID- 16793882
TI  - Vasotocin and mesotocin stimulate the biosynthesis of neurosteroids in the frog
      brain.
AB  - The neurohypophysial nonapeptides vasopressin (VP) and oxytocin (OT) modulate a
      broad range of cognitive and social activities. Notably, in amphibians, vasotocin
      (VT), the ortholog of mammalian VP, plays a crucial role in the control of sexual
      behaviors. Because several neurosteroids also regulate reproduction-related
      behaviors, we investigated the possible effect of VT and the OT ortholog
      mesotocin (MT) in the control of neurosteroid production. Double
      immunohistochemical labeling of frog brain sections revealed the presence of
      VT/MT-positive fibers in close proximity of neurons expressing the steroidogenic
      enzymes 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3beta-HSD)
      and cytochrome P450 17alpha-hydroxylase/c17, 20-lyase (P450(C17)). High
      concentrations of VT and MT receptor mRNAs were observed in diencephalic nuclei
      containing the 3beta-HSD and P450(C17) neuronal populations. Exposure of frog
      hypothalamic explants to graded concentrations of VT or MT produced a dose
      dependent increase in the formation of progesterone, 17-hydroxypregnenolone, 17
      hydroxyprogesterone, and dehydroepiandrosterone. The stimulatory effect of VT and
      MT on neurosteroid biosynthesis was mimicked by VP and OT, as well as by a
      selective V1b receptor agonist, whereas V2 and OT receptor agonists had no
      effect. VT-induced neurosteroid production was completely suppressed by selective
      V1a receptor antagonists and was not affected by V2 and OT receptor antagonists.
      Concurrently, the effect of MT on neurosteroidogenesis was markedly attenuated by
      selective OT and V1a receptor antagonists but not by a V2 antagonist. The present
      study provides the first evidence for a regulatory effect of VT and MT on
      neurosteroid biosynthesis. These data suggest that neurosteroids may mediate some
      of the behavioral actions of VT and MT.

PMID- 16793881
TI  - Dual circuitry for odor-shock conditioning during infancy: corticosterone
      switches between fear and attraction via amygdala.
AB  - Rat pups must learn maternal odor to support attachment behaviors, including
      nursing and orientation toward the mother. Neonates have a sensitive period for
      rapid, robust odor learning characterized by increased ability to learn odor
      preferences and decreased ability to learn odor aversions. Specifically, odor-0.5
      mA shock association paradoxically causes an odor preference and coincident
      failure of amygdala activation in pups until postnatal day 10 (P10). Because
      sensitive-period termination coincides with a declining "stress hyporesponsive
      period" when corticosterone release is attenuated, we explored the role of
      corticosterone in sensitive-period termination. Odor was paired with 0.5 mA shock
      in either sensitive-period (P8) or postsensitive-period (P12) pups while
      manipulating corticosterone. We then assessed preference/aversion learning and
      the olfactory neural circuitry underlying its acquisition. Although sensitive
      period control paired odor-shock pups learned an odor preference without amygdala
      participation, systemic (3 mg/kg, i.p.; 24 h and 30 min before training) or intra
      amygdala corticosterone (50 or 100 ng; during training) permitted precocious odor
      aversion learning and evoked amygdala neural activity similar to that expressed
      by older pups. In postsensitive-period (P12) pups, control paired odor-shock pups
      showed an odor aversion and amygdala activation, whereas corticosterone-depleted
      (adrenalectomized) paired odor-shock pups showed odor-preference learning and
      activation of an odor learning circuit characteristic of the sensitive period.
      Intra-amygdala corticosterone receptor antagonist (0.3 ng; during training)
      infused into postsensitive-period (P12) paired odor-shock pups also showed odor
      preference learning. These results suggest corticosterone is important in
      sensitive-period termination and developmental emergence of olfactory fear
      conditioning, acting via the amygdala as a switch between fear and attraction.
      Because maternal stimulation of pups modulates the pups' endogenous
      corticosterone, this suggests maternal care quality may alter sensitive-period
      duration.

PMID- 16793883
TI  - Reward association affects neuronal responses to visual stimuli in macaque te and
      perirhinal cortices.
AB  - To study the roles of the perirhinal cortex (PRh) and temporal cortex (area TE)
      in stimulus-reward associations, we recorded spike activities of cells from PRh
      and TE in two monkeys performing a visually cued go/no-go task. Each visual cue
      indicated the required motor action as well as the availability of reward after
      correct completion of the trial. Eighty object images were divided into four
      groups, each of which was assigned to one of four motor-reward conditions. The
      monkeys either had to release a lever (go response) or keep pressing it (no-go
      response), depending on the cue. Each of the go and no-go trials could be either
      a rewarded or unrewarded trial. A liquid reward was provided after correct
      responses in rewarded trials, whereas correct responses were acknowledged only by
      audiovisual feedback in unrewarded trials. Several measures of the monkeys'
      behavior indicated that the monkeys correctly anticipated the reward availability
      in each trial. The dependence of neuronal activity on the reward condition was
      examined by comparing mean discharges to each of the 40 rewarded stimuli with
      those to each of the 40 unrewarded stimuli. Many cells in both areas showed
      significant reward dependence in their responses to the visual cues, and this was
      not likely attributable to differences in behavior across conditions because the
      variations in neuronal activity were not correlated with trial-by-trial
      variations in latency of go responses or anticipatory sucking strength. These
      results suggest the involvement of PRh and TE in associating visual stimuli with
      reward outcomes.

PMID- 16793884
TI  - Axonal transport of human immunodeficiency virus type 1 envelope protein
      glycoprotein 120 is found in association with neuronal apoptosis.
AB  - Patients infected by human immunodeficiency virus type 1 (HIV-1) develop acquired
      immune deficiency syndrome-associated dementia complex (ADC), a disorder
      characterized by a broad spectrum of motor impairments and cognitive deficits.
      The number of cells in the brain that are productively infected by HIV-1 is
      relatively small and consists predominantly of macrophages and microglia, yet HIV
      1 causes widespread neuronal loss. A better understanding of the pathogenic
      mechanisms mediating HIV-1 neurotoxicity is crucial for developing effective
      neuroprotective therapies against ADC. The HIV-1 envelope glycoprotein 120
      (gp120), which is shed from the virus, is one of the agents causing neuronal cell
      death. However, the cellular mechanisms underlying its neurotoxic effect remain
      unclear. We report that gp120 injected into the rat striatum or hippocampus is
      sequestered by neurons and subsequently retrogradely transported to distal
      neurons that project to these brain areas. Cleaved caspase-3 and terminal
      deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling,
      hallmarks of apoptosis, were seen in neurons internalizing and transporting
      gp120. The retrograde transport of gp120 and apoptosis were mediated by the
      chemokine receptor CXCR4 because AMD3100, a selective CXCR4 inhibitor, blocked
      both events. Furthermore, colchicine or nocodazole, two inhibitors of
      intracellular trafficking, abolished gp120-mediated apoptosis in distal areas.
      These results indicate that axonal transport of gp120 might play a role in HIV-1
      mediated widespread neuronal cell death.

PMID- 16793885
TI  - Glial progenitors in adult white matter are driven to form malignant gliomas by
      platelet-derived growth factor-expressing retroviruses.
AB  - To test the gliomagenic potential of adult glial progenitors, we infected adult
      rat white matter with a retrovirus that expresses high levels of PDGF and green
      fluorescent protein (GFP). Tumors that closely resembled human glioblastomas
      formed in 100% of the animals by 14 d postinfection. Surprisingly, the tumors
      were composed of a heterogeneous population of cells, <20% of which expressed the
      retroviral reporter gene (GFP). The vast majority of both GFP+ and GFP- tumor
      cells expressed markers of glial progenitors. Thus, the tumors arose from the
      massive expansion of both infected and uninfected glial progenitors, suggesting
      that PDGF was driving tumor formation via autocrine and paracrine stimulation of
      glial progenitor cells. To explore this possibility further, we coinjected a
      retrovirus expressing PDGF-IRES-DsRed with a control retrovirus expressing only
      GFP. The resulting tumors contained a mixture of red cells (PDGF-expressing/tumor
      initiating cells) and green cells (recruited progenitors). Both populations were
      highly proliferative and infiltrative. In contrast, when the control GFP
      retrovirus was injected alone, the animals never formed tumors and the majority
      of infected cells differentiated along the oligodendrocyte lineage. Together,
      these results reveal that adult white matter progenitors not only have the
      capacity to give rise to gliomas, but resident progenitors are recruited to
      proliferate within the mitogenic environment of the tumor and in this way
      contribute significantly to the heterogeneous mass of cells that compose a
      malignant glioma.

PMID- 16793886
TI  - Linking neural representation to function in stereoscopic depth perception: roles
      of the middle temporal area in coarse versus fine disparity discrimination.
AB  - Neurons selective for binocular disparity form the neural substrate for
      stereoscopic depth perception and are found in several areas of primate visual
      cortex. Presumably, multiple representations of disparity exist to serve
      different functions, but the specific contributions of different visual areas to
      depth perception remain poorly understood. We examine this issue by comparing the
      contributions of the middle temporal (MT) area to performance of two depth
      discrimination tasks: a "coarse" task that involves discrimination between
      absolute disparities in the presence of noise, and a "fine" task that involves
      discrimination of very small differences in relative disparity between two
      stimuli in the absence of noise. In the fine task, we find that electrical
      microstimulation of MT does not affect perceptual decisions, although many
      individual MT neurons have sufficient sensitivity to account for behavioral
      performance. In contrast, microstimulation at the same recording sites does bias
      depth percepts in the coarse task. We hypothesized that these results may be
      explained by the fact that MT neurons do not represent relative disparity signals
      that are thought to be essential for the fine task. This hypothesis was supported
      by single-unit recordings that show that MT neurons signal absolute, but not
      relative, disparities in a stimulus configuration similar to that used in the
      fine task. This work establishes a link between the neural representation of
      disparity in MT and the functional contributions of this area to depth
      perception.

PMID- 16793887
TI  - Vascular endothelial growth factor directly inhibits primitive neural stem cell
      survival but promotes definitive neural stem cell survival.
AB  - There are two types of neural stem cells (NSCs). Primitive NSCs [leukemia
      inhibitory factor (LIF) dependent but exogenous fibroblast growth factor (FGF) 2
      independent] can be derived from mouse embryonic stem (ES) cells in vitro and
      from embryonic day 5.5 (E5.5) to E7.5 epiblast and E7.5-E8.5 neuroectoderm in
      vivo. Definitive NSCs (LIF independent but FGF2 dependent) first appear in the
      E8.5 neural plate and persist throughout life. Primitive NSCs give rise to
      definitive NSCs. Loss and gain of functions were used to study the role of
      vascular endothelial growth factor (VEGF)-A and its receptor, Flk1, in NSCs. The
      numbers of Flk1 knock-out mice embryo-derived and ES cell-derived primitive NSCs
      were increased because of the enhanced survival of primitive NSCs. In contrast,
      neural precursor-specific, Flk1 conditional knock-out mice-derived, definitive
      NSCs numbers were decreased because of the enhanced cell death of definitive
      NSCs. These effects were not observed in cells lacking Flt1, another VEGF
      receptor. In addition, the cell death stimulated by VEGF-A of primitive NSC and
      the cell survival stimulated by VEGF-A of definitive NSC were blocked by Flk1/Fc
      soluble receptors and VEGF-A function-blocking antibodies. These VEGF-A
      phenotypes also were blocked by inhibition of the downstream effector nuclear
      factor kappaB (NF-kappaB). Thus, both the cell death of primitive NSC and the
      cell survival of definitive NSC induced by VEGF-A stimulation are mediated by
      bifunctional NF-kappaB effects. In conclusion, VEGF-A function through Flk1
      mediates survival (and not proliferative or fate change) effects on NSCs,
      specifically.

PMID- 16793888
TI  - Chronic valproic acid treatment triggers increased neuropeptide y expression and
      signaling in rat nucleus reticularis thalami.
AB  - Valproate (VPA) can suppress absence and other seizures, but its precise
      mechanisms of action are not completely understood. We investigated whether VPA
      influences the expression of neuropeptide Y (NPY), an endogenous anticonvulsant.
      Chronic VPA administration to young rats (300-600 mg.kg(-1).d(-1) in divided
      doses over 4 d) resulted in a 30-50% increase in NPY mRNA and protein expression
      in the nucleus reticularis thalami (nRt) and hippocampus, but not in the
      neocortex, as shown by real-time PCR, radioimmunoassay, and immunohistochemistry.
      No increased expression was observed after a single acute dose of VPA. Chronic
      treatment with the pharmacologically inactive VPA analog octanoic acid did not
      elicit changes in NPY expression. No significant expression changes could be
      shown for the mRNAs of the Y1 receptor or of the neuropeptides somatostatin,
      vasoactive intestinal polypeptide, and choleocystokinin. Fewer synchronous
      spontaneous epileptiform oscillations were recorded in thalamic slices from VPA
      treated animals, and oscillation duration as well as the period of spontaneous
      and evoked oscillations were decreased. Application of the Y1 receptor inhibitor
      N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amide (BIBP3226)
      enhanced thalamic oscillations, indicating that NPY is released during those
      oscillations and acts to downregulate oscillatory strength. Chronic VPA treatment
      significantly potentiated the effect of BIBP3226 on oscillation duration but not
      on oscillation period. These results demonstrate a novel mechanism for the
      antiepileptic actions of chronic VPA therapy.

PMID- 16793889
TI  - Treatment with an estrogen receptor alpha ligand is neuroprotective in
      experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis is an inflammatory, neurodegenerative disease for which
      experimental autoimmune encephalomyelitis (EAE) is a model. Treatments with
      estrogens have been shown to decrease the severity of EAE through anti
      inflammatory mechanisms. Here we investigated whether treatment with an estrogen
      receptor alpha (ERalpha) ligand could recapitulate the estrogen-mediated
      protection in clinical EAE. We then went on to examine both anti-inflammatory and
      neuroprotective mechanisms. EAE was induced in wild-type, ERalpha-, or ERbeta
      deficient mice, and each was treated with the highly selective ERalpha agonist,
      propyl pyrazole triol, to determine the effect on clinical outcomes, as well as
      on inflammatory and neurodegenerative changes. ERalpha ligand treatment
      ameliorated clinical disease in both wild-type and ERbeta knock-out mice, but not
      in ERalpha knock-out mice, thereby demonstrating that the ERalpha ligand
      maintained ERalpha selectivity in vivo during disease. ERalpha ligand treatment
      also induced favorable changes in autoantigen-specific cytokine production in the
      peripheral immune system [decreased TNFalpha, interferon-gamma, and interleukin
      6, with increased interleukin-5] and decreased CNS white matter inflammation and
      demyelination. Interestingly, decreased neuronal staining [NeuN+ (neuronal
      specific nuclear protein)/beta3-tubulin+/Nissl], accompanied by increased
      immunolabeling of microglial/monocyte (Mac 3+) cells surrounding these abnormal
      neurons, was observed in gray matter of spinal cords of EAE mice at the earliest
      stage of clinical disease, 1-2 d after the onset of clinical signs. Treatment
      with either estradiol or the ERalpha ligand significantly reduced this gray
      matter pathology. In conclusion, treatment with an ERalpha ligand is highly
      selective in vivo, mediating both anti-inflammatory and neuroprotective effects
      in EAE.

PMID- 16793890
TI  - Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X
      C motif receptor 4 are required for migration of gonadotropin-releasing hormone
      neurons to the forebrain.
AB  - Gonadotropin-releasing hormone (GnRH) neurons migrate from the vomeronasal organ
      (VNO) in the nasal compartment to the basal forebrain in mice, beginning on
      embryonic day 11 (E11). These neurons use vomeronasal axons as guides to migrate
      through the nasal mesenchyme. Most GnRH neurons then migrate along the caudal
      branch of the vomeronasal nerve to reach the hypothalamus. We show here that
      stromal cell-derived factor-1 [SDF-1, also known as chemokine C-X-C motif ligand
      12 (CXCL12)] is expressed in the embryonic nasal mesenchyme from as early as E10
      in an increasing rostral to caudal gradient that is most intense at the border of
      the nasal mesenchyme and the telencephalon. Chemokine C-X-C motif receptor 4
      (CXCR4), the receptor for SDF-1, is expressed by neurons in the olfactory
      epithelium and VNO. Cells derived from these sensory epithelia, including
      migrating GnRH neurons and ensheathing glial precursors of the migrating mass
      (MM), also express CXCR4, suggesting that they may use SDF-1 as a chemokine. In
      support of this, most GnRH neurons of CXCR4-/- mice fail to exit the VNO at E13,
      and comparatively few GnRH neurons reach the forebrain. There is also a
      significant decrease in the total number of GnRH neurons in CXCR4-/- mice and an
      increase in cell death within the VNO relative to controls. The MM is smaller in
      CXCR4-/- mice, suggesting that some MM cells also require SDF-1/CXCR4 function
      for migration and survival.

PMID- 16793891
TI  - Sustained elevation of dendritic calcium evokes widespread endocannabinoid
      release and suppression of synapses onto cerebellar Purkinje cells.
AB  - Endocannabinoids can act as retrograde messengers that allow postsynaptic cells
      to regulate the strength of their synaptic inputs. In the cerebellum, Purkinje
      cells (PCs) release endocannabinoids through two mechanisms. Synaptic activation
      evokes local endocannabinoid release that relies on a pathway that involves the
      metabotropic glutamate receptor mGluR1 and phospholipase-C (PLC). In contrast,
      depolarization evokes endocannabinoid release from the entire dendritic arbor.
      This leads to depolarization-induced suppression of inhibitory (DSI) and
      excitatory (DSE) synapses by a mechanism that does not involve mGluR1 or PLC.
      This latter mechanism of endocannabinoid release has only been observed under
      artificial conditions that transiently elevate postsynaptic calcium to >5 microm.
      Here, we tested the possibility that this mechanism could lead to retrograde
      inhibition in response to more realistic calcium signals. At both climbing fiber
      and inhibitory synapses onto PCs, we found that prolonging the elevation of
      calcium significantly lowered the peak calcium required to evoke PLC-independent
      endocannabinoid release. This suggests that the mechanism of endocannabinoid
      release involved in DSI and DSE is likely to evoke endocannabinoid release in
      response to physiologically relevant levels of calcium. When dendritic calcium
      was elevated to 0.4-1 microm for 15 s or more, endocannabinoid release from PCs
      selectively suppressed inhibitory synapses. This suggests that inhibitory
      synapses are more sensitive to prolonged calcium increases. Thus, in contrast to
      localized retrograde inhibition evoked by synaptic activation, modest but
      sustained calcium elevation could globally suppress inhibitory synapses onto PCs.

PMID- 16793893
TI  - Phototransduction in a transgenic mouse model of Nougaret night blindness.
AB  - The Nougaret form of dominant stationary night blindness is linked to a G38D
      mutation in the rod transducin-alpha subunit (Talpha). In this study, we have
      examined the mechanism of Nougaret night blindness using transgenic mice
      expressing TalphaG38D. The biochemical, electrophysiological, and vision
      dependent behavioral analyses of the mouse model revealed a unique phenotype of
      reduced rod sensitivity, impaired activation, and slowed recovery of the
      phototransduction cascade. Two key deficiencies in TalphaG38D function, its poor
      ability to activate PDE6 (cGMP phosphodiesterase) and decreased GTPase activity,
      are found to be the major mechanisms altering visual signaling in transgenic
      mice. Despite these defects, rod-mediated sensitivity in heterozygous mice is not
      decreased to the extent seen in heterozygous Nougaret patients.

PMID- 16793894
TI  - Induction of neuregulin signaling in mouse schwann cells in vivo mimics responses
      to denervation.
AB  - Neuregulins play crucial roles in early development of Schwann cells (SCs), but
      their roles in the activities of SCs during denervation and reinnervation of
      muscle are less clear. In the present study, the Tet-On system has been used in
      transgenic mice to enable inducible expression of a mutant, constitutively active
      neuregulin receptor (ErbB2) in SCs. This induction simulates neuregulin signaling
      to these cells. Reporter transgenes were used to show a tightly regulated, SC
      selective expression in muscle. Induction leads to a number of changes in SCs at
      neuromuscular junctions that mimic the response to muscle
      denervation/reinnervation. These include process extension, soma migration, and
      proliferation. SCs also come to express nestin, a protein characteristic of their
      reaction to muscle denervation. This activation of SCs results in the sprouting
      of nerve terminals, and these sprouts follow the extensions of the SCs. However,
      these sprouts and their associated SCs disappear after the removal of the
      inducer. Last, induction of the active receptor is sufficient to rescue SCs in
      neonatal muscle from denervation-induced apoptosis. These findings show that the
      responses of SCs in muscle to denervation can be explained by induction of an
      autocrine/paracrine neuregulin signaling cascade suggested by previous molecular
      studies.

PMID- 16793892
TI  - Zinc-dependent multi-conductance channel activity in mitochondria isolated from
      ischemic brain.
AB  - Transient global ischemia is a neuronal insult that induces delayed cell death. A
      hallmark event in the early post-ischemic period is enhanced permeability of
      mitochondrial membranes. The precise mechanisms by which mitochondrial function
      is disrupted are, as yet, unclear. Here we show that global ischemia promotes
      alterations in mitochondrial membrane contact points, a rise in
      intramitochondrial Zn2+, and activation of large, multi-conductance channels in
      mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity
      was associated with enhanced protease activity and proteolytic cleavage of BCL-xL
      to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate
      deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this,
      large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL
      to control mitochondria and blocked by introduction of a functional BCL-xL
      antibody to post-ischemic mitochondria via the patch pipette. Channel activity
      was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for
      the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane.
      In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before
      ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis
      (2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a
      requirement for Zn2+. These findings reveal a novel mechanism by which ischemic
      insults disrupt the functional integrity of the outer mitochondrial membrane and
      implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial
      channels observed in post-ischemic hippocampal mitochondria.

PMID- 16793895
TI  - Earlier development of the accumbens relative to orbitofrontal cortex might
      underlie risk-taking behavior in adolescents.
AB  - Adolescence has been characterized by risk-taking behaviors that can lead to
      fatal outcomes. This study examined the neurobiological development of neural
      systems implicated in reward-seeking behaviors. Thirty-seven participants (7-29
      years of age) were scanned using event-related functional magnetic resonance
      imaging and a paradigm that parametrically manipulated reward values. The results
      show exaggerated accumbens activity, relative to prefrontal activity in
      adolescents, compared with children and adults, which appeared to be driven by
      different time courses of development for these regions. Accumbens activity in
      adolescents looked like that of adults in both extent of activity and sensitivity
      to reward values, although the magnitude of activity was exaggerated. In
      contrast, the extent of orbital frontal cortex activity in adolescents looked
      more like that of children than adults, with less focal patterns of activity.
      These findings suggest that maturing subcortical systems become
      disproportionately activated relative to later maturing top-down control systems,
      biasing the adolescent's action toward immediate over long-term gains.

PMID- 16793897
TI  - Cardiac and vascular KATP channels in rats are activated by endogenous
      epoxyeicosatrienoic acids through different mechanisms.
AB  - We have reported that epoxyeicosatrienoic acids (EETs), the cytochrome P450 (CYP)
      epoxygenase metabolites of arachidonic acid (AA), are potent sarcolemmal ATP
      sensitive K+ (KATP) channel activators. However, activation of cardiac and
      vascular KATP channels by endogenously produced EETs under physiological
      intracellular conditions has not been demonstrated and direct comparison of the
      mechanisms whereby EETs activate the KATP channels in cardiac myocytes versus
      vascular smooth muscle cells has not been made. In this study, we examined the
      effects of AA on KATP channels in freshly isolated cardiac myocytes from rats,
      wild-type (WT) and transgenic mice overexpressing CYP2J2 cDNA, and mesenteric
      arterial smooth muscle cells from rats. We also compared the activation of
      cardiac and vascular KATP channels by extracellularly and intracellularly applied
      11,12-EET. We found that 1 microm AA enhanced KATP channel activities in both
      cardiac and vascular smooth muscle cells, and the AA effects were inhibited by
      preincubation with CYP epoxygenase inhibitors. Baseline cardiac KATP current
      densities in CYP2J2 transgenic mice were 190% higher than those of WT mice, and
      both were reduced to similar levels by CYP epoxygenase inhibition. Western blot
      analysis showed that expression of Kir6.2 and SUR2A was similar between WT and
      CYP2J2 transgenic hearts. 11,12-EET (5 microm) applied intracellularly enhanced
      the KATP currents by 850% in cardiac myocytes, but had no effect in vascular
      smooth muscle cells. In contrast, 11,12-EET (5 microm) applied extracellularly
      increased KATP currents by 520% in mesenteric arterial smooth muscle cells, but
      by only 209% in cardiac myocytes. Preincubation with 100 microm m
      iodobenzylguanidine or 5 microm myristoylated PKI amide did not alter the
      activation of cardiac KATP channels by 5 microm 11,12-EET, but significantly
      inhibited activation of vascular KATP channels. Moreover, EET only enhanced the
      inward component of cardiac KATP currents, but activated both the inward and
      outward components of vascular KATP currents. Our results indicate that
      endogenously derived CYP metabolites of AA potently activate cardiac and vascular
      KATP channels. EETs regulate cardiac electrophysiology and vascular tone by KATP
      channel activation, albeit through different mechanisms: the cardiac KATP
      channels are directly activated by EETs, whereas activation of the vascular KATP
      channels by EETs is protein kinase A dependent.

PMID- 16793898
TI  - Arterial oxygenation influences central motor output and exercise performance via
      effects on peripheral locomotor muscle fatigue in humans.
AB  - Changing arterial oxygen content (C(aO(2))) has a highly sensitive influence on
      the rate of peripheral locomotor muscle fatigue development. We examined the
      effects of C(aO(2)) on exercise performance and its interaction with peripheral
      quadriceps fatigue. Eight trained males performed four 5 km cycling time trials
      (power output voluntarily adjustable) at four levels of C(aO(2)) (17.6-24.4 ml
      O(2) dl(-1)), induced by variations in inspired O(2) fraction (0.15-1.0).
      Peripheral quadriceps fatigue was assessed via changes in force output pre-
      versus post-exercise in response to supra-maximal magnetic femoral nerve
      stimulation (DeltaQ(tw); 1-100 Hz). Central neural drive during the time trials
      was estimated via quadriceps electromyogram. Increased C(aO(2)) from hypoxia to
      hyperoxia resulted in parallel increases in central neural output (43%) and power
      output (30%) during cycling and improved time trial performance (12%); however,
      the magnitude of DeltaQ(tw) (-33 to -35%) induced by the exercise was not
      different among the four time trials (P > 0.2). These effects of C(aO(2)) on time
      trial performance and DeltaQ(tw) were reproducible (coefficient of variation = 1
      6%) over repeated trials at each F(IO(2)) on separate days. In the same subjects,
      changing C(aO(2)) also affected performance time to exhaustion at a fixed work
      rate, but similarly there was no effect of Delta C(aO(2)) on peripheral fatigue.
      Based on these results, we hypothesize that the effect of C(aO(2)) on locomotor
      muscle power output and exercise performance time is determined to a significant
      extent by the regulation of central motor output to the working muscle in order
      that peripheral muscle fatigue does not exceed a critical threshold.

PMID- 16793899
TI  - High throughput protein expression screening in the nervous system--needs and
      limitations.
AB  - The cellular complexity of the brain (some estimate that there are up to 10(3)
      different cell types) is exceeded by the synaptic complexity, with each of the
      approximately 10(11) neurons in the brain having around 10(3)-10(4) synapses.
      Proteomic studies of the synapse have revealed that the postsynaptic density is
      the most complex multiprotein structure yet identified, with approximately 10(3)
      different proteins. Such studies, however, use brain tissue with many different
      regions and therefore different cell types, and there is clear potential for
      heterogeneity of protein content at different synapses within and between brain
      regions. Although large-scale mRNA-based assays are in progress to map this sort
      of complexity at the cellular level, and indeed all brain-expressed genes,
      analysis of protein distribution (at synapses and other structures) is still in
      the very early stages. We review existing large-scale protein expression studies
      and the specific technical obstacles that need to be overcome before applying the
      scaling used in nucleic acid based approaches.

PMID- 16793900
TI  - Membrane potential-regulated Ca2+ signalling in development and maturation of
      mammalian cerebellar granule cells.
AB  - In many developing neuronal cell types, the resting membrane potential is
      relatively depolarized, then gradually hyperpolarizes during the early postnatal
      period. The regulatory roles of membrane potential changes in neuronal
      development and maturation have been extensively studied in developing cerebellar
      granule cells, using primary culture under depolarizing and non-depolarizing
      conditions in combination with in vivo analysis. Depolarization enhances calcium
      entry via voltage-sensitive Ca2+ channels (VSCCs) and activates Ca2+-calmodulin
      dependent protein kinase (CaMK) and calcineurin phophatase (CaN). The activation
      of CaN induces many genes encoding extracellular and intracellular signalling
      molecules implicated in granule cell development. The inactivation of CaN in turn
      up-regulates many other genes characteristic of mature granule cells, including
      NR2C NMDA receptor and GABAAalpha1 and alpha6 receptors. The induction of NR2C
      also requires CaMK-up-regulated brain-derived neurotrophic factor (BDNF),
      indicating a convergence of signalling mechanism of the CaMK and CaN cascades.
      The inactivation of CaN maintains the phosphorylated and sumoylated form of a
      transcriptional myocyte enhances factor 2A (MEF2A) regulator. This form of MEF2A
      acts as a transcriptional repressor and is essential for the dendritic
      morphogenesis of differentiated granule cells. Collectively, the membrane
      potential change and the resulting Ca2+ signalling play a pivotal role in
      development and maturation of neuronal cells.

PMID- 16793901
TI  - Neurally mediated vasoconstriction is capable of decreasing skin blood flow
      during orthostasis in the heat-stressed human.
AB  - Given the large increase in cutaneous vascular conductance (CVC) during whole
      body heat stress, this vascular bed is important in the regulation of blood
      pressure during orthostatic stress. In this thermal state, changes in CVC are
      reported to be due to withdrawal of active vasodilator activity. The purpose of
      this study was to identify, contrary to the current line of thinking, whether
      cutaneous vasoconstrictor neural activity is enhanced and capable of contributing
      to reductions in CVC during an orthostatic challenge of heat-stressed
      individuals. Healthy normotensive subjects were pretreated, subcutaneously, with
      botulinum toxin A (BTX-A) to inhibit the release of neurotransmitters from
      cutaneous active vasodilator nerves. On the experimental day, microdialysis
      probes were placed in the BTX-A-treated site and in an adjacent untreated site.
      In protocol 1, internal temperature was elevated approximately 0.7 degrees C,
      followed by the application of lower body negative pressure (LBNP; -30 mmHg).
      LBNP reduced CVC at the BTX-A-treated sites (Delta4.2 +/- 2.9%max), as well as at
      the control site (Delta9.8 +/- 4.1%max). In protocol 2, after confirming the
      absence of cutaneous vasodilatation at the BTX-A-treated site during whole-body
      heating, CVC at this site was elevated to a similar level relative to the control
      site (55.4 +/- 13.4 versus 60.7 +/- 10.4%max, respectively) via intradermal
      administration of isoproterenol prior to LBNP. Similarly, when flow was matched
      between sites, LBNP reduced CVC at both the BTX-A-treated (Delta15.3 +/- 4.6%max)
      and the control sites (Delta8.8 +/- 5.6%max). These data suggest that the
      cutaneous vasoconstrictor system is engaged and is capable of decreasing CVC
      during an orthostatic challenge in heat-stressed individuals.

PMID- 16793903
TI  - Barium ions inhibit the dynamic response of guinea-pig corneal cold receptors to
      heating but not to cooling.
AB  - An in vitro preparation of the guinea-pig cornea was used to study the effects of
      the K+ channel blockers 4-aminopyridine (4-AP), tetraethylammonium (TEA) and Ba2+
      on nerve terminal impulses (NTIs) recorded extracellularly from cold sensory
      receptors. These receptors have an ongoing discharge of NTIs that is increased by
      cooling and decreased by heating. The K+ channel blocker 4-AP reduced the
      negative amplitude of the diphasic (positive-negative) NTIs, whereas TEA and Ba2+
      prolonged the duration of the negative component. As the shape of the NTI is
      determined by the first derivative (dV/dt) of the membrane voltage change, these
      changes in the negative component are consistent with the blockade of K+ channels
      that contribute to action potential repolarization. Only TEA changed the basal
      activity of the receptors, increasing the likelihood of burst discharges. Ba2+
      selectively reduced the response of the receptors to heating, whereas neither 4
      AP nor TEA modified the response to heating or to cooling. The findings indicate
      that K+ channels blocked by 4-AP, TEA and Ba2+ contribute to action potential
      repolarization in corneal cold receptors, and that ionic mechanisms that underlie
      the reduction in NTI frequency in response to heating differ from those that
      increase activity in response to cooling.

PMID- 16793902
TI  - Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A
      dependent mechanisms in rats and mice.
AB  - Proteases that are released during inflammation and injury cleave protease
      activated receptor 2 (PAR2) on primary afferent neurons to cause neurogenic
      inflammation and hyperalgesia. PAR2-induced thermal hyperalgesia depends on
      sensitization of transient receptor potential vanilloid receptor 1 (TRPV1), which
      is gated by capsaicin, protons and noxious heat. However, the signalling
      mechanisms by which PAR2 sensitizes TRPV1 are not fully characterized. Using
      immunofluorescence and confocal microscopy, we observed that PAR2 was colocalized
      with protein kinase (PK) Cepsilon and PKA in a subset of dorsal root ganglia
      neurons in rats, and that PAR2 agonists promoted translocation of PKCepsilon and
      PKA catalytic subunits from the cytosol to the plasma membrane of cultured
      neurons and HEK 293 cells. Subcellular fractionation and Western blotting
      confirmed this redistribution of kinases, which is indicative of activation.
      Although PAR2 couples to phospholipase Cbeta, leading to stimulation of PKC, we
      also observed that PAR2 agonists increased cAMP generation in neurons and HEK 293
      cells, which would activate PKA. PAR2 agonists enhanced capsaicin-stimulated
      increases in [Ca2+]i and whole-cell currents in HEK 293 cells, indicating TRPV1
      sensitization. The combined intraplantar injection of non-algesic doses of PAR2
      agonist and capsaicin decreased the latency of paw withdrawal to radiant heat in
      mice, indicative of thermal hyperalgesia. Antagonists of PKCepsilon and PKA
      prevented sensitization of TRPV1 Ca2+ signals and currents in HEK 293 cells, and
      suppressed thermal hyperalgesia in mice. Thus, PAR2 activates PKCepsilon and PKA
      in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia.
      These mechanisms may underlie inflammatory pain, where multiple proteases are
      generated and released.

PMID- 16793904
TI  - Loading rat heart myocytes with Mg2+ using low-[Na+] solutions.
AB  - The objective of our study was to investigate how Mg2+ enters mammalian cardiac
      cells. During this work, we found evidence for a previously undescribed route for
      Mg2+ entry, and now provide a preliminary account of its properties. Changes in
      Mg2+ influx into rat ventricular myocytes were deduced from changes in
      intracellular ionized Mg2+ concentration ([fMg2+]i) measured from the
      fluorescence of mag-fura-2 loaded into isolated cells. Superfusion of myocytes at
      37 degrees C with Ca2+-free solutions with both reduced [Na+] and raised [Mg2+]
      caused myocytes to load with Mg2+. Uptake was seen with solutions containing 5 mm
      Mg2+ and 95 mm Na+, and increased linearly with increasing extracellular [Mg2+]
      or decreasing extracellular [Na+]. It was very sensitive to temperature (Q(10) >
      9, 25--37 degrees C), was observed even in myocytes with very low Na+ contents,
      and stopped abruptly when external [Na+] was returned to normal. Uptake was
      greatly reduced by imipramine or KB-R7943 if these were added when [fMg2+]i was
      close to the physiological level, but was unaffected if they were applied when
      [fMg2+]i was above 2 mm. Uptake was also reduced by depolarizing the membrane
      potential by increasing extracellular [K+] or voltage clamp to 0 mV. We suggest
      that initial Mg2+ uptake may involve several transporters, including reversed Na+
      Mg2+ antiport and, depending on the exact conditions, reversed Na+-Ca2+ antiport.
      The ensuing rise of [fMg2+]i, in conjunction with reduced [Na+], may then
      activate a new Mg2+ transporter that is highly sensitive to temperature, is
      insensitive to imipramine or KB-R7943, but is inactivated by depolarization.

PMID- 16793905
TI  - Evidence for both adenosine A1 and A2A receptors activating single vagal sensory
      C-fibres in guinea pig lungs.
AB  - We addressed the hypothesis that single vagal afferent C-fibres can be stimulated
      via either the adenosine A1 or A2A receptor subtypes. The effect of adenosine on
      the nerve terminals of vagal sensory nerve subtypes was evaluated in an ex vivo
      perfused guinea pig lung preparation using extracellular recording techniques.
      Adenosine (10 microm) consistently evoked action potential discharge in lung C
      fibre terminals arising from the nodose ganglia, but failed to evoke action
      potential discharge in most jugular ganglion C-fibres. Adenosine also failed to
      activate stretch-sensitive nodose A-fibres in the lungs. The selective A1
      antagonist DPCPX (0.1 microm) or the selective A2A antagonist SCH 58261 (0.1
      microm) partially inhibited the nodose C-fibre activation by adenosine, and the
      combination of both antagonists almost completely inhibited the response. The
      adenosine-induced action potential discharge in nodose C-fibres was mimicked by
      either the selective A1 agonist CCPA (1 microm) or the selective A2A agonist CGS
      21680 (1 microm). Single cell PCR techniques revealed that adenosine A1 and A2A
      receptor mRNA was expressed in individual nodose neurons retrogradely labelled
      from the lungs. The gramicidin-perforated patch clamp technique on neurons
      retrogradely labelled from the lungs was employed to study the functional
      consequence of adenosine receptor agonists directly on neuronal membrane
      properties. Both the selective A1 agonist CCPA (1 microm) and the selective A2A
      agonist CGS 21680 (1 microm) depolarized the airway-specific, capsaicin
      sensitive, nodose neurons to action potential threshold. The data support the
      hypothesis that adenosine selectively depolarizes vagal nodose C-fibre terminals
      in the lungs to action potential threshold, by stimulation of both adenosine A1
      and A2A receptor subtypes located in the neuronal membrane.

PMID- 16793906
TI  - Activated calcineurin ameliorates contraction-induced injury to skeletal muscles
      of mdx dystrophic mice.
AB  - Utrophin expression is regulated by calcineurin and up-regulating utrophin can
      decrease the susceptibility of dystrophic skeletal muscle to contraction-induced
      injury. We overexpressed the constitutively active calcineurin-A alpha in
      skeletal muscle of mdx dystrophic mice (mdx CnA*) and examined the tibialis
      anterior muscle to determine whether the presence of activated calcineurin
      promotes resistance to muscle damage after lengthening contractions. Two
      stretches (10 s apart) of 40% strain relative to muscle fibre length were
      initiated from the plateau of a maximal isometric tetanic contraction. Muscle
      damage was assessed 1, 5 and 15 min later by the deficit in maximum isometric
      force and by quantifying the proportion of muscle fibres staining positive for
      intracytoplasmic albumin. The force deficit at all time points after the
      lengthening contractions was approximately 80% in mdx muscles and 30% in mdx CnA*
      muscles. The proportion of albumin-positive fibres was significantly less in
      control and injured muscles from mdx CnA* mice than from mdx mice. Compared with
      mdx mice, mean fibre cross-sectional area was 50% less in muscles from mdx CnA*
      mice. Furthermore, muscles from mdx CnA* mice exhibited a higher proportion of
      fibres expressing the slow(er) myosin heavy chain (MyHC) I and IIa isoforms,
      prolonged contraction and relaxation times, lower absolute and normalized maximum
      forces, and a clear leftward shift of the frequency-force relationship with
      greater force production at lower stimulation frequencies. These are structural
      and functional markers of a slower muscle phenotype. Taken together, our findings
      show that muscles from mdx CnA* mice have a smaller mean fibre cross-sectional
      area, a greater sarcolemmal to cytoplasmic volume ratio, and an increase in
      utrophin expression, promoting an attenuated susceptibility to contraction
      induced injury. We conclude that increased calcineurin activity may confer
      functional benefits to dystrophic skeletal muscles.

PMID- 16793907
TI  - Efficacy and connectivity of intracolumnar pairs of layer 2/3 pyramidal cells in
      the barrel cortex of juvenile rats.
AB  - Synaptically coupled layer 2/3 (L2/3) pyramidal neurones located above the same
      layer 4 barrel ('barrel-related') were investigated using dual whole-cell voltage
      recordings in acute slices of rat somatosensory cortex. Recordings were followed
      by reconstructions of biocytin-filled neurones. The onset latency of unitary
      EPSPs was 1.1 +/- 0.4 ms, the 20-80% rise time was 0.7 +/- 0.2 ms, the average
      amplitude was 1.0 +/- 0.7 mV and the decay time constant was 15.7 +/- 4.5 ms. The
      coefficient of variation (c.v.) of unitary EPSP amplitudes decreased with
      increasing EPSP peak and was 0.33 +/- 0.18. Bursts of APs in the presynaptic
      pyramidal cell resulted in EPSPs that, over a wide range of frequencies (5-100
      Hz), displayed amplitude depression. Anatomically the barrel-related pyramidal
      cells in the lower half of layer 2/3 have a long apical dendrite with a small
      terminal tuft, while pyramidal cells in the upper half of layer 2/3 have shorter
      and often more 'irregularly' shaped apical dendrites that branch profusely in
      layer 1. The number of putative excitatory synaptic contacts established by the
      axonal collaterals of a L2/3 pyramidal cell with a postsynaptic pyramidal cell in
      the same column varied between 2 and 4, with an average of 2.8 +/- 0.7 (n = 8
      pairs). Synaptic contacts were established predominantly on the basal dendrites
      at a mean geometric distance of 91 +/- 47 mum from the pyramidal cell soma. L2/3
      to-L2/3 connections formed a blob-like innervation domain containing 2.8 mm of
      the presynaptic axon collaterals with a bouton density of 0.3 boutons per mum
      axon. Within the supragranular layers of its home column a single L2/3 pyramidal
      cell established about 900 boutons suggesting that 270 pyramidal cells in layer
      2/3 are innervated by an individual pyramidal cell. In turn, a single pyramidal
      cell received synaptic inputs from 270 other L2/3 pyramidal cells. The
      innervation domain of L2/3-to-L2/3 connections superimposes almost exactly with
      that of L4-to-L2/3 connections. This suggests that synchronous feed-forward
      excitation of L2/3 pyramidal cells arriving from layer 4 could be potentially
      amplified in layer 2/3 by feedback excitation within a column and then relayed to
      the neighbouring columns.

PMID- 16793908
TI  - Moderate antiangiogenic activity by local, transgenic expression of endostatin in
      Rip1Tag2 transgenic mice.
AB  - Many previous reports have demonstrated that systemic administration of
      endostatin (ES), a proteolytic cleavage product of collagen type XVIII and an
      endogenous angiogenesis inhibitor, represses tumor angiogenesis in different
      preclinical tumor models with varying efficacy. For example, systemic delivery of
      recombinant ES to rat insulin promoter 1 (Rip1)T-antigen 2 (Tag2)-transgenic
      mice, a mouse model of pancreatic beta-cell carcinogenesis, has repressed tumor
      angiogenesis efficiently and with it, tumor growth. Here, we report that the
      transgenic expression of ES in Rip1ES-transgenic mice only interferes moderately
      with tumor growth in Rip1Tag2;Rip1ES double-transgenic mice. Tumor incidence is
      not reduced by the local expression of ES, and tumor outgrowth and progression to
      tumor malignancy are only retarded slightly. A significant effect of local ES
      expression on tumor angiogenesis is only apparent during the early stages of
      tumor development, where less angiogenic hyperplastic lesions are observed.
      Although efficiently produced and secreted by transgenic beta cells, locally
      expressed ES appears to be sequestered in the microenvironment, and its systemic
      levels are not increased. The results indicate that the antiangiogenic functions
      of ES critically depend on the mode of delivery and the site of expression:
      although its systemic application represses tumor angiogenesis and tumor growth
      efficiently, locally expressed ES appears to be less effective, and hence,
      additional mechanisms of solubilization or activation of latent ES seem to be
      required. These results have important implications about the modes of delivery
      used in antiangiogenic, therapeutic strategies, which are based on the
      antiangiogenic activities of ES.

PMID- 16793909
TI  - Mucosal IL-8 and TGF-beta recruit blood monocytes: evidence for cross-talk
      between the lamina propria stroma and myeloid cells.
AB  - The lamina propria of the gastrointestinal mucosa contains the largest population
      of mononuclear phagocytes in the body, yet little is known about the cellular
      mechanisms that regulate mononuclear cell recruitment to noninflamed and inflamed
      intestinal mucosa. Here, we show that intestinal macrophages do not proliferate.
      We also show that a substantial proportion of intestinal macrophages express
      chemokine receptors for interleukin (IL)-8 and transforming growth factor-beta
      (TGF-beta), and a smaller proportion expresses receptors for N-formylmethionyl
      leucyl-phenylalanine and C5a, but, surprisingly, they do not migrate to the
      corresponding ligands. In contrast, autologous blood monocytes, which express the
      same receptors, do migrate to the ligands. Blood monocytes also migrate to
      conditioned medium (CM) derived from lamina propria extracellular matrix, which
      we show contains IL-8 and TGF-beta that are produced by epithelial cells and
      lamina propria mast cells. This migration is specific to IL-8 and TGF-beta, as
      preincubation of the stroma-CM with antibodies to IL-8 and TGF-beta significantly
      blocked monocyte chemotaxis to the stromal products. Together, these findings
      indicate that blood monocytes are the exclusive source of macrophages in the
      intestinal mucosa and underscore the central role of newly recruited blood
      monocytes in maintaining the macrophage population in noninflamed mucosa and in
      serving as the exclusive source of macrophages in inflamed mucosa.

PMID- 16793911
TI  - Paneth cells: leukocyte-like mediators of innate immunity in the intestine.
AB  - Paneth cells are secretory intestinal epithelial cells located at the base of the
      crypts of Lieberkuhn in the small intestine. They display prominent cytoplasmic
      granules, containing antibacterial proteins such as lysozyme, secretory
      phospholipase A2 type IIA, and alpha-defensins, which are released into the
      intestinal lumen in response to a range of stimuli. In this, they resemble
      circulating leukocytes, which also elaborate and secrete lysozyme and alpha
      defensins as part of an antibacterial defense function, and the resemblance is
      sustained at other levels. The cells also strongly and specifically express the
      NOD2 gene product, one of an emerging family of critical, intracellular mediators
      of innate immune responses, which is also highly expressed in peripheral blood
      mononuclear cells, and they express RNA for tumor necrosis factor alpha, a major
      myelomonocytic cell-derived cytokine, which has a crucial role in the
      pathogenesis of diseases such as rheumatoid arthritis and Crohn's disease (CD).
      Thus, these cells, which are derived from the pluripotent intestinal epithelial
      stem-cell lineage, are sessile, resident host-defense cells, which may share with
      leukocytes the beneficial function of secreting antimicrobial peptides, as well
      as the potentially harmful capacity for promoting inflammation and tissue damage.
      Paneth cells are most abundant in the distal small intestine, which is the region
      most frequently affected by CD, and there is great interest in the potential role
      of these cells in this condition. This brief review summarizes current knowledge
      and speculates on how the study of these fascinating cells might be advanced.

PMID- 16793910
TI  - The human cationic host defense peptide LL-37 mediates contrasting effects on
      apoptotic pathways in different primary cells of the innate immune system.
AB  - The human cathelicidin LL-37 is a cationic host defense peptide (antimicrobial
      peptide) expressed primarily by neutrophils and epithelial cells. This peptide,
      up-regulated under conditions of inflammation, has immunomodulatory and
      antimicrobial functions. We demonstrate that LL-37 is a potent inhibitor of human
      neutrophil apoptosis, signaling through P2X(7) receptors and G-protein-coupled
      receptors other than the formyl peptide receptor-like-1 molecule. This process
      involved modulation of Mcl-1 expression, inhibition of BID and procaspase-3
      cleavage, and the activation of phosphatidylinositol-3 kinase but not the
      extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase
      pathway. In contrast to the inhibition of neutrophil apoptosis, LL-37 induced
      apoptosis in primary airway epithelial cells, demonstrating alternate
      consequences of LL-37-mediated modulation of apoptotic pathways in different
      human primary cells. We propose that these novel immunomodulatory properties of
      LL-37 contribute to peptide-mediated enhancement of innate host defenses against
      acute infection and are of considerable significance in the development of such
      peptides and their synthetic analogs as potential therapeutics for use against
      multiple antibiotic-resistant infectious diseases.

PMID- 16793912
TI  - Tumor and lymph node lymphangiogenesis--impact on cancer metastasis.
AB  - The extent of lymph node (LN) metastasis is a major determinant for the staging
      and the prognosis of most human malignancies and often guides therapeutic
      decisions. Although the clinical significance of LN involvement is well
      documented, little has been known about the molecular mechanisms that promote
      tumor spread via lymphatic vessels to sentinel and distal LN and beyond. However,
      recent discoveries have identified novel lymphatic-specific markers, and the
      newly discovered lymphangiogenesis factors vascular endothelial growth factor-C
      (VEGF-C) and VEGF-D were found to promote tumor-associated lymphatic vessel
      growth in mouse tumor models, leading to enhanced tumor spread to sentinel LN.
      Our recent findings indicate that VEGF-A also acts as a potent tumor
      lymphangiogenesis factor that promotes lymphatic tumor spread. VEGF-A
      overexpressing primary tumors induced sentinel LN lymphangiogenesis even before
      metastasizing and maintained their lymphangiogenic activity after metastasis to
      draining LN. Our recent studies showed that primary human melanomas that later
      metastasized were characterized by increased lymphangiogenesis and that the
      degree of tumor lymphangiogenesis can serve as a novel predictor of LN metastasis
      and overall patient survival, independently of tumor thickness. Tumor
      lymphangiogenesis also significantly predicted the presence of sentinel LN
      metastases at the time of surgical excision of the primary melanoma. Together,
      these findings suggest that tumor lymphangiogenesis actively contributes to
      cancer dissemination, that blockade of lymphatic vessel growth might inhibit
      tumor metastasis to LN, and that the extent of tumor-associated lymphangiogenesis
      could serve as a novel, prognostic parameter for the metastatic risk of human
      cancers.

PMID- 16793913
TI  - Up-regulation of ERK and p38 MAPK signaling pathways by hepatitis C virus E2
      envelope protein in human T lymphoma cell line.
AB  - Hepatitis C virus (HCV) infection correlates with human immune disorders
      characterized by abnormal activation and proliferation of lymphocytes.
      Interaction of HCV major envelope protein E2 with susceptible cells occurs at an
      early stage of the viral infection. HCV tropism for susceptible cells may elicit
      cellular signaling events implicated in the viral pathogenicity, and E2 protein
      is known to be responsible for the tropism. We documented previously that HCV E2
      protein was capable of activating extracellular signal-regulated kinase (ERK) in
      human hepatoma Huh-7 cells. Here, ERK and p38 mitogen-activated protein kinase
      (MAPK) signaling pathways were investigated in human T lymphoma cell line Molt-4
      in response to HCV E2 protein. Binding of HCV E2 protein to Molt-4 cells was
      detectable, and such interaction was a determinant for recognition and delivery
      of the E2 signal to intracellular pathways. Activation of ERK and p38 MAPK was
      specifically induced following the HCV E2-cell interaction. CD81 and low-density
      lipoprotein receptor (LDLR), proposed cellular receptors for HCV, were expressed
      naturally on Molt-4 cells. CD81 and LDLR were shown to mediate HCV E2-induced
      activation of ERK and p38 MAPK. In CD81-deficient U937 cells, levels of ERK and
      p38 MAPK activation and cell proliferation induced by HCV E2 protein were lower
      than those in Molt-4 cells. Furthermore, cell proliferation and secretion of
      interferon-gamma and interleukin-10 by Molt-4 cells were promoted by HCV E2
      protein. Therefore, ERK and p38 MAPK signaling pathways were up-regulated by HCV
      E2 protein without synergetic stimulation, which was accompanied by alterations
      of cell behavior.

PMID- 16793914
TI  - The source of APRIL up-regulation in human solid tumor lesions.
AB  - Abundant mRNA expression for a proliferation-inducing ligand (APRIL) from tumor
      necrosis factor (TNF) family is observed in many solid tumors. Here, we analyzed
      in situ the cellular source of APRIL in human solid tumors with anti-APRIL
      antibodies. In most cases, neutrophils present in the tumor stroma constituted
      the main source of APRIL. In cutaneous lesions such as melanoma or basal cell
      carcinoma, tumor-adjacent keratinocytes also produced APRIL. APRIL production by
      tumor cells themselves was a rare event, only observed in urothelial bladder
      cancer and squamous cell carcinoma. Detailed analysis revealed that APRIL
      dissociated from producing cells, and secreted APRIL was retained in the tumor
      lesions. A direct binding onto tumor cells via heparan sulfate proteoglycans
      (HSPG) was observed in in vitro experiments and confirmed in situ. Taken
      together, our analysis indicates a potential role for HSPG/APRIL interactions in
      the development of solid tumors.

PMID- 16793915
TI  - Neutrophil apoptosis in rheumatoid arthritis is regulated by local oxygen
      tensions within joints.
AB  - Neutrophils are normally short-lived cells and die by apoptosis, but when
      recruited into tissues, their apoptosis is delayed, and they survive for much
      longer time periods. In inflammatory diseases, such as rheumatoid arthritis (RA),
      this delayed apoptosis may lead to increased tissue damage and a failure of the
      inflammation to resolve. However, there are conflicting reports in the literature
      as to whether neutrophil apoptosis is delayed or accelerated in rheumatoid
      joints. In this report, we show that neutrophils isolated from the synovial fluid
      (SF) of patients with RA show accelerated rates of apoptosis when incubated ex
      vivo and that SF, despite containing a variety of antiapoptotic cytokines, is
      proapoptotic. Paradoxically, levels of the key neutrophil survival protein Mcl-1
      are elevated in freshly isolated SF neutrophils compared with matched peripheral
      blood samples from the same patients, indicating that delayed neutrophil
      apoptosis has been signaled in vivo as the cells enter the joints. However, when
      SF was added to neutrophils and incubated under hypoxia (1% O(2)), conditions
      known to exist in vivo within joints, the SF was antiapoptotic. These data reveal
      that the rheumatoid synovial joint contains a complex mixture of pro- and
      antiapoptotic factors and that the low, local oxygen tensions that exist within
      these joints can exert profound effects on neutrophil survival. These experiments
      also highlight the importance of performing in vitro experiments under laboratory
      conditions that closely mimic those that occur in vivo; otherwise, misleading
      conclusions may be drawn.

PMID- 16793916
TI  - Aspergillus fumigatus extract differentially regulates antigen-specific CD4+ and
      CD8+ T cell responses to promote host immunity.
AB  - Invasive aspergillosis is a major cause of morbidity and mortality in the
      severely immunocompromised. The paucity of information about the mechanisms by
      which Aspergillus-derived factors regulate antigen-specific T cell responses in
      vivo poses a significant hurdle for devising effective immunization strategies to
      treat or prevent aspergillosis. By monitoring adoptively transferred T cell
      receptor transgenic, naive CD4+ (OT-II) and CD8+ (OT-I) T cells specific for
      distinct peptides of a nominal antigen, chicken ovalbumin (OVA), we demonstrate
      that sensitization with Aspergillus fumigatus (Af) extract plus OVA protein
      considerably enhances OT-I and OT-II T cell activation, which results in clonal
      expansion, primarily as a result of increased proliferation. The sensitization
      provided by Af extract promotes OT-I expansion accompanied by differentiation
      into interferon-gamma-producing cytotoxic cells. It is surprising that no
      effector differentiation of the induced OT-II response was observed. Moreover,
      the Af extract-induced OT-I and OT-II T cell expansion was transient, as
      considerable contraction in the numbers of detectable OT-I and OT-II T cells was
      evidenced by Day 10. In agreement with these observations, sensitization with Af
      extract plus OVA marginally promoted host immunity against an OVA-expressing
      thymoma (E.G7) challenge, and the protection was enhanced by resensitization with
      Af extract and OVA. Our results demonstrate the ability of Af extract to
      differentially regulate antigen-specific CD4+ and CD8+ T cell responses,
      resulting in limited augmentation of host immunity. This information suggests
      that strategies to target CD4+ T cell effector maturation may promote host
      immunity to Aspergillus and unexpectedly demonstrates the use for Af extract as a
      CD8+ T cell adjuvant.

PMID- 16793917
TI  - Interview with Dr. Philip Griebel regarding Pivotal Advance: passively acquired
      membrane proteins alter the functional capacity of bovine polymorphonuclear
      cells. Interview by Helene F. Rosenberg.

PMID- 16793918
TI  - Pivotal Advance: passively acquired membrane proteins alter the functional
      capacity of bovine polymorphonuclear cells.
AB  - We have previously shown that bovine polymorphonuclear cells (PMNs) have an
      impressive capacity to passively acquire membrane lipids and proteins from
      apoptotic cells. The present study used confocal microscopy to analyze the
      interaction between PMNs and a variety of donor cells, and assays were used to
      determine if passively acquired membrane proteins altered PMN biology. Confocal
      microscopy revealed that direct cell-cell contact and microparticles shed by
      donor cells may be a source of passively acquired membranes and integral membrane
      proteins, which then integrate into the PMN plasma membrane. Donor cells
      expressing green fluorescent protein in their cytoplasm were also used to
      demonstrate the transfer of cytoplasmic proteins from donor cells to PMNs. The
      functional consequences of passive membrane protein acquisition by PMNs were then
      investigated using two distinct systems. First, PMNs were incubated with
      membranes isolated from an adenovirus-permissive cell line, and this passive
      transfer of cell membranes significantly increased adenovirus infection of PMNs.
      Second, major histocompatibility complex (MHC) class II molecules were passively
      transferred from ovine B cells to bovine PMNs, and PMNs with ovine MHC class II
      on their surface were able to induce a proliferative response and increased
      cytokine gene expression in alloreactive bovine T cell lines. In conclusion,
      passively acquired membrane proteins integrated into the plasma membrane of
      bovine PMNs and altered the functional capacity of these cells.

PMID- 16793919
TI  - Inflammatory processes triggered by TCR engagement or by local cytokine
      expression: differences in profiles of gene expression and infiltrating cell
      populations.
AB  - Immune cell-mediated inflammatory responses are triggered by TCR engagement with
      the target antigen, the initial event that brings about the complex sequence of
      events of the inflammatory process. Another form of inflammation is induced by
      local expression of certain cytokines. Unlike the former form of inflammation,
      little is known about the basic features of the cytokine-induced responses. Here,
      we analyzed tissue morphology, the infiltrating cells, and up-regulated,
      inflammation-related genes in mouse eyes in which inflammation is triggered by
      local transgenic (Tg) expression of cytokines and compared these features with
      those in eyes with experimental autoimmune uveitis (EAU), in which inflammation
      is initiated by engagement of TCR on sensitized T cells with their target
      antigen, followed by the well-defined, subsequent cytokine production. Eyes of
      IFN-gamma Tg mice exhibited severe, morphological changes but essentially no
      inflammation, and intense inflammation was found in eyes of interleukin (IL)-1 or
      IL-7 Tg mice. The cellular infiltration in eyes of these latter two lines of Tg
      mice resembled that in eyes with EAU by including many CD4 cells, but unlike in
      EAU, the infiltration in Tg eyes contained large proportions of B cells and only
      small numbers of macrophages. Real-time PCR analysis of eye RNA revealed
      differences among the disease models in the expression profiles of various
      inflammation-related genes. It is interesting that a bias toward T helper cell
      type 1 immunity (high IFN-gamma, RANTES/CCL5, MIG/CXCL9, and T-bet but low IL-4,
      IL-5, and GATA-3 transcripts) was found in EAU eyes but not in eyes of IL-1 and
      IL-7 Tg mice. The results thus show that similar to TCR engagement, local
      expression of certain cytokines triggers a complex, subsequent production of
      numerous inflammation-related molecules, but features of the ensued inflammatory
      process are determined by the triggering mechanism.

PMID- 16793920
TI  - Eisenmenger syndrome: towards identifying the risk factors for death.

PMID- 16793921
TI  - Presentation, survival prospects, and predictors of death in Eisenmenger
      syndrome: a combined retrospective and case-control study.
AB  - AIMS: To characterize contemporary Eisenmenger patients at a large centre for
      adult congenital heart disease, assess survival prospects, and identify
      predictors of death in this population. METHODS AND RESULTS: All Eisenmenger
      patients under follow-up at our centre since 2000 (n=171, mean age 37+/-12 years)
      were included. To identify predictors of mortality, a case-control study was
      performed. Data including symptoms, functional class, medication, laboratory, and
      electrocardiographic and echocardiographic parameters are presented. Iron
      deficiency was common and strongly related to phlebotomy (relative risk 4.1,
      P<0.0001). Haemoglobin concentration was inversely related to arterial oxygen
      saturations in iron-replete patients (P<0.001) but not in iron-deficient
      patients. During a median follow-up of 67 months, 20 patients died. Survival at
      40, 50, and 60 years of age was 94, 74, and 52%, respectively. When compared with
      healthy individuals, median survival was reduced by approximately 20 years in
      Eisenmenger patients and was worst in those with complex lesions. Predictors of
      mortality included functional class, signs of heart failure, history of clinical
      arrhythmia, QRS duration and QTc interval, and low serum albumin and potassium
      levels. CONCLUSION: Despite good short-term prognosis, life expectancy is
      markedly reduced in Eisenmenger patients. Markers of heart failure and parameters
      associated with arrhythmia are of prognostic value in terms of mortality and may
      guide clinicians caring for Eisenmenger patients.

PMID- 16793923
TI  - Allosteric mechanism in AMPA receptors: a FRET-based investigation of
      conformational changes.
AB  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are the
      primary mediators of fast excitatory synaptic transmission in the mammalian CNS.
      Structures of the extracellular ligand-binding domain suggest that the extent of
      cleft closure in the ligand-binding domain controls the extent of activation of
      the receptor. Here we have developed a fluorescence resonance energy transfer
      based probe that allows us to study the extent of cleft closure in the isolated
      ligand-binding domain in solution. These investigations show that the wild-type
      protein exhibits a graded cleft closure that correlates to the extent of
      activation, which is in qualitative agreement with the crystal structures.
      However, the changes in extent of cleft closure between the apo and agonist-bound
      states are smaller than that observed in the crystal structures. We have also
      used this method to study the L650T mutant and show that in solution the alpha
      amino-5-methyl-3-hydroxy-4-isoxazole propionate-bound form of this mutant exists
      primarily in a conformation that is more closed than predicted based on the
      activity, indicating that the degree of cleft closure alone cannot be used as a
      measure of extent of activation of the receptor, and there are possibly other
      mechanisms in addition to cleft closure that mediate the subtleties in extent of
      activation by a given agonist.

PMID- 16793922
TI  - Identification of a Hoxc8-regulated transcriptional network in mouse embryo
      fibroblast cells.
AB  - The transcription factor, Hoxc8, is a member of the homeobox gene family that is
      vital for growth and differentiation. Previously, we identified 34 genes whose
      expression levels were changed at least 2-fold by forced expression of Hoxc8 in
      C57BL/6J mouse embryo fibroblast cells using a mouse 16,463-gene oligonucleotide
      microarray. In the present study, we used the combined power of microarray
      profiling, global Hoxc8 DNA-binding site analysis, and high-throughput chromatin
      immunoprecipitation assays to identify direct and biologically relevant targets
      of Hoxc8 in vivo. Here we show that 19 of the 34 responsive genes contain Hoxc8
      consensus DNA-binding sequence(s) in their regulatory regions. Chromatin
      immunoprecipitation analysis indicated that Hoxc8-DNA interaction was detected in
      five of the 19 candidate genes. All of these five target genes have been
      implicated in oncogenesis, cell adhesion, proliferation, and apoptosis. Overall,
      the genes described here should aid in the understanding of global regulatory
      networks of Hox genes and to provide valuable insight into the molecular basis of
      Hoxc8 in development and carcinogenesis.

PMID- 16793924
TI  - Attentional modulation of sensorimotor processes in the absence of perceptual
      awareness.
AB  - Attention modulates visual perception and is generally considered inextricably
      linked with conscious awareness: we become aware of stimuli as we attend to them,
      and we attend to stimuli as we become aware of them. Recent evidence suggests
      that attention can also modulate the effects of stimuli that remain invisible,
      and a natural explanation is that attention enhances weak perceptual
      representations, bringing them closer to conscious threshold even if they do not
      reach that threshold. However, there is also the possibility that attention may
      modulate neural processes that are entirely separate from those supporting
      conscious perception: sensorimotor mechanisms that do not create awareness
      however much they are enhanced. Here we provide evidence in support of this
      second hypothesis by showing that attentional cueing can modulate the behavioral
      response to invisible stimuli in a way that is distinct from enhancing their
      visibility. We used a masked-prime paradigm that produces a negative or positive
      compatibility effect depending on the perceptual strength (duration or
      brightness) of the prime. We found that attention enhanced the effect of both
      visible and invisible primes and also increased the likelihood of detecting the
      prime (i.e., boosted perceptual strength). Crucially, the pattern of attentional
      influence on priming could not be explained by attentional modulation of the
      prime's perceptual strength but was predicted by a direct attentional influence
      on the nonconscious priming process itself. Therefore, in addition to regulating
      what we perceive, attention seems to influence our behavior through sensorimotor
      processes that are not involved in conscious awareness.

PMID- 16793925
TI  - Nutrient additions to a tropical rain forest drive substantial soil carbon
      dioxide losses to the atmosphere.
AB  - Terrestrial biosphere-atmosphere carbon dioxide (CO(2)) exchange is dominated by
      tropical forests, where photosynthetic carbon (C) uptake is thought to be
      phosphorus (P)-limited. In P-poor tropical forests, P may also limit organic
      matter decomposition and soil C losses. We conducted a field-fertilization
      experiment to show that P fertilization stimulates soil respiration in a lowland
      tropical rain forest in Costa Rica. In the early wet season, when soluble organic
      matter inputs to soil are high, P fertilization drove large increases in soil
      respiration. Although the P-stimulated increase in soil respiration was largely
      confined to the dry-to-wet season transition, the seasonal increase was
      sufficient to drive an 18% annual increase in CO(2) efflux from the P-fertilized
      plots. Nitrogen (N) fertilization caused similar responses, and the net increases
      in soil respiration in response to the additions of N and P approached annual
      soil C fluxes in mid-latitude forests. Human activities are altering natural
      patterns of tropical soil N and P availability by land conversion and enhanced
      atmospheric deposition. Although our data suggest that the mechanisms driving the
      observed respiratory responses to increased N and P may be different, the large
      CO(2) losses stimulated by N and P fertilization suggest that knowledge of such
      patterns and their effects on soil CO(2) efflux is critical for understanding the
      role of tropical forests in a rapidly changing global C cycle.

PMID- 16793926
TI  - Cardiac glycosides provide neuroprotection against ischemic stroke: discovery by
      a brain slice-based compound screening platform.
AB  - We report here the results of a chemical genetic screen using small molecules
      with known pharmacologies coupled with a cortical brain slice-based model for
      ischemic stroke. We identified a small-molecule compound not previously
      appreciated to have neuroprotective action in ischemic stroke, the cardiac
      glycoside neriifolin, and demonstrated that its properties in the brain slice
      assay included delayed therapeutic potential exceeding 6 h. Neriifolin is
      structurally related to the digitalis class of cardiac glycosides, and its
      putative target is the Na(+)/K(+)-ATPase. Other cardiac glycoside compounds
      tested also showed neuroprotective activity, although with lower apparent
      potencies. In subsequent whole-animal studies, we found that neriifolin provided
      significant neuroprotection in a neonatal model of hypoxia/ischemia and in a
      middle cerebral artery occlusion model of transient focal ischemia. The
      neuroprotective potential of Na(+)/K(+)-ATPase is of particular interest because
      of its known "druggability"; indeed, Food and Drug Administration-approved, small
      molecule compounds such as digitoxin and digoxin have been in clinical usage for
      congestive heart failure and arrhythmias for several decades. Thus, an existing
      cardiac glycoside or closely related compound could provide an accelerated path
      toward clinical trial testing for ischemic stroke. Our findings underscore the
      important role that hypothesis-neutral, high-content, tissue-based screens can
      play in the identification of new candidate drugs and drug targets for the
      treatment of diseases for which validated therapeutic pathways are not currently
      available.

PMID- 16793927
TI  - The consensus mechanics of cultured mammalian cells.
AB  - Although understanding cells' responses to mechanical stimuli is seen as
      increasingly important for understanding cell biology, how to best measure,
      interpret, and model cells' mechanical properties remains unclear. We determine
      the frequency-dependent shear modulus of cultured mammalian cells by using four
      different methods, both unique and well established. This approach clarifies the
      effects of cytoskeletal heterogeneity, ATP-dependent processes, and cell regional
      variations on the interpretation of such measurements. Our results clearly
      indicate two qualitatively similar, but distinct, mechanical responses,
      corresponding to the cortical and intracellular networks, each having an unusual,
      weak power-law form at low frequency. The two frequency-dependent responses we
      observe are remarkably similar to those reported for a variety of cultured
      mammalian cells measured with different techniques, suggesting it is a useful
      consensus description. Finally, we discuss possible physical explanations for the
      observed mechanical response.

PMID- 16793928
TI  - Simplified molecular diagnosis of fragile X syndrome by fluorescent methylation
      specific PCR and GeneScan analysis.
AB  - BACKGROUND: Fragile X syndrome (FXS), the most common cause of inherited mental
      impairment, is most commonly related to hyperexpansion and hypermethylation of a
      polymorphic CGG trinucleotide repeat in the 5' untranslated region of the FMR1
      gene. Southern blot analysis is the most commonly used method for molecular
      diagnosis of FXS. We describe a simplified strategy based on fluorescent
      methylation-specific PCR (ms-PCR) and GeneScan analysis for molecular diagnosis
      of fragile X syndrome. METHODS: We used sodium bisulfite treatment to selectively
      modify genomic DNA from fragile X and normal lymphoblastoid cell lines and from
      patients. We then performed ms-PCR amplification using fluorescently-labeled
      primers complementary to modified methylated or unmethylated DNA. Amplification
      products were resolved by capillary electrophoresis. FMR1 mutational status was
      determined by a combination of fluorescent peak sizes and patterns on the
      GeneScan electropherogram. RESULTS: DNA samples from male and female persons with
      known NL, PM, and FM FMR1 CGG repeats were analyzed. Each FMR1 genotype produced
      a unique GeneScan electropherogram pattern, thus providing a way to identify the
      various disease states. The number of CGG repeats in all NL and PM alleles were
      determined accurately. Analysis by both the new assay and Southern blot of a
      family segregating with FXS showed complete concordance between both methods.
      CONCLUSIONS: This simplified molecular diagnostic test, based on fluorescent
      methylation-specific PCR, may be a suitable alternative or complement to Southern
      blot analysis for the diagnosis of FXS.

PMID- 16793929
TI  - Genomic rearrangements at the BRCA1 locus in Spanish families with breast/ovarian
      cancer.
AB  - BACKGROUND: Large genomic rearrangements (LGRs) account for a substantial
      proportion of the BRCA1 disease-causing changes, or variations, identified in
      families with hereditary breast/ovarian cancer [HB(O)C]. Great differences in the
      spectrum and prevalence of BRCA1 LGR have been observed among populations. Here
      we report the first comprehensive analysis of BRCA1 LGRs conducted in Spain.
      METHODS: We used multiplex ligation-dependent probe amplification (MLPA) to
      screen for BRCA1 LGRs in the index case individuals of 384 HB(O)C families who
      previously tested negative for BRCA1 and BRCA2 point variations, small
      insertions, and deletions. An alternative set of MLPA probes, long-range PCR, and
      real-time PCR were used to confirm positive results. RESULTS: We have identified
      8 different BRCA1 rearrangements (del exon 1-24, del exon 8-13, del exon 11-15,
      del exon 14, dup exon 19-20, dup exon 20, exon 21-22 amplification, and del exon
      23-24). With the exception of del exon 8-13, they are novel alterations. Overall,
      BRCA1 LGRs explain 1.4% of the Spanish HB(O)C families, and they account for 8.2%
      of all BRCA1 pathogenic variations identified in our study population. BRCA1
      genetic variants affecting hybridization of commercially available MLPA probes
      are very rare in our population. CONCLUSIONS: Screening for BRCA1 LGRs should be
      mandatory in Spanish HB(O)C families. A high proportion of country-specific
      rearrangements are scattered along the gene. MLPA is a robust method to screen
      for LGRs in our population. MLPA analysis of positive samples with an alternative
      set of probes, together with long-range PCR and real-time PCR, is a feasible
      approach to confirm results in cases in which LGR breakpoints have not been
      characterized.

PMID- 16793930
TI  - Tumor necrosis factor-alpha -308G>A allelic variant modulates iron accumulation
      in patients with hereditary hemochromatosis.
AB  - BACKGROUND: In vitro and animal studies suggest that tumor necrosis factor alpha
      (TNF-alpha) modulates intestinal iron transport. We hypothesized that the effect
      of TNF-alpha might be particularly relevant if iron absorption is not effectively
      controlled by the HFE gene. METHODS: In patients with homozygous C282Y
      hemochromatosis, we investigated the influence of TNF-alpha -308G>A allelic
      variant on total body iron overload, determined in all patients by measuring iron
      removed during depletion therapy, and hepatic iron index and need for phlebotomy
      to prevent iron reaccumulation, measured in patient subgroups. RESULTS: Of 86
      patients with hereditary hemochromatosis, 16 (19%) were heterozygous carriers and
      1 (1%) was a homozygous carrier of the TNF-alpha promoter -308A allele. Mean (SD)
      total body iron overload was increased 2-fold in TNF-alpha -308A allele carriers
      [10.9 (7.6) g] compared with homozygous carriers of the G allele [5.6 (5.0) g,
      P<0.001]. Hepatic iron index differed markedly between TNF-alpha -308A allele
      carriers [5.6 (3.5) micromol/g/year] and homozygous G allele carriers [3.1 (2.2)
      micromol/g/year, P=0.040, n=30]. After iron depletion, the need for phlebotomy to
      prevent iron reaccumulation (maintenance therapy) was substantially higher in TNF
      alpha -308A allele carriers than in homozygous G allele carriers (P=0.014, n=73).
      We used multiple regression analyses to exclude possible confounding effects of
      sex, age, family screening, body-mass index, and meat or alcohol intake.
      CONCLUSION: TNF-alpha -308G>A allelic variant modulates iron accumulation in
      patients with hereditary (homozygous C282Y) hemochromatosis, but the effect of
      the TNF-alpha -308A allele on clinical manifestations of hemochromatosis was less
      accentuated than expected from the increased iron load associated with this
      allele.

PMID- 16793931
TI  - Calculation of bioavailable and free testosterone in men: a comparison of 5
      published algorithms.
AB  - BACKGROUND: Estimation of serum concentrations of free testosterone (FT) and
      bioavailable testosterone (bioT) by calculation is an inexpensive and
      uncomplicated method. We compared results obtained with 5 different algorithms.
      METHODS: We used 5 different published algorithms [described by Sodergard et al.
      (bioTS and FTS), Vermeulen et al. (bioTV and FTV), Emadi-Konjin et al. (bioTE),
      Morris et al. (bioTM), and Ly et al. (FTL)] to estimate bioT and FT
      concentrations in samples obtained from 399 independently living men (ages 40-80
      years) participating in a cross-sectional, single-center study. RESULTS: Mean
      bioT was highest for bioTS (10.4 nmol/L) and lowest for bioT(E) (3.87 nmol/L).
      Mean FT was highest for FTS (0.41 nmol/L), followed by FTV (0.35 nmol/L), and FTL
      (0.29 nmol/L). For bioT concentrations, the Pearson correlation coefficient was
      highest for the association between bioTS and bioTV (r = 0.98) and lowest between
      bioTM and bioTE (r = 0.66). FTL was significantly associated with both FTS (r =
      0.96) and FTV (r = 0.88). The Pearson correlation coefficient for the association
      between FTL and bioTM almost reached 1.0. Bland-Altman analysis showed large
      differences between the results of different algorithms. BioTM, bioTE, bioTV, and
      FTL were all significantly associated with sex hormone binding globulin (SHBG)
      concentrations. CONCLUSION: Algorithms to calculate FT and bioT must be
      revalidated in the local setting, otherwise over- or underestimation of FT and
      bioT concentrations can occur. Additionally, confounding of the results by SHBG
      concentrations may be introduced.

PMID- 16793932
TI  - Regulation of the expression of human organic anion transporter 3 by hepatocyte
      nuclear factor 1alpha/beta and DNA methylation.
AB  - Human organic anion transporter 3 (hOAT3/SLC22A8) is predominantly expressed in
      the proximal tubules of the kidney and plays a major role in the urinary
      excretion of a variety of organic anions. The promoter region of hOAT3 was
      characterized to elucidate the mechanism underlying the tissue-specific
      expression of hOAT3. The minimal promoter of hOAT3 was identified to be located
      approximately 300 base pairs upstream of the transcriptional start site, where
      there are canonical TATA and hepatocyte nuclear factor (HNF1) binding motifs,
      which are conserved in the rodent Oat3 genes. Transactivation assays revealed
      that HNF1alpha and HNF1beta markedly increased hOAT3 promoter activity, where the
      transactivation potency of HNF1beta was lower than that of HNF1alpha. Mutations
      in the HNF1 binding motif prevented the transactivation. Electrophoretic mobility
      shift assays demonstrated binding of the HNF1alpha/HNF1alpha homodimer or
      HNF1alpha/HNF1beta heterodimer to the hOAT3 promoter. It was also demonstrated
      that the promoter activity of hOAT3 is repressed by DNA methylation. Moreover,
      the expression of hOAT3 was activated de novo by forced expression of HNF1alpha
      alone or both HNF1alpha and HNF1beta together with the concomitant DNA
      demethylation in human embryonic kidney 293 cells that lack expression of
      endogenous HNF1alpha and HNF1beta, whereas forced expression of HNF1beta alone
      could not activate the expression of hOAT3. This suggests a synergistic action of
      the HNF1alpha/HNF1alpha homodimer or HNF1alpha/HNF1beta heterodimer and DNA
      demethylation for the constitutive expression of hOAT3. These results indicate
      that the tissue-specific expression of hOAT3 might be regulated by the concerted
      effect of genetic (HNF1alpha and HNF1beta) and epigenetic (DNA methylation)
      factors.

PMID- 16793933
TI  - Hyperhomocysteinemia increases arterial permeability and stiffness in mice.
AB  - We have reported that hyperhomocysteinemia (HHcy) evoked by folate depletion
      increases arterial permeability and stiffness in rats and that low folate without
      HHcy increases arterial permeability in mice. In this study, we hypothesized that
      HHcy independently increases arterial permeability and stiffness in mice.
      C57BL/6J mice that received rodent chow and water [control (Con), n=12] or water
      supplemented with 0.5% L-methionine (HHcy, n=12) for 18+/-3 wk had plasma
      homocysteine concentrations of 8+/-1 and 41+/-1 microM, respectively (P<0.05),
      and similar liver folate (approximately 12+/-2 microg folate/g liver). Carotid
      arterial permeability, assessed as dextran accumulation using quantitative
      fluorescence microscopy, was greater in HHcy (3.95+/-0.4 ng.min-1.cm-2) versus
      Con (2.87+/-0.41 ng.min-1.cm-2) mice (P<0.05). Stress versus strain curves
      generated using an elastigraph indicated that 1) maximal stress (N/mm2), 2)
      physiological stiffness (low-strain Young's modulus, mN/mm), and 3) maximal
      stiffness (high-strain Young's modulus, N/mm) were higher (P<0.05) in aortas from
      HHcy versus Con mice. Thus, chronic HHcy increases arterial permeability and
      stiffness. Carotid arterial permeability also was assessed in age-matched
      C57BL/6J mice before and after incubation with 1) xanthine (0.4 mg/ml)/xanthine
      oxidase (0.2 mg/ml; X/XO) to generate superoxide anion (O2-) or 50 microM DL
      homocysteine in the presence of 2) vehicle, 3) 300 microM diethylamine-NONOate
      (DEANO; a nitric oxide donor), or 4) 10(-3) M 4,5-dihydroxy-1,3-benzene
      disulfonic acid (tiron; a nonenzymatic intracellular O2- scavenger). Compared
      with preincubation values, X/XO and dl-homocysteine increased (P<0.05)
      permeability by 66+/-11% and 123+/-8%, respectively. DL-Homocysteine-induced
      increases in dextran accumulation were blunted (P<0.05) by simultaneous
      incubation with DEANO or tiron. Thus, acute HHcy increases arterial permeability
      by generating O2- to an extent whereby nitric oxide bioavailability is reduced.

PMID- 16793934
TI  - The sympathoinhibitory effects of systemic cholecystokinin are dependent on
      neurons in the caudal ventrolateral medulla in the rat.
AB  - The gastrointestinal hormone CCK inhibits a subset of presympathetic neurons in
      the rostroventrolateral medulla (RVLM) that may be responsible for driving the
      sympathetic vasomotor outflow to the gastrointestinal circulation. We tested the
      hypothesis that the central neurocircuitry of this novel sympathoinhibitory
      reflex involves a relay in the caudal ventrolateral medullary (CVLM) depressor
      area. Blood pressure and greater splanchnic sympathetic nerve discharge (SSND) or
      lumbar sympathetic nerve discharge (LSND) were monitored in anesthetised,
      paralyzed male Sprague-Dawley rats. The effects of phenylephrine (PE, 10
      microg/kg iv; baroreflex activation), phenylbiguanide (PBG, 10 microg/kg iv; von
      Bezold-Jarisch reflex) and CCK (4 or 8 microg/kg iv) on SSND or LSND, were tested
      before and after bilateral injection of 50-100 nl of the GABAA agonist muscimol
      (1.75 mM; n=6, SSND; n=7, LSND) or the excitatory amino acid antagonist
      kynurenate (55 mM; n=7, SSND) into the CVLM. PE and PBG elicited splanchnic and
      lumbar sympathoinhibitory responses that were abolished by bilateral muscimol or
      kynurenate injection into the CVLM. Similarly, the inhibitory effect of CCK on
      SSND was abolished after neuronal inhibition within the CVLM. In contrast, CCK
      evoked lumbar sympathoexcitation was accentuated following bilateral CVLM
      inhibition. In control experiments (n=7), these agents were injected outside the
      CVLM and had no effect on splanchnic sympathoinhibitory responses to PE, PBG, and
      CCK. In conclusion, neurons in the CVLM are necessary for the splanchnic but not
      lumbar sympathetic vasomotor reflex response to CCK. This strengthens the view
      that subpopulations of RVLM neurons supply sympathetic vasomotor outflow to
      specific vascular territories.

PMID- 16793936
TI  - Spontaneous, homeostatic, and inflammation-induced sleep in NF-kappaB p50
      knockout mice.
AB  - The dimeric transcription factor nuclear factor-kappaB (NF-kappaB) regulates
      several endogenous sleep-modulatory substances and thereby serves as a pivotal
      mediator of sleep-wake homeostasis. To further define the role of NF-kappaB in
      sleep regulation, we monitored sleep and temperature in mice that lack the p50
      subunit of NF-kappaB [p50 knockout (KO) mice]. Compared with the control
      B6129PF2/J strain, p50 KO mice spend more time in slow-wave sleep (SWS) and rapid
      eye movement sleep (REMS) under normal conditions and show enhanced homeostatic
      recovery of sleep after sleep loss. p50 KO mice also show increased SWS and
      reduced REMS and temperature after the administration of lipopolysaccharide, yet
      they are behaviorally less responsive to challenge with influenza virus. These
      data support a role for NF-kappaB, and, in particular, for the p50 subunit, in
      the regulation of sleep in healthy mice and in mice experiencing immune
      challenge.

PMID- 16793935
TI  - Deficiency of gammadelta T lymphocytes contributes to mortality and
      immunosuppression in sepsis.
AB  - Studies have indicated that gammadelta T lymphocytes play an important role in
      the regulation of immune function and the clearance of intracellular pathogens.
      We have recently reported that intraepithelial lymphocytes (IEL), which are rich
      in gammadelta T cells, within the small intestine illustrated a significant
      increase in apoptosis and immune dysfunction in mice subjected to sepsis.
      However, the contribution of gammadelta T cells to the host response to
      polymicrobial sepsis remains unclear. In this study, we initially observed that
      after sepsis induced by cecal ligation and puncture (CLP), there was an increase
      in small intestinal IEL CD8+gammadelta+ T cells in control gammadelta+/+ mice.
      Importantly, we subsequently found an increased early mortality in mice lacking
      gammadelta T cells (gammadelta-/- mice) after sepsis. This was associated with
      decreases in plasma TNF-alpha, IL-6, and IL-12 levels in gammadelta-/- mice
      compared with gammadelta+/+ mice after sepsis. In addition, even though in vitro
      LPS-stimulated peritoneal macrophages showed a reduction in IL-6 and IL-12
      release after CLP, these cytokines were less suppressed in macrophages isolated
      from gammadelta-/- mice. Alternatively, IL-10 release was not different between
      septic gammadelta+/+ and gammadelta-/- mice. Whereas T helper (Th)1 cytokine
      release by anti-CD3-stimulated splenocytes was significantly depressed in septic
      gammadelta+/+ mice, there was no such depression in gammadelta-/- mice. However,
      gammadelta T cell deficiency had no effect on Th2 cytokine release. These
      findings suggest that gammadelta T cells may play a critical role in regulating
      the host immune response and survival to sepsis, in part by alteration of the
      level of IEL CD8+gammadelta+ T cells and through the development of the Th1
      response.

PMID- 16793937
TI  - Quantification of cerebrospinal fluid transport across the cribriform plate into
      lymphatics in rats.
AB  - A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is
      transport through the cribriform plate in association with the olfactory nerves.
      CSF is then absorbed into lymphatics located in the submucosa of the olfactory
      epithelium (olfactory turbinates). In an attempt to provide a quantitative
      measure of this transport, 125I-human serum albumin (HSA) was injected into the
      lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20,
      30, 40, and 60 min after injection, and tissue samples, including blood (from
      heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised
      for radioactive assessment. The remains were frozen. To sample the olfactory
      turbinates, angled coronal tissue sections anterior to the cribriform plate were
      prepared from the frozen heads. The average concentration of 125I-HSA was higher
      in the middle olfactory turbinates than in any other tissue with peak
      concentrations achieved 30 min after injection. At this point, the recoveries of
      injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates,
      1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and
      0.09% tail. The current belief that arachnoid projections are responsible for CSF
      drainage fails to explain some important issues related to the pathogenesis of
      CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates
      further supports a role for lymphatics in CSF absorption and provides the basis
      of a method to investigate the novel concept that diseases associated with the
      CSF system may involve impaired lymphatic CSF transport.

PMID- 16793938
TI  - Exaggerated response to mild stress in rats fed high-fat diet.
AB  - It has been suggested that high-fat (HF) diet exaggerates the stress-induced
      release of glucocorticoids due to activation of the hypothalamic-pituitary
      adrenal (HPA) axis. In an initial experiment, in which rats were fed HF diet for
      4 days, we found that HF-fed controls stopped gaining weight, indicating that
      they were hyperresponsive to the mild stress of tail bleeding but responded the
      same as low-fat (LF)-fed rats to the more severe stress of restraint. A second
      experiment confirmed these results when rats fed a HF diet for 4 days showed an
      exaggerated corticosterone release in response to an intraperitoneal injection of
      saline and movement to a novel cage, compared with LF-fed rats. Experiment 3
      tested the same parameters as experiment 2 but interchanged the diets. This
      allowed us to differentiate between the effects of the dietary fat and the
      novelty of the diet. Additionally, this experiment determined whether
      hyperresponsiveness to mild stress in HF-fed rats was sustained during a
      prolonged exposure to diet. The results confirmed that a HF diet, not novelty,
      exaggerated the endocrine stress response after 9 days on the diet but that the
      effect was no longer present after 23 days on the diet. The hyperresponsiveness
      of the HPA axis in HF-fed rats is similar to that observed in animals that have
      been exposed to a significant chronic or acute stress, suggesting that the HF
      diet may initially be perceived as a stressor.

PMID- 16793939
TI  - Modeling baroreflex regulation of heart rate during orthostatic stress.
AB  - During orthostatic stress, arterial and cardiopulmonary baroreflexes play a key
      role in maintaining arterial pressure by regulating heart rate. This study
      presents a mathematical model that can predict the dynamics of heart rate
      regulation in response to postural change from sitting to standing. The model
      uses blood pressure measured in the finger as an input to model heart rate
      dynamics in response to changes in baroreceptor nerve firing rate, sympathetic
      and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations
      of norepinephrine and acetylcholine. We formulate an inverse least squares
      problem for parameter estimation and successfully demonstrate that our
      mathematical model can accurately predict heart rate dynamics observed in data
      obtained from healthy young, healthy elderly, and hypertensive elderly subjects.
      One of our key findings indicates that, to successfully validate our model
      against clinical data, it is necessary to include the vestibulo-sympathetic
      reflex. Furthermore, our model reveals that the transfer between the nerve firing
      and blood pressure is nonlinear and follows a hysteresis curve. In healthy young
      people, the hysteresis loop is wide, whereas, in healthy and hypertensive elderly
      people, the hysteresis loop shifts to higher blood pressure values, and its area
      is diminished. Finally, for hypertensive elderly people, the hysteresis loop is
      generally not closed, indicating that, during postural change from sitting to
      standing, baroreflex modulation does not return to steady state during the first
      minute of standing.

PMID- 16793940
TI  - Recurrent hypoglycemia reduces the glucose sensitivity of glucose-inhibited
      neurons in the ventromedial hypothalamus nucleus.
AB  - Recurrent hypoglycemia blunts the brain's ability to sense and respond to
      subsequent hypoglycemic episodes. Glucose-sensing neurons in the ventromedial
      hypothalamus nucleus (VMN) are well situated to play a role in hypoglycemia
      detection. VMN glucose-inhibited (GI) neurons, which decrease their firing rate
      as extracellular glucose increases, are extremely sensitive to decreased
      extracellular glucose. We hypothesize that recurrent hypoglycemia decreases the
      glucose sensitivity of VMN GI neurons. To test our hypothesis, 14- to 21-day-old
      Sprague-Dawley rats were subcutaneously injected with regular human insulin (4
      U/kg) or saline (control) for three consecutive days. Blood glucose levels 1 h
      after insulin injection on day 3 were significantly lower than on day 1,
      reflecting an impaired ability to counteract hypoglycemia. On day 4, the glucose
      sensitivity of VMN GI neurons was measured using conventional whole cell current
      clamp recording. After recurrent insulin-induced hypoglycemia, VMN GI neurons
      only responded to a glucose decrease from 2.5 to 0.1, but not 0.5, mM.
      Additionally, lactate supplementation also decreased glucose sensitivity of VMN
      GI neurons. Thus our findings suggest that decreases in glucose sensitivity of
      VMN GI neurons may contribute to the impairments in central glucose-sensing
      mechanisms after recurrent hypoglycemia.

PMID- 16793941
TI  - Downregulation in the expression of the serine dehydratase in the rat liver
      during chronic metabolic acidosis.
AB  - Blood pH controls the activity of important regulatory enzymes in the metabolism.
      Serine dehydratase (SerDH) transforms l-serine into pyruvate and ammonium and is
      involved in the regulation of gluconeogenesis from serine in the rat liver. In
      this work, we investigate the effect of chronic metabolic acidosis on the
      kinetics, specific protein level, tissue location, and mRNA levels of rat liver
      SerDH. Experimental acidosis was induced in rats by ingestion of 0.28 M ammonium
      chloride solution for 10 days. Acidosis significantly (P<0.05) decreased SerDH
      activity at all substrate concentrations assayed. Moreover, the Vmax value was
      38.50+/-3.51 mU/mg (n=7) of mitochondrial protein in the acidotic rats and
      92.49+/-6.79 mU/mg (n=7) in the control rats. Western blot analysis revealed a
      significant reduction (14%) in the level of SerDH protein content in the rat
      liver during acidosis. Immunohistochemical analysis showed that SerDH location
      did not change in response to chronic metabolic acidosis and confirmed previous
      results on SerDH protein levels. Moreover, the SerDH mRNA level, estimated by RT
      PCR, was also significantly 33.8% lower than in control. These results suggest
      that during experimental acidosis a specific repression of rat-liver SerDH gene
      transcription could result, lowering the amount and activity of this enzyme. The
      changes found in SerDH expression are part of an overall metabolic response of
      liver to maintain acid-base homeostasis during acidosis.

PMID- 16793942
TI  - Consensus statement on the standardisation of GH assays.

PMID- 16793943
TI  - Early textural and functional alterations of left ventricular myocardium in mild
      hypothyroidism.
AB  - The aim of the present study was to evaluate cardiac function and texture in
      patients with subclinical hypothyroidism (sHT) both by conventional and new
      ultrasonic intramyocardial tissue techniques. sHT was characterized by normal
      serum free tetraiodotironine and free triiodotironine levels and slightly
      increased serum TSH level. Twenty-four patients affected by sHT and 24 sex- and
      age-matched healthy volunteers were studied. All subjects were submitted to
      conventional two-dimensional (2D)-color Doppler echocardiography, pulsed wave
      tissue Doppler imaging (PWTDI) for the analysis of the diastolic function, color
      Doppler myocardial imaging (CDMI) for the analysis of regional strain and strain
      rate and integrated backscatter (IBS) for the evaluation of intrinsic
      contractility and tissue characterization. The results of the present study were:
      (a) the detection in sHT subjects of a lower cyclic variation index (CVI)
      indicating an altered myocardial intrinsic contractility; (b) a higher ultrasonic
      myocardial reflectivity indicating an altered myocardial texture; (c) the
      detection of lower systolic strain and strain-rate indicating an alteration of
      myocardial regional deformability; (d) an initial impairment of left ventricular
      diastolic function indicated by a decrease of peak E mitral flow velocity and an
      increase of peak A mitral flow velocity. All parameters studied with conventional
      2D-echo in sHT patients were comparable with controls, except for a mild
      alteration in diastolic function. A significant correlation among systo-diastolic
      modifications detected by CDMI and IBS and serum TSH levels were found. The CVI
      at septum, the PWDTI S-peak wave and the systolic strain at septum were inversely
      related to the serum TSH levels. In conclusion, the new intramyocardial
      ultrasonic techniques confirm and extend the previous knowledge on the effect of
      the sHT on the heart, allowing the detection of early ultrastructural and
      regional functional systolic and diastolic abnormalities.

PMID- 16793944
TI  - The effects of sex-steroid administration on the pituitary-thyroid axis in
      transsexuals.
AB  - OBJECTIVE: Estrogen and androgen administration modulate the pituitary-thyroid
      axis through alterations in thyroid hormone-binding globulin (TBG) metabolism,
      but the effects of sex steroids on extrathyroidal thyroxine (T4) to
      triiodothyronine (T3) conversion in humans are unknown. DESIGN AND METHODS: We
      studied 36 male-to-female and 14 female-to-male euthyroid transsexuals at
      baseline and after 4 months of hormonal treatment. Male-to-female transsexuals
      were treated with cyproterone acetate (CA) 100 mg/day alone (n = 10) or in
      combination with either oral ethinyl estradiol (or-EE) 100 microg/day (n = 14) or
      transdermal 17beta-estradiol (td-E) 100 microg twice a week (n = 12). Female-to
      male transsexuals were treated with i.m. testosterone 250 mg twice a week. A t
      test was used to test for differences within groups and ANOVA with post hoc
      analysis to test for differences between the groups. RESULTS: Or-EE increased TBG
      (100 +/- 12%, P < .001) and testosterone decreased TBG (-14 +/- 4%, P = 0.01),
      but free T4 did not change. Td-E and CA did not affect TBG concentrations. TSH
      was not different between groups at baseline or after treatment. CA decreased
      T3/T4 ratios (-9 +/- 3%, P = 0.04), suggesting that T4 to T3 conversion was
      lower. Testosterone increased T3/T4 ratios (30 +/- 9%, P = 0.02), which probably
      reflects higher T4 to T3 conversion. CONCLUSION: Oral but not transdermal
      estradiol increases TBG, whereas testosterone lowers TBG. Testosterone increases
      T3/T4 ratios. Estradiol does not affect T3/T4 ratios, irrespective of the route
      of administration.

PMID- 16793945
TI  - Perchlorate versus other environmental sodium/iodide symporter inhibitors:
      potential thyroid-related health effects.
AB  - OBJECTIVE: Perchlorate is a known competitive inhibitor of the sodium/iodide
      symporter (NIS). Possible thyroid-related effects of environmental perchlorate
      have created great health concerns, especially in the US, resulting in a debated
      reference dose (RfD) of 0.0007 mg/kg per day in drinking water recommended by the
      National Academy of Sciences (NAS). However, the impact of other environmental
      NIS inhibitors and the role of iodine seem to have received little attention in
      the whole debate. METHODS: We performed a PubMed search for articles published up
      to February 2006, using the key terms perchlorate, nitrate, thiocyanate, iodine,
      NIS, RfD, thyroid (alone or in combinations), with particular attention for human
      studies. In parallel, we critically analysed the January 2005 NAS' report,
      entitled 'Health implications of perchlorate ingestion'. RESULTS: The relative
      potencies of prevalent environmental NIS inhibitors (nitrate, thiocyanate and
      perchlorate) to inhibit iodine uptake have been estimated repeatedly with robust
      results. Our calculations show that nitrate and thiocyanate, acquired through
      drinking water or food, account for a much larger proportion of iodine uptake
      inhibition than perchlorate. Furthermore, the iodine uptake inhibitory effects of
      nitrate and thiocyanate - as defined by their legally accepted maximal
      contaminant levels in drinking water - exceed the potential effect of the
      proposed RfD for perchlorate by far. CONCLUSIONS: Iodine uptake inhibition and
      any potential downstream effect by perchlorate are highly dependent on the
      presence of other environmental NIS inhibitors and iodine intake itself. These
      potential confounders should therefore be considered in future studies and
      calculations for risk assessment.

PMID- 16793946
TI  - Thyroid nodule shape suggests malignancy.
AB  - OBJECTIVE: To evaluate if a nodule with shape taller than wide
      (anteroposterior/transverse diameter ratio, A/T > or = 1) is a good predictor of
      malignancy independent of the size. METHODS: We retrospectively examined the
      cytological and histological results of 7455 nodules (5198 patients) referred for
      ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from
      January 1991 to September 2004. RESULTS: A suitable FNAC was obtained from 6135
      nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules,
      SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious
      lesions after FNAC. The size of carcinoma nodules was not significantly
      associated with the occurrence of extracapsular growth (large nodules (LN):
      10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS).
      Malignant lesions showed microcalcifications more frequently than benign nodules
      (72.2 vs 28.7%; P < 0.001; (odds ratio, OR(confidence intervals, CI) = 9.9(7.2
      13.4)). Similarly, A/T > or = 1 (76 vs 40%; P < 0.001; OR(CI) = 8.6(5.5-13.1)),
      blurred margins (52.8 vs 18.8%; P < 0.001; OR(CI) = 7.7(5.6-10.2)), solid hypo
      echoic appearance (80.6 vs 52.4%; P < 0.001; OR(CI) = 3.2(2.2-4.3)) and
      intranodular vascular pattern (type 2) (61.6 vs 49.7%; P < 0.001; OR(CI) =
      1.7(1.3-2.3)) were significantly more frequent in malignant than in benign
      nodules. CONCLUSIONS: Our data show that no single parameter, including nodule
      size, satisfactorily identifies a subset of patients to be electively
      investigated by FNAC. We concluded that A/T > or = 1 with at least two of US
      features (microcalcification, blurred margins, hypo-echoic pattern) is today the
      best compromise between missing cancers and cost-benefit.

PMID- 16793947
TI  - Metabolic abnormalities in patients with normocalcemic hyperparathyroidism
      detected at a population-based screening.
AB  - OBJECTIVE: Dyslipidemia, hypertension, diabetes mellitus and also primary
      hyperparathyroidism (pHPT) are associated with an increased risk of
      cardiovascular diseases. Metabolic abnormalities in mild pHPT have been reported,
      but never in cases with normal calcium and high parathyroid hormone (PTH) levels,
      i.e. suffering from 'normocalcemic pHPT'. Our aim was to explore the occurrence
      of these metabolic abnormalities in individuals with normocalcemic pHPT
      identified in a population-based screening, and the effects of parathyroidectomy
      vs conservative treatment on metabolic variables. DESIGN AND METHODS: A
      population-based screening of 5202 post-menopausal women identified 30 patients
      with normal calcium, inappropriately high PTH and normal creatinine. A 5-year
      follow-up included 15 parathyroidectomized (PTx) and nine conservatively followed
      cases, in a non-randomized setting, together with age-matched controls.
      Biochemical variables and body mass index (BMI) were investigated. RESULTS: At
      study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein
      (LDL)/high-density lipoprotein (HDL)-cholesterol, very low-density lipoprotein
      (VLDL)-cholesterol, total triglycerides, and BMI compared to controls (P = <
      0.0001-0.035). The cases had a lower HDL-cholesterol value (P = 0.013) and one
      third of the cases had hypertriglyceridemia. During follow-up, the PTx cases
      decreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (P =
      0.0076-0.022). Investigated biochemical variables remained adverse in
      conservatively followed cases during follow-up except a decreased LDL-cholesterol
      value. All surgically treated patients had parathyroid adenoma. CONCLUSIONS:
      Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels,
      BMI and glucose levels compared to age-matched controls. Parathyroidectomy has
      positive effects on some of these variables and reverses them to the same level
      as the controls, while conservative treatment fails to normalize the investigated
      metabolic variables.

PMID- 16793948
TI  - The reduction of bone mineral density in postmenopausal women with primary
      hyperparathyroidism is higher in the presence of concomitant GH secretion
      impairment.
AB  - OBJECTIVE: To investigate, in a large group of postmenopausal primary
      hyperparathyroidism (PHP) women, whether the concomitance of GH deficiency (GHD)
      may contribute to the development of changes in bone mineral density (BMD).
      DESIGN: GH secretion, bone status and metabolism were investigated in 50
      postmenopausal women with PHP and in a control group of 60 women with no evidence
      of PHP, matched for age, age at menopause and body mass index (BMI). METHODS: GH
      response to growth hormone-releasing hormone (GHRH)+arginine (Arg), femoral neck
      BMD (g/cm2) by dual energy X-ray absorptiometry, BMI, serum-ionized calcium,
      parathyroid hormone (PTH) and markers of bone remodelling were evaluated in all
      patients and controls. RESULTS: Among PHP patients, GH secretion was reduced (8.8
      +/- 4.2 microg/l, range 1.1-16.5 microg/l) in 34 patients and normal (28.7 +/-
      11.8 microg/l, range 17.9-55.7 microg/l) in the remaining 16 (P < 0.05), no women
      in the control group had GHD (peak GH 33.8 +/- 10.9 microg/l, range 21.7 +/- 63.2
      microg/l). Osteoporosis (T-score < - 2.5) and osteopenia (T-score > -2.5 and < 
      1) were found in 73.5 and 17.6% of GHD patients, in 37.5 and 43.7% of patients
      with normal GH secretion and 3.1 and 27% of controls. T-score and BMD were not
      correlated with ionized calcium, age, age at menopause, BMI, GH peak and IGF-I
      but were correlated with serum PTH levels in both groups. T-score was correlated
      with serum levels of markers of bone remodelling only in PHP patients with GHD.
      CONCLUSIONS: Concomitant impairment of GH secretion may play a pathogenetic role
      in the occurrence of changes in bone mass observed in PHP and contribute to make
      them more severe.

PMID- 16793949
TI  - The spectrum of parathyroid gland dysfunction associated with the microdeletion
      22q11.
AB  - OBJECTIVE: Clinical features associated with microdeletion of chromosome 22q11
      (del(22)(q11)) are highly variable. Increased awareness of this condition is
      needed among specialists such as endocrinologists to reduce diagnostic delay and
      improve clinical care. The purpose of this study was to describe the phenotype of
      patients with del(22)(q11), focusing on parathyroid gland dysfunction. DESIGN AND
      METHODS: Charts of 19 patients, including one kindred of three, known to have
      del(22)(q11) diagnosed by fluorescence in situ hybridization (FISH) were reviewed
      from the register of the department of Medical Genetics. Major clinical features
      including hypoparathyroidism phenotype were collected. RESULTS: Parathyroid
      dysfunction was present in 8 out of 16 patients (50%). Six patients were
      diagnosed with overt hypoparathyroidism. Hypocalcemia manifested as laryngeal
      stridor within the first days of life (n = 3), seizures in infancy (n = 1) and
      adolescence (n = 2). The connection between hypoparathyroidism and diagnosis of
      del(22)(q11) was belated at the median age of 18 years. One patient had presented
      with transient neonatal hypoparathyroidism, and one patient had latent
      hypoparathyroidism. Within the kindred family, the phenotype variability
      including that of parathyroid dysfunction was as marked as between unrelated
      individuals. Standard karyotype failed to detect the deletion in 15 out of 19
      cases. CONCLUSIONS: Abnormal parathyroid function in the del(22)(q11) ranges from
      severe neonatal hypocalcemia to latent hypoparathyroidism. Del(22)(q11) should be
      considered as a potential cause of hypocalcemia even in young adult. When
      suspected, the diagnosis requires investigation by FISH. Furthermore, long-term
      calcemia follow-up is needed in normocalcemic patients with del(22)(q11) because
      of the possible evolution to hypocalcemic hypoparathyroidism.

PMID- 16793950
TI  - A gene-to-gene interaction between aromatase and estrogen receptors influences
      bone mineral density.
AB  - OBJECTIVE: The aromatization of androgenic precursors is the main source of
      estrogens in postmenopausal women. We tested the hypothesis that allelic variants
      of the genes coding for aromatase and estrogen receptors (ER) could interact to
      determine the estrogenic signals on the bone tissue and, consequently, bone
      mineral density (BMD). DESIGN: Cross-sectional study including 331 postmenopausal
      women. METHODS: BMD was measured by dual energy x-ray absorptiometry. A CG
      polymorphism of the aromatase gene as well as three polymorphisms of ERalpha (a
      TA repeat in the promoter region, a C T single nucleotide polymorphism (SNP) in
      intron 1 and an AG SNP in exon 8) and a CA repeat polymorphism of ERbeta were
      studied. RESULTS: Age, body weight and the aromatase genotype were associated
      with BMD. Allelic variants of ERbeta and the exon 8 of ERalpha did not show a
      significant association with BMD. The polymorphisms located on the promoter and
      intron 1 of ERalpha interacted strongly with aromatase. Thus, in women TT
      homozygous for the ERalpha gene, there was a marked influence of aromatase
      genotypes on BMD: spine BMD was 0.724 +/- 0.027 g/cm2 in women with CC aromatase
      alleles and 0.926 +/- 0.032 g/cm2 in those with GG alleles (P < 0.001). Hip BMD
      in women with CC and GG aromatase genotypes was 0.722 +/- 0.020 and 0.842 +/-
      0.026 g/cm2 respectively (P = 0.002). On the contrary, there were no aromatase
      related differences in BMD in women with CT/CC alleles of ERalpha. Similarly,
      aromatase-related differences in BMD were found in women with short alleles at
      the promoter region of ERalpha, but not in those with long alleles. Both ERalpha
      polymorphisms were in strong linkage disequilibrium (P < 0.001). CONCLUSION:
      These results suggest that the interaction between polymorphisms of genes
      involved in estrogen synthesis and estrogen signaling exerts an important
      influence on BMD in postmenopausal women, thus helping to explain, in part, its
      heritable component. Nevertheless, further studies are warranted to confirm this
      gene-to-gene interaction in other populations.

PMID- 16793951
TI  - Incidence of GH deficiency - a nationwide study.
AB  - OBJECTIVE: Data on incidence rates are scarce in GH deficiency (GHD). Here, we
      estimate the incidence rate in childhood onset (CO) and adult onset (AO) GHD in
      Denmark. DESIGN: We used three national registries to identify 9131 cases with an
      increased risk of GHD. Date of entry was defined using the date when a
      registration had taken place and when a date of sufficient information could be
      defined from a thorough examination of a record of a GHD patient, which ever came
      last. We considered date of entry as the incident date. METHODS: Sex-specific
      incidence rates of GHD in children and adults using the background population as
      reference. RESULTS: During 1980-1999, 1823 patients were incident. Three-hundred
      and three males and 191 females had CO, 744 males and 585 females had AO GHD. The
      incidence rate over time was stable for females with AO GHD and increasing for
      the other three subgroups. Average incidence rate for CO males, 2.58 (95%
      confidence interval (CI), 2.30-2.88), CO females, 1.70 (95% CI, 1.48-1.96), AO
      males, 1.90 (95% CI, 1.77-2.04), and AO females, 1.42 (95% CI, 1.31-1.54) all per
      100 000. The incidence rate was significantly higher in males compared to females
      in the CO GHD group (P < 0.001) and in the AO GHD group in the age ranges of 45
      64 and 65+years (P < 0.001). There was no significant difference in the 18-44
      years age group. CONCLUSIONS: In conclusion, we have identified the incidence
      rates of GHD in a nationwide study of Denmark. In this population-based study, we
      have identified in CO GHD and in the two oldest age groups of AO GHD, a
      statistically significant higher incidence rate in males when compared with
      females.

PMID- 16793952
TI  - Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose
      tolerance and insulin resistance in acromegaly.
AB  - OBJECT: Treatment with somatostatin analogues (SA) not only inhibits GH secretion
      but may also impair insulin secretion. In order to evaluate the influence of SA
      on glucose metabolism, we investigated insulin resistance (IR) and beta-cell
      function, using the recommended combination of homeostatic model assessment of IR
      (HOMA-IR) and beta-cell function (HOMA-beta). DESIGN AND METHODS: This is a
      prospective, cross-sectional study. We measured fasting insulin, blood glucose
      and IGF-I. Insulin and blood glucose measurements were taken 120 min after an
      oral glucose tolerance test with 75 g glucose. We studied 51 patients (27
      female/24 male, age 54 years (20-75)). Eighteen patients were on Lanreotide
      Autogel (LA) treatment, 33 had no medical treatment. GH-levels of more than 2.5
      ng/ml was reached by 59% of the patients, 74.5% had normal IGF-I levels. RESULTS:
      We found no significant influence of disease activity on HOMA-IR and HOMA-beta.
      In the 33 of 51 subjects without any drug treatment, median HOMA-beta was 170.4%
      (36.0-624.0%). In contrast, in the 18 patients on LA treatment, median HOMA-beta
      was found to be significantly lower (84.2% (36.5-346.2%); P = 0.001). Despite
      this, there was no difference in HOMA-IR in both groups (2.4 (0.7-8.4) vs 2.3
      (0.7-6.1); P < 0.001) despite similar insulin values. CONCLUSION: In conclusion,
      we found that LA decreases beta-cell function significantly without affecting IR.
      Therefore, we think that insulin secretagogues are probably more effective in the
      treatment of diabetes mellitus in acromegalic patients on LA therapy than insulin
      sensitizers.

PMID- 16793953
TI  - Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults - a
      KIMS database analysis.
AB  - OBJECTIVE: The aim of the present study was to clarify the relationship between
      GH deficiency (GHD) and some cardiovascular risk factors and to analyse the
      effect of GH replacement therapy in a large number of patients over a prolonged
      period of time. DESIGN: Data for analysis were retrieved from KIMS (Pfizer
      International Metabolic Database). Serum concentrations of total cholesterol,
      high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)
      cholesterol and triglycerides were obtained from 2589 patients at baseline and
      from 1206 patients after 1 and 2 years of GH replacement therapy. Body mass index
      (BMI), waist and hip, resting blood pressure and body composition were also
      measured. RESULTS: At baseline, the unfavourable effects of GHD were most obvious
      in the lipid profile demonstrating elevated mean total and LDL-cholesterol, in
      the increased waist circumference and the elevated BMI. The cholesterol
      concentration, BMI and body composition were significantly adversely affected by
      a number of factors, including age, sex and the use of anti-epileptic drugs. The
      therapeutic effect of GH was essentially uniform across the whole population. GH
      replacement reduced significantly the mean total and LDL-cholesterol, the waist
      circumference and the fat mass and was maintained during 2 years. CONCLUSIONS:
      This analysis of a large number of patients confirmed that GHD adults present
      with an increased cardiovascular risk. The sustained improvement of the adverse
      lipid profile and body composition suggests that GH replacement therapy may
      reduce the risk of cardiovascular disease and the premature mortality seen in
      hypopituitary patients with untreated GHD.

PMID- 16793954
TI  - GH secretory pattern in young adults who discontinued GH treatment for GH
      deficiency and decreased longitudinal growth in childhood.
AB  - OBJECTIVE: Some adolescents who discontinue GH treatment due to GH deficiency
      (GHD) and short stature in childhood do not have classical GHD at retesting in
      adult life. It is unknown whether there is a neuroendocrine disturbance in the
      spontaneous pattern of GH release in these patients. DESIGN/PATIENTS/METHODS:
      Thirty-seven adolescents, who had received treatment with GH due to impaired
      longitudinal growth, were included. The adolescents were divided into two groups;
      one (GHD; n = 19) with classical GHD in adult life and another (GH sufficient
      (GHS); n = 18) without classical adult GHD. One year after GH discontinuation, 24
      h GH profiles were performed with blood sampling every 30 min. Sixteen matched
      healthy controls were also studied. All blood samples were analysed using an
      ultrasensitive GH assay and then, approximate entropy (ApEn) and deconvolution
      analysis were performed. RESULTS: The GHD group had higher mean ApEn level than
      the healthy controls (P < 0.05). As measured by deconvolution analysis, they had
      lower basal GH secretion (P < 0.01), increased number of GH peaks (P < 0.001),
      but lower burst mass (P < 0.001), lower percentage pulsatile GH secretion (P <
      0.001) and lower total GH secretion (P < 0.001), compared with control subjects.
      Adolescents in the GHS group had a pattern of 24-h GH release similar to that in
      healthy controls. CONCLUSION: Young adults with childhood-onset severe GHD have a
      high-frequency, low-amplitude GH secretion with decreased orderliness. The
      adolescents without classical GHD in adult life maintain a pattern of spontaneous
      GH release that is not statistically different from that in the healthy controls.

PMID- 16793955
TI  - Primary hypophysitis: clinical-pathological correlations.
AB  - OBJECTIVE: Primary hypophysitis comprises of three distinct histomorphological
      entities: lymphocytic, granulomatous and xanthomatous. Clinical features of the
      three subtypes for diagnostic and treatment strategies have yet not been well
      characterized. METHODS: Endocrine function, visual fields and acuity as well as
      magnetic resonance imaging characteristics were assessed before and after
      transphenoidal surgery in the largest series of 31 patients with primary
      hypophysitis (21 lymphocytic, 6 granulomatous, and 4 xanthomatous cases).
      RESULTS: Only lymphocytic hypophysitis occurred during pregnancy (30%) and was
      associated with other autoimmune diseases (24%). Visual fields and acuity
      abnormalities were not seen in xanthomatous hypophysitis. Lymphocytic and
      granulomatous hypophysitis most often resulted in severe dysfunction of the
      adrenal, gonadal and thyroidal axes as well as diabetes insipidus. For patients
      presenting with xanthomatous hypophysitis most often, mild anterior pituitary
      axis failure was documented and posterior pituitary involvement was hardly found.
      The outcome after transphenoidal biopsy was generally favorable. Pre- or
      postsurgical glucocorticoid treatment was very effective in 75% of the
      lymphocytic form in reducing the pituitary size. In contrast, glucocorticoid
      therapy was less effective in granulomatous or xanthomatous hypophysitis.
      CONCLUSION: Diffuse destruction of the complete pituitary gland including the
      infundibulum has to be considered in lymphocytic and granulomatous hypophysitis,
      whereas in xanthomatous, a circumscribed anterior pituitary lesion leading to
      compression of the pituitary gland without alteration of the pituitary stalk and
      optic chiasm can be assumed.

PMID- 16793956
TI  - Does long-term GH replacement therapy in hypopituitary adults with GH deficiency
      normalise quality of life?
AB  - OBJECTIVE: To determine whether impaired quality of life (QoL) in adults with GH
      deficiency (GHD) is reversible with long-term GH therapy and whether the
      responses in QoL dimensions differ from each other. METHODS: QoL was measured by
      the Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL
      AGHDA) in general population samples in England & Wales, The Netherlands, Spain
      and Sweden (n = 892, 1038, 868 and 1682 respectively) and compared with
      corresponding patients' data from KIMS (Pfizer International Metabolic Database)
      (n = 758, 247, 197 and 484 respectively) for 4-6 years a follow-up. The subsets
      of patients from England and Wales, and Sweden with longitudinal data for 5
      years' follow-up were also analysed. The change of the total QoL-AGHDA scores and
      responses within dimensions were evaluated. Subanalyses were performed to
      identify any specificity in response pattern for gender, age, disease-onset and
      aetiology. RESULTS: Irrespective of the degree of impairment, overall QoL
      improved dramatically in the first 12 months, with steady progress thereafter
      towards the country-specific population mean. Problems with memory and tiredness
      were the most serious burden for untreated patients, followed by tenseness, self
      confidence and problems with socialising. With treatment, these improved in the
      reverse order, normalising for the latter three. CONCLUSIONS: Long-term GH
      replacement results in sustained improvements towards the normative country
      specific values in overall QoL and in most impaired dimensions. The lasting
      improvement and almost identical pattern of response in each patient subgroup and
      independent of the level of QoL impairment support the hypothesis that GHD may
      cause these patients' psychological problems.

PMID- 16793957
TI  - Phenotypic variation in constitutional delay of growth and puberty: relationship
      to specific leptin and leptin receptor gene polymorphisms.
AB  - OBJECTIVES: Constitutional delay of growth and puberty (CDGP) is a variant of
      normal pubertal timing and progress, often with dominant inheritance. It is
      likely that one or more genes will be associated with CDGP. Possible candidates
      are the leptin (L) and the leptin receptor (LR) genes, as the leptin axis links
      nutritional status to pubertal development. This study has assessed whether a) L
      or LR gene polymorphisms were associated with CDGP and b) the CDGP phenotype was
      influenced by these polymorphisms. DESIGN: Case-control and transmission
      disequilibrium tests were used to test genetic association of L and LR
      polymorphisms with CDGP. METHODS: We genotyped L (3'CTTT repeat) and LR
      polymorphisms (Gln > Arg substitution, exon 6) in 81 CDGP children and 94
      controls in the UK and 88 CDGP children from the US and assessed the effect of
      genotype on their anthropometric characteristics. RESULTS: There was no
      association of these L or LR gene polymorphisms with CDGP. There was no
      difference in height or bone age delay within L or LR genotypes. However, UK CDGP
      children homozygous for the L short allele were heavier than heterozygotes and
      long allele homozygotes, with a similar trend in the US cohort. UK CDGP children
      with severe pubertal delay, who were thin, had significantly greater bone age
      delay and an increased frequency of parental pubertal delay than other groups and
      were less likely to be L short allele homozygotes. CONCLUSIONS: There was no
      association of specific L or LR polymorphisms with CDGP, but L short allele
      carriage influenced the phenotype within CDGP.

PMID- 16793958
TI  - The androgen receptor CAG repeat modifies the impact of testosterone on insulin
      resistance in women with polycystic ovary syndrome.
AB  - OBJECTIVE: Hyperandrogenism is a central feature of the polycystic ovary syndrome
      (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act
      through the androgen receptor (AR). A polymorphic CAG repeat sequence within the
      AR gene was reported to modulate its transactivation activity. Therefore, we
      investigated a putative interaction between testosterone and the CAG repeat
      length polymorphism with respect to IR. DESIGN: In 63 PCOS women with normal
      glucose tolerance free testosterone, the biallelic CAG repeat length and a
      multiplicative interaction term were investigated by multiple linear regression
      analysis for an association with IR as indicated by the homeostasis model
      assessment of IR (HOMA-IR). RESULTS: Free testosterone was correlated with HOMA
      IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as
      indicated by an interaction term. This interaction remained significant after
      adjustment for smoking, age and body mass index. While there was a positive
      association of free testosterone with HOMA-IR, the interaction term was inversely
      associated. The model, which explained 42.5% of the variation of HOMA-IR
      predicted that in carriers of short CAG lengths, an increase in testosterone
      increased IR. This effect attenuated with rising biallelic CAG length until it
      turns into the opposite at a CAG length longer than 23. The results were
      confirmed by using CIGMA as another measure of IR. CONCLUSIONS: The association
      between testosterone and IR is modified by the CAG repeat polymorphism within the
      AR. Therefore, the evaluation of testosterone effects on IR seems to require
      consideration of the AR CAG repeat polymorphism in PCOS women.

PMID- 16793959
TI  - Oxidised low-density lipoprotein concentration - early marker of an altered lipid
      metabolism in young women with PCOS.
AB  - OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are assumed to be at
      increased risk for cardiovascular diseases. This study examined the variations in
      oxidised low-density lipoprotein (OxLDL) concentration in relation to insulin
      levels in young women with PCOS. DESIGN: Cross-sectional clinical study in
      tertiary cares research hospitals. A total of 179 women with PCOS (79 overweight)
      and 56 age- and body mass index-matched controls were examined. METHODS: Blood
      samples were collected in follicular phase of the cycle for the basal glucose,
      total-, high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol, OxLDL,
      triglycerides, apolipoprotein-A1 (Apo-A1) and B (Apo-B), lipoprotein (a),
      insulin, testosterone and sex hormone-binding globulin (SHBG). Homeostatic model
      index (HOMA) and free androgen index (FAI) were determined. RESULTS: Overweight
      and normal weight women with PCOS had higher concentrations of OxLDL than their
      control counterparts (P = 0.007 and 0.003 respectively). Both the basal insulin
      (P = 0.003) and HOMA values (P < 0.001) were significantly higher in overweight
      than normal weight patients. Testosterone and FAI were higher in patients than in
      the respective controls (P < 0.001). The only independent predictor of increased
      OxLDL concentration in normal weight patients was Apo-B-to-Apo-A1 ratio (P <
      0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 2.3-16.4), while in
      obese PCOS, it was total cholesterol-to-high-density lipoprotein cholesterol
      ratio (P < 0.001, OR 2.8; 95% CI 1.6-4.9). CONCLUSION: Young normal weight and
      overweight PCOS women have similarly increased OxLDL levels. Our results may
      indicate the presence of primary alteration in lipid metabolism in patients with
      PCOS. To answer the question whether the alteration in LDL particle size can by
      itself pose a higher cardiovascular risk, a careful follow-up of these women is
      needed.

PMID- 16793960
TI  - Serum leptin and C-reactive protein levels in the physiological spontaneous
      menstrual cycle in reproductive age women.
AB  - OBJECTIVE: Only a few studies have investigated variations of different markers
      for inflammatory processes during the physiological menstrual cycle. The results
      are conflicting, particularly concerning the correlation between the marker
      leptin and steroid hormones. The aim of the study was to investigate the
      inflammatory markers C-reactive protein (CRP) and leptin in the serum of healthy,
      normally ovulating women and to correlate these with each other and with the
      hormones of the gonadal axis. A cycle-dependence of the markers studied would
      imply an exact timing of the blood sampling for clinical needs. DESIGN:
      Observational study investigating the two inflammatory markers CRP and leptin in
      relation to the hormonal pattern of the gonadal axis during the normal cycle.
      METHODS: Ovulatory cycles of 36 healthy, young, normo-androgenic women, having a
      normal body mass index were evaluated. Serum concentrations of leptin and CRP, as
      well as of follicle-stimulating hormone, luteinising hormone, 17beta-oestradiol,
      progesterone, prolactin (PRL) and free testosterone were measured every 1-2 days
      during one full cycle. RESULTS: Serum levels of leptin and CRP behaved
      differently during ovulatory cycles, with higher concentrations for leptin only
      during certain phases. Significant correlations were found in the follicular
      phase between leptin and PRL and leptin and free testosterone. CONCLUSIONS:
      Leptin levels change during the menstrual cycle. Leptin levels are more stable on
      cycle days 1-5 than later in the cycle. For precise cycle-independent
      measurements, these fluctuations have to be taken into account. There is no
      similar cyclic pattern for CRP.

PMID- 16793961
TI  - Clinical and biochemical description of a novel CYP21A2 gene mutation 962_963insA
      using a new 3D model for the P450c21 protein.
AB  - OBJECTIVE: A severely virilized 46, XX newborn girl was referred to our center
      for evaluation and treatment of congenital adrenal hyperplasia (CAH) because of
      highly elevated 17alpha-hydroxyprogesterone levels at newborn screening;
      biochemical tests confirmed the diagnosis of salt-wasting CAH. Genetic analysis
      revealed that the girl was compound heterozygote for a previously reported Q318X
      mutation in exon 8 and a novel insertion of an adenine between nucleotides 962
      and 963 in exon 4 of the CYP21A2 gene. This 962_963insA mutation created a
      frameshift leading to a stop codon at amino acid 161 of the P450c21 protein. AIM
      AND METHODS: To better understand structure-function relationships of mutant
      P450c21 proteins, we performed multiple sequence alignments of P450c21 with three
      mammalian P450s (P450 2C8, 2C9 and 2B4) with known structures as well as with
      human P450c17. Comparative molecular modeling of human P450c21 was then performed
      by MODELLER using the X-ray crystal structure of rabbit P450 2B4 as a template.
      RESULTS: The new three dimensional model of human P450c21 and the sequence
      alignment were found to be helpful in predicting the role of various amino acids
      in P450c21, especially those involved in heme binding and interaction with P450
      oxidoreductase, the obligate electron donor. CONCLUSION: Our model will help in
      analyzing the genotype-phenotype relationship of P450c21 mutations which have not
      been tested for their functional activity in an in vitro assay.

PMID- 16793962
TI  - Hypothalamic-pituitary-adrenal axis activity in adults who were prenatally
      exposed to the Dutch famine.
AB  - OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be
      susceptible to fetal programming, the process by which an adverse fetal
      environment elicits permanent physiological and metabolic alterations
      predisposing to disease in later life. It is hypothesized that fetal exposure to
      poor circumstances alters the set point of the HPA axis, leading to increased HPA
      axis activity and subsequent increased cortisol concentrations. In this study, we
      tested the hypothesis that prenatal exposure to famine during different periods
      of gestation is associated with increased activity of the HPA axis. DESIGN AND
      METHODS: We assessed plasma cortisol concentrations after a dexamethasone
      suppression and an ACTH1-24 -stimulation test in a group of 98 men and women
      randomly sampled from the Dutch famine birth cohort. Cohort members were born as
      term singletons around the 1944-1945 Dutch famine. RESULTS: Cortisol profiles
      after dexamethasone suppression and ACTH1-24 stimulation were similar for
      participants exposed to famine during late, mid- or early gestation (P = 0.78).
      Cortisol concentrations after dexamethasone suppression test did not differ
      between those exposed and those unexposed to famine in utero (mean difference -2%
      (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration
      (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47))
      or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 to 12))
      differed between exposed and unexposed participants. CONCLUSIONS: Prenatal famine
      exposure does not seem to affect HPA axis activity at adult age, at least not at
      the adrenal level. This does not exclude altered HPA axis activity at the levels
      of the hippocampus and hypothalamus.

PMID- 16793963
TI  - Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose
      tolerant obese subjects during weight loss.
AB  - OBJECTIVE: To investigate the mRNA expression of adiponectin, AdipoR1 and
      AdipoR2, the two recently cloned adiponectin receptors and peroxisome
      proliferator activated receptor (PPAR)gamma2 in adipose tissue of obese
      individuals before and during a very low calorie diet (VLCD) inducing weight
      loss. METHODS: Twenty-three non-diabetic obese subjects with normal (NGT, n = 11)
      or impaired glucose tolerance (IGT, n = 12) (age, 47 +/- 3 years; body mass
      index, 39.3 +/- 1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet
      daily without exercise. mRNA levels of nine IGT and six NGT subjects were
      measured by real-time PCR in s.c. abdominal adipose tissue. RESULTS: Metabolic
      parameters and insulin sensitivity were improved by VLCD in the IGT group, but
      minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the
      IGT (P = 0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARgamma2
      mRNA levels did not change during VLCD in any group. In the IGT, but not in the
      NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of
      PPARgamma2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively
      related to each other and to that of adiponectin. CONCLUSION: In the NGT group,
      the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin
      sensitivity and the expression of the adiponectin system in adipose tissue. By
      contrast, in the IGT group, AdipoR1 expression increased and we found a
      coordinate regulation of the expression of adiponectin and its receptors. These
      modifications could participate, through adiponectin action on adipocytes, to the
      improved metabolic parameters observed in IGT subjects.

PMID- 16793964
TI  - Serum adiponectin and leptin levels in relation to the metabolic syndrome,
      androgenic profile and somatotropic axis in healthy non-diabetic elderly men.
AB  - OBJECTIVE: The relationships between adipocytokines, sex steroids and the GH/IGF
      I axis is poorly studied and subject to controversy in healthy elderly male
      subjects. We investigated the association between both adiponectin and leptin,
      and the metabolic syndrome (MetS), lipid parameters, insulin sensitivity, sex
      steroids and IGF-I in healthy non-diabetic Lebanese men. DESIGN AND METHODS: In
      this cross-sectional study, a total of 153 healthy non-diabetic men aged 50 and
      above (mean age 59.3 +/- 7 years) had a detailed clinical and biological
      evaluation. Subjects were classified according to the National Cholesterol
      Education Program criteria of the MetS. Insulin sensitivity was determined by the
      Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: Subjects with the
      MetS had lower adiponectin and higher leptin levels (P < 0.0001 for both
      variables) compared with individuals without the MetS. Adiponectin was
      significantly correlated with waist size, triglycerides, high-density lipoprotein
      (HDL) cholesterol and QUICKI (r = -0.33, -0.26, 0.45 and 0.36 respectively, P <
      0.0001 for all variables). The relation between adiponectin and HDL cholesterol,
      triglycerides and QUICKI remained significant after adjustment for age and body
      mass index (BMI). Also, leptin was strongly correlated with waist size and QUICKI
      (r = 0.63 and -0.63 respectively, P < 0.001 for both variables). However, its
      relation to the lipid profile was weak (for cholesterol r = 0.16, P < 0.05; for
      triglycerides r = 0.17, P < 0.05) and disappeared after adjustment for BMI.
      Adiponectin was positively correlated with sex hormone-binding globulin (SHBG) (r
      = 0.39, P < 0.001) and inversely correlated with free-androgen index (r = -0.24,
      P < 0.01), estradiol and dehydroepiandrosterone sulfate (r = -0.165, P < 0.05; r
      = -0.21, P < 0.01 respectively). This difference remained significant for SHBG
      after adjustment for age and BMI (r = 0.20, P < 0.005). Finally, leptin was
      inversely correlated with total testosterone and SHBG (r = -0.44, P < 0.001; r = 
      0.30, P < 0.001 respectively); the relation with testosterone remained
      significant after adjustment for BMI. No significant relationship of either
      adiponectin or leptin with GH or IGF-I values was observed. In a stepwise
      multiple regression analysis, the independent predictors of adiponectin were HDL
      cholesterol, QUICKI, age and BMI (P < 0.0001, P = 0.005, P = 0.002 and P = 0.047
      respectively) while for leptin, it was QUICKI, waist size and testosterone (P <
      0.0001, P < 0.0001 and P = 0.004 respectively). The adjusted R2 values were 0.34
      and 0.55. CONCLUSION: Our results show that in a healthy elderly male population,
      both adiponectin and leptin are related to insulin sensitivity, independent of
      age and BMI. While adiponectin is independently related to triglycerides and HDL
      cholesterol, the weak relationship of leptin to the lipid profile is completely
      mediated by BMI. In addition, and more interestingly, both adipocytokines are
      strongly associated with sex steroids. We speculate that SHBG is regulated by
      adiponectin and that there is an inhibitory effect of testosterone on the
      adiponectin gene. Further studies are needed to fully elucidate these
      relationships.

PMID- 16793965
TI  - Expression of adrenomedullin in adipose tissue of lean and obese women.
AB  - OBJECTIVE: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide,
      was shown recently to be expressed by adipose tissue. The aim of our study was to
      investigate the precise localization of AM within human adipose tissue, and to
      examine AM regulation in obesity. DESIGN: Subcutaneous (SC) and omental (OM)
      adipose tissues from 9 lean and 13 obese women were profiled for AM expression
      changes. Preadipocytes from human adipose tissue were isolated and differentiated
      under defined adipogenic conditions. METHODS: AM expression was analyzed by
      immunohistochemistry, in situ hybridization and quantitative RT-PCR. RESULTS: A
      strong AM expression was observed in vessel walls, stromal cell clusters and
      isolated stromal cells, some of them being CD 68 positive, whereas mature
      adipocytes were not labeled. Calcitonin receptor-like receptor and receptor
      activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls.
      In vitro, preadipocytes of early differentiation stages spontaneously secreted
      AM. No difference in AM localization was found between SC and OM adipose tissue.
      AM levels in SC tissue did not differ between lean and obese subjects. By
      contrast, AM levels in OM tissue were significantly higher in obese as compared
      with lean women. Moreover, we found a positive relationship between OM AM and
      tumor necrosis factor alpha mRNA levels and AM-immunoreactive area in OM tissue
      followed the features of the metabolic syndrome. CONCLUSION: Stromal cells from
      human adipose tissue, including macrophages, produce AM. Its synthesis increased
      in the OM territory during obesity and paralleled the features of the metabolic
      syndrome. Therefore, AM should be considered as a new member of the adipokine
      family.

PMID- 16793967
TI  - Assessing 1-h plasma glucose and shape of the glucose curve during oral glucose
      tolerance test.
AB  - OBJECTIVE: To assess the cutoff values at different time points for impaired
      glucose regulation (IGR) and diabetes, the glucose curve and isolated 1-h
      hyperglycemia were monitored during an oral glucose tolerance test (OGTT).
      METHODS: Two thousand eight hundred and eighty-six subjects (1300 men and 1586
      women) were recruited to have an OGTT. Plasma was collected at 0, 30, 60, 120,
      and 180 min to analyze glucose and insulin. The diagnosis of impaired fasting
      glucose, impaired glucose tolerance, and diabetes was based on World Health
      Organization and American Diabetes Association's criteria. Those with fasting
      plasma glucose (FPG) < 5.6 and 2-h plasma glucose (PG) < 7.8, but 1-h PG > or =
      7.8 and < 11.1 mmol/l were defined as 1h-High7.8, and those with FPG < 7.0 and 2
      h PG < 11.1, but 1-h PG > or =11.1 mmol/l as 1h-High11.1. The cutoff values were
      calculated by receiver operating characteristic (ROC) curve. The correlation
      between beta-cell function and the area under the curve of glucose (AUCg) and the
      shape index was analyzed with linear regression. RESULTS: The cutoff values for
      IGR were 5.6, 9.7, 10.1, 7.8 and 6.1 mmol/l for blood glucose at 0, 30, 60, 120
      and 180 min, 24 for AUCg and 1.3 mmol/l for the shape index. The cutoff values
      for diabetes were 6.8, 11.2, 13, 11.1 and 7 mmol/l for 0, 30, 60, 120 and 180
      min, 30.9 for AUCg and 2 mmol/l for the shape index. Both AUCg and the shape
      index were inversely related to beta-cell function. The profiles of glucose and
      insulin in the subgroup with isolated 1-h hyperglycemia were very different from
      those seen in subjects with normal glucose tolerance or IGR. CONCLUSIONS: The
      present study provides new information on measures other than the fasting and 2-h
      PG to evaluate glucose metabolism in vivo and stimulates further research aimed
      at assessing the value of the OGTT 1-h PG concentration prospectively.

PMID- 16793966
TI  - Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal
      dysfunction in type 2 diabetic nephropathy.
AB  - OBJECTIVE: Ghrelin is a novel peptide hormone, which exerts somatotropic,
      orexigenic and adipogenic effects. Recent studies have shown that the
      preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr)
      concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as
      compared with the 72Met non-carriers. We hypothesized that the preproghrelin
      Leu72Met polymorphism is associated with a lower rate of developing renal
      dysfunction in patients with type 2 diabetic nephropathy. DESIGN: The
      preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138
      patients with diabetic nephropathy divided into two groups, one with normal renal
      function and the other with renal dysfunction. METHODS: Determination of the
      frequency of the preproghrelin Leu72Met polymorphism was the main outcome
      measure. RESULTS: The frequency of the Leu72Met polymorphism in diabetic
      nephropathy was significantly lower in patients with renal dysfunction (15.9%, P
      < 0.01) than in patients with normal renal function (42.0%) or in the diabetes
      control group (40.6%). The Leu72Met polymorphism was also associated with serum
      total cholesterol levels in diabetic nephropathy patients with renal dysfunction;
      the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers
      (P < 0.05). CONCLUSION: These data suggest that 72Met carrier status may be used
      as a marker predicting a lower chance of developing renal dysfunction in diabetic
      nephropathy.

PMID- 16793969
TI  - Science to practice: Will improved assessment of response to antiangiogenic
      therapies be achieved with contrast-enhanced gray-scale US?
AB  - McCarville et al have used gray-scale contrast-enhanced low-mechanical-index, and
      thus non-bubble-destructive, continuous US to quantitate tumor blood flow in
      mouse tumors engineered to simulate antiangiogenic therapy. They have shown that
      contrast-enhanced gray-scale US, unlike power or color Doppler US performed
      without contrast enhancement, is better able to depict and distinguish
      microvascular flow in subcutaneously implanted mouse tumors possessing different
      vascular phenotypes.

PMID- 16793970
TI  - Mammography: better, safer, and more effective?

PMID- 16793971
TI  - Diagnostic performance of stress perfusion and delayed-enhancement MR imaging in
      patients with coronary artery disease.
AB  - PURPOSE: To prospectively determine the accuracy of a combined magnetic resonance
      (MR) imaging approach (stress first-pass perfusion imaging followed by delayed
      enhancement imaging) for depicting clinically significant coronary artery
      stenosis (> or = 70% stenosis) in patients suspected of having or known to have
      coronary artery disease (CAD), with coronary angiography serving as the reference
      standard. MATERIALS AND METHODS: The committee on human research approved the
      study protocol, and all participants gave written informed consent. This study
      was HIPAA compliant. Forty-seven patients (38 men and nine women; mean age, 63
      years +/- 5.3 [standard deviation]) scheduled for coronary angiography were
      prospectively enrolled: 33 were suspected of having CAD (group A) and 14 had
      experienced a previous myocardial infarction and were suspected of having new
      lesions (group B). The MR imaging protocol included cine function, gadolinium
      enhanced stress and rest first-pass perfusion MR imaging, and delayed-enhancement
      MR imaging. Myocardial ischemia was defined as a segment with perfusion deficit
      at stress first-pass perfusion MR imaging and no hyperenhancement at delayed
      enhancement imaging. Myocardial infarction was defined as an area with
      hyperenhancement at delayed-enhancement imaging. RESULTS: One patient was
      excluded from analysis because of poor-quality MR images. Coronary angiography
      depicted significant stenosis in 30 of 46 patients (65%). In a per-vessel
      analysis (n = 138), stress first-pass perfusion MR imaging and delayed
      enhancement imaging yielded sensitivity of 0.87, specificity of 0.89, and
      accuracy of 0.88, when compared with coronary angiography. The diagnostic
      accuracy of stress first-pass perfusion MR imaging and delayed-enhancement
      imaging was slightly better than that of stress and rest first-pass perfusion MR
      imaging in the entire population (0.88 vs 0.85), in group A (0.86 vs 0.82), and
      in group B (0.93 vs 0.90). CONCLUSION: Stress first-pass perfusion MR imaging
      followed by delayed-enhancement imaging is an accurate method to depict
      significant coronary stenosis in patients suspected of having or known to have
      CAD.

PMID- 16793973
TI  - Colonic polyps: effect of attenuation of tagged fluid and viewing window on
      conspicuity and measurement--in vitro experiment with porcine colonic specimen.
AB  - PURPOSE: To investigate effect of attenuation of tagged fluid and viewing window
      on polyp conspicuity and measurement with porcine colonic specimen. MATERIALS AND
      METHODS: Eleven (3-10-mm-diameter) polyps were created in porcine colon and the
      specimen submerged in saline. Four-detector row CT was performed after gas
      distension and after filling with six barium sulfate suspensions (attenuation,
      100-1000 HU). Two readers independently measured maximal two-dimensional polyp
      diameter on each data set with the following four viewing windows and window
      levels and window widths, respectively: colon (-150 HU, 1500 HU), lung (-500 HU,
      1500 HU), bone (500 HU, 2500 HU), and abdomen (40 HU, 400 HU). In consensus,
      polyp conspicuity (compared with air data set) was assigned a grade of 1-4 for
      each viewing window (grade 1, not seen or barely visible; grade 4, optimally
      seen). For statistical analysis, conspicuity grades were collapsed to a two-point
      scale. Data were analyzed with Mann-Whitney, Kruskal-Wallis, and chi2 tests.
      RESULTS: Accuracy of polyp measurement was independent of viewing window for
      attenuation of tagged fluid of 100-300 HU but differed significantly for 500-1000
      HU (P < .001); that for colonic and bone viewing windows was superior (median
      size difference, 1.0 mm; interquartile range, 0.5-1.5). Conspicuity differed
      significantly according to viewing window at all attenuation values (P < .001).
      For 100-300 HU with abdominal viewing window, 83% (24 of 29) of observations were
      assigned grade 3 or 4 (best). For 500-1000 HU with bone viewing window, 94% (30
      of 32) of observations were assigned grade 3 or 4 (superior). Overall conspicuity
      was best with bone viewing windows at 700 HU. CONCLUSION: Polyp conspicuity and
      measurement in tagged data sets were optimized at 700 HU with bone viewing
      windows. At less than 300 HU, conspicuity improved with abdominal viewing
      windows.

PMID- 16793972
TI  - Angiogenesis inhibitors in a murine neuroblastoma model: quantitative assessment
      of intratumoral blood flow with contrast-enhanced gray-scale US.
AB  - PURPOSE: To quantify intratumoral ultrasonographic (US) contrast agent flow at
      gray-scale imaging as a measure of functional tumor vascularity in an orthotopic
      murine neuroblastoma model treated with angiogenesis inhibitors. MATERIALS AND
      METHODS: After Institutional Animal Care and Use Committee approval,
      retroperitoneal neuroblastomas were established in mice with unmodified NXS2
      cells (n = 13) or with cells engineered to overexpress an angiogenesis inhibitor-
      either tissue inhibitor of matrix metalloproteinase-3 (n = 22) or a truncated
      soluble form of the vascular endothelial growth factor receptor-2 (truncated
      soluble fetal liver kinase-1; n = 13). When tumors were approximately 600 mm3,
      contrast material-enhanced gray-scale US was performed, and the imaging was
      recorded on cine clips. Regions of interest within tumors were analyzed off-line
      to determine postcontrast change in signal intensity (SI) from baseline to
      initial peak (deltaSI), rate of SI increase from baseline to initial peak (RSI),
      and contrast material washout. The Mann-Whitney test was used to evaluate
      potential differences in these US parameters between treatment groups. The mean
      intratumoral endothelial cell (CD34) and pericyte (smooth muscle actin [SMA])
      counts at immunohistochemical analysis were also evaluated. Spearman correlation
      test was used to investigate the relation between US parameters and these
      histologic markers. RESULTS: The deltaSI and RSI were lower in tumors
      overexpressing an angiogenesis inhibitor than in control tumors (all P < .03).
      Contrast material washout did not differ between groups. For the entire cohort,
      the RSI correlated with the immunohistochemical assessment of tumor vascularity
      (SMA and CD34 counts) (P < .003). CONCLUSION: Quantification of intratumoral flow
      of a US contrast agent at gray-scale imaging shows promise for monitoring tumor
      vascular response to antiangiogenic therapy.

PMID- 16793974
TI  - Assessment of cardiovascular risk status at CT colonography.
AB  - PURPOSE: To retrospectively determine whether calcium scores of the abdominal
      aorta obtained during computed tomographic (CT) colonography relate to Framingham
      risk factors and clinical cardiac events. MATERIALS AND METHODS: The
      institutional review board approved the current HIPAA-compliant retrospective
      study and waived informed consent. Between 1995 and 1998, 480 patients underwent
      CT colonography; 467 patients were available for assessment. Calcium scores with
      a threshold attenuation value of 130 HU or greater were recorded for abdominal
      aorta (suprarenal, infrarenal, and aortic bifurcation regions and total). Patient
      histories were abstracted for established cardiac risk factors and subsequent
      cardiac events. Associations between calcium measurements and binary risk factors
      were assessed with Wilcoxon rank sum test; those with continuous risk factors,
      with Spearman rank correlation coefficient; and those with combined end points,
      with Cox proportional hazards model. RESULTS: Follow-up data were available for
      467 patients with median age of 65 years (range, 34-83 years); 59% (275 of 467)
      were men. Nine patients had cardiac events subsequent to CT colonography. Results
      of proportional hazards regression analysis revealed a significant association
      between myocardial infarction or cardiac event-related death and calcium scores
      of the aortic bifurcation that exceeded 895, the value for the 75th percentile
      for this calcium variable (P < .01). Associations with established cardiac risk
      factors for all four calcium scores were significant (P < .05). Spearman rank
      correlation coefficients for associations between total calcium score and patient
      characteristics of age, number of pack-years of smoking, and systolic blood
      pressure were 0.51, 0.43, and 0.29, respectively (P < .001 for all). CONCLUSION:
      Aortic calcification scores at CT colonography are significantly associated with
      established cardiac risk factors and cardiac-related events. This screening
      information can be obtained without additional scanning or risk to the patient.

PMID- 16793975
TI  - Statin therapy at carotid angioplasty and stent placement: effect on procedure
      related stroke, myocardial infarction, and death.
AB  - PURPOSE: To retrospectively determine if preprocedural statin treatment is
      associated with a reduction of cardiovascular events after carotid angioplasty
      and stent placement (CAS) in patients with symptomatic carotid stenosis.
      MATERIALS AND METHODS: A study resulting in a prospective database was approved
      by the institutional ethics review board; written informed consent was obtained.
      The approval and informed consent included future retrospective analysis.
      Consecutive patients (n = 180) from the prospective database underwent CAS for
      high-grade symptomatic carotid disease. The frequency of cardiovascular
      complications (composite of stroke, myocardial infarction, and death within 30
      days after CAS) between 127 patients without preprocedural statin treatment and
      that of 53 patients with preprocedural statin treatment at CAS were compared with
      chi2 and multivariate logistic regression analysis. RESULTS: The overall 30-day
      myocardial infarction rate was two of 180 (1%) patients, the minor stroke rate
      was 16 of 180 (9%) patients, the major stroke rate was one of 180 (0.5%)
      patients, and the death rate was two of 180 (1%) patients. The incidence of
      cardiovascular events (composite of stroke, myocardial infarction, and death
      within 30 days after CAS) was significantly different between patients with
      preprocedural treatment (4%) and those without preprocedural statin treatment
      (15%) (P < .05). These higher complication rates among patients without
      preprocedural statin treatment were not mediated by adjustment for age, sex,
      other baseline characteristics, degree of carotid stenosis, use of cerebral
      protection devices, or the year in which CAS was performed. CONCLUSION:
      Preprocedural statin therapy appears to reduce the incidence of stroke,
      myocardial infarction, and death within 30 days after CAS. Future prospective
      randomized trials are warranted to further assess this potential protective
      effect of statin drugs during carotid interventions.

PMID- 16793976
TI  - MR imaging features of radial tunnel syndrome: initial experience.
AB  - PURPOSE: To retrospectively assess magnetic resonance (MR) imaging features of
      radial tunnel syndrome. MATERIALS AND METHODS: Institutional review board
      approval was obtained, and informed consent was waived for the retrospective
      HIPAA-compliant study. MR images of 10 asymptomatic volunteers (six men, four
      women; mean age, 30 years) and 25 patients (11 men, 14 women; mean age, 49 years)
      clinically suspected of having radial tunnel syndrome were reviewed for
      morphologic and signal intensity alterations of the posterior interosseous nerve
      and adjacent soft-tissue structures. MR images of the asymptomatic volunteers
      were reviewed to establish the normal appearance of the radial tunnel. MR images
      of the symptomatic patients were evaluated for the following: signal intensity
      alteration and morphologic alteration of the posterior interosseous nerve; the
      presence of mass effect on the posterior interosseous nerve such as the presence
      of bursae, a thickened leading edge of the extensor carpi radialis brevis, or
      prominent radial recurrent vessels; signal intensity alteration within the
      depicted forearm musculature such as edema or atrophy; and signal intensity
      changes at the origin of the common extensor and common flexor tendons, which
      would suggest a diagnosis of epicondylitis. RESULTS: All images of volunteers
      demonstrated normal morphology and signal intensity within the posterior
      interosseous nerve and adjacent soft tissues. Two volunteers had borderline
      thickening of the leading edge of the extensor carpi radialis brevis. Thirteen
      patients (52%) had denervation edema or atrophy within muscles (supinator and
      extensors) innervated by the posterior interosseous nerve. One patient had
      isolated pronator teres edema. Seven (28%) patients had the following mass
      effects along the posterior interosseous nerve: thickened leading edge of the
      extensor carpi radialis brevis (n = 4), prominent radial recurrent vessels (n =
      1), schwannoma (n = 1), or bicipitoradial bursa (n = 1). The rest of the patients
      had either normal MR imaging findings (n = 4) or lateral epicondylitis (n = 2).
      CONCLUSION: Muscle denervation edema or atrophy along the distribution of the
      posterior interosseous nerve is the most common MR finding in radial tunnel
      syndrome.

PMID- 16793977
TI  - Occult scaphoid fractures: comparison of multidetector CT and MR imaging--initial
      experience.
AB  - PURPOSE: To compare the diagnostic performance of multidetector computed
      tomography (CT) and magnetic resonance (MR) imaging in patients clinically
      suspected of having a scaphoid fracture and who had normal initial radiographs,
      with radiographs obtained 6 weeks after trauma as the reference standard.
      MATERIALS AND METHODS: The ethics committee approved the study, and all patients
      gave written informed consent. Twenty-nine patients (17 male, 12 female; age
      range, 17-62 years; mean age, 34 years +/- 13) underwent multidetector CT and MR
      imaging within 6 days after trauma. CT data were obtained with 0.5-mm
      collimation. For image review, 0.7-mm-thick multiplanar reformations were
      performed in transverse, coronal, and sagittal planes relative to the wrist. The
      1.0-T MR examination consisted of coronal and transverse short inversion time
      inversion-recovery, coronal and transverse T1-weighted spin-echo, and coronal
      volume-rendered T2-weighted gradient-echo sequences. Two radiologists analyzed
      the CT and MR images. A binomial test was used to evaluate the significance of
      the differences between MR imaging and CT in detection of scaphoid fractures and
      cortical involvement (P < .05). RESULTS: The 6-week follow-up radiographs
      depicted a scaphoid fracture in 11 (38%) patients. Eight patients had a cortical
      fracture, while three patients had only a bandlike lucency within the trabecular
      portion of the scaphoid. MR imaging depicted all 11 fractures but only three
      [corrected] cortical fractures. Multidetector CT depicted all eight cortical
      fractures but failed to depict trabecular fractures. No false-positive fractures
      were seen on MR or CT images. Differences between MR imaging and CT were not
      significant for the detection of scaphoid fractures (P = .25) but were
      significant for cortical involvement (P = .03). CONCLUSION: Multidetector CT is
      highly accurate in depicting occult cortical scaphoid fractures but appears
      inferior to MR imaging in depicting solely trabecular injury. MR imaging is
      inferior to multidetector CT in depicting cortical involvement.

PMID- 16793978
TI  - Fetal lung volume measurements: determination with MR imaging--effect of various
      factors.
AB  - PURPOSE: To retrospectively determine the effect of gestational age (GA), imaging
      plane, section thickness, and inter- and intraobserver variability on fetal lung
      volume (FLV) measurements obtained with magnetic resonance (MR) imaging in a
      cohort of fetuses without thoracic abnormalities. MATERIALS AND METHODS:
      Institutional review board approval was obtained. Informed consent for this
      retrospective cohort study was waived, and the conduct of this study was HIPAA
      compliant. FLV was measured in 30 fetuses (GA, 17-36 weeks) referred for MR
      imaging for indications other than pulmonary abnormalities. Measurements were
      made on single-shot fast spin-echo images by tracing free-form regions of
      interest on individual consecutive sections in the transverse, sagittal, and
      coronal planes. Measurements were performed twice by two observers independently.
      Correlations between FLV and GA, imaging plane, and section thickness were
      assessed, as were intra- and interobserver variability. Time to perform FLV was
      assessed in a subset of fetuses. RESULTS: Total FLV ranged from 2 to 110 mL.
      Mixed-effects regression model showed significant quadratic trend in FLV with
      increasing GA, with comparable strength of correlation (r = 0.89-0.91) in the
      three imaging planes of measurement. Intraobserver agreement was good in all
      three planes (r = 0.65-0.83) and was highest in the transverse plane.
      Interobserver agreement was good in all three planes (r = 0.68-0.76). FLV showed
      no significant dependence on section thickness (P = .23) or imaging plane (P =
      .82). Mean time to obtain FLV measurements ranged from 48 seconds at GA of 21
      weeks to 77 seconds at GA of 29-30 weeks. CONCLUSION: GA-based FLV measurements
      obtained with MR images are independent of section thickness and imaging plane
      and can be performed with good inter- and intraobserver agreement in less than 2
      minutes.

PMID- 16793979
TI  - Limbic tract anomalies in pediatric myelomeningocele and Chiari II malformation:
      anatomic correlations with memory and learning--initial investigation.
AB  - PURPOSE: To prospectively determine anomalies of limbic tracts and to describe
      the relationship between these anomalies, seen on diffusion-tensor magnetic
      resonance (MR) and fiber tract (FT) reconstruction images, and learning and
      memory in children with myelomeningocele (MM) and Chiari II malformation.
      MATERIALS AND METHODS: The investigation was HIPAA compliant and approved by
      institutional review boards; informed consent was obtained. In seven male and six
      female patients (aged 6 months to 16 years) with MM and Chiari II malformation,
      diffusion-tensor imaging and FT reconstruction were performed. FT reconstruction
      was generated with fractional anisotropy continuous tracking algorithm and
      manually drawn regions of interest. Limbic tract abnormalities were assessed on
      FT reconstruction images by an experienced pediatric neuroradiologist blinded to
      results of cognitive testing. Nine patients met criteria for memory and learning
      testing by a trained cognitive neuroscientist blinded to MR results. Exact
      Wilcoxon rank sum test was used to compare performance with learning and memory
      tasks in two groups. RESULTS: Eleven of 13 patients had defects within fornices
      and/or cingulum; three patients had aberrant fibers of cingulum. In nine
      patients, six had deficits in general memory; four, in learning; and four, in
      both. Atresia or hypoplasia of crura and body of fornices was noted in six
      patients with memory deficits and four patients with learning deficits. Five of
      six patients with memory deficits and three of four with learning deficits had
      hypoplasia or atresia of cingulum. Exact Wilcoxon rank sum test demonstrated
      significantly poorer performance for nonverbal immediate recall tasks in patients
      with anomalies of the fornix compared with those without (P = .04, exact two
      tailed test). CONCLUSION: Diffusion-tensor and FT reconstruction images revealed
      that limbic fiber abnormalities were common in patients with MM and Chiari II
      malformation. Nonverbal immediate recall task performance appeared to be related
      to abnormalities of the fornix.

PMID- 16793980
TI  - Automatic quantitative left ventricular analysis of cine MR images by using three
      dimensional information for contour detection.
AB  - The purpose of this study was to evaluate an automatic boundary detection
      algorithm of the left ventricle on magnetic resonance (MR) short-axis images with
      the essential restriction of no manual corrections. The study comprised 13
      patients (nine men, four women) and 12 healthy volunteers (11 men, one woman),
      and institutional review board approval and informed consent were obtained. The
      outline of the left ventricle was indicated manually on horizontal and vertical
      long-axis MR images. The calculated intersection points with the short-axis MR
      images were the basis of the automatic contour detection. Automatically derived
      volumes correlated highly with manually derived (short axis-based) volumes (R2 =
      0.98); ejection fraction (EF) and mass showed a correlation of 0.95 and 0.93,
      respectively. Automatic contour detection reduced interobserver variability to
      0.1 mL for endocardial end-diastolic and end-systolic volumes, 1.1 mL for
      epicardial end-diastolic and end-systolic volumes, 0.02% for EF, and 1.1 g for
      mass. Thus, the algorithm enabled highly reproducible left ventricular parameters
      to be obtained.

PMID- 16793981
TI  - Contrast-enhanced MR angiography of the peripheral vasculature with a
      continuously moving table and modified elliptical centric acquisition.
AB  - This study was approved by the institutional review board and was HIPAA
      compliant. All subjects provided written informed consent, and subject
      confidentiality was protected. The purpose of this study was to prospectively
      evaluate the feasibility of integrating a modified elliptical centric (EC)
      acquisition with a continuously moving table technique to acquire high-spatial
      resolution contrast material-enhanced magnetic resonance (MR) angiograms of the
      peripheral vasculature. Incorporation of two-dimensional homodyne reconstruction
      modified the EC view order, allowing improved spatial resolution per unit time
      while retaining the advantage of venous suppression intrinsic to the EC
      technique. Spatial resolution was dynamically improved when the table reached the
      distal-most station. The modified view order provided improved spatial resolution
      in phantom examinations compared with that in standard examinations. Peripheral
      MR angiograms were generated in a group of 13 volunteers (eight women; five men;
      age range, 51-72 years; mean age, 58.5 years +/- 7.9 [standard deviation]) at 1.5
      T. Four arterial regions were evaluated on a five-point scale (scores ranged from
      0 to 4; a score of 4 was considered excellent); venous suppression was also
      evaluated. The mean arterial scores exceeded 3.0 for all regions. There was no
      venous signal or only superficial venous signal in 10 of the 13 cases.

PMID- 16793982
TI  - Thin-section CT in patients with cystic fibrosis: correlation with peak exercise
      capacity and body mass index.
AB  - PURPOSE: To evaluate whether thin-section chest computed tomographic (CT)
      findings correlate with exercise capacity, body mass index (BMI), dyspnea, and
      leg discomfort in patients with cystic fibrosis (CF). MATERIALS AND METHODS:
      Institutional ethics committee approval was obtained, and patients provided
      written informed consent. Twenty-two patients (13 male and nine female patients;
      mean age, 22 years +/- 5.9; age range, 17-41 years) with stable CF underwent thin
      section CT and exercise testing on a cycle ergometer. Three radiologists blinded
      to the clinical severity of disease and the spirometric findings of all patients
      independently and randomly scored all scans with a modified Bhalla scoring
      system. The primary measurement of the outcome of exercise testing was percentage
      of predicted peak O2 uptake. Univariate (Spearman rank correlation) and
      multivariate analyses were used to compare thin-section CT, clinical (age, sex,
      spirometric data, and BMI), and exercise measurements. RESULTS: The correlation
      between total thin-section CT score and percentage of predicted peak O2 uptake
      was stronger than the correlation between the percentage of predicted peak O2
      uptake and any clinical measurement (R = -0.60, P < .01). The thin-section CT
      structural abnormalities that had the strongest correlation with percentage of
      predicted peak O2 uptake were severity of bronchiectasis and presence of
      sacculations or abscesses (R = -0.70 and -0.71, respectively; P < .01).
      Multivariate analysis showed total thin-section CT score to be the only
      significant predictor of exercise capacity, accounting for 42% of the variance in
      percentage of predicted peak O2 uptake. CONCLUSION: In patients with CF, the
      correlation between thin-section CT score and exercise limitation is stronger
      than that between spirometry results or BMI and exercise limitation.

PMID- 16793983
TI  - Uterine leiomyomas: MR imaging-based thermometry and thermal dosimetry during
      focused ultrasound thermal ablation.
AB  - PURPOSE: To retrospectively evaluate magnetic resonance (MR) imaging-based
      thermometry and thermal dosimetry during focused ultrasound treatments of uterine
      leiomyomas (ie, fibroids). MATERIALS AND METHODS: All patients gave written
      informed consent for the focused ultrasound treatments and the current HIPAA
      compliant retrospective study, both of which were institutional review board
      approved. Thermometry performed during the treatments of 64 fibroids in 50 women
      (mean age, 46.6 years +/- 4.5 [standard deviation]) was used to create thermal
      dose maps. The areas that reached dose values of 240 and 18 equivalent minutes at
      43 degrees C were compared with the nonperfused regions measured on contrast
      material-enhanced MR images by using the Bland-Altman method. Volume changes in
      treated fibroids after 6 months were compared with volume changes in nontreated
      fibroids and with MR-based thermal dose estimates. RESULTS: While the thermal
      dose estimates were shown to have a clear relationship with resulting nonperfused
      regions, the nonperfused areas were, on average, larger than the dose estimates
      (means of 1.9 +/- 0.7 and 1.2 +/- 0.4 times as large for areas that reached 240-
      and 18-minute threshold dose values, respectively). Good correlation was observed
      for smaller treatment volumes at the lower dose threshold (mean ratio, 1.0 +/-
      0.3), but for larger treatment volumes, the nonperfused region extended to
      locations within the fibroid that clearly were not heated. Variations in peak
      temperature increase were as large as a factor of two, both between patients and
      within individual treatments. On average, the fibroid volume reduction at 6
      months increased as the ablated volume estimated by using the thermal dose
      increased. CONCLUSION: Study results showed good correlation between thermal dose
      estimates and resulting nonperfused areas for smaller ablated volumes. For larger
      treatment volumes, nonperfused areas could extend within the fibroid to unheated
      areas.

PMID- 16793984
TI  - Outcomes of tracheobronchial stent placement for benign disease.
AB  - PURPOSE: To retrospectively determine long-term outcomes in patients who have
      undergone tracheobronchial stent placement for benign diseases. MATERIALS AND
      METHODS: Institutional Review Board approval was obtained for this retrospective
      HIPAA-compliant study, with waiver of informed consent. Forty patients (22
      female, 18 male; mean age, 52.0 years) who were treated with metallic airway
      stents for benign stenosis were identified from an interventional radiology
      database. Causes of airway stenosis included transplant stricture (n = 13),
      tracheal tube injury (n = 10), inflammation (n = 6), tracheobronchomalacia (n =
      4), infection (n = 3), and extrinsic compression (n = 4). Follow-up, which ranged
      from 6 to 2473 days, was performed by means of chart review for deceased patients
      and by means of clinical visit or telephone interview for surviving patients.
      Survival, primary patency, and assisted patency were estimated by using the
      Kaplan-Meier product limits method. RESULTS: Initial technical success was
      achieved in all cases. Symptomatic improvement was present in 39 of 40 cases. At
      review, 15 patients were alive and had clinical improvement, 18 had died of
      comorbid causes, one had died of uncertain causes, three had undergone subsequent
      airway surgery, two had undergone airway stent retrieval, and one was lost to
      follow-up. Survival at 1, 2, 3, 4, 5, and 6 years was 79%, 76%, 51%, 47%, 38%,
      and 23%, respectively. Loss of primary patency was most rapid during the 1st
      year. With repeat intervention, assisted patency was 90% at 6.8 years.
      CONCLUSION: Attrition of tracheobronchial stent patency is most rapid during the
      1st year, and a high rate of long-term patency can be achieved with secondary
      interventions. Metallic airway stents are well-tolerated and useful adjuncts for
      management of select benign tracheobronchial stenoses.

PMID- 16793987
TI  - Case 96: Hepatic epithelioid hemangioendothelioma.

PMID- 16793988
TI  - The cord sign.

PMID- 16793989
TI  - Renal safety of gadolinium-based contrast agent for ionizing radiation imaging.

PMID- 16793990
TI  - First challenge of MR versus CT peripheral angiography: how to identify a winner?

PMID- 16793991
TI  - A comparative approach to somatic cell nuclear transfer in the rhesus monkey.
AB  - BACKGROUND: Despite the potential utility of primate somatic cell nuclear
      transfer (SCNT) to biomedical research and to the production of autologous
      embryonic stem (ES) cells for cell- or tissue-based therapy, a reliable method
      for SCNT is not yet available. Employing the rhesus monkey as a clinically
      relevant animal model, we have compared a conventional electrofusion method for
      SCNT with a one-step micromanipulation (OSM) method. METHODS: A prospective,
      randomized trial was conducted using only oocytes that were mature [metaphase II
      (MII)] at collection and a fibroblast-like cell line as nuclear donor cells
      (fetal fibroblasts). The embryos produced were characterized for in vitro
      developmental potential, cell number, karyotype and expression of nuclear mitotic
      apparatus (NuMA) and OCT-4. RESULTS: An in vitro blastocyst development rate of
      24.4% was achieved with the OSM method, significantly higher than the 12.2%
      obtained following electrofusion. SCNT-produced embryos expressed normal
      karyotypes, cell numbers and NuMA and OCT-4 proteins in most cases. SCNT with
      male nuclear donor cells resulted in the production of male, SCNT blastocysts,
      eliminating the possibility of a parthenogenetic origin. Of the four fibroblast
      cell lines tested as nuclear donor cells, two supported the routine production of
      blastocysts following SCNT. CONCLUSIONS: The application of a modified SCNT
      technique (OSM) followed by embryo culture in hamster embryo culture medium-10
      (HECM-10) allows, for the first time, the routine production of SCNT blastocysts,
      most of which appear normal by immunochemical, cytochemical and in vitro
      developmental criteria. These embryos will provide a resource for isolating ES
      cells and for studies of nuclear reprogramming by monkey cytoplasts.

PMID- 16793992
TI  - Sperm DNA fragmentation: paternal effect on early post-implantation embryo
      development in ART.
AB  - BACKGROUND: The relationship between early embryo post-implantation development
      in couples undergoing assisted reproductive techniques (ARTs) and sperm chromatin
      alterations has not been satisfactorily explained. The aim of this study was to
      assess the relationship between sperm DNA fragmentation in IVF/ICSI patients,
      sperm parameters (concentration, motility and morphology) and ART outcome,
      especially with regard to clinical pregnancy and pregnancy loss (spontaneous
      miscarriage or biochemical pregnancy). METHODS: DNA fragmentation was evaluated
      by TUNEL assay, performed on sperm suspensions after density gradient separation,
      in 132 men undergoing an ART cycle (82 IVF and 50 ICSI) and correlated with sperm
      parameters and ART outcome. RESULTS: A highly significant negative correlation
      was found between DNA fragmentation and sperm parameters. There was a close
      relationship between DNA fragmentation and post-implantation development in ICSI
      patients: the clinical pregnancy and pregnancy loss rates significantly differed
      between patients with high and low sperm DNA fragmentation (P = 0.007 and P =
      0.009, respectively). CONCLUSIONS: Sperm DNA fragmentation seems to affect embryo
      post-implantation development in ICSI procedures: high sperm DNA fragmentation
      can compromise 'embryo viability', resulting in pregnancy loss.

PMID- 16793993
TI  - Quantitative effects of male age on sperm motion.
AB  - BACKGROUND: Semen quality is associated with fertility status, but there is
      little quantitative information on risk factors that affect semen quality,
      especially in non-clinical populations. Advancing male age has been associated
      with a decline in semen quality, with the largest effect being on sperm motility.
      However, there is little quantitative data on the specific components of sperm
      motion that are affected by male age. METHODS: We performed linear regression
      analyses of 14 aspects of semen quality measured by computer-assisted semen
      analysis (CASA) in a non-clinical cohort of 90 non-smoking men, aged 22-80 years,
      who had no history of infertility or reproductive problems. RESULTS: We found age
      associated declines in CASA-determined motility (% motile, 0.8% per year; %
      progressively motile, 0.9% per year; % rapidly motile, 0.4% per year, P <or=
      0.001) and three quantitative aspects of sperm motion [linearity (LIN), 0.2% per
      year; straight line velocity (VSL), 0.2% per year, and average path velocity
      (VAP), 0.3% per year, P < 0.05], with no evidence for age thresholds and no
      significant association with abstinence duration. Age was not significantly
      associated with amplitude of lateral head (ALH) displacement, beat cross
      frequency (BCF) and nuclear elongation or size. CONCLUSIONS: Quantitative
      analysis of sperm motion indicates that as men age, they produce fewer motile
      sperm, which are able to travel less along a linear path, thus covering less
      forward distance per unit time. These findings may have fertility implications
      for men who choose to delay fatherhood.

PMID- 16793994
TI  - Is twin pregnancy necessarily an adverse outcome of assisted reproductive
      technologies?
AB  - It has recently been suggested that the measure of success of assisted
      reproductive technologies (ART) should be the birth of a singleton baby, whereas
      a twin pregnancy should be considered as a complication. Although the maternal
      and neonatal complications in twin pregnancies are significantly higher than
      those in singleton pregnancies, the classification of a twin pregnancy as a
      complication of ART is in our opinion debatable. Most twin pregnancies result in
      the birth of two healthy babies, with little or no complication for the mother,
      and only few twin pregnancies results in serious morbidity of the mother and of
      one or both of the children. The crux of our arguments is that one should
      consider those cases as poor outcomes and not a twin pregnancy per se.

PMID- 16793995
TI  - Evidence of improving quality of reporting of randomized controlled trials in
      subfertility.
AB  - BACKGROUND: The quality of randomized controlled trials (RCTs) in subfertility
      and their suitability for inclusion in meta-analyses have been assessed in the
      past and found to be insufficient. Our aim was to assess whether this quality has
      improved over time, particularly since the publication of the Consolidated
      Standards of Reporting Trials (CONSORT) statement, and to assess what proportion
      of trials could be included in the meta-analyses of pregnancy outcomes such as
      those included in Cochrane Reviews. METHODS: A selection of subfertility trials
      published in 1990, 1996 and 2002 was collected from the Cochrane Menstrual
      Disorder and Subfertility Group (MDSG) database. Only trials published in English
      as full journal articles, claiming to be randomized and reporting on pregnancy
      outcomes, were included. RESULTS: One hundred and sixty-four trials met our
      inclusion criteria. Twenty-four (15%) were found not to be randomized, despite
      claims, and only 10 trials (6%) provided adequate details on the methods of
      randomization and allocation concealment. Of these, only three had sufficient
      details extractable to allow for an intention-to-treat analysis of the outcome
      'live birth'. CONCLUSIONS: Although an improvement in some subfertility-specific
      issues was observed, the quality of reporting of RCTs still needs to improve to
      make them suitable for inclusion in meta-analyses such as those in the Cochrane
      Library.

PMID- 16793996
TI  - Of rats and men (and women).

PMID- 16793997
TI  - Smoking history effect on peripheral lung inflammation and gene transcription in
      chronic obstructive pulmonary disease.

PMID- 16793998
TI  - A CAP on antibiotic duration.

PMID- 16793999
TI  - Amphotericin B is still the drug of choice for invasive aspergillosis.

PMID- 16794000
TI  - Video-assisted thoracic surgery versus medical thoracoscopic talc poudrage in
      spontaneous pneumothorax.

PMID- 16794001
TI  - Prolactin-releasing Peptide mediates cholecystokinin-induced satiety in mice.
AB  - We have shown previously that prolactin-releasing peptide (PrRP) plays a role in
      the regulation of feeding and energy expenditure in rats. We hypothesize that
      PrRP may have a physiological action through its putative receptor, GPR10, to
      mediate the central anorexigenic effects of peripheral satiety factors. Here we
      examine the effects of PrRP and cholecystokinin (CCK) on feeding in mice,
      including PrRP receptor gene knockout animals (GPR10(-/-)).
      Intracerebroventricular administration of PrRP (1-4 nmol) inhibited feeding in
      C57B6/J mice under both fast-induced and nocturnal feeding conditions. In
      contrast to the observations made in wild-type mice, neither PrRP nor CCK reduced
      food intake in GRP10(-/-) mice. The reduction in feeding and the release of
      corticosterone induced by systemic injection of the stressor lipopolysaccharide
      was similar in both GPR10(+/+) and GPR10(-/-) mice. These findings suggest that
      PrRP, acting through GPR10, is involved in regulating food intake and may be a
      key intermediary in the central satiating actions of CCK.

PMID- 16794002
TI  - Proteomic identification of AP2 gamma as a rat placental lactogen II trophoblast
      cell-specific enhancer binding protein.
AB  - The factors that regulate the developmental expression of the rodent prolactin
      gene family in placenta remain poorly defined. We previously identified an
      enhancer element in the 5' flanking region of one family member, rat placental
      lactogen II (rPLII), which could target reporter gene expression to the placenta
      in transgenic mice; this enhancer functioned in the Rcho rat trophoblast cell
      line but not in the rat pituitary GC cell line. In further experiments to
      identify the factors that bind this element, we have selectively enriched for DNA
      binding proteins in nuclear extract from Rcho cells using magnetic beads coupled
      to a 43-bp enhancer oligonucleotide. Tryptic peptides of bound proteins were
      analyzed by HPLC coupled off-line to matrix-assisted laser desorption ionization
      time of flight mass spectrometry. Several peptides of AP2 gamma, a key
      trophoblast cell-specific transcription factor, were identified. Gel mobility
      shift assays using AP2 gamma-specific antiserum and mutant enhancer
      oligonucleotides demonstrated binding specifically to the FP2 DNase I-protected
      region of the element, identifying an atypical binding site for this factor. In
      cotransfection assays in rat pituitary GC cells, AP2 gamma transactivated the
      enhancer via this region. Chromatin immunoprecipitation assays confirmed AP2
      gamma occupancy of the enhancer region in situ in the nuclei of Rcho giant cells.
      These data support a role for AP2 gamma in the placental giant cell-specific
      expression of the rPLII gene and provide the first direct evidence for the
      involvement of a placental-specific transcription factor in the regulation of a
      member of this gene family.

PMID- 16794003
TI  - Sphingosine 1-phosphate affects cytokine-induced apoptosis in rat pancreatic
      islet beta-cells.
AB  - Cytokines mediate pancreatic islet beta-cell apoptosis and necrosis, leading to
      loss of insulin secretory capacity and type 1 diabetes mellitus. The cytokines,
      IL-1beta and interferon-gamma, induced terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining of rat
      islet cells within 48 h by about 25-30%, indicative of apoptosis and/or necrosis.
      Sphingosine 1-phosphate (S1P) at nanomolar concentrations significantly reduced
      islet cell cytokine-induced TUNEL staining. Similar effects were observed in INS
      1 cells. The dihydro analog of S1P also reduced the percentage of TUNEL stained
      islet and INS-1 cells, whereas the S1P receptor antagonist BML-241 blocked the
      protective effects. Pertussis toxin did not affect the S1P protective response.
      In the presence of a phospholipase C antagonist, U73122, there was significant
      inhibition of the S1P protective effects against apoptosis/necrosis. S1P
      stimulated INS-1 cell protein kinase C activity. Carbamylcholine chloride acting
      through muscarinic receptors also inhibited cytokine-induced TUNEL staining in
      pancreatic islet cells. S1P and/or dihydro-S1P also antagonized cytokine-induced
      increases in cytochrome c release from mitochondria and caspase-3 activity in INS
      1 cells, which are indicative of cell apoptosis vs. necrosis. S1P failed to
      affect nitric oxide synthase activity after 48 h. Thus, the evidence suggests
      that S1P acting on S1P receptors coupled to G(q) mediates protective effects on
      islet beta-cells against cytokine-induced apoptosis.

PMID- 16794004
TI  - Biological properties of a novel follicle-stimulating hormone/human chorionic
      gonadotropin chimeric gonadotropin.
AB  - A chimeric recombinant human gonadotropin, termed C3, demonstrates both
      follitropic and lutropic bioactivities. The alpha-subunit construct for C3 is
      comprised of the recombinant wild-type human glycoprotein hormone alpha-subunit.
      The beta-subunit DNA construct for C3 encodes residues 1-145 from human chorionic
      gonadotropin (hCG)-beta with the exceptions that FSH beta amino acid 88 (D) is
      substituted for hCG beta amino acid 94 (R) and FSH beta amino acids 95-108
      (TVRGLGPSYCSFGE) are substituted for hCG beta amino acids 101-114
      (GGPKDHPLTCDDPR). C3 is a potent FSH and LH agonist able to bind and to signal
      through FSH and LH receptors in vitro. In in vivo bioassays optimized to quantify
      each type of activity, C3 was found to have lutropin and follitropin potencies at
      levels similar to those of recombinant human LH and recombinant human FSH,
      respectively. In immature rats, C3 was sufficient to support the maturation of
      normal ovarian follicles. Moreover, a significant portion of follicles matured by
      C3 ruptured in response to an ovulatory hCG stimulus and gave rise to
      morphologically normal oocytes. Furthermore, a low dose of C3 promoted weight
      gain in the rodent uterus, suggesting it also supported preparation for
      implantation without histological evidence of excessive luteinization of the
      ovary. In summary, the biological properties of C3 indicate that its chimeric
      nature has resulted in a fully functional, dual-acting human gonadotropin.

PMID- 16794005
TI  - Indian hedgehog, but not histidine decarboxylase or amphiregulin, is a
      progesterone-regulated uterine gene in hamsters.
AB  - Implantation occurs only in the progesterone (P4)-primed uterus in the majority
      of species, but little effort has been given to identify P4-mediated molecules in
      these species. Using hamsters as a model for P4-dependent implantation and three
      well-known uterine receptivity-associated P4-regulated genes, Indian hedgehog
      (Ihh), histidine decarboxylase (Hdc), and amphiregulin (Areg), in mice that
      require ovarian estrogen for uterine receptivity and implantation, our strategy
      aimed to determine whether P4 regulates uterine expression of these genes in
      hamsters and whether the event- and cell-specific uterine expression patterns of
      these genes during the periimplantation period in hamsters follow similarly with
      their patterns in mice. We report here that P4-mediated Ihh signaling is
      important for uterine receptivity and implantation in hamsters because uterine
      epithelial Ihh expression was regulated by P4 and its expression patterns during
      the periimplantation period of hamsters closely follow its pattern in mice. In
      contrast, we noted no hormonal regulation of Hdc and Areg in the hamster uterus.
      However, this did not diminish their importance in hamsters because their
      expression patterns and functions are event and cell specific during the
      periimplantation period: whereas Hdc was expressed exclusively in d 4 uterine
      glands and regulated by the blastocyst, Areg was expressed on the decidual area
      adjacent to the embryo from d 5 onward and involved in stromal cell
      proliferation. We conclude that similarities and dissimilarities exist in uterine
      expression pattern of implantation-related genes, including hormonal regulation
      and their event-specific importance.

PMID- 16794006
TI  - Fasting induces hyperlipidemia in mice overexpressing proprotein convertase
      subtilisin kexin type 9: lack of modulation of very-low-density lipoprotein
      hepatic output by the low-density lipoprotein receptor.
AB  - Several proprotein convertase subtilisin kexin type 9 (PCSK9) mutations lead to
      familial hypercholesterolemia by virtue of its role as a negative modulator of
      the low-density lipoprotein receptor (LDLr). Here, we uncover that upon dietary
      challenge, the down-regulation of the LDLr is also a key mechanism by which PCSK9
      modulates the hepatic production of apolipoprotein-B-containing lipoproteins.
      Thus, adenoviral-mediated overexpression of PCSK9 in 24-h fasted mice results in
      massive hyperlipidemia, due to a striking increase in very-low-density
      lipoprotein (VLDL) triglycerides and apolipoprotein B100 hepatic output. Similar
      studies in LDLr (-/-) mice demonstrate that PCSK9-mediated alteration of VLDL
      output in the fasted state requires the LDLr. This increased production of VLDL
      was associated with a concomitant reduction of intrahepatic lipid stores as well
      as a lack of down-regulation of peroxisome proliferator-activated receptor-alpha
      activity and target genes expression. Finally, we show that PCSK9 hepatic
      expression is inhibited by the hypotriglyceridemic peroxisome proliferator
      activated receptor-alpha agonist fenofibrate. In summary, the negative modulation
      of LDLr expression by PCSK9, which decreases plasma LDL clearance, also promotes
      an overproduction of nascent VLDL in vivo upon fasting.

PMID- 16794007
TI  - Cloning and characterization of an ovine intracellular seven transmembrane
      receptor for progesterone that mediates calcium mobilization.
AB  - Classically, progesterone has been thought to act only through the well-known
      genomic pathway involving hormone binding to nuclear receptors (nPR) and
      subsequent modulation of gene expression. However, there is increasing evidence
      for rapid, nongenomic effects of progesterone in a variety of tissues in mammals,
      and it seems likely that a membrane PR (mPR) is causing these events. The
      objective of this study was to isolate and characterize an ovine mPR distinct
      from the nPR. A cDNA clone was isolated from ovine genomic DNA by PCR. The ovine
      mPR is a 350-amino acid protein that, based on computer hydrophobicity analysis,
      possesses seven transmembrane domains and is distinct from the nPR. Message for
      the ovine mPR was detected in hypothalamus, pituitary, uterus, ovary, and corpus
      luteum by RT-PCR. In CHO cells that overexpressed a mPR-green fluorescent protein
      fusion protein, the ovine mPR was localized to the endoplasmic reticulum and not
      the plasma membrane. Specific binding of 3H-progesterone to membrane fractions
      was demonstrated in CHO cells that expressed the ovine mPR but not in
      nontransfected cells. Furthermore, progesterone and 17 alpha-hydroxy-progesterone
      stimulated intracellular Ca2+ mobilization in CHO cells that expressed ovine mPR
      in Ca2+-free medium (P < 0.05) but not in CHO cells transfected with empty
      vector. This rise in intracellular Ca2+ is believed to be from the endoplasmic
      reticulum as intracellular Ca2+ mobilization is absent when mPR transfected cells
      are first treated with thapsigargin to deplete Ca2+ stores from the endoplasmic
      reticulum. Isolation, identification, tissue distribution, cellular localization,
      steroid binding, and a functional response for a unique intracellular mPR in the
      sheep are presented.

PMID- 16794008
TI  - Blood-brain leptin transport and appetite and reproductive neuroendocrine
      responses to intracerebroventricular leptin injection in sheep: influence of
      photoperiod.
AB  - Impaired anorectic actions of leptin may be due to intrahypothalamic
      insensitivity and/or reduced blood-brain transport. The influence of photoperiod
      on leptin responses and leptin transport from blood into cerebrospinal fluid
      (CSF) was examined in sheep. Sheep kept on ad libitum food for 15 wk in long days
      (LD) had higher voluntary food intake and lower GnRH/LH output than in short days
      (SD). Food intake was decreased approximately 30% after intracerebroventricular
      (icv) (and not iv) leptin injection, but only in SD. GnRH/LH secretion was
      decreased after icv (but not iv) leptin in both photoperiods. Leptin
      concentrations in CSF were higher in LD than SD but correlated with plasma leptin
      only in LD. Amounts of leptin entering CSF after iv leptin injection were greater
      in LD than SD. In a separate experiment, plasma (but not CSF) leptin was higher
      in fat than thin sheep in natural summer LD and after 5 wk in SD. CSF leptin
      correlated with plasma leptin in LD but not SD. CSF leptin after iv leptin
      injection was higher in thin than fat sheep but only in LD. Endogenous CSF to
      plasma concentration ratios correlated negatively with plasma concentrations,
      indicating decreased blood-brain transport with increased leptinemia. Therefore,
      icv (and not iv) leptin inhibited appetite only in SD and decreased GnRH/LH
      output in both photoperiods, and the proportion of circulating leptin entering
      CSF was higher in LD and thinner animals. Photoperiod apparently modulates
      intrahypothalamic leptin sensitivity of appetite, but not reproductive,
      regulatory pathways, whereas photoperiod and leptinemia influence leptin blood
      brain transport.

PMID- 16794009
TI  - Treatment of autoimmune hyperthyroidism in a murine model of Graves' disease with
      tumor necrosis factor-family ligand inhibitors suggests a key role for B cell
      activating factor in disease pathology.
AB  - Hyperthyroid Graves' disease is a common autoimmune disorder mediated by
      agonistic antibodies to the TSH receptor, termed thyroid stimulating antibodies
      (TSAbs). Recently members of the TNF superfamily, B cell activating factor (BAFF)
      and a proliferation-inducing ligand (APRIL), have been identified along with
      their receptors, B cell maturation antigen and transmembrane activator and
      calcium-modulator and cyclophilin ligand interactor, and the BAFF-specific
      receptor. BAFF is a fundamental B cell survival/maturation factor, and both BAFF
      and APRIL have been implicated in antibody production. We investigated the effect
      of interfering with BAFF- and APRIL-mediated signals in an induced model of
      Graves' disease by blockade of these factors using soluble decoy receptors. In a
      therapeutic setting in mice with established hyperthyroidism, we show that
      blockade of BAFF or BAFF+APRIL with BAFF-specific receptor-Fc and B cell
      maturation antigen-Fc, respectively, leads to significant reductions in the
      induced hyperthyroidism. This was supported by a parallel pattern of declining
      TSAbs in the responding animals. Histopathological analysis of splenic sections
      from treated animals revealed marked reductions in the B cell follicle regions,
      but staining with anti-CD138 revealed the persistence of plasma cells. Thus, the
      reductions in TSAbs in the treated animals were not related to overall plasma
      cell numbers in the secondary lymphoid organs. Our results are the first to
      demonstrate attenuation of established hyperthyroidism by therapeutic
      intervention aimed at autoreactive B cells and indicate that both BAFF and APRIL
      appear to play important roles in the development and survival of the
      autoantibody producing cells in this model.

PMID- 16794010
TI  - Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes
      survival of LNCaP cells via interaction with proapoptotic Bak.
AB  - Androgen-sensitive prostate cancer cells turn androgen resistant through complex
      mechanisms that involve dysregulation of apoptosis. We investigated the role of
      antiapoptotic Bcl-xL in the progression of prostate cancer as well as the
      interactions of Bcl-xL with proapoptotic Bax and Bak in androgen-dependent and 
      independent prostate cancer cells. Immunohistochemical analysis was used to study
      the expression of Bcl-xL in a series of 139 prostate carcinomas and its
      association with Gleason grade and time to hormone resistance. Expression of Bcl
      xL was more abundant in prostate carcinomas of higher Gleason grades and
      significantly associated with the onset of hormone-refractory disease. In vivo
      interactions of Bcl-xL with Bax or Bak in untreated and camptothecin-treated
      LNCaP and PC3 cells were investigated by means of coimmunoprecipitation. In the
      absence of any stimuli, Bcl-xL interacts with Bax and Bak in androgen-independent
      PC3 cells but only with Bak in androgen-dependent LNCaP cells. Interactions of
      Bcl-xL with Bax and Bak were also evidenced in lysates from high-grade prostate
      cancer tissues. In LNCaP cells treated with camptothecin, an inhibitor of
      topoisomerase I, the interaction between Bcl-xL and Bak was absent after 36 h,
      Bcl-xL decreased gradually and Bak increased coincidentally with the progress of
      apoptosis. These results support a model in which Bcl-xL would exert an
      inhibitory effect over Bak via heterodimerization. We propose that these
      interactions may provide mechanisms for suppressing the activity of proapoptotic
      Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to
      androgen resistance and progression of prostate cancer.

PMID- 16794011
TI  - Chronic intermittent psychosocial stress (social defeat/overcrowding) in mice
      increases the severity of an acute DSS-induced colitis and impairs regeneration.
AB  - Ulcerative colitis is a multifactorial disease, with immunological, genetic, and
      environmental factors playing an important role in its pathogenesis. Here we
      investigated the consequences of exposure to chronic psychosocial stress on the
      severity of a dextran sulfate sodium (DSS)-induced colitis in male C57BL/6 mice.
      Chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and
      overcrowding (OC, 24 h) during 19 consecutive days. SD/OC mice showed a
      diminished body weight gain, thymus-atrophy, and adrenal hypertrophy, but similar
      light-phase plasma corticosterone concentrations, compared with unstressed mice.
      In contrast, the rise in dark-phase corticosterone concentration was
      significantly attenuated in SD/OC mice, whereas plasma ACTH concentrations and
      hypothalamic CRH mRNA expression did not differ between stressed and nonstressed
      groups. Additionally, adrenal cells from SD/OC mice showed a decreased in vitro
      response to ACTH stimulation. Subsequent treatment with 1% DSS for 7 d resulted
      in a more severe intestinal inflammation in SD/OC mice, as reflected by an
      increase in body weight loss, histological damage scores, and secretion of IL-6,
      TNFalpha, and interferon-gamma from mesenteric lymph node cells and by decreased
      colon length. The impaired health status of stressed mice was also reflected by a
      significantly lower survival rate after termination of the DSS treatment. In
      conclusion, the present findings demonstrate that chronic intermittent exposure
      to a psychosocial stressor before the induction of acute DSS-colitis results in
      adrenal insufficiency, increases in the severity of the acute inflammation, and
      impairs the healing phase.

PMID- 16794012
TI  - Testosterone is required for delayed cardioprotection and enhanced heat shock
      protein 70 expression induced by preconditioning.
AB  - Ischemic preconditioning fails to confer immediate cardioprotection in the
      absence of testosterone, indicating that the hormone is required for the process.
      Here we set out to determine whether testosterone is also necessary for delayed
      cardioprotection and, if so, how it acts. Male Sprague Dawley rats (7-8 wk)
      underwent sham operation or gonadectomy without (G) or with testosterone
      replacement (GT) for 8 wk. Isolated ventricular myocytes were preconditioned
      either by metabolic inhibition or with U50,488H, a kappa-opioid receptor agonist.
      In intact rats, U50,488H was administered systemically and 24 h later the hearts
      were removed. Ventricular myocytes were then subjected to metabolic inhibition
      and anoxia and isolated hearts to regional ischemia, followed by reperfusion to
      induce injury. Both types of preconditioning significantly increased the
      viability and decreased the lactate dehydrogenase release in ventricular myocytes
      from sham rats. They also activated heat shock transcription factor-1 and
      increased heat shock protein 70 expression. In contrast, all these effects were
      absent in myocytes from G rats and were restored by testosterone replacement.
      Parallel results were found in isolated hearts. In addition, preconditioning
      improved contractile functions impaired by ischemic insults in sham and rats
      gonadectomized with testosterone replacement but not G rats. The effects of
      testosterone replacement in ventricular myocytes were abolished by androgen
      receptor blockade. In conclusion, preconditioning requires testosterone to
      increase heat shock protein 70 synthesis, which mediates delayed cardioprotection
      in the male. These effects of testosterone are mediated by the androgen receptor.

PMID- 16794013
TI  - Microarray analysis of uterine epithelial gene expression during the implantation
      window in the mouse.
AB  - In mice, the uterus becomes transiently receptive to the hatched blastocyst on
      the day of implantation to allow its attachment to the luminal epithelium and
      subsequent invasion into the uterus. This uterine preparation for implantation is
      regulated by estradiol-17beta and progesterone, acting through their
      transcription factor receptors. Using ovariectomized mice treated with
      physiological regimens of these hormones, combined with methods to isolate RNA
      specifically from the uterine epithelium followed by transcriptome analysis on
      cDNA microarrays, 222 genes whose transcript abundance was specifically increased
      by estradiol-17beta and progesterone treatment were identified. Gene ontology
      analysis revealed an emphasis on genes involved with immune responses,
      extracellular matrix metabolism, and cell-to-cell communication. In situ
      hybridization to uterine sections isolated through the first 6 d of pregnancy
      identified novel sets of genes such as Bach, Myd88, Cd14, Isg20, and Lrp2 whose
      expression was restricted to the uterine epithelium during the implantation
      window. Particularly notable was the expression of the mRNA for members of the
      signaling pathway from the Toll-like receptors to its downstream targets such as
      Irg-1. The identification of these genes showing a cell type hormonally regulated
      pattern of expression in the uterus suggests novel functions for them during
      implantation.

PMID- 16794014
TI  - Chronic ethanol feeding suppresses beta-adrenergic receptor-stimulated lipolysis
      in adipocytes isolated from epididymal fat.
AB  - Chronic ethanol consumption disrupts G protein-dependent signaling pathways in
      rat adipocytes. Because lipolysis in adipocytes is regulated by G protein
      mediated cAMP signal transduction, we hypothesized that cAMP-regulated lipolysis
      may be vulnerable to long-term ethanol exposure. Male Wistar rats were fed a
      liquid diet containing ethanol as 35% of total calories or pair-fed a control
      diet that isocalorically substituted maltose dextrins for ethanol for 4 wk.
      Lipolysis was measured by glycerol release over 1 h with or without agonists in
      adipocytes isolated from epididymal fat. Chronic ethanol feeding decreased beta
      adrenergic receptor-stimulated lipolysis, but had no effect on basal lipolysis.
      In response to beta-adrenergic activation, the early peak of cAMP accumulation
      was suppressed after ethanol feeding, although the basal cAMP concentration in
      adipocytes did not differ between pair- and ethanol-fed rats. The suppression in
      cAMP accumulation caused by ethanol feeding was associated with increased
      activity of phosphodiesterase 4. Chronic ethanol feeding also decreased beta
      adrenergic receptor-stimulated protein kinase A activation and phosphorylation of
      its downstream proteins, perilipin A and hormone-sensitive lipase, the primary
      lipase-mediating lipolysis. In conclusion, these data suggest that chronic
      ethanol feeding increased phosphodiesterase 4 activity in adipocytes, resulting
      in decreased accumulation of cAMP in response to beta-adrenergic activation and a
      suppression of beta-adrenergic stimulation of lipolysis.

PMID- 16794015
TI  - Mouse sterol response element binding protein-1c gene expression is negatively
      regulated by thyroid hormone.
AB  - Sterol regulatory element-binding protein (SREBP)-1c is a key regulator of fatty
      acid metabolism and plays a pivotal role in the transcriptional regulation of
      different lipogenic genes mediating lipid synthesis. In previous studies, the
      regulation of SREBP-1c mRNA levels by thyroid hormone has remained controversial.
      In this study, we examined whether T3 regulates the mouse SREBP-1c mRNA
      expression. We found that T3 negatively regulates the mouse SREBP-1c gene
      expression in the liver, as shown by ribonuclease protection assays and real-time
      quantitative RT-PCR. Promoter analysis with luciferase assays using HepG2 and
      Hepa1-6 cells revealed that T3 negatively regulates the mouse SREBP-1c gene
      promoter (-574 to +42) and that Site2 (GCCTGACAGGTGAAATCGGC) located around the
      transcriptional start site is responsible for the negative regulation by T3. Gel
      shift assays showed that retinoid X receptor-alpha/thyroid hormone receptor-beta
      heterodimer bound to Site2, but retinoid X receptor-alpha/liver X receptor-
      heterodimer could not bind to the site. In vivo chromatin immunoprecipitation
      assays demonstrated that T3 induced thyroid hormone receptor-beta recruitment to
      Site2. Thus, we demonstrated that mouse SREBP-1c mRNA is down-regulated by T3 in
      vivo and that T3 negatively regulates mouse SREBP-1c gene transcription via a
      novel negative thyroid hormone response element: Site2.

PMID- 16794016
TI  - Increased pro-nerve growth factor and p75 neurotrophin receptor levels in
      developing hypothyroid rat cerebral cortex are associated with enhanced
      apoptosis.
AB  - Thyroid hormone insufficiency adversely affects cortical development; however,
      its effect on apoptosis modulation during cerebral cortex development is not
      understood. We investigated the effect of perinatal hypothyroidism on apoptosis
      and its mechanisms during rat cerebral cortex development. Primary hypothyroidism
      was induced by feeding methimazole (0.025% wt/vol) in the drinking water to
      pregnant and lactating rats and continued until the animals were killed
      (hypothyroid group). Cerebral cortices from pups were harvested at different
      postnatal ages (postnatal d 0, 8, 16, and 24 and adult), and apoptosis was
      quantitated by terminal deoxynucleotide transferase-mediated dUTP nick end
      labeling and cleaved caspase-3 immunoreactivity. Compared with the euthyroid,
      primary somatosensory cortex (S1) in the hypothyroid group exhibited enhanced
      apoptosis. In S1 of euthyroid rats, apoptotic cells were mostly found in cortical
      layers I-III and the proportion of apoptotic cells enhanced significantly in the
      hypothyroid group (P < 0.001). Most of the apoptotic cells were neurons, as
      assessed by double immunolabeling. A significantly increased activation of
      caspase-3 and -7, decreased levels of antiapoptotic proteins Bcl-2 and Bcl-x(L),
      and increased levels of proapoptotic protein Bax was observed in the developing
      cerebral cortex of hypothyroid rats, compared with the euthyroid (P < 0.001). In
      addition, hypothyroidism significantly elevated the levels of 53-kDa pro-nerve
      growth factor (P < 0.001) and p75 neurotrophin receptor (P < 0.001) and decreased
      TrkA expression. Taken together, we provide evidence for the possible
      contribution of pro-nerve growth factor/p75 neurotrophin receptor pathway in
      hypothyroidism-enhanced apoptosis during rat cortical development. Thus, the
      present study may help in explaining the mechanism of the deleterious effect of
      thyroid hormone deficiency on cerebral cortex development in children.

PMID- 16794017
TI  - Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia.
AB  - Our group has developed a rat model of cardiac arrest and cardiopulmonary
      resuscitation (CPR). However, the current rat model uses healthy adult animals.
      In an effort to more closely reproduce the event of cardiac arrest and CPR in
      humans with chronic coronary disease, a rat model of coronary artery constriction
      was investigated during cardiac arrest and CPR. Left coronary artery constriction
      was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley
      rats. Echocardiography was used to measure global cardiac performance before
      surgery and 4 wk postsurgery. Coronary constriction provoked significant
      decreases in ejection fraction, increases in left ventricular end-diastolic
      volume, and increases left ventricular end-systolic volume at 4 wk
      postintervention, just before induction of ventricular fibrillation (VF). After 6
      min of untreated VF, CPR was initiated on three groups: 1) coronary artery
      constriction group, 2) sham-operated group, and 3) control group (without
      preceding surgery). Defibrillation was attempted after 6 min of CPR. All the
      animals were resuscitated. Postresuscitation myocardial function as measured by
      rate of left ventricular pressure increase at 40 mmHg and the rate of left
      ventricular pressure decline was more significantly impaired and left ventricular
      end-diastolic pressure was greater in the coronary artery constriction group
      compared with the sham-operated group and the control group. There were no
      differences in the total shock energy required for successful resuscitation and
      duration of survival among the groups. In summary, this rat model of chronic
      myocardial ischemia was associated with ventricular remodeling and left
      ventricular myocardial dysfunction 4 wk postintervention and subsequently with
      severe postresuscitation myocardial dysfunction. This model would suggest further
      clinically relevant investigation on cardiac arrest and CPR.

PMID- 16794018
TI  - Wavelet analysis of scaling properties of gastric electrical activity.
AB  - We present a novel approach to the analysis of fluctuations in human
      myoelectrical gastric activity measured noninvasively from the surface of the
      abdomen. The time intervals between successive maxima of the wavelet transformed
      quasi-periodic electrogastrographic waveform define the gastric rate variability
      (GRV) time series. By using the method of average wavelet coefficients, the
      statistical fluctuations in the GRV signal in healthy individuals are determined
      to scale in time. Such scaling was previously found in a variety of physiological
      phenomena, all of which support the hypothesis that physiological dynamics
      utilize fractal time series. We determine the scaling index in a cohort of 17
      healthy individuals to be 0.80 +/- 0.14, which compared with a set of surrogate
      data is found to be significant at the level P < 0.01. We also determined that
      the dynamical pattern, so evident in the spectrum of average wavelet coefficients
      of the GRV time series of healthy individuals, is significantly reduced in a
      cohort of systemic sclerosis patients having a scaling index 0.64 +/- 0.17. These
      results imply that the long-term memory in GRV time series is significantly
      reduced from healthy individuals to those with systemic sclerosis. Consequently,
      this disease degrades the complexity of the underlying gastrointestinal control
      system and this degradation is manifest in the loss of scaling in the GRV time
      series.

PMID- 16794019
TI  - Changes in tissue water content measured with multiple-frequency bioimpedance and
      metabolism measured with 31P-MRS during progressive forearm exercise.
AB  - Multiple-frequency bioimpedance analysis (MFBIA) has been used to determine the
      cellular water composition in the human body. It is noninvasive and has
      demonstrated good correlations with other invasive measures of tissue water.
      However, the ability of this method to study transient changes in tissue water in
      specific muscle groups has not been explored. In this study, MFBIA was used to
      assess changes in forearm intracellular water (ICW), extracellular water (ECW),
      and total water (TW) in seven healthy volunteers during and after a progressive
      wrist flexion exercise protocol. In an identical trial, (31)P magnetic resonance
      spectroscopy ((31)P-MRS) was used to assess changes in intracellular pH and
      phosphocreatine (PCr). At the completion of exercise, forearm ICW increased 12.6%
      (SD 0.07, P = 0.003), TW increased 10.1% (SD 0.06, P = 0.005), and no significant
      changes were recorded for ECW. A significant correlation was found between the
      changes in intracellular pH and changes in ICW during exercise (r = -0.84, P =
      0.018). With the use of regression analysis, average changes in P(i), PCr, and pH
      were found to predict changes in ICW (R(2) = 0.98, P = 0.005). In conclusion,
      MFBIA was sensitive enough to measure transient changes in the exercising forearm
      muscle. The changes seen were consistent with the hypothesis that intracellular
      acidification and PCr hydrolysis are important mediators of cellular osmolality
      and therefore may be responsible for the increased volume of water in the
      intracellular space that is often recorded after short-term high-intensity
      exercise.

PMID- 16794020
TI  - Influence of sex steroid hormones on cerebrovascular function.
AB  - The cerebral vasculature is a target tissue for sex steroid hormones. Estrogens,
      androgens, and progestins all influence the function and pathophysiology of the
      cerebral circulation. Estrogen decreases cerebral vascular tone and increases
      cerebral blood flow by enhancing endothelial-derived nitric oxide and
      prostacyclin pathways. Testosterone has opposite effects, increasing cerebral
      artery tone. Cerebrovascular inflammation is suppressed by estrogen but increased
      by testosterone and progesterone. Evidence suggests that sex steroids also
      modulate blood-brain barrier permeability. Estrogen has important protective
      effects on cerebral endothelial cells by increasing mitochondrial efficiency,
      decreasing free radical production, promoting cell survival, and stimulating
      angiogenesis. Although much has been learned regarding hormonal effects on brain
      blood vessels, most studies involve young, healthy animals. It is becoming
      apparent that hormonal effects may be modified by aging or disease states such as
      diabetes. Furthermore, effects of testosterone are complicated because this
      steroid is also converted to estrogen, systemically and possibly within the
      vessels themselves. Elucidating the impact of sex steroids on the cerebral
      vasculature is important for understanding male-female differences in stroke and
      conditions such as menstrual migraine and preeclampsia-related cerebral edema in
      pregnancy. Cerebrovascular effects of sex steroids also need to be considered in
      untangling current controversies regarding consequences of hormone replacement
      therapies and steroid abuse.

PMID- 16794021
TI  - Age-dependent changes in the mechanical properties of tail tendons in TGF-beta
      inducible early gene-1 knockout mice.
AB  - The purpose of this study is to investigate age-dependent changes in the
      architecture and mechanical properties of tendon in TGF-beta inducible early gene
      1 (TIEG) knockout mice. Wild-type and TIEG knockout mice, aged 1, 2, and 15 mo,
      were used. The mechanical properties of tail tendons isolated from these mice
      were determined using uniaxial tensile ramp (0.05 mm/s) and relaxation (5 mm/s)
      tests, with a strain of 10%. Mechanical parameters (Young's modulus from the ramp
      test; fast and static stresses from the relaxation test) were measured and
      recorded. The structure of the tail tendon fascicle was characterized by
      transmission electron microscopy. The results of the mechanical testing revealed
      no significant difference between the knockout and wild-type groups at 1 or 15 mo
      of age. However, the fascicles of the knockout mice at 3 mo of age exhibited
      decreased fast and static stresses compared with those of the wild-type mice.
      Electron microscopy revealed an increase in fibril size in the knockout mouse
      tendons relative to wild-type controls at 1 and 3 mo of age. These data indicate
      an important role for TIEG in tendon microarchitecture and strength in adult
      mice.

PMID- 16794022
TI  - Dyspnea.

PMID- 16794023
TI  - Training adaptations in the behavior of human motor units.
AB  - The purpose of this brief review is to examine the neural adaptations associated
      with training, by focusing on the behavior of single motor units. The review
      synthesizes current understanding on motor unit recruitment and rate coding
      during voluntary contractions, briefly describes the techniques used to record
      motor unit activity, and then evaluates the adaptations that have been observed
      in motor unit activity during maximal and submaximal contractions. Relatively few
      studies have directly compared motor unit behavior before and after training.
      Although some studies suggest that the voluntary activation of muscle can
      increase slightly with strength training, it is not known how the discharge of
      motor units changes to produce this increase in activation. The evidence
      indicates that the increase is not attributable to changes in motor unit
      synchronization. It has been demonstrated, however, that training can increase
      both the rate of torque development and the discharge rate of motor units.
      Furthermore, both strength training and practice of a force-matching task can
      evoke adaptations in the discharge characteristics of motor units. Because the
      variability in discharge rate has a significant influence on the fluctuations in
      force during submaximal contractions, the changes produced with training can
      influence motor performance during activities of daily living. Little is known,
      however, about the relative contributions of the descending drive, afferent
      feedback, spinal circuitry, and motor neuron properties to the observed
      adaptations in motor unit activity.

PMID- 16794024
TI  - Reversibility of exercise-induced dendritic attenuation in brain
      cardiorespiratory and locomotor areas following exercise detraining.
AB  - It has been shown previously that dendritic branching in cardiorespiratory and
      locomotor brain areas can be attenuated with exercise training (ET). It was not
      known whether this process was reversible. Twenty-three (n = 23) male Sprague
      Dawley rats were individually caged and divided into two groups: untrained (UN; n
      = 11) and detrained (DTR; n = 12). DTR were provided with a running wheel at 21
      days of age and exercised spontaneously. After 120 days (70 days of ET followed
      by 50 days of detraining), ET indexes were obtained, including maximal oxygen
      uptake, percent body fat, resting heart rate, and heart weight-to-body weight
      ratios. The brain was processed according to a modified Golgi-Cox procedure.
      Impregnated neurons from the periaqueductal gray (PAG), posterior hypothalamic
      area (PH), nucleus of the tractus solitarius (NTS), and cuneiform nucleus (CfN)
      were examined in coronal sections. Neurons were traced using a camera lucida
      technique and analyzed using the Sholl concentric ring analysis of dendritic
      branching. t-Tests compared the mean number of intersections per neuron by
      grouping inner rings, outer rings, and total number of intersections per animal.
      There were no significant differences between UN and DTR in PH, PAG, CfN, and NTS
      in the inner rings, outer rings, and total number of intersections per animal. A
      separate group of animals was used to show that a training effect in the CfN and
      NTS was present at 56 days of ET. Our results show that dendritic attenuation
      resulting from 70 days of ET in PH, PAG, CfN, and NTS is completely reversed with
      50 days of detraining.

PMID- 16794025
TI  - MCA Vmean and the arterial lactate-to-pyruvate ratio correlate during rhythmic
      handgrip.
AB  - Regulation of cerebral blood flow during physiological activation including
      exercise remains unknown but may be related to the arterial lactate-to-pyruvate
      (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral
      artery mean velocity (MCA Vmean) relates to the arterial L/P ratio at two plasma
      lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at
      rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal
      voluntary contraction force, and during 20 min of recovery in seven healthy male
      volunteers during control and a approximately 15 mmol/l hyperglycemic clamp.
      Cerebral arteriovenous differences for metabolites were obtained by brachial
      artery and retrograde jugular venous catheterization. Control resting arterial
      lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0
      micromol/l (L/P ratio 16.4 +/- 1.0) with a corresponding MCA Vmean of 46.7 +/-
      4.5 cm/s. During rhythmic handgrip the increase in MCA Vmean to 51.2 +/- 4.6 cm/s
      was related to the increased L/P ratio (23.8 +/- 2.5; r2 = 0.79; P < 0.01).
      Hyperglycemia increased arterial lactate and pyruvate to 1.9 +/- 0.2 mmol/l and
      115 +/- 4 micromol/l, respectively, but it did not significantly influence the
      L/P ratio or MCA Vmean at rest or during exercise. Conversely, MCA Vmean did not
      correlate significantly, neither to the arterial lactate nor to the pyruvate
      concentrations. These results support that the arterial plasma L/P ratio
      modulates cerebral blood flow during cerebral activation independently from the
      plasma glucose concentration.

PMID- 16794026
TI  - Effect of caffeine supplementation on the extracellular heat shock protein 72
      response to exercise.
AB  - The stimulus for the release of 72-kDa heat shock protein (HSP72) during exercise
      in humans is currently unclear. Recent evidence in an animal model is suggestive
      of an involvement of catecholamines. The present study, therefore, investigated
      the effect of caffeine supplementation, a known stimulator of sympathetic
      activity, on the extracellular (e)HSP72 response to prolonged exercise. Ten
      healthy male endurance-trained cyclists were recruited (age: 21 +/- 1 yr, maximum
      O(2) uptake 61.1 +/- 1.7 ml x kg(-1) x min(-1), mean +/- SE). Each subject was
      randomly assigned to ingest either 6 mg/kg body mass of caffeine (Caff) or
      placebo (Pla) 60 min before one of two 90-min bouts of cycling at 74 +/- 1%
      maximum O(2) uptake. Trials were performed at least 7 days apart in a
      counterbalanced design. Venous blood samples were collected by venepuncture at
      pretreatment, preexercise, postexercise, and 1 h postexercise. Serum caffeine and
      plasma catecholamines were determined using a spectrophotometric assay and high
      performance liquid chromatography, respectively. Plasma HSP72 and cortisol were
      determined by ELISA. Serum caffeine concentrations were significantly increased
      throughout Caff, while no increases were detected in Pla. Caffeine
      supplementation and exercise was associated with a greater eHSP72 response than
      exercise alone (postexercise Caff 8.6 +/- 1.3 ng/ml; Pla 5.9 +/- 0.9 ng/ml). This
      greater eHSP72 response was associated with a greater epinephrine response to
      exercise in Caff. There was a significant increase in norepinephrine and
      cortisol, with no intertrial differences. The present data suggest that, in
      humans, catecholamines may be an important mediator of the exercise-induced
      increase in eHSP72 concentration.

PMID- 16794027
TI  - Postnatal developmental changes in CO2 sensitivity in rats.
AB  - Ventilatory sensitivity to CO(2) in awake adult Brown Norway (BN) rats is 50-75%
      lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The
      purpose of the present study was to test the hypothesis that this difference
      would be apparent during the development of CO(2) sensitivity. Four litters of
      each strain were divided into four groups such that rats were exposed to 7%
      inspired CO(2) for 5 min in a plethysmograph every third day from postnatal day
      (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO(2) exposure increased
      pulmonary ventilation (Ve) by 25-50% in the BN and SD strains and between 25 to
      over 200% in the SS strain. In all strains beginning around P15, the response to
      CO(2) increased progressively reaching a peak at P19-21 when Ve during
      hypercapnia was 175-225% above eucapnia. There were minimal changes in CO(2)
      sensitivity between P21 and P30, and at both ages there were minimal between
      strain differences. At P30, the response to CO(2) in the SS and SD strains was
      near the adult response, but the response in the BN rats was 100% greater at P30
      than in adults. We conclude that 1) CO(2)-sensing mechanisms, and/or mechanisms
      downstream from the chemoreceptors, change dramatically at the age in rats when
      other physiological systems are also maturing ( approximately P15), and 2) there
      is a high degree of age-dependent plasticity in CO(2) sensitivity in rats, which
      differs between strains.

PMID- 16794028
TI  - Increased serum erythropoietin but not red cell production after 4 wk of
      intermittent hypobaric hypoxia (4,000-5,500 m).
AB  - This study tested the hypothesis that athletes exposed to 4 wk of intermittent
      hypobaric hypoxia exposure (3 h/day, 5 days/wk at 4,000-5,500 m) or double-blind
      placebo increase their red blood cell volume (RCV) and hemoglobin mass (Hbmass)
      secondary to an increase in erythropoietin (EPO). Twenty-three collegiate level
      athletes were measured before (Pre) and after (Post) the intervention for RCV via
      Evans blue (EB) dye and in duplicate for Hbmass using CO rebreathing.
      Hematological indexes including EPO, soluble transferrin receptor, and
      reticulocyte parameters were measured on 8-10 occasions spanning the
      intervention. The subjects were randomly divided among hypobaric hypoxia (Hypo, n
      = 11) and normoxic (Norm, n = 12) groups. Apart from doubling EPO concentration 3
      h after hypoxia there was no increase in any of the measures for either Hypo or
      Norm groups. The mean change in RCV from Pre to Post for the Hypo group was 2.3%
      (95% confidence limits = -4.8 to 9.5%) and for the Norm group was -0.2% (-5.7 to
      5.3%). The corresponding changes in Hbmass were 1.0% (-1.3 to 3.3%) for Hypo and 
      0.3% (-2.6 to 3.1%) for Norm. There was good agreement between blood volume (BV)
      from EB and CO: EB BV = 1.03 x CO BV + 142, r2 = 0.85, P < 0.0001. Overall,
      evidence from four independent techniques (RCV, Hbmass, reticulocyte parameters,
      and soluble transferrin receptor) suggests that intermittent hypobaric hypoxia
      exposure did not accelerate erythropoiesis despite the increase in serum EPO.

PMID- 16794029
TI  - The mRNA expression profile of metabolic genes relative to MHC isoform pattern in
      human skeletal muscles.
AB  - The metabolic profile of rodent muscle is generally reflected in the myosin heavy
      chain (MHC) fiber-type composition. The present study was conducted to test the
      hypothesis that metabolic gene expression is not tightly coupled with MHC fiber
      type composition for all genes in human skeletal muscle. Triceps brachii, vastus
      lateralis quadriceps, and soleus muscle biopsies were obtained from normally
      physically active, healthy, young male volunteers, because these muscles are
      characterized by different fiber-type compositions. As expected, citrate synthase
      and 3-hydroxyacyl dehydrogenase activity was more than twofold higher in soleus
      and vastus than in triceps. Contrary, phosphofructokinase and total lactate
      dehydrogenase (LDH) activity was approximately three- and twofold higher in
      triceps than in both soleus and vastus. Expression of metabolic genes was
      assessed by determining the mRNA content of a broad range of metabolic genes. The
      triceps muscle had two- to fivefold higher MHC IIa, phosphofructokinase, and LDH
      A mRNA content and two- to fourfold lower MHC I, lipoprotein lipase, CD36,
      hormone-sensitive lipase, and LDH B and hexokinase II mRNA than vastus lateralis
      or soleus. Interestingly, such mRNA differences were not evident for any of the
      genes encoding mitochondrial oxidative proteins, 3-hydroxyacyl dehydrogenase,
      carnitine palmitoyl transferase I, citrate synthase, alpha-ketogluterate
      dehydrogenase, and cytochrome c, nor for the transcriptional regulators
      peroxisome proliferator activator receptor gamma coactivator-1alpha, forkhead box
      O1, or peroxisome proliferator activator receptor-alpha. Thus the mRNA expression
      of genes encoding mitochondrial proteins and transcriptional regulators does not
      seem to be fiber type specific as the genes encoding glycolytic and lipid
      metabolism genes, which suggests that basal mRNA regulation of genes encoding
      mitochondrial proteins does not match the wide differences in mitochondrial
      content of these muscles.

PMID- 16794030
TI  - A WNTer wonderland in Snowbird.
AB  - The Keystone Symposium on ;Wnt and beta-catenin signaling in development and
      disease' was held recently in Snowbird, UT, USA. Organized by Mariann Bienz and
      Hans Clevers, this meeting covered a wide range of topics, including Wnt protein
      biogenesis, Wnt receptors and signaling pathways, beta-catenin/Tcf complexes and
      gene expression, Wnt signaling in development, cancer, stem cell biology and
      regeneration, and therapeutics that target the Wnt/beta-catenin pathway.

PMID- 16794031
TI  - JAK/STAT signalling in Drosophila: insights into conserved regulatory and
      cellular functions.
AB  - High levels of interspecies conservation characterise all signal transduction
      cascades and demonstrate the significance of these pathways over evolutionary
      time. Here, we review advances in the field of JAK/STAT signalling, focusing on
      recent developments in Drosophila. In particular, recent results from genetic and
      genome-wide RNAi screens, as well as studies into the developmental roles played
      by this pathway, highlight striking levels of physical and functional
      conservation in processes such as cellular proliferation, immune responses and
      stem cell maintenance. These insights underscore the value of model organisms for
      improving our understanding of this human disease-relevant pathway.

PMID- 16794032
TI  - Coordinated cell-shape changes control epithelial movement in zebrafish and
      Drosophila.
AB  - Epithelial morphogenesis depends on coordinated changes in cell shape, a process
      that is still poorly understood. During zebrafish epiboly and Drosophila dorsal
      closure, cell-shape changes at the epithelial margin are of critical importance.
      Here evidence is provided for a conserved mechanism of local actin and myosin 2
      recruitment during theses events. It was found that during epiboly of the
      zebrafish embryo, the movement of the outer epithelium (enveloping layer) over
      the yolk cell surface involves the constriction of marginal cells. This process
      depends on the recruitment of actin and myosin 2 within the yolk cytoplasm along
      the margin of the enveloping layer. Actin and myosin 2 recruitment within the
      yolk cytoplasm requires the Ste20-like kinase Msn1, an orthologue of Drosophila
      Misshapen. Similarly, in Drosophila, actin and myosin 2 localization and cell
      constriction at the margin of the epidermis mediate dorsal closure and are
      controlled by Misshapen. Thus, this study has characterized a conserved mechanism
      underlying coordinated cell-shape changes during epithelial morphogenesis.

PMID- 16794033
TI  - Dynamic redistribution of vasa homolog and exclusion of somatic cell determinants
      during germ cell specification in Ciona intestinalis.
AB  - Ascidian embryos sequester a specific cytoplasm, called the postplasm, at the
      posterior pole, where many maternal RNAs and proteins accumulate. Although the
      postplasm is thought to act as the germ plasm, it is also highly enriched in
      several factors essential for somatic cell development, and how the postplasm
      components regulate both germ and somatic cell differentiation remains elusive.
      Using a vasa homolog, CiVH, and other postplasmic components as markers, we found
      that the postplasm-containing blastomeres, the B7.6 cells, undergo an asymmetric
      cell division during gastrulation to produce two distinct daughter cells: B8.11
      and B8.12. Most of the postplasmic components segregate only into the B8.11
      cells, which never coalesce into the gonad. By contrast, the maternal CiVH RNA
      and protein are specifically distributed into the B8.12 cells, which divide
      further and are incorporated into the gonad in juveniles. In the B8.12 cells,
      CiVH production is upregulated from the maternal RNA source, resulting in the
      formation of perinuclear CiVH granules, which may be the nuage, a hallmark of
      germ cells in many animal species. We propose that the redistribution of specific
      maternal molecules into the B8.12 cells is essential for germ-cell specification
      in ascidians.

PMID- 16794034
TI  - Discordant developmental waves of angioblasts and hemangioblasts in the early
      gastrulating mouse embryo.
AB  - Vasculogenesis and hematopoiesis are thought to arise in hemangioblasts, the
      common progenitors of cells in vessels and in blood. This scheme was challenged
      by kinetic analysis of vascular endothelial and hematopoietic progenitors in
      early gastrulating mouse embryos. The OP-9 co-culture system with a combination
      of cytokines permitted the detection of endothelial progenitors, as well as
      stroma-dependent hematopoietic progenitors. Endothelial progenitors were detected
      as early as embryonic day (E) 5.50, after which time their numbers increased.
      Stroma-dependent hematopoietic progenitors were detected at E6.75, the time point
      when hemangioblasts reportedly emerge. Colony-forming units in culture (CFU-c),
      most likely generated from stroma-dependent hematopoietic progenitors via contact
      with the microenvironment, were detected at E7.50, concomitant with the onset of
      primitive hematopoiesis in the yolk sac. The presence of nucleated erythrocytes
      and the expression of an embryonic-type globin in erythroid colonies derived from
      stroma-dependent hematopoietic progenitors and from CFU-c support the notion that
      these progenitors coordinately establish primitive hematopoiesis. Using Oct3/4
      promoter-driven GFP transgenic mice, early endothelial progenitors, stroma
      dependent hematopoietic progenitors, and CFU-c were all shown to express the
      Oct3/4 transcription factor. Among Oct3/4-positive cells, both endothelial and
      hematopoietic progenitors were present in the CD31-positive fraction, leaving a
      subset of endothelial progenitors in the CD31-negative fraction. These data imply
      that Oct3/4-positive mesoderm gives rise to CD31-negative angioblasts, CD31
      positive angiboblasts and CD31-positive hemangioblasts. We propose a distinct
      developmental pathway in which the angioblast lineage directly diverges from
      mesoderm prior to and independent of hemangioblast development.

PMID- 16794035
TI  - The measure of man.

PMID- 16794036
TI  - Management of osteochondritis dissecans of the knee: current concepts review.
AB  - Osteochondritis dissecans of the knee is being seen with increased frequency in
      pediatric and young adult athletes and is thought to be, in part, owing to
      earlier and increasingly competitive sports participation. Despite much
      speculation, the cause of both juvenile and adult osteochondritis dissecans
      remains unclear. Early recognition is essential. Whereas adult osteochondritis
      dissecans lesions have a greater propensity to instability, juvenile
      osteochondritis dissecans lesions are typically stable, and those with an intact
      articular surface have a potential to heal with nonoperative treatment through
      cessation of repetitive impact loading. The value of adjunctive immobilization,
      protected weightbearing, and unloader bracing has not been established.
      Skeletally immature patients with stable lesions that have not healed with
      nonoperative treatment should have consideration given to arthroscopic drilling
      to promote healing before the lesion progresses and requires more involved
      treatment with a less optimistic prognosis. Magnetic resonance imaging may allow
      early prediction of lesion healing potential. The majority of adult
      osteochondritis dissecans cases as well as those skeletally immature patients
      with unstable lesions and secondary loose bodies require fixation and possible
      bone grafting. Many unstable lesions will heal after stabilization, but long-term
      prognosis is not clear. Chronic loose fragments can be difficult to fix and have
      poor healing potential. Results of excision of large lesions from weightbearing
      zones are poor. Chondral resurfacing techniques have limited long-term data for
      cases of osteochondritis dissecans in skeletally immature patients.

PMID- 16794037
TI  - A clamping mechanism involved in SNARE-dependent exocytosis.
AB  - During neurotransmitter release at the synapse, influx of calcium ions stimulates
      the release of neurotransmitter. However, the mechanism by which synaptic vesicle
      fusion is coupled to calcium has been unclear, despite the identification of both
      the core fusion machinery [soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor (SNARE)] and the principal calcium sensor (synaptotagmin). Here,
      we describe what may represent a basic principle of the coupling mechanism: a
      reversible clamping protein (complexin) that can freeze the SNAREpin, an
      assembled fusion-competent intermediate en route to fusion. When calcium binds to
      the calcium sensor synaptotagmin, the clamp would then be released. SNARE
      proteins, and key regulators like synaptotagmin and complexin, can be ectopically
      expressed on the cell surface. Cells expressing such "flipped" synaptic SNAREs
      fuse constitutively, but when we coexpressed complexin, fusion was blocked.
      Adding back calcium triggered fusion from this intermediate in the presence of
      synaptotagmin.

PMID- 16794038
TI  - Plio-Pleistocene ice volume, Antarctic climate, and the global delta18O record.
AB  - We propose that from approximately 3 to 1 million years ago, ice volume changes
      occurred in both the Northern and Southern Hemispheres, each controlled by local
      summer insolation. Because Earth's orbital precession is out of phase between
      hemispheres, 23,000-year changes in ice volume in each hemisphere cancel out in
      globally integrated proxies such as ocean delta18O or sea level, leaving the in
      phase obliquity (41,000 years) component of insolation to dominate those records.
      Only a modest ice mass change in Antarctica is required to effectively cancel out
      a much larger northern ice volume signal. At the mid-Pleistocene transition, we
      propose that marine-based ice sheet margins replaced terrestrial ice margins
      around the perimeter of East Antarctica, resulting in a shift to in-phase
      behavior of northern and southern ice sheets as well as the strengthening of
      23,000-year cyclicity in the marine delta18O record.

PMID- 16794040
TI  - Arginylation of beta-actin regulates actin cytoskeleton and cell motility.
AB  - Posttranslational arginylation is critical for mouse embryogenesis,
      cardiovascular development, and angiogenesis, but its molecular effects and the
      identity of proteins arginylated in vivo are unknown. We found that beta-actin
      was arginylated in vivo to regulate actin filament properties, beta-actin
      localization, and lamella formation in motile cells. Arginylation of beta-actin
      apparently represents a critical step in the actin N-terminal processing needed
      for actin functioning in vivo. Thus, posttranslational arginylation of a single
      protein target can regulate its intracellular function, inducing global changes
      on the cellular level, and may contribute to cardiovascular development and
      angiogenesis.

PMID- 16794041
TI  - Early Pleistocene glacial cycles and the integrated summer insolation forcing.
AB  - Long-term variations in Northern Hemisphere summer insolation are generally
      thought to control glaciation. But the intensity of summer insolation is
      primarily controlled by 20,000-year cycles in the precession of the equinoxes,
      whereas early Pleistocene glacial cycles occur at 40,000-year intervals, matching
      the period of changes in Earth's obliquity. The resolution of this 40,000-year
      problem is that glaciers are sensitive to insolation integrated over the duration
      of the summer. The integrated summer insolation is primarily controlled by
      obliquity and not precession because, by Kepler's second law, the duration of the
      summer is inversely proportional to Earth's distance from the Sun.

PMID- 16794042
TI  - Biodiversity research still grounded.

PMID- 16794039
TI  - Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in
      Parkinson's models.
AB  - Alpha-synuclein (alphaSyn) misfolding is associated with several devastating
      neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells
      and in neurons alphaSyn accumulation is cytotoxic, but little is known about its
      normal function or pathobiology. The earliest defect following alphaSyn
      expression in yeast was a block in endoplasmic reticulum (ER)-to-Golgi vesicular
      trafficking. In a genomewide screen, the largest class of toxicity modifiers were
      proteins functioning at this same step, including the Rab guanosine
      triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions.
      Elevated expression of Rab1, the mammalian YPT1 homolog, protected against
      alphaSyn-induced dopaminergic neuron loss in animal models of PD. Thus,
      synucleinopathies may result from disruptions in basic cellular functions that
      interface with the unique biology of particular neurons to make them especially
      vulnerable.

PMID- 16794043
TI  - Volcanology. Scientists steal a daring look at Merapi's explosive potential.

PMID- 16794044
TI  - Influenza. What came before 1918? Archaeovirologist offers a first glimpse.

PMID- 16794045
TI  - Psychology. The value of the stick: punishment was a driver of altruism.

PMID- 16794046
TI  - Research ethics. China's science ministry fires a barrage of measures at
      misconduct.

PMID- 16794047
TI  - National Science Foundation. House panel tells NSF to keep eye on the prize.

PMID- 16794048
TI  - 2007 NASA budget. Space scientists score a modest victory in House spending bill.

PMID- 16794049
TI  - Evolution. Spider genes and fossils spin tales of the original worldwide web.

PMID- 16794050
TI  - Species conservation. A 'forever' seed bank takes root in the Arctic.

PMID- 16794052
TI  - Seismology. The strain builds in southern California.

PMID- 16794051
TI  - Archaeology. First jewelry? Old shell beads suggest early use of symbols.

PMID- 16794053
TI  - European science. E.U. Parliament approves funding for human ES cells.

PMID- 16794054
TI  - U.S. bioethics. House panel finds fault with how NIH handles tissue samples.

PMID- 16794055
TI  - Animal cognition. Social animals prove their smarts.

PMID- 16794057
TI  - Paleoanthropology. A rare meeting of the minds.

PMID- 16794056
TI  - Animal cognition. Man's best friend(s) reveal the possible roots of social
      intelligence.

PMID- 16794058
TI  - Paleoanthropology. Paleoanthropology's unsung hero.

PMID- 16794059
TI  - Looking at biofuels and bioenergy.

PMID- 16794060
TI  - Measuring the efficiency of biomass energy.

PMID- 16794061
TI  - Harvesting our meadows for biofuel?

PMID- 16794062
TI  - Energy returns on ethanol production.

PMID- 16794063
TI  - Caution on nominee to head USGS.

PMID- 16794064
TI  - Comment on "Nature of phosphorus limitation in the ultraoligotrophic eastern
      Mediterranean".
AB  - Thingstad et al. (Reports, 12 August 2005, p. 1068) reported that in situ
      mesoscale phosphorus enrichment of the eastern Mediterranean Sea altered selected
      biological parameters and concluded that the added phosphorus was rapidly
      transferred from bacteria to mesozooplankton. However, because of a lack of
      replication and a misinterpretation of their statistical analyses, that
      conclusion is not supported by the data.

PMID- 16794065
TI  - Ecology. Coral reefs and the global network of Marine Protected Areas.

PMID- 16794067
TI  - Planetary science. Our local astrophysical laboratory.

PMID- 16794066
TI  - Transcription. Gene expression needs a break to unwind before carrying on.

PMID- 16794068
TI  - Climate change. Threats to water supplies in the tropical Andes.

PMID- 16794069
TI  - Cell signaling. A new way to burn fat.

PMID- 16794070
TI  - Oceanography. A direct proxy for oceanic phosphorus?

PMID- 16794071
TI  - Astronomy. Very energetic gamma-rays from microquasars and binary pulsars.

PMID- 16794072
TI  - Early Cretaceous spider web with its prey.
AB  - The orb web is a spectacular evolutionary innovation that enables spiders to
      catch flying prey. This elegant, geometric structure is woven with silk fibers
      that are renowned for their superior mechanical properties. We used silk gland
      expression libraries to address a long-standing controversy concerning the
      evolution of the orb-web architecture. Contrary to the view that the orb-web
      design evolved multiple times, we found that the distribution and phylogeny of
      silk proteins support a single, ancient origin of the orb web at least 136
      million years ago. Furthermore, we substantially expanded the repository of silk
      sequences that can be used for the synthesis of high-performance biomaterials.

PMID- 16794073
TI  - Silk genes support the single origin of orb webs.
AB  - The orb web is a spectacular evolutionary innovation that enables spiders to
      catch flying prey. This elegant, geometric structure is woven with silk fibers
      that are renowned for their superior mechanical properties. We used silk gland
      expression libraries to address a long-standing controversy concerning the
      evolution of the orb-web architecture. Contrary to the view that the orb-web
      design evolved multiple times, we found that the distribution and phylogeny of
      silk proteins support a single, ancient origin of the orb web at least 136
      million years ago. Furthermore, we substantially expanded the repository of silk
      sequences that can be used for the synthesis of high-performance biomaterials.

PMID- 16794074
TI  - TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism.
AB  - During fasting, increased concentrations of circulating catecholamines promote
      the mobilization of lipid stores from adipose tissue in part by phosphorylating
      and inactivating acetyl-coenzyme A carboxylase (ACC), the rate-limiting enzyme in
      fatty acid synthesis. Here, we describe a parallel pathway, in which the
      pseudokinase Tribbles 3 (TRB3), whose abundance is increased during fasting,
      stimulates lipolysis by triggering the degradation of ACC in adipose tissue. TRB3
      promoted ACC ubiquitination through an association with the E3 ubiquitin ligase
      constitutive photomorphogenic protein 1 (COP1). Indeed, adipocytes deficient in
      TRB3 accumulated larger amounts of ACC protein than did wild-type cells. Because
      transgenic mice expressing TRB3 in adipose tissue are protected from diet-induced
      obesity due to enhanced fatty acid oxidation, these results demonstrate how
      phosphorylation and ubiquitination pathways converge on a key regulator of lipid
      metabolism to maintain energy homeostasis.

PMID- 16794075
TI  - Costly punishment across human societies.
AB  - Recent behavioral experiments aimed at understanding the evolutionary foundations
      of human cooperation have suggested that a willingness to engage in costly
      punishment, even in one-shot situations, may be part of human psychology and a
      key element in understanding our sociality. However, because most experiments
      have been confined to students in industrialized societies, generalizations of
      these insights to the species have necessarily been tentative. Here, experimental
      results from 15 diverse populations show that (i) all populations demonstrate
      some willingness to administer costly punishment as unequal behavior increases,
      (ii) the magnitude of this punishment varies substantially across populations,
      and (iii) costly punishment positively covaries with altruistic behavior across
      populations. These findings are consistent with models of the gene-culture
      coevolution of human altruism and further sharpen what any theory of human
      cooperation needs to explain.

PMID- 16794076
TI  - Middle Paleolithic shell beads in Israel and Algeria.
AB  - Perforated marine gastropod shells at the western Asian site of Skhul and the
      North African site of Oued Djebbana indicate the early use of beads by modern
      humans in these regions. The remoteness of these sites from the seashore and a
      comparison of the shells to natural shell assemblages indicate deliberate
      selection and transport by humans for symbolic use. Elemental and chemical
      analyses of sediment matrix adhered to one Nassarius gibbosulus from Skhul
      indicate that the shell bead comes from a layer containing 10 human fossils and
      dating to 100,000 to 135,000 years ago, about 25,000 years earlier than previous
      evidence for personal decoration by modern humans in South Africa.

PMID- 16794077
TI  - Phosphorus in cold-water corals as a proxy for seawater nutrient chemistry.
AB  - Phosphorus is a key macronutrient being strongly enriched in the deep ocean as a
      result of continuous export and remineralization of biomass from primary
      production. We show that phosphorus incorporated within the skeletons of the
      cosmopolitan cold-water coral Desmophyllum dianthus is directly proportional to
      the ambient seawater phosphorus concentration and thus may serve as a paleo
      oceanographic proxy for variations in ocean productivity as well as changes in
      the residence times and sources of deep-water masses. The application of this
      tool to fossil specimens from the Mediterranean reveals phosphorus-enriched
      bottom waters at the end of the Younger Dryas period.

PMID- 16794078
TI  - Metagenomic analysis of coastal RNA virus communities.
AB  - RNA viruses infect marine organisms from bacteria to whales, but RNA virus
      communities in the sea remain essentially unknown. Reverse-transcribed whole
      genome shotgun sequencing was used to characterize the diversity of uncultivated
      marine RNA virus assemblages. A diverse assemblage of RNA viruses, including a
      broad group of marine picorna-like viruses, and distant relatives of viruses
      infecting arthropods and higher plants were found. Communities were dominated by
      distinct genotypes with small genome sizes, and we completely assembled the
      genomes of several hitherto undiscovered viruses. Our results show that the
      oceans are a reservoir of previously unknown RNA viruses.

PMID- 16794079
TI  - A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription.
AB  - Multiple enzymatic activities are required for transcriptional initiation. The
      enzyme DNA topoisomerase II associates with gene promoter regions and can
      generate breaks in double-stranded DNA (dsDNA). Therefore, it is of interest to
      know whether this enzyme is critical for regulated gene activation. We report
      that the signal-dependent activation of gene transcription by nuclear receptors
      and other classes of DNA binding transcription factors, including activating
      protein 1, requires DNA topoisomerase IIbeta-dependent, transient, site-specific
      dsDNA break formation. Subsequent to the break, poly(adenosine diphosphate
      ribose) polymerase-1 enzymatic activity is induced, which is required for a
      nucleosome-specific histone H1-high-mobility group B exchange event and for local
      changes of chromatin architecture. Our data mechanistically link DNA
      topoisomerase IIbeta-dependent dsDNA breaks and the components of the DNA damage
      and repair machinery in regulated gene transcription.

PMID- 16794080
TI  - The muscle protein Dok-7 is essential for neuromuscular synaptogenesis.
AB  - The formation of the neuromuscular synapse requires muscle-specific receptor
      kinase (MuSK) to orchestrate postsynaptic differentiation, including the
      clustering of receptors for the neurotransmitter acetylcholine. Upon innervation,
      neural agrin activates MuSK to establish the postsynaptic apparatus, although
      agrin-independent formation of neuromuscular synapses can also occur
      experimentally in the absence of neurotransmission. Dok-7, a MuSK-interacting
      cytoplasmic protein, is essential for MuSK activation in cultured myotubes; in
      particular, the Dok-7 phosphotyrosine-binding domain and its target in MuSK are
      indispensable. Mice lacking Dok-7 formed neither acetylcholine receptor clusters
      nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular
      synaptogenesis through its interaction with MuSK.

PMID- 16794081
TI  - Depletion, degradation, and recovery potential of estuaries and coastal seas.
AB  - Estuarine and coastal transformation is as old as civilization yet has
      dramatically accelerated over the past 150 to 300 years. Reconstructed time
      lines, causes, and consequences of change in 12 once diverse and productive
      estuaries and coastal seas worldwide show similar patterns: Human impacts have
      depleted >90% of formerly important species, destroyed >65% of seagrass and
      wetland habitat, degraded water quality, and accelerated species invasions.
      Twentieth-century conservation efforts achieved partial recovery of upper trophic
      levels but have so far failed to restore former ecosystem structure and function.
      Our results provide detailed historical baselines and quantitative targets for
      ecosystem-based management and marine conservation.

PMID- 16794082
TI  - JETLAG resets the Drosophila circadian clock by promoting light-induced
      degradation of TIMELESS.
AB  - Organisms ranging from bacteria to humans synchronize their internal clocks to
      daily cycles of light and dark. Photic entrainment of the Drosophila clock is
      mediated by proteasomal degradation of the clock protein TIMELESS (TIM). We have
      identified mutations in jetlag-a gene coding for an F-box protein with leucine
      rich repeats-that result in reduced light sensitivity of the circadian clock.
      Mutant flies show rhythmic behavior in constant light, reduced phase shifts in
      response to light pulses, and reduced light-dependent degradation of TIM.
      Expression of JET along with the circadian photoreceptor cryptochrome (CRY) in
      cultured S2R cells confers light-dependent degradation onto TIM, thereby
      reconstituting the acute response + of the circadian clock to light in a cell
      culture system. Our results suggest that JET is essential for resetting the clock
      by transmitting light signals from CRY to TIM.

PMID- 16794083
TI  - The ophthalmo-meningeal foramen masquerading as an intraocular foreign body.
AB  - Although the diagnosis of intraocular foreign body is primarily a clinical one,
      radiographic imaging is often used to clarify the diagnosis and to localise the
      foreign body. For this case the radiographic findings served to confuse the
      diagnosis.

PMID- 16794084
TI  - Tick paralysis with atypical presentation: isolated, reversible involvement of
      the upper trunk of brachial plexus.
AB  - Tick paralysis is a disease that occurs worldwide. It is a relatively rare but
      potentially fatal condition. The only way to establish the diagnosis is to
      carefully search for the tick paralysis. It is caused by a neurotoxin secreted by
      engorged female ticks. Tick paralysis generally begins in the lower extremities
      and ascends symmetrically to involve the trunk, upper extremities and head within
      a few hours. Although early-onset prominent bulbar palsy and isolated facial
      weakness without generalised paralysis are rare, there is no report in the
      English literature concerning isolated, reversible involvement of the upper trunk
      of brachial plexus caused by tick bite. We report a case of isolated, reversible
      involvement of the upper trunk of brachial plexus as a variant of tick paralysis.
      Diagnosis was confirmed with needle electromyography and nerve conduction
      examination. Within 2 weeks, the patient was fully recovered. The purpose of
      presenting this case is to remind clinicians that tick paralysis should be
      considered even in cases with atypical neurological findings admitted to the
      emergency department.

PMID- 16794085
TI  - Car seat palsy.
AB  - Soft tissue trauma causing peripheral paralysis of the facial nerve is a rarely
      described event in children. The author describes such a case where a boy
      developed paralysis of the buccal division of the facial nerve in the absence of
      any bony injury, through collision with the cushioned side of a child seat during
      a road traffic accident. He had no other injuries. This reinforces the importance
      of thorough clinical examination in the detection of subtle neurological
      abnormalities in young children.

PMID- 16794086
TI  - Cerebral venous sinus thrombosis presenting in the puerperium.

PMID- 16794087
TI  - Out of hours care in the community; a shambles or work in progress?

PMID- 16794088
TI  - Is hot water immersion an effective treatment for marine envenomation?
AB  - Envenomation by marine creatures is common. As more people dive and snorkel for
      leisure, the incidence of envenomation injuries presenting to emergency
      departments has increased. Although most serious envenomations occur in the
      temperate or tropical waters of the Indo-Pacific region, North American and
      European waters also provide a habitat for many stinging creatures. Marine
      envenomations can be classified as either surface stings or puncture wounds.
      Antivenom is available for a limited number of specific marine creatures. Various
      other treatments such as vinegar, fig juice, boiled cactus, heated stones, hot
      urine, hot water, and ice have been proposed, although many have little
      scientific basis. The use of heat therapies, previously reserved for penetrating
      fish spine injuries, has been suggested as treatment for an increasing variety of
      marine envenomation. This paper reviews the evidence for the effectiveness of hot
      water immersion (HWI) and other heat therapies in the management of patients
      presenting with pain due to marine envenomation.

PMID- 16794089
TI  - A structured literature review on the use of high fidelity patient simulators for
      teaching in emergency medicine.
AB  - High fidelity simulators are commonly used educational tools, mainly in
      anaesthesia. This literature review examines the use of simulators for teaching
      in emergency medicine and covers some of their advantages and disadvantages, and
      evidence for their use.

PMID- 16794090
TI  - Accident and emergency training perspectives in Scotland.
AB  - OBJECTIVE: To determine the perspectives of Scottish accident and emergency (A&E)
      trainees and trainers on current training in the speciality, in order to help
      develop a simulator based training programme to complement existing training.
      METHODS: Questionnaires were sent to all Scottish A&E trainees and consultants
      responsible for training. They were presented with various clinical challenges.
      Trainees were asked to rate their confidence, experience, knowledge, and training
      on a Likert scale of 1 to 5. Trainers were asked to identify those areas where
      they felt trainees' performance consistently failed to meet a desired standard,
      and whether this was the result of lack of training, lack of exposure, or both.
      RESULTS: Trainees' response rate was 75%; consultants' was 59.4%. Overall
      trainees gave scores of 4/5 for confidence and knowledge, 3/5 for experience, and
      2/5 for training. The highest scores were for medical, anaesthetics, and
      interpersonal skills. Consultants attributed lack of exposure to underperformance
      more frequently than lack of training. CONCLUSIONS: Trainees and trainers agree
      on the level of exposure to various clinical challenges, but disagree on
      training. Trainees' levels of confidence and knowledge outweigh their experience
      and training, suggesting that trainees associate knowledge with clinical
      competence.

PMID- 16794091
TI  - Risk factors for heat related death during the August 2003 heat wave in Paris,
      France, in patients evaluated at the emergency department of the Hopital Europeen
      Georges Pompidou.
AB  - OBJECTIVES: This study sought to determine the risk factors for short term
      mortality in the victims of the heat wave of August 2003 in France from among
      patients evaluated in our emergency department (ED). It was hypothesised that
      age, temperature, and some long term therapies and pre-existing pathologies were
      factors associated with short term mortality. METHODS: A retrospective analysis
      of a seven day period. Four experts decided blindly, in pairs, whether a patient
      had presented with a heat related problem. Inclusion criteria were: core
      temperature > or =38 degrees C and/or clinical signs of dehydration. Comparisons
      were made between the survivors and one month non-survivors for 57 different
      items. Short term mortality was defined as death in the ED or within the first
      month of the ED visit. RESULTS: Of 841 patients attending the ED in the study
      period, 165 were included in the study, of which most were elderly women. Thirty
      one (18.8%) died within one month. Factors associated with short term mortality
      were: a greater degree of dependent living; more severe clinical condition on
      admission (higher temperature and heart rate, lower blood pressure, hypoxia, and
      altered mental status); higher values of blood glucose, troponin, and white blood
      cell count; lower values of serum protein and prothrombin levels; pre-existing
      ischaemic cardiomyopathy; pneumonia as associated infection; and previous
      psychotropic treatment. The total number of survivors at one year was 91.
      CONCLUSIONS: Although this study is limited because of the small sample size, the
      results have helped determine factors useful for future identification of
      patients at greatest risk of death in order to implement a more efficient patient
      care protocol.

PMID- 16794092
TI  - Severe head injury in children: emergency access to neurosurgery in the United
      Kingdom.
AB  - OBJECTIVE: To determine the scale of acute neurosurgery for severe traumatic
      brain injury (TBI) in childhood, and whether surgical evacuation for haematoma is
      achieved within four hours of presentation to an emergency department. METHODS: A
      12 month audit of emergency access to all specialist neurosurgical and intensive
      care services in the UK. Severe TBI in a child was defined as that necessitating
      admission to intensive care. RESULTS: Of 448 children with severe head injuries,
      91 (20.3%) underwent emergency neurosurgery, and 37% of these surgical patients
      had at least one non-reactive and dilated pupil. An acute subdural or epidural
      haematoma was present in 143/448 (31.9%) children, of whom 66 (46.2%) underwent
      surgery. Children needing surgical evacuation of haematoma were at a median
      distance of 29 km (interquartile range (IQR) 11.8-45.7) from their neurosurgical
      centre. One in four children took longer than one hour to reach hospital after
      injury. Once in an accident and emergency department, 41% took longer than fours
      hours to arrive at the regional centre. The median interval between time of
      accident and arrival at the surgical centre was 4.5 hours (IQR 2.23-7.73), and
      79% of inter-hospital transfers were undertaken by the referring hospital rather
      than the regional centre. In cases where the regional centre undertook the
      transfer, none were completed within four hours of presentation-the median
      interval was 6.3 hours (IQR 5.1-8.12). CONCLUSIONS: The system of care for
      severely head injured children in the UK does not achieve surgical evacuation of
      a significant haematoma within four hours. The recommendation to use specialist
      regional paediatric transfer teams delays rather than expedites the emergency
      service.

PMID- 16794093
TI  - Management of nasal injuries by UK accident and emergency consultants: a
      questionnaire survey.
AB  - OBJECTIVES: To determine how nasal injuries are managed by accident and emergency
      (A&E) consultants and produce a management protocol if the survey indicated a
      need. METHOD: A postal survey of UK A&E consultants. RESULTS: The response rate
      was 59%. A great deal of variation was found between departments and clinicians
      regarding the training of junior A&E staff, the equipment available, the
      management strategies employed, and the reasons for referral to ENT or
      maxillofacial departments. CONCLUSIONS: This survey shows that many more nasal
      injuries could be managed within the A&E setting without referral to ENT or
      maxillofacial departments. A flow chart of the optimal management of nasal
      injuries in Accident and Emergency departments is presented.

PMID- 16794094
TI  - An audit of corneal abrasion management following the introduction of local
      guidelines in an accident and emergency department.
AB  - BACKGROUND AND OBJECTIVES: Corneal abrasions are a common presentation to
      accident and emergency (A&E) departments. Patients can be treated and discharged
      by A&E staff without the need for an ophthalmologist's attention; complicated
      cases, however, should be recognised and referred. Inexperience and limited
      training in ophthalmology may lead to suboptimal patient care and inappropriate
      use of ophthalmology outpatient clinics. Issues of poor documentation may also
      arise. The purpose of this audit was to assess the effect of guidelines on the
      management of corneal abrasion by A&E staff. METHODS: A retrospective case note
      audit was performed to assess current management of corneal abrasions. Guidelines
      for management of corneal abrasions were formulated following a literature search
      and collaboration between A&E and ophthalmology staff. A prospective case note
      audit was undertaken to assess management after introduction of the guidelines.
      RESULTS: A total of 51 cases were audited before the introduction of the
      guidelines and 57 cases after. Following the introduction of the guidelines
      documentation of visual acuity increased to 93% and specific enquiry into contact
      lens wear rose from 35.3% to 71.9%. A&E staff stopped giving out local
      anaesthetic eye drops. The follow up profile also improved; appropriate patient
      discharges increased by 40% whereas inappropriate referrals to eye clinic dropped
      by 75%. More patients were given abrasion advice (a 101% increase). CONCLUSIONS:
      A&E staff members are capable of managing corneal abrasions if they are given
      guidance and some training. This audit identified shortcomings in current
      management and showed that guidelines can significantly improve clinical
      practice.

PMID- 16794095
TI  - The casualty profile from the Reading train crash, November 2004: proposals for
      improved major incident reporting and the application of trauma scoring systems.
AB  - OBJECTIVE: To report the casualty profile of the major incident at the Royal
      Berkshire Hospital, Reading, following the Ufton Nervet Train crash, November
      2004. To make further proposals regarding major incident reporting and
      implementation of trauma-scoring systems. METHOD: Retrospective analysis of
      emergency department and hospital notes. Calculation of index Injury Severity
      Score (ISS) and Trauma and Injury Severity Score (TRISS) in all patients.
      RESULTS: Of 61 casualties, the majority (74%) were seen in the minors area of our
      emergency department with a mixture of blunt impact and penetrating glass
      injuries. One died and 16 were admitted. 10% had an ISS >16. All surviving
      patients had a TRISS predicted probability of survival >90%. CONCLUSION: We
      propose mandatory major incident reporting within 6 months of a major incident to
      aid development of a national database. As previously proposed, this will aid
      education and facilitate future major incident planning. We further propose the
      widespread use of trauma scoring systems to facilitate comparative analysis
      between major incidents, perhaps extrapolating this to develop a major incident
      score.

PMID- 16794096
TI  - EMTs and GPs: what do we think of each other?
AB  - BACKGROUND: Ireland's health services are undergoing dramatic reorganisation. The
      establishment of general practitioner (GP) out of hours cooperatives and the
      integration of current ambulance services into a national ambulance service are
      among the issues that will impact on prehospital care of emergencies. The study
      aimed to explore the perceptions of GPs and emergency medical technicians (EMTs)
      of their own and each other's roles in the context of such reforms. METHODS: A
      census of all GPs (511) and EMTs (301) in three of Ireland's eight health board
      regions was undertaken. A questionnaire containing 31 statements asked
      respondents to indicate their agreement (or lack of it) in areas such as general
      relationships, care, and training, roles in emergencies and future developments.
      RESULTS: Of the personnel contacted, 72% of GPs and 75% of EMTs responded. They
      report excellent working relationships, agree that the ambulance service is of
      high quality, and that GPs are willing to provide care in emergencies. However,
      working links are less satisfactory for EMTs, who report a far higher perception
      of GP use of emergency ambulances than reported by GPs. Both groups are
      interested in innovative future links. DISCUSSION: Convergence between the
      professional groups in different geographic areas and between the disciplines
      across the areas is striking. They include areas of satisfaction and
      dissatisfaction. The need for improved liaison between the disciplines is clear.

PMID- 16794097
TI  - Evaluation of effects of ischaemia on the albumin cobalt binding (ACB) assay in
      patients exposed to trauma.
AB  - BACKGROUND: In the emergency department (ED), the diagnosis of acute myocardial
      ischaemia is very difficult because of the absence of a rapid, reliable
      diagnostic test. The albumin cobalt binding (ACB) assay is a good candidate as a
      marker for for detection of myocardial ischaemia, as it is an easy and rapid
      test. To date, however, the way in which alterations in metal binding sites of
      human serum albumin depend on ischaemic events has not been reported in detail.
      METHODS: We studied 92 patients admitted to the ED within 1 hour after exposure
      to trauma. Trauma patients divided into two groups according to their Injury
      Severity Score (ISS): group 1 comprised mildly injured patients who had ISS
      trauma score <15 (n = 60), and group 2 comprised moderately injured patients with
      ISS trauma score >15 (n = 32). The blood specimens of 30 healthy volunteers were
      studied as a control group. RESULTS: Group 2 showed significantly increased ACB
      levels (0.63 (0.18) absorbance units (ABSU)) compared with group 1 (0.54 (0.14)
      ABSU) (p<0.05) and controls (0.39 (0.05) ABSU) (p<0.01). Group 1 showed
      significantly enhanced ACB values compared with controls (0.54 (0.14) v 0.39
      (0.05) ABSU) (p<0.01). CONCLUSION: Consequently, trauma enhances ACB levels,
      which may affect the diagnostic performance of the ACB assay, and this effect can
      limit the ability of the assay for detection of myocardial ischaemia in patients
      exposed to trauma.

PMID- 16794098
TI  - Childhood falls: characteristics, outcome, and comparison of the Injury Severity
      Score and New Injury Severity Score.
AB  - OBJECTIVES: The aim of this study was to determine the general characteristics of
      childhood falls, factors affecting on mortality, and to compare the Injury
      Severity Score (ISS) and the New Injury Severity Score (NISS) as predictors of
      mortality and length of hospital stay in childhood falls. METHODS: We
      retrospectively analysed over a period of 8 years children aged younger than14
      years who had sustained falls and who were admitted to our emergency department.
      Data on the patients' age, sex, type of fall, height fallen, arrival type, type
      of injuries, scoring systems, and outcome were investigated retrospectively. The
      ISS and NISS were calculated for each patient. Comparisons between ISS and NISS
      for prediction of mortality were made by receiver operating characteristic (ROC)
      curve and Hosmer-Lemeshow (HL) goodness of fit statistics. RESULTS: In total,
      there were 2061 paediatric trauma patients. Falls comprised 36 (n = 749) of these
      admissions. There were 479 male and 270 female patients. The mean (SD) age was
      5.01 (3.48) years, and height fallen was 3.8 (3) metres. Over half (56.6%) of
      patients were referred by other centres. The most common type of fall was from
      balconies (38.5%), and head trauma was the most common injury (50%). The overall
      mortality rate was 3.6%. The cut off value for both the ISS and NISS in
      predicting mortality was 22 (sensitivity 90.5%, specificity 95.4% for ISS;
      sensitivity 100%, specificity 88.7% for NISS) (p>0.05). Significant factors
      affecting mortality in logistic regression analysis were Glasgow Coma Scale (GCS)
      <9, ISS >22, and NISS >22. There were no significant differences in ROC between
      three scoring systems. The HL statistic showed poorer calibration (p = 0.02 v p =
      0.37, respectively) of the NISS compared with the ISS. CONCLUSIONS: In our
      series, the head was the most frequent site of injury, and the most common type
      of fall was from balconies. Scores on the GCS, NISS, and ISS are significantly
      associated with mortality. The performance of the NISS and ISS in predicting
      mortality in childhood falls was similar.

PMID- 16794100
TI  - High dose methylprednisolone in the immediate management of acute, blunt spinal
      cord injury: what is the current practice in emergency departments, spinal units,
      and neurosurgical units in the UK?
AB  - BACKGROUND: The National Acute Spinal Cord Injuries Studies and the Cochrane
      Review advocate the administration of high dose methylprednisolone following
      acute traumatic spinal cord injury. However, controversy surrounds its use and
      approaches between different units are often inconsistent. METHODS: A
      questionnaire was sent to all emergency departments receiving major trauma and
      all specialist neurosurgical and spinal units in the UK to determine the current
      practice regarding the use of high dose methylprednisolone in the immediate
      management of acute, blunt spinal cord injuries. RESULTS: Of 250 emergency
      departments, 187 replied to the questionnaire. Twelve of the 26 departments with
      a neurosurgical or spinal service on site stated they received consistent advice
      from specialist teams. Sixty four departments had a written policy regarding the
      treatment of spinal injuries, which in 51 departments contained advice about the
      administration of methylprednisolone. Of the 128 departments who gave
      methylprednisolone, 88 did so only on the advice of a specialist team, with the
      remaining 40 giving steroids immediately on identification of the injury. Ten out
      of 11 spinal units replied, of whom only two advised the used of steroids. Of the
      34 neurosurgical units approached, seven out of 17 responders had a policy
      recommending the use of steroids. Of the 10 units who did not consistently
      recommend the use of steroids, seven had practise that varied between
      consultants. CONCLUSION: Currently practice varies in the UK regarding the
      immediate use of methylprednisolone after spinal injury. Clear guidelines need to
      be established to achieve a more consistent approach.

PMID- 16794101
TI  - Patient self assessment of pregnancy status in the emergency department.
AB  - OBJECTIVES: Pregnancy tests are often performed routinely for female emergency
      department (ED) patients of reproductive age. One major reason is a perception
      that patients are unreliable in predicting their own pregnancy status. We
      hypothesised that patients could reliably predict that they were not pregnant.
      METHODS: The study used a prospective cohort design, in an urban academic ED,
      from January 19 to May 19, 2004. All patients for whom a pregnancy test was
      ordered were asked about their sexual history as well as two additional
      questions: "Do you think you might be pregnant?" and "Is there any chance you
      could be pregnant?" Patients with already documented pregnancies were excluded.
      RESULTS: A total of 474 patients had pregnancy tests performed that met inclusion
      criteria. Eleven (2.3%) tests were positive. Among patients who answered no to
      both questions (337), one test (0.3%) was positive (negative predictive value
      (NPV) 99.7%, likelihood ratio (LR) 0.13 (95% CI, 0.02 to 0.82)). The other
      historical factor with a high NPV (100%) was not being sexually active (LR not
      calculable). All pregnancies occurred in patients with gastrointestinal or
      genitourinary as the chief complaint: this comprised only 56% of the
      presentations for which tests were ordered. CONCLUSION: Sexual history and self
      assessment can be used as a highly effective predictor of a patient not being
      pregnant. Given the risks of missed pregnancy in the ED, and low monetary and
      time cost of pregnancy tests, frequent testing is still recommended in most
      instances.

PMID- 16794099
TI  - The effects of commonly used resuscitation fluids on whole blood coagulation.
AB  - OBJECTIVES: Evidence on the effect of crystalloid and colloid resuscitation
      fluids on coagulation is confusing, with contradictory results from previous
      studies. This study was performed to test the effect on whole blood coagulation
      of a range of resuscitation fluids in vitro using a single method at a single
      dilution. METHODS: Seven resuscitation fluids were tested in vitro at a dilution
      of 40%. Whole blood coagulation was measured using a Sonoclot analyser. RESULTS:
      A crystalloid/colloid split of effect on coagulation in vitro was not seen. The
      time to clot formation with Gelofusine, dextran and hydroxyethyl starch was a
      greatly increased, whereas saline and Haemaccel had little effect, or were
      slightly procoagulant. CONCLUSIONS: Some resuscitation fluids have a profound
      effect on coagulation. The confusion in the literature may result from the effect
      on coagulation being both fluid and dilution dependent, with no simple
      crystalloid/colloid split.

PMID- 16794102
TI  - Are these emergency department performance data real?
AB  - We have recently demonstrated that the distribution of total time spent by
      patients in emergency departments (EDs) in England shows a peak immediately prior
      to the current Department of Health target of 4 hours. We aimed to investigate
      whether this suggested that performance data were being manipulated. We collected
      data from 117 EDs, and 616,067 patient episodes were included in the analysis.
      Evidence of manipulation of performance data appears to be present in a small
      proportion of episodes, but because of the numbers involved, it could equate to
      over 50,000 episodes per year in EDs in England.

PMID- 16794103
TI  - Critical care in the emergency department: introduction.

PMID- 16794104
TI  - Critical care in the emergency department: monitoring the critically ill patient.
AB  - The aim of monitoring patients is to detect organ dysfunction and guide the
      restoration and maintenance of tissue oxygen delivery. Monitoring is a crucial
      part of the care of the critically ill patient in the emergency department as the
      physiological response to critical illness is linked strongly to outcome. As it
      is important to appreciate the limitations of monitoring systems and monitored
      data, and to understand that invasive monitoring may be hazardous, this review
      concentrates on the techniques used to monitor critically ill patients in the
      emergency department. End tidal carbon dioxide monitoring, pulse oximetry,
      arterial blood pressure monitoring, central venous pressure monitoring,
      continuous central venous oxygenation saturation monitoring, temperature
      monitoring, and urine output are discussed. Practitioners should be familiar with
      the physiology and technology underlying these monitoring techniques and be aware
      of the pitfalls in interpretation of monitored data.

PMID- 16794105
TI  - Toxicology case of the month: oral hypoglycaemic overdose.
AB  - A teenager ingests 375 mg of glipizide and 14.5 g of melformin intentionally in a
      small country town. She presents to the local medical facility with symptoms and
      signs of hypoglycaemia. Using a risk assessment based approach, the management of
      suiphonylurea and metformin overdose is discussed. Sulphonylurea overdose
      invariably results in profound hypoglycaemia that requires resuscitation with IV
      dextrose and the use of octreotide as an antidote. Metfonnin overdose rarely
      causes problems.

PMID- 16794106
TI  - Best evidence topic report. Cocaine induced myocardial ischaemia: nitrates versus
      benzodiazepines.
AB  - A short cut review was carried out to establish whether nitrates are better than
      benzodiazepines in the treatment of cocaine induced chest pain. Seven citations
      were reviewed of which two answered the three part question. The clinical bottom
      line is that in patients with cocaine induced chest pain it appears that nitrates
      or benzodiazepines are effective in combination or alone in resolving chest pain
      and improving cardiac performance. We recommend that the agent of choice may be
      influenced by the presence or absence of concurrent CNS symptoms.

PMID- 16794108
TI  - Best evidence topic report. The use of loop diuretics in acute renal failure in
      critically ill patients to reduce mortality, maintain renal function, or avoid
      the requirements for renal support.
AB  - A short cut review was carried out to establish whether loop diuretics are useful
      for critically ill patients with renal failure. A total of 1017 citations were
      reviewed of which two answered the three part question. The clinical bottom line
      is that in critically ill patients with acute renal failure, there is no evidence
      to suggest that the use of loop diuretics reduces mortality, reduces length of
      ITU/hospital stay, or increases the recovery of renal function.

PMID- 16794110
TI  - Best evidence topic report. Hyperbaric oxygen therapy in acute fracture
      management.
AB  - A short cut review was carried out to establish whether hyperbaric oxygen therapy
      (HBOT) is advantageous in fracture healing. A total of 26 citations were found of
      which one answered the three part question. The clinical bottom line is that
      there is insufficient evidence to support the use of hyperbaric oxygen therapy
      for fracture healing.

PMID- 16794109
TI  - Best evidence topic report. Kocher's or Milch's technique for reduction of
      anterior shoulder dislocations.
AB  - A short cut review was carried out to establish whether Kocher's or Milch's
      technique was better at reducing shoulder dislocations. A total of 304 papers
      were found of which one answered the three part question. The clinical bottom
      line is that the individual preference of physicians for either Kocher's or
      Milch's method of reduction is not supported by the evidence.

PMID- 16794111
TI  - The internationalisation of prehospital education: a merging of ideologies
      between Australia and the USA.
AB  - The aim of this project was to promote internationalisation of prehospital
      education collaboratively between students and teachers from EMS Education and
      Training, Montana, USA, and Monash University Centre for Ambulance and Paramedic
      Studies (MUCAPS), Victoria, Australia. The project required students and teachers
      to engage in a series of face to face lectures, which was reinforced through
      distance education strategies, such as online learning. The overall project aim
      was to establish an objective and descriptive view of the internationalisation of
      prehospital and community based emergency health education using e-learning as
      the educational approach. A cross sectional survey design using paper based
      evaluation was adopted in this project. Results revealed a positive student
      reaction, with flexible pedagogical processes broadening student learning and
      facilitating an international dimension otherwise not achievable. Given the
      current state of globalisation, internationalisation has the capacity to improve
      educational standards, quality, student interactions and specific learning
      outcomes in prehospital education.

PMID- 16794112
TI  - EtCO2: the key to effective prehospital ventilation.

PMID- 16794113
TI  - Case of the month: Right coronary artery dissection following sports-related
      blunt trauma.
AB  - Coronary artery dissection is a rare life-threatening complication resulting from
      blunt traumatic injury. Most cases of coronary artery injury, including
      dissection, involve the left anterior descending artery given its anatomical
      location relative to the impact. Right coronary artery (RCA) dissection secondary
      to blunt trauma is a particularly unusual occurrence, and has not previously been
      reported in the emergency medicine literature. We present a case of RCA
      dissection following low impact sport-related blunt chest trauma and discuss the
      pathophysiology, risk factors, diagnosis and current treatment options.

PMID- 16794114
TI  - The missed clavicle fracture in children?

PMID- 16794115
TI  - Spontaneous sublingual haematoma resulting in airway obstruction.

PMID- 16794117
TI  - Green fingers, red eyes! Ocular hazards of gardening.

PMID- 16794116
TI  - Use of intravenous cyclizine in cardiac chest pain.

PMID- 16794118
TI  - New recommendation for N-acetylcystiene dosing may reduce incidence of adverse
      effects.

PMID- 16794119
TI  - Use of a screwdriver in the emergency department.

PMID- 16794120
TI  - Pacing in hypothermia: does it work?

PMID- 16794121
TI  - Variability of repeated coronary artery calcium measurements on low-dose ECG
      gated 16-MDCT.
AB  - OBJECTIVE: High reproducibility on coronary artery calcium (CAC) scoring is a key
      requirement in monitoring the progression of coronary atherosclerosis.
      Retrospective ECG-gated helical CT has been shown to be superior to prospective
      gating helical CT in the reproducibility of CAC measurements. However, it brings
      with it a high level of radiation exposure. The purpose of this study was to
      compare low- and standard-dose protocols in the variability of CAC scores and in
      image quality, thereby assessing the feasibility of low-dose retrospective ECG
      gated helical CT in CAC measurements. SUBJECTS AND METHODS: Eighty-six patients
      with CAC were scanned using a tube current setting of 100 mA once and then a tube
      current setting equivalent to the patient's body weight twice. CAC scores
      (Agatston and volume) and interscan variability were evaluated. The mean and SD
      of the CT attenuation values in regions of interest in the aorta were measured,
      and the value (mean + 2 x SD) was obtained. RESULTS: A high correlation of
      log(10) (Agatston score + 1) was observed between sequential helical CT scans (r
      = 0.998). The variability in CAC measurements ranged from 11% to 12% for both the
      Agatston and volume scores. With the tube current equivalent to body weight, the
      value (mean + 2 x SD) did not exceed a CT attenuation value of 130 H. CONCLUSION:
      Low-dose retrospective ECG-gated helical CT-yielding low variability and
      achieving the level of image quality needed to measure CAC-can be used to monitor
      patients with coronary atherosclerosis.

PMID- 16794122
TI  - Opposed-phase MRI for fat quantification in fat-water phantoms with 1H MR
      spectroscopy to resolve ambiguity of fat or water dominance.
AB  - OBJECTIVE: The purpose of the study was to quantify the fat fraction in nine fat
      water phantoms containing 0-80% fat using opposed-phase imaging with the
      qualitative guidance of 1H MR spectroscopy (MRS), which was used by observer 1 to
      visually assess the sizes of the water and fat peaks to apply two alternative
      mathematic formulas for the calculation of the fat fraction. In addition, the fat
      fraction was also quantified directly with 1H MRS as an independent method by two
      observers (observers 2 and 3). CONCLUSION: The fat fraction calculated with
      opposed-phase imaging (FF(OPI)) and that calculated with 1H MRS (FF(MRS))
      correlated well with the known fat fractions of the phantoms (FF(P)): r = 0.99
      for FF(OPI); p < 0.0001 and r = 0.96-0.98 for FF(MRS); p < 0.001, for observers 2
      and 3, respectively. Opposed-phase imaging should be combined with 1H MRS to
      ensure accurate quantification of the fat fraction.

PMID- 16794123
TI  - 2D cine phase-contrast MRI for volume flow evaluation of the brain-supplying
      circulation in moyamoya disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate and quantify hemodynamic
      compromise in patients with moyamoya disease by measuring blood volume flow in
      the brain-supplying arteries. SUBJECTS AND METHODS: Thirty-five patients with
      angiographically proven moyamoya disease (31 women, 4 men; mean age, 39.4 +/-
      12.2 years; range, 15-58 years; adult moyamoya disease) and 15 age-matched
      healthy controls were examined prospectively with 2D cine phase-contrast MRI.
      Blood volume flow was measured in both common carotid arteries (CCAs), both
      internal carotid arteries (ICAs), and the basilar artery. The diagnosis of
      moyamoya disease was based on results of selective intraarterial digital
      subtraction angiography. RESULTS: Blood volume flow of the brain-supplying
      arteries in age-matched controls was 435.6 +/- 47.9 mL/min for the CCA, 254.1 +/-
      25.3 mL/min for the ICA, and 173.3 +/- 13.2 mL/min for the basilar artery.
      Patients with bilateral moyamoya disease had decreased mean blood flow in the CCA
      (309.4 +/- 89.9 mL/min) and ICA (117.9 +/- 64.0 mL/min) and increased blood
      volume flow in the basilar artery (433.7 +/- 165.9 mL/min). CONCLUSION: Moyamoya
      disease causes a significant decrease in carotid artery circulation, particularly
      ICA blood volume flow, with a compensatory increase in blood flow in the basilar
      artery to nearly 2.5 times normal basilar artery blood flow. 2D cine phase
      contrast MRI with measurement of blood volume flow in the brain-supplying
      arteries is useful in the initial evaluation of moyamoya disease and in
      continuing assessment of hemodynamics in patients with this disease.

PMID- 16794125
TI  - Additional descriptions of true gastric intussusception.

PMID- 16794124
TI  - Acne vulgaris: false-positive finding on integrated 18F-FDG PET/CT in a patient
      with melanoma.

PMID- 16794126
TI  - Intraoperative sonographically guided needle localization of nonpalpable
      testicular tumors.

PMID- 16794127
TI  - Portal vein embolization: a plea for strict patient selection.

PMID- 16794128
TI  - Sonographic features of abdominal wall endometrioma.

PMID- 16794129
TI  - MDCT angiography in patients with traumatic extremity injuries.

PMID- 16794130
TI  - On the AJR digital viewbox. Imaging of Kimura' s disease involving the abdomen.

PMID- 16794131
TI  - On the AJR digital viewbox. Bilateral pulmonary sequestration with bridging
      isthmus in a boy with Williams syndrome.

PMID- 16794132
TI  - On the AJR digital viewbox. Lymph node-like lesion of the neck after
      pharyngolaryngectomy.

PMID- 16794133
TI  - On the AJR digital viewbox. Large synovial cyst arising from the sacroiliac
      joint.

PMID- 16794135
TI  - Adrenocortical carcinoma: contrast washout characteristics on CT.
AB  - OBJECTIVE: The purpose of this study was to characterize pathologically proven
      adrenocortical carcinoma by examination of washout attenuation characteristics on
      contrast-enhanced CT images. CONCLUSION: Adrenocortical carcinoma has relative
      contrast retention on delayed contrast-enhanced CT. All tumors in this series had
      a relative percentage washout less than 40%, a finding consistent with malignant
      disease.

PMID- 16794134
TI  - Inferior phrenic arterial bleeding after adult liver transplantation: incidence,
      clinical manifestations, and predictive CT features.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of inferior
      phrenic arterial bleeding after liver transplantation in adult patients and to
      describe its clinical manifestations and predictive CT features. CONCLUSION:
      Inferior phrenic arterial bleeding occurs frequently and is one of the major
      postoperative bleeding sites in patients undergoing liver transplantation.
      Awareness of its common clinical manifestations and predictive CT features is
      essential for prompt diagnosis and treatment of this early vascular complication,
      and this knowledge can help to avoid unnecessary reoperation and catastrophic
      hypotension.

PMID- 16794137
TI  - Sonography of Budd-Chiari syndrome.
AB  - OBJECTIVE: The purpose of this pictorial essay is to review the color Doppler
      sonographic features of Budd-Chari syndrome. CONCLUSION: Combining color and
      spectral data, sonography provides hemodynamic and anatomic information about
      vessel patency and collateral vessel formation. The diagnosis of Budd-Chari
      syndrome is based on the involvement of hepatic veins although intrahepatic
      collateral circulation and dilated caudate veins are also important and frequent
      signs. Half of the patients will develop regenerative nodules that can simulate
      hepatocellular carcinoma.

PMID- 16794136
TI  - MDCT of the liver and hypervascular hepatocellular carcinomas: optimizing scan
      delays for bolus-tracking techniques of hepatic arterial and portal venous
      phases.
AB  - OBJECTIVE: The purpose of our study was to determine the optimal scan delays
      required for hepatic arterial and portal venous phase imaging and for the
      detection of hypervascular hepatocellular carcinomas (HCCs) in contrast-enhanced
      MDCT of the liver using a bolus-tracking program. SUBJECTS AND METHODS: CT images
      (2.5-mm collimation, 5-mm thickness with no intersectional gap) detected an
      increase in the CT value of 50 H in the lower thoracic aorta. The images were
      obtained after an IV bolus injection of 2 mL/kg of nonionic iodine contrast
      material (300 mg I/mL) at 4 mL/s in 171 patients, who were prospectively
      randomized into three groups with scans commencing at 5, 20, and 45 seconds; 10,
      25, and 50 seconds; and 15, 30, and 55 seconds for the first (acquisition time:
      4.3 seconds), second (4.3 seconds), and third (9.1 seconds) phases, respectively,
      after a bolus-tracking program. CT values of the aorta, spleen, proximal portal
      veins, liver parenchyma, and hepatic veins were measured. Increases in CT values
      from unenhanced to contrast-enhanced CT were assessed using a contrast
      enhancement index (CEI). Spleen-to-liver and HCC-to-liver contrasts were also
      assessed. A qualitative degree of contrast enhancement in each organ was
      prospectively assessed by two independent radiologists. RESULTS: At 10-15
      seconds, the CEI of the aorta reached 300-336 H and that of the spleen reached 97
      108 H without significant enhancement of liver parenchyma (15-25 H). The CEI of
      the proximal portal veins moderately increased (75-104 H) at 10-15 seconds, but
      no significant enhancement of hepatic veins was observed (24-51 H). The CEI of
      liver parenchyma peaked (59-63 H) at 45-55 seconds, when the CEIs of the aorta
      (117-125 H) and spleen (73-82 H) decreased. Spleen-to-liver contrast (81-84 H)
      was highest at 10-20 seconds and HCC-to-liver contrast (39-44 H) was highest at
      10-15 seconds. The qualitative results correlated well with quantitative results.
      CONCLUSION: The optimal scan delays for hepatic arterial and portal venous phases
      after the bolus-tracking program detected threshold enhancement by 50 H in the
      lower thoracic aorta for the detection of hypervascular HCCs were 10-15 and 45-55
      seconds, respectively.

PMID- 16794138
TI  - Peliosis hepatis: spectrum of imaging findings.
AB  - OBJECTIVE: It is important to recognize the imaging characteristics of peliosis
      hepatis because peliotic lesions may mimic several different types of focal
      hepatic lesions CONCLUSION: We illustrate the spectrum of imaging findings of
      peliosis hepatis, including sonography, CT, MR, and angiography.

PMID- 16794139
TI  - Posterior ankle impingement in professional soccer players: effectiveness of
      sonographically guided therapy.
AB  - OBJECTIVE: The objective of our study was to describe the use of MRI and evaluate
      the efficacy of sonographically guided injection of steroid and anesthetic in the
      management of posterior ankle impingement in elite athletes. CONCLUSION: The
      results show a role for sonographically guided steroid and anesthetic injection
      into a posterolateral capsule abnormality in athletes with clinical posterior
      impingement. The procedure was well tolerated and allowed a rapid return to
      athletic activity in all patients.

PMID- 16794140
TI  - Numbering of lumbosacral transitional vertebrae on MRI: role of the iliolumbar
      ligaments.
AB  - OBJECTIVE: The objective of this study was to determine whether identification of
      the iliolumbar ligaments is of practical use for numbering lumbosacral
      transitional vertebrae (LSTV). MATERIALS AND METHODS: Five hundred consecutive
      lumbar spine MRI studies were reviewed. A standard protocol of sagittal and axial
      T1-weighted and T2-weighted spin-echo sequences was used. The sagittal images
      were assessed for the presence of an LSTV, and axial images were assessed for the
      level of origin of the iliolumbar ligaments. RESULTS: Of the 500 patients, 433
      (86.6%) had normal lumbosacral segmentation and 67 (13.4%) had a transitional
      lumbosacral junction. The iliolumbar ligament was identified at L5 in all
      patients with normal lumbosacral segmentation (n = 433), bilaterally in 432 and
      unilaterally in one. Using the identification of the iliolumbar ligaments as a
      marker of the L5 vertebral level, we numbered 46 of the 67 LSTV as L5 transitions
      and 21 as S1 transitions. CONCLUSION: The iliolumbar ligament is readily
      identifiable on axial lumbar spine MRI and always arises from L5. We suggest that
      its position can be used to confidently assign lumbar levels in patients with
      LSTV.

PMID- 16794141
TI  - Calcific myonecrosis: keys to recognition and management.
AB  - OBJECTIVE: Calcific myonecrosis masses can become quite large and worrisome for
      malignancy. The key to recognition is a combination of radiologic imaging
      features and remote clinical history of injury associated with compartment
      syndrome or vascular or neurologic compromise. CONCLUSION: This article will
      highlight importance of correct diagnosis by identifying the severe and
      devastating complications following inappropriate management.

PMID- 16794142
TI  - Acute pulmonary embolism to the subsegmental level: diagnostic accuracy of three
      MRI techniques compared with 16-MDCT.
AB  - OBJECTIVE: The purpose of this study was to assess the individual and combined
      usefulness of MRI techniques in cases of acute pulmonary embolism and to compare
      the usefulness of these techniques with that of 16-MDCT. SUBJECTS AND METHODS:
      Sixty-two patients with symptoms indicating acute pulmonary embolism underwent an
      MRI protocol that progressed from real-time MRI through MR perfusion imaging to
      MR angiography. The results were compared with those of 16-MDCT, which was the
      reference standard. Thoracic incidental diagnoses other than pulmonary embolism
      also were sought with CT and MRI. RESULTS: Pulmonary embolism was diagnosed with
      CT in 19 patients for totals of 90 lobar, 245 segmental, and 434 subsegmental
      arteries. On a per-patient basis, the sensitivities of real-time MRI, MR
      angiography, MR perfusion imaging, and the combined protocol were 85%, 77%, 100%,
      and 100%, respectively. The specificities were 98%, 100%, 91%, and 93%. The kappa
      values in a comparison of the MR techniques with CT were 0.89, 0.87, 0.86, and
      0.9. On a per-embolus basis, the sensitivities of real-time MRI, MR angiography,
      and MR perfusion imaging for lobar pulmonary embolism were 79%, 62%, and 100%.
      The sensitivities for segmental pulmonary embolism were 86%, 83%, and 97%,
      respectively. MR perfusion imaging had a sensitivity of 93% for subsegmental
      pulmonary embolism. Eight of nine incidental findings revealed on CT were also
      subsequently diagnosed with real-time MRI. MRI failed to reveal a case of
      emphysema. Mean MRI examination time was 9 minutes 56 seconds. CONCLUSION: The
      combined MR protocol is both reliable and sensitive in comparison with 16-MDCT in
      the diagnosis of pulmonary embolism. MR perfusion imaging is sensitive for the
      detection of pulmonary embolism, whereas real-time MR and MR angiography are
      specific.

PMID- 16794144
TI  - Transhepatic puncture of portal and hepatic veins for TIPS using a single-needle
      pass under sonographic guidance.
AB  - OBJECTIVE: Creating transjugular intrahepatic portosystemic shunts (TIPS)
      requires accessing a portal vein branch from a metal cannula wedged in a hepatic
      vein. This initial step in shunt creation often requires multiple blind
      intrahepatic punctures and occasionally fails. We describe a method using
      sonographic guidance to serially puncture the portal vein and hepatic vein with a
      single transhepatic needle pass, after which the TIPS procedure is completed in
      the standard transjugular fashion. CONCLUSION: Sonographically guided
      transhepatic dual puncture of the portal and hepatic veins facilitates
      portosystemic shunt creation in a single needle pass and allows more controlled
      selection of the portal vein entry and hepatic vein landing sites in selected
      patients.

PMID- 16794143
TI  - High-spatial-resolution contrast-enhanced MR angiography of abdominal arteries
      with parallel acquisition at 3.0 T: initial experience in 32 patients.
AB  - OBJECTIVE: The objective of our study was to evaluate an isotropic high-spatial
      resolution 3D contrast-enhanced MR angiography (CE-MRA) protocol with high
      acceleration parallel acquisition at 3.0 T for the display of the abdominal
      vasculature. SUBJECTS AND METHODS: Thirty-two consecutive patients (13 men, 19
      women; age range, 28-88 years) with suspected abdominal arterial disease
      underwent abdominal 3D CE-MRA on a 3.0-T MR system, using a high-spatial
      resolution (0.7 x 0.82 x 0.8 mm3) 3D gradient-refocused echo (GRE) sequence,
      integrated with a generalized autocalibrating partially parallel acquisitions
      (GRAPPA) technique with an acceleration factor of 3. Two vascular radiologists
      evaluated image quality and the presence and degree of arterial stenoses.
      Interobserver variability was calculated, using the kappa coefficient. The
      sensitivity and specificity of the technique were calculated and comparative
      analysis was performed with those of conventional catheter angiography (in eight
      patients) as the standard of reference. RESULTS: The abdominal arterial
      vasculature was visualized with diagnostic image quality in all subjects.
      Arterial stenoses were detected in 148 and 142 arterial segments by observer 1
      and observer 2, respectively, with good interobserver agreement (kappa = 0.75;
      95% confidence interval [CI]: 0.69-0.81). The sensitivity and specificity values
      for CE-MRA for the detection of significant (> 50%) arterial stenoses were 100%
      and 96% for observer 1 and 100% and 92% for observer 2, respectively. There was a
      significant correlation between CE-MRA and conventional angiography (R = 0.96 and
      0.93 for observers 1 and 2, respectively) for the assessment of the degree of
      stenosis. CONCLUSION: The outlined MR angiography protocol at 3.0 T combined with
      parallel acquisition technique renders highly reliable and isotropic high-spatial
      resolution imaging of the abdominal vasculature.

PMID- 16794145
TI  - Preparation of digital movie clips for online journal publication.
AB  - OBJECTIVE: This article presents general guidelines for preparing movie clips for
      online journal publication. CONCLUSION: As more and more radiology journals
      establish an online presence, radiologists wishing to submit journal articles
      with movie clips need to understand the electronic submission process. Viewing a
      movie clip via an online journal is different from viewing one with PowerPoint
      using a local desktop computer because the movie file must first be downloaded
      onto the client computer before it can be displayed. Users thus should be
      cautious in selecting movie format and compression when creating movie clips for
      online journals. This article provides step-by-step demonstrations and general
      guidelines for movie format and compression selections.

PMID- 16794147
TI  - The perils of isolation.

PMID- 16794146
TI  - Imaging utilization in the era of the hospitalist.
AB  - OBJECTIVE: We sought to determine whether hospitalists specifically reduce
      inpatient radiologic testing and radiology costs, which to our knowledge has not
      previously been studied. We examined the number of radiologic studies ordered,
      total cost of radiology utilization, cost per patient, mean length of stay, and
      readmission rates for hospitalists and nonhospitalists across the top-10
      discharge diagnosis related groups for hospitalists from October 2000 to
      September 2001. CONCLUSION: We found no decreases in the utilization of radiology
      resources by hospitalists. Given the increasing volume and importance of
      radiology in clinical decision making, there will be increased pressure to
      justify the costs of these studies. We believe that more data should be collected
      about the use of radiology resources.

PMID- 16794148
TI  - Will Saying "I'm Sorry" Prevent a Malpractice Lawsuit?

PMID- 16794149
TI  - "MRI and CT evaluation of primary bone and soft-tissue tumors"--invited
      commentary.

PMID- 16794150
TI  - Improved cancer detection using computer-aided detection with diagnostic and
      screening mammography: prospective study of 104 cancers.
AB  - OBJECTIVE: This study prospectively evaluated a computer-aided detection (CAD)
      device used with diagnostic and screening mammography by assessing cancers
      detected; tumor sizes, histology, and stage; positive predictive value (PPV) of
      biopsy recommendation; and recall rates before and after CAD introduction.
      SUBJECTS AND METHODS: Interpretations of 9,520 consecutive mammograms were
      recorded without and then with CAD for a 28-month period. Cancer detections based
      on initial radiologist review and additional detections based on CAD findings
      were noted. Recall rates, tumor size and histology, and PPV of biopsy
      recommendation before and after the introduction of CAD were compared. RESULTS:
      Cancers detected only with CAD assistance were 9.6% of all cancers (10 of 104);
      screening-detected cancers increased 13.3% with CAD assistance (four in addition
      to 30 screening-detected cancers). The 95% one-sided confidence boundary using
      binomial distribution is consistent with at least 5.3% for all cancers and 5.1%
      for nonpalpable cancers. The greatest impact was on ductal carcinoma in situ, for
      which CAD increased cancer detection by 14.2% (three added to 21). Similar
      percentages of cancers were detected only with CAD assistance in both screening
      (11.4%; 4 of 35) and diagnostic (9.5%; six of 63) studies. Additional cancers
      were detected using CAD in patients with implants and previous lumpectomy. The
      additional cancers detected with CAD were smaller (p = 0.01 for all cancers, p =
      0.03 for nonpalpable invasive cancer). The screening recall rate increased from
      6.2% to 7.8% after CAD, with a decrease in the biopsy rate and a nonsignificant
      increase in the biopsy PPV from 21.9% to 26.3%. CONCLUSION: CAD resulted in
      detection of more cancers in screening and diagnostic patients, with an increased
      recall rate but no deterioration in PPV of biopsy. Additional cancers detected
      were significantly smaller.

PMID- 16794151
TI  - Association of stellate mammographic pattern with survival in small invasive
      breast tumors.
AB  - OBJECTIVE: We tested whether the stellate mammographic pattern of presentation of
      small breast tumors is a better indicator of survival than other patterns.
      MATERIALS AND METHODS: Patients with primary invasive breast cancer diagnosed in
      1993-1997 were grouped according to the size of the lesion: 0.1-0.9 cm and 1.0
      1.4 cm. Each tumor was placed in one of five mammographic prognostic categories:
      stellate without calcifications; circular without calcifications; and
      calcifications with or without tumor mass in a casting, crushed-stone, or other
      (powdery, punctuate, or round) pattern. To assess reproducibility, a second
      radiologist gave an independent interpretation in the first 109 cases.
      Descriptive data were stratified by tumor size, and tests of association were
      done with an extension of Fisher's exact test. Odds ratios and confidence
      intervals were computed. Weighted log-rank test and Kaplan-Meier survival curves
      were used to compare breast cancer survival in the stellate group compared with
      the other groups. RESULTS: Two hundred one consecutive patients with a median
      follow-up period of 7.4 years were identified. There were nine breast cancer
      deaths. The stellate morphologic pattern was most common (91 [45.3%] of 201
      cases), yet there was only one breast cancer death in this group (survival rate,
      98.9%; 95% confidence interval [CI], 96.7-100%). In the group of stellate lesions
      smaller than 1.0 cm, 67.6% (25/37) of the tumors were well-differentiated without
      lymph node metastasis (30 [96.8%] of 31 cases), and there were no deaths. In the
      group of stellate lesions measuring 1.0-1.4 cm, 66.7% (36/54) of the tumors were
      well-differentiated with a 19.6% risk of lymph node metastasis, one death, and a
      survival rate of 98.1% (52/53; 95% CI, 94.4-100%). Circular tumors accounted for
      29.9% (60/201) of tumors and 55.6% (5/9) of breast cancer deaths. Casting and
      crushed-stone microcalcifications were associated with 33.3% (3/9) of disease
      specific deaths. A weighted kappa value of 0.89 (CI, 0.83-0.94) indicated very
      high agreement of pattern assignment. CONCLUSION: Stellate tumors had a
      significantly better survival prognosis than tumors with other patterns even
      though there were no differences in treatment. By recognizing these small
      malignant lesions, trained radiologists may be able to identify tumors that pose
      negligible risk of breast cancer death.

PMID- 16794152
TI  - Digital and screen-film mammography: comparison of image acquisition and
      interpretation times.
AB  - OBJECTIVE: The objective of our study was to compare acquisition times and
      interpretation times of screening examinations using screen-film mammography and
      soft-copy digital mammography. MATERIALS AND METHODS: Technologist study
      acquisition time from examination initiation to release of the screenee was
      measured for both screen-film and digital mammography (100 cases each) in routine
      clinical practice. The total interpretation time for screening mammography was
      also measured for 183 hard-copy screen-film cases and 181 soft-copy digital cases
      interpreted by a total of seven breast imaging radiologists, four experienced
      breast imagers, and three breast imaging fellows. RESULTS: Screening mammography
      acquisition time averaged 21.6 minutes for screen-film and 14.1 minutes for
      digital, a highly significant 35% shorter time for digital than screen-film (p <
      10(-17)). The average number of images per case acquired with digital mammography
      was higher than that for screen-film mammography (4.23 for screen-film, 4.50 for
      digital; p = 0.047). The total interpretation time averaged 1.4 minutes for
      screen-film mammography and 2.3 minutes for digital mammography, a highly
      significant 57% longer interpretation time for digital (p < 10(-11)). In
      addition, technical problems delaying interpretation were encountered in none of
      the 183 screen-film cases but occurred in nine (5%) of the 181 digital cases.
      CONCLUSION: Compared with screen-film mammography, the use of digital mammography
      for screening examinations significantly shortened acquisition time but
      significantly increased interpretation time. In addition, more technical problems
      were encountered that delayed the interpretation of digital cases.

PMID- 16794154
TI  - Comparison of calcification specificity in digital mammography using soft-copy
      display versus screen-film mammography.
AB  - OBJECTIVE: The purpose of this study was to compare specificity in the
      interpretation of calcifications in soft-copy reviewing of digital mammograms
      versus hard-copy reviewing of screen-film mammograms. MATERIALS AND METHODS: A
      total of 130 consecutive cases with calcifications (44 malignant and 86 benign)
      that had been evaluated with needle or surgical biopsy were collected. Both
      screen-film mammography and soft-copy digital mammography were obtained in the
      same patients under existing research protocols using Fischer Imaging's SenoScan
      (n = 71), Lorad's digital mammography system (n = 35), and GE Healthcare's
      Senographe 2000D (n = 24). Eight trained radiologists scored all lesions--cropped
      or masked to display just the region of interest--both on screen-film and soft
      copy digital mammography with a month between reviews to reduce the effects of
      learning and memory. A 5-point malignancy scale was used, with 1 as definitely
      not, 2 as probably not, 3 as possibly, 4 as probably, and 5 as definitely.
      Reviewers were randomly assigned condition order, and images within each
      condition were randomly ordered. Repeated measures analysis of variance was used
      to test for differences between conditions in specificity computed via
      nonparametric receiver operating characteristic (ROC) study separately for each
      reviewer and condition. RESULTS: Across all reviewers, the mean specificity for 1
      or 2 versus 3, 4, or 5 was 0.803 for screen-film mammography (range, 0.413-0.938;
      SD +/- 0.166) and 0.833 for soft-copy image (range, 0.375-0.951; SD +/- 0.187).
      Although not statistically significant (Student's t test p values from 0.19 to
      0.99 across all cut points), numeric values of specificity were consistently
      higher for soft-copy versus screen-film mammography. No statistical significance
      in specificity was seen using all possible cut points in the 5-point scale,
      although the primary analysis used the cutpoint for differentiation between
      benign and malignant cases as 1 or 2 versus 3, 4, or 5. CONCLUSION: No
      statistically significant difference was shown in specificity achievable using
      soft-copy digital versus screen-film mammography in this study.

PMID- 16794153
TI  - Reality check: perceived versus actual performance of community mammographers.
AB  - OBJECTIVE: Federal regulations mandate that radiologists receive regular albeit
      limited feedback regarding their interpretive accuracy in mammography. We sought
      to determine whether radiologists who regularly receive more extensive feedback
      can report their actual performance in screening mammography accurately. SUBJECTS
      AND METHODS: Radiologists (n = 105) who routinely interpret screening mammograms
      in three states (Washington, Colorado, and New Hampshire) completed a mailed
      survey in 2001. Radiologists were asked to estimate how frequently they
      recommended additional diagnostic testing after screening mammography and the
      positive predictive value of their recommendations for biopsy (PPV2). We then
      used outcomes from 336,128 screening mammography examinations interpreted by the
      radiologists from 1998 to 2001 to ascertain their true rates of recommendations
      for diagnostic testing and PPV2. RESULTS: Radiologists' self-reported rate of
      recommending immediate additional imaging (11.1%) exceeded their actual rate
      (9.1%) (mean difference, 1.9%; 95% confidence interval [CI], 0.9-3.0%). The mean
      self-reported rate of recommending short-interval follow-up was 6.2%; the true
      rate was 1.8% (mean difference, 4.3%; 95% CI, 3.6-5.1%). Similarly, the mean self
      reported and true rates of recommending immediate biopsy or surgical evaluation
      were 3.2% and 0.6%, respectively (mean difference, 2.6%; 95% CI, 1.8-3.4%).
      Conversely, radiologists' mean self-reported PPV2 (18.3%) was significantly less
      than their mean true PPV2 (27.6%) (mean difference, -9.3%; 95% CI, -12.4% to 
      6.2%). CONCLUSION: Despite regular performance feedback, community radiologists
      may overestimate their true rates of recommending further evaluation after
      screening mammography and underestimate their true positive predictive value.

PMID- 16794155
TI  - A new automated software system to evaluate breast MR examinations: improved
      specificity without decreased sensitivity.
AB  - OBJECTIVE: We sought to compare the accuracy of breast MRI interpretations with
      and without a new software application (CADstream) that provides automated
      evaluations of breast MR examinations. MATERIALS AND METHODS: Thirty-three
      consecutive lesions seen only on MRI (nine malignant, 24 benign) were evaluated
      with and without the automated software system. Automated analyses of kinetic
      enhancement for each lesion were recorded at 50%, 80%, and 100% enhancement
      thresholds. Computer-assisted analyses included presence or absence of
      "significant" enhancement and classification of enhancement patterns into percent
      volumes of washout, plateau, and persistent enhancement. Fisher's exact tests
      were performed to compare the likelihood of malignancy based on the presence of
      software-defined significant enhancement at the three thresholds. Enhancement
      profiles of malignant versus benign lesions were compared using the Student's t
      test. RESULTS: All malignant lesions showed significant enhancement at all
      thresholds. Compared with the unassisted interpretations, the computer-assisted
      analyses yielded false-positive rates that were reduced by 25% at a 50% threshold
      (not significant [NS]), 33% at an 80% threshold (p = 0.05), and 50% at a 100%
      threshold for enhancement (p < 0.01). There were no significant differences
      between enhancement profiles of benign and malignant lesions, with all lesions
      showing a wide range of washout, plateau, and persistent patterns of enhancement.
      CONCLUSION: New automated software applied to interpret breast MR examinations
      accurately showed significant enhancement in all the malignant lesions while
      depicting 12 of 24 benign lesions as showing insignificant enhancement. If these
      results are validated by a larger study, the number of unnecessary biopsies of MR
      lesions could be reduced without a concomitant decrease in cancer detection.

PMID- 16794156
TI  - Imaging findings after breast brachytherapy.
AB  - OBJECTIVE: The purpose of this study was to determine whether there are imaging
      changes specific to partial breast radiation therapy with interstitial catheters
      or a single balloon. MATERIALS AND METHODS: The records of 43 of 83 patients
      treated with partial breast irradiation at our institution from June 1996 to
      October 2003 were retrospectively reviewed. The images of 27 patients who had
      received radiation by interstitial catheters and 16 who had received radiation by
      a single balloon were reviewed. Patients were examined for the presence of skin
      thickening, diffuse and focal increased density, mass, lucency, and
      calcifications. Fifteen initial sonograms were ordered to evaluate pain or focal
      findings on mammograms. In addition, two patients underwent one and one patient
      underwent three follow-up sonographic examinations. RESULTS: Mild to moderate
      skin thickening was present in 26 (60%) and no skin thickening in 17 (40%) of the
      43 patients. Forty-one (95%) of the 43 patients had focal increased density.
      Diffuse increased density was seen in only one (2%) of the patients. There was no
      change in overall density in 2 (5%) of the patients. Fifteen (35%) of the 43
      patients had mass or seroma at the first follow-up examination. Central lucency
      was present in 35 (81%) of 43 patients on at least one follow-up study.
      Calcification was present in 8 (19%) of 43 cases. CONCLUSION: Imaging findings
      after breast brachytherapy include the spectrum of findings seen with external
      beam radiation but are more focal. The focal findings may be alarming both
      clinically and radiographically, but biopsy can be avoided in most instances if
      information from the history is correlated with findings from continued follow-up
      of the patient's case.

PMID- 16794157
TI  - Serial therapy-induced changes in tumor shape in cervical cancer and their impact
      on assessing tumor volume and treatment response.
AB  - OBJECTIVE: The purpose of this study was to evaluate the patterns and
      distribution of tumor shape and its temporal change during radiation therapy (RT)
      in cervical cancer and the effect of tumor configuration changes on the
      correlation between region of interest (ROI)-based and diameter-based MRI tumor
      measurement. MATERIALS AND METHODS: Serial MRI examinations (T1-weighted and T2
      weighted images) were performed in 60 patients (age range, 29-75 years; mean,
      53.3 years) with advanced cervical cancer (stages IB2-IVB/recurrent) who were
      treated with RT at four time points: start of RT, during RT (at 2-2.5 and at 4-5
      weeks of RT), and post-RT. Tumor configuration was classified qualitatively into
      oval, lobulated, and complex based on MR film review. Two methods of tumor volume
      measurement were compared: ellipsoid computation of three orthogonal diameters
      (diameter based) and ROI volumetry by delineating the entire tumor volume on the
      MR workstation (ROI based). Temporal changes of tumor shape and the respective
      tumor volumes measured by the two methods were analyzed using linear regression
      analysis. RESULTS: Most tumors (70%) had a non-oval (lobulated and complex) shape
      before RT and became increasingly irregular during and after RT: 84% at 2-2.5
      weeks of RT (p = 0.037), 86% (p = 0.025) at 4-5 weeks, and 96% post-RT (p =
      0.010), compared with 70% pre-RT. Diameter-based and ROI-based measurement
      correlated well before RT (r = 0.89) but not during RT (r = 0.68 at 2-2.5 weeks,
      r = 0.67 at 4-5 weeks of RT). CONCLUSION: Most cervical cancers are not oval in
      shape pretherapy, and they become increasingly irregular during and after therapy
      because of nonconcentric tumor shrinkage. ROI-based volumetry, which can
      optimally measure irregular volumes, may provide better response assessment
      during treatment than diameter-based measurement.

PMID- 16794158
TI  - How predictive is breast arterial calcification of cardiovascular disease and
      risk factors when found at screening mammography?
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      breast arterial calcification (BAC), commonly found on mammography, and
      cardiovascular disease and its risk factors. SUBJECTS AND METHODS: The study
      population, nested within the European Prospective Investigation of Cancer
      Norfolk (EPIC-Norfolk) cohort study, consisted of 1,590 women older than 55
      years, not taking hormone replacement therapy, and with available screening
      mammograms. Mammograms were coded by three radiologists for presence or absence
      of BAC. History of coronary heart disease (CHD), stroke, and diabetes and risk
      factors for cardiovascular disease (including smoking status, body mass index
      [BMI], blood pressure, diabetes, and glycosylated hemoglobin [HbA1c]) were
      independently measured from health examinations in the EPIC study. RESULTS: The
      prevalence of BAC was 16.0%. Women with BAC were significantly older than those
      without it. BAC was associated with prevalent CHD, but not stroke. The odds ratio
      of having CHD was 2.54 (95% confidence interval, 1.03-6.30). The sensitivity and
      specificity were 32.4% and 85.5%, respectively. Except for smoking, which showed
      an inverse association, there was no consistent significant association of BAC
      with cardiovascular disease risk factors including BMI, diabetes, HbA1c, or
      lipids. CONCLUSION: BAC found on mammograms was associated with prevalent CHD
      after adjustment for age, but with low sensitivity. BAC may provide additional
      information toward identifying cardiovascular disease risk among otherwise
      healthy women.

PMID- 16794159
TI  - Unexpected focal hypermetabolic activity in the breast: significance in patients
      undergoing 18F-FDG PET/CT.
AB  - OBJECTIVE: We describe the significance of detecting focal areas of
      hypermetabolism in the breast in patients undergoing PET/CT for reasons other
      than for breast cancer detection or staging. CONCLUSION: When evaluated, almost
      all of the abnormal foci detected in the breast subsequently proved to be breast
      carcinoma, specifically infiltrating ductal carcinoma.

PMID- 16794160
TI  - Evaluation of pain in three hysterosalpingography techniques: metal cannula with
      and without paracervical blockage and balloon catheter.
AB  - OBJECTIVE: The objective of this study was to assess discomfort or pain in
      patients undergoing hysterosalpingography using three different techniques.
      SUBJECTS AND METHODS: Eighty-nine patients were randomly assigned to one of three
      groups. In group 1, 30 patients underwent the technique performed with a metal
      cannula without anesthetic; in group 2, 29 patients underwent the technique
      performed with a metal cannula with previous paracervical anesthetic block; in
      group 3, 30 patients submitted to the procedure performed with a flexible balloon
      catheter. Each patient completed two questionnaires, Q1 and Q2: Q1 assessed their
      personal, clinical, and surgical history, and Q2 provided the visual analog scale
      (VAS) for pain assessment. The investigator also evaluated discomfort at each
      potentially painful stage of the procedure based on the patient's verbal
      expression, physical manifestations, or both. RESULTS: In terms of global
      discomfort experienced during hysterosalpingography, group 1 had the highest mean
      VAS score, whereas scores did not significantly differ between groups 2 and 3.
      During cervical grasping, group 2 experienced less discomfort than group 1. A
      comparison of pain associated with cervical grasping and balloon inflation (group
      3 only) revealed that the highest levels of discomfort occurred during cervical
      grasping without anesthesia (group 1), followed by balloon inflation inside the
      cervix (group 3), and, last, cervical grasping after paracervical block (group
      2). CONCLUSION: Performing hysterosalpingography with a flexible balloon catheter
      or metal cannula with previous paracervical block produced similar levels of
      pain; however, both techniques appear to be more comfortable than the traditional
      technique (i.e., metal cannula without anesthesia).

PMID- 16794162
TI  - Recurrent ovarian cancer: spectrum of imaging findings.
AB  - OBJECTIVE: The purpose of this article is to show the appearance of atypical
      sites of metastasis in patients with recurrent ovarian cancer. CONCLUSION:
      Metastatic disease from ovarian cancer outside of the peritoneal cavity is
      generally rare at presentation but is increasingly seen in patients who have
      recurrent disease, despite multiple therapies. It is important for radiologists
      to recognize atypical sites of metastasis in patients with recurrent ovarian
      cancer to facilitate earlier diagnosis and treatment.

PMID- 16794161
TI  - Transvaginal sonography as an adjunct to endorectal sonography in the staging of
      rectal cancer in women.
AB  - OBJECTIVE: The purpose of this study was to evaluate the contribution of
      transvaginal sonography (TVS) in the staging of rectal cancer in women. MATERIALS
      AND METHODS: Sixty women with rectal tumors underwent TVS. Forty-five of the 60
      women also underwent endorectal sonography. Forty-nine of the women had rectal
      carcinoma; nine, tubulovillous adenoma; and two, gastrointestinal stromal tumor
      confirmed at surgical pathologic examination (n = 41) and biopsy before
      chemoradiation therapy (n = 19). Four of the 49 rectal carcinomas were T1; seven,
      T2; 35, T3; and three, T4. Images from TVS and endorectal sonography were shown
      independently to two blinded reviewers, who staged the tumors and assessed
      examination adequacy for tumor presence, size, and depth and nodal status.
      Staging results with TVS were compared with those obtained with endorectal
      sonography and histopathologic examination. RESULTS: All tumors were seen with
      TVS. In 30 of the 49 rectal carcinomas confirmed at surgical pathologic
      examination TVS tumor staging was accurate in 25 (83.3%) of the cases. Two (6.7%)
      of the 30 tumors were understaged, and 3 (10%) were overstaged. All tumors
      selected for chemoradiation (n = 19) were correctly staged T3. Endorectal
      sonography was suboptimal for tumors that were stenotic (n = 3), large (n = 2),
      high at the rectosigmoid junction (n = 4), or low at the anal canal (n = 3). In
      these 12 cases, TVS successfully depicted the lesion, and the images gave enough
      information for prediction of stage. In interpretation of the images of 45
      patients who underwent both TVS and endorectal sonography, the blinded reviewers
      had good agreement and comparable accuracy for staging in adequate examinations
      with each technique. Four of the nine villous adenomas were overstaged as T1 on
      TVS. Gastrointestinal stromal tumors manifested as intramural vascular masses.
      CONCLUSION: TVS is an excellent adjunct to endorectal sonography in the staging
      of rectal cancer in women. It helps resolve the findings after endorectal
      sonography has been unsuccessful because the tumors are stenotic or in a high or
      low position.

PMID- 16794163
TI  - Coronary artery imaging with contrast-enhanced MDCT: extracardiac findings.
AB  - OBJECTIVE: The purpose of our study was to evaluate the incidence of extracardiac
      findings on contrast-enhanced MDCT of the coronary arteries and to assess the
      effect of different field-of-view settings. SUBJECTS AND METHODS: Patients with
      suspected coronary artery disease (n = 166) were examined with contrast-enhanced
      MDCT (16 x 0.75 mm focused on the heart) during injection of contrast material
      (80 mL injected at a rate of 4 mL/sec) followed by saline (20 mL injected at 4
      mL/sec). Retrospectively gated images were reconstructed at a 1-mm slice
      thickness and a 0.5-mm increment with isotropic voxels of 1 mm3. Images were
      reviewed for extracardiac findings, which were then classified as none, minor, or
      major with respect to their impact on patient management and treatment. In a
      different group of patients (n = 20), chest scans (16 x 1.5 mm) were used for
      measuring volumes of displayed body structures on wholechest scans, coronary
      artery MDCT images, and coronary artery MDCT images reconstructed with the
      maximum field of view. RESULTS: Extracardiac findings were detected in 41
      patients (24.7%). Findings were classified as minor (19.9%) or major (4.8%).
      Among the major findings, which had an immediate impact on patient management and
      treatment, were bronchial carcinoma and pulmonary emboli. Volume analysis
      revealed that 35.5% of the total chest volume was displayed on dedicated coronary
      artery MDCT focused on the heart, whereas 70.3% of the chest was visible when
      coronary artery MDCT raw data were reconstructed with the maximal field of view
      (p < 0.001). CONCLUSION: Coronary artery MDCT can reveal important findings and
      disease in extracardiac structures. Thus, the entire examination should be
      reconstructed with the maximum field of view and should be reviewed by a
      qualified radiologist.

PMID- 16794165
TI  - Coronary CT angiography with 64-MDCT: assessment of vessel visibility.
AB  - OBJECTIVE: The objective of our study was to evaluate the image quality of 64
      MDCT for coronary angiography. SUBJECTS AND METHODS: Fifty consecutive CT
      coronary angiograms obtained on a 64-MDCT scanner were independently reviewed by
      two reviewers. Segments were scored as showing no motion (score of 1), minimal
      motion (2), moderate motion (3), respiratory motion (4), or vessel blurring (5).
      Opacification was graded as good (score of 1) or limited (2). Segments < 2 mm
      were graded as well seen; or as poorly seen or not seen. The scores for motion
      artifact, opacification, and visibility were combined for overall vessel
      assessment. Segments with a motion score of 1 or 2 that had good opacification
      and were well seen were judged to be assessable. RESULTS: A total of 714 segments
      were analyzed in 50 patients. Seven hundred segments were assessed in all
      patients (segments 1-3, 11-20, 4, or 27), and a ramus intermedius segment was
      evaluated in 14 patients. Combining the scores for both reviewers, the average
      motion score was 1 for 619 segments (86.7%), the average motion score for all
      segments in an individual patient was 1.14 (range, 1-3.35), and the average
      opacification score for all segments in a patient was 1.02 (range, 1-1.38). A
      total of 374 segments were less than 2 mm in diameter. Combining the scores for
      both reviewers, an average of 36 segments (5.0% of 714) could not be identified
      by the reviewers, 319.5 segments (85.4%) were well seen, and 18.5 segments (4.9%)
      were poorly seen. Overall, an average of 637 segments (89.2%) were judged
      assessable by the reviewers. On a per-patient basis, 10 or more vessel segments
      were judged assessable in 47 patients (94%). CONCLUSION: On 64-MDCT, 89% of
      coronary artery segments are assessable. Ten or more vessel segments are
      assessable in 94% of patients.

PMID- 16794164
TI  - Accuracy of 64-MDCT in the diagnosis of ischemic heart disease.
AB  - OBJECTIVE: The aim of this study was to evaluate the potential clinical value of
      a new generation of 64-MDCT systems with that of invasive coronary angiography in
      the diagnosis of coronary artery disease (CAD). SUBJECTS AND METHODS: Seventy-two
      consecutive patients with known or suspected CAD underwent both 64-MDCT and
      quantitative coronary angiography (QCA). A CT system with acquisition of 64
      slices per gantry rotation was used with a spatial resolution of 0.4 x 0.4 x 0.4
      mm and a gantry rotation time of 330 milliseconds. Sensitivity, specificity, and
      diagnostic accuracy of 64-MDCT in the detection or exclusion of CAD were
      evaluated on both a per patient and a per segment basis. RESULTS: Sixty-eight of
      72 coronary CT angiograms (CTAs) (94%) were of diagnostic image quality. QCA
      showed significant CAD (i.e., one or more stenoses in > 50%) in 57% (39/68) and
      nonsignificant disease or healthy CTAs in 43% (29/68) of the patients.
      Sensitivity, specificity, and the negative predictive value (NPV) of 64-MDCT per
      patient were 97%, 79%, and 96%, respectively. Per segment, 923 of 1,020 coronary
      artery segments were assessable (90%). For the detection of stenoses of more than
      50% and more than 75% per segment, 64-MDCT showed a sensitivity of 82% and 86%,
      respectively. Per segment, specificity and NPV were as high as 95% and 97%,
      respectively. CONCLUSION: In clinical routine, coronary CTA will primarily be
      used for risk stratification on a per patient basis. In the present study,
      coronary 64-MDCT showed a high diagnostic accuracy on both per patient and per
      segment analyses.

PMID- 16794166
TI  - Hemodynamic effects of monomeric nonionic contrast media in pulmonary angiography
      in chronic thromboembolic pulmonary hypertension.
AB  - OBJECTIVE: The purpose of this study was to investigate the hemodynamic safety of
      the monomeric nonionic contrast agent iomeprol for selective pulmonary
      angiography in chronic thromboembolic pulmonary hypertension (CTPH), and to
      investigate the effect of periinterventional oxygen administration. SUBJECTS AND
      METHODS: Selective pulmonary digital subtraction angiography was performed in 94
      patients with CTPH using six bolus injections of iomeprol (posteroanterior,
      oblique, and lateral projections; both pulmonary arteries; iomeprol, 25 mL at 13
      mL/s). Hemodynamics were obtained with Swan-Ganz catheters, and systolic
      pulmonary artery pressure (PAsyst) was classified into one of three groups: 30 mm
      Hg or less (control group), greater than 30 but less than or equal to 60 mm Hg
      (group 1, moderate pulmonary hypertension), and greater than 60 mm Hg (group 2,
      severe pulmonary hypertension). RESULTS: At baseline, values for PAsyst were 21.4
      +/- 2.3 (control group, n = 8), 49.8+/- 8.5 (group 1, n = 18), and 86.5 +/- 18.9
      (group 2, n = 68) mm Hg (p < 0.001). Pulmonary vascular resistance indexes (PVRI)
      were 222 +/- 105 (control), 703 +/- 364 (group 1), and 1,582 +/- 562 (group 2)
      dyne x s x cm(-5) x m2 (p < 0.001). The mean cardiac indexes were 3.1 (control),
      2.8 (group 1), and 2.3 (group 2) L/min/m2 (p < 0.05). Pulmonary capillary wedge
      pressure (PCw) indicated healthy left heart function. Periinterventional oxygen
      inhalation improved oxygen saturation in all groups and slightly reduced
      pulmonary artery pressure and heart rate. Online measurement of pulmonary artery
      pressure during contrast bolus injection for angiography showed only a minor
      increase, predominantly in severe pulmonary hypertension (triangle up
      [difference] PAsyst: 1.3 +/- 1.9 [control], 2.9 +/- 3.4 [group 1], and 3.8 +/-
      4.5 [group 2] mm Hg [p < 0.001]). After completion of angiography, right atrial
      pressure (RAP) and PAsyst were moderately increased: triangle up RAP: 1.4
      (control), 2.6 (group 1, p < 0.001), and 3.0 (group 2, p < 0.001) mm Hg; triangle
      up PAsyst: 3.2 (control), 7.7 (group 1, p < 0.01), and 8.5 (group 2) mm Hg (p <
      0.001). PVRI was significantly higher in group 2 (triangle up PVRI: 188 dyne x s
      x cm(-5) x m2, p < 0.001). CONCLUSION: Selective pulmonary angiography using
      iomeprol is safe without critical pressure peaks during selective contrast bolus
      injection or significant hemodynamic derangement in severe CTPH.
      Periinterventional oxygen inhalation improved pulmonary circulation.

PMID- 16794168
TI  - Management of patients with small pulmonary nodules: a survey of radiologists,
      pulmonologists, and thoracic surgeons.
AB  - OBJECTIVE: The objective of our study was to survey recommendations for the
      management of small pulmonary nodules found on helical CT from radiologists,
      pulmonologists, and thoracic surgeons. MATERIALS AND METHODS: We surveyed 774
      radiologists, 623 pulmonologists, and 101 thoracic surgeons. All are members of
      an associated Austrian scientific society and were asked for their
      recommendations in 13 hypothetical cases. Statistical analysis was focused on
      possible differences between medical specialities, residents and fellows, and
      male and female doctors and on a possible influence of the number of years in
      training or in medical practice. RESULTS: Complete surveys were returned from 91
      radiologists, 74 pulmonologists, and 12 thoracic surgeons. The most frequent
      recommendation from radiologists was follow-up, whereas the most frequent
      recommendation from pulmonologists and surgeons was biopsy. The most frequently
      advised CT follow-up period was 3 months. Whereas thoracic surgeons preferred
      video-assisted thoracoscopy, radiologists and pulmonologists recommended less
      invasive procedures (bronchoscopy, CT-guided biopsy) to gain a specific
      diagnosis. CONCLUSION: There are significant differences in the management of
      small pulmonary nodules among radiologists, pulmonologists, and thoracic
      surgeons. Whereas radiologists tend to recommend short-term follow-up,
      pulmonologists and thoracic surgeons prefer a more aggressive approach,
      especially in patients with a higher likelihood of malignancy.

PMID- 16794169
TI  - 16-MDCT and MR angiography of accessory diaphragm.

PMID- 16794170
TI  - Value of delayed imaging in MDCT of the abdomen and pelvis.
AB  - OBJECTIVE: Our objective was to illustrate the benefits of obtaining delayed CT
      images. CONCLUSION: There are several clinical scenarios in which delayed CT
      images may improve diagnostic specificity.

PMID- 16794167
TI  - Software volumetric evaluation of doubling times for differentiating benign
      versus malignant pulmonary nodules.
AB  - OBJECTIVE: The purpose of our study was to evaluate the reliability of software
      calculated doubling times for discerning malignant versus benign nodules.
      MATERIALS AND METHODS: CT lung analysis volumetric software was used to
      retrospectively calculate the doubling times of 63 solid noncalcified nodules by
      comparing nodule volumes on baseline and follow-up CT scans obtained a median of
      3.7 months apart. A final diagnosis based on validated criteria was available for
      all 63 nodules. All CT examinations were performed with 1.25-mm-thick slices on a
      four-detector unit. Taking 500 days as the upper value for malignancies, we
      evaluated whether the software-calculated doubling times could be used to
      distinguish malignant from benign solid nodules. We also examined whether the
      relative volume variation of benign nodules correlated with initial nodule size,
      interscan interval, or differences in contrast administration or exposure
      parameters between baseline and follow-up CT. RESULTS: There were 52 benign and
      11 malignant nodules. Benign nodules had a median doubling time of 947 days and a
      mean relative volume variation of -4.4% (range, -50% to 38%). Malignant nodules
      had a median doubling time of 117 days and a mean relative volume variation of
      102% (22-462%). The sensitivity, specificity, and negative and positive
      predictive values of the volumetric software for diagnosing malignancy were 91%
      (95% confidence interval [CI], 0.59-1.00), 90% (95% CI, 0.79-0.97), 98% (95% CI,
      0.89-1.00), and 67% (95% CI, 0.38-0.88), respectively. No correlation was found
      between the relative volume variation of benign nodules and their initial size,
      the interscan interval, or differences in contrast administration or exposure
      parameters between the two CT examinations. CONCLUSION: Software-calculated
      pulmonary nodule doubling times of more than 500 days have a 98% negative
      predictive value for the diagnosis of solid malignant pulmonary nodules. This
      method may be useful for diagnosing malignant pulmonary nodules on follow-up CT.

PMID- 16794172
TI  - Double-contrast barium enema: use in practice and implications for CT
      colonography.
AB  - OBJECTIVE: This study examines the use and yield of double-contrast barium enemas
      (DCBEs) for colorectal polyp detection in current clinical practice outside the
      research setting. MATERIALS AND METHODS: My colleagues and I retrospectively
      reviewed adult DCBE studies performed in routine clinical practice at a single
      academic institution from 2001 through 2004 by reviewing the official radiology
      and colonoscopy reports. Data were collected on indications for a DCBE, number of
      positive and negative DCBE reports, results of a DCBE after failed colonoscopy,
      and professional profiles of the radiologists who performed the DCBEs.
      Correlation for colon polyp detection was made by reviewing reports of
      colonoscopy performed within 12 months before or after a DCBE. Polyp detection
      and matching analysis used a six-segment colon localization scheme. RESULTS: A
      total of 244 out of 665 (36.7%) barium enema studies were performed using the
      double-contrast technique over the 4-year period-that is, approximately one per
      week. The most common indication for a DCBE (109/244 or 44.6%) was to complete a
      failed, incomplete, or inconclusive colonoscopy. Overall, only 14 of the 244
      (5.7%) studies gave positive reports for polyps, and of these, five were shown to
      be false-positive at later colonoscopy. Only six polyps 10 mm or larger were
      positively detected during the entire study, which is approximately one per 60
      studies or one every 8 months. In 104 patients who had negative DCBEs after
      failed or inconclusive colonoscopy, more than 50 subcentimeter polyps had been
      detected and removed, yet not one additional polyp was detected by a DCBE. Of the
      15 radiologists performing the DCBEs during the study period, 89.7% of the
      studies were done by four individuals. Three of these four radiologists were
      older than 60 years at the beginning of the study, and two of them are now either
      retired or no longer perform fluoroscopy. CONCLUSION: In our center, a DCBE is a
      low-yield procedure for detecting polyps, with a high false-positive rate, and is
      not likely to be performed by experienced practitioners in the future.

PMID- 16794171
TI  - Quantitative assessment of tissue perfusion using MDCT: comparison of colorectal
      cancer and skeletal muscle measurement reproducibility.
AB  - OBJECTIVE: The purposes of this study were to determine the reproducibility of
      quantitative colorectal cancer perfusion measurements using dynamic contrast
      enhanced MDCT, and to compare this with measurements from skeletal muscle.
      SUBJECTS AND METHODS: Ten patients (mean age, 67 years; six men, four women) with
      histologically proven colorectal cancer were examined prospectively using 4-MDCT.
      Perfusion studies (cine mode; 4 x 5 mm collimation; 1 acquisition/s; 65 seconds
      total) were performed through the tumor epicenter after IV bolus contrast
      administration (iopamidol 340, 100 mL; 5 mL/s) and repeated within 48 hours.
      Quantitative values for blood volume, blood flow, mean transit time, and
      permeability were determined using commercial software. Two regions of interest
      were studied on the axial image: one within the tumor and another within the left
      gluteal muscle. Measurement reproducibility was assessed using Bland-Altman
      statistics. RESULTS: For the tumor, the mean difference (95% limits of agreement)
      was -0.04 mL/100 g tissue (-2.50, 2.42); 8.80 (-50.5, 68.0) mL/100 g tissue/min; 
      0.99 (-8.19, 6.20) seconds; and 1.20 (-5.42, 7.83) mL/100 g tissue/min for blood
      volume, blood flow, mean transit time, and permeability, respectively. For
      muscle, the mean difference (95% limits of agreement) was 0.02 (-1.40, 1.43),
      6.60 (-11.2, 24.3), -3.76 (-16.87, 9.35), and 1.30 (-4.68, 7.28), respectively.
      CONCLUSION: Quantitative perfusion measurements are reproducible. Measurements
      from tumor are less variable than from skeletal muscle.

PMID- 16794173
TI  - Accuracy of MDCT in the diagnosis of choledocholithiasis.
AB  - OBJECTIVE: Our purpose was to evaluate the diagnostic performance of contrast
      enhanced and unenhanced MDCT, performed for various indications, in detecting
      choledocholithiasis. CONCLUSION: Unenhanced and contrast-enhanced MDCT images,
      interpreted in PACS workstations with axial images, are moderately sensitive and
      specific for showing choledocholithiasis.

PMID- 16794174
TI  - High-B-value diffusion-weighted MRI in colorectal cancer.
AB  - OBJECTIVE: The purpose of this article is to evaluate the usefulness of high-b
      value diffusion-weighted MRI (DW-MRI) in the detection of colorectal
      adenocarcinoma. CONCLUSION: High-b-value DW-MRI allows detection of colorectal
      adenocarcinoma with a high sensitivity and specificity.

PMID- 16794175
TI  - Sonography of inguinal region hernias.
AB  - OBJECTIVE: The purpose of this article is to describe the anatomy of the inguinal
      region in a way that is useful for sonographic diagnosis of inguinal region
      hernias, and to illustrate the sonographic appearance of this anatomy. We show
      sonographic techniques for evaluating inguinal, femoral, and spigelian hernias
      and include surgically proven examples. CONCLUSION: Understanding healthy
      inguinal anatomy is essential for diagnosing inguinal region hernias. Sonography
      can diagnose and differentiate between various inguinal region hernias.

PMID- 16794176
TI  - CT histogram analysis in pathologically proven adrenal masses.
AB  - OBJECTIVE: The purpose of this article is to evaluate a histogram analysis method
      for distinguishing adrenal adenomas from metastases, pheochromocytomas, and
      adrenocortical carcinomas on CT. MATERIALS AND METHODS: A pathology database was
      searched, and 335 adrenalectomies from 1995 to 2002 were identified. CT images
      were available for retrospective review in 187 patients (93 males, 94 females;
      age range, 15-84 years; mean age, 55.2 years) with 208 adrenal masses. This
      included 112 adenomas in 104 patients, 48 metastases in 39 patients, 40
      pheochromocytomas in 36 patients, and eight adrenocortical carcinomas in eight
      patients. Histogram analysis was performed using a circular region of interest
      for mean attenuation, number of pixels, number of negative pixels (< 0 H), and
      percentage of negative pixels by two interpreters. Areas of necrosis were
      excluded from measurements. Observer agreement was calculated. RESULTS: In 72 of
      76 (94.7%) and 63 of 72 (87.5%) adenomas, respectively, interpreters found
      attenuation values greater than 10 H contained negative pixels on unenhanced CT
      scans. None of the enhanced adenomas had mean attenuation less than or equal to
      10 H, but 24 (38.7%) and 28 (45.2%), respectively, had negative pixels. Negative
      pixels were present in unenhanced and enhanced metastases, pheochromocytomas, and
      carcinomas. Using a 5% or 10% negative pixel threshold value to diagnose adenoma
      improved specificity but diminished sensitivity. Specificity for a 10% negative
      pixel threshold was approximately 88% for unenhanced CT scans and 99% for
      enhanced CT scans, with sensitivities of 71% and 12%, respectively. CONCLUSION:
      Although specificity for the diagnosis of adenomas on enhanced CT scans with
      histogram analysis was high when a 10% negative pixel threshold was used, low
      sensitivity likely limits clinical usefulness.

PMID- 16794177
TI  - Optimal scan window for detection of hypervascular hepatocellular carcinomas
      during MDCT examination.
AB  - OBJECTIVE: The purpose of this study was to define the optimal scan window for
      acquiring arterial phase images in the detection of hypervascular hepatocellular
      carcinomas (HCCs). MATERIALS AND METHODS: Biphasic arterial phase CT examinations
      were performed using a 16-MDCT scanner on 198 patients (159 men and 39 women;
      mean age, 59 years; age range, 25-82 years) with nodular HCC. All examinations
      were performed after administering 120-150 mL of a nonionic contrast media (370
      mg I/mL) at a rate of 3-4 mL/s. The scan delay--the interval between when the
      bolus-tracking program detected the threshold enhancement of 100 H in the
      abdominal aorta and the start of the first arterial scan-was progressively
      lengthened by 2-second intervals, from 10 seconds in group 1 to 20 seconds in
      group 6. The second arterial phase scan was started 6 seconds after the end of
      the early scan. A tube collimation of 1.5 mm, a table feed of 18 mm per rotation,
      an image thickness of 3 mm, and 3-mm increments were used. The duration of each
      phase scan was 4.5-8.8 seconds. Tumor-to-liver attenuation difference (TLAD) at
      the first (TLAD1) and second (TLAD2) arterial phase images were compared lesion
      by lesion. Four observers assigned subjective ratings of visual conspicuity and
      individual preferences for each phase in each group. RESULTS: The mean threshold
      time (100 H) was 18.4 +/- 3.1 seconds, and 97% of patients were within the range
      of 13-24 seconds. The mean TLAD1 of groups 3 to 6 and the mean TLAD2 of groups 1
      to 5 were all comparable; they were also all significantly (p < 0.005) higher
      than the mean TLAD1 of groups 1 and 2 and the mean TLAD2 of group 6. In groups 1
      and 2, the mean TLAD2 was significantly higher than the mean TLAD1 (p < 0.001);
      in groups 5 and 6, the mean TLAD1 was significantly higher than the mean TLAD2 (p
      < 0.001). In groups 3 and 4, the mean TLAD1 and TLAD2 were similar. The visual
      conspicuity and individual preferences were higher for the first-phase image in
      groups 3 to 6 and the second-phase image in groups 1 and 2. CONCLUSION: The
      optimal scan window for arterial phase images in the detection of HCC seems to be
      approximately 14-30 seconds from the 100-H threshold.

PMID- 16794178
TI  - Postmortem radiology of fatal hemorrhage: measurements of cross-sectional areas
      of major blood vessels and volumes of aorta and spleen on MDCT and volumes of
      heart chambers on MRI.
AB  - OBJECTIVE: Autopsy determination of fatal hemorrhage as the cause of death is
      often a difficult diagnosis in forensic medicine. No quantitative system for
      accurately measuring the blood volume in a corpse has been developed. MATERIALS
      AND METHODS: This article describes the measurement and evaluation of the cross
      sectional areas of major blood vessels, of the diameter of the right pulmonary
      artery, of the volumes of thoracic aorta and spleen on MDCT, and of the volumes
      of heart chambers on MRI in 65 autopsy-verified cases of fatal hemorrhage or no
      fatal hemorrhage. RESULTS: Most cases with a cause of death of "fatal hemorrhage"
      had collapsed vessels. The finding of a collapsed superior vena cava, main
      pulmonary artery, or right pulmonary artery was 100% specific for fatal
      hemorrhage. The mean volumes of the thoracic aorta and of each of the heart
      chambers and the mean cross-sectional areas of all vessels except the inferior
      vena cava and abdominal aorta were significantly smaller in fatal hemorrhage than
      in no fatal hemorrhage. CONCLUSION: For the quantitative differentiation of fatal
      hemorrhage from other causes of death, we propose a three-step algorithm with
      measurements of the diameter of the right pulmonary artery, the cross-sectional
      area of the main pulmonary artery, and the volume of the right atrium
      (specificity, 100%; sensitivity, 95%). However, this algorithm must be
      corroborated in a prospective study, which would eliminate the limitations of
      this study. Quantitative postmortem cross-sectional imaging might become a
      reliable objective method to assess the question of fatal hemorrhage in forensic
      medicine.

PMID- 16794179
TI  - Dynamic sonography evaluation of shoulder impingement syndrome.
AB  - OBJECTIVE: Our aim was to characterize shoulder impingement syndrome using
      dynamic sonography. CONCLUSION: Dynamic sonography allows direct visualization of
      the relationships between the acromion, humeral head, and intervening soft
      tissues during active shoulder motion and can provide useful information
      regarding potential intrinsic and extrinsic causes of shoulder impingement
      syndrome.

PMID- 16794180
TI  - Accuracy of 3-T MRI using fast spin-echo technique to detect meniscal tears of
      the knee.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of the fast
      spin-echo technique in detecting meniscal tears of the knee using a 3-T MRI
      system. CONCLUSION: We concluded from this study that 3-T MRI using fast spin
      echo sequences is highly accurate in the detection of medial and lateral meniscal
      tears of the knee.

PMID- 16794182
TI  - Imaging of cerebrovascular and cardiovascular disease in AIDS patients.
AB  - OBJECTIVE: The purpose of this article is to show the imaging findings in
      patients who have cerebrovascular and cardiovascular complications caused by
      AIDS. CONCLUSION: Detection of multifocal aneurysms, unexplained cardiomyopathy,
      and venous thrombosis in high-risk patients should suggest the possibility of
      AIDS.

PMID- 16794181
TI  - In vivo identification of complicated upper thoracic aorta and arch vessel plaque
      by MR direct thrombus imaging in patients investigated for cerebrovascular
      disease.
AB  - OBJECTIVE: The objective of this article was to assess the feasibility of MR
      direct thrombus imaging (MRDTI) to evaluate the prevalence and location of
      complicated upper thoracic aortic and arch vessel plaque in patients referred for
      evaluation of cerebrovascular disease. SUBJECTS AND METHODS: Patients referred
      for investigation of cerebrovascular disease by MRI were enrolled. Reasons for
      referral included transient ischemic attack/amaurosis fugax, acute infarct,
      remote infarct, or asymptomatic carotid disease. Of the 348 patients initially
      scanned, 17 were excluded from the analysis. The final patient population
      included 331 patients (199 men, 132 women; mean age, 67.7 years). Patients were
      scanned using MRDTI, a 3D, T1-weighted, fat-suppressed spoiled gradient echo that
      exploits the T1 shortening effects of methemoglobin, directly visualizing
      hemorrhage/thrombus in the vessel wall, thus identifying complicated plaque.
      Complicated plaque was defined as a high signal within the atherosclerotic plaque
      at least twice the signal intensity of muscle. RESULTS: Forty-three of 331
      patients (13%) had complicated upper thoracic aortic atherosclerotic disease,
      arch vessel atherosclerotic disease, or both. The upper thoracic aorta was
      involved in 36 of 43 patients (83.7%), and the left subclavian artery was
      involved in 14 of 43 patients (32.6%). Both the right subclavian artery and the
      brachiocephalic artery were involved in one of 43 patients (2.3%). Complicated
      carotid plaque was seen in 25 of 43 patients (58.1%). CONCLUSION: MRDTI can be
      applied in the detection of complicated plaque in the upper thoracic aorta and
      arch vessels. Complicated plaque was identified in 13% of the patient population.
      The upper thoracic aorta was the most common site involved. This technique could
      be useful for the screening of asymptomatic at-risk patients.

PMID- 16794183
TI  - Fluoroscopic contrast-enhanced MR angiography with a magnetization-prepared
      steady-state free precession technique in peripheral arterial occlusive disease.
AB  - OBJECTIVE: The objective of our study was to evaluate the feasibility of
      intraarterial (IA) near-real-time contrast-enhanced MR angiography (CE-MRA) with
      a frame rate of 1.3 frames per second in seven patients with lower extremity
      peripheral arterial occlusive disease (PAOD). For optimized background
      suppression, a modified 2D steady-state free precession (SSFP) technique with
      magnetization preparation and mask subtraction was developed. The femoropopliteal
      and infrapopliteal arteries were covered in two separate steps. Acceptable
      contrast-to-noise ratios were obtained, and road maps were reconstructed from the
      same data set. CONCLUSION: Mastering IA near-real-time CE-MRA, including road map
      reconstruction, with an SSFP technique in the lower extremity of patients with
      PAOD is an important building block toward successfully performing endovascular
      catheter MR-guided interventions.

PMID- 16794184
TI  - Sarcoplasmic reticulum and nuclear envelope are one highly interconnected Ca2+
      store throughout cardiac myocyte.
AB  - Previous ventricular myocyte studies indicated that ryanodine receptors (RyRs)
      are in the sarcoplasmic reticulum (SR) and are critical in excitation-contraction
      coupling, whereas the inositol trisphosphate (InsP(3)) receptors are separately
      localized on the nuclear envelope (NucEn) and involved in nuclear Ca(2+)
      signaling. Here, we find that both caffeine and InsP(3) receptor agonists deplete
      free [Ca(2+)] inside both SR and NucEn. Fluorescence recovery after photobleach
      (FRAP) was measured using the low-affinity Ca(2+) indicator Fluo-5N trapped
      inside the SR and NucEn (where its fluorescence is high because [Ca(2+)] is &1
      mmol/L). After Fluo-5N photobleach in one end of the cell, FRAP occurred,
      accompanied by fluorescence decline in the unbleached end with similar time
      constants (tau&2 minutes) until fluorescence regained spatial uniformity.
      Notably, SR and NucEn fluorescence recovered simultaneously in the bleached end.
      Ca(2+) diffusion inside the SR-NucEn was also measured. SR Ca(2+)-ATPase was
      completely blocked but without acute SR Ca(2+) depletion. Then caffeine was
      applied locally to one end of the myocyte. In the caffeine-exposed end, free SR
      [Ca(2+)] ([Ca(2+)](SR)) declined abruptly and recovered partially (tau=20 to 30
      seconds). In the noncaffeine end, [Ca(2+)](SR) gradually declined with a similar
      tau, until [Ca(2+)](SR) throughout the cell equalized. We conclude that the SR
      and NucEn lumen are extensively interconnected throughout the myocyte. Apparent
      intrastore diffusion coefficients of Fluo-5N and Ca(2+) were estimated (&8
      microm(2) sec(-1) and 60 microm(2) sec(-1)). This rapid luminal communication may
      maintain homogeneously high luminal [Ca(2+)], ensuring a robust and uniform
      driving force for local Ca(2+) release events from either SR or NucEn.

PMID- 16794185
TI  - Paclitaxel enhances thrombin-induced endothelial tissue factor expression via c
      Jun terminal NH2 kinase activation.
AB  - Paclitaxel is used on drug-eluting stents because it inhibits proliferation of
      vascular cells. Stent thrombosis remains a concern with this compound,
      particularly with higher dosages. This study investigates the effect of
      paclitaxel on tissue factor (TF) expression in human endothelial cells.
      Paclitaxel enhanced thrombin-induced endothelial TF protein expression in a
      concentration- and time-dependent manner. A concentration of 10(-5) mol/L
      elicited a 2.1-fold increase in TF protein and a 1.6-fold increase in TF surface
      activity. The effect was similar after a 1 hour as compared with a 25-hour
      pretreatment period. Real-time polymerase chain reaction revealed that paclitaxel
      increased thrombin-induced TF mRNA expression. Paclitaxel potently activated c
      Jun terminal NH2 kinase (JNK) as compared with thrombin alone, whereas the
      thrombin-mediated phosphorylation of p38 and extracellular signal-regulated
      kinase remained unaffected. Similar to paclitaxel, docetaxel enhanced both TF
      expression and JNK activation as compared with thrombin alone. The JNK inhibitor
      SP600125 reduced thrombin-induced TF expression by 35%. Moreover, SP600125
      blunted the effect of paclitaxel and docetaxel on thrombin-induced TF expression.
      Paclitaxel increases endothelial TF expression via its stabilizing effect on
      microtubules and selective activation of JNK. This observation provides novel
      insights into the pathogenesis of thrombus formation after paclitaxel-eluting
      stent deployment and may have an impact on drug-eluting stent design.

PMID- 16794186
TI  - A zebrafish model of human Barth syndrome reveals the essential role of tafazzin
      in cardiac development and function.
AB  - Barth syndrome is an X-linked disorder characterized by cardiomyopathy, skeletal
      myopathy, neutropenia, organic aciduria, and growth retardation caused by
      mutations in tafazzin. The sequence similarity of tafazzin to acyltransferases
      suggests a role in mitochondrial phospholipid metabolism. To study the role of
      tafazzin in heart function and development, we created a knockdown zebrafish
      model. Zebrafish tafazzin mRNA is first evident at 7 hours post-fertilization
      (hpf). At 10 and 24 hpf, tafazzin mRNA is ubiquitous, with highest levels in the
      head. By 51 hpf, expression becomes cardiac restricted. The tafazzin knockdown
      created by antisense morpholino yolk injection resulted in dose-dependent
      lethality, severe developmental and growth retardation, marked bradycardia and
      pericardial effusions, and generalized edema, signs that resemble human Barth
      syndrome heart failure. This knockdown phenotype was rescued by concomitant
      injection of normal tafazzin mRNA. Abnormal cardiac development, with a linear,
      nonlooped heart, and hypomorphic tail and eye development proves that tafazzin is
      essential for overall zebrafish development, especially of the heart. The
      tafazzin knockdown zebrafish provides an animal model similar to Barth syndrome
      to analyze the severity of human mutants and to test potential treatments.

PMID- 16794187
TI  - 2-Methoxyestradiol, an estradiol metabolite, inhibits neointima formation and
      smooth muscle cell growth via double blockade of the cell cycle.
AB  - 2-Methoxyestradiol (2-ME), an endogenous metabolite of estradiol with no affinity
      for estrogen receptors, is a potent anticarcinogenic agent (in phase II clinical
      trials) and mediates the inhibitory effects of estradiol on smooth muscle cell
      (SMC) growth. Here we studied the intracellular mechanisms by which 2-ME inhibits
      SMC growth and whether 2-ME prevents injury-induced neointima formation. 2-ME
      concentrations that inhibit proliferation of cycling human aortic SMCs by >or=50%
      blocked cell-cycle progression in G(0)/G(1) and in G(2)/M phase, as determined by
      flow cytometry. Consistent with the cell-cycle effects, at a molecular level
      (Western blots), 2-ME inhibited cyclin D(1) and cyclin B(1) expression; cyclin
      dependent kinase (cdk)-1 and cdk-2 activity; and retinoblastoma protein (pRb),
      extracellular signal-regulated kinase (ERK) 1/2, and Akt phosphorylation. 2-ME
      also upregulated the Cdk inhibitor p27 and interfered with tubulin
      polymerization. Moreover, 2-ME augmented COX-2 expression, suggesting that it may
      also inhibit SMC growth via prostaglandin formation. In rats, treatment with 2-ME
      abrogated injury-induced neointima formation; decreased proliferating SMCs;
      downregulated expression of proliferating-cell nuclear antigen (PCNA), c-myc,
      cyclin D(1), cyclin B(1), phosphorylated Akt, phosphorylated ERK1/2, p21, and
      pRb; inhibited cdk-1 and cdk-4 activity; and upregulated expression of
      cyclooxygenase (COX)-2 and p27. Caspase-3 cleavage assay and fluorescence
      activated cell-sorting (FACS) analysis showed no evidence of apoptosis in 2-ME
      treated SMCs, and TUNEL staining in carotid segments showed no evidence of 2-ME
      induced apoptosis in vivo. The antimitotic effects of 2-ME on SMCs are mediated
      by the inhibition of key cell-cycle regulatory proteins and effects on tubulin
      polymerization and COX-2 upregulation. These effects of 2-ME most likely
      contribute to the antivasoocclusive actions of this endogenous compound.

PMID- 16794188
TI  - Activation of the unfolded protein response in infarcted mouse heart and hypoxic
      cultured cardiac myocytes.
AB  - Endoplasmic reticulum (ER) stresses that reduce ER protein folding activate the
      unfolded protein response (UPR). One effector of the UPR is the transcription
      factor X-box binding protein-1 (XBP1), which is expressed on ER stress-mediated
      splicing of the XBP1 mRNA. XBP1 induces certain ER-targeted proteins, eg, glucose
      regulated protein 78 (GRP78), that help resolve the ER stress and foster cell
      survival. In this study, we determined whether hypoxia can activate the UPR in
      the cardiac context. Neonatal rat ventricular myocyte cultures subjected to
      hypoxia (16 hours) exhibited increased XBP1 mRNA splicing, XBP1 protein
      expression, GRP78 promoter activation, and GRP78 protein levels; however, the
      levels of these UPR markers declined during reoxygenation, suggesting that the
      UPR is activated during hypoxia but not during reoxygenation. When cells were
      infected with a recombinant adenovirus (AdV) encoding dominant-negative XBP1 (AdV
      XBP1dn), UPR markers were reduced; however, hypoxia/reoxygenation-induced
      apoptosis increased. Confocal immunocytofluorescence demonstrated that hypoxia
      induced GRP78 in neonatal rat and isolated adult mouse ventricular myocytes.
      Moreover, mouse hearts subjected to in vivo myocardial infarction exhibited
      increased GRP78 expression in cardiac myocytes near the infarct, but not in
      healthy cells distal to the infarct. These results indicate that hypoxia
      activates the UPR in cardiac myocytes and that XBP1-inducible proteins may
      contribute to protecting the myocardium during hypoxic stress.

PMID- 16794190
TI  - Vascular smooth muscle cells undergo telomere-based senescence in human
      atherosclerosis: effects of telomerase and oxidative stress.
AB  - Although human atherosclerosis is associated with aging, direct evidence of
      cellular senescence and the mechanism of senescence in vascular smooth muscle
      cells (VSMCs) in atherosclerotic plaques is lacking. We examined normal vessels
      and plaques by histochemistry, Southern blotting, and fluorescence in situ
      hybridization for telomere signals. VSMCs in fibrous caps expressed markers of
      senescence (senescence-associated beta-galactosidase [SAbetaG] and the cyclin
      dependent kinase inhibitors [cdkis] p16 and p21) not seen in normal vessels. In
      matched samples from the same individual, plaques demonstrated markedly shorter
      telomeres than normal vessels. Fibrous cap VSMCs exhibited markedly shorter
      telomeres compared with normal medial VSMCs. Telomere shortening was closely
      associated with increasing severity of atherosclerosis. In vitro, plaque VSMCs
      demonstrated morphological features of senescence, increased SAbetaG expression,
      reduced proliferation, and premature senescence. VSMC senescence was mediated by
      changes in cyclins D/E, p16, p21, and pRB, and plaque VSMCs could reenter the
      cell cycle by hyperphosphorylating pRB. Both plaque and normal VSMCs expressed
      low levels of telomerase. However, telomerase expression alone rescued plaque
      VSMC senescence despite short telomeres, normalizing the cdki/pRB changes. In
      vivo, plaque VSMCs exhibited oxidative DNA damage, suggesting that telomere
      damage may be induced by oxidant stress. Furthermore, oxidants induced premature
      senescence in vitro, with accelerated telomere shortening and reduced telomerase
      activity. We conclude that human atherosclerosis is characterized by senescence
      of VSMCs, accelerated by oxidative stress-induced DNA damage, inhibition of
      telomerase and marked telomere shortening. Prevention of cellular senescence may
      be a novel therapeutic target in atherosclerosis.

PMID- 16794189
TI  - Identification of sokotrasterol sulfate as a novel proangiogenic steroid.
AB  - The potential to promote neovascularization in ischemic tissues using exogenous
      agents has become an exciting area of therapeutics. In an attempt to identify
      novel small molecules with angiogenesis promoting activity, we screened a library
      of natural products and identified a sulfated steroid, sokotrasterol sulfate,
      that induces angiogenesis in vitro and in vivo. We show that sokotrasterol
      sulfate promotes endothelial sprouting in vitro, new blood vessel formation on
      the chick chorioallantoic membrane, and accelerates angiogenesis and reperfusion
      in a mouse hindlimb ischemia model. We demonstrate that sulfation of the steroid
      is critical for promoting angiogenesis, as the desulfated steroid exhibited no
      endothelial sprouting activity. We thus developed a chemically synthesized
      sokotrasterol sulfate analog, 2beta,3alpha,6alpha-cholestanetrisulfate, that
      demonstrated equivalent activity in the hindlimb ischemia model and resulted in
      the generation of stable vessels that persisted following cessation of therapy.
      The function of sokotrasterol sulfate was dependent on cyclooxygenase-2 activity
      and vascular endothelial growth factor induction, as inhibition of either
      cyclooxygenase-2 or vascular endothelial growth factor blocked angiogenesis.
      Surface expression of alpha(v)beta(3) integrin was also necessary for function,
      as neutralization of alpha(v)beta(3) integrin, but not beta(1) integrin, binding
      abrogated endothelial sprouting and antiapoptotic activity in response to
      sokotrasterol sulfate. Our findings indicate that sokotrasterol sulfate and its
      analogs can promote angiogenesis in vitro and in vivo and could potentially be
      used for promoting neovascularization to relieve the sequelae of vasoocclusive
      diseases.

PMID- 16794191
TI  - Vascular cell locomotion: osteopontin, NADPH oxidase, and matrix
      metalloproteinase-9.

PMID- 16794192
TI  - When hearts fail so does skeletal muscle: breaking a vicious cycle.

PMID- 16794193
TI  - The potential for the transcriptome to serve as a clinical biomarker for
      cardiovascular diseases.

PMID- 16794194
TI  - Molecular diversity of receptor operated channels in vascular smooth muscle: a
      role for heteromultimeric TRP channels?

PMID- 16794195
TI  - TRPC Channel upregulation in chronically hypoxic pulmonary arteries: the HIF-1
      bandwagon gathers steam.

PMID- 16794196
TI  - Molecular profiling improves diagnoses of rejection and infection in transplanted
      organs.
AB  - The monitoring of transplanted hearts is currently based on histological
      evaluation of endomyocardial biopsies, a method that is fairly insensitive and
      that does not always accurately discriminate between rejection and infection in
      the heart. Accurate diagnosis of rejection and infection is absolutely crucial,
      however, as the respective treatments are completely different. Using
      microarrays, we analyzed gene expression in 76 cardiac biopsies from 40 heart
      recipients undergoing rejection, no rejection, or Trypanosoma cruzi infection. We
      found a set of genes whose expression patterns were typical of acute rejection,
      and another set of genes that discriminated between rejection and T cruzi
      infection. These sets revealed acute rejection episodes up to 2 weeks earlier,
      and trypanosome infection up to 2 months earlier than did histological
      evaluation. When applied to raw data from other institutions, the 2 sets of
      predictive genes were also able to accurately pinpoint acute rejection of lung
      and kidney transplants, as well as bacterial infections in kidneys. In addition
      to their usefulness as diagnostic tools, the data suggest that there are
      similarities in the biology of the processes involved in rejection of different
      grafts and also in the tissue responses to pathogens as diverse as bacteria and
      protozoa.

PMID- 16794199
TI  - Addressing the guidelines.

PMID- 16794197
TI  - Embolic signals in unselected stroke patients: prevalence and diagnostic benefit.
AB  - BACKGROUND AND PURPOSE: The present study investigated the prevalence of cerebral
      microemboli detected by transcranial Doppler sonography in unselected stroke and
      transient ischemic attack (TIA) patients under standard clinical conditions. We
      aimed to evaluate the feasibility and the value of the method for clinical use.
      METHODS: The records of 937 consecutive patients who were investigated between
      October 1995 and August 2004 at our institution were reviewed. Stroke or TIA were
      subtyped using the TOAST classification criteria. RESULTS: Two hundred and eighty
      four subjects were excluded because there was an interval of >14 days between
      onset of symptoms and examination, no definite diagnosis of stroke or TIA at
      discharge, or an artificial heart valve. Embolic signals (ES) were detected in 37
      (5.7%) of the remaining 653 patients. In subjects with positive ES detection the
      mean interval between symptom onset and ES detection was 4.9 (SD 4.0) days
      compared with 5.4 (SD 3.5) days in the remaining patients (P=0.01). ES were more
      common in patients with large-artery atherosclerosis compared with other subtype
      groups (P<0.001). The proportion of detected signals was influenced by the
      antihemostatic treatment: ES were found more often in anticoagulated patients
      than in patients receiving antiplatelet medication (P<0.001). CONCLUSIONS: The
      study shows a high clinical significance of ES in patients with recent stroke
      attributable to arterio-arterial embolism or of cardiac embolic origin and the
      high specificity of the technique. Given the low sensitivity shown, ES detection
      cannot generally be recommended for routine diagnostics in stroke patients.

PMID- 16794200
TI  - Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy
      volunteers.
AB  - BACKGROUND AND PURPOSE: Aspirin resistance may be relatively common and
      associated with adverse outcome. Meta-analysis has clearly shown that 75 mg plain
      aspirin is the lowest effective dose; however, it is not known whether the recent
      increased use of enteric-coated aspirin could account for aspirin resistance.
      This study was designed to determine whether enteric-coated aspirin is as
      effective as plain aspirin in healthy volunteers. METHODS: Seventy-one healthy
      volunteers were enrolled in 3 separate bioequivalence studies. Using a crossover
      design, each volunteer took 2 different aspirin preparations. Five aspirin
      preparations were evaluated, 3 different enteric-coated 75-mg aspirins,
      dispersible aspirin 75 mg and asasantin (25-mg standard release aspirin plus 200
      mg modified-release dipyridamole given twice daily). Serum thromboxane (TX) B2
      levels and arachidonic acid-induced platelet aggregation were measured before and
      after 14 days of treatment. RESULTS: All other aspirin preparations tested were
      inferior to dispersible aspirin (P<0.001) in their effect on serum TXB(2) level.
      Treatment failure (<95% inhibition serum TXB2 formation) occurred in 14 subjects,
      none of whom were taking dispersible aspirin. Mean weight for those demonstrating
      treatment failure was greater than those with complete TXB2 (>99%) inhibition
      (P<0.001). Using logistic regression analysis an 80-kg subject had a 20%
      probability of treatment failure. Asasantin was the most potent preparation in
      terms of inhibition of platelet aggregation. CONCLUSIONS: Equivalent doses of the
      enteric-coated aspirin were not as effective as plain aspirin. Lower
      bioavailability of these preparations and poor absorption from the higher pH
      environment of the small intestine may result in inadequate platelet inhibition,
      particularly in heavier subjects.

PMID- 16794203
TI  - Cerebral microembolism during cardiac catheterization and risk of acute brain
      injury: a prospective diffusion-weighted magnetic resonance imaging study.
AB  - BACKGROUND AND PURPOSE: Cerebral microembolism detected by transcranial Doppler
      occurs systematically during cardiac catheterization, but its clinical relevance
      remains unknown. Studies suggest that asymptomatic embolic cerebral infarction
      detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac
      interventions, especially after retrograde catheterization of the aortic valve in
      patients with valvular aortic stenosis, with a frequency as high as 22% of cases.
      We investigated the incidence of new ischemic lesions on serial cerebral DW MRI
      after cardiac catheterization. METHODS: This prospective study involved 46
      patients with severe aortic valve stenosis. To assess the occurrence of cerebral
      infarction, all patients underwent cerebral DW MRI and neurological assessment
      within 24 hours before and 48 hours after cardiac catheterization and retrograde
      catheterization of the aortic valve. A subgroup was monitored by transcranial
      power M-mode Doppler during cardiac catheterization to observe cerebral blood
      flow and track emboli. RESULTS: One patient had a focal diffusion abnormality on
      DW MRI before cardiac catheterization. After catheterization, we detected only 1
      additional acute cerebral diffusion abnormality in a single case (2.2%), although
      cerebral microemboli were detected in all transcranial Doppler-monitored patients
      during cardiac catheterization, as expected. All patients remained asymptomatic.
      Based on these results a mid-point incidence of 5.9% (95% CI, 0.01 to 12.5) for
      abnormalities on DW MRI in asymptomatic cardiac catheterization patients in our
      center can be assigned. CONCLUSIONS: Unsuspected cerebral infarctions can be
      detected by DW MRI after cardiac catheterization, but this phenomenon remains
      unfrequent in our series. Further studies are needed to identify factors
      explaining the discrepancy between these results and those of previous studies.

PMID- 16794204
TI  - Factors associated with geographic variations in stroke incidence among older
      populations in four US communities.
AB  - BACKGROUND AND PURPOSE: In the Cardiovascular Health Study (CHS), we previously
      observed lower stroke incidence in Allegheny County, PA compared with the other 3
      study sites. The purpose of this study was to study possible reasons for the
      lower stroke incidence in Allegheny County. METHODS: CHS participants 65 years or
      older who were stroke-free at baseline (n=5639) were followed between 1989 to
      1990 and 2000 for the development of stroke. Risk factors at baseline and their
      subsequent control were compared among both groups. Site-specific hazard ratios
      for stroke incidence were calculated using Cox regression models. RESULTS: The
      unadjusted hazard ratio for total stroke incidence in Forsyth County, NC;
      Sacramento County, CA; and Washington County, MD combined compared with Allegheny
      County, PA was 1.74 (95% CI: 1.42, 2.14). After adjustment for age and other
      traditional risk factors, there was modest reduction of the excess hazard in non
      Allegheny sites compared with Allegheny County (hazard ratio=1.52, 95% CI: 1.17,
      1.98). Between baseline and the seventh-year visits, control of hypertension,
      diabetes, lipids, smoking, atrial fibrillation and transient ischemic attack were
      similar across sites. White matter grade > or = 3 on the baseline brain MRI was
      less common in Allegheny County (25.8% versus 36.3%, respectively; P<0.001) and
      accounted for 25% of the excess hazard in non-Allegheny sites compared with
      Allegheny County. CONCLUSIONS: Site differences in stroke risk factors at
      baseline and subsequent control only partially explain site differences in stroke
      incidence. White matter grade as a possible integrated measure of exposure and
      control of risk factors may help in explaining geographic variations in stroke
      incidence.

PMID- 16794205
TI  - Geographic variations in stroke incidence and mortality among older populations
      in four US communities.
AB  - BACKGROUND AND PURPOSE: Stroke is a leading cause of death and disability in the
      US. There is limited data on geographic variations in stroke incidence among
      older US populations who experience the majority of stroke burden. The purpose of
      this study was to compare stroke incidence and mortality rates in 4 US
      communities. METHODS: Participants in the Cardiovascular Health Study (CHS) who
      had no history of stroke at baseline (n=5639) were followed for 10 or 7 years in
      predominantly white (n=5002) and black (n=637) participants, respectively.
      Incident stroke was validated by a stroke adjudication committee after
      ascertainment at annual visits, interim telephone contacts, and review of
      Medicare hospitalization data. RESULTS: The 2000 US population age and sex
      standardized total stroke incidence rate for all CHS participants was 17.7 per
      1000 person-years (95% CI: 15.9, 19.5). The rate was significantly lower in
      Allegheny County, Pennsylvania 9.6/1000 person-years (95% CI: 7.7, 11.5) than
      Forsyth County, North Carolina 19.2/1000 person-years (95% CI: 15.6, 22.8),
      Sacramento County, California 20.7/1000 person-years (95% CI: 16.9, 24.5), and
      Washington County, Maryland 19.8/1000 person-years (95% CI: 16.1, 23.5). The
      lower stroke incidence rate in Allegheny County was consistent in gender, race,
      and age groups. Though not statistically significant, stroke mortality was also
      lower in Allegheny County than other 3 sites. The 1-month case fatality rate was
      similar in the 4 sites for all strokes, and by stroke types. CONCLUSIONS:
      Understanding geographic variations in stroke incidence may be an important step
      in improving preventive practices of stroke.

PMID- 16794206
TI  - Frequency, management, and predictors of abnormal mood after stroke: the Auckland
      Regional Community Stroke (ARCOS) study, 2002 to 2003.
AB  - BACKGROUND AND PURPOSE: Mood disorders are an important consequence of stroke. We
      aimed to identify significant, clinically useful predictors of abnormal mood
      after stroke. METHODS: The Auckland Regional Community Stroke (ARCOS) study was a
      prospective population-based stroke incidence study conducted in Auckland, New
      Zealand, over a 12-month period from 2002 to 2003. All patients were followed up
      6 months after stroke onset and abnormal mood was assessed using the 28-item
      General Health Questionnaire (GHQ-28) administered as part of a structured
      telephone interview. Multivariate stepwise logistic regression was used to
      develop a predictive model for "caseness" (score of > or = 5 on the GHQ-28) based
      on several premorbid patient and clinical variables assessed at baseline and 28
      days of follow up. RESULTS: Of patients available at 6 months (n=1172), complete
      data on mood was available from 739 (60%) patients and 27% (95% confidence
      interval, 24 to 30%) were defined as cases. Key baseline predictors of abnormal
      mood were disability and history of depression after adjustment for sex, age, and
      comorbidity, but the model failed to predict a large amount of the variation in
      caseness (C statistic 0.587). CONCLUSIONS: This study emphasizes the complex
      nature of mood disturbance after stroke and that multiple factors are likely to
      contribute to mood disorders. A simple, clinically applicable, predictive model
      in stroke care appears difficult to develop.

PMID- 16794207
TI  - Poststroke survival for black-Caribbean populations in barbados and South london.
AB  - BACKGROUND AND PURPOSE: There are variations in mortality rates for stroke in
      black communities, but the factors associated with survival remain unclear.
      METHODS: The authors studied population-based stroke registers with follow up in
      South London (270 participants, 1995 to 2002) and Barbados (578 participants,
      2001 to 2003). Differences in sociodemographic factors, stroke risk factors and
      their management, case severity, and acute management between London and Barbados
      were studied. Survival analysis used Kaplan-Meier curves, log-rank test, and Cox
      proportional hazards model with stratification. RESULTS: There were 1411 person
      years of follow-up. Patients in Barbados had poorer survival (log-rank test
      P=0.037), particularly those with a prestroke Barthel index scores between 15 and
      20 (1-year survival, 56.4% versus 74.3%; P<0.001). This disadvantage remained
      significant (hazard ratio [HR], 1.99; 95% CI, 1.23 to 3.21, P=0.005) after
      adjustment for age and year of stroke and stratification for stroke subtype and
      socioeconomic status (SES). After stratification by SES, clinical stroke subtype,
      and Glasgow Coma Score, and adjustment for other potential confounders,
      additional factors reducing survival were untreated atrial fibrillation (AF; HR,
      8.54; 95% CI, 2.14 to 34.08, P=0.002), incontinence after stroke (HR, 2.64; 95%
      CI, 1.79 to 3.89), and dysphagia (HR, 2.25; 95% CI, 1.57 to 3.24). Patients not
      admitted to the hospital had improved survival (HR, 0.35; 95% CI, 0.21 to 0.58).
      Interaction terms between location and Barthel score, location and AF, and
      location and transient ischemic attack were included in the final model to
      reflect the greater difference in survival with a high Barthel score of 15 or
      more, absence of untreated AF, and having untreated transient ischemic attack.
      CONCLUSIONS: Black-Caribbean people with stroke living in Barbados have worse
      survival than similar patients in South London, particularly if they have good
      mobility before the stroke. Further exploration and refinement of measurement of
      confounding factors such as SES and poststroke management along with exploring
      the cultural/environmental differences between the communities is required to
      understand these stark differences.

PMID- 16794208
TI  - Estimation of the risk of stroke in black populations in Barbados and South
      London.
AB  - BACKGROUND AND PURPOSE: The incidence of stroke in black populations is a public
      health issue, but how risk varies between black communities is unclear. METHODS:
      Population-based registers in South London (SLSR) and Barbados (Barbados Register
      of Strokes [BROS]). Stroke incidence estimated by age group, gender and stroke
      subtype from January 1995 to December 2002 (SLSR), and October 2001 to September
      2003 (BROS). Incidence rate ratios [IRR] estimated adjusting for age and sex.
      RESULTS: Two hundred and seventy-one cases registered in SLSR and 628 cases in
      BROS. Average age of stroke was 66.1 years (SD 13.7) in SLSR and 71.5 years (SD
      14.9) in BROS (P<0.001). The incidence rate/1000 population in SLSR was 1.61
      (European adjusted; 95% CI, 1.41 to 1.81) and 1.08 (world adjusted; 95% CI, 0.95
      to 1.21). For Barbados incidence rates were 1.29 (European adjusted; 95% CI, 1.19
      to1.39) and 0.85 (world adjusted; 95% CI, 0.78 to 0.92). Overall IRR for SLSR:
      BROS adjusted for age and sex was 1.26 (95% CI, 1.09 to 1.46). Statistically
      significant subtype differences included total anterior cerebral infarction (IRR,
      1.82; 95% CI, 1.23 to 2.69), posterior cerebral infarction (IRR, 2.12; 95% CI,
      1.28 to 3.53), primary intracerebral hemorrhage (IRR, 1.56; 95% CI, 1.03 to 2.35)
      and subarachnoid hemorrhage (IRR, 5.04; 95% CI, 2.54 to 9.97). CONCLUSIONS: The
      risk of stroke in black Caribbeans is higher in South London than Barbados, and
      particularly so for specific stroke subtypes. The risk in Barbados approaches
      that in the white population in South London and strokes occur at an older age.
      Whether environmental factors mediate these differences in migrant populations
      requires further study.

PMID- 16794209
TI  - Analysis of thrombi retrieved from cerebral arteries of patients with acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Information regarding the histological structure of
      thromboemboli that cause acute stroke provides insight into pathogenesis and
      clinical management. METHODS: This report describes the histological analysis of
      thromboemboli retrieved by endovascular mechanical extraction from the middle
      cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with
      acute ischemic stroke. RESULTS: The large majority (75%) of thromboemboli shared
      architectural features of random fibrin:platelet deposits interspersed with
      linear collections of nucleated cells (monocytes and neutrophils) and confined
      erythrocyte-rich regions. This histology was prevalent with both cardioembolic
      and atherosclerotic sources of embolism. "Red" clots composed uniquely of
      erythrocytes were uncommon and observed only with incomplete extractions, and
      cholesterol crystals were notably absent. The histology of thromboemboli that
      could not be retrieved from 29 concurrent patients may be different. No thrombus
      >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was
      removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a
      small atheroma and attached intima were removed without clinical consequence from
      another. CONCLUSIONS: Thromboemboli retrieved from the MCA or intracranial ICA of
      patients with acute ischemic stroke have similar histological components, whether
      derived from cardiac or arterial sources. Embolus size determines ultimate
      destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The
      fibrin:platelet pattern that dominates thromboembolic structure provides a
      foundation for both antiplatelet and anticoagulant treatment strategies in stroke
      prevention.

PMID- 16794210
TI  - Intravenous recombinant tissue plasminogen activator in a pregnant woman with
      cardioembolic stroke.
AB  - BACKGROUND AND PURPOSE: Historically, the use of tissue plasminogen activator
      (tPA) thrombolysis in pregnancy has been regarded as relatively contraindicated.
      Underlying this stance has been the concern over the risk of bleeding
      complications in both mother and child. SUMMARY OF CASE: We report the successful
      use of intravenous recombinant tPA (rtPA) thrombolysis in a pregnant woman with
      acute cardioembolic stroke. CONCLUSIONS: The patient improved clinically, did not
      develop complications after receiving rtPA, and at 37 weeks' gestation, delivered
      a healthy infant, demonstrating that rtPA thrombolysis may be used safely in
      pregnant women.

PMID- 16794211
TI  - Bilateral level of effort of the plantar flexors, hip flexors, and extensors
      during gait in hemiparetic and healthy individuals.
AB  - BACKGROUND AND PURPOSE: Muscle weakness is recognized as a key factor in gait
      performance of poststroke individuals, but its impact on lower-limb muscular
      effort has been scarcely studied. The aims of this study were to compare the
      level of effort of the lower limbs of hemiparetic and able-bodied individuals and
      to assess the effect of side, cadence, and muscle group. METHODS: Seventeen
      chronic hemiparetic participants (7 females and 10 males) with a mean age of
      60.5+/-13.4 years were assessed when walking. They were compared with a group of
      14 able-bodied individuals. The level of effort was estimated from the muscular
      utilization ratio (MUR), which relates the walking moment of a given muscle group
      to its maximal potential moment. Peak MUR and MUR(area) were used as main outcome
      measures. RESULTS: Hemiparetic individuals showed greater peak MUR values (45% to
      78%) than the able-bodied subjects matched for cadence (24% to 63%). For both
      groups, the peak MUR values were similar between sides and increased with
      cadence. At self-selected cadence, the plantar flexors showed greater peak MUR
      values, whereas at maximal cadence, levels of effort for all muscles were
      equivalent. The MUR(area) values at the hip joint were greater for the
      hemiparetic group, and both groups had values that increased with cadence.
      Differences between sides and muscle groups were noted for the hemiparetic and
      healthy individuals, respectively. Large peak MUR values were associated with
      high MUR(area) values. CONCLUSIONS: For a similar cadence, the levels of effort
      of hemiparetic individuals were greater than those of the able-bodied. In the
      presence of muscle weakness, similar bilateral levels of effort could mean that
      hemiparetic individuals relied on their sense of effort while walking.

PMID- 16794213
TI  - Neurological outcome of septic cardioembolic stroke after infective endocarditis.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate mortality and
      neurological outcomes of cardioembolic cerebral stroke in infective endocarditis
      (IE) patients requiring cardiac surgery. METHODS: A consecutive series of 214
      patients undergoing cardiac surgery for IE was followed up for 20 years. In 65
      patients (mean age, 52 years), IE was complicated by computed tomography- or
      magnetic resonance imaging-verified stroke (n=61) or transient ischemic attack
      (n=4). Perioperative (30-day) and long-term mortality was assessed with
      regression models adjusting for age. Complete neurological recovery of IE
      survivors was defined by a modified Rankin score of < or = 1 and a Barthel index
      of 20 points. RESULTS: Fifty of 61 stroke patients (81.9%) survived surgery. In
      comparison with nonstroke patients, the age-adjusted perioperative mortality risk
      was 1.70-fold (95% CI, 0.73 to 3.96, P=0.22) higher and long-term mortality risk
      was 1.23-fold (95% CI, 0.72 to 2.11, P=0.45) higher in stroke patients. Patients
      with complicated stroke (meningitis, hemorrhage, or brain abscess) showed a
      higher perioperative mortality rate (38.9% vs 8.5%, P=0.007) but no higher
      neurological complication rate than patients with uncomplicated ischemic stroke.
      Complete neurological recovery was achieved in 35 IE survivors (70%, 95% CI, 55%
      to 82%). However, in the case of middle cerebral artery stroke, recovery was only
      50% and was significantly lower compared with non-middle cerebral artery stroke
      (P=0.012). CONCLUSIONS: Uncomplicated IE-related stroke showed a favorable
      prognosis with regard to both long-term survival and neurological recovery. The
      formidable risk of secondary cerebral hemorrhage due to cardiac surgery seems to
      be much lower than previously thought.

PMID- 16794212
TI  - Neglecting the difference: does right or left matter in stroke outcome after
      thrombolysis?
AB  - BACKGROUND AND PURPOSE: Patients with right hemispheric strokes (RHSs) present
      later to an emergency department, have a lower chance to receive intravenous
      recombinant tissue plasminogen activator (IV rt-PA), and have worse clinical
      outcomes than do patients with left hemispheric strokes (LHSs). We analyzed
      outcomes after IV rt-PA with respect to the side of the affected hemisphere.
      METHODS: A prospective cohort of acute stroke patients was treated with IV rt-PA
      at the London Health Sciences Centre (December 1998 to March 2003). Differences
      between patients with RHS and LHS were identified by univariate analysis.
      Logistic-regression analysis was used to determine a subset of variables
      independently associated with major neurological improvement at 24 hours and good
      outcome at 3 months after treatment. RESULTS: Of 219 stroke patients who received
      IV rt-PA, 165 had hemispheric strokes (68 RHSs and 97 LHSs). Patients with RHSs
      were less hypertensive (P=0.001) and had lower pretreatment National Institutes
      of Health Stroke Scale (NIHSS) scores (P=0.005). LHS (odds ratio [OR], 2.29; 95%
      CI, 1.14 to 4.59; P=0.019), age (OR, 0.96; 95% CI, 0.93 to 0.99; P=0.012), and
      pretreatment NIHSS (OR, 0.83; 95% CI, 0.78 to 0.89; P<0.0001) were independent
      predictors of 3-month outcome. Female sex (OR, 3; 95% CI, 1.53 to 5.90; P=0.001)
      and LHS (OR, 2.07; 95% CI, 1.05 to 4.08; P=0.03) were independent predictors of
      major neurological improvement at 24 hours after IV rt-PA. CONCLUSIONS: Despite
      higher pretreatment NIHSS, patients with LHSs have a 2-fold increased chance of a
      good outcome 3 months after rt-PA treatment compared with patients with RHSs.
      This gain can be clinically detected at 24 hours after treatment. These results
      need to be coupled with neuroimaging and hemodynamic characteristics known to
      influence stroke outcome.

PMID- 16794214
TI  - Validation study of the Siriraj Stroke score in African Nigerians and evaluation
      of the discriminant values of its parameters: a preliminary prospective CT scan
      study.
AB  - BACKGROUND AND PURPOSE: CT scanning is important to identify stroke pathology and
      exclude mimics. Its poor availability in our environment makes the search for
      simple, reliable clinical-score imperative. This study aims to validate the
      Siriraj Stroke score (SSS) and determine the discriminant values of its
      parameters in the black population of African-Nigerians. METHODS: A prospective
      multicenter study was carried out on patients that presented with stroke and had
      brain CT scan done within 14 days of onset. An interviewer structured
      questionnaire was administered and SSS computed. The stroke-type was classified
      and compared with CT diagnosis. Data were analyzed using Epi-info-2002. RESULTS:
      1122 patients presented with clinical features of stroke, of which only 101 (9%)
      could afford the cost of CT scan. Of these, 90 had CT-scan features consistent
      with acute stroke, 5 had cortical atrophy and 1 was normal. Thus, 96 patients
      were analyzed, of which 68 (71%) had cerebral ischemia and 28 (29%) had
      intracerebral hemorrhage. The 6 patients with no visible infarct on CT were
      regarded as cerebral infarction. The correlation between SSS, headache, vomiting,
      loss-of-consciousness and CT diagnosis achieved statistical significance, whereas
      atheroma markers and diastolic blood pressure did not. The SSS has an overall
      predictive accuracy of 80%. CONCLUSIONS: This preliminary study has shown that
      only 9% of our hospital stroke population had benefit of CT scan. The limited
      number of patients studied and their potential lack of representativeness,
      represent a funding issue to properly establish the performance of clinical
      scoring systems and assist in descriptive epidemiology of hospital and community
      based stroke studies in resource-poor settings. However, in this study, the SSS
      diagnosis correlates significantly with CT diagnosis.

PMID- 16794216
TI  - Lack of evidence for an association between hemodynamic variables and hematoma
      growth in spontaneous intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Early hematoma expansion in spontaneous intracerebral
      hemorrhage (ICH) is associated with worse clinical outcome. We hypothesized that
      hemodynamic parameters are associated with the increase in hematoma volume owing
      to their relationship to blood vessel wall stresses. METHODS: We performed a post
      hoc analysis of clinical and computed tomography (CT) data from patients enrolled
      in a prospective observational study of ICH patients presenting within 3 hours
      from symptom onset. Hematoma volumes were measured at hospital arrival and at 1
      and 20 hours from presentation. Blood pressure and heart rate, recorded at 19
      time points between presentation and 20 hours, were used to derive hemodynamic
      variables. Multivariable logistic-regression models were constructed to assess
      the relation between hemodynamic parameters and hematoma growth, adjusted for
      clinical covariates. RESULTS: From the original study, 98 patients underwent
      baseline and 1-hour CT scans; of these, 65 had 20-hour CT scans. Substantial
      hematoma growth was observed in 28% within the first hour. Of the 65 patients not
      undergoing surgery within 20 hours, 37% experienced hematoma growth by 20 hours.
      Neither baseline or peak hemodynamic parameters nor changes in hemodynamic
      parameters were significantly associated with hematoma growth at either 1 or 20
      hours. CONCLUSIONS: We found no blood pressure or heart rate parameters,
      individually or in combination, that were associated with hematoma growth. Our
      data suggest the influence of hemodynamic parameters on vessel wall stress to be
      an unlikely target for intervention in reducing the risk of early hematoma growth
      in ICH.

PMID- 16794215
TI  - Akt/GSK3beta survival signaling is involved in acute brain injury after
      subarachnoid hemorrhage in rats.
AB  - BACKGROUND AND PURPOSE: Apoptotic cell death is associated with acute brain
      injury after subarachnoid hemorrhage (SAH). The Akt/glycogen synthase kinase
      3beta (GSK3beta) pathway plays an important role in the cell death/survival
      pathway after a variety of cell death stimuli. However, its role in acute brain
      injury after SAH remains unknown. METHODS: We used an endovascular perforation
      model of SAH in rats. Phospho-Akt and phospho-GSK3beta expression was examined by
      Western blot analysis and immunohistochemistry. Terminal deoxynucleotidyl
      transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) and
      a cell death assay were used for detection of apoptosis. We administered LY294002
      to examine the role of the Akt/GSK3beta pathway in the phosphoinositide 3-kinase
      pathway after SAH. RESULTS: Phosphorylation of Akt and GSK3beta was accelerated
      after SAH. In the cerebral cortex, where acute brain injury was the most severe,
      phosphorylation of these proteins was observed in the early phase after SAH.
      Cortical neurons with continuous Akt phosphorylation did not colocalize with
      TUNEL-positive cells at 24 hours. LY294002 reduced Akt and GSK3beta
      phosphorylation and increased brain injury after SAH. CONCLUSIONS: The present
      study suggests that the Akt/GSK3beta pathway might be involved in neuronal
      survival in acute brain injury after SAH.

PMID- 16794217
TI  - Central compensation at short muscle range is differentially affected in cortical
      versus subcortical strokes.
AB  - BACKGROUND AND PURPOSE: The active force generated by a single muscle fiber is
      greatest in midrange. In healthy subjects, the reduced muscle force at short
      muscle length is partially compensated by modified patterns of muscle activation,
      probably central in origin. These patterns are presumed to be deficient after
      stroke. We examined the excitability muscle-length relation in stroke patients
      and healthy controls and hypothesized about its alteration in stroke patients.
      METHODS: Corticospinal excitability was assessed in 31 stroke patients (19
      subcortical, 12 cortical) and 19 healthy volunteers by transcranial magnetic
      stimulation. We recorded the motor evoked potentials (MEPs) simultaneously from
      the biceps brachii and the triceps brachii muscles at 0 degrees, 20 degrees, 40
      degrees, 60 degrees, 80 degrees, 100 degrees, and 120 degrees degrees of elbow
      flexion (0 degrees being full elbow extension). RESULTS: Normal subjects revealed
      a significant increase in MEP amplitudes at shortened muscle lengths for both the
      flexor and extensor muscles (P<0.001). Multivariate variance analysis revealed
      that the MEP-angle curves of cortical stroke patients were significantly
      different from those of the control group for both muscles, lacking an increase
      of corticospinal excitability at short muscle length. Yet the MEP-angle curves
      for the subcortical stroke patients did not show a statistically significant
      difference from the control group for either muscle. CONCLUSIONS: Cortical and
      subcortical strokes differentially affect the corticospinal excitability muscle
      length relation. This may account for the reported disproportionate decrease in
      muscle strength at shortened range after stroke.

PMID- 16794218
TI  - Angiogenesis in atherogenesis.
AB  - Atherogenesis is the pathobiological process, which underlies atherosclerotic
      cardiovascular disease and evolves in the 3 stages of initiation, progression,
      and complication to clinical significance. Of note, this process is associated
      with neovascularization, and it was not until recently that the implications of
      angiogenesis in atherogenesis were delineated. This article gives an updated
      overview on this topic and briefly reflects on the similarities with neovessel
      formation in carcinogenesis.

PMID- 16794219
TI  - The changing roles of dietary carbohydrates: from simple to complex.
AB  - The dietary recommendations made for carbohydrate intake by many
      organizations/agencies have changed over time. Early recommendations were based
      on the need to ensure dietary sufficiency and focused on meeting micronutrient
      intake requirements. Because carbohydrate-containing foods are a rich source of
      micronutrients, starches, grains, fruits, and vegetables became the foundation of
      dietary guidance, including the base of the US Department of Agriculture's Food
      Guide Pyramid. Dietary sufficiency recommendations were followed by
      recommendations to reduce cholesterol levels and the risk for cardiovascular
      disease; reduction in total fat (and hence saturated fat) predominated. Beginning
      in the 1970s, carbohydrates were recommended as the preferred substitute for fat
      by the American Heart Association and others to achieve the recommended
      successive reductions in total fat and low-density lipoprotein cholesterol (LDL
      C). Additional research on fats and fatty acids found that monounsaturated fatty
      acids could serve as an alternative substitution for saturated fats, providing
      equivalent lowering of LDL-C without concomitant reductions in high-density
      lipoprotein cholesterol and increases in triglycerides witnessed when
      carbohydrates replace saturated fat. This research led to a sharper focus in the
      guidelines in the 1990s toward restricting saturated fat and liberalizing a range
      of intake of total fat. Higher-fat diets, still low in saturated fatty acids,
      became alternative strategies to lower-fat diets. As the population has become
      increasingly overweight and obese, the emergence of the metabolic syndrome and
      its associated disruptions in glucose and lipid metabolism has led to
      reconsiderations of the role of carbohydrate-containing foods in the American
      diet. Consequently, a review of the evidence for and against high-carbohydrate
      diets is important to put this controversy into perspective. The current dietary
      recommendations for carbohydrate intake are supported by the evidence.

PMID- 16794220
TI  - Establishment of a functionally active collagen-binding vascular endothelial
      growth factor fusion protein in situ.
AB  - OBJECTIVE: Tissue regeneration requires both growth factor and extracellular
      matrix such as collagen, serving as a scaffold for cell growth. We established
      FNCBD-VEGF121, consisting of the fibronectin collagen-binding domain (FNCBD) and
      vascular endothelial growth factor (VEGF) 121, and investigated its properties.
      METHODS AND RESULTS: FNCBD-VEGF121 specifically bound to gelatin and type I, II,
      III, IV, and V collagen. This collagen-bound FNCBD-VEGF121 captured soluble VEGF
      receptor 2 (VEGFR-2)/Fc chimeric protein. Cell growth-promoting activity of FNCBD
      VEGF121 was almost identical to that of VEGF121. The VEGF fusion protein
      significantly enhanced the expression of VEGFR-2 (71.6+/-0.8%) on endothelial
      progenitor cells (EPCs) derived from umbilical cord blood. Expectably, the
      collagen-bound VEGF fusion protein not only promoted the growth of endothelial
      cells (ECs) but also induced the expression of VEGFR-2 (63.7+/-0.8%) on non
      adherent cells expanded from bone marrow CD34+ cells. Moreover, the VEGF fusion
      protein enhanced sprout formation of ECs in a matrigel model. In vivo experiments
      revealed that FNCBD-VEGF121 had local effects but not systemic effect on EPC
      mobilization. CONCLUSIONS: These results suggest that FNCBD-VEGF121 stably
      maintains an optimally high and local concentration of VEGF with collagen matrix
      and stimulates both ECs and EPCs in situ, supplying a vascular regeneration
      niche.

PMID- 16794222
TI  - Chimeric VEGF-E(NZ7)/PlGF promotes angiogenesis via VEGFR-2 without significant
      enhancement of vascular permeability and inflammation.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) plays critical roles in the
      regulation of angiogenesis and lymphangiogenesis. However, tissue edema,
      hemorrhage, and inflammation occur when VEGF-A is used for angiogenic therapy. To
      design a novel angiogenic factor without severe side effects, we examined the
      biological function of chimeric VEGF-E(NZ7)/placental growth factor (PlGF), which
      is composed of Orf-Virus(NZ7)-derived VEGF-E(NZ7) and human PlGF1, in a
      transgenic (Tg) mouse model. METHODS AND RESULTS: A strong angiogenic response
      was observed in both VEGF-E(NZ7)/PlGF and VEGF-A165 Tg mice. Notably, the
      vascular leakage of VEGF-E(NZ7)/PlGF-induced blood vessels was 4-fold lower than
      that of VEGF-A165-induced blood vessels. Furthermore, the monocyte/macrophage
      recruitment in the skin of VEGF-E(NZ7)/PlGF Tg mice was approximately 8-fold
      decreased compared with that of VEGF-A165 Tg mice. In addition, the lymphatic
      vessels in VEGF-E(NZ7)/PlGF Tg mice were structurally normal, whereas they were
      markedly dilated in VEGF-A165 Tg mice, possibly because of the high vascular
      leakage. Receptor binding assay demonstrated that VEGF-E(NZ7)/PlGF was the ligand
      only activating VEGF receptor (VEGFR)-2. CONCLUSIONS: These results indicated
      that neither the hyperpermeability in response to simultaneous stimulation of
      VEGFR-1 and VEGFR-2 nor VEGFR-1-mediated severe inflammation was associated with
      VEGF-E(NZ7)/PlGF-induced angiogenesis. The unique receptor binding property may
      shed light on VEGF-E(NZ7)/PlGF as a novel candidate for therapeutic angiogenesis.

PMID- 16794221
TI  - Thyroid hormone inhibits vascular remodeling through suppression of cAMP response
      element binding protein activity.
AB  - OBJECTIVE: Although accumulating evidences suggest that impaired thyroid function
      is a risk for ischemic heart disease, the molecular mechanism of anti
      atherosclerotic effects of thyroid hormone is poorly defined. We examined whether
      thyroid hormone affects signaling pathway of angiotensin II (Ang II), which is
      critically involved in a broad aspect of cardiovascular disease process. METHODS
      AND RESULTS: 3,3',5-triiodo-L-thyronine (T3) did not show a significant effect on
      Ang II-induced activation of extracellular signal-regulated protein kinase or p38
      mitogen-activated protein kinase in vascular smooth muscle cells (VSMCs), whereas
      T3 inhibited Ang II-induced activation of cAMP response element (CRE) binding
      protein (CREB), a nuclear transcription factor involved in the vascular
      remodeling process. Coimmunoprecipitaion assay revealed the protein-protein
      interaction between thyroid hormone receptor and CREB. T3 reduced an expression
      level of interleukin (IL)-6 mRNA, CRE-dependent promoter activity, and protein
      synthesis induced by Ang II. Administration of T3 (100 microg/100 g for 14 days)
      to rats attenuated neointimal formation after balloon injury of carotid artery
      with reduced CREB activation and BrdU incorporation. CONCLUSIONS: These results
      suggested that T3 inhibits CREB/CRE signaling pathway and suppresses cytokine
      expression and VSMCs proliferation, which may account for, at least in part, an
      anti-atherosclerotic effect of thyroid hormone.

PMID- 16794223
TI  - Phosphatidylinositol-3-kinase regulates scavenger receptor class B type I
      subcellular localization and selective lipid uptake in hepatocytes.
AB  - OBJECTIVE: The high-density lipoprotein (HDL) receptor scavenger receptor Class B
      type I (SR-BI) plays a key role in mediating the final step of reverse
      cholesterol transport. This study examined the possible regulation of hepatic SR
      BI by phosphatidylinositol-3-kinase (PI3K), a well known regulator of endocytosis
      and membrane protein trafficking. METHODS AND RESULTS: SR-BI-dependent HDL
      selective cholesterol ester uptake in human HepG2 hepatoma cells was decreased
      (approximately 50%) by the PI3K inhibitors wortmannin and LY294002. Insulin
      increased selective uptake (approximately 30%), and this increase was blocked by
      PI3K inhibitors. Changes in SR-BI activity could be accounted for by pronounced
      changes in the subcellular localization and cell surface expression of SR-BI as
      determined by HDL cell surface binding, receptor biotinylation studies, and
      confocal fluorescence microscopy of HepG2 cells expressing green fluorescent
      protein-tagged SR-BI. Thus, under conditions of PI3K activation by insulin, and
      to a lesser extent by the SR-BI ligand HDL, cell surface expression of SR-BI was
      promoted, resulting in increased SR-BI-mediated HDL selective lipid uptake.
      CONCLUSIONS: Our data indicate that PI3K activation stimulates hepatic SR-BI
      function post-translationally by regulating the subcellular localization of SR-BI
      in a P13K-dependent manner. Decreased hepatocyte PI3K activity in insulin
      resistant states, such as type 2 diabetes, obesity, or metabolic syndrome, may
      impair reverse cholesterol transport by reducing cell surface expression of SR
      BI.

PMID- 16794224
TI  - Upregulation of arginase by H2O2 impairs endothelium-dependent nitric oxide
      mediated dilation of coronary arterioles.
AB  - OBJECTIVE: Overproduction of reactive oxygen species such as hydrogen peroxide
      (H2O2) has been implicated in various cardiovascular diseases. However,
      mechanism(s) underlying coronary vascular dysfunction induced by H2O2 is unclear.
      We studied the effect of H2O2 on dilation of coronary arterioles to endothelium
      dependent and endothelium-independent agonists. METHODS AND RESULTS: Porcine
      coronary arterioles were isolated and pressurized without flow for in vitro
      study. All vessels developed basal tone and dilated dose-dependently to
      activators of nitric oxide (NO) synthase (adenosine and ionomycin),
      cyclooxygenase (arachidonic acid), and cytochrome P450 monooxygenase
      (bradykinin). Intraluminal incubation of vessels with H2O2 (100 micromol/L, 60
      minutes) did not alter basal tone but inhibited vasodilations to adenosine and
      ionomycin in a manner similar as that by NO synthase inhibitor L-NAME. H2O2
      affected neither endothelium-dependent responses to arachidonic acid and
      bradykinin nor endothelium-independent dilation to sodium nitroprusside. The
      inhibited adenosine response was not reversed by removal of H2O2 but was restored
      by excess L-arginine. Inhibition of L-arginine consuming enzyme arginase by alpha
      difluoromethylornithine or N(omega)-hydroxy-nor-L-arginine also restored
      vasodilation. Administering deferoxamine, an inhibitor of hydroxyl radical
      production, prevented the H2O2-induced impairment of vasodilation to adenosine.
      Western blot and reverse-transcription polymerase chain reaction results
      indicated that arginase I was upregulated after treating vessels with H2O2.
      CONCLUSIONS: H2O2 specifically impairs endothelium-dependent NO-mediated dilation
      of coronary microvessels by reducing L-arginine availability through upregulation
      of arginase. The formation of hydroxyl radicals from H2O2 may contribute to this
      process.

PMID- 16794225
TI  - A natural antibody to oxidized cardiolipin binds to oxidized low-density
      lipoprotein, apoptotic cells, and atherosclerotic lesions.
AB  - OBJECTIVE: Cardiolipin (CL) is found in membranes of bacteria, in the inner
      membrane of mitochondria and in plasma low-density lipoprotein (LDL).
      Anticardiolipin antibodies (aCL) are associated with disease states, and we have
      suggested that many aCL bind to oxidized CL (oxCL) but not native CL. To
      determine the immunogenicity and origins of oxCL in vivo, we cloned a natural
      antibody to oxCL. METHODS AND RESULTS: A monoclonal IgM antibody to oxCL (LRO1)
      was cloned from a nonimmunized LDLR-/- mouse. The V(H) sequence originated from
      the V(H)Gam3.8 germline with one nucleotide difference, and the Vkappa was 100%
      identical to Vkappa19-20 germline gene, making LRO1 a natural antibody. LRO1
      bound specifically to oxCL and oxidized-LDL, but not to native CL or native LDL.
      LRO1 epitopes were demonstrated in apoptotic, but not in viable, Jurkat cells by
      flow cytometry, immunofluorescence and deconvolution microscopy. Human and rabbit
      atherosclerotic lesions contained LRO1 epitopes. Human LDL (n=113) showed LRO1
      immunoreactivity, which correlated with aCL IgG titers (r=0.32, P=0.0004).
      CONCLUSIONS: These data demonstrate that some aCL antibodies are highly conserved
      natural antibodies binding to oxCL in oxLDL, apoptotic cells, and atherosclerotic
      lesions. This suggests that oxCL is one of the pathogen-associated molecular
      patterns of innate immunity and gives insight into the pathogenic events of
      diseases with increased titers of aCL antibodies.

PMID- 16794227
TI  - Inhibition of extracellular signal-regulated kinase in liver of
      hyperhomocysteinemic mice.

PMID- 16794228
TI  - Modulation of toll-like receptor expression: a further effect of statins?

PMID- 16794229
TI  - Vasoocclusion in sickle cell anemia: are platelets really involved?

PMID- 16794230
TI  - Beneficial effects of neuronal nitric oxide synthase in atherosclerosis.

PMID- 16794231
TI  - New tricks from an old dog: nitric oxide-independent effects of dimethylarginine
      dimethylaminohydrolase.

PMID- 16794232
TI  - Inflammation and atherosclerosis: Group IIa and Group V sPLA2 are not redundant.

PMID- 16794234
TI  - Uses and abuses of tumor markers in the diagnosis, monitoring, and treatment of
      primary and metastatic breast cancer.
AB  - Although breast cancer incidence continues to increase, mortality has been
      decreasing, principally as a result of earlier detection and improvements in
      adjuvant systemic therapy. Nonetheless, because antineo-plastic agents are
      associated with substantial morbidity and occasional mortality, efforts to
      individualize treatment strategies are desirable. In addition to classic
      histopathologic diagnosis, molecular and cellular tumor markers may help in
      establishing prognosis or prediction of benefit. Recommendations for routine use
      of tumor markers in breast cancer have been conservative. Although several
      studies have been reported, few are of sufficiently high level of evidence to
      permit solid conclusions. Three key issues in tumor marker evaluation are
      utility, magnitude, and reliability. Poorly conceived study designs cloud the
      issue of how the marker might be used. Reliance on p-values rather than the size
      of the differences in outcome between patients who are positive and those who are
      negative for the factor obscures the importance. Technical issues result in poor
      reproducibility and interpretability of assays. Analytical issues lead to poorly
      defined cutoff values for marker levels. Poor patient selection leads to
      difficulty interpreting results because of confounders such as differences in
      treatment regimens. This review focuses on these issues, with an emphasis on
      currently accepted tumor markers. Finally, new tumor marker reporting
      recommendations are discussed, the adoption of which may lead to improved design
      and publication of tumor marker studies in the future.

PMID- 16794235
TI  - Aromatase inhibitors in breast cancer: an overview.
AB  - We examined published reports on the use of aromatase inhibitors in
      postmenopausal patients with hormone receptor-positive breast cancer. Our data
      were obtained through a MEDLINE search of literature published in English.
      Current data indicate that aromatase inhibitors are equivalent or superior to
      tamoxifen as first-line therapy for metastatic breast cancer and as neoadjuvant
      treatment for primary breast cancer. In addition, randomized studies have shown
      that aromatase inhibitors can be administered instead of tamoxifen as a single
      agent for 5 years or sequentially with tamoxifen for 5 or 10 years. These choices
      should be discussed with the patient, considering the estimated risk for
      recurrence and other associated comorbid conditions such as osteoporosis and
      thromboembolism.

PMID- 16794236
TI  - Multidisciplinary therapy of locally far-advanced or inflammatory breast cancer
      with fixed perioperative sequence of epirubicin, vinorelbine, and Fluorouracil
      chemotherapy, surgery, and radiotherapy: long-term results.
AB  - BACKGROUND: Based on phase II data in advanced breast cancer (BC), the
      fluorouracil, epirubicin, and vinorelbine (FEN) combination was assessed as
      perioperative chemotherapy, integrated in a multidisciplinary treatment for
      locally advanced BC. PATIENTS AND METHODS: Patients with newly diagnosed
      inoperable (stage IIIB or inflammatory) BC. Multimodality treatment protocol
      consisted of four preoperative courses of fluorouracil (600 mg/m(2) day 1),
      epirubicin (75 mg/m(2) day 1), and vinorelbine (25 mg/m(2) day1 and day 8), all
      i.v. every 21 days, followed by radical or conservative surgery according to
      clinical response and four postoperative identical chemotherapy courses aimed to
      eradicate micrometastatic disease. Locoregional radiotherapy was offered to all
      patients after the completion of chemotherapy followed by hormonotherapy
      according to hormone receptor status. The primary end points of the study were:
      (a) clinical and pathological response, (b) downstaging and conversion to
      operable disease, and (c) recurrence-free survival (RFS) and overall survival
      (OS). RESULTS: Forty-eight women, one stage IIIA, 27 (56.2%) stage IIIB, two
      stage IIIC (4.1%), and 12 (25%) with inflammatory BC, aged 34-75 years (median,
      52), were accrued. Thirty-eight and 34 patients completed the planned pre- and
      postoperative chemotherapy, respectively. Totals of 175 and 135 cycles were
      administered pre- and postoperatively, respectively. Toxicity of both phases,
      mainly hematologic, was in general acceptable without treatment-related death.
      Venous reactions were a frequent problem. All but three tumors were converted to
      operable, 31.3% with breast conservation. The clinical response rate (RR) was
      77.7% (22.2% complete) and pathological RR was 73.3% (complete, 20% in both
      primary and axilla). After a median follow-up of 72 months, 62.5% and 16.7% of
      patients remain relapse free at 3 and 5 years, respectively, while 83% and 58.3%
      were alive 3 and 5 years, respectively, after the start of chemotherapy. Median
      RFS and OS have not yet been reached, and are currently 37+ and 62+ months,
      respectively. CONCLUSION: This fixed number of FEN perioperative courses schedule
      followed by radiotherapy is safe and highly active in inducing both local and
      distant control of locally far-advanced BC. This strategy is at least not
      inferior to other established regimens or strategies for locally far-advanced BC,
      while the integration of taxanes or new targeted agents may help show its true
      value for this challenging clinical entity.

PMID- 16794237
TI  - Primary systemic therapy of breast cancer.
AB  - Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic
      breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a
      complete pathological response (pCR), and reduce the extent of surgery. The
      multitude of clinical trials using PST in breast cancer patients has not proven
      the fundamental hypotheses of improved overall survival and disease-free survival
      that drove the investigation of PST. The other potential advantages of PST, which
      include increasing the rate of breast-conserving surgery and predicting outcome
      to a particular chemotherapy regimen, are also not conclusively established. We
      examined the published literature on PST for breast cancer and predominantly
      focused our review on data from large, randomized clinical trials comparing
      primary systemic chemotherapy with adjuvant chemotherapy, different primary
      systemic chemotherapy regimens, primary systemic chemotherapy with hormonal
      therapy, and different preoperative hormonal therapies. Although the optimal
      neoadjuvant chemotherapy regimen has not been established, a combination of four
      cycles of an anthracycline followed by four cycles of a taxane appears to produce
      the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer,
      concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane
      combination has produced provocative results that require further confirmatory
      studies. Preoperative hormonal therapy is associated with low pCR rates and
      should be reserved for patients who are poor candidates for systemic
      chemotherapy. The optimal management of patients with residual disease after the
      administration of maximum neoadjuvant therapy remains to be defined. The surgical
      approach, including the role of sentinel node biopsy and delivery of radiation
      therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials
      will help identify the subset of patients who would most benefit from the use of
      PST, establish the most effective PST regimen, and determine the optimal
      multidisciplinary approach in the management of breast cancer.

PMID- 16794238
TI  - Cancer in 15- to 29-year-olds by primary site.
AB  - INCIDENCE: Cancer occurring between the ages of 15 and 30 years is 2.7 times more
      common than cancer occurring during the first 15 years of life, yet is much less
      common than cancer in older age groups, and accounts for just 2% of all invasive
      cancer. Cancer in adolescents and young adults is unique in the distribution of
      the types that occur. Hodgkin lymphoma, melanoma, testis cancer, female genital
      tract malignancies, thyroid cancer, soft-tissue sarcomas, non-Hodgkin lymphoma,
      leukemia, brain and spinal cord tumors, breast cancer, bone sarcomas, and
      nongonadal germ cell tumors account for 95% of the cancers in this age group. The
      frequency distribution of cancer types changes dramatically from age 15-30, such
      that the pattern at the youngest age does not resemble the one at the oldest. The
      incidence of cancer in this age group increased steadily during the past quarter
      century. This increase is declining and at the older end of the age range appears
      to be returning to the incidence of the 1970s. Males in the 15- to 29-year age
      group have been at higher risk of developing cancer, with the risk directly
      proportional to age. Non-Hispanic whites have had the highest risk of developing
      cancer during this phase of life, and Asians, American Indians and Native
      Alaskans the lowest. Males had a worse prognosis than females. African-Americans,
      American Indian/Alaska Natives had a worse prognosis than white non-Hispanics and
      Asians. MORTALITY & SURVIVAL: At the beginning of the last quarter century, the
      diagnosis of cancer in 15- to 29-year-olds carried a more favorable prognosis, on
      the average, relative to cancer at other ages. Since then, there has been a lack
      of progress in survival improvement among older adolescents and young adults
      relative to all other ages. Survival improvement trends portend a worse prognosis
      for young adults diagnosed with cancer today than 25 years ago. The survival
      deficit is increasing with longer follow-up of the survivors, and is worse in
      males. Among 15- to 29-year-olds, non-Hispanic whites had the best survival and
      African Americans/blacks had the worst survival, with a 20% difference apparent
      by 5 years. Asians/Pacific Islanders had the second best survival, with Hispanics
      and American Indians/Alaska Natives next in sequence. RISK FACTORS: In general,
      there are relatively scant data to support either an environmental causation or
      an inherited predisposition to cancer in this age group. The majority of cases of
      cancer occurring before age 30 appear to be spontaneous and unrelated to either
      carcinogens in the environment or family cancer syndromes. Overall, family cancer
      syndromes appear to account for less than 5% of the cases of cancer in the age
      group. Melanoma, cervical carcinoma and Kaposi sarcoma, non-Hodgkin lymphoma,
      Hodgkin and Burkitt lymphomas accounting for the majority of environmentally
      induced malignancies (ultraviolet light, human papillomavirus, human
      immunodeficiency virus, and Epstein-Barr virus, respectively). Ultimately, a
      larger proportion of cases may be attributable to specific factors or genetic
      predisposition, but at present, most cancer in this age group appears to be
      sporadic and random.

PMID- 16794240
TI  - Locally advanced pancreatic cancer: current therapeutic approach.
AB  - Even though pancreatic cancer accounts for only 2% of all cancer diagnoses in the
      U.S., it is the fourth-leading cause of cancer death and one of the most
      difficult malignancies to manage. Because of the usually late onset of symptoms,
      only 10%-15% of patients present with resectable disease, whereas the remaining
      85%-90% present with locally advanced unresectable or metastatic disease. Despite
      a lack of consistent evidence from previous clinical trials, chemotherapy in
      addition to radiation therapy is the most commonly used approach in treating
      locally advanced pancreatic cancer. The most appropriate chemotherapy in
      combination with radiation is still debatable between 5-fluorouracil and
      gemcitabine, and novel trends to prevent resistance and enhance efficacy
      incorporate biologically targeted agents. This paper reviews the current
      management options, controversies, and ongoing and future directions for the
      treatment of locally advanced adenocarcinoma of the pancreas.

PMID- 16794239
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors: present and future
      role in gastrointestinal cancer treatment: a review.
AB  - BACKGROUND: Despite advances in conventional and targeted anticancer therapy, the
      prognosis remains poor for many patients with solid tumors. Ongoing research into
      the molecular basis of malignant disease, however, has yielded many novel agents
      with potential activity, including the epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs). DESIGN: This review summarizes current clinical
      data for EGFR-TKIs as monotherapy or in combination with 5
      fluorouracil/leucovorin, irinotecan, or oxaliplatin, focusing on the rapidly
      developing area of colorectal, gastroesophageal, and pancreatic cancers. RESULTS:
      EGFR-TKIs have limited but valuable activity as monotherapy in non-small cell
      lung cancer patients who have received prior anticancer treatment. The potential
      for application as a single agent in colorectal, gastroesophageal, and pancreatic
      cancers has yet to be demonstrated conclusively and deserves further
      investigation, especially as second- or third-line therapy. In combination with
      oxaliplatin-based regimens and 5-fluorouracil/leucovorin-based regimens, TKIs
      have shown benefits, suggesting that there may be a synergistic effect with
      chemotherapy. However, combinations with irinotecan-based regimens have been
      limited by toxicities. CONCLUSIONS: EGFR-TKIs show benefits when used in
      combination with chemotherapy, and the favorable toxicity profiles observed
      suggest that these may be of value in frail or elderly patients.

PMID- 16794241
TI  - End points for adjuvant therapy trials: has the time come to accept disease-free
      survival as a surrogate end point for overall survival?
AB  - The intent of adjuvant therapy is to eradicate micro-metastatic residual disease
      following curative resection with the goal of preventing or delaying recurrence.
      The time-honored standard for demonstrating efficacy of new adjuvant therapies is
      an improvement in overall survival (OS). This typically requires phase III trials
      of large sample size with lengthy follow-up. With the intent of reducing the cost
      and time of completing such trials, there is considerable interest in developing
      alternative or surrogate end points. A surrogate end point may be employed as a
      substitute to directly assess the effects of an intervention on an already
      accepted clinical end point such as mortality. When used judiciously, surrogate
      end points can accelerate the evaluation of new therapies, resulting in the more
      timely dissemination of effective therapies to patients. The current review
      provides a perspective on the suitability and validity of disease-free survival
      (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and
      the advantages and limitations associated with the use of DFS as a primary end
      point in adjuvant clinical trials and as the basis for approval of new adjuvant
      therapies are discussed.

PMID- 16794242
TI  - The role of perioperative chemotherapy in the treatment of urothelial cancer.
AB  - Cancer of the urothelium is the fourth most common malignancy in men in the U.S.
      and the ninth most common in women. More than 63,000 Americans will be diagnosed
      with bladder cancer this year (47,010 men and 16,200 women), and more than 13,000
      (8,970 men and 4,210 women) can expect to die of their disease. The approximate
      5:1 ratio of incidence to mortality roughly parallels the frequency of
      superficial to invasive disease. Efforts to improve this ratio have generated a
      potential paradigm shift in the treatment of urothelial cancer, incorporating
      increasingly active chemotherapy into treatment regimens for high-risk tumors in
      both the pre-and postoperative settings. This review summarizes the evolution of
      chemotherapeutic treatment of urothelial cancer and the rationale for its
      perioperative administration and addresses the future directions of clinical
      research in this field.

PMID- 16794243
TI  - Symptoms and treatment in cancer therapy-induced early menopause.
AB  - Young women with breast cancer often experience early menopause as a result of
      the therapy for their malignant disease. The sudden occurrence of menopause
      resulting from chemotherapy, oophorectomy, radiation, or gonadal dysgenesis
      frequently results in hot flashes that begin at a younger age and may occur at a
      greater frequency and intensity than hot flashes associated with natural
      menopause. Hormone therapy relieves symptoms effectively in 80%-90% of women who
      initiate treatment. This therapy, however, is generally contraindicated in
      estrogen-dependent cancers, such as breast cancer, because of the potentially
      increased risk for recurrence. Many agents have been investigated as potential
      means for alleviating hot flashes in survivors of breast cancer, such as
      progestagens, clonidine, gabapentin, and anti-depressants. Several complementary
      and alternative medicines frequently used by patients have also been studied.
      These include black cohosh, phytoestrogens, homeopathy, vitamin E, acupuncture,
      and behavior strategies. To support the use of one of more of these
      nonpharmacological or pharmacological options in the treatment of hot flashes in
      breast cancer patients, more evidence from well-controlled clinical trials is
      needed. In particular, soundly based scientific research with complementary and
      alternative medicine therapies is lacking. Pharmacological treatments appear to
      be more beneficial than nonpharmacological treatments. This article reviews the
      current literature to assess the epidemiology and diagnosis of hot flashes and
      the nonpharmacological and pharmacological options for the treatment of hot
      flashes, in breast cancer patients in particular. When specific treatment options
      have not been evaluated in breast cancer patients specifically, published data on
      the management of hot flashes with this modality in healthy postmenopausal women
      are described.

PMID- 16794244
TI  - Salvage therapy for advanced non-small cell lung cancer: factors influencing
      treatment selection.
AB  - Novel chemotherapies and molecularly targeted agents have improved outcomes for
      patients with advanced non-small cell lung cancer (NSCLC). Several efficacious
      regimens are available, which allows for selection of therapy based on factors
      such as schedule, toxicity profile, patient-specific needs, and individual
      preferences of the patient. Treatment guidelines recommend platinum-based
      chemotherapy first line for patients with a good performance status. These
      regimens offer a modest survival advantage over best supportive care. The role of
      targeted biologic agents in this setting is being assessed in phase II trials.
      Results to date show promising activity and tolerability. Erlotinib, docetaxel,
      and pemetrexed are all approved for patients who progress following one prior
      regimen for advanced NSCLC. These agents have different tolerability profiles and
      routes of administration but appear to have similar effects on tumor response and
      survival, though comparative trials are required to confirm this. Based on the
      results of a phase III trial, erlotinib is also recommended for third-line use in
      patients with NSCLC. Identifying predictive markers of clinical response to
      therapy may provide an opportunity to better select patient subsets appropriate
      for specific treatment. Recent data have linked various clinical characteristics
      and biologic markers with outcome to HER-1/EGFR-targeted agents. However, many of
      these studies are retrospective and based on small patient numbers, and there is
      evidence of broad benefit across diverse patient subgroups with erlotinib.
      Prospective, randomized trials are required to validate potential predictive
      markers fully before they are applied to clinical practice.

PMID- 16794246
TI  - Post-transplant lymphoproliferative disorders.
AB  - Post-transplant lymphoproliferative disorder is the most common malignancy, with
      the exception of skin cancer, after solid organ transplantation in adults. The
      incidence varies according to the transplanted organ and is often associated with
      Epstein-Barr virus. Prognosis is variable, due in part to the heterogeneity of
      the disease, which ranges from reactive plasmacytic hyperplasia to aggressive
      monoclonal disease.

PMID- 16794245
TI  - Liposomal doxorubicin, cyclophosphamide, and etoposide and antiretroviral therapy
      for patients with AIDS-related lymphoma: a pilot study.
AB  - PURPOSE: To evaluate in a pilot study the safety and efficacy of liposomal
      doxorubicin, cyclophosphamide, and etoposide (LACE) when combined with
      antiretroviral therapy (ART) in patients with AIDS-related lymphoma (ARL). The
      impact of HIV viral control on therapy and survival was also assessed. PATIENTS
      AND METHODS: Between 1994 and 2005, 40 patients at Virginia Mason Medical Center
      were diagnosed with ARL. Twelve received LACE every 28 days. All patients
      received intrathecal chemoprophylaxis, ART, and G-CSF. RESULTS: The median
      patient CD4+ count was 190 cells/microl (range, 20-510 cells/microl), and the
      median HIV viral load (VL) was 61,613 copies/ml (range, <50-500,000 copies/ml).
      Seven patients (58%) had an International Prognostic Index score of 3 or 4. Six
      patients (50%) were ART-naive, five were viremic despite ART, and one had an
      undetectable HIV-1 VL. Nine patients (75%) achieved a complete response (CR), and
      median overall survival was 107 months. At a median follow-up of 46 months, the
      recurrence-free survival rate was 50%. Two patients died from relapsed/refractory
      ARL and one patient achieved a CR with salvage therapy. One CR patient died from
      complications of pneumonia, and another CR patient died from uncertain causes 5
      years after treatment. Grade 3 or 4 neutropenia occurred in 23 of 61 (38%)
      chemotherapy cycles. Hospitalization was required after 5% of treatment cycles
      due to neutropenic fever. CONCLUSION: LACE is an effective and tolerable
      treatment for ARL. HIV viral control can be maintained in the majority of
      patients during and after completion of LACE.

PMID- 16794247
TI  - Low-grade gliomas in adults.
AB  - Low-grade gliomas are a heterogeneous group of neoplasms usually encountered in
      younger patient populations. These tumors represent a unique challenge because
      most patients will survive a decade or more and may be at a higher risk for
      treatment-related complications. Clinical observations over the years have
      identified a subset of low-grade gliomas that tends to manifest more aggressive
      clinical behavior and require earlier, more aggressive intervention. Clinical and
      molecular parameters may allow better assessment of prognosis and application of
      risk-adjusted management strategies that may include resection, radiation, or
      chemotherapy. Improved methods of long-term cognitive and functional assessment
      are desperately needed in this patient population.

PMID- 16794248
TI  - Understanding and managing methotrexate nephrotoxicity.
AB  - Methotrexate (MTX) is one of the most widely used anti-cancer agents, and
      administration of high-dose methotrexate (HDMTX) followed by leucovorin (LV)
      rescue is an important component in the treatment of a variety of childhood and
      adult cancers. HDMTX can be safely administered to patients with normal renal
      function by the use of alkalinization, hydration, and pharmacokinetically guided
      LV rescue. Despite these measures, HDMTX-induced renal dysfunction continues to
      occur in approximately 1.8% of patients with osteosarcoma treated on clinical
      trials. Prompt recognition and treatment of MTX-induced renal dysfunction are
      essential to prevent potentially life-threatening MTX-associated toxicities,
      especially myelosuppression, mucositis, and dermatitis. In addition to
      conventional treatment approaches, dialysis-based methods have been used to
      remove MTX with limited effectiveness. More recently carboxypeptidase-G(2)
      (CPDG(2)), a recombinant bacterial enzyme that rapidly hydrolyzes MTX to inactive
      metabolites, has become available for the treatment of HDMTX-induced renal
      dysfunction. CPDG(2) administration has been well tolerated and resulted in
      consistent and rapid reductions in plasma MTX concentrations by a median of 98.7%
      (range, 84%-99.5%). The early administration of CPDG(2) in addition to LV may be
      beneficial for patients with MTX-induced renal dysfunction and significantly
      elevated plasma MTX concentrations.

PMID- 16794249
TI  - Granzyme B, a novel mediator of allergic inflammation: its induction and release
      in blood basophils and human asthma.
AB  - Histamine, leukotriene C4, IL-4, and IL-13 are major mediators of allergy and
      asthma. They are all formed by basophils and are released in particularly large
      quantities after stimulation with IL-3. Here we show that supernatants of
      activated mast cells or IL-3 qualitatively change the makeup of granules of human
      basophils by inducing de novo synthesis of granzyme B (GzmB), without induction
      of other granule proteins expressed by cytotoxic lymphocytes (granzyme A,
      perforin). This bioactivity of IL-3 is not shared by other cytokines known to
      regulate the function of basophils or lymphocytes. The IL-3 effect is restricted
      to basophil granulocytes as no constitutive or inducible expression of GzmB is
      detected in eosinophils or neutrophils. GzmB is induced within 6 to 24 hours,
      sorted into the granule compartment, and released by exocytosis upon IgE
      dependent and -independent activation. In vitro, there is a close parallelism
      between GzmB, IL-13, and leukotriene C4 production. In vivo, granzyme B, but not
      the lymphoid granule marker granzyme A, is released 18 hours after allergen
      challenge of asthmatic patients in strong correlation with interleukin-13. Our
      study demonstrates an unexpected plasticity of the granule composition of mature
      basophils and suggests a role of granzyme B as a novel mediator of allergic
      diseases.

PMID- 16794250
TI  - Dangerous small B-cell clones.
AB  - The detection of a monoclonal immunoglobulin in serum or urine usually raises
      concerns about the size of the underlying B-cell-derived clone and possible
      systemic effects caused by its expansion. However, a small clone can synthesize a
      very toxic protein, producing devastating systemic damage and protean clinical
      presentations. The resulting "monoclonal component-related diseases," although
      difficult to diagnose, may be progressive and even fatal. The monoclonal protein
      can aggregate and deposit systemically as occurs in light-chain amyloidosis,
      monoclonal immunoglobulin deposition disease, crystal-storing histiocytosis, and
      monoclonal cryoglobulinemia. Alternatively, some monoclonal proteins possess
      antibody activity toward autogenous antigens and cause chronic cold agglutinin
      disease, mixed cryoglobulinemia, and peripheral neuropathies. Other humoral
      mediators may contribute to neuropathy in variant disorders such as the POEMS
      (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes)
      syndrome. The clone synthesizing the noxious monoclonal proteins is often small,
      and sensitive techniques may be required to detect these immunoglobulins. A delay
      in diagnosis can allow irreversible organ damage and dramatically shorten
      survival. Prompt recognition of suggestive signs and symptoms should trigger a
      thorough diagnostic approach to reach the correct diagnosis quickly, because this
      is the key to effective therapy. Although the treatment of these conditions is
      not optimal, significant advances have been made, improving the duration and
      quality of life.

PMID- 16794251
TI  - Gene expression of tumor angiogenesis dissected: specific targeting of colon
      cancer angiogenic vasculature.
AB  - Crucial to designing angiostatic and vascular targeting agents is the
      identification of target molecules. Because angiogenesis is not limited to
      pathologic conditions, careful evaluation of putative therapeutic targets is
      warranted to prevent adverse effects associated with impaired physiologic
      angiogenesis. To identify tumor-specific angiogenesis markers, we compared
      transcriptional profiles of angiogenic endothelial cells isolated from malignant
      and nonmalignant tissues with those of resting endothelial cells. We identified
      17 genes that showed specific overexpression in tumor endothelium but not in
      angiogenic endothelium of normal tissues, creating a therapeutic window for tumor
      vasculature-specific targeting. Antibody targeting of 4 cell-surface-expressed or
      secreted products (vimentin, CD59, HMGB1, IGFBP7) inhibited angiogenesis in vitro
      and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model
      significantly inhibited tumor growth and reduced microvessel density. Our results
      demonstrate the usefulness of the identification and subsequent targeting of
      specific tumor endothelial markers for anticancer therapy.

PMID- 16794252
TI  - Initiation of plasminogen activation on the surface of monocytes expressing the
      type II transmembrane serine protease matriptase.
AB  - uPA (urokinase-type plasminogen activator) activates plasminogen with high
      efficiency when bound to its cellular receptor uPAR, but only after a prolonged
      lag phase during which generated plasmin activates pro-uPA. How the activity of
      this proteolytic system might be rapidly initiated is unknown. We have now found
      that 2 monocytic cell lines display distinct patterns of plasminogen activation.
      U937 cells, but not THP-1 cells, displayed the expected lag phase, suggesting a
      constitutive initiation mechanism on the latter. This was shown to be due to the
      plasmin-independent activation of uPAR-bound pro-uPA by a cell surface-associated
      protease and to correlate with the expression of matriptase, a type II
      transmembrane serine protease that was highly expressed in THP-1 cells but
      undetectable in U937 cells. Kinetic analysis demonstrated that matriptase is a
      relatively poor activator of pro-uPA in solution, approximately 100-fold less
      efficient than plasmin (k(cat)/K(m) 1.16 x 10(5) M(-1)s(-1) cf 1.21 x 10(7) M(
      1)s(-1)). However, down-regulation of matriptase expression in THP-1 cells by
      siRNA reduced the activation of cell-associated pro-uPA and the subsequent rapid
      initiation of plasminogen activation by 76% to 93%. Matriptase was also found to
      be expressed by peripheral blood monocytes and may therefore be a specific
      mechanism for the rapid initiation and regulation of plasminogen activation by
      these cells.

PMID- 16794253
TI  - BASH-novel PKC-Raf-1 pathway of pre-BCR signaling induces kappa gene
      rearrangement.
AB  - The pre-B-cell receptor (pre-BCR) is thought to signal transcriptional activation
      of the immunoglobulin light (L) chain gene locus, proceeding to its V-J
      rearrangement. The pre-BCR signaling pathway for this process is largely unknown
      but may involve the adaptor protein BASH (BLNK/SLP-65). Here we report that the
      pre-B leukemia cell lines established from affected BASH-deficient mice rearrange
      kappaL-chain gene locus and down-regulate pre-BCR upon PMA treatment or BASH
      reconstitution. Analyses with specific inhibitors revealed that activation of
      novel PKC (nPKC) and MEK, but not Ras, is necessary for the rearrangement.
      Accordingly, retroviral transduction of active PKCeta, PKCepsilon, or Raf-1, but
      not Ras, induced the kappa gene rearrangement and expression in the pre-B-cell
      line. Tamoxifen-mediated BASH reconstitution resulted in the translocation of
      PKCeta to the plasma membrane and kappa chain expression. These data make evident
      that the Ras-independent BASH-nPKC-Raf-1 pathway of pre-BCR signaling induces the
      L-chain gene rearrangement and expression.

PMID- 16794254
TI  - Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency
      is linked to defective NEMO ubiquitination.
AB  - Ectodermal dysplasia with immune deficiency (EDI) is caused by alterations in
      NEMO (nuclear factor [NF]-kappaB essential modulator). Most genetic mutations are
      located in exon 10 and affect the C-terminal zinc finger domain. However, the
      biochemical mechanism by which they cause immune dysfunction remains
      undetermined. In this report, we investigated the effect of a cysteine-to
      arginine mutation (C417R) found in the NEMO zinc finger domain on dendritic cell
      (DC) function. Following CD40 stimulation of DCs prepared from 2 unrelated
      patients with the NEMO C417R mutation, we found NEMO ubiquitination was absent,
      and this was associated with preserved RelA but absent c-Rel activity. As a
      consequence, CD40 stimulated EDI DCs failed to synthesize the c-Rel-dependent
      cytokine interleukin-12, had impaired up-regulation of costimulatory molecules,
      and failed to support allogeneic lymphocyte proliferation in vitro. In contrast,
      EDI DCs stimulated with the TLR4 ligand lipopolysaccharide (LPS) showed normal
      downstream NF-kappaB activity, DC maturation, and NEMO ubiquitination. These
      findings show for the first time how mutations in the zinc finger domain of NEMO
      can lead to pathway specific defects in NEMO ubiquitination and thus immune
      deficiency.

PMID- 16794255
TI  - DIgR2, dendritic cell-derived immunoglobulin receptor 2, is one representative of
      a family of IgSF inhibitory receptors and mediates negative regulation of
      dendritic cell-initiated antigen-specific T-cell responses.
AB  - Dendritic cells (DCs) are specialized antigen-presenting cells that play crucial
      roles in the initiation and regulation of immune responses. Maturation and
      activation of DCs are controlled by a balance of the inhibitory and activating
      signals transduced through distinct surface receptors. Many inhibitory receptors
      expressed by DCs have been identified, whereas the new members and their
      functions need further investigation. In this study, we functionally
      characterized DC-derived immunoglobulin receptor 2 (DIgR2) as a novel
      representative of a family of inhibitory receptors belonging to the
      immunoglobulin superfamily. We show that DIgR2 contains 2 immunoreceptor tyrosine
      based inhibitory motifs (ITIMs) within its cytoplasmic region and that DIgR2
      associates with Src homology-2 domain-containing protein tyrosine phosphatases-1
      (SHP-1). Blockade of DIgR2 on DCs by pretreatment with DIgR2-Ig fusion protein or
      by silencing with specific small interfering RNA enhances DC-initiated T-cell
      proliferation and antigen-specific T-cell responses both in vitro and in vivo.
      Furthermore, immunization of mice with antigen-pulsed, DIgR2-silenced DCs elicits
      more potent antigen-specific CD4+ and CD8+ T-cell responses, thus protecting the
      vaccinated mice from tumor challenge more effectively. Our data suggest that
      DIgR2 is a functionally inhibitory receptor and can mediate negative signaling to
      regulate DC-initiated antigen-specific T-cell responses.

PMID- 16794256
TI  - Heparin and fibroblast growth factors affect surfactant protein gene expression
      in type II cells.
AB  - The stimulation and maintenance of the pulmonary alveolar type II cell's capacity
      to biosynthesize, store, and secrete surfactant proteins (SPs) are modulated to a
      great extent by growth factors, extracellular matrix (ECM) components, and
      hormones. It is possible that differences in ECM composition, as exist between
      type I and II cells normally or as might occur with excessive cell surface
      shedding during inflammation or injury states, may specifically alter SP
      expression. Here, isolated type II cells were exposed to the model sulfated ECM
      heparin; desulfated heparin; and/or fibroblast growth factor (FGF)-1, -2, or -7
      for 24 h to examine by quantitative real-time polymerase chain reaction their
      effects on SP gene expression. Aquaporin 5 (AQP-5) gene expression was also
      examined as a phenotypic marker for the type I cell. SP-B mRNA abundance was
      increased 4- to 8-fold by all three FGFs. Heparin at low concentrations (5
      microg/ml) or desulfated heparin at high concentrations (500 microg/ml) enhanced
      the effects of FGF-2 and -7, while high heparin concentrations (500 microg/ml)
      were inhibitory. In contrast, SP-B mRNA abundance was increased by heparin in a
      dose- and sulfation-dependent manner when used in combination with FGF-1. SP-C
      and AQP-5 mRNA levels were increased by heparin alone in a dose- and sulfation
      dependent manner, while all FGFs lacked effect on SP-C or AQP-5 mRNA levels.
      These data indicate that heparin can be stimulatory to SP gene expression
      depending on concentration, degree of sulfation, and surrounding FGF environment,
      and that heparin plays a significant role in modulating alveolar epithelial cell
      phenotype in vitro.

PMID- 16794258
TI  - Airway hyperreactivity in exacerbation of chronic asthma is independent of
      eosinophilic inflammation.
AB  - We have developed an animal model to investigate the mechanisms underlying an
      acute exacerbation of chronic asthma. Sensitized BALB/c mice were exposed to
      aerosolized ovalbumin, either as chronic low-level challenge (mass concentration
      approximately 3 mg/m(3)) for 4 wk, a single moderate-level challenge
      (approximately 30 mg/m(3)), or chronic low-level followed by single moderate
      level challenge (the acute exacerbation group). Compared with animals receiving
      chronic challenge alone, mice in the acute exacerbation group exhibited a more
      marked inflammatory response, with involvement of intrapulmonary airways and lung
      parenchyma, and increased numbers of lymphocytes and eosinophils in
      bronchoalveolar lavage fluid. They also developed airway hyperreactivity (AHR) to
      methacholine, demonstrable as increased transpulmonary resistance and decreased
      compliance. This pattern of AHR was absent in chronically challenged animals, but
      was also present in animals given single moderate-level challenge. However,
      compared with animals receiving a single moderate-level challenge, inflammation
      and AHR were induced more rapidly in the acute exacerbation group. Eosinophil
      deficient GATA1 Deltadbl mice exhibited undiminished AHR in the acute
      exacerbation model. We conclude that in mice with pre-existing airway lesions
      resembling mild chronic asthma, exposure to a moderately high concentration of
      inhaled antigen induces features of an acute exacerbation. The inflammatory
      response involves distal airways and is associated with a distinct pattern of
      AHR, which develops independent of the enhanced eosinophilic inflammation.

PMID- 16794257
TI  - Quercetin blocks airway epithelial cell chemokine expression.
AB  - Quercetin (3,3',4',5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor
      of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized
      that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase
      dependent mechanisms. Pretreatment with quercetin and the PI 3-kinase inhibitor
      LY294002 each reduced TNF-alpha-induced IL-8 and monocyte chemoattractant protein
      (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells.
      Quercetin also inhibited TNF-alpha-induced PI 3-kinase activity, Akt
      phosphorylation, intracellular H(2)O(2) production, NF-kappaB transactivation, IL
      8 promoter activity, and steady-state mRNA levels, consistent with the notion
      that quercetin inhibits chemokine expression by attenuating NF-kappaB
      transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced
      TNF-alpha-induced chemokine secretion in the presence of the transcriptional
      inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation
      initiation factor (eIF)-2alpha, suggesting that quercetin attenuates chemokine
      expression by post-transcriptional as well as transcriptional mechanisms.
      Finally, we tested the effects of quercetin in cockroach antigen-sensitized and 
      challenged mice. These mice show MCP-1-dependent airways hyperresponsiveness and
      inflammation. Quercetin significantly reduced lung MCP-1 and methacholine
      responsiveness. We conclude that quercetin blocks airway cell chemokine
      expression via transcriptional and post-transcriptional pathways.

PMID- 16794259
TI  - Muscle wasting and impaired muscle regeneration in a murine model of chronic
      pulmonary inflammation.
AB  - Muscle wasting and increased circulating levels of inflammatory cytokines,
      including TNF-alpha, are common features of chronic obstructive pulmonary
      disease. To investigate whether inflammation of the lung is responsible for
      systemic inflammation and muscle wasting, we adopted a mouse model of pulmonary
      inflammation resulting from directed overexpression of a TNF-alpha transgene
      controlled by the surfactant protein C (SP-C) promoter. Compared with wild-type
      mice, SP-C/TNF-alpha mice exhibited increased levels of TNF-alpha in the
      circulation and increased endogenous TNF-alpha expression in skeletal muscle,
      potentially reflecting an amplificatory response to circulating TNF-alpha.
      Decreased muscle and body weights observed in SP-C/TNF-alpha mice were indicative
      of muscle wasting. Further evaluation of the SP-C/TNF-alpha mouse musculature
      revealed a decreased muscle regenerative capacity, shown by attenuated myoblast
      proliferation and differentiation in response to reloading of disuse-atrophied
      muscle, which may contribute to skeletal muscle wasting. Importantly, incubation
      of cultured myoblasts with TNF-alpha also resulted in elevated TNF-alpha mRNA
      levels and inhibition of myoblast differentiation. Collectively, our results
      demonstrate that chronic pulmonary inflammation results in muscle wasting and
      impaired muscle regeneration in SP-C/TNF-alpha mice, possibly as a consequence of
      an amplificatory TNF-alpha expression circuit extending from the lung to skeletal
      muscle.

PMID- 16794260
TI  - Induction of the plasminogen activator system by mechanical stimulation of human
      bronchial epithelial cells.
AB  - Mechanical stimulation of the airway epithelium, as would occur during
      bronchoconstriction, is a potent stimulus and can activate profibrotic pathways.
      We used DNA microarray technology to examine gene expression in compressed normal
      human bronchial epithelial cells (NHBE). Compressive stress applied continuously
      over an 8-h period to NHBE cells led to the upregulation of several families of
      genes, including a family of plasminogen-related genes that were previously not
      known to be regulated in this system. Real-time PCR demonstrated a peak increase
      in gene expression of 8.0-fold for urokinase plasminogen activator (uPA), 16.2
      fold for urokinase plasminogen activator receptor (uPAR), 4.2-fold for
      plasminogen activator inhibitor-1 (PAI-1), and 3.9-fold for tissue plasminogen
      activator (tPA). Compressive stress also increased uPA protein levels in the cell
      lysates (112.0 versus 82.0 ng/ml, P = 0.0004), and increased uPA (4.7 versus 3.3
      ng/ml, P = 0.02), uPAR (1.3 versus 0.86 ng/ml, P = 0.007), and PAI-1 (50 versus
      36 ng/ml, P = 0.006) protein levels in cell culture media. Functional studies
      demonstrated increased urokinase-dependent plasmin generation in compression
      stimulated cells (0.0090 versus 0.0033 OD/min, P = 0.03). In addition,
      compression led to increased activation of matrix metalloproteinase (MMP)-9 and
      MMP-2 in a urokinase-dependent manner. In postmortem human lung tissue, we
      observed an increase in epithelial uPA and uPAR immunostaining in the airways of
      two patients who died in status asthmaticus compared with minimal
      immunoreactivity noted in airways from seven lung donors without asthma. Together
      these observations suggest an integrated response of airway epithelial cells to
      mechanical stimulation, acting through the plasminogen-activating system to
      modify the airway microenvironment.

PMID- 16794262
TI  - Engraftment of donor-derived epithelial cells in multiple organs following bone
      marrow transplantation into newborn mice.
AB  - Bone marrow-derived cells (BMDCs) can engraft as epithelial cells throughout the
      body, including in the lung, liver, and gastrointestinal (GI) tract following
      transplantation into lethally irradiated adult recipients. Except for rare
      disease models in which marrow-derived epithelial cells have a survival advantage
      over endogenous cells, the currently attained levels of epithelial engraftment of
      BMDCs are too low to be of therapeutic benefit. Here we tested whether the degree
      of bone marrow to epithelial engraftment would be higher if bone marrow
      transplantation (BMT) were performed on 1-day-old mice, when tissues are
      undergoing rapid growth and remodeling. BMT into newborn mice after multiple
      different regimens allowed for robust hematopoietic engraftment, as well as the
      development of rare donor-derived epithelial cells in the GI tract and lung but
      not in the liver. The highest epithelial engraftment (0.02%) was obtained in mice
      that received a preparative regimen of two doses of busulfan in utero. When BMDCs
      were transplanted into myelosuppressed newborn mice that lacked expression of the
      cystic fibrosis transmembrane conductance regulator (CFTR) protein, the chloride
      channel that is not functional in patients with cystic fibrosis, the engrafted
      mice showed partial restoration of CFTR channel activity, suggesting that marrow
      derived epithelial cells in the GI tract were functional. However, BMT into
      newborn mice, regardless of the myeloablative regimen used, did not increase the
      number of bone marrow-derived epithelial cells over that which occurs after BMT
      into lethally irradiated adult mice.

PMID- 16794261
TI  - Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in
      lungs, is regulated by Nrf2.
AB  - Disruption of NF-E2-related factor (Nrf2), a redox-sensitive basic leucine zipper
      transcription factor, causes early-onset and more severe emphysema due to chronic
      cigarette smoke. Nrf2 determines the susceptibility of lungs to cigarette smoke
      induced emphysema in mice through the transcriptional induction of numerous
      antioxidant genes. The lungs of Nrf2-/- mice have higher oxidative stress as
      evident from the increased levels of lipid peroxidation (4-hydroxy-2-nonenal) and
      oxidative DNA damage (7,8-dihydro-8-Oxo-2'deoxyguanosine) in response to
      cigarette smoke. Glutathione peroxidases (GPX) are the primary antioxidant
      enzymes that scavenge hydrogen peroxide and organic hydroperoxides. Among the
      five GPX isoforms, expression of GPX2 was significantly induced at both mRNA and
      protein levels in the lungs of Nrf2+/+ mice, in response to cigarette smoke.
      Activation of Nrf2 by specific knock down of the cytosolic inhibitor of Nrf2,
      Keap1, by small inhibitory RNA (siRNA) upregulated the expression of GPx2,
      whereas Nrf2 siRNA down-regulated the expression of GPX2 in lung epithelial
      cells. An ARE sequence located in the 5' promoter-flanking region of exon 1 that
      is highly conserved between mouse, rat, and human was identified. Mutation of
      this ARE core sequence completely abolished the activity of promoter-reporter
      gene construct. The binding of Nrf2 to the GPX2 antioxidant response element was
      confirmed by chromatin immunoprecipation, electrophoretic mobility shift assays,
      and site-directed mutagenesis. This study shows that GPX2 is the major oxidative
      stress-inducible cellular GPX isoform in the lungs, and that its basal as well as
      inducible expression is dependent on Nrf2.

PMID- 16794263
TI  - Concise review: scientific and ethical roadblocks to human embryonic stem cell
      therapy.
AB  - Despite the identified therapeutic potential of embryonic stem cells for treating
      human disease and injury, a number of roadblocks, scientific and ethical, stand
      in the way of progress toward this goal. We identify six areas of particular
      interest: tumorigenicity, animal product contamination, genetic compatibility,
      funding, cell type for transplantation, "embryo-friendly" derivation methods and
      discuss avenues for moving beyond the difficulties.

PMID- 16794264
TI  - Concise review: recent advances on the significance of stem cells in tissue
      regeneration and cancer therapies.
AB  - In this study, we report on recent advances on the functions of embryonic, fetal,
      and adult stem cell progenitors for tissue regeneration and cancer therapies. We
      describe new procedures for derivation and maturation of these stem cells into
      the tissue-specific cell progenitors. The localization of the adult stem cells
      and their niches, as well as their implication in the tissue repair after
      injuries and during cancer progression, are also described. The emphasis is on
      the interactions among certain developmental signaling factors, such as hormones,
      epidermal growth factor, hedgehog, Wnt/beta-catenin, and Notch. These factors and
      their pathways are involved in the stringent regulation of the self-renewal
      and/or differentiation of adult stem cells. Novel strategies for the treatment of
      both diverse degenerating disorders, by cell replacement, and some metastatic
      cancer types, by molecular targeting multiple tumorigenic signaling elements in
      cancer progenitor cells, are also illustrated.

PMID- 16794265
TI  - Immunogenicity and engraftment of mouse embryonic stem cells in allogeneic
      recipients.
AB  - Embryonic stem cells (ESCs) are pluripotent and therefore able to differentiate
      both in vitro and in vivo into specialized tissues under appropriate conditions,
      a property that could be exploited for cellular therapies. However, the
      immunological nature of these cells in vivo has not been well understood. In
      vitro, mouse-derived ESCs fail to stimulate T cells, but they abrogate ongoing
      alloresponses by a process that requires cell-cell contact. We further show that
      despite a high expression of the NKG2D ligand retinoic acid early inducible-1 by
      mouse ESCs, they remain resistant to natural killer cell lysis. In vivo,
      allogeneic mouse ESCs populate the thymus, spleen, and liver of sublethally
      irradiated allogeneic host mice, inducing apoptosis to T cells and establishing
      multilineage mixed chimerism that significantly inhibits alloresponses to donor
      major histocompatibility complex antigens. Immunohistochemical imaging revealed a
      significant percentage of ESC-derived cells in the splenic marginal zones, but
      not in the follicles. Taken together, the data presented here reveal that
      nondifferentiated mouse embryonic stem cells are non-immunogenic and appear to
      populate lymphoid tissues in vivo, leading to T-cell deletion by apoptosis.

PMID- 16794266
TI  - A new technique for the isolation and surface immobilization of mesenchymal stem
      cells from whole bone marrow using high-specific DNA aptamers.
AB  - Adult mesenchymal stem cells (aMSCs) are a stem cell population present in bone
      marrow, which can be isolated and expanded in culture and characterized. Due to
      the lack of specific surface markers, it is difficult to separate the MSCs from
      bone marrow directly. Here, we present a novel method using high-specific nucleic
      acids called aptamers. Porcine MSCs were used as a target to generate aptamers by
      combinatorial chemistry out of a huge random library with in vitro technology
      called systematic evolution of ligands by exponential enrichment (SELEX). After
      cloning and sequencing, the binding affinity was detected using a cell-sorting
      assay with streptavidin-coated magnetic microbeads. We also used 12-well plates
      immobilized with aptamers to fish out MSCs from the cell solution and a
      fluorescein isothiocyanate-labeled aptamer to sort MSCs from bone marrow using
      high-speed fluorescence-activated cell sorting. The cells showed high potency to
      differentiate into osteogenic, as well as into adipogenic, lineages with typical
      morphological characteristics. Surface marker staining showed that the attached
      cells were CD29(+), CD44(+), CD45(-), CD90(+), SLA class I(+), SLA DQ(-), and SLA
      DR(-). Compared with existing methods, this study established a novel, rapid, and
      efficient method for direct isolation of aMSCs from porcine bone marrow by using
      an aptamer as a probe to fish out the aMSCs. This new application of aptamers can
      facilitate aMSC isolation and enrichment greatly, thereby enhancing the rate of
      aMSC-derived cells after in vitro differentiation for various applications in the
      emerging field of tissue engineering and regenerative medicine.

PMID- 16794267
TI  - Endothelial progenitor cell release into circulation is triggered by hyperoxia
      induced increases in bone marrow nitric oxide.
AB  - Endothelial progenitor cells (EPC) are known to contribute to wound healing, but
      the physiologic triggers for their mobilization are often insufficient to induce
      complete wound healing in the presence of severe ischemia. EPC trafficking is
      known to be regulated by hypoxic gradients and induced by vascular endothelial
      growth factor-mediated increases in bone marrow nitric oxide (NO). Hyperbaric
      oxygen (HBO) enhances wound healing, although the mechanisms for its therapeutic
      effects are incompletely understood. It is known that HBO increases nitric oxide
      levels in perivascular tissues via stimulation of nitric oxide synthase (NOS).
      Here we show that HBO increases bone marrow NO in vivo thereby increasing release
      of EPC into circulation. These effects are inhibited by pretreatment with the NOS
      inhibitor l-nitroarginine methyl ester (l-NAME). HBO-mediated mobilization of EPC
      is associated with increased lower limb spontaneous circulatory recovery after
      femoral ligation and enhanced closure of ischemic wounds, and these effects on
      limb perfusion and wound healing are also inhibited by l-NAME pretreatment. These
      data show that EPC mobilization into circulation is triggered by hyperoxia
      through induction of bone marrow NO with resulting enhancement in ischemic limb
      perfusion and wound healing.

PMID- 16794268
TI  - Polyamines modulate nitric oxide production and COX-2 gene expression in response
      to mechanical loading in human adipose tissue-derived mesenchymal stem cells.
AB  - For bone tissue engineering, it is important that mesenchymal stem cells (MSCs)
      display a bone cell-like response to mechanical loading. We have shown earlier
      that this response includes increased nitric oxide (NO) production and
      cyclooxygenase-2 (COX-2) gene expression, both of which are intimately involved
      in mechanical adaptation of bone. COX-2 gene expression is likely regulated by
      polyamines, which are organic cations implicated in cell proliferation and
      differentiation. This has led to the hypothesis that polyamines may play a role
      in the response of adipose tissue-derived MSCs (AT-MSCs) to mechanical loading.
      The aim of this study was to investigate whether genes involved in polyamine
      metabolism are regulated by mechanical loading and to study whether polyamines
      modulate mechanical loading-induced NO production and COX-2 gene expression in
      human AT-MSCs. Human AT-MSCs displayed a bone cell-like response to mechanical
      loading applied by pulsating fluid flow (PFF), as demonstrated by increased NO
      production and increased gene expression of COX-2. Furthermore, PFF increased
      gene expression of spermidine/spermine N (1)-acetyltransferase, which is involved
      in polyamine catabolism, suggesting that mechanical loading modulates polyamine
      levels. Finally, the polyamine spermine was shown to inhibit both PFF-induced NO
      production and COX-2 gene expression, suggesting that polyamines modulate the
      response of human AT-MSCs to mechanical loading. In conclusion, this is the first
      study implicating polyamines in the response of human AT-MSCs to mechanical
      loading, creating opportunities for the use of polyamines in tissue engineering
      approaches targeting skeletal defects.

PMID- 16794269
TI  - Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow
      progenitor cells in patients with chronic ischemic cardiomyopathy: cell
      isolation, adherence to the infarcted area, and body distribution.
AB  - Central issues in intracoronary infusion (ICI) of bone marrow (BM)-cells to
      damaged myocardium for improving cardiac function are the cell number that is
      feasible and safe to be administrated as well as the retention of cells in the
      target area. Our study addressed these issues in eight patients with chronic
      ischemic cardiomyopathy undergoing ICI of selected BM-progenitors. We could
      immunomagnetically isolate 0.8 +/- 0.32 x 10(7) CD133(+) cells and 0.75 +/- 0.24
      x 10(7) CD133(-)CD34(+) cells from 310 +/- 40 ml BM. After labeling these cells
      with (99m)Tc-hexamethylpropylenamineoxime, they were infused into the infarct
      related artery without any complication. Scintigraphic images 1 (eight patients)
      and 24 hours (four patients) after ICI revealed an uptake of 9.2% +/- 3.6 and
      6.8% +/- 2.4 of the total infused radioactivity in the infarcted area of the
      heart, respectively; the remaining activity was distributed mainly to liver and
      spleen. We conclude that through ICI of CD133(+) and CD133(-)CD34(+) BM
      progenitors a significant number of them are preferentially attracted to and
      retained in the chronic ischemic myocardium.

PMID- 16794271
TI  - The right incentives for high-quality, affordable care: a new form of regulated
      competition.

PMID- 16794272
TI  - Outbreak of E. coli 0157:H7 infections associated with a brand of beefburgers in
      France.

PMID- 16794273
TI  - Outbreak update: Salmonella Goldcoast infections in tourists returning from
      Majorca.

PMID- 16794274
TI  - Denmark decides not to introduce hepatitis B into the childhood vaccination
      programme.

PMID- 16794275
TI  - Denmark scales up hepatitis B screening and vaccination for risk groups.

PMID- 16794277
TI  - Re-emergence of syphilis in Sweden: results from a surveillance study for 2004.

PMID- 16794276
TI  - Salmonella Typhimurium DT104 outbreak linked to imported minced beef, Norway,
      October-November 2005.

PMID- 16794278
TI  - Recent outbreak of rabies infections in Brazil transmitted by vampire bats.

PMID- 16794279
TI  - Bats as the reservoir for outbreaks of emerging infectious diseases.

PMID- 16794280
TI  - Europe makes progress in preparing for influenza pandemic, but further work
      needed.
AB  - Progress has been made in influenza pandemic preparedness in Europe in the past
      six month.

PMID- 16794281
TI  - Successful reduction of human Salmonella Enteritidis infection in England and
      Wales.

PMID- 16794282
TI  - Surveillance of surgical site infection in orthopaedic surgery is useful in
      tackling hospital-acquired infections in England.

PMID- 16794283
TI  - Increase of gonococcal quinolone resistance in the Netherlands from 2002-2004.

PMID- 16794284
TI  - Transmission of HIV/AIDS in Europe continuing.

PMID- 16794285
TI  - Further escalation of the global HIV/AIDS epidemic in 2005 but one million
      patients on antiretroviral therapy.
AB  - AIDS is estimated to be responsible for 25 million deaths since 1981.

PMID- 16794286
TI  - Rubella outbreak in an unvaccinated religious community in the Netherlands leads
      to cases of congenital rubella syndrome.

PMID- 16794287
TI  - US study suggests universal vaccination of children with pneumococcal conjugate
      vaccine is beneficial for adults.

PMID- 16794288
TI  - Intravenous artesunate recommended for patients with severe malaria: position
      statement from TropNetEurop.

PMID- 16794289
TI  - Recent trends in new diagnoses of HIV infections in Switzerland: probable
      increase in MSM despite an overall decrease.

PMID- 16794290
TI  - International outbreak of Salmonella Goldcoast infection in tourists returning
      from Majorca, September-October 2005: final summary.

PMID- 16794291
TI  - An outbreak of cryptosporidiosis in Wales, November 2005.

PMID- 16794292
TI  - H5N1 avian influenza: update on the global situation.

PMID- 16794293
TI  - Hajj 2006: communicable disease and other health risks and current official
      guidance for pilgrims.

PMID- 16794294
TI  - European drugs agency highlights trends in drug use and problems affecting drug
      users.

PMID- 16794295
TI  - Outbreak of wound botulism in injecting drug users in Germany, October-December
      2005.

PMID- 16794297
TI  - E-alert 9 December: Malaria cases and deaths in UK travellers returning from The
      Gambia.

PMID- 16794296
TI  - Common Ground: a pandemic influenza simulation exercise for the European Union,
      23-24 November 2005.

PMID- 16794300
TI  - Outbreak of legionnaires disease in Torrevieja, Spain, November-December 2005.

PMID- 16794302
TI  - Large E. coli O157 outbreak in Ireland, October-November 2005.

PMID- 16794303
TI  - Lymphogranuloma venereum (LGV) serotype L2 in Switzerland, 2003-2005.

PMID- 16794304
TI  - HIV and other sexually transmitted infections in the United Kingdom: an update
      2005.

PMID- 16794305
TI  - Anti-inflammatory metabolite production in the gut from the consumption of
      probiotic yogurt containing Bifidobacterium animalis subsp. lactis LKM512.
AB  - There is little evidence for a relationship between probiotic metabolites and
      host cytokine production. We investigated in the present study the possibility
      that anti-inflammatory metabolites can be produced in the gut by LKM512 yogurt
      consumption by using murine macrophage-like J774.1 cells and extracts prepared
      from the feces of elderly volunteers. These volunteers' acute inflammation had
      been inhibited by LKM512 yogurt consumption in a previous test. The tumor
      necrosis factor (TNF)-alpha production elicited in J774.1 cells stimulated by
      lipopolysaccharide (LPS) and in the fecal extracts obtained during the period of
      LKM512 yogurt consumption was significantly decreased (p<0.05) than the pre
      consumption baseline level. These findings and previous data enable us to
      conclude that intestinal bacterial metabolites produced by LKM512 yogurt
      consumption contributed to suppressing the inflammatory cytokine produced by
      macrophages and that one of the anti-inflammatory metabolites in the fecal
      extracts was likely to have been a polyamine.

PMID- 16794307
TI  - Assembly of staphylococcal leukocidin into a pore-forming oligomer on detergent
      resistant membrane microdomains, lipid rafts, in human polymorphonuclear
      leukocytes.
AB  - Staphylococcal leukocidin (Luk) consists of LukS and LukF, which cooperatively
      lyse human polymorphonuclear leukocytes (HPMNLs), monocytes, and macrophages.
      Here we found that LukS and LukF assembles into hetero-oligomeric pore complexes
      on the detergent-resistant membrane microdomains, lipid rafts of HPMNLs. When
      HPMNLs were treated with LukS alone, 24% of the added LukS was localized in lipid
      rafts. Furthermore, in HPMNLs treated with both LukS and LukF simultaneously,
      about 90% of high molecular-mass complexes of 100 kDa, which consists of LukS and
      LukF, were detected in the lipid raft fractions. In contrast, in HPMNLs treated
      with LukF alone, LukF was not localized in lipid rafts despite binding to the
      target cell membranes. Ten mM methyl-beta-cyclodextrin, a dysfunctioning agent of
      lipid rafts, completely inhibited assembly of Luk on lipid rafts, and resulted in
      null leukocytolytic activity of Luk. Hence, we concluded that assembly of LukS
      and LukF into the pore-complex occurs in lipid rafts in HPMNLs and that LukF can
      bind to LukS, which had already bound to lipid rafts, to assemble into hetero
      oligomers.

PMID- 16794306
TI  - Intron-dependent accumulation of mRNA in Coriolus hirsutus of lignin peroxidase
      gene the product of which is involved in conversion/degradation of
      polychlorinated aromatic hydrocarbons.
AB  - The homobasidiomycete Coriolus hirsutus coding sequences of a lignin peroxidase
      (LiP) gene (lip, containing six (I-VI) introns), a lip cDNA (lipc), and three
      lipc derivatives containing one (I), three (I-III), or five (I-V) introns were
      inserted into chromosome-integrating expression vector. These recombinant
      plasmids were introduced into C. hirustus monokaryotic strain. The transformant
      carrying the promoter-lipc-terminator cassette did not contain enough mRNA
      molecules to be detectable by Northern-blot analysis. On the other hand, all the
      transformants carrying cassettes of genomic lip and intron(s)-containing lipc
      sequences contained sufficient amounts of mRNAs to be easily detected by Northern
      blot analysis. LiP activities in the culture supernatants of these transformants
      were found to be about five times as high as those of transformants carrying the
      lipc cassette (or no cassette). The culture supernatants of the transformants
      with high LiP activity showed remarkably high conversion activity toward
      pentachlorophenol (PCP) and degradation activity toward 2,7-dichlorodibenzo-p
      dioxin (2,7-DCDD). These results indicate that at least one intron (intron I) is
      required for accumulation of lip mRNA and its subsequent translational expression
      in C. hirsutus.

PMID- 16794308
TI  - Characterization of Sulfolobus solfataricus 2-keto-3-deoxy-D-gluconate kinase in
      the modified Entner-Doudoroff pathway.
AB  - The thermoacidophilic archaeon Sulfolobus solfataricus is known to utilize D
      glucose via the nonphosphorylated Entner-Doudoroff (ED) pathway. But, the genome
      database shows that this microorganism has a gene (kdgK) encoding 2-keto-3-deoxy
      D-gluconate (KDG) kinase (KDGK) which phosphorylates KDG to 2-keto-3-deoxy-6
      phosphogluconate. Interestingly, kdgK and three other genes in the modified ED
      pathway are organized as an operon-like structure. In this study, we report
      confirmation of the catalytic activity of the S. solfataricus KDGK protein. We
      also found that the kdgK gene was transcribed as polycistronic transcripts.
      Proteome analysis of cell lysate revealed that all gene products in the kdgK
      operon were expressed as functional proteins. These results strongly indicate
      that S. solfataricus metabolizes D-glucose via the 'partially' nonphosphorylated
      ED pathway. A purified recombinant S. solfataricus KDGK had K(m) and k(cat)
      values of 0.14 mM and 60.8 s(-1) respectively for KDG, and showed maximal
      activity at temperatures between 70 and 80 degrees C and pHs between 7.0 and 8.0.

PMID- 16794309
TI  - Effects of uptake of flavonoids on oxidative stress induced by hydrogen peroxide
      in human intestinal Caco-2 cells.
AB  - The relation between the uptake of flavonoids and the response of human colon
      adenocarcinoma Caco-2 cells exposed to oxidative stress induced by hydrogen
      peroxide (H(2)O(2)) was examined. Flavonoid aglycones were incorporated into Caco
      2 cells in a concentration- and time-dependent manner, but neither glycosides nor
      unstable myricetin were incorporated into the cells. The incorporated flavonoids
      reduced the reactive oxygen species (ROS) induced by H(2)O(2) in the cells in
      proportion to the amount incorporated and the radical scavenging activity of
      flavonoids. But, flavonoids with high radical scavenging activity also generated
      H(2)O(2). The activity decreasing intracellular ROS was inversely related to the
      H(2)O(2) scavenging activity of flavonoids. Therefore, the decrease in the amount
      of intracellular ROS induced by H(2)O(2) was not directly due to the scavenging
      of H(2)O(2), but rather to the scavenging of ROS generated from H(2)O(2). These
      results suggest that strong antioxidative flavonoids have both a cytoprotective
      effect owing to the scavenging of ROS and cytotoxic effect caused by the
      generation of H(2)O(2).

PMID- 16794310
TI  - Differentiation of mouse p19 embryonic carcinoma stem cells injected into an
      empty zebrafish egg chorion in a microfluidic device.
AB  - Mouse P19 embryonic carcinoma (EC) stem cells were xenotransplanted into the
      emptied chorion, the transparent envelope of a fertilized zebrafish egg (rather
      than mouse native zona pellucida) combined with a microfluidic device to study
      P19 EC cell differentiation in the chorion biomaterial. A distilled-water jet was
      used to remove the innate yolk and perivitelline inner mass from the chorion. P19
      EC cells were injected into the emptied chorion using a micropipette, and they
      were subsequently cultured until the inner space of the chorion became completely
      occupied by cells. A simple microfluidic device was used for handling convenience
      and effective experiment. At d15, we found neural cells in the outer layer of the
      cell mass and beating cardiomyocytes in the inner layer of the large embryoid
      body. We propose that even though the species are different, the external innate
      membranes developed for embryo protection represent a useful type of ECM.

PMID- 16794311
TI  - Comparison of the effects of di(2-ethylhexyl)phthalate, a peroxisome
      proliferator, on the vitamin metabolism involved in the energy formation in rats
      fed with a casein or gluten diet.
AB  - In order to find an alleviation method for the adverse effect of environmental
      endocrine disrupters, we studied the effects of the putative endocrine disrupter
      and peroxisome proliferator, di(2-ethylhexyl)phthalate (DEHP), on animal growth
      and vitamin metabolism. It is known that the effects of chemical compounds such
      as xenobiotics differ according to the dietary protein source. We compared the
      effects of dietary DEHP administration on rats fed with a diet containing milk
      casein or wheat gluten. The increased conversion ratio of tryptophan to
      nicotinamide by DEHP administration was significantly higher in the casein group
      than in the gluten group. We also investigated the effects of DEHP on the urinary
      excretion of other vitamins. DEHP administration resulted in decreased urinary
      excretion of vitamin B(1), vitamin B(2), and pantothenic acid.

PMID- 16794312
TI  - Synthesis of a glycosylated peptide thioester by the Boc strategy and its
      application to segment condensation.
AB  - The synthesis of a chitobiosylated peptide thioester by the t-butoxycarbonyl
      (Boc) strategy is demonstrated. Boc-Asn carrying benzyl-protected chitobiose was
      introduced during application of the Boc mode solid-phase method. HF treatment of
      the resulting protected peptide resin gave the desired chitobiosylated peptide
      thioester. This thioester was used to prepare the peptide sequence derived from
      extracellular matrix metalloproteinase inducers (emmprin) (34-94), (34-118) and
      (22-118) by the thioester segment condensation method. The conformation of these
      glycopeptides is characterized by circular dichroism (CD) spectral measurement.

PMID- 16794313
TI  - Heterogeneity in regeneration of bacteriorhodopsin from bacterio-opsin and all
      trans retinal at high temperatures: implications for dynamic structural
      fluctuations.
AB  - Measurements of regeneration kinetics were performed in order to investigate the
      regeneration mechanisms of bacteriorhodopsin (bR) from thermally unfolded
      bacterio-opsin (bO) and all-trans retinal. Regeneration kinetics data were
      successfully fitted to a single exponential function when regeneration was
      performed at 25 degrees C after incubation at high temperatures. Conversely, the
      process of regeneration after the addition of retinal to bO at high temperatures
      occurred at two different rate constants. These findings strongly suggest that
      the slower regeneration of bR at high temperatures occurs as a result of dynamic
      structural fluctuation of bO, whereas the faster process corresponds to
      regeneration from bO, which retains a native structure capable of retinal
      binding.

PMID- 16794314
TI  - Glycoform analysis of N-glycans linked to glycoproteins expressed in rice culture
      cells: predominant occurrence of complex type N-glycans.
AB  - Although it has been found that plant endo-beta-N-acetylglucosaminidase shows
      strong activity towards denatured glycoproteins and glycopeptides with high
      mannose type N-glycans and free high-mannose type N-glycans bearing the
      chitobiosyl unit, the endogenous substrates for plant endoglycosidase have not
      yet been identified. Recently we purified and characterized an endo-beta-N
      acetylglucosaminidase from rice culture cells and identified the gene encoded.
      Furthermore, we found structural features of free N-glycans in the cells,
      indicating that high-mannose type species (Man(9-5)GlcNAc(1)) occur at
      concentration of several micromolar (microM). Hence, in this study we analyzed
      glycoform of N-glycans linked to glycoproteins expressed in rice culture cells to
      see whether endogenous glycoproteinous substrate occurs in reasonable amounts.
      Structural analysis revealed that more than 95% of total N-glycans linked to
      glycoproteins in the rice cells had the plant complex type structure, including
      Lewis a epitope-harboring type, although high-mannose type structures account for
      less than 5% of total N-glycans.

PMID- 16794315
TI  - Iejimalides show anti-osteoclast activity via V-ATPase inhibition.
AB  - Iejimalides (IEJLs), 24-membered macrolides, are potent antitumor compounds, but
      their molecular targets remain to be revealed. In the course of screening, we
      identified IEJLs as potent osteoclast inhibitors. Since it is known that
      osteoclasts are sensitive to vacuolar H(+)-ATPase (V-ATPase) inhibitor, we
      investigated the effect of IEJLs on V-ATPases. IEJLs inhibited the V-ATPases of
      both mammalian and yeast cells in situ, and of yeast V-ATPases in vitro. A
      bafilomycin-resistant yeast mutant conferred IEJL resistance, suggesting that
      IEJLs bind a site similar to the bafilomycins/concanamycins-binding site. These
      results indicate that IEJLs are novel V-ATPase inhibitors, and that antitumor and
      antiosteporotic activities are exerted via V-ATPase inhibition.

PMID- 16794316
TI  - Efficient production of 2-deoxyribose 5-phosphate from glucose and acetaldehyde
      by coupling of the alcoholic fermentation system of Baker's yeast and
      deoxyriboaldolase-expressing Escherichia coli.
AB  - 2-Deoxyribose 5-phosphate production through coupling of the alcoholic
      fermentation system of baker's yeast and deoxyriboaldolase-expressing Escherichia
      coli was investigated. In this process, baker's yeast generates fructose 1,6
      diphosphate from glucose and inorganic phosphate, and then the E. coli convert
      the fructose 1,6-diphosphate into 2-deoxyribose 5-phosphate via D-glyceraldehyde
      3-phosphate. Under the optimized conditions with toluene-treated yeast cells, 356
      mM (121 g/l) fructose 1,6-diphosphate was produced from 1,111 mM glucose and 750
      mM potassium phosphate buffer (pH 6.4) with a catalytic amount of AMP, and the
      reaction supernatant containing the fructose 1,6-diphosphate was used directly as
      substrate for 2-deoxyribose 5-phosphate production with the E. coli cells. With
      178 mM enzymatically prepared fructose 1,6-diphosphate and 400 mM acetaldehyde as
      substrates, 246 mM (52.6 g/l) 2-deoxyribose 5-phosphate was produced. The molar
      yield of 2-deoxyribose 5-phosphate as to glucose through the total two step
      reaction was 22.1%. The 2-deoxyribose 5-phosphate produced was converted to 2
      deoxyribose with a molar yield of 85% through endogenous or exogenous phosphatase
      activity.

PMID- 16794317
TI  - Production of alpha, omega-alkanediols using Escherichia coli expressing a
      cytochrome P450 from Acinetobacter sp. OC4.
AB  - Our biotransformation using Escherichia coli expressing a cytochrome P450 (CYP)
      belonging to the CYP153A family from Acinetobacter sp. OC4 produced a great
      amount of 1-octanol (2,250 mg per liter) from n-octane after 24 h of incubation.
      This level of production is equivalent to the maximum level previously achieved
      in biotransformation experiments of alkanes. In addition, the initial production
      rate of 1-octanol was maintained throughout the entire incubation period. These
      results indicate that we have achieved the functional and stable expression of a
      CYP in E. coli for the first time. Further, our biotransformation system showed
      alpha,omega-diterminal oxidation activity of n-alkanes, and a large amount of 1,8
      octanediol (722 mg per liter) was produced from 1-octanol after 24 h of
      incubation. This is the first report on the bioproduction of alpha,omega
      alkanediols from n-alkanes or 1-alkanols.

PMID- 16794319
TI  - A halophilic serine proteinase from Halobacillus sp. SR5-3 isolated from fish
      sauce: purification and characterization.
AB  - A halophilic bacterium was isolated from fish sauce, classified, and named
      Halobacillus sp. SR5-3. A purified 43-kDa proteinase produced by this bacterium
      showed optimal activity at 50 degrees C and pH 9-10 in 20% NaCl. The activity of
      the enzyme was enhanced about 2.5-fold by the addition of 20-35% NaCl, and the
      enzyme was highly stabilized by NaCl. It was found to be a serine proteinase
      related to either chymotrypsin or subtilisin. It absolutely preferred Ile at the
      P(2) position of substrates. Thus, the enzyme was found to be a halophilic serine
      proteinase with unique substrate specificity.

PMID- 16794318
TI  - Bioavailability of glucosyl hesperidin in rats.
AB  - Glucosyl hesperidin (G-hesperidin) is a water-soluble derivative of hesperidin.
      We compared the absorption and metabolism of G-hesperidin with those of
      hesperidin in rats. After oral administration of G-hesperidin or hesperidin to
      rats, hesperetin was detected in sera hydrolyzed with beta-glucuronidase, but it
      was not detectable in unhydrolyzed sera. Serum hesperetin was found more rapidly
      in rats administered G-hesperidin than in those administered hesperidin. The area
      under the concentration-time curve for hesperetin in the sera of rats
      administered G-hesperidin was approximately 3.7-fold greater than that of rats
      administered hesperidin. In the urine of both administration groups, hesperetin
      and its glucuronide were found. Urinary excretion of metabolites was higher in
      rats administered G-hesperidin than in those administered hesperidin. These
      results indicate that G-hesperidin presents the same metabolic profile as
      hesperidin. Moreover, it was concluded that G-hesperidin is absorbed more rapidly
      and efficiently than hesperidin, because of its high water solubility.

PMID- 16794320
TI  - Generation and characterization of monoclonal antibodies that specifically
      recognize p65/L-plastin isoform but not T-plastin isoform.
AB  - The 65-kDa protein (p65) was previously identified as a phosphorylated protein in
      activated macrophages, and has turned out to be a member of a plastin protein
      family characterized by a series of Ca(2+)-, calmodulin-, and beta-actin-binding
      domains. In mice, two isoforms, p65/L-plastin and T-plastin, have so far been
      identified; p65/L-plastin is expressed in hemopoietic cells and cancer cells, and
      T-plastin in solid tissue cells. We generated monoclonal antibodies to p65/L
      plastin, examined the isoform-specificity by using recombinant (r) T-plastin, and
      found that the antibodies were specific for rp65/L-plastin, whereas immune sera
      to rp65/L-plastin showed cross-reactions to rT-plastin. One of the antibodies,
      p65-7B5, was demonstrated to react to native p65/L-plastin by Western blot, flow
      cytometric, and immunohistochemical analysis. Furthermore, p65-7B5 has made it
      possible to detect p65/L-plastin-expressing cells in tissues where T-plastin is
      abundantly expressed. These reagents and procedures should provide specific tools
      to investigate the role of p65/L-plastin in leukocytes.

PMID- 16794321
TI  - Metabolic engineering of Saccharomyces cerevisiae producing nicotianamine:
      potential for industrial biosynthesis of a novel antihypertensive substrate.
AB  - Nicotianamine (NA), a metal chelator, is ubiquitous in higher plants. In humans,
      NA inhibits angiotensin I-converting enzyme (ACE), and consequently reduces high
      blood pressure. Nicotianamine is synthesized from the trimerization of S
      adenosylmethionine (SAM) by NA synthase (NAS). Here, we aimed to produce large
      amounts of NA fermentatively by introducing the Arabidopsis AtNAS2 gene into
      Saccharomyces cerevisiae strain SCY4. This strain can accumulate up to 100 times
      the usual amount of SAM, and this is considered desirable for overproduction of
      NA. Nicotianamine was produced in the engineered yeast, and the NA level
      increased with incubation time until the stationary phase. The maximum
      concentration of intracellular NA obtained was 766+/-33 microg/g wet weight.
      Successful production of NA in S. cerevisiae should pave the way for industrial
      production of this novel antihypertensive substrate.

PMID- 16794322
TI  - Difructose anhydride III does not contribute to body energy accumulation in rats.
AB  - We evaluated the body energy accumulation as fat and protein from ingestion of
      difructose anhydride III (DFAIII). Male Wistar rats were fed 0, 0.25, 0.5, 1.0,
      or 1.5 g per d of sucrose or DFAIII added to a 7 g of basal diet for 20 d.
      Supplements of DFAIII did not increase whole body or peripheral fat or total body
      energy, whereas sucrose increased them in a dose-dependent manner. Dose-dependent
      increases in body water were observed in both groups. The body protein was
      influenced by the dose of sugars. The estimated available energy value of DFAIII
      was 0.263 kcal per gram; this value is one-fifteenth that of sucrose. Ingestion
      of DFAIII dose-dependently increased the cecal SCFA pool. DFAIII was not detected
      in feces, showing complete degradation of DFAIII in the intestine. These results
      indicate that DFAIII is a fermentable saccharide with quite low available energy
      for fat accumulation.

PMID- 16794323
TI  - Polyphenolic constituent structures of Zanthoxylum piperitum fruit and the
      antibacterial effects of its polymeric procyanidin on methicillin-resistant
      Staphylococcus aureus.
AB  - Zanthoxylum piperitum (Rutaceae) is used as a spice and a natural medicine in
      Japan. Our study found that ZP-CT-A, a polymeric proanthocyanidin purified from
      the fruit of this species, noticeably decreased the minimum inhibitory
      concentrations of beta-lactam antibiotics for methicillin-resistant
      Staphylococcus aureus (MRSA). The structure of ZP-CT-A was characterized on the
      basis of (13)C NMR and size exclusion chromatographic data and the results of
      thiolytic degradation. A mechanistic study of the effects of ZP-CT-A indicated
      that it suppressed the activity of beta-lactamase and largely decreased the
      stability of the bacterial cell membrane of MRSA, as shown by a reduction in the
      tolerance of MRSA to low osmotic pressure and high ionic strength solutions.

PMID- 16794324
TI  - Hepatoprotective effects of purple potato extract against D-galactosamine-induced
      liver injury in rats.
AB  - We investigated the hepatoprotective effect of purple potato extract (PPE)
      against D-galactosamine (GalN)-induced liver injury in rats. PPE (400 mg) was
      administered once daily for 8 d, and then GalN (250 mg/kg of body weight) was
      injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha
      (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and
      asparate aminotranferase (AST) levels increased significantly after injection of
      GalN, but PPE inhibited GalN-induced alterations in serum TNF-alpha, LDH, ALT,
      and AST levels. Hepatic lipid peroxide and glutathione levels in the control +
      GalN group were higher and lower respectively than those in the control group,
      and those in the PPE + GalN group did not differ from that in the control group.
      The lipid peroxide level in hepatic microsomes treated with 2,2'-azobis (2
      amidinopropane) dihydrochloride in the PPE group was significantly lower than
      that in the control group. This suggests that PPE has hepatoprotective effects
      against GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or
      inflammation in rats.

PMID- 16794325
TI  - Chicken ovalbumin promoter is demethylated upon expression in the regions
      specifically involved in estrogen-responsiveness.
AB  - Here we report the methylation status of the chicken ovalbumin promoter. Genomic
      DNA of oviduct from immature chickens and laying hens was analyzed through
      bisulfite genomic sequencing. In the ovalbumin control locus up to the 6 kb
      upstream region, CpG sites were methylated in immature chickens, except for
      several sites, and almost all CpGs residing in DNase I hypersensitive sites I,
      II, and III, but not IV, were selectively unmethylated in ovalbumin expressing
      chickens. Chromatin immunoprecipitation assays showed that the ovalbumin control
      region was associated with acetylated histone H3 but not with dimethylated
      histone H3 at Lys 27. These results demonstrate that DNA demethylation was
      restricted to short DNA regions of DNase I hypersensitive sites, especially to
      those which participated in estrogen-responsiveness, even when cells expressed
      extremely high levels of ovalbumin and these sites were associated with
      acetylated histones.

PMID- 16794326
TI  - Salicylic acid-mediated cell death in the Arabidopsis len3 mutant.
AB  - The Arabidopsis lesion initiation 3 (len3) mutant develops lesions on leaves
      without pathogen attack. len3 plants exhibit stunted growth, constitutively
      express pathogenesis-related (PR) genes, PR-1, PR-2, and PR-5, and accumulate
      elevated levels of salicylic acid (SA). Furthermore, len3 is a semidominant, male
      gametophytic lethal mutation with partial defects in female gametophytic
      development. To determine the signaling pathway activated in len3 plants, we
      crossed the len3 plants with nahG, npr1-1, and pad4-1 plants and analyzed the
      phenotypes of the double mutants. The len3-conferred phenotypes, including cell
      death and PR-1 expressions, were suppressed in the double mutants. Thus SA, NPR1,
      and PAD4 are required for the phenotypes. However, none of these double mutants
      could completely suppress the len3-conferred stunted growth. This result suggests
      that an SA-, NPR1-, and PAD4-independent pathway is also involved in the
      phenotype. Treatment with BTH (benzo(1,2,3)thiadiazole-7-carbothioic acid), an SA
      analog, induced cell death in len3 nahG plants but not in len3 npr1 or len3 pad4
      plants, suggesting the involvement of the PAD4-dependent but SA-independent
      second signal pathway in cell death in len3 plants.

PMID- 16794327
TI  - Characterization of flavonoid 7-O-glucosyltransferase from Arabidopsis thaliana.
AB  - Most flavonoids found in plants exist as glycosides, and glycosylation status has
      a wide range of effects on flavonoid solubility, stability, and bioavailability.
      Glycosylation of flavonoids is mediated by Family 1 glycosyltransferases (UGTs),
      which use UDP-sugars, such as UDP-glucose, as the glycosyl donor. AtGT-2, a UGT
      from Arabidopsis thaliana, was cloned and expressed in Escherichia coli as a
      gluthatione S-transferase fusion protein. Several compounds, including
      flavonoids, were tested as potential substrates. HPLC analysis of the reaction
      products indicated that AtGT-2 transfers a glucose molecule into several
      different kinds of flavonoids, eriodictyol being the most effective substrate,
      followed by luteolin, kaempferol, and quercetin. Based on comparison of HPLC
      retention times with authentic flavonoid 7-O-glucosides and nuclear magnetic
      resonance spectroscopy, the glycosylation position in the reacted flavonoids was
      determined to be the C-7 hydroxyl group. These results indicate that AtGT-2
      encodes a flavonoid 7-O-glucosyltransferase.

PMID- 16794329
TI  - Inhibitory effects of pasuchaca (Geranium dielsiaum) extract on alpha-glucosidase
      in mouse.
AB  - The methanolic extract of pasuchaca (Geranium dielsiaum) (PsEx) was found to
      suppress blood glucose elevation after oral administration of sucrose, maltose,
      and starch, but not after oral administration of glucose, in the mouse. In vitro
      examination of the inhibitory effect of PsEx on maltase activity revealed that
      PsEx strongly inhibited mouse small intestine maltase activity. Taken together,
      these results suggest that the inhibitory effect of PsEx on alpha-glucosidase
      activity might contribute to delay in carbohydrate digestion and subsequent
      lowering of the blood glucose level, thereby leading to prevention and cure of
      diabetes.

PMID- 16794328
TI  - Characterization and analysis of sesamolinol diglucoside in sesame seeds.
AB  - A new lignan glucoside was isolated from defatted sesame seed flour and its
      structure was established as sesamolinol diglucoside [2-(3-methoxy-4-(O-beta-D
      glucopyranosyl (1-->6)-O-beta-D-glucopyranoside)phenoxyl)-6-(3,4
      methylenedioxyphenyl)-cis-3,7-dioxabicyclo-(3.3.0)-octane] by mass and nuclear
      magnetic resonance spectroscopy. A quantitative analysis of 65 sesame seed
      samples showed that this sesamolinol diglucoside ranged from <5 to 232 mg/100 g
      of seeds (98+/-57 mg/100 g) with no difference between white and black sesame
      seeds.

PMID- 16794330
TI  - Enhancement by lactosucrose of the calcium absorption from the intestine in
      growing rats.
AB  - The effects of dietary lactosucrose on calcium absorption from the intestine and
      calcium accumulation in bones were investigated in growing female rats. The
      apparent calcium-45 ((45)Ca) absorption, residual (45)Ca ratio in the body, and
      (45)Ca accumulation in the femur and tibia of lactosucrose-supplemented rats were
      significantly higher than in control rats 24 h after the administration of a
      (45)CaCl(2) solution.

PMID- 16794331
TI  - Antioxidative activity of bound-form phenolics in potato peel.
AB  - Free and bound-form phenolics were isolated from potato (cv. Toyoshiro) flesh and
      peel. The free and bound-form phenolics in the peel showed high DPPH radical
      scavenging activity, while those in the flesh showed low activity. The total
      amount of chlorogenic acid and caffeic acid in the free-form phenolics from the
      peel was highly correlated with the DPPH radical scavenging activity. Ferulic
      acid was identified as the active radical scavenging compound in the bound-form
      phenolics from the peel. The potato peel may therefore offer an effective source
      of an antioxidative.

PMID- 16794332
TI  - Identification of cis-acting regions that contribute to neuron-specific
      expression of the GAP-43 gene.
AB  - There are two transcription start sites in the growth-associated protein 43 (GAP
      43) promoter, and several repressive elements have been reported in the control
      region. But the repressive effects have been analyzed only for the distal
      transcription start site. Among the repressive elements reported, we found that
      modulator I repressed GAP-43 gene expression from the proximal promoter in non
      neuronal cells. We also found a novel stimulative element immediately downstream
      of modulator I.

PMID- 16794333
TI  - Isolation and identification of 5-methyl-imidazolin-4-one derivative as
      glyceraldehyde-derived advanced glycation end product.
AB  - We isolated and identified the glyceraldehyde-derived advanced glycation product
      (AGE) formed from glyceraldehyde and N(alpha)-acetylarginine. A major product was
      identified as N(alpha)-acetyl-N(delta)-(5-methyl-imidazolin-4-one-2-yl)
      ornithine. The compound has been reported as methylglyoxal-derived AGE, MG-H1.
      This study suggests that MG-H1 is formed through both glyceraldehyde-related and
      methylglyoxal-related pathways. There is a possibility that MG-H1 becomes an
      index of injury to glyceraldehyde and methylglyoxal-related enzymes.

PMID- 16794334
TI  - Stimulation of melanogenesis by the citrus flavonoid naringenin in mouse B16
      melanoma cells.
AB  - Naringenin is a naturally occurring citrus flavanone. In this study, we examined
      the effect of naringenin on melanogenesis in mouse B16 melanoma cells. Melanin
      contents and tyrosinase activities were strongly increased by naringenin.
      Naringenin was found to cause marked increases in the expression levels of
      melanogenic enzymes.

PMID- 16794335
TI  - Repraesentins D, E and F, new plant growth promoters from Lactarius
      repraesentaneus.
AB  - Three new plant growth regulatory sesquiterpenes were isolated from the Lactarius
      repraesentaneus fungus. Their structures were elucidated to be lactarane
      sesquiterpenes, namely repraesentins D (1) and E (2), and a protoilludane-related
      sesquiterpene, namely repraesentin F (3). Repraesentin E (2) showed the strongest
      promotion activity, 164% at 3.6 microM, of the three compounds toward the radicle
      elongation of lettuce seedlings.

PMID- 16794336
TI  - A skin color mutation of grapevine, from black-skinned Pinot Noir to white
      skinned Pinot Blanc, is caused by deletion of the functional VvmybA1 allele.
AB  - A white-wine grape, Pinot Blanc, is thought to be a white-skinned mutant of a red
      wine grape, Pinot Noir. Pinot Noir was heterozygous for VvmybA1. One allele was
      the non-functional VvmybA1a, and the other was the functional VvmybA1c. In Pinot
      Blanc, however, only VvmybA1a was observed, and the amount of VvmybA1 DNA in
      Pinot Blanc was half that in Pinot Noir. These findings suggest that deletion of
      VvmybA1c from Pinot Noir resulted in Pinot Blanc.

PMID- 16794337
TI  - Characterization of arylsulfatase formed by derepressed synthesis in Citrobacter
      braakii.
AB  - Arylsulfatase activity was detected in a bacterial strain, Citrobacter braakii 69
      b, isolated from soil by enrichment cultivation using porcine gastric mucin. The
      production of arylsulfatase was derepressed markedly in a synthetic medium by the
      addition of tyramine. The purified enzyme hydrolyzed 4-nitrophenyl sulfate, 4
      nitrocatechol sulfate, and 3-indoxyl sulfate, and was classified as type I
      arylsulfatase.

PMID- 16794338
TI  - Capsinoid is biosynthesized from phenylalanine and valine in a non-pungent
      pepper, Capsicum annuum L. cv. CH-19 sweet.
AB  - The biosynthetic pathway of capsinoid in 'CH-19 Sweet' was investigated.
      [(3)H]Valine and [(14)C]phenylalanine were injected into the fruits of the intact
      plant. Both of radioactivities were detected in capsinoid fractions. (14)C
      radioactivity was observed in phenylpropanoid compounds, and in vanillin,
      vanillylamine, vanillyl alcohol, and vanillic acid. We confirmed that capsinoid
      is biosynthesized from phenylalanine and valine.

PMID- 16794339
TI  - Effect of ascorbic acid on the chemiluminescence of polyphenols.
AB  - The chemiluminescence of gallic acid by hydrogen peroxide had completely
      inhibited by the presence of ascorbate. After ascorbate had disappeared by
      oxidation, chemiluminescence returned. The concentration of gallic acid was
      virtually unchanged by presence of ascorbate, but started to decrease after the
      disappearance of ascorbate. This might be attributable to the rapid reduction of
      quinone, which was the first product of the chemiluminescence reactions, to
      gallic acid by ascorbate or the donation of proton to the phenoxy radical from
      ascorbate to stop the chemiluminescence reaction at the first stage. The effects
      of ascorbate on the chemiluminescence of other polyphenols depended on their
      oxidation rate.

PMID- 16794340
TI  - Repression of secondary metabolite production by exogenous cAMP in Monascus.
AB  - The cAMP signal pathway controls various biological functions, including
      secondary metabolism of filamentous fungi. We found that exogenous cAMP represses
      the production of lovastatin, red pigments, and citrinin in Monascus.
      Interestingly, a mutant MK-1 with increased lovastatin and red pigments
      production was not influenced by cAMP on these productions, indicating that cAMP
      signaling might be lacking in MK-1.

PMID- 16794341
TI  - Recombinant, rice-produced yeast phytase shows the ability to hydrolyze phytate
      derived from seed-based feed, and extreme stability during ensilage treatment.
AB  - When fresh rice leaves producing yeast Schwanniomyces occidentalis phytase were
      grounded and mixed with the whole extract of seed-based feed for pigs, the
      release of orthophosphate increased significantly. More specifically, phytate, a
      major source of phosphorus in the seeds, was hydrolyzed by heterologous phytase.
      Moreover, when transgenic rice plants were ensiled for up to 12 weeks, no
      decrease in the phytase activity of the heterologous enzyme was observed. This
      result strongly suggests that transgenic rice plants producing yeast phytase can
      be stored as silage without any loss of enzyme activity until usage as a feed
      additive.

PMID- 16794342
TI  - Stereoselective incorporation of isoleucine into Cypridina luciferin in Cypridina
      hilgendorfii (Vargula hilgendorfii).
AB  - The emission of light in the marine ostracod Cypridina hilgendorfii (presently
      Vargula hilgendorfii) is produced by the Cypridina luciferin-luciferase reaction
      in the presence of molecular oxygen. Cypridina luciferin has an asymmetric carbon
      derived from isoleucine, and the absolute configuration is identical to the C-3
      position in L-isoleucine or D-alloisoleucine. To determine the stereoselective
      incorporation of the isoleucine isomers (L-isoleucine, D-isoleucine, L
      alloisoleucine, and D-alloisoleucine), we synthesized four (2)H-labeled
      isoleucine isomers and examined their incorporation into Cypridina luciferin by
      feeding experiments. Judging by these results, L-isoleucine is predominantly
      incorporated into Cypridina luciferin. This suggests that the isoleucine unit of
      Cypridina luciferin is derived from L-isoleucine, but not from D-alloisoleucine.

PMID- 16794343
TI  - Possible involvement of calcium signaling pathways in L-leucine-stimulated
      protein synthesis in L6 myotubes.
AB  - L-Leucine is known to stimulate protein synthesis in L6 myotubes. In the present
      study, we examined the possible involvement of calcium signaling pathways in the
      stimulation of protein synthesis induced by L-leucine in L6 myotubes. After 16 h
      of treatment with L-leucine-depleted medium, the re-addition of L-leucine for 4 h
      augmented protein synthesis by about 50% as compared with an L-leucine-depleted
      control. Ryanodine receptor antagonists almost completely abolished the
      stimulatory effect of L-leucine, while IP(3) receptor antagonists showed partial
      inhibition when added simultaneously with L-leucine. These results suggest the
      possibility that calcium signaling pathways are involved in L-leucine-stimulated
      protein synthesis.

PMID- 16794344
TI  - Optimum substrate size and specific anomer requirements for the reducing-end
      glycoside hydrolase di-N-acetylchitobiase.
AB  - Di-N-acetylchitobiase is a family 18 glycoside hydrolase that splits the reducing
      end GlcNAc from chitooligosaccharides. The enzyme hydrolyzed only the alpha
      anomer of five tested substrates, chitin di- through hexasaccharide. In all cases
      the glycosyl fragment retained its beta-configuration while the split
      monosaccharide was alpha-D-GlcNAc. Chitobiose was hydrolyzed less than half as
      fast as the other larger substrates. All four of them, tri- to hexasaccharide,
      reacted at the same rate. The biochemical behavior of di-N-acetylchitobiase
      indicates it has three subsites, -2, -1, +1, in which the reducing-end trimer of
      any sized chitooligosaccharide is bound. The +1 site is specific for an alpha
      anomer.

PMID- 16794345
TI  - Client binding of Cdc37 is regulated intramolecularly and intermolecularly.
AB  - Recently we showed that the glycine-rich loop in the N-terminal portion of
      protein kinases and the client-binding site of Cdc37 are both necessary for
      interaction between Cdc37 and protein kinases. We demonstrate here that the N
      terminal portion of Cdc37, distinct from its client-binding site, interacts with
      the C-terminal portion of Raf-1. This interaction might expose the client-binding
      site of Cdc37. In addition, we provide evidence indicating that Cdc37 is
      monomeric in its physiological state, and that it becomes a dimer only when it is
      complexed with both Hsp90 and protein kinases.

PMID- 16794346
TI  - Histological effects of intraputaminal infusion of glial cell line-derived
      neurotrophic factor in Parkinson disease model macaque monkeys.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a potent neuroprotection
      and regeneration molecule for dopamine neurons in the substantia nigra. A recent
      clinical study showed that intraputaminal infusions of GDNF restored the striatal
      dopaminergic function, resulting in improvement in patients with Parkinson
      disease. To investigate the efficacy and the safety of this treatment, the
      histological changes associated with intraputaminal GDNF infusions were
      investigated in non-human primate models of Parkinson disease. Two types of
      Parkinson disease model were constructed: unilateral infusion of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridin (MPTP) into the internal carotid artery to
      induce hemiparkinsonism and intermittent systemic injection to induce Parkinson
      disease. GDNF (50 microg) was infused into the putamen on the day of the first
      MPTP treatment and 4 weeks later. The monkey brains were examined by
      immunohistochemistry 2-4 weeks after the second GDNF infusion. Losses of the
      nigral dopamine neurons were mild (30-50% loss) on the side of GDNF infusion, and
      moderate (approximately 70% loss) on the side of vehicle infusion in the
      Parkinson disease model. The dopamine fibers were thick and dense in the striatum
      around the GDNF infusion sites. Both GDNF- and vehicle-treated monkeys of the
      hemiparkinsonian model showed severe decrease of dopamine neurons to 10% of the
      intact side. Although reactive astrocytes proliferated around the GDNF infusion
      sites, the densities of striatal neurons involving GABAergic and cholinergic
      neurons were not affected. Intraputaminal infusions of GDNF have beneficial
      effects in parkinsonian monkeys, but dose control is required according to the
      severity of the disease. The specificity for dopamine neurons is quite high and
      there are no serious histological changes.

PMID- 16794347
TI  - Perimesencephalic nonaneurysmal subarachnoid hemorrhage caused by physical
      exertion.
AB  - The clinical characteristics of perimesencephalic nonaneurysmal subarachnoid
      hemorrhage (SAH) caused by physical exertion were analyzed to investigate the
      causes and mechanisms of perimesencephalic nonaneurysmal SAH. Nine of 209
      patients with spontaneous SAH were identified as having perimesencephalic
      nonaneurysmal SAH. Perimesencephalic nonaneurysmal SAH in four males and three
      females was precipitated by exertion. Age, sex predominance, type of exertion,
      symptoms, loss of consciousness during bleeding, clinical grade, angiographic
      spasm, hydrocephalus, delayed ischemic deficit, rebleeding, hypertension, and
      outcome were evaluated in these seven patients. Outcomes were assessed using the
      Glasgow Outcome Scale. Patients showed male predominance (57.1%), relatively
      young age (mean 50 years), low frequency of hypertension (28.6%), good clinical
      grade (World Federation of Neurological Surgeons grade I or II), and excellent
      outcomes including no rebleeding, no symptomatic hydrocephalus, and no delayed
      ischemic deficits. The type of exertion was swimming in two patients, golfing in
      two patients, heavy lifting in two patients, and bending forward during
      gymnastics in one patient. Physical exertion including components of the Valsalva
      maneuver is an important predisposing factor for perimesencephalic nonaneurysmal
      SAH. Such physical exertion produces increased intrathoracic pressure, which
      blocks the internal jugular venous return, resulting in elevated intracranial
      venous pressure or mechanical swelling of the intracranial veins, and leads to
      venous or capillary breakdown.

PMID- 16794348
TI  - Stepwise revascularization for prevention of postoperative hyperperfusion.
AB  - Abrupt normalization of cerebral blood flow (CBF) after surgical procedures to
      improve excessive cerebral hypoperfusion can cause irreversible brain parenchymal
      damage. Such hyperperfusion, which is caused by inflow at normal blood pressure
      into maximally dilated fine vessels, is an important complication following
      carotid endarterectomy (CEA). Strict control of blood pressure in the
      perioperative period can prevent this complication except in a few patients, who
      have severe cerebral hypoperfusion and poor cerebrovascular reserve due to
      extremely severe stenosis of the ipsilateral or the bilateral carotid arteries,
      for which CEA is indicated. The requirement for improved CBF and the risk of
      postoperative hyperperfusion conflict in the pathogenesis of these patients. We
      tried to prevent abrupt improvement in perfusion by attempting gradual
      restoration of CBF. Superficial temporal artery-middle cerebral artery
      anastomosis was first performed to improve the poor cerebrovascular reserve by
      allowing insufficient blood flow. A few weeks later, CEA was performed to
      completely restore CBF. This surgical approach obtained good results without
      postoperative problems in four patients. The indications of this surgical
      management and efficacy of stepwise restoration of CBF to prevent postoperative
      hyperperfusion depend on careful preoperative evaluation of perfusion studies.

PMID- 16794349
TI  - External carotid artery aneurysm developing after embolization of a ruptured
      posterior inferior cerebellar artery aneurysm in a patient with cervicocephalic
      fibromuscular dysplasia--case report.
AB  - A 30-year-old man presented with an aneurysm of the left posterior inferior
      cerebellar artery manifesting as subarachnoid hemorrhage and cerebellar
      infarction. Angiography demonstrated string-of-beads sign typical of
      fibromuscular dysplasia (FMD) in the extracranial carotid and vertebral arteries.
      The aneurysm and the parent artery were successfully embolized with Guglielmi
      detachable coils. Severe vasospasm developed 1 week after admission, and was
      treated several times by selective injection of vasodilator. A new aneurysm of
      the left external carotid artery became evident 1 month later, whereas only
      slight dilation had previously been apparent. This angiographic sequence
      demonstrated a new arterial dissection. Despite the possibility of damage to the
      artery during multiple catheterizations, arterial wall changes caused by FMD
      appear to have been primarily responsible. This case emphasizes the need for
      particular care in performing vascular interventional procedures in the presence
      of FMD.

PMID- 16794351
TI  - Intradural C-1 ventral root schwannomas treated by surgical resection via the
      lateral suboccipital transcondylar approach--three case reports.
AB  - Three female patients aged 50-79 years (mean 61.0 years) presented with extremely
      rare intradural C-1 root schwannoma manifesting as foramen magnum syndrome.
      Magnetic resonance imaging revealed the intradural extra-axial tumors extending
      from the anterior aspect of the medullospinal junction, with a mean major
      diameter of 2.7 cm. Total resection of the tumors was performed via the lateral
      suboccipital transcondylar approach after a mean period of 11.7 months from the
      symptom onset. The final diagnosis of schwannoma of the C-1 ventral root was
      based on the intraoperative and histological findings. All three patients were
      successfully rehabilitated, with symptomatic improvement and no evidence of tumor
      recurrence. All three patients were successfully treated by surgical resection
      via the lateral suboccipital transcondylar approach. This approach is effective
      and safe provided individual anatomy, drilling of the occipital condyle, and
      patient position are considered carefully.

PMID- 16794350
TI  - Parasagittal leptomeningeal hemangioblastoma--case report.
AB  - A 50-year-old male patient presented with a rare dural supratentorial
      hemangioblastoma manifesting as severe headache persisting for 2 months.
      Neuroimaging revealed a tumoral mass localized in the right parietal lobe near
      the sagittal sinus. The tumor was totally excised successfully. The postoperative
      histological diagnosis was hemangioblastoma. Such supratentorial
      hemangioblastomas can easily be removed because of the arachnoid cleavage plane.

PMID- 16794352
TI  - Thyroid follicular carcinoma metastasized to the lung, skull, and brain 12 years
      after initial treatment for thyroid gland--case report.
AB  - A 65-year-old woman presented with multiple metastases from thyroid follicular
      carcinoma to the lung, skull, and brain. The skull and brain tumors had been
      successfully treated by surgery, thyroxine supplementation, and radiosurgery
      until she died of sudden intracerebral hemorrhage which had no connection with
      tumor treatment. The lung tumor was treated by conventional irradiation and
      radioactive ablation. Well-differentiated thyroid carcinoma is a slowly
      progressive tumor. Follicular carcinoma is thought to have the most optimistic
      prognosis even with metastases to the lymph nodes and lung. Radioactive ablation
      using iodine-131 is widely used to treat the primary and/or metastatic lesion.
      However, the prognosis for patients with brain metastases is poor. Intracranial
      metastasis of this tumor is rare, but has a mean posttreatment survival of around
      12 months. Surgical excision of the metastatic intracranial lesion may be the
      only effective treatment.

PMID- 16794353
TI  - Neuronavigation-assisted transoral-transpharyngeal approach for basilar
      invagination--two case reports.
AB  - Two patients presented with congenital basilar invagination manifesting as
      progressive myelopathy. Both patients underwent surgery using a neuronavigation
      assisted transoral-transpharyngeal approach. The Brain-LAB Vector Vision
      navigation system was used for image guidance. The registration accuracies were
      0.9 and 1.3 mm. After decompression, posterior stabilization was performed. Both
      patients had an uneventful postoperative course. The transoral-transpharyngeal
      approach with the neuronavigation system provides safe exposure and decompression
      for basilar invagination.

PMID- 16794354
TI  - Spinal arachnoid cyst causing paraplegia following skull base surgery.
AB  - A 40-year-old woman presented with a right petroclival meningioma compressing the
      brainstem and manifesting as a 6-month history of headache and gait difficulty.
      The patient underwent subtotal removal of the tumor via an anterior transpetrosal
      approach. The postoperative course was complicated by cerebrospinal fluid
      rhinorrhea, bacterial meningitis, and acute hemorrhagic rectal ulcer. The patient
      was discharged home in good condition after prolonged medical treatment. Four
      months after the surgery, the patient noted recurrence of gait difficulty.
      Magnetic resonance (MR) imaging of the brain showed enlargement of the ventricles
      and no residual brainstem compression. A ventriculoperitoneal shunt was placed,
      but the symptoms were unchanged. The shunt was removed 2 months later because of
      infection. The patient's gait gradually deteriorated, although repeat brain MR
      imaging showed no significant increase in ventricular size. Ten months after the
      initial surgery she became paraplegic. MR imaging of the thoracic spine revealed
      a large arachnoid cyst extending from C-6 to T-6. The patient underwent T2-4
      laminectomy, partial removal of the cyst wall, and duraplasty, but no clinical
      improvement was observed. Preexisting long-tract signs and coincidental
      hydrocephalus confused the neurological findings and delayed detection of the
      spinal lesion in this case. Neurosurgeons should be alert to the possibilities of
      insidious spinal lesion if the patient has progressive neurological disorder
      which does not match the known cranial lesion.

PMID- 16794355
TI  - Surgical treatment of congenital kyphosis associated with progressive spastic
      paralysis in an adult patient.
AB  - A 38-year-old man presented with untreated congenital kyphosis associated with
      progressive spastic gait. To prevent progression of the spastic paralysis, rigid
      correction of the severe spinal deformity arising from the congenital kyphosis
      was performed by one-stage posterior closing-wedge osteotomy, without occurrence
      of neurological complications. Progression of the paralysis has not been
      identified for 30 months after the operation and a slight improvement in gait was
      recognized. The current case is categorized as type I deformity of congenital
      kyphosis in the upper thoracic spine, which is normally treated surgically before
      the adolescent growth phase begins.

PMID- 16794356
TI  - Supplementary comment on "optimal extent of resection in vestibular schwannoma
      surgery: relationship to recurrence and facial nerve preservation".

PMID- 16794357
TI  - Supplementary comment on "analysis of risk factors for infection in coplacement
      of percutaneous endoscopic gastrostomy and ventriculoperitoneal shunt".

PMID- 16794358
TI  - IGF-I and epidermal growth factor levels in follicular fluid of women undergoing
      controlled ovarian hyperstimulation using the multidose GnRH-antagonist protocol
      or the long GnRH-agonist protocol.
AB  - The intrafollicular levels of IGF-I and epidermal growth factor (EGF) were
      studied in women undergoing controlled ovarian hyperstimulation using the
      multidose GnRH-antagonist protocol or the long agonist protocol, in an attempt to
      elucidate whether GnRH-antagonists affect the levels of the two growth factors.
      The follicular fluid concentration of IGF-I, EGF, estradiol and progesterone were
      detected in 68 women undergoing ovarian hyperstimulation for intracytoplasmic
      sperm injection (ICSI) cycles. There were no differences in intrafollicular
      concentrations of EGF and IGF-I in the two studied groups. Additionally, we found
      no correlation between the intrafollicular levels of IGF-I or EGF and the ICSI
      outcome. The intrafollicular levels of IGF-I were positively correlated with
      those of progesterone. In conclusion, the intrafollicular levels of IGF-I and EGF
      do not seem to be influenced by the stimulation protocol. The intrafollicular
      levels of both growth factors can not serve as prognostic markers for the ICSI
      outcome.

PMID- 16794359
TI  - Currently available somatostatin analogs are not good for Graves' orbitopathy.

PMID- 16794360
TI  - Growth Hormone Registry: A step forward in standard diagnostic practices in
      Italy.

PMID- 16794361
TI  - Dehydroepiandrosterone and human adipose tissue.
AB  - OBJECTIVE: The aim of this study was to investigate whether DHEA alters the
      proliferation and differentiation of human sc and visceral adipose cells in
      primary cultures. METHOD: Sc and omental adipose tissue was obtained from 10
      female donors aged 36+/-3.6 yr with a body mass index (BMI) of 33+/-3.21 kg/m2.
      Stromal vascular cells were isolated and cultured using modified procedures
      described by Entenmann and Hauner. For the proliferation assay, stromal-vascular
      cells from sc and visceral adipose tissue cultures were fed with proliferation
      media containing 0, 25 or 100 microM DHEA for 3 days. At the end of this
      treatment period, two type cultures were prepared for determining their metabolic
      activity using the sulforhodamine B staining procedure. RESULTS: The metabolic
      activity of proliferating human visceral adipose tissue was higher than sc
      adipose tissue. The activity of proliferating human visceral tissue cultures
      decreased more than the sc tissue as the level of DHEA in the cultures was
      increased. CONCLUSIONS: These data suggest that DHEA predominantly influences the
      proliferation and differentiation of human omental adipose tissue.

PMID- 16794362
TI  - Growth hormone replacement therapy in growth hormone deficient children and
      adults: Effects on hemochrome.
AB  - Several lines of evidence have suggested a role of the GH/IGF-I axis in the
      regulation of hemochrome. Many studies have been carried out in GH deficient
      children and adults about this topic, reporting predominantly a positive effect
      of recombinant human GH (rhGH) on red series, with no action on serum leucocytes
      and platelets counts. The aim of this study was to assess the impact of GH
      deficiency (GHD) and of rhGH replacement on blood cells count in 17 pre-pubertal
      children with idiopathic isolated GHD (11 males and 6 females, aged 9.1+/-0.8 yr)
      and in 18 patients with adult-onset GHD (12 males and 6 females, aged 47.9+/-3.0
      yr). Evaluation of absolute and SD score (SDS) values of red blood cells,
      hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin,
      mean corpuscular hemoglobin concentration, platelets and white blood cells was
      performed at baseline and after 12 months of rhGH treatment (0.045+/-0.001 mg/kg
      bw/day and 4.2+/-0.5 microg/kg bw/day for children and adults, respectively). At
      baseline, all patients showed low IGF-I levels. Effectiveness of rhGH therapy was
      documented by significant increase in height SDS, height velocity and serum IGF-I
      levels in children. In adults, adequacy of rhGH was demonstrated by significant
      increase in serum IGF-I and significant decrease in body fat. At baseline, about
      25% of patients (4 of 17 children and 4 of 18 adults) showed normochromic
      normocytic anemia, while the other indices were normal. In 7 of the 8 anemic
      patients, normal levels of hemoglobin were restored on rhGH, while no change in
      all the other indices was observed. In conclusion, rhGH therapy at physiological
      doses has no effect on erythropoiesis in GHD children and adults with normal
      blood cells count, while in patients with normochromic normocytic anemia rhGH is
      able to restore normal hemoglobin levels.

PMID- 16794363
TI  - An empowerment-based educational program improves psychological well-being and
      health-related quality of life in Type 1 diabetes.
AB  - Educational programs are reported to improve metabolic control and well-being in
      Type 1 diabetes mellitus (DM), but the effects of newly- structured
      interventions, aimed at promoting empowerment in educated patients in active
      selfcare, have received little attention. Ninety patients with Type 1 DM in
      intensive insulin treatment were invited to an empowerment-based educational
      intervention. Changes in quality of life and psychological well-being in the 54
      patients participating in the program (median age, 44 yr) were compared with
      those measured in patients who refused. The following questionnaires were
      administered at baseline and 12 months later: Psychological General Well-Being
      (PGWB), Medical Outcome Survey Short-Form 36 (SF-36), and Well-Being Enquiry for
      Diabetics (WED). Baseline values were indicative of moderate, but significant,
      psychological distress in the whole cohort. At follow-up, the experimental group
      had a better metabolic control {glycosylated hemoglobin, -0.4% [time x treatment
      analysis of variance (ANOVA), p = 0.005 vs controls]}, and a general improvement
      in comprehensive indices and most scales of PGWB and SF-36. Vitality (p = 0.042)
      and Social Functioning (p = 0.039) were no longer different from population norm.
      Similarly, the Symptoms (p = 0.005), Discomfort (p = 0.043) and Impact scales (p
      = 0.032) of WED, reflecting physical functioning, diabetes-related worries and
      familial relationships, role functioning and social network, improved
      significantly in treated patients. An educational empowerment-based intervention
      significantly improves the psychosocial aspects of diabetes and quality of life
      also in patients in active and effective self-care. Repeated educational
      interventions are the way towards a normal life with Type 1 DM.

PMID- 16794364
TI  - Slow-release lanreotide in Graves' ophthalmopathy: A double-blind randomized,
      placebo-controlled clinical trial.
AB  - SS analogs are an attractive alternative in treating Graves' ophthalmopathy (GO).
      Most of the previous studies were uncontrolled and enrolled few patients. The
      present study was conducted as a larger scale, prospective, randomized controlled
      study to determine the effectiveness of a slow-release formulation of lanreotide
      in GO. Sixty patients with active GO received an im injection every two weeks of
      either lanreotide 30 mg or placebo for 12 weeks. They were then followed and
      further treated in the traditional way if necessary. The Clinical Activity Score
      (CAS) was the primary efficacy criterion. Proptosis, diplopia, corneal erosion or
      ulcer, visual acuity, extraocular muscle movement and intraocular pressure were
      also evaluated. At the end of the 12 weeks, the mean CAS was not significantly
      decreased in the lanreotide group compared to the placebo group. The overall mean
      difference of proptosis between these two groups also did not reach significance
      at 12 weeks. Only diplopia at downward gaze had significant improvement for the
      lanreotide- treated group vs placebo group (p = 0.03). No differences were
      observed between the two groups compared to other outcome measures. During the 24
      month follow-up after the clinical trial, 14 patients received eye surgery in the
      placebo group compared with 10 patients in the lanreotide group (p = 0.29). Six
      patients received methylprednisolone pulse therapy in the placebo group and two
      patients in the lanreotide group (p = 0.25). In conclusion, lanreotide treatment
      had no significant effects on GO compared with placebo.

PMID- 16794365
TI  - The newly developed three-dimensional (3D) and two-dimensional (2D) thyroid
      ultrasound are strongly correlated, but 2D overestimates thyroid volume in the
      presence of nodules.
AB  - The newly developed three-dimensional (3D) and two-dimensional (2D) thyroid
      ultrasound (US) were compared in assessing thyroid volume (TV) in 104 patients:
      53 had an isolated thyroid nodule, 32 toxic diffuse goiter, 17 non-toxic
      multinodular goiter, 1 toxic multinodular goiter and 1 a toxic adenoma. A real
      time Technos apparatus (Esaote SpA, Italy) with a 7,5 MHz linear transducer was
      used. The volume of thyroid lobes by 2D was calculated according to the ellipsoid
      formula. In the same session, TV by 3D US was calculated using a probe tracking
      system (in vivo ScanNT Esaote 3.4 MedCom. Darmasdt) and software to reconstruct
      3D images, directly giving the lobe volume. There was a very good agreement
      between 2D and 3D, but in 94/208 lobes with nodular lesions 2D showed a 10%
      systematic overestimation compared to 3D, the percentage error being higher in
      lobes with lower volumes. A possible explanation for this result is the
      inadequacy of the ellipsoid formula in forecasting the correct lobe profile in
      the presence of nodules. This intrinsic defect of 2D US should be taken into
      account when evaluating TV in patients with nodular goiter.

PMID- 16794366
TI  - Value of routine measurement of serum calcitonin concentrations in patients with
      nodular thyroid disease: A multicenter study.
AB  - BACKGROUND: The routine measurement of serum calcitonin (CT) has been proposed
      for patients with nodular thyroid disease (NTD), to detect unsuspected medullary
      thyroid carcinoma (MTC) before surgery. OBJECTIVE: To assess the prevalence of
      hypercalcitoninemia and MTC in NTD patients; to compare the ability of CT
      measurement and fine needle aspiration cytology (FNAC) to predict MTC; to
      identify age groups of NTD patients who should be better candidates than others
      to undergo routine measurement of CT. PATIENTS AND METHODS: 1425 consecutive
      patients, referred from April 1, 2003, through March 31, 2004, to four Italian
      endocrine centers due to NTD, were grouped depending on age, and underwent basal
      and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when
      indicated, surgery. Serum CT concentrations were measured by an
      immunoluminometric assay (ILMA). RESULTS: Hypercalcitoninemia was found in 23 out
      of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing
      high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before
      surgery was 100% for both tests, whereas specificity was 95 and 93%,
      respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was
      taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were
      considered, FNAC sensitivity approached 100%. On the contrary, a correct
      cytological diagnosis was obtained in only one out of five patients with <10 mm
      MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC
      even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated
      with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia
      was found in 57% of hypercalcitoninemic patients without MTC. CONCLUSIONS: Basal
      CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is
      not a specific marker of MTC, its routine measurement represents a useful tool in
      the pre-operative evaluation of NTD patients, particularly those >40 yr old
      presenting with nodules <10 mm, even when FNAC does not show malignant features.
      To our knowledge, this is the first trial using ILMA to assess the ability of pre
      operative CT measurement to predict MTC in a large series of NTD patients.

PMID- 16794367
TI  - Incidence and prevalence rate estimation of GH treatment exposure in Piedmont
      pediatric population in the years 2002-2004: Data from the GH Registry.
AB  - OBJECTIVE: The aim of this study is to estimate the annual incidence and
      prevalence rate of the GH treatment exposure in patients under the age of 18
      treated for hypopituitarism or isolated GH deficiency (GHD) in Piedmont, during
      the period January 1, 2002 to December 31, 2004. METHODS: The selection criteria
      for recombinant human GH (rhGH) treatment in childhood were approved by the
      Ministry of Health in Italy in the yr 1998. The present analysis is based on data
      from the Registry of subjects receiving GH therapy (GH Registry) made up of the
      918 pediatric patients (age <18 yr) with a diagnosis of GHD (excluding Prader
      Willi and Turner syndromes and other conditions), diagnosed in the period January
      1, 2002 - December 31, 2004. The case series has been described as regards the
      number of cases per year of diagnosis; the prevalence and incidence rates,
      calculated per 10,000 (per ten thousand) inhabitants, are given for each year of
      the study period. RESULTS: The prevalence rate increases slightly from 8.62 per
      thousand in 2002 to 9.44 per thousand in 2004 and the incidence rates estimated
      were 2.49 per ten thousand, 1.86 per ten thousand and 1.97 per ten thousand in
      the yr 2002, 2003 and 2004, respectively. CONCLUSION: The Piedmont GH Registry
      represents the first database available in Italy and could set an example for the
      other Italian regions as well.

PMID- 16794368
TI  - Persistent and moderate hypercalcemia related to an ovarian clear cell
      adenocarcinoma: Pre- and postoperative parathyroid hormone related-peptide and
      1,25-dihydroxyvitamin D3 levels.
AB  - OBJECTIVE: To evaluate the role of PTH-related peptide (PTH-rP) and 1,25
      dihyhydroxyvitamin D3 in a case of hypercalcemia related to an ovarian
      adenocarcinoma. DESIGN: We report a case of humoral hypercalcemia in a patient
      aged 74 yr with a clear cell adenocarcinoma of the right ovary at an early stage
      of its development (stage T1aN0M0) revealed by moderate and persistent
      hypercalcemia (variable level between 2.7 and 3.2 mmol/l without any treatment)
      over six months. METHODS: PTH-rP and 1,25-dihydroxyvitamin D3 were measured in
      blood samples taken before and after hysterectomy and bilateral
      salpingooophorectomy and in blood samples taken intraoperatively from the right
      ovarian vein and a peripheral vein. RESULTS: High levels of plasma PTH-rP and
      1,25-dihydroxyvitamin D3 concomitant with high serum calcium and low PTH levels
      were found before surgery, which was followed by normalisation of all parameters
      studied. A concentration gradient was found regarding plasma PTHrP (right ovarian
      vein 60.4 pmol/l, peripheral vein 4.5 pmol/l), not 1,25-dihydroxyvitamin D3.
      CONCLUSION: 1) moderate and persistent hypercalcemia can be observed at an early
      stage of an ovarian carcinoma; 2) the gradient of PTH-rP concentration between
      the samples taken from the right ovarian vein and a peripheral vein provides
      evidence for a direct secretion of PTH-rP by the ovarian tumor; 3) the increased
      1,25-dihydroxyvitamin D3 level is not related to a direct ovarian production, but
      is a consequence of PTH-rP secretion.

PMID- 16794369
TI  - MEN1 family with a novel frameshift mutation.
AB  - Multiple endocrine neoplasm type 1 (MEN1) syndrome predisposes to the development
      of endocrine and non-endocrine tumors with an autosomal dominant pattern of
      inheritance. Different mutations have been found throughout the gene with a
      variable phenotype expression. The proband, a Caucasian man, was admitted to our
      department in 2001, at the age of 51 because of a 1-yr history of diarrhoea and
      hypertension. He reported a previous intestinal resection for bowel occlusion
      with a histological diagnosis of unspecified mesenchymal neoplasia. He had also
      undergone a left adrenalectomy for a large nonfunctioning adrenal adenoma.
      Subsequently, he had suffered from gastralgia and melena; a gastroduodenoscopy
      showed an erosive gastritis. His family history was negative for endocrine
      disorders. On physical examination, multiple abdominal cutaneous lipomas and
      facial angiofibromas were observed. Biochemical screening revealed a primary
      hyperparathyroidism and an increase in circulating levels of PRL, chromogranin-A,
      gastrin and glucagon. The whole body computed tomography (CT) scan, the 111In
      octreotide scan and the pituitary magnetic resonance imaging (MRI) did not reveal
      any abnormality. The presence of small neuroendocrine tumors was suspected by a
      positron emission tomography uptake in the epigastric region. The endoscopic
      ultrasound revealed a pancreatic lesion sized 1.1 cm that is under evaluation.
      Direct DNA sequencing analysis of the proband MEN1 gene revealed the 579delG
      frameshift mutation in the exon 3. The genetic screening of the family revealed
      the same mutation in 3 out of 5 offspring. The biochemical screening revealed
      some features of the MEN1 syndrome in all three of them. In conclusion, a novel
      frameshift MEN1 mutation was found in kindred with an apparently negative family
      history. Our experience confirms that MEN1 syndrome is a complex and
      underestimated condition, unless specifically investigated by trained
      specialists.

PMID- 16794370
TI  - An uncommon large deletion in the androgen-receptor gene in a XY female with
      complete androgen insensitivity syndrome.
AB  - Androgen insensitivity is a disorder characterized by an abnormal male sexual
      development, in which the androgen action is impaired due to structural defects
      in the androgen receptor gene. We report a case of a 46,XY subject with female
      phenotype (normal breast and external genitalia) lacking sexual hair, affected
      with primary amenorrhea. In this patient, we found a deletion of a large region
      of the androgen receptor gene encoding the steroid-binding domain of the protein,
      causing a complete inability to bind the androgens. This uncommon molecular
      defect impaired the expression of androgen-dependent genes inducing the female
      phenotype.

PMID- 16794371
TI  - Pituitary size fluctuation in long-term MR studies of PROP1 deficient patients: A
      persistent pathophysiological mechanism?
AB  - Inactivating PROP1 gene alterations are responsible for over 50% of familial
      combined pituitary hormone deficiency cases. Pituitary enlargement followed by
      regression and subnormal pituitary size has been documented in a number of PROP1
      deficient patients. Data derived from PROP1 deficient mice (Ames dwarfs) have
      revealed some of the underlying cellular mechanisms. Nevertheless, long-term
      magnetic resonance imaging (MRI) findings in two PROP1 deficient patients suggest
      the evolution of pituitary pathology as more complex and persistent than
      previously described. Patient A had enlarged pituitary gland (pituitary height: 9
      10 mm), demonstrated by serial MRI carried out from age 5 to 8.5 yr, small
      pituitary gland (4 mm) at age 10 yr and pituitary enlargement (11 mm) at age 19
      yr. Patient B had a pituitary gland of normal size at age 7 yr (5 mm), whereas at
      age 14.3 and 16.3 yr, an enlarged pituitary gland was disclosed (10 and 11 mm,
      respectively). Both series of events are suggestive of a persistent
      pathophysiological mechanism in the pituitary gland of patients with PROP1 gene
      defects. Therefore, long-term pituitary follow-up by MRI in such patients may be
      necessary even in the case of a small or normal pituitary gland. It must be noted
      that current data from the Ames dwarf mouse cannot fully explain the observed
      pituitary size fluctuation.

PMID- 16794372
TI  - Preventing skeletal complications in androgen deprived men with prostate cancer:
      Time for action.

PMID- 16794374
TI  - [Effect of anti-retroviral therapy on body composition changes: a literature
      review].
AB  - Protein-energetic malnutrition, characterized by both lean mass and fat
      depletion, was common in the pre-HAART era, and was associated with shortened
      survival and diminished quality of life. The pathogenesis of protein-energy
      malnutrition was multifactorial, and nutritional treatments were largely
      ineffective in the absence of disease stabilization. The introduction of HAART
      brought markedly improved outcomes, including a decrease in the incidence of
      malnutrition. However, other nutritional and metabolic alterations were noticed,
      and included changes in body shape, both lipoatrophy and lipohypertrophy, as well
      as changes in metabolism, notably hyperlipidemia and insulin resistance. These
      conditions, though sometimes occurring together, may occur independently,
      suggesting a complex, multifactorial cause. Several mechanisms have been
      hypothesized, including impairment to adipocyte differentiation and adipokine
      regulation, production of proinflammatory cytokines and mitochondrial toxicity.
      The role of the single drug class is still unclear, because both PI and NRTI have
      been associated with the syndrome, and the therapeutic protocols include both
      groups. Most of the medical therapies proposed for lipodystrophy are ineffective,
      and even if surgery remains an alternative, it is not associated with long
      lasting outcomes.

PMID- 16794373
TI  - Endogenous subclinical hypercortisolism: Diagnostic uncertainties and clinical
      implications.
AB  - Subclinical hypercortisolism (SH) is a newly characterized hormonal disorder that
      is almost exclusively detected in the context of incidentally discovered adrenal
      masses. The diagnostic criteria used for the definition of this condition are at
      present controversial. Amongst the various tests used for the detection of this
      abnormality (dexamethasone suppression, urinary free cortisol, ACTH levels,
      midnight serum or salivary cortisol concentrations, ACTH responses to CRH
      stimulation), the dexamethasone suppression tests (DST) seem to better accomplish
      the task of unmasking subtle abnormalities of cortisol secretion. Several
      versions of DST have been used: the 1-mg overnight, the 3-mg overnight and the
      classical 2-day low-dose DST. This latter test has the theoretical advantage
      that, by more efficiently suppressing pituitary ACTH secretion, it may provide a
      measure of the residual (ie non- ACTH-dependent) cortisol secretion from the
      adrenal mass. In this way, post-dexamethasone cortisol concentrations may
      quantify the degree of autonomous cortisol hypersecretion. In fact, post
      dexamethasone cortisol concentrations have a negative correlation with basal ACTH
      levels and a positive correlation with midnight cortisol concentrations as well
      as the size of the incidentally discovered adrenal mass. Most of the existing
      data indicate that SH detected in the context of adrenal incidentalomas may have
      some clinically significant implications. In fact, patients with higher post
      dexamethasone cortisol concentrations demonstrate higher lipid levels and lower
      bone mass densities. It has also been suggested that SH may be responsible for
      biochemical and phenotypic changes reminiscent of the metabolic syndrome. In
      summary, SH does exist and is associated with a negative impact in patients'
      health; however, hormonal cut-off criteria for decision-making remain to be
      defined.

PMID- 16794375
TI  - [Health care and infective aspects in patients affected by common variable
      immunodeficiency assisted in the Lazio Regional Authority Reference Centre for
      Primary Immunodeficiencies].
AB  - Common variable immunodeficiency (CVID) is a chronic condition characterised by a
      predominant defect of humoral immunity. In most cases the diagnosis of CVID is
      made during adulthood; the main clinical features of CVID are chronic and
      relapsing infections (mainly of respiratory and gastroenteric tracts). CVID
      patients may also develop neoplastic and autoimmune diseases. In our centre (the
      Regional Centre for Primary Immunodeficiencies of the Lazio Regional Authority)
      we administered a 23-item questionnaire to 60 patients with CVID undergoing
      substitutive therapy with intravenous immunoglobulins (IVIG) about their
      demographic characteristics, time of clinical onset, time of diagnosis of CVID,
      clinical features, IVIG doses and administration intervals, and self-assessment
      of health status. In addition, the clinical history of all patients was reviewed,
      and the levels of serum IgG, IgA and IgM were evaluated and compared with the pre
      therapy serum concentration. Moreover, an analysis of the treatment costs was
      performed. At onset, 67.2% of patients presented recurrent respiratory
      infections, and 50% had infections of the lower respiratory tract; 39.6% of the
      patients had gastroenteric infections. Most patients (57%) had recurrent
      infections of at least 2 of the respiratory, gastroenteric and/or urogenital
      tracts. In 37.9% of the group the diagnosis of CVID was made in less than 2 years
      after the beginning of symptoms, but in many cases (22.4%) the diagnosis took
      more than 10 years. 93% of patients are treated with a dose of IVIG between 6 and
      15 g per administration, with intervals between 2 and 3 weeks. The review of
      patients'clinical history showed that 43% of patients have had respiratory
      infections during the follow-up in our Centre, 43% have splenomegaly (3% were
      also subjected to splenectomy) and 18.3% have autoimmune diseases. The mean
      concentration of IgG before the beginning of IVIG therapy was 235 mg/dl, while
      during the follow-up it was 664 mg/dl. Given the long time often required for
      diagnosis, general physicians and specialists should be better informed in order
      to make diagnosis swifter. The substitutive therapy with IVIG is effective in
      preventing recurrent infections and complications. A thorough follow-up is
      important for diagnosing neoplastic and autoimmune complications; in addition,
      immunologic analysis of peripheral blood and bone marrow are useful in
      identifying subgroups of patients with more severe clinical features. Finally, in
      selected patients, treatment costs may be controlled by modifying the dosage of
      IVIG or the intervals between administrations.

PMID- 16794376
TI  - [Cardiac manifestations during viral acute hepatitis].
AB  - The authors describe a retrospective study conducted on 46 patients with acute
      viral hepatitis, searching for cardiac disorders. These disorders appeared in
      about 43% of cases, only with benign evolution. The most frequent alterations are
      electrocardiographic disorders, followed by conduction blocks, axis deviations
      and arrhythmias. Acute pericarditis was also described, associated with HCV
      infection. The viral agents most frequently involved are HBV and HCV, followed by
      cytomegalovirus, and Epstein-Barr virus. In conclusion, the incidence of cardiac
      manifestations during viral acute hepatitis is rather high, but with benign
      evolution.

PMID- 16794377
TI  - [Hyperlactacidemia during antiretroviral therapy: frequency and clinical
      therapeutic correlations].
AB  - While asymptomatic hyperlactacidemia is quite a frequent phenomenon among HIV
      infected patients treated with highly active antiretroviral therapy (HAART),
      lactic acidosis is a rare, but potentially life-threatening occurrence.
      Epidemiology, clinical and laboratory presentation, evolution, and outcome of
      this phenomenon are currently under intensive investigation, and the most likely
      pathogenetic pathways seem to involve mitochondrial toxicity prompted by the
      administration of nucleoside reverse transcriptase inhibitors. Our case-control
      study on an extensive, single centre population treated for HIV infection
      provides novel insights on these emerging issues, reported and discussed on the
      basis of the most recently published findings.

PMID- 16794378
TI  - Fatal haemolytic uraemic syndrome in an AIDS patient with disseminated adenovirus
      and cytomegalovirus co-infection.
AB  - We describe a fatal case of haemolytic uraemic syndrome in a young woman with
      AIDS, and disseminated adenovirus (ADV) and cytomegalovirus (CMV) co-infection.
      We hypothesize that ADV/CMV co-infection may have a causative role in this
      clinical picture.

PMID- 16794379
TI  - Clinical efficacy of intravenous colistin therapy in combination with ceftazidime
      in severe MDR P. aeruginosa systemic infections in two haematological patients.
AB  - Nosocomial infections due to MDR P. aeruginosa are an increasing problem.
      Therapeutical options are few. We describe two haematological patients with
      severe neutropenia and systemic infection due to MDR P. aeruginosa treated
      successfully with colistin plus ceftazidime. Severe adverse events were not
      described.

PMID- 16794380
TI  - [Syphilis in sixteenth-century in Bologna. Health care and social assistance
      (Part one)].
AB  - Syphilis arrived in Bologna in the summer of 1495, after Fornovo's battle on the
      Taro where Charles VIII's army, following the invasion of Naples, fought against
      the anti-French league who faced up to the invaders as they withdrew. It was the
      battle-weary Bolognesi, prisoners, deserters and probably some prostitutes
      following the French and mercenary army who introduced the infection into the
      city. At the beginning of the syphilis epidemic, the disease was very aggressive
      with particularly visible symptoms and many resulting deaths. Subsequently,
      contemporaries mention an abatement of this aggressivity in time spans that
      varied, but in no cases exceeded 60 years. In 1507 Bologna lost its political
      autonomy, becoming dependent on Rome. This was symptomatic of the upheavals
      throughout Italy in the sixteenth century. In this situation of economic and
      institutional crisis the Bolognesi were able to react with decision to the
      epidemic, re-converting the municipal hospital dedicated to S. Maria dei Guarini
      during the sixteenth century. This hospital, specializing in treating syphilis,
      was called "Ospedale di San Giobbe". It was closed in 1798, after the entry of
      the French army into Bologna. In 1560 the Bolognesi, realising that the most
      important causes of the spread of syphilis were social degradation, prostitution
      and poverty, founded another institution for the poor and for the prevention of
      prostitution. This institution was developed by the Opera dei Mendicanti and
      provided hospitality during the 1590 famine, in a city of 55,000 inhabitants, for
      as many as 1400 poor and sick. We also present the cure (guaiac and mercury) that
      they used at the time against syphilis. In such a difficult historical period
      beset with political and economic problems, the Bolognesi established two
      important institutions and showed that social solidarity is a value for the whole
      population.

PMID- 16794381
TI  - Early removal of prophylactic drains reduces the risk of intra-abdominal
      infections in patients with pancreatic head resection: prospective study for 104
      consecutive patients.
AB  - OBJECTIVE: The aim of this study was designed to determine whether the period of
      drain insertion influences the incidence of postoperative complications.
      BACKGROUND DATA: The significance of prophylactic drains after pancreatic head
      resection is still controversial. No report discusses the association of the
      period of drain insertion and postoperative complications. METHODS: A total of
      104 consecutive patients who underwent pancreatic head resection were enrolled in
      this study. To assess the value of prophylactic drains, we prospectively assigned
      the patients into 2 groups: group I underwent resection from January 2000 to
      January 2002 (n = 52, drain to be removed on postoperative day 8); group II
      underwent resection from February 2002 to December 2004 (n = 52, drain to be
      removed on postoperative day 4). Postoperative complications in the 2 groups were
      compared. RESULTS: The rate of pancreatic fistula was significantly lower in
      group II (3.6%) than in group I (23%) (P = 0.0038). The rate of intra-abdominal
      infections, including intra-abdominal abscess and infected intra-abdominal
      collections, was significantly reduced in group II (7.7%) compared with group I
      (38%) (P = 0.0003). Eighteen of 52 (34.6%) patients in group I had an inserted
      drain beyond 8 days, whereas only 2 of 52 (3.7%) patients in group II had an
      inserted drain beyond 4 days (P = 0.0002). Cultures of drainage fluid were
      positive in 16 of 52 (30.8%) patients in group I, and in 2 of 52 (3.7%) patients
      in group II (P = 0.0002). Intraoperative bleeding (> 1500 mL), operative time (>
      420 minutes, and the period of drain insertion were significant risk factors for
      intra-abdominal infections (P = 0.043, 0.025, 0.0003, respectively). The period
      of drain insertion was the only independent risk factor for intra-abdominal
      infections by multivariate analysis (odds ratio, 6.7). CONCLUSION: Drain removal
      on postoperative day 4 was shown to be an independent factor in reducing the
      incidence of complications with pancreatic head resection, including intra
      abdominal infections.

PMID- 16794382
TI  - Evidence forward, drainage on retreat: still we ignore and drain!?

PMID- 16794383
TI  - One thousand consecutive pancreaticoduodenectomies.
AB  - OBJECTIVE: To trace the evolution of pancreaticoduodenectomy from the decade of
      the 1960s through the first decade of the new Millenium, through the experience
      of one surgeon doing 1000 consecutive operations. SUMMARY BACKGROUND DATA: A
      regional resection of the head of the pancreas was first performed successfully
      by Kausch in 1909. The operation was popularized by Whipple in 1935, who reported
      3 pancreaticoduodenectomies. Because of a hospital mortality of approximately
      25%, the operation was performed infrequently until the 1980s. From the 1980s on,
      experience with this complex alimentary tract operation increased, and high
      volume centers developed. This resulted in a significant drop in hospital
      mortality and allowed institutions and individuals to gain large experiences.
      METHODS: Between March 1969 and May 2003, 1000 consecutive
      pancreaticoduodenectomies were performed by a single surgeon. A retrospective
      review of a prospectively maintained database was performed to determine the
      management and outcome of these patients, as well as to document the evolution of
      this operative procedure over 5 decades. RESULTS: The median operative time
      decreased significantly over the decades, being 8.8 hours in the 1970s and 5.5
      hours during the 2000s. Postoperative length of stay dropped from a median of 17
      days in the 1980s to 9 days in the 2000s. There were only 10
      postoperative/hospital deaths, for a mortality of 1%. A total of 405 patients
      underwent pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas.
      Overall 5-year survival was 18%; for the lymph node-negative patients, it was
      32%; and for node-negative, margin-negative patients, it was 41%. CONCLUSIONS:
      Pancreaticoduodenectomy has become a commonly performed operation in many
      tertiary care centers. Operative time, blood loss, and length of stay have
      dropped substantially. The operation has become safe, with a low hospital
      mortality. It has become an effective operation for pancreatic cancer in those
      patients in whom their tumor is margin negative and node negative.

PMID- 16794384
TI  - Pancreaticoduodenectomy: the golden era.

PMID- 16794385
TI  - A comparison of hand-sewn versus stapled ileal pouch anal anastomosis (IPAA)
      following proctocolectomy: a meta-analysis of 4183 patients.
AB  - OBJECTIVE: Using meta-analytical techniques, the study compared postoperative
      adverse events and functional outcomes of stapled versus hand-sewn ileal pouch
      anal anastomosis (IPAA) following restorative proctocolectomy. BACKGROUND: The
      choice of mucosectomy and hand-sewn versus stapled pouch-anal anastomosis has
      been a subject of debate with no clear consensus as to which method provides
      better functional results and long-term outcomes. METHODS: Comparative studies
      published between 1988 and 2003, of hand-sewn versus stapled IPAA were included.
      Endpoints were classified into postoperative complications and functional and
      physiologic outcomes measured at least 3 months following closure of ileostomy or
      surgery if no proximal diversion was used, quality of life following surgery, and
      neoplastic transformation within the anal transition zone. RESULTS: Twenty-one
      studies, consisting of 4183 patients (2699 hand-sewn and 1484 stapled IPAA) were
      included. There was no significant difference in the incidence of postoperative
      complications between the 2 groups. The incidence of nocturnal seepage and pad
      usage favored the stapled IPAA (odds ratio [OR] = 2.78, P < 0.001 and OR = 4.12,
      P = 0.007, respectively). The frequency of defecation was not significantly
      different between the 2 groups (P = 0.562), nor was the use of antidiarrheal
      medication (OR = 1.27, P = 0.422). Anorectal physiologic measurements
      demonstrated a significant reduction in the resting and squeeze pressure in the
      hand-sewn IPAA group by 13.4 and 14.4 mm Hg, respectively (P < 0.018). The
      stapled IPAA group showed a higher incidence of dysplasia in the anal transition
      zone that did not reach statistical significance (OR = 0.42, P = 0.080).
      CONCLUSIONS: Both techniques had similar early postoperative outcomes; however,
      stapled IPAA offered improved nocturnal continence, which was reflected in higher
      anorectal physiologic measurements. A risk of increased incidence of dysplasia in
      the ATZ may exist in the stapled group that cannot be quantified by this study.
      We describe a decision algorithm for the choice of IPAA, based on the relative
      risk of long-term neoplastic transformation.

PMID- 16794386
TI  - Prophylactic ilioinguinal neurectomy in open inguinal hernia repair: a double
      blind randomized controlled trial.
AB  - OBJECTIVE: We conducted a double-blinded randomized controlled trial to
      investigate the short- to mid-term neurosensory effect of prophylactic
      ilioinguinal neurectomy during Lichtenstein repair of inguinal hernia. METHOD:
      One hundred male patients between the age of 18 and 80 years with unilateral
      inguinal hernia undergoing Lichtenstein hernia repair were randomized to receive
      either prophylactic ilioinguinal neurectomy (group A) or ilioinguinal nerve
      preservation (group B) during operation. All operations were performed by
      surgeons specialized in hernia repair under local anesthesia or general
      anesthesia. The primary outcome was the incidence of chronic groin pain at 6
      months. Secondary outcomes included incidence of groin numbness, postoperative
      sensory loss or change at the groin region, and quality of life measurement
      assessed by SF-36 questionnaire at 6 months. All follow-up and outcome measures
      were carried out by a designated occupational therapist at 1 and 6 months
      following surgery in a double-blinded manner. RESULTS: The incidence of chronic
      groin pain at 6 months was significantly lower in group A than group B (8% vs.
      28.6%; P = 0.008). No significant intergroup differences were found regarding the
      incidence of groin numbness, postoperative sensory loss or changes at the groin
      region, and quality of life measurement at 6 months after the operation.
      CONCLUSIONS: Prophylactic ilioinguinal neurectomy significantly decreases the
      incidence of chronic groin pain after Lichtenstein hernia repair without added
      morbidities. It should be considered as a routine surgical step during the
      operation.

PMID- 16794387
TI  - Five-year subjective and objective results of laparoscopic and conventional
      Nissen fundoplication: a randomized trial.
AB  - OBJECTIVE: The purpose of this prospective study was to compare the subjective
      and objective outcome of laparoscopic (LNF) and conventional Nissen
      fundoplication (CNF) up to 5 years after surgery as obtained in a multicenter
      randomized controlled trial. SUMMARY OF BACKGROUND DATA: LNF is regarded as
      surgical treatment of first choice for refractory gastroesophageal reflux disease
      by many surgeons based on several short- and mid-term studies. The long-term
      efficacy of Nissen fundoplication, however, is still questioned as objective data
      gathered from prospective studies are lacking. METHODS: From 1997 to 1999, 177
      patients were randomized to undergo LNF or CNF. Five years after surgery, all
      patients were requested to fill in questionnaires and to undergo esophageal
      manometry and 24-hour pH-metry. RESULTS: A total of 148 patients agreed to
      participate in the follow-up study: 79 patients after LNF and 69 after CNF. Of
      these, 97 patients (48 LNF, 49 CNF) consented to undergo esophageal manometry and
      24-hour pH-metry. At 5 years follow-up, 20 patients had undergone reoperation: 12
      after LNF (15%) and 8 after CNF (12%). There was no difference in subjective
      outcome, with overall satisfaction rates of 88% and 90%, respectively. Total
      esophageal acid exposure times (pH < 4) were 2.1% +/- 0.5% and 2.0% +/- 0.6%,
      respectively (P = 0.21). Antisecretory medication was taken daily in 14% and 16%,
      respectively (P = 0.29). There was no correlation between medication use and acid
      exposure and indices of symptom-reflux association (symptom index and symptom
      association probability). No significant differences between subjective and
      objective results at 3 to 6 months and results obtained at 5 years after surgery
      were found. CONCLUSIONS: The effects of LNF and CNF on general state of health
      and objective reflux control are sustained up to 5 years after surgery and the
      long-term results of LNF and CNF are comparable. A substantial minority of
      patients in both groups had a second antireflux operation or took antisecretory
      drugs, although the use of those medications did not appear to be related to
      abnormal esophageal acid exposure.

PMID- 16794388
TI  - Repair of 104 failed anti-reflux operations.
AB  - OBJECTIVE: To assess whether reoperative surgery for failed Nissen fundoplication
      is beneficial and to classify all mechanisms of failure recognized. SUMMARY
      BACKGROUND DATA: Antireflux surgery is often necessary, but a 10% failure rate is
      commonplace. We report results for patients undergoing reoperative surgery and
      present a nomenclature of mechanisms of failure. METHODS: A total of 104
      patients, who had a previous fundoplication for gastroesophageal reflux disease
      (GERD), underwent reoperative surgery. Manometry (n = 86), endoscopy (n = 101),
      pH monitoring (n = 27), upright esophagram (n = 90), gastric emptying (n = 26),
      and symptom assessment (n = 104) were performed prior to reoperative surgery.
      Patients were also assessed before and during reoperation for mechanism of
      failure using a newly proposed classification. The operative approach was
      laparoscopic in 58 patients, via open laparotomy in 12, and a thoracotomy in 34
      patients. Follow-up was conducted by phone interview and was completed in 97
      patients (97%; 3 were deceased) with a mean follow-up of 32 months (range, 1-146
      months). RESULTS: The conversion rate to laparotomy for laparoscopic patients was
      8%. The perioperative complication rate was 32%. One patient died of respiratory
      insufficiency after a laparotomy. Seven patients required additional surgery for
      correction of persistent or recurrent symptoms. The short and long-term
      complication rate was similar for the different operative approachs. Symptom
      resolution (rare or absent) occurred in 74% of patients with dysphagia, 75% with
      heartburn, 85% with regurgitation, and 94% with chest pain. The overall post
      reoperative patient satisfaction was 7 on a scale of 1 to 10 and 3 on a scale of
      1 to 4 when patients were asked to grade the operative result. There was no
      difference in the symptom resolution for patients operated upon by the
      laparoscopic approach as compared with laparotomy, but those patients undergoing
      a Collis gastroplasty had poorer results. The preoperative accuracy of assessment
      for mechanism of failure was 78%. A nomenclature of mechanisms of failure is
      included to aide reoperative assessment and new mechanisms of failure are
      described. CONCLUSION: Reoperative surgery results for GERD are satisfactory. A
      variety of operative approaches proved equally effective. Poorer results were
      observed in patients with more advanced disease.

PMID- 16794389
TI  - Genetic differentiation of appendiceal tumor malignancy: a guide for the
      perplexed.
AB  - OBJECTIVE: To use differential gene expression of candidate markers to
      discriminate benign appendiceal carcinoids (APCs) from malignant and mixed cell
      APCs. SUMMARY BACKGROUND DATA: Controversy exists in regard to the appropriate
      surgical management of APCs since it is sometimes difficult to predict tumor
      behavior using traditional pathologic criteria. We have identified 5
      differentially expressed genes (a mitosis-regulatory gene NAP1L1, an adhesin MAGE
      D2, an estrogen-antagonist, the metastasis marker MTA1, the apoptotic marker
      NALP, and chromogranin A) that define gut neuroendocrine cell behavior. METHODS:
      Total RNA was isolated using TRIzol reagent from 42 appendiceal samples,
      including appendiceal carcinoids identified at exploration for appendicitis (no
      evidence of metastasis; n = 16), appendicitis specimens (n = 11), malignant
      appendiceal tumors (> 1.5 cm, evidence of metastatic invasion; n = 7), and mixed
      (goblet) cell appendiceal adenocarcinoids (n = 3), normal appendiceal tissue (n =
      5), and 5 colorectal cancers. Gene expression (CgA, NAP1L1, MAGE-D2, MTA1, and
      NALP1) was examined by Q-RT PCR (Applied Biosystems) and quantified against
      GAPDH. RESULTS: CgA message was elevated (> 1000-fold, P < 0.05) in all tumor
      types. NAP1L1 was elevated (> 10-fold, P < 0.03) in both malignant and goblet
      cell adenocarcinoids compared with normal and incidental lesions (P < 0.006).
      MAGE-D2 and MTA1 message were significantly elevated (> 10-fold, P < 0.01) in the
      malignant and goblet cell adenocarcinoid tumors but not in the appendicitis
      associated carcinoids or normal mucosa. The apoptotic marker, NALP1, was
      overexpressed (> 50-fold, P < 0.05) in the appendicitis-associated and malignant
      appendiceal carcinoids but was significantly decreased (> 10-fold, P < 0.05) in
      the goblet cell adenocarcinoids. Elevated CgA transcript and protein levels
      indicative of a carcinoid tumor were identified in one acute appendicitis sample
      with no histologic evidence of a tumor. CONCLUSIONS: These data demonstrate that
      malignant APCs and goblet cell adenocarcinoids have elevated expression of
      NAP1L1, MAGE-D2, and MTA1 compared with appendiceal carcinoids identified at
      surgery for appendicitis. This and the differences in NALP1 gene expression
      (decreased in goblet cell adenocarcinoids) provide a series of molecular
      signatures that differentiate carcinoids of the appendix. CgA identified all
      appendiceal tumors as well as covert lesions, which may be more prevalent than
      previously recognized. The molecular delineation of malignant appendiceal tumor
      potential provides a scientific basis to define the appropriate surgical
      management as opposed to morphologic assessment alone.

PMID- 16794390
TI  - Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and
      pancreatic endocrine neoplasias.
AB  - OBJECTIVE: The aim of this study was to evaluate the results of pancreatic
      resection in pancreatic endocrine neoplasias (PENs) in patients affected by
      multiple endocrine neoplasia type 1 (MEN1) syndrome. BACKGROUND: Since these
      tumors often show an indolent course, the role of diagnostic procedures and type
      of surgical approach are controversial. Experience with new diagnostic approaches
      and more aggressive surgery is still limited. METHODS: Sixteen MEN1 patients were
      referred to our Surgical Unit (1992-2003) and were operated on for the
      indications of hypergastrinism, hypoglycemia, and/or pancreatic endocrine
      neoplasias larger than 1 cm. Zollinger-Ellison syndrome (ZES) was present in 13
      patients, 2 of whom experienced a recurrence after previous surgery. Preoperative
      tumor localization was carried out using ultrasonography (US), computed
      tomography (CT), endoscopic ultrasonography (EUS), somatostatin receptor
      scintigraphy (SSRS), or selective arterial secretin injection (SASI). Rapid
      intraoperative gastrin measurement (IGM) was carried out in 8 patients, and 1
      patient also underwent an intraoperative secretin provocative test. RESULTS:
      Either pancreatoduodenectomy (PD) or total pancreatectomy (TP) or distal
      pancreatectomy was performed. There was no postoperative mortality; 37%
      complications included pancreatic (27%) and biliary (6%) fistulas, abdominal
      collection (6%), and acute pancreatitis (6%). EUS and SSRS were the most
      sensitive preoperative imaging techniques. At follow-up, 10 of 13
      hypergastrinemic patients (77%) are currently eugastrinemic with negative
      secretin provocative test, while 3 are showing a recurrence of the disease. All
      patients affected by insulinoma were cured. CONCLUSIONS: MEN1 tumors should be
      considered surgically curable diseases. IGM may be of value in the assessment of
      surgical cure. Our experience suggests that PD is superior to less radical
      surgical approaches in providing cure with limited morbidity in MEN1 gastrinomas
      and pancreatic neoplasias.

PMID- 16794391
TI  - Right portal vein embolization before right hepatectomy for unilobar colorectal
      liver metastases reduces the intrahepatic recurrence rate.
AB  - AIM: To assess the effect of portal vein embolization (PVE) on intrahepatic
      recurrence rate after right hepatectomy for unilobar colorectal liver metastases
      (CLM). SUMMARY AND BACKGROUND: Recent research suggests that CLM could spread
      retrogradely through the portal vein. PVE may reduce tumor shedding by the
      occlusion of distal portal branches. However, no study reported the clinical
      effect of PVE on intrahepatic recurrence after CLM resection. PATIENTS AND
      METHODS: Between 1995 and 2003, 44 patients requiring a right hepatectomy for
      unilobar CLM were operated in our institution. Right hepatectomy was performed
      after PVE in 23 patients (group A) and without PVE in 21 (group B). Surgical
      outcome and site of recurrence were analyzed. RESULTS: The postoperative
      mortality was nil. Overall morbidity and transitory liver failure rates were
      similar in groups A and B (43.4% and 17.3% vs. 33.3% and 14.2%, respectively).
      The 3- and 5-year overall survival rates did not differ in group A and B patients
      (61.2% and 43.7% vs. 49.7% and 35.5%, respectively; P = 0.862). The disease-free
      survival rate was similar in both groups. Thirty patients (68.2%) developed
      recurrences. Recurrences were intrahepatic in 22 patients (50%) and extrahepatic
      in 27 (61.3%). Intrahepatic recurrence rate was significantly lower in group A
      compared with group B (26.0% vs. 76.1% respectively; P < 0.001). PVE, number of
      CLM, and administration of neoadjuvant chemotherapy were independent prognostic
      factors for intrahepatic recurrences. CONCLUSION: This study showed that PVE
      reduces intrahepatic recurrence rate after right hepatectomy for unilobar CLM.

PMID- 16794392
TI  - Combined liver resection and reconstruction of the supra-renal vena cava: the
      Paul Brousse experience.
AB  - BACKGROUND: Liver tumors with inferior vena cava (IVC) involvement may require
      combined resection of the liver and IVC. This approach, with its high surgical
      risks and poor long-term prognosis, was precluded until the development of
      neoadjuvant chemotherapy, portal vein embolization, reinforced vascular
      prostheses, and technical advances in liver transplantation. METHODS: We reviewed
      22 cases of hepatectomy with retrohepatic IVC resection and reconstruction. The
      patients had a median age of 51.5 years (range, 32.8-75.3 years). Indications for
      resection were: liver metastases (n = 9), cholangiocarcinoma (n = 8),
      hepatocellular carcinoma (n = 2), other cancers (n = 3). The liver resections
      carried out included 18 first, 3 second, and one third hepatectomy. Segment 1
      (caudate lobe) was included in the specimen in 19 cases (86%). Resection
      concerned 1 to 6 liver segments (median = 5.0). Vascular control was achieved by
      vascular exclusion of the liver preserving the caval flow (n = 1), standard
      vascular exclusion of the liver (n = 12), in situ cold perfusion of the liver (n
      = 9). Ex situ surgery was not necessary in any case. Venovenous bypass was used
      in 12 cases. The IVC was reconstructed with a ringed Gore-Tex tube graft (n =
      10), primarily (n = 8), or by caval plasty (n = 4). A main hepatic vein was
      reimplanted in 6 cases: into the native IVC (n = 4) or into a Gore-Tex tube graft
      (n = 2). RESULTS: One patient died (4.5%) due to catheter infection, 7 days after
      in situ cold perfusion with replacement of the vena cava. Eight patients (36%)
      had no complications and 14 patients (64%) had 23 complications. In all but 1
      case, the complications were transient and successfully controlled. The patients
      stayed in intensive care for 3.3 +/- 2.0 days and in the hospital for 17.7 +/-
      7.8 days. All vascular reconstructions were patent at last follow-up. With median
      follow-up of 19 months, 10 patients died of tumor recurrence and eleven were
      alive with (n = 5) or without (n = 6) disease. Actuarial 1-, 3-, and 5-year
      survival rates were 81.8%, 38.3%, and 38.3%, respectively. CONCLUSIONS: IVC
      resection and reconstruction combined with liver resection can be safely
      performed in selected patients. The lack of alternative treatments and the
      spontaneous poor prognosis justify this approach, provided that surgery is
      carried out at a center specialized in both liver surgery and liver
      transplantation. The development of adjuvant chemotherapy regimens is required to
      improve the long-term results of this salvage surgery.

PMID- 16794393
TI  - Marginal hepatectomy in the rat: from anatomy to surgery.
AB  - OBJECTIVE: Based on the 3-dimensional visualization of vascular supply and
      drainage, a vessel-oriented resection technique was optimized. The new surgical
      technique was used to determine the maximal reduction in liver mass enabling a
      50% 1-week survival rate. BACKGROUND DATA: Determination of the minimal liver
      mass is necessary in clinical as well as in experimental liver surgery. In rats,
      survival seems to depend on the surgical technique applied. Extended hepatectomy
      with removal of 90% of the liver mass was long regarded as a lethal model.
      Introduction of a vessel-oriented approach enabled long-term survival in this
      model. METHODS: The lobar and vascular anatomy of rat livers was visualized by
      plastination of the whole organ, respectively, by corrosion casts of the portal
      vein, hepatic artery and liver veins. The three-dimensional models were used to
      extract the underlying anatomic structure. In 90% partial hepatectomy, the liver
      parenchyma was clamped close to the base of the respective liver lobes (left
      lateral, median and right, liver lobe). Piercing sutures were placed through the
      liver parenchyma, so that the stem of portal vein and the accompanying hepatic
      artery but also the hepatic vein were included. RESULTS: A 1-week survival rate
      of 100% was achieved after 90% hepatectomy. Extending the procedure to 95%
      resection by additional removal of the upper caudate lobe led to a 1-week
      survival rate of 66%; 97% partial hepatectomy, accomplished by additional
      resection of the lower caudate lobe only leaving the paracaval parts of the liver
      behind, resulted in 100% lethality within 4 days. CONCLUSIONS: Using a
      anatomically based, vessel-oriented, parenchyma-preserving surgical technique in
      95% liver resections led to long-term survival. This represents the maximal
      reduction of liver mass compatible with survival.

PMID- 16794394
TI  - Immunohistochemically demonstrated lymph node micrometastasis and prognosis in
      patients with gallbladder carcinoma.
AB  - OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node
      micrometastasis has a survival impact in patients with advanced gallbladder
      carcinoma (pT2-4 tumors). SUMMARY BACKGROUND DATA: The clinical significance of
      immunohistochemically detected lymph node micrometastasis recently has been
      evaluated in various tumors. However, few reports have addressed this issue with
      regard to gallbladder carcinoma. METHODS: A total of 1476 lymph nodes from 67
      patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent
      curative resection were immunostained with monoclonal antibody against
      cytokeratins 8 and 18. The results were correlated with clinical and pathologic
      features and with patient survival. RESULTS: Lymph node micrometastases were
      detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%)
      of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were
      single-cell events, and the remaining 16 were clusters. Five micrometastases were
      detected in the paraaortic nodes. Clinicopathologic features showed no
      significant associations with the presence of lymph node micrometastases.
      Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0
      disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was
      worse in the 23 patients with micrometastasis than in the 44 without
      micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight
      patients without any lymph node involvement had the best prognosis, whereas
      survival for the 11 patients with both types of metastasis was dismal. The grade
      of micrometastasis (single-cell or cluster) had no effect on survival. The Cox
      proportional hazard model identified perineural invasion, lymph node
      micrometastasis, and microscopic venous invasion as significant independent
      prognostic factors. CONCLUSIONS: Lymph node micrometastasis has a significant
      survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent
      macroscopically curative resection. Extensive lymph node sectioning with keratin
      immunostaining is recommended for accurate prognostic evaluation for patients
      with gallbladder carcinoma.

PMID- 16794395
TI  - High intra-abdominal pressure enhances the penetration and antitumor effect of
      intraperitoneal cisplatin on experimental peritoneal carcinomatosis.
AB  - OBJECTIVE: To investigate the role of increased intra-abdominal pressure (IAP) on
      the intratumoral accumulation and the antitumor effect of intraperitoneal
      cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the
      tolerance of IAP in pigs, as it is a large animal with a body size equivalent to
      humans. SUMMARY BACKGROUND DATA: To investigate if an active convection, driven
      by a positive IAP, increases cisplatin penetration and antitumor effectiveness in
      a model of advanced peritoneal carcinomatosis in rats. EXPERIMENTAL DESIGN: BDIX
      rats with macroscopic peritoneal tumors received cisplatin administered as
      intravenous injection (IV), conventional intraperitoneal injection (IP), or
      sustained intraperitoneal injection of cisplatin given in a large volume of
      solvent for maintaining IAP for 1 hour. Platinum tissue concentration was
      measured by atomic absorption spectroscopy (AAS), and platinum distribution into
      the tumor nodules was assessed by the particular-induced x-ray emission (PIXE)
      method. The antitumor effect was assessed in a survival experiment. The
      hemodynamic, local, and systemic tolerance of IAP, with or without cisplatin, was
      evaluated in Large White pigs. RESULTS: The maximum tolerated IAP was 22 mm Hg
      for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP
      injections, resulted in the increased concentration and depth of diffusion of
      platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment
      induced an extended survival of rats treated at an advanced stage of
      carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well
      tolerated when maintained stable for 2 hours. Renal failure occurred in pigs
      receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100
      mg was well tolerated. CONCLUSIONS: Intraperitoneal chemotherapy with increased
      IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor
      accumulation and the antitumor effect of cisplatin in rats bearing advanced
      peritoneal carcinomatosis. In preclinical conditions, the tolerance of sustained
      IAP was manageable in ventilated pigs.

PMID- 16794397
TI  - The influence of age and gender on resting energy expenditure in severely burned
      children.
AB  - INTRODUCTION: Recent evidence suggests that female severely burned children have
      higher endogenous anabolic hormone levels and a shorter ICU stay compared with
      males. The purpose of this study was to analyze the influence of age and gender
      on resting energy expenditure (REE) in severely burned children from acute
      hospitalization through 12 months postburn. METHODS: A total of 100 pediatric
      patients with > 40% total body surface area (TBSA) burn were enrolled in a
      prospective study and followed by indirect calorimetry measurements. The REE was
      expressed as actual REE kcal/d, percent of predicted REE, and REE/ body mass
      index (BMI). Statistical analysis was performed by Student t test and one-way
      ANOVA for repeated measures. Significance was accepted at P < 0.05. RESULTS: The
      measured REE was significantly higher in males versus females at all time points
      (P < 0.05). The percent of predicted REE was significantly higher in males versus
      females during the acute hospitalization, at discharge, 6 and 9 months postburn
      (P < 0.05). The REE/BMI showed a significant difference between males and females
      at the acute and discharge time period (P < 0.05). In children 3 to 9.9 years of
      age, the measured REE and the percent of predicted REE were significantly higher
      in males versus females during the acute study, at discharge and 6 months
      postburn (P < 0.05). The measured REE at discharge, 9 and 12 months postburn for
      children >10 years of age was significantly higher in males compared with females
      (P < 0.05). CONCLUSION: Data show that female children exert a decreased
      hypermetabolic response compared with male children, which may improve burn
      outcomes in females.

PMID- 16794396
TI  - Chemokine receptor CXCR4 expression in patients with melanoma and colorectal
      cancer liver metastases and the association with disease outcome.
AB  - OBJECTIVE: To determine the role of chemokine receptor (CR) expression in
      patients with melanoma and colorectal cancer (CRC) liver metastases. SUMMARY
      BACKGROUND DATA: Murine and in vitro models have identified CR as potential
      factors in organ-specific metastasis of multiple cancers. Chemokines via their
      respective receptors have been shown to promote cell migration to distant organs.
      METHODS: Patients who underwent hepatic surgery for melanoma or CRC liver
      metastases were assessed. Screening cDNA microarrays of melanoma/CRC cell lines
      and tumor specimens were analyzed to identify CR. Microarray data were validated
      by quantitative real-time RT-PCR (qRT) in paraffin-embedded liver metastases.
      Migration assays and immunohistochemistry were performed to verify CR function
      and confirm CR expression, respectively. RESULTS: Microarray analysis identified
      CXCR4 as the most common CR expressed by both cancers. qRT demonstrated CXCR4
      expression in 24 of 27 (89%) melanoma and 28 of 29 (97%) CRC liver metastases. In
      vitro treatment of melanoma or CRC cells with CXCL12, the ligand for CXCR4,
      significantly increased cell migration (P < 0.001). Low versus high CXCR4
      expression in CRC liver metastases correlated with a significant difference in
      overall survival (median 27 months vs. 10 months, respectively; P = 0.036). In
      melanoma, low versus high CXCR4 expression in liver metastases demonstrated no
      difference in overall survival (median 11 months vs. 8 months, respectively; P =
      not significant). CONCLUSIONS: CXCR4 is expressed and functional on melanoma and
      CRC cells. The ligand for CXCR4 is highly expressed in liver and may specifically
      attract melanoma and CRC CXCR4 (+) cells. Quantitative analysis of CXCR4 gene
      expression in patients with liver metastases has prognostic significance for
      disease outcome.

PMID- 16794398
TI  - A role of PPAR-gamma in androstenediol-mediated salutary effects on cardiac
      function following trauma-hemorrhage.
AB  - OBJECTIVE: To examine the mechanism by which androstenediol improves cardiac
      function following trauma-hemorrhage (T-H). SUMMARY BACKGROUND DATA:
      Androstenediol administration improves cardiovascular function and attenuates
      proinflammatory cytokine production following T-H. Activation of the peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) has been shown to be
      protective following ischemic conditions. We hypothesized that PPAR-gamma
      activation plays a role in the androstenediol-mediated salutary effects on
      cardiac function following T-H. METHODS: Male rats underwent laparotomy and
      hemorrhagic shock (40 mm Hg for 90 minutes), followed by resuscitation with 4
      times the shed blood volume in the form of Ringer's lactate. Androstenediol (1
      mg/kg body weight, i.v.) was administrated at the end of resuscitation. In a
      separate group of animals, a PPAR-gamma antagonist (GW9662) was administered
      simultaneously with androstenediol and animals were killed at 5 hours thereafter.
      RESULTS: A decrease in cardiac function and an increase in IL-6 and iNOS gene
      expression were observed following T-H. Androstenediol treatment normalized
      cardiac function, increased PPAR-gamma DNA binding activity, attenuated IL-6 and
      iNOS gene expressions, and reduced plasma IL-6. Plasma 15-deoxy-Delta12, 14
      prostaglandin J2 (PGJ2, an endogenous PPAR-gamma agonist) levels were also
      increased in androstenediol-treated T-H rats, but these levels were lower than
      those observed in shams. Coadministration of PPAR-gamma antagonist along with
      androstenediol, however, prevented the androstenediol-mediated reduction in
      cardiac iNOS and IL-6 expressions and abolished the improvements in cardiac
      function. CONCLUSION: The androstenediol-mediated salutary effects on cardiac
      function following T-H appear to be mediated at least in part via PPAR-gamma
      activation, which down-regulates IL-6 and iNOS gene expression in the heart.

PMID- 16794399
TI  - Surgical crisis management skills training and assessment: a
      simulation[corrected]-based approach to enhancing operating room performance.
AB  - BACKGROUND: Intraoperative surgical crisis management is learned in an
      unstructured manner. In aviation, simulation training allows aircrews to
      coordinate and standardize recovery strategies. Our aim was to develop a surgical
      crisis simulation and evaluate its feasibility, realism, and validity of the
      measures used to assess performance. METHODS: Surgical trainees were exposed to a
      bleeding crisis in a simulated operating theater. Assessment of performance
      consisted of a trainee's technical ability to control the bleeding and of their
      team/human factors skills. This assessment was performed in a blinded manner by 2
      surgeons and one human factors expert. Other measures consisted of time measures
      such as time to diagnose the bleeding (TD), inform team members (TT), achieve
      control (TC), and close the laceration (TL). Blood loss was used as a surrogate
      outcome measures. RESULTS: There were considerable variations within both senior
      (n = 10) and junior (n = 10) trainees for technical and team skills. However,
      while the senior trainees scored higher than the juniors for technical skills (P
      = 0.001), there were no differences in human factors skills. There were also
      significant differences between the 2 groups for TD (P = 0.01), TC (P = 0.001),
      and TL (0.001). The blood loss was higher in the junior group. CONCLUSIONS: We
      have described the development of a novel simulated setting for the training of
      crisis management skills and the variability in performance both in between and
      within the 2 groups.

PMID- 16794401
TI  - Leslie Brent and the mysterious German surgeon.

PMID- 16794400
TI  - Postconditioning, a series of brief interruptions of early reperfusion, prevents
      neurologic injury after spinal cord ischemia.
AB  - OBJECTIVE: We sought to test whether postconditioning, a series of brief
      mechanical interruptions of reperfusion applied during the onset of reperfusion,
      can prevent neurologic injury of the spinal cord after transient ischemia.
      SUMMARY BACKGROUND DATA: Ischemia-reperfusion injury of the spinal cord is the
      principal mechanism leading to the paraplegia after surgery for descending and
      thoracoabdominal aortic aneurysms. Postconditioning has recently been
      demonstrated to confer cardioprotection by attenuating reperfusion injury.
      METHODS: Spinal cord ischemia was induced in rabbits by infrarenal aorta
      occlusion for 25 minutes. Control animals underwent no additional intervention.
      Two groups of animals underwent postconditioning consisting of 4 or 6 cycles of 1
      minute occlusion/1-minute reperfusion, respectively, which were applied 1 minute
      after the start of reperfusion. In 2 additional groups, 6 cycles of
      postconditioning started 5 or 10 minutes after the onset of reperfusion,
      respectively. Hind-limb motor function was assessed during a 10-day recovery
      period using the modified Tarlov criteria. Histologic examination of the spinal
      cord was performed, and the number of intact motor neurons was counted. RESULTS:
      Compared with controls, 4 cycles of postconditioning significantly increased the
      Tarlov score and the number of intact motor neurons. Six cycles of
      postconditioning did not further improve the neuroprotection. Postconditioning
      starting 5 minutes after reperfusion still resulted in powerful neuroprotection,
      but the neuroprotection disappeared completely when postconditioning was delayed
      for 10 minutes. CONCLUSIONS: Postconditioning prevents neurologic injury of the
      spinal cord after ischemia, and the first few minutes of reperfusion are crucial
      to neuroprotection by postconditioning.

PMID- 16794403
TI  - Magnetic resonance cholangiography in gallstone pancreatitis.

PMID- 16794405
TI  - Osteomyelitis of the foot and toe.

PMID- 16794407
TI  - Vasal obstruction after hernioplasty: the importance of surgical strategy in
      preventing azoospermia.

PMID- 16794411
TI  - Large pyogenic liver abscess: open surgical drainage for all?

PMID- 16794408
TI  - Non-operative management of pancreatic pseudocysts: there is still a role.

PMID- 16794412
TI  - Systematic appraisal of the role of metallic endobiliary stents in the treatment
      of benign bile duct stricture.

PMID- 16794414
TI  - The role of magnetic resonance imaging in minimal access surgery.
AB  - PURPOSE OF REVIEW: Magnetic resonance imaging is commonly used for gynaecological
      malignancies, but also is increasingly used for the investigation of benign
      gynaecological complaints. This review summarizes the current evidence regarding
      its use as an adjunct to minimal access surgery for endometriosis, adenomyosis,
      adhesions and fibroids. RECENT FINDINGS: Magnetic resonance imaging appears to be
      equal in efficacy to ultrasound for the diagnosis of both fibroids and
      endometriosis, and perhaps superior for the diagnosis of adenomyosis. It is
      extremely useful for the preoperative investigation of severe endometriosis,
      especially recto-vaginal disease. Milder endometriosis is, however, still
      difficult to diagnose by either ultrasound or magnetic resonance imaging.
      Magnetic resonance imaging can also be helpful for the detection of adhesions,
      pelvic collections, congenital defects and fibroids. It is also useful following
      fibroid embolization. SUMMARY: Currently, it is not cost-effective to use
      magnetic resonance imaging as the modality of first choice when investigating
      pelvic pain and or menstrual disorders. If preoperative patients are carefully
      selected, however, it can substantially reduce surgical morbidity by using it to
      diagnose severe endometriosis and adhesions which may lead to cost savings
      overall.

PMID- 16794415
TI  - Endometriosis and assisted reproduction: the role for reproductive surgery?
AB  - PURPOSE OF REVIEW: The aim of this review paper is to discuss the relationship
      between endometriosis and assisted reproductive technology. More specifically,
      the following clinically relevant issues will be discussed. (1) Does the presence
      of endometriosis affect the outcome of assisted reproductive technology? (2) Does
      surgical treatment for endometriosis prior to or after assisted reproductive
      technology treatment affect the outcome of assisted reproductive technology? (3)
      Is assisted reproductive technology a risk factor for the recurrence of
      endometriosis after medical or surgical therapy? RECENT FINDINGS: The review is
      based on recently published review papers/meta-analyses or international
      guidelines as published by the European Society of Human Reproduction or the
      American Society of Reproductive Medicine, updated with a selective review of
      recent papers searching PubMed with the key words 'Endometriosis', 'Assisted
      Reproduction', 'IVF', 'IUI' and 'Reproductive Surgery'. SUMMARY: At the end of
      this review, a practical proposal for the clinical management of women with
      endometriosis-associated subfertility is proposed, based on our own experience.

PMID- 16794416
TI  - A review of total laparoscopic hysterectomy: role, techniques and complications.
AB  - PURPOSE OF REVIEW: The following review examines the current role of total
      laparoscopic hysterectomy, which is a hysterectomy completed entirely
      laparoscopically. Recent advances in equipment, surgical techniques and training
      have made total laparoscopic hysterectomy a well tolerated and efficient
      technique. It is increasingly being adopted around the world because of the
      benefits to patients and surgeons. This study discusses the role of total
      laparoscopic hysterectomy, provides some technical suggestions about how to
      perform a total laparoscopic hysterectomy and how to avoid possible
      complications. RECENT FINDINGS: Only a few surgeons performing total laparoscopic
      hysterectomy have published their techniques and results. The terminology and
      techniques for total laparoscopic hysterectomy used by different surgeons, such
      as energy sources, the use of uterine manipulators, vaginal tubes, the method for
      uterine artery ligation and method of vault closure, vary. This makes objective
      comparison of the literature, techniques and complication rates difficult.
      SUMMARY: As more surgeons become trained in advanced laparoscopic surgery, the
      role of total laparoscopic hysterectomy will increasingly take over indications
      for total abdominal hysterectomy. It remains important that surgeons share their
      experience and publish their techniques, results and complications. Advanced
      laparoscopic training and supervision are paramount before embarking on total
      laparoscopic hysterectomy, so that complications are minimized.

PMID- 16794417
TI  - Laparoscopic Burch colposuspension and the tension-free vaginal tape procedure.
AB  - PURPOSE OF REVIEW: Minimally invasive procedures for urinary incontinence and
      pelvic organ prolapse have gained increasing popularity in the past decade. The
      advantages of minimal access through laparoscopic and vaginal routes include
      smaller incisions, shortened hospital stay, decreased analgesia, rapid recovery
      and rapid return to work. The laparoscopic Burch colposuspension and the tension
      free vaginal tape procedure were at the forefront of minimal access
      antiincontinence procedures. The most recent and significant publications
      regarding laparoscopic Burch colposuspension and tension-free vaginal tape
      procedure are highlighted in this article. RECENT FINDINGS: The laparoscopic
      Burch is time-consuming and requires a steep learning curve in laparoscopic
      suturing, thwarting its adoption and staying power. The advantages and success of
      the retropubic midurethral sling procedures such as tension-free vaginal tape
      have largely replaced all other antiincontinence procedures and have ignited the
      development and adoption of transobturator midurethral sling procedures and
      vaginal 'kit' procedures for pelvic organ prolapse. SUMMARY: Clinical trials show
      that laparoscopic Burch cure rates are equal or inferior to tension-free vaginal
      tape cure rates. Publications regarding laparoscopic Burch colposuspension have
      tapered significantly in the past year, which may represent the ebb of its
      utilization. Tension-free vaginal tape and other midurethral sling procedures may
      become the new 'gold standard' antiincontinence therapy.

PMID- 16794418
TI  - Endometrial ablation in patients with myomas.
AB  - PURPOSE OF REVIEW: This review evaluates how the presence of uterine myomas may
      limit the ability to provide endometrial ablations for patients with menorrhagia,
      affect subsequent postoperative course and alter long-term outcome. RECENT
      FINDINGS: New instrumentation and the off-label use of some global ablation
      techniques allow some selected patients with submucosal myomas to be treated
      solely by endometrial ablation. The addition of an endometrial ablation in
      patients undergoing a hysteroscopic myomectomy improves bleeding and their long
      term control, but does not decrease the subsequent need for a hysterectomy.
      Necrosis of intramural myomas is a rare postoperative complication. Untreated
      myomas may continue to increase in size and lead to a hysterectomy. SUMMARY: The
      presence of myomas in patients undergoing endometrial ablation may compromise the
      results and lead to later problems, but most patients can be treated successfully
      and myomas are not an absolute contraindication.

PMID- 16794419
TI  - Surgical and radiological management of uterine fibroids in the UK.
AB  - PURPOSE OF REVIEW: Uterine fibroids remain the most common benign gynaecological
      pathology and a frequent reason for gynaecological referral and treatment. The
      range of available treatments is currently undergoing a minor revolution with the
      introduction of nonsurgical therapies, but their role remains to be established.
      RECENT FINDINGS: Arguably the most significant change in recent years has been
      the availability of uterine artery embolization as a form of nonsurgical
      management. A survey of UK gynaecologists, however, has shown that the option of
      embolization is only utilized by just over half the respondents. Instead,
      conventional surgery such as hysterectomy and myomectomy remain the mainstay of
      nonsymptomatic treatment. In the absence of gross uterine enlargement, vaginal
      hysterectomy is feasible and safe. Fewer hysterectomies, however, are being done
      and more women are undergoing myomectomy, with almost 50% of UK consultant
      gynaecologists carrying out hysteroscopic myomectomy and just over 10%
      laparoscopic myomectomy. SUMMARY: Greater utilization of less invasive endoscopic
      or vaginal procedures for the management of uterine fibroids seems a reasonable
      target. In the longer term, it is likely that the various nonsurgical techniques
      which shrink fibroids and thereby reduce symptoms will have an increasingly
      important role in the treatment of this common condition.

PMID- 16794420
TI  - Pregnancy outcomes following treatment for fibroids: uterine fibroid embolization
      versus laparoscopic myomectomy.
AB  - PURPOSE OF REVIEW: The management of uterine fibroids in patients requiring
      treatment who desire future fertility remains controversial. Myomectomy has been
      the most common operative procedure to improve pregnancy rates and outcomes.
      Uterine fibroid embolization is an increasingly popular, minimally invasive
      treatment for fibroids. This review aims to provide critical analysis of
      available data on pregnancy following myomectomy and uterine artery embolization.
      RECENT FINDINGS: Patients with distorted uterine cavities due to submucosal
      fibroids of more than 2 cm have higher pregnancy rates following hysteroscopic
      resection. Pregnancy rates following myomectomy, both via laparoscopy and
      laparotomy, are in the 50-60% range, with most having good outcomes. Pregnancy
      rates following uterine artery embolization have not been established.
      Pregnancies following uterine artery embolization had higher rates of preterm
      delivery (odds ratio 6.2, 95% confidence interval 1.4-27.7) and malpresentation
      (odds ratio 4.3, 95% confidence interval 1.0-20.5) than pregnancies following
      laparoscopic myomectomy. SUMMARY: Both myomectomy and uterine artery embolization
      are safe and effective fibroid treatments, which should be discussed with
      appropriate candidates. Pregnancy complications, most importantly preterm
      delivery, spontaneous abortion, abnormal placentation and postpartum hemorrhage,
      are increased following uterine artery embolization compared to myomectomy.
      Although most pregnancies following uterine artery embolization have good
      outcomes, myomectomy should be recommended as the treatment of choice over
      uterine artery embolization in most patients desiring future fertility.

PMID- 16794421
TI  - Laparoscopic staging of early ovarian carcinoma.
AB  - PURPOSE OF REVIEW: A European randomized trial on early stage ovarian cancer
      confirmed the importance of accurate staging to select candidates for adjuvant
      chemotherapy. Since early-stage disease is often discovered incidentally, staging
      is not always carried out or inadequately performed at the time of primary
      surgery. Laparoscopy was reported more than 10 years ago as a method of
      performing the staging procedure while avoiding the morbidity from a classical
      midline incision. RECENT FINDINGS: Several teams have recently published their
      results on laparoscopic staging. Updated results of an earlier series in addition
      to other recent studies are discussed. All highlight the advantages and limits of
      the method. SUMMARY: Complete laparoscopic management seems feasible in selected
      cases of apparently early stage ovarian cancer. Re-staging procedures remain an
      ideal indication for laparoscopy in early adnexal carcinomas. Due to the critical
      nature of the information obtained, this approach should only be reserved for
      teams trained in advanced laparoscopy.

PMID- 16794422
TI  - Psychological and social interventions in the menopause.
AB  - PURPOSE OF REVIEW: Increasingly, menopause research is using knowledge of
      psychological and social functioning to understand women's experiences of
      menopause and develop interventions to treat symptoms or reduce risk factors.
      Clinicians are more aware of the need to take account of psychological processes
      when discussing treatment choices, risks and quality of life. Here, we review the
      most recent developments in this area. RECENT FINDINGS: Group interventions based
      on a cognitive-behaviour therapy approach that address beliefs about symptoms and
      teach specific techniques (paced respiration) can reduce the frequency of hot
      flushes. Studies using a health education framework indicate that information is
      more salient for women when there are given feedback on their own higher
      osteoporosis risk status. Finally, there are promising signs that interventions
      to reduce risk factors can lead to sustained lifestyle change. SUMMARY: The
      increasing interest in psychological and social interventions is reflected in the
      number of new publications, but there are still too few large-scale well
      controlled studies. Earlier work on treatment decision making, and the factors
      predicting treatment choices has not been followed by larger studies. Reported
      research emphasizes the need for clinicians to assess women's beliefs about
      menopausal symptoms and use this knowledge to develop shared treatment plans.

PMID- 16794423
TI  - Premature ovarian failure.
AB  - PURPOSE OF REVIEW: To summarize current knowledge about premature ovarian failure
      (POF) with an emphasis on recent developments regarding its management. RECENT
      FINDINGS: The incidence of POF is increasing largely due to improved survival
      rates of cancer patients treated with radiation and chemotherapy. Delayed
      diagnosis and management of POF leads to suboptimal outcomes. Anticipation and
      early detection of this condition in high-risk women by means of ovarian function
      testing, followed by early institution of appropriate management could improve
      outcomes. Choice of strategies should vary depending on the age of onset,
      associated symptoms and fertility aspirations of the individual, and should
      change with the patient's advancing age. SUMMARY: Early assessment of the
      individual's risk of developing POF, development of a strategic management plan,
      and timely commencement of infertility and hormone deficiency treatment, together
      with counselling in an integrated management plan should improve both the short
      and long-term health of those with POF.

PMID- 16794424
TI  - Androgen and menopause.
AB  - PURPOSE OF REVIEW: Androgen therapy is being increasingly used in the management
      of postmenopausal women. The most common indication is to improve sexual
      function. The aim of this review is to evaluate current knowledge pertaining to
      testosterone and sexual function in postmenopausal women. RECENT FINDINGS: The
      change of testosterone levels during the menopause transition remains
      controversial. A correlation of endogenous testosterone levels and sexual
      function is still inconclusive. A Cochrane Review and recent randomized control
      trials have, however, consistently demonstrated that short-term testosterone
      therapy in combination with traditional hormone therapy regimens improves sexual
      function in postmenopausal women, particularly surgically menopausal women with
      hypoactive sexual desire disorder. An adverse effect on the lipid profile has
      been identified which appears to be mostly associated with oral
      methyltestosterone. Data for other effects of testosterone and long-terms risks
      are lacking. Testosterone may act in a variety of ways in different tissues. This
      is, however, an area that requires further investigation. SUMMARY: Testosterone
      therapy is a promising option for treating women with hypoactive sexual desire
      disorder after surgical menopause. Two remaining questions need to be answer: who
      is most likely to benefit from testosterone therapy and what are the long-term
      health risks?

PMID- 16794425
TI  - Pitfalls in systematic reviews.
AB  - PURPOSE OF REVIEW: The term 'evidence-based medicine' means integrating
      individual clinical expertise with the best available external clinical evidence
      from systematic research. An important source for those who wish to practise
      evidence-based medicine is the systematic review. Systematic reviews, however,
      are not without their pitfalls. This review will consider the problems and
      challenges for researchers and users of systematic reviews. RECENT FINDINGS:
      Failure to adequately assess study quality, funding bias, publication bias,
      reliance on outcomes that provide no help in clinical decision-making, analysis
      errors and the incorrect use of evidence statements are all common pitfalls in
      systematic reviews. SUMMARY: There are several steps in completing a systematic
      review. These include developing the clinical question, searching for all
      available literature, study selection, assessment of study quality, data
      extraction, data analysis, interpreting the results, implications for practice
      and further research, and finally updating the review in a timely manner. Authors
      of systematic reviews need to be aware of these problems and attempt to address
      them so that research evidence may be of clinical value to both providers and
      consumers of healthcare.

PMID- 16794426
TI  - Implantation failure following in-vitro fertilization.
AB  - PURPOSE OF REVIEW: Embryo implantation remains the rate-limiting step in assisted
      conception programmes. Factors affecting the interactions between blastocyst and
      endometrium are subjects of current research and, sadly, have also been the
      subjects of much confusion. This review aims to present current thinking on
      factors affecting embryo development, endometrial receptivity during and around
      the implantation window and the evidence for and against various proposed
      treatment options RECENT FINDINGS: Age-related aneuploidies of the sex
      chromosomes and several other autosomes are now thought to adversely affect
      oocyte and embryo quality, leading to repeat in-vitro fertilization failures.
      Several small controlled trials have suggested improvements in clinical outcomes
      following preimplantation screening and blastocyst transfer for aneuploidy in
      older women. These are, however, very costly, wasteful of embryos and do not
      appear beneficial after the age of 40 years. Factors influencing endometrial
      receptivity remain largely unresolved. New technology using microarrays for gene
      expression profiling and progesterone receptor polymorphism may shed more light
      in the near future. SUMMARY: Giant strides have been made in studying the
      causative factors of implantation failure, but these have not been matched by
      therapeutic solutions. Many proposed interventions are of unproven value, yet can
      have harmful side-effects.

PMID- 16794427
TI  - Infertility and thyroid disorders.
AB  - PURPOSE OF REVIEW: This review highlights the 'gap' in knowledge regarding the
      contribution of thyroid dysfunction in reproduction. Thyroid dysfunction, which
      is quite prevalent in the population affects many organs including the male and
      female gonads, interferes with human reproductive physiology, reduces the
      likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming
      relevant in the algorithm of reproductive dysfunction. RECENT FINDINGS: Although
      menstrual irregularities are common, ovulation and conception can still occur in
      hypothyroidism, where thyroxine treatment restores a normal menstrual pattern and
      reverses hormonal changes. Subclinical hypothyroidism may be associated with
      ovulatory dysfunction and adverse pregnancy outcome. Thyroid autoimmunity
      increases the miscarriage rate, and thyroxine treatment does not seem to protect.
      Menstrual disturbances, frequent in thyrotoxicosis are restored following
      treatment. In males, thyrotoxicosis has a significant but reversible effect on
      sperm motility. Although radioactive Iodine (I) in ablation doses may transiently
      affect the gonads, it does not decrease fertility or increase genetic
      malformation rate in the offspring. SUMMARY: Awareness of the thyroid status in
      the infertile couple is crucial, because of its significant, frequent and often
      reversible or preventable effect on infertility. Many aspects of the role of
      thyroid disorders however in infertility need further research.

PMID- 16794428
TI  - Mind over matter: psychological factors and the menstrual cycle.
AB  - PURPOSE OF REVIEW: Increasingly, gynaecologists are becoming aware of the impact
      of psychosocial factors on women's health generally, and on the menstrual cycle
      in particular. This review highlights developments in this field in the last
      triennium. RECENT FINDINGS: Stress impairs the ovarian cycle through activation
      of the hypothalamus pituitary adrenal axis. The effect of psychological stress on
      the menstrual cycle is mediated by metabolic factors. Stress-induced impairment
      of ovarian function may not necessarily manifest as menstrual irregularity, and
      the effects of stress may persist beyond the cycle in which the stress episode
      occurred. Response to stress may be determined not so much by the nature of the
      stress as by the intrinsic neuronal attributes of the individual. SUMMARY:
      Interventions to address underlying stress should be part of the management
      regime for women with menstrual cycle abnormalities.

PMID- 16794429
TI  - Clinical and health service implications of second generation endometrial
      ablation devices.
AB  - PURPOSE OF REVIEW: This review evaluates the current evidence on the efficacy,
      safety and cost-effectiveness of the ever-increasing number of second-generation
      endometrial ablation devices. RECENT FINDINGS: The literature covered by this
      review includes (1) evidence on long-term benefit, avoidance of hysterectomy and
      improvement in quality of life, (2) applicability of these techniques in the
      outpatient environment under local or no anaesthesia, (3) frequency and nature of
      early and delayed complications associated with these devices, (4) impact on
      clinical practice and the health service, and (5) implications for research.
      SUMMARY: Where appropriate, second-generation devices are rapidly becoming the
      first-line surgical choice for the management of heavy menstrual bleeding. This
      has both cost-savings and negative implications for the health service. There is
      also emerging evidence that improvement in quality of life is more relevant to
      women than amenorrhoea rates. What has come to light from this review is the lack
      of accurate data on adverse events rate, and the urgent need for a better
      appreciation of the frequency and nature of complications.

PMID- 16794430
TI  - Bibliography. Current world literature. Minimally invasive gynecologic
      procedures.

PMID- 16794431
TI  - Uterine contractility and embryo implantation.
AB  - PURPOSE OF REVIEW: The aim of this article is to assess the importance of uterine
      contractility in the implantation of human embryos. RECENT FINDINGS: Recent
      findings show that the receptive phase of the endometrium seems to occur in close
      association with the appearance of pinopodes and endometrial integrins that may
      be activated by the IL-1 system. Throughout the menstrual cycle wavelike activity
      patterns of the uterus were identified with adequate wave patterns appearing to
      be related to successful reproduction in spontaneous cycles and in assisted
      reproduction. Such patterns are controlled by steroid hormones. Embryo attachment
      to the predecidualized endometrium and its invasion may be determined by the
      expression of proteolytic enzymes that require uterine quiescence for
      implantation. The uterine activity was detected both in vitro and in vivo by
      using invasive intrauterine pressure and noninvasive ultrasound approaches.
      Progesterone promotes local vasodilatation and uterine musculature quiescence by
      inducing nitric oxide synthesis in the decidua. At present, until new evidence
      emerges to demonstrate otherwise, the effects of progesterone are, directly or
      indirectly, the only determinant of endometrial preparation for embryo nidation,
      with the induction of uterine quiescence being one of these effects. SUMMARY:
      Adequate uterine contractility may provide for gamete/embryo transportation
      through the utero-tubal cavities and successful embryo implantation in
      spontaneous or assisted reproduction. Inadequate uterine contractility may lead
      to ectopic pregnancies, miscarriages, retrograde bleeding with dysmenorrhea and
      endometriosis.

PMID- 16794432
TI  - 56,000 Ways? No way!

PMID- 16794433
TI  - Update on utilities and cost-utility analyses.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the recent and
      noteworthy utility studies and cost-utility analyses in the area of
      retina/vitreous during the period January 2004 to January 2006. RECENT FINDINGS:
      This review considers the cost-effectiveness of treatments for wet age-related
      macular degeneration, dry age-related macular degeneration, telemedicine in
      diabetic retinopathy, and utilities and patients with age-related macular
      degeneration and diabetic retinopathy. SUMMARY: Utilities are being used
      increasingly to measure health-related quality of life. Cost-utility analyses are
      becoming more readily available for comparing the incremental cost-effectiveness
      of different ophthalmic interventions.

PMID- 16794434
TI  - Basic understanding of current classification and management of retinoblastoma.
AB  - PURPOSE OF REVIEW: The current classification and management strategies for
      retinoblastoma are discussed. RECENT FINDINGS: The International Classification
      of Retinoblastoma is a new classification system for retinoblastoma and is based
      on tumor size, location, and associated seeding: group A = retinoblastoma up to 3
      mm in size; group B = retinoblastoma more than 3 mm in size, macular location, or
      minor subretinal fluid; group C = retinoblastoma with localized seeds; group D =
      retinoblastoma with diffuse seeds; and group E = massive retinoblastoma
      necessitating enucleation. This classification was designed to simplify grouping
      and to assist in predicting treatment outcomes. Chemoreduction is an important
      therapy for bilateral retinoblastoma and some cases of unilateral retinoblastoma.
      This International Classification of Retinoblastoma can reliably predict
      chemoreduction outcome, as success was achieved in 100% of group A, 93% of group
      B, 90% of group C, and 47% of group D cases. Group E is typically managed with
      enucleation. SUMMARY: The new classification of retinoblastoma allows better
      judgement for success with chemoreduction for retinoblastoma.

PMID- 16794435
TI  - The use of intravitreal corticosteroids, evidence-based and otherwise.
AB  - PURPOSE OF REVIEW: To provide a current update on the use of intravitreal
      corticosteroids as a treatment for a variety of retinal diseases. RECENT
      FINDINGS: Pharmacokinetic studies demonstrate that a single 4 mg injection of
      intravitreal triamcinolone acetonide is present in the vitreous for up to 3
      months. Many recent studies demonstrate a significant reduction in macular edema
      often with a significant improvement in vision for up to several months followed
      by a waning of treatment effect and recurrence of macular edema. Retreatments
      have been shown to be efficacious. Intravitreal triamcinolone acetonide may help
      lead to a reduction in subfoveal hard exudates in diffuse diabetic macular edema.
      It has been shown to be a more potent treatment than sub-Tenon's and retrobulbar
      triamcinolone acetonide for persistent macular edema. It may also be a
      significant adjunctive treatment for choroidal neovascularization treated with
      photodynamic therapy. Intravitreal corticosteroid implants have also been shown
      to be beneficial in early trials for persistent macular edema. SUMMARY:
      Intravitreal triamcinolone acetonide provides a potent short-term treatment for
      persistent macular edema and may be a useful adjunctive treatment for choroidal
      neovascularization. It remains to be determined whether intravitreal
      corticosteroids can provide long-term visual gain or stabilization. The side
      effect profile of intravitreal corticosteroids is significant with corticosteroid
      induced intraocular pressure rises. With longer-term studies, the rate of
      posterior subcapsular cataract formation is higher than previously reported, and
      there is a small but potential risk of endophthalmitis.

PMID- 16794436
TI  - Primary retinal detachment: scleral buckle or pars plana vitrectomy?
AB  - PURPOSE OF REVIEW: There remains no consensus among vitreoretinal surgeons
      regarding the optimal management of primary rhegmatogenous retinal detachment. In
      this article, fundamental principles are discussed and applied to recent clinical
      reports. RECENT FINDINGS: The consensus of the peer-reviewed literature appears
      to be that scleral buckling and primary pars plana vitrectomy may yield
      comparable single-operation success rates and visual acuity outcomes for a wide
      variety of rhegmatogenous retinal detachments. SUMMARY: No definitive
      prospective, randomized, multicenter trial compares scleral buckling with pars
      plana vitrectomy. The upcoming Scleral Buckling versus Primary Vitrectomy in
      Rhegmatogenous Retinal Detachment study may yield useful information in this
      regard. Even when this study is completed, the choice of surgical modality is
      complex and may be individualized for specific patients.

PMID- 16794437
TI  - Management of choroidal metastases from breast carcinomas using aromatase
      inhibitors.
AB  - PURPOSE OF REVIEW: The outcome of patients diagnosed with uveal metastases from
      breast carcinoma, all of whom were treated with one of the new generation of
      hormone therapies named aromatase inhibitors, is reported. RECENT FINDINGS:
      Charts of all patients with uveal metastases from breast cancer seen at Wills Eye
      Hospital between 1995 and 2005 are reviewed. Seventeen patients were diagnosed
      with uveal metastases from estrogen-receptor-positive breast cancer and
      subsequently treated with one of the aromatase inhibitors (anastrozole,
      letrozole, exemestane). SUMMARY: The interval between initial diagnosis of breast
      cancer and choroidal metastases ranged from 1 month to 17 years. Thirteen
      patients had received tamoxifen either at the time of breast surgery or as part
      of the metastases treatment. In 10 cases, both the systemic and choroidal
      metastases remained regressed over a mean of 20 months follow-up (4-50 months).
      There was no toxicity or intolerance to the medication. Aromatase inhibitors
      represent a new generation of hormone therapy for metastatic breast cancer. They
      were effective in 59% of the patients with estrogen-receptor-positive breast
      cancer, many of them nonresponding to prior treatment with tamoxifen. Aromatase
      inhibitors avoid the need for external beam radiation therapy as a treatment for
      the ocular metastases.

PMID- 16794438
TI  - The burden of age-related macular degeneration: a value-based analysis.
AB  - PURPOSE OF REVIEW: The quality-of-life loss and the financial consequences
      associated with age-related macular degeneration are assessed. RECENT FINDINGS:
      The quality-of-life loss associated with macular degeneration is markedly
      underestimated by the general public, nonophthalmic physicians, and
      ophthalmologists who treat patients with this condition. Mild age-related macular
      degeneration causes a 17% decrement in the quality of life of the average
      patient, similar to that encountered with moderate cardiac angina or symptomatic
      human immunodeficiency virus syndrome. Moderate age-related macular degeneration
      causes a 40% decrease in the average patient's quality of life, similar to that
      associated with severe cardiac angina or renal dialysis. Very severe age-related
      macular degeneration causes a large 63% decrease in the average patient's quality
      of life, similar to that encountered with end-stage prostatic cancer or a
      catastrophic stroke that leaves a person bedridden, incontinent and requiring
      constant nursing care. The return on investment is high for both treatment with
      current age-related macular degeneration therapies and the research costs
      invested in the development of age-related macular degeneration treatment
      modalities. SUMMARY: Age-related macular degeneration is a major public health
      problem that has a devastating effect upon patients and marked adverse financial
      consequences for the economy.

PMID- 16794440
TI  - The Charles Bonnet syndrome: a review of recent research.
AB  - PURPOSE OF REVIEW: The Charles Bonnet syndrome is a disorder of visual
      hallucinations typically occurring in older persons with vision impairment or
      deafferentation of the visual cortex. This review cites recent studies on Charles
      Bonnet syndrome and discusses treatment options. The numbers of affected persons
      will increase with aging of the population, making recognition and treatment
      important components of ophthalmologic care. RECENT FINDINGS: The etiology of the
      Charles Bonnet syndrome is varied; most often it involves direct damage to the
      visual system (e.g. age-related macular degeneration, glaucoma) but it may also
      result from cerebral pathology interrupting connections between the eye and the
      occipital cortex. Case reports of different management approaches demonstrate the
      range of treatment options. SUMMARY: This review suggests that the Charles Bonnet
      syndrome will affect an increasingly large number of older persons as the
      population ages and the occurrence of vision and cerebral disorders increases.
      Clinical trials of antipsychotic and other medications, as well as low-vision
      rehabilitation, are necessary to establish valid treatments for this disorder.

PMID- 16794439
TI  - Treatment of nonexudative (dry) age-related macular degeneration.
AB  - PURPOSE OF REVIEW: The purpose of this report is to review the recent literature
      and summarize currently available and potential new treatment options for
      nonexudative age-related macular degeneration. RECENT FINDINGS: High-dose vitamin
      supplementation may have some associated systemic toxicity. It is important to
      check that the patient is taking beta-carotene and not vitamin A as retinal
      acetate or palmitate, which have been associated with osteoporosis and
      hepatotoxicity. High-dose vitamins E and C may be associated with cardiovascular
      disease. Decreasing inflammation by lowering systemic cardiac C-reactive protein,
      fibrinogen and cholesterol may be important, especially in light of recent
      epidemiologic and genetic data. The results of randomized trials of laser
      treatment for drusen and rheopheresis should be available during 2006. Treatment
      with these modalities before the results of the trials are evaluated should be
      avoided. SUMMARY: The holy grail of therapy for age-related macular degeneration
      is to avoid the development of choroidal neovascularization. High-dose vitamin
      supplementation should be used only in those in whom it is indicated and
      inflammatory parameters including highly sensitive C-reactive protein, fibrinogen
      and cholesterol should be stabilized because there are data associating these
      parameters with age-related macular degeneration and also with cardiovascular
      disease.

PMID- 16794441
TI  - New evidence that vision rehabilitation is a key component in the management of
      patients with macular degeneration.
AB  - PURPOSE OF REVIEW: Vision rehabilitation has been considered as an adjunct
      support option or just the dispensing of magnifiers in the management of macular
      degeneration. RECENT FINDINGS: New research suggests that vision rehabilitation
      can cause physical changes in the brain that help patients adjust to permanent
      vision loss. SUMMARY: Vision rehabilitation is related to physical changes that
      occur in the brain. Its use in conjunction with clinical low-vision programs may
      pave the way for developing better rehabilitation techniques for patients with
      macular blindness.

PMID- 16794442
TI  - Diabetic vitrectomy: risks, prognosis, future trends.
AB  - PURPOSE OF REVIEW: We review the current standards, risks, prognosis, and
      indications for diabetic pars plana vitrectomy and consider recent developments
      in surgical techniques. We also examine surgery's role as a treatment modality
      for diabetic eye disease among the other accepted and developing treatment
      options, such as systemic and intravitreal pharmacotherapy. RECENT FINDINGS: Pars
      plana vitrectomy for diabetic macular edema and for traction retinal detachment
      is addressed. Techniques to decrease retinal swelling and ischemia are showing
      promising results. The use of the smaller 25-gauge and 23-gauge vitrectors is
      gaining acceptance and offers advantages such as less trauma, less postoperative
      discomfort, and quicker healing. Techniques are being developed and refined to
      help prevent postoperative vitreous hemorrhage using cryotherapy around
      sclerotomy sites and/or endolaser in a near-confluent pattern in an effort to
      quell fibrovascular ingrowth and subsequent hemorrhage. Finally, pharmacological
      advances include targeting three levels of intervention: achieving the best
      glycemic control, correcting altered retinal metabolism secondary to increased
      glucose availability, and employing neuroprotective and vasoprotective agents.
      SUMMARY: The combination of therapies and interventions as they improve and
      evolve offers the potential to revolutionize the approach to the complications of
      diabetic eye disease and may soon render many current interventions obsolete.
      Diabetic pars plana vitrectomy continues to advance with better anatomic and
      visual success.

PMID- 16794443
TI  - Endophthalmitis: a reappraisal of incidence and treatment.
AB  - PURPOSE OF REVIEW: The current publications that address either the incidence or
      treatment of endophthalmitis are reviewed. RECENT FINDINGS: A large body of
      published research has recently addressed the issue of potential increases in the
      incidence of endophthalmitis, especially postcataract endophthalmitis. Additional
      studies have evaluated relatively new antibiotics and their potential effect on
      the prevention and treatment of endophthalmitis. SUMMARY: Although there appears
      to be a renewed effort to report the incidence and theorized risk factors for
      postcataract endophthalmitis, there are wide discrepancies in the rate and
      potential causes of postoperative endophthalmitis. In regards to endophthalmitis
      treatment, helpful findings regarding the potency of newer antibiotics and the
      appropriateness of subconjunctival antibiotics are reviewed.

PMID- 16794444
TI  - Pain and suffering disability index.
AB  - PURPOSE OF REVIEW: This report summarizes the increasing financial resources
      required to deal with personal injury tort cases and medical malpractice. The
      largest single component in personal injury torts is noneconomic damages, which
      encompasses 'pain and suffering' and punitive damage, the latter of which
      comprises only a small percentage. Overall, noneconomic damages account for 24%
      of the greater than US$250 billion spent annually on personal injury torts.
      RECENT FINDINGS: A pain and suffering disability index has been developed that
      quantifies the loss of life's value attributable to personal injury. Based upon
      time-tradeoff utility analysis, the value loss is predicated upon the values of
      people who have experienced the same degree of disability or injury as the
      plaintiff, only outside the courtroom environs. It is believed that the pain and
      suffering disability index will readily identify frivolous, personal injury
      torts, decrease the number of frivolous, personal injury torts, markedly decrease
      the variance of noneconomic tort settlements, facilitate the earlier settlement
      of personal injury tort cases, and decrease the proportion of personal injury
      tort cases progressing to jury trial. SUMMARY: The pain and suffering disability
      index is a novel instrument that quantifies the 'pain and suffering' associated
      with a personal injury tort according to the values of patients who have
      experienced a similar injury outside the courtroom environs.

PMID- 16794445
TI  - Bibliography. Current world literature. Retinal, vitreous and macular disorders.

PMID- 16794446
TI  - Hypertension, the Kuna, and the epidemiology of flavanols.
AB  - A low sodium diet has often been implicated in the protection of low blood
      pressure populations from hypertension, but several other dietary factors,
      including those as yet unidentified, may also be involved. The Kuna Indians of
      Panama are free of hypertension and cardiovascular disease, but this is changing
      with migration to urban areas. We compared the indigenous diet of Kuna Indians
      living on remote islands in Panama (Ailigandi), whose lifestyle is largely hunter
      gatherer, with those who have moved to a suburb of Panama City (Vera Cruz).
      Between April and October 1999, members of a Kuna research team administered a
      118-item food frequency questionnaire to133 adult Kuna from Ailigandi and 183
      from Vera Cruz. Single 24-hour urine collections and nonfasting blood samples
      were obtained. The Kuna in Ailigandi reported consuming a 10-fold higher amount
      of cocoa-containing beverages, 4 times the amount of fish, and twice the amount
      of fruit as urban Kuna (P<0.05 by t test). Salt added was ample among those
      living in Ailigandi and Vera Cruz according to both self-report (7.1+/-1.1 and
      4.6+/-0.3 tsp weekly) and urinary sodium levels (177+/-9 and 160+/-7 mEq Na/g
      creatinine), respectively. The low blood pressure of island-dwelling Kuna does
      not seem to be related to a low salt diet. Among dietary factors that varied
      among migrating Kuna, the notably higher intake of flavanol-rich cocoa is a
      potential candidate for further study.

PMID- 16794447
TI  - Analysis of flavanols in foods: what methods are required to enable meaningful
      health recommendations?
AB  - Flavanols and their related oligomeric compounds, the procyanidins, have received
      increased attention during the past decade due to their reported health benefits.
      On the basis of compelling data published during the past decade demonstrating
      that the consumption of certain flavanol-rich foods can improve markers of
      cardiovascular health, additional clinical, and epidemiological research is
      clearly warranted to establish appropriate public health recommendations.
      However, recommendations on the consumption of these foods appropriate for use by
      health professionals can only be made on the basis of clinical investigations
      that accurately identify and quantify--through proper analytical measurement
      systems--the flavanols in the foods used in these investigations. This manuscript
      provides an overview of the strengths, weaknesses, and limitations of commonly
      used analytical methods to characterize the content of flavanols in foods. Two
      nonspecific measurements widely used by investigators, the Folin-Ciocalteu assay
      and the Oxygen Radical Absorbance Capacity (ORAC) measurement, are discussed in
      this context, as is the use of various high-performance liquid chromatography
      methods that provide more specific data related to the content of flavanols in
      foods. A comparison of the data obtained from these analytical methods to those
      of the more rigorous high-performance liquid chromatography analyses demonstrates
      that these nonspecific methods are ill-suited for providing unequivocal data
      necessary to evaluate the importance of dietary flavanols in the context of
      improving cardiovascular health. Meaningful dietary recommendations for the
      consumption of flavanol-rich foods will only be made possible by additional well
      designed clinical and epidemiological studies enabled by detailed compositional
      data obtained through use of appropriate analytical methods.

PMID- 16794449
TI  - Flavanols and cardiovascular health: effects on the circulating NO pool in
      humans.
AB  - Atherosclerosis is the major cause for chronic vascular diseases. The key event
      in the pathogenesis of atherosclerosis is believed to be dysfunction of the
      endothelium and disruption of endothelial homeostasis, leading to
      vasoconstriction, inflammation, leukocyte adhesion, thrombosis, and proliferation
      of vascular smooth muscle cells. Endothelium-derived nitric oxide (NO) plays a
      major role in vascular homeostasis and a decrease in NO-bioavailability
      accelerates the development of atherosclerosis. Given that endothelial
      dysfunction is at least in part reversible, the characterization of endothelial
      function and therapeutical approaches have gained much attention over the past
      years. Recent studies demonstrated that especially the consumption of plant
      derived foods rich in certain flavonoids can improve endothelial function in both
      compromised and healthy humans. Furthermore, various physiologic and biochemical
      measures have been used previously as biomarkers for the assessment of the
      proposed beneficial effects of flavonoids in this context. More recently, the
      analysis of plasma nitros(yl)ated species (RXNOs), referred to as the circulating
      NO pool, has gained recognition, especially as a marker for endothelial function.
      This review is aimed at evaluating the suitability of quantifying this NO pool as
      a biomarker for cardiovascular function in humans, in particular during dietary
      interventions with flavonoid-rich foods.

PMID- 16794450
TI  - Endothelial function, nitric oxide, and cocoa flavanols.
AB  - Endothelial dysfunction is the pathophysiologic principle involved in the
      initiation and progression of arteriosclerosis, thus endothelial function serves
      as a "barometer" for cardiovascular health that can be used for the evaluation of
      new therapeutic strategies. This review provides an introduction to the concept
      of endothelial dysfunction, and it explores the importance of this prognostic
      marker in the context of clinical, dietary interventions in humans. Moreover, we
      summarize and evaluate the findings of various clinical trials that demonstrated
      an improvement of endothelial dysfunction in subjects with cardiovascular risk
      factors after the acute and chronic consumption of flavanol-rich foods, including
      cocoa products, red wine, and tea.

PMID- 16794451
TI  - Protection of endothelial function: targets for nutritional and pharmacological
      interventions.
AB  - The vascular endothelium synthesizes and releases a spectrum of vasoactive
      substances and therefore plays a fundamental role in the basal and dynamic
      regulation of the circulation. Nitric oxide (NO)-originally described as
      endothelium-derived relaxing factor-is released from endothelial cells in
      response to shear stress produced by blood flow, and in response to activation of
      a variety of receptors. After diffusion from endothelial to vascular smooth
      muscle cells, NO increases intracellular cyclic guanosine-monophosphate
      concentrations by activation of the enzyme guanylate cyclase leading to
      relaxation of the smooth muscle cells. NO has also antithrombogenic,
      antiproliferative, leukocyte-adhesion inhibiting effects, and influences
      myocardial contractility. Endothelium-derived NO-mediated vascular relaxation is
      impaired in spontaneously hypertensive animals. NO decomposition by free oxygen
      radicals is a major mechanism of impaired NO bioavailability. The resulting
      imbalance of endothelium-derived relaxing and contracting substances disturbs the
      normal function of the vascular endothelium. Endothelin acts as the natural
      counterpart to endothelium-derived NO. Besides its arterial blood pressure rising
      effect in humans, endothelin-1 induces vascular and myocardial hypertrophy, which
      are independent risk factors for cardiovascular morbidity and mortality. Current
      therapeutic strategies concentrate mainly on lowering low-density lipoprotein
      cholesterol and an impressive reduction in the risk for cardiovascular morbidity
      and mortality has been achieved. Inflammatory mechanisms play an important role
      in vascular disease and inflammatory plasma markers correlate with prognosis. The
      production of reactive oxygen species under pathological conditions may represent
      an important inflammatory trigger. Novel therapeutic strategies specifically
      targeting inflammation thus bear great potential for the prevention and treatment
      of atherosclerotic vascular disease. In this context, the vascular actions of
      flavanol-rich cocoa, particularly with regard to enhanced NO synthesis and
      endothelial function observed in humans following consumption, warrants further
      attention. This review discusses pharmacological and dietary intervention.

PMID- 16794452
TI  - Microalbuminuria and endothelial dysfunction: emerging targets for primary
      prevention of end-organ damage.
AB  - A minor increase in urinary albumin excretion (microalbuminuria) is known to
      predict adverse renal and cardiovascular events in diabetic and hypertensive
      patients. Recent intriguing findings show that microalbuminuria is an early and
      sensitive marker of future cardiovascular events even in healthy subjects. The
      mechanisms linking microalbuminuria with end-organ damage have not been fully
      explained yet; however, generalized endothelial dysfunction might play an
      important role. Prevailing experimental and clinical data suggest that
      generalized endothelial dysfunction, frequently characterized by decreased nitric
      oxide bioavailability, actually precedes the development of microalbuminuria.
      This review summarizes the current knowledge about the intricate relationship
      between microalbuminuria and endothelial dysfunction. On the basis of the current
      evidence, we propose that microalbuminuria and endothelial dysfunction are an
      emerging target for primary prevention strategies in cardiovascular disease. In
      near future, dietary components improving nitric oxide bioavailability, such as
      cocoa-derived flavanols may play important role in these preventive strategies.

PMID- 16794453
TI  - The anti-inflammatory properties of cocoa flavanols.
AB  - Signs of chronic or acute inflammation have been demonstrated in most
      cardiovascular diseases of multifactorial pathogenesis, including atherosclerosis
      and chronic heart failure. The triggers and mechanisms leading to inflammation
      may vary between clinical conditions but they share many common mediators,
      including specific patterns of eicosanoid and cytokine production. Certain cocoa
      based products can be rich in a subclass of flavonoids known as flavanols, some
      of which have been found in model systems to possess potential anti-inflammatory
      activity relevant to cardiovascular health. Indeed, experimental evidence
      demonstrates that some cocoa-derived flavanols can reduce the production and
      effect of pro-inflammatory mediators either directly or by acting on signaling
      pathways. However, it should be noted that the evidence for any beneficial
      effects of cocoa flavanols in providing a meaningful anti-inflammatory action has
      been gathered predominantly from in vitro experiments. Therefore, additional
      research in well-designed human clinical experiments, using cocoa properly
      characterized in terms of flavanol content, would be a welcome addition to the
      evidence base to determine unambiguously if this benefit does indeed exist. If
      so, then flavanol-rich cocoa could be a potential candidate for the treatment, or
      possibly prevention, of the broad array of chronic diseases that are linked to
      dysfunctional inflammatory responses.

PMID- 16794456
TI  - Chronic consumption of flavanol-rich cocoa improves endothelial function and
      decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal
      women.
AB  - Endothelial dysfunction characterizes many disease states including subclinical
      atherosclerosis. The consumption of flavanol-rich cocoa and cocoa-based products
      has been shown to improve endothelial function in both compromised and otherwise
      normal, healthy individuals when administered either acutely or over a period of
      several days, or weeks. Women experience increased risk for cardiovascular
      disease after menopause, which can be associated with endothelial dysfunction.
      Whether a flavanol-rich cocoa-based product can improve endothelial function in
      hypercholesterolemic postmenopausal women is not known. The purpose of the
      present study was to determine whether chronic dietary administration of flavanol
      rich cocoa improves endothelial function and markers of cardiovascular health in
      hypercholesterolemic postmenopausal women. Thirty-two postmenopausal
      hypercholesterolemic women were randomly assigned to consume a high-flavanol
      cocoa beverage (high cocoa flavanols (CF)--446 mg of total flavanols), or a low
      flavanol cocoa beverage (low CF--43 mg of total flavanols) for 6 weeks in a
      double-blind study (n=16 per group). Endothelial function was determined by
      brachial artery-reactive hyperemia. Plasma was analyzed for lipids (total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol), hormones (follicle-stimulating hormone), total nitrate/nitrite,
      activation of cellular adhesion markers (vascular cell adhesion molecule 1,
      intercellular adhesion molecule 1, E-Selectin, P-Selectin), and platelet function
      and reactivity. Changes in these plasma markers were then correlated to brachial
      reactivity. Brachial artery hyperemic blood flow increased significantly by 76%
      (P<0.05 vs. baseline) after the 6-week cocoa intervention in the high CF group,
      compared with 32% in the low CF cocoa group (P=ns vs. baseline). The 2.4-fold
      increase in hyperemic blood flow with high CF cocoa closely correlated (r2=0.8)
      with a significant decrease (11%) in plasma levels of soluble vascular cell
      adhesion molecule-1. Similar responses were not observed after chronic use of low
      CF. There were no significant differences between high and low CF in other
      biochemical markers and parameters measured. This study is the first to identify
      beneficial vascular effects of flavanol-rich cocoa consumption in
      hypercholesterolemic postmenopausal women. In addition, our results suggest that
      reductions in plasma soluble vascular cell adhesion molecule-1 after chronic
      consumption of a flavanol-rich cocoa may be mechanistically linked to improved
      vascular reactivity.

PMID- 16794457
TI  - Dietary flavanols and platelet reactivity.
AB  - Epidemiology studies suggest that the consumption of diets rich in flavonoids is
      associated with reduced risk of cardiovascular disease. Plant-derived foods and
      beverages, such as red wine, tea, grape and grape juice, cocoa and chocolate, can
      be rich in 1 particular class of flavonoid, the flavan-3-ols. There is now an
      increasing body of research that suggests that consuming flavanol-rich foods can
      positively affect hemostasis, through mechanisms that either directly affect
      platelet function or increase certain endothelium-derived factors that maintain
      platelet acquiescence or increase fibrinolysis. In this paper, we will review a
      series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on
      platelet activation and platelet-dependent hemostasis. In addition, we will
      briefly review the body of literature with regard to other flavanol-rich foods
      and beverages, and possible mechanisms of action.

PMID- 16794458
TI  - Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo
      studies in healthy adults.
AB  - There is growing interest in possible beneficial effects of specific dietary
      components on cardiovascular health. Platelets and leukocytes contribute to
      arterial thrombosis and to inflammatory processes. Previous studies performed in
      vitro have demonstrated inhibition of platelet function by (-)-epicatechin and
      (+)-catechin, flavan-3-ols (flavanols) that are present in several foods
      including some cocoas. Also, some modest inhibition of platelet function has been
      observed ex vivo after the consumption of flavanol-containing cocoa products by
      healthy adults. So far there are no reports of effects of cocoa flavanols on
      leukocytes. This paper summarizes 2 recent investigations. The first was a study
      of the effects of cocoa flavanols on platelet and leukocyte function in vitro.
      The second was a study of the effects of consumption of a flavanol-rich cocoa
      beverage by healthy adults on platelet and leukocyte function ex vivo.
      Measurements were made of platelet aggregation, platelet-monocyte conjugate
      formation (P/M), platelet-neutrophil conjugate formation (P/N), platelet
      activation (CD62P on monocytes and neutrophils), and leukocyte activation (CD11b
      on monocytes and neutrophils) in response to collagen and/or arachidonic acid. In
      the in vitro study several cocoa flavanols and their metabolites were shown to
      inhibit platelet aggregation, P/M, P/N, and platelet activation. Their effects
      were similar to those of aspirin and the effects of a cocoa flavanol and aspirin
      did not seem to be additive. There was also inhibition of monocyte and neutrophil
      activation by flavanols, but this was not replicated by aspirin. 4'-O-methyl
      epicatechin, 1 of the known metabolites of the cocoa flavanol (-)-epicatechin,
      was consistently effective as an inhibitor of platelet and leukocyte activation.
      The consumption of a flavanol-rich cocoa beverage also resulted in significant
      inhibition of platelet aggregation, P/M and P/N, and platelet activation induced
      by collagen. The inhibitory effects were related to their flavanol content. There
      was also inhibition of monocyte and neutrophil activation, but here it was
      concluded that cocoa constituents other than flavanols may contribute to the
      inhibition that was observed. It can be concluded that cocoa flavanols, their
      metabolites and possibly other cocoa constituents can modulate the activity of
      platelets and leukocytes in vitro and ex vivo. The research suggests that the
      consumption of certain cocoa products may provide a dietary approach to
      maintaining or improving cardiovascular health.

PMID- 16794460
TI  - Cocoa flavanols and brain perfusion.
AB  - Foods and beverages rich in flavonoids are being heralded as potential preventive
      agents for a range of pathologic conditions, ranging from hypertension to
      coronary heart disease to stroke and dementia. We and others have demonstrated
      that short-term ingestion of cocoa, particularly rich in the subclass of
      flavonoids known as flavanols, induced a consistent and striking peripheral
      vasodilation in healthy people, improving endothelial function in a nitric oxide
      dependent manner. The vasodilator response was reversed by N-nitro-L-arginine
      methyl ester, an arginine analog that blocks nitric oxide synthesis. Flavanol
      poor cocoa induced much smaller responses. Because impairment of endothelial
      function is a nearly universal accompaniment of the aging process, we examined
      the peripheral vasodilator response to flavanol-rich cocoa in healthy older
      subjects. Observations point to a favorable response among the older. Together
      with peripheral vascular disease, cerebrovascular disease is responsible for
      significant mortality with advancing age. An association of decreased cerebral
      perfusion with dementia has been recently highlighted. The prospect of increasing
      cerebral perfusion with cocoa flavanols is extremely promising. Our still
      preliminary data hold out the promise that the cerebral blood supply in the
      elderly participates in the vasodilator response. With the modalities of
      transcranial Doppler and MRI, we have the capabilities of analyzing the potential
      benefits of flavanols on brain perfusion and, subsequently, on cognition.

PMID- 16794461
TI  - The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in
      healthy young people.
AB  - Flavanols are the main flavonoids found in cocoa and chocolate, and can be
      especially abundant in certain cocoas. Research over the past decade has
      identified flavanols as showing diverse beneficial physiologic and antioxidant
      effects, particularly in context of vascular function. The present study employed
      functional magnetic resonance imaging based on blood oxygenation level-dependent
      (BOLD) contrast to explore the effect of flavanols on the human brain. Magnetic
      resonance imaging was used to measure BOLD responses to a cognitive task in 16
      healthy young subjects. The data presented show an increase in the BOLD signal
      intensity in response to a cognitive task following ingestion of flavanol-rich
      cocoa (5 days of 150 mg of cocoa flavanols). This may arise either as a result of
      altered neuronal activity, or a change in vascular responsiveness, or both--the
      net effect then being dependent on which of the two effects is dominant. No
      significant effects were evident in behavioral reaction times, switch cost, and
      heart rate after consumption of this moderate dose of cocoa flavanols. A pilot
      study evaluated the relationship between cerebral blood flow and a single acute
      dose (450 mg flavanols) of flavanol-rich cocoa and showed that flavanol-rich
      cocoa can increase the cerebral blood flow to gray matter, suggesting the
      potential of cocoa flavanols for treatment of vascular impairment, including
      dementia and strokes, and thus for maintaining cardiovascular health.

PMID- 16794462
TI  - Cocoa flavanols, cerebral blood flow, cognition, and health: going forward.

PMID- 16794463
TI  - Vascular action of cocoa flavanols in humans: the roots of the story.
AB  - Diet patterns are widely recognized as contributors to hypertension. Widely
      studied potential contributors include intake of sodium, potassium, magnesium,
      calcium, soluble fiber, omega-3 fatty acids, alcohol, protein, and calories. We
      add to that list the effect of dietary flavanols present in certain cocoas, which
      have sufficient activity on vascular nitric oxide to influence blood pressure
      control. Kuna Indians who live on islands near Panama have little age-related
      rise in blood pressure or hypertension. On migration to Panama City, blood
      pressure rises with age, and the frequency of essential hypertension matches
      urban levels elsewhere. We have identified a specific food that probably makes an
      important contribution to cardiovascular status. Island-dwelling Kuna drink more
      than 5 cups of flavanol-rich cocoa per day and incorporate that cocoa into many
      recipes. Mainland Kuna ingest little cocoa, and what they take is commercially
      available and flavanol-poor. The flavanol-rich cocoa activates nitric oxide
      synthase in vitro and in intact humans in the doses that the Kuna employ.
      Vasodilator responses to flavonoid-rich cocoa are prevented or reversed by the
      arginine analog, N-nitro-L-arginine methyl ester. Island-dwelling Kuna have a 3
      fold larger urinary nitrate:nitrite than do Mainland dwellers. As endothelial
      dysfunction is central to current thinking on cardiovascular pathophysiology, a
      food that enhances endothelial function could have broad implications. The list
      of candidate conditions that might be influenced is impressive, ranging from
      atherosclerosis and diabetes mellitus to hypertension and preeclampsia, to
      vascular dementias and end-stage renal disease. The next decade will be
      interesting.

PMID- 16794466
TI  - The assessment of left ventricular hypertrophy in hypertension.
AB  - The presence of left ventricular hypertrophy (LVH) in hypertension, as detected
      by the electrocardiogram or echocardiography, is associated with an increased
      risk of mortality and morbidity several times above and beyond the risk of
      hypertension alone. The LIFE (Losartan Intervention For Endpoint reduction in
      hypertension) study confirmed that pharmacological agents, which reduce LVH,
      confer further reduction in morbidity and mortality. This makes the
      identification of patients with LVH all the more important. In this article we
      describe the various methods available to diagnose the presence of LVH in
      patients with hypertension, and consider their strengths and their place in
      clinical practice and in research.

PMID- 16794467
TI  - Estimation of an age-specific reference interval for pulse wave velocity: a meta
      analysis.
AB  - OBJECTIVE: To estimate an age-specific reference interval for carotid-femoral
      pulse wave velocity (PWV), an index of aortic stiffness, and to determine the
      predictive values of the reference range for detecting those at moderate and high
      risk of cardiovascular disease (CVD). DESIGN AND METHODS: We searched MEDLINE
      using PubMed from 1995 to 2005 for all studies in which Carotid-Femoral PWV was
      measured using a Complior (Colson, Paris, France) apparatus in Caucasian non
      pregnant adults. Twenty-five studies were included, covering 30 groups of
      subjects; these groups were classified a priori into low (normal), moderate, and
      high CVD risk categories, with 2008, 5979, and 180 (total 8167) subjects,
      respectively. Individual-level data were simulated for each group, and an age
      specific reference interval was calculated by using fractional polynomial
      functions. RESULTS: We plotted an age-adjusted normal curve for PWV with 2.5, 5,
      50, 90, 95, and 97.5 centile limits. Applying this reference interval to the
      moderate- and high-risk groups using simulations yielded sensitivities of 34.3
      [95% confidence interval (CI) 33.2-35.3] and 57.2 (95% CI 55.2-59.3),
      respectively, specificities of 95.3 (95% CI 94.8-95.8) and 95.3 (95% CI 94.4
      96.2), respectively, and positive likelihood ratios of 7.3 and 12.2,
      respectively. CONCLUSION: We constructed an age-adjusted reference curve for PWV.
      Using the 95th centile of this curve as a threshold (e.g. 10.94, 11.86, and 13.18
      m/s for 20, 40, and 60 years old) shows construct validity, as it appears to
      identify medium and high CVD risk groups reasonably accurately. This reference
      range needs to be tested using other datasets.

PMID- 16794468
TI  - Activity, environment and blood pressure.

PMID- 16794469
TI  - Aging and hypertension: what about the endothelium?

PMID- 16794470
TI  - Can adult cardiovascular disease be programmed in utero?

PMID- 16794471
TI  - Blood pressure and stroke: a continuing debate.

PMID- 16794472
TI  - Antagonistic modulation of vascular tone by Rho-kinase and nitric oxide: new
      insights into the mechanisms of blood pressure control.

PMID- 16794473
TI  - Gender differences in the relation between number of teeth and systolic blood
      pressure.
AB  - BACKGROUND: Tooth loss predicts total and circulatory mortality. The reasons for
      the increased mortality in subjects with a low number of teeth may be related to
      enhanced atherosclerosis, elevated arterial pressure and more frequent
      hypertension. The present study was designed to investigate whether there is an
      association between the number of teeth and arterial pressure or hypertension.
      METHODS: We used data of 4185 adult subjects (2150 women) collected for the
      population-based Study of Health in Pomerania. The number of teeth was counted by
      trained and certified dentists. Hypertension was defined as systolic blood
      pressure >or= 140 mmHg or diastolic blood pressure >or= 90 mmHg or use of
      antihypertensive medication. Multivariable analyses were adjusted for relevant
      confounders. RESULTS: The adjusted mean (standard error) systolic blood pressure
      in men having 0-6 teeth was 149.6 mmHg (1.3 mmHg) compared to 142.6 mmHg (1.2
      mmHg) in men having 27-28 teeth (P < 0.05). The adjusted odds for hypertension in
      men with 0-6 teeth compared to men with 27-28 teeth were 1.91 (95% confidence
      interval 1.21; 3.02, P < 0.05). In women no such relations were found.
      CONCLUSION: There is an inverse association between the number of teeth and
      systolic blood pressure and hypertension in men but not in women. The present
      findings partly explain the relation between tooth loss and mortality.

PMID- 16794474
TI  - Benefit of home blood pressure measurement after a finding of high blood pressure
      at a community screening.
AB  - OBJECTIVE: Many hypertensive individuals are not under medical management. We
      studied whether incorporating home blood pressure measurement and subsequent
      tailored advice into the primary care system improved hypertension management
      among untreated hypertensive individuals (screening systolic blood pressure >or=
      140 mmHg or diastolic blood pressure >or= 90 mmHg and not taking antihypertensive
      medication) diagnosed during a community screening. METHODS: All residents aged
      30 years or older in one district were asked to measure their blood pressure at
      home for 30 days, then received tailored advice (intervention area). Four of five
      Japanese districts served as a control. A self-administered questionnaire
      monitored the awareness and treatment of hypertension. RESULTS: Eighty-eight per
      cent (106/120) of untreated hypertensive individuals in the intervention area
      measured home blood pressure. Of men and women meeting the criteria for untreated
      hypertension at a community screening in 2003, 97 intervention and 390 control
      individuals were rescreened in 2004. Among the untreated 2003 screening
      hypertensive individuals with home hypertension (home systolic blood pressure
      >or= 135 mmHg or diastolic blood pressure >or= 85 mmHg), the proportion not
      starting antihypertensive medication was 56%, and the proportion taking 'no
      action against hypertension' was 41%. These proportions were lower than in the
      control group (76%, 60%), yielding odds ratios (95% confidence interval) of 0.38
      (0.21-0.68) and 0.42 (0.24-0.75), respectively. CONCLUSION: Incorporating home
      blood pressure measurement coupled with tailored advice into the primary care
      system has the potential to reduce the risk of untreated hypertension.

PMID- 16794475
TI  - Infradian awake and asleep systolic and diastolic blood pressure rhythms in
      humans.
AB  - BACKGROUND: Blood pressure shows 24-h rhythms with a significant seasonal
      fluctuation. OBJECTIVES: To characterize 2-month to 12-month infradian rhythms in
      the mean awake and asleep systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) in humans. METHODS: A total of 1689 participants underwent 24-h
      ambulatory blood pressure monitoring during different periods of the year. The
      mean daily temperature, humidity, barometric pressure and wind velocity values
      for the same time span and geographical location were obtained. Fourier analysis
      was used to fit 12-month, 6-month, 4-month, 3-month and 2-month rhythms to the
      mean awake and asleep SBP and DBP and to metereological variables. RESULTS: The
      awake mean SBP and DBP values showed significant 12-month and 3-month rhythms
      (respectively, R2 = 55%, P < 0.001 and R2 = 45% P < 0.001), with a peak in July
      (winter) and a trough-peak difference of 6.2 +/- 1.6 mmHg (P < 0.001, SBP) and
      4.2 +/- 1.5 mmHg (P < 0.001, DBP). In contrast, asleep blood pressure means
      showed mainly 3-month rhythms (SBP, R2 = 19%, P < 0.02; DBP, R2 = 43% P < 0.02).
      Mean daily temperature and humidity showed at 12-month, 6-month, 4-month, 3-month
      and 2-month rhythms, barometric pressure showed 12-month and 6-month rhythms, and
      wind velocity showed 12-month and 3-month rhythms. Minimal temperature values and
      maximal humidity values coincided with elevated blood pressure values.
      CONCLUSION: Awake blood pressure means exhibited mainly circannual fluctuations
      while asleep blood pressure means showed principally 3-month rhythms. Infradian
      blood pressure variations correlated with some meteorological variables.

PMID- 16794476
TI  - Predicting cardiovascular risk using creatinine clearance and an artificial
      neural network in primary hypertension.
AB  - OBJECTIVE: A slight reduction in estimated creatinine clearance is a predictor of
      unfavorable outcome in patients with primary hypertension. We evaluated how well
      an artificial neural network (ANN) can assess cardiovascular risk profile on the
      basis of estimated creatinine clearance and routine, low-cost clinical data, as
      compared with thorough clinical work-up, which includes an accurate assessment of
      target organ damage. METHODS: A group of 404 untreated patients with essential
      hypertension (250 men, 154 women; mean age, 47 +/- 9 years) were studied. We
      compared two different approaches that can be used to allocate patients into
      different risk classes according to the European Society of Hypertension-European
      Society of Cardiology guidelines: thorough clinical work-up, including cardiac
      and vascular ultrasound scan and microalbuminuria; and prediction by an ANN on
      the basis of estimated creatinine clearance and routine clinical data. RESULTS:
      Thorough evaluation, as recommended by the guidelines, showed that 6% (n = 24) of
      our patients were at low risk, 20% (n = 81) were at medium risk, 45% (n = 182)
      were at high risk, and 29% (n = 117) were at very high risk. The ANN approach
      yielded almost superimposable results (sensitivity, 94%; positive predictive
      value, 96%; r = 0.95). CONCLUSIONS: An ANN can accurately identify the patient's
      risk status using low-cost, clinical data and estimated creatinine clearance.
      These results emphasize the value of even a mild reduction in creatinine
      clearance for the stratification of cardiovascular risk in primary hypertension.

PMID- 16794477
TI  - Combined acute effects of red wine consumption and cigarette smoking on
      haemodynamics of young smokers.
AB  - OBJECTIVE: Red wine seems to improve haemodynamic variables, while smoking
      provokes adverse effects. The haemodynamic effects of their combined use is
      unknown. The purpose of the present study was to examine the acute effects of red
      wine and its constituents, in combination with the smoking of one cigarette, on
      haemodynamic parameters, such as blood pressure and wave reflections, in a group
      of smokers. METHODS: Twenty smokers (12 males, eight females) participated in a
      double-blind, crossover study comprised of 3 study days. All subjects either
      smoked one cigarette, or smoked and drank 250 ml of red wine, or 250 ml of de
      alcoholized red wine (containing the same type and similar concentration of
      antioxidants). Applanation tonometry and generalized transfer functions were used
      to estimate aortic pressure waveforms at baseline and 30, 60 and 90 min after
      each trial. The augmentation index (AIx) was used to express wave reflections.
      RESULTS: Smoking increased peripheral systolic blood pressure (P < 0.005) 30 min
      later, but simultaneous consumption of either type of red wine caused no such
      effect. Additionally, smoking caused no overall effect on AIx, while smoking and
      drinking either regular or de-alcoholized red wine reduced AIx (P < 0.001). The
      reduction of AIx after red wine consumption was significantly greater than the
      respective reduction after de-alcoholized red wine (P = 0.004). CONCLUSION:
      Antioxidant substances in red wine counteracted the smoking-induced increase in
      peripheral systolic blood pressure. Both alcohol and antioxidants in red wine
      decrease wave reflections in uncomplicated habitual smokers postprandially,
      indicating an additional favourable effect of red wine.

PMID- 16794478
TI  - The PON1192RR genotype is associated with a higher prevalence of arterial
      hypertension.
AB  - OBJECTIVE: To investigate whether genetic polymorphism of paraoxonase (PON1192),
      an enzyme which protects low density lipoprotein from oxidation, is related to
      the prevalence of arterial hypertension. METHODS: Two groups of carefully
      selected subjects of both sexes were enrolled and compared. The first group
      comprised 219 healthy controls (mean age 46.5 +/- 14.7 years) whereas the second
      comprised 119 hypertensive patients (mean age 47.9 +/- 10.5 years) with untreated
      essential arterial hypertension. Anthropometric and biochemical parameters were
      within the normal range in both groups. The PON1192 polymorphism was determined
      by a polymerase chain reaction-restriction fragment length polymorphism approach.
      RESULTS: In hypertensive patients, a significant increase of the frequency of
      PON1192RR genotype with respect to healthy controls (14.3 versus 5.0%, P = 0.003)
      was found. Logistic regression analyses also showed that the PON1192RR genotype
      was independently associated with a four-fold increase in susceptibility to
      arterial hypertension (odds ratio = 4.31; 95% confidence interval = 1.63-11.43, P
      = 0.003). CONCLUSIONS: The finding that PON1192RR genotype is associated with a
      higher prevalence of arterial hypertension may contribute to improving the
      stratification of cardiovascular risk within a population aged 30-60 years.
      Determination of the PON1192 polymorphism may help to identify those individuals
      who are prone to developing cardiovascular diseases at an early stage, suggesting
      the need for close monitoring of cardiovascular risk factors before the onset of
      cardiovascular disease.

PMID- 16794479
TI  - The C242T CYBA polymorphism of NADPH oxidase is associated with essential
      hypertension.
AB  - OBJECTIVE: Oxidative stress is implicated in hypertension. The reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the main source
      of superoxide in phagocytic and vascular cells. The C242T polymorphism of CYBA,
      the human gene that encodes p22phox, has been found to be functionally associated
      with vascular NADPH oxidase activity in atherosclerotic patients. We investigated
      the association of the C242T polymorphism with hypertension and its potential
      impact on NADPH oxidase activity. We also analysed the interaction of C242T
      polymorphism with the -930A/G CYBA variant. DESIGN: Case-control study in a
      random sample of 623 subjects (326 hypertensive patients and 297 normotensive
      controls) from the general population. METHODS: CYBA polymorphisms were
      determined by restriction fragment length polymorphism (RFLP) or allelic
      discrimination. NADPH oxidase activity and p22phox expression were quantified in
      phagocytic cells by chemiluminescence and by northern and western blots,
      respectively. RESULTS: The prevalence of the CC genotype and the C allele
      frequency were significantly higher (P < 0.05) in hypertensives than in
      normotensives. CC genotype remained associated with hypertension after adjusting
      for potential confounders in a logistic regression analysis. Increased phagocytic
      NADPH oxidase activity was observed in CC hypertensives compared with CT and TT
      hypertensives (P < 0.05). Enhanced plasma levels of von Willebrand factor were
      found in CC hypertensives compared with TT hypertensives (P < 0.05). The C242T
      polymorphism was not in linkage disequilibrium with the -930A/G CYBA promoter
      variation, which also associates with hypertension. CONCLUSION: The C242T CYBA
      polymorphism is associated with essential hypertension. Furthermore,
      hypertensives carrying the CC genotype of this polymorphism exhibit features of
      NADPH oxidase-mediated oxidative stress and endothelial damage.

PMID- 16794480
TI  - Deregulated expression of monocyte chemoattractant protein-1 (MCP-1) in arterial
      hypertension: role in endothelial inflammation and atheromasia.
AB  - OBJECTIVE: Arterial hypertension is recurrently associated with inflammation of
      the endothelium as an effect of the upregulation of functional molecules,
      including cytokines, adhesion molecules and chemokines. However, the role of
      monocyte chemoattractant protein-1 (MCP-1) in maintaining the inflammatory state
      of endothelial cells (EC) that leads to the progressive cardiovascular damage is
      unclear. DESIGN: Here, we investigated the expression of MCP-1, its major cell
      source as well as recurrence of a defined polymorphism (-2518 MCP-1) apparently
      linked to endothelial damage in several diseases. METHODS: Serum MCP-1 was
      measured by enzyme-linked immunosorbent assay (ELISA) in 740 hypertensive
      patients, subdivided according to their individual organ damage. Expression of
      both MCP-1 and its receptor CCR2 was evaluated in circulating ECs and macrophages
      by flow cytometry and real-time reverse transcriptase-polymerase chain reaction
      (RT-PCR), while gene variants of MCP-1 were revealed by PCR. RESULTS: Soluble MCP
      1 was significantly elevated in patients with diffuse atheromasia. Furthermore,
      it was overexpressed by ECs activated to attract macrophages via the MCP-1/CCR2
      pathway, whereas the -2518 MCP-1 polymorphism was correlated with atherosclerosis
      in most patients. CONCLUSIONS.: Overexpression of MCP-1 is predominant in
      hypertensive patients with atheromasia in the form of a defined polymorphism.
      Measurement of MCP-1 may thus reflect the degree of endothelial damage, while
      early detection of such a polymorphism may acquire a prognostic value in the
      development of atherosclerosis.

PMID- 16794481
TI  - Systolic and diastolic hypertension impair endothelial vasodilatory function in
      different types of vessels in the elderly: the Prospective Investigation of the
      Vasculature in Uppsala Seniors (PIVUS) study.
AB  - BACKGROUND: Endothelium-dependent vasodilation (EDV) is known to be impaired in
      middle-aged hypertensive individuals, but less is known regarding hypertension in
      the elderly. OBJECTIVE: In the Prospective Study of the Vasculature in Uppsala
      Seniors (PIVUS) study, different techniques to evaluate EDV in resistance and
      conduit arteries were applied in elderly subjects and were related to the type of
      hypertension. DESIGN AND METHODS: In this population-based study, 1016 subjects
      aged 70 years were evaluated by the invasive forearm technique with acetylcholine
      (EDV), brachial artery ultrasound to assess flow-mediated dilatation (FMD) and
      pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. Those
      without antihypertensive treatment were divided into three groups: normotensive
      individuals (n = 256), and those with isolated systolic hypertension (n = 309) or
      combined systolic/diastolic hypertension (n = 79). RESULTS: Compared with
      normotensive individuals, EDV was reduced in those with combined
      systolic/diastolic hypertension only (P = 0.0019), whereas FMD was mainly reduced
      in those with isolated systolic hypertension (P = 0.013). Furthermore, in
      regression analysis, EDV was related to diastolic blood pressure only (r = -0.10,
      P = 0.017), whereas FMD was mainly related to systolic blood pressure (r = -0.13,
      P = 0.0023). The pulse wave-based method to analyse vasoreactivity was not
      consistently affected by hypertension. CONCLUSIONS: In elderly subjects, systolic
      hypertension mainly impairs conduit artery endothelial vasodilatory function,
      whereas diastolic hypertension mainly induces dysfunction in resistance arteries.

PMID- 16794482
TI  - Regular aspirin use and retinal microvascular signs: the Blue Mountains Eye
      Study.
AB  - OBJECTIVE: Hypertension is closely related to microvascular abnormalities and
      there is increasing interest in agents that target the microvasculature. The
      effect of aspirin on the microvasculature has not been well studied. We examined
      the cross-sectional and longitudinal associations between regular aspirin use and
      retinal microvascular signs. DESIGN AND METHODS: We digitized retinal photographs
      from participants of the Blue Mountains Eye Study cohort (1992-1994, n = 3654,
      aged over 49 years, and 1997-1999, n = 2335) and used a computer-assisted method
      to measure average retinal arteriolar and venular diameters. Information on the
      frequency of aspirin use was collected, with regular aspirin use defined as
      weekly or daily. RESULTS: Regular aspirin users comprised 21.2% (n = 775) of the
      baseline population. At baseline and in individuals who were on one or more
      antihypertensive medication, regular aspirin use was found to be associated with
      retinal arterioles on average 3.6 mum (95% confidence interval 1.0, 6.2) wider
      than those of non-users or occasional aspirin users, after adjusting for age,
      blood pressure, smoking, diabetes, non-steroidal anti-inflammatory drug use and
      other variables. Increasing frequency of aspirin use was associated with
      increasing retinal arteriolar diameter (Ptrend < 0.01). At 5-year follow-up,
      regular users of aspirin and antihypertensive medication(s) had wider retinal
      arterioles than those who used aspirin less regularly. Neither antihypertensive
      medication use alone nor aspirin use alone was associated with wider retinal
      vessels. CONCLUSION: Our finding of a possible association between the combined
      use of aspirin and antihypertensive agent(s) and wider retinal arteriolar
      diameter warrants further investigation into the effects of aspirin on the
      microvasculature.

PMID- 16794483
TI  - Intrauterine growth restriction increases blood pressure and central pulse
      pressure measured with telemetry in aging rats.
AB  - OBJECTIVES: Intrauterine growth restriction (IUGR) is associated with a higher
      risk of hypertension in adulthood. In Western countries, IUGR is based on
      uteroplacental dysfunction. We hypothesize that aging augments the increased
      baseline blood pressure after IUGR and alters the cardiovascular response to
      acute stress. METHODS: To evaluate blood pressure during aging in the rat, we
      used a model of uteroplacental dysfunction (bilateral uterine artery ligation).
      Blood pressure was measured in male offspring at the ages of 6, 9, and 12 months
      using telemetry, allowing for unstressed measurements in conscious animals. At 6
      and 12 months of age, cardiovascular data were obtained during acute olfactory
      stress induced by ammonia and subsequent recovery. RESULTS: Rats born after IUGR
      had lower birth weights (4.6 versus 6.5 g, P < 0.001) and did not completely
      catch up in weight by 12 months of age (519 versus 567 g, P < 0.01). Systolic
      blood pressure was significantly higher in IUGR animals at all ages. Pulse
      pressure (PP) was identical in both groups at the age of 6 months. However, PP
      increased in the IUGR group with increasing age, unlike the control group, and
      was significantly higher at 9 and 12 months of age. At the age of 12 months,
      there was a highly significant negative correlation between birth weight and PP
      (r = -0.82, P < 0.001). IUGR rats reached a higher peak in systolic blood
      pressure during stress, and showed a longer period for the raised heart rate to
      recover after stress. CONCLUSIONS: IUGR is associated with raised baseline blood
      pressure, an increasing PP with age, and an altered stress response.

PMID- 16794484
TI  - Functional reactivity of 5-HT receptors in human umbilical cord and maternal
      subcutaneous fat arteries after normotensive or pre-eclamptic pregnancy.
AB  - OBJECTIVE: To investigate the functional reactivity of 5-hydroxytryptamine
      (serotonin; 5-HT) receptors in foetal umbilical cord arteries (UCA) and maternal
      subcutaneous fat resistance arteries (SFA) in normotensive and pre-eclamptic
      pregnancy. DESIGN: Study groups were divided based on the presence or absence of
      pre-eclampsia and the duration of gestation. METHODS: Segments of UCA and SFA
      were mounted in tissue baths and concentration-response curves to 5-HT and
      sumatriptan (5-HT1B/1D receptor agonist) were constructed in the absence or
      presence of ketanserin (5-HT2A receptor antagonist) or GR125743 (5-HT1B/1D
      receptor antagonist). RESULTS: Both 5-HT and sumatriptan contracted all UCA
      segments studied. The responses to 5-HT and the potency of ketanserin in UCA were
      not different between the study groups, indicating a similar profile of the 5
      HT2A receptor. In contrast, the potencies of sumatriptan and GR125743 were
      significantly higher in normotensive full-term pregnancies than in normotensive
      pre-term pregnancies in UCA. The response to sumatriptan in UCA arteries was not
      significantly different between pre-eclamptic and normotensive pregnancies.
      However, the potency of both sumatriptan and GR125743 was positively correlated
      to the gestational age in the normotensive group, whereas this relationship was
      absent in the pre-eclamptic group. In SFA, responses to 5-HT and sumatriptan were
      not different between the pre-eclamptic patients and normotensive controls.
      CONCLUSIONS: In both UCA and SFA, 5-HT1B/1D and 5-HT2A receptors mediate
      vasoconstriction. The sensitivity of 5-HT1B/1D receptors increases in the last
      trimester in the UCA in normal pregnancies, which seems to be expedited in pre
      eclamptic patients. Further studies on 5-HT1B/ID receptors will thus give new
      insights into the foetal development and pathophysiology of pre-eclampsia.

PMID- 16794485
TI  - Carvedilol-induced antagonism of angiotensin II: a matter of alpha1-adrenoceptor
      blockade.
AB  - OBJECTIVE: To investigate whether renin-angiotensin system blockade might
      underlie the favorable metabolic effects of the nonselective beta + alpha1
      adrenoceptor blocker carvedilol as compared with the selective beta1-adrenoceptor
      blocker metoprolol. METHODS: Human coronary microarteries (HCMAs), obtained from
      32 heart valve donors, were mounted in myographs. RESULTS: Angiotensin II and the
      alpha1-adrenoceptor agonist phenylephrine constricted HCMAs to maximally 63 +/-
      10 and 46 +/- 15% of the contraction to 100 mmol/l K. Neither carvedilol,
      metoprolol, the nonselective beta-adrenoceptor antagonist propranolol, nor the
      alpha1-adrenoceptor antagonist prazosin affected the constrictor response to
      angiotensin II. alpha1-adrenoreceptors and beta-adrenoceptors are thus not
      involved in the direct constrictor effects of angiotensin II. When added to the
      organ bath at a subthreshold concentration, angiotensin II greatly amplified the
      response to phenylephrine. Both carvedilol and the angiotensin II type 1 (AT1)
      receptor antagonist irbesartan inhibited this angiotensin II-induced
      potentiation. Furthermore, carvedilol blocked the angiotensin II-induced
      amplification of phenylephrine-induced inositol phosphate accumulation in
      cardiomyocytes. CONCLUSIONS: AT1-alpha1-receptor crosstalk, involving inositol
      phosphates, sensitizes HCMAs to alpha1-adrenoceptor agonists. Our results suggest
      that, in the presence of an increased sympathetic tone, carvedilol provides AT1
      receptor blockade via its alpha1-adrenoceptor blocking effects. This could
      explain the favorable effects of carvedilol versus metoprolol.

PMID- 16794486
TI  - Angiotensin II induces vascular dysfunction without exacerbating blood pressure
      elevation in a mouse model of menopause-associated hypertension.
AB  - BACKGROUND: Follitropin-receptor knockout (FORKO) mice are estrogen-deficient,
      hyperandrogenic and exhibit features of menopause and elevated blood pressure
      (BP). Because the renin-angiotensin system has been implicated in menopause
      associated hypertension, we questioned whether angiotensin II (Ang II) challenge
      would further increase BP in FORKO mice and whether this is associated with
      cardiovascular remodeling and inflammation. RESULTS: Ang II (400 ng/kg per min)
      increased BP, assessed by radiotelemetry, similarly in female FORKO and wild-type
      (WT) mice. Acetylcholine-induced vasodilation was attenuated and Ang II-induced
      contraction was enhanced in FORKO mice (P < 0.05). This was associated with
      increased expression of vascular Ang type 1 receptors (AT1R) and estrogen
      receptor alpha (ERalpha). Vascular structure (media/lumen ratio) was similar in
      both groups. Abundance of gp91, nitrotyrosine formation and superoxide
      production, indices of inflammation and cardiac collagen content were increased
      in Ang II-treated FORKO compared to Ang II-treated WT mice (P < 0.05).
      CONCLUSIONS: Thus, in FORKO mice Ang II exacerbates endothelial dysfunction,
      augments contractility, increases oxidative stress, and promotes cardiac fibrosis
      without worsening vascular remodeling or BP elevation compared to Ang II-treated
      WT controls. Our findings suggest that in FORKO mice Ang II may be more important
      in influencing vascular tone and endothelial function, possibly through oxidative
      stress and altered ERalpha signaling, than in arterial remodeling and BP
      elevation.

PMID- 16794487
TI  - Evolution of blood pressure and cholesterol in stage 1 hypertension: role of
      autonomic nervous system activity.
AB  - OBJECTIVE: Controversy remains concerning the pathogenetic mechanisms for the
      relationship between sympathetic activity, hypertension and lipid abnormalities.
      We tested the hypothesis that a condition characterized by sympathetic
      predominance may affect the evolution of blood pressure and lipids in the early
      stage of hypertension. METHODS: We prospectively studied 163 young stage 1
      hypertensive individuals and 28 normotensive control individuals. The
      hypertensive subjects were divided by cluster analysis into two groups according
      to low frequency and high frequency components of heart rate variability. Large
      artery and small artery compliance was assessed at the end of the follow-up.
      RESULTS: Fifty-nine subjects showed reduced total power and signs of sympathetic
      predominance in the resting condition, on standing and during mental stress
      (group 1). At baseline, they had similar blood pressure and metabolic data to the
      rest of the group (n = 104, group 2) and a greater white-coat effect (P = 0.03).
      During a 6-year follow-up, 23.7% of group 1 subjects versus 9.6% of group 2
      subjects developed sustained hypertension requiring antihypertensive treatment (P
      = 0.02). In group 1 subjects, there was also a greater increase in total
      cholesterol (P = 0.01) than in group 2. In addition, at the end of follow-up
      group 1 subjects had impaired large artery compliance (P < 0.001 versus group 2).
      CONCLUSIONS: These data indicate that a condition characterized by sympathetic
      predominance may favour the development of sustained hypertension and
      hypercholesterolemia early in life, and lead to increased susceptibility to
      vascular complications. They further indicate that the increased white-coat
      effect is not an innocent phenomenon.

PMID- 16794488
TI  - Mechanism of lipid enhancement of alpha1-adrenoceptor pressor sensitivity in
      hypertension.
AB  - OBJECTIVE AND DESIGN: Plasma lipids enhance alpha1-adrenoceptor pressor
      sensitivity, impair baroreflex function, and correlate with increased blood
      pressure. This clinical study was designed to determine whether the enhanced
      alpha1-pressor sensitivity induced by acute hyperlipidemia is primarily mediated
      by increased vascular alpha1 responsiveness, reduced baroreflex sensitivity (BRS)
      or both. METHOD: Regional alpha1-adrenoceptor vasoreactivity was measured using a
      graded brachial artery infusion of the alpha1 agonist, phenylephrine, in seven
      subjects with stage 1 hypertension. Forearm blood flow was estimated from venous
      occlusion plethysmography. The phenylephrine dose-forearm blood flow response
      curve was used to determine alpha1-vascular reactivity (slope of the dose
      response curve) and sensitivity, EC50 (phenylephrine dose inducing 50% maximal
      response). BRS (ms/mmHg) was measured as the slope of the progressive rise in
      systolic blood pressure and the resultant lengthening in the subsequent R-R
      interval after systemic intravenous boluses of phenylephrine. Subsequently,
      plasma lipids were raised with a 1-h systemic co-infusion of intralipid and
      heparin, after which measurements of regional vasoreactivity and BRS were
      repeated. RESULTS: Mean arterial pressure was 109 +/- 4 versus 110 +/- 3 (P =
      NS), vasoreactivity was -0.71 +/- 0.10 versus -0.82 +/- 0.10 (P = NS) and log
      EC50 was 1.47 +/- 0.29 versus 1.52 +/- 0.34 nmol/l (P = NS) before and after
      raising non-esterified fatty acids, respectively. In contrast, mean BRS was
      acutely reduced from 8.2 +/- 2.1 to 6.2 +/- 1.8 ms/mmHg (P = 0.02) after the
      lipid infusion. CONCLUSIONS: These findings suggest that in hypertensive
      patients, the primary mechanism for short-term alpha1-pressor hypersensitivity in
      response to hyperlipidemia is via the acute impairment of BRS.

PMID- 16794489
TI  - Chronic central nervous system hyperinsulinemia and regulation of arterial
      pressure and food intake.
AB  - BACKGROUND AND OBJECTIVE: Acute studies suggest that insulin has anorexic and
      hypertensive actions through direct effects on the central nervous system (CNS).
      However, the importance of these actions in the long-term regulation of food
      intake and cardiovascular function is still unclear. The goal of the present
      study was to determine whether chronic increases in CNS levels of insulin, in the
      absence of changes in plasma insulin concentration, decrease food intake and
      raise arterial pressure in rats. METHODS: An intracerebroventricular cannula was
      placed in the lateral ventricle of male Sprague-Dawley rats for chronic insulin
      or vehicle (artificial cerebrospinal fluid, 0.5 mul/h) infusion, via osmotic
      minipump, and arterial and venous catheters were implanted for measurement of
      mean arterial pressure (MAP) and heart rate (HR) 24 h/day and intravenous
      infusions. After 4 days of control measurements, insulin (6 mU/h, n = 7 or 12
      mU/h, n = 6) or vehicle (n = 4) was infused intracerebroventricularly for 7 days.
      RESULTS: Insulin infusion at 6 or 12 mU/h caused transient decreases in food
      intake, but did not significantly alter plasma glucose or insulin concentrations.
      Insulin intracerebroventricular infusion also did not alter MAP or HR (106 +/- 2
      and 105 +/- 5 versus 104 +/- 2 mmHg in control; 411 +/- 9 and 407 +/- 9 versus
      410 +/- 7 bpm in control, respectively). Food intake, MAP and HR remained
      unchanged in the vehicle-treated group. CONCLUSIONS: These findings provide no
      evidence that insulin plays a major role in the long-term regulation of appetite,
      arterial pressure or HR. However, the CNS actions of insulin may exert modest
      acute effects on appetite that could play a role in limiting meal size and
      influencing caloric balance.

PMID- 16794490
TI  - Influence of nebivolol and enalapril on metabolic parameters and arterial
      stiffness in hypertensive type 2 diabetic patients.
AB  - OBJECTIVE: To compare the effects of a cardioselective beta-blocker (nebivolol)
      with those of an angiotensin-converting enzyme inhibitor (enalapril) on
      parameters of insulin sensitivity, peripheral blood flow and arterial stiffness
      during one extended glucose clamp experiment. DESIGN: A randomized, double-blind
      crossover trial, consisting of two 12-week treatment phases separated by a 4-week
      wash-out phase. METHODS: Patients with type 2 diabetes and arterial hypertension
      were randomly assigned to one of two treatment sequences (nebivolol-enalapril,
      enalapril-nebivolol). Haemodynamic, metabolic and other laboratory measurements
      were carried out on the first and last day of each treatment period by means of a
      glucose clamp experiment that also involved the measurement of blood flow and
      arterial stiffness. RESULTS: Twelve patients were included in this study, of
      which two dropped out early. Efficacy parameters were therefore available for 10
      patients. There was no significant difference in any of the primary efficacy
      parameters. Moreover, the effects on blood pressure did not significantly differ
      between both treatments. Six adverse events happened during treatment with
      nebivolol compared with two during treatment with enalapril, but only one was
      regarded as possibly related to the treatment. CONCLUSIONS: This pilot study
      shows that the combined measurement of insulin sensitivity, blood flow and
      arterial stiffness is feasible. Nebivolol and enalapril did not show different
      effects with regard to these parameters in hypertensive diabetic patients. If
      these results are confirmed in larger clinical trials, this would argue against
      the reservations against beta-blockers as drugs of first choice in patients with
      diabetes because of potential metabolic side-effects.

PMID- 16794491
TI  - Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high
      risk hypertensive patients: the VALUE trial.
AB  - CONTEXT: Type 2 diabetes is emerging as a major health problem, which tends to
      cluster with hypertension in individuals at high risk of cardiovascular disease.
      OBJECTIVE: To test for the first time the hypothesis that treatment of
      hypertensive patients at high cardiovascular risk with the angiotensin-receptor
      blocker (ARB) valsartan prevents new-onset type 2 diabetes compared with the
      metabolically neutral calcium-channel antagonist (CCA) amlodipine. DESIGN: Pre
      specified analysis in the VALUE trial. Follow-up averaged 4.2 years. The risk of
      developing new diabetes was calculated as an odds ratio (OR) with 95% confidence
      intervals (CI) for different definitions of diabetes. PATIENTS: A sample of 9995
      high-risk, non-diabetic hypertensive patients. INTERVENTIONS: Valsartan or
      amlodipine with or without add-on medication [hydrochlorothiazide (HCTZ) and
      other add-ons, excluding other ARBs, angiotensin-converting enzyme (ACE)
      inhibitors, CCAs]. MAIN OUTCOME MEASURE: New diabetes defined as an adverse
      event, new blood-glucose-lowering drugs and/or fasting glucose > 7.0 mmol/l.
      RESULTS: New diabetes was reported in 580 (11.5%) patients on valsartan and in
      718 (14.5%) patients on amlodipine (OR 0.77, 95% CI 0.69-0.87, P < 0.0001). Using
      stricter criteria (without adverse event reports) new diabetes was detected in
      495 (9.8%) patients on valsartan and in 586 (11.8%) on amlodipine (OR 0.82, 95%
      CI 0.72-0.93, P = 0.0015). CONCLUSION: Compared with amlodipine, valsartan
      reduces the risk of developing diabetes mellitus in high-risk hypertensive
      patients.

PMID- 16794492
TI  - Relationship between outcome and baseline blood pressure and other haemodynamic
      measures in acute ischaemic stroke: data from the TAIST trial.
AB  - BACKGROUND: A poor outcome after stroke is associated independently with high
      blood pressure during the acute phase; however, relationships with other
      haemodynamic measures [heart rate (HR), pulse pressure (PP), rate-pressure
      product (RPP)] remain less clear. METHODS: The Tinzaparin in Acute Ischaemic
      Stroke Trial is a randomised, controlled trial assessing the safety and efficacy
      of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke.
      Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR measurements
      taken immediately prior to randomization were averaged, and the mid-blood
      pressure (MBP), PP, mean arterial pressure (MAP), pulse pressure index, and RPP
      were calculated. The relationship between these haemodynamic measures and
      functional outcome (death or dependency, modified Rankin Scale > 2) and early
      recurrent stroke, were studied with adjustment for baseline prognostic factors
      and treatment group. Odds ratios (OR) and 95% confidence intervals (CI) refer to
      a change in haemodynamic measure by 10 points. RESULTS: A poor functional outcome
      was associated with SBP (adjusted OR; 1.11; 95% CI, 1.03-1.21), HR (adjusted OR;
      1.15; 95% CI, 1.00-1.31), MBP (adjusted OR; 1.15, 95% CI, 1.03-1.29), PP
      (adjusted OR; 1.14; 95% CI, 1.02-1.26), MAP (adjusted OR; 1.15; 95% CI, 1.02
      1.31) and RPP (adjusted OR; 1.01; 95% CI, 1.00-1.02). Early recurrent stroke was
      associated with SBP, DBP, MBP and MAP. CONCLUSIONS: A poor outcome is
      independently associated with elevations in blood pressure, HR and their derived
      haemodynamic variables, including PP and the RPP. Agents that modify these
      measures may improve functional outcome after stroke.

PMID- 16794493
TI  - The renal antifibrotic effects of angiotensin-converting enzyme inhibition
      involve bradykinin B2 receptor activation in angiotensin II-dependent
      hypertension.
AB  - OBJECTIVE: The renoprotective action of angiotensin I-converting enzyme
      inhibitors (ACE-Is) is well established, but the role played by bradykinin (BK)
      remains unclear. We therefore investigated whether an enhanced BK effect on B2
      receptor subtype mediated the antifibrotic effect of ACE-Is and whether neutral
      endopeptidase (NEP) inhibition, which can blunt BK degradation more effectively
      than ACE inhibition, provided further renoprotection in a rat model of
      angiotensin (Ang) II-dependent renal damage. METHODS: Five-week-old Ren-2
      transgenic rats (TGRen2) received, for 8 weeks, a placebo, ramipril (5 mg/kg body
      weight) or the dual ACE + NEP inhibitor MDL 100,240 (MDL) (40 mg/kg body weight).
      After 4 weeks, the B2 receptor antagonist icatibant (0.5 mg/kg body weight) was
      administered on top of active treatment for 4 weeks to 50% of the TGRen2 rats.
      Blood pressure was measured weekly by a tail-cuff method and, after sacrifice,
      kidney weight, glomerular volume, density of glomerular profiles were measured;
      tubulo-interstitial fibrosis, glomerular and perivascular fibrosis were
      quantified by histomorphometry. RESULTS: The development of hypertension and
      tubulo-interstitial fibrosis was prevented by both ramipril and MDL (P = 0.0001
      versus placebo); icatibant annulled the latter effect. Glomerular and
      perivascular fibrosis were unaffected by either ramipril or MDL alone; however,
      combined treatment with icatibant enhanced glomerular fibrosis (P = 0.0001 versus
      placebo). CONCLUSION: Enhanced BK effect on B2 subtype receptors is essential for
      the prevention of tubulo-interstitial fibrosis with ACE or dual ACE + NEP
      inhibition in TGRen2 rats.

PMID- 16794494
TI  - The role of the RhoA/Rho-kinase signaling pathway in renal vascular reactivity in
      endothelial nitric oxide synthase null mice.
AB  - BACKGROUND: Smooth muscle contraction is regulated by the small GTPase RhoA and
      its target, Rho-kinase and recent evidence indicates that nitric oxide (NO)
      causes vasodilation through inhibition of the RhoA/Rho-kinase (ROCK) signaling
      pathway. AIM: This study tested the hypothesis that the enhanced renal vascular
      tone and systemic hypertension in endothelial nitric oxide synthase (eNOS) null
      mice is due to disinhibition of the ROCK signaling pathway. METHODS: Systolic
      blood pressure (SBP) was measured by tail-cuff plethysmography and the isolated
      Krebs-perfused kidney preparation was used to evaluate renal vascular responses
      in C57BL/6 (wild type, WT) and eNOS knockout (KO) mice treated with Y-27632, a
      ROCK inhibitor. RESULTS: Compared with the WT mice, Rho kinase activity was
      higher in eNOS KO mice (37 +/- 8%, P < 0.05) as was SBP (33 +/- 4%, P < 0.05),
      basal renal perfusion pressure (31 +/- 4%, P < 0.05) and renal vascular
      resistance (35 +/- 4%, P < 0.05). Y-27632 abolished these differences.
      Vasoconstriction elicited by angiotensin II (Ang II) or phenylephrine (PE), G
      protein-coupled receptor (GPCR) agonists, but not that elicited by arachidonic
      acid or KCl, was greater in eNOS KO mice. Y-27632 eliminated the amplified
      vasoconstriction elicited by Ang II or phenylephrine but to a greater extent in
      eNOS KO mice. Similarly, responses elicited by guanosine 5'-gamma
      thiotriphosphate (GTPgammaS), a non-hydrolyzable GTP analog, or sodium
      tetrafluoride (NaF4), an activator of G-proteins, was greater in eNOS KO mice, 53
      +/- 14 and 50 +/- 3%, respectively. Y-27632 normalized the difference. Y-27632
      also elicited a dose-dependent renal vasodilation that was greater in eNOS KO
      mice. CONCLUSIONS: These results show that the ROCK signaling pathway is
      amplified in the eNOS KO mouse kidney and that the enhanced renal vascular tone
      and selective increase in reactivity to GPCR agonists supports a role for ROCK in
      the hypertension and vascular dysfunction in the eNOS KO mice.

PMID- 16794495
TI  - Hydronephrosis causes salt-sensitive hypertension in rats.
AB  - BACKGROUND: Hypertension is a common disease in the Western world and
      approximately 5% of all cases are secondary to kidney malfunction. It is not
      clear whether unilateral hydronephrosis due to partial obstruction affects blood
      pressure. AIM: The aim of this study was to determine whether hypertension
      develops and to investigate the effects of different salt diets on the blood
      pressure in hydronephrotic animals. METHODS: Unilateral partial ureteral
      obstruction was created in 3-week-old Sprague-Dawley rats. A telemetric device
      was implanted 4-6 weeks later and blood pressure was measured on normal, low- and
      high-salt diets. Plasma samples were collected on all diets for renin analysis.
      RESULTS: All hydronephrotic animals developed hypertension that correlated to the
      degree of hydronephrosis. The blood pressure increased slowly with time and was
      salt sensitive. In severe hydronephrosis, blood pressure increased from 118 +/- 5
      mmHg on low salt to 140 +/- 6 mmHg on high salt intake, compared to control
      levels of 82 +/- 2 and 84 +/- 2 mmHg, respectively. Plasma renin concentration
      was increased in the hydronephrotic group of animals compared to controls on all
      diets, but the difference was only significant on a normal salt diet, 165 +/- 15
      versus 86 +/- 12 microGU/ml respectively. In animals with severe hydronephrosis
      the plasma renin levels were lower, and the changes less, than in those with mild
      and moderate hydronephrosis. CONCLUSION: This study demonstrates the presence of
      a salt-sensitive hypertension in hydronephrosis. A systemic effect of the renin
      angiotensin system alone cannot be responsible for the hypertension.

PMID- 16794496
TI  - Severe hypertension associated with the use of amphotericin B: an appraisal on
      the reported cases.

PMID- 16794497
TI  - Metronomic therapy from a pharmacologist's view.

PMID- 16794498
TI  - Commentary on TRALI in leukemia.
AB  - The paper by Fung YL and Williams BA describes TRALI in leukemic children in
      order to raise awareness of the need to include this in the differential
      diagnosis of acute respiratory distress. Detection of TRALI in children with
      other co-morbidities is difficult. Well-documented cases of TRALI in children are
      few due to the lack of recognition and difficulty in identifying the antibodies
      since these may not be always present. Hematology/oncology patients who are
      chronically transfused and are allo-immunized are at greater risk than the
      general pediatric population. Thus an awareness of this reaction to blood
      transfusion helps facilitate prompt treatment and preventive measures.

PMID- 16794499
TI  - Measurement of health-related quality of life in survivors of cancer in childhood
      in Central America: feasibility, reliability, and validity.
AB  - Cancer is the commonest cause of disease-related death in children over 5 years
      of age in various parts of Latin America, but the survival rates are improving.
      This study assessed the health status and health-related quality of life (HRQL)
      of more than 200 survivors of cancer in childhood in the countries of a Central
      American consortium devoted to pediatric hematology-oncology. Patients' self
      reports and parental proxy assessments were collected using interviewer
      administered Spanish-language questionnaires, and physicians provided assessments
      using self-complete questionnaires, based on the complementary Health Utilities
      Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems.
      Inter-rater agreement, measured by intra-class correlation (ICC), was fair to
      moderate (0.34<ICC<0.55) between patients, parents, and physicians for HRQL
      scores. There was substantial or almost perfect agreement (ICC>0.60) for all 3
      pairs of assessors for readily assessable attributes: HUI2 sensation, HUI3
      vision, HUI3 hearing, and HUI3 ambulation. Less than 40% of the patients reported
      being in perfect health. More than 20% reported being in health states with HRQL
      scores corresponding to moderate or severe disability, notably in the attributes
      of emotion and cognition. The results reflect a common profile in survivors of
      cancer in childhood, including those from industrialized societies. This study
      illustrates the feasibility of collecting reliable and valid information on HRQL
      in the developing country context, raising the prospect that such information
      could be used to influence clinical practice.

PMID- 16794500
TI  - Treatment of retinoblastoma patients with chemoreduction plus local therapy:
      experience of the AC Camargo Hospital, Brazil.
AB  - To evaluate the efficacy of conservative management of intraocular retinoblastoma
      with chemoreduction combined with local therapy with or without plaque radiation
      in the preservation of the eye, and avoidance of external beam radiation therapy
      (EBRT) (success rate). From 1995 to 2000, 84 newly diagnosed patients with
      intraocular retinoblastoma were admitted to the Pediatric Department of the
      Hospital do Cancer A.C. Camargo, Sao Paulo, Brazil. All children were treated
      with 2 to 6 cycles of chemotherapy (carboplatin, vincristine, and etoposide) plus
      local therapy (cryotherapy, laser photocoagulation, and thermotherapy), or plaque
      radiation therapy during and/or after the chemotherapy. The Mann-Whitney test was
      used to compare means of quantitative variables. The chi test or the Fisher exact
      test were employed to verify the association between the outcome and the
      independent variables. For all tests alpha=5% was adopted. Success rate was
      higher for patients with bilateral tumors (54%) than for children with unilateral
      tumors (19%) (P=0.003). For patients with Reese-Ellsworth stages I, II, and III,
      no statistically significant differences in the success rates were noted in the
      group of unilateral (50%) and bilateral tumors (79.1%) (P=0.179). Among children
      with Reese-Ellsworth stages IV and V, the success rate was significantly higher
      for patients with bilateral tumors (40.7%) than for those with unilateral (0%)
      (P=0.012). Chemoreduction combined with local therapy, with or without plaque
      radiotherapy, is efficacious in avoiding enucleation and the use of external beam
      radiation therapy for children with intraocular retinoblastoma.

PMID- 16794501
TI  - Celiac disease and childhood cancer.
AB  - Celiac disease is an autoimmune enteropathy developing in genetically predisposed
      individuals after mucosal contact with gluten, secondary to unknown triggering
      factors. An increased rate of malignancies in adults with celiac disease has been
      confirmed in several studies, but there is considerable evidence that a gluten
      free diet protects against the development of cancer. The association between
      celiac disease and childhood cancer is not clear. Few cases are reported in the
      literature. Here, we report the cases referred to our pediatric oncology unit
      with a review of the literature.

PMID- 16794502
TI  - Attitudes regarding fertility preservation in female adolescent cancer patients.
AB  - Infertility is a devastating side effect of cancer treatment. Advances in
      fertility research have brought new preservation techniques to the forefront for
      women. The implication of this research in the field of pediatric oncology has
      not been reported. The objective of this study was to determine whether female
      adolescents with a diagnosis of cancer and their parents were interested in
      trying to preserve fertility. We conducted a cross-sectional survey of female
      patients, aged 10 to 21 years, and their parents. There were 39 parent/adolescent
      pair responses, 3 parent-only responses, and 8 adolescent-only responses. We
      found that adolescents and parents had thought about the future and were
      interested in research treatments to help preserve fertility, but not willing to
      postpone cancer therapy. Achieving a state of good health was most important to
      the adolescent group (P<0.001). There was no statistical difference between
      attitudes of parents and adolescents. In summary, parents and female adolescents
      are interested in options to help preserve fertility during cancer treatments,
      but they are not willing to postpone treatment for this purpose.

PMID- 16794503
TI  - Reduced gene expression of clustered ribosomal proteins in Diamond-Blackfan
      anemia patients without RPS19 gene mutations.
AB  - Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell aplasia
      occasionally presenting physical anomalies. Ribosomal protein S19 gene (RPS19) is
      one of the causative genes for DBA; however, the pathologic mechanism of
      erythroblastopenia and abnormal morphology has not been clarified. To assess the
      pathophysiology of DBA, the gene expression profile of 2 representative patients
      carrying no RPS19 mutations was compared with that of aplastic anemia (AA)
      patients, assessed by the microarray analyses. The K-mean clustering analysis
      revealed the significant categorization of 28 ribosomal protein (RP) genes into a
      small set of group (994 genes) (P=2.39E-17), all of which were expressed at lower
      levels in DBA than in AA patients. RPS19 was categorized into the set of low
      expressing genes in DBA patients. No mutations were determined in the promoter
      and coding sequences of top 10 RP genes expressed at the levels over 1.2 of the
      AA/DBA ratio, in 3 DBA patients. These results indicated that the lower
      expression of RP gene group, even without the mutation, was a distinctive feature
      of DBA from AA, although the study number was small. The reduced RP gene
      expression, by itself, may suggest an underlying mechanism of the constitutional
      anemia.

PMID- 16794504
TI  - POG 8625: a randomized trial comparing chemotherapy with chemoradiotherapy for
      children and adolescents with Stages I, IIA, IIIA1 Hodgkin Disease: a report from
      the Children's Oncology Group.
AB  - To determine if 6 courses of chemotherapy alone could achieve the same or better
      outcome than 4 courses of chemotherapy followed by radiation therapy
      (chemoradiotherapy) in pediatric and adolescent patients with Hodgkin disease.
      Children < or =21 years old with biopsy-proven, pathologically staged I, IIA, or
      IIIA1 Hodgkin disease were randomly assigned 6 courses of alternating nitrogen
      mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin,
      vinblastine, and dacarbazine (treatment 1) or 4 courses of alternating nitrogen
      mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin,
      vinblastine, and dacarbazine +2550 cGy involved-field radiotherapy (treatment 2).
      The complete response rate was 89%, with a complete response and partial response
      rate of 99.4%. There was no statistically significant difference in event-free
      survival (EFS) or overall survival between arms. The EFS for those who achieved
      an early complete response was significantly higher than for those who did not.
      For pediatric patients with asymptomatic low-stage and intermediate-stage Hodgkin
      disease, chemotherapy and chemoradiotherapy both resulted in 3-year EFS of
      approximately 90% and statistically indistinguishable 8-year EFS and overall
      survival, without significant long-term toxicity. Early response to therapy was
      associated with higher EFS, a concept that has led to the Children's Oncology
      Group paradigm of response-based risk-adapted therapy for pediatric Hodgkin
      disease.

PMID- 16794505
TI  - An aggressive bone marrow evaluation including immunocytology with GD2 for
      advanced retinoblastoma.
AB  - There is general agreement that bone marrow (BM) examination for staging in
      patients with retinoblastoma should be limited to cases with advanced disease.
      However, there are limited data about the yield of sampling multiple sites with
      aspirations and biopsies and immunocytology. Our policy for BM examination
      included: 2 aspirates and 2 biopsies at the posterior iliac crest scheduled only
      for cases with postlaminar optic nerve extension (n=56), scleral invasion (n=10)
      or orbital (n=5) or metastatic disease at diagnosis (n=7) or at extraocular
      relapse (n=18). Immunocytology with the antibodies 3A7 or 3F8 for the ganglioside
      GD2 was performed. From 1/1994 to 3/2005, 277 newly diagnosed patients and 5 at
      extraocular relapse were included. BM invasion was not found in any of the 66
      patients enucleated with disease confined to the globe, but was found in 11/27 of
      those with overt extraocular disease. There were 2/11 cases with at least 1
      negative aspirate with positive biopsy and/or immunocytology for GD2. GD2
      positivity was found in 9/9 cases. A more aggressive BM evaluation has a low
      yield in enucleated patients with high-risk features but disease limited to the
      globe. However, in cases with overt extraocular dissemination, the use of BM
      biopsy and immunocytology for GD2 allowed for the detection of cases that would
      have been missed by aspirations alone. GD2 was intensively expressed and it may
      also be used to monitor disease response and the presence of minimal residual
      disease.

PMID- 16794506
TI  - Second neoplasms in pediatric patients treated for cancer: a center's 30-year
      experience.
AB  - To investigate the incidence and outcome of secondary neoplasms in pediatric
      patients treated for childhood cancer. Between December 1971 and January 2000, a
      total of 5859 patients younger than age 17 were diagnosed and treated for
      childhood cancers in our center. Of this group, 1511 (36%) patients were followed
      for more than 36 months. These long-term survivors were included in this
      analysis. Twenty-six patients developed a secondary malignancy with an overall
      risk of 1.7% in this cohort. The male:female ratio was 17:10, with a median age
      of 7.66 at diagnosis (range, 2 to 16 y). Four patients (14.8%) with Hodgkin
      lymphoma; 3 each (11.1%) with retinoblastoma and rhabdomyosarcoma; 2 each (7.4%)
      with Wilms tumor, Ewing sarcoma, medulloblastoma, ganglioneuroblastoma, and non
      Hodgkin lymphoma; and 1 each (3.7%) with ependymoma, nasopharyngeal carcinoma,
      osteosarcoma, astrocytoma had a secondary malignant disease during the long-term
      follow-up period. Secondary malignant diseases were osteosarcoma in 6 patients,
      acute lymphoblastic leukemia in 2, acute myelogenous leukemia in 2, and rare
      malignant disease in others. Four patients with osteosarcoma developed disease
      within the radiation field. Osteosarcoma was the most frequently occurring
      secondary neoplasm. Less toxic treatment modalities should be used to decrease
      the risk of secondary malignant diseases.

PMID- 16794507
TI  - Congenital neuroblastoma in a patient with partial trisomy of 2p.
AB  - We report the fourth example of a patient with germline partial trisomy of 2p21
      pter and congenital neuroblastoma. The male infant had a dysmorphic facial
      expression and presented with congenital heart disease, supernumerary nipples,
      hypospadias, shawl scrotum, hemilateral persistent hyperplastic primary vitreous,
      and neuroblastoma. His germline karyotype of 46,XY,der(8)t(2;8)(p21;p23.2) was
      inherited from a maternal-balanced translocation, which indicates that the proto
      oncogene MYCN region of 2p24.3 is tripicated in germline cells. A cytogenetic
      study of the biopsied tumor cells did not show MYCN amplification, but the DNA
      index was 2.4 and histologic fluorescent in situ hybridization analysis indicated
      somatic mutation with near-pentaploidy of the tumor cells. This could be an
      alternative mechanism of MYCN activation in the process of the tumorigenesis of
      neuroblastoma.

PMID- 16794508
TI  - Autologous peripheral blood stem cell transplantation in a patient with relapsed
      pleuropulmonary blastoma.
AB  - Pleuropulmonary blastoma (PPB) is a rare and aggressive primary intrathoracic
      neoplasma of children. The prognosis is extremely poor with frequent metastasis
      to the brain and bone. We present a 4-year-old girl with a tumor mass in the
      right hemithorax initially diagnosed as pneumoniae. Tumor resection was performed
      and the histologic report indicated the diagnosis of PPB. The patient received
      chemotherapy comprising vincristine, actinomycin D, doxorubicin, cisplatin, and
      cyclophosphamide. Irradiation was performed with total 45 Gy at the right lower
      pulmonary lobe. She relapsed 29 months later at the pleura between the right
      middle and lower pulmonary lobe. Tumor resection and total 45 Gy of irradiation
      were performed again. High-dose chemotherapy comprising cisplatin, adriamycin,
      and cyclophosphamide was performed followed by autologous peripheral blood stem
      cell transplantation (PBSCT). The patient achieved complete hematologic recovery.
      Thirty-one months after PBSCT, no signs of relapse have been observed. Although
      it might be that the patient could have been cured with second surgery alone or
      by the surgery and subsequent chemotherapy, high-dose chemotherapy and PBSCT
      should be considered for the treatment of relapsed PPB.

PMID- 16794509
TI  - Unresectable multifocal hepatoblastoma with cardiac extension: excellent response
      with HB-94 chemotherapy protocol.
AB  - A 10-month-old white infant presented with abdominal distention and bilateral
      scrotal hernia. Imaging studies of the abdomen and thorax showed a huge liver
      with multiple tumor masses and calcification involving all the segments. There
      was thrombosis in the inferior vena cava and right atrium. alpha-Fetoprotein was
      246,000 IU/mL. HB-94 chemotherapy protocol was started at once due to rapid
      deterioration of the patient. Surgical biopsy performed after the first IPA
      (ifosfamide, cisplatin, doxorubicin) course showed hepatoblastoma with
      macrotrabecular variant. After a second IPA course and 2 courses of carboplatin
      and etoposide, the boy's clinical condition was excellent with normal alpha
      fetoprotein but minimal regression and increased calcification in the tumor mass.
      Hepatic tumor was unresectable and no surgical intervention was performed.
      Transplantation could not be performed because of high morbidity and mortality.
      Despite general agreement that complete surgical resection is the cornerstone of
      treatment for patients with hepatoblastoma, the patient is in remission with 100%
      Karnofsky score in the 43 months of diagnosis.

PMID- 16794510
TI  - TRALI in 2 cases of leukemia.
AB  - We describe transfusion-related acute lung injury (TRALI) in 2 acute leukemia
      cases to increase awareness of this under reported serious transfusion
      complication syndrome in multitransfused patients. There are a number of reports
      in multitransfused patients with nonmalignant disorders. However, reports of
      pediatric oncology patients are few, suggesting a lack of recognition or
      misdiagnosis of the syndrome. A disproportionately high number of fatalities in
      children is recorded in the literature. This highlights the need for increased
      awareness and appropriate treatment of this serious complication of transfusion.
      Although TRALI is initially a clinical diagnosis, the laboratory investigation is
      vital as it contributes to defining the pathogenesis of the syndrome and
      importantly facilitates the effective management of implicated donations and
      donors. An investigational strategy for suspected cases is presented and the
      results are discussed in the context of current proposed mechanisms for TRALI. As
      each transfused blood product is associated with a potential risk of TRALI, more
      frequent reports in patients receiving large volume or recurrent transfusion
      would be expected.

PMID- 16794511
TI  - Methemoglobinemia associated with dapsone therapy in a child with pneumonia and
      chronic immune thrombocytopenic purpura.
AB  - This report describes a case of methemoglobinemia in association with dapsone
      therapy. The patient, an immunocompromised child with chronic immune
      thrombocytopenic purpura, presented with fever, cough, perioral cyanosis,
      bilateral lower lobe rales, and low O2 saturation by pulse oximetry (89%). His
      medications included prednisone and rituximab for chronic immune thrombocytopenic
      purpura, and dapsone for Pneumocystis carinii pneumonia prophylaxis. Because of
      his lack of dyspnea and tachypnea, and the temporal association of his perioral
      cyanosis with the initiation of dapsone therapy, a methemoglobin (MetHb) level
      was obtained and found to be elevated at 9.6%. The authors discuss the mechanism
      and treatment of methemoglobinemia secondary to dapsone. They also stress the
      importance of monitoring for signs and symptoms of methemoglobinemia in
      immunocompromised patients on dapsone therapy for P. carinii pneumonia
      prophylaxis.

PMID- 16794512
TI  - Combined local treatment and chemotherapy in the management of bilateral
      retinoblastomas in Hungary.
AB  - This retrospective study supports that brachytherapy combined with cytostatic
      therapy may effectively contribute to tumor control. The second eye of 13
      patients with bilateral retinoblastoma was treated with plaque brachytherapy
      after the enucleation of the first eye. Eleven patients received systemic
      cytostatic therapy. The mean follow up was 60 (+/-42 SD) months. Twelve patients
      are alive and free of tumor, 8 of them with acceptable visual acuity. After
      cytostatic therapy, late nephropathy was observed in 2 patients. In conclusion,
      brachytherapy combined with cytostatic therapy will be an option in the
      management of bilateral retinoblastoma after the enucleation of the first eye.

PMID- 16794513
TI  - Transfusion-related immune hemolytic anemia in thalassemic patients: report of 2
      cases.

PMID- 16794514
TI  - Molecular imaging of Takayasu's arteritis and other large-vessel vasculitis with
      18F-FDG PET.

PMID- 16794515
TI  - Improved quantification in 123I cardiac SPECT imaging with deconvolution of
      septal penetration.
AB  - OBJECTIVES: (123)I is becoming an important radionuclide for cardiac imaging.
      Multiple, low-abundance, high-energy photons associated with (123)I imaging can
      cause septal penetration in the collimators and degrade quantification of the
      (123)I cardiac uptake. This study presents a method for the deconvolution of
      septal penetration (DSP) for improving quantification in (123)I cardiac single
      photon emission computed tomography (SPECT). METHODS: Distance-dependent point
      spread functions were measured for low-energy high-resolution collimators on a
      dual-head SPECT system. The measured point spread functions were used in two
      dimensional (2-D) and three-dimensional (3-D) models of the collimator response,
      respectively. 2-D DSP and 3-D DSP were then developed and implemented using
      iterative reconstruction. A cardiac torso phantom with an internal calibration
      source was designed with various heart-to-calibration ratios (HCRs) simulating
      different levels of a patient's uptake. SPECT acquisitions of the phantom were
      performed using optimized acquisition and processing parameters for (123)I
      cardiac SPECT. HCRs were calculated using planar projection and tomographic
      reconstructions. The paired t-test and regression analysis were used to compare
      the HCRs given by different calculation methods. RESULTS: SPECT produced more
      accurate HCRs than planar imaging. The slopes of the regression lines for SPECT
      using filtered back-projection were statistically significantly higher than those
      for planar imaging (0.2118 +/- 0.0297 vs. 0.0819 +/- 0.0070, P = 0.0001). 2-D DSP
      and 3-D DSP yielded similar HCRs that were close to the true HCR. The slopes of
      the regression lines for 2-D DSP and 3-D DSP were 0.9203 +/- 0.0523 and 0.9101 +/
      0.0304, respectively. The DSP HCRs were significantly more accurate than those
      calculated without DSP (P < 0.0001). CONCLUSION: DSP significantly improves
      quantification in (123)I cardiac SPECT imaging. 2-D DSP with its less
      computational burden shows promise for implementation in clinical practice so as
      to allow the use of the widely available low-energy, high-resolution collimators
      for quantitative I cardiac SPECT imaging.

PMID- 16794516
TI  - Optimized radioiodine therapy for Graves' disease: two MIRD-based models for the
      computation of patient-specific therapeutic 131I activity.
AB  - AIM: (131)I therapy is increasingly used for Graves' hyperthyroidism. Debate
      remains about the best method for calculating the activity to administer, as well
      as about the potential benefit of such computed activity. Several arguments
      plead, nevertheless, in favour of a personalized computation, such as inter
      individual variations of thyroid volume and biokinetics. METHODS: A MIRD-based
      dosimetric approach, with an additional extension that takes into account the
      variation of thyroid mass during the treatment, has been developed. This approach
      includes the benefits of a personalized determination of biokinetics. Results
      were compared with those of six methods widely used in routine practice. Forty
      one patients were enrolled (34 women, seven men; mean age +/-SD: 48.11 +/- 6.4
      years). (131)I uptakes were measured at 4, 24 and 96 h (36.2 +/- 14.6%, 42.8 +/-
      9.7% and 27.6 +/- 6.8%, respectively), following administration of the tracer.
      The kinetics of iodine in the thyroid were evaluated using a two-compartment
      model (effective half-life of 5.1 +/- 1.6 days). Computations of activities to
      deliver the doses prescribed by the physician were done with the eight
      formalisms. RESULTS: There was no statistical difference between results of the
      two MIRD-based formalisms (227 +/- 148 MBq and 213 +/- 124 MBq), which were also
      not significantly different from those obtained with the majority of the other
      methods (from 128 +/- 95 MBq to 275 +/- 223 MBq). However, a large intra
      individual difference up to a factor of 2 between two given methods was found.
      CONCLUSION: The formalism developed appears to be a good compromise between all
      the common formalisms already used in many institutions. Furthermore, it allows
      the exposures of target volumes and non-target volumes to be planned individually
      and practical individual radiation protection recommendations to be implemented.

PMID- 16794517
TI  - Efficacy of radioiodine therapy in the treatment of elevated serum thyroglobulin
      in patients with differentiated thyroid carcinoma and negative whole-body iodine
      scan.
AB  - INTRODUCTION: In the management of patients with differentiated thyroid
      carcinoma, serum thyroglobulin levels are often well correlated with whole-body
      radioiodine scanning (WBS) results. However, occasionally, a mismatched result -
      increased thyroglobulin with negative WBS - is observed. Radioiodine therapy has
      been suggested as a therapeutic choice with controversial results. METHOD: We
      studied 32 differentiated thyroid carcinoma patients with elevated thyroglobulin
      level and negative WBS who had been treated with high-dose radioiodine. With a
      mean follow-up of 25.6 months (all follow-ups >11 months), thyroglobulin and
      thyroid-stimulating hormone levels, WBS, clinical, radiographic and pathological
      findings following treatment were recorded. RESULTS: The mean pre-therapy off
      treatment thyroglobulin was 152 +/- 119.0 ng.ml(-1). Although there was a mild
      trend towards an increase in thyroglobulin in the first post-treatment year, the
      difference was not significant. At the end of the follow-ups, 22 patients (68.7%)
      were categorized as non-responders to radioiodine therapy (any change or
      elevation of thyroglobulin or radiological and pathological evidences of
      progression), four patients (12.5%) as partial responders (transient reduction
      but not a normalization of thyroglobulin) and six patients (18.7%) as responders
      (normalization of thyroglobulin with no evidence of remnant disease). In nine of
      10 partial and complete responders, reduction or normalization of thyroglobulin
      had occurred in the first post-treatment year. CONCLUSION: We recommend that in
      differentiated thyroid carcinoma patients with elevated thyroglobulin and
      negative WBS, at least one course of radioiodine therapy should be undertaken and
      if reduction or normalization of serum thyroglobulin is not achieved, repeated
      courses of radioiodine therapy are not logical and other therapeutic methods
      should be applied.

PMID- 16794518
TI  - Quantitative measurement of oxygen metabolic rate in the rat brain using microPET
      imaging of briefly inhaled 15O-labelled oxygen gas.
AB  - OBJECTIVE: The quantitative measurement of cerebral metabolic rate of oxygen
      (CMRO(2)) for rats using positron emission tomography (PET) has been technically
      difficult. The present study was performed to provide a technique to measure
      CMRO(2) for rats using a dedicated animal PET technique. METHODS: CMRO(2) in the
      rat brain was quantitatively measured under alpha-chloralose anaesthesia (30 mg .
      kg(-1) . h(-1), intravenous infusion) using a PET imaging technique. In our
      experiment, the (15)O-labelled gas tracer (O(15)O) was administered by a bolus
      insufflation into the lung through a surgically placed cannula in the trachea.
      The tracer distribution was then dynamically imaged using the microPET. Unlike
      other conventional PET methods in which a series of arterial blood samples need
      to be withdrawn for the measurement of an arterial input function, no arterial
      blood sampling was employed. Instead, the heart was scanned in dynamic mode at
      the same time of imaging the brain, and the region of interest drawn over the
      heart was analysed to obtain an arterial input function. RESULTS: The CMRO(2)
      value (micromol . 100 g(-1) . min(-1)) from 10 rats was 208 +/- 15 (mean +/- SD).
      CONCLUSIONS: Our results suggest that the microPET-based CMRO(2) measurement in
      the rat brain combined with a non-invasive measurement of arterial input function
      is promising, especially for many applications involving small animals in which
      repeated measurements of absolute CMRO(2) need to be performed.

PMID- 16794519
TI  - Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy
      in localizing pheochromocytomas: a prospective study.
AB  - AIM: To establish a standardized non-invasive imaging protocol for patients with
      pheochromocytoma undergoing surgery. METHODS: A series of 32 consecutive patients
      (16 men, 16 women; median age 43 years, range 15-71 years) with biochemically
      confirmed pheochromocytoma underwent computed tomography (CT) scanning, magnetic
      resonance imaging (MRI) and meta-[I]iodobenzylguanidine (MIBG) whole-body
      scintigraphy prior to adrenalectomy or excision of extra-adrenal tumour
      (paraganglioma). RESULTS: At final pathology no malignant pheochromocytomas were
      found. The tumour was right-sided in 16 (50%) patients, left-sided in 13 (41%),
      extra-adrenal (sympathetic ganglia, upper abdomen) in two (6%) and bilateral in
      one (3%) patient. Overall, the median greatest diameter (size) of the tumour was
      35 mm (range, 15-90 mm). The sensitivity of CT, MRI and MIBG scintigraphy was
      90%, 93% and 91%, and the specificity was 93%, 93% and 100%, respectively. The
      three patients with false negative scintigraphy had an intra-adrenal tumour,
      ranging from 20 to 50 mm in size. The presence of necrosis within the mass might
      justify the lack of significant uptake of radiopharmaceutical in two patients,
      and the small size (15 mm) of the mass in the other. There were two false
      positive results with both CT and MRI, and no false positive MIBG scintigraphy,
      which had the highest (100%) positive predictive value. The combination of
      MRI+MIBG scintigraphy reached 100% sensitivity and positive predictive value.
      CONCLUSION: Our data suggest that this imaging protocol should be used in all
      patients with biochemically confirmed pheochromocytoma.

PMID- 16794520
TI  - A meta-analysis of scintimammography: an evidence-based approach to its clinical
      utility.
AB  - BACKGROUND: Scintimammography using (99m)Tc-labelled isonitriles, sestamibi and
      tetrofosmin, has become a mature technique in the adjunctive setting for the
      diagnosis of primary breast cancer. To establish an evidence base for its use,
      clinically, a meta-analysis was performed on both single-site and multi-centre
      trials performed since January 1997. METHODS: Using an on-line literature search
      all such trials containing 100 or more studies were identified. To prevent double
      counting of patients only the last published report from any centre was used.
      RESULTS: A total of 2424 patients were identified in the single-site trial group,
      the smallest study having 105 patients and the largest 353 patients. The overall
      sensitivity was 85% and the specificity was 84%. In the multi-centre trial
      studies, published data from 3049 patients were included. The overall sensitivity
      in this group was also 85% and the specificity was 83%. CONCLUSION: There is
      evidence that this is a robust imaging technique delivering high sensitivities
      and specificities in patients studied in both single-centre and multi-centre
      trials and, as such, can be relied on as an adjunctive method for the
      investigation of primary breast cancer.

PMID- 16794521
TI  - 90Y-Ibritumomab tiuxetan: new drug, interesting concept, and encouraging in
      practice.

PMID- 16794523
TI  - Lung transplantation: current status and challenges.
AB  - The lung is an anatomically complex vital organ whose normal physiology depends
      on actively regulated ventilation and perfusion, and maintenance of a delicate
      blood-air barrier over a huge surface area in direct contact with a potentially
      hostile environment. Despite significant progress over the past 25 years, both
      short- and long-term outcomes remain significantly inferior for lung recipients
      relative to other "solid" organs. This review summarizes the current status of
      lung transplantation so as to frame the principle challenges currently facing end
      stage lung-failure patients and the practitioners who care for them.

PMID- 16794524
TI  - Hematopoietic stem cell transplant research with pediatric donors: when can
      institutional review boards approve it?
AB  - Although pediatric donation of hematopoietic stem cells (HSCs) for allogeneic
      transplants is common in the clinical setting, the question of when children may
      donate HSCs in research has received little attention. Our analysis reveals that
      institutional review boards (IRBs) may approve children's participation as HSC
      donors in transplant research when it poses no more than minimal risk to them.
      The risks that IRBs should consider are those that result specifically from the
      research, as opposed to risks donors would have faced regardless of the research.
      Transplant protocols that expose pediatric donors to more than minimal risk can
      be approved by the Secretary of U.S. Department of Health and Human Services in a
      special category of pediatric research.

PMID- 16794525
TI  - Avascular bone necrosis of the hip joint after solid organ transplantation in
      childhood: a clinical and MRI analysis.
AB  - BACKGROUND: Aseptic osteonecrosis is a well-known complication after solid organ
      transplantation in adults. The occurrence of osteonecrosis in growing age has
      been studied after kidney transplantation, but no systematic evaluation of the
      joints has been reported after heart or liver transplantation in childhood.
      METHODS: A total of 196 children--93% of patients surviving kidney, liver and
      heart transplantation in Finland--participated in a cross-sectional survey. All
      children underwent a detailed clinical examination and filled out a questionnaire
      on musculoskeletal symptoms. Radiographs were taken in case of joint pain or
      abnormal clinical findings. In addition, magnetic resonance imaging (MRI) from
      the hips was taken on a random basis from 34 adult patients transplanted as a
      child. The mean follow-up time of all patients after transplantation was 9.2
      years (range, 2.4 to 20.5 years). RESULTS: Twenty-eight (14%) patients reported
      prolonged joint or limb pain without previous trauma. Specific etiology for the
      limb pain was not found in 10 (5.1%) patients. Osteonecrosis seen in radiographs
      or MRI was noted in seven (3.6%) patients, of which three had received kidney,
      three liver, and one heart graft. Femoral head was affected in five patients, as
      well as talus bilaterally in one patient and lateral femoral condyle in one
      patient. All patients were older than 12 years at the time of diagnosis of the
      osteonecrosis. MRI of the hips of 34 randomly selected patients showed only one
      asymptomatic necrosis of the femoral head. CONCLUSIONS: Symptomatic osteonecrosis
      of the hip is uncommon after solid organ transplantation in childhood using the
      current immunosuppressive medications.

PMID- 16794526
TI  - Thrombotic microangiopathy with acquired deficiency in ADAMTS 13 activity in lung
      transplant recipients.
AB  - BACKGROUND: Thrombotic microangiopathy may develop after solid organ
      transplantation, but it is usually not associated with severe deficiency in von
      Willebrand factor-cleaving metalloprotease (ADAMTS 13) activity. METHODS: We
      present the cases of two lung transplant recipients who experienced a thrombotic
      microangiopathy associated with an acquired severe (<5%) deficiency in ADAMTS 13
      activity. RESULTS: A major feature of both cases was the occurrence of a diffuse
      alveolar hemorrhage. CONCLUSION: Our two cases of lung transplant patients, with
      thrombotic microangiopathy related to an acquired ADAMTS 13 deficiency
      recipients, confirm that this mechanism may also be involved in the pathogenesis
      of thrombotic microangiopathy developing after solid organ transplantation.
      Therefore, we consider that ADAMTS 13 activity should be assessed on a systematic
      basis in this setting.

PMID- 16794527
TI  - Accuracy of staging as a predictor for recurrence after liver transplantation for
      hepatocellular carcinoma.
AB  - BACKGROUND: Tumor number, size, and macrovascular invasion (MacroVI) are the most
      widely used predictors of survival after liver transplantation (LT) for
      hepatocellular carcinoma (HCC). We analyzed all patients undergoing LT for HCC at
      our center to establish the accuracy of preoperative clinical staging and to
      determine which patients have a higher probability of being understaged. METHODS:
      In all, 118 patients with confirmed HCC after LT from April 1991 to October 2004
      at our institution were reviewed. All patients were monitored with serial imaging
      every 3 months to ensure their eligibility for LT within Milan criteria.
      Understaging in the 118 patients was defined as evidence on explant pathology
      that Milan criteria (TNM stage pT1 or pT2) had been exceeded. RESULTS: Five-year
      DFS was 78% with a recurrence rate of 15% after a median follow-up after LT of 30
      months. On explant pathology, 43% (51/118) of patients exceeded Milan criteria
      and had a worse DFS (1 year, 95% vs. 87%; 3 year, 87% vs. 64%; P=0.03) compared
      to those who met LT criteria. Understaging was more likely in patients with
      imaging characteristics of > or = 2 tumor nodules (P=0.005) and tumor growth >
      0.25 cm/month (P=0.02) and pathologic findings of vascular invasion (P=0.001) and
      bilobar tumors (P=0.002). CONCLUSIONS: Preoperative imaging every 3 months while
      on the waiting list frequently understages HCC as assessed by explant pathology.
      Recurrence after LT often occurred in patients that were understaged. Improving
      the accuracy of clinical staging and inclusion parameters will ensure proper
      organ allocation and acceptable outcomes after LT.

PMID- 16794528
TI  - Quality of life in adult transplant recipients more than 15 years after kidney
      transplantation.
AB  - BACKGROUND: With continuously rising survival rates following renal
      transplantation, health-related quality of life (HQOL) of long-term transplant
      survivors becomes increasingly important. METHODS: Recipients more than 15 years
      after successful renal transplantation were studied retrospectively. HQOL in 139
      long-term transplant recipients was assessed using the SF-36 and the disease
      specific kidney transplant questionnaire (KTQ-25). RESULTS: Long-term transplant
      recipients revealed satisfactory HQOL that was comparable to the healthy
      population in four of eight SF-36 categories (role physical, social functioning,
      role emotional and mental health). Other SF-36 categories such as physical
      functioning, physical pain, general health, and vitality were reduced. Among the
      study population, disease-specific HQOL was comparable or even improved to that
      of patients awaiting transplantation. In contrast to retired or unemployed
      patients, employed recipients revealed a highly significant improved HQOL in
      numerous SF-36 categories such as physical functioning (P<0.001), physical pain
      (P<0.001), general health (P<0.001), vitality (P<0.001), social functioning
      (P<0.005), and mental health (P<0.001), as well as for the KTQ-dimensions
      physical symptoms (P<0.001), fatigue (P>0.001), uncertainty/fear (P<0.01), and
      emotions (P<0.05). Other factors positively correlating with improved HQOL in
      certain dimensions were living situation, systolic blood pressure, and recipient
      age. CONCLUSIONS: More than 15 years after renal transplantation, recipients
      present satisfactory HQOL comparable to the general healthy population or at
      least to pretransplant patients. Vocational rehabilitation following renal
      transplantation is of highest importance among long-term survivors and is
      associated with improved HQOL.

PMID- 16794529
TI  - Impact of cytomegalovirus in organ transplant recipients in the era of antiviral
      prophylaxis.
AB  - BACKGROUND: Antiviral prophylaxis has been shown to decrease the incidence of
      cytomegalovirus (CMV) disease in organ transplant recipients, but whether CMV
      disease that occurs despite prophylaxis is associated with mortality remains
      unknown. METHODS: The clinical features and risk factors for CMV disease in a
      cohort of liver transplant recipients who received antiviral prophylaxis were
      assessed retrospectively. Cox proportional hazard regression was used to assess
      the relationship of CMV to mortality during the first posttransplant year.
      RESULTS: CMV disease developed in 37 of 437 (8.5%) recipients at a median of 4.5
      (range, 2.5 to 12) months posttransplant and was associated only with donor
      seropositive/recipient-seronegative serostatus in multivariate analysis
      (P<0.0001). Mortality at 1 year was 12% (51 of 437) and was infection-associated
      in 49% of cases. In multivariate analysis, CMV disease was independently
      associated with overall mortality at 1 year (HR, 5.1, P=0.002) and even more
      strongly with infection-associated mortality (HR 11, P=0.002). There was no
      association of CMV with noninfection-associated mortality (P>0.05). CONCLUSIONS:
      Late CMV disease is an important clinical problem in liver transplant recipients
      who receive antiviral prophylaxis, and is strongly and independently associated
      with mortality. Strategies to prevent late CMV disease are warranted.

PMID- 16794530
TI  - Urine cytokines profile in renal transplant patients with asymptomatic
      bacteriuria.
AB  - BACKGROUND: The role of asymptomatic bacteriuria in kidney transplant recipients
      is unknown. There is no clear evidence of its effect on transplanted kidney.
      METHODS: We studied urine cytokines profile among kidney transplant recipients
      with bacteriuria found in screening examination. Urine cultures were collected in
      269 patients with stable graft function and serum creatinine level <2 mg/dl,
      during their routine visits. Interleukin (IL)-6 and IL-8 levels were measured in
      urine samples from patients with asymptomatic bacteriuria, symptomatic urinary
      tract infection and patients without bacteriuria (control group). Changes in
      serum creatinine level in patients with asymptomatic bacteriuria and in the
      control group were observed during 12 months follow up. RESULTS: Urinary tract
      infection (UTI) was diagnosed in five patients and asymptomatic bacteriuria in 22
      patients. Urine IL-6 level was significantly higher in symptomatic UTI group
      (median 15.71 pg/mg) but there were no differences between group of patients with
      asymptomatic bacteriuria (3.92 pg/mg) and control group (2.54 pg/mg). Urine IL-8
      level was higher in symptomatic UTI group (median 146.8 pg/mg) and was also
      significantly higher in asymptomatic bacteriuria group (33.49 pg/mg) in
      comparison to control group (2.97 pg/mg; P=0.0002). During 1-year follow up,
      incidence of UTI was higher in the asymptomatic bacteriuria group than in the
      control group but graft function was not different in both groups. CONCLUSIONS:
      Elevated urine IL-8 level in kidney transplant patients with asymptomatic
      bacteriuria may reflect impaired immune response to bacterial infection and
      occult inflammatory process in urinary tract.

PMID- 16794531
TI  - HIV-positive renal recipients can achieve survival rates similar to those of HIV
      negative patients.
AB  - BACKGROUND: Although patients positive for HIV were once thought to be unsuitable
      candidates for kidney transplantation, their increasing numbers with end-stage
      renal disease (ESRD) and the introduction of highly active antiretroviral therapy
      has indicated that they should no longer be excluded for transplantation. To
      counteract suggestions that human immunodeficiency virus (HIV) patients received
      suboptimal kidneys, we provide studies of kidneys transplanted from the same
      donor into patients with and without HIV. METHODS: United Network for Organ
      Sharing kidney transplant data between 1997 and 2004 were analyzed. Graft and
      patient survival of 38 HIV patients who had received a renal transplant were
      compared with the survival of 38 recipients who had received a graft from the
      same donor. RESULTS: The 38 HIV-positive recipients were younger (49.0 vs. 52.3
      years, P=0.14) and had lower peak panel-reactive antibodies (PRA; 5.1% vs. 15.6%,
      P=0.07) when compared with their bilateral donor to HIV-negative recipients.
      Sirolimus was used more frequently in HIV patients than in non-HIV patients
      (36.8% vs. 23.7%, P=0.09). The serum creatinine at 1, 3, and 5 years
      posttransplantation were higher in HIV patients when compared to non-HIV
      patients. Although not statistically significant, graft survival was higher among
      HIV-positive patients compared with their negative controls (76.1% vs. 65.1% at 5
      years, P=0.21), as was patient survival (91.3% vs. 87.3% at 5 years, P=0.72).
      More grafts failed due to death with a functioning graft than rejection in HIV
      positive patients. CONCLUSION: This study supports the position that there is no
      longer an ethical question surrounding the use of kidneys for HIV-positive
      patients.

PMID- 16794532
TI  - Infection frequency and profile in different age groups of kidney transplant
      recipients.
AB  - BACKGROUND: Older transplant recipients have been shown to be at greater risk for
      infectious death than younger adults, but no study to date has looked at relative
      risk of infection and infection profile differences for children versus adults,
      which may be very different from one another. METHODS: Data from primary Medicare
      renal transplant recipients between 1991 and 1998 (n=64,751), as reported in the
      United States Renal Data System (USRDS), were analyzed for Medicare claims (both
      inpatient and outpatient) for infection and type of infection in the first year
      posttransplant. Cox regression was used to model adjusted hazard ratios (AHR) for
      infection. RESULTS: Total infections among renal transplant recipients increased
      significantly in more recent years. Patients transplanted in or after 1995 had a
      significantly higher adjusted risk for infection compared to those transplanted
      earlier (AHR 1.34, 95% CI=1.29-1.39). Older adults > or = 51 years of age had the
      highest percentage of experiencing infection, as compared to adults between 18-50
      years and children < or = 17 years (P<0.001). Children were at highest risk of
      viral infection prior to 1995 but at lowest risk of viral infection after 1995,
      whereas elderly adults were at highest risk of bacterial infection throughout the
      study. Children experienced more claims for viral infections, whereas older
      transplant recipients experienced more claims for bacterial infections.
      CONCLUSIONS: The two extremes of transplant recipient age display very different
      risks for infection claim frequency and profile.

PMID- 16794533
TI  - Preparation of cultured skin for transplantation using insulin-like growth factor
      I in conjunction with insulin-like growth factor binding protein 5, epidermal
      growth factor, and vitronectin.
AB  - BACKGROUND: Cultured skin for transplantation is routinely prepared by growing
      patient keratinocytes in the presence of semidefined sources of growth factors
      including serum and feeder cells, but these materials require substantial risk
      remediation and can contribute to transplant rejection. METHODS: We have
      therefore investigated the potential of a novel combination of recombinant and
      purified growth factors to replace serum and feeder cells in cultures of human
      keratinocytes suitable for clinical application. Our technique was investigated
      with respect to culture establishment, serial propagation, colony-forming
      efficiency, immunocytochemistry, epidermal reconstruction, and suitability to
      support transplantation by aerosolization. RESULTS: We demonstrate that insulin
      like growth factor (IGF)-I--used in conjunction with epidermal growth factor
      (EGF), insulin-like growth factor binding protein (IGFBP)-5 and vitronectin-
      supports growth in the absence of serum. Moreover, a threefold greater number of
      cells are generated within 7 days compared to those grown under current best
      practice conditions using serum (P<0.05). The resulting test cultures are
      suitable for epidermal reconstruction and support the option for delivery in the
      form of an aerosolized cell suspension. Serial propagation, with the view to
      producing confluent sheets for extensive injuries, was achieved but with less
      consistency and this result correlated with a significant decline in colony
      forming efficiency compared to controls. CONCLUSIONS: IGF-I used in conjunction
      with IGFBP-5, EGF, and vitronectin provides a superior alternative to serum for
      the rapid expansion and transplantation of cultured keratinocytes within the
      first week of treatment. Nevertheless, further optimization is required with
      respect to elimination of feeder cells and serial expansion of cultures for
      treatment of extensive injuries.

PMID- 16794534
TI  - Stable multilineage chimerism without graft versus host disease following
      nonmyeloablative haploidentical hematopoietic cell transplantation.
AB  - BACKGROUND: Hematopoietic cell transplantation may offer the only cure for
      patients with hematological diseases. The clinical application of this therapy
      has been limited by toxic conditioning and lack of matched donors. Haploidentical
      transplantation would serve to extend the potential donor pool; however,
      transplantation across major histocompatibility complex barriers is often
      associated with severe graft-versus-host disease. Here we evaluate a novel
      protocol to achieve engraftment across mismatch barriers without toxic
      conditioning or significant posttransplant complications. METHODS: Nine major
      histocompatibility complex (MHC)-defined miniature swine received haploidentical
      hematopoietic cell transplantation following standard myeloablative conditioning.
      Nine additional animals received haploidentical hematopoietic cell
      transplantation following a minimally myelosuppressive regimen, consisting of 100
      cGy total body irradiation, immunotoxin mediated T-cell depletion, and a short
      course of cyclosporine. Donor cell engraftment and peripheral chimerism was
      assessed by polymerase chain reaction and flow cytometry. Graft-versus-host
      disease was monitored by clinical grading and histology of skin biopsy specimens.
      RESULTS: All animals conditioned for haploidentical hematopoietic cell
      transplantation using myeloablative conditioning were euthanized within 2 weeks
      due to engraftment failure or graft-versus-host disease. All animals conditioned
      with the nonmyeloablative regimen developed multilineage peripheral blood
      chimerism during the first 2 months following transplantation. Six animals
      evaluated beyond 100 days maintained multilineage chimerism in the peripheral
      blood and lymphoid tissues, showed evidence of progenitor cell engraftment in the
      bone marrow, and had minimal treatment-related complications. CONCLUSIONS: Here
      we report that stable multilineage chimerism and engraftment can be established
      across haploidentical major histocompatibility complex barriers with minimal
      treatment-related toxicity and without significant risk of graft-versus-host
      disease.

PMID- 16794535
TI  - Effect of an anti-C5a monoclonal antibody indicates a prominent role for
      anaphylatoxin in pulmonary xenograft dysfunction.
AB  - BACKGROUND: In contrast to renal or cardiac xenografts, the inhibition of
      complement using cobra venom factor (CVF) accelerates pulmonary xenograft
      failure. By activating C3/C5 convertase, CVF depletes complement while
      additionally generating C5a and other anaphylatoxins, to which pulmonary
      xenografts may be uniquely susceptible. The current study investigates the role
      of C5a in pulmonary xenograft failure in baboons. METHODS: Left orthotopic
      pulmonary xenografts using swine lungs expressing human CD46 were performed in
      baboons receiving: I) no other treatment (n=4), II) immunodepletion (n=5), and
      III) immunodepletion plus a single dose of mouse anti-human C5a monoclonal
      antibody (anti-C5a, 0.6 mg/kg administered intravenously) (n=3). The extent to
      which anti-C5a inhibits baboon C5a was assessed in vitro using a hemolytic
      reaction involving baboon serum and porcine red blood cells and by ELISA.
      RESULTS: Baboons in Group III exhibited significantly prolonged xenograft
      survival (mean=722+/-121 min, P=0.02) compared to baboons in Group I (mean=202+/
      24 min) and Group II (mean=276+/-79 min). Furthermore, baboons in Groups I and II
      experienced pronounced hemodynamic compromise requiring inotropic support whereas
      those in Group III remained hemodynamically stable throughout experimentation
      without the need for additional pharmacologic intervention. CONCLUSIONS: These
      findings indicate that C5a exacerbates pulmonary xenograft injury and compromises
      recipient hemodynamic status. Moreover, blockade of anaphylatoxins, such as C5a,
      offers a promising approach for future investigations aimed at preventing
      pulmonary xenograft injury in baboons.

PMID- 16794536
TI  - Influence of stem cell mobilization and liver regeneration on hepatic parenchymal
      chimerism in the rat.
AB  - BACKGROUND: Despite the newly discovered plasticity of hematopoietic stem cells,
      their capacity to "transdifferentiate" into parenchymal cells and the regulation
      of this process is not yet elucidated. The present study was designed to
      investigate the effect of stem cell mobilization and liver regeneration on this
      process using a syngeneic rat female-to-male liver transplantation model.
      METHODS: Rate and frequency of Y-chromosome containing hepatocytes was determined
      by fluorescence-in situ hybridization (FISH) using a rat Y-chromosome specific
      probe. Rats were subjected to full-size or partial liver transplantation with and
      without stem cell mobilization using granulocyte colony stimulating factor (G
      CSF). The effect of stem cell mobilization was confirmed by assessing the white
      blood count and by evaluating the migration of granulopoietic precursor cells to
      the liver. RESULTS: Treatment with G-CSF induced a twofold increase of peripheral
      white blood cells and a strong influx of granulopoietic precursor cells into the
      liver. Transplantation of a partial liver graft was followed by a 90% recovery of
      the original liver weight within a week, demonstrating the strong regenerative
      stimulus. Irrespective of the experimental model, the incidence and rate of Y
      chromosome containing hepatocytes never exceeded 0.77%. CONCLUSION: Neither stem
      cell mobilization nor liver regeneration enhanced the incidence or rate of stem
      cell derived hepatocytes in a liver graft with unimpaired regenerative potential.

PMID- 16794537
TI  - Cytosolic phospholipase A2 inhibition attenuates ischemia-reperfusion injury in
      an isolated rat lung model.
AB  - BACKGROUND: Arachidonic acid metabolites and platelet-activating factor (PAF) are
      potentially involved in ischemia-reperfusion (IR) lung injury. A key enzyme
      regulating their metabolism is cytosolic phospholipase A2 (cPLA2). Arachidonyl
      trifluoromethyl ketone (AACOCF3) is reported to be a potent cPLA2 inhibitor. In
      the present study, we hypothesized that pharmacological inhibition of cPLA2 might
      ameliorate IR lung injury. METHODS: To test the hypothesis, we examined the
      effects of AACOCF3 in an isolated rat lung model. Three groups were defined (n=6,
      each): in the vehicle group, lungs were perfused for 2 hours without an ischemic
      period. In the ischemic groups, 20 mg/kg of AACOCF3 (AACOCF3 group) or saline
      (control group) was i.v. administered 15 min before lung harvest. Lungs were
      flushed with LPD solution, cold-stored 18 hours, and reperfused for 2 hours.
      RESULTS: IR increased cPLA2 activity mainly via alveolar macrophages, sPLA2
      activity, thromboxane and leukotriene formation, and the expression of PAF
      receptor, whereas AACOCF3 treatment significantly reduced all of these. Compared
      to the vehicle group, the wet-to-dry ratio, proteins in BAL, and MPO activity
      increased significantly by twofold, fourfold, and threefold, respectively.
      Furthermore, the PO2 dropped from 615.7+/-31.2 to 452.1+/-30.9 mmHg at the end of
      reperfusion (P<0.001). AACOCF3 treatment maintained the PO2 at a level similar to
      the vehicle group throughout reperfusion and reduced significantly the alveolar
      capillary leakage, edema formation, and neutrophil extravasation. CONCLUSION:
      Pharmacological inhibition of the cPLA2 cascade decreases bioactive lipid
      formation and attenuates IR-induced lung injury.

PMID- 16794538
TI  - Production of nitric oxide during graft rejection is regulated by the Th1/Th2
      balance, the arginase activity, and L-arginine metabolism.
AB  - BACKGROUND: Production of nitric oxide (NO) by graft infiltrating macrophages has
      been proposed as an important effector mechanism of allograft rejection. Although
      high levels of NO are generated during allograft rejection, undetectable or only
      limited amounts of NO were found in rejected skin xenografts. METHODS: BALB/c
      mice were grafted with skin transplants from syngeneic, allogeneic or xenogeneic
      (rat) donors. The production of NO, cytokines and arginase in the grafts was
      determined by spectrophotometry, enzyme-linked immunosorbent assay, or polymerase
      chain reaction. Effects of depletion of CD4+ cells, neutralization of interleukin
      (IL)-4 or application of arginase inhibitors N(omega)-hydroxy-L-arginine (L-NOHA)
      and L-valine on production of NO in rejected xenografts were evaluated. RESULTS:
      Rejection of rat skin xenografts, on the contrary to rejection of allografts, was
      associated with a local high production of Th2 cytokines IL-4 and IL-10,
      overexpression of arginase genes, strongly enhanced arginase activity and
      attenuated NO generation in the graft. The supernatants obtained after
      cultivation of skin xenograft (but not allograft or syngeneic graft) explants
      contained a high arginase activity and strongly suppressed NO production by
      activated macrophages. This suppression was completely inhibited by L-NOHA or was
      overcome by an excess of exogenous L-arginine, a substrate for NO synthesis.
      Cocultivation of xenograft explants that did not produce NO with arginase
      inhibitors L-NOHA or L-valine restored NO generation in the graft. CONCLUSION:
      The results suggest that upregulation of arginase activity by Th2 cytokines
      during xenograft rejection limits the bioavailability of L-arginine for the
      inducible NO synthase and thus attenuates generation of NO by the graft
      infiltrating macrophages.

PMID- 16794539
TI  - Association of high pretransplant sIL-6R plasma levels with acute tubular
      necrosis in kidney graft recipients.
AB  - BACKGROUND: Delayed graft function is primarily caused by acute tubular necrosis
      (ATN). We studied in renal transplant recipients with posttransplant graft biopsy
      whether an up-regulated immune system in the recipient immediately before
      transplantation affects the risk of developing ATN and might be relevant for the
      pathogenesis of ATN. METHODS: In a retrospective study, we analyzed pretransplant
      and early posttransplant soluble interleukin (sIL)-1RA, interleukin (IL)-2, sIL
      2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor (TNF)-alpha,
      transforming growth factor (TGF)-beta2, interferon (IFN)-gamma, and neopterin
      plasma levels in patients with ATN (n=26). Matched patients with acute rejection
      (AR) (n=26) or normal posttransplant biopsy (n=26) served as controls. RESULTS:
      Pretransplant sIL-6R was higher (P=0.0004) and pretransplant TGF-beta2 lower
      (P=0.002) in patients with ATN than in patients with normal biopsy. ROC curves
      showed that high pretransplant sIL-6R has a high sensitivity (77%) and high
      specificity (64%) for ATN (P=0.002). Posttransplant plasma sIL-6R continued to be
      higher in ATN patients than in patients with normal biopsy (P=0.001). Patients
      with acute rejection showed pre- and posttransplant sIL-6R and TGF-beta2 plasma
      levels similar to those of patients with normal biopsy (P=NS). CONCLUSION: High
      pretransplant sIL-6R plasma levels are associated with an increased risk of ATN
      and might contribute to the development of ATN early posttransplant. Our data
      suggest that preactivation of the recipient's immune system increases the risk of
      ATN.

PMID- 16794540
TI  - Superior immunomodulatory effects of intravenous immunoglobulins on human T-cells
      and dendritic cells: comparison to calcineurin inhibitors.
AB  - BACKGROUND: Prophylactic administration of anti-HBs intravenous immunoglobulins
      (IVIg) in hepatitis B infected-liver transplant patients protects against acute
      rejection. To explore the suitability of intravenous immunoglobulins (IVIg) as
      prophylaxis of acute rejection and graft-versus-host disease (GVHD) after
      allograft transplantation, the effects of IVIg and calcineurin inhibitors (CNI)
      on human blood-derived T-cells and DC were compared. METHODS: T-cells were
      stimulated with phytohemagglutinin (PHA) or allogeneic spleen antigen-presenting
      cells (APC) and T-cell proliferation and cytokine production were determined in
      presence or absence of IVIg or CNI. Immature blood dendritic cells (DC) were
      stimulated in presence or absence of IVIg or CNI, and allogeneic T-cell
      stimulatory capacity, cell death, and phenotypic maturation were established.
      RESULTS: IVIg and CNI equally inhibited T-cell proliferation and IFN-gamma
      production after PHA stimulation or allogeneic stimulation. CD8+ T-cells were
      preferentially affected by both IVIg and CNI after allogeneic stimulation. Like
      CNI, addition of IVIg at later time points after T-cell activation suppressed
      mitotic progression of responding T-cells. IVIg-treated DC were suppressed in
      their capacity to stimulate allogeneic T-cell proliferation by 73+/-12%, whereas
      DC-function was not affected by CNI. The decreased allogeneic T-cell stimulatory
      capacity of IVIg-treated DC correlated to induction of cell death in DC and
      decreased up-regulation of CD40 and CD80. CONCLUSIONS: In vitro IVIg functionally
      inhibit the two principal immune cell-types involved in rejection and GVHD, i.e.
      T-cells and DC, whereas CNI only suppress T-cells. By targeting both T-cells and
      DC, IVIg may be a promising candidate for immunosuppressive treatment after
      allograft transplantation.

PMID- 16794541
TI  - How painful is donor nephrectomy? Retrospective analysis of early pain and pain
      management in open versus laparoscopic versus retroperitoneoscopic nephrectomy.
AB  - BACKGROUND: The aim of this study was to evaluate the early postoperative pain
      and pain management after standard open (ODN), hand-assisted laparoscopic (HLDN)
      and retroperitoneoscopic (RDN) donor nephrectomy. METHODS: The visual analogue
      scale (VAS) was determined twice a day in 203 donors during the first five days
      after nephrectomy. RESULTS: Mean VAS was significantly lower after RDN and HLDN
      than after ODN on day 2 (p=0.004) and days 3-5 (p<0.001). After RDN, "no pain"
      (VAS=0) was reported significantly earlier than after ODN. Irrespective of the
      technique used and the pain management, all donors reported significantly higher
      VAS in the morning. Opiates were administered for a significantly shorter average
      time period after RDN than after ODN (p=0.005). Cumulative morphine equivalent
      doses were higher after ODN than after RDN (p=0.001). Mean VAS reported after
      HLDN and RDN was similar. CONCLUSIONS: In summary, RDN and HLDN were clearly
      associated with much less early pain than ODN, independently of the used pain
      management.

PMID- 16794542
TI  - A case series of drotrecogin alfa (activated) in lung transplant recipients.
AB  - Severe sepsis in lung transplant recipients is a challenging problem and carries
      a high mortality. Recombinant human activated protein C (drotrecogin alfa
      [activated]) has been approved for use in patients with severe sepsis. Its use
      has been shown to be safe and impart a survival advantage. However, the safety of
      drotrecogin alfa activated has not been evaluated in lung transplant recipients.
      We report for the first time on the use of drotrecogin alfa activated in six lung
      transplant recipients. Clinical trials are warranted to further evaluate the use
      of drotrecogin alfa activated in transplant recipients.

PMID- 16794543
TI  - Pretransplant immunomodulation of highly sensitized small bowel transplant
      candidates with intravenous immune globulin.
AB  - Presence of preformed lymphocytotoxic antibodies may represent a barrier to
      isolated intestinal transplantation (IITx). We developed an intravenous
      immunoglobulins (IVIg) based desensitization protocol for candidates with high
      panel-reactive antibodies (PRA). Six patients with a mean PRA of 72+/-22% were
      included in a four-level (L) protocol with escalating doses of IVIg (L1, L2),
      addition of mycophenolate mofetil (MMF) or plasmapheresis (L3); and anti-CD20
      (Rituximab) (L4). Four of six candidates improved their PRAs (from a mean of
      66.2% to 25.5%; P=0.01) and were successfully transplanted. At a mean follow-up
      of 8 months, number and severity of rejection episodes of protocol patients did
      not differ from patients with low PRA transplanted during the same period. These
      data support the use of IVIg to desensitize patients waiting for IITx. It
      increases the applicability of IITx, and reduces the waiting time and mortality
      on the waiting list with outcomes comparable to nonsensitized recipients.

PMID- 16794544
TI  - Impact of double-filtration plasmapheresis in combination with interferon and
      ribavirin in living donor liver transplant recipients with hepatitis C.
AB  - Double-filtration plasmapheresis (DFPP) selectively removes high molecular weight
      substances including hepatitis C virus (HCV). Four live donor liver
      transplantation (LDLT) recipients with HCV received combination therapy with low
      dose interferon (IFN) and ribavirin with DFPP. Three patients underwent this
      therapy for prophylaxis of HCV recurrence, and one for treating fibrosing
      cholestatic hepatitis (FCH). The combination therapy and DFPP decreased HCV RNA
      levels to 8.2% +/- 2.9% and 0.7% +/- 0.5% by the 5th and 30th day of treatment,
      respectively. Three patients who underwent DFPP for prophylaxis showed no
      evidence of HCV recurrence for >1 year after treatment. The patient whose graft
      showed FCH, recovered dramatically after the DFPP treatment. DFPP appeared to be
      effective in reducing HCV viremia and preventing HCV recurrence in patients with
      high HCV RNA levels after LDLT. Moreover, it may become a rescue therapy for FCH
      in a liver transplant recipient with hepatitis C.

PMID- 16794545
TI  - Clinically relevant drug interaction between voriconazole and tacrolimus in a
      primary renal allograft recipient.

PMID- 16794546
TI  - Does using HTK solution for cold perfusion of cadaveric kidneys save money?

PMID- 16794547
TI  - Unusual T-cell repopulation after autologous stem cell transplantation for HIV
      associated lymphoma.

PMID- 16794548
TI  - Patient-delivered partner therapy for chlamydial infections: attitudes and
      practices of California physicians and nurse practitioners.
AB  - OBJECTIVE: The objective of this study was to examine California clinicians' use
      of and attitudes toward patient-delivered partner therapy (PDPT) to treat sexual
      partners of patients infected with chlamydia. STUDY DESIGN: In 2002, a stratified
      random sample of primary care physicians and nurse practitioners completed a
      mailed, self-administered survey. Weighted frequencies were calculated to assess
      partner management practices, including PDPT, and attitudes toward PDPT.
      Multivariate models were constructed to determine independent predictors of PDPT
      use. RESULTS: Of 708 physicians and 895 nurse practitioners, approximately half
      (47% and 48%, respectively) reported that they use PDPT usually or always. Over
      90% agreed that PDPT protects patients from reinfection and provides better care
      for patients with chlamydia. However, providers reported concerns that PDPT may
      result in incomplete care for the partner, may be dangerous without knowing the
      partner's medical or allergy history, is an activity the practice may not get
      paid for, and may get them sued. Obstetrics/gynecology and family practice
      physicians were more likely than internal medicine physicians to report routine
      use of PDPT. Concerns about adverse outcomes of PDPT were associated with less
      PDPT use. CONCLUSIONS: Although the proportion of California healthcare providers
      routinely using PDPT is comparatively high, further study is warranted to examine
      the circumstances under which this partner management strategy is used.

PMID- 16794550
TI  - Sexually transmitted infections and HIV in the southern United States: an
      overview.

PMID- 16794551
TI  - HIV/AIDS, sexually transmitted diseases, and incarceration among women: national
      and southern perspectives.
AB  - OBJECTIVE: The objective of this study was to explore the relationships between
      incarceration and emerging increases in HIV and sexually transmitted diseases
      (STDs) in the rural south, particularly among black women of low socioeconomic
      status. STUDY DESIGN: The study used secondary data on correctional populations,
      incarceration rates, admissions to correctional facilities (prisons and jails),
      HIV and STD prevalence among inmates, and national and state HIV surveillance
      data. RESULTS: Simultaneous consideration of these disparate data suggests some
      important patterns. Nationally, increasing proportions of inmates are women, and
      blacks and Latinos/as of low socioeconomic status are disproportionately
      represented in inmate populations. Incarceration rates are higher in the south
      (790 per 100,000) than in other regions and, within the south, rates are about
      the same for rural and urban counties (1194 and 1160). The prevalences of HIV and
      STDs are higher among female than male inmates (for HIV, approximately 3% to 2%
      nationally), and among the highest regional burdens of HIV are found among
      releasees from southern correctional facilities (26% of all people living with
      HIV in the south in 1999 were released from a prison or jail that same year) and
      among southern women releasees (15% of all women with HIV were correctional
      releasees). Taken together, these figures suggest that many southern women with
      HIV/AIDS and STDs, especially poor black women from rural areas, are found in
      prisons and jails, perhaps more so than in other parts of the country. At the
      same time, only small percentages of newly reported cases of AIDS among women in
      the south are diagnosed in correctional facilities (0.6-7%, depending on the
      state). CONCLUSIONS: Given the concentrations of rural black women with HIV/AIDS
      and STDs in southern correctional facilities, it is important to recognize that
      prisons and jails are critical settings in which to deploy programs for the
      prevention, diagnosis, and treatment of infectious diseases and other health
      problems. Such interventions, as well as interventions focused on the rural
      communities themselves, would benefit not only inmates and releasees, but also
      the larger public health.

PMID- 16794552
TI  - Diffusion of innovations and network segmentation: the part played by people in
      promoting health.
AB  - OBJECTIVE: The objective of this study was to describe how diffusion of
      innovations theory can integrate mass media, interpersonal communication, and
      social network analysis. These principles can be used to implement and tailor
      data-based health promotion activities. GOAL: The goal of this study was to
      develop a model for using and incorporating interpersonal communication into
      health promotion programs designed to encourage behaviors that reduce the spread
      of sexually transmitted diseases (STDs)/HIV. STUDY DESIGN: The authors conducted
      a review of selected studies that exemplify how diffusion of innovations theory
      has applied interpersonal communication to promote STD/HIV preventive health
      behaviors. RESULTS: Few studies have incorporated interpersonal communication as
      an intervention strategy to encourage STD/HIV preventive behavior. Interventions
      that have used interpersonal communication have observed successes in health
      promotion and increases in safer sex behaviors. CONCLUSIONS: This study shows
      that social network analysis can be used to design more appropriate and perhaps
      more effective health promotion programs.

PMID- 16794553
TI  - The epidemiology of HIV/AIDS in women in the southern United States.
AB  - OBJECTIVE: We reviewed data from multiple sources to examine distinguishing
      features of the HIV epidemic among women in the South. GOAL: The goal of this
      study was to identify HIV and sexually transmitted disease (STD) prevention
      research priorities in the South. STUDY DESIGN: Cases of HIV/AIDS and STDs were
      analyzed to compare rates by region and rates in urban versus rural areas. Data
      from interviews of persons reported with HIV/AIDS from rural areas in 4 southern
      states compared social and behavioral characteristics of men versus women.
      RESULTS: The South is characterized by high AIDS and STD rates. The epidemic
      among southern women is distinguished by the predominance of heterosexually
      acquired infection, the disproportionate impact on blacks, the high proportion
      residing in rural areas, and multiple high-risk behaviors. CONCLUSIONS: Research
      to identify determinants of high-risk sex and drug-using behaviors among poor,
      minority men and women in less urban and rural southern regions is needed.

PMID- 16794554
TI  - HIV and African Americans in the southern United States: sexual networks and
      social context.
AB  - BACKGROUND: Heterosexual HIV transmission among African Americans in the rural
      southern United States has climbed in recent years. Concurrent partnerships and
      bridge populations have emerged as key elements in the spread of sexually
      transmitted infections (STIs). GOAL: The goal of this study was to examine
      published empiric data and other literature concerning the extent of these
      network patterns and their relationship to the socioeconomic context among
      African Americans in the rural South. STUDY DESIGN: The authors conducted a
      review of public health, medical, and social sciences literature. RESULTS: In
      areas of the rural South with high STI rates, there is extensive concurrency with
      evidence of dense sexual networks and bridging among the general population, core
      group members, and other high-risk subpopulations. Qualitative research reveals
      socioeconomic factors that support these network patterns: low ratio of men to
      women, economic oppression, racial discrimination, and high incarceration rates
      of black men. CONCLUSION: Concurrency and bridging likely contribute to increased
      heterosexual HIV transmission among blacks in the South; contextual factors
      promote these network patterns in this population.

PMID- 16794555
TI  - Structural interventions to prevent HIV/sexually transmitted disease: are they
      cost-effective for women in the southern United States?
AB  - BACKGROUND: Structural interventions are theoretically promising for populations
      with a low prevalence of HIV, because they can reach large numbers of people to
      influence their social norms and collective risky behaviors for a relatively low
      cost per person. Because HIV transmission is continuing to increase among women
      in the southern United States, interventions to stem this epidemic are
      particularly warranted. This study explores whether structural interventions may
      be a cost-effective way to prevent HIV in this population. METHODS: We used the
      cost-effectiveness estimator, "Maximizing the Benefit" to determine the relative
      cost-effectiveness of 6 structural HIV prevention interventions. "Maximizing the
      Benefit" is a spreadsheet tool using mathematical models to estimate the cost per
      HIV infection prevented taking into account the epidemiologic contexts,
      behavioral change as a result of an intervention, and the costs of intervention.
      We applied estimates of HIV prevalence related to blacks in the southern United
      States. RESULTS: All the structural interventions were cost-effective compared
      with average lifetime treatment costs of HIV, but mass media, condom
      availability, and alcohol taxes theoretically prevented the largest numbers of
      HIV infections. CONCLUSIONS: Although the assumptions used in cost-effectiveness
      estimates have many limitations, they do allow for a relative comparison of
      different interventions and help to inform policy decisions related to the
      allocation of HIV prevention resources. Structural interventions hold the
      greatest promise in reducing HIV transmission among low-prevalence populations.

PMID- 16794556
TI  - From slavery to incarceration: social forces affecting the epidemiology of
      sexually transmitted diseases in the rural South.
AB  - The high rates of sexually transmitted diseases (STDs) in the southeastern United
      States have been shaped by historic and contemporary social forces. More than
      other regions of the country, the South was defined by slavery, an extremely
      hierarchical relationship between whites and blacks. Emancipation left much of
      the racial hierarchy intact with whites as farm owners and blacks as hired
      workers or sharecroppers. Agricultural policies that favored mechanization caused
      blacks to leave farm work and move into segregated towns, leading to the advent
      of the rural ghetto. Post-World War II mass migration, mostly by young men, to
      the industrial north altered the sex ratio and social capital of the southern
      towns left behind. The cocaine epidemic of the 1990s, followed by the high
      incarceration rates of the "War on Drugs," disproportionately affected low-income
      blacks. Each of these forces led to sexual and care-seeking behaviors that favor
      transmission of STDs.

PMID- 16794557
TI  - Racial disparities in care: the concealed legacy of a divided system.
AB  - BACKGROUND AND OBJECTIVES: New national initiatives to end racial disparities in
      health could benefit from the experience with Title VI enforcement in the
      Medicare Program. GOALS: The goals of this study were to describe events in a
      test case to extend Medicare Title VI conditions for hospitals to the practice
      patterns of its medical staff and how the outcome shaped disparities. METHOD:
      This article distills interviews, archives, and secondary data sources. STUDY
      DESIGN: This study is an historical narrative. RESULTS: The test case was a
      costly failure. Although the Title VI effort eliminated segregation on hospital
      floors and equalized overall use, physician practice patterns were left
      unexamined, contributing to the persistence of disparities in treatment.
      CONCLUSIONS: If current efforts are to be successful, they will need to 1)
      address the structural issues that shape disparities, 2) pay particular attention
      to reengineering care in ways that overcome historic patterns, and 3) ensure a
      greater degree of accountability.

PMID- 16794558
TI  - Congenital syphilis: a persisting sentinel public health event.

PMID- 16794559
TI  - Hospitalization for pelvic inflammatory disease: a cost-effectiveness analysis.
AB  - OBJECTIVE: Nulliparous women are frequently hospitalized for treatment of pelvic
      inflammatory disease (PID). GOAL: The goal of this study was to determine the
      economic feasibility of hospitalizing adolescents and young women for PID. STUDY
      DESIGN: The authors conducted a Markov decision model, estimating the cost
      effectiveness of hospitalization compared with outpatient therapy for mild to
      moderate PID for adolescents and young women, calculating costs per quality
      adjusted life-year (QALY) gained under various assumptions about hospitalization
      effects on complications. RESULTS: If hospitalization decreases PID complications
      by 10%, 20%, or 30%, the cost/QALY gained is 145,000 dollars, 67,400 dollars, or
      42,400 dollars, respectively, compared with outpatient therapy. Assumptions about
      hospitalization effects on the development of chronic pelvic pain heavily weight
      the analysis; costs/QALY gained by hospitalization increase considerably if
      chronic pain is unaffected. CONCLUSION: Hospitalization for PID treatment to
      possibly preserve fertility in nulliparous young women and adolescents is
      unlikely to be economically reasonable even if substantial improvements in PID
      complication rates are assumed.

PMID- 16794560
TI  - Postexposure prophylaxis for HIV in children and adolescents after sexual
      assault: a prospective observational study in an urban medical center.
AB  - BACKGROUND: We sought to evaluate the tolerability and feasibility of
      establishing an HIV postexposure prophylaxis (PEP) program at our hospital using
      the guidelines for children and adolescents after sexual assault. METHODS: This
      study was a prospective, nonrandomized observational study conducted from March
      1999 until September 2002. Subjects (age <19 years) who presented to a pediatric
      emergency room within 72 hours of a sexual assault were eligible for enrollment.
      A 28-day PEP regimen of zidovudine and lamivudine was given. RESULTS: In all, 70
      adolescents were evaluated and 33 (31 females and 2 males) were enrolled. The
      mean age of enrolled subjects was 15 years, 61% were Hispanic, 30% black, and 79%
      presented to the emergency room within 24 hours of assault. Vaginal exposure was
      the most common site of penetration (64% [21 of 33]), but 18% (6 of 33) reported
      anal penetration. Only 9 subjects (27%) took >or=90% of all the medications. All
      subjects who returned for follow up tested HIV-negative. Adverse events occurred
      in 48% (16 of 33) of subjects; the most common events were abdominal pain,
      nausea, or vomiting. CONCLUSION: Poor adherence to medications and visits is a
      significant problem in PEP programs for sexually assaulted children and
      adolescents.

PMID- 16794561
TI  - Blockade of 5-HT2a receptors reduces haloperidol-induced attenuation of reward.
AB  - Previous studies have shown that effective antipsychotic medications attenuate
      reward, an effect that is generally attributed to their effectiveness at blocking
      the dopamine D2-like receptors. As blockade of the serotonin type 2a (5-HT2a)
      receptors is a common property of the newer antipsychotics, the present study
      compared the effect of haloperidol, clozapine, and M100907 (a selective 5-HT2a
      antagonist) and the combined effect of haloperidol and M100907 treatment on brain
      stimulation reward (BSR). Experiments were performed on male Sprague-Dawley rats
      trained to produce an operant response to obtain electrical stimulation in the
      lateral hypothalamus. Measures of reward threshold were determined in different
      groups of rats using the curve-shift method using fixed current intensity and
      variable frequency before and at different times after injection of haloperidol
      (0.01, 0.05, 0.1, and 0.25 mg/kg), clozapine (1, 7.5, 15, and 30 mg/kg), M100907
      (0.033, 0.1, and 0.3 mg/kg), or their vehicle. The effect of M100907 (0.3 mg/kg)
      on the attenuation of BSR by a sub- and suprathreshold dose of haloperidol was
      studied in another group of rats. Clozapine produced a dose-orderly increase in
      reward threshold with a mean maximal increase of 50%; at high doses, clozapine
      induced cessation of responding in several animals at different time periods.
      Haloperidol induced a dose-dependent increase in reward threshold, with the mean
      maximal increase (75%) being observed at the highest dose; it also produced a
      dose-dependent reduction of maximum rates of responding. M100907 failed to alter
      reward at any of the doses tested and had no effect on the subthreshold dose
      (0.01 mg/kg) of haloperidol. But when combined with a suprathreshold dose of
      haloperidol, M100907 reduced the reward-attenuating effect of haloperidol. These
      results show that 5-HT2a receptors are unlikely to constitute a component of the
      reward-relevant pathway activated by lateral hypothalamic stimulation. However,
      blockade of 5-HT2a receptors may account for the relatively lower level of reward
      attenuation produced by clozapine, and predict that antipsychotic medications
      that have a high affinity for the 5-HT2a receptor may be less likely to induce
      dysphoria.

PMID- 16794562
TI  - Acquisition of nicotine self-administration in adolescent rats given prolonged
      access to the drug.
AB  - As most human tobacco use begins during adolescence and ongoing development of
      the adolescent central nervous system could affect acquisition of nicotine self
      administration (SA), our established rat SA procedure was modified to study
      adolescent acquisition of SA with prolonged access to nicotine (23 h/day).
      Postnatal age 43-45 female Lewis rats, without prior shaping, conditioning, or
      food deprivation, were housed in operant chambers equipped with two levers;
      pressing the active lever triggered an i.v. injection of nicotine. By the 10th
      day of SA, rats receiving 7.5, 15, 30, or 60 microg/kg/injection nicotine (free
      base) obtained 23+/-16, 50+/-8, 65+/-8, or 48+/-5 injections (mean+/-SE),
      respectively. In the 30 microg/kg/injection group, active : inactive ratio was
      greater than 2 after SA day 4; 92% of injections occurred during the 12-h active
      (dark) phase of the light cycle. Main effects (analysis of variance) were shown
      for day and lever (ie active vs inactive) (p<0.001). Adolescent males showed
      similar dose-dependent nicotine SA. With the increasing workload imposed by
      raising the fixed ratio (FR), less nicotine was self-administered at FR 5 and 7
      compared to FR 1 and 3. In comparison to adult females self-administering 30
      microg/kg/injection of nicotine at FR 1, adolescents acquired nicotine SA at an
      accelerated rate (p<0.05) and received a greater number of injections (p<0.05) by
      day 10. In conclusion, when given prolonged access to the drug, both female and
      male adolescent Lewis rats rapidly acquire nicotine SA within the dosage range
      and FR constraints previously observed in adult Lewis rats. However, adolescent
      females acquired the behavior more rapidly and attained higher levels of stable
      nicotine SA than adults.

PMID- 16794563
TI  - Regulation by nicotine of Gpr51 and Ntrk2 expression in various rat brain
      regions.
AB  - Our previous genetic studies demonstrated that variants of the gamma-Aminobutyric
      acid B receptor subunit 2 (GPR51) and neurotrophic tyrosine kinase receptor type
      2 (NTRK2) genes are significantly associated with nicotine dependence (ND) in
      smokers. However, whether such genetic associations lead to changes in the
      expression of the two genes in response to nicotine remains undetermined. In this
      study, we investigated the regulatory effect of nicotine on the expression of
      Gpr51 and Ntrk2 in seven rat brain regions during the administration of nicotine
      in a daily dose of 3.15 mg/kg for 7 days. With quantitative real-time RT-PCR, we
      found that nicotine increased the mRNA of Gpr51 by 70, 78, and 32% in the
      amygdala, striatum, and prefrontal cortex (PFC), respectively, but decreased by
      54% in the nucleus accumbens (NA). The Gpr51 protein was upregulated by nicotine
      in the amygdala (26%), striatum (73%), PFC (28%), and medial basal hypothalamus
      (MBH; 19%) but downregulated in the NA (-72%). Similarly, the mRNA level of Ntrk2
      was enhanced by nicotine in the striatum (86%) and PFC (38%), but decreased in
      the NA (-46%) and ventral tegmental area (VTA; -49%). A significant change in
      protein expression was also obtained for Ntrk2 in the PFC (24%), MBH (33%), NA (
      33%), and VTA (-70%). Interestingly, these two genes showed a closely coordinated
      expression pattern in response to nicotine in most of the brain regions examined.
      In summary, our results demonstrate that the expression of Gpr51 and Ntrk2 is
      significantly regulated by nicotine at both the mRNA and protein levels in
      various brain regions, which provides further evidence that these two genes are
      involved in the etiology of ND, as reported in our previous genetic association
      studies in humans.

PMID- 16794564
TI  - The selective mGlu5 receptor antagonist MTEP, similar to NMDA receptor
      antagonists, induces social isolation in rats.
AB  - It has repeatedly been shown that uncompetitive N-methyl-D-aspartate (NMDA)
      receptor antagonists can mimic certain aspects of positive and negative symptoms
      of schizophrenia in human volunteers and laboratory animals. The purpose of the
      present study was to expand these findings and to determine whether the selective
      metabotropic glutamate receptor subtype 5 (mGluR5) antagonist, MTEP (3-[(2-methyl
      1,3-thiazol-4-yl)ethynyl]pyridine), could induce similar effects in Wistar rats.
      First, MTEP (1.0-10.0 mg/kg; intraperitoneally) after acute and subchronic (daily
      for 5 days) administration as well as the uncompetitive antagonists of the NMDA
      receptor of either high affinity, phencyclidine (0.5-4.0 mg/kg; subcutaneously
      (s.c.)) and (+)-MK-801 (0.03-0.25 mg/kg; s.c.), or low-moderate affinity,
      ketamine (2.0-16.0 mg/kg; s.c.) and memantine (0.15-20.0 mg/kg; s.c.), following
      daily administration for 3 days were tested in the social interaction test to
      determine their ability to reproduce the negative and positive symptoms measured
      by social isolation and stereotyped behavior, respectively. Second, the compounds
      were tested in the motility test following acute administration to determine
      their ability to induce locomotor hyperactivity reflecting the positive symptoms.
      In line with previous findings, all examined NMDA receptor antagonists produced
      social interaction deficits, locomotor hyperactivity, and stereotypy except
      memantine. Notably, this study found that MTEP following both acute and
      subchronic administration dose-dependently induced social isolation, but did not
      cause either locomotor hyperactivity or stereotypy. These data demonstrate that
      social behavior deficits in rats can be caused by both the blockade of the NMDA
      receptor and the inhibition of mGluR5, whereas mGluR5 antagonists may not
      independently be able to mimic the positive symptoms.

PMID- 16794565
TI  - The effect of early poststressor intervention with sertraline on behavioral
      responses in an animal model of post-traumatic stress disorder.
AB  - Whereas several well-controlled studies have established the selective serotonin
      reuptake inhibitors (SSRIs) as the recommended first-line pharmacotherapeutic
      agents for acute and chronic post-traumatic stress disorder (PTSD), drug
      interventions in the acute postexposure phase have not been studied to the same
      extent and tend to be largely speculative. This study employed an animal model
      which assesses prevalence of individual stress-response behavior patterns in
      order to assess the short-term effects of a brief treatment regimen with an SSRI
      (sertraline) administered immediately after stress-exposure, with those of an
      identical delayed regimen and of saline. Prevalence rates of rats displaying
      extreme anxiety-like behavioral responses to predator stress, compared to partial
      and minimal responses, were assessed in the elevated plus maze and startle
      response paradigms, with and without intraperitoneal administration of sertraline
      for 7 days immediately postexposure, or 7 days after exposure. Immediate
      postexposure administration of sertraline reduced anxiety-like and avoidant
      behavior, decreased hyperarousal responses and diminished the overall incidence
      of extreme (PTSD-like) behavioral responses, compared to the delayed treatment
      regimen and to saline controls. Brief immediate poststress exposure treatment
      with sertraline reduced prevalence rates of extreme behavioral disruption in the
      short-term. SSRI drugs are thus worthy of further investigation as agents of
      secondary prevention in the acute aftermath of stress-exposure.

PMID- 16794566
TI  - Report by the ACNP Task Force on response and remission in major depressive
      disorder.
AB  - This report summarizes recommendations from the ACNP Task Force on the
      conceptualization of remission and its implications for defining recovery,
      relapse, recurrence, and response for clinical investigators and practicing
      clinicians. Given the strong implications of remission for better function and a
      better prognosis, remission is a valid, clinically relevant end point for both
      practitioners and investigators. Not all depressed patients, however, will reach
      remission. Response is a less desirable primary outcome in trials because it
      depends highly on the initial (often single) baseline measure of symptom
      severity. It is recommended that remission be ascribed after 3 consecutive weeks
      during which minimal symptom status (absence of both sadness and reduced
      interest/pleasure along with the presence of fewer than three of the remaining
      seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved,
      remission can only be lost if followed by a relapse. Recovery is ascribed after
      at least 4 months following the onset of remission, during which a relapse has
      not occurred. Recovery, once achieved, can only be lost if followed by a
      recurrence. Day-to-day functioning and quality of life are important secondary
      end points, but they were not included in the proposed definitions of response,
      remission, recovery, relapse, or recurrence. These recommendations suggest that
      symptom ratings that measure all nine criterion symptom domains to define a major
      depressive episode are preferred as they provide a more certain ascertainment of
      remission. These recommendations were based largely on logic, the need for
      internal consistency, and clinical experience owing to the lack of empirical
      evidence to test these concepts. Research to evaluate these recommendations
      empirically is needed.

PMID- 16794567
TI  - Behavioral and neurochemical responses to cocaine in periadolescent and adult
      rats.
AB  - Although recreational drug use by human adolescents is a well-known and long
      standing problem, relatively little is known regarding differences in behavioral
      and physiological responses to abused substances in adolescent vs adult animals.
      The present study compared effects of the psychomotor stimulant, cocaine, in
      periadolescent (postnatal days 37-52) and adult (postnatal days 75-90) male
      Wistar rats. Locomotion and motor stereotypy were recorded after acute and
      repeated cocaine injections (0, 10, or 20 mg/kg cocaine, intraperitoneal (i.p.),
      four injections spaced 5 days apart). Spontaneous acquisition of intravenous
      (i.v.) cocaine self-administration was investigated in two dose groups (
      approximately 0.37 or 0.74 mg/kg/infusion) over 14 days. Dopamine levels in the
      nucleus accumbens were recorded under basal conditions (no net flux method) and
      after cocaine administration ( approximately 0.37, 0.74, and 2.92 mg/kg/i.v.
      infusion or 20 mg/kg i.p.) using in vivo microdialysis. The locomotor data are in
      partial agreement with previous reports of hyposensitivity to acute cocaine in
      periadolescent vs adult rats; periadolescents were less active overall than
      adults. Moreover, adult rats exhibited significant locomotor sensitization after
      repeated injection of 10 mg/kg cocaine, whereas periadolescents required the high
      dose of 20 mg/kg cocaine to demonstrate sensitization. Neither age group showed
      sensitization of motor stereotypies. No age-related difference was observed in
      acquisition of cocaine self-administration, or in basal or cocaine-stimulated
      nucleus accumbens dopamine. These experiments imply a developmental dissociation
      between the motor activating and reinforcing effects of cocaine. Similarities in
      dopamine levels across age groups suggest that age-specific motor responses to
      cocaine are not mediated by dopamine in the nucleus accumbens.

PMID- 16794568
TI  - Mecamylamine attenuates cue-induced reinstatement of nicotine-seeking behavior in
      rats.
AB  - Mecamylamine, a noncompetitive nicotinic cholinergic antagonist, inhibits
      nicotine self-administration in animals and may attenuate tobacco smoking in
      humans trying to quit. Our preliminary data suggested that this agent, at a dose
      of 2 mg/kg (subcutaneous (s.c.)), also attenuates cue-induced relapse to nicotine
      seeking behavior in rats. This study determined whether mecamylamine-induced
      attenuation can be obtained at doses lower than the high 2 mg/kg dose used in the
      first study, and whether it is specific to nicotine-associated cues. Male Sprague
      Dawley rats were trained to intravenously self-administer nicotine (0.03
      mg/kg/infusion) on a fixed-ratio 5 schedule. Each infusion was accompanied by a
      visual cue (1 s onset of a lever light followed by offset of a house light for 20
      s during which time no infusions could be obtained). After the nicotine
      maintained responding was extinguished by withholding the delivery of nicotine
      (saline substitution) and its associated cue, reinstatement tests were conducted.
      Response-contingent re-presentation of the cue without further availability of
      nicotine significantly reinstated extinguished responding at the previously
      nicotine-reinforced lever. Pretreatment with mecamylamine (0.5, 1, and 2 mg/kg,
      s.c.) dose-dependently attenuated the cue-induced reinstatement of lever
      responding. Mecamylamine did not change food-taking and -seeking responses,
      whereas the highest dose (2 mg/kg) decreased nicotine self-administration
      behavior. The results confirm previous findings that stimuli conditioned to
      nicotine self-administration effectively elicit reinstatement of nicotine-seeking
      behavior after extinction and demonstrate that mecamylamine, besides suppressing
      self-administration of nicotine, effectively attenuates cue-induced nicotine
      seeking behavior. These findings suggest that the response-reinstatement
      procedures used in this study may be useful for studying neurobiological
      mechanisms of nicotine-seeking behavior and that mecamylamine-like drugs may be
      potential candidates for pharmacological treatment and prevention of relapse to
      tobacco smoking in abstinent smokers.

PMID- 16794569
TI  - Altered levels of basal cortisol in healthy subjects with a 118G allele in exon 1
      of the Mu opioid receptor gene.
AB  - The mu opioid receptor is centrally involved in the development of the addictive
      diseases. It also modulates the stress responsive hypothalamic-pituitary-adrenal
      axis. Receptors encoded by the variant 118G polymorphism in exon 1 of the mu
      opioid receptor gene have a threefold increase in beta-endorphin binding and beta
      endorphin is three times more potent in receptor-mediated activation of G protein
      coupled inwardly rectifying potassium channels. Humans with this variant have
      increased stress response following opioid antagonism. Here, we study basal
      levels of adrenocorticotropic hormone and cortisol in subjects with this variant.
      In all, 59 healthy adults were genotyped and had morning levels of
      adrenocorticotropic hormone and cortisol measured following intravenous
      administration of saline placebo. Subjects with a 118G allele had significantly
      greater levels of cortisol than subjects with the prototype gene. Groups did not
      differ in levels of adrenocorticotropic hormone. A planned comparison revealed
      significantly greater cortisol in females with at least one copy of the 118G
      allele compared to females with the prototype gene. There was no significant
      effect of gender alone, nor was there a significant interaction between gender
      and genotype, on ACTH or cortisol. Subjects with at least one copy of the 118G
      allele have increased basal levels of cortisol, which may influence the
      susceptibility to and treatment of the stress responsive dyscrasia.

PMID- 16794570
TI  - Modulation of human motor cortex excitability by single doses of amantadine.
AB  - Amantadine-sulfate has been used for several decades to treat acute influenza A,
      Parkinson's disease (PD), and acute or chronic drug-induced dyskinesia. Several
      mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate
      (NMDA)-receptor antagonism, blockage of potassium channels, dopamine receptor
      agonism, enhancement of noradrenergic release, and anticholinergic effects have
      been described. We used transcranial magnetic stimulation (TMS) to evaluate the
      effect of single doses of amantadine on human motor cortex excitability in normal
      subjects. Using a double-blind, placebo-controlled, crossover study design, motor
      thresholds, recruitment curves, cortical stimulation-induced silent period (CSP),
      short intracortical inhibition (ICI), intracortical facilitation (ICF), and late
      inhibition (L-ICI) in 14 healthy subjects were investigated after oral doses of
      50 and 100 mg amantadine with single and paired pulse TMS paradigms. Spinal cord
      excitability was investigated by distal latencies and M-amplitudes of the
      abductor digiti minimi muscle. After intake of amantadine, a significant dose
      dependent decrease of ICF was noticed as well as a significant increase of L-ICI
      as compared to placebo. The effect on ICF and L-ICI significantly correlated with
      amantadine serum levels. ICI was slightly increased after amantadine intake, but
      the effect failed to be significant. Furthermore, amantadine had no significant
      effects on motor thresholds, MEP recruitment curves, CSP, or peripheral
      excitability. In conclusion, a low dose of amantadine is sufficient in modulating
      human motor cortex excitability. The decrease of ICF and increase of L-ICI may
      reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic
      and GABA-ergic circuits. Although amantadine has several mechanisms of action,
      the NMDA-receptor antagonism seems to be the most relevant effect on cortical
      excitability. As L-ICI can be influenced by this type of drug, it may be an
      interesting parameter for studies of motor learning and use-dependent plasticity.

PMID- 16794571
TI  - Previous exposure to cocaine enhances cocaine self-administration in an alpha 1
      adrenergic receptor dependent manner.
AB  - Noradrenergic transmission is implicated in the biochemical and behavioral
      effects of cocaine. Recently, we demonstrated that the alpha 1-adrenergic
      receptor antagonist prazosin attenuates cocaine-induced reinstatement of drug
      seeking behavior. We now assessed whether prazosin could counter the effect of
      previous exposure to cocaine to enhance subsequent self-administration behavior.
      Rats were pre-exposed to systemic injections of either saline, prazosin (0.3
      mg/kg), saline+cocaine (10 mg/kg), or prazosin+cocaine for 5 days. Starting 15-18
      days after the last pre-exposure injection, rats were trained to self-administer
      cocaine (0.5 mg/kg/infusion) under a fixed ratio 3 (FR3) schedule of
      reinforcement. Several tests were conducted. First, responding for cocaine under
      an FR3 schedule was assessed across several doses (0.125-1.0 mg/kg/infusion).
      Second, responding for cocaine (0.5 mg/kg/infusion) under a progressive-ratio
      (PR) schedule was examined for 6 consecutive days. Finally, responding for
      cocaine (0, 0.5, and 1.0 mg/kg/infusion) was determined under the PR schedule of
      reinforcement. Results showed that cocaine pre-exposed rats self-administer more
      cocaine compared to saline pre-exposed rats when tested under both the FR and PR
      schedules. Rats pre-exposed to cocaine plus prazosin did not show enhanced
      cocaine self-administration. These rats, as well those pre-exposed to prazosin
      alone, showed levels of cocaine self-administration similar to saline pre-exposed
      rats. Thus, previous exposure to cocaine enhanced cocaine self-administration, an
      effect that appears to involve activation of alpha 1-adrenergic receptors. These
      data, along with several recent studies, show further support for the
      contribution of noradrenergic transmission in the behavioral effects of cocaine.

PMID- 16794572
TI  - Omega-3 fatty acid ethyl-eicosapentaenoate attenuates IL-1beta-induced changes in
      dopamine and metabolites in the shell of the nucleus accumbens: involved with
      PLA2 activity and corticosterone secretion.
AB  - Previously, we have reported that interleukin-1 beta (IL-1) induces changes in
      dopaminergic (DA) and serotonergic systems in the core of the [corrected] nucleus
      accumbens (NAc). We have also demonstrated that n-3 fatty acid ethyl
      eicosapentaenoate (EPA) can significantly reduce stress and anxiety-like
      behaviors, corticosterone concentrations [corrected] and peripheral inflammatory
      response induced by IL-1 administration. Compared to the core, the shell is
      involved more in emotion, stress and psychiatric diseases. However, the
      relationship between inflammation and the functions of DA system in the shell has
      not been studied. Since phospholipase (PL) A2 is a key enzyme in the [corrected]
      arachidonic acid-eicosanoids-prostaglandin [corrected] (PG)E2 pathway, and the
      change in NAc DA [corrected] system has been associated with glucocorticoid
      stimulation; [corrected] therefore, the hypotheses of this study are (1) that IL
      1 induced changes in DA neurotransmission in the shell may be through PLA2-PGE2
      corticosterone pathway; (2) EPA may attenuate IL-1 effects via inhibiting PLA2
      activities, which blocks PGE2 stimulation of corticosterone. Using an in vivo
      microdialysis method, the present study showed that IL-1 administration
      significantly increased extracellular levels of DA, and its metabolites 3,4
      dihydroxyphenylacetic acid, [corrected] and homovanillic acid [corrected] in the
      shell of the NAc. IL-1 also increased blood concentration of corticosterone and
      PGE2, and increased the activities of cytosolic and secretory [corrected] PLA2.
      IL-1-induced changes were significantly attenuated by EPA treatment. Furthermore,
      glucocorticoid [corrected] receptor antagonist mifepristone (RU486) pretreatment
      significantly blocked IL-1-induced changes in DA and metabolites. Quinacrine,
      [corrected] a PLA2 antagonist significantly blocked IL-1-induced [corrected]
      increase in PGE2 and corticosterone concentrations. These results demonstrated
      the hypotheses that IL-1 effects may be via PLA2-PGE2-corticosterone pathway and
      EPA attenuated IL-1 effects may be through the suppression of PLA2 expression,
      which then reduced PGE2 synthesis and corticosterone secretion.

PMID- 16794573
TI  - Effects of topiramate on the prepulse inhibition of the acoustic startle in rats.
AB  - The anticonvulsant topiramate (TPM) has been recently proposed as a novel
      adjuvant therapy for bipolar disorder and schizophrenia, yet its efficacy remains
      controversial. As both disorders are characterized by gating deficits, we tested
      the effects of TPM on the behavioral paradigm of prepulse inhibition (PPI) of the
      acoustic startle response, a validated animal model of sensorimotor gating. TPM
      (10, 18, 32, 58, 100 mg/kg, intraperitoneal, i.p.) enhanced PPI in rats in a dose
      dependent fashion, prevented the PPI reduction mediated by the dopaminergic
      agonist apomorphine (0.25 mg/kg, subcutaneous, s.c.) and potentiated the effects
      of the antipsychotic drugs haloperidol (0.05, 0.1 mg/kg, i.p.) and clozapine
      (2.5, 5 mg/kg, i.p.). Conversely, TPM elicited no significant effect on the PPI
      disruption mediated by the NMDA receptor antagonist dizocilpine (0.05, 0.1 mg/kg,
      s.c.) and surprisingly antagonized the attenuation of dizocilpine-induced PPI
      disruption mediated by clozapine (5 mg/kg, i.p.). Our results suggest that TPM
      may exert diverse actions on the neural substrates of sensorimotor gating. While
      the pharmacological mechanisms of such effects are still elusive, our findings
      might contribute to shed light on some controversies on the therapeutic action of
      TPM, and point to this drug as a putative novel adjuvant therapy for some
      clusters of gating disturbances.

PMID- 16794574
TI  - Reversal of cocaine-induced behavioral sensitization and associated
      phosphorylation of the NR2B and GluR1 subunits of the NMDA and AMPA receptors.
AB  - Cocaine abusers remain vulnerable to drug craving and relapse for many years
      after abstinence is achieved. We have recently shown that ondansetron (a 5-HT3
      receptor antagonist) given 3.5 h after each daily cocaine injection reverses
      previously established behavioral sensitization. The purpose of the present
      investigation was two-fold. First, as cocaine cannot be used as therapy, we
      examined whether pergolide (a D1/D2 receptor agonist with reduced abuse
      potential) and ondansetron could reverse behavioral sensitization. Second, we
      investigated whether these behavioral changes were associated with parallel
      alterations in expression levels and/or phosphorylation changes in the NR2B and
      GluR1 subunits of the respective NMDA and AMPA receptors. Rats were injected for
      5 consecutive days with cocaine or saline followed by 9 days of withdrawal.
      Starting on withdrawal day 10, animals were given vehicle, pergolide/saline, or
      pergolide/ondansetron for 5 consecutive days. Following a second 9-day period of
      withdrawal, all animals were challenged with cocaine for assessment of behavioral
      sensitization and tissues were collected on the following day for Western blot.
      Sensitization was associated with increased NR2B expression in the accumbens
      (NAc) shell and decreased Tyr1472 phosphorylation in the NAc core, as well as
      increased Ser845 phosphorylation of the GluR1 subunit in prefrontal cortex, NAc
      core, and shell. Pergolide/ondansetron treatment, but not pergolide alone,
      consistently reversed both the behavioral sensitization and the associated
      changes in the NMDA and AMPA receptor subunits. To the extent that sensitization
      plays a role in chronic cocaine abuse, a combination of these clinically
      available drugs may be useful in treatment of the disorder.

PMID- 16794575
TI  - Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop
      exchange.
AB  - The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the
      replication checkpoint. Chk2 activation is initiated by phosphorylation of Thr68,
      in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM. The
      phosphorylated SCD-segment binds to the FHA domain of a second Chk2 molecule,
      promoting dimerisation of the protein and triggering phosphorylation of the
      activation segment/T-loop in the kinase domain. We have now determined the
      structure of the kinase domain of human Chk2 in complexes with ADP and a small
      molecule inhibitor debromohymenialdisine. The structure reveals a remarkable
      dimeric arrangement in which T-loops are exchanged between protomers, to form an
      active kinase conformation in trans. Biochemical data suggest that this dimer is
      the biologically active state promoted by ATM-phosphorylation, and also suggests
      a mechanism for dimerisation-driven activation of Chk2 by trans-phosphorylation.

PMID- 16794576
TI  - Sterols regulate ER-export dynamics of secretory cargo protein ts-O45-G.
AB  - Alterations in endoplasmic reticulum (ER) cholesterol are fundamental for a
      variety of cellular processes such as the regulation of lipid homeostasis or
      efficient protein degradation. We show that reduced levels of cellular sterols
      cause a delayed ER-to-Golgi transport of the secretory cargo membrane protein ts
      O45-G and a relocation to the ER of an endogenous protein cycling between the ER
      and the Golgi complex. Transport inhibition is characterized by a delay in the
      accumulation of ts-O45-G in ER-exit sites (ERES) and correlates with a reduced
      mobility of ts-O45-G within ER membranes. A simple mathematical model describing
      the kinetics of ER-exit predicts that reduced cargo loading to ERES and not the
      reduced mobility of ts-O45-G accounts for the delayed ER-exit and arrival at the
      Golgi. Consistent with this, membrane turnover of the COPII component Sec23p is
      delayed in sterol-depleted cells. Altogether, our results demonstrate the
      importance of sterol levels in COPII mediated ER-export.

PMID- 16794577
TI  - Genetic linkage of pfmdr1 with food vacuolar solute import in Plasmodium
      falciparum.
AB  - The P-glycoprotein homolog of the human malaria parasite Plasmodium falciparum
      (Pgh-1) has been implicated in decreased susceptibility to several antimalarial
      drugs, including quinine, mefloquine and artemisinin. Pgh-1 mainly resides within
      the parasite's food vacuolar membrane. Here, we describe a surrogate assay for
      Pgh-1 function based on the subcellular distribution of Fluo-4 acetoxymethylester
      and its free fluorochrome. We identified two distinct Fluo-4 staining phenotypes:
      preferential staining of the food vacuole versus a more diffuse staining of the
      entire parasite. Genetic, positional cloning and pharmacological data causatively
      link the food vacuolar Fluo-4 phenotype to those Pgh-1 variants that are
      associated with altered drug responses. On the basis of our data, we propose that
      Pgh-1 imports solutes, including certain antimalarial drugs, into the parasite's
      food vacuole. The implications of our findings for drug resistance mechanisms and
      testing are discussed.

PMID- 16794578
TI  - The discovery of SycO highlights a new function for type III secretion effector
      chaperones.
AB  - Bacterial injectisomes deliver effector proteins straight into the cytosol of
      eukaryotic cells (type III secretion, T3S). Many effectors are associated with a
      specific chaperone that remains inside the bacterium when the effector is
      delivered. The structure of such chaperones and the way they interact with their
      substrate is well characterized but their main function remains elusive. Here, we
      describe and characterize SycO, a new chaperone for the Yersinia effector kinase
      YopO. The chaperone-binding domain (CBD) within YopO coincides with the membrane
      localization domain (MLD) targeting YopO to the host cell membrane. The CBD/MLD
      causes intrabacterial YopO insolubility and the binding of SycO prevents this
      insolubility but not folding and activity of the kinase. Similarly, SycE masks
      the MLD of YopE and SycT covers an aggregation-prone domain of YopT, presumably
      corresponding to its MLD. Thus, SycO, SycE and most likely SycT mask, inside the
      bacterium, a domain needed for proper localization of their cognate effector in
      the host cell. We propose that covering an MLD might be an essential function of
      T3S effector chaperones.

PMID- 16794579
TI  - Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation
      of translation.
AB  - The overactivation of the HERs, a family of tyrosine kinase receptors, leads to
      the development of cancer. Although the canonical view contemplates HER receptors
      restricted to the secretory and endocytic pathways, full-length HER1, HER2 and
      HER3 have been detected in the nucleoplasm. Furthermore, limited proteolysis of
      HER4 generates nuclear C-terminal fragments (CTFs). Using cells expressing a
      panel of deletion and point mutants, here we show that HER2 CTFs are generated by
      alternative initiation of translation from methionines located near the
      transmembrane domain of the full-length molecule. In vitro and in vivo, HER2 CTFs
      are found in the cytoplasm and nucleus. Expression of HER2 CTFs to levels similar
      to those found in human tumors induces the growth of breast cancer xenografts in
      nude mice. Tumors dependent on CTFs are sensitive to inhibitors of the kinase
      activity but do not respond to therapeutic antibodies against HER2. Thus, the
      kinase domain seems necessary for the activity of HER2 CTFs and the presence of
      these HER2 fragments could account for the resistance to treatment with
      antibodies.

PMID- 16794580
TI  - Grabbing the message: structural basis of mRNA 3'UTR recognition by Hrp1.
AB  - The recognition of specific signals encoded within the 3'-untranslated region of
      the newly transcribed mRNA triggers the assembly of a multiprotein machine that
      modifies its 3'-end. Hrp1 recognises one of such signals, the so-called
      polyadenylation enhancement element (PEE), promoting the recruitment of other
      polyadenylation factors in yeast. The molecular bases of this interaction are
      revealed here by the solution structure of a complex between Hrp1 and an
      oligonucleotide mimicking the PEE. Six consecutive bases (AUAUAU) are
      specifically recognised by two RNA-binding domains arranged in tandem. Both
      protein and RNA undergo significant conformational changes upon complex formation
      with a concomitant large surface burial of RNA bases. Key aspects of RNA
      specificity can be explained by the presence of intermolecular aromatic-aromatic
      contacts and hydrogen bonds. Altogether, the Hrp1-PEE structure represents one of
      the first steps towards understanding of the assembly of the cleavage and
      polyadenylation machinery at the atomic level.

PMID- 16794581
TI  - Role of lipid trimming and CD1 groove size in cellular antigen presentation.
AB  - Cellular CD1 proteins bind lipids that differ in length (C(12-80)), including
      antigens that exceed the capacity of the CD1 groove. This could be accomplished
      by trimming lipids to a uniform length before loading or by inserting each lipid
      so that it penetrates the groove to a varying extent. New assays to detect
      antigen fragments generated within human dendritic cells showed that bacterial
      antigens remained intact, even after delivery to lysosomes, where control lipids
      were cleaved. Further, recombinant CD1b proteins could bind and present C(80)
      lipid antigens using a mechanism that did not involve cellular enzymes or lipid
      cleavage, but was regulated by pH in the physiologic range. We conclude that
      endosomal acidification acts directly, rather than through enzymatic trimming, to
      insert lipids into CD1b. Lipids are loaded in an intact form, so that they likely
      protrude through a portal near the bottom of the groove, which represents an
      escape hatch for long lipids from mycobacterial pathogens.

PMID- 16794582
TI  - Novel ferrochelatase mutations in Japanese patients with erythropoietic
      protoporphyria: high frequency of the splice site modulator IVS3-48C polymorphism
      in the Japanese population.

PMID- 16794583
TI  - Novel ALDH3A2 heterozygous mutations in a Japanese family with Sjogren-Larsson
      syndrome.

PMID- 16794584
TI  - A novel complex insertion/deletion mutation in the XPC DNA repair gene leads to
      skin cancer in an Iraqi family.

PMID- 16794585
TI  - Histamine is released following aminolevulinic acid-photodynamic therapy of human
      skin and mediates an aminolevulinic acid dose-related immediate inflammatory
      response.
AB  - Acute skin inflammation occurs following topical aminolevulinic acid-photodynamic
      therapy (ALA-PDT), but its nature and mediation are ill defined. As we observed
      an urticarial response, a potential role for histamine was explored. In 13
      healthy volunteers, we assessed the time course and dose-response of the acute
      cutaneous response(s) to ALA-PDT, the impact of H(1) antihistamine blockade, and
      measured dermal histamine release. An ALA dose series was iontophoresed into
      ventral forearm skin and exposed to red light. All participants exhibited an
      immediate urticarial response, both wheal and flare correlating with log ALA
      dose. Subsequently, a dose-related erythema developed at treatment sites by 3
      hours and persisted at 24 hours. H(1) blockade with oral cetirizine doubled the
      median minimal urticating dose of ALA and reduced the slope of dose-response for
      wheal and flare, whereas at the highest ALA dose, mean wheal and flare areas
      reduced by 68 and 60%, respectively. In contrast, cetirizine did not influence
      the 24 hour minimal phototoxic dose or erythema dose-response. Histamine release
      after ALA-PDT mirrored the urticarial response, levels peaking within 30 minutes
      and returning to baseline by 24 hours. Thus, two discrete acute inflammatory
      responses to topical ALA-PDT occur in human skin; histamine mediates the
      immediate response, but does not appear involved in the delayed phototoxicity.

PMID- 16794586
TI  - Development of intravital intermittent confocal imaging system for studying
      Langerhans cell turnover.
AB  - Although several studies have suggested relatively slow turnover of Langerhans
      cells (LCs), their actual lifespan remains elusive. Here we report the
      development of a new intravital imaging system for studying LC efflux and influx.
      Epidermal LCs expressing enhanced green fluorescent protein (EGFP) were
      visualized in anesthetized I-Abeta-EGFP knock-in mice by confocal microscopy. By
      overlaying two sets of EGFP+ LC images recorded in the same microscopic fields at
      time 0 and 24 hours later, we identified LC subpopulations that had disappeared
      from or newly emerged in the epidermis during that period. Of >10,000 LCs
      analyzed in this manner, an overwhelming majority (97.8+/-0.2%) of LCs showed no
      significant changes in the x-y locations, whereas 1.3+/-0.1% of the LCs that were
      found at time 0 became undetectable 24 hours later, representing LC efflux.
      Conversely, 0.9+/-0.1% of the LCs that were found at time 24 hours were not
      detectable at time 0, representing LC influx. From these frequencies, we
      estimated the half-life of epidermal LCs to range from 53 to 78 days, providing
      new insights into the immunobiology of LCs. Our intermittent imaging approach may
      be regarded as a technical breakthrough enabling direct visual assessment of LC
      turnover in living animals.

PMID- 16794587
TI  - Autosomal-dominant calcium ATPase disorders.
AB  - Darier disease (DD) and Hailey-Hailey disease (HHD) are the only known autosomal
      dominant Ca2+ ATPase disorders. Epidermal symptoms selectively occur in the
      affected individuals, the precise reason for which is still not fully understood.
      Here, we review the clinical, epidermal, and molecular features of the two
      genodermatoses. It is concluded that epidermal Ca2+ regulation disturbances and
      epigenetic factors may play an even more prominent role in the pathogenesis of DD
      and HHD than earlier appreciated.

PMID- 16794588
TI  - Isoform-specific regulation of the actin-organizing protein palladin during TGF
      beta1-induced myofibroblast differentiation.
AB  - Contractile myofibroblasts are responsible for remodeling of extracellular matrix
      during wound healing; however, their continued activity results in various
      fibrocontractive diseases. Conversion of fibroblasts into myofibroblasts is
      induced by transforming growth factor-beta1 (TGF-beta1) and is hallmarked by the
      neo-expression of alpha-smooth muscle actin (alpha-SMA), a commonly used
      myofibroblast marker. Moreover, myofibroblast differentiation and acquisition of
      the contractile phenotype involves functionally important alterations in the
      expression of actin-organizing proteins. We investigated whether myofibroblast
      differentiation is accompanied by changes in the expression of palladin, a
      cytoskeletal protein that controls stress fiber integrity. Palladin is expressed
      as several isoforms, including major 3Ig (90 kDa) and 4Ig (140 kDa) forms that
      differ in their N-terminal sequence. Expression of the 4Ig isoform is strongly
      induced in fibroblast stress fibers upon TGF-beta1 treatment preceding alpha-SMA
      upregulation. TGF-beta1 induced upregulation of palladin is mediated both by Smad
      and mitogen-activated protein kinase pathways. Furthermore, palladin 4Ig-isoform
      is co-expressed with alpha-SMA in vivo in experimental rat wounds and in human
      myofibroblast-containing lesions. Taken together these results identify palladin
      4Ig as a novel marker of myofibroblast conversion in vitro and in vivo. They also
      provide for the first time information about the signaling cascades involved in
      the regulation of palladin expression.

PMID- 16794601
TI  - Identification of mammalian mitochondrial proteins that interact with IAPs via N
      terminal IAP binding motifs.
AB  - Direct IAP binding protein with low pI/second mitochondrial activator of
      caspases, HtrA2/Omi and GstPT/eRF3 are mammalian proteins that bind via N
      terminal inhibitor of apoptosis protein (IAP) binding motifs (IBMs) to the
      baculoviral IAP repeat (BIR) domains of IAPs. These interactions can prevent IAPs
      from inhibiting caspases, or displace active caspases, thereby promoting cell
      death. We have identified several additional potential IAP antagonists, including
      glutamate dehydrogenase (GdH), Nipsnap 3 and 4, CLPX, leucine-rich
      pentatricopeptide repeat motif-containing protein and 3-hydroxyisobutyrate
      dehydrogenase. All are mitochondrial proteins from which N-terminal import
      sequences are removed generating N-terminal IBMs. Whereas most of these proteins
      have alanine at the N-terminal position, as observed for previously described
      antagonists, GdH has an N-terminal serine residue that is essential for X-linked
      IAP (XIAP) interaction. These newly described IAP binding proteins interact with
      XIAP mainly via BIR2, with binding eliminated or significantly reduced by a
      single point mutation (D214S) within this domain. Through this interaction, many
      are able to antagonise XIAP inhibition of caspase 3 in vitro.

PMID- 16794602
TI  - p66SHC promotes T cell apoptosis by inducing mitochondrial dysfunction and
      impaired Ca2+ homeostasis.
AB  - p66Shc, a redox enzyme that enhances reactive oxygen species (ROS) production by
      mitochondria, promotes T cell apoptosis. We have addressed the mechanisms
      regulating p66Shc-dependent apoptosis in T cells exposed to supraphysiological
      increases in [Ca2+]c. p66Shc expression resulted in profound mitochondrial
      dysfunction in response to the Ca2+ ionophore A23187, as revealed by dissipation
      of mitochondrial transmembrane potential, cytochrome c release and decreased ATP
      levels. p66Shc expression also caused a dramatic alteration in the cells' Ca2+
      handling ability, which resulted in Ca2+ overload after A23187 treatment. The
      impairment in Ca2+ homeostasis was ROS dependent and caused by defective Ca2+
      extrusion due at least in part to decreased plasma membrane ATPase (PMCA)
      expression. Both effects of p66Shc required Ca2+-dependent serine-36
      phosphorylation. The mitochondrial effects of p66Shc were potentiated by but not
      strictly dependent on the rise in [Ca2+]c. Thus, Ca2+-dependent p66Shc
      phosphorylation causes both mitochondrial dysfunction and impaired Ca2+
      homeostasis, which synergize in promoting T cell apoptosis.

PMID- 16794603
TI  - Different modes of translation for hid, grim and sickle mRNAs in Drosophila.
AB  - Protein synthesis is inhibited during apoptosis. However, the translation of many
      mRNAs still proceeds driven by internal ribosome entry sites (IRESs). Here we
      show that the 5'UTR of hid and grim mRNAs promote translation of uncapped-mRNA
      reporters in cell-free embryonic extracts and that hid and grim mRNA 5'UTRs drive
      IRES-mediated translation. The translation of capped-reporters proceeds in the
      presence of cap competitor and in extracts where cap-dependent translation is
      impaired. We show that the endogenous hid and grim mRNAs are present in polysomes
      of heat-shocked embryos, indicating that cap recognition is not required for
      translation. In contrast, sickle mRNA is translated in a cap-dependent manner in
      all these assays. Our results show that IRES-dependent initiation may play a role
      in the translation of Drosophila proapoptotic genes and suggest a variety of
      regulatory pathways.

PMID- 16794604
TI  - Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons.
AB  - Excitotoxic insults induce c-Jun N-terminal kinase (JNK) activation, which leads
      to neuronal death and contributes to many neurological conditions such as
      cerebral ischemia and neurodegenerative disorders. The action of JNK can be
      inhibited by the D-retro-inverso form of JNK inhibitor peptide (D-JNKI1), which
      totally prevents death induced by N-methyl-D-aspartate (NMDA) in vitro and
      strongly protects against different in vivo paradigms of excitotoxicity. To
      obtain optimal neuroprotection, it is imperative to elucidate the prosurvival
      action of D-JNKI1 and the death pathways that it inhibits. In cortical neuronal
      cultures, we first investigate the pathways by which NMDA induces JNK activation
      and show a rapid and selective phosphorylation of mitogen-activated protein
      kinase kinase 7 (MKK7), whereas the only other known JNK activator, mitogen
      activated protein kinase kinase 4 (MKK4), was unaffected. We then analyze the
      action of D-JNKI1 on four JNK targets containing a JNK-binding domain: MAPK
      activating death domain-containing protein/differentially expressed in normal and
      neoplastic cells (MADD/DENN), MKK7, MKK4 and JNK-interacting protein-1 (IB1/JIP
      1).

PMID- 16794605
TI  - ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3
      conversion, an essential step for autophagy formation.
AB  - Expanded polyglutamine 72 repeat (polyQ72) aggregates induce endoplasmic
      reticulum (ER) stress-mediated cell death with caspase-12 activation and
      vesicular formation (autophagy). We examined this relationship and the molecular
      mechanism of autophagy formation. Rapamycin, a stimulator of autophagy, inhibited
      the polyQ72-induced cell death with caspase-12 activation. PolyQ72, but not
      polyQ11, stimulated Atg5-Atg12-Atg16 complex-dependent microtubule-associated
      protein 1 (MAP1) light chain 3 (LC3) conversion from LC3-I to -II, which plays a
      key role in autophagy. The eucaryotic translation initiation factor 2 alpha
      (eIF2alpha) A/A mutation, a knock-in to replace a phosphorylatable Ser51 with
      Ala51, and dominant-negative PERK inhibited polyQ72-induced LC3 conversion.
      PolyQ72 as well as ER stress stimulators upregulated Atg12 mRNA and proteins via
      eIF2alpha phosphorylation. Furthermore, Atg5 deficiency as well as the eIF2alpha
      A/A mutation increased the number of cells showing polyQ72 aggregates and polyQ72
      induced caspase-12 activation. Thus, autophagy formation is a cellular defense
      mechanism against polyQ72-induced ER-stress-mediated cell death by degrading
      polyQ72 aggregates, with PERK/eIF2alpha phosphorylation being involved in polyQ72
      induced LC3 conversion.

PMID- 16794633
TI  - Nucleophosmin and cancer.
AB  - NPM1 is a crucial gene to consider in the context of the genetics and biology of
      cancer. NPM1 is frequently overexpressed, mutated, rearranged and deleted in
      human cancer. Traditionally regarded as a tumour marker and a putative proto
      oncogene, it has now also been attributed with tumour-suppressor functions.
      Therefore, NPM can contribute to oncogenesis through many mechanisms. The aim of
      this review is to analyse the role of NPM in cancer, and examine how deregulated
      NPM activity (either gain or loss of function) can contribute to tumorigenesis.

PMID- 16794634
TI  - Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer.
AB  - Transforming growth factor-beta (TGFbeta) signalling regulates cancer through
      mechanisms that function either within the tumour cell itself or through host
      tumour cell interactions. Studies of tumour-cell-autonomous TGFbeta effects show
      clearly that TGFbeta signalling has a mechanistic role in tumour suppression and
      tumour promotion. In addition, factors in the tumour microenvironment, such as
      fibroblasts, immune cells and the extracellular matrix, influence the ability of
      TGFbeta to promote or suppress carcinoma progression and metastasis. The complex
      nature of TGFbeta signalling and crosstalk in the tumour microenvironment
      presents a unique challenge, and an opportunity to develop therapeutic
      intervention strategies for targeting cancer.

PMID- 16794635
TI  - The role of nitric oxide in tumour progression.
AB  - Nitric oxide (NO) and nitric oxide synthases are ubiquitous in malignant tumours
      and are known to exert both pro- and anti-tumour effects. We summarize our
      current understanding of the role of NO in tumour progression, especially in
      relation to angiogenesis and vascular functions. We also discuss potential
      strategies for cancer treatment that modulate NO production and/or its downstream
      signalling pathways.

PMID- 16794637
TI  - Drug interactions in cancer therapy.
AB  - Drug interactions in oncology are of particular importance owing to the narrow
      therapeutic index and the inherent toxicity of anticancer agents. Interactions
      with other medications can cause small changes in the pharmacokinetics or
      pharmacodynamics of a chemotherapy agent that could significantly alter its
      efficacy or toxicity. Improvements in in vitro methods and early clinical testing
      have made the prediction of potentially clinically significant drug interactions
      possible. We outline the types of drug interaction that occur in oncology, the
      mechanisms that underlie these interactions and describe select examples.

PMID- 16794636
TI  - Photodynamic therapy and anti-tumour immunity.
AB  - Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible
      light in combination with oxygen to produce cytotoxic reactive oxygen species
      that kill malignant cells by apoptosis and/or necrosis, shut down the tumour
      microvasculature and stimulate the host immune system. In contrast to surgery,
      radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute
      inflammation, expression of heat-shock proteins, invasion and infiltration of the
      tumour by leukocytes, and might increase the presentation of tumour-derived
      antigens to T cells.

PMID- 16794638
TI  - Immunotoxin therapy of cancer.
AB  - Rationally designed anticancer agents that target cell-surface antigens or
      receptors represent a promising approach for treating cancer patients. However,
      antibodies that bind these targets are often, by themselves, non-cytotoxic. By
      attaching potent toxins we can dramatically improve the clinical utility of some
      anti-tumour antibodies. Here we describe the construction and clinical utility of
      several recombinant immunotoxins; each of which is composed of antibody Fv
      fragments fused to powerful bacterial toxins. Results from clinical trials
      indicate that recombinant immunotoxins and similar agents that are designed to
      combine antibody selectivity with toxin cell-killing potency will be useful
      additions to cancer therapy.

PMID- 16794639
TI  - The US Food and Drug Administration perspective on cancer biomarker development.
AB  - Despite the intense interest in biomarker development for cancer management, few
      biomarker assays for diagnostic uses have been submitted to the US Food and Drug
      Administration (FDA). What challenges must researchers overcome to bring cancer
      detection technologies to the market and, therefore, into clinical use?

PMID- 16794640
TI  - Intercurrent medical diseases: incidence and effects on the course of anaesthesia
      in a tertiary hospital.
AB  - AIM: A prospective study was carried out to determine the incidence of
      intercurrent medical diseases and peri-operative course of such patients
      presenting for surgery under anaesthesia at the University of Benin Teaching
      Hospital, Benin City, for a period of twelve months.(March 2002 - February 2003).
      PATIENTS AND METHODS: All patients presenting for surgery at our general modular
      operating rooms formed the subjects for this study. A standardized form was used
      to document patients characteristics, presence of medical diseases, level of
      control, indication for surgery, type of anaesthesia, perioperative complications
      and outcome. RESULTS: Five hundred patients had surgery under anaesthesia. Our
      data showed incidence of intercurrent medical diseases (IMD) to be 19.6% . The
      prevalent age of intercurrent medical diseases was 60 years and above. The
      incidence of common illnesses was: hypertension (41.86% ), diabetes (14.2% ),
      upper respiratory tract infection (11.22% ), obesity (9% ) and anaemia (6.1% ).
      The most frequent observed intraoperative complications in patients with IMD were
      cardiovascular (hypertension-19.04% , bradycardia-19.04% , hypotension- 14.29%
      and tachycardia-14.29% . In recovery room, the common documented complications
      were hypertension-30% , tachycardia-22.5% , hypotension- 12.5% and prolonged
      unconsciousness-10% . The incidence of perioperative adverse events was higher in
      patients with IMD than in those without IMD. It was extremely significant.
      (P=0.0006; Odds ratio=0.5115; 95% CI: 0.3510 - 0.7455 using the approximation of
      Woolf). Patients aged over 60 years were more likely to present for surgical
      treatment with intercurrent medical conditions. (p < 0.0001, Odds ratio=0.03843,
      95% CI: 0.2141 - 0.06900). CONCLUSION: Intercurrent medical disease was commonly
      found in patients above 60years and is a predictor of both intraoperative and
      postoperative adverse events.

PMID- 16794641
TI  - Effect of cervical traction on cardiovascular and selected ECG variables of
      cervical spondylosis patients using various weights.
AB  - BACKGROUND: There is currently no consensus among the clinicians regarding the
      tractive force to be employed during cervical traction (CT) that will correlate
      precisely with the percentage body weight of the patient and reduce the side
      effects associated with CT therapy. OBJECTIVE: This study therefore aimed to
      investigate the response of cervical spondylosis (CS) patients to different CT
      weights and to establish the effect of CT on the cardiovascular system of
      patients with cervical spondylosis (CS). METHODS: Sixty out of 78 subjects
      participated in the study. They were randomly assigned into three experimental
      groups A, B and C. Their systolic and diastolic blood pressures (SBP and DBP) and
      heart rates (HR) were measured. Rate pressure product (RPP) was calculated using
      standard equation18 and ECG recorded using the KENZ, 201 machine. Subjects'
      cardiovascular and ECG responses were monitored in a supine resting position
      (baseline) and under three experimental conditions using the subjects' 7.5% kg
      total body weights (TBW), 10% kg TBW and 15% TBW at different time intervals (5,
      10 and 15 minutes respectively). RESULTS: Compared with the baseline values,
      there was a drop in SBP, DBP and RPP for all subjects in the three groups. The
      SBP, DBP and RPP alteration were not significant for the 7.5% TBW CT, but
      significant (p <0.05) for the 10% and 15% TBW tractions. The HR and ECG variables
      revealed no significant difference in all the groups, these results signified
      that the cardiac muscles were not adversely affected by any of the traction
      weights during application. Twenty subjects had side-effects including 5 subjects
      that terminated the treatment due to pain during the CT application. CONCLUSIONS:
      Cardiovascular alterations do occur during the application of cervical traction
      weights resulting in untoward patient's reactions. Efforts should be made to
      monitor the cardiovascular variables during and immediately after CT especially
      in "high risk" patients, that is, elderly patients and patients with unstable
      cardiovascular systems.

PMID- 16794642
TI  - Rampant caries experience in a Nigerian teaching hospital population.
AB  - OBJECTIVES: A prospective study to find out the prevalence, pattern of
      distribution of rampant caries in patients treated at the outpatient clinic of
      the Dental Hospital, Obafemi Awolowo University Teaching Hospital Complex (
      OAUTHC) Ile - Ife, Nigeria. METHOD: A total of 403 child patients aged 1 to 5
      years who attended the hospital from January 1998 to December 2002 were examined
      by the authors. Questionaires were given to the parents or guardians to complete.
      RESULTS: The sample consisted of 213 males (52.8% ) and 190 females (47.2% ).
      Twenty two children (15males, 7 females) presented with rampant caries which was
      not statistically significant P >0.5. The prevalence of rampant caries was 5.5% .
      The peak age incidence was 4 years. More boys suffered rampant caries than girls
      with boy to girl ratio of 2:1. The pattern of distribution showed that the labial
      surfaces of the maxillary incisors were affected in all the patients. Five
      patients had proximal caries out of which mandibular primary incisors of 3
      children were involved and one child presented with palatal caries of the
      maxillary primary incisors. CONCLUSION: The Dental Hospital, OAUTHC has
      experienced increased in number of rampant caries patients. Therefore emphasis on
      prevention of caries in suburban Nigerian children in Ile-Ife should be stepped
      up before it constitutes a significant oral health problem.

PMID- 16794643
TI  - Serum fructosamine in the assessment of glycaemic status in patients with sickle
      cell anaemia.
AB  - AIM: To assess the usefulness of fructosamine in evaluating the glycaemic status
      in patients with sickle cell anaemia. METHOD: Serum fructosamine, glucose,
      albumin and bilirubin were measured in one hundred and fifty patients with sickle
      cell anaemia (HbSS), fifty poorly controlled diabetics and one hundred healthy
      control subjects. Fructosamine was assayed using the method of Johnson et al.
      RESULTS: None of the HbSS patients had hyperglycaemia. Serum fructosamine was
      significantly higher in the poorly controlled Diabetics compared to the HbSS
      patients and the Controls. The mean serum albumin levels were within the
      laboratory's reference interval in the three groups of subjects studied. There
      was no significant correlation between fructosamine and normal serum albumin in
      the three groups of subjects. Moderately raised serum bilirubin concentrations in
      the HbSS patients did not cause any significant interference in the assay of
      fructosamine in the patients. CONCLUSION: Serum fructosamine could be reliably
      employed as a measure of glycaemic status of patients with sickle cell anaemia
      with moderate hyperbilirubinaemia.

PMID- 16794644
TI  - Pattern of biochemistry laboratory requests and results in north eastern Nigeria.
AB  - OBJECTIVES: Deficient action of insulin is associated with derangement of
      carbohydrate, fat and protein metabolism. Determination of the extent of such
      derangement in steady state type 2 diabetic patients enhances management planning
      and prevents diabetic complications. This is necessary in a poor resource setting
      where functional national health insurance scheme is not available. The study
      aimed at assessing the level of plasma glucose and lipids, renal function, total
      calcium, inorganic phosphates and albumin and their relevance in steady state
      type 2 diabetic patients in north-eastern Nigeria in order to minimize the cost
      of laboratory investigations while preventing diabetic complications. METHOD: Two
      hundred and eighteen steady state type 2-diabetic patients were recruited at the
      Chemical pathology laboratory of the University of Maiduguri Teaching Hospital
      over a period of one year. Tests requested by the Clinicians for steady state
      diabetics were collated, the pattern of biochemistry laboratory requests and
      results were determined. The mean and standard deviation of the results were
      calculated. RESULTS: Out of the 218 steady state diabetics, only 48 (22.2 % ) had
      good short-term glycaemic control (fasting blood glucose < 7mmol/l). No test for
      long-term glycaemic control was requested during the study period. Lipid profile
      and protein assessment were carried out in 30% and 52.3 % of the patients
      respectively. Biochemical tests were not optimally utilised and this resulted in
      poor glycaemic control. CONCLUSION: Proper utilisation of laboratory tests for
      adequate long-term glycaemic control through team work approach with laboratory
      physicians are recommended.

PMID- 16794645
TI  - Seroprevalence of hepatitis C virus in the Niger Delta of Nigeria.
AB  - The objective of this cross-sectional survey was to determine the prevalence of
      anti bodies to hepatitis C virus in 366 consecutively recruited individuals
      comprising 209 males and 157 females. Anti-HCV was detected in 11 (3.0% ) of the
      subjects tested. The highest prevalence was found in the 30-39 year age group
      (3.8% ) while the lowest prevalence occurred in the 40-49 year group (2.2% ).
      Anti-HCV infection prevalence was higher in less educated subjects (4.6% )
      compared to highly educated (1.4% ), in females (3.8% ) compared to males (2.4% )
      and was found to be almost two times higher among unmarried (4.1% ) compared to
      married subjects (2.2% ). This study confirms a high prevalence of anti-HCV and
      calls for urgent health education and awareness in the Niger Delta area of
      Nigeria to check further spread of the virus.

PMID- 16794646
TI  - HIV/AIDS in Ilorin: changing trend, emerging risk factors.
AB  - OBJECTIVE: We examined HIV seropositivity rates among blood donors, subjects
      screened for certificate purposes, and four sentinel surveys. Demographic and
      clinical features were analysed over periods to determine changes in risk factors
      and groups at risks. METHODOLOGY: Questionnaires and protocols were completed for
      patients screening or clinically assessed, while HIV positivity was determined on
      the basis of reactivity with two different ELIZA techniques. RESULTS: The
      positivity rates were below 2% in blood donors, maximum of 4.3% for sentinel
      surveys, and 11% among subjects screened for certificate purposes. Results showed
      decreasing male:female ratio, younger female patients, and preponderance of
      traders and artisans. Weight loss, fever, and diarrhoea were the commonest
      presenting features. 41% live away from their spouses. CONCLUSION: The 11%
      positivity rate among subjects requiring certificates raises questions on the
      reliability of sentinel survey figures. Campaigns should be targeted at artisans,
      traders and those living away from their spouses.

PMID- 16794647
TI  - Religious leaders' perceptions and support of reproductive health of young people
      in Anambra State, Nigeria.
AB  - OBJECTIVES: This article assesses religious leaders' perceptions of young
      people's reproductive health in Anambra State. PATIENTS AND METHODS: Through self
      administered semi-structured questionnaires, and in depth interviews, religious
      leaders perceptions of young peoples reproductive health in Anambra State Nigeria
      was elicited from two hundred and fifty religious leaders selected by multistage
      random sampling. RESULTS: Over 85% of the religious leaders thought that young
      people are sexually active, and are involved in high risk behaviour for
      unintended pregnancy, unsafe abortion, and STD and HIV/AIDS. Eighty five per cent
      felt that there is need for sexuality education in schools, and that sexuality
      education will reduce unintended pregnancy, abortion, STDS and HIV/AIDS among
      young people. However 52.2% felt that sexuality education in school would
      increase promiscuity. Some religious leaders did not support teaching of
      contraception and safe abortion in schools. CONCLUSION: Religious leaders in
      Anambra State have a high awareness of young people's reproductive health
      problem, and are in support of sexuality education in schools. They differ
      however in what should be the content of the curriculum. There is need to
      harmonise and agree on programme contents to minimise sending conflicting and
      confusing messages to young people.

PMID- 16794648
TI  - Perceptions and practices of private medical practitioners to adolescent
      reproductive health in Lagos State, Nigeria.
AB  - INTRODUCTION AND OBJECTIVES: Adolescent sexual and reproductive ill health is a
      major global public health issue, contributing to high levels of morbidity and
      mortality in adolescents. Although adolescents are known to have low levels of
      doctor consultations, private medical practitioners remain the preferred health
      care providers. This study was carried out to document the attitudes and
      experiences of private medical practitioners to adolescent reproductive health
      issues and to assess the factors that may influence their attitudes. METHODS:
      Information was obtained from a random sample of 187 out of 352 (53% ) registered
      private medical practitioners in 5 of the 20 Local Government Areas in Lagos
      State using a self-administered structured questionnaire. RESULTS: Sixty-two per
      cent of the doctors claimed they saw adolescents regularly, mainly for the
      treatment of sexually transmitted infections (STIs). Many (86% ) believed that
      adolescents should use contraception and suggested that parents, teachers and
      health workers provide sexuality information to adolescents. Sixty one percent of
      the practitioners believed that abortion should be legalised, though with
      restrictions. Many of them admitted to providing post abortion care to
      adolescents. The religious affiliation of the private medical practitioners
      influenced their perception and practices. CONCLUSION AND RECOMMENDATIONS:
      Improving the reproductive health care of adolescents is key to improving the
      world's future economic and social well being. It is recommended that appropriate
      sexuality education be made widely available to adolescents. In addition, private
      medical practitioners should strengthen their skills and be more actively
      involved in the care of adolescents by making their facilities more adolescent
      friendly.

PMID- 16794649
TI  - Role of computed tomography in the management of adult brain tumours.
AB  - BACKGROUND: Neuroradiologic imaging has revolutionised the management of brain
      tumours through precise presurgery diagnosis and accurate definition of the
      extent of disease. This report attempts to evaluate our five years of clinical
      experience with intracranial CT scanning in the management of adult brain
      tumours. MATERIALS AND METHODS: The study included 160 adults with demonstrable
      brain tumours on CT imaging between 1997 and 2001. Surgical confirmation and
      histologic typings were recorded. All CT scans were carried out on Siemens
      Somatom AR.T scanner. A complete CT examination includes pre- and post-contrast
      examination done at 5 to 10 mm slice thickness and 10 mm interval from the base
      of skull to the vertex. All scans were viewed and documented in soft tissue and
      bone windows and multiplanar reconstruction appropriate for optimum visualisation
      of the areas of interest. All CT scans of the study population were analysed by
      age, sex, symptomatology, type and location of tumour. RESULTS: There were 92
      males and 68 females with a mean age of 48 +/- 0.68 years. Headache accounted for
      41.2% of the presenting symptoms while cerebral hemispheric tumours are more
      frequently (60.6% ) encountered. Gliomas are the commonest group (68.8% ).
      CONCLUSION: CT examination has improved the management of patients with brain
      tumours in our teaching hospital and will continue to remain the mainstream
      neuroradiologic imaging technique for a very long time.

PMID- 16794650
TI  - Rabies in apparently healthy dogs: histological and immunohistochemical studies.
AB  - A slaughterhouse survey for rabies virus infection among apparently healthy dogs
      slaughtered for human consumption was carried out in Maiduguri, Nigeria. Formalin
      fixed and paraffin-embedded tissues (salivary gland, hippocampus, cerebrum,
      medulla, and trigeminal ganglion) were obtained from a total of 52 head samples
      from slaughtered dogs. The paraffin-embedded tissues were analysed histologically
      using the haematoxylin and eosin (H&E) method for the presence of inclusion
      bodies and histochemically by streptavidin - biotin peroxidase staining method
      for detection of rabies virus antigens. Prior to fixation of tissue, impression
      smears were made from the hippocampus and stained by Sellers method to detect the
      presence of Negri bodies. Rabies virus antigen was detected in tissues from 16
      (31% ) of the 52 dog heads. Histological diagnosis by H&E revealed various
      degrees of inflammatory changes in the salivary gland and brain tissues with few
      Negri bodies from 10 (19% ) of the 52 dogs tested. However, all tissues positive
      by H&E were also positive by immunoperoxidase method using the streptavidin-
      biotin peroxidase staining procedure. Ten (30% ) of the 33 male and 6 (32% ) of
      the 19 female dogs tested were positive for presence of rabies virus antigen.
      There was no significant difference between sexes in relation to rabies virus
      infection. The application of immunoperoxidase staining technique in the
      localization of rabies virus antigen in the submaxillary salivary gland was more
      sensitive (based on the relative number of positive tissues) when compared with
      the application of the method to other organs. Apparently healthy dogs may be
      important in the epidemiology and control of rabies in this environment.

PMID- 16794651
TI  - Removal of selected fracture fixation implants under local anaesthesia.
AB  - AIMS AND OBJECTIVES: This study was undertaken to evaluate the feasibility and
      tolerability of fracture fixation implants (FFI) removal under local anaesthesia.
      MATERIALS AND METHODS: We reviewed 176 patients who had osteosynthetic materials
      inserted for the treatment of fractures and whose implants were removed under
      local anaesthesia. Pain and tolerance were determined using a pain severity score
      determined by the patients. About 60% of the implants were Kuntcher nails while
      31% were Krischner wires. In 171 (97.2% ) patients the implants were removed
      under local anaesthesia while in 5 (2.8% ) patients with Kuntcher nails the
      procedures were difficult and painful which necessitated the use of intravenous
      ketamine. RESULTS: About 89% of patients felt no pain during the procedures while
      8.5% felt mild to moderate pain, which was easily tolerated. CONCLUSION: The use
      of local anaesthesia for fracture fixation implants removal is recommended
      because it is simple and safe and reduced the cost and complications of
      treatment.

PMID- 16794652
TI  - HIV seroprevalence in Nigerian patients with surgical lesions of the brain:
      implications for management.
AB  - BACKGROUND AND OBJECTIVE: This study was done to estimate the seroprevalence rate
      among Nigerian patients presenting to hospital with neurosurgical disease.
      PATIENTS AND METHOD: We reviewed our patients' hospital records from October 1996
      to October 2001 for clinical presentation and diagnosis, cranial CT findings,
      results of retrovirus screening and mode of management. RESULTS: Sixteen (10
      males and 6 females) out of 601 patients screened for HIV by ELISA were confirmed
      by Western Blot to be positive, giving a seroprevalence rate of 2.7% . Twelve of
      the HIV-positive patients were asymptomatic for HIV disease. CONCLUSION: There is
      a low but definite risk of HIV transmission to health workers managing patients
      with surgical lesions of the brain in areas where HIV is prevalent. Asymptomatic
      seropositive HIV patients with surgically curable intracranial disease should be
      managed with the most minimally invasive procedure appropriate for the surgical
      lesion under universal protective measures.

PMID- 16794653
TI  - Functional cast bracing in the management of open forearm fractures: a
      preliminary report.
AB  - BACKGROUND: Management of any injury is expensive to the individual and the
      community. For this reason modification of methods of managing trauma very often
      is necessary in resource poor countries. OBJECTIVE: To verify the effectiveness
      of metal hinge joints in prevention of contractures and ankylosis of the elbow
      joint in cast immobilisation of reduced open forearm fractures. PATIENTS: 20
      patients who had sideswipe injuries were managed from the year 01/01/2000 to date
      (20/5/2004) by the orthopaedic unit of Usmanu Danfodiyo University Teaching
      Hospital, Sokoto, Nigeria. They were referred from General Hospitals and
      Rural/Primary Health centers in northwestern Nigeria. They were all males,
      between the third and fourth decades of life (mean age was 35.54+1.52years).
      METHODS: Management of these patients involved early anti tetanus prophylaxis,
      good wound hygiene, internal fixation of the reduced fractures with kirschner
      wires, cast immobilisation and incorporation of metal hinge joints at the elbow
      joint. Three days after surgery the casts were windowed and patients were
      discharged to continue wound dressing at the nearest Health Centres. The metal
      hinge joints permitted elbow joint movement throughout the period of
      immobilization. After 12.45+0.42 weeks (mean length of time of wound healing in
      these cases) casts and implants were removed. RESULTS: Active movement of the
      elbows was rated as very good (8 cases), good (6 cases) and fair (6 cases). Plain
      radiography of the forearms showed fifteen cases of union and five cases of
      nonunion of fractures. CONCLUSIONS: The outcome of treatment of these injuries
      discerns the effectiveness of functional cast bracing in the prevention of
      contractures and ankylosis of the elbow joint in cast immobilization of reduced
      open forearm fractures. The healed wounds made the skin safer for further
      management of the cases of nonunion.

PMID- 16794654
TI  - Ultrasound as a diagnostic aid in head and neck lesions.
AB  - AIM: This article reviewed the diagnostic values of ultrasound in head and neck
      lesions with a view to emphasising its importance to Maxillo-Facial Surgeons in
      Nigeria. MATERIALS AND METHODS: A computerised literature search using MEDLINE
      was conducted for publications on ultrasonography in head and neck region. Mesh
      phrases used in the search were: ultrasound and head and neck; ultrasound and
      oral lesions. RESULTS: Ultrasound has been found to be a reliable and sensitive
      diagnostic tool in the diagnosis of soft tissue cysts, vascular neoplasms, deep
      neck abscesses, palatal tumours, salivary gland diseases, fractures of facial
      bone, solid and cystic lesions of the jaws, temporomandibular joint pathology,
      head and neck cancer and nodal metastases. Its sensitivity and specificity for
      some lesions have been found to be comparable to those of computerised tomography
      and magnetic resonance imaging. CONCLUSIONS: Ultrasound is an established
      valuable diagnostic tool for head and neck lesions. The success of
      ultrasonography is highly dependent on the frequency of the probe, the higher the
      resolution the better the accuracy. Its advantages include being non-invasive,
      without any known deleterious biological effect, rapid, painless, inexpensive and
      easily reproducible.

PMID- 16794655
TI  - An audit of surgical admissions to the intensive care unit of the Lagos
      University Teaching Hospital (1997 - 2002).
AB  - OBJECTIVE: To review the pattern of adult surgical admissions into the Intensive
      Care Unit (ICU) of Lagos University Teaching Hospital (LUTH). METHODS: A six-year
      retrospective review of data of patients above 12 years old admitted to the ICU
      of LUTH was performed. RESULTS: 290 patients representing 82.6% of the total ICU
      admissions (351) during the study period were evaluated. 251 (86.6% ) were
      surgical and 39 (13.4% ) non-surgical. The overall mortality was 40.3% (Surgical 
      37.8% , Medical 62.9% ). Emergency admissions accounted for 221 (76.2% ) while
      electives were 69(33.8% ). The Mean hospital stay (MHS) was 4.8 +/- 0.4 days
      (Surgical: Medical - 3.9 +/- 0.2:10.1 +/- 2.5). The highest admissions were as a
      result of trauma (32.1% ) and obstetric complications (9.7% ). Cardiorespiratory
      monitoring (57.2% ) and respiratory distress (34.1% ) were the main indications
      for admission. Emergency admission and artificial ventilation contributed
      significantly to the observed mortality (p < 0.0001) CONCLUSION: At LUTH, trauma
      and obstetric complications constituted the major causes for ICU adult surgical
      admissions.

PMID- 16794656
TI  - Stroke in young adults: report of three cases and review of literature.
AB  - OBJECTIVE: To highlight the occurrence, and review the literature on stroke in
      young adults. METHODS: This paper reports three cases of young strokes. Brain
      imaging was done for two cases. The two were haemorrhagic stroke; one from an
      identified arteriovenous malformation and the other from a suspected vascular
      malformation or intracranial aneurysm. The third case was a young man with
      nephrotic syndrome who presented with clinical features of a thrombotic stroke. A
      review of the literature on stroke in young adults was done via Medline search
      for relevant publications. RESULTS: The literature review shows that a thorough
      diagnostic work up is required in young adults with stroke if one is to identify
      the diverse, but often treatable, causes of stroke in this age group. CONCLUSION:
      Stroke is a significant, albeit uncommon, cause of mortality and morbidity in
      young adults.

PMID- 16794657
TI  - Ileosigmoid knotting in a young adult in Enugu, Nigeria - a case report.
AB  - A 25-year old male student who was seen in the emergency unit of our hospital
      with symptoms and signs of acute intestinal obstruction of 4 days duration is
      presented. Following resuscitation, an exploratory laparotomy revealed a long
      gangrenous jejunoileal segment with its base firmly knotted around the mesentery
      of the sigmoid colon which was also gangrenous. Resection and primary anastomosis
      of the small bowel was carried out. Hartmann's colostomy was also done following
      resection of the sigmoid colon. The features of this uncommon presentation of
      intestinal obstruction described in the literature as ileosigmoid knotting or
      compound volvolus are highlighted, with particular note that its recognition,
      rapid resuscitation and exploration will improve prognosis.

PMID- 16794658
TI  - Spontaneous heterotropic pregnancy in sickle cell disease with survival of the
      abdominal pregnancy.
AB  - A case is presented of a spontaneously conceived heterotopic pregnancy in a 38
      year-old Haemoglobin SS woman, with intrauterine foetal demise and survival of
      the extra-uterine pregnancy, which was an abdominal pregnancy. The diagnosis was
      not made until delivery. This report should create the awareness of the
      possibility of abdominal or heterotopic pregnancy in spontaneous cycles,
      particularly in patients with recurrent severe anaemia in pregnancy, whether or
      not they have haemoglobinopathies.

PMID- 16794659
TI  - High tension electricity burns: a case report.
AB  - BACKGROUND: Recently in some areas there has been an upsurge in rural
      electrification. Though electricity is desirable, it is one of the most
      potentially dangerous commodities in the society. OBJECTIVE: We present this
      report highlighting the need for prevention as high tension electricity injury
      though uncommon is reputed for significant morbidity and mortality. METHOD: A
      case report of a 30 year old female trader with high tension electricity burns in
      a rural community seen in the University of Calabar Teaching Hospital, Calabar.
      RESULT: Successful management of 10% burn involving multiple sites. Patient's
      husband was electrocuted in the incident. CONCLUSION: High tension burns are
      reputed for significant morbidity and mortality hence the need for prevention.
      Strategies recommended should include safety of electrical installations,
      protective apparels for electricity workers as well as health education for
      consumers.

PMID- 16794660
TI  - [Counting abortions].

PMID- 16794661
TI  - [Use of electroconvulsive therapy].

PMID- 16794662
TI  - [Bridges instead of hostility].

PMID- 16794663
TI  - [Profession as a risk factor of disease].

PMID- 16794664
TI  - [Paracetamol poisoning--occurrence and treatment].
AB  - BACKGROUND: Poisoning with paracetamol is common and potentially serious. We have
      assessed the incidence of paracetamol poisoning and the hospital's use of serum
      analyses to monitor the antidotal treatment N-acetyl cysteine. MATERIAL AND
      METHODS: All hospital records of ICD-10 diagnoses T4n and T50.9 at the Department
      of Acute Medicine from July 2001 to July 2004, were retrospectively reviewed. All
      cases with possible or confirmed paracetamol poisoning were recorded. Liver
      damage was defined as ALT above 1,000 U/l. Standard European treatment nomogram
      was used. RESULTS: Of 869 admissions with acute poisoning, 158 (21%) were caused
      by paracetamol; of these 120 (76%) were women and 38 (24%) were men. 107 (68%) of
      the patients were treated with N-acetyl cysteine at admission due to suspected
      ingestion of more than 10 grams of paracetamol. Treatment was abrupted in 84
      (79%) of the patients, as levels of serum paracetamol were below the treatment
      line in the nomogram. The median time from admission to sampling was 5 hours.
      Nine patients (6%), who all arrived later than 15 hours after ingesting
      paracetamol, developed liver damage. One woman died after a sub-acute overdose of
      paracetamol. INTERPRETATION: Few patients needed treatment with antidote. The
      treatment seemed to protect all against liver damage if started early. Liver
      damage and death was associated with admission later than 15 hours after intake.

PMID- 16794665
TI  - [Abortion among young women--the importance of family environment factors and
      social class].
AB  - BACKGROUND: The aim of the study was to investigate possible associations between
      social background, other aspects of childhood environment and induced abortion
      among young women. MATERIAL AND METHODS: Norwegian girls (N = 2,198), comprising
      a representative sample, were followed up through three data collections from
      they were in their teens in 1992 till they were young adult women (20 - 27 years)
      seven years later. A questionnaire was used to collect the data and the analyses
      were conducted by Cox regression. The response rate for the first data collection
      was 97%. The cumulative response rate over all three data collections was 69 %.
      RESULTS: In young adulthood we uncovered a steady reduction of induced abortion
      rates with increasing educational level. Women who had grown up in Northern
      Norway had higher rates than other women. There was a lower risk for induced
      abortion when parents were well educated and had fairly good jobs. Further, there
      were associations to parental divorce, weak parental monitoring and parental
      alcohol abuse. INTERPRETATION: A host of socioeconomic factors are associated
      with abortion risk. We need more thorough knowledge about these factors. We can,
      however, conclude that preventive efforts in this area should be targeted towards
      groups with risk factors.

PMID- 16794666
TI  - [Self-decided abortion--different interpretations of 12 weeks of gestation].
AB  - BACKGROUND: By the end of 12 gestational weeks, Norwegian women may decide on
      their own if they want to terminate their pregnancy. According to the abortion
      law, the upper gestational age is defined as 12 completed weeks or 84 days
      calculated from the first day of the last menstrual period (LMP). Using
      ultrasound, the recommended upper limit of the crown rump length (CRL) is 66 mm
      and the outer-to-outer biparietal diameter 26 mm. METHOD: In a questionnaire
      survey we asked how Norwegian hospital departments that offer pregnancy
      termination define 12 completed weeks and the upper limit of the CRL, and what
      method they use in case of a discrepancy in gestational length between LMP and
      ultrasound. RESULTS: All but one of the 46 hospitals we addressed nationwide
      completed the questionnaire (97.8%). More than half had a wider definition of 12
      gestational weeks than the law, the upper limit for CRL varied between 50 and 73
      mm, while all used ultrasound in case of a discrepancy. INTERPRETATION: Even if
      clinical practice varies between hospitals, most of them interpret gestational
      age liberally. Women with the same length of gestation around 12 weeks, may be
      managed differently depending on where they are referred for a pregnancy
      termination.

PMID- 16794667
TI  - [Electronic prescriptions--without side-effects?].
AB  - BACKGROUND: In a government document published in 2005, electronic information
      systems were held up as important tools for reducing unintended adverse drug
      events. The Norwegian Social and Health Directorate has now initiated a large
      national project introducing electronic prescribing. MATERIAL AND METHODS: We
      have analysed recent international literature about electronic prescribing and
      computerised physician order entry. RESULTS: Electronic information systems may
      cause both a reduction and an increase in adverse drug events. Certain known
      errors disappear, but new risks for errors are introduced. A new system might
      change or unintentionally put aside well-established safety routines in manual
      systems of today. INTERPRETATION: Introduction of electronic treatment of drug
      information can give many benefits, but if the risks for introducing new errors
      are underestimated, patient safety might be threatened. A strategy for avoiding
      possible mistakes should therefore be developed simultaneously with introduction
      of systems for electronic prescribing and order entry. New systems have to be
      thoroughly tested and evaluated as closely as other new technology and drugs when
      implemented.

PMID- 16794668
TI  - [Requested abortions in Oslo 2000-2003].
AB  - BACKGROUND: Women of non-Western origin are over-represented among women
      requesting induced abortion before the end of the 12th week of pregnancy, in
      Oslo, Norway. Our aim was to find out if that was also the case for women
      requesting induced abortion after week 12. MATERIAL AND METHODS: We assessed
      differences between Western and non-Western women in duration of pregnancy at
      request for induced abortion and the proportion accepted for abortion. All women
      requesting induced abortion after the 12th week of pregnancy at Ulleval
      University Hospital, Oslo from January 2000 to September 2003 (n = 378) were
      included. Information about the number of fertile women in Oslo according to
      ethnic background was found in the municipality of Oslo's statistical office.
      Other data were obtained from patient medical records. RESULTS: 23% (87/378) of
      all women requesting late induced abortion and 15.5% (20,636/132,843) of women
      aged 15-50 years in Oslo had non-Western background (p < 0.05). The mean
      gestational age at the time of requested abortion among non-Western women was
      16.4 weeks and among Western women it was 15.6 weeks (p = 0.01). There was a non
      significant increased risk of having the abortion request rejected for non
      Western as compared to Western women (adjusted odds ratio 1.6; 95% CI 0.5-5.5),
      after control for gestational age and maternal age. INTERPRETATION: It is known
      that non-Western women in Oslo are over-represented among women giving birth and
      women requesting induced abortion in general. This study shows that non-western
      women are also over-represented among women requesting induced abortion after the
      12th pregnancy week.

PMID- 16794669
TI  - [The Mother and Child Cohort Study will give new answers].
AB  - Most severe diseases cannot be prevented. The main reason is lack of information
      about their causes. The Norwegian Mother and Child Cohort Study (MoBa) is a
      population-based cohort with 100,000 children included from fetal life. The
      ambitious goal is to understand the causal chains behind diseases and the
      comprehensive data collection will allow many diseases to be addressed. The
      overall goal is to come up with good preventive measures. The purpose of this
      article is to inform about MoBa and to stimulate enhanced use of data collected
      during research.

PMID- 16794670
TI  - [Electroconvulsive therapy in the Ullevaal region of Oslo 1988-2002].
AB  - BACKGROUND: Electroconvulsive treatment (ECT) has been used less frequently in
      Norway than in Denmark and Sweden. The aim of this investigation was to study the
      use of ECT in female and male patients in different age-groups in the Ullevaal
      region of Oslo from 1988 to 2002, and to compare the results with studies in
      Denmark and Sweden. METHOD: The protocols of ECT treatments in three clinical
      departments serving the Ullevaal region and relevant population data were used to
      calculate the annual number of ECT courses per age- and gender-specified
      population groups of 100,000. RESULTS: Use of ECT increased progressively from
      2.3 to about 20 patients per 100,000 per year (p < 0.001). In the late 90s the
      increased use of ECT approached the use in Denmark and Stockholm. From 1988-92 to
      1993-97 the use of ECT increased significantly in all age groups in women and men
      above 70 years. From 1993-97 to 1998-2002 the increase was significant in women
      and men above 70 years. From 1998 to 2002 the annual rates of ECT increased with
      increasing age for both sexes. In women aged > or = 70 years the rate of ECT was
      only 1.5 times higher than in men. INTERPRETATION: The study confirms increased
      use of ECT in the Ullevaal region after 1988. The use of ECT in this region
      approached the decreased use in Denmark and Stockholm. The increased use occurred
      particularly in patients above 70 years.

PMID- 16794671
TI  - [Prescription changes in pharmacies].
AB  - BACKGROUND: Prescriptions must sometimes be changed or clarified before
      dispensing in order to provide a safe and professional service. The aims of this
      study were to gain insight into the types of prescription interventions performed
      by pharmacists, to explore the reason behind the interventions and to describe to
      which extent and how interventions are documented and communicated to the
      prescribers. MATERIAL AND METHODS: Prescription interventions (N = 1,084)
      performed at a community pharmacy in Norway from January 2002 to September 2004
      were categorised. Two focus groups were used to validate the categories. The
      pharmacists in these groups were invited to discuss working procedures and
      professional judgements related to prescription interventions. RESULTS: The
      prescription interventions were grouped into seven categories. The two largest
      categories were "drugs not available" (37%) and "clarification of drug choice and
      dosage" (22%). Many interventions are not communicated to the prescribers. In
      principal, the pharmacists felt that interventions should be communicated to the
      prescriber even if this is often not the case. CONCLUSION: Pharmacists intervene
      on a range of prescription issues that are not communicated to the prescribers.
      Feedback requires time and resources for all involved. By ensuring that computer
      systems used by general practitioners comply with reimbursement legislation and
      technical requirements for prescriptions, the demand for many prescription
      interventions will be reduced. There is a need for a joint professional
      discussion on differentiation and standardisation of feedback on prescription
      interventions.

PMID- 16794672
TI  - [Reimbursement prescription system in poor state?].

PMID- 16794673
TI  - [Physician's role--between medicine and patient flow].

PMID- 16794674
TI  - [Small patients--big challenges].

PMID- 16794675
TI  - [Catheter-directed thrombolysis in acute deep venous thrombosis].

PMID- 16794676
TI  - [Politics and science in colorectal cancer screening].

PMID- 16794677
TI  - [Unscientific article about biological rhythms and depression].

PMID- 16794679
TI  - [A wonder about Tidsskriftet's prioritization].

PMID- 16794691
TI  - Invariance and noninvariance of the spectra of stochastic electromagnetic beams
      on propogation.
AB  - It has been known for some time that the spectrum of light may change on
      propagation, even in free space. The theory of this phenomenon was developed
      within the framework of scalar theory. We generalize it to electromagnetic beams,
      generated by planar, secondary, stochastic sources. We also derive an
      electromagnetic analog of the so-called scaling law. When this law is satisfied
      the normalized spectrum of the beam is the same throughout the far zone and
      across the source.

PMID- 16794692
TI  - Water-soluble porphyrin detection in a pure-silica photonic crystal fiber.
AB  - Aqueous solutions of the water-soluble porphyrin 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphyrinatomanganese(III) acetate were inserted into the holes
      of a photonic crystal fiber, and the porphyrin absorption bands were identified.
      Results were obtained for three concentrations. The porphyrins in water show no
      surface interactions with the silica walls of the capillary channels. We discuss
      the implications for future hybrid electronic and photonic fiber devices.

PMID- 16794693
TI  - Tuning properties of long period gratings in photonic bandgap fibers.
AB  - We investigate the thermal tuning properties of long period gratings (LPGs) in a
      fluid-filled photonic bandgap fiber (PBGF). The combination of strong, resonant
      waveguide dispersion, characteristic of all PBGF modes, and the large thermo
      optic coefficients of fluids yields highly tunable grating resonances. We measure
      grating resonances in three transmission bands with large tuning coefficients of
      up to -1.58 nm/degrees C, which match numerical results. We derive an analytic
      model for the PBGF LPG tuning coefficient to show how it depends on both the
      shift of the transmission bands and the dispersion of the coupled modes.

PMID- 16794694
TI  - Experimental demonstration of similariton pulse compression in a comblike
      dispersion-decreasing fiber amplifier.
AB  - Self-similar propagation of linearly chirped hyperbolic-secant pulses in a
      comblike decreasing-dispersion fiber amplifier has been observed experimentally
      for the first time to our knowledge. The scheme takes advantage of an exact
      solution of the generalized nonlinear Schrodinger equation with distributed
      coefficients.

PMID- 16794695
TI  - Effect of dispersion on nonlinear phase noise.
AB  - The variance of nonlinear phase noise is analyzed by including the effect of
      intrachannel cross-phase modulation-induced nonlinear phase noise. Consistent
      with Ho and Wang [IEEE Photon. Technol. Lett.17, 1426 (2005)] for a lightwave
      transmission system but contrary to the conclusions of both Kumar [Opt. Lett.30,
      3278 (2005)] and Green [Opt. Lett.28, 2455 (2003)] with different initial
      conditions, the variance of nonlinear phase noise does not decrease much with the
      increase of chromatic dispersion. The results are consistent with each other
      after a careful reexamination.

PMID- 16794696
TI  - Fiber-optic color synthesizer.
AB  - Full-color synthesis was achieved, for what we believe is the first time,
      utilizing a novel 3x1 hard polymer-clad fiber coupler along with red, green, and
      blue (RGB) LED primaries. By using RGB LEDs that are coupled to three input
      ports, the device rendered full color from the output port with a circular
      emitting pixel of 135 microm in diameter with an extended color gamut. The
      proposed fiber-optic color synthesizer can provide a compact waveguide solution
      for the beam scanning display and the tunable pure white source for LED
      backlighting.

PMID- 16794697
TI  - Vibrating soliton pairs in a mode-locked laser cavity.
AB  - We show numerically the existence of vibrating soliton pairs that are consistent
      with observations performed with a passively mode-locked fiber laser. These
      vibrating pairs are new types of multisoliton complexes that exist in the
      vicinity of the phase-locked soliton pairs discovered a few years ago [Opt.
      Lett.27, 966 (2002)]. The pairs are found numerically with a laser propagation
      model that includes nonlinear dissipation and cavity periodicity, and they can
      appear following a Hopf-type bifurcation when a cavity parameter is tuned.

PMID- 16794698
TI  - Fiber-Bragg-grating-assisted surface plasmon-polariton sensor.
AB  - A theoretical scheme for a new surface plasmon-polariton (SPP) fiber sensor with
      a fiber Bragg grating imprinted into the fiber core for SPP excitation is
      presented for the first time to our knowledge. In our scheme the energy in the
      fiber core mode can be transferred to a SPP with high efficiency by means of a
      properly designed short-period fiber Bragg grating (SPG). Developed for the
      cylindrical (fiber) geometry, our scheme without loss of generality can be
      applied to a planar geometry. Our simulations are based on the coupled-mode
      method and are performed at telecommunications wavelengths.

PMID- 16794699
TI  - Generalized three-dimensional windowed Fourier transform for fringe analysis.
AB  - A 3D windowed Fourier transform is proposed for fringe sequence analysis, which
      processes the joint spatial and temporal information of the fringe sequence
      simultaneously. The 2D windowed Fourier transform in the spatial domain and the
      1D windowed Fourier transform in the temporal domain are two special cases of the
      proposed method. The principles of windowed Fourier filtering and windowed
      Fourier ridges are developed. Experimental verification shows encouraging results
      despite a longer processing time.

PMID- 16794700
TI  - Correlated imaging with shaped spatially partially coherent light.
AB  - Using a classical source generating a field with an adjustable degree of spatial
      coherence, we propose and demonstrate a two-photon correlated Fourier imaging
      scheme in which both amplitude and phase information about the spatial
      frequencies of an object can be obtained. The effects of the incident field's
      partial coherence are discussed in a geometrical optics approach.

PMID- 16794701
TI  - Impact of telescope seeing on laser adaptive optics.
AB  - Atmospheric turbulence in the internal light path of a telescope produces
      noncommon path phase differences that degrade the image quality of adaptive
      optics systems employing laser guide stars. The spatial covariance and rms
      wavefront errors produced by this effect are derived. It is found that the tilt
      removed wavefront error ranges from about 12 nm for a representative 30 m
      telescope to 59 nm for a 100 m telescope of similar optical design. For adaptive
      optics systems that aim to derive tip-tilt information from the laser guide stars
      the error is considerably larger, ranging from 22 nm for the 30 m telescope to
      256 nm for the 100 m telescope. This effect can be a significant impediment to
      the performance of such systems.

PMID- 16794702
TI  - Subwavelength imaging with a multilayer silver film structure.
AB  - A Ag/SiO2 multilayer imaging structure is shown to have subwavelength
      performance. Loss is the major limitation, and selection of low-loss materials
      and suitable operating wavelengths has a significant impact on performance. The
      influence of the variables is presented, and vortices are shown to exist.

PMID- 16794703
TI  - Subwavelength confinement in an integrated metal slot waveguide on silicon.
AB  - We demonstrate propagation losses of less than 0.8 dB/microm in a metal slot
      waveguide on silicon with a predicted confinement substantially below the optical
      wavelength (approximately 1.55 microm). We also show compact and efficient
      coupling of the high-confinement metal slot waveguide with a standard silicon
      dielectric waveguide with a coupling efficiency of approximately 2.5 dB per
      facet.

PMID- 16794704
TI  - Single-molecule detection sensitivity using planar integrated optics on a chip.
AB  - We present a fully planar integrated optical approach to single-molecule
      detection based on microfabricated planar networks of intersecting solid and
      liquid-core waveguides. We study fluorescence from dye molecules in liquid-core
      antiresonant reflecting optical waveguides, and demonstrate subpicoliter
      excitation volumes, parallel excitation through multiple pump waveguides, and
      single-molecule detection sensitivity. Integrated silicon photonics combined with
      single-molecule detection in solution create a compact, robust, and sensitive
      platform that has applications in numerous fields ranging from atomic physics to
      the life sciences.

PMID- 16794705
TI  - Evidence of the photonic gap contribution to the guiding mechanism for strongly
      confined modes in the refractivelike domain.
AB  - The group index dispersion and birefringence of guided modes supported by
      straight photonic crystal (PhC) waveguides are theoretically and experimentally
      investigated as a function of the waveguide width within various reduced
      frequency domains. Within the photonic gap and far from the Brillouin zone edges,
      strongly confined modes supported by narrow PhC guides exhibit both a group index
      and a birefringence larger than those of a deep ridge. These two results evidence
      the contribution of the photonic gap to the guiding mechanism in the
      refractivelike domain.

PMID- 16794706
TI  - Photonic bus with loop signal routing and multichannel wavelength selection on a
      single silicon-on-insulator platform.
AB  - We have demonstrated a silicon-on-insulator-based photonic bus with integrated
      splitters, a demultiplexer, attenuators, and a multiplexer for loop signal
      routing and multichannel optical wavelength selection. The integrated photonic
      bus has demonstrated a 33+ dB optical cross talk, a 32+ dB extinction ratio, and
      a rise time of 7.6 micros with two-stage Mach-Zehnder attenuators.

PMID- 16794707
TI  - Silicon-on-insulator irregular waveguide mode converters.
AB  - Irregular waveguide elements in a silicon-on-insulator platform that allow new
      device concepts are introduced. Specific designs are achieved using a
      multiresolution optimization strategy where the waveguide width is varied in
      stepwise increments. Simulation results are given for high-efficiency waveguide
      mode converters, power splitters, and waveguide transitions operating at 1.55
      microm. The degrees of freedom available permit these functions and small
      dimensions, making these devices candidates for optical integrated circuits.

PMID- 16794708
TI  - Coherent polarization locking with near-perfect combining efficiency.
AB  - We demonstrate the coherent locking of two orthogonal polarized lasers by using
      polarization selective loss. The two orthogonal polarizations are locked
      coherently to produce a resultant polarization state that sees minimal cavity
      loss. In contrast to the Michelson locking schemes, our scheme has the advantage
      of easy tunability, which helps to routinely achieve near-perfect (>99%)
      combining efficiency even when the power of the two arms is highly imbalanced and
      is varied from a power ratio of unity to >5. We also demonstrate an interesting
      phenomenon in which a miniscule injection of an antiphase field component from
      one arm into another can significantly inhibit the locking mechanism.

PMID- 16794709
TI  - Generation of a radially polarized laser beam by use of the birefringence of a c
      cut Nd:YVO4 crystal.
AB  - We demonstrated the generation of a radially polarized laser beam from an
      extremely simple laser resonator including a c-cut Nd:YVO4 crystal as a laser
      medium. The oscillation in the radial polarization was based on the optical path
      difference between an extraordinary ray and an ordinary ray induced by the
      birefringence of the crystal. By simply adjusting the distance between two cavity
      mirrors, only the extraordinary ray became stable for the oscillation, resulting
      in the generation of a radially polarized beam. The beam was very stable even at
      low power output and is expected to be a promising radially polarized laser
      source because of its excellent simplicity.

PMID- 16794710
TI  - Pulsed and cw laser oscillations in LiF:F-2 color center crystal under laser
      diode pumping.
AB  - Continuous-wave laser oscillations in LiF:F-2 crystal optically pumped by a laser
      diode at 970 nm were demonstrated for what is believed to be the first time. The
      slope efficiency of 14% and conversion efficiency of 5.5% were achieved for 80
      micros pump pulse duration and 5 Hz pulse repetition rate. An efficiency twice as
      low was measured at a 6.25 kHz pulse repetition rate (50% off-duty factor) and in
      cw mode of laser operation.

PMID- 16794711
TI  - Multidimensional single-molecule imaging in live cells using total-internal
      reflection fluorescence microscopy.
AB  - We have developed a wide-field total-internal-reflection fluorescence microscope
      capable of imaging single molecules in live cells, resolved in both wavelength
      and polarization. We show fluorescence resonance energy transfer between single
      pairs of fluorescent molecules bound to signaling receptors in the plasma
      membrane of live cells and demonstrate the importance of polarization
      discrimination in addition to wavelength separation.

PMID- 16794712
TI  - Near-field observation of subwavelength confinement of photoluminescence by a
      photonic crystal microcavity.
AB  - We present a direct, room-temperature near-field optical study of light
      confinement by a subwavelength defect microcavity in a photonic crystal slab
      containing quantum-well sources. The observations are compared with three
      dimensional finite-difference time-domain calculations, and excellent agreement
      is found. Moreover, we use a subwavelength cavity to study the influence of a
      near-field probe on the imaging of localized optical modes.

PMID- 16794713
TI  - High-order harmonic generation in a tightly focused laser beam.
AB  - The force due to the transverse magnetic field of a laser beam drives an electron
      in the direction of laser propagation, thereby impeding the recollision mechanism
      for high-order harmonic generation. The longitudinal electric field component of
      a tightly focused Gaussian beam can sufficiently counteract the magnetic force to
      enhance the harmonic yield substantially. For tight focusing and a laser
      intensity of 10(18) W/cm2, it can raise the harmonic yield by several orders of
      magnitude.

PMID- 16794714
TI  - Enhancement of the two-wave-mixing gain in a stack of thin nonlinear media by use
      of the Talbot effect.
AB  - We show that the Talbot effect can be used to increase the gain of two-wave
      mixing in a stack of thin nonlinear media. We demonstrate that a large gain
      enhancement is achieved for a few nonlinear elements, provided that they are
      placed at distances that satisfy Talbot recurrences.

PMID- 16794715
TI  - Compensating losses in negative-index metamaterials by optical parametric
      amplification.
AB  - Optical parametric amplification controlled by the auxiliary electromagnetic
      field enables transparency, amplification, and oscillation with no cavity in
      strongly absorbing negative-index metamaterials. The opposite directions of the
      wave vector and the Poynting vector in such materials result in extraordinary
      optical properties, including "backward" phase matching and the generation of
      entangled pairs of left- and right-handed counterpropagating photons.

PMID- 16794716
TI  - Multipole-mode surface solitons.
AB  - We discover multipole-mode solitons supported by the surface between two distinct
      periodic lattices imprinted in Kerr-type nonlinear media. Such solitons are
      possible because the refractive index modulation at both sides of the interface
      glues together their out-of-phase individual constituents. Remarkably, we find
      that the new type of solitons may feature highly asymmetric shapes, and yet they
      are stable over wide domains of their existence, a rare property to be attributed
      to their surface nature.

PMID- 16794717
TI  - Simultaneous three-photon-excited violet upconversion luminescence of
      Ce3+:Lu2Si2O7 single crystals by femtosecond laser irradiation.
AB  - We found that Ce3+:Lu2Si2O7 single crystals could be excited at 800 nm by using a
      femtosecond Ti:sapphire laser. The emission spectra of Ce3+:Lu2Si2O7 crystals
      were the same for one-photon excitation at 267 nm as for excitation at 800 nm.
      The emission intensity of Ce3+:Lu2Si2O7 crystals was found to depend on the cube
      of the laser power at 800 nm, consistent with simultaneous absorption of three
      800 nm photons. The measured value of the three-photon absorption cross section
      is sigma'3=2.44x10(-77) cm6 s2.

PMID- 16794718
TI  - Real-time monitoring of all-optical poling by two-beam second-harmonic
      generation.
AB  - We demonstrate a simple method for monitoring all-optical poling in real time.
      The poling pattern created by the writing beam at the fundamental frequency and
      the seed beam at the second-harmonic frequency is reconstructed by two-beam
      second-harmonic generation because of the writing beam and an additional probe
      beam at the fundamental frequency. When the probe beam is sufficiently weak, it
      does not distort the poling process. The method provides a significantly stronger
      signal than monitoring based on a probe beam alone.

PMID- 16794719
TI  - Soliton control in fading optical lattices.
AB  - We predict new phenomena, such as soliton steering and soliton fission, in
      optical lattices that fade away exponentially along the propagation direction.
      Such lattices, featuring tunable decay rates, arise in photorefractive crystals
      in the wavelength range 360-400 nm. We show that the predicted phenomena offer
      different opportunities for soliton control.

PMID- 16794720
TI  - Depolarization of white light generated by ultrashort laser pulses in optical
      media.
AB  - We report measurements of the extinction ratio (ER) of white light generated upon
      irradiation of BK7 glass by ultrashort (36 fs) laser pulses with incident power
      approximately 10(3) times larger than the critical power for self-focusing. At
      low incident powers, the continuum is symmetric about the incident laser
      wavelength; at high powers it becomes broader and distinctly asymmetric towards
      the blue side. We observe that ER degrades by 100-fold after the onset of
      multiphoton-induced free-electron generation (at incident intensity approximately
      2 TW cm-2), which also corresponds to the onset of asymmetry in white-light
      spectra.

PMID- 16794721
TI  - Integrated all-optical pulse restoration with coupled nonlinear microring
      resonators.
AB  - We numerically demonstrate the feasibility of constructing an all-optical pulse
      restorer by using a microresonator structure with Kerr nonlinearity. We obtain a
      clear nonlinear power transfer curve capable of improving the signal-to-noise
      ratio and reducing the bit error rate for digital signals. Since we take
      advantage of field enhancement at resonance, this integrated reshaper could be
      much smaller than other gates based on nonlinear fibers or waveguides.

PMID- 16794722
TI  - Narrow-linewidth near-degenerate optical parametric generation achieved with
      quasi-group-velocity-matching in lithium niobate waveguides.
AB  - We demonstrate narrow-linewidth near-degenerate optical parametric generation in
      reverse-proton-exchange lithium niobate waveguides with quasi-group-velocity
      matching, which is realized by using wavelength-selective directional couplers
      and tight-radius bends. With appropriate designs for 1.6 ps long pump pulses at
      785.1 nm we obtained near-degenerate signal (idler) pulses with a time-bandwidth
      product as low as 1.1, compared with 10.5 for conventional devices without quasi
      group-velocity-matching. This improvement in the temporal property is a result of
      both a pulse compression effect and a filter effect coming from our scheme of
      quasi-group-velocity-matching.

PMID- 16794723
TI  - Precise optical modeling for LED lighting verified by cross correlation in the
      midfield region.
AB  - A novel LED modeling algorithm for precise three-dimensional light pattern
      simulation is proposed and demonstrated. We propose to use normalized cross
      correlation to verify the validity of the simulation in one-dimensional intensity
      patterns as well as two-dimensional irradiance patterns in various midfield
      distances and to provide feedback to achieve a successful model. The model is
      demonstrated to obtain an average of 99% in normalized cross correlation between
      the simulation light pattern and experimental measurement for a truncated inverse
      pyramid LED.

PMID- 16794724
TI  - Transflective liquid-crystal display using low-twisted vertically aligned mode.
AB  - We present the design of a transflective and low-power LCD using a low-twist
      vertically aligned liquid crystal (LC) cell, achieved by blending a chiral
      additive with a patterned reflector in a single-domain configuration. Unlike the
      conventional single-domain transflective LCD, in which it is possible to optimize
      only one of the transmissive and reflective regions, the device suggests that it
      is possible to optimize both the transmission and reflection design to obtain
      favorable results in both reflective and transmissive light conditions by
      optimizing the chiral pitch and twist angle. From the parameter space diagram
      (PSD) method, which does not include the information on chiral pitch and the
      nonuniform LC director tilt angle, optimization focused on the transmissive
      region is performed. By analyzing the relation between the transmittance and the
      chiral pitch under the applied voltage, the optimized twist angle and chiral
      pitch are proposed. It is described that the optimized twist angle is also
      available for the reflective region by the dynamic PSD method by considering the
      average tilt angle under applied voltage.

PMID- 16794725
TI  - Rotational transformations and transverse energy flow in paraxial light beams:
      linear azimuthons.
AB  - Paraxial beams whose transverse structure rotates upon free propagation (spiral
      beams) can be treated as analogs of azimuthons recently found in nonlinear media
      [Phys. Rev. Lett.95, 203904 (2005)]. These linear azimuthons have essentially a
      nonlocalized character and can possess an almost arbitrary rotation rate
      independent of the angular momentum of the beam. Such beams can be assimilated
      into fluent mechanical bodies with intrinsic mass flows determined by transverse
      energy redistribution over the beam cross section.

PMID- 16794726
TI  - Description of Wiener bounds of multicomponent composites by barycentric
      coordinates.
AB  - Wiener bounds for effective complex permittivity of multicomponent composites are
      treated by use of barycentric coordinates, a convex hull, and conformal mapping
      in a complex plane. Depending on the complexity of the multiphase system, the
      bounds provide singly or multiply connected regions that can be used in
      estimating the limits of the effective permittivity of the composite. The present
      modeling is important, e.g., in estimating spectral properties of nanocomposites
      in engineering and nanomedicine and in terahertz-based security imaging.

PMID- 16794727
TI  - Polarization and image rotation induced by a rotating dielectric rod: an optical
      angular momentum interpretation.
AB  - When light is transmitted along the axis of a rotating glass rod, the
      polarization of the light is rotated through a small angle [Proc. R. Soc. London,
      Ser. A349, 423 (1976)]. Under the same conditions, we predict a rotation of the
      transmitted image by exactly the same angle. The treatment of the two effects in
      terms of light's spin and orbital angular momentum suggests that they share a
      common origin.

PMID- 16794728
TI  - Stokes parameters and polarization contrasts in Young's interference experiment.
AB  - We derive a spectral interference law that governs the behavior of the four
      Stokes parameters in Young's two-pinhole experiment with a random electromagnetic
      beam. In addition to the visibility of intensity fringes, we introduce three new
      contrast parameters that describe the interference-induced changes in the field's
      state of partial polarization. The polarization modulation depends on the
      electric field correlations at the pinholes and is closely related to the two
      point Stokes parameters. The results are expected to be particularly useful in
      polarization interferometry and electromagnetic coherence theory. The formalism
      is demonstrated with specific examples.

PMID- 16794729
TI  - Observation of nondegenerate cavity modes for a distorted polystyrene
      microsphere.
AB  - Nondegenerate azimuthal morphology-dependent resonances are observed for a
      distorted, fluorescently labeled polystyrene microsphere levitated in a
      quadrupole ion trap. Modeling the individual resonances by using perturbation
      theory allows a determination of quadrupole and octupole distortion parameters.
      The particle's shape changes slowly over the course of the measurement and
      eventually becomes spherical. The morphological changes are facilitated by laser
      heating of the particle above the polystyrene glass transition temperature. We
      demonstrate a method of transforming a trapped particle to a sphere and rendering
      its azimuthal modes degenerate.

PMID- 16794730
TI  - Adaptive correction of a tightly focused, high-intensity laser beam by use of a
      third-harmonic signal generated at an interface.
AB  - By using the third-harmonic signal generated at an air-dielectric interface, we
      demonstrate a novel way of correcting wavefront aberrations induced by high
      numerical-aperture optics. The third harmonic is used as the input physical
      parameter of a genetic algorithm working in closed loop with a 37-actuator
      deformable mirror. This method is simple and reliable and can be used to correct
      aberrations of tightly focused beams, a regime where other methods have
      limitations. Improvement of the third-harmonic signal generated with an f/1.2
      parabolic mirror by 1 order of magnitude is demonstrated.

PMID- 16794731
TI  - Self-referencing spectral phase interferometry for direct electric-field
      reconstruction with chirped pulses.
AB  - We analyze the characterization of strongly chirped pulses by spectral phase
      interferometry for direct electric-field reconstruction (SPIDER). We show how to
      extend the working range of this technique for these relevant cases and derive
      correction factors for typical operating parameters. The results are
      straightforward to implement in the calculation algorithms. We demonstrate the
      validity of this technique by characterizing numerically and experimentally
      pulses with a known spectral phase profile.

PMID- 16794732
TI  - Brewster-angled chirped mirrors for broadband pulse compression without
      dispersion oscillations.
AB  - We use Brewster-angled chirped mirrors for dispersion compensation of a
      noncollinear optical parametric amplifier. This novel mirror design virtually
      eliminates spurious surface reflections and resultant dispersion ripple. The
      absence of compression artifacts is demonstrated by the generation of clean 5.6
      fs pulses, with what is believed to be an unprecedented low ripple-induced
      satellite content for a nonadaptive scheme. In addition, the 270 THz spectral
      coverage allows generation of widely tunable visible pulses of 8 to 15 fs
      duration.

PMID- 16794733
TI  - Superluminal pulse reflection from a weakly absorbing dielectric slab.
AB  - Group delay for a reflected light pulse from a weakly absorbing dielectric slab
      is theoretically investigated, and large negative group delay is found for weak
      absorption near a resonance of the slab [Re(kd)=mpi]. The group delay for both
      the reflected and transmitted pulses will be saturated with an increase of the
      absorption.

PMID- 16794734
TI  - KSHV targets multiple leukocyte lineages during long-term productive infection in
      NOD/SCID mice.
AB  - To develop an animal model of Kaposi sarcoma-associated herpesvirus (KSHV)
      infection uniquely suited to evaluate longitudinal patterns of viral gene
      expression, cell tropism, and immune responses, we injected NOD/SCID mice
      intravenously with purified virus and measured latent and lytic viral transcripts
      in distal organs over the subsequent 4 months. We observed sequential escalation
      of first latent and then lytic KSHV gene expression coupled with electron
      micrographic evidence of virion production within the murine spleen. Using novel
      technology that integrates flow cytometry with immunofluorescence microscopy, we
      found that the virus establishes infection in murine B cells, macrophages, NK
      cells, and, to a lesser extent, dendritic cells. To investigate the potential for
      human KSHV-specific immune responses within this immunocompromised host, we
      implanted NOD/SCID mice with functional human hematopoietic tissue grafts
      (NOD/SCID-hu mice) and observed that a subset of animals produced human KSHV
      specific antibodies. Furthermore, treatment of these chimeric mice with
      ganciclovir at the time of inoculation led to prolonged but reversible
      suppression of KSHV DNA and RNA levels, suggesting that KSHV can establish latent
      infection in vivo despite ongoing suppression of lytic replication.

PMID- 16794735
TI  - Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads
      to diet-sensitive obesity.
AB  - Leptin and insulin have been identified as fuel sensors acting in part through
      their hypothalamic receptors to inhibit food intake and stimulate energy
      expenditure. As their intracellular signaling converges at the PI3K pathway, we
      directly addressed the role of phosphatidylinositol3,4,5-trisphosphate-mediated
      (PIP3-mediated) signals in hypothalamic proopiomelanocortin (POMC) neurons by
      inactivating the gene for the PIP3 phosphatase Pten specifically in this cell
      type. Here we show that POMC-specific disruption of Pten resulted in hyperphagia
      and sexually dimorphic diet-sensitive obesity. Although leptin potently
      stimulated Stat3 phosphorylation in POMC neurons of POMC cell-restricted Pten
      knockout (PPKO) mice, it failed to significantly inhibit food intake in vivo.
      POMC neurons of PPKO mice showed a marked hyperpolarization and a reduction in
      basal firing rate due to increased ATP-sensitive potassium (KATP) channel
      activity. Leptin was not able to elicit electrical activity in PPKO POMC neurons,
      but application of the PI3K inhibitor LY294002 and the KATP blocker tolbutamide
      restored electrical activity and leptin-evoked firing of POMC neurons in these
      mice. Moreover, icv administration of tolbutamide abolished hyperphagia in PPKO
      mice. These data indicate that PIP3-mediated signals are critical regulators of
      the melanocortin system via modulation of KATP channels.

PMID- 16794736
TI  - Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing
      intratumoral drug uptake.
AB  - Tumor-associated fibroblasts are key regulators of tumorigenesis. In contrast to
      tumor cells, which are genetically unstable and mutate frequently, the presence
      of genetically more stable fibroblasts in the tumor-stromal compartment makes
      them an optimal target for cancer immunotherapy. These cells are also the primary
      source of collagen type I, which contributes to decreased chemotherapeutic drug
      uptake in tumors and plays a significant role in regulating tumor sensitivity to
      a variety of chemotherapies. To specifically kill tumor-associated fibroblasts,
      we constructed an oral DNA vaccine targeting fibroblast activation protein (FAP),
      which is specifically overexpressed by fibroblasts in the tumor stroma. Through
      CD8+ T cell-mediated killing of tumor-associated fibroblasts, our vaccine
      successfully suppressed primary tumor cell growth and metastasis of multidrug
      resistant murine colon and breast carcinoma. Furthermore, tumor tissue of FAP
      vaccinated mice revealed markedly decreased collagen type I expression and up to
      70% greater uptake of chemotherapeutic drugs. Most importantly, pFap-vaccinated
      mice treated with chemotherapy showed a 3-fold prolongation in lifespan and
      marked suppression of tumor growth, with 50% of the animals completely rejecting
      a tumor cell challenge. This strategy opens a new venue for the combination of
      immuno- and chemotherapies.

PMID- 16794738
TI  - Characteristics of Atropa belladonna hairy roots cryopreserved by vitrification
      method.
AB  - Atropa belladonna hairy roots (clone M8) were successfully cryopreserved by using
      the vitrification method. A. belladonna hairy root tips were precultured on a
      half strength of Murashige and Skoog (MS) solid medium with 0.1 mg per L 2,4-D or
      without phytohormone for 1 day, and then dehydrated with PVS2 solution for 15
      minutes prior to immersion into liquid nitrogen for 1 day, 1 week, 1 month and 3
      months. Hairy root tips kept in liquid nitrogen were rapidly thawed at 36 degree
      C in a water bath. The root tips were recultured on half strength MS medium. The
      hairy root tips, precultured with 2,4-D before cryopreservation, showed a higher
      survival rate than those precultured without phytohormone. The hairy root tips,
      precultured with 2,4-D, showed an average survival rate of 83 percent. There was
      no significant difference in the viability of the hairy roots cryopreserved for
      different periods. The regrowth of cryopreserved hairy roots was similar to that
      of untreated hairy roots and tropane alkaloid productivity became stable after
      4th subculture. PCR analysis of hairy roots demonstrated the conservation of the
      T-DNA in cryopreserved hairy roots. These results indicate that cryopreservation
      by vitrification method is useful to preserve A.belladonna hairy root clone M8.

PMID- 16794737
TI  - In vivo antigen delivery by a Salmonella typhimurium type III secretion system
      for therapeutic cancer vaccines.
AB  - Bacterial vectors may offer many advantages over other antigen delivery systems
      for cancer vaccines. We engineered a Salmonella typhimurium vaccine strain to
      deliver the NY-ESO-1 tumor antigen (S. typhimurium-NY-ESO-1) through a type III
      protein secretion system. The S. typhimurium-NY-ESO-1 construct elicited NY-ESO-1
      specific CD8+ and CD4+ T cells from peripheral blood lymphocytes of cancer
      patients in vitro. Oral administration of S. typhimurium-NY-ESO-1 to mice
      resulted in the regression of established NY-ESO-1-expressing tumors.
      Intratumoral inoculation of S. typhimurium-NY-ESO-1 to NY-ESO-1-negative tumors
      resulted in delivery of antigen in vivo and led to tumor regression in the
      presence of preexisting NY-ESO-1-specific CD8+ T cells. Specific T cell responses
      against at least 2 unrelated tumor antigens not contained in the vaccine were
      observed, demonstrating epitope spreading. We propose that antigen delivery
      through the S. typhimurium type III secretion system is a promising novel
      strategy for cancer vaccine development.

PMID- 16794739
TI  - Optimising cryopreservation protocols for haematopoietic progenitor cells: a
      methodological approach for umbilical cord blood.
AB  - Current cryopreservation protocols for haematopoietic cells have developed
      largely empirically and there is no consensus on an optimal method of
      preservation. These protocols, though providing sufficient cells to permit
      engraftment, can lead to cell loss of the order of 50 percent. In the context of
      umbilical cord blood such losses are unacceptable. Whilst an empirical approach
      can provide an acceptable level of recovery, the cryopreservation process can
      only be optimised by adopting a methodological approach. This paper provides an
      overview of just such an approach as illustrated by a study on CD34 cells from
      umbilical cord blood. It involves firstly the determination of membrane
      permeability parameters that can then be used to model safe addition and elution
      protocols for the chosen cryoprotectant, in this case dimethyl sulphoxide. This
      in turn permits cryoprotectant toxicity to be evaluated free from the confounding
      effect of osmotic damage caused by inappropriate addition and elution protocols.
      Finally, non-toxic concentrations of cryoprotectant may be investigated in a
      cooling rate study to provide an optimal cryopreservation protocol. Using the
      model, the effect on CD34 cells of current addition and elution protocols was
      also examined.

PMID- 16794740
TI  - Changes in intracellular potassium and sodium content of 2-cell mouse embryos
      induced by exposition to vitrification concentrations of ethylene glycol.
AB  - Intracellular concentration of potassium and sodium in two-cell mouse embryos in
      G1/S phase after exposition to vitrification solutions containing ethylene glycol
      (EG) and sucrose or after incubation in Dulbecco solution were measured by
      electron probe microanalysis (EPMA). The embryos at room temperature were treated
      in 10 percent EG for 10 min, transferred into mixture of EG and 1.0 M sucrose in
      ratio of 3:7 (v/v) for 3 min, then to 0.5 M sucrose for 10 min followed by
      washing the cells with Dulbecco;s solution for 10 min prior to analysis. The
      cytoplasmic concentration of potassium and sodium in controlled untreated with EG
      embryos were in a range of 116-130 mM of potassium and 120 mM of sodium, with
      good concordance in two identical experiments. After exposition that mimicked
      vitrification protocols, the intracellular potassium dropped almost two-three
      fold (47 + 3 mM in one experiment and to 70 mM in the second experiment. The
      intracellular sodium concentration also decreased two-fold in range 60-70 mM
      after treatment with EG. Possible mechanisms of changes in the intracellular
      elemental concentrations including the high intracellular sodium observed in
      intact embryos are discussed.

PMID- 16794741
TI  - Implementation of garlic cryopreservation techniques in the national plant
      germplasm system.
AB  - The USDA-ARS National Plant Germplasm System (NPGS) maintains more than 200
      Allium sativum (garlic) accessions at the Western Regional Plant Introduction
      Station in Pullman, WA. All accessions must be grown out in the field annually
      since garlic plants from these accessions do not reliably produce seeds and bulbs
      do not store well. Shoot tips excised from garlic cloves can be successfully
      cryopreserved using either Plant Vitrification Solution 2 (PVS2; 15 percent v/v
      DMSO, 15 percent v/v ethylene glycol, 30 percent v/w glycerol, 0.4 M sucrose) or
      Plant Vitrification Solution 3 (PVS3; 50 percent v/w sucrose, 50 percent v/w
      glycerol). We compared regrowth of shoot tips representing diverse garlic
      germplasm after exposure to either PVS2 or PVS3 during the cryopreservation
      procedure. At the USDA-ARS National Center for Genetic Resources Preservation, a
      component of the NPGS, we consider accessions successfully preserved if a minimum
      of 40 percent of explants exhibit regrowth after liquid nitrogen exposure and at
      least 60 viable shoot tips remain in long-term storage. Ten of twelve diverse
      garlic accessions were successfully cryopreserved using either PVS2 or PVS3 as
      cryoprotectants. Five genotypes had the best post liquid nitrogen regrowth after
      exposure to PVS2, four genotypes had the best regrowth after exposure to PVS3,
      and three genotypes performed equally well using either cryoprotectant solution.
      This project is part of an ongoing program to cryopreserve accessions of NPGS
      clonal crop collections.

PMID- 16794742
TI  - Effect of tetrasodium tripolyphosphate on the freeze-concentrated glass-like
      transition temperature of sugar aqueous solutions.
AB  - The freeze-concentrated glass-like transition temperatures (Tg2), so-called ante
      melting temperature or ice-melting temperature of tripolyphosphate-sugar aqueous
      solutions prepared with various sugars (ribose, sorbitol, glucose, maltose,
      sucrose, and trehalose) were investigated by using differential scanning
      calorimetry to evaluate the effect of tetrasodium tripolyphosphate on the Tg2 of
      sugar aqueous solutions. The Tg2 of tripolyphosphate-sugar aqueous solutions were
      higher than those of tripolyphosphate or sugar aqueous solutions and converged in
      a narrow temperature range of 238 to 243 K. Furthermore, a study of the Tg2 of
      tripolyphosphate-glucose aqueous solutions adjusted to various ratios indicated
      that the Tg2 increment depended on the ratio and that another glass-like
      transition appeared at a temperature below the Tg2 by increasing the ratio of
      tripolyphosphate. The drastic increase in the Tg2 of sugars with the addition of
      tripolyphosphate will be useful for improving the cryostabilization of
      biomaterials.

PMID- 16794743
TI  - Modeling the heat transfer problem for the novel combined cryosurgery and
      hyperthermia system.
AB  - A multidimensional, finite element analysis (FEA) for the freezing, holding,
      rewarming and heating processes of biological tissues during the cryosurgery
      process of the new Combined Cryosurgery/Hyperthermia System is presented to
      theoretically test its validity. The tissues are treated as nonideal materials
      freezing over a temperature range, and the thermophysical properties of which are
      temperature dependent. The enthalpy method is applied to solve the highly
      nonlinear problem. It was found that when the same boundary condition and the
      same target tissue presented, the novel Cryosurgery/Hyperthermia System could
      supply the target tissue an approximative cooling rate, a much lower minimal
      temperature, a much greater warming rate, and a much greater thermal gradients
      compared with that of the simplified Endocare system. The numerical simulation
      indicates that the novel combined cryosurgery and hyperthermia system can provide
      an excellent curative effect in the corresponding cryotherapy. And the most
      attractive feature of this FEA framework is that it can be easily mastered by the
      surgeon without in-depth theory of heat transfer to analyze the cryosurgery
      process beforehand due to the friendly GUI (graphical user interface) of Ansys
      software.

PMID- 16794744
TI  - Hypothermic renal preservation with a sucrose/ polyethylene glycol solution in a
      rabbit renal transplant model.
AB  - Renal preservation at for 24 hours at hypothermia was studied in a rabbit model
      after flush cooling with sucrose-based solution (SBS), compared with a standard
      preservation solution (in this case, Marshall's Hypertonic Citrate solution -
      HCA). Polyethylene glycol supplementation to SBS (SBS-PEG) was also investigated.
      Renal function was measured by plasma creatinine assays during 1 months post
      transplantation, and pathology of the explanted kidneys was undertaken. Results
      showed that survival at 28 days was similar in all groups, (HCA - 3 out of 6; SBS
      - 2 out of 5; SBS-PEG - 3 out of 5), and there were no differences in recovery of
      plasma creatinine values. Histopathological evaluation of the grafts indicated
      that SBS preservation resulted in more severe damage after transplantation (P
      less than 0.05 in both corticomedullary region and medulla compared to HCA),
      whilst addition of PEG reduced the damage score to that seen with HCA. SBS can be
      used as a simple, inexpensive preservation solution for kidney cold storage
      provided that PEG is used as an additional colloid.

PMID- 16794745
TI  - Universal use of inactivated polio vaccine.
AB  - OBJECTIVES: To present an update on the status of poliomyelitis worldwide, number
      of cases per year, regions most affected by the disease, vaccines currently
      available, their risks and benefits, monovalent vaccine use, risks of
      disseminating a mutant virus in the community, progress that has been made in
      terms of worldwide eradication and the World Health Organization's (WHO)
      proposals in this transition period between global eradication and the post
      eradication period. SOURCES OF DATA: Data for the period from 1955 to 2005 were
      searched in MEDLINE, LILACS, The Web, Doctor's Guide, WHO website and the Pan
      American Health Organization (PAHO) website and text book. SUMMARY OF THE
      FINDINGS: In 1988, the WHO established the goal of eradicating the disease and
      interrupting transmission of the wild virus globally. Since then, there has been
      a dramatic decline of the disease, although in 2005 there were still some
      countries considered endemic and others where polio returned on account of
      imported viruses. The vaccines used worldwide are the classical tOPV and IPV, and
      in this eradication process, the use of mOPV vaccines has been encouraged in
      places where only one type of poliovirus circulates. In addition to spreading the
      virus in the community, the OPV vaccines may, however, cause paralyses by
      reversal of the neurovirulence process. CONCLUSIONS: For a world free of
      poliomyelitis disease, it would be necessary to interrupt circulation of the
      virus, which will only be possible if the OPV virus were to be discontinued, in
      accordance with the WHO proposals for this transition period and the post
      eradication period.

PMID- 16794746
TI  - Safety, immunogenicity and efficacy of influenza vaccine in children.
AB  - OBJECTIVES: To review the immunogenicity, safety and efficacy of inactivated and
      attenuated trivalent influenza vaccines in children. SOURCES OF DATA: Database
      search of the medical literature indexed on MEDLINE, LILACS and in the Cochrane
      Library. Review articles, clinical trials and epidemiological studies published
      from 1990 to 2006 were selected for analysis. SUMMARY OF THE FINDINGS: Influenza
      is an infectious disease that is both universal and seasonal, with incidence in
      all age groups and annual epidemics characterized by excessive morbidity and
      mortality. The elderly and people with comorbidity are high risk groups for
      severe influenza. It has recently been proven that healthy infants suffer similar
      morbidity to other risk groups, and therefore vaccination against influenza is
      indicated for them too, as being the most effective means of preventing infection
      by the influenza virus. The safety of influenza vaccines in children appears
      adequate, with the most often observed adverse effects being local reactions or
      fever. Immunogenicity in children varies from 30 to 90%, being directly
      proportional to age. Efficacy depends on the primary objective and can range from
      levels comparable with placebo to up to 91% efficacy against confirmed influenza
      A infection. Schoolchildren play an important role in the dissemination of the
      influenza virus, and population studies have demonstrated herd immunity.
      CONCLUSIONS: Trivalent influenza vaccines, whether inactivated or attenuated,
      have low reactogenicity and offer variable immunogenicity and efficacy in
      children. Vaccination is effective for prevention of infections by the influenza
      virus and for reducing morbidity. More powerful studies of efficacy and safety in
      infants are still required.

PMID- 16794747
TI  - Spontaneously relapsing and remitting primary CNS lymphoma in an immunocompetent
      45-year-old man.
AB  - A 45-year-old immunocompetent man with primary central nervous system lymphoma
      (PCNSL) presented with multiple spontaneous relapses and remissions in the
      absence of steroid treatment. Because of the fluctuations with improvement in
      both the clinical course and MRI findings, alternative disorders were considered
      that led to delay of diagnosis and treatment prior to brain biopsy. This case and
      a handful of others with single remissions emphasize that PCNSL cannot be
      reliably ruled out by improving or disappearing symptoms, signs or traditional MR
      imaging abnormalities.

PMID- 16794748
TI  - Images in neuro-oncology: choroid plexus carcinoma.

PMID- 16794749
TI  - The presence of necrosis and/or microvascular proliferation does not influence
      survival of patients with anaplastic oligodendroglial tumours: review of 98
      patients.
AB  - Accurate prognosis for patients with anaplastic oligodendroglial gliomas is
      increasingly difficult to make. Characterisation of these tumours remains
      challenging, increasing proportions of oligodendroglial diagnoses in gliomas are
      reported, and no WHO 2000 grade IV exists for them, so that highly anaplastic
      tumours can only be grouped with glioblastoma (GBM) or with grade III
      oligodendroglioma, which have differing clinical behaviour. Longer survival times
      reported for patients with glioblastoma containing an oligodendroglial element
      (GBMO) suggest that a grade IV for oligodendroglial tumours might exist. In
      patients with anaplastic gliomas containing an oligodendroglial element, we
      explored whether microvascular proliferation (MVP) and necrosis were associated
      with shorter survival, sufficient to create a grade IV. Biopsies for 98 patients
      with anaplastic oligodendroglioma, anaplastic oligoastrocytoma or tumours with an
      oligodendroglial and GBM element, discharged 1998-2004, were identified from
      databases at three allied neurosurgery units. Pathology reports were reviewed for
      the presence of MVP and necrosis. Anaplastic oligoastrocytoma and GBMO were
      combined to measure the effect of an astrocytic element on survival. For
      anaplastic oligodendroglioma patients, median survival time was 24 months, while
      for anaplastic oligoastrocytoma or GBMO patients, it was 9 months. Age 60 or over
      (P=0.006) and astrocytic element (P=0.01) were the only independent predictors of
      survival. Patients 60 and over with an astrocytic element had 4.6 times the risk
      of death of patients under 60 with anaplastic oligodendroglioma.A grade IV cannot
      be created using necrosis or MVP since neither feature predicted survival after
      adjustment for age and an astrocytic element. However age and an astrocytic
      element were strong predictors of poorer survival in patients with anaplastic
      oligodendroglial tumours.

PMID- 16794750
TI  - Chronic idiopathic demyelinating polyneuropathy (CIDP) associated with Kaposi's
      sarcoma.

PMID- 16794754
TI  - [Smoking cessation must be professionalized].

PMID- 16794756
TI  - Pyopneumothorax due to Streptococcus milleri.

PMID- 16794755
TI  - [Antipsychotic drug-induced changes in metabolism].
AB  - Antipsychotic medications are a mainstay in the treatment of schizophrenia and
      are widely used in other psychiatric conditions. New generation antipsychotic
      agents (NGAs) are increasingly replacing first generation antipsychotic agents
      (FGAs), mainly due to a decreased risk for extrapyramidal symptoms, better
      overall tolerability, as well as some efficacy advantages. However, some of these
      NGAs are associated with adverse metabolic effects such as substantial weight
      gain, the induction of insulin resistance and lipid disorders. Among these
      substances, clozapine and olanzapine induce the most significant weight gain,
      olanzapine mainly by increasing body fat and both of these antipsychotics have
      been associated with disturbances in glucose metabolism. Diabetes mellitus
      induced by treatment with some NGAs occurred in many cases within days to weeks
      after initiation of SGA therapy, in some cases hyperglycemia promptly resolved
      after discontinuation of the medication and several reports have documented
      recurrent hyperglycemia after a rechallenge with the same drug. One possible
      pathomechanism for hyperglycemia induced by these NGAs is the induction of
      insulin resistance via humoral and/or cellular pathways. Alternatively, NGA
      induced diabetes may occur because of weight gain or a change in body fat
      distribution with a shift to a predominantly visceral fat type or through a
      direct effect on insulin sensitive target tissues. In this article we like to
      review the metabolic side effects of NGA treatment, highlight recent advances in
      the pathogenesis of these metabolic complications and discuss potential
      treatments of these side effects.

PMID- 16794757
TI  - An unrecognized epidemic of Mycoplasma pneumoniae infection in Vienna.
AB  - Mycoplasma pneumoniae infection shows epidemiological peaks with a 2- to 10-fold
      increased incidence every four to seven years. The regional epidemiology of M.
      pneumoniae infection is important with regard to empirical antibiotic treatment
      of community-acquired respiratory tract infections, which are the most common
      cause for visiting a physician. To date, no data on the epidemiology of M.
      pneumoniae in central Europe have been published. In the present study, the
      results of M. pneumoniae serology performed at the Clinical Division of Virology
      at Vienna General Hospital (a 2,140-bed university teaching hospital with an
      average of 94,000 admissions/year and 430,000 outpatient visits/year) in the 10
      year period from January 1995 to December 2004 were analyzed retrospectively.
      Antibody titers > or = 1:64 in complement fixation tests were considered
      indicative of acute or recent mycoplasma infection. The annual total number of
      serum specimens tested for anti-M. pneumoniae antibodies remained stable
      throughout the study period (median: 2859 samples/year, range: 2257-3338). The
      annual median number of patients with high M. pneumoniae titers was 13. A major
      epidemiological peak (43 patients) was observed in 2000, the epidemic starting in
      late 1999 and ending in 2001. A surveillance or reporting system for M.
      pneumoniae infections (i.e. positive serological results for M. pneumoniae) would
      be useful for physicians caring for patients with community-acquired respiratory
      tract infections.

PMID- 16794758
TI  - Prevalence of patients continuing to smoke after vascular interventions.
AB  - INTRODUCTION: Smoking is one of the most important risk factors for the
      development and progression of atherosclerosis. Smoking cessation is an
      obligatory element in the management of vascular problems and in patients
      scheduled for vascular interventions. The aim of this study was to assess the
      prevalence of patients smoking before and after vascular surgical procedures and
      to evaluate the requirements for inpatient programs for smoking cessation and
      nicotine replacement therapy. METHODS: 500 patients admitted for vascular
      interventions were included in this prospective study. Smoking status was
      evaluated both objectively and subjectively. All patients underwent measurements
      of exhaled breath carbon monoxide to quantify nicotine dependency and all
      answered a standardized Fagerstrom questionnaire both on admission and after
      surgery to identify current smokers. RESULTS: Of 500 vascular patients included
      in the study, only 70 (14 %) never had smoked, 243 (49 %) had given up smoking
      before admission and 161 (32 %) were current smokers. Of the current smokers, 64
      (40 %) did not smoke during hospitalization but 97 (60 %) continued to smoke in
      hospital. Of these 97 patients, 78 (80 %) were men and 19 women; their mean age
      was 61 +/- 4 years (range 40-84). Four patients had surgery for infrarenal aortic
      aneurysm, 40 underwent carotid endarterectomy and 53 had peripheral arterial
      occlusive disease (PAD). There was no difference between abstinent patients and
      continuing smokers in previous cigarette consumption or Fagerstrom score, a
      predictor for long-term smoking behavior. Patients with carotid artery stenosis
      were significantly more abstinent while hospitalized (P = 0.006); patients with
      PAD, however, were more likely to continue smoking as inpatients (P = 0.004).
      Sixty-five percent of continuing smokers stated that they would stop smoking in
      hospital if counseling and nicotine replacement therapy were provided. With
      regard to their predominant location of atherosclerosis, patients with PAD were
      less willing than those with carotid stenosis to abstain from smoking while
      hospitalized (53 % vs 88 %, respectively; P < 0.001). CONCLUSION: A substantial
      proportion of patients admitted for vascular surgery are smokers. More than half
      of these continue to smoke in the hospital, an environment where smoking is
      prohibited by law. Counseling, nicotine replacement therapy and smoking-cessation
      programs are urgently needed for vascular surgical inpatients.

PMID- 16794759
TI  - The Mosque Campaign: a cardiovascular prevention program for female Turkish
      immigrants.
AB  - BACKGROUND: The Women's Health Office of the State of Tyrol, Austria, provides
      cardiovascular disease (CVD) prevention programs for women. However, local
      Turkish women have not participated in our programs. The aim of the so-called
      Mosque Campaign was to conduct a Turkish-language, culture-sensitive CVD
      prevention program tailored to the needs of Turkish women to improve their
      knowledge of CVD risk factors and to minimize ethnic differences in participation
      rates for preventive programs. METHODS: The pilot program was conducted in all 28
      mosques in Tyrol during the years 1999/00, 2000/01 and 2001/02. A Turkish
      educational lecture and the opportunity for a private medical consultation were
      provided, and 2,446 Turkish women completed a questionnaire on their personal
      knowledge of CVD. In addition a total of 1,992 blood pressure readings were
      taken. RESULTS: Most of the women belonged to the first generation of female
      immigrants and reported not using German-language media. About one-third of the
      women considered themselves to be obese. More than 13 % had raised systolic
      and/or diastolic blood pressure. We observed a significant decrease in
      unawareness of the main CVD risk factors from 1999/00 to 2001/02: unawareness of
      cholesterol level decreased from 57.4 % to 32.4 % (p < 0.001), of blood pressure
      from 41.3 % to 29.6 % (p < 0.001) and of blood glucose from 49.7 % to 25.2 % (p <
      0.001). CONCLUSIONS: Even though Austria provides free access to healthcare
      services, a large number of Turkish women were not aware of their CVD risk
      factors. The Mosque Campaign reached female Turkish migrants and was effective in
      reducing their level of unawareness about CVD. Language-adapted and culture
      sensitive programs are necessary to ensure greater equality for ethnic minority
      groups.

PMID- 16794760
TI  - 3-D Conformal radiotherapy of localized prostate cancer within an Austrian-German
      multicenter trial: a prospective study of patients' acceptance of the rectal
      balloon during treatment.
AB  - PURPOSE: Patients with localized prostate cancer are treated with 3D radiotherapy
      using a rectal balloon catheter for internal immobilization of the prostate,
      thereby reducing the radiation dose to the dorsal rectal wall. The purpose of the
      study was to investigate clinical feasibility and the influence of acute rectal
      side effects and pre-existing hemorrhoids on patients' acceptance of the rectal
      balloon catheter. METHODS AND MATERIALS: 442 patients who underwent primary
      radiation therapy for localized prostate cancer were included in this prospective
      Austrian-German multicenter trial. The total radiation dose was either 70 Gy or
      74 Gy. Acute rectal side effects were documented using the EORTC/RTOG grading
      score (European Organisation for Research and Treatment of Cancer/Radiation
      Therapy 225 Oncology Group) at weeks 2, 4 and 7 of radiation treatment. Within
      the same time intervals patients were interviewed about their tolerance of the
      rectal balloon catheter, evaluating five categories of acceptance (1 = no major
      complaints, 2 = pain at/during application, 3 = signs of blood at the balloon
      catheter after application but without any pain, 4 = signs of blood at the
      balloon catheter after application and pain, 5 = balloon application had to be
      stopped). Voluntary rectoscopy prior to radiotherapy was performed in 310
      patients. RESULTS: 429/442 patients (97 %) were treated with the balloon
      catheter. No major complaints were reported in 79 % of the patients and no acute
      rectal side effects were seen in 52 % of the patients. Grade 1 side effects were
      seen in 31 % patients, Grade 2 in 17 % and Grade 3 in 0.5 %. Balloon use had to
      be stopped in only 4 % of the patients. There was significant correlation between
      balloon discomfort and rectal side effects (p < 0.01). The presence of
      hemorrhoids in 36 % patients prior to irradiation had no influence on balloon
      tolerance. CONCLUSIONS: The rectal balloon can be used in 3D radiotherapy of
      localized prostate cancer with a high degree of acceptance by the patients. Use
      of the balloon is safe within daily clinical treatment. Patients reporting acute
      rectal side effects experienced significantly more balloon discomfort, but the
      presence of hemorrhoids was not found to influence acceptance of the balloon.

PMID- 16794761
TI  - Temozolomide for recurrent or progressive high-grade malignant glioma: results of
      an Austrian multicenter observational study.
AB  - BACKGROUND: The use of chemotherapy in patients with malignant gliomas has
      remained a controversial issue even after the publication of favorable study data
      and a meta-analysis. The present study was initiated to support the use of
      chemotherapy in patients with relapsed high-grade gliomas (HGG). PATIENTS AND
      METHODS: Six Austrian centers recruited 43 patients with histologically confirmed
      HGG at first recurrence. Twelve chemotherapy-naive patients received oral
      temozolomide at a dose of 200 mg/m(2) once a day for five consecutive days and 26
      patients a dose of 150 mg/m(2) also for five days after various first-line
      chemotherapies. TMZ treatment was repeated every four weeks for a total of six
      cycles. RESULTS: Twenty-one patients (52.5 %) received at least six cycles of
      therapy. Two patients experienced complete remission and eight patients a partial
      response. Twenty patients survived at one year after enrolment in the study;
      eight patients survived beyond three years of follow-up. Hematological toxicities
      consisted of three thrombocytopenias G4 and 35 lymphocytopenias G3 and G4; these
      did not cause interstitial pneumonia or require inpatient treatment. Non
      hematological toxicities were rare and without clinical relevance. Patients'
      quality of life was maintained during treatment. CONCLUSION: The study data
      confirm the feasibility and efficacy of chemotherapy with temozolomide in
      patients with relapsed/progressive HGG.

PMID- 16794762
TI  - A woman with red eyes and hypokalemia: a case of acquired Gitelman syndrome.
AB  - Gitelman syndrome is a rare hereditary disorder of the thiazide-sensitive NaCl
      transporter in the distal renal tubular cells, but mimicking of such hereditary
      tubular disorders has been described in different autoimmune diseases (Sjogren
      syndrome, SLE, ...). A 62-year-old woman with painful red eyes and sicca syndrome
      presented at the ophthalmological department. The diagnostic evaluation
      identified a Sjogren syndrome with early endophthalmitis as the reason for the
      red eyes. Results of laboratory examination indicated severe hypokalemia,
      metabolic alkalosis and hypomagnesemia, although this had not been seen years
      earlier. Together with the urine analysis, a rare case of an acquired Gitelman
      syndrome was diagnosed. Substitution with potassium and magnesium improved the
      initial symptoms of weakness, but renal electrolyte wasting persisted even after
      treatment of Sjogren syndrome. In patients with autoimmune disease, laboratory
      analysis of serum electrolytes should be performed because different acquired
      tubular disorders can lead to severe hypokalemia.

PMID- 16794763
TI  - From a sore throat to the intensive care unit: the Lemierre syndrome.
AB  - Lemierre syndrome is characterized by an acute oropharyngeal infection,
      suppurative thrombophlebitis of the internal jugular vein and metastatic
      infections. The infection is usually caused by Fusobacterium necrophorum. We
      report on a 19-year-old male patient who was admitted with a five-day history of
      fever, sore throat and progressive dyspnea. Computed tomography of the neck and
      chest revealed a parapharyngeal abscess, jugular vein thrombosis, descending
      necrotizing mediastinitis and multiple areas of bilateral consolidation and
      cavitations within the lungs. Fusobacterium necrophorum was identified in the
      blood culture. Early combined abscess drainage with neck and chest incisions,
      together with broad spectrum intravenous antibiotic treatment and medical
      management in an intensive care unit resulted in a good clinical outcome.

PMID- 16794765
TI  - Women's reproductive health and depression: a community survey in the Gambia,
      West Africa.
AB  - BACKGROUND: Depression is the commonest mental illness in developing countries
      and impoverished women are most at risk. Formal mental health services in these
      situations are rare. Depression commonly co-presents with physical symptoms or
      else is unspectacular, so the condition often goes unrecognised. To strengthen
      the prevention and management of depression, information is required on easily
      recognisable correlates of depression. This study explored associations between
      depression and reproductive health conditions in rural African women of
      reproductive age. METHODS: A community-based reproductive health survey among
      rural women aged 15-54 years in The Gambia, West Africa, included screening with
      a modified Edinburgh Depression Scale (EDS), a reproductive health questionnaire
      and a gynaecological examination. Depression was then assessed clinically and
      data for 565 women were used to estimate the prevalence of depression and examine
      associations with reproductive health conditions and demographic factors.
      RESULTS: The weighted prevalence of depression was 10.3% (95% CI 8.3-12.7). Being
      depressed was most significantly associated with widowhood or divorce (adjusted
      Odds Ratio (aOR) 8.42, 2.77-25.57), infertility (3.69, 1.42-9.65) and severe
      menstrual pain (3.94, 1.52-10.27). There were significant differences between
      ethnic groups. Being in the postpartum period was not associated with an
      increased likelihood of depression. CONCLUSION: This study points to the
      importance of reproductive potential and reproductive health in maintaining
      women's mental well-being across different strata of a rural and resource-poor
      society. It could provide an initial focus for the management of women with
      depression as well as directing future research in reproductive health and
      psychiatry.

PMID- 16794766
TI  - Somatization in the population: from mild bodily misperceptions to disabling
      symptoms.
AB  - OBJECTIVE: This study investigates the prevalence of current somatization in the
      population by taking different levels of symptom severity into account.
      Somatization is described along a continuum from mild and negligible bodily
      misperceptions to severe and disabling somatoform symptoms. METHODS: A
      representative sample of 2.552 persons in Germany was examined with a screening
      instrument for medically unexplained physical complaints that had occurred during
      the past 7 days. All 53 symptoms from the ICD-10/DSM-IV sections of somatoform
      disorders were included. RESULTS: 81.6% reported at least one symptom causing at
      least mild impairment and 22.1% at least one symptom causing severe impairment.
      The entire sample had an average of 6.6 symptoms associated with at least mild
      distress. Somatization of any degree was associated with female gender, age above
      45, lower educational level, lower household income and rural area. The most
      common symptoms with prevalence rates > 20% were various types of pain (back,
      head, joints, extremities), food intolerance, sexual indifference, painful
      menstruations and erectile/ejaculatory dysfunction. CONCLUSION: This population
      survey demonstrates that medically unclear complaints are an everyday phenomenon.
      About three out of four cases are below clinical relevance with only low level of
      impairment. Epidemiological correlates are similar between clinical and non
      clinical forms of somatization.

PMID- 16794767
TI  - High-level expression of a recombinant fragment of human fibronectin containing
      the Cell I-Hep II-IIICS71 domain in Escherichia coli as a soluble protein.
AB  - Fibronectin (FN) is a major matrix protein that is involved in multiple
      processes. Its Cell I-Hep II domain is potentially useful in tumor therapy. Here,
      a recombinant fragment of FN with the Cell I-Hep II-IIICS71 domain, CH/71, was
      expressed in Escherichia coli. The CH/71 fusion protein consists of Cell I-Hep II
      domain and 19th to 89th amino acids of IIICS domain of FN. The expression level
      of CH/71 in E. coli was very high after induction with IPTG. Furthermore, CH/71
      protein was largely found in the soluble fraction. It was readily purified by one
      step heparin-agarose affinity chromatograph. The ability of CH/71 binding cells
      was about 8-fold of that of Cell I-Hep II domain FN.

PMID- 16794768
TI  - Electron capture dissociation mass spectrometry in characterization of peptides
      and proteins.
AB  - Electron capture dissociation (ECD) represents one of the most recent and
      significant advancements in tandem mass spectrometry (MS/MS) for the
      identification and characterization of polypeptides. In comparison with the
      conventional fragmentation techniques, such as collisionally activated
      dissociation (CAD), ECD provides more extensive sequence fragments, while
      allowing the labile modifications to remain intact during backbone fragmentation-
      an important attribute for characterizing post-translational modifications.
      Herein, we present a brief overview of the ECD technique as well as selected
      applications in characterization of peptides and proteins. Case studies including
      characterization and localization of amino acid glycosylation, methionine
      oxidation, acylation, and "top-down" protein mass spectrometry using ECD will be
      presented. A recent technique, coined as electron transfer dissociation (ETD),
      will be also discussed briefly.

PMID- 16794769
TI  - Biological synthesis of semiconductor zinc sulfide nanoparticles by immobilized
      Rhodobacter sphaeroides.
AB  - A novel, clean biological transformation reaction by immobilized Rhodobacter
      sphaeroides has been developed for the synthesis of zinc sulfide (ZnS)
      nanoparticles with an average diameter of 8 nm. The nanoparticles were examined
      by X-ray diffraction, transmission electron microscopy, energy dispersive
      analyses of X-rays, UV-vis optical absorption and photoluminescence spectra. The
      average diameter of ZnS nanoparticles varied according to the culture time.

PMID- 16794770
TI  - Anti-prelog reduction of prochiral carbonyl compounds by Oenococcus oeni in a
      biphasic system.
AB  - An aqueous-organic biphasic system was established and used with whole cells of
      Oenococcus oeni to reduce 2-octanone to (R)-2-octanol. The conversion reached 99%
      when the Tris/borate buffer was increased from 50 mM to 300 mM in the aqueous
      phase. In addition, the conversion increased as the log P value of the organic
      solvent changed from 0.5 to 6.6. Under optimized conditions, the conversion of
      (R)-2-octanol reached 99% from 0.5 M 2-octanone with an optical purity of 99%
      e.e. The biphasic system allows the anti-Prelog reduction of aliphatic and
      aromatic ketones to furnish (R)-configurated alcohols in high optical purity as
      well.

PMID- 16794771
TI  - Improvement in yield and purity of a recombinant malaria vaccine candidate based
      on the receptor-binding domain of Plasmodium vivax Duffy binding protein by codon
      optimization.
AB  - A recombinant blood-stage vaccine for Plasmodium vivax malaria based on the
      functional receptor-binding domain of PvDBP (PvRII) has been developed. A
      synthetic gene coding for PvRII was expressed in Escherichia coli using codon
      optimization. Expression level of recombinant PvRII was 10% of the total cellular
      proteins. Truncated PvRII products, seen when the native PvRII gene was
      expressed, were absent in case of synthetic gene.

PMID- 16794772
TI  - Fungicidal and cytotoxic activity of a Capsicum chinense defensin expressed by
      endothelial cells.
AB  - Plant defensins are antimicrobial peptides that exhibit mainly antifungal
      activity against a broad range of plant fungal pathogens. However, their actions
      against Candida albicans have not been extensively studied. The mRNA for gamma
      thionin, a defensin from Capsicum chinense, has been expressed in bovine
      endothelial cells. The conditioned medium of these cells showed antifungal
      activity on germ tube formation (60-70% of inhibition) and on the viability of C.
      albicans (70-80% of inhibition). Additionally, C. albicans was not able to
      penetrate transfected cells. Conditioned medium from these cells also inhibited
      the viability (80%) of the human tumor cell line, HeLa.

PMID- 16794773
TI  - Cloning and expression of two plant proteins: similar antimicrobial activity of
      native and recombinant form.
AB  - Antimicrobial peptides and proteins are being studied with increasing interest
      because of their broad range antimicrobial activity. Among plant antimicrobial
      proteins, the wheat seed polypeptides, puroindoline a and puroindoline b, are
      particularly interesting because of their established antibacterial activity. In
      this paper we describe different strategies used to clone His tagged and GST
      tagged puroindolines obtaining 1.5 mg recombinant protein from 1 l culture. The
      antimicrobial activity of recombinant and native puroindolines was comparable.

PMID- 16794774
TI  - Immunogenicity of a novel, bivalent, plant-based oral vaccine against hepatitis B
      and human immunodeficiency viruses.
AB  - A synthetic chimeric gene, TBI-HBS, encoding the immunogenic ENV and GAG epitopes
      of human immunodeficiency virus (HIV-1) and the surface protein antigen (HBsAg)
      of hepatitis B virus (HBV), was expressed in tomato plants. Tomato fruits
      containing the TBI-HBS antigen were fed to experimental mice and, on days 14 and
      28 post-feeding, high levels of HIV- and HBV-specific antibodies were present in
      the serum and feces of the test animals. Intraperitoneal injection of a DNA
      vaccine directing synthesis of the same TBI-HBsAg antigen boosted the antibody
      response to HIV in the blood serum; however, it had no effect on the high level
      of antibodies produced to HBV.

PMID- 16794775
TI  - Multifocal visual evoked responses to dichoptic stimulation using virtual reality
      goggles: Multifocal VER to dichoptic stimulation.
AB  - Multifocal visual evoked potentials (mfVEPs) have demonstrated good diagnostic
      capabilities in glaucoma and optic neuritis. This study aimed at evaluating the
      possibility of simultaneously recording mfVEP for both eyes with dichoptic
      stimulation using virtual reality goggles and also to determine the stimulus
      characteristics that yield maximum amplitude. ten healthy volunteers were
      recruited and temporally sparse pattern pulse stimuli were presented
      dichoptically using virtual reality goggles. Experiment 1 involved recording
      responses to dichoptically presented checkerboard stimuli and also confirming
      true topographic representation by switching off specific segments. Experiment 2
      involved monocular stimulation and comparison of amplitude with Experiment 1. In
      Experiment 3, orthogonally oriented gratings were dichoptically presented.
      Experiment 4 involved dichoptic presentation of checkerboard stimuli at different
      levels of sparseness (5.0 times/s, 2.5 times/s, 1.66 times/s and 1.25 times/s),
      where stimulation of corresponding segments of two eyes were separated by 16.7,
      66.7,116.7 & 166.7 ms respectively. Experiment 1 demonstrated good traces in all
      regions and confirmed topographic representation. However, there was suppression
      of amplitude of responses to dichoptic stimulation by 17.9+/-5.4% compared to
      monocular stimulation. Experiment 3 demonstrated similar suppression between
      orthogonal and checkerboard stimuli (p = 0.08). Experiment 4 demonstrated maximum
      amplitude and least suppression (4.8%) with stimulation at 1.25 times/s with
      166.7 ms separation between eyes. It is possible to record mfVEP for both eyes
      during dichoptic stimulation using virtual reality goggles, which present
      binocular simultaneous patterns driven by independent sequences. Interocular
      suppression can be almost eliminated by using a temporally sparse stimulus of
      1.25 times/s with a separation of 166.7 ms between stimulation of corresponding
      segments of the two eyes.

PMID- 16794776
TI  - Slip vs. viscoelasticity in dewetting thin films.
AB  - Ultrathin polymer films on non-wettable substrates display dynamic features which
      have been attributed to either viscoelastic or slip effects. Here we show that in
      the weak- and strong-slip regime, effects of viscoelastic relaxation are either
      absent or essentially indistinguishable from slip effects. Strong slip modifies
      the fastest unstable mode in a rupturing thin film, which questions the standard
      approach to reconstruct the effective interface potential from dewetting
      experiments.

PMID- 16794777
TI  - Numerical study of the stress response of two-dimensional dense granular
      packings.
AB  - We investigate the Green function of two-dimensional dense random packings of
      grains in order to discriminate between the different theories of stress
      transmission in granular materials. Our computer simulations allow for a detailed
      quantitative investigation of the dynamics which is difficult to obtain
      experimentally. We show that both hyperbolic and parabolic models of stress
      transmission fail to predict the correct stress distribution in the studied
      region of the parameters space. We demonstrate that the compressional and shear
      components of the stress compare very well with the predictions of isotropic
      elasticity for a wide range of pressures and porosities and for both frictional
      and frictionless packings. However, the states used in this study do not include
      the critical isostatic point for frictional particles, so that our results do not
      preclude the fact that corrections to elasticity may appear at the critical point
      of jamming, or for other sample preparation protocols, as discussed in the main
      text. We show that the agreement holds in the bulk of the packings as well as at
      the boundaries and we validate the linear dependence of the stress profile width
      with depth.

PMID- 16794779
TI  - Interactions between impermeant blocking ions in the cystic fibrosis
      transmembrane conductance regulator chloride channel pore: evidence for anion
      induced conformational changes.
AB  - It is well known that extracellular Cl(-) ions can weaken the inhibitory effects
      of intracellular open channel blockers in the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl(-) channel pore. This effect is frequently
      attributed to repulsive ion-ion interactions inside the pore. However, since Cl(
      ) ions are permeant in CFTR, it is also possible that extracellular Cl(-) ions
      are directly competing with intracellular blocking ions for a common binding
      site; thus, this does not provide direct evidence for multiple, independent anion
      binding sites in the pore. To test for the possible through-space nature of ion
      ion interactions inside the CFTR pore, we investigated the interaction between
      impermeant anions applied to either end of the pore. We found that inclusion of
      low concentrations of impermeant Pt(NO(2))(4) (2-) ions in the extracellular
      solution weaken the blocking effects of three different intracellular blockers
      [Pt(NO(2))(4) (2-), glibenclamide and 5-nitro-2-(3-phenylpropylamino)benzoic
      acid] without affecting their apparent voltage dependence. However, the effects
      of extracellular Pt(NO(2))(4) (2-) ions are too strong to be accounted for by
      simple competitive models of ion binding inside the pore. In addition,
      extracellular Fe(CN)(6) (3-) ions, which do not appear to enter the pore, also
      weaken the blocking effects of intracellular Pt(NO(2))(4) (2-) ions. In contrast
      to previous models that invoked interactions between anions bound concurrently
      inside the pore, we propose that Pt(NO(2))(4) (2-) and Fe(CN)(6) (3-) binding to
      an extracellularly accessible site outside of the channel permeation pathway
      alters the structure of an intracellular anion binding site, leading to weakened
      binding of intracellular blocking ions.

PMID- 16794778
TI  - Properties of shaker-type potassium channels in higher plants.
AB  - Potassium (K(+)), the most abundant cation in biological organisms, plays a
      crucial role in the survival and development of plant cells, modulation of basic
      mechanisms such as enzyme activity, electrical membrane potentials, plant turgor
      and cellular homeostasis. Due to the absence of a Na(+)/K(+) exchanger, which
      widely exists in animal cells, K(+) channels and some type of K(+) transporters
      function as K(+) uptake systems in plants. Plant voltage-dependent K(+) channels,
      which display striking topological and functional similarities with the voltage
      dependent six-transmembrane segment animal Shaker-type K(+) channels, have been
      found to play an important role in the plasma membrane of a variety of tissues
      and organs in higher plants. Outward-rectifying, inward-rectifying and weakly
      rectifying K(+) channels have been identified and play a crucial role in K(+)
      homeostasis in plant cells. To adapt to the environmental conditions, plants must
      take advantage of the large variety of Shaker-type K(+) channels naturally
      present in the plant kingdom. This review summarizes the extensive data on the
      structure, function, membrane topogenesis, heteromerization, expression,
      localization, physiological roles and modulation of Shaker-type K(+) channels
      from various plant species. The accumulated results also help in understanding
      the similarities and differences in the properties of Shaker-type K(+) channels
      in plants in comparison to those of Shaker channels in animals and bacteria.

PMID- 16794780
TI  - Biophysical and pharmacological characteristics of native two-pore domain TASK
      channels in rat adrenal glomerulosa cells.
AB  - Multiple genes of the TASK subfamily of two-pore domain K(+) channels are
      reported to be expressed in rat glomerulosa cells. To determine which TASK
      isoforms contribute to native leak channels controlling resting membrane
      potential, patch-clamp studies were performed to identify biophysical and
      pharmacological characteristics of macroscopic and unitary K(+) currents
      diagnostic of recombinant TASK channel isoforms. Results indicate K(+)
      conductance (gK(+)) is mediated almost exclusively by a weakly voltage-dependent
      (leak) K(+) channel closely resembling TASK-3. Leak channels exhibited a unitary
      conductance approximating that expected for TASK-3 under the recording conditions
      employed, brief mean open times and a voltage-dependent open probability.
      Extracellular H(+) induced voltage-independent inhibition of gK(+), exhibiting an
      IC(50) of 56 nM: (pH 7.25) and a Hill coefficient of 0.75. Protons inhibited leak
      channel open probability (P(o)) by promoting a long-lived closed state (tau > 500
      ms). Extracellular Zn(2+) mimicked the effects of H(+); inhibition of gK(+)
      exhibited an IC(50) of 41 microM: with a Hill coefficient of 1.26, inhibiting
      channel gating by promoting a long-lived closed state. Ruthenium red (5 microM: )
      inhibited gK(+) by 75.6% at 0 mV. Extracellular Mg(2+) induced voltage-dependent
      block of gK(+), inhibiting unitary current amplitude without affecting mean open
      time. Bupivacaine induced voltage-dependent block of gK(+), exhibiting IC(50)
      values of 116 microM: at -100 mV and 28 microM: at 40 mV with Hill coefficients
      of 1 at both potentials. Halothane induced a voltage-independent stimulation of
      gK(+) primarily by decreasing the leak channel closed-state dwell time.

PMID- 16794781
TI  - Inclusion of the transcervical approach in video-assisted thoracoscopic extended
      thymectomy (VATET) for myasthenia gravis: a prospective trial.
AB  - BACKGROUND: Because evidence-based data regarding the quality of video-assisted
      thoracoscopic thymectomy for the treatment of myasthenia gravis are lacking, a
      prospective trial comparing three different operative approaches was conducted to
      evaluate their efficacy. METHODS: This prospective study enrolled 20 consecutive
      patients with nonthymomatous myasthenia gravis. A series of three approaches for
      bilateral video-assisted thoracoscopic extended thymectomy (VATET) using the
      anterior chest wall-lifting method (original), the original method with a flexed
      neck position (modified), and the original method with a transcervical approach
      (final) were prospectively performed in each patient for quantitative and
      pathologic evaluation of the residual thymus after each approach. RESULTS:
      Complete VATET required 242 +/- 48 min, with the transcervical procedure
      requiring 23 +/- 12 min. After the modified method, the residual thymus in the
      cervical region was 1.5 cm in size and weighed 0.8 g (0.8% of the entire thymus),
      as compared with a size of 2.2 cm and a weight of 1.3 g (3.2%) after the original
      method. Each value is the result of comparison with the final method.
      Histopathologic studies showed residual tissue in the germinal center as well as
      Hassall's corpuscles in more than 70% of cases. CONCLUSION: The findings show
      that VATET without the transcervical approach could be an immunologically
      incomplete treatment for myasthenia gravis. Therefore, the transcervical approach
      should be included in VATET procedures to ensure radicality.

PMID- 16794782
TI  - Day case laparoscopic herniorraphy. A NICE procedure with a long learning curve.
AB  - BACKGROUND: The aim of this study was to evaluate day case laparoscopic
      herniorraphy (LH) and to ascertain the impact of trainee surgeons on its
      performance. METHODS: We performed a prospective study of ambulatory laparoscopic
      transabdominal preperitoneal herniorraphies performed in a dedicated day surgical
      unit between March 1996 and October 2003. RESULTS: A total of 840 herniorraphies
      were performed in 706 consecutive patients. Surgery was performed by 15 higher
      surgical trainees and three consultant surgeons. The mean operating times for
      trainees were longer for unilateral (48.4 +/- 0.98 vs 41.4 +/- 0.87 min, p <
      0.05) and bilateral (69.0 +/- 3.24 vs 53.0 +/- 1.68 min, p < 0.05) repairs than
      for consultants. Subgroup analysis demonstrated that after an experience of 40
      procedures, trainee times approached those of the consultants (41.39 +/- 1.17 vs
      41.4 +/- 0.87 min, p= 0.31). LH repair was well tolerated and associated with
      minimal postoperative pain and nausea. Mean pain scores postoperatively and at 24
      h were 2.69 +/- 0.11 and 2.07 +/- 0.09, respectively. Mean nausea scores
      postoperatively and at 24 h were 0.34 +/- 0.06 and 0.22 +/- 0.06, respectively.
      Ninety-three percent of patients (n = 657) were discharged within 8 h. There were
      two conversions to an open procedure (0.1%) and two significant complications
      (0.1%). Ninety-five percent of patients who responded to our questionnaire (n =
      398/419) were satisfied with surgery and would undergo day case laparoscopic
      herniorraphy again. CONCLUSIONS: Laparoscopic herniorraphy is a safe technique
      suitable for day case surgery. Operator experience dictates duration of surgery.
      Trainees' operating times approach those of consultants after 40 procedures.
      Prolonged operating times and increased cost are not justifiable reasons for not
      recommending LH.

PMID- 16794783
TI  - Myelin basic protein: a multifunctional protein.
AB  - Myelin basic protein (MBP), the second most abundant protein in central nervous
      system myelin, is responsible for adhesion of the cytosolic surfaces of
      multilayered compact myelin. A member of the 'intrinsically disordered' or
      conformationally adaptable protein family, it also appears to have several other
      functions. It can interact with a number of polyanionic proteins including actin,
      tubulin, Ca(2+)-calmodulin, and clathrin, and negatively charged lipids, and
      acquires structure on binding to them. It may act as a membrane actin-binding
      protein, which might allow it to participate in transmission of extracellular
      signals to the cytoskeleton in oligodendrocytes and tight junctions in myelin.
      Some size isoforms of MBP are transported into the nucleus and thus they may also
      bind polynucleotides. Extracellular signals received by myelin or cultured
      oligodendrocytes cause changes in phosphorylation of MBP, suggesting that MBP is
      also involved in signaling. Further study of this very abundant protein will
      reveal how it is utilized by the oligodendrocyte and myelin for different
      purposes.

PMID- 16794784
TI  - tRNA, new aspects in intracellular dynamics.
AB  - The nuclear envelope divides a eukaryotic cell into two compartments, the nucleus
      and the cytoplasm. Transcription and maturation of RNAs encoded on nuclear
      chromosomes are carried out in the nucleus, while the proteins coded by these
      RNAs are translated and processed in the cytoplasm. Cytosolic tRNAs, essential
      factors for translation, are transcribed in the nucleus and undergo extensive
      processing before reaching functionality. It had previously been believed that
      tRNAs have only one-way tickets to pass through the nuclear envelope after
      maturation in the nucleus, and that the small amounts of mature tRNAs found in
      the nucleus are biosynthetic intermediates. However, two reports from our lab and
      Anita Hopper's group recently demonstrated that tRNAs have multi-round commuter
      tickets to shuttle between the nucleus and the cytoplasm in the yeast
      Saccharomyces cerevisiae. In fact, various tRNA species, including aminoacylated
      full-length tRNAs and 3' end-shortened tRNAs, are actively imported into the
      nucleus under various conditions. These findings force a reconsideration of our
      view of intracellular dynamics of tRNAs, and re-evaluations of the physiological
      meanings of the nuclear mature tRNAs.

PMID- 16794785
TI  - Glycolipids and phospholipids as natural CD1d-binding NKT cell ligands.
AB  - Natural killer T (NKT) cells have been shown by a number of studies to play a
      protective role against cancers, autoimmune diseases and infectious diseases.
      Several glycolipids and phospholipids derived from mammalian, bacterial,
      protozoan and plant species have recently been identified as natural ligands
      (antigens) for NKT cells. Some of these glycolipid/phospholipid ligands have now
      been crystallized in forms bound to CD1d molecules, and the tertiary structure of
      these complexes has finally been revealed. This review is intended to list
      natural NKT cell ligands identified to date, and discuss how their structures
      relate to their propensity to bind CD1d molecules and, as a consequence,
      stimulate NKT cells.

PMID- 16794786
TI  - The neuroligin and neurexin families: from structure to function at the synapse.
AB  - Proper brain connectivity and neuronal transmission rely on the accurate assembly
      of neurotransmitter receptors, cell adhesion molecules and several other
      scaffolding and signaling proteins at synapses. Several new exciting findings
      point to an important role for the neuroligin family of adhesion molecules in
      synapse development and function. In this review, we summarize current knowledge
      of the structure of neuroligins and neurexins, their potential binding partners
      at the synapse. We also discuss their potential involvement in several aspects of
      synapse development, including induction, specificity and stabilization. The
      implication of neuroligins in cognitive disorders such as autism and mental
      retardation is also discussed.

PMID- 16794787
TI  - Vasopressin antagonists.
AB  - Effects of vasopressin via V1a- and V2-receptors are closely implicated in a
      variety of water-retaining diseases and cardiovascular diseases, including heart
      failure, hyponatraemia, hypertension, renal diseases, syndrome of inappropriate
      antidiuretic hormone secretion, cirrhosis and ocular hypertension. As vasopressin
      receptors are found in many different tissues, vasopressin antagonists may
      benefit the treatment of disorders such as cerebral ischaemia and stroke,
      Raynaud's disease, dysmenorrhoea and tocolytic treatment. V1b selective
      vasopressin antagonists are discussed in terms of their usefulness in the
      treatment of emotional and psychiatric disorders. The vaptans are vasopressin
      receptor antagonists with V1a (relcovaptan) or V2 (tolvaptan, lixivaptan)
      selectivity or non-selective activity (conivaptan) which may be advantageous in
      some disorders. The V1a/V2 non-selective vasopressin antagonist conivaptan is the
      first vaptan which is approved by the FDA for the treatment of euvolaemic
      hyponatraemia.

PMID- 16794788
TI  - Carvedilol versus Metoprolol for the prevention of atrial fibrillation after off
      pump coronary bypass surgery: rationale and design of the Carvedilol or
      Metoprolol Post-Revascularization Atrial Fibrillation Controlled Trial (COMPACT).
AB  - BACKGROUND: Postoperative new-onset atrial fibrillation (AF) remains the most
      common complication of coronary artery bypass graft surgery. Postoperative AF
      carries the risk of hemodynamic instability, increases the risk of thromboembolic
      events, and has a significant economic impact. Current guidelines recommend
      treatment with beta-blockers to prevent AF; information, however, is limited
      regarding the relative efficacy of beta-blocking agents. Carvedilol is a non
      selective adrenergic blocker with anti-inflammatory, antioxidant, and multiple
      cationic channel blocking properties. These unique properties of carvedilol have
      generated interest in its use as a prophylaxis for postoperative AF. MATERIALS
      AND METHODS: We hypothesize that carvedilol will be more effective than
      metoprolol, a conventional beta(1)-selective antagonist, in suppressing newly
      developed AF following off-pump coronary artery bypass (OPCAB) surgery. We have
      designed the Carvedilol or Metoprolol Post-Revascularization Atrial Fibrillation
      Controlled Trial (COMPACT) to test our hypothesis in a multi-center, open-label,
      randomized, and controlled trial. A total of at least 650 patients will be
      randomized to receive an initial oral dose of either 5 mg of carvedilol twice per
      day or 20 mg of metoprolol tartrate three times per day following surgery. The
      dose of each beta-blocker will be increased to the maximum tolerated dose. The
      primary endpoint is the incidence of new-onset AF during the first 7 days after
      surgery. CONCLUSIONS: The COMPACT is the first multi-center, randomized,
      controlled trial to directly compare two different beta-blockers in patients
      following surgical coronary revascularization. Results of this trial will help to
      guide physicians in choosing appropriate medications following OPCAB surgery.

PMID- 16794790
TI  - Influence of Japan's new Diagnosis Procedure Combination-based payment system on
      the surgical sector: does it really shorten the hospital stay?
AB  - PURPOSE: In 2003, the Diagnosis Procedure Combination (DPC)-based payment system
      was introduced on a trial basis in 82 major Japanese hospitals. We analyzed the
      influence of this system on hospital revenue and expenditure, focusing on whether
      it reduces the length of stay in hospital (LOS), particularly in the surgical
      sector. METHODS: We studied 120 patients hospitalized at the University of Tokyo
      hospital between May and July 2003, including 93 surgical patients who underwent
      operations for gastric, colon, rectal, hepatic, or mammary carcinoma;
      arteriosclerosis obliterans; appendicitis; adult hernia inguinalis; or varicose
      veins, and 27 nonsurgical patients hospitalized for recurrent gastric carcinoma,
      ileus, appendicitis, or mild acute pancreatitis. We analyzed the changes in
      profit per day in patients with a reduced LOS using the simulation model.
      RESULTS: Reducing the LOS of the surgical patients resulted in a greater profit;
      however, there was minimal if any profit increase achieved by reducing the LOS of
      the medical patients. In fact, when material costs were high, profit decreased.
      CONCLUSION: The DPC-based payment system does not usually offer an economic
      incentive to shorten the LOS. Expanding our current system will reduce the LOS
      only in major hospitals, but it will reduce the national average LOS. Thus, the
      current DPC-based payment system needs to be improved further.

PMID- 16794791
TI  - Expanding hematoma after extraperiosteal paraffin plombage.
AB  - PURPOSE: The development of a chronic expanding hematoma after paraffin plombage
      has not yet been reported because the procedure was performed only at a limited
      number of institutes during the short period before the development of
      antituberculous drugs. We herein report eight patients with chronic expanding
      hematoma several decades after undergoing extraperiosteal paraffin plombage.
      METHODS: We reviewed eight surgically treated patients with chronic expanding
      hematoma after undergoing extraperiosteal paraffin plombage. RESULTS: Swelling of
      the plombage space was shown in a chest roentgenogarm and a contrast-enhanced
      computed tomographic scan as an expanding inhomogeneous mass with subcapsular
      enhancements. The patient symptoms included a chest or axillary tumor in three
      patients, and shoulder pain in two, while three were asymptomatic prior to
      radiological evidence of disease progression. No tuberculous bacillus was
      detected on microbacterial examination. Both the paraffin and hematomas were
      removed. The average operative bleeding was 161 ml. One patient underwent muscle
      transposition for postoperative infection of the residual space. Following the
      operation, seven patients remained free from the disease and one had hematoma
      recurrence 9 years later, which was again removed. CONCLUSION: A chronic
      expanding hematoma following extraperiosteal paraffin plombage is a rare
      complication. However, this disease should be considered when a patient who has
      undergone paraffin plombage presents with late complications.

PMID- 16794792
TI  - Clinical and pathologic features of fibroadenoma of the mastopathic type.
AB  - PURPOSE: Fibroadenoma with mastopathic change (FAM) is a relatively uncommon
      subtype of fibroadenoma of the breast, with a high incidence of pathological
      misdiagnosis. This histological subtype remains poorly understood because of its
      rarity. Many questions remain unanswered about its clinicopathological
      importance, especially in the differential diagnosis of breast cancers. METHODS:
      Among 218 breast fibroadenomas surgically resected as excisional biopsies at our
      institute between 1990 and 2004, 19 were pathologically diagnosed as FAM. We
      reviewed these 19 patients. RESULTS: The ages of the patients ranged from 20 to
      51 years (mean 36.8 years). The tumor sizes ranged from 0.8 to 7 cm (mean 2.1
      cm). Six of the 19 patients underwent core needle biopsy, resulting in a
      diagnosis of fibroadenoma in four patients and atypical ductal hyperplasia in two
      patients. Ultrasonography showed findings suggestive of solid tubular carcinoma
      in seven patients, fibroadenoma in ten patients, and unspecific malignant tumors
      in two. They were not specified clinically. CONCLUSION: Recognition of this
      distinctive variant of fibroadenoma is important because it resembles intraductal
      carcinoma and is increasing in incidence. It is crucial to distinguish FAM from
      intraductal carcinoma in biopsy specimens. Thus, not only pathologists but also
      clinicians must be able to recognize this type of fibroadenoma, and cooperate
      closely to establish an accurate diagnosis.

PMID- 16794793
TI  - Large vessel - sternum adhesion after cardiac surgery; a risk-factor analysis.
AB  - PURPOSE: To study the clinical results of resternotomy in patients with dense and
      direct adhesion between the large vessels and the sternum, and define the
      morphologic features of the adhesion. METHODS: Between 2000 and 2003, 67 patients
      with a history of cardiac surgery underwent median resternotomy. We studied each
      patient's profile and the measurements taken from preoperative computed
      tomography scans. We then conducted multivariate logistic regression analysis to
      determine the predictive morphologic features of adhesion between the large
      vessels and the sternum in these 67 patients. RESULTS: Twenty (29.9%) of the 67
      patients had direct adhesion between the large vessels and the sternum. Sternal
      re-entry was performed without injury to the large vessels in 18 (90%) but the
      aorta was injured in 2 (10%) patients, resulting in catastrophic hemodynamic
      disorder and operative death in one. Multivariate logistic regression analysis
      revealed that an extracardiac conduit and a high occupying rate of the aorta and
      pulmonary artery in the mediastinal space were significant morphologic factors.
      CONCLUSION: The morphologic features of large vessels to sternal dense adhesion
      as possible risk factors for injury to the large vessels are the presence of an
      extracardiac conduit and a large ascending aorta or pulmonary artery in relation
      to the mediastinal space.

PMID- 16794794
TI  - Surgical experience of cardiac tumors: early and late results.
AB  - PURPOSE: Cardiac tumors include benign and malignant neoplasms that arise within
      the cardiac chambers or myocardium. This study summarizes our surgical
      experiences with cardiac tumors. METHODS: Between 1975 and 2003, 51 patients with
      cardiac tumors were surgically treated. RESULTS: Myxomas. Forty-seven cardiac
      myxomas were excised in 46 patients with an average age of 51.7 +/- 18 years. The
      preoperative symptoms included congestive heart failure (37%) and embolism (30%).
      The incidence of preoperative embolization was significantly higher in the
      gelatinous and lobated myxomas than in the solid and smooth form (P = 0.017). The
      early mortality rate was 2.2%. Although the late mortality rate was 9.7%, no
      patients died from cardiological causes (mean follow-up, 11.2 years). Only 1
      patient required surgery for recurrence. Benign nonmyxomatous tumors. Three
      patients with a mean age of 26.3 +/- 19.0 years showed benign nonmyxomatous
      tumors. There were no perioperative or late deaths. Malignant tumors. Two
      patients were diagnosed to have malignant tumors and although there was no
      perioperative death, both died postoperatively within 6 months. CONCLUSIONS:
      Cardiac myxomas and nonmyxomatous benign cardiac tumors show excellent results
      after a surgical excision, with a low morbidity and mortality. A surgical
      resection should thus be considered as a treatment option for patients with
      malignant tumors.

PMID- 16794795
TI  - cDNA array analysis for prediction of hepatic metastasis of colorectal carcinoma.
AB  - PURPOSE: Distant metastasis is a significant prognostic factor of colon
      carcinoma. Adjuvant chemotherapy has been shown to decrease its recurrence.
      However, there are no definitive methods for the diagnosis of hepatic recurrence
      after potentially curative surgery. The aim of this study was to evaluate the
      accuracy of mRNA expression profiling using samples obtained from primary tumors
      to predict hepatic recurrence. METHODS: Patients with stage III colorectal
      carcinoma without any recurrence for at least 5 years (group A: n = 9) and
      patients with stage IV carcinoma with hepatic metastasis (group B: n = 10) were
      included in this study. Tissue samples were collected from the primary tumor and
      adjacent normal colonic mucosa at the time of surgery in each patient. Total RNA
      was extracted and the mRNA expression profile was examined using a cDNA
      macroarray. RESULTS: A hierarchical clustering analysis revealed a dendrogram in
      which the patients were divided into two clusters. One cluster consisted of seven
      patients in group A and two in group B. The other consisted of two patients in
      group A and eight in group B. Therefore, the positive and negative predictive
      value of hierarchical clustering analysis for hepatic metastasis was 80.0% and
      78.8%, respectively. Fifteen genes were revealed to be upregulated and 12 were
      downregulated in group B. The upregulated genes included CCNA2, TP53, and MDM2,
      while the downregulated genes included CDH1, GADD45A, and BCL2L2. CONCLUSIONS:
      mRNA expression profiling by a cDNA array analysis of specimens obtained from
      primary tumors was found to be useful for distinguishing patients with and
      without hepatic metastasis. This method is expected to contribute to the
      identification of patients at high risk for hepatic recurrence, while also
      helping in the administration of intensive adjuvant chemotherapy for such high
      risk patients.

PMID- 16794796
TI  - Left ventricular assist system through the left ventricle for acute myocardial
      infarction: report of a case.
AB  - A 49-year-old man, who had suffered from acute myocardial infarction due to left
      main trunk occlusion, developed cardiogenic shock and was successfully treated
      with an implantation of a left ventricular assist system with left ventricular
      apical drainage. At present he is awaiting a heart transplant at approximately
      485 days since the operation. The timely application of a left ventricular assist
      system before the development of multiple organ failure is thus considered to be
      effective for patients demonstrating acute myocardial infarction with cardiogenic
      shock.

PMID- 16794797
TI  - Myositis ossificans of the abdominal rectus muscle: report of a case.
AB  - We herein report a rare case of myositis ossificans originating from the
      abdominal rectus muscle, found in a 38-year-old woman who presented with a left
      upper abdominal mass. The mass was initially suspected to be a malignant neoplasm
      because no history of either operation or trauma existed for this patient.
      Moreover, the location of the mass was unusual and the enhancement patterns of
      the dynamic magnetic resonance images were similar to that of a malignant tumor.
      Based on the radiologic findings, a surgical exploration was performed. A well
      circumscribed mass, which measured 3.2 x 2 cm, was found in the rectus muscle.
      Microscopic findings showed a typical zonal pattern with a fibroblastic central
      zone and a zone of ossification at the periphery. Although abdominal myositis
      ossificans is extremely rare, it is one of the causes of abdominal mass lesions
      and can be mistaken for a malignant tumor. Therefore, a thorough knowledge of the
      evolution of myositis ossificans is necessary and in cases with malignant
      suggestion on magnetic resonance imaging, like that seen in our case, we suggest
      that a surgical excision may be necessary for both the diagnosis and treatment.

PMID- 16794798
TI  - Endovascular repair of an abdominal aortic aneurysm in a patient with horseshoe
      kidney: report of a case.
AB  - A horseshoe kidney poses special problems during treatment of an abdominal aortic
      aneurysm (AAA), and there is much controversy about the most suitable method of
      repair. We report the case of a 65-year-old man with a horseshoe kidney, in whom
      an AAA was treated with a unibody bifurcated endograft. During the procedure, the
      two anomalous renal arteries were sacrificed. Although there was transient
      elevation of the creatinine levels, the patient was discharged with normal renal
      function and no endoleak from the accessory renal arteries. Thus, when two normal
      and two accessory renal arteries arise from the non-aneurysmatic proximal aortic
      neck, providing that preoperative kidney function is normal, it seems that the
      treatment can be safely carried out using an endovascular technique and excluding
      the accessory renal arteries. This case supports the feasibility of endovascular
      surgery for the treatment of AAA in the presence of a horseshoe kidney.

PMID- 16794799
TI  - Primary leiomyoma of the liver: report of a case.
AB  - We report a case of primary leiomyoma of the liver. A 71-year-old man was
      admitted for investigation of a mass lesion in his liver, detected on
      ultrasonography. Computed tomography (CT) showed a solid tumor, 3 cm in diameter,
      in the caudate lobe of the liver. He underwent partial hepatectomy, and
      histological findings of the resected specimen revealed the proliferation of
      spindle cells, which formed a pattern of interlacing bundles, without any
      evidence of malignancy. The tumor cells were not immunoreactive to c-kit or S
      100, but they were immunoreactive to alpha-smooth muscle actin. No other lesion
      was found elsewhere in the body. Thus, the tumor was diagnosed as a primary
      leiomyoma of the liver.

PMID- 16794800
TI  - An icteric type hepatocellular carcinoma with no detectable tumor in the liver:
      report of a case.
AB  - A 70-year-old man was admitted to our hospital with obstructive jaundice.
      Computed tomography revealed a tumor in the left intrahepatic bile duct extending
      to the common bile duct without any significant lesions in the liver.
      Cholangiography showed a filling defect due to an intraductal tumor. Cytology of
      the bile juice was negative and tumor markers were carcinoembryonic antigen 5.7
      ng/ml, carbohydrate antigen 19-9 49 U/ml, alpha-fetoprotein 9 ng/dl, and PIVKA-II
      19 200 AU/ml. With a preoperative diagnosis of hilar bile duct carcinoma, a
      laparotomy was performed. The common bile duct was filled with a tumor and it
      extended into the bilateral intrahepatic bile ducts. The intraductal tumor was
      removed together with the extrahepatic bile ducts. An intraoperative histological
      examination of the tumor showed a well-differentiated hepatocellular carcinoma.
      No lesions were detected in the liver by ultrasonography, palpation during the
      operation, or a computed tomography scan after the operation. At 1 year
      postoperatively, no recurrence has been seen in this patient.

PMID- 16794801
TI  - Intrahepatic segmental primary sclerosing cholangitis: report of a case.
AB  - A 67-year-old woman was referred to our hospital for investigation of epigastric
      discomfort. Computed tomography (CT) showed dilatation of the intrahepatic bile
      duct in the left lobe of the liver, endoscopic cholangiography showed complete
      stenosis of the left main branch of intrahepatic bile duct, and CT during
      angiography showed decreased portal blood flow to segment 3 of the liver. Based
      on these findings, we suspected intrahepatic cholangiocarcinoma and performed
      left lobectomy of the liver. However, pathological examination revealed fibrosis
      and infiltration of inflammatory lymphoid cells around the stenotic bile duct and
      periportal area, without any evidence of malignancy. Since these findings were
      compatible with sclerosing cholangitis and the patient did not have a disorder
      that would cause secondary sclerosing cholangitis, the final diagnosis was
      primary sclerosing cholangitis (PSC). It is difficult to distinguish segmental
      PSC from cholangiocarcinoma; thus we think surgical resection is an appropriate
      therapeutic and diagnostic procedure for segmental intrahepatic bile duct
      stenosis.

PMID- 16794802
TI  - Simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone
      independent macronodular adrenal hyerplasia: report of a case.
AB  - Cushing's syndrome caused by adrenocorticotropic hormone (ACTH)-independent
      macronodular adrenal hyperplasia (AIMAH) is an extremely rare disease, which
      shows bilateral macronodular adrenal hypertrophy and autonomous cortisol
      production. We herein report a case of AIMAH treated successfully by minimally
      invasive simultaneous bilateral laparoscopic adrenalectomy. A 73-year-old woman
      with hypertension, diabetes mellitus, and osteoporosis was referred to our
      hospital because of an incidentally found huge bilateral adrenal mass. An
      abdominal computed tomography scan showed large bilateral adrenal glands with
      multiple nodules. A diagnosis of AIMAH was made and a simultaneous bilateral
      laparoscopic adrenalectomy was thus performed. The total operation time was 310
      min and blood loss was 70 g. Both glands were hypertrophic (right 5 x 3 cm, 48.5
      g and left 4 x 2 cm, 39.2 g) and consisted of multiple golden yellow
      macronodules. The postoperative course was uneventful. A simultaneous bilateral
      adrenalectomy for AIMAH performed by an experienced surgical team is therefore
      considered to be a safe and minimally invasive procedure.

PMID- 16794803
TI  - Hyaline vascular-type Castleman's disease in the hepatoduodenal ligament: report
      of a case.
AB  - Castleman's disease is an uncommon lymphoproliferative disorder, which occurs
      most commonly in the mediastinum. Sporadic reports of its occurrence in the
      hepatoduodenal ligament and other extrathoracic locations have also been
      documented. Ultimately, Castleman's disease can develop anywhere lymphoid tissue
      is found, and the preoperative diagnosis is often difficult. We report a case of
      hyaline vascular-type Castleman's disease in the hepatoduodenal ligament. An
      asymptomatic 26-year-old woman was admitted to our hospital for further
      examination of a mass found on ultrasonography. A contrast-enhanced computed
      tomography scan confirmed a hypervascular mass in the hepatoduodenal ligament,
      and angiography showed that the mass was receiving its blood supply from various
      arteries. These findings suggested a diagnosis of Castleman's disease and we
      removed the tumor without resecting any other organs. Computed tomography and
      angiography were helpful in establishing a correct preoperative diagnosis, which
      minimized the magnitude of surgery.

PMID- 16794804
TI  - Left-sided paraduodenal hernia: report of a case.
AB  - Paraduodenal hernias are rare congenital malformations consisting of incomplete
      rotation of the midgut, which may lead to intestinal obstruction or simply be
      detected as an incidental finding at autopsy or laparotomy. We report a case of
      left paraduodenal hernia diagnosed preoperatively by computed tomography and
      operated on in an emergency setting for signs of peritoneal irritation. A
      misdiagnosis had been made when the patient suffered his first attack 6 months
      earlier and he had been treated for familial Mediterranean fever. We reduced the
      small bowel loops from the left paraduodenal hernia sac with ligation and
      transection of the inferior mesenteric vessels. The patient was discharged from
      hospital on postoperative day 4 after an uneventful recovery.

PMID- 16794805
TI  - Iliac lymph node metastasis of an unknown primary tumor: report of a case.
AB  - Metastasis to the lymph nodes around the iliac vessels from cancer of an unknown
      primary (CUP) tumor has not yet been reported in either the English or Japanese
      literature and it is therefore described herein for the first time. The patient
      was a 70-year-old woman with persistent right leg edema. Computed tomography (CT)
      displayed a mass around the iliac vessels while physical, laboratory, and other
      imaging examination did not show any other tumor. Preoperatively diagnosed as a
      retroperitoneal tumor, the patient underwent a tumor resection, but a
      histopathological examination revealed the tumor to be poorly differentiated
      squamous cell carcinoma. Only residual lymph nodes in the pelvis were detected by
      postoperative fluorine-18 fluorodeoxyglucose-positron emission tomography.
      Neither a primary lesion nor any signs of recurrence were demonstrated for 13
      months after radiotherapy for the residual nodes. We herein discuss the
      diagnosis, treatment, and follow-up of this less common CUP.

PMID- 16794806
TI  - Small bowel angiodysplasia associated with von Willebrand's disease: report of a
      case.
AB  - The association between angiodysplasia (AD) and von Willebrand's disease (vWD)
      was first described by Quick in 1967. The clinical course of patients with vWD
      and AD is characterized by multiple admissions to hospital for gastrointestinal
      bleeding, necessitating transfusions of packed red cells, factor VIII, and von
      Willebrand factor concentrates. The therapeutic management of these patients is
      difficult. Both medical and endoscopic techniques have been tried, but no
      treatment modality has been completely successful. We describe the clinical
      course of a patient affected by vWD, who suffered repeated massive
      gastrointestinal bleeding caused by small bowel AD. Intestinal resection was the
      only effective treatment, resulting in complete remission of the gastrointestinal
      bleeding.

PMID- 16794807
TI  - Synchronous adenocarcinomas of the ileum and transverse colon detected by capsule
      endoscopy: report of a case.
AB  - A 77-year-old woman was admitted to our hospital with anemia and anorexia.
      Neither gastrointestinal endoscopy nor computed tomography showed by abnormal
      findings; however, a capsule endoscopy, performed to detect obscure
      gastrointestinal bleeding, revealed a tumor in the ileum. When we tried to take
      biopsies of the ileal tumor by push enteroscopy via the anus, we found another
      tumor in the transverse colon. On exploration, tumors were identified in the
      ileum and the transverse colon. Thus, we resected the ileum and transverse colon
      with regional lymph node dissection. Histologic sections from both the ileum and
      colon revealed moderately differentiated adenocarcinomas with no lymph node
      metastasis.

PMID- 16794808
TI  - Anal canal carcinoma with Pagetoid spread: report of a case.
AB  - A 70-year-old man with a history of colon polyps was found to have a
      semipedunculated polyp in the anal canal. The patient was asymptomatic. The
      lesion was 14 mm in diameter and located 5 mm from the dentate line. Histological
      examination of biopsy specimens revealed well-differentiated adenocarcinoma of
      the anal canal. During transanal local excision of the tumor, an abnormality of
      the perianal skin was recognized. Although intraoperative frozen section of the
      perianal skin did not show malignancy, permanent sections of the perineal skin
      revealed Paget's cells in the epidermis. Pathological examination of the anal
      canal carcinoma revealed submucosally invasive well-differentiated adenocarcinoma
      with a positive distal surgical margin. Thus, we performed additional wide local
      excision of the perianal skin including the distal margin of the previous local
      excision. Pathological examination revealed continuance within the epidermis
      between the anal canal adenocarcinoma and Paget's cells in the perianal skin
      lesion. Scattered Paget's cells also formed some glandular structures. Thus, we
      concluded that the perianal skin lesion was Pagetoid spread of anal canal
      adenocarcinoma. This report shows that the perianal skin should be examined
      carefully in patients with anal canal carcinoma.

PMID- 16794809
TI  - Pseudotumoral appearance of a ruptured epidermal cyst in the foot.
AB  - We present a case of keratin granuloma due to a ruptured epidermal cyst,
      occurring in the foot, in a 52-year-old woman. The patient presented with a
      history of a slow-growing lump in the web space of the foot that had been present
      for over a year. Imaging appearances suggested a soft tissue neoplasm. Clinical
      presentation, radiological features and histopathological findings are described,
      and the relevant literature is reviewed.

PMID- 16794810
TI  - Insights into amprenavir resistance in E35D HIV-1 protease mutation from
      molecular dynamics and binding free-energy calculations.
AB  - Drug resistance is a very important factor contributing to the failure of current
      HIV therapies. The ability to understand the resistance mechanism of HIV-protease
      mutants may be useful in developing more effective and longer lasting treatment
      regimens. In this paper, we report the first computational study of the
      clinically relevant E35D mutation of HIV-1 protease in its unbound conformation
      and complexed with the clinical inhibitor amprenavir and a sample substrate (Thr
      Ile-Met-Met-Gln-Arg). Our data, collected from 10 ns molecular-dynamics
      simulations, show that the E35D mutation results in an increased flexibility of
      the flaps, thereby affecting the conformational equilibrium between the closed
      and semi-open conformations of the free protease. The E35D mutation also causes a
      significant reduction of the calculated binding free energies both for substrate
      and amprenavir, thus giving a plausible explanation for its ability to increase
      the level of resistance. One possible explanation for the emergence of this
      mutation, despite its unfavorable effect on substrate affinity, might be the role
      of E35D as an escape mutation, which favors escape from the immune system in
      addition to conferring drug resistance.

PMID- 16794811
TI  - The clinical significance of quality of life assessments in oncology: a summary
      for clinicians.
AB  - BACKGROUND: A series of six manuscripts with an introduction appeared in the Mayo
      Clinic Proceedings, based upon the collective effort of 30 individuals with an
      interest and expertise in assessing the clinical significance of quality of life
      (QOL) assessments. The series of manuscripts described the state of the science
      of QOL assessments in oncology clinical research and practice and included
      extensive literature and theoretical justification for the continued inclusion of
      QOL in oncology clinical research and practice. OBJECTIVES: The purpose of this
      paper is to produce a summary of these articles and to supplement these works
      with additional information that was gleaned from subsequent meetings and
      discussions of this material. The primary aim of this paper is to present a
      cogent and concise description for clinicians to facilitate the incorporation of
      QOL assessments into oncology clinical research and practice. The theoretical
      discussion is supplemented with an example of how the various ideas can be
      operationalized in an oncology clinical trial.

PMID- 16794812
TI  - Acute mastoiditis in infants.
AB  - We present a retrospective study of 37 infants who were operated for acute
      mastoiditis during the period 2000-2004 in Mother and Child Health Care
      Institute, Belgrade, Serbia and Montenegro. About 23 patients (62.2%) were male
      and 14 (37.8%) were female. Acute mastoiditis developed just after the first
      infection of the middle ear in 26 patients (70.3%). All patients had local and
      general symptoms. The most common local symptoms were blurred tympanic membrane
      in all patients, painful tenderness of mastoid in 21 (57%) and redness of
      tympanic membrane in 13 (36%). General signs of infection were loss of body
      weight in 28 (75.7%) patients, fever in 21 (56.8%), vomiting in 19 (51.3%),
      diarrhea in 19 (51.3%) and severe anemia that requested red blood cell
      transfusion in 6 (16.2%). Suppuration did not appear in any of the patients.
      Tympanocentesis had been performed prior to surgery in all patients. The most
      frequently isolated causative microorganism was Streptococcus pneumoniae which
      was found in 12 (32.5%) patients, Staphylococcus aureus was found in 8 (21.5%)
      and Hemophilus influenzae in 2 (5.5%). In 15 (405%) patients there was no
      bacterial isolation. Eleven patients (29.7%) who had previously had acute otitis
      media were implanted ventilation tubes during the surgical intervention. All
      patients were treated with antibiotics prior and after the surgical intervention.
      The finding on mastoidectomy was positive in all cases. According to the results
      of our study the combination of antibiotic and surgical treatment is optimal in
      treating acute mastoiditis. Making a diagnosis of acute mastoiditis might not be
      easy since there are no specific symptoms. We emphasize that it should always be
      considered as a differential diagnosis in cases of prolonged acute otitis media
      with no improvement after 10 days of antibiotic treatment, especially when
      accompanied with weight loss and general condition worsening.

PMID- 16794813
TI  - Cobalt(II)-selective membrane sensor based on a [Me2(13)dieneN4] macrocyclic
      cobalt complex.
AB  - A new poly(vinyl chloride)-based membrane was fabricated with the cobalt(II)
      complex of 2,4-dimethyl-1,5,8,11-tetraazacyclotrideca-1,4-diene [Me2(13)dieneN4]
      as an ion carrier. The membrane composition was Co2+ complex/PVC/NaTPB/DBP
      15:50:15:20 (w/w). The sensor exhibited a Nernstian response for Co2+ ions over a
      wide concentration range (7.94x10(-6)-1.0x10(-1) M) at pH 2.5-7.0, a response
      time of 10 s, and it could be used for 3 months without any significant
      divergence in potential. The proposed membrane sensor exhibited good selectivity
      for Co2+ over a wide variety of other metal ions and in mixtures containing up to
      25% (v/v) non-aqueous content. The sensor was successfully used as an indicator
      electrode in the potentiometric titration of Co2+ with EDTA and the direct
      determination of Co2+ in real samples.

PMID- 16794814
TI  - Evaluation of extraction/digestion techniques used to determine lead isotopic
      composition in forest soils.
AB  - Lead isotopic studies in soils provide an efficient tool for tracing the sources
      of lead pollution. Five different extraction/digestion techniques (0.05 M EDTA,
      0.5 M HNO(3), 2 M HNO3, aqua regia, total digestion) were used for lead isotopic
      composition (206Pb/207Pb) determination in three forest soil profiles with
      different kinds of prevailing Pb contamination (unpolluted area, smelting area
      and vicinity of a motorway). The results obtained showed that all
      extraction/digestion methods used for the determination of 206Pb/207Pb ratios in
      surface horizons containing high organic matter contents gave statistically
      identical values (according to the Tukey test). In mineral soil horizons,
      differences between the individual extraction/digestion methods could be observed
      (the lowest 206Pb/207Pb ratios were obtained from EDTA extracts, corresponding to
      weakly bound anthropogenic lead, and the highest 206Pb/207Pb ratios were obtained
      from total digestion). The combination of total digestion and EDTA extraction
      (labile lead fraction) seems to be the optimal combination for 206Pb/207Pb ratio
      determination and optimal result interpretation.

PMID- 16794815
TI  - Determination of ceruloplasmin in human serum by SEC-ICPMS.
AB  - This paper describes an analytical method for the determination of ceruloplasmin
      (Cp) in human serum. The method uses immunoaffinity chromatography and size
      exclusion chromatography (SEC) to "purify" the serum sample prior to analysis of
      63Cu and 65Cu by inductively-coupled plasma mass spectrometry (ICPMS). By
      removing the six most abundant proteins from serum with immunoaffinity
      chromatography and by using SEC to separate Cu bound by Cp from any free Cu that
      might be present in the serum sample, we demonstrated that SEC-ICPMS can
      accurately and reproducibly measure Cp in the ERM DA470 reference serum. Cp
      identification is based on retention time match of the unknown in the serum
      sample with the Cp external standard and the presence of 63Cu and 65Cu at a ratio
      of 2.2+/-0.1. This method was used to analyze a reference serum certified for Cp,
      47 serum samples from four different diseases and a set of normal controls. The
      reference serum and a serum sample from a patient with myocardial infarction, as
      well as a Cp standard, were also analyzed by electrospray mass spectrometry to
      confirm the presence of Cp in the SEC fraction known to contain 63Cu.

PMID- 16794817
TI  - Chemical monitoring and occurrence of alkylphenols, alkylphenol ethoxylates,
      alcohol ethoxylates, phthalates and benzothiazoles in sewage treatment plants and
      receiving waters along the Ter River basin (Catalonia, N. E. Spain).
AB  - This study presents a quantitative estimation of the analysis and fate of several
      emerging pollutants, some of them endocrine-disrupting compounds, in surface
      water samples collected at several locations along the Ter River and two of its
      tributaries. Influent and effluent waters and particulate matter from five sewage
      treatment plants (STP) that discharge into these rivers were also studied. The
      target compounds analyzed were: nonylphenol ethoxylates (NPEO), nonylphenol (NP),
      octylphenol (OP), bisphenol A (BPA), phthalates, alcohol ethoxylates (AEO) and
      benzothiazoles. Chemical analysis by liquid chromatography-mass spectrometry
      using an electrospray interface (LC-ESI-MS) revealed the presence of low amounts
      (between 0.06 and 17.5 microg L(-1)) of the target compounds NPE(1+2)O and NP,
      which were detected in 100% and 84% of the samples respectively. Maximum
      concentrations occurred in the STPs associated with the municipalities of Vic and
      Girona. From the fate and behavior data obtained for the various compounds
      analyzed in the STP influent and effluent, we can conclude that the STPs are
      effective at removing large amounts (more than 70%) of the compounds studied from
      the water.

PMID- 16794816
TI  - Advances in analytical techniques for polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans and dioxin-like PCBs.
AB  - Analytical techniques for the determination of polychorinated dibenzo-p-dioxins
      (PCDD), polychlorinated dibenzofurans (PCDF) and dioxin-like PCBs (DLPCB) are
      reviewed. The focus of the review is on recent advances in methodology and
      analytical procedures. The paper also reviews toxicology, the development of
      toxic equivalent factors (TEF) and the determination of toxic equivalent quantity
      (TEQ) values. Sources, occurrence and temporal trends of PCDD/PCDF are summarized
      to provide examples of levels and concentration ranges for the methods and
      techniques reviewed.

PMID- 16794818
TI  - GFR is better estimated by considering both serum cystatin C and creatinine
      levels.
AB  - Serum cystatin C (cysC) is a potential marker of the glomerular filtration rate
      (GFR) that has generated conflicting reports in children. A prospective study was
      conducted to assess the benefit of considering cysC together with serum
      creatinine (SCr) and demographic and morphologic characteristics to better
      estimate the 51Cr-ethylenediaminetetraacetate (EDTA) clearance (CL), i.e., the
      GFR. Plasma 51Cr-EDTA data from 100 children or young adults (range: 1.4-22.8
      years old) were analyzed according to the population pharmacokinetic approach by
      using the nonlinear mixed effects model (NONMEM) program. The actual CL was
      compared to the CL predicted according to different covariate equations. The best
      covariate equation (+/-95% confidence interval) was: GFR (ml/min)=63.2(+/-3.4) .
      [(SCr (microM)/96)(-0.35 (+/-0.20))] . [(cysC (mg/l)/1.2)(-0.56 (+/-0.19))] .
      [(body weight (kg)/45)(0.30 (+/-0.17))] . [age (years)/14)(0.40 (+/-0.16))]. This
      equation was associated with a less biased and more precise estimation than the
      Schwartz equation. CysC improves the estimation of the GFR in children if
      considered with other covariates within the mathematical formula.

PMID- 16794819
TI  - The salmonid MHC class I: more ancient loci uncovered.
AB  - An unprecedented level of sequence diversity has been maintained in the salmonid
      major histocompatibility complex (MHC) class I UBA gene, with between lineage AA
      sequence identities as low as 34%. The derivation of deep allelic lineages may
      have occurred through interlocus exon shuffling or convergence of ancient loci
      with the UBA locus, but until recently, no such ancient loci were uncovered.
      Herein, we document the existence of eight additional MHC class I loci in salmon
      (UCA, UDA, UEA, UFA, UGA, UHA, ULA, and ZE), six of which share exon 2 and 3
      lineages with UBA, and three of which have not been described elsewhere. Half of
      the UBA exon 2 lineages and all UBA exon 3 lineages are shared with other loci.
      Two loci, UGA and UEA, share only a single exon lineage with UBA, likely
      generated through exon shuffling. Based on sequence homologies, we hypothesize
      that most exchanges and duplications occurred before or during tetraploidization
      (50 to 100 Ma). Novel loci that share no relationship with other salmonid loci
      are also identified (UHA and ZE). Each locus is evaluated for its potential to
      function as a class Ia gene based on gene expression, conserved residues and
      polymorphism. UBA is the only locus that can indisputably be classified as a
      class Ia gene, although three of the eight loci (ZE, UCA, and ULA) conform in
      three out of four measures. We hypothesize that these additional loci are in
      varying states of degradation to class Ib genes.

PMID- 16794821
TI  - Putting 'clear' into nuclear medicine: a decade of PET/CT development.

PMID- 16794820
TI  - Phenotypic characterization of Bbs4 null mice reveals age-dependent penetrance
      and variable expressivity.
AB  - Bardet-Biedl syndrome (BBS) is a rare oligogenic disorder exhibiting both
      clinical and genetic heterogeneity. Although the BBS phenotype is variable both
      between and within families, the syndrome is characterized by the hallmarks of
      developmental and learning difficulties, post-axial polydactylia, obesity,
      hypogenitalism, renal abnormalities, retinal dystrophy, and several less
      frequently observed features. Eleven genes mutated in BBS patients have been
      identified, and more are expected to exist, since about 20-30% of all families
      cannot be explained by the known loci. To investigate the etiopathogenesis of
      BBS, we created a mouse null for one of the murine homologues, Bbs4, to assess
      the contribution of one gene to the pleiotropic murine Bbs phenotype. Bbs4 null
      mice, although initially runted compared to their littermates, ultimately become
      obese in a gender-dependent manner, females earlier and with more severity than
      males. Blood chemistry tests indicated abnormal lipid profiles, signs of liver
      dysfunction, and elevated insulin and leptin levels reminiscent of metabolic
      syndrome. As in patients with BBS, we found age-dependent retinal dystrophy.
      Behavioral assessment revealed that mutant mice displayed more anxiety-related
      responses and reduced social dominance. We noted the rare occurrence of birth
      defects, including neural tube defects and hydrometrocolpos, in the null mice.
      Evaluations of these null mice have uncovered phenotypic features with age
      dependent penetrance and variable expressivity, partially recapitulating the
      human BBS phenotype.

PMID- 16794822
TI  - Expression of serotonergic receptors in psoriatic skin.
AB  - Psoriasis appears to be influenced by stress, which causes release of adrenal
      hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors,
      may have a role in psoriasis. Distribution of serotonin receptors was studied in
      involved and noninvolved skin in patients with psoriasis and compared to normal
      skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3
      receptors (R). There was a decreased (P<0.001) number of 5-HT1AR positive cells,
      the majority being tryptase positive, in involved and noninvolved psoriatic
      papillary dermis, compared to normal skin. 5-HTlAR expression was also found in
      the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR
      expressing papillary mononuclear cells, CD3 positive, were increased (P<0.001 and
      P<0.01, respectively) in involved and noninvolved psoriatic skin, compared to
      normal skin, an increase (P<0.01) also being found in the involved compared to
      noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal
      layer of noninvolved but not in the involved skin of psoriasis, where it was only
      found in the acrosyringium. The present findings are compatible with the 5-HT1A
      and 5-HT2A receptors having antagonistic functions, and raise the possibility of
      using receptor specific drugs in the treatment of psoriasis.

PMID- 16794824
TI  - Meniscus transplantation.

PMID- 16794823
TI  - [Therapy of acute mayocardial infarction: COMMIT (Clopidogrel and Metoprolol
      Infarction Trial)].

PMID- 16794825
TI  - Botticelli and the Babinski sign.

PMID- 16794826
TI  - Leaf senescence is delayed in tobacco plants expressing the maize knotted1 gene
      under the control of a wound-inducible promoter.
AB  - To extend the shelf life of freshly harvested vegetables and cut flowers, a maize
      homeobox gene Knotted1 (kn1) was placed under the control of a wound-inducible
      promoter win3.12 from hybrid poplar (Populus trichocarpa x P. deltoides) and
      introduced into tobacco plants (Nicotiana tabacum cv. Xanthi). Transgenic
      win3.12::kn1 plants were morphologically normal. A leaf-detachment assay
      demonstrated that senescence in win3.12::kn1 leaves could be delayed by at least
      2 weeks compared with wild type leaves. Furthermore, all leaves of win3.12::kn1
      shoots remained green and healthy 3 weeks after excision and incubation in water,
      while older leaves of control shoots senesced under the same conditions.
      Additionally, a number of adventitious roots produced at the cut ends of wild
      type shoots after a 3-week incubation, but much a less number of adventitious
      roots appeared in win3.12::kn1 shoots. The delay in senescence was also confirmed
      by a higher total chlorophyll (a + b) content in win3.12::kn1 leaves relative to
      that of the control plants. RT-PCR analysis showed that the kn1 transcript was
      detected in win3.12::kn1 leaves with wounding treatment, but otherwise was not
      observed in leaves of wild type and unwounded transgenic plants. The results
      presented here indicate that expression of kn1 gene driven by the wound-inducible
      promoter win3.12 is potentially useful to delay senescence of vegetable crops and
      commercial horticulture after harvest.

PMID- 16794827
TI  - PDGF and microvessel wall remodeling in adult rat lung: imaging PDGF-AA and PDGF
      Ralpha molecules in progenitor smooth muscle cells developing in experimental
      pulmonary hypertension.
AB  - Smooth muscle cells are mostly absent from the walls of microvessels in the adult
      lung but develop in large numbers as part of the pathology of human and
      experimental pulmonary hypertensions (PHs). We have previously shown, in an in
      vivo model of experimental PH, that mesenchymal (interstitial) fibroblasts and
      intermediate cells are the progenitors of these cells. Although smooth muscle
      cell development is a defining pathophysiological feature of human PH, little is
      known about the angiogenic signaling molecules responsible. Here, we report data
      for platelet-derived growth factor AA (PDGF-AA) and PDGF-Ralpha, two components
      of an important signaling pathway for fibroblast and myofibroblast proliferation
      and migration. Using antibodies linked to protein-A gold and high-resolution
      imaging techniques, we analyzed the expression of these molecules as smooth
      muscle cells developed from progenitor cell populations and in endothelial cells
      of the same microvessels. PDGF-AA was highly expressed by each cell type in
      control lung. As PH developed, the number of antigenic sites for PDGF-AA
      decreased with time. PDGF-Ralpha expression levels in the control lung were low,
      relative to the ligand, and fell in PH. These data show, for the first time, a
      marked phenotypic shift in expression levels of the PDGF-AA isoform and its
      receptor tyrosine kinase in the progenitor smooth muscle cells developing in the
      microvessels of the adult hypertensive lung.

PMID- 16794828
TI  - Expression of phosphorylated ERK1/2 and homeodomain protein CDX2 in
      cholangiocarcinoma.
AB  - PURPOSE: The extracellular signal-regulated kinase (ERK) 1/2 pathway plays
      important roles in the regulation of cell proliferation, differentiation and cell
      survival. The caudal-related homeobox protein CDX2 is essential for the
      development of the intestine, and is related to gastric and gallbladder cancers
      with the intestinal phenotype. However, the roles of ERK1/2 phosphorylation
      (pERK1/2) and CDX2 in cholangiocarcinogenesis remain unknown. METHODS: We
      investigated the expression of pERK1/2, CDX2 and MUC2 in Thai cholangiocarcinoma
      (CCA) specimens by means of immunohistochemical staining, and compared the
      expression of these proteins with clinicopathological factors. RESULTS: The
      pERK1/2 protein was expressed in 29 of 59 (49.2%) CCA cases. Interestingly, in
      tubular-type CCA, the frequency of pERK1/2 expression was associated with a
      higher grade of differentiation (P = 0.001). CDX2 expression was observed in 22
      of the 59 (37.3%) CCA cases, showed a relationship with MUC2 expression (P =
      0.001), and was much higher in papillary-type than tubular-type CCA (P = 0.002).
      CONCLUSION: These results imply that pERK1/2 may be important for the
      differentiation of tubular-type CCA, while CDX2 is related to the intestinal
      phenotype of papillary-type CCA.

PMID- 16794829
TI  - Chemotherapeutic agents enhance AAV2-mediated gene transfer into breast cancer
      cells promoting CD40 ligand-based immunotherapy.
AB  - PURPOSE: Supplementing conventional treatment with gene therapy to induce an
      immune response might be beneficial to cancer patients. In this study, we
      evaluated the efficiency of transduction of breast cancer cells with recombinant
      adeno-associated virus (rAAV) and effects of cytotoxic agents used in
      chemotherapy. Furthermore, the capacity of tumor cells expressing transgenic CD40
      ligand (CD40L) to stimulate dendritic cells was measured. METHODS: Breast cancer
      cell lines were infected with a rAAV encoding the enhanced green fluorescent
      protein (EGFP) or murine CD40L and transgene expression was analyzed by flow
      cytometry. Stimulation of isolated human dendritic cells by CD40L-expressing
      tumor cells was quantified by measuring secreted interleukin 12. RESULTS:
      Infection with an EGFP-encoding rAAV resulted in variable fractions (14-93%, mean
      42%) of transgene-expressing cells. Pre-incubation of MM 157, MM 231, and MCF7
      cells with epirubicin or carboplatin substantially increased AAV-mediated
      transgene expression. rAAV/CD40L was used to generate CD40L-transgenic tumor
      cells, which specifically activated immature dendritic cells, as confirmed by
      blocking with an antibody binding to CD40L. CONCLUSIONS: The efficiency of rAAV
      mediated gene transfer into breast cancer cells is significantly higher than
      previously reported and can be further enhanced by co-administration of
      chemotherapeutic agents. We also confirmed that breast cancer cells can activate
      human dendritic cells after infection with a CD40L-encoding rAAV.

PMID- 16794830
TI  - Larval settlement of the common Australian sea urchin Heliocidaris erythrogramma
      in response to bacteria from the surface of coralline algae.
AB  - Bacterial biofilms are increasingly seen as important for the successful
      settlement of marine invertebrate larvae. Here we tested the effects of biofilms
      on settlement of the sea urchin Heliocidaris erythrogramma. Larvae settled on
      many surfaces including various algal species, rocks, sand and shells. Settlement
      was reduced by autoclaving rocks and algae, and by treatment of algae with
      antibiotics. These results, and molecular and culture-based analyses, suggested
      that the bacterial community on plants was important for settlement. To test
      this, approximately 250 strains of bacteria were isolated from coralline algae,
      and larvae were exposed to single-strain biofilms. Many induced rates of
      settlement comparable to coralline algae. The genus Pseudoalteromonas dominated
      these highly inductive strains, with representatives from Vibrio, Shewanella,
      Photobacterium and Pseudomonas also responsible for a high settlement response.
      The settlement response to different bacteria was species specific, as low
      inducers were also dominated by species in the genera Pseudoalteromonas and
      Vibrio. We also, for the first time, assessed settlement of larvae in response to
      characterised, monospecific biofilms in the field. Larvae metamorphosed in higher
      numbers on an inducing biofilm, Pseudoalteromonas luteoviolacea, than on either a
      low-inducing biofilm, Pseudoalteromonas rubra, or an unfilmed control. We
      conclude that the bacterial community on the surface of coralline algae is
      important as a settlement cue for H. erythrogramma larvae. This study is also an
      example of the emerging integration of molecular microbiology and more
      traditional marine eukaryote ecology.

PMID- 16794831
TI  - Density-dependent regulation of population size in colonial breeders: Allee and
      buffer effects in the migratory Montagu's harrier.
AB  - Expanding populations offer an opportunity to uncover the processes driving
      spatial variation in distribution and abundance. Individual settlement decisions
      will be influenced by the availability and relative quality of patches, and by
      how these respond to changes in conspecific density. For example, conspecific
      presence can alter patch suitability through reductions in resource availability
      or territorial exclusion, leading to buffer effect patterns of disproportionate
      population expansion into poorer quality areas. However, conspecific presence can
      also enhance patch suitability through Allee effect processes, such as
      transmission of information about resources or improved predator detection and
      deterrence. Here, we explore the factors underlying the settlement pattern of a
      growing population of Montagu's harriers (Circus pygargus) in Spain. The
      population increased exponentially between 1981 and 2001, but stabilised between
      2001 and 2004. This population increase occurred alongside a remarkable spatial
      expansion, with novel site use occurring prior to maximum densities in occupied
      sites being reached. However, no temporal trends in fecundity were observed and,
      within sites, average fecundity did not decline with increasing density. Across
      the population, variance in productivity did increase with population size,
      suggesting a complex pattern of density-dependent costs and benefits. We suggest
      that both Allee and buffer effects are operating in this system, with the
      benefits of conspecific presence counteracting density-dependent declines in
      resource availability or quality.

PMID- 16794832
TI  - Hierarchical patch dynamics and animal movement pattern.
AB  - In hierarchical patch systems, small-scale patches of high density are nested
      within large-scale patches of low density. The organization of multiple-scale
      hierarchical systems makes non-random strategies for dispersal and movement
      particularly important. Here, we apply a new method based on first-passage time
      on the pathway of a foraging seabird, the Antarctic petrel (Thalassoica
      antarctica), to quantify its foraging pattern and the spatial dynamics of its
      foraging areas. Our results suggest that Antarctic petrels used a nested search
      strategy to track a highly dynamic hierarchical patch system where small-scale
      patches were congregated within patches at larger scales. The birds searched for
      large-scale patches by traveling fast and over long distances. Once within a
      large-scale patch, the birds concentrated their search to find smaller scale
      patches. By comparing the pathway of different birds we were able to quantify the
      spatial scale and turnover of their foraging areas. On the largest scale we found
      foraging areas with a characteristic scale of about 400 km. Nested within these
      areas we found foraging areas with a characteristic scale of about 100 km. The
      large-scale areas disappeared or moved within a time frame of weeks while the
      nested small-scale areas disappeared or moved within days. Antarctic krill
      (Euphausia superba) is the dominant food item of Antarctic petrels and we suggest
      that our findings reflect the spatial dynamics of krill in the area.

PMID- 16794833
TI  - Consequences of nitrogen and phosphorus limitation for the performance of two
      planthoppers with divergent life-history strategies.
AB  - Phytophagous insects have a much higher nitrogen and phosphorus content than
      their host plants, an elemental mismatch that places inherent constraints on
      meeting nutritional requirements. Although nitrogen limitation is well documented
      in insect herbivores, phosphorus limitation is poorly studied. Using factorial
      experiments in the laboratory and field, in which levels of soil nitrogen and
      phosphorus were manipulated, we studied the relative consequences of
      macronutrient limitation for two herbivores, namely the phloem-feeding
      planthoppers Prokelisia dolus and P. marginata. These planthoppers inhabit the
      salt marshes of North America where large stands of their Spartina host plant are
      found. Notably, these congeners differ in their dispersal abilities; P. marginata
      is dispersive whereas P. dolus is sedentary. Both nitrogen and phosphorus
      subsidies enhanced the nitrogen and phosphorus content of Spartina. When P. dolus
      and P. marginata were raised on plants with an enriched nitrogen signature, they
      exhibited greater survival, grew to a larger size, developed more rapidly, and
      achieved higher densities than on nitrogen-deficient plants. However, P.
      marginata experienced greater fitness penalties than P. dolus on nitrogen
      deficient plants. Phosphorus limitation and associated fitness penalties were not
      as severe as nitrogen limitation for P. marginata, and were not detected in P.
      dolus. The tempered response of P. dolus to N- and P-deficient Spartina is
      probably due to its greater investment in feeding musculature and hence ability
      to compensate for nutrient deficiencies with increased ingestion. To cope with
      deteriorating plant quality, P. dolus employs compensatory feeding, whereas P.
      marginata disperses to higher quality Spartina. When its option of dispersal is
      eliminated and P. marginata is confined on nutrient-deficient plants, its
      performance is drastically reduced compared with P. dolus. This research
      highlights the importance of interfacing herbivore life-history strategies with
      ecological stoichiometry in order to interpret the consequences of macronutrient
      limitation on herbivore performance and population dynamics.

PMID- 16794834
TI  - Dietary specialization in European species groups of seed beetles (Coleoptera:
      Bruchidae: Bruchinae).
AB  - Because of their particular biology, seed beetles exhibit a strong relationship
      with their larval host plants. In Europe, however, field data have long been
      scarce and unreliable. The results of Legume seed collections of nearly 1,000
      samples belonging to 292 species from various locations in Europe are summarized.
      The status of current Bruchidius species groups is amended on morphological and
      phylogenetic bases. Recent advances in the knowledge of phylogenetic structures
      of both Fabaceae and Bruchinae provide a new picture of Bruchinae-Fabaceae
      interactions. It reveals a certain level of host conservatism. The hypothesis of
      radiative adaptation seems the most compatible with observed data.

PMID- 16794835
TI  - A new perspective on size hierarchies in nature: patterns, causes, and
      consequences.
AB  - Many plant and animal aggregations have size hierarchies within which a variety
      of sizes of individuals, from large to small, can be found. Size hierarchies are
      thought to indicate the existence of competition amongst individuals within the
      aggregation, but determining their exact cause is difficult. The key to
      understanding size hierarchies lies in first quantifying the pattern of size and
      growth of individuals. We conducted a quantitative investigation of pattern in
      the size hierarchy of the clown anemonefish Amphiprion percula, in Madang Lagoon,
      Papua New Guinea. Here, groups of A. percula occupy sea anemones (Heteractis
      magnifica) that provide protection from predators. Within each anemone there is a
      single group composed of a breeding pair and zero to four non-breeders. Within
      each group there is a single size hierarchy; the female is largest (rank 1), the
      male is second largest (rank 2), and the non-breeders get progressively smaller
      (ranks 3-6). We demonstrate that individuals adjacent in rank are separated by
      body size ratios whose distribution is significantly different from the
      distribution expected under a null model-the growth of individuals is regulated
      such that each dominant ends up being about 1.26 times the size of its immediate
      subordinate. We show that it is decisions about growth at the individual level
      that generate the size hierarchy at the group level, and thereby determine
      maximum group size and population size. This study provides a new perspective on
      the pattern, causes and consequences of size hierarchies.

PMID- 16794836
TI  - A simple general method to evaluate intra-specific transpiration parameters
      within and among seedling families.
AB  - A method to evaluate the genetic control of plant response to increasing soil
      water deficit is proposed. A description of single tree transpiration behavior
      was obtained considering parameters independent from air and soil conditions. We
      removed environmental effects by using two approaches: the normalization of
      drought data to control (watered) plants and the fitting of a process model. We
      analyzed the transpiration of 475 4-year-old European beech seedlings, belonging
      to eight full-sib families. Approximately, one-third of the seedlings were kept
      in well-watered conditions while the others were exposed to drought for 14 days.
      Daily plant transpiration was estimated as the difference between two subsequent
      gravimetric measurements. A mechanistic model was fitted to transpiration data
      separately for each tree. In the model, the relationship of transpiration with
      vapor pressure deficit and soil water deficit of each tree is modulated by three
      parameters: maximum leaf conductance (gM1), maximum transpiration in well-watered
      soil conditions E(M0)1 and a parameter describing stomatal sensitivity to soil
      water deficit (c). The model successfully fitted most single tree data and a
      distribution of estimates for the three parameters (gM1, E(M0)1 and c) was
      obtained. Predicted transpiration values were in good agreement with observed
      data (R (2) = 0.86). The model approach produced parameters significantly
      correlated with those of the "normalization to control" approach. Estimated
      parameters vary considerably among trees, suggesting the presence of individual
      differences in stomatal behavior and response to drought. In spite of a large
      among tree (within family) variation, the among families component for gM1,
      E(M0)1 and c explained 9.5, 3.3 and 0.1% of total parameters variation suggesting
      a significant genetic control of transpiration processes.

PMID- 16794837
TI  - Searching for the Holy Grail of the acute respiratory distress syndrome.

PMID- 16794838
TI  - Outcome value of Clara cell protein in serum of patients with acute respiratory
      distress syndrome.
AB  - OBJECTIVE: Injury to the alveolocapillary barrier characterizes ALI/ARDS;
      therefore determining levels of lung epithelium-specific small proteins in serum
      may help predict clinical outcomes. We examined whether serum Clara cell protein
      (CC-16) concentration is correlated with the outcome, mechanical ventilation
      duration, and incidence of nonpulmonary organ failure. DESIGN: Prospective
      multicenter observational study conducted by the Quebec Critical Care Network.
      MEASUREMENTS: Seventy-eight adult ARDS patients requiring mechanical ventilation
      were enrolled and 28-day mortality was the primary outcome. Ventilatory
      parameters were computed and blood was sampled daily. Clinical information
      collected included cause of death, duration of mechanical ventilation, number of
      ventilator-free days, and organ failures. RESULTS: Median serum levels of CC-16
      were significantly higher in nonsurvivors than survivors on days 0-2 (19.93
      microg/l, IQR 11.8-44.32, vs. 8.9, 5.66-26.38) and sustained up to day 14. CC-16
      levels were correlated positively with the number of failing organs (rho 0.3623)
      and requirement for prolonged mechanical ventilation. Predictors of patient
      mortality included age, arterial carbon dioxide partial pressure, CC-16, and
      APACHE II score (odds ratios 1.35, 1.52, 1.37, 1.159, respectively). CONCLUSIONS:
      Higher initial CC-16 serum level is associated with increased risk of death,
      fewer ventilator-free days, and increased frequency of nonpulmonary multiple
      organ failure. CC-16 is a valuable biomarker of ARDS that may help predict
      outcome among ARDS patients with high-risk mortality.

PMID- 16794839
TI  - Varied growth, biomass and cellulose content in tobacco expressing yeast-derived
      invertases.
AB  - The effects of the expression of yeast-derived apoplastic (AI) and cytosolic (CI)
      invertases (EC 3.2.1.26) on biomass and structural carbohydrate accumulation in
      tobacco (Nicotiana tabacum L. cv. Xanthi) were evaluated. Transgenic tobacco
      plants expressing AI or CI under the control of either a tandem repeat of the
      Cauliflower Mosaic Virus 35S promoter (2X35S), or a promoter that drives xylem
      localized expression (Petroselinum crispum 4-coumarate:CoA ligase promoter; 4CL)
      were generated. Yeast-derived invertase transcript levels, invertase protein,
      enzyme activity, growth parameters as well as both structural and soluble
      carbohydrates of stem tissue of all transformed lines were quantified. Transgenic
      tobacco lines expressing invertase under the control of 4CL displayed severe
      growth retardation with both yeast-derived isogenes. Similarly, several
      transformed lines expressing either AI or CI regulated by the 2X35S promoter were
      also shorter than wild-type (WT) plants. Despite the decreases in height, some
      transformed lines had significant increases in biomass. One line (2X35S::AI-1)
      had a biomass/height increase of 88% and an increase in stem diameter of over
      40%, while a second line (2X35S::CI-5) had a biomass/height increase of 21%. A
      separate line (2X35S::AI-2) had a 36% increase in cellulose content, while two
      others (4CL::AI-2 and 4CL::AI-3) displayed significant decreases in cellulose
      content. The observed phenotypes can be in part explained by the levels of
      foreign invertase present, subcellular localization and the carbohydrate status
      of the tissues.

PMID- 16794840
TI  - Pinoresinol-lariciresinol reductase gene expression and secoisolariciresinol
      diglucoside accumulation in developing flax (Linum usitatissimum) seeds.
AB  - The transcription activity of the pinoresinol-lariciresinol reductase (PLR) gene
      of Linum usitatissimum (so-called LuPLR), a key gene in lignan synthesis, was
      studied by RT-PCR and promoter-reporter transgenesis. The promoter was found to
      drive transcription of a GUSint reporter gene in the seed coats during the flax
      seed development. This fitted well with the tissue localization monitored by semi
      quantitative RT-PCR of LuPLR expression. Accumulation of the main flax lignan
      secoisolariciresinol diglucoside was coherent with LuPLR expression during seed
      development. This three-way approach demonstrated that the LuPLR gene is
      expressed in the seed coat of flax seeds, and that the synthesis of PLR enzyme
      occurs where flax main lignan is found stored in mature seeds, confirming its
      involvement in SDG synthesis.

PMID- 16794842
TI  - The perineuronal glial tissue of spinal ganglia. Quantitative changes in the
      rabbit from youth to extremely advanced age.
AB  - The volumes of the nerve cell bodies and those of the enveloping satellite cell
      sheaths from spinal ganglia were determined by morphometric methods applied to
      electron micrographs in young, adult, old and very old rabbits. The mean volume
      of the nerve cell bodies increased progressively with age; this is probably
      related to the increase with age of the body size of the rabbits studied. The
      mean volume of the satellite cell sheaths did not differ significantly in young,
      adult and old animals, but was significantly smaller in very old animals. It is
      extremely unlikely that this marked reduction in the volume of the satellite cell
      sheath is the result of a pathological process. The mean value of the volume
      ratio between the satellite cell sheaths and the related nerve cell bodies did
      not differ significantly in young and adult animals, but was significantly
      smaller in old and very old animals. This ratio was particularly low in very old
      animals. Our analysis showed that in each age group the volume of the satellite
      cell sheath is linearly related to the volume of the related nerve cell body.
      This result suggests that in rabbit spinal ganglia the quantitative relations
      between glial and nervous tissue are tightly controlled throughout life. It is
      suggested that ganglionic neurons release signals to influence and control the
      volume of their associated glial tissue. Since satellite cells have important
      support roles for the neurons they surround, it is likely that the marked
      reduction in the volume of perineuronal sheaths in the extremely advanced age is
      accompanied by a reduction of those roles, with negative consequences for
      neuronal activity.

PMID- 16794841
TI  - Gametophytic self-incompatibility: understanding the cellular mechanisms involved
      in "self" pollen tube inhibition.
AB  - Self-incompatibility (SI) prevents the production of "self" seed and inbreeding
      by providing a recognition and rejection system for "self," or genetically
      identical, pollen. Studies of gametophytic SI (GSI) species at a molecular level
      have identified two completely different S-genes and SI mechanisms. One GSI
      mechanism, which is found in the Solanaceae, Rosaceae and Scrophulariaceae, has S
      RNase as the pistil S-component and an F-box protein as the pollen S-component.
      However, non-S-locus factors are also required. In an incompatible situation, the
      S-RNases degrade pollen RNA, thereby preventing pollen tube growth. Here, in the
      light of recent evidence, we examine alternative models for how compatible pollen
      escapes this cytotoxic activity. The other GSI mechanism, so far found only in
      the Papaveraceae, has a small secreted peptide, the S-protein, as its pistil S
      component. The pollen S-component remains elusive, but it is thought to be a
      transmembrane receptor, as interaction of the S-protein with incompatible pollen
      triggers a signaling network, resulting in rapid actin depolymerization and
      pollen tube inhibition and programmed cell death (PCD). Here, we present an
      overview of what is currently known about the mechanisms involved in regulating
      pollen tube inhibition in these two GSI systems.

PMID- 16794843
TI  - Early-onset osteoporosis with high bone turnover in children with Morquio
      Brailsford syndrome.

PMID- 16794844
TI  - Neurological involvement in North Italian patients with Behcet disease.
AB  - The aim of this study was to evaluate neurological involvement in a series of 110
      North Italian patients with Behcet disease (BD), a multisystemic vasculitis of
      unknown origin, followed up for a period of 5 years. During this time, 27 (24.5%)
      patients with neuro-BD were identified. Twenty out of 27 showed at least one
      acute attack in their clinical course. In 14 of them, a neurological evaluation
      was carried out during the attack. The other 13 patients were evaluated during a
      remission phase. The onset of neuro-BD was usually characterized by an acute
      attack with motor symptoms (66.6%) and behavioural/cognitive changes (47.6%),
      while headache was more frequent in the remission phase (76.9%). On magnetic
      resonance imaging, large brain-stem/diencephalon lesions were usually seen during
      the attack. In the remission phase, they were often located in the white-matter.
      Aspecific cerebrospinal fluid abnormalities were usually seen during the attacks.
      Cerebrospinal fluid analysis together with radiological and clinical features
      seems to be useful for the differential diagnosis in these patients.

PMID- 16794845
TI  - [Reduction of arthrosis associated knee pain through a single intra-articular
      injection of synthetic hyaluronic acid].
AB  - AIM: Conventional hyaluronic acids need three to five injections for therapeutic
      success, whereas Durolane), a synthetic hyaluronic acid, needs only a single
      injection. Clinical outcome using Durolane should be compared with the results of
      studies using hyaluronic acids or glucocorticoids. METHOD: Fifty patients with
      primary gonarthrosis stages I-III (Kellgren Score) were investigated for knee
      function, pain intensity, and quality of life. The knee and osteoarthritis
      outcome score (KOOS), visual analogue scale (VAS), and European quality of live
      score (EQ-5D), as well as motion of the knee were measured. Patients were
      investigated before, and 2, and 24 weeks after injection. RESULTS: Two weeks
      after injection, the subjective function of knee and quality of life had
      increased significantly. In the following 22 weeks, all parameters increased
      significantly (quality of life and activity +19%; range of motion active 109 vs.
      115 degrees ; pain, 55 vs. 41 mm (VAS); all p<0.01). CONCLUSION: We conclude that
      a single injection of Durolane can reduce arthrosis associated knee pain
      sufficiently. Our data are comparable with those published in clinical studies
      using other hyaluronic acids. The effects of Durolane are delayed but more
      sustained compared than those found for glucocorticoids. Because of the single
      injection, we see an advantage in using Durolane compared to other conventional
      hyaluronic acids and glucocorticoids.

PMID- 16794846
TI  - Role of the right dorsal premotor cortex in "physiological" mirror EMG activity.
AB  - A distributed cortical network enables the lateralization of intended unimanual
      movements, i.e., the transformation from a default mirror movement to a unimanual
      movement. Little is known about the exact functional organization of this "non
      mirror transformation" network. Involvement of the right dorsal premotor cortex
      (dPMC) was suggested because its virtual lesion by high-frequency repetitive
      transcranial magnetic stimulation (rTMS) increased the excitability of the left
      primary motor cortex (M1) during unilateral isometric contraction of a left hand
      muscle (Cincotta et al., Neurosci Lett 367: 189-93, 2004). However, no
      behavioural effects were observed in that experimental protocol. Here we tested
      behaviourally twelve healthy volunteers to find out whether focal disruption of
      the right dPMC by "off-line" One Hz rTMS (900 pulses, 115% of resting motor
      threshold) enhances "physiological" mirroring. This was measured by an
      established protocol (Mayston et al., Ann Neurol 45: 583-94, 1999) that
      quantifies the mirror increase in the electromyographic (EMG) level in the
      isometrically contracting abductor pollicis brevis (APB) muscle of one hand
      during brief phasic contractions performed with the APB of the other hand.
      Mirroring in the right APB significantly increased after real rTMS of the right
      dPMC. In contrast, no change in mirroring was seen with sham rTMS of the right
      dPMC, real rTMS of the right M1, or real rTMS of the left dPMC. These findings
      strongly support the hypothesis that the right dPMC is part of the non-mirror
      transformation cortical network.

PMID- 16794847
TI  - How active gaze informs the hand in sequential pointing movements.
AB  - Visual information is vital for fast and accurate hand movements. It has been
      demonstrated that allowing free eye movements results in greater accuracy than
      when the eyes maintain centrally fixed. Three explanations as to why free gaze
      improves accuracy are: shifting gaze to a target allows visual feedback in
      guiding the hand to the target (feedback loop), shifting gaze generates ocular
      proprioception which can be used to update a movement (feedback-feedforward), or
      efference copy could be used to direct hand movements (feedforward). In this
      experiment we used a double-step task and manipulated the utility of ocular
      proprioceptive feedback from eye to head position by removing the second target
      during the saccade. We confirm the advantage of free gaze for sequential
      movements with a double-step pointing task and document eye-hand lead times of
      approximately 200 ms for both initial movements and secondary movements. The
      observation that participants move gaze well ahead of the current hand target
      dismisses foveal feedback as a major contribution. We argue for a feedforward
      model based on eye movement efference as the major factor in enabling accurate
      hand movements. The results with the double-step target task also suggest the
      need for some buffering of efference and ocular-proprioceptive signals to cope
      with the situation where the eye has moved to a location ahead of the current
      target for the hand movement. We estimate that this buffer period may range
      between 120 and 200 ms without significant impact on hand movement accuracy.

PMID- 16794848
TI  - Bilateral basal ganglia activation associated with sensorimotor adaptation.
AB  - Sensorimotor adaptation tasks can be classified into two types. When subjects
      adapt movements to visual feedback perturbations such as in prism lens
      adaptation, they perform kinematic adaptations. When subjects adapt movements to
      force field perturbations such as with robotic manipulanda, they perform kinetic
      adaptations. Neuroimaging studies have shown basal ganglia involvement in kinetic
      adaptations, but have found little evidence of basal ganglia involvement in
      kinematic adaptations, despite reports of deficits in patients with diseases of
      the basal ganglia, such as Parkinson's and Huntington's disease, in these. In an
      effort to resolve such apparent discrepancy, we used FMRI to focus on the first
      few minutes of practice during kinematic adaptation. Human subjects adapted to
      visuomotor rotations in the context of a joystick aiming task while lying supine
      in a 3.0 T MRI scanner. As demonstrated previously, early adaptive processes were
      associated with BOLD activation in the cerebellum and the sensory and motor
      cortical regions. A novel finding of this study was bilateral basal ganglia
      activation. This suggests that, at least for early learning, the neural
      correlates of kinematic adaptation parallel those of other types of skill
      learning. We observed activation in the right globus pallidus and putamen, along
      with the right prefrontal, premotor and parietal cortex, which may support
      spatial cognitive processes of adaptation. We also observed activation in the
      left globus pallidus and caudate nucleus, along with the left premotor and
      supplementary motor cortex, which may support the sensorimotor processes of
      adaptation. These results are the first to demonstrate a clear involvement of
      basal ganglia activation in this type of kinematic motor adaptation.

PMID- 16794849
TI  - Thermotropic phase behavior of DPPC liposome systems in the presence of the anti
      cancer agent 'Ellipticine'.
AB  - This letter presents our first results on the structural changes in DPPC
      multilamellar vesicles dispersed in water in the presence of the anti-cancer
      agent Ellipticine. The thermotropic phase transitions of the lamellar packing
      inside lipid vesicles were characterized in situ by small angle X ray
      diffraction. The results lead to the determination of a critical concentration
      value for drug loading on the vesicle system around 4% molar fraction of
      Ellipticine, an indication of the localization of the drug in the alkyl chains
      and the influence of the drug on the decreasing rate of the bilayer period after
      the main phase transition.

PMID- 16794850
TI  - [Diagnostic strategies in cases of suspected periprosthetic infection of the
      knee. A review of the literature and current recommendations].
AB  - Reliable confirmation of periprosthetic infection after total knee arthroplasty
      is a diagnostic challenge. The present work reviews published data evaluating the
      available diagnostic tools. Erythrocyte sedimentation rate and C-reactive protein
      serum levels are relatively sensitive methods with rather low specificity towards
      periprosthetic infection and are mainly applied to exclude infection. Studies
      evaluating scintigraphic methods--especially white cell scans--provide
      inconsistent data with varying accuracy. Consequently, white cell scans cannot be
      recommended as standard methods. Immunoscintigraphy with antigranulocyte
      antibodies and FDG-PET scans demonstrated promising results with particularly
      high sensitivities, but have to be validated in larger studies. Microbiological
      evaluation of joint aspirates proved high specificity for periprosthetic
      infection. However, an average of 20% of infected cases remained undetected.
      Nevertheless, aspiration is widely recommended for preoperative isolation of the
      infecting organism. Intraoperative frozen sections demonstrated excellent
      specificity with good sensitivity. The real accuracy of intraoperative culture
      and permanent histology cannot be determined due to the missing golden standard;
      however, a combination of both methods is recommended to define the final
      diagnosis. Large studies validating both methods and criteria for the final
      diagnosis of periprosthetic infection are necessary to optimize the diagnostic
      algorithm.

PMID- 16794851
TI  - How fish do geometry in large and in small spaces.
AB  - It has been shown that children and non-human animals seem to integrate geometric
      and featural information to different extents in order to reorient themselves in
      environments of different spatial scales. We trained fish (redtail splitfins,
      Xenotoca eiseni) to reorient to find a corner in a rectangular tank with a
      distinctive featural cue (a blue wall). Then we tested fish after displacement of
      the feature on another adjacent wall. In the large enclosure, fish chose the two
      corners with the feature, and also tended to choose among them the one that
      maintained the correct arrangement of the featural cue with respect to geometric
      sense (i.e. left-right position). In contrast, in the small enclosure, fish chose
      both the two corners with the features and the corner, without any feature, that
      maintained the correct metric arrangement of the walls with respect to geometric
      sense. Possible reasons for species differences in the use of geometric and non
      geometric information are discussed.

PMID- 16794852
TI  - Orientation in the cuttlefish Sepia officinalis: response versus place learning.
AB  - Several studies have demonstrated that mammals, birds and fish use comparable
      spatial learning strategies. Unfortunately, except in insects, few studies have
      investigated spatial learning mechanisms in invertebrates. Our study aimed to
      identify the strategies used by cuttlefish (Sepia officinalis) to solve a spatial
      task commonly used with vertebrates. A new spatial learning procedure using a T
      maze was designed. In this maze, the cuttlefish learned how to enter a dark and
      sandy compartment. A preliminary test confirmed that individual cuttlefish showed
      an untrained side-turning preference (preference for turning right or left) in
      the T-maze. This preference could be reliably detected in a single probe trial.
      In the following two experiments, each individual was trained to enter the
      compartment opposite to its side-turning preference. In Experiment 1, distal
      visual cues were provided around the maze. In Experiment 2, the T-maze was
      surrounded by curtains and two proximal visual cues were provided above the
      apparatus. In both experiments, after acquisition, strategies used by cuttlefish
      to orient in the T-maze were tested by creating a conflict between the formerly
      rewarded algorithmic behaviour (turn, response learning) and the visual cues
      identifying the goal (place learning). Most cuttlefish relied on response
      learning in Experiment 1; the two strategies were used equally often in
      Experiment 2. In these experiments, the salience of cues provided during the
      experiment determined whether cuttlefish used response or place learning to solve
      this spatial task. Our study demonstrates for the first time the presence of
      multiple spatial strategies in cuttlefish that appear to closely parallel those
      described in vertebrates.

PMID- 16794853
TI  - Reservosomes: multipurpose organelles?
AB  - Reservosomes are endocytic organelles from Trypanosoma cruzi epimastigotes that
      store proteins and lipids for future use. The lack of molecular markers for the
      compartments of this parasite makes it difficult to clarify all reservosome
      functions, as they present characteristics of pre-lysosomes, lysosomes and
      recycling compartments.

PMID- 16794854
TI  - Treatment with dehydroepiandrosterone (DHEA) stimulates oxidative energy
      metabolism in the liver mitochondria from developing rats.
AB  - Effects of treatment with DHEA (0.2 mg or 1.0 mg / kg body weight for 7 days) on
      oxidative energy metabolism on liver mitochondria from developing and young adult
      rats were examined. Treatment with DHEA resulted in a progressive dose-dependent
      increase in the liver weights of the developing animals without change in the
      body weight. In the young adult rats treatment with 1.0 mg DHEA showed increase
      only in the body weight. Treatment with DHEA stimulated state 3 and state 4
      respiration rates in developing as well as young adult rats in dose-dependent
      manner with all the substrates used; magnitude of stimulation was age-dependent.
      In young adults the extent of simulation of state 3 respiration rates declined at
      higher dose (1.0 mg) of DHEA with glutamate and succinate as substrates.
      Stimulation of state 3 respiration rates was accompanied by increase in contents
      of cytochrome aa3, b and c + c1 and stimulation of ATPase and dehydrogenases
      activities in dose- and age-dependent manner.

PMID- 16794855
TI  - Decreased creatine kinase activity caused by electroconvulsive shock.
AB  - Although several advances have occurred over the past 20 years concerning the use
      and administration of electroconvulsive therapy to minimize side effects of this
      treatment, little progress has been made in understanding its mechanism of
      action. Creatine kinase is a crucial enzyme for brain energy homeostasis, and a
      decrease of its activity has been associated with neuronal death. This work was
      performed in order to evaluate creatine kinase activity from rat brain after
      acute and chronic electroconvulsive shock. Results showed an inhibition of
      creatine kinase activity in hippocampus, striatum and cortex, after acute and
      chronic electroconvulsive shock. Our findings demonstrated that creatine kinase
      activity is altered by electroconvulsive shock.

PMID- 16794856
TI  - Region-specific interrelations between apoptotic proteins expression and DNA
      fragmentation in the neonatal rat brain.
AB  - DNA fragmentation, mRNA and protein levels of Bcl-XL, Bax and caspase-3 were
      determined to characterize interrelations between expression of these apoptotic
      markers in the neonatal brain regions. High DNA fragmentation intensity in the
      cortex was in consonance with the lowest Bcl-XL/Bax expression ratio, the highest
      procaspase-3 and active caspase-3 levels. Low and intermediate DNA fragmentation
      levels in the cerebellum and hippocampus respectively were also in a good
      agreement with apoptotic proteins expression in these structures. In the cortex,
      hippocampus and cerebellum DNA fragmentation intensity was proportional to the
      active caspase-3 level. In contrast to these structures, in the brainstem, the
      lowest level of this protease was accompanied by the highest intensity of DNA
      fragmentation among the brain regions studied. The data suggest that cell death
      normally occurring during early postnatal life could be realized in the
      developing brainstem via caspase-3-independent pathways in animals that express
      this protease.

PMID- 16794857
TI  - Modification of morphine-induced hyperlocomotion and antinociception in mice by
      clorgyline, a monoamine oxidase-A inhibitor.
AB  - We evaluated the effects of pretreatment with clorgyline, an irreversible
      monoamine oxidase (MAO)-A inhibitor, on morphine-induced hyperlocomotion and
      antinociception. A single administration of morphine (30 mg/kg, i.p.) to male ICR
      mice induced a hyperlocomotion. ANOVA analysis revealed the statistical
      significance of the morphine effect on horizontal locomotion and of the
      clorgyline pretreatment x morphine interaction effect, but not of the effect of
      clorgyline pretreatment. The initial (5 min after challenge) phase of morphine
      actions vs. saline challenge appeared as if morphine had a strong inhibitory
      effect on locomotor activity in combination with different doses of clorgyline.
      The mice administered with morphine in combination of clorgyline (1 and 10 mg/kg)
      did not show any stereotypic behaviors. Clorgyline at a dose of 0.1 mg/kg but not
      other doses tested significantly potentiated morphine-induced antinociception
      evaluated by tail flick but not hot plate test. During the measurements of
      locomotor activity and antinociception, clorgyline at doses of 1 and 10 mg/kg
      significantly inhibited monoamine metabolism through MAO. These results suggest
      that clorgyline showed an inhibitory effect on morphine-induced hyperlocomotion,
      but not antinociception, through MAO inhibition. There is not a possibility that
      clorgyline pretreatment enhanced morphine action on motor activity, resulting in
      the abnormal behavior from hyperlocomotion to stereotypic movements.

PMID- 16794858
TI  - Effect of ischemic neuronal insults on amyloid precursor protein processing.
AB  - The nature of the association between ischemic stroke and Alzheimer's disease
      (AD) at the cellular and molecular level is still unknown. We evaluated the
      effect of ischemic neuronal insults on the regulation of amyloid precursor
      protein (APP) processing. We used an in vitro model of cerebral ischemia (oxygen
      glucose deprivation) to evaluate the effect of ischemic neuronal insults on the
      amyloidogenic and non-amyloidogenic pathways using human neuroblastoma cell line
      and primary cultured cells of transgenic mice which expressed human APP (Tg2576).
      Ischemic neuronal insults increased the production of Abeta in Tg2576 primary
      culture cells compared to controls. A disintegrin and metalloprotease 10 (ADAM
      10) was markedly increased in early stage of ischemic insults, which was followed
      by decreased level of ADAM 10 expression in later stage. The protein and mRNA
      expression of beta-site cleavage enzyme (BACE) and BACE activity was not
      significantly different between the group of ischemic insults and control. By
      contrast, the activity of gamma-secretase was significantly increased after 4 h
      of ischemic insults, as compared to controls. The present study showed that the
      ischemic neuronal insults increased the production of Abeta by influencing APP
      metabolism, which may link the role of ischemic insults to the pathogenesis of
      AD.

PMID- 16794859
TI  - High glutamate decreases S100B secretion by a mechanism dependent on the
      glutamate transporter.
AB  - Several molecules have been shown to be involved in glial-neuronal communication,
      including S100B, an astrocyte-derived neurotrophic cytokine. Extracellular S100B
      protects hippocampal neurons from excitotoxic damage, whilst toxic levels of
      glutamate to neurons have been shown to reduce S100B secretion in astrocytes and
      brain slices, by an unknown mechanism. Here, we investigate which mechanisms are
      possibly involved in this effect in primary cultures of hippocampal astrocytes
      using glutamate agonists and glutamate uptake inhibitors. DCG-IV, an agonist of
      group II metabotropic glutamate receptors, caused a smaller decrease in S100B
      secretion when compared to 1 mM glutamate. D: -aspartate partially reverted the
      glutamate effect on S100B release and two other inhibitors, PDC and DIDS,
      reverted it completely. These findings suggest that S100B secretion is inversely
      coupled to glutamate uptake. Decrease in S100B secretion may be considered as
      direct excitotoxic damage, but a beneficial mechanism effect cannot be ruled out,
      because S100B elevation could cause an additional cell death.

PMID- 16794860
TI  - H2O2 mobilizes Ca2+ from agonist- and thapsigargin-sensitive and insensitive
      intracellular stores and stimulates glutamate secretion in rat hippocampal
      astrocytes.
AB  - The effect of hydrogen peroxide (H2O2) on cytosolic free calcium concentration
      ([Ca2+]c) as well as its effect on glutamate secretion in rat hippocampal
      astrocytes have been the aim of the present research. Our results show that 100
      microM H2O2 induces an increase in [Ca2+]c, that remains at an elevated level
      while the oxidant is present in the perfusion medium, due to its release from
      intracellular stores as it was observed in the absence of extracellular Ca2+,
      followed by a significant increase in glutamate secretion. Ca2+-mobilization in
      response to the oxidant could only be reduced by thapsigargin plus FCCP,
      indicating that the Ca2+-mobilizable pool by H2O2 includes both endoplasmic
      reticulum and mitochondria. We conclude that ROS in hippocampal astrocytes might
      contribute to an elevation of resting [Ca2+]c which, in turn, could lead to a
      maintained secretion of the excitatory neurotransmitter glutamate, which has been
      considered a situation potentially leading to neurotoxicity in the hippocampus.

PMID- 16794861
TI  - Neuroprotective effect of etomidate in the central nervous system of
      streptozotocin-induced diabetic rats.
AB  - It is well known that hyperglycaemia due to diabetes mellitus leads to oxidative
      stress in the central nervous system. Oxidative stress plays important role in
      the pathogenesis of neurodegenerative changes. In the present study we
      investigated the possible neuroprotective effect of etomidate against
      streptozotocin-induced (STZ-induced) hyperglycaemia in the rat brain and spinal
      cord. A total of 40 rats were used in this study. Rats were divided into four
      groups: sham-control, diabetic, diabetic-etomidate treated and vehicle for
      etomidate treatment group. Diabetes mellitus was induced by a single injection of
      streptozotocin (60 mg/kg body weight). Three days after streptozotocin injection,
      etomidate (2 mg/kg) was injected intraperitoneally for etomidate group and lipid
      emulsion (10%) for vehicle group was injected with corresponding amount
      intraperitoneally every day for 6 weeks. Six weeks after streptozotocin
      injection, seven rats from each group were killed and brain, brain stem and
      cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain
      stem and spinal cord were dissected for the biochemical analysis (the level of
      malondialdehyde [MDA], total nitrite, reduced glutathione [GSH], and xanthine
      oxidase [XO] activity). STZ-induced diabetes resulted in significantly elevation
      of MDA, XO and nitrite levels in the hippocampus, cortex, cerebellum, brain stem
      and spinal cord of the rats (P < 0.05) while etomidate treatment provided
      significantly lower values (P < 0.05). This study demonstrated that etomidate
      have neuroprotective effect on the neuronal tissue against the diabetic oxidative
      damage.

PMID- 16794862
TI  - Evaluation of the neuroprotective effects of citicoline after experimental spinal
      cord injury: improved behavioral and neuroanatomical recovery.
AB  - Spinal cord injury (SCI) caused by trauma mainly occurs in two mechanisms as
      primary and secondary injury. Secondary injury following the primary impact
      includes various pathophysiological and biochemical events. Methylprednisolone is
      the only pharmacological agent having clinically proven beneficial effects on
      SCI. Citicoline has been shown to have clinical and experimental beneficial
      effects on brain ischemia. This study aims to investigate the neuroprotective
      effect of citicoline in an experimental SCI model in rats. Sixty adult Wistar
      albino rats were randomized into five groups. SCI was performed by the weight
      drop model. Group 1 underwent laminectomy alone. The Group 2 underwent
      laminectomy followed by SCI and received no medication. Group3, Group 4 and Group
      5 underwent laminectomy followed by SCI and received medication. Group 3 and
      Group 5 received citicoline and Group 4 and Group 5 received methylprednisolone.
      The rats were divided into two subgroups for biochemical analysis (sacrificed at
      24 h after surgery) and neurobehavioral and histopathological evaluation
      (sacrificed at 6 weeks after surgery). Malondialdehyde levels, nitric oxide
      levels and trauma size ratios were lower and reduced glutathione levels were
      higher in Group 3, Group 4 and Group 5 as compared to Group 2. Posttraumatic
      neurological recovery after surgery was significantly better in Group 3, Group 4
      and Group 5 compared to Group 2. In conclusion, this study demonstrates that
      citicoline is as effective as methylprednisolone. The efficacy of citicoline
      combined with methylprednisolone is not superior to either citicoline or
      methylprednisolone alone.

PMID- 16794863
TI  - Statistical validation of two sample comparison methods for oligonucleotide
      microarray in rat ischemia model.
AB  - In gene expression analyses using a high-density oligonucleotide array in a rat
      ischemia model, two comparison methods, "pair-wise comparison" and "sample
      average comparison", were evaluated based on statistical methods. The reliability
      of the elements screened with a 1.2 to 10-fold threshold was also evaluated. In
      pair-wise comparisons, most of the elements were significantly independent of the
      threshold value, with the percentage of significant elements remaining above 95%,
      when screened at 2.5-fold or higher threshold value. Pair-wise comparison
      structurally provided strict screening, which resulted in genes that were not
      selected despite significant alterations in expression. Screening by "sample
      average comparison" resulted in elements with low probability of significance,
      which suggested the necessity for increasing the reliability by additional
      statistical analyses after screening. When genes with altered expression were
      screened using an oligonucleotide array, marked differences in the numbers and
      reliability were proved to exist among elements screened by each sample
      comparison method.

PMID- 16794864
TI  - Agonist-induced internalization of the Caenorhabditis elegans muscarinic
      acetylcholine receptor GAR-3 in Chinese hamster ovary cells.
AB  - Many membrane-bound neurotransmitter receptors are known to be internalized by
      exposure to agonist. This agonist-induced receptor internalization is considered
      to play important roles in receptor-mediated signaling. Here we investigated the
      internalization of GAR-3, a Caenorhabditis elegans muscarinic acetylcholine
      receptor, using cultured mammalian cells. When Chinese hamster ovary cells stably
      expressing GAR-3 were treated with carbachol, GAR-3 was internalized in a dose-
      and time-dependent manner. Approximately 60% of the cell surface receptor was
      internalized by exposure to 1 mM carbachol for 1 h. Carbachol-induced GAR-3
      internalization was suppressed by treatment with hypertonic sucrose, which blocks
      the formation of clathrin-coated pits. Overexpression of a dominant-negative
      dynamin mutant (DynK44A), but not of a dominant-negative beta-arrestin mutant
      (Arr319-418), substantially inhibited carbachol-induced internalization of GAR-3.
      Thus, these data suggest that GAR-3 undergoes agonist-induced internalization via
      a clathrin- and dynamin-dependent but beta-arrestin-independent pathway.
      Depletion of Ca2+ by simultaneous treatment of the cells with BAPTA/AM (Ca2+
      mobilization blocker) and EGTA (Ca2+ influx blocker) almost completely blocked
      agonist-induced GAR-3 internalization. Moreover, treatment of the cells with the
      Ca2+ ionophore A23187 led to GAR-3 internalization in the absence of agonist.
      These results indicate that Ca2+ plays a critical role in GAR-3 internalization.
      We tested whether the third intracellular (i3) loop of GAR-3 is involved in
      agonist-stimulated receptor internalization. A GAR-3 deletion mutant lacking a
      large central portion of the i3 loop exhibited an internalization pattern
      comparable to that of the wild type, suggesting that the central i3 loop is not
      required for the internalization of GAR-3.

PMID- 16794865
TI  - Assessing defense structure in school-age children using the Response Evaluation
      Measure-71-Youth version (REM-Y-71).
AB  - This study used the Response Evaluation Measure-Youth (REM-Y-71), a self-report
      measure of 21 defense reactions, among school-age children. Participants were
      elementary and middle school students (n = 290; grades 3-8; age range: 8-15; mean
      = 11.73). Factor analysis revealed a 2-factor defense structure consistent with
      structure among high school and adult samples. The composite REM-Y defense scores
      for each factor were significant predictors of social desirability, using the
      Children's Defensiveness Scale (CDS); anxiety, using the State-Trait Anxiety
      Inventory for Children (STAIC); and psychosocial functioning. This study
      represents the first cross-sectional empirical analysis of overall defense
      structure and use among children and early adolescents.

PMID- 16794866
TI  - Consumption and metabolism of 1,2-dimethoxy-4-(3-fluoro-2-propenyl)benzene, a
      fluorine analog of methyl eugenol, in the oriental fruit fly Bactrocera dorsalis
      (Hendel).
AB  - Methyl eugenol (ME) is a natural phenylpropanoid highly attractive to oriental
      fruit fly Bactrocera dorsalis (Hendel) males. The flies eagerly feed on ME and
      produce hydroxylated metabolites with both pheromonal and allomonal functions.
      Side-chain metabolic activation of ME has long been recognized as a primary
      reason for hepatocarcinogenicity of this compound on rodents. In an attempt to
      develop a safer alternative to ME for fruit fly management, we developed a
      fluorine analog 1,2-dimethoxy-4-(3-fluoro-2-propenyl)benzene (I), which, in
      earlier field tests, was as active to the oriental fruit fly as ME. Now we report
      that B. dorsalis males are not only attracted to, but also eagerly consume (up to
      approximately 1 mg/insect) compound I, thus recognizing this fluorinated benzene
      as a close kin of the natural ME. The flies metabolized the fluorine analog I in
      a similar fashion producing mostly two hydroxylated products, 2-(3-fluoro-2
      propenyl)-4,5-dimethoxyphenol (II) and (E)-coniferyl alcohol (III), which they
      stored in rectal glands. However, the introduction of the fluorine atom at the
      terminal carbon atom of the double bond favors the ring hydroxylation over a side
      chain metabolic oxidation pathway, by which coniferyl alcohol is produced. It
      also appears that fluorination overall impedes the metabolism: at high feed rate
      (10 mul per 10 males), the flies consumed in total more fluorine analog I than ME
      but were unable to metabolize it as efficiently as ME.

PMID- 16794867
TI  - A batch chemiluminescence determination of enoxacin using a tris-(1,10
      phenanthroline)ruthenium(II)-cerium(IV) system.
AB  - A batch type chemiluminescence (CL) determination of enoxacin is described. In
      this work, it was observed that enoxacin could enhance the chemiluminescence (CL)
      emission Ru(phen)3(2+)-Ce(IV) system and this enhancement effect was dependent on
      the concentration of enoxacin, based on which, CL system was established for the
      determination of enoxacin. Under the optimum experimental conditions, the linear
      range and detection limit are 0.6406-64.06 microg/ml and 0.0210 microg/ml,
      respectively. The R.S.D. is 1.75%. (n = 10). The proposed method has been applied
      to detect the content of enoxacin in pharmaceutical formulation and human serum
      with satisfactory results. The possible mechanism of the CL reaction was
      discussed.

PMID- 16794868
TI  - Examining protein-lipid interactions in model systems with a new squarylium
      fluorescent dye.
AB  - The applicability of newly synthesized squarylium dye Sq to probing the changes
      in physical characteristics of lipid bilayer on the formation of protein-lipid
      complexes has been evaluated. Lipid vesicles composed of zwitterionic
      phospholipid phosphatidylcholine (PC) and its mixtures with positively charged
      detergent cetyltrimethylammonium bromide (CTAB), anionic phospholipid cardiolipin
      (CL), and cholesterol (Chol) were employed as lipid component of model membrane
      systems while protein constituent was represented by lysozyme (Lz). Fluorescence
      intensity of Sq was found to decrease on Lz association with lipid bilayer. This
      effect was observed in all kinds of model systems suggesting that Sq is sensitive
      to modification of lipid bilayer physical properties on hydrophobic protein-lipid
      interactions. It was found that Sq spectral response to variations in Chol
      content depends on relative contributions of electrostatic and hydrophobic
      components of Lz-membrane binding.

PMID- 16794869
TI  - Fluorescence resonance energy transfer and complex formation between thiazole
      orange and various dye-DNA conjugates: implications in signaling nucleic acid
      hybridization.
AB  - Fluorescence resonance energy transfer (FRET) was investigated between the
      intercalating dye thiazole orange (TO), and the dyes Cyanine 3 (Cy3), Cyanine 5
      (Cy5), Carboxytetramethyl Rhodamine (TAMRA), Iowa Black FQ (IabFQ), and Iowa
      Black RQ (IabRQ), which were covalently immobilized at the end of dsDNA
      oligonucleotides. In addition to determining that TO was an effective energy
      donor, FRET efficiency data obtained from fluorescence lifetime measurements
      indicated that TO intercalated near the middle of the 19mer oligonucleotide
      sequence that was used in this study. Discrepancies in FRET efficiencies obtained
      from intensity and lifetime measurements led to the investigation of non
      fluorescent complex formation between TAMRA and modified TO. The hydrophobicity
      of TO was modified by the addition of either an alkyl or polyethylene glycol
      (PEG) side-chain to study effects of dimer and aggregate formation. It was found
      that at stoichiometric excesses of modified TO, fluorescence quenching of TAMRA
      was observed, and that this could be correlated to the hydrophobicity of a TO
      chain species. The TAMRA:TO-chain association constant for the TO-alkyl system
      was 0.043+/-0.002 M(-1), while that obtained for the TO-PEG was 0.037+/-0.002 M(
      1). From the perspective of method development for the transduction of
      hybridization events, we present and evaluate a variety of schemes based on
      energy transfer between TO and an acceptor dye, and discuss the implications of
      complex formation in such schemes.

PMID- 16794870
TI  - Quenchers induce wavelength dependence on protein fluorescence lifetimes.
AB  - We have analysed the picosecond resolved fluorescence emission decay of
      horseradish peroxidase A2 and of HEW lysozyme acquired with a streak camera.
      Analyses of the fluorescence decay data of both proteins revealed that the
      dynamics of the decay is dependent on the emission wavelength. Our data strongly
      indicates that resonance energy transfer occurring between aromatic residues and
      different protein fluorescence quencher groups, and the nature of the quencher
      groups, are the causes of the observed wavelength dependent mean lifetime
      distribution. Using the global analysis data to calculate the fluorescence mean
      lifetime at each wavelength revealed that for lysozyme, the mean fluorescence
      lifetime increased with observation wavelength, whereas the opposite was the case
      for peroxidase. Both proteins contain strong fluorescence quencher groups located
      in close spatial proximity to the protein's aromatic residues. Lysozyme contains
      disulfide bridges as the main fluorescence quencher whereas peroxidase contains a
      heme group. Both for lysozyme and horseradish peroxidase there is a clear
      correlation between the observed fluorescence mean lifetime of the protein at a
      particular emission wavelength and the respective quencher's extinction
      coefficient at the respective wavelength. Furthermore, our study also reports a
      comparison of the analyses of the fluorescence data done with three different
      methods. Analyses of the fluorescence decay at 10 different fluorescence emission
      wavelengths revealed significant differences in both fluorescence lifetimes and
      the pre-exponential factor distributions. Such values differed from the values
      recovered from the integrated decay curves and from global analyse.

PMID- 16794871
TI  - Evidence of coordinate field index influence on upconversion properties in Er3+
      doped tellurite glasses.
AB  - Tellurite glasses doping the same concentration of Er3+ were prepared by
      conventional melting procedure, and their upconversion luminescences were
      measured. Two green emission bands at 521 nm and 550 nm and one red emission band
      at 657 nm were observed. This paper reported on the deduction of coordinate field
      index, which was proposed by deducing from Pauling's rules on the basis of
      Zachaiasen's random network theory, it was defined to the qualitative index that
      stand for the deviation of a given truly coordinate polyhedron from the
      hypothetical one. It can be used to rationalize the remarkable and regularity
      variation in the upconversion intensity in our prepared tellurite glasses.

PMID- 16794872
TI  - Fluorimetric study on molecular recognition of beta-cyclodextrin with 2-amino-9
      fluorenone.
AB  - The molecular recognition interaction of beta-cyclodextrin (beta-CDx) was
      investigated using 2-amino-9-fluorenone (2AFN) by UV, steady-state fluorescence
      and time-resolved fluorescence measurements in aqueous solution at various pH.
      The effect of acidity on the ground and excited state equilibria between the
      neutral and the monocationic forms of 2AFN in water and in beta-CDx environments
      are studied. Based on the change in the fluorescence spectrum and lifetimes of
      2AFN by the addition of beta-CDx, it is found that the unsubstituted part of the
      2AFN is encapsulated in the hydrophobic cavity of beta-CDx. The unusual red shift
      obtained for the protonation of amino group in water and beta-CDx solution is due
      to large solvent relaxation of the monocation. The structure of the 1:1 inclusion
      complex between 2AFN and beta-CDx has been proposed on the basis of ground and
      excited state pKa values and the bond distances obtained by MOPAC/AM 1 data.

PMID- 16794873
TI  - Monitoring pyrene excimers in lactose permease liposomes: revealing the presence
      of phosphatidylglycerol in proximity to an integral membrane protein.
AB  - In this study, we examined the annular lipid composition of the transmembrane
      protein lactose permease (LacY) from Escherichia coli. LacY was reconstituted
      into 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphoethanolamine (POPE) and 1-Palmitoyl
      2-Oleoyl-sn-Glycero-3-3-[Phospho-rac-(1-glycerol)] (POPG) and labeled with 1
      hexadecanoyl-2-(1-pyrenedecanoyl)-sn-Glycero-3-phosphoglycerol (PPDPG) at a
      3:0.99:0.01 molar ratio. Pyrene excimer formation was monitored by exciting a
      single tryptophan mutant of the protein (T320W). The results suggest that POPG
      remains segregated in the vicinity of the protein, most likely forming part of
      the annular composition. The possible involvement of POPG in hydrogen binding
      with the protein, as well as the molecular mechanism of LacY, is also discussed
      in the context of the proteomic network theory.

PMID- 16794874
TI  - Quantitative time-resolved fluorescence spectrum of the cortical sarcoma and the
      adjacent normal tissue.
AB  - The difference in time-resolved fluorescence spectrum between the cortical
      sarcoma and the adjacent normal tissue was studied in both experimental and
      theoretical ways. The Clinical data were obtained in vivo using a time-resolved
      fluorescence spectrometer employing a single fiber-optic probe for excitation and
      detection. Tissue was modeled as s-180 sarcoma tumor surrounded with normal
      muscle and was mediated by the Palladium-porphyrin photosensitizer (Pd-TCPP). The
      emitted fluorescence was considered as arising from the tumor tissue or the
      normal muscle, due to the presence of the photosensitizer. A computational code
      which could simulating time-resolved fluorescence emission was presented and
      applied to comparing fluorescence decay of photosensitizer in different stages of
      tumor growth. In this code the different stages of the tumor was modeled through
      changing the time tau, the delay of the fluorescence photon emission and z (max),
      the thickness of the tumor. It was found in the in vivo experiment that the
      fluorescence from tumor tissue decayed more quickly than from the adjacent normal
      muscle. For the ten rats in the first experiment day, the mean decay constant of
      tumor T (s) and normal tissue T (n) were 554 and 526 mus, respectively. And T (s)
      increased with the tumor growth, from 554 mus in the first day to 634 mus in the
      eighth day while T (s) kept steady. It was believed that the more adequate oxygen
      supplied by the normal tissue can more effectively quench the fluorescence and in
      the normal tissue the photosensitizer lifetime is smaller. As a result the
      simulated time-resolved fluorescence spectrum of normal tissue showed more
      quickly decay. And the thickness of the tumor can also delay the fluorescence
      decay. Both the experimental and simulated results indicated that the germination
      of the tumor would increase the decay constant of the time-resolved fluorescence
      spectrum. So decay constant of the tumor tissue spectrum should be larger than
      that of adjacent normal tissue for the reason of hypoxia and overgrowth. This
      fact could be of use in the tumor diagnoses.

PMID- 16794875
TI  - Interactive cell modeling web-resource, iCell, as a simulation-based teaching and
      learning tool to supplement electrophysiology education.
AB  - An interactive cell modeling web site, iCell
      (http://ssd1.bme.memphis.edu/icell/), that integrates research and education, was
      developed to present and to disseminate JAVA-coded models of cellular activities,
      and to supplement physiology education. iCell can be used to supplement the text
      book material as a simulation-based teaching and learning tool. Specifically,
      iCell allows the students to supplement their learning experiences of the text
      book cellular physiology material by running simulations in an interactive
      environment. The site consists of JAVA-coded models of various cardiac cells and
      neurons, and provides simulation data of their bioelectric transport activities
      at cellular level. Each JAVA-coded model allows the user to go through menu
      options to change model parameters, run and view simulation results. The site
      also has a glossary section for the scientific terms. iCell has been used as a
      teaching and learning tool for seven graduate courses at the Joint Biomedical
      Engineering Program of University of Memphis and University of Tennessee. This
      modeling tool was also used as a collaboration site among our physiology
      colleagues interested in simulations of cell membrane activities. Scientists from
      the fields of biosciences, engineering, life sciences and medical sciences in 17
      countries have tested and utilized iCell as a simulation-based teaching, learning
      and collaboration environment. iCell provides us with an interactive, platform
      independent, and user-friendly teaching and learning resource, and also a
      collaboration environment for electrophysiology to be shared over the Internet.
      The usage of simulations for teaching and learning will continue advancing
      simulation-based engineering and sciences for research and development.

PMID- 16794876
TI  - Integrating social science and design inquiry through interdisciplinary design
      charrettes: an approach to participatory community problem solving.
AB  - Interdisciplinary collaborations that aim to facilitate meaningful community
      outcomes require both the right mix of disciplinary knowledge and effective
      community participation, which together can deepen collective knowledge and the
      capacity to take action. This article explores three interdisciplinary design
      charrettes, intensive participatory workshops that addressed specific community
      problems and provided a context for integrating design and social science inquiry
      with local community knowledge. Evaluation data from the charrettes shed light on
      how students from the design and social science disciplines experienced the
      charrettes, and on their interactions with community members. Key advantages to
      this interdisciplinary, community-based collaboration included expanded knowledge
      derived from the use of multiple modes of inquiry, particularly the resulting
      visualization tools that helped community members understand local issues and
      envision novel solutions. Key drawbacks included difficulties in balancing the
      two disciplines, the tendency for social scientists to feel out of place on
      designers' turf, and the increased disciplinary and interpersonal conflicts
      arising from a more diverse pool of participants.

PMID- 16794877
TI  - Research reservations: response and responsibility in an American Indian
      community.
AB  - Community action research among the Assiniboine and Gros Ventre tribes of the
      Fort Belknap Indian reservation in Montana was undertaken to identify the
      cultural grounds for innovative mental health service delivery. As an enrolled
      tribal member investigating these matters in my "home" community, however, I
      encountered a series of challenges and limitations emerging from respondent
      reservations about sharing personal experiences of difficulty and distress, and
      the perceived means for redressing these. Focusing upon a difficult interview
      with a knowledgeable tribal elder, I enlist sociolinguistic analysis--the study
      of communicative norms governing who talks with whom about what (and under which
      conditions)--as one crucial means to making sense of this complex research
      encounter. Similar analyses would seem necessary to ensuring the cultural
      validity of research conclusions in cross-cultural action research more
      generally.

PMID- 16794879
TI  - [Nursing research].

PMID- 16794878
TI  - Executive function and the frontal lobes: a meta-analytic review.
AB  - Currently, there is debate among scholars regarding how to operationalize and
      measure executive functions. These functions generally are referred to as
      "supervisory" cognitive processes because they involve higher level organization
      and execution of complex thoughts and behavior. Although conceptualizations vary
      regarding what mental processes actually constitute the "executive function"
      construct, there has been a historical linkage of these "higher-level" processes
      with the frontal lobes. In fact, many investigators have used the term "frontal
      functions" synonymously with "executive functions" despite evidence that
      contradicts this synonymous usage. The current review provides a critical
      analysis of lesion and neuroimaging studies using three popular executive
      function measures (Wisconsin Card Sorting Test, Phonemic Verbal Fluency, and
      Stroop Color Word Interference Test) in order to examine the validity of the
      executive function construct in terms of its relation to activation and damage to
      the frontal lobes. Empirical lesion data are examined via meta-analysis
      procedures along with formula derivatives. Results reveal mixed evidence that
      does not support a one-to-one relationship between executive functions and
      frontal lobe activity. The paper concludes with a discussion of the implications
      of construing the validity of these neuropsychological tests in anatomical,
      rather than cognitive and behavioral, terms.

PMID- 16794880
TI  - [Optimizing the nursing process by new management instruments. The Northern
      Germany Nursing Research Network].
AB  - The Northern Germany Nursing Research Network (Pflegeforschungsverbund Nord) has
      dedicated itself to developing management instruments intended to optimize the
      nursing process. It is coordinated by the administrative office of the Institute
      of Public Health and Nursing Research (Institut fur Public Health und
      Pflegeforschung IPP, director: Prof. Dr. Stefan Gorres), Department of
      "Interdisziplinare Alterns- und Pflegeforschung", University of Bremen. Four
      partial projects are currently being worked on in two groups: Group A--"Deficient
      areas of nursing action": The projects belonging to this group are "Individual
      care-patterns of elderly people and their determinants" (University of Bremen)
      and "Mobility Restrictions in Nursing Homes-Multicentre Observational Study
      (MORIN)" (University of Hamburg). The purpose of these studies is to examine the
      relevance of quantitatively significant risk combinations from a nursing science
      perspective. Group B--"The generation and testing of nursing action management
      instruments": The projects in this area are "Nursing rounds as instruments of
      quality assurance in home-based care" (University of Applied Sciences, Bremen)
      and "Predicting the risk of falls, efficiency of standard scales in opposition to
      nursing assessment-Cluster-Randomised Controlled Trial (PROFESSION)" (University
      of Hamburg). These studies concentrate in a unique manner on the generation and
      testing of management/control instruments suitable for application to nursing
      action.

PMID- 16794881
TI  - [The need for autonomy in the process of care-conceptual framework and research
      perspectives].
AB  - The article reflects the difference between independence and self-determination
      or autonomy in care relations. We consider that independence is only a fiction
      even for people with no functional limitations. Compared with this are people in
      need of care always confronted with professional interventions in their daily
      life which limit their self-determination. Even if participation and therefore
      also autonomy are part of the goal setting process in care a hierarchy in the
      relation of professional nurses and client is hardly to neglect. Quality of care
      with methods of evidence based nursing has must always take into account the
      client's implicit knowledge and experience which we call the "internal" evidence.
      Only the respect of the internal evidence can reduce the structural hierarchy
      between nurse and client. The article exemplifies these general conditions in
      care with nurse-client communication and the challenges of quality of care and
      quality of life.

PMID- 16794882
TI  - [Persons with dementia in individual everyday situations. First results of an
      intervention study].
AB  - First outcomes of a current intervention study focussing on emotions of nursing
      home residents with mild, moderate and severe dementia are discussed in the
      present contribution. The aim of the study was to prove the effect from an
      individual approach in the care of people with dementia. By promoting individual
      everyday situations for each resident, positive emotions should be stimulated and
      individual well-being should be improved. Findings show the possibility to gain
      such individual everyday-situations for people with mild, moderate and severe
      dementia, which stimulate positive reactions and may be integrated into the care
      process. Of particular importance are those positive situations which focus on
      the communication between nurses and residents or in which the residents receive
      personal attention from nurses.

PMID- 16794883
TI  - [The importance of biographical approaches in nursing science].
AB  - Critical life events (e. g. disease, loss of be loved one) biographically
      represent important turning points, which concerned people have to cope and deal
      with. While biographical research, which is established in the human and social
      sciences, has been dealing for a long time with typical features, such as on the
      type of a disease-dependent burden and coping processes, biographical oriented
      research approaches in nursing science are in their early stages. The article at
      hand has its goal in discussing the connectivity, particularly the social
      interpretative biographical research in nursing science and their relevance for
      the development of supporting concepts regarding nursing; with the intention to
      rehabilitate the sufferer as the author of his own life story.

PMID- 16794884
TI  - [Managing chronic illness implications for the health care system].
AB  - Although chronic diseases build the main focus of health problems, the German
      health care system is not sufficiently prepared to deal with the new challenges.
      The reasons are diverse, but one of the most decisive is that the various
      consequences in dealing with chronic disease are scarcely noticed by the health
      service. These consequences are brought out by the following article by referring
      to the available literature and our own studies and are discussed in its
      implications for a needs-driven design of care. Special attention is paid to
      care, because it increasingly assumes a key role in the treatment of chronically
      ill, which still faces barriers in this country. These discussed are also.

PMID- 16794885
TI  - [Investment of time in long-term care].
AB  - In a survey involving 230 persons in need of long-term care, the time required to
      perform support and nursing care measures was recorded and the time slices of the
      different contributors to the nursing care tasks were assessed. The results gave
      clear evidence that the amount of working time is not only depending on the
      severity of the case, but likewise influenced by determining factors linked to
      the social background. In equally less severe cases, the time spent on nursing
      care varied from 20 to 100 hours. In particular those with a main carer assigned
      to liberal civic culture, a weak informal support network and residence in an
      urban environment will face disadvantages regarding the time spent on their
      support.

PMID- 16794886
TI  - [The German nursing expert standards: powerful instruments to improve nursing
      practice or of doubtful benefit?].
AB  - The German Network for the Development of Quality in Nursing has published so
      called "National Expert Standards" on selected nursing issues. These are
      implemented into nursing practice, used by health authorities to evaluate the
      quality of nursing care and also for legal judgement. Evidence-based quality
      criteria for practice guidelines are currently not met. The expert standards lack
      rigorous methods for development, transparent reporting and clarity.
      Implementation tools to allow structured implementation are not provided. Vague
      recommendations offer various possibilities of interpretation. Effectiveness of
      the expert standards has not yet been proven. Future nursing guidelines should
      take into account international quality criteria.

PMID- 16794887
TI  - [The use of volunteers to support family carers of dementia patients: results of
      a prospective longitudinal study investigating expectations towards and
      experience with training and professional support].
AB  - Caring for a dementia patient in the family often turns out to be a full-time job
      for family carers. So home visitors-for example volunteers spending time with the
      patient and thus offering some respite to the family-may be a very important
      aspect of stabilizing home care. This study investigates the expectations of
      volunteers concerning their training and their future voluntary work, as well as
      their visiting experiences, and their reasons for stopping the voluntary work. A
      total of 40 volunteers were interviewed three times over a 18 month period. The
      interviews were based on interview guidelines and were problem-centered. The
      interviewees' replies were subject to a summarizing qualitative content analysis.
      Of the study participants 85% were women, 48% had previously been family carers
      themselves, and 50% had previous experience of other voluntary work. Their wish
      "to do something useful" and "to learn more about dementia" were the main reasons
      for participation in voluntary work. The interviewed persons tend to learn most
      about communicating with dementia patients through case studies and practical
      exercises. Work pressures or restarting employment were the most common reasons
      to stop the voluntary work. Only if the volunteers are supported by professionals
      -particularly in the form of a contact person who is always available when
      problems occur--can this type of respite for family carers be maintained.

PMID- 16794888
TI  - [Predictors of personal growth among caregivers of dementia patients].
AB  - Much of the research on caregiving has focussed on burden, stress, and coping,
      but there may also be positive outcomes associated with the process of care.
      Relatives caring for dementia patients report that they have grown more mature
      personally and gain a better idea of what is important in life. The purpose of
      this study is to look at predictors of personal growth. A total of 888 relatives
      of patients with dementia were examined. We found, using ordinary least squares
      regression, that personal growth was correlated with stressors and context
      variables like duration of caregiving, lack of social recognition, and the need
      for help with Activities of Daily Living (ADL) in the person with dementia.
      Personal growth through caregiving was predicted by duration of caregiving during
      the first years of caregiving. These findings underscore the importance of the
      negative aspects (stress, burden, long duration) that contribute to the
      development of personal growth through care.

PMID- 16794889
TI  - [Attitudes towards predictive genetic testing for Alzheimer's disease].
AB  - Most neuropsychiatric disorders have a complex aetiology. Discovery of the
      underlying genetics will provide insights into the disorders and allow the
      subsequent development of therapeutic interventions based upon an understanding
      of causality. The first vulnerability genes in Alzheimer's disease (AD) have been
      identified. The contribution of each vulnerability gene to the disorder is
      limited and does not enable prediction of course and onset in individual cases,
      only modification of the a priori risk. However, people may wish to be informed
      about this modification. Professionals have not favoured this form of predictive
      testing due to an awareness of its limitations and its potential for harm.
      However, little is known about public attitudes and understanding of such genetic
      testing in neuropsychiatric disorders. The aim of our study was to assess the
      attitudes of the general population and to explore the influence on these
      attitudes of knowledge about the illness and the understanding of risk
      information. In our study, a representative sample of the German general
      population (n=2001), relatives of patients with Alzheimer's disease (n=101) and
      physicians (n=43) were interviewed about their attitudes towards genetic tests
      for Alzheimer's disease and their perception and interpretation of risk
      information. To assess the influence of genetic counselling on these factors, 234
      people were questioned before, and four weeks after, they were provided with
      detailed relevant information. Our results indicate that a substantial proportion
      of the German population (57%) is in favour of psychiatric genetic testing for AD
      in general. Even when the explanatory power of a genetic test is limited, a
      substantial proportion of the population (47%) expressed an interest in genetic
      testing. Counselling slightly decreased the interest in having a genetic test for
      oneself (from 47% to 38%). Physicians were more hesitant than both relatives and
      the general population concerning predictive genetic testing. Only a minority
      (11%) favoured prenatal genetic testing. Our results also show that both
      knowledge about AD and the capacity to interpret risk estimates are limited.
      While physicians' estimation of their personal risk for developing AD
      approximated to the actual average risk for the population, people in the general
      population and the relatives of AD patients tended to overestimate their personal
      risk. However, most of the general population still perceived this risk as
      average or low. While most physicians could correctly interpret information
      regarding the probability of risk, only one third of AD patients' relatives or
      members of the general population could. As the decision of an individual to
      undergo predictive testing relies mainly on his understanding of risk, the
      ability to correctly interpret risk information will be of crucial importance in
      the future. From a medical perspective, the prevailing approach of professional
      associations to genetic testing appears reasonable and therefore should not be
      changed at present.

PMID- 16794892
TI  - The effect of addition of nitrous oxide to a sevoflurane anesthetic on BIS, PSI,
      and entropy.
AB  - OBJECTIVE: N(2)O is a commonly used anesthetic that has amnestic and analgesic
      properties. Recently, devices that estimate depth of consciousness have been
      introduced in an attempt to better titrate anesthesia, however the effect of
      N(2)O on these monitors is unclear. METHODS: General anesthesia was induced and
      titrated to maintain normal blood pressure and pulse in healthy adults. Data were
      collected in three 10 minute intervals (Sevo, Sevo + N(2)O, Sevo). In Phase A,
      sevoflurane concentration was held constant during the N(2)O trial in 60 subjects
      monitored with either BIS, PSI, or Entropy. In Phase B, sevoflurane concentration
      was reduced as N(2)O was added, maintaining a constant overall "MAC" in 20
      subjects monitored concurrently with BIS and Entropy. Sample size for both phases
      was designed to detect a 10 unit change in measure of processed EEG with alpha =
      .05 and statistical power = .80. RESULTS: In Phase A, supplementing sevoflurane
      with > 65% N(2)O increased MAC from 1.3 +/- 0.05 to 2.2 +/- 0.10, but did not
      significantly alter BIS nor PSI (p-value for differential MAC is < 0.05).
      Entropy, however, dropped significantly, with a change in state entropy (SE) from
      31.1 +/- 7.3 to 18.9 +/- 3.7 and a corresponding rise when N(2)O was
      discontinued. In Phase B, supplementing sevoflurane with > 65% N(2)O with a
      concomitant reduction in sevoflurane resulted in an increase in both BIS (from 34
      +/- 5 to 53.9 +/- 11.5) and SE (from 32 +/- 8.2 to 55.4 +/- 21.3). CONCLUSION:
      Supplementing sevoflurane with > 65% N(2)O did not result in a significant change
      in either BIS or PSI when sevoflurane concentration was kept constant. Entropy,
      however, significantly decreased as anesthetic depth increased. When sevoflurane
      concentration was reduced during N(2)O administration, both BIS and Entropy rose
      despite maintenance of anesthetic depth, indicating a variable concentration
      effect between volatiles and N(2)O.

PMID- 16794893
TI  - Complications of transfemoral removal of percutaneous transfemorally implanted
      port-catheter systems.
AB  - Our purpose is to evaluate the feasibility and safety of the withdrawal procedure
      of percutaneous transfemorally implanted port-catheter systems. Thirty-seven
      patients (17.7%) underwent the withdrawal procedure of this port-catheter system
      among 209 patients. The reasons for withdrawal were as follows: termination of
      intra-arterial chemotherapy (n = 7), obstruction of hepatic artery (n = 5), port
      infection (n = 4), catheter infection (n = 4), catheter obstruction (n = 4),
      lower-limb palsy and pain (n = 2), exposure of the port due to skin defect (n =
      2), patient's desire (n = 2), side effect of chemotherapy (n = 1), no
      effectiveness of chemotherapy (n = 1), hematoma at the puncture site (n = 1),
      duodenum perforation by the catheter (n = 1), intermittent claudication due to
      severe stenosis of right common iliac artery (n = 1), dissection of common
      hepatic artery (n = 1), and broken catheter (n = 1). In thirty-four of the 37
      cases, the port-catheter system was successfully withdrawn without any
      complications. Clinical success rate was 91.9%. Complications occurred in three
      cases (8.1%), which were a pseudoaneurysm, thromboembolism of the right common
      iliac artery, and continuous bleeding from the subcutaneous pocket where the port
      system was placed for 1 month. In 15 cases, correction of the catheter tip or
      exchange for dislocation of the tip had to be done without withdrawal. It is not
      rare to withdraw port-catheter systems in cases of infection or hematoma around
      the system. Although withdrawal of a percutaneous transfemorally implanted port
      catheter system is a relatively safe procedure, the port-catheter system should
      not be removed unless absolutely indicated.

PMID- 16794894
TI  - Selective embolization of large symptomatic iatrogenic renal transplant
      arteriovenous fistula.
AB  - We report on the successful treatment of hypertension by occlusion of a large
      iatrogenic renal transplant arteriovenous fistula using detachable embolization
      coils with concomitant flow reduction by occlusion balloon in two patients.

PMID- 16794895
TI  - Evaluation of polyurethane nasolacrimal duct stents: in vivo studies in New
      Zealand rabbits.
AB  - The purpose of this study was to evaluate the radiographic and biological effects
      of different polyurethane nasolacrimal duct stents in an animal model. Fifteen
      polyurethane nasolacrimal duct stents (n = 5 mushroom-type stents, n = 5 newly
      designed S-shaped TearLeader stents without hydrophilic coating, and n = 5 S
      shaped TearLeader stents with hydrophilic coating) were implanted in the
      nasolacrimal ducts of eight unaffected New Zealand rabbits. One nasolacrimal
      system served as control. Clinical and radiographic follow-up was performed at 1
      , 2-, and 4-week intervals, then after a 3-month interval, after which the
      animals were euthanized. All stents were implanted without major periprocedural
      complications. The stents proved to be patent by the end of the procedure. During
      follow-up, all mushroom-type stents were occluded at 4 weeks. None of these
      stents opened to forced irrigation. Clinically, all rabbits demonstrated severe
      dacryocystitis. Three out of five TearLeader stents without hydrophilic coating
      were blocked at 4 weeks; one out of five was open to irrigation. Best results
      were observed in the stent group with hydrophilic coating. Follow-up
      dacryocystography demonstrated patent stents in nasolacrimal ducts of all animals
      after 4 weeks. In only one of five cases, the coated stent became partially
      occluded after 2 months. These animals were free of clinical symptoms. After 3
      months, at least three out of five stents still opened to forced irrigation and
      only one stent was completely blocked. Dislocation of the stents was not
      observed. Refinement of the stent surface and stent design improves the results
      of nasolacrimal duct stenting in this animal model. Implantation of hydrophilic
      coated S-shaped stents is highly superior to conventional mushroom-type stents
      and noncoated stent types. Hydrophilic coating seems to prevent foreign-body
      reactions, resulting in maximized stent patency.

PMID- 16794896
TI  - Comparison of two foreign body retrieval devices with adjustable loops in a swine
      model.
AB  - The purpose of the study was to compare two similar foreign body retrieval
      devices, the Texan (TX) and the Texan LONGhorn (TX-LG), in a swine model. Both
      devices feature a < or = 30-mm adjustable loop. Capture times and total procedure
      times for retrieving foreign bodies from the infrarenal aorta, inferior vena
      cava, and stomach were compared. All attempts with both devices (TX, n = 15; TX
      LG, n = 14) were successful. Foreign bodies in the vasculature were captured
      quickly using both devices (mean +/- SD, 88 +/- 106 sec for TX vs 67 +/- 42 sec
      for TX-LG) with no significant difference between them. The TX-LG, however,
      allowed significantly better capture times than the TX in the stomach (p =
      0.022), Overall, capture times for the TX-LG were significantly better than for
      the TX (p = 0.029). There was no significant difference between the total
      procedure times in any anatomic region. TX-LG performed significantly better than
      the TX in the stomach and therefore overall. The better torque control and
      maneuverability of TX-LG resulted in better performance in large anatomic spaces.

PMID- 16794897
TI  - Percutaneous vertebroplasty: preliminary experiences with rotational acquisitions
      and 3D reconstructions for therapy control.
AB  - Percutaneous vertebroplasty (PVP) is carried out under fluoroscopic control in
      most centers. The exclusion of implant leakage and the assessment of implant
      distribution might be difficult to assess based on two-dimensional radiographic
      projection images only. We evaluated the feasibility of performing a follow-up
      examination after PVP with rotational acquisitions and volumetric reconstructions
      in the angio suite. Twenty consecutive patients underwent standard PVP procedures
      under fluoroscopic control. Immediate postprocedure evaluation of the implant
      distribution in the angio suite (BV 3000; Philips, The Netherlands) was performed
      using rotational acquisitions (typical parameters for the image acquisition
      included a 17-cm field-of-view, 200 acquired images for a total angular range of
      180 degrees ). Postprocessing of acquired volumetric datasets included
      multiplanar reconstruction (MPR), maximum intensity projection (MIP), and volume
      rendering technique (VRT) images that were displayed as two-dimensional slabs or
      as entire three-dimensional volumes. Image evaluation included lesion and implant
      assessment with special attention given to implant leakage. Findings from
      rotational acquisitions were compared to findings from postinterventional CT. The
      time to perform and to postprocess the rotational acquisitions was in all cases
      less then 10 min. Assessment of implant distribution after PVP using rotational
      image acquisition methods and volumetric reconstructions was possible in all
      patients. Cement distribution and potential leakage sites were visualized best on
      MIP images presented as slabs. From a total of 33 detected leakages with CT, 30
      could be correctly detected by rotational image acquisition. Rotational image
      acquisitions and volumetric reconstruction methods provided a fast method to
      control radiographically the result of PVP in our cases.

PMID- 16794898
TI  - Meta-analyses in cancer clinical trials: principles and pitfalls.

PMID- 16794899
TI  - Developing countries: an evolving opportunity for oncologic research.

PMID- 16794900
TI  - Clinical trials in surgery: the role of the American College of Surgeons Oncology
      Group.

PMID- 16794901
TI  - Quality of life assessment in surgical oncology trials.
AB  - Integrating health-related quality of life (HRQOL) as an endpoint for randomized
      surgical trials provides valuable insight into the patients' perspective on
      treatment outcome. Health related quality of life data also play a role in
      ensuring fully informed consent, determining treatment options and informing
      treatment decision making. However, few randomized surgical trials have been
      conducted that meet the minimum requirements for rigorous HRQL assessment and,
      despite increasing efforts to improve the reporting of randomized trials, many
      are still not adequately performed. Such methodologic limitations may influence
      trial findings for HRQL outcomes and undermine the ability of the data collected
      to inform clinical practice. This review describes key methodological aspects of
      HRQL assessment that are required in randomized trials to ensure that data are
      robust. This includes choice of HRQL instrument, the method and timing of
      assessments and data analysis and presentation. The review also makes
      recommendations for future research in this area.

PMID- 16794902
TI  - Design of cancer screening trials/randomized trials for evaluation of cancer
      screening.

PMID- 16794903
TI  - Clinical trial results applied to management of the individual cancer patient.
AB  - The application of clinical trial results to the management of the individual
      cancer patient is not always straightforward. The results of a clinical trial
      indicate the "average" effect of an intervention, often expressed in terms of an
      absolute risk reduction, which is an estimate of the likelihood of benefit for a
      particular patient. However, within any clinical trial, there might be
      differences between groups of patients in underlying pathology, genetics, or
      biology, and some patients might benefit more from a new treatment than others.
      Thus, within a clinical trial, it might also be useful to group together patients
      with similar characteristics, and test for subgroup interaction. The test for
      interaction will indicate whether the magnitude of benefit differs from one
      prognostic subgroup to the next (a quantitative interaction). Much less common
      are qualitative interactions, in which a new treatment is beneficial in one
      subgroup but harmful in another. If the test for subgroup interaction is
      significant, then the effects of treatment may indeed differ between subgroups of
      patients, but this should be confirmed in other trials before a treatment is
      implemented in clinical practice.

PMID- 16794905
TI  - Assessment of the preserved function of the remnant stomach in pylorus-preserving
      gastrectomy by gastric emptying scintigraphy.
AB  - BACKGROUND: This study evaluated the preserved function of the remnant stomach by
      gastric emptying scintigraphy in patients who underwent pylorus-preserving
      gastrectomy (PPG), and it investigated whether this examination method is a
      useful tool for evaluation. MATERIALS AND METHODS: The residual stomach function
      was evaluated by gastric emptying scintigraphy in 45 patients with early gastric
      cancer who had undergone PPG. 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.
      RESULTS: Seventy-three percent of the PPG patients were classified as belonging
      to the intermediate emptying type, and the remainder to the delayed emptying
      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. It was difficult to estimate gastric
      emptying function from endoscopic findings. CONCLUSIONS: 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.

PMID- 16794906
TI  - Reoperative surgery for chronic pancreatitis: is it safe?
AB  - INTRODUCTION: Eleven percent to fifty-six percent of patients do not achieve
      adequate pain relief with initial operative treatment for chronic pancreatitis,
      and reoperations for recurrent or persistent pain are common. This study
      evaluates the influence of prior pancreatic procedures on operative morbidity for
      chronic pancreatitis. METHODS: The records of 336 consecutive patients who
      underwent pancreaticoduodenectomy (PD, n=78), lateral pancreaticojejunostomy
      (LPJ, n=152), distal pancreatectomy (DP, n=83), transduodenal sphincteroplasty
      (SP, n=20), and total pancreatectomy (TP, n=3) for chronic pancreatitis were
      retrospectively reviewed and analyzed. RESULTS: Seventy-four patients underwent
      reoperation after failed prior pancreatic surgery. Patients with de novo
      pancreatic operations had a similar complication rate as those with reoperation
      (PD: 48% versus 65%, P>0.05; LPJ: 23% versus 23%, P>0.05; DP: 26% versus 28%,
      P>0.05; SP: 21% versus 100%, P>0.05). Major complications such as pancreatic leak
      or abdominal abscess were similar in the two groups. Minor complications such as
      delayed gastric emptying or wound infections were more common in the reoperation
      group. There was no difference in postoperative hospital length of stay.
      CONCLUSIONS: Patients who undergo reoperative surgery for chronic pancreatitis
      have an increased risk for minor perioperative complications. The overall
      complication rate and the incidence of major complications are similar compared
      to de novo procedure. Reoperative surgery therefore appears feasible and safe in
      experienced hands.

PMID- 16794907
TI  - Partial median sternotomy: an attractive approach to mediastinal parathyroid
      disease.
AB  - BACKGROUND: Parathyroid exploration through a standard cervical approach is
      adequate for the resection of most mediastinal parathyroid glands. A subset of
      mediastinal parathyroid glands causing hyperparathyroidism, however, cannot be
      removed in this manner. STUDY DESIGN: We reviewed our experience with the use of
      partial median sternotomy in the treatment of these patients. RESULTS: Over a 14
      year period, all but 10 of 937 (1.1%) consecutive patients explored for
      hyperparathyroidism by a single endocrine surgeon were treated by a cervical
      approach. Partial median sternotomy was performed in 10 cases and was successful
      in seven cases (70%), with conversion to a complete sternotomy being required in
      three cases. Six of these seven patients had failed a previous parathyroid
      exploration (86%), including one patient who had a previous complete sternotomy.
      Cure of hyperparathyroidism was achieved in all seven patients undergoing partial
      median sternotomy. In five patients a mediastinal parathyroid gland was removed
      (71%), and in one patient a parathyroid adenoma in the carotid sheath was
      eventually found, and the location of the hyperfunctioning parathyroid gland in
      one patient was never determined although the patient was cured. The mean length
      of hospital stay after a partial median sternotomy was 2.6 days. One patient
      sustained a recurrent laryngeal nerve injury at the time of a repeat cervical
      exploration and partial median sternotomy. CONCLUSIONS: Rarely, mediastinal
      parathyroid glands cannot be resected through a cervical approach. In these cases
      the use of partial median sternotomy is an attractive technique in achieving cure
      of hyperparathyroidism and is associated with minimal morbidity and a short
      length of hospital stay.

PMID- 16794908
TI  - Postsurgical infections are reduced with specialized nutrition support.
AB  - OBJECTIVE: The objective was to examine the relationship between pre-, peri-, and
      postoperative specialized nutritional support with immune-modulating nutrients
      and postoperative morbidity in patients undergoing elective surgery. METHODS:
      Studies were identified by searching MEDLINE, review article bibliographies, and
      abstracts and proceedings of scientific meetings. All randomized clinical trials
      in which patients were supplemented by the IMPACT formula before and/or after
      elective surgery and the clinical outcomes reported were included in the meta
      analysis. Seventeen studies (n=2,305), 14 published (n=2,102), and 3 unpublished
      (n=203), fulfilled the inclusion criteria. Ten studies (n=1,392) examined the
      efficacy of pre- or perioperative IMPACT supplementation in patients undergoing
      elective surgery, whereas 7 (n=913) assessed postoperative efficacy. Fourteen of
      the studies (n=2,083) involved gastrointestinal (GI) surgical patients.
      Postoperative complications, mortality, and length of stay in hospital (LOS) were
      major outcomes of interest. RESULTS: IMPACT supplementation, in general, was
      associated with significant (39%-61%) reductions in postoperative infectious
      complications and a significant decrease in LOS in hospital by an average of 2
      days. The greatest improvement in postoperative outcomes was observed in patients
      receiving specialized nutrition support as part of their preoperative treatment.
      In GI surgical patients, anastomotic leaks were 46% less prevalent when IMPACT
      supplementation was part of the preoperative treatment. CONCLUSION: This study
      identifies a dosage (0.5-1 l/day) and duration (supplementation for 5-7 days
      before surgery) of IMPACT that contributes to improved outcomes of morbidity in
      elective surgery patients, particularly those undergoing GI surgical procedures.
      The cost effectiveness of such practice is supported by recent health economic
      analysis. Findings suggest preoperative IMPACT use for the prophylaxis of
      postoperative complications in elective surgical patients.

PMID- 16794909
TI  - The landmark surgical trials of the National Surgical Adjuvant Breast and Bowel
      Project.
AB  - In this paper we provide a summary of several of the completed and ongoing
      surgical trials of the National Surgical Adjuvant Breast and Bowel Project, one
      of the cancer cooperative trials groups supported by the US National Cancer
      Institute.

PMID- 16794910
TI  - Establishment of a varicose vein center in a tertiary vascular surgery practice:
      urban versus rural differences.
AB  - We examined changes in practice patterns after the establishment of a varicose
      vein center (VVC) within two tertiary university vascular surgery practices and
      compared differences between urban (U) and rural (R) sites. Practice patterns for
      the treatment of VVs were compared 3 years before (period 1) and 3 years after
      (period 2) the formation of a U-VVC and an R-VVC in 2001. Both VVCs were part of
      similar-sized tertiary vascular surgery practices. Evaluation was specific to
      VVs, reticular veins, and telangiectasias. Prior to U-VVC, there were 338 office
      visits, six office procedures, and 114 hospital procedures. After U-VVC, there
      were 624, 120, and 312, respectively. Prior to R-VVC, there were 85 office
      visits, five office procedures, and 69 hospital procedures. After R-VVC, there
      were 528, 163, and 303, respectively. In period 1 for U-VVC and R-VVC, VVC
      relative value unit (RVU) generation as a percent of total practice RVUs was 1.0%
      and 0.7%, respectively. In period 2 for U-VVC and R-VVC, VVC RVU generation as a
      percent of total practice RVUs was 2.6% and 2.5%, respectively. In an effort to
      provide more coordinated treatment for patients with VVs, establishing a VVC
      within a tertiary academic vascular surgery practice can lead to rapid expansion
      of clinical volume by increased office visits, office procedures, and hospital
      procedures. Clinical demand for evaluation and treatment of VVs showed little
      variation between R-VVC and U-VVC.

PMID- 16794911
TI  - Cardiac medical therapy among patients undergoing abdominal aortic aneurysm
      repair.
AB  - Open abdominal aortic aneurysm (AAA) repair is a common surgical procedure
      associated with high mortality rates. Our objective was to describe the use of in
      hospital cardiac medical therapy among patients undergoing open AAA repair and to
      examine the effect of perioperative cardiac medical therapy on in-hospital
      mortality. We examined clinical data and in-hospital medication use among 223
      patients who underwent open AAA repair at three North American hospitals, all of
      which used the Transition resource and cost accounting system. Medication use was
      described [angiotensin converting enzyme (ACE) inhibitors, aspirin, ss-blockers,
      and statins] within the cohort at five specific periods of time: presurgery, day
      of surgery, 1 day after surgery, postsurgery, and discharge. We then performed a
      matched case-control study where cases were defined as patients who died in
      hospital. We compared medication use between cases and controls to assess its
      impact on in-hospital mortality. Most patients were elderly (mean age 72.5 +/-
      9.8 years), 70.4% were male, and in-hospital mortality within the cohort was
      10.8%. Medication use in all periods of administration was low. ss-Blocker use
      was highest among all classes on the day of surgery, with 20.6% of patients
      undergoing AAA repair receiving the medication. Less than 50% of patients
      received any of the medications at discharge. After adjusting for baseline
      differences, perioperative ACE inhibitor use showed a trend toward a protective
      effect [odds ratio (OR) = 0.09, 95% confidence interval (CI) 0.01-1.31, p =
      0.08], and perioperative ss-blocker use was significantly associated with a
      decrease in mortality (OR = 0.07, 95% CI 0.01-0.87, p = 0.04). Cardiac medical
      therapy among patients undergoing AAA repair is low throughout all periods of
      hospitalization. ACE inhibitor and ss-blocker use may be associated with
      decreased in-hospital mortality.

PMID- 16794913
TI  - Current-level discrimination in the context of interleaved, multichannel
      stimulation in cochlear implants: effects of number of stimulated electrodes,
      pulse rate, and electrode separation.
AB  - The ability of cochlear implantees to detect an increment in current level at one
      of many stimulated electrodes was investigated. Such changes in the electric
      profile provide information for cochlear implantees to discriminate numerous
      sounds, especially vowels. In Experiment 1, sensitivity to increases in current
      level at one stimulation site in the electric profile decreased as the number of
      stimulated electrodes increased. This outcome was most likely a result of
      decreased stimulus levels at individual electrodes that were required to retain a
      comfortable loudness when the number of active electrodes was increased.
      Experiment 2 investigated the effects of pulse rate and separation between
      stimulation sites when the levels in percent of dynamic range and number of
      stimulated electrodes were held constant. The effect of pulse rate and electrode
      separation varied among listeners. The sensitivity of 6 of 9 listeners was best
      at the pulse rate that they used clinically. This might have been the result of
      adaptation to the clinical pulse rate, or listeners might have chosen their
      inherently best pulse rate during the clinical fitting.

PMID- 16794912
TI  - Age-related changes in cochlear gene expression in normal and shaker 2 mice.
AB  - The vertebrate cochlea is a complex organ optimized for sound transduction.
      Auditory hair cells, with their precisely arranged stereocilia bundles, transduce
      sound waves to electrical signals that are transmitted to the brain. Mutations in
      the unconventional myosin XV cause deafness in both human DFNB3 families and in
      shaker 2 (sh2) mice as a result of defects in stereocilia. In these mutant mice,
      hair cells have relatively normal spatial organization of stereocilia bundles but
      lack the graded, stair-step organization. We used sh2 mice as an experimental
      model to investigate the molecular consequences of the sh2 mutation in the Myo15
      gene. Gene expression profiling with Affymetrix GeneChips in deaf homozygous
      (sh2/sh2) mice at 3 weeks and 3 months of age, and in age-matched, normal-hearing
      heterozygotes (+/sh2) identified only a few genes whose expression was affected
      by genotype, but a large number with age-associated changes in expression in both
      normal mice and sh2/sh2 homozygotes. Microarray data analyzed using Robust
      Multiarray Average identified Aim1, Dbi, and Tm4sf3 as genes with increased
      expression in sh2/sh2 homozygotes. These increases were confirmed by quantitative
      reverse transcription-polymerase chain reaction. Genes exhibiting altered
      expression with age encoded collagens and proteins involved in collagen
      maturation, extracellular matrix, and bone mineralization. These results
      identified potential cellular pathways associated with myosin XV defects, and age
      associated molecular events that are likely to be involved in maturation of the
      cochlea and auditory function.

PMID- 16794914
TI  - Heat shock inhibits both aminoglycoside- and cisplatin-induced sensory hair cell
      death.
AB  - Human hearing and balance impairments are often attributable to the death of
      sensory hair cells in the inner ear. These cells are hypersensitive to death
      induced by noise exposure, aging, and some therapeutic drugs. Two major classes
      of ototoxic drugs are the aminoglycoside antibiotics and the antineoplastic agent
      cisplatin. Exposure to these drugs leads to hair cell death that is mediated by
      the activation of specific apoptotic proteins, including caspases. The induction
      of heat shock proteins (HSPs) in response to cellular stress is a ubiquitous and
      highly conserved response that can significantly inhibit apoptosis in some
      systems by inhibiting apoptotic proteins. Induction of HSPs occurs in hair cells
      in response to a variety of stimuli. Given that HSPs can directly inhibit
      apoptosis, we hypothesized that heat shock may inhibit apoptosis in hair cells
      exposed to ototoxic drugs. To test this hypothesis, we developed a method for
      inducing HSP expression in the adult mouse utricle in vitro. In vitro heat shock
      reliably produces a robust up-regulation of HSP-70 mRNA and protein, as well as
      more modest up-regulation of HSP-90 and HSP-27. The heat shock does not result in
      death of hair cells. Heat shock has a significant protective effect against both
      aminoglycoside- and cisplatin-induced hair cell death in the utricle preparation
      in vitro. These data indicate that heat shock can inhibit ototoxic drug-induced
      hair cell death, and that the utricle preparation can be used to examine the
      molecular mechanism(s) underlying this protective effect.

PMID- 16794916
TI  - Feedback loops, reversals and nonlinearities in lymphocyte development.
AB  - Systems of differentiating cells are often regarded by experimental biologists as
      unidirectional processes, in which cells spend a fixed time at each successive
      developmental stage. However, mathematical modeling has in several cases revealed
      that differentiating cell systems are more complex than previously believed. For
      example, non-linear transitions, feedback effects, and even apparent reversals
      have been suggested by our studies on models for the development of lymphocytes
      and their receptor repertoires, and are reviewed in this paper. These studies
      have shown that cell population growth in developing lymphocyte subsets is
      usually nonlinear, as it depends on the density of cells in each compartment.
      Additionally, T cell development has been shown to be subject to feedback
      regulation by mature T cell subsets, and B cell development has been shown to
      include a phenotypic reflux from an advanced to an earlier developmental stage.
      The challenges we face in our efforts to understand how the repertoires of these
      cells are generated and regulated are also discussed here.

PMID- 16794915
TI  - Polarization and movement of keratocytes: a multiscale modelling approach.
AB  - Eukariotic cell motility is a complex phenomenon, in which the cytoskeleton and
      its major constituent, actin, play an essential role. Actin forms polymers of
      long, stiff filaments that are cross-linked into an anisotropic network inside a
      thin sheet-like cellular protrusion, the lamellipod. At the leading edge of this
      structure, polymerization of actin filaments creates the force that pushes out
      the membrane and leads to translocation of a motile cell. Dynamics of the actin
      network account for changes in cell shape, crawling motion and turning of the
      cell in response to external cues. Regulating the dynamics of the cytoskeleton,
      and playing a central role in signal transduction in the cell, are Cdc42, Rac and
      Rho (GTPases of the rho family, collectively known as the small G-proteins) and
      the actin nucleating complex, Arp2/3. In this paper, we use a multiscale
      modelling approach in a 2D model of a motile cell. We describe the mutual
      interactions of the small G-proteins, and their effects on capping and side
      branching of actin filaments. We incorporate the pushing exerted by oriented
      actin filament ends on the cell edge, and a Rho-dependent contraction force.
      Combining these biochemical and mechanical aspects, we investigate the dynamics
      of a model epidermal fish keratocyte through in silico experiments. Our model
      gives insight into how, in response to some cue, a cell can polarize, form a
      leading edge, and move; concomitantly it explains how a keratocyte cell can
      maintain its shape and polarity, even after removal of the initial stimulus, and
      how it can change direction quickly in response to changes in its environment. We
      show that establishment of polarity stems from interactions of Cdc42, Rac and
      Rho, while maintenance and robustness of polarity is due to the rapid cytosolic
      diffusion of the inactive (GDI-bound) forms of the small G-proteins. Our model
      produces a cell shape that closely resembles the keratocytes and correct speeds
      for biologically reasonable parameter values. Movies of the simulations can be
      obtained from http://theory.bio.uu.nl/stan/keratocyte.

PMID- 16794917
TI  - Science as a medium for friendship: how the Keller-Segel models came about.

PMID- 16794919
TI  - Traveling waves and spread rates for a West Nile virus model.
AB  - A reaction-diffusion model for the spatial spread of West Nile virus is developed
      and analysed. Infection dynamics are based on a modified version of a model for
      cross infection between birds and mosquitoes (Wonham et al., 2004, An
      epidemiological model for West-Nile virus: Invasion analysis and control
      application. Proc. R. Soc. Lond. B 271), and diffusion terms describe movement of
      birds and mosquitoes. Working with a simplified version of the model, the
      cooperative nature of cross-infection dynamics is utilized to prove the existence
      of traveling waves and to calculate the spatial spread rate of infection.
      Comparison theorem results are used to show that the spread rate of the
      simplified model may provide an upper bound for the spread rate of a more
      realistic and complex version of the model.

PMID- 16794920
TI  - Modelling directional guidance and motility regulation in cell migration.
AB  - Although cell migration is an essential process in development, how cells reach
      their final destination is not well understood. Secreted molecules are known to
      have a migratory effect, but it remains unclear whether such molecules act as
      directional guidance cues or as motility regulators. There is potential to use
      signalling molecules in new medical therapies, so it is important to identify the
      exact role these molecules play. This paper focuses on distinguishing between
      inhibitory and repulsive effects produced by signalling molecules, based on
      recent experiments examining the effect of Slit, a secreted protein, on the
      migration of neurons from the brain. The primary role of Slit, whether it is an
      inhibitor or repellent of neurons, is in dispute. We present population-level
      continuum models and recast these in terms of transition probabilities governing
      individual cells. Various cell-sensing strategies are considered within this
      framework. The models are applied to the neuronal migration experiments. To
      resolve the particular role of Slit, simulations of the models characterising
      different cell-sensing strategies are compared at the population and individual
      cell level, providing two complementary perspectives on the system. Difficulties
      and limitations in deducing cell migration rules from time-lapse imaging are
      discussed.

PMID- 16794921
TI  - Fluid mechanics of the human eye: aqueous humour flow in the anterior chamber.
AB  - We consider and compare the various different kinds of flow that may take place
      in the anterior chamber of a human eye. The physical mechanisms responsible for
      causing such flows may be classified as follows: (i) buoyancy-driven flow arising
      from the temperature difference between the anterior surface of the cornea and
      the iris, (ii) flow generated by the aqueous production of the ciliary body,
      (iii) flow generated by the interaction between buoyancy and gravity while
      sleeping while sleeping in a face-up position, (iv) flow generated by
      phakodenesis (lens tremor), (v) flow generated by Rapid Eye Movement (REM) during
      sleep. Each flow is studied using a traditional fluid mechanics/asymptotic
      analysis approach. We also assess the veracity of a hypothesis that was recently
      advanced [see Maurice, D.M., 1998. The Von Sallman Lecture 1996: An
      ophthalmological explanation of REM sleep. Exp. Eye. Res. 66, 139-145, for
      details] to suggest that, contrary to previous opinion, the purpose of REM during
      sleep is to ensure corneal respiration in the absence of the buoyant mixing that
      routinely takes place due to (i) above during waking conditions.

PMID- 16794922
TI  - A developmental model of ocular dominance column formation on a growing cortex.
AB  - We derive an activity-based developmental model of ocular dominance column
      formation in primary visual cortex that takes into account cortical growth. The
      resulting evolution equation for the densities of feedforward afferents from the
      two eyes exhibits a sequence of pattern forming instabilities as the size of the
      cortex increases. We use linear stability analysis to investigate the nature of
      the transitions between successive patterns in the sequence. We show that these
      transitions involve the splitting of existing ocular dominance (OD) columns, such
      that the mean width of an OD column is approximately preserved during the course
      of development. This is consistent with recent experimental observations of
      postnatal growth in cat.

PMID- 16794923
TI  - Gene expression time delays and Turing pattern formation systems.
AB  - The incorporation of time delays can greatly affect the behaviour of partial
      differential equations and dynamical systems. In addition, there is evidence that
      time delays in gene expression due to transcription and translation play an
      important role in the dynamics of cellular systems. In this paper, we investigate
      the effects of incorporating gene expression time delays into a one-dimensional
      putative reaction diffusion pattern formation mechanism on both stationary
      domains and domains with spatially uniform exponential growth. While oscillatory
      behaviour is rare, we find that the time taken to initiate and stabilise patterns
      increases dramatically as the time delay is increased. In addition, we observe
      that on rapidly growing domains the time delay can induce a failure of the Turing
      instability which cannot be predicted by a naive linear analysis of the
      underlying equations about the homogeneous steady state. The dramatic lag in the
      induction of patterning, or even its complete absence on occasions, highlights
      the importance of considering explicit gene expression time delays in models for
      cellular reaction diffusion patterning.

PMID- 16794924
TI  - A Brownian Dynamics model of kinesin in three dimensions incorporating the force
      extension profile of the coiled-coil cargo tether.
AB  - The kinesin family of motor proteins are involved in a variety of cellular
      processes that transport materials and generate force. With recent advances in
      experimental techniques, such as optical tweezers can probe individual molecules,
      there has been an increasing interest in understanding the mechanisms by which
      motor proteins convert chemical energy into mechanical work. Here we present a
      mathematical model for the chemistry and three dimensional mechanics of the
      kinesin motor protein which captures many of the force dependent features of the
      motor. For the elasticity of the tether that attaches cargo to the motor we
      develop a method for deriving the non-linear force-extension relationship from
      optical trap data. For the kinesin heads, cargo, and microscope stage we
      formulate a three dimensional Brownian Dynamics model that takes into account
      excluded volume interactions. To efficiently compute statistics from the model,
      an algorithm is proposed which uses a two step protocol that separates the
      simulation of the mechanical features of the model from the chemical kinetics of
      the model. Using this approach for a bead transported by the motor, the force
      dependent average velocity and randomness parameter are computed and compared
      with the experimental data.

PMID- 16794925
TI  - Type III secretion, contact-dependent model for the intracellular development of
      chlamydia.
AB  - The medically significant genus Chlamydia is a class of obligate intracellular
      bacterial pathogens that replicate within vacuoles in host eukaryotic cells
      termed inclusions. Chlamydia's developmental cycle involves two forms; an
      infectious extracellular form, known as an elementary body (EB), and a non
      infectious form, known as the reticulate body (RB), that replicates inside the
      vacuoles of the host cells. The RB surface is covered in projections that are in
      intimate contact with the inclusion membrane. Late in the developmental cycle,
      these reticulate bodies differentiate into the elementary body form. In this
      paper, we present a hypothesis for the modulation of these developmental events
      involving the contact-dependent type III secretion (TTS) system. TTS surface
      projections mediate intimate contact between the RB and the inclusion membrane.
      Below a certain number of projections, detachment of the RB provides a signal for
      late differentiation of RB into EB. We use data and develop a mathematical model
      investigating this hypothesis. If the hypothesis proves to be accurate, then we
      have shown that increasing the number of inclusions per host cell will increase
      the number of infectious progeny EB until some optimal number of inclusions. For
      more inclusions than this optimum, the infectious yield is reduced because of
      spatial restrictions. We also predict that a reduction in the number of
      projections on the surface of the RB (and as early as possible during
      development) will significantly reduce the burst size of infectious EB particles.
      Many of the results predicted by the model can be tested experimentally and may
      lead to the identification of potential targets for drug design.

PMID- 16794926
TI  - Occupancy modeling of coverage distribution for whole genome shotgun DNA
      sequencing.
AB  - Expected-value models have long provided a rudimentary theoretical foundation for
      random DNA sequencing. Here, we are interested in improving characterization of
      genome coverage in terms of its underlying probability distributions. We find
      that the mathematical notion of occupancy serves as a good model for evolution of
      the coverage distribution function and reveals new insights related to sequence
      redundancy. Established concepts, such as "full shotgun depth," have been assumed
      invariant, but actually depend on project size and decrease over time. For most
      microbial projects, the full shotgun milestone should be revised downward by
      about 30%. Accordingly, many already-completed genomes appear to have been over
      sequenced. Results also suggest that read lengths for emerging high-throughput
      sequencing methods must be increased substantially before they can be considered
      as possible successors to the standard Sanger method. In particular, gains in
      throughput and sequence depth cannot be made to compensate for diminished read
      length. Limits are well approximated by a simple logarithmic equation, which
      should be useful in estimating maximum coverage-based redundancy for future
      projects.

PMID- 16794927
TI  - Macrophage dynamics in diabetic wound dealing.
AB  - Wound healing in diabetes is a complex process, characterised by a chronic
      inflammation phase. The exact mechanism by which this occurs is not fully
      understood, and whilst several treatments for healing diabetic wounds exist, very
      little research has been conducted towards the causes of the extended
      inflammation phase. We describe a mathematical model which offers a possible
      explanation for diabetic wound healing in terms of the distribution of macrophage
      phenotypes being altered in the diabetic patient compared to normal wound repair.
      As a consequence of this, we put forward a suggestion for treatment based on
      rectifying the macrophage phenotype imbalance.

PMID- 16794928
TI  - On the role of schistosome mating structure in the maintenance of drug-resistant
      strains.
AB  - The effects of drug treatment of human hosts on a population of schistosome
      parasites depends on a variety of factors. Previous models have shown that
      multiple strains of drug-resistant parasites are likely to be favored as the
      treatment rate increases. However, such models have neglected to account for the
      complex nature of schistosome mating biology. To more accurately account for the
      biology of these parasites, a simple mating structure is included in a multi
      strain schistosome model, with parasites under the influence of drug treatment of
      their human hosts. Parasites are assumed to pay a cost for drug resistance in
      terms of reduced reproduction and transmission. The dynamics of the parasite
      population are described by a system of homogeneous differential equations, and
      the existence and stability of the exponential solutions for this system are used
      to infer the impact of drug treatment on the maintenance of schistosome genetic
      diversity.

PMID- 16794929
TI  - A mathematical model of integrin-mediated haptotactic cell migration.
AB  - Haptotactic cell migration, a directed response to gradients of cell
      extracellular matrix adhesion, is an important process in a number of biological
      phenomena such as wound healing and tumour cell invasion. Previously,
      mathematical models of haptotaxis have been developed on the premise that cells
      migrate in response to gradients in the density of the extracellular matrix. In
      this paper, we develop a novel mathematical model of haptotaxis which includes
      the adhesion receptors known as integrins and a description of their functional
      activation, local recruitment and protrusion as part of lamellipodia. Through the
      inclusion of integrins, the modelled cell matter is able to respond to a true
      gradient of cell-matrix adhesion, represented by functionally active integrins.
      We also show that previous matrix-mediated models are in fact a subset of the
      novel integrin-mediated models, characterised by specific choices of diffusion
      and haptotaxis coefficients in their model equations. Numerical solutions suggest
      the existence of travelling waves of cell migration that are confirmed via a
      phase plane analysis of a simplified model.

PMID- 16794930
TI  - Optimal control in a model of dendritic cell transfection cancer immunotherapy.
AB  - We construct a population dynamics model of the competition among immune system
      cells and generic tumor cells. Then, we apply the theory of optimal control to
      find the optimal schedule of injection of autologous dendritic cells used as
      immunotherapeutic agent. The optimization method works for a general ODE system
      and can be applied to find the optimal schedule in a variety of medical
      treatments that have been described by a mathematical model.

PMID- 16794931
TI  - Modeling brain energy metabolism and function: a multiparametric monitoring
      approach.
AB  - Mathematical modeling of brain function is an important tool needed for a better
      understanding of experimental results and clinical situations. In the present
      study, we are constructing and testing a mathematical model capable of simulating
      changes in brain energy metabolism that develop in real time under various
      pathophysiological conditions. The model incorporates the following parameters:
      cerebral blood flow, partial oxygen pressure, mitochondrial NADH redox state, and
      extracellular potassium. Accordingly, all the model variables are only time
      dependent (;point-model' approach). Numerical runs demonstrate the ability of the
      model to mimic pathological conditions, such as complete and partial ischemia,
      cortical spreading depression under normoxic and partial ischemic conditions.
      They also show that, when properly tuned, a model of this type permits the
      monitoring of only one or two crucial variables and the computation of the
      remaining variables in real time during clinical or experimental procedures.

PMID- 16794932
TI  - Modeling the role of diffusion coefficients on Turing instability in a reaction
      diffusion prey-predator system.
AB  - The paper is concerned with the effect of variable dispersal rates on Turing
      instability of a non-Lotka-Volterra reaction-diffusion system. In ecological
      applications, the dispersal rates of different species tends to oscillate in
      time. This oscillation is modeled by temporal variation in the diffusion
      coefficient with large as well as small periodicity. The case of large
      periodicity is analyzed using the theory of Floquet multipliers and that of the
      small periodicity by using Hill's equation. The effect of such variation on the
      resulting Turing space is studied. A comparative analysis of the Turing spaces
      with constant diffusivity and variable diffusivities is performed. Numerical
      simulations are carried out to support analytical findings.

PMID- 16794933
TI  - Model-based analysis of mechanisms responsible for sleep-induced carbon dioxide
      differences.
AB  - This work describes a comprehensive mathematical model of the human respiratory
      control system which incorporates the central mechanisms for predicting sleep
      induced changes in chemical regulation of ventilation. The model integrates four
      individual compartments for gas storage and exchange, namely alveolar air,
      pulmonary blood, tissue capillary blood, body tissues, and gas transport between
      them. An essential mechanism in the carbon dioxide transport is its dissociation
      into bicarbonate and acid, where a buffering mechanism through hemoglobin is used
      to prevent harmfully low pH levels. In the current model, we assume high oxygen
      levels and consider intracellular hydrogen ion concentration as the principal
      respiratory control variable. The resulting system of delayed differential
      equations is solved numerically. With an appropriate choice of key parameters,
      such as velocity of blood flow and gain of a non-linear controller function, the
      model provides steady-state results consistent with our experimental observations
      measured in subjects across sleep onset. Dynamic predictions from the model give
      new insights into the behaviour of the system in subjects with different
      buffering capacities and suggest novel hypotheses for future experimental and
      clinical studies.

PMID- 16794935
TI  - A sufficient condition for reducing recursions in hidden Markov models.
AB  - In hidden Markov models, the probability of observing a set of strings can be
      computed using recursion relations. We construct a sufficient condition for
      simplifying the recursion relations for a certain class of hidden Markov models.
      If the condition is satisfied, then one can construct a reduced recursion where
      the dependence on Markov states completely disappears. We discuss a specific
      example--namely, statistical multiple alignment based on the TKF-model--in which
      the sufficient condition is satisfied.

PMID- 16794934
TI  - Analytical study of the multiplicity of regulatory mechanisms in the tryptophan
      operon.
AB  - In this paper we study the stability of a previously introduced model for the
      tryptophan operon regulatory pathway. For this, we make use of the second
      Lyapunov's method. The results obtained for the wild-type and for a couple ofin
      silico mutant bacterial strains allow a deeper understanding of the multiplicity
      of regulatory mechanisms in this operon. In particular, we confirm that enzyme
      inhibition and transcription attenuation strengthen the system stability, the
      effect of transcription attenuation being much shorter than that of enzyme
      inhibition. Furthermore, the analysis here presented provides some insights about
      how enzyme inhibition affects the system stability.

PMID- 16794936
TI  - Requirements on models and models of active transport of ions in biomembranes.
AB  - Requirements on models of the active transport of ions in biomembranes have been
      formulated. The basic requirements include an explicit dependence of the resting
      potential and intracellular concentrations of ions on the difference of ATP-ADP
      chemical potentials, a consideration of the reversibility of the ionic pump
      operation, a correlation between theoretical and experimental data on the resting
      potential and intracellular concentrations of ions for different types of cells,
      the pump efficiency approaching 100%, and a tendency of the resting potential to
      the Donnan potential if the active transport is blocked. A model satisfying the
      aforementioned requirements has been proposed by the authors as an example.

PMID- 16794937
TI  - A model of spatial epidemic spread when individuals move within overlapping home
      ranges.
AB  - One of the central goals of mathematical epidemiology is to predict disease
      transmission patterns in populations. Two models are commonly used to predict
      spatial spread of a disease. The first is the distributed-contacts model, often
      described by a contact distribution among stationary individuals. The second is
      the distributed-infectives model, often described by the diffusion of infected
      individuals. However, neither approach is ideal when individuals move within home
      ranges. This paper presents a unified modeling hypothesis, called the restricted
      movement model. We use this model to predict spatial spread in settings where
      infected individuals move within overlapping home ranges. Using mathematical and
      computational approaches, we show that our restricted-movement model has three
      limits: the distributed-contacts model, the distributed-infectives model, and a
      third, less studied advective distributed-infectives limit. We also calculate
      approximate upper bounds for the rates of an epidemic's spatial spread.
      Guidelines are suggested for determining which limit is most appropriate for a
      specific disease.

PMID- 16794938
TI  - Stochastic models for mainland-island metapopulations in static and dynamic
      landscapes.
AB  - This paper has three primary aims: to establish an effective means for modelling
      mainland-island metapopulations inhabiting a dynamic landscape; to investigate
      the effect of immigration and dynamic changes in habitat on metapopulation patch
      occupancy dynamics; and to illustrate the implications of our results for
      decision-making and population management. We first extend the mainland-island
      metapopulation model of Alonso and McKane [Bull. Math. Biol. 64:913-958, 2002] to
      incorporate a dynamic landscape. It is shown, for both the static and the dynamic
      landscape models, that a suitably scaled version of the process converges to a
      unique deterministic model as the size of the system becomes large. We also
      establish that, under quite general conditions, the density of occupied patches,
      and the densities of suitable and occupied patches, for the respective models,
      have approximate normal distributions. Our results not only provide us with
      estimates for the means and variances that are valid at all stages in the
      evolution of the population, but also provide a tool for fitting the models to
      real metapopulations. We discuss the effect of immigration and habitat dynamics
      on metapopulations, showing that mainland-like patches heavily influence
      metapopulation persistence, and we argue for adopting measures to increase
      connectivity between this large patch and the other island-like patches. We
      illustrate our results with specific reference to examples of populations of
      butterfly and the grasshopper Bryodema tuberculata.

PMID- 16794939
TI  - Density-dependent migration and synchronism in metapopulations.
AB  - A spatially explicit metapopulation model with density-dependent dispersal is
      proposed in order to study the stability of synchronous dynamics. A stability
      criterion is obtained based on the computation of the transversal Liapunov number
      of attractors on the synchronous invariant manifold. We examine in detail a
      special case of density-dependent dispersal rule where migration does not occur
      if the patch density is below a certain critical density, while the fraction of
      individuals that migrate to other patches is kept constant if the patch density
      is above the threshold level. Comparisons with density-independent migration
      models indicate that this simple density-dependent dispersal mechanism reduces
      the stability of synchronous dynamics. We were able to quantify exactly this loss
      of stability through the frequency that synchronous trajectories are above the
      critical density.

PMID- 16794940
TI  - Identifying environmental determinants of diurnal distribution in marine birds
      and mammals.
AB  - Marine birds and mammals move between various habitats during the day as they
      engage in behaviors related to resting, sleeping, preening, feeding, and
      breeding. The per capita rates of movement between these habitats, and hence the
      habitat occupancy dynamics, often are functions of environmental variables such
      as tide height, solar elevation, wind speed, and temperature. If the system
      recovers rapidly after disturbance, differential equation models of occupancy
      dynamics can be reduced to algebraic equations on two time scales. Identification
      of environmental factors that influence movement between habitats requires time
      series census data collected in both the absence and presence of disturbance.

PMID- 16794941
TI  - A note on the local current associated with the rising phase of a propagating
      impulse in nonmyelinated nerve fibers.
AB  - To extend our recent paper dealing with the cable properties and the conduction
      velocity of nonmyelinated nerve fibers (Bull. Math. Biol. 64, 1069; 2002), the
      behavior of the local current associated with the rising phase of a propagating
      action potential is discussed. It is shown that the process of charging the
      membrane capacity by means of the local current plays a crucial role in
      determining the velocity of nerve conduction. The symmetry of the local current
      with respect to the boundary between the resting and active regions of the nerve
      fiber is emphasized. It is noted that there are several simple quantitative rules
      governing the intensities of the capacitive, resistive and total membrane
      currents observed during the rising phase of an action potential.

PMID- 16794942
TI  - A comparison of continuous and discrete-time West Nile virus models.
AB  - The first recorded North American epidemic of West Nile virus was detected in New
      York state in 1999, and since then the virus has spread and become established in
      much of North America. Mathematical models for this vector-transmitted disease
      with cross-infection between mosquitoes and birds have recently been formulated
      with the aim of predicting disease dynamics and evaluating possible control
      methods. We consider discrete and continuous time versions of the West Nile virus
      models proposed by Wonham et al. [Proc. R. Soc. Lond. B 271:501-507, 2004] and by
      Thomas and Urena [Math. Comput. Modell. 34:771-781, 2001], and evaluate the basic
      reproduction number as the spectral radius of the next-generation matrix in each
      case. The assumptions on mosquito-feeding efficiency are crucial for the basic
      reproduction number calculation. Differing assumptions lead to the conclusion
      from one model [Wonham, M.J. et al., [Proc. R. Soc. Lond. B] 271:501-507, 2004]
      that a reduction in bird density would exacerbate the epidemic, while the other
      model [Thomas, D.M., Urena, B., Math. Comput. Modell. 34:771-781, 2001] predicts
      the opposite: a reduction in bird density would help control the epidemic.

PMID- 16794943
TI  - Mathematical models for hantavirus infection in rodents.
AB  - Hantavirus pulmonary syndrome is an emerging disease of humans that is carried by
      wild rodents. Humans are usually exposed to the virus through geographically
      isolated outbreaks. The driving forces behind these outbreaks is poorly
      understood. Certainly, one key driver of the emergence of these viruses is the
      virus population dynamics within the rodent population. Two new mathematical
      models for hantavirus infection in rodents are formulated and studied. The new
      models include the dynamics of susceptible, exposed, infective, and recovered
      male and female rodents. The first model is a system of ordinary differential
      equations while the second model is a system of stochastic differential
      equations. These new models capture some of the realistic dynamics of the
      male/female rodent hantavirus interaction: higher seroprevalence in males and
      variability in seroprevalence levels.

PMID- 16794944
TI  - Modeling the HIV/AIDS epidemic among injecting drug users and sex workers in
      Kunming, China.
AB  - This paper presents a mathematical model of the HIV/AIDS epidemic in Kunming, the
      provincial capital of Yunnan, China. The population is divided into several
      groups, with individuals possibly changing group. Two transmission routes of HIV
      are considered: needle sharing between injecting drug users (IDUs) and commercial
      sex between female sex worker (FSWs) and clients. The model includes male IDUs
      who are also clients and female IDUs who are also FSWs. Groups are split in two-
      risky and safe--according to condom use and needle sharing. A system of partial
      differential equations is derived to describe the spread of the disease. For the
      simulation, parameters are chosen to fit as much as possible data publicly
      available for Kunming. Some mathematical properties of the model--in particular
      the epidemic threshold R0 which determines the goal of public health
      interventions--are also presented. Though the model couples two transmission
      routes of HIV, the approximation R0 approximately = max[R0(IDU), R0(sex)], with
      closed formulas for R0(IDU) and R0(sex), appears to be quite good. The critical
      levels of condom use and clean needle use necessary to stop both the sexual
      transmission and the transmission among IDUs can therefore be determined
      independently.

PMID- 16794945
TI  - Basic reproduction number for HIV model incorporating commercial sex and behavior
      change.
AB  - The basic reproduction number is obtained for an HIV epidemic model incorporating
      direct and indirect commercial sex as well as behavior change by the female
      commercial sex workers (CSWs) and their male customers in response to the
      proliferation of the disease in the community. A recent result by van den
      Driessche P., and Watmough J. (Math. Biosci. 180:29-48, 2002) is utilized to
      compute the threshold parameters for the local asymptotic stability of the
      Disease-Free Equilibrium (DFE), by considering the transfers in and out of the
      infective classes. Numerical examples are used to describe the uniqueness and
      global properties of the endemic equilibrium when DFE is unstable. Biological
      interpretation of the results obtained in this work is discussed, as are the
      implications of our results for the design of public health policies such as
      targeting strategy to target intervention and control measures toward specific
      high-risk population groups in order to reduce infections. We show that targeting
      any one sector of the commercial sex alone for prevention will be difficult to
      have a decided effect on eradicating the epidemic. However, if the aim of the
      targeted intervention policy is not eradication of the epidemic but decrease in
      HIV incidence of a particular high-risk group, then concentrated targeting
      strategy could be sufficient, if properly implemented. This work also
      demonstrates the usefulness of the theorem of van den Driessche and Watmough
      (Math. Biosci. 180:29-48, 2002) in obtaining threshold parameters for complicated
      infectious diseases models.

PMID- 16794946
TI  - Theoretical assessment of public health impact of imperfect prophylactic HIV-1
      vaccines with therapeutic benefits.
AB  - This paper presents a number of deterministic models for theoretically assessing
      the potential impact of an imperfect prophylactic HIV-1 vaccine that has five
      biological modes of action, namely "take," "degree," "duration,"
      "infectiousness," and "progression," and can lead to increased risky behavior.
      The models, which are of the form of systems of nonlinear differential equations,
      are constructed via a progressive refinement of a basic model to incorporate more
      realistic features of HIV pathogenesis and epidemiology such as staged
      progression, differential infectivity, and HIV transmission by AIDS patients. The
      models are analyzed to gain insights into the qualitative features of the
      associated equilibria. This allows the determination of important epidemiological
      thresholds such as the basic reproduction numbers and a measure for vaccine
      impact or efficacy. The key findings of the study include the following (i) if
      the vaccinated reproduction number is greater than unity, each of the models
      considered has a locally unstable disease-free equilibrium and a unique endemic
      equilibrium; (ii) owing to the vaccine-induced backward bifurcation in these
      models, the classical epidemiological requirement of vaccinated reproduction
      number being less than unity does not guarantee disease elimination in these
      models; (iii) an imperfect vaccine will reduce HIV prevalence and mortality if
      the reproduction number for a wholly vaccinated population is less than the
      corresponding reproduction number in the absence of vaccination; (iv) the
      expressions for the vaccine characteristics of the refined models take the same
      general structure as those of the basic model.

PMID- 16794947
TI  - Lyapunov functions and global stability for SIR and SIRS epidemiological models
      with non-linear transmission.
AB  - Lyapunov functions for two-dimension SIR and SIRS compartmental epidemic models
      with non-linear transmission rate of a very general form f(S, I) constrained by a
      few biologically feasible conditions are constructed. Global properties of these
      models including these with vertical and horizontal transmission, are thereby
      established. It is proved that, under the constant population size assumption,
      the concavity of the function f(S, I) with respect to the number of the infective
      hosts I ensures the uniqueness and the global stability of the positive endemic
      equilibrium state.

PMID- 16794948
TI  - Convection effects in the BIAcore dextran layer: surface reaction model.
AB  - The BIAcore is a surface plasmon resonance (SPR) device used to measure rate
      constants, primarily for biochemical reactions. It consists of a flow channel
      containing one reactant adjoining a dextran gel containing the other. In order to
      explain anomalous measurements from the device, it has been proposed that some
      flow penetrates into the dextran layer, thus enhancing transport. A model is
      presented that accounts for such behavior, and typical velocity fields in the
      dextran are constructed. The system is analyzed in the limit of the surface
      reaction model, which corresponds to the limit of thin dextran layers. Asymptotic
      and singular perturbation techniques are used to analyze association and
      dissociation kinetics. Linear and nonlinear integral equations result from the
      analysis; explicit and asymptotic solutions are constructed for physically
      realizable cases. The results indicate that the effects of such penetration are
      bound to be small, regardless of the flow model used.

PMID- 16794949
TI  - Evolution of dispersal in a structured metapopulation model in discrete time.
AB  - In this article, a structured metapopulation model in discrete time with
      catastrophes and density-dependent local growth is introduced. The fitness of a
      rare mutant in an environment set by the resident is defined, and an efficient
      method to calculate fitness is presented. With this fitness measure evolutionary
      analysis of this model becomes feasible. This article concentrates on the
      evolution of dispersal. The effect of catastrophes, dispersal cost, and local
      dynamics on the evolution of dispersal is investigated. It is proved that without
      catastrophes, if all population-dynamical attractors are fixed points, there will
      be selection for no dispersal. A new mechanism for evolutionary branching is also
      found: Even though local population sizes approach fixed points, catastrophes can
      cause enough temporal variability, so that evolutionary branching becomes
      possible.

PMID- 16794950
TI  - Generality of the final size formula for an epidemic of a newly invading
      infectious disease.
AB  - The well-known formula for the final size of an epidemic was published by Kermack
      and McKendrick in 1927. Their analysis was based on a simple susceptible-infected
      recovered (SIR) model that assumes exponentially distributed infectious periods.
      More recent analyses have established that the standard final size formula is
      valid regardless of the distribution of infectious periods, but that it fails to
      be correct in the presence of certain kinds of heterogeneous mixing (e.g., if
      there is a core group, as for sexually transmitted diseases). We review previous
      work and establish more general conditions under which Kermack and McKendrick's
      formula is valid. We show that the final size formula is unchanged if there is a
      latent stage, any number of distinct infectious stages and/or a stage during
      which infectives are isolated (the durations of each stage can be drawn from any
      integrable distribution). We also consider the possibility that the transmission
      rates of infectious individuals are arbitrarily distributed--allowing, in
      particular, for the existence of super-spreaders--and prove that this potential
      complexity has no impact on the final size formula. Finally, we show that the
      final size formula is unchanged even for a general class of spatial contact
      structures. We conclude that whenever a new respiratory pathogen emerges, an
      estimate of the expected magnitude of the epidemic can be made as soon the basic
      reproduction number R0 can be approximated, and this estimate is likely to be
      improved only by more accurate estimates of R0, not by knowledge of any other
      epidemiological details.

PMID- 16794951
TI  - Fuzzy polynucleotide spaces and metrics.
AB  - The study of genetic sequences is of great importance in biology and medicine.
      Mathematics is playing an important role in the study of genetic sequences and,
      generally, in bioinformatics. In this paper, we extend the work concerning the
      Fuzzy Polynucleotide Space (FPS) introduced in Torres, A., Nieto, J.J., 2003. The
      fuzzy polynucleotide Space: Basic properties. Bioinformatics 19(5); 587-592 and
      Nieto, J.J., Torres, A., Vazquez-Trasande, M.M. 2003. A metric space to study
      differences between polynucleotides. Appl. Math. Lett. 27:1289-1294: by studying
      distances between nucleotides and some complete genomes using several metrics. We
      also present new results concerning the notions of similarity, difference and
      equality between polynucleotides. The results are encouraging since they
      demonstrate how the notions of distance and similarity between polynucleotides in
      the FPS can be employed in the analysis of genetic material.

PMID- 16794952
TI  - Why is the number of DNA bases 4?
AB  - In this paper we construct a mathematical model for DNA replication based on
      Shannon's mathematical theory for communication. We treat DNA replication as a
      communication channel. We show that the mean replication rate is maximal with
      four nucleotide bases under the primary assumption that the pairing time of the G
      C bases is between 1.65 and 3 times the pairing time of the A-T bases.

PMID- 16794953
TI  - Recovery and characterization of a 30.7-kDa protein from Bacillus licheniformis
      associated with inhibitory activity against methicillin-resistant Staphylococcus
      aureus, vancomycin-resistant enterococci, and Listeria monocytogenes.
AB  - Of 131 bacterial isolates from seaweed, a culture of Bacillus licheniformis
      produced a novel protein with antibacterial activity against methicillin
      resistant Staphylococcus aureus, vancomycin-resistant enterococci, and Listeria
      monocytogenes. The antibacterial activity was maximal in cultures prepared in
      Columbia broth containing pieces of synthetic polyurethane sponge and shaken at
      210 to 230 rpm. Antibacterial activity was not found in cultures grown statically
      or with different speeds of rotary shaking. Reduced activity was apparent in
      supernatants prepared from marine 2216E broth and tryptone soya broth with or
      without 1% (wt/vol) sodium chloride. The antibacterial compound was sensitive to
      proteinase K, pronase, and trypsin, but was not affected by Tween-20, -40, -60,
      or -80, or alpha- or beta-amylase. Activity was not adversely affected by heating
      up to 40 degrees C or treatment at pH 5 to 14. The bioactive compound was
      determined to be associated with a protein of 30.7 kDa, which had homology to the
      YbdN protein of B. licheniformis ATCC 14580.

PMID- 16794954
TI  - Discovery of the genes in response to white spot syndrome virus (WSSV) infection
      in Fenneropenaeus chinensis through cDNA microarray.
AB  - We used microarray technology to study differentially expressed genes in white
      spot syndrome virus (WSSV)-infected shrimp. A total of 3136 cDNA targets,
      including 1578 unique genes from a cephalothorax cDNA library and 1536 cDNA
      clones from reverse and forward suppression subtractive hybridization (SSH)
      libraries of Fenneropenaeus chinensis, plus 14 negative and 8 blank control
      clones, were spotted onto a 18 x 18 mm area of NH(2)-modified glass slides. Gene
      expression patterns in the cephalothorax of shrimp at 6 h after WSSV injection
      and moribund shrimp naturally infected by WSSV were analyzed. A total of 105
      elements on the arrays showed a similar regulation pattern in artificially
      infected shrimp and naturally infected moribund shrimp; parts of the results were
      confirmed by semiquantitative reverse transcriptase-polymerase chain reaction (RT
      PCR). The up-regulated expression of immune-related genes, including heat shock
      proteins (HSP70 and HSP90), trehalose-phosphate synthase (TPS), ubiquitin C, and
      so forth, were observed when shrimp were challenged with WSSV. Genes including
      myosin LC2, ATP synthase A chain, and arginine kinase were found to be down
      regulated after WSSV infection. The expression of housekeeping genes such as
      actin, elongation factor, and tubulin is not stable, and so these genes are not
      suitable as internal standards for semiquantitative RT-PCR when shrimp are
      challenged by WSSV. As a substitute, we found that triosephosphate isomerase
      (TPI) was an ideal candidate of interstandards in this situation.

PMID- 16794955
TI  - [Topography and morphometry of the porus trigeminus].
AB  - BACKGROUND AND PURPOSE: The trigeminal nerve passes from the posterior to the
      middle cranial fossa above the superior edge of the petrous part and below
      attachment of the tentorium cerebelli. Behind this place it is surrounded by the
      dural trigeminal cave which opens posteriorly as the porus trigeminus. The aim of
      this study was to describe the porus trigeminus along with its relation to the
      trigeminal nerve and selected structures around. MATERIAL AND METHODS: The study
      was performed on the material of 20 human, formalin fixed specimens of the
      cranial base. Measurements were taken with a surgical microscope with an ocular
      ruler, with precision of 0.2 mm. RESULTS: Mean width of the porus was 7.3 (+/
      1.0) mm and height 2.2 (+/-0.4) mm. Dimensions of the trigeminal nerve within the
      porus were 5.8 (+/-0.8) mm and 2.1 (+/-0.4) mm, respectively. The porus is
      surrounded by shallow ellipsoid hollow measuring 12.1 (+/-1.8) over 5.1 (+/-1.1)
      mm. Relation of the porus to the petrous vein was described, as well as to other
      veins emptying to the dural sinuses in its vicinity. Distances between the porus
      and venous dural openings were very variable. The following distances were
      measured from the porus trigeminus to: the internal acustic porus [6.6 (+/-1.7)
      mm], jugular foramen [16.2 (+/-1.8) mm], jugular tubercle [18.9 (+/-1.8) mm],
      abducent nerve [5.9 (+/-1.2) mm], trochlear nerve [4.6 (+/-1.4) mm], oculomotor
      nerve [8.4 (+/-1.9) mm], posterior clinoid process [14.7 (+/-1.8) mm] and median
      plane [left 13.7 (+/-1.0), and right 13.5 (+/-1.9) mm]. CONCLUSIONS: Obtained
      results may be helpful during planning surgical approaches to the Meckel's cave
      and petroclival region.

PMID- 16794956
TI  - [Stereotactic ventrolateral thalamotomy in the treatment of essential tremor].
AB  - BACKGROUND AND PURPOSE: Essential tremor is the most common tremorogenic movement
      disorder. In the majority of patients the progression of the disease is slow and
      the pharmacological treatment effectively alleviates tremor. In rare cases of
      increased essential tremor the surgical treatment (ventrolateral thalamotomy) is
      indicated. The goal of this study was to assess the effectiveness of unilateral
      thalamotomy in the treatment of essential tremor. MATERIAL AND METHODS: 10
      stereotactic ventrolateral thalamotomies were performed in 9 patients for
      pharmacologically intractable essential tremor. Right thalamotomy was done in 5
      patients and left thalamotomy in 4 patients. The study included five men and four
      women. Patients were assessed according to the Clinical Rating Scale for Tremor
      (CRST) before surgery and at 3, 12 and 24 months after thalamotomy. RESULTS: In
      the postoperative period there was a marked reduction of essential tremor in the
      contralateral arm and, to a lower extent, in the contralateral leg. The mean
      presurgery value for contralateral upper extremity postural tremor (scores 5/6
      CRST) decreased from 3.5 to mean postsurgery value of 0.6. The tremor reduction
      contributed to 59% improvement in specific motor tasks of upper extremities (Part
      B of CRST) at 2 years follow-up. There was also improvement of functional
      disabilities (Part C of CRST) by 62% when compared to preoperative value 2 years
      postoperatively. CONCLUSIONS: Ventrolateral thalamotomy is a highly effective
      method in the treatment of essential tremor. The side effects related to surgery
      are rare and most of them are transient.

PMID- 16794957
TI  - [Stereotactic pallidotomy and thalamotomy in the treatment of primary dystonia].
AB  - BACKGROUND AND PURPOSE: The goal of the study was to assess the results of the
      stereotactic pallidotomy and thalamotomy in the treatment of primary dystonia.
      MATERIAL AND METHODS: Thirty patients with primary dystonia underwent twenty
      eight stereotactic pallidotomies and twenty two thalamotomies. The operations
      were based on the fused images of computed tomography and magnetic resonance
      imaging, and were verified by an intraoperative neurophysiological investigation.
      Neurological and neuropsychological assessments were performed before surgery and
      at 3 days, 3 and 6 months after the operation. The Mann-Whitney U test was used
      to find out statistic differences between subgroups and the Wilcoxon test to
      compare results between particular assessments. RESULTS: The statistic analysis
      showed postsurgical amelioration of the neurological state lasting at least 6
      months. A better long-term outcome was revealed in the subgroup of pallidotomies
      vs. thalamotomies, in the subgroup with the onset of dystonia after the age of 35
      vs. earlier onset, and in the subgroup of the focal and local dystonia vs.
      generalized dystonia. The statistically significant improvement was achieved at a
      depression level and the statistically significant deterioration was not stated
      in the mental status after the operations. A very low percentage of neurological
      complications after the operations was found in the study. CONCLUSIONS: The
      stereotactic pallidotomies and thalamotomies are effective and safe options in
      the treatment of the intractable cases of primary dystonia. Both resulted
      predominantly in contralateral improvement of motor functions. However, the
      results of pallidotomies are better than thalamotomies six months after the
      surgery. The improvement of the mood without cognitive deterioration was revealed
      in the neuropsychological tests after the operations. Only few, persistent and
      mild complications were ascertained in the study.

PMID- 16794958
TI  - [Results of 13 hypoglosso-facial anastomoses].
AB  - BACKGROUND AND PURPOSE: Facial nerve paralysis significantly decreases the
      quality of life in patients after skull base tumors surgery. There are different
      options for surgical repair of the nerve. One of the most effective methods is
      the anastomosis of the distal trunk of the facial nerve with the proximal trunk
      of the hypoglossal nerve or with hypoglossal loop. MATERIAL AND METHODS: Thirteen
      hypoglosso-facial anastomoses had been performed in our department between 1999
      and 2003. In all patients the facial nerve paralysis was due to the surgery in
      its proximity. In one case the patient suffered from petroclival chordoma, in one
      case ameloblastoma, one was with petroclival meningioma and the rest of cases
      were after vestibular schwannoma. The follow-up period lasted from 6 months to
      three years. The final result was expressed in House-Brackmann scale (HB)
      describing facial muscle strength. RESULTS: In two cases there was no improvement
      (HB 6), in two cases barely perceptible motion (HB 5), in five obvious weekness
      with disfiguring assymetry (HB 4) and in four obvious but not disfiguring
      dysfunction (HB 3). There was only one postoperative complication haematoma at
      the place of anastomosis requiring evacuation. CONCLUSION: Hypoglosso-facial
      anastomosis remains one of the most important techniques of the reanimation of
      the paralysed face. Its efficacy is limited, but it is a relatively safe
      procedure.

PMID- 16794959
TI  - [Percutaneous ventriculoatrial shunt: experience with 179 cases].
AB  - BACKGROUND AND PURPOSE: The aim of the study was to assess the impact of
      percutaneous placement of a distal catheter on treatment results in patients with
      hydrocephalus undergoing ventriculoatrial shunt (VA) implantation. MATERIAL AND
      METHODS: This retrospective study included 184 patients aged 14-80 years (mean:
      48 yrs) with hydrocephalus who were treated with VA shunt between 1990-2003. In
      179 patients the cardiac catheter was introduced by catheterization of the
      internal jugular vein, rarely the subclavian or external jugular vein, using the
      Seldinger technique and standard equipment for central vein catheterization. The
      mean follow-up time was 64 months. RESULTS: The most frequent complication
      related to the method used was an incidental puncture of the carotid artery (5%
      of cases). Pneumothorax was observed in two cases. None of these complications
      caused permanent sequelae. Early (<6 months) postoperative complications included
      shunt infection in the neck region (2 cases), impatience of the cardiac catheter
      (3), disconnection between the outlet and the cardiac catheter with its
      subsequent migration (1) and kinking of the distal catheter (1). Late (>6 months)
      complications included infection along the distal catheter (2 cases), occlusion
      of the cardiac catheter (4) and its disconnection (1). The mean duration of the
      procedure was 40 minutes. CONCLUSIONS: Percutaneous placement of the cardiac
      catheter is a safe procedure which shortens the duration of the operation and
      minimizes tissue traumatization. This method may contribute to a decreased risk
      of infection. VA shunt with presented modification may be used in those patients
      for whom implantation of ventriculoperitoneal shunt is contraindicated.

PMID- 16794960
TI  - [Deep brain stimulation in the management of Parkinson's disease].
AB  - Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease
      and other movement disorders. This surgical technique is applied to three brain
      targets: the ventral intermediate nucleus of the thalamus (Vim), the globus
      pallidus internus (Gpi) and the subthalamic nucleus (STN). Vim DBS improves
      contralateral parkinsonian tremor. STN and GPi DBS improve contralateral
      bradykinesia, rigidity, parkinsonian tremor and also levodopa-induced dyskinesia.
      There is little comparative data between bilateral STN and bilateral GPi
      procedures but the improvement with bilateral STN DBS seems more pronounced than
      with bilateral GPi DBS. Moreover, only STN BDS allows a significant decrease of
      antiparkinsonian medication. The other advantage of STN over GPi DBS is the lower
      consumption of current. The DBS procedure contrary to ablative surgery has the
      unique advantage of reversibility and adjustability over time. Patients with no
      behavioral, mood and cognitive impairments benefit the most from bilateral STN
      DBS. The stimulation-induced adverse effects related to DBS are reversible and
      adjustable. More specific adverse effects related do hardware are: disconnection,
      lead breaking, erosion or infection. The disadvantage of DBS is a relatively high
      cost. The setting of stimulation parameters to achieve the best clinical result
      may be very time-consuming. Most authors agree that DBS is a safer and more
      favorable procedure than ablative surgery.

PMID- 16794961
TI  - [Recent advances in molecular biology of central nervous system embryonal tumors
      and development of potential molecular targeted therapies].
AB  - Embryonal tumours constitute the largest group of malignant pediatric brain
      tumours. Their origin and histological classification is debated. Diagnosis is
      controversial and patients' response to therapy on the basis of morphologic
      appearance alone, is difficult to predict. Therefore accurate clinical staging
      remains a critical component of clinical management. In recent years real
      progress has been made in our understanding of the molecular genetic
      abnormalities that govern the initiation and/or progression of embryonal tumours.
      This review is focused on the principal molecular genetic abnormalities so far
      identified in embryonal brain tumours and discusses their possible biological and
      clinical applications in developing a molecular risk staging system which
      hopefully will lead to the molecular targeted therapies, curative non-toxic
      treatment for all children.

PMID- 16794962
TI  - [Is the inhibition of adenosine A(2A) receptors an efficient way of Parkinson's
      disease treatment?].
AB  - The authors intended to focus the attention of the medical community on the
      potential therapeutic usefulness of A(2A) adenosine receptors antagonists in the
      treatment of Parkinson's disease. Basal ganglia express a big amount of A(2A)
      adenosine receptors, occurring mainly on the external surfaces of neurons located
      at indirect pathways between the striatum, globus pallidus and substantia nigra.
      Experiments with the animal models of Parkinson's disease indicate that A(2A)
      receptors are strongly involved in the regulation of the central movement system.
      Co-localization of A(2A) and dopaminergic D2 receptors in the striatum creates a
      milieu for an antagonistic interaction between adenosine and dopamine. The
      experimental data prove that the best mobility improvement of patients with
      Parkinson's disease could be achieved with a simultaneous activation of
      dopaminergic D2 receptors and inhibition of adenosine A(2A) receptors. In animal
      models of Parkinson's disease, the use of selective antagonists of A(2A)
      receptors, such as istradefylline, led to the reversibility of movement
      dysfunction. These compounds might improve the mobility during both monotherapy
      and co-administration with L-dopa and the dopamine receptor agonists. The use of
      these antagonists in the combined therapy enables the reduction of the L-dopa
      doses, as well as reduction of the side effects. In the adjunctive therapy, the
      A(2A) antagonists might be used in both moderate and advanced stages of
      Parkinson's disease. The long-lasting administration of the A(2A) receptor
      antagonists does not decrease patient's response and does not cause side effects
      typical of the L-dopa therapy. It was proved on different animal models that
      inhibition of A(2A) receptors not only decreases the movement disturbance, but
      also reveals the neuroprotective activity, which might slow down or stop the
      progress of the disease.

PMID- 16794963
TI  - [Cerebral aneurysms in patients with the occlusion of the brachiocephalic
      vessels].
AB  - Cerebral aneurysms coexistent with iatrogenic (after surgical ligation or
      occlusion) or idiopathic (due to atheromatosis) occlusion of an extracranial
      cerebral artery are very rare. The occlusion of the brachiocephalic vessels leads
      to the formation of a collateral circulation at two levels: the circle of Willis
      and the connections between collaterals of the extracranial cerebral arteries.
      The authors discuss different types of collateral arterial pathways as well as
      hemodynamic abnormalities in the case of the occlusion of the brachiocephalic
      vessels, particularly internal carotid artery or the innominate artery occlusion.
      The paper analyses the etiopathogenesis of cerebral aneurysms in view of the
      hemodynamic theory of cerebral aneurysms formation. The article is illustrated
      with own three cases of ruptured cerebral aneurysms coexistent with the occlusion
      of the innominate artery.

PMID- 16794964
TI  - [Niemann-Pick disease, type A: a case report].
AB  - Niemann-Pick disease (NPD) type A is a rapidly developing metabolic illness, with
      autosomal recessive mode of inheritance. A deficiency of the lysosomal enzyme-
      acid sphingomyelinase (ASM) produces the clinical phenotype with multiple organ
      involvement including the central nervous system. Type A NPD is characterized by
      failure to thrive, hepatosplenomegaly and rapidly progressive neurodegenerative
      course that leads to death by the age of 2-3 years. The authors report a 3-year
      old boy with fatal course of the disease.

PMID- 16794965
TI  - [A case of the Lambert-Eaton syndrome of non-neoplastic origin. Ten-year follow
      up].
AB  - A case is presented of a 34-year-old man who developed weakness of the proximal
      muscles of the extremities, particularly lower, slight myalgia, and vegetative
      symptoms (dryness in the mouth). Those symptoms progressed within a month. On
      examination weakness of the muscles of the extremities was found as well as weak
      tendon reflexes, slight atrophy of muscles of the arms and thighs and
      apokamnosis. Edrophonium test was slightly positive. Electrostimulation revealed
      changes typical of the Lambert-Eaton syndrome: low amplitude of the compound
      muscle action potential on single stimulus, decreasing amplitude of the
      subsequent responses to 3 Hz stimulation, marked facilitation on 30 Hz
      stimulation. Neoplastic etiology was excluded by chest X-ray and CT, as well as
      by bronchoscopy, abdominal and prostatic USG, and thyroid USG and scintigraphy.
      Antibodies to AChR were not found in the serum. The titre of the antibodies
      against voltage-gated calcium channels was highly positive which was decisive in
      the diagnosing of the Lambert-Eaton syndrome. The patient was treated with
      pyridostigmine, corticosteroids, cyclophosphamide and immunoglobulins. Ten years
      of follow-up have fully confirmed the diagnosis of a non-neoplastic Lambert-Eaton
      syndrome.

PMID- 16794966
TI  - [Giant meningioma of the cranial vault and brain: a report of two cases who had
      not consented for more that 10 years].
AB  - It is extremely rare nowadays to meet the patient with a giant tumour of the
      skull and brain with deformity of the head and who has not consented for any
      treatment for many years. We present two rare cases of large tumours. The first
      case is an example of good prognosis of the surgical procedure despite the
      extensive size of the tumour. The second shows the natural history of the cranial
      vault meningioma not treated for more than 30 years. We assume that frontal lobe
      syndrome was responsible for treatment decisions in both patients.

PMID- 16794967
TI  - [Motor cortex stimulation in the treatment of the central pain: a case report].
AB  - Motor cortex stimulation (MCS) is one of the methods of treatment in chronic pain
      syndromes. According to recent clinical studies effectiveness of this mode of
      treatment in the central pain has been proved. This article reports the first
      case of a patient with the thalamic syndrome treated with MCS in the Clinical
      Department of Neurosurgery in Military Clinical Hospital in Bydgoszcz. The
      procedure of implantation was performed with the guidance of a frameless
      neuronavigation system which served for localization of the precentral gyrus.
      Correct placement of the electrode was confirmed by intraoperative stimulation.
      As a result of the treatment a decrease of pain and improvement of psychosocial
      state has been achieved.

PMID- 16794968
TI  - [Pneumology -- current developments].

PMID- 16794970
TI  - [Stem cells in cardiovascular medicine].

PMID- 16794969
TI  - [Cardiology -- an update].

PMID- 16794971
TI  - [Intensive care medicine: after positive studies questions occur].

PMID- 16794972
TI  - [Nephrology 2005/2006. Recent clinical studies and developments in science].

PMID- 16794973
TI  - [Development of various forms of hypertension and a new assessment of
      antihypertensive medication].

PMID- 16794974
TI  - [Clinical advances in gastroenterology].

PMID- 16794975
TI  - [Clinical advances in "nutritional treatment"].

PMID- 16794976
TI  - [Clinical advances in diabetes].

PMID- 16794977
TI  - [Clinical advances 2006: endocrinology].

PMID- 16794978
TI  - [Acute myeloid leukemia -- on the way towards pathogenesis-oriented treatment].

PMID- 16794979
TI  - [Immunology: new approaches to immuno-modulation and immunotherapy].

PMID- 16794980
TI  - [Infectiology and tropical medicine -- new developments 2006].

PMID- 16794981
TI  - [Neurology: current advances 2006].

PMID- 16794982
TI  - [Clinical pharmacology: knowledge acquired on drugs after their approval].

PMID- 16794983
TI  - [Health care research: the last mile in sight].

PMID- 16794985
TI  - [Quantitative Cardiotocography--what does it look like and what can we expect].
AB  - BACKGROUND: [corrected] Cardiotocography (CTG) seems to be a non-reliable,
      expensive but nevertheless practical method for fetal surveillance. Moreover, its
      diagnostic value is dependent on a long-standing experience of the obstetrician
      (midwife). It is difficult to define exact diagnostic criteria since nearly all
      CTG phenomena are lacking precise qualification by the naked eye. Therefore, the
      idea must be born in mind to analyze fetal heart frequency (FHF) by computer,
      first off-line then on-line, in order to evaluate its true diagnostic power
      objectively. METHODS: The FHF of 583 deliveries terminated by the vaginal route
      were registered prospectively using a PC and an RS422 interface. In 443 cases
      acid-base measurements (ABL 500, RADIOMETER, Copenhagen) in blood of the
      umbilical artery (UA) and vein (UV) were available and plausible. In this study
      only the last 30 min ante-partum were analyzed. The program for FHF analysis was
      written in MATLAB (The Mathworks Inc., USA). A CTG score was developed using
      three components of FHF: basal FHF, the deceleration area of all dips, and the
      micro-fluctuation (MF) of the basal fetal heart rate (FHR). MF denotes the true
      number of "turning-points" per minute of basal FHR. For each component a maximum
      of 6 scoring points could be assigned according to empirical cut-off values.
      These cut-off values were determined using correlation analysis with acid-base
      parameters in UA blood, especially the actual pH. The accordance between score
      and pH values was further demonstrated by assignment of 0.036 pH-units to each of
      the 19 (18 + zero) scoring points, thus covering a pH range between 6.700 and
      7.350 (UA). A resulting variable, delta pH (pH measured, UA-pH assigned) was
      studied and used for further analysis. In order to define criteria for fetal
      mortality in utero only cases with pH, UA between 7.250 and 7.350 were accepted.
      RESULTS: Median basal FHF under normal conditions amounted to 138 bpm (mean: 137
      +/- 14.9) in 4180 minutes of 372 fetuses. 120 bpm equals the 13.4(th) and 160 bpm
      the 94.6(th) centile of the distribution. Given fetal normacidity (UA) MF is
      58/minute and the mean MF 57.9 +/- 13.4, respectively, with a 10 (th) centile of
      41/minute. MF and basal FHF are correlated significantly (r = 0.410, P << 10(
      4)). The declaration-area per fetus is significantly correlated with actual pH
      (UA), r = -0.473, P << 10(-4). the score itself is highly significantly
      correlated with actual pH (UA) (r = -0.559, P << 10(-4)) and the other parameters
      of fetal acid-base balance. Nevertheless, prediction variability for pH,
      especially in score = 1, 2 and zero (minimal CTG pathology) is still present: 80%
      of all predicted pH values lie in between -0.092 and + 0.071. It is strongly
      suggested that this score-related predictive pH variability is caused by maternal
      breathing habits during the last 30 minutes of delivery. CONCLUSION: Adequate
      quantification of only three variables of FHR using a score leads to fairly good
      correlations with parameters of the fetal acid-base balance. Thus actual pH (UA)
      can be predicted in reasonable clinical limits. Still present variability in
      prediction of pH seems to be, in part, of maternal origin. The maternal influence
      could be eliminated by continuous (transcutaneous) monitoring of maternal pCO(2).
      Along these lines the quantitative electronic monitoring of FHR will be realized
      and instrumented (off-line and on-line) by nexus/gmt, Frankfurt, a.M., Germany.

PMID- 16794986
TI  - [Implementation of perinatal regionalization: frequency of high-risk deliveries
      outside of specialized perinatal care centres].
AB  - BACKGROUND: The concentration of high-risk deliveries in specialized perinatal
      care centres contributes to the reduction of infant mortality and morbidity. This
      study investigates the frequency of high-risk deliveries in hospitals with
      inadequate level of perinatal care. METHODS: From the files of a German statutory
      health insurance we draw a random sample of 3.967 women who gave birth april to
      june 2002. The women received a questionnaire and were asked to send in their
      "maternity logbook", a document that every pregnant woman receives and where
      prenatal visits and births are documented by the obstetricians in standardized
      form. From the 1,593 responders (response rate 40.2 %) we selected 559 high-risk
      cases. 83 of these (14.8 %) delivered at a specialized perinatal care centre. The
      remaining 476 deliveries were subjected to an individual analysis of their data.
      Based on published guidelines for antenatal transport and on data about the
      perinatal care facilities of German hospitals the adequacy of the delivery
      hospital was rated for each case. RESULTS: 2.4 % of the whole sample (38/1,503)
      were classified as "inadequate hospital of delivery". 17 of these 38 cases were
      considered as potentially avoidable because significant antepartal risk factors
      were documented. 5 (25 %) of the 20 highest risk cases (twins < 36 weeks of
      gestational age, singletons < 32 weeks, infants < 1.500 g) were classified as
      avoidable referrals to inadequate hospitals. CONCLUSIONS: Regionalization of
      perinatal care must be enhanced by adequate appreciation of antenatal risk
      factors and counselling of pregnant women on the choice of place of delivery.

PMID- 16794987
TI  - [Analysis of the Nuchal Transparency (NT) screening concept at the gynecologocial
      clinic of MHH: a prospective follow-up study].
AB  - BACKGROUND: To date, various and partly competitive screening strategies for the
      risk calculation of trisomy 21 are applied in Germany. The aim of this study was
      to control the published test performance data of different methods in an
      unselected group of patients, thus allowing us to clearly assess the practical
      value of the respective methods. PATIENTS AND METHODS: At the MH Hannover, 744
      women with a singleton pregnancy underwent an NT measurement according to the FMF
      guidelines. Additionally, 590 of these women had a PAPP-A and free ssHCG testing
      in a laboratory accredited by the FMF London. The fetal outcome of all 744
      patients examined was assessed. Based on these data, test performance values were
      calculated for each test strategy under the hypothetical assumption that every
      women would have followed the same screening strategy. RESULTS: Age-related
      screening revealed to have the highest false-positive rate (25 %). Age screening
      combined with serum markers showed to have the highest sensitivity (100 %).
      Screening combining age, NT measurement and serum markers yielded the highest
      specificity (97 %). Combined screening by NT and age achieved the same
      sensitivity as age-related screening with a markedly lower false-positive rate
      than screening combining age and serum markers. Invasive tests were performed in
      11 % of the patients. In 8 % of these, a pathologic karyotype was detected.
      CONCLUSIONS: In comparison to age-related screening, first trimester screening
      allows us to define groups at risk for trisomy 21 more clearly. This seems to
      justify the clinical importance of this search strategy, and accordingly,
      invasive procedures are done less frequently in a higher proportion of younger
      women.

PMID- 16794988
TI  - [Pain management and coping behaviour in premature babies (< 1500 g) at corrected
      age of 36 months influence of neonatal experience and maternal anxiety].
AB  - INTRODUCTION: Neonatal experience of pain and distress can lead to developmental
      problems, which can be associated with long-term emotional and behavioural
      disorders. The aim of the study was to analyse the effects of early experiences
      of pain and maternal reactions on the pain and coping behaviour of preterm
      infants. METHODS: In a prospective longitudinal study of 69 very low birth weight
      (VLBW) preterm infants, neonatal data regarding painful manipulations, analgesics
      and sedatives, and general medical condition (Nursery Neurobiological Risk Score;
      NBRS) were assessed. At the (corrected) age of 36 months, 53 preterm infants and
      a control group of 23 full-term infants were re-examined. Pain and coping
      behaviour were estimated by a questionnaire. Maternal anxiety was assessed in
      semi-structured interviews at the age of 3, 12 and 36 months in the preterm
      group. RESULTS: The mean gestational age was 29 + 0 weeks (23 + 3 to 34 + 1), the
      mean birth weight 1058 g (380 to 1480 g) in preterms and 39 + 3 weeks (37 + 0 to
      42 + 0) and 3379 g (2400 to 4130 g), respectively, for the full-terms. The sex
      ratio was equal, 45.3 % of the preterms were multiples (controls 34.8 %).
      Preterms had higher descriptive scores for all types of pain situations. After
      controlling for other associated factors, a negative correlation between birth
      weight and later pain behaviour in medical situations remained. Preterms had a
      more negative coping behaviour during every day injuries. In terms of coping
      behaviour, only a shorter inpatient treatment in the neonatal period was
      associated with social withdrawal after controlling for other associated factors.
      Maternal anxiety at the age of 12 and 36 months was associated with negative
      coping behaviour following simple injuries. CONCLUSIONS: While preterms do not
      have a higher pain threshold in general, a subgroup does have a higher risk for
      later sensation to pain. Preterms use more unfavourable coping strategies in
      simple injuries which, in turn, seem to be decisively mediated by maternal
      anxiety. Future research should focus on psycho-social factors involved in the
      development of pain reactions, as these can predispose towards behavioural
      disorders.

PMID- 16794989
TI  - Toxicity of indoxacarb and spinosad to the multicolored Asian lady beetle,
      Harmonia axyridis (Coleoptera: Coccinellidae), via three routes of exposure.
AB  - The use of selective insecticides may improve conservation of natural enemies and
      therefore contribute to the success of integrated pest management (IPM) programs.
      In this study, the toxicity of two commonly used selective insecticides,
      indoxacarb and spinosad, to the multicolored Asian lady beetle, Harmonia axyridis
      (Pallas), was evaluated. Third instars and adults of H. axyridis were exposed to
      indoxacarb at 50 and 100% of the field rate (FR), to spinosad at 100% FR and to
      water (untreated check) under laboratory conditions via three routes of exposure.
      Treatments were applied directly on insects (i.e., topical application), on Petri
      dishes (i.e., residues), or on soybean aphids, Aphis glycines Matsumara (i.e.,
      treated prey). Mortality of exposed individuals in each life stage was recorded 2
      and 7 days after treatment. Logistic regression indicated that indoxacarb at 100%
      FR, followed by indoxacarb at 50% FR, was more insecticidal than spinosad to
      third instars. Mortality was higher when H. axyridis were exposed to both
      insecticides via residues followed by treated prey. Indoxacarb at 100 or 50% FR
      was insecticidal to adults. Adults were tolerant to spinosad via all routes of
      exposure. The present results suggest that indoxacarb may decrease H. axyridis
      field populations by causing mortality to larvae and adults via all routes of
      exposure. Implications of the toxicity of indoxacarb to H. axyridis within an IPM
      context and possible reasons for the differences in susceptibility of H. axyridis
      for each route of exposure are discussed.

PMID- 16794990
TI  - Sonic hedgehog is an early developmental marker of intraductal papillary mucinous
      neoplasms: clinical implications of mRNA levels in pancreatic juice.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) are common cystic tumours of the
      pancreas. Sonic hedgehog (SHH) is involved in gastric epithelial differentiation
      and pancreatic carcinogenesis. However, a comprehensive analysis of SHH
      expression in IPMN has not yet been performed. In the present study, one-step
      quantitative real-time reverse transcription-polymerase chain reaction with gene
      specific priming was used to examine mRNA levels in various types of clinical
      samples. SHH expression in IPMN was measured and the possible association of
      gastric epithelial differentiation with development of IPMN was evaluated. In
      bulk tissue analyses (IPMNs, 11 pancreatic cancer, and 20 normal pancreatic
      tissues), IPMN expressed significantly higher levels of SHH than did normal
      pancreas (IPMN versus normal pancreas, p = 0.0025; pancreatic cancer versus
      normal pancreas, p = 0.0132), but SHH expression did not differ between IPMN and
      pancreatic cancer (p = 0.3409). In microdissection analyses (infiltrating ductal
      carcinoma cells from 20 sections, IPMN cells from 20 sections, pancreatitis
      affected epithelial cells from 11 sections, and normal epithelial cells from 12
      sections), IPMN cells expressed significantly higher levels of SHH than did
      cancer cells, normal cells, or pancreatitis-affected ductal cells (all
      comparisons, p < 0.008). Pancreatic juice analyses (20 samples from pancreatic
      cancers, 31 samples from IPMNs, and 27 samples from chronic pancreatitis)
      revealed that SHH expression differed significantly between IPMN juice and
      pancreatitis juice (p < 0.0001), and between cancer juice and pancreatitis juice
      (p = 0.0125). Receiver operating characteristic curve analyses revealed that SHH
      measurement in pancreatic juice was useful for discriminating IPMN from chronic
      pancreatitis (area under the curve = 0.915; 95% confidence interval: 0.796
      0.976). The data suggest that overexpression of SHH is an early event in the
      development of IPMN and that SHH measurement in pancreatic juice may provide some
      advantages for the treatment or follow-up of a subset of patients with IPMN or
      chronic pancreatitis.

PMID- 16794991
TI  - A score test for overdispersion in zero-inflated poisson mixed regression model.
AB  - Count data with extra zeros are common in many medical applications. The zero
      inflated Poisson (ZIP) regression model is useful to analyse such data. For
      hierarchical or correlated count data where the observations are either clustered
      or represent repeated outcomes from individual subjects, a class of ZIP mixed
      regression models may be appropriate. However, the ZIP parameter estimates can be
      severely biased if the non-zero counts are overdispersed in relation to the
      Poisson distribution. In this paper, a score test is proposed for testing the ZIP
      mixed regression model against the zero-inflated negative binomial alternative.
      Sampling distribution and power of the test statistic are evaluated by simulation
      studies. The results show that the test statistic performs satisfactorily under a
      wide range of conditions. The test procedure is applied to pancreas disorder
      length of stay that comprised mainly same-day separations and simultaneous
      prolonged hospitalizations.

PMID- 16794992
TI  - The consumer welfare implications of the hospital ownership mix in the US: an
      exploratory study.
AB  - This paper offers an empirical test concerning how hospital ownership mix affects
      consumer welfare in the US. The test compares the market benefits and costs
      resulting from an increased presence of nonprofit hospitals by observing
      empirically how the nonprofit market share impacts hospital care utilization at
      the margin. The empirical results suggest that too many not-for-profit and public
      hospitals exist in the inpatient care segment of the typical hospital services
      industry of the US. In contrast, the empirical findings indicate that too many
      for-profit hospitals operate in the outpatient care portion of the hospital
      services industry. The policy implication is that more quality of care per dollar
      might be obtained by promoting increased for-profit activity to inpatient care
      and more nonprofit activity to outpatient care in some market areas. This
      conclusion, however, is tempered with several caveats. We discuss these and also
      make recommendations for further research.

PMID- 16794994
TI  - Changes in pattern of use, clinical characteristics and persistence rate of
      hormone replacement therapy among postmenopausal women after the WHI publication.
AB  - The WHI was stopped prematurely because of an increased risk of breast cancer,
      stroke and cardiovascular diseases (CVD) in the hormone replacement therapy (HRT)
      arm of the trial. Changes in the use of HRT are expected. OBJECTIVE: To assess
      the impact of the Women's Health Initiative (WHI) publication on the rate of HRT
      prescription, and the clinical characteristics and persistence rate of new users
      and its determinants. METHODS: From the RAMQ databases, the total numbers of HRT
      prescriptions, and of new HRT's users were calculated between 2 January 1998 and
      31 May 2003. To assess the clinical characteristics of women, two retrospective
      cohorts of new HRT's users were constructed before (pre-WHI) and after (post-WHI)
      the WHI study publication. The persistence rate after 1 year of follow-up was
      estimated using a Kaplan-Meier analysis. Cox regression models were used to
      estimate the rate ratio of HRT cessation. RESULTS: The total numbers of HRT users
      and of new users declined respectively by 28% and 50% in post-WHI. The standard
      dosage of HRT was significantly less used, while the proportion of women with
      risk factors of CVD or at very high risk of coronary artery disease (CAD) did not
      change. The rate of persistence in the pre-WHI cohort was 59% compared to 45% in
      the post-WHI (p < 0.0001), and women with risk factors of CVD or at very high
      risk of CAD were less likely to cease their HRT. CONCLUSION: One year after
      publication, significant changes had already occurred in the trends of use,
      women's characteristics and estrogen dosage. No change in the proportion of new
      users with CVD risk factors or at very high risk of CAD was seen.

PMID- 16794993
TI  - Vaccines, antibiotics, and atopy.
AB  - PURPOSE: Early exposure to vaccines and antibiotics may increase the risk of
      developing atopy by protecting against infectious agents and reducing duration
      and severity of infections (the hygiene hypothesis). It may also shift the
      developing immune system towards a more allergic response. We assess possible
      associations in young allergy clinic patients. METHODS: We conducted a case
      control study of 6- to 16-year-old new allergy clinic patients who were skin
      tested for inhalant allergens during 1987-2001 and enrolled in KPNW since birth
      (n = 1074). Atopic cases had positive tests for at least one inhalant allergen.
      Non-atopic controls had negative tests for all inhalant allergens. Using logistic
      regression analysis, we estimated atopy odds ratios for vaccine and antibiotic
      exposure variables and associations between vaccine and antibiotic exposures
      during the first 2 years of life and subsequent new allergy diagnoses. RESULTS:
      Atopy was not significantly associated with numbers of vaccine and antigen doses,
      or number of different antigens during the first 2 years of life. Number of
      antibiotic prescriptions was negatively associated with atopy risk. Neither
      exposure was significantly associated with risk of new allergy diagnoses in
      atopic children. CONCLUSIONS: Atopy development appears to be unrelated to early
      vaccine exposure. Frequency of antibiotic prescriptions during early life, a
      proxy for infection frequency, appears to protect against allergic sensitization.
      Neither vaccines nor antibiotics appear to induce subsequent allergic reactions
      in atopic children.

PMID- 16794995
TI  - A mouse carrying the green fluorescent protein gene targeted to the Pdx1 locus
      facilitates the study of pancreas development and function.
AB  - The pancreatic and duodenal homeobox gene 1 (Pdx1) has multiple roles in the
      specification and development of foregut endoderm-derived tissues. We report the
      characterization of a mouse line in which the gene encoding green fluorescent
      protein (GFP) has been targeted to the Pdx1 locus, allowing the visualization of
      Pdx1 expressing cells. Analysis of GFP expression during development showed that
      the reporter faithfully reproduced the known expression pattern of Pdx1. We
      demonstrate the utility of this mouse line for the isolation of Pdx1(+) cells by
      fluorescence-activated cell sorting and for the real-time observation of Pdx1(+)
      cells in an ex vivo embryonic pancreas culture system. This mouse model should
      prove useful for the study of pancreas development and regeneration.

PMID- 16794996
TI  - Combining functional and topological properties to identify core modules in
      protein interaction networks.
AB  - Advances in large-scale technologies in proteomics, such as yeast two-hybrid
      screening and mass spectrometry, have made it possible to generate large Protein
      Interaction Networks (PINs). Recent methods for identifying dense sub-graphs in
      such networks have been based solely on graph theoretic properties. Therefore,
      there is a need for an approach that will allow us to combine domain-specific
      knowledge with topological properties to generate functionally relevant sub
      graphs from large networks. This article describes two alternative network
      measures for analysis of PINs, which combine functional information with
      topological properties of the networks. These measures, called weighted
      clustering coefficient and weighted average nearest-neighbors degree, use weights
      representing the strengths of interactions between the proteins, calculated
      according to their semantic similarity, which is based on the Gene Ontology terms
      of the proteins. We perform a global analysis of the yeast PIN by systematically
      comparing the weighted measures with their topological counterparts. To show the
      usefulness of the weighted measures, we develop an algorithm for identification
      of functional modules, called SWEMODE (Semantic WEights for MODule Elucidation),
      that identifies dense sub-graphs containing functionally similar proteins. The
      proposed method is based on the ranking of nodes, i.e., proteins, according to
      their weighted neighborhood cohesiveness. The highest ranked nodes are considered
      as seeds for candidate modules. The algorithm then iterates through the
      neighborhood of each seed protein, to identify densely connected proteins with
      high functional similarity, according to the chosen parameters. Using a yeast two
      hybrid data set of experimentally determined protein-protein interactions, we
      demonstrate that SWEMODE is able to identify dense clusters containing proteins
      that are functionally similar. Many of the identified modules correspond to known
      complexes or subunits of these complexes.

PMID- 16794997
TI  - A novel soft and cotton-like chitosan-sugar nanoscaffold.
AB  - A novel type of chitosan nanoscaffold with a soft and cotton-like appearance is
      proposed. The key to success is based on two points: (i) the change in morphology
      of chitin whisker to chitosan nanoscaffold and (ii) the surface modification of
      the nanoscaffold chitosan with a sugar unit. Simple deacetylation of chitin
      whisker gives a colloidal solution of chitosan, of which the chitosan is in a
      nanoscaled scaffold. Surface functionalization of the chitosan nanoscaffold with
      lactose or maltose via a heterogeneous system in water at room temperature
      results in a soft and cotton-like chitosan containing mesopores. As all steps are
      organic solvent free, this chitosan-sugar nanoscaffold might be a promising
      material for biopolymer-supported tissue engineering.

PMID- 16794998
TI  - Spectrum and presentation of pediatric malignancies in the HIV era: experience
      from Blantyre, Malawi, 1998-2003.
AB  - BACKGROUND: Data on childhood cancers in Africa are sparse, particularly since
      the spread of HIV. We aimed to document the frequency of pediatric cancers
      presenting to a large central hospital in Malawi, detailing the presenting
      features, initial investigations, and HIV status of these children. PROCEDURE: A
      retrospective audit of the spectrum and clinical presentation of cancers among
      children (<16 years) seen at Queen Elizabeth's Central Hospital (QECH), between
      1998 and 2003. RESULTS: Seven hundred seven children with cancer were seen, the
      number of cases per year increased over the time period; 50% (351) had Burkitt
      lymphoma, 13% (89) had retinoblastoma, and 9% (61) had Kaposi sarcoma, with a
      variety of other tumors comprising the remainder. Kaposi sarcoma markedly
      increased in frequency over time. Histological verification of diagnosis was
      available for 49% (348). The proportion of children with cancer who were tested
      for HIV increased over time, but varied by cancer type. Amongst those tested, the
      seroprevalence was 93% (52/56) for children with Kaposi sarcoma, 4% (11/289) for
      those with Burkitt lymphoma, 31% (8/26) for those with other non-Hodgkin
      lymphomas, 7% (1/15) for those with Hodgkin disease, and 5% (5/103) for those
      with other cancers. CONCLUSIONS: The number of cases seen per year has increased
      over the study period for almost all cancers, but in particular for Kaposi
      sarcoma. Burkitt lymphoma remains the commonest pediatric tumor in Malawi. In the
      case of Burkitt lymphoma, non-Hodgkin lymphoma, and Kaposi sarcoma there is a
      significant difference in the presentation of HIV-seropositive and -seronegative
      children.

PMID- 16794999
TI  - Renin-induced hypertension in Wilms tumor patients.
AB  - BACKGROUND: Since the report that hypertension associated with Wilms tumor (WT)
      may be renin-induced, no larger series than 13 patients have been published.
      Nevertheless, angiotensin converting enzyme (ACE) inhibitors have become
      treatment of choice for hypertension in WT patients. The purpose of this study
      was to investigate the correlation between plasma renin levels and blood pressure
      in a larger cohort of WT patients. PROCEDURE: In this retrospective, single
      center study, data on blood pressure and plasma renin were analyzed in 86 WT
      patients treated according to the consecutive SIOP protocols 6, 9, 93-01, and
      2001. RESULTS: At diagnosis, 47 WT patients suffered from hypertension (55%). In
      31 of these patients plasma renin levels were analyzed; increased plasma renin
      levels were found in 25/31 patients (81%). In contrast, normal plasma renin
      levels were measured in 8/13 of the patients with a normal blood pressure (P =
      0.012). Twenty-eight children received antihypertensive treatment before surgery,
      in 25 of them blood pressure normalized before surgery. Blood pressure was normal
      directly after surgery in all patients but 4, in whom blood pressure recovered to
      normal within a few weeks. CONCLUSIONS: This retrospective study shows that
      hypertension in WT patients is associated with elevated plasma renin levels,
      indicating that ACE inhibitors may be a good therapeutic option in at least a
      subset of WT patients with hypertension before nephrectomy.

PMID- 16795002
TI  - Prediction of human drug clearance from animal data: application of the rule of
      exponents and 'fu Corrected Intercept Method' (FCIM).
AB  - The objective of this study is to evaluate the predictive performance of the rule
      of exponents (ROE) and 'fu Corrected Intercept Method' (FCIM) for the human drug
      clearance. Different classes of drugs such as extensively metabolized, renally
      excreted, renally secreted, and biliary excreted drugs were used in this
      analysis. The results of the study indicated that both these methods under given
      conditions are extremely useful for the prediction of human drug clearance. There
      are certain situations under which one of these methods is more suited than the
      other method. Overall, it appears that a rational use of FCIM and the ROE can
      help a great deal in obtaining a better estimate of the human drug clearance for
      a wide variety of drugs. The advantages and disadvantages of these two methods
      are also discussed.

PMID- 16795003
TI  - Stealth PEG-PHDCA niosomes: effects of chain length of PEG and particle size on
      niosomes surface properties, in vitro drug release, phagocytic uptake, in vivo
      pharmacokinetics and antitumor activity.
AB  - A series of novel niosomes with the amphiphilic copolymer of poly (methoxy
      polyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) acted
      as surface modification materials were prepared and Hydroxycamptothecin (HCPT)
      was used as a model drug. This work concentrated on the effects of PEG chain
      length and particle sizes on the niosomes surface properties, in vitro drug
      release, phagocytic uptake, in vivo pharmacokinetics and antitumor activity.
      Within the range of PEG Mw from 2000 to 10000, the increasing zeta potential
      (from -16.08 to -5.25 mv) and thicker fixed aqueous layer (3.82 to 5.78 nm) would
      facilitate the niosomes' stealth effects, while the reduced PEG chain density
      (from 0.53 to 0.17 PEG/nm2) and the quickened speed of drug release would
      diminish the effects. As a result, the PEG5000-PHDCA niosomes had the least
      phagocytic uptake, the longest half-life of 11.46 h and the best tumor inhibition
      rate of 97.1%. In the groups different in particle size (PEG5000-PHDCA niosomes
      from 92.5 to 204.6 nm), the bigger particles could be uptaken by macrophages more
      quickly, regardless of the changes of other physicochemical parameters.
      Correspondingly, PEG5000-PHDCA niosomes with particle sizes of 92.5, 144.2, 204.6
      nm could extend the half-life of HCPT to 11.46, 6.33, 4.46 h, respectively. At
      last, the tumor inhibition rate of PEG5000-PHDCA niosomes (92.5 nm) at a dose of
      2 mg/kg was five times that of HCPT injection at 4 mg/kg. The stealth effects of
      the PEG-PHDCA niosomes and the enhanced stability of lactone form of HCPT were
      accountable for the powerful antitumor effects of niosomes.

PMID- 16795004
TI  - Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients.
AB  - Lewy bodies, the pathological hallmark of Parkinson's disease (PD), consist
      largely of alpha-synuclein, a 14.5-kDa presynaptic neuronal protein implicated in
      familial PD. An increased copy number and elevated expression of wild-type alpha
      synuclein (SNCA) has been shown to cause early-onset familial PD. However, it is
      not clear whether increased alpha-synuclein expression also plays a role in the
      pathogenesis of sporadic disease. In the current study, we analyzed the levels of
      SNCA-mRNA in affected brains of sporadic PD patients. We compared the levels of
      steady state SNCA-mRNA in 7 sporadic PD brain samples and 7 normal controls using
      real-time polymerase chain reaction of RNA extracted from mid-brain tissue,
      including the substantia nigra. Despite that there is neuronal loss in the
      substantia nigra of PD brains, overall the SNCA-mRNA levels were increased in PD
      brains an average of nearly fourfold over normal control mid-brain, although
      there was much greater variability in samples from PD patients compared to
      controls. Frontal cortex samples from selected individuals were also analyzed.
      SNCA-mRNA levels were not significantly changed in PD frontal cortex compared to
      controls. These results suggest that elevated expression levels of SNCA-mRNA are
      found in the affected regions of PD brain and support the hypothesis that
      increases in alpha-synuclein expression is associated, among other factors, with
      the development of sporadic PD.

PMID- 16795005
TI  - 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine, a nucleoside reverse transcriptase
      inhibitor, is highly potent against all human immunodeficiency viruses type 1 and
      has low toxicity.
AB  - An idea to use 4'-C-substituted-2'-deoxynucleoside derivatives was proposed based
      on a working hypothesis to solve the problems of existing acquired immune
      deficiency syndrome chemotherapy (highly active antiretroviral therapy).
      Subsequent studies have successfully proved the validity of the idea and resulted
      in the development of 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine, a nucleoside
      reverse transcriptase inhibitor, which is highly potent to all human
      immunodeficiency viruses type 1 (HIV-1s) including multidrug-resistant HIV-1 and
      has a low toxicity.

PMID- 16795006
TI  - Oxime palladacycles revisited: stone-stable complexes nonetheless very active
      catalysts.
AB  - Our review critically presents the main achievements, advantages, and limitations
      of oxime palladacycles as high-turnover catalysts for Heck, as well as homo- and
      cross-coupling reactions such as Suzuki-Miyaura, Stille, Ullmann-type, Cassar
      Heck-Sonogashira, sila-Sonogashira, Glaser-type, Hiyama, and alkoxycarbonylation
      reactions. New developments in this area are reviewed from a mechanistic and
      synthetic point of view. The role of oxime palladacycles as a source of highly
      active zero-valent palladium species is also discussed.

PMID- 16795007
TI  - Catalysts for new tasks: preparation and applications of tunable ruthenium
      catalysts for olefin metathesis.
AB  - A continuous survey across structures, made over the past decades, has led to the
      development of highly active olefin metathesis catalysts for sophisticated
      synthetic tasks and for polymer technology. In this paper, our efforts toward
      novel and improved ruthenium complexes with even better performance in olefin
      metathesis are described. Oxygen ether derivatives 3, pioneered by Hoveyda,
      exhibit high activity and possess excellent functional group tolerance. We have
      successfully fine-tuned catalyst 3b to increase its activity and applicability by
      the introduction of electron-withdrawing groups to diminish the donor properties
      of the oxygen atom. As a result, the stable and easily accessible nitro
      substituted catalyst 6 has found a number of successful applications in various
      research and industrial laboratories. We were intrigued by the possibility to
      further fine-tune the Hoveyda-type catalysts by combining two activating effects
      steric and electronic-in a single catalyst. This was possible to achieve in so
      called scorpio carbenes, which are currently under investigation in our
      laboratory. These modifications can be used not only to control the catalyst
      activity, but also to alter its physical-chemical properties, such as solubility
      in a given medium or an affinity to silica gel. An example of immobilization
      strategy based on this concept is presented.

PMID- 16795008
TI  - Silsesquioxane-based nanocomposite dendrimers with photo-luminescent and charge
      transport properties.
AB  - The synthesis and characterization of octavinylsilsesquioxane (OVS)-based
      nanocomposite dendrimers with luminescent and charge transport properties are
      reported. The nanocomposite dendrimers were prepared in high yield using mild
      Heck chemistry of mono-haloaromatic compounds with the peripheral vinylsilane
      groups of OVS. Attachment of 2-naphthalene, 2-(9,9-dimethyl)fluorene, and 2-(4
      phenyl)-5-(1-naphthyl)-1,3,4-oxadiazole resulted in materials with blue-violet
      emission (360-380 nm) and photo-luminescent quantum efficiencies (PLQEs) from 1
      to 26%. Blue-green emission was observed for attachment of 1-pyrene, 9
      anthracene, and N1-(4-phenyl)-N1,N4,N4-triphenylbenzene-1,4-diamine with PLQEs
      ranging from 23 to 50%. Despite the planar characteristics of the organic
      dendrons, the nanocomposite dendrimers are completely amorphous and have high
      glass transition temperatures (Tg) ranging from 115 to 186 degrees C with
      decomposition temperatures (Td) exceeding 450 degrees C. Matrix-assisted laser
      desorption ionization-time of flight shows that unlike traditional Heck
      chemistry, haloaromatic compounds are adding twice across the vinylsilane groups.
      Finally, organic light emitting diodes using the aromatic amine-based dendrimer
      as hole injection layers show 55% improvement in device efficiency over
      traditional materials (5.16 vs. 3.24 cd A(-1)) with brightness levels exceeding
      40,000 cd m(-2).

PMID- 16795009
TI  - Understanding processing-induced phase transformations in erythromycin-PEG 6000
      solid dispersions.
AB  - Since the quality and performance of a pharmaceutical solid formulation depend on
      solid state of the drug and excipients, a thorough investigation of potential
      processing-induced transformations (PITs) of the ingredients is required. In this
      study, the physical phenomena taking place during formulation of erythromycin
      (EM) dihydrate solid dispersions with polyethylene glycol (PEG) 6000 by melting
      were investigated. PITs were monitored in situ using variable temperature X-ray
      powder diffraction (VT-XRPD), differential scanning calorimetry (DSC), and hot
      stage microscopy (HSM). Possible intermolecular interactions between the drug and
      polymer in the solid state were further studied by Fourier transform infrared
      (FTIR) spectroscopy. While in the absence of PEG the dehydration was the only
      transformation observed, hot-melt processing with the polymer caused the drug to
      undergo multiple phase transformations (EM dihydrate --> EM dehydrate --> EM
      anhydrate). This alteration in phase behavior of EM was attributed to the ability
      of PEG in promoting nucleation and crystal growth of the EM anhydrate through a
      solvent-mediated route. In situ monitoring of solid dispersion formation,
      especially by VT-XRPD and HSM, enabled both early-stage detection of phase
      transformations during the hot-melt processing and better process understanding.

PMID- 16795010
TI  - Determination of drug plasma protein binding by solid phase microextraction.
AB  - The plasma protein binding of drugs has been shown to have significant effects on
      the quantitative relationship between clinical pharmacokinetics and
      pharmacodynamics. In many clinical situations, measurement of the total drug
      concentration does not provide the needed information concerning the unbound
      fraction of drug in plasma, which is available for pharmacodynamic action.
      Therefore, the accurate determination of unbound plasma drug concentrations is
      important in understanding drug action. Many methodologies exist for determining
      the extent of plasma protein binding, but different methods produce a rather wide
      range of results for the same compound at the same concentration level. The solid
      phase microextraction (SPME) method reported in the present study attempts to
      eliminate many experimental variables that could lead to the lack of
      reproducibility, such as the variable content of organic solvent or ionic
      strength in plasma, pH shifts, and volume shifts. Five well-known drugs were
      chosen to study plasma protein binding: ibuprofen, warfarin, verapamil,
      propranolol, and caffeine, with high, intermediate and low binding properties.
      Dilution of plasma with isotonic PBS or incubation with 10% CO(2) in the
      atmosphere was found to compensate for changes in pH during incubation. The data
      obtained using these pH-controlled methods correlate well with the average values
      of plasma protein binding found in the literature. SPME, which uses an extraction
      phase that dissolves or adsorbs the drug of interest and rejects proteins,
      overcomes several limitations of currently available techniques and is a
      thermodynamically sound method, since the measurements are always performed at
      equilibrium. Compared to other methods, SPME offers several advantages: small
      sample size, short analysis time, possibility to automate, and ability to
      directly study complex samples.

PMID- 16795011
TI  - Static light scattering and small-angle neutron scattering study on aggregated
      recombinant gelatin in aqueous solution.
AB  - Recombinant gelatins are currently evaluated as new excipients for pharmaceutical
      formulations. They can differ from nonrecombinant gelatins because of intentional
      alteration of the amino acid sequence and specific properties of the expression
      systems used. This may affect their solution behavior. In the present work,
      aqueous solutions of a histidine-containing recombinant gelatin (RG-15-His) were
      analyzed. Dynamic light scattering (DLS) and loss of absorbance at 200 nm upon
      centrifugation indicated the formation of aggregates within 1 day upon sample
      preparation. Static light scattering (SLS) and small-angle neutron scattering
      (SANS) experiments showed that the aggregate's size was > or =300 nm, and that
      aggregates are composed of thin, rigid rods of 37 +/- 5 nm in length. The
      observed aggregation was not detectable by circular dichroism (CD), Fourier
      transform infrared spectroscopy (FTIR), and cryo transmission electron microscopy
      (cryo-TEM). SANS experiments, which are not frequently used in the pharmaceutical
      field, provided additional morphological information about the recombinant
      gelatin in solution. The results show that combining SLS and SANS is a broadly
      applicable, complementary approach for detecting aggregation of proteins and
      other biomolecules and for obtaining structural information about the aggregates.

PMID- 16795012
TI  - Formulation and evaluation of a testosterone transdermal spray.
AB  - The long-term goal is to develop a spray formulation for transdermal testosterone
      delivery, and to optimize the drug's skin permeability. Testosterone transport
      from a series of ethanol/propylene glycol (PG)/water formulations was assessed in
      vitro across hairless rat skin, and the optimal composition determined. The
      formulation was then modified for delivery from a mechanical spray, and from an
      aerosol containing a high percentage of propellant. Drug transport was greatest
      from a saturated solution in 1:1:1 ethanol/PG/water (1.7 +/- 0.2 microg/cm(2) .
      h); five spray formulations were then tested, but only 1:1 ethanol/PG achieved a
      comparable flux. Increasing the % ethanol in the mixture increased evaporation
      rate but did not alter testosterone delivery. Formulation as an aerosol produced
      primarily unstable vehicles (phase separation, crystallization). Only 3:1
      ethanol/PG remained stable, but no significant improvement in drug transport was
      observed (testosterone precipitated rapidly at the skin surface). The 1:1:1
      ethanol/PG/water saturated solution suggested that some penetration enhancement
      was possible. Eliminating water to improve sprayability identified 1:1 ethanol/PG
      as a vehicle, which might allow transient supersaturation (and improved
      delivery). However, this effect was not improved by using a pressurized aerosol
      due to instability. Finally, testosterone fluxes were 5 to 10-fold lower than
      those required for useful transdermal therapy.

PMID- 16795013
TI  - A global examination of allometric scaling for predicting human drug clearance
      and the prediction of large vertical allometry.
AB  - Allometrically scaled data sets (138 compounds) used for predicting human
      clearance were obtained from the literature. Our analyses of these data have led
      to four observations. (1) The current data do not provide strong evidence that
      systemic clearance (CL(s); n = 102) is more predictable than apparent oral
      clearance (CL(po); n = 24), but caution needs to be applied because of potential
      CL(po) prediction error caused by differences in bioavailability across species.
      (2) CL(s) of proteins (n = 10) can be more accurately predicted than that of non
      protein chemicals (n = 102). (3) CL(s) is more predictable for compounds
      eliminated by renal or biliary excretion (n = 33) than by metabolism (n = 57).
      (4) CL(s) predictability for hepatically eliminated compounds followed the order:
      high CL (n = 11) > intermediate CL (n = 17) > low CL (n = 29). All examples of
      large vertical allometry (% error of prediction greater than 1000%) occurred only
      when predicting human CL(s) of drugs having very low CL(s). A qualitative
      analysis revealed the application of two potential rules for predicting the
      occurrence of large vertical allometry: (1) ratio of unbound fraction of drug in
      plasma (f(u)) between rats and humans greater than 5; (2) C logP greater than 2.
      Metabolic elimination could also serve as an additional indicator for expecting
      large vertical allometry.

PMID- 16795014
TI  - Thiol exchange: an in vitro assay that predicts the efficacy of novel
      homocysteine lowering therapies.
AB  - Elevated plasma total homocysteine (tHcy) is a risk factor for atherosclerosis.
      Hcy is 70-80% bound to albumin as a disulfide. Recent trials have evaluated
      ability of thiol-containing drugs to exchange with protein bound Hcy and
      consequently increase its renal clearance. The objective of this study was to
      develop an in vitro assay to predict the efficacy of thiol-containing drugs to
      lower tHcy in the clinical setting. The assay was used to test the effects of N
      acetylcysteine (NAC), mesna, captopril, dimercaptosuccinic acid (DMSA), and
      penicillamine. Hcy was added in vitro to plasma of healthy subjects (n = 6) and
      equilibrated. Concentrations of thiol exchange agent were added and incubated at
      37 degrees C. Aliquots were removed at selected intervals and free Hcy
      determined. Mesna, captopril, and NAC caused a concentration-dependent increase
      in free Hcy. Three-hundred micromolar mesna and captopril had a greater effect
      than equimolar NAC, increasing free Hcy by 33.9 +/- 5.0% and 32.0 +/- 2.6%,
      respectively compared to 22.3 +/- 2.4% for NAC, p < 0.001. Our in vitro results
      indicate that mesna, captopril, and NAC effectively exchange with covalently
      bound Hcy. This assay can act as screening tool for novel tHcy lowering therapies
      and should spare the expense of negative trials.

PMID- 16795015
TI  - Sertaconazole/hydroxypropyl-beta-cyclodextrin complexation: isothermal titration
      calorimetry and solubility approaches.
AB  - Complexation of sertaconazole (SN) with hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) was characterized by phase-solubility diagram measurements and isothermal
      calorimetry (ITC) in aqueous medium, and by differential scanning calorimetry
      (DSC), Raman spectroscopy and X-ray diffractometry in solid state. The strongest
      interaction was observed at pH 1.2, at which two different 1:1 complexes can be
      formed depending on the hydrophobic ring of the drug involved in the process. At
      pH 5.8 and 7.4 the likelihood of 1:2 stoichiometry increases as a consequence of
      the simultaneous complexation of the nonprotonized imidazolyl and the
      dichlorophenyl groups. In the presence of 20% HP-beta-CD, SN solubility is
      enhanced by a factor of 116, 107, and 5 at pH 1.2, 5.8, and 7.4, respectively.
      Complexation enthalpy recorded by ITC showed the same tendency which confirms the
      practical interest of this technique for fast screening of the potential of CDs
      as drug solubilizers. Solubility and dissolution rate of the drug from compacts
      prepared with freeze-dried complexes were significantly greater than those
      obtained with SN powder or compacts made with physical blends.

PMID- 16795016
TI  - Hyperthermia-induced antitumor activity of thermosensitive polymer modified
      temperature-sensitive liposomes.
AB  - Temperature-sensitive liposomes (TS-liposomes) have been studied for
      chemotherapeutic purposes to enhance the release of anticancer drugs at tumor
      sites. In this study, we prepared poly(N-isopropylacrylamide-co-acrylamide)
      (PNIPAM-AAM) and polyethylene glycol (PEG)-modified TS-liposomes (PETS
      liposomes). PETS-liposomes significantly increased in vitro drug release in serum
      compared with PEG-fixed or PNIPAM-AAM-modified liposomes. Furthermore,
      incorporation of both PNIPAM-AAM and PEG into PETS-liposomes enhanced the
      stabilities of liposomes in serum by inhibiting protein adsorption. In addition,
      to investigate the therapeutic efficacy of doxorubicin (DOX)-loaded PETS
      liposomes, the in vivo antitumor activity of liposomes in combination with
      hyperthermia was evaluated in a B16F10 melanoma tumor-bearing mouse model. PETS
      liposomes showed much higher levels of tumor growth inhibition than PEG-fixed or
      PNIPAM-AAM-modified TS-liposomes. Moreover, the antitumor activity of PETS
      liposomes was enhanced significantly when they were administered in combination
      with hyperthermia. PETS-liposomes were found to be highly efficacious carriers
      for the in vivo delivery of anticancer drugs, and to have potential anticancer
      applications in combination with hyperthermia.

PMID- 16795017
TI  - Labetalol absorption kinetics: rat small intestine and colon studies.
AB  - Labetalol is a widely used drug for the management of hypertension, which is
      preferably administered by the oral route despite its low bioavailability. The
      objective of this study is to ascertain the mechanisms underlying its absorption
      as an approach to help in predicting the influence of dosage changes, possible
      drug-drug and drug-fruit juice interactions. Perfusion experiments have been
      performed in rats in two sites of absorption: the intestine and the colon. The
      nonlinearity of the process has been established by means of the assay of a wide
      range of concentrations (2-2000 microM). Fitting of the concentration versus time
      data allows the estimation of passive diffusion constant in the intestine (1.42
      +/- 0.05/h) and the colon (1.13 +/- 0.06/h), V(m) and K(m) of the input process
      (9.85 +/- 4.98 microM/h, and 10.44 +/- 26.16 microM, respectively) and K(m) of an
      efflux system (0.53 +/- 1.16 microM) and V(m) in both intestinal segments (2.60
      +/- 11.37 microM . /h in the intestine and 0.66 +/- 1.38 microM . /h in the
      colon). The efflux carrier implicated is identified by means of several
      inhibition experiments, whose inhibition ability is mathematically estimated.
      Results suggest the p-glycoprotein as responsible for the efflux of labetalol.

PMID- 16795018
TI  - The use of colloid probe microscopy to predict aerosolization performance in dry
      powder inhalers: AFM and in vitro correlation.
AB  - The atomic force microscope (AFM) colloid probe technique was utilized to measure
      cohesion forces (separation energy) between three drug systems as a function of
      relative humidity (RH). The subsequent data was correlated with in vitro
      aerosolization data collected over the same RH range. Three drug-only systems
      were chosen for study; salbutamol sulphate (SS), triamcinolone acetonide (TAA),
      and di-sodium cromoglycate (DSCG). Analysis of the AFM and in vitro data
      suggested good correlations, with the separation energy being related inversely
      to the aerosolization performance (measured as fine particle fraction, FPF(LD)).
      In addition, the relationship between, cohesion, RH, and aerosolization
      performance was drug specific. For example, an increase in RH between 15% and 75%
      resulted in increased cohesion and decreased FPF(LD) for SS and DSCG. In
      comparison, for TAA, a decrease in cohesion and increased FPF(LD) was observed
      when RH was increased (15-75%). Linear regression analysis comparing AFM with in
      vitro data indicated R(2) values > 0.80, for all data sets, suggesting the AFM
      could be used to indicate in vitro aerosolization performance.

PMID- 16795019
TI  - Enhanced bioavailability of a new thiazolidine derivative FPFS-410, an
      antidiabetic and lipid-lowering drug, after oral administration of its
      hydroxypropyl-beta-cyclodextrin complex to bile duct-cannulated rats.
AB  - The effect of bile acids on bioavailability of FPFS-410 (2-(N-Cyanoimino)-5-{(E)
      4-styrylbenzylidene}-4-oxothiazolidine) after oral administration of the drug and
      its 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) complex was investigated. The
      complexation with HP-beta-CyD increased the oral bioavailability of FPFS-410 in
      normal rats in a HP-beta-CyD concentration-dependent manner, compared with that
      of drug alone. In bile duct-cannulated rats, bile acid concentrations in pylic
      serum and biliary were decreased to 18% and 14% of sham-operated rats,
      respectively. After oral administration of the HP-beta-CyD complex, the plasma
      levels of FPFS-410 were lower in bile duct-cannulated rats than in sham-operated
      rats up to 1 h, however, this order reversed from 2 to 12 h. The plasma levels of
      M1, a dominant metabolite of FPFS-410 in rats, significantly decreased until 2 h
      after administration of the complex in bile duct-cannulated rats, compared with
      in sham-operated rats. Bioconversion of FPFS-410 to M1 and CYP3A2 expression in
      the liver was markedly lowered by bile duct-cannulation. Bile duct-cannulation
      did not, however, affect the serum levels of estradiol. These results suggest
      that bile acids have a pivotal role for bioavailability of FPFS-410 after oral
      administration of the FPFS-410 complex with HP-beta-CyD through CYP3A2 activity
      in liver of rats.

PMID- 16795021
TI  - Aluminum hydroxide adjuvant produced under constant reactant concentration.
AB  - Aluminum hydroxide adjuvant, AlO(OH), is used to potentiate the immune response
      to vaccines by adsorbing the antigen. The structure of aluminum hydroxide
      adjuvant is unusual as it is crystalline but has a high surface area due to its
      very small primary particles. The purpose of this study was to investigate the
      chemical and thermal conditions required to synthesize aluminum hydroxide
      adjuvant that is stable and exhibits a high protein adsorptive capacity. Aluminum
      hydroxide adjuvant was precipitated using a procedure in which the concentration
      of reactants was maintained constant throughout the precipitation. The
      precipitation variables were: 2.50, 2.75, and 3.00 OH/Al molar ratio; 0.5, 4.0,
      and 5.0 M NaCl; and 25, 60, and 65 degrees C. High sodium chloride concentration
      and high temperature facilitated the formation of AlO(OH) rather than crystalline
      forms of aluminum hydroxide, Al(OH)(3). The AlO(OH) produced was not stable
      because crystalline forms of aluminum hydroxide formed during aging at room
      temperature. Aluminum hydroxide adjuvant was stabilized for the study period of
      12 weeks at room temperature by either the addition of 3.0 M NaCl after
      precipitation and washing or hydrothermal treatment at 110 degrees C for 4 h.
      Stabilization by the addition of sodium chloride required a hypertonic
      concentration of sodium chloride and was not practical as vaccines for parenteral
      administration are desired to be isotonic (equivalent to 0.15 M NaCl).
      Stabilization by hydrothermal treatment produced aluminum hydroxide adjuvant,
      which exhibited a high protein adsorptive capacity that did not change during the
      12-week study period.

PMID- 16795020
TI  - Polymeric systems for amorphous Delta 9-tetrahydrocannabinol produced by a hot
      melt method. Part I: chemical and thermal stability during processing.
AB  - The objective of the present research was to investigate the stability of an
      amorphous drug, Delta(9)-tetrahydrocannabinol (THC) in polymer-based transmucosal
      systems. THC was incorporated in polyethylene oxide and hydroxypropylcellulose
      matrices by a hot-melt fabrication procedure, utilizing various processing aids.
      The chemical stability of the drug in the polymeric matrices was investigated
      with respect to processing temperature, processing time, formulation additives,
      and storage conditions. HPLC analysis of the THC-loaded systems indicated that
      the extent of drug degradation was influenced by all of the above mentioned
      variables. THC was particularly unstable in the vitamin E succinate-processed
      films, indicating a potential incompatibility. Thermal stability of the drug,
      polymers, and other ingredients at the elevated processing temperatures during
      the fabrication procedure, was evaluated using the isothermal mode of thermo
      gravimetric analysis. When held at 160 and 200 degrees C, the weight percentage
      of THC decreased linearly as a function of time. Weight loss was controlled by
      blending the drug with polymers, PEO and HPC, of which PEO was determined to be
      more effective. Although higher temperatures lowered the polymer melt viscosity,
      THC and other materials were chemically and thermally unstable at such high
      temperatures. Due to this, matrix fabrication was found to be favorable at
      relatively lower temperatures, such as 120 degrees C.

PMID- 16795022
TI  - Contribution of lysosomes to concentrative uptake of DX-9065a into rat liver.
AB  - This study evaluates the distribution profile in tissues and concentrative uptake
      mechanism for a cationic compound of DX-9065a in rats. After a single intravenous
      dosing of [(14)C]-DX-9065a to male rats, higher levels of radioactivity were
      observed in kidney and liver. Moreover, the radioactivity in the liver
      continuously increased up to 6 h after intravenous dosing and a concentrative
      uptake of the drug against the radioactivity gradient between plasma and liver,
      showing K(p) value of 90.7. In contrast, carrier-mediated systems did not play a
      significant role in the uptake of DX-9065a by hepatocytes. A subcellular
      distribution study was conducted by means of Percoll density gradient
      centrifugation and revealed a high affinity of the compound with the lysosomes.
      It was concluded that DX-9065a permeated into hepatocyte across the membrane
      primarily by passive diffusion, and the consequent process of lysosomal trapping
      played a major role in the concentrative uptake of the drug into the liver.

PMID- 16795023
TI  - Study of Pax6 mutant rat revealed the association between upper incisor formation
      and midface formation.
AB  - In this study, we investigated the process of supernumerary upper incisor
      formation in the Pax6 mutant rat, rSey(2)/rSey(2), which exhibits a facial cleft
      between the medial nasal and maxillary processes. Histological investigation and
      epithelial labeling studies of wild type rat embryos indicated that the upper
      incisor develops by fusion of two primary dental placodes (PDPs) in the medial
      nasal process with a contribution from the epithelium of the maxillary process.
      In the rSey(2)/rSey(2) embryo, both PDPs are formed but they stay apart, then
      subsequently these PDPs independently develop into upper incisor tooth buds. In
      order to examine if the failure of the two placodes to fuse is due to the cleft
      between the maxillary and medial nasal processes, maxillary and medial nasal
      process fusion was inhibited with a barrier in wild type embryos. This resulted
      in the maintenance of the two distinct PDPs. These results demonstrate that
      fusion of the facial processes reduces the number of odontogenic placodes and is
      required to assemble all components at one site for rat upper incisor formation.
      The results also provide further insight into the mechanism of supernumerary
      incisor formation in human cleft lip conditions.

PMID- 16795024
TI  - Phase behavior of beta hydroxy-acids with laureth 4.
AB  - The colloidal structures of beta carboxylic acid topical vesicle formulations
      were determined and the changes during evaporation after applications were
      estimated from phase diagrams. The results showed significant difference during
      evaporation between salicylic acid on one hand and three water soluble acids;
      malic, tartaric, and citric acid, on the other. The water soluble acids showed an
      increase in the acid concentration in the aqueous solution to levels that must be
      considered harmful, while salicylic acid showed no increase in concentration in
      the individual phases even after 99% evaporation of water.

PMID- 16795025
TI  - Superficial temporal artery as an external landmark for deeper-lying brain
      structures.
AB  - Additional localizing superficial landmarks for intracranial structures can be of
      use to the neurosurgeon. This study was performed to evaluate the usefulness of
      the superficial temporal artery (STA) as an external landmark for deeper brain
      structures. Thirteen adult cadavers (26 sides) underwent latex injection of their
      STA bilaterally. Dissections were next carried out to identify this vessel. Once
      the STA and its frontal and parietal branches were skeletonized, craniectomies
      were performed and the underlying dura mater excised. Measurements were made
      between the frontal and parietal branches of the STA and deeper brain structures.
      The STA was found to branch on average 3 cm superior to the tragus. The
      bifurcation of the STA was found to commonly bifurcate at the level of the floor
      of the middle cranial fossa or superior temporal gyrus. The Sylvian fissure was
      found at a mean of 2 cm superior to the STA bifurcation. The angle between the
      frontal branch of the STA and the zygomatic arch had a mean of 37 degrees. The
      angle between the frontal and parietal branches of the STA had a mean of 87
      degrees. At the level of the glabella, the frontal branch of the STA was on
      average 3 cm posterior to the frontal pole. The temporal tip was located a mean
      of 3.2 cm anterior to the frontal branch of the STA. The plane of the foramen of
      Monro was found to lie at a mean distance of 2.3 cm posterior to the frontal
      branch of the STA. The parietal branch of the STA was noted to travel more or
      less parallel with the central sulcus in all specimens and to travel an average
      of 2 cm posterior to this sulcus. At the level of the lateral attachment of the
      tentorium cerebelli, the parietal branch of the STA was found to travel a mean of
      4.8 cm anterior to the entrance of the vein of Labbe into the transverse sinus.
      The parietal branch of the STA was also found to travel a mean of 4.2 cm anterior
      to the angular gyrus and 3.9 cm anterior to the supramarginal gyrus. Palpation or
      Doppler identification of the STA and its branches with subsequent mapping on the
      lateral cranium may prove useful as an additional superficial landmark for the
      neurosurgeon.

PMID- 16795026
TI  - A case of a cilioretinal artery supplying the entire retina.
AB  - The cilioretinal artery commonly supplies a small area of the retina, usually the
      macula. It can serve a valuable purpose in preserving the central vision in
      central retinal artery occlusion. We describe a case, where the total retinal
      circulation is from the cilioretinal artery in one eye and an abnormal central
      retinal artery branching in the other eye. The clinical relevance of cilioretinal
      artery in the eye is discussed.

PMID- 16795027
TI  - The impact of alternating dissection on student performance in a medical anatomy
      course: are dissection videos an effective substitute for actual dissection?
AB  - The way in which anatomy is taught to first year medical students at the
      University of North Carolina at Chapel Hill was recently changed, so that first
      year students are now divided into two groups that dissect alternately. The
      effect of this change on both written and practical test performance was analyzed
      by comparing grades from 2004 with those from the previous year (2003), when
      students performed all the dissections. A statistically significant decrease (P <
      or = 0.05) from 2003 was noted on three of the four written test scores in 2004,
      while practical examination scores in 2004 fluctuated from lower to higher than
      those in 2003, depending on the unit of material being covered. However, the
      number of students failing each of the examinations (written and practical
      combined) was statistically greater on only one of the four examinations in 2004.
      Scores of the two groups dissecting alternately in 2004 were essentially the same
      on the practical examinations. There was no difference in the number of questions
      answered incorrectly between these two groups in the two practical examinations
      where comparisons were made. Furthermore, students who dissected a particular
      structure did not score significantly better on practical questions concerning
      that structure than students who had not dissected it. The effect of the
      availability of step-by-step dissection videos on student practical examination
      scores is also discussed. We conclude that the change in the curriculum had a
      significant impact on the students' written examination performance, given the
      same material in the course. The reasons for this include student course load,
      increased need for self-study, and a loss of a learning opportunity in the
      dissection laboratory, all of which affect student comprehension and retention of
      the material and their ability to use it in problem solving.

PMID- 16795028
TI  - The contributions of the Bartholin family to the study and practice of clinical
      anatomy.
AB  - Between 1585 and 1738, four members of the celebrated Bartholin family made
      significant contributions to anatomical science and medicine. Caspar Bartholin
      (the elder), two of his sons (Thomas and Rasmus), and his grandson (Caspar the
      younger) all served on the medical faculty of the University of Copenhagen, and
      helped to gain international acclaim for the institution. Over three generations,
      the Bartholins challenged traditional ideas about science and the human body, and
      discovered anatomical structures and phenomena that would prove crucial to the
      practice of modern medicine.

PMID- 16795029
TI  - Three-dimensional CT angiography: a new technique for imaging microvascular
      anatomy.
AB  - To date there has been no satisfactory research method for imaging microvascular
      anatomy in three dimensions (3D). In this article we present a new technique that
      allows both qualitative and quantitative examination of the microvasculature in
      3D. In 10 fresh cadavers (7 females, 3 males, mean age 68 years), selected
      arteries supplying the abdominal wall and back were injected with a lead
      oxide/gelatin contrast mixture. From these regions, 30 specimens were dissected
      free and imaged with a 16-slice spiral computed tomographic (CT) scanner. Using
      three-dimensional CT (3D-CT) angiography, reconstructions of the microvasculature
      of each specimen were produced and examined for their qualitative content. Two
      calibration tools were constructed to determine (1) the accuracy of linear
      measurements made with CT software tools, and (2) the smallest caliber blood
      vessel that is reliably represented on 3D-CT reconstructions. Three-dimensional
      CT angiography produced versatile, high quality angiograms of the
      microvasculature. Correlation between measurements made with electronic calipers
      and CT software tools was very high (Lin's concordance coefficient, 0.99 (95% CI
      0.99-0.99)). The finest caliber of vessel reliably represented on the 3D-CT
      reconstructions was 0.4 mm internal diameter. In summary, 3D-CT angiography is a
      simple, accurate, and reproducible method that imparts a much improved perception
      of anatomy when compared with existing research methods. Measurement tools
      provide accurate quantitative data to aid vessel mapping and preoperative
      planning. Further work will be needed to explore the full utility of 3D-CT
      angiography in a clinical setting.

PMID- 16795030
TI  - Fiber type composition and maximum shortening velocity of muscles crossing the
      human shoulder.
AB  - A study of the fiber type composition of fourteen muscles spanning the human
      glenohumeral joint was carried out with the purpose of determining the
      contribution of fiber types to overall muscle cross-sectional area (CSA) and to
      estimate the maximum shortening velocity (V(max)) of those muscles. Muscle
      biopsies were procured from 4 male cadavers (mean age 50) within 24 hr of death,
      snap frozen, mounted, and transversely sectioned (10 microm). Slides were stained
      for myofibrillar ATPase after alkaline preincubation. Photoimages were taken of
      defined areas (100 fibers) using the Bioquant system, and fiber type and CSA were
      measured from these images. Staining for mATPase produced three different fiber
      types: slow-oxidative (SO), fast-oxidative-glycolytic (FOG), and fast-glycolytic
      (FG). On average, the muscle fiber type composition ranged from 22 to 40% of FG,
      from 17 to 51% of FOG, and from 23 to 56% of SO. Twelve out of the 14 muscles had
      average SO proportions ranging from 35 to 50%. V(max) was calculated from the
      fiber type contribution relative to CSA and shortening velocity values taken from
      the literature. The maximum velocities of shortening presented here provide a
      physiological basis for the development of human shoulder musculoskeletal models
      suitable for predicting muscle forces for functionally relevant tasks
      encompassing conditions of muscle shortening and lengthening.

PMID- 16795031
TI  - Morphometric study of the human metatarsals and phalanges.
AB  - Mathematical relation between metatarsals and between phalanges in terms of their
      lengths and widths in themselves is considered to be significant with respect to
      its functional and aesthetic roles. The objective of this study is to conduct
      measurements for determining lengths and widths of metatarsals and phalanges on
      the foot radiographs and to determine possible mathematical correlations between
      metatarsals themselves and between phalanges themselves in terms of their lengths
      and widths. Anteroposterior right and left foot radiographs were taken from 100
      volunteers (50 men and 50 women). Lengths and widths of the metatarsals and
      phalanges were measured in millimeter on radiographs. The mean, minimum and
      maximum values, and standard deviations of each bone's length and width were
      studied and data were put into formulation. The results were evaluated by
      Regression statistical test, and the relation between metatarsals and between
      phalanges in terms of their lengths and widths was studied. As a result of the
      measurements, we found fixed proportions between metatarsals in themselves and
      between phalanges in themselves in terms of their lengths and widths. Knowing
      these morphometric relations may be useful for performing any surgical procedures
      designed to manage any defects or imperfections of the foot, chief among them is
      shortness.

PMID- 16795032
TI  - Photodynamic cell-kill analysis of breast tumor cells with a tamoxifen
      pyropheophorbide conjugate.
AB  - We hypothesized that estrogen receptor (ER) in hormone-sensitive breast cancer
      cells could be targeted for selective photodynamic killing of tumor cell with
      antiestrogen-porphyrin conjugates by combining the over-expression of ER in
      hormone-sensitive breast cancer cells and tumor-retention property of porphyrin
      photosensitizers. In this study we describe that a tamoxifen (TAM)
      pyropheophorbide conjugate that specifically binds to ER alpha, caused selective
      cell-kill in MCF-7 breast cancer cells upon light exposure. Therefore, it is a
      potential candidate for ER-targeted photodynamic therapy of cancers (PDT) of
      tissues and organs that respond to estrogens/antiestrogens.

PMID- 16795033
TI  - Effects of antisense mediated inhibition of cathepsin K on human osteoclasts
      obtained from peripheral blood.
AB  - Cathepsin K is a cystein protease that displays a proteolytic activity against
      Type I collagen and is abundantly and selectively expressed in osteoclasts where
      it plays a critical role in bone degradation. Its direct role in bone tissue has
      been defined by knock-out mice studies and inhibiting strategies in animals
      models. However, direct proof of cathepsin K function in human osteoclast model
      in vitro is lacking. The aim of this study is to analyze cathepsin K expression
      and localization in human osteoclasts obtained from peripheral blood and to
      examine cathepsin K function in these cells by antisense oligodeoxynucleotide (AS
      ODN) strategy. AS-ODN was added to the culture of osteoclast precursors induced
      to differentiate by RANKL and M-CSF. AS-ODN treatment produced a significant down
      regulation of cathepsin K mRNA (>80%) and protein expression, as verified
      respectively by Real-time PCR and by immunocytochemistry or Western blot. The
      cathepsin K inhibition caused an impairment of resorption activity as evaluated
      by a pit formation assay ( p = 0.045) and by electron microscopy, while the
      acidification process was unaffected. We demonstrated that antisense strategies
      against cathepsin K are selectively effective to inhibit resorption activity in
      human osteoclasts, like in animal models.

PMID- 16795034
TI  - Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord
      vein endothelial cells through an IL-1-dependent mechanism.
AB  - Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both low
      molecular-weight lysophospholipid (LPL) ligands which are recognized by the Edg
      family of G protein-coupled receptors (GPCRs). In endothelial cells, these two
      ligands activate Edg receptors resulting in cell proliferation and cell
      migration. Interleukin-8 (IL-8) is a C-X-C chemokine and acts as a
      chemoattractant of neutrophils, whereas monocyte chemoattractant protein-1 (MCP
      1) is a C-C chemokine and functions mainly as a chemoattractant of
      monocytes/macrophages. Both factors are secreted from endothelial cells and have
      been implicated in the processes leading to atherosclerosis. We examined the
      effects of LPLs on the expression of IL-8 and MCP-1, key regulators of leukocyte
      recruitment in human umbilical cord vein endothelial cells (HUVECs). Work
      illustrated in this article showed that LPA and S1P enhanced IL-8 and MCP-1 mRNA
      expressions, and protein secretions in dose- and time-dependent fashions. Maximal
      mRNA expression appeared at 16 hr post-ligand treatment. Using prior treatments
      with chemical inhibitors, LPLs enhanced IL-8 and MCP-1 expressions through a Gi-,
      Rho-, and NFkappaB-dependent mechanism. In a chemotaxis assay system, LPL
      treatments of endothelial cells enhanced monocyte recruitment through
      upregulating IL-8 and MCP-1 protein secretions. Pre-incubation with AF12198, an
      IL-1 receptor antagonist or IL-1 functional blocking antibody both suppressed the
      enhanced effects elicited by LPLs of IL-8 and MCP-1 mRNA expressions in HUVECs.
      These results suggest that LPLs released by activated platelets might enhance the
      IL-8- and MCP-1-dependent chemoattraction of monocytes toward the endothelium
      through an IL-1-dependent mechanism, which may play an important role in
      facilitating wound-healing and inflammation processes.

PMID- 16795036
TI  - Okadaic acid induces phosphorylation of p65NF-kappaB on serine 536 and activates
      NF-kappaB transcriptional activity in human osteoblastic MG63 cells.
AB  - Nuclear factor-kappa B (NF-kappaB) is an essential transcription factor in the
      control of expression of genes involved in cell growth, differentiation,
      inflammation, and neoplastic transformation. Previously, we reported that okadaic
      acid (OA), which is a specific inhibitor of serine/threonine protein
      phosphatases, induced apoptosis in cells of human osteosarcoma cell line MG63.
      However, to date, it is not clear whether the phosphorylation status of NF-kappaB
      could be affected by the treatment with OA. In this report, we demonstrate that
      treatment of MG63 cells with OA enhanced the phosphorylation level of NF-kappaB,
      as judged from the results of Western blot analysis and a lambda protein
      phosphatase dephosphorylation assay. The phosphorylation level of NF-kappaB was
      enhanced in both time- and dose-dependent manners. In the cells treated with 100
      nM OA for 3 h, consequential translocation of NF-kappaB from the cytosol to the
      nucleus occurred. Western blotting experiments with an anti-phospho-p65NF-kappaB
      antibody disclosed that the NF-kappaB was phosphorylated on serine 536.
      Furthermore, OA stimulated the transcriptional activity of NF-kappaB in MG63
      cells, as judged from the results of a luciferase assay. Our findings indicate
      that OA elicit phosphorylation of NF-kappaB on serine 536 in MG63 cells,
      resulting in the translocation of phospho-NF-kappaB to the nucleus, thereby
      promoting transcriptional activity of genes.

PMID- 16795035
TI  - A limited number of genes are involved in the differentiation of germinal center
      B cells.
AB  - Mature B cells, upon activation, progressively differentiate through centroblasts
      into centrocytes and finally to plasmacytes that express large amounts of
      selected immunoglobulins. A significant part of this maturation is thought to
      involve induction of the unfolded protein response (UPR). We have compared gene
      expression in normal germinal center centroblasts, centrocytes, lymphoblastoid
      cells undergoing induced UPR, and the CCL155 plasmacytoma cell line. In the
      centroblast to centrocyte transition there is a change in the expression of a
      relatively small number of genes. These include a limited subset of the genes
      upregulated by a fully activated UPR as well as a small number of other
      transcription factors, some disulphide isomerases, and other genes. This is
      consistent with a model in which this transition is mediated by changes in the
      levels of expression of transcription factor B-lymphocyte-induced maturation
      protein 1 (Blimp1) (PRDM1), BACH2, X-box binding protein 1 (XBP1), interferon
      regulatory factor 4 (IRF4), and possibly vitamin D receptor (VDR) expression,
      together with post-transcriptional changes and a limited induction of aspects of
      the UPR.

PMID- 16795037
TI  - Gene expression profiles of normal proliferating and differentiating human
      intestinal epithelial cells: a comparison with the Caco-2 cell model.
AB  - cDNA microarray technology enables detailed analysis of gene expression
      throughout complex processes such as differentiation. The aim of this study was
      to analyze the gene expression profile of normal human intestinal epithelial
      cells using cell models that recapitulate the crypt-villus axis of intestinal
      differentiation in comparison with the widely used Caco-2 cell model. cDNA
      microarrays (19,200 human genes) and a clustering algorithm were used to identify
      patterns of gene expression in the crypt-like proliferative HIEC and tsFHI cells,
      and villus epithelial cells as well as Caco-2/15 cells at two distinct stages of
      differentiation. Unsupervised hierarchical clustering analysis of global gene
      expression among the cell lines identified two branches: one for the HIEC cells
      versus a second comprised of two sub-groups: (a) the proliferative Caco-2 cells
      and (b) the differentiated Caco-2 cells and closely related villus epithelial
      cells. At the gene level, supervised hierarchical clustering with 272
      differentially expressed genes revealed distinct expression patterns specific to
      each cell phenotype. We identified several upregulated genes that could lead to
      the identification of new regulatory pathways involved in cell differentiation
      and carcinogenesis. The combined use of microarray analysis and human intestinal
      cell models thus provides a powerful tool for establishing detailed gene
      expression profiles of proliferative to terminally differentiated intestinal
      cells. Furthermore, the molecular differences between the normal human intestinal
      cell models and Caco-2 cells clearly point out the strengths and limitations of
      this widely used experimental model for studying intestinal cell proliferation
      and differentiation.

PMID- 16795038
TI  - Gene expression alterations in activated human T-cells induced by modeled
      microgravity.
AB  - Studies conducted in real Space and in ground-based microgravity analog systems
      (MAS) have demonstrated changes in numerous lymphocyte functions. In this
      investigation we explored whether the observed functional changes in lymphocytes
      in MAS are associated with changes in gene expression. NASA-developed Rotating
      Wall Vessel (RWV) bioreactor was utilized as a MAS. Activated T lymphocytes were
      obtained by adding 100 ng/ml of anti-CD3 and 100 U/ml of IL-2 in RPMI medium to
      blood donor mononuclear cells for 4 days. After that the cells were washed and
      additionally cultured for up to 2 weeks with media (RPMI, 10% FBS and 100 U/ml IL
      2) replacement every 3-4 days. Flow cytometry analysis had proven that activated
      T lymphocytes were the only cells remaining in culture by that time. They were
      split into two portions, cultured for additional 24 h in either static or
      simulated microgravity conditions, and used for RNA extraction. The gene
      expression was assessed by Affymetrix GeneChip Human U133A array allowing
      screening for expression of 18,400 genes. About 4-8% of tested genes responded to
      MG by more than a 1.5-fold change in expression; however, reproducible changes
      were observed only in 89 genes. Ten of these genes were upregulated and 79 were
      downregulated. These genes were categorized by associated pathways and viewed
      graphically through histogram analysis. Separate histograms of each pathway were
      then constructed representing individual gene expression fold changes. Possible
      functional consequences of the identified reproducible gene expression changes
      are discussed.

PMID- 16795039
TI  - Comparison of various kinds of bone marrow stem cells for the repair of infarcted
      myocardium: single clonally purified non-hematopoietic mesenchymal stem cells
      serve as a superior source.
AB  - A variety of adult stem cells have been used to transplant into the infarcted
      (MI) heart, however, comparative studies are lacking to show more suitable source
      of cells for transplantation. We have identified a single non-hematopoietic
      mesenchymal stem cell subpopulation (snMSCs) isolated from human bone marrow and
      clonally purified, that over 99% of them expressed MSC marker proteins and
      cardiomyocyte marker proteins when induction in vitro. We also compared the
      effects of the snMSCs with unpurified MSC (uMSCs), mononuclear cells (BMMNCs), or
      peripheral blood mononuclear cells (PBMNCs) on myocardial repair after induction
      of MI in rats. Ninety days later, we observed a better cardiac function assessed
      by ejection fraction, fraction of shortening and lung wet/dry weight ratios, less
      remodeling of left ventricle (LV), lower collagen density in the LV, and more
      vessels in the ischemic wall in the snMSCs transplantation group than in other
      cell-transplanted groups. Furthermore, the transplanted cells expressing
      cardiomyocyte specific proteins or vascular endothelial cell marker proteins were
      more in the snMSCs group than in other ones. We conclude that transplantation
      with single clonally purified MSCs seems to be more beneficial to the cardiac
      repair than with other stem cells after MI.

PMID- 16795040
TI  - Effects of histone deacetylase inhibitors on p55CDC/Cdc20 expression in HT29 cell
      line.
AB  - In a previous work, taking advantage of the gene-array screening technology, we
      analysed the effects of histone deacetylase (HDAC) inhibitor sodium butyrate
      (NaBt), on gene transcription in HT29 human adenocarcinoma cell line. In this
      study, we focused our attention on p55CDC/Cdc20 gene, whose expression was
      dramatically reduced by NaBt treatment. Mammalian p55CDC/Cdc20 interacts with the
      anaphase promoting complex/cyclosome (APC/C), and is involved in regulating
      anaphase onset and late mitotic events. Using NaBt and trichostatin A (TSA), a
      member of the HDAC inhibitor family, we showed that both HDAC inhibitors totally
      downregulated p55CDC/Cdc20 transcription and expression. Cell cycle analysis
      demonstrated that NaBt arrested HT29 cells in G0/G1 phase, while TSA caused a
      double block in G0/G1 and G2/M phases. Moreover, p55CDC/Cdc20 showed maximal
      expression in S and G2/M phases of HT29 cell division cycle. Based on this
      evidence, and by means of specific cell cycle modulators, such as nocodazole and
      hydroxyurea, we demonstrated that both TSA and NaBt were responsible for loss of
      p55CDC/Cdc20 expression, but with different mechanisms of action. Taken together,
      these results suggest that targeting molecules involved in spindle mitotic
      checkpoint, such as p55CDC/Cdc20, might account for the high cytotoxicity of HDAC
      inhibitors versus malignant cells.

PMID- 16795041
TI  - Ochnaflavone inhibits TNF-alpha-induced human VSMC proliferation via regulation
      of cell cycle, ERK1/2, and MMP-9.
AB  - Ochnaflavone (c-3 of apigenin-0-c-4 of apigenin; OC), a biflavonoid present in
      the human diet, is known to inhibit angiotensin II-induced hypertrophy and serum
      induced smooth muscle cell proliferation. OC is known to have anti-fungal and
      anti-inflammatory activities. However, it is not known whether OC exerts similar
      cardioprotective effects in cells treated with tumor necrosis factor (TNF)-alpha.
      In this study, we isolated OC from Lonicera japonica and studied its effect on
      matrix metalloproteinase-9 (MMP-9) gene expression in human aortic smooth muscle
      cells (HASMC). Furthermore, we investigated whether OC exerts the multiple
      suppressive effects on cytokine TNF-alpha-induced HASMC. Treatment of OC showed
      its potent inhibitory effects on DNA synthesis of cultured HASMC in the presence
      of TNF-alpha. These inhibitory effects were associated with reduced extracellular
      signal-regulated kinase 1/2 (ERK1/2) activity and G1 cell cycle arrest. Treatment
      of OC, which induced a cell cycle block in G1-phase, induced downregulation of
      cyclins and CDKs and upregulation of the CDK inhibitor p21(waf1) expression,
      whereas upregulation of p27 or p53 by OC was not observed. Because anti
      atherogenic effects need not be limited to anti-proliferation, we decided to
      examine whether OC exerts inhibitory effects on MMP-9 activity in TNF-alpha
      induced HASMC. OC inhibited TNF-alpha-induced MMP-9 secretion on HASMC in a dose
      dependent manner. This inhibition was characterized by downregulation of MMP-9,
      which was transcriptionally regulated at nuclear factor (NF)-kappaB site and
      activation protein (AP)-1 site in the MMP-9 promoter. These findings indicate the
      efficacy of OC in inhibiting cell proliferation, G1 to S-phase cell cycle
      progress, and MMP-9 expression through the transcription factors NF-kappaB and AP
      1 on TNF-alpha-induced HASMC. The findings of the present study may provide a
      potential mechanism that explains the anti-atherogenic activity of OC.

PMID- 16795042
TI  - Inhibition of human breast cancer cell (MBA-MD-231) invasion by the Ea4-peptide
      of rainbow trout pro-IGF-I.
AB  - It was shown previously that Ea4-peptide of trout pro-IGF-I exerted mitogenic
      activity in non-transformed cells and inhibited colony formation in a soft agar
      medium of established human cancer cells. Here we report that the same peptide
      inhibits the invasion of human breast cancer cells (MDA-MB-231) through a
      matrigel membrane in a dose-dependent manner. The expression of urokinase-type
      plasminogen activator (uPA), tissue-type plasminogen activator (tPA) and
      plasminogen activator inhibitor 1 (PAI1) genes in MDA-MB-231 cells were
      downregulated by treatment with rtEa4-peptide. The inhibition of expression of
      these genes in response to rtEa4-peptide treatment was reduced to the control
      level when inhibitors for c-Jun N-terminal kinase 1/2 (JNK1/2), mitogen activated
      protein kinase kinase 1/2 (Mek1/2), p38 mitogen activated protein kinase (p38
      MAPK), phosphatidylinositol 3-kinase (PI3K), and phosphokinase C (PKC) were used.
      These results suggest that inhibition of invasion of MDA-MB-231 cells by rtEa4
      peptide may be mediated via the suppression of uPA, tPA, and PAI1 gene activities
      through signal transduction pathways.

PMID- 16795043
TI  - Regulation of Sam68 activity by small heat shock protein 22.
AB  - Sam68 associates with c-Src kinase during mitosis. We previously demonstrated
      that Sam68 functionally replaces and/or synergizes with HIV-1 Rev in rev response
      element (RRE)-mediated gene expression and virus production. Furthermore, we
      reported that knockdown of Sam68 inhibited Rev-mediated RNA export and it is
      absolutely required for HIV-1 production. In the present study, we identified
      small heat shock protein, hsp22, as a novel interacting partner of Sam68. Hsp22
      binds to Sam68 in vitro and in vivo. Overexpression of hsp22 significantly
      inhibits Sam68-mediated RRE- as well as CTE (constitutive transport element)
      dependent reporter gene expression. Furthermore, exposing 293T cells to heat
      shock inhibits Sam68/RRE function by virtue of elevating hsp22. The critical
      domain of hsp22 that interacts with Sam68 resides between amino acids 62 and 133.
      Our studies provide evidence for the first time that hsp22 specifically binds to
      Sam68 and modulates its activity, thus playing a role in the post-transcriptional
      regulation of gene expression.

PMID- 16795044
TI  - Methods for measuring rates of protein binding to insoluble scaffolds in living
      cells: histone H1-chromatin interactions.
AB  - Understanding of cell regulation is limited by our inability to measure molecular
      binding rates for proteins within the structural context of living cells, and
      many systems biology models are hindered because they use values obtained with
      molecules binding in solution. Here, we present a kinetic analysis of GFP-histone
      H1 binding to chromatin within nuclei of living cells that allows both the
      binding rate constant k(ON) and dissociation rate constant k(OFF) to be
      determined based on data obtained from fluorescence recovery after photobleaching
      (FRAP) analysis. This is accomplished by measuring the ratio of bound to free
      concentration of protein at steady state, and identifying the rate-determining
      step during FRAP recovery experimentally, combined with mathematical modeling. We
      report k(OFF) = 0.0131/s and k(ON) = 0.14/s for histone H1.1 binding to
      chromatin. This work brings clarity to the interpretation of FRAP experiments and
      provides a way to determine binding kinetics for nuclear proteins and other
      cellular molecules that interact with insoluble scaffolds within living cells.

PMID- 16795046
TI  - Cyclic tensile stretch load and oxidized low density lipoprotein synergistically
      induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes,
      resulting in decreased cell viability and proteoglycan synthesis.
AB  - Mechanical stimulation is known to be an essential factor in the regulation of
      cartilage metabolism. We tested the hypothesis that expression of lectin-like
      oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic
      tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress
      at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1
      to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the
      addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times
      control). Application of the cyclic load to the chondrocytes along with 10
      microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3
      times control. Individual application of cyclic loading and 10 microg/mL ox-LDL
      significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/-
      3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan
      synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p
      < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading
      and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan
      synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/-
      6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with
      individual application of cyclic loading or 10 microg/mL ox-LDL). In this study,
      we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on
      cell viability and proteoglycan synthesis in chondrocytes, which may be mediated
      through enhanced expression of LOX-1 and which has important implications in the
      progression of cartilage degeneration in osteoarthritis.

PMID- 16795045
TI  - Biologic properties of mesenchymal stem cells derived from bone marrow and
      adipose tissue.
AB  - The biologic characteristics of mesenchymal stem cells (MSCs) isolated from two
      distinct tissues, bone marrow and adipose tissue were evaluated in these studies.
      MSCs derived from human and non-human primate (rhesus monkey) tissue sources were
      compared. The data indicate that MSCs isolated from rhesus bone marrow (rBMSCs)
      and human adipose tissue (hASCs) had more similar biologic properties than MSCs
      of rhesus adipose tissue (rASCs) and human bone marrow MSCs (hBMSCs). Analyses of
      in vitro growth kinetics revealed shorter doubling time for rBMSCs and hASCs.
      rBMSCs and hASCs underwent significantly more population doublings than the other
      MSCs. MSCs from all sources showed a marked decrease in telomerase activity over
      extended culture; however, they maintained their mean telomere length. All of the
      MSCs expressed embryonic stem cell markers, Oct-4, Rex-1, and Sox-2 for at least
      10 passages. Early populations of MSCs types showed similar multilineage
      differentiation capability. However, only the rBMSCs and hASCs retain greater
      differentiation efficiency at higher passages. Overall in vitro characterization
      of MSCs from these two species and tissue sources revealed a high level of common
      biologic properties. However, the results demonstrate clear biologic
      distinctions, as well.

PMID- 16795047
TI  - Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone
      regeneration in a segmental defect in the ovine tibia: pilot study.
AB  - Limitations in the use of autologous bone graft, which is the gold standard
      therapy in bone defect healing, drive the search for alternative treatments. In
      this study the influence of rhTGFbeta-3 on mechanical and radiological parameters
      of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm
      long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a
      poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was
      treated by the carrier only, in a third group (n = 4) by autologous cancellous
      bone graft, and in a fourth group (n = 2) the defect remained blank. The healing
      process of the defect was assessed by weekly in vivo stiffness measurements and
      radiology as well as by quantitative computed tomographic assessment of bone
      mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks
      under loading conditions. In the bone graft group, a marginally significant
      higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p =
      0.06) and a significantly higher increase than in the PLA-only group (p = 0.03).
      The radiographic as well as the computed tomographic evaluation yielded
      significant differences between the groups (p = 0.03), indicating the bone graft
      treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the
      PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09
      g/cm(3)), respectively. Regarding the mechanical and radiological parameters
      assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on
      bone regeneration. However, under the conditions of this study, this effect does
      not reach the potential of autologous cancellous bone graft transplantation.

PMID- 16795048
TI  - Fibronectin enhances in vitro vascular calcification by promoting osteoblastic
      differentiation of vascular smooth muscle cells via ERK pathway.
AB  - The process of vascular calcification presents several features similar to
      osteogenesis in which fibronectin (FN) acts as a regulator of osteoblastic
      differentiation and the ERK signal pathway is involved. In order to find whether
      FN promotes the osteoblastic differentiation of vascular smooth muscle cells
      (VSMCs) through the ERK signal pathway, we investigated the effect of FN on the
      calcification of VSMCs by using an in vitro cell model. VSMCs cultured in plates
      with FN (0-20 microg/cm2) coating were induced to calcify by 10 mM sodium beta
      glycerophosphate (beta-GP). FN exacerbated VSMC calcification in a dose- and time
      dependent manner, as indicated by the number of calcifying nodules per slide and
      the amount of calcium in the deposition. Data from RT-PCR and immunoblotting
      assay revealed that FN also enhanced the expression of several phenotypic markers
      of osteoblasts, including alkaline phosphatase (ALP) activity, osteocalcin (OC),
      and Osf2/Cbfa1, a key transcription factor in osteoblastic differentiation.
      Furthermore, a specific inhibitor for ERK, PD98059 (10 microM), significantly
      suppressed the effect of FN on calcification and phenotypic marker expression.
      These findings seem to suggest that FN enhanced vascular calcification by
      promoting the osteoblastic differentiation of VSMCs via ERK signal pathway.

PMID- 16795049
TI  - Regulation of osteoblast differentiation by transcription factors.
AB  - Runx2, osterix, and beta-catenin are essential for osteoblast differentiation.
      Runx2 directs multipotent mesenchymal cells to an osteoblastic lineage, and
      inhibits them from differentiating into the adipocytic and chondrocytic lineages.
      After differentiating to preosteoblasts, beta-catenin, osterix, and Runx2 direct
      them to immature osteoblasts, which produce bone matrix proteins, blocking their
      potential to differentiate into the chondrocytic lineage. Runx2 inhibits
      osteoblast maturation and the transition into osteocytes, keeping osteoblasts in
      an immature stage. Other transcription factors including Msx1, Msx2, Dlx5, Dlx6,
      Twist, AP1(Fos/Jun), Knox-20, Sp3, and ATF4 are also involved in osteoblast
      differentiation. To gain an understanding of bone development, it is important to
      position these transcription factors to the right places in the processes of
      osteoblast differentiation.

PMID- 16795050
TI  - Modifications of nuclear architecture and chromatin organization in ataxia
      telangiectasia cells are coupled to changes of gene transcription.
AB  - Ataxia telangiectasia (AT) is a rare genetic disorder caused by mutations of ATM
      gene. ATM kinase is a "master controller" of DNA-damage response and signal
      transducer of external stimuli. The complex role of ATM may explain the
      pleiotropic phenotype characteristic of AT syndrome, only partially. In our
      hypothesis, the multi-faceted phenotype of AT patients might depend on specific
      chromatin reorganization, which then reflects on the cellular transcription. We
      analyzed three lymphoblastoid cell-lines isolated from AT patients and one
      healthy control. The three-dimensional reconstruction disclosed marked changes of
      nuclear morphology and architecture in AT cells. When chromatin condensation was
      analyzed by differential scanning calorimetry, a remodeling was observed at the
      level of fiber folding and nucleosome conformation. Despite the structural
      differences, chromatin did not exhibit modifications of the average acetylation
      status in comparison to the control. Moreover, AT cells presented significant
      alterations in the transcription of genes involved in cell-cycle regulation and
      stress response. In AT3RM cells, the average chromatin decondensation went with
      the upregulation of c-fos, c-jun, and c-myc and downregulation of
      metallothioneins, p21 and p53. AT9RM and AT44RM cells were instead characterized
      by an increased chromatin condensation and presented a different transcription
      unbalance. Whereas in AT44RM all the considered genes were downregulated, in
      AT3RM the three oncogenes and metallothioneins were upregulated, but p53 and p21
      were downregulated.

PMID- 16795051
TI  - Mitochondrial calcium transport is regulated by P2Y1- and P2Y2-like mitochondrial
      receptors.
AB  - Ischemia-reperfusion injury remains a major clinical problem in liver
      transplantation. One contributing factor is mitochondrial calcium (mCa(2+))
      overload, which triggers apoptosis; calcium also regulates mitochondrial
      respiration and adenosine 5'-triphosphate (ATP) production. Recently, we reported
      the presence of purinergic P2Y(1)- and P2Y(2)-like receptor proteins in
      mitochondrial membranes. Herein, we present an evaluation of the functional
      characteristics of these receptors. In experiments with isolated mitochondria,
      specific P2Y(1) and P2Y(2) receptors ligands: 2-methylthio-adenosine 5'
      diphosphate (2meSADP) and uridine 5'-triphosphate (UTP), respectively, were used,
      and mitochondrial calcium uptake was measured. 2meSADP and UTP had a maximum
      effect at concentrations in the range of the known P2Y(1) and P2Y(2) receptors.
      The P2Y inhibitor phosphate-6-azophenyl-2',4'-disulfonate (PPADS) blocked the
      effects of both ligands. The phospholipase C (PLC) antagonist U73122 inhibited
      the effect of both ligands while its inactive analog U73343 had no effect. These
      data strongly support the hypothesis that mitochondrial Ca(2+) uptake is
      regulated in part by adenine nucleotides via a P2Y-like receptor mechanism that
      involves mitochondrial PLC activation.

PMID- 16795053
TI  - Chromosome organization and gene control: it is difficult to see the picture when
      you are inside the frame.
AB  - The organization of the genome in the nucleus is related to its function. The
      functional compartmentalization of the genome is described at the nuclear,
      chromosomal, subchromosomal, nucleosomal, and DNA sequence level. These
      descriptions originate from the techniques that were used for analysis. The
      different levels of compartmentalization are not easily reconciled, because the
      techniques applied to identify genome compartmentalization generally cannot be
      performed in combination. We have obtained a large body of information on
      individual "actors" and "scenes" in the nucleus regarding genome
      compartmentalization, but we still do not understand how and by what pieces of
      equipment the "actors" play their game. The next challenge is to understand the
      combined operation of the various levels of functional genome organization in the
      nucleus, that is, how do the epigenetic and genetic levels act together. In this
      paper, I will highlight some of the general features and observations of
      functional organization of the eukaryotic genome in interphase nuclei and discuss
      the concepts and views based on observed correlations between genome organization
      and function. I will reflect on what is to be expected from this field of
      research when the functional levels of genome compartmentalization are
      integrated. In this context I will draw attention to what might be needed to
      improve our understanding.

PMID- 16795052
TI  - Novel putative targets of N-ethylmaleimide sensitive fusion protein (NSF) and
      alpha/beta soluble NSF attachment proteins (SNAPs) include the Pak-binding
      nucleotide exchange factor betaPIX.
AB  - N-ethylmaleimide sensitive fusion protein (NSF) is a chaperone that plays a
      crucial role in the fusion of vesicles with target membranes. NSF mediates the
      ATP-consuming dissociation of a core protein complex that assembles during
      vesicle fusion and it thereby recharges the fusion machinery to perform multiple
      rounds of fusion. The binding of NSF to the core complex is mediated by co
      chaperones named soluble NSF attachment proteins (SNAPs), for which three
      isoforms (alpha, beta and gamma) are known. Here, we sought to identify novel
      targets of the NSF-SNAP complex. A yeast two-hybrid screen using the brain
      specific betaSNAP isoform as bait revealed, as expected, NSF and several isoforms
      of the SNARE protein syntaxin as interactors. In addition, three isoforms of the
      reticulon protein family and two isoforms of BNIP3 interacted with betaSNAP. A
      yeast two-hybrid screen using NSF as bait identified Rab11-FIP3 and the Pak
      binding nucleotide exchange factor betaPIX as putative binding partners. betaPIX
      interacts with recombinant NSF in co-sedimentation assays and the two proteins
      may be co-immunoprecipitated. A leucine zipper (LZ) motif within the C-terminus
      of betaPIX mediates binding to NSF; however, this fragment of betaPIX does not
      exhibit dominant negative effects in a cellular assay. In summary, our results
      support the evolving view that NSF has numerous targets in addition to
      conventional SNARE complexes.

PMID- 16795054
TI  - Gene expression of human T lymphocytes cell cycle: experimental and bioinformatic
      analysis.
AB  - Human lymphocytes gene expression is monitored before and after PHA stimulation
      over 72 h, using DNA microarray technology. Results are then compared with our
      previous bioinformatics predictions, which identified six leader genes of highest
      importance in human T lymphocytes cell cycle. Experimental data are strikingly
      compatible with bioinformatic predictions of the specific role and interaction of
      PCNA, CDC2, and CCNA2 at all phases of the cell cycle and of CHEK1 in regulating
      DNA repair and preservation. It does not escape our notice that the conception
      and use of ad hoc arrays, based on a bioinformatics prediction which identifies
      the most important genes involved in a particular biological process, can really
      be an added value in cell biology and cancer research alternative to massive
      frequently misleading molecular genomics.

PMID- 16795055
TI  - Use of whole blood platelet lumi-aggregometry to optimize anti-platelet therapy
      in patients with chronic myeloproliferative disorders.
AB  - Twenty-seven patients with chronic myeloproliferative disorders and in vitro
      evidence of platelet hyperactivity on whole blood platelet lumi-aggregometry were
      commenced on anti-platelet therapy comprising aspirin, clopidogrel, and/or
      odorless garlic and the studies were repeated to assess the efficacy of the
      therapeutic agent(s). Only 8 patients showed clear evidence of anti-platelet
      effect while receiving the standard low-dose (100 mg/day) aspirin therapy.
      Thirteen patients required a higher dosage of aspirin and/or an additional anti
      platelet agent to achieve therapeutic adequacy. Lumi-aggregometry also proved
      useful to optimize therapy in the 6 patients who received clopidogrel or odorless
      garlic because of aspirin intolerance.

PMID- 16795056
TI  - New-onset and idiopathic thrombotic thrombocytopenic purpura: incidence,
      diagnostic validity, and potential risk factors.
AB  - OBJECTIVE: The aim of this study was to determine the incidence rate for new
      onset and idiopathic thrombotic thrombocytopenic purpura (TTP) among adults 20-64
      years old, the validity of diagnostic criteria, and potential risk factors for
      TTP. METHODS: This retrospective observational study analyzed automated
      administrative data from 11 geographically dispersed U.S. health plans. Cases of
      TTP were identified based on the presence of an inpatient hospital claim for TTP
      (ICD-9-CM 446.6) between 1/1/97 and 12/31/01 and confirmed by medical record
      review. Pharmacy and medical claims were used to evaluate outpatient drug
      exposure and comorbidities preceding hospitalization for TTP. Cases and the base
      population were screened so as to result in an incidence rate for idiopathic TTP.
      RESULTS: We confirmed new-onset and idiopathic TTP in 9 of 15 presumptive cases
      for an incidence density of 1.4 per million person-years (95% CI: 0.6-2.6). The
      rate increased to 1.8 per million person-years after projection and age
      standardization. The highest incidence rate of TTP was found in patients 50-64
      years old (2.8 per million person-years; 95% CI: 0.8-7.1). These 9 patients had
      no apparent risk factors for TTP based on claims and medical record data.
      CONCLUSIONS: In a general U.S. population, the incidence rate of confirmed new
      onset and idiopathic TTP was lower than previously reported, but appears to be on
      the rise. Our findings suggest that administrative claims data are useful for
      identifying outpatient drug exposures and comorbidities potentially associated
      with TTP.

PMID- 16795057
TI  - Coincidental outbreak of methicillin-resistant Staphylococcus aureus in a
      hematopoietic stem cell transplantation unit.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most
      common nosocomial pathogens among hospital-acquired infections, and
      immunocompromised patients are highly susceptive to infection. The molecular
      typing of isolated strains is a common method for tracing an outbreak of MRSA,
      but experience with this approach is still limited in the hematopoietic stem cell
      transplantation (HSCT) ward. METHODS: We experienced 6 cases of MRSA
      infection/colonization in our 26-bed HSCT ward during a 4-week period. This
      unusual outbreak strongly suggested that the same MRSA strain was involved
      despite strict isolation and aseptic patient care. Clarification of the
      transmission pattern was critical, and we applied pulsed-field gel
      electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) assays
      for evaluation. RESULTS AND CONCLUSION: In four of the six cases, the pattern of
      bands examined by PFGE and AFLP analyses supported the idea that direct person-to
      person transmission was very unlikely and the outbreak was coincidental. This
      experience highlights the clinical value of molecular typing methods for the
      clinical epidemiological assessment of MRSA outbreak.

PMID- 16795058
TI  - Pulmonary hypertension in thalassemia: association with platelet activation and
      hypercoagulable state.
AB  - The pathogenesis of pulmonary hypertension (PAH), a serious complication in
      thalassemia, is not well understood. Thromboembolism has been postulated as one
      of the causative factors; however, there are currently limited specific data on
      its role. To examine whether increased platelet activation and hypercoagulability
      are linked to PAH, 25 beta-thalassemia major and beta-thalassemia intermedia
      patients were evaluated with Doppler echocardiograms for estimation of pulmonary
      artery pressure and with laboratory assays for indications of a prothrombotic
      state. The association of clinical variables and abnormal coagulation assays with
      PAH was determined. PAH was identified in 17 (68%) patients; mean pulmonary
      artery systolic pressure was 39.8 +/- 5.4 mm Hg. PAH was significantly associated
      with prior splenectomy, older age, and evidence for chronic hemolysis, diagnosed
      in both transfused (n = 10) and nontransfused (n = 7) patients. Increased
      platelet activation, measured by P-selectin, was significantly associated with
      PAH (P = 0.001). Increased thrombin-antithrombin III level was more prevalent in
      the presence of PAH, but increased fibrinolysis or low protein C levels were not.
      This study underscores the role of platelet activation in the development of PAH
      and stresses its occurrence even among patients who are regularly transfused,
      especially those who are older and have had splenectomies.

PMID- 16795059
TI  - A family of severe congenital neutropenia with -199C to A substitution in ELA2
      promoter.

PMID- 16795060
TI  - AL amyloidosis associated with B-cell lymphoproliferative disorders: frequency
      and treatment outcomes.
AB  - AL amyloidosis, a systemic disorder characterized by widespread deposition of
      amyloid fibrils derived from monoclonal Ig light chains in organs and soft
      tissues, is typically caused by an underlying plasma cell dyscrasia. However,
      this disease can also be associated rarely with a B-cell lymphoproliferative
      disorder. In this report, we describe the presentation and clinical course of 16
      patients with this association. Although amyloid-related organ involvement in
      these patients was typical of AL amyloidosis, the patients in this series were on
      average older and more likely to be female than patients with disease associated
      with a plasma cell dyscrasia. They were also more likely to have multisystem
      involvement. Treatment decisions were based primarily on the dominent
      hematopathologic features of the associated lymphoproliferative disorder.
      However, high-dose melphalan and stem cell transplantation was the primary
      therapy in 5 patients, and each of these patients had prolonged survival, ranging
      from 36 to 102 months.

PMID- 16795061
TI  - Persistence of embryonic pattern of hepatocaval venous junction and patent ductus
      venosus in Budd-Chiari syndrome.
AB  - We report an autopsy study on a case of Budd-Chiari syndrome (BCS) in a 44-year
      old woman. Dissection showed that the outlets of the right hepatic vein (HV) and
      of the common trunk of the middle and left HVs appeared as two small depressed
      areas with narrow ostia. Histological examination showed recent thrombosis of the
      tributaries of the HVs and centrilobular congestion with necrosis of the hepatic
      parenchyma. The juxtacaval portions of the major HVs showed a cuneiform shape,
      because of marked dilation, with thread-like ostia, and multiple small outlets of
      minor hepatic veins were also present. The coexistence of patent ductus venosus
      may have prevented the development of the hepatocaval venous junction, with
      persistence of the embryonic pattern, composed of multiple small channels
      draining into the right hepatocardiac channel. The unusual hepatocaval venous
      junction may have predisposed to thrombosis of the HVs, causing BCS.

PMID- 16795062
TI  - Anatomical variations of the cords of brachial plexus and the median nerve.
AB  - The variations in formation, location, and courses of the cords of brachial
      plexus and the median nerve were studied in both axillae of 172 cadavers. The
      total prevalence of variation was 12.8% (CI, 7.6-17.4) and it was found in 13.2%
      (CI, 7.5-18) of male and in 10.7% (CI, -0.6-19.6) of female cadavers. These
      variations were divided into three groups. The first group was abnormal location
      of the cords, which was either posterolateral or anteromedial in relation to the
      axillary artery in 2.3% (CI, 0.1-4.5) cadavers. The lateral cord and the medial
      root of the median nerve had received communicating branches from the posterior
      cord in most of the cases of this group. The second group was absence of the
      posterior cord in 3.5% (CI, 0.7-6.1) of cadavers. The lateral and medial cords of
      this group were connected with the communicating branches, which had a course in
      front of the axillary artery. The third group was abnormal formation and course
      of the median nerve in 7% (CI, 3.1-10.6) of cadavers. In all cases of this group
      the medial root received communicating branch/branches either from the lateral or
      posterior cord. In eight (4.7%) cadavers, both roots of the median nerve were
      joined on medial side of the axillary artery to form a median nerve, which
      traveled medial to the artery. In four (2.3%) cadavers the roots of the median
      nerve did not join and both traveled separately anteromedial to the axillary and
      brachial arteries. This study indicates that all three cords and median nerve
      vary considerably in levels of origin, location and course in relation to the
      axillary artery and these variable cases were joined with the communicating
      branch/branches. The observed variations are of anatomical and clinical interest.
      These kinds of variations are more prone to injury in radical neck dissection and
      in other surgical operation of the axilla.

PMID- 16795063
TI  - Bloodstream infections in hospitalized adults with sickle cell disease: a
      retrospective analysis.
AB  - Bloodstream infections (BSI) are a common cause of morbidity and mortality in
      people with sickle cell disease (SCD). In children with SCD, BSI are most often
      caused by encapsulated organisms. There is a surprising paucity of medical
      literature that is focused on evaluating SCD adults with BSI. We reviewed the
      charts of adults with SCD and BSI who were admitted to our hospital between April
      1999 and August 2003. During this period a total of 1,692 hospital admissions for
      193 adults with SCD were identified and 28% of these patients had at least 1
      episode of positive blood cultures, with 69 episodes (17%) considered true BSI.
      Nosocomial BSI occurred in 34 episodes (49%). Among community BSI, in contrast to
      BSI in children with SCD, Streptococcus pneumoniae was rarely encountered. A high
      incidence of staphylococcal BSI in adults with SCD was noted. Twenty-eight
      percent of all BSI were caused by Staphylococcus aureus, and 15 of 22 isolates
      (68%) of these were methicillin-resistant. Gram-negative organisms, anaerobes,
      and yeast were found in 21 (27%), 3 (4%), and 4 isolates (5%) of BSI,
      respectively. Since over 80% of BSI were considered catheter-related, the higher
      incidence of gram-positive bacterial infections was likely due to the presence of
      indwelling central venous catheters. Empiric therapy for adults with SCD
      suspected of having BSI, especially in the presence of indwelling central venous
      catheters, should include antimicrobial therapy targeted at gram-positive
      bacteria (especially MRSA) and gram-negative bacteria. Also, if patients are
      critically ill, consideration should be made to include antifungal agents.
      Additional research into the adult SCD population appears necessary to further
      define this problem.

PMID- 16795064
TI  - Current status of lymph node-positive prostate cancer: Incidence and predictors
      of outcome.
AB  - In early surgical series, the incidence of positive lymph nodes in patients with
      prostate cancer was approximately 40%. In the modern era of screening and
      improved patient selection, the incidence is now <10%, although most series
      excluded patients with higher risk disease. The risk of having positive lymph
      nodes is influenced by disease stage, prostate-specific antigen level, and tumor
      grade and by the aggressiveness of lymph node dissection. Many of the same
      factors predict the outcome of these patients. Although the percentage of
      patients with positive lymph nodes has declined, there remain significant numbers
      of patients with lymph node-positive prostate cancer, and it remains a
      therapeutic dilemma.

PMID- 16795065
TI  - Emerging implications of nanotechnology on cancer diagnostics and therapeutics.
AB  - Nanotechnology is multidisciplinary field that involves the design and
      engineering of objects <500 nanometers (nm) in size. The National Cancer
      Institute has recognized that nanotechnology offers an extraordinary, paradigm
      changing opportunity to make significant advances in cancer diagnosis and
      treatment. In the last several decades, nanotechnology has been studied and
      developed primarily for use in novel drug-delivery systems (e.g. liposomes,
      gelatin nanoparticles, micelles). A recent explosion in engineering and
      technology has led to 1) the development of many new nanoscale platforms,
      including quantum dots, nanoshells, gold nanoparticles, paramagnetic
      nanoparticles, and carbon nanotubes, and 2) improvements in traditional, lipid
      based nanoscale platforms. The emerging implications of these platforms for
      advances in cancer diagnostics and therapeutics form the basis of this review. A
      widespread understanding of these new technologies is important, because they
      currently are being integrated into the clinical practice of oncology.

PMID- 16795066
TI  - Oncogenic T-antigen of JC virus is present frequently in human gastric cancers.
AB  - BACKGROUND: JC virus (JCV) is a polyomavirus that commonly infects humans and is
      the causative agent of progressive multifocal leukoencephalopathy in immune
      compromised patients. An association between JCV and human cancers long has been
      suspected, because this virus induces brain tumors in several animal models. The
      oncogenic potential of JCV is mediated by a transforming protein, the T-antigen
      (T-Ag), which is a multifunctional protein that transforms cells through
      interactions with various growth-regulatory genes, including p53 and pRb, and by
      stabilizing beta-catenin. Previously, the laboratory at the authors' institution
      demonstrated that JCV is present frequently in the human gastrointestinal tract
      and may play a role in colorectal carcinogenesis. However, to date, no studies
      have determined whether JCV sequences are present specifically in gastric
      cancers. The current study was designed to investigate whether JCV sequences and
      expression are found in human gastric cancers. METHODS: DNA was extracted from 23
      paraffin embedded and 14 frozen gastric cancer specimens. For the detection of
      JCV gene sequences, polymerase chain reaction amplifications were performed using
      gene-specific primers for T-Ag, VP-1 (a JCV capsid gene), and the viral
      regulatory region (or transcriptional control region). Immunohistochemical
      staining was performed with an anti-T-Ag monoclonal antibody to detect protein
      expression. RESULTS: Twenty-one of 37 gastric cancers (57%) harbored JCV T-Ag
      sequences, and 13 of 37 gastric cancers (30%) contained VP-1 sequences. T-Ag
      sequences also were found in adjacent nonneoplastic mucosa. In addition, JCV
      regulatory region sequences were present frequently in gastric cancers and
      adjacent nonneoplastic mucosa. T-Ag protein expression was found in 9 of 23
      gastric cancers (39%), whereas no expression was observed in any of the
      nonneoplastic tissues. CONCLUSIONS: To the authors' knowledge, this is the first
      demonstration of the presence of JCV T-Ag expression in human gastric cancers.
      These findings suggest a possible role for this polyomavirus in gastric
      carcinogenesis.

PMID- 16795067
TI  - Pilot trial of bone-targeted therapy with zoledronate, thalidomide, and
      interferon-gamma for metastatic renal cell carcinoma.
AB  - BACKGROUND: The purpose of the study was to evaluate the efficacy and safety of a
      bone-targeted regimen consisting of zoledronate, thalidomide, and interferon
      gamma in patients with renal cell carcinoma and bone metastases. METHODS:
      Eligible patients had radiographic evidence of bone metastasis. Impending
      pathologic fractures or spinal cord compressions must have been controlled by
      surgery or radiation therapy before enrollment. Zoledronate (4 mg) was given
      intravenously every 4 weeks, thalidomide (300 mg) was given orally once a day,
      and interferon-gamma (100 microg) was given subcutaneously once a week. Patients
      were evaluated for time to skeletal-related events, the appearance of
      calcification in osteolytic metastases, and levels of the bone
      formation/resorption markers. RESULTS.: Fifteen patients were treated between
      November 2002 and November 2003; 12 had previously undergone surgery, radiation,
      or embolization for their bone metastases; 11 had more than 3 sites of bone
      involvement; and 9 also had nonosseous metastases in the lung, liver, lymph node,
      pancreas, or adrenal gland. The median time to progression was 8.3 weeks (range,
      2.1-48 weeks). The median time to a skeletal-related event was 12.0 weeks (range,
      3.9-46.4 weeks). Two patients discontinued treatment because of adverse drug
      reactions (1 deep venous thrombosis and 1 myocardial infarction). Two patients
      experienced pain improvement and developed calcification in osseous metastases;
      these patients also showed favorable changes in bone marker levels. CONCLUSIONS:
      In this pilot study a bone-targeted regimen combining zoledronate, thalidomide,
      and interferon-gamma was well tolerated and might provide clinical benefit for a
      small subset of patients with renal cell carcinoma and bone metastases.

PMID- 16795068
TI  - Predictors of mortality after androgen-deprivation therapy in patients with
      rapidly rising prostate-specific antigen levels after local therapy for prostate
      cancer.
AB  - BACKGROUND: The authors identified biochemical and pathologic factors that were
      associated significantly with prostate cancer-specific mortality (PCSM) after
      androgen deprivation therapy (ADT) in men who had rapidly rising prostate
      specific antigen (PSA) levels after they received local treatment. METHODS: The
      study population consisted of 67 patients who had a PSA doubling time (DT) < or
      =6 months after radical prostatectomy (n = 50 patients) or external beam
      radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate
      Cox proportional hazards regression analysis was used to evaluate whether the
      interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation,
      time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were
      associated significantly with the time to PCSM 8 months after the initiation of
      ADT. RESULTS: : A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95%
      confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8
      (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with
      a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8%
      versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL,
      respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason
      score < or =7 versus > or =8, respectively. CONCLUSIONS: : Among men with a PSA
      DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or
      =8 cancer identified men who were at high risk for PCSM. These men would be ideal
      candidates for Phase III studies that evaluate the impact on survival of new
      systemic therapies for prostate cancer.

PMID- 16795069
TI  - Primary versus radiation-associated craniofacial osteosarcoma: Biologic and
      clinicopathologic comparisons.
AB  - BACKGROUND: Craniofacial osteosarcoma differs from long bone osteosarcoma in that
      patients are older, tumors are often low grade, and prognosis is more favorable.
      Although most are sporadic, some tumors occur in association with prior radiation
      therapy. The purpose of the current study was to compare clinicopathologic and
      prognostic features of primary and radiation-associated osteosarcoma. METHODS:
      The study group consisted of 15 primary and 6 radiation-associated osteosarcomas.
      Clinical and follow-up data were obtained in every case. Tissue microarrays were
      immunohistochemically stained for p53, pRB, Ki-67 (MIB-1), and ezrin. DNA was
      sequenced for TP53 mutations. RESULTS: All radiation-associated osteosarcomas
      were high grade and half were fibroblastic. In contrast, 47% of primary
      craniofacial osteosarcomas were high grade and only 1 was fibroblastic. All
      radiation-associated osteosarcomas recurred, half the patients died of disease, 2
      were alive with unresectable tumors, whereas only 1 was alive without disease. In
      contrast, 80% of patients with primary tumors were alive without disease, 33% had
      local recurrences, and 13% died of disease. Radiation-associated tumors
      overexpressed p53 more often (33% vs. 13%), more often had TP53 mutations (33%
      vs. 8%), had higher proliferative activity (67% vs. 0% showing >50% MIB-1
      staining), and expressed ezrin more frequently (83% vs. 40%) than primary tumors.
      Compared with a control group of 24 high- and 7 low-grade primary extremity
      osteosarcomas, radiation-associated tumors marked as the high-grade tumors.
      CONCLUSIONS: Craniofacial radiation-associated osteosarcomas are high-grade
      tumors that behave more aggressively than most primary craniofacial
      osteosarcomas. In addition, they demonstrate higher expression rates of adverse
      prognostic indicators, further highlighting the distinction.

PMID- 16795070
TI  - T-cell large granular lymphocyte leukemia: A report on the treatment of 29
      patients and a review of the literature.
AB  - BACKGROUND: To the authors' knowledge, there is no standard treatment for
      patients with T-cell large granular lymphocyte (LGL) leukemia. Available data are
      limited by patient numbers and coexisting pathologies. METHODS: The authors
      report on the use of immunosuppressants (cyclosporin A [CSA] and low-dose oral
      methotrexate [MTX] given continuously) and cytotoxic agents in the treatment of
      29 patients with T-cell LGL leukemia age over the past 20 years. RESULTS: The
      overall response rate (ORR) to MTX (n = 8 patients) was 85.7% (complete
      hematologic response [CHR] rate, 14.3%; partial response [PR] rate, 71.4%) with
      dose-dependent responses observed and safe usage of doses >10 mg/m2 per week in 2
      patients. The ORR to CSA (n = 23 patients) was 78.2% (CHR rate, 30.4%; PR rate,
      47.8%). The median time to response for both agents was 1 month. Toxicity,
      although it was minor in most patients and was more common in the CSA group,
      included second malignancies in 5 patients. An ORR of 67% (all CHR) was attained
      with pentostatin (n = 4 patients); recurrences developed after a median of 4.6
      years. Successful retreatment with pentostatin was possible but with increasing
      drug resistance. Cyclophosphamide induced CHR that lasted >7 years with bone
      marrow clearance in 1 of 4 patients. Alemtuzumab induced a PR in 1 patient who
      had refractory disease. CONCLUSIONS: Both MTX and CSA were efficacious in the
      treatment of T-cell LGL leukemia but generally required long-term maintenance
      therapy. The authors highlight the risks of second malignancies and persistence
      of bone marrow disease. Although MTX and CSA were effective as first-line
      therapy, alemtuzumab and pentostatin merit further investigation, particularly
      for refractory disease.

PMID- 16795073
TI  - Novel SPG6 mutation p.A100T in a Japanese family with autosomal dominant form of
      hereditary spastic paraplegia.
AB  - We describe a Japanese family in which inheritance of a novel mutation p.A100T in
      SPG6 resulted in an autosomal dominant form of hereditary spastic paraplegia
      (ADHSP). Clinical investigation showed a pure form of HSP. Our study demonstrates
      further allelic heterogeneity of SPG6.

PMID- 16795071
TI  - Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is
      frequent in hepatocellular carcinoma.
AB  - BACKGROUND: The secreted frizzled-related protein 1 gene (SFRP1) encodes a
      Wnt/beta-catenin signaling antagonist and frequently is inactivated by promoter
      methylation in many tumors. However, the role of SFRP1 in hepatocellular
      carcinoma (HCC) is not clear. Therefore, the authors investigated whether
      methylation of the SFRP1 promoter is common in HCC and whether it may influence
      SFRP1 expression. METHODS: Four HCC cell lines, 54 HCCs, 42 cirrhotic livers, 21
      livers with chronic hepatitis, and 15 normal control tissues were analyzed for 1)
      SFRP1 promoter methylation by using methylation-specific polymerase chain
      reaction analysis and bisulfite sequencing, 2) SFRP1 messenger RNA expression by
      using quantitative reverse transcriptase-polymerase chain reaction analysis, and
      3) loss of heterozygosity (LOH) by using microsatellite markers flanking the
      SFRP1 locus. HCC cells were treated with the demethylating agent 5-aza-2'
      deoxycytidine to determine whether it could restore SFRP1 expression. RESULTS:
      SFRP1 promoter methylation was observed in 75%, 48.2%, 21.4%, 14.3% and 0% in HCC
      cell lines, primary HCCs, cirrhotic livers, livers with chronic hepatitis, and
      normal control tissues, respectively. Methylation of the SFRP1 promoter region in
      HCCs increased significantly compared with control tissues. All samples with
      SFRP1 methylation showed down-regulation of SFRP1 expression. Demethylation
      treatment with 5-aza-2'-deoxycytidine in HCC cells restored SFRP1 expression.
      Moreover, LOH of markers D8S505 and D8S1722 was found in 25% and 27.6% of the
      informative samples, respectively. CONCLUSIONS: The current results suggested
      that promoter hypermethylation of SFRP1 is a common event in HCC and plays an
      important role in the regulation of SFRP1 expression. In addition to methylation
      mediated down-regulation of SFRP1, LOH also may play a role.

PMID- 16795074
TI  - Imaging, morphologic, and immunohistochemical correlation in gastrointestinal
      stromal tumors.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) recently have been
      distinguished morphologically, immunohistochemically, and genetically from other
      gastrointestinal-tract spindle cell neoplasms. The objective of this study was to
      correlate clinical and imaging findings with morphology and immunohistochemistry
      to diagnose GISTs and to differentiate them from other spindle cell lesions in
      the gastrointestinal tract. METHODS: The authors reviewed 9 patients who had
      tumors that were diagnosed as GIST by image-guided and endosonographic-guided
      fine-needle aspiration (FNA) with or without core biopsy (7 stomach tumors and 2
      intraabdominal tumors). The male:female ratio was 3:6, and the patients ranged in
      age from 38 years to 80 years. Onsite evaluation, preliminary cytologic
      evaluation, and immunohistochemistry were provided for 6 patients. Immunostains
      were performed, depending on sample size, on aspirates and/or core biopsies.
      RESULTS: On imaging studies, most tumors were smooth and homogenous, consistent
      with GIST. Tumors ranged in size from 1.8 cm to 22 cm. The largest neoplasm
      showed solid/cystic and necrotic components. Aspirates consisted of spindle cell,
      neoplastic proliferation arranged in fascicles that exhibited focal, nuclear
      palisading; indistinct, cytoplasmic borders; and no significant atypia or
      mitosis. Focal epithelioid changes or cytologic atypia and mitoses were observed
      in 2 tumors. Immunostains revealed tumor expression of CD117 and/or CD34 in 5 of
      6 tumors, expression of actin in 3 of 6 tumors, and expression of desmin in 1 of
      6 tumors. All tumors were diagnosed as GIST (or consistent with GIST for tumors
      that lacked immunochemical analysis). Five patients underwent surgical excision,
      and the GIST diagnosis was confirmed in 3 patients, whereas 1 tumor proved to be
      neurofibroma, and another tumor was leiomyoma. No surgical follow-up was
      available for the remaining 4 patients, who had imaging and morphologic findings
      consistent with GIST. CONCLUSIONS: In the setting of consistent clinical and
      radiologic findings, the combined use of cytomorphology and immunohistochemistry
      on FNA and/or core biopsy in most instances provides a reliable pathologic
      diagnosis of GIST. The need of sufficient material for performing ancillary
      studies and the usual impossibility of excluding malignancy are limitations of
      FNA cytology of GIST.

PMID- 16795075
TI  - Innate immune response to human bone marrow fibroblastic cell implantation in
      CB17 scid/beige mice.
AB  - Immunocompromised mouse models have been extensively used to assess human cell
      implantation for evaluation of cytotherapy, gene therapy and tissue engineering
      strategies, as these mice are deficient in T and B lymphoid cells. However, the
      innate immune response and its effect on human cell xenotransplantation in these
      mouse models are mainly unknown. The aim of this study is to characterise the
      myeloid populations in the spleen and blood of CB17 scid beige (CB17 sb) mice,
      and to study the inflammatory cell responses to xenogeneic implantation of
      enhanced green fluorescent protein (GFP)-labelled human bone marrow fibroblastic
      (HBMF) cells into CB17 sb mice. The results indicate that even though CB17 sb
      mice are deficient in B- and T-cells, they exhibit some increases in their
      monocyte (Mo), macrophage (Mphi) and neutrophil (Neu) populations. NK cell and
      eosinophil populations show no differences compared with wild-type Balb/C mice.
      An innate immune response, identified by CR3 (CD11b/CD18)-positive myeloid
      inflammatory cells and F4/80-positive macrophages, was evident in the tissues
      where HBMF cells were implanted. As a consequence, the majority of implanted HBMF
      cells were eliminated by 4 weeks after implantation. Interestingly, the
      mineralised matrix formed by osteogenic HBMF cells was also eroded by
      multinuclear Mphi-like giant cells. We conclude that CB17 sb mice retain active
      innate immune cells, which respond to HBMF cell xenotransplantation. This study
      highlights the importance of the innate immune cells in the anti-xenograft
      response and suggests that strategies to block the activities of these cells may
      ameliorate the progressive long-term elimination of xenotransplants.

PMID- 16795076
TI  - Determination of cardiac volumes and mass with FLASH and SSFP cine sequences at
      1.5 vs. 3 Tesla: a validation study.
AB  - PURPOSE: To compare cardiac cine MR imaging using steady state free precession
      (SSFP) and fast low angle shot (FLASH) techniques at 1.5 and 3 T, and to
      establish their variabilities and reproducibilities for cardiac volume and mass
      determination in volunteers. To assess the feasibility of SSFP imaging in
      patients at 3 T and to determine comparability to volume data acquired at 1.5 T.
      MATERIALS AND METHODS: Ten healthy volunteers underwent cardiac magnetic
      resonance imaging using SSFP and segmented gradient-echo FLASH, using both a 1.5
      and a 3 T MR system on the same day. Ten patients with impaired left ventricular
      (LV) function were also studied at both field strengths with SSFP. RESULTS: For
      both SSFP and FLASH, field strength had no effect on the quantification of LV and
      right ventricular (RV) volumes, mass, or function (P > or = 0.05 for field
      strength for all parameters). At both 1.5 and 3 T, SSFP yielded smaller LV mass
      (e.g., at 3 T 109 +/- 30 g vs. 142 +/- 37 g; P = 0.011) and larger LV volume
      (e.g., at 3 T end-diastolic volume 149 +/- 37 mL vs. 133 +/- 31 mL at 5 T; P =
      0.041) measurements than FLASH. In patients with reduced LV function, all volume
      and mass measurements were again similar for SSFP sequences at 1.5 vs. 3 T. In
      volunteers and patients, measurement variabilities for LV parameters were small
      for both field strength and sequences, ranging between 3.7% and 10.7% for mass.
      CONCLUSION: Compared to 1.5 T, cardiac cine MR imaging at 3 T, using either FLASH
      or SSFP sequences, is feasible and highly reproducible. Field strength does not
      have an influence on quantification of cardiac volume or mass, but the systematic
      overestimation of LV mass and underestimation of LV volume by FLASH compared to
      SSFP is present at both 1.5 and 3 T. Normal values for cardiac volumes and mass
      established at 1.5 T can be applied to scans obtained at 3 T.

PMID- 16795077
TI  - Osteogenic growth peptide effects on primary human osteoblast cultures: potential
      relevance for the treatment of glucocorticoid-induced osteoporosis.
AB  - The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide
      that has attracted considerable clinical interest as a bone anabolic agent and
      hematopoietic stimulator. In vivo studies on animals have demonstrated that the
      synthetic peptide OGP (10-14), reproducing the OGP C-terminal active portion [H
      Tyr-Gly-Phe-Gly-Gly-OH] increases bone formation, trabecular bone density and
      fracture healing. In vitro studies performed on cellular systems based on
      osteoblastic-like cell lines or mouse stromal cells, have demonstrated that OGP
      (10-14) increases osteoblast proliferation, alkaline phosphatase (ALKP) activity
      and matrix synthesis and mineralization. In view of a potential application of
      OGP (10-14) in clinical therapy, we have tested different concentrations of OGP
      (10-14) on primary human osteoblast (hOB) cultures. We have observed significant
      increases of hOB proliferation (+35%), ALKP activity (+60%), osteocalcin
      secretion (+50%), and mineralized nodules formation (+49%). Our experimental
      model based on mature hOBs was used to investigate if OGP (10-14) could prevent
      the effects on bone loss induced by sustained glucocorticoid (GC) treatments. A
      strong decrease in bone formation has been attributed to the effects of GCs on
      osteoblastogenesis and osteocyte apoptosis, while an increase in bone resorption
      was due to a transient osteoblastic stimulation, mediated by the OPG/RANKL/RANK
      system, of osteoclasts recruitment and activation. Moreover, GCs act on hOBs
      decreasing the release of osteoprotegerin (OPG) a regulator of the RANKL/RANK
      interaction. Here, we provide evidences that OGP (10-14) inhibits hOB apoptosis
      induced by an excess of dexamethasone (-48% of apoptotic cells). Furthermore, we
      show that OGP (10-14) can increase OPG secretion (+20%) and can restore the
      altered expression of OPG induced by GCs to physiological levels. Our results
      support the employment of OGP (10-14) in clinical trials addressed to the
      treatment of different bone remodeling alterations including the GC-induced
      osteoporosis.

PMID- 16795079
TI  - Effects of PPARgamma agonists on cell survival and focal adhesions in a Chinese
      thyroid carcinoma cell line.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists cause cell
      death in several types of cancer cells. The aim of this study was to examine the
      effects of two PPARgamma agonists, ciglitazone and 15-deoxy-delta(12,14)
      prostaglandin J2 (15dPGJ2), on the survival of thyroid carcinoma CGTH W-2 cells.
      Both ciglitazone and 15dPGJ2 decreased cell viability in a time- and dose
      dependent manner. Cell death was mainly due to apoptosis, with a minor
      contribution from necrosis. Increased levels of active caspase 3, cleaved poly
      (ADP-ribose) polymerase (PARP), and cytosolic cytochrome-c were noted. In
      addition, ciglitazone and 15dPGJ2 induced detachment of CGTH W-2 cells from the
      culture substratum. Both the protein levels and immunostaining signals of focal
      adhesion (FA) proteins, including vinculin, integrin beta1, focal adhesion kinase
      (FAK), and paxillin were decreased after PPARgamma agonist treatment. Meanwhile,
      reduced phosphorylation of FAK and paxillin was noted. Furthermore, PPARgamma
      agonists induced expression of protein tyrosine phosphatase-PEST (PTP-PEST), and
      of phosphatase and tensin homologue deleted on chromosome ten (PTEN). The
      upregulation of these phosphatases might contribute to the dephosphorylation of
      FAK and paxillin, since pre-treatment with orthovanadate prevented PPARgamma
      agonist-induced dephosphorylation of FAK and paxillin. Perturbation of CGTH W-2
      cells with anti-integrin beta1 antibodies induced FA disruption and apoptosis in
      the same cells, thus the downregulation of integrin beta1 by PPARgamma agonists
      resulted in FA disassembly and might induce apoptosis via anoikis. Our results
      suggested the presence of crosstalk between apoptosis and integrin-FA signaling.
      Moreover, upregulation and activation of PTEN was correlated with reduced
      phosphorylation of Akt, and this consequence disfavored cell survival. In
      conclusion, PPARgamma agonists induced apoptosis of thyroid carcinoma cells via
      the cytochrome-c caspase 3 and PTEN-Akt pathways, and induced necrosis via the
      PARP pathway.

PMID- 16795078
TI  - Cellular and molecular parameters of mesothelioma.
AB  - Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that
      line the body cavities, most commonly the pleural and peritoneal cavities.
      Although traditionally recognized as associated with occupational asbestos
      exposures, MMs can appear in individuals with no documented exposures to asbestos
      fibers, and emerging data suggest that genetic susceptibility and simian virus 40
      (SV40) infections also facilitate the development of MMs. Both asbestos exposure
      and transfection of human mesothelial cells with SV40 large and small antigens
      (Tag, tag) cause genetic modifications and cell signaling events, most notably
      the induction of cell survival pathways and activation of receptors, and other
      proteins that favor the growth and establishment of MMs as well as their
      resistance to chemotherapy. Recent advances in high-throughput technologies
      documenting gene and protein expression in patients and animal models of MMs can
      now be validated in human MM tissue arrays. These have revealed expression
      profiles that allow more accurate diagnosis and prognosis of MMs. More
      importantly, serum proteomics has revealed two new candidates (osteopontin and
      serum mesothelin-related protein or SMRP) potentially useful in screening
      individuals for MMs. These mechanistic approaches offer new hope for early
      detection and treatment of these devastating tumors.

PMID- 16795080
TI  - TGF-beta2 stimulates cranial suture closure through activation of the Erk-MAPK
      pathway.
AB  - Cranial sutures are important growth sites of the skull. During suture closure,
      the dura mater is one of the most important sources of various positive and
      negative regulatory signals. Previous results indicate that TGF-beta2 from dura
      mater strongly accelerates suture closure, however, its exact regulatory
      mechanism is still unclear. In this study, we confirmed that removal of dura
      mater in calvarial organ culture strongly accelerates sagittal suture closure and
      that this effect is further enhanced by TGF-beta2 treatment. TGF-beta2 stimulated
      cell proliferation in the MC3T3-E1 cell line. Similarly, it stimulated the
      proliferation of cells in the sutural space in calvarial organ culture.
      Furthermore, TGF-beta2-mediated enhanced cell proliferation and suture closure
      were almost completely inhibited by an Erk-MAPK blocker, PD98059. These results
      indicate that TGF-beta2-induced activation of Erk-MAPK is an important signaling
      component that stimulates cell proliferation to enrich osteoprogenitor cells,
      thereby promoting their differentiation into osteoblasts to achieve a rapid
      calvarial bone expansion.

PMID- 16795081
TI  - Targeted-HASTE imaging with automated device tracking for MR-guided needle
      interventions in closed-bore MR systems.
AB  - Percutaneous MR-guided interventions with needles require fast pulse sequences to
      image the needle trajectory with minimal susceptibility artifacts. Spin-echo
      pulse sequences are well suited for reducing artifact size; however, even with
      single-shot turbo spin-echo techniques, such as rapid acquisition with relaxation
      enhancement (RARE) or half-Fourier acquisition single-shot turbo spin-echo
      (HASTE), fast imaging remains challenging. In this work we present a HASTE pulse
      sequence that is combined with inner-volume excitation to reduce the scan time
      and limit the imaging field of view (FOV) to a small strip close to the needle
      trajectory (targeted-HASTE). To compensate for signal saturation from fast
      repeated acquisitions, a magnetization restore pulse (driven equilibrium Fourier
      transform (DEFT)) is used. The sequence is combined with dedicated active marker
      coils to measure the position and orientation of the needle so that the targeted
      HASTE image slice is automatically repositioned. In an animal experiment the
      coils were attached to an MR-compatible robotic assistance system for MR-guided
      interventions. Needle insertion and infusion via the needle could be visualized
      with a temporal resolution of 1 s, and the needle tip could be localized even in
      the presence of a stainless steel mandrel.

PMID- 16795082
TI  - MR assessment of changes of tumor in response to hyperbaric oxygen treatment.
AB  - Enhancement of image intensity, using the T1-weighted spoiled gradient-echo
      (SPGR) sequence, was measured in SCC tumor implanted in the flank of C3H mice
      while they were subjected to several types of oxygenation challenges inside a
      hyperbaric chamber designed and constructed to fit in an MRI resonator. The
      central portions of the tumor gave a positive enhancement, while the periphery
      showed signal reduction during both normobaric (NBO) and hyperbaric (HBO) oxygen
      challenges. In the contralateral normal leg, nearly 70% of the region showed a
      decrease in intensity, and the rest showed a positive enhancement. The positive
      signal enhancement was markedly greater under HBO compared to NBO. Calculated R1,
      R2, and M0 maps from multivariate fitting of images acquired by a multislice
      multiecho (MSME) sequence with variable TR before, during, and after HBO
      treatment confirm that the source of SPGR signal enhancement in the tumor is
      associated with shortening of T1.

PMID- 16795083
TI  - Discrimination of errors from neuronal activity in functional MRI of the human
      spinal cord by means of general linear model analysis.
AB  - Functional MRI (fMRI) of the spinal cord has been demonstrated to provide
      reliable and sensitive maps of neuronal activity, particularly when combined
      across several experiments. Individual experiments reveal neuronal activity as
      well as errors. The dominant source of errors is hypothesized to be physiological
      motion, including cardiac and respiratory motion, flow of blood and cerebrospinal
      fluid (CSF), and motion of the spinal cord within the spinal canal. All of the
      hypothesized sources of error are therefore related to cardiac and respiratory
      motion, which can be recorded during an fMRI experiment. Analyses were carried
      out with a general linear model (GLM) with peripheral pulse and respiration
      recordings used as models of errors. The results demonstrate that the sensitivity
      of spinal fMRI is improved and errors are reduced when peripheral pulse traces
      are used in the GLM, but no improvement was detected with the inclusion of
      respiratory traces.

PMID- 16795085
TI  - Exposure to wood smoke, HPV infection, and genetic susceptibility for cervical
      neoplasia among women in Colombia.
AB  - Cervical cancer is the second leading cause of death from cancer among women in
      Colombia (16/100,000). Infection with high-risk human papillomavirus (HPV) plays
      a major role in the etiology of high-grade squamous intraepithelial lesions
      (HSILs). Exposure to chemical agents may be a cofactor for tumor induction, and
      individual genetic differences in the metabolism of these chemical agents may
      affect the susceptibility of individuals towards the development of HSIL. In this
      case-control study, a total of 91 cases with HSIL and 92 healthy controls,
      frequency-matched by age and place of origin, were recruited, and their
      frequencies of CYP2E1, GSTM1, and GSTT1 polymorphism were determined. We then
      evaluated the association of these polymorphisms, by themselves and in
      combination with wood smoke exposure and HPV-infection status, with the risk of
      HSIL. The results indicate that GSTM1 and GSTT1 polymorphism were not associated
      with HSIL, although a small increase in risk was observed for individuals who
      were GSTT1 null (OR = 1.4, 95% CI = 0.57-3.44). Contrary to other investigations,
      the c2/c2 variant of the CYP2E1 gene was associated with a significant increase
      in risk after adjusting for wood smoke exposure (OR = 6.3, 95% CI = 1.10-36.38)
      or wood smoke exposure and HPV-infection status (OR = 10.7, 95% CI = 1.76-65.58).
      Wood smoke exposure also increased the risk of HSIL among CYP2E1 c2/c2 HPV
      positive women (OR = 3.3, CI = 0.50-22.50); however, the increase did not achieve
      statistical significance. Our study provides tantalizing evidence that genetic
      differences in the metabolism of wood smoke carcinogens, particularly metabolism
      by CYP2E1, may confer susceptibility for HSIL development. Further investigations
      with larger populations will be needed to confirm this association, which may
      provide important information for improving cervical cancer prevention programs.

PMID- 16795086
TI  - Evaluation of micronucleus frequencies and DNA damage in glass workers exposed to
      arsenic.
AB  - Arsenic (As) is a known human carcinogen; however, very little is known about the
      health consequences of occupational exposure to As. In the present study, we
      assessed the genotoxic damage in the blood cells and in the buccal cells of south
      Indian glass factory workers who are occupationally exposed to As. The As content
      in the whole blood of 200 workers and 165 controls was evaluated with inductively
      coupled plasma mass spectrometry. Blood leukocytes from the subjects were
      monitored for the level of DNA damage using the Comet assay (mean comet tail
      length); buccal cells were used to determine the frequency of micronuclei (MN).
      The mean As concentration was significantly higher in the workers (56.76
      microg/L) than in the controls (11.74 microg/L) (P < 0.001). The workers also had
      increased frequencies of MN in the buccal cells and increased levels of DNA
      damage in leukocytes compared to the controls (P < 0.001). There were significant
      correlations between the genotoxicity endpoints that were evaluated and blood As
      concentration, smoking, age, and the duration of working in the factory. Also, a
      significant correlation was observed between the frequency of MN and comet tail
      length for the worker samples. Our findings indicate that chronic occupational
      exposure to As is genotoxic and that the Comet assay and micronucleus test are
      useful assays for evaluating genotoxicity in humans occupationally exposed to As.

PMID- 16795087
TI  - Influence of the SCGE protocol on the amount of basal DNA damage detected in the
      Mediterranean mussel, Mytilus galloprovincialis.
AB  - Genotoxicity studies using the single cell gel electrophoresis (SCGE) assay
      indicate that basal levels of DNA strand breaks (SBs) in marine invertebrates are
      higher and more variable than those in marine vertebrates. This elevated level of
      DNA damage was attributed to a large number of alkali-labile sites, which are
      characteristic of the tightly-packaged DNA in invertebrate cells. To investigate
      if altering the SCGE protocol can artificially modulate high levels of SBs, SCGE
      experiments were performed on haemocytes from the Mediterranean mussel (Mytilus
      galloprovincialis) using proteinase K (PK) digestion in combination with assay
      buffers containing various concentrations of EDTA. In addition, the effects of
      Trolox (soluble antioxidant) and aurintricarboxylic acid (ATA; inhibitor of
      Ca(2+)/Mg(2+)-dependent nucleases) also were tested. The levels of SBs in M.
      galloprovincialis cells were compared with SBs in cells from a terrestrial
      mollusk (the snail Helix aspersa), and a teleost fish (the seabass Dicentrarchus
      labrax). The integrity of M. galloprovincialis DNA isolated with phenol
      extractions using EDTA, Trolox, and ATA was further assayed by gel
      electrophoresis. High SBs in mussel cells were reduced by combining EDTA with PK
      digestion, or using Trolox or ATA during cell processing for the SCGE assay.
      Snails and seabass had lower levels of SBs in the SCGE assay, and the levels were
      not affected by the protocol modifications. Adding EDTA, Trolox, or ATA to phenol
      extractions of M. galloprovincialis genomic DNA also reduced the extent of DNA
      fragmentation. These results suggest that the internal fluids of M.
      galloprovincialis may increase the basal levels of DNA SBs through oxidative
      and/or enzyme-mediated pathways. M. galloprovincialis is used extensively as a
      sentinel species for assessing the genotoxic hazard of marine pollutants. Our
      data suggest that the SCGE protocol should be carefully considered when assessing
      DNA damage in these species.

PMID- 16795088
TI  - DNA damage and acute toxicity caused by the urban air pollutant 3
      nitrobenzanthrone in rats: characterization of DNA adducts in eight different
      tissues and organs with synthesized standards.
AB  - 3-Nitrobenzanthrone (3-NBA) is an urban air pollutant and rat lung carcinogen
      that is among the most potent mutagens yet tested in the Salmonella reversion
      assay. In the present study, 1 mg 3-NBA was administered orally to female F344
      rats and DNA adduct formation was examined in liver, lung, kidney and five
      sections of the gastrointestinal (GI) tract at 6 hr, and 1, 2, 3, 5, and 10 days
      after administration. The DNA adduct patterns, analyzed by (32)P-postlabelling
      followed by HPLC separation, were similar in all tissues and organs. Five of the
      adduct peaks cochromatographed with synthesized DNA adduct standards. Three of
      these unequivocally determined standards, dGp-C8-N-ABA, dGp-N2-C2-ABA, and dAp-N6
      C2-ABA, were of the nonacetylated type, suggesting that at least part of the
      pathway for activation of 3-NBA proceeds through O-acetylation of the
      hydroxylamine intermediate. The two other DNA adduct standards, dGp-C8-C2-N-Ac
      ABA, and dGp-N2-C2-N-Ac-ABA, were of the acetylated type, but there was some
      ambiguity in the characterization of these DNA adducts, since they varied
      inconsistently between samples and they also aligned with peaks found in
      controls. At 6 hr after treatment, the level of DNA adducts was highest in
      glandular stomach (relative adduct labeling (RAL), approximately 70 adducts/10(8)
      normal nucleotides (NN)); adduct levels in this organ decreased at 24 hr, but
      increased afterwards. DNA adduct levels in the majority of organs were
      characterized by an early increase (from 6 hr to 3 days), which was followed by a
      decrease at 5 days and a maximum level 10 days after administration (RAL
      approximately 120 adducts/10(8) NN for the lung, kidney and glandular stomach,
      approximately 80 adducts/10(8) NN for the forestomach and ceacum, and
      approximately 40 adducts/10(8) NN for the liver, small intestine, and colon).
      This pattern was consistent with pathological observations during autopsy showing
      high levels of tissue damage in the GI tract; the tissue damage included
      hemorrhages, loss of villous surface structure in the small intestine, as well as
      intestine fragility and oedema of the adipose tissue around the GI-tract. Tissue
      damage decreased and DNA adduct levels increased at 10 days after administration.
      These observations suggest that 3-NBA not only exerts acute toxic effects, but
      that the bioavailability is affected by storage in tissues and later becomes
      available, resulting in the increased DNA adduct levels at the later time points
      of collection.

PMID- 16795089
TI  - Urinary concentrations of bisphenol A in relation to biomarkers of sensitivity
      and effect and endocrine-related health effects.
AB  - The impact of endocrine-disrupting chemicals (EDCs) on human health is not yet
      clear because of difficulties in ascertaining their biological effects. In the
      present study, we evaluated exposure to the EDC, bisphenol A (BPA), in 172
      Koreans in relation to biomarkers of susceptibility and effect. The subjects
      completed questionnaires, which documented occupation, education, lifestyle
      factors, potential sources of BPA-exposure, and the occurrence of self-diagnosed
      endocrine disorders. None of the subjects were occupationally exposed to BPA;
      however, urinary levels of conjugated BPA, determined by HPLC/FD, ranged from
      0.03-62.4 microg/l (median, 7.86). The frequencies of potential susceptibility
      biomarkers, the UGT1A6-Arg184Ser and the SULT1A1-Arg213His polymorphisms, were
      not associated with urinary BPA levels, either as single genes or in combination.
      Indirect effects of BPA exposure on the susceptibility to mutagens were evaluated
      by comparing urinary BPA concentrations with MNNG-induced sister-chromatid
      exchange (SCE) in lymphocytes cultured from the subjects. BPA exposure showed
      marginal or significant associations with theSCEs induced by the low doses of
      MNNG (0-0.4 mM). However, there was no overall association between urinary BPA
      levels and MNNG-induced frequency at doses ranging from 0.2-0.6 mM. Finally, we
      did not detect an association between urinary BPA concentration and endocrine
      related disorders. Even though we were unable to find a strong association
      between BPA exposure and a biological response, possibly because of the limited
      number of subjects, we observed that most of the subjects were exposed to BPA.
      Therefore, continuous biological monitoring of BPA is a prudent measure to
      prevent possible BPA-related health risks.

PMID- 16795090
TI  - Intracranial aneurysm stenting: follow-up with MR angiography.
AB  - Intracranial stenting is increasingly being used to treat intracranial aneurysms
      and stenoses. We wanted to assess the utility of magnetic resonance angiography
      (MRA) in the follow-up of patients treated with various types of intracranial
      stents and to assess the utility of performing gadolinium-enhanced MRA. A total
      of 19 patients having undergone intracranial stenting for aneurysms were imaged
      by MRI at 1.5T. A total of 20 stents were placed in 19 patients. In addition to
      conventional T2- and diffusion-weighted MRI, 3D time-of-flight MRA was performed
      before and after contrast administration. In the case of metallic INX stents (N =
      7), there was a signal drop at the level of the vessel. which did not allow to
      evaluating the parent vessel, whereas this was visible in Nitinol stents (N = 8).
      Additionally a stent with a wire had a small artifact (N = 3). Contrast
      administration also improved vessel lumen visualization. In the case of Nitinol
      stents, MRA can be used to reliably demonstrate the vessel lumen after
      intracranial stenting. The use of postcontrast 3D time-of-flight imaging helps
      improve the intraluminal definition.

PMID- 16795091
TI  - Estimate of vascular permeability and cerebral blood volume using Gd-DTPA
      contrast enhancement and dynamic T2*-weighted MRI.
AB  - PURPOSE: To develop a numerical approach for estimation of vascular permeability
      from dynamic T2*-weighted imaging, a technique routinely used to measure cerebral
      blood volume (CBV) and flow in gliomas. MATERIALS AND METHODS: This study
      describes a process for estimating both the gadolinium diethylenetriamine
      pentaacetic acid (Gd-DTPA) transvascular transfer constant and CBV from dynamic
      T2*-weighted images. The algorithm was applied to data from the brains of 12
      patients with grade IV gliomas. The stability of the method was assessed.
      Estimates of CBV by this technique were compared to those of the conventional
      method. RESULTS: The algorithm was found to be insensitive to noise and to
      generate stable voxel-by-voxel estimates of permeability and CBV. CONCLUSION:
      Using a single imaging acquisition, the three most important vascular properties,
      CBV, cerebral blood flow (CBF), and permeability, can be estimated. This approach
      may have potential in clinical evaluation of patients with brain tumor or acute
      ischemic stroke.

PMID- 16795093
TI  - From single molecules to nanoscopically structured functional materials: Au
      nanocrystal growth on TiO2 nanowires controlled by surface-bound silicatein.

PMID- 16795092
TI  - Proton MR spectroscopy of the femoral head--evaluation of patients at risk for
      avascular necrosis.
AB  - PURPOSE: To detect alteration of the fatty component by measuring the in vivo
      lipid and water content of normal-looking femoral heads of patients with and
      without risk for avascular necrosis (AVN) by using proton MR spectroscopy (MRS).
      MATERIALS AND METHODS: Marrow composition was measured by proton MRS (TR/TE =
      5000/20 msec) in a sample volume placed in the epiphysis of the intact femoral
      heads of patients with unilateral osteonecrosis of the hip (group 1, N = 61, then
      excluding the post-traumatic or steroid user, final N = 45) and age-matched
      controls (group 2, N = 49). Three response variables were derived from MRS: the
      lipid linewidth (LW), water LW, and lipid/water ratio. RESULTS: Of the three
      variables, the lipid and water LWs differed significantly between groups (P <
      0.001 and P = 0.05, respectively; t-test). The lipid/water ratio had borderline
      significance (P = 0.06). The three variables differed significantly between
      groups when multivariate regression (P < 0.0001) was analyzed; and age and sex
      had no significant effect on the three dependent variables. CONCLUSION: Proton
      MRS can depict alteration in the lipid and water composition of normal-looking
      femoral heads with and without AVN on the contralateral hip. Proton MRS may be a
      potential tool for investigating of the femoral head component in vivo and
      predicting the risk for development of AVN.

PMID- 16795094
TI  - Highly efficient aerobic oxidation of alcohols using a recoverable catalyst: the
      role of mesoporous channels of SBA-15 in stabilizing palladium nanoparticles.

PMID- 16795095
TI  - Overcoming the insolubility of molybdenum disulfide nanoparticles through a high
      degree of sidewall functionalization using polymeric chelating ligands.

PMID- 16795096
TI  - Reactions of [ZnR2(L)] complexes with dioxygen: a new look at an old problem.

PMID- 16795097
TI  - Experimental evidence for linear metal-azido coordination: the binary group 5
      azides [Nb(N3)5], [Ta(N3)5], [Nb(N3)6]-, and [Ta(N3)6]-, and 1:1 acetonitrile
      adducts [Nb(N3)5(CH3CN)] and [Ta(N3)5(CH3CN)].

PMID- 16795098
TI  - Chiral Bronsted acid catalyzed enantioselective aza-Diels-Alder reaction of
      Brassard's diene with imines.

PMID- 16795099
TI  - Anisotropic decoration of gold nanoparticles onto specific crystal faces of
      organic single crystals.

PMID- 16795100
TI  - Single-step conversion of dimethyl terephthalate into cyclohexanedimethanol with
      Ru5PtSn, a trimetallic nanoparticle catalyst.

PMID- 16795101
TI  - Formation of monodisperse (WO3)3 clusters on TiO2(110).

PMID- 16795102
TI  - Can C3-symmetric receptors differentiate enantiomers?

PMID- 16795103
TI  - The first crystal structure of tyrosinase: all questions answered?

PMID- 16795105
TI  - Umpolung reactivity of alkenyl Fischer carbene complexes, copper enolates, and
      electrophiles.

PMID- 16795104
TI  - Asymmetric total synthesis of (-)-merrilactone A: use of a bulky protecting group
      as long-range stereocontrolling element.

PMID- 16795106
TI  - Synthesis and antiviral evaluation of novel cyclopropyl nucleosides, phosphonate
      nucleosides and phosphonic acid nucleosides.
AB  - Novel phenyl-branched cyclopropyl nucleosides, phosphonates, and phosphonic acid
      analogues were designed and synthesized as potential antiviral agents. Coupling
      of the mesylate 10 with natural bases (U, T, C, A) and desilylation/hydrolysis
      afforded a series of novel cyclopropyl nucleosides 15-18. Phosphonate and
      phosphonic acid nucleosides 22-29 were also readily synthesized from the mesylate
      21. The synthesized compounds were evaluated for their antiviral activity against
      various viruses such as HIV-1, HSV-1, HSV-2, and HCMV.

PMID- 16795107
TI  - Synthesis and molluscicidal activity of new cinnoline and pyrano [2,3-c]pyrazole
      derivatives.
AB  - 2-(3-Hydroxy-5,5-dimethylcyclohexylidene)malononitrile 5 undergoes an azo
      coupling reaction with aryldiazonium salts to afford 3-amino-2-aryl-6,6-dimethyl
      8-oxo-2,6,7,8-tetrahydrocinnoline-4-carbonitriles 7. Upon reflux in acetic acid,
      these compounds were acetylated to give the cinnoline derivatives 9. The
      pyrazolones 10a, b react with 3-furfurylidene- and 3-thienylidene-malononitrile
      derivatives 11a, b to afford the pyrano[2,3-c]pyrazole derivatives 13a-d. These
      newly synthesized compounds show generally a moderate molluscicidal activity to
      Biomphalaria alexandrina snails.

PMID- 16795108
TI  - Active site comparison of CoII blue and green nitrite reductases.
AB  - Copper-containing nitrite reductases (NiRs) possess type 1 (T1) and type 2 (T2)
      copper sites and can be either green or blue in color owing to differences at
      their T1 centers. The active sites of a green and a blue NiR were studied by
      utilizing their T1CuI/T2CoII and T1CoII/T2CoII-substituted forms. The UV/Vis
      spectra of these derivatives highlight the similarity of the T2 centers in these
      enzymes and that T1 site differences are also present in the CoII forms. The
      paramagnetic NMR spectra of T1CuI/T2CoII enzymes allow hyperfine shifted
      resonances from the three T2 His ligands to be assigned: these exhibit remarkably
      similar positions in the spectra of both NiRs, emphasizing the homology of the T2
      centers. The addition of nitrite results in subtle alterations in the
      paramagnetic NMR spectra of the T1CuI/T2CoII forms at pH<7, which indicate a
      geometry change upon the binding of substrate. Shifted resonances from all of the
      T1 site ligands have been assigned and the CoII--N(His) interactions are alike,
      whereas the CbetaH proton resonances of the Cys ligand exhibit subtle chemical
      shift differences in the blue and green NiRs. The strength of the axial CoII-
      S(Met) interaction is similar in the two NiRs studied, but the altered
      conformation of the side chain of this ligand results in a dramatically different
      chemical shift pattern for the CgammaH protons. This indicates an alteration in
      the bonding of the axial ligand in these derivatives, which could be influential
      in the CuII proteins.

PMID- 16795109
TI  - Synthesis of extended triphenylenes by palladium-catalyzed [2+2+2] cycloaddition
      of triphenylynes.
AB  - The synthesis of ortho-(trimethylsilyl)triphenylenyl triflates 7 is described.
      Fluoride-induced decomposition of these triflates leads to the generation of
      didehydrotriphenylenes (triphenylynes) 6. These arynes undergo [4+2]
      cycloadditions with dienes to afford the corresponding Diels-Alder adducts or
      palladium-catalyzed formal [2+2+2] cycloadditions to afford extended
      triphenylenes.

PMID- 16795110
TI  - Chiral poly(ureidophthalimide) foldamers in water.
AB  - Poly(ureidophthalimide)s decorated with hydrophilic side chains, that ensure
      solubility in aqueous media, have been synthesized and characterized by UV/Vis
      and circular dichroism (CD) spectroscopy. Temperature and concentration dependent
      CD measurements in water have revealed an almost temperature and concentration
      independent Cotton effect, indicative for a strong intramolecular organization.
      Similar studies in THF demonstrate the dynamic nature of the secondary
      architecture, a characteristic of foldamers. In addition, the bisignated Cotton
      effect in water is opposite in sign to that in THF, suggestive for a solvent
      dependent preference for one helical handedness. Mixing experiments prove the
      dominance of water in determining the handedness of the helical architecture. The
      solvent allows for control over the helical architecture and thus governs the
      supramolecular synthesis.

PMID- 16795111
TI  - C3 symmetry: molecular design inspired by nature.

PMID- 16795112
TI  - Ligands for molecular imaging: the synthesis of bis(thiosemicarbazone) ligands.
AB  - Bis(thiosemicarbazones) have been of interest to chemists for over fifty years;
      they display antitumour, antibiotic and antiviral properties. Recently it has
      become apparent that they may also provide a convenient way of labelling
      biologically active molecules by using metallic radionuclides and/or
      fluorescence. Although apparently simple, the synthesis of bis(thiosemicarbazone)
      ligands can be problematic. This article provides a summary of the published
      literature, based on the synthetic strategies used and indicates some of the
      difficulties that may arise.

PMID- 16795113
TI  - Bone marrow and tumour stroma: an intimate relationship.
AB  - In recent years the bone marrow has become recognized as a potential source of
      cells for non-haematopoietic wound healing, in some instances demonstrating
      surprising plasticity in providing new epithelial cells. On the other hand, the
      contribution of bone marrow derived cells to fibrosis and blood vessel formation
      is more widely acknowledged. Tumour stroma has a vital role to play in
      determining cancer growth and spread, and there is a growing realization that the
      bone marrow has a significant input into this desmoplastic response. This review
      focuses on the contribution of bone marrow cells to tumour stroma, highlighting
      the bone marrow as a potential new portal through which to direct anti-tumour
      therapies.

PMID- 16795114
TI  - Screening the fetal heart.

PMID- 16795116
TI  - Synthetic ligands able to interact with the p53 tetramerization domain. Towards
      understanding a protein surface recognition event.
AB  - The applied interaction of synthetic molecules with defined regions of protein
      surfaces is an emerging strategy for the modulation of protein activity and/or
      stability. In spite of recent advances, the design of these molecules is not
      trivial. Among the most challenging aspects in designing these compounds is that
      they must compete with water molecules for interaction with polar patches of
      protein surfaces. Herein is reported the preparation of an arginine-rich peptide
      that interacts in aqueous solution with a very hydrophilic patch at the surface
      of the tetramerization domain of the tumor suppressor protein p53. The
      interaction has been studied by several complementary techniques. By using this
      peptide as a template, a library of peptides has been prepared and evaluated in
      order to examine the different factors that contribute to the recognition event.
      The conclusions extracted from this work could be useful for the design of
      ligands directed at highly hydrophilic protein surface patches.

PMID- 16795115
TI  - Factors affecting technical success of fetal aortic valve dilation.
AB  - OBJECTIVE: We have reported previously that valve dilation enhances growth of
      cardiac structures and may prevent hypoplastic left heart syndrome (HLHS) in
      fetuses with critical aortic stenosis. We aimed to investigate maternal/fetal
      factors which may affect the technical success of fetal valvuloplasty, and to
      describe perinatal complications of the procedure. METHODS: This was a
      descriptive series of 22 fetuses diagnosed with critical aortic stenosis
      developing into HLHS which underwent intervention by valvuloplasty. Initially
      this was attempted using a percutaneous approach; reassessment after our first
      five attempts, only one of which was successful, led to the introduction of the
      option of laparotomy. Technical success was defined as balloon inflation across
      the aortic annulus and a broader jet through the aortic valve as assessed by
      Doppler. Data collected included body mass index, demographic variables,
      ultrasound findings and postprocedure interventions. RESULTS: Technical success
      increased significantly if maternal laparotomy was an option (83.3% vs. 20.0%, P
      = 0.017). Laparotomy was performed in 66.6% (12/18) of cases. There was a
      learning curve that showed an increase in success rate and decrease in need for
      laparotomy over the 3-year study period. Neither the need for laparotomy nor the
      chances of technical success were predictable by gestational age, body mass index
      or placental location. Tocolysis was limited to perioperative prophylaxis; one
      woman experienced wound infection and fluid overload. Postoperatively, three
      fetuses died and two delivered prematurely, 2 and 7 weeks after intervention.
      CONCLUSION: Fetal aortic valvuloplasty can be performed with technical success,
      with low fetal loss rate and few maternal complications. While the need for
      laparotomy cannot be predicted, having it available as an option improves the
      technical success rate.

PMID- 16795118
TI  - E and Z alpha-C-galactosylceramides by Julia-Lythgoe-Kocienski chemistry: a test
      of the receptor-binding model for glycolipid immunostimulants.

PMID- 16795119
TI  - Thermostable glycosynthases and thioglycoligases derived from Thermotoga maritima
      beta-glucuronidase.

PMID- 16795122
TI  - Scientifically and ethically responsible innovation and research in ultrasound in
      obstetrics and gynecology.

PMID- 16795121
TI  - Inactivation of gilGT, encoding a C-glycosyltransferase, and gilOIII, encoding a
      P450 enzyme, allows the details of the late biosynthetic pathway to gilvocarcin V
      to be delineated.
AB  - Resequencing of the gilGT gene, which encodes a putative glycosyltransferase (GT)
      that is 495 amino acids (aa) long, from the Streptomyces griseoflavus Go3592
      gilvocarcin V (GV) gene cluster, revealed that the previously reported gilGT
      indeed contains two genes. These are the larger gilGT, which encodes the C
      glycosyltransferase GilGT (379 aa), and the smaller gilV gene, which encodes an
      enzyme of unknown function (116 aa). The gene gilV is located immediately
      upstream of gilGT in the GV gene cluster. In-frame deletion of gilGT created a
      mutant that accumulated defucogilvocarcin E (defuco-GE). The result proves the
      function of GilGT as a C-glycosyltransferase. Deletion of gilOIII, which is
      located immediately downstream of gilGT, led to a mutant that accumulated
      gilvocarcin E (GE). This confirms that the corresponding P450 enzyme, GilOIII, is
      involved in the vinyl-group formation of GV. Cross-feeding experiments in which
      GE, defuco-GE, and defucogilvocarcin V (defuco-GV) were fed to an early blocked
      mutant of the GV biosynthetic pathway, showed that neither GE nor any of the
      defuco- compounds was an intermediate of the pathway.

PMID- 16795123
TI  - Changes in pulmonary venous Doppler parameters in fetal cardiac defects.
AB  - OBJECTIVES: Recent observations in pediatric cardiological studies have prompted
      discussion on the possible role of intrauterine pulmonary venous changes in
      neonatal and postoperative outcome of infants with congenital heart defects. This
      study analyzes changes of Doppler blood flow velocity waveforms in the pulmonary
      veins of fetuses with different cardiac defects. METHODS: Eighty fetuses (mean
      gestational age, 27 weeks) with prenatally diagnosed cardiac defects were
      classified into one of five groups: obstructed left atrium, other left
      ventricular outflow tract obstruction, right ventricular outflow tract
      obstruction, miscellaneous cardiac defects and total anomalous pulmonary venous
      drainage. Doppler examination of the pulmonary veins was performed and the time
      velocity integral (TVI), end-diastolic (A) velocity, and pulsatility index for
      veins (PIV) were compared with reference ranges. RESULTS: Fetuses with
      infradiaphragmatic total anomalous pulmonary venous drainage showed a continuous
      Doppler flow pattern instead of the typical pulsatile waveform pattern. In
      fetuses with obstructed left atrium and restrictive foramen ovale, a reversed A
      velocity and increased PIV were found. In five of the eight fetuses with left
      outflow tract obstruction but patent mitral valve, PIV was increased. In the
      other groups there were no obvious changes in Doppler parameters. CONCLUSIONS: We
      suggest routine examination of the pulmonary veins with pulsed Doppler ultrasound
      in every fetus with a prenatally diagnosed heart defect. Such Doppler parameters
      could be used in future as cut-offs for the recently reported in-utero atrial
      septostomy to decompress an obstructed left atrium.

PMID- 16795124
TI  - Analysis of the short form-36 (SF-36): the beta-binomial distribution approach.
AB  - Health-related quality of life (HRQoL) is an important indicator of health status
      and the Short Form-36 (SF-36) is a generic instrument to measure it. Multiple
      linear regression (MLR) is often used to study the relationship of HRQoL with
      patients' characteristics, though HRQoL outcomes tend to be not normally
      distributed, skewed and bounded (e.g. between 0 and 100). A sample of 193
      patients with eating disorders has been analysed to assess the performance of the
      MLR under non-normality conditions. Normal distribution was rejected for seven
      out of the eight domains. A beta-binomial distribution is suggested to fit the SF
      36 scores. The beta-binomial distribution is not rejected for five out of the
      eight domains. Thus, a beta-binomial regression (BBR) is suggested to analyse the
      SF-36 scores. Results using MLR and BBR have been compared for real and simulated
      data. Performance of the BBR is shown to be better than MLR in the HRQoL domains
      with few ordered categories and very similar to MLR in the more continuous
      domains. Moreover, the interpretation of the estimates obtained with BBR is
      clinically more meaningful. A common technique of statistical analysis is
      preferable for all the HRQoL dimensions. Therefore, the BBR approach is
      recommended not only to detect significant predictors of HRQoL when SF-36 is
      used, but also to analyse and interpret the effect of several explanatory
      variables on HRQoL. Further work is required to test the better performance of
      BBR against standard methods for other HRQoL outcomes, populations or
      interventions.

PMID- 16795125
TI  - Reference ranges for Doppler parameters of the fetal aortic isthmus during the
      second half of pregnancy.
AB  - OBJECTIVE: To establish reference ranges for blood flow velocity waveforms (FVW)
      of the fetal aortic isthmus (AoI) during the second and third trimesters of
      pregnancy. METHODS: This was a prospective cross-sectional observational study
      involving 458 uncomplicated singleton pregnancies between 19 and 37 weeks of
      gestation. Fetal AoI Doppler parameters were assessed in either the longitudinal
      aortic arch view or the three vessels and trachea view. Regression analysis was
      used to determine gestational-age-specific reference ranges and to construct
      nomograms for the following Doppler parameters: pulsatility index (PI),
      resistance index (RI) and peak systolic (PSV), end-diastolic (EDV) and time
      averaged maximum (TAMXV) velocities. Intra- and interobserver reproducibility
      were evaluated by calculating intraclass correlation coefficients (ICCs) and
      limits of agreement. RESULTS: Reliable FVW in the AoI were obtained in all cases.
      Acceptable intra- and interobserver reproducibility was obtained. With advancing
      gestation, there was a significant increase in PSV, TAMXV and PI, whereas RI and
      EDV remained constant during the second half of pregnancy. No cases of absent or
      reversed flow during diastole were detected. CONCLUSION: Normal data of the fetal
      AoI blood FVW throughout the second and third trimesters of pregnancy are
      provided. The reported Doppler profiles may be of clinical use in the assessment
      of hemodynamically compromised growth-restricted fetuses.

PMID- 16795126
TI  - The effect of discordance among violence and general recidivism risk estimates on
      predictive accuracy.
AB  - INTRODUCTION: Previous research has shown that the prediction of short-term
      inpatient violence is negatively affected when clinicians' inter-rater agreement
      is low and when confidence in the estimate of risk is low. This study examined
      the effect of discordance between risk assessment instruments used to predict
      long-term general and violence risk in offenders. METHODS: The Psychopathy
      Checklist - Revised (PCL-R), Level of Service Inventory - Revised (LSI-R),
      Violence Risk Appraisal Guide (VRAG), and the General Statistical Information on
      Recidivism (GSIR) were the four risk-prediction instruments used to predict post
      release general and violent recidivism within a sample of 209 offenders. RESULTS:
      The findings lend empirical support to the assumption that predictive accuracy is
      threatened where there is discordance between risk estimates. Discordance between
      instruments had the impact of reducing predictive accuracy for all instruments
      except the GSIR. Further, the influence of discordance was shown to be greater on
      certain instruments over others. Discordance had a moderating effect on both the
      PCL-R and LSI-R but not on the VRAG and GSIR. CONCLUSIONS: There is a distinct
      advantage when attempting to predict recidivism to employing measures such as the
      LSI-R, which includes dynamic variables and intervention-related criminogenic
      domains, over a measure purely of fixed characteristics, such as the GSIR;
      however, if there is discordance between the risk estimates, caution should be
      exercised and more reliance on the more static historically based instrument may
      be indicated.

PMID- 16795127
TI  - Intracardiac Doppler assessment of left valve inflow in first-trimester fetuses
      with increased nuchal translucency: preliminary observations in trisomy 21.
AB  - OBJECTIVES: To perform a qualitative assessment of the pulsed Doppler waveform
      profile at the level of left atrioventricular valve inflow in first-trimester
      fetuses with increased nuchal translucency thickness (NT), in order to compare
      those with trisomy 21 and those with normal karyotype. METHODS: This was a review
      of 285 consecutive fetuses with increased NT. Pulsed Doppler velocity waveforms
      of left atrioventricular valve inflow were recorded. The E-wave, A-wave and
      velocity profile in the aorta were displayed. Cases were classified into two
      patterns: Pattern A included those in which the E-wave velocity crossed the A
      wave before the baseline in all waveforms; Pattern B included those in which the
      lowest E-wave velocity crossed the baseline but not the A-wave in at least one of
      the profiles. The karyotype was determined and the frequency of occurrence of
      Patterns A or B in fetuses with normal karyotype and those with trisomy 21 were
      compared. RESULTS: Of the 285 cases, 230 were assigned to Pattern A and 55 to
      Pattern B. There were 47 cases of trisomy 21, 22 had other chromosomal
      abnormalities, and 212 had a normal karyotype; in four cases the karyotype was
      unknown. Among the 212 karyotypically normal fetuses, five had heart defects,
      five had other structural defects, three suffered spontaneous intrauterine death
      and one was terminated. Pattern A was found in 200/212 (94.3%) cases with normal
      karyotype, in 12/47 (25.5%) cases with trisomy 21, and in 17/22 (77.3%) cases
      with other chromosomal abnormalities. Pattern B was found in 12/212 (5.7%) cases
      with normal karyotype, in 35/47 (74.5%) cases with trisomy 21 (chi-square test, P
      < 0.001), and in 5/22 (22.7%) cases with other chromosomal abnormalities.
      CONCLUSIONS: Intracardiac Doppler qualitative assessment of left valve inflow in
      first-trimester fetuses with increased NT shows differences between normal and
      trisomy 21 fetuses, probably reflecting differences in myocardial function.

PMID- 16795128
TI  - Simple approach to prenatal diagnosis of transposition of the great arteries.
AB  - OBJECTIVE: To analyze the most relevant anomalies, seen in a sequential segmental
      transverse views approach to imaging the fetal heart, that provide clues to the
      diagnosis of complete transposition of the great arteries (TGA). METHODS: We
      reviewed retrospectively all the cases of isolated TGA diagnosed in our center or
      submitted for a second opinion through the spatio-temporal image correlation
      (STIC) telemedicine (TELE-STIC) program. Only transverse cardiac sweeps were
      obtained. Digital video clips and STIC volumes were reviewed. The abnormal
      features on four-chamber, five-chamber, three-vessel (3V) and three vessels and
      trachea (3VT) views were analyzed. RESULTS: The study population consisted of
      eight fetuses with TGA with normal extracardiac anatomy. The gestational age
      ranged from 13 to 32 (mean, 23) weeks. The maternal age ranged from 25 to 42
      (mean, 32) years. A normal four-chamber view was seen in seven cases. Only one
      case demonstrated a significant ventricular septal defect. At the level of the
      five-chamber view a straight course arterial vessel arose from the left ventricle
      with lateral branches in all fetuses. In the 3V view, the ascending aorta was
      seen reaching more anteriorly than was the pulmonary artery in six cases. At the
      level of the 3VT view, two vessels (transverse aortic arch and superior vena
      cava) rather than three were seen in all cases. CONCLUSION: Our proposed
      sequential segmental approach to imaging the fetal heart apparently allows, in
      five-chamber and 3VT views, clear and confident signs to be detected that aid
      diagnosis of TGA.

PMID- 16795129
TI  - Prenatal diagnosis and outcome for fetuses with congenital absence of the
      pulmonary valve.
AB  - OBJECTIVES: To analyze fetal echocardiographic findings of absent pulmonary valve
      syndrome (APVS), its association with chromosomal and extracardiac anomalies
      including nuchal translucency (NT) and the outcome after diagnosis. METHODS: Data
      of 14 fetuses with confirmed APVS retrospectively collected in two tertiary
      referral centers between 1998 and 2004 were analyzed. The variables examined
      were: reason for referral, gestational age at diagnosis and associated
      abnormalities, including first trimester NT thickness. Cardiac evaluation
      included measurement of cardiothoracic ratio, diameter of pulmonary arteries and
      Doppler flow in the pulmonary trunk. Information was retrieved from clinical
      files, recorded videotapes and stored images. Karyotyping including examination
      for the 22q11 deletion was performed in all cases. RESULTS: Mean gestational age
      at diagnosis was 28 weeks, with 5/14 (36%) diagnosed before 22 weeks. In 13/14
      (93%) there was an associated ventricular septal defect (subaortic in 12 fetuses
      and inlet-type in one) and all 13 had tetralogy of Fallot. Enlargement of the
      central pulmonary arteries and cardiomegaly were present in all cases diagnosed
      after 22 weeks. Of the five fetuses in which APVS was detected before 22 weeks,
      four (80%) had a normal pulmonary trunk diameter, two (40%) had normal pulmonary
      branches and three (60%) had normal cardiac size. The arterial duct was absent in
      11/14 (79%). A correlation between presence of the arterial duct and the size of
      the central pulmonary arteries or cardiomegaly could not be established.
      Increased NT was observed in 4/10 cases (40%) for which this information was
      available. 22q11 microdeletion was diagnosed in three fetuses (21%). There were
      five terminations of pregnancy, one intrauterine death, five neonatal deaths and
      one infant death. Of the six neonates with respiratory distress, only one (17%)
      survived and of the eight babies in whom there was an intention to treat, two
      survived (25%). CONCLUSIONS: APVS can be accurately diagnosed by fetal
      echocardiography but screening ultrasound in the mid-second trimester is likely
      to have a low detection rate, probably due to the incomplete expression of the
      disease at this point. Many fetuses with APVS have an increased NT in the first
      trimester and this may help an earlier recognition of the defect. The most common
      associated karyotype anomaly is 22q11 microdeletion. Enlargement of the central
      pulmonary arteries is mainly related to the gestational age at diagnosis. Our
      results confirm that the outlook for these patients is extremely poor.

PMID- 16795130
TI  - A spatial scan statistic for ordinal data.
AB  - Spatial scan statistics are widely used for count data to detect geographical
      disease clusters of high or low incidence, mortality or prevalence and to
      evaluate their statistical significance. Some data are ordinal or continuous in
      nature, however, so that it is necessary to dichotomize the data to use a
      traditional scan statistic for count data. There is then a loss of information
      and the choice of cut-off point is often arbitrary. In this paper, we propose a
      spatial scan statistic for ordinal data, which allows us to analyse such data
      incorporating the ordinal structure without making any further assumptions. The
      test statistic is based on a likelihood ratio test and evaluated using Monte
      Carlo hypothesis testing. The proposed method is illustrated using prostate
      cancer grade and stage data from the Maryland Cancer Registry. The statistical
      power, sensitivity and positive predicted value of the test are examined through
      a simulation study.

PMID- 16795131
TI  - Liquid chromatographic/mass spectrometric assay of rabeprazole in dog plasma for
      a pharmacokinetic study.
AB  - In order to evaluate the pharmacokinetic (PK) profile of rabeprazole (RA) sterile
      powder for injection, a rapid, sensitive and specific assay for quantitative
      determination of RA in dog plasma was developed and validated. After a liquid
      liquid extraction procedure, samples were analyzed by liquid chromatography
      electrospray ionization mass spectrometry (LC-ESI-MS) using omepazole as the
      internal standard (IS). The analyte and IS was chromatographed on a ZORBAX Extend
      C(18) analytical column (50 x 2 mm i.d, 5 microm, Agilent Technologies, USA). The
      assay was linear in the range 1-2000 ng/mL. The lower limit of quantification of
      RA was 1 ng/mL. The recovery of RA was greater than 70%. The within- and between
      batch accuracy was 102.7-107.4% and 103.5-105.7%, respectively. The plasma
      samples for the PK study were collected at defined time points during and after
      an intravenous injection (1 mg/kg) to beagle dogs and analyzed by LC-ESI-MS
      method. The PK parameters, such as half-life, volume of distribution, total
      clearance and elimination rate constant, were determined. The PK profile of RA
      gave insights into the application in the clinics.

PMID- 16795132
TI  - A systematic review of the accuracy of first-trimester ultrasound examination for
      detecting major congenital heart disease.
AB  - OBJECTIVE: To evaluate the accuracy of first-trimester ultrasound examination in
      detecting major congenital heart disease (CHD) using a systematic review of the
      literature. METHODS: General bibliographic and specialist computerized databases
      along with manual searching of reference lists of primary and review articles
      were used to search for relevant citations. Studies were included if a first
      trimester ultrasound scan was carried out to detect CHD that was subsequently
      verified by a reference standard. Data were extracted on study characteristics
      and quality, and 2 x 2 tables were constructed to calculate sensitivity and
      specificity. RESULTS: Ten studies (involving 1243 patients) were suitable for
      inclusion. Of these, four used transabdominal ultrasonography, four used
      transvaginal and two used a combination. Pooled sensitivity and specificity were
      85% (95% CI, 78-90%) and 99% (95% CI, 98-100%), respectively. CONCLUSION:
      Ultrasound examination of the fetus in the first trimester is feasible for
      accurately detecting major CHD. It may be offered to women at high risk of having
      children with CHD.

PMID- 16795133
TI  - Novel application of 4D sonography with B-flow imaging and spatio-temporal image
      correlation (STIC) in the assessment of the anatomy of pulmonary arteries in
      fetuses with pulmonary atresia and ventricular septal defect.
AB  - OBJECTIVES: To assess the reliability of two-dimensional gray-scale (2D) and
      color Doppler echocardiography in the study of the size and anatomy of the
      central pulmonary arteries and of the sources of pulmonary blood flow in a case
      series of fetuses with pulmonary atresia and ventricular septal defect (PA-VSD),
      and to evaluate whether the use of 4D ultrasound with B-flow imaging and spatio
      temporal image correlation (STIC) can improve prenatal diagnostic accuracy.
      METHODS: The study population comprised a group of seven PA-VSD fetuses that had
      been examined by 2D and color Doppler echocardiography exclusively, and a group
      of five additional cases identified initially by conventional echocardiography
      and examined further by 4D ultrasound, for all of which a thorough postnatal or
      autopsy study of the size and anatomy of the pulmonary arteries and blood supply
      was available. RESULTS: 2D and color Doppler echocardiography failed to assess
      the anatomy of the central pulmonary arteries and the source of the pulmonary
      blood supply in 33% and 25% of the 12 cases, respectively. 4D ultrasound with B
      flow imaging and STIC assessed successfully the anatomy of the pulmonary arteries
      and the source of pulmonary blood supply in all five fetuses examined.
      CONCLUSIONS: The prognosis of PA-VSD is influenced by the anatomy of the
      pulmonary arteries and the sources of the pulmonary blood supply, and by
      coexisting extracardiac and genetic anomalies. Our findings, although limited to
      a small sample size, suggest that 4D echocardiography with B-flow imaging and
      STIC, unlike 2D ultrasound, can provide thorough visualization of very small
      vessels and of the arterial blood supply to the lungs of fetuses with PA-VSD. 4D
      ultrasound may be used in the future to improve and help to detail the diagnosis
      of other fetal cardiac defects.

PMID- 16795135
TI  - Development of hypoplastic left heart syndrome after diagnosis of aortic stenosis
      in the first trimester by early echocardiography.
AB  - We describe a case of aortic stenosis in the first trimester that progressed to
      hypoplastic left heart syndrome. At 11 + 3 weeks' gestation the four-chamber view
      was normal but evidence of increased aortic blood velocity prompted the diagnosis
      of aortic outflow obstruction. At 16 + 6 weeks' gestation the left ventricle was
      hyperechogenic, globular and dysfunctional, suggesting the development of
      hypoplastic left heart syndrome. The aortic valve was small and there was no flow
      across the mitral or aortic valves. From 17 + 3 weeks increased reversed flow in
      the pulmonary veins suggested restriction of the foramen ovale. Follow-up
      echocardiographic examinations were performed every 2-3 weeks until delivery at
      term. Postnatal intervention included a Norwood I operation performed on the 5th
      postnatal day. We have shown the feasibility and utility of early fetal
      echocardiography and that a left heart obstruction diagnosed in the first
      trimester can progress to left heart hypoplasia during the early second
      trimester. This information is important for planning prenatal and perinatal
      management.

PMID- 16795134
TI  - Ultrasound-guided injection and occlusion of the trachea in fetal sheep.
AB  - OBJECTIVES: To access the fetal sheep trachea by ultrasound-guided transthoracic
      injection in order to deliver gene therapy vectors or occlude the trachea with a
      detachable balloon. METHODS: Fetal sheep were operated on at a mean gestational
      age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance,
      either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an
      occlusive balloon) needle was inserted via the fetal thorax into the fetal
      trachea. RESULTS: Using the 20-G spinal needle the trachea was accessed
      successfully in 33/36 fetuses, with 97% survival. Failure to inject was related
      to fetal position and gestational age. Blood vessel damage causing significant
      morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by
      puncturing the trachea with the 16-G needle and advancing an endoluminal balloon
      in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100%
      survival. In one case, the balloon became sited within the accessory lobe
      bronchus and was not inflated. At postmortem examination 21 days later, all
      balloons remained inflated and occluded the trachea, and the lung-to-body weight
      ratio and airways morphometric indices were consistent with relative pulmonary
      hyperplasia in the obstructed lungs. CONCLUSIONS: Ultrasound-guided transthoracic
      tracheal puncture is a reliable technique in fetal sheep, with low morbidity and
      mortality. Using this technique, a detachable endotracheal balloon can be placed
      to provoke pulmonary growth. Advances in needle design and balloon size may
      improve the success rate.

PMID- 16795136
TI  - In-utero pericardiocentesis to treat fetal hydrops caused by X-linked chronic
      granulomatous disease.

PMID- 16795137
TI  - Determination of artemisinin in human serum by high-performance liquid
      chromatography with on-line UV irradiation and peroxyoxalate chemiluminescence
      detection.
AB  - Artemisinin is an antimalarial drug containing an internal endoperoxide linkage
      in its structure. A simple, selective and sensitive high-performance liquid
      chromatography (HPLC)-peroxyoxalate chemiluminescence (PO-CL) method for the
      determination of artemisinin was developed. This method is based on the fact that
      endoperoxide in artemisinin structure can be converted to hydrogen peroxide
      (H(2)O(2)) under ultraviolet (UV) irradiation and the generated hydrogen peroxide
      can be measured using PO-CL detection. The HPLC-PO-CL system was optimized on a
      mobile phase, post column chemiluminescence reagent, UV source and irradiation
      time. In addition, the system was combined with simple liquid-liquid extraction
      using n-hexane that allowed selective and sensitive determination of artemisinin
      in serum. The limit of detection using 0.5 mL of blood was 0.062 micromol/L (17.5
      ng/mL) at a signal-to-noise ratio of 3. Calibration curve obtained for
      artemisinin in human serum 4-80 micromol/L (1.1-22.6 microg/mL) showed a good
      linearity (r = 0.999).

PMID- 16795138
TI  - What we don't know about prayer...

PMID- 16795139
TI  - High cholesterol can be a pain.

PMID- 16795140
TI  - Exercise and cardiac arrest.

PMID- 16795141
TI  - FDA notifications. HIV-1 adult treatment guidelines are updated.

PMID- 16795142
TI  - FDA notifications. Two tenofovir containing products are approved.

PMID- 16795143
TI  - Genetics of autoimmune diseases. Proceedings of the Serono Symposia International
      Conference. March 18-20, 2005. Cannes, France.

PMID- 16795144
TI  - Optical and electrochemical detection techniques for cell-based microfluidic
      systems.
AB  - The ability to fabricate microfluidic systems with complex structures and with
      compatible dimensions between the microfluidics and biological cells have
      attracted significant attention in the development of microchips for analyzing
      the biophysical and biochemical functions of cells. Just as cell-based
      microfluidics have become a versatile tool for biosensing, diagnostics, drug
      screening and biological research, detector modules for cell-based microfluidics
      have also undergone major development over the past decade. This review focuses
      on detection methods commonly used in cell-based microfluidic systems, and
      provides a general survey and an in-depth look at recent developments in optical
      and electrochemical detection methods for microfluidic applications for
      biological systems, particularly cell analysis. Selected examples are used to
      illustrate applications of these detection systems and their advantages and
      weaknesses.

PMID- 16795145
TI  - Controversial topics in surgery. The case against radical prostatectomy.

PMID- 16795146
TI  - Construction of an active acetohydroxyacid synthase I with a flexible linker
      connecting the catalytic and the regulatory subunits.
AB  - Acetohydroxyacid synthase I (AHAS I), one of three isozymes in Escherichia coli
      catalyzing the first common step in the biosynthesis of branched amino acids, is
      composed of two kinds of subunits. The large catalytic (B) and small regulatory
      (N) subunits of the holoenzyme dissociate and associate freely and rapidly and
      are quite different in size, charge and hydrophobicity, so that high resolution
      purification methods lead to partial separation of subunits and to heterogeneity.
      We have prepared several linked AHAS I proteins, in which the large subunit B
      with a hexahistidine-tag at the N-terminus, was covalently joined by a flexible
      linker, containing several (X) amino acids, to the small subunit N to form His6
      BuXN polypeptides. All linked BuXN polypeptides have similar specific activity,
      sensitivity to valine and substrate specificity as the wild type holoenzyme. The
      most successful BuXN linked protein (Bu30N-r) was inserted into and expressed in
      yeast and its catalytic properties were tested.

PMID- 16795149
TI  - Controversial topics in surgery. The case for open repair.

PMID- 16795150
TI  - An inactivated subvirion influenza A (H5N1) vaccine.

PMID- 16795151
TI  - Gatifloxacin and dysglycemia in older adults.

PMID- 16795152
TI  - Case 7-2006: a man with altered mental status and acute renal failure.

PMID- 16795153
TI  - Case 7-2006: a man with altered mental status and acute renal failure.

PMID- 16795154
TI  - Blues plot transparency. Distinction plan promises to improve level of care.

PMID- 16795155
TI  - Effects of teacher attention on study behavior.
AB  - The effects of contingent teacher attention on study behavior were investigated.
      Individual rates of study were recorded for one first-grade and five third-grade
      pupils who had high rates of disruptive or dawdling behavior. A reinforcement
      period (in which teacher attention followed study behavior and non-study
      behaviors were ignored) resulted in sharply increased study rates. A brief
      reversal of the contingency (attention occurred only after periods of non-study
      behavior) again produced low rates of study. Reinstatement of teacher attention
      as reinforcement for study once again markedly increased study behavior. Follow
      up observations indicated that the higher study rates were maintained after the
      formal program terminated.

PMID- 16795156
TI  - Reinforcer sampling: a technique for increasing the behavior of mental patients.
AB  - Mental hospital patients in a motivating ward environment were using the
      available reinforcers less than was desired. A procedure for increasing the
      frequency of using reinforcers was developed: all patients were required to
      engage in the reinforcing event each time it was available but the duration of
      this required participation was limited so that the event was merely sampled. The
      effect of this required sampling was experimentally evaluated for three different
      reinforcers: going for a walk, watching a movie, and attending a music session.
      More patients used each of the three reinforcers and to a greater extent when the
      sampling procedure was used. Participation was increased even for those patients
      who had already been using the reinforcers, demonstrating that the technique did
      more than provide simple familiarization. Some familiarization was involved since
      the participation was slightly increased even after the sampling procedure was
      discontinued. The technique appears to be especially applicable when reinforcers
      are being delivered infrequently.

PMID- 16795157
TI  - The effects and side effects of punishing the autistic behaviors of a deviant
      child.
AB  - Timeout procedures in the home and extinction and reinforcement of incompatible
      behaviors in the laboratory failed to eliminate the disruptive and dangerous
      climbing behavior of a deviant child. Punishment with electric shock was used to
      eliminate this behavior in the laboratory and then in the home. The effects were
      reversible and were restricted to specific stimulus conditions. A less severe
      form of punishment was used to eliminate the child's autistic rocking. Other
      behaviors of the subject were continuously measured in the laboratory to
      determine the side effects of punishment. No suppression of other behaviors
      correlated with punishment was noted. However, the rate of some behaviors
      increased when punishment was used to eliminate deviant behaviors, but these
      increases were, primarily, desirable.

PMID- 16795158
TI  - Production and elimination of disruptive classroom behavior by systematically
      varying teacher's behavior.
AB  - The effects of teacher behaviors on the classroom behaviors of children were
      investigated by systematically varying approving (praise, smiles, contacts, etc.)
      and disapproving (verbal reprimands, physical restraint, etc.) classes of teacher
      behavior. Measures were taken on both teacher and child behaviors. Each day a
      sample of 10 children was observed. The subject pool was a class of 28 well
      behaved children in a middle-primary public school class. The results
      demonstrated that approving teacher responses served a positive reinforcing
      function in maintaining appropriate classroom behaviors. Disruptive behaviors
      increased each time approving teacher behavior was withdrawn. When the teacher's
      disapproving behaviors were tripled, increases appeared most markedly in the
      gross motor and noise-making categories of disruptive behavior. The findings
      emphasize again the important role of the teacher in producing, maintaining, and
      eliminating disruptive as well as pro-social classroom behavior.

PMID- 16795159
TI  - Modification of a child's problem behaviors in the home with the mother as
      therapist.
AB  - Differential consequences were used to increase obedience and decrease aggressive
      behavior in a four-and-one-half year old boy. Treatment was conducted in the
      child's home by his mother.

PMID- 16795160
TI  - Applying "group" contingencies to the classroom study behavior of preschool
      children.
AB  - A group of 12 children were enrolled in a preschool class. During the first
      experimental stage they participated in special events contingent on token
      earning. Tokens were acquired by engaging in a variety of study behaviors. After
      a level of study behavior was established under this contingency, the special
      events were provided noncontingently. Study behavior declined throughout the
      noncontingent stage. Reestablishing the original contingencies produced an
      immediate return to the initial level of study behavior. Noncontingent special
      events reduced the amount of independent study, group participation, and
      cooperative study. The study behavior of each child was altered in the same
      direction, though differences in the magnitude of effects from child to child
      were observed.

PMID- 16795161
TI  - The effects of shock as a punisher for cigarette smoking.
AB  - An attempt was made to reduce the cigarette smoking of three subjects by means of
      a special cigarette case that delivered aversive shock when opened. The number of
      cigarettes smoked was recorded by a counter in the cigarette case. The validity
      of the counter readings as a measure of smoking was obtained by a specially
      designed participant-observer technique. It was found that the rate of smoking
      decreased as a function of the intensity of the shock. Also, the smoking returned
      to its previously unpunished level after the shock punisher was discontinued.
      Both of these findings confirm the results of laboratory studies of punishment of
      simpler responses and extends them to more complex responses in a naturalistic
      situation. Surprisingly, the duration for which the apparatus was worn also
      decreased as a function of the intensity of the shock. This finding reveals that
      this aversive shock technique produced avoidance behavior that prevents the
      technique from having extensive applicability for eliminating smoking. The same
      limitation may apply to the use of aversive shock for eliminating other
      undesirable behaviors.

PMID- 16795162
TI  - Effect of contingent and non-contingent social reinforcement on the cooperative
      play of a preschool child.
AB  - The effect of adult social reinforcement on the cooperative play of a five-year
      old girl in a preschool setting was assessed under two conditions: (1) presented
      randomly throughout the school day, and (2) presented contingent on cooperative
      play. Only in the latter condition was a significant change in cooperative play
      observed.

PMID- 16795163
TI  - A reliable wrist counter for recording behavior rates.

PMID- 16795164
TI  - "Good-bye, teacher...".

PMID- 16795165
TI  - Some current dimensions of applied behavior analysis.

PMID- 16795167
TI  - Effects of candy and social reinforcement, instructions, and reinforcement
      schedule leaning on the modification and maintenance of smiling.
AB  - Two retarded boys exhibited abnormally low rates of smiling. In Exp. I, the
      frequency of a boy's smiling was first increased with candy reinforcement, but
      the frequency of the response did not decrease when candy reinforcement was
      terminated. When the subject wore a sign designed to make social interactions
      contingent on not-smiling, the frequency of smiling decreased. The sign was then
      changed to make social interactions contingent on smiling and the rate of smiling
      increased. In Exp. II, a second boy initially never smiled. Establishment of a
      contingency for candy reinforcement did not increase this zero response rate.
      Instructing the child to smile initially increased smiling, but the instructions
      then became progressively more ineffective. Candy reinforcement increased the
      rate of smiling to a normal range, but the rate of the response promptly
      decreased when this reinforcement was discontinued. Continuous candy
      reinforcement was again employed to increase the response rate and then
      progressively leaner schedules of variable-ratio candy reinforcement were
      employed. Consequently, the rate of smiling did not decrease when candy
      reinforcement was again eliminated. Subsequently, signs were employed to regulate
      social interactions and the rate of smiling was shown to be controlled by these
      interactions serving as reinforcers.

PMID- 16795166
TI  - Establishing use of descriptive adjectives in the spontaneous speech of
      disadvantaged preschool children.
AB  - From observer records, a count was made for each child, in a group of
      disadvantaged children in an experimental preschool, of usage and acquisition of
      descriptive adjectives, with and without noun referents. Procedures were sought
      which would effectively modify the low rates of adjective-noun combinations in
      the everyday language of all the children. Time in school, intermittent teacher
      praise, and social and intellectual stimulation were not effective in changing
      the low rates of using adjectives of size and shape. Group teaching effectively
      increased rates of using color- and number-noun combinations in the group
      teaching situation, but was ineffective in changing rates of usage in the
      children's "spontaneous" vocabularies. By operating directly on the children's
      language in the free-play situation, making access to preschool materials
      contingent upon use of a color-noun combination, significant increases in such
      usage were effected in the spontaneous vocabularies of all the children.
      Preschool materials apparently functioned as powerful reinforcers. Though
      traditional teaching procedures were effective in generating adjective-noun
      combinations in that restricted situation, it was only through application of
      environmental contingencies that color names as descriptive adjectives were
      effectively and durably established in all the children's spontaneous
      vocabularies.

PMID- 16795168
TI  - A manual counter for recording multiple behavior.

PMID- 16795169
TI  - Feedback in behavior modification: an experimental analysis in two phobic cases.
AB  - Two illustrations of single-case research are described in which an isolated
      therapeutic variable was sequentially introduced, withdrawn, and reintroduced
      while changes in a clinically relevant behavior were measured. A claustrophobic
      patient and a knife-phobic patient received graduated practice in facing their
      phobic stimuli; length of time the claustrophobic patient stayed in a small dark
      room per trial, and length of time the knife-phobic patient kept knife exposed
      per trial were measured. In both experiments, when feedback of these time scores
      was withdrawn, ongoing progress was retarded. Reinstatement of feedback led to
      renewed improvement. In Experiment 2, adding and removing contingent verbal
      praise against a constant background of precise feedback did not significantly
      alter rate of progress.

PMID- 16795170
TI  - Rules, praise, and ignoring: elements of elementary classroom control.
AB  - An attempt was made to vary systematically the behavior of two elementary school
      teachers to determine the effects on classroom behavior of Rules, Ignoring
      Inappropriate Behaviors, and showing Approval for Appropriate Behavior. Behaviors
      of two children in one class and one child in the other class were recorded by
      observers, as were samples of the teachers' behavior. Following baseline
      recordings, Rules, Ignoring, and Approval conditions were introduced one at a
      time. In one class a reversal of conditions was carried out. The main conclusions
      were that: (a) Rules alone exerted little effect on classroom behavior, (b)
      Ignoring Inappropriate Behavior and showing Approval for Appropriate Behavior (in
      combination) were very effective in achieving better classroom behavior, and (c)
      showing Approval for Appropriate Behaviors is probably the key to effective
      classroom management.

PMID- 16795171
TI  - An experimental analysis of verbal imitation in preschool children.
AB  - A model presented English words to three preschool children and reinforced
      accurate imitation of these words. The model also presented novel Russian words
      but the subjects' imitation of these words was never reinforced. As long as the
      subjects' imitation of English words was reinforced, their accuracy of imitating
      non-reinforced Russian words increased. When reinforcement was not contingent
      upon imitation of English words, accuracy of imitating both the English and the
      Russian words decreased. These results support and extend previous work on
      imitation.

PMID- 16795172
TI  - A miniature, portable timer and audible signal-generating device.

PMID- 16795173
TI  - Operant control of eye movements.
AB  - In a monitoring situation eye movements were required in order for signals to be
      presented. Detection of signals was the reinforcement. A multiple schedule of
      fixed-interval reinforcement, differential reinforcement of low rate, and fixed
      ratio reinforcement was established for eye movements. Results demonstrated that
      an eye movement can act as an operant controlled by its consequences. Operant
      control of eye movements has important implications for human factor analysts
      concerned with "attention".

PMID- 16795174
TI  - Collateral social development accompanying reinforcement of outdoor play in a
      preschool child.
AB  - A 3-yr-old preschool girl with deficits in both motor and social repertoires was
      socially reinforced by teachers for use of outdoor play equipment, as a
      contribution to her motor skills and as a tactic to produce increased social
      contact with other children. Her use of outdoor play equipment, and various
      examples of her social interaction with both teachers and children were scored in
      the course of experimental development and analysis of her rate of equipment use.
      Equipment use increased greatly under the social reinforcement contingency;
      certain desirable examples of social interaction with other children showed a
      collateral development; other examples of adult-oriented development remained
      constant; and one class of undesirable baby-like behavior decreased markedly.
      Thus, the study provided a picture of what other behavior changes may take place
      in the course of behavior modification aimed at a single response class.

PMID- 16795175
TI  - A method to integrate descriptive and experimental field studies at the level of
      data and empirical concepts.
AB  - It is the thesis of this paper that data from descriptive and experimental field
      studies can be interrelated at the level of data and empirical concepts if both
      sets are derived from frequency-of-occurrence measures. The methodology proposed
      for a descriptive field study is predicated on three assumptions: (1) The primary
      data of psychology are the observable interactions of a biological organism and
      environmental events, past and present. (2) Theoretical concepts and laws are
      derived from empirical concepts and laws, which in turn are derived from the raw
      data. (3) Descriptive field studies describe interactions between behavioral and
      environmental events; experimental field studies provide information on their
      functional relationships. The ingredients of a descriptive field investigation
      using frequency measures consist of: (1) specifying in objective terms the
      situation in which the study is conducted, (2) defining and recording behavioral
      and environmental events in observable terms, and (3) measuring observer
      reliability. Field descriptive studies following the procedures suggested here
      would reveal interesting new relationships in the usual ecological settings and
      would also provide provocative cues for experimental studies. On the other hand,
      field-experimental studies using frequency measures would probably yield findings
      that would suggest the need for describing new interactions in specific natural
      situations.

PMID- 16795176
TI  - Behavioral engineering: postural control by a portable operant apparatus.
AB  - Recent studies suggested a general behavioral engineering approach to behavioral
      disorders by portable operant treatment instruments. The approach was applied to
      the problem of poor posture, specifically rounding of the back or slouching. An
      apparatus was developed that provided a warning stimulus followed by an aversive
      tone for the duration of slouching. Slouching was thereby punished by onset of
      the tone, and non-slouching was reinforced by tone termination and postponement.
      Twenty-five adults wore the apparatus during their normal working day during
      alternate periods in which the aversive tone was connected and disconnected
      experimentally. A miniature time-meter recorded the duration of slouching. The
      results showed that slouching decreased for each subject during each period in
      which slouching produced the aversive tone. For two subjects, a second control
      procedure was applied in which slouching terminated the tone. The result was an
      increase of slouching, demonstrating that the postural changes were controlled by
      the scheduled relation between the aversive tone and the response, and not by
      other factors such as simple response feedback. The substantial changes in
      posture indicate that the present procedure may prove to be an effective
      treatment alternative and suggests the general value of the behavioral
      engineering approach.

PMID- 16795177
TI  - Behavioral engineering: the reduction of smoking behavior by a conditioning
      apparatus and procedure.
AB  - Recent findings from animal conditioning studies have revealed methods of
      reducing responses to a very low level with a minimum of aversive by-products.
      These findings were incorporated into the design of a cigarette case that
      automatically locked itself for a period of time after a cigarette was removed
      from it. The next cigarette could be taken at the end of the interval, which was
      signalled by distinctive stimuli. Five heavy smokers were allowed to become
      accustomed to using the case. Then, the duration for which the case was locked
      was gradually increased over a period of weeks to about 1 hr. Smoking gradually
      decreased to the target level of about one-half of a package of cigarettes per
      day. Control procedures showed that specific features of the apparatus were
      responsible for the reduction of smoking. The results indicated that this
      apparatus was sufficiently effective, convenient, and acceptable to smokers to
      constitute a practical procedure for reducing smoking to the level considered
      medically safe. The procedure may also have potential for reducing other habit
      forming or addictive behaviors.

PMID- 16795178
TI  - Generalization of punishment effects-a case study.
AB  - Response-contingent electric shock was evaluated in a laboratory and criterion
      situation before using it to eliminate infrequent and unpredictable biting and
      destructive acts from the repertoire of a retarded adolescent. Although the
      initial results were dramatic, the effects of shock were highly discriminated and
      the therapeutic objectives were not accomplished. The study demonstrates the
      power and some limitations of shock punishment and is presented so that others
      will be better prepared for problems that may arise before the goals of a program
      involving shock punishment will be realized.

PMID- 16795179
TI  - Achievement Place: token reinforcement procedures in a home-style rehabilitation
      setting for "pre-delinquent" boys.
AB  - Token reinforcement procedures were designed to modify the behavior of "pre
      delinquent" boys residing in a community-based, home-style rehabilitation
      setting. Points (the tokens) were redeemable for various privileges such as
      visiting their families, watching TV, and riding bicycles. Points were given by
      the house-parents contingent upon specified appropriate behavior and taken away
      for specified inappropriate behavior. The frequencies of aggressive statements
      and poor grammar decreased while tidiness, punctuality, and amount of homework
      completed increased. It was concluded that a token reinforcement procedure,
      entirely dependent upon back-up reinforcers naturally available in a home-style
      treatment setting, could contribute to an effective and economical rehabilitation
      program for pre-delinquents.

PMID- 16795180
TI  - Some experiments on the organization of a class of imitative behaviors.
AB  - A retarded child was taught to imitate diverse demonstrations made by an
      experimenter, until new demonstrations were imitated correctly upon first
      presentation without direct training. These imitations could be maintained
      without reinforcement, when they were distributed among other reinforced
      imitations. Factors responsible for the continued performance of these
      unreinforced imitations were examined. When subjected to massed extinction
      trials, unreinforced imitations eventually disappeared; they reappeared when
      again interspersed among reinforced imitations. In addition, the stimulus
      function of "similarity of response between subject and experimenter" was
      examined. The subject was taught a set of non-imitative responses, through
      discriminative stimuli controlled by the experimenter, and a comparable imitative
      set. Unreinforced non-imitations, like reinforced imitations, were maintained
      only when interspersed among reinforced imitations. When all reinforcement was
      discontinued, all responses extinguished similarly, indicating that reinforcement
      was necessary to maintain the response-class organization, but not confirming an
      essential role for "similarity" as such.

PMID- 16795181
TI  - Control of tantrum behavior by operant techniques during experimental verbal
      training.
AB  - A technique of controlling undesirable or disruptive behavior during an ongoing
      program of verbal training with a retardate is described. The technique required
      that the stimulus materials of the verbal training program be graded according to
      difficulty, i.e., in terms of the length and complexity of the stimulus
      materials. (This resulted in an initial grading of the stimulus materials into
      different levels of probability of reinforcement.) Changes by the experimenter
      from high-difficulty to low-difficulty stimuli for two trials contingent upon
      disruptive behavior increased the rate of that behavior; changes from low
      difficulty to high-difficulty stimuli for two trials contingent upon disruptive
      behavior decreased its rate. Thus, contingent alternation of the stimulus
      materials of the ongoing training program controlled the frequency of undesirable
      behaviors within the experimental sessions. This technique may comprise an
      alternative to other procedures which require punishment or timeout from the
      ongoing program.

PMID- 16795182
TI  - The use of positive reinforcement in conditioning attending behavior.
AB  - Individual conditioning techniques were applied in a controlled setting to
      increase attending behavior of an underachieving 9-yr-old male subject. The
      procedure involved: (1) determining a stable response pattern, (2) introducing a
      treatment variable to establish a high rate of task-attending behavior, (3)
      measuring the effect of withdrawal of the treatment variable after attaining
      criterion performance, and (4) transferring control to the classroom. The
      interval of attending behavior required for reinforcement was systematically
      increased from 30 sec to 600 sec as the behavior came under experimental control.
      Manipulating the reinforcing contingencies measurably changed the proportion of
      attending behavior and the frequency and duration of non-attending events. Once
      the behaviors were under experimental control, procedures were established to
      program generalization and to maintain the behavior outside the experimental
      setting.

PMID- 16795183
TI  - Rapid computation of rates with a simple nomogram.

PMID- 16795184
TI  - The role of social and material reinforcers in increasing talking of a
      disadvantaged preschool child.
AB  - Adult social reinforcement and access to materials in the preschool were made
      contingent on the verbalizations of a 4-yr-old Negro girl with an extremely low
      frequency of talking. Though the teachers' social attention was always given
      immediately for all spontaneous speech, if the child's spontaneous verbalizations
      were requests for materials, those materials were withheld until she had
      responded to the teachers' questions about those materials. When she was silent,
      the teachers withheld their attention and the materials. A high frequency of
      verbal behavior was quickly established. When both teacher attention and
      materials were provided only when the child was not verbalizing, the child's
      frequency of talking immediately decreased. When social attention and materials
      were again made contingent upon spontaneous speech and answering questions, the
      child's frequency of talking quickly increased to its previous high level. The
      content of the child's verbal behavior which increased was primarily a repetition
      of requests to the teachers with little change noted in the non-request
      verbalizations, or verbalizations to other children. A further experimental
      analysis demonstrated that social interaction per se was not the reinforcer which
      maintained the increased verbalization; rather, for this child, the material
      reinforcers which accompanied the social interaction appeared to be the effective
      components of teacher attention.

PMID- 16795185
TI  - A technique for controlling behavior in natural life settings.
AB  - A behavior control technique is presented, consisting primarily of having a
      patient give up some portion of his reinforcers (usually money) with the
      understanding that he must behave in therapeutically prescribed ways in his
      natural environment to re-earn the reinforcers. The critical features and
      requirements of the technique are discussed, various applications are suggested,
      and implications for research are drawn.

PMID- 16795186
TI  - Developing correspondence between the non-verbal and verbal behavior of preschool
      children.
AB  - Correspondence was developed between children's non-verbal and verbal behavior
      such that their non-verbal behavior could be altered simply by reinforcing
      related verbal behavior. Two groups of six children each were given food snack at
      the end of the day: for reporting use of a specific preschool material during
      free play (procedure A); and then only for reports of use which corresponded to
      actual use of that material earlier that day (procedure B). Initially, procedure
      A alone had little or no effect on the children's use of materials. Procedure B
      resulted in all of the children in one group actually using a specific material,
      and after repeating procedures A and B with this group across a series of
      different materials, procedure A alone was sufficient to significantly increase
      use of a specific material. Correspondence between verbal and non-verbal behavior
      was produced such that, in this group of 4-yr-old disadvantaged Negro children,
      "saying" controlled "doing" 22 or more hours later. In the second group,
      procedure B initially did not increase the use of a specific material; rather,
      the children's reports decreased so as to correspond to the intermittent use of
      the material. It appeared from subsequent procedures with this group that
      maintenance of a high level of reporting was crucial to the saying-then-doing
      correspondence seen in the first group.

PMID- 16795187
TI  - A synchronization effect and its application to stuttering by a portable
      apparatus.
AB  - The present study attempted to determine how a rhythmic beat affects ongoing
      behavior. A regular stimulus beat was presented to normal subjects who had been
      instructed to push a bar from side to side. Other subjects had been instructed to
      emit a vocal response. The individual vocal and motor responses became
      synchronized with the individual beats of the rhythm. The time between stimulus
      beats determined the modal interresponse time. These results indicate a
      synchronization effect: ongoing behavior tends to become synchronized with an
      ongoing stimulus rhythm. An attempt was made to apply these findings to the
      problem of stuttering, which can be considered as a disturbance of the natural
      rhythm of speech. Stutterers were instructed to synchronize their speech with a
      simple regular beat presented to them tactually by a portable apparatus. The
      result was a reduction of 90% or more of the stuttering for each subject during
      the period of synchronization. This effect endured for extended periods of
      spontaneous speech as well as for reading aloud and was found to be attributable
      to the rhythmic nature of the stimulus and not to other factors.

PMID- 16795188
TI  - An experimental analysis of linguistic development: the productive use of the
      plural morpheme.
AB  - Operant conditioning procedures were used to establish a generative use of the
      plural morpheme in the speech of a severely retarded girl. During training
      trials, reinforcement was presented contingent upon correct imitation of singular
      and plural verbalizations by the experimenter, in response to objects presented
      to the subject singly and in pairs. A generative productive plural usage
      resulted, the girl correctly labeling new objects in the singular or plural
      without further direct training relevant to those objects. After establishing the
      singular/plural usage, the contingencies were reversed (reinforcement of plural
      responses to single objects, and vice-versa). This produced a corresponding
      reversal of response by the child. The original usage was then recovered by
      returning to the previous contingencies. A second experiment analyzed certain
      error responses occurring during the first experiment, and further probed the
      generative nature of the subject's plural usage. It was found that errors were
      somewhat more likely to occur in the pluralization of words ending in vowels than
      of words ending in consonants. Furthermore, several words whose plurals had been
      learned according to the reversed plural rule, when examined later during
      reinforcement of normal plural usage, were found then to exemplify the normal
      rule being reinforced, yet without direct training.

PMID- 16795189
TI  - The effects of reinforcement on the modification, maintenance, and generalization
      of social responses of mental patients.
AB  - Social greeting responses of three withdrawn, chronic schizophrenics were
      experimentally modified. Initially, none of the subjects spoke to an
      experimenter. Prompts and cigarette reinforcement were employed to produce
      increases in the rates of greetings. Then, the prompts were faded so that the
      greetings came under the control of the presence of the experimenter. Reversal
      and subsequent reinforcement procedures were employed to demonstrate that the
      responses were controlled by their consequences. Next, the schedule of cigarette
      reinforcement was leaned out so that greetings continued to occur in the absence
      of cigarette reinforcement. However, low or zero rates of greetings occurred in
      the presence of a second experimenter. Five new experimenters employed the
      prompting, fading, reinforcement, and schedule-leaning procedures. Subsequently,
      all subjects emitted appropriately high rates of greetings in the presence of the
      second experimenter. Without further application of the experimental procedures,
      greetings were still occurring in the presence of both the first and second
      experimenters almost three months later.

PMID- 16795190
TI  - Instructing beginning teachers in reinforcement procedures which improve
      classroom control.
AB  - Systematic reinforcement procedures were used to increase study behavior in the
      classrooms of three beginning teachers experiencing problems of classroom
      control. Classroom study rates were recorded during a baseline period. During
      subsequent experimental periods, the teachers changed one or more reinforcement
      contingencies (teacher attention, length of between-period break, a classroom
      game) to bring about increased study rates and concomitant reductions in
      disruptive behaviors. A brief reversal period, in which these contingencies were
      discontinued, again produced low rates of study. Reinstatement of the
      contingencies resulted once again in marked increases in study behaviors.

PMID- 16795191
TI  - Reinforcement therapy in the classroom.
AB  - Teachers were trained in the systematic use of attention and praise to reduce the
      disruptive classroom behavior of four first-grade children. Observation measures
      showed a significant improvement from baseline to treatment for these children
      and no significant changes for same-class controls. While the amount of teacher
      attention to target children remained the same from baseline to treatment, the
      proportion of attention to task-relevant behavior of these children increased.
      Psychological tests revealed no adverse changes after treatment.

PMID- 16795192
TI  - Effects of manipulating an antecedent event on mathematics response rate.
AB  - The purpose of this investigation was to assess the effects on performance rate
      of simply writing the answers to mathematics problems versus verbalizing the
      problems before making a written response. The subject was an 11-yr-old boy whose
      response accuracy on mathematics problems was very erratic. Three experiments
      were conducted, each consisting of three phases. In each first phase, the subject
      was requested to write the answers to sets of mathematics problems. In the
      second, he was required to verbalize the problem before writing the answer. In
      the third phase, the subject was told to write the answer again without prior
      verbalization. The results indicated that the subject's correct answer rate
      increased and his error rate decreased as a result of his verbalizing the
      problems before making a written response. Results further revealed that in the
      final phase of each experiment, the return to the original conditions, his
      correct answer rate continued to increase.

PMID- 16795193
TI  - Application of a simple recording system to the analysis of free-play behavior in
      autistic children.
AB  - An observational system, which has been developed to facilitate recording of the
      total behavioral repertoire of autistic children, involves time-sampling
      recording of behavior with the help of a common Stenograph machine. Categories
      which exhausted all behavior were defined. Each category corresponded with a
      designated key on the Stenograph machine. The observer depressed one key at each
      1-sec interval. The observer was paced by audible beats from a metronome. A naive
      observer can be used with this method. The observer is not mechanically limited
      and a minimum of observer training is required to obtain reliable measures. The
      data sampled during a five-week observation period indicated the stability of a
      taxonomic instrument of behavior based upon direct, time-sampling observations
      and the stability of spontaneous autistic behavior. Results showed that the
      behavior of the subjects was largely nonrandom and unsocialized in character.

PMID- 16795194
TI  - A touch-detecting teaching machine with auditory reinforcement.
AB  - This teaching machine has been designed and used to train reading and other
      visual discrimination skills with normal and retarded children. On each frame the
      subject responds by touching one of three response panels on which are projected
      the multiple-choice alternatives. The response panels are coated with a
      transparent conducting film which allows electronic detection of this simple and
      direct response. Correct responses are reinforced by the machine naming the
      stimulus, while auditory reinforcement is absent for an incorrect response. The
      subject's performance level is continuously computed as an exponentially weighted
      moving average. The measure is weighted so that it rapidly follows recent changes
      in performance.

PMID- 16795195
TI  - An automated system for reinforcing and recording retardate work behavior.

PMID- 16795196
TI  - Modification of social withdrawal through symbolic modeling.
AB  - The present experiment was designed to test the efficacy of symbolic modeling as
      a treatment to enhance social behavior in preschool isolates. Nursery school
      children who displayed marked social withdrawal were assigned to one of two
      conditions. One group observed a film depicting increasingly more active social
      interactions between children with positive consequences ensuing in each scene,
      while a narrative soundtrack emphasized the appropriate behavior of the models. A
      control group observed a film that contained no social interaction. Control
      children displayed no change in withdrawal behavior, whereas those who had the
      benefit of symbolic modeling increased their level of social interaction to that
      of non-isolate nursery school children.

PMID- 16795197
TI  - Increased communications of chronic mental patients by reinforcement and by
      response priming.
AB  - An attempt was made to increase the frequency with which chronic schizophrenic
      patients suggested feasible improvements in their treatment. A response priming
      procedure was devised that was comparable to a previously developed reinforcer
      exposure procedure. The patients were required to attend a structured meeting
      during which they were prompted to make suggestions. This priming procedure was
      compared with the more usual procedure of "welcoming" attendance and suggestions.
      It was found that more suggestions were made when attendance was required, rather
      than optional. This increase occurred during a group as well as a private
      meeting. An attempt was then made to analyze the probable reinforcer for the
      suggestions by experimentally varying the percentage of suggestions followed.
      Different staff members served as the discriminative stimuli within a multiple
      schedule. It was found that the number of suggestions was a direct function of
      the percentage followed. These results demonstrate the effectiveness of the
      priming procedure as an adjunct to reinforcement procedures for increasing
      desired behaviors of mental patients. Few suggestions were made when
      reinforcement or priming were used alone.

PMID- 16795198
TI  - A token reinforcement program in a public school: a replication and systematic
      analysis.
AB  - A base rate of disruptive behavior was obtained for seven children in a second
      grade class of 21 children. Rules, Educational Structure, and Praising
      Appropriate Behavior while Ignoring Disruptive Behavior were introduced
      successively; none of these procedures consistently reduced disruptive behavior.
      However, a combination of Rules, Educational Structure, and Praise and Ignoring
      nearly eliminated disruptive behavior of one child. When the Token Reinforcement
      Program was introduced, the frequency of disruptive behavior declined in five of
      the six remaining children. Withdrawal of the Token Reinforcement Program
      increased disruptive behavior in these five children, and reinstatement of the
      Token Reinforcement Program reduced disruptive behavior in four of these five.
      Follow-up data indicated that the teacher was able to transfer control from the
      token and back-up reinforcers to the reinforcers existing within the educational
      setting, such as stars and occasional pieces of candy. Improvements in academic
      achievement during the year may have been related to the Token Program, and
      attendance records appeared to be enhanced during the Token phases. The Token
      Program was utilized only in the afternoon, and the data did not indicate any
      generalization of appropriate behavior from the afternoon to the morning.

PMID- 16795199
TI  - Modification of severe disruptive and aggressive behavior using brief timeout and
      reinforcement procedures.
AB  - Brief timeout for disruptive and aggressive behaviors and reinforcement for
      appropriate behaviors were used with two retarded patients in a state hospital
      ward setting. The procedures reduced loud vocal behavior in one patient and
      aggressive behavior in another to near-zero levels when first applied. The
      behaviors returned to previous levels when the procedures were removed and were
      again greatly reduced when timeout and reinforcement were reapplied. The results
      were significant because the behavior problems were severe and long-standing and
      the procedures were instituted without greatly disturbing normal ward routine.

PMID- 16795200
TI  - Behavioral engineering: the use of response priming to improve prescribed self
      medication.
AB  - A major problem in outpatient treatment has been the extreme irregularity with
      which patients use medication prescribed for them. As a new approach to resolving
      this problem, a portable operant apparatus was developed based on response
      priming and escape reinforcement. The apparatus sounded a tone at the time that a
      pill was to be taken. When the user turned a knob to terminate the tone, the
      apparatus delivered the pill into the user's hand. The apparatus was evaluated
      with six normal adults using a medically inert pill. A greater proportion of the
      pills were taken by each subject when using the special apparatus as compared
      with the use of a portable alarm timer or the usual wristwatch. These results
      demonstrate a new approach for increasing the regularity of self-administration
      of medicines.

PMID- 16795201
TI  - Switching requirements in a Head Start classroom.
AB  - Two experiments were conducted by the mothers of the children in a Head Start
      classroom. Both examined the effects of a switching task on the frequency with
      which children moved from one activity area of the classroom to another. The
      results indicated that the rate at which the children changed activities could be
      adjusted by varying the difficulty or magnitude of the switching task and that
      the task itself could be used to introduce academic subjects which would be
      poorly attended if initially presented in an activity area.

PMID- 16795202
TI  - Academic response rate as a function of teacher- and self-imposed contingencies.
AB  - The purpose of this study was to assess the effects of the contingency manager
      (teacher or pupil) on a pupil's academic response rate. The results of two such
      experiments disclosed that higher academic rates occurred when the pupil arranged
      the contingency requirements than when the teacher specified them. A third study
      manipulated only reinforcement magnitude to ascertain whether amount of
      reinforcement had interacted with pupil-specified contingencies to produce the
      increase in academic response rate. The latter findings revealed that the
      contingency manager, not reinforcement magnitude, accounted for this subject's
      gain in performance.

PMID- 16795203
TI  - A functional analysis of receptive language and productive speech: acquisition of
      the plural morpheme.
AB  - Operant conditioning procedures were applied to two retardates to establish
      receptive auditory plurals: correct pointing to single or paired objects was
      reinforced after hearing singular or plural labels. This training proceeded until
      an errorless (generative) criterion of correct performance was achieved.
      Unreinforced probes measuring expressive use of singulars and plurals were
      interspersed in this receptive training. Neither subject generalized from this
      receptive training to expressive plurals, in that each used singulars when
      labeling pairs. Then, both subjects were directly trained in conventional
      expressive plurals to an errorless (generative) criterion. The previous design
      was then repeated, but the receptive repertoire was reversed: pointing at pairs
      in response to singular labels was reinforced, and vice-versa. Unreinforced
      probes of expressive plural usage again showed its independence of the current
      receptive repertoire in that conventional (unreversed) plural usage was
      displayed. Thus, the independence of the expressive repertoire (even when
      unreinforced) from the reinforced patterns of the receptive repertoire was
      demonstrated.

PMID- 16795204
TI  - Visually discriminated behavior in a "blind" adolescent retardate.
AB  - A 16-yr-old retarded male, diagnosed organically blind and treated by those
      around him as a blind person, was given practice in discriminating visual
      stimuli. After training, he responded with significantly better than chance
      accuracy in a choice situation in which stimuli were as small as 18 pt Futura
      Medium type. In addition, he was trained to look at the experimenter's eyes when
      instructed to do so. Control procedures revealed that it was the reinforcement
      contingency that functioned to establish and maintain eye contact. Eye contact
      with the experimenter generalized in a limited way to situations in which this
      behavior was not reinforced, though not to a neutral individual. When the boy was
      required to use visual cues to help himself in a cafeteria line, he soon emitted
      the necessary behaviors, where formerly he had been assisted by others.
      Resumption of assistance markedly decreased self-help, suggesting that continued
      use of any newly learned skills would depend on the response of the individuals
      in his environment. The boy also learned eating behavior that appeared to require
      the use of visual cues.

PMID- 16795205
TI  - An inexpensive token.

PMID- 16795206
TI  - Differential effects of token reinforcement on instruction-following behavior in
      retarded students instructed as a group.
AB  - This study was addressed to the problem of applying behavior modification
      techniques on a group basis to a class of retarded students with "attentional
      deficits". Seven boys, age 8 to 15 yr, characterized as showing severe
      "attentional" problems or disruptive behavior in their respective classrooms,
      participated daily for 30-min sessions in a special class over a 1.5-month
      period. In each session, verbal instructions were given to the class as a whole.
      In control sessions, each appropriate instruction-following response by a child
      produced praise for that child. In experimental sessions, appropriate responses
      also produced tokens exchangeable for tangible reinforcers after the session.
      Token reinforcement differentially maintained instruction-following behavior in
      four children while one responded appropriately to most instructions and a second
      improved continuously during the study. While the data suggest that the present
      approach can be successfully applied to the alteration of instruction-following
      behavior in retarded children, its major contribution may be that of providing
      objective quantitative information about such behavior.

PMID- 16795207
TI  - Free-time as a reinforcer in the management of classroom behavior.
AB  - Six subjects, comprising one class at a school for the deaf, were given
      reinforcement consisting of time free from school work for remaining seated in
      the classroom. As a result, the frequency of leaving their chairs was sharply
      reduced. A second procedure presented free-time not contingent on remaining
      seated. Little change was seen in the already lowered response rate. An extension
      of the time required to be seated with corresponding reduction in the number of
      daily free-time periods did not reduce the effectiveness of the procedure. A one
      day observation after six weeks indicated that the procedure was still effective.
      A one-day contingency reversal, requiring subjects to leave their chairs at least
      once during each seated period in order to receive free-time, substantially
      raised the frequency of out-of-seat responses.

PMID- 16795208
TI  - Good behavior game: effects of individual contingencies for group consequences on
      disruptive behavior in a classroom.
AB  - Out-of-seat and talking-out behaviors were studied in a regular fourth-grade
      class that included several "problem children". After baseline rates of the
      inappropriate behaviors were obtained, the class was divided into two teams "to
      play a game". Each out-of-seat and talking-out response by an individual child
      resulted in a mark being placed on the chalkboard, which meant a possible loss of
      privileges by all members of the student's team. In this manner a contingency was
      arranged for the inappropriate behavior of each child while the consequence
      (possible loss of privileges) of the child's behavior was shared by all members
      of this team as a group. The privileges were events which are available in almost
      every classroom, such as extra recess, first to line up for lunch, time for
      special projects, stars and name tags, as well as winning the game. The
      individual contingencies for the group consequences were successfully applied
      first during math period and then during reading period. The experimental
      analysis involved elements of both reversal and multiple baseline designs.

PMID- 16795209
TI  - A self-paced programmed undergraduate course in the experimental analysis of
      behavior.
AB  - A method of programming a variety of assignments in a course was described. The
      instructions to students, the course assignments, and the grading system were
      presented in detail. The rate at which students performed the activities was
      examined. Different students began working at different times during the
      semester, but once a student began to complete assignments he continued to work
      at a rate comparable to all other students. No students stopped working after
      once beginning to work. The majority of the students liked the course despite
      being overworked. Several changes in the method were suggested based on the data
      from this course.

PMID- 16795210
TI  - Vibration as a reinforcer with a profoundly retarded child.
AB  - Data are presented which indicate that lever-pressing behavior of a profoundly
      retarded child could be reinforced by the contingent application of vibratory
      stimulation for each response. With vibration available 24 hr per day, no
      decrement in daily rate of responding for vibration was seen over a three-week
      period. Suggestions are made for further use of this finding in working with the
      profoundly retarded.

PMID- 16795211
TI  - Reinforcing capabilities of television distortion.
AB  - The effectiveness of television distortion as a negative reinforcer was analyzed.
      Contingency arrangements involving television distortion were found to be capable
      of (a) accelerating the work rate of a naive, mildly retarded subject on a
      simulated production-line task involving card-sorting, and (b) reducing gross
      hyperactivity of a mildly retarded subject. An escape-avoidance contingency was
      arranged for the production-line behavior of the first subject and a punishment
      contingency for the hyperactive behavior of the second subject. Television
      distortion appears to be an effective and practical negative reinforcer for use
      in behavior modification.

PMID- 16795212
TI  - Contingency management in an introductory psychology course produces better
      learning.
AB  - For the contingency management techniques first devised by Keller (1966, 1968) to
      become a widely accepted teaching method, it is necessary that they be shown (1)
      to be applicable to general subject matter and (2) to be superior to traditional
      lecture methods. The present study demonstrated (1) by successfully teaching the
      material from a standard psychology text. The superiority of contingency
      management was established by direct comparison of final examination scores from
      comparable groups taught the same subject matter by either Keller's method or
      traditional methods. Students taught by Keller's method also rated the course
      more favorably.

PMID- 16795213
TI  - An elementary student as a behavioral engineer.
AB  - Four first-grade public school students exhibited non-study behaviors during a
      period when all children were to study individually. A fifth-grade student
      modified the maladaptive behaviors of the four first-grade students. Lights on
      the four students' desks, which were associated with opportunity for
      reinforcement, rapidly brought study behavior under stimulus control.
      Differential reinforcement of other behaviors dramatically decreased studying.
      Reinforcement was reinstituted and studying returned to a high and stable rate.
      Surreptitious post-experimental observation using closed-circuit TV indicated
      that the behavioral changes effected during the experimental phases were
      partially maintained by the regular classroom environment. A replication of the
      baseline phase with the observer in the classroom produced an increase in the
      rate of study behavior, indicating that the observer's presence acted as a
      discriminative stimulus for studying. An additional contingency requiring
      improved academic behavior was imposed before the fifth grader was given the
      opportunity to engage in the behavior modification experiment.

PMID- 16795214
TI  - Instructional control of an autonomic sexual response.
AB  - Four of seven human male subjects developed full penile erections when exposed to
      erotically stimulating motion pictures. Changes in penile size were detected by a
      mercury strain gauge transducer and automatically recorded on a continuous paper
      record. When instructed to inhibit penile erection in the presence of such
      effective stimulus films, every subject was able to reduce his erection by at
      least 50%. This inhibition was apparent as long as the instructions were in
      effect; when the instructions were removed and the film reshown, the erection
      returned almost to its maximum state. This was true whether the films were
      presented as few as three or as many as nine times in succession. When instructed
      to develop an erection in the absence of a film, every subject was able to do so,
      each reaching a peak of about 30% of his maximum. Such erections had longer
      latencies to the peak produced and lower maximum levels than those elicited by a
      film.

PMID- 16795215
TI  - Manipulation of self-destruction in three retarded children.
AB  - The study attempted to isolate some of the environmental conditions that
      controlled the self-destructive behavior of three severely retarded and psychotic
      children. In the extinction study subjects were placed in a room where they were
      allowed to hurt themselves, isolated from interpersonal contact. They eventually
      ceased to hurt themselves in that situation, the rate of self-destruction falling
      gradually over successive days. In the punishment study, subjects were
      administered painful electric shock contingent on the self-destructive behavior.
      (1) The self-destructive behavior was immediately suppressed. (2) The behavior
      recurred when shock was removed. (3) The suppression was selective, both across
      physical locales and interpersonal situations, as a function of the presence of
      shock. (4) Generalized effects on other, non-shock behaviors, appeared in a
      clinically desirable direction. Finally, a study was reported where self
      destructive behavior increased when certain social attentions were given
      contingent upon that behavior.

PMID- 16795216
TI  - Oppositional children: a quest for parental reinforcement control.
AB  - The present study attempted to examine changes in parental reinforcement value as
      a function of parental use of timeout and differential attention. Subjects were
      two children classified by their parents as highly oppositional to parental
      requests or commands. Results showed that the children's oppositional behavior
      varied predictably with the presence and absence of parental use of timeout and
      differential attention. As expected, parental reinforcement value for the
      children was higher during treatment periods than during baseline periods.

PMID- 16795217
TI  - Effects of group contingent events upon classroom noise.
AB  - The first study investigated a group control procedure for suppression of
      excessive sound-intensity levels in a regular public school classroom.
      Reinforcement consisted of a 2-min addition to the class gym period and a 2-min
      break after maintenance of an unbroken 10-min quiet period as monitored on a
      decibel meter. Transgressions of the sound limit (42 decibels) resulted in a
      delay of reinforcement by the resetting of the timer to the full 10-min interval.
      The results indicated that these procedures were highly effective in suppression
      and control of sound intensities. The second experiment utilized a similar
      procedure coupled with a procedure of eliminating out-of-seat behavior.
      Experiment III studied the effects of Exp. II procedures on a single student's
      out-of-seat behavior rate. All procedures were found effective.

PMID- 16795218
TI  - Behavior modification with culturally deprived school children: two case studies.
AB  - Techniques of behavior modification were employed with two second-grade Negro
      girls in a demonstration school for culturally deprived children to increase the
      girls' appropriate classroom behaviors. A classification system that provided for
      continuous categorization of behavior was used to code the children's behavior in
      two classroom situations. Data were also taken on the type, duration, and
      frequency of the teachers' verbal interactions. The study included four
      conditions: Baseline, Modification I, Postmodification, and Modification II. The
      treatment variable was positive social reinforcement-attention and approval
      contingent upon desirable classroom behaviors-which was presented, withheld, or
      withdrawn (timeout from social reinforcement). Withholding of social
      reinforcement was contingent upon inappropriate attention-getting behaviors.
      Timeout from social reinforcement was contingent upon behaviors classified as
      aggressive and resistive. After 25 days of Modification I, desirable behavior
      increased markedly for each girl. The teachers were then asked to return to their
      Baseline level of performance. The resultant behaviors demonstrated that for one
      girl, behavior was still primarily under the control of the treatment
      contingencies. For the second child, many desirable behaviors that had increased
      in frequency during Modification I remained high, but inappropriate behaviors
      increased. When treatment was reinstated, the amount of time spent in desirable
      behaviors increased and remained high for both girls. Three checks during the
      three months following data collection showed that these behaviors continued to
      remain high.

PMID- 16795219
TI  - Contingency management of toothbrushing behavior in a summer camp for children.
AB  - The control of toothbrushing behavior by contingency management was studied with
      eight, 10 to 12-yr-old boys at a summer camp for children. This behavior occurred
      infrequently during baseline conditions with and without verbal instructions to
      the subjects to brush their teeth. Toothbrushing behavior was maintained at a
      high level when the behavior was required as a prerequisite for the opportunity
      to swim (contingency management). When, after 22 days, the contingency
      arrangement between toothbrushing and swimming was terminated, toothbrushing
      behavior returned to a low level.

PMID- 16795220
TI  - Application of timeout from positive reinforcement for increasing the efficiency
      of speech training.
AB  - Language training procedures, which involved positive reinforcement for verbal
      imitation, were applied to increase the appropriate verbal behavior of an almost
      non-verbal, brain damaged, 5-yr-old boy. Two experiments assessed the
      effectiveness of timeout from positive reinforcement as a training procedure
      viewed as having potential punishing and negatively reinforcing functions. In
      both experiments, timein, termination of timeout and resumption of training, was
      arranged to have reinforcing properties in that it presented an opportunity to
      receive positive reinforcers. In Exp. I, the procedure consisted of temporarily
      halting language training (timeout) following verbal jargon and resuming it
      (timein) contingent upon the boy sitting quietly in his chair for approximately
      30 sec. The jargon declined to almost zero for an extended period each time the
      procedure was employed. In Exp. II, the procedure consisted of halting language
      training (timeout) after emission of undesired verbal responses which previously
      had been reinforced as the desired approximation to the target verbal behavior.
      Resumption of training (timein) was made contingent upon the emission of the then
      desired approximation of the target verbal behavior. In each experiment, the
      contingent timeout and timein of the language training that involved positive
      reinforcement effectively reduced the undesired and increased the desired
      responses.

PMID- 16795221
TI  - An information system for measuring patient behavior and its use by staff.
AB  - A behavioral measurement system was designed around a point economy for a
      psychiatric ward of delinquent patients. The characteristics of the system were:
      (1) the records of points earned for appropriate patient behavior formed the
      primary data. (2) After the points were recorded in a data matrix, graphs were
      prepared to show the behavior of individual patients, the participation of the
      patient group in the various ward activities, and an overall index of ward
      operation. (3) Several techniques were devised for reviewing the graphs so that
      the ward staff could evaluate the success of their procedures over substantial
      time periods.

PMID- 16795222
TI  - Contingency contracting with school problems.
AB  - Contingency contracting procedures used in managing problems with school-age
      children involved analyzing teacher and/or parental reports of behavior problem
      situations, isolating the most probable contingencies then in effect, the range
      of reinforcers presently available, and the ways in which they were obtained. The
      authors prepared written contracts delineating remediative changes in
      reinforcement contingencies. These contracts specified ways in which the child
      could obtain existing individualized reinforcers contingent upon approximations
      to desired appropriate behaviors chosen as incompatible with the referral problem
      behaviors. Contract procedures were administered by the natural contingency
      managers, parents and/or teachers, who kept daily records of contracted behaviors
      and reinforcers. These records were sent to the authors and provided feedback on
      the progress of the case. Initial results of this procedure have been
      sufficiently encouraging to warrant recommending an experimental analysis of
      contingency contracting as a clinical method.

PMID- 16795223
TI  - An inexpensive method for making data records of complex behaviors.

PMID- 16795224
TI  - Behavioral engineering: stuttering as a function of stimulus duration during
      speech synchronization.
AB  - Past studies have shown that stuttering is eliminated when speech is synchronized
      with a metronomic beat, but the speech sounds artificial. The present study
      investigated the effect of increasing the duration of these individual stimulus
      beats with the stimulus-off period constant at 1 sec. When subjects were
      instructed to speak during the stimulus-on period, stuttering was an inverse
      function of stimulus duration, indicating that the known metronome effect on
      stuttering is one point on a continuum of effective rhythm procedures. The
      "naturalness" of speech increased as the stimulus duration increased up to
      durations of about 2 sec, and then decreased. At optimal values, stuttering was
      greatly reduced and naturalness and rapidity of speech were retained. These
      optimal values effectively controlled stuttering in a field test that used two
      types of specially designed portable instruments, one of which produced a tactual
      stimulus and the other an auditory stimulus.

PMID- 16795225
TI  - An instrument for producing deep muscle relaxation by means of analog information
      feedback.
AB  - An instrument that assists subjects in attaining deep muscle relaxation by means
      of analog information feedback is described. Subjects hear a tone with a pitch
      proportional to the electromyographic activity in a given muscle group. Results
      showed that subjects receiving this type of analog feedback reached deeper levels
      of muscle relaxation than those receiving either no feedback or irrelevant
      feedback. The basic method employed-electronic detection, immediate information
      feedback, and systematic shaping of responses-would seem potentially applicable
      to a variety of physiological events, and might be useful both in behavior
      therapy and in certain psychosomatic disorders.

PMID- 16795226
TI  - Setting generality: some specific and general effects of child behavior therapy.
AB  - The present study attempted to assess experimentally, functional relationships
      between home and school settings. Two children, both considered deviant in their
      homes and in their schools, were observed in both settings. The observations
      revealed that the children's deviant behaviors at home were quite similar to
      their deviant behaviors at school. Contingency operations were then performed in
      the children's homes. Results showed that the children's behavior changed
      predictably in the homes and remained at baseline level in school.

PMID- 16795227
TI  - Operant reinforcement of prayer.

PMID- 16795228
TI  - Effects of mixed reinforcement contingencies on adults' control of children's
      behavior.
AB  - Two severely retarded boys, each a member of a different play group, experienced
      three regimes of reinforcement from adults [contingent, noncontingent, and mixed
      (contingent and noncontingent)]. The agent of contingent reinforcement acquired
      stimulus control of the subjects' behavior; the noncontingent agent did not. The
      agent of the mixed schedule of reinforcement did not gain control, but aspects of
      his behavior came to function as cues. The mixed adult's withholding
      reinforcement in the absence of the target behavior (cooperative play) evoked
      cooperative play, whereas his presenting free reinforcement resulted in the
      subjects' remaining in their inactive, baseline positions.

PMID- 16795229
TI  - Performance determined instruction for training in remedial reading.
AB  - A system called Performance Determined Instruction (PDI) is presented as a
      methodological tactic for training in remedial reading. The system incorporates
      aspects of binary logic, instrumental conditioning, and programmed instruction.
      Results suggest that PDI is a high-precision instructional procedure effective in
      obtaining desired changes in reading-task performance.

PMID- 16795230
TI  - Rapid computation and pupil self-recording of performance data.

PMID- 16795231
TI  - Suppression of normal speech disfluencies through response cost.
AB  - The speech disfluencies of five normal-speaking college students were modified in
      a series of 10 to 17 sessions by means of response cost. During Point-loss, each
      disfluency (repetition or interjection of a sound, syllable, word, etc.) resulted
      in the loss of a penny, as indicated on a screen in front of the subject.
      Disfluencies were suppressed and kept at very low levels for four of the subjects
      during the punishment procedures, and there was general resistance to extinction.
      Even though points were subtracted only during speech, there was a tendency for
      disfluencies to decrease, though not as markedly, during reading probes as well.

PMID- 16795232
TI  - The application of operant conditioning techniques in a secondary school
      classroom.
AB  - The effects of teacher praise and disapproval on two target behaviors,
      inappropriate talking and turning around, were investigated in a high school
      English class of 25 students. The contingencies were applied to all students in
      the experimental class utilizing a multiple baseline experimental design in which
      the contingencies were aimed first at decreasing inappropriate talking behavior
      and then at decreasing inappropriate turning behavior. Observations were made of
      both student and teacher behavior. The results demonstrated that the combination
      of disapproval for the target behaviors and praise for appropriate, incompatible
      behaviors substantially reduced the incidence of the target behaviors in the
      experimental class. Observations of these behaviors in a control class of 26
      students taught by the same teacher revealed no particular changes. The findings
      emphasize the importance of teacher-supplied social contingencies at the
      secondary school level.

PMID- 16795233
TI  - Feedback to attendants as a reinforcer for applying operant techniques.
AB  - After varying lengths of baseline, initiation of a feedback system increased the
      daily use of operant training methods by non-professional hall personnel in a
      state institution for retarded children.

PMID- 16795234
TI  - The control of "classroom attention": a group contingency for complex behavior.
AB  - Cumulative time measures of classroom attention, as delineated by the teacher,
      were taken of four elementary classes (kindergarten, third, fifth, and sixth
      grades) and of 16 randomly chosen students in these same classes. Each class of
      students was viewed as an individual responding organism. Base rates showed
      considerable variability. Explicit instructions alone concerning student
      attention produced temporary increase for some students and for some grades.
      Adding group contingencies (i.e., contingencies dependent on the attention of
      every student in the class) and token-mediated reinforcement to class achievement
      of a gradually increasing attention criterion raised group measures to a
      consistent 70 to 85% level of time attending to task as instructed, and raised
      individual student measures to a stable 90 to 100% level. Reversals and other
      data indicate that the elementary teacher can, by herself and with little effort,
      maximize what she considers the "paying-attention behavior" of all her students
      by her less-than-precise measure and consequation of the attention of the class
      as a whole.

PMID- 16795235
TI  - Some experiments on reinforcement principles within a psychiatric ward for
      delinquent soldiers.
AB  - Several experiments exploring the effects of certain behavioral procedures were
      performed on a psychiatric ward for delinquent soldiers. Within the context of a
      point economy, the behavioral procedures were examined for their applicability to
      this patient group in a hospital-ward setting. The following procedures were
      studied: (1) use of points as consequences for specific behaviors compared with
      demonstration of "model" behavior by a ward officer; (2) punishment by a point
      fine to control undesired behavior; (3) use of a chaining-type reinforcement
      contingency to increase desired behavior; (4) differential reinforcement of the
      individual versus the group to increase the frequency of a verbal performance;
      and (5) reinforcement of reports of personal problems versus impersonal problems.

PMID- 16795236
TI  - An analysis of generalized imitation.
AB  - An experimenter presented English words to three intermediate-level children and
      reinforced accurate imitation of these words. The experimenter also presented
      novel Spanish words, but the imitation of these words was never experimentally
      reinforced. One subject quickly ceased performing non-reinforced imitative
      responses. The other two subjects were exposed to a series of conditions designed
      to facilitate discrimination. Upon observing the first subject for one session
      they immediately ceased imitating Spanish demonstrations. For all three subjects,
      when reinforcement was delivered for responses other than imitation, all
      imitative responses eventually ceased. When reinforcement was reintroduced for
      English imitations there was an immediate resumption of such responses to their
      previous 100% level. The occurrence of non-reinforced imitations in this and
      previous studies was discussed as being a function of one or combination of four
      variables: (1) similarity acquiring conditioned reinforcing properties, or (2)
      instructional, (3) coincidental, or (4) conditional stimulus generalization.

PMID- 16795237
TI  - Management of chronic psychiatric patients by a token reinforcement system.
AB  - A token reinforcement system for the reduction of institutionalized behavior in a
      chronic psychiatric ward is described. Quantitative assessments were made of the
      effects of the system on five types of positively reinforced behavior, two types
      of unreinforced behavior, and two types of fined behavior. To assess whether
      these effects were a function of the token procedures, three experiments were
      carried out, the first removing tokens for a brief period, the second making
      tokens non-contingent on behavior, and the third removing fines in one area while
      maintaining them in another. The token procedures were found to be the source of
      the observed improvements.

PMID- 16795238
TI  - Design and evaluation of a programmed course in introductory psychology.
AB  - The design of a programmed course in introductory psychology, utilizing an
      interview procedure, is described. The performance of students in this course was
      compared with that of students covering the same subject matter but taught in a
      more conventional manner. Students in the experimental course scored
      significantly higher on objective and essay final examinations and rated the
      course more positively.

PMID- 16795239
TI  - Reinforcing self-help group activities of welfare recipients.
AB  - The attendance rates of welfare recipients at self-help group meetings was
      compared when supplementary reinforcement was given for attending and when it was
      not. Reinforcers included donated items, such as clothing and household goods,
      and information about welfare services. It was found that the attendance at
      meetings averaged three recipients per meeting without reinforcement and 15
      recipients per meeting with reinforcement. There was evidence that attendance was
      associated with participation in other self-help activities. It was concluded
      that practical forms of reinforcement can be found to maintain the participation
      of severely disadvantaged populations in self-help groups.

PMID- 16795240
TI  - What psychology has to offer education-now.

PMID- 16795241
TI  - A mechanical strain gauge for recording penile circumference change.

PMID- 16795242
TI  - Self-injurious behavior: shaping "head banging" in monkeys.
AB  - Head-banging, a common phenomenon among the mentally retarded, was shaped,
      brought under stimulus control, extinguished, and re-established in two monkeys
      through reinforcement and discrimination procedures of operant conditioning. The
      behavior was stable and led to lacerations, a condition that qualifies head
      banging as self-injurious. The principles of the analysis of behavior used here
      may well be of value in the etiology and treatment of some human head-banging.

PMID- 16795243
TI  - The effects of teacher attention on following instructions in a kindergarten
      class.
AB  - A kindergarten class, composed of five girls ages 4.8 to 6 yr, participated in
      the study. In each of 20 daily sessions a sequence of 10 simple instructions was
      given to the class, In baseline sessions, the teacher did not interact with the
      students, other than to give instructions. During these sessions, the children
      followed the teacher's instructions 60% of the time. When the teacher began
      attending to each child if she followed an instruction, the mean percentage of
      instructions followed increased to 78%. Subsequently, the teacher again employed
      the baseline procedures and the percentage of instructions followed decreased to
      68.7%. When the teacher again provided attention dependent on the children's
      following the instructions, the percentage of instructions followed increased to
      83.7%. The results are consistent with research that has treated instructions as
      discriminative stimuli. The general findings are that consequences of instructed
      behavior determine the extent to which the instructions are followed.

PMID- 16795244
TI  - Classroom applications of self-determined reinforcement.
AB  - Self-determined, experimenter-determined, and chance-determined token
      reinforcement treatments were compared with a no-token treatment, in terms of
      effect on the learning of history and geography material in the classroom. Each
      treatment was assigned to one of four heterogeneous classes of Grade nine girls.
      An initial baseline period preceded the differential reinforcement period, and a
      token withdrawal period followed. Subsequently, the self-determined treatment was
      employed in all three token reinforcement classes, before a final baseline period
      occurred. Findings included a similarity of initial baseline performance for all
      classes, an equal superiority of self-determined and experimenter-determined
      treatments to chance-determined and no-token treatments, and significant
      improvement from initial baseline to final baseline for self-determined and
      experimenter-determined treatments, but not chance-determined and no-token
      treatments. Differential token reinforcement experience was found to influence
      subsequent rate of self-determined token reinforcement.

PMID- 16795245
TI  - Development of social responses in two severely retarded children.
AB  - The effect of reinforcement dependent on the social responses of two severely
      retarded withdrawn children was investigated. During 30 training sessions (30 min
      each) food and praise were administered dependent upon the children's mutual
      participation in a ball-rolling and block-passing task. Both children showed a
      progressive increase in social interaction in a non-training situation during
      this reinforcement period. After the reinforcement procedures were removed,
      social behavior decreased markedly. Response generalization to children not
      involved in training occurred.

PMID- 16795246
TI  - Operant training and generalization of a verbal response form in a speech
      deficient child.
AB  - A subject who spoke essentially in "telegraphic" English, leaving out most
      articles and auxiliary verbs, was trained to use a particular sentence form that
      included the articles and verbs to describe a set of standardized pictures. The
      subject used the trained sentence form to describe the trained pictures, and in
      addition, use of the sentence form generalized to sets of untrained and novel
      stimuli. When the trained sentence form was changed, the subject used the new
      form to describe both training and generalization stimuli. When the original
      correct form of response was retrained, the subject once again used the trained
      sentence form to respond to both training and generalization trials.

PMID- 16795247
TI  - Modification of extreme social isolation by contingent social reinforcement.
AB  - Two socially isolated patients were placed on a program where social
      reinforcement from staff members was made dependent on social interaction with
      other patients or staff members. This procedure was imposed in a setting where
      only limited control was possible. The level of social interaction and a
      concomitant alternate behavior in each patient was increased when the contingency
      for social reinforcement was imposed. The study provides another example of the
      efficacy of social reinforcement where there is little control over other
      reinforcers. Implications for use of similar procedures to increase
      generalization in the community are discussed.

PMID- 16795248
TI  - The experimental modification of teacher attending behavior.
AB  - A method of observing and modifying teacher attention to appropriate child
      responses in preschool classrooms was developed. Two teachers with no formal
      training in reinforcement principles were observed for a baseline of eight days.
      Teacher A, who displayed a lower baseline rate of attending to appropriate child
      responses, was trained first. Teacher B was simply observed during the first part
      of the training condition for Teacher A. During training, A received feedback
      which included definitions of appropriate child responses, her frequency of
      attending to appropriate child responses, her total percentage of attending to
      appropriate child responses, and her frequency of failing to attend to
      appropriate child responses. Teacher B was then trained in a similar way. Both
      teachers showed an increase in attending to appropriate child responses
      subsequent to the onset of experimental feedback.

PMID- 16795249
TI  - Improvement of retardates' mealtime behaviors by timeout procedures using
      multiple baseline techniques.
AB  - Undesirable mealtime behaviors of a hospital cottage of retardates were reduced
      by contingent timeout procedures applied by ward personnel successively to one
      undesirable behavior after another, in a multiple baseline design. In some cases
      the timeout procedure was to remove the subject from the room until the meal was
      finished; in other cases (depending on the health of the child and the initial
      rate of the behavior to be reduced), timeout consisted of a 15-sec removal of the
      child's meal tray. Undesirable behaviors were defined as stealing, using fingers
      inappropriately, messy use of utensils, and pigging (eating directly with mouth
      or eating spilled food). Timeout was applied to these behaviors in that order,
      and in each case led to a marked and useful reduction in the behavior throughout
      the group. As these undesirable behaviors were reduced, more appropriate mealtime
      behaviors emerged: as inappropriate use of fingers declined (under contingent
      timeout), messy utensil behavior increased; later, as messy utensil behavior
      declined (under contingent timeout), a defined category of neat utensil behavior
      increased. Weights of the subjects were monitored steadily throughout the study
      and showed essentially no change.

PMID- 16795250
TI  - Application of delayed reinforcement procedures to the behavior of an elementary
      school child.
AB  - Delayed reinforcement techniques were applied, in a multiple baseline
      experimental design, to modify the behavior of a mildly maladjusted sixth-grade
      child. The following behaviors were chosen for modification: face-touching,
      posture, and voice-loudness. Videotape recordings were made of the subject's
      behavior during mathematics and spelling periods each day. The recordings from
      the mathematics period was shown to her after school, and consequences for
      behavior exhibited during mathematics were dispensed during the after-school
      viewing. This delayed reinforcement procedure produced the desired behavior
      changes during the mathematics period. Tapes from the spelling period, which were
      taken without the child's knowledge, indicated that the behavior changes
      generalized to portions of the day other than the mathematics period.

PMID- 16795251
TI  - Reinforcement of visual attending in classrooms for deaf children.
AB  - The efficacy of immediate tangible reinforcement in increasing appropriate visual
      attending for entire classes of deaf children was examined. The subjects were
      three classes (seven children each) in a residential school for the deaf. Boxes
      were installed on each child's desk, with lights that were flashed immediately
      contingent upon 10 sec of visual attending. Light flashes were backed up by M &
      M's, cereal bits, or tokens. In two of the classes, extinction sessions were also
      scheduled. For all classes, the reinforcement procedure increased visual
      attending by 50% or more, maintaining it at rates above 82%. Withdrawal of
      tangibles decreased attending back to baseline levels. The results support
      analysis of attending as operant behavior and demonstrate the applicability of
      reinforcement procedures in modifying these behaviors for young deaf children in
      a classroom setting.

PMID- 16795252
TI  - The social control of generalized imitation.
AB  - Instructions, discrimination procedures, and sources of reinforcement were
      manipulated in order to determine the bases for the maintained "non-reinforced"
      imitations observed in generalized imitation research. Six girls received
      imitation training from two experimenters. One experimenter modelled only
      reinforced responses; the other modelled only non-reinforced responses. The
      children imitated all responses when no reinforced alternative was available,
      even though results of choice procedures and special instructions clearly
      demonstrated that they discriminated reinforced from non-reinforced responses.
      Instructions not to perform non-reinforced imitations immediately eliminated
      these behaviors. It is suggested that social setting events may be largely
      responsible for generalized imitation.

PMID- 16795253
TI  - The effects of token procedures on a teacher's social contacts with her students.
AB  - The effects of a token system on a teacher's rate of social contacts with her
      students were investigated in a public school kindergarten. A group of six
      children were observed daily during a 20-min handwriting lesson. The children
      were divided into two groups (A and B) of three children each. Five conditions
      were imposed sequentially: (1) baseline without tokens, (2) contingent tokens for
      Group A, noncontingent tokens for Group B, (3) contingent tokens for Group B,
      noncontingent tokens for Group A, (4) reinstatement of condition 2, and (5)
      contingent tokens for both groups. It was consistently observed that the
      teacher's rate of social contact was higher with the children receiving the
      contingent tokens than with those who received noncontingent tokens.

PMID- 16795254
TI  - Contingency counseling by school personnel: an economical model of intervention.
AB  - An Attendance Counselor contacted adults (mediators) who controlled reinforcers
      for six chronic nonattenders (targets); agreements (deals) were made between
      mediators and targets that reinforcers would be provided, contingent on school
      attendance. Absence of the Attendance Counselor from school for a two-week period
      constituted a reversal condition, after which the "deals" were reinstituted.
      Results showed a significant increase over baseline in school attendance during
      the time in which deals were in effect. A second study involved 20 chronic
      nonattenders for whom deals were arranged as in Study One (contingency
      counseling), and 15 nonattenders provided more traditional attendance counseling
      (contact counseling). Contingency Counselors achieved results with the 20
      nonattenders similar to those achieved in Study One. An experienced Contact
      Counselor did not achieve improved school attendance among her group of 15
      nonattenders.

PMID- 16795255
TI  - A "paper money" token system as a recording aid in institutional settings.

PMID- 16795256
TI  - Emphasis as a prompt for verbal imitation.
AB  - Four- and five-yr-old disadvantaged children were read sentences composed of
      varying numbers of short phrases. The children were asked to repeat each
      sentence, but the accuracy of their imitations was not differentially reinforced.
      The teacher stressed (emphasized) certain words as she read each sentence. The
      proportion of words that were stressed was systematically varied. In general, the
      children imitated only parts of most sentences. Stress was effective in
      influencing which parts of a sentence the children would imitate, but only when
      relatively few words were stressed. Stressing a word increased the probability of
      a child's imitating that word (and, to a large extent, the entire phrase
      containing that word) as an inverse function of the proportion of the words that
      were stressed.

PMID- 16795257
TI  - Operant learning principles applied to teaching introductory statistics.
AB  - A grade of A was given in an introductory statistics course for meeting a set of
      contingencies that included no work outside of class (except by request), near
      perfect performance on exams following each unit of work in a programmed text,
      correction of all exam errors, self pacing of work, and the chance to finish the
      course early. A grade of incomplete was given otherwise. Correlations among
      performance measures failed to show any meaningful relationships between time
      taken to finish the course, errors made on exams, and errors made in the
      programmed text. Responses to a five-part questionnaire were overwhelmingly
      favorable to the course, but did not vary as a function of grade point average,
      time taken to finish the course, or number of errors made on exams. The uniformly
      high level of performance, the students' lack of interest in social contact with
      the instructor during class, and the absence of drop-outs are all attributed to
      the contingencies employed, chief among which, according to the instructor's
      judgment and student rankings, were self-pacing, frequent non-punitive exams and
      a guaranteed grade of A for near-perfect work at every stage.

PMID- 16795258
TI  - Effects of teacher attention on attending behavior of two boys at adjacent desks.
AB  - The effects of teacher attention on the attending behavior of two boys seated at
      adjacent desks were investigated. Baseline records were obtained of the
      appropriate attending behavior of two boys who were described as the most
      disruptive pupils in a second-grade classroom of a poverty area school. During
      the first experimental phase, the teacher systematically increased the amount of
      attention for appropriate attending in one of the pair, Edwin. This resulted in a
      dramatic increase in his attending rate and a lesser, though significant,
      increase in attending behavior of the second boy, Greg. During the second
      experimental phase, systematic attention for attending was instituted for Greg
      and was discontinued for Edwin. This resulted in further increases in attending
      by Greg and a reduction in attending by Edwin. A brief withdrawal of
      reinforcement for attending in both Greg and Edwin reduced attending levels for
      both. Following this reversal appropriate attending for both boys was
      systematically reinforced and attending returned to high levels.

PMID- 16795259
TI  - Generalization of aggressive behavior in adolescent delinquent boys.
AB  - The generalization of conditioned aggressive and nonaggressive responses in a
      group of six adolescent delinquent boys was investigated. Responses were
      reinforced in card games where a token reinforcement system with money as a back
      up rinforcer was used. Conditioning of responses was rapid. Generalization,
      measured in terms of frequency of physical contact, was tested in a group game
      for which no reinforcement was given. Generalization occurred during aggressive
      contingencies. During nonaggressive contingencies, responses did not return
      completely to the baseline level.

PMID- 16795261
TI  - The adaptation of commercially available radio control equipment to behavior
      therapy.

PMID- 16795260
TI  - The use of a token system in project Head Start.
AB  - The present experiment sought to develop a practical and effective method for
      teaching the beginning elements of hand-writing in a Head Start program. The
      method consisted of reinforcing responses to a writing program by giving the
      children access to a variety of activities normally available in the pre-school
      classroom. Tokens were presented for correct responses. The children then used
      the tokens to select reinforcers, such as snacks and access to a variety of play
      activities. In an experimental evaluation of the token system, it was found that
      responding was maintained as long as access to the reinforcing activities was
      contingent upon responding. When reinforcement was no longer contingent upon
      responding, virtually no responding occurred. Informal observations suggested
      that the token system had several unanticipated effects: the children's
      vocabulary and ability to understand instructions improved; a favorable attitude
      toward school developed; and their ability to play cooperatively with other
      children increased. It was concluded that the token system is a practical and
      effective method for teaching beginning writing skills and that it has other
      desirable, if unanticipated, effects.

PMID- 16795262
TI  - Home-based reinforcement and the modification of pre-delinquents' classroom
      behavior.
AB  - In Exp. I, five pre-delinquents from Achievement Place attended a special summer
      school math class where study behavior and rule violations were measured daily
      for each boy. The boys were required to take a "report card" for the teacher to
      mark. The teacher simply marked yes or no whether a boy had "studied the whole
      period" and "obeyed the class rules." All yeses earned privileges in the home
      that day but a no lost all the privileges. Using a reversal design, it was shown
      that privileges dispensed remotely could significantly improve classroom
      performance. In Exp. II and III, home-based reinforcement was also shown to be
      effective in improving the study behavior of two youths in public school
      classrooms. In addition, data from Exp. III suggest that the daily feedback and
      reinforcement may be faded without much loss in study behavior. Home-based
      reinforcement was demonstrated to be a very effective and practical classroom
      behavior modification technique.

PMID- 16795263
TI  - Behavioral engineering: control of posture by informational feedback.
AB  - The effects of informational feedback on a socially undesirable behavior were
      studied. The feedback was a mild vibrotactile stimulus and the response was
      slouching. When subjects slouched, a behavioral engineering apparatus provided
      vibrotactile stimulation to the shoulder. All subjects slouched less when
      stimulation was provided. A procedural control revealed that slouching will
      decrease because of the informational aspect of the stimulus consequence and not
      because of its aversive properties. When the subjects were instructed to slouch,
      the effects of feedback were reversed: feedback increased, rather than decreased,
      slouching. These results indicate that the effect of feedback for a response
      depends on the subject's motivation to perform that response. It is suggested
      that informational feedback could be used more widely as a therapeutic procedure
      to modify human behaviors, but only those behaviors that a patient is strongly
      motivated to change.

PMID- 16795264
TI  - The punishment of persistent vomiting: a case study.
AB  - In an attempt to control severe vomiting in a mentally retarded patient, shock
      was delivered after each stomach tension, a pre-vomiting response that consisted
      of an overt abdominal movement. Contingent shock resulted in an initial
      transitory increase followed by a decrease in rate of stomach tensions. There was
      a decrease in emitted vomitus, which resulted in a weight gain of the patient.

PMID- 16795265
TI  - Teachers and parents as researchers using multiple baseline designs.
AB  - Two teachers and a parent used three basic multiple baseline designs to
      investigate the effects of systematic reinforcement and punishment procedures in
      the classroom and at home. (1) A fifth-grade teacher concurrently measured the
      same behavior (tardiness) in three stimulus situations (after morning, noon, and
      afternoon recesses). Posting the names of pupils on a chart titled "Today's
      Patriots" was made contingent on being on time after the noon recess, then
      successively also the morning and afternoon recesses. Tardiness was reduced to
      near zero rates at the points where contingencies were applied. (2) A highschool
      teacher recorded the same behavior (daily French-quiz grades) of three students.
      She then successively applied the same consequences (staying after school for
      individual tutoring for D and F grades) for each student. At the points where the
      contingency was applied, D and F grades were eliminated. (3) A mother
      concurrently measured three different behaviors (clarinet practice, Campfire
      project work, reading) of her 10-yr-old daughter. She successively applied the
      same contingency (going to bed early) for less than 30 min spent engaged in one
      after another of the behaviors. Marked increases in the behaviors were observed
      at the points where the contingency was applied.

PMID- 16795266
TI  - A cueing device for the acceleration of the rate of positive interaction.

PMID- 16795267
TI  - The relative effects on math performance of single- versus multiple-ratio
      schedules: a case study.
AB  - This series of four experiments sought to assess the comparative effects of
      multiple- versus single-ratio schedules on a pupil's responding to mathematics
      materials. Experiment I, which alternated between single- and multiple-ratio
      contingencies, revealed that during the latter phase the subject responded at a
      higher rate. Similar findings were revealed by Exp. II. The third experiment,
      which manipulated frequency of reinforcement rather than multiple ratios,
      revealed that the alteration had a minimal effect on the subject's response rate.
      A final experiment, conducted to assess further the effects of multiple ratios,
      provided data similar to those of Exp. I and II.

PMID- 16795268
TI  - A universal behavior graph paper.

PMID- 16795269
TI  - Training generative verb usage by imitation and reinforcement procedures.
AB  - Three retarded children were trained, using imitation and reinforcement
      procedures, to produce past and present tense forms of verbs in response to
      verbal requests. Two types of experimental sessions were arranged: training
      sessions and probe sessions. During training sessions, a child was trained to
      produce one verb in both the past and the present tense. Then, in a probe
      session, the generalization of this training was tested by presenting to the
      child a series of untrained verbs interspersed with previously trained verbs.
      Responses to untrained verbs were never reinforced. Training sessions alternated
      with probe sessions throughout a multiple baseline design involving four classes
      of verb inflections as the baselines. The results showed that, as past and
      present tense forms of verbs within an inflectional class were trained, the
      children correctly produced past and present tense forms of untrained verbs
      within this class. When verbs from two or more classes were trained, the children
      correctly produced the verb tenses from each of these classes. Thus, the
      imitation and reinforcement procedures were effective in teaching generative use
      of verb inflections.

PMID- 16795270
TI  - The use of a credit card in a token economy.

PMID- 16795271
TI  - A conditioning technique applicable to elementary school classrooms.
AB  - A procedure was developed for use in a public school classroom where only one of
      the children needed treatment, sophisticated apparatus was not feasible,
      personnel were untrained in conditioning techniques, and where disruption had to
      be minimized. Candy reinforcers were contingent upon working behavior. The total
      candy earned in the session was divided equally among the class. Portable radio
      control apparatus was adopted to give feedback to the child when he was
      displaying the desired working behavior. An increase in working behavior and a
      decrease in talking aloud and out-of-seat behavior was observed for each of the
      four subjects. When the feedback apparatus was removed, the desired behavior was
      maintained through candy reinforcement alone in all four subjects.

PMID- 16795272
TI  - Inappropriate speech in a severely retarded child: a case study in language
      conditioning and generalization.
AB  - The modification of inappropriate speech, a class of behaviors rather than a
      limited number of specific examples, is little known in the severely retarded. In
      this study, operant techniques were used to modify the strikingly bizarre and
      inappropriate speech of a severely retarded boy. The boy's appropriate verbal
      responses to questions about magazine pictures were reinforced with candy. When
      he responded inappropriately, the magazine was withdrawn, and social interaction
      was discontinued for a 10-sec timeout period. Negative responses were ignored,
      the next picture displayed, and the next question asked immediately. In 10
      sessions, appropriate responses increased from 26% to 86% of all responses. A
      reversal of reinforcement was then introduced, in which inappropriate responses
      were reinforced, appropriate responses resulted in timeout, and negative
      responses were treated as before. This reduced the percentage of appropriate
      responses to 24%. Subsequent sessions of reinforcement for appropriate responses
      increased appropriate responses to 96% of all responses. At significant stages in
      the experiment, a measure of possible generalization was attempted. Although some
      generalization was recorded, it was minimal: some explanations are discussed.

PMID- 16795273
TI  - Modification of preschool isolate behavior: a case study.
AB  - A 5-yr-old preschool boy with a low rate of interaction with his nursery school
      classmates was induced to pass out candy as a tactic to increase his rate of
      interaction with them. Interaction with classmates increased markedly during the
      periods he passed out choices of candy. These changes may have been due to
      increases in both his rate of initiating activities with his classmates and to
      increases in his classmates' rate of initiating activities with him. A total time
      of less than 1 hr was required of the teacher during the experiment.

PMID- 16795274
TI  - A variable influencing the performance of generalized imitative behaviors.
AB  - This research attempted to demonstrate some of the conditions that would
      influence the performance of generalized imitative behaviors in young children.
      Two experiments were conducted. The results of Exp. I indicated that generalized
      imitative behaviors can be very durable; only one of three subjects was
      influenced by a variety of reinforcement-like procedures. Control over the
      behavior of all three subjects was obtained when a setting event involving the
      presence or absence of the experimenter was systematically varied. A second test
      of this variable was carried out in Exp. II. Results showed moderate to strong
      control over non-reinforced imitations in four preschool children.

PMID- 16795275
TI  - Eye movements as a function of response contingencies measured by blackout
      technique.
AB  - A program may have a low error rate but, at the same time, require little of the
      student and teach him little. A measure to supplement error rate in evaluating a
      program has recently been developed. This measure, called the blackout ratio, is
      the percentage of material that may be deleted without increasing the error rate.
      In high blackout-ratio programs, obtaining a correct answer is contingent upon
      only a small portion of the item. The present study determined if such low
      response-contingent material is read less thoroughly than programmed material
      that is heavily response-contingent. Eye movements were compared for two versions
      of the same program that differed only in the choice of the omitted words. The
      alteration of the required responses resulted in a version with a higher blackout
      ratio than the original version, which had a low blackout ratio. Eighteen
      undergraduates received half their material from the high and half their material
      from the low blackout-ratio version. The order was counterbalanced. Location and
      duration of all eye fixations in each item were recorded by a Mackworth Eye
      Marker Camera. On high blackout-ratio material, subjects used fewer fixations,
      shorter fixation time, and shorter scanning time. High blackout-ratio material
      failed to evoke the students' attention.

PMID- 16795276
TI  - Modification of the frequency of descriptive adjectives in the speech of Head
      Start children through modeling without reinforcement.
AB  - Children enrolled in a Head Start program were instructed to describe the
      contents of each of four boxes of toys. After the subject's initial description
      (baseline), the experimenter (model) described the contents of three boxes of
      different toys in alternation with the subject's descriptions. For one group, the
      experimenter used descriptive adjectives in his descriptions. In a second group,
      the experimenter used no adjectives of any kind. A marked increase in the
      frequency of descriptive adjectives was observed during the first description
      after modeling in the first group. This increase was maintained in successive
      descriptions at approximately the frequency used by the experimenter. Frequency
      of descriptive adjectives remained at zero or decreased in the second group.

PMID- 16795277
TI  - Operant measurement of subjective visual acuity in non-verbal children.
AB  - The present experiment sought to develop a reliable procedure for measuring
      visual acuity in non-verbal retarded children. Five non-verbal retarded children
      and two literate adults were examined. The two adults were included in the
      experiment so that verbal communication with them could validate certain
      assumptions regarding the experimental procedures. By utilizing a lever press as
      the criterion response signifying a visual discrimination and employing the
      Snellen "E" discriminanda, a reliable subjective measure was obtained, not unlike
      those measures taken from verbal adults. Contrary to several antecedent
      procedures, a relatively precise measurement of subjective acuity was shown to be
      obtainable from non-verbal retarded children. Additionally, the procedure was
      successful in evaluating the effectiveness of prosthetic lenses previously
      prescribed for two of the children.

PMID- 16795278
TI  - Voluntary control of eroticism.
AB  - A recent study reported that motivated human male subjects were able voluntarily
      to inhibit penile erection in the presence of effective erotic stimulation (Laws
      and Rubin, 1969). However, because this study required attendance only to the
      display area of erotic stimuli, there was a possibility that inhibition resulted
      from their subjects not attending to the content of the stimuli. The present
      study utilized a procedure that guaranteed subjects' attendance to the content of
      the erotic stimulation, i.e., a description of the behavioral content of the
      erotic stimulus film. Nevertheless, every subject was able to inhibit penile
      erection almost as effectively as when no film description was required.
      Furthermore, the verbal description prevented the production of competing asexual
      stimuli; a technique that all subjects, in both the Laws and Rubin study (1969)
      and the present study, reported using to inhibit penile erection when no
      description was required. This suggests that although concentration on asexual
      stimuli may be the preferred method of reducing sexual arousal to erotic
      stimulation, penile erection can be inhibited by other methods.

PMID- 16795279
TI  - Achievement Place: modification of the behaviors of pre-delinquent boys within a
      token economy.
AB  - The "pre-delinquent" behaviors of six boys at Achievement Place, a community
      based family style behavior modification center for delinquents, were modified
      using token (points) reinforcement procedures. In Exp. I, point losses contingent
      on each minute late were effective in producing promptness at the evening meal.
      During the reversal phase, threats (which were not backed up with point losses)
      to reinstate the point consequences initially improved promptness but the last
      two of five threats were ineffective. In Exp. II, point consequences effectively
      maintained the boys' room-cleaning behavior and, during a fading condition where
      the percentage of days when the contingency occurred was decreased, the point
      consequences remained effective for over six months, even when they were
      delivered on only 8% of the days. Experiment III showed that the boys saved
      considerable amounts of money when point consequences were available for deposits
      but saved little money when no points were available. Also, when points were
      given only for deposits that occurred on specific days the boys deposited their
      money almost exclusively on those days. In Exp. IV, point consequences contingent
      on the number of correct answers on a news quiz produced the greatest increase in
      the percentage of boys who watched the news and, to a lesser extent, increased
      the percentage of correct answers for the boys who watched the news. The results
      indicate that "pre-delinquent" behaviors are amenable to modification procedures
      and that a token reinforcement system provides a practical means of modifying
      these behaviors.

PMID- 16795280
TI  - A useful portable timer.

PMID- 16795281
TI  - The separate worlds of operant and non-operant psychology.

PMID- 16795282
TI  - The development of generalized imitation within topographically determined
      boundaries.
AB  - A multiple baseline technique was employed to examine the experimental
      development of an imitative repertoire within preselected topographical
      boundaries. Four severely retarded children, initially nonimitative, were
      individually trained to imitate a number of motor and vocal responses by shaping
      and fading procedures. Other untrained responses (probes) were demonstrated to
      the subjects systematically throughout the ongoing training. Training responses
      were divided into three topographical types: small motor, large motor, and short
      vocal responses. Probe responses were divided into four topographical types:
      small motor, large motor, short vocal, and long vocal responses. Following a
      multiple baseline format, sequential training of the first three types was begun
      at different temporal periods of the study; unreinforced imitative generalization
      was continually measured by the probes. Generalized imitation was observed in
      each subject (untrained responses were imitated even though unreinforced); but
      this generalization was restricted to the topographical type of imitation
      currently receiving training or having previously received training.

PMID- 16795283
TI  - Instructions and group versus individual reinforcement in modifying disruptive
      group behavior.
AB  - Head Start children were matched into two groups on the basis of rates of
      disruptive behavior during rest periods. Attempts were made to modify their
      behavior using either individual or group token reinforcement procedures. While
      the reinforcement procedures reduced inappropriate behavior somewhat, the
      addition of instructions to the reinforcement reduced the inappropriate behavior
      to near zero for both groups. Instructions alone, however, were ineffective in
      controlling behavior. Type of reinforcement (group or individual) did not produce
      differential effects. While experimental control over the target behavior was
      demonstrated, there was little carryover from the experimental room to the
      regular classroom. Even when treatment was introduced into the regular class,
      follow-up results showed that with time the target behavior approximated
      pretreatment levels. The results suggest that (a) the combination of instructions
      and reinforcement is much more effective than either one of these alone, (b)
      behavior change is specific to the environmental contingencies, and (c) the group
      reinforcement technique, which is much more easily implemented, was at least as
      effective as individual reinforcement in the present study.

PMID- 16795284
TI  - A behavioral approach to the control of thumbsucking in the classroom.
AB  - The purpose of the present study was to determine whether classroom thumbsucking
      could be controlled by making social reinforcement contingent upon appropriate
      behaviors incompatible with thumbsucking. The classroom thumbsucking behavior of
      three 8-yr-old elementary school children was observed and recorded by two
      observers. Sixteen experimental lessons were divided into sets of baseline,
      reinforcement, reversal, and representation of reinforcement. The effect of the
      experimental treatment was determined by the changes in the total thumbsucking
      level for each subject during each lesson. Results indicated noticeable decreases
      in thumbsucking rate for all three subjects during lessons in which social
      reinforcement was made contingent upon appropriate behavior. Two of the three
      subjects showed sudden increases in thumbsucking time during lessons when social
      reinforcement for appropriate responses was withheld; the third subject showed
      continued low thumbsucking time during these lessons.

PMID- 16795285
TI  - Receptive training of adjectival inflections in mental retardates.
AB  - A generalized discrimination of /er/ and /est/ suffixes as labels for stimuli
      exemplifying comparative or superlative relationships was established in three
      institutionalized retardates through differential reinforcement. The subjects
      were first taught correct pointing in response to opposite adjectives (e.g., "big
      small") presented as labels for simple visual stimuli, and then taught each of
      the comparatives, or each of the superlatives possible for those opposites (e.g.,
      "big-bigger" and "small-smaller", or "big-biggest" and "small-smallest"). As
      training proceeded, novel combinations of the training stimuli were presented as
      unreinforced probes to display any developing generalization of the training. As
      training of comparative discrimination proceeded, correct pointing response to
      comparative probes was high, but correct response to superlative probes was low.
      When training of superlative discriminations replaced training of comparatives,
      correct response to superlative probes increased, and correct response to
      comparative probes remained high.

PMID- 16795286
TI  - The teacher as observer and experimenter in the modification of disputing and
      talking-out behaviors.
AB  - Disputing and talking-out behaviors of individual pupils and entire classroom
      groups in special education classes and regular classes from white middle-class
      areas and from all black poverty areas ranging from the first grade to junior
      high school were studied. The classroom teacher in each case acted as the
      experimenter and as an observer. Various means of recording behaviors were used
      and reliability of observation was checked by an outside observer, another
      teacher, a teacher-aide, a student, or by using a tape recorder. Observation
      sessions varied from 15 min to an entire school day. After baseline rates were
      obtained, extinction of inappropriate disputing or talking-out behaviors and
      reinforcement of appropriate behavior with teacher attention, praise and in some
      cases a desired classroom activity or a surprise at the end of the week brought a
      decrease in undesired verbalizations. A reversal of contingencies brought a
      return to high levels of inappropriate talking with a return to low levels when
      reinforcement for appropriate talking was reinstated. The experiments
      demonstrated that teachers in a variety of classroom settings could obtain
      reliable observational records and carry out experimental manipulations
      successfully using resources available in most schools.

PMID- 16795287
TI  - A device for recording automatic audio tape recording.
AB  - Adaptation of a commercially available timer for use as a means of operating an
      audio tape recorder several times during the day is described. Data on a mother's
      rates of commanding her children were collected via both physically present
      observer and recorder methods in order to compare the usefulness of the
      recordings with direct observation. There was a high positive relationship
      between observer-recorder command rates, with the observer rates being
      consistently higher, when data were collected via both methods simultaneously as
      well as at different points in time.

PMID- 16795288
TI  - A note on a simple procedure for redistributing a teacher's student contacts.
AB  - A class of twelve third-grade students in a rural school of two grades per
      teacher was observed to determine the frequency of student-teacher contacts for
      each student. Requiring each child to go to a play area when he completed his
      work resulted in changing the distribution of these contacts so that the better
      students used fewer teacher contacts. In addition, the number of completed
      assignments of all students increased and data are presented which imply that the
      poorer students of the class received more of the teacher's available time than
      previously. The application of this procedure to special pupil populations would
      probably be very useful. A number of advantages and limitations of the procedure
      are described.

PMID- 16795289
TI  - An experimental analysis of anti-litter procedures.
AB  - This study evaluates the differential effectiveness of six different anti-litter
      procedures in two neighborhood theaters. The procedures used to encourage
      individuals in attendance to pick up litter and deposit it properly included:
      providing litterbags, providing litterbags with instructions to use them,
      providing extra trash cans, showing a special anti-litter film before the feature
      film, and providing incentives for the appropriate deposit of litter. In both
      theaters, the incentive procedures resulted in the removal of over 90% of all
      litter by the children in attendance, a figure far above that achieved by the
      other procedures investigated.

PMID- 16795290
TI  - The effects of access to a playroom on the rate and quality of printing and
      writing of first and second-grade students.
AB  - The major dependent variable was the rate at which first and second-grade
      students printed or wrote daily copying assignments. Data were also taken on the
      percentage of letters scored as errors according to a set of scoring criteria.
      Initially, these data were collected during a baseline condition in which each
      child returned to his seat as soon as his completed work had been scored, to wait
      for the rest of the class to finish their assignments. When the children were
      allowed to go to a playroom after their papers had been scored, there was a
      reliable increase in the mean printing or writing rates. Subsequent introductions
      of the baseline and playroom conditions replicated the relative effectiveness of
      access to the playroom to produce higher work rates. Finally, the total amount of
      time allowed for children to complete their assignments and then play was
      progressively reduced from 50 to 35 minutes. A progressive increase in work rates
      was correlated with these changes. Throughout the experiment, there was
      considerable variability in the mean number of letters scored as errors but there
      was a clear trend towards fewer errors.

PMID- 16795291
TI  - A rapid method of toilet training the institutionalized retarded.
AB  - Incontinence is a major unsolved problem in the institutional care of the
      profoundly retarded. A reinforcement and social analysis of incontinence was used
      to develop a procedure that would rapidly toilet train retardates and motivate
      them to remain continent during the day in their ward setting. Nine profoundly
      retarded adults were given intensive training (median of four days per patient),
      the distinctive features of which were artificially increasing the frequency of
      urinations, positive reinforcement of correct toileting but a delay for
      "accidents", use of new automatic apparatus for signalling elimination, shaping
      of independent toileting, cleanliness training, and staff reinforcement
      procedures. Incontinence was reduced immediately by about 90% and eventually
      decreased to near-zero. These results indicate the present procedure is an
      effective, rapid, enduring, and administratively feasible solution to the problem
      of incontinence of the institutionalized retarded.

PMID- 16795292
TI  - The effect of intermittent feedback and intermittent contingent access to play on
      printing of kindergarten children.
AB  - Intermittent grading of papers and the combination of intermittent grading with
      contingent access to play were evaluated as methods for increasing the accuracy
      of kindergarten children's printing responses. For a group of target letters,
      intermittent grading alone failed to produce an increase in accuracy, but when
      grading was paired with access to play, accuracy increased for every child. These
      results were then replicated with another letter.

PMID- 16795293
TI  - Toilet training of normal and retarded children.
AB  - Early elements in an operant chain of toilet behaviors were trained in three
      normal infants and five retarded children. Following that, eliminative behaviors
      were conditioned by operant procedures. Each child was equipped with an auditory
      signalling device that gave cues to the learner. Baseline behavior was recorded
      for a period of five days. The procedure for training consisted of two steps.
      First, a response was obtained through physical, verbal, and auditory prompts.
      Second, prompts were faded until the child responded in the presence of the
      auditory signal. When the device was removed the child performed without the
      auditory prompt. Parents were instructed in a similar procedure to enhance
      generalization in the home. Seven of the eight subjects reached a criterion and
      maintained that behavior during three criterion sessions.

PMID- 16795294
TI  - Establishing use of crutches by a mentally retarded spina bifida child.
AB  - A 5-yr-old mentally retarded spina bifida child was taught to walk with the aid
      of crutches. This behavior was developed through fading of physical prompting
      within a 10-step successive approximation sequence. Preliminary training to
      establish gait consisted of developing use of parallel bars through fading of
      physically modelled responses within a six-step successive approximation
      sequence. Use of parallel bars ceased during an extinction period and completely
      recovered upon being primed with one "free" reinforcement. Systematic use of
      natural reinforcers was employed as an aid in maintaining use of crutches.

PMID- 16795295
TI  - The effect of self-recording on the classroom behavior of two eighth-grade
      students.
AB  - The effects of self-recording on classroom behavior of two junior high school
      students was investigated. In the first experiment, study behavior of an eighth
      grade girl in history class was recorded. Following baseline observations her
      counselor provided slips for the girl to record whether or not she studied in
      class. This resulted in an increase in study. When slips were withdrawn, study
      decreased and then increased once self-recording was reinstated. After teacher
      praise for study was increased, self-recording was discontinued without
      significant losses in study behavior. In the final phase, increased praise was
      also withdrawn and study remained at a high level. In the second experiment, the
      number of talk outs emitted by an eighth-grade boy were recorded during math
      period. Following baseline, slips for recording talk outs were issued for the
      first half of the period, for the second half, and then for the entire period.
      Talk outs decreased when self-recording was in effect and increased again when
      self-recording was discontinued. When self-recording was reinstituted in the
      final phase there was a slight, though not significant decrease in talking out
      when compared to the baseline condition.

PMID- 16795296
TI  - A comparison of procedures for eliminating self-injurious behavior of retarded
      adolescents.
AB  - An attempt was made to eliminate the self-injurious behaviors of four
      institutionalized, profoundly retarded adolescents. Some of the behaviors studied
      were: face-slapping, face-banging, hair-pulling, face-scratching, and finger
      biting. Three remediative approaches to self-injurious behavior were compared.
      Elimination of all social consequences of the self-injurious behavior was not
      effective with the two subjects with whom it was attempted. The same two subjects
      were exposed to a procedure involving reinforcement of non-self-injurious
      behavior which was ineffective under no food deprivation and was effective with
      one of the two subjects under mild food deprivation. Electric-shock punishment
      eliminated the self-injurious behaviors of all four subjects with whom it was
      attempted. The results suggested that punishment was more effective than
      differential reinforcement of non-self-injurious behavior which, in turn, was
      more effective than extinction through elimination of social consequences.
      However, the effects of the punishment were usually specific to the setting in
      which it was administered. In order to eliminate the self-injurious behaviors of
      severely retarded children, it is apparently necessary to carry out the treatment
      in many of the settings in which it occurs.

PMID- 16795297
TI  - Reduction of dangerously aggressive behavior in a severely retarded resident
      through a combination of positive reinforcement procedures.
AB  - A severely retarded resident was released from a timeout chair only occasionally
      for brief periods of time. Under the timeout contingency alone, the subject made
      a choke response within minutes of being released. Attention, such as hugs,
      smiles, and candy was then increased, first by providing it non-contingently and
      continuously as long as there were no aggressive responses and then, by making it
      contingent upon incompatible responses. Under conditions of timeout plus
      increased attention, choking decreased aburptly. Grabbing responses, which
      increased when choking was reduced, were also reduced under conditions of timeout
      plus attention. Unrestrained time was gradually increased and all extra
      attention, i.e., more scheduled attention than provided other residents, was
      gradually withdrawn. When the resident was unrestrained all day and all extra
      attention was withdrawn, grabs and, to a lesser extent, chokes increased. Both
      were again reduced to a manageable level by scheduling several brief periods of
      attention each day. Hence, the program resulted in quick reductions that endured
      when the program was largely withdrawn. The changes in aggressive responding as a
      function of the presence and absence of extra attention suggest the importance of
      extra "positive reinforcement" in programs based upon positive reinforcement
      procedures and dealing with retarded residents for whom positive reinforcers may
      be scarce.

PMID- 16795298
TI  - Shock as punishment in a picture-naming task with retarded children.
AB  - Two retarded children were taught to name pictures according to a standardized
      procedure. In Exp. I, correct responses were positively reinforced on a five to
      one ratio under one stimulus condition, incorrect responses were followed with a
      sharp "no", and the subject was ignored for inattentive behavior. Under another
      stimulus condition, correct responses were reinforced as in the first condition,
      but incorrect responses and 5-sec periods of inattentive behavior were followed
      by "no" and an electric shock. Less inattentive behavior was exhibited and more
      words were learned to a pre-set criterion in the shock condition than in the no
      shock condition. In Exp. II, the ratio of inappropriate responses to shock was
      varied. The amount of inattentive behavior tended to increase in the shock
      condition, relative to that in the no-shock condition, as this ratio was
      increased. Two other measures of performance used in the present experiments were
      the ratio of errors to correct responses and the number of correct responses.
      Shock tended to produce better performance on these measures also.

PMID- 16795299
TI  - Delayed timeout as a procedure for reducing disruptive classroom behavior: a case
      study.
AB  - The disruptive behavior of a 9-yr-old boy was eliminated by the illumination of a
      light on the subject's desk, which represented the loss of free time later in the
      day. Instructions alone failed to reduce the frequency of disruptive behavior.
      When the light was removed and disruptive behavior no longer resulted in a loss
      of free time, disruptive behavior returned to its previous level.

PMID- 16795300
TI  - The modification of a child's enuresis: some response-response relationships.
AB  - The present study attempted to evaluate experimentally the relationship between
      two response classes, enuresis and oppositional behavior. One child who had a
      long history of bed-wetting was observed in his home setting. Parents' reports
      and initial observations confirmed that the child was oppositional much of the
      time. When a timeout operation and differential attention were presented,
      removed, and presented again, the frequency of oppositional behavior decreased,
      increased, and decreased accordingly. Fluctuations in enuretic activity also
      correlated with the presence and absence of the timeout and differential
      attention operations. The suppression of oppositional behavior and enuretic
      activity persisted over an 18-month treatment period. It was suggested that the
      parental operations performed on oppositional behavior may have led to an
      increase in the parents' social reward value. Cessation of enuretic activity was
      explained in terms of a shift in parental reinforcer effectiveness.

PMID- 16795301
TI  - Behavioral engineering: two apparatuses for toilet training retarded children.
AB  - Daytime incontinence is a major problem for retarded children. A training
      procedure for eliminating this problem should be facilitated by an apparatus that
      provided the trainer with an immediate signal when the child voided so that the
      trainer could react immediately. Two apparatuses were developed for this purpose:
      a toilet-chair apparatus to signal proper toileting and a portable pants-alarm
      apparatus to signal wetting of the pants. A reprimand was given when pants
      wetting occurred whereas positive reinforcement was given for proper toileting.
      Results with four profoundly retarded children indicated the reliability of the
      apparatuses in practice and the effectiveness of a toilet training program that
      used the two apparatuses.

PMID- 16795302
TI  - A comparison of students studying-behavior produced by daily, weekly, and three
      week testing schedules.
AB  - Time spent in contact with academic course materials as a function of two testing
      schedules was measured using college undergraduates in an introductory
      educational psychology course. A within-subject (ABAB) design was employed with
      all subjects to allow for both individual and group analyses. A study room
      equipped with an adjacent observation room enabled visual and auditory monitoring
      of student study behavior. Academic materials were exclusively available to
      students in the study room and records of durations and distribution of student
      study time were made by an observer behind a one-way mirror. Daily testing
      produced consistent duration of study behavior with regular attendance at the
      study room; weekly and three-week testing produced sporadic bursts of study
      behavior and frequent instances of non-attendance. The amount of study behavior
      occurring in weekly and three-week testing conditions increased as the test time
      drew near (scalloping). Results suggest that daily testing supports more
      consistent study patterns than do the two larger intertest intervals
      investigated.

PMID- 16795303
TI  - Modification of articulation errors of pre-delinquents by their peers.
AB  - Pre-delinquent peers in Achievement Place (a community based family style
      rehabilitation program based on a token economy) were given points (token
      reinforcement) to modify the articulation errors of two boys. In Experiment I,
      using a multiple baseline experimental design, error words involving the /l/,
      /r/, /th/, and /ting/ sounds were successfully treated by both a group of peers
      and by individual peers. Also, generalization occurred to words that were not
      trained. The speech correction procedure used by the peers involved a number of
      variables including modelling, peer approval, contingent points, and feedback.
      The individual role of each of these variables was not experimentally analyzed,
      but it was demonstrated that peers could function as speech therapists without
      instructions, feedback, or the presence of an adult. It was also found that
      payment of points to peers for detecting correct articulations produced closer
      agreement with the experimenter than when they were paid points for finding
      incorrect articulations. The results were replicated in a second experiment with
      another subject who had similar articulation errors. In addition, the second
      experiment showed that peer speech correction procedures resulted in some
      generalization to the correct use of target words in sentences and significant
      improvements on standard tests of articulation.

PMID- 16795304
TI  - Effects of reinforcement and guidance procedures on instruction-following
      behavior of severely retarded children.
AB  - Positive reinforcement, physical guidance, and fading procedures were used to
      teach two severely retarded children motor responses to a variety of verbal
      instructions. Subjects' responses to one set of instructions provided the focus
      for the training procedures. Their responses to a second set of instructions were
      used to assess the generalized effects of training. The frequency of responses to
      both sets of instructions was evaluated during Baseline 1, Training 1, Baseline
      2, and Training 2 periods. During the training periods, this evaluation was made
      after the daily training sessions when no training procedures were in effect.
      Results indicated that the subjects showed pronounced increases in instruction
      following behaviors (both trained and untrained) during training periods with
      decreases in such behavior occurring during the Baseline 2 period. The general
      findings demonstrate the applicability of the training procedures for producing
      and maintaining instruction-following behaviors in severely retarded children and
      for facilitating appropriate responding to instructions not directly involved in
      training.

PMID- 16795305
TI  - The effects of receptive language training on articulation.
AB  - The present study attempted to assess one condition of language exposure that
      might be operative in a normal environment, and experimentally determine its
      relevance to the acquisition of productive speech. The results demonstrated that
      the development of receptive language skills can be functionally related to
      productive speech. Specifically, the data indicated that exposure to words that
      have stimulus control over a subject's nonverbal pointing behavior can facilitate
      later articulation of those same words. Thus, this study draws attention to the
      fact that at least some classes of operants, in this case verbal, can be affected
      not only by their consequences, but by not obviously related antecedent events as
      well.

PMID- 16795306
TI  - The choices and preferences of nursery school children.
AB  - After a period of equal reinforcement for choices of any job revealed which of 10
      jobs each of 24 preschool children preferred and did not prefer, token payment
      became dependent on particular choices. Some children received tokens only for
      choosing previously non-preferred jobs, others for choosing previously preferred
      jobs. When tokens depended on choosing the nonpreferred jobs, those came to be
      preferred. When tokens depended on choosing the preferred jobs, the preferences
      were strengthened. The effects were replicated both within and between subjects,
      except in the case of one boy who consistently avoided token pay.

PMID- 16795307
TI  - Reinforcement and generalization of productive plural allomorphs in two retarded
      children.
AB  - Morphological dictates of English usage call for the unvoiced allomorph /-s/ to
      form the plural of singular nouns with unvoiced endings (e.g., cups). Conversely,
      the voiced allomorph /-z/ is required to form the plural of nouns with voiced
      endings (e.g., tree). The study sought to determine the extent to which
      differential reinforcement could control the acquisition of plural allomorphs in
      two retarded subjects. In Condition 1, one subject was trained with reinforcement
      procedures on a list of words calling for the /-s/ allomorph. She was then given
      unreinforced probe items to determine the extent of generalization to words
      calling for the /-z/ allomorph. In Condition 2, the procedures were reversed and
      this subject was trained on a /-z/ list and probed for generalization of /-z/ to
      words calling for /-s/. A second subject was exposed to the same conditions in
      the opposite order. The results for the two subjects lent unequivocal support for
      the hypothesis of generalized training effects. It was concluded that appropriate
      usage of the linguistic response class "plurals" is susceptible to generalized
      training effects of differential reinforcement.

PMID- 16795308
TI  - Systematic reinforcement: academic performance of underachieving students.
AB  - The effect of contingent tangible and social reinforcement on academic
      performance was investigated in an experimental classroom of 25 selected
      underachieving students. Measures were taken of both teacher and child behavior
      during a baseline and two experimental treatment periods. During Treatment I, a
      point system with tangible backup reinforcers was combined with contingent social
      reinforcers dispensed by the teaching staff to assess the effects on three
      measures of academic performance (i.e., per cent of time at work, work output per
      minute, and accuracy). During Treatment II, the contingencies for the tangible
      reinforcers were terminated while social reinforcement was continued to see if
      the positive effects of Treatment I on academic performance would persist. The
      results show that with combined tangible and social reinforcers, students' work
      time, rate of output per hour, and accuracy in all activities substantially
      increased. After termination of the tangible reinforcers, the students maintained
      their high rates of output per hour and accuracy for the remaining period of the
      study while the total amount of time at work returned to the baseline level.

PMID- 16795309
TI  - Engineering the behavioral engineer.
AB  - Twenty-eight nursing staff members treated, by operant methods, a simulated
      headbanging patient. They were randomly assigned to four experimental conditions,
      involving improvement versus non-improvement of the "patient" and promise of
      reward versus no promise of reward. The promise of reward significantly improved
      accuracy of treatment. Improvement of the patient, however, did not improve
      accuracy.

PMID- 16795310
TI  - A method for recording verbal behavior in free-play settings.
AB  - The present study attempted to test the reliability of a new method of recording
      verbal behavior in a free-play preschool setting. Six children, three normal and
      three speech impaired, served as subjects. Videotaped records of verbal behavior
      were scored by two experimentally naive observers. The results suggest that the
      system provides a means of obtaining reliable records of both normal and impaired
      speech, even when the subjects exhibit nonverbal behaviors (such as
      hyperactivity) that interfere with direct observation techniques.

PMID- 16795311
TI  - A device for presenting blurred visual stimuli.

PMID- 16795312
TI  - A system for monitoring and conditioning modal fundamental frequency of speech.

PMID- 16795313
TI  - The development of anti-litter behavior in a forest campground.
AB  - This study evaluates the effectiveness of an incentive procedure designed to
      induce litter collection in a large forest campground. Children in the campground
      were offered their choice of a variety of reinforcers for picking up and properly
      disposing of litter. The procedure resulted in a sharp decline in four types of
      litter planted in the campground.

PMID- 16795314
TI  - A portable, programmed, audible timer.

PMID- 16795315
TI  - Achievement Place: the reliability of self-reporting and peer-reporting and their
      effects on behavior.
AB  - The reliability of the boys reporting their own behavior of their peers was
      measured in two experiments at Achievement Place, a community based, family
      style, behavior modification program for delinquents based on a token (point)
      economy. The results of these experiments indicated that; (a) the boys were not
      "naturally" reliable observers, (b) the reliability of peer-reporting could be
      improved by providing training on the behavioral definitions and by making points
      contingent on agreement between each boy's peer-report and an independent adult
      observers' report, (c) the reliability of self-reporting could be improved by
      making points contingent on agreement between the self-report and the trained
      peer's report, and (d) giving self-reports and peer-reports did not produce a
      systematic effect on the boys' room-cleaning behavior as measured by an
      independent observer.

PMID- 16795316
TI  - Administering quiz and instructional material by overhead projector.

PMID- 16795317
TI  - Examination performance in lecture-discussion and personalized instruction
      courses.
AB  - Students enrolled in a Psychology of Learning course were assigned to either a
      lecture section, one of two similar personalized instruction sections, or a
      fourth section that rotated across all three teaching procedures. All students
      took identical midterms and a final examination. After correcting test
      performance for differences in the cumulative grade point average of students in
      the four sections, examination performance of students in the personalized
      sections was found to be superior to that of students in the lecture section. An
      analysis of class section examination performance by item type revealed that
      students in the lecture section scored lower on all item types, but the greatest
      differences occurred on items that required written responses (essay and fill-in
      items) rather than recognition responses (multiple choice items). A gross
      analysis of student performance in the class rotated across the instructional
      procedures suggests that personalized instruction had its greatest impact on
      students with "average" to "poor" academic records.

PMID- 16795318
TI  - Good-behavior game: a replication and systematic analysis.
AB  - A good-behavior game was implemented in a fifth-grade reading class consisting of
      two groups of 14 students each. After the presentation of the game, reversal and
      component analysis phases were instituted. Game components included rules, lights
      (response feedback), and group consequences of extra recess and extra free time.
      Student observers recorded the dependent variables which included talking-out,
      disruptive, and out-of-seat behaviors. The results show that the game reduced the
      dependent measures from their baseline rate by almost 99% for one group and 97%
      for the other. The component analysis revealed that after association in the
      game, the stimulus components of rules and lights were effective in reducing the
      dependent behaviors.

PMID- 16795319
TI  - Modification of behavior problems in the home with a parent as observer and
      experimenter.
AB  - Four parents enrolled in a Responsive Teaching class carried out experiments
      using procedures they had devised for alleviating their children's problem
      behaviors. The techniques used involved different types of reinforcement,
      extinction, and punishment. One parent increased the frequency of the wearing of
      an orthodontic device during five daily time checks by making an immediate
      monetary payoff contingent on wearing the device. A second parent increased the
      number of points earned for doing daily household tasks by providing back-ups for
      which the points could be exchanged. The parents of a 4-yr-old boy decreased the
      frequency of whines, cries, and complaints by removing social attention when such
      behavior occurred. A mother decreased the duration of time it took for her 5-yr
      old daughter to get dressed by making permission to watch television contingent
      on dressing within 30 min of the time she got up in the morning. Brief reversals
      of contingencies were used to show causal relationships between the procedures
      used and the changes in behavior. Checks on the reliability of measurement were
      made by persons present in the home.

PMID- 16795320
TI  - A procedure for the withdrawal of an infant oral pacifier.

PMID- 16795321
TI  - Training and maintaining a retarded child's proper eating.
AB  - The present study was designed to explore whether motivational procedures are
      needed to maintain a retardate's continued use of previously trained eating
      skills. A profoundly retarded child who ate food with her hands was trained by a
      manual guidance procedure to eat properly with a spoon, but the child still did
      not use the spoon after having learned to do so. When a motivational-maintenance
      procedure was applied, the child did begin to eat properly. When maintenance was
      discontinued, the child returned to eating with her hands. Proper eating returned
      when maintenance was applied again; when discontinued, the child returned to
      eating with her hands. These results demonstrate that continued motivational
      procedures are needed after training to maintain the retardate's continued use of
      proper eating skills.

PMID- 16795322
TI  - The noneffects of contingent reinforcement for attending behavior on work
      accomplished.
AB  - Past studies have shown that disruptive behavior can be eliminated and attending
      behavior accelerated in an academic setting. The relationship between these
      behaviors and academic performance is not well understood. The effects of
      behavioral and performance contingencies on classroom behavior and on academic
      performance were investigated. The subjects, third-grade students from an inner
      city elementary school, were exposed to a series of conditions including
      baseline, behavior contingencies, performance contingencies, and a mix of
      behavior and performance contingencies using a reversal design. The students
      worked 100 randomly selected mathematics problems for 20 minutes each day during
      each period. Behavioral contingencies improved attending and decreased
      disruptions but did not improve performance. Performance contingencies increased
      per cent correct problems but attending declined and disruptions increased. The
      combined contingencies increased both performance and attending. The experiment
      was replicated with another class of children varying the sequence of conditions
      and the amount of token reinforcement that could be earned. The findings
      emphasized the importance of designing specific contingencies for specific target
      behaviors. Behavioral contingencies did not have the positive effect on
      performance often implied, nor were performance contingencies alone able to
      maintain acceptable classroom behavior.

PMID- 16795323
TI  - Multiple effects of a procedure to increase sitting in a hyperactive, retarded
      boy.
AB  - A prompting and differential reinforcement procedure was used to increase sitting
      in a hyperactive, retarded boy in a remedial preschool. This procedure not only
      increased sitting, but had the additional effects of decreasing posturing while
      leaving normal walking unaffected, and increasing the use of toys and proximity
      to children. All of these changes can be considered socially desirable effects of
      the sitting program. The results suggest that preschool programs can be designed
      that will treat several behaviors simultaneously in order to maximize a teacher's
      effectiveness.

PMID- 16795324
TI  - Modification of arithmetic response rate and attending behavior in a seventh
      grade student.
AB  - An adjusting fixed-ratio schedule of praise and immediate correctness feedback
      produced increases in a seventh-grade student's arithemic response rate.
      Percentage of time spent in attending behavior also increased collaterally.
      Removal of the treatment led to decreases in both arithmetic response rate and
      collateral attending behavior. Reinstatements of the procedure again produced
      increases in both types of behavior. It was suggested that the present procedure
      of directly modifying arithmetic response rate requires less time and effort than
      working indirectly through modifying attending behavior.

PMID- 16795325
TI  - Timeout from positive reinforcement following persistent, high-rate behavior in
      retardates.
AB  - Brief isolation from a group situation was found to suppress persistent, high
      rate misbehavior in two extremely withdrawn children, even though no positive
      reinforcement for other behaviors was systematically administered. Changes in a
      variety of behaviors, including looking, touching, speaking, responding, and
      other non-punished misbehaviors, were observed when isolation timeout was
      administered contingent on only one misbehavior of each child.

PMID- 16795327
TI  - Time lapse automation.

PMID- 16795326
TI  - Fixed-interval work habits of Congress.
AB  - The rate at which Congress passes bills during its legislative session exhibits a
      fixed-interval pattern: the rate of passage is extremely low three to four months
      after commencement followed by a positively accelerated growth rate that
      continues until the time of adjournment. This scalloped configuration appears
      uniformly in each of the eight Congresses sampled, from 1947 to 1968, and in both
      sessions of each Congress.

PMID- 16795328
TI  - Timeout duration and the suppression of deviant behavior in children.
AB  - The effects of three different timeout durations were investigated in a group of
      20 retarded, institutionalized subjects. Each subject received 1, 15, and 30 min
      of timeout in a design that was counterbalanced in terms of the order in which
      timeout durations were presented. Displays of deviant behavior-such as
      aggression, tantrums, and self-destruction-were followed by periods of isolation
      in a timeout room. A reversal design was employed such that return-to-baseline
      periods were instituted after each timeout period. The overall effect of timeout
      was to reduce significantly the rate of deviant behavior. On the average, 15 and
      30 min produced a 35% decrease in deviant behavior with little difference between
      the effectiveness of 15 and 30 min. The range of effects in all timeout
      conditions varied widely. The sequence in which the 1-min duration was presented
      effected the direction of its effect. When it preceded the use of longer
      durations, 1 min was most effective. As it came later in the sequence, its
      suppressive characteristics became less reliable.

PMID- 16795329
TI  - A multiple change score comparison of traditional and behavioral college teaching
      procedures.
AB  - Seventy-six students in a college-level course in human development were divided
      into an experimental and a control group of approximately equal size. Both groups
      were given a pretest composed of fill-in and multiple-choice items. The control
      group was exposed to conventional educational practices while the experimental
      group was treated in a manner similar to that described by Johnston and
      Pennypacker (1971), performing only on fill-in items. Post-test results showed
      significantly greater changes in the experimental group, regardless of the type
      of test item, although the difference was greater in the case of the fill-in
      items. The results are discussed in terms of their implications for both future
      research and tactics in the development of improved teaching technologies.

PMID- 16795330
TI  - The treatment of "anxiety-depression" via positive reinforcement and response
      cost.
AB  - A target behavior program, structured within a token economy project, was
      implemented to modify the behavior of an institutionalized patient who exhibited
      excessive rates of crying and no smiling responses. To affect both responses
      concurrently, token costs were made contingent upon crying and token payments
      and/or social reinforcements were provided for smiling. The results indicated
      both the feasibility of eliminating "anxiety-depression" within an institutional
      environment and the efficacy of the treatment procedures 14 months after
      discharge.

PMID- 16795332
TI  - Dispensing liquid reinforcers.

PMID- 16795331
TI  - Training profoundly retarded children to stop crawling.
AB  - Many profoundly retarded children continue to crawl even though they can walk.
      Crawling and walking were viewed as two alternative response modes, both
      reinforced by movement. Children choose the one mode that is easier and faster
      for them. A training program was designed to increase the ease and speed of
      walking relative to that of crawling, and consisted of restraint-for-crawling and
      priming-of-walking. With the program, four retarded children reduced crawling and
      began to walk instead. When training was discontinued, two children with moderate
      walking impairment continued to walk rather than crawl. Two children with severe
      impairment of walking, however, required the occasional use of the restraint
      procedure to maintain walking as the dominant mode of locomotion. The program was
      easily administered, required little time, and was effective for all four
      children.

PMID- 16795333
TI  - Training parents as behavior modifiers: self-recording of contingent attention.
AB  - Two mothers of deviant young children were instructed to count their episodes of
      attention to appropriate child behavior in their homes, using wrist counters.
      Attention and appropriate child behavior were defined before counting began.
      Independent observations of parent-child interactions showed that, for each
      mother-child pair, the percentage of maternal attention given following
      appropriate child behavior increased, as did the child's appropriate behavior.
      Removal of the counters did not produce a reversal of the behaviors; instead the
      increased level stabilized. One mother was then instructed to count her attention
      to inappropriate child behavior and to decrease it. This instruction had little
      effect on her attention, and her child's behavior did not change. When both
      parents were again instructed to count their episodes of attention to appropriate
      behavior, further improvements in both mothers, and in their children resulted.
      These results were obtained despite inaccurate parent self-recording. Follow-up
      observations made over the next five months showed these behavioral gains to be
      durable. A third parent and his child were unaffected by this training procedure.
      Thus, there are instances in which self-recording may function as an effective
      and economical parent-training technique for effecting improvements in child
      behavior.

PMID- 16795334
TI  - A note on some reinforcing properties of university lectures.
AB  - Contingency management systems in university courses have sometimes assigned the
      role of reinforcing stimulus to lectures and demonstrations. Attending a lecture
      was made contingent upon having previously finished certain course assignments.
      The present paper investigated some variables that control student attendance at
      lectures. Attendance remained high throughout each course at those class meetings
      where quizzes contributing to course grades were given or where impending quizzes
      were discussed. Attendance at lectures over the reading assignments or over
      material unrelated to course quizzes rapidly declined. When students were given
      course credit for attending these lectures, or when the lectures included
      information for future quizzes, attendance increased. When attending these
      lectures was made contingent upon having completed certain assignments the prior
      week, no increase in assignment completion was noted and the attendance at the
      lectures decreased even further. All lectures were given during one class meeting
      each week. Attendance at the other class meetings during the week remained
      stable.

PMID- 16795335
TI  - Effects of teacher attention on digit-reversal behavior in an elementary school
      child.
AB  - Teacher attention was systematically manipulated to modify digit-reversal
      behavior in an elementary school child. Almost invariably, the child reversed the
      order of digits (e.g., writing 21 as the sum of 5 + 7) when adding numbers
      yielding a two-digit sum. The child, along with classmates, was given 20 addition
      problems a day for the duration of the study, and the number of reversals was
      recorded. During an initial baseline period, the teacher responded to digit
      reversals by marking them as incorrect and then giving the child "extra help"
      until all sums were correctly ordered. The child's present and previous teacher
      had both responded to reversals in this manner for approximately one year before
      the present study began. An experimental period followed during which the rate of
      reversals decreased sharply. During this period, all sums were marked as correct
      (whether reversed or not); "extra help" with reversals was discontinued; and
      correct, i.e., non-reversed, response forms were responded to with a smile, a pat
      on the back, and a brief comment. A reversal period followed, during which the
      teacher responded to reversals as she had in the first baseline period. An
      increase in the rate of reversals to baseline level occurred within three days. A
      final period, replicating the first experimental period followed, and was
      characterized by a sharp decrease in the rate of reversals.

PMID- 16795336
TI  - Side effects of extinction procedures in a remedial preschool.
AB  - Several studies have shown that behavior modification procedures aimed at a
      single behavior may have effects on other, nonmanipulated behaviors. A young
      retarded boy engaged in excessive conversation with his preschool teacher. The
      teacher then began to ignore his initiated conversation during free-play periods,
      and it decreased. In addition, (1) social behavior relative to children
      increased, and (2) use of girls' toys decreased during free play. Also, (3)
      appropriate behavior at group academics declined, while (4) disruptions rose. In
      a second study, the teacher alternated conditions of praise and ignoring for
      talking with children. Talking with children varied accordingly. In addition, use
      of girls' toys and group academics disruptions rose during the ignoring
      condition. Appropriate behaviors dropped. Lastly, a timeout procedure was used to
      eliminate the undesirable side effects of disruptions and of use of girls' toys.
      Apparently, a response class may have member behaviors that covary directly
      and/or inversely. Some covariations may be socially desirable, others
      undesirable. The appearance of undesirable "side effects" can be controlled using
      behavior modification techniques.

PMID- 16795337
TI  - The use of programmed materials in the analysis of academic contingencies.
AB  - Programmed handwriting materials were used to examine the effects of different
      reinforcement contingencies on the academic performance of six public school
      kindergarten children. The children's responses to these materials provided an
      educationally relevant dependent variable for the analysis of factors that
      affected the accuracy of their responses and the attainment of criterion
      performances. Variations in the complexity of most academic materials, which
      confound the analysis of contingencies, were eliminated by the programmed
      sequence so that the differential effects of three reinforcement conditions were
      observed. The three conditions were: baseline without tokens, tokens contingent
      on correct writing responses, and noncontingent tokens. It was consistently
      observed that the children were more accurate when their correct responses
      produced tokens, and that noncontingent tokens reduced accuracy below baseline
      levels.

PMID- 16795338
TI  - Stimulus factors in the training of prepositional usage in three autistic
      children.
AB  - Language deficient, autistic children were trained to use the prepositions "in"
      and "on". Three subjects were exposed to conditions of training that differed in
      the method of employment of stimulus objects used to train prepositional usage.
      Two subjects were trained first with "ambiguous" stimuli, that is, the same
      stimulus objects were used for training both prepositions. The two subjects were
      then switched to a training condition with "non-ambiguous" stimulus objects, that
      is, objects used for training "in" were different than those used for training
      "on". The two subjects were then switched to the ambiguous stimulus condition and
      finally returned again to training with non-ambiguous stimuli (four conditions).
      A third subject began with training on non-ambiguous stimuli, was switched to an
      ambiguous condition and was then switched back to non-ambiguous stimuli (three
      conditions). The results for two of the three subjects indicated that accurate
      usage of the two prepositions was obtained only under training conditions with
      non-ambiguous stimuli. Results for the third subject suggested that initial
      training with non-ambiguous stimuli might enhance subsequent accurate responding
      with ambiguous stimuli.

PMID- 16795339
TI  - A portable recording apparatus for rating behavior in free operant situations.

PMID- 16795340
TI  - An analysis-of-variance model for the intrasubject replication design.
AB  - One- and two-way analysis-of-variance procedures are shown logically to be
      appropriate for testing hypotheses in successive treatment reversal designs for
      one-subject and N-subject experiments, respectively. The applicability of these
      designs is demonstrated through analyses of typical data.

PMID- 16795341
TI  - A portable device for group modification of classroom attending behavior.
AB  - There is a need for a portable means of signalling appropriate classroom behavior
      that the teacher can carry with her as she moves about the room. An inexpensive
      wireless switch, adapted for classroom use, was used to turn on a clock when all
      children were attending to their work. When a movie was made contingent on
      accumulating a specific number of minutes on the clock, class-attending
      increased. Throughout these conditions, the records of class attending made by an
      independent observer with a stopwatch correlated highly with the remote
      controlled clock.

PMID- 16795342
TI  - A circuit for video-tape interviewing and its recording reliability.
AB  - A circuit to automate fully a standardized video-taped interview (SVTI) is
      developed. Data are reported demonstrating good instrument reliability.

PMID- 16795343
TI  - The behavior-therapeutic use of contingency contracting to control an adult
      behavior problem: weight control.
AB  - Items considered valuable by the subject and originally his property were
      surrendered to the researcher and incorporated into a contractual system of
      prearranged contingencies. Each subject signed a legal contract that prescribed
      the manner in which he could earn back or permanently lose his valuables.
      Specifically, a portion of each subject's valuables were returned to him
      contingent upon both specified weight losses and losing weight at an agreed-upon
      rate. Furthermore, each subject permanently lost a portion of his valuables
      contingent upon both specified weight gains and losing weight at a rate below the
      agreed-upon rate. Single-subject reversal designs were employed to determine the
      effectiveness of the treatment contingencies. This study demonstrated that items
      considered valuable by the subject and originally his property, could be used
      successfully to modify the subject's weight when these items were used
      procedurally both as reinforcing and as punishing consequences. In addition, a
      systematic analysis of the contingencies indicated that punishing or aversive
      consequences presumably were a necessary component of the treatment procedure.

PMID- 16795344
TI  - Programming generalization and maintenance of treatment effects across time and
      across settings.
AB  - Effects of three experimental and one control strategy were investigated in
      facilitating generalization and maintenance of treatment effects after two months
      in a token-economy classroom. At the conclusion of treatment, subjects were
      randomly assigned to one of three maintenance strategies or a control group and
      returned to their regular classrooms. The maintenance strategies were peer
      reprogramming, equating stimulus conditions between the experimental and regular
      classrooms, and teacher training in behavior management techniques. The
      maintenance strategies were implemented in the regular classroom for a two-month
      period and then terminated. Results indicated a powerful treatment effect
      produced by the token economy. Behavior maintenance effects following treatment
      were also obtained. The mean per cent appropriate behavior for the peer
      reprogramming and equating stimulus conditions strategies was significantly
      greater than the mean for the control subjects. The teacher training and control
      group means were not significantly different.

PMID- 16795345
TI  - The organization of day-care environments: "zone" versus "man-to-man" staff
      assignments.
AB  - In a large day-care center, measures of group participation were used to compare
      how much of a child's time is lost from planned activities during the daily
      transition from lunch, through the bathroom and dressing areas, to the nap area.
      Participation measures were taken using the "Zone" and "Man-to-Man" staffing
      procedures, two typical methods for dividing responsibility among teaching staff.
      In the "Zone" procedure, each teacher was assigned responsibility for a
      particular area, and for all children who passed through that area. In the "Man
      to-Man" procedure, each teacher was assigned responsibility for shepherding a
      group of designated children through all activity areas during each transition.
      The Lunch-to-Nap transition using the Zone staffing assignment was accomplished
      with a smaller decrease in child participation in planned activities than the
      transition utilizing the Man-to-Man procedure. Thus, other things being equal, it
      is recommended that the Zone procedure be used in group-care programs with more
      than one staff member, with each teacher being responsible for specific activity
      areas, rather than specific children.

PMID- 16795346
TI  - Modification of consonant speech-sound articulation in young children.
AB  - A series of three experiments was performed in a classroom setting with small
      groups of young children with severe articulation problems. Variations on a basic
      token reinforcement procedure were demonstrated in each experiment. A combined
      multiple baseline/reversal design showed effective experimenter control of rates
      of correct and incorrect consonant sound articulation in all cases. In addition,
      the data in each experiment showed the problems of obtaining stimulus
      generalization of the high rates of correct articulation to non-training
      settings. The third experiment demonstrated a procedure for producing such
      generalization by making each child a discriminative stimulus for correct
      articulaton by the other child, thus maintaining high levels of correct
      articulation for each child when in the presence of the other.

PMID- 16795347
TI  - The effects of token reinforcement and feedback on the delusional verbal behavior
      of chronic paranoid schizophrenics.
AB  - Prior research with token reinforcement in the psychiatric population has been
      directed at work adjustment, more than at major symptomatic behaviors. The
      purpose of the present research, on the other hand, was to investigate the
      effects of feedback and token reinforcement on the modification of delusional
      verbal behavior in chronic psychotics. Six male and four female paranoid
      schizophrenic patients participated in the study. The results indicated that the
      effects of feedback were effective about half the time in reducing percentage
      delusional talk, but in at least three cases produced adverse reactions. Token
      reinforcement, however, showed more consistency and reduced the percentage of
      delusional verbal behavior in seven of the nine subjects exposed to this
      procedure. The effects of both feedback and token reinforcement were quite
      specific to the environment in which they were applied and showed little
      generalization to other situations. It would appear that using token
      reinforcement can reduce the percentage delusional speech of chronic paranoid
      schizophrenics.

PMID- 16795348
TI  - Intrinsic reinforcers in a classroom token economy.
AB  - An inexpensive, easily managed token economy was used in a normal classroom for
      one academic year, and data were collected for the entire academic performance in
      spelling, language, handwriting, and math for that year. During a baseline
      period, assignment completion was variable. The introduction of a token economy
      with a point exchange every five days increased assignment completion and
      decreased variability of performance. An application of a token economy that had
      a point exchange averaging four days was accompanied by an assignment completion
      rate that approximated 100%. A reinforcement contingency for which quiet behavior
      rather than for assignment completion was eased quiet behavior was accompanied by
      a marked diminution of assignment completion. A reintroduction of the token
      reinforcement for assignment completion system increased assignment completion
      again.

PMID- 16795349
TI  - An analysis of timeout and response cost in a programmed environment.
AB  - A group of mildly retarded adolescents with high rates of antisocial behavior was
      exposed to two parameters of timeout and response cost within the context of a
      programmed environment. For five of the six subjects, the two higher values (30
      tokens response cost or 30 min timeout) were significantly more suppressive than
      the lower values (five tokens or 5 min). For the one remaining subject, there was
      a strong relationship in the opposite direction. Also, the timeout and response
      cost of higher value became increasingly more suppressive over time, whereas
      those of lower value did not. There were few appreciable differences between the
      timeout and response cost of similar magnitude. A discussion of these results is
      presented in support of the notion that the functional aversiveness of timeouts
      (and response costs) appears to be critically dependent upon interactions with
      the environmental conditions in which they are implemented and the reinforcement
      histories of the subjects.

PMID- 16795350
TI  - Academic responses and attitudes engendered by a programmed course in child
      development.
AB  - Both a small course section and a large course section were taught with methods
      that involved breaking material down into weekly units that had to be mastered by
      students as indicated by weekly tests. Attendance at lectures was voluntary and
      students were not tested on lecture material. In a system in which a student
      could receive only an A or an F for a course grade, less than 2% of the students
      receiving credit failed to master all material and received Fs. Students in the
      large course performed better on weekly tests and received fewer Fs than their
      counterparts in the small course, even though they rated their experience less
      favorably. Within the large course, the methods of tutorial interview, group
      discussion, and written assignment were compared in terms of their effectiveness
      in preparing students for weekly tests. Tutorials and written assignments were
      superior to group discussions in this regard. Students rated the effectiveness
      and enjoyability of these three methods in the reverse order from their actual
      effectiveness for test preparation. Some consequences of lack of congruity
      between attitude measures and performance measures were discussed.

PMID- 16795351
TI  - Reward, cost, and self-evaluation procedures for disruptive adolescents in a
      psychiatric hospital school.
AB  - Sixteen pupils in a psychiatric hospital were assigned to two tutorial reading
      classes and balanced on six pupil characteristics and teacher preferences for the
      children. The effects of reward and cost procedures in a token program were
      assessed using both within- and between-subject comparisons in the following
      phases: (1) Baseline; (2) Token I, teacher evaluated and reinforced children for
      appropriate behavior; (3) Withdrawal of Tokens; (4) Token II, same as Token I;
      (5) Token III, same as Token I and II, but switched order of class meeting time;
      and (6) Self-Evaluation, students rated their own behavior and received prizes
      based on their rating, rather than the teacher's rating. The token program was
      markedly successful in reducing disruptive behavior and in increasing reading
      skills in both the Reward and Cost Classes, but there were no significant
      differences in the effects of the reward versus the cost procedure. While cost
      may be seen as a punishment procedure, there were no adverse side effects
      observed in the Cost Class at any time when the token program was in effect. The
      order of the classes was unrelated to the level of disruptive behavior or
      academic progress. The Self-Evaluative Phase, in which the students rated their
      own behavior, was included as an alternative to the abrupt withdrawal of tokens.
      In this phase, disruptive behavior remained at the previous low level.

PMID- 16795352
TI  - The effects of fading on the acquisition and retention of oral reading.
AB  - Comparisons were made between reading programs that involved superimposition of
      correlated pictoral and printed stimuli, fading of the pictoral stimuli, and
      overt observing (touching) responses. Nursey school children aged 4 to 5.8 yr
      learned and retained oral reading behavior better when fading was used; observing
      responses had no effect.

PMID- 16795353
TI  - The effect on the test behavior of children, as reflected in the I.Q. scores,
      when reinforced after each correct response.
AB  - This experiment studied the effect on intelligence test scores of a probable
      reinforcer given for correct responses. Eleven pairs of 5- to 7-yr-old children
      were matched on the basis of a strong liking of candy, no physical problems
      associated with eating it, parent permission to receive and eat the candy, age,
      sex, and a revised Stanford-Binet Scale Form L IQ score. The control group was
      given the revised Stanford-Binet Scale Form M, as prescribed in the test manual.
      The experimental group was also given Form M according to the manual, except M&M
      candy was given for each plus or correct response. There was an appreciable,
      statistically significant difference between the resulting IQ test scores of the
      two groups.

PMID- 16795354
TI  - Teaching a complex verbal response to a hearing-impaired girl.
AB  - A 3-yr-old hearing-impaired girl, who used neither the article "the" nor the
      auxiliary verb "is" was taught to use these words in describing a picture,
      initially through imitation and then in response to the command, "Tell me about
      this". As a result, she was able to use sentences in the present progressive form
      to describe a number of pictures on which she had received no training. This
      newly acquired behavior was subsequently extinguished and then reinstated.

PMID- 16795355
TI  - Reducing and measuring inappropriate verbalizations in a token classroom.
AB  - A procedure was employed that enabled a teacher to bring inappropriate
      verbalizations under control in a classroom of approximately 25 fifth- and sixth
      grade students. Contingent point loss for inappropriate verbalizations was
      correlated with a low but steady rate of such verbalizations. Point gain
      contingent upon quiet behavior produced a marked decrease in inappropriate
      verbalizations. A return to contingent point loss was accompanied by an
      increasing rate of inappropriate verbalizations. Verbalizations decreased when
      quiet behavior was reinforced again. A noteworthy feature of the study was the
      utilization of students from within the class to act as data recorders. A
      reliability check indicated satisfactory agreement between the recorders.

PMID- 16795356
TI  - Behavioral economics: areas of cooperative research between economics and applied
      behavioral analysis.
AB  - The current research methods of behavioral economics are characterized by
      inadequate empirical foundations. Psychologists involved in the experimental
      analysis of behavior with their research strategies and their experimental
      technology, particularly that of the Token Economy, can assist in providing
      empirical foundations for behavioral economics. Cooperative research between
      economists and psychologists to this end should be immediately fruitful and
      mutually beneficial.

PMID- 16795357
TI  - Reviewer's comment.

PMID- 16795360
TI  - Reviewers' comments.

PMID- 16795359
TI  - Item preference in a token economy ward store.
AB  - Token spending by 20 schizophrenic patients was monitored over a six-month
      period. It was found that: (1) token expenditures for cigarettes and "edibles"
      far surpassed other store item categories; and (2) percentage increases in token
      expenditures were greatest for categories of items relating to appearance and
      grooming, strongly suggesting that store purchasing patterns over time may
      provide an index of program effectiveness.

PMID- 16795358
TI  - The token economy: an evaluative review.
AB  - Token economies have been applied in a wide range of settings. While there are
      several advantages to the use of this procedure, there are obstacles that may
      impede its implementation and therapeutic efficacy. These include: staff
      training, client resistance, circumvention of the contingencies, and non
      responsiveness of subjects. Studies employing token programs with psychiatric
      patients, retardates, children in classroom settings, delinquents, and autistic
      children are reviewed. Although token economies are successful while in
      operation, the issue of generalization of behavior gains or resistance to
      extinction has not been given careful consideration. Inasmuch as generalization
      is perhaps the most crucial issue, several procedures are presented that are
      designed to facilitate maintenance of performance when reinforcement is
      withdrawn. Methodological suggestions for investigations on token reinforcement
      in applied settings are presented.

PMID- 16795361
TI  - A portable observation-experimental booth.

PMID- 16795362
TI  - The relationship of self-stimulation to learning in autistic children.
AB  - The acquisition of discriminative behavior was studied in three autistic children
      with high-frequency self-stimulatory behavior. It was found that: (a) the
      children did not acquire the discrimination while engaged in self-stimulation;
      (b) suppression of self-stimulation produced an increase in correct responding,
      with eventual acquisition of the discrimination; (c) successful discrimination
      learning was always associated with a reduction in self-stimulatory behavior,
      even when aversive stimuli were not used for suppression.

PMID- 16795363
TI  - Developing proper mealtime behaviors of the institutionalized retarded.
AB  - The institutionalized mentally retarded display a variety of unsanitary,
      disruptive, and improper table manners. A program was developed that included (1)
      acquisition-training of a high standard of proper table manners and (2)
      maintenance procedures to provide continued motivation to maintain proper
      mealtime behaviors and decrease improper skills. Twelve retardates received
      acquisition training, individually, by a combination of verbal instruction,
      imitation, and manual guidance. The students then ate in their group dining
      arrangement where the staff supervisor provided continuing approval for proper
      manners and verbal correction and timeout for improper manners. The results were:
      (1) the trained retardates showed significant improvement, whereas those
      untrained did not; (2) the trained retardates ate as well in the institution as
      non-retarded customers did in a public restaurant; (3) proper eating was
      maintained in the group dining setting; (4) timeout was rarely needed; (5) the
      program was easily administered by regular staff in a regular dining setting. The
      rapidity, feasibility, and effectiveness of the program suggests the program as a
      solution to improper mealtime behaviors by the institutionalized mentally
      retarded.

PMID- 16795364
TI  - The role of proctoring in personalized instruction.
AB  - The effect of amount of student-proctor interaction was investigated within the
      framework of Keller's (1968) method of personalized instruction. College students
      enrolled in introductory psychology were randomly assigned to five groups: 0%,
      25%, 50%, 75%, and 100%, reflecting the percentage of units on which each student
      was proctored. The results indicated that (a) the proctored students were
      superior to the non-proctored students as measured by final examination
      performance, (b) for the proctored groups, the amount of proctoring did not
      differentially affect final examination performance, and (c) the major effect of
      increased proctoring was an acceleration of the rate of progress through the
      course.

PMID- 16795365
TI  - The organization of day-care environments: required versus optional activities.
AB  - Measures of group participation were used in an experimental analysis of the
      effects of two preschool activity schedules. Children's participation in
      preschool activities remained as high when children were allowed no options but
      were required to follow a schedule of activities in sequence, as when they were
      free to choose between several optional activities. However, this was only true:
      (1) when a child was not forced to wait until all other children had finished,
      but could start the next required activity individually as soon as he had
      finished the preceding one, and (2) when there was an abundance of materials in
      each required activity. When there were not adequate materials in each activity,
      children's participation was disrupted unless they were free to choose among
      several optional activities. Thus, in order to maintain high levels of
      participation in preschool play activities, it is not necessary to allow children
      to choose among several alternative activities. High participation may be more
      efficiently maintained by providing a supply of materials that is adequate to
      occupy all children in each of a sequence of required activities and staffing by
      at least two teachers, so that while one teacher is supervising children still
      finishing one activity another teacher can supervise children who are ready to
      start the next.

PMID- 16795366
TI  - Analysis of the effects of sequential reinforcement contingencies on aspects of
      composition.
AB  - The procedures of manipulating consequent events were applied to the problems of
      teaching composition in a fifth-grade remedial classroom. Three objective aspects
      of composition, total number of words, number of different words, and number of
      new words, were selected for manipulation and reinforcement contingencies were
      sequentially applied to these components. The writing output of all subjects was
      greatly increased.

PMID- 16795367
TI  - Parametric effects of reinforcement frequency, amount of reinforcement, and
      required response force on sheltered workshop behavior.
AB  - Three experiments involving parametric manipulation of reinforcement
      contingencies were performed with retardates in an automated Sheltered Workshop
      token economy. Experiment I showed that with amount of reinforcement held
      constant, work rates were positively related to reinforcement rates on fixed
      interval schedules and inversely related to reinforcement rates on fixed-ratio
      schedules. Experiment II demonstrated an interaction between frequency of ratio
      reinforcement and torque required to complete a work unit: work rates were
      positively related to reinforcement rates when required response force was high
      and negatively related to reinforcement rates when required response force was
      low. Experiment III revealed that, with reinforcement frequency held constant,
      there was in inverse relationship between amount of reinforcement and work rate.

PMID- 16795368
TI  - Self-regulation in the modification of disruptive classroom behavior.
AB  - This study compared self-regulation and external regulation procedures in the
      treatment of children's disruptive classroom behavior. After baseline data were
      collected, three of the four most disruptive children in each of 10 first- and
      second-grade classrooms received reinforcement for achieving low rates of
      disruptive behavior. The fourth child served as a control subject throughout the
      experiment. Two of the three experimental subjects were then taught to self
      observe their own disruptive behavior. In the final reinforcement period, these
      subjects were given control over dispensing reinforcers to themselves, based on
      their self-collected behavioral data while subjects in the other experimental
      group continued with the externally managed reinforcement. In extinction,
      reinforcement was discontinued for all subjects, but one of the self-regulation
      subjects in each classroom continued overtly to self-observe. Results indicated
      that both reinforcement programs reduced disruptive behavior. The self-regulation
      procedures were slightly more effective in reducing disruptiveness than was the
      external regulation procedure, and this advantage persisted into extinction.
      These results suggest that self-regulation procedures provide a practical,
      inexpensive, and powerful alternative in dealing with disruptive behavior in
      children.

PMID- 16795369
TI  - Training letter discrimination in four-year-old children.
AB  - Four-year-old children were tested on letter discrimination. Subjects in two
      experimental groups went through an experimental training program on a match-to
      sample apparatus. Subjects in the experimental-critical group were given
      reinforcers for responding to features of the stimuli thought critical for
      discriminating letters while subjects in the experimental-noncritical group were
      given reinforcers for responding to non-critical features. Subjects went through
      the training program daily until they reached criterion; then they were
      posttested on letters. Subjects in a control group received no training but were
      posttested. Subjects in all groups made fewer errors on the posttest. Subjects in
      the experimental-critical group made significantly fewer posttest errors than
      subjects in the experimental-noncritical group, lending support to the hypothesis
      that reinforcement of discriminative responding to critical features of letter
      like stimuli results in greater improvement in letter discrimination than
      reinforcement of discriminative responding to noncritical features of stimuli.
      Analysis of confusion matrices provided tentative indications of the nature of
      letter confusions in 4-yr-old children.

PMID- 16795370
TI  - The effect of incongruent instructions and consequences on imitation in retarded
      children.
AB  - Three retarded boys served as subjects in a 13-phase experiment. In eight of
      these phases, the instructions administered by the experimenter before
      demonstrating a behavior and the consequences for imitative behavior were
      incongruent (the consequences were not those indicated by the instructions).
      Consequences rather than instructions controlled imitative behavior when (a)
      subjects were instructed not to imitate but received reinforcers if they
      imitated; (b) subjects were instructed to imitate but were differentially
      reinforced for other behavior; (c) subjects were instructed to imitate but were
      verbally reprimanded for imitation. Although subjects were highly imitative at
      the beginning of the study, when there was no reinforcement for imitation
      subjects gradually stopped imitating when instructed not to imitate. Instructions
      seemed to control imitative behavior when there was no reinforcement for
      imitation and subjects were instructed to imitate. These results indicated a need
      for further investigation of antecedent and consequent variables in imitation
      experiments and pointed out that certain techniques may be more efficient than
      others in eliminating well-established responses.

PMID- 16795371
TI  - Effects of reinforcement on standardized test performance.
AB  - The effects of two different motivational conditions upon standardized test
      performance were explored for two student populations. The first study involving
      12 trainable retardates showed a significant increase in score on the
      Metropolitan Readiness Test given under reinforcement conditions when these
      results were compared with scores taken under standard testing conditions. In a
      second study, these same results were obtained with a group of 30 normal fourth
      graders. An additional study was conducted to determine the effect of different
      experiences with token reinforcement procedures on test performance. It was found
      that a group of children with six weeks' exposure to reinforcement for daily
      academic performance scored higher under both conditions of test administration
      (standard and reinforcement) than a control group. However, in a single exposure
      to token reinforcement for correct performance on the Metropolitan Test, both the
      experimental group and its match control showed a parallel increase in test
      performance. These findings offer a procedure that yields a more representative
      assessment of a student's academic achievement than does testing under standard
      conditions.

PMID- 16795372
TI  - The home point system: token reinforcement procedures for application by parents
      of children with behavior problems.
AB  - Parent-child problems within the home are frequently reported to be instances in
      which children refuse to help with household chores, bicker among themselves, or
      engage in verbally inappropriate behavior toward their parents. The present study
      investigated the effects of a token reinforcement program administered by the
      parents in ameliorating these problems. Two sets of parents, with a total of five
      children between the ages of 5 and 10 yr, were taught to administer a token
      economy within their homes. The parents received instruction in specifying
      desired social and chore behaviors, communicated these behavioral goals to their
      children, recorded data on their occurrence, and managed a point system backed
      with reinforcers normally found in the home. The token reinforcement program was
      shown to have successfully modified 15 problem behaviors in Family 1 and six in
      Family 2. In addition, the parents rated all 21 behavior changes as significant
      improvements. These studies indicated that some cooperative parents need only a
      small amount of professional help to learn to manage their children's behavior
      problems with token reinforcement procedures.

PMID- 16795373
TI  - Current behavior modification in the classroom: be still, be quiet, be docile.
AB  - Classrooms have recently been criticized as total institutions where there is a
      rigid preoccupation with order and control, and where children are required to be
      still, to be silent, and to obey. Behavior modification has been described as a
      major source of change in the classroom. A review of this journal's papers on
      behavior modification in the classroom indicated that inappropriate behavior has
      been consistently defined as behavior that interferes with order, quiet, and
      stillness. It is argued therefore, that behavior modification has supported
      rather than changed the questionable status quo. Alternative areas for behavior
      modification in traditional classrooms and the role of behavior modification in
      the development of open classrooms are discussed.

PMID- 16795374
TI  - Behavior modification in the classroom: a rejoinder to Winett and Winkler.
AB  - Winett and Winkler aptly criticized the "appropriate" behaviors that behavior
      modifiers have chosen to change. However, after reviewing 14 Journal of Applied
      Behavior Analysis articles concerning behavior modification in the classroom,
      they made the sweeping over-generalization that "as currently practised, behavior
      modification has done very little to change the deplorable state of our schools."
      Finally, they suggest a free classroom in which learning is accompanied by
      "singing, laughing, and whistling." A number of studies not mentioned by Winett
      and Winkler are here presented to illustrate the innovative ways in which
      behavior modification has been utilized to change the complexion of classrooms
      from the elementary school to the college level. A strawman model child as
      purportedly seen by behavior modifiers was built by Winett and Winkler, but this
      author could not find one instance in the literature where the teacher or
      behavior modifier desired the behavior thus depicted by the straw-man model
      child. Furthermore, this author questions the desirability of the "informal" or
      "free" classroom approach for children with marked social and academic problems.
      Nonetheless, the general admonition of Winett and Winkler should definitely by
      taken seriously-namely the behavior modifier should seriously question the
      behaviors he is being asked to change. Finally, a possible integration of
      reinforcement principles and some aspects of the informal school are discussed.

PMID- 16795375
TI  - Current behavior modification in the classroom: reviewers' comments.

PMID- 16795376
TI  - Teaching behavior modification to nonprofessionals.
AB  - Two instructional methods (role playing and lecture) were compared in evaluating
      the effectiveness of teaching behavior modification to institutional attendants.
      Pre- and post-test measures were obtained for two major outcome variables: (1)
      knowledge of behavior modification principles and (2) ratings of ability to apply
      behavior modification techniques. Results indicated that role playing was more
      effective in teaching behavior modification skills while the lectures were more
      effective in teaching principles of behavior modificaiton.

PMID- 16795378
TI  - An inexpensive auditory stimulus device for use with children.

PMID- 16795377
TI  - Automated transduction of sheltered workshop behaviors.
AB  - This study describes techniques for attaching transducers directly to the tools
      in a sheltered workshop. The resulting automatic recordings of tool usage
      correlate fairly highly with independent measures of work products completed.

PMID- 16795379
TI  - A low-cost, rapid delivery point system with "automatic" recording.

PMID- 16795380
TI  - The elimination of autistic self-stimulatory behavior by overcorrection.
AB  - No method is in general usage and of demonstrated effectiveness in eliminating
      the self-stimulatory behaviors of retardates and autistics. An Overcorrection
      rationale was used to develop such a method. The Overcorrection procedures
      consisted of a period of practice in the correct mode of the behavior contingent
      upon self-stimulatory behavior. The procedures were applied in a behavioral day
      care program to three retarded children and one autistic child who exhibited
      object-mouthing, hand-mouthing, head-weaving and hand-clapping. For some
      behaviors, comparisons were made between the Overcorrection procedure and several
      alternative procedures, such as physical punishment by a slap, reinforcement for
      nonself-stimulatory behavior, a distasteful solution painted on the hand of a
      hand-mouther, and free reinforcement. The Overcorrection procedures eliminated
      the self-stimulatory behaviors of all four children in tutorial sessions and
      during the entire school day and were more effective than the alternative
      procedures in eliminating self-stimulation. The Overcorrection procedures appear
      to be rapid, enduring, and effective methods of eliminating self-stimulatory
      behavior.

PMID- 16795381
TI  - Control of an obscene "verbal tic" through timeout in an elementary school
      classroom.
AB  - A classroom teacher modified the behavior of a 10-yr-old student who had a high
      rate of obscene vocalizations accompanied by facial twitches. In the first phase,
      the subject was instructed to repeat rapidly the most frequent obscene word in
      four daily 15-min sessions. This procedure reduced the frequency of obscene
      vocalizations, but not to an acceptable level. Subsequently, the teacher was able
      effectively to control the target behavior using a timeout procedure.

PMID- 16795382
TI  - Behavioral self-control of on-task behavior in an elementary classroom.
AB  - Techniques of behavioral self-control were employed in a class where a high level
      of on-task behavior had been established with externally administered
      reinforcement procedures. The behavioral self-control techniques maintained
      behavior at its ongoing high level both immediately following the externally
      administered reinforcement treatments and during follow-up treatments after five
      and seven weeks. Variability in on-task behavior was reduced during the
      behavioral self-control phases of the study.

PMID- 16795383
TI  - Independent control of a pre-school child's aggression and peer interaction by
      contingent teacher attention.
AB  - This study demonstrated the existent role of contingent teacher attention in
      maintaining a preschool child's aggression to his peers, as well as an imposed
      use of contingent teacher attention to increase his low peer interaction.
      Aggression and peer interaction were analyzed independently as two baselines of
      multiple baseline design; each was subjected to at least one reversal. The
      multiple baseline design was used to examine three possibilities: (1) that the
      high rate of aggressive behavior was in itself impeding the emergence of peer
      interaction; (2) that contingent teacher attention could be used to maintain a
      reduced rate of aggressive behavior; and (3) that a similar use of teacher
      attention could maintain an increased rate of peer interaction. The technique of
      largely ignoring the subject's aggressive behavior and attending instead to
      whatever child he was attacking decreased his aggressive behavior to an
      acceptable rate. Two reversals of this technique displayed experimental control,
      each recovering the high baseline rate of aggression. After the aggressive
      behavior was decreased for the final time, teachers attended to the subject only
      when he was involved in social interaction with peers, and they thus increased
      his social interaction to a high rate. Later, they withdrew their attention for
      social interaction and reversed the effect and finally then recovered it.

PMID- 16795384
TI  - Reducing latency of a child's responding to instructions by means of a token
      system.
AB  - The response latency of following directions by an 8-yr-old boy from a class for
      emotionally disturbed children was modified by the contingent application of a
      token system. To demonstrate reinforcer effectiveness, a multiple baseline
      approach was used. Measures were obtained for the time elapsed between the
      presentation of verbal directions and five performances: (1) entering the
      experimental room, (2) putting toys away, (3) beginning academic work, (4)
      putting toys away again, and (5) returning to the classroom and completing
      preparations for leaving school. These five measures were placed on the token
      system at three different times. The results demonstrated that four of the five
      performances were clearly affected by the token system as their response latency
      for following directions decreased substantially.

PMID- 16795385
TI  - Some generalization and follow-up measures on autistic children in behavior
      therapy.
AB  - We have treated 20 autistic children with behavior therapy. At intake, most of
      the children were severely disturbed, having symptoms indicating an extremely
      poor prognosis. The children were treated in separate groups, and some were
      treated more than once, allowing for within- and between-subject replications of
      treatment effects. We have employed reliable measures of generalization across
      situations and behaviors as well as across time (follow-up). The findings can be
      summarized as follows: (1) Inappropriate behaviors (self-stimulation and
      echolalia) decreased during treatment, and appropriate behaviors (appropriate
      speech, appropriate play, and social non-verbal behaviors) increased. (2)
      Spontaneous social interactions and the spontaneous use of language occurred
      about eight months into treatment for some of the children. (3) IQs and social
      quotients reflected improvement during treatment. (4) There were no exceptions to
      the improvement, however, some of the children improved more than others. (5)
      Follow-up measures recorded 1 to 4 yr after treatment showed that large
      differences between groups of children depended upon the post-treatment
      environment (those groups whose parents were trained to carry out behavior
      therapy continued to improve, while children who were institutionalized
      regressed). (6) A brief reinstatement of behavior therapy could temporarily re
      establish some of the original therapeutic gains made by the children who were
      subsequently institutionalized.

PMID- 16795386
TI  - Adverse effects of differential parental attention.
AB  - In two independent parent training projects (Kansas and Mississippi), mothers of
      deviant young children were observed to follow almost all child behaviors with
      attention. The mothers were then trained to use differential attention procedures
      to increase their child's appropriate behaviors and to decrease deviant
      behaviors. Contrary to expectations, the differential attention procedure
      produced substantial increases in deviant behavior for four of the children. This
      adverse effect was maintained over many sessions and was replicated in single
      organism, reversal designs. A fifth child showed no change. A sixth child showed
      some improvement. However, this effect was not recovered in a second application
      of differential attention, and the child became worse. The results underline the
      importance of subject generality in applied behavior analysis and strongly
      suggest that service programs using operant techniques must carefully evaluate
      their effects on behavior.

PMID- 16795387
TI  - Reviewers' comments.

PMID- 16795388
TI  - Toward the certification of behavior therapists?
AB  - The issue of certification of behavior therapists is considered. The existence of
      potentially measurable performance criteria for behavior therapists suggest that
      certification is possible. It is argued that steps toward certification will tend
      to separate experimenter and clinician, and foster separation of behavior
      modification and therapy from closely related fields of enquiry. Behavior
      modifiers should work within existing professional organizations to strengthen
      current licensing and certification procedures, rather than form their own
      certifying body.

PMID- 16795389
TI  - Reviewers' comments.

PMID- 16795391
TI  - Reviewers' comment.

PMID- 16795390
TI  - Measuring the reliability of observational data: a reactive process.
AB  - Reliability of observational data was measured simultaneously by two assessors
      under two experimental conditions. During overt assessment, observers were told
      that reliability would be measured by one of the two assessors, thus permitting
      computation of reliability with an identified and an unidentified assessor.
      During covert assessment, observers were not informed of the reliability
      measured. Throughout the study, each of the assessors employed a unique version
      of a standard observational code. In the overt assessment condition, reliability
      of observers with the identified assessor was consistently higher than
      reliability with the unidentified assessor, indicating that observers modified
      their observational criteria to approximate those of the identified assessor. In
      the covert assessment condition, reliability with the two assessors was
      substantially lower than during overt assessment. Further, observers consistently
      recorded lower frequencies of disruptive behavior than the two assessors during
      covert assessment.

PMID- 16795392
TI  - The control of the content of conversation through reinforcement.

PMID- 16795393
TI  - Achievement Place: experiments in self-government with pre-delinquents.
AB  - One of the goals of many treatment programs for pre-delinquent youths is the
      development of the skills involved in the democratic decision-making process. At
      Achievement Place, one aspect of the treatment program is a semi-self-government
      system whereby the seven pre-delinquent youths can democratically establish many
      of their own rules of behavior, monitor their peers' behavior to detect
      violations of their rules, and conduct a "trial" to determine a rule violator's
      guilt or innocence, and to determine the consequences for a youth who violates a
      rule. Two experiments were carried out to determine the role of some of the
      procedures in the boys' participation in the self-government system. Experiment I
      showed that more boys participated in the discussion of consequences for a rule
      violation when they had complete responsibility for setting the consequence
      during the trials than when the teaching-parents set the consequence for each
      rule violation before the trial. An analysis of the rule violations in this
      experiment indicated that the boys in Achievement Place reported more of the rule
      violations that resulted in trials than reported by the teaching-parents or
      school personnel. The boys reported rule violations that occurred in the
      community and school as well as at Achievement Place, including most of the
      serious rule violations that came to the attention of the teaching-parents. In
      Experiment II, the results indicated that more trials were called when the
      teaching-parents were responsible for calling trials on rule violations reported
      by the peers than when the boys were responsible for calling trials. When the
      youths earned points for calling trials the average number of trials per day
      increased, but more trivial rule violations were reported. These results suggest
      that aspects of the democratic decision-making process in a small group of pre
      delinquents can be studied and variables that affect participation can be
      identified and evaluated.

PMID- 16795394
TI  - Peer reinforcement control of classroom problem behavior.
AB  - Peer and teacher interactions with five "disruptive" children were studied in an
      elementary school classroom. The intent of the study was to analyze
      experimentally peer reinforcement control of the disruptive children's problem
      behaviors. Social attention provided by all peers was found to be directed
      exclusively to the problem behaviors during baseline. Following baseline, several
      manipulations of selected peer social attention demonstrated the reinforcement
      function of this stimulus class.

PMID- 16795395
TI  - Reducing delusional speech in chronic, paranoid schizophrenics.
AB  - Four schizophrenic patients with paranoid and grandiose delusions who had been
      hospitalized for an average of 17 yr were exposed to social reinforcement
      contingencies in a multiple baseline design. During the baseline period, each
      patient was interviewed for four 10-min sessions each day. The elapsed time from
      onset of conversation to onset of delusional talk was recorded. At the end of
      each day, the patients engaged in a 30-min informal chat with a nurse-therapist
      while relaxing with coffee, snacks, and cigarettes. The intervention introduced
      two contingencies: (1) The 10-min interviews were terminated as soon as the
      patient began talking delusionally; (2) The patients earned time for their
      evening chat by talking rationally during their daytime interviews. Increases of
      from 200 to 600% in the amount of rational talk exhibited during the interviews
      occurred as the contingencies were introduced for each patient sequentially over
      time. These increases were maintained in three patients when the amount of
      reinforcement was halved, but declined when the patients were confronted directly
      with their delusional ideas. A modest amount of generalization occurred from the
      day-time interviews to the evening chats but did not extend to the behavior of
      the patients on the ward.

PMID- 16795396
TI  - Conditioning and post-hospital generalization of nondelusional responses in a
      chronic psychotic patient.
AB  - An operant conditioning approach was successful in getting a chronic psychotic
      patient to give factual answers to direct questions that had previously elicited
      only delusional responses. Multiple baseline and reversal controls established
      that the changes were due to the experimental procedure. The subject was a female
      patient classified as paranoid schizophrenic who had persisted in giving bizarre
      responses to direct questions regarding her identity, age, and personal history
      during 26 yr of hospitalization. She was discharged after factual answers to
      these questions had been obtained, but operant conditioning trials were continued
      in the community to promote generalization. Two follow-up interviews were
      conducted 36 and 52 days after discharge to evaluate generalization. No
      generalization was found in the first interview, but the second gave evidence of
      some generalization.

PMID- 16795397
TI  - The effect of vicarious reinforcement on attentive behavior in the classroom.
AB  - The effect of social reinforcement delivered to target subjects on the attentive
      behavior of adjacent peers was examined in a classroom setting. In a combined
      reversal and multiple baseline design, two pairs of mentally retarded children
      were sequentially exposed to three reinforcement phases. After baseline rates of
      attentive behavior were obtained, praise was delivered to the target subject in
      each subject pair for attentive behavior. After a reversal phase, praise was
      delivered contingently to target subjects for inattentive behavior. In a final
      phase, contingent praise for attentive behavior was reinstated for the target
      subjects. Throughout the study, nontarget subjects received no direct
      reinforcers. The results indicated a vicarious reinforcement effect. Reinforcing
      attentive behavior of target subjects increased this behavior in adjacent peers.
      However, reinforcing inattentive behavior of target subjects also increased the
      attentive behavior of adjacent peers. The effects obtained through vicarious
      reinforcement were considered to reflect the discriminative stimulus properties
      of reinforcement, which may serve as a cue for the performance of nonreinforced
      peers.

PMID- 16795398
TI  - Naturalistic treatment of an autistic child.
AB  - The present research experimentally evaluated a "naturalistic" treatment program
      for an autistic child administered by the parents over a 2-yr period. Operant
      reinforcement techniques previously developed and tested in laboratory settings
      were initially assessed in a clinic and eventually in the family's home.
      Experimental manipulations were performed in both settings on rituals, crying and
      whining, compliance, non-verbal imitation, and verbal imitation. The results
      clearly indicated that parents can effectively treat autistic behaviors provided
      that they receive adequate training and supervision in operant reinforcement
      therapy, and provided that sufficiently potent reinforcers are available to
      maintain behavior.

PMID- 16795399
TI  - The effects of experimenter's instructions, feedback, and praise on teacher
      praise and student attending behavior.
AB  - Systematic use of experimenter's instructions, feedback, and feedback plus social
      praise was used to increase teacher praise for student attending behavior of
      three elementary school teachers. Experimenter's verbal interactions with
      teachers, teacher's verbal praise for student behaviors, and pupil attending
      behavior were recorded during baseline conditions. As the three successive
      experimental conditions were introduced first with Teacher A, then with Teacher
      B, in a multiple baseline design, behaviors of the experimenter, the two
      teachers, and eight students were measured and recorded. In the cases of Teachers
      A and B, experimental condition one (Instructions) and experimental condition two
      (Feedback) produced inconclusive results. Experimental condition three (Feedback
      Plus Social Praise) produced more teacher praise for student attending behavior.
      The entire "Package" of Experimenter's Instructions, Feedback, and Feedback Plus
      Social Praise was introduced to Teacher C in a single experimental condition. As
      in the cases of Teachers A and B, behaviors measured were: (1) the experimenter's
      verbal interactions, (2) the teacher's praise of students, and (3) the student's
      attending behavior. Introduction of the "Package" also produced more teacher
      praise for student attending behavior.

PMID- 16795400
TI  - Reinforced racial integration in the first grade: a study in generalization.
AB  - This study investigated possible factors in promoting racial integration, a
      matter of practical concern in schools today. Specifically, the effect of social
      and tangible reinforcement was studied on the social integration of five black
      children in a predominantly white classroom. "Sitting and seating with a new
      friend" in the school cafeteria was manipulated by (a) teacher directive combined
      with reinforcement and (b) by positive reinforcement alone. Treatment
      effectiveness was studied in the cafeteria and as generalization effects to a
      free-play period. The results indicated that reinforcement produced significant
      generalization to integrated free play, although intersubject variability was
      present. Evidence suggests that reinforcement techniques can be used effectively
      to promote social integration.

PMID- 16795401
TI  - Operant conditioning of human anal sphincter pressure.
AB  - Anal sphincter pressure in a 13-yr-old encopretic boy was modified by reinforcing
      increases in pressure exerted on a fluid-filled balloon inserted into the rectum.
      It was found that pressure changes were a function of the reinforcement schedule
      and that baseline levels (resting pressure) during extinction conditions tended
      to increase throughout the experiment.

PMID- 16795402
TI  - Social control of form diversity and the emergence of new forms in children's
      blockbuilding.
AB  - The blockbuilding behavior of three preschool girls was analyzed in terms of the
      forms manifest in any completed block construction, and found to contain few
      different forms in baseline sessions. Social reinforcement, given contingent on
      the production of any form not previously constructed within the current session
      (i.e., every first appearance of any form within a session was reinforced but no
      subsequent appearances of that form within that session were), increased the
      number of different forms built per sessions. Social reinforcement, given for all
      second and later appearances within the session, decreased the number of
      different forms built per session. Furthermore, it was found that new forms
      (forms never seen before in the child's total prior sequence of blockbuilding
      sessions) emerged at higher rates during periods of reinforcement of different
      forms (first appearances) than during periods of baseline or reinforcement of
      same forms (second and later appearances).

PMID- 16795403
TI  - An analysis of a token economy in stuttering therapy.
AB  - A stuttering therapy program in which adult stutterers were hospitalized and
      treated in small groups (n = 4) under token economy conditions is described. The
      Token System reinforced reductions and penalized increases in stuttering during
      conversation. The therapy program was divided into three stages. Initially,
      subjects were treated by the token system, which was then integrated with a
      delayed auditory feedback schedule designed to instate and shape a prolonged
      speech pattern into normal fluent speech. Finally, subjects passed through a
      speech situation hierarchy while under token control conditions. Experiments
      conducted in the first two stages of treatment are described. The first-stage
      experiments examined the design of the token system; the second-stage experiment
      assessed the effect of a contingent punishment schedule integrated with the
      delayed auditory feedback procedure in order to shape rate of speaking as well as
      fluency.

PMID- 16795404
TI  - A procedure for increasing oral reading rate in hard-of-hearing children.
AB  - This study investigated the effects of systematic training on the oral reading
      rate of four hard-of-hearing children. In training, systematic increases in
      pulsing rate of a vibrotactile stimulus were arranged. The children received
      points, exchangeable for money when their reading rate equalled the pulse rate of
      the stimulus. The training procedure was effective in increasing the oral reading
      rate in all children. Generalized increases in reading rate on untrained word
      lists, sentences, and paragraphs were also observed.

PMID- 16795406
TI  - Some effects of token rewards on school achievement of children with Down's
      syndrome.
AB  - The effectiveness of a token economy system in producing improvement in the
      academic performance of children with Down's syndrome was tested. One group of
      seven children received token reinforcement for correct responses and showed
      significant improvement both in arithmetic and language. A second matched group
      of six children received only verbal praise for correct responses to the same
      instructional materials and failed to improve in arithmetic but showed
      significant gains in language. Re-test scores one year later revealed that the
      Token Group maintained its gains in both subjects whereas the language
      performance of the No-Token Group showed a significant decline.

PMID- 16795405
TI  - Effects of reinforcement on children's academic behavior as a function of self
      determined and externally imposed contingencies.
AB  - This experiment was designed to compare the effects of contingent reinforcement
      under conditions of self-determined and externally imposed performance standards.
      A major purpose was to examine the maintenance of self-imposed performance
      standards over time. Children in one contingent reinforcement condition self
      determined their academic performance standards. The same performance standards
      were externally imposed upon children in a second contingent reinforcement
      condition who were yoked to subjects in the first condition. Children in a no
      reinforcement control condition performed in the absence of external reward.
      Behavioral productivity of the self-determination condition was greater than that
      of the no-reinforcement condition. Further, no attenuation of the efficacy of
      contingent reinforcement occurred when performance standards were self-determined
      rather than externally imposed. Over six sessions, children became progressively
      more lenient in their self-imposed performance demands in the absence of social
      surveillance.

PMID- 16795407
TI  - The analysis of performance criteria defining course grades as a determinant of
      college student academic performance.
AB  - A series of five experimental conditions were designed to investigate the
      influence of minimum performance criteria and grade labels on college student
      academic performance. A college course in abnormal psychology was taught in an
      individualized manner so that each student could perform on each unit of subject
      matter in individual performance sessions whenever he wished. In each of the five
      experiments the minimum performance criteria that had to be attained before
      progressing to the next unit were varied during the quarter and the resulting
      changes in performance were recorded. In Experiment I there were no criteria; in
      Experiments II, III, and IV three levels of criteria (High, Medium, and Low) were
      varied but all of the criteria defined a course grade of "A". In Experiment V,
      the three criteria defined course grades of A, B, and C. The results showed that
      the criteria controlled performance to a high degree, so that regardless of what
      quality of performance had been demonstrated previously or was being produced
      currently, performance was immediately changed to attain new criteria put into
      effect. Students in Experiment I produced very poor performance compared to the
      other conditions.

PMID- 16795408
TI  - The effects of contingent music on the intensity of noise in junior high home
      economics classes.
AB  - The effects of quiet-contingent music on the general noise levels of four seventh
      and eighth-grade classrooms were investigated. Following a baseline procedure,
      popular radio music was used to reinforce maintenance of noise below an
      acceptable level of intensity, 70 decibels, in three of the four classes. In the
      fourth class, a reversal design was used to show that the contingent presentation
      of the radio music was important to control the noise produced by the students.
      The teacher was free to engage in instructional activities because data
      collection and presentation of music were controlled by automatic apparatus.

PMID- 16795409
TI  - Self-evaluation by adolescents in a psychiatric hospital school token program.
AB  - Nine adolescent boys with a history of high rates of disruptive classroom
      behavior were selected from a psychiatric hospital school and placed in a
      remedial reading class after school in which various factors in a token
      reinforcement program involving self-evaluation were investigated. The effects of
      self-evaluation, in the form of a rating the students gave themselves about the
      appropriateness of their classroom behavior, were first assessed. While the
      students' ratings of their own behavior correlated highly with the teacher's
      ratings and evaluations made by independent observers, the self-evaluations did
      not lead to a reduction in disruptive behavior. A token reinforcement program, in
      which the teacher rated the students' level of appropriate behavior and in which
      the students traded earned rating points for prizes, clearly led to a reduction
      of disruptive behavior. When the students were given the opportunity to evaluate
      their own behavior and to receive rewards in exchange for the evaluation, they
      returned to their former rates of disruptive behavior.

PMID- 16795410
TI  - The development of instructional control over classroom activities of deviant
      preschool children.
AB  - Differential reinforcement of compliance with teacher invitations to complete a
      specific academic task was applied to three extremely negativistic children in a
      special preschool class. For each child, this technique resulted in clear and
      useful increases in compliance as it was applied. In addition, the technique
      produced a greater diversity of sampling the available tasks by all children,
      enabling them to contact instructional materials they had previously avoided. The
      reinforcement system, contingent access to free playtime, materials, and a snack,
      mediated by a token, was thus demonstrated to be an effective contingency. In the
      case of two children whose compliance was not maximized by differential
      reinforcement alone, further increases in compliance were produced by combining a
      1-min timeout for noncompliance with the differential reinforcement procedure.

PMID- 16795411
TI  - Development of syntax in a retarded girl using procedures of imitation,
      reinforcement, and modelling.
AB  - Three experiments demonstrated the development and generalized use of a singular
      and plural declarative sentence in a child initially lacking sentence form
      responses. In each experiment, an adult(s) served as a language model(s), and
      consequences (sweets) were provided for imitation of the model. During training
      trials, an item(s) was displayed first to the model(s) then to the subject; these
      displays were accompanied by requests to label the item(s). Generalization was
      assessed by a number of probe trials that were periodically interspersed among
      training trials. During these trials, the subject was requested to label the
      displayed item(s) without any preceding labelling response from the model. Using
      these procedures, generalized use of a singular sentence ("That is one-")
      resulted in Experiment I, and generalized use of a plural sentence ("These are
      two-") resulted in Experiment II. In Experiment III, two models (a singular and a
      plural sentence model) were made available to the subject but imitation of only
      one model was reinforced during any one condition. Results indicated the subject
      labelled probe (generalization) items with the same sentence form that was
      modelled and reinforced during training trials.

PMID- 16795413
TI  - Hiawatha designs an experiment.

PMID- 16795412
TI  - An analysis of individual differences in generalization between receptive and
      productive language in retarded children.
AB  - Retarded subjects were taught generative pluralization rules concurrently in both
      the receptive and productive modalities of language. Receptive training
      established correct pointing to either one or a pair of objects, in response to a
      spoken singular or plural label of the object(s); productive training established
      correct spoken labels of one or a pair of objects presented visually. However,
      these pluralization rules were established in each modality only for a specific
      class of plurals: those ending in -s for one modality, those ending in -es for
      the other modality. This training was successful in establishing generative, or
      rule-governed behaviors, such that untrained examples of singulars and plurals
      were usually responded to correctly. Nevertheless, despite this concurrent,
      generative behavior, probes revealed little generalization between modalities:
      three of four subjects did not generalize clearly from receptive training with
      one class of plurals to correct productive use of that class, nor did they
      generalize from productive training of the other class of plurals to correct
      receptive response to that class. The fourth subject, however, did show strong
      generalization of both these types. It was concluded that automatic
      generalization between receptive and productive language is not necessarily an
      inevitable result of language training in such subjects, and therefore may
      require explicit, if temporary, programming, such as by direct reinforcement.

PMID- 16795414
TI  - A system for recording individualized behavioral data in a token program.
AB  - A data matrix system used to record and summarize individual behavioral data is
      described. The major characteristics of the system are: (1) it provides a place
      to record and summarize all patient token exchanges, whether for standard
      contingencies or for idiosyncratic behavior; (2) it serves as a record and
      summary for time samples observed during a 24-hr period and as a record of
      reliability data on time sample measures; (3) it provides a place where the new
      token balance for each patient can be calculated and recorded for use the next
      day; (4) it provides for calculation of an individual patient's token balance at
      any given moment; and (5) it is a permanent record of each patient's daily
      participation in the program and documents progress in terms of his economic
      status as well as in changes in critical target behaviors.

PMID- 16795415
TI  - A coding procedure for teachers.
AB  - An observational technique for reliably estimating the per cent of time a student
      engages in appropriate and inappropriate classroom behavior is described. The
      regular classroom teacher can utilize the procedure without deviating from
      regular routine, and the obtained data can serve as a basis for dispensing token
      reinforcement.

PMID- 16795416
TI  - An experimental application of a social reinforcement approach to the problem of
      job-finding.
AB  - The current conception of the employment process is that positions become
      available, are publicized, and are filled by the most qualified job seekers. An
      alternative conception is proposed that social factors play a major role in the
      process and that job finding can be analyzed as an exchange of social reinforcers
      in which the first behavioral step is to locate job openings. A questionnaire
      survey of 120 jobs found that two-thirds of the job leads came from friends or
      relatives who: (1) usually knew of a specific opening (63%); (2) were themselves
      employed by the hiring firm (71%); and (3) actively influenced the hiring process
      (53%). An experimental evaluation was made of an "Information-Reward"
      advertisement procedure for motivating community residents to report unpublicized
      openings. It was found that the Information-Reward procedure produced 10 times as
      many job leads and eight times as many placements as a noreward control
      advertisement. These findings represent a first step toward a much needed
      technology of job finding that is based on experimental evidence and support the
      notion that the employment process depends on factors unrelated to work skills.

PMID- 16795417
TI  - Fading to increase heterosexual responsiveness in homosexuals.
AB  - Heterosexual responsiveness, measured by penile responses and reports of
      behavior, was strengthened in three homosexuals through a fading procedure. Using
      two slide projectors, colored slides of nude females were superimposed on colored
      slides of nude males. As the sexual response was emitted, the nude male was faded
      out and the nude female faded in. Heterosexual arousal decreased when the fading
      procedure was reversed or stopped and increased once again when fading was
      resumed. Homosexual arousal remained high during this experiment but had
      decreased in two subjects at follow-up. The results suggest that fading was
      responsible for altering stimulus control of sexual arousal and that aversive
      techniques may not be necessary in the treatment of sexual deviation.

PMID- 16795418
TI  - Prompting a consumer behavior for pollution control.
AB  - A field application of behavior modification studied the relative effectiveness
      of different prompting procedures for increasing the probability that customers
      entering a grocery store would select their soft drinks in returnable rather than
      nonreturnable containers. Six different 2-hr experimental conditions during which
      bottle purchases were recorded were (1) No Prompt (i.e., control), (2) one
      student gave incoming customers a handbill urging the purchase of soft drinks in
      returnable bottles, (3) distribution of the handbill by one student and public
      charting of each customer's bottle purchases by another student, (4) handbill
      distribution and charting by a five-member group, (5) handbills distributed and
      purchases charted by three females. The variant prompting techniques were equally
      effective, and in general increased the percentage of returnable-bottle customers
      by an average of 25%.

PMID- 16795419
TI  - Instrumental conditioning of diastolic blood pressure in essential hypertensive
      patients.
AB  - Eighteen male essential hypertensive patients participated in an experiment
      designed to compare two strategies for controlling high blood pressure. Each
      strategy was derived from the instrumental learning literature, and the aim was
      to treat the blood pressure response as an operant and determine the most
      effective conditioning procedure for manipulating it. The results demonstrate
      that patients could be conditioned to lower blood pressure by 20% to 30% over a
      period as brief as four days by providing an external signal and verbal praise
      contingent upon each reduction in diastolic pressure that met a pre-set
      criterion.

PMID- 16795420
TI  - Rewarding psychiatric aides for the behavioral improvement of assigned patients.
AB  - Different ways of modifying the aide-patient relationship to promote improvement
      in psychiatric patients were investigated. Psychiatric aides were given
      information about the behavior of assigned patients, cash awards based on the
      improvement of assigned patients, and different kinds of supervision by the
      psychology staff; the effects of these variables on a large number of
      psychiatrically relevant behaviors were measured. Appropriate behavior of
      patients increased when the aides were given quantitative information about the
      improvement of assigned patients. Cash awards for aides, which were not
      contingent on the behavior of patients had little effect, while cash awards
      contingent on the behavior of assigned patients were associated with more
      appropriate behavior. Direct supervision of aide-patient interactions was
      associated with an increase in appropriate behavior, while required consultation
      for the aides about assigned patients was not. Behavior of patients deteriorated
      when the program was terminated.

PMID- 16795421
TI  - Reinforcement and rate of litter depositing.
AB  - A study was conducted concerning the frequency of litter deposits in a single
      experimental trash receptacle located in a high-use, urban park setting. There
      were four two-week periods of alternating no-contingency, contingency conditions
      during which reinforcement and incentive were evaluated. It was found that
      reinforcement resulted in the highest rates of behavior and improvements in the
      aesthetic appearance of the area.

PMID- 16795422
TI  - Modification of nasal resonance in cleft-palate children by informative feedback.
AB  - Vibration of the walls of the nasal cavities during production of an English
      vowel or diphthong defined a hypernasal response. A crystal transducer on one
      side of the nose activated a voice-operated relay when vibration exceeded an
      arbitrary limit to provide an apparatus definition of the response. During
      training sessions, responses without nasal vibration turned on a white light in
      the sound-treated chamber. Subject 1 had a repaired cleft palate and mild
      hypernasal speech. Introduction of the differential feedback, reversal, and
      reinstatement of the feedback conditions resulted in a rapid decrease, increase,
      and decrease in percentage of nasalized productions of the /eI/ sound Subject 2
      had a cleft of the soft palate and severe hypernasal speech. Introduction of
      feedback produced a gradual decline in the percentage of hypernasal productions
      of the /##/ sound over 22 sessions. Removal and reinstatement of feedback
      resulted in a rapid increase and decrease respectively in the percentage of
      nasalized responses.

PMID- 16795423
TI  - Use and analysis of the "Good Behavior Game" to reduce disruptive classroom
      behavior.
AB  - A recent study reported procedures (the "good behavior game") for reducing
      disruptive classroom behavior. Replication of the procedures of the "good
      behavior game" in two classrooms showed it to be an effective technique for
      reducing disruptive talking and out-of-seat behavior. Further experimental
      analysis indicated that the effective components of the game were division of the
      class into teams, consequences for a team winning the game, and criteria set for
      winning the game. Although disruptive behavior was markedly reduced by the game,
      the reductions were correlated with only slightly improved accuracy of academic
      performance in the one classroom where academic performance was measured.

PMID- 16795424
TI  - Application of the Premack principle to the behavioral control of extremely
      inactive schizrophrenics.
AB  - The four most inactive schizophrenic patients were selected by an observational
      technique from a ward of severely ill chronic patients. Of the four, two patients
      repeatedly refused to accept any dispensable rewards. Applying Premack's
      principle of reinforcement, consistent work behavior was shaped and maintained,
      using sitting as the reinforcer. The results indicate that the strict application
      of Premack's principle may have considerable therapeutic potential for those
      patients who, by refusing all tangible rewards, fail to respond to a
      reinforcement regime.

PMID- 16795425
TI  - The modification of sentence structure and its relationship to subjective
      judgements of creativity in writing.
AB  - The present study objectively defined and manipulated some compositional
      variables in 10-sentence stories written by fourth-, fifth-, and sixth-grade
      students, and related these operationally defined variables to subjective
      judgements of creativity. Points, exchangeable for candy and extra recess, were
      given to members of two teams contingent upon their using different adjectives,
      different action verbs, and different sentence beginnings. The students' use of
      these selected parts of speech was modified and the independent subjective
      ratings indicated that stories written during contingency conditions were
      generally rated as more creative than those written during baseline conditions.
      Operational definitions that specify non-repetition or variety of responses, and
      contingencies that require response diversity may provide a beginning basis for
      defining writing creativity and the conditions that maximize its occurrence.

PMID- 16795426
TI  - The efficacy of stimulus fading and contingency management in the treatment of
      elective mutism: a case study.
AB  - Stimulus fading techniques were compared to those of contingency management in
      the treatment of a 6-yr-old, electively mute girl. Experimental periods consisted
      of the mother rewarding the child for verbal and motor responses to scheduled
      tasks, while a stranger slowly entered the room and then gradually administered
      the task items as mother left the room. A timeout contingency for non-response to
      task items was also employed. Control periods consisted of a stranger
      administering the same tasks to the child under the same contingencies but
      without the presence of the mother or the use of stimulus fading. Experimental
      and control periods were alternated during each treatment hour. The stimulus
      fading procedure was found to be a necessary component of the treatment process.
      While the timeout contingency for non-response was found to facilitate treatment
      if combined with stimulus fading, it was completely ineffective without the
      stimulus fading.

PMID- 16795427
TI  - Timeout as a punishing stimulus in continuous and intermittent schedules.
AB  - The effectiveness of a brief period of isolation (timeout) in the control of
      disruptive behavior emitted by a retarded child in a preschool classroom setting
      was examined. Timeout was shown to be an effective punishing stimulus, and its
      control of the child's disruptive behavior was investigated under four schedules
      of intermittent timeout. The results suggest that as a larger percentage of
      responses were punished, a greater decrease in the frequency of that response
      occurred. This inverse relationship between the percentage of responses punished
      and the frequency of the response did not appear to be linear, but rather a non
      linear function. This function suggests that some schedules of intermittent
      punishment may be as effective as continuous punishment, at least in the case of
      the continued suppression of a response that has already been reduced to a low
      frequency.

PMID- 16795428
TI  - Decreasing classroom misbehavior through the use of DRL schedules of
      reinforcement.
AB  - In three studies, reinforcing low rates of responding reduced inappropriate
      behaviors. In the first study, the talking-out behavior of one TMR student was
      reduced when the teacher allowed 5 min of free time for a talk-out rate less than
      0.06 per minute. In a second study, the talking-out behavior of an entire TMR
      class was reduced when reinforcement was delivered for a response rate less than
      0.10 per minute. In a third study, successively decreasing DRL limits were used
      to reduce off-task verbalizations of an entire high school business class. In
      each case, the DRL procedure proved manageable for the teacher and successful in
      reducing misbehavior.

PMID- 16795429
TI  - The comparative effectiveness of group and individually contingent free time with
      inner-city junior high school students.
AB  - A major purpose of the study was to assess the relative effects of group versus
      individually contingent free time in modifying student behaviors. Other purposes
      were to determine the effectiveness of well-planned lesson activities and tokens
      without back-up reinforcers. Eight students in an inner-city seventh-grade class
      of 32 blacks served as subjects. Well-organized lesson activities and success
      feedback via tokens did not produce high levels of desirable behavior. In
      contrast, group and individually contingent free time produced substantially
      higher levels of appropriate behavior than did the baseline conditions. The group
      reinforcement procedure appeared to be slightly more effective than individual
      reinforcement.

PMID- 16795430
TI  - Modification of deficits in reading for comprehension.
AB  - Subjects were asked to read a passage orally and then to answer questions about
      the passage. When praise and pennies were given for correct answers, the
      percentage of correct answers increased in two sixth-grade subjects whose reading
      for comprehension was tested to be 2 yr below grade level. The behavior of these
      subjects was compared to that of two subjects whose reading for comprehension was
      tested to be on grade level. Although no evidence for changes in the accuracy of
      answering comprehension questions is found in the previous literature, the
      percentage of correct answers in the children with deficits increased to
      approximately the same level as the children tested to be on grade level.

PMID- 16795431
TI  - Self-recording and student teacher supervision: variables within a token economy
      structure.
AB  - A token system was used to attempt to increase the accuracy with which special
      education students answered questions about reading assignments. In the token
      system, students recorded their own data, received toy money for accurately
      completing assignments, and were allowed to spend their toy money at the end of
      the week for educational activities. The accuracy with which students answered
      questions was higher when the token system was in effect than when it was not.
      When student teachers were used to manage the token system and when the self
      recording feature of the system was removed, only slight changes in the accuracy
      of the student performance were obtained.

PMID- 16795432
TI  - Development of verbal control over bizarre gestures of retardates through
      imitative and nonimitative reinforcement procedures.
AB  - Two retardates, manifesting hand gestures and minimal instructional control, were
      trained by imitative reinforcement procedures to imitate a response that was in
      contrast to gesturing. Next, with the contrast response continuing to be
      imitatively reinforced, gesturing was reduced by nonimitative reinforcement
      procedures; while providing facial and gesture cues, the adult said, "Do not do
      this". Imitative and nonimitative procedures were found to have the same effects
      on the contrast response as on the gesturing response, such that imitative
      procedures increased both responses, whereas nonimitative procedures decreased
      both. Nonperformance of gesturing was further maintained when (1) explicit verbal
      directions for nongesturing were superimposed upon the demonstrational-facial
      verbal cues as these collective stimuli were faded out and (2) food reinforcers
      for nongesturing were gradually removed while social consequences continued to be
      administered.

PMID- 16795433
TI  - Social punishment in the modification of a pre-school child's "autistic-like"
      behavior with a mother as therapist.
AB  - The mother of a 3-yr-old girl who showed "autistic-like" behavior was cued via an
      FM wireless microphone systematically to approve and disapprove of her child's
      behavior. After baselines were taken on two categories of problem behavior (Pre
      Academic and Social Behavior), the social contingencies were applied successively
      to each category. The Pre-Academic task was quickly established in the child when
      the mother applied these social contingencies. This result was replicated with
      requests for social interaction. In the final phase, cueing was withdrawn from
      both situations and the mother was able to maintain the child's improved
      behavior. An analysis of the mother's behavior suggested that her increased use
      of social punishment for inappropriate behavior was the key factor in the child's
      increasing responsiveness. Follow-up seven months later indicated that the
      improvements maintained.

PMID- 16795434
TI  - Overview of NIMH support of research in behavior therapy.
AB  - Many parts of the National Institute of Mental Health have explicit policies of
      encouraging research on behavior therapy. The policies about behavior therapy
      research of sub-units of NIMH are reviewed, as these policies existed in fiscal
      year 1973. Examples are given of the type of behavior therapy research that NIMH
      was supporting in 1972. Particularly important is the evaluation of the efficacy
      of behavior therapy in comparison with standard treatment procedures.

PMID- 16795435
TI  - Reviewer's Comments.

PMID- 16795437
TI  - Reviewers' comments.
AB  - The large number of nonexperimental manuscripts submitted to JABA and the lack of
      well-defined criteria for evaluating them, has necessitated formulation of a
      separate editorial policy (see policy statement on page 404 of this issue). The
      manuscript by Alan E. Kazdin was submitted before the policy concerning
      nonexperimental manuscripts went into effect and was reviewed by three
      established researchers who have made substantial methodological contributions to
      the field (Montrose M. Wolf, Murray Sidman, and L. Keith Miller were Reviewers A,
      B, and C, respectively). On the basis of the reviewers' comments, it was decided
      to publish the manuscript with only minor changes. However, because of the
      fundamental importance of many of the issues discussed in Kazdin's paper and
      because of the lack of clear agreement on some of these issues, as exemplified in
      the reviewers' comments, these comments are presented below.

PMID- 16795436
TI  - Methodological and assessment considerations in evaluating reinforcement programs
      in applied settings.
AB  - The extensive use of reinforcement programs in applied settings has led to
      experimentation that often fails to consider potential problems in design. The
      logic of the within-subject design is reviewed and specific designs employed in
      reinforcement programs are discussed. For each design (ABAB, or multiple-baseline
      design across behaviors, individuals, or situations), effects are discussed that
      make that design less powerful with respect to demonstrating the effect of the
      experimental variable. Problems in interpreting results of experiments in this
      area of inquiry are evaluated from the standpoint of internal and external
      validity. The issue of control groups is presented with considerations as to
      situations that require their use. Finally, the assessment strategy for
      evaluating operant programs is discussed and recommendations are made for
      measurement of behaviors in addition to the target response.

PMID- 16795438
TI  - A written exam procedure to minimize in-class cheating.

PMID- 16795439
TI  - Achievement Place: development of the elected manager system.
AB  - A series of experiments was carried out to compare several administrative systems
      at Achievement Place, a family style behavior modification program for pre
      delinquent boys. One aspect of the motivation system at Achievement Place was the
      token economy in which the youths could earn or lose points that could be
      exchanged for privileges. Several arrangements for assigning routine tasks and
      for providing token consequences for task performance were compared for their
      effectiveness in accomplishing the tasks and for their preference by the boys.
      The independent variables studied included: (1) individually assigned tasks
      versus group assigned tasks; (2) consequences for individual performance versus
      consequences for group performance; (3) a peer managership that could be earned
      by the highest bidder versus a peer managership that could be determined
      democratically by the peers. The results suggested that among those systems
      studied the system that best met the criteria of effectiveness and preference
      involved a democratically elected peer manager who had the authority both to give
      and to take away points for his peers' performances.

PMID- 16795440
TI  - Effects of bonuses for punctuality on the tardiness of industrial workers.
AB  - This study evaluated the effectiveness of an incentive procedure designed to
      increase the punctuality of six workers who were chronically late to work in a
      manufacturing company. The six workers in the experiment received a 2.00 pesos
      ($0.16 U.S.) bonus for every day that they arrived on time. A reversal design was
      used. The contingent bonuses increased the workers' rates of punctuality compared
      to their baseline rates. A control group of six workers observed during the same
      77-week period showed a trend toward decreasing punctuality. These results
      suggest that the use of small daily bonuses is a practical procedure for
      modifying chronic tardiness among industrial workers.

PMID- 16795441
TI  - The effects of play materials on social play.
AB  - To increase cooperative and social behaviors in children, contingency management
      programs have been successfully employed. This study examined the possibility
      that children's social behavior might also be significantly influenced by the
      nature of the available play materials. Children in an urban recreation center
      were systematically provided with toys designed for social or isolate play. It
      was found that social play occurred only 16% of the time when the children were
      provided with "isolate" toys, whereas social play occurred 78% of the time when
      children were provided with "social" toys. Thus, the selection of play materials
      should be an important consideration in any effort to teach children social
      behaviors.

PMID- 16795442
TI  - Positive reinforcement of litter removal in the natural environment.
AB  - Litter is an especially large and costly problem in unsupervised high-use
      recreational areas. This study investigated procedures to induce visitors to
      remove litter from an unsupervised U.S. Forest Service area in which signs
      attached to two litter stations instructed people to pick up and deposit litter.
      A small sum of money or chances on a larger sum given for participation usually
      resulted in more bags of litter being picked up per week. Although only a small
      proportion of the area's users participated in the project, ground surveys
      indicated the areas sampled were somewhat freer of litter during the payment
      condition. The results suggest that small monetary rewards may be a promising
      approach to litter control in unsupervised as well as supervised areas.

PMID- 16795443
TI  - Effects of peer tutoring and consequences on the math performance of elementary
      classroom students.
AB  - The effects of unstructured peer-tutoring procedures on the math performance of
      fourth- and fifth-grade students were investigated. Students' performances in two
      daily math sessions, during which they worked problems of the same type and
      difficulty, were compared. When students tutored each other over the same math
      problems as they subsequently worked, higher accuracies and rates of performance
      were associated with the tutored math sessions. The use of consequences for
      accurate performance seemed to enhance the effects of tutoring on accuracy. The
      results from an independent-study control condition, which was the same peer
      tutoring except that students did not interact with each other, suggested that
      interactions between students during the tutoring procedure were, in part,
      responsible for improved accuracy and rate of performance. When students tutored
      each other over different but related problems to those that they were
      subsequently asked to solve, accuracies and rates during tutored math sessions
      were also higher, suggesting the development of generalized skills in solving
      particular types of math problems.

PMID- 16795444
TI  - A comparison of two college classroom testing procedures: required remediation
      versus no remediation.
AB  - Forty one subjects from a 10-week introductory course in Educational Psychology
      were randomly divided into two experimental groups. All students took weekly
      quizzes over content material. Members of one group received little or no
      academic credit if they performed at less than 90% on a weekly quiz, but could
      earn additional credit by taking a weekly remedial quiz. Members of the second
      group also took the initial weekly quizzes, but retained their raw scores and
      were not permitted to take the weekly remedial quizzes. Performance on a 100-item
      multiple-choice comprehensive final revealed a statistically significant and
      educationally important difference between the two groups, the required
      remediation group scoring an average of one-half letter grade higher.

PMID- 16795445
TI  - Modification of interactive behaviors in chronic mental patients.
AB  - Four chronic mental patients, residents of a token economy treatment unit, were
      randomly assigned to an experimental or control condition and attended 10 thirty
      minute treatment sessions. For the two experimental subjects, contingent
      reinforcement was received for interacting with each other according to
      instructions in four distinct phases of interpersonal behavior: talking to
      another person, attending and talking to another person, asking and answering
      questions in a dyad, and working cooperatively in the dyad to solve problems. The
      two control subjects were instructed to perform the same behaviors but received
      non-contingent reinforcement. The results indicated a strong contingent
      reinforcement effect on the performance of the treatment sessions' target
      behaviors. Several baseline, treatment, and post-treatment response measures
      indicated that the treatment effects had generalized to other areas of social
      behavior away from the treatment setting.

PMID- 16795446
TI  - Increasing mentally retarded adolescents' verbalizations about current events.
AB  - The effects of antecedent and consequent events on the verbal behavior of three
      institutionalized mentally retarded adolescents were examined. Verbal statements,
      related to current national and international events, were recorded after
      exposures to television news programs. The study examined the accuracy of
      verbalizations as a function of: (1) exposures to television news presentations
      in massed (i.e., viewing the entire news program before an opportunity to
      describe it) versus distributed from (i.e., viewing each news item separately
      with each followed by an opportunity to describe it), and (2) contingent tokens
      and social praise for correct verbal responses (i.e., statements corresponding to
      news items presented). Both the temporal distribution of news presentations and
      the reinforcement procedures improved the accuracy of verbal statements emitted
      by the subjects.

PMID- 16795447
TI  - The effects of study questions and grades on student test performance in a
      college course.
AB  - Two experiments demonstrated the effects of study questions on student test
      performance in an introductory college course. Students in both experiments
      correctly answered study question items 20 to 30% more frequently than non-study
      question probes. Furthermore, mean performance on study question items was better
      than 90% during all phases of both experiments. The present experiments were also
      designed to study the effects of grades on test performance, and the relationship
      between long and short sets of study questions. The results of Experiment I
      clearly illustrated the importance of using grades to maintain high levels of
      student test performance. The results of Experiment II suggested that long sets
      of study questions may produce better performance on probe items than do short
      sets of study questions, but the effect was small.

PMID- 16795448
TI  - The effect of nonverbal teacher approval on student attentive behavior.
AB  - The effect of contingent nonverbal teacher approval on student attentive behavior
      was examined in a classroom with 12 retarded children. After baseline data were
      gathered on contingent verbal and nonverbal teacher approval and student
      attentive behavior, the teacher was instructed to increase her use of contingent
      nonverbal approval (smiles and physical contact) and to maintain her baseline
      level of verbal approval. After a reversal phase, the nonverbal approval phase
      was reinstated. Nonverbal teacher behaviors increased during the experimental
      phases, whereas verbal teacher approval (alone or in conjunction with nonverbal
      behaviors) did not increase. Attentive behavior increased for 11 of 12 students
      during the phases in which contingent nonverbal teacher approval increased.
      Correlational data suggested that nonverbal teacher approval accounted for
      behavior change of the students to a greater extent than did changes in the
      amount of teacher approval per se or in the teacher's use of verbal approval.

PMID- 16795449
TI  - Training two severely retarded adolescents to ask questions.
AB  - Two retarded boys were taught to discriminate items they knew how to label
      (training items) from items they did not know (probe items), to respond
      appropriately by naming any training items, and to ask a question about any probe
      items. The boys did not learn to question when appropriate questioning was
      modelled by the experimenter; however, when they were prompted and rewarded for
      asking questions about some training items, they then began asking questions
      about probe items. Both the modelling-and prompting-reinforcement procedures were
      introduced in an across-subject, multiple baseline design.

PMID- 16795450
TI  - Instruction-following behavior of a retarded child and its controlling stimuli.
AB  - A combination of positive reinforcement and fading of physical guidance was used
      to teach a profoundly retarded boy specific responses to specific verbal
      instructions. The design consisted of a multiple baseline of probe data across
      different verbal instructions. The subject started responding correctly to each
      verbal instruction as that item was trained in a multiple-baseline order.
      Generalization did not occur to items that had not yet been trained, nor did it
      occur to items included to assess generalization. Probes of variations in the
      verbal instructions, conducted after training was completed, revealed that
      generalization was minimal except in those cases where the variation consisted of
      the verb only, the noun only, the noun plus preposition, or where the verb of the
      instruction was presented last. Training a profoundly retarded 11-yr-old subject
      to respond to specific verbal instructions did not adequately facilitate the
      development of a generative instruction-following capability, nor did all verbal
      elements of the instruction control a specific response.

PMID- 16795451
TI  - The use of a "token helper" in the management of classroom behavior problems and
      in teacher training.
AB  - A grade-four class teacher was trained in the use of token and verbal
      reinforcement by an experienced "token helper", who demonstrated the procedures
      in the classroom. The introduction of a simple token system resulted in
      significant decreases in the disruptive behavior of 10 pupils in two morning
      periods. When the token helper withdrew from the classroom, the teacher managed
      the token system and maintained disruptive behavior at lower than baseline
      levels.

PMID- 16795452
TI  - Task analysis in curriculum design: a hierarchically sequenced introductory
      mathematics curriculum.
AB  - A method of systematic task analysis is applied to the problem of designing a
      sequence of learning objectives that will provide an optimal match for the
      child's natural sequence of acquisition of mathematical skills and concepts. The
      authors begin by proposing an operational definition of the number concept in the
      form of a set of behaviors which, taken together, permit the inference that the
      child has an abstract concept of "number". These are the "objectives" of the
      curriculum. Each behavior in the defining set is then subjected to an analysis
      that identifies hypothesized components of skilled performance and prerequisites
      for learning these components. On the basis of these analyses, specific sequences
      of learning objectives are proposed. The proposed sequences are hypothesized to
      be those that will best facilitate learning, by maximizing transfer from earlier
      to later objectives. Relevant literature on early learning and cognitive
      development is considered in conjunction with the analyses and the resulting
      sequences. The paper concludes with a discussion of the ways in which the
      curriculum can be implemented and studied in schools. Examples of data on
      individual children are presented, and the use of such data for improving the
      curriculum itself, as well as for examining the effects of other treatment
      variables, is considered.

PMID- 16795453
TI  - Reviewer's Comments.

PMID- 16795454
TI  - A note on the effects of saying grace on the behavior of an oppositional retarded
      boy.

PMID- 16795455
TI  - Assessing the effectiveness of programmed generalization.
AB  - Issues related to assessing change and retention of change were discussed. An
      alternative analysis was suggested for the data of a recent study by Walker and
      Buckley (1972). These authors had found that peer reprogramming, equating
      stimulus conditions, teacher training, and control groups maintained 77, 74, 69,
      and 67%, respectively, of appropriate behavior produced in a token economy. Their
      analysis made no use of baseline levels. Two analyses incorporating baseline
      scores were suggested. One involved change scores; the other, analysis of
      covariance using baselines as the covariate. Problems with the data made a clear
      preference difficult, but it was concluded that either analysis would have
      resulted in conclusions different from those of Walker and Buckley.

PMID- 16795456
TI  - Reviewers' comments.

PMID- 16795457
TI  - A procedure for concurrently measuring elapsed time and response frequency.

PMID- 16795458
TI  - Behavior encoder: a multi-movement, on-line behavior recorder.

PMID- 16795459
TI  - The effects of a token reinforcement procedure on bus ridership.
AB  - Tokens, exchangeable for a variety of back-up reinforcers, were delivered for
      several days to all persons boarding a clearly marked campus bus. This procedure
      increased ridership to 150% of baseline. The experiment was carried out to
      demonstrate the applicability of operant techniques to urban transportation
      problems. In this study, a token reinforcement procedure was introduced in an
      attempt to increase bus ridership while holding the costs of reinforcers to a
      minimum and circumventing the problems of individual satiety and preferences and
      of delivering cumbersome reinforcers. A methodology for establishing a token
      exchange procedure in an "open-field" behavior setting, where the subject
      population size, geographic location, preferences, age, sex, preferred hours of
      mobility, etc. are unspecified, is also presented.

PMID- 16795460
TI  - Training elementary aged peer behavior managers to control small group programmed
      mathematics.
AB  - The effects of a training procedure and two maintenance contingencies on
      consequence-dispensing behavior were investigated. Four peer behavior managers
      were trained to supervise small groups of subjects (four to six per group)
      working in programmed math materials and were compared with a teacher skilled in
      the use of social and point reinforcement and response cost. Manager training was
      differentially effective in accelerating manager's rates of appropriate social
      and point dispensing. Having manager reinforcement contingent upon manager
      consequence-dispensing resulted in moderately higher rates of appropriate social
      and point dispensing for three of four subjects than did having manager
      reinforcement contingent upon group study behavior. Two managers exposed to the
      group performance contingency before the manager performance contingency
      increased inappropriate social and point-dispensing behaviors to pretraining
      baseline levels. Subsequent change to the manager performance contingency was
      effective in reducing the inappropriate dispensing behavior of only one of the
      two managers.

PMID- 16795462
TI  - A note on the absence of a Santa Claus in any known ecosystem: a rejoinder to
      Willems.

PMID- 16795461
TI  - An investigation of the influence of student behavior on teacher behavior.
AB  - The relationship between student behavior change and teacher reactions to the
      change was investigated. One fifth-grade teacher served as the subject and two
      students in her class were employed as teacher change agents. In a multiple
      baseline design, the students' disruptive behavior (the independent variable) was
      modified without the teacher's knowledge. The teacher's reactions toward the
      students (the dependent variable) was monitored on several dimensions including:
      teacher behavior, teacher attitude toward students, and the quality of teacher
      verbal statements. Results indicated that student behavior change influenced the
      teacher's behavior. Implications are that students possess potent reinforcing
      properties for teachers and that students should be trained to be effective
      students.

PMID- 16795463
TI  - Technology and ecology: Reviewers' comments.

PMID- 16795464
TI  - Parental manipulation of child behavior in home observations.
AB  - The object of this study was to investigate the extent to which parents can
      manipulate their children's behavior in home observations. Twelve families with
      four- to six-year old children were recruited for the research. The parents were
      instructed to make their child look "bad" or "deviant" on three days of a six-day
      observation and to look "good" or "nondeviant" on alternate days. Results
      indicated that, as predicted, the rate of child deviant behavior, parental
      negative responding, and parental commands were all significantly higher on bad
      than good days. Parental responses to questionnaires provided more detailed
      information on how parents felt that they influenced their children in the
      desired directions. These results were discussed in terms of their implications
      for child psychopathology and the methodology of data collection in the natural
      environment.

PMID- 16795465
TI  - The length of teacher contacts and students' off-task behavior.
AB  - This study investigated the relationship between a teacher's contact durations
      and the off-task behavior of students not in contact with the teacher. Contact
      durations were defined as the amount of time the teacher spent working
      individually with each student. Off-task behavior was recorded for six third
      graders who comprised a small instructional group in mathematics. After baseline
      established that contact durations averaged approximately 38 sec, the teacher was
      instructed to hold contacts for at least 50 sec. During this phase, the students'
      off-task behavior increased. The teacher was then instructed to hold contacts for
      only 20 sec. During this phase, the students' off-task behavior decreased.

PMID- 16795466
TI  - The effects of mastery criteria and assignment length on college student test
      performance.
AB  - This study analyzed the function of two components of a personalized instruction
      course -mastery criteria for passing a test and assignment length. A high mastery
      criterion (100% correct) and short assignments produced better test performance
      than either a low mastery criterion (60% correct) or long assignments (four short
      assignments combined) on both study question items that students had in their
      possession and probe items that were not available to students in advance.

PMID- 16795467
TI  - The effects of principal-implemented techniques on the behavior of pupils.
AB  - Three investigations were conducted on the effects of various procedures
      initiated by a principal on the behavior of elementary school children. Seventy
      nine children including kindergarten, first, third, and fifth graders served as
      subjects. In Experiment I, when three chronically absent children attended
      school, the principal entered their classrooms and praised them for being
      present. In Experiment II, three low-achieving subjects were sent to the
      principal's office to receive praise contingent on meeting predetermined criteria
      in word-recognition and addition tutoring sessions. Experiment III assessed the
      effects that a procedure implemented by a principal had on the academic
      functioning of 74 third graders. Twice weekly in two classrooms the principal
      recognized both improving students and the highest performing students for their
      work on addition study sheets. In all three experiments, the target behaviors
      increased when the principal applied the treatment contingencies. The application
      of multiple baseline designs revealed a functional relationship between the
      children's behavior and the procedures implemented by the principal. Since the
      study was carried out in an overcrowded innercity public school, it was suggested
      that the treatment procedures might be widely applicable.

PMID- 16795468
TI  - A procedure for maintaining student progress in a personalized university course.
AB  - Ten students in a personalized university course were given target dates for
      completing each of 26 lessons. The lessons could be completed before those dates,
      but not after. The first two failures to complete a lesson by the target date led
      to "warnings"; the next failure required the student to withdraw from the course.
      When each student's rate of lesson completion was compared with and without
      target dates, it was found that students completed an average of 1.0 lesson a day
      with the target-date contingency and 0.3 without it. Individual data indicated
      that most students did few or no lessons without the contingency. It was
      concluded that a target-date contingency is an effective method for maintaining
      student progress in personalized university courses.

PMID- 16795469
TI  - Amount and distribution of study in a personalized instruction course and in a
      lecture course.
AB  - The rapid proliferation of courses based on Keller's Personalized System of
      Instruction (PSI) calls for a prompt evaluation of the relative costs involved in
      PSI and more traditional forms of college instruction. To determine the cost in
      student time required by a course taught with PSI relative to lecture, students
      did their studying in a special Study Center where course materials could be used
      but not removed. Students in the PSI section spent an average of about 50% more
      time in the Study Center (46 hr) than did students in the lecture section (30
      hr), but that difference was made up by the lecture students spending an average
      of 20 hr attending lectures. Thus, total preparation time was about the same. PSI
      students scored slightly higher on common course exams, and while college
      entrance exam scores correlated highly with course exam scores, Study Center time
      was reliably related to course exam score only for PSI students. An analysis of
      the study records of individual students revealed that PSI produced fairly
      regular patterns of study by all students, while lecture students varied greatly
      in their patterns.

PMID- 16795470
TI  - Anti-litter procedures in an urban high-density area.
AB  - In urban high-density areas, litter has become an increasingly obvious and
      pervasive problem. In the present study, repeated measures of the amount of
      litter on randomly selected yards in an urban low-income housing project were
      used to evaluate the effectiveness of a series of anti-litter procedures directed
      at the children residing in the project. Paying children for volume of trash
      collected resulted in only a small decrease in the number of litter pieces
      present. Paying them for cleaning assigned yards markedly decreased the level of
      litter in all sampled yards. Thus, children can be employed to maintain a clean
      neighborhood in spite of the rapid accumulation of new litter in urban yards.

PMID- 16795471
TI  - Recreation as a reinforcer: increasing membership and decreasing disruptions in
      an urban recreation centre.
AB  - It is presumed that recreation activities have a variety of functions for people,
      from tension reduction to citizenship development; however, a recreation
      activity's most empirically obvious function is as a reinforcer. This study
      demonstrates how two recurrent problems of urban recreation programs-recruitment
      of members and reduction of disruptive behaviors within the program-can be
      handled simply by contingently adjusting the amount of time the recreation
      activities are available. When extra time in the recreation center was provided
      to those youths who brought new members, dramatic increases in membership were
      achieved. On the other hand, when the closing time for each evening's recreation
      program was publicly moved forward by a few minutes for each offense, disruptive
      behaviors were nearly eliminated. Recreation used as a reinforcer can thus
      improve the basic operation of a recreation center and might similarly enhance
      other presumed and desired functions of recreation.

PMID- 16795472
TI  - Group contingencies for group consequences in classroom management: a further
      analysis.
AB  - The relative effects of rules, rules + feedback, and rules + feedback + group and
      individual consequences for appropriate behavior were investigated in three
      elementary classrooms during reading and mathematics periods. The consequences
      were individual and group praise, and group activities. The total intervention
      package (rules + feedback + group and individual consequences) was most effective
      in increasing appropriate behavior. Rules + feedback produced increased
      appropriate behavior in two of the three classrooms. Rules alone produced no
      change in classroom behavior. Maintenance of appropriate classroom behavior was
      noted approximately three weeks after the program ended. Teacher's correct use of
      praise was also maintained for two of the three teachers at levels generated
      during the total package condition.

PMID- 16795473
TI  - A quasi-experimental retrospective evaluation of a prison policy change.
AB  - Interrupted time-series design and quasi-experimental logic were employed to
      assess the behavioral effects of a prison disciplinary intervention on a
      population of approximately 2000 adult male inmates. The uncontrolled nature of
      the prison environment prevented experimental analysis of intervention effects.
      The quasi-experimental methodology applied in this study exemplifies how data,
      otherwise lost, can be retrieved. In addition, the process by which qualified
      conclusions can be drawn from the retrieved data is demonstrated.

PMID- 16795474
TI  - Reviewers' comments.

PMID- 16795475
TI  - The unsuccessful self-treatment of a case of "writer's block".

PMID- 16795476
TI  - Reviewer's Comments.

PMID- 16795477
TI  - A brief report on a device for unobstrusive visual recording.

PMID- 16795478
TI  - Homework assignments, consequences, and classroom performance in social studies
      and mathematics.
AB  - Elementary school students who frequently answered questions incorrectly in class
      were given daily homework assignments in social studies and math, but they rarely
      completed the assignments accurately and their classroom performance in social
      studies and math was only slightly better than when they did not have homework
      assignments. However, consequences provided for accurate completion of homework
      assignments increased the number of students completing homework and the accuracy
      with which homework assignments were completed. Further, assignments of homework
      with consequences for accuracy were associated with more accurate classroom
      performance.

PMID- 16795480
TI  - A brief report on a comparison of time-sampling procedures.

PMID- 16795481
TI  - Statistical inference for individual organism research: some reactions to a
      suggestion by Gentile, Roden, and Klein.

PMID- 16795479
TI  - The effects of explicit timing and feedback on compositional response rate in
      elementary school children.
AB  - The effects of several variables on compositional response rate were investigated
      in three classrooms. After establishing baseline composition rates in each of the
      three classrooms, an experimental phase was introduced that consisted of:
      explicit timing of the children's composition period with a stopwatch, immediate
      feedback on the number of words each child produced, public posting of the
      greatest number of words written by each child to date, and instructions to try
      to exceed their highest score. In the second-grade classroom, these conditions
      were introduced, removed, and re-introduced. In two fifth-grade classrooms, these
      conditions were introduced according to a multiple baseline, across classes. In
      all cases, introduction of the experimental conditions led to a doubling of rate
      of words written by students and an increase in subjective quality ratings of
      compositions made by independent judges.

PMID- 16795482
TI  - A further consideration in the application of an analysis-of-variance model for
      the intrasubject replication design.
AB  - It is argued that the analysis-of-variance model is inappropriate for assessing
      treatment effects in single-subject designs. In particular, such designs are
      demonstrated to violate the crucial assumption concerning the statistical
      independence of observations. Alternative methods of data analysis are suggested.

PMID- 16795483
TI  - Forcing square pegs into round holes: some comments on "an analysis-of-variance
      model for the intrasubject replication design".
AB  - This paper critically examines the application of fixed-effect one-way analysis
      of-variance procedures to learning data from a single subject. Procedures more
      appropriate for data obtained from intrasubject replication designs are briefly
      described.

PMID- 16795484
TI  - "An analysis-of-variance model for intrasubject replicaiton design": some
      additional comments.
AB  - The fixed effects ANOVA procedure utilized by Gentile, Roden, and Klein (1972)
      for single subjects is found inappropriate. Hartmann's proposal of a one-way
      fixed-effect ANOVA model is also considered. Time series analysis that takes
      serial correlation effects into account is recommended.

PMID- 16795485
TI  - Concerning the statistical procedures enumerated by Gentile et al.: another
      perspective.
AB  - The thrust of this paper is to bring to the attention of operant researchers
      statistical procedures that are appropriate for correlated data. In addition to
      specifying these statistical procedures consideration is given to the question of
      using individual comparison statistics rather than omnibus F tests. Specifically,
      it is recommended that a more powerful test of the experimental hypotheses can be
      obtained by performing Bonferroni t statistics rather than analysis of variance F
      tests.

PMID- 16795486
TI  - Statistical inference for individual organism research: mixed blessing or curse?
AB  - Descriptive and inferential statistics are described as judgemental aids, stimuli
      to which the scientist can more easily react than to his raw experimental
      results. The increasing emphasis on the significance test as the main judgemental
      aid utilized in experimental psychology is credited with several harmful effects
      on experimental practice. The area known as "the experimental analysis of
      behavior" has so far escaped most of these harmful effects, but now we see an
      increased interest in the development of appropriate significance tests for
      individual organism research. This interest is based on the view that it is not
      possible to effect adequate levels of experimental control with much human
      applied research, and that in such cases a significance test would be quite
      valuable as a judgemental aid, both of which points are considered to be
      essentially incorrect, and if accepted, potentially harmful.

PMID- 16795487
TI  - A brief research report on accuracy and academic performance.

PMID- 16795488
TI  - Shaping data collection congruent with experimental hypotheses.
AB  - The influence of instructions and feedback from an experimenter on observational
      recordings of disruptive behavior was evaluated. Four subject-observers recorded
      four categories of disruptive behavior from videotapes of children in a classroom
      setting. Two sets of videotapes, labelled "baseline" and "treatment", were
      matched for rates of disruptive behavior in each category. The observers were
      told that two target behaviors were expected to decrease and the other two
      control behaviors were not expected to change during the treatment condition.
      During observational recording of treatment videotapes, the observers were given
      positive feedback when they reported decreases in the two target behaviors, and
      negative feedback when they reported either to change or increases in the two
      control behaviors. The target behaviors were recorded less frequently by
      observers, while recordings of control behaviors were unaffected during the
      treatment phase. These results suggest that contingent feedback to observers
      should be avoided as a possible source of bias in behavioral recordings.

PMID- 16795489
TI  - A classroom program teaching disadvantaged youths to write biographic
      information.
AB  - Little attention has been given to how formal classroom instruction can be
      adapted to teach youths everyday skills such as the correct writing of biographic
      information frequently requested in transactions like applying for a job or a
      social security number and cashing a check. In this study, six youths in a
      special education classroom were taught to complete job application forms with
      the date, their name, signature, address, telephone number, date of birth, and a
      reference's name, address, and occupation. Each youth was trained on one item of
      biographic information at a time, after which he was tested on four application
      forms, including one on which he had not been trained. The tests show that after
      an item had been taught, it was correctly used in completing application forms on
      which the youths had been trained and forms on which they had never been trained.
      The study demonstrates the feasibility of teaching community-living, vocation
      related skills to special-education youths in a classroom setting.

PMID- 16795490
TI  - Training public-speaking behavior: an experimental analysis and social
      validation.
AB  - The effect of an instructional package on public-speaking behaviors was analyzed
      in two experiments. The instructional package was designed to teach public
      speaking trainees to look at the audience, make gestures, and perform a number of
      speaking behaviors. The results of Experiment I, with a university student
      serving as the trainee, showed that the percentage of each category of public
      speaking target behavior increased only after the instructional package was
      introduced for that category. The results of Experiment 2, with three low-income
      paraprofessional staff members of a neighborhood service center serving as
      trainees, showed that the percentage of target behaviors increased after the
      instructional package was introduced for the respective trainee. Audience ratings
      of public-speaking performance were correlated with direct observations of target
      responses. All trainees showed marked improvements in audience ratings from
      pretraining to posttraining. This study demonstrated an effective procedure for
      training public-speaking behaviors.

PMID- 16795491
TI  - Behavioral community psychology: training a community board to problem solve.
AB  - This study demonstrated the effect of training nine lower socio-economic adults
      participating as policy board members in a federally funded rural community
      project to make behaviorally defined statements to increase problem-solving
      behaviors in board meetings. A multiple-baseline design across subjects and
      skills was used to analyze the behavioral categories of: (1) stating the problem;
      (2) finding solutions to the problem, and (3) implementing the action to the
      solution. Problem-solving responses during board meetings increased for subjects
      following training and remained higher than baseline during follow-up.

PMID- 16795492
TI  - Reactivity to home observation: a comparison of audio recorded behavior with
      observers present or absent.
AB  - THE STUDY COMPARED THE BEHAVIOR OF FAMILY MEMBERS AT HOME AS RECORDED BY
      AUDIOTAPE RECORDINGS IN TWO CONDITIONS: with an observer present or absent.
      Behavioral differences were expected as a function of differential reactivity to
      these observational procedures, but none was found, and there was no evidence of
      adaptation effects in either condition. In general, significant positive
      correlations were obtained between the rates of recorded behavior in both
      situations. The implications of these findings for the development of nonreactive
      observation procedures were discussed.

PMID- 16795493
TI  - Does use of tangible rewards with individual children affect peer observers?
AB  - The common assumption that employing tangible rewards with individual children
      will have adverse effects upon peer observers was studied in the preschool
      setting. Multiple-subject, multiple-baseline procedures were applied to two
      classes of children, aged 3.5 to 6 yr. In each group, three consecutive children
      with low base rates of in-seat behavior received a verbal contingency and food
      rewards for sitting, while peers (with either low or high rates of in-seat
      behavior) received neither food nor teacher attention for sitting. Peer reactions
      measured were in-seat behavior, aggression, nonaggressive disruptive behavior,
      and complaints. The procedures neither decreased the in-seat behavior of peer
      observers, nor increased their aggressive or disruptive behavior. On the
      contrary, peers with low base rates of sitting initially displayed an abrupt, but
      temporary, increase in sitting. Moreover, although no compensatory attention was
      delivered, all children exhibited improved sitting by the end of the study.
      Complaints, which consisted mainly of requests for rewards, decreased in
      frequency with successive program phases, and within each phase. It is suggested
      that the class improvement in sitting behavior and the absence of negative
      effects on observers may be partially due to the high frequency of attention the
      teacher maintained for other desired behavior and the lack of attention to
      children's complaints.

PMID- 16795495
TI  - Communication.

PMID- 16795496
TI  - Measuring urban problems: a brief report on rating grass coverage.

PMID- 16795494
TI  - Effects of an audio cueing system on the rate of teacher praise.
AB  - The effects of automated cueing on teacher praise rate was investigated in one
      special, one fourth-, and one seventh-grade classroom. After establishing
      baseline praise rates in each of the three classrooms, two methods for increasing
      teacher praise rate were introduced according to a multiple-baseline design.
      During the first phase, two teachers were instructed to count and graph their
      praise rate during each session. All teachers received auditory cues to prompt
      praising during another phase. In all cases, introduction of cues markedly
      increased teacher praise rates, but self-recording was relatively ineffective. An
      analysis of teacher-praise distributions showed that cues closely controlled
      teacher praise for two of the three teachers.

PMID- 16795497
TI  - A neglected literature and an aphorism.

PMID- 16795498
TI  - Generalization of teacher behavior as a function of subject matter specific
      discrimination training.
AB  - The effect of training on the rate of behavior-specific praise for two fourth
      grade teachers was investigated within a multiple-baseline design. Training
      teachers to identify instances of behavior-specific praise on videotaped
      presentations (discrimination training) combined with instructions to use praise,
      and audiotape recordings of the teachers' classroom interactions as feedback,
      increased the rates of behavior-specific praise. However, the effects were
      restricted to subject-matter areas in which training was conducted.

PMID- 16795499
TI  - A brief report clarifying the effects of distributional shifts on standardized
      test statistics.

PMID- 16795500
TI  - Social evaluation research: the evaluation of two police patrolling strategies.
AB  - In most social evaluation research it is difficult to achieve the degree of
      experimental rigor possible in an applied behavioral study. This study
      illustrates how the evaluation researcher can increase experimental rigor in the
      analysis of social interventions. In the first evaluation, a variation of the
      time-series design that offered maximum experimental control given the
      limitations of the situation, was employed to evaluate the effects of a
      specialized home-burglary police patrol. This design revealed that no effects
      could be attributed to the patrol. In the second evaluation, a multiple baseline
      like design was possible in determining the effects of a police walking patrol.
      This design revealed that the patrol produced an increase in crime reporting but
      not in arrests. Social interventions often occur in a manner that allows varying
      degrees of experimental analysis. The evaluation researcher must attain optimal
      experimental analysis given the limitations of each social intervention.

PMID- 16795501
TI  - Natural rates of teacher approval and disapproval in the classroom.
AB  - Sixteen classroom observational studies were conducted to determine natural rates
      of teacher verbal approval and disapproval in the classroom. Rates of teacher
      verbal approval and disapproval were measured by the Teacher Approval and
      Disapproval Observation Record (TAD) over Grades 1 through 12. Teacher verbal
      approval rates dropped over grade, with a marked drop after second grade. In
      every grade after second, the rate of teacher verbal disapproval exceeded the
      rate of teacher verbal approval. These rates are interpreted in terms of
      reinforcement theory.

PMID- 16795502
TI  - Effects of implementing a token economy on teacher attending behavior.
AB  - After systematic attempts to increase a teacher's positive responding to her
      first-grade students, a token-economy system was implemented as a "last resort".
      On-task student behavior and relative frequency of positive and negative teacher
      comments were systematically observed. Data indicated that institution of the
      token system was associated with a relatively higher percentage of positive than
      negative comments. Termination and re-implementation of the token system caused
      reversals of the teacher's behavior.

PMID- 16795503
TI  - The marked item technique: a practical procedure for litter control.
AB  - Unobtrusively marked items of litter were placed among existing trash on the
      grounds of a federal youth correctional facility. Inmates voluntarily collected
      trash and deposited it at a central location, where they were given money or
      special privileges for each piece of marked litter found. A multiple-baseline
      design with litter counts in three areas revealed successive reductions of 55%,
      88%, and 71% after 17, 22, and 36 days of baseline, respectively. A fourth area
      served as a baseline-only control, and revealed no systematic changes. Advantages
      of the procedure over previously devised techniques were discussed and
      applications in other areas of pollution control suggested.

PMID- 16795504
TI  - Behavioral self-management in story writing with elementary school children.
AB  - The effect of self-management procedures on objective writing responses and on
      the subjectively assessed quality of children's writing was investigated. All
      experimental procedures were applied to each of the 37 children in a regular
      Grade 3 class, and 14 of these children were randomly selected for data
      collection. Following baseline conditions, self-assessment plus self-recording of
      writing responses was introduced. This did not increase the number of sentences,
      number of different action words, or number of different describing words, or
      improve the quality of the stories. Self-determined and self-administered
      reinforcement was added to the self-assessment and self-recording procedures
      contingent on each of the writing responses in turn. Rates of responding were
      substantially increased and the stories received higher subjective ratings of
      quality from two independent judges. An increase in on-task behavior was
      correlated with self-reinforcement of writing responses.

PMID- 16795505
TI  - Primes, contingent attention, and training: effects on a child's motor behavior.
AB  - The use of primes, contingent attention, and training sessions to assess a
      child's engagement and skill in six large motor activities was examined using a
      combination reversal and multiple-baseline design. Assessment was based on four
      levels: proximity to equipment, touching equipment, unskilled participation, and
      skilled participation. Before training, priming (suggestion to the child) was
      more effective than contingent attention for increasing the subject's engagement
      (but not skill) in five activities and for increasing skilled participation in
      one activity. Training of four activities in the natural environment effectively
      increased the subject's skill level in five activities. Thus, training appeared
      to generalize to one of these five activities in this setting and also to
      skillfully executed stair climbing in an adjoining setting. After training,
      primes and contingent attention were sufficient to maintain both the subject's
      skill level and engagement in all activities. Postchecks in the same setting the
      following semester with different teachers revealed only slight increases in
      participation, as compared to previous baselines, but all participation was at
      the skilled level. Social interaction, which was not experimentally manipulated,
      did not systematically vary in relation to changes in experimental conditions.

PMID- 16795506
TI  - Incidental teaching of language in the preschool.
AB  - "Incidental teaching" denotes a process whereby language skills of labelling and
      describing are learned in naturally occurring adult-child interactions. In the
      present study, 15-min daily samples of the spontaneous speech of 11 children were
      recorded during free play over eight months of preschool. After incidental
      teaching of compound sentences, increases in unprompted use of compound sentences
      were seen for all the children, first directed to teachers, and then to children,
      in accordance with who attended to the children's requests for play materials.
      The incidental teaching procedure also stimulated spontaneous variety in speech,
      and appears to have general applicability to child learning settings.

PMID- 16795507
TI  - Role playing to train elementary teachers to use a classroom management "skill
      package".
AB  - Two teachers who led regular third-grade classrooms in a suburban elementary
      school were trained via role-playing to use a broad range of social skills in
      dealing with group behavioral management in the classroom. Teacher training
      reduced disruptive student behavior during both seat work and group discussions
      in both classrooms. A measure of student productivity during arithmetic period in
      one classroom showed significant gains in arithmetic problems correct per day for
      the middle and bottom thirds of the class, with the bottom third increasing by
      76%.

PMID- 16795508
TI  - An analysis of a performance feedback system: the effects of timing and feedback,
      public posting, and praise upon academic performance and peer interaction.
AB  - In the first experiment, after establishing baseline composition rates in each
      classroom, timing (announcing time limits) and feedback (student self-scoring)
      were introduced followed by the introduction, removal, and reintroduction of
      public posting of highest scores. Timing and feedback improved story writing
      performance and public posting of highest scores improved performance even
      further in both classrooms. Teacher praise produced further improvement in one
      classroom but had no effect on performance in the other. Changes in on-task
      behavior paralleled changes in writing rate. Comments made by children concerning
      their own work or work of their peers were recorded throughout the experiment.
      Although the baseline rate of performance comments was almost zero, the
      introduction of each variable markedly increased the rate of performance
      comments. In the second experiment, baseline rates on reading and language
      exercises were established in a fifth-grade classroom. The entire performance
      feedback system was introduced on a multiple baseline across the two behaviors
      and then removed during the final phase of the experiment. Introducing the system
      improved performance on both tasks. These results further increased the
      generality of some of the findings of the previous experiment and of previous
      research on the efficacy of the experimental package of timing, feedback, public
      posting, and praise.

PMID- 16795509
TI  - An evaluation of time-sample measures of behavior.
AB  - Continuous and time-sample measures of the in-seat behavior of a secretary were
      obtained. Measurement error, i.e., the extent to which the sample measures
      deviated from the continuous measure, was a function of the frequency of the
      sample measurements and the criterion used to score an example of the behavior.
      If the behavior had to be exhibited throughout the observational interval (whole
      interval time sampling), there was a consistent underestimate of the continuous
      measure. If the behavior had to be exhibited only briefly within the
      observational interval (partial-interval time sampling), there was a consistent
      overestimate of the continuous measure. And, if the behavior had to be exhibited
      at the end of the observational interval (momentary time sampling),
      overestimations and underestimations of the continuous measure occurred about
      equally often. As expected, the more frequently the sample measures were made the
      closer was the agreement between the sample and continuous measures. Two
      conclusions concerning measurement error in interval time sampling were made. The
      first was that the error will be a function of the mean time per response. The
      second is that this error will not be consistent across experimental conditions.

PMID- 16795510
TI  - Clowning around to stop clowning around: a brief report on an automated approach
      to monitor, record, and control classroom noise.

PMID- 16795511
TI  - Digitek coding and computer analysis of behavior observation data.

PMID- 16795512
TI  - Differences among common methods for calculating interobserver agreement.

PMID- 16795513
TI  - A behavioral analysis of peaking in residential electrical-energy consumers.
AB  - This study was concerned with "peaking", which is the tendency for electrical
      energy users to consume at high rates for brief periods during the day. Peaking
      results in the inefficient use of generating facilities, which may lead to
      unfavorable effects on the environment, such as the construction of new energy
      producing facilities or the activation of older, less safe, generating units. A
      continuous data collection system to monitor consumption of electrical energy was
      installed in the homes of three volunteer families. Information, feedback, and
      incentives were evaluated for their effects on peak energy consumption. A
      combination of feedback plus incentives was most effective and reduced peaking
      about 50%. Removal of experimental treatments resulted in a return to pre
      treatment patterns of consumption.

PMID- 16795514
TI  - The effects of primary reward on the I.Q. performance of grade-school children as
      a function of initial I.Q. level.
AB  - The effect of candy reward on I.Q. scores was investigated in 72 first- and
      second-grade children. All subjects were administered Form A of the Peabody
      Picture Vocabulary Test and, based upon these scores, were divided into three
      blocks: low, middle, and high. From each block, subjects were randomly assigned
      to one of three conditions (contingent reward, noncontingent reward, or no
      reward) that were in effect during administration of Form B. Results showed that
      candy given contingent upon each correct response increased I.Q. scores for the
      initially low scoring subjects, but had no influence on the scores of middle and
      high scoring subjects.

PMID- 16795515
TI  - Effects of group response-cost procedures on cash shortages in a small business.
AB  - The effect of a group response-cost procedure (accompanied by verbal and written
      instruction) designed to decrease cash shortages in a small business was
      evaluated with a reversal design. When cash shortages were subtracted from the
      six employees' salaries on days in which the shortage exceeded 1% of total daily
      sales, the magnitude of daily shortages sharply decreased. This response-cost
      contingency was used only three times throughout the study, with a maximum cost
      of $8.70 per subject over the 41-day period. The efficacy of the procedures may
      be due to either increased precision in change calculations, a decreased
      frequency of stealing from the cash register, increased shortchanging of
      customers, and/or increased incidents of register under-ringing. Ethical
      questions relative to the utilization of group punishment procedures are raised,
      and it was concluded that the procedures used were more humane than commonly used
      alternatives.

PMID- 16795516
TI  - Developing positive social-emotional behaviors: a study of training and
      generalization effects.
AB  - Four handicapped children were taught four positive social-emotional behaviors:
      smiling, sharing, positive physical contacting, and verbal complimenting, using
      instructions, modelling, and praise. Rates of these behaviors were shown to
      increase in four trained subjects using a within-subject multiple-baseline
      experimental design. The generality of the behavior change was investigated by
      integrating three untrained subjects with the trained subjects in a setting free
      of adult-imposed contingencies and through a series of follow-up observations.
      Three trained subjects evidenced collateral increases in the generalization
      setting on at least one other behavior when training in smiling was conducted.
      One trained subject showed generalization session increases for each behavior
      when training was conducted to increase that behavior. All three untrained
      subjects demonstrated increased rates of smiling and sharing when interventions
      were conducted to increase those behaviors with the trained subjects. There was
      no appreciable generalization of verbal complimenting by either the trained or
      the untrained subjects. Both trained and untrained subjects generally maintained
      their increased rates of smiling, sharing, and positive physical contacting
      across four weeks of follow-up observations.

PMID- 16795517
TI  - The social validation and training of conversational skills.
AB  - Three reliably measured components of conversation-questioning, providing
      positive feedback, and proportion of time spent talking-were identified and
      validated as to their social importance. The social validity of the three
      conversational behaviors was established with five female university students and
      five female junior-high students. Each was videotaped in conversations with
      previously unknown adults. The conversational ability of each girl was evaluated
      by a group of 13 adult judges who viewed each tape and rated each conversant
      "poor" to "excellent" on a seven-point rating scale. The average ratings of the
      girls correlated at r = 0.85 with the specified behavioral measures. These
      procedures were replicated with additional subjects and judges and yielded a
      correlation of r = 0.84. The high correlations between ratings and the objective
      measures suggested that the specified conversational behaviors were socially
      important aspects of conversational ability. Employing a multiple-baseline design
      across the behaviors of asking questions and providing positive feedback, an
      attempt was made to train four girls who used these behaviors minimally to engage
      in the behaviors in conversations with adults. Adult judges were again employed
      to rate randomly selected samples of the girls' skills in pre- and posttraining
      conversations. The average ratings of the girls before training were lower than
      both the university girls and the junior high-school girls. After training, the
      girls' conversational abilities were rated substantially higher than those of
      their junior high-school peers. These rating data validated the benefits of the
      training and the social importance of the behavioral components of questions and
      feedback in conversation. The authors suggest that it may be necessary for
      traditional behavior analysis measurement systems to be supplemented by social
      validation procedures in order to establish the relationship between
      "objectively" measured behaviors and complex classes of behavior of interest to
      society.

PMID- 16795518
TI  - Decreasing fuel-oil consumption through feedback and social commendation.
AB  - The energy crisis of the winter of 1973-74 led to severe shortages of fuel oil
      for home heating and a government request for voluntary conservation by the oil
      consumer. This experiment tested two methods of facilitating fuel-oil
      conservation. Home fuel-oil consumers were randomly assigned to one of three
      experimental groups: feedback of information on rate of oil use, feedback plus
      commendation for reduced consumption, or a no-treatment control. The consumption
      rate for the feedback plus commendation group was significantly lower than that
      of either the informational feedback group or the control group. The
      informational feedback group did not differ from the control group. The results
      suggest that feedback alone may not result in oil conservation, but that feedback
      combined with commendation can produce socially significant savings.

PMID- 16795519
TI  - Use of normative peer data as a standard for evaluating classroom treatment
      effects.
AB  - This study illustrated the use of normative behavioral observation data as a
      standard for evaluating the practicality of treatment effects produced in other
      settings. Three groups of eight subjects each, displaying relatively low
      proportions of appropriate classroom behavior when compared with regular
      classroom peers, were selected for treatment within an experimental classroom
      setting. The three groups were exposed to intervention procedures designed to
      reinforce either direct academic performance and/or facilitative nonacademic
      classroom responses. The treatment was effective in changing levels of
      appropriate behavior (1) above baseline levels in the experimental classroom, and
      (2) to within normal peer-defined limits when reintegrated into the regular
      classroom. Further, the data reflect successful maintenance of these effects for
      a seven- to 12-week follow-up period. Several applications of a normative model
      for evaluating treatment, generalization, and maintenance effects were presented
      and discussed.

PMID- 16795520
TI  - Peer and college-student tutoring as reinforcement in a token economy.
AB  - Eighteen second-grade children initially received feedback in the form of
      nonredeemable tokens for reducing their disruptive classroom behavior. Four types
      of tutoring were then introduced in a Latin Square Design: noncontingent tutoring
      from fifth-grade peers, contingent peer tutoring, noncontingent college tutoring,
      and contingent college tutoring. No significant difference was found in the level
      of disruptive behavior of those children tutored by fifth-grade peers or college
      students, but contingent tutoring was significantly effective in reducing
      disruptive classroom behavior.

PMID- 16795521
TI  - Effects of two teacher-presentation rates on off-task behavior, answering
      correctly, and participation.
AB  - Off-task behavior, correct answering, and participation during beginning reading
      instruction were recorded for two low-achieving first-grade children during two
      different rates of teacher presentation. A slow-rate presentation (A) was
      compared with a fast-rate presentation (B) in an ABABAB design. In slow-rate
      presentation, there was a delay between the children's response and introduction
      of the next task. In fast-rate presentation, there was no delay. A new teacher
      taught during the final AB phases, which allowed for a brief replication. Both
      teachers were reminded on a fixed-interval 90-sec schedule throughout all phases
      of the experiment to praise the subjects, thus preventing a confounding of social
      praise and rate of teacher presentation. Fast-rate presentation was accompanied
      by a lower per cent occurrence of off-task behavior for both Subjects 1 and 2.
      For Subject 1, correct answering and participation were more frequent during all
      three fast-rate phases. For Subject 2, correct answering and participation were
      more frequent during the fast-rate phases after the first reversal.

PMID- 16795522
TI  - Evaluation of family intervention through unobtrusive audio recordings:
      experiences in "bugging" children.
AB  - Five children referred to a child-family intervention program wore a radio
      transmitter in the home during pre-intervention and termination assessments. The
      transmitter broadcast to a receiver-recording apparatus in the home (either
      activated by an interval timer at predetermined "random" times or by parents at
      predetermined "picked" times). "Picked" times were parent-selected situations
      during which problems typically occurred (e.g., bedtime). Parents activated the
      recorder regularly whether or not problems occurred. Child-deviant, parent
      negative, and parent-commanding behaviors were significantly higher at the picked
      times during pretest than at random times. At posttest, behaviors in all three
      classes were substantially reduced at picked times, but not at random times. For
      individual subject data, reductions occurred in at least two of the three
      dependent variables for three of the five cases during random time assessments.
      In general, the behavioral outcome data corresponded to parent-attitude reports
      and parent-collected observation data.

PMID- 16795523
TI  - The effects of individual and group consequences on school attendance and curfew
      violations with predelinquent adolescents.

PMID- 16795524
TI  - The effects of explicit timing on math performance.

PMID- 16795525
TI  - The measurement of manuscript letter strokes.

PMID- 16795526
TI  - The design and evaluation of a worksharing system for experimental group living.
AB  - Failure to share household chores equitably may be a major cause of the high
      failure rate of experimental group-living arrangements. A behavioral approach to
      worksharing based on a point system was implemented in one experimental group and
      its most important components experimentally evaluated. Experiment I showed that
      awarding credits produced more work than not awarding credits. Experiment II
      showed that making credits contingent on the outcome of a detailed inspection
      produced more work than awarding credits noncontingently. Experiment III
      demonstrated that awarding rent reductions contingent on credit earnings produced
      more work than awarding rent reductions noncontingently. Other evaluative data
      suggest that the resulting living arrangement is cheaper, more effective, and
      more satisfactory to the residents when compared to the most popular alternative
      living arrangements.

PMID- 16795527
TI  - A behavioral technology for producing concept formation in university students.
AB  - Three experiments analyzed the effectiveness of a textbook incorporating "concept
      programming" in producing concept formation in university students. The concept
      programming portion of each lesson requires students to determine which concept
      is illustrated by each of 20 short fictional stories about everyday behavioral
      situations. The stories are selected to illustrate and contrast the concepts of
      that lesson. Student responses are heavily prompted during the initial stories of
      each lesson. The first experiment demonstrated that students generalize to
      entirely novel examples from the examples in the textbook. The second experiment
      demonstrated that the concept programming portion of the textbook is a critical
      component in producing generalization. The third experiment demonstrated that the
      amount of concept formation produced by the concept programmed textbook is
      greater than that produced by a widely used standard textbook.

PMID- 16795528
TI  - Facilitating paper recycling: effects of prompts, raffles, and contests.
AB  - The effects of prompts and reinforcement to promote paper recycling were compared
      in six university dormitories. For a Prompt condition, residents were urged to
      recycle paper for ecological reasons via flyers distributed to each room. For a
      Raffle contingency, residents were given one raffle ticket for every pound of
      paper brought to a collection center. For a Contest contingency, two dorms were
      paired and the dorm whose residents delivered the most paper won $15 for its
      treasury. Contingency awareness was strengthened via a flyer placed under the
      door of each resident's room. Flyers alone had little effect in increasing paper
      recycling behaviors, but the raffle (substantially) and the contest (somewhat)
      increased the amount of paper brought to a dorm's recycling center. Students
      whose rooms were closest to the collection center showed the greatest
      participation. Removal of the reinforcement contingencies resulted in a return to
      baseline levels.

PMID- 16795529
TI  - Correspondence between saying and doing: teaching children to share and praise.
AB  - Five small groups of preschool children were taught to share and praise by the
      modelling of these behaviors and reinforcement of their reports of sharing and
      praising. Experiment I demonstrated that modelling and reinforcement of any (true
      or untrue) reports of sharing, and then of praising, promptly increased reports
      of the corresponding behaviors. Modelling and reinforcement for true reports of
      each behavior increased both reporting and actual behavior. Experiment II showed
      that both reported and actual sharing and praising may be increased by modelling
      and reinforcement for true reports of the target behavior, without previous
      reinforcement for any (true or untrue) reports of those behaviors. Sharing, but
      not praising, generalized to a second setting. Experiment III replicated the
      results of Experiment II for sharing and praising, and demonstrated similar
      success in increasing a third behavior, specific praising. In general, these
      experiments show that developing correspondence between children's reports of
      behavior and actual behavior may be an efficient means of increasing prosocial
      responses.

PMID- 16795530
TI  - Shoplifting prevention: providing information through signs.
AB  - Shoplifting is one of the most frequent crimes in the United States, yet there is
      no agreement about effective prevention procedures. Since most prevention
      strategies are aimed at either increasing public awareness of the severity of the
      consequences or increasing the threat of detection, procedures that contain these
      elements were evaluated. Posting signs around a department of a department store
      pointing out that shoplifting is a crime, etc., partially reduced shoplifting
      rates. When merchandise that was frequently taken was identified by signs and
      stars, shoplifting decreased to near zero. Publicity campaigns to inform the
      public of consequences for shoplifting may produce desirable results, but
      identifying likely shoplifting targets, which may increase the likelihood of
      detection, effectively reduces shoplifting rates.

PMID- 16795531
TI  - The effects of instructions, incentive, and feedback on a community problem:
      dormitory noise.
AB  - A reinforcement system utilizing instructions, modelling, feedback, and group
      reinforcement was employed in an attempt to reduce disruptive noise on three
      university residence halls. A fourth hall received the same treatment program
      without the reinforcement component. Noise scores were determined by recording
      the number of discrete noise occurrences over a criterion decibel level. On all
      four residential floors, noise scores during treatment conditions were lower than
      initial and final baseline levels. Additionally, periods of noise reduction
      corresponded to the changing criterion multiple-baseline and reversal designs
      utilized. Pre- and posttreatment questionnaire responses from the three
      reinforcement floors paralleled changes in objective noise data. At
      posttreatment, residents reported less noise disturbance of study and sleep and
      more control over the noise situation and floor problems in general. These
      results indicated that a comprehensive behavior-modification treatment package
      was effective in reducing disruptive noise in university residence halls.
      Difficulties in data collection and anomalies in the data are discussed. Future
      directions for field-based behavior-modification research are outlined.

PMID- 16795532
TI  - The role of offer rates in controlling sharing by young children.
AB  - The effects of different reinforcement contingencies on the rates of offers to
      share and their corresponding rates of acceptance by two small groups of
      preschool children were investigated in two experiments. In the first experiment,
      food and praise were given after a 5-min play period to any subject who had made
      one or more offers to share during the play period. This procedure increased the
      rate of share-offers by all subjects. However, as share-offers increased, the
      percentage of offers accepted decreased. In the second experiment, reinforcement
      was made contingent on a subject reducing offers to share to only one or two per
      5-min period. This led to a higher percentage of the offers being accepted. The
      results suggest that by controlling the rate of a social behavior, the manner in
      which other persons in the environment respond to the behavior may also be
      influenced.

PMID- 16795533
TI  - A comparison of frequency, interval, and time-sampling methods of data
      collection.
AB  - Data representing high, medium, and low response rates in constant and
      nonconstant patterns were generated by electromechanical equipment to determine
      whether the same data collected by time-sampling, interval recording, and
      frequency recording would be represented similarly by each method. Results
      indicated: (1) that time-sampling provided an extremely inaccurate estimate of
      responding, and (2) that interval recording accurately represented responding of
      low and medium rates, but grossly underestimated high-rate responding.

PMID- 16795534
TI  - Self-reinforcement.
AB  - Self-reinforcement in operant situations generally refers to those arrangements
      in which the subject delivers to himself a consequence, contingent on his
      behavior. However, it is noted that the definition of all other types of
      reinforcement make its delivery contingent on the subject's behavior. What is
      actually at issue is the agent who defines whether or not the response required
      for reinforcement has been met. In self-reinforcement, the subject himself
      defines this. In the laboratory, this requirement is machine-defined; in school
      examinations, it is teacher-defined; and in many clinical self-control
      situations, it is also independently defined. A reinforcement contingency
      presupposes such independence, absent in self-reinforcement. Implications for
      research and practice are discussed and alternative formulations are offered.

PMID- 16795535
TI  - Terminal terminology: a self-regulated response to Goldiamond.

PMID- 16795536
TI  - Some encouraging thoughts about self-reinforcement.

PMID- 16795537
TI  - Fables, armadyllics, and self-reinforcement.

PMID- 16795538
TI  - Considerations in the choice of interobserver reliability estimates.
AB  - Two types of interobserver reliability values may be needed in treatment studies
      in which observers constitute the primary data-acquisition system: trial
      reliability and the reliability of the composite unit or score which is
      subsequently analyzed, e.g., daily or weekly session totals. Two approaches to
      determining interobserver reliability are described: percentage agreement and
      "correlational" measures of reliability. The interpretation of these estimates,
      factors affecting their magnitude, and the advantages and limitations of each
      approach are presented.

PMID- 16795539
TI  - Reviewer's comment: just because it's reliable doesn't mean that you can use it.

PMID- 16795540
TI  - Evaluating interobserver reliability of interval data.
AB  - Previous recommendations to employ occurrence, nonoccurrence, and overall
      estimates of interobserver reliability for interval data are reviewed. A
      rationale for comparing obtained reliability to reliability that would result
      from a random-chance model is explained. Formulae and graphic functions are
      presented to allow for the determination of chance agreement for each of the
      three indices, given any obtained per cent of intervals in which a response is
      recorded to occur. All indices are interpretable throughout the range of possible
      obtained values for the per cent of intervals in which a response is recorded.
      The level of chance agreement simply changes with changing values. Statistical
      procedures that could be used to determine whether obtained reliability is
      significantly superior to chance reliability are reviewed. These procedures are
      rejected because they yield significance levels that are partly a function of
      sample sizes and because there are no general rules to govern acceptable
      significance levels depending on the sizes of samples employed.

PMID- 16795541
TI  - A probability-based formula for calculating interobserver agreement.
AB  - Estimates of observer agreement are necessary to assess the acceptability of
      interval data. A common method for assessing observer agreement, per cent
      agreement, includes several major weaknesses and varies as a function of the
      frequency of behavior recorded and the inclusion or exclusion of agreements on
      nonoccurrences. Also, agreements that might be expected to occur by chance are
      not taken into account. An alternative method for assessing observer agreement
      that determines the exact probability that the obtained number of agreements or
      better would have occurred by chance is presented and explained. Agreements on
      both occurrences and nonoccurrences of behavior are considered in the calculation
      of this probability.

PMID- 16795542
TI  - Observer agreement, credibility, and judgment: some considerations in presenting
      observer agreement data.
AB  - Graphical and statistical indices employed to represent observer agreement in
      interval recording are described as "judgmental aids", stimuli to which the
      researcher and scientific community must respond when viewing observer agreement
      data. The advantages and limitations of plotting calibrating observer agreement
      data and reporting conventional statistical aids are discussed in the context of
      their utility for researchers and research consumers of applied behavior
      analysis. It is argued that plotting calibrating observer data is a useful
      supplement to statistical aids for researchers but is of only limited utility for
      research consumers. Alternatives to conventional per cent agreement statistics
      for research consumers include reporting special agreement estimates (e.g., per
      cent occurrence agreement and nonoccurrence agreement) and correlational
      statistics (e.g., Kappa and Phi).

PMID- 16795543
TI  - Artifact, bias, and complexity of assessment: the ABCs of reliability.
AB  - Interobserver agreement (also referred to here as "reliability") is influenced by
      diverse sources of artifact, bias, and complexity of the assessment procedures.
      The literature on reliability assessment frequently has focused on the different
      methods of computing reliability and the circumstances under which these methods
      are appropriate. Yet, the credence accorded estimates of interobserver agreement,
      computed by any method, presupposes eliminating sources of bias that can
      spuriously affect agreement. The present paper reviews evidence pertaining to
      various sources of artifact and bias, as well as characteristics of assessment
      that influence interpretation of interobserver agreement. These include
      reactivity of reliability assessment, observer drift, complexity of response
      codes and behavioral observations, observer expectancies and feedback, and
      others. Recommendations are provided for eliminating or minimizing the influence
      of these factors from interobserver agreement.

PMID- 16795544
TI  - Time-series analysis in operant research.
AB  - A time-series method is presented, nontechnically, for analysis of data generated
      in individual-subject operant studies, and is recommended as a supplement to
      visual analysis of behavior change in reversal or multiple-baseline experiments.
      The method can be used to identify three kinds of statistically significant
      behavior change: (a) changes in score levels from one experimental phase to
      another, (b) reliable upward or downward trends in scores, and (c) changes in
      trends between phases. The detection of, and reliance on, serial dependency
      (autocorrelation among temporally adjacent scores) in individual-subject
      behavioral scores is emphasized. Examples of published data from the operant
      literature are used to illustrate the time-series method.

PMID- 16795545
TI  - "Perhaps it would be better not to know everything.".
AB  - The advent of statistical methods for evaluating the data of individual-subject
      designs invites a comparison of the usual research tactics of the group-design
      paradigm and the individual-subject-design paradigm. That comparison can hinge on
      the concept of assigning probabilities of Type 1 and Type 2 errors. Individual
      subject designs are usually interpreted with implicit, very low probabilities of
      Type 1 errors, and correspondingly high probabilities of Type 1 errors, and
      correspondingly high probabilities of Type 2 errors. Group designs are usually
      interpreted with explicit, moderately low probabilities of Type 1 errors, and
      therefore with not such high probabilities of Type 2 errors as in the other
      paradigm. This difference may seem to be a minor one, considered in terms of
      centiles on a probability scale. However, when it is interpreted in terms of the
      substantive kinds of results likely to be produced by each paradigm, it appears
      that the individual-subject-design paradigm is more likely to contribute to the
      development of a technology of behavior, and it is suggested that this
      orientation should not be abandoned.

PMID- 16795546
TI  - Patrol evaluation research: a multiple-baseline analysis of saturation police
      patrolling during day and night hours.
AB  - The effects of a carefully monitored and increased police patrol on the report of
      crime were examined in four patrol zones. Overall patrol movement was increased
      to four times normal levels and slow patrol movement (under 20 mph) to around 30
      times normal levels for 10 days. The patrol was active in two zones between 9:00
      a.m. and 5:00 p.m. and in the other two zones between 7:00 p.m. and 3:00 a.m. A
      multiple-baseline design and time-series statistical analyses showed
      statistically reliable changes in reported levels of Part I crime (such as
      robbery, burglary, and aggravated assault) during both night patrols, but not in
      the day patrols. In both night-patrol zones, there were also reliable increases
      from saturation patrol to postsaturation patrol in report of Part I crime after
      the night patrol was terminated. Neither of the day patrols showed significant
      crime report changes on termination. Despite statistically reliable decreases in
      report of crime during nighttime hours, the value of saturation patrolling as a
      crime-prevention technique was questioned on cost/benefit grounds.

PMID- 16795547
TI  - Modification of school attendance for an elementary population.
AB  - The staff and students of a school composed of Grades 1 through 3 participated in
      a program to increase school attendance. Children earned the opportunity to
      attend part or all of a monthly party by their attendance. Immediate feedback
      occurred each morning by placing stars on a classroom chart for each child
      present. The school's attendance during the program was compared both with
      attendance during preceding years and with attendance at other schools. The
      experimental school's attendance improved dramatically to become the best of all
      elementary schools in the system.

PMID- 16795548
TI  - Gasoline conservation: a procedure for measuring and reducing the driving of
      college students.
AB  - The study sought to motivate college students to reduce the number of miles they
      drove each day and thus save gasoline. Students in two psychology classes were
      divided by class into two groups. The experimental group was offered various
      combinations of prizes such as cash, a tour of a mental-health facility, car
      servicing, and a university parking sticker for reducing driving. The value of
      the prize received was scaled in terms of per cent reduction in driving. The
      contrast group received no inducements. The condition in which the experimental
      group's mileage reduction was reinforced was counterbalanced by two baseline
      conditions. Several special recording procedures were used to reduce and detect
      the possibility of subjects altering their odometers, the source of the driving
      data. Experimental subjects reduced their average daily mileage by 20% relative
      to the initial baseline; the contrast group did not change. During the one-month
      reinforcement condition, the 12 experimental subjects saved some 170 gallons
      (worth $102) of gasoline.

PMID- 16795549
TI  - A review of the observational data-collection and reliability procedures reported
      in The Journal of Applied Behavior Analysis.
AB  - The research published in the Journal of Applied Behavior Analysis (1968 to 1975)
      was surveyed for three basic elements: data-collection methods, reliability
      procedures, and reliability scores. Three-quarters of the studies reported
      observational data. Most of these studies' observational methods were variations
      of event recording, trial scoring, interval recording, or time-sample recording.
      Almost all studies reported assessment of observer reliability, usually total or
      point-by-point percentage agreement scores. About half the agreement scores were
      consistently above 90%. Less than one-quarter of the studies reported that
      reliability was assessed at least once per condition.

PMID- 16795550
TI  - Effects of a token reinforcement system on journal reshelving.
AB  - A token reinforcement program involving two levels of token value and backup
      reinforcers to increase journal reshelving behavior in a large university library
      was experimentally evaluated. Results showed that instructions (in which signs
      asked users to reshelve journals) had no impact. By contrast, token reinforcement
      contingent on reshelving behavior led to a marked increase in journals reshelved.
      A return to instructions-only conditions, when data were corrected for library
      usage, showed an increase in unreshelved journals over the token reinforcement
      period, though the increase was not to baseline levels. For the next 11 months,
      library staff maintained a modified token program. Follow-up data collected after
      that interval showed that number of unreshelved journals remained markedly lower
      than levels at baseline and the first instructions-only period, though they were
      slightly higher than at the token reinforcement period. Token reinforcement of
      the variety employed in this study constitutes an efficient, economical means of
      changing the behavior of library users who fail to reshelve books and journals.

PMID- 16795551
TI  - The training and validation of youth-preferred social behaviors of child-care
      personnel.
AB  - This research sought to identify, train, and validate social behaviors preferred
      by youths to be used by youth-care personnel (called teaching-parents). With
      training, consistent increases in seven preferred behaviors were observed for the
      six teaching-parent trainees. These behaviors included offering to help, "getting
      to the point", giving reasons why a behavior is important to a youth, providing
      descriptions of alternative behaviors, positive feedback, smiling, and positive
      motivational incentives (i.e., points for task mastery exchanged for tangible
      reinforcers). Increases in these behaviors correlated with increases in the
      youths' ratings of the quality of the trainees' interactions. Posttraining levels
      of preferred social behavior and youth ratings for trainees also compared
      favorably with levels for successful professional teaching-parents. These results
      suggest that teaching-parents can be successfully trained to interact with youths
      in ways that are preferred by the youths.

PMID- 16795552
TI  - Peer tutoring among elementary students: educational benefits to the tutor.
AB  - To determine whether tutoring might be academically beneficial to the tutor, this
      study investigated the acquisition of spelling words by three elementary students
      in a peer tutoring program. The experimental design allowed a simultaneous
      comparison of each child's gain in performance on comparable word lists on which
      the child tutored another child, was tutored by another child, or neither gave
      nor received tutoring. The children's spelling improved nearly an equivalent
      amount on those words on which they tutored another child as on the words on
      which they were tutored; no such change was noted on the words on which they
      neither gave nor received tutoring. These findings, that peer tutoring is
      profitable for the tutor as well as the tutee, provide a basis for recommending
      peer tutoring as one method of individualizing education.

PMID- 16795553
TI  - Pyramid training of elementary school teachers to use a classroom management
      "skill package".
AB  - Three regular elementary teachers were trained in the use of a classroom
      management "skill package". Subsequently, each of these three teachers (tier 1 of
      training) trained three more teachers to use the same skill package (tier 2 of
      training). Direct behavioral measures of student disruptiveness were taken in the
      three tier-1 classrooms and four tier-2 classrooms, and permanent product
      measures of student productivity in arithmetic were taken in the three tier-1
      classrooms. Results indicated that student disruptiveness decreased at least as
      much in the tier-2 classrooms as in the tier-1 classrooms. Data also indicated
      that serving as trainers benefited two of the tier-1 teachers who profited least
      from the original training by producing further reductions in disruptiveness in
      their respective classrooms. Productivity data suggested that use of the "skill
      package" increased classroom academic output, especially for those students below
      the median in productivity during baseline. The investigators' time investment in
      training a tier-2 teacher was one-fourth that of training a tier-1 teacher.

PMID- 16795554
TI  - Effects of peer social initiations on the behavior of withdrawn preschool
      children.
AB  - Social approach to peers was evaluated as an intervention for isolate
      preschoolers. During baseline, confederate peers made few social approaches to
      the target subjects. Confederates greatly increased their rate of social
      approaches during the first intervention, decreased social approaches during a
      second baseline, and increased social approaches again in a second intervention
      phase. Increases in confederate social initiations immediately increased the
      frequency of subjects' positive social behavior. Additionally, five of six
      subjects showed an increase in their own positive social initiations during
      intervention periods. The results suggest that: (a) peers may be programmed to
      increase the positive social behaviors of their isolate classmates, and (b)
      remediating social deficits requires assessment and intervention specifically
      tailored to the individual child.

PMID- 16795555
TI  - Observer reliability as a function of circumstances of assessment.
AB  - THREE FACTORS CHARACTERISTIC OF EXPERIMENTAL SETTINGS WERE HYPOTHESIZED TO
      INFLATE ARTIFACTUALLY THE RELIABILITY OF OBSERVATIONAL RECORDINGS: (a) knowledge
      by observers of when and by whom their reliability is being assessed, (b) the
      absence of the experimenter or a monitor to prevent cheating, and (c) computation
      of reliability within- (versus between-) observer group. Three groups of four
      observers used a standard nine-category observational code for disruptive
      behavior in recording from videotapes of a classroom for 22 days. Analyses
      revealed considerable increases in average occurrence reliability as a function
      of the main effects of each of the experimental factors. The specific increases
      in reliability associated with each of the 12 combinations of the experimental
      factors are presented for each category of behavior. The possible role of
      observer-training procedures and behavioral definitions as determiners of
      nonartifactual reliability is discussed.

PMID- 16795557
TI  - Correspondence training, prior verbal training, and control of nonverbal behavior
      via control of verbal behavior.
AB  - The role of prior verbal training in correspondence training and later verbal
      control of nonverbal behavior was examined in two groups of Head Start children.
      One group received correspondence training without prior verbal training, the
      other with. Essentially no differences were found between the two sequences; thus
      it seems appropriate to consider the content phases (reinforcement contingent on
      target verbalization alone) of previous research as control procedures and not a
      necessary precursor to correspondence training.

PMID- 16795556
TI  - Taking a closer look: time sampling and measurement error.
AB  - A person manufactured his in-seat behavior for 15, 30-min sessions so that there
      were three blocks of five sessions where the behavior occurred 20%, 50%, and 80%
      of the time. Whole interval, partial interval, and momentary time-sample measures
      of the behavior were taken and compared to the continuous measure of the behavior
      i.e., per cent of time the behavior occurred. For interval time sampling, the
      difference between the continuous and sample measures i.e., measurement error,
      was: (1) extensive, (2) unidirectional, (3) a function of the time per response,
      and (4) inconsistent across changes in the continuous measure. A procedural
      analysis demonstrated that the frequency and duration of behavior are confounded
      in interval time sampling. Momentary time sampling was found to be superior to
      interval time sampling in estimating the duration a behavior occurs.

PMID- 16795558
TI  - A durable recording and feedback system.
AB  - A durable low-cost data-recording and feedback system is described. Data
      transcribed with a special pen onto a plastic sheet can be removed only with two
      solvents. These data can be displayed for feedback purposes without fear of
      destruction.

PMID- 16795559
TI  - Assessing the readability of thirty-nine behavior-modification training manuals
      and primers.
AB  - Thirty-nine behavior-modification training manuals and primers, sampling various
      topical areas, were subjected to a readability analysis. Reading-ease scores were
      computed by the formula developed by Flesch. The texts sampled ranged from very
      difficult (appropriate for college graduates) to fairly easy (appropriate for
      readers at the seventh-grade level).

PMID- 16795560
TI  - The use of teachers as behavioral observers.
AB  - The effect of using teachers as behavioral observers on both student and teacher
      behavior was examined with eight teachers and 32 elementary school children. The
      frequency of prompts (but not praise or criticism) to those students observed by
      the teacher increased significantly from nonobserver to teacher observed
      experimental phases. In addition, students observed by the teacher showed more
      change in appropriate behavior than students who were not observed. The
      significance of these findings for research and therapy is discussed.

PMID- 16795562
TI  - Evaluating municipal policy: an analysis of a refuse packaging program.
AB  - The effect of a municipal enforcement program to improve residents' packaging of
      refuse was analyzed in a multiple-baseline design across two areas of a city. The
      enforcement program involved instruction concerning refuse-packaging regulations,
      collection only of appropriately packaged refuse, and feedback notices to
      residents concerning the reasons for noncollection of their inadequately packaged
      refuse. Both the number of violations and the percentage of residences violating
      each day were markedly reduced during the enforcement program. Furthermore,
      sanitation workers considered that the packaging of refuse and the safety and
      efficiency of refuse collection had improved. This study served as a pilot
      evaluation of a policy change in the city sanitation department, and was
      functional in determining the direction of that policy.

PMID- 16795561
TI  - An implicit technology of generalization.
AB  - Traditionally, discrimination has been understood as an active process, and a
      technology of its procedures has been developed and practiced extensively.
      Generalization, by contrast, has been considered the natural result of failing to
      practice a discrimination technology adequately, and thus has remained a passive
      concept almost devoid of a technology. But, generalization is equally deserving
      of an active conceptualization and technology. This review summarizes the
      structure of the generalization literature and its implicit embryonic technology,
      categorizing studies designed to assess or program generalization according to
      nine general headings: Train and Hope; Sequential Modification; Introduce to
      Natural Maintaining Contingencies; Train Sufficient Exemplars; Train Loosely; Use
      Indiscriminable Contingencies; Program Common Stimuli; Mediate Generalization;
      and Train "To Generalize".

PMID- 16795563
TI  - Reducing residential electrical energy use: payments, information, and feedback.
AB  - Monetary payments, energy information, and daily feedback on consumption were
      employed to reduce electricity use in four units of a university student housing
      complex. A combined multiple-baseline and withdrawal design permitted both within
      and between-unit comparisons. Payments produced immediate and substantial
      reductions in consumption in all units, even when the magnitude of the payments
      was reduced considerably. Feedback also produced reductions, but information
      about ways to conserve and about the cost of using various appliances did not. It
      was also found that, in general, payments combined with either information or
      feedback produced no greater effect than payments alone.

PMID- 16795564
TI  - A multi-element analysis of the effect of teacher aides in an "open"-style
      classroom.
AB  - Open classrooms with few rules, individualized instruction, and informal class
      organization present new problems for the application of behavior principles. The
      effects of three types of teacher aides on student achievement and on-task
      behavior were studied. Each was compared with a standard no-aide condition.
      Subjects were 54 third graders in two "open"-style classrooms. The three types of
      aide, helping adult, disciplinary adult, and helping fifth-grade aide, were
      compared in a multi-element design with a no-aide control. The helping-adult aide
      significantly affected the academic output of the class, when compared with the
      no-aide condition. All aide conditions produced more academic work and on-task
      behavior than did the standard no-aide condition.

PMID- 16795565
TI  - An analysis of daily report cards and parent-managed privileges in the
      improvement of adolescents' classroom performance.
AB  - A daily report-card system, involving home privileges administered by parents,
      was developed for use with "problem" junior-high students. In Experiment I, when
      home privileges and parent praise were contingent on improved school conduct,
      classwork, daily grades, and teacher satisfaction, the school performance of
      three students improved considerably. In Experiment II, a similar report-card
      system was employed with two additional students, except only parent praise was
      contingent on improved school performance. Under these conditions, one of the
      students did not bring the report card home, and class performance did not
      improve until contingent home privileges were added. The school performance of
      the second student improved with the card and praise alone. However, there
      appeared to be a slow decline of classwork performance over time. For Experiment
      III, an instructional manual, describing the report-card program, was written for
      school guidance counsellors. Two guidance counsellors read the program, used it
      with one student each, and found that the school performance of both students
      improved. These results suggest that the daily report-card program with home
      consequences administered by parents can improve the school performance of, and
      teacher satisfaction about, students having considerable difficulty in school.

PMID- 16795566
TI  - Altering student responses through changes in teacher verbal behavior.
AB  - Two experiments were conducted in a junior-high special-education class of eight
      pupils in an inner-city school. In the first experiment, the teacher doubled the
      number of words used by the pupils in answering questions by altering the type of
      questions asked. In the second experiment, the number of words used by students
      and the percentage of answers given in complete sentences, increased from less
      than 5% to approximately 90% when the teacher instructed the pupils to answer in
      complete sentences and asked another pupil to answer using a sentence if the
      first one did not do so. In both experiments, a brief return to baseline
      conditions brought a return to low levels of verbal responding. An analysis of
      which pupils were called on by the teacher, teacher praise, and in the second
      experiment the types of questions asked, indicated that these variables were not
      responsible for the increases in verbal responding.

PMID- 16795567
TI  - Students' self-recording of manuscript letter strokes.
AB  - A method to allow students to self-record manuscript letter strokes was applied
      to three groups of first-grade school children. These children learned to use
      plastic overlays in some 80 to 120 min, with agreement between students and
      experimenter concerning correctness averaging 79%, 82%, and 84% in the three
      groups. A practical method allowing children to record their letter writing, thus
      receiving immediate feedback appears to have been demonstrated.

PMID- 16795568
TI  - Self-control techniques of famous novelists.
AB  - A statement by a famous contemporary novelist is presented that indicates how he
      and others, independently of formal behaviorism, used behavioristic methods
      specifically, self-recording charts and regularly scheduled daily work hours-to
      accelerate and maintain their writing outputs. On the basis of his statement and
      an analysis of his self-recorded data, it is argued that a meaningful and useful
      analogy can be drawn between writing a novel and emitting a simple operant
      response on a fixed-ratio schedule.

PMID- 16795569
TI  - Literary behavior analysis.

PMID- 16795570
TI  - A parent advice package for family shopping trips: development and evaluation.
AB  - THIS ARTICLE REPORTS ON THE PRIMARY STEPS IN THE DEVELOPMENT OF PARENT ADVICE FOR
      POPULAR DISSEMINATION: (a) developing advice for one specific problem situation,
      family shopping trips; (b) testing the advice program for benefit to children and
      convenience to adults; and (c) packaging the advice so it can be used
      successfully by interested parents. Systematic observation of 12 families using
      the written advice package on shopping trips revealed its effectiveness in
      reducing child disruptions and increasing positive interactions between parents
      and children. These findings, along with interview information from families,
      showed that the package is usable, effective, and popular with both parents and
      children, and thus is ready for dissemination to a wide audience of parents-a
      step that in itself should involve research and evaluation.

PMID- 16795571
TI  - A behavioral approach to coaching football: improving the play execution of the
      offensive backfield on a youth football team.
AB  - Because of the emphasis on winning, the difficulties involved in assessing
      performance, and the lack of frequent and contingent reinforcement, a behavioral
      approach to coaching football was used. The players, all nine- or ten-year-old
      males, were members of an offensive backfield on a Pop Warner football team.
      Three frequently-run offensive plays were broken down into a series of five
      behaviorally defined stages, permitting construction of checklists suitable for
      observing the players during both game and scrimmage sessions. The intervention
      consisted of the presentation and explanation of the appropriate checklist, and
      frequent contingent reinforcement in the form of feedback and recognition for
      instances of desired play execution. Performance gains averaging 20% occurred for
      each of the three plays after, and not before, the staggered introduction of each
      intervention. The results suggest that behavioral specification and positive
      reinforcement of desired play execution is a viable approach to the coaching of
      football.

PMID- 16795572
TI  - An experimental analysis of electricity conservation procedures.
AB  - Daily electricity consumption of four families was recorded for 106 days. A
      reversal design, consisting of various experimental conditions interspersed
      between repeated baseline conditions, was used. During experimental conditions,
      daily prompts (written conservation slogans attached to front doors) and/or daily
      feedback (daily kilowatts consumed and daily cost information) were in effect.
      Maximum consumption occurred during the initial baseline; minimum consumption
      occurred during different experimental conditions for different families. The
      mean decrease from the maximum to the minimum for all families was 35%. Reversals
      in consumption were demonstrated in three families, although successive baselines
      tended to decrease. No clear differences in effectiveness between prompting and
      feedback conditions were apparent. The procedures used resulted in considerable
      dollar savings for the families.

PMID- 16795573
TI  - Differential effects of fixed- and variable-time feedback on production rates of
      elementary school children.
AB  - The performance of 26 third-grade students who worked on individual weekly
      academic tasks was compared under fixed- and variable-time "home reports". During
      fixed-time home reports, each student was given a report to take home on Friday
      that indicated the quantity of work the student had completed that week,
      contained comments concerning the quality of the work, and had a space for
      parental remarks and signature. The same report was given during the variable
      time reports, except that seven to nine students were randomly selected each day
      to receive a home report. During variable-time reporting, students completed more
      assignments and completed assignments on a greater percentage of available
      workdays than during fixed-time reporting. The teachers' preference for the
      variable-time reporting was one additional advantage for the variable system.

PMID- 16795574
TI  - Community applications of instructional technology: teaching writers of
      instructional packages.
AB  - A community education program, to develop a variety of performance competencies
      in large numbers of neighborhood residents, requires a technology for preparing
      learning units administerable by community members themselves. The effects of a
      writing manual, designed to teach nonprofessionals to prepare such instructional
      packages, were analyzed in two experiments. Experiment I employed a multiple
      baseline design across three university student trainees. The results showed that
      appropriate program writing increased by 75% after completion of the manual. The
      results of Experiment II, with two low-income neighborhood residents serving as
      trainees, showed that packages produced by trained writers resulted in a greater
      increase in skill activities than sets of training stimuli produced by untrained
      writers.

PMID- 16795575
TI  - Community applications of instructional technology: training low-income proctors.
AB  - A community education system might be most effectively implemented in low-income
      communities if it were deliverable by neighborhood residents. A proctor training
      manual, designed to teach neighborhood residents how to administer standardized
      learning units to their peers, was analyzed in two experiments. The results of
      Experiment I showed that the percentage of occurrence of proctor behaviors
      increased after completion of the manual. Supplementary data suggest that
      specified proctor behaviors generalize to actual instructional situations. The
      results of Experiment II showed that the percentage of occurrence of trainee
      behaviors was higher when instructional packages were administered by trained
      proctors than when administered by untrained proctors. This study demonstrates an
      effective procedure for training low-income community residents to serve as
      proctors for a community education system.

PMID- 16795577
TI  - The behavioral junkie.

PMID- 16795576
TI  - The analysis of group contingency data.
AB  - The data analyses utilized in group contingency projects are reviewed. Previous
      studies are cited to emphasize advantages of nonconsolidated ("individual") over
      consolidated analyses. Several procedures are described that enable applied
      researchers to incorporate nonconsolidated data analyses in group contingency
      studies.

PMID- 16795578
TI  - Police evaluation research: an experimental and cost-benefit analysis of a
      helicopter patrol in a high crime area.
AB  - The significance of a helicopter patrol procedure directed toward prevention of
      home burglaries was evaluated from experimental and cost-benefit perspectives.
      The helicopter patrolled one city zone from 9 a.m. to 5 p.m. for two 12-day
      periods. Each 12-day period was separated by a baseline period in which only
      normal patrol-car levels were maintained. Significantly reduced burglary levels
      during the intervention periods, compared to baseline periods, documented the
      experimental significance of the helicopter procedure. The cash costs of
      implementing the patrol procedure were compared to two estimates of the resulting
      cash benefits. This latter cost-benefit analysis was supplemented by a discussion
      of the intangible costs and benefits of the helicopter procedure. Taken together,
      these analyses documented that the marginal costs of the helicopter intervention
      were exceeded by all estimates of benefits.

PMID- 16795579
TI  - The use and evaluation of study guides with middle school students.
AB  - Two experiments were conducted with 24 fifth-grade students participating. In the
      first experiment, quiz performance with study guides was compared to quiz
      performance without study guides. The group whose students received study guides
      always scored higher than the group who did not receive study guides. Experiment
      II assessed the feasibility of students scoring their own study guides. The
      reliability of student scoring was found to be 93% over all study guides and
      there were no significant differences between "self-scored" and "teacher-scored"
      groups on the weekly quizzes.

PMID- 16795581
TI  - Toward a solution: a rejoinder.

PMID- 16795580
TI  - The professional as a double-agent.

PMID- 16795583
TI  - Increasing the rate of presentation and use of signals in elementary classroom
      teachers.
AB  - Two issues relevant to competency-based teacher training were investigated-the
      specification of acceptable implementation levels for validated techniques and
      the necessity and feasibility of providing training on those techniques. First, a
      descriptive study was conducted to collect data on two direct-instruction
      teaching techniques-rate of presentation and signalling-that have been
      demonstrated to be functionally related to child performance in earlier studies.
      Data collected on 13 teachers, who received intensive preservice and inservice
      training, were then used as a standard for comparison in a multiple-baseline
      design across three untrained teachers to evaluate the effects of training on the
      two techniques. The experimental study served to determine whether training on
      the two techniques was necessary; and, if training was necessary, whether a
      training package, including supervised practice, unsupervised practice, and self
      critique, would result in adequate implementation levels for the two techniques.
      Low implementation levels during baseline for three untrained teachers indicated
      that training was necessary. With training, all teachers increased their levels
      of appropriately signalling pupil responses and accelerated their rates of
      presentation well above the levels of the comparison standard. Observations made
      one week and again four weeks after training ended showed that performance levels
      achieved during training were maintained.

PMID- 16795582
TI  - Multiple-probe technique: a variation on the multiple baseline.
AB  - Multiple-baseline and probe procedures are combined into a "multiple-probe"
      technique. The technique is designed to provide a thorough analysis of the
      relationship between an independent variable and the acquisition of a successive
      approximation or chain sequence. It provides answers to the following questions:
      (1) What is the initial level of performance on each step in the training
      sequence? (2) What happens if sequential opportunities to perform each next step
      in the sequence are provided before training on that step? (3) What happens when
      training is applied? (4) What happens to the performance of remaining steps in
      the sequence as criterion is reached in the course of training each prior step?
      The technique features: (1) one initial probe of each step in the training
      sequence, (2) an additional probe of every step after criterion is reached on any
      training step, and (3) a series of "true" baseline sessions conducted just before
      the introduction of the independent variable to each training step. Intermittent
      probes also provide an alternative to continuous baseline measurement, when such
      measurement during extended multiple baselines (1) may prove reactive, (2) is
      impractical, and/or (3) a strong a priori assumption of stability can be made.

PMID- 16795584
TI  - Effects of response cost on the behavior of a million persons: charging for
      directory assistance in Cincinnati.
AB  - An interrupted time-series analysis of local directory-assistance calls in the
      Cincinnati area from 1962 to 1976 revealed a significant reduction in the daily
      frequency of calls after charges were introduced in 1974. No reductions occurred
      in the daily frequency of long-distance directory-assistance calls, which
      remained free. The results attest to the efficacy of response-cost procedures
      with large subject populations in the natural environment. The applicability of
      response-cost procedures to social and business problems is discussed.

PMID- 16795585
TI  - Effects of serial versus concurrent task sequencing an acquisition, maintenance,
      and generalization.
AB  - Effects of serial and concurrent task presentation on skill acquisition,
      generalization, and maintenance were compared. Two severely retarded females
      participated. During serial training, items of one response class, tracing, were
      trained to mastery before those of a second task, vocal imitation. In the
      concurrent method, training on two different tasks, tracing and vocal imitation,
      alternated within sessions for fixed periods of time. There were no major
      differences between the serial and concurrent methods of instruction in the
      number of steps attained per behavior or in the number of trials required to
      reach criterion levels of performance. It was found however, that concurrent
      training resulted in more generalization. Retention results were not consistently
      related to training method.

PMID- 16795586
TI  - Increasing senior citizen participation in a community-based nutritious meal
      program.
AB  - Two experiments were conducted to compare the effects of several prompting and
      reinforcement procedures on the participation of elderly citizens in a nutritious
      meal program. Experiment I employed a variation of the multiple-baseline design
      across three groups of approximately 60 households each. Elderly persons not
      previously participating in the program were introduced to the following
      conditions: (1) public service radio announcements for four weeks to advertise
      the meal program and the availability of free transportation, (2) a home visit
      that served as a personal invitation and a second prompt for participation, (3) a
      followup telephone call, and (4) an incentive menu for participation, which was
      sent through the mail. Results indicated that the home visits and incentives were
      both effective as recruitment procedures and superior to other conditions;
      however, incentives proved to be the most cost-effective intervention. Experiment
      II used a variation of the multi-element design to compare the effects of
      scheduled activities and incentives in maintaining higher levels of participation
      by those persons who had attended the meal program at least once in the past, but
      whose current rate of participation was low. Results showed that activities
      improved attendance levels somewhat and that incentives substantially increased
      the number of meal program participants. Data from these experiments thus
      indicate that relatively inexpensive procedures may be used effectively to
      increase the extent to which elderly persons make use of potentially beneficial
      community-based services.

PMID- 16795587
TI  - Effects of intermittent modelling on observational learning.
AB  - A large research literature suggests that modelling in the absence of
      reinforcement for either the model's or the observer's behavior is a potent
      source of social learning. This literature is based entirely, however, on
      experiments using models that always display the critical behaviors. It is
      possible, therefore, that results obtained in these experiments would not
      generalize to natural settings in which modelling is intermittent. The effects of
      intermittent modelling were examined using three groups of 15 four- and five-year
      old children. Male and female children from middle-income families were
      individually exposed to an adult model who alternated descriptions of pictures of
      common objects. With one group, the model used no descriptive adjectives (color
      or number) in her descriptions after baseline; she used descriptive adjectives
      with 50% of the pictures with a second group, and 100% of the pictures with a
      third. Analyses of the data showed that the children substantially increased
      their use of descriptive adjectives in both modelling groups, but not in the no
      modelling group. The fact that there were no significant differences between the
      50% and 100% modelling groups suggests that results obtained in studies using
      consistent modelling can be generalized to natural settings.

PMID- 16795588
TI  - Natural rates of teacher approval and disapproval in grade-7 classrooms.
AB  - The natural rates of teacher verbal approval and disapproval in ten grade-seven
      classrooms were determined and compared with those described by White (1975).
      Although there were differences in the observation techniques used and the
      behavioral, cultural, and ethnic groups sampled, the results were similar. The
      majority of the teachers displayed individual rates of disapproval that were
      higher than their individual approval rates. The correlations between levels of
      on-task behavior and approval and disapproval rates were low. The issues raised
      by these findings are discussed in terms of directions for further research.

PMID- 16795590
TI  - Social validity: the case for subjective measurement or how applied behavior
      analysis is finding its heart.

PMID- 16795589
TI  - Generalization of parent-training results.
AB  - Two experiments were conducted to assess the generalized effects of several
      different parent/teacher training programs. In Experiment I it was found that a
      brief demonstration of how to teach an autistic child new behaviors was
      sufficient to teach parents how to teach those children those behaviors. However,
      generalization to new child-target behaviors did not take place. Another parent
      training program, which did not demonstrate how to teach any one specific child
      behavior, but was based on teaching the use of general behavior-modification
      procedures, was effective in teaching the parents how to teach new child-target
      behaviors. Experiment II then provided analyses of the individual effects of
      several components of the generalized training program. The results showed that
      videotape illustrations of the procedures, without the presence of a master
      teacher, were sufficient to teach the adults. However, sub-parts of the
      videotapes produced highly specific training results, with each component
      changing corresponding areas of the adults' behaviors. Viewing of the entire
      package was necessary before the adults were able to improve the autistic
      children's behaviors. The study as a whole suggests the importance of obtaining
      multiple measures of the effects of parent and teacher training programs,
      including measures of acquisition and generalization of both adult and child
      behaviors.

PMID- 16795591
TI  - Some thoughts on correspondence between saying and doing.
AB  - Recent research on verbal-nonverbal correspondence is evaluated, and conceptual,
      methodological, and applied issues regarding correspondence are addressed.
      Directions for research concerning the correspondence training procedure and
      extended applications are suggested.

PMID- 16795592
TI  - Effects of serial dependency on the agreement between visual and statistical
      inference.
AB  - Comparisons between visual and time-series inferences from behavioral data show
      that serial dependency in scores is likely to disrupt agreement between the two
      methods of analysis. If researchers follow an earlier recommendation that time
      series analysis be used to supplement or confirm visual analysis, this study's
      findings suggest that the two methods will disagree most often when the data
      contain high levels of autocorrelation and when reliable behavorial changes are
      indicated by time-series analysis.

PMID- 16795593
TI  - Teaching pedestrian safety skills to young children: an analysis and one-year
      followup.
AB  - Twenty-four elementary school children in grades K-3 participated in a study to
      teach six street-crossing skills: (1) wait at curb, (2) look all ways, (3) watch
      vehicle distance, (4) walk, (5) continue to look, and (6) use crosswalk. The
      effects of an instructional package implemented on the street corner were
      evaluated using a multiple-baseline design across two groups of six children at
      each of two schools. Rapid acquisition of pedestrian skills was evident at both
      schools. Average skill levels improved from 44% during baseline to 97% after
      training at School A and from 21% to 86% at School B. Data taken at a second
      street at each school were used to assess setting generality of safety behaviors.
      A one-year followup of 14 children indicated that pedestrian safety skills either
      maintained at high levels or could be quickly recovered from intermediate levels
      after remedial training. This research represents a first step in the solution of
      just one of the many community problems involving safety-deficient settings.

PMID- 16795594
TI  - Public transportation training: in vivo versus classroom instruction.
AB  - This study evaluated a classroom program to teach public transportation usage
      (bus-riding skills) to retarded persons. Based on a task analysis of specific
      skills, five retarded male students were taught each of the components of
      locating, signalling, boarding and riding, and exiting a bus. These skills were
      taught sequentially, using training procedures consisting of role playing,
      manipulating the actions of a doll on a simulated model, and responding to
      questions about slide sequences. Before, during, and after training, subjects
      were tested on generalization probes in the classroom and in the natural
      environment. Results of a multiple-baseline design across subjects indicated that
      up to 12 months after termination of training, each subject exhibited appropriate
      bus-riding skills on actual city buses. Two other subjects were trained on each
      skill component in vivo, on city buses, in order to compare the relative
      effectiveness and efficiency of classroom versus in vivo training. Both of these
      subjects acquired appropriate bus-riding skills; however, the in vivo training
      procedure was both more time consuming and expensive than classroom training.
      These findings further demonstrate the effectiveness and practicality of properly
      designed classroom training procedures for teaching community survival skills to
      retarded persons.

PMID- 16795595
TI  - A probabilistic model of intensive designs.
AB  - Without internal validity, experimental data are uninterpretable. With intensive
      designs, most methods presented to quantify a design's internal validity have
      been subject to criticism. A probabilistic model of intensive designs is
      presented that demonstrates the high degree of internal validity of these designs
      without relying on adaptations from traditional inferential statistics. Where the
      experimenter is able to conform to the restrictions of the model, the equations
      provide an estimation of internal validity for either reversal or multiple
      baseline designs. More importantly, the model provides mathematical bases for
      some of the common recommendations and design considerations in intensive
      research (such as the desirability of within-subject replications and of four or
      more multiple baselines).

PMID- 16795596
TI  - Training generalized improvisation of tools by preschool children.
AB  - The development of new, "creative" behaviors was examined in a problem-solving
      context. One form of problem solving, improvisation, was defined as finding a
      substitute to replace the specifically designated, but currently unavailable,
      tool ordinarily used to solve the problem. The study examined whether preschool
      children spontaneously displayed generalized improvisation skills, and if not,
      whether they could be trained to do so within different classes of tools.
      Generalization across different tool classes was monitored but not specifically
      trained. Five preschool children participated in individual sessions that first
      probed their skill at improvising tools, and later trained and probed generalized
      improvisation in one or more of three tool classes (Hammers, Containers, and
      Shoelaces), using a multiple-baseline design. All five children were trained with
      Hammers, two were trained in two classes, and two were trained in all three tool
      classes. Four of the five children improvised little in Baseline. During
      Training, all five showed increased generalized improvisation within the trained
      class, but none across classes. Tools fabricated by item combinations were rare
      in Baseline, but common in Training. Followup probes showed that the training
      effects were durable.

PMID- 16795597
TI  - The effects of feedback and consequences on transitional cursive letter
      formation.
AB  - Twelve first-grade students were employed to analyze the effects of (1) Verbal
      and Visual Feedback, (2) Verbal and Visual Feedback plus immediate rewriting of
      trained letters with one or more incorrect letter strokes, and (3) Potential
      Reinforcement on cursive letter strokes. Students practised both a set of trained
      and a set of untrained letters during each session. Feedback and reinforcement
      was administered only for trained letter strokes. The percentage of correct
      trained letter strokes increased during all conditions. Performance on the
      untrained but practiced and trained letter strokes followed the same general
      trend in response pattern. No consistent pattern of generalization was
      demonstrated with untrained and unpracticed letter strokes.

PMID- 16795598
TI  - Finders, keepers?: an analysis and validation of a free-found-ad policy.
AB  - A SURVEY OF LOST AND FOUND CLASSIFIED SECTIONS IN METROPOLITAN AND SMALLER
      NEWSPAPERS REVEALED DISPARATE RATES BETWEEN LOST ADS AND FOUND ADS: Lost ads
      greatly outnumbered Found ads, probably because newspapers usually require the
      finders of lost personal property to pay for Found advertisements. The effect of
      a Free-Found-Ad policy on the rate of Found advertisements placed in the Lost and
      Found sections of three community newspapers was investigated using a multiple
      baseline design. The results suggested that the Free-Found-Ad policy was
      effective in increasing the rates of Found ads in all three newspapers. To
      determine whether increases in Found ads resulted in increases in recovered
      property, a sample of individuals who placed Found ads were surveyed in both
      baseline and treatment conditions and asked if the found items had been claimed
      by their owners. The Free-Found-Ad policy appeared to be effective in increasing
      the amount of personal property returned. The study concluded that community
      newspapers can provide incentives to increase such help-giving or altruistic
      behaviors. The implications of this study for a general policy-research strategy
      are discussed.

PMID- 16795599
TI  - The effect of witnessing consequences on the behavioral recordings of
      experimental observers.
AB  - The cueing effects of interviewer praise contingent on a target behavior and
      expectation of behavior change were examined with six observers. Experiment I
      investigated the effect of cues in conjunction with expectation. Experiment II
      assessed the relative contributions of cues and expectation, and Experiment III
      examined the effect of cues in the absence of expectation. The frequencies of two
      behaviors, client eye contact and face touching, were held constant throughout a
      series of videotaped interviews between an "interviewer" and a "client". A within
      subjects design was used in each experiment. During baseline conditions, praise
      did not follow eye contact by the client on the videotape. In all experimental
      conditions, praise statements from the interviewer followed each occurrence of
      eye contact with an equal number of praises delivered at random times when there
      was no eye contact. Three of the six observers dramatically increased their
      recordings of eye contact during the first experimental phase, but these
      increases were not replicated in a second praise condition. There were no
      systematic changes in recorded face touching. Witnessing the delivery of
      consequences, rather than expectation seemed to be responsible for the effect.
      This potential threat to the internal validity of studies using observational
      data may go undetected by interobserver agreement checks.

PMID- 16795600
TI  - A method for combining occurrence and nonoccurrence interobserver agreement
      scores.
AB  - Various statistics have been proposed as standard methods for calculating and
      reporting interobserver agreement scores. The advantages and disadvantages of
      each have been discussed in this journal recently but without resolution. A
      formula is presented that combines separate measures of occurrence and
      nonoccurrence percentages of agreement, with weight assigned to each measure,
      varying according to the observed rate of behavior. This formula, which is a
      modification of a formula proposed by Clement (1976), appears to reduce
      distortions due to "chance" agreement encountered with very high or low observed
      rates of behavior while maintaining the mathematical and conceptual simplicity of
      the conventional method for calculating occurrence and nonoccurrence agreement.

PMID- 16795601
TI  - A survey of parent training manuals.
AB  - Twenty-six commercially available parent training manuals were surveyed with the
      goal of providing helpful information to the professional for selection of
      manuals. Included were manuals for parents as well as manuals for professionals
      for use in conducting individual or group treatment. The following information
      was given for all manuals: the characteristics of the target populations for whom
      the manuals were intended, readability levels, use made of technical language,
      provision of glossary, organization and format of the book, availability of
      supplementary materials such as leaders' guides, and references to reviews by
      other authors. In an additional section, the research literature dealing with
      evaluation of these manuals was reviewed and summarized as a means of acquainting
      the reader with the available scientific information on their effectiveness. A
      report on the status of each manual in terms of evaluation was provided in
      tabular form. The evaluation of manuals by conduct of empirical research to
      determine their usefulness to the consumer was emphasized.

PMID- 16795602
TI  - Adjunctive behavior: an under-reported phenomenon in applied behavior analysis?

PMID- 16795603
TI  - Effects of self-monitoring and feedback on residential electricity consumption.
AB  - Prior research has indicated that frequent feedback could reduce residential
      electricity consumption by 10% to 15%. However, because feedback was primarily
      given in written form, this procedure might not be practical. The present study
      evaluated a potentially more practical feedback procedure during peak-use periods
      with high electricity consuming households. The study was conducted during the
      winter in an upper-middle class neighborhood of almost identical, all-electric
      townhouses (N = 71) that averaged about 170 KWH per day per household for a
      monthly bill of over $200. Twelve households received daily written feedback.
      Sixteen households (self-monitoring) were taught to read their outdoor
      electricity meter and to record KWH used every day. A comparison group was
      composed of 14 households that had volunteered to participate and 29 others that
      had only given permission to have their meters read. During a 1-month period that
      the procedures were in effect, the feedback group reduced consumption by 13% and
      the self-monitoring group by about 7%. These reductions, relative to the
      comparison group, were maintained during an early spring 1-month follow-up period
      and, to a lesser extent, during a 6-week warm spring period. Self-monitoring
      participants were highly reliable and persistent meter readers. Reductions in
      electricity use were reported by households to be largely attributable to
      lowering of the heat thermostat, and large monetary and KWH savings were found.
      Techniques to make self-monitoring cost-effective important components of the
      self-monitoring procedure, methods to apply self-monitoring more broadly, and
      plans to combine behavioral procedures with physical technology are discussed.

PMID- 16795604
TI  - Standardized classroom management program: Social validation and replication
      studies in Utah and Oregon.
AB  - A comprehensive validation study was conducted of the Program for Academic
      Survival Skills (PASS), a consultant-based, teacher-mediated program for student
      classroom behavior. The study addressed questions related to: (a) brief
      consultant training, (b) subsequent teacher training by consultants using PASS
      manuals, (c) contrasts between PASS experimental teachers and students and
      equivalent controls on measures of teacher management skills, student classroom
      behavior, teacher ratings of student problem behaviors, and academic achievement,
      (d) reported satisfaction of participants, and (e) replication of effects across
      two separate school sites. Results indicated that in both sites significant
      effects were noted in favor of the PASS experimental group for (a) teacher
      approval, (b) student appropriate classroom behavior, and (c) four categories of
      student inappropriate behavior. Program satisfaction ratings of students,
      teachers, and consultants were uniformly positive, and continued use of the
      program was reported a year later. Discussion focused upon issues of cost
      effectiveness, differential site effects, and the relationship between
      appropriate classroom behavior and academic achievement.

PMID- 16795605
TI  - Percentage agreement and phi: A conversion table.
AB  - STUDIES IN APPLIED BEHAVIOR ANALYSIS HAVE USED TWO EXPRESSIONS OF RELIABILITY FOR
      HUMAN OBSERVATIONS: percentage agreement (including percentage occurrence and
      percentage nonoccurrence agreement) and correlational techniques (including the
      phi coefficient). The formal relationship between these two expressions is
      demonstrated, and a table for converting percentage agreement to phi, or vice
      versa, is presented. It is suggested that both expressions be reported in order
      to communicate reliability unambiguously and to facilitate comparison of the
      reliabilities from different studies.

PMID- 16795606
TI  - Sharing in preschool children: Facilitation, stimulus generalization, response
      generalization, and maintenance.
AB  - Three approaches to facilitating verbal and physical sharing and of the
      generalizability and durability of the behaviors that were trained were
      investigated. During a free play period, groups of preschool children were taught
      to share verbally, to share physically, or to share verbally and physically;
      another group was not trained. Immediately following free play, the children were
      observed in a different setting. Follow-up was conducted 4 weeks after training
      ended. Physical sharing that was durable and generalizable resulted only when
      children were taught to share verbally. Increases in physical sharing produced by
      training children to share only physically were not durable and did not
      generalize. Training both verbal and physical sharing produced results with a
      magnitude slightly greater than teaching just verbal sharing. Despite a lack of
      special programming, some of the treatment effects generalized to another setting
      and were maintained during the Follow-up. There was response generalization of
      the effects of training verbal sharing to physical sharing but not vice versa.
      Problems with the concept of response class, a methodological suggestion for
      studying response generalization, and possibilities concerning why generalization
      and maintenance occurred without specific programming are discussed.

PMID- 16795608
TI  - Comparison of observational recordings in vivo, via mirror, and via television.
AB  - Simultaneous observational recordings were made in vivo, via an observation
      mirror, and via closed circuit television. Three of nine observers had extensive
      experience recording behavior in vivo; three had extensive experience recording
      behavior via mirror; and three had extensive experience recording via television.
      Observers recorded nine categories of disruptive behavior for children in a
      special class setting. Frequencies of behavior recorded in vivo, via mirror, and
      via television differed significantly for only one category, vocalization. There
      were no significant main effects or interactions involving the observers'
      previous experience. Occurrence reliability coefficients computed within and
      between media demonstrated the similarity of observer agreement in all three
      media. Data collection procedures using an observational mirror or closed circuit
      television appear to be reasonable alternatives to in vivo observation in
      circumstances similar to those in the present study.

PMID- 16795607
TI  - The nature of behavioral assessment: A commentary.
AB  - This special issue of the Journal of Applied Behavior Analysis provides the
      reader with a sample of current work in behavioral assessment. The purpose of
      this paper is to present an overview of behavioral assessment and to place the
      other articles in context of this developing area.

PMID- 16795609
TI  - A graphical judgmental aid which summarizes obtained and chance reliability data
      and helps assess the believability of experimental effects.
AB  - Interval by interval reliability has been criticized for "inflating" observer
      agreement when target behavior rates are very low or very high. Scored interval
      reliability and its converse, unscored interval reliability, however, vary as
      target behavior rates vary when observer disagreement rates are constant. These
      problems, along with the existence of "chance" values of each reliability which
      also vary as a function of response rate, may cause researchers and consumers
      difficulty in interpreting observer agreement measures. Because each of these
      reliabilities essentially compares observer disagreements to a different base, it
      is suggested that the disagreement rate itself be the first measure of agreement
      examined, and its magnitude relative to occurrence and to nonoccurrence
      agreements then be considered. This is easily done via a graphic presentation of
      the disagreement range as a bandwidth around reported rates of target behavior.
      Such a graphic presentation summarizes all the information collected during
      reliability assessments and permits visual determination of each of the three
      reliabilities. In addition, graphing the "chance" disagreement range around the
      bandwidth permits easy determination of whether or not true observer agreement
      has likely been demonstrated. Finally, the limits of the disagreement bandwidth
      help assess the believability of claimed experimental effects: those leaving no
      overlap between disagreement ranges are probably believable, others are not.

PMID- 16795610
TI  - Back to basics: Percentage agreement measures are adequate, but there are easier
      ways.
AB  - Percentage agreement measures of interobserver agreement or "reliability" have
      traditionally been used to summarize observer agreement from studies using
      interval recording, time-sampling, and trial-scoring data collection procedures.
      Recent articles disagree on whether to continue using these percentage agreement
      measures, and on which ones to use, and what to do about chance agreements if
      their use is continued. Much of the disagreement derives from the need to be
      reasonably certain we do not accept as evidence of true interobserver agreement
      those agreement levels which are substantially probable as a result of chance
      observer agreement. The various percentage agreement measures are shown to be
      adequate to this task, but easier ways are discussed. Tables are given to permit
      checking to see if obtained disagreements are unlikely due to chance.
      Particularly important is the discovery of a simple rule that, when met, makes
      the tables unnecessary. If reliability checks using 50 or more observation
      occasions produce 10% or fewer disagreements, for behavior rates from 10% through
      90%, the agreement achieved is quite improbably the result of chance agreement.

PMID- 16795611
TI  - Applied behavior analysis and interobserver reliability: A commentary on two
      articles by Birkimer and Brown.

PMID- 16795612
TI  - Just because it's reliable doesn't mean it's believable: A commentary on two
      articles by Birkimer and Brown.

PMID- 16795613
TI  - On the not so recent invention of interobserver reliability: A commentary on two
      articles by Birkimer and Brown.

PMID- 16795614
TI  - Proposed conventions for evaluating observer reliability: A commentary on two
      articles by Birkimer and Brown.

PMID- 16795615
TI  - Reliability in the context of the experiment: A commentary on two articles by
      Birkimer and Brown.
AB  - Two sources of variability must each be considered when examining change in level
      between two sets of data obtained by human observers; namely, variance within
      data sets (phases) and variability attributed to each data point (reliability).
      Birkimer and Brown (1979a, 1979b) have suggested that both chance levels and
      disagreement bands be considered in examining observer reliability and have made
      both methods more accessible to researchers. By clarifying and extending Birkimer
      and Brown's papers, a system is developed using observer agreement to determine
      the data point variability and thus to check the adequacy of obtained data within
      the experimental context.

PMID- 16795616
TI  - Why the "I've got a better agreement measure" literature continues to grow: A
      commentary on two articles by Birkimer and Brown.

PMID- 16795617
TI  - Inconsistent visual analyses of intrasubject data.
AB  - Visual inspection has been the method of analysis most widely employed to
      evaluate the functional control demonstrated by any given set of intrasubject
      replication data. To identify the influence of certain graphic characteristics on
      these evaluative behaviors, 36 "ABAB reversal" figures were constructed. They
      were sent to 250 reviewers of behavioral journals. Their evaluation of each
      figure was expressed as a rating on a 100-point scale of "experimental control."
      Mean interrater agreement was 0.61. In addition to this rating, a verbal
      description of evaluation criteria was requested. It was also found that graphic
      characteristics determine evaluative judgments in concert rather than singly. For
      example, phase mean changes had to be a pattern consistent with the hypothesized
      effect of the experimental variables, while degrees of mean shift and variability
      were less important. A description of the following evaluative criteria was
      presented: (a) topographic characteristics, (b) format of data presentation, (c)
      intra-experimental, and (d) extra-experimental circumstances.

PMID- 16795618
TI  - Issues in multivariate assessment of a large-scale behavioral program.
AB  - Several social and research issues directly affected the development and
      implementation of multivariate assessment in a large community-based applied
      research program. Examples are drawn from experiences of the Preparation through
      Responsive Educational Programs Project for disruptive and skill deficient
      adolescents in suburban, rural, and urban junior high school settings, focusing
      on the assessment of academic and social skill development and long-term skill
      maintenance. The social context altered both project treatment and follow-up
      plans, requiring assessment of potentially unintended effects and decreasing
      consistency across sites. Future community acceptance of such programs may depend
      on the investigators' adaptation to diverse community pressures for program
      conduct and assessment and the measurement of phenomena that are not always
      directly observable.

PMID- 16795619
TI  - Issues in the assessment of social competence in children.
AB  - Recent interest in children's social competence has been prompted by findings of
      correlational and retrospective studies that indicate a positive relationship
      between early social adjustment problems of children and their adjustment later
      in life. To date, the assessment methodology in the area has pursued two
      directions: (1) sociometric measures (peer nomination and peer rating scales),
      which have provided the major means of identifying the socially competent child,
      and (2) direct observation, principally employed in the specification of socially
      competent behaviors. The current uses and the inherent assets and limitations of
      both strategies are discussed along with suggestions for enhancing current data
      collection methods. Issues concerning the definition of social competence,
      generalizability of current findings, and social norms are also examined.

PMID- 16795620
TI  - The quantity and quality of marital interaction related to marital satisfaction:
      A behavioral analysis.
AB  - An assessment instrument is presented for the evaluation of the quantity and
      quality of dyadic interaction, as well as for the daily recording of behaviors
      presented and omitted which influence marital satisfaction. Comparison of data
      from ten happy couples and from ten couples entering therapy indicated two
      distinct dysfunctional patterns among distressed couples, with significantly
      different patterns of time-together and positive/negative ratios differentiating
      the happy versus therapy groups. Independent behavioral recording for 14
      consecutive days significantly increased husband-wife agreement on a traditional
      adjustment questionnaire without significantly increasing or decreasing the level
      of satisfaction being assessed. There was no difference between groups as to
      interspousal agreement on amount of time together. However, the happy couples
      agreed on daily quality ratings of the 72 15-minute segments significantly more
      often than did the distressed couples. Couples at the extremes of the happy
      distressed continuum reported rewarding and punishing, respectively, in response
      to the partners presence, regardless of behaviors emitted. Midrange happy couples
      defined "pleasant" as positive behaviors presented; midrange distressed couples
      defined "pleasant" as negative behaviors omitted. Theoretical and clinical
      implications of behavioral analysis of sequential patterns are discussed.

PMID- 16795621
TI  - Multivariate effects of demand characteristics on the analogue assessment of
      heterosocial competence.
AB  - The present study assessed the effects of a contextual demand manipulation
      (pretreatment assessment versus experiment) and an instructional demand
      manipulation (high demand for competent behavior versus neutral demand) on the
      analogue assessment of heterosocial competence. Also assessed was the interaction
      between each demand manipulation and subject characteristics (high-frequency
      dating/low heterosocially anxious versus low-frequency dating/high heterosocially
      anxious college males). Students were assigned randomly to one of four groups
      receiving differential information and instructions. Students completed a battery
      of five standard paper-and-pencil questionnaires, responded out loud to 10 taped
      social situations, and conversed with a female confederate while being videotaped
      for five minutes. Multivariate analyses revealed highly significant differences
      between subject groups and between contextual manipulation groups. Univariate
      analyses revealed that only 3 of the 16 dependent measures, including 2 of the
      self-reports, were significantly affected by the contextual demand. Results are
      discussed in light of previous studies of phobic behavior and social skills.
      Various avenues for future research were presented.

PMID- 16795622
TI  - Unobtrusive measures in behavioral assessment.
AB  - A major distinguishing characteristic of behavioral assessment is the direct
      assessment of overt behavior. Direct assessment is assumed to provide a sample of
      behavior that reflects client performance in the situation in which behavior is
      assessed, even if the assessment procedures were not implemented. Yet, in the
      majority of investigations, behavioral assessment procedures are obtrusive, i.e.,
      subjects are aware that their behavior is being assessed. The potential problem
      with obtrusive assessment is that it may be reactive, i.e., affect how subjects
      perform. Recent research has demonstrated that obtrusive observations often are
      reactive and that behaviors assessed under obtrusive and unobtrusive conditions
      bear little relation. From methodological and applied perspectives, additional
      attention needs to be given to unobtrusive measures of behavior change. The
      present paper illustrates unobtrusive measures in behavior modification including
      direct observations, archival records, and physical traces of performance. In
      addition, validation and assessment problems, questions about the obtrusiveness
      of the measures, and ethical issues are discussed.

PMID- 16795623
TI  - The applicability of a helicopter patrol procedure to diverse areas: A cost
      benefit evaluation.
AB  - The residential burglary deterrent effects of a helicopter patrol procedure were
      investigated in four separate areas with a multiple baseline technology. The
      helicopter was flown during an 8:00 a.m. to 4:00 p.m. period in two high density
      population areas of approximately 9.82 and 14.71 square miles and two low density
      population areas of 117.49 and 89.97 square miles. The helicopter patrol reduced
      residential burglaries without crime displacement in the two high density areas
      but had no deterrent effects in the low density areas. The costs of the
      helicopter patrol were justified by the benefits that resulted from the reduced
      home burglaries in the two high density areas. Because the helicopter patrol
      program is funded by general tax revenues, there is a disparity between those
      people paying for the procedure (all residents of Nashville) and those citizens
      that receive the burglary deterrent benefits (only residents of high-density
      areas). This distribution of benefit limitation suggests two courses of action:
      (1) The helicopter should be flown only in high population density areas even
      though the low population density areas are also victimized by high burglary
      rates. (2) A more comprehensive burglary reduction program must be developed so
      that effective deterrence can be realized in low density areas. These latter
      techniques would supplement helicopter patrol strategies and thus form a
      comprehensive burglary deterrent package that has an equitable benefit
      distribution.

PMID- 16795624
TI  - Consequence analysis: Its effects on verbal statements about an environmental
      project.
AB  - Typically, citizens lack relevant information concerning possible consequences of
      proposed environmental projects. Despite federal requirements for citizen
      participation in decisions about proposed roadway projects, no systematic
      procedures exist for educating citizens as to the possible consequences of such
      projects. The effects of a consequence analysis procedure on community residents'
      verbal statements about the favorability of a proposed roadway project were
      assessed. The consequence analysis procedure involved asking residents to rate
      the desirability and magnitude of each of 48 possible consequences of the
      proposed roadway project. Following the intervention, overall ratings of
      favorability of the project changed for nine of ten residents. Community
      residents' ratings of the quality of participants' justifications of their
      position on the roadway issue provided evidence of generalization to this
      collateral behavior.

PMID- 16795625
TI  - The technical drift of applied behavior analysis.
AB  - Four dimensions (applied, analytic, general, conceptual) were selected from Baer,
      Wolf, and Risley's (1968) seminal article on the nature of applied behavior
      analysis and were monitored throughout the first 10 volumes of the Journal of
      Applied Behavior Analysis. Each of the experimental articles in Volumes 1 through
      6 and the first half of Volumes 7 through 10 was rated on each of these
      dimensions. The trends showed that applied behavior analysis is becoming a more
      purely technical effort, with less interest in conceptual questions. We are using
      simpler experimental designs and are conducting fewer analogue studies. Although
      concern for maintenance is increasing, other forms of generality are being
      measured or analyzed less often. These trends are discussed in terms of a
      technical drift in applied behavior analysis.

PMID- 16795626
TI  - Behavioral coaching in the development of skills in football, gymnastics, and
      tennis.
AB  - A review of the literature indicates that methods of skill acquisition based on
      the operant paradigm have been scientifically validated with many motor
      behaviors. However, these procedures have been limited to the use of positive
      reinforcement for correct performance when applied to the acquisition of complex
      sports skills in natural settings. To find complementary procedures to enhance
      skill acquisition, a coaching method involving several behavioral techniques was
      developed that focused on remediation of errors. This coaching method combined
      the following components: (1) systematic use of verbal instructions and feedback,
      (2) positive and negative reinforcement, (3) positive practice, and (4) time out.
      Three sports, football, gymnastics, and tennis, were selected to determine the
      effectiveness and generality of this behavioral coaching method. A total of 23
      male and female subjects, ranging in age from 11 to 35, was included in this
      study. Baseline data were first collected for each sport under standard coaching
      conditions. Next, the behavioral coaching method was evaluated depending on the
      sport in either a multiple baseline or a reversal design. The behavioral
      dimensions selected were blocking in football; backward walkovers, front hand
      springs, and reverse kips in gymnastics; and the forehand, backhand, and serve in
      tennis. Behavioral coaching was immediately effective in increasing the correct
      execution of complex skills in all three sports. Gains of up to 10 times the
      baseline performance were achieved in each sport. In football, behavioral
      coaching resulted in an increase in correct blocking performance from a baseline
      average of 5% to 51.3%. Gymnasts' performances increased from baseline averages
      of 2.7% to 52.6% across the three skills. In tennis, standard coaching produced
      an average of 6% correct performance which increased dramatically under
      behavioral coaching to 57% across the three strokes. The success of the
      behavioral coaching package used here suggests that a technology of behavior may
      offer additional and complementary strategies to the acquisition of motor skills
      in the natural environment.

PMID- 16795628
TI  - Police and prosecution systems: An evaluation of a police criminal case
      preparation program.
AB  - Program evaluation can provide objective information relevant to decisions on
      program maintenance. A program to address problems in the preparation of criminal
      investigation reports in a metropolitan police department was evaluated. The
      program permanently altered environmental conditions under which reports were
      prepared to facilitate performance. Police officers, who had previously prepared
      reports without assistance, visited the Case Preparation Room to prepare reports
      with assistance from office personnel. Compared to reports prepared without
      assistance, reports prepared in the Case Preparation Room documented more case
      elements required by the state legal code for criminal prosecution, were
      completed in fewer days following arrests, and received higher ratings from
      Assistant District Attorneys. Operation of a permanent program available to
      approximately 945 officers proved a practical solution to improving the
      preparation of criminal investigation reports.

PMID- 16795627
TI  - An analysis of public posting in reducing speeding behavior on an urban highway.
AB  - The effects of public posting on speeding behavior on an urban highway were
      assessed using a reversal design. During baseline the percentage of drivers
      speeding was measured with a concealed radar unit. During the daily posting
      condition a highway sign was installed which provided feedback on the percentage
      of drivers not speeding yesterday and the best record to date. This sign was then
      covered and reintroduced. Results indicated that the sign was effective in
      reducing speeding behavior. Furthermore, the effects were most pronounced in
      reducing the speeds of the faster drivers. Next, daily and weekly postings were
      compared with the sign alone without numerical feedback: results revealed that
      the weekly posting condition was as effective as the daily posting condition, but
      that the sign had no influence when numbers were not posted. Finally, the weekly
      posting procedure remained effective during a 6-month follow-up condition.

PMID- 16795629
TI  - Methodological problems in the use of participant observers.
AB  - A multiple baseline design across observed students and teachers was used to
      investigate the relationship between observations by participant observers and
      changes in the behavior of those observed ("observee" reactivity) and the
      observers (observer-mediator reactivity). Two teachers recorded consecutively the
      appropriate student verbalizations of four students and two teachers recorded the
      inappropriate student verbalizations of four students. Independent observers
      simultaneously recorded student verbalizations (appropriate and inappropriate) as
      well as teacher behaviors (positive, negative, and instruction) throughout all
      phases of the study. The results substantiated the prediction of "observee"
      reactivity and observer-mediator reactivity in one of four classrooms. The
      results of the present study suggest that in some instances, observations by
      participant observers may result in changes in the behavior of those being
      observed ("observee" reactivity) and/or the observers (observer-mediator
      reactivity).

PMID- 16795630
TI  - Some promising dimensions for behavioral community technology.
AB  - In recent years, the search for effective and replicable approaches to planned
      change in communities has escalated. Applied behavior analysts have participated
      in these efforts to remedy existing community problems and to increase the
      capacities of community residents to meet their goals. Examples of behavioral
      technologies for community settings are described and their advantages are noted.
      Criteria for more contextually appropriate community technologies are suggested
      and strategies for developing behavioral methods according to these criteria are
      described. This paper outlines some promising dimensions for behavioral community
      technology and discusses several possible limitations to a behavioral approach to
      addressing societal problems.

PMID- 16795631
TI  - Observation procedure, observer gender, and behavior valence as determinants of
      sampling error in a behavior assessment analogue.
AB  - Several factors thought to influence the representativeness of behavioral
      assessment data were examined in an analogue study using a multifactorial design.
      Systematic and unsystematic methods of observing group behavior were investigated
      using 18 male and 18 female observers. Additionally, valence properties of the
      observed behaviors were inspected. Observers' assessments of a videotape were
      compared to a criterion code that defined the population of behaviors. Results
      indicated that systematic observation procedures were more accurate than
      unsystematic procedures, though this factor interacted with gender of observer
      and valence of behavior. Additionally, males tended to sample more
      representatively than females. A third finding indicated that the negatively
      valenced behavior was overestimated, whereas the neutral and positively valenced
      behaviors were accurately assessed.

PMID- 16795632
TI  - Interrupted time-series analysis and its application to behavioral data.
AB  - This paper uses a question-and-answer format to present the technical aspects of
      interrupted time-series analysis (ITSA). Topics include the potential relevance
      of ITSA to behavioral researchers, serial dependency, time-series models, tests
      of significance, and sources of ITSA information.

PMID- 16795633
TI  - The California drought: A quasi-experimental analysis of social policy.
AB  - The effect of fines for failure to conserve water during the California drought
      of 1976 to 1978 was evaluated in a retrospectively arranged multiple-baseline
      design across three San Francisco Bay area cities. The data indicated that, on a
      community level, significant savings of water occurred regardless of whether
      fines were introduced or not. However, on an individual level, fines appeared to
      have an effect on private, as opposed to commercial or industrial, consumers who
      had received at least one fine. The limitations imposed on these conclusions by
      the quasi-experimental nature of the design were highlighted. Possible reasons
      for water conservation in the absence of fines were discussed within the
      framework of stimulus control. It was suggested that an area for future research
      should be the delineation of stimulus parameters involved in producing behavior
      change in entire communities.

PMID- 16795634
TI  - Reduction of police vehicle accidents through mechaniically aided supervision.
AB  - Tachograph recorders were installed in 224 vehicles of a metropolitan police
      department to monitor vehicle operation in an attempt to reduce the rate of
      accidents. Police sergeants reviewed each tachograph chart and provided feedback
      to officers regarding their driving performance. Reliability checks and
      additional feedback procedures were implemented so that upper level supervisors
      monitored and controlled the performance of field sergeants. The tachograph
      intervention and components of the feedback system nearly eliminated personal
      injury accidents and sharply reduced accidents caused by officer negligence. A
      cost-benefit analysis revealed that the savings in vehicle repair and injury
      claims outweighed the equipment and operating costs.

PMID- 16795635
TI  - Response deprivation and reinforcement in applied settings: A preliminary
      analysis.
AB  - First-grade children engaged in seatwork behaviors under reinforcement schedules
      established according to the Premack Principle and the Response Deprivation
      Hypothesis. Across two experiments, schedules were presented to the children in a
      counter-balanced fashion which fulfilled the conditions of one, both, or neither
      of the hypotheses. Duration of on-task math and coloring in Experiment 1 and on
      task math and reading in Experiment 2 were the dependent variables. A modified
      ABA-type withdrawal design, including a condition to control for the
      noncontingent effects of a schedule, indicated an increase of on-task
      instrumental responding only in those schedules where the condition of response
      deprivation was present but not where it was absent, regardless of the
      probability differential between the instrumental and contingent responses. These
      results were consistent with laboratory findings supporting the necessity of
      response deprivation for producing the reinforcement effect in single response,
      instrumental schedules. However, the results of the control procedure were
      equivocal so the contribution of the contingent relationship between the
      responses to the increases in instrumental behavior could not be determined.
      Nevertheless, these results provided tentative support for the Response
      Deprivation Hypothesis as a new approach to establishing reinforcement schedules
      while indicating the need for further research in this area. The possible
      advantages of this technique for applied use were identified and discussed.

PMID- 16795636
TI  - Effects of informational prompts on energy conservation in college classrooms.
AB  - A multiple-baseline design was used with two target classroom groups (n = 28 and
      27) in a study to reduce electrical energy waste in college classrooms. A dittoed
      letter, signed by a faculty member, was sent to each professor in the prompt
      condition. In the letter the professor was informed that he or she taught prior
      to an unscheduled period and was asked to turn off lights following the class.
      The results showed that after the prompt, the percentage of rooms with lights
      turned off increased by 13% and 6% in each target group. A further analysis of
      the 10 classrooms that had the lowest baseline rates of turning lights off
      indicated a 30% increase after the prompt. This study indicates that a minimum
      prompt procedure was effective in reducing electrical energy waste. The further
      significance of these results are also discussed.

PMID- 16795637
TI  - Effects of training students to identify the semantic base of prose materials.
AB  - Feedback and feedback plus points toward a course grade were applied to the
      attentional behaviors (defined as the ability to identify the semantic base of
      text passages) of 30 undergraduate students participating in a reading
      comprehension development program. Correct underlining was increased, extraneous
      underlining was decreased, and postreading comprehension test scores improved as
      a result of the procedures. Scores on a standardized test of reading
      comprehension also increased significantly.

PMID- 16795639
TI  - Editorial.

PMID- 16795638
TI  - Seat belt usage: A potential target for applied behavior analysis.
AB  - Results of 1,579 observations of cars entering or exiting campus parking lots
      showed direct relationships between seat belt wearing and the intrusiveness of
      the engineering device designed to induce belt usage, and between device
      intrusiveness and system defeat. For example, all drivers with working interlocks
      or unlimited buzzer reminders were wearing a seat belt; but 62% of the systems
      with interlocks or unlimited buzzers had been defeated, and only 15.9% of the
      drivers in these cars were wearing a seat belt. The normative data indicated
      marked ineffectiveness of the negative reinforcement contingencies implied by
      current seat belt inducement systems; but suggested that unlimited buzzer systems
      would be the optimal system currently available if contingencies were developed
      to discourage the disconnection and circumvention of such systems. Positive
      reinforcement strategies are discussed that would be quite feasible for large
      scale promotion of seat belt usage.

PMID- 16795640
TI  - Flexible work schedules and family time allocation: Assessment of a system change
      on individual behavior using self-report logs.
AB  - This study assessed the effects of a flexible work schedule ("flextime") on time
      allocated to children and spouse by federal workers. Direct behavioral
      observations of family, home, and work functions were precluded because of the
      cost involved in observing many people for long periods of time. In order to
      obtain detailed individual data, participants completed hour-by-hour activity
      logs a mean of twice per week for 35 weeks. Participants received prior training
      on log completion, initial feedback on the detail of their log entries, and were
      prompted to complete the forms. Four different procedures assessing reliability
      indicated a corroboration rate of 80% with other sources. Log data were reliably
      reduced to nine categories such as "PM time with children" and 37 subcategories
      such as "time at dinner." The log data were presented in time-series form and the
      use of a quasi-experimental design showed that participants who altered their
      work schedule were able to spend more PM time with their families. The log data
      demonstrated that the capacity exists to assess closely the effects of large
      scale changes at a micro-behavioral level, but other methods are needed to make
      complex self-reporting systems less expensive and more capable of immediate
      monitoring of the intervention's effects.

PMID- 16795641
TI  - Reduction of residential consumption of electricity through simple monthly
      feedback.
AB  - Feedback has been widely used in efforts to control the consumption of
      electricity. Previous efforts, however, have used forms of feedback that seem
      economically impractical. The present study examined the effects of a feasible
      program of monthly feedback. Forty matched nonvolunteer participants were
      randomly divided into two groups: a no-contact control group and a monthly
      feedback group. In an A-B-A design, the data showed a clear decrease in
      electricity consumption for the feedback group during the feedback phase. The
      effect was maintained during a 4-mo intervention period. Withdrawal of the
      feedback was associated with a return to higher levels of electricity
      consumption.

PMID- 16795642
TI  - Effect of the good behavior game on disruptive library behavior.
AB  - A modification of the good behavior game was used to reduce disruptive behaviors
      during a weekly library period of children in a fourth-grade class. Modifications
      included student input in designing rules, attempts to state rules in positive
      terms, observation of class behavior in the experimental (library) setting as
      well as in a comparison (classroom) setting, and librarian involvement in
      instituting the game coupled with teacher involvement in delivering reinforcers.
      Reinforcers consisted of special classroom activities conducted by the teacher
      with winning team members. Modification of the good behavior game did not detract
      from its effectiveness in reducing disruptive and off-task behavior.

PMID- 16795644
TI  - A comparison of the effects of posted feedback and increased police surveillance
      on highway speeding.
AB  - A counterbalanced, reversal design was used to compare the effectiveness of
      posted feedback and increased police surveillance in reducing speeding on two
      urban highways. Drivers' speeds were measured using a concealed radar unit.
      During public posting, a large highway sign, which listed the percentage of
      drivers not speeding during the preceding week and the best record to date, was
      erected on each street. Use of the feedback sign alternated with periods of
      baseline and periods of increased police surveillance and ticketing. During
      increased police surveillance, highly visible, stationary police radar patrols
      were established along the highways for either 30 min or 60 min per day, 5 days
      per week. Results indicated that although public posting was highly effective in
      reducing the percentage of speeding drivers, increased police surveillance was
      not. Thus, since the feedback sign required only 30 min per week to maintain,
      public posting was at least 10 times more efficient in controlling speeding than
      was police surveillance and ticketing.

PMID- 16795643
TI  - Teaching self-protection to young children.
AB  - Self-protective behaviors were taught to three preschool children in order to
      prevent the opportunity for abduction. An analogue measure of self-protection was
      developed in which confederate adults approached and verbally attempted to lure
      each child from the setting, before, during, and after training. A multiple
      baseline design across subjects was used. During baseline, all the children
      displayed susceptibility to the lures. Training procedures included modeling,
      behavior rehearsal, and social reinforcement. Within 1 week after training began,
      all children displayed appropriate responses to all of the lures both in the
      training setting and in the community.

PMID- 16795645
TI  - A company-based lottery to reduce the personal driving of employees.
AB  - A company-based lottery was used to reduce the number of nonessential miles
      employees drove their personal cars each day and thereby save gasoline. Employees
      were divided into an experimental and a contrast group. The experimental design
      involved two conditions: (a) a baseline in which no consequences were attached to
      driving behavior, and (b) a month-long lottery in which the experimentals were
      rewarded for decreasing their percentage of average miles driven per day relative
      to their initial baseline average. The experimentals received an ABA order of
      conditions while the contrast group remained in baseline. The lottery condition
      consisted of four weekly lotteries and one grand drawing held at the end of the
      month. During the lottery condition, the experimentals reduced their average
      daily mileage by 11.6% relative to their initial baseline (7.85 miles per
      employee per day) while the contrast employees increased their average mileage by
      21.2%. Both groups exceeded their initial baseline averages in the return to
      baseline. The study was almost cost-effective because the experimentals' gas
      savings ($75) was within $4 of the cost of motivating them to reduce their
      mileage ($79).

PMID- 16795647
TI  - A group contingency for electricity conservation in master-metered apartments.
AB  - Two studies evaluated the effects of a group contingency on electricity
      conservation. In Study 1, residents of 166 apartment units in three towers held
      meetings and received biweekly payments of the value of electricity saved
      compared to predicted use. The group contingencies were initiated in each tower
      in a multiple-baseline design. The program produced substantial savings in one
      tower (11.2% of temperature-adjusted baseline), moderate savings in another
      (4.0%), and minimal savings in a third (1.7%). Overall, the residents saved 6.2%.
      In Study 2, residents of 255 apartment units, also in three towers, received the
      same treatment, except only 50% of the value of their savings were paid, and they
      received a one-time bonus of $5 for using >/= 10% less than baseline. Towers in
      Study 2 showed savings of 9.5%, 4.7%, and 8.3%, an average of 6.9%.

PMID- 16795646
TI  - Setting events in applied behavior analysis: Toward a conceptual and
      methodological expansion.
AB  - The contributions of applied behavior analysis as a natural science approach to
      the study of human behavior are acknowledged. However, it is also argued that
      applied behavior analysis has provided limited access to the full range of
      environmental events that influence socially significant behavior. Recent changes
      in applied behavior analysis to include analysis of side effects and social
      validation represent ways in which the traditional applied behavior analysis
      conceptual and methodological model has been profitably expanded. A third area of
      expansion, the analysis of setting events, is proposed by the authors. The
      historical development of setting events as a behavior influence concept is
      traced. Modifications of the basic applied behavior analysis methodology and
      conceptual systems that seem necessary to setting event analysis are discussed
      and examples of descriptive and experimental setting event analyses are
      presented.

PMID- 16795648
TI  - Reducing elevator energy use: A comparison of posted feedback and reduced
      elevator convenience.
AB  - The effects of two different procedures for reducing elevator energy use were
      assessed using a multiple-baseline design. In the first procedure, feedback about
      the amount of energy consumed by the elevators each week was posted on each
      elevator door. Later, signs advocating the use of stairs to save energy and
      improve health were posted next to the feedback signs. In the second procedure,
      the time required to travel between floors was increased by adding a delay to the
      elevator door closing mechanisms. Results indicated that neither feedback alone
      nor feedback plus educational signs reduced the amount of energy consumed by the
      elevators. However, use of the door delay reduced consumption by one-third in all
      elevators.A second experiment replicated the effect of the door delay on energy
      consumption and, in addition, demonstrated that the door delay also produced a
      reduction in the number of persons using the elevator. The second experiment also
      showed that, following an initial period during which a full delay was in effect,
      a gradual reduction of the delay interval resulted in continued energy
      conservation. Reduced convenience as a general strategy for energy conservation
      is discussed.

PMID- 16795649
TI  - Self-selection of standards by children: The relative effectiveness of pupil
      selected and teacher-selected standards of performance.
AB  - This study examines the effects of contingent reinforcement under conditions of
      pupil-selected and teacher-selected performance standards upon pupils' academic
      response rates. The academic response rate was measured by the number of correct
      responses emitted per session. Thirty pupils (15 second-graders and 15 third
      graders) were randomly assigned to one of three experimental groups, based on
      matched triplets. One group worked under pupil-selected standards; the second
      group worked under standards selected by the experimenter with each pupil yoked
      to a member of the pupil-selected standards groups. Both groups participated in
      the calculation of their daily earnings. The third group served as a no
      contingency control group. Baseline academic response rates on writing and math
      tasks were determined. During the experimental sessions reinforcement was
      provided in the form of points which were later traded for tangible rewards. The
      pupil-selected standards group showed a significantly greater number of correct
      responses in the writing and math tasks than the externally selected standards
      group.

PMID- 16795650
TI  - The effects of instructions and calculation procedures on observers' accuracy,
      agreement, and calculation correctness.
AB  - Although the quality of observational data is generally evaluated by observer
      agreement, measures of both observer agreement and accuracy were available in the
      present study. Videotapes with a criterion protocol were coded by 16 observers.
      All observers calculated agreement scores both on their own and their partner's
      data and on a contrived data set misrepresented as data collected by other
      observers. Compared with agreement scores calculated by the experimenter,
      observers erroneously inflated their own agreement scores and deflated the
      agreement scores on the contrived data. Half of the observers (n = 8) had been
      given instructions emphasizing the importance of accuracy during observation
      while the other half had been given instructions emphasizing interobserver
      agreement. Accuracy exceeded agreement for the former group, whereas agreement
      exceeded accuracy for the latter group. The implications are that agreement
      should be calculated by the experimenter and that the accuracy-agreement
      relationship can be altered by differential observer instructions.

PMID- 16795651
TI  - Adoption of innovations from applied behavioral research: "Does anybody care?".
AB  - Applied behavioral researchers develop useful innovative technologies
      experimentally, and yet few of these technologies enjoy widespread adoption by
      our society. This paper analyzes several instances in which government agencies
      adopted behavioral technology, identifies 10 manipulable variables that could
      increase the rate of adoption of such technological innovations, and relates them
      to the field of knowledge diffusion. Unifying theory and experimental analysis
      are lacking in that field, yet an implicit technology may exist.

PMID- 16795652
TI  - Comment on "Adoption of innovations from applied behavioral research: ;Does
      anybody care?'".

PMID- 16795653
TI  - Multiple incentives in encouraging car pool formation on a university campus.
AB  - The effects of a combined token economy and reserved parking program were
      evaluated as a means of increasing car pooling among students on a university
      campus. Following a baseline period, students in two experimental parking lots
      were notified of the availability of reserved parking and coupons redeemable for
      25 cents in merchandise for each occupant of automobiles containing two or more
      people. Two control lots also were monitored for a comparison of treatment
      effects. Results indicated variable increases in car pooling in the two
      experimental lots and no increase in the control lots. Removal of the 25-cent
      coupons from one treatment lot (reserved parking only) did not adversely affect
      rates of car pooling. An analysis of individual automobile occupancy rates among
      car poolers indicated distinct patterns of car pooling and underscored the
      importance of individual subject data analysis in the present situation. A cost
      benefit analysis indicated that even moderately effective car pool programs can
      be cost-effective on both a public and personal level.

PMID- 16795654
TI  - Correspondence between saying and doing: Some thoughts on defining correspondence
      and future directions for application.
AB  - Israel (1978) evaluated and discussed research on positive and negative verbal
      nonverbal correspondence. In the present report we attempt to delineate the
      relationship of correspondence training to two major intervention goals-producing
      (increasing) behavior and inhibiting (decreasing) behavior. The concepts of
      noncorrespondence and generalized positive correspondence are introduced. Past
      research relating to the correspondence analyses offered for the two intervention
      outcomes and possibilities for future research are discussed. The relationship of
      verbal correspondence training to the issues of response maintenance and response
      generalization is also examined.

PMID- 16795655
TI  - Simplifying continuous monitoring of multiple-response/multiple-subject classroom
      interactions.
AB  - In order to facilitate the field monitoring of three subjects interacting
      according to one or more of 18 response categories, a modified version of several
      available, but oftentimes mechanically incompatible, observational procedures was
      designed. Its continuous recording strategy, sectioned into one-minute
      observational units, enabled researchers to derive highly representative behavior
      samples, and when accompanied by the specially tailored coding form and recording
      apparatus, observers achieved over 90% agreement across all reliability sessions.
      This procedure provides applied researchers with a simple, highly reliable, and
      adaptable observation tool for continuously and simultaneously monitoring the
      behaviors of one or more subjects.

PMID- 16795656
TI  - A cautionary note on the use of probability values to evaluate interobserver
      agreement.
AB  - Proposed methods of assessing the statistical significance of interobserver
      agreements provide erroneous probability values when conducted on serially
      correlated data. Investigators who wish to evaluate interobserver agreements by
      means of statistical significance can do so by limiting the analysis to every
      k(th) interval of data, or by using Markovian techniques which accommodate serial
      correlations.

PMID- 16795657
TI  - Increasing participation and improving the quality of discussions in seventh
      grade social studies classes.
AB  - An experiment was conducted to evaluate procedures to improve classroom
      discussions in seventh-grade social studies classes. An increased number of
      students participated in discussions when rules were stated for discussions,
      students were praised for their contributions, the teacher restated or
      paraphrased students' contributions aloud or on the blackboard, the teacher
      planned an outline of discussion questions, student contributions to discussions
      were recorded and were used to determine part of the students' grades for the
      class, and discussion grades were publicly posted.The second part of the study
      focused on procedures designed to improve quality of classroom discussions.
      Students were taught to participate in discussions by providing reasons for their
      statements, comparisons between different points, or examples supporting their
      statements. As each type of contribution was taught, recorded, and counted toward
      part of the students' classroom grades, each type of contribution increased.
      Ratings of discussions by outside judges consisting of junior high school
      teachers, junior high school students, and persons experienced in conducting
      discussions, indicated that the training increased the overall quality of the
      discussions. Use of the quality training procedures, however, resulted in
      decreased levels of overall participation in discussion, a decrease that was
      reversed by the use of a group contingency for participation. Finally, the
      discussions after training seemed to be preferred by both the teacher and the
      students.

PMID- 16795658
TI  - The effects of videotape modeling and daily feedback on residential electricity
      conservation, home temperature and humidity, perceived comfort, and clothing
      worn: Winter and summer.
AB  - Two studies were conducted in all-electric townhouses and apartments in the
      winter (N = 83) and summer (N = 54) to ascertain how energy conservation
      strategies focusing on thermostat change and set-backs and other low-cost/no-cost
      approaches would affect overall electricity use and electricity used for heating
      and cooling, the home thermal environment, the perceived comfort of participants,
      and clothing that was worn. The studies assessed the effectiveness of videotape
      modeling programs that demonstrated these conservation strategies when used alone
      or combined with daily feedback on electricity use. In the winter, the results
      indicated that videotape modeling and/or feedback were effective relative to
      baseline and to a control group in reducing overall electricity use by about 15%
      and electricity used for heating by about 25%. Hygrothermographs, which
      accurately and continuously recorded temperature and humidity in the homes,
      indicated that participants were able to live with no reported loss in comfort
      and no change in attire at a mean temperature of about 62 degrees F when home and
      about 59 degrees F when asleep. The results were highly discrepant with prior
      laboratory studies indicating comfort at 75 degrees F with the insulation value
      of the clothing worn by participants in this study. In the summer, a combination
      of strategies designed to keep a home cool with minimal or no air conditioning,
      in conjunction with videotape modeling and/or daily feedback, resulted in overall
      electricity reductions of about 15% with reductions on electricity for cooling of
      about 34%, but with feedback, and feedback and modeling more effective than
      modeling alone. Despite these electricity savings, hygrothermograph recordings
      indicated minimal temperature change in the homes, with no change in perceived
      comfort or clothing worn. The results are discussed in terms of discrepancies
      with laboratory studies, optimal combinations of video-media and personal contact
      to promote behavior change, and energy policies that may be mislabeled as
      sacrificial and underestimate the effectiveness of conservation strategies such
      as those investigated in these studies.

PMID- 16795659
TI  - A behavioral analysis of incentive prompts for motivating seat belt use.
AB  - The seat belt usage of drivers was observed at the entrance to two campus parking
      lots during morning arrival times. After 11 days of baseline, fliers which
      prompted seat belt wearing were handed to drivers of incoming vehicles. At one
      parking lot all fliers offered a chance to win a prize (noncontingent rewards);
      while at the second lot only those fliers given to seat belt wearers included a
      chance to win a prize (contingent rewards). After 24 consecutive observation
      days, these interventions were removed for 14 days of withdrawal. The recording
      of vehicle license plates enabled an analysis of belt usage per individual over
      repeated exposures to the experimental conditions. At the lot with the contingent
      reward intervention, mean belt usage was 26.3% during baseline, 45.7% during
      treatment, and 37.9% during withdrawal. At the noncontingent reward lot, the mean
      percentage of belt wearing was 22.2% during baseline, 24.1% during treatment, and
      21.8% during withdrawal. The analysis of repeated exposures per individual
      verified that only contingent rewards influenced substantial increases in belt
      wearing, and showed that most of the influence occurred after the initial
      incentive prompt.

PMID- 16795660
TI  - Intervention effects and relative variation as dimensions in experts' use of
      visual inference.
AB  - Recent research indicates that when analyzing graphically presented single
      subject data, subjects trained in visual inference appear to attend to large
      changes between phases regardless of relative variation and do not differentiate
      among common intervention effect patterns. In this follow-up study, experts in
      applied behavior analysis completed a free-sort task designed to assess the
      effects of these dimensions on their use of visual inference. The results
      indicate that they tended to differentiate among common intervention effect
      patterns but did not attend to relative variation in the data.

PMID- 16795661
TI  - Contingency contracting with disadvantaged youths: Improving classroom
      performance.
AB  - This study evaluated the effects of a student-teacher contracting procedure on
      adolescent students' academic productivity. Participants were 13 youths enrolled
      in a vocational training program for disadvantaged youth and their classroom
      teacher. During the baseline conditions students were paid contingent on
      attendance alone, the system operating in the program prior to this research.
      During contracting conditions students were paid contingent on contract
      fulfillment of academic productivity goals set by mutual agreement between the
      student and teacher. Contracting and contingent pay procedures were developed
      with, and implemented by, the classroom teacher. A reversal experimental design
      showed that student's productivity more than doubled during contracting
      conditions as compared with their productivity during baseline.

PMID- 16795662
TI  - Pedestrian jaywalking under facilitating and nonfacilitating conditions.
AB  - Each year, thousands of pedestrians are killed or injured while crossing streets
      in the United States. Pedestrians who jaywalk across busy intersections increase
      their risk of being injured by an automobile. The present series of studies
      investigated pedestrian jaywalking behaviors under temporal conditions which
      appeared to control noncompliance and compliance with pedestrian walk signs. An
      intersection involving three major streets was the target site of the studies.
      The timing of walk and no-walk light sequences was different in the clockwise and
      counterclockwise direction and produced differential delays. In three separate
      studies, significantly more pedestrians jaywalked when walking in the long-delay
      as opposed to short-delay direction. Traffic planners might use these findings to
      establish safer pedestrian signal systems.

PMID- 16795663
TI  - Rewarding safety belt usage at an industrial setting: Tests of treatment
      generality and response maintenance.
AB  - An incentive program to motivate seat belt use was implemented at a large
      munitions plant. Seat belt usage was assessed daily at an entrance/exit gate of
      the industrial complex when employees arrived for work in the morning and
      departed in the afternoon. During treatment incentive fliers, which prompted seat
      belt usage and gave belt wearers opportunities to win prizes, were distributed
      only in the afternoon. Seat belt wearing increased from baseline means of 20.4%
      and 17.3% during the morning and afternoon, respectively, to averages of 55.5%
      during afternoon departures and 31.1% during morning arrivals. During follow-up,
      mean belt use dropped almost to baseline levels. Categorizing vehicles according
      to driver sex and license plate number enabled a study of belt wearing practices
      of individuals, and revealed that the incentive program influenced some drivers
      to wear their seat belts during morning arrival when incentives were not
      distributed (i.e., treatment generalization) and during a follow-up period after
      the incentives were withdrawn (i.e., response maintenance).

PMID- 16795664
TI  - Utilization analysis of a pedestrian safety training program.
AB  - A previously developed and analyzed pedestrian safety training program was used
      to teach appropriate street-crossing behaviors to kindergarteners and first
      graders. Adult crossing guards were trained to provide pedestrian safety
      instruction. Trained observers monitored the quality of instructions given by
      crossing guards and the pedestrian behavior of young children as they crossed the
      street. A multiple-baseline analysis of the effects of two training programs
      indicated that guards were able to deliver the pedestrian safety program to
      several groups of children with a high degree of competence after receiving a
      single videotape and role playing training session. Furthermore, children's level
      of appropriate street crossing increased contemporaneous to the change in guard
      behavior both on the street where training was delivered and on a second street
      where no training was previously delivered. Utilization analysis of the guard
      training program indicated that one cannot expect to produce consistently high
      levels of street-crossing behavior by implementing only the "show and tell"
      portions of the training package. Similarly, results suggested that one is
      unlikely to produce consistently high quality guard training behavior by only
      giving written instructions describing how pedestrian training should be
      administered.

PMID- 16795665
TI  - Naturalistic assessment of children's compliance to teachers' requests and
      consequences for compliance.
AB  - Naturally occurring levels of teacher commands, child compliance to those
      commands, and positive and negative teacher feedback were studied in 19 teachers
      and 130 children in kindergarten through third grade. Seventy-five of the
      children had been identified as "making a good social adjustment" to school (high
      rated) and 55 children were identified as "not making a good social adjustment"
      to school (low-rated). Results of intensive observation over a 4-wk period showed
      that: (a) individual teachers differed significantly in their overall use of
      commands; however, they did not differentially respond to high- versus low-rated
      children; (b) high-rated children were more likely to comply with commands than
      were low-rated children; (c) although the overall level of positive social
      consequences was extremely low, there was some indication that high-rated
      children were more likely to receive positive feedback for compliance than were
      low-rated children; (d) low-rated children received significantly more positive
      feedback than high-rated children for noncompliance; (e) teachers gave negative
      feedback for noncompliance at an equal level to both groups of children; and (f)
      although repeated teacher commands following noncompliance were equal across
      groups, low-rated children were exposed to significantly higher levels of
      repeated commands following compliance than were high-rated youngsters.

PMID- 16795666
TI  - Feedback interventions and driving speed: A parametric and comparative analysis.
AB  - Five experiments were conducted to assess the effects of several variables on the
      efficacy of feedback in reducing driving speed. Experiment 1 systematically
      varied the criterion used to define speeding, and results showed that the use of
      a lenient criterion (20 km/hr over the speed limit), which allowed for the
      posting of high percentages of drivers not speeding, was more effective in
      reducing speeding than the use of a stringent criterion (10 km/hr over the speed
      limit). In Experiment 2 an analysis revealed that posting feedback reduced
      speeding on a limited access highway and the effects persisted to some degree up
      to 6 km. Experiments 3 and 4 compared the effectiveness of an unmanned parked
      police vehicle (Experiment 3) and a police air patrol speeding program
      (Experiment 4) with the feedback sign and determined whether the presence of
      either of these enforcement variables could potentiate the efficacy of the sign.
      The results of both experiments demonstrated that although the two enforcement
      programs initially produced larger effects than the feedback sign, the magnitude
      of their effect attenuated over time. Experiment 5 compared the effectiveness of
      a traditional enforcement program with a warning program which included handing
      out a flier providing feedback on the number and types of accidents occuring on
      the road during the past year. This experiment demonstrated that the warning
      program produced a marked reduction in speeding and the traditional enforcement
      program did not. Furthermore, the warning program and a feedback sign together
      produced an even greater reduction in speeding than either alone.

PMID- 16795667
TI  - Evaluation of a coaching strategy to reduce swimming stroke errors with beginning
      age-group swimmers.
AB  - A coaching strategy to decrease errors in swimming strokes with swimmers who had
      not improved under "standard" coaching procedures was investigated using a
      multiple baseline design across subjects and swimming strokes. The procedure
      resulted in a large decrease in errors on swimming strokes during sessions in a
      training pool. Stimulus generalization of improved performance to normal practice
      conditions in the regular pool was observed with all but one swimmer. This
      improvement was maintained during two maintenance phases lasting approximately 2
      weeks, as well as under standard coaching conditions during at least a 2-week
      follow-up. For two swimmers, error rates on one of the strokes showed a gradual
      increase between the third and fifth week of follow-up, but brief remedial
      prompting sessions immediately corrected their performance. Some beneficial
      response generalization to other components of the stroke being trained was
      observed, but no improvements were found on untrained strokes. The error
      correction package did not disrupt practice, require excessive amounts of the
      coach's time, or necessitate the use of cumbersome apparatus. In addition, the
      coach and the swimmers considered the procedures to be effective, and expressed
      their willingness to participate in them again in the future.

PMID- 16795668
TI  - A response to "On token reinforcement and stuttering therapy: Another view on
      findings reported by Howie and Woods (1982)".
AB  - Ingham's (1983) critique of our research is based on the unwarranted assumption
      that it claimed to be a replication of Ingham and Andrews' (1973a) study. Our
      report did not claim to be a replication. Procedural differences between
      treatments do not preclude the possibility of drawing general conclusions that
      may apply to related treatments, or suggesting possible confounding variables
      that might be operating in another study. We have nevertheless dealt with each of
      Ingham's methodological objections. In general, we believe that we struck an
      acceptable compromise between the needs of clients and theoretical and research
      demands. We stand by our original conclusions, and note with satisfaction that
      Ingham concurs with our emphasis on systematic structure rather than the presence
      or absence of rewards as the crucial component of this type of stuttering
      treatment.

PMID- 16795669
TI  - Vicarious reinforcement: Expected and unexpected effects.
AB  - The primary purpose of this study was to examine the effects on one child of
      observing another child receive direct social reinforcement. In the first part of
      the study, pairs of same-sex children worked on puzzles for three sessions spaced
      2 to 3 days apart. One child was praised on a continuous schedule for
      performance, whereas the other received no praise. Although children who observed
      other children being praised increased their performance initially (as predicted
      by vicarious reinforcement and social comparison hypotheses), their performance
      decreased over time, reaching levels below their own baseline rates. In the
      second part of the study, intermittent praise delivered to the observing child
      was examined as a potential strategy to reverse the unexpected effects obtained
      in the first part of the study. Intermittent praise was found to be effective in
      reducing these effects and in producing enhanced performance. Individual data, as
      well as group data, are presented. Results are discussed in light of theoretical
      and applied issues related to the use of vicarious reinforcement in applied
      settings.

PMID- 16795670
TI  - Editorial.

PMID- 16795671
TI  - A self-instructional manual for installing low-cost/no-cost weatherization
      materials: Experimental validation with scouts.
AB  - In this study, we describe the development and evaluation of a self-instructional
      program for installing 10 low-cost/no-cost weatherization materials (e.g.,
      weatherstripping, caulking). This program was a weatherization and retrofit
      manual (WARM) providing step-by-step instructions and illustrations. Boy and Girl
      Scouts participated and used either the WARM or existing product instructions
      (EPI) to apply the materials. Scouts installed the materials properly only when
      they used the WARM.

PMID- 16795672
TI  - Behavior analysis in consumer affairs: Retail and consumer response to
      publicizing food price information.
AB  - A popular program among consumer action groups involves publicizing comparative
      food price information (CFPI) gathered from retail stores. Its significance is
      based on the assumption that publishing CFPI maximizes retail competition (i.e.,
      moderates price levels or price increases) and occasions more frugal store
      selections among consumers. We tested these assumptions during a 2-year analysis.
      Specifically, we monitored the prices of two distinct market baskets in the
      supermarkets of two midwestern cities (target and contrast cities). Following a
      lengthy baseline, we published the prices of only one of the market baskets at
      stores in the target city in the local newspaper on five different occasions. The
      results suggested that reductions in price inflation occurred for both market
      baskets at the independently operated target stores. The corporate chain stores
      were not similarly affected. In addition, surveys indicated that many consumers
      used the CFPI as a basis for store selection. Finally, the analysis included a
      discussion of the politics, economics, and future of CFPI programs.

PMID- 16795673
TI  - The influence of caloric information on cafeteria food choices.
AB  - We evaluated the effect of posting caloric information on food purchases at a
      cafeteria. Purchases of more than 14,300 entrees, vegetables, and salads by 6,970
      customers were unobtrusively monitored via the cash register inventory control
      system during 15 evening observations. A quasi-multiple-baseline design across
      food groups was used to test the additive effect of labeling the three lowest
      caloric choices for vegetables, salads, and entrees. A linear logit analysis
      confirmed that labeling increased the probability of low calorie selections for
      vegetables and salads, but not for entrees. Observations of meals purchased by a
      subsample of 413 customers indicated labeling did not change the total caloric
      content of meals. The number of customers and total sales per evening were
      unaffected by the labeling intervention. The results suggest that manipulating
      environmental cues may be an effective method for changing food purchases in a
      cafeteria, but labeling individual items may not be the best way to decrease
      total calories purchased.

PMID- 16795674
TI  - Development and analysis of a community-based resource recovery program.
AB  - Five studies were conducted over a 10-month period to determine the effectiveness
      of specific procedures in encouraging recycling among residential neighborhoods.
      Results indicated that: (a) initial levels of participation in neighborhoods were
      frequently related to housing values; (b) weekly recycling pick-ups that
      coincided with garbage collection days resulted in higher levels of participation
      than pick-ups that occurred at other times; (c) notifying homes about the
      recycling program through distributed door-to-door brochures was more effective
      than soliciting participation through newspaper ads; (d) distributing containers
      to help residents separate recyclable from nonrecyclable material proved to be an
      effective procedure, especially when combined with frequent prompting (prompting
      alone did not have much effect); and (e) procedures that facilitated the greatest
      levels of participation were not always cost-effective. The subsequent
      combination of these procedures into a package program resulted in high levels of
      neighborhood participation that were cost-effective and maintained over a 6-month
      period.

PMID- 16795675
TI  - A parent-administered program to reduce children's television viewing.
AB  - A parent-administered program to reduce television viewing of primary school-aged
      children was tested on two boys and three girls from three different families who
      were heavy viewers of television. Children were given 20 unearned tokens each
      week by their parents, which they could exchange for up to 10 hours of viewing
      time. The child earned a gold token for viewing in accordance with the rules for
      4 consecutive weeks, which was exchanged for a reward. Parents were given
      instructions to follow the program independently. Data on hours of television
      viewing, homework, and reading were recorded each day by one or both parents. A
      multiple-baseline analysis of the effects of the TV reduction program indicated
      that children reduced their baseline television viewing by more than half once
      the program was implemented, and continued to maintain these changes 6 months and
      1 year after the program was discontinued. Reading time increased for all
      children whereas effects on homework varied across children. The results support
      the effectiveness of a parent-administered program for nonbehavior problem
      children who watch excessive amounts of television.

PMID- 16795676
TI  - Effects of lines of progress and semilogarithmic charts on ratings of charted
      data.
AB  - The extent to which interrater agreement and ratings of significance on both
      changes in level and trend are affected by lines of progress and semilogarithmic
      charts was investigated. Thirteen graduate students rated four sets of charts,
      each set containing 19 phase changes. Set I data were plotted on equal interval
      charts. In Set II a line of progress was drawn through each phase on each chart.
      In Set III data points were replotted on semilogarithmic charts. In Set IV a line
      of progress was drawn through each phase of each Set III chart. A significant
      main effect on interrater agreement was found for lines of progress as well as a
      significant 2-way interaction between lines of progress and change type. Three
      main effects (chart type, lines of progress, and type of change) and a
      significant 3-way interaction were found for ratings of significance.
      Implications of these data for visual analysis of charted data are discussed.

PMID- 16795677
TI  - Practical implications of the matching law.
AB  - Many problem situations in applied settings are best conceptualized as choice
      situations. In addition, applied behavior analysts create choice situations when
      they reinforce a competing response to decrease inappropriate behavior. When such
      situations are analyzed using the matching law, variable interval (VI) schedules
      of reinforcement prove to be a superior intervention strategy regardless of the
      nature of the schedule maintaining other, less appropriate behavior. This
      conclusion is robust in that VI schedule superiority is observed in situations in
      which choice behavior is highly biased or shows pronounced undermatching as well
      as those in which the matching law holds precisely. Our analysis demonstrates the
      potential practical value of mathematical descriptions of behavior.

PMID- 16795678
TI  - Concurrent schedules and matching in applied settings: A reply to Fuqua.

PMID- 16795679
TI  - Delayed reinforcement as an indiscriminable contingency in verbal/nonverbal
      correspondence training.
AB  - We investigated the programming of generalization and maintenance of
      correspondence between verbal and nonverbal behavior in a preschool setting. Four
      children participated in a series of multiple-baseline designs. In Experiment 1,
      delayed reinforcement of verbal behavior effectively controlled maintenance of
      correspondence with previously trained responses and also resulted in
      generalization of correspondence to one untrained response. As the latter effect
      was limited, Experiment 2 was a further assessment of the effects of delayed
      reinforcement of generalization of correspondence to untrained responses, and
      consistent generalization was shown. Experiment 2 also showed that
      generalization, if lost, could be recovered through use of "booster training," in
      which the original contingencies were reinstated for a brief period. Experiment 3
      provided replications, with two additional children, of the effects of delayed
      reinforcement on maintenance of correspondence. Results are discussed in terms of
      using delayed reinforcement as an indiscriminable contingency.

PMID- 16795680
TI  - Turning the table on advice programs for parents: Using placemats to enhance
      family interaction at restaurants.
AB  - There are many opportunities in a family's daily routine to enrich the
      interactions among its members. One such opportunity arises at family
      restaurants. Surveys of restaurant personnel and customers suggested the
      possibility of enriching family interactions by redesigning indigenous materials
      such as table placemats. Accordingly, we developed Table-Talk placemats that
      provided conversational topics and illustrated games in which the entire family
      could participate. After some testing of these placemats in a preschool, a field
      experiment was conducted with families dining in restaurants. Table-Talk
      placements occasioned more social and educational dialogue among family members
      than either traditional-placemat or no-material conditions. Social validation
      ratings provided by mental health counselors and the parents suggested that Table
      Talk placemats occasioned healthy and enjoyable interactions among family
      members.

PMID- 16795681
TI  - "A simplified time-series analysis for evaluating treatment interventions": A
      rejoinder to Blumberg.

PMID- 16795682
TI  - Eye contact as an antecedent to compliant behavior.
AB  - Many experimenters and practitioners regard eye contact between instructor and
      learner as a facilitator, if not a prerequisite, to the effective instruction of
      sighted people. Without scientifically supporting the practice of demanding eye
      contact, experimenters, nonetheless, advocate its use and offer a variety of
      procedures to promote its acquisition. To justify the widespread use of demanded
      eye contact and to explain its role functionally, one experiment and data from
      six replications with nine subjects are presented. The primary experiment
      provides an empirical base for the training of eye contact prior to instruction.
      In a multiple-baseline design across two students demanded eye contact resulted
      in levels of compliance that were double and triple those of baseline. A
      tentative functional analysis of demanded eye contact is presented, followed by a
      discussion of the relationship of eye contact to attending.

PMID- 16795683
TI  - Effects of television modeling on residential energy conservation.
AB  - A combination of social marketing, communications, social learning (particularly
      modeling), and behavior analysis may provide an effective framework for behavior
      change via films and television. We used this approach in developing special
      television programs about residential energy conservation. The programs were
      tailored and directed to preselected middle-class homeowners (N = 150), and
      delivered over a public access channel of a cable TV system. The results
      indicated that after one program exposure (about 20 minutes), viewers adopted
      simple strategies modeled in the programs which led to savings of approximately
      10% on their home energy use for a substantial part of the cooling and heating
      season. Although the potential benefits to costs of large-scale media efforts
      seemed great, institutional barriers for such programs were identified. Less
      expensive, more local programs seem more viable.

PMID- 16795685
TI  - Altering contingencies to facilitate compliance with traffic light systems.
AB  - The effects of altering light pattern sequences on driver compliance at a busy,
      urban intersection were explored. The baseline light timing sequences resulted in
      only 46.8% of drivers stopping at the yellow or red lights. Using an A-B-C
      design, we altered light pattern sequences that increased the probability of
      drivers stopping at the signals to 88.8% and 98.8%. These findings indicate that
      traffic light contingencies have potent effects in influencing driver behaviors
      at busy intersections. Following completion of the study, the traffic engineer
      approved the permanence of the light timing pattern that increased traffic rule
      compliance. Accident data collected before and after the light timing changes
      indicated a reduction in automobile accidents.

PMID- 16795684
TI  - Reward induced response covariation: Side effects revisited.

PMID- 16795686
TI  - Increasing driver yielding and pedestrian signaling with prompting, feedback, and
      enforcement.
AB  - The effects of an intervention package on drivers' yielding to pedestrians and on
      pedestrians' signaling their intention to cross the street were assessed using a
      multiple baseline design. The intervention, which consisted of publicly posted
      feedback on the percentage of motorists yielding to pedestrians, small signs
      prompting pedestrians to engage in appropriate crossing behavior, and an
      enforcement program involving the use of warning tickets and feedback fliers, was
      sequentially introduced on two streets. The intervention more than doubled the
      percentage of motorists yielding to pedestrians and increased the percentage of
      pedestrians signaling their intention to cross the street to over 13% from a
      baseline level of less than 1%. Near misses involving pedestrians decreased by
      more than 50% on the narrower of the two streets.

PMID- 16795687
TI  - Effects of teacher-directed versus student-directed instruction and cues versus
      no cues for improving spelling performance.
AB  - THE PURPOSE OF THIS STUDY WAS TWOFOLD: to examine the effects of imitating
      children's spelling errors alone and in combination with visual and verbal cues
      on spelling accuracy and retention among poor spellers and to compare the
      effectiveness of student-directed versus teacher-directed spelling instruction on
      children's spelling accuracy and retention. Nine children received four
      alternating experimental treatments during a 16-week spelling program. Results
      indicated that student-directed instruction that incorporated visual and verbal
      cues was most effective in increasing children's spelling accuracy.

PMID- 16795689
TI  - A university-based incentive program to increase safety belt use: Toward cost
      effective institutionalization.
AB  - A cost-effective incentive program to increase safety belt use was implemented by
      the campus police of a large university. For each of the 3-week intervention
      periods during three consecutive academic quarters, the 22 campus police officers
      recorded the license plate numbers of vehicles with drivers wearing a shoulder
      belt. From these numbers, 10 raffle winners were drawn who received gift
      certificates donated by community merchants. Faculty and staff increased their
      belt usage markedly as a result of the "Seatbelt Sweepstakes," whereas students
      increased their belt use only slightly. A cost-effectiveness analysis indicated
      that the sweepstakes cost an average of $0.98 per each newly buckled driver.
      During each sweepstakes intervention, officers' belt usage increased
      significantly, but diminished to initial baseline levels after the final
      withdrawal of the program. Surveys of officers' opinions indicated that the
      police would accept the program demands as a regular task requirement. This
      result and the fact that program promotion and coordination were eventually taken
      over by two student organizations suggest that institutionalization of the
      "Seatbelt Sweepstakes" is feasible.

PMID- 16795688
TI  - Self-reinforcement effects: An artifact of social standard setting?
AB  - Two studies were conducted to identify mechanisms responsible for observed "self
      reinforcement" effects. In Experiment 1, using a studying task, self
      reinforcement procedures did not work when they were private (i.e., when others
      are not aware of the goals or contingencies), but did work when they were public.
      Self-delivery of consequences added nothing to the effectiveness of the
      procedure. The data suggested that public goal setting was the critical element
      in the procedure's effectiveness. In Experiment 2, an applied extension, goal
      setting alone was effective in modifying over a long time period studying
      behaviors of people with significant studying difficulties, but only when the
      goals were known to others. Overall, the two experiments make more plausible the
      view that self-reinforcement procedures work by setting a socially available
      standard against which performance can be evaluated. The procedure itself
      functions as a discriminative stimulus for stringent or lenient social
      contingencies. The application of this mechanism to other problems of applied
      significance is briefly discussed.

PMID- 16795690
TI  - Using a token-actuated timer to reduce television viewing.
AB  - A child watching an excessive amount of T.V. was provided a behavioral program
      featuring a token-actuated timer. Earned tokens were used to activate the T.V.
      for thirty-minute periods. The token-exchange system effectively reduced T.V.
      viewing and the reductions were maintained at two follow-up points. The principal
      contribution of the study is the development and evaluation of an electronically
      controlled device that was used to check the accuracy of parent-reported data.

PMID- 16795691
TI  - "Flash for life": Community-based prompting for safety belt promotion.
AB  - A community-based strategy for promoting safety belt use was field-tested in two
      adjacent rural communities, one populated by a preponderance of students,
      faculty, and staff of a major university. The intervention involved the front
      seat passenger of a stopped vehicle displaying to the driver of an adjacent,
      stopped vehicle an 11 x 14 inch flash card that read, "PLEASE BUCKLE UP-I CARE."
      If the driver buckled up, the "flasher" flipped over the card and displayed the
      message, "THANK YOU." This flash card was shown to 1,087 unbuckled drivers; 82%
      of these drivers looked at the flash card and 22% of these complied with the
      buckle-up request. Compliance was not influenced by the age or gender of the
      "flasher" (young child vs. college student), nor by the gender of the driver; but
      significantly more drivers in the university town buckled up following the flash
      card presentation (25% mean compliance in the college town vs. 14% in the other
      community). To date, over 2,000 individuals have received a buckle-up flash card
      for their own use.

PMID- 16795692
TI  - Methods of time sampling: A reappraisal of momentary time sampling and partial
      interval recording.
AB  - We compared the accuracy of momentary time sampling (MTS) and partial interval
      recording (PIR) in estimating both absolute behavioral levels and relative
      change. A computer randomly generated runs of pseudobehavior varying in duration
      and rate and simulated MTS and PIR of each run. Results indicated that when
      estimating absolute behavioral levels, duration rather than rate should be used
      as the dependent measure, and MTS is more accurate than PIR. In contrast, PIR is
      the more sensitive method for detecting relative changes in behavioral levels,
      although, at high rates, PIR tends to underestimate the degree of change.

PMID- 16795693
TI  - Training respite care providers for families with handicapped children:
      Experimental analysis and validation of an instructional package.
AB  - We conducted four experiments to evaluate a respite care training package. In
      Experiment 1, we assessed the effectiveness of an instructional manual on the
      acquisition of respite care skills and compared the relative effects of three
      different manual on the acquisition of respite care skills and compared the
      relative effects of three different manual presentation formats. Results showed
      that performance during simulated (role-played) respite care situations improved
      substantially for all six trainees following presentation of the instructional
      manual (with no significant differences between presentation formats) although
      some remedial training was necessary to achieve mastery criterion. In Experiment
      2, we evaluated the effects of the manual presented as a whole with a larger
      group of trainees and compared it to a workshop training approach. Results showed
      that both the instructional manual and workshop training approaches were
      effective, but that the former appeared to be more cost-effective. In both
      experiments, correct responding generalized to a respite care situation with a
      multiply handicapped child. In addition, several measures of social validity were
      obtained. In Experiment 3, we evaluated a simplified training and assessment
      package that could be conducted using the resources typically available to
      respite care agencies, and in Experiment 4, we demonstrated that respite care
      agency personnel could successfully implement this program.

PMID- 16795694
TI  - An experimental approach to language training in second language acquisition:
      Focus on negation.
AB  - The effect of negation training in a second language on the expression of
      negation in the native language was investigated. Four-year-old children from
      bilingual (Spanish/English) homes who showed no expressive or receptive ability
      in Spanish negation and were either proficient or nonproficient in English
      negation received Spanish negation training. Children who were proficient in
      English negation maintained correct responses in English and showed increased
      correct responses in Spanish following simultaneous training in both languages or
      in Spanish alone. Children who were nonproficient in English negation
      demonstrated a decrease in correct English responses following training in
      Spanish alone; however, children who received training in English and Spanish
      simultaneously showed increases in correct responses in both languages. These
      findings suggest that language training programs with children learning a second
      language should consider the relationship of the two language training conditions
      (simultaneous vs. independent) with the child's level of native language
      proficiency.

PMID- 16795695
TI  - Programming maintenance after correspondence training interventions with
      children.
AB  - Interventions were employed to program maintenance following correspondence
      training. The use of reinforcement of verbalization and a mixed sequence of
      procedures designed to establish indiscriminable contingencies was evaluated in
      multiple-baseline designs across subjects and behaviors. The results indicated
      that target behaviors were maintained under less intrusive interventions and in
      the absence of programmed contingencies during extended follow-up conditions. The
      results are discussed in terms of changes in reinforcement schedules established
      in maintenance interventions.

PMID- 16795696
TI  - Saying and doing: A contingency-space analysis.
AB  - Correspondences between verbal responding (saying) and nonverbal responding
      (doing) may be organized in terms of the classes of verbal/nonverbal relations
      into which particular instances of verbal/nonverbal response sequences can enter.
      Contingency spaces, which display relations among events in terms of the
      probability of one event given or not given another, have been useful in analyses
      of nonverbal behavior. We derive a taxonomy of verbal/nonverbal behavior
      relations from a contingency space that takes into account two conditional
      probabilities: the probability of a nonverbal response given a verbal response
      and that probability given the absence of the verbal response. For example,
      positive correspondence may be said to exist as a response class when the
      probability of doing is high given saying but is otherwise low. Criteria for
      other generalized classes, including negative correspondence, follow from this
      analysis.

PMID- 16795697
TI  - Computer-assisted observer training.
AB  - Computerized interactive videotapes were used to train college students to use a
      10-second partial-interval observational recording system. Students viewed
      videotapes and scored response occurrences on a computer keyboard. Incorrect
      scoring resulted in immediate computerized feedback and rescoring.Two independent
      variables, three versus seven target behaviors, and maintenance (thinning
      feedback) versus nonmaintenance (no feedback) training were compared. Average
      accuracy values across all target behaviors were consistently above 90%, and the
      lowest accuracy values obtained for most target responses typically met current
      standards for interobserver agreement. Data indicate the standard practice of
      occasional observer agreement checks may be inadequate.

PMID- 16795698
TI  - Saying and doing: A commentary on a contingency-space analysis.
AB  - This article addresses the contingency-space analysis (Matthews, Shimoff, &
      Catania, 1987) of the verbal regulation of behavior. From an applied perspective,
      the conceptualization of the relationship between saying and doing Matthews et
      al. present may be more complex than is necessary. The central issue in
      correspondence investigations is a simple one: does correspondence between what
      people say and what they do occur? The focus of this paper is on the applied and
      clinical importance of the relationship between verbalizations and relevant
      behavior and the implications for future research.

PMID- 16795699
TI  - Behavior analysis in action.

PMID- 16795700
TI  - Self-instruction: An analysis of the differential effects of instruction and
      reinforcement.
AB  - This study investigated the impact of training 9 first- and second-grade children
      to use a full self-instructional regimen, and then differentially reinforced the
      use of self-instruction only, accuracy only, or both self-instruction and
      accuracy. Three comparison children received no training in self-instruction and
      were reinforced for accuracy only. Children improved dramatically in academic
      accuracy subsequent to self-instructional training, independent of the use of
      self-instruction and of the specific behavior consequated. Children who were
      reinforced for using self-instruction did use self-instruction, and those who
      were not, did not. Comparison group children showed little improvement until
      training in problem-solving strategies was given after 9 days of reinforcement
      for accuracy. Self-instructional training is discussed as one type of event that
      increases the likelihood of accurate performance. Its effectiveness may be
      explained in terms of a teaching strategy rather than in terms of modifying
      cognitive processes.

PMID- 16795701
TI  - The efficacy of all-positive management as a function of the prior use of
      negative consequences.
AB  - Previous work suggests that an all-positive approach to child management can be
      effective. The present investigation extends these findings by examining the
      efficacy of an enhanced all-positive management system in the absence of a
      history of negative consequences. The on-task behavior and academic performance
      of 8 first- through third-grade children with academic and/or behavioral problems
      were observed in the classroom. Results indicated that, in the absence of a
      history of negative consequences, enhanced positive consequences were not
      sufficient to maintain on-task rates or academic accuracy at acceptable levels.
      The addition of negative consequences resulted in an immediate increase in on
      task behavior and academic accuracy; a primarily positive approach appeared to be
      successful in maintaining these gains following the gradual (as opposed to
      abrupt) removal of the negative consequences.

PMID- 16795702
TI  - Further generalization technology: Accounting for natural covariation in
      generalization assessment.
AB  - In recent years, the assessment of generalization effects has become a major
      priority of applied behavior analysis. In this paper we propose a set of
      procedures to increase the accuracy of generalization assessments by accounting
      for the degree of natural covariation between treated and untreated behaviors.
      Scatterplot analyses were used (a) to assess the amount of baseline and
      postbaseline covariation between behaviors, (b) to determine if the observed
      generalization effect was due to a preexisting covariation between the behaviors,
      and (c) to assess if there is a significant change in the strength of the
      relationship between the behaviors as a function of the intervention. Six
      hypothetical sets of data are used to demonstrate how these procedures provide
      more accurate and detailed generalization assessment.

PMID- 16795703
TI  - Some still-current dimensions of applied behavior analysis.
AB  - Twenty years ago, an anthropological note described the current dimensions of
      applied behavior analysis as it was prescribed and practiced in 1968: It was, or
      ought to become, applied, behavioral, analytic, technological, conceptual,
      effective, and capable of appropriately generalized outcomes. A similar
      anthropological note today finds the same dimensions still prescriptive, and to
      an increasing extent, descriptive. Several new tactics have become evident,
      however, some in the realm of conceptual analysis, some in the sociological
      status of the discipline, and some in its understanding of the necessary systemic
      nature of any applied discipline that is to operate in the domain of important
      human behaviors.

PMID- 16795705
TI  - Weak contingencies, strong contingencies, and many behaviors to change.

PMID- 16795704
TI  - The future of JABA: A comment.

PMID- 16795706
TI  - Comments on the future of applied behavior analysis.

PMID- 16795707
TI  - A thinking aid.
AB  - Writing a paper is often a process of discovering what you have to say. A small,
      inexpensive, "three-dimensional" outline of the paper is a help in guiding the
      process of discovery. New points can be accurately placed as they appear. The
      outline grows with the paper. The construction of such an outline is described.

PMID- 16795708
TI  - Correspondence between definitions and procedures: A reply to Stokes, Osnes, and
      Guevremont.
AB  - Stokes, Osnes, and Guevremont's (1987) implicit definition of correspondence
      classes appears close to ours (Matthews, Shimoff, & Catania, 1987). Their
      definition, however, is fundamentally procedural and thus may have to be modified
      as experimental methodologies are refined. The advantage of our contingency-space
      analysis is that it is independent of specific procedures and focuses attention
      on problems inherent in some procedural definitions. Specifically, a contingency
      space analysis addresses the issue of distinguishing specific instances from
      classes and reminds us that correspondence can be identified as a class only on
      the basis of observing a population of opportunities for say/do sequences in
      which the subject sometimes does not say.

PMID- 16795709
TI  - Effects of stimulus cueing on the acquisition of groundstrokes by beginning
      tennis players.
AB  - A multiple baseline design was used to examine the effects of stimulus self
      cueing on the acquisition of forehand and backhand returns by beginning tennis
      players (N = 24). A four-step verbal cueing program was introduced during
      intervention. Both the use of the technique and the successful number of returns
      were recorded. Each group showed an acceleration in skill acquisition during
      intervention, with both forehand and backhand returns improving over 45% from
      baseline conditions. Implications for the teaching of beginning tennis skills are
      discussed.

PMID- 16795710
TI  - Tokens and their economy: The Greeks had a use for them.

PMID- 16795711
TI  - Another's view of observer agreement and observer accuracy.

PMID- 16795712
TI  - The functional role of preschoolers' verbalizations in the generalization of self
      instructional training.
AB  - We examined the functional role of verbalizations in the generalization of self
      instructional training with preschoolers. Children learned to overtly self
      instruct during classroom work periods prior to covert training. Data were
      collected on children's acquisition of verbal regulation during training and on
      overt use of self-instructions in the classroom generalization setting. Results
      of a multiple baseline design across subjects indicated that treatment effects
      were evident in the training setting but did not generalize to the classroom
      until children were emitting overt self-instructions in the classroom itself. The
      production of self-verbalizations in the generalization setting was related to
      changes in correct responding, on-task behavior, and efficiency in completing
      academic work.

PMID- 16795713
TI  - Task clarification, performance feedback, and social praise: Procedures for
      improving the customer service of bank tellers.
AB  - Customer service for bank tellers was defined in terms of 11 verbal behavior
      categories. An audio-recording system was used to track the occurrence of
      behaviors in these categories for six retail banking tellers. Three behavior
      management interventions (task clarification, performance feedback, and social
      praise), applied in sequence, were designed to improve overall teller performance
      with regard to the behavioral categories targeted. Clarification was accomplished
      by providing clear delineation of the various target categories, with specific
      examples of the behaviors in each. Feedback entailed presentation of ongoing
      verbal and visual information regarding teller performance. Praise consisted of
      verbal recognition of teller performance by branch managers. Results showed that
      clarification effects emerged quickly, producing an overall increase in desired
      behaviors of 12% over baseline. Feedback and praise effects occurred more
      gradually, resulting in overall increases of 6% and 7%, respectively. A
      suspension of all procedures led to a decline in overall performance, whereas
      reinstatement of feedback and praise was again accompanied by performance
      improvement. These findings extend the generality of behavior management
      applications and help to distinguish between possible antecedent and consequent
      effects of performance feedback.

PMID- 16795714
TI  - Modifying food purchases in supermarkets with modeling, feedback, and goal
      setting procedures.
AB  - We compared several procedures designed to modify consumer food purchases with
      the objectives of reducing fat and increasing carbohydrate content, and reducing
      dollar expenditures on food. Participants were 126 volunteer community households
      which, after a 7-week baseline period, were randomly assigned to video-modeling,
      video-modeling-feedback, video-lecture, video-lecture-feedback, participant
      modeling, video-modeling-discussion, and control conditions. The main dependent
      measure was a weekly record of food purchases, convertible to percentages of
      nutrients and dollar expenditures. Results indicated that modeling-feedback and
      participant-modeling procedures were most effective (e.g., 6% reduction of total
      fat consumption, 19% dollar savings). Strategies to refine and automate modeling
      and feedback in supermarkets that may benefit consumers, corporations, and
      government are discussed.

PMID- 16795715
TI  - Evaluation of home-based programs for teaching personal safety skills to
      children.
AB  - We evaluated the efficacy of a commercially available program, the Red Flag,
      Green Flag Prevention Book, used by parents to teach their children personal
      safety skills. Children's knowledge and skills regarding the prevention of sexual
      abuse and abduction were assessed prior to, during, and after training. In one
      group, training consisted of parents using the prevention book to train their
      children. Parents of children in the second group used the prevention book with
      added instructions. Children who did not achieve criterion performance after
      training with the prevention book received behavioral skills training provided by
      the experimenter. All children acquired safety skills following behavioral skills
      training. Follow-up probes 2 months later showed skill maintenance among the
      older children. Parents reported satisfaction with the procedures and no signs of
      behavioral or emotional problems following the follow-up probe.

PMID- 16795716
TI  - The effects of advance stop lines and sign prompts on pedestrian safety in a
      crosswalk on a multilane highway.
AB  - The effects of specific signs and stop line bars designed to influence motorists
      to stop further back from the crosswalk when yielding right of way to pedestrians
      were evaluated using a reversal design. The introduction of the prompt and stop
      line reduced motor vehicle-pedestrian conflicts (near collisions) by almost 80%.
      This finding was replicated in a second experiment the following year on two
      streets using a multiple baseline design. The use of the advance stop line is now
      being incorporated by the Provincial Department of Transportation for marking
      crosswalks on multilane streets.

PMID- 16795718
TI  - Theft reduction in a grocery store through product identification and graphing of
      losses for employees.
AB  - Shoplifting and employee theft constitute a major problem for retailers. Previous
      research has described techniques for effectively reducing either type of theft
      but has not addressed the problem of thefts of unspecified origin. In a grocery
      store we evaluated the effect of identifying for employees frequently stolen
      products from three groups of items and graphing, twice weekly in the lunchroom,
      losses for the separate groups. After the products were identified and losses
      graphed, thefts from the three groups dropped from eight per day to two per day.

PMID- 16795717
TI  - On the functional role of the verbalization in correspondence training
      procedures.
AB  - We investigated the functional role of the child's and experimenter's
      verbalizations in correspondence training procedures with toy play behaviors in a
      day-care center setting. Six children participated in a multiple baseline across
      responses and/or multielement design. Baseline conditions were followed by
      reinforcement of verbalization. This resulted in little or no change in
      responding, similar to findings of previous research. Experiment I isolated the
      child's verbalization as the variable under study. With an experimenter's prompt
      and postplay reinforcement held constant, the effects of including versus
      omitting the child's verbalization were examined. A contingency-space analysis
      revealed that the presence or absence of the child's verbalization exerted no
      influence on play with the target toy. In Experiment II, a condition in which no
      experimenter's prompt occurred was added. Results suggested that the complete
      absence of any antecedent verbalization, by child or experimenter, resulted in
      much lower rates of play with the target toys. Again, however, when the
      experimenter's prompt was included, no clear difference was noted between
      conditions in which the child verbalized and conditions in which the child did
      not. These results raise doubts about the commonly held view of correspondence
      training procedures as a method of promoting self-regulation.

PMID- 16795719
TI  - Some merits and limitations of hand-held computers for data collection.

PMID- 16795720
TI  - An analysis of several variables influencing the efficacy of flash card
      instruction.
AB  - We conducted four experiments using an alternating treatments design to assess
      the influence of several variables on children's acquisition of number facts
      during one-on-one flash card instruction. In Experiment 1, we manipulated the
      order of stimulus presentation; in most cases a higher percentage of correct
      responses occurred, and mastery criterion was reached in somewhat fewer sessions,
      when a missed problem was re-presented after the next item than when problems
      were re-presented in a sequential order. In Experiment 2 a comparison of error
      contingent reprimands with no reprimands yielded similar results in favor of the
      former procedure. Experiment 3 indicated that a higher percentage of correct
      responses and more rapid acquisition occurred when the tutor and student were
      seated knee-to-knee than when a desk was positioned between them. Experiment 4
      compared the rate of learning in the presence and absence of a treatment package
      consisting of all three variables identified as leading to more rapid learning in
      the previous three experiments. Children reached criterion in less than half the
      time when the treatment package was in effect.

PMID- 16795721
TI  - The great escape: Public broadcasting goes behavioral.

PMID- 16795722
TI  - The treatment of muscle tics with dissimilar competing response practice.
AB  - Prior research has shown that muscle tics can be suppressed by the performance of
      a competing response contingent on the occurrence of the muscle tics. In an
      effort to determine whether the topography of the competing response was
      important to the muscle tic suppressing effects of contingent competing response
      practice, we evaluated the effects of a competing response that was
      topographically dissimilar to the muscle tic. Three subjects engaged in
      dissimilar competing responses contingent on the occurrence of a muscle tic; 2 of
      these subjects subsequently engaged in similar competing response practice. The
      results showed a decrease in objective measures of muscle tic frequency with the
      introduction of dissimilar competing response practice for each subject;
      subsequent exposure to similar competing response practice for 2 subjects
      resulted in no additional decrement in the level of muscle tics. These results
      suggest that the topography of the competing response may not be crucial for the
      suppression of muscle tics. Discrepancies between the objective measures of
      muscle tics and self-recorded measures are noted and discussed.

PMID- 16795723
TI  - Multiple effects of performance-contingent pay for wait-persons.
AB  - The owners of three restaurants requested help with the pay of waitpersons who
      were paid by the hour. The waitpersons asked for raises which the owners said
      they could not afford. This research changed the method of compensating
      waitpersons by making their pay contingent on dollars of food sold. Increased
      productivity and increased earnings per hour of work for all of the waitpersons
      followed the beginning of the performance-contingent pay. Most of the waitpersons
      also earned increased take-home pay when the performance-contingent pay began.
      There was little improvement in labor costs per dollar of food sold, a measure of
      benefit to the owners. The fact that benefits to workers occurred without
      benefits to owners is contrary to common views about the effects of performance
      contingent pay.

PMID- 16795724
TI  - A replication of the use of public posting in traffic speed control.
AB  - In an attempt to replicate several previous studies, a reversal design was used
      to assess the effects of publicly posted feedback on vehicle speed reduction. The
      intervention phases consisted of daily posted feedback that supplied drivers with
      either accurate or inaccurate information regarding the percentage of vehicles
      exceeding the speed limit on the road. Results from the two feedback conditions
      indicated no speed reduction in comparison to baseline levels. These results are
      discussed in light of previous studies that found strong effects for such
      feedback. Baseline levels of driver compliance and methodological differences may
      limit the effectiveness of posted feedback in reducing speeding.

PMID- 16795725
TI  - The airline lifesaver: In pursuit of small wins.

PMID- 16795726
TI  - Further comments on using hand-held computers for data collection.

PMID- 16795727
TI  - Selecting consistent vertical axis scales.

PMID- 16795728
TI  - An inexpensive event recorder.

PMID- 16795729
TI  - A teleconference seminar on applied behavior analysis.

PMID- 16795730
TI  - A prompting system for citizen involvement in fighting illegal drug activity.

PMID- 16795731
TI  - A toast to Most: Konrad Most, a 1910 pioneer in animal training.

PMID- 16795733
TI  - Burrhus Frederic Skinner (1904-1990) (a thank-you).

PMID- 16795732
TI  - Visual analysis of single-case time series: Effects of variability, serial
      dependence, and magnitude of intervention effects.
AB  - Visual analysis is the dominant method of analysis for single-case time series.
      The literature assumes that visual analysts will be conservative judges. We show
      that previous research into visual analysis has not adequately examined false
      alarm and miss rates or the effect of serial dependence. In order to measure
      false alarm and miss rates while varying serial dependence, amount of random
      variability, and effect size, 37 students undertaking a postgraduate course in
      single-case design and analysis were required to assess the presence of an
      intervention effect in each of 27 AB charts constructed using a first-order
      autoregressive model. Three levels of effect size and three levels of
      variability, representative of values found in published charts, were combined
      with autocorrelation coefficients of 0, 0.3 and 0.6 in a factorial design. False
      alarm rates were surprisingly high (16% to 84%). Positive autocorrelation and
      increased random variation both significantly increased the false alarm rates and
      interacted in a nonlinear fashion. Miss rates were relatively low (0% to 22%) and
      were not significantly affected by the design parameters. Thus, visual analysts
      were not conservative, and serial dependence did influence judgment.

PMID- 16795734
TI  - B. F. Skinner-the last few days.

PMID- 16795735
TI  - Using response cards to increase student participation in an elementary
      classroom.
AB  - The use of response cards during large-group social studies instruction was
      evaluated in a fourth-grade classroom. The experiment consisted of two
      conditions, hand raising and write-on response cards, alternated in an ABAB
      design. During baseline, the teacher called upon 1 student who had raised his or
      her hand in response to the teacher's question. During the response-card
      condition, each student in the class was provided with a white laminated board on
      which to write one- or two-word answers in response to each question asked by the
      teacher. Rate of active student response during instruction was much higher with
      response cards than with hand raising. Most students scored higher on daily
      quizzes following sessions in which response cards were used than they did on
      quizzes that followed hand-raising sessions. Response cards were preferred over
      hand raising by 19 of the 20 students in the class.

PMID- 16795736
TI  - Trends in behavior analysis in education.
AB  - The preparation of the Journal of Applied Behavior Analysis Reprint Series:
      Behavior Analysis in Education (1988) provided an opportunity to survey and
      analyze trends in the field, as reflected by publications in the journal.
      Apparently, the large volume of behavior-analytic papers on educational topics
      has been declining and its contents undergoing some interesting but not uniformly
      welcome shifts. Although the intense concern with classroom conduct has
      diminished somewhat, that topic continues to be heavily emphasized.
      Simultaneously, reports of social skills and language studies have accelerated,
      but analyses of academic performance have progressively declined. Explanations
      for the findings remain speculative, but behavior analysts are encouraged to
      address these areas of essential social need.

PMID- 16795737
TI  - Momentary time sampling as an estimate of percentage time: A field validation.
AB  - This study examined the percentage time estimates of momentary time sampling
      against the real time obtained with handheld computers in a natural setting.
      Twenty-two concurrent observations were conducted in elementary schools by one
      observer who used 15-s momentary time sampling and a second who used a handheld
      computer. Results for the six behaviors showed a close correspondence between the
      momentary time sampling percentage observation intervals and the real time
      percentage observation time, although 15-s momentary time sampling tended not to
      sample low-frequency short-duration behaviors. The results confirmed laboratory
      findings that short-interval momentary time sampling estimates percentage time
      accurately for a wide range of behavior frequencies and durations, and suggested
      that observers using momentary time sampling in a natural setting are able to
      obtain accurate data.

PMID- 16795738
TI  - Gender factors in reviewer recommendations for manuscript publication.
AB  - This study investigated whether the gender of manuscript authors affected
      reviewers' editorial decisions. Female and male reviewers for five behavioral
      journals were asked to evaluate identical manuscripts according to their usual
      criteria. Half the manuscripts were supposedly written by men and half by women.
      Male reviewers did not evaluate male- and female-authored manuscripts
      differently. Female reviewers accepted significantly more female-authored (62%)
      than male-authored (10%) manuscripts. Female-authored manuscripts were accepted
      significantly more often by female (62%) than by male (21%) reviewers.
      Information unrelated to the quality of the manuscript appears to have influenced
      reviewers' decisions. Implications for the journal review process are discussed.

PMID- 16795739
TI  - Participatory management: Maintaining staff performance in a university housing
      cooperative.
AB  - To apply behavior analysis to normal adults in non institutional settings, we may
      have to encourage their participation in the design and implementation of
      behavioral technology. This study evaluates a technology by which the members of
      a student housing cooperative manage their own staff with a minimum of
      supervision by one of the program designers. This staff management system
      consisted of prompts, self-reports, spot checks, and contingent rent reductions.
      Six resident staff members performed substantially more of their assigned tasks
      when this system was used. In addition, the management system was acceptable to
      the members, was affordable, and maintained high levels of staff performance
      during a 5-year follow-up. Participation by the members in the design and
      implementation of this system appears to have been useful in helping the behavior
      analysts to develop an unusually durable management system.

PMID- 16795740
TI  - A single-subject approach to evaluating vehicle safety belt reminders: Back to
      basics.
AB  - A single-subject ABA reversal design was applied to evaluate the effectiveness of
      a limited 8-s safety belt reminder system and two modified reminder systems (a
      delayed and second reminder) to increase the safety belt use of 13 drivers. The
      research was conducted with a specially equipped research vehicle that permitted
      the manipulation of different safety belt reminder stimuli and the unobtrusive
      recording of a driver's belt use. For 2 subjects, the limited 8-s reminder
      increased safety belt use. For another 2 subjects, the second reminder markedly
      increased belt use. Some subjects were uninfluenced by the reminder systems
      presented; others always buckled up during both baseline and intervention
      conditions. The approach and results are discussed with regard to the application
      of behavior analysis methodologies (e.g., cumulative records) and principles
      (e.g., schedules of reinforcement) to advance the utility and investigation of
      safety belt reminder systems.

PMID- 16795741
TI  - Perestroika and contingency management: Soviet agricultural reform.

PMID- 16795742
TI  - Enforcement or incentives? Promoting safety belt use among military personnel in
      the Netherlands.
AB  - During a nationwide campaign to promote safety belt use among military personnel,
      a field study was conducted at 12 different military bases in the Netherlands.
      Amount of enforcement, type of publicity, and incentive strategies were varied
      among military bases. Observations of safety belt use among servicemen in their
      personal vehicles were conducted before the campaign, immediately following the
      campaign, and 3 months later. Safety belt use increased from 65% during baseline
      to 73% directly after the campaign and to 76% 3 months later. An overall 28.6%
      increase in safety belt use (from 63% to 81%) was observed at seven bases,
      whereas no changes were found at five bases (68% on all occasions). To a large
      degree the effects were due to a 37.7% increase among young drivers. These
      results confirmed that enforcement, as well as incentives, can be effective in
      promoting safety belt use. However, treatment effects were not systematic,
      thereby complicating the interpretation of the results. Implications of these
      varied outcomes are discussed.

PMID- 16795743
TI  - Improving the driving practices of pizza deliverers: Response generalization and
      moderating effects of driving history.
AB  - A practical intervention program, targeting the safety belt use of pizza
      deliverers at two stores, increased significantly the use of both safety belts
      (143% above baseline) and turn signals (25% above baseline). Control subjects
      (i.e., pizza deliverers at a third no-intervention store and patrons driving to
      the pizza stores) showed no changes in belt or turn signal use over the course of
      7-month study. The intervention program was staggered across two pizza stores and
      consisted of a group meeting wherein employees discussed the value of safety
      belts, received feedback regarding their low safety belt use, offered suggestions
      for increasing their belt use, and made a personal commitment to buckle up by
      signing buckle-up promise cards. Subsequently, employee-designed buckle-up
      reminder signs were placed in the pizza stores. By linking license plate numbers
      to individual driving records, we examined certain aspects of driving history as
      moderators of pre- and postintervention belt use. Although baseline belt use was
      significantly lower for drivers with one or more driving demerits or accidents in
      the previous 5 years, after the intervention these risk groups increased their
      belt use significantly and at the same rate as drivers with no demerits or
      accidents. Whereas baseline belt use was similar for younger (under 25) and older
      (25 or older) drivers, younger drivers were markedly more influenced by the
      intervention than were older drivers. Individual variation in belt use during
      baseline, intervention, and follow-up phases indicated that some drivers require
      more effective and costly intervention programs to motivate their safe driving
      practices.

PMID- 16795744
TI  - Effects of public posting on driving speed in Icelandic traffic.
AB  - We replicated a study by Van Houten, Nau, and Marini (1980) that had revealed
      reductions in vehicle speeding following the posting of percentages of drivers
      not speeding on a sign at roadside. Our subjects were drivers entering a
      residential area where the speed limit changed from 90 km/hr (55.9 mph) to 60
      km/hr (37.3 mph). A total of 4,409 vehicle speeds were taken from two observation
      sessions per day for 20 consecutive weekdays. The intervention consisted of a
      single posting condition, in which a hypothetical daily percentage of drivers not
      speeding was posted on a feedback sign, followed by a double posting condition,
      in which a sign posting a best result was erected beyond the feedback sign.
      Results revealed a significant speed reduction from an average of 69.0 km/hr
      (42.9 mph) during baseline to 63.4 km/hr (39.4 mph) during single posting.
      Average speed during double posting was 62.9 km/hr (39.1 mph). The percentage of
      drivers exceeding 70 km/hr (43.5 mph) dropped from 41.0 during baseline to 20.5
      during single posting. The significant speed reductions add to the generality of
      findings of similar studies in Canada and Israel and offer possible explanations
      for the failure of feedback posting to reduce speed in the U.S.

PMID- 16795746
TI  - Automatic policing and information systems for increasing traffic law compliance.

PMID- 16795745
TI  - Behavior analysis and unsafe driving: Warning-learning trap ahead!

PMID- 16795747
TI  - The buckle-up promise card: A versatile intervention for large-scale behavior
      change.

PMID- 16795748
TI  - The study of consumer behavior and social validity: An essential partnership for
      applied behavior analysis.

PMID- 16795749
TI  - Computer-programmed instruction: The relation of required interaction to
      practical application.
AB  - Computers were used to evaluate the effects of supplying answers to programmed
      instruction frames. A group experimental design compared passive reading, covert
      responding to frame blanks, and actively typing answers to blanks with and
      without immediate confirmation of correctness. Effects of a 315-frame program,
      teaching elements of programmed instruction design, were evaluated by analyzing
      answers to posttest generalization questions and an application test. Results
      strongly supported the effectiveness of requiring the student to supply fragments
      of a terminal repertoire while working through a program. Students who could
      either covertly respond to frame blanks or who were required to type frame
      answers performed significantly better on the frame generalization posttest and,
      more importantly, carefully followed program rules when preparing elements of a
      new instructional program.

PMID- 16795751
TI  - The limits of technological talk.

PMID- 16795750
TI  - Deconstructing "technological to a fault".

PMID- 16795752
TI  - Applied behavior analysis as technological science.

PMID- 16795753
TI  - We need a new model of technology.

PMID- 16795754
TI  - Tacting "to a fault".

PMID- 16795756
TI  - Pinpointing the technological fault in applied behavior analysis.

PMID- 16795755
TI  - Technological behavior analysis and societal impact: A human services
      perspective.

PMID- 16795757
TI  - Marketing behavior analysis requires different talk.

PMID- 16795758
TI  - The recycling solution: How I increased recycling on Dilworth Road.

PMID- 16795759
TI  - Some values guiding community research and action.
AB  - The dual purposes of applied research-contributing to understanding and
      improvement-are only partially served by method systems that encourage studying
      (with increasing precision) a narrow range of questions of modest societal
      importance. To optimize contributions to challenging societal problems, a field's
      cherished standards should be adapted to support more adventuresome forms of
      community research and action. This paper outlines 10 values for community
      research and action, based on insights from the fields of behavioral and
      community psychology. These values-reflect the goals and challenges of
      establishing collaborative relationships with research participants, determining
      research goals and methods, designing and disseminating interventions,
      communicating research findings, and advocating for community change. Critical
      challenges are outlined, and implications for the field and its clients are
      discussed.

PMID- 16795760
TI  - Caveats on values guiding community research and action.

PMID- 16795761
TI  - Ya shoulda, oughta, wanna, or, laws of behavior and behavioral community
      research.

PMID- 16795762
TI  - Avoiding the countercontrol of applied behavior analysis.

PMID- 16795764
TI  - Reappraisal of momentary time sampling and partial-interval recording.

PMID- 16795763
TI  - A simple BASIC program to generate values for variable-interval schedules of
      reinforcement.
AB  - A BASIC program to generate values for variable-interval (VI) schedules of
      reinforcement is presented. A VI schedule should provide access to reinforcement
      with a constant probability over a time horizon. If the values in a VI schedule
      are calculated from an arithmetic progression, the probability of reinforcement
      is positively correlated with the time since the last reinforcer was delivered.
      Fleshler and Hoffman (1962) developed an iterative equation to calculate VI
      schedule values so that the probability of reinforcement remains constant. This
      easy-to-use program generates VI schedule values according to the Fleshler and
      Hoffman equation, randomizes the values, and saves the values in ASCII to a disk
      file.

PMID- 16795765
TI  - Expanding the notion of teachers' rights: Access to tools that work.

PMID- 16795766
TI  - Why aren't effective teaching tools widely adopted?

PMID- 16795767
TI  - School reform: Independent variable or dependent measure?

PMID- 16795768
TI  - Disseminating an effective educational technology.

PMID- 16795769
TI  - Applied behavior analysis for educators: Teacher centered and classroom based.

PMID- 16795770
TI  - Potential contributions of performance science to education.

PMID- 16795771
TI  - Precision teaching: Discoveries and effects.

PMID- 16795772
TI  - Reflections on PSI: Good news and bad.

PMID- 16795773
TI  - L'enfant terrible meets the educational crisis.

PMID- 16795774
TI  - Natural reinforcement: A way to improve education.

PMID- 16795776
TI  - Is back to nature always best?

PMID- 16795775
TI  - The reform of education is at least a four-legged program.

PMID- 16795777
TI  - Should we train applied behavior analysts to be researchers?

PMID- 16795778
TI  - Teacher proposes, student disposes.

PMID- 16795779
TI  - Managing our own behavior: Some hidden issues.

PMID- 16795780
TI  - The need to train more behavior analysts to be better applied researchers.

PMID- 16795781
TI  - Discrimination and generalization.

PMID- 16795782
TI  - Follow-up commentary on training behavior analysts.

PMID- 16795783
TI  - Total quality management and organizational behavior management: An integration
      for continual improvement.

PMID- 16795784
TI  - Opportunities for applied behavior analysis in the total quality movement.

PMID- 16795785
TI  - A sequential learning analysis of decisions in organizations to escalate
      investments despite continuing costs or losses.
AB  - Reinforcement process may underlie decisions frequently found in organizations to
      escalate investments of time, money and other resources in strategies (e.g.,
      product development, capital investment, plant expansion) that do not result in
      immediate reinforces. Whereas cognitive biases have been proffered in previous
      explanations, the present analysis suggested that this persistence is a form of
      resistance to extinction arising from experiences with past investments that were
      variably reinforced. This explanation was examined in two experiments by varying
      the pattern of returns and losses subjects experienced for investment decisions
      prior to experiencing a series losses. Consistent with the proposed explanation,
      two conditions resulted in higher levels of recommitment during continuous
      losses: (a) training using a variable schedule of partial reinforcement, and (b)
      no training on the task. Results indicate that behavior analysis can be used to
      understand and control situations in organizations that are prone to escalation,
      such as investments in the research and development of new product lines and
      extensions of further loans to customers.

PMID- 16795786
TI  - The organization of behavior.

PMID- 16795787
TI  - The basic importance of escalation.

PMID- 16795788
TI  - Going beyond with Bayesian updating.

PMID- 16795789
TI  - Reciprocal peer management: Improving staff instruction in a vocational training
      program.
AB  - To test the feasibility and utility of involving peers as sources of feedback, 6
      subjects, instructors in a vocational program for adults with mental retardation,
      participated in a staff training and management program. Subjects' teaching
      interactions were assessed during baseline, in-service training (on effective
      teaching), return-to-baseline, peer management, and follow-up phases. Peer
      management was introduced in multiple baseline fashion across pairs of subjects.
      Members of each pair were trained to monitor peer teaching, to record and graph
      data, to provide feedback, and to set goals with the peer. Each pair then
      performed these procedures on the job for several weeks, during which time 4 of
      the 6 subjects increased their use of effective teaching methods (over baseline).
      However, inconsistencies in the magnitude and durability of these increases
      require that the study be viewed as inconclusive, although it has heuristic value
      as a promising model for involving co-workers in staff management programs.

PMID- 16795790
TI  - The role of applied behavior analysis in zoo management: Today and tomorrow.

PMID- 16795791
TI  - Behavioral momentum in college basketball.
AB  - Three classes of events were scored from videotapes of 14 college basketball
      games during the 1989 National Collegiate Athletic Association tournament:
      reinforcers (such as points and favorable turnovers), adversities (such as missed
      shots, unfavorable turnovers, and fouls), and responses to adversities (favorable
      or unfavorable outcomes of the first possession of the ball following an
      adversity). Within-game and within-team analyses of these data supported three
      findings. First, a team's favorable response to an adversity generally increased
      as the rate of reinforcement increased 3 min preceding the adversity. Second,
      basketball coaches called time-out from play when being outscored by their
      opponents an average of 2.63 to 1.0. Third, calling time-outs from play appeared
      to be an effective intervention for reducing an opponent's rate of reinforcement.
      Rates of reinforcement during the 3 min immediately after a time-out were nearly
      equal for both teams. Results are discussed within a behavioral momentum
      framework.

PMID- 16795792
TI  - Effects of reinforcer rate and reinforcer quality on time allocation: Extensions
      of matching theory to educational settings.
AB  - We examined how 3 special education students allocated their responding across
      two concurrently available tasks associated with unequal rates and equal versus
      unequal qualities of reinforcement. The students completed math problems from two
      alternative sets on concurrent variable-interval (VI) 30-s VI 120-s schedules of
      reinforcement. During the equal-quality reinforcer condition, high-quality
      (nickels) and low-quality items ("program money" in the school's token economy)
      were alternated across sessions as the reinforcer for both sets of problems.
      During the unequal-quality reinforcer condition, the low-quality reinforcer was
      used for the set of problems on the VI 30-s schedule, and the high-quality
      reinforcer was used for the set of problems on the VI 120-s schedule. Equal- and
      unequal-quality reinforcer conditions were alternated using a reversal design.
      Results showed that sensitivity to the features of the VI reinforcement schedules
      developed only after the reinforcement intervals were signaled through countdown
      timers. Thereafter, when reinforcer quality was equal, the time allocated to
      concurrent response alternatives was approximately proportional to obtained
      reinforcement, as predicted by the matching law. However the matching relation
      was disrupted when, as occurs in most natural choice situations, the quality of
      the reinforcers differed across the response options.

PMID- 16795793
TI  - Increasing recycling in office environments: The effects of specific, informative
      cues.
AB  - We investigated the effects of prompts on the recycling behavior of approximately
      217 faculty, staff, and graduate students in two academic departments of a large
      university. During the intervention, two signs were posted in each department.
      One sign prompted recycling (posted above the recycling receptacle), and the
      other sign prompted proper disposal of trash (posted above the trash receptacle).
      Results of a multiple baseline design across the two departments indicated that
      the sign prompt increased recycling behavior. Installation of the sign prompts in
      close proximity to receptacles in Department A resulted in a 54% improvement over
      baseline. Posting of sign prompts over containers 4 m apart in Department B
      resulted in a 17% improvement, whereas positioning the signs and receptacles in
      close proximity resulted in a 29% improvement over baseline.

PMID- 16795794
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      November, 1992.

PMID- 16795795
TI  - JEAB, November '92: What's in it for the JABA reader?

PMID- 16795796
TI  - Further reappraisal of momentary time sampling and partial-interval recording.

PMID- 16795797
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      January 1993.

PMID- 16795798
TI  - The collateral effects of behavioral interventions: Applied implications from
      JEAB, January 1993.

PMID- 16795799
TI  - Automated data acquisition through time-lapse videotape recording.

PMID- 16795800
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      March 1993.

PMID- 16795801
TI  - Applied implications of current JEAB research on derived relations and delayed
      reinforcement.

PMID- 16795802
TI  - Taking stock: The first 25 years of the Journal of Applied Behavior Analysis.
AB  - Some aspects of the performance of the Journal of Applied Behavior Analysis
      (JABA) are described on the occasion of the journal's 25th anniversary.
      Comparative circulation data are presented. JABA's influence on the scientific
      community is measured by examining the citation history of articles that it has
      published, with attention to both frequency and source of the citations. The
      influence that other journals have on JABA's authors is assessed through an
      analysis of citations made by those authors in this journal's reference lists.
      The citation history indicates clearly that JABA has made substantial
      contributions toward producing methods useful in coping with a wide variety of
      problem behaviors, from profound developmental disabilities (such as autism) to
      the simpler behavioral problems that interfere with normal functioning in home
      and at school. Recently, the journal has devoted many issues and parts of issues
      to special topics, in a concerted effort to reflect the increasing breadth of
      applied behavioranalysis.

PMID- 16795803
TI  - Publication trends in 25 years of the Journal of Applied Behavior Analysis.
AB  - All articles published in the first 25 years of JABA (1968 to 1992) were reviewed
      to classify the percentage of articles published in the following categories: (a)
      type of article, (b) subjects, (c) setting, (d) behavior-change agent, (e) target
      behavior, (f) use of basic principles, and (g) miscellaneous procedures. Overall
      percentages and trends are reported in each category. Results indicate an
      increase in the percentage of articles with participants and target behaviors in
      developmental disabilities and a decrease in the percentage of studies targeting
      academic behavior, verbal behavior, and other child behavioral excesses. The most
      frequent setting continues to be a school; however, there is a clear trend
      towards community and other naturalistic settings. Results also highlight the
      increasing complexity and multicomponent nature of JABA interventions. Potential
      implications for future applications are discussed.

PMID- 16795804
TI  - Snapshots of JABA.

PMID- 16795805
TI  - Behavioral roots of JABA's editors and associate editors.

PMID- 16795806
TI  - Authors with 10 or more articles published in JABA.

PMID- 16795807
TI  - Remembrances of issues past: Celebrating JABA's 25th anniversary.

PMID- 16795808
TI  - An editor's recollections: 1978-1980.

PMID- 16795809
TI  - Foundation and empire.

PMID- 16795810
TI  - Editors are students of JABA.

PMID- 16795811
TI  - Living at the center of the universe.

PMID- 16795812
TI  - Thinking big.

PMID- 16795813
TI  - How time flies!

PMID- 16795814
TI  - A brief history of applied behavior analysis at the University of Washington.

PMID- 16795815
TI  - A brief, selective history of the Department of Human Development and Family Life
      at the University of Kansas: The early years.

PMID- 16795816
TI  - Applied behavior analysis at West Virginia University: A brief history.
AB  - The development of an emphasis on applied behavior analysis in the Department of
      Psychology at West Virginia University is traced. The emphasis began primarily in
      the early 1970s, under the leadership of Roger Maley and Jon Krapfl, and has
      continued to expand and evolve with the participation of numerous behavior
      analysts and behavior therapists, both inside and outside the department. The
      development has been facilitated by several factors: establishment of a strong
      behavioral emphasis in the three Clinical graduate programs; change of the
      graduate program in Experimental Psychology to a program in basic Behavior
      Analysis; development of nonclinical applied behavior analysis within the
      Behavior Analysis program; establishment of a joint graduate program with
      Educational Psychology; establishment of a Community/Systems graduate program;
      and organization of numerous conferences. Several factors are described that seem
      to assure a stable role for behavior analysis in the department: a stable and
      supportive "culture" within the department; American Psychological Association
      accreditation of the clinical training; a good reputation both within the
      university and in psychology; and a broader community of behavior analysts and
      behavior therapists.

PMID- 16795818
TI  - A brief overview of the history of Western Michigan University's behavioral
      programs.

PMID- 16795817
TI  - The behavior analysis and therapy program at southern illinois university at
      carbondale.

PMID- 16795819
TI  - Promoting principals' managerial involvement in instructional improvement.
AB  - Studies of school leadership suggest that visiting classrooms, emphasizing
      achievement and training, and supporting teachers are important indicators of the
      effectiveness of school principals. The utility of a behavior-analytic program to
      support the enhancement of these behaviors in 2 school principals and the impact
      of their involvement upon teachers' and students' performances in three classes
      were examined in two experiments, one at an elementary school and another at a
      secondary school. Treatment conditions consisted of helping the principal or
      teacher to schedule his or her time and to use goal setting, feedback, and
      praise. A withdrawal design (Experiment 1) and a multiple baseline across
      classrooms (Experiment 2) showed that the principal's and teacher's rates of
      praise, feedback, and goal setting increased during the intervention, and were
      associated with improvements in the academic performance of the students. In the
      future, school psychologists might analyze the impact of involving themselves in
      supporting the principal's involvement in improving students' and teachers'
      performances or in playing a similar leadership role themselves.

PMID- 16795820
TI  - Courteous service: Its assessment and modification in a human service
      organization.
AB  - We evaluated strategies to increase behaviors associated with courteous provision
      of service by 3 staff members of a human service agency. Training included
      written instructions, practice, and performance feedback. A lottery procedure was
      introduced to maintain courteous service after training. The results of a
      multiple baseline design across the 3 participants showed marked increases in
      courteous behaviors following training. These effects were maintained at 3-, 5-,
      and 8-month follow-ups. Consumers' satisfaction with service also increased.
      These findings suggest that simple training and reinforcement procedures can
      enhance courtesy afforded those who receive service from public and nonprofit
      organizations.

PMID- 16795821
TI  - Office paper recycling: A function of container proximity.
AB  - We investigated the effects of proximity of containers on pounds of office paper
      recycled and not recycled by 25 employees. During a memo and central container
      condition, one container for recyclable paper was provided; in a memo and local
      container condition, desktop recycling bins, announced by memo, were successively
      introduced across administrative, office, and instructional settings using a
      multiple baseline design. Only 28% of paper was recycled in the central container
      condition, but when recycling containers were placed in close proximity to
      participants, 85% to 94% of all recyclable paper was recycled. Follow-up
      assessments, conducted 1, 2, 3, and 7 months after all settings received local
      recycling containers, showed that 84% to 98% of paper was recycled. Providing
      desktop recycling containers was a cost-effective procedure with long-term
      maintenance and program survival.

PMID- 16795823
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      July 1993.

PMID- 16795822
TI  - Effects of active student response during error correction on the acquisition,
      maintenance, and generalization of science vocabulary by elementary students: A
      systematic replication.
AB  - We compared active student response (ASR) error correction and no-response (NR)
      error correction while teaching science terms to 5 elementary students. When a
      student erred on ASR terms, the teacher modeled the definition and the student
      repeated it. When a student erred on NR terms, the teacher modeled the definition
      while the student looked at the vocabulary card. ASR error correction was
      superior on each of the study's seven dependent variables.

PMID- 16795825
TI  - Applied behavior analysis and school psychology.

PMID- 16795826
TI  - Effects of response cards on student participation and academic achievement: A
      systematic replication with inner-city students during whole-class science
      instruction.
AB  - We evaluated the use of response cards during science instruction in a fifth
      grade inner-city classroom. The experiment consisted of two methods of student
      participation-hand raising and write-on response cards-alternated in an ABAB
      design. During hand raising, the teacher called upon 1 student who had raised his
      or her hand in response to the teacher's question. During the response-card
      condition, each student was provided with a laminated board on which to write one
      or two-word answers in response to each question asked by the teacher. Frequency
      of active student response was 14 times higher with response cards than with hand
      raising. All 22 students scored higher on next-day quizzes and on 2-week review
      tests that followed instruction with response cards than they did on quizzes and
      tests that covered facts and concepts taught with the hand-raising procedure.

PMID- 16795824
TI  - Applied implications of theory and research on the nature of reinforcement.

PMID- 16795827
TI  - Using student-managed interventions to increase homework completion and accuracy.
AB  - We examined the effectiveness of self-managed individual and group contingency
      procedures in improving the completion and accuracy rates of daily mathematics
      homework assignments. A group of sixth-grade students having homework
      difficulties in mathematics were selected for the study. There was substantial
      improvement in the amount of homework completed over baseline for a majority of
      the students, whereas the results for accuracy were mixed. Students who
      participated in the self-management training made significant gains on
      standardized measures of academic achievement and curriculum-based measures of
      classroom performance. Parents also reported significantly fewer problems
      associated with homework completion following the intervention. Students who were
      allowed to select their own performance goals made superior improvements in the
      number of homework assignments returned compared to students who were given a
      specified goal by the classroom teacher. Parents, subjects, and the classroom
      teacher responded positively on consumer satisfaction measures following
      termination of the study.

PMID- 16795829
TI  - Current research on functional analysis methodologies: An introduction.

PMID- 16795828
TI  - Editor's note.

PMID- 16795830
TI  - The significance and future of functional analysis methodologies.
AB  - Iwata, Dorsey, Slifer, Bauman, and Richman (1982) presented the first
      comprehensive and standardized methodology for identifying operant functions of
      aberrant behavior. This essay discusses the significance functional analysis has
      had for applied behavior analysis. The methodology has lessened the field's
      reliance on default technologies and promoted analysis of environment-behavior
      interactions maintaining target responses as the basis for selecting treatments.
      It has also contributed to the integration of basic and applied research. Future
      directions for this research are suggested.

PMID- 16795831
TI  - Functional assessment: Contributions and future directions.
AB  - Functional assessment is at once redefining the standards for clinical
      interventions and reemphasizing the importance of studying basic behavioral
      mechanisms. This commentary describes one perception of what we are learning from
      current research on functional assessment and suggests directions for the future.

PMID- 16795832
TI  - Functional analysis methodology: Some closing comments.
AB  - Functional analysis methodologies have emerged as powerful tools in research on
      the assessment and treatment of severe behavior disorders. Although the defining
      feature of these approaches is the systematic identification of environmental
      determinants of behavior, research methodology has varied widely with respect to
      the arrangements used to demonstrate experimental control as well as the types of
      variables subject to analysis. This commentary summarizes methodological and
      conceptual issues that have been raised in current research and offers some
      suggestions for their resolution.

PMID- 16795833
TI  - A comparison of three interventions for increasing oral reading performance:
      Application of the instructional hierarchy.
AB  - The instructional hierarchy is a behavior-analytic model that links level of
      academic skill development (i.e., acquisition, fluency, generalization,
      adaptation) with appropriate instructional techniques. The present study used the
      instructional hierarchy to compare the effects of three instructional
      interventions (listening passage preview, subject passage preview, and taped
      words) on subjects' oral reading performance on word lists and passages. Subjects
      were 4 male students with learning disabilities who ranged in age from 8 years 10
      months to 11 years 11 months. A multielement design was used to compare the
      effects of the three interventions to each other and to baseline. Results
      indicated that the listening passage preview intervention (which contained
      modeling, drill, and generalization components) produced the largest performance
      gains. The implications of these results for selecting academic interventions
      based on the instructional hierarchy are discussed.

PMID- 16795834
TI  - Effects of imposed postfeedback delays in programmed instruction.
AB  - Imposed postfeedback delays promote discrimination training; the present
      experiments determined whether they also improve performance in programmed
      instruction. In two experiments, college students completed 45 sets of Holland
      and Skinner's (1961) programmed text on behavior analysis in a computerized
      format in a three-component multiple schedule. In Experiment 1, the conditions
      were (a) no delay between questions, (b) a 10-s delay after each question
      (noncontingent delay), and (c) a 10-s delay after each question answered
      incorrectly (contingent delay). Noncontingent delay produced better performance
      than no delay and contingent delay. To determine whether performance increased in
      the noncontingent delay condition because subjects studied the material during
      delay periods, Experiment 2 tested three conditions: (a) no delay between
      questions, (b) a 10-s delay after each question (noncontingent delay), and (c) a
      10-s delay after each question with the screen blank during the delay period.
      Noncontingent delay produced better performance than no delay, but there was no
      difference in performance between no delay and noncontingent delay with blank
      screen. Hence, noncontingent delay improved performance because students used
      delay periods to study. Furthermore, subjects preferred noncontingent delay to
      the other conditions, and session time increased only slightly.

PMID- 16795836
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      September 1993.

PMID- 16795835
TI  - The effects of attentional shift training on the execution of soccer skills: A
      preliminary investigation.
AB  - One of the most important skills in soccer is the ability to respond quickly and
      accurately to the changing demands of the competitive environment (i.e., position
      of ball, teammates, opponents). A multiple baseline design across 4 male
      collegiate soccer players was used to determine the effectiveness of an
      attentional training program on the execution of targeted soccer skills. The
      treatment included information and laboratory attentional shift exercises
      followed by practice of attentional shifting skills on the execution of different
      soccer exercises. Following treatment, the accuracy of execution of the
      experimental soccer drill improved.

PMID- 16795837
TI  - The ABCs of JEAB, September 1993.

PMID- 16795838
TI  - Toward greater integration of basic and applied behavioral research: An
      introduction.

PMID- 16795839
TI  - Limited matching on concurrent-schedule reinforcement of academic behavior.
AB  - Three adolescent students with special educational needs were given a choice
      between completing one of two available sets of math problems. Reinforcers
      (nickels) across these alternatives were arranged systematically in separate
      experimental phases according to three different concurrent variable-interval
      schedules (reinforcement ratios of 2:1, 6:1, and 12:1). Time allocated to the two
      stacks of math problems stood in linear relationship to the reinforcement rate
      obtained from each stack, although substantial undermatching and bias were
      observed for all subjects. However, changes in the schedules were not followed by
      changes in allocation patterns until adjunct procedures (e.g., changeover delays,
      limited holds, timers, and demonstrations) were introduced. The necessity of
      adjunct procedures in establishing matching in applied situations is discussed as
      a limitation to quantitative applications of the matching law in applied behavior
      analysis.

PMID- 16795840
TI  - Preference for reinforcers under varying schedule arrangements: A behavioral
      economic analysis.
AB  - The field of behavioral economics combines concepts from economics and operant
      conditioning to examine the influence of schedules or price on preference for
      reinforcers. Three case studies are reported in which behavioral economic
      analyses were used to assess relative preference for reinforcers shown by people
      with intellectual disabilities when schedule requirements varied. The studies
      examined (a) preference for different reinforcers, (b) substitutability of
      reinforcers, and (c) changes in preference as a function of schedule
      requirements.

PMID- 16795841
TI  - Behavioral contrast in a two-option analogue task of financial decision making.
AB  - The effects of an alternative course of action on sustained escalation and
      persistence in the face of failure was investigated using a computerized stock
      investment task. Subjects invested in "stock" in two "markets" that yielded
      returns according to two-component multiple variable-interval schedules. Both
      markets yielded equal but intermittent return rates during the first phase. In
      the second phase, one market ceased to yield returns, while the return rate for
      the other market was unchanged. During the second phase, behavioral contrast
      effects were evident. Investing in the market that ceased to yield returns
      dropped precipitously, and investing in the unchanged market increased
      significantly. Although the behavior may be economically "irrational," it is
      predictable from the matching law and shows that interactions among a history of
      intermittent returns in a course of action, current return rate, and currently
      available alternative courses of action are important determinants of persisting
      in, or withdrawing from, a failing course of action.

PMID- 16795842
TI  - Behavioral momentum and stimulus fading in the acquisition and maintenance of
      child compliance in the home.
AB  - The provision of a series of requests to which compliance is highly likely (high
      probability requests) immediately antecedent to low-probability requests has been
      used to establish behavioral momentum of compliance. We evaluated a fading
      procedure for maintaining high levels of compliance obtained with high
      probability requests. Fading involved a systematic reduction in the number of
      high-probability requests and an increase in the latency between the high- and
      low-probability requests. High levels of compliance for both "do" and "don't"
      requests were maintained for 16 weeks in a 5-year-old boy with developmental
      disabilities after the high-probability request sequence was faded. Similar
      maintenance was obtained for "do" requests in a 15-year-old girl with
      developmental disabilities. For this subject, however, the high-probability
      request sequence was ineffective with "don't" requests. When "don't" requests
      were phrased as "do" requests, the high-probability request sequence produced
      high levels of compliance to the low-probability request. High levels of
      compliance to these "do" requests were maintained for 16 weeks after the high
      probability request sequence was faded.

PMID- 16795843
TI  - Correlation between self-reported rigidity and rule-governed insensitivity to
      operant contingencies.
AB  - Adults were selected on the basis of their scores on the Scale for Personality
      Rigidity (Rehfisch, 1958a). Their scores served as a measure of hypothesized rule
      governance in the natural environment. Experiment 1 studied the effects of
      accurate versus minimal instructions and high versus low rigidity on performance
      on a multiple differential-reinforcement-of-low-rate (DRL) 4-s fixed-ratio (FR)
      18 schedule. When the schedule was switched to extinction, accurate instructions
      and high rigidity were associated with greater perseveration in the response
      pattern subjects developed during the reinforcement phase. In Experiment 2, the
      effects of rigidity and of accurate versus inaccurate instructions were studied.
      Initially, all subjects received accurate instructions about an FR schedule. The
      schedule was then switched to DRL, but only half of the subjects received
      instructions about the DRL contingency, and the other half received FR
      instructions as before. Accurate instructions minimized individual differences
      because both high and low scorers on the rigidity scale earned points in DRL.
      However, when inaccurate instructions were provided, all high-rigidity subjects
      followed them although they did not earn points on the schedule, whereas most low
      rigidity subjects abandoned them and responded appropriately to DRL. The
      experiments demonstrate a correlation between performances observed in the human
      operant laboratory and a paper-and-pencil test of rigidity that purportedly
      reflects important response styles that differentiate individuals in the natural
      environment. Implications for applied research and intervention are discussed.

PMID- 16795844
TI  - Nodality effects during equivalence class formation: An extension to sight-word
      reading and concept development.
AB  - Three students with moderate disabilities were taught to read and match-to-sample
      sight words comprising stimulus sets based upon the four food groups. We taught
      students conditional discriminations within four four-member sets using a single
      sample/four-comparison procedure. Students were taught A-B, B-C, and C-D
      conditional discriminations for each of the four potential stimulus classes.
      Subsequent probes tested for relations based upon symmetry and one-node and two
      node transitivity. The performances for all students indicated that symmetric
      relations emerged before one-node transitive relations, and that one-node
      transitive relations emerged before two-node transitive relations. These results
      are consistent with a pattern of responding, referred to as a "nodality effect,"
      in which relations with fewer nodes are demonstrated prior to the demonstration
      of relations with a greater number of nodes. These results extend this area of
      research to sight-word reading for students with moderate disabilities.

PMID- 16795845
TI  - Treatment of escape-maintained aberrant behavior with escape extinction and
      predictable routines.
AB  - We evaluated the effects of two daily activity schedules on 2 participants' rates
      of aberrant behavior and their compliance. Functional analysis identified the
      operant function of the participants' aberrant behaviors to be escape from tasks.
      Participants were taught to use stimuli contained in daily schedules, and were
      tested based on a modified stimulus-equivalence model that consisted of flash
      cards and activity schedules comprised of words or photographs that corresponded
      to the participants' daily activities. On pretests, the participants demonstrated
      simple and conditional discriminations with the photographs but not with the
      printed stimuli. A time-delay procedure was used to teach the participants to
      name the flash cards. Following training, the printed activity schedules
      corresponded to lower rates of problem behavior and higher rates of compliance
      than the photographic activity schedules. Performance on posttests indicated the
      establishment of functional classes of stimuli involving the flash cards and
      activity schedules even though this type of correspondence was not directly
      trained.

PMID- 16795846
TI  - Self- and cross-citations in the Journal of Applied Behavior Analysis and the
      Journal of the Experimental Analysis of Behavior: 1983-1992.
AB  - We examined self- and cross-citation practices in JABA and JEAB from 1983 through
      1992. Mean levels of self-citation for JABA and for JEAB were 22.6% and 36.1%,
      respectively. Overall, 2.4% of JABA citations were JEAB articles, and 0.6% of
      JEAB citations were JABA articles, which suggests limited integration of basic
      and applied research.

PMID- 16795847
TI  - Using extinction to promote response variability in toy play.
AB  - We report the effects of extinction and positive reinforcement on the number of
      untrained topographies emitted by children with toys. Baseline showed no
      appropriate toy play. Participants were then trained individually on one
      topography for each toy. Previously reinforced topographies of toy play were
      placed on extinction, resulting in the induction of untrained topographies.

PMID- 16795848
TI  - Replication of a high-probability request sequence with varied interprompt times
      in a preschool setting.
AB  - An intervention for noncompliance consisting of a series of requests promoting a
      high probability of compliance followed either 5 s or 20 s later by a request
      with a low probability of compliance was implemented with a preschool child with
      autism. Results indicated that applications of the request sequence with a
      shorter interprompt time resulted in higher rates of compliance, and longer
      interprompt times resulted in near-baseline rates of compliance.

PMID- 16795850
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      November 1993.

PMID- 16795849
TI  - Shaping in the 21st century: Moving percentile schedules into applied settings.
AB  - The present paper provides a primer on percentile reinforcement schedules, which
      have been used for two decades to study response differentiation and shaping in
      the laboratory. Arranged in applied settings, percentile procedures could be used
      to specify response criteria, standardizing treatment across subjects, trainers,
      and times to provide a more consistent training environment while maintaining the
      sensitivity to the individual's repertoire that is the hallmark of shaping.
      Percentile schedules are also valuable tools in analyzing the variables of which
      responding is a function, both inside and outside the laboratory. Finally, by
      formalizing the rules of shaping, percentile schedules provide a useful heuristic
      of the processes involved in shaping behavior, even for those situations that may
      not easily permit their implementation. As such, they may help further sensitize
      trainers and researchers alike to variables of critical importance in behavior
      change.

PMID- 16795852
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      March 1994.

PMID- 16795851
TI  - Deriving relations from the experimental analysis of behavior.

PMID- 16795853
TI  - Increased sales and thefts of candy as a function of sales promotion activities:
      Preliminary findings.
AB  - We used an A-B-A design to evaluate the effects of two commonly used promotional
      activities-price reduction and increased exposure, in combination and separately
      on sales and thefts of candy at a grocery store. The combination of activities
      and the increased exposure condition produced the greatest increases in sales.
      The combination of activities was also associated with the greatest increase in
      thefts.

PMID- 16795854
TI  - Increasing designated driving with a program of prompts and incentives.
AB  - Designated driving (DD) is a potentially viable but underutilized component of
      efforts to reduce driving while intoxicated. A reversal design was used to
      evaluate the effects of prompts and incentives in a bar on the frequency of DD.
      The results showed an approximate doubling of the number of designated drivers
      during the two intervention periods.

PMID- 16795855
TI  - A comparison of pacing contingencies in classes using a personalized system of
      instruction.
AB  - This study compared the effects of multiple versus single deadline contingencies
      on distribution of unit-mastery test taking by students in four university
      classes taught using the personalized system of instruction. Rate of test taking
      was most uniform when multiple deadlines were imposed throughout the course. When
      deadlines were infrequent, a scalloped pattern of test taking developed.

PMID- 16795856
TI  - The effects of advance notice of activity transitions on stereotypic behavior.
AB  - Using an A-B-A-B design, two procedures for requesting a change of activity were
      compared for their effect on the stereotypic behavior of a man with autism. One
      procedure requested immediate change of activities, whereas the second procedure
      gave advance notice of a change. Less stereotypy occurred when advance notice of
      change was given.

PMID- 16795857
TI  - Prevalence of the extinction burst and its attenuation during treatment.
AB  - Although extinction has been an effective treatment for a variety of behavior
      disorders, its use may be associated with several adverse side effects, the most
      common being an initial increase in the frequency of the target response, called
      an "extinction burst." We attempted to determine the prevalence of the extinction
      burst in applied research and its possible attenuation with other operant
      procedures. An analysis of 113 sets of extinction data indicated that bursting
      may not be as common as previously assumed (it occurred in 24% of the cases) and
      may be less likely when extinction is implemented with alternative procedures
      rather than as the sole intervention (bursting was evident in 12% of the former
      cases and 36% of the latter).

PMID- 16795858
TI  - Comparing choice and questionnaire measures of the acceptability of a staff
      training procedure.
AB  - We compared questionnaire and choice measures of acceptability while evaluating
      effects of staff familiarity versus unfamiliarity with the system used to monitor
      performance during a training program. Staff members rated both monitoring
      formats equally favorably on the questionnaire, whereas when given a choice, they
      frequently chose the familiar format and never chose the unfamiliar format. These
      results suggest that traditional questionnaire evaluations may not be
      sufficiently sensitive measures of acceptability relative to choice measures.

PMID- 16795859
TI  - Comparing interspersed requests and social comments as antecedents for increasing
      student compliance.
AB  - Two students were alternately presented with interspersed high-compliance
      requests and social comments as antecedents to low-compliance requests. An
      initial comparison demonstrated similar positive effects on compliance for
      interspersed requests and social comments. A second analysis indicated that the
      effectiveness of social comments for increasing compliance was related to the
      time interval between social comments and low-compliance requests.

PMID- 16795861
TI  - Wagering on a large scale: Relationships between public gambling and game
      manipulations in two state lotteries.
AB  - Public wagering was examined in relation to game adjustments during the first 523
      draws of Oregon's "Megabucks" lottery and the first 540 draws of Arizona's "The
      Pick" lottery. Oregon's lottery was modified five times during this period, and
      Arizona's lottery underwent four modifications. Public wagering was not related
      to decreases in the odds of winning in either state. Wagering increased in both
      states following the introduction of a minimum $1 million jackpot. Wagering also
      increased following a change in game frequency from weekly to semiweekly draws.
      Sales trends in both states suggest that over the period examined, larger
      jackpots were required to maintain previous levels of lottery play. These data
      suggest that public participation in gambling can be manipulated by state lottery
      commissions through adjustments in lottery contingencies.

PMID- 16795860
TI  - Stimulus equivalence instruction of fraction-decimal relations.
AB  - Stimulus control technology was applied to the instruction of fraction ratio
      (e.g., (1/5)) and decimal (e.g., 0.20) relations, with 7 students who
      demonstrated difficulty in fraction and decimal tasks. The students were trained
      to match pictorial representations of fractions (B comparison stimuli) to printed
      counterpart fraction ratios (A sample stimuli), and to match printed decimals (C
      comparison stimuli) to pictorial representations of counterpart quantities (B
      sample stimuli). Posttest performance by all participants indicated the emergence
      of equivalence relations between fractions represented as ratios, decimals, and
      pictures. Limited generalization of fraction-decimal relations was observed.

PMID- 16795862
TI  - Effect of response practice variables on learning spelling and sight vocabulary.
AB  - Four experiments were conducted to examine variables associated with response
      practice as an instructional technique for individuals with intellectual
      disabilities. In Experiment 1, the effect of the cover component in the "cover
      write" method was evaluated, as were the comparative effects of written versus
      oral practice of spelling words by rehabilitation clients. The results showed
      that the cover procedure generally did not enhance performance over and above
      that produced by practice alone, and written practice generally was not superior
      to oral practice. Experiment 2 demonstrated that less response practice (i.e.,
      five times) was as effective as more practice (i.e., 10 and 15 times) for
      teaching spelling to adolescents with developmental disabilities. Experiments 3
      and 4 also showed that even less response practice (i.e., one time) was as
      effective as more practice (five times), and irrelevant practice following errors
      was as effective as relevant practice for teaching spelling and sight vocabulary
      to adolescents with behavior disorders and developmental disabilities,
      respectively. The findings suggest that a parsimonious procedure of limited
      response practice and positive reinforcement may be effective for the tasks and
      populations studied.

PMID- 16795863
TI  - The effects of multiple-exemplar self-instructional training on high school
      students' generalized conversational interactions.
AB  - A multiple-baseline-across-students design was used to investigate the effects of
      multiple-exemplar self-instructional training on the acquisition and
      generalization of conversational interaction of 4 high school students with
      mental retardation. The multiple-exemplar component of the model consisted of (a)
      several peers without disabilities teaching the use of a self-instructional
      social skills strategy across diverse examples of conversational interactions and
      across two settings and (b) assessing the generalized effects of training across
      additional peers and one setting. Findings indicated that peers were effective in
      teaching the multiple-exemplar strategy and that peer training was associated
      with systematic increases in generalized conversational interactions with
      familiar and unfamiliar peers with and without disabilities in an additional
      setting. Social validation data indicated that following multiple-exemplar
      training, all participants' performances approximated those of general education
      students and was judged by others to have improved.

PMID- 16795865
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior, May
      1994.

PMID- 16795864
TI  - Effects of differential negative reinforcement on disruption and compliance.
AB  - We examined the effects on compliance of two types of differential negative
      reinforcement (DNR) with a 5-year-old girl with a history of severe disruption.
      During DNR (communication), escape from instructional trials was provided
      contingent on a communicative behavior. During DNR (compliance), escape was
      provided contingent on compliance. Both interventions decreased inappropriate
      behavior and increased appropriate behavior. However, during DNR (communication),
      compliance rarely occurred.

PMID- 16795867
TI  - Research on training trainers in program implementation: An introduction and
      future directions.

PMID- 16795866
TI  - The applied importance of research on the matching law.
AB  - In this essay, we evaluate the applied implications of two articles related to
      the matching law and published in the Journal of the Experimental Analysis of
      Behavior, May 1994. Building on Mace's (1994) criteria for increasing the applied
      relevance of basic research, we evaluate the applied implications of basic
      research studies. Research by Elsmore and McBride (1994) and Savastano and
      Fantino (1994) involve an extension of the behavioral model of choice. Elsmore
      and McBride used rats as subjects, but arranged a multioperant environment that
      resembles some of the complex contingencies of human behavior. Savastino and
      Fantino used human subjects and extended the matching law to ratio and interval
      contingencies. These experiments contribute to a growing body of knowledge on the
      matching law and its relevance for human behavior.

PMID- 16795869
TI  - Selected abstracts from the Journal of the Experimental Analysis of Behavior,
      November 1994.

PMID- 16795868
TI  - Isolating the effects of active responding in computer-based instruction.
AB  - This experiment evaluated the effects of requiring overt answer construction in
      computer-based programmed instruction using an alternating treatments design.
      Four college students worked through an instructional program that alternated
      between presenting frames with blanks requiring overt responses and complete
      frames without blanks. All students produced a higher percentage of correct
      posttest answers corresponding to program segments that required overt answer
      construction.

PMID- 16795870
TI  - The paradox of preference for unreliable reinforcement: The role of context and
      conditioned reinforcement.
AB  - We discuss Belke and Spetch's (1994) work on choice between reliable and
      unreliable reinforcement. The studies by Belke and Spetch extend a line of basic
      research demonstrating that under certain experimental conditions in a concurrent
      chains procedure, pigeons prefer an alternative that produces unreliable
      reinforcement. The authors describe the variables that influence preference for
      unreliable reinforcement, including the signaling and the duration of the
      reinforcement schedules, the context in which the signaling stimuli occur, and
      the effects of conditioned reinforcement. Hypothetical applied examples that
      address these variables are provided, and their influence on preference for
      unreliable reinforcement in humans is discussed. We conclude by suggesting a line
      of applied research to examine the relationship between these variables and a
      preference for unreliable reinforcement.

PMID- 16795871
TI  - Current societal concerns: Introduction.

PMID- 16795872
TI  - The effects of a sportsmanship curriculum intervention on generalized positive
      social behavior of urban elementary school students.
AB  - This study evaluated the effects of an elementary physical education curriculum
      in which development of positive social skills, including leadership and conflict
      resolution behaviors, was the primary focus. A second goal was to determine
      possible generalization effects beyond the primary intervention setting. Students
      in two urban elementary physical education classes served as subjects, with a
      third class used as a comparison. The effects of the curriculum intervention were
      evaluated in the training setting and in the students' regular education
      classrooms using a multiple baseline across classrooms design. Results showed (a)
      an immediate increase in student leadership and independent conflict-resolution
      behaviors, (b) an increase in percentage of class time devoted to activity
      participation, and (c) decreases in the frequency of student off-task behavior
      and percentage of class time that students devoted to organizational tasks.
      Similar changes in student behavior were also observed in the regular classroom
      settings.

PMID- 16795873
TI  - Child abuse and neglect by parents with disabilities: A tale of two families.
AB  - Two families, in which the children had been placed in foster care due to abuse
      and neglect by parents who had disabilities, were studied. In the first case, the
      mother was instructed in skills that our assessment suggested were important for
      her child's survival. The mother readily acquired and applied these skills, a
      fact reflected both in changes in her behavior and in changes in the child's well
      being. In the second case, the parent's incremental resumption of child custody
      was made contingent upon completion of relevant parenting tasks. Initially,
      improvements in the completion of such tasks were evident, but over time and with
      the onset of militating factors, no further progress was made and all parental
      rights were terminated. The implications of these cases for behavior analysis and
      the effort to reunite and preserve families are discussed.

PMID- 16795874
TI  - Direct assessment of quality of care in a geriatric nursing home.
AB  - Direct observation was used to examine multiple aspects of care provided in a
      proprietary nursing home. The samples were taken at random intervals, 7 days per
      week for 5 weeks, across several categories of environmental and resident
      conditions as well as staff and resident activity. Results showed a high degee of
      compliance with predefined standards (based on current federal regulations) for
      environmental and resident conditions. Overall distributions of resident and
      staff activity showed results similar to those found in previous studies, with
      residents spending most of their time engaged in nonsocial activity and staff
      spending the majority of their time engaged in nonresident work. When data were
      analyzed across areas of the facility, times of day, and weekdays versus
      weekends, some differences were noted. Weekend versus weekday comparisons showed
      higher resident:staff ratios on weekends and more resident inactivity, but no
      significant differences in environmental or resident conditions. In addition,
      more frequent resident care, resident interaction, and resident activity were
      observed in Medicare units than in non-Medicare units. Results are discussed in
      terms of federal requirements for monitoring the quality of care in nursing homes
      and the potential use of time sampling expressly for this purpose.

PMID- 16795875
TI  - Using public feedback to increase contributions to a multipurpose senior center.
AB  - Multipurpose senior centers are expanding their services to meet the demands of a
      growing population. Unfortunately, federal agencies have not matched this
      expansion with monetary support. Many senior centers hold fund-raisers to
      supplement their budgets, but the impact of these projects is rarely evaluated.
      This study assessed the effectiveness of a public posting strategy designed to
      increase donations to an ongoing fund-raiser for a multipurpose senior center.
      The fund-raiser, "Coupons for Caring," consisted of senior volunteers clipping
      grocery coupons from newspapers, sorting them, and attaching them to their
      respective products in local grocery stores. Grocery store customers were given
      the option of donating the coupons to the senior center or redeeming them when
      they purchased the products to which the coupons were attached. In the
      experimental condition, signs were posted that included visual and written
      instructions, feedback on the value of coupons donated by customers the previous
      week, and feedback on the overall amount of money donated to the senior center.
      The signs were posted near each cashier stand and at the front entrances of the
      grocery stores in a multiple baseline across grocery stores. The percentage of
      coupons donated to the senior center increased at each store after the signs were
      posted.

PMID- 16795876
TI  - Effect of dispenser location on taking free condoms in an outpatient cocaine
      abuse treatment clinic.
AB  - Crack cocaine use increases risky sexual behavior and HIV exposure; therefore,
      safe sexual practices should be encouraged during cocaine addiction treatment.
      Research indicates that placing condom dispensers in private restrooms increases
      taking free condoms. We investigated two other dispenser locations (a day room
      vs. counselors' offices) and found that substantially more condoms were taken
      when dispensers were in the day room. This is an important issue for public
      health facilities without private restrooms.

PMID- 16795877
TI  - Preventing antisocial behavior in the schools.
AB  - Multiple correlates and determinants of antisocial behavior within the home,
      community, and school are reviewed. Due to the school's pivotal role in our
      society, an emphasis is placed on how our schools contribute to antisocial
      behavior, and what educators can do to prevent anti-social behavior and related
      attendance problems. A variety of contextual factors and setting events within
      our schools appear to be major contributors to antisocial behavior, and some of
      the same factors identified within the schools also have been identified within
      the home. These setting events, rather than quick restrictive fixes, must be
      given more attention if we are to provide safe school environments-environments
      that durably prevent antisocial behavior and related attendance problems.

PMID- 16795878
TI  - Eliminating the battering of women by men: Some considerations for behavior
      analysis.
AB  - Based on review of representative literature, history and current research
      indicate that battering by male partners is a major health problem for women. Use
      of physical aggression and verbal coercion can be described by three-term
      contingencies involving escape, avoidance, punishment, and positive
      reinforcement. These contingencies occur within societal practices, rules, and
      models that involve oppression of women and insubstantial consequences for men
      who batter. The difficulties in directly observing a couple's interactions and
      their aggression have been a methodological barrier to the involvement of
      behavior analysts in treatment of and research on domestic violence.
      Recommendations are made for behavior analysts to contribute to reducing
      battering through development and analysis of program components and application
      of contingency management and behavioral training technology.

PMID- 16795879
TI  - On advancing behavior analysis in the treatment and prevention of battering:
      Commentary on Myers.
AB  - MYERS OFFERS AN IMPORTANT CHALLENGE TO BEHAVIOR ANALYSTS: eliminating the
      battering of women. In this commentary, we extend the conceptual model advocated
      by Myers, urge a bidirectional approach that focuses more on the battered woman
      and less on the battering man, caution against the indiscriminate use of marital
      therapy approaches, and argue that the most important contributions in the field
      may come from behavioral prevention rather than treatment interventions.

PMID- 16795880
TI  - Analysis of establishing operations for self-injury maintained by escape.
AB  - Self-injurious behavior (SIB) can be maintained through negative reinforcement
      when, in the context of training or task requirements, it produces escape as a
      consequence. Several studies have demonstrated methods for identifying and
      treating SIB maintained by negative reinforcement; however, few analyses of the
      establishing operations associated with demand situations have been conducted.
      The current series of studies illustrates a method for identifying some
      establishing operations for escape by systematically altering certain dimensions
      of the demand context while maintaining an escape contingency for SIB. Dimensions
      assessed in these studies included task novelty, duration of instructional
      sessions, and rate of task presentation. Data indicate that these variables can
      have establishing properties for behavior maintained by escape. Implications of
      the results are discussed, as are potential refinements and extensions of the
      assessment procedures.

PMID- 16795881
TI  - Identification and modification of a response-class hierarchy.
AB  - We evaluated the effects of extinction and negative reinforcement on the latency
      of response-class members following requests made to a 15-year-old female with
      moderate mental retardation and autism. A functional analysis showed that the
      class members (screams, aggression, and self-injury) were escape maintained.
      Informal observations suggested that these topographies generally occurred in the
      sequence listed above and therefore may have been hierarchically related. A
      therapist provided escape from demands contingent on a specific member of the
      class to determine the effects on the latency of the members' occurrence. Results
      showed that the latencies occurred in a predictable order. In addition, we
      expanded the response class to include a vocal response that was functionally
      equivalent to other members. Findings are discussed regarding the covariation and
      sequence of response-class members and treatment development.

PMID- 16795883
TI  - The relationship between pronunciation and listening discrimination when Japanese
      natives are learning English.
AB  - Two Japanese students were taught to pronounce and discriminate English words
      that contain unfamiliar phonemic contrasts (e.g., rock and lock). Teaching
      pronunciation was found to be easier than teaching listening discrimination.
      Teaching listening discrimination resulted in collateral improvement in
      pronunciation and, to a lesser extent, vice versa.

PMID- 16795882
TI  - Progressing from brief assessments to extended experimental analyses in the
      evaluation of aberrant behavior.
AB  - The role of experimental analyses in guiding treatment is well established.
      However, not all experimental analyses yield conclusive results. Outcomes may be
      inconclusive due to time limitations that preclude extended observation and
      detailed experimental manipulations, or may result from interactions across
      experimental conditions, multiple control, or other unknown factors. In this
      study, we describe an assessment sequence that moves through four phases
      beginning with relatively brief (1 to 2 hr) analyses and culminating in extended
      analyses that may control for experimental confounding effects (e.g., interaction
      effects). Data illustrating the model are presented for 20 individuals referred
      for severe behavior problems including self-injury, aggression, stereotypy, and
      tantrums. Analyses were considered to be complete only when clear and replicable
      response patterns emerged. Results showed that clear and replicable response
      patterns emerged for 85% of the participants.

PMID- 16795884
TI  - Preliminary comparison of two negative reinforcement schedules to reduce self
      injury.
AB  - This study compared the effectiveness of differential negative reinforcement of
      other behavior (DNRO) and alternative behavior (DNRA) for reducing self-injurious
      tantrums maintained by escape from demands in a 4-year-old girl with severe
      retardation. Both DNRA and DNRO reduced self-injury and increased independent
      performance of two tasks (tooth brushing and bathing); however, improvement on
      both measures was greater with the DNRA intervention.

PMID- 16795885
TI  - Selected abstract from the Journal of the Experimental Analysis of Behavior, May
      1995.

PMID- 16795886
TI  - Making life easier with effort: Basic findings and applied research on response
      effort.
AB  - Early basic research showed that increases in required response effort (or force)
      produced effects that resembled those produced by punishment. A recent study by
      Alling and Poling determined some subtle differences between the two behavior
      change strategies, but also confirmed that increasing required effort is an
      effective response-reduction procedure with enduring effects. In this paper we
      summarize basic research on response effort and explore the role of effort in
      diverse applied areas including deceleration of aberrant behavior, attention
      deficit hyperactivity disorder, oral habits, health care appointment keeping,
      littering, indexes of functional disability, and problem solving. We conclude
      that renewed interest in response effort as an independent variable is justified
      because of its potent effects and because the political constraints imposed on
      punishment- and reinforcement-based procedures have yet to be imposed on
      procedures that entail manipulations of response effort.

PMID- 16795887
TI  - Group versus individual reinforcement contingencies within the context of group
      study conditions.
AB  - We investigated the effects of two teaching variables on students' Spanish
      vocabulary quiz performance: (a) group study and (b) individual versus group
      contingencies. In Experiment 1, we compared students' quiz scores under
      conditions in which students either studied independently and received no
      programmed reinforcement or studied in groups and received individual rewards for
      high scores. The results showed that, on average, the group-study individual
      reward condition produced superior quiz scores. In Experiment 2, we compared
      individual (i.e., the superior condition in Experiment 1) and group contingencies
      within the context of the group study condition. On average across the class,
      group contingencies produced performance superior to individual contingencies. In
      both studies, however, benefits for the classes as a whole were mitigated by
      effects on individual students. These results extend the literature on the
      effects of group-based instructional activities and reinforcement contingencies.
      Educators who choose such procedures may encounter conflicting findings depending
      on whether they examine results at the group or individual level.

PMID- 16795889
TI  - Comments on lerman and iwata (1996).

PMID- 16795888
TI  - Recent reinforcement-schedule research and applied behavior analysis.
AB  - Reinforcement schedules are considered in relation to applied behavior analysis
      by examining several recent laboratory experiments with humans and other animals.
      The experiments are drawn from three areas of contemporary schedule research:
      behavioral history effects on schedule performance, the role of instructions in
      schedule performance of humans, and dynamic schedules of reinforcement. All of
      the experiments are discussed in relation to the role of behavioral history in
      current schedule performance. The paper concludes by extracting from the
      experiments some more general issues concerning reinforcement schedules in
      applied research and practice.

PMID- 16795890
TI  - Selected abstracts from the journal of the experimental analysis of behavior,
      july 1992 and january 1996.

PMID- 16795891
TI  - Editorial.

PMID- 16795892
TI  - Teaching reading and spelling: exclusion and stimulus equivalence.

PMID- 16795893
TI  - APA Awards: Divisions 16 And 25.

PMID- 16795894
TI  - The momentum of compliance.

PMID- 16795895
TI  - Compliant in a moment: a commentary on nevin.

PMID- 16795897
TI  - Responding To Requests For Reprints: How Do JABA Authors Meassure Up?

PMID- 16795898
TI  - Bringing together video technology, research, and practice: a review of practical
      guide to using video in the beavioral sciences by dowrick and associates.

PMID- 16795896
TI  - Internet resources in applied behavior analysis.

PMID- 16795899
TI  - Make no bones about it, calcium supplements still count.

PMID- 16795900
TI  - Gout's not just for the gluttonous.

PMID- 16795902
TI  - Coping well with leaving the hospital.

PMID- 16795901
TI  - Parkinson's goal: ease symptoms, slow progression.

PMID- 16795903
TI  - Is your stomach depressed?

PMID- 16795904
TI  - How can I lower my triglycerides?

PMID- 16795905
TI  - Kidney tests. A crucial part of diabetes care.

PMID- 16795906
TI  - Midyear resolution. Eating tips for a healthier you.

PMID- 16795907
TI  - A great invention. The implantable cardioverter defibrillator.

PMID- 16795908
TI  - Coming down the pipeline. The race is on to bring you more treatment options for
      type 2 diabetes than ever before.

PMID- 16795910
TI  - A shrinking stomach. What you need to know about stomach surgery for weight loss.

PMID- 16795909
TI  - Reading, writing & winnowing wheat.
AB  - Thanks to world-renowned chef Alice Waters, the kids in one California school
      went from eating fast-food lunches on a crumbling blacktop to growing and
      preparing their own fresh-food feasts. Could this idea help stave off a national
      obesity epidemic?

PMID- 16795911
TI  - The dawn phenomenon. One reason for morning highs.

PMID- 16795912
TI  - Good news for nerves. A landmark diabetes study has already found that tight
      control pays off for your eyes, heart, and kidneys. Now, the spotlight is on
      nerves.

PMID- 16795913
TI  - Sweets for summer. These cool fruit desserts take the heat off.

PMID- 16795914
TI  - Research profile. Dangerous snoozing. Surgery, sleep apnea, and diabetes. Denham
      S. Ward, MD, PhD.

PMID- 16795915
TI  - Debating global HIV incidence.

PMID- 16795916
TI  - CDC to urge routine HIV tests for a broad swath of Americans.

PMID- 16795917
TI  - Can drugs prevent HIV infection?

PMID- 16795918
TI  - Tribulations and trials in HIV disease, Part 2.

PMID- 16795919
TI  - Images in HIV/AIDS. HIV-associated squamous cell carcinoma of the anus.

PMID- 16795920
TI  - Progressive multifocal leukoencephalopathy in the era of highly active
      antiretroviral therapy.

PMID- 16795921
TI  - Management of hepatitis C virus coinfection in HIV-infected persons.
AB  - Approximately 300,000 patients in the United States are coinfected with HIV and
      hepatitis C virus (HCV). More rapid progression of HCV-related liver disease is
      seen in coinfected patients than in HCV-monoinfected patients. Since the
      introduction of potent antiretroviral therapy, liver disease has become a leading
      cause of death in HIV-infected patients. Therefore, more aggressive management of
      HCV-related liver disease is essential in HIV-positive patients. Recently,
      several trials have established the superiority of pegylated interferon alfa in
      combination with ribavirin to standard interferon with ribavirin for treatment of
      HCV infection in HIV-HCV-coinfected patients. Sustained virologic response (SVR)
      rates were only 14% to 29% in genotype 1 and 43% to 73% in genotype 2 and 3 HCV
      with 48 weeks of combination therapy. Absence of an early virologic response
      determined at 12 weeks can limit treatment exposure in patients destined not to
      achieve an SVR. The risk of interactions between drugs used to treat hepatitis C
      and those for HIV, such as between ribavirin and didanosine, needs to be
      considered before initiating treatment in HIV-HCV-coinfected patients.

PMID- 16795922
TI  - Determining a one-tailed upper limit for future sample relative reproducibility
      standard deviations.
AB  - A formula was developed to determine a one-tailed 100p% upper limit for future
      sample percent relative reproducibility standard deviations (RSD(R),%=
      100s(R)/y), where S(R) is the sample reproducibility standard deviation, which is
      the square root of a linear combination of the sample repeatability variance
      (s(r)2) plus the sample laboratory-to-laboratory variance (s(L)2), i.e., S(R) =
      s(L)2, and y is the sample mean. The future RSD(R),% is expected to arise from a
      population of potential RSD(R),% values whose true mean is zeta(R),% = 100sigmaR,
      where sigmaR and mu are the population reproducibility standard deviation and
      mean, respectively.

PMID- 16795923
TI  - Improving the biocompatibility of in vivo sensors via nitric oxide release.
AB  - The continuous, real-time monitoring of clinically important analytes (e.g., PO2,
      PCO2, pH, K+, Na+, glucose, and lactate) is of great importance to human health
      care. Despite considerable efforts spanning several decades, the use of in vivo
      sensors clinically remains limited due to inadequate biocompatibility. The
      discovery of nitric oxide (NO) as an effective inhibitor of platelet and
      bacterial adhesion has opened a new direction of research related to designing
      the next generation of in vivo sensors. In this Highlight article, recent
      progress in designing more biocompatible in vivo sensors is described, with a
      particular focus on preparing interfaces that resist biofouling via controlled NO
      release.

PMID- 16795924
TI  - Outbreak news. Malaria, Bahamas.

PMID- 16795925
TI  - Progress towards polio eradication in Afghanistan and Pakistan, January 2005 to
      May 2006.

PMID- 16795926
TI  - Bibliography. Current World Literature. Headache.

PMID- 16795927
TI  - Office of the Secretary; TRICARE; changes included in the National Defense
      Authorization Act for fiscal year 2005; TRICARE dental program. Final rule.
AB  - The Department is publishing this final rule to implement sections 711 and 715 of
      the Ronald W. Reagan National Defense Authorization Act for Fiscal Year 2005
      (NDAA for FY05), Public Law 108-375. Specifically, that legislation makes young
      dependents of deceased Service members eligible for enrollment in the TRICARE
      Dental program when the child was not previously enrolled because of age, and
      authorizes post-graduate dental residents in a dental treatment facility of the
      uniformed services under a graduate dental education program accredited by the
      American Dental Association to provide dental treatment to dependents who are 12
      years of age or younger and who are covered by a dental plan established under 10
      U.S.C. 1076a. This adopts the interim rule published on September 21, 2005 (70 FR
      55251).

PMID- 16795929
TI  - What is this chromatographic behavior called "phase collapse"?

PMID- 16795928
TI  - What is causing the different sensitivities in my GCs?

PMID- 16795930
TI  - Office of the Secretary; Civilian Health and Medical Program of the Uniformed
      Services (CHAMPUS); transitional assistance management program; early eligibility
      for TRICARE for certain reserve component members. Final rule.
AB  - This final rule revises requirements and procedures for the Transitional
      Assistance Management Program, which was temporarily revised by section 704 of
      the National Defense Authorization Act for Fiscal Year 2004 (NDAA-04) (Pub. L.
      108-136) and section 1117 of the Emergency Supplemental Appropriations Act for
      the Reconstruction of Iraq and Afghanistan, 2004 (Emergency Supplemental) (Pub.
      L. 108-106), which revisions were made permanent by section 706(a) of the Ronald
      W. Reagan National Defense Authorization Act for Fiscal Year 2005 (NDAA-05) (Pub.
      L. 108-375). In addition, it establishes requirements and procedures for
      implementation of the earlier TRICARE eligibility for certain reserve component
      members authorized by section 703 of NDAA-04 and section 1116 of the Emergency
      Supplemental, which provisions were made permanent by section 703 of NDAA-05. The
      rule adopts the interim rule published in the Federal Register on March 16, 2005
      (70 FR 12798).

PMID- 16795931
TI  - One dendritic arbor, two modes of integration.

PMID- 16795932
TI  - Mirror neurons and the lateralization of human language.

PMID- 16795933
TI  - International Conference on Harmonisation; guidance on Q9 Quality Risk
      Management; availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "Q9 Quality Risk Management."' The guidance was prepared under
      the auspices of the International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH). The
      guidance provides principles and examples of tools for quality risk management
      that can be applied to all aspects of pharmaceutical quality throughout the
      lifecycle of drug substances, drug products, and biological and biotechnological
      products. The guidance is intended to enable regulators and industry to make more
      effective and consistent risk-based decisions.

PMID- 16795934
TI  - Medical devices; exception from general requirements for informed consent.
      Interim final rule.
AB  - The Food and Drug Administration (FDA) is issuing this interim final rule to
      amend its regulations to establish a new exception from the general requirements
      for informed consent, to permit the use of investigational in vitro diagnostic
      devices to identify chemical, biological, radiological, or nuclear agents without
      informed consent in certain circumstances. The agency is taking this action
      because it is concerned that, during a potential terrorism event or other
      potential public health emergency, delaying the testing of specimens to obtain
      informed consent may threaten the life of the subject. In many instances, there
      may also be others who have been exposed to, or who may be at risk of exposure
      to, a dangerous chemical, biological, radiological, or nuclear agent, thus
      necessitating identification of the agent as soon as possible. FDA is creating
      this exception to help ensure that individuals who may have been exposed to a
      chemical, biological, radiological, or nuclear agent are able to benefit from the
      timely use of the most appropriate diagnostic devices, including those that are
      investigational.

PMID- 16795935
TI  - Medical devices; ear, nose, and throat devices; classification of olfactory test
      device. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the olfactory test device
      into class II (special controls). The special control that will apply to the
      device is the guidance document entitled "Class II Special Controls Guidance
      Document: Olfactory Test Device." The agency is classifying the device into class
      II (special controls) in order to provide a reasonable assurance of safety and
      effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA
      is announcing the availability of the guidance document that is the special
      control for the device.

PMID- 16795937
TI  - Splint equal to cast for wrist buckle fracture in children.

PMID- 16795936
TI  - Physician, heal thyself: Rx for mental health.

PMID- 16795939
TI  - Guideline: Hip dysplasia screening has insufficient evidence.

PMID- 16795938
TI  - Management of antiphospholipid antibody syndrome.

PMID- 16795941
TI  - Antidepressant drugs increase suicide risk in children.

PMID- 16795940
TI  - 100% humidity no better than blow-by for croup.

PMID- 16795942
TI  - Lower respiratory tract infections: treating patients or diagnoses?

PMID- 16795943
TI  - Prescription Drug Marketing Act Pedigree Requirements; effective date and
      compliance policy guide; request for comment. Final rule; announcement of
      effective date; notice of availability; request for comment.
AB  - The Food and Drug Administration (FDA) does not intend to further delay the
      effective date of certain provisions of the final regulation published in the
      Federal Register of December 3, 1999 (64 FR 67720). The provisions will therefore
      go into effect on December 1, 2006. In addition, FDA is announcing the
      availability of a new compliance policy guide (CPG) 160.900 entitled
      "Prescription Drug Marketing Act Pedigree Requirements Under 21 CFR Part 203" for
      public comment. This CPG describes how the agency intends to prioritize its
      enforcement efforts during the next year with respect to pedigree requirements
      set forth in the Federal Food, Drug, and Cosmetic Act (the act) and certain FDA
      regulations.

PMID- 16795944
TI  - 2006 resolutions range from welfare philosophy to finances: seven measures to be
      deliberated by House of Delegates.

PMID- 16795946
TI  - AVMA answers: Dr. Beaver reflects. (Interview by Allison Rezendes).

PMID- 16795947
TI  - AVMA GHILT continues commitment to wellness. Veterinarians attending AVMA
      convention will participate in first national occupational risk survey for
      Leptosira.

PMID- 16795948
TI  - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/ TRICARE;
      coverage of phase II and phase III clinical trials sponsored by the National
      Institutes of Health National Cancer Institute. Final rule.
AB  - The final rule allows the Department of Defense to waive normal requirements so
      that covered beneficiaries can participate in Phase II and Phase III clinical
      trials sponsored or approved by the National Institutes of Health National Cancer
      Institute (NIH NCI). This waiver authority is expected to promote beneficiary
      access to promising new treatments and contribute to the development of such
      treatments.

PMID- 16795949
TI  - Heifer International hosts veterinary tour of tsunami recovery in India:
      participants also learn about local culture, values in villages of Tamil Nadu.

PMID- 16795950
TI  - Watchung for signs, symptoms of disease: syndromic surveillance might be a method
      for detecting outbreaks sooner.

PMID- 16795951
TI  - Research, educational center promotes animal coproducts.

PMID- 16795952
TI  - Medicare program; identification of backward compatible version of adopted
      standard for e-prescribing and the Medicare prescription drug program (version
      8.1). Interim final rule with comment period.
AB  - This interim final rule with comment period identifies the Prescriber/Pharmacist
      Interface SCRIPT Standard, Implementation Guide, Version 8.1 (hereafter referred
      to as "Version 8.1 of the National Council for Prescription Drug Programs (NCPDP)
      SCRIPT Standard") as a backward compatible update of the adopted Version 5.0.
      This interim final rule with comment period also permits the voluntary use of
      Version 8.1 of the NCPDP SCRIPT Standard for conducting certain e-prescribing
      transactions for the electronic prescription drug program under Title I of the
      Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA).

PMID- 16795953
TI  - Oral pathology quiz #35. Case number 2. Necrotizing sialometaplasia.

PMID- 16795954
TI  - Oral pathology quiz #45. Case number 2. Lipoma.

PMID- 16795955
TI  - Oral pathology quiz #48. Case number 2. Focal epithelial hyperplasia.

PMID- 16795956
TI  - Oral pathology quiz #48. Case number 4. Botryoid odontogenic cyst.

PMID- 16795957
TI  - Oral pathology quiz #43. Case number 2. Ameloblastoma.

PMID- 16795958
TI  - Oral pathology quiz #43. Case number 4. Squamous cell papilloma.

PMID- 16795959
TI  - Oliver St John Gogarty, MD (1878-1957).

PMID- 16795960
TI  - The Indian Medical Service.

PMID- 16795961
TI  - Laparoscopic cholecystectomy has become the new gold standard for the management
      of symptomatic gallbladder stones.

PMID- 16795962
TI  - Extended lymph node dissection in gastric carcinoma: should we change our policy
      after the long-term results of dutch randomized trial?

PMID- 16795963
TI  - Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients
      with ulcerative colitis--results of a field study.
AB  - BACKGROUND/AIMS: In the treatment of ulcerative colitis, 5-aminosalicylic acid is
      the standard therapy for both acute exacerbations of the disease and the
      maintenance of remission. Clinical studies have shown that olsalazine (Dipentum)-
      a prodrug converted to two molecules of 5-ASA by colonic bacteria-induces and
      maintains remission. This study aimed to investigate the efficacy and
      tolerability of olsalazine in patients with ulcerative colitis who were being
      treated in daily practice by private physicians specializing in gastroenterology.
      METHODOLOGY: A total of 260 patients with ulcerative colitis (aged 17-77 years,
      116 men) were studied. The doses of olsalazine and the clinical data (including
      acute disease symptoms and the occurrence of adverse events) were recorded over a
      6-month period. RESULTS: Twenty per cent of patients had pancolitis, 48% had left
      sided disease and 32% had proctitis or proctosigmoiditis. At study entry, 86% of
      patients had active disease; the percentages of these patients in remission after
      6 weeks and 6 months were 42% and 91%, respectively. Patients with active disease
      received a mean dose of olsalazine - 2324mg per day initially and 1325mg per day
      at 6 months. The corresponding figures for patients in remission at study entry
      were 1386mg and 1162mg per day, respectively. Seventy-three per cent of patients
      took olsalazine with food, as recommended. The overall rate of adverse events was
      low; no serious adverse events occurred. CONCLUSIONS: Olsalazine therapy resulted
      in a rapid regression in the acute symptoms of ulcerative colitis. Olsalazine was
      also effective in maintaining remission. The drug was well tolerated.

PMID- 16795964
TI  - Resectability of hepatocellular carcinoma: evaluation of 333 consecutive cases at
      a single hepatobiliary specialty center and systematic review of the literature.
AB  - BACKGROUND/AIMS: To determine resectability rates in patients with hepatocellular
      carcinoma (HCC) evaluated for surgical therapy. Liver resection constitutes a
      potentially curative treatment for HCC. However, because of the co-existing
      cirrhosis or the late diagnosis, only a percentage of the patients evaluated can
      undergo surgery. METHODOLOGY: We evaluated 333 patients with HCC admitted to our
      center with the intent to treat by means of tumor resection during a 6-year time
      period. RESULTS: Surgical resection with curative intent was undertaken in 116
      patients (35%). In our series, resectability rates were significantly higher in
      patients with solitary HCCs (p<0.001), unilobar tumor distribution (p=0.03), and
      no cirrhosis (p <0.001). Transarterial chemoembolization (TACE) was the most
      frequent approach for nonresectable cases (18% of patients). A systematic
      literature review was performed in order to estimate resectability rates at other
      hepatobiliary centers offering multimodal treatment approaches to HCC. Results
      showed an overall resectability rate of 30%, with 1808 resections reported in
      6108 cases. Resectability rates were significantly higher in Japanese and Eastern
      series when compared to American and Western studies respectively (p<0.001).
      CONCLUSIONS: Treatment strategies for HCC require a multidisciplinary
      comprehensive approach encompassing surgeons, hepatologists, radiologists, and
      oncologists. Surgical resection was possible in only 35% and 30% of patients with
      HCC evaluated for surgical therapy in our series and in the world literature,
      respectively. TACE was the primary treatment modality for non-resectable cases. A
      "no therapy" option was chosen in 21% of cases worldwide.

PMID- 16795965
TI  - Antegrade biliary stenting versus T-tube drainage after laparoscopic
      choledochotomy--a comparative cohort study.
AB  - BACKGROUND/AIMS: Laparoscopic exploration of the common bile duct (LECBD) has
      been proven to be an effective and preferred treatment approach for uncomplicated
      common bile duct stones. However there is still controversy regarding the choice
      of biliary decompression after laparoscopic choledochotomy. METHODOLOGY: This is
      a retrospective comparison between the use of antegrade biliary stenting and T
      tube drainage following successful laparoscopic choledochotomy. During the period
      between January 1995 and July 2003, biliary decompression was achieved by either
      antegrade biliary stenting or T-tube drainage based on the discretion of the
      operating surgeon. For antegrade biliary stenting, a 10-Fr Cotton-Leung biliary
      stent was inserted through the choledochotomy and passed down across the papilla.
      The stent position was confirmed by on-table choledochoscopy before interrupted
      single-layered closure of the common bile duct. Endoscopic retrograde
      cholangiopancreatography (ERCP) was performed to remove the stent 4 weeks after
      operation and at the same time to check for any residual stones or other
      complications like stricture or leak. In the T-tube group, a 16-Fr latex T-tube
      was used and the long limb was brought out through the subcostal trocar port
      followed by the same method of bile duct closure. Cholangiogram through the T
      tube was performed on day 7 and the tube would be taken off 1 week later (about 2
      weeks after operation) if the cholangiogram did not reveal any abnormality. The
      two groups were compared according to the demographic data, operation time,
      length of hospital stay and complication rates. RESULTS: During the study period,
      108 laparoscopic explorations of the common bile duct were performed in our
      centre of which 95 were attempted laparoscopic choledochotomies and 13 were
      transcystic duct explorations. Of the 95 patients with attempted laparoscopic
      choledochotomy, there were 9 open conversions, 17 laparoscopic bilioenteric
      bypasses and 6 primary closures of the common bile duct. All of these patients
      together with those receiving transcystic duct explorations were excluded and the
      remaining 63 patients having postoperative bile diversion by either antegrade
      biliary stenting or T-tube drainage were included in this study. Bile diversion
      was achieved by antegrade biliary stenting in 35 patients whereas 28 patients had
      T-tube drainage. There was no difference between the two groups in terms of age,
      clinical presentation, bilirubin level, length of hospital stay, follow-up
      duration, common bile duct size, size of common bile duct stones, incidence of
      residual/recurrent stone and complication rate. It was observed that more
      patients in the stenting group developed bile leak (14.2% vs. 3.5%) and required
      more intramuscular pethidine injections (182.86 +/- 139.30 vs. 92.81+/-81.15mg,
      P=0.000). On the other hand, the T-tube group had longer operation time (141.4+/
      45.1 vs. 11 1.1+/-33.9 minutes, P=0.006) and had a longer postoperative hospital
      stay (10.0+/-7.4 vs. 8.8+/-9.3 days, P=0.020) reaching statistical significance.
      CONCLUSIONS: Postoperative bile diversion by antegrade biliary stenting after
      laparoscopic choledochotomy is shown to shorten operation duration and
      postoperative stay as compared to T-tube drainage, but the problem of bile leak
      needs further refinement of insertion technique.

PMID- 16795966
TI  - New concept of cholecystectomy combined resection of the gallbladder bed for
      chronic cholecystitis.
AB  - Cholecystectomy is sometimes the most difficult operation to perform. When the
      atrophic gallbladder with severe inflammation falls into the spongy soft liver,
      it is not easy to perform a standard cholecystectomy without causing bleeding and
      serious injury around the hilar structures. Some selected patients with chronic
      cholecystitis under some particular circumstances might be better suited to
      undergo a cholecystectomy combined resection with the gallbladder bed rather than
      the ordinary standard cholecystectomy. Herein, we showed a partial hepatic
      resection of the gallbladder bed with the gallbladder using an intermittent
      hepatic inflow occlusion.

PMID- 16795967
TI  - Biological aggressiveness of alpha-fetoprotein (AFP)-positive gastric cancer.
AB  - BACKGROUND/AIMS: Alpha-fetoprotein (AFP)-positive gastric cancer (APGC) which
      occupied well-defined gastric cancer entity, reportedly has an aggressive
      behavior with hematogenous metastasis. However, little information regarding the
      clinicopathological and biological behaviors of APGC is available due to the
      small size of reported series. METHODOLOGY: We retrospectively analyzed the
      clinical features of APGC in 556 patients with gastric cancer who underwent
      preoperative measurement of serum AFP levels and gastrectomy in Kagoshima
      University Hospital. APGC was regarded as any cancer with preoperative serum AFP
      levels above the cutoff level of 5 ng/mL. Clinicopathological features of APGC
      were assessed using the General Rules of Gastric Cancer. Of the 556 patients, 97
      patients underwent immunohistochemical evaluation of AFP expression in the
      primary tumor. Both p53 and MIB-1 expression were examined at the same time and
      compared with AFP expression. Biological aggressiveness of APGC was estimated.
      RESULTS: Serum AFP positivity was detected in 4.3% of cases (range, 0-2202
      ng/mL). Patients were divided into 25 APGC patients and 531 non-APGC patients.
      APGC displayed deeper tumor invasion, increased nodal involvement, increased
      venous invasion, and increased CEA concentrations compared to gastric cancer in
      non-APGC. Surgical outcomes for APGC were significantly worse than those for non
      APGC (p < 0.05). All recurrences in patients with APGC involved hepatic
      metastasis. Abnormalities of p53 were more frequent for APGC than for non-APGC (p
      < 0.05). CONCLUSIONS: APGC was strongly associated with hematogenous factors such
      as venous invasion, hepatic metastasis and aggressive biological factors (p53
      abnormalities). Considering the aggressive biological behavior of APGC, we must
      closely follow up for patients with such tumor, including postoperative adjuvant
      therapy.

PMID- 16795968
TI  - Morphological changes in the lower esophageal sphincter influencing the result of
      antireflux surgical interventions in chronic gastroesophageal reflux disease.
AB  - BACKGROUND/AIMS: It is still unclear whether long-term reflux episodes result in
      morphological changes in the lower esophageal sphincter or not. If the answer is
      supposedly yes, do these changes influence the postoperative functional results
      following antireflux surgery? METHODOLOGY: Between 1 January 2002 and 2004, we
      performed antireflux surgery on 85 patients. Muscle samples were taken from the
      lower esophageal sphincter (LES) in 57 patients on operation. Patients with
      endoscopic findings of moderate or severe reflux esophagitis--Los Angeles B, C, D
      -were excluded. Control samples were obtained from muscle tissue at the
      gastroesophageal junction that had been removed from 16 patients undergoing
      gastric or esophageal resection. Histologic (hematoxylin and eosin and Giemsa),
      and immunohistologic (S-100 Protein, NCL-SERCA2, alpha-SMA) and
      electronmicroscopic analysis were used to evaluate the specimens. The number of
      smooth muscle cell nuclei in these intraoperative biopsies was used to compare
      the results of antireflux operations (Visick I and II-III). RESULTS: In 19%
      (11/57) of the reflux-type LES muscle samples perivascular inflammatory
      infiltration has been noted and in 6 of these cases (6/57 = 11%) this has
      incorporated marked intramuscular and adventitial granulocyte infiltration. In
      one patient (1/57 = 2%) eosinophil infiltration of the myenteric plexus and the
      ganglion has been revealed. Significantly lower Schwann and smooth muscle cell
      count could be detected in LES muscle samples taken from patients with GERD (p <
      0.05). The analysis of the values of the 9 patients in Visick groups II and III
      at two months after surgery, has shown a significant decrease in the number of
      smooth muscle cell nuclei as compared to those patients in Visick group I (p <
      0.01). CONCLUSIONS: Our results draw attention to the morphological changes
      occurring in the LES muscles of reflux patients. The enteric ganglionitis induced
      by GERD may result in various functional esophageal diseases. The histologic
      changes--that very much resemble hypertrophy--developing in LES muscles may serve
      as a reason for symptoms after antireflux surgery, presumably for the most common
      complaint of dysphagia.

PMID- 16795969
TI  - Clinical impact of 18F-FDG-PET in the suspicion of recurrent colorectal cancer
      based on asymptomatically elevated serum level of carcinoembryonic antigen (CEA)
      in Taiwan.
AB  - BACKGROUND/AIMS: To retrospectively evaluate the impact of 18F-fluorodeoxy
      glucose-positron emission tomography (FDG-PET) to detect recurrent colorectal
      cancer based on asymptomatically elevated tumor marker level of carcinoembryonic
      antigen (CEA). METHODOLOGY: Whole-body FDG-PET was performed in 50 patients
      suspected of having recurrent colorectal cancer and asymptomatically increased
      serum level of CEA (> 5 ng/mL), but other negative or equivocal imaging modality
      results. A blood sample was drawn in each case for CEA assay on the same day as
      the FDG-PET. The final diagnosis of recurrent colorectal cancer was established
      by operation/biopsy histopathological findings or clinical follow-up longer than
      1 year by additional morphologic imaging techniques. RESULTS: Among the 50
      patients, the final diagnosis of recurrent colorectal cancer was established in
      64 lesions of 45 patients. FDG-PET could accurately detect 62 lesions but missed
      2 false-negative lesions. In addition, there were 2 false-positive lesions. On a
      lesion-based analysis, the diagnostic sensitivity and positive predictive value
      of FDG-PET was 96.9%. There were 2 patients with false-negative lesions and 2
      patients with false-positive lesions. Therefore, FDG-PET findings could lead to
      successful surgical resection in 41 (82.0%) patients. In addition, on a patient
      based analysis, the diagnostic sensitivity and positive predictive value of FDG
      PET was 95.3%. CONCLUSIONS: FDG-PET is a useful technique for detecting recurrent
      colorectal cancer suspected by asymptomatically elevated serum level of CEA and
      has an important clinical impact on the management in patients with suspected
      recurrent colorectal cancer.

PMID- 16795970
TI  - Comparison of long-term outcome of laparoscopic and conventional surgery for
      advanced colon and rectosigmoid cancer.
AB  - BACKGROUND/AIMS: Although after laparoscopic surgery for colorectal cancer
      postoperative recovery is better than after open surgery, oncologic outcome after
      this minimally invasive technique remains unclear. In this study we tested the
      null hypothesis that there is no difference in the outcome of advanced colorectal
      cancer according to whether it is treated by laparoscopic or conventional open
      resection. METHODOLOGY: The long-term outcome of 79 patients with advanced
      colorectal cancer who underwent laparoscopic surgery between 1996 and 2002 was
      compared with that of 79 who underwent open surgery during the same period, being
      well-matched patients for age, gender, tumor site, and pathological TNM stage (II
      or III). Adjuvant therapy and postoperative follow-up were the same in both
      groups. RESULTS: The median follow-up time after laparoscopic and open surgery
      was 36 months and 47 months, respectively (p = 0.0756). No significant difference
      was found between the groups in overall or disease-free survival rates (96%
      versus 88%, p = 0.12; 96% versus 86%, p = 0.09, respectively). The recurrence
      rate was 23% in both groups, and liver metastasis was the most frequent form of
      recurrence. No port site recurrence was observed in the laparoscopic surgery
      group. CONCLUSIONS: The laparoscopic approach is an acceptable alternative to
      open surgery for advanced colorectal cancer because of the comparable medium-term
      outcome. Longer follow-up and large scale RCT is needed to fully assess the
      oncologic outcome.

PMID- 16795972
TI  - Urologic complications in Crohn's disease: suspicion criteria.
AB  - BACKGROUND/AIMS: Genitourinary complications occur in 4 to 35% of Crohn's disease
      patients. The aim of this study was to assess the threshold to suspect urologic
      involvement in Crohn's disease in order to plan the correct surgical management.
      METHODOLOGY: Medical records of 258 consecutive patients who have undergone bowel
      resection for Crohn's disease were reviewed. We evaluated recurrent urinary tract
      infections, fever, dysuria, pneumaturia, fecaluria, abdominal mass at palpation
      or lower back pain at percussion, abdominal ultrasound and computerized
      tomography scan reports. Univariate analysis and multivariate analysis were
      performed with Fisher exact and log-linear tests respectively. RESULTS: Urologic
      complications were found in 11 patients (4.3%). Fistulizing disease, female
      gender and inflammatory mass were significantly increased in Crohn's disease
      patients with urinary tract involvement (p < 0.01). Ultrasound and computerized
      tomography scan demonstrated good specificity, sensibility, positive and negative
      predicting values for urologic complications. CONCLUSIONS: In the presence of
      abdominal mass in a Crohn's disease patient, the following step should be
      abdominal ultrasound or computerized tomography scan to rule out involvement of
      the ureter that should be treated previously to improve the intraoperative
      picture and patient general status.

PMID- 16795971
TI  - Optimal interval from decompression to semi-elective operation in sigmoid
      volvulus.
AB  - BACKGROUND/AIMS: The initial non-operative decompression and subsequent semi
      elective operation is a common strategy in managing sigmoid volvulus. However,
      the optimal interval between decompression and operation is still unclear.
      METHODOLOGY: From 1994 to 2004, 25 patients operated on for sigmoid volvulus at
      the National Taiwan University Hospital were enrolled. The treatment strategy and
      clinical outcome in these patients were retrospectively reviewed and analyzed.
      RESULTS: Twenty-one patients underwent successful non-operative decompression
      initially, and the remaining 4 patients underwent emergent operation. Gangrene of
      the colon was found in 3 patients, and all of them eventually died of medical
      complications, i.e. multiple organ failure, pneumonia and myocardial infarction.
      One leakage but no mortality occurred in the patients undergoing semi-elective
      operation. The rate of postoperative complication was not significantly different
      between the patients operated on 2 days and more than 2 days after the
      decompression. CONCLUSIONS: The initial non-operative decompression and
      subsequent semi-elective operation results in a satisfactory outcome in managing
      sigmoid volvulus. In the view of surgical result, a two-day interval seems
      adequate for bowel preparation and optimization of the patient's condition.

PMID- 16795973
TI  - mRNA expression of inducible nitric oxide synthase, endothelial nitric oxide
      synthase and vascular endothelial growth factor in esophageal mucosa biopsy
      specimens from patients with reflux esophagitis.
AB  - BACKGROUND/AIMS: Nitric oxide (NO) production is elevated in the intestine and
      may contribute to intestinal injury during inflammation. However, how the
      expression of inducible NO synthase (iNOS) mRNA and endothelial NO synthase
      (eNOS) mRNA in the esophageal mucosa contribute to mucosal damage caused by
      reflux esophagitis remains unknown. Since vascular endothelial growth factor
      (VEGF) exerts its action on microcirculation, contributing to angiogenesis and
      inflammation, we examined the role of VEGF together with iNOS and eNOS on
      development of reflux esophagitis. METHODOLOGY: The mRNA expression levels of
      iNOS, eNOS and VEGF were measured in biopsy specimens from 25 patients with
      reflux esophagitis, using TaqMan PCR and reverse transcription PCR. RESULTS: The
      expression of iNOS mRNA in the esophageal mucosa increased parallel to the
      severity of the esophagitis. There were no significant differences between both
      eNOS and VEGF mRNA expression levels and the severity of the esophagitis. The
      existence of gastric mucosal atrophy, hiatus hernia, therapy and Helicobacter
      pylori infection did not affect the levels of mRNA expression. CONCLUSIONS: The
      accumulation of NO, produced by iNOS, was considered to be related to the
      exacerbation of reflux esophagitis. Therapeutic intervention that reduces NO
      production may thus be of use in preventing development of esophageal mucosal
      injury in patients with reflux esophagitis.

PMID- 16795974
TI  - Prognostic factors after chemoradiotherapy for patients with inoperable
      esophageal squamous cell carcinoma.
AB  - BACKGROUND/AIMS: It is important to clarify the predictive and prognostic factors
      for chemoradiotherapy (CRT) in patients with inoperable esophageal cancer.
      METHODOLOGY: Forty-one patients with inoperable advanced esophageal cancer were
      evaluated. The predictive factors for the response to CRT (low-dose 5-FU and
      Cisplatin (FP) therapy plus 60 Gy of radiation) and the prognostic factors after
      CRT were analyzed. RESULTS: Of the 41 patients, seven achieved complete
      remission, 21 achieved partial remission, nine showed no change and four showed
      progressive disease. The median survival time was 19 months in patients with a
      tumor response, compared to 7 months in patients with non-responsive tumors. Only
      the serum cytokeratin (CYFRA) level independently predicted the responsiveness to
      treatment. In the multivariate analysis, the serum CYFRA level and the p53 gene
      mutation independently influenced prognosis. CONCLUSIONS: The presence of a p53
      mutation in the biopsy specimen or a high serum CYFRA level may be predictive of
      an adverse therapeutic outcome.

PMID- 16795975
TI  - Modification of the procedure for esophageal reconstruction after resection of
      esophageal cancer.
AB  - BACKGROUND/AIMS: Reconstruction after esophagectomy is still associated with the
      highest risk of anastomotic leakage among all of the gastrointestinal
      anastomoses. In 1994, the reconstruction phase of our procedure was modified
      aiming to reduce the risk of anastomotic leakage. We evaluated usefulness of our
      modified procedure. METHODOLOGY: 32 patients before the modification of
      reconstruction were included in Group A, whereas Group B included 80 patients
      after the modification. In Group A, a thin gastric tube was constructed along the
      greater curvature. In Group B, the gastric tube was made thinner and longer. We
      were able to preserve a vessel feeding the terminal segment of the gastric tube
      that secured ample blood supply to this segment. The cut end of the cervical
      esophagus was anastomosed to the posterior wall of the gastric tube near the
      greater curvature, where adequate blood supply is available, and the anastomotic
      line was covered with omentum. RESULTS: In Group A, anastomotic leakage occurred
      in 15.6%. In Group B, minor leaks occurred 2.5%, indicating a marked decrease.
      CONCLUSIONS: The method of esophageal reconstruction currently performed at our
      department does not require special techniques, but the occurrence of anastomotic
      leakage is very low.

PMID- 16795976
TI  - Pleural effusions following endoscopic injection sclerotherapy for cirrhotic
      patients with esophageal varices.
AB  - BACKGROUND/AIMS: Endoscopic injection sclerotherapy is in widespread use for
      patients with esophageal varices. It is well known that pleural effusions are
      among complications following endoscopic sclerotherapy. However, there are few
      studies regarding the proportion of patients developing pleural effusions after
      sclerotherapy. METHODOLOGY: Between August 1991 and September 1998, 575
      endoscopic injection sclerotherapies were carried out in 128 patients. Chest
      radiographs were obtained prior to and 24 hours after all procedures. We also
      obtained other clinical data from all patients. RESULTS: In total, 17.7% of post
      sclerotherapy patients were diagnosed as having small amounts of pleural
      effusions. Logistic regression revealed pleural effusions after sclerotherapy to
      be associated with ascites, chest pain for 24 hours, total volume of sclerosant
      and submucosal injection of more than 4mL of sclerosant. In parallel with
      injection of an increasing amount of submucosal sclerosant, the proportion of
      patients with pleural effusion increased. CONCLUSIONS: Pleural effusions were
      related to ascites, chest pain for 24 hours, total sclerosant volume and
      submucosal injection of sclerosant.

PMID- 16795977
TI  - Aggressive endoscopic hemostasis for severe gastrointestinal bleeding in
      critically ill patients to decrease mortality.
AB  - BACKGROUND/AIMS: In critically ill patients, with gastrointestinal (GI) bleeding
      achieving endoscopic hemostasis has been reported to be often difficult, with a
      high rebleeding rate. The purpose of this study was to examine the efficacy of
      endoscopic hemoclipping for severe GI bleeding in critically ill patients.
      METHODOLOGY: This prospective study was performed at the Department of
      Traumatology and Critical Care Medicine, Kyorin University Hospital from June
      1996 to December 1999. Patients with predefined clinically significant GI
      bleeding were treated using an established endoscopic hemoclipping protocol that
      covered indications and procedures. RESULTS: A total of 1429 patients were
      enrolled in this study. Of 11 hospitalized cases meeting the definition of severe
      GI bleeding, it occurred at 12.3 +/- 3.9 days (mean +/- SD) after admission.
      Initial hemostasis was possible in all patients. Although rebleeding was seen in
      1 patient, the permanent hemostasis rate by additional endoscopic hemostasis was
      100%. Of the 11, 9 patients were discharged and there were 2 hospital deaths. The
      direct cause of death depended on the degree of underlying critical illness and
      combined severe pneumonia. Complications caused by endoscopic hemostasis were not
      seen in any patient. CONCLUSIONS: Endoscopic hemostasis is useful in critically
      ill patients with the severe GI bleeding that occurs during critical care in the
      intensive care unit.

PMID- 16795978
TI  - Gastrointestinal stromal tumors (GISTs): analysis of 20 cases.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas
      arising from the mesenchymal tissues in the gastrointestinal tract. Diagnosis,
      treatment and follow-up protocols of GISTs have not been exactly defined. In this
      study, twenty cases with GISTs treated in our clinic are examined
      retrospectively. METHODOLOGY: Twenty cases treated for GISTs in Izmir Ataturk
      Training and Research Hospital between the years 1999 and 2004 were reviewed
      retrospectively. Age, gender, clinical findings, diagnostic methods,
      intraoperative findings, type of surgery, histopathological findings and survival
      of the patients were evaluated. RESULTS: Fifteen of the cases were male (75%) and
      five were female (25%), with a median age of 55 years (35-80). The most frequent
      symptoms were abdominal pain and acute gastrointestinal bleeding. Tumors were
      gastric (40%), small intestinal (45%), colonic (10%) or rectal (5%). The median
      tumor size was 9.1 centimeters. Pathological evaluation showed that number of
      mitoses per 50 high-power field (hpf) was more than five in nine of 10 cases and
      CD-117 was positive in four of four cases. The mean follow-up period was 21 (1
      72) months, and median survival was 21 (1-72) months. CONCLUSIONS: The prognosis
      of GIST is frequently related to the tumor size and rate of mitosis. Despite the
      recent demonstration of C-kit protooncogene and introduction of imatinib mesilate
      as a new chance in treatment, radical surgery remains to be the most effective
      treatment of GISTs.

PMID- 16795979
TI  - Operative morbidity and mortality after D2 and D4 extended dissection for
      advanced gastric cancer: a prospective randomized trial conducted by Asian
      surgeons.
AB  - BACKGROUND/AIMS: A randomized study was performed to evaluate morbidity and
      mortality after D2 (level 1 and 2 lymphadenectomy) and D4 (D2 plus
      lymphadenectomy of para-aortic lymph nodes) dissection for advanced gastric
      cancer. METHODOLOGY: Two hundred and fifty-six patients with advanced gastric
      adenocarcinoma were enrolled (128 to each group). Patients were randomly
      allocated into D2 (N = 128) or D4 (N = 128) group. The first and second tiers of
      lymph nodes are removed in D2 dissection. In D4 gastrectomy, the paraaortic lymph
      nodes were additionally removed. RESULTS: There was no indication of significant
      distribution bias with regard to age, sex, T-grade, and N-grade between the two
      groups. Operation time of D4 gastrectomy (369 +/- 120 min) was significantly
      longer than that of D2 gastrectomy (273 +/- 1103 min), and blood loss of the D4
      group (872 +/- 683 mL) was significantly greater than that of the D2 group 571 +/
      527 mL (P < 0.001). Five (4%) and two (2%) medical complications developed in
      the D2 and D4 groups, respectively. Surgical complications developed in 28 (22%)
      and 48 patients (38%) after D2 and D4 gastrectomy. The most common complications
      were anastomotic leakage, pancreatic fistula, and abdominal abscess. Pancreatic
      fistula developed in 6 (19%) of 32 patients after D4 plus pancreatosplenectomy,
      but the incidence of pancreatic fistula after D2 gastrectomy plus
      pancreatosplenectomy was low (6%, 1/16). Two patients died within 30 days of
      operation (0.8%, 2/256), and each patient belonged to the D2 and D4 group.
      CONCLUSIONS: Although there is a significantly higher surgical complication rate
      in D4 dissection, D4 dissection can be done safely as D2 dissection when
      performed by well-trained surgeons.

PMID- 16795980
TI  - The etiology and clinical characteristics of acute lower gastrointestinal
      bleeding in patients hospitalized for comorbid illnesses.
AB  - BACKGROUND/AIMS: To determine whether there are different causes of acute lower
      gastrointestinal bleeding and different clinical courses in patients (a) with
      comorbid illnesses vs. (b) patients with only severe hematochezia. METHODOLOGY:
      From January 2001 to December 2003, 107 hospitalized patients with acute lower
      gastrointestinal bleeding were evaluated by urgent colonoscopy. Our analyses
      compared the etiology and clinical characteristics of bleeding in patients with
      (group A) and without (group B) one or more comorbid illnesses. RESULTS: Group A
      patients tended to have longer hospital stays, more severe anemic conditions, and
      more transfusion requirements. The overall mortality rate was 29.5% in group A
      and 4.3% in group B (p < 0.05). Bleeding-related mortality was not significantly
      different between groups. Colitis, rectal ulcer, and angiodysplasia were the
      leading causes of lower gastrointestinal bleeding in group A. Rectal ulcer was a
      more common cause of bleeding in group A (16.4%) than in group B (2.1%) (p <
      0.05), and it resulted in longer hospital stays and more severe anemia and
      leukocytosis compared to patients with other causes of lower gastrointestinal
      bleeding. CONCLUSIONS: Patients with acute lower gastrointestinal bleeding that
      starts after hospitalization for other comorbid illnesses have distinctive
      etiologies and clinical characteristics compared with ordinary patients admitted
      to the hospital with only bleeding. Rectal ulcer is an important but obscure
      cause of acute lower gastrointestinal bleeding in elderly patients with
      significant comorbid diseases.

PMID- 16795982
TI  - Preoperative systemic chemotherapy does not modify strategy of liver resection.
AB  - BACKGROUND/AIMS: Most patients who undergo surgical resection of colorectal liver
      metastases have been previously treated with chemotherapy as adjuvant therapy or
      as a primary treatment. The aim of this retrospective study was to compare
      morbidity, mortality, liver function and histology of the liver specimens in
      patients undergoing colorectal liver metastases (CRLM) resection with and without
      a history of previous chemotherapy. METHODOLOGY: Records of 210 patients who
      underwent CRLM resection in our institution between January 1996 and March 2003
      were retrospectively reviewed. We selected for further analysis medical charts of
      40 patients who didn't receive a combined treatment concurrently to liver
      resection. Group I included 25 patients who did not receive adjuvant
      chemotherapy. Group II included 15 patients who received chemotherapy in the 3
      months before liver resection. RESULTS: Postoperative mortality was 0% and 0.7%
      in group I and II respectively. Specific liver complications and pulmonary
      complications were similar in the two groups: 20% and 32% us. 33% respectively.
      The mean length of stay in the hospital was similar in the two groups (19 +/- 14
      vs. 14 +/- 8). Changes of liver function test were similar in the two groups.
      Pathologic examination of liver specimens was not different in the two groups.
      CONCLUSIONS: Preoperative systemic chemotherapy didn't increase the risk of liver
      resection.

PMID- 16795981
TI  - Choice of azathioprine or 6-mercaptopurine dose based on thiopurine
      methyltransferase (TPMT) activity to avoid myelosuppression. A prospective study.
AB  - BACKGROUND/AIMS: To prospectively evaluate whether, in patients with inflammatory
      bowel disease, the choice of azathioprine (AZA) or 6-mercaptopurine (6-MP) dose
      based on thiopurine methyltransferase (TPMT) activity prevents myelotoxicity.
      METHODOLOGY: TPMT activity in red blood cells was measured in 99 patients with
      Crohn's disease and 32 with ulcerative colitis prior to initiating AZA/6-MP
      treatment. AZA/6-MP dose was chosen based on TPMT activity, which was again
      determined one month after starting therapy. Incidence of adverse effects was
      evaluated for at least 6 months of follow-up. RESULTS: Mean basal TPMT value was
      21.6 +/- 5 U/mL. No patient had low levels (< 5 U/mL), 6.9% had intermediate
      levels (5-13.7 U/mL), and 93.1% had high levels (> 13.8 U/mL). In patients with
      Crohn's disease, mean TPMT activity significantly decreased after AZA/6-MP
      therapy, while in patients with ulcerative colitis this activity did not change.
      Among the 4 patients having myelotoxicity, one had intermediate basal TPMT
      levels, and 3 even had high levels, but no patient had low levels. CONCLUSIONS:
      In this prospective study we could not confirm that the choice of AZA/6-MP dose
      based on TPMT activity prevents myelotoxicity in patients with inflammatory bowel
      disease. Routine analytical controls should be performed in these patients
      independently of TPMT activity.

PMID- 16795983
TI  - Autologous tumor vaccine lowering postsurgical recurrent rate of hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: A tumor vaccine consisting of formalin-fixed hepatocellular
      carcinoma (HCC) tissue fragments, biodegradable sustained-releasers of
      granulocyte-macrophage-colony stimulating factor (GM-CSF) and interleukin-2 (IL
      2), and an adjuvant was developed. The aim of this study was to evaluate the
      effects of autologous tumor vaccine for protective immunity against HCC.
      METHODOLOGY: C57BL/6J mice were immunized intradermally with the Hepa1-6 tumor
      vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa1-6
      cells. On day 21, the tumor volumes were measured and the effect of tumor vaccine
      was evaluated. Lymphocytes from the immunized mice were cultured and the specific
      cytotoxicity against Hepa1-6 was accessed. Then from March 1999 to June 2003, 67
      patients with HCC undergoing curative resection were randomly divided into a
      tumor vaccine group (n = 32) and a control group (n = 35). Patients in the tumor
      vaccine group received 3 vaccinations at a 2-week interval and the control group
      only adjuvant treatment for symptoms. A delayed-type-hypersensitivity test was
      performed before and after vaccination. Primary endpoint was time to first
      recurrence and recurrent rates were analyzed. RESULTS: The tumor vaccine
      protected 87% of syngeneic mice from Hepa1-6 cells inoculation. In an in vitro
      experiment, splenocytes from the vaccinated mice exhibited a 56% lytic activity
      against the Hepa1-6 cells at an effector/target (E/T) ratio of 5, whereas they
      did not exhibit such activity against other tumor cells. The cytotoxic activity
      was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class II
      monoclonal antibodies but not with anti-CD4 and anti-MHC-class I antibodies. In
      clinical trial, thirty-two patients had completed the tumor vaccine procedure and
      no essential adverse effect occurred. The follow-up averaged 33.6 months (range
      from 15 to 54 months). The recurrent rate was significantly better in the tumor
      vaccine group (1 year, 12.6%; 2 years, 35.9%; 3 years, 54%) than in the control
      group (1 year, 31.6%; 2 years, 61.3%; 3 years, 72.1%; P = 0.037). 23/32 patients
      developed a DTH response against the fragments of HCC and DTH-response-positive
      patients had a lower recurrent rate than DTH-response-negative patients (7/23 vs.
      5/9). CONCLUSIONS: The autologous tumor vaccine is a promising adjunctive
      modality to prevent recurrence of human HCC.

PMID- 16795984
TI  - Surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus.
AB  - BACKGROUND/AIMS: To study the value of surgical treatment for hepatocellular
      carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODOLOGY: From January
      1997 to December 2001, 63 cases of HCC with portal vein tumor thrombus underwent
      liver resection combined with PVTT removal (group 1). Between December 2001 and
      December 2003, 20 patients received adjuvant portal vein chemotherapy (PVC) after
      the surgical procedures mentioned above (group 2). Treatment outcome and the
      surgical features in these two groups were studied. RESULTS: The median overall
      survival in group 2 was significantly longer than that in group 1 (10.9 months
      vs. 7.8 months, p < 0.05). There were significant differences between the
      survival of the two groups (log-rank, p < 0.05). In group 1 the 1-, 3-, and 5
      year survival rates were 18.0%, 14.8% and 1.6%, respectively. In group 2 the 1
      year survival rate was 30%. CONCLUSIONS: Liver resection combined with PVTT
      removal and the postoperative PVC is beneficial to the survival of HCC patients
      with PVTT. Postoperative PVC might enhance the effect of these surgical
      approaches.

PMID- 16795985
TI  - Factors participating in the development and mortality of variceal bleeding in
      portal hypertension--possible effects of the kidney damage and malnutrition.
AB  - BACKGROUND/AIMS: Acute bleeding from esophageal varices due to portal
      hypertension is a frequent and severe complication of liver cirrhosis. The
      development of esophageal varices as well as their rupture depends on the level
      of portal pressure; however, a number of other factors may play a negative role
      in the rise of bleeding and its prognosis. METHODOLOGY: The report presented has
      compared a set of 46 patients admitted to hospital for acute bleeding with 48
      cirrhotics hospitalized for other reasons. RESULTS: Bleeding patients had
      significantly higher level of nitrogenous substances (urea 14.1 mmol/L vs. 7.78
      mmol/L, p < 0.01, creatinine 129.8 micromol/L vs. 106.04 micromol/L; p = 0.09).
      The disturbed renal function in itself probably does not increase the risk of
      bleeding, it may be rather considered a certain prognostic index of the portal
      hypertension degree. Bleeding patients had a lower level of total protein (60.7
      g/L vs. 69.9 g/L; p < 0.01) with only slight insignificant decrease of albumin
      (26.64 g/L vs. 28.51 g/L). Cirrhotic patients are known to suffer from
      malnutrition and it is possible that malnutrition shares negatively and directly
      in the rise of bleeding. CONCLUSIONS: A prognostic index of mortality was a more
      conspicuous disorder of hepatic function (bilirubin 97.4 micromol/L vs. 57.4
      micromol/L; p = 0.1; prolonged prothrombin time 1.99 INR vs. 1.56 INR; p = 0.01)
      and again the disorder of renal function (creatinine 166.7 micromol/L vs. 114.9
      micromol/L; p = 0.09). Therefore, the maintenance of good renal function must be
      a component of complex therapy given to bleeding patients.

PMID- 16795987
TI  - Evaluation of CT during arterial portography for preoperative diagnosis of
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND/AIMS: To evaluate computed tomography during arterial portography for
      preoperative evaluation in patients with intrahepatic cholangiocarcinoma.
      METHODOLOGY: Computed tomography during arterial portography was performed in 11
      intrahepatic cholangiocarcinoma patients undergoing hepatectomy. Segmental
      perfusion defect, sensitivity of the main tumor, and sensitivity of intrahepatic
      metastasis on computed tomography during arterial portography were
      retrospectively evaluated. RESULTS: In 9 of 11 patients (81.8%), a segmental
      perfusion defect was seen. The sensitivities for detecting the main tumor and
      intrahepatic metastasis were 81.8% and 20%, respectively. In 2 patients, the main
      tumors existed in segmental perfusion defects and thus were not depicted. In 4
      false-negative cases, intrahepatic metastatic lesions existed in the segments
      that were the counterparts of segmental perfusion defects on computed tomography
      during arterial portography. CONCLUSIONS: The sensitivity of computed tomography
      during arterial portography for diagnosing intrahepatic cholangiocarcinoma and
      its intrahepatic metastasis was low due to segmental perfusion defect. It is
      necessary for intrahepatic cholangiocarcinoma to be subjected to systematic
      segmentectomy including all areas corresponding to the segmental perfusion
      defect.

PMID- 16795986
TI  - Survival of patients with colorectal cancer liver metastases treated by regional
      chemotherapy.
AB  - BACKGROUND/AIMS: Liver is the most common site of metastatic disease in
      colorectal cancer. Superior response rate was demonstrated in trials comparing
      hepatic arterial administration of cytotoxic agents with systemic chemotherapy.
      METHODOLOGY: Records of 109 consecutive patients with colorectal carcinoma
      metastatic to the liver treated by regional chemotherapy, who underwent
      implantation of a port system into hepatic artery or portal vein tributaries
      between 1991 and 1999, were reviewed and survival was evaluated using the log
      rank test and multivariate analysis (Cox's proportional hazard regression).
      RESULTS: The median survival from diagnosis was 24 months. Survival was
      significantly longer for patients treated by radical resection, and patients
      treated in 1997-1999. On multivariate analysis, treatment by 6 or more
      chemotherapy cycles, stage 1 liver metastases, treatment with irinotecan and
      radical resection were associated with better survival, while the presence of
      extrahepatic disease had an adverse effect on the risk of death. Extrahepatic
      spread was subsequently detected in almost half of the patients who had
      originally isolated liver metastases. CONCLUSIONS: Patients treated by liver
      resection had the best outcome, while patients with extrahepatic diseases had
      poor prognosis. The prognosis of patients treated by regional chemotherapy
      improved significantly with the advent of irinotecan and better selection.

PMID- 16795988
TI  - Surgical treatment for relief of severe pain with chronic pancreatitis that is
      resistant to conservative treatment.
AB  - BACKGROUND/AIMS: To evaluate the surgical treatment, we investigated that
      performed for chronic pancreatitis patients suffering from severe pain resistant
      to conservative treatments. METHODOLOGY: Nineteen chronic pancreatitis patients
      with severe pain resistant for a long time to previous conservative medical
      and/or interventional treatments underwent surgery retrospectively. We evaluated
      a difference of postoperative improvement of symptoms in patients with surgical
      treatment including nerve plexus resection. RESULTS: The mean follow-up interval
      after surgery was 59.7 months (range, 3.0-187.3 months). Of 19 patients, 14
      (73.7%) underwent nerve plexus resection. Relief of symptoms was observed in 16
      of 19 patients (84.2%). Fourteen of the 15 patients (93.3%) in the nerve plexus
      resection group were relieved of symptoms after surgery, compared to only two of
      four (50.0%) patients in the nerve plexus non-resection group. CONCLUSIONS:
      Surgical treatments with nerve plexus resection appropriately matched with
      individual patients are very safe and contribute to the improvement of the
      quality of life for chronic pancreatitis patients resistant to conservative
      treatments.

PMID- 16795990
TI  - Nodal involvement is strongest predictor of poor survival in patients with
      invasive adenocarcinoma of the head of the pancreas.
AB  - BACKGROUND/AIMS: Pancreatic cancer is a devastating disease with an extremely
      poor prognosis. The outcome of pancreatic head cancer after surgical resection is
      still difficult to predict. METHODOLOGY: Between September 1992 and December
      2003, 100 consecutive patients with invasive adenocarcinoma of the head of the
      pancreas who underwent surgical resection were retrospectively analyzed to
      clarify the influence of clinicopathological factors. RESULTS: The overall 1-, 3
      , and 5-year survival rates for the 100 patients with pancreatic head cancer were
      55%, 16%, and 6%, respectively. Among the 16 clinicopathologic factors, 9 were
      significantly associated with outcome in univariate analysis: tumor type
      (invasive ductal cancer), poor histological differentiation, extrapancreatic
      plexus invasion, bile duct invasion, duodenal invasion, intrapancreatic nerve
      invasion, lymphatic invasion, venous invasion, and nodal involvement.
      Multivariate analysis confirmed that nodal involvement (p = 0.005) and
      extrapancreatic plexus invasion (p = 0.03) were significant independent factors
      for overall survival. CONCLUSIONS: Nodal involvement was the strongest predictor
      of poor survival after pancreatic resection for invasive adenocarcinoma of the
      head of the pancreas.

PMID- 16795989
TI  - The lethal toxicity of pancreatic ascites fluid in severe acute necrotizing
      pancreatitis.
AB  - BACKGROUND/AIMS: The pathogenesis and the molecular mechanisms of the development
      and progression of the acute pancreatitis (AP) are not clearly understood.
      Ascites fluid is known to be important in the clinical progression of AP. We
      present the lethal toxicity of human pancreatic ascites fluid for experimental
      pancreatitis, with the therapeutic course of severe necrotizing AP. METHODOLOGY:
      The material was in a 33-year-old male admitted with epigastric pain. An
      abdominal CT revealed that his pancreas was swollen and contained pancreatic
      fluid collection extending to the pelvic cavity. He had complicated acute renal
      failure, sepsis, and DIC, and received hemodialysis, and continuous arterial
      infusion therapy (CAI). The peripancreatic infection was acquired, and
      percutaneous interventional radiology (IVR) was performed for the abscess
      drainage. The drained liquid around the pancreas contained high molecular
      cytokines, protease, and bacterial contamination. To evaluate the toxicity of the
      ascites fluid, we gave it intraperitoneally to rats in which pancreatitis had
      been induced and rats that had undergone a sham operation; these rats died
      immediately. The consistent irrigation and drainage of the abscess was
      administered and the patient's general condition improved. At this time, we gave
      the drained material intraperitoneally to other rats with induced pancreatitis
      and sham operation, but all these rats survived. RESULTS: These experimental
      results suggested that pancreatitis-associated ascites fluid contained a lethal
      toxicity. For curing this disease, elimination of these potential toxic mediators
      was essential. Our intensive IVR-based therapy improved the patient's prognosis.
      CONCLUSIONS: Downregulating this inflammatory process leads to a decrease in the
      mortality of severe acute pancreatitis.

PMID- 16795991
TI  - EGFR alterations in pancreatic ductal adenocarcinoma: a chromogenic in situ
      hybridization analysis based on tissue microarrays.
AB  - BACKGROUND/AIMS: To evaluate epidermal growth factor receptor (EGFR) gene status
      in pancreatic ductal adenocarcinoma correlating the results to protein expression
      and clinicopathological features METHODOLOGY: Using tissue microarray technology
      (TMArrayer 100), fifty (n = 50) paraffin-embedded tissue samples of
      histologically-confirmed primary tumors were cored twice at a diameter of 1 mm
      and re-embedded into the final recipient block. Immunohistochemistry was
      performed by the use of anti-EGFR monoclonal antibody (31G7). Also, a chromogenic
      in situ hybridization protocol was applied based on the use of EGFR gene and
      chromosome 7 centromeric probes, respectively. RESULTS: EGFR protein
      overexpression was observed in 29/50 (58%) cases and correlated to stage (p =
      0.001) but not to grade (p = 0.206). EGFR gene analysis identified numerical
      alterations in 6/50 (12%), including 2 cases characterized by low-level gene
      amplification and 4 by absence of one allele. Gene status was associated to tumor
      grade (p = 0.023) and stage (p = 0.02). Chromosome 7 analysis detected aneuploidy
      in 14 (28%) cases. CONCLUSIONS: A subset of pancreatic ductal adenocarcinomas
      (PDACs) is characterized by EGFR gene numerical alterations including sporadic
      cases of amplification or absence of one allele (maybe due to gene deletion or
      intragenic point mutation and allelic silence). Those alternative mechanisms
      maybe influence the efficacy of novel targeted therapeutic strategies based on
      monoclonal antibodies or intracellular tyrosine-kinase inhibitors in PDACs.

PMID- 16795992
TI  - Intratumoral heterogeneous expression of thymidylate synthase in gastric cancer.
AB  - BACKGROUND/AIMS: Thymidylate synthase (TS) is reported to be a predictive factor
      of survival in gastric cancer patients. Its heterogeneous expression has been
      observed in various cancerous lesions but has not been assessed intratumorally.
      The aim of this study was to determine the most pertinent site for investigating
      intratumoral TS expression for the prediction of survival. METHODOLOGY: TS
      staining grade was evaluated at the center (CT), the horizontal edge (HT) and the
      vertical edge (VT) of the tumor, and TS protein level was determined by ELISA at
      CT and HT. Proliferating cell nuclear antigen (PCNA) was examined for
      proliferation markers in all tumor samples. RESULTS: TS expression at HT and VT
      was significantly higher than at CT. A positive correlation was observed between
      TS protein level and PCNA-Labeling Index at HT, but not at CT. The survival rate
      of the high TS group was poor compared with the low TS group at HT and VT, but
      not at CT. CONCLUSIONS: The horizontal edge of the tumor (HT) is the most
      pertinent site for the evaluation of TS expression in gastric cancer; it could
      prove especially useful in the presurgical estimation of prognosis through biopsy
      samples.

PMID- 16795994
TI  - Distribution of lymph node metastasis in gastric carcinoma.
AB  - BACKGROUND/AIMS: In gastric cancer, appropriate lymph node dissection increases
      survival, and hence it is of value to determine lymph node metastasis
      distribution in the early phase of progression. METHODOLOGY: This study involved
      a series of 274 consecutive patients with 1-6 lymph node metastases occurring
      after resection. The pattern of lymph node metastases was analyzed
      retrospectively. RESULTS: Of 102 patients with single lymph node metastasis, over
      60% of metastases occurred in specific lymph nodes for each tumor. However, the
      remainder was scattered in an unpredictable manner including the para-aortic
      lymph nodes. Despite variations in invasiveness of tumors in patients with a
      single lymph node, the distribution remained unchanged. Nor was there any change
      in patients with an increased number of metastatic lymph nodes. However, in the
      latter group a higher proportion of metastases were widespread. About 85-90% of
      node was located within paragastric lymph nodes. CONCLUSIONS: Over 60% of
      metastatic lymph nodes would be eliminated by the dissection of specific areas
      determined by the site of the tumor. If the concept of sentinel lymph nodes in
      gastric cancer is valid, navigation surgery will be necessary for patients with
      early gastric cancer to locate such unpredictable metastasis.

PMID- 16795993
TI  - Multiple primary cancers in patients with gastric cancer.
AB  - BACKGROUND/AIMS: Some gastric cancer patients have multiple primary cancers
      (MPC). We evaluate the current status of MPC with gastric cancer. METHODOLOGY:
      2,109 gastric cancer patients treated between 1987 and 2002 were analyzed.
      RESULTS: There were 99 MPC with gastric cancer (4.7%). Second cancer (77.8%) was
      discovered within 5 years before and after the onset of gastric cancer. 34.3% of
      patients were discovered within 1 year (synchronous tumor). In the 77 male
      patients, prostate cancer was the most common occurrence (19.5%), followed by
      cancers of the colon (18.2%) and liver (14.3%). In the 22 female patients, colon
      cancer was the most common (31.9%) followed by breast and cervix cancers (22.7%).
      These cancers were the most common diseases in Taiwan in the same period. Gastric
      cancer patients with MPC had less stromal reaction and better survival than those
      without. Patients with metachronous secondary tumors had more peritoneal
      dissemination and worse survival than those with synchronous primary cancer.
      CONCLUSIONS: Gastric cancer patients may develop second cancer(s), which is often
      a current prevalent malignancy. Knowledge of time to development and mode of
      organ association may allow clinicians to detect potentially curable subsequent
      cancer(s).

PMID- 16795995
TI  - Therapeutic outcomes of continuous hyperthermic peritoneal perfusion against
      advanced gastric cancer with peritoneal carcinomatosis.
AB  - BACKGROUND/AIMS: To clarify the efficacy of therapeutic continuous hyperthermic
      peritoneal perfusion in peritoneal carcinomatosis of gastric cancer. METHODOLOGY:
      The subjects of this study were 73 advanced gastric cancer patients who underwent
      palliative surgery between 1992 and 1999. Therapeutic continuous hyperthermic
      peritoneal perfusion (T-CHPP) was performed in 21 patients, who had macroscopic
      peritoneal carcinomatosis or positive lavage cytology, were under 65 years old,
      had no concomitant disease, and gave informed consent. Fifty-two patients who did
      not meet the inclusion criteria formed the control group. After reconstruction of
      the alimentary tract, T-CHPP was carried out for 40 min with 300 mg of Cisplatin,
      30 mg of mitomycin C, and 300 mg of etoposide in 5-6 L of physiological saline
      maintained at 42 degrees C to 43 degrees C. RESULTS: The survival of patients who
      had CY1, P1, P2, P3 was not affected by T-CHPP. Univariate analysis revealed that
      the degree of peritoneal carcinomatosis and adjuvant chemotherapy were prognostic
      factors. Furthermore, ill-defined macroscopic appearance and P3 independently
      affected prognosis, according to multivariate analysis. Patients treated by T
      CHPP had higher incidences of respiratory failure (76.2% vs. 17.3%; p < 0.0001)
      and renal failure (14.3% vs. 0%; p < 0.0054) than those undergoing T-CHPP.
      CONCLUSIONS: As T-CHPP had no efficacy, a new therapeutic strategy such as
      chemosensitivity assessment or a well-structured randomized controlled trial is
      necessary to obtain good therapeutic results with T-CHPP.

PMID- 16795996
TI  - The effects of weight load and joint immobilization on reorganization of postural
      tremor.
AB  - To investigate change in coordinative strategies due to wrist immobilization and
      index loading, postural tremors from the index, hand, and forearm were recorded
      during different postural holding tasks. The wrist joint was immobilized with a
      thermoplastic splint in the constrained condition, and a copper mass of 100 grams
      was applied to the index finger in the loaded condition. The structures of the
      postural tremors of all upper limb segments among the unloaded-unconstrained,
      unloaded-constrained, loaded-unconstrained, and loaded-constrained conditions
      were compared. Index loading exaggerated index/forearm postural tremor, while the
      load-induced tremor enhancement was no longer evident for wrist immobilization.
      In the unloaded condition, wrist immobilization resulted specifically in
      enhancement of carpal postural tremor, rather than in the index and forearm.
      Index loading induced a marked tremor peak and relative power in the range of 5-8
      Hz. Wrist immobilization potentiated the carpal tremor peak of 1-4 Hz in
      association with enhancement of carpal-forearm mechanical coupling. In light of
      structural changes in postural tremor, our data suggest that (1) a wrist splint
      is effective to counteract load-induced enhancement of postural tremor, and (2)
      freezing of the wrist joint might facilitate compensatory strategies to minimize
      passive fluctuation transmission from the carpal to index.

PMID- 16795997
TI  - Correlation between the biceps brachii muscle bulk and the size of its evoked
      compound muscle action potential.
AB  - This study was to determine if the size of the compound muscle action potential
      (CMAP) recorded from a large muscle, such as the biceps brachii, can be
      correlated with the muscle mass or volume that is generating the electrical
      response. Supramaximal CMAPs were obtained from 32 normal biceps brachii muscles
      to electrical stimulation of the musculocutaneous nerve at the axilla. Upper-arm
      circumference was measured with biceps muscle relaxed (elbow extended) and during
      muscle contraction (elbow flexed). For all muscles, mean CMAP duration was 16.45
      ms, amplitude was 10.50 mV, and area was 96.13 mVms. Body mass index and absolute
      upper-arm circumference (biceps muscle relaxed or contracted) did not correlate
      with CMAP duration, amplitude, and area; Pearson correlation coefficients (r)
      ranged from -0.24 to 0.16. However, the difference (increment) in upper-arm
      circumference due to biceps muscle contraction correlated with CMAP duration (r =
      0.47), amplitude (r = 0.67), and area (r = 0. 75). CMAP size (amplitude and area)
      correlated well with biceps brachii muscle volume as estimated by the increase
      from baseline in upper-arm circumference during muscle contraction. The
      difference (increment) in upper-arm circumference due to biceps muscle
      contraction reflects mainly the underlying biceps muscle bulk, and eliminates
      other variables such as thickness of the subcutaneous tissues and triceps brachii
      muscle.

PMID- 16795998
TI  - Angle- and velocity-specific alterations in torque and semg activity of the
      quadriceps and hamstrings during isokinetic extension-flexion movements.
AB  - The purpose of this study was to investigate the effect of movement velocity (100
      degrees, 200 degrees , 300 degrees s(-1), and 400 degrees s(-1)) and joint
      position (0 degrees - 15 degrees [L0], 25 degrees - 40 degees [L25], 55 degrees -
      70 degrees [L55], and 75 degrees - 90 degrees [L75]) on peak torque (PT)
      parameters and surface electromyography (SEMG) of the knee-joint muscles during
      reciprocal isokinetic extension and flexion movements. Thirteen subjects (age =
      22.7 +/- 2.1 years, mean height = 161.1 +/- 6.6 cm, mean weight = 63.5 +/- 5.8
      kg) participated in the study. Bipolar surface electrodes were placed over the
      vastus medialis, vastus lateralis, biceps femoris, and medial hamstrings for
      determination of the root mean square (SEMGrms) and median frequency (SEMGmf) of
      the SEMG. Peak torque, angle of peak torque (PTang), percentage of peak torque
      (PTper), SEMGrms, and SEMGmf were analyzed using separate repeated measures
      analysis of variance (ANOVA). The following main results, significant at p < or =
      0.05 or better, were found: The PTang was influenced by movement velocity (in
      extension there was a decrease in PTang moving from 300 degrees x s(-1) to 400
      degrees x s(-1) and inflexion there was an increase in PTang moving from 300
      degrees x s(-1) to 400 degrees x s(-1)). Secondly, a greater percentage of peak
      torque (PTper) was maintained during knee flexion than knee extension. And
      thirdly, both the quadriceps and hamstrings exhibited changing amplitudes and
      spectral frequencies based on joint position and movement velocity. There was a
      trend of decreasing SEMGrms for the quadriceps as the knee moved into extension,
      and a lower SEMGmf during early (L75) and end stages of knee extension (L0). For
      the hamstrings, SEMGrms was lowest at the more shortened position (L75) and
      highest near the mid-position (L25); the lowest SEMGmf occurred at the more
      lengthened position (L0) and the highest occurred at the more shortened position
      (L75). Finally, velocity influenced hamstrings and quadriceps muscle amplitude
      such that SEMGrms was highest at the slower velocities and lowest at the higher
      velocities. Velocity had no impact on quadriceps spectral properties (p > 0.05),
      but had a cyclic effect on hamstrings spectral properties. Changes in amplitude
      and frequency spectrum in tested muscles could be explained, in part, by neural
      drive to these muscles. Data support the hypothesis of lower activation levels of
      the quadriceps muscle in the extended position espoused by several authors as a
      way to protect the knee-joint in the knee-extended position.

PMID- 16795999
TI  - Down beat nystagmus in vitamin B 12 deficiency syndrome.
AB  - A 34 years old male, presenting with progressive proximal weakness, with a
      neurogenic pattern on needle EMG, and a family history suggestive of an autosomal
      recessive disorder, was found to have additional features of myeloneuropathy and
      a down beat nystagmus. A low serum vitamin B12 level was found, and on vitamin
      B12 supplementation there was a partial clinical as well as electrophysiological
      recovery.

PMID- 16796000
TI  - Parallel auditory vestibular evoked neurogenic and myogenic potential results in
      a case of peripheral vestibular dysfunction, showing that the former originates
      from the vestibular system.
AB  - PURPOSE: Vestibular evoked myogenic potentials (VEMPs) uses high intensity clicks
      with recording from the tonically active sternocleidomastoid muscle, taking
      advantage of the close proximity of the saccule to the oval window. Our group has
      used the same stimulus to record Vestibular Evoked Neurogenic Potentials (VENPs)
      directly from the brain. VEMPs are now regarded the electrophysiological gold
      standard in peripheral vestibular system examination. We present a case of
      peripheral vestibular dysfunction to show that both VEMPs and VENPs provide
      similar results during recovery. METHODS: A case of Meniere's Disease in recovery
      is examined. VEMPs were recorded using a 105 dB nHL click stimulus from the
      ipsilateral sternocleidomastoid muscle. VENPs were recorded using an ipsilateral
      parietal to Fpz montage and a 1 kHz tone-pip stimulus. Standard BAEPs and
      threshold latency series (TLS) were performed. RESULTS: VEMP and VENP were
      unobtainable from the left side at initial presentation in a patient with
      Meniere's Disease, with normal BAEP and TLS bilaterally. After one month of
      therapy both the VEMP and VENP normalized. CONCLUSIONS: As VEMPs are known to
      originate from the vestibular system, the parallel VENP result suggests the same
      for the latter VENP may prove to be useful and complement VEMP in determining
      vestibular dysfunction.

PMID- 16796001
TI  - Coactivation patterns of the medial and lateral hamstrings based on joint
      position and movement velocity during isokinetic movements.
AB  - The purpose of this investigation was to determine the effect of movement
      velocity (100 degrees x s(-1), 200 degrees x s(-1), 300 degees x s(-1), and 400
      degrees x s(-1)) and joint position (0 degrees - 20 degrees [L0] 30 degrees - 50
      degrees [L30], and 70 degrees - 90 degrees [L70] knee flexion) on reciprocal
      coactivation patterns of the medial and lateral hamstrings as determined by the
      amplitude and frequency spectrum of surface electromyography (SEMG). Thirteen
      female subjects (age = 22.7 +/- 2.1 years, mean height = 161.1 +/- 6.6 cm, mean
      weight = 63.5 +/- 5.8 kg) participated in the study. Bipolar surface electrodes
      were placed over the biceps femoris (BF) and medial hamstrings (MH) for
      determination of the root mean square (SEMGrms) and median frequency (SEMGmf) of
      the SEMG. Normalized SEMGrms values for the MH and BF were determined as a
      percentage of agonist SEMGrms activity for the same muscle during its agonist
      phase. Data were analyzed using separate 2 x 3 x 4 (muscle x position x angular
      velocity) repeated measures analysis of variance (ANOVA). For SEMGrms, there were
      significant muscle (p < 0.01) and position (p < or = 0.0001) main effects. Post
      hoc analyses indicated the BF displayed greater muscle amplitude than the MH and
      that there was greater muscle amplitude at the L0 position (as the knee
      approached terminal extension). No velocity effect was noted (p > 0.05). For
      SEMGmf there were muscle x position (p < or = 0.05) and muscle x position x
      velocity (p < or = 0.01) interaction effects. Post-hoc analyses indicated the BF
      displayed a higher frequency spectrum than the MH at the L0 position. Secondly,
      velocity affected the BF and MH frequency spectrum such that values for both the
      MH and BF were lowest at 200 degrees x s(-1) and highest at 300 degrees x s(-1)
      (BF) and 400 degrees x s(-1) (MH). Velocity had little impact on the frequency
      spectrum in the midrange of the ROM (L30 position). Higher SEMGrms and SEMGmf
      values for the BF could be explained by the locking or screw home mechanism of
      the knee, and a way in which the human motor control system provides the limb
      with a dynamic braking system to control both extension and lateral rotational
      forces during the final stage of knee extension. It would appear that the way in
      which the body performs this function is not only to increase the amplitude of BF
      muscle firing but also to shift toward the recruitment of more fast-twitch motor
      units.

PMID- 16796002
TI  - Carpal tunnel syndrome: comparison of the compound muscle action potentials
      recorded at the thenar region from ulnar and median nerve stimulation.
AB  - Thenar muscles are primarily innervated by the median nerve. However, compound
      muscle action potentials (CMAPs) evoked by ulnar nerve stimulation can be
      recorded at the thenar region due to proximity of some ulnar-innervated muscles,
      and from volume conduction events. This study was to determine if loss of thenar
      muscle mass from carpal tunnel syndrome (CTS) could alter the size of ulnar CMAPs
      obtained at the thenar region, because of changes in the physical surroundings
      and electrical conductivity. Supramaximal CMAPs were recorded over the thenar
      eminence to electrical stimulation of the ulnar nerve at the wrist and median
      nerve at the palm in 102 hands with CTS. Needle EMG was done in the thenar
      muscles. Severity of needle EMG abnormality was negatively correlated with median
      evoked CMAP amplitude (r = -0.76), but not with ulnar-evoked CMAP amplitude (r = 
      0.12). There was no correlation between the absolute amplitudes of the median and
      ulnar CMAPs (r = -0.13). Needle EMG abnormality had modest negative correlation
      (r = -0.43) with median/ulnar CMAP amplitude ratio. Mean median/ulnar CMAP
      amplitude ratios for normal EMG and for mild, moderate, and severe needle EMG
      abnormalities were 3.72, 3.31, 1.56, and 0.37, respectively. The absolute
      amplitude of the ulnar CMAP recorded at the thenar area does not seem to be
      influenced significantly by the degree of thenar muscle loss (atrophy) from
      median nerve pathology. However, if the median/ulnar CMAP amplitude ratio falls
      below 0.5, the study suggests severe loss of motor units in the thenar muscles.

PMID- 16796003
TI  - Area-pressure relationship of lower limb main veins in man.
AB  - BACKGROUND: The mechanical properties of human veins remain incompletely known.
      However they play an important part in number of physiological and pathological
      situations, as hemodynamic adjustment to orthostasis, deep venous thrombosis
      (DVP) and chronic venous insufficiency (CVI). The aim of the study was to
      describe the pressure/volume (area) relationship of some important conduit veins
      of the human's lower limb. PROBANDS AND METHODS: We investigated the
      area/pressure relationship of thefemoral vein (FV) at mid thigh, the great
      saphenous vein (GSV) at lower third of the leg, and a deep leg vein (DLV), either
      the peroneal or posterior tibial vein, in fifteen healthy young men. The cross
      section areas were measured with B-mode ultrasound while various positive and
      negative venous pressures were generated by body's tilting. RESULTS: Over the
      range of pressures investigated, the area/pressure relationship was roughly
      linear, the classical sigmoid relation did not emerge from our data. The relative
      compliance of FV, GSV and DLV was 0.0312, 0.0118, and 0.0147 mmHg(-1),
      respectively. CONCLUSIONS: The relative compliance of FV is more than two times
      higher than the relative compliance of both the DLV and the GSV.

PMID- 16796004
TI  - Congenital vascular malformations: the persistence of marginal and embryonal
      veins.
AB  - BACKGROUND: In about 18% of cases with conginental vascular malformations we find
      a perspective of an atypical truncular vein, located along the outside of the
      leg, frequently extended from the dorsal foot up to the bottom. In presence of a
      normally developed system of the deep collecting veins of the lower limb and
      within the pelvic outflow we are talking about a persisting marginal vein (MV).
      Hypoplasia or even aplasia of the main deep veins in contrary defines the
      persisting embryonal vein (EV). Already in childhood these truncular dysplastic
      veins tend to develop varicose enlargement, causing severe reflux of a huge
      volume of blood--even more when being associated with av-fistulas (46%). In
      consequence a rapidly growing chronic venous insufficiency will guide to
      additional injuries. PATIENTS AND RESULTS: We have analysed 97 patients showing a
      persisting MV (n: 92 ) within a total of 102 legs. A persistent embryonal vein
      (EV) was seen 10 times within this clientel. The persisting truncular veins,
      associated with phlebectasias and typical clinical symptoms have been examined in
      a diagnostic "step-by-step" procedure, mainly phlebographically (ascending leg
      phlebography and varicography), including direct venous blood pressure
      measurements (phlebodynamometry) and--if needed--by arteriography, showing av
      shunting fistulae in 46% of cases. CT and MRI were consulted for the exact
      therapy planing (frequently initially offered as a non-invasive, however,
      inadequate key of diagnostic). Actually now these techniques cannot replace pre
      operatively the angiographic imaging techniques. CONCLUSIONS: The analysis of
      clinical, morphologic and functional signs, guiding to a specific therapy
      relevant classification of MV's and EV's will be presented. And a specific
      strategy of surgical repair, interventional treatment of av-fistulas and
      conservative compressive follow-up treatment attempting palliative recompensation
      of the diseased venous outflow will be discussed also.

PMID- 16796005
TI  - Detailed plaque texture analysis as the alternate method of ultrasound image
      analysis in predicting the risk of intraoperative microembolism and perioperative
      complications.
AB  - BACKGROUND: The aim of the study was to assess the value of an alternative method
      of carotid plaque ultrasound image analysis in relation to the perioperative
      complications and the main risk factor: the microembolism (ME). MATERIAL AND
      METHODS: 96 plaques were evaluated following carotid endarterectomy.
      Preoperatively, each plaque was screened by ultrasound and assessed by means of 2
      computer assisted methods. All patients were evaluated for ME (measured as hits)
      intraoperatively. The removed plaques were assessed visually (intraoperative
      assessement) and histologically. A number of risk factors were included as a
      final outcome event for the purpose of multivariate regression analysis. RESULTS:
      Detailed plaque texture analysis (DPTA) predicts best the risk of perioperative
      complications and ME (p = 0.029 and p = 0.028 respectively). The results of the
      standard gray-scale median (GSM) analysis did not reach the statistical
      significance (p > 0.1). The predictive value of the model (ROC) was 0.88. The
      multivariate model for ME revealed that from the level of > 5 HITS, a rapid
      increase in the risk of perioperative complications (rise of 5% by every 1 hit)
      is seen and correlates well with the DPTA. ROC was 0.77. A direct correlation
      between the DPTA and perioperative ME was shown. CONCLUSIONS: DPTA analysis of a
      carotid plaque is more predictive of the likelihood of microembolism than the GSM
      analysis. There is a direct correlation between the perioperative ME and plaque
      morphology, as assessed by DPTA. This supports the need for further refinements
      in noninvasive analysis of carotid plaques.

PMID- 16796006
TI  - Duplex scanning compared with intra-arterial angiography in diagnosing peripheral
      arterial disease: three analytical approaches.
AB  - BACKGROUND: This study was undertaken to assess the reliability of duplex
      scanning, as compared with digital subtraction angiography, in diagnosing
      peripheral arterial disease of the lower limbs. PATIENTS AND METHODS: 60 legs
      were studied. Each leg was divided in 5 arterial segments, from aortoiliac to
      popliteal. Duplex scanning and digital subtraction angiography were performed.
      The disease in each segment was assessed as significant or insignificant or
      classified into five categories concerning the grade of stenosis (patent vessel
      or no diameter reduction, mild stenosis, i.e. 1-19% diameter reduction, moderate
      and severe stenosis, i.e. 20-49% and 50-99% diameter reduction, respectively, and
      occluded vessel). Three statistical approaches were applied: calculating
      sensitivity and specificity, Kappa statistics, and weighted Kappa value. Median
      grades of arterial stenosis across different segments, according to angiography
      measurements, were also calculated. RESULTS: The duplex sensitivity in detecting
      significant lesions ranged from 0.46 to 0.88. The Kappa values of agreement
      between duplex and angiography ranged from 0.35 to 0.64. Weighted Kappa values
      ranged from 0.45 to 0.72. Median grades of arterial lesions ranged from 2
      (interquartile range 1-2) to 4 (3-4) and differed significantly (Kruskal-Wallis H
      test, p < 0.001). CONCLUSIONS: The sensitivities and specificities suggested
      various duplex reliabilities in detecting significant arterial disease across
      different lower limbs segments. The Kappa values, in general, testified duplex's
      insufficient accuracy in grading the severity of stenosis. However, weighted
      Kappa values confirmed duplex's better ability to approximate the grade of
      stenosis. The arterial segments themselves were unevenly affected with the
      peripheral arterial disease.

PMID- 16796008
TI  - Antiplatelet therapy prior to carotid endarterectomy--still room for improvement.
AB  - BACKGROUND: Antiplatelet therapy is one of the most important modalities for
      secondary prevention of ischemic events. The aim of this prospective study was to
      evaluate the current practice of antiplatelet therapy in patients with high grade
      stenosis of the internal carotid artery (ICA), who were referred by neurologists,
      stroke physicians and cardiologists for carotid endarterectomy. PATIENTS AND
      METHODS: Patients referred to our department for carotid endarterectomy with ICA
      stenosis (> 70% according to NASCET criteria) were prospectively evaluated
      regarding atherosclerosis risk factors and current antiplatelet therapy. During a
      7 month period, 235 patients were scheduled for carotid endarterectomy. Their
      mean age was 70 years (range 42 years to 95 years), 91 patients were female
      (39%), 144 male (61%). 122 patients (52%) had a symptomatic ICA stenosis, 113
      (48%) an asymptomatic ICA stenosis. RESULTS: Of the 235 patients, 29 were either
      on low molecular weight heparin or vitamin K antagonists for reasons other than
      ICA stenosis and were therefore excluded from analysis. Therefore, 206 patients
      (88%) were evaluated for antiplatelet therapy prescribed by their admitting
      physicians. Of these patients, 77 (37%) (42 (41%) symptomatic and 35 (34%)
      asymptomatic patients) did not receive any antithrombotic therapy prior to
      admission for surgery. The majority of patients received aspirin preoperatively
      (106 patients, 51.5%) 13 (6%) patients were on clopidogrel and 10 (5%) on dual
      therapy with Aspirin and clopidogrel. CONCLUSIONS: More than one third of
      patients awaiting carotid endarterectomy did not receive any antiplatelet
      therapy, despite high grade ICA stenosis. Since this practice does not meet the
      current guidelines, campaigns to increase the awareness of this problem are
      urgently needed.

PMID- 16796007
TI  - Influence of HMG-CoA-reductase inhibitors on the body fat status.
AB  - BACKGROUND: While the literature has conclusively shown a significant decrease of
      plasma lipids after intake of HMG-CoA reductase inhibitors, there is no detailed
      information provided about their effects on the body fat status. PATIENTS AND
      METHODS: We performed a retrospective analysis of a prospective randomized
      controlled trial including consecutive patients with suspected arterial occlusive
      disease. Normolipidemic patients served as the control group and hyperlipidemic
      patients were randomized to either 20 mg atorvastatin or to 40 mg simvastatin. At
      baseline, after 6 weeks and after 6 months we assessed the relative body fat, the
      waist circumference and the body mass index (BMI) as well as plasma total
      cholesterol (chol), low-densitiy lipoprotein cholesterol (LDL) and triglycerides
      (TG). RESULTS: In total we included 129 patients in our analysis. The body fat
      status remained unchanged in the control group as well as in the atorvastatin
      group (all p > 0.05) for the whole study period, while simvastatin treatment led
      to a slight, but significant increase of the relative body fat (+ 4.2%) between
      the 6 weeks and 6 months assessment (p = 0.013). CONCLUSIONS: Long-term intake of
      statins seems to have no positive influence on parameters of the body fat status
      and therefore misses one important goal in the cardiovascular risk prevention.

PMID- 16796009
TI  - Concomitant neurological and orthopaedic diseases in the presence of peripheral
      arterial disease: a prospective study.
AB  - BACKGROUND: The symptoms of peripheral arterial disease (PAD) can be masked by
      neurological or orthopaedic diseases with identical symptoms, which may result in
      faulty therapy decisions, if the diagnosis is solely based on the reported
      complaints and angiographic or duplex ultrasonographic findings. A prospective
      study was therefore performed to find out how often established PAD is
      accompanied by neurological or orthopaedic pictures that can blend into the PAD
      symptoms. PATIENTS AND METHODS: The examination was performed in 235 patients
      with PAD of Fontaine's stages II to IV, 125 were women and 110 men; the mean age
      was 71 years (41 to 95 years). They were systematically examined for angiologic,
      neurological and orthopaedic diseases. RESULTS: 44% of the patients enrolled in
      the study suffered from a neurological disease, 45% from an orthopaedic disease
      and 24.7% from both a neurological and an orthopaedic disease. The frequency of
      concomitant diseases depended on the stage of PAD. In Fontaine's stage II,
      alterations due to arthrosis or arthritis were found in 12% of the patients,
      peripheral neuropathies in 14%, radiculoneuropathies in 16% and malpositions of
      the foot in 16%. In Fontaine's stage III, arthrosis and arthritis were
      predominant at a percentage of 38.5%; peripheral neuropathies were diagnosed in
      15.4% of the patients. Patients with Fontaine's stage IV most often showed
      peripheral polyneuropathies at 42.1% and malpositions of the foot at 28.4%.
      CONCLUSIONS: Because of the frequency of neurological and orthopaedic pictures
      with identical symptoms, a differential diagnosis before the initiation of a PAD
      therapy is imperative.

PMID- 16796010
TI  - Acute mesenteric ischaemia, a highly lethal disease with a devastating outcome.
AB  - BACKGROUND: Acute mesenteric ischaemia remains a serious condition requiring
      emergency, surgical management. The mortality rate still remains high, due to the
      unspecific and delayed diagnosis and ranges from 59% to 100%. Purpose of our
      study is to present our experience in the management of the disease. PATIENTS AND
      METHODS: This is a retrospective study of 61 patients treated surgically for
      acute mesenteric ischaemia, between 1988 and 2004. All patients underwent a
      laparotomy. 75% of the patients were operated within the first 24 hours and the
      rest within 48 hours. RESULTS: Superior mesenteric artery embolism occurred in 36
      (59%), thrombosis in 21 (34%) and superior mesenteric vein thrombosis in 4 (7%)
      cases. In 49 (80%) cases, embolectomy or thrombectomy of the superior mesenteric
      artery with resection of the necrotic segment of the bowel was performed. Twelve
      cases (20%) were considered inoperable because of massive bowel necrosis.
      According to our study mortality and morbidity rate amounts to 75% and 80%
      respectively. No significant difference in the mortality rate between patients
      with embolism (75%) and thrombosis (76%) was found. However a significant
      increase of mortality rate was observed when the surgical intervention became
      afterwards the first 24-hour period. (72% versus 87%). Patients who underwent
      embolectomy or thrombectomy with bowel resection presented an improved survival
      rate compared with patients that underwent only bowel resection. (p = 0.019)
      CONCLUSIONS: Acute mesenteric ischaemia has the characteristics of a highly
      lethal condition and only early recognition and appropriate treatment can reduce
      the potential for a devastating outcome. The reduction of time interval from the
      beginning of symptoms up to the treatment remains the main critical important
      factor.

PMID- 16796011
TI  - Late manifestation of a pseudoaneurysm in the descending thoracic aorta.
AB  - Rupture of the descending aorta following deceleration trauma is a catastrophic
      event because it has a high mortality. Prompt surgical treatment is generally
      considered to be mandatory. However, a few injured patients may leave the
      hospital with an undiagnosed aortic rupture which may give rise to a chronic
      pseudoaneurysm. In this report, a 28-year-old man is presented in whom a
      pseudoaneurysm of the descending thoracic aortic was diagnosed six months after a
      car accident.

PMID- 16796012
TI  - Abdominal aortic aneurysm in a patient presenting with ischemic colitis.
AB  - A 76-year-old man with an abdominal aortic aneurysm (AAA) initially presented
      with ischemic colitis, which was improved by conservative treatment. Preoperative
      assessment by computerized axial tomography scanning and aortography revealed an
      infrarenal type AAA with mural thrombus, stenoses of the right common iliac
      artery and the left internal iliac artery. The patient underwent aortoiliac
      bypass surgery with resection of the stenoses, and reconstruction of the left
      internal iliac artery. No complications including bowel ischemia, were noted
      postoperatively. This case emphasized the potential benefits of the
      extraperitoneal approach to the aorta, reconstruction of both internal iliac
      arteries, and use of prostaglandin E1.

PMID- 16796013
TI  - [A 29-year-old man with Takayasu's arteritis].
AB  - We report on a 29-year-old male patient with collapse and recurrent vertigo.
      Physical examination showed a bruit of the left common carotid artery on
      auscultation and a pulselessness of both arms. The diagnosis of Takayasu's
      arteritis was based on the results of duplex sonography, MRI and angiography
      (stenosis and occlusion of extracranial arteries). Laboratory results did not
      reveal any specific changes. Combined treatment with prednisolone and
      azathioprine was initiated. After 12 days we saw an improvement of
      duplexsonographical and laboratory findings. Takayasu's disease should be
      considered as a differential diagnosis in patients with stenosis and occlusions
      of the aortic arch and its main branches (e.g. pulselessness). MRI is a valuable
      method in detection of wall abnormalities of the aorta, its branches and other
      large arteries.

PMID- 16796014
TI  - Iatrogenic femoropopliteal graft entrapment.

PMID- 16796015
TI  - [Interventional treatment of extracranial carotid stenoses: current status,
      requirements and indications].
AB  - Interventional treatment of extracranial carotid stenoses: current status,
      requirements and indications Around 30000 strokes per year in Germany are caused
      by extracranial obstructions of the carotid arteries. Besides the well
      established surgical endatherectomy, which has been proven to be superior to
      medical treatment alone in randomized multicenter trials, percutaneous treatment
      by balloon angioplasty and stent placement is increasingly performed. This
      consensus paper summarizes the present status of scientific studies and
      controlled treatment registries of carotid angioplasty and stenting and yields to
      recommendations regarding its performance and indication. A Medline search was
      done until August 2005 including all randomized comparative studies with clinical
      endpoints and all controlled registries with more than 500 patients included.
      Both completed randomized trials comparing angioplasty and stenting with surgery
      (CAVATAS and SAPPHIRE) did not show a significant difference with respect to
      stroke and death within 30 days. The incidence of this combined endpoint was
      between 3.3 and 6.9% in large multicenter registries. Thus, the current
      endovascular treatment results in a perlinterventional complication rate
      comparable to that which is commonly accepted for vascular surgery. A systematic
      preferably external quality monitoring as well as interdisciplinary cooperation
      most importantly with neurologists is recomendedfor all interventionalists. Based
      on available clinical data, this consensus paper defines recommendation classes I
      or II with a level of evidence B or C depending on symptoms, operative risk
      status of the patient and severity of the underlying stenosis.

PMID- 16796016
TI  - Esophageal impedance monitoring and pathophysiology of gastroesophageal reflux
      disease.
AB  - Up until now, most pathophysiological concepts about gastroesophageal reflux
      derived from measurement of esophageal pH. However, pH monitoring does not detect
      all gastroesophageal reflux events, particularly when little or no acid is
      present in the refluxate. Esophageal impedance measurements made possible to
      detect and quantify all types of reflux i.e. acid, weakly acidic and non-acid
      reflux and to characterize the air-liquid composition of the refluxate. This new
      tool stimulated us to re-examine different aspects of the pathophysiology of
      GERD, but considering all gastroesophageal reflux events rather than only acid
      reflux. In this text we first analyzed gastric factors and the impact of gastric
      emptying on the characteristics of the refluxate. We then foccussed on the
      antirreflux barrier at the gastro-esophageal junction and we analysed the
      patterns of air and liquid reflux during transient lower esophageal sphincter
      relaxations (TLESRs), the most frequent mechanism for reflux in patients with
      GERD. With failure of the antireflux barrier, reflux occurs and we discussed in
      detail the air-liquid patterns, composition and proximal extent of the refluxate
      in normal subjects and patients with GERD both in resting and ambulatory
      conditions. The volume and chemical clearance mechanisms triggered after acid and
      non-acid reflux were characterized. The effect of esophagitis or Barrett's mucosa
      on electrical conductivity and impedance was analyzed as an expression of mucosal
      damage and increased ionic permeability. We discussed the role of non acid and
      gas reflux in esophageal and extraesophageal symptoms in patients with GERD. We
      believe that better understanding of the pathophysiology of GERD can help to
      characterize the relationship between gastroesophageal reflux and symptoms; the
      factors that determine esophageal and extraesophageal mucosal damage and/or
      eventual carcinogenesis related to reflux and to provide a tailored treatment to
      each patient targeting the individual pathophysiological defect.

PMID- 16796017
TI  - The pathophysiological relevance of PAI-1 in cardiovascular diseases and the
      development of monoclonal antibodies as PAI-1 inhibitors.
AB  - Plasminogen activator inhibitor- (PAI-1) is an important component of the
      plasminogen/plasmin system as it is the main inhibitor of tissue-type (t-PA) and
      urokinase-type plasminogen activator (u-PA). Consequently, PAI-1 plays an
      important role in cardiovascular diseases (mainly through inhibition of t-PA) and
      in cell migration and tumor development (mainly through inhibition of u-PA and
      interaction with vitronectin). As a member of the serpin superfamily, PAI-1
      shares important structural properties with other serpins. However, PAI-1 also
      exhibits unique conformational and functional properties. The current review
      provides an overview of the knowledge on PAI-1 gathered since its discovery two
      decades ago. We are discussing (a) its structural properties of the protein and
      their subsequent relation to functional activities, (b) its role in a wide
      variety of (patho)physiological processes and (c) the development of monoclonal
      antibodies aiming to modulate pharmacologically this risk factor.

PMID- 16796018
TI  - [alpha-Oxidation of 3-methyl-branched fatty acids: unraveling of a pathway].
AB  - Peroxisomes have an important role in lipid metabolism e.g. beta-oxidation of
      long and very long chain fatty acids, 2-methyl-branched fatty acids, dicarboxylic
      fatty acids, prostanoids and bile acid intermediates, and synthesis of ether
      lipids. Also the process of alpha-oxidation of 3-methyl-branched fatty acids,
      with phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) as the best known
      example, occurs in peroxisomes. alpha-Oxidation is a process in which fatty acids
      are shortened by one carbon atom. The alpha-oxidation sequence of 3-methyl
      branched fatty acids starts with an activation to the corresponding CoA-ester.
      Subsequently this acyl-CoA-ester undergoes a 2-hydroxylation by the peroxisomal
      phytanoyl-CoA hydroxylase (PAHX). In a third step the peroxisomal 2
      hydroxyphytanoyl-CoA lyase (2-HPCL) splits the carbon carbon bond of the 2
      hydroxy-intermediate into a 2-methyl(n-1)aldehyde and formyl-CoA, which is
      subsequently converted to formate and CO2. Finally the aldehyde is dehydrogenated
      by an aldehyde dehydrogenase to the corresponding acid, which, after its
      conversion to the acyl-CoA ester, can be a substrate for beta-oxidation. 2-HPCL
      is the first thiamine pyrophosphate dependent peroxisomal enzyme in mammals.
      Apart from 2-hydroxy-3-methylacyl-CoAs also 2-hydroxyacyl-CoAs are substrates for
      this enzyme. This indicates that the 2-hydroxy function but not the 3-methyl
      function of acyl-CoA esters is needed for 2-HPCL-activity. Long and very long
      chain 2-hydroxy fatty acids are constituents of brain cerebrosides and
      sulfatides, which mainly occur in myelin.

PMID- 16796019
TI  - Relation between both oxidative and metabolic-osmotic cell damages and initial
      injury severity in bombing casualties.
AB  - BACKGROUND/AIM: We have recently reported the development of oxidative cell
      damages in bombing casualties within a very early period after the initial
      injury. The aim of this study, was to investigate malondialdehyde (MDA), as an
      indicator of lipid peroxidation, and osmolal gap (OG), as a good indicator of
      metabolic cell damages and to assess their relationship with the initial severity
      of the injury in bombing casualties. METHODS: The study included the males (n =
      52), injured during the bombing with the Injury Severity Score (ISS) ranging from
      3 to 66. The whole group of casualties was devided into a group of less severely
      (ISS < 25, n = 24) and a group of severely (ISS > or = 26, n = 28) injured males.
      The uninjured volunteers (n = 10) were the controls. Osmolality, MDA, sodium,
      glucose, urea, creatinine, total bilirubin and total protein levels were measured
      in the venous blood, sampled daily, within a ten-day period. RESULTS: In both
      groups of casualties, MDA and OG levels increased, total protein levels
      decreased, while other parameters were within the control limits. MDA alterations
      correlated with ISS (r = 0.414, p < 0.01), while a statistically significant
      correlation between OG and ISS was not obtained. Interestingly, in spite of some
      differences in MDA and OG trends, at the end of the examined period they were at
      the similar level in both groups. CONCLUSION: The initial oxidative damages of
      the cellular membrane with intracellular metabolic disorders contributed to the
      gradual development of metabolic-osmotic damages of cells, which, consequently
      caused the OG increase. In the bombing casualties, oxidative cell damages were
      dependent on the initial injury severity, while metabolic-osmotic cell damages
      were not.

PMID- 16796020
TI  - [Immunohistochemical analysis of alpha-SMA and GFAP expression in liver stellate
      cells].
AB  - BACKGROUND/AIM: Liver stellate cells play an important role in hepatic fibrosis,
      and its progression to cirrhosis. These cells show immunoreactivity with
      different monoclonal antibodies amongst which the commonest are alpha-smooth
      muscle actin (alpha-SMA) and glial fibrillary acid protein (GFAP). The aim of
      this study was to analyze stellate cell immunoreactivity for alpha-SMA and GFAP
      in tissue sections showing the signs of chronic viral B-hepatitis and compare it
      with those without histopathological changes. METHODS: We included 12 tissue
      samples showing chronic viral B hepatitis in the different stages of fibrosis and
      7 tissue samples showing no histopathological changes. Immunohistochemical
      staining was performed using the streptavidin-biotin method. RESULTS: There was a
      regular presence of alpha-SMA immunoreactivity in tissue sections without
      histopathological changes in the portal tracts and also in liver parenchyma,
      while GFAP expression was noted in the periportal cavity. Tissue sections with
      the signs of chronic viral B hepatitis displayed very strong alpha-SMA expression
      in the portal tracts. A statistical analysis showed a positive correlation
      between the degree of liver fibrosis and alpha-SMA expression along the fibrous
      septa, whereas a negative correlation between the degree of liver fibrosis and
      alpha-SMA expression was present in the portal zone. CONCLUSION: This study
      showed the existance of two different stellate cell subpopulations in liver
      tissue. Differentiation between them was possible on the basis of SMA/GFAP
      expression.

PMID- 16796021
TI  - [Medicamentous abortion with mifepristone and misoprostol in Serbia and
      Montenegro].
AB  - BACKGROUND/AIM: Medicamentous abortion was first introduced in Serbia and
      Montenegro in September 2001. The aim of this study was to assess the efficiency,
      side effects, and acceptability of medicamentous abortion using mifeprostone
      orally (600 mg), and 48 hours later, misoprostol both orally and vaginally in
      different regiments in our population (400 mcg, 600 mcg, 800 mcg). METHODS: A
      total of 235 consecutive women with pregnancies up to 49 days of gestational age
      were assigned to 4 groups according to the different misoprostol regiment (group
      I 400 mcg, group II 600 mcg, group III 800 mcg orally, and group IV 800 mcg both
      orally and vaginally). The principal outcome measure was a successful abortion
      defined as a complete expulsion of intrauterine contents without a need for
      surgical intervention 14 days after the procedure. Other outcome measures were
      the following: drug related effects, and adverse effects related to the abortion
      process. RESULTS: In general, the success rate was 50%, 89.48%, 75% and 92.11% in
      the groups I, II, III, and IV, respectively, as judged by the complete expulsion
      of the intrauterine contents without surgical intervention (t1:4 = 7.005; t2:4 =
      0.3872, t3:4 = 2.9784, p < 0.01). The incidence of adverse effects (vomiting,
      abdominal pain, bleeding, and fever) was low in general, but among our groups it
      occurred mostly with the higher doses of orally applied misoprostol (800 and 600
      mcg). Only one case required urgent curettage for heavy vaginal bleeding, and two
      blood transfusions, as well. No cases of intact pregnancies were recorded in the
      study. CONCLUSION: Our study showed that a mifepristone dose of 600 mg orally,
      and misoprostol 400 mcg orally and 400 mcg vaginally were most effective. Thus, a
      combination of mifepristone and misoprostol for medicamentous abortion should
      take a higher proportion in the termination of early pregnancy in our population.

PMID- 16796023
TI  - [Gender differences in psychopathologic features of agoraphobia with panic
      disorder].
AB  - BACKGROUND/AIM: To examine gender differences in the major psychopathologic
      features in agoraphobia with panic disorder. METHOD: The study was conducted as a
      clinical study. The sample consisted of 119 patients, 32 men (26.9%) and 87 women
      (73.1%) with the basic diagnosis of agoraphobia with panic disorder. All the
      patients were evaluated with the clinical instruments suitable for the assessment
      of various clinical features associated with agoraphobia with panic disorder-
      questionnaires (the Hopkins Symptom Checklist 90, the Panic Appraisal Inventory,
      the Fear Questionnaire, the Beck Anxiety Inventory, and the Beck Depression
      Inventory), and the clinical rating scale (the Panic and Agoraphobia Scale).
      After the data collection, the sample was divided into two groups by the gender.
      Then the groups were compared. RESULTS: There were no differences between the
      genders in the global psychopathologic features (the age at the onset of a
      disorder, duration of a disorder, severity and frequency of panic attacks,
      intensity of general psychiatric symptoms, intensity of general anxiety and
      depression). The women, howerer, reported a subjective perception of a more
      severe agoraphobic avoidance and males were significantly more likely than the
      females to anticipate the serious somatic consequences of panic attacks and worry
      about somatic health. CONCLUSION: There were a few gender specific
      psychopathologic features in patients with agoraphobia with panic disorder, so
      further studies would be necessary to come to a more precise conclusion.

PMID- 16796022
TI  - [Foodborne disease outbreak among soldiers in Nis garrison associated with the
      consumption of coleslaw].
AB  - AIM/BACKGROUND: Large outbreaks of foodborne diseases are always focused by the
      general public who expect experts to rapidly explain both the causes of the
      disease and its growth. This article presents the results of the investigation of
      an outbreak of foodborne disease that has attracted much of the electronic and
      written media attention. METHODS: The data on food items consumed by intoxicated
      and healthy soldiers were obtained by the adapted questionnaire during a field
      investigation performed on November 3-4, 2005. On the same occasion other
      relevant data were also collected. For microbiological investigations stool
      samples from the ill persons were collected, as well as food specimen and swabs
      from the working surfaces and utensils in the kichen where the food had been
      prepared. RESULTS: In the outbreak of foodborne disease, which started on
      November 2, 2005, and terminated on the next day, 103 ill soldiers were
      registered in 7 units scattered over 4 locations in the garrison of Nis. The
      attack rate varied in the affected units from 33 to 338 per thousand, with the
      mean value of 109.7 per thousand. The clinical course of the disease was
      predominantly light including vomiting, diarrhea and fever as the most frequent
      signs of illness. All the affected soldiers were hospitalized, treated with
      symptomatic therapy, and discharged fully recovered. By comparing dishes that had
      been consumed by the ill and the healthy persons before the beginning of the
      outbreak, the greatest statistical significance (p < 0.0001), and the only
      significant relative risk (RR = 3.43) were related to the consumption of the
      coleslaw served for lunch on November 1, 2005. In addition, two control groups
      with the total of 151 persons who had not consumed the coleslaws were identified
      no one of them was affected. An microbiological investigation did not reveal any
      bacterial enteropathogens. CONCLUSION: In the described foodborne disease
      outbreak a causative agent was not identified although coleslaw was the way of
      transmission probably secondarily contaminated by the improper hygiene practice
      during its processing.

PMID- 16796024
TI  - A perspective in epidemiology of suicide in Japan.
AB  - BACKGROUND/AIM: According to the information about deaths from any causes,
      provided by the vital statistics based on the WHO Member Countries mortality and
      morbidity, suicide rate in Japan has been ranking high among the causes of death.
      The number of suicides goes on increasing every year in Japan. In fact, suicide
      rates per 100 000 population have already reached the sixth place among the
      leading causes of death. The aim of this study was to perform epidemiological
      surveys of suicide rates, obtained from the official vital statistics provided by
      the WHO on mortality and morbidity during several past decades in Japan. METHODS:
      Completed suicide data were collected via the vital statistics by the Health,
      Labor and Welfare Ministry (MHLW), Japan and the attempted suicide data were
      extracted from the Annual Report of the Ambulance and Rescue Activities by the
      Fire Prevention and Control Office (FPCO) in Kobe City. The data were examined on
      the basis of social factors including economic trends, gender differences, modus
      operandi of suicide, age group, and physical and mental disorders in suicidal
      behavior and compared to international data. RESULTS: Male suicide rates have
      gradually increased with the four temporal steep risings during the 20th century,
      while those of females have generally reached the stabilisation with no
      fluctuations. Suicides are not always under the influence of economic trends in
      Japan. Suicide rate was the highest in the Akita and Iwate prefectures, known for
      the low population density. Suicide rate increases with aging, reaching a peak in
      the age of 80 and over. The trends of completed suicide rates are elevating by
      males about twice the suicide rate of females which keeps on stable. On the other
      hand, female attempted suicide rates greatly increase from two to five times more
      than those in males which are generally close to the constant. The majority of
      suicides are caused by their physical and/or mental disorders including typical
      depressive states. Suffocations/hangings are the most common methods used to
      commit suicide by both sexes. Utilities and interactions among these several
      components were considered, as well as a perspective of suicidal behavior.
      CONCLUSION: In order to prevent suicide and avoid the worst tragedy for a family,
      it is an essential requirement to collect and analyze any information concerning
      suicide victims.

PMID- 16796025
TI  - [Clinical significance of risk factors control in prevention of chronic renal
      failure progression].

PMID- 16796026
TI  - [Corrosive liquid poisoning--diagnostic and therapeutic dilemmas].

PMID- 16796027
TI  - [Characteristics of immune response in urosepsis].

PMID- 16796028
TI  - [Genomics].

PMID- 16796029
TI  - Soft tissue myoepithelial carcinoma.
AB  - BACKGROUND: Myoepitheliomas are tumors composed predominantly or exclusively of
      myoepithelial cells, usually arising in salivary glands. Cutaneous/soft tissue
      localization is very rare, especially for the malignant myoepitheliomas. CASE
      REPORT: We presented a case of myoepithelial carcinoma involving subcutaneous
      adipose tissue of the left forearm in a woman aged 62 years. The tumor was
      composed of epithelioid and hyaline cell types, arranged in diffuse sheets, nests
      and loose clusters within hyalinized and myxoid matrix. The neoplasm displayed
      high-grade cytologic atypia with some cells having pleomorphic, hyperchromatic
      nuclei, and others showing vesicular nuclei, large nucleoli with scattered
      bizarre giant cells. High mean mitotic count of 7 mitoses/10 high power filds and
      extensive necrosis favoured the diagnosis of malignancy. Immunohistochemical
      staining was positive for cytokeratin (AE1/AE3), epithelial membrane antigen, S
      100 protein, glial fibrillary acidic protein, and vimentin. CONCLUSION:
      Considering the subcutaneous localization, myoepithelial immunophenotype and high
      grade cytologic atypia the neoplasm was classified as a soft-tissue myoepithelial
      carcinoma.

PMID- 16796030
TI  - [Therapeutic approach to progressive Takayasu's arteritis].
AB  - BACKGROUND: Takayasu's arteritis (TA) is a nonspecific autoimmune inflammation
      manifested with systemic large vessel vasculitis which affects predominantly the
      aorta and its main branches. CASE REPORT: We presented a 40-year-old woman with a
      two-year history of the symptoms of compromised circulation in the head, the
      neck, the upper extremities and the right leg, followed by claudications in the
      left leg, numbness in the left hand and stenocardia. Aortic arch angyography
      revealed occlusion of the right subclavian artery stenosis of the right vertebral
      artery (20-30%) and the right iliac artery. Anti-inflammatory agents had no
      satisfactory effect and due to the discase progression first aorto-bifemoral
      bypass grafting, and 10 months later left carotid-axillary bypass grafting were
      performed which led to the restoration of circulation in the lower extremities
      and the left arm. CONCLUSION: This case suggested that a surgical therapy should
      be applied in the cases with progressive Takayasu's arteritis, particularly in
      the absence of a response to the conventional immunosupressive therapy to prevent
      eventual fatal complications.

PMID- 16796031
TI  - [Historical review of the development of war surgery--Part 1].

PMID- 16796032
TI  - Biological disasters of animal origin the role and preparedness of veterinary and
      public health services.

PMID- 16796033
TI  - Biological disasters of animal origin the role and preparedness of veterinary and
      public health services.

PMID- 16796034
TI  - Accidental and intentional animal disease outbreaks: assessing the risk and
      preparing an effective response.
AB  - Intentional animal disease outbreaks are infrequent, if not rare, yet they carry
      the potential for disastrous consequences. Normal but accidental outbreaks are
      not uncommon and they must be handled efficiently, effectively and economically.
      And whatever its origin a disease will then follow its usual epidemiology.
      Therefore, the effectiveness in dealing with the normal, and the practice,
      experience and confidence gained, will significantly aid a country in how it
      minimises the cost of an intentional disease outbreak. The response is what
      determines the financial and economic costs of a disease outbreak. This paper
      provides an overview of the various threats, targets, and possible government
      responses, all of which is then expanded upon in detail in the other papers in
      this issue of the Review.

PMID- 16796035
TI  - The biological and toxin weapons convention.
AB  - The Convention on the Prohibition of the Development, Production, and Stockpiling
      of Bacteriological (Biological) and Toxin Weapons and on their Destruction
      prohibits the development, production, acquisition, transfer, stockpiling and use
      of microbial or other biological agents, or toxins in a manner which has no
      justification for prophylactic, protective or other peaceful purposes. It also
      bans weapons, equipment or means of delivery designed to use such agents or
      toxins for hostile purposes or in armed conflict. It covers biological and toxin
      weapons against humans, animals and plants. This article provides a brief history
      of the Convention and presents an overview of its five Review Conferences; the
      'Ad Hoc Group of Governmental Experts, open to all States Parties, to Identify
      and Examine Potential Verification Measures from a Scientific and Technical
      Standpoint' (usually referred to as VEREX); and efforts to develop a legally
      binding instrument to strengthen the Convention, as well as the annual meetings
      of experts and States Parties which have taken place over the last three years.
      Issues of particular relevance to the World Organisation for Animal Health (OIE)
      are highlighted throughout, demonstrating their longstanding and fruitful
      contributions to ensuring that veterinary science is used only for the benefit of
      mankind.

PMID- 16796036
TI  - Misperceptions in preparing for biological attack: an historical survey.
AB  - Preparing for a biological attack involves analysing and co-ordinating
      information and events in the scientific, political and social arenas. The
      information that must be evaluated is, by definition, incomplete. It is not
      surprising that such interactions have regularly resulted in erroneous
      conclusions and flawed interventions. This historical survey examines instances
      where significant errors have occurred. The author describes several examples in
      each of three broad categories: misapprehensions of the risk of biological
      attack; misappraisals of an anomalous event as a biological attack; and
      misadventures in pre-emptive action to protect against a biological attack. The
      study identifies significant common elements in each of these errors that may be
      useful in avoiding future mistakes. In evaluating the effects of these errors,
      the study concludes that such mistakes often increase the dangers that they seek
      to avoid.

PMID- 16796037
TI  - Public perception and risk communication in regard to bioterrorism against
      animals and plants.
AB  - This paper examines the total international prohibition on the use of disease to
      attack humans, animals and plants, noting that in the past several countries had
      developed programmes for attacks on animals and plants as well as humans. Current
      activities undertaken by intergovernmental organisations - the World Health
      Organization (WHO), Food and Agricultural Organization (FAO) and World
      Organisation for Animal Health (OIE)--to counter the threat of attacks on humans,
      animals and plants are examined. Effective countermeasures to deliberate attacks
      need to be developed in harmony with existing measures to control natural or
      accidental outbreaks of disease. Finally the paper assesses the risk and the
      public perception of it, and considers what risk communication is needed and to
      whom. Clear mandates are needed for the FAO and OIE to be prepared to deal with
      outbreaks of disease, and with contamination of the food supply chain, whether
      accidental or intentional.

PMID- 16796038
TI  - A history of biological disasters of animal origin in North America.
AB  - This paper examines past occurrences in North America relevant to the possibility
      of biological disasters with animal origins. With respect to naturally occurring
      animal disease outbreaks, North America, while not as adversely affected by
      epizootics as other regions, has had its fair share of such outbreaks of both
      'traditional' and emerging animal diseases. The traditional category includes
      such diseases as anthrax, classical swine fever, bluetongue, brucellosis, foot
      and mouth disease, and the family of equine encephalomyelitis viruses. The
      emerging diseases include relatively more recent culprits such as postweaning
      multisystemic wasting syndrome, poultry enteritis mortality syndrome, and newly
      discovered examples of the transmissible spongiform encephalopathies.
      Additionally, several serious diseases of human beings that involve animal
      vectors or reservoirs occur naturally in North America or have emerged in recent
      decades; these include plague, hantavirus, monkeypox, West Nile virus and avian
      derived influenza. At the same time, there have been very few intentional attacks
      on livestock using biological agents and no recorded cases in North America of
      animals intentionally being used to transmit disease to humans. According to the
      historical record, therefore, naturally occurring emerging zoonoses probably
      constitute the greatest threat in terms of biological disasters with animal
      origins. However, some of the general trends in terrorist activity, such as the
      intensification of activities by animal rights extremists against facilities
      undertaking animal research, mean that the possibility of intentional animal
      related biological disasters should not be discounted.

PMID- 16796039
TI  - [The eradication of African swine fever in Brazil, 1978-1984].
AB  - The African swine fever episode in Brazil was due to trade and tourism between
      Spain, Portugal and Brazil, at a time when outbreaks were on the rise in Europe.
      The eradication of the disease, the slaughter of pigs, the elimination of the
      carcasses and the isolation of affected farms were given wide media coverage, and
      had a major socio-economic impact. It was forbidden to raise pigs in garbage
      dumps or to give them feed considered hazardous. Analyses performed in Brazil as
      well as national and international investigations by researchers from reference
      laboratories concluded that the disease had spread from Rio de Janeiro to other
      states, as is stated in official reports. Following emergency measures, a control
      programme was implemented, leading to enhanced quality in the pig farming sector.
      The authors describe epidemiological surveillance of African swine fever,
      classical swine fever and related diseases, biosafety in swine farming, and the
      emergency action plan comprising animal health training for veterinarians and
      social workers. The results of the eradication programme were excellent, despite
      the controversy over compulsory sacrifice in a country with serious social
      problems. In 2004, Brazil was the fourth largest pork producer and exporter, with
      an output of 2.679 million tons and exports of 508,000 tons to international
      markets with very high standards.

PMID- 16796040
TI  - Quantitative risk assessment case study: smuggled meats as disease vectors.
AB  - Outbreaks of foot and mouth disease (FMD), African swine fever (ASF), classical
      swine fever (CSF) and swine vesicular disease (SVD) can cause significant
      economic and social costs and severe trade limitations. A number of commodities
      may be contaminated with these hazards, including meat and meat products derived
      from infected animals. Great Britain (GB) enforces a number of regulations to
      prevent the importation of such pathogens. However, the illegal importation of
      meat provides a route by which controls may be circumvented and pathogens
      imported. This paper discusses a series of risk assessments examining the disease
      risk to the GB livestock population of FMD, CSF, ASF and SVD from the illegal
      importation of any meat product from any region in the world. This paper
      describes the development of a quantitative risk assessment model designed to
      identify the major contributors to this risk, and discusses the challenges posed
      when undertaking such complex risk assessments.

PMID- 16796041
TI  - The illegal introduction of rabbit haemorrhagic disease virus in New Zealand.
AB  - In 1997, a group of pastoral farmers, frustrated by governmental and official
      responses to their problems of rabbit control, introduced and spread the rabbit
      haemorrhagic disease virus in a clandestine operation that succeeded in
      distributing infection over a large area of the South Island before the disease
      was detected by government officials. The government concluded that eradication
      was not technically or economically feasible and the disease was accepted as
      being endemic. The episode highlighted the inadequate decision-making environment
      that existed at the time, now improved by the passage of the Hazardous Substances
      and New Organisms Act. It also highlights the importance of having a
      comprehensive biosecurity detection and response capability, including the
      ability to conduct prompt risk assessments, since preventing entry of biological
      agents may be difficult to achieve in the face of a determined adversary.

PMID- 16796042
TI  - A review of recent unexpected animal disease events in Japan and Korea and the
      follow-up action taken.
AB  - In Japan, the need to improve countermeasures against biological weapons was
      recognised after the Aum Shinrikyo cult attempted to use biological weapons in
      1995. This paper describes how the two relevant ministries in Japan worked
      together to cope with recent disease outbreaks, including cases of classical
      swine fever (CSF) and avian influenza, which evidence suggests might have been
      the result of the deliberate misuse of unauthorised vaccines that had been
      illegally imported. By implementing successful control measures the two
      ministries were able to eradicate all the diseases within very short periods. In
      the past few years, the Republic of Korea has also experienced outbreaks of foot
      and mouth disease, highly pathogenic avian influenza, and CSF, all of which had
      previously been absent (or had been eradicated) in Korea. A review of the
      historical background, major events of the outbreaks and the control measures
      which were implemented are presented here.

PMID- 16796043
TI  - Risk of a rift valley fever epidemic at the haj in Mecca, Saudi Arabia.
AB  - Rift Valley fever (RVF) is a zoonotic disease that affects both humans and
      domestic animals. In humans, it can cause a fatal haemorrhagic fever disease.
      When domestic animals such as sheep, goats, camels and cattle are infected, the
      infection may or may not be accompanied by clinical signs of disease. Both sub
      clinical and clinically affected animals present a hazard as a source of
      infection for humans. The risk of infection is greatest at the time of killing,
      when aerosols of infected blood may be generated, particularly by traditional
      sacrificial slaughtering practices. Every year some 10 million to 15 million
      small ruminants may be slaughtered during the religious festivals at Mecca. Some
      of these animals come from the Arabian Peninsula itself, but most are imported
      across the Red Sea, from countries in East Africa and the Horn of Africa, where
      RVF is known to be enzootic and can be greatly amplified during periods of
      epizootic virus activity. These animals may be transported to and arrive in Mecca
      within the incubation period for the disease. Rift Valley fever is also known to
      occur in the tihama zones of both Saudi Arabia and Yemen.

PMID- 16796044
TI  - Kenya, Mau Mau and bioterrorism.
AB  - The Mau Mau uprising in Kenya was to some extent directed against the European
      settlement of the traditional African livestock and farming areas in what became
      known as the 'White Highlands'. The original population groups were displaced and
      the seasonal grazing ranges for their cattle greatly restricted. When these
      herders grazed their cattle alongside roads in settled areas, there was a strong
      response by the administration and many of the animals were impounded and sold.
      Reprisals for such seizures included the 'hamstringing' of settler cattle, which
      involved cutting the Achilles tendon of a hind limb. This effectively resulted in
      the animals being slaughtered on humane grounds.

PMID- 16796045
TI  - Achievements of the soviet biological weapons programme and implications for the
      future.
AB  - The military-biological complex of the former Union of Soviet Socialist Republics
      was a true Frankenstein's Monster, with a powerful scientific potential--or good
      and for ill. This article examines both the direct scientific results of the twin
      biological weapons (BWs) programmes run by the 'civilian' Biopreparat and by the
      Ministry of Defence (MoD) and the public health benefits that sprang, despite the
      original intent, out of those programmes. The authors will also explore the
      potential for both crop and livestock destruction and for enhanced agricultural
      methods growing out of the parallel Soviet programme under the management of the
      Special Directorate of the Ministry of Agriculture. In the last section of the
      article the authors discuss the situation in the military-biological complex that
      arose after former President Boris Yeltsin's 1992 decree abolishing all research
      and development on offensive BWs. The possibility is considered that expertise,
      technologies and materials from the former Soviet BWs programme have leaked out
      of Russia, because the living standards in Russia remain low and the overwhelming
      majority of scientists have a miserable existence.

PMID- 16796046
TI  - International organisations and their role in helping to protect the worldwide
      community against natural and intentional biological disasters.
AB  - Preventing the spread of disease through international movements is one of the
      key objectives of the World Organisation for Animal Health (OIE). One of the ways
      it seeks to achieve this is by publishing international standards and guidelines
      aimed at, inter alia, preventing the importation of pathogens that are dangerous
      for animals and humans and strengthening Veterinary Services so that they can
      improve their surveillance and response systems. The OIE works in close
      partnership with the Food and Agriculture Organization of the United Nations
      (FAO), and together the two organisations have developed a joint initiative - the
      Global Framework for the Progressive Control of Transboundary Animal Diseases (GF
      TADs). Member Countries of these organisations could increase their capacity to
      manage the risks of disease occurrences, whether natural or deliberately
      introduced, if they would all strictly implement existing OIE international
      standards. Compliance with these standards greatly depends on the political
      willingness of national policy-makers and on a successful transfer of resources
      to developing countries in support of good governance and appropriate policy
      implementation. A United Nations Resolution obliging its Member Countries to
      implement OIE standards could prove invaluable in this respect.

PMID- 16796047
TI  - Distinguishing between natural and unnatural outbreaks of animal diseases.
AB  - An intentional outbreak of disease among livestock, or agricultural crops, will
      share a number of characteristics with those aimed at humans - unexpected pattern
      of disease in season or place, possible explosive incidence, unusual pathogen
      either in itself or of its genetic structure, difficult diagnosis - but there
      will also be notable differences: human cases, if they occur, will be
      coincidental and the major impacts will be delayed and of severe economic
      consequence. An investigative and analytical protocol is proposed for identifying
      such an event. Unless the nature of the event is self-declaring, such
      investigations necessitate a very thorough and careful investigation by a
      dedicated and experienced epidemiologic team. Atthe same time a country should
      take steps in advance of such an event to be prepared and to save time later,
      such as determining possible targets, identifying early warning indicators,
      establishing molecular biologic expertise and reference collections of possible
      pathogens, and preparing a tactical and forensic response.

PMID- 16796048
TI  - [The design and establishment of epidemiological surveillance systems for high
      risk diseases in developed countries].
AB  - In animal pathology, epidemiological surveillance has, over the last two decades,
      gradually become a top priority in developed countries, due to progress made in
      fighting major animal diseases. The management of effective epidemiological
      surveillance networks for high-risk animal diseases in developed countries is
      based on general rules governing epidemiological surveillance networks, but
      involves certain specificities. This article first of all sets out the
      requirements for the optimal functioning of epidemiological surveillance
      networks. It then describes and analyses the qualities expected of high-risk
      animal disease surveillance networks: detection sensitivity and specificity,
      simplicity and adaptability, and good cost efficiency. Finally, it illustrates
      these general concepts via four examples of animal disease epidemiological
      surveillance in developed countries: foot and mouth disease in Europe, West Nile
      virus in the United States of America and France, and bluetongue in France.

PMID- 16796049
TI  - [The design and implementation of effective epidemiological surveillance
      programmes in Sub-Saharan Africa].
AB  - Livestock is one of the main sources of wealth in developing countries. The
      improvement of national herds and of their productivity through controlling the
      main diseases and preventing epizootics is a major objective in these countries.
      The organisation of surveillance systems is indispensable to proper animal health
      management, both nationally and internationally. Therefore, thanks to foreign
      assistance, developing countries have gradually established epidemiological
      surveillance networks, despite unfavourable contexts (poverty, lack of resources
      or infrastructure...). To date, many networks are operating in satisfactory
      manner and produce tangible results. However, further efforts must be made to
      improve the quality of sanitary information produced, its performance and
      sustainability. This article discusses the context and motivations for the
      establishment of epidemiological surveillance networks in developing countries,
      especially in Africa, by describing some of their operational specificities and
      some results. Finally, it presents the example of a Mauritanian animal disease
      epidemiological surveillance network and its role in managing a health crisis.

PMID- 16796050
TI  - Animal disease outbreak control: the use of crisis management tools.
AB  - In this era of globalisation the effective control of animal disease outbreaks
      requires powerful crisis management tools. In the 1990s software packages for
      different sectors of the government and agricultural industry began to be
      developed. In 2004, as a special application for tracking the movement of animals
      and animal products, the European Union developed the Trade Control and Expert
      System (TRACES) on the basis of its predecessor, the ANImal MOvement (ANIMO)
      project. The nationwide use of the ANIMO system by the veterinary authorities in
      Germany marked the beginning of the development in 1993 of a computerised
      national animal disease reporting system--the TierSeuchenNachrichten (TSN)--using
      the ANIMO hardware and software components. In addition to TRACES and TSN the
      third pillar for the management of animal disease outbreaks and crises in Germany
      is the national cattle and swine database--called Herkunftssicherungs- und
      Informationssystem fur Tiere. A high degree of standardisation is necessary when
      integrating the different solutions at all levels of government and with the
      private sector. In this paper, the authors describe the use of these tools on the
      basis of their experience and in relation to what we can do now and what we
      should opt for in the future.

PMID- 16796051
TI  - The national incident management system: a multi-agency approach to emergency
      response in the United States of America.
AB  - This paper outlines the development of a universal incident management system
      across all of government in the United States of America called the National
      Incident Management System. The system has been incorporated into the National
      Response Plan and the procedures of United States Department of Agriculture
      (USDA) agencies, using the United States Forest Service's National Interagency
      Incident Management System as a model. This model has enhanced USDA's
      effectiveness in a wide range of emergencies that might affect American
      agriculture, including natural disasters (e.g. earthquakes, floods, hurricanes,
      pest and disease outbreaks, and wilderness and other types of fires), nuclear and
      conventional events, or the accidental or deliberate introduction of a
      biological, chemical or radiological agent threatening the United States food
      supply, critical infrastructure or economy.

PMID- 16796052
TI  - Making better use of technological advances to meet stakeholder needs.
AB  - Controlling transboundary diseases requires an inclusive and collaborative
      international approach. Decisions should be taken (and seen to be taken) on
      advice from multidisciplinary teams of scientists and representatives from all
      groups significantly affected by the disease (the 'stakeholders'). Changes in
      trade and travel mean that, unless a new model is developed for disease
      prevention, there is a real possibility that transboundary animal diseases will
      become increasingly difficult to control. The traditional government approach of
      dealing almost exclusively with the commercial sector of the livestock industry
      is no longer sufficient, and new ways must be found to include all sectors,
      including 'grey' husbandry (fragmented, disparate groups whose involvement with
      animals may range from the legal and responsible to the unsanctioned and/or
      illegal). The increasing convergence of human and animal health issues makes it
      imperative to make the best possible use of new tools. The particular challenges
      confronting veterinary science are: preventing the introduction of disease,
      rapidly identifying disease and controlling epidemics. This paper focuses on the
      United Kingdom to investigate the inadequacies of current approaches, identify
      needs, offer recommendations and propose a new approach to disease control, which
      emphasises global considerations. The objectives are: better participation across
      the entire sector, better communication, better science and better decision
      making, all of which should lead to better security from disease.

PMID- 16796053
TI  - Disease prevention and preparedness for animal health emergencies in the Middle
      East.
AB  - The animal health situation in the Middle East is particularly unfavourable, as
      this area is exposed to many serious animal diseases. The Middle East is ill
      prepared to institute disease prevention and control measures, due to
      deficiencies at both national and regional levels. Early detection, diagnosis and
      reporting of diseases must become a priority within these countries and effective
      communication should be maintained among them. Regional animal health programmes
      and the support of international institutions are essential to improve
      preparedness for natural or human-caused emergency situations, which can
      seriously affect animal health. Such emergencies can also have significant
      impacts on related public health issues.

PMID- 16796054
TI  - Technology, public policy and control of transboundary livestock diseases in our
      lifetimes.
AB  - There are no technological barriers to eliminating major transboundary livestock
      diseases. 'Elimination' means that diseases no longer threaten livestock in the
      developed world nor the livelihoods of hundreds of millions of small farmers
      elsewhere. The problem is not lack of technology but failure of public policy.
      Developed country policy should actively combat accidental and intentional
      introductions; protect livestock against future advanced biological weapons;
      minimise the economic impacts after introduction by any means; abandon mass
      slaughter as a control tool; engage in disease removal in pursuit of a global
      economic, societal, and environmental agenda; and make appropriate national and
      cooperative investments. This is the moment for policy change because
      transboundary livestock disease elimination now involves powerful government
      ministries outside ministries of agriculture that are concerned about disease
      threats from many sources. Change can acquire support from the public and many
      organisations with shared interests. New policy is needed to change the belief
      that government is solely responsible for excluding disease, responding to
      introductions, and compensating farmers for losses during eradication. Effective
      border control and domestic preparedness programmes depend upon government and
      industry working together with costs falling upon those responsible in the form
      of 'user fees'. Compensation for stock slaughtered during outbreak control should
      be covered by private insurance. Government and industry should share the costs
      of an effective surveillance, diagnostic and response system. Surveillance must
      achieve or approach real-time understanding of the disease situation at all
      stages and in all places and be accessible over the Internet by diverse
      government agencies and stakeholders in-country and abroad. Traditional responses
      must be abandoned because they encourage terrorism. Regulatory approval processes
      must be modernized because they cannot keep up with new technology.

PMID- 16796055
TI  - Use and abuse of mathematical models: an illustration from the 2001 foot and
      mouth disease epidemic in the United Kingdom.
AB  - Foot and mouth disease (FMD) is a major threat, not only to countries whose
      economies rely on agricultural exports, but also to industrialised countries that
      maintain a healthy domestic livestock industry by eliminating major infectious
      diseases from their livestock populations. Traditional methods of controlling
      diseases such as FMD require the rapid detection and slaughter of infected
      animals, and any susceptible animals with which they may have been in contact,
      either directly or indirectly. During the 2001 epidemic of FMD in the United
      Kingdom (UK), this approach was supplemented by a culling policy driven by
      unvalidated predictive models. The epidemic and its control resulted in the death
      of approximately ten million animals, public disgust with the magnitude of the
      slaughter, and political resolve to adopt alternative options, notably including
      vaccination, to control any future epidemics. The UK experience provides a
      salutary warning of how models can be abused in the interests of scientific
      opportunism.

PMID- 16796056
TI  - Factors impacting the acceptance of traceability in the food supply chain in the
      United States of America.
AB  - Global demands for increased food safety and quality assurance programmes,
      increased global competition, changing government rules and regulations,
      political and trade barriers, bioterrorism, and identity preservation
      requirements in global markets are affecting the world's food supply chain. To
      satisfy changing market demands, all suppliers in the food supply chain must
      adaptto these global issues. Total asset visibility must be maintained in
      production, in process, in storage, and in transit.

PMID- 16796057
TI  - [Biological research and security institutes].
AB  - The threat of using biological material for ago-bioterrorist ends has risen in
      recent years, which means that research and diagnostic laboratories, biological
      agent banks and other institutions authorised to carry out scientific activities
      have had to implement biosafety and biosecurity measures to counter the threat,
      while carrying out activities to help prevent and monitor the accidental or
      intentional introduction of exotic animal diseases. This article briefly sets
      outthe basic components of biosafety and biosecurity, as well as recommendations
      on organisational strategies to consider in laboratories that support agro
      bioterrorist surveillance and prevention programs.

PMID- 16796058
TI  - Microbial forensics for natural and intentional incidents of infectious disease
      involving animals.
AB  - Microbial forensics is a relatively new scientific discipline dedicated to
      analysing microbiological evidence from a crime for attribution purposes. It
      builds on traditional microbiology and epidemiology but within a legal framework.
      Important motives for forensic investigations include interdiction of criminals,
      prosecution of justice, and ideally, deterrence of others from committing similar
      acts. Forensic capabilities in animal health should focus on building capacity
      for detection and reporting of increases in infectious disease morbidity and
      mortality among animals that might reflect a covert release of a pathogen.
      Suspicion should be raised when epidemiological patterns are different from those
      expected for the animal population and the pathogen in question. Existing
      capacities for the detection and reporting of epidemic and even endemic diseases
      should be an international priority for the prevention of catastrophic losses in
      animal and potentially in human life. The veterinary community needs to be more
      aware of the legal requirements related to forensic investigations so that
      veterinarians will be prepared to handle evidence properly within their own
      fields.

PMID- 16796059
TI  - Toxins of concern to animals and people.
AB  - Historically veterinarians have diagnosed accidental poisonings and identified
      possible terrorist events before they have come to the attention of public health
      authorities. There are many toxins that pose a threat to both humans and animals
      and the authors examine several of them here, namely, anthrax, tricothecenes,
      staphylococcal enterotoxin B, botulinum toxins, ricin, saxitoxin and
      dinoflagellate toxins. By discussing exposure routes, clinical signs and
      differential diagnoses the authors demonstrate how veterinarians are in a unique
      position to recognise zoonotic diseases, toxin exposure, and acts of
      bioterrorism. The work of veterinarians protects the food supply and contributes
      to human health and this article highlights the importance of coordination and
      communication between veterinarians and physicians. Sharing information is
      critical in confirming diagnoses and, in the case of intentional toxin attacks,
      could also be beneficial in identifying the perpetrators of the crime.

PMID- 16796060
TI  - It is hard to predict the future: the evolving nature of threats and
      vulnerabilities.
AB  - This paper describes the evolving nature of threats and vulnerabilities
      associated with biological disasters with animal origins, and introduces some of
      the pitfalls and opportunities associated with anticipating future threats.
      Evolving threats and vulnerabilities include continued deforestation and
      encroachment on virgin habitats, the effects of globalisation on trade and
      transportation, the increased interdependence and social vulnerability of modern
      society, the commingling of intensive agriculture and traditional farming
      methods, the periodic appearance of pandemics and epizootics, and indications
      that numerous human actors are displaying an increasing interest in and
      capability of using biological agents as weapons. These developments must be
      viewed in the context of various impediments to accurately gauging future
      threats, such as the appearance of new elements that depart from current trends
      and the inherent difficulty in anticipating human, and especially terrorist,
      behaviour. The paper concludes with some broad recommendations for structuring a
      policy response to the threat in an environment of uncertainty about the future.

PMID- 16796061
TI  - International cooperation and preparedness in responding to accidental or
      deliberate biological disasters: lessons and future directions.
AB  - Preparations for international cooperation in response to disease disasters at
      the regional or continental levels are poorly coordinated and cooperation is
      limited, although intergovernmental and international organisations have been
      advocating for years that emergency responses to infectious disease outbreaks
      should be planned for and prepared at the national level. National governments
      are responsible for contingency planning to protect the public; however, this
      responsibility needs to be broadened to encompass regional and international
      approaches. Little public domain information is available on international
      coordinated responses to the deliberate introduction of biological pathogens.
      Terrorist events in the early 21st Century have increased awareness of the risks,
      but solid commitment and internationally resourced initiatives are still lacking.
      The current avian influenza disaster has largely been addressed by the three
      global agencies: Food and Agriculture Organization (FAO), World Organisation for
      Animal Health (OIE) and World Health Organization (WHO), using the underlying
      precepts that shape the Global Framework for the Progressive Control of
      Transboundary Animal Diseases (GF-TADs). The GF-TADs offers a substantial base to
      improve regional epidemiological and environmental information, diagnostic
      networking, trend analysis and intervention against the important epidemic animal
      diseases. International prevention, preparedness and response require
      multidisciplinary teams working in an environment of intergovernmental
      cooperation that encompasses numerous ministries and agencies. This paper focuses
      on known international aspects of collaboration on emergency preparedness and
      addresses the FAO/OIE initiative to strengthen veterinary and public health
      systems involved in controlling and preventing serious health threats.

PMID- 16796062
TI  - Investment in preventing and preparing for biological emergencies and disasters:
      social and economic costs of disasters versus costs of surveillance and response
      preparedness.
AB  - Biological emergencies such as the appearance of an exotic transboundary or
      emerging disease can become disasters. The question that faces Veterinary
      Services in developing countries is how to balance resources dedicated to active
      insurance measures, such as border control, surveillance, working with the
      governments of developing countries, and investing in improving veterinary
      knowledge and tools, with passive measures, such as contingency funds and vaccine
      banks. There is strong evidence that the animal health situation in developed
      countries has improved and is relatively stable. In addition, through trade with
      other countries, developing countries are becoming part of the international
      animal health system, the status of which is improving, though with occasional
      setbacks. However, despite these improvements, the risk of a possible biological
      disaster still remains, and has increased in recent times because of the threat
      of bioterrorism. This paper suggests that a model that combines decision tree
      analysis with epidemiology is required to identify critical points in food chains
      that should be strengthened to reduce the risk of emergencies and prevent
      emergencies from becoming disasters.

PMID- 16796063
TI  - Ensuring good governance to address emerging and re-emerging animal disease
      threats: supporting the veterinary services of developing countries to meet OIE
      international standards on quality.
AB  - As an effect of increased globalisation, animal diseases, in particular those
      transmissible to man, have an immediate global economic and social impact. This
      fact, dramatically illustrated by the current avian influenza epizootic in South
      East Asia and Eastern Europe, clearly demonstrates the crucial importance of the
      national Veterinary Services (VS) for the prevention, early detection and
      response for the efficient control of animal diseases. Complying with this
      mission for the VS presupposes the existence of appropriate governance and
      legislation and of an official system to control their quality and reliability-
      an obvious weakness in many developing and in transition countries. The World
      Organisation for Animal Health (OIE) has therefore developed a project aiming at
      strengthening the VS in those countries facing the greatest animal health threats
      and to bring them into line with OIE international standards already adopted by
      the same countries. Based on the evaluation of the VS and subsequent actions at
      the global, regional and national levels, the project will have a significant
      beneficial impact on the targeted countries as well as the international
      community as a whole, not only in the fields of agriculture, food security and
      production, and food safety, but also for the local and global prevention of
      emerging and re-emerging diseases of veterinary and public health importance. The
      project will be implemented in strong collaboration with the Food and Agriculture
      Organization. The actions proposed must be considered eligible for the concept of
      International Public Good.

PMID- 16796064
TI  - Challenges and options for animal and public health services in the next two
      decades.
AB  - Trade in livestock and livestock products makes up approximately one sixth of
      global agriculture trade. This trade is demand driven, primarily by growing human
      populations, changing economies, and consumer preferences in developing
      countries. Different rates of population growth, economic growth, urbanisation,
      environmental sustainability, and technology transfer will determine which
      countries will reap the greatest benefits. Global trends in demand and supply for
      food, not terrorism, will drive the future of animal and public health service
      delivery. To benefit the greatest number of people and countries, animal and
      public health services should support policies that temper growing disparities
      among rich and poor countries, city and rural populations, and the sexes.
      Economic growth is critical to overcoming disparities between countries and best
      supported by integrated animal health, public health, labour, and foreign
      policies. Opportunities for job growth will be the greatest along the value added
      chain of food production and will require significant investments in science-
      (risk-) based education.

PMID- 16796065
TI  - Biological disasters of animal origin: the role and preparedness of veterinary
      and public health services.

PMID- 16796066
TI  - Positive approaches to responding to discipline in the workplace.

PMID- 16796067
TI  - Don't ask, might not think to tell: communication key to preventing risky drug
      interactions.

PMID- 16796068
TI  - Honoree makes a difference across the globe.

PMID- 16796069
TI  - Nursing and the public policy making process: a primer.

PMID- 16796070
TI  - Nursing's unspoken word.

PMID- 16796071
TI  - Collaboration--the key to success.

PMID- 16796072
TI  - Implantable cardiac arrhythmia devices--Part II: implantable cardioverter
      defibrillators and implantable loop recorders.
AB  - Implantable cardiac devices have become firmly entrenched as important
      therapeutic tools for a variety of cardiac conditions. The second part of this
      two-part review discusses the contemporary use and follow-up of implantable
      cardioverter defibrillators (ICD) and the implantable loop recorder. The ICD has
      become the standard therapy for protecting patients against sudden cardiac death.
      Two recent trials, the Multicenter Automatic Defibrillator Trial II (MADIT II)
      and the Sudden Cardiac Death Heart Failure Trial (SCD-HEFT), demonstrated that
      the ICD is associated with a significant survival benefit for patients with
      reduced ejection fraction (< 0.30-0.35), particularly if heart failure symptoms
      are present. The ICD has an important role in the management of other conditions
      associated with a high risk for sudden death, such as hypertrophic
      cardiomyopathy, long QT syndrome, and Brugada syndrome. The implantable loop
      recorder has become an important diagnostic tool for the patient with unexplained
      syncope.

PMID- 16796073
TI  - Prevention of vascular events in patients with cerebrovascular disease: efficacy
      and appropriate duration of antiplatelet therapy.
AB  - Antiplatelet therapy has shown consistent benefit in the prevention of secondary
      stroke. The paucity of head-to-head studies of different antiplatelet regimens,
      assessment of comparative efficacy, and optimal treatment duration requires
      evaluation and comparison of clinical studies that vary extensively in design and
      follow-up. Evidence for aspirin benefit in secondary stroke prevention is strong,
      but existing studies provide little guidance with regard to treatment duration.
      The efficacy of clopidogrel in secondary event prevention is significantly
      greater than that of aspirin for patients with a history of peripheral artery
      disease, but does not differ from that of aspirin for patients with a history of
      stroke or myocardial infarction. Relative to clopidogrel alone, the addition of
      aspirin to clopidogrel results in increased risk for life-threatening bleeding
      episodes similar in absolute magnitude to the reduction of secondary event risk
      in patients with stroke. Benefits associated with clopidogrel occur early in the
      course of therapy; few data support clopidogrel use for longer than 1 year after
      stroke. Monotherapy with extended-release dipyridamole (ER-DP) provides reduction
      in secondary stroke risk similar to aspirin; however, the combination of aspirin
      plus ER-DP significantly reduces risk relative to either agent alone. Compared
      with placebo and monotherapy with either agent, risk reduction for the aspirin
      plus ER-DP combination continued through 24 months, with no concomitant increase
      in bleeding risk. Additional clinical studies should provide needed comparisons
      of efficacy and guidance with regard to optimal duration of therapy.

PMID- 16796074
TI  - Association of statin therapy and the risk of atrial fibrillation in patients
      with a permanent pacemaker.
AB  - BACKGROUND: Recent studies have shown conflicting results regarding a protective
      effect of statin therapy on atrial fibrillation (AF). HYPOTHESIS: We sought to
      determine whether statins are effective in reducing the risk of developing
      arrhythmia in a cohort of 264 patients (49% women, mean age [+/-standard
      deviation] 71 [+/-12] years) with permanent pacemakers who are at high risk for
      AF. METHODS: All patients who underwent implantation of a permanent pacemaker
      over a 3-year period were eligible for inclusion in the study. We excluded
      patients with AF at implantation, incomplete medication information, or less than
      a yearly follow-up visit. Atrial fibrillation was diagnosed by ECG documentation,
      pacemaker interrogation, and Holter monitoring. Statin treatment was verified
      through a central pharmacy-computerized database (for most patients) or by chart
      review. Of the 264 patients, 36% had coronary artery disease. RESULTS: Atrial
      fibrillation developed in 70 patients (26%) at a median of 359 days post
      pacemaker implantation. The incidence rate for the first occurrence of AF post
      pacemaker implantation among patients treated and not treated with statins was
      10.5 versus 9.8 events per 100 patient-years, respectively (p = 0.81). Even after
      controlling for baseline differences, the hazard ratio (HR) for developing AF
      among statin users did not achieve statistical significance (HR = 0.59 [0.31
      1.12]). CONCLUSIONS: We could not demonstrate that statin therapy had a
      protective effect against the risk of AF in patients implanted with a permanent
      pacemaker. The low prevalence of coronary artery disease in our patients may
      partly explain our results.

PMID- 16796075
TI  - In-hospital mortality among women undergoing contemporary elective percutaneous
      coronary intervention: a reexamination of the gender gap.
AB  - BACKGROUND: Previous studies have indicated that, compared with men, women are at
      increased risk for in-hospital mortality following percutaneous coronary
      intervention (PCI); however, angioplasty techniques and mortality rates have
      improved since earlier reports. HYPOTHESIS: We sought to reevaluate and explore
      further the relationship between gender and angioplasty outcomes in contemporary
      "real world" practice. METHODS: The influence of gender and other covariates on
      in-hospital mortality and other adverse events among all patients who underwent
      elective coronary angioplasty in New York State from 1999 to 2001 (n = 106,262)
      was examined. RESULTS: In-hospital mortality rates for elective angioplasty were
      low; however, women demonstrated a two-fold mortality excess compared with men
      (0.6 vs. 0.3%, p < 0.0001). Women were older and more likely than men to
      demonstrate certain higher-risk features (heart failure, class III-IV angina,
      renal failure, vascular disease); however, men were more likely to have depressed
      ejection fraction, prior myocardial infarction, and prior coronary
      revascularization. Using multivariate analysis adjusting for clinical risk
      factors, gender remained an independent predictor of in-hospital mortality at all
      ages. Women were also more likely to experience nonfatal adverse events following
      PCI, including more frequent need for emergency bypass surgery. CONCLUSIONS:
      Despite improvements in angioplasty outcomes with time, women remain at
      significantly higher risk of in-hospital death than men after elective PCI. This
      increased mortality is observed in every age group, even after adjusting for
      other significant comorbidities.

PMID- 16796076
TI  - Insufficient treatment of hypercholesterolemia among patients hospitalized with
      chest pain.
AB  - BACKGROUND: Although morbidity and mortality from coronary artery disease can be
      improved with a variety of pharmacologic interventions, many patients remain
      undertreated. HYPOTHESIS: This study sought to assess whether hospitalization for
      possible coronary artery disease would prompt initiation of appropriate lipid
      lowering therapy. METHODS: This prospective, observational study was conducted on
      consecutive patients with active chest pain admitted to the Emergency Department
      of the hospital for suspected myocardial ischemia. Elevated cholesterol, defined
      as low-density lipoprotein (LDL), was >100 mg/dl with a prior history or a new
      diagnosis of coronary artery disease, or an LDL >130 mg/dl without known coronary
      artery disease. Data were recorded at the time of admission, discharge, and at 4
      month follow-up. RESULTS: Of the patients with hyperlipidemia, 65% men and 55%
      women were on medication at the time of admission (p = 0.30), while at discharge,
      79% men and 60% women were on treatment (p = 0.002), with similar rates of
      treatment at 4-month follow-up (p = 0.030). At discharge, two variables were
      independently associated with patients receiving lipid-lowering therapy: age > or
      =65 years (odds ratio = 2.3; 95% confidence interval 1.2-4.5) and male gender
      (2.7; 15-5.0). CONCLUSIONS: In patients hospitalized with chest pain,
      particularly in women, the initiation of treatment of hyperlipidemia frequently
      does not happen. This oversight represents a lost opportunity for making an
      impact on the health of this population.

PMID- 16796077
TI  - Arterial baroreflex sensitivity is a good predictor of inotropic responses to a
      phosphodiesterase inhibitor in human heart failure.
AB  - BACKGROUND: Experimental study has shown that blunted arterial baroreflex
      function markedly attenuated inotropic responses to a phosphodiesterase inhibitor
      (PDEI) even in normal hearts. However, whether arterial baroreflex function is
      related to the inotropic responsiveness to a PDEI has not been clarified in human
      heart failure (HF). HYPOTHESIS: The goal of this study was to examine the
      relationship between inotropic responses to a PDEI and arterial baroreflex
      sensitivity in human HF. METHODS: Twelve patients with HF were examined, and
      hemodynamic responses to milrinone (12.5, 25, and 50 microg/kg, intravenous
      injection) and arterial baroreflex sensitivity were assessed by pulse interval
      left ventricular (LV) systolic pressure slope using nitroglycerin and
      phenylephrine. RESULTS: Milrinone (25 microg/kg) significantly increased LV
      dP/dt. Arterial baroreflex sensitivity was only one predictor of inotropic
      responses to milrinone by multivariate analysis; a strong positive correlation
      was also found between LV dP/dt and baroreflex sensitivity (y = 6.656X - 3.326, r
      = 0.93, p = 0.000). CONCLUSION: Inotropic effects of milrinone, a PDEI,
      correlated significantly with arterial baroreflex sensitivity, suggesting that
      the more baroreflex function was impaired, the more the inotropic effect of a
      PDEI was depressed in human HF.

PMID- 16796078
TI  - Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic
      subjects.
AB  - BACKGROUND: The metabolic syndrome (MS) is often accompanied by atherogenic
      dyslipidemia, which is characterized by elevated triglycerides (TG), reduced high
      density lipoprotein cholesterol (HDL-C), and elevated numbers of small, dense low
      density lipoprotein (LDL) particles. HYPOTHESIS: It was hypothesized that a
      threshold exists for the circulating TG level needed to produce changes in LDL
      subclass distribution. METHODS: Hypertriglyceridemic (TG > or =300 and <1000
      mg/dl) subjects with the MS were randomly assigned to placebo (n=50) or 130
      mg/day of micronized fenofibrate-coated microgranules (n=96) for 8 weeks.
      RESULTS: In the overall analysis, fenofibrate treatment resulted in significant
      (p < 0.05) changes versus placebo in TG (-36.6%), non-HDL-C (-7.5%), very low
      density lipoprotein-C (-32.7%), LDL-C (15.0%), HDL-C (14.0%), remnant lipoprotein
      C (-35.1%), apolipoprotein B (-6.0%), apolipoprotein A-I (5.3%), and
      apolipoprotein C-III--29.7%). Changes in LDL particle diameter in the fenofibrate
      group were significantly inversely associated with the TG level achieved on
      treatment (p = 0.019). When individually matched for percent change in TG,
      subjects with on-treatment TG < 200 mg/dl, in contrast to those with on-treatment
      values > or =200 mg/dl, had significantly different median responses (p < 0.05)
      in LDL size (0.79 vs. -0.06 nm) and cholesterol carried by small (-35 vs. 21
      mg/dl) and large (31 vs. 11 mg/dl) particles. CONCLUSION: These data support the
      view that a threshold exists below which the TG level must be lowered to produce
      shifts in LDL particle size.

PMID- 16796079
TI  - Implantable cardioverter defibrillator implant-explant-implant case study:
      addressing the psychological adjustment to multiple shocks.
AB  - This case study details the multidisciplinary approach to a patient who underwent
      implantable cardioverter defibrillator (ICD) explantation for psychological
      reasons. The patient was unable to manage the stress associated with multiple
      shocks. He had a class I indication for an ICD but initially refused to undergo
      reimplantation. Treatment included the provision of comprehensive medical,
      nursing, and psychological care, with emphasis on patient autonomy and respect
      for the patient's experience.

PMID- 16796080
TI  - Profiles in cardiology. Adrian Kantrowitz.

PMID- 16796081
TI  - Psychoeducation and expressed emotion by parents of children with learning
      disorders.
AB  - The present study assessed use of a psychoeducation group program on expressed
      emotion, family functioning, and child behavior by parents of children with
      learning disorders. 81 parents of children with learning disorders were randomly
      assigned to a psychoeducation group program (n=46) or to a regular treatment
      group (n=35). A semistructured interview for parental expressed emotion, self
      reports of family functioning, and child behavior were utilized at baseline and
      after an 8-session psychoeducation group program. Parents who attended the
      program differed significantly from parents in the regular treatment group on
      measures of criticism, warmth, and positive remarks, and overall expressed
      emotion, but not on measures of perceived family functioning and child behavior.
      Findings indicate a psychoeducation group program could be effective in helping
      parents to establish a more positive emotional climate in their relationships
      with their children who have learning disorders.

PMID- 16796082
TI  - Excessive self-focused attention and defensiveness among psychiatric patients: a
      vicious cycle?
AB  - The contribution of defensive coping to the phenomenon of excessive self-focused
      attention was studied in 20 depressed or anxious psychiatric outpatients
      comprising the negative affect group, 20 patients with psychotic disorders, and a
      control group of 21 patients of an orthopaedic clinic. Self-focused attention was
      assessed using the Self-reflectiveness and Internal State Awareness subfactors of
      the Private Self-consciousness Scale. In accordance with other research on self
      focused attention, the negative affect group obtained higher scores on the Self
      reflectiveness scale than the control group (t39=2.40, p<.03). To examine the
      relationship between self-focus and defensiveness, Weinberger, Schwartz, and
      Davidson's approach was employed, using median splits of short forms of the
      Taylor Manifest Anxiety Scale and the Marlowe-Crowne scale to differentiate among
      four groups of subjects. The highest self-reflectiveness was found for those
      participants who were high in both defensiveness and anxiety. This group scored
      higher than the nondefensive high anxious group (t30= -2.31, p<.03). The
      heightened self-focused attention might result from automatically instigated
      states of self-focused attention and paradoxical effects of defensive efforts to
      avoid self-focus.

PMID- 16796083
TI  - Locus of control and academic achievement in high school students.
AB  - This study investigated the hypothesized relationship between internal locus of
      control and academic achievement among a sample of 187 students in Grades 8
      through 12 using the Nowicki-Strickland Locus of Control Scale for Children.
      Analysis indicated that students in the higher GPA group reported higher scores
      on internal locus of control.

PMID- 16796084
TI  - Suicide after surgical treatment in patients with epilepsy: a meta-analytic
      investigation.
AB  - Suicide is a major issue in surgically treated epileptic patients. A meta
      analysis was performed comparing suicides in a sample of such patients and in the
      general population. The Index Medicus and the World Health Statistics Annual were
      searched to ascertain the suicide rates in the age groups indicated in the
      studies of epileptic patients for specific years and country. 11 studies were
      selected, comprising 2,425 patients, 24 of whom committed suicide. Data obtained
      for each study were processed together to calculate the mean number of suicides
      per 100,000 individuals with surgically treated epilepsy for each year. This meta
      analysis shows that suicide in patients with epilepsy after surgical treatment is
      more frequent than in the general population. Results are discussed with
      particular attention to possible causative factors.

PMID- 16796085
TI  - Preliminary study of reminiscence therapy on depression and self-esteem in cancer
      patients.
AB  - The present study investigated use of life review, a form of reminiscence, on the
      depression and self-esteem in cancer patients. 15 cancer patients in the
      experimental group participated in individual reminiscence therapy. 21 patients
      in the comparison group received no therapy. All patients were measured on both
      depression and self-esteem scales during two testing periods. Analysis showed
      mean depression scores of the cancer patients decreased and mean self-esteem
      increased significandy after the life-review therapy sessions, while the scores
      of the comparison group did not change. Furthermore, patients' psychological
      states were improved, and they thought their problems had been addressed. These
      results suggest reminiscence therapy can be useful for cancer patients.

PMID- 16796086
TI  - Testing the two-cycle model by different word types.
AB  - The two-cycle model assumes that consonants in words are processed more quickly
      than vowels. This study tested the two-cycle model with different word types
      using a priming task which presented consonants or vowels before the target.
      Analysis showed presenting consonants before the target was beneficial in
      processing the target for the words with the letter compositions of CWC and CVCV.
      In contrast, presenting vowels before the target was beneficial for the words
      with the letter composition of VCVC. The words with the letter composition of
      VCCV showed no difference between the consonant prime and the vowel prime. The
      two-cycle model was not supported across all types of words.

PMID- 16796087
TI  - Preliminary comparison of continuous versus noncontinuous programming and
      attitude toward and recall of advertisements.
AB  - Need for continuity of a television program was assessed with attitude toward and
      recall of advertisements. The program continuity was manipulated experimentally
      by presenting one music video program as Top 10 (continuous) or as Regular
      (discontinuous) format. General attitude toward commercials and the belief in
      advertisement-product realism were investigated through the commercials with
      continuous and discontinuous formats of the same program. Data were gathered from
      undergraduates (23 men and 68 women) whose mean age was 20.2 yr. (SD=2.5).
      Analyses indicated continuity was not related to their attitude towards embedded
      commercials but was associated with their recall. Implications were discussed.

PMID- 16796088
TI  - Loneliness in domestically abused women.
AB  - The qualitative aspects of loneliness in abused women were explored. 80 women,
      victims of domestic abuse who were staying in shelters, were compared with 84
      women from the general population who had no history of abusive relationships. A
      30-item loneliness questionnaire, having five qualitative dimensions of
      loneliness, namely Emotional Distress, Social Inadequacy and Alienation, Growth
      and Discovery, Interpersonal Isolation, and Self-alienation, was utilized to
      compare the loneliness in the two samples. Analysis supported the hypothesis that
      abused women experience loneliness differently from the general population. These
      abused women scored significantly higher on Emotional Distress, Interpersonal
      Isolation, and the Self-alienation subscales.

PMID- 16796089
TI  - Pilot study of hormone replacement therapy and menopausal symptoms, depression,
      and quality of life in Korean climacteric women.
AB  - This cross-sectional survey compared scores on the Menopausal Symptoms Index,
      Depression, and the Quality of Life for 65 Korean climacteric women receiving
      regular hormone replacement therapy (M age=52.8 yr., SD=6.3) and 70 Korean
      climacteric patients not receiving such therapy (M age =51.6 yr., SD=7.1).
      Depression scores were positively correlated with the Menopausal Symptoms Index
      in both groups (r = .58 in the Therapy group and r = .50 in the Control group)
      and negatively correlated with scores for Quality of Life (r = -.48 in the
      Therapy group and r = -.68 in the Control group). Scores on the Menopausal
      Symptoms Index were negatively correlated with ratings of Quality of Life in both
      groups (r = -.53 in the Therapy group and r = -.45 in the Control group). These
      results suggest that hormone replacement therapy is associated with reduced
      Depression scores and higher Quality of Life scores in this sample of Korean
      climacteric women.

PMID- 16796090
TI  - A profile of adolescent alcohol offenders in two rural Midwestern counties.
AB  - Screening tools specifically developed for use with adolescents may be more
      sensitive predictors of relapse or recidivism than self-report inventories
      typically used to screen adults. 70 adolescents in a program for drunk drivers in
      two counties in southeastern Nebraska were given both the CRAFFT and the Alcohol
      Use Disorder Identification Test questionnaires during routine alcohol-dependency
      evaluations. The Michigan Alcoholism Screening Test was also given to 28 subjects
      selected at random. 11 boys and 6 girls did not successfully complete the
      program. Significant correlations obtained for AUDIT scores for both the CRAFFT
      (r69=.65, p<.01) and failure to complete diversion (r69=.23, p<.05). Subjects
      were grouped by age (18 and younger and over 18 years) and by sex. A 2 x 2
      analysis of variance for scores on the AUDIT indicated significant main effects
      for both age (F1,66=4.86, p<.05) and sex (F1.66=5.96, p<.01). MAST and CRAFFT
      scores showed no age or sex differences. The AUDIT might be included in drug and
      alcohol assessments with similar samples of adolescents.

PMID- 16796091
TI  - British and American attitudes toward credit cards.
AB  - American university students owned more than twice as many credit cards as
      British university students. However, scores on a credit card attitude scale
      predicted the number of cards owned by respondents in both countries.

PMID- 16796092
TI  - Sex and sport-related differences in satisfaction among Greek swimmers.
AB  - The purpose was to test the applicability of the Scale of Athlete Satisfaction
      for Greek swimmers and to assess sex and sport-related differences for swimers'
      mean satisfaction. The sample of 351 Greek swimmers comprised 186 males and 165
      females competing in five categories of the National Swimming Championhip in
      Greece. Their mean age was 16 yr. (SD=2; range 13 to 28 years). A confirmatory
      factor analysis supported the factorial validity of the scale. Analysis indicated
      that sex, weekly practice schedule, and sport experience differentiated facets of
      satisfaction among these swimmers. This scale is reliable and valid for measuring
      athletes' satisfaction with individual sports.

PMID- 16796093
TI  - Two cognitions observed in Taijin-Kyofusho and social anxiety symptoms.
AB  - The offensive type is most characteristic in four types of social fear or anxiety
      in Japan, Taijin-kyofusho. This type is characterized by cognitions of other
      offending and avoidance-by-others. The present purpose was to investigate which
      cognition is more important in the pathogenesis of the Offensive type. 220
      undergraduates completed the Other-offending Cognition and the Avoidance-by
      others Cognition Scale, the Interaction Anxiety Scale, and Audience Anxiety
      Scale. Partial correlations, controlling for each cognition in turn, showed a
      significant association only between scores on Social Anxiety Disorder and the
      other-offending cognition. Change in the other-offending cognition may have
      therapeutic importance.

PMID- 16796094
TI  - Positive illusions: positively correlated with subjective well-being, negatively
      correlated with a measure of personal growth.
AB  - Psychologists have long debated the benefits and costs of self-deceptive
      enhancement or positive illusions. Accurate perception of reality is central to
      the definitions of mental health proposed by many personality and clinical
      psychologists, but Taylor and Brown have suggested that having positive illusions
      is associated with increased happiness and satisfaction with life. One
      explanation for the conflicting assertions is that mental health, broadly
      defined, includes both subjective well-being and personal growth, distinguishable
      factors which are differentially related to positive illusions. For this study,
      81 college students completed measures of positive illusions (Balanced Inventory
      of Desirable Responding Self-deceptive Positivity and How I See Myself
      Questionnaire), subjective well-being (Satisfaction With Life Scale and
      Existential Anxiety Scale), and moral reasoning (Defining Issues Test) as an
      index of personal growth. As predicted, positive illusion composite scores were
      positively correlated with scores on the subjective well-being composite (r=.40)
      but negatively correlated with Defining Issues Test scores (r=-.25). The
      quadratic relationship between these measures of positive illusion and subjective
      well-being composites was not significant, indicating no support for an "optimal
      margin of illusion."

PMID- 16796095
TI  - Relations of parental status with alcohol use patterns and attitudes about
      underage drinking.
AB  - In a sample of 143 adults from a population of households in Idaho, significant
      differences in patterns of alcohol use and attitudes about underage drinking were
      related to parental status. Nonparents reported drinking alcohol more frequently
      than parents. Parents were significantly more likely than nonparents to report
      that it is never acceptable for minors to drink alcohol, that minors should not
      be allowed to drink alcohol at parties with no parents present, and that "sting"
      operations by police are warranted. Surprisingly, nonparents were significantly
      more likely than parents to report stores and bars are not careful enough about
      selling alcohol to minors.

PMID- 16796096
TI  - Subthreshold bipolar traits and suicide risk among undergraduates.
AB  - Data from a sample of 500 undergraduate students showed that depression scores
      were more strongly correlated with suicide risk than were mania scores, uggesting
      that such traits should be routinely screened to evaluate suicide risk.

PMID- 16796097
TI  - Repeated questioning for order of events: disparate effects following logical
      versus random presentation.
AB  - In the present study, 72 college-age participants from an introductory psychology
      course viewed a series of 20 pictures depicting events surrounding a routine
      activity, i.e., eating at a cafeteria; these pictures were presented either in a
      logical order. e.g., enter cafeteria, pick up tray, stand in line, and select
      food, or in a random order. Three successive tests of free reconstruction of
      order indicated disparate effects of these conditions; random presentation
      produced significant forgetting of order information across tests, whereas
      logical presentation produced no change in performance across tests. Whereas
      randomly presented stimuli produced both reliable intertest recovery
      (reminiscence) and forgetting, neither result was observed following logical
      presentation. The implications of these data for eyewitness testimony for general
      theories of hypermnesia are discussed.

PMID- 16796098
TI  - Teachers' self-efficacy and organizational citizenship behaviors.
AB  - The aim of the study was to investigate the relationship between teachers'
      instructional efficacy and their organizational citizenship behavior.
      Questionnaires were sent to a sample of 1,100 French Canadian high school
      teachers. A response rate of 44.36% was obtained (279 women and 208 men whose
      mean age was 40.4 yr.) Teachers' instructional efficacy was assessed with a
      French Canadian version of the Teacher Efficacy Scale and organizational
      citizenship behavior was assessed with a questionnaire constructed for the study.
      Analysis yielded positive and significant correlations (rs ranging from .19 and
      .34, p<.01) between teachers' personal teaching efficacy and organizational
      citizenship behaviors such as altruism, courtesy, conscientiousness, and civic
      virtue. General teaching efficacy was only related to sportsmanship (r=.15, p
      <.01). So the predictions were partially supported by the results.

PMID- 16796099
TI  - Evidence of computerphobia in Nigerian education majors.
AB  - The 20-item Computer Anxiety Scale was administered to a Nigerian sample of 162
      undergraduates in education (53 men and 109 women). Analysis indicated that the
      construct of computer anxiety appears to be invariant with respect to sex, year
      of study, or group (science/nonscience). In addition, a high prevalence of
      computer anxiety was observed as about two-thirds of the participants had
      computer anxiety scores exceeding 60 with a mean score of 65.3 (SD= 16.6).

PMID- 16796100
TI  - Validity of self-efficacy scale scores for a Spanish sample.
AB  - This study analyzed the validity of the Sherer, et al. Self-efficacy Scale for a
      Spanish sample of 555 subjects, 257 men and 298 women. 415 were from the general
      population; 34 schizophrenics and 45 with eating disorders were from a clinic,
      plus 61 drug addicts from two centers. All met DSM-IV-R criteria. The Eysenck
      Personality Questionnaire, State-Trait Anxiety Inventory, Assertiveness
      Inventory, and the Self-control Questionnaire were administered. The reliability
      for total scores, general factor were high even when social self-efficacy was
      low. A bidimensional factor structure seemed more acceptable. The Self-efficacy
      scale scores correlated with those on the Self-control Questionnaire and the
      Assertiveness Inventory. Extraversion scores on the Sincerity dimension of the
      Eysenck Personality Questionnaire correlated with scores on the State-Trait
      Anxiety Inventory and Eysenck's Neuroticism and Psychoticism scales. Significant
      mean differences appeared between the general population group and the three
      clinical groups. These analyses support the usefulness of the scale for clinical
      practice and research with Spanish samples.

PMID- 16796101
TI  - Associations of students' self-reports of their teachers' verbal aggression,
      intrinsic motivation, and perceptions of reasons for discipline in Greek physical
      education classes.
AB  - In this study were examined associations among physical education teachers'
      verbal aggressiveness as perceived by students and students' intrinsic motivation
      and reasons for discipline. The sample consisted of 265 Greek adolescent students
      who completed four questionnaires, the Verbal Aggressiveness Scale, the Lesson
      Satisfaction Scale, the Reasons for Discipline Scale, and the Intrinsic
      Motivation Inventory during physical education classes. Analysis indicated
      significant positive correlations among students' perceptions of teachers' verbal
      aggressiveness with pressure/ tension, external reasons, introjected reasons, no
      reasons, and self-responsibility. Significant negative correlations were noted
      for students' perceptions of teachers' verbal aggression with lesson
      satisfaction, enjoyment/interest, competence, effort/importance, intrinsic
      reasons, and caring. Differences between the two sexes were observed in their
      perceptions of teachers' verbal aggressiveness, intrinsic motivation, and reasons
      for discipline. Findings and implications for teachers' type of communication
      were also discussed and suggestions for research made.

PMID- 16796102
TI  - Digital access and national character.
AB  - A digital access index was associated with measures of national character (such
      as extraversion and individualism) for 18 industrialized nations, but statistical
      controls for gross domestic product per capita eliminated these associations.

PMID- 16796103
TI  - Need for closure and youths' leisure time preferences.
AB  - The Need for Closure is an individual characteristic which may help explain
      individual differences in engagement in leisure activities. Both a leisure
      engagement inventory and a validated Dutch version of the Need for Closure Scale
      were administered to a convenient sample of 1,035 young adults ages 15 to 24
      years of whom 552 were female. Leisure engagement was hypothesized to differ for
      groups differing in Need for Closure. More specifically, youngsters who score
      high (versus low) on Need for Closure engaged more in structured, cognitively
      effortless, and predictable leisure activities like shopping for fun and going to
      the cinema, while young adults scoring low (versus high) on Need for Closure more
      often participated in unstructured, unpredictable, cognitively effortful or
      challenging leisure activities like going to a party, a pub, or a pop concert,
      idly lazing away, visiting or hosting friends, attending an evening class and
      playing computer games.

PMID- 16796104
TI  - Children and adolescents with idiopathic scoliosis: emotional reactions, coping
      mechanisms, and self-esteem.
AB  - The main aim of the present study was to investigate the relationship among
      emotional responses of children and adolescents with idiopathic scoliosis towards
      their physical state, the coping mechanisms they used, and their self-esteem and
      the treatment condition of their disorder, i.e., the use of a brace or not. 82
      children and adolescents ages 7 to 17 years who were attending an outpatient
      scoliosis clinic were administered two questionnaires; one evaluated emotional
      and behavioral factors linked to coping with stressful situations, and the second
      assessed self-esteem. Analysis showed that, after adjusting for emotion-focused
      coping, general self-esteem, and age, the effect of the use of brace as a
      treatment technique on the participants' emotional reactions was not significant.

PMID- 16796105
TI  - Role function and job satisfaction of school psychologists practicing in an
      expanded role model.
AB  - School psychologists are typically itinerant among multiple schools and often
      spend up to two-thirds of their time on assessment activities related to students
      with disabilities and special education programs. School psychologists in
      delivery of an expanded role service model are assigned to a single school and
      provide more consultation and intervention services. 97 school psychologists
      assigned to an expanded role in a single southeastern urban school district were
      surveyed on their job roles and job satisfaction. The majority were satisfied or
      very satisfied with their jobs, particularly with engaging in activities that
      were of service to others and staying involved in a variety of job activities.
      School psychologists wanted to spend less time in assessment, multidisciplinary
      team meetings, and administrative duties. The discrepancy between the desired and
      actual amount of time spent in multidisciplinary meetings was negatively related
      to job satisfaction. Psychologists wanted to spend more time in direct and
      indirect intervention, professional development, and networking.

PMID- 16796106
TI  - Fragment difficulty in priming on word-completion tests.
AB  - Word-fragment completion is a frequently used test in implicit memory research.
      In this test priming is the relevant variable. Priming is obtained by subtracting
      the proportion of nonstudied word fragments correctly completed (called
      "completion difficulty baseline") from the studied word fragments correctly
      completed. Since completion difficulty can spuriously vary greatly between
      experimental conditions, its effect on magnitude of priming is studied. Normative
      frequency of occurrence of target words was considered because their influence
      over performance is known. In an experiment using a word-fragment completion
      test, participants' completion of fragments at three levels of completion
      difficulty and two levels of frequency was tested. Analysis showed that
      completion difficulty had a significant effect on global priming. The priming
      magnitude was higher for Difficult and Moderately Difficult fragments than for
      Easy ones. An interaction between fragment difficulty and normative word
      frequency was observed. When the fragments were easy to complete, the expected
      effect of higher priming for low-frequency words than for high-frequency words
      was not observed.

PMID- 16796107
TI  - Toward measurement of social exchange resources: reciprocal contributions and
      receipts.
AB  - This study investigates development of measures for the social resources which
      may be exchanged in working relationships, such as between supervisors and
      subordinates or between employees and work group peers. Items designed to measure
      social resource categories were administered to a heterogeneous sample of 260
      employees from diverse organizations. This sample was fairly evenly divided by
      sex, age, job type, and employment tenure. Analysis showed both contribution and
      receipt of social resources can be distinctly measured for four different
      categories (information, respect, liking, and effort).

PMID- 16796108
TI  - Construct and concurrent validity of the Korean Career Indecision Inventory.
AB  - Construct and concurrent validity of the Korean Career Indecision Inventory were
      examined. Data were collected from 238 South Korean college students. A
      confirmatory factor analysis supported the original five-factor model. As
      hypothesized, scores were significantly correlated with various variables such as
      scores on the Korean versions of the Career Decision Scale (r =.49), the
      Vocational Identity Scale in My Vocational Situation (r=-.63), the Career
      Decision-making Self-efficacy Scale (r=-.47), and Negative Affectivity (r=.37).
      These results support construct validity inventory. Students who indicated they
      were undecided about their careers had significantly higher scores than those who
      indicated they had decided on a career, supporting concurrent validity.
      Implications and limitations are discussed.

PMID- 16796109
TI  - Career pathfinders: a qualitative study of career development.
AB  - This paper examined the perceptions of career path and issues of MBA students in
      response to Lore's The Pathfinder, a comprehensive career-planning model. Using
      internet discussion boards, an interactive dialogue was mentioned by participants
      in response to the components of Lore's model. The sample consisted of 50 fully
      employed MBA students enrolled in a course on self-assessment and career
      planning. A total of 1,781 separate postings were made and analyzed, using
      inductive analysis derived from discussion threads based on Lore's categories:
      comments on Lore's Pathfinder model, living a life you love (what's the holdup,
      career fantasies, work and family issues, and career selection), how to get there
      from here (commitment and future from the present), and designing your future
      career. Findings indicated several interesting trends in the career planning of
      current MBA students, particularly the importance of self or self-reflective
      observations in real time as students who are also fully employed formulate
      career plans. Implications for psychologists and career counselors, career
      development models, and suggestions for research are presented.

PMID- 16796110
TI  - Emotional and sexual jealousy as a function of sex and sexual orientation in a
      Brazilian sample.
AB  - The goal of the present study was to compare the relative distress of homosexual
      and heterosexual Brazilian men and women on scenarios in which they imagined
      their partners sexually or emotionally involved with another person, using a
      forced-choice paradigm and continuous measures. Participants were 68 heterosexual
      men, 72 heterosexual women, 42 homosexual men, and 35 homosexual women. On the
      forced-choice questions heterosexual men (39 on one question and 37 on the other)
      were more upset than their female counterparts (21 on one question and 15 on the
      other) by scenarios of sexual infidelity than those of emotional infidelity. On
      questions using continuous measures no significant difference was found between
      pleasurable sex and attachment scenarios for heterosexual women or heterosexual
      men. On the highly upsetting scenarios heterosexual men discriminated between
      flirting and both pleasurable sex and attachment scenarios, being less disturbed
      by the former. In contrast, heterosexual women were equally distressed by the
      three scenarios. Scores for the homosexual men and homosexual women fell in
      between those of the heterosexual men and heterosexual women and did not show a
      clear cut preference for the sexual infidelity or the emotional alternative on
      the forced-choice paradigm. However, on the continuous measures of jealousy
      homosexuals resembled heterosexuals of the opposite sex. There was no evidence
      that jealousy would be less intense among homosexuals although reproductive
      outcomes were not at risk.

PMID- 16796111
TI  - Relationship between duration of HIV disease and diagnostic history.
AB  - The duration of being infected with HIV, i.e., chronicity, is a unique factor
      that can affect coping and psychological outcomes. In a secondary data analysis,
      50 HIV-positive adults between 30 and 57 years were administered the Centers for
      Epidemiological Studies-Depression scale, the UCLA Loneliness Scale-Revised, and
      the HIV Stigma Scale, along with questions about their diagnostic history.
      Analysis indicated that those diagnosed longer with HIV reported ruminating less
      on the events leading up to their diagnosis (r=-.36), reported less trauma by
      their diagnosis initially (r=-.31), and reported fewer depressive symptoms (r=
      .30). Implications for addressing chronicity in research are posited.

PMID- 16796112
TI  - Reliability and validity of a measure of emotional intelligence in an Iranian
      sample.
AB  - The purpose of this study was to investigate the reliability and validity of the
      Mayer-Salovey-Caruso Emotional Intelligence Test, Version 2.0, in the Iranian
      culture. The sample included 353 students (168 male, 185 female) from senior high
      schools in Shiraz, ranging in age between 16 and 18 years (M=17.1), SD=.5), and
      394 students (113 male, 281 female) from Shiraz University, ranging in age
      between 19 and 25 years (M=21.3, SD= 1.7). The subscale-total score correlations
      were in the upper fifties. Cronbach coefficient alpha was .86 for the full score
      and ranged from .58 to .86 for the 4 subscales of the test. The factor analysis
      supported 1- and 2-factor solutions of the emotional intelligence domain. The
      results generally supported the reliability of the test at the total score level
      for research in the Iranian culture.

PMID- 16796113
TI  - Can business and economics students perform elementary arithmetic?
AB  - Business and economics majors (N=146) were tested on the D'Amore Test of
      Elementary Arithmetic, which employs third-grade test items from 1932. Only 40%
      of the subjects passed the test by answering 10 out of 10 items correctly. Self
      predicted scores were a good predictor of actual scores, but performance was not
      associated with demographic variables, grades in calculus courses, liking for
      science or computers, or mathematics anxiety. Scores decreased over the subjects'
      initial years on campus. The hardest test item, with an error rate of 23%,
      required the subject to evaluate (36 x 7) + (33 x 7). The results are similar to
      those of Standing in 2006, despite methodological changes intended to maximize
      performance.

PMID- 16796114
TI  - Achievement goals and engagement in individual and collective learning
      activities.
AB  - The relationship between achievement goals and individual and collective learning
      activities was examined for 290 university students who completed two
      questionnaires. One assessed three achievement goals-a mastery goal and two
      performance goals, namely, approval seeking and advancing. The other
      questionnaire measured how actively students report engaging in individual and
      collective learning activities. Regression analyses showed that the adoption of
      mastery goals was associated with active engagement in both individual and
      collective learning, while adoption of a performance goal of approval seeking was
      associated with passive engagement in individual learning activities. These
      results are discussed in relation to their theoretical implications and in regard
      to the possible moderating effect of protecting self-worth.

PMID- 16796115
TI  - Profiles of change in self-constructions among early- and later-bereaved widows.
AB  - The portrayal of the construct self was formulated using the protocols of 12
      bereaved widows ranging in age from 56 to 82 years of age at the time of the
      interview. Each widow was interviewed every two to three weeks using a structured
      interview together with a self-report scale. They were asked to revisit their
      expeiences of coping with the death of their husbands in their efforts to adapt
      to life without their husbands and assess the nature of their coping actions.
      Using Lazarus and Folkman's 1986 coping scale enabled the delineation of three
      coping action modes or solutions of "moving away," "moving against," "moving
      toward," self and others in terms of Horney's early work. Analysis of the
      profiles using these coping action modes suggested qualities of restructuring of
      the self among the 12 bereaved widows. Some simple observations were made about
      the importance of research on self-constructions and the potential for the use of
      internal dialogues in grief work.

PMID- 16796116
TI  - A unidimensional measure of Hong's psychological reactance scale.
AB  - Research using Hong's Psychological Reactance Scale has been fraught with
      methodological concerns. Researchers have been unable to find a stable, a nd
      replicable factor structure. Here, results suggested t hat Hong's Psychological
      Reactance Scale is a unidimensional one with an average alpha of .74 (SD=.46).
      This value was attained by first analyzing correlation matrices reproduced from
      three reports on Hong's Psychological Reactance Scale and then verifying this new
      factor structure with original data. Tests for internal consistency supported a 1
      factor solution. Tests for external consistency supported prior findings in
      relation to Psychological Reactance and offer evidence that the 1-factor solution
      is externally valid. While the authors contend that a 1-factor solution is
      appropriate, further testing is needed for external consistency and refinement of
      the measure.

PMID- 16796117
TI  - The moral judgment test: comments on Villegas de Posada's critique.
AB  - The Moral Judgment Test is an operationalization of Kohlberg's notion of moral
      judgment competence and Piaget's two-aspect model of behavior and thus differs
      from tests of preferred moral orientations and Kohlberg's own Stage measurement.
      As this best presents counter-arguments to be rated in regard to their moral
      quality, it is a difficult task for many, and the C score reflects the
      respondents' competence to cope with the task. Validation studies of 27 language
      versions and thirty years of use in research and evaluation studies have
      indicated the Moral Judgment Test is valid and useful for assessing affective and
      cognitive aspects of moral behavior for research and evaluation.

PMID- 16796118
TI  - Work organization, economic inequality, and depression among nursing assistants:
      a multilevel modeling approach.
AB  - To investigate the relationships among the nursing home work environment,
      emotional strain, and depression in Nursing Assistants in Ohio and West Virginia,
      this cross-sectional study was conducted with 395 Nurse Assistants in 49 nursing
      homes in Ohio and West Virginia. Organizational attributes were measured
      independently at the individual and organizational levels. Multilevel modeling
      techniques were used to analyze the data. Our methods examined nursing home
      organizational structure (ownership type, managerial style), and work
      organization (emotional strain) was examined in relation to the prevalence of
      depression among nursing assistants. Our findings suggest workplace emotional
      strain and age are associated with increased odds of depression. Implications of
      our work include that work in nursing homes for the environment it fosters has a
      strong effect on emotional strain and depression among Nursing Assistants.

PMID- 16796119
TI  - Astrological signs and personality in Kuwaitis and Americans.
AB  - Samples of Kuwaiti (N=460) and American (N=273) undergraduates responded to six
      personality questionnaires to assess optimism, pessimism, suicidal ideation, ego
      grasping, death anxiety, general anxiety, and obssessive-compulsiveness. Each
      participant was assigned to the astrological sign associated with date of birth.
      One-way analyses of variance yielded nonsignificant F ratios for all the seven
      scales in both Kuwaiti and American samples, except for anxiety scores among
      Americans. It was concluded that there was little support for an association
      between astrological sun signs and scores on the present personality scales.

PMID- 16796120
TI  - Educational attainment, intelligence, interstate migration, and suicide rates in
      the United States: rejoinder to Abel and Kruger (2005).
AB  - Abel and Kruger (2005) reported a negative association of educational attainment
      and suicide rate across the United States. Given strong links between
      intelligence and educational attainment, this appears to be inconsistent with
      positive associations of intelligence and suicide rate reported in several other
      geographical studies. However, the apparent inconsistencies may reflect
      interstate migration within the U.S. adult population. Testing this hypothesis
      showed that interstate migration was more strongly related to state suicide rates
      than educational attainment. Thus, the different results obtained by Abel and
      Kruger could reflect migration effects, which for the U.S. might render adult-age
      indicators of educational attainment inappropriate to reflect regional variation
      in intelligence by place of birth.

PMID- 16796121
TI  - [Histological observations on the structural changes in rat lacrimal gland by
      oral administration of lactoferrin].
AB  - The purpose of this study was to clarify the influence of enteric-coated
      lactoferrin (LF) on the secretory function of rat lacrimal secretory gland by
      using light and electron microscope. The results were as follows. 1) Both A and B
      granules were observed in lacrimal gland cells in all groups (control groups of
      young and aged rats, and LF-intake group of aged rat). However, the difference in
      size and distribution of B granules was determined among different groups. 2) In
      the control group of young rat, numerous B granules and well-developed cell
      organelles were observed. On the other hand, a small number of large B granules
      and undeveloped cell organelles were recognized in the control group of aged rat.
      3) In the LF-intake group of aged rat, a large number of large B granules and
      well developed cell organelles showed similar features to those in the control
      group of young rat. 4) Large B granules were supposed to be the secretory
      granules in the final secretory stage. 5) Taken together, it was suggested that
      the enteric-coated lactoferrin (LF) might promote the secretory function of
      lacrimal gland cells in aged rat, resulting in the formation of numerous B
      granules.

PMID- 16796122
TI  - [Anatomical names of skeletal notches--analysis and classification of Latin
      names, and comparison with corresponding Japanese names--].
AB  - For better understanding of the structures comprising the human body and in view
      of possible need for future revision, Latin anatomical names (Nomina Anatomica,
      3rd edition) of the skeletal notches were analyzed and classified, and compared
      with the corresponding Japanese anatomical names. The words following Incisura
      indicated: 1) the structure to which the notch belongs; 2) location of the notch;
      3) the structure of which the notch is a component; 4) the bone or osseous
      structure with which the notch is connected; or 5) non-osseous structure attached
      to the notch. Analysis of Latin names and comparison with Japanese names
      clarified some characteristics of both names and revealed some problems in them.

PMID- 16796123
TI  - Complex intracardiac nervous system.
AB  - The heart is an organ with continuous activity, which must satisfy demands of an
      organism on various conditions. Therefore, heart activity is modulated at many
      levels, including intrinsic regulatory mechanisms, humoral factors and autonomic
      nervous system. The regulation of heart activity by sympathetic and
      parasympathetic nervous system is well known. Accumulated evidence in recent
      decades indicates that intracardiac neurons can also significantly regulate heart
      activity. These neurons are concentrated in multiple heart ganglia. Interactions
      between neurons within intracardiac ganglia together with interconnections
      between individual ganglia provide anatomical and functional basis of complex
      nervous network of the heart. This complex intracardiac nervous system together
      with extracardiac autonomic neurons, innervating heart, provides modulation of
      heart activity during both physiological and pathological conditions. This review
      article summarizes recent knowledge about the role of heart neurons in
      physiological conditions and in etiopathogenesis of selected diseases. Effect of
      pharmacological and surgical interventions on heart neurons is also discussed
      (Fig. 2, Ref. 70).

PMID- 16796124
TI  - Interaction between nitric oxide and prostanoids in the respiratory system.
AB  - BACKGROUND: Prostaglandins and nitric oxide are important mediators of different
      physiological and pathophysiological processes. So far, is not characterized
      clearly their relationship in the conditions of airways hyperreactivity.
      OBJECTIVES: We tried to detect the relationship of interaction NOS-COX in
      conditions of exogenous irritant-induced experimental bronchial hyperreactivity.
      METHODS: Male guinea pigs were used in the experiment. Animals received agent
      that inhibits COX activity--diclofenac in a dose of 10 mg/kg i.m. or direct NO
      donor--molsidomine in a dose of 2 mg/kg i.p. Agents were administered singly (10
      days) or in combination (last 3 days). Then animals were exposed to the toluene
      vapours for two hours over each of three consecutive days to provoke
      hyperreactivity. Then we recorded the reactivity changes to cumulative doses of
      histamine or acetylcholine (10(-8)-10(-3) mol/I). RESULTS: The administration of
      NO donor (10 days) and consecutive COX inhibition (3 days) increased the
      reactivity of both observed preparations in comparison to agents administered
      single. COX inhibition during 10 days and consecutive treatment with NO donor (3
      days) evoked different changes of tracheal smooth muscle and lung tissue smooth
      muscle response but had more beneficial effect on the airways reactivity on the
      whole. CONCLUSION: It is possible to suppose some participation of both followed
      enzymatic systems and theirs interaction in our experimental conditions since
      airways reactivity was affected the by used agents (Fig. 7, Ref. 32).

PMID- 16796125
TI  - Serum magnesium levels in patients with alcoholic and non-alcoholic fatty liver.
AB  - INTRODUCTION: Magnesium is currently a subject of major interest in biology and
      medicine. Magnesium is intimately involved in over 300 enzymatic reactions.
      particularly in processes involving the formation and utilization of ATP. It is
      known that alcoholism is connected with hypomagnesemia. There are also several
      studies describing the disorders of magnesium balance in patients with liver
      diseases. THE AIM OF STUDY: was to investigate the serum magnesium levels in
      patients with liver steatosis. We compared the magnesium levels in patients with
      non-alcoholic and alcoholic fatty liver to estimate if alcoholism is the only
      cause of magnesium disorders or if also liver function disorders play any role in
      the development of magnesium dysbalance in patients with liver steatosis.
      PATIENTS AND METHODS: The studied group consisted of 44 patients with hepatic
      steatosis (25 non-alcoholic and 19 alcoholic). The control group consisted of 57
      healthy subjects. Magnesium levels were assayed by atomic absorption
      spectrometry. RESULTS: Serum magnesium levels were significantly decreased in
      patients with alcoholic (0.67 +/- 0.10 vs 1.02 +/- 0.11 mmol.l(-1)) and also in
      patients with non-alcoholic liver steatosis (0.65 +/- 0.14 vs 1.02 +/- 0.11
      mmol.l(-1)). There were also moderately increased activities of aminotransferases
      and gamma-glutamyltransferase. Plasma triacylglycerols were increased in both
      studied groups. Albumin and prealbumin levels were not changed in comparison to
      the control group. There was a slight increase in plasma levels of immunoglobulin
      A and immunoglobulin G. CONCLUSIONS: The results of our study showed
      hypomagnesemia in both studied groups. Decreased magnesium levels found also in
      patients with non-alcoholic fatty liver suggest that alcoholism cannot be the
      only cause of hypomagnesemia in patients with fatty liver. Hypomagnesemia is not
      only a laboratory symptom of fatty liver but due to its connection with increased
      oxidative stress it might be a risk factor in the progression of fatty liver to
      steatohepatitis (Tab. 3, Ref: 19).

PMID- 16796126
TI  - Vaginosacral colpopexy (VSC)--a new modification of the Mc Call operation using
      vaginosacral ligaments as autologous sliding grafts in posthysterectomy vault
      prolapse.
AB  - OBJECTIVES: The effect of a new modification of the Mc Call operation,
      vaginosacral colpopexy (VSC) was evaluated in the group of 32 patients.
      BACKGROUND: Due to our bad experience with transabdominal lumbosacral colpopexy,
      we tried to find out another solution. METHODS: VSC using the mobilized
      vaginosacral ligaments as sliding grafts (two sutures through the vaginosacral
      ligaments and posterior vaginal wall and the third suture through the uterosacral
      ligaments) for vault prolapse was performed in the group of 32 patients. RESULTS:
      Before operation, the median stage of prolapse was: stage III (range, 0-IV) for
      anterior site; stage II (range, 0-IV) for posterior site; stage I (range, 0-IV)
      of the apical segment, and stage III (range 0-IV) for the most severe segment of
      prolapse. The mean follow-up was 24.5 months (range 9-42 months). There were no
      intraoperative injuries of the bladder, ureter, rectum or small bowel. At the
      final follow-up, the mean stage of the prolapse was following: stage 0 (range, 0
      III) for anterior site, posterior site and the most severe segment of prolapse;
      and stage 0 (range, 0-I) of the apical segment. The total vaginal length (tvl)
      increased significantly (p < 0.001) (Valsalva maneuver) (Vm) and (p < 0.001)
      (Pozzi maneuver) (Pm) from the preoperative mean value of 3.20 +/- 1.18 (Vm) and
      2.70 +/- 0.92 (Pm) to (- 8.33 +/- 0.77) (Vm) and (-7.82 +/- 0.89) (Pm). All 8
      patients with genuine stress incontinence, became continent. 3 of 4 patients with
      potential urinary incontinence required Marshal-Marchetti operation for
      persistent stress incontinence. CONCLUSION: VSC seems to be quick, safe and
      effective procedure for vault prolapse (Tab. 5, Fig. 8, Ref. 31).

PMID- 16796127
TI  - Association of HLA-DPB1 alleles with type I diabetes mellitus in Slovak
      population.
AB  - BACKGROUND: Genes of HLA complex on chromosome 6p21 principally contribute to the
      genetic risk of insulin-dependent diabetes mellitus type I (T1 DM). Associations
      of HLA class II loci allelic variants with T1 DM are well established. Another
      prime candidate, particularly the polymorphic DPB1 gene, has been reported as
      probably contributing to the disorder, but its relative contribution to the
      predisposition to the disease is difficult to assess due to strong linkage
      disequilibrium of HLA alleles. DPB1*0301 and DPB1*0202 have been reported as
      positively and DPB1*0402 as negatively associated alleles in different Caucasoid
      populations (predisposing versus protective alleles, respectively). OBJECTIVES:
      The aim of this study was to establish the occurrence rates of HLA-DPB1 alleles
      in patients suffering from T1 DM and to compare them with those in healthy
      subjects. METHODS: A PCR-SSP method was performed to identify HLA-DPB1 alleles in
      61 patients and 160 healthy controls. The exact Fisher's test was used to
      determine the statistical significance of allele frequency differences between
      patients and control subjects. RESULTS: The analysis of obtained results has
      shown a significantly decreased frequency of DPB1*0402 and slightly increased
      occurrence rates of DPB1*0101 and DPB1*1301, respectively in the investigated
      group of patients. Neither DPB1*0301 nor DPB1*0202 were observed to be over
      represented. CONCLUSIONS: The expected significant decrease in the frequency of
      DPB1*0402 was confirmed, whereas positive associations with DPB1*0301 and
      DPB1*0202, did not prove to be true, respectively (Tab. 1, Ref: 19).

PMID- 16796128
TI  - HLA class II allele frequencies in type 1A diabetes mellitus Slovak patients.
AB  - BACKGROUND: Diabetes mellitus type 1A (DM-1A) is an autoimmune disease in which
      the immune response is directed to pancreatic islet cells. DM-1A occurs in
      genetically predisposed individuals. Among type 1A diabetes associated genes,
      those of the HLA region have the greatest effect. OBJECTIVES: The aim of our
      study was to obtain a comprehensive survey of the HLA-DRB1 and HLA-DQB1 allele
      frequencies in Slovak patients suffering from DM-1A. METHODS: HLA class II
      genotyping was performed on genomic DNA by the PCR-SSP method according to the
      12th Workshop protocol. RESULTS: Our report gives the first presentation of the
      distribution of HLA-DRB1 alleles (including complete DRB1*04 subtypes) and that
      of HLA-DQB1 alleles in the Slovak diabetic patients diagnosed at 0-18 years of
      age. Susceptibility is significantly associated with the alleles DQB1*0302 (OR =
      7.8), DRB1*04 (OR = 4.9), DRB1*0301 (OR = 4.2) and DQB1*02 (OR = 2.2), whereas
      the alleles DQB*0602 (OR = 0.05), DRB1*11 (OR = 0.2), DRB1*15 (OR = 0.2) and
      DQB1*0301 (OR = 0.3) were found to be protective. CONCLUSIONS: Our results,
      consistent with other studies, show increased frequencies of known positively
      associated HLA class II alleles in our type 1A diabetes mellitus patients
      compared to the general (nondiabetic) population. The protective effect of
      previously reported alleles was confirmed as well. Results of our population
      based study serve in clinical practice for the identification of subjects at risk
      of developing DM-1A among the first-degree relatives (Tab. 2, Ref. 12).

PMID- 16796129
TI  - Bioavailability of chalcones.
AB  - Epidemiological evidence suggests that diets rich in fruits and vegetables
      decrease the risk of premature mortality from major clinical conditions,
      including cancer and heart disease. However, it is not yet clear which components
      or combination of components in fruit and vegatables are protective and what is
      their mechanism of action is. Phenolic compounds are important compounds because
      of their contribution to human health and their multiple biological activities.
      Although these compounds are not a panacea for good health, some of their
      beneficialt activities presented in this short review showed their importance and
      their possible usage in the prevention of various diseases (Tab. 1, Fig. 1, Ref:
      42).

PMID- 16796130
TI  - "Different" approach in the operative treatment of congenital clubfoot and its
      results.
AB  - OBJECTIVES: This study compared long-term results of the treatment of idiopathic
      clubfoot at two different University orthopaedic departments. BACKGROUND: The
      treatment of clubfoot is still controversial due to different severity and
      different treatment philosophies. METHODS: Authors retrospectively analyzed a
      group of 273 feet (145 patients) operated on at the Unit of Pediatric
      orthopaedics, Children University Hospital, Bratislava (group A) and the cohort
      of 60 feet (33 patients) operated on at the Ist University Department of
      Orthopaedics, Bratislava (group B), between 1993 and 2002 with follow up period
      from 2 to 11 years (average 72 months). In the group A, McKay procedure was
      indicated in 3 feet, Carroll operation in 35 feet and 160 feet were operated by
      Brockmanns posteromedial release and its modifications (cuboid and metatarsal
      osteotomies). In the group B, McKay procedure was done in 8 feet and 50 feet were
      operated on by Turco/ Zacepin procedure. RESULTS: Recurrences in both groups due
      to the insufficient first step operative reduction and mistakes in after
      treatment were 12%. Satisfactory results (excellent and good) were achieved in
      88% of cases in both groups. CONCLUSION: This study shows, that the results of
      operative treatment of congenital clubfoot from two different departments (using
      different operative techniques but "a la carte philosophy") were comparable in
      most of the cases (Tab. 4, Fig. 3, Ref: 9).

PMID- 16796131
TI  - Surgery of the peripheral nerves.
AB  - OUTCOME: In contrast to the CNS, peripheral nerves have the ability to
      regenerate. This ability has been utilized for a long time in the therapy of
      injuries of peripheral nerves. The aim of the present research was to assess the
      achievements in reconstructive surgery including nerve grafting and peripheral
      nerve suture repair in our clinic. MATERIAL AND METHODS: During the 16-year
      period from 1986 to 2001 we surgically treated 116 patients with peripheral nerve
      lesions. The cases of lesions of the brachial plexus, partial peripheral nerve
      lesions and postoperative revision, as well as the attempts of reconstruction of
      cervical nerves and neurolysis are not included in this work. We analysed the
      results of surgery in our patients who where subjected to treatment of peripheral
      nerves in the arms (95 patients) and legs (21 patients). In 53 patients
      reconstructive surgery was performed by suture repair of peripheral nerve, which
      included treatment of 65 nerves, 10 patients were treated by suture repair of 2
      nerves and repair of 3 nerves in one patient. In 42 patients we reconstructed 45
      peripheral nerves of the hand by autograft. The total number of 42 patients
      compromised 37 males and five females. The average age was 36 years. Double nerve
      reconstruction (ulnar and median) was accomplished in three patients. In the
      remaining 21 patients (14 males and seven females) we performed 21 reconstruction
      operations of 24 injured nerves in the lower extremities, of which 8 operations
      of 9 nerves involved suture repair of peripheral nerves and 13 operations of 15
      nerves were performed using a nerve graft. Their average age was 39.7 years. The
      average period between primary treatment and operation was 6.7 months. In five
      cases the interval exceeded 12 months. Operations were performed by
      microtechnique. All patients were subject to several postoperational tests aimed
      at the estimation of the degree of recovery in sensory and motor adaptation. The
      evaluation was performed according the Seddon classification (1975). Motor
      recovery was evaluated according to a five-point scale and the degree of sensory
      recovery according to a four-point scale. Recovery of grade M4 and S3 (or higher)
      was considered an excellent or very good result and grades M3 and S2 were
      considered a good result. Results corresponding to grades M0-M2 and S0-S1 were
      considered to be insufficient. RESULTS AND CONCLUSION: The results of
      reconstruction operations of peripheral nerves injuries were dependent on the
      patient's age, the period between the injury and operation, the length of the
      autograft, the location of the injury, the type of injured nerve and the
      character of the injury (Fig. 2, Tab. 7, Ref: 15).

PMID- 16796132
TI  - Pedal bypass as urgent surgical revascularisation.
AB  - Pedal bypass (arterial reconstruction with distal anastomosis on the dorsal pedal
      artery (DPA) or in the submalleolar portion of the posterior tibial artery) is
      now considered as a standard method of revascularisation in critically ischaemic
      limb with obliteration of the crural arterial system. While a number of studies
      in large cohorts have proved the success of this method in saving limbs with
      chronic critical ischaemia, only few papers report the pedal bypass as an urgent
      intervention. In this study, the authors describe 3 cases where urgent pedal
      bypass saved the limb threatened by an acute ischaemia (Fig. 3, Ref. 12).

PMID- 16796133
TI  - Cystic renal cell carcinoma--rare clinical finding. Radiographic variations of
      tumor/cyst appearance and further diagnostic work-up.
AB  - OBJECTIVES: To review the cases of cystic renal cell carcinoma and multilocular
      cystic nephroma, point out the radiographic variations and define further
      diagnostic work-up. MATERIALS AND METHODS: Between 2003 and 2005 5 patients with
      suspected cystic renal cell carcinoma were treated surgically (1 pt underwent
      radical nephrectomy, 1 pt laparoscopic cyst decortication, 3 pts ablation), 2
      patients with multilocular cystic nephroma underwent ultrasound guided biopsy.
      RESULTS: Histopathologic examination confirmed cystic renal cell carcinoma (CRCC)
      T1aNOM0 Fuhrman grade 1 in 3 cases, T1bN0M0 Fuhrman grade 2 in one case. One
      patient with suspected tumor inside the cyst wall who underwent laparoscopic cyst
      decortication was excluded (final histology confirmed organized hematoma in the
      cyst wall). Biopsy in 2 patients with multilocular cystic nephroma did not
      confirm the presence of malignant cells. The mean tumor size was 4.2 cm (range
      3.7 to 5.5) for CRCC and 4.7 cm (range 4 to 4.5 cm) for multilocular cystic
      nephroma. All 4 cases of CRCC were clear cell type. CONCLUSION: In conclusion
      according to the data described and from our study, tumor/cyst co-existence
      requires further surgical exploration in group 2, 3, 4. Small cystic renal cell
      carcinomas up to 4 cm in diameter have usually favourable pathology and
      prognosis, which offers the minimally invasive nephron-sparing treatment options
      such as excision, ablation or partial nephrectomy (Fig. 9, Ref. 18).

PMID- 16796134
TI  - History, anatomical nomenclature, comparative anatomy and functions of the
      hippocampal formation.
AB  - The complex structures in the cerebral hemispheres is included under one term,
      the limbic system. Our conception of this system and its special functions rises
      from the comparative neuroanatomical and neurophysiological studies. The
      components of the limbic system are the hippocampus, gyrus parahippocampalis,
      gyrus dentatus, gyrus cinguli, corpus amygdaloideum, nuclei anteriores thalami,
      hypothalamus and gyrus paraterminalis Because of its unique macroscopic and
      microscopic structure, the hippocampus is a conspicuous part of the limbic
      system. During phylogenetic development, the hippocampus developed from a simple
      cortical plate in amphibians into complex three-dimensional convoluted structure
      in mammals. In the last few decades, structures of the limbic system were
      extensively studied. Attention was directed to the physiological functions and
      pathological changes of the hippocampus. Experimental studies proved that the
      hippocampus has a very important role in the process of learning and memory.
      Another important functions of the hippocampus as a part of the limbic system is
      its role in regulation of sexual and emotional behaviour. The term "hippocampal
      formation" is defined as the complex of six structures: gyrus dentatus,
      hippocampus proprius, subiculum proprium, presubiculum, parasubiculum and area
      entorhinalis In this work we attempt to present a brief review of knowledge about
      the hippocampus from the point of view of history, anatomical nomenclature,
      comparative anatomy and functions (Tab. 1, Fig. 2, Ref. 33).

PMID- 16796135
TI  - Dimensions of the triangle of Koch.
AB  - Dimensions of the triangle of Koch varied among the patients. The aim of this
      study was to present the dimensions of the triangle, and to compare the data
      obtained directly by post mortal measurement, using two different methods, and
      indirectly using mathematic formulas. The examination was performed in two
      independent groups consisting of 50 specimens each. Results showed that the mean
      value of area of the triangle of Koch obtained by the first type of post mortal
      measurement was significantly different from the mean value obtained using
      mathematic formulas (261.65 +/- 52.30 mm2 vs 116.74 +/- 13.20 mm2; p=0.00;
      p<0.05). But the mean value of the second type of the measurement was very
      similar to the mathematically obtained data (126.33 +/- 23.71 mm2 vs 116.74 +/-
      13.20 mm2; p=0.278; p>0.05) (Fig. 1, Ref. 10).

PMID- 16796136
TI  - The outcome, working ability and psychic changes after traumatic brain injury.
AB  - INTRODUCTION: Severe traumatic brain injury belongs to diagnoses with
      unfavourable outcome. Almost half of patients die due to this diagnose and many
      survivals remain severely disabled. MATERIAL AND METHODS: In our follow-up file
      we evaluated 52 patients treated at neurosurgical department due to this
      diagnosis. The survivals were subsequently examined in order to determine the
      severity of their objective neurological and cognitive problems. RESULTS:
      Mortality rate in our group reached 56 %. The overall results show cognitive
      disorders (memory disorders, prolonged latency and concentration disorders). Out
      of 92 % of surviving patients, it was neurological impairment that was most
      frequently (65 %) involved. CONCLUSION: Both cognitive disorders and neurological
      impairments are responsible for complicated resocialising including working
      ability which is very low after severe traumatic brain injury--in our group 26 %.
      Major obstacle can be seen in the psychological component of their over-all
      impaired quality of life (Tab. 5, Ref. 6).

PMID- 16796137
TI  - The use of controlled mild hypothermia and immune system status in patients with
      severe brain injury.
AB  - INTRODUCTION: Severe brain injuries pose one of the most important problems on
      our health care because of their high morbidity and mortality. MATERIAL AND
      METHODS: A group of 89 patients after severe brain injury (Glasgow Coma Scale< or
      =8) was included into our research of detecting the changes of immune system
      parameters and their relation to the application of mild hypothermia during the
      early period after the insult. RESULTS: In both of the groups CD3+ and CD4+
      lymphocytic levels decreased significantly after the insult and gradually got to
      normal (p<0.01). The NK cells levels have changed in correlation with the course
      of infection. Immunoglobulin (IgA, IgG) levels were normal or slightly increased.
      IgM levels changes had a close relation to the occurrence of inflammatory
      complications, especially that of pneumonia (p<0.01). The most surprising moment
      in our research was the level of IgE antibodies. They had been high and got even
      higher. They achieved the values typical for atopic reactions or parasitic
      diseases. 77.52 % of the patients with decreased parameters of immune system
      developed extra cranial complications. Immune system disorders appeared more
      frequently in the patients with lower Glasgow Coma Scale after admission
      (p<0.01). The application of mild hypothermia caused an unimportant increase in
      extra cranial complications (p>0.05) having no relation to immunity disorders.
      CONCLUSION: Intensive treatment of intracranial hypertension fundamentally
      affects results of our treatment (Glasgow Outcome Score). The application of
      controlled mild hypothermia doesn't escalate the occurrence of extra cranial
      inflammatory complications after severe brain injury (Tab. 2, Fig. 11, Ref. 15).

PMID- 16796138
TI  - Protein structure and dynamics determined by protein modeling combined with
      spectroscopic techniques.
AB  - Beside of the protein crystals, another attractive option in protein structure
      analysis has recently appeared: computer modeling of the protein structure based
      on homology and similarity with proteins of already known structures. We used the
      combination of computer modeling with spectroscopic techniques, such as steady
      state or time-resolved fluorescence spectroscopy or Raman spectroscopy, and with
      molecular biology techniques. This method could achieve reliable results
      comparable with resolution obtained from crystal structures. Molecular modeling
      of the ATP site within the H4-H5-loop revealed eight amino acids residues, namely
      besides the previously reported amino acids Asp443, Lys480, Lys501, Gly502 and
      Arg544, also Glu446, Phe475 and Gln482, which form the complete ATP recognition
      site. Moreover, we proved that a hydrogen bond between Arg423 and Glu472
      supported the connection of two opposite halves of the ATP-binding pocket.
      Similarly, the conserved residue Pro489 is important for the proper interaction
      of the third and fourth-strands, which both contain residues that take part in
      the ATP-binding (Ref. 34).

PMID- 16796139
TI  - Asserting Bologna Declaration in restructuring of school system at Comenius
      University Medical School Bratislava.
AB  - Asserting Bologna Declaration into university education is a long-term and
      challenging process. New features have to be asserted sensitively in order to
      develop school system and to strengthen the baseline for Declaration. Slovakia
      has started the restructuring of university system and study programs undergoing
      the process of accreditation, however marked support (or reform) for covering the
      costs of university education is missing (expressed as % of gross domestic
      product, Slovakia is still not comparable to other EU countries). At present, not
      satisfactory economic conditions prevent from reaching the content, personal and
      equipment preconditions at universities (Ref. 7).

PMID- 16796140
TI  - The role of medical physics in the scheme of diagnostic and therapeutic processes
      by keeping safety and hygienic regulations.
AB  - According to Standards of European Union the pregradual education should tend
      toward preparation of multidisciplinary working teams that can manage the health
      service using principles of evidence-based medicine, nowadays. The primary aims
      of teaching process is to direct the students to acquire, identify, analyze,
      process and select the reproducible results of physical measurements, to that the
      medical interpretation will be assigned. Our scientific research was directed at
      the existing conditions for professional use of different types of medical
      technique in the surgical and internal disciplines in health service institutions
      in all the regions of Slovakia. It also looked at the possibilities of
      eliminating the various unwanted effects of certain physical factors (Fig. 3,
      Ref. 9).

PMID- 16796141
TI  - The "false friendship" of some medical terms in English-Slovak and Slovak-English
      translation.
AB  - When translating medical texts from English into Slovak or vice versa some terms
      can cause problems because they proved to be "false friends" functioning in both
      languages. Most of these expressions are international words coming from
      classical languages and during the course of time they became different from the
      point of view of their meaning (Tab. 2, Ref. 3).

PMID- 16796142
TI  - Effective management of hospitalized patients--established role of hospitalists
      in the USA.
AB  - OBJECTIVES: Summarize and present benefits of effective management of inpatients
      in US hospitals by hospitalists and discuss the possible implications for
      healthcare system in Slovakia. BACKGROUND: Inpatient or hospital-based internal
      medicine started to separate from traditional office-based medicine about a
      decade ago. Today, hospitalist programs are an integral part of most progressive
      hospitals in the US and the value of such programs is well documented. METHODS:
      Literature review and analysis of Mercy Medical Center-North Iowa hospitalist
      program. RESULTS: Hospitalists improve the quality of care for hospitalized
      patients, use fewer resources and decrease the length of stay. In 1998 there were
      2,000 hospitalists and in 2005 there were more than 15,000 hospitalists in more
      than 1,800 programs throughout the US. It is projected that by the end of the
      decade there will be more than 30,000 hospitalists in the US. Mercy Hospital
      started its hospitalist program in 1999 with one hospitalist and by July 2006 the
      program will expand to six physicians. The average daily census for a hospitalist
      is 20 patients and the average length of stay is 3 days. In 2003, with 874 median
      new admits and consults per year per hospitalist, one hospitalist was able to
      save approximately dollars 400,000/year compared to the traditional internal
      medicine model. CONCLUSION: Hospitalists are the fastest growing specialty in the
      US. In addition to the care of medical illnesses including subspecialty and
      surgical consults, hospitalists also serve as stewards of hospital systems. They
      improve quality, patient safety, efficient use of resources and reduce variation
      in diagnostic and therapeutic approaches (Tab. 2, Fig. 3, Ref. 10).

PMID- 16796143
TI  - Herd protection and herd amplification in cholera.

PMID- 16796144
TI  - A strategy to enhance the global research effort in maternal and child health:
      the Mother-Child International Research Network.

PMID- 16796145
TI  - Defining episodes of diarrhoea: results from a three-country study in Sub-Saharan
      Africa.
AB  - The study was conducted to assess the effect of definition of episode on
      diarrhoeal morbidity and to develop a means of adjusting estimates of morbidity
      for the definition of episode used. This paper reports on a cohort study of 374
      children, aged 9-32 months, in three African countries, which recorded frequency
      and consistency of stool over a seven-month period. Different definitions of
      episode were applied to these data to assess their effect on annualized
      diarrhoeal morbidity. Adjustment factors were then derived that corrected
      morbidity for non-standard definitions of episode. Applying non-standard
      definitions of episode gave estimates of an annualized number of episodes between
      38% and 137% of the internationally-accepted definition. Researchers should be
      encouraged to use the standard definition of episode of diarrhoea and to use
      appropriate field protocols. Where this is not possible, correction factors
      should be applied, particularly where estimates of diarrhoeal morbidity are
      pooled in systematic reviews.

PMID- 16796146
TI  - Under-nutrition affects time to recurrence of gastroenteritis among Aboriginal
      and non-Aboriginal children.
AB  - This study investigated whether under-nutrition affected time to hospitalization
      for recurrence of gastroenteritis in Australian children. Linked hospitalization
      records of all infants, born in 1995 and 1996 in Western Australia, who were
      admitted for gastroenteritis during their first year of life (n=1001), were
      retrieved. A survival frailty model was used for determining the factors
      influencing the recurrent times over the subsequent seven years. Aboriginality
      and under-nutrition were significantly associated with an increased risk of
      recurrence (hazard ratios of 2.59 and 1.28). Hospitalizations due to
      gastroenteritis were common among Aboriginal children who had a higher mean re
      admission rate and much shorter intervals between re-admissions than other
      patients. The proportion of patients with recurrence was also significantly
      higher for Aboriginals (38.5%) than for other patients (14.2%). Gastroenteritis
      remains a serious problem in Aboriginal children. This presents a complex
      challenge to be addressed with public-health principles, political determination
      and commitment, and adequate resources.

PMID- 16796147
TI  - Aetiology of diarrhoea in a birth cohort of children aged 0-2 year(s) in rural
      Mirzapur, Bangladesh.
AB  - The incidence of aetiology-specific diarrhoea and the pathogenicity of infectious
      agents in a birth cohort (n=252) in rural Bangladesh were determined. Stool
      specimens or rectal swabs were collected from diarrhoeal cases over two years and
      routinely on a monthly basis. Stool samples from children with diarrhoea were
      compared with stool samples from children without diarrhoea to calculate rates of
      isolation and pathogenicity of agents. In total, 1750 stool specimens from
      diarrhoea patients and 5679 stool specimens from children without diarrhoea were
      tested. An infectious agent was identified in 58% of the stool specimens from
      diarrhoea patients and 21.6% of the stool specimens from children without
      diarrhoea. The most commonly-isolated pathogens from all specimens were
      enterotoxigenic Escherichia coli (ETEC), enteroadherent E. coli, Shigella,
      Campylobacter jejuni, Giardia, and rotavirus. ETEC (ST and LT-ST toxin),
      enterotoxigenic Bacteroides fragilis, Shigella, and rotavirus were associated
      more with disease than with asymptomatic infections. Aetiology-specific
      infections were associated with acute episodes. The isolated enteropathogens were
      essentially the same as those found in other tropical rural settings.
      Enterotoxigenic B. fragilis was also identified as a pathogen. Ongoing vaccine
      efforts focusing on Shigella, rotavirus, and ETEC would be useful.

PMID- 16796148
TI  - A modified routine analysis of arsenic content in drinking-water in Bangladesh by
      hydride generation-atomic absorption spectrophotometry.
AB  - The high prevalence of elevated levels of arsenic in drinking-water in many
      countries, including Bangladesh, has necessitated the development of reliable and
      rapid methods for the determination of a wide range of arsenic concentrations in
      water. A simple hydride generation-atomic absorption spectrometry (HG-AAS) method
      for the determination of arsenic in the range of microg/L to mg/L concentrations
      in water is reported here. The method showed linearity over concentrations
      ranging from 1 to 30 microg/L, but requires dilution of samples with higher
      concentrations. The detection limit ranged from 0.3 to 0.5 microg/L. Evaluation
      of the method, using internal quality-control (QC) samples (pooled water samples)
      and spiked internal QC samples throughout the study, and Standard Reference
      Material in certain lots, showed good accuracy and precision. Analysis of
      duplicate water samples at another laboratory also showed good agreement. In
      total, 13,286 tubewell water samples from Matlab, a rural area in Bangladesh,
      were analyzed. Thirty-seven percent of the water samples had concentrations below
      50 microg/L, 29% below the WHO guideline value of 10 microg/L, and 17% below 1
      microg/L. The HG-AAS was found to be a precise, sensitive, and reasonably fast
      and simple method for analysis of arsenic concentrations in water samples.

PMID- 16796149
TI  - Impact of zinc deficiency on vibrio cholerae enterotoxin-stimulated water and
      electrolyte transport in animal model.
AB  - The effect of zinc deficiency on the function of the intestine to absorb water
      and electrolytes was studied in animal models, stimulated by Vibrio cholerae
      enterotoxin. Sprague-Dawley rats, used in the study, were divided into four
      groups: Zinc-deficient, ad libitum zinc-fed control, zinc weight-matched control,
      and zinc-deficient acutely-repleted. 14C-labelled polyethylene glycol solution
      was used for measuring the absorption capacity of the small intestine.
      Significantly lower absorption of water and sodium per cm of the intestine was
      observed in the zinc-deficient animals compared to the ad libitum zinc-fed
      control animals (p < 0.01). An improved absorption capacity was equally observed
      in the zinc-deficient acutely-repleted animals and ad libitum zinc-fed control
      group. The zinc-deficient animals showed four times greater cholera toxin-induced
      net secretions of water and sodium compared to the ad libitum zinc-fed group (p <
      0.01), while a 40% reduction was observed in the zinc-deficient acutely-repleted
      group. The results suggest that zinc deficiency is associated with reduced
      absorption of water and electrolytes and increased secretion of the same
      stimulated by cholera toxin.

PMID- 16796150
TI  - Supplementation of fish-oil and soy-oil during pregnancy and psychomotor
      development of infants.
AB  - Supplementation of docosahexaenoic acid (DHA) in infancy improves neuro
      developmental outcomes, but there is limited information about the impact of
      supplementing pregnant mothers with DHA on the development of their infants. In a
      follow-up of a randomized, double-blind controlled trial with 400 pregnant
      mothers, the effects of supplementation of fish-oil or soy-oil (4 g/day) during
      the last trimester of pregnancy on psychomotor development and behaviour of
      infants at 10 months of age (n=249) were assessed. The quality of psychosocial
      stimulation at home (HOME) and nutritional status of the subjects were also
      measured. There were no significant differences in the fish-oil group and soy-oil
      group in any of the developmental (mean +/-SD mental development index: 102.5 +/-
      8.0 vs. 101.5 +/- 7.8, psychomotor development index: 101.7 +/- 10.0 vs. 100.5 +/
      10.1) or behavioural outcomes. It may, therefore, be concluded that
      supplementation of fish-oil during the last trimester of pregnancy does not have
      any added benefit over supplementation of soy-oil on the development or behaviour
      of infants in this population.

PMID- 16796151
TI  - Neurological status of low-risk Vietnamese newborns: a comparison with a British
      newborn cohort.
AB  - A shortened version of the Dubowitz newborn neurological examination, recently
      reassessed in rural Thailand, was applied to a group of 58 Vietnamese newborns.
      The aim was to establish the neurological status of newborns in this population
      for use in further studies and to compare with groups previously studied.
      Compared to the original British cohort, the Vietnamese newborns showed
      significantly lower scores in 10 of 25 items, including several related to
      truncal tone. Evidence was sought of thiamine and long-chain fatty acid
      deficiency as a possible cause for these findings, but no correlation was found
      between the neurological status and the maternal or infant blood levels of these
      nutritional indicators. The findings suggest that the neurological status of low
      risk Vietnamese newborns appears to lie between that of British newborns and
      those ethnic minority Karen newborns in refugee camps on the Thai-Burmese border
      tested previously. Although no specific nutritional cause has been identified in
      the study, the findings may still reflect sub-optimal intake of some important
      nutrients.

PMID- 16796152
TI  - Cryptosporidium and Giardia as determinants for selection of an appropriate
      source of drinking-water in southern Sri Lanka.
AB  - Four different water sources (irrigation canals, small reservoirs, shallow wells,
      and tubewells), used for domestic purposes, in an irrigated area in southern Sri
      Lanka, were tested for Giardia spp. cysts and Cryptosporidium spp. oocysts.
      Identification of these parasites in water sources is important as these are
      increasingly recognized as causative agents of waterborne diarrhoeal disease. All
      the four sources of water were contaminated with cysts and oocysts. The sources
      of surface-water contained a greater number of protozoa compared to tubewells and
      shallow wells (p < 0.05). The results indicate a reduction of high parasite loads
      by natural filtration as the water moves from canals to shallow wells through the
      soil profile. This could present an opportunity to reduce the burden of
      diarrhoeal disease due to protozoa by selecting an appropriate source of drinking
      water and identifying those water sources that require treatment solutions.

PMID- 16796153
TI  - Promoting breastfeeding in Bolivia: do social networks add to the predictive
      value of traditional socioeconomic characteristics?
AB  - This study tested whether the prediction of health-related knowledge (correct
      breastfeeding practices in this case) could be improved by including information
      about the composition of an individual's personal network above and beyond that
      predicted by his/her socioeconomic or demographic characteristics. Few studies
      have tested the predictive value of social networks, especially for population
      based studies, despite an increased use of social networks in the past few years
      in several fields of health research, especially in research relating to
      prevention of HIV/AIDS and design of HIV/AIDS programmes. Promotion of
      breastfeeding practices that enhance child survival is important in Bolivia
      because of high infant morbidity and mortality in the country. Data on a cross
      sectional urban probability sample of 2,354 women and men aged 15-49 years were
      collected from seven urban areas in Bolivia. Model building and the log
      likelihood ratio criteria were used for assessing the significance of variables
      in a logistic model. Results showed that the network variables added
      significantly (p < 0.05 for knowledge of breastfeeding only with no other liquids
      and for knowledge of breastfeeding only with no solids p < 0.01) to the
      predictive power of the socioeconomic variables. These results may also hold for
      other health research areas, increasingly using social network analysis, such as
      that of HIV/AIDS.

PMID- 16796154
TI  - Perceptions of risk and behaviour change for prevention of HIV among married
      women in Mumbai, India.
AB  - Heterosexual transmission accounts for the majority of cases in India, an
      epicentre of the HIV/AIDS pandemic, with increasing rates of infection in married
      women contracting HIV from an infected spouse. Cultural roles and position of
      married women in Indian society render targeted risk-reduction programmes
      difficult. To investigate HIV/AIDS-related knowledge, perceptions, and behaviour
      change among married women in India, an interview-based survey was conducted with
      350 married women in Mumbai, of whom 67% (236) were aware of HIV/AIDS. Although
      59.3% (140) of those aware mentioned indiscriminate sexual activity as increasing
      risk of HIV, only two (41%) in five women perceived HIV as a threat to the
      community; one (12%) in eight perceived personal risk of getting infected as
      high; and only 7.2% (17) reported behaviour change to avoid infection. When
      probed for reasons for not changing behaviour, most women cited their personal
      behaviour of monogamy, not being in an at-risk group, such as commercial sex
      workers, and trust in their husbands. Education programmes among married women
      that enable better understanding of risks are urgently required. Since marriage
      and motherhood are important in the Indian cultural context, male spouses should
      be included in risk-reduction programmes.

PMID- 16796155
TI  - Effect of wealth inequality on chronic under-nutrition in Cambodian children.
AB  - The problems of food insecurity and under-nutrition remain particularly severe in
      countries recovering from recent wars or civil unrest, where improvements in
      economic conditions have tended to benefit the advantaged groups and resulted in
      widespread inequalities in health. Using information on 3235 children aged 0-59
      month(s) included in the 2000 Cambodia Demographic and Health Survey, this study
      examined how economic inequality was associated with inequalities in chronic
      childhood under-nutrition. An under-nourished (stunted) child was defined as
      having his/her height-for-age more than two standard deviations below the
      reference median. Household wealth status was measured by an index based on
      household ownership of durable assets. Binary and multinomial logistic
      regressions were used for estimating the effects of household wealth status on
      moderate and severe stunting. The results indicated that children in the poorest
      20% households were more than twice as likely to suffer from stunting as children
      in the richest 20% households (odds ratio [OR]=2.54; 95% confidence interval [CI]
      1.91-3.39). Adjusting for child's age, sex, birth order, and duration of
      breastfeeding; age of mother at childbirth, body mass index, and education; and
      household access to safe drinking-water, hygienic toilet facility, residence, and
      geographic region made little difference to this effect (OR=2.05; 95% CI 1.28
      3.28). The adjusted effect of wealth status was somewhat stronger on severe
      stunting (relative risk ratio [RRR]=2.26; 95% CI 1.22-4.18) than on moderate
      stunting (RRR=1.89; 95% CI 1.12-3.20). The study concludes that wealth inequality
      is strongly associated with chronic childhood under-nutrition and emphasizes that
      reducing poverty and making services more accessible to the poor will be key to
      improving the health and nutritional status of children in Cambodia.

PMID- 16796156
TI  - District-level religious composition and adoption of sterilization in India.
AB  - This paper examined the influence of religion on the adoption of female
      sterilization, using data from the 1992/93 Indian National Family Health Survey.
      The influence of religion at both individual and district levels was examined,
      and a multi-level modelling methodology was used for assessing community
      variations in the influence of religion on the adoption of sterilization.
      Individual religion was a strong predictor of the decision to adopt
      sterilization, and residence in a district in which more than 20% of the people
      were Muslims significantly lowered the odds of adoption of sterilization. There
      was more variation in the adoption of sterilization between districts for Muslim
      women and women from minority religious groups. The results demonstrate the
      influence of community conservatism on the choice of contraceptive methods and
      point to the mediating effects that community characteristics can have on access
      to sterilization services for women from religious minority sub-groups.

PMID- 16796157
TI  - Standard WHO-ORS versus reduced-osmolarity ORS in the management of cholera
      patients.
AB  - The study compared the safety and efficacy of an oral rehydration salts (ORS)
      solution, containing 75 mmol/L of sodium and glucose each, with the standard
      World Health Organization (WHO)-ORS solution in the management of ongoing fluid
      losses, after initial intravenous rehydration to correct dehydration. The study
      was conducted among patients aged 12-60 years hospitalized with diarrhoea due to
      cholera. One hundred seventy-six patients who were hospitalized with acute
      diarrhoea and signs of severe dehydration were rehydrated intravenously and then
      randomly assigned to receive either standard ORS solution (311 mmol/L) or reduced
      osmolarity ORS solution (245 mmol/L). Intakes and outputs were measured every six
      hours until the cessation of diarrhoea. During maintenance therapy, stool output,
      intake of ORS solution, duration of diarrhoea, and the need for unscheduled
      administration of intravenous fluids were similar in the two treatment groups.
      The type of ORS solution that the patients received did not affect the mean serum
      sodium concentration at 24 hours after randomization and the relative risk of
      development of hyponatraemia. However, patients treated with reduced-osmolarity
      ORS solution had a significantly lower volume of vomiting and significantly
      higher urine output than those treated with standard WHO-ORS solution. Reduced
      osmolarity ORS solution was as efficacious as standard WHO-ORS solution in the
      management of cholera patients. The results indicate that reduced-osmolarity ORS
      solution is also as safe as standard WHO-ORS solution. However, because of the
      limited sample size in the study, the results will have to be confirmed in
      trials, involving a larger number of patients.

PMID- 16796158
TI  - Improving health outcomes through community empowerment: a review of the
      literature.
AB  - This paper reviews the literature on how empowerment can lead to an improvement
      in the health status of an individual, group, or community. There is a broad body
      of literature on empowerment, and this review has been designed to identify
      material, particularly case studies, that can be included within the following
      'empowerment domains': Participation; Community-based organizations; Local
      leadership; Resource mobilization; Asking 'why'; Assessment of problems; Links
      with other people and organizations; Role of outside agents; and Programme
      management. The paper discusses the results of the literature review and provides
      examples, from both developed and developing countries, of how each of the
      'empowerment domains' has led to an improvement in health outcomes. The results
      of the review should be of interest to the planners and practitioners of health,
      population and nutrition programmes that have a particular focus on empowerment.

PMID- 16796159
TI  - Impact of a harm-reduction programme on soft tissue infections among injecting
      drug users of Kolkata, India.

PMID- 16796160
TI  - [Cytohistological and immunohistochemical characteristics of vascular remodelling
      in diseases of the blood vessels].
AB  - INTRODUCTION: Vascular remodelling is an adaptive process involving the
      adjustment of the structure and function of blood vessels to long-term changes in
      haemodynamic conditions. This process leads to structural alterations within
      vessel walls in different cardiovascular diseases, such as hypertension,
      atherosclerosis, and coarctation of the aorta. OBJECTIVE: We investigated the
      histochemical and immunocytochemical characteristics of morphological lesions in
      coronary atherosclerosis and coarctation of the aorta. METHOD: Twenty-one samples
      of atherosclerotically modified right coronary arteries, divided into 6 segments,
      were analysed. We also examined 10 samples of coarctation segments, excised
      during surgery. The segments were stained histochemically (using orcein and
      alcian blue-PAS), immunocytochemically (using alpha-smooth muscle actin-alpha
      SMA, vimentin, desmin, myosin heavy chains-MHC, CD3, CD45, S-100, and
      Proliferating Cell Nuclear Antigen-PCNA), and for electron microscopy. RESULTS:
      The results of our study of morphological lesions in coronary atherosclerosis
      demonstrated initial functional and then, in the later stages of atherosclerosis,
      morphological, damage to the endothelium. The preatheroma stage revealed the
      presence of intimal dedifferentiation of smooth muscle cells, with the expression
      of vimentin and alpha-SMA, and the lack of expression of desmin. Along with these
      changes, a huge number of foam cells of variant origin were noticed. Some of them
      were CD68-immunoreactive while others were both vimentin- and S-100
      immunoreactive. All examined samples of the coarctation of the aorta demonstrated
      the presence of dedifferentiated smooth muscle cells as well as a diminution in
      cell numbers, followed by apoptotic smooth muscle cells, and the absence of
      inflammatory cells. CONCLUSION: Some foam cells develop from monocyte-macrophage
      lineage (CD68-immunoreactive), while others originate from smooth muscle cells
      (vimentin and S-100-immunoreactive). Coarctation of the aorta is characterised by
      a diminution in cell numbers (apoptosis) as well as their dedifferentiation from
      contractile to synthetic phenotype.

PMID- 16796161
TI  - [Surgical treatment of thoracoabdominal aortic aneurysms].
AB  - INTRODUCTION: Aneurysms simultaneously involving the thoracic and abdominal
      aortas or those aneurysms that include the visceral aortic segment are defined as
      thoracoabdominal aortic aneurysms (ThAAA). Their treatment is one of the most
      difficult surgical problems today. OBJECTIVE: The purpose of this paper is to
      present the early results of the surgical treatment of type IV ThAAA, according
      to the Crawford classification, as well as to analyse the main problems
      encountered during this procedure. METHOD: Between January 2001 and the end of
      2004, 79 patients with type IV ThAAA, according to the Crawford classification
      were treated at the Clinic for Vascular Surgery of the Institute for
      Cardiovascular Diseases of the Serbian Clinical Centre. Lumbotomy combined with
      extrapleural resection of the XI or X rib was used as the operative approach in
      70 cases, while thoracophrenolumbotomy was performed in 9 cases. The aneurysm was
      repaired using the bifurcated Dacron graft in 38 cases and with the tube Dacron
      graft in 41 cases. In 47 cases, visceral arteries were reattached using the
      Carrel patch technique, while in 31 cases, separate revascularisation of the left
      kidney was required. RESULTS: 60 (76%) of our patients survived the first 30
      postoperative days, while 19 (24%) died during this period. The causes of
      mortality included: haemorrhaging, in 4 patients; pulmonary embolism, in 1
      patient; myocardial infarction, in 4 patients; ARDS, in 2 patients; and finally,
      multi-organ system failure, in 8 patients. Statistical analysis showed that
      advanced age (over 70 years), the need for more extensive reconstructive surgery
      along with the implantation of the bifurcated graft, as well as the presence of
      ruptured aneurysms, significantly increased the mortality of the patients.
      CONCLUSION: The surgical management of ThAAA requires a multidisciplinary
      approach. We introduced this procedure in our hospital 4 years ago. The further
      development of this surgery will be of great medical, social, and economic
      importance to our country.

PMID- 16796162
TI  - [Dilemmas and contradictions in the treatment of prostatic cancer].
AB  - INTRODUCTION: There are dilemmas and contradictions in the therapeutic approach
      to each stage of prostatic cancer, and particularly in the application of
      hormonal therapy during the disseminated stages of the disease, where the crucial
      dilemma is: whether to apply constant or temporary (intermittent) hormonal
      therapy. OBJECTIVE: The objective was to compare different hormonal procedures,
      to reach a conclusion about which mode of hormonal therapy or hormonal control of
      disseminated prostatic cancer is best, as well as about which tumour
      characteristics have an effect on the outcome of the treatment. METHOD: Two
      groups of patients with disseminated prostatic cancer were treated using two
      different methods. One group, of 102 patients, was treated using constant
      hormonal therapy, while the other group, of 80 patients, was treated with
      intermittent antiandrogen therapy with a total androgenic blockade (TAB).
      Statistical analysis was used to examine the relative therapeutic effectiveness
      in these two groups. RESULTS: The effectiveness of hormonal therapy depends upon
      the malignancy potential of the tumour, i.e., therapy is the least-effective in
      tumours with the highest malignancy potential, where primary hormonal resistance
      was recorded in 35.7% of the patients, and secondary resistance in 100% of the
      patients, during the follow-up period of 39.1 months. In the group that was
      administered intermittent antiandrogen therapy during nearly the same time
      period, secondary resistance was reported in 20% of the patients, while in the
      group covered by constant therapy, it was reported in 50% of the patients, which
      represented a significant difference (p<0.05). CONCLUSION: The hormonal
      resistance of prostatic cancer relates directly to the malignant potential of the
      tumour, i.e., its grade and stage of malignancy. Intermittent antiandrogen
      application with TAB has a significant effect on the time it takes for a tumour
      to develop hormonal resistance. Therefore, such a procedure reduces the side
      effects and treatment costs of hormonal therapy.

PMID- 16796163
TI  - [Adolescent health].
AB  - INTRODUCTION: Growth, development, and adaptation to numerous internal changes,
      as well as the changing roles of adolescents within the family and the community
      often take place within an environment of drug abuse, increased sexual freedom,
      weakened family structure, and under the strong influence of the media.
      Confronted with these pressures, adolescents often develop risky behaviours,
      which are also important health risks. Up to 75% of deaths and serious morbidity
      in adolescence is associated with risky behaviours. OBJECTIVE: The aim of this
      study is to establish the frequency and types of risky behaviours in adolescents,
      as well as the characteristics of adolescents and families that engage in risky
      behaviours. METHOD: We performed this research with the help of 789 adolescents,
      aged 10 to 19, from elementary and secondary schools in Novi Sad. The
      questionnaire included items on risky behaviours in adolescents, based on: age,
      sex, school achievement, and family characteristics: family composition,
      socioeconomic status, emotional support, family conflicts, and risky behaviours
      of other family members. RESULTS: The results demonstrated that a high percentage
      of adolescents in Novi Sad engage in risky behaviours. Significantly more girls
      than boys engage in numerous risky behaviours. In comparison to their peers,
      adolescents from poor families, from families with either one or both parents
      unemployed, from families with inadequate emotional support, from families with
      frequent conflicts, or from families whose members themselves engage in different
      risky behaviours, engage in numerous risky behaviours significantly more often.
      CONCLUSION: Considering the fact that adolescent engagement in risky behaviours
      significantly affects adolescent morbidity and mortality, it is essential to
      implement comprehensive preventative programmes, which should include all
      adolescents before they start to engage in risky behaviours. In this process, the
      most important role belongs to the family. However, the entire community,
      schools, and health workers, should also play an active part.

PMID- 16796164
TI  - [Aetiological aspects of West Syndrome].
AB  - INTRODUCTION: West Syndrome involves epileptic encephalopathy in infants,
      occurring with an incidence of 5/10000 live births. Its main clinical feature are
      spasms that occur in clusters, which are associated with an EEG pattern called
      hypsarrhythmia and psychomotor retardation in most patients. West Syndrome is
      associated with many underlying conditions and the terms idiopathic, cryptogenic,
      and symptomatic are used for its aetiological subgroups. OBJECTIVE: The objective
      of this investigation was to determine the aetiological diagnosis of patients
      with West Syndrome and to compare the results with other studies. METHOD: In this
      34-year longitudinal prospective one-centre study, 404 patients were studied. All
      patients exhibiting the diagnostic criteria for West Syndrome were investigated
      by clinical and neurological examination, EEG, ophthalmologic, psychological,
      metabolic, genetic, as well as neuroradiological methods, according to their
      particular indications. RESULTS: 36 (8.9%) patients had normal development, in
      whom infantile spasms occurred without any identifiable underlying cause, forming
      the idiopathic group. 51 patients (12.6%) with neurological impairment of unknown
      aetiology formed the cryptogenic group. The greatest number of patients (317 or
      78.5%) formed the symptomatic group, in which neurological features and
      developmental delay preceded the onset of spasms. Disgenetic disorders and
      hereditary metabolic diseases were aetiological factors 44 (10.8%) patients.
      Prenatal and perinatal aetiological factors were revealed in one third of the
      patients (134 or 31%). Postnatal aetiological factors were revealed in 42 (10.2%)
      patients. In our study, disgenetic disorders were registered less frequently and
      perinatal complications more frequently than in other studies. CONCLUSION: Our
      results indicate the possibility of preventing West Syndrome with good quality
      obstetric and neonatal care, as well as the early prenatal diagnosis of brain
      malformations. Modern, sophisticated investigation makes the more accurate
      aetiological diagnosis of West Syndrome possible.

PMID- 16796165
TI  - [Fraud in biomedical literature].
AB  - The basic ethical principles in science are internationally recognised in all
      disciplines of science. The first among these is honesty--both towards oneself
      and towards others. The betrayal of this principle can be seen as deviant
      behaviour, which may result in the most serious violation of the high ethical
      standards of science--scientific fraud. Fraudulent behaviour in biomedical
      sciences is particularly damaging, since all diagnostic and treatment decisions
      are based on what is published in medical literature. The betrayers of science
      undermine, to a great extent, the public trust in science, and may destroy the
      confidence scientists have in each other as well, which is a grave danger to
      science itself. In this article, several high profile cases of scientific fraud-
      involving falsification, fabrication of data, and plagiarism--are described. The
      damaging effect they had on both science and the scientific community led to the
      codification of the concept of Good Scientific Practice (GSP)--an international
      quality standard for designing, conducting, recording, and reporting research.
      The concept of GSP sets internationally valid benchmarks for quality assurance,
      and also provides safeguards against scientific dishonesty and fraud.

PMID- 16796166
TI  - [Oxygenation level as a factor in stem cell maintenance].
AB  - This article will describe the decade-long genesis of a research project and
      review its main results. These results point to oxygenation level being a
      physiological regulator of haematopoietic stem cell maintenance because: (1) very
      low oxygen concentrations (approximately 0.1%) enable the preservation of the
      quiescent (G0) stem cell pool; (2) low oxygen concentrations (approximately 1%)
      are compatible with the proliferation of primitive stem cells but inhibit their
      differentiation, i.e. enable their self-renewal; (3) moderately low oxygen
      concentrations (approximately 3%) allow a balance between differentiation and
      self-renewal, permitting the simultaneous amplification of progenitors and the
      maintenance of stem cell activity; and (4) very high oxygen concentrations, like
      those in the air (20-21%), enhance the differentiation of primitive stem cells,
      abrogating their self-renewal capacity. In spite of the fact that these oxygen
      concentrations do not exist in tissues in vivo, they are usually used for in
      vitro cell growth. These results represent a new insight into the regulatory
      mechanisms of haematopoiesis. In that light they are cited in top biomedical
      literature and accepted as being relevant to the development of tissue and cell
      engineering. In that respect, we are working on the adaptation of culture
      oxygenation to improve existent ex vivo expansion techniques. We are also trying
      to improve the techniques of ex vivo production of red blood cells in the same
      manner. Our other ongoing research projects are directed at improving the
      conservation of stem cells at low temperatures (but above freezing point) within
      a liquid medium, by decreasing oxygen and increasing CO2 concentrations.

PMID- 16796167
TI  - [Role of gene polymorphism in development of thromboses].
AB  - The development of thromboses is one of the most common causes of morbidity and
      mortality in the Western world. The perturbation of haemostasis is the central
      event in the pathogenesis of all thromboses. Most patients with thromboses have
      no recognisable associated haemostatic disorders. However, some patients do
      manifest hereditary hypercoagulable states, which contribute to the development
      of thromboses as well as other clinical manifestations, such as miscarriages and
      foetal complications. The major determinants of thrombosis include both
      environmental influences and genetic factors. Transient or long-lasting
      environmental influences may play important roles in arterial and venous
      thromboses. Haemostatic perturbance may also be genetically determined and exert
      a life-long influence. Specific mutations of genes predisposed to thrombosis,
      such as deficiency of antithrombin, protein C, or protein S, are found in
      relatively small number of families. In the absence of genetic deficiencies,
      thrombosis occurs in the older population, largely within the context of marked
      environmental influences (such as surgery, obesity, and malignancy). In contrast,
      familial thrombosis, associated with gene mutation, is associated with a younger
      age. The general importance of gene polymorphism was established after the
      recognition of activated protein C resistance (APCR) due to gene polymorphism
      G1691A in factor V (Factor V Leiden). This single gene defect increases the risk
      of venous thrombosis, without interaction with other genetic or environmental
      risk factors. The development of APCR led to many other investigations of gene
      polymorphism, such as prothrombin 20210, thrombomodulin, factors in the
      coagulation and fibrinolytic system, glycoproteins of platelet membranes, as well
      as polymorphism C677T of methylene tetrahydrofolate reductase. The number of
      potential genetic risk factors for occlusive thrombotic disease has increased
      significantly. Most of these gene polymorphisms increase the risk of venous
      thrombosis but there is no strong evidence of their influence as far as arterial
      thrombosis is concerned.

PMID- 16796168
TI  - [Individualisation of therapy in acute nonlymphoblastic leukaemia].
AB  - Acute nonlymphoblastic leukaemia involves the dynamic and individual coupling of
      four groups of significant prognostic factors: biological potential of the
      patient, leukaemic clone, normal haematopoiesis, and therapy. The active,
      dynamic, and timely prognosis of an unfavourable outcome represents a solid basis
      for the individual adaptation of antileukaemic and supportive therapy. A part of
      the ANLL NS 03 programme for the individualised therapy of acute nonlymphoblastic
      leukaemia in patients no older than 60 years will be described. The programme is
      based on a network of prognostic models, identifying predictors and preventive
      measures against an unfavourable outcome. The crucial point of the ANLL NS 03
      programme is to determine the optimal timing for the transplantation of
      allogeneic and autologous haematopoietic stem cells. Indicators of early death
      include the age of the patient, infection, and hemorrhagic syndrome. According to
      our models, the predictors of fatal bleeding and fatal infection are
      hyperleukocytosis, leucopenia, and granulocytopenia, respectively. Resistance to
      cytostatics can be predicted on day 14 from the onset of therapy using two
      original cytological-mathematical parameters: the absolute blast count (ABC)
      forming the intensity dimension, and parameter S forming the selectivity
      dimension, of the early effects of the first induction treatment. The ABC and S
      values determine the structure and timing of the second induction treatment.
      Transplantation of autologous and allogeneic haematopoietic stem cells within the
      ANLL NS 03 programme is applied selectively during the early stages of the first
      remission in patients at high risk of an early relapse. Predictors of early
      relapse are leukocyte counts higher than 30x10(9)/l, remission induction during
      the second treatment, and the presence of myelodysplasia. In all other patient
      categories and in patients with cytogenetically favourable forms of acute
      nonlymphoblastic leukaemia, transplantation is postponed until the second
      remission of the disease.

PMID- 16796169
TI  - [Clinical pathology].
AB  - This work describes the basic elements of pathology used in clinical practice.
      Pathology plays an important role in clinical and scientific work, but only a few
      areas of pathology will be covered. Although the contribution of oncological and
      surgical pathology to therapy is the most well known, the cases chosen here will
      involve infectious pathology, diseases of the kidney and the liver, autoimmune
      diseases, as well as organ transplantation. Especially important is the
      description of methods that enable more accurate morphological diagnoses, such as
      histochemistry, immunohistochemistry, immunofluorescence, and electronic
      microscopy. Previous experience and joint work with clinical doctors have enabled
      the definition of significant morphological elements as well as of essential
      methods of pathohistological diagnosis. Besides, as is often the case, although
      disease symptoms are difficult to discern and biochemical results do not show
      significant changes compared to normal values, the results of biopsy come as a
      surprise to clinical doctors. For example, in virus hepatitis B involving so
      called asymptomatic HBsAg carriers, we discovered every morphological form of
      hepatitis, from minimal lesions to chronic, persistent, and active hepatitis.
      With hepatitis C, certain morphological lesions point to the etiopathogenesis of
      this disease and thus help to confirm the diagnosis and to instigate therapy on
      time. Another significant experience involves kidney biopsies in cases when
      clinical findings are asymptomatic. Often, in such cases, morphological findings
      point to glomerulonephritis and glomerulopathy at different stages. Timely and
      subtle morphological diagnostics offer a more precise explanation for the
      pathological injury of tissues than other diagnostic methods. In this way, by
      adopting new methods, the work of pathologists is included more and more in
      everyday clinical practice. The inclusion of pathologists in a transplantation
      team makes sure a proper selection of the organ for transplantation is carried
      out and ensures a reliable evaluation of the condition of the transplanted organ,
      enabling appropriate therapy. Autoimmune, hereditary diseases are almost
      impossible to recognise unless a biopsy is performed as in the examples given. In
      this work, the 30-year-long results of the cooperation between clinical doctors
      and pathologists are presented and compared with similar results from modern
      literature, together with numerous examples that represent significant
      experiences and achievements of our medicine.

PMID- 16796170
TI  - [Improved exercise tolerance can be achieved in chronic obstructive pulmonary
      disease (COPD) by means of non-pharmacological treatment].
AB  - A 67-year-old man with severe COPD and a 56-year-old woman with very severe COPD
      were dyspnoeic during even mild exercise, so that they could no longer take care
      of themselves properly. The man followed a rehabilitation programme aimed at
      restoration of his physical condition and self-confidence and optimisation of his
      nutritional status. The woman was subjected to surgery to reduce her lung volume.
      Both were subsequently able to live independently. During the past decade,
      considerable attention has been given to the non-pharmacological treatment of
      patients with COPD. Together with optimal pharmacotherapy, COPD can be
      effectively treated by rehabilitation, lung volume reduction surgery and lung
      transplantation. Clinically relevant improvements can be achieved in both
      exercise capacity and quality of life. The clinical condition, lung function and
      radiological findings guide the choice of treatment in each individual.

PMID- 16796171
TI  - [COPD: new insights].
AB  - Both morbidity and mortality due to chronic obstructive pulmonary disease (COPD)
      are increasing. In the Netherlands there are between 500,000 and 1 million
      patients. It has now been recognized that airway obstruction can be partially
      reversed and that inflammation and oxidative stress play a part in the
      pathophysiology. New disease outcome measures in scientific research and in the
      clinical setting include symptoms, quality of life, exacerbation frequency and
      changes in exercise tolerance. Bronchus-dilating medication is now the standard
      pharmacotherapy and at every stage of COPD bronchodilators administered by
      inhaler are advised. The introduction of long-acting beta2-agonists is an
      advancement in treatment. The long-term effects of tiotropium are awaited.
      Acetylcysteine seems to be indicated in frequent exacerbations or hyperinflation.
      Where non-medicinal treatment is concerned, nutrition, exercise and particularly
      stopping smoking are important. Company medical officers can give advice
      concerning work and the work situation. Home care, hospital admissions and
      medication are the main costs, particularly in more serious COPD.

PMID- 16796172
TI  - [Acetylcysteine in the treatment of severe COPD].
AB  - Oxidative stress plays a role in the pathogenesis and progression of chronic
      obstructive pulmonary disease (COPD). Oxidants cause structural changes in
      essential components of the lung, leading to irreversible damage of both the
      parenchyma and the airway walls. Acetylcysteine is a precursor of glutathione, an
      important antioxidant in the lung with a protective effect against internal and
      external toxic agents. In placebo-controlled studies, maintenance therapy with
      acetylcysteine in patients with chronic bronchitis (usually also COPD) reduced
      the viscosity of the sputum, the severity of coughing, the number of bacteria in
      the airways, the number and severity of influenza-like episodes, the number of
      exacerbations and the number of readmissions. In studies among COPD-patients,
      acetylcysteine had no effect on the downward trend of the FEV1 but did improve
      the functional residual capacity; itaffected the number of exacerbations only in
      those patients who were not on inhaled corticosteroids. The agent may well
      deserve a place in the treatment of patients with severe COPD who have frequent
      exacerbations and are not using inhaled corticosteroids.

PMID- 16796173
TI  - [Tiotropium, a long-acting bronchodilating agent for the treatment of COPD].
AB  - The goals of COPD management according to the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) guideline are: prevention of disease progression,
      relief of symptoms, improvement of exercise tolerance and the quality of life,
      prevention and treatment of exacerbations and complications, and reduction of
      mortality and adverse effects. These correspond to the goals formulated in the
      Dutch 'National transmural agreements on COPD'. Bronchodilators play a key role
      in the pharmacological treatment and with the availability of tiotropium, a long
      acting anticholinergic bronchodilator, it has become important to decide at what
      moment this is indicated in COPD management. In comparative studies, tiotropium
      was an effective long-acting bronchodilator that had a favourable effect not only
      on lung function but also on the other parameters indicated in the GOLD
      guideline. When maintenance treatment with bronchodilators is needed, one should
      consider a long-acting bronchodilator. In view of the additive positive effects,
      tiotropium is the bronchodilator of choice. In case of severe symptoms, a
      combination of tiotropium with a long-acting beta2-sympathicomimetic agent is
      recommended.

PMID- 16796174
TI  - [Guideline for the non-pharmacological treatment of COPD].
AB  - The non-pharmacological treatment of patients with chronic obstructive pulmonary
      disease (COPD) comprises a large number of related components. Active case
      finding is advocated in (ex-)smokers above the age of 40 who either cough or have
      2 respiratory-tract infections per year. Structured self-management programmes
      may have positive effects; follow-up is of importance to prevent relapse of
      unhealthy behaviour. Patients with COPD must not smoke. Exercise training is
      essential in all stages of COPD; an exercise test should be done first,
      especially in severe COPD. Exercise training should preferably be incorporated in
      a pulmonary-rehabilitation programme if other components of such a programme are
      also indicated. Certain breathing exercises may be considered in patients that
      feel anxious or tense. Nutritional support combined with exercise training should
      be considered in patients with severe COPD and underweight, involuntary weight
      loss or a deficiency of fat-free mass. There are limited indications that
      psychosocial interventions may have a positive effect on the well-being and
      psychosocial function of patients with COPD. An exercise test to assess the
      maximum tolerated energy expenditure is indicated in COPD patients that
      experience limitations on their physical capabilities during work. Maintenance
      therapy with supplemental oxygen should be considered in case of hypoxia (PaO2 <
      7.3 kPa) and if the PaO2 = 7.3-8.0 kPa combined with indications of pulmonary
      hypertension, peripheral oedema or a haematocrit > 0.55. A yearly influenza
      vaccination is indicated.

PMID- 16796175
TI  - [The Netherlands Expertise Center for Occupational and Respiratory Disorders].
AB  - In 2000 the Netherlands Expertise Centre for Occupational Respiratory Disorders
      (NECORD) was started as a centre of expertise in occupational health. The centre
      received a grant from the ministry of Health Welfare and Sport for a period of 5
      years. Their mission was to collect, develop and implement knowledge in the
      fields of diagnosis, treatment, reintegration and prevention of work-related
      health- and occupational disorders. In cooperation with two other institutes for
      health, NECORD has become a multidisciplinary clinical occupational respiratory
      health service. Occupational hygienists, occupational health physicians and chest
      physicians are working on three programmes: research projects on the prevalence
      and monitoring of respiratory health effects resulting from exposure to
      substances in the work place; patient care (out-patient clinic); and support of
      professionals (website, helpdesk, development and implementation of guidelines,
      education and postgraduate training).

PMID- 16796176
TI  - [Projections of future resource use and the costs of asthma and COPD in the
      Netherlands].
AB  - OBJECTIVE: To determine the health-care utilisation and associated costs for
      asthma and chronic obstructive pulmonary disease (COPD) in the Netherlands for
      the year 2000 and to estimate future costs by means of projections. DESIGN:
      Descriptive and explorative. METHOD: The costs were based on data regarding
      resource use in 2000 obtained from representative national registries and
      surveys. The costs were specified by gender and age category and for COPD also by
      severity. Three projections for the costs of asthma and COPD were made by means
      of prevalence projections: first assuming constant resource use and constant
      prices, second assuming asthma- and COPD-specific trends in the costs for
      hospital care (asthma, -4.7% and COPD, -4.1% per year) and medication (+4.9% per
      year), and third by adding general trends for the remaining types of care.
      RESULTS: Total costs for the year 2000 for asthma (452,000 patients) and COPD
      (306,000 patients) were estimated to be 141 and 280 million Euros, amounting to
      313 en 915 Euros per patient or 9 and 18 Euros per inhabitant, respectively.
      Projections of total prevalence for the year 2025 varied between 478,000 and
      568,000 patients for asthma and between 479,000 and 494,000 patients for COPD.
      Assuming constant resource use and prices, the costs in 2025 were projected to
      increase to amounts between 167 and 181 million Euros for asthma and 443 and 495
      million Euros for COPD. Projections including the estimated trends in costs for
      hospital care, medication and the costs for other types of care predicted a
      sharper increase. CONCLUSION: Costs for asthma and COPD together (421 million
      Euros) amounted to 1.3% of the total Dutch health-care budget in 2000. Almost 70%
      of these costs were for COPD. Projections for 2025 showed that the costs for COPD
      will increase more than the costs for asthma.

PMID- 16796177
TI  - [Diffuse panbronchiolitis in an Asian woman with severely obstructed pulmonary
      disease].
AB  - A 41-year-old woman was referred for severely obstructed pulmonary disease 4
      years after she stopped smoking. Treatment for chronic obstructive pulmonary
      disease (COPD) had no effect and lung function worsened in the following years.
      The clinical, radiological and pathological characteristics led us to the
      diagnosis of diffuse panbronchiolitis. She was treated with clarithromycin. After
      1 year, major improvement was seen in clinical, radiological and spirometric
      features. Diffuse panbronchiolitis is a rare obstructive disorder that is usually
      seen in people of Japanese descent. Patients respond well to treatment with low
      dose macrolide treatment.

PMID- 16796178
TI  - [Cystic adventitial degeneration of the popliteal artery; an unexpected cause of
      intermittent claudication].

PMID- 16796179
TI  - [Questionable efficacy and safety of activated drotrecogin alpha (activated
      protein C) in the treatment of severe sepsis].

PMID- 16796180
TI  - [Super-GAU suicide--the family physician as crisis manager].

PMID- 16796181
TI  - [Pathways out of a suicidal crisis].

PMID- 16796182
TI  - [Is a jolt passing through oncology?].

PMID- 16796183
TI  - [Gallbladder with suspected carcinoma. Finally the surgeon made the correct
      diagnosis].

PMID- 16796184
TI  - [By the year 2030 some 40% of the German population could be Type 2 diabetics-
      the big bang in the public health system].

PMID- 16796185
TI  - [Microalbuminuria in diabetes: setting the points for treatment].
AB  - Both type 1 and type 2 diabetes mellitus have a cumulative risk of 25-40% for the
      development of microalbuminuria 25 years into the disease. In type 2 diabetes
      micro- and macroangiopathic complications, and frequently hypertension, may also
      develop. This means that the risk of a type 2 diabetic with microalbuminuria of
      developing cardiovascular disease is three times greater than that of a diabetic
      with no renal involvement. Annual screening for microalbuminuria should therefore
      be obligatory. An increasing albumin excretion rate (AER) is considered an
      indication for an elevated cardiovascular risk. Studies have shown that the rate
      of cardiovascular events in diabetics with microalbuminuria and hypertension can
      be reduced only by the combined treatment of hypertension, hyperglycemia,
      hyperlipidemia and microalbuminuria.

PMID- 16796186
TI  - [Diagnostic and therapeutic options in diabetic retinopathy].
AB  - Diabetes mellitus is the systemic disease that most often leads to blindness.
      Since the diminishment of visual acuity is a late symptom of the disease,
      screening examinations are of particular importance, as only in this way can the
      optimal time point for treatment be determined. Stage-oriented laser therapy
      prevents blindness due to macular edema or proliferative diabetic retinopathy.
      For a number of years, vitreoretinal surgery has enabled the treatment of late
      ocular manifestations such as bleeding into the vitreous body and traction
      retinal detachment. With appropriate stage-oriented treatment, hopeless cases of
      diabetic retinopathy ending in blindness should become the exception. The only
      useful and confirmed effective medical treatment capable of delaying this late
      complication continues to be careful blood glucose and blood pressure control.

PMID- 16796187
TI  - [The diabetic foot].
AB  - As a means of achieving a reduction in the amputation rate in patients with a
      diabetic foot syndrome, the early diagnosis and specialized treatment of
      peripheral circulatory disorders is of eminent importance. Treatment includes
      pressure relief, wound cleanup and stage-oriented local wound management,
      measures to improve circulation, and the appropriate treatment of bacterial
      infection. Useful preventive measures include the training of diabetics, regular
      foot care, and the provision of appropriate footwear.

PMID- 16796188
TI  - [Strategies for talking to the patient with sexual dysfunction in the doctor's
      office].
AB  - The use of a questionnaire for initiating talks about the topic of sexual
      disorders and the efficacy and acceptance by the physician and patient of various
      communication strategies, were investigated. Each of a total of 1191 general
      practitioners distributed a health questionnaire which contained questions on
      sexuality to 150 men aged 30 and above. In a total of 10,622 first talks on
      sexual health, the questionnaire met with a high level of acceptance, and was the
      trigger for talks in 54% of the cases. More than two-thirds of the patients
      reacted positively to such talks, speaking freely and readily, and relieved that
      this aspect of their lives was being addressed. In 75% of the patients an
      erectile dysfunction was diagnosed, in 27% further diagnostic measures were
      prescribed, and in 60% treatment was initiated. In the exes of the physician, the
      clearly signaled readiness to talk and the discussion of treatment options were
      the most favorable communication strategies.

PMID- 16796189
TI  - [Allergic rhinitis. This year the pollen count is expected to be high].

PMID- 16796190
TI  - [Are family physicians less competent than gynecologists? Many colleagues ignore
      chances in the EMB system].

PMID- 16796191
TI  - [Calculating no. 03210. This way you may see the patient only once].

PMID- 16796192
TI  - [Alpha-1-antitrypsin deficiency. Consider it already in children and
      adolescents!].

PMID- 16796193
TI  - [Genetic risk factor AAT deficiency. Also heterozygotes carry the risk of
      pulmonary emphysema].

PMID- 16796194
TI  - [Cardiac risk in post-infarct patients. What allows the diabetic heart to beat
      longer? (interview by Dr. Judith Neumaier)].

PMID- 16796195
TI  - [Hypertensive patient with enlarged heart. Caution, risk of atrial
      fibrillation!].

PMID- 16796196
TI  - [Backache is often caused by strained muscles].

PMID- 16796197
TI  - [What is growing here? Pigmented villonodular synovitis].

PMID- 16796198
TI  - The health charter.

PMID- 16796199
TI  - Recent debate regarding PROFMED in the SADA journal.

PMID- 16796200
TI  - An investigation into digital colour recipe prediction for use in dentistry.

PMID- 16796201
TI  - Dental specialist training in South Africa--demographic characteristics 1985
      2004.
AB  - This short communication complements a recently published dental undergraduate
      analysis, and analyses the demographic profile of dental specialists trained from
      1985-2004, as well as that of the registrars in training (in 2005). A total of
      309 dental specialists were trained from 1985-2004, of these 86% were males and
      74% White. Of the registrars, two-thirds are males and a quarter Black. The
      dental faculties and the Health Professions Council of South Africa (HPCSA) face
      a significant challenge to find innovative ways to address these disparities, as
      well as the urban/rural and private/public sector maldistribution of dental
      specialists, and to develop a more rational basis for training dental specialists
      for the country. Dealing with these disparities should improve access to dental
      specialist care for the poor and rural populations.

PMID- 16796202
TI  - Updates on local anaesthetics.

PMID- 16796203
TI  - Management strategies of the unsalvageable tooth.
AB  - A tooth is deemed unsalvageable when it can no longer be preserved for use of
      function or aesthetic purposes. If proper treatment planning is done, tooth
      extraction can be performed with adjunctive procedures, to provide a more
      predictable restorative outcome for the patient. This review paper summarizes the
      possible treatment strategies available for the management of a tooth with a poor
      prognosis, so as to manage the patient better before the restorative treatment
      phase commences. CLINICAL RELEVANCE: The management of an unsalvageable tooth
      using interdisciplinary approaches offers the clinician strategies for providing
      a more favourable restorative outcome.

PMID- 16796204
TI  - General practitioner's pathology case 3.

PMID- 16796205
TI  - General practitioner's radiology case 40.

PMID- 16796206
TI  - How to help smokers quit: part 1.

PMID- 16796207
TI  - News alert for mothers: having children at home doesn't increase your risk for
      severe daytime sleepiness or fatigue.

PMID- 16796208
TI  - What should we be measuring? Defining the "P" in PLMS.

PMID- 16796209
TI  - Stress measures linking sleep apnea, hypertension and diabetes--AHI vs arousals
      vs hypoxemia.

PMID- 16796210
TI  - Looking beyond the polysomnograph in ADHD.

PMID- 16796211
TI  - Staying awake for dinner--staying asleep until breakfast.

PMID- 16796212
TI  - Master of rhythms: Mircea Steriade.

PMID- 16796213
TI  - What are the important risk factors for daytime sleepiness and fatigue in women?
AB  - STUDY OBJECTIVE: To analyze the relation between different risk factors and
      excessive daytime sleepiness (EDS) and fatigue in women from a general-population
      sample. DESIGN: Cross-sectional population study. SETTING: The municipality of
      Uppsala, Sweden. PARTICIPANTS: Five thousand five hundred eight women (response
      rate 73.3%) aged 20 to 60 years. MEASUREMENTS AND RESULTS: EDS, fatigue, and
      potential risk factors were assessed in a self-administered questionnaire. Risk
      factors for EDS and fatigue were analyzed using a multiple logistic regression
      model. In the whole population, 16.1% of the women reported EDS and 14.3%
      fatigue. The risk of having EDS and fatigue decreased with increasing age:
      adjusted odds ratios (95% confidence interval) for EDS and fatigue were 0.73
      (0.66-0.88) and 0.86 (0.77-0.96) per 10 years, respectively. The combination of
      anxiety and depression was highly related to both EDS and fatigue (4.51 [3.51
      5.79] and 7.00 [5.39-9.10], respectively). Insomnia, somatic disease, snoring,
      being overweight, and being on sick leave were also independently related to both
      conditions, whereas lifestyle factors, such as physical inactivity and smoking,
      were related to fatigue but not to EDS. Having children did not influence the
      risk of either EDS or fatigue. CONCLUSION: Psychological distress, insomnia, and
      somatic disease are the most important conditions in women reporting daytime
      sleepiness and fatigue. Because 1 in 5 (21%) of the women in this study reported
      sleepiness, fatigue, or both, interventions that improve psychiatric health and
      reduce insomnia are important in improving the quality of life in women with
      these sleep symptoms.

PMID- 16796214
TI  - New approaches to the study of periodic leg movements during sleep in restless
      legs syndrome.
AB  - STUDY OBJECTIVES: To describe a new approach for the analysis of quantity, type,
      and periodicity of the leg motor activity during sleep in patients with restless
      legs syndrome (RLS) and periodic leg movements (PLM). METHODS: The following
      parameters were taken into account for LM: duration, amplitude, area under the
      curve, sleep stage, side, interval, and bilaterality. The analysis of inter-LM
      intervals was carried out by drawing their distribution graphs. A new index
      evaluated their periodicity and was validated by means of a Markovian analysis.
      The differences in inter-LM intervals, LM duration, and area under the curve
      between normal controls and patients and between the 3 patient subgroups
      identified on the basis of their periodicity were statistically analyzed.
      SETTING: N/A. PARTICIPANTS: Sixty-five patients with RLS and periodic LM and 22
      young healthy controls. MEASUREMENTS AND RESULTS: The RLS patients' inter-LM
      interval distribution graph showed a wide peak with a maximum located at around
      15 to 30 seconds and extending from 10 to 90 seconds, not present in controls,
      and another peak for intervals less than 8 seconds, higher than that of controls.
      Three patient subgroups were identified with different proportions of these 2
      peaks, periodicity, and Markovian parameters. Periodicity was not dependent on
      the periodic leg movement index. Patients showing the peak mainly at around 15 to
      30 seconds tended to show slightly longer and higher area under the curve LM than
      did the other 2 subgroups. CONCLUSIONS: Our new approach seems to be useful in a
      new qualitative differentiation among patients with PLM, which is not possible by
      using the simple PLM index.

PMID- 16796215
TI  - Absence of postexercise and delayed facilitation of motor cortex excitability in
      restless legs syndrome: evidence of altered cortical plasticity?
AB  - STUDY OBJECTIVE: Restless legs syndrome (RLS) is a neurologic disorder with well
      defined clinical and diagnostic criteria but the pathophysiology of which is
      unclear. Previous studies have suggested alterations in motor cortex function in
      RLS. We aimed to compare motor cortex plasticity in subjects with RLS versus
      healthy controls. DESIGN: Biphasic single-pulse transcranial magnetic stimulation
      (TMS) of the nondominant hemisphere was used to define motor evoked potential
      (MEP) amplitude, motor threshold, and silent period. Subjects also performed 3
      blocks (30-s, 60-s, and 90-s duration) of a bimanual motor task (exercise
      condition). Amplitude of MEPs elicited immediately after each block, and then
      after a 15-minute rest period were compared with baseline. The time course of
      intracortical inhibition was also tested using paired-pulse TMS at 1- to 6
      millisecond interstimulus intervals. SETTING: Clinical neurophysiology laboratory
      in a General Hospital. STUDY PARTICIPANTS: For the single-pulse TMS procedures,
      the RLS group included 11 patients affected by primary RLS and the control group
      included 11 age- and sex-matched normal subjects. For the paired-pulse TMS
      procedures, there were 9 patients and 6 controls. INTERVENTIONS: None. RESULTS:
      There were no group differences in motor threshold and MEP amplitudes, but the
      silent period was significantly shorter in subjects with RLS. Compared with
      baseline, control subjects had larger MEP amplitudes after 30 and 60 seconds of
      exercise and also after the rest period. In contrast, MEP amplitudes in patients
      with RLS were not significantly different from baseline after any of the exercise
      conditions or following the rest period. Patients with RLS also had decreased
      short-latency paired-pulse inhibition. CONCLUSIONS: Findings show abnormal motor
      cortex inhibition and cortical excitability differences in RLS. We suggest the
      possibility of alterations in movement-related cortical plasticity in RLS.

PMID- 16796216
TI  - Differences in polysomnography predictors for hypertension and impaired glucose
      tolerance.
AB  - RATIONALE: It is unclear which indexes of physiologic stress obtained from
      polysomnography best predict sleep apnea-related outcomes. We assessed the
      relationships between various indexes of sleep-associated physiologic stress with
      2 outcomes: hypertension and impaired glucose tolerance. METHODS: Three hundred
      ninety-four participants in the Cleveland Family Study underwent overnight
      polysomnography, blood pressure measurements, and an oral glucose tolerance test.
      Graphical techniques and generalized estimating equations for logistic models
      were used to quantify the relationship between polysomnography indexes and to
      estimate the odds of each outcome, adjusting for age, sex, race, and body
      habitus. RESULTS: Of the sample, 31% had hypertension, and 32% had impaired
      glucose tolerance. The odds of hypertension increased approximately 20% per 5
      unit increase in arousal index (odds ratio 1.22; 95% confidence interval 1.06,
      1.41). Weaker associations of hypertension with the apnea-hypopnea index and
      oxygen-saturation variables were seen. In contrast, the strongest index
      associated with impaired glucose tolerance was time spent at an oxygen saturation
      of < 90%; individuals with at least 2% of time spent at a saturation level less
      than 90% had 2.33 times (95% CI 1.38, 3.94) the odds of impaired glucose
      tolerance. CONCLUSIONS: These data are consistent with disparate pathways
      mediating hypertension and impaired glucose tolerance. Vascular responses may be
      more directly related to sympathetic surges and arousals, whereas metabolic
      sequelae may be mediated more by hypoxic stress. One single index from
      polysomnography may not be adequate to fully predict the myriad health outcomes
      associated with sleep apnea.

PMID- 16796217
TI  - Spontaneous arousability in prone and supine position in healthy infants.
AB  - STUDY OBJECTIVE: Compared with control infants, those who will be future victims
      of sudden infant death syndrome (SIDS) show a decreased arousability during
      sleep, with fewer cortical arousals and more-frequent subcortical activations.
      These findings suggest an incomplete arousal process in victims of SIDS. Prone
      sleep position, a major risk factor for SIDS, has been reported to reduce arousal
      responses during sleep. The present study was undertaken to evaluate whether the
      prone sleep position impairs the arousal process in healthy infants. METHODS:
      Twenty-four healthy infants were studied polygraphically during 1 night; 12
      infants regularly slept supine and 12 infants regularly slept prone. Infants were
      matched for sex, gestational age, and age at recording. Arousals were
      differentiated into subcortical activations or cortical arousals, according to
      the presence of autonomic and/or electroencephalographic changes. Frequencies of
      subcortical activations and cortical arousals were compared in the prone- and the
      supine-sleeping infants. RESULTS: Compared with supine sleepers, prone sleepers
      had significantly fewer cortical arousals during rapid eye movement (REM) sleep
      (p = .043). There were no significant differences in cortical arousals between
      the 2 groups during non-REM sleep. No significant differences were seen in the
      frequencies of subcortical activations during both REM and non-REM sleep between
      supine and prone sleepers. The ratio of cortical arousal to subcortical
      activation showed no significant differences between the prone and the supine
      sleepers. CONCLUSIONS: Prone sleep position decreased the frequency of cortical
      arousals but did not change the frequency of subcortical activations, as has been
      previously found in SIDS victims. These results suggest specific pathways for
      impairment of the arousal process in SIDS victims.

PMID- 16796218
TI  - NREM sleep instability is reduced in children with attention
      deficit/hyperactivity disorder.
AB  - STUDY OBJECTIVES: To evaluate non-rapid eye movement sleep instability (NREM), as
      measured by the cyclic alternating pattern (CAP), in a cohort of children with
      attention-deficit/hyperactivity disorder (ADHD) and normal controls. DESIGN:
      Prospective study. SETTINGS: Sleep laboratory. PARTICIPANTS: Twenty consecutive
      outpatients with ADHD (18 boys and 2 girls; age range 6-13 years, mean age 9.3
      years) and 20 normal children matched for age and socioeconomic status underwent
      polysomnographic recordings for 2 consecutive nights in a standard laboratory
      setting. Sleep was visually scored for sleep macrostructure and CAP, according to
      standard criteria. MEASUREMENTS AND RESULTS: Children with ADHD showed
      significantly reduced sleep duration and increased rate of stage shifts. All
      children with ADHD had an apnea-hypopnea index less than 1. Those with ADHD
      presented lower total CAP rates and lower CAP rates during sleep stage 2 than did
      normal controls. Moreover, in children with ADHD, we found a lower number of CAP
      sequences and a reduced total A1 index, mainly in light sleep (sleep stages 1 and
      2). We did not find differences in A subtype percentages, but there was a longer
      duration of A1 subtypes in children with ADHD. CONCLUSIONS: Children with ADHD
      showed a lower CAP rate and a lower number of CAP sequences; this supports the
      hypothesis of the existence of a hypoarousal state in these patients.

PMID- 16796219
TI  - Event-related potentials in patients with insomnia and sleep-related breathing
      disorders: evening-to-morning changes.
AB  - STUDY OBJECTIVES: The relationship between event-related potentials (ERPs) and
      sleep alterations in patients with sleep disorders is still controversial.
      Whether the ERP alterations are affected by sleep loss and sleep discontinuity
      can be addressed by studying presleep-to-postsleep changes in ERPs. We
      investigated if presleep-to-postsleep ERP latencies and amplitudes differ in
      patients with insomnia and sleep-related breathing disorders and whether these
      changes are affected by the degree of subjective and objective sleep alterations.
      METHODS: Fifteen patients with a diagnosis of insomnia, 45 patients with sleep
      related breathing disorders, and 13 healthy controls were examined. Auditory ERPs
      were measured in the evening before sleep and in the morning after
      polysomnography. Subjective sleepiness and sleep quality were assessed by the
      Epworth Sleepiness Scale and the Saint Mary's Hospital Quality of Sleep
      Questionnaire. RESULTS: Analysis of evening-to-morning ERP variations did not
      reveal significant between-group differences in N100 latency and amplitude or in
      P200 and P300 amplitudes. Patients with sleep-related breathing disorders had a
      significant lengthening of P200 and P300 latencies in the morning, compared with
      controls and insomniacs. A trend to delayed morning P300 was present in patients
      with insomnia but did not reach statistical significance. The evening-to-morning
      ERP differences were not significantly related to subjective sleep quality,
      indexes of sleep fragmentation, or total sleep time. CONCLUSIONS: ERPs are
      sufficiently sensitive to assess attention dysfunction in patients with sleep
      disorders when presleep-to-postsleep changes are considered. The lack of
      relationship between indexes of sleep loss and sleep fragmentation and presleep
      to-postsleep ERP changes might suggest that other factors outside sleep
      alterations affect ERP deterioration in patients with sleep disorders.

PMID- 16796220
TI  - Assessment of sleep in women with night eating syndrome.
AB  - STUDY OBJECTIVES: Evaluation of sleep in subjects with night eating syndrome
      (NES). DESIGN: Polysomnographic and questionnaire comparisons between subjects
      with NES and controls. SETTING AND PARTICIPANTS: Fifteen women with NES (mean +/-
      SD = 41 +/- 8 years) and 14 women (comparable age and weight) without NES (39 +/-
      10 years) were studied in the laboratory for 3 days. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: Subjects with NES did not differ from controls in
      timing of sleep onset or offset. They had less stage 2 sleep than controls
      (minutes, p = .012; percentage, p = .016) and less stage 3 sleep (p = .023),
      which contributed to their having a lower total sleep time (p = .05) and reduced
      sleep efficiency (p = .03). Subjects with NES did not have more awakenings than
      controls, but 93.3% of them ate on awakening during all 3 nights, while 92.9% of
      controls did not eat on any night. Logistic discriminant analyses identified a
      multiple sleep parameter model associated with increased likelihood of NES that
      had sensitivity of 84.6% and specificity of 76.9%. Patients with NES were more
      depressed than controls (p < .001) and reported greater sleep disturbance that
      included lower sleep quality (p < or = .001), reduced sleep duration (p < or =
      .001), and increased number of awakenings (p < or = .001). CONCLUSIONS: Patients
      with NES appear to have sleep maintenance insomnia rather than sleep-related
      eating disorder or a parasomnia. The maintenance of normal timing for sleep-wake
      behavior in the presence of a phase delay in the timing of caloric intake
      suggests this disorder reflects a state of internal circadian desynchrony
      associated with significant sleep complaints. It remains unknown whether the
      sleep disturbance precedes the abnormally timed eating.

PMID- 16796221
TI  - Subjective and objective measures of adaptation and readaptation to night work on
      an oil rig in the North Sea.
AB  - STUDY OBJECTIVES: To study the adaptation and readaptation processes to 1 week of
      night work (6:30 PM to 6:30 AM) followed by 1 week of day work (6:30 AM to 6:30
      PM). DESIGN: Part of a randomized, placebo-controlled, crossover field study.
      Here, data from the placebo arm are presented. SETTING: Oil rig in the North Sea.
      Work schedule: 2 weeks on a 12-hour shift, with the first week on the night shift
      and the second week on the day shift. PARTICIPANTS: Subjects complaining about
      problems with adjusting to shift work. Seventeen workers completed the study.
      INTERVENTIONS: N/A. MEASUREMENTS: Subjective and objective measures of sleepiness
      (Karolinska Sleepiness Scale and simple serial reaction time test) and sleep
      (diary and actigraphy). RESULTS: Both subjective and objective measures improved
      gradually during night work. The return to day work after 1 week on the night
      shift led to a clear increase in subjective sleepiness and worsening of sleep
      parameters. During the week on the day shift, sleepiness and sleep gradually
      improved, similar to the improvement seen during night work. The workers
      indicated that the day shift was worse than the night shift on some of the
      measures, e.g., sleep length was significantly longer during the night-shift
      period. CONCLUSIONS: This is one of few studies showing how shift workers in a
      real-life setting adjust to night work. Both subjective and objective sleepiness
      and subjective sleep improved across days. The effects were especially pronounced
      for the subjective data.

PMID- 16796222
TI  - A brief afternoon nap following nocturnal sleep restriction: which nap duration
      is most recuperative?
AB  - STUDY OBJECTIVES: The purposes of this study were to compare the benefits of
      different length naps relative to no nap and to analyze the
      electroencephalographic elements that may account for the benefits. DESIGN: A
      repeated-measures design included 5 experimental conditions: a no-nap control and
      naps of precisely 5, 10, 20, and 30 minutes of sleep. SETTING: Nocturnal sleep
      restricted to about 5 hours in participants' homes was followed by afternoon naps
      at 3:00 PM and 3 hours of postnap testing conducted in a controlled laboratory
      environment. PARTICIPANTS: Twenty-four healthy, young adults who were good
      sleepers and not regular nappers. MEASUREMENTS AND RESULTS: The 5-minute nap
      produced few benefits in comparison with the no-nap control. The 10-minute nap
      produced immediate improvements in all outcome measures (including sleep latency,
      subjective sleepiness, fatigue, vigor, and cognitive performance), with some of
      these benefits maintained for as long as 155 minutes. The 20-minute nap was
      associated with improvements emerging 35 minutes after napping and lasting up to
      125 minutes after napping. The 30-minute nap produced a period of impaired
      alertness and performance immediately after napping, indicative of sleep inertia,
      followed by improvements lasting up to 155 minutes after the nap. CONCLUSIONS:
      These findings suggest that the 10-minute nap was overall the most effective
      afternoon nap duration of the nap lengths examined in this study. The
      implications from these results also suggest a need to consider a process
      occurring in the first 10 minutes of sleep that may account for the benefits
      associated with brief naps.

PMID- 16796224
TI  - Zolpidem tartrate use as contributory factor in sinus disease.

PMID- 16796223
TI  - The effects of caffeine, dextroamphetamine, and modafinil on humor appreciation
      during sleep deprivation.
AB  - STUDY OBJECTIVES: Sleep loss consistently impairs performance on measures of
      alertness, vigilance, and response speed, but its effects on higher-order
      executive functions are not well delineated. Similarly, whereas deficits in
      arousal and vigilance can be temporarily countered by the use of several
      different stimulant medications, it is not clear how these compounds affect
      complex cognitive processes in sleep-deprived individuals. DESIGN: We evaluated
      the effects of double-blind administration of 3 stimulant medications or placebo
      on the ability to appreciate humor in visual (cartoons) or verbal (headlines)
      stimuli presented on a computer screen following 49.5 hours of sleep deprivation.
      SETTING: In-residence sleep-laboratory facility at the Walter Reed Army Institute
      of Research. PARTICIPANTS: Fifty-four healthy adults (29 men, 24 women), ranging
      in age from 18 to 36 years. INTERVENTIONS: Each participant was randomly assigned
      to 1 of 3 stimulant medication groups, including caffeine, 600 mg, n = 12;
      modafinil, 400 mg, n = 11; dextroamphetamine, 20 mg, n = 16; or placebo, n = 14.
      MEASUREMENTS AND RESULTS: Humor appreciation for cartoon stimuli was enhanced by
      modafinil relative to both placebo and caffeine, but there was no effect of any
      stimulant medication on the appreciation of verbal humor during sleep loss. In
      contrast, all 3 stimulants improved psychomotor response speed, whereas only
      caffeine and dextroamphetamine improved ratings of subjective sleepiness.
      CONCLUSIONS: Findings suggest that, despite similar alerting and vigilance
      promoting effects, these 3 compounds have significantly different effects on
      those highly complex cognitive abilities mediated by the pre-frontal cortex.

PMID- 16796225
TI  - On the road to RHIOs.

PMID- 16796226
TI  - Passing the "Yo' Mama" test. Atlanta healthcare organization follows the beat of
      a different drummer in achieving 100 percent CPOE adoption.

PMID- 16796227
TI  - A season of change. One of the nation's most respected, well-established medical
      universities prepares to institute the next step in their PACS development-
      persona-based displays.

PMID- 16796228
TI  - Implementing EHRs requires a shift in thinking. PHRs--the building blocks of EHRs
      -may be the quickest path to the fulfillment of disease management.

PMID- 16796229
TI  - Information technology may not be 'it' for patient safety. Processes outweigh
      computers in improving quality.
AB  - While there is no question that information technology (IT) is inextricably tied
      to the future of health care delivery, claims that it is the cure-all for patient
      safety may be overrated. The key to success is managing change in organizational
      processes.

PMID- 16796230
TI  - Disaster preparedness: hospitals confront the challenge. Lessons learned from
      Oklahoma City and Manhattan provide national guidance.

PMID- 16796231
TI  - Trustee workbook 1. Trustee and board certification: A future trend?

PMID- 16796232
TI  - Keeping unions at bay. Rules and policies are a hospital's best defense against
      union infiltration.

PMID- 16796233
TI  - Consumer demands are changing care delivery.

PMID- 16796234
TI  - No clinician is an island.

PMID- 16796235
TI  - Establishing principles for hospital-physician joint ventures.

PMID- 16796236
TI  - Ask Jeeves: concierge services for hospitals.

PMID- 16796237
TI  - Rehabilitation Medicine Summit: Building Research Capacity--executive summary.
AB  - The advancement of medical science depends on the production, availability, and
      utilization of new information generated by research. A successful research
      enterprise depends not only on a carefully designed agenda that responds to
      clinical and societal needs but also on the research capacity necessary to
      perform the work. Research that is likely to enhance clinical practice
      presupposes the existence of a critical mass of investigators working as teams in
      supportive environments. Unfortunately, far too little research capacity of that
      kind exists in rehabilitation medicine to ensure a robust future for the field.
      The "Rehabilitation Medicine Summit: Building Research Capacity" was
      conceptualized as a way of fashioning a long-term plan to foster the required
      developments.

PMID- 16796238
TI  - Evaluation of a redesigned self-checkout station for wheelchair users.
AB  - Self-checkout is the emergent/emerging retail technology wherein users (shoppers)
      check out their own items using an interactive kiosk. A dramatic growth is
      anticipated in the prevalence of self-checkout systems in retail environments. A
      study was conducted to develop and evaluate a redesign of a self-checkout system
      with a focus on issues related to physical accessibility for wheelchair users.
      Two checkout station prototypes were built: a full-scale model of an existing
      system and a full-scale model of a system with design modifications (e.g.,
      inclusion of appropriate wheelchair clearance under the workstation, reduced
      vertical position of the credit card reader, etc.). Five wheelchair users and 10
      non-wheelchair users performed simulated self-checkout activities using both
      workstations. The principal independent variable was workstation type (standard
      design vs. modified design). The dependent measures were productivity (time to
      complete a transaction), shoulder flexion angle, torso flexion angle, and the
      user's subjective assessment of the experience. The results of this study
      indicate that workstation type did not influence productivity levels in either
      participant group (wheelchair users or non-wheelchair users). Posture, on the
      other hand, was significantly improved: the peak shoulder angle was reduced by
      64% in wheelchair users and by 69% in the non-wheelchair user group. Peak flexion
      angle of the torso was also reduced by 67% for wheelchair users. Subjective
      feedback from the wheelchair user group supported the postural data by showing an
      overall preference for the redesigned workstation, whereas the non-wheelchair
      group showed no preference between the two. These results indicate that design
      for populations with specific limitations does not need to come at a cost of
      reduced accessibility for persons without these limitations; universal design is
      achievable.

PMID- 16796239
TI  - The validity and applicability of the Chinese version of the Quebec User
      Evaluation of Satisfaction With Assistive Technology for people with spinal cord
      injury.
AB  - The Quebec User Evaluation With Assistive Technology (Version 2.0; QUEST 2.0) has
      become an important outcome assessment to capture user satisfaction in the field
      of assistive technology. The purpose of this study is to investigate the
      psychometric properties of the Chinese version of the QUEST 2.0 (C-QUEST) in
      terms of content and substantive and factor validity and to explore its
      applicability on user satisfaction on mobility and equipment among Chinese people
      with spinal cord injury. A group of six expert members were invited to evaluate
      the content validity and translation quality of the 12-item C-QUEST. The revised
      version, along with the brief version of the World Health Organization Quality of
      Life Questionnaire (WHOQOL-BREF [HK]), was administered on user satisfaction of
      people with spinal cord injury in the community. The content validity and item
      performance were evaluated to be satisfactory. Exploratory factor analysis with
      varimax rotation agreed with the bidimensional structure of Device and Services
      in the construct of user satisfaction (61.06% variance explained). Items in
      WHOQOL-BREF (HK) were shown to have positive and moderate correlations with C
      QUEST Device items (r = .412-.567, p < .05) but no significant associations with
      the Services items (p > .05). The 12-item C-QUEST was shown to be a valid and
      relevant instrument to capture the user satisfaction among Chinese people with
      spinal cord injury in the context of mobility and seating equipment.

PMID- 16796240
TI  - Accessible microscopy workstation for students and scientists with mobility
      impairments.
AB  - An integrated accessible microscopy workstation was designed and developed to
      allow persons with mobility impairments to control all aspects of light
      microscopy with minimal human assistance. This system, named AccessScope, is
      capable of performing brightfield and fluorescence microscopy, image analysis,
      and tissue morphometry requisite for undergraduate science courses to graduate
      level research. An accessible microscope is necessary for students and scientists
      with mobility impairments to be able to use a microscope independently to better
      understand microscopical imaging concepts and cell biology. This knowledge is not
      always apparent by simply viewing a catalog of histological images. The ability
      to operate a microscope independently eliminates the need to hire an assistant or
      rely on a classmate and permits one to take practical laboratory examinations by
      oneself. Independent microscope handling is also crucial for graduate students
      and scientists with disabilities to perform scientific research. By making a
      personal computer as the user interface for controlling AccessScope functions,
      different upper limb mobility impairments could be accommodated by using various
      computer input devices and assistive technology software. Participants with a
      range of upper limb mobility impairments evaluated the prototype microscopy
      workstation. They were able to control all microscopy functions including loading
      different slides without assistance.

PMID- 16796241
TI  - Prediction of calf volume during muscle contraction.
AB  - This study evaluated the relationship between calf volume changes and different
      intensities of maximum voluntary contractions (MVCs) of a lower limb performing
      plantar flexions. An electronic plethysmography instrument (EPI) was developed,
      and after testing for its reliability, it was used to measure calf volume
      changes. For EPI, the reliability correlation coefficients (r) to measure calf
      volume consistently were .98, .91, and .98 at 100% MVC, 80% MVC, and 60% MVC,
      respectively. There were also significant correlations between calf volume
      changes and the different intensities of MVC (MVC: r = .42, p < .011; 80% MVC: r
      = .41, p < .013; 60% MVC: r = .5, p < .002). The calf volume changes at different
      levels of muscle contractions also correlate significantly (upper calf: r = .55,
      p < .0002; middle calf: r = .58, p < .0007; and lower calf: r = .55, p < .002).
      The results indicated that EPI might be used as a reliable tool to predict the
      intensity of muscle contraction based on calf volume changes. Clinicians who use
      functional electrical stimulation to induce muscle contraction in people with
      muscle paralysis may use EPI to predict the volume changes during functional
      electrical stimulation-induced contractions and to deliver the proper amount of
      electrical stimulation, producing the desired level of contraction without undue
      stimulation or fatigue.

PMID- 16796242
TI  - Factors that influence the performance of experienced speech recognition users.
AB  - Performance on automatic speech recognition (ASR) systems for users with physical
      disabilities varies widely between individuals. The goal of this study was to
      discover some key factors that account for that variation. Using data from 23
      experienced ASR users with physical disabilities, the effect of 20 different
      independent variables on recognition accuracy and text entry rate with ASR was
      measured using bivariate and multivariate analyses. The results show that use of
      appropriate correction strategies had the strongest influence on user performance
      with ASR. The amount of time the user spent on his or her computer, the user's
      manual typing speed, and the speed with which the ASR system recognized speech
      were all positively associated with better performance. The amount or perceived
      adequacy of ASR training did not have a significant impact on performance for
      this user group.

PMID- 16796243
TI  - Sources of payment for assistive technology: findings from a national survey of
      persons with disabilities.
AB  - This article provides an overview of who pays for the most commonly used
      assistive technology devices, special adaptations, and environmental
      accommodations by persons with disabilities in the United States. The latest
      findings from the 2001 survey of Use and Need of Assistive Technology and
      Information Technology by Persons With Disabilities in the United States
      conducted by the National Institute on Disability and Rehabilitation Research,
      Rehabilitation Engineering and Assistive Technology Society of North America, and
      the University of Michigan will be presented and compared to findings from
      earlier research and reviews of the literature. A modified discriminant function
      analysis was performed to determine the interaction between the source of payment
      for assistive technology used by persons with disabilities. In the sample of
      1,414 such persons, 901 were found to use some form of assistive technology in
      their daily lives. Ten distinct sources of payment were specified. Respondents
      were able to mention up to three sources of payment for each example of assistive
      technology used. A total of 1,877 sources were mentioned. Overall, the most
      mentioned payment source was self or other family member in household, accounting
      for nearly 40% of all sources mentioned. The variables tested were found to have
      varying levels of interactive potency. Occupational status, education level,
      severity of impairment, opinion as to the effectiveness of assistive technology,
      and personal income were significant, whereas age, family income, opinion as to
      improvement over the past decade, and race were statistically unrelated to source
      of payment. From the perspective of relative discrimination on the basis of
      payment source, Medicare stands as the lone significant discriminant source of
      payment. The authors offer a summary and conclusion based on an integrated view
      of all available sources of information about payment.

PMID- 16796244
TI  - The Independent LifeStyle Assistant: lessons learned.
AB  - The Independent LifeStyle Assistant (I.L.S.A.) is an agent-based monitoring and
      support system to help elderly people live longer in their homes by reducing
      caregiver burden. I.L.S.A. is a multiagent system that incorporates a unified
      sensing model, situation assessments, response planning, real-time responses, and
      machine learning. This paper describes the six-month study of the system we
      fielded in elders' homes and the major lessons we learned during development.

PMID- 16796245
TI  - The development of an automated method for analyzing communication rate in
      augmentative and alternative communication.
AB  - A significant barrier to evidence-based practice in Augmentative and Alternative
      Communication (AAC) is the lack of validated performance measures that can be
      used by speech-language pathologists and rehabilitation engineers to evaluate the
      communication and device use of AAC consumers. Recently an effort has been made
      to develop automated data-logging techniques to facilitate the transcription and
      analysis of the AAC speaker's device use. A major source of error for the
      automated measurement of communication rate is the presence of excessive Inter
      Selection Intervals (ISIs) (i.e., pause times), for which no communicative
      activity is occurring. The goal of this study was to develop an automated
      technique to filter out extreme ISIs, while preserving true communication rate
      performance. AAC data log files were obtained from seven individuals
      participating in a 1-month field trial of an AAC technology. Two temporal
      filtering techniques (arbitrary and individual) were compared for their ability
      to eliminate excessive ISIs. Results indicated that use of an individualized
      temporal filter was more sensitive to performance variability than use of an
      arbitrary temporal filter. Further, the individualized temporal filter elevated
      the participants' communication rate (measured by words per minute) by a factor
      of 1.8 to 34.5 greater than that of the unfiltered communication rate estimate.
      In addition, the first AAC communication rate performance estimates taken from
      the field are presented. Implications for further research and the valid use of
      automated data logging and analysis are discussed.

PMID- 16796246
TI  - Working together.

PMID- 16796247
TI  - It's hard to cry!

PMID- 16796248
TI  - Planning for the next pandemic.

PMID- 16796249
TI  - TeamHealth mistaken for HealthSouth in Katrina editorial.

PMID- 16796250
TI  - Knox County Katrina response "not perfect" but an overall success.

PMID- 16796251
TI  - Emergency care in Tennessee headed for a breakdown.

PMID- 16796252
TI  - Medical records ownership.

PMID- 16796253
TI  - Charles R. Handorf, MD, PhD--An interview with TMA's 152nd president. Interview
      by Victor J Carrozza.

PMID- 16796254
TI  - Cover Tennessee--long on promise, short on detail.

PMID- 16796255
TI  - MLR: where do we go from here?

PMID- 16796256
TI  - How on earth did this happen?

PMID- 16796257
TI  - HIPAA regs update: myths and misconceptions.

PMID- 16796258
TI  - When can I safely retire?

PMID- 16796259
TI  - Ageism in breast cancer surgical options by medical students.
AB  - INTRODUCTION: The similar long-term survival of breast conservation and modified
      radical mastectomy in treating early invasive breast cancer has been well
      established. Since doctors often find themselves in the position of making
      operative recommendations, characterization of factors that may influence their
      recommendations is important. Previous investigations have demonstrated the
      phenomenon of ageism (i.e., between patients aged 30 versus 60 years old) in
      doctors and doctors-in-training. Thus, this study was undertaken to investigate
      any possible economic bias of doctors-in-training in breast conserving
      procedures. METHODS: Medical students were instructed on the efficacy of breast
      conservation in treating breast cancer. Then, their opinions were assessed using
      a questionnaire about recommendations for breast conservation as well as breast
      reconstruction after mastectomies in similar patients. All patients were between
      the ages of 41-54 years old but differed by occupation. Chi squared tests were
      used for statistical analysis. RESULTS: Forty-eight students participated in the
      study. No differences were noted between "high income" occupations and "low
      income" occupations. However, subtle ageism was noted even in this similarly aged
      population. Modified radical mastectomy was recommended in 35 percent of the
      "older" age group (41-48 years old) versus 15 percent of "younger" patients (49
      54 years old, p < 0.002). Further, breast reconstruction was recommended in 89
      percent of younger patients versus only 72 percent of older patients (p < 0.004).
      CONCLUSIONS: Medical students still demonstrate an age bias against older women
      in their recommendations of breast conservation and breast reconstruction.
      Educational efforts should be instituted during the medical school training to
      decrease this age bias in treatment of breast cancer.

PMID- 16796260
TI  - Liability for outpatient suicide in Tennessee.

PMID- 16796261
TI  - History of Tennessee Medicine, Part IV. Dr. Currey on iron, 1840.

PMID- 16796262
TI  - Read the fine print.

PMID- 16796263
TI  - Triage system blamed for treatment delays.

PMID- 16796264
TI  - Nurses speak out on National Nurses Week.

PMID- 16796265
TI  - Sending a lifeline across the sea.

PMID- 16796266
TI  - Inserting an NG tube.

PMID- 16796267
TI  - Putting your patient ed to the test.

PMID- 16796268
TI  - Follow these steps when appealing a Medicare claim.

PMID- 16796269
TI  - Stop the assault on skin in HIV.

PMID- 16796270
TI  - Patient information. Skin care tips for patients with HIV.

PMID- 16796271
TI  - Drug watch 2006: cancer therapies.

PMID- 16796272
TI  - Depression in the elderly.

PMID- 16796273
TI  - The dysphagia dilemma: how you can help.

PMID- 16796274
TI  - RV living for travelers.

PMID- 16796275
TI  - Don't blame the shortage!

PMID- 16796276
TI  - Safety of oral bisphosphonates: controlled studies on alveolar bone.
AB  - PURPOSE: Osteoporosis and osteopenia are characterized by reductions in bone mass
      and may lead to skeletal fragility and fracture. The latest generation of oral
      bisphosphonate drugs, including alendronate and risendronate, has been approved
      for the prevention and treatment of osteoporosis. These medications are
      chemically absorbed into bone, decreasing osteoclast number and activity and
      thereby decreasing bone resorption. The purpose of this report is to present
      safety data from 2 controlled studies in patients receiving oral bisphosphonates.
      MATERIALS AND METHODS: Study 1 tested the effect of alendronate, an inhibitor of
      bone resorption, on alveolar bone. A total of 335 patients (162 men and 173
      women, aged 30 to 79 years) with moderate or severe periodontal disease were
      randomized to either placebo or 70 mg alendronate once weekly. Alveolar bone
      height and safety were assessed over a 2-year period. Study 2 was a longitudinal
      single-blind controlled design comparing implant success in 50 consecutive
      patients (210 implants), 25 patients who received bisphosphonate therapy and 25
      age-matched control subjects. Implant success and safety, including incidence of
      osteonecrosis of the jaws (ONJ), was blindly assessed for at least 3 years.
      RESULTS: In study 1, no cases of ONJ were observed in either treatment group.
      Furthermore, a trend toward lower incidences of infection and tooth loss was
      observed in the alendronate group. In study 2, no cases of ONJ were observed in
      either group, and implant success was greater than 99% in both groups.
      CONCLUSION: On the basis of 2 controlled clinical studies, oral bisphosphonate
      usage was not associated with occurrence of ONJ.

PMID- 16796277
TI  - Effects of surface topography on the connective tissue attachment to subcutaneous
      implants.
AB  - PURPOSE: A major concern for implants that penetrate stratified epithelia is
      aggressive epithelial proliferation and migration. This epithelial downgrowth on
      the implant can be inhibited by a firm attachment between the underlying
      connective tissue and the implant. This study evaluates the connective tissue
      attachment to titanium implants with various well-defined surface topographies.
      MATERIALS AND METHODS: Titanium-coated epoxy replicas of polished (PO; R(a) =
      0.06 microm), finely blasted (FB; R(a) = 1.36 microm), coarsely blasted (CB; R(a)
      = 5.09 microm), acid-etched (AE; R(a) = 0.59 microm), coarsely blasted and acid
      etched (SLA; R(a) = 4.39 microm), titanium plasma-sprayed (TPS; R(a) = 5.85
      microm), machined-like (ML; R(a) = 2.15 microm), and micromachined grooved (GR; V
      shaped grooves 30 microm deep) surfaces were implanted subcutaneously in 74 rats
      for 1 to 11 weeks. Animals were sacrificed weekly. Surfaces were processed for
      histomorphometric evaluation of connective tissue attachment, capsule thickness,
      and where applicable, the degree of separation between the tissue and implant.
      RESULTS: A total of 153 test surfaces were analyzed. Statistical analysis
      revealed that textured and rough substrata, namely the GR, TPS, AE, CB, and SLA
      surfaces, exhibited significantly greater (P < .05) connective tissue attachment
      and thinner fibrous encapsulation when compared to the PO surface. Tissue
      separation from the implant interface was of significantly lower magnitude and
      frequency with the rough surfaces than with the PO surface. CONCLUSIONS: The
      results indicate that rough implant surfaces are associated with stable
      connective tissue attachment, which has implications for their use in
      percutaneous and permucosal applications. In addition, data from the AE surface
      may indicate that the geometry of the surface irregularities can also be a
      significant determinant of the connective tissue response.

PMID- 16796278
TI  - Maxillary sinus augmentation as a risk factor for implant failure.
AB  - PURPOSE: The investigators sought to determine whether maxillary sinus
      augmentation (MSA) was an independent risk factor for implant failure. MATERIALS
      AND METHODS: Using a retrospective cohort study design, the investigators
      enrolled a sample composed of subjects having 1 or more implants placed in the
      posterior maxilla. The primary predictor variable was MSA status at the time of
      implant placement (MSA present or absent). MSA consisted of a lateral window
      (external) or an osteotome (internal) procedure. The outcome variable was implant
      failure defined as implant removal. Demographic, health status, anatomic, implant
      specific, abutment-specific, prosthetic, and perioperative variables were also
      examined. Overall implant survival was estimated using Kaplan-Meier analysis.
      Risk factors for implant failure were identified using Cox proportional hazard
      regression models. RESULTS: The sample consisted of 318 patients and 762
      posterior maxillary implants. The mean duration of follow-up was 22.50 +/- 19.06
      months. The 5-year survival rates for implants in the ungrafted and grafted
      posterior maxilla were 88.0% and 87.9%, respectively (P = .08). After adjustment
      for covariates, MSA status was not an independent risk factor for implant failure
      (P = .9). Tobacco use (P < .001), implants replacing molars (P < .001), and 1
      stage implants (P < .001) were statistically associated with an increased risk
      for implant failure. DISCUSSION: MSA status was not associated with implant
      failure risk. This finding may be subject to selection bias, as successful MSA
      was requisite prior to implant placement. CONCLUSION: MSA status was not
      associated with an increased risk for implant failure. Of the 3 factors
      associated with an increased risk for failure, tobacco use and implant staging
      may be modified by the clinician to enhance outcome.

PMID- 16796279
TI  - Use of Er:YAG laser to improve osseointegration of titanium alloy implants--a
      comparison of bone healing.
AB  - PURPOSE: The objective of this study was to compare the osseointegration of
      implants in rats in sites prepared with an Er:YAG laser with osseointegration in
      sites prepared using a conventional drill by assessing the percentage of bone
      implant contact (BIC). MATERIALS AND METHODS: Osteotomies were prepared with an
      Er:YAG laser in the tibiae of 18 rats (the test group) and drill-prepared with a
      1.3-mm-wide surgical implant drill at 1,000 rpm with simultaneous saline
      irrigation in the tibiae of another 18 rats (the control group). Acid-etched
      titanium alloy implants (2 x 8 mm) were placed in the tibiae, engaging the
      opposite cortical plate. The Er:YAG laser was used with a regular handpiece and
      water irrigation (spot size, 2 mm; energy per pulse, 500 to 1,000 mJ; pulse
      duration, 400 ms; and energy density, 32 J/cm2). Nine animals from each group
      were sacrificed after 3 weeks of unloaded healing; the remainder were sacrificed
      after 3 months. The tissues were fixed and prepared for histologic and
      histomorphometric evaluation. RESULTS: Statistical analysis showed significant
      differences between the 2 groups at both 3 weeks and 3 months. After 3 weeks of
      unloaded healing, the mean BICs (+/- SD) were 59.48% (+/- 21.89%) for the laser
      group and 12.85% (+/- 11.13%) for the control group. Following 3 months of
      unloaded healing, the mean BICs (+/- SD) were 73.54% (+/- 11.53%) for the laser
      group and 32.6% (+/- 6.39%) for the control group. DISCUSSION: Preparation of the
      implant sites with the Er:YAG laser did not damage the interface; the healing
      patterns presented were excellent. CONCLUSIONS: Based on the results of this
      study, it may be concluded that the Er:YAG laser may be used clinically for
      implant site preparation with good osseointegration results and bone healing and
      with a significantly higher percentage of BIC compared to those achieved with
      conventional methods.

PMID- 16796280
TI  - Consolidation period in alveolar distraction: a pilot histomorphometric study in
      the mandible of the beagle dog.
AB  - PURPOSE: Osteogenic alveolar distraction remains in an experimental stage. The
      present study aimed to compare histologic and histomorphometric results with 2
      different consolidation periods (4 and 8 weeks) to determine which period
      obtained better bone quality after distraction with a prototype alveolar
      distractor. MATERIALS AND METHODS: Five beagle dogs were used. Four underwent
      alveolar distraction in an edentulous segment of the right mandible. After a 7
      day latency period, distraction was carried out at a rate of 1 mm/d for 5 days;
      the consolidation period was 4 weeks in 2 dogs (group 1), and 8 weeks in the
      other 2 (group 2). The fifth dog was used as control (group 3); it underwent
      removal of its right premolars but not distraction. Histologic and
      histomorphometric studies were conducted. RESULTS: One animal from each
      distraction group was withdrawn from the study because of wound dehiscence that
      allowed invasion of mucosa into the distraction chamber, which was incompatible
      with bone regeneration. In the group 1 animal, a predominance of immature woven
      bone was observed in the distraction chamber, whereas the group 2 animal showed a
      predominance of immature parallel-fibered bone. The group 1 and 2 animals that
      remained in the study differed in bone area density in the distraction chamber
      (36.61% +/- 9.79% versus 58.72% +/- 8.30%), bone perimeter in the distraction
      chamber (262.89 +/- 10.46 mm versus 201.44 +/- 22.64 mm), total height attained
      (21.31 +/- 0.32 mm versus 18.37 +/- 0.50 mm), lingual trabecular width (134.00 +/
      15.56 versus 229.50 +/- 29.24), buccal trabecular width (90.00 +/- 4.24 mm
      versus 154.50 +/- 21.64 mm), lingual osteoid area density (4.08% +/- 0.46% versus
      1.61% +/- 0.33%), and buccal osteoid area density (3.75% +/- 1.28% versus 2.09%
      +/- 0.79%). CONCLUSION: Quantitative and qualitative differences in newly formed
      bone were observed after 4 and 8 weeks of consolidation. These preliminary
      results serve as a basis for further experimental research with larger samples
      and for clinical studies.

PMID- 16796281
TI  - Histomorphometric evaluation and clinical assessment of endosseous implants in
      iliac bone grafts with shortened healing periods.
AB  - PURPOSE: In the present study solid monocortical hipbone onlay grafts of the
      maxilla were analyzed histologically after a healing period of 3 months. The
      clinical success of the implants placed in the grafted bone was evaluated.
      MATERIALS AND METHODS: Nineteen patients underwent augmentation with avascular
      iliac bone. A 2-stage procedure was performed with a 3-month healing period
      between graft and implant placement. At implant placement bone biopsy samples
      were taken at the proposed implant sites. RESULTS: Of the 117 implants placed, 1
      was not osseointegrated at the time of abutment connection. No implants were lost
      after loading during an observation period of up to 3 years. Clinical appearance
      of the augmented bone after 3 months showed a dense cortical layer with good
      blood perfusion. Histologic specimens were analyzed quantitatively and showed an
      average of 43.2% newly formed bone. DISCUSSION: Histomorphometry showed that the
      amount of newly formed bone after 3 months was comparable to that found after a
      healing period of 4.5 months. The clinical success of the implants placed after
      the shortened healing period was comparable to that found in nonaugmented bone.
      CONCLUSION: This study showed that after avascular iliac bone grafting, 3 months
      of revascularization was sufficient to ensure the secure placement of dental
      implants in second-stage surgery for this patient population.

PMID- 16796282
TI  - Rehabilitation of severely resorbed maxillae with zygomatic implants: an
      evaluation of implant stability, tissue conditions, and patients' opinion before
      and after treatment.
AB  - PURPOSE: The aim of the present study was to describe experiences of 11
      consecutively treated patients who received zygomatic implants. Patient results
      were assessed through clinical and radiographic evaluations of tissue conditions,
      including resonance frequency analysis (RFA). MATERIALS AND METHODS: Eleven
      patients were treated with implant-retained fixed prostheses. A total of 64
      implants were placed, 22 of which were placed in the zygoma. Fixed prostheses
      were removed to allow clinical and radiographic evaluations at a follow-up visit
      18 to 46 months following implant placement. RFA was performed on all implants. A
      visual analog scale was used to assess patient satisfaction before and after
      treatment. RESULTS: All patients received implant-supported prostheses. All
      zygomatic implants demonstrated clinical signs of osseointegration. One anterior
      implant was lost during follow-up. Mean ISQ values for the zygomatic and anterior
      implants were 65.9 (range, 42 to 100) and 61.5 (range, 48 to 71), respectively.
      Twenty-four implants showed moderate inflammation, with 3 exhibiting severe
      inflammation. Most anterior implants (75.6%) showed a marginal bone recession of
      1 thread or less. Four zygomatic implants showed bone loss of 4 to 5 threads, and
      5 zygomatic implants exhibited no marginal bone support. Patients described
      significant improvement in chewing ability and esthetics but did not describe
      changes in speech. DISCUSSION: The use of zygomatic implants can help the
      clinician avoid the need for bone grafting and reduce morbidity. In addition, it
      can shorten the treatment time considerably. CONCLUSION: This preliminary report
      demonstrates that zygomatic implants can provide posterior support to fixed
      prostheses in patients who lack bone volume to place conventional implants
      without encroaching upon the maxillary sinus.

PMID- 16796283
TI  - A retrospective analysis of peri-implant tissue responses at immediate
      load/provisionalized microthreaded implants.
AB  - PURPOSE: The aim of this retrospective study was to examine the peri-implant
      tissue status at immediately provisionalized anterior maxillary implants 12 to 30
      months following tooth replacement. MATERIALS AND METHODS: This is a
      retrospective study of 43 microthreaded, TiO2 grit-blasted implants placed in
      healed ridges and immediate extraction sockets to restore maxillary anterior and
      premolar teeth in 28 patients. The cortical bone position relative to the implant
      reference point was evaluated at implant placement and 6 to 30 months following
      restoration. Radiographs were assessed using 7x magnification. The distance from
      the reference point to the cortical bone was measured to +/- 0.1 mm. The
      relationship of the peri-implant mucosa to the incisal edge of the definitive
      prosthesis was recorded. RESULTS: Four implants in 3 individuals failed during
      the first 6 weeks following placement and provisional loading. Cortical bone
      adaptation from the time of implant placement up to 30 months following
      restoration ranged from 0.0 mm to 1.5 mm (average, 0.33 +/- 0.40 mm mesially and
      0.28 +/- 0.37 mm distally). The mean radiographic measurements from the
      interproximal crestal bone to the contact point were 4.53 +/- -0.91 mm (mesial)
      and 4.06 +/- 0.98. Maintenance and growth of papilla was observed in this group
      of immediate provisionalized single-tooth implants. Definitive abutment or
      abutment screw loosening was not observed. DISCUSSION: The linear clinical and
      radiographic measures of peri-implant tissue responses suggest that proper
      implant placement is followed by supracrestal biological width formation along
      the abutment and preservation of toothlike tissue contours. This may influence
      buccal peri-implant tissue dimensions. CONCLUSIONS: Generalized maintenance of
      crestal bone and the increased soft tissue dimension with maintenance of peri
      implant papilla were identified as expected outcomes for immediate
      loading/provisionalization of microthreaded, TiO2 grit-blasted implants. Control
      of peri-implant tissues can be achieved to provide predictable and esthetic
      treatment for anterior tooth replacement using dental implants.

PMID- 16796284
TI  - Survival rate of zygomatic implants in atrophic or partially resected maxillae
      prior to functional loading: a retrospective clinical report.
AB  - PURPOSE: The purpose of this article was to evaluate the survival rate of 34
      remote anchorage implants placed in 18 patients from placement to uncovering,
      prior to any prosthetic loading. MATERIALS AND METHODS: A total of 18 patients (9
      women and 9 men with a mean age of 63 years) who required rehabilitation with a
      fixed prosthesis because of severely atrophic maxillae (including 1 patient who
      had undergone primary and secondary cleft lip and palate repair), traumatic
      maxillary bone loss, and maxillectomy procedures received 1 or 2 zygomatic
      implants and 2 to 4 standard maxillary dental implants. The survival rate of the
      34 zygomatic implants from placement to uncovering was investigated. Aspects of
      the placement technique or postoperative complications related to surgical
      procedures likely to affect the implant failure rate were detected and critically
      discussed. RESULTS: Osseointegration was evaluated using the reverse torque test
      and percussion after uncovering. Only 1 patient (5.6%) sustained postoperative
      clinical complications during the evaluation period which resulted in the loss of
      both zygomatic implants (5.9%). CONCLUSION: Although the handling of this
      anchorage implant system is somewhat complex, and the design has certain
      shortcomings, it might be an alternative to more extensive bone augmentation
      procedures. However, rehabilitation of partially or completely edentulous
      patients with fixed implant-supported prosthesis is only feasible when 2 to 4
      standard implants are placed in the anterior maxilla and splinted with the
      zygomatic implants.

PMID- 16796285
TI  - A study of 25 zygomatic dental implants with 11 to 49 months' follow-up after
      loading.
AB  - PURPOSE: The purpose of this study was to evaluate indications, surgical
      problems, complications, and treatment outcomes related to the placement of
      zygomatic implants. A second aim was to determine any prosthetic difficulties and
      complications. MATERIALS AND METHODS: Twenty-five zygomatic implants were placed
      in 13 patients between April 1999 and December 2001. The patient age range was
      between 49 and 73 years, with a mean age of 59 years. All patients showed severe
      resorption of alveolar bone in the maxilla. All but 2 patients were smokers. Two
      patients had a history of cleft palate surgery, and 2 patients were known to be
      bruxers. Standard recommended surgical protocol was followed, and treatment was
      performed under general anesthesia. After abutment surgery, 9 patients received
      bar-retained overdentures, and 4 patients received fixed prostheses. RESULTS: No
      implants were lost, and few surgical complications were experienced. The follow
      up period was 11 to 49 months. DISCUSSION: Although surgical problems
      precipitated by difficult anatomy in cleft patients and a patient with reduced
      interarch access were experienced, the results were favorable. Fabricating a
      functional and esthetic prosthesis can be a challenge. CONCLUSION: Zygomatic
      implants provide a treatment option for patients with severe maxillary
      resorption, defects, or situations where previous implant treatment has failed.
      In this experience, treatment with zygomatic implants was a predictable method
      with few complications, even in a group of patients that would not be considered
      ideal for implant treatment.

PMID- 16796286
TI  - Sinus elevation with alloplasts or xenogenic materials and implants: an up-to-4
      year clinical and radiologic follow-up.
AB  - PURPOSE: The clinical and radiologic results of bone substitute application in
      the sinus elevation procedure were evaluated for up to 4 years after a grafting
      procedure followed by implant placement. MATERIALS AND METHODS: Between 1997 and
      2001, augmentation of the maxillary sinus floor with alloplastic or xenogenic
      materials was performed in 34 nonsmoking patients with generally good health.
      However, only 18 patients attended all of the required annual clinical and
      radiographic examinations and thus were included in the study. Mean follow-up
      after implantation was 29 months. RESULTS: At the second-stage surgery all the
      implants were osseointegrated, except for 1 Frialit-2, which was removed.
      Following prosthetic rehabilitation no implant was lost after 4 years of
      function, for a prosthetic success rate of 100%. The cumulative implant survival
      rate after 48 months was 97% (36 of 37 implants). DISCUSSION: Osseointegrated
      implants are a reliable treatment option for restoring the posterior maxilla, and
      final predictability was not influenced by their placement in augmented areas
      after sinus elevation with bone substitutes. CONCLUSIONS: The survival rate
      obtained with this study is similar to that expected for implants placed in
      nongrafted areas. This study showed that alloplasts and xenogenic materials are
      reliable for bone regeneration in the subantral cavities, as they showed very low
      resorption in the present study.

PMID- 16796287
TI  - Measurement of volume changes after sinus floor augmentation with a phycogenic
      hydroxyapatite.
AB  - PURPOSE: The purpose of this study was the determination of time-dependent
      volumetric changes of particulate sinus inlay grafts. A mixture of phycogenic
      hydroxyapatite (Algipore/C-Graft) and autologous bone collected from the surgical
      access area was used as the grafting material. MATERIALS AND METHODS: Thirty
      three sinus floor augmentations using phycogenic hydroxyapatite combined with
      autologous bone collected at the augmentation site and venous blood were
      performed on 18 patients aged 57.4 +/- 12.5 years (mean +/- SD) with severe
      atrophy of the posterior maxilla. Graft volume was measured 1 to 14 days
      postoperatively and before the placement of dental implants 6.1 +/- 2.1 months
      later (mean +/- SD; range, 4 to 11 months) to evaluate the amount of time
      dependent resorption of the implanted material on computerized tomographic (CT)
      images of the augmented region. The images were put into Digital Imaging and
      Communications in Medicine (DICOM) format and evaluated using the software
      library Analyze. The implanted bone replacement material was plotted manually on
      each CT slice, and the volume of the implanted material was calculated. RESULTS:
      The average volume loss of the bone replacement material during the observation
      period was 13.9% +/- 1.9% (mean +/- SEM). All sinus floor augmentations healed
      without complications except for delayed membrane exposure in 2 cases.
      DISCUSSION: The results indicate that the graft material, a mixture of Algipore,
      bone chips from the access area, and venous blood, exhibited a small volume loss
      over a period of approximately 6 months, thus providing predictable height for
      second-stage implant surgery. CONCLUSION: Further investigations are needed to
      evaluate long-term stability and implant success.

PMID- 16796288
TI  - Management of apical bone loss around a mandibular implant: a case report.
AB  - Various terms, etiologies, and treatment strategies have been suggested in
      conjunction with bone loss limited only to the apical portion of an implant that
      remains otherwise well osseointegrated. Proposed etiologic factors include bone
      overheating, microbial involvement of adjacent teeth, pre-existing bone
      infection, and overload. However, the mandible and maxilla seem to have different
      predispositions in response to these causative agents. Treatment protocols for
      peri-implant infection have included minimally invasive approaches such as
      granulation tissue removal and detoxification of the implant surface, as well as
      more aggressive measures. This case report demonstrates the achievement of
      osseous healing and reosseointegration in a patient who presented with presented
      apical bone loss and signs of infection around a mandibular implant.
      Reosseointegration was achieved following an intraoral apicoectomy-like approach,
      ie, removal of the infected nonintegrated portion of the implant, and meticulous
      debridement of the granulation tissue. A literature review of 13 relevant
      published studies was conducted. The current understandings regarding the
      etiology and treatment strategies for management of apical bone loss around
      dental implants are summarized and presented.

PMID- 16796289
TI  - Preliminary report on a staged ridge splitting technique for implant placement in
      the mandible: a technical note.
AB  - PURPOSE: Narrow edentulous alveolar ridges less than 5 mm wide require horizontal
      augmentation for the placement of screw-type dental implants. A staged approach
      to ridge splitting in the mandible to decrease the risk of malfracture during
      osteotomy is presented. MATERIALS AND METHODS: Five consecutive patients with 6
      long-span edentulous areas of the mandibular ridge were included in this study.
      After corticotomy of a rectangular buccal segment and a 40-day healing period,
      the mandibular ridge was split, leaving the buccal periosteum attached to the
      lateralized segment. Seventeen dental implants were placed, and the gap between
      the implants and the bone filled with a mixture of venous blood and a porous
      algae-derived hydroxyapatite. RESULTS: All buccal segments fractured as planned
      at the basal corticotomy during ridge splitting. After 6 months, all implants
      were stable and surrounded by bone; prosthetic loading with fixed partial
      dentures was successful in all cases. DISCUSSION: In the mandible, greenstick
      fracture during widening with osteotomes has not been controllable to date
      because of cortical thickness of the bone; the risk of malfracture during single
      stage ridge splitting was high. With this approach, the location of the
      greenstick fracture is predetermined, and the perfusion for the buccal segment
      remains intact, although vascularization shifts from internal perfusion from
      spongy bone after the first intervention to external perfusion from the
      periosteum after the second intervention. The buccal cortical segment remains a
      pedicled graft after ridge splitting. CONCLUSION: The preliminary results of this
      report indicate that staged ridge splitting can be a safe technique which
      overcomes the problems associated with single-stage ridge expansion/ridge
      splitting procedures without causing significant delay in treatment.

PMID- 16796290
TI  - Bone height measurements around a dental implant after a 6-month space flight: a
      case report.
AB  - PURPOSE: In space, astronauts are subject to microgravity, which reduces skeletal
      loading and osteoblast function and can cause bone resorption and a decrease in
      bone density. No known research to date has studied the effect of microgravity on
      dental implants. This study evaluated peri-implant bone changes around a dental
      implant placed in a French astronaut who spent 6 months in Russia's Mir Space
      Station. MATERIALS AND METHODS: Measurements were performed by 2 examiners before
      the flight (baseline), after the flight (stage 1), and following a recovery
      period (stage 2). Standardized periapical radiographs were taken, and data were
      recorded using a photomicroscope and a measuring scale. RESULTS: Cumulatively,
      the implant sustained 0.43 mm of mesial bone gain and 0.31 mm of distal bone
      loss. DISCUSSION: The observed peri-implant bone height changes were within
      normal limits and the implant appeared very stable during the course of this
      study. CONCLUSION: Peri-implant bone levels remained stable after 6 months in
      microgravity, and the implant continued to function without complications.

PMID- 16796291
TI  - The use of negative pressure for the sinus lift procedure: a technical note.
AB  - The objective of the present report was to present a modification of the standard
      sinus lift procedure. The modification consists of the creation of a mechanism
      facilitating maxillary sinus mucosa lift by means of negative pressure and
      simplification of the instrumentation used for this procedure. With the change in
      technique, maintenance of the success and predictability rates observed in the
      literature is possible.

PMID- 16796292
TI  - Oral rehabilitation of a patient with diffuse lymphangiomatosis affecting the
      maxilla: a case report.
AB  - A case is presented in which diffuse lymphangiomatosis resulted in the complete
      loss of the maxillary dentoalveolar complex and underlying basal bone. The
      complex investigation and treatment of this patient over a 10-year period is
      presented, and the importance of a multidisciplinary team approach in providing a
      functional and esthetic rehabilitation is highlighted. The use of a vascularized
      bone graft based on the deep circumflex iliac artery and subsequent restoration
      with an implant-supported prosthesis is described.

PMID- 16796293
TI  - Three-dimensional accuracy of implant placement in a computer-assisted navigation
      system.
AB  - PURPOSE: To evaluate the 3-dimensional accuracy of dental implant drilling in a
      computer-assisted navigation (CAN) system using simulated mandible models.
      MATERIALS AND METHODS: Eight acrylic resin models were fabricated to simulate
      human mandibles containing mandibular canal (MC). Computerized tomography (CT)
      scans were obtained for each model, and the data were transferred to the system
      for dental implant planning. The models were mounted on a phantom head to
      simulate surgical situation. The assessment parameters included entry point
      localization, drill path angulation, and drilling depth, which were directly
      measured by sectioning of the models. RESULTS: Eighty drill holes were made on
      the 8 models. The entry point localization showed a mean deviation of 0.43 mm
      (range, 0 to 2.23 mm; SD, 0.56 mm) from the plan. The angulation showed a mean
      deviation of 4.0 degrees (range, 0 to 13.6 degrees; SD, 3.5 degrees). The drill
      aimed at stopping as close to the upper border of the MC as possible without
      perforating it, and 65% (52) of the drill holes managed to come within 1 mm.
      Another 5% of the holes stopped 1 to 2 mm above the MC. None of the drill holes
      stopped more than 2 mm above the MC. However, 30% (24 of 80) of the drill holes
      perforated the upper border of MC, and the mean depth of perforation was 0.37 mm
      (range, 0.01 to 1.04 mm; SD, 0.28 mm). DISCUSSION AND CONCLUSION: The CAN system
      identified the entry location and angulation with mean deviations of 0.43 mm and
      4 degrees, respectively. About two thirds of the drillings achieved accuracy
      within 1 mm above the MC. Thirty percent perforated into the MC, and the maximal
      depth was 1.04 mm. In the planning stage, the maximal depth of the implant should
      be at least 1.1 mm above the superior border of MC as a safety margin.

PMID- 16796294
TI  - Repeated distraction osteogenesis for excessive vertical alveolar augmentation: a
      case report.
AB  - In this article, a procedure involving 2-stage alveolar distraction osteogenesis
      using eccentric distraction devices for the augmentation of resorbed transplanted
      iliac bone following mandibular tumor resection is presented. A 6-month
      consolidation period was allowed between the first and second distractions, and
      endosseous implants were placed 4 months after the second distraction.
      Computerized tomographic images obtained before the implantation revealed that,
      10 months after the first distraction, the bone generated still showed lower
      density compared with the basal bone, but the bone from both distractions showed
      enough maturity for implantation. It may be concluded that 2-stage alveolar
      distraction osteogenesis can be a useful and safe procedure for excessive
      alveolar lengthening if a sufficiently long consolidation period is allowed.

PMID- 16796295
TI  - Therapeutic management for immediate implant placement in sites with periapical
      deficiencies where coronal bone is present: technique and case report.
AB  - A surgical approach is presented that enables the clinician to repair apical bony
      defects during immediate dental implant placement without compromising the
      integrity of the coronal bone and gingiva. This apical surgical technique retains
      the soft tissue form in the coronal aspect of the gingiva and allows the
      clinician to repair the apical bone loss or fenestration. A clinical case is
      presented to describe the technique. This technique is utilized in cases of
      immediate implant placement. After extraction of the tooth, the socket is
      evaluated. In cases where coronal bone is intact but apical bone is deficient, a
      flap technique is utilized to expose the defect. The implant osteotomy is
      prepared, and the implant is placed. A healing cap or gingival prosthetic
      component is connected. The bony defect is repaired with a bone graft and, where
      necessary, a membrane. The apicoectomy flap is sutured. The clinical results
      obtained using this technique will enable the clinician to accomplish the bone
      regenerative procedure without extending the flap to the coronal aspect of the
      socket during immediate implant placement. This technique assists in the
      maintenance and integrity of the soft tissue form, which is critical for optimal
      esthetic results.

PMID- 16796296
TI  - Dental restoration with endosseous implants after mandibular reconstruction using
      a fibula free flap and TMJ prosthesis: a patient report.
AB  - This patient report describes the secondary reconstruction of a hemimandibular
      and condylar defect and the dental restoration of a 56-year-old woman who had
      been subjected to radical ablative surgery 30 years earlier to remove a tumor. In
      the first phase, a fibula free flap was used in combination with a total TMJ
      prosthesis for the reconstruction of the hemimandible and condyle. Secondly, 3
      endosseous implants were placed in the residual mandible. These implants were
      used to support an overdenture prosthesis that has remained in continuous
      function for a period of 2 years.

PMID- 16796297
TI  - Auditory processing disorders in children.

PMID- 16796298
TI  - The listening in spatialized noise test: an auditory processing disorder study.
AB  - The Listening in Spatialized Noise test (LISN) produces a virtual three
      dimensional auditory environment under headphones. Various measures assess the
      extent to which either spatial, vocal, or spatial and vocal cues combined
      increase a listener's ability to comprehend a target story in the presence of
      distracter sentences, without being affected by differences between participants
      in variables such as linguistic skills. Ten children at risk for auditory
      processing disorder (APD group) were assessed on the LISN, as well as a
      traditional APD test battery. The APD group performed significantly more poorly
      on all LISN measures than 48 age-matched controls. On the spatial advantage
      measure, the APD group achieved a mean advantage of only 3.7 dB when the
      distracters were spatially separated from the target by +/-90 degrees, compared
      to 10.0 dB for the controls-the 6.3 dB difference significant at p < 0.000001,
      with nine children scoring outside the normal range. The LISN was considered a
      promising addition to an APD test battery.

PMID- 16796299
TI  - A comparison of entrance and graduation requirements for the Au.D. with other
      first professional degrees.
AB  - Over the past several years there has been increasing reference to the Doctor of
      Audiology degree (Au.D.) as a "first professional degree." Currently, first
      professional degrees are awarded in the fields of chiropractic, dentistry, law,
      medicine, optometry, osteopathic medicine, pharmacy, podiatry, theology, and
      veterinary medicine. General entrance requirements, clinical experiences, and
      graduation requirements for the Au.D. degree were compared to the health-care
      professions awarding first professional degrees. Comparisons were also made to
      the professions of pharmacy, psychology and speech-language pathology. For all
      first professional degree occupations, unique entrance and competency examination
      processes have been developed. The four-year postbachelor's Au.D. degree model is
      similar in length to first professional degree programs, although most of the
      other occupations provide the opportunity to specialize after graduation. For the
      factors examined in this study, including entrance requirements, entrance
      examinations, program length, graduation requirements, and certification
      requirements, the Au.D. continues to be more similar to the nonprofessional
      degree models of psychology and speech-language pathology. The comparison with
      first professional degree programs yields information for possible further
      evolution of the education of audiologists.

PMID- 16796300
TI  - Effects of open-set and closed-set task demands on spoken word recognition.
AB  - Closed-set tests of spoken word recognition are frequently used in clinical
      settings to assess the speech discrimination skills of hearing-impaired
      listeners, particularly children. Speech scientists have reported robust effects
      of lexical competition and talker variability in open-set tasks but not closed
      set tasks, suggesting that closed-set tests of spoken word recognition may not be
      valid assessments of speech recognition skills. The goal of the current study was
      to explore some of the task demands that might account for this fundamental
      difference between open-set and closed-set tasks. In a series of four
      experiments, we manipulated the number and nature of the response alternatives.
      Results revealed that as more highly confusable foils were added to the response
      alternatives, lexical competition and talker variability effects emerged in
      closed-set tests of spoken word recognition. These results demonstrate a close
      coupling between task demands and lexical competition effects in lexical access
      and spoken word recognition processes.

PMID- 16796301
TI  - Evaluation of equivalency in two recordings of monosyllabic words.
AB  - Thirty "new" lists of monosyllabic words were created at the University of
      Melbourne and recorded by Australian and American English speakers. These new
      lists and the ten original CNC lists (Peterson and Lehiste, 1962) were used
      during the feasibility study of the Nucleus Research Platform 8 Cochlear Implant
      System (Holden et al, 2004). Performance was similar across original and new
      lists for six implanted Australian subjects; for four implanted U.S. subjects,
      mean performance was 23 percentage points lower with the new than with the
      original lists. To evaluate differences between original and new lists for the
      American English recording, 22 CI recipients were administered all 40 CNC lists
      (30 new and 10 original lists). The overall mean word score for the new lists was
      significantly lower (22.3 percentage points) than for the original lists.
      Acoustic analysis revealed that decreased performance was most likely due to
      reduced amplitudes of certain initial and final consonants. The new CNC lists can
      be used as more difficult test material for clinical research.

PMID- 16796302
TI  - The status of diagnostic testing following referral from universal newborn
      hearing screening.
AB  - The Joint Committee on Infant Hearing 2000 position statement includes guidelines
      for the development of Early Hearing Detection and Intervention programs. These
      guidelines provide specific recommendations for the audiologic test battery for
      infants who fail a newborn infant hearing screening. The recommended test battery
      includes electrophysiologic measures such as the ABR, frequency specific
      electrophysiologic tests, bone-conducted ABR, OAEs, tympanometry using high
      frequency probe stimuli, and acoustic reflexes. In the Commonwealth of Kentucky,
      42 centers are listed as providing follow-up diagnostic testing services for
      infants failing the newborn hearing screening. The purpose of this investigation
      was to determine how many of these centers were abiding by the Joint Committee
      guidelines. Results show that only three of 42 centers listed are providing
      services that meet the guidelines. Less than 50% of infants identified with
      hearing loss are referred for genetic evaluations by the audiologist. Only 19 of
      the 42 sites listed provide amplification services for infants identified with
      hearing loss.

PMID- 16796303
TI  - 3-Tesla clinical magnetic resonance imaging.

PMID- 16796304
TI  - Is 0.6T magnetic resonance mammography adequate in the detection of breast
      cancer?
AB  - PURPOSE: To evaluate whether relevant diagnostic information can be achieved when
      using magnetic resonance mammography (MRM) on mid-field as a supplement to
      conventional imaging and clinical examination in women with primary breast
      cancer. MATERIAL AND METHODS: 30 women (55 breasts containing 49 malignant
      tumors) planned for uni- or bilateral mastectomy were examined with dynamic MRM
      on mid-field, 0.6T. The women were examined with mammography (M) and
      ultrasonography (US) prior to MRM. The descriptions of the conventional
      examinations were evaluated retrospectively, whereas the MRM was evaluated
      prospectively, with knowledge of the M+US findings. Imaging findings suggesting
      malignancy were registered and correlated with pathology after mastectomy. A home
      made rating system for evaluation of the detected lesions was tested. RESULTS:
      MRM detected seven additional malignant tumors, failed to detect three lesions
      and characterized four as gray-zone lesions according to the rating system.
      Sensitivity of finding the tumors with M+US was 79.0%, with a PPV for malignant
      tumors of 84.4%. One breast in which MRM found a malignant tumor had not
      initially been examined with US. Sensitivity with MRM was 91.6%, with a positive
      predictive value of malignant tumors of 97.7%. CONCLUSION: MRM on mid-field seems
      to improve the detection of cancers when used as a supplement to M+US in women
      with primary breast cancer. We believe that the results are fair compared to MRM
      on high-field, although further research and refinement are needed.

PMID- 16796305
TI  - Learning curve for add-on stereotactic core needle breast biopsy.
AB  - PURPOSE: To evaluate the learning curve for an add-on 14 G stereotactic core
      needle biopsy (SCNB). MATERIAL AND METHODS: A total of 231 non-palpable breast
      lesions that had undergone add-on SCNB were evaluated in this prospective study.
      Five radiologists performed their first three biopsies under supervision.
      Subsequent, independently performed, biopsies were also evaluated. The samples
      were collected in three different containers: the first sample in container A,
      the second and third samples in container B, and subsequent samples in container
      C (available for four radiologists from the first biopsy on). Technically
      successful biopsies and false-negative rate in three container combinations (A,
      A+B, A+B+C) were reported as a function of operator experience. RESULTS:
      Technically unsuccessful biopsies occurred significantly more often in
      microcalcifications than in masses (14.9% versus 3.8%; P=0.04). For
      microcalcifications, the rate of successful biopsies was 75% (18/24) for the
      first 5 biopsies and 87.8% (79/90) for the subsequent biopsies (P=0.335); rates
      for the masses were 95.7% (22/23) and 96.3% (79/82) (P=1.0), respectively. A
      tendency was noted for the false-negative rate to be higher for the first five
      biopsies in three container combinations than in subsequent cases. CONCLUSION:
      Our results support the existence of a learning curve, especially in the biopsy
      of microcalcifications. More than three mentor-guided biopsies are needed.

PMID- 16796306
TI  - Computed-tomography-guided direct percutaneous transhepatic embolization of a
      bleeding hepatic artery branch aneurysm.
AB  - A case of successful direct percutaneous transhepatic coil embolization of a
      ruptured intrahepatic aneurysm under computed tomography (CT) guidance is
      presented. The patient had a history of multiple operations for liver
      echinococcosis and was transferred to the emergency department in a deteriorating
      clinical condition due to active hemorrhage. The aneurysm was treated with
      percutaneous transhepatic embolization under CT guidance. The procedure is not
      time-consuming and keeps the time interval between diagnosis and treatment to a
      minimum, thereby limiting subsequent blood loss.

PMID- 16796307
TI  - Popliteal vein aneurysm.
AB  - The incidence of a popliteal vein aneurysm is extremely low. Two cases of this
      rare venous anomaly are described. The epidemiology, morphology, and diagnostic
      methods are discussed and the potentially dangerous complications and treatment
      methods are presented.

PMID- 16796308
TI  - Value of repeat ultrasound-guided fine-needle aspiration in nodules with benign
      cytological diagnosis.
AB  - PURPOSE: To assess the value of repeat ultrasound-guided fine-needle aspiration
      (US-FNA) in nodules with benign cytological diagnosis. MATERIAL AND METHODS: One
      hundred-and-eighty-seven patients undergoing repeat US-FNA were included after a
      benign cytological diagnosis had been made by the initial US-FNA. They were
      divided into a re-aspiration group, who underwent repeat US-FNA within 6 months
      for a discordant pathological and clinico-radiological result, and a follow-up
      aspiration group, who underwent repeat US-FNA after 6 months without any clinical
      or radiological suspicion. The cancer rate in each group and the US findings of
      the later-diagnosed malignant nodules were assessed. RESULTS: Nine malignancies
      were verified in the 187 cases (4.8%) by repeat US-FNA or surgery. In 44 patients
      in the re-aspiration group, 6 malignancies were identified (13.6%), compared with
      3 malignancies in the 143 patients in the follow-up aspiration group (2.1%)
      (P<0.05). The later-diagnosed malignant nodules were an average of 1.0 cm in
      diameter; 66.7% were round; 66.7% were circumscribed; 100% were solid; 88.9% were
      hypoechoic; and 55.6% contained calcifications on US. CONCLUSION: The follow-up
      of nodules with benign cytological diagnosis without clinicoradiological
      suspicion of malignancy is warranted using imaging surveillance rather than
      repeated US-FNA.

PMID- 16796309
TI  - Impact of extended written information on patient anxiety and image motion
      artifacts during magnetic resonance imaging.
AB  - PURPOSE: To evaluate whether increased written information to patients prior to
      magnetic resonance imaging (MRI) decreases patient anxiety and image motion
      artifacts. MATERIAL AND METHODS: A two-group controlled experimental design was
      used. Of 242 patients, 118 received routinely given basic written information
      (control group) while 124 were given increased written information (intervention
      group). To measure patient anxiety before and during scanning, the self-report
      psychometric test State-Trait Anxiety Inventory (STAI) was used. After MR
      examination, the patients answered a questionnaire on satisfaction with the
      written information. The images were assessed with regard to motion artifacts.
      RESULTS: Motion artifacts were present in fewer patient images in the
      intervention group than in the control group (4.0% versus 15.4%,; P=0.003). There
      was no significant difference between the control and the intervention group
      regarding patient anxiety and satisfaction with the information. Women in both
      groups showed a higher level of anxiety than the men did. CONCLUSION: Increased
      information about the MRI scanning procedure and expected experiences during the
      scan may help patients to lie still during the sequences, with a decrease in
      motion artifacts. However, further research is needed to evaluate the effect of
      other interventions on patient anxiety during MRI scanning.

PMID- 16796310
TI  - New needle holder facilitates percutaneous fluoroscopy-guided sacroiliac
      puncture.
AB  - PURPOSE: To evaluate the success of a new guidance device for sacroiliac joint
      puncture. MATERIAL AND METHODS: The device was first tested on a human anatomical
      model and thereafter on two groups of patients. In the first group (n=8), the
      traditional hand-guided method was used, and in the second group (n=10) the
      needle-holder device. The parameters evaluated in each group were "the number of
      attempts", defined as the number of skin punctures, and "fluoroscopy-injection
      time", defined as the time from the beginning of the fluoroscopy to the end of
      the correct insertion of the needle into the joint. RESULTS: Sacroiliac injection
      with the new device required significantly fewer attempts (2.1 +/- 2 versus 4.3
      +/- 3) and shorter fluoroscopy injection times (8.9 +/- 3 min versus 15 +/- 5
      min; P<0.05). CONCLUSION: The new guidance device makes sacroiliac joint
      injection easier and prevents unnecessary exposure to radiation during the
      procedure.

PMID- 16796311
TI  - A short Larsen score is effective when evaluating radiographs in early rheumatoid
      arthritis.
AB  - PURPOSE: To compare the efficacy of the short Larsen score (LS 12) based on
      analysis of 12 areas with the original Larsen score (LS 40), which includes 40
      areas for assessing radiographic changes in rheumatoid arthritis. MATERIAL AND
      METHODS: The radiographs of the hands, wrists, and feet of 122 patients with
      early rheumatoid arthritis were evaluated by two radiologists using both the LS
      40 and LS 12 methods. Cross-sectional analysis of radiographs of 122 patients and
      longitudinal analysis in 68 patients were performed. RESULTS: There was no
      significant difference between the mean LS 40 and mean LS 12 in the cross
      sectional study. LS 12 correlated strongly (r=0.93, P<0.01) with LS 40 at the
      baseline, and the rate of progression was similar in both methods (r=0.89,
      P<0.01) in the longitudinal study. CONCLUSION: The short Larsen score was as
      efficient as the original method.

PMID- 16796312
TI  - 3D imaging of the whole spine at 3T compared to 1.5T: initial experiences.
AB  - PURPOSE: To describe our first experiences with a recently introduced 3T system
      for T2-weighted isotropic 3D whole-spine imaging. MATERIAL AND METHODS: Magnetic
      resonance imaging of the whole spine was performed by implementing an isotropic
      3D fast spin-echo sequence with variable flip-angle refocusing pulses at 3T and
      1.5T. Signal-to-noise ratio (SNR) was compared on both systems in eight subjects.
      RESULTS: Mean values for SNR were significantly higher at 3T (346+214) for 1.0 mm
      voxel size compared to 1.5T (202 +/- 41), but showed considerably higher
      variability at 3T. At 3T, measurements with 0.9 mm voxel size were possible with
      similar SNR as with 1.0 mm voxel size at 1.5T. CONCLUSION: High-resolution 3D
      imaging of the whole spine is feasible at 3T with an increased SNR compared to
      1.5T. Signal gain at 3T can be used to further increase spatial resolution.
      Pronounced interpatient variability of SNR at 3T may be a result of inhomogeneous
      RF deposition due to dielectric effects.

PMID- 16796313
TI  - Sphenoid sinus craniopharyngioma simulating mucocele.
AB  - We present a case of extracranial craniopharyngioma simulating a sphenoid sinus
      mucocele in a 12-year-old female who presented with progressive subacute left
      sided visual disturbance. Although infrasellar craniopharyngioma is a rare
      entity, the presence of foci of calcification within the lesion is a useful
      finding for diagnosis.

PMID- 16796314
TI  - Diffuse pneumocephalus associated with infratentorial and supratentorial
      hemorrhages as a complication of spinal surgery.
AB  - A 23-year-old woman was transferred to our department with loss of consciousness
      6 h after undergoing rod placement for thoracolumbar scoliosis. Both computed
      tomography and magnetic resonance imaging of the brain revealed diffuse
      pneumocephalus and infra- and supratentorial hemorrhages. The pedicular screw
      tracts were analyzed with computed tomography and misplacement of a screw was
      noticed. It was thought that inadvertent dural injury had occurred at the time of
      insertion. The patient was re-operated and the dural tear was repaired. To our
      knowledge, this is the first description of these uncommon complications in one
      patient after spine surgery.

PMID- 16796315
TI  - Clinical 1H magnetic resonance spectroscopy of brain metastases at 1.5T and 3T.
AB  - PURPOSE: To investigate whether improvements in signal-to-noise ratio (SNR) and
      spectral resolution are found in spectra from patients with brain metastases
      obtained at higher magnetic field strengths using standard clinical
      instrumentation. MATERIAL AND METHODS: Six patients with brain metastases, 13
      healthy volunteers, and a phantom containing brain metabolites were examined
      using two clinical MR instruments operating at 1.5T (Siemens) and 3T (Philips)
      with standard clinical head coils. Spectra were obtained using a point resolved
      spectroscopy pulse sequence, echo times (TE) 32 ms and 144 ms, and repetition
      time 2000 ms from a volume-of-interest (VOI) of size 15 x 15 x 15 mm3. SNR and
      spectral resolution of the metabolites N-acetylaspartate, choline, and creatine
      compounds in spectra from 3T were compared to the 1.5T spectra. RESULTS: In
      general, spectral resolution was improved by 25-30% at higher magnetic field
      strength. Only minor improvements in SNR were obtained at 3T using short echo
      time and 20-50% at long echo time. CONCLUSION: SNR and spectral resolution were
      improved at higher magnetic field strength, especially with TE 144 ms, including
      spectra from patients with heterogeneous brain tumors. However, differences in
      the defined effective VOI, particularly at short echo time, reduced the expected
      effect of increased magnetic field strength on the measured SNR.

PMID- 16796316
TI  - Magnetic resonance imaging and diffusion tensor analysis of lymphomatoid
      granulomatosis of the brain.
AB  - We present the case of a 56-year-old man suffering from acquired immune
      deficiency syndrome associated with lymphomatoid granulomatosis. Magnetic
      resonance imaging performed because of convulsions revealed an ill-defined
      frontal mass showing hypointense on T1WI and slightly hypointense on T2WI with
      surrounding edema. An elevated uptake was found on T1-201 single photo emission
      computed tomography consistent with a central nervous system lymphoma. However,
      the apparent diffusion coefficient ratio calculated from diffusion-tensor
      acquisitions was 1.53 and was higher than that of lymphomas in previous reports.
      Stereotactic brain biopsy was performed and lymphomatoid granulomatosis was
      confirmed.

PMID- 16796317
TI  - Primary leiomyosarcoma of the oral tongue: magnetic resonance and ultrasonography
      findings with histopathologic correlation.
AB  - Leiomyosarcoma is a malignant smooth muscle tumor that frequently occurs in the
      gastrointestinal tract and female genital tract. It is aggressive and tends to
      recur and metastasize. Clinical behavior is unpredictable, mostly influenced by a
      proper surgical approach. Oral leiomyosarcoma, in particular of the tongue, is
      extremely rare and poorly documented in the radiology literature. Diagnostic
      assessment of oral leiomyosarcoma is often challenging, mostly founded on its
      peculiar immunohistological features. However, imaging evaluation is essential in
      staging and for preoperative planning. We illustrate the case of a 52-year-old
      woman with 2-months history of a painless growing mass on the left hemitongue,
      with magnetic resonance and ultrasonographic features correlated to
      histopathologic examination.

PMID- 16796318
TI  - Metacarpophalangeal pattern profile analysis: useful diagnostic tool for
      differentiating between dyschondrosteosis, Turner syndrome, and
      hypochondroplasia.
AB  - PURPOSE: To assess the value of the metacarpophalangeal pattern profile (MCPP)
      analysis as a diagnostic tool for differentiating between patients with
      dyschondrosteosis, Turner syndrome, and hypochondroplasia. MATERIAL AND METHODS:
      Radiographic and clinical data from 135 patients between 1 and 51 years of age
      were collected and analyzed. The study included 25 patients with
      hypochondroplasia (HCP), 39 with dyschondrosteosis (LWD), and 71 with Turner
      syndrome (TS). Hand pattern profiles were calculated and compared with those of
      110 normal individuals. Pearson correlation coefficient (r) and multivariate
      discriminant analysis were used for pattern profile analysis. Pattern variability
      index, a measure of dysmorphogenesis, was calculated for LWD, TS, HCP, and normal
      controls. RESULTS: Our results demonstrate that patients with LWD, TS, or HCP
      have distinct pattern profiles that are significantly different from each other
      and from those of normal controls. Discriminant analysis yielded correct
      classification of normal versus abnormal individuals in 84% of cases.
      Classification of the patients into LWD, TS, and HCP groups was successful in
      75%. The correct classification rate was higher (85%) when differentiating two
      pathological groups at a time. Pattern variability index was not helpful for
      differential diagnosis of LWD, TS, and HCP. CONCLUSION: Patients with LWD, TS, or
      HCP have distinct MCPPs and can be successfully differentiated from each other
      using advanced MCPP analysis. Discriminant analysis is to be preferred over
      Pearson correlation coefficient because it is a more sensitive and specific
      technique. MCPP analysis is a helpful tool for differentiating between syndromes
      with similar clinical and radiological abnormalities.

PMID- 16796319
TI  - Segmental dilatation of the ileum: A report of two cases.
AB  - Segmental dilatation of the ileum is one of the uncommon causes of intestinal
      obstruction. Preoperative diagnosis of segmental dilatation of the ileum is
      difficult. We report two cases of this condition that were diagnosed
      preoperatively by contrast studies.

PMID- 16796320
TI  - Ectopic pregnancy--the leash sign. A new sign on transvaginal Doppler ultrasound.
AB  - PURPOSE: To evaluate the efficacy of transvaginal Doppler ultrasound in the
      diagnosis of ectopic pregnancy. MATERIAL AND METHODS: Over a period of 3 years,
      100 women with signs suggestive of a possible ectopic pregnancy were evaluated
      with endovaginal sonography and Doppler. The fallopian tubes were examined for
      the presence of low-resistance arterial flow. RESULTS: Of the 100 cases, 19 women
      had ectopic pregnancies. It was observed that all cases of ectopic pregnancies
      had a typical eccentric leash of vessels on color Doppler that showed a low
      resistance placental type of flow on spectral Doppler. CONCLUSION: We propose a
      new reliable sign of ectopic pregnancy called the leash sign. This sign has a
      sensitivity of 100% and specificity of 99%, a positive predictive value of 95%
      and negative predictive value of 100%, thus helping in the diagnosis of early
      ectopic pregnancy, and resulting in earlier treatment with reduced morbidity and
      mortality.

PMID- 16796321
TI  - Sales reps in the OR? Get ready to turn wisdom on its head.

PMID- 16796322
TI  - Flexing your muscle: How to increase your value and influence.

PMID- 16796323
TI  - Determining capital dollars based on technology obsolescence.

PMID- 16796324
TI  - Translating the concepts behind gateways.
AB  - The intention of this installment of IT World is to bring the various aspects of
      gateways into view. You can see how loosely the gateway term is used and how the
      meaning of the term has changed over time. Keep concepts of gateways in order by
      considering their main function. The main function for gateways is to convert
      from one set of communication protocols to some other set of communication
      protocols-thus allowing access to otherwise incompatible networks. These
      functions include: Protocol Conversion--When a message is prepared for
      transmission, each layer adds control information unique to the protocol used at
      that layer (see Figure 1). The gateway must be able to convert control
      information to the format the receiving network expects. Services affected may
      include message segmentation and reassembly, data flow control, and error
      detection and recovery. Protocol converters connect networks that use different
      communication protocols. Address Translation--Different networks may employ
      different network addressing schemes, mechanisms, and network address structures.
      The gateway must be able to interpret network addresses in one network and
      convert them into appropriate network addresses for the other network while
      holding the validity of the address resolution. Examples that include both
      protocol conversion and address translation are when a gateway converts a TCP/IP
      packet to a NetWare IPX packet and vice versa or from AppleTalk to DECnet, and so
      on. Message Format Conversion--Different networks can employ different message
      formats, maximum message sizes, or character codes. The gateway must be able to
      convert messages to an appropriate format, size, and coding for the receiving
      network. Examples are CGI and an email gateway (which is a layer 7-application
      layer-gateway). Keep these main concepts in mind while surfing the web trying to
      find out more information about what your gateways are up to!

PMID- 16796325
TI  - Creating a systems approach to patient safety through better teamwork.
AB  - Using a systems engineering approach for the delivery of safe, reliable,
      consistently high quality healthcare is possible, based on the successes in other
      industries. To realize the level of reengineering required in healthcare, teams
      must function across disciplines and departments as a unified organization. By
      creating and maintaining HRTs, existing hierarchies will flatten and HROs will
      become part of the healthcare delivery system. The organization must support
      these teams with the proper tools, technology, and culture in order for the HRTs
      to complete their patient care missions successfully, consistently, efficiently,
      and most of all, safely. Government/compliance agencies must partner with
      organizations for the systems engineering approach to succeed in healthcare, so
      that policy ultimately originates from the consumer/patient through the care team
      and the organization, as opposed to a top-down mandate.

PMID- 16796326
TI  - Maximize your experience...make job fairs work for you.

PMID- 16796327
TI  - Case study: Computer telephony and online surveys improve service quality.

PMID- 16796328
TI  - Infant incubators.

PMID- 16796329
TI  - Three steps to an equipment planning process that works.

PMID- 16796330
TI  - Management responsibility enables success.

PMID- 16796331
TI  - Risk-based approach to device management has multiple pathways.

PMID- 16796332
TI  - Continuing education strengthens staff abilities.

PMID- 16796333
TI  - A primer on picture archival and communication systems.

PMID- 16796334
TI  - Are your CO2 lasers precise?

PMID- 16796335
TI  - Medical equipment management strategies.
AB  - Clinical engineering professionals need to continually review and improve their
      management strategies in order to keep up with improvements in equipment
      technology, as well as with increasing expectations of health care organizations.
      In the last 20 years, management strategies have evolved from the initial
      obsession with electrical safety to flexible criteria that fit the individual
      institution's needs. Few hospitals, however, are taking full advantage of the
      paradigm shift offered by the evolution of joint Commission standards. The focus
      should be on risks caused by equipment failure, rather than on equipment with
      highest maintenance demands. Furthermore, it is not enough to consider risks
      posed by individual pieces of equipment to individual patients. It is critical to
      anticipate the impact of an equipment failure on larger groups of patients,
      especially when dealing with one of a kind, sophisticated pieces of equipment
      that are required to provide timely and accurate diagnoses for immediate
      therapeutic decisions or surgical interventions. A strategy for incorporating
      multiple criteria to formulate appropriate management strategies is provided in
      this article.

PMID- 16796336
TI  - Developments in ambulatory electrocardiography.
AB  - Cardiovascular disease (CVD) is the leading cause of death in many developed
      countries. There is a need for cardiovascular monitoring devices that can
      supplement traditional medical and clinical care by enabling the diagnosis of
      conditions with infrequent symptoms, the timely detection of critical signs that
      are precursors to sudden cardiac death, and the long-term management of chronic
      conditions through monitoring of symptoms, risk factors, and the effects of
      therapy. This paper provides an overview of ambulatory electrocardiogram (ECG)
      monitors, which are one of the most widely prescribed diagnostic procedures for
      cardiovascular disease. The engineering challenges associated with ambulatory
      electrocardiography are discussed, and technological improvement areas that are
      the focus of current research effort are reviewed.

PMID- 16796337
TI  - ANSI/AAMI ES60601-1: A new approach to device standards.

PMID- 16796338
TI  - Wireless technology: communications and challenges in healthcare.

PMID- 16796339
TI  - Opposition to public water fluoridation.

PMID- 16796340
TI  - Economics and benefits of flouride treated community water supplies.

PMID- 16796341
TI  - The importance of probiotic supplementation in conjunction with orthodontic
      therapy.

PMID- 16796342
TI  - Handling broken appointments, low case acceptance, and high stress through
      patient education.

PMID- 16796343
TI  - Oral pathology quiz #51. Case number 1. Squamous cell carcinoma.

PMID- 16796344
TI  - Oral pathology quiz #51. Case number 3. Cementoblastoma.

PMID- 16796345
TI  - Is your advertising a liability risk?

PMID- 16796346
TI  - Processing of dental instruments--Are you following the correct procedures to
      ensure that your instruments are safe for patient treatment?

PMID- 16796347
TI  - Risk management matters, property loss aid agreement: continue practicing while
      your office is under construction.

PMID- 16796348
TI  - Medical quick reference glossary for dental clinicians: diabetes.

PMID- 16796349
TI  - Monitoring tablet surface roughness during the film coating process.
AB  - The purpose of this study was to evaluate the change of surface roughness and the
      development of the film during the film coating process using laser profilometer
      roughness measurements, SEM imaging, and energy dispersive X-ray (EDX) analysis.
      Surface roughness and texture changes developing during the process of film
      coating tablets were studied by noncontact laser profilometry and scanning
      electron microscopy (SEM). An EDX analysis was used to monitor the magnesium
      stearate and titanium dioxide of the tablets. The tablet cores were film coated
      with aqueous hydroxypropyl methylcellulose, and the film coating was performed
      using an instrumented pilot-scale side-vented drum coater. The SEM images of the
      film-coated tablets showed that within the first 30 minutes, the surface of the
      tablet cores was completely covered with a thin film. The magnesium signal that
      was monitored by SEM-EDX disappeared after ~15 to 30 minutes, indicating that the
      tablet surface was homogeneously covered with film coating. The surface roughness
      started to increase from the beginning of the coating process, and the increase
      in the roughness broke off after 30 minutes of spraying. The results clearly
      showed that the surface roughness of the tablets increased until the film coating
      covered the whole surface area of the tablets, corresponding to a coating time
      period of 15 to 30 minutes (from the beginning of the spraying phase).
      Thereafter, the film only became thicker. The methods used in this study were
      applicable in the visualization of the changes caused by the film coating on the
      tablet surfaces.

PMID- 16796350
TI  - A tumor vasculature targeted liposome delivery system for combretastatin A4:
      design, characterization, and in vitro evaluation.
AB  - The objective of this study was to develop an efficient tumor vasculature
      targeted liposome delivery system for combretastatin A4, a novel antivascular
      agent. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC),
      cholesterol, distearoyl phosphoethanolamine-polyethylene-glycol-2000 conjugate
      (DSPE-PEG), and DSPE-PEG-maleimide were prepared by the lipid film hydration and
      extrusion process. Cyclic RGD (Arg-Gly-Asp) peptides with affinity for
      alphavbeta3-integrins expressed on tumor vascular endothelial cells were coupled
      to the distal end of PEG on the liposomes sterically stabilized with PEG (long
      circulating liposomes, LCL). The liposome delivery system was characterized in
      terms of size, lamellarity, ligand density, drug loading, and leakage properties.
      Targeting nature of the delivery system was evaluated in vitro using cultured
      human umbilical vein endothelial cells (HUVEC). Electron microscopic observations
      of the formulations revealed presence of small unilamellar liposomes of
      approximately 120 nm in diameter. High performance liquid chromatography
      determination of ligand coupling to the liposome surface indicated that more than
      99% of the RGD peptides were reacted with maleimide groups on the liposome
      surface. Up to 3 mg/mL of stable liposomal combretastatin A4 loading was achieved
      with approximately 80% of this being entrapped within the liposomes. In the in
      vitro cell culture studies, targeted liposomes showed significantly higher
      binding to their target cells than nontargeted liposomes, presumably through
      specific interaction of the RGD with its receptors on the cell surface. It was
      concluded that the targeting properties of the prepared delivery system would
      potentially improve the therapeutic benefits of combretastatin A4 compared with
      nontargeted liposomes or solution dosage forms.

PMID- 16796351
TI  - Role of surfactant and pH on dissolution properties of fenofibrate and glipizide-
      a technical note.

PMID- 16796352
TI  - Optimization of bilayer floating tablet containing metoprolol tartrate as a model
      drug for gastric retention.
AB  - The purpose of the present study was to develop an optimized gastric floating
      drug delivery system (GFDDS) containing metoprolol tartrate (MT) as a model drug
      by the optimization technique. A 2(3) factorial design was employed in
      formulating the GFDDS with total polymer content-to-drug ratio (X1), polymer-to
      polymer ratio (X2), and different viscosity grades of hydroxypropyl methyl
      cellulose (HPMC) (X3) as independent variables. Four dependent variables were
      considered: percentage of MT release at 8 hours, T50%, diffusion coefficient, and
      floating time. The main effect and interaction terms were quantitatively
      evaluated using a mathematical model. The results indicate that X1 and X2
      significantly affected the floating time and release properties, but the effect
      of different viscosity grades of HPMC (K4M and K10M) was nonsignificant.
      Regression analysis and numerical optimization were performed to identify the
      best formulation. Fickian release transport was confirmed as the release
      mechanism from the optimized formulation. The predicted values agreed well with
      the experimental values, and the results demonstrate the feasibility of the model
      in the development of GFDDS.

PMID- 16796354
TI  - Characterization of DNA degradation using direct current conductivity and dynamic
      dielectric relaxation techniques.
AB  - The purpose of this study was to evaluate DNA degradation upon thermal heating
      using dielectric relaxation and direct current (DC) conductivity methods. Herring
      sperm DNA, human growth hormone (HgH) plasmid DNA, and secreted alkaline
      phosphatase (SEAP) plasmid DNA were used as the examples. DNA was heated at 80
      degrees C for 1 hour. The dielectric relaxation spectra as a function of the
      applied field frequency were measured for HgH DNA at 0.5 hours and at 1 hour. The
      frequency range covered was from 10 kHz to 100 kHz. The DC conductivity
      measurements were made for all 3 kinds of DNA at 4 time points: 0 hours, 0.5
      hours, 0.75 hours, and 1 hour. At each time point the DC conductivity was
      measured for each sample as a function of concentration via water dilution. The
      results show that the dielectric relaxation method is less sensitive in
      characterizing heat-driven DNA degradation. Conversely, DC conductivity is very
      sensitive. The semiquantitative dependence of the conductivity upon heating
      suggests that DNA degradation involves more than plasmid DNA nicking. Double
      strand and single strand breaks may also occur. In addition, herring sperm DNA,
      HgH DNA, and SEAP DNA, though similar in their DC conductivity functional forms
      upon dilution, exhibit significant differences in their responses to sustained
      heating.

PMID- 16796353
TI  - Applying pattern recognition methods to analyze the molecular properties of a
      homologous series of nitrogen mustard agents.
AB  - The purpose of this research was to analyze the pharmacological properties of a
      homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1
      to 9 methylene groups (-CH2-) between 2 -N(CH2CH2Cl)2 groups. These compounds
      were shown to have significant correlations and associations in their properties
      after analysis by pattern recognition methods including hierarchical
      classification, cluster analysis, nonmetric multi-dimensional scaling (MDS),
      detrended correspondence analysis, K-means cluster analysis, discriminant
      analysis, and self-organizing tree algorithm (SOTA) analysis. Detrended
      correspondence analysis showed a linear-like association of the 9 homologs, and
      hierarchical classification showed that each homolog had great similarity to at
      least one other member of the series-as did cluster analysis using paired-group
      distance measure. Nonmetric multi-dimensional scaling was able to discriminate
      homologs 2 and 3 (by number of methylene groups) from homologs 4, 5, and 6 as a
      group, and from homologs 7, 8, and 9 as a group. Discriminant analysis, K-means
      cluster analysis, and hierarchical classification distinguished the high
      molecular weight homologs from low molecular weight homologs. As the number of
      methylene groups increased the aqueous solubility decreased, dermal permeation
      coefficient increased, Log P increased, molar volume increased, parachor
      increased, and index of refraction decreased. Application of pattern recognition
      methods discerned useful interrelationships within the homologous series that
      will determine specific and beneficial clinical applications for each homolog and
      methods of administration.

PMID- 16796355
TI  - Comparative study of the fluid dynamics of bottom spray fluid bed coaters.
AB  - Fluid dynamics of pellets processed in bottom spray traditional Wurster coating
      and swirl accelerated air (precision) coating were compared with the intent to
      understand and facilitate improvements in the coating processes. Fluid dynamics
      was described by pellet mass flow rate (MFR) obtained using a pellet collection
      system and images captured using high speed photography. Pellet flow within the
      partition column was found to be denser and slower in Wurster coating than in
      precision coating, suggesting a higher tendency of agglomeration during the
      coating process. The influence of partition gap and load on the MFR indicated
      that the mechanism of transport of pellets into the coating zone in precision
      coating depended on a strong suction, whereas in Wurster coating, pellets were
      transported by a combination of peripheral fluidization, gravity, and weak
      suction pressure. In precision coating, MFR was found to increase uniformly with
      air flow rate and atomizing pressure, whereas MFR in Wurster coating did not
      correlate as well with air flow rate and atomizing pressure. This demonstration
      showed that transport in precision coating was air dominated. In conclusion,
      fluid dynamics in precision coating was found to be air dominated and dependent
      on pressure differential, thus it is more responsive to changes in operational
      variables than Wurster coating.

PMID- 16796356
TI  - Mucoadhesive, thermosensitive, prolonged-release vaginal gel for
      clotrimazole:beta-cyclodextrin complex.
AB  - The purpose of this study was to achieve a better therapeutic efficacy and
      patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been
      formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%)
      together with mucoadhesive polymers such as Carbopol 934 and
      hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility,
      clotrimazole was incorporated as its inclusion complex with 1:1 molar ratio with
      beta-cyclodextrin. The inclusion complex was thoroughly characterized using
      various techniques, including 1H NMR spectroscopy, FT IR spectrophotometry,
      differential scanning calorimetry, scanning electron microscopy, phase solubility
      studies, and determination of stability constant (k(1:1)). The gelation
      temperature and rheological behavior of different formulations at varying
      temperatures were measured. In vitro release profiles of the gels were determined
      in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin
      slowed down the release of clotrimazole considerably. Carbopol 934, on the other
      hand, was found to interact with beta-cyclodextrin, inducing precipitation. As
      far as rheological properties are concerned, thermosensitive in situ gelling was
      obtained with formulations containing drug:cyclodextrin complex rather than with
      free drug. Thus, the optimum formulation for a controlled-release thermosensitive
      and mucoadhesive vaginal gel was determined to be clotrimazole:beta-cyclodextrin
      1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing
      continuous and prolonged release of active material above MIC values.

PMID- 16796357
TI  - Heat and mass transfer scale-up issues during freeze-drying, III: control and
      characterization of dryer differences via operational qualification tests.
AB  - The objective of this research was to estimate differences in heat and mass
      transfer between freeze dryers due to inherent design characteristics using data
      obtained from sublimation tests. This study also aimed to provide guidelines for
      convenient scale-up of the freeze-drying process. Data obtained from sublimation
      tests performed on laboratory-scale, pilot, and production freeze dryers were
      used to evaluate various heat and mass transfer parameters: nonuniformity in
      shelf surface temperatures, resistance of pipe, refrigeration system, and
      condenser. Emissivity measurements of relevant surfaces such as the chamber wall
      and the freeze dryer door were taken to evaluate the impact of atypical radiation
      heat transfer during scale-up. "Hot" and "cold" spots were identified on the
      shelf surface of different freeze dryers, and the impact of variation in shelf
      surface temperatures on the primary drying time and the product temperature
      during primary drying was studied. Calculations performed using emissivity
      measurements on different freeze dryers suggest that a front vial in the
      laboratory lyophilizer received 1.8 times more heat than a front vial in a
      manufacturing freeze dryer operating at a shelf temperature of -25 degrees C and
      a chamber pressure of 150 mTorr during primary drying. Therefore, front vials in
      the laboratory are much more atypical than front vials in manufacturing. Steady
      state heat and mass transfer equations were used to study a combination of
      different scale-up issues pertinent during lyophilization cycles commonly used
      for the freeze-drying of pharmaceuticals.

PMID- 16796358
TI  - Fast-disintegrating sublingual tablets: effect of epinephrine load on tablet
      characteristics.
AB  - The aim of this study was to evaluate the effect of increasing epinephrine load
      on the characteristics of fast-disintegrating sublingual tablets for the
      potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C,
      and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively,
      and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9:1),
      were prepared by direct compression, at a range of compression forces. Tablet
      weight variation, content uniformity, hardness, disintegration time, wetting
      time, and friability were measured for each formulation at each compression
      force. All 4 tablet formulations at each compression force were within the United
      States Pharmacopeia (USP) limits for weight variation and content uniformity. A
      linear increase in compression force resulted in an exponential increase in
      hardness for all formulations, a linear increase in disintegration and wetting
      times of A, and an exponential increase in disintegration and wetting times of B,
      C, and D. At a mean +/- SD hardness of > or = 2.3 +/- 0.2 kg, all tablet
      formulations passed the USP friability test. At a mean +/- SD hardness of < or =
      3.1 +/- 0.2 kg, all tablet formulations resulted in disintegration and wetting
      times of <10 seconds and <30 seconds, respectively. Tablets with drug loads from
      0% to 24% epinephrine can be formulated with hardness, disintegration times, and
      wetting times suitable for sublingual administration.

PMID- 16796359
TI  - Mathematical modeling of an aqueous film coating process in a Bohle Lab-Coater,
      part 1: development of the model.
AB  - The purpose of this study was to develop a model to predict (1) air and product
      temperatures, (2) product moisture, and (3) air humidity during an aqueous
      coating process using a Bohle Lab-Coater. Because of the geometrical properties
      and the airflow, the drum of the Bohle Lab-Coater can in principle be divided
      into 2 zones of equal size-the drying and the spraying zones. For each zone, 4
      balance equations could be set up describing the change of the air humidity, the
      product moisture, the enthalpy of the air, and the enthalpy of the product in
      each zone. For this purpose, knowledge regarding heat and mass transfer and also
      the motion of the tablets in drums was used. Based on the considerations of the
      heat and mass transfer, a set of first-order coupled ordinary differential
      equations (ODEs) was developed. This set of ODEs can be solved numerically. In
      this part, the development of the model is described in detail, whereas the
      application of the model can be found in part 2.

PMID- 16796360
TI  - Mathematical modeling of an aqueous film coating process in a Bohle Lab-Coater:
      part 2: application of the model.
AB  - For the prediction of the air and product temperatures, the product moisture, and
      the air humidity during a coating process in a Bohle Lab-Coater, a model was
      developed. The purpose of this work was to determine the limit moisture, the
      critical moisture, and the constant for the exchange rate between both zones and
      to use these values for other sets of experiments to test the model. The
      adaptation of the 3 parameters (limit moisture, critical moisture, and exchange
      rate constant) was done by calculation of the product temperature in both zones
      for several sets of parameters in order to minimize the sum of square deviation
      between the calculated and the measured product temperatures. This set of
      parameters was used to test the validity of the model. By applying the model, the
      product temperature could be predicted based on the product, process, and
      equipment-related parameters. Hence, the model can be used to theoretically
      investigate the influence of different process parameters. The mean difference
      between the predicted and measured product temperatures in the steady state is
      approximately 2 up to 3 K using the determined parameter set for the limit
      moisture, the critical moisture, and the exchange rate constant. The model is
      useful for the prediction of the air and product temperatures, the product
      moisture, and air humidity during a coating process in the Bohle Lab-Coater using
      round, biconvex tablets.

PMID- 16796361
TI  - Viscoelastic properties of a virucidal cream containing the monoglyceride
      monocaprin: effects of formulation variables: a technical note.

PMID- 16796362
TI  - Characterization of microemulsion structures in the pseudoternary phase diagram
      of isopropyl palmitate/water/Brij 97:1-butanol.
AB  - This research was aimed to characterize microemulsion systems of isopropyl
      palmitate (IPP), water, and 2:1 Brij 97 and 1-butanol by different experimental
      techniques. A pseudoternary phase diagram was constructed using water titration
      method. At 45% wt/wt surfactant system, microemulsions containing various ratios
      of water and IPP were prepared and identified by electrical conductivity,
      viscosity, differential scanning calorimetry (DSC), cryo-field emission scanning
      electron microscopy (cryo-FESEM) and nuclear magnetic resonance (NMR). The
      results from conductivity and viscosity suggested a percolation transition from
      water-in-oil (water/oil) to oil-in-water (oil/water) microemulsions at 30% wt/wt
      water. From DSC results, the exothermic peak of water and the endothermic peak of
      IPP indicated that the transition of water/oil to oil/water microemulsions
      occurred at 30% wt/wt water. Cryo-FESEM photomicrographs revealed globular
      structures of microemulsions at higher than 15% wt/wt water. In addition, self
      diffusion coefficients determined by NMR reflected that the diffusability of
      water increased at higher than 35% wt/wt water, while that of IPP was in reverse.
      Therefore, the results from all techniques are in good agreement and indicate
      that the water/oil and oil/water transition point occurred in the range of 30% to
      35% wt/wt water.

PMID- 16796363
TI  - Preparation and in vitro evaluation of polystyrene-coated diltiazem-resin complex
      by oil-in-water emulsion solvent evaporation method.
AB  - The purpose of this study was to examine the suitability of polystyrene-coated
      (PS-coated) microcapsules of drug-resin complex for achieving prolonged release
      of diltiazem-HCl, a highly water-soluble drug, in simulated gastric and
      intestinal fluid. The drug was bound to Indion 254, a cation-exchange resin, and
      the resulting resinate was microencapsulated with PS using an oil-in-water
      emulsion-solvent evaporation method. The effect of various formulation parameters
      on the characteristics of the microcapsules was studied. Mean diameter and
      encapsulation efficiency of the microcapsules rose with an increase in the
      concentration of emulsion stabilizer and the coat/core ratio, while the same
      characteristics tended to decrease with an increase in the volume of the organic
      disperse phase. The desorption of drug from the uncoated resinate was quite rapid
      and independent of the pH of the dissolution media. On the other hand, the drug
      release from the microcapsules was prolonged for different periods of time
      depending on the formulation parameters and was also found to be independent of
      the pH of the dissolution media. Both the encapsulation efficiency and the
      retardation of drug release were found to be dependent on the uniformity of
      coating, which in turn was influenced by the formulation parameters. Kinetic
      studies revealed that the desorption of drug from the resinate obeyed the typical
      particle diffusion process, whereas the drug release from the microencapsulated
      resinate followed the diffusion-controlled model in accordance with the Higuchi
      equation. PS appeared to be a suitable polymer to provide prolonged release of
      diltiazem independent of the pH of the dissolution media.

PMID- 16796364
TI  - Characterization of 5-fluorouracil microspheres for colonic delivery.
AB  - The purpose of this investigation was to prepare and evaluate the colon-specific
      microspheres of 5-fluorouracil for the treatment of colon cancer. Core
      microspheres of alginate were prepared by the modified emulsification method in
      liquid paraffin and by cross-linking with calcium chloride. The core microspheres
      were coated with Eudragit S-100 by the solvent evaporation technique to prevent
      drug release in the stomach and small intestine. The microspheres were
      characterized by shape, size, surface morphology, size distribution,
      incorporation efficiency, and in vitro drug release studies. The outer surfaces
      of the core and coated microspheres, which were spherical in shape, were rough
      and smooth, respectively. The size of the core microspheres ranged from 22 to 55
      microm, and the size of the coated microspheres ranged from 103 to 185 microm.
      The core microspheres sustained the drug release for 10 hours. The release
      studies of coated microspheres were performed in a pH progression medium
      mimicking the conditions of the gastrointestinal tract. Release was sustained for
      up to 20 hours in formulations with core microspheres to a Eudragit S-100 coat
      ratio of 1:7, and there were no changes in the size, shape, drug content,
      differential scanning calorimetry thermogram, and in vitro drug release after
      storage at 40 degrees C/75% relative humidity for 6 months.

PMID- 16796365
TI  - Spherical agglomeration of mefenamic acid and nabumetone to improve micromeritics
      and solubility: a technical note.

PMID- 16796366
TI  - Commercial reference shape standards use in the study of particle shape effect on
      laser diffraction particle size analysis.
AB  - The purpose of this paper is to describe the use of LGC Promochem AEA 1001 to AEA
      1003 monosized fiber-analog shape standards in the study of the effect of
      particle shape on laser diffraction (LD) particle size analysis (psa). The psa of
      the AEA standards was conducted using LD psa systems from Beckman Coulter,
      Horiba, and Malvern Instruments. Flow speed settings, sample refractive index
      values, and sample cell types were varied to examine the extent to which the
      shape effect on LD psa results is modified by these variables. The volume and
      number probability plots resulting from these measurements were each
      characterized by a spread in the particle size distribution that roughly extended
      from the breadth to the longest dimension of the particles. For most of the
      selected sample refractive index values, the volume probability plots were
      characterized by apparent bimodal distributions. The results, therefore, provide
      experimental verification of the conclusions from theoretical studies of LD psa
      system response to monosized elliptical particles in which this apparent
      bimodality was the predicted result in the case of flow-oriented particles. The
      data support the findings from previous studies conducted over the past 10 years
      that have called into question the verity of the tenets of, and therefore the
      value of the application of, the equivalent spherical volume diameter theory and
      the random particle orientation model to the interpretation of LD psa results
      from measurements made on nonspherical particles.

PMID- 16796367
TI  - Studies on effect of pH on cross-linking of chitosan with sodium
      tripolyphosphate: a technical note.

PMID- 16796368
TI  - The effect of selected antioxidants on the kinetics of changes in the stability
      of an HTK solution: a technical note.

PMID- 16796369
TI  - Dissolution improvement of high drug-loaded solid dispersion.
AB  - This study focused on an investigation of a high drug-loaded solid dispersion
      system consisting of drug, carrier, and surfactant. Solid dispersions of a water
      insoluble ofloxacin (OFX) with polyethylene glycol (PEG) of different molecular
      weights, namely binary solid dispersion systems, were prepared at drug to carrier
      not less than 5:5. Polysorbate 80, a nonionic surfactant, was incorporated into
      the binary solid dispersion systems as the third component to obtain the ternary
      solid dispersion systems. The powder x-ray diffraction and differential scanning
      calorimetric studies indicated that crystalline OFX existed in the solid
      dispersions with high drug loading. However, a decreased crystallinity of the
      solid dispersions obtained revealed that a portion of OFX was in an amorphous
      state. The results indicated a remarkably improved dissolution of drug from the
      ternary solid dispersion systems when compared with the binary solid dispersion
      systems. This was because of polysorbate 80, which improved wettability and
      solubilized the non-molecularly dispersed or crystalline fraction of OFX.

PMID- 16796370
TI  - A mucoadhesive in situ gel delivery system for paclitaxel.
AB  - MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in
      human breast cancer and colon cancer. The objective of this study was to develop
      an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for
      sustained and targeted delivery of anticancer drugs. The delivery system
      consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid
      containing PTX. The in vitro release of PTX from the gel was performed in
      presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54%
      (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin
      producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies.
      Transport of PTX from solution and gel delivery system was performed in side by
      side diffusion chambers from apical to basal (A-B) and basal to apical (B-A)
      directions. In vitro release studies revealed that within 4 hours, only 7.61% +/-
      0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%,
      and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80.
      However, in presence of surfactant (0.05% wt/vol) in the dissolution medium,
      percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/-
      1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell
      monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The
      highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX
      transport from gels as compared with Caco-2 cells. Transport of PTX from
      mucoadhesive gels was shown to be influenced by the mucin-producing capability of
      cell.

PMID- 16796371
TI  - Fluid bed drying of guarana (Paullinia cupana HBK) extract: effect of process
      factors on caffeine content.
AB  - The aim of this study was to study the convective drying of the hydroalcoholic
      extracts obtained from powdered guarana seeds in a spouted bed dryer. The
      influence of process variables, such as the convective airflow rate, extract feed
      rate, and air inlet temperature, on the quality of the dry extract was determined
      using the caffeine and moisture content for the process evaluation. The caffeine
      content in the alcoholic and dried extracts was determined by capillary gas
      chromatography. The experiments were performed following a 3(3) factorial design
      and the data analyzed by response surface. The analysis of dry extract showed
      that the air and extract feed rates did not significantly affect (25% level) the
      caffeine content, but that drying temperature is a major factor to consider when
      the extract is submitted to fluid bed drying. Caffeine losses were significant
      (1% level) for drying temperatures above 120 degrees C, while moisture content
      was lower than 3% for temperatures above 120 degrees C. The data showed that
      there is an optimum temperature for the drying of guarana extracts in spouted
      beds, and under the conditions used in this study it was 120 degrees C.

PMID- 16796372
TI  - Formulation and optimization of mouth dissolve tablets containing rofecoxib solid
      dispersion.
AB  - The purpose of the present investigation was to increase the solubility and
      dissolution rate of rofecoxib by the preparation of its solid dispersion with
      polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug
      polymer interactions were investigated using differential scanning calorimetry
      (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy
      (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid
      dispersion with PVP K30 was used with various disintegrants and sublimable
      materials. In an attempt to construct a statistical model for the prediction of
      disintegration time and percentage friability, a 3(2) randomized full and reduced
      factorial design was used to optimize the influence of the amounts of
      superdisintegrant and subliming agent. The obtained results showed that
      dispersion of the drug in the polymer considerably enhanced the dissolution rate.
      The drug-to-carrier ratio was the controlling factor for dissolution improvement.
      FTIR spectra revealed no chemical incompatibility between the drug and PVP K30.
      As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which
      explains the better dissolution rate of the drug from its solid dispersions.
      Concerning the optimization study, the multiple regression analysis revealed that
      an optimum concentration of camphor and a higher percentage of crospovidone are
      required for obtaining rapidly disintegrating tablets. In conclusion, this
      investigation demonstrated the potential of experimental design in understanding
      the effect of the formulation variables on the quality of mouth dissolve tablets
      containing solid dispersion of a hydrophobic drug.

PMID- 16796375
TI  - Tumoricidal effects of etoposide incorporated into solid lipid nanoparticles
      after intraperitoneal administration in Dalton's lymphoma bearing mice.
AB  - The tumoricidal effects of etoposide incorporated into lipid nanoparticles after
      single-dose administration were investigated in Dalton's lymphoma ascites bearing
      mice. Etoposide and its nanoparticle formulations were administered
      intraperitoneally, and the cell cycle perturbation, cytogenetic damage, cell
      death (apoptosis), tumor regression, and animal survival were investigated as
      parameters of response with time. The tumor burden of mice treated with etoposide
      and its nanoparticle formulations decreased significantly (P < .001) compared
      with the initial up to 4 to 6 days, followed by an increase at later time
      intervals. Of the 3 different formulations, the survival time of mice was higher
      when treated with etoposide-loaded tripalmitin (ETP) nanoparticles, followed by
      etoposide-loaded glycerol monostearate (EGMS) (27.3%) and etoposide-loaded
      glycerol distearate (EGDS) (27.3%) compared with free etoposide. Cell cycle
      analysis revealed the hypodiploid peak (sub G0/G1 cell population) as well as G2
      arrest in mice treated with etoposide and its nanoparticle formulations. The
      frequency of dead cells treated with the nanoparticle formulations remained high
      even after 8 days of treatment compared with free etoposide. The mice treated
      with nanoparticle formulations exhibited hypodiploid peaks and reduced S phase
      even 8 days after treatment, whereas the free etoposide-treated mice showed
      decrease in apoptosis after 3 days of treatment. The apoptotic frequency in cells
      17 days after treatment was in the order of ETP > EGMS > EGDS > etoposide. The
      experimental results indicated that among the 3 nanoparticle formulations
      studied, the ETP nanoparticles showed greater and prolonged apoptotic induction
      properties, resulting in the higher increase in survival time of tumor bearing
      mice.

PMID- 16796373
TI  - Microdialysis as a tool in local pharmacodynamics.
AB  - In many cases the clinical outcome of therapy needs to be determined by the drug
      concentration in the tissue compartment in which the pharmacological effect
      occurs rather than in the plasma. Microdialysis is an in vivo technique that
      allows direct measurement of unbound tissue concentrations and permits monitoring
      of the biochemical and physiological effects of drugs throughout the body.
      Microdialysis was first used in pharmacodynamic research to study
      neurotransmission, and this remains its most common application in the field. In
      this review, we give an overview of the principles, techniques, and applications
      of microdialysis in pharmacodynamic studies of local physiological events,
      including measurement of endogenous substances such as acetylcholine,
      catecholamines, serotonin, amino acids, peptides, glucose, lactate, glycerol, and
      hormones. Microdialysis coupled with systemic drug administration also permits
      the more intensive examination of the pharmacotherapeutic effect of drugs on
      extracellular levels of endogenous substances in peripheral compartments and
      blood. Selected examples of the physiological effects and mechanisms of action of
      drugs are also discussed, as are the advantages and limitations of this method.
      It is concluded that microdialysis is a reliable technique for the measurement of
      local events, which makes it an attractive tool for local pharmacodynamic
      research.

PMID- 16796374
TI  - Drug discovery from natural sources.
AB  - Organic compounds from terrestrial and marine organisms have extensive past and
      present use in the treatment of many diseases and serve as compounds of interest
      both in their natural form and as templates for synthetic modification. Over 20
      new drugs launched on the market between 2000 and 2005, originating from
      terrestrial plants, terrestrial microorganisms, marine organisms, and terrestrial
      vertebrates and invertebrates, are described. These approved substances,
      representative of very wide chemical diversity, together with several other
      natural products or their analogs undergoing clinical trials, continue to
      demonstrate the importance of compounds from natural sources in modern drug
      discovery efforts.

PMID- 16796376
TI  - Microdialysis versus other techniques for the clinical assessment of in vivo
      tissue drug distribution.
AB  - Quantification of target site pharmacokinetics (PK) is crucial for drug discovery
      and development. Clinical microdialysis (MD) has increasingly been employed for
      the description of drug distribution and receptor phase PK of the unbound
      fraction of various analytes. Costs for MD experiments are comparably low and
      given suitable analytics, target tissue PK of virtually any drug molecule can be
      quantified. The major limitation of MD stems from the fact that organs such as
      brain, lung or liver are not readily accessible without surgery. Recently, non
      invasive imaging techniques, i.e. positron emission tomography (PET) or magnetic
      resonance spectroscopy (MRS), have become available for in vivo drug distribution
      assessment and allow for drug concentration measurements in practically every
      human organ. Spatial resolution of MRS imaging, however, is low and although PET
      enables monitoring of regional drug concentration differences with a spatial
      resolution of a few millimetres, discrimination between bound and unbound drug or
      parent compound and metabolite is difficult. Radiotracer development is
      furthermore time and labour intensive and requires special expertise and
      radiation exposure and costs originating from running a PET facility cannot be
      neglected. The recent complementary use of MD and imaging has permitted to
      exploit individual strengths of these diverse techniques. In conclusion, MD and
      imaging techniques have provided drug distribution data that have so far not been
      available. Used alone or in combination, these methods may potentially play an
      important role in future drug research and development with the potential to
      serve as translational tools for clinical decision making.

PMID- 16796378
TI  - Cell-permeable, mitochondrial-targeted, peptide antioxidants.
AB  - Cellular oxidative injury has been implicated in aging and a wide array of
      clinical disorders including ischemia-reperfusion injury; neurodegenerative
      diseases; diabetes; inflammatory diseases such as atherosclerosis, arthritis, and
      hepatitis; and drug-induced toxicity. However, available antioxidants have not
      proven to be particularly effective against many of these disorders. A
      possibility is that some of the antioxidants do not reach the relevant sites of
      free radical generation, especially if mitochondria are the primary source of
      reactive oxygen species (ROS). The SS (Szeto-Schiller) peptide antioxidants
      represent a novel approach with targeted delivery of antioxidants to the inner
      mitochondrial membrane. The structural motif of these SS peptides centers on
      alternating aromatic residues and basic amino acids (aromatic-cationic peptides).
      These SS peptides can scavenge hydrogen peroxide and peroxynitrite and inhibit
      lipid peroxidation. Their antioxidant action can be attributed to the tyrosine or
      dimethyltyrosine residue. By reducing mitochondrial ROS, these peptides inhibit
      mitochondrial permeability transition and cytochrome c release, thus preventing
      oxidant-induced cell death. Because these peptides concentrate >1000-fold in the
      inner mitochondrial membrane, they prevent oxidative cell death with EC50 in the
      nM range. Preclinical studies support their potential use for ischemia
      reperfusion injury and neurodegenerative disorders. Although peptides have often
      been considered to be poor drug candidates, these small peptides have excellent
      "druggable" properties, making them promising agents for many diseases with unmet
      needs.

PMID- 16796377
TI  - Cannabinoids, electrophysiology, and retrograde messengers: challenges for the
      next 5 years.
AB  - Most of the behavioral effects of cannabis and its active ingredients, the
      cannabinoids (delta9THC being the most abundant of these), appear to be mediated
      by cannabinoid receptors. Endogenous cannabinoids (endocannabinoids) are lipid
      mediators that activate these same cannabinoid receptors. Elegant work from
      several laboratories over the past 5 years has established that endocannabinoids,
      possibly acting as retrograde messengers, mediate several forms of neuronal
      plasticity. Endocannabinoid-mediated neuronal plasticity is common, apparently
      occurring at all neurons that express cannabinoid receptors. Thus, it is likely
      that delta9THC produces its effects by interacting with endocannabinoid-mediated
      neuronal plasticity, though whether it does so cooperatively or antagonistically
      remains an open question. In this review we will briefly discuss the work
      establishing endocannabinoids as mediators of neuronal plasticity and then
      present evidence that a major effect of delta9THC may be to antagonize the
      actions of endocannabinoids.

PMID- 16796379
TI  - Lipid mediator informatics-lipidomics: novel pathways in mapping resolution.
AB  - Lipidomics, the systematic decoding of lipid-based information in biosystems, is
      composed of identifying and profiling lipids and lipid-derived mediators. As
      currently practiced, lipidomics can be subdivided into architecture/membrane
      lipidomics and mediator lipidomics. The mapping of structural components and
      their relation to cell activation as well as generation of potent lipid mediators
      and networks involves a mass spectrometry-computational approach so that
      interrelationships and complex mediator networks important for cell homeostasis
      can be appreciated. Cell membranes are composed of a bilayer that contains
      phospholipids, fatty acids, integral membrane proteins, membrane-associated
      proteins, sphingolipids, and so on. The membrane composition of many cell types
      has been established. The components' organization and effect on cell function
      remains to be established, however, and is a quest for lipidomics. Here, we
      review liquid chromatography tandem mass spectrometry-based lipidomic analyses to
      address bioactive lipid mediators in signaling pathways and the roles of lipid
      derived mediators in resolution of inflammation.

PMID- 16796381
TI  - An automated process for building reliable and optimal in vitro/in vivo
      correlation models based on Monte Carlo simulations.
AB  - Many mathematical models have been proposed for establishing an in vitro/in vivo
      correlation (IVIVC). The traditional IVIVC model building process consists of 5
      steps: deconvolution, model fitting, convolution, prediction error evaluation,
      and cross-validation. This is a time-consuming process and typically a few models
      at most are tested for any given data set. The objectives of this work were to
      (1) propose a statistical tool to screen models for further development of an
      IVIVC, (2) evaluate the performance of each model under different circumstances,
      and (3) investigate the effectiveness of common statistical model selection
      criteria for choosing IVIVC models. A computer program was developed to explore
      which model(s) would be most likely to work well with a random variation from the
      original formulation. The process used Monte Carlo simulation techniques to build
      IVIVC models. Data-based model selection criteria (Akaike Information Criteria
      [AIC], R2) and the probability of passing the Food and Drug Administration
      "prediction error" requirement was calculated. To illustrate this approach,
      several real data sets representing a broad range of release profiles are used to
      illustrate the process and to demonstrate the advantages of this automated
      process over the traditional approach. The Hixson-Crowell and Weibull models were
      often preferred over the linear. When evaluating whether a Level A IVIVC model
      was possible, the model selection criteria AIC generally selected the best model.
      We believe that the approach we proposed may be a rapid tool to determine which
      IVIVC model (if any) is the most applicable.

PMID- 16796380
TI  - Cannabinoid receptors and endocannabinoids: evidence for new players.
AB  - It is now well established that the psychoactive effects of Cannabis sativa are
      primarily mediated through neuronal CB1 receptors, while its therapeutic immune
      properties are primarily mediated through CB2 receptors. Two endocannabinoids,
      arachidonoylethanolamide and 2-arachidonoylglycerol, have been identified, their
      action on CB1 and CB2 thoroughly characterized, and their production and
      inactivation elucidated. However, many significant exceptions to these rules
      exist. Here we review the evidence suggesting that cannabinoids can modulate
      synaptic transmission, the cardiovascular system, and the immune system through
      receptors distinct from CB1 and CB2, and that an additional "independent"
      endocannabinoid signaling system that involves palmitoylethanolamide may exist.

PMID- 16796382
TI  - Lipids and lipidomics in brain injury and diseases.
AB  - Lipidomics is systems-level analysis and characterization of lipids and their
      interacting moieties. The amount of information in the genomic and proteomic
      fields is greater than that in the lipidomics field, because of the complex
      nature of lipids and the limitations of tools for analysis. The main innovation
      during recent years that has spurred advances in lipid analysis has been the
      development of new mass spectroscopic techniques, particularly the "soft
      ionization" techniques electrospray ionization and matrix-assisted laser
      desorption/ionization. Lipid metabolism may be of particular importance for the
      central nervous system, as it has a high concentration of lipids. The crucial
      role of lipids in cell signaling and tissue physiology is demonstrated by the
      many neurological disorders, including bipolar disorders and schizophrenia, and
      neurodegenerative diseases such as Alzheimer's, Parkinson's, and Niemann-Pick
      diseases, that involve deregulated lipid metabolism. Altered lipid metabolism is
      also believed to contribute to cerebral ischemic (stroke) injury. Lipidomics will
      provide a molecular signature to a certain pathway or a disease condition.
      Lipidomic analyses (characterizing complex mixtures of lipids and identifying
      previously unknown changes in lipid metabolism) together with RNA silencing,
      using small interfering RNA (siRNA), may provide powerful tools to elucidate the
      specific roles of lipid intermediates in cell signaling and open new
      opportunities for drug development.

PMID- 16796383
TI  - Computational methods in drug design: modeling G protein-coupled receptor
      monomers, dimers, and oligomers.
AB  - G protein-coupled receptors (GPCRs) are membrane proteins that serve as very
      important links through which cellular signal transduction mechanisms are
      activated. Many vital physiological events such as sensory perception, immune
      defense, cell communication, chemotaxis, and neurotransmission are mediated by
      GPCRs. Not surprisingly, GPCRs are major targets for drug development today. Most
      modeling studies in the GPCR field have focused upon the creation of a model of a
      single GPCR (ie, a GPCR monomer) based upon the crystal structure of the Class A
      GPCR, rhodopsin. However, the emerging concept of GPCR dimerization has
      challenged our notions of the monomeric GPCR as functional unit. Recent work has
      shown not only that many GPCRs exist as homo- and heterodimers but also that GPCR
      oligomeric assembly may have important functional roles. This review focuses
      first on methodology for the creation of monomeric GPCR models. Special emphasis
      is given to the identification of localized regions where the structure of a GPCR
      may diverge from that of bovine rhodopsin. The review then focuses on GPCR dimers
      and oligomers and the bioinformatics methods available for identifying homo- and
      heterodimer interfaces.

PMID- 16796384
TI  - Causes and consequences of methamphetamine and MDMA toxicity.
AB  - Methamphetamine (METH) and its derivative 3,4-methylenedioxymethamphetamine
      (MDMA; ecstasy) are 2 substituted amphetamines with very high abuse liability in
      the United States. These amphetamine-like stimulants have been associated with
      loss of multiple markers for dopaminergic and serotonergic terminals in the
      brain. Among other causes, oxidative stress, excitotoxicity and mitochondrial
      dysfunction appear to play a major role in the neurotoxicity produced by the
      substituted amphetamines. The present review will focus on these events and how
      they interact and converge to produce the monoaminergic depletions that are
      typically observed after METH or MDMA administration. In addition, more recently
      identified consequences of METH or MDMA-induced oxidative stress, excitotoxicity,
      and mitochondrial dysfunction are described in relation to the classical markers
      of METH-induced damage to dopamine terminals.

PMID- 16796385
TI  - Role of morphine's metabolites in analgesia: concepts and controversies.
AB  - The metabolites of morphine, morphine-6-glucuronide (M6G) and morphine-3
      glucuronide (M3G), have been extensively studied for their contribution to
      clinical effects following administration of morphine. Those contributions to
      both the desired effect (ie, analgesia) and the undesired effects (eg, nausea,
      respiratory depression) are the subject of clinical controversy. Much attention
      and effort have been directed at investigating the properties of M6G because of
      interest in this substance as a possible substitute for morphine. It exhibits
      increased potency and the possibility of a better side effect profile compared
      with morphine, although the reported relative benefits vary widely. M3G is not
      analgesic, but its role in producing side effects, including the development of
      clinical tolerance, has been proposed. This review is focused on M6G and the
      factors that contribute to its clinical utility. The formation and distribution
      of M6G are presented, as are the analgesic effect and the onset of this effect.
      The impact of genetics, age, and gender on M6G and its effects is also reviewed.

PMID- 16796387
TI  - Interaction of dicaproyl phosphatidylserine with recombinant factor VIII and its
      impact on immunogenicity.
AB  - Replacement therapy with exogenous recombinant factor VIII (rFVIII) to control
      bleeding episodes results in the development of inhibitory antibodies in 15% to
      30% of hemophilia A patients. The inhibitory antibodies are mainly directed
      against specific and universal immunodominant epitopes located in the C2 domain.
      Previously we have shown that complexation of O-phospho-L-serine
      (phosphatidylserine head group) with the phospholipid binding region of the C2
      domain can lead to an overall reduction in the immunogenicity of rFVIII. Here, we
      have investigated the hypothesis that dicaproyl phosphatidylserine, a short-chain
      water-soluble phospholipid, can reduce the immunogenicity of rFVIII. Circular
      dichroism and fluorescence spectroscopy studies suggest that dicaproyl
      phosphatidylserine interacts with rFVIII, causing subtle changes in the tertiary
      and secondary structure of the protein. Sandwich enzyme-linked immunosorbent
      assay studies indicate that dicaproyl phosphatidylserine probably interacts with
      the phospholipid binding region of the C2 domain. The immunogenicity of FVIII
      dicaproyl phosphatidylserine complexes prepared at concentrations above and below
      the critical micellar concentrations of the lipid were evaluated in hemophilia A
      mice. Our results suggest that micellar dicaproyl phosphatidylserine may be
      useful to reduce the immunogenicity of rFVIII preparations.

PMID- 16796386
TI  - Modulating inhibitory ligand-gated ion channels.
AB  - The glycine and gamma-aminobutyric acid receptors (GlyR and GABA(A)R,
      respectively) are the major inhibitory neurotransmitter-gated receptors in the
      central nervous system of animals. Given the important role of these receptors in
      neuronal inhibition, they are prime targets of many therapeutic agents and are
      the object of intense studies aimed at correlating their structure and function.
      In this review, the structure and dynamics of these and other homologous members
      of the nicotinicoid superfamily are described. The modulatory actions of the
      major biological macromolecules that bind and allosterically affect these
      receptors are also discussed.

PMID- 16796388
TI  - In vitro and direct in vivo testing of mixture-based combinatorial libraries for
      the identification of highly active and specific opiate ligands.
AB  - The use of combinatorial libraries for the identification of novel opiate and
      related ligands in opioid receptor assays is reviewed. Case studies involving
      opioid assays used to demonstrate the viability of combinatorial libraries are
      described. The identification of new opioid peptides composed of L-amino acids, D
      amino acids, or L-, D-, and unnatural amino acids is reviewed. New opioid
      compounds have also been identified from peptidomimetic libraries, such as
      peptoids and alkylated dipeptides, and those identified from acyclic (eg,
      polyamine, urea) and heterocyclic (eg, bicyclic guanidine) libraries are
      reviewed.

PMID- 16796389
TI  - Monoclonal antibody form and function: manufacturing the right antibodies for
      treating drug abuse.
AB  - Drug abuse continues to be a major national and worldwide problem, and effective
      treatment strategies are badly needed. Antibodies are promising therapies for the
      treatment of medical problems caused by drug abuse, with several candidates in
      preclinical and early clinical trials. Monoclonal antibodies can be designed that
      have customized affinity and specificity against drugs of abuse, and because
      antibodies can be designed in various forms, in vivo pharmacokinetic
      characteristics can be tailored to suit specific clinical applications (eg, long
      acting for relapse prevention, or short-acting for overdose). Passive
      immunization with antibodies against drugs of abuse has several advantages over
      active immunization, but because large doses of monoclonal antibodies may be
      needed for each patient, efficient antibody production technology is essential.
      In this minireview we discuss some of the antibody forms that may be effective
      clinical treatments for drug abuse, as well as several current and emerging
      production systems that could bridge the gap from discovery to patient use.

PMID- 16796390
TI  - Brain tissue lipidomics: direct probing using matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Lipidomics is the new frontier in biomolecular structural studies. Not only are
      lipids the main components in membranes that define the contours of the cell and
      its organelles, but they are also used for storage. Lipids form stable
      noncovalent complexes with proteins as well as with many drugs. Lipids are a
      storage depot for drugs and certain types of organic molecules. To study lipid
      composition and distribution, complex and time-consuming techniques are used.
      However, recent advances in mass spectrometry, mainly matrix-assisted laser
      desorption/ionization (MALDI) have made it possible to directly probe tissues to
      study structural components, as well as for the localization of drugs. Direct
      tissue imaging is a powerful tool as it gives a more complete and accurate
      structural picture and can trace and follow where drugs localize in tissue with
      minimal anatomical disruption and a minimum of manipulations. Hence, we believe
      that in addition to its accuracy and efficiency, this new approach will lead to a
      better understanding of physiological processes as well as the pathophysiology of
      disease.

PMID- 16796391
TI  - Targeting the PDZ domains of molecular scaffolds of transmembrane ion channels.
AB  - The family of multidomain proteins known as the synaptic associated proteins
      (SAPs) act as molecular scaffolds, playing an important role in the signaling and
      maintenance of several receptors and channels. The SAPs consist of 5 individual
      protein domains: 3 PDZ (PSD95, Disc Large, Zo1) domains, an SH3 domain, and an
      inactive guanyl kinase (GK) domain. The 3 PDZ domains bind the C-termini of
      specific receptors and channels, leading to the transient association with
      cytoskeletal and signaling proteins. Molecules targeting specific domains of the
      SAPs may provide a novel route for the regulation of channel and receptor
      function. Here we describe a structural-based approach for the development of
      such inhibitors for the PDZ domains of SAP90. The high sequence homology of the 3
      domains has necessitated targeting regions outside the canonical binding pocket.
      The structural features of the PDZ domains with the C-termini of different
      receptors (GluR6), channels (Kv1.4), and cytoskeletal proteins (CRIPT) provide
      insight into targeting these regions.

PMID- 16796392
TI  - Discovery pharmaceutics--challenges and opportunities.
AB  - Most pharmaceutical companies are now evaluating compounds for druglike
      properties early in the discovery process. The data generated at these early
      stages allow upfront identification of potential development challenges and thus
      selection of the best candidates for lead nomination. Most often, lead nomination
      candidates are selected based on pharmacological and toxicological data. However,
      many drugs in development suffer from poor biopharmaceutical properties due to
      suboptimal physiochemical parameters. The poor biopharmaceutical properties often
      lead to extended timelines and a higher cost of developing the compounds. To
      avoid these problems and choose the best compounds from a biopharmaceutical
      perspective, physicochemical parameters such as solubility, lipophilicity, and
      stability need to be evaluated as early as possible. Furthermore, the
      preformulation approaches used to evaluate the compounds for their
      pharmacokinetic and toxicological properties need to be optimized. This
      minireview summarizes some of the parameters and approaches that can be used to
      evaluate compounds in the early stages of drug discovery.

PMID- 16796393
TI  - Prescribing aerobic exercise for the regulation of postprandial lipid metabolism
      : current research and recommendations.
AB  - Prolonged presence of elevated plasma triglycerides (TGs) during the postprandial
      period has been suggested to increase the risk for coronary artery disease.
      Aerobic exercise attenuates postprandial lipaemia and this has generally been
      described as a short-term effect of the exercise. Effects of exercise on
      postprandial lipaemia have mostly been investigated, and documented, with large
      exercise-induced energy expenditures (i.e. 1000 kcal). The exact mechanisms
      involved in the attenuation of postprandial lipaemia with exercise are not
      completely understood, but it appears that at least two mechanisms are involved:
      a decrease in TG secretion by the liver and an increase in plasma TG clearance by
      the muscle. Changes in the metabolism of other lipids, such as those in high
      density lipoprotein cholesterol, have been documented only when the exercise is
      performed some hours before the fat meal. Although factors such as the physical
      fitness and percentage body fat of an individual are likely to also be involved,
      the most important factors determining the magnitude of the attenuation in
      postprandial lipaemia appear to be the magnitude of the exercise-induced energy
      expenditure and the intensity of exercise. To date, the evidence suggests that
      healthy individuals can generally induce favourable changes in postprandial
      lipaemia with aerobic exercise that: (i) is completed during the period extending
      from 16 hours before a meal through 1.5 hours after a meal; (ii) is of moderate
      intensity; and (iii) results in an energy expenditure of approximately 500 kcal
      (or more).

PMID- 16796394
TI  - How does exercise affect bone development during growth?
AB  - It is increasingly accepted that osteoporosis is a paediatric issue. The
      prepubertal human skeleton is quite sensitive to the mechanical stimulation
      elicited by physical activity. To achieve the benefits for bone deriving from
      physical activity, it is not necessary to perform high volumes of exercise, since
      a notable osteogenic effect may be achieved with just 3 hours of participation in
      sports. Physical activity or participation in sport should start at prepubertal
      ages and should be maintained through the pubertal development to obtain the
      maximal peak bone mass potentially achievable. Starting physical activity prior
      to the pubertal growth spurt stimulates both bone and skeletal muscle hypertrophy
      to a greater degree than observed with normal growth in non-physically active
      children. High strain-eliciting sport like gymnastics, or participation in sports
      or weight-bearing physical activities like football or handball, are strongly
      recommended to increase the peak bone mass. Moreover, the increase in lean mass
      is the most important predictor for bone mineral mass accrual during prepubertal
      growth throughout the population. Since skeletal muscle is the primary component
      of lean mass, participation in sport could have not only a direct osteogenic
      effect, but also an indirect effect by increasing muscle mass and hence the
      tensions generated on bones during prepubertal years.

PMID- 16796395
TI  - Sports activity after total hip and knee arthroplasty : specific recommendations
      concerning tennis.
AB  - Lower extremity total joint arthroplasties are among the most successful
      operations in orthopaedics. Presently, it appears that some patients wish to not
      only have general functions restored, but also desire the opportunity to return
      or continue on a high level of activity. This review summarises the literature
      concerning athletic activity, and tennis in particular, in relation to lower
      extremity total joint arthroplasties. Orthopaedic surgeons frequently recommend
      participation in low-impact sports such as swimming, walking, bicycling, bowling
      and golf. The patient's return to these recreational activities appears to be
      without problems. In contrast, there has been a general consensus from surgeons
      to avoid high-impact sports such as tennis and jogging after total joint
      arthroplasty, but there have been numerous studies that reported functional
      results being compatible with these activity levels. Conflicts emerge with some
      studies that describe lower survival rates for hip and knee arthroplasty in
      patients participating in high-impact sports. Most of these studies report that
      participation in sporting activities following total joint arthroplasty refers to
      increased polyethylene wear and debris, which could eventually result in implant
      failure. With recent advances in implant technology and surgical technique, the
      survival rates for modern prosthetic designs and patients with these high demands
      are promising. Various studies assessing the association between clinical outcome
      and participation in tennis did not demonstrate a harmful effect on implant
      survival rates. Although the majority of these studies do not reflect a true
      representation of the average patient undergoing total joint arthroplasty, more
      surgeons are confronted with the patients' desire to continue with sports
      activity. To optimise results, patients who demand higher levels of activity must
      be carefully selected, and must have the motivation and drive to optimise their
      results. In general, all patients should be encouraged to remain physically
      active to improve general health, maintain good bone quality, and improve implant
      fixation. There is still a need for prospective, randomised controlled studies
      concerning high activity and its impact on total joint arthroplasty.

PMID- 16796398
TI  - Spectral tuning of localised surface plasmon-polariton resonance in metallic nano
      crescents.
AB  - The utilisation of plasmonic effects in metallic nanostructures is gaining
      importance for applications in molecular sensing. Of special interest is the
      local field enhancement effect, which enables surface-enhanced Raman scattering
      and significantly boosts the sensitivity of the Raman technique. For in vivo
      biological research, the ability to excite the resonance of localised surface
      plasmon-polaritons within the biological window is often desired. A new
      nanostructure called the nano-crescent is introduced and exhibits strong
      plasmonic activities within the biological window using a novel intra-particle
      plasmonic coupling scheme.

PMID- 16796397
TI  - Temporal changes in the physical fitness of US Army recruits.
AB  - This article defines physical fitness and then reviews the literature on temporal
      trends in the physical fitness of new US Army recruits. Nineteen papers were
      found that met the review criteria and had published recruit fitness data from
      1975 to 2003. The limited data on recruit muscle strength suggested an increase
      from 1978 to 1998 (20-year period). Data on push-ups and sit-ups suggested no
      change in muscular endurance between 1984 and 2003 (19-year period). Limited data
      suggested that maximal oxygen uptake (VO2max) [mL/kg/min] of male recruits did
      not change from 1975 to 1998 (23-year period), while there was some indication of
      a small increase in female recruit VO2max in the same period. On the other hand,
      slower times on 1-mile (1.6km) and 2-mile (3.2km) runs indicate declines in
      aerobic performance from 1987 to 2003 (16-year period). The apparent discrepancy
      between the VO2max and endurance running data may indicate that recruits are not
      as proficient at applying their aerobic capability to performance tasks, such as
      timed runs, possibly because of factors such as increased bodyweight, reduced
      experience with running, lower motivation and/or environmental factors. Recruit
      height, weight and body mass index have progressively increased between 1978 and
      2003 (25-year period). Both the body fat and fat-free mass of male recruits
      increased from 1978 to 1998 (20-year period); however, body composition data on
      female recruits did not show a consistent trend. In this same time period, the
      literature contained little data on youth physical activity but there was some
      suggestion that caloric consumption increased. This article indicates that
      temporal trends in recruit fitness differ depending on the fitness component
      measured. The very limited comparable data on civilian populations showed trends
      similar to the recruit data.

PMID- 16796399
TI  - Electrophoretic analysis of gold nanoparticles: size-dependent electrophoretic
      mobility of nanoparticles.
AB  - Efforts were made to realise a two-dimensional, on-line-coupled isotachophoresis
      capillary zone electrophoresis system. The electrophoretic behaviour of gold
      nanoparticles was investigated with the idea that they could be used to improve
      the control of this electrophoretic set-up. The well-known citrate-ligated gold
      nanoparticles were not suitable for this application, because the ligand was
      desorbed, and the nanoparticle solutions were degraded. Therefore
      mercaptocarboxylic acids were used, because the chemisorption of thiols on the
      gold surface was improved. Isotachophoretic measurements were carried out with
      these nanoparticles. A size-dependent electrophoretic mobility was found
      according to theoretical predictions, and the surface and zeta-potential were
      discussed for the small particle range. A new method for concentration
      measurements of nanoparticles is presented by means of isotachophoresis.

PMID- 16796400
TI  - Fluorogenic nanocrystals for highly sensitive detection of C-reactive protein.
AB  - A solid-phase sandwich fluorescence immunoassay using nanocrystals of a
      fluorogenic precursor, fluorescein diacetate (FDA), conjugated with monoclonal
      antibodies for the detection of C-reactive protein (CRP), is described. FDA
      nanocrystals were coated with distearoylglycerophosphoethanolamine (DSPE),
      modified with amino(poly(ethylene glycol))(PEG(2000)-Amine) as an interface for
      coupling biomolecules. CRP was chosen as a model analyte because of its widely
      accepted role as a marker for acute inflammation and prospective heart failure. A
      low limit of detection (1.10 microg l(-1)) and high precision (CV = 2.72-9.48%)
      were achieved. Following the immunoreaction, the monoclonal anti-CRP conjugated
      nanocrystals were released by hydrolysis and dissolution instigated by the
      addition of a large volume of organic solvent-sodium hydroxide mixture. Using
      human serum samples from 66 patients with high heart attack risk and 19 healthy
      blood donors, this CRP fluorescence immunoassay showed a good correlation to the
      commercially available, turbidimetric immunoassay for CRP. This result was
      corroborated by the Bland-Altman plot that showed a mean difference between the
      two methods of only 0.36+/-1.46 mg l(-1). The study demonstrates that the organic
      fluorogenic FDA nanocrystals can be applied for the detection of CRP, which is a
      clinically interesting plasma protein with a low limit of detection.

PMID- 16796396
TI  - The pathomechanics of plantar fasciitis.
AB  - Plantar fasciitis is a musculoskeletal disorder primarily affecting the fascial
      enthesis. Although poorly understood, the development of plantar fasciitis is
      thought to have a mechanical origin. In particular, pes planus foot types and
      lower-limb biomechanics that result in a lowered medial longitudinal arch are
      thought to create excessive tensile strain within the fascia, producing
      microscopic tears and chronic inflammation. However, contrary to clinical
      doctrine, histological evidence does not support this concept, with inflammation
      rarely observed in chronic plantar fasciitis. Similarly, scientific support for
      the role of arch mechanics in the development of plantar fasciitis is equivocal,
      despite an abundance of anecdotal evidence indicating a causal link between arch
      function and heel pain. This may, in part, reflect the difficulty in measuring
      arch mechanics in vivo. However, it may also indicate that tensile failure is not
      a predominant feature in the pathomechanics of plantar fasciitis. Alternative
      mechanisms including 'stress-shielding', vascular and metabolic disturbances, the
      formation of free radicals, hyperthermia and genetic factors have also been
      linked to degenerative change in connective tissues. Further research is needed
      to ascertain the importance of such factors in the development of plantar
      fasciitis.

PMID- 16796401
TI  - Human monoclonal antibody combination against SARS coronavirus: synergy and
      coverage of escape mutants.
AB  - BACKGROUND: Experimental animal data show that protection against severe acute
      respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal
      antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans,
      broad coverage of different strains of SARS-CoV and control of potential
      neutralization escape variants will be required. Combinations of virus
      neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS:
      Human mAb CR3014 has been shown to completely prevent lung pathology and abolish
      pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS
      CoV variants escaping neutralization by CR3014, which all had a single P462L
      mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments
      confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues
      318-510) harboring this mutation was abolished. We therefore screened an antibody
      phage library derived from blood of a convalescent SARS patient for antibodies
      complementary to CR3014. A novel mAb, CR3022, was identified that neutralized
      CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1
      fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like
      strain SZ3. No escape variants could be generated with CR3022. The mixture of
      both mAbs showed neutralization of SARS-CoV in a synergistic fashion by
      recognizing different epitopes on the receptor-binding domain. Dose reduction
      indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at
      100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing
      antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies
      do not convert the abortive infection of primary human macrophages by SARS-CoV
      into a productive one. CONCLUSIONS: The combination of two noncompeting human
      mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth
      of protection. At the same time, synergy between CR3014 and CR3022 may allow for
      a lower total antibody dose to be administered for passive immune prophylaxis of
      SARS-CoV infection.

PMID- 16796402
TI  - Uptake of workplace HIV counselling and testing: a cluster-randomised trial in
      Zimbabwe.
AB  - BACKGROUND: HIV counselling and testing is a key component of both HIV care and
      HIV prevention, but uptake is currently low. We investigated the impact of rapid
      HIV testing at the workplace on uptake of voluntary counselling and testing
      (VCT). METHODS AND FINDINGS: The study was a cluster-randomised trial of two VCT
      strategies, with business occupational health clinics as the unit of
      randomisation. VCT was directly offered to all employees, followed by 2 y of open
      access to VCT and basic HIV care. Businesses were randomised to either on-site
      rapid HIV testing at their occupational clinic (11 businesses) or to vouchers for
      off-site VCT at a chain of free-standing centres also using rapid tests (11
      businesses). Baseline anonymised HIV serology was requested from all employees.
      HIV prevalence was 19.8% and 18.4%, respectively, at businesses randomised to on
      site and off-site VCT. In total, 1,957 of 3,950 employees at clinics randomised
      to on-site testing had VCT (mean uptake by site 51.1%) compared to 586 of 3,532
      employees taking vouchers at clinics randomised to off-site testing (mean uptake
      by site 19.2%). The risk ratio for on-site VCT compared to voucher uptake was 2.8
      (95% confidence interval 1.8 to 3.8) after adjustment for potential confounders.
      Only 125 employees (mean uptake by site 4.3%) reported using their voucher, so
      that the true adjusted risk ratio for on-site compared to off-site VCT may have
      been as high as 12.5 (95% confidence interval 8.2 to 16.8). CONCLUSIONS: High
      impact VCT strategies are urgently needed to maximise HIV prevention and access
      to care in Africa. VCT at the workplace offers the potential for high uptake when
      offered on-site and linked to basic HIV care. Convenience and accessibility
      appear to have critical roles in the acceptability of community-based VCT.

PMID- 16796403
TI  - Cost-effectiveness of treating multidrug-resistant tuberculosis.
AB  - BACKGROUND: Despite the existence of effective drug treatments, tuberculosis (TB)
      causes 2 million deaths annually worldwide. Effective treatment is complicated by
      multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs.
      We projected the health benefits and cost-effectiveness of using drug
      susceptibility testing and second-line drugs in a lower-middle-income setting
      with high levels of MDR TB. METHODS AND FINDINGS: We developed a dynamic state
      transition model of TB. In a base case analysis, the model was calibrated to
      approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence
      of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses
      considered other settings. The following strategies were evaluated: first-line
      drugs administered under directly observed therapy (DOTS), locally standardized
      second-line drugs for previously treated cases (STR1), locally standardized
      second-line drugs for previously treated cases with test-confirmed MDR TB (STR2),
      comprehensive drug susceptibility testing and individualized treatment for
      previously treated cases (ITR1), and comprehensive drug susceptibility testing
      and individualized treatment for all cases (ITR2). Outcomes were costs per TB
      death averted and costs per quality-adjusted life year (QALY) gained. We found
      that strategies incorporating the use of second-line drug regimens following
      first-line treatment failure were highly cost-effective compared to strategies
      using first-line drugs only. In our base case, standardized second-line treatment
      for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of
      720 dollars per QALY (8,700 dollars per averted death) compared to DOTS.
      Individualized second-line drug treatment for MDR TB following first-line failure
      (ITR1) provided more benefit at an incremental cost of 990 dollars per QALY
      (12,000 dollars per averted death) compared to STR2. A more aggressive version of
      the individualized treatment strategy (ITR2), in which both new and previously
      treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio
      of 11,000 dollars per QALY (160,000 dollars per averted death) compared to ITR1.
      The STR2 and ITR1 strategies remained cost-effective under a wide range of
      alternative assumptions about treatment costs, effectiveness, MDR TB prevalence,
      and transmission. CONCLUSIONS: Treatment of MDR TB using second-line drugs is
      highly cost-effective in Peru. In other settings, the attractiveness of
      strategies using second-line drugs will depend on TB incidence, MDR burden, and
      the available budget, but simulation results suggest that individualized regimens
      would be cost-effective in a wide range of situations.

PMID- 16796405
TI  - [The term osteopenia and risk of fracture].

PMID- 16796404
TI  - Advice from a medical expert through the Internet on queries about AIDS and
      hepatitis: analysis of a pilot experiment.
AB  - BACKGROUND: Advice from a medical expert on concerns and queries expressed
      anonymously through the Internet by patients and later posted on the Web, offers
      a new type of patient-doctor relationship. The aim of the current study was to
      perform a descriptive analysis of questions about AIDS and hepatitis made to an
      infectious disease expert and sent through the Internet to a consumer-oriented
      Web site in the Spanish language. METHODS AND FINDINGS: Questions were e-mailed
      and the questions and answers were posted anonymously in the "expert-advice"
      section of a Web site focused on AIDS and hepatitis. We performed a descriptive
      study and a temporal analysis of the questions received in the first 12 months
      after the launch of the site. A total of 899 questions were received from
      December 2003 to November 2004, with a marked linear growth pattern. Questions
      originated in Spain in 68% of cases and 32% came from Latin America (the
      Caribbean, Central America, and South America). Eighty percent of the senders
      were male. Most of the questions concerned HIV infection (79%) with many fewer on
      hepatitis (17%). The highest numbers of questions were submitted just after the
      weekend (37% of questions were made on Mondays and Tuesdays). Risk factors for
      contracting HIV infection were the most frequent concern (69%), followed by the
      window period for detection (12.6%), laboratory results (5.9%), symptoms (4.7%),
      diagnosis (2.7%), and treatment (2.2%). CONCLUSIONS: Our results confirm a great
      demand for this type of "ask-the-expert" Internet service, at least for AIDS and
      hepatitis. Factors such as anonymity, free access, and immediate answers have
      been key factors in its success.

PMID- 16796406
TI  - [Prevalence of methylenetetrahydrofolate reductase C677T mutation among patients
      with acute ischemic cerebrovascular disease in Aragon].
AB  - BACKGROUND: Mutation C677T of the methylenetetrahydrofolate reductase (MTHFR) is
      the main cause of mild hyperhomocysteinemia. Hyperhomocysteinemia is a recognized
      risk factor for aterothrombosis. MTHFR C677T patients have higher levels of
      homocysteine in absence of dietary folates. METHODS: Retrospective study over
      data from patients studied for MTHFR C677T diagnosed of ischemic stroke (IS)
      younger 50 or older 50 without classic vascular risk factors or with familiar or
      personal history suggesting thrombophilia in a period of 3 years. MTHFR C677T was
      screened in 90 healthy blood donors as a control group. Computer database was
      used for descriptive statistics. RESULTS: Blood samples from 99 patients and from
      90 donors (control). Mean age: 44.3 with Standard deviation (SD) 13.9 years in IS
      group and 39.1 with SD 8.3 years in control group. We found 19 (19.19%)
      homozygotes for MTHFR C677T in IS group and 14 (15.55%) in control group.
      CONCLUSIONS: Homozygosis for MTHFR C667T is more frequent in the IS group than in
      the control one, although there is no significant differences. Anyway, we suggest
      that, because of the high prevalence of the mutation MTHFR C677T found, screening
      should be made in the thombophilia studies, so that we could find patients with a
      risk factor that could be lowered by folates in the diet.

PMID- 16796407
TI  - [Effect of atorvastatin on Fas (CD95/Apo-1) expression in normal or ischemic
      brain].
AB  - BACKGROUND: The physiopathology of the brain ischemia includes many events such
      as important apoptotic mechanisms were Fas protein is expressed. Statins have
      neuroprotector effects that are independent of their blood lipid reducing
      actions. OBJECTIVE: Study of the atorvastatin effect on Fas expression in brain
      ischemia. MATERIAL AND METHODS: Fifteen male Sprague Dawley rats were distributed
      in three groups (n=5), the control group without cerebral ischemia, in the other
      two experimental groups (1 and 2) a global cerebral ischemia were induced by
      respiratory arrest (D-tubocurarin). Experimental group 2 was treated with
      atorvastatin (10 mg/Kg/d, p.o.) during two weeks before the induction of the
      ischemia. Immunohistochemical study of brain frontal specimens was done by the
      Avidin-Biotin-Peroxidase method. RESULTS: Fas was expressed in 38% of cells in
      non ischemic brain, this expression increased to 63% of cells in ischemic brain
      samples (P = 0.0003) Fas expression in ischemia was significantly inhibited by
      atorvastatin in 23% (P = 0.0007). CONCLUSIONS: Atorvastatin decreased Fas
      expression in ischemic brain. This fact must be taken into account to explain the
      atorvastatin neuroprotection and suggests the potential use such as primary
      prevention for ischemic attacks.

PMID- 16796408
TI  - [Tuberculosis in the elderly in a general hospital in the Region of Madrid, 1994
      2003].
AB  - INTRODUCTION: Tuberculosis in the elderly is a health problem that is on the
      increase nowadays in industrialised countries. The aim of this study is to
      describe epidemiological, clinical and microbiological characteristics of
      tuberculosis in elderly patients in a general hospital in the Region of Madrid
      from 1994 to 2003. METHODS: Only microbiologically and/or histopathologically
      confirmed tuberculosis were studied. Epidemiological, clinical and
      microbiological variables were analyzed. Microbiological and histopathological
      laboratory results and medical records were collected. RESULTS: The proportion of
      cases occurring among the elderly rose from 12.4% between 1994 and 1998 to 17.8%
      between 1999 and 2003 (p <0.05). A total of 160 tuberculosis cases were studied:
      92.5% were microbiologically (culture) confirmed and 7.5% histopathologically
      confirmed. The average time to culture positivity was 18.8 days (SD: 6.5). 88.7%
      isolates were susceptible to streptomycin, isoniazid, rifampin, ethambutol, and
      pyrazinamide. The main locations of tuberculosis were pulmonary (59.4%),
      ganglionary (11.9%) and genitourinary (10.0%). A positive smear in the sputum was
      discovered for 52.6% of pulmonary tuberculosis. The most prevalent risk factors
      were immunosuppression (14.8%) and diabetes mellitus (12.3%). Neither of them
      were VIH, intravenous drug users or immigrants. 50.7% cases were hospitalized.
      CONCLUSIONS: Tuberculosis in the elderly is on the increase in our region
      nowadays. The epidemiological pattern of tuberculosis in the elderly differs from
      that observed in younger patients. Therefore specific control and prevention
      strategies are needed in order to reduce tuberculosis incidence in aged
      populations.

PMID- 16796409
TI  - [Study of hypertensive very elderly population admitted to a regional hospital].
AB  - OBJECTIVES: To analyse the characteristics of the hospitalized very elderly
      people (age equal or superior to 80 years) with hypertension (HT). PATIENTS AND
      METHODS: Prospective study including the patients with HT who need
      hospitalization in our medical institution. Data collected were: demographic,
      clinical parameters, factors of vascular risk, hygienic-dietetic strategies,
      pharmacological treatment, cause of hospitalization, and biochemical
      determinations. RESULTS: There were included 92 very elderly patients (71 women);
      they represent 14 % of total hospitalized people. Two third parts had not
      realized academic studies, being 60 % of rural origin. Almost the half (41 %) was
      diabetic, and 27 % had dyslipidemia. Overall 62 % had 4 or more factors of
      cardiovascular risk. The hospitalization was related to the HT in the half of the
      cases, and 61 % had already previously some cardiovascular event. The lifestyle
      modifications more frequent were: not to smoke (95 %), no alcohol (81 %), and
      diet without salt (75 %). Diuretics were the most frequent anti-hypertensive
      agent used. The global mortality was two times superior to the hypertensive
      population < 80 years in the same period. CONCLUSIONS: The very elderly
      hypertensive patients of our study are fundamentally women, of rural origin and
      without academic studies. The above mentioned hospitalization is attributable
      directly to the HT in the half of the cases. They are a population of high
      cardiovascular risk, with previous events cardiac and cerebral-vascular. They
      confess to realize frequently the hygienic-dietetic strategies recommended. The
      diuretics are the anti-hypertensive agents most used for the HT. Since it was of
      waiting for the mortality in this group it is high.

PMID- 16796410
TI  - [Kikuchi-Fujimoto disease: review of four cases].
AB  - Kikuchi-Fujimoto disease is an uncommon form of lymphadenitis, firstly described
      in Japan. Etiology is unknown. It affects mainly young women. It commonly
      manifests as a painful cervical lymphadenitis usually associated with fever and
      leukopenia. Clinical course users to be benign, leading spontaneously to a
      complete recovery. Histological findings include necrotizing changes with
      cariorrhesis, partial loss of ganglionar architecture and foci of histiocytic
      infiltrates in the cortical and/or paracortical zones of the lymph nodes. A
      common finding is the absence of neutrophil granulocytes in the inflammatory
      infiltrates, in contrast to other necrotizing lymphadenitis. We report four cases
      of Kikuchi-Fujimoto disease, recently identified in our hospital.

PMID- 16796411
TI  - [Bilateral chylothorax in a case of metastatic adenocarcinoma of unknown
      primary].
AB  - We present a case of bilateral chylothorax and lung carcinomatous lymphangitis.
      Clinical evolution was unfavorable, leading to death due to respiratory
      insufficiency. Necropsy showed widespread metastatic adenocarcinoma of unknown
      primary. From this case, we review the etiology, diagnosis and therapeutic
      options available in chylothorax.

PMID- 16796412
TI  - [Chagasic myocardiopathy: an infectious etiology of congestive heart failure].
AB  - We present a case report of a Latin-American patient with dilated cardiomyopathy
      due to chronic Chagas disease satisfactorily treated with usual cardiologic
      support. We report a new aetiology of heart failure which is uncommon in our
      country but could rise due to immigration from endemic countries.

PMID- 16796413
TI  - [Transient ischemic attack due to Lambl's excrescence. Report of a case and
      review of the literature].
AB  - We describe a 42-year-old man presenting in the emergency department with
      transient ischemic attack without cardiovascular risk factors. Systemic disease
      and hypercoagulability substract was discarded. Only transesophageal
      echocardiography could confirm the presence of a Lambl's excrescence in the
      aortic valve (valvular strand). We review clinical management and new therapeutic
      options in stroke prevention used in this unusual source of cardiac embolism.

PMID- 16796414
TI  - [Septic arthritis as an initial manifestation of bacterial endocarditis caused by
      Staphylococcus aureus].
AB  - We describe a case of Staphylococcus aureus mitral valve endocarditis, in a 80
      year-old man who presented with abrupt onset of septic arthritis of the
      glenohumeral joint, without cardiac symptomatology. Fever and articular infection
      recovery after articular drainage and antimicrobial therapy, but worsening caused
      by heart failure made valve replacement surgery urgent. He died suddenly before
      surgery could be done. Until August 2005, in medical literature (Index Medicus,
      Medline, Embase, Excerpta Medica), we have found 26 cases of bacterial
      endocarditis with articular infection, as initial manifestation, but none with
      septic arthritis and only one in the glenohumeral joint. This report highlights
      that unexplained arthritis should alert us to the possibility of bacterial
      endocarditis because of its influence on the clinical management and prognostic
      implications.

PMID- 16796415
TI  - [Pacemaker endocarditis].
AB  - In the last years an increment has taken place in the pacemaker and implantable
      cardioverter-defibrillator indications that will have as consequence an increase
      of the prevalence of endocarditis associated to intravascular devices, for what
      acquires special relevance for the clinician to know this entity and to include
      it in his differential diagnoses. The objective of this article is to describe
      the epidemiology, clinic characteristics, diagnosis, treatment and outcome of the
      pacemaker endocarditis.

PMID- 16796416
TI  - [Retroperitoneal fibrosis secondary to ergotamine use].

PMID- 16796417
TI  - [Look for, compare, and if you find something better...].

PMID- 16796418
TI  - European and French pharmaceutical market assessed by Prescrire in 2005: mainly
      bogus innovation.

PMID- 16796419
TI  - [A cost-effectiveness study of first-line hormone therapy in post-menopausal
      patients with metastatic breast cancer on neoadjuvant treatment].
AB  - OBJECTIVE: Breast cancer is a hormone-dependent tumor, which expands therapy
      options. The aim of this study was to perform a pharmacoeconomic assessment of
      these drugs in post-menopausal patients with metastatic breast cancer or on
      neoadjuvant therapy. METHOD: To assess the efficacy of both drug classes a meta
      analysis was carried out from papers obtained in a Medline literature search
      (1997 - June 2004) using the following keywords: breast cancer, postmenopausal,
      aromatase inhibitors, antiestrogens, tamoxifen, neoadjuvant. Effectiveness
      parameters included: objective response, percentage with conservative surgery in
      neoadjuvancy; in metastatic breast cancer, time to progression. Costs were
      considered from drug acquisition data. To determine result strength a sensitivity
      analysis was undertaken, with modified costs and effectiveness. RESULTS: Results
      show a higher effectiveness for aromatase inhibitors as compared to
      antiestrogens. In neoadjuvant therapy: 56.38% versus 36% for objective response
      rate, and 47.64% versus 35% for conservative surgery. In metastatic cancer: 9.96
      versus 6.61 months for time to progression (p <or= 0.05). The pharmacoeconomic
      analysis showed that selecting anastrozole represents a cost of 969 euros and 779
      euros per extra effectiveness unit regarding objective response and conservative
      surgery, respectively, whereas in metastatic cancer patients it represents 56,525
      euros per extra effectiveness unit. CONCLUSIONS: Selecting an aromatase inhibitor
      is a valid option in neoadjuvancy, even if such selection would represent a very
      high cost for metastatic cancer.

PMID- 16796420
TI  - [Detection and analysis of adverse drug reactions in a general hospital's
      emergency department].
AB  - OBJECTIVE: To detect and analyze adverse drug reactions (ADR) leading to
      emergency room visits in our hospital, as well as their severity and outcome, and
      medications most commonly involved, from selected alerting diagnoses. METHOD: A
      retrospective study for the period from January 2003 to December 2004, where all
      reports by the emergency department including our wanted diagnoses were reviewed.
      RESULTS: A total of 1,626 reports with alerting diagnoses were found, of which
      444 (27.3%) were confirmed as potential adverse drug reactions. Of 444 cases, 345
      (77.7%) were discharged to their homes and 90 (20%) were admitted. In all, 52.9%
      of adverse drug reactions were considered moderate, and 19.6% were considered
      serious. The major age group involved was that of patients older than 65 years
      (65.1%), and was involved in 83.9% of adverse drug reactions. Drugs most commonly
      involved included insulins (26.1%), diuretics (17.3%), digoxin (10.9%), and oral
      antidiabetics (9.5%). Major organs and systems involved included the endocrine
      system (55.6%), musculoskeletal system (11%) and cardiovascular system (10.8%).
      CONCLUSIONS: Drugs commonly used in clinical practice, including insulins,
      diuretics or oral antidiabetics induce many of the adverse reactions that lead
      patients to visit emergency departments. A closer monitoring of therapies is
      still needed to prevent adverse drug reactions.

PMID- 16796421
TI  - [Prescription errors in patients admitted to an internal medicine department from
      the emergency room].
AB  - OBJECTIVE: To identify and quantify emergency room prescription errors upon
      patient admission in an internal medicine unit, assess their severity and causes,
      and evaluate their potential clinical impact. METHOD: Discrepancies found between
      emergency room and internal medicine unit prescriptions were analyzed by 4th-year
      resident pharmacists. Prescription errors were collected and classified according
      to their severity and potential morbidity, and a medical analysis of service
      value was performed according to Overhage's method. Furthermore, pharmacist
      actions regarding therapeutic regimen optimization are described. RESULTS: Of 177
      patients, 50 had prescription errors, for a total of 141 errors. Seven percent of
      prescriptions had an error. Mean errors per patient amounted to 0.8 (SD 1.51).
      Most commonly involved medications included anti-asthmatic and anti-infectious
      agents, and fluid therapy agents. On severity assessment 12.8% were considered
      severe, and 57.4% were considered significant. The main cause was omission of a
      needed therapy. Potential pharmacotherapeutic morbidity is related to adverse
      effects and cardiovascular disease. Medical assessment considered 12% very
      significant, and 52% significant. Pharmacist actions were directed towards
      effectiveness improvement in 57% of cases, and safety in 43.2% of cases.
      CONCLUSIONS: Emergency departments, as main entry points for patient admission to
      hospital, should be considered a priority in prescription quality improvement
      programs.

PMID- 16796422
TI  - [Analysis and protocolization of rasburicase use in patients with hematologic
      neoplasms].
AB  - OBJECTIVE: To describe the use of rasburicase in adult patients with
      hematological neoplasias and to present a protocol for its administration jointly
      prepared by the hematology and the pharmacy departments based on the scientific
      evidence available. METHOD: Retrospective study that reviews treatments with
      rasburicase administered in a tertiary 800-bed hospital from July 2002 to May
      2004 to adult patients with hematological neoplasias. The following data were
      collected: demographic and clinical data, daily dose of rasburicase and length of
      treatment, plasma levels of creatinine, potassium, phosphate, calcium, LDH, uric
      acid and white blood cell count daily and until 48 hours after administering the
      last dose of rasburicase. RESULTS: Rasburicase was administered to a total of 18
      adult patients (mean age of 57 years; range 27-84; 11 men and 7 women). Prior to
      treatment, 16 patient had high levels of LDH, 12 patients had a blood count over
      50,000 white blood cells/mm3, and 11 had serum levels of uric acid above 7 mg/dl.
      The dose of rasburicase administered was 0.2 mg/kg/day and the median length of
      treatment was 5 days (range 1-10). The levels of uric acid returned to normal
      values in all patients. Furthermore, an statistically significant decrease of
      creatinine levels was observed. The other biochemical parameters studied were
      duly controlled throughout the treatment. CONCLUSIONS: A high variability is
      observed in the use of rasburicase in our patients. The hematology and pharmacy
      services have been working jointly to prepare a consensus-based protocol
      according to which, depending on the patient s risk of developing TLS (tumoral
      lysis syndrome), standard prophylaxis is administered to low-risk patients
      (intravenous hydration, alopurinol and urine alcalinization) and rasburicase is
      administered initially for 1-3 days to patients with high risk of developing TLS.

PMID- 16796423
TI  - [Assessment of quality as perceived by users of an outpatient pharmaceutical care
      unit].
AB  - OBJECTIVE: To assess quality of care by an Outpatient Pharmaceutical Care Unit
      (OPCU) from patient satisfaction regarding the unit s premises and activities.
      METHOD: A transversal study performed at the OPCU using a patient survey. Patient
      opinions were obtained regarding structural aspects, pharmaceutical care, patient
      information, overall satisfaction, and preference for care in the OPCU or
      pharmacy office. The response variable was the presumed choice for the OPCU or
      traditional pharmacy office. A multivariate analysis using logistic regression
      was used to evaluate the independent effect of variables. RESULTS: In all, 256
      surveys were administered, of which 195 were assessable. Response rate was 76%.
      Responses with highest scores included communication and interaction with
      professionals (4.8 points on average) and care received (4.5 points). Worst
      assessments included OPCU s timetable (3.8 points) and location (3.9 points);
      98.4% of patients were satisfied or very satisfied with care received, and only
      18.4% would switch to the pharmacy office if allowed to. The multivariate
      analysis suggested that variables associated with the pharmacy office choice
      included a negative rating of OPCU s location (OR 9.8, CI 1.3-76.8) and a
      negative rating of information delivered (OR 4.1, CI 1.7-9.8); p < 0.05.
      CONCLUSIONS: Information received and OPCU s location had the greatest impact on
      patient satisfaction. Patient remarks and suggestions were very useful to
      identify areas of improvement, and to introduce modification suiting their views.

PMID- 16796424
TI  - [Quality perceived by outpatients at the pharmaceutical care clinic].
AB  - OBJECTIVE: To know the satisfaction degree manifested by outpatients presenting
      in the hospital pharmacy department pharmaceutical care clinic, and to identify
      organizational improvement items. METHOD: A survey with 8 close-ended questions
      and 1 open-ended question was designed where patients recorded their suggestions
      or comments on the service provided. A sample size of 591 surveys was estimated,
      which allowed to estimate parameters of interest with a 95% confidence interval
      and a +/- 5% accuracy, adjusting by a 40% potential losses percentage. RESULTS:
      Overall response rate was 70%; 23.6% of patients considered that finding the PD
      was difficult or very difficult. Waiting time was normal for 51.8%, but long or
      excessive for 18.4% of patients. Fifty-six percent of individuals considered the
      information received useful or very useful, and 81.1% considered that staff
      friendliness was good or very good. Care timetable was inadequate for 18.1%;
      47.7% pointed out that the attending pharmacist did not identify him or herself.
      Overall satisfaction extent was 7.51 (of 10). A plan for improvement activities
      was designed and implemented regarding: care timetable, pharmacy department
      signaling, and general information on clinic matters. CONCLUSIONS: The survey
      allowed to identify organizational weaknesses. Overall score was very
      satisfactory, yet improvable. Future surveys are required for result comparisons
      and continual improvement assessment.

PMID- 16796425
TI  - [A review of the clinical application of dyes in gastrointestinal
      chromoendoscopy, and their magistral formulation].
AB  - OBJECTIVE: To review the drug compounding of dyes employed in chromoendoscopy,
      and their clinical effectiveness. METHOD: A literature search in Medline,
      Cochrane Library, and Micromedex was carried out with the term chromoendoscopy as
      a keyword, and the search was then repeated for each dye found in association
      with the term endoscopy. A number of monographs, scientific journals, and
      references quoted in selected papers were also reviewed. Papers collected were
      then classified according to their methodology. RESULTS: Ninety-six references
      were found, their original article being recovered for only 57 of these - 13
      clinical trials, 21 case series, and 11 reviews. References were found for 7
      dyes. Main indications, evidence of effectiveness, administration route, and drug
      formulation are described for each dye. CONCLUSIONS: The number of papers
      involved is high, but their accessibility is limited. Evidence is overall scarce,
      but high in cases such as methylene blue for Barrett s esophagus, lugol in the
      detection of esophageal carcinoma, and indigo carmine for colonic hyperplastic
      polyp differentiation. Drug compounding is rather simple, but scarcely developed.

PMID- 16796426
TI  - [Bases of the pharmaceutical care in Hospital Pharmacy].

PMID- 16796427
TI  - [Drug-related clinical research--a practical opportunity for the hospital
      pharmacist].
AB  - OBJECTIVE: To describe a pharmacist s field of activity in drug-related clinical
      trials. METHOD: A non-systematic assessment of available scientific literature in
      international databases queried during the period of May 05 to 31, 2005. RESULTS:
      In all, 36 papers were obtained regarding the role of hospital pharmacists in the
      development of drug-related clinical trials. Most common activities included
      dispensation, storage, and inventory. Participation in ethics committees and
      study coordination represent an expanding area. CONCLUSIONS: Drug-related
      clinical research is an excellent practical setting for the hospital pharmacist.
      Activities related to investigational drug control, including dispensation,
      randomization scheme management, and patient follow-up, are an example. This is a
      novel though rapidly expanding scenario in Brazil.

PMID- 16796428
TI  - [Economical impact of the compassionate treatments on the drug costs in a
      hospital].

PMID- 16796429
TI  - [Elevation of creatine kinase after eccentric exercise in patients treated with
      statins].

PMID- 16796430
TI  - [Asparaginase desensitization in two patients with previous hypersensitivity].

PMID- 16796431
TI  - [Monitoring serum valproic acid concentration in hypoalbuminemic patients].

PMID- 16796432
TI  - Laparoscopic versus open splenectomy for massive splenomegaly: a comparative
      study.
AB  - BACKGROUND: Despite the benefits of the laparoscopic approach to splenectomy, its
      application in patients with massive splenomegaly (splenic weight >or= 1000 g)
      remains controversial. In this study we evaluated the safety and feasibility of
      laparoscopic splenectomy for massive splenomegaly compared with open splenectomy.
      MATERIALS AND METHODS: One surgeon applied the laparoscopic approach to
      splenectomy to all comers with massive splenomegaly, while other surgeons carried
      out the surgery through a laparotomy. The outcomes of the two approaches were
      compared on an intention-to-treat basis. Results of continuous variables are
      shown as medians. RESULTS: Fifteen patients underwent laparoscopic splenectomy
      between 2000 and 2005, and 13 underwent open splenectomy between 1996 and 2003.
      The two groups were comparable for age, sex, American Society of
      Anesthesiologists score, and splenic weight (1.3 vs. 1.1 kg). There was one
      conversion (6.6%) to open surgery. Although laparoscopic splenectomy was
      associated with significantly longer operating time (175 vs. 90 minutes, P <
      0.001), it carried lower postoperative morbidity and mortality (13.3 vs. 30.8%
      and 0 vs. 7.7%, respectively). Laparoscopic splenectomy was associated with
      significantly lower total dose (29 vs. 264 mg morphine-equivalent, P < 0.0001)
      and duration of opiate usage (1 vs. 4 days, P < 0.0001); duration of parenteral
      hydration (24 vs. 96 hours, P = 0.006) and more rapid resumption of oral diet (24
      vs. 72 hours, P = 0.017); and a shorter postoperative hospital stay (3 vs. 10
      days, P < 0.0001). CONCLUSIONS: The laparoscopic approach to splenectomy for
      massive splenomegaly is feasible and safe. Despite a longer operating time, the
      postoperative recovery following laparoscopic splenectomy is smoother, with lower
      morbidity and shorter postoperative hospital stay compared with open splenectomy.

PMID- 16796433
TI  - Operative cholangiography in two-port needlescopic cholecystectomy.
AB  - We report the use of operative cholangiography in two-port needlescopic
      (minilaparoscopic) cholecystectomy. A prospective series of 11 patients underwent
      two-port needlescopic cholecystectomy with operative cholangiography. In ten
      cases, operative cholangiography was successfully performed. There were no
      conversions. No additional ports were required. No related complications were
      noted. Two cases positive for common bile duct stones were identified. The median
      operative time was 92.5 minutes. Operative cholangiography in two-port
      needlescopic cholecystectomy is safe and feasible.

PMID- 16796434
TI  - Simultaneous laparoscopic treatment for rectosigmoid and ileal endometriosis.
AB  - Endometriosis is common in women of childbearing age, while severe intestinal
      endometriosis requiring bowel resection is relatively rare. Intestinal
      endometriosis has recently been managed laparoscopically. We report the case of a
      38-year-old patient with rectosigmoid and ileal endometriosis who was
      successfully treated by laparoscopic bowel resections. The patient had first
      presented at age 34 years with a chief complaint of rectal bleeding and lower
      abdominal pain related to the menstrual cycle. She underwent laparoscopic surgery
      and was diagnosed with severe endometriosis involving the rectosigmoid colon.
      Although an additional laparoscopic surgery had been planned, she did not return
      to the hospital. When she was 38 years old, she presented again with the same
      symptoms. Magnetic resonance imaging revealed a low intensity mass between the
      uterus and the rectosigmoid colon. A barium enema showed a stenotic site in the
      rectosigmoid colon. After hormone therapy, she underwent laparoscopic surgery.
      The anterior wall of the rectosigmoid colon adhered firmly to the corpus of the
      uterus, and another stenotic site was identified at the terminal ileum. The
      rectosigmoid colon and ileum were partially resected under laparoscopy. The
      postoperative course was uneventful and she was freed of symptoms. Laparoscopic
      treatment for patients with severe endometriosis of the bowel has becomes
      feasible and safe.

PMID- 16796435
TI  - Migrating gallstone: from Bouveret's syndrome to distal small bowel obstruction.
AB  - Gallstone ileus is an uncommon cause of small bowel obstruction. When the
      gallstone lodges inside the duodenum and causes gastric outlet obstruction, it is
      termed Bouveret's syndrome. However, it is rather unusual to seen the evolution
      of a migrating gallstone (from duodenum to distal small bowel) in a patient
      during the same hospital admission. We report a case of gallstone ileus from the
      initial presentation of gastric outlet obstruction to the development of distal
      small bowel obstruction within the same hospital admission, and its total
      laparoscopic treatment.

PMID- 16796436
TI  - Transperitoneal, transmesocolic approach for laparoscopic excision of an extra
      adrenal pheochromocytoma.
AB  - Laparoscopic surgery is an established treatment modality for adrenal disease,
      especially pheochromocytomas. We describe the successful excision of an extra
      adrenal pheochromocytoma using a novel transperitoneal, transmesocolic approach.
      The tumor was located inferior to the left renal hilum in the para-aortic region
      and was found bulging through the descending mesocolon at laparoscopy. The tumor
      was removed without mobilization of the descending colon.

PMID- 16796437
TI  - Laparoscopic end-to-end choledochocholedochostomy for bile duct injury during
      laparoscopic cholecystectomy.
AB  - Bile duct injury is one of the serious complications associated with laparoscopic
      cholecystectomy. If the bile duct injury is circumferential or the bile duct is
      transected, conversion to open surgery is usually done. With the continuing
      development of laparoscopic techniques, procedures that previously seemed
      implausible can now be performed laparoscopically. We describe a case of
      successful laparoscopic end-to-end choledochocholedochostomy after the common
      bile duct was mistaken for the cystic duct intraoperatively and transected.

PMID- 16796438
TI  - Laparoscopic repair of a type II endoleak.
AB  - A 72-year-old male underwent an uncomplicated endovascular repair of a 6.1-cm
      infrarenal abdominal aortic aneurysm. Routine follow-up at 18 months
      postoperatively revealed the presence of a type II endoleak, and that the
      aneurysm had increased in size. The endoleak was repaired by laparoscopic
      ligation of the inferior mesenteric artery. A postoperative computerized
      tomography scan revealed cessation of flow through the inferior mesenteric
      artery. The patient tolerated the procedure well and was discharged home on the
      same day.

PMID- 16796439
TI  - Laparoscopic Nissen fundoplication in a patient with situs inversus totalis: an
      ergonomic consideration.
AB  - We report a laparoscopic Nissen fundoplication for gastroesophageal reflux
      disease in a patient with situs inversus totalis. The 65-year-old man was
      previously diagnosed with situs inversus totalis and presented with chronic
      gastroesophageal reflux disease inadequately controlled by medications. The
      laparoscopic procedure was performed with 5 ports placed in a mirror-image
      configuration and with the patient in the lithotomy position. Few technical
      difficulties were encountered during the operation. The position of the primary
      surgeon, working between the lower limbs of the patient, was considered critical
      to the success of this case. In situs inversus totalis, this position provides
      the least visual disorientation from the reversed abdominal organs. We recommend
      this position for all upper abdominal laparoscopic procedures in patients with
      situs inversus totalis, including laparoscopic cholecystectomy.

PMID- 16796440
TI  - Total laparoscopic right posterior sectionectomy for hepatocellular carcinoma.
AB  - A 57-year-old man presented with a liver mass that had been detected on physical
      examination. The abdominal computed tomography scan revealed a 5-cm single
      nodular hepatoma located in segments 6 and 7. A total laparoscopic right
      posterior sectionectomy was performed for this lesion. The anatomical demarcation
      of the posterior section was possible with selective control of a Glissonian
      pedicle to that section. The patient was discharged on postoperative day 13
      without complications. The postoperative pathology confirmed a hepatocellular
      carcinoma with a 1-cm free resection margin. The patient had no evidence of
      recurrence at 12-month follow-up. To our knowledge, this is the first reported
      case of total laparoscopic right posterior sectionectomy in segments 6 and 7.

PMID- 16796441
TI  - Robot-assisted thoracoscopic esophagectomy with the patient in the prone
      position.
AB  - We describe a new technique of esophagectomy by robot-assisted thoracoscopy with
      the patient in the prone position, followed by laparoscopy and left cervicotomy
      with the patient in the supine position. We report two procedures performed
      November 2002 and September 2003. The technique should allow more thorough lymph
      node removal while reducing postoperative pain and morbidity. The thoracoscopy is
      robot-assisted and the articulations within the pleural cavity improve the
      surgeon's dexterity and reduce trocar movements. The prone position allows
      mobilization of the esophagus with only three trocars because the lung, which is
      partially deflated, does not block access. With the patient in the prone
      position, bleeding does not obscure the operative field. Stomach mobilization,
      gastric tube creation, and celiac lymphadenectomy are performed by laparoscopy.
      The esogastric anastomosis is a totally mechanical side-to-side anastomosis
      realized by left cervicotomy.

PMID- 16796442
TI  - Synchronous laparoscopic sigmoid resection and hysterectomy with transvaginal
      specimen removal.
AB  - INTRODUCTION: Laparoscopic sigmoid resection for recurrent or complicated
      diverticulitis and laparoscopically assisted hysterectomy for leiomyomas of the
      uterus are common procedures. A synchronous combination of these two
      interventions with the advantage of using the vaginal stump as a route for
      removal of the specimen has not previously been described. MATERIALS AND METHODS:
      We used a transvaginal extraction of the uterus and the colorectal segment,
      followed by a totally intra-abdominal circular stapler anastomosis. The procedure
      is performed via four trocar incisions, obviating the need for a laparotomy.
      RESULTS: Two women suffering from diverticulitis and symptomatic uterus
      myomatomas were treated by combined laparoscopic sigmoid resection and
      laparoscopically assisted transvaginal hysterectomy. Both patients had an
      uneventful intraoperative course. DISCUSSION: This new approach, combining two
      operations, is feasible and leads to almost perfect cosmetic results,
      cumulatively shorter hospitalization, and good patient satisfaction. Cooperation
      with a gynecologist as well as experience in advanced laparoscopic surgery is
      essential.

PMID- 16796443
TI  - Retroperitoneoscopy to extract dropped gallstones after laparoscopic
      cholecystectomy.
AB  - Complications resulting from gallstones left in the peritoneal cavity are most
      often reported after laparoscopic treatment of cholelitiasis. Gallstones are
      frequently dropped in the posterior subhepatic space, which can lead to the
      development of abscesses that usually require laparotomy for extraction of the
      stones. We present a novel technique for treating collections associated with
      dropped gallstones, using retroperitoneoscopy with two 10-mm ports after
      ultrasound localization of the abscess. We carried out this procedure in two
      patients and successfully extracted the gallstones without postoperative
      complications or recurrences. We consider this approach to be technically
      feasible, safe, and effective. It avoids the usual inefficacy of simple
      percutaneous drainage of these collections and the complications associated with
      the drainage of intra-abdominal abscesses by laparotomy.

PMID- 16796444
TI  - Diagnosing and treating bleeding portal hypertensive duodenopathy.
AB  - Portal hypertensive duodenopathy is a rare condition related to liver cirrhosis;
      there is little in the literature about its clinical significance and management.
      It seems to be endoscopically and histologically similar to portal hypertensive
      gastropathy, which is well defined. We report the case of a patient, initially
      treated for acute bleeding resulting from the rupture of esophageal varices, who
      developed an atypical endoscopic picture of portal hypertensive duodenopathy over
      a 6-month period. After microscopic definition of the disease we found chronic
      bleeding which required blood transfusions. Medical treatment did not solve the
      problem. We describe an approach using the argon plasma coagulator.

PMID- 16796445
TI  - Endolaparoscopic left hemicolectomy and synchronous laparoscopic radical
      nephrectomy for obstructive carcinoma of the descending colon and renal cell
      carcinoma.
AB  - Colorectal self-expandable metal stents (SEMS) have been used successfully as
      preoperative bridges to surgery for obstructive left-sided colorectal carcinoma.
      Endoscopic relief of the obstruction allows for full bowel preparation and
      accurate preoperative staging. A laparoscopic approach, considered by many to be
      contraindicated in the presence of obstruction, becomes feasible after endoscopic
      decompression. We present a case of obstructive carcinoma of the descending colon
      successfully treated with endoscopic decompression with colorectal SEMS.
      Subsequent staging with computed tomography revealed a renal cell carcinoma in
      the left kidney. Synchronous laparoscopic resection of the two carcinomas was
      performed, with no morbidity. To the best of our knowledge, this is the first
      report of endolaparoscopic left hemicolectomy and synchronous laparoscopic
      radical nephrectomy for obstructive carcinoma of the descending colon and renal
      cell carcinoma. The advantages of colorectal SEMS and the endolaparoscopic
      approach in managing obstructive colorectal carcinoma are discussed.

PMID- 16796446
TI  - A simple technique for laparoscopic removal of silicone adjustable gastric
      banding.
AB  - Laparoscopic adjustable silicone gastric banding is currently among the most
      common surgical procedures performed in morbidly obese patients. The safety,
      reversibility, and technical simplicity of this procedure account for its wide
      and rapid diffusion. Concern still exists about the long term efficacy of the
      procedure in achieving weight loss and mechanical complications continue to
      represent the Achilles' heel of the procedure. Little or no attention has been
      given in the literature to the technical aspects of band removal. The surgical
      technique must be as simple and minimally invasive as possible. We report the
      technique we currently use to remove failed bands.

PMID- 16796447
TI  - Retroperitoneoscopic renal surgery in children: our experience.
AB  - BACKGROUND: Laparoscopic renal surgery has become an accepted approach for benign
      disease in adult and pediatric urology. We present our experience in renal
      laparoscopy in infants during the past 5 years and evaluate our series to
      establish the safety and efficacy of such procedures in children. MATERIALS AND
      METHODS: From August 1999 to December 2004, we performed 32 renal laparoscopic
      procedures on 31 children aged 12 months to 16 years (mean, 42 months). Twenty
      seven patients underwent unilateral retroperitoneal nephrectomy; 1 child with
      Denis Drash syndrome underwent transperitoneal bilateral nephrectomy; 2 children
      underwent renal cyst unroofing; and 1 child with lymphoma underwent
      retroperitoneal laparoscopic renal biopsy. Indications for surgery were: renal
      function <9% in cases of unilateral nephrectomy; the prevention of renal
      neoplastic changes in the patient with Denys-Drash syndrome; symptomatic large
      renal cysts; and suspected lymphoma not diagnosed with a previous percutaneous
      biopsy. RESULTS: All procedures were completed laparoscopically. In 6 cases, the
      accidental opening of the peritoneum did not require conversion to open surgery.
      Intraoperative blood loss was minimal. One patient who underwent a
      retroperitoneal nephrectomy required a blood transfusion for postoperative
      bleeding into the retroperitoneal space. Twenty-four of 27 unilateral
      retroperitoneal nephrectomy patients were discharged on postoperative day 2. Mean
      follow-up was 30 months (range, 6-64 months). Cosmetic results were excellent in
      all patients and no long-term complications have been encountered so far.
      CONCLUSION: Laparoscopic urologic surgery may be performed in children with
      minimal morbidity, minimal postoperative discomfort, improved cosmetic results,
      and a short hospital stay.

PMID- 16796448
TI  - Interval laparoscopic appendectomy in children.
AB  - BACKGROUND: Conservative management of advanced complicated appendicitis in
      children is becoming more common. Formation of an appendiceal mass or abscess may
      mitigate against urgent appendectomy during the acute stage, and conservative
      treatment followed by interval appendectomy has been advocated. We present our
      experience of interval laparoscopic appendectomy in our institution. MATERIALS
      AND METHODS: All children who were offered interval laparoscopic appendectomy
      between January 2000 and December 2004 were included. Retrospective case note
      analysis was performed and data collected included demographics, duration of
      symptoms, method of diagnosis, days of antibiotics, length of interval, operative
      time, length of hospital stay (conservative treatment and interval laparoscopic
      appendectomy), analgesia requirements, complications, and histology. RESULTS:
      Thirty-six children, median age 8 years (range, 1-15 years) diagnosed with
      appendiceal mass or abscess were offered interval laparoscopic appendectomy by
      two surgeons in our institution: one patient declined interval laparoscopic
      appendectomy. Median antibiotic treatment was 10 days (range, 3-23 days). Median
      length of stay for conservative treatment was 6 days (range, 1-27 days). Five
      children required percutaneous drainage. For the 35 children who had interval
      laparoscopic appendectomy, the median interval was 93 days (range, 34-156 days)
      and median operative time was 55 minutes (range, 25-120 minutes). Median length
      of stay for interval laparoscopic appendectomy was 1 day (range, 1-3 days). There
      were no complications following interval laparoscopic appendectomy. CONCLUSION:
      Interval laparoscopic appendectomy can be safely performed in children, is
      associated with a short hospital stay and minimal morbidity, analgesia, and
      scarring following conservative management of appendiceal mass or abscess.
      Interval laparoscopic appendectomy eliminates the risk of recurrent appendicitis
      and serves to excise undiagnosed carcinoid tumors. In future it may be possible
      to perform interval laparoscopic appendectomy as a day-case procedure in selected
      patients.

PMID- 16796449
TI  - Laparoscopic extravesical transperitoneal approach for vesicoureteral reflux.
AB  - INTRODUCTION: Laparoscopy may have a place in the treatment of vesicoureteral
      reflux. In this study, we present the results of laparoscopic extravesical
      transperitoneal treatment in 15 children (19 ureters) of vesicoureteral reflux.
      MATERIALS AND METHODS: Between January 2001 and February 2004, 15 children (11
      with unilateral and 4 with bilateral vesicoureteral reflux) were treated with
      extravesical reimplantation (Lich- Gregoir technique) via a transperitoneal
      laparoscopic approach. The mean age was 48.2 months (range 12-62), and there were
      14 females and 1 male. Two patients had a double total collector system
      associated with reflux without ureterocele. RESULTS: The mean surgical time was
      110 minutes in unilateral and 180 in bilateral vesicoureteral reflux. All
      procedures were successfully completed laparoscopically and the reflux was
      corrected in all but one patient, whose grade III vesicoureteral reflux changed
      to grade I. We had 3 mucosal perforations without leakage. The longest hospital
      stay was 72 hours. After follow-up ranging 15-49 months, only one patient had
      urinary tract infection. CONCLUSION: Laparoscopic extravesical transperitoneal
      reimplantation for vesicoureteral reflux is a safe and effective approach even in
      bilateral simultaneous and duplex ureters, with success rates similar to the open
      technique, and a dramatic reduction in postoperative stay. Mucosal perforation
      was treated by maintaining a Foley catheter for 3-4 days postoperatively.

PMID- 16796450
TI  - A novel treatment of congenital duodenal stenosis: image-guided treatment of
      congenital and acquired bowel strictures in children.
AB  - BACKGROUND: Image-guided balloon dilatation has been used in adults as an
      alternative to standard surgical treatment of intestinal stricture. The
      experience in children is limited. We report our results with this procedure in
      the management of both congenital and acquired intestinal stenosis in children.
      MATERIALS AND METHODS: A retrospective analysis was done of children younger than
      2 years of age who underwent balloon dilatation of small and large intestinal
      stenosis between 1994 and 2003. RESULTS: Eleven children underwent dilatation
      during the study period. Two of these children had congenital duodenal stenosis,
      and this represents the first report of nonoperative management of this
      condition. Three children underwent dilatation of small bowel strictures and 6
      had dilatation of colonic and rectal strictures. Necrotizing enterocolitis was
      the most common (6/9) etiology of stricture. Ten of 11 patients did not require
      subsequent operative management although 3 children required further dilatations.
      The mean follow-up was 36.5 months (range, 13 days-103 months). One patient
      underwent a subsequent dilatation that was unsuccessful, and required operative
      resection of a 5-cm stricture. There was one complication, a small leak that was
      managed nonoperatively. CONCLUSION: Image-guided balloon dilatation holds promise
      as an alternative to surgical treatment in children with congenital or acquired
      stenosis of the small or large bowel, and should be considered in select patients
      with short strictures.

PMID- 16796451
TI  - Laparoscopic orchiopexy for palpable undescended testes: a five-year experience.
AB  - BACKGROUND: Most recent reports of laparoscopic orchiopexy concern nonpalpable
      testes. We report the results of this approach in patients with undescended
      palpable testes. MATERIALS AND METHODS: Between January 1999 and September 2004,
      28 patients with 30 undescended palpable testes were treated by laparoscopic
      orchiopexy performed by the same surgeon. Patients with palpable cryptorchidism
      were included. Patients with nonpalpable testes, retractable, or vanishing testes
      were excluded. The mean age of the patients was 25 months (range, 8 months-5
      years) and the mean weight was 16 kg (range, 8-24 kg). We used a 4-port technique
      (one 10-mm, two 2-3 mm, and one 5-mm), a 4-mm scope, and 2-3 mm instruments.
      RESULTS: The mean operative time was 50 minutes. The complication rate was 13.3%
      (4/28), all in the first two years, at the beginning of the learning curve. The
      remaining testes were descended by laparoscopy; 5 (16.6%) were peeping testes. We
      had 10 (33.3%) left and 16 (53.3%) right palpable cryptorchidia cases, plus 4
      testes (13.3%) that were bilateral undescended and palpable. No hernia was found
      in 8 (28.6%) cases; a homolateral hernia was found in 18 (64.3%) cases, and we
      did not close the processus vaginalis, we only resected the membranes. We found 2
      (7.1%) with contralateral hernia in which we did close the processus vaginalis.
      On follow-up ranging 5 months-5 years, 29 of these testes maintain good size and
      a correct position, with no recurrent inguinal hernia. CONCLUSION: The
      laparoscopic approach is a safe way to descend the palpable testicle. Although
      this is not a large series, it shows that laparoscopic orchiopexy of palpable
      undescended testes can be done without a higher complication rate than the open
      procedure (13.3% vs. 12.2%), with several of the advantages of the laparoscopic
      approach.

PMID- 16796452
TI  - Atypical laparoscopic resection of a liver tumor in a 4-year-old girl.
AB  - Despite the advances in minimally invasive surgery in children, considerable
      concern exists about employing such techniques in oncologic cases. We report our
      experience with a 4-year-old girl with a symptomatic tumor in the liver. Contrast
      enhanced computed tomography revealed a 3 x 4 cm lesion, confined to segments II
      and III. Tumor markers were negative and true-cut needle biopsy did not rule out
      malignancy. We performed a diagnostic laparoscopy using four 5-mm ports. Since
      the tumor did not cause any alterations of the liver surface, a 5-mm flexible
      endoscopic ultrasound probe (5 MHz) was applied to reveal the extent of the
      tumor. Parenchymal dissection was performed with a radiofrequency probe, and the
      LigaSure device was used to seal larger vessels and bile ducts. The tumor was
      resected completely and removed in a specimen bag via the umbilical incision.
      Histology revealed fibrous nodular hyperplasia. The postoperative course was
      uneventful and the girl was discharged on postoperative day 5. We conclude that
      laparoscopic resection of confined liver lesions is feasible in children,
      employing standard principles of oncologic surgery and safety.

PMID- 16796453
TI  - Pediatric wandering spleen successfully treated by laparoscopic splenopexy.
AB  - Wandering spleen is a rare clinical condition associated with a high incidence of
      splenic torsion and infarction. The preferred treatment is splenopexy to
      reposition the spleen in the left upper quadrant of the abdomen. We report the
      case of a 12-year-old girl who presented with intermittent abdominal pain. An
      abdominal sonography was diagnostic of wandering spleen. The patient was
      successfully treated by laparoscopic splenopexy. The spleen was repositioned in
      the left upper quadrant and fixed to the posterior abdominal wall by a mesh patch
      attached by staples. To reinforce the splenopexy we created an additional support
      by plicating the phrenocolic ligament and suturing it to the lateral abdominal
      wall, making a pouch for the inferior pole of the spleen. The postoperative
      course was rapid and uneventful. A normal spleen position was verified by
      radionuclide scans at 3 days and 6 months postoperatively. Laparoscopic
      splenopexy is an excellent option for organ-preserving treatment in wandering
      spleen.

PMID- 16796454
TI  - Laparoscopic resection of esophageal stricture with transgastric stapled
      anastomosis in a child with AIDS.
AB  - A tight stricture in the lower esophageal stricture in a child poses significant
      surgical challenges. We report the first case of a laparoscopically assisted
      resection of a distal esophageal stricture in a 2-year-old girl with clinical
      AIDS (CDC stage 3). The patient presented with dysphagia, vomiting, and
      progressive weight loss. A barium swallow confirmed a distal tight esophageal
      stricture in the lower esophagus. After the second dilatation attempt failed a
      gastrostomy was inserted and highly active antiretroviral therapy treatment
      commenced. Follow-up contrast studies showed a nearly complete obstruction of the
      distal esophagus. A laparoscopically assisted resection of the esophageal
      stricture with a primary stapled anastomosis was performed with good results. At
      follow-up 8 months postoperative the child was tolerating feeds well and
      thriving.

PMID- 16796455
TI  - Laparoscopic management of insulinoma in a child with multiple endocrine
      neoplasia type 1.
AB  - The diagnosis and surgical management of insulinomas associated with multiple
      endocrine neoplasia type 1 (MEN1) pose additional problems in children because of
      the long-term risk of recurrence of other pancreatic and non-pancreatic tumors.
      We report a diagnostic confirmation by laparoscopic ultrasound of an insulinoma
      and its successful removal by laparoscopic enucleation in an 8- year-old boy who
      was admitted to our hospital with a history of recurrent episodes of absences,
      headache, and visual and auditive disturbances diagnosed as hyperinsulinism
      related hypoglycemia. Magnetic resonance imaging of the pancreas showed a small
      contrast-enhancing lesion in the body of the pancreas, suspected for insulinoma.
      MEN1 was genetically proven by direct DNA testing. A pancreatic tumor can arise
      before the age of 10 in patients with MEN1 and can be surgically treated by a
      laparoscopical approach.

PMID- 16796456
TI  - A unique CD72 epitope suggests a potential interaction with Fc gamma RII/CD32 on
      B lineage lymphocytes.
AB  - It has long been known that ligation of the transmembrane CD72 glycoprotein
      delivers signals to B lymphocytes, with the outcome depending on context. Of
      particular interest is its ability to function as a counter-receptor/ ligand for
      the CD100 semaphorin protein. We have now obtained evidence that CD72 physically
      interacts on the lymphocyte membrane with Fcgamma receptor II (CD32). The
      association was first revealed with a new monoclonal antibody that recognizes
      polymorphic determinants on murine CD72. Although the specificity for CD72 was
      clear from immunoblotting, transfection and other experiments, staining with this
      reagent was inhibited when cells were pretreated with an Fc receptor-blocking
      antibody (CD16/CD32 specific). Furthermore, confocal microscopy revealed that the
      two molecules co-distributed on viable B cells. We also used the antibody to
      determine when CD72 becomes available to maturing lymphocytes. The marker is
      first acquired as large pre-B cells and enter the IL-7 independent phase of
      maturation within bone marrow. Subsequent interactions between CD72 and CD32 may
      cooperatively deliver negative signals that modulate humoral immune responses.

PMID- 16796457
TI  - Generation and characterization of monoclonal antibodies to human keratinocyte
      growth factor receptor.
AB  - Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor
      (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain
      in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have
      not been reported nor are commercially available. In this study, we generated
      murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified
      Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines
      expressing the full-length human KGFR or FGFR2c were produced to facilitate the
      identification of KGFR-specific MAbs. Following the initial screening of
      hybridoma clones with a fluorescence-based, confocal cell detection method and
      ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and
      Western blot analyses. Antagonistic MAbs were identified using a cell-based
      functional assay. These KGFR MAbs will be important reagents for studying the
      biological function and tissue distribution of this receptor in normal and
      pathological conditions.

PMID- 16796458
TI  - Use of monoclonal anti-EGFR antibody in the radioimmunotherapy of malignant
      gliomas in the context of EGFR expression in grade III and IV tumors.
AB  - We investigated the putative benefits of simultaneous teleradiotherapy and anti
      epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425
      radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over
      teleradiotherapy alone. In comparison to previous studies which have reported
      good results with this type of radioimmunotherapy, we advanced the adjuvant
      radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy.
      The randomized prospective study examined two groups: simultaneous postoperative
      teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus
      teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation
      of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of
      remnant tumor on post-operative magnetic resonance (MR) study and were not
      treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR
      125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks
      after neurosurgery, and was repeated three times at 1-week intervals. Total
      activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No
      immediate side effects of concomitant anti-EGRF 125I RIT were observed.
      Observation showed a median total survival (as evaluated from the primary
      neurosurgical treatment) of 14 months (range 3.5-28 months). There was no
      improvement in disease-free or total survival in the group of patients treated by
      TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of
      EGFR expression in gliomas was performed in a group of 100 cases and was
      distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We
      conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR
      125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of
      high-grade gliomas after neurosurgery. We also recommend individual confirmation
      of EGFR expression in further anti-EGFR radioimmunotherapy trials.

PMID- 16796459
TI  - Structural mapping of immunoglobulin subclasses using multiplexed bead flow
      cytometry.
AB  - Monoclonal hybridomas secrete immunoglobulin molecules with a single specificity
      and distinct class/subclass structure. The determination of immunoglobulin
      structure can be used to facilitate hybridoma colony management and predict
      monoclonality. In this report, we used multiplexed bead flow cytometry to define
      hybridoma class/subclass. The assay was sufficiently sensitive to detect 50 ng/mL
      of antibody. The multiplexed bead assay efficiently defined traditional
      class/subclass determinants as well as more subtle patterns of crossreactivity.
      Further, the assay was combined with Poisson statistics to provide a numerical
      estimate of hybridoma monoclonality. The sensitivity and flexibility of this
      approach suggests the utility of multiplexed bead flow cytometry in the early
      management of immunoglobulin-secreting hybridomas.

PMID- 16796460
TI  - Derivation and characterization of a monoclonal antibody against human
      glycinamide ribonucleotide formyltransferase.
AB  - Glycinamide ribonucleotide formyltransferase (GARFT) is a trifunctional enzyme
      involved in purine biosynthesis. Its central role in folate metabolism has made
      it an obvious target for the development of GARFT inhibitors, primarily for
      oncology. While the crystal structure, enzyme kinetics, and mechanism of action
      of GARFT inhibitors are reasonably well understood, GARFT regulation at the
      protein level remains unclear. The present study reports the development and
      characterization of a monoclonal antibody (MAb) specific for human GARFT. This
      MAb, an IgG1kappa, designated PHR1, recognizes human GARFT by both Western blot
      and by immunohistochemistry from non-small-cell lung carcinoma and colon
      adenocarcinoma tissue biopsies, has a KD of 1.14 x 10(10) M, and has been epitope
      mapped at residues 59-78 of the GARFT functional domain. The ability of PHR1 to
      recognize both sodium dodecyl sulfate (SDS)-denatured as well as native GARFT
      should make this MAb an important research tool in determining GARFT protein
      levels in both normal and neoplastic tissues.

PMID- 16796461
TI  - Effect of antibody to CD134 on perforin-mediated cytolysis in human peripheral
      blood mononuclear cells.
AB  - CD134 (OX40) is a new member of the tumor necrosis factor receptor (TNFR)
      superfamily. The influence of CD134 on perforin-mediated cytolysis remains
      obscure. In this study, human peripheral blood mononuclear cells (PBMC) were
      induced with phytohemagglutinin (50 microg/mL), by using anti-CD134 blocking
      monoclonal antibody (MAb; 1, 5, and 10 microg/mL) for 6, 12, 24, and 48 h.
      Perforin-mediated cytolysis against human erythrocytes of PBMC was detected. The
      expression of perforin mRNA and protein was also measured by reverse
      transcription-polymerase chain reaction and flow cytometry. Our data showed that
      the perforin-mediated cytolysis of PBMC was downregulated by various
      concentrations of anti-CD134 blocking MAb for different times and reached a
      minimum at 24 h at any concentration. Anti-CD134 blocking MAb induced
      downregulation of perforin-mediated cytolysis of PBMC in a dose-dependent manner
      in the range of 1-5 microg/mL. Perforin- mediated cytolysis of PBMC reached a
      plateau when the concentration of anti-CD134 blocking MAb exceeded 5 microg/mL.
      Anti-CD134 blocking MAb also induced the inhibition of the expression of perforin
      protein and mRNA in PBMC. In conclusion, anti-CD134 blocking MAb inhibits
      perforin-mediated cytolysis of PBMC by, at least in some part, decreasing the
      production of preforin, which may be useful in treating several autoimmune
      diseases.

PMID- 16796462
TI  - Monoclonal antibody FsC-47 against carp sperm creatine kinase.
AB  - The enzyme creatine kinase (CK) plays a key role in energy homeostasis of cells
      with high and fluctuating energy requirements. As for spermatozoa, the activity
      of phosphocreatine shuttle, which directs energy from the mitochondria to sites
      of ATP consumption, is dependent on individual species. High activities of CK are
      observed in spermatozoa of nonvertebrate, fish, and birds, contrary to the low
      level CK activity in mammalian spermatozoa. A new monoclonal antibody (MAb) to
      carp sperm creatine kinase was prepared. This antibody is applicable to large
      scale immunochemical techniques. In this study, it was applied to the study of
      carp sperm motility, and the evaluation of the influence of CK on the quality and
      fertilization ability of carp spermatozoa.

PMID- 16796463
TI  - Generation and characterization of monoclonal antibodies against the
      intracellular domain of hemidesmosomal type XVII collagen.
AB  - Type XVII collagen, also referred to as bullous pemphigoid antigen 2 (BPAG2) or
      bullous pemphigoid antigen 180 (BP180), is a transmembrane protein of the
      hemidesmosomal complexes of keratinocytes. Type XVII collagen has an unusual type
      II orientation with its N-terminus intracellularly located and with a large
      extracellular domain that spans lamina lucida of the dermal-epidermal junction.
      Type XVII collagen is an autoantigen in patients with pemphigoid diseases and its
      gene is mutated in patients with junctional epidermolysis bullosa. In the present
      work, we generated new monoclonal antibodies (MAbs) against the intracellular
      domain of type XVII collagen. We further characterized reactivity and fine
      specificity of an MAb (clone V58) from this panel of antibodies. The epitope
      recognized by the mAb V58 was mapped to a stretch of type XVII collagen
      corresponding to residues 234-398 of its sequence. Possible applications of this
      new MAb include antigen mapping in patients with hereditary epidermolysis bullosa
      and immunoaffinity purification of cell-derived type XVII collagen.

PMID- 16796474
TI  - Improving women's health for the sake of our children.
AB  - Improving the health of our children offers the greatest potential for improving
      the health of our nation. One paradigm for improving the health of children that
      may offer the greatest rate of return lies in improving the health of women.
      Throughout the complete life stages of both women and children, overall good
      health of women positively influences the health and wellness of our children.

PMID- 16796475
TI  - Toward optimal health: JudyAnn Bigby, M.D., discusses the need for cultural
      competence in the healthcare of women. Interview by Jodi R. Godfrey.

PMID- 16796476
TI  - Global understanding of barriers to breast cancer screening.

PMID- 16796477
TI  - Predictors of breast cancer screening among immigrant Iranian women in
      California.
AB  - OBJECTIVE: This study examined the predictors of age-specific breast cancer
      screening participation among immigrant Iranian women aged 30 years and older.
      METHODS: Logistic regression was used to identify predictors of women's breast
      cancer screening. The logistic regression results appear as odds ratios (ORs) and
      95% confidence intervals (CIs). RESULTS: In general, screening rates for clinical
      breast examinations (CBE) and mammography among the participants in the current
      study were higher than levels set in the year 2010 Health Objectives and those
      reported for women nationally. These findings are inconsistent with previous
      studies on immigrant women living in the United States. However, the low rate of
      breast self-examinations (BSE) is consistent with previous findings of other
      immigrant women breast cancer screening studies. CONCLUSIONS: This study is the
      first of its kind to explore predictors of Iranian immigrant women's breast
      cancer screening behaviors. This study provides valuable information to
      healthcare providers as well as researchers and public health educators. The
      findings can make a significant difference in designing guidelines for culturally
      sensitive interventions and educational material to improve breast cancer
      screening behaviors.

PMID- 16796478
TI  - Breast cancer early detection among Chinese women in the Philadelphia area.
AB  - BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the second
      leading cause of cancer death among Chinese American women. Previous studies
      identified disparities in breast cancer screening between Asian and Caucasian
      women. This study describes breast cancer awareness, attitudes, and knowledge, as
      well as barriers and facilitators of early detection among Chinese women in
      Philadelphia. METHODS: A cross-sectional, translated survey was conducted among a
      convenience sample of 111 Chinese women from the greater Philadelphia area. Data
      were analyzed using descriptive statistics to describe participant experiences
      and attitudes, and Pearson correlation coefficients, chi-square tests, and
      multiple regressions were used to identify significant predictors of breast
      cancer screenings. RESULTS: Of respondents, 53.2% had ever performed breast self
      examination (BSE). Among women aged >or=40, 53.6% had ever had clinical breast
      examination (CBE), and 71.1% had ever had mammogram. Knowledge (p < 0.001) and
      self-efficacy (p = 0.001) predicted BSE ever performance. Having a doctor as
      information source of CBE (p = 0.001) and belief in family history as a risk
      factor of breast cancer (p = 0.002) were significant predictors of having ever
      had a CBE. Having a doctor as information source of mammogram (p = 0.002) was the
      only significant predictor of having ever had mammogram screening. CONCLUSIONS:
      This study laid a foundation for developing culturally sensitive breast cancer
      education and screening programs for Chinese women in the Philadelphia area.
      Recommendations include a call for physician education to improve breast cancer
      screening rates in this population.

PMID- 16796479
TI  - Health beliefs and rates of breast cancer screening among Arab women.
AB  - OBJECTIVES: To examine the relationship between health beliefs and participation
      in breast cancer screening among Arab women in Israel. METHODS: A random sample
      of 568 Arab women, aged 20-60, belonging to three religious groups, Muslim,
      Christian, and Druze, was recruited. Participants answered a telephone
      questionnaire regarding attendance for mammography screening and clinical breast
      examination (CBE) and health beliefs. RESULTS: Christian women had undergone more
      mammography screening and CBE than Druze and Muslim women. They perceived more
      benefits and fewer barriers to screening practices and had greater perception of
      the severity of breast cancer. Perception of susceptibility was similar across
      groups. The barriers that were significant for the Druze and Muslim women were
      feelings of discomfort and embarrassment, the belief that there was no cure in
      the case of a positive finding, perceiving mammography as hazardous to health,
      and perceiving CBE as painful. Logistic regression revealed that age, group, and
      having a first-degree relative with breast cancer predicted participation in
      early detection screening. Physician's recommendation predicted mammography, and
      level of participants' religiosity predicted CBE. CONCLUSIONS: Diversity in
      health beliefs and behaviors exists in religious subgroups. Health communications
      should be modified to suit women in different groups in order to increase
      participation in screening. In addition, physicians have to be made keenly aware
      of their pivotal role in motivating women to participate in early detection
      screening.

PMID- 16796480
TI  - Breast and cervical cancer screening in obese minority women.
AB  - PURPOSE: Studies using survey data from mostly white women showed that obese
      women are less likely than nonobese women to undergo breast and cervical cancer
      screening. It is unclear if these findings are true in nonwhite women. Using
      chart audit data, we examined the relationship between obesity and mammography
      and Pap smear screening among minority women. METHODS: Data from retrospective
      chart review of women in three urban New Jersey academic family medicine
      practices were analyzed (n = 1809) using hierarchical logistic regression models.
      Outcome measures were being up-to-date in mammography and Pap smears among obese
      and nonobese women. RESULTS: There was no difference in mammography rates among
      obese and nonobese women. Independent risk factors for not being up-to-date in
      mammography included age 40-49, smoking, and comorbidity. Obese women were less
      likely than nonobese women to be upto- date in Pap smears (69% vs. 77%, p =
      0.001). In multivariate analysis, obesity was associated with 25% decreased odds
      of being up-to-date on Pap smears (OR, 0.75, 95% CI, 0.58-0.99, p = 0.041). Age
      >or=65 years was also associated with decreased odds of being up-to-date in Pap
      smears. Hispanic women had increased odds of being up-to-date in mammography (OR
      2.43, 95% CI 1.63-3.63) and Pap smears (OR 1.94, 95% CI 1.24-3.03) compared with
      white women. CONCLUSIONS: Obesity was associated with decreased Pap smear
      screening but not with decreased mammography. Further studies are needed to
      determine barriers and effective interventions to improve screening in obese
      minority women.

PMID- 16796481
TI  - Performance of breast cancer early detection in arab women in Israel--room for
      improvement.

PMID- 16796482
TI  - Evaluating the criteria used for identification of PMS.
AB  - OBJECTIVE: Criteria for defining premenstrual syndrome (PMS) were assessed by
      comparing a reference definition previously demonstrated to be associated with
      reduced health-related quality of life and impaired productivity with alternative
      definitions based on criteria stringency variations. METHODS: Health-related
      quality of life data were collected from the Medical Outcomes Study Short Form-36
      (SF-36) for women aged 18-64 years. Women maintained daily calendars of emotional
      and physical symptoms and work productivity. PMS prevalence and differences in
      health-related quality of life and work productivity between women with and
      without PMS were compared using alternative definitions. RESULTS: Across
      criteria, PMS prevalence ranged from 19% to 30%. Regardless of the criteria used,
      PMS was associated with reductions in health-related quality of life, with Mental
      Components Subscale scores 5-12 points lower for women with PMS compared to those
      without PMS. Likewise, across definitions, women with PMS had greater work
      productivity impairment than women without PMS, netting 4 additional days with
      reduced productivity per month. CONCLUSIONS: PMS prevalence varies based on
      criteria used to define illness. However, PMS is associated with reductions in
      health-related quality of life and work productivity impairment regardless of the
      criteria used.

PMID- 16796485
TI  - A review of drospirenone for safety and tolerability and effects on endometrial
      safety and lipid parameters contrasted with medroxyprogesterone acetate,
      levonorgestrel, and micronized progesterone.
AB  - BACKGROUND: Drospirenone, a novel synthetic progestin, possesses characteristics
      more like natural progesterone than other synthetic progestins, such as
      medroxyprogesterone acetate and levonorgestrel. The antiandrogenic and
      antimineralocorticoid properties of drospirenone may, in the context of
      menopausal management, provide potential novel benefits in its effect on lipids
      and blood pressure while reducing the occurrence of water retention, acne
      vulgaris, and hirsutism. METHODS: This review compares safety and tolerability
      data from clinical trials of drospirenone, medroxyprogesterone acetate,
      levonorgestrel, and micronized progesterone. RESULTS: Results suggest that
      drospirenone possesses a generally well-accepted side effect profile and
      resembles comparator oral progestogens in conferring endometrial protection with
      no significant effect on weight. One study indicates that drospirenone may have a
      benign effect on lipid parameters, having been seen to significantly lower total
      cholesterol and lowdensity lipoprotein levels while maintaining high-density
      lipoprotein and triglyceride levels. Drospirenone also differs from the other
      progestogens in lowering blood pressure levels in hypertensive patients while
      having a mild blood pressure-lowering effect on nonhypertensive patients.
      CONCLUSIONS: Among pharmacological options for menopause management, drospirenone
      may provide certain advantages over other progestogens in its effect on risk
      factors for cardiovascular disease and, thus, constitutes a useful addition to
      the menopausal armamentarium.

PMID- 16796484
TI  - Linking clinical care to community resources for cardiovascular disease
      prevention: the North Carolina Enhanced WISEWOMAN project.
AB  - BACKGROUND: The Well-Integrated Screening and Evaluation for Women Across the
      Nation (WISEWOMAN) project addresses the need for effective cardiovascular
      disease (CVD) prevention among underserved, midlife women. We describe an
      Enhanced Intervention that addressed environmental and individual factors within
      the context of a clinic-based intervention. We also present the study design and
      baseline results of the randomized trial to evaluate the enhanced intervention.
      METHODS: The multicomponent behavior change intervention addressed many elements
      of the Chronic Care Model (CCM), including the community resources and policy
      element, wherein Enhanced Intervention participants were encouraged to overcome
      environmental barriers to a healthy lifestyle by using community resources. Study
      participants were enrolled at one community health center; all were low-income,
      underinsured, midlife (40-64 years) women. RESULTS: A total of 236 participants
      were randomized to receive the Enhanced Intervention or the Minimum Intervention.
      At baseline, over three fourths of the participants were overweight or obese.
      Participants reported a variety of problematic neighborhood characteristics,
      including a paucity of restaurants with healthy food choices (41% reported as a
      problem); not enough farmer's markets or produce stands (50%), not enough
      affordable exercise places (52%), not enough physical activity programs that met
      women's needs (42%), heavy traffic (47%), and speeding drivers (53%). Overall,
      women knew little about affordable exercise venues and nutrition classes.
      CONCLUSIONS: In this clinic-based intervention, we addressed environmental
      factors related to a healthy lifestyle. Results indicate the need for effective
      and feasible intervention strategies to address the environments in which
      individuals are making behavior changes. The effectiveness of the WISEWOMAN
      Enhanced Intervention will be assessed in a randomized trial.

PMID- 16796483
TI  - Drug use, drug severity, and help-seeking behaviors of lesbian and bisexual
      women.
AB  - BACKGROUND: Illicit substance use and abuse may be an important contributor to
      behavioral health problems of lesbian and bisexual women. This paper describes
      the nature and extent of self-reported illicit and licit drug use, associated
      severity, and substance use-related helpseeking behaviors in an
      urban/metropolitan community sample of sexual minority women in California.
      METHODS: Self-administered questionnaire data from 2011 lesbian and bisexual
      women recruited through multiple strategies were used. Multiple logistic
      regression was employed to describe patterns of reported drug use and to compare
      lifetime severity of drug use with demographic characteristics, recent drug use,
      indicators of current social and emotional problems, and help-seeking behaviors.
      RESULTS: Drug use, especially marijuana (33% used in the past year), was fairly
      common. Overall, 16.2% of the women in the study reported lifetime drug use that
      was associated with self-reported severity of substance use, and another 10.8%
      indicated moderate-risk use. Extent of lifetime drug use was positively
      correlated with self-reported recent drug use as well as current life problems.
      Of the respondents who evidenced more problematic drug use, 41.5% indicated that
      they had received professional help for a substance use problem, and 16.3% wanted
      but had not received such help. CONCLUSIONS: The women in this study reported
      elevated rates of illicit drug use that was frequently associated with impairment
      and specific life problems. A significant proportion wanted and had not received
      professional treatment for their drug use problems. Future studies that examine
      pathways by which lesbians and bisexual women can obtain referrals and treatment
      for substance use problems are needed.

PMID- 16796486
TI  - Effects of HIV infection and its treatment on self-reported menstrual
      abnormalities in women.
AB  - OBJECTIVE: To describe menstrual abnormalities among women with HIV. METHODS:
      Women in a multicenter prospective cohort study of HIV natural history reported
      menstrual abnormalities every 6-months between October 1994 and September 2002.
      Logistic regression and Cox proportional-hazards models were applied. RESULTS:
      The prevalence and incidence of menstrual abnormalities were <20%. HIV serostatus
      was not associated with prevalent menstrual abnormalities, but in HIV
      seropositive women, higher CD4 counts were associated with fewer problems:
      compared with women with CD4 counts <200/mm3, in women with counts 200-500/mm3,
      odds ratio (OR) for amenorrhea was 0.55, p = 0.02, and for oligomenorrhea was
      0.54, p = 0.0003; for women with counts >500/mm3, OR for amenorrhea was 0.67, p =
      0.14, and for oligomenorrhea was 0.55, p = 0.001. HIV serostatus was not
      associated with incident abnormalities. Highly active anti-retroviral therapy
      (HAART) use was not associated with prevalent abnormalities, but both HAART use
      and higher CD4 counts were linked to lower rates of incident menstrual problems.
      CONCLUSIONS: Compared with seronegative women, HIV-seropositive women are at
      increased risk for some menstrual changes, although the absolute frequency of
      most abnormalities is low. Higher CD4 counts and HAART protect against incident
      abnormalities.

PMID- 16796487
TI  - The impact of physical, psychological, and sexual intimate male partner violence
      on women's mental health: depressive symptoms, posttraumatic stress disorder,
      state anxiety, and suicide.
AB  - OBJECTIVE: This study aimed to determine the impact of lifetime physical,
      psychological, and sexual intimate male partner violence (IPV) on the mental
      health of women, after controlling for the contribution of lifetime
      victimization. The comorbidity of depressive symptoms and posttraumatic stress
      disorder (PTSD) and their relation to state anxiety and suicide were also
      assessed. METHODS: Physically/psychologically (n = 75) and psychologically abused
      women (n = 55) were compared with nonabused control women (n = 52). Information
      about sociodemographic characteristics, lifetime victimization, and mental health
      status (depressive and state anxiety symptoms, PTSD, and suicide) was obtained
      through face-to-face structured interviews. RESULTS: Women exposed to
      physical/psychological and psychological IPV had a higher incidence and severity
      of depressive and anxiety symptoms, PTSD, and thoughts of suicide than control
      women, with no differences between the two abused groups. The concomitance of
      sexual violence was associated with a higher severity of depressive symptoms in
      both abused groups and a higher incidence of suicide attempts in the
      physically/psychologically abused group. The incidence of PTSD alone was very
      rare, and depressive symptoms were either alone or comorbid with PTSD. The
      severity of state anxiety was higher in abused women with depressive symptoms or
      comorbidity, as was the incidence of suicidal thoughts in the
      physically/psychologically abused group. Lifetime victimization was not a
      predictor of the deterioration of mental health in this study. CONCLUSIONS: These
      findings indicate that psychological IPV is as detrimental as physical IPV, with
      the exception of effects on suicidality, which emphasizes that psychological IPV
      should be considered a major type of violence by all professionals involved.

PMID- 16796493
TI  - Are you a telemedicine evangelist?

PMID- 16796495
TI  - Telethinking; with Robert J. Waters, J.D. Interview by Vicki Glaser.

PMID- 16796496
TI  - Telehealth services to improve nonadherence: A placebo-controlled study.
AB  - The objective of this study was to test whether a telehealth intervention could
      improve the compliance with continuous positive airway pressure (CPAP) by
      patients with sleep apnea. These patients had been nonadherent for the initial 3
      months of therapy even after receiving the initial standard and then supplemental
      audiotaped/videotaped patient education for adhering to CPAP nightly. The
      materials and methods included a randomized testing of experimental and placebo
      interventions. Interventions were delivered by nurses to two groups in their
      homes by telehealth over a 12-week period. The placebo intervention was used to
      control for Hawthorne effect, time and attention influences and the novelty of
      having telehealth in the home. Results following the telehealth interventions
      were that significantly more patients in the experimental group 1 (n = 10) than
      the placebo group 2 (n = 9) were adhering nightly to CPAP (chi 2 = 4.55, p =
      0.033). Group 1 patients reported greater satisfaction with their intervention.
      However, both groups rated telehealth delivery positively. The mean cost of each
      20-minute telehealth visit was 30 dollars while the total cost of the telehealth
      intervention for each patient was 420 dollars. These costs included telehealth
      equipment, initial installation, longdistance telephone charges, nurse salary,
      and intervention materials. Conclusions are that telehealth interventions are a
      potentially cost-effective service for increasing adherence to prescribed medical
      treatments. Replication studies with large samples and in other clinical groups
      are recommended.

PMID- 16796497
TI  - Outcomes associated with a home care telehealth intervention.
AB  - To determine whether adding telehealth technology to traditional home care
      services increases health-related quality of life (HRQOL) and home care
      satisfaction, and decreases resource utilization among home care patients. This
      trial included 37 home care patients receiving services in a Veterans Affairs
      medical center, randomized into intervention and control groups. Outcome measures
      included patient satisfaction and HRQOL at baseline and 6-month follow- up, and
      the use of inpatient and outpatient services before and during the 6-month study
      period. Intervention group patients reported greater improvement in the mental
      health component of HRQOL, (t = 2.27; df = 15; p = 0.04). Satisfaction with the
      telehealth equipment was high (means exceeded 4.0 on six measures ranging from 1
      5). However, no statistically significant differences were observed between
      intervention and control groups in terms of changes in physical health, inpatient
      admissions, bed days of care, emergency department visits, or general
      satisfaction with home care services. Intervention group members did show a trend
      (p = 0.10) toward fewer overall outpatient visits (mean = 29.1; standard
      deviation [SD] +/- 30.1) compared to those receiving traditional home care
      services (mean = 38.9; SD +/- 28.9) The use of telehealth services as an adjunct
      to traditional home care is associated with greater improvements in mental health
      status and a trend toward lower use of inpatient and outpatient healthcare
      services. Further work, utilizing larger sample sizes, is needed to investigate
      the relationship between telehealth services, the use of healthcare resources,
      and other outcomes.

PMID- 16796498
TI  - Effectiveness of telemedicine in replacing in-person evaluation for acute
      childhood illness in office settings.
AB  - For the purpose of reducing the social and economic burden imposed by common
      acute childhood illness, we developed a telemedicine model to enable diagnosis
      and treatment of illness episodes presenting in pediatric office settings. The
      study objective was to assess the effectiveness of this telemedicine model in
      replacing illness visits to traditional healthcare settings and to compare
      effectiveness of this model (base model) with that of alternative models
      including simple office laboratory tests and albuterol administration (simple
      model) or a complete complement of tests and procedures (extended model).
      Eligible subjects had an acute problem and were seen in the pediatric primary
      care practice or pediatric emergency department of the University of Rochester
      Medical Center. All subjects were seen by the setting's usual physician. Subjects
      were also evaluated, based on random assignment, by a study physician in person
      or by a study physician via telemedicine. Effectiveness was defined as completion
      of the visit to the point that diagnosis was made. Forms completed by study
      physicians, and standard medical records indicating the tests and procedures
      requested for the purpose of completing the visit, were used to identify the
      model used in completing the visit. Effectiveness (proportion of visits
      completed) of the base model was assessed and its effectiveness was compared to
      that of simple and extended telemedicine models. Among 520 randomized visits, 492
      were evaluated by study physicians in person (253) or via telemedicine (239).
      Using the base model, study physicians completed 74.1% of visits via telemedicine
      compared to 76.7% for study physicians in person and 76.0% for usual physicians.
      The simple model increased completion rates substantially. Using this model,
      study physicians completed 84.9% of visits via telemedicine compared to 86.6% for
      study physicians in person and 85.2% for usual physicians. The extended model
      increased effectiveness in completing visits still more, with telemedicine study
      physicians completing 97.1% of visits compared to 96.8% for in-person study
      physicians and 100% for usual physicians. Approximately 85% of illness visits
      presenting to primary care pediatric practice could be completed using a
      telemedicine model that included only simple office laboratory testing and
      albuterol administration.

PMID- 16796499
TI  - Dial "T" for testing: Technological flexibility in neuropsychological assessment.
AB  - Computer-automated neuropsychological testing can be conducted over the telephone
      via interactive voice response (IVR) technology by adapting cognitive measures
      traditionally administered by a clinician or in paper-and-pencil formats. By
      utilizing automated telephone interviews in neuropsychological research, time and
      money can be saved, and patients can be assessed remotely. This paper reviews the
      use of IVR to assess neuropsychological functioning in six studies that examined
      alcohol impairment of mental and physical functioning, cognitive and psychomotor
      recovery after surgery, and impairment resulting from central nervous system
      disease. Future directions for expanding application of cognitive performance
      assessment via IVR are discussed.

PMID- 16796500
TI  - Telehomecare for vulnerable populations: The evaluation of new models of care.
AB  - The use of telehomecare has the potential to facilitate access to healthcare
      services for vulnerable populations. However, evidence on the implications of
      telehomecare on various aspects related to patients, healthcare professionals,
      organizations, and healthcare systems is still limited. Assessing the various
      effects of telehomecare for these different groups of stakeholders is thus an
      essential step to ensure future integration of this technology into mainstream
      healthcare services. A synthesis of lessons learned from the evaluation of three
      telehomecare experimentations targeting specific vulnerable groups is proposed.
      This paper presents the various models that were implemented to assess
      telehomecare services for vulnerable populations, explores issues related to
      conducing telehomecare evaluations, and provides a reflection on key factors that
      might influence the success of telehomecare projects. Lessons learned from these
      three experimentations provide valuable insights to orient the development of
      telehomecare services for various vulnerable groups in the population.

PMID- 16796501
TI  - The role of telemedicine and information technology in the redevelopment of
      medical systems: The case of Kosova.
AB  - The medical system of Kosova was largely destroyed in 1999 by the departing
      Serbian forces, leaving behind Albanian physicians systematically excluded from
      advanced medical services for a decade and medical facilities severely damaged in
      the course of departure in a region with an infrastructure fragmented over the
      years. The medical system of Kosova can be analyzed for the effectiveness of the
      many efforts following the disruption of medical care in the 1990s. In this
      paper, the application of telemedicine and information is recounted. The medical
      system of Kosova was offered the concept of the International Virtual E-Hospital
      and this model was used to support, supplement, and guide a massive program
      development that involved essentially every physician and medical personnel in
      the region. Currently, the Telemedicine Center of Kosova (TCK) is providing
      information resources for medical education programs within the Kosova's medical
      system as well as regional and international consultations and collaboration.
      Furthermore, it is developing the human resources that will lead and implement
      telemedicine programs in this region and making serious strides in the
      redevelopment of medical systems using information technology.

PMID- 16796502
TI  - Randomized clinical trial of telepsychiatry through videoconference versus face
      to-face conventional psychiatric treatment.
AB  - Although telepsychiatry in the form of videoconferencing has been well received
      in terms of increasing access to care and user satisfaction, few data on
      treatment outcomes and efficacy from telepsychiatry applications are available at
      the present time. This paper evaluates the efficacy of telepsychiatry through
      videoconference in the treatment of mental disorders by comparing to face-to-face
      conventional (F2FC) treatment. We carried out a randomized clinical trial where
      140 psychiatric outpatients were randomized to either F2FC treatment or
      videoconference telepsychiatry (VCTP) treatment. Patients were diagnosed
      according to International Classification of Diseases, 10th edition (ICD-10)
      criteria using the Composite International Diagnostic Interview. Treatment
      involves eight consultations lasting 30 minutes over the 24-week study period.
      Patients received pertinent psychotropic medication plus cognitive- behavioral
      therapy during sessions. The same psychiatrist diagnosed and treated all the
      patients that were recruited from the Community Mental Health Centre of San
      Sebastian de la Gomera, in the Canary Islands. Change in psychiatric test scores
      served as the primary efficacy criterion. Efficacy was determined by comparing
      baseline (visit 1) Clinical Global Impressions-Severity of Illness (CGI-S) and 
      Improvement (CGI-I) scales as well as Global Indexes (GSI, PSDI, and PST) from
      SCL-90R with scores obtained at the end of the study period (week 24). Response
      was defined as a CGI-I score of 1 or 2. Reliable Change Indexes were computed in
      SCL-90R Global Indexes scores. Of 140 patients randomized, 130 completed 24 weeks
      of treatment. Only 4 patients dropped out prematurely from the study in VCTP and
      6 in F2FC. The study involves 534 teleconsultations, 522 F2FC consultations, and
      more than 500 hours of clinical practice. Significant improvements were found on
      the CGI and SCL-90- R Global Indexes scores of both treatment groups, showing
      clear clinical state improvement. No statistically significant differences were
      observed when the efficacy of VCTP treatment was compared to F2FC psychiatric
      treatment efficacy. This study demonstrated that telepsychiatry treatment through
      videoconference has equivalent efficacy to F2FC psychiatric treatment.
      Telepsychiatry showed to be an effective mean of delivering mental health
      services to psychiatric outpatients living in remote areas with limited
      resources.

PMID- 16796503
TI  - Multimedia data capture and management for surgical events: Evaluation of a
      system.
AB  - The objective of this study was to design an electronic form of documentation of
      surgical procedures, which would include audio and video recording of the entire
      surgical procedure. Video clips have shown promise for teaching surgical
      procedures. To date, no systems have been described to fully record video and
      audio of all events during a surgical procedure. Much as such systems have aided
      the airline industry, surgical safety, documentation, and education could benefit
      from comprehensive, multimedia documentation systems. Four camcorders provided
      views of: (1) anesthetic monitors, (2) laparoscopic images, (3) room view, and
      (4) surgical field view. All video and audio were combined with real-time written
      documentation of events within a simple, inexpensive database for archiving,
      review, and evaluation. Electronic records provided answers to more than 90% of
      the structured review questions, leaving only 6% unanswered, versus 92%
      unanswerable based on the traditional paper records. This electronic
      documentation system provides a much more comprehensive and easily mined means of
      surgical documentation than traditional paper records.

PMID- 16796504
TI  - Use of the internet by United States heart transplant centers to promote
      transparency in the process of patient selection.
AB  - Organ transplantation is an ethically complex technology, in part because organs
      are very scarce and supply does not meet demand. Organ allocation must use a
      process that is fair, and the process should be open for public review and
      revision. We explored the transparency of the heart transplant patient selection
      process in the United States terming transparency as hospital use of their
      transplant program Web site to disclose their policies to potential patients. The
      Web sites of all heart transplant centers belonging to the U.S. Organ Procurement
      and Transplantation Network were reviewed for content pertaining to patient
      selection criteria for placement on the transplant waiting list. All 132 heart
      transplant centers have a Web site that discusses their transplant program;
      however, 84% (n = 111) do not publish their medical listing criteria on their Web
      site. Only 15% (n = 20) expressly indicate the requirement for a psychosocial
      evaluation. Few centers (n = 9) utilize their Web site to discuss use of a formal
      data review committee to decide which patients to list for transplantation. In
      order to demystify and correct false assumptions about the transplant listing
      process, wait listing criteria should be transparent to the public and Internet
      disclosure can facilitate this end. Our findings lay the foundation for future
      prospective studies.

PMID- 16796505
TI  - Impacts of telehomecare on patients, providers, and organizations.
AB  - Over the last decades, development of home care services is an important
      component of ongoing health care systems reforms. However, their full integration
      into hospital or primary care services is still progressing slowly. It appears
      that telehomecare (THC) could help create networks of services between hospital
      and primary care providers. Even though their potential to increase access to
      services and improve quality of care and health outcomes is recognized, their
      widespread adoption has not yet been achieved. Various barriers need to be
      overcome. In this paper, we present our comparative exploratory process analysis
      of the use of THC to follow the treatment of elderly people suffering from severe
      chronic conditions (chronic obstructive pulmonary disease [COPD], hypertension,
      cardiac insufficiency). The technology was first introduced as a pilot project in
      three sites (one site in Quebec and two sites in Manitoba, Canada). Our study is
      based on qualitative methods. It includes a longitudinal analysis of
      implementation processes and monitoring of results. Our analysis allows us to
      identify some of the major impacts on patients and providers, and explain how
      they may be achieved. Also, because of the major changes in work processes, THC
      introduces new models of home care delivery. Two models are identified: a
      specialized model and a planned polyvalent model. Such profound changes raise two
      major challenges for managers and providers. First, the organisation of work,
      traditionally based upon preestablished intervention plans, must adapt to respond
      to ad hoc patients' needs and alerts. Second, constant linkages between the
      traditional and new models of services delivery become mandatory.

PMID- 16796506
TI  - Home-based behavioral health intervention: Use of a telehealth model to address
      poor adherence to type-1 diabetes medical regimens.
AB  - Youth with insulin-dependent diabetes mellitus face complex treatment regimens
      and often have difficulty adhering to treatment requirements. Many behavioral
      health intervention strategies, such as psychoeducational groups, diabetes summer
      camps, individual therapy, and residential treatment have been utilized to
      address this issue. While some have been effective, many barriers exist that
      limit the number of youth who are able to utilize these treatments. Additionally,
      the effectiveness of these treatments does not typically generalize to the home
      environment. Telephone-based, intensive, behavioral-health interventions may
      address barriers to treatment access by providing lower cost treatment that is
      easier to access for youth who do not live near a knowledgeable behavioral-health
      specialist. Additionally, delivery via telephone enables the interventions to
      take place in the home. This, in combination with parental involvement in the
      treatment, may increase generalization of the positive treatment outcomes to the
      home environment. The purpose of this paper is to describe a controlled trial of
      a telehealth intervention for youth whose diabetes is poorly managed. Preliminary
      outcome data for the trial are promising. Representative cases from the trial are
      presented in case-study format.

PMID- 16796507
TI  - Wireless technologies and patient safety in hospitals.
AB  - In the development of policies for wireless technologies, it is important for
      healthcare organizations to reduce risks to patients from use of wireless
      devices. Policy should be devised for instructing hospital staff, visitors, and
      patients, avoiding unwarranted restrictions but not ignoring evidence regarding
      potential interference problems, and allowing comparison with other clinical
      facilities of benefits of policy. To inform policy developers and a general
      audience of hospital personnel, a review was conducted on the safety of wireless
      devices for communication within hospitals. This review targeted electromagnetic
      interference effects of devices on medical devices and summarises key
      recommendations from published reports and international standards. There is
      consensus that the highest risk of interference occurs with two-way radios used
      by emergency crews, followed by mobile phones, while radio local area networks
      produce negligible interference. Wireless technologies are deemed suitable for
      use throughout hospital areas including intensive care units and operating rooms,
      given that recommended separation distances from medical equipment are observed.

PMID- 16796508
TI  - The 2005-2006 Chikungunya epidemic in the Indian Ocean.

PMID- 16796509
TI  - Efficacy of resmethrin aerosols applied from the road for suppressing Culex
      vectors of West Nile virus.
AB  - We determined whether aerosol applications of resmethrin, delivered from the
      road, suppress the reproductive activity of Culex pipiens pipiens and Cx.
      restuans mosquitoes in suburban sites located near Boston. Oviposition implies a
      prior blood-feeding event and hence a potential West Nile virus (WNV)
      transmission-related event. Droplet size, rate of delivery and meteorological
      conditions were monitored. The target populations proved to be fully susceptible
      to the insecticide that was used. The roads in the test sites generally gave
      adequate opportunity for insecticidal coverage. We found that the aerosol plume
      may have failed to contact the target mosquitoes and conclude that such
      insecticidal aerosols, delivered from the road, may not effectively reduce the
      force of transmission of WNV in our test sites.

PMID- 16796510
TI  - Modeling movement of West Nile virus in the Western hemisphere.
AB  - We modeled West Nile virus (WNV) movement rates and patterns based on a migratory
      bird agent (the Swainson's Thrush) and a resident bird agent (the House Sparrow),
      and compared the results of these models with actual movement data to investigate
      the likelihood that the pattern of WNV outbreaks observed in the New World was
      consistent with migrant bird-mediated spread, as reported from the Old World. We
      found that, contrary to Old World patterns, WNV activity in the Western
      Hemisphere does not seem consistent with movement by infected migrant birds.
      Instead WNV spread appears best explained by a non-directional movement, perhaps
      that of dispersing resident birds.

PMID- 16796511
TI  - Co-infection of white-tailed deer with multiple strains of Ehrlichia chaffeensis.
AB  - We investigated the effect of exposing deer to multiple strains of Ehrlichia
      chaffeensis that differed in number of tandem repeats in either the variable
      length PCR target (VLPT) gene or 120 kDa antigen gene. We hypothesized that
      infection with one strain would provide immunity to infection with other strains
      of E. chaffeensis. All deer initially exposed to strain A (604-2) became PCR and
      culture positive by 10 days post-infection (DPI). Three deer infected with strain
      A and subsequently inoculated with strain B (623-4) became infected with strain
      B. Two deer infected with strain A and subsequently inoculated with strain C
      (125B) became infected with strain C. Of three deer, each infected with strain B
      and subsequently inoculated with strain C, one was PCR positive for strain C. Of
      three deer previously inoculated with both strains A and B, and subsequently
      inoculated with strain C, one showed delayed evidence of strain C. Western blot
      analysis demonstrated that deer sera reacted differently to antigens from each
      exposed strain. A complementary in vitro study demonstrated that exposure to two
      strains differing in VLPT repeats may lead to co-infection of DH82 cells. These
      results complement a previous study and further show that deer can become
      sequentially infected with up to three strains of E. chaffeensis. This suggests
      that competitive exclusion, a phenomenon described in related organisms such as
      Anaplasma marginale whereby infection with one strain precludes subsequent
      infection by a second, distinct strain of the same species, may not occur with E.
      chaffeensis.

PMID- 16796512
TI  - A novel real-time PCR assay for the speciation of medically important ticks.
AB  - The identification of ticks using morphological characters is a well-established
      practice, however specimens that are small or damaged are often difficult to
      speciate. A novel, rapid real-time PCR assay, which targets the second internal
      transcribed spacer (ITS2) region in the nuclear ribosomal DNA gene, was developed
      for identification of four tick species of utmost medical importance in the
      United States: Ixodes scapularis, I. pacificus, Dermacentor variabilis, and
      Amblyomma americanum. Computational analyses of public databases and DNA
      sequencing studies revealed regions that could be specifically targeted with
      oligonucleotides optimized for TaqMan chemistry. The oligonucleotide sets
      designed in this study are specific at both the genus and species levels, and are
      sensitive at 0.1-1 pg of total tick DNA.

PMID- 16796513
TI  - Syndromic surveillance in the Netherlands for the early detection of West Nile
      virus epidemics.
AB  - West Nile virus (WNV) is an arthropod-borne flavivirus that is endemic in Africa,
      Europe, and Eastern Asia. The recent introduction and rapid dissemination of the
      virus in the United States as well as an increase in WNV outbreaks in Europe, has
      raised concerns for its spread in Europe. A surveillance system was developed to
      allow timely detection of an introduction of WNV infections in The Netherlands.
      This program focuses on cases presenting with neurological disease and includes
      the monitoring of hospital discharge diagnoses, trends in cerebrospinal fluid
      (CSF) diagnostic requests, laboratory testing of CSF, and monitoring of
      neurological disease in horses. Retrospective data from the hospital discharge
      records showed yearly peaks of unexplained meningitis and (meningo)encephalitis
      in the summer. A total of 781 CSF samples from humans and 71 serum and/or CSF
      samples from horses presenting with neurological disease of suspected viral
      etiology tested negative for the presence of specific antibodies to WNV. With a
      coverage rate of 59% in 2003, the probability that a cluster of five WNV cases
      presenting with neurological symptoms would have been detected was 99%. We
      conclude that, from 1999 to 2004, no evidence of WNV infection could be found in
      either humans or horses in The Netherlands.

PMID- 16796514
TI  - Rocky Mountain spotted fever in the United States, 1997-2002.
AB  - Rocky Mountain spotted fever (RMSF) is the most commonly reported fatal tick
      borne disease in the United States. During 1997-2002, 3,649 cases of RMSF were
      reported to the Centers for Disease Control and Prevention via the National
      Electronic Telecommunications System for Surveillance; 2,589 case report forms,
      providing supplemental information, were also submitted. The average annual RMSF
      incidence during 1997-2002 was 2.2 cases/million persons. The annual incidence
      increased during 1997-2002 to a rate of 3.8 cases/million persons in 2002. The
      incidence was lowest among persons aged<5 and 10-29 years, and highest among
      adults aged 60-69 years. The overall case-fatality rate was 1.4%; the rate peaked
      in 1998 at 2.9% and declined to 0.7% in 2001 and 2002. Children<5 years of age
      had a case-fatality rate (5%) that was significantly greater than the rates for
      age groups<60 years of age, except for that for 40-49 years of age. Continued
      national surveillance is needed to assess the effectiveness of prevention efforts
      and early treatment in decreasing severe morbidity and mortality associated with
      RMSF.

PMID- 16796515
TI  - Domestic animals as carriers of Bordetella species in Senegal.
AB  - Despite intense efforts to maintain a high level of vaccine coverage against
      human whooping cough, rural senegalese areas are still endemic for Bordetella
      pertussis. One explanation being the potential existence of animal reservoirs,
      the objective of this work was to precise the carriage by domestic animals of
      bacteria belonging to the genus Bordetella in Senegal. Bacteriological samples
      (swabs and aspirates) were obtained from various domestic animals living in
      different parts of the country. No B. pertussis nor B. parapertussis were
      isolated. However, for the first time to our knowledge, B. bronchiseptica was
      identified from small ruminants located in Africa. The positive animals were two
      goats and two sheep from Dakar slaughterhouse together with a goat living in a
      rural compound. The fact that it was identified in goats and sheep underlines the
      potential zoonotic of that bacterial species in countries where small ruminants
      are of economical and cultural relevance.

PMID- 16796516
TI  - Field and laboratory evaluation of diagnostic assays for detecting West Nile
      virus in oropharyngeal swabs from California wild birds.
AB  - Three diagnostic assays for detecting West Nile virus (WNV) in avian oral swabs
      were evaluated in California in 2004 and 2005: two commercial antigen-capture
      assays, VecTest and Rapid Analyte Measurement Platform (RAMP), and reverse
      transcriptase-polymerase chain reaction (RT-PCR) of oral swabs in a specialized
      viral transport medium (VTM). Results from this study demonstrated that VTM was
      excellent for transportation and maintenance of WNV in avian oral swab samples
      and allowed for detection by RT-PCR and subsequent confirmation by virus
      isolation. Oral swabs and kidney tissue in VTM tested by RT-PCR were found to
      have similar accuracy in detecting WNV in corvids. The two antigen-capture
      assays, VecTest and RAMP, provided few false positives for corvids, with over 95%
      specificity. When performed by multiple local agencies throughout the state,
      VecTest and RAMP were similarly sensitive for oral swabs of American Crows
      (Corvus brachyrhynchos) (70% and 64%, respectively). Data from known WNV positive
      corvid oral swabs in VTM tested by antigen-capture assays at a diagnostic
      laboratory suggested that RAMP was more sensitive than VecTest. Due to high
      probability of false negatives, neither test is recommended for use on non
      corvids. While WNV antigen-capture assays were effective screening tools for
      corvids, they were markedly less sensitive for Western Scrub Jays (Aphelocoma
      californica).

PMID- 16796518
TI  - Circumstances of bat encounters and knowledge of rabies among Minnesota residents
      submitting bats for rabies testing.
AB  - Minnesota residents who submitted a bat to the Minnesota Department of Health for
      rabies testing in 2003 were surveyed by telephone regarding the circumstances of
      the bat encounter and their knowledge of bats and rabies. Of 442 bats submitted
      for testing, 12 (3%) tested positive for rabies, and 410 (93%) tested negative;
      17 (4%) bats were unsuitable for testing, and three (1%) had equivocal results. A
      case-control study found that rabid bats were more likely than non-rabid bats to
      be found in September, found outside, found in a wooded area, unable to fly,
      acting ill, or acting aggressively. Rabid bats were not more likely than non
      rabid bats to be found during the day or to have bitten someone. While most
      persons submitting bats for rabies testing were aware that bats can carry rabies,
      few knew they should submit the bat for testing until they sought the advice of
      an animal control officer, veterinarian, or healthcare provider.

PMID- 16796517
TI  - Evaluation of white-tailed deer (Odocoileus virginianus) as natural sentinels for
      Anaplasma phagocytophilum.
AB  - Anaplasma phagocytophilum, the causative agent of human granulocytotropic
      anaplasmosis, can infect white-tailed deer (WTD; Odocoileus virginianus), and
      this species is a crucial host for adult Ixodes scapularis, the primary vector of
      A. phagocytophilum. The goal of this study was to determine the geographic
      distribution of A. phagocytophilum among WTD across a 19 state region and to
      evaluate the utility of WTD as natural sentinels. Serologic testing using the
      indirect fluorescent antibody (IFA) assay was conducted on WTD serum samples and
      molecular and xenodiagnostic tests were performed to confirm serologic results.
      The surveillance system was assessed through examination of vital attributes
      including WTD age and gender associations with serologic status, sample size
      adequacy for accurate infection status classification, and presence of the
      vector, I. scapularis. Six hundred thirty-three of 2,666 (24%) WTD in 17 states
      tested positive for antibodies (>or=128) when tested by IFA assay. Testing for
      p44 and/or 16S rRNA gene targets identified 73 (16%) PCR positive WTD among 458
      animals tested, all of which originated from seropositive populations. Attempts
      to culture A. phagocytophilum from WTD were unsuccessful; however, xenodiagnostic
      mice inoculated with blood from 3 WTD became infected. Seroprevalence did not
      differ by deer age or gender; however, WTD<or=0.75 years old had a higher
      prevalence of PCR positivity. Using seroprevalence data, a sample size of 6-9
      animals per population was projected to be adequate for identifying seropositive
      populations. The presence of I. scapularis was significantly associated with A.
      phagocytophilum antibodies in WTD. Collectively, the results of this study
      demonstrate that WTD would be suitable natural sentinels for this emerging
      zoonotic pathogen.

PMID- 16796520
TI  - Interview with Daniel E. Sonenshine, Ph.D. Interview by Vicki Glaser.

PMID- 16796519
TI  - Larvicidal diterpenes from Pterodon polygalaeflorus.
AB  - Ethanolic extract from seeds of Pterodon polygalaeflorus (Benth) has been shown
      to possess significant larvicidal activity against the mosquito Aedes aegypti.
      Bioassay-guided fractionation of the extract led to the isolation and
      characterization of the know diterpenoid furans 6alpha-hydroxyvouacapan
      7beta,17beta-lactone (1), 6alpha,7beta-dihydroxyvouacapan- 17beta-oic acid (2)
      and methyl 6alpha,7beta-dihydroxyvouacapan-17beta-oate (3). The structures were
      established from infrared (IR), ultraviolet (UV), 1H-nuclear magnetic resonance
      (NMR), 13C-NMR, and mass spectral data: full NMR assignments are presented for
      compounds 1-3 and the diacetyl derivative of 3. Compounds 1-3 exhibited LC50
      values of 50.08, 14.69, and 21.76 microg/mL against fourth-instar Aedes aegypti
      larvae.

PMID- 16796521
TI  - An immunoglobulin fusion protein based on the gp120-CD4 receptor complex potently
      inhibits human immunodeficiency virus type 1 in vitro.
AB  - Fusion proteins containing immunoglobulin Fc domains attached to bioactive
      moieties have been developed as therapeutic agents against several diseases.
      Here, we describe the development and characteristics of a novel fusion protein
      (FLSC R/T-IgG1) that targets CCR5, the major coreceptor for HIV-1 during primary
      infection. FLSC R/T-IgG1 was expressed from a synthetic gene that linked a single
      chain gp120-CD4 complex containing an R5 gp120 sequence with the hinge-CH2-CH3
      portion of human immunoglobulin gamma subtype 1. Purified FLSC R/T-IgG1 exhibited
      a molecular mass of 189 kDa under reducing conditions, which matched the expected
      size of one polypeptide chain. Chemically crosslinked or untreated FLSC R/T-IgG1
      exhibited a mass of a 360-kDa polypeptide under reducing and nonreducing
      conditions, which indicated that the molecule adopts a disulfide-linked bivalent
      structure. The chimeric molecule bound specifically to CCR5-expressing cells and
      to peptides derived from the CCR5 N-terminus. Such binding was more efficient
      than what was obtained with a monomeric single chain gp120-CD4 complex. FLSC R/T
      IgG1 binding to CCR5 was blocked by preincubation of coreceptor-expressing cells
      with CCR5 ligands and by antibody to the coreceptor binding domain of gp120.
      Conversely, FLSC R/T-IgG1 blocked the binding of chemokine to CCR5. However, FLSC
      R/T-IgG1 did not trigger intracellular Ca2+ mobilization in peripheral blood
      mononuclear cells. FLSC R/T-IgG1 potently neutralized primary R5 HIV-1 in both a
      PBMC-based assay and cell line-based assays but did not affect the replication of
      X4 viruses. These findings suggest that FLSC R/T-IgG1 might be used as a possible
      therapeutic agent against HIV.

PMID- 16796523
TI  - No influence of GB virus C on disease progression in a Danish cohort of HIV
      infected men.
AB  - Presumed apathogenic viruses have been suggested to play a role in HIV infection.
      In some cohorts of HIVpositive patients, GB virus C (GBVC) has been associated
      with prolonged survival and time to AIDS. We set out to address whether GBVC
      infection had any influence on survival in a cohort of 112 homosexual white HIV-1
      positive Danish men. Patients were enrolled between 1984 and 1987 and followed
      for a mean of 6.7 years. Follow-up was censored in May 1996 when the first
      patient in the cohort received HAART. Plasma samples were screened at baseline
      using polymerase chain reaction methods for GBVC. Of the 112 patients, 27 (24%)
      were positive for GBVC. No difference in time to AIDS or death was observed
      between the GBVCnegative and -positive patients. Furthermore, no difference in
      CD4+ T cell decline was observed in the first year following blood sampling
      between the GBVC-positive and -negative groups.

PMID- 16796522
TI  - Pediatric HIV type 1 vaccine trial acceptability among mothers in Kenya.
AB  - Vaccination of infants against human immunodeficiency virus type 1 (HIV-1) may
      prevent mother-to-child HIV-1 transmission. Successful trials and immunization
      efforts will depend on the willingness of individuals to participate in pediatric
      vaccine research and acceptance of infant HIV-1 vaccines. In a cross-sectional
      study, pregnant women presenting to a Nairobi antenatal clinic for routine care
      were interviewed regarding their attitudes toward participation in research
      studies and HIV-1 vaccine acceptability for their infants. Among 805 women, 782
      (97%) reported they would vaccinate their infant against HIV-1 and 729 (91%)
      reported willingness to enroll their infant in a research study. However, only
      644 (80%) would enroll their infants if HIV- 1 testing was required every 3
      months and 513 (64%) would agree to HIV-1 vaccine trial participation. Reasons
      for not wanting to enroll in a pediatric HIV-1 vaccine trial included concerns
      about side effects (75%), partner objection (34%), and fear of discrimination
      (10%), HIV-1 acquisition (8%), or false-positive HIV-1 results (5%). The
      strongest correlate of pediatric vaccine trial participation was maternal
      willingness to be a vaccine trial participant herself; in univariate and
      multivariate models this was associated with a 17-fold increased likelihood of
      participation (HR 17.1; 95% CI 11.7-25; p < 0.001). We conclude from these
      results that immunizing infants against HIV-1 and participation in pediatric
      vaccine trials are generally acceptable to women at high risk for HIV-1
      infection. It will be important to address barriers identified in this study and
      to include male partners when mobilizing communities for pediatric HIV-1 vaccine
      trials and immunization programs.

PMID- 16796524
TI  - Rabbit retrotransposon sequences undetectable in blood donors and lymphoma
      patients of the Swiss HIV Cohort Study.

PMID- 16796526
TI  - The N-terminal SRCR-SID domain of gp-340 interacts with HIV type 1 gp120
      sequences and inhibits viral infection.
AB  - Proteins encoded by the SRCR superfamily including gp340 recognize repeated
      patterns on pathogenic microorganisms and play important roles in innate immune
      defense as well as epithelial cell differentiation. Based upon the presence of
      SRCR domains in proteins with broad binding specificities and high amino acid
      sequence homology, it was speculated that SRCR domains may be involved in ligand
      binding. In this study, a truncated gp340 molecule representing the N-terminal
      sequence including the first SRCR and one-half of the first SID was expressed in
      mammalian 293 cells as a 35-kDa recombinant protein. The expressed protein was
      recognized by a panel of antibodies specific for human salivary agglutinin (SAG)
      and the full-length parental gp340 and exhibited biological properties similar to
      the entire 340-kDa glycoprotein. The truncated gp340 protein bound to the same
      HIV-1 V3 sequences previously identified to interact with full-length SAG in a
      Ca2+ -dependent manner. The recombinant N-terminal SRCR protein also demonstrated
      potent anti-HIV- 1 activity against both CCR5- and CXCR4-using isolates, similar
      to the full-length glycoprotein. We have, thus, demonstrated that the N-terminal
      SRCR of gp340 directly interacts with viral gp120 and likely mediates anti-HIV-1
      activity via this interaction.

PMID- 16796525
TI  - Longitudinal assessment of de novo T cell production in relation to HIV
      associated T cell homeostasis failure.
AB  - Loss of circulating CD4+ T cells in HIV-1 disease is balanced by CD8+
      lymphocytosis to maintain normal CD3+ T cell counts [blind T cell homeostasis
      (TCH)]. However, for unknown reasons TCH generally fails 1.5-2.5 years before
      clinically defined AIDS. We investigated whether TCH failure was associated with
      changes in thymic production of T cells. Using specimens stored prospectively in
      the Multicenter AIDS Cohort Study (MACS), we measured expression of signal-joint
      T cell receptor excision circles (sjTRECs), a marker for thymic T cell
      production, and the fraction of proliferating naive and memory T cells during a 6
      8 year period bracketing TCH failure. Segmented regression modeling assessed (1)
      rates of change in TREC levels before and after TCH failure, and (2) whether
      these were affected by cellular proliferation, which may dilute sjTREC levels.
      TCH failure was associated with a large decline in sjTREC (median 1109-fold, p =
      0.028); the rate of this decline was only slightly affected when increased
      proliferation of naive T cells or other peripheral lymphocytes was taken into
      account. Preferential loss of naive CD4+ T cells was also noted before TCH
      failure, as has been seen in other studies. These results suggest that deficits
      in de novo T cell production, either through the decline of thymic function or
      the destruction of naive T cells, are likely to play an important role in TCH
      failure and progression of HIV-1 disease.

PMID- 16796527
TI  - Long lasting control and lack of pathogenicity of the attenuated Rev-independent
      SIV in rhesus macaques.
AB  - A cohort of 22 rhesus macaques of Indian origin infected as neonates, juveniles,
      or adults by Rev-independent strains of SIV was monitored over several years.
      After the initial acute phase, virus replication was controlled and plasma virus
      loads were persistently below the threshold of the assay. The animals were
      monitored for up to 7.6 years after infection for viral loads, cellular and
      humoral immune responses, hematological changes, and overall health and no signs
      of immune dysfunction or AIDS were observed. This study represents several years
      of additional observation compared to the previously published results, and
      indicates that the Rev-independent SIV clones tested do not cause AIDS-like
      progressive disease within 7.6 years from infection. All the animals showed
      persistent humoral and cellular SIV-specific immune responses, consistent with
      chronic infection. Different Rev-independent SIV strains showed similar
      properties and lack of pathogenicity. Multicolor flow cytometric analysis
      demonstrated preservation of the Central Memory subset of T cells in the
      attenuated SIV-infected animals. This study demonstrates a potent, long-lasting
      control of the Rev-independent attenuated SIV in macaques independent of the age
      at virus exposure.

PMID- 16796528
TI  - SIV-associated myocarditis: viral and cellular correlates of inflammation
      severity.
AB  - Myocarditis is a common finding in HIV-infected people. Cardiac inflammatory
      lesions and functional abnormalities similar to those documented in HIV infection
      are frequently seen in SIV infection of rhesus monkeys, suggesting a shared
      disease mechanism. A retrospective analysis of cardiac tissue collected at
      necropsy was performed to assess correlates of myocardial inflammation in SIV
      infected rhesus monkeys. Intramyocardial SIV-infected cells were identified in 7
      of 21 hearts from SIV-infected animals, with viral protein consistently
      colocalizing with the macrophage marker HAM 56. Productively infected cells
      occurred in low numbers, and did not correlate with the presence or quantity of
      inflammation or necrosis. Intramyocardial CMV was identified in 6 of 21 hearts
      from SIV+ animals, but also did not correlate with the presence or quantity of
      inflammation or necrosis. In contrast, T cell infiltration correlated inversely
      with DC-SIGN+ cell numbers, which occurred in significantly higher numbers in
      SIV+ animals with histologically normal myocardium than in SIV+ animals with
      active or borderline myocarditis or in uninfected controls (p < 0.001),
      suggesting an important immunoregulatory role for this population within the
      myocardium.

PMID- 16796529
TI  - APOBEC3G expression is restricted to neurons in the brains of pigtailed macaques.
AB  - The Vif protein of human immunodeficiency virus-1 (HIV-1) has been shown to
      interact with members of the APOBEC family of cytidine deaminases, particularly
      APOBEC3G/F. In this study, we isolated RNA from 12 regions of the brain from two
      pigtailed macaques that were exsanguinated and perfused with saline. Our results
      indicate that APOBEC3G was detected in all regions of the brain analyzed.
      Immunoblot analysis using lysates prepared from these same regions of the brain
      and a monoclonal antibody to APOBEC3G confirmed the RT-PCR findings. To determine
      which cell types express APOBEC3G, immunohistochemical studies were performed
      using this monoclonal antibody on whole brain sections. Our results clearly show
      that the pyramidal neurons within the gray matter of cerebral and cerebellar
      cortices express APOBEC3G. However, APOBEC3G expression in the pyramidal neurons
      appeared to be nuclear or associated with nuclei. In contrast to our findings in
      the cerebral cortex, immunohistochemical analysis of the spleen and kidney
      tissues revealed that APOBEC3G expression in the cells of these tissues was
      predominantly cytoplasmic. We further investigated the expression of APOBEC3G in
      astrocytes. Immunohistochemical staining of serial sections was performed using
      antibodies to glial fibrillary acidic protein (GFAP) and APOBEC3G. As expected,
      the cortical and cerebellar white matter showed extensive immunostaining of
      astrocytes with the antibody against GFAP but a lack of reactivity to the
      antibody to APOBEC3G. Additionally, Immunoblot analysis of lysates prepared from
      primary human fetal astrocytes revealed a lack of APOBEC3G expression. Taken
      together, these results indicate that APOBEC3G expression is restricted to
      neurons in the brain and that astrocytes and microglia probably do not express
      this protein or express it at levels undetectable by immunohistochemistry. These
      finding have implications for the brain as a potential reservoir for Vif
      defective viruses.

PMID- 16796530
TI  - Expression of human endogenous gammaretroviral sequences in endometriosis and
      ovarian cancer.
AB  - Endogenous retroviruses (ERVs) probably originate from ancient germ cell
      infections by exogenous retroviruses. A high expression of retroviruses in
      reproductive tissue increases the risk of viral transmission to germ line cells.
      We therefore investigated the expression of human ERVs (HERVs) in normal
      endometrium, endometriosis, normal ovaries, and ovarian cancer. Four real-time
      PCRs (QPCRs) for HERV-E, HERV-I/T, HERV-H, and HERV-W, respectively, and an
      expression control gene were used. HERV-E RNA expression was significantly higher
      in endometriotic tissue (average, SD) than in normal endometrium (average, SD),
      both measured as ratios versus control gene expression and as. HERV-E and HERV-W
      RNA were higher in normal ovarian tissue than in ovarian cancer. This illustrates
      that HERV expression is not automatically higher in malignant tissues. The other
      HERV PCRs did not show expression patterns as distinctive as HERVE and HERV-W in
      the two kinds of reproductive tissue. A small number of candidate HERV-E loci
      from which the transcription took place were identified by sequencing of
      amplimers. The role of HERV-E and HERV-W in endometriosis merits further
      investigation.

PMID- 16796531
TI  - Capric acid and hydroxypropylmethylcellulose increase the immunogenicity of
      nasally administered peptide vaccines.
AB  - Immunization by the nasal route is an established method for the induction of
      mucosal and systemic humoral and cell-mediated antigen-specific responses.
      However, the effectiveness of nasal immunization is often hampered by the need
      for increased doses of antigen. Bioadhesives and absorption enhancers were
      investigated for their ability to enhance immune responses in mice after nasal
      immunization with model HIV-1 peptide and protein immunogens. Two additives,
      hydroxypropylmethylcellulose (HPMC) and capric acid, consistently enhanced
      antigen-specific serum IgG endpoint titers under conditions in which antigen dose
      was limiting. Nasal immunization of mice with 20 microg of an HIV-1 peptide
      immunogen plus cholera toxin (CT) as adjuvant induced serum antipeptide IgG
      titers of 1:9.5log2 after four immunizations while the addition of CA or HPMC to
      the vaccine formulation increased serum antipeptide IgG titers to 1:15.4log2 and
      1:17.6log2, respectively. When 5 microg recombinant HIV-1 gp41 was used as the
      immunogen, the addition of CA or HPMC to the vaccine formulation increased serum
      anti-gp41 IgG titers to 1:11.6log2 and 1:8.8log2, respectively, compared to
      1:5.2log2 after three nasal immunizations with 5 microg gp41 + CT alone. Thus,
      HPMC and capric acid may be useful additives that increase the immunogenicity of
      nasally administered vaccines and permit less antigen to be used with each
      immunization.

PMID- 16796532
TI  - Construction and characterization of soluble, cleaved, and stabilized trimeric
      Env proteins based on HIV type 1 Env subtype A.
AB  - The generation of an antibody response capable of neutralizing a broad range of
      clinical isolates remains an important goal of human immunodeficiency virus type
      1 (HIV-1) vaccine development. Envelope glycoprotein (Env)-based vaccine
      candidates will also need to take into account the extensive genetic diversity of
      circulating HIV-1 strains. We describe here the generation of soluble,
      stabilized, proteolytically cleaved, trimeric forms of Env (SOSIP gp140 proteins)
      based on contemporary Env subtype A viruses from East Africa. We discuss issues
      associated with the construction, purification, and characterization of such
      complex proteins; not all env sequences allow the expression of trimeric
      proteins. However, stabilized trimers from one such protein, KNH1144 SOSIP gp140,
      were successfully made. These proteins are now being prepared for preclinical
      immunogenicity studies.

PMID- 16796533
TI  - Comparative evaluation of simian, simian-human, and human immunodeficiency virus
      infections in the pigtail macaque (Macaca nemestrina) model.
AB  - The global impact of HIV/AIDS intensifies the need for a preventive vaccine and
      nonhuman primate models can help provide critical insights into effective
      immunity. Pigtail macaques (Macaca nemestrina) are increasingly studied as a
      nonhuman primate model for AIDS. We compared the virologic and immunologic
      characteristics of HIV-1, SIV, and SHIV infection of naive pigtail macaques
      across a series of preclinical HIV vaccine studies. SIVmac251 and SIVmac239
      infection of naive pigtail macaques resulted in a gradual decline in peripheral
      CD4+ T cells in the setting of high levels of viremia, approximating most closely
      human infection of HIV-1. In contrast, the CXCR4-utilizing SHIVmn229 virus
      resulted in rapid depletion of CD4+ T cells and minimal generation of humoral or
      cellular immune responses, similar to that observed with SHIV89.6P infection of
      rhesus macaques. Infection with the CCR5-utilizing, rhesus macaque passaged,
      SHIVSF162P3 resulted in some overall CD4+ T cell decline, however, three of eight
      macaques naturally control SHIVSF162P3 viremia to very low levels in the setting
      of robust adaptive immunity. Despite attempts at infecting pigtail macaques with
      HIV-1 strains passaged in juvenile pigtail macaques in vivo or in PBMC isolated
      from pigtail macaques in vitro, only lower nonsustained levels of viral
      replication were observed. Our results provide a series of virologic models with
      which to evaluate potential AIDS vaccines in pigtail macaques.

PMID- 16796535
TI  - High HIV type 1 subtype diversity and few drug resistance mutations among
      seropositive people detected during the 2005 second generation HIV surveillance
      in Madagascar.
AB  - Subtype determination and detection of drug resistant-associated mutations (DRM)
      were performed on 31 HIV-1 Western blot-positive sera during the 2005 second
      generation HIV surveillance in Madagascar. Amplification and sequencing of at
      least one of the partial reverse transcriptase, protease, and partial envelope
      genes were successful for all strains. All three gene sequences were obtained for
      28 strains. A high degree of subtype or circulating recombinant forms (CRF) was
      observed for these 28 strains: A-A1 (eight cases), CRF02_AG (six cases), B (five
      cases), C (three cases), CRF06_cpx (three cases), CRF10_CD, BC()CRF, and unique
      RF (one case each). According to the ANRS September 2005 DRM list and algorithm,
      no DRM was detected in the reverse transcriptase and only one strain bore three
      major DRM in the protease M46I, I84V, and L90M leading to resistance to
      indinavir, saquinavir, nelfinavir, atazanavir/ritonavir, and possibly lopinavir.

PMID- 16796534
TI  - Chronic alcohol consumption results in higher simian immunodeficiency virus
      replication in mucosally inoculated rhesus macaques.
AB  - The influence of alcohol consumption on HIV pathogenesis is not well understood.
      In this study we used the SIV/macaque model of HIV infection to study the
      influence of chronic binge alcohol consumption on simian immunodeficiency virus
      (SIV) infection. Rhesus macaques were fed alcohol or isocaloric amounts of
      sucrose via indwelling intragastric catheters and then inoculated with SIVmac251
      by the rectal route. Real-time RTPCR for SIV gag mRNA showed significantly higher
      plasma viral copies in alcohol-consuming macaques at 4 and 6 weeks pi, compared
      with sucrose controls. The viral copies were 1 to 2 logs higher in these animals.
      The percentage of CD8+ lymphocytes in the duodenum of alcohol-consuming macaques
      was significantly lower than in sucrose-consuming macaques both before infection
      as well as at different time points postinfection. Also, the percentage of
      CD4+CD3+ lymphocytes in the intestines was significantly higher in alcohol
      consuming macaques before infection. These findings suggest that a higher
      percentage of SIV target cells (CD4) in the gut coupled with lower percentages of
      CD8 cells, which could be important in controlling virus replication, may be
      responsible for the higher SIV loads observed in alcohol-consuming macaques.

PMID- 16796536
TI  - Two-dimensional and three-dimensional imaging show ciclesonide has high lung
      deposition and peripheral distribution: a nonrandomized study in healthy
      volunteers.
AB  - Drug deposition is an important factor that contributes to safety and efficacy
      outcomes of inhaled steroid therapy. Ciclesonide is a nonhalogenated, inhaled
      corticosteroid under investigation for the treatment of asthma. Therefore, this
      study was performed to assess lung deposition of ciclesonide. Technetium-99m
      (99mTc)-labeled ciclesonide (where the 99mTc-label is physically dissolved in the
      ciclesonide-hydrofluoroalkane [HFA] solution aerosol) inhaled by healthy
      volunteers was analyzed by two-dimensional (2-D) and three-dimensional (3-D)
      imaging to determine lung deposition. Six healthy volunteers inhaled one puff of
      40 microg (exactuator, equivalent to 50 microg ex-valve) ciclesonide for 2-D
      imaging, and two healthy volunteers inhaled 10 puffs of 40 microg ciclesonide for
      2-D and 3-D imaging. The ciclesonide aerosol was administered via metered-dose
      inhaler (MDI) containing HFA-134a as propellant. The ex-actuator mean (+/-
      standard deviation) deposition of ciclesonide in the lungs was higher (52% +/-
      11%) than in the mouth/pharynx (38% +/- 14%). Two-dimensional and 3-D imaging
      showed that ciclesonide reached all regions of the lung. Mean percent deposition
      in peripheral regions (47% and 34%) was higher than in lower central regions (17%
      and 30%), as revealed by 3-D and 2-D imaging, respectively. Inhalation of up to
      400 microg of ciclesonide produced no drug-related side effects. In conclusion,
      ciclesonide administered via metered-dose inhaler using HFA-134a as a propellant
      provided high lung deposition (>50%), greater distribution throughout peripheral
      regions of the lungs, and relatively low oropharyngeal deposition.

PMID- 16796537
TI  - Prescription bias and factors associated with improper use of inhalers.
AB  - Many different inhalers are available for delivering aerosol therapy in
      respiratory medicine. As a consequence, the prescribing physicians may have some
      difficulty tailoring the most suitable inhaler to each patient. This multicenter,
      observational study using a self-administered questionnaire analyzed the
      characteristics of a large sample of patients (n = 1,305; 55% females; mean age
      57.4, with a range of 15-88 years; most suffering from asthma or chronic
      obstructive pulmonary disease [COPD]) familiar with several different types of
      inhalers in relation to their most commonly used delivery device. Data on the
      inhalation technique for 2,057 observations of 1,126 patients using device
      specific checklists and factors associated to misuse were also evaluated.
      Prevalent usage of newer dry powder inhalers (DPIs) was significantly associated
      with male sex, higher education, better respiratory function, and prescription
      from a respiratory physician. Patients using DPIs had received less instruction
      by health caregivers and were more likely to have read the instruction leaflet
      than users of metered dose inhalers (MDIs). Under these conditions, inhaler
      misuse was common and similar for both pressurized metered dose inhalers (pMDIs)
      and DPIs. For both types of inhalers, misuse was significantly and equally
      associated to increased age, less education, and less instruction by health care
      personnel. We conclude that many doctors are not familiar with the relevant
      characteristics of currently available inhalers. The prescription of newer DPIs
      may be subjected to gender, socio-economic, and instruction bias. The simple
      change of device from the pMDI to the newer DPIs is not associated with improved
      inhalation technique.

PMID- 16796538
TI  - A closed-loop control "playback" smoking machine for generating mainstream smoke
      aerosols.
AB  - A first generation smoking machine capable of reading and replicating detailed
      puffing behavior from recorded smoking topography data is presented. Unlike
      standard smoking machines, which model human puffing behavior as a steady
      periodic waveform with a fixed puff frequency, volume, and duration, this novel
      machine generates a mainstream smoke aerosol by automatically "playing-back" puff
      topography recordings. Because combustion chemistry is highly non-linear,
      representing real smoking behavior with a smoothed periodic waveform may result
      in a tobacco smoke aerosol with a significantly different chemical composition
      and physical properties than that generated by a smoker. The machine presented
      here utilizes a rapid closed-loop control algorithm coded in Labview to generate
      smoke aerosols for toxicological assessment and inhalation studies. To illustrate
      its use, dry particulate matter and carbon monoxide yields generated using the
      playback and equivalent periodic puffing regimens are compared for a single
      smoking session by a 26-year-old male narghile water-pipe smoker. It was found
      that the periodic puffing regimen yielded 20% less carbon monoxide (CO) than the
      played-back smoking session, indicating that steady periodic smoking regimens,
      which are widely used in tobacco smoke research, may not produce realistic smoke
      aerosols.

PMID- 16796539
TI  - Comparative analysis of different scintigraphic approaches to assess pulmonary
      ventilation.
AB  - A study was carried out to investigate the predictive value of 81-metastable
      krypton (81mKr) distribution, high-size 99-metastable-technetium (99mTc) aerosol
      deposition and low-size 99mTc aerosol (Technegas) deposition on the pulmonary
      ventilation evaluated by 133-xenon (133Xe) lung scintigraphy, and to assess the
      correlation between the 81mKr distribution, the 99mTc aerosols deposition, and
      the respiratory parameters of patients with chronic obstructive pulmonary disease
      (COPD). Twenty COPD patients were included. The 81mKr, 133Xe, and 99mTc aerosol
      lung scintigraphies were successively carried out. The 81mKr distribution and
      99mTc deposition were compared to the 133Xe distribution at equilibrium and to
      the 133Xe clearance. Sensitivity, specificity, positive predictive value (PPV),
      and negative predictive value (NPV) of 81mKr and Technegas lung scintigraphies to
      detect alterations in ventilation revealed by 133Xe were defined. The 81mKr
      distribution and 99mTc deposition according to respiratory parameters were
      described using a principal component analysis. Compared to 133Xe distribution, a
      significantly higher distribution of 81mKr in the upper parts of the lungs in the
      more severe patients (p = 0.05), a significantly higher deposition of Technegas
      in the lower parts of the lungs (p = 0.0008), and a significantly higher
      deposition in the central parts of the high-size 99mTc aerosol were observed (p =
      0.0001). The PPV and the NPV were, respectively, 0.54 and 0.58 for 81mKr and 0.54
      and 0.55 for Technegas. There was a significant negative correlation between
      81mKr distribution and 133Xe clearance (p = 0.0001) between Technegas deposition
      and 133Xe clearance (p = 0.0007), and between 99mTc diethylene-triamino-penta
      acetate (DTPA) deposition and 133Xe clearance (p = 0.001). Both the 81mKr
      peripheral distribution and Technegas peripheral deposition correlated negatively
      with increased obstruction, as measured by forced expiratory volume in 1 sec
      (FEV1). Peripheral deposition of the high-size 99mTc aerosol deposition
      correlated with the inspiration/expiration time ratio. In conclusion, 81mKr and
      99mTc aerosols' lung scintigraphies do not reflect exactly the pulmonary
      ventilation as measured by 133Xe scintigraphy.

PMID- 16796540
TI  - Comparison of three valved holding chambers for the delivery of fluticasone
      propionate-HFA to an infant face model.
AB  - The purpose of this study was to compare three valved holding chambers (VHC) with
      facemasks attached. One VHC (AeroChamber Max[TM] with medium mask) was made with
      materials that dissipate surface electrostatic charge, and the others
      (OptiChamber Advantage and ProChamber[TM] with pediatric facemask) were made from
      non-conducting materials. The OptiChamber Advantage and ProChamber VHCs were each
      washed with an ionic detergent and drip dried before testing to minimize surface
      electrostatic charge. The AeroChamber Max VHCs were tested "out of the package"
      and also after wash, rinse, and drying. An infant face model incorporating an
      electrostatic filter in the oral cavity was connected to a breath simulator using
      a standard waveform for a small child. The fit of each VHC with facemask was
      demonstrated by agreement of inspiratory flow measurements between a
      pneumotachograph connected to the system with those set on the simulator. An HFA
      fluticasone propionate metered dose inhaler (MDI; 125 microg/dose) was inserted
      into the VHC, two actuations were delivered, and the filters were subsequently
      assayed using high-pressure liquid chromatography (HPLC). Testing and sample
      assay order was randomized, and HPLC assays were undertaken blinded. Drug
      delivery efficiency expressed as a percentage of the total dose of fluticasone
      propionate (250 microg) for the AeroChamber Max VHC "out-of-the-package" was
      22.0(0.7)% (mean [99% CI]) and 21.2(1.5)% when pre-washed/rinsed. Results for the
      pre-washed ProChamber and OptiChamber Advantage VHCs were 10.2(0.55)% and
      8.8(1.9)%, respectively. The more efficient delivery of medication via VHCs made
      from electrostatic charge dissipative materials should be considered when
      choosing doses for small children.

PMID- 16796541
TI  - A dry powder inhaler with reduced mouth-throat deposition.
AB  - A novel, compact, and highly efficient dry powder inhaler (DPI) with low mouth
      throat deposition is described. The performance of this DPI was evaluated by
      measuring both (1) the total aerosol deposition in and distal to an idealized
      mouth-throat cast and (2) the fine particle fraction (FPF) using a standard Mark
      II Anderson impactor. Ultraviolet (UV) spectroscopy techniques were used in the
      aerosol deposition measurements. Two inhalation aerosol powders, namely
      budesonide (extracted from a Pulmicort/Turbuhaler multi-dose device, 200
      microg/dose) and ciprofloxacin + lipid + lactose (in-house), were dispersed by
      the DPI at a steady inhalation flow rate of 60 L/min. The newly developed DPI had
      a total aerosol delivery distal to the mouth-throat cast of 50.5% +/- 3.04% and
      69.7% +/- 1.5% for the budesonide and ciprofloxacin + lipid + lactose aerosols,
      respectively. This is a significant improvement over the Turbuhaler original
      device delivery of 34.5% +/- 5.2%, particularly considering that in vitro mouth
      throat deposition dropped from 27.5% +/- 5.4% with the budesonide Turbuhaler to
      11.0% +/- 3.5% with the present inhaler. The different lung deliveries from the
      same inhaler for the two formulations above also confirm that the overall
      performance of an inhaler is optimizable via powder formulations.

PMID- 16796542
TI  - Factors influencing the in vitro deposition of tobramycin aerosol: a comparison
      of an ultrasonic nebulizer and a high-frequency vibrating mesh nebulizer.
AB  - The aim of the study was to elaborate recommendations for inhalation during
      mechanical ventilation that could optimize delivery. Delivery of aerosols in
      vitro from nebulizers during mechanical ventilation is dependent on the
      dimensions of the ventilator circuit, the nebulizer type, and the ventilator
      settings. A review of the literature shows that some ventilator settings have a
      larger influence on the amount of aerosol delivered than others. It has been
      shown in an in vitro model that the factors influencing delivered aerosol are the
      ventilator flow rate, the diameter of the endotracheal tube, and the time spent
      in inspiration (all p < 0.05). Two different nebulizer types were used in the
      study: an ultrasonic nebulizer (SUN 345) and a high-frequency vibrating mesh
      nebulizer (Aeroneb Pro). No difference in the amount delivered was seen with
      different nebulizer types (p = 0.215). For optimizing the amount delivered, the
      largest possible flow, endotracheal tube, and time spent in inspiration should be
      used.

PMID- 16796543
TI  - Isotonic and hypertonic saline droplet deposition in a human upper airway model.
AB  - The evaporative and hygroscopic effects and deposition of isotonic and hypertonic
      saline droplets have been simulated from the mouth to the first four generations
      of the tracheobronchial tree under laminar-transitional-turbulent inspiratory
      flow conditions. Specifically, the local water vapor transport, droplet
      evaporation rate, and deposition fractions are analyzed. The effects of
      inhalation flow rates, thermodynamic air properties and NaCl-droplet
      concentrations of interest are discussed as well. The validated computer
      simulation results indicate that the increase of NaCl-solute concentration,
      increase of inlet relative humidity, or decrease of inlet air temperature may
      reduce water evaporation and increase water condensation at saline droplet
      surfaces, resulting in higher droplet depositions due to the increasing particle
      diameter and density. However, solute concentrations below 10% may not have a
      very pronounced effect on droplet deposition in the human upper airways.

PMID- 16796544
TI  - Comparison of lung deposition of amikacin by intrapulmonary percussive
      ventilation and jet nebulization by urinary monitoring.
AB  - The intrapulmonary percussive ventilation (IPV), frequently coupled with a
      nebulizer, is increasingly used as a physiotherapy technique; however, its
      physiologic and clinical values have been poorly studied. The aim of this study
      was to compare lung deposition of amikacin by the nebulizer of the IPV device
      (Percussionaire; Percussionaire Corporation; Sandpoint, ID) and that of standard
      jet nebulization (SST; SideStream; Medic-Aid; West Sussex, UK). Amikacin was
      nebulized with both devices in a group of five healthy subjects during
      spontaneous breathing. The deposition of amikacin was measured by urinary
      monitoring. Drug output of both devices was measured. Respiratory frequency (RF)
      was significantly lower when comparing the IPV device with SST (8.2 +/- 1.6
      breaths/min vs. 12.6 +/- 2.5 breaths/min, p < 0.05). The total daily amount of
      amikacin excreted in the urine was significantly lower with IPV than with SST
      (0.8% initial dose vs. 5.6% initial dose, p < 0.001). Elimination halflife was
      identical with both devices. Drug output was lower with IPV than with SST. The
      amount of amikacin delivered to the lung is sixfold lower with IPV than with SST,
      although a lower respiratory frequency was adopted by the subjects with the IPV.
      Therefore, the IPV seems unfavorable for the nebulization of antibiotics.

PMID- 16796545
TI  - Steroid effects on mucociliary clearance in outpatient asthma.
AB  - Asthma, a chronic inflammatory condition of airways, responds to therapy with
      anti-inflammatory medications, for example, inhaled (ICS) and/or systemic (SS)
      corticosteroids. It is associated with impaired clearance of airway secretions.
      We studied effects of ICS and SS on mucociliary clearance (MC) in outpatient
      asthma through an in vivo, randomized, placebo-controlled single blind study with
      patients acting as their own control. Using a gamma camera and radiolabeled
      aerosol, we measured MC at baseline, after 4 days of nebulized treatment and
      after 5 days of oral prednisone. MC was expressed as percent of retained activity
      over time. Spirometry was performed before each MC study. Treatment with
      nebulized budesonide did not affect MC or forced expiratory volume at 1 sec
      (FEV1). Treatment with SS was associated with a significant improvement in MC at
      24 h (baseline, 41 +/- 6; post-SS, 36 +/- 5; p = 0.04). Post hoc analysis
      revealed that MC changed only in those patients with significant changes in
      deposition (specific Central-to-Peripheral ratio C/P--baseline, 1.57 +/- 0.16;
      post-SS, 1.73 +/- 0.21; n = 6; p = 0.05), suggesting that the changes in MC were
      not directly related to therapy. In outpatient asthma, MC is unaffected by 4-5
      days of anti-inflammatory therapy in spite of significant changes in FEV1.

PMID- 16796547
TI  - The distribution of genomic distance between random genomes.
AB  - We study the probability distribution of genomic distance d under the hypothesis
      of random gene order. We translate the random order assumption into a stochastic
      method for constructing the alternating color cycles in the decomposition of the
      bicolored breakpoint graph. For two random genomes of length n, we show that the
      expectation of n - d is O((1/2) log n).

PMID- 16796548
TI  - On the complexity of sparse exon assembly.
AB  - Gene structure prediction is one of the most important problems in computational
      molecular biology. It involves two steps: the first is finding the evidence
      (e.g., predicting splice sites) and the second is interpreting the evidence, that
      is, trying to determine the whole gene structure by assembling its pieces. In
      this paper, we suggest a combinatorial solution to the second step, which is also
      referred to as the "Exon Assembly Problem." We use a similarity-based approach
      that aims to produce a single gene structure based on similarities to a known
      homologous sequence. We target the sparse case, where filtering has been applied
      to the data, resulting in a set of O(n) candidate exon blocks. Our algorithm
      yields an O(n(2) square root of n) solution.

PMID- 16796550
TI  - A novel algorithm for non-bonded-list updating in molecular simulations.
AB  - Simulations of molecular systems typically handle interactions within non-bonded
      pairs. Generating and updating a list of these pairs can be the most time
      consuming part of energy calculations for large systems. Thus, efficient non
      bonded list processing can speed up the energy calculations significantly. While
      the asymptotic complexity of current algorithms (namely O(N), where N is the
      number of particles) is probably the lowest possible, a wide space for
      optimization is still left. This article offers a heuristic extension to the
      previously suggested grid based algorithms. We show that, when the average
      particle movements are slow, simulation time can be reduced considerably. The
      proposed algorithm has been implemented in the DistanceMatrix class of the
      molecular modeling package MESHI. MESHI is freely available at
      <www.cs.bgu.ac.il/~meshi>.

PMID- 16796549
TI  - A fast and symmetric DUST implementation to mask low-complexity DNA sequences.
AB  - The DUST module has been used within BLAST for many years to mask low-complexity
      sequences. In this paper, we present a new implementation of the DUST module that
      uses the same function to assign a complexity score to a sequence, but uses a
      different rule by which high-scoring sequences are masked. The new rule masks
      every nucleotide masked by the old rule and occasionally masks more. The new
      masking rule corrects two related deficiencies with the old rule. First, the new
      rule is symmetric with respect to reversing the sequence. Second, the new rule is
      not context sensitive; the decision to mask a subsequence does not depend on what
      sequences flank it. The new implementation is at least four times faster than the
      old on the human genome. We show that both the percentage of additional bases
      masked and the effect on MegaBLAST outputs are very small.

PMID- 16796551
TI  - Stochastic transcriptional regulatory systems with time delays: a mean-field
      approximation.
AB  - Modeling transcriptional regulation with time delays is an important problem of
      computational cell biology. In this paper, we propose a computational tool for
      studying transcriptional regulation in single cells based on a mean-field
      approximation method. The main idea is to replace the occurrence probabilities of
      the underlying transcriptional events by their mean values and use appropriately
      chosen additive noise terms to model statistical variations not accounted by this
      approximation. The proposed methodology allows us to characterize the transient
      and steady-state behavior of transcriptional regulation. Moreover, it provides a
      rather simple and computationally attractive tool for rapid statistical
      characterization of the dynamic behavior of a nonlinear transcriptional
      regulatory system with time delays.

PMID- 16796552
TI  - Grammatical representations of macromolecular structure.
AB  - Since the first application of context-free grammars to RNA secondary structures
      in 1988, many researchers have used both ad hoc and formal methods from
      computational linguistics to model RNA and protein structure. We show how nearly
      all of these methods are based on the same core principles and can be converted
      into equivalent approaches in the framework of tree-adjoining grammars and
      related formalisms. We also propose some new approaches that extend these core
      principles in novel ways.

PMID- 16796553
TI  - The identifiability of tree topology for phylogenetic models, including covarion
      and mixture models.
AB  - For a model of molecular evolution to be useful for phylogenetic inference, the
      topology of evolutionary trees must be identifiable. That is, from a joint
      distribution the model predicts, it must be possible to recover the tree
      parameter. We establish tree identifiability for a number of phylogenetic models,
      including a covarion model and a variety of mixture models with a limited number
      of classes. The proof is based on the introduction of a more general model,
      allowing more states at internal nodes of the tree than at leaves, and the study
      of the algebraic variety formed by the joint distributions to which it gives
      rise. Tree identifiability is first established for this general model through
      the use of certain phylogenetic invariants.

PMID- 16796554
TI  - Binary state pattern clustering: a digital paradigm for class and biomarker
      discovery in gene microarray studies of cancer.
AB  - Class and biomarker discovery continue to be among the preeminent goals in gene
      microarray studies of cancer. We have developed a new data mining technique,
      which we call Binary State Pattern Clustering (BSPC) that is specifically adapted
      for these purposes, with cancer and other categorical datasets. BSPC is capable
      of uncovering statistically significant sample subclasses and associated marker
      genes in a completely unsupervised manner. This is accomplished through the
      application of a digital paradigm, where the expression level of each potential
      marker gene is treated as being representative of its discrete functional state.
      Multiple genes that divide samples into states along the same boundaries form a
      kind of gene-cluster that has an associated sample-cluster. BSPC is an extremely
      fast deterministic algorithm that scales well to large datasets. Here we describe
      results of its application to three publicly available oligonucleotide microarray
      datasets. Using an alpha-level of 0.05, clusters reproducing many of the known
      sample classifications were identified along with associated biomarkers. In
      addition, a number of simulations were conducted using shuffled versions of each
      of the original datasets, noise-added datasets, as well as completely artificial
      datasets. The robustness of BSPC was compared to that of three other publicly
      available clustering methods: ISIS, CTWC and SAMBA. The simulations demonstrate
      BSPC's substantially greater noise tolerance and confirm the accuracy of our
      calculations of statistical significance.

PMID- 16796556
TI  - Large-scale prediction of protein structure and function from sequence.
AB  - The identification of novel drug targets from genomic data involves the large
      scale analysis of many protein sequences. Methods for automated structure and
      function prediction are an essential tool for this purpose. In this review we
      concentrate on the recent developments in the field of protein structure
      prediction and how these can be used to gain hints about the function of
      proteins. The current state-of-the-art is highlighted through recent community
      wide experiments aimed at comparing different approaches. For structure
      prediction this allows the identification of key improvements to increase the
      crucial sequence to structure alignment needed for accurate models. Function
      prediction is a rapidly maturing field that is still being benchmarked.
      Definitions for protein function are presented and available methods, mostly
      concentrating on functional site descriptors and structural motifs, presented.

PMID- 16796557
TI  - Structural biology and drug discovery.
AB  - In the past few years macromolecular crystallography has become a standard
      technique used by many pharmaceutical and biotechnology companies. This
      methodology offers details of protein-ligand interactions at levels of resolution
      virtually unmatched by any other technique, and this approach holds the promise
      of novel, more effective, safer and cheaper drugs. Although crystallography
      remains a laborious and rather expensive technique, remarkable advances in
      structure determination and structure based drug design (SBDD) have been made in
      recent years. This process has been aided by recent technological innovations
      such as high-throughput crystallization, high performance synchrotron beamlines,
      and new methods in structural bioinformatics and computational chemistry prompted
      by the structural genomics effort. As a consequence of the increased availability
      of structural data, the use of structure-based information has expanded from
      simple protein-ligand interaction analysis to include other aspects of the drug
      discovery process like target selection and initial lead discovery that used to
      be almost the exclusive property of biology and chemistry. This review will cover
      recent examples to illustrate how macromolecular crystallography has evolved and
      how structural information is now being used in the different stages of the drug
      discovery process. Advantages and shortcomings of the methodology will also be
      discussed.

PMID- 16796558
TI  - Molecular descriptors and methods for ligand based virtual high throughput
      screening in drug discovery.
AB  - The aim of virtual high throughput screening is the identification of
      biologically relevant molecules amongst either tangible or virtual (large)
      collections of compounds. Amongst the various virtual screening approaches, those
      that are ligand based are becoming very popular due to the possibility to screen
      millions of molecules in a timely way. Descriptors and methods are briefly
      introduced and reviewed with more emphasis for those approaches that are based on
      fingerprint descriptors and that seems to be more utilized during the drug
      discovery process.

PMID- 16796559
TI  - Recent developments of the chemistry development kit (CDK) - an open-source java
      library for chemo- and bioinformatics.
AB  - The Chemistry Development Kit (CDK) provides methods for common tasks in
      molecular informatics, including 2D and 3D rendering of chemical structures, I/O
      routines, SMILES parsing and generation, ring searches, isomorphism checking,
      structure diagram generation, etc. Implemented in Java, it is used both for
      server-side computational services, possibly equipped with a web interface, as
      well as for applications and client-side applets. This article introduces the
      CDK's new QSAR capabilities and the recently introduced interface to statistical
      software.

PMID- 16796560
TI  - Development, validation, and applications of anisotropic polarizable molecular
      mechanics to study ligand and drug-receptor interactions.
AB  - A correct representation of intermolecular interaction energies is necessary for
      reliable drug-receptor docking studies. While ab initio quantum chemistry with
      extended basis sets is the most accurate tool for that purpose, its use is
      precluded for very large molecular complexes. This constitutes the incentive for
      the development of accurate molecular mechanics potentials, in which the first
      order electrostatic, and the second-order polarization energy contributions, are
      of essential importance. In this paper, we review the most important steps in the
      development of anisotropic, polarizable molecular mechanics (APMM) procedures.
      Among these, we illustrate validation tests of the ab initio-grounded,
      polarizable molecular mechanics potential, SIBFA (Sum of Interactions Between
      Fragments Ab initio computed). These are done by comparisons with parallel
      quantum-chemical (QC) results on representative multiply hydrogen-bonded
      complexes and polycoordinated complexes of one, or of two, divalent metal
      cations. For both kinds of complexes, the need to reproduce the non-additivity of
      the QC interaction energies is emphasized. One difficulty arises upon handling
      flexible molecules, due to the need to account simultaneously and consistently
      for the onset of inter- and intra-molecular polarization and charge-transfer
      effects. A new approach in the context of SIBFA was recently developed towards
      this aim, and tested in two cases of conformation-dependent cation-ligand
      interaction energies. The first relates to the complexes formed between the
      mecapto-carboxamide anion, an essential building-block of several Zn
      metalloenzyme inhibitors, and Zn(II). The second relates to the complexes of the
      tetra-anionic pyrophosphate anion, a key building-block of ATP and GTP, with one
      or two divalent Zn(II) cations used as a probe. In the domain of applications,
      two recent studies are then presented. The first is the docking of the captopril
      drug to the active site of the binuclear Zn(II)- beta-lactamase enzyme. The
      second is the complex of a non-hydrolyzable analog of ATP with the active site of
      a binuclear Mg(II)-dependent kinase. An extension to an open-shell cation,
      Cu(II), is finally presented. The encouraging results presented in this review
      show that APMM procedures could be used in large-scale studies of ligand and drug
      receptor interactions.

PMID- 16796561
TI  - In silico approaches towards the understanding of the structure-function
      relationships in metabotropic glutamate receptors (mGluRs) and other family C
      GPRCs.
AB  - Family C of the superfamily of G-protein coupled receptors is a growing family of
      heptahelical receptors, which includes, among others, metabotropic glutamate
      receptors (mGluRs) and GABA(B) receptors. A common feature of all the members of
      family C is a structural architecture much more complex than any other GPCRs.
      Computational studies, including homology modeling, pharmacophore definitions and
      molecular dynamics simulations have constantly flanked experimental approaches in
      the understanding of the receptor functioning. The present review will discuss
      the evolution of our perception in family C GPCRs structure and function as
      emerged from the critical comparison of in silico methods with molecular biology
      and crystallographic experiments.

PMID- 16796562
TI  - Ligand-based homology modeling as attractive tool to inspect GPCR structural
      plasticity.
AB  - G protein-coupled receptors (GPCRs) represent the largest family known of signal
      transducing molecules. They convey signals for light and many extracellular
      regulatory molecules. GPCRs have been found to be dysfunctional/dysregulated in a
      growing number of human diseases and they have been estimated to be the targets
      of more than 40% of the drugs used in clinical medicine today. The crystal
      structure of rhodopsin provides the first three-dimensional GPCR information,
      which now supports homology modeling studies and structure-based drug design
      approaches. Here, we review our recent work on adenosine receptors, a family of
      GPCRs and, in particular, on A(3) adenosine receptor subtype antagonists. We will
      focus on an alternative approach to computationally explore the multi
      conformational space of the antagonist-like state of the human A(3) receptor. We
      define ligand-based homology modeling as new approach to simulate the
      reorganization of the receptor induced by the ligand binding. The success of this
      approach is due to the synergic interaction between theory and experiment.

PMID- 16796563
TI  - Conformational transitions induced in heparin octasaccharides by binding with
      antithrombin III.
AB  - The present study deals with the conformation in solution of two heparin
      octasaccharides containing the pentasaccharide sequence GlcN(NAc,6S)-GlcA
      GlcN(NS,3,6S)-IdoA(2S)-GlcN(NS,6S) [AGA*IA; where GlcN(NAc,6S) is N-acetylated, 6
      O-sulfated alpha-D-glucosamine, GlcN(NS,3,6S) is N,3,6-O-trisulfated alpha-D
      glucosamine and IdoA(2S) is 2-O-sulfated IdoA (alpha-L-iduronic acid)] located at
      different positions in the heparin chain and focuses on establishing geometries
      of IdoA residues (IdoA(2S) and IdoA) both inside and outside the AGA*IA sequence.
      AGA*IA constitutes the active site for AT (antithrombin) and is essential for the
      expression of high anticoagulant and antithrombotic activities. Analysis of NMR
      parameters [NOEs (nuclear Overhauser effects), transferred NOEs and coupling
      constants] for the two octasaccharides indicated that between the 1C4 and 2S0
      conformations present in dynamic equilibrium in the free state for the IdoA(2S)
      residue within AGA*IA, AT selects the 2S0 form, as previously shown [Hricovini,
      Guerrini, Bisio, Torri, Petitou and Casu (2001) Biochem. J. 359, 265-272].
      Notably, the 2S0 conformation is also adopted by the non-sulfated IdoA residue
      preceding AGA*IA that, in the absence of AT, adopts predominantly the 1C4 form.
      These results further support the concept that heparin-binding proteins influence
      the conformational equilibrium of iduronic acid residues that are directly or
      indirectly involved in binding and select one of their equi-energetic
      conformations for best fitting in the complex. The complete reversal of an
      iduronic acid conformation preferred in the free state is also demonstrated for
      the first time. Preliminary docking studies provided information on the
      octasaccharide binding location agreeing most closely with the experimental data.
      These results suggest a possible biological role for the non-sulfated IdoA
      residue preceding AGA*IA, previously thought not to influence the AT-binding
      properties of the pentasaccharide. Thus, for each AT binding sequence longer than
      AGA*IA, the interactions with the protein could differ and give to each heparin
      fragment a specific biological response.

PMID- 16796564
TI  - Optimal eradication: when to stop looking for an invasive plant.
AB  - The notion of being sure that you have completely eradicated an invasive species
      is fanciful because of imperfect detection and persistent seed banks. Eradication
      is commonly declared either on an ad hoc basis, on notions of seed bank
      longevity, or on setting arbitrary thresholds of 1% or 5% confidence that the
      species is not present. Rather than declaring eradication at some arbitrary level
      of confidence, we take an economic approach in which we stop looking when the
      expected costs outweigh the expected benefits. We develop theory that determines
      the number of years of absent surveys required to minimize the net expected cost.
      Given detection of a species is imperfect, the optimal stopping time is a trade
      off between the cost of continued surveying and the cost of escape and damage if
      eradication is declared too soon. A simple rule of thumb compares well to the
      exact optimal solution using stochastic dynamic programming. Application of the
      approach to the eradication programme of Helenium amarum reveals that the actual
      stopping time was a precautionary one given the ranges for each parameter.

PMID- 16796565
TI  - Do biotic interactions shape both sides of the humped-back model of species
      richness in plant communities?
AB  - A humped-back relationship between species richness and community biomass has
      frequently been observed in plant communities, at both local and regional scales,
      although often improperly called a productivity-diversity relationship.
      Explanations for this relationship have emphasized the role of competitive
      exclusion, probably because at the time when the relationship was first examined,
      competition was considered to be the significant biotic filter structuring plant
      communities. However, over the last 15 years there has been a renewed interest in
      facilitation and this research has shown a clear link between the role of
      facilitation in structuring communities and both community biomass and the
      severity of the environment. Although facilitation may enlarge the realized niche
      of species and increase community richness in stressful environments, there has
      only been one previous attempt to revisit the humped-back model of species
      richness and to include facilitative processes. However, to date, no model has
      explored whether biotic interactions can potentially shape both sides of the
      humped-back model for species richness commonly detected in plant communities.
      Here, we propose a revision of Grime's original model that incorporates a new
      understanding of the role of facilitative interactions in plant communities. In
      this revised model, facilitation promotes diversity at medium to high
      environmental severity levels, by expanding the realized niche of stress
      intolerant competitive species into harsh physical conditions. However, when
      environmental conditions become extremely severe the positive effects of the
      benefactors wane (as supported by recent research on facilitative interactions in
      extremely severe environments) and diversity is reduced. Conversely, with
      decreasing stress along the biomass gradient, facilitation decreases because
      stress-intolerant species become able to exist away from the canopy of the stress
      tolerant species (as proposed by facilitation theory). At the same time
      competition increases for stress-tolerant species, reducing diversity in the most
      benign conditions (as proposed by models of competition theory). In this way our
      inclusion of facilitation into the classic model of plant species diversity and
      community biomass generates a more powerful and richer predictive framework for
      understanding the role of plant interactions in changing diversity. We then use
      our revised model to explain both the observed discrepancies between natural
      patterns of species richness and community biomass and the results of
      experimental studies of the impact of biodiversity on the productivity of
      herbaceous communities. It is clear that explicit consideration of concurrent
      changes in stress-tolerant and competitive species enhances our capacity to
      explain and interpret patterns in plant community diversity with respect to
      environmental severity.

PMID- 16796566
TI  - Threshold elemental ratios of carbon and phosphorus in aquatic consumers.
AB  - Inadequate supply of one or more mineral elements can slow the growth of animal
      consumers and alter their physiology, life history and behaviour. A key concept
      for understanding nutrient deficiency in animals is the threshold elemental ratio
      (TER), at which growth limitation switches from one element to another. We used a
      stoichiometric model that coupled animal bioenergetics and body elemental
      composition to estimate TER of carbon and phosphorus (TER(C:P)) for 41 aquatic
      consumer taxa. We found a wide range in TER(C:P) (77-3086, ratio by atoms), which
      was generated by interspecific differences in body C : P ratios and gross growth
      efficiencies of C. TER(C:P) also varied among aquatic invertebrates having
      different feeding strategies, such that detritivores had significantly higher
      threshold ratios than grazers and predators. The higher TER(C:P) in detritivores
      resulted not only from lower gross growth efficiencies of carbon but also
      reflected lower body P content in these consumers. Supporting previous
      stoichiometric theory, we found TER(C:P) to be negatively correlated with the
      maximum growth rate of invertebrate consumers. By coupling bioenergetics and
      stoichiometry, this analysis revealed strong linkages among the physiology,
      ecology and evolution of nutritional demands for animal growth.

PMID- 16796567
TI  - Herbivore impact on grassland plant diversity depends on habitat productivity and
      herbivore size.
AB  - Mammalian herbivores can have pronounced effects on plant diversity but are
      currently declining in many productive ecosystems through direct extirpation,
      habitat loss and fragmentation, while being simultaneously introduced as
      livestock in other, often unproductive, ecosystems that lacked such species
      during recent evolutionary times. The biodiversity consequences of these changes
      are still poorly understood. We experimentally separated the effects of primary
      productivity and herbivores of different body size on plant species richness
      across a 10-fold productivity gradient using a 7-year field experiment at seven
      grassland sites in North America and Europe. We show that assemblages including
      large herbivores increased plant diversity at higher productivity but decreased
      diversity at low productivity, while small herbivores did not have consistent
      effects along the productivity gradient. The recognition of these large-scale,
      cross-site patterns in herbivore effects is important for the development of
      appropriate biodiversity conservation strategies.

PMID- 16796568
TI  - Predator biodiversity strengthens herbivore suppression.
AB  - Species diversity at lower trophic levels generally improves ecosystem
      functioning. However, the impact of greater predator diversity on herbivore
      regulation is uncertain because predator species both compete with and prey on
      each other. In a large-scale field experiment we examined the relationship
      between predator species diversity and the suppression of two herbivores, green
      peach and cabbage aphids, on collard plants. We show that, for both aphid
      species, the strength of herbivore suppression increased with higher predator
      biodiversity. Greater resource exploitation by predators in diverse communities
      generally led to improved predator survivorship and reproduction. Herbivore
      population size was negatively correlated with plant biomass, providing evidence
      that greater aphid suppression leads to improved plant growth. Our study suggests
      a harmonious relationship between predator conservation and herbivore control,
      and a relatively weak role for predator interference, within this community.

PMID- 16796569
TI  - Propagule vs. niche limitation: untangling the mechanisms behind plant species'
      distributions.
AB  - Distinguishing the roles of propagule limitation and niche requirements in
      controlling plant species distributions is important for understanding community
      structure, invasion, and restoration. We used species distribution models based
      on plant and environmental survey data to assess the strength of species'
      affinities for particular environmental conditions. We hypothesized that species
      with statistically detectable environmental requirements were primarily niche
      limited, while species with weak habitat affinities were primarily propagule
      limited. We tested this hypothesis via a seeding experiment in which we compared
      species' reproductive fitness in occupied and unoccupied sites. Species that
      appeared to be niche-limited based on distribution models had lower fitness when
      planted in unoccupied sites, while species that models suggested were propagule
      limited had equivalent fitness when planted in occupied and unoccupied sites. Our
      results demonstrate that within a single community, both species limited
      primarily by niche availability or primarily by propagule availability can be
      identified using observational data.

PMID- 16796570
TI  - Taxa-area relationships for microbes: the unsampled and the unseen.
AB  - The recent observation of a power-law relationship, S proportional A(z), between
      number of taxa, S, and area, A, for microbial eukaryotes and bacteria suggests
      that this is one of the few generic relationships in ecology, applicable to
      plants, animals and microbes. However, the rate of increase in the number of
      species with area varies from approximately the fourth (z = 0.26) to as little as
      the 50th root (z = 0.0019) in microbes. This is an enormous range for which no
      quantitative explanation has been proffered. We show by sampling from synthetic
      populations that the disparity between sample and community sizes in microbial
      community surveys means z can be considerably underestimated and accrual of rare
      taxa with increasing area will not be detectable. Significant microbial taxa-area
      relationships will only be observed when changes in community structure within
      samples correlate with area. Thus, the very low z values observed recently cannot
      be used as the sole evidence in support of any particular community theory of
      community assembly. More generally, this suggests that our search for patterns
      and laws in the microbial world will be profoundly influenced and, potentially
      distorted by the sample sizes that are typical of microbial community surveys.

PMID- 16796571
TI  - Priming of indirect defences.
AB  - Leaf damage induces in many plant species the secretion of extrafloral nectar
      (EFN) and/or the release of specific odours (volatile organic compounds, VOCs).
      Both traits attract carnivorous arthropods and function as indirect plant
      defences by increasing the predation pressure on attacking herbivores. We have
      conducted field experiments in Mexico and found that plants that had been exposed
      to VOCs thereafter responded to subsequent leaf damage with an increased EFN
      secretion. VOCs 'primed' the plants to respond more efficiently once they were
      attacked themselves. Such priming effects are well known for induced resistance
      to pathogens, yet this is the first description of VOCs priming EFN secretion, a
      taxonomically widespread anti-herbivore defence. Plants can use chemical signals
      in their environment to assess the risk of herbivory and make use of this
      information to adjust their own defensive strategy accordingly.

PMID- 16796572
TI  - Ecological persistence interrupted in Caribbean coral reefs.
AB  - The recent mass mortality of Caribbean reef corals dramatically altered reef
      community structure and begs the question of the past stability and persistence
      of coral assemblages before human disturbance began. We report within habitat
      stability in coral community composition in the Pleistocene fossil record of
      Barbados for at least 95,000 years despite marked variability in global sea level
      and climate. Results were consistent for surveys of both common and rare taxa.
      Comparison of Pleistocene and modern community structure shows that Recent human
      impacts have changed coral community structure in ways not observed in the
      preceding 220,000 years.

PMID- 16796573
TI  - Distributions of exotic plants in eastern Asia and North America.
AB  - Although some plant traits have been linked to invasion success, the possible
      effects of regional factors, such as diversity, habitat suitability, and human
      activity are not well understood. Each of these mechanisms predicts a different
      pattern of distribution at the regional scale. Thus, where climate and soils are
      similar, predictions based on regional hypotheses for invasion success can be
      tested by comparisons of distributions in the source and receiving regions. Here,
      we analyse the native and alien geographic ranges of all 1567 plant species that
      have been introduced between eastern Asia and North America or have been
      introduced to both regions from elsewhere. The results reveal correlations
      between the spread of exotics and both the native species richness and
      transportation networks of recipient regions. This suggests that both species
      interactions and human-aided dispersal influence exotic distributions, although
      further work on the relative importance of these processes is needed.

PMID- 16796574
TI  - Indirect effects of algae on coral: algae-mediated, microbe-induced coral
      mortality.
AB  - Declines in coral cover are generally associated with increases in the abundance
      of fleshy algae. In many cases, it remains unclear whether algae are responsible,
      directly or indirectly, for coral death or whether they simply settle on dead
      coral surfaces. Here, we show that algae can indirectly cause coral mortality by
      enhancing microbial activity via the release of dissolved compounds. When coral
      and algae were placed in chambers together but separated by a 0.02 mum filter,
      corals suffered 100% mortality. With the addition of the broad-spectrum
      antibiotic ampicillin, mortality was completely prevented. Physiological
      measurements showed complementary patterns of increasing coral stress with
      proximity to algae. Our results suggest that as human impacts increase and algae
      become more abundant on reefs a positive feedback loop may be created whereby
      compounds released by algae enhance microbial activity on live coral surfaces
      causing mortality of corals and further algal growth.

PMID- 16796575
TI  - A simple persistence condition for structured populations.
AB  - The fundamental question in both basic and applied population biology of whether
      a species will increase in numbers is often investigated by finding the
      population growth rate as the largest eigenvalue of a deterministic matrix model.
      For a population classified only by age, and not stage or size, a simpler
      biologically interpretable condition can be used, namely whether R0, the mean
      number of offspring per newborn, is greater than one. However, for the many
      populations not easily described using only age classes, stage-structured models
      must be used for which there is currently no quantity like R0. We determine
      analogous quantities that must be greater than one for persistence of a general
      structured population model that have a similar useful biological interpretation.
      Our approach can be used immediately to determine the magnitude of changes and
      interactions that would either allow population persistence or would ensure
      control of an undesirable species.

PMID- 16796576
TI  - Ecotypic variation in the context of global climate change: revisiting the rules.
AB  - Patterns of ecotypic variation constitute some of the few 'rules' known to modern
      biology. Here, we examine several well-known ecogeographical rules, especially
      those pertaining to body size in contemporary, historical and fossil taxa. We
      review the evidence showing that rules of geographical variation in response to
      variation in the local environment can also apply to morphological changes
      through time in response to climate change. These rules hold at various time
      scales, ranging from contemporary to geological time scales. Patterns of body
      size variation in response to climate change at the individual species level may
      also be detected at the community level. The patterns underlying ecotypic
      variation are complex and highly context-dependent, reducing the 'predictive
      power' of ecogeographical rules. This is especially true when considering the
      increasing impact of human activities on the environment. Nonetheless,
      ecogeographical rules may help interpret the likely influences of anthropogenic
      climate change on ecosystems. Global climate change has already influenced the
      body size of several contemporary species, and will likely have an even greater
      impact on animal communities in the future. For this reason, we highlight and
      emphasise the importance of museum specimens and the continued need for
      documenting the earth's biological diversity.

PMID- 16796577
TI  - The influence of biotic interactions on soil biodiversity.
AB  - Belowground communities usually support a much greater diversity of organisms
      than do corresponding aboveground ones, and while the factors that regulate their
      diversity are far less well understood, a growing number of recent studies have
      presented data relevant to understanding how these factors operate. This review
      considers how biotic factors influence community diversity within major groups of
      soil organisms across a broad spectrum of spatial scales, and addresses the
      mechanisms involved. At the most local scale, soil biodiversity may potentially
      be affected by interactions within trophic levels or by direct trophic
      interactions. Within the soil, larger bodied invertebrates can also influence
      diversity of smaller sized organisms by promoting dispersal and through
      modification of the soil habitat. At larger scales, individual plant species
      effects, vegetation composition, plant species diversity, mixing of plant litter
      types, and aboveground trophic interactions, all impact on soil biodiversity.
      Further, at the landscape scale, soil diversity also responds to vegetation
      change and succession. This review also considers how a conceptual understanding
      of the biotic drivers of soil biodiversity may assist our knowledge of key topics
      in community and ecosystem ecology, such as aboveground-belowground interactions,
      and the relationship between biodiversity and ecosystem functioning. It is
      concluded that an improved understanding of what drives the diversity of life in
      the soil, incorporated within appropriate conceptual frameworks, should
      significantly aid our understanding of the structure and functioning of
      terrestrial communities.

PMID- 16796578
TI  - Interactions between resource availability and enemy release in plant invasion.
AB  - Understanding why some exotic species become invasive is essential to controlling
      their populations. This review discusses the possibility that two mechanisms of
      invasion, release from natural enemies and increased resource availability, may
      interact. When plants invade new continents, they leave many herbivores and
      pathogens behind. Species most regulated by enemies in their native range have
      the most potential for enemy release, and enemy regulation may be strongest for
      high-resource species. High resource availability is associated with low defence
      investment, high nutritional value, high enemy damage and consequently strong
      enemy regulation. Therefore, invasive plant species adapted to high resource
      availability may also gain most from enemy release. Strong release of high
      resource species would predict that: (i) both enemy release and resources may
      underlie plant invasion, leading to potential interactions among control
      measures; (ii) increases in resource availability due to disturbance or
      eutrophication may increase the advantage of exotic over native species; (iii)
      exotic species will tend to have high-resource traits relative to coexisting
      native species; and (iv) although high-resource plants may experience strong
      enemy release in ecological time, well-defended low-resource plants may have
      stronger evolutionary responses to the absence of enemies.

PMID- 16796579
TI  - EFNS guideline on the treatment of cerebral venous and sinus thrombosis.
AB  - Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which
      accounts for <1% of all strokes. Diagnosis is still frequently overlooked or
      delayed due to the wide spectrum of clinical symptoms and the often subacute or
      lingering onset. Current therapeutic measures which are used in clinical practice
      include the use of anticoagulants such as dose-adjusted intravenous heparin or
      body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of
      thrombolysis, and symptomatic therapy including control of seizures and elevated
      intracranial pressure. We searched MEDLINE (National Library of Medicine), the
      Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library
      to review the strength of evidence to support these interventions and the
      preparation of recommendations on the therapy of CVST based on the best available
      evidence. Review articles and book chapters were also included. Recommendations
      were reached by consensus. Where there was a lack of evidence, but consensus was
      clear we stated our opinion as good practice points. Patients with CVST without
      contraindications for anticoagulation should be treated either with body weight
      adjusted subcutaneous LMWH or dose-adjusted intravenous heparin (good practice
      point). Concomitant intracranial haemorrhage related to CVST is not a
      contraindication for heparin therapy. The optimal duration of oral
      anticoagulation after the acute phase is unclear. Oral anticoagulation may be
      given for 3 months if CVST was secondary to a transient risk factor, for 6-12
      months in patients with idiopathic CVST and in those with 'mild' hereditary
      thrombophilia. Indefinite anticoagulation (AC) should be considered in patients
      with two or more episodes of CVST and in those with one episode of CVST and
      'severe' hereditary thrombophilia (good practice point). There is insufficient
      evidence to support the use of either systemic or local thrombolysis in patients
      with CVST. If patients deteriorate despite adequate anticoagulation and other
      causes of deterioration have been ruled out, thrombolysis may be a therapeutic
      option in selected cases, possibly in those without intracranial haemorrhage
      (good practice point). There are no controlled data about the risks and benefits
      of certain therapeutic measures to reduce an elevated intracranial pressure (with
      brain displacement) in patients with severe CVST. Antioedema treatment (including
      hyperventilation, osmotic diuretics and craniectomy) should be used as life
      saving interventions (good practice point).

PMID- 16796580
TI  - EFNS guideline on the drug treatment of migraine - report of an EFNS task force.
AB  - Migraine is one of the most frequent disabling neurological conditions with a
      major impact on the patients' quality of life. To give evidence-based or expert
      recommendations for the different drug treatment procedures of the different
      migraine syndromes based on a literature search and an consensus in an expert
      panel. All available medical reference systems were screened for all kinds of
      clinical studies on migraine with and without aura and on migraine-like
      syndromes. The findings in these studies were evaluated according to the
      recommendations of the EFNS resulting in level A,B, or C recommendations and good
      practice points. For the acute treatment of migraine attacks, oral non-steroidal
      anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration
      should follow the concept of stratified treatment. Before intake of NSAIDs and
      triptans, oral metoclopramide or domperidon is recommended. In very severe
      attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs
      of first choice. A status migrainosus can probably be treated by steroids. For
      the prophylaxis of migraine, betablockers (propranolol and metoprolol),
      flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of
      second choice for migraine prophylaxis are amitriptyline, naproxen, petasites,
      and bisoprolol.

PMID- 16796581
TI  - The association between apolipoprotein E and multiple sclerosis.
AB  - The article is a complete literature study that investigates the association
      between apolipoprotein E (Apo E) and multiple sclerosis (MS). Apo E is an
      important factor in transport, uptake, and redistribution of cholesterol, which
      is significant to remodelling and repair of nerve tissue. Apo E is involved in
      neurodegenerative diseases and the most well known association is between Apo
      epsilon4 and Alzheimer's disease. Only one study found that homozygosity for Apo
      epsilon4 does cause an increased risk of developing MS. No results indicate that
      heterozygosity for Apo epsilon4 causes a greater risk of developing MS. No
      association between the Apo epsilon4 allele and MS subgroups, age of onset, and
      gender has been found. The association between Apo epsilon4 and relapse rate is
      contradictory. Most results confirm the hypothesis about an association between
      the Apo epsilon4 allele and increased disease progression. Two longitudinal
      studies found an association between Apo epsilon4 and increased disease
      progression. Half of the cross-sectional studies found the same association. Four
      of seven published studies examining the association between Apo epsilon4 and
      increased disease progression using magnetic resonance imaging (MRI) found a
      significant association. Apo epsilon4 appears to be a predisposing factor to a
      faster disease progression in MS.

PMID- 16796582
TI  - Stroke incidence and prevalence in Europe: a review of available data.
AB  - Reliable data on stroke incidence and prevalence are essential for calculating
      the burden of stroke and the planning of prevention and treatment of stroke
      patients. In the current study we have reviewed the published data from EU
      countries, Iceland, Norway, and Switzerland, and provide WHO estimates for stroke
      incidence and prevalence in these countries. Studies on stroke epidemiology
      published in peer-reviewed journals during the past 10 years were identified
      using Medline/PubMed searches, and reviewed using the structure of WHO's stroke
      component of the WHO InfoBase. WHO estimates for stroke incidence and prevalence
      for each country were calculated from routine mortality statistics. Rates from
      studies that met the 'ideal' criteria were compared with WHO's estimates. Forty
      four incidence studies and 12 prevalence studies were identified. There were
      several methodological differences that hampered comparisons of data. WHO stroke
      estimates were in good agreement with results from 'ideal' stroke population
      studies. According to the WHO estimates the number of stroke events in these
      selected countries is likely to increase from 1.1 million per year in 2000 to
      more than 1.5 million per year in 2025 solely because of the demographic changes.
      Until better and more stroke studies are available, the WHO stroke estimates may
      provide the best data for understanding the stroke burden in countries where no
      stroke data currently exists. A standardized protocol for stroke surveillance is
      recommended.

PMID- 16796583
TI  - Subcortical deficit pattern after brain abscess: a neuropsychological study.
AB  - The consequences of brain abscess (BA) on cognition and behaviour have never been
      examined in detail. The aim of this study was to determine the long-term
      cognitive deficits of patients who suffered a BA and to estimate its effect on
      the quality of life. Twenty patients were included in the study. Follow up with
      neuropsychological and behavioural tests was performed 6 months to 42 years after
      BA (mean 10.4 +/- 11.9). Cognitive deficits were defined as a test score of 2 or
      more standard deviations below controls' mean in those tasks which revealed a
      significant group deficit. Compared with healthy age, sex and education-matched
      controls, 13 of 20 patients (65%) exhibited neuropsychological deficits in some
      cognitive tasks. Ten of those patients (50%) were significantly impaired in < or
      =2 cognition domains, whilst the remaining three patients (15%) showed three to
      five impaired domains. No correlation was found between neuropsychological
      impairments and patients' age, sex, initial neurological symptoms, size and
      localization of BA, or secondary epileptic seizures. Reduction in quality of life
      was found in five patients (25%). BA may cause long lasting cognitive deficits.
      Despite the focal character of the lesion, long-term sequelae follow a more
      diffuse subcortical deficit pattern.

PMID- 16796584
TI  - Oral fumaric acid esters for the treatment of active multiple sclerosis: an open
      label, baseline-controlled pilot study.
AB  - An exploratory, prospective, open-label study of fumaric acid esters (FAE,
      Fumaderm(R)) was conducted in patients with relapsing-remitting multiple
      sclerosis (RRMS). The study consisted of the following four phases: 6-week
      baseline, 18-week treatment (target dose of 720 mg/day), 4-week washout, and a
      second 48-week treatment phase (target dose of 360 mg/day). Ten patients with an
      Expanded Disability Status Scale (EDSS) score of 2.0-6.0 and at least one
      gadolinium-enhancing (Gd+) lesion on T1-weighted magnetic resonance imaging (MRI)
      brain scans participated in the study. Safety was assessed by adverse events
      (AEs), blood chemistry/hematology, electrocardiogram, and urinalysis. The primary
      efficacy outcomes were number and volume of Gd+ lesions. Other clinical outcomes
      included EDSS score, ambulation index (AI), and nine-hole peg test (9-HPT).
      Effects of FAE on intracellular cytokine profiles, T-cell apoptosis, and soluble
      adhesion molecules were also assessed. Three patients withdrew during the first 3
      weeks of the study because of side effects, non-compliance, and follow-up loss.
      The most common AEs were gastrointestinal symptoms and flushing; all AEs were
      reported as mild and reversible. FAE produced significant reductions from
      baseline in number (P < 0.05) and volume (P < 0.01) of Gd+ lesions after 18 weeks
      of treatment; this effect persisted during the second treatment phase at half the
      target dose after the 4-week washout period. EDSS scores, AI, and 9-HPT remained
      stable or slightly improved from baseline in all patients. Measures of T-cell
      function demonstrated alterations in cytokines and circulating tumor necrosis
      factor. The results of this exploratory study suggest that further studies of FAE
      in patients with MS are warranted.

PMID- 16796585
TI  - Accuracy of bedside diagnosis versus Allen and Siriraj stroke scores in Turkish
      patients.
AB  - Computerized tomography and magnetic resonance imaging allow the accurate
      diagnosis in stroke and distinction of ischemic from hemorrhagic lesions.
      However, clinical diagnosis is still critical where neuroimaging techniques are
      not available, especially to establish first-aid measures in a stroke patient. In
      this prospective study of 300 patients with stroke, the diagnosis of ischemic and
      hemorrhagic strokes was made as an informal bedside diagnosis prior to
      neuroimaging. The accuracy of bedside diagnosis was also compared with the
      results of the Allen and Siriraj stroke scores. Then, the reliability of these
      scores and our informal bedside diagnosis, along with the final diagnosis, were
      compared with each other. Our informal bedside diagnosis was correct in 250 of
      the 300 patients (83.3%). The diagnostic sensitivity and positive predictive
      value (PPV) of bedside diagnosis for ischemic stroke were 87.8% and 86.0% and for
      intracerebral hemorrhage 75.7% and 78.5%, respectively. Sensitivity and PPV for
      every cut-off value of the Allen and Siriraj stroke scores were less than that of
      sensitivity and PPV of informal bedside diagnosis. When the receiver operating
      curves obtained from the Allen and Siriraj stroke scores were compared, the Allen
      stroke score was found to be a better predictor in the final diagnosis. Our data
      suggest that an informal bedside diagnoses is as good as diagnoses made on
      certain intracerebral hemorrhages and on certain ischemic strokes by the Siriraj
      and Allen stroke scores; when compared, the Allen score seems to be better than
      the Siriraj stroke score. Hence, the use of both scores is recommended in
      epidemiologic studies as a screening tool as suggested by previous studies
      employing other diagnostic tools in clinics.

PMID- 16796586
TI  - Parkinson's disease: the genetics of a heterogeneous disorder.
AB  - Since the first description of Parkinson's disease (PD) in 1817 attempts have
      been made to resolve the etiology of this common neurodegenerative disorder. In
      the last century the influence of heredity in PD was controversial. The
      identification of mutations in six genes responsible for Mendelian forms of PD;
      alpha-synuclein (SNCA), parkin (PRKN), ubiquitin C-terminal hydrolase L1 (UCH
      L1), oncogene DJ-1, PTEN-induced putative kinase 1 (PINK1), and most recently
      leucine-rich repeat kinase 2 (LRRK2), has confirmed the role of genetics in
      familial forms of the disease. The exact relationship of these familial disorders
      and related genes to the more common sporadic form is currently uncertain. The
      identification of LRRK2 mutations and the association of common variants in SNCA
      and UCH-L1 in apparently sporadic late-onset disease indicate these genes may be
      of greater importance than previously believed. The protein products of the six
      genes are involved in different pathways of neurodegeneration and have opened new
      avenues of research. This focused research will lead to the development of novel
      targeted therapies, which may revolutionize the treatment of PD for a substantial
      proportion of patients.

PMID- 16796587
TI  - A new de novo Notch3 mutation causing CADASIL.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) is one of the most common hereditary forms of
      stroke, and migraine with aura, mood disorders, or dementia, are also frequently
      found in these patients. Missense mutations in the Notch3 gene that create or
      destroy cysteine residues, have been found in most cases with a family history of
      the disease, although a few sporadic cases harbouring Notch3 mutations have also
      been described. Here, we describe a 44-year-old patient with clinical features of
      CADASIL who was a carrier of a new Notch3 mutation: cys128-->gly. Both parents
      were alive and healthy, and negative for the mutation. This case illustrates the
      interest of analysing the Notch3 gene in cases with clinical features of CADASIL,
      even in the absence of a family history of the disease.

PMID- 16796588
TI  - Increased GFAP and S100beta but not NSE serum levels after subarachnoid
      haemorrhage are associated with clinical severity.
AB  - Assessment of initial disease severity after subarachnoid haemorrhage (SAH)
      remains difficult. The objective of the study is to identify biochemical markers
      of brain damage in peripheral blood after SAH. Hospital admission S100beta, glial
      fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) serum levels
      were analysed in 67 patients with SAH. Disease severity was determined by using
      the World Federation of Neurological Surgeons (WFNS) scale and the Fisher CT
      (computerized tomography) grading scale. Mean astroglial serum concentrations
      taken at hospital admission were increased (S100beta 2.8-fold and GFAP 1.8-fold)
      compared with the upper limit of normal laboratory reference values (P95). The
      mean NSE concentration was within normal limits. S100beta (P < 0.001) and GFAP (P
      =0.011) but not NSE levels were higher in patients who were in coma at the time
      of hospital admission compared with patients who were not. Similarly S100beta and
      GFAP but not NSE serum levels increased with higher WFNS scores, raised
      intracranial pressure and higher CT Fisher grade scores. Concerning the location
      of the aneurysm, S100beta and GFAP serum levels were within normal limits after a
      perimesencephalic type of haemorrhage and significantly increased after
      aneurysmal type SAH. Increased glial (S100beta and GFAP) but not neuronal (NSE)
      protein serum concentrations are found after SAH, associated to the clinical
      severity of the initial injury.

PMID- 16796589
TI  - Estrogen receptor alpha and APOEepsilon4 polymorphisms interact to increase risk
      for sporadic AD in Italian females.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects
      both sexes, with a higher prevalence in women. Declining estrogen levels after
      menopause may render estrogen target neurons in the brain more susceptible to age
      or disease-related processes such as AD. To investigate the role of two single
      nucleotide polymorphisms in the first intron of the ER-alpha gene, denominated
      PvuII and XbaI, and their interaction with the known AD susceptibility gene APOE,
      we examined 131 patients with sporadic AD and 109 healthy control subjects. In
      multinomial logistic regression analysis, a significantly increased risk of
      sporadic AD because of interaction between the ER-alpha p allele and APOE
      epsilon4 allele was observed in women, taking subjects who had neither the p
      allele nor epsilon4 as reference [odds ratio (OR) 7.24; 95% CI, 2.22-23.60]. For
      women carrying the ER-alpha x allele together with APOE epsilon4, the risk of
      sporadic AD was similarly elevated (OR 8.33; 95% CI, 1.73-40.06). The data
      suggest that the p and x alleles of polymorphic ER-alpha gene interact
      synergistically with the APOE epsilon4 allele to increase the risk of AD in women
      but not in men in this Italian cohort.

PMID- 16796590
TI  - Foetal malformations and seizure control: 52 months data of the Australian
      Pregnancy Registry.
AB  - The Australian Pregnancy Registry, affiliated European Register of Antiepileptic
      drugs in Pregnancy (EURAP), recruits informed consenting women with epilepsy on
      treatment with antiepileptic drugs (AEDs), those untreated, and women on AEDs for
      other indications. Enrolment is considered prospective if it has occurred before
      presence or absence of major foetal malformations (FMs) are known, or
      retrospective, if they had occurred after the birth of infant or detection of
      major FM. Telephone Interviews are conducted to ascertain pregnancy outcome and
      collect data about seizures. To date 630 women have been enrolled, with 565 known
      pregnancy outcomes. Valproate (VPA) above 1100 mg/day was associated with a
      significantly higher incidence of FMs than other AEDs (P < 0.05). This was
      independent of other AED use or potentially confounding factors on multivariate
      analysis (OR = 7.3, P < 0.0001). Lamotrigine (LTG) monotherapy (n = 65), has so
      far been free of malformations. Although seizure control was not a primary
      outcome, we noted that more patients on LTG than on VPA required dose adjustments
      to control seizures. Data indicate an increased risk of FM in women taking VPA in
      doses >1100 mg/day compared with other AEDs. The choice of AED for pregnant women
      with epilepsy requires assessment of balance of risks between teratogenicity and
      seizure control.

PMID- 16796591
TI  - Neuromyelitis optica associated with myasthenia gravis: characteristic phenotype
      in Japanese population.
AB  - We report two female patients with neuromyelitis optica (NMO, Devic's syndrome)
      following or coincidental with myasthenia gravis (MG). Their illnesses were
      characterized by subacute myelitis with optic neuritis, high serum levels of
      muscle acetylcholine receptor antibody, and autoimmune thyroid disease. Both
      patients fulfilled the clinical criteria of NMO, however, NMO-IgG, autoantibody
      against aquaporin-4 water channel, was absent from their sera. Both NMO and MG
      are relatively rare diseases. The considerable coincidence of these two disorders
      suggests that there is a subgroup of patients with NMO having a common
      immunological pathogenesis with MG.

PMID- 16796592
TI  - A case of cerebral Whipple's disease initially presenting with isolated focal
      myoclonus.
AB  - Neurological manifestations in Whipple's disease are highly variable and tend to
      occur at later stages of the disease. However, isolated, focal neurological
      symptoms are reported to be rare. Here we describe the successful treatment of a
      case of cerebral Whipple's disease initially presenting solely with isolated
      myoclonic jerks of the left hand and forearm evolving to a segmental myoclonus at
      a later stage. Additionally, we present - to our knowledge - a novel treatment by
      administration of immunomodulatory therapy (IVIg) in addition to established
      antibiotics.

PMID- 16796593
TI  - Guillain-Barre syndrome in Pakistan: similarity of demyelinating and axonal
      variants.
AB  - Guillain-Barre syndrome (GBS) comprises multiple subtypes whose nosological and
      pathophysiologic interrelationships are unclear. In an attempt to better
      understand the relationship between the disease's major subtypes, we reviewed the
      characteristics of GBS cases consecutively admitted to a tertiary care hospital
      in Karachi, Pakistan, over a 13-year period. Of 175 cases, 80 (46%) were
      demyelinating and 55 (31%) axonal, whilst 40 (23%) had ambiguous
      electrophysiological findings precluding classification. The three groups
      differed in severity of weakness at presentation (axonal approximately ambiguous
      > demyelinating; P = 0.002 for arm strength and P = 0.025 for leg strength); mean
      age (demyelinating > axonal > ambiguous; P = 0.05); and mean cerebrospinal fluid
      protein concentration (demyelinating > ambiguous > axonal; P = 0.05). However,
      they were similar in several other respects, including gender ratio, proportion
      of pediatric cases, history of antecedent infection, length of hospital stay,
      need and duration of mechanical ventilation, and functional outcome at discharge.
      Stool culture data was available for 146 (83%) cases in the study; none was
      positive for Campylobacter jejuni. GBS in Pakistan comprises a high proportion of
      axonal cases. Similarity of outcomes in axonal and demyelinating variants and
      lack of C. jejuni stool culture positivity are atypical features.

PMID- 16796594
TI  - Triptan responsive hypnic headache?

PMID- 16796595
TI  - Message for caregivers of dementia with Lewy bodies patients: hallucinations can
      be pleasurable for your patient. Cope with your embarrassment and empathize.

PMID- 16796596
TI  - Hemidystonia as initial manifestation of sporadic Creutzfeldt-Jakob disease.

PMID- 16796597
TI  - Treatment of an acute attack of porphyria during pregnancy.

PMID- 16796598
TI  - Treatment response and electrophysiological criteria in chronic inflammatory
      demyelinating polyneuropathy.

PMID- 16796599
TI  - Isolated unilateral abducens palsy in idiopathic intracranial hypertension
      without papilledema.

PMID- 16796600
TI  - Generalized status epilepticus possibly induced by gatifloxacin.

PMID- 16796601
TI  - Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated
      dementia.
AB  - Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages
      and microglia secrete neurotoxins. Two of these neurotoxins are the pro
      inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta), which are thought to play a major role in inducing neuronal
      death. Both TNF-alpha and IL-1beta increase the permeability of the blood-brain
      barrier, through which subsequently HIV-infected monocytes can enter the brain.
      They both induce over-stimulation of the NMDA-receptor via several pathways,
      resulting in a lethal neuronal increase in Ca(2+) levels. Additionally, TNF-alpha
      co-operates with several other proinflammatory mediators to enhance their toxic
      effects. Although most research has focused on the neurotoxic effects of TNF
      alpha and IL-1beta in HAD, there is also evidence that these cytokines can be
      neuroprotective. In this paper the effect of TNF-alpha and IL-1beta on neuronal
      life and death in HAD is discussed.

PMID- 16796602
TI  - Smoking is associated with insulin resistance and cardiovascular autonomic
      dysfunction in type 2 diabetic patients.
AB  - BACKGROUND: Smoking and cardiovascular autonomic dysfunction are associated with
      high mortality in type 2 diabetic patients. This study tested the hypothesis that
      smoking is associated with insulin resistance/hyperinsulinaemia and
      cardiovascular autonomic dysfunction in type 2 diabetic patients who are not
      treated with insulin. MATERIALS AND METHODS: The study patients were 22 current
      smokers with type 2 diabetes mellitus (age: 57 +/- 5 years, mean +/- SD) and 30
      age-matched never-smoked patients with type 2 diabetes mellitus (control group,
      57 +/- 8 years). The quality of blood glucose was assessed by fasting plasma
      glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model
      assessment (HOMA) index and haemoglobin A1c (HbA1c). The severity of smoking
      status was expressed by the Brinkman index, which is calculated as number of
      cigarettes per day multiplied by years of smoking. Cardiovascular autonomic
      function was assessed by baroreflex sensitivity (BRS), heart-rate variability,
      plasma norepinephrine concentration and cardiac (123)I-metaiodobenzylguanidine
      (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the
      current smokers group than in the never-smoked group (P < 0.05). Early and
      delayed (123)I-MIBG myocardial uptake values were lower (P < 0.05, and P < 0.01,
      respectively) and the percentage washout-rate of (123)I-MIBG was higher (P <
      0.0001) in the current smokers group than in the never-smoked group. Fasting
      immunoreactive insulin (F-IRI) concentration (P < 0.0001) and the homeostasis
      model assessment (HOMA) index (P < 0.0001) were higher in the current smokers
      group than the never-smoked group. Multiple logistic regression analysis revealed
      that smoking was independently predicted by F-IRI and the percentage washout-rate
      of (123)I-MIBG. CONCLUSIONS: The results of the study suggested that smoking was
      associated with cardiovascular autonomic dysfunction and hyperinsulinaemia and
      that F-IRI and the percentage washout-rate of (123)I-MIBG were independent
      predictors of smoking in these Japanese patients with type 2 diabetes mellitus.

PMID- 16796603
TI  - Cardiac troponin I and ventricular arrhythmia in patients with chronic heart
      failure.
AB  - BACKGROUND: Both detectable serum cardiac troponin I (cTnI) and ventricular
      dysrhythmias are common in patients with chronic heart failure (CHF) and are
      paralleled with the severity of the CHF. However, the relationship between serum
      cTnI and ventricular arrhythmia severity in patients with CHF remains unknown;
      the mechanism of the ventricular arrhythmia in the CHF patients also remains
      unclear. MATERIALS AND METHODS: The study group included 218 patients with CHF
      who had cTnI assay drawn at the time of initial presentation. Patients with acute
      myocardial infarction or myocarditis were excluded from the analysis. The
      patients were divided into two groups: cTnI-positive with serum cTnI > 0.5 ng mL(
      1) (n = 98) and cTnI-negative with serum cTnI < or = 0.5 ng mL(-1) (n = 120). The
      severity of ventricular dysrhythmias was assessed by 24-h Holter monitoring,
      using prospectively defined measures of ventricular arrhythmic burden. RESULTS:
      Prevalence of risk factors for ventricular dysrhythmias was equal in both groups.
      All measures of ventricular ectopy were much higher in patients of the cTnI
      positive groups. Mean hourly ventricular pairs (13.59 +/- 10.3 vs. 11.1 +/- 6.01,
      P = 0.027), mean hourly repetitive ventricular beats (26.01 +/- 13.67 vs. 22.01
      +/- 13.56, P = 0.032), and the frequency of ventricular tachycardia episodes per
      24 h (12.54 +/- 16.68 vs. 7.68 +/- 11.54, P = 0.012) were higher in patients with
      detectable cTnI levels. After inclusion of clinical variables and drug therapies
      in a multivariate analysis, the positive relationship between cTnI and the
      frequency of ventricular pairs (P = 0.03), repetitive ventricular beats (P =
      0.037), and ventricular tachycardia (P = 0.03) remained independent. In
      multivariate logistic regression, the risk of developing ventricular tachycardia
      was higher in patients with detectable cTnI levels with an adjusted odds ratio
      (OR) of 2.31 (95% CI, 1.22-2.65, P = 0.003). CONCLUSIONS: In patients with CHF,
      serum cTnI is closely related to increased occurrence of ventricular dysrhythmias
      and could identify a subgroup of patients with ventricular tachycardia. The
      minimal myocardial injury detected by serum cTnI might be the abnormal substrate
      for ventricular dysrhythmias.

PMID- 16796604
TI  - TGF-beta1 generates a specific multicomponent extracellular matrix in human
      coronary SMC.
AB  - BACKGROUND: Transforming growth factor (TGF-beta(1)) is postulated to play an
      important role in maintaining the structure and function of arterial tissue and
      protection against development of arteriosclerosis. The TGF-beta(1)-induced
      production of a stable extra-cellular matrix-rich plaque phenotype is suggested
      to be part of the protection against a switch to an unstable rupture-prone
      arteriosclerotic plaque. MATERIALS AND METHODS: This study addresses the question
      of whether the expression profile and the type of extra-cellular matrix (ECM)
      generated by TGF-beta(1) stimulation have the structural feature of a fibril-rich
      stable matrix. Seventeen genes codings for ECM components of human coronary
      smooth muscle cells (SMCs) after a 24-h stimulation by TGF-beta(1) have been
      analyzed. RESULTS: Real-time RT-PCR was used to quantify the mRNA of genes under
      investigation. It was found that after TGF-beta(1) stimulation (a) the up
      regulation of COL1A1-specific mRNA was associated with increased [(3)H]proline
      incorporation into the alpha-1 and -2 chains of collagen type I, (b) the up
      regulation of biglycan- and syndecan-1-specific mRNA corresponded to an increased
      [(35)S]sulphate and [4,5-(3)H]leucine incorporation into the biglycan molecule
      and to an increase of syndecan-1 protein, (c) the up-regulated FGF-2 gene
      accounted predominantly for the ECM-bound subfraction of FGF-2-protein and (d)
      fibronectin and thrombospondin exhibited a significantly higher mRNA level. In
      contrast collagen XIV, a minor collagen type, and the proteoglycan decorin were
      down-regulated. The down-regulated decorin changed its structure by elongation
      and reduced GlcA to IdoA epimerization of the dermatan sulphate side-chain as
      judged by [(35)S]sulphate metabolic labelling experiments. No significant changes
      in response to TGF-beta(1) were observed for the collagen types III, VI and XVI,
      for versican, perlecan and the syndecans-2 and -4. CONCLUSIONS: It was concluded
      from the data that the TGF-beta(1)-induced formation of a highly specific
      multicomponent extra-cellular matrix on coronary arterial SMCs could provide in
      vivo mechanical strength to the neointima in arteriosclerotic lesions and to the
      fibrous cap overlying the lipid core.

PMID- 16796605
TI  - Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids.
AB  - BACKGROUND: Anabolic androgenic steroids are used by some bodybuilders to enhance
      performance. While the cardiovascular implications of supraphysiological androgen
      levels requires further clarification, use is associated with sudden death, left
      ventricular hypertrophy, thrombo-embolism and cerebro-vascular events. MATERIALS
      AND METHODS: To further understand the effect of androgenic anabolic steroid
      abuse on vascular function, this study assessed vascular stiffness (pulse-wave
      analysis) and cardiovascular risk factors in 28 male, bodybuilding subjects, of
      whom ten were actively receiving anabolic agents (group A; 26.4 +/- 7.2 years)
      and eight had undergone a 3-month "wash-out" period (group B; 32.1 +/- 7.1
      years). The remaining ten bodybuilding subjects (group C; 24.4 +/- 4.4 years)
      denied any past use of anabolic steroids or other performance enhancing drugs.
      Comparisons were made with ten sedentary male controls (group D, 29.3 +/- 4.7
      years). RESULTS: Endothelial independent dilatation in response to glycerol
      trinitrate was significantly impaired in the group currently using anabolic
      steroids (group A) compared with the other three groups [A (5.63 +/- 3.24%)
      versus; B (11.10 +/- 4.91%), C (17.88 +/- 9.2%) and D (14.46 +/- 3.9%), P <
      0.0005, respectively], whereas no significant differences in endothelial
      dependent dilatation were detected between the groups [A (5.0 +/- 3.0%), B (7.4
      +/- 3.4%), C (9.6 +/- 4.5%) and D (8.2 +/- 3.3%), P < 0.059, respectively].
      CONCLUSIONS: Previous studies described a decline in vascular reactivity
      occurring in bodybuilding subjects which is independent of anabolic steroid use
      and may result from smooth muscle hypertrophy with increased vascular stiffness.
      This study revealed impaired vascular reactivity associated with anabolic agents
      and that improvement in vascular function may occur following their
      discontinuation.

PMID- 16796606
TI  - Effect of an acute hyperinsulinaemic clamp on post-prandial lipaemia in subjects
      with insulin resistance.
AB  - BACKGROUND: Obese, insulin-resistant individuals have raised levels of intestinal
      and hepatic lipoproteins. Insulin decreases the production of hepatic
      lipoproteins in vivo and so this study aimed to investigate whether an acute
      hyperinsulinaemic, euglycaemic clamp could correct fasting and post-prandial
      dyslipidaemia. SUBJECTS AND METHODS: In a randomized, cross-over design, post
      prandial lipaemia was compared in subjects infused either with insulin to achieve
      a steady-state concentration of 100 mU L(-1) or with saline. Nine obese (Body
      Mass Index > 26 kg m(-2); waist : hip > 1.0) insulin-resistant (Homeostatic Model
      Assessment score > 2.0) male subjects were given an oral fat load 3 h after the
      infusions began, and sampling continued for 6 h. Plasma apoB-48, triglyceride and
      nonesterified fatty acid (NEFA) were measured hourly. RESULTS: Average steady
      state serum insulin levels during the hyperinsulinaemic clamp were 123 +/- 4.4 mU
      L(-1). A paired analysis showed no net effect of insulin on post-prandial
      chylomicron metabolism when calculated as the (apoB-48) incremental area under
      the curve (IAUC). However, there was a trend towards a delay in the apoB-48 peak,
      consistent with possible changes in the rates of chylomicron biogenesis,
      lipolysis and/or clearance. Similarly, post-prandial lipaemia (depicted as
      triglyceride IAUC) was similar for subjects infused with insulin or saline, but
      the peak post-prandial response was delayed during insulin infusion. The NEFA
      were rapidly decreased by 83% after 3 h of insulin infusion. CONCLUSIONS: In
      obesity and insulin resistance, short-term changes in plasma insulin do not
      appreciably exert a regulatory effect on exogenously-derived post-prandial
      lipoproteins. The data suggest that hyperchylomicronaemia in insulin-resistant
      subjects is a result of chronic aberrations in insulin-mediated regulation of
      post-prandial lipid metabolism.

PMID- 16796607
TI  - Infection induced inflammation is associated with erectile dysfunction in men
      with diabetes.
AB  - BACKGROUND: In diabetic patients with erectile dysfunction, endothelial
      dysfunction is a major underlying cause. Infection-induced inflammation may be
      associated with endothelial dysfunction. The goal of this study was to determine
      whether erectile dysfunction in patients with diabetes is associated with
      infections of Chlamydia pneumoniae or cytomegalovirus and/or with low-grade
      inflammation. MATERIALS AND METHODS: Diabetic patients, 57 with and 33 without
      erectile dysfunction, were enrolled in a case-control study. Both groups of
      patients consists of type 1 and type 2 diabetics. Serum antibodies against
      cytomegalovirus and C. pneumoniae and markers of inflammation, including high
      sensitivity C-reactive protein and fibrinogen, were measured. RESULTS: Adjusted
      odds ratios for erectile dysfunction in cytomegalovirus IgG, C. pneumoniae IgG
      and C. pneumoniae IgA seropositive men were 2.4 (95%CI; 1.0-6.0), 3.0 (95%CI; 1.2
      8.1) and 1.8 (95%CI; 0.7-4.6), respectively. Odds ratios for the highest tertiles
      of high-sensitivity C-reactive protein and fibrinogen concentrations compared to
      the lowest tertile were 4.3 (95%CI; 1.4-13.1) and 6.6 (95%CI; 2.1-21.2),
      respectively. CONCLUSION: Elevated high-sensitivity C-reactive protein or
      fibrinogen serum levels and infection with cytomegalovirus or C. pneumoniae were
      associated with erectile dysfunction in diabetes. The relation between
      cytomegalovirus and erectile dysfunction is markedly present in patients with
      elevated high-sensitivity C-reactive protein and fibrinogen levels, suggesting a
      modifying effect by the inflammation.

PMID- 16796608
TI  - Circulating ghrelin levels after food intake during different phases of the
      migrating motor complex in man.
AB  - BACKGROUND: The timing of the migrating motor complexes (MMC) at food intake may
      influence gastric emptying and release of regulatory hormones. This report
      studies the relationships between phases I (motor quiescence) and II
      (intermediate frequency contractions) of MMC and prandial gut hormone response.
      MATERIALS AND METHODS: Seven fasting volunteers ingested a meal during phase I or
      II of MMC verified by manometry, using paracetamol as a marker for gastric
      emptying. Blood was sampled before, during and 210 min after food intake for
      analysis of ghrelin, motilin, insulin and paracetamol. RESULTS: The basal level
      of ghrelin during phase I was 127.5 +/- 25.4 pmol L(-1) and during phase II was
      132.4 +/- 24.8 pmol L(-1). After food intake during phase I, ghrelin fell to 77.2
      +/- 10 pmol L(-1); in phase II it fell to 82.7 +/- 17.8 pmol L(-1) within 60 min
      and returned to baseline levels after 120 min. Baseline levels of motilin were 16
      +/- 2 pmol L(-1) and 18 +/- 3 pmol L(-1) during phases I and II, respectively.
      After food, motilin decreased to 8.5 +/- 0.7 pmol L(-1) and 8.7 +/- 1.0 pmol L(
      1) within 60 min and returned to baseline after 90 min. Insulin levels in phases
      I and II were 8.1 +/- 1.2 mU L(-1) and 8.6 +/- 0.7 mU L(-1), respectively,
      reaching 138.9 +/- 35.6 mU L(-1) and 167.4 +/- 30.0 mU L(-1) at 45 min
      postprandially. CONCLUSIONS: The nutritional status of the gastrointestinal tract
      at food intake had only a limited impact on plasma ghrelin. After food intake,
      plasma ghrelin drops, similar to motilin, and resumes preprandial levels within
      120 min.

PMID- 16796609
TI  - Sounding airflow enhances aerosol delivery into the paranasal sinuses.
AB  - BACKGROUND: The use of aerosol therapy is commonly suggested in the treatment of
      paranasal disorders but it is difficult to achieve an effective penetration of
      drugs into the sinuses. The authors have recently shown that an oscillating
      airflow produced by phonation (nasal humming) causes a large increase in the gas
      exchange between the nose and the paranasal sinuses. This is reflected by a high
      peak in nasally exhaled nitric oxide (NO) levels because NO accumulated in the
      sinuses is rapidly washed-out via the sinus ostia. OBJECTIVE: This study was
      designed to test whether the increase in sinus gas exchange caused by an
      oscillating airflow could be used to enhance penetration of a drug into the
      sinuses. MATERIALS AND METHODS: In six healthy subjects a nitric oxide-synthase
      inhibitor L-NAME was administrated into the nostrils by a jet nebulizer connected
      to a duck call, which could be modified to generate either a sounding airflow or
      a non-sounding airflow. The degree of L-NAME penetration into the sinuses was
      judged from the reduction in nasal NO during humming exhalations. Sinus drug
      deposition was also studied in a model of the nose and sinus. RESULTS: In humans
      the delivery of L-NAME with the non-sounding airflow had no effect on the NO
      levels achieved during humming, whereas L-NAME administration with sound caused a
      significant 22-35% reduction in nasal NO. In the model the aerosol delivery with
      the sounding airflow caused a fourfold increase in sinus drug deposition as
      compared with an aerosol without sound. CONCLUSION: A sounding airflow increases
      the delivery of an aerosolized drug into the paranasal sinuses.

PMID- 16796610
TI  - Higher renal extraction of ANP compared with NT-proANP, BNP and NT-proBNP.

PMID- 16796613
TI  - Relative abundance and survival of the tick Amblyomma americanum collected from
      sunlit and shaded habitats.
AB  - The population density of host-searching nymphal and adult lone star ticks,
      Amblyomma americanum (L.) (Acari: Ixodidae), was determined at the Robinson tract
      of the Kansas Ecological Reserves and a private farm 5 km north-west of the
      Robinson tract using standard drag cloth methods. Nymphs, males and females were
      counted and collected weekly from shaded habitats and adjacent sunlit habitats
      from mid-May through late July, 2003. Of the 1598 nymphs and 549 males collected
      by drag sampling, 74.0% and 72.1%, respectively, were collected from shaded
      sections of the habitats, whereas 77.3% of 472 females were found in sunlit
      sections. A. americanum collected during each sampling period were maintained
      unfed at >95% relative humidity and a 14 : 10 h photoperiod, and survival was
      recorded weekly until all ticks had died. Survival of nymphs, males and females
      did not differ between ticks collected in the shade vs. those collected in the
      sun. Nymphs survived significantly longer than adults, whereas male and female
      survival did not differ from each other. These results suggest that host
      searching A. americanum populations may partition their environment to increase
      the chances of coming into contact with a potential vertebrate host.

PMID- 16796612
TI  - Effect of forest clearing on the abundance of Ixodes ricinus ticks and the
      prevalence of Borrelia burgdorferi s.l.
AB  - Questing Ixodes ricinus L. (Acari: Ixodidae) ticks were collected on a forest
      trail that had been completely cleared of shrubs and ground vegetation in winter
      2002 and on a nearby control uncleared forest transect in South Moravia (Czech
      Republic). Samples were collected each May in 2003, 2004 and 2005. Nymphal ticks
      were 3.4 times, 1.9 times and 1.2 times less frequent on cleared forest than on
      uncleared forest trails in the three respective years, whereas adult tick
      abundance was 27.2 times, 4.0 times and 2.2 times lower, respectively. The ticks
      were examined for borreliae by dark-field microscopy: prevalence of nymphal ticks
      infected with Borrelia burgdorferi sensu lato (12.6% to 20.0%) did not differ
      significantly between the cleared and uncleared trail during the 3 years. In
      conclusion, the habitat modification appeared to result in a decreased abundance
      of I. ricinus as well as a reduced frequency of infected ticks (and thus
      indirectly a lower potential risk of Lyme borreliosis), which lasted, however,
      for only 2 years. Eight cultures of borreliae isolated from the ticks were all
      identified as the 'ornithophilic' genomic species Borrelia garinii, possibly
      indicating a greater role of forest birds than that of forest rodents as the
      hosts of immature I. ricinus in the tick (and borrelial) colonization of the
      cleared part of the forest.

PMID- 16796614
TI  - Risk factors associated with ixodid tick species distributions in the Basque
      region in Spain.
AB  - Ixodid tick abundance was investigated in the Basque region in Spain in two 1
      year longitudinal studies, in 1992-1993 and 2003-2004. Forty zones were visited
      monthly and 162 672 ticks (87% larvae, 12% nymphs and 1% adults) were collected
      by blanket dragging. Eleven tick species belonging to the genera Ixodes,
      Haemaphysalis, Rhipicephalus and Dermacentor were identified including
      Haemaphysalis concinna Koch, which had not previously been reported in Spain.
      Tick species abundance differed between zones, studies and seasons. In 1992-1993,
      Haemaphysalis punctata Canestrini & Fanzago was the predominant species and
      distinct spring-summer and autumn-early winter peaks of activity were observed.
      In 2003-2004, Ixodes ricinus (Linneaus) was the most common species and was
      active throughout the winter. Larval and nymph seasonal activity patterns
      coincided in both 1993 and 2003 and this could facilitate co-feeding transmission
      of pathogens. Higher tick abundance was associated with increased livestock
      abundance in 1992-1993 and milder winter temperatures in 2003-2004. Tick
      collection rates in areas with moderate and high tick density were positively
      associated with the interaction between ambient temperature at sampling and
      rainfall 7 days prior to sampling. Collection rates were also significantly
      higher at medium rather than higher altitude, in forested areas than in open
      grasslands and lower in recreational areas frequented by people and with wet
      vegetation at sampling.

PMID- 16796615
TI  - Phylogenetic analysis of Culicoides species from France based on nuclear ITS1
      rDNA sequences.
AB  - Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) play important
      roles in the transmission of viral diseases affecting wild and domestic ruminants
      and horses, including Bluetongue (BT) and African horse sickness (AHS)
      respectively. In southern Europe, BT has been largely transmitted by the
      classical Afro-Asian vector Culicoides imicola Kieffer. However, other species
      such as C. obsoletus Meigen, C. scoticus Downs & Kettle and C. pulicaris Linne
      may also be involved in BTV transmission. As a consequence of the discovery of C.
      imicola followed by BTV-2 outbreaks on the island of Corsica in October 2000,
      further studies on these biting midges have been carried out. To better
      characterize the evolution and phylogenetic relations of Culicoides, molecular
      analysis in parallel with a morphology-based taxonomic approach were performed.
      Phylogenetic analyses of French Culicoides species were undertaken using the
      ribosomal DNA (rDNA) internal transcribed spacer 1 (ITS1) as a molecular target.
      This region was shown to be useful in understanding evolutionary and genetic
      relationships between species. Construction of several trees showed that
      molecular phylogeny within the genus Culicoides correlates not only with
      morphological-based taxonomy but also with ecological patterns.

PMID- 16796616
TI  - Phylogeny of the subgenus Culicoides and related species in Italy, inferred from
      internal transcribed spacer 2 ribosomal DNA sequences.
AB  - Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) include vectors
      for the economically important animal diseases, bluetongue (BT) and African horse
      sickness (AHS). In the Mediterranean Basin, these diseases are transmitted by
      four species of Culicoides: the first three belong in the subgenus Avaritia Fox
      and are Culicoides imicola Kieffer, Culicoides obsoletus (Meigen) and Culicoides
      scoticus Downes and Kettle; the fourth is Culicoides pulicaris (Linnaeus) in the
      subgenus Culicoides Latreille. In the Palaearctic Region, this subgenus (usually
      referred to as the C. pulicaris group) now includes a loose miscellany of some 50
      taxa. The lack of clarity surrounding its taxonomy stimulated the present
      morphological and molecular study of 11 species collected in Italy. Phylogenetic
      analysis of nuclear ribosomal DNA internal transcribed spacer 2 (ITS2) sequence
      variation demonstrated a high degree of divergence. These results, combined with
      those from a parallel morphological study, disclosed: (1) that some previously
      described taxa should be resurrected from synonymy; (2) that there are new
      species to be described; (3) that the subgenus Culicoides (as currently employed)
      is a polyphyletic assemblage of four lineages - the subgenus Culicoides sensu
      stricto, the subgenus Silvicola Mirzaeva and Isaev, the subgenus Hoffmania Fox
      and the hitherto unrecognized Fagineus species complex. Each is discussed briefly
      (but not defined) and its constituent Palaearctic taxa listed. Strong congruence
      between morphological and molecular data holds promise for resolving many of the
      difficult taxonomic issues plaguing the accurate identification of vector
      Culicoides around the world.

PMID- 16796617
TI  - Effect of investigator disturbance in experimental forensic entomology:
      succession and community composition.
AB  - Carrion insect succession studies have historically used repeated sampling of
      single or a few carcasses to produce data, either weighing the carcasses,
      removing a qualitative subsample of the fauna present, or both, on every visit
      over the course of decomposition and succession. This study, conducted in a set
      of related experimental hypotheses with two trials in a single season,
      investigated the effect that repeated sampling has on insect succession,
      determined by the number of taxa collected on each visit and by community
      composition. Each trial lasted at least 21 days, with daily visits on the first
      14 days. Rat carcasses used in this study were all placed in the field on the
      same day, but then either sampled qualitatively on every visit (similar to most
      succession studies) or ignored until a given day of succession, when they were
      sampled qualitatively (a subsample) and then destructively sampled in their
      entirety. Carcasses sampled on every visit were in two groups: those from which
      only a sample of the fauna was taken and those from which a sample of fauna was
      taken and the carcass was weighed for biomass determination. Of the carcasses
      visited only once, the number of taxa in subsamples was compared to the actual
      number of taxa present when the carcass was destructively sampled to determine if
      the subsamples adequately represented the total carcass fauna. Data from the
      qualitative subsamples of those carcasses visited only once were also compared to
      data collected from carcasses that were sampled on every visit to investigate the
      effect of the repeated sampling. A total of 39 taxa were collected from carcasses
      during the study and the component taxa are discussed individually in relation to
      their role in succession. Number of taxa differed on only one visit between the
      qualitative subsamples and the actual number of taxa present, primarily because
      the organisms missed by the qualitative sampling were cryptic (hidden deep within
      body cavities) or rare (only represented by very few specimens). There were no
      differences discovered between number of taxa in qualitative subsamples from
      carcasses sampled repeatedly (with or without biomass determinations) and those
      sampled only a single time. Community composition differed considerably in later
      stages of decomposition, with disparate communities due primarily to small
      numbers of rare taxa. These results indicate that the methods used historically
      for community composition determination in experimental forensic entomology are
      generally adequate.

PMID- 16796618
TI  - Nephrogenic fibrosing dermopathy: lessons from the past.

PMID- 16796619
TI  - Polymorphic eruption of pregnancy.
AB  - Polymorphic eruption of pregnancy (PEP) is a benign, self-limiting, pruritic
      disorder of pregnancy, which usually affects the primigravida during the last
      trimester or immediately postpartum. Its pathogenesis is unclear and its clinical
      manifestations are variable, leading frequently to an incorrect diagnosis. In
      cases of PEP the histological findings are nonspecific and the laboratory
      results, including direct immunofluorescence (DIF) and indirect
      immunofluorescence (IIF), are negative. Polymorphic eruption of pregnancy is not
      associated with any fetal risk and symptomatic treatment is all that is usually
      required. In this review we present the clinical presentation of PEP and a
      differential diagnosis which defines PEP as a separate entity. We will also
      review all current data of possible etiologic factors, histologic and immunologic
      findings, prognosis and therapy.

PMID- 16796621
TI  - Diagnostic accuracy in skin cancer clinics: the Australian experience.
AB  - BACKGROUND: Australia, with the world's highest incidence of skin cancer, has
      witnessed the emergence of "open access" skin cancer clinics during the past
      decade. These clinics are becoming increasingly popular destinations for the
      diagnosis and treatment of skin cancers, yet little is known about the diagnostic
      performance of practitioners in this setting. We sought to measure the accuracy
      of clinical diagnosis in this setting. METHODS: Clinical and histological data
      were obtained from 199 consecutive patients undergoing biopsy or excision for 287
      skin lesions. We measured the sensitivity, specificity and predictive value of
      the clinical diagnoses compared with histological diagnoses. RESULTS: Of 287
      biopsied or excised lesions, the most common were benign nevi (24%) and basal
      cell carcinomas (22%), followed by actinic keratoses (11%), dysplastic nevi (11%)
      and squamous cell carcinomas (7%). Sensitivity was highest for diagnosing BCC
      (0.89, 95%CI 0.78-0.95) and dysplastic nevi (0.80, 95%CI 0.61-0.93), and lowest
      for actinic keratoses and the group of benign lesions. Specificity was greater
      than 0.93 for all diagnoses except BCC (0.76, 95%CI 0.70-0.81). Treating
      clinicians perceived moderate to strong pressure to excise 49% of lesions
      overall, but in particular for benign nevi (73%). CONCLUSIONS: Australian family
      practitioners in open access skin cancer clinics diagnose a wide range of skin
      lesions with high specificity and moderate to high sensitivity. Benign nevi are
      accurately diagnosed and often excised because of patient pressure.

PMID- 16796620
TI  - Repigmentation of vitiligo with punch grafting and narrow-band UV-B (311 nm)--a
      prospective study.
AB  - BACKGROUND: Phototherapy is already established as an effective mode of therapy
      in vitiligo. An evidence-based study was carried out of the effect of narrow-band
      (311 nm) ultraviolet-B (NB-UV-B) radiation in 66 surgically treated patients with
      recalcitrant vitiligo in whom autologous mini-punch grafting was deployed.
      METHODS: A total of 2613 grafts were placed over 108 lesions on 17 regions in 66
      individuals (39 females and 27 males) with stable, refractory vitiligo. The age
      range was 21-48 years. Postsurgically, they were exposed to a suberythemal dose
      of NB-UV-B (311 nm). Different parameters of surgical repigmentation were
      documented. RESULTS: Successful repigmentation was achieved in 57 (86.36%) cases.
      The appearance of repigmentation (AOR) time in different regions varied between
      14 and 32 days, with an overall average of approximately 20.6 days. Maximum
      pigment spread (MPS) reached 12 mm with an average of 6.5 mm. The relationship
      between the donor graft area and area of surgical repigmentation was also
      calculated. Cobblestoning was the most common (31.8%) complication, but improved
      with time and/or interference. CONCLUSIONS: Punch grafting in combination with
      phototherapy (NB-UV-B, 311 nm) was found to be an easy, safe, inexpensive, and
      effective method of repigmenting static and stubborn vitiligo. Different facets
      of punch grafting-induced and phototherapy-aided surgical repigmentation were
      taken into consideration. The area of repigmentation, MPS, and relationship
      between the donor graft area and area of surgical repigmentation were documented.

PMID- 16796622
TI  - Quinine sulfate inhibits invasion of some bacterial skin pathogens.
AB  - BACKGROUND: As some of the many patients who receive antimalarials for the
      treatment of noninfective inflammatory diseases (lupus erythematosus, collagen
      vascular diseases, rheumatoid arthritis, and others) are also immunosuppressed
      because of their disease and/or treatments, and may have concomitant bacterial
      infections, we investigated the effect of these drugs on the growth and invasion
      of several bacteria that are commonly associated with skin and soft tissue
      infections to determine whether they could protect against such conditions and
      obviate the need for an additional antibiotic drug. METHODS: The effect of
      quinine sulfate (QS) at concentrations of 50 and 100 microm on the entry process
      of Enterobacter agglomerans, Staphylococcus aureus, Pseudomonas aeruginosa, and
      Klebsiella pneumoniae into Caco-2 cells was studied during the infection period.
      The invasive efficiency was expressed as the number of viable internalized
      bacteria obtained by counting the colony-forming units (CFUs). RESULTS: The
      invasive ability of E. agglomerans and S. aureus was significantly inhibited by
      50 and 100 microm QS in a dose-dependent manner when the drug was added to Caco-2
      cell monolayers during the infection period; however, QS had no significant
      effect on the internalization of P. aeruginosa or K. pneumoniae. DISCUSSION AND
      CONCLUSIONS: Antimalarial drugs are currently widely used to treat patients with
      autoimmune dermatologic and rheumatologic diseases, and have also been recently
      proposed as additional therapy for patients with human immunodeficiency virus
      (HIV) infection. These patients, who are often immunocompromised, may receive a
      secondary advantage from these antimalarials, which may provide some protection
      against staphylococci (amongst the most important human pathogens causing many
      superficial and systemic infections) and E. agglomerans.

PMID- 16796623
TI  - Hemodialysis-related pruritus and associated cutaneous manifestations.
AB  - BACKGROUND: Uremic pruritus is one of the most common disabling problems in
      patients with chronic renal failure. Few studies have evaluated itching and
      cutaneous manifestations in hemodialysis-dependent patients. OBJECTIVES: The aim
      of this prospective study was to identify the prevalence of pruritus and
      cutaneous changes affecting patients undergoing hemodialysis. METHODS: The degree
      of itching in 70 patients treated at the Haemek Medical Center Hemodialysis Unit,
      in northern Israel, was scored according to presence and severity. We examined
      the relationship between the quality of dialysis and the frequency of pruritus,
      and identified concurrent cutaneous disorders. RESULTS: Pruritus was a common
      problem in the study cohort and affected 74.3% of hemodialysis patients at some
      point. The main characteristics of pruritus were a general pattern in 65.7% and
      mild intensity in 78.3% of observed patients. Duration of hemodialysis varied
      between 3 months and 13 years. There was no correlation between occurrence of
      pruritus and demographic or medical parameters (sex, type of kidney disease,
      regular medications or duration of hemodialysis) of the patients. Higher dialysis
      efficacy, as expressed by dialyser clearance, volume distribution of area,
      dialysis duration (Kt/v), may reduce the prevalence of pruritus (P < 0.02). None
      of the blood and chemical values considered (hemoglobin, creatinine, urea,
      phosphorus, calcium, albumin, parathormone and alkaline phosphatase) revealed any
      statistically relevant differences between pruritus groups. The appearance of
      foot ulcers was different between diabetic and nondiabetic individuals undergoing
      hemodialysis (P < 0.001). CONCLUSIONS: Pruritus is still a common problem in
      hemodialysis-dependent patients. The prevalence of xerosis and excoriations was
      high in patients undergoing replacement therapy. Efficient replacement
      hemodialysis may provide a clinical benefit.

PMID- 16796624
TI  - Determination of survival and hazard functions for pemphigus patients in Kerman,
      a southern province of Iran.
AB  - BACKGROUND: Pemphigus has in the past been associated with a high mortality rate.
      However, with the discovery of corticosteroids, patient median survival has
      improved. Our purpose was to assess median survival after confirmed diagnosis of
      pemphigus in patients in Kerman, a southern province of Iran. METHODS: All
      patients who were either admitted to the hospital or treated as outpatients in
      Kerman from 22 September 1987 to 22 September 1999 and who had confirmed
      pemphigus were included in the study. Survival was estimated using the Kaplan
      Meier method, and the following variables were evaluated in a univariate analysis
      for an association with survival: age, sex, type of pemphigus, and type of
      therapy. RESULTS: A total of 55 patients (38 female and 17 male) were identified.
      No significant differences were found between genders. The mean age at the time
      of diagnosis was 46.0 years. Older groups had a lower survival rate than younger
      groups (P < 0.001). The majority (82%) of cases were vulgaris/vegetans, and no
      significant differences were found in 10-year survival for type of pemphigus (P >
      0.05). The patients who had been treated with corticosteroids alone had longer
      median survival times than those who had been treated with corticosteroids plus
      azathioprine (P < 0.001). A total of 11 patients died; the median follow-up time
      for those still alive was 5.9 years (range 2-12 years). Estimated survival at 2,
      6 and 10 years was 92.7, 86.8 and 61.5%, respectively. CONCLUSION: Overall median
      survival rate in patients with pemphigus was 10 years, regardless of gender or
      subtype of pemphigus. Survival was adversely affected by late onset. Those
      patients treated with immunosuppressives and corticosteroids also appeared to
      have reduced survival times when compared to those treated with corticosteroids
      alone.

PMID- 16796625
TI  - The prevalence of skin diseases in the elderly: analysis of 4099 geriatric
      patients.
AB  - BACKGROUND: The geriatric population is composed of persons over 65 years of age,
      and few studies are available on the dermatologic diseases in this group.
      METHODS: Data on a total of 4099 geriatric patients admitted between the years
      1999-2003 were analyzed. Hospital-based patient registry records were used for
      data collection. The data were analyzed according to age, sex, and time of
      admittance. RESULTS: The five most frequently encountered diseases in elderly
      patients were eczematous dermatitis, fungal infections, pruritus, and bacterial
      and viral infections. The most common disorders in males were fungal, bacterial,
      and viral infections, disorders of the feet, cutaneous ulcers, and vesiculo
      bullous diseases, whereas, in females, they were immune-rheumatologic diseases
      and disorders of the mucous membranes. The five most frequently encountered
      diseases were significantly different in geriatric age subgroups. In the younger
      age group, pruritus, disorders due to sun exposure, and precancerous lesions and
      skin carcinomas were less common, whereas eczematous dermatitis was more common.
      The frequencies of some diseases showed significant seasonal variations.
      Infestations were more common in spring and summer, fungal infections were more
      common in summer but less so in winter, pruritus was more common in autumn but
      less so in spring, disorders due to sun exposure were more common in spring, and
      benign neoplasia were more common in autumn. In 2003, benign neoplasia,
      precancerous lesions and skin carcinomas, and immune-rheumatic disorders were
      more common, but vesicular and bullous diseases, fungal infections, and cutaneous
      lymphomas were less common when compared with the year 1999. CONCLUSIONS: This
      study provides important data on the frequency of dermatologic diseases in
      elderly patients, and shows variations in the frequency depending on age, gender,
      and season. We believe that this study will create awareness about the extent and
      patterns of dermatologic problems in geriatric patients.

PMID- 16796626
TI  - Pulmonary involvement in Sweet's syndrome: a case report and review of the
      literature.
AB  - Pulmonary involvement in Sweet's syndrome (SS) is rare. We report a case of SS
      with severe respiratory involvement responding to corticosteroid therapy. A 82
      year-old man presented fever of 39 degrees C associated with cough and dyspnea,
      and crackles in the left lung. The infection work-up was negative. Chest X-ray
      showed cardiomegaly and left lower lobe pulmonary infiltrates. Pulmonary signs
      did not improve on treatment with antibiotics, and after 1 week maculopapular
      lesions appeared, localized on the knees, the periombilical area and the back.
      The antibiotics were changed without improvement. A skin biopsy revealed
      infiltration by neutrophilic granulocytes and marked edema in the dermis,
      consistent with SS. The patient's condition progressively worsened, requiring
      high oxygenotherapy, and he was transferred to an intensive care unit. Chest X
      ray revealed an important alveolar and interstitial syndrome. Bronchoalveolar
      lavage found 170 leukocytes with 30% neutrophils (N < 5%), 7% lymphocytes and 63%
      macrophages. A search for bacteria, viruses or parasites in bronchoalveolar
      lavage was negative. The patient was treated with antibiotics, a high dose of
      furosemide and steroids for 4 days. Because the patient improved dramatically
      within 5 days, with a negative infection work-up and a dramatic decrease of C
      reactive protein, the antibiotics were stopped. Steroids were secondarily tapered
      very slowly. A chest computed tomography (CT) scan showed a substantial
      improvement of pulmonary lesions. We also review the 22 cases of pulmonary
      involvement of SS reported in the literature.

PMID- 16796627
TI  - Association of penile lichen sclerosus and oncogenic human papillomavirus
      infection.
AB  - BACKGROUND: Data on the prevalence of human papillomavirus (HPV) infection in
      patients with penile lichen sclerosus (LS) are scant and controversial. AIM: To
      investigate the prevalence of HPV infections in patients with penile LS. METHODS:
      HPV infection was assessed by polymerase chain reaction (PCR) in paraffin
      embedded penile biopsies obtained from the glans or inner foreskin of 46 adult
      patients with penile LS, and in brush cytology smears of penile healthy mucosa
      from an equal number of randomly selected control males matched for age.
      Statistical evaluation was performed using conditional logistic regression
      analysis. RESULTS: PCR disclosed the presence of HPV infection in 17.4% of LS
      patients (HPV 16, six cases; HPV 18, one case; HPV 45, one case). Amongst the
      controls, HPV infection occurred in 8.7% of patients (HPV 16, two cases; HPV 53,
      one case; HPV 70, one case). Statistical regression analysis confirmed that the
      rate of HPV infection was higher amongst patients with genital LS than amongst
      healthy controls [odds ratio (OR), 2.55; 95% confidence interval (CI), 0.73
      8.89]. CONCLUSIONS: Infection with oncogenic "high-risk" HPV types in patients
      with genital LS may enhance the risk of penile cancer arising on LS.

PMID- 16796628
TI  - Smallpox vaccination site complications.
AB  - The typical resolution of the smallpox vaccination site is a smooth scar, a
      sequela that is discussed during prevaccination counseling. In addition, other
      types of lesion may develop at the scar site, including short- or long-term
      benign and malignant changes, as reviewed below. Although current recommendations
      do not discuss potential scar complications or scar surveillance, healthcare
      providers would benefit from an awareness of these potential complications, and
      should consider periodic scar surveillance as part of a general physical
      examination.

PMID- 16796630
TI  - Netherton syndrome: a case report and review of the literature.
AB  - Netherton syndrome is a rare disorder inherited in an autosomal recessive pattern
      consisting of ichthyosiform dermatosis, hair shaft abnormalities (trichorrhexis
      invaginata), and an atopic diathesis. Patients with Netherton syndrome have been
      found to have a mutation on chromosome 5q32 in a gene named SPINK5 (serine
      protease inhibitor, Kazal type-5), which encodes an inhibitor of serine proteases
      called LEKTI. We report a female patient with previously undiagnosed Netherton
      syndrome who presented to participate in a clinical research trial investigating
      the benefit of topical tacrolimus 0.03% ointment [Protopic (Fujisawa
      Pharmaceutical Co. Ltd., Japan)] for the treatment of atopic dermatitis. This
      patient was confirmed to have a gene mutation in SPINK5. Current literature
      suggests a relative contraindication for use of topical tacrolimus in patients
      with Netherton syndrome owing to concern for increased systemic absorption of the
      drug. Our patient was not able to tolerate topical tacrolimus owing to local
      irritation, and did not derive any benefit from therapy. Though rare, when
      evaluating patients with a possible diagnosis of atopic dermatitis, an index of
      suspicion for Netherton Syndrome must be maintained. History and overall clinical
      findings, especially in regards to examination of the hair, will aid in
      diagnosis.

PMID- 16796629
TI  - Use of etanercept in human immunodeficiency virus (HIV) and acquired
      immunodeficiency syndrome (AIDS) patients.
AB  - BACKGROUND: Etanercept (Enbrel, Amgen, Thousand Oaks, CA), a soluble p75 tumor
      necrosis factor receptor:FC (TNFR:FC) fusion protein for plasma cytokines,
      specifically tumor necrosis factor-alpha (TNF-alpha), is used in the treatment of
      immune-mediated rheumatic diseases. To our knowledge, the use of etanercept in
      patients with human immunodeficiency virus (HIV) and acquired immunodeficiency
      syndrome (AIDS) is relatively uncommon. OBJECTIVE: The main purpose of this short
      review is to examine the safety of etanercept in patients with HIV/AIDS. METHODS:
      A Medline search was conducted using the keywords etanercept and HIV and/or AIDS
      for any published articles between 1966 to the present (September 2004). RESULTS:
      A case report, one case series, and one clinical trial pertained to the use of
      etanercept in HIV patients. No reports were found on the use of etanercept in
      AIDS. In addition, two case reports were found documenting the use of infliximab
      in HIV patients. DISCUSSION: Preliminary reports indicate that the administration
      of etanercept does not appear to increase the morbidity or mortality rates in
      HIV. The inhibition of TNF-alpha may actually improve the symptoms of HIV/AIDS
      associated aphthous ulcers, cachexia, dementia, fatigue, and fever, as well as
      help manage concomitant rheumatic diseases and psoriasis. CONCLUSION: The use of
      etanercept shows promise for applications in disease management in patients with
      HIV/AIDS. Continued research efforts are necessary to establish the long-term
      safety and efficacy of etanercept and other biologic agents in this patient
      population.

PMID- 16796631
TI  - Correlation of clinical features and skin barrier function in adolescent and
      adult patients with atopic dermatitis.
AB  - BACKGROUND: Xerotic changes in atopic skin are considered to be related to a
      decrease in the water permeability barrier. Whether abnormal skin barrier
      function is the main cause of atopic dermatitis (AD) or a secondary change of the
      disease is still controversial. Noninvasive bioengineering methods, including the
      measurement of the transepidermal water loss (TEWL) and water capacitance, have
      been commonly used to evaluate skin barrier function. AIM: To evaluate the
      correlation between the clinical features of each evaluation site (severity of
      AD) and skin barrier function. METHODS: TEWL, capacitance, and pH were checked on
      five evaluation sites: postauricle, forearm, abdomen, thigh, and popliteal fossa.
      The subjects included 25 patients, both adolescents and adults, with AD and 25
      age-matched normal controls. The clinical severity, from 0 (no clinical
      manifestation) to 3 (severe), was also scored for erythema,
      induration/papulation, lichenification, and xerosis on each evaluation site of
      the AD patients. RESULTS: Based on the data, we found that the clinical severity
      score was correlated with TEWL and capacitance in more than one-half of the
      evaluation sites. Erythema and induration/papulation showed a statistically
      significant correlation with TEWL in most cases (P < 0.05, four sites).
      Lichenification and xerosis showed a significant correlation with capacitance in
      most cases (P < 0.05, four sites). In most cases, severity scoring of the
      clinical features did not show a significant correlation with skin pH. The
      patients showed higher TEWL and lower capacitance than normal controls (P < 0.05,
      all five sites). CONCLUSIONS: The results of our study suggest that skin barrier
      function, measured by TEWL and capacitance, and clinical severity show a
      statistically significant correlation in patients with AD.

PMID- 16796632
TI  - Sweet's syndrome from an Indian perspective: a report of four cases and review of
      the literature.
AB  - BACKGROUND: Sweet's syndrome or acute febrile neutrophilic dermatosis is not
      frequently reported from India. Four patients fulfilling clinico-pathologic
      criteria for Sweet's syndrome seen during May-August 2002 prompted us to review
      reports on Indian patients from the indexed literature. METHODS: A PubMed and
      IndMed search for Sweet's syndrome revealed 11 reports appearing between 1985
      2002 documenting 12 patients. The clinico-pathologic features, clinical course
      and treatment of all these 16 patients (including four new cases) were studied.
      RESULTS: The study comprised 12 females and four males between 35 days to 57
      years of age. There were four children of < 12 years. Ulcerated, crusted lesions
      in one and typical, erythematous, tender, papulo-nodulo-plaques and targetoid
      lesions with pseudovesiculation were observed in 13 other patients particularly
      involving head, neck and upper limbs. Extracutaneous Sweet's syndrome manifesting
      as gingival hyperplasia and myositis was seen in one patient each. All had
      simultaneous onset of cutaneous lesions, fever, headache and malaise. Ocular
      involvement was observed in four patients only. Associated hematoligic disorders
      recorded were myelodysplasia in three, polycythemia vera in one and leukemia in
      three patients respectively. Two of these patients had treatment with all
      transretinoic acid and low-dose cytosine-arbinoside before onset of Sweet's
      syndrome. One patient each had symptoms of upper respiratory tract infection and
      history of minor injury prior to cutaneous lesions. Another patient had pregnancy
      induced self-limiting Sweet's syndrome. Leukocytosis was present in 11 patients.
      Three of four new patients had positive tests for antistreptolysin-O and C
      reactive protein. Characteristics histologic features were recorded in specimens
      of all patients. Eleven patients responded to systemic corticosteroids. Colchicin
      or potassium iodide were effective in one patient each. CONCLUSION: The overall
      clinico-pathologic and therapeutic spectrum of Sweet's syndrome in Indian
      patients does not appear to be different from its established picture.

PMID- 16796633
TI  - Naproxen-induced lichen planus: report of 55 cases.
AB  - BACKGROUND: Clinical and histopathological differential diagnosis is usually
      impossible in drug-induced lichen planus (LP) and idiopathic LP. Naproxen is a
      nonsteroidal anti-inflammatory drug, which is widely used for its analgesic,
      antipyretic and anti-inflammatory effects. To the best of our knowledge, two case
      reports on naproxen-induced LP have been reported. METHODS: Fifty-five patients
      with LP, and a history of naproxen intake before their eruption, were
      investigated. RESULTS: Twenty-five patients (45.5%) had a history of naproxen
      intake prior to their eruption without any other medication. Twelve patients
      (21.8%) had a history of simultaneous use of naproxen with other drugs that were
      reported as inducers of LP. Eighteen patients (32.7%) had given a history of
      using naproxen together with drugs that had not been previously reported as
      inducers of LP. Moreover, in 42 patients, eruptive-type LP development after
      naproxen intake, is an interesting observation. New lesions were not observed
      after the cessation of naproxen intake in any of the patients. CONCLUSION:
      Naproxen might be accepted as an important inducer for LP, especially for the
      eruptive form.

PMID- 16796634
TI  - Clinical features of Behcet's disease in children.
AB  - BACKGROUND: Behcet's disease (BD) is a systemic inflammatory vasculitis of young
      adults with unknown etiology. OBJECTIVE: The aim of this study was to determine
      the clinical features and outcome of BD in childhood. PATIENTS AND METHODS:
      Seventeen patients with BD within a pediatric age group were studied since 1997.
      RESULTS: Boys : girls ratio was 12:5. Familial cases were very frequent (45%).
      Oral aphthous ulcers were present in all patients (100%), genital aphthous ulcers
      were present in 16 (94%), ocular lesions in 4 (24%), erythema nodosum in 3 (18%),
      papulopustules in 8 (47%), joint symptoms in 13 (76%), mild gastrointestinal
      symptoms in 2 (12%), neurological involvement in 2 (12%), positive pathergy
      reactions in 13 (76%), and thrombophlebitis in 1 (6%). We used colchicine,
      systemic corticosteroids, cyclosporine, nonsteroidal anti-inflammatory drugs,
      sulfasalazine, and topical agents for the treatment of children with BD.
      CONCLUSION: The findings of BD in children are similar as in adults, but the
      frequency of familial cases is significantly higher.

PMID- 16796635
TI  - Lupus erythematosus profundus in black South Africans.
AB  - BACKGROUND: Lupus erythematosus profundus (lupus panniculitis) is a rare variant
      of lupus erythematosus with predominant involvement of the subcutaneous tissue.
      There are only a few reported series of patients with this condition; none in
      individuals of African ancestry. The aim of the study was to evaluate clinical,
      histopathological and laboratory findings in black South African patients with
      lupus profundus. PATIENTS AND METHODS: Ten prospectively observed patients were
      studied. Skin biopsies were performed, and several laboratory tests routinely
      employed in patients with lupus erythematosus were carried out. All patients were
      followed up for at least a year and their response to treatment was assessed.
      RESULTS: All patients were females. Mean age at diagnosis was 28.5 years. Face
      was the most common site of involvement. In five patients, the periorbital edema
      was the initial manifestation. Only one patient had systemic lupus, and three
      patients also showed lesions of discoid lupus. In only 30% of the patients were
      the ANA titers greater than 1 : 80, and positivity in other lupus tests was rare
      and inconsistent. In general, patients responded to antimalarials and/or systemic
      corticosteroids. CONCLUSION: African patients with lupus profundus when compared
      with other series comprising Asian and white patients showed greater frequency of
      periorbital edema as the initial manifestation. Review of the literature
      disclosed that this subset of lupus profundus appears to have a more benign
      course.

PMID- 16796636
TI  - Clinical and histological characteristics of poroid neoplasms: a study of 25
      cases in Taiwan.
AB  - BACKGROUND: Eccrine poroma (EP) are relatively common benign eccrine neoplasms.
      Other poroid neoplasms (PNs), namely hidroacanthoma simplex (HS), dermal duct
      tumor (DDT), and poroid hidradenoma (PH), are seldom reported. METHODS: Among 18
      653 biopsy specimens received from January 1988 to October 2003, we found 25 PNs
      (0.134%). We conducted retrospective analysis and obtained clinical and
      histopathological information. RESULTS: There were 16 EP, 3 HS, 4 PH, and 2 PH
      coexisting with either HS or EP. No DDT was found. More than half of PNs
      presented as red-color neoplasms, but none were diagnosed correctly on clinical
      grounds alone. The most common preoperative diagnoses were pyogenic granuloma or
      soft fibromas. Most EPs were located on hair-bearing regions of the limbs (37.5%)
      and trunk (25%), instead of soles (18.8%) and palms (6.3%). Three HS showed no
      cuticular cell, but had monomorphic poroid cells. Most EPs (10/16) were composed
      of both poroid and cuticular cells. All PH were composed of cuticular and poroid
      cells. Horn cysts were found in three cases (12%). Most PNs (16/25) contained
      clear cells. CONCLUSIONS: PNs are sudoriferous tumors that may vary considerably
      in clinical expression. EP, about 64% (16/25) of PNs in our series, was the most
      common. PH incidence is probably underestimated in the literature. We found six
      PHs in 25 PNs. Histopathologically, it is not justified to exclude PN diagnosis
      by noticing horn cysts. It was uncommon for two or three subtypes of PN to occur
      in a single lesion.

PMID- 16796637
TI  - Lesson from performing SCORADs in children with atopic dermatitis: subjective
      symptoms do not correlate well with disease extent or intensity.
AB  - BACKGROUND: Atopic dermatitis (AD) is a distressing disease associated with
      pruritus and sleep disturbance. It is not known how well these symptoms correlate
      with the extent and intensity of eczematous involvement. We evaluated whether:
      (i) the level of sleep loss correlates with pruritus and (ii) the level of
      pruritus correlates with the extent or severity of AD in children according to
      the SCORing Atopic Dermatitis (SCORAD) index. METHOD: Patients with AD younger
      than 18 years old were recruited from the pediatric dermatology clinic of a
      university teaching hospital, and AD severity was evaluated by the SCORAD index.
      RESULTS: One hundred and eighty-two Chinese children with AD (107 boys and 75
      girls) [mean (SD) age of 9.6 (4.2) years] were recruited. Their mean (SD) overall
      SCORAD was 30.1 (19.2). Sleep loss was strongly correlated with pruritus (r =
      0.57, P < 0.001). However, the two subjective symptoms were only weakly
      correlated with the objective signs (extent and intensity) of AD. The
      correlations between pruritus and extent and intensity were 0.42 (P < 0.001) and
      0.38 (P < 0.001), respectively, and the correlations between sleep loss and
      extent and intensity were 0.38 (P < 0.001) and 0.34 (P < 0.001), respectively.
      CONCLUSION: We speculate that the lack of a better correlation was either because
      pruritus and sleep loss as reported by parents were imprecise, or that mechanisms
      other than disease extent or severity are responsible for the pathogenesis of
      these subjective symptoms.

PMID- 16796638
TI  - Quality of life in patients with atopic dermatitis: impact of tacrolimus
      ointment.
AB  - BACKGROUND: Atopic dermatitis (AD), a significant problem in Japan, has a major
      impact on health-related quality of life (QOL). The development of steroid phobia
      in patients with AD may restrict the therapeutic options available to these
      patients. Tacrolimus ointment is a safe and effective nonsteroid treatment for
      AD. It may be an appropriate alternative for patients with AD and steroid phobia.
      The aim of this study was to determine the impact of AD on QOL and to investigate
      the effect of tacrolimus ointment on QOL in patients with steroid phobia.
      METHODS: Firstly, QOL scores were investigated in patients with AD and steroid
      phobia using the World Health Organization Quality of Life instrument, WHOQOL-26,
      and were compared with QOL scores from a previous study in volunteers from Tokyo,
      Japan. Secondly, patients with steroid phobia received tacrolimus ointment
      treatment for 12 weeks. Quality of life scores were assessed using WHOQOL-26 at
      baseline and study end. RESULTS: The overall mean QOL score of 106 patients with
      AD was significantly lower than that of 708 volunteers (3.1 +/- 0.5 vs. 3.3 +/-
      0.5, P < 0.001). The overall QOL score improved from 2.9 +/- 0.4 at baseline to
      3.3 +/- 0.4 following 12 weeks' tacrolimus ointment treatment in 35 patients with
      AD and steroid phobia (P < 0.001). CONCLUSIONS: Atopic dermatitis significantly
      lowers QOL. Tacrolimus ointment is associated with a significant improvement in
      QOL in patients with steroid phobia, indicating that it is an effective
      alternative to topical corticosteroids in these patients.

PMID- 16796639
TI  - Progressive macular hypomelanosis in Singapore: a clinico-pathological study.
AB  - INTRODUCTION: Progressive macular hypomelanosis (PMH), a condition of uncertain
      etiology, is characterized by asymptomatic hypopigmented macules predominantly
      located on the trunk. To date, there are no reports from South-East Asia
      concerning this condition. We sought to record the clinical features of PMH in
      Asian patients, identify etiologic factors, and study the structural and
      ultrastructural features of melanocytes in this disorder. METHODS: Patients who
      presented to the National Skin Center with acquired, hypopigmented macules on the
      trunk, without a history of inflammation or infection, were recruited.
      Erythrocyte sedimentation rate (ESR), complete blood count, fasting blood
      glucose, liver function tests, skin scrapings for fungi, and skin biopsy
      specimens (from lesional and normal skin) were obtained. Biopsies were stained
      with hematoxylin and eosin (H&E), Fontana Masson, an immunohistochemical panel
      for identification of melanocyte differentiation antibodies (HMB 45, Melan A, and
      S100) and CD 68. Electron microscopy (EM) was also performed. The patients were
      evaluated every 3 months. RESULTS: During a 9 month period, eight patients (all
      Chinese) presented with hypopigmented, ill-defined, confluent macules involving
      the lower aspect of the trunk. There were four men and four women, and the mean
      age was 25.9 years (range 19-45 years). Skin scrapings were negative for fungi
      and laboratory tests were normal. Microscopic evaluation of skin biopsy specimens
      showed reduced pigmentation of lesional as compared with normal appearing skin,
      but H&E-stained sections revealed only minimal histologic differences between
      lesional and normal skin. EM demonstrated a statistically significant (P = 0.047,
      Wilcoxon Signed Rank Test, Wilcoxon 95% CI 0.02-0.62) higher ratio of stage IV
      and late stage III (dark) melanosomes in normal vs. lesional skin. CONCLUSIONS:
      PMH may occur among young adults in Singapore. Its etiology is uncertain. The
      melanin content of lesional skin appears to be less than that in normal sites. EM
      shows a higher ratio of immature melanosomes in lesional vs. normal skin.

PMID- 16796640
TI  - Healing effect of Pilocarpine gel 4% on skin lesions of pemphigus vulgaris.
AB  - BACKGROUND: The high rate of morbidity and mortality resulting from long-term use
      of corticosteroids in pemphigus vulgaris (PV) warrants discovery of a new
      treatment strategy. Based on a new theory on the pathophysiology of PV,
      cholinomimetics can block the process of blister formation. AIMS: This study was
      conducted to evaluate the clinical effectiveness of Pilocarpine gel in the
      treatment of skin lesions of PV. METHODS: In a double-blind, placebo-controlled
      study, three PV patients with a total of 64 skin lesions were treated by either
      Pilocarpine or placebo gel. After 15 days of treatment an epithelialization index
      of the two groups was compared. RESULTS: The mean of the epithelialization index
      in skin lesions that received Pilocarpine was significantly higher than that of
      the placebo group (40.3 +/- 1.7 vs. 24.4 +/- 3.3, P < 0.001). CONCLUSIONS:
      Pilocarpine gel effectively treats PV.

PMID- 16796641
TI  - Autologous melanocyte transfer via epidermal grafts for lip vitiligo.
AB  - BACKGROUND: Vitiligo of the lips is a common concern of great psychologic
      consequence. Medical therapies are often ineffective due mainly to the absence of
      hair follicles. The transfer of melanocytes or melanocyte-bearing skin by a
      surgical procedure may repigment this condition. Only a few surgical modalities
      have been successful in this "difficult to treat" site. OBJECTIVE: To assess the
      effectiveness of autologous melanocyte transfer by epidermal grafts for lip
      vitiligo and to review the literature on the surgical correction of lip vitiligo.
      METHODS: Twenty-six vitiligo patients (20 women and six men; age range, 13-43
      years; mean, 26.8 years) having 31 affected lips with stable disease were
      included in the study. The suction blisters were raised using our own modified
      device on the lateral aspect of the thigh. The roofs of the blisters were
      transferred to the dermabraded recipient area. The dressing, together with the
      grafts, was removed on day 8. Patients were given photochemotherapy for 6 weeks.
      In addition, meta-analysis of the published literature on the surgical management
      of lip vitiligo was also performed. RESULTS: Complete repigmentation was observed
      in 27 of the 31 lip areas (87%) in 23 of 25 patients (92%) in whom a follow-up
      for 6 months or more was available. Complications observed were persistent
      hyperpigmentation in 12 lips and reactivation of herpes in one patient. Minimal
      hyperpigmentation was seen in most of the remaining lips. The results of the meta
      analysis revealed that the success rate varies from 32.5% to 100% with various
      surgical procedures. CONCLUSION: Autologous melanocyte transfer is an effective
      and safe therapeutic option for stable vitiligo of the lips. It is cosmetically
      more acceptable, as there is no abnormal keratinization, which is a problem
      associated with dermo-epidermal grafts.

PMID- 16796642
TI  - Treatment of diffuse cutaneous leishmaniasis with miltefosine: a case report.
AB  - BACKGROUND: A 31-year-old man who has suffered since age 3 from diffuse cutaneous
      leishmaniasis (DCL), a disease with profound physical and psychosocial
      repercussions and no effective treatment at present, was treated with
      miltefosine. METHODS: The patient was treated for 120 days, 100 mg/day for 1
      week, then 150 mg/day subsequently. RESULTS: Lesions were free of parasites at 43
      days, and no signs of infiltration were present at day 76. No adverse side
      effects were observed. CONCLUSIONS: The dramatic clinical effect of miltefosine
      in this patient appears to fully justify further evaluation of this experimental
      therapy in DCL.

PMID- 16796643
TI  - Tumbu larvae do not have abdominal hooklets and can be easily extracted.

PMID- 16796644
TI  - Familial desmoplastic trichoepithelioma.

PMID- 16796645
TI  - Skin manifestations with Rotavirus infections.
AB  - Rotavirus infection is one the most frequent cause of diarrhea among infants and
      children. Although it is not associated to specific dermatologic clinical
      pictures, recently, different clinical manifestations have been reported in
      association with this infection. They include exanthema, Gianotti-Crosti
      syndrome, and Acute Infantile Hemorrhagic Edema. The condition can be diagnosed
      microbiologically with stool cultures. The prognosis is excellent in healthy,
      immunocompetent individuals.

PMID- 16796646
TI  - Eccrine squamous syringometaplasia mimicking a herpetic infection.

PMID- 16796647
TI  - Smallpox vaccination site reactions: two cases of exaggerated scarring and a
      brief review.

PMID- 16796648
TI  - Cutaneous presentation on the eyelid of primary, systemic, CD30+, anaplastic
      lymphoma kinase (ALK)-negative, anaplastic large-cell lymphoma (ALCL).
AB  - AIM: To report an unusual case of cutaneous presentation on the eyelid of
      systemic (or nodal), CD30+, anaplastic large-cell lymphoma (ALCL). METHODS: A 39
      year-old man presented with a rapidly growing exophytic mass on the left upper
      eyelid, with a protuberant, ulcerated aspect and with discharge. The patient
      showed lymph node involvement 3 months after the appearance of the lesion on the
      eyelid (the lesion itself appeared 1 week before examination). RESULTS: The
      histopathologic and immunohistochemical diagnosis was ALCL, T-cell phenotype,
      strongly positive for CD43 and CD30, and negative for CD3, anaplastic lymphoma
      kinase (ALK), and B-cell antigens. Treatment was by radiotherapy and, later,
      chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisolone, CHOP)
      for skin recurrences and lymphadenopathies over 5 years. There has been no
      recurrence for more than 6 years. CONCLUSIONS: Primary, systemic, CD30+, ALK
      negative, ALCL presentations generally have a poor prognosis and tend to occur in
      older individuals, although the clinical outcome is highly variable and difficult
      to predict in individual cases. Only three cases of ALCL have been described in
      the ocular adnexae and none was ALK-negative.

PMID- 16796649
TI  - Dissociative identity disorder presenting as dermatitis artefacta.
AB  - Dermatitis artefacta is a rare psychiatric condition characterized by rubbing of
      skin blisters and denial of self-infliction. Dissociation may be comorbid with
      self-injurious behavior. A background of emotional disturbances during formative
      years and in later life often results in feelings of isolation and insecurity,
      which can lead to dissociation as a primary defense mechanism used to overcome
      traumatic events. In this case report, we describe a female patient with
      dermatitis artefacta associated with dissociative identity disorder. The patient
      was a 14-year-old girl. Multiple large, deep ulcerations with unnatural shapes
      were seen on her left forearm. The ulcerations were thought to be self-inflicted.
      Psychiatric examination revealed that she had a different identity, and inflicted
      the lesions when this was assumed. This case leads us to suggest that patients
      with dermatitis artefacta might have comorbid dissociative experiences, which
      cannot be identified easily.

PMID- 16796650
TI  - Isotretinoin--unapproved indications/uses and dosage: a physician's reference.

PMID- 16796651
TI  - Precancerous skin lesions in patients treated at the Clinic for
      Dermatovenereologic Diseases in Novi Sad.

PMID- 16796652
TI  - Mesalamine may be preferable to sulfasalazine in dermatologic therapeutics.

PMID- 16796654
TI  - A case of rhinocerebral zygomycosis caused by Rhizopus arrhizus.

PMID- 16796655
TI  - Spontaneous complete regression of multiple Bowen's disease in the web-spaces of
      the feet.

PMID- 16796656
TI  - Perspectives and experiences of homeless young people.
AB  - AIM: This paper reports a study describing the experiences and perspectives of
      homeless young people as research participants. BACKGROUND: Worldwide, homeless
      young people are an especially vulnerable group due to their age, socio-economic
      disadvantage, and stigmatized status, and can suffer from human rights abuses.
      Researchers and advocates have noted that we know relatively little about the
      effects of research participation on adolescents in general, and much less about
      marginalized adolescents such as homeless young people; nor do we know about
      their perceptions and experiences as research participants. There is a lack of
      studies reported to help guide the ethical conduct of research with homeless
      young people. METHODS: Individual interviews with 30 street and clinic-based
      homeless young people aged 15-23 years and two focus groups with a total of 13
      additional homeless young people were conducted in a large West-coast city in the
      United States of America. The study took place between January and June 2003.
      Interviews and focus groups were tape-recorded, transcribed, preliminarily coded,
      with final coding crosschecked and verified with a second researcher. FINDINGS:
      The majority of young people reported positive experiences as research
      participants in the past. None reported coercive research experiences; however,
      many stated that they would have liked more information about how the data they
      provided would be used by the researchers. All participants reported that it was
      important to be provided with research incentives, and thought that small
      monetary or pre-paid phone cards were appropriate incentives. They did express
      concerns that larger research incentives could be coercive and harmful for some
      homeless young people. CONCLUSION: Researchers working with homeless young people
      should seek greater input from them on the overall design of the study,
      especially concerning the appropriate use of research incentives.

PMID- 16796657
TI  - Physical activity and physical self-concept: comparison between children with and
      without asthma.
AB  - AIM: This paper reports a study comparing levels of physical activity and
      physical self-concepts between children with and without asthma. BACKGROUND:
      Childhood asthma has become one of the world's most prevalent chronic illnesses.
      Its symptoms are thought to prevent children from participating in some forms of
      physical activity. However, asthma treatment guidelines are increasingly
      suggesting that children with asthma can participate in the same physical
      activities as healthy children for the same reasons-- to promote normal growth,
      physical development and psychological health. METHOD: Between October 2001 and
      May 2002, 120 children between the ages of 9 and 11 with mild and moderate asthma
      were recruited from three paediatric asthma clinics in Taiwan, and 309 non
      asthmatic children in the same age group were selected from four elementary
      schools in Taiwan's three largest cities. Participants were asked to record
      physical activity levels for 3 days out of the past 7 days and to fill out a 29
      item Physical Self-Concept Inventory. Physical activities were classified as
      moderate-to-vigorous physical activity or vigorous physical activity. Physical
      self-concept was measured in terms of perceived flexibility, endurance,
      appearance, agility, obesity and strength. RESULTS: Asthma was the primary factor
      determining vigorous physical activity levels, but gender was the primary factor
      determining physical self-concept, especially in terms of endurance, obesity and
      strength. No statistically significant relationships were noted between asthma
      and gender in terms of effects on physical activity and physical self-concept.
      CONCLUSIONS: Asthma interferes with children's ability to participate in vigorous
      physical activity but not in moderate-to-vigorous physical activity. Gender
      determines primary differences in physical self-concept. Appropriate exercise
      recommendations are necessary to encourage children with asthma to engage in
      vigorous physical activity for normal growth.

PMID- 16796658
TI  - Predictors of exercise participation in female hospital nurses.
AB  - AIM: This paper presents a study to ascertain the relationship between exercise
      participation and selected personal factors, perceived benefits of and barriers
      to exercise, perceived self-efficacy, perceived social support, job demands and
      motivation. Factors that were the best predictors of exercise participation among
      Thai female hospital nurses were examined. BACKGROUND: Although current evidence
      demonstrates positive outcomes from participation in exercise, most individuals
      do not engage in regular exercise. Perceptions of benefits have been shown to
      facilitate adoption of exercise. If individuals do not perceive their health to
      be threatened, they may not see the need to exercise, even though they may
      believe that exercise improves health. Perceived barriers to exercise, including
      work, lack of social support, inaccessibility of exercise facilities, the cost of
      exercise, lack of energy and health reasons also have been shown to affect
      participation in exercise. Most studies have found that perceived self-efficacy
      and social support were statistically significant predictors of exercise
      participation, especially social support from family and friends. METHODS: A
      correlational cross-sectional study was conducted at a hospital located in
      Thailand. Social cognitive theory and the Health Promotion Model guided this
      study. Thai language translations of the questionnaire were distributed to all
      Thai female nurses. The data were collected in 2002. RESULTS: The response was
      87% and resulted in 970 completed questionnaires. There was a statistically
      significant relationship between exercise participation and the set of selected
      personal factors, perceived benefits of and barriers to exercise, perceived self
      efficacy, and perceived social support (r(2) = 0.17, P < 0.0001). The addition of
      job demands and its interactions did not contribute statistically significantly
      to the prediction of exercise participation. The addition of motivation
      contributed statistically significantly to the prediction of exercise
      participation, t(947, 0.975) = 2.81, P < 0.01 (two-tailed). Not all variables
      included in the models were statistically significant independent predictors of
      exercise participation. CONCLUSIONS: The results indicate that increased exercise
      participation is dependent on the nurses' perceptions of exercise, self-efficacy
      and social support as well as their motivation to participate in exercise.
      Occupational variables, such as occupational stress and work assignment, should
      be investigated in future studies, to examine their influence on nurses'
      participation in exercise.

PMID- 16796659
TI  - Nutritional counselling: an intervention for HIV-positive patients.
AB  - AIM: This paper reports an investigation of the effectiveness of nutritional
      counselling as an intervention to improve health outcomes for HIV-positive
      patients in Ghana, West Africa. BACKGROUND: In Ghana, like many developing
      countries, more patients with HIV and AIDS die because of their poor nutritional
      status than from the disease itself. With the lack of highly active anti
      retroviral therapy for most HIV-infected patients in developing countries,
      nutritional counselling about high protein diet can be an essential intervention
      to reduce weight loss and improve weight gain and survival outcomes. METHOD: We
      used secondary-analytic data collected in summer 2003. Recorded monthly weights
      of HIV-positive patients were obtained and analysed for 25 people, whose ages
      ranged from 21 to 60 years, with a mean of 39.4 years (sd = 10.13). RESULTS: HIV
      positive patients responded favourably to nutritional counselling about protein
      dietary intake as an intervention to improve weight gain. Repeated measures
      showed a statistically significant weight gain (P = 0.008). CONCLUSION: In the
      absence of anti-retroviral therapy, high protein nutrition can be an effective
      intervention for HIV-positive patients in developing countries. The health and
      nutritional status of the patients can be improved through nutritious food,
      allowing them to lead longer and better quality lives.

PMID- 16796660
TI  - Women and abortion: the past reaches into the present.
AB  - AIM: This paper reports a study of women's responses to abortion over an extended
      time. BACKGROUND: Most studies of postabortion responses do not portray what
      women experience over an extended time period, since many only use a 24 month
      follow-up period. Results from previous studies indicate that women have thoughts
      about their abortion that they suppress or find intrusive. METHOD: Sixteen women
      who had chosen to terminate a pregnancy for non-medical reasons at least 15 years
      previously were interviewed during the years 1999-2001. This phenomenological
      study revealed their responses to and thoughts about their abortion(s). FINDINGS:
      Each of the women spoke about thinking of their abortion(s) at varied times. The
      abortion(s) was/were not a time-limited event; instead thoughts, emotions, and
      insights about the meaning of these experiences were on-going, as life events
      unfolded. The past reached into the present in varied ways and at unplanned
      times. Difficulties with subsequent pregnancies, life milestones, and mundane
      occurrences involving friends' children were common triggers for recurring
      thoughts about past abortions. These recurrent thoughts had characteristics of
      avoidance or suppression and intrusion. CONCLUSION: When taking an obstetric
      history, nurses and midwives should be sensitive when inquiring about
      discrepancies between the number of times a woman has been pregnant and the
      number of living children. Opportunity should be given for a woman to discuss in
      a safe, non-judgmental environment any emotions or thoughts she may express.
      Providers of women's healthcare services must reflect about ways to reassure
      women of the common nature of recurrent thoughts and the spectrum of emotional
      responses that, even years later, is normal.

PMID- 16796661
TI  - Influence of traditional Chinese beliefs on cancer screening behaviour among
      Chinese-Australian women.
AB  - AIM: This paper reports a study exploring how traditional Chinese life
      philosophy, including fatalism, influences understanding of the concepts of
      health and illness, and the impact of these concepts on cancer screening
      behaviour. BACKGROUND: The language of risk is central to contemporary Western
      understanding of health and illness. Women aged over 50 years are considered at
      risk of developing breast cancer and are highly recommended to undergo regular
      mammographic screening. However, screening rates among Chinese women are
      consistently lower than for most other groups. METHODS: In-depth interviews, in
      Cantonese, were conducted with a convenience sample of 20 Chinese-Australian
      women, and the data analysed thematically, using case summaries, coding and
      matrix tables. The data were collected in 2001. FINDINGS: The findings revealed
      that when dealing with cancer prevention, Chinese-Australian women are heavily
      influenced by cultural traditions related to the life-cycle and disease
      prevention. Informants believed that contracting disease, including cancer, is
      inevitable and that there is no way to prevent it. Fatalism appears to be a
      significant barrier to their participation in cancer screening services.
      CONCLUSION: Our findings suggest that the effects of breast cancer screening and
      other health promotion programmes, which are general and do not take account of
      cultural variations may be compromised when it comes to cultural minorities. In
      the case of older Chinese-Australian women, breast cancer screening promotion
      programmes may overcome acceptance of fatalistic philosophy if they emphasize
      increased risk following immigration.

PMID- 16796662
TI  - Nurses' and patients' perceptions of expert palliative nursing care.
AB  - AIM: This paper reports a study of the perceptions of patients and nurses of
      palliative care and, in particular, the concept of the expert palliative nurse.
      BACKGROUND: Palliative care is a growing specialty and is practised globally.
      There is, however, limited information on patients' views about palliative care.
      While the idea of expertise in nursing is not new, few studies have explored the
      concept of the expert nurse in palliative care. Some evidence exists on
      palliative nurses' perceptions of their care, that it is supportive and involves
      maintaining therapeutic relationships with patients. Facing a terminal illness
      has been identified as a stressful and fearful experience that affects all
      aspects of life. It has also been revealed that dying patients may have unmet
      care needs, mainly in the areas of pain and symptom control, emotional support,
      and spending time alone. METHODS: A phenomenological study was carried out, using
      in-depth interviews and thematic content analysis. A convenience sample of 22
      Registered Nurses and 22 dying patients was interviewed in 1996-1997. FINDINGS:
      Dying patients had a desire to maintain independence and remain in control.
      Palliative care nurses experienced both effective and ineffective interpersonal
      communication, the building of therapeutic relationships with dying patients and
      attempting to control patients' pain and distressing symptoms. Patients and
      nurses agreed that the two most important characteristics of an expert palliative
      nurse were interpersonal skills and qualities such as kindness, warmth,
      compassion and genuineness. CONCLUSION: Although the study was conducted in the
      United Kingdom, the findings have relevance for palliative care practice globally
      in terms of dependence, issues of patient choice, nurses being interpersonally
      skilled and building therapeutic relationships with patients.

PMID- 16796663
TI  - Use of a simple relaxation technique in burn care: literature review.
AB  - AIM: This paper presents a literature review examining the implications of
      previous research in order to make evidence-based decisions about the possible
      use of breathing exercises with adult patients with burns for pain management
      during wound care. BACKGROUND: Adult patients with burns experience pain during
      wound care despite pharmacological interventions. Additional interventions are
      needed to improve the effectiveness of pain management. Relaxation techniques can
      be considered, for example breathing exercises, music and distraction. A simple
      breathing relaxation technique is especially relevant because it involves no
      risk, is easy and quick to learn, equipment does not need to be purchased and it
      can be employed immediately by the often exhausted and ill patient. However, the
      effect of breathing exercises on procedural pain during burn wound care has not
      been investigated. METHOD: The CINAHL, PubMed and Cochrane databases were
      searched in 2004 in order to answer two questions: are breathing exercises
      effective in the management of procedural pain in adult burn patients, and what
      are the implications of previous investigations for future research concerning
      pain reduction in adult patients with burns during wound care? Eleven papers were
      included in the review. FINDINGS: The effect of breathing exercises for pain
      management in patients with burns has not been investigated. Prior to undertaking
      an effect study, additional basic research is needed. The number of sessions
      necessary to learn to use the technique should be clarified. A valid and reliable
      instrument to assess relaxation must be developed. The adequacy of the proposed
      data collection procedure needs to be assessed. CONCLUSION: It is not possible at
      this time to base decisions about the use of breathing exercises during wound
      care in adult patients with burns on research specific to the procedure and
      patient group. The most suitable relaxation technique for future investigation is
      concentration on breathing, in combination with jaw relaxation.

PMID- 16796664
TI  - Living with early-stage dementia: a review of qualitative studies.
AB  - AIM: This paper presents a literature review whose aim was to provide better
      understanding of living with early-stage dementia. BACKGROUND: Even in the early
      stages, dementia may challenge quality of life. Research on early-stage dementia
      is mainly in the domain of biomedical aetiology and pathology, providing little
      understanding of what it means to live with dementia. Knowledge of the lived
      experience of having dementia is important in order to focus pro-active care
      towards enhancing quality of life. Qualitative research is fundamentally well
      suited to obtaining an insider's view of living with early-stage dementia.
      METHOD: We performed a meta-synthesis of qualitative research findings. We
      searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the
      references of pertinent articles, the references cited in a recently published
      book on the subjective experience of dementia, one thesis, and the journal
      Dementia. Thirty-three pertinent articles were identified, representing 28
      separate studies and 21 different research samples. Findings were coded, grouped,
      compared and integrated. FINDINGS: Living with dementia is described from the
      stage a person discovers the memory impairment, through the stage of being
      diagnosed with dementia, to that of the person's attempts to integrate the
      impairment into everyday life. Memory loss often threatens perceptions of
      security, autonomy and being a meaningful member of society. At early stages of
      memory loss, individuals use self-protecting and self-adjusting strategies to
      deal with perceived changes and threats. However, the memory impairment itself
      may make it difficult for an individual to deal with these changes, thereby
      causing frustration, uncertainty and fear. CONCLUSIONS: Our analysis supports the
      integration of proactive care into the diagnostic process, because even early
      stage dementia may challenge quality of life. Moreover, this care should actively
      involve both the individual with dementia and their family so that both parties
      can adjust positively to living with dementia.

PMID- 16796665
TI  - Evaluating STORM skills training for managing people at risk of suicide.
AB  - AIM: This paper reports a study evaluating the Skills Training On Risk Management
      (STORM) training initiative in three mental health services in the North-West of
      England, UK. BACKGROUND: Training for health workers has been widely advocated as
      a key route to suicide prevention. However, reports of evaluations are scarce in
      the literature. In previous research, we have demonstrated that the STORM
      intervention results in acquisition of new skills and can be disseminated in a
      community setting. METHOD: The training was delivered during a 6-month period in
      2002 by three mental health nurses who were seconded part-time to the project.
      The quantitative evaluation, which assessed change in attitudes, confidence,
      acquisition of skills and satisfaction, used a pretest/post-test design, with
      participants acting as their own controls. Qualitative interviews were conducted
      with a purposive sample of 16 participants to explore the impact on clinical
      practice, and with the three trainers at the end of the study. FINDINGS: Data
      from 458 staff members were collected during a 6-month period. Positive changes
      in attitudes and confidence were shown, but previous evidence of skill
      acquisition was not replicated. Qualitative interviews revealed important
      insights into changes in clinical practice, particularly for less experienced or
      unqualified nursing staff, but also concerns about the lack of an educational
      culture to foster and support such interventions in practice within the
      organizations. CONCLUSION: STORM training for the assessment and management of
      suicide risk is both feasible and acceptable in mental health trusts. However, we
      remain uncertain of its longer-term impact, given the lack of engagement of
      senior staff in the enterprise and the absence of linked supervision and support
      from the organizational management to reinforce skill acquisition and
      development. We consider that regular supervision that links STORM training to
      actual clinical experience would be the ideal.

PMID- 16796666
TI  - Role discrepancy: is it a common problem among nurses?
AB  - AIM: This paper reports a study of nurses' perceptions of the differences between
      ideal and actual nursing roles, how these perceptions differ according to length
      of experience and the factors that might contribute to these perceived
      differences. BACKGROUND: The literature suggests that nurses tend to experience
      role discrepancy or a mismatch between their ideal and actual roles. Although it
      has been assumed that experienced nurses perceive less role discrepancy than
      inexperienced nurses, either because the former adjust themselves to their actual
      practice or because they have the expertise to improve their practice, this
      assumption has not been tested. METHODS: A survey design was used and the data
      were collected in 2003. Selected items from the Jefferson Survey of Attitudes
      Toward Physician-Nurse Inventory and the Staff Nurse Role Conception Inventory
      were administered to 216 Registered Nurses in Victoria, Australia to measure
      their perceptions of ideal and actual nursing roles. Data were analysed using a t
      test and regression analysis. RESULTS: Nurses with more clinical experience rated
      their ideal and actual nursing roles more positively than those with less
      experience. However, the results showed that both groups of nurses experienced
      the same degree of role discrepancy. Both groups perceived strong role
      discrepancy in the areas of organizational decision-making and provision of
      patient education. Experienced nurses also perceived moderate role discrepancy in
      developing nursing care plans and in the freedom to initiate referrals.
      CONCLUSIONS: Role discrepancy cannot be resolved by having more clinical
      experience. While clinical experience enhances nurses' conceptions of their ideal
      roles, it can also lead to role discrepancy if there are organizational barriers
      that prevent nurses from engaging in their ideal roles. It is important to find a
      way whereby nurses can actualize their ideal views of practice in the current
      healthcare environment.

PMID- 16796668
TI  - Interaction network in cyanobacterial nitrogen regulation: PipX, a protein that
      interacts in a 2-oxoglutarate dependent manner with PII and NtcA.
AB  - Cyanobacteria perceive nitrogen status by sensing intracellular 2-oxoglutarate
      levels. The global nitrogen transcription factor NtcA and the signal transduction
      protein PII are both involved in 2-oxoglutarate sensing. PII proteins, probably
      the most conserved signal transduction proteins in nature, are remarkable for
      their ability to interact with very diverse protein targets in different systems.
      Despite widespread efforts to understand nitrogen signalling in cyanobacteria,
      the involvement of PII in the regulation of transcription activation by NtcA
      remains enigmatic. Here we show that PipX, a protein only present in
      cyanobacteria, interacts with both PII and NtcA and provides a mechanistic link
      between these two factors. A variety of in vivo and in vitro approaches were used
      to study PipX and its interactions with PII and NtcA. 2-Oxoglutarate favours
      complex formation between PipX and NtcA, but impairs binding to PII, suggesting
      that partner swapping between these nitrogen regulators is driven by the 2
      oxoglutarate concentration. PipX is required for NtcA-dependent transcriptional
      activation in vivo, thus implying that PipX may function as a prokaryotic
      transcriptional coactivator.

PMID- 16796669
TI  - Antigenic variation with a twist--the Borrelia story.
AB  - A common mechanism of immune evasion in pathogenic bacteria and protozoa is
      antigenic variation, in which genetic or epigenetic changes result in rapid,
      sequential shifts in a surface-exposed antigen. In this issue of Molecular
      Microbiology, Dai et al. provide the most complete description to date of the
      vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia
      hermsii. This elaborate, plasmid-encoded system involves an expression site that
      can acquire either variable large protein (vlp) or variable small protein (vsp)
      surface lipoprotein genes from 59 different archival copies. The archival vlp and
      vsp genes are arranged in clusters on at least five different plasmids. Gene
      conversion occurs through recombination events at upstream homology sequences
      (UHS) found in each gene copy, and at downstream homology sequences (DHS) found
      periodically among the vlp/vsp archival genes. Previous studies have shown that
      antigenic variation in relapsing fever Borrelia not only permits the evasion of
      host antibody responses, but can also result in changes in neurotropism and other
      pathogenic properties. The vlsE antigenic variation locus of Lyme disease
      spirochaetes, although similar in sequence to the relapsing fever vlp genes, has
      evolved a completely different antigenic variation mechanism involving segmental
      recombination from a contiguous array of vls silent cassettes. These two systems
      thus appear to represent divergence from a common precursor followed by
      functional convergence to create two distinct antigenic variation processes.

PMID- 16796670
TI  - Protease inhibitors in bacteria: an emerging concept for the regulation of
      bacterial protein complexes?
AB  - Serine protease inhibitors (serpins), the antagonists of serine proteases, were
      unknown in the bacterial kingdom until recently. Kang et al. in this issue of
      Molecular Microbiology report the cloning and functional analysis of the three
      serpin genes from the thermophilic anaerobic bacterium Clostridium thermocellum.
      Two of the serpins contain a dockerin module for location in the extracellular
      hydrolytic multienzyme complex, the cellulosome. The susceptibility of
      cellulosome to proteolytic degradation and the presence of a serine protease in
      the same complex provoke speculation that protease inhibitor/protease pairs could
      play hitherto unrecognized roles in protein stability and regulation in bacteria.

PMID- 16796671
TI  - Be in motion . . .
AB  - Most Apicomplexan are obligate intracellular parasites and at different steps of
      their life cycle they invade host cells. The invasive forms are generally called
      zoites and the majority of them largely depend on a unique form of gliding
      motility to invade cells. Although the parasite intracellular motor complex that
      drives gliding motility and/or invasion is shared across different parasite
      stages and species, the extracellular transmembrane adhesins required to
      recognize and bind host molecules are not only species- but also stage-specific
      (even if homologues). This is not such a surprise as different parasite stages
      interact with different hosts or distinct host cells. In this issue, Siden-Kiamos
      et al. shows that specificity extends into the parasite cell, affecting how
      motility is regulated. Why is specificity occurring at this level? And how
      important is it? These are critical issues that will be hopefully addressed in
      the near future.

PMID- 16796672
TI  - Antigenic variation by Borrelia hermsii occurs through recombination between
      extragenic repetitive elements on linear plasmids.
AB  - The relapsing fever agent Borrelia hermsii undergoes multiphasic antigenic
      variation through gene conversion of a unique expression site on a linear plasmid
      by an archived variable antigen gene. To further characterize this mechanism we
      assessed the repertoire and organization of archived variable antigen genes by
      sequencing approximately 85% of plasmids bearing these genes. Most archived genes
      shared with the expressed gene a <or= 62 nucleotide (nt) region, the upstream
      homology sequence (UHS), that surrounded the start codon. The 59 archived
      variable antigen genes were arrayed in clusters with 13 repetitive, 214 nt long
      downstream homology sequence (DHS) elements distributed among them. A fourteenth
      DHS element was downstream of the expression locus. Informative nucleotide
      polymorphisms in UHS regions and DHS elements were applied to the analysis of the
      expression site of relapse serotypes from 60 infected mice in a prospective
      study. For most recombinations, the upstream crossover occurred in the UHS's
      second half, and the downstream crossover was in the DHS's second half. Usually
      the closest archival DHS element was used, but occasionally a more distant DHS
      was employed. The downstream extragenic crossover site in B. hermsii contrasts
      with the upstream [corrected] extragenic crossover site for antigenic variation
      in African trypanosomes.

PMID- 16796673
TI  - The functional repertoire of prokaryote cellulosomes includes the serpin
      superfamily of serine proteinase inhibitors.
AB  - Many of the Firmicutes bacteria responsible for plant polysaccharide degradation
      in Nature produce a multiprotein complex called a cellulosome, which co-ordinates
      glycoside hydrolase assembly, bacterial adhesion to substrate and polysaccharide
      hydrolysis. Cellulosomal proteins possess a dockerin module, which mediates their
      attachment to the scaffoldin protein via its interaction with cohesin modules,
      and only glycoside hydrolases and other carbohydrate active enzymes were known to
      reside within the cellulosome. We show here with Clostridium thermocellum ATCC
      27405 that members of the serpin superfamily of serine proteinase inhibitors,
      which are best recognized for their conformational flexibility and co-ordination
      of key regulatory functions in multicellular eukaryotes, also reside within the
      cellulosome. These studies are the first to expand the cellulosome paradigm of
      protein complex assembly beyond glycoside hydrolase and carbohydrate active
      enzymes, and to include a newly identified functionality in the Firmicutes.

PMID- 16796674
TI  - Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinete
      gliding motility and mosquito midgut invasion.
AB  - Apicomplexan parasites critically depend on a unique form of gliding motility to
      colonize their hosts and to invade cells. Gliding requires different stage and
      species-specific transmembrane adhesins, which interact with an intracellular
      motor complex shared across parasite stages and species. How gliding is regulated
      by extracellular factors and intracellular signalling mechanisms is largely
      unknown, but current evidence suggests an important role for cytosolic calcium as
      a second messenger. Studying a Plasmodium berghei gene deletion mutant, we here
      provide evidence that a calcium-dependent protein kinase, CDPK3, has an important
      function in regulating motility of the ookinete in the mosquito midgut. We show
      that a cdpk3- parasite clone produces morphologically normal ookinetes, which
      fail to engage the midgut epithelium, due to a marked reduction in their ability
      to glide productively, resulting in marked reduction in malaria transmission to
      the mosquito. The mutant was successfully complemented with an episomally
      maintained cdpk3 gene, restoring mosquito transmission to wild-type level. cdpk3-
      ookinetes maintain their full genetic differentiation potential when
      microinjected into the mosquito haemocoel and cdpk3- sporozoites produced in this
      way are motile and infectious, suggesting an ookinete-limited essential function
      for CDPK3.

PMID- 16796675
TI  - A new FtsZ-interacting protein, YlmF, complements the activity of FtsA during
      progression of cell division in Bacillus subtilis.
AB  - The assembly of ring-like structures, composed of FtsZ proteins (i.e. the Z
      ring), is the earliest and most essential process in bacterial cytokinesis. It
      has been shown that this process is directly regulated by the FtsZ-binding
      proteins, FtsA, ZapA, and EzrA, in Bacillus subtilis. In this study, protein
      complexes that are involved in Z-ring formation were chemically cross-linked in
      vivo, purified by affinity chromatography, and analysed by mass spectrometry.
      Analysis of the results identified YlmF as a new component of the FtsZ complex.
      Yeast two-hybrid analysis and fluorescence microscopy of YFP-YlmF in B. subtilis
      cells indicated YlmF localizes to the division site in an FtsZ-dependent manner.
      A single disruption of YlmF resulted in a slight elongation of cells; however,
      simultaneous inactivation of both YlmF and FtsA showed synthetic lethality caused
      by complete blockage of cell division due to the defect in Z-ring formation. In
      contrast, the ftsA-null mutant phenotype, caused by inefficient Z-ring formation,
      could be complemented by overexpression of YlmF. These results suggest that YlmF
      has an overlapping function with FtsA in stimulating the formation of Z rings in
      B. subtilis.

PMID- 16796676
TI  - Integration Host Factor is required for FarR repression of the farAB-encoded
      efflux pump of Neisseria gonorrhoeae.
AB  - The farAB operon encodes an efflux pump system that mediates the resistance of
      Neisseria gonorrhoeae to antimicrobial long-chain fatty acids. We previously
      observed that expression of farAB is negatively regulated by the FarR repressor.
      In this study, we examined the molecular mechanism by which FarR represses
      expression of farAB. DNase I footprinting analysis, coupled with a deletion
      analysis of the farAB promoter region, indicated that FarR binds to three sites
      (termed sites A, B and C) within the DNA sequence upstream of farA; genetic
      analysis revealed, however, that site B is not required for FarR repression of
      farAB. This repression also required the presence of Integration Host Factor
      (IHF), which was found to bind to sequences located between FarR binding sites A
      and C. We determined that IHF binding to the farAB promoter region could inhibit
      transcription in vitro and that such binding induced a bending of the target DNA,
      which we propose to be important in regulating this operon. IHF binding to the
      promoter region was found to stabilize the binding of FarR to its binding sites A
      and C and as a consequence, enhanced repression of farAB expression mediated by
      FarR. We propose a model in which expression of the farAB-encoded efflux pump in
      N. gonorrhoeae is modulated by the DNA binding activities of FarR and IHF.

PMID- 16796677
TI  - Assembly and role of pili in group B streptococci.
AB  - Streptococcus agalactiae[group B streptococcus (GBS)] is the leading cause of
      neonatal pneumonia, sepsis and meningitis. An in silico genome analysis indicated
      that GBS strain NEM316 encodes five putative sortases, including the major class
      A sortase enzyme and four class C sortases. The genes encoding the class C
      sortases are tandemly arranged in two different loci, srtC1-C2 and srtC3-C4, with
      a similar genetic organization and are thought to be involved in pilus
      biosynthesis. Each pair of sortase genes is flanked by LPXTG protein encoding
      genes, two upstream and one downstream, and a divergently transcribed regulatory
      gene located upstream from this locus. We demonstrated that strain NEM316
      expresses only the srtC3-C4 locus, which encodes three surface proteins (Gbs1474,
      Gbs1477 and Gbs1478) that polymerize to form appendages resembling pili.
      Structural and functional analysis of this locus revealed that: (i) the
      transcriptional activator RogB is required for expression of the srtC3-C4 operon;
      (ii) Gbs1477, and either SrtC3 or SrtC4 are absolutely required for pilus
      biogenesis; and (iii) GBS NEM316 pili are composed of three surface proteins,
      Gbs1477, the bona fide pilin which is the major component, Gbs1474, a minor
      associated component, and Gbs1478, a pilus-associated adhesin. Surprisingly,
      pilus-like structures can be formed in the absence of the two minor components,
      i.e. the putative anchor Gbs1474 or the adhesin Gbs1478. Adherence assays showed
      that Gbs1478 confers adhesive capacity to the pilus. This study provides the
      first evidence that adhesive pili are also present in Gram-positive pathogens.

PMID- 16796678
TI  - Two Ser/Thr protein kinases essential for efficient aggregation and spore
      morphogenesis in Myxococcus xanthus.
AB  - Myxococcus xanthus has a complex life cycle that involves vegetative growth and
      development. Previously, we described the espAB locus that is involved in timing
      events during the initial stages of fruiting body formation. Deletion of espA
      caused early aggregation and sporulation, whereas deletion of espB caused delayed
      aggregation and sporulation resulting in reduced spore yields. In this study, we
      describe two genes, pktA5 and pktB8, that flank the espAB locus and encode
      Ser/Thr protein kinase (STPK) homologues. Cells deficient in pktA5 or pktB8
      formed translucent mounds and produced low spore yields, similar in many respects
      to espB mutants. Double mutant analysis revealed that espA was epistatic to pktA5
      and pktB8 with respect to aggregation and fruiting body morphology, but that
      pktA5 and pktB8 were epistatic to espA with respect to sporulation efficiency.
      Expression profiles of pktA5-lacZ and pktB8-lacZ fusions and Western blot
      analysis showed that the STPKs are expressed under vegetative and developmental
      conditions. In vitro kinase assays demonstrated that the RD kinase, PktA5,
      autophosphorylated on threonine residue(s) and phosphorylated the artificial
      substrate, myelin basic protein. In contrast, autophosphorylation of the non-RD
      kinase, PktB8, was not observed in vitro; however, the phenotype of a pktB8
      kinase-dead point mutant resembled the pktB8 deletion mutant, indicating that
      this residue was important for function and that it likely functions as a kinase
      in vivo. Immunoprecipitation of Tap-tagged PktA5 and PktB8 revealed an
      interaction with EspA during development in M. xanthus. These results, taken
      together, suggest that PktA5 and PktB8 are STPKs that function during development
      by interacting with EspA and EspB to regulate M. xanthus development.

PMID- 16796679
TI  - Bacillus subtilis Fnr senses oxygen via a [4Fe-4S] cluster coordinated by three
      cysteine residues without change in the oligomeric state.
AB  - The oxygen regulator Fnr is part of the regulatory cascade in Bacillus subtilis
      for the adaptation to anaerobic growth conditions. In vivo complementation
      experiments revealed the essential role of only three cysteine residues (C227,
      C230, C235) at the C-terminus of B. subtilis Fnr for the transcriptional
      activation of the nitrate reductase operon (narGHJI) and nitrite extrusion
      protein gene (narK) promoters. UV/VIS, electron paramagnetic spin resonance (EPR)
      and Mossbauer spectroscopy experiments in combination with iron and sulphide
      content determinations using anaerobically purified recombinant B. subtilis Fnr
      identified the role of these three cysteine residues in the formation of one [4Fe
      4S]2+ cluster per Fnr molecule. The obtained Mossbauer parameters are supportive
      for a [4Fe-4S]2+ cluster with three cysteine ligated iron sites and one non
      cysteine ligated iron site. Gel filtration experiments revealed a stable dimeric
      structure for B. subtilis Fnr which is independent of the presence of the [4Fe
      4S]2+ cluster. Gel mobility shift and in vitro transcription assays demonstrated
      the essential role of an intact [4Fe-4S]2+ cluster for promoter binding and
      transcriptional activation. An amino acid exchange introduced in the proposed
      alphaD-helix of B. subtilis Fnr (G149S) abolished its in vivo and in vitro
      activities indicating its importance for intramolecular signal transduction. The
      clear differences in the localization and coordination of the [4Fe-4S] cluster
      and in the organization of the oligomeric state between Escherichia coli and B.
      subtilis Fnr indicate differences in their mode of action.

PMID- 16796680
TI  - Autoinducer 2: a concentration-dependent signal for mutualistic bacterial biofilm
      growth.
AB  - 4,5-Dihydroxy-2,3-pentanedione (DPD), a product of the LuxS enzyme in the
      catabolism of S-ribosylhomocysteine, spontaneously cyclizes to form autoinducer 2
      (AI-2). AI-2 is proposed to be a universal signal molecule mediating interspecies
      communication among bacteria. We show that mutualistic and abundant biofilm
      growth in flowing saliva of two human oral commensal bacteria, Actinomyces
      naeslundii T14V and Streptococcus oralis 34, is dependent upon production of AI-2
      by S. oralis 34. A luxS mutant of S. oralis 34 was constructed which did not
      produce AI-2. Unlike wild-type dual-species biofilms, A. naeslundii T14V and an
      S. oralis 34 luxS mutant did not exhibit mutualism and generated only sparse
      biofilms which contained a 10-fold lower biomass of each species. Restoration of
      AI-2 levels by genetic or chemical (synthetic AI-2 in the form of DPD)
      complementation re-established the mutualistic growth and high biomass
      characteristic for the wild-type dual-species biofilm. Furthermore, an optimal
      concentration of DPD was determined, above and below which biofilm formation was
      suppressed. The optimal concentration was 100-fold lower than the detection limit
      of the currently accepted AI-2 assay. Thus, AI-2 acts as an interspecies signal
      and its concentration is critical for mutualism between two species of oral
      bacteria grown under conditions that are representative of the human oral cavity.

PMID- 16796681
TI  - Leishmania histone H1 overexpression delays parasite cell-cycle progression,
      parasite differentiation and reduces Leishmania infectivity in vivo.
AB  - Episomal expression of Leishmania histone H1 sense mRNAs in Leishmania major
      promastigotes was found previously to result in overexpression of this molecule
      and to reduce parasite infectivity in vitro. Herein, we evaluated the in vivo
      infectivity of these transfectants, in BALB/c mice, and showed that it is
      dramatically reduced. No lesions were observed in this group of mice and this was
      associated with an extremely low number of parasites both in the footpad and in
      the draining lymph nodes. Interestingly, the transfectants-reduced infectivity
      was associated with a delay in their cell-cycle progression and differentiation
      to axenic amastigotes, assessed in vitro. Therefore, the dramatic reduction in
      their infectivity may be attributed to the above-mentioned phenotypic
      modifications. As the metazoan linker histone H1(0) homologue is known to delay
      cell-cycle progression in mammalian cells we investigated whether its Leishmania
      counterpart, which possesses homology to its C-terminal region, when expressed in
      mammalian cells may also affect their cell-cycle progression. It was thus shown
      that Leishmania histone H1 expressed in COS7 and NIH 3T3 cells, delays cell-cycle
      progression in these cells too. The latter strengthens the phenotype observed in
      Leishmania and provides evidence that critical functions of histone H1 molecules
      are conserved throughout evolution.

PMID- 16796682
TI  - Cooperation of two distinct ExpR regulators controls quorum sensing specificity
      and virulence in the plant pathogen Erwinia carotovora.
AB  - Quorum sensing, the population density-dependent regulation mediated by N
      acylhomoserine lactones (AHSL), is essential for the control of virulence in the
      plant pathogen Erwinia carotovora ssp. carotovora (Ecc). In Erwinia carotovora
      ssp. the AHSL signal with an acyl chain of either 6 or 8 carbons is generated by
      an AHSL synthase, the expI gene product. This work demonstrates that the AHSL
      receptor, ExpR1, of Ecc strain SCC3193 has strict specificity for the cognate
      AHSL 3-oxo-C8-HSL. We have also identified a second AHSL receptor (ExpR2) and
      demonstrate a novel quorum sensing mechanism, where ExpR2 acts synergistically
      with the previously described ExpR1 to repress virulence gene expression in Ecc.
      We show that this repression is released by addition of AHSLs and appears to be
      largely mediated via the negative regulator RsmA. Additionally we show that ExpR2
      has the novel property to sense AHSLs with different acyl chain lengths. The expI
      expR1 double mutant is able to act in response to a number of different AHSLs,
      while the expI expR2 double mutant can only respond to the cognate signal of Ecc
      strain SCC3193. These results suggest that Ecc is able to react both to the
      cognate AHSL signal and the signals produced by other bacterial species.

PMID- 16796683
TI  - Proteolysis of the replication checkpoint protein Sda is necessary for the
      efficient initiation of sporulation after transient replication stress in
      Bacillus subtilis.
AB  - Cells of Bacillus subtilis actively co-ordinate the initiation of sporulation
      with DNA replication and repair. Conditions that perturb replication initiation
      or replication elongation induce expression of a small protein, Sda, that
      specifically inhibits the histidine kinases required to initiate spore
      development. Previously, the role of Sda has been studied during chronic blocks
      to DNA replication. Here we show that induction of Sda is required to delay the
      initiation of sporulation when replication elongation is transiently blocked or
      after UV irradiation. During the recovery phase, cells efficiently sporulated,
      but this required the proteolysis of Sda. The rapid proteolysis of Sda required
      the ClpXP protease and the uncharged C-terminal sequence of Sda. Replacing the
      last two residues of Sda, both serines, with aspartic acids markedly stabilized
      Sda. Strains expressing sdaDD from the endogenous sda locus were unable to
      efficiently initiate sporulation after transient replication stress. We conclude
      that the Sda replication checkpoint is required to delay the initiation of
      sporulation when DNA replication is transiently perturbed, and that the intrinsic
      instability of Sda contributes to shutting off the pathway. The Sda checkpoint
      thus co-ordinates early events of spore development, including the polar cell
      division, with successful completion of chromosome replication.

PMID- 16796684
TI  - Mycoplasma genitalium mg200 and mg386 genes are involved in gliding motility but
      not in cytadherence.
AB  - Isolation and characterization of transposon-generated Mycoplasma genitalium
      gliding-deficient mutants has implicated mg200 and mg386 genes in gliding
      motility. The proposed role of these genes was confirmed by restoration of the
      gliding phenotype in deficient mutants through gene complementation with their
      respective mg386 or mg200 wild-type copies. mg200 and mg386 are the first
      reported gliding-associated mycoplasma genes not directly involved in
      cytadherence. Orthologues of MG200 and MG386 proteins are also found in the slow
      gliding mycoplasmas, Mycoplasma pneumoniae and Mycoplasma gallisepticum,
      suggesting the existence of a unique set of proteins involved in slow gliding
      motility. MG200 and MG386 proteins share common features, such as the presence of
      enriched in aromatic and glycine residues boxes and an acidic and proline-rich
      domain, suggesting that these motifs could play a significant role in gliding
      motility.

PMID- 16796685
TI  - (p)ppGpp regulates type 1 fimbriation of Escherichia coli by modulating the
      expression of the site-specific recombinase FimB.
AB  - In this report we have examined the role of the regulatory alarmone (p)ppGpp on
      expression of virulence determinants of uropathogenic Escherichia coli strains.
      The ability to form biofilms is shown to be markedly diminished in (p)ppGpp
      deficient strains. We present evidence (i) that (p)ppGpp tightly regulates
      expression of the type 1 fimbriae in both commensal and pathogenic E. coli
      isolates by increasing the subpopulation of cells that express the type 1
      fimbriae; and (ii) that the effect of (p)ppGpp on the number of fimbrial
      expressing cells can ultimately be traced to its role in transcription of the
      fimB recombinase gene, whose product mediates inversion of the fim promoter to
      the productive (ON) orientation. Primer extension analysis suggests that the
      effect of (p)ppGpp on transcription of fimB occurs by altering the activity of
      only one of the two fimB promoters. Furthermore, spontaneous mutants with
      properties characteristic of ppGpp(0) suppressors restore fimB transcription and
      consequent downstream effects in the absence of (p)ppGpp. Consistently, the
      rpoB3770 allele also fully restores transcription of fimB in a ppGpp(0) strain
      and artificially elevated levels of FimB bypass the need for (p)ppGpp for type 1
      fimbriation. Our findings suggest that the (p)ppGpp-stimulated expression of type
      1 fimbriae may be relevant during the interaction of pathogenic E. coli with the
      host.

PMID- 16796686
TI  - Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of
      Protochlamydia amoebophila.
AB  - Protochlamydia amoebophila UWE25 is related to the Chlamydiaceae comprising major
      pathogens of humans, but thrives as obligate intracellular symbiont in the
      protozoan host Acanthamoeba sp. The genome of P. amoebophila encodes five
      paralogous carrier proteins belonging to the nucleotide transporter (NTT) family.
      Here we report on three P. amoebophila NTT isoforms, PamNTT2, PamNTT3 and
      PamNTT5, which possess several conserved amino acid residues known to be critical
      for nucleotide transport. We demonstrated that these carrier proteins are able to
      transport nucleotides, although substrate specificities and mode of transport
      differ in an unexpected manner and are unique among known NTTs. PamNTT2 is a
      counter exchange transporter exhibiting submillimolar apparent affinities for all
      four RNA nucleotides, PamNTT3 catalyses an unidirectional proton-coupled
      transport confined to UTP, whereas PamNTT5 mediates a proton-energized GTP and
      ATP import. All NTT genes of P. amoebophila are transcribed during intracellular
      multiplication in acanthamoebae. The biochemical characterization of all five NTT
      proteins from P. amoebophila in this and previous studies uncovered that these
      metabolically impaired bacteria are intimately connected with their host cell's
      metabolism in a surprisingly complex manner.

PMID- 16796687
TI  - PDR16-mediated azole resistance in Candida albicans.
AB  - Many Candida albicans azole-resistant (AR) clinical isolates overexpress the CDR1
      and CDR2 genes encoding homologous multidrug transporters of the ATP-binding
      cassette family. We show here that these strains also overexpress the PDR16 gene,
      the orthologue of Saccharomyces cerevisiae PDR16 encoding a phosphatidylinositol
      transfer protein of the Sec14p family. It has been reported that S. cerevisiae
      pdr16Delta mutants are hypersusceptible to azoles, suggesting that C. albicans
      PDR16 may contribute to azole resistance in these isolates. To address this
      question, we deleted both alleles of PDR16 in an AR clinical strain
      overexpressing the three genes, using the mycophenolic acid resistance flipper
      strategy. Our results show that the homozygous pdr16Delta/pdr16Delta mutant is
      approximately twofold less resistant to azoles than the parental strain whereas
      reintroducing a copy of PDR16 in the mutant restored azole resistance,
      demonstrating that this gene contributes to the AR phenotype of the cells. In
      addition, overexpression of PDR16 in azole-susceptible (AS) C. albicans and S.
      cerevisiae strains increased azole resistance by about twofold, indicating that
      an increased dosage of Pdr16p can confer low levels of azole resistance in the
      absence of additional molecular alterations. Taken together, these results
      demonstrate that PDR16 plays a role in C. albicans azole resistance.

PMID- 16796688
TI  - Identification of a response regulator gene for catabolite control from a PCB
      degrading beta-proteobacteria, Acidovorax sp. KKS102.
AB  - Acidovorax sp. (formally Pseudomonas sp.) strain KKS102 carries a bph operon for
      the degradation of PCB/biphenyl. Transcription from the pE promoter for the bph
      operon was found to be under catabolite control, i.e. the promoter activity was
      at a lower level when succinate, fumarate or acetate was added to the culture.
      Some mutations in the immediate upstream region of the pE promoter resulted in
      catabolite-insensitive and constitutively low promoter activity, suggesting that
      a transcriptional activator was involved in catabolite control. A genetic screen
      for a pE promoter activator identified two tandemly arranged genes, bphP and
      bphQ, that encoded proteins homologous to the sensor kinases and response
      regulators, respectively, of two-component regulatory system. In the bphPQ double
      mutant, pE promoter activity was weak and catabolite-insensitive, and a supply of
      the bphQ gene alone led to the restoration of the catabolite response. The
      mechanism of catabolite repression in KKS102 is explained in terms of inhibition
      of activation by BphQ. The genes highly similar to bphQ were found from several
      beta-proteobacteria, such as Burkholderia cenocepacia J2315, B. multivorans
      ATCC17616, B. xenovorans LB400 and Ralstonia solanacearum RS1085.

PMID- 16796689
TI  - Regulation of Escherichia coli hchA, a stress-inducible gene encoding molecular
      chaperone Hsp31.
AB  - Escherichia coli Hsp31 is a homodimeric member of the ThiI/DJ-1/PfpI superfamily
      that combines molecular chaperone and aminopeptidase activities. Although it was
      originally identified on the basis of its induction by heat shock, little is
      known about the regulation of hchA, the structural gene encoding Hsp31. Here, we
      show that hchA is transcribed from dual promoters recognized by the sigmaD
      (sigma70) and sigmaS (sigma38) subunits of RNA polymerase (E). In exponentially
      growing cells, the nucleoid-binding protein H-NS downregulates Hsp31 synthesis,
      and hchA thermal induction primarily relies on the relief of H-NS-mediated
      silencing of EsigmaD-dependent transcription. This uncommon alternative to the
      use of a heat-shock sigma factor guarantees that Hsp31 concentration remains high
      throughout the length of the high temperature exposure phase. Entry into
      stationary phase leads to enhanced hchA transcription from its EsigmaS-dependent
      promoter. Consistent with a role of Hsp31 in the management of starvation, hchA
      null mutants exhibit a decrease ability to survive in deep stationary phase
      relative to hchA+ cells. Based on hchA heat-inducibility and membership in the
      sigmaS general stress regulon, we propose that Hsp31 performs a protective
      function under a wide range of stress conditions.

PMID- 16796690
TI  - A mechanical role for the chemotaxis system in swarming motility.
AB  - The chemotaxis system, but not chemotaxis, is essential for swarming motility in
      Salmonella enterica serovar Typhimurium. Mutants in the chemotaxis pathway
      exhibit fewer and shorter flagella, downregulate class 3 or 'late' motility
      genes, and appear to be less hydrated when propagated on a surface. We show here
      that the output of the chemotaxis system, CheY approximately P, modulates motor
      bias during swarming as it does during chemotaxis, but for a distinctly different
      end. A constitutively active form of CheY was found to promote swarming in the
      absence of several upstream chemotaxis components. Two point mutations that
      suppressed the swarming defect of a cheY null mutation mapped to FliM, a protein
      in the motor switch complex with which CheY approximately P interacts. A common
      property of these suppressors was their increased frequency of motor reversal.
      These and other data suggest that the ability to switch motor direction is
      important for promoting optimal surface wetness. If the surface is sufficiently
      wet, exclusively clockwise or counterclockwise directions of motor rotation will
      support swarming, suggesting also that the bacteria can move on a surface with
      flagellar bundles of either handedness.

PMID- 16796692
TI  - Importance of gastrointestinal ingestion and macromolecular antigens in the vein
      for oral tolerance induction.
AB  - Oral administration of a certain dose of antigen can generally induce
      immunological tolerance against the same antigen. In this study, we showed the
      temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral
      blood of mice after the oral administration of OVA. Furthermore, we detected
      45,000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based
      on this observation, we examined whether the injection of intact OVA into the
      portal or peripheral vein induces immunological tolerance against OVA. We found
      that the intravenous injection of intact OVA did not induce immunological
      tolerance but rather enhanced OVA-specific antibody production in some
      subclasses, suggesting that OVA antigens via the gastrointestinal tract but not
      intact OVA may contribute to establish immunological tolerance against OVA.
      Therefore, we examined the effects of digesting intact OVA in the
      gastrointestinal tract on the induction of oral tolerance. When mice were orally
      administered or injected into various gastrointestinal organs, such as the
      stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA-specific
      antibody production and delayed-type hypersensitivity (DTH) response were
      significantly enhanced in mice injected into the ileum or colon, compared with
      orally administered mice. These results suggest that although macromolecular OVA
      antigens are detected after oral administration of OVA in tolerant-mouse serum,
      injection of intact OVA cannot contribute to tolerance induction. Therefore, some
      modification of macromolecular OVA in the gastrointestinal tract and ingestion
      may be essential for oral tolerance induction.

PMID- 16796693
TI  - Abortive activation precedes functional deletion of CD8+ T cells following
      encounter with self-antigens expressed by resting B cells in vivo.
AB  - InsHA mice express the haemagglutinin (HA) protein from influenza virus A/PR/8
      H1N1 (PR8) as a self antigen on pancreatic islet beta cells. We have utilized
      these mice to investigate the ability of resting B cells expressing Kd to induce
      self-tolerance among naive KdHA-specific clone 4 CD8+ T cells. Adoptive transfer
      of KdHA-peptide-pulsed resting B cells into clone 4-->InsHA recipients resulted
      in the activation and proliferation of clone 4 CD8+ T cells throughout the
      peripheral lymphoid tissues. Significantly, proliferation was not associated with
      the acquisition of T cell effector function; as evidenced by a lack of interferon
      gamma production and the complete absence of any autoimmune pathology even after
      immunization of recipient mice with PR8. These data demonstrate that resting B
      cells pulsed with self-epitopes can induce abortive activation of potentially
      self-reactive naive CD8+ T cells resulting in their functional deletion from the
      peripheral T-cell repertoire in the absence of any associated autoimmunity.

PMID- 16796694
TI  - A phase II trial of imatinib mesylate in patients with biochemical relapse of
      prostate cancer after definitive local therapy.
AB  - OBJECTIVE: To determine the biological effects of imatinib mesylate (STI-571,
      Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by
      prostate-specific antigen (PSA) kinetics in men with biochemical relapse of
      prostate cancer after definitive local therapy. PATIENTS AND METHODS: Men with
      prostate cancer, who had had definitive local therapy, with nonmetastatic
      recurrent disease as manifested by a rising PSA level, were enrolled on this
      phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and
      continuously until disease progression or unacceptable toxicity. The PSA level
      was measured monthly. RESULTS: In all, 20 men with biochemically relapsed
      prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of
      the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had
      decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time
      (PSADT) could be calculated (those with increasing PSA level) the median PSADT
      did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men
      discontinued therapy due to toxicity and the trial was stopped early due to
      toxicity. CONCLUSIONS: Based on the lack of PSA modulation and pronounced
      toxicities leading to early closure of this trial, further study of single-agent
      imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this
      patient population.

PMID- 16796695
TI  - Trends in the operative management of renal tumors over a 14-year period.
AB  - OBJECTIVE: To review the trends in the operative management of renal tumours over
      a 14-year period at a university hospital, as the therapeutic options available
      for treating renal tumours have increased over the past decade. PATIENTS AND
      METHODS: The study was a retrospective chart review of 1621 consecutive patients
      undergoing treatment for renal tumours from January 1991 to March 2005. The
      characteristics assessed included patient demographics, tumour size, operative
      duration and treatment. RESULTS: During the study period, 624 (38.6%) open, 883
      (54.6%) laparoscopic and 111 (6.7%) percutaneous approaches were performed. The
      number of renal tumours treated increased annually, as did the use of minimally
      invasive techniques (93.4% in 2005). Conversely, the number of open surgical
      treatments used declined both absolutely and proportionally. Over the study
      period, for tumours of <or=4 cm, laparoscopic partial nephrectomy was the most
      common approach (41.0%). Percutaneous ablation has also made an impact as a
      treatment method for small tumours (13.8% in 2005). For tumours of >7 cm, open
      radical nephrectomy (ORN) was the most common method of treatment over all years.
      However, since 2002, laparoscopic radical nephrectomy (LRN) surgery has been
      increasingly used over ORN for treating this tumour group (73% LRN vs 19.2% ORN
      in 2004). CONCLUSION: The available treatment options for renal tumours have
      increased significantly since the early 1990s. At a university hospital in which
      there are physicians with a specific interest in minimally invasive surgery and
      ablative treatments, minimally invasive approaches have become the standard
      treatment.

PMID- 16796696
TI  - The effect of intracavernosal growth differentiation factor-5 therapy in a rat
      model of cavernosal nerve injury.
AB  - OBJECTIVE: To determine whether the intracavernosal application of growth
      differentiation factor-5 (GDF-5) influences nerve regeneration and erectile
      function after cavernosal nerve injury in a rat model. MATERIALS AND METHODS:
      Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups:
      eight had a sham operation (uninjured controls), while 24 had bilateral
      cavernosal nerve crush. The crush-injury groups were treated at the time of
      injury with an impregnated collagen sponge implanted into the right corpus
      cavernosum. The sponge contained no GDF-5 (injured controls), 2 microg (low
      concentration), or 20 microg GDF-5 (high concentration). Erectile function was
      assessed by cavernosal nerve electrostimulation at 8 weeks. Midshaft penile
      tissue samples were histochemically evaluated for neuronal nitric oxide synthase
      (nNOS)-containing fibres in the dorsal penile nerve. RESULTS: There was no
      erectile dysfunction in the uninjured control group, as shown by a mean (sem)
      maximal increase in intracavernosal pressure (ICP) of 149.5 (17.0) cmH(2)O on
      stimulation. By comparison, the ICP decreased in the injured control group, by
      21.3 (6.7) cmH(2)O. After cavernosal nerve injury, the recovery of erectile
      function was greatest in the low-concentration GDF-5 group; the maximum ICP
      increase was 40.8 (13.3) cmH(2)O, vs 24.3 (5.9) cmH(2)O for 20 microg GDF-5.
      Histologically, the low-concentration group had significantly more nNOS
      containing nerve fibres, at 163 (24.7), than the high-concentration group, at 76
      (17.3), or injured controls, at 67 (23.8). By contrast, the uninjured controls
      had a mean of 538 (40.6) nerve fibres in the dorsal nerve. CONCLUSION: Bilateral
      cavernosal nerve crush resulted in erectile dysfunction with accompanying
      neurological changes in the rat. The intracavernosal application of GDF-5
      enhanced the recovery of erectile function and n-NOS nerve preservation, with a 2
      microg dose giving the most promising results.

PMID- 16796697
TI  - Radical cystectomy with ileal conduit diversion: early prospective evaluation of
      the impact of robotic assistance.
AB  - OBJECTIVE: To compare the performance of radical cystectomy with ileal conduit
      diversion by standard methods with that using the assistance of the daVinci
      robotic system (Intuitive Surgical, Sunnyvale, CA, USA). PATIENTS AND METHODS:
      From November 2003 to August 2005, we performed 30 radical cystectomies with
      ileal conduit urinary diversions on patients with bladder cancer. Seven patients
      (one woman) had a cystectomy with the daVinci system and 23 (nine women) had a
      standard cystectomy. Data were collected prospectively, including estimated blood
      loss (EBL), transfusion requirement, operative duration, hospital stay and body
      mass index (BMI), and compared. RESULTS: The mean EBL and transfusion
      requirements for standard and daVinci-assisted cases was 1109 and 479 mL (P =
      0.002) and 2.7 and 1.6 units (P = 0.14), respectively. Four of seven patients
      received a transfusion in the robotic group, and 20 of 23 in the standard group
      (P = 0.084). The mean operative duration was 638 and 507 min (P = 0.005) for the
      daVinci and standard group, respectively, with respective mean hospital stays of
      11 and 13 days (P = 0.52). There was no difference in patient BMI between the
      groups (P = 0.22). CONCLUSION: The daVinci-assisted cystectomy appears to offer
      some advantages over standard cystectomy. Larger randomized studies are needed to
      confirm these findings.

PMID- 16796698
TI  - Validation of a nomogram predicting the probability of lymph node invasion based
      on the extent of pelvic lymphadenectomy in patients with clinically localized
      prostate cancer.
AB  - OBJECTIVE: To develop a multivariate nomogram to predict the rate of lymph node
      invasion (LNI) in patients with clinically localized prostate cancer according to
      the extent of extended pelvic lymphadenectomy (PLND), which is associated with
      significantly higher rate of LNI. PATIENTS AND METHODS: The study comprised 781
      consecutive patients (median age 66.6 years, range 45-85) treated with PLND and
      radical retropubic prostatectomy (RRP) for clinically localized prostate cancer.
      Their median (range) prostate-specific antigen (PSA) level was 7 (1.03-49.91)
      ng/mL, and their clinical stages were T1c in 433 (55.4%), T2 in 328 (42%) and T3
      in 20 (2.6%). Biopsy Gleason sums were <or= 6 in 514 (65.8%), 7 in 204 (26.1%)
      and 8-10 in 63 (8.1%). Multivariate logistic regression models were used to test
      the association between predictors including PSA level, biopsy Gleason sum,
      clinical stage, number of nodes removed and the rate of LNI. Finally, regression
      coefficients were used to develop a nomogram, which was internally validated with
      200 bootstrap re-samples. RESULTS: The median (range) number of lymph nodes
      removed was 14 (2-40); LNI was detected in 71 patients (9.1%). The univariate
      predictive accuracy for total PSA level, clinical stage, biopsy Gleason sum and
      number of total nodes removed and examined was 64.2%, 59.8%, 74% and 62.9%,
      respectively. Except for PSA (P = 0.2), all variables were statistically
      significant multivariate predictors of LNI at RRP (P <or= 0.001). A nomogram
      based on clinical stage, PSA level, biopsy Gleason sum and the number of total
      lymph nodes removed was 78.6% accurate, and 1.8% more accurate than a nomogram
      without the number of removed lymph nodes. CONCLUSIONS: The extent of PLND is
      directly related to the probability of LNI. The risk of LNI increases linearly,
      and is proportional to the number of nodes removed and examined. The effect of
      the increased probability of LNI is weighted more heavily in men with more
      advanced clinical stage and grade.

PMID- 16796699
TI  - Vascular resistance in the prostate evaluated by colour Doppler ultrasonography:
      is benign prostatic hyperplasia a vascular disease?
AB  - OBJECTIVE: To evaluate prostatic vascular resistance by measuring the resistive
      index (RI), and flow velocity using colour Doppler ultrasonography (CDUS), in
      normal prostates and in patients with benign prostatic hyperplasia (BPH) or
      prostate cancer, as BPH is considered to be a result of urogenital ageing and
      studies suggest that hyperplasia in the stromal and glandular compartments might
      be induced by stromal growth secondary to hypoxia, which in turn results from
      abnormal blood flow patterns. PATIENTS, SUBJECTS AND METHODS: Ninety-two men (22
      with normal prostates, 45 with BPH and 25 with prostate cancer; mean age 56
      years) were prospectively evaluated by CDUS. The RI values for the peripheral,
      central and transition zones were assessed by one investigator. The diagnosis of
      BPH and prostate cancer was established from histological findings. RESULTS: The
      mean (sd) RI in the transition zone was significantly higher only in patients
      with BPH, at 0.77 (0.05), vs 0.65 (0.05) in the other two groups. In the
      peripheral and central zones there was no significant difference in the RI among
      the three groups. Arterial CDUS flow velocity was increased in the transition
      zone of patients with BPH, but not in the peripheral and central zones.
      CONCLUSIONS: The present results support the hypothesis that an age-related
      impairment of blood supply to the lower urinary tract might have a role in the
      development of BPH. Although prostate cancer cannot be excluded by measuring RI,
      high RI values (>0.75) in the transition zone are indicative of BPH.

PMID- 16796700
TI  - The impact of new insights and revised practice guidelines on prescribing drugs
      in the treatment of Type 2 diabetes mellitus.
AB  - AIMS: The aim of this study was to investigate the impact of new insights and
      revised guidelines on initial and follow-up treatment with antihyperglycaemic
      drugs over the period 1998-2003. METHODS: The InterAction Database (IADB), which
      contains pharmacy dispensing data from 53 community pharmacies in the Northern
      and Eastern part of the Netherlands, was used in this study. Prevalence and
      incidence rates of oral antihyperglycaemic drug use were calculated for each
      year. Follow-up treatment was compared for two cohorts of initial users of oral
      antihyperglycaemic drugs, starting treatment either 1 year before or 1 year after
      guideline revision. RESULTS: The prevalence and incidence rate of oral
      antihyperglycaemic drug use increased over the study period from 1.8% to 2.4% (P
      < 0.001) and 0.3% to 0.4% (P = 0.04). The proportion of metformin as initial
      treatment increased rapidly in the observation period from 14% to 50% (P <
      0.001). Initial users of metformin in 2000 received additional treatment with a
      sulphonylurea in the follow-up period less often compared with those who started
      metformin in 1998 (46%vs. 60%, P < 0.004). In contrast, initial users of
      sulphonylurea in 2000 received additional treatment with metformin more often
      compared with those who started a sulphonylurea in 1998 (42%vs. 36%, P < 0.008).
      The new drugs, thiazolidinediones and meglitinides, were seldom used as initial
      treatment. CONCLUSIONS: New insights and the revision of the practice guideline
      were followed by a significant increase in both initial and follow-up treatment
      with metformin among patients with Type 2 diabetes mellitus.

PMID- 16796701
TI  - Homoeopathic and herbal prescribing in general practice in Scotland.
AB  - AIMS: To investigate the current levels of homoeopathic and herbal prescribing in
      Scottish general practice. METHODS: Prescribing of homoeopathic and herbal
      remedies in primary care was assessed in 1891 669 patients for the year 2003
      2004, using computerized prescribing data retrieved from 323 general practices in
      Scotland. RESULTS: Forty-nine percent of practices prescribed homoeopathic and
      32% herbal remedies. A total of 193 homoeopathic and 17 herbal remedies were
      prescribed, with 5% of practices accounting for 46% of patients and 50% of
      remedies. Four thousand one hundred and sixty patients (2.2/1000 registered
      patients) were prescribed at least one homoeopathic remedy during the study
      period, with the highest prevalence to children under 12 months of age (9.5/1000
      children of that age). Children under the age of 16 made up 16% of the population
      prescribed homoeopathic remedies (2.2/1000 registered patients of that age).
      Three hundred and sixty-one patients (0.2/1000 registered patients) were
      prescribed at least one herbal remedy during the study period, 44 of whom were
      children < 16 years old. Patients prescribed a homoeopathic or herbal remedy were
      also prescribed a median of four and five conventional medicines, respectively.
      Of patients prescribed an oral herbal remedy, 4% were also concomitantly
      prescribed a conventional medicine with which a drug-herb interaction has been
      documented. CONCLUSIONS: Our study reports that a substantial number of Scottish
      general practitioners prescribe homoeopathic and herbal remedies, with an
      approximate doubling in the number of children prescribed homoeopathic remedies.
      The level of homoeopathic and herbal prescribing raises questions about
      homoeopathic/herbal provision in the National Health Service and should prompt
      critical review.

PMID- 16796703
TI  - An update on the first decade of the European centralized procedure: how many
      innovative drugs?
AB  - AIMS: In a previous paper, we proposed an algorithm to assess the degree of
      therapeutic innovation of the agents approved by the European centralized
      procedure, which must be followed by biotechnological products and is optional
      for drugs claimed as innovative. A low overall degree of therapeutic innovation
      (about 30%) was found. This figure may be an underestimate of the actual level of
      innovation, because common biotechnological products, such as recombinant human
      insulins, must follow this procedure. To test the hypothesis that therapeutic
      innovation prevails among nonbiotechnological products, we evaluated separately
      the degree of therapeutic innovation of biotechnological vs. nonbiotechnological
      agents in the first decade of European Medicines Agency activity, also studying a
      possible time trend. METHODS: We assessed, for each drug: (i) the seriousness of
      the target disease, (ii) the availability of previous treatments, and (iii) the
      extent of therapeutic effect according to the previously proposed algorithm.
      RESULTS: Our analysis considered 251 medicinal products corresponding to 198
      active substances, classified according to four main areas as therapeutic agents
      (88.9%), diagnostics (5.5%), vaccines (5.1%) and life-style drugs (0.5%). Among
      all therapeutic agents, 49 out of 176 agents (28%) were classified as having an
      important degree of therapeutic innovation. Fifteen out of 60 biotechnological
      therapeutic agents were considered important therapeutic innovations (25%),
      whereas this figure was 29% for nonbiotechnological agents. CONCLUSIONS: Among
      active substances claimed as innovative by the manufacturers, only a minority
      deserve this definition according to our algorithm.

PMID- 16796704
TI  - Prescribed doses of inhaled steroids in Dutch children: too little or too much,
      for too short a time.
AB  - AIMS: To investigate the dosage and duration of inhaled steroids prescribed to
      children and to compare the prescribed doses with recommended doses for the
      treatment of asthma in children. METHODS: For 2514 Dutch children aged 0-12 years
      who had used inhaled steroids in 2002, pharmacy dispensing data were obtained
      from the InterAction database, type of steroid (beclomethason, budesonide,
      fluticasone) and type of user (first time or existing) and the average prescribed
      doses according to age were determined and compared with the doses as recommended
      in the national Dutch Nederlands Huisartsen Genootschap (NHG) guideline.
      Furthermore, for all first-time users the duration of therapy with inhaled
      steroids was determined using a Kaplan-Meier analysis. RESULTS: The major
      findings were that: (i) overall 43% of children starting inhaled steroids were
      prescribed doses that are half the recommended dose or less; (ii) overall 8% of
      the children starting inhaled steroids were prescribed doses that were twice the
      recommended dose or more, up to 50% in the 12-year-olds fluticasone group; and
      (iii) only 8% of the children who started with inhaled steroids used them
      continuously for a full year. CONCLUSIONS: Doses of inhaled steroids for many
      children deviate from those recommended, with lower doses more frequently
      occurring than higher doses. Less than 10% of the children receive prescriptions
      for a prolonged period of time.

PMID- 16796705
TI  - Brain T1 intensity changes after levodopa administration in healthy subjects: a
      voxel-based morphometry study.
AB  - AIM: To test T1 intensity variations induced by levodopa administration in the
      regional fixation area in the human brain. METHOD: Using non-invasive magnetic
      resonance imaging (MRI) technique [T1-weighted sequence MPRAGE; TE/TR/TI =
      5/25/800 ms; impulsion angle = 15 degrees; field of view = 256 x 230 x 180 mm3;
      acquisition matrix = 256 x 192 x 104; reconstruction matrix = 256 x 256 x 128),
      we tested changes in the T1 MRI signal intensity resulting in changes in the grey
      matter automatic classification after administration of a single dose of 100 mg
      of levodopa by a voxel-based morphometry method (VBM) in 12 healthy subjects.
      RESULTS: The VBM analysis demonstrated an increased number of voxels attributed
      to grey matter after levodopa administration in an anatomical cluster which
      included substantia nigra, tegmental ventral area and subthalamic nucleus
      bilaterally, the principal origin and first relay nuclei of projections in brain
      dopaminergic systems (t = 8.61; corrected for all grey matter volume P < 0.001).
      CONCLUSION: Our results suggest that levodopa administration could induce an MRI
      T1 signal intensity variation that is not evident to the naked eye, but is
      detectable by measuring local signal intensities. Possible clinical applications
      are discussed.

PMID- 16796706
TI  - Effects of single and multiple doses of itraconazole on the pharmacokinetics of
      fexofenadine, a substrate of P-glycoprotein.
AB  - AIMS: We determined whether or not the extent of drug interaction of fexofenadine
      by itraconazole is time-dependent. METHODS: In a randomized two-phase crossover
      study, itraconazole was administered orally for 6 days, and, on days 1, 3 and 6,
      fexofenadine was administered simultaneously. On another occasion, fexofenadine
      was administered alone. RESULTS: Itraconazole increased fexofenadine AUC(0,
      infinity), and the % change for difference was 178% (95% CI 1235, 3379), 205%
      (95% CI 1539, 3319) and 169% (95% CI 1128, 2987) on days 1, 3 and 6 of the 6 day
      treatment, respectively. CONCLUSIONS: The extent of drug interaction by
      itraconazole was not time-dependent.

PMID- 16796707
TI  - Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide.
AB  - AIMS: Nateglinide is a meglitinide analogue with antidiabetic action. A recent
      study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP-C,
      OATP2) is a major determinant which markedly affects the pharmacokinetics of
      repaglinide. Our objective was to assess the association between single
      nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of
      nateglinide. METHODS: Seventeen healthy volunteers with different SLCO1B1
      genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in
      this study. Each was given a single oral dose of 90 mg nateglinide. Plasma
      concentrations of nateglinide were measured up to 8 h by HPLC. RESULTS: The
      C(max) and AUC(0,infinity) of nateglinide were 83% (P = 0.002) and 82% (P =
      0.001) higher in the SLCO1B1521TC subjects (n = 4), and 76% (P = 0.016) and 108%
      (P = 0.001) higher in the SLCO1B1521CC subjects (n = 2) than in the SLCO1B1521TT
      subjects (n = 11), respectively. The t(1/2) of nateglinide in SLCO1B1521CC
      subjects was 78% longer than that in 521TT subjects (P = 0.036). The difference
      in t(max) values among the three genotypic groups was not statistically
      significant. CONCLUSIONS: Our results suggest that OATP1B1-mediated hepatic
      uptake of nateglinide may be the prior step for its metabolism and elimination.
      SLCO1B1521T > C SNP might play an important role in the pharmacokinetics of
      nateglinide.

PMID- 16796708
TI  - Novel ADAMTS-13 mutations in an adult with delayed onset thrombotic
      thrombocytopenic purpura.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is associated with
      congenital and acquired deficiency of ADAMTS-13, a metalloprotease that cleaves
      von Willebrand factor (VWF) and reduces its adhesive activity. Mutations
      throughout the ADAMTS13 gene have been identified in congenital TTP patients,
      most of whom have initial episodes during infancy or in early childhood. PATIENTS
      AND METHODS: We report the case of an adult male who was diagnosed with
      idiopathic thrombocytopenic purpura at age 34, and with TTP 14 years later. The
      patient was compound heterozygous for an 18 bp in-frame deletion (C365del) in the
      disintegrin domain and a point mutation of R1060W in the seventh thrombospondin
      domain of the ADAMTS-13 gene. CONCLUSIONS: In vitro studies found that C365del
      and R1060W severely impair ADAMTS-13 synthesis in transfected Hela cells, whereas
      the deletion mutant also failed to cleave VWF under static and flow conditions.

PMID- 16796709
TI  - Bioavailability and relative tissue distribution of [125I]-recombinant human
      thrombin following intravenous or subcutaneous administration to non-human
      primates.
AB  - BACKGROUND: Recombinant human thrombin (rhThrombin) is being developed as a
      general adjunct to hemostasis. Endogenous thrombin is rapidly inactivated by
      complex formation with antithrombin III and other inhibitors. It follows that
      these inhibitors will also inactivate any rhThrombin that reaches the systemic
      circulation. OBJECTIVES: Study goals were to determine the pharmacokinetic
      characteristics of [(125)I]-rhThrombin and [(125)I]-rhThrombin complexed to
      endogenous inhibitors, and the tissue distribution of rhThrombin-associated
      radioactivity in non-human primates. Hematology, serum chemistry and coagulation
      status were also monitored. METHODS: [(125)I]-rhThrombin was administered
      intravenously (i.v.; 3.5 U kg(-1)) or subcutaneously (s.c.; 350 U kg(-1)) to male
      cynomolgus monkeys. Plasma was analyzed for rhThrombin-associated radioactivity
      and non-compartmental analysis was used to determine the corresponding
      pharmacokinetic parameters. A size exclusion-high pressure liquid chromatography
      (SE-HPLC) method was used to quantitate rhThrombin complexes, non-complexed
      rhThrombin, and free [(125)I]. Whole-body gamma scintigraphy was used to follow
      radioactivity localization up to 72 h postdose. RESULTS: No adverse events were
      observed following [(125)I]-rhThrombin administration. The pharmacokinetic
      profile of rhThrombin-associated radioactivity following i.v. injection was multi
      exponential with an initial half-life of approximately 10 min. Following both
      i.v. and s.c. dosing, the terminal half-life was approximately 15 h. SE-HPLC
      analysis revealed that rhThrombin was rapidly complexed to antithrombin III and
      other inhibitors in the systemic circulation following i.v. administration. Thus,
      rhThrombin-associated radioactivity in the blood was complexed and presumed
      inactive. [(125)I]-rhThrombin inhibitor complexes accumulated and were eliminated
      in the liver following both routes of administration. CONCLUSIONS: These data
      suggest that rhThrombin rapidly binds to endogenous inhibitors following either
      i.v. or s.c. administration.

PMID- 16796710
TI  - A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3
      mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism
      after colorectal surgery for cancer.
AB  - BACKGROUND: The optimal thromboprophylactic dosage regimen of low-molecular
      weight heparins in high-risk general surgery remains debatable. OBJECTIVES: We
      performed a randomized, double-blind study to compare the efficacy and safety of
      nadroparin 2850 IU (0.3 mL) and enoxaparin 4000 IU (40 mg) in the prevention of
      venous thromboembolism (VTE) after colorectal surgery for cancer. PATIENTS AND
      METHODS: Patients undergoing resection of colorectal adenocarcinoma were
      randomized to receive once daily either 2850 IU nadroparin or 4000 IU enoxaparin
      s.c. for 9 +/- 2 days. The primary efficacy outcome was the composite of deep
      vein thrombosis (DVT) detected by bilateral venography or documented symptomatic
      DVT or pulmonary embolism up to day 12. The main safety outcome was major
      bleeding. A blinded independent committee adjudicated all outcomes. RESULTS: Out
      of 1288 patients analyzed, efficacy was evaluable in 950 (73.8%) patients. The
      VTE rate was 15.9% (74/464) in nadroparin-treated patients and 12.6% (61/486) in
      enoxaparin-treated patients, a relative risk of 1.27 (95% confidence interval;
      CI: 0.93-1.74) that did not met the criterion for non-inferiority of nadroparin.
      The rate of proximal DVT was comparable in the two groups (3.2% vs. 2.9%,
      respectively), but that of symptomatic VTE was lower in nadroparin-treated
      patients (0.2% vs. 1.4%). There was significantly (P = 0.012) less major bleeding
      in nadroparin- than in enoxaparin-treated patients (7.3% vs. 11.5%,
      respectively). CONCLUSION: Compared with those receiving enoxaparin 4000 IU,
      patients treated with nadroparin 2850 IU showed a higher incidence of
      asymptomatic distal DVT, but a lower incidence of symptomatic VTE. Nadroparin
      treatment was safer in terms of bleeding risk.

PMID- 16796711
TI  - Functional analysis of two prothrombin 3'-untranslated region variants: the
      C20209T variant, mainly found among African-Americans, and the C20209A variant.

PMID- 16796712
TI  - Abnormal hemostasis tests and bleeding in chronic liver disease: are they
      related? No, but they need a careful look.

PMID- 16796713
TI  - Utility is not just posttransplant outcome!

PMID- 16796714
TI  - Cardiac assessment for renal transplantation should be evidence based.

PMID- 16796715
TI  - Liver transplantation for classical maple syrup urine disease.

PMID- 16796717
TI  - The significance of subclinical rejection and the value of protocol biopsies.
AB  - Subclinical rejection (SCR) is diagnosed by protocol histology with a maximal
      prevalence occurring early after transplantation, falling to low levels by 1
      year. Needle-core biopsy is safe, and the histology obtained fairly reflects
      subclinical immune activity. Several studies have consistently shown that SCR is
      associated with chronic tubulointerstitial damage, subsequent renal dysfunction
      and reduced graft survival. SCR is effectively treated by pulse corticosteroid
      therapy, although increased baseline immunosuppression may be necessary. A single
      randomized clinical trial of biopsy and corticosteroid therapy demonstrated
      significantly improved early structural and functional outcomes, and a
      (nonsignificant) 17% risk reduction in 4-year graft survival. Three possible
      approaches include: no protocol biopsies (usually accompanied by powerful
      immunosuppression); biopsies only in high-risk recipients (who may be difficult
      to reliably predict) or universal screening protocol biopsy (comprehensive but
      limited by cost and resource utilization). The appropriate screening methodology
      for a transplant unit is both a clinical and an economic decision; influenced by
      the SCR prevalence and potential gains of treatment, against costs and resource
      utilization. Further trials to quantify the cost-benefit balance in a typical,
      heterogeneous recipient population using modern immunosuppression are required.

PMID- 16796718
TI  - FK330, a novel inducible nitric oxide synthase inhibitor, prevents ischemia and
      reperfusion injury in rat liver transplantation.
AB  - Nitric oxide (NO), produced via inducible NO synthase (iNOS), is implicated in
      the pathophysiology of liver ischemia/reperfusion injury (IRI). We examined the
      effects of a novel iNOS inhibitor, FK330 (FR260330), in well-defined rat liver
      IRI models. In a model of liver cold ischemia followed by ex vivo reperfusion,
      treatment with FK330 improved portal venous flow, increased bile production and
      decreased hepatocellular damage. FK330 prevented IRI in rat model of 40-h cold
      ischemia followed by syngeneic orthotopic liver transplantation (OLT), as
      evidenced by: (1) increased OLT survival (from 20% to 80%); (2) decreased
      hepatocellular damage (serum glutamic oxaloacetic transaminase/glutamic pyruvic
      transaminase levels); (3) improved histological features of IRI; (4) reduced
      intrahepatic leukocyte infiltration, as evidenced by decreased expression of P
      selectin/intracellular adhesion molecule 1, ED-1/CD3 cells and neutrophils; (5)
      depressed lymphocyte activation, as evidenced by expression of pro-inflammatory
      cytokine (TNF-alpha, IL-1beta, IL-6) and chemokine (IP-10, MCP-1, MIP-2)
      programs; (6) prevented hepatic apoptosis and down-regulated Bax/Bcl-2 ratio.
      Thus, by modulating leukocyte trafficking and cell activation patterns, treatment
      of rats with FK330, a specific iNOS inhibitor, prevented liver IRI. These results
      provide the rationale for novel therapeutic approaches to maximize organ donor
      pool through the safer use of liver grafts despite prolonged periods of cold
      ischemia.

PMID- 16796719
TI  - Myeloma responses and tolerance following combined kidney and nonmyeloablative
      marrow transplantation: in vivo and in vitro analyses.
AB  - Six patients with renal failure due to multiple myeloma (MM) received
      simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical
      sibling donors following nonmyeloablative conditioning, including
      cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic
      irradiation. Cyclosporine (CyA) was given for approximately 2 months
      posttransplant, followed by donor leukocyte infusions. All six patients accepted
      their kidney grafts long-term. Three patients lost detectable chimerism but
      accepted their kidney grafts off immunosuppression for 1.3 to >7 years. One such
      patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in
      association with marrow rejection. Two patients achieved full donor chimerism,
      but resumed immunosuppression to treat graft-versus-host disease. Only one
      patient experienced rejection following CyA withdrawal. He responded to
      immunosuppression, which was later successfully withdrawn. The rejection episode
      was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness
      to cultured donor renal tubular epithelial cells. Initially recovering T cells
      were memory cells and were enriched for CD4+CD25+ cells. Three patients are in
      sustained complete remissions of MM, despite loss of chimerism in two. Combined
      kidney/BMT with nonmyeloablative conditioning can achieve renal allograft
      tolerance and excellent myeloma responses, even in the presence of donor marrow
      rejection and antidonor alloresponses in vitro.

PMID- 16796720
TI  - mTOR inhibition induces endothelial progenitor cell death.
AB  - Immunosuppressants are necessary to prevent graft rejection after solid organ
      transplantation. However, they are also known to have significant side effects,
      including endothelial toxicity. Endothelial progenitor cells originate in the
      bone marrow and are recognized by their angiogenic and endothelial reparative
      properties. The effects of the immunosuppressants cyclosporine A (CyA),
      tacrolimus and rapamycin were analyzed on endothelial progenitor-like cells.
      Rapamycin induced rapid cell death, even at concentrations much lower than those
      used clinically, in peripheral blood mononuclear cells (PBMC) cultured to favor
      outgrowth of endothelial progenitors. Cyclosporine A and tacrolimus had no
      significant effects at clinical concentrations. The effect of rapamycin was
      specific to endothelial progenitor cells, in particular to the early stages of
      differentiation, as a lesser effect was observed in late outgrowth endothelial
      progenitors, mature aortic endothelial cells, and macrophages derived from the
      same PBMCs. The mechanism of cell death appeared to be apoptosis; however, its
      induction was probably multifactorial and did not depend on caspase or cathepsin
      activation. In conclusion, rapamycin induces endothelial progenitor cell death,
      possibly because it blocks survival signals given by growth factors critically
      required by these cells.

PMID- 16796722
TI  - Myofibroblast transdifferentiation in obliterative bronchiolitis: tgf-beta
      signaling through smad3-dependent and -independent pathways.
AB  - We have shown that Smad3, an intracellular signal transducer for transforming
      growth factor-beta1 (TGF-beta1), is required to elicit the full histological
      manifestations of obliterative airway disease in a tracheal transplant model.
      This suggests that chronic allograft rejection results in TGF-beta1-induced Smad3
      activation that leads to airway obliteration through fibroproliferation and
      increased matrix deposition. In other systems, these latter events are causally
      related to the transdifferentiation of fibroblasts into myofibroblasts, but their
      role in obliterative bronchiolitis (OB) after lung transplantation is unknown. We
      confirmed the presence of myofibroblasts inside affected airways associated with
      experimental OB using immunohistochemistry. Studying airway fibroblasts in vitro,
      we observed increased myofibroblast transdifferentiation in response to TGF
      beta1, evidenced by increased alpha-smooth muscle actin mRNA and protein
      expression. In Smad3-null fibroblasts, TGF-beta1 induction of myofibroblast
      transdifferentiation was greatly diminished but not abolished, suggesting the
      presence of Smad3-independent pathways. Further studies revealed that small
      molecule inhibitors of p38 (SB203580) and MEK/ERK (U1026) further reduced the
      remaining effect of TGF-beta1 in Smad3-deficient fibroblasts. Together, these
      studies suggest that in chronic allograft rejection, TGF-beta1 stimulates
      myofibroblast transdifferentiation through Smad3-dependent and -independent
      signals, contributing to the excessive matrix deposition that characterizes
      obliterative bronchiolitis.

PMID- 16796721
TI  - Successful liver transplantation following medical management of portopulmonary
      hypertension: a single-center series.
AB  - Severe portopulmonary hypertension (POPH) is an absolute contraindication to
      orthotopic liver transplantation (OLT). Vasodilators have been used, but the
      safety of subsequent transplantation and the reversibility of pulmonary
      hypertension after transplantation are uncertain. This study examined the
      feasibility and post-transplant effects of liver transplantation following
      medical control of POPH. Eight consecutive patients (three females and five
      males, ages 39-51) with POPH as their only contraindication to transplantation
      were treated with continuous intravenous epoprostenol. Liver transplantation was
      considered if the mean pulmonary artery pressure (PAM) was lowered to <35 mmHg.
      Epoprostenol 2-8 ng/kg/min successfully improved hemodynamics in seven of eight
      patients, usually within 6.5 months of initiating therapy. PAM declined from an
      average of 43-33 mmHg (p=0.03); mean pulmonary vascular resistance declined from
      410 to 192 dyn s cm-5 (p=0.01) and cardiac output increased from 6.6 to 10 L/min
      (p=0.02). Six of the seven responders were actively listed for liver
      transplantation. Two died on the waiting list; the remaining four were
      transplanted and remain alive and well 9-18 months post-OLT-two without
      vasodilators, and two on oral medication. We conclude that pulmonary vasodilators
      permit safe liver transplantation in some cases, and that POPH may be reversible
      after transplantation.

PMID- 16796724
TI  - MiHA reactive CD4 and CD8 T-cells effect resistance to hematopoietic engraftment
      following reduced intensity conditioning.
AB  - Reduced intensity conditioning (RIC) prior to allogeneic hematopoietic cell
      transplantation (HCT) has shown promise in lowering the incidence of post
      transplant complications including infection and graft-versus-host disease. T
      cell-mediated graft rejection, however, remains a crucial factor in determining
      how 'mild' a level of immunosuppression can be administered. Understanding the
      kinetics of resistance responses as well as the role of CD4+ and CD8+ T cells
      underlies the development of protocols to circumvent resistance and support
      hematopoietic engraftment. In these studies, a major histocompatibility complex
      (MHC)-matched/minor histocompatibility antigen (MiHA) disparate RIC HCT model was
      developed in which resistance against donor hematopoietic progenitors as well as
      mature peripheral blood cells could be assessed. Interestingly, resistance was
      diminished in the absence of either host CD4+ or CD8+ T cells. However, its
      impairment was more severe in CD4-/- mice where resistance was not detected. Host
      CD4+ T cells were required for optimal expansion of specific (H60) T-cell
      receptor (TCR) expressing host anti-donor MiHA reactive CD8+ T cells following
      HCT. These observations demonstrate a critical role for host CD4+ T cells in
      resistance against MiHA disparate HCT. This RIC HCT resistance model will be
      useful for the analysis of the barrier to engraftment mediated by host T cells
      and the development of strategies to support engraftment.

PMID- 16796723
TI  - Successful in vitro priming of EBV-specific CD8+ T cells endowed with strong
      cytotoxic function from T cells of EBV-seronegative children.
AB  - Epstein-Barr virus (EBV)-seronegative transplant recipients are at high risk of
      developing EBV-associated post-transplant lymphoproliferative disorder (PTLD),
      and would maximally benefit from an EBV-directed T-cell therapy for prevention or
      treatment of PTLD. So far, efforts to activate CD8+ EBV-specific cytotoxic T
      lymphocytes (CTL) endowed with high specific cytotoxicity from EBV-seronegative
      children have failed. We compared the CD8+ CTL priming efficiency of three
      different modified activation protocols, based on lymphoblastoid cell lines (LCL)
      stimulation potentially enhanced by either LCL presentation through dendritic
      cells, or selection of IFN-gamma+ cultured cells, or culture in the presence of
      rhIL-12 and rhIL-7, according to the standard protocol for reactivation of EBV
      specific CTL. We found that only specific LCL stimulation in the presence of rhIL
      12 and rhIL-7 was able to reproducibly expand EBV-specific CD8+ CTL endowed with
      strong cytotoxic activity from truly EBV-seronegative children. The lines thus
      activated, which included specificities toward EBV latent and lytic proteins,
      showed high percentage CD8+ T cells, with <10% naive CD8+/CCR7+/CD45RA+ cells.
      Overall, the total number of CD8+ central memory cells, and of CCR7 T-cell
      effectors was comparable to that observed in healthy EBV-seropositive controls.
      In conclusion, it is feasible to activate EBV-specific CD8+ CTL with suitable
      characteristics for in vivo employment from EBV-seronegative children.

PMID- 16796726
TI  - Striving for perfection: evaluation of the right lobe live liver donor.

PMID- 16796727
TI  - Reflux of bile acids: an innate problem of lung transplantation.

PMID- 16796725
TI  - Preventing renal ischemia-reperfusion injury using small interfering RNA by
      targeting complement 3 gene.
AB  - The complement system is one of the important mediators of renal ischemia
      reperfusion injury (IRI). We hypothesized that efficient silencing of C3, which
      is the central component on which all complement activation pathways converge,
      could be achieved using small interfering RNA (siRNA), and that this would result
      in overall inhibition of complement activation, thereby preventing IRI in
      kidneys. A series of experiments was conducted, using a mouse model of IRI and
      vector-delivered C3-specific siRNA. We demonstrated the following: (1) renal
      expression of C3 increases as a result of IRI; (2) by incorporation into a pRNAT
      U6.1 vector, siRNA can be delivered to renal cells in vivo; (3) systemically
      delivered siRNA is effective in reducing the expression of C3 in an
      experimentally induced mouse kidney model of IRI; (4) similarly, siRNA reduces
      complement-mediated IRI-related effects, both in terms of renal injury (as
      evidenced by renal function and histopathology examination) and mouse mortality
      and (5) silencing the production of C3 diminishes in vivo production of TNF
      alpha. This study implies that siRNA represents a novel approach to preventing
      IRI in kidneys and might be used in a variety of clinical settings, including
      transplantation and acute tubular necrosis.

PMID- 16796728
TI  - Role of placental growth factor in glucose metabolism.

PMID- 16796729
TI  - Risk factors and immunological pathways for asthma and other allergic diseases in
      children: background and methodology of a longitudinal study in a large urban
      center in Northeastern Brazil (Salvador-SCAALA study).
AB  - BACKGROUND: The prevalence of asthma and allergic diseases has increased in
      industrialised countries, and it is known that rates vary according whether the
      area is urban or rural and to socio-economic status. Surveys conducted in some
      urban settings in Latin America found high prevalence rates, only exceeded by the
      rates observed in industrialised English-speaking countries. It is likely that
      the marked changes in the environment, life style and living conditions in Latin
      America are responsible for these observations. The understanding of the
      epidemiological and immunological changes that underlie the increase in asthma
      and allergic diseases in Latin America aimed by SCAALA studies in Brazil and
      Ecuador will be crucial for the identification of novel preventive interventions.
      METHODS/DESIGN: The Salvador-SCAALA project described here is a longitudinal
      study involving children aged 4-11 years living in the city of Salvador,
      Northeastern Brazil. Data on asthma and allergic diseases (rhinitis and eczema)
      and potential risk factors will be collected in successive surveys using
      standardised questionnaire. This will be completed with data on dust collection
      (to dust mite and endotoxin), skin test to most common allergens, stool
      examinations to helminth and parasites, blood samples (to infection, total and
      specific IgE, and immunological makers), formaldehyde, physical inspection to
      diagnoses of eczema, and anthropometric measures. Data on earlier exposures when
      these children were 0-3 years old are available from a different project.
      DISCUSSION: It is expected that knowledge generated may help identify public
      health interventions that may enable countries in LA to enjoy the benefits of a
      "modern" lifestyle while avoiding--or minimising--increases in morbidity caused
      by asthma and allergies.

PMID- 16796730
TI  - Superior efficacy of St John's wort extract WS 5570 compared to placebo in
      patients with major depression: a randomized, double-blind, placebo-controlled,
      multi-center trial [ISRCTN77277298].
AB  - BACKGROUND: The aim of the current study was to assess the antidepressant
      efficacy and safety of Hypericum perforatum (St. John's wort) extract WS 5570 at
      doses of 600 mg/day in a single dose and 1200 mg/day in two doses. METHODS: The
      participants in this double-blind, randomized, placebo-controlled, multi-center
      clinical trial were male and female adult out-patients with an episode of mild or
      moderate major depressive episode (single or recurrent episode, DSM-IV criteria).
      As specified by the relevant guideline, the study was preceded by a medication
      free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to
      WS 5570 600 mg/day, 127 to WS 5570 1200 mg/day, and 82 to placebo. The primary
      outcome measure was the change in total score on the Hamilton Rating Scale for
      Depression (HAM-D, 17-item version) between baseline and endpoint. Additional
      measures included the number of responders, the number of patients in remission,
      and several other standard rating scales. Efficacy and safety were assessed after
      2 and 6 weeks. The design included an interim analysis performed after
      randomization with the option of early termination. RESULTS: After 6 weeks of
      treatment, mean +/- standard deviation decreases in HAM-D total scores of 11.6 +/
      6.4, 10.8 +/- 7.3, and 6.0 +/- 8.1 points were observed for the WS 5570 600
      mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis).
      Secondary measures of treatment efficacy also showed that both WS 5570 groups
      were statistically superior to placebo. Significantly more patients in the WS
      5570 treatment groups than in the placebo group showed treatment response and
      remission. WS 5570 was consistently more effective than placebo in patients with
      either less severe or more severe baseline impairment. The number of patients who
      experienced remission was higher in the WS 5570 1200 mg/day group than the WS
      5570 600 mg/day group. The incidence of adverse events was low in all groups. The
      adverse event profile was consistent with the known profile for Hypericum extract
      preparations. CONCLUSION: Hypericum perforatum extract WS 5570 at doses of 600
      mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe
      and more effective than placebo, with comparable efficacy of the WS 5570 groups
      for the treatment of mild to moderate major depression.

PMID- 16796732
TI  - U.S. congressional district cancer death rates.
AB  - BACKGROUND: Geographic patterns of cancer death rates in the U.S. have
      customarily been presented by county or aggregated into state economic or health
      service areas. Herein, we present the geographic patterns of cancer death rates
      in the U.S. by congressional district. Many congressional districts do not follow
      state or county boundaries. However, counties are the smallest geographical units
      for which death rates are available. Thus, a method based on the hierarchical
      relationship of census geographic units was developed to estimate age-adjusted
      death rates for congressional districts using data obtained at county level.
      These rates may be useful in communicating to legislators and policy makers about
      the cancer burden and potential impact of cancer control in their jurisdictions.
      RESULTS: Mortality data were obtained from the National Center for Health
      Statistics (NCHS) for 1990-2001 for 50 states, the District of Columbia, and all
      counties. We computed annual average age-adjusted death rates for all cancer
      sites combined, the four major cancers (lung and bronchus, prostate, female
      breast, and colorectal cancer) and cervical cancer. Cancer death rates varied
      widely across congressional districts for all cancer sites combined, for the four
      major cancers, and for cervical cancer. When examined at the national level,
      broad patterns of mortality by sex, race and region were generally similar with
      those previously observed based on county and state economic area. CONCLUSION: We
      developed a method to generate cancer death rates by congressional district using
      county-level mortality data. Characterizing the cancer burden by congressional
      district may be useful in promoting cancer control and prevention programs, and
      persuading legislators to enact new cancer control programs and/or strengthening
      existing ones. The method can be applied to state legislative districts and other
      analyses that involve data aggregation from different geographic units.

PMID- 16796731
TI  - Live bacterial vaccines--a review and identification of potential hazards.
AB  - The use of live bacteria to induce an immune response to itself or to a carried
      vaccine component is an attractive vaccine strategy. Advantages of live bacterial
      vaccines include their mimicry of a natural infection, intrinsic adjuvant
      properties and their possibility to be administered orally. Derivatives of
      pathogenic and non-pathogenic food related bacteria are currently being evaluated
      as live vaccines. However, pathogenic bacteria demands for attenuation to weaken
      its virulence. The use of bacteria as vaccine delivery vehicles implies
      construction of recombinant strains that contain the gene cassette encoding the
      antigen. With the increased knowledge of mucosal immunity and the availability of
      genetic tools for heterologous gene expression the concept of live vaccine
      vehicles gains renewed interest. However, administration of live bacterial
      vaccines poses some risks. In addition, vaccination using recombinant bacteria
      results in the release of live recombinant organisms into nature. This places
      these vaccines in the debate on application of genetically modified organisms. In
      this review we give an overview of live bacterial vaccines on the market and
      describe the development of new live vaccines with a focus on attenuated bacteria
      and food-related lactic acid bacteria. Furthermore, we outline the safety
      concerns and identify the hazards associated with live bacterial vaccines and try
      to give some suggestions of what to consider during their development.

PMID- 16796733
TI  - Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by
      IVF (for IUI failures) in couples with unexplained or mild male factor
      subfertility.
AB  - BACKGROUND: In unexplained and mild male factor subfertility, both intrauterine
      insemination (IUI) and in-vitro fertilisation (IVF) are indicated as first line
      treatments. Because the success rate of IUI is low, many couples failing IUI
      subsequently require IVF treatment. In practice, it is therefore important to
      examine the comparative outcomes (live birth-producing pregnancy), costs, and
      cost-effectiveness of primary offer of IVF, compared with primary offer of IUI
      followed by IVF for couples failing IUI. METHODS: Mathematical modelling was used
      to estimate comparative clinical and cost effectiveness of either primary offer
      of one full IVF cycle (including frozen cycles when applicable) or "IUI + IVF"
      (defined as primary IUI followed by IVF for IUI failures) to a hypothetical
      cohort of subfertile couples who are eligible for both treatment strategies. Data
      used in calculations were derived from the published peer-reviewed literature as
      well as activity data of local infertility units. RESULTS: Cost-effectiveness
      ratios for IVF, "unstimulated-IUI (U-IUI) + IVF", and "stimulated IUI (S-IUI) +
      IVF" were 12,600 pounds sterling, 13,100 pound sterling and 15,100 pound sterling
      per live birth-producing pregnancy respectively. For a hypothetical cohort of 100
      couples with unexplained or mild male factor subfertility, compared with primary
      offer of IVF, 6 cycles of "U-IUI + IVF" or of "S-IUI + IVF" would cost an
      additional 174,200 pounds sterling and 438,000 pounds sterling, representing an
      opportunity cost of 54 and 136 additional IVF cycles and 14 to 35 live birth
      producing pregnancies respectively. CONCLUSION: For couples with unexplained and
      mild male factor subfertility, primary offer of a full IVF cycle is less costly
      and more cost-effective than providing IUI (of any modality) followed by IVF.

PMID- 16796734
TI  - Effect of three different cultivars of Lepidium meyenii (Maca) on learning and
      depression in ovariectomized mice.
AB  - BACKGROUND: Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian
      hypocotyl growing exclusively between 4000 and 4500 m altitude in the central
      Peruvian Andes, particularly in Junin plateau and is used traditionally to
      enhance fertility. Maca is a cultivated plant and different cultivars are
      described according to the color of the hypocotyls. METHODS: The study aimed to
      elucidate the effect of Yellow, Red and Black Maca on cognitive function and
      depression in ovariectomized (OVX) mice. In all experiments OVX mice were treated
      during 21 days and divided in four groups: control group, Yellow Maca, Red Maca
      and Black Maca. Latent learning was assessed using the water finding task and the
      antidepressant activity of the three varieties of Maca was evaluated using the
      forced swimming test. Animals were sacrificed at the end of each treatment and
      the uterus were excised and weighed. RESULTS: Black Maca was the variety that
      showed the best response in the water finding task, particularly in the trained
      mice. The three varieties were effective to reduce finding latency in non trained
      and trained mice (P < 0.05). In the force swimming test, all varieties assessed
      reduced the time of immobility and increased uterine weight in OVX mice.
      CONCLUSION: Black Maca appeared to have more beneficial effects on latent
      learning in OVX mice; meanwhile, all varieties of Maca showed antidepressant
      activity.

PMID- 16796735
TI  - Pattern of mRNA expression of beta-defensins in basal cell carcinoma.
AB  - BACKGROUND: Although the human beta-defensins hBDs today seem to have diverse
      functional activities in innate antimicrobial immunity, a few reports also
      indicated an altered expression of these antimicrobial peptides (AMPs) in tissues
      of cancers such as oral squamous cell carcinoma. The present work was aimed on
      the study of hBD gene expression in basal cell carcinoma (BCC) which is the most
      common cancer in humans. METHODS: Twenty-two non-ulcerated BCCs (12 nodular type,
      10 superficial type) have been analysed for the presence of hBD (1-3) mRNA by
      quantitative real-time RT-PCR. As controls, non-lesional skin specimens of BCC
      patients as well as samples of healthy subjects were assessed by RT-PCR. RESULTS:
      hBD-1 levels in healthy controls and non-lesional skin of BCC patients were
      significantly (P < 0.05) higher than the levels observed in tumour tissue.
      Moreover, BCCs showed significantly (P < 0.05) increased mRNA expression of hBD-2
      as compared to controls. There was no significant (P > 0.05) difference between
      lesional mRNA levels for hBD-3 and those levels observed in controls. The mRNA
      expression of hBDs (1-3) found in nodular and superficial BCCs did not
      significantly (P > 0.05) differ. CONCLUSION: The gene expression patterns of hBD
      1 and hBD-2 are for the first time shown to be significantly altered in non
      ulcerated BCCs as compared to intra-individual and inter-individual controls,
      respectively. The present findings may indicate that beside the antimicrobial
      activity of AMPs, hBDs may also play a role in the pathogenesis of BCC. However,
      functional and immunohistological studies investigating hBDs in patients with BCC
      are needed to confirm our data.

PMID- 16796736
TI  - Healing of bronchopleural fistula using a modified Dumon stent: a case report.
AB  - BACKGROUND: Bronchopleural fistula following lung resection is a therapeutic
      challenge for thoracic surgeons. CASE PRESENTATION: We describe a case of late
      bronchopleural fistula after right extrapleural pneumonectomy for malignant
      mesothelioma. Bronchoscopic attempts to repair it were unsuccessful. CONCLUSION:
      The use of a modified Y Dumon stent associated with glue apposition on the
      bronchial stump allowed us to close the fistula without the need of any surgical
      repair.

PMID- 16796737
TI  - Trimellitic anhydride-conjugated serum albumin activates rat alveolar macrophages
      in vitro.
AB  - BACKGROUND: Occupational exposure to airborne low molecular weight chemicals,
      like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar
      macrophages (AMs) are among the first cells to encounter these inhaled compounds
      and were previously shown to influence TMA-induced asthma-like symptoms in the
      Brown Norway rat. TMA is a hapten that will bind to endogenous proteins upon
      entrance of the body. Therefore, in the present study we determined if TMA and
      TMA conjugated to serum albumin induced the production of the macrophage
      mediators nitric oxide (NO), tumour necrosis factor (TNF), and interleukin 6 (IL
      6) in vitro using the rat AM cell line NR8383 and primary AMs derived from TMA
      sensitized and naive Brown Norway rats. METHODS: Cells were incubated with
      different concentrations of TMA, TMA conjugated to bovine serum albumin (BSA),
      and BSA as a control for 24 h and the culture supernatant was analyzed for
      mediator content. RESULTS: TMA alone was not able to induce the production of
      mediators by NR8383 cells and primary AMs from sensitized and sham-treated rats.
      TMA-BSA, on the contrary, dose-dependently stimulated the production of NO, TNF,
      and IL-6 by NR8383 cells and of NO and TNF, but not IL-6, by primary AMs
      independent of sensitization. CONCLUSION: Results suggest that although TMA is a
      highly reactive compound, conjugation to a suitable protein is necessary to
      induce mediator production by AMs. Furthermore, the observation that effects of
      TMA-BSA were independent of sensitization suggests involvement of an
      immunologically non-specific receptor. In the discussion it is argued that a
      macrophage scavenger receptor is a likely candidate.

PMID- 16796738
TI  - Prevalence and predictors of tuberculin skin positivity in Hellenic Army
      recruits.
AB  - BACKGROUND: Tuberculosis (TB) remains one of the leading causes of death among
      infectious diseases worldwide. Despite its low incidence rates in countries of
      Western Europe and North America, the resurgence of TB in Eastern Europe and the
      increased immigration from high-incidence countries imply that extreme vigilance
      is required in order to detect early, treat, and isolate all new cases. In this
      study, we analyzed the prevalence and predictors of tuberculin skin testing
      positivity in Hellenic Army recruits. METHODS: The study population consisted of
      953 Greek military recruits enlisted inthe Army during the period from November
      2005 to February 2006. Tuberculin skin testing was performed on all study
      subjects upon enrollment, according to the routine procedures. A tuberculin skin
      test reaction size >15 mm was considered positive for all study participants.
      Epidemiological data regarding age, repatriation status, geographic area of
      residence, smoking habits, and parental occupation were collected by means of
      personal interviews. In addition, body weight, height, and body mass index were
      measured. RESULTS: The mean age of the studied subjects (+/- SD) was 23.5 (+/-
      6.4) years. The overall prevalence of tuberculin positivity was 3.9% (37/953),
      and bivariable analysis showed that it was associated with lower weight (p =
      0.047) and repatriation status (p < 0.001). Tuberculin skin testing was positive
      in 2.6% of natives (24/900) and 24.5% of repatriates (13/53). A backward,
      stepwise multivariable logistic regression model showed that only repatriation
      status was independently associated with tuberculin positivity (p < 0.001; odds
      ratio [OR]: 14.1; 95% confidence interval [CI]: 6.5-30.3). CONCLUSION: While the
      incidence of tuberculosis in the native Greek population is low, and comparable
      to other Western European countries, the extremely high tuberculin positivity in
      repatriated persons underscores the importance of actively screening for TB in
      order to promptly identify, isolate, and treat cases of active and latent
      infection.

PMID- 16796739
TI  - Protection of rabbits against enteropathogenic Escherichia coli (EPEC) using an
      intimin null mutant.
AB  - BACKGROUND: Diarrhea and mortality resulting from infections with
      enteropathogenic Escherichia coli (EPEC) are of major economic importance in the
      rabbit meat industry. There is a growing need for an effective vaccine to cope
      with these problems and to reduce the use of antibiotics. EPEC are characterized
      by an attaching and effacing virulence mechanism. This is partly mediated by the
      intimate binding between an adhesin, called intimin, and a translocated receptor
      (Tir) of prokaryote origin. We constructed an intimin deletion mutant of the
      rabbit EPEC (REPEC) wild-type strain 97/241.6 (bio-/serogroup 3-/O15) and
      examined its protective capacity. RESULTS: After verifying its complete loss of
      virulence, we used the attenuated strain in vaccination-challenge experiments in
      which complete protection against a homologous, but virulent, strain was
      observed. The attenuated strain was able to persist in the intestinal lumen,
      where it elicited an immune response against EPEC-related virulence proteins, as
      was shown using an EspB-specific ELISA. Despite the priming of an immune response
      and the generation of specific antibodies, the intimin mutant was not able to
      fully protect rabbits against challenges with REPEC strains of other bio
      /serogroups. CONCLUSION: These data indicate that protection against REPEC
      infections is at least partly bio-/serogroup dependent and a multivalent vaccine
      may be needed for protection against the full range of REPEC types. Such a
      combination vaccine may be developed using intimin null mutants, as the latter
      were clearly shown to be safe and effective against homologous infections.

PMID- 16796740
TI  - The role of major duct excision and microdochectomy in the detection of breast
      carcinoma.
AB  - BACKGROUND: The association of nipple discharge with breast carcinoma has
      resulted in numerous women undergoing exploratory surgery to exclude malignancy.
      The aim of this study was to determine whether pre-operative factors can identify
      those patients that are most at risk of carcinoma. METHODS: All patients over a
      14-year period (1991-2005) who had a microdochectomy or subareolar exploration
      for the evaluation of nipple discharge were assessed. Patient characteristics,
      pre-operative imaging and pathological findings were analysed. RESULTS: Of the
      211 patients included in this study, 116 patients had pathological (unilateral,
      uniductal serous or bloody) discharge. On excision, 6% (n = 7) of patients with
      pathological discharge and 2.4% (n = 2) of patients with non-pathological
      discharge were diagnosed with carcinoma. Overall, major duct excision resulted in
      the diagnosis of carcinoma in 4.3% (n = 9), ADH/LCIS in 4% (n = 8), papilloma in
      39% (n = 83), and duct ectasia or non-specific benign disease in 53% (n = 111) of
      patients. In the patients determined to have malignancy, 44% (n = 4) were
      premenopausal. No patient with a non-bloody discharge in the total population
      analysed (28%; n = 59/211), or in the population with a pathological discharge
      (21%; n = 24/116) was found to have carcinoma upon excision. CONCLUSION:
      Microdochectomy or major duct excision performed for nipple discharge resulted in
      a low rate of malignancy on excision. Conservative management of non-bloody
      nipple discharge can be considered in patients with no other clinical or
      radiological signs of malignancy.

PMID- 16796741
TI  - Nosocomial infection in a newborn intensive care unit (NICU), South Korea.
AB  - BACKGROUND: This study aimed to determine the occurrence of nosocomial infections
      (NIs), including infection rates, main infection sites, and common
      microorganisms. Patients included in the study were taken from a newborn
      intensive care unit (NICU), in a hospital in South Korea. METHODS: A
      retrospective cohort study was performed by reviewing chart. The subjects were
      489 neonates who were admitted to the NICU, survived longer than 72 hours, and
      not transferred to another unit, between Jan. 1. 1995 to Sep. 30, 1999. NIs were
      identified according to the NNIS definition. Data were analyzed with descriptive
      statistics. RESULTS: Cumulative incidence rate for NIs was 30.3 neonates out of
      100 admissions, with a total of 44.6 infections. The incidence density was
      average 10.2 neonates and 15.1 infections per 1000 patient days. The most common
      infections were pneumonia (28%), bloodstream infection (26%), and conjunctivitis
      (22%). Major pathogens were Gram-positives such as Staphylococcus aureus and
      coagulase-negative staphylococci. The factors associated with NI was less than
      1500 g of birth weight, less than 32 weeks of gestational age, and less than 8 of
      apgar score. There's no statistical difference in discharge status between two
      groups, but hospital stay was longer in subjects with nosocomial infection than
      those without infection. CONCLUSION: Although the distribution of pathogens was
      similar to previous reports, a high rate of nosocomial infection and in
      particular conjunctivitis was observed in this study that merits further
      evaluation.

PMID- 16796743
TI  - Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1
      diabetes: a case control study.
AB  - BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial
      disease characterized by abnormal metabolism of carbohydrate and fat. Diminished
      carnitine plasma levels have been previously reported in T1D patients and
      carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the
      carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been
      involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis
      and Crohn's disease. For these reasons, we investigated for the first time the
      association with T1D of six single nucleotide polymorphisms (SNPs) mapping to
      these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2
      intron. METHODS: A case-control study was performed in the Spanish population
      with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood
      haplotype frequencies were estimated by applying the Expectation-Maximization
      (EM) algorithm implemented by the Arlequin software. RESULTS: When independently
      analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed
      significant association with T1D in our Spanish cohort. The overall comparison of
      the inferred haplotypes was significantly different between patients and controls
      (chi2 = 10.43; p = 0.034) with one of the haplotypes showing a protective effect
      for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41-0.93); p =
      0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus
      seems to be significantly different between T1D patients and controls; however,
      additional studies in independent populations would allow to confirm the role of
      these genes in T1D risk.

PMID- 16796742
TI  - Deciphering protein function during mitosis in PtK cells using RNAi.
AB  - BACKGROUND: Studying mitosis requires a system in which the dramatic movements of
      chromosomes and spindle microtubules can be visualized. PtK cells, due to their
      flat morphology and their small number of large chromosomes, allow microscopic
      visualizations to be readily performed. RESULTS: By performing RNAi in PtK cells,
      we can explore the function of many proteins important for spindle assembly and
      chromosome segregation. Although it is difficult to transfect DNA into PtK cells
      (efficiency approximately 10%), we have transfected a fluorescent siRNA at nearly
      100% efficiency. Using a cDNA expression library, we then isolated a complete PtK
      MCAK (P-MCAK) cDNA. P-MCAK shares 81% identity to Human-MCAK (H-MCAK) protein and
      66% identity to H-MCAK DNA. Knockdown of P-MCAK by RNAi caused defects in
      chromosome congression and defective spindle organization. Live imaging revealed
      that chromosomes had defects in congression and segregation, similar to what we
      found after microinjection of inhibitory anti-MCAK antibodies. Because it is
      laborious to isolate full-length clones, we explored using RT-PCR with degenerate
      primers to yield cDNA fragments from PtK cells from which to design siRNAs. We
      isolated a cDNA fragment of the mitotic kinesin Eg5 from PtK cells. This fragment
      is 93% identical to H-Eg5 protein and 87% identical to H-Eg5 DNA. A conserved 21
      bp siRNA was used for RNAi in both HeLa and PtK cells in which Eg5 knockdown
      resulted in an increased mitotic index and cells with monopolar spindles. In
      addition, we used RT-PCR to isolate fragments of 5 additional genes, whose
      sequence identity ranged from 76 to 90% with human, mouse, or rat genes,
      suggesting that this strategy is feasible to apply to any gene of interest.
      CONCLUSION: This approach will allow us to effectively probe mitotic defects from
      protein knockdowns by combining genomic information from other organisms with the
      tractable morphology of PtK cells.

PMID- 16796745
TI  - Protein disorder prediction by condensed PSSM considering propensity for order or
      disorder.
AB  - BACKGROUND: More and more disordered regions have been discovered in protein
      sequences, and many of them are found to be functionally significant. Previous
      studies reveal that disordered regions of a protein can be predicted by its
      primary structure, the amino acid sequence. One observation that has been widely
      accepted is that ordered regions usually have compositional bias toward
      hydrophobic amino acids, and disordered regions are toward charged amino acids.
      Recent studies further show that employing evolutionary information such as
      position specific scoring matrices (PSSMs) improves the prediction accuracy of
      protein disorder. As more and more machine learning techniques have been
      introduced to protein disorder detection, extracting more useful features with
      biological insights attracts more attention. RESULTS: This paper first studies
      the effect of a condensed position specific scoring matrix with respect to
      physicochemical properties (PSSMP) on the prediction accuracy, where the PSSMP is
      derived by merging several amino acid columns of a PSSM belonging to a certain
      property into a single column. Next, we decompose each conventional
      physicochemical property of amino acids into two disjoint groups which have a
      propensity for order and disorder respectively, and show by experiments that some
      of the new properties perform better than their parent properties in predicting
      protein disorder. In order to get an effective and compact feature set on this
      problem, we propose a hybrid feature selection method that inherits the
      efficiency of uni-variant analysis and the effectiveness of the stepwise feature
      selection that explores combinations of multiple features. The experimental
      results show that the selected feature set improves the performance of a
      classifier built with Radial Basis Function Networks (RBFN) in comparison with
      the feature set constructed with PSSMs or PSSMPs that adopt simply the
      conventional physicochemical properties. CONCLUSION: Distinguishing disordered
      regions from ordered regions in protein sequences facilitates the exploration of
      protein structures and functions. Results based on independent testing data
      reveal that the proposed predicting model DisPSSMP performs the best among
      several of the existing packages doing similar tasks, without either under
      predicting or over-predicting the disordered regions. Furthermore, the selected
      properties are demonstrated to be useful in finding discriminating patterns for
      order/disorder classification.

PMID- 16796744
TI  - Tumour necrosis factor-alpha stimulates HIV-1 replication in single-cycle
      infection of human term placental villi fragments in a time, viral dose and
      envelope dependent manner.
AB  - BACKGROUND: The placenta plays an important role in the control of in utero HIV-1
      mother-to-child transmission (MTCT). Proinflammatory cytokines in the placental
      environment are particularly implicated in this control. We thus investigated the
      effect of TNF-alpha on HIV-1 expression in human placental tissues in vitro.
      RESULTS: Human placental chorionic villi fragments were infected with varying
      doses of luciferase reporter HIV-1 pseudotypes with the R5, X4-Env or the
      vesicular stomatitis virus protein G (VSV-G). Histocultures were then performed
      in the presence or absence of recombinant human TNF-alpha. Luciferase activity
      was measured at different time points in cell lysates or on whole fragments using
      ex vivo imaging systems.A significant increase in viral expression was detected
      in placental fragments infected with 0.2 ng of p24 antigen/fragment (P = 0.002)
      of VSV-G pseudotyped HIV-1 in the presence of TNF-alpha seen after 120 hours of
      culture. A time independent significant increase of viral expression by TNF-alpha
      was observed with higher doses of VSV-G pseudotyped HIV-1. When placental
      fragments were infected with R5-Env pseudotyped HIV-1, a low level of HIV
      expression at 168 hours of culture was detected for 3 of the 5 placentas tested,
      with no statistically significant enhancement by TNF-alpha. Infection with X4-Env
      pseudotyped HIV-1 did not lead to any detectable luciferase activity at any time
      point in the absence or in the presence of TNF-alpha. CONCLUSION: TNF-alpha in
      the placental environment increases HIV-1 expression and could facilitate MTCT of
      HIV-1, particularly in an inflammatory context.

PMID- 16796746
TI  - Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus
      in rabbits fed a supplemental cholesterol diet.
AB  - BACKGROUND: Vascular calcification is implicated in myocardial infarction,
      instability and rigidity of the aortic wall, and bioprosthetic failures. Although
      an increase in the calcium (Ca) content in atherogenic diets has been shown to
      decrease atherosclerosis in rabbits, whether Ca supplementation and deficiency
      can affect atherosclerosis-related aortic calcification remains unknown. RESULTS:
      New Zealand White male rabbit littermates were fed an atherogenic diet containing
      0.5% cholesterol and 2% peanut oil. The Ca content of the diet, which normally
      contains 1%, was adjusted to 0.5 or 3%. Segments of thoracic aortas were
      dissected from rabbits for histological evaluations and Ca and Pi determinations.
      Rabbits with calcium supplementation were maintained for 4 months, whereas those
      with calcium deficiency were maintained for 2 1/2 months due to severe icterus
      beyond this stage. The ratios of intimal to medial areas and calcified to intimal
      areas were used to semi-quantify lesion accumulation and calcification,
      respectively. Icterus was estimated from the extent of yellowing of the skin,
      sclera, and mucous membranes along with gross evidence of hepatic lipidosis
      and/or biliary obstructions. Statistical analysis of 16 matched littermates shows
      that Ca supplementation significantly decreased the lesions by 41% (p < 0.05) and
      markedly inhibited calcification by 62% (p < 0.05). Statistical analysis of 11
      matched littermates shows that Ca deficiency significantly increased the lesions
      by 2.7-fold (p < 0.05) and that the diet caused a small but significant
      calcification not seen in the sibling groups with normal dietary Ca. Ca
      supplementation caused a significant 30% decrease in serum cholesterol (p <
      0.05). Calcium deficiency increased serum cholesterol by 57% (p < 0.001). Serum
      cholesterol and LDL-cholesterol levels in Ca deficient rabbits were 2-fold higher
      than those with high Ca diets. Ca supplementation decreased soluble Ca and Pi
      content in aortas, suggesting that this effect may underlie the effects of Ca
      supplementation on calcification. Calcium deficiency increased icterus by 33% (p
      < 0.05), which may affect hepatic clearance of cholesterol, while calcium
      supplementation decreased it by 43% (p < 0.001). CONCLUSION: Ca supplementation
      to an atherogenic diet inhibits atherosclerosis, aortic calcification, and
      icterus, whereas a Ca deficient-diet promotes them.

PMID- 16796747
TI  - Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential
      therapeutic target and prognostic marker.
AB  - BACKGROUND: To evaluate the expression and test the clinical significance of the
      epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell
      carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM
      directed targeted therapies. METHODS: The Ep-CAM expression was
      immunohistochemically investigated in 70 primary esophageal SCCs using the
      monoclonal antibody Ber-EP4. For the interpretation of the staining results, we
      used a standardized scoring system ranging from 0 to 3+. The survival analysis
      was calculated from 53 patients without distant metastasis, with R0 resection and
      at least 2 months of clinical follow-up. RESULTS: Ep-CAM neo-expression was
      observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%)
      and 3+ (41%). Heterogeneous expression was observed at all expression levels.
      Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly
      decreased median relapse-free survival period (log rank, p = 0.0001) and median
      overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed
      Ep-CAM 3+ expression as independent prognostic factor. CONCLUSION: Our results
      suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC.
      Considering the discontenting results of the current adjuvant concepts for
      esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant
      immunotherapeutic intervention.

PMID- 16796749
TI  - How much time do health services spend on antenatal care? Implications for the
      introduction of the focused antenatal care model in Tanzania.
AB  - BACKGROUND: Antenatal care (ANC) is a widely used strategy to improve the health
      of pregnant women and to encourage skilled care during childbirth. In 2002, the
      Ministry of Health of the United Republic of Tanzania developed a national
      adaptation plan based on the new model of the World Health Organisation (WHO). In
      this study we assess the time health workers currently spent on providing ANC
      services and compare it to the requirements anticipated for the new ANC model in
      order to identify the implications of Focused ANC on health care providers'
      workload. METHODS: Health workers in four dispensaries in Mtwara Urban District,
      Southern Tanzania, were observed while providing routine ANC. The time used for
      the overall activity as well as for the different, specific components of 71 ANC
      service provisions was measured in detail; 28 of these were first visits and 43
      revisits. Standard time requirements for the provision of focused ANC were
      assessed through simulated consultations based on the new guidelines. RESULTS:
      The average time health workers currently spend for providing ANC service to a
      first visit client was found to be 15 minutes; the provision of ANC according to
      the focused ANC model was assessed to be 46 minutes. For a revisiting client the
      difference between current practise and the anticipated standard of the new model
      was 27 minutes (9 vs. 36 min.). The major discrepancy between the two procedures
      was related to counselling. On average a first visit client was counselled for
      1:30 minutes, while counselling in revisiting clients did hardly take place at
      all. The simulation of focused ANC revealed that proper counselling would take
      about 15 minutes per visit. CONCLUSION: While the introduction of focused ANC has
      the potential to improve the health of pregnant women and to raise the number of
      births attended by skilled staff in Tanzania, it may need additional investment
      in human resources. The generally anticipated saving effect of the new model
      through the reduction of routine consultations may not materialise because the
      number of consultations is already low in Tanzania with a median of only 4 visits
      per pregnancy. Special attention needs to be given to counselling attitudes and
      skills during the training for Focused ANC as this component is identified as the
      major difference between old practise and the new model. Our estimated
      requirement of 46 minutes per first visit consultation matches well with the WHO
      estimate of 40 minutes.

PMID- 16796748
TI  - Differential prioritization between relevance and redundancy in correlation-based
      feature selection techniques for multiclass gene expression data.
AB  - BACKGROUND: Due to the large number of genes in a typical microarray dataset,
      feature selection looks set to play an important role in reducing noise and
      computational cost in gene expression-based tissue classification while improving
      accuracy at the same time. Surprisingly, this does not appear to be the case for
      all multiclass microarray datasets. The reason is that many feature selection
      techniques applied on microarray datasets are either rank-based and hence do not
      take into account correlations between genes, or are wrapper-based, which require
      high computational cost, and often yield difficult-to-reproduce results. In
      studies where correlations between genes are considered, attempts to establish
      the merit of the proposed techniques are hampered by evaluation procedures which
      are less than meticulous, resulting in overly optimistic estimates of accuracy.
      RESULTS: We present two realistically evaluated correlation-based feature
      selection techniques which incorporate, in addition to the two existing criteria
      involved in forming a predictor set (relevance and redundancy), a third criterion
      called the degree of differential prioritization (DDP). DDP functions as a
      parameter to strike the balance between relevance and redundancy, providing our
      techniques with the novel ability to differentially prioritize the optimization
      of relevance against redundancy (and vice versa). This ability proves useful in
      producing optimal classification accuracy while using reasonably small predictor
      set sizes for nine well-known multiclass microarray datasets. CONCLUSION: For
      multiclass microarray datasets, especially the GCM and NCI60 datasets, DDP
      enables our filter-based techniques to produce accuracies better than those
      reported in previous studies which employed similarly realistic evaluation
      procedures.

PMID- 16796750
TI  - TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer
      cells.
AB  - BACKGROUND: Activation of caspase-9 in response to treatment with cytotoxic drugs
      is inhibited in NSCLC cells, which may contribute to the clinical resistance to
      chemotherapy shown in this type of tumor. The aim of the present study was to
      investigate the mechanism of caspase-9 inhibition, with a focus on a possible
      role of TUCAN as caspase-9 inhibitor and a determinant of chemosensitivity in
      NSCLC cells. METHODS: Caspase-9 processing and activation were investigated by
      Western blot and by measuring the cleavage of the fluorogenic substrate LEHD-AFC.
      Proteins interaction assays, and RNA interference in combination with cell
      viability and apoptosis assays were used to investigate the involvement of TUCAN
      in inhibition of caspase-9 and chemosensitivity NSCLC. RESULTS: Analysis of the
      components of the caspase-9 activation pathway in a panel of NSCLC and SCLC cells
      revealed no intrinsic defects. In fact, exogenously added cytochrome c and dATP
      triggered procaspase-9 cleavage and activation in lung cancer cell lysates,
      suggesting the presence of an inhibitor. The reported inhibitor of caspase-9,
      TUCAN, was exclusively expressed in NSCLC cells. However, interactions between
      TUCAN and procaspase-9 could not be demonstrated by any of the assays used.
      Furthermore, RNA interference-mediated down-regulation of TUCAN did not restore
      cisplatin-induced caspase-9 activation or affect cisplatin sensitivity in NSCLC
      cells. CONCLUSION: These results indicate that procaspase-9 is functional and can
      undergo activation and full processing in lung cancer cell extracts in the
      presence of additional cytochrome c/dATP. However, the inhibitory protein TUCAN
      does not play a role in inhibition of procaspase-9 and in determining the
      sensitivity to cisplatin in NSCLC.

PMID- 16796751
TI  - Changes in Scottish suicide rates during the Second World War.
AB  - BACKGROUND: It is believed that total reported suicide rates tend to decrease
      during wartime. However, analysis of suicide rates during recent conflicts
      suggests a more complex picture, with increases in some age groups and changes in
      method choice. As few age and gender specific analyses of more distant conflicts
      have been conducted, it is not clear if these findings reflect a change in the
      epidemiology of suicide in wartime. Therefore, we examined suicide rates in
      Scotland before, during and after the Second World War to see if similar features
      were present. METHODS: Data on deaths in Scotland recorded as suicide during the
      period 1931-1952, and population estimates for each of these years, were obtained
      from the General Register Office for Scotland. Using computer spreadsheets,
      suicide rates by gender, age and method were calculated. Forward stepwise
      logistic regression was used to assess the effect of gender, war and year on
      suicide rates using SAS V8.2. RESULTS: The all-age suicide rate among both men
      and women declined during the period studied. However, when this long-term
      decline is taken into account, the likelihood of suicide during the Second World
      War was higher than during both the pre-War and post-War periods. Suicide rates
      among men aged 15-24 years rose during the Second World War, peaking at 148 per
      million (41 deaths) during 1942 before declining to 39 per million (10 deaths) by
      1945, while the rate among men aged 25-34 years reached 199 per million (43
      deaths) during 1943 before falling to 66 per million (23 deaths) by 1946. This
      was accompanied by an increase in male suicides attributable to firearms and
      explosives during the War years which decreased following its conclusion.
      CONCLUSION: All age male and female suicide rates decreased in Scotland during
      World War II. However, once the general background decrease in suicide rates over
      the whole period is accounted for, the likelihood of suicide among the entire
      Scottish population during the Second World War was elevated. The overall
      decrease in suicide rates concealed large increases in younger male age groups
      during the War years, and an increase in male suicides recorded as due to the use
      of firearms. We conclude that the effects of war on younger people, reported in
      recent conflicts in Central Europe, were also seen in Scotland during the Second
      World War. The results support the findings of studies of recent conflicts which
      have found a heterogeneous picture with respect to age specific suicide rates
      during wartime.

PMID- 16796752
TI  - Delay aversion but preference for large and rare rewards in two choice tasks:
      implications for the measurement of self-control parameters.
AB  - BACKGROUND: Impulsivity is defined as intolerance/aversion to waiting for reward.
      In intolerance-to-delay (ID) protocols, animals must choose between small/soon
      (SS) versus large/late (LL) rewards. In the probabilistic discount (PD)
      protocols, animals are faced with choice between small/sure (SS) versus
      large/luck-linked (LLL) rewards. It has been suggested that PD protocols also
      measure impulsivity, however, a clear dissociation has been reported between
      delay and probability discounting. RESULTS: Wistar adolescent rats (30- to 46-day
      old) were tested using either protocol in drug-free state. In the ID protocol,
      animals showed a marked shift from LL to SS reward when delay increased, and this
      despite adverse consequences on the total amount of food obtained. In the PD
      protocol, animals developed a stable preference for LLL reward, and maintained it
      even when SS and LLL options were predicted and demonstrated to become
      indifferent. We demonstrate a clear dissociation between these two protocols. In
      the ID task, the aversion to delay was anti-economical and reflected impulsivity.
      In the PD task, preference for large reward was maintained despite its uncertain
      delivery, suggesting a strong attraction for unitary rewards of great magnitude.
      CONCLUSION: Uncertain delivery generated no aversion, when compared to delays
      producing an equivalent level of large-reward rarefaction. The PD task is
      suggested not to reflect impulsive behavior, and to generate patterns of choice
      that rather resemble the features of gambling. In summary, present data do
      indicate the need to interpret choice behavior in ID and PD protocols
      differently.

PMID- 16796753
TI  - Development of a taxonomy to describe massage treatments for musculoskeletal
      pain.
AB  - BACKGROUND: One of the challenges in conducting research in the field of massage
      and bodywork is the lack of consistent terminology for describing the treatments
      given by massage therapists. The objective of this study was to develop a
      taxonomy to describe what massage therapists actually do when giving a massage to
      patients with musculoskeletal pain. METHODS: After conducting a review of the
      massage treatment literature for musculoskeletal pain, a list of candidate
      techniques was generated for possible inclusion in the taxonomy. This list was
      modified after discussions with a senior massage therapist educator and seven
      experienced massage therapists participating in a study of massage for neck pain.
      RESULTS: The taxonomy was conceptualized as a three level classification system,
      principal goals of treatment, styles, and techniques. Four categories described
      the principal goal of treatment (i.e., relaxation massage, clinical massage,
      movement re-education and energy work). Each principal goal of treatment could be
      met using a number of different styles, with each style consisting of a number of
      specific techniques. A total of 36 distinct techniques were identified and
      described, many of which could be included in multiple styles. CONCLUSION: A new
      classification system is presented whereby practitioners using different styles
      of massage can describe the techniques they employ using consistent terminology.
      This system could help facilitate standardized reporting of massage
      interventions.

PMID- 16796754
TI  - Bacterial genotyping by 16S rRNA mass cataloging.
AB  - BACKGROUND: It has recently been demonstrated that organism identifications can
      be recovered from mass spectra using various methods including base-specific
      fragmentation of nucleic acids. Because mass spectrometry is extremely rapid and
      widely available such techniques offer significant advantages in some
      applications. A key element in favor of mass spectrometric analysis of RNA
      fragmentation patterns is that a reference database for analysis of the results
      can be generated from sequence information. In contrast to hybridization
      approaches, the genetic affinity of any unknown isolate can in principle be
      determined within the context of all previously sequenced 16S rRNAs without prior
      knowledge of what the organism is. In contrast to the original RNase T1
      cataloging method, when digestion products are analyzed by mass spectrometry,
      products with the same base composition cannot be distinguished. Hence, it is
      possible that organisms that are not closely related (having different underlying
      sequences) might be falsely identified by mass spectral coincidence. We present a
      convenient spectral coincidence function for expressing the degree of similarity
      (or distance) between any two mass-spectra. Trees constructed using this function
      are consistent with those produced by direct comparison of primary sequences,
      demonstrating that the inherent degeneracy in mass spectrometric analysis of RNA
      fragments does not preclude correct organism identification. RESULTS: Neighbor
      joining trees for important bacterial pathogens were generated using distances
      based on mass spectrometric observables and the spectral coincidence function.
      These trees demonstrate that most pathogens will be readily distinguished using
      mass spectrometric analyses of RNA digestion products. A more detailed, genus
      level analysis of pathogens and near relatives was also performed, and it was
      found that assignments of genetic affinity were consistent with those obtained by
      direct sequence comparisons. Finally, typical values of the coincidence between
      organisms were also examined with regard to phylogenetic level and sequence
      variability. CONCLUSION: Cluster analysis based on comparison of mass
      spectrometric observables using the spectral coincidence function is an extremely
      useful tool for determining the genetic affinity of an unknown bacterium.
      Additionally, fragmentation patterns can determine within hours if an unknown
      isolate is potentially a known pathogen among thousands of possible organisms,
      and if so, which one.

PMID- 16796755
TI  - Prevalence and outcomes of delirium in community and non-acute care settings in
      people without dementia: a report from the Canadian Study of Health and Aging.
AB  - BACKGROUND: While delirium is common among older adults in acute care hospitals,
      its prevalence in other settings has been less well studied. We examined delirium
      prevalence and outcomes in a large cohort of older Canadians living outside of
      acute care. METHODS: In this secondary analysis of the Canadian Study of Health
      and Aging, the prevalence of clinically diagnosed delirium was estimated and five
      year survival was compared with that of individuals with dementia of graded
      severity. RESULTS: Delirium was very uncommon (prevalence <0.5%) and was
      associated with reduced survival, similar to that of moderate-to-severe dementia.
      CONCLUSION: In this cohort of older Canadians, delirium in non-demented people
      was associated with very low 5-year survival, at levels comparable with advanced
      dementia. Although it is common in hospital, delirium is uncommon among older
      adults in their usual place of residence, suggesting that it is a potent stimulus
      to seek medical care.

PMID- 16796756
TI  - Effect of high up front charges on access to surgery for poor patients at a
      public hospital in New Mexico.
AB  - BACKGROUND: A public hospital in New Mexico required collection of 50% of
      estimated costs prior to elective surgeries for self-pay patients. This study
      assesses the impact of this policy on access to elective surgical procedures.
      METHODS: Chi-square tests determined if there was a statistically significant
      difference between the number of self-pay and insured patient cancellations for
      financial reasons. A multivariate binomial regression model was used to calculate
      risk ratios and confidence limits for effects of race/ethnicity, and insurance
      status, controlling for gender, on these cancellations. RESULTS: Of the 667
      cancellations, there were 99 self-pay and 568 insured patients. Cancellations for
      financial reasons occurred in 55.6% of self-pay and 9.3% of insured patients (p <
      0.0001). Inability to pay 50% up front accounted for 76.4% of self-pay patient
      cancellations for financial reasons. Self-pay, non-Hispanic whites and minority
      race/ethnicities were 8.76 and 8.61 times more likely to cancel for financial
      reasons, respectively, than insured non-Hispanic whites. CONCLUSION: Self-pay
      patients, regardless of race/ethnicity, have elective surgical procedures
      cancelled for financial reasons significantly more often than insured patients.
      The hospital's 50% up-front payment policy represents a significant financial
      barrier to accessing elective surgical procedures for self-pay patients.

PMID- 16796758
TI  - The association of mammographic density with ductal carcinoma in situ of the
      breast: the Multiethnic Cohort.
AB  - INTRODUCTION: It is well established that women with high mammographic density
      are at greater risk for breast cancer than are women with low breast density.
      However, little research has been done on mammographic density and ductal
      carcinoma in situ (DCIS) of the breast, which is thought to be a precursor lesion
      to some invasive breast cancers. METHOD: We conducted a nested case-control study
      within the Multiethnic Cohort, and compared the mammographic densities of 482
      patients with invasive breast cancer and 119 with breast DCIS cases versus those
      of 667 cancer-free control subjects. A reader blinded to disease status performed
      computer-assisted density assessment. For women with more than one mammogram,
      mean density values were computed. Polytomous logistic regression models were
      used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for
      two measurements of mammographic density: percentage density and dense area.
      RESULTS: Mammographic density was associated with invasive breast cancer and
      breast DCIS. For the highest category of percentage breast density (> or = 50%)
      as compared with the lowest (< 10%), the OR was 3.58 (95% CI 2.26-5.66) for
      invasive breast cancer and 2.86 (1.38-5.94) for breast DCIS. Similarly, for the
      highest category of dense area (> or = 45 cm2) as compared with the lowest (< 15
      cm2), the OR was 2.92 (95% CI 2.01-4.25) for invasive breast cancer and 2.59
      (1.39-4.82) for breast DCIS. Trend tests were significant for invasive breast
      cancer (P for trend < 0.0001) and breast DCIS (P for trend < 0.001) for both
      percentage density and dense area. CONCLUSION: The similar strength of
      association for mammographic density with breast DCIS and invasive breast cancer
      supports the hypothesis that both diseases may have a common etiology.

PMID- 16796759
TI  - Prevention of disease progression in a patient with a gastric cancer-re
      recurrence. Outcome after intravenous treatment with the novel antineoplastic
      agent taurolidine. Report of a case.
AB  - BACKGROUND: Taurolidine (TRD) is a novel agent with multimodal antineoplastic
      effects. We present the case of a tumor remission after intravenous
      administration of taurolidine in a patient with gastric cancer re-recurrence.
      CASE PRESENTATION: A 58 years old male patient suffering from a gastric
      adenocarcinoma was submitted to partial gastrectomy and partial liver resection
      (pT2, pN1, pM1L (liver segment 2), N0, V0). 24 months later a local recurrence
      was diagnosed and the patient was reoperated. Postoperatively the patient
      underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A
      subsequent CT-revealed a liver metastasis and a recurrence adjacent to the
      hepatic artery. After successful radiofrequency ablation of the liver metastasis
      the patient was intravenously treated with 2% taurolidine. The patient endured
      the therapy well and no toxicity was observed. CT-scans revealed a stable disease
      without a tumor progression or metastatic spread. After 39 cycles the patient was
      submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days
      later due to myocardial infarction. Postmortem histology of the esophageal
      jejunal anastomosis and liver revealed complete remission of the known
      metastasized gastric adenocarcinoma. CONCLUSION: The intravenous treatment with
      2% taurolidine led to a histological remission of the tumor growth without any
      toxicity for the patient.

PMID- 16796760
TI  - Effects of an interactive CD-program on 6 months readmission rate in patients
      with heart failure - a randomised, controlled trial [NCT00311194].
AB  - BACKGROUND: Disease-management programmes including patient education have
      promoted improvement in outcome for patients with heart failure. However, there
      is sparse evidence concerning which component is essential for success, and very
      little is known regarding the validity of methods or material used for the
      education. METHODS: Effects of standard information to heart failure patients
      given prior to discharge from hospital were compared with additional education by
      an interactive program on all-cause readmission or death within 6 months. As a
      secondary endpoint, patients' general knowledge of heart failure and its
      treatment was tested after 2 months. RESULTS: Two hundred and thirty patients
      were randomised to standard information (S) or additional CD-ROM education (E).
      In (S) 52 % reached the endpoint vs. 49 % in (E). This difference was not
      significant. Of those who completed the questionnaire (37 %), patients in (E)
      achieved better knowledge and a marginally better outcome. CONCLUSION: The lack
      of effect on the readmission rate could be due to an insufficient sample size but
      might also indicate that in pharmacologically well-treated patients there is
      little room for altering the course of the condition. As there was some
      indication that patients who knew more about their condition might fare better,
      the place for intensive education and support of heart failure patients has yet
      to be determined.

PMID- 16796761
TI  - Are the distributions of variations of circle of Willis different in different
      populations? - Results of an anatomical study and review of literature.
AB  - BACKGROUND: Previous studies have proposed correlation between variants of the
      cerebral arterial circle (also known as circle of Willis) and some
      cerebrovascular diseases. Differences in the incidence of these diseases in
      different populations have also been investigated. The study of variations in the
      anatomy of the cerebral arterial circle may partially explain differences in the
      incidence of some of the cerebrovascular diseases in different ethnic or racial
      groups. While many studies have investigated the variations in the anatomy of
      each segment of the cerebral arterial circle, few have addressed the variants of
      the cerebral arterial circle as a whole. Similarly, the frequency of occurrence
      of such variants in different ethnic or racial groups has not been compared.
      METHODS: 102 brains of recently deceased Iranian males were dissected, in order
      to observe variations in the anatomy of the cerebral arterial circle. The
      dissection process was recorded on film and digitized. One resized picture from
      each dissection, showing complete circle has been made available online. The
      variations of the circle as whole and segmental variations were compared with
      previous studies. RESULTS: On the whole, the frequencies of the different
      variants of the entire cerebral arterial circle and segmental variations were
      comparable with previous studies.More specifically variants with uni- and
      bilateral hypoplasia of posterior communicating arteries were the most common in
      our study, similar to the previous works. No hypoplasia of the precommunicating
      part of the left anterior cerebral artery (A1), aplasia of A1 or the
      precommunicating part of the posterior cerebral artery (P1) was seen. In 3% both
      right and left posterior communcating arteries were absent. CONCLUSION: The
      anatomical variations found in the cerebral arterial circle of the Iranian males
      in the current study were not significantly different to those of more diverse
      populations reported in the literature. While taking into account potential
      confounding factors, the authors conclude that based on available studies, there
      is no evidence suggesting that the distributions of the variations of cerebral
      arterial circle differ in different populations.

PMID- 16796762
TI  - Circular instead of hierarchical: methodological principles for the evaluation of
      complex interventions.
AB  - BACKGROUND: The reasoning behind evaluating medical interventions is that a
      hierarchy of methods exists which successively produce improved and therefore
      more rigorous evidence based medicine upon which to make clinical decisions. At
      the foundation of this hierarchy are case studies, retrospective and prospective
      case series, followed by cohort studies with historical and concomitant non
      randomized controls. Open-label randomized controlled studies (RCTs), and finally
      blinded, placebo-controlled RCTs, which offer most internal validity are
      considered the most reliable evidence. Rigorous RCTs remove bias. Evidence from
      RCTs forms the basis of meta-analyses and systematic reviews. This hierarchy,
      founded on a pharmacological model of therapy, is generalized to other
      interventions which may be complex and non-pharmacological (healing, acupuncture
      and surgery). DISCUSSION: The hierarchical model is valid for limited questions
      of efficacy, for instance for regulatory purposes and newly devised products and
      pharmacological preparations. It is inadequate for the evaluation of complex
      interventions such as physiotherapy, surgery and complementary and alternative
      medicine (CAM). This has to do with the essential tension between internal
      validity (rigor and the removal of bias) and external validity
      (generalizability). SUMMARY: Instead of an Evidence Hierarchy, we propose a
      Circular Model. This would imply a multiplicity of methods, using different
      designs, counterbalancing their individual strengths and weaknesses to arrive at
      pragmatic but equally rigorous evidence which would provide significant
      assistance in clinical and health systems innovation. Such evidence would better
      inform national health care technology assessment agencies and promote evidence
      based health reform.

PMID- 16796763
TI  - Real-Time PCR for detection of herpes simplex virus without nucleic acid
      extraction.
AB  - BACKGROUND: The speed and sensitivity of real-time polymerase chain reaction
      (PCR) have made it a popular method for the detection of microbiological agents
      in both research and clinical specimens. For the detection and genotyping of
      herpes simplex virus (HSV) in clinical specimens, real-time PCR has proven to be
      faster, more sensitive and safer than earlier methods which included isolation of
      the virus in cell culture followed by immunofluorescence microscopy. While PCR
      based assays for HSV detection posses clear advantages over these earlier
      techniques, certain aspects of the PCR method remain onerous. The process of
      extraction and purification of nucleic acid from clinical specimens prior to PCR
      is particularly cumbersome. Nucleic acid extraction is expensive, time-consuming
      and provides a step whereby specimens can become contaminated prior to their
      analysis. Herein, we investigate the necessity of nucleic acid extraction from
      swab-based clinical specimens for HSV detection by real-time PCR. We find that
      nucleic acid extraction is unnecessary for specific and sensitive detection of
      HSV in clinical specimens using real-time PCR. METHODS: Prospective (n = 36) and
      retrospective (n = 21) clinical specimens from various anatomical sites were
      analyzed for the presence of herpes simplex virus 1 or 2 by real-time PCR using
      the RealArt HSV 1/2 LC PCR Kit. Specimens were analyzed by PCR both before and
      following automated nucleic acid extraction. PCR using extracted and unextracted
      specimens was also compared to cell culture as a means of detecting HSV. RESULTS:
      Detection of HSV 1/2 DNA in clinical specimens by real-time PCR did not require
      that the specimen be subjected to nucleic acid extraction/purification prior to
      analysis. Each specimen that was detectable by real-time PCR when analyzed in the
      extracted form was also detectable when analyzed in the unextracted form using
      the methods herein. The limit of detection of HSV-1 and HSV-2 particles when
      analyzed in the unextracted form was found to be approximately 17 and 32 virus
      particles respectively, compared to a sensitivity of 10 copies, for analysis of
      purified DNA. Omission of the nucleic acid extraction step shortened both the
      assay time and cost. CONCLUSION: Omission of the nucleic acid extraction step
      prior to real-time PCR for detection of herpes simplex virus resulted in a more
      rapid and cost-effective assay, with little impact upon the sensitivity of
      detection.

PMID- 16796764
TI  - Prediction of solubility on recombinant expression of Plasmodium falciparum
      erythrocyte membrane protein 1 domains in Escherichia coli.
AB  - BACKGROUND: Cellular interactions elicited by Plasmodium falciparum erythrocyte
      membrane protein antigen 1 (PfEMP1) are brought about by multiple DBL (Duffy
      binding like), CIDR (cysteine-rich interdomain region) and C2 domain types.
      Elucidation of the functional and structural characteristics of these domains is
      contingent on the abundant availability of recombinant protein in a soluble form.
      A priori prediction of PfEMP1 domains of the 3D7 genome strain, most likely to be
      expressed in the soluble form in Escherichia coli was computed and proven
      experimentally. METHODS: A computational analysis correlating sequence-dependent
      features to likelihood for expression in soluble form was computed and
      predictions were validated by the colony filtration blot method for rapid
      identification of soluble protein expression in E. coli. RESULTS: Solubility
      predictions for all constituent PfEMP1 domains in the decreasing order of their
      probability to be expressed in a soluble form (% mean solubility) are as follows:
      ATS (56.7%) > CIDR1alpha (46.8%) > CIDR2beta (42.9%) > DBL2-4gamma (31.7%) >
      DBL2beta + C2 (30.6%) > DBL1alpha (24.9%) > DBL2-7epsilon (23.1%) > DBL2-5delta
      (14.8%). The length of the domains does not correlate to their probability for
      successful expression in the soluble form. Immunoblot analysis probing for
      soluble protein confirmed the differential in solubility predictions. CONCLUSION:
      The acidic terminal segment (ATS) and CIDR alpha/beta domain types are suitable
      for recombinant expression in E. coli while all DBL subtypes (alpha, beta, gamma,
      delta, epsilon) are a poor choice for obtaining soluble protein on recombinant
      expression in E. coli. This study has relevance for researchers pursuing
      functional and structural studies on PfEMP1 domains.

PMID- 16796757
TI  - SPODOBASE: an EST database for the lepidopteran crop pest Spodoptera.
AB  - BACKGROUND: The Lepidoptera Spodoptera frugiperda is a pest which causes
      widespread economic damage on a variety of crop plants. It is also well known
      through its famous Sf9 cell line which is used for numerous heterologous protein
      productions. Species of the Spodoptera genus are used as model for pesticide
      resistance and to study virus host interactions. A genomic approach is now a
      critical step for further new developments in biology and pathology of these
      insects, and the results of ESTs sequencing efforts need to be structured into
      databases providing an integrated set of tools and informations. DESCRIPTION: The
      ESTs from five independent cDNA libraries, prepared from three different S.
      frugiperda tissues (hemocytes, midgut and fat body) and from the Sf9 cell line,
      are deposited in the database. These tissues were chosen because of their
      importance in biological processes such as immune response, development and
      plant/insect interaction. So far, the SPODOBASE contains 29,325 ESTs, which are
      cleaned and clustered into non-redundant sets (2294 clusters and 6103
      singletons). The SPODOBASE is constructed in such a way that other ESTs from S.
      frugiperda or other species may be added. User can retrieve information using
      text searches, pre-formatted queries, query assistant or blast searches.
      Annotation is provided against NCBI, UNIPROT or Bombyx mori ESTs databases, and
      with GO-Slim vocabulary. CONCLUSION: The SPODOBASE database provides integrated
      access to expressed sequence tags (EST) from the lepidopteran insect Spodoptera
      frugiperda. It is a publicly available structured database with insect pest
      sequences which will allow identification of a number of genes and comprehensive
      cloning of gene families of interest for scientific community. SPODOBASE is
      available from URL: http://bioweb.ensam.inra.fr/spodobase.

PMID- 16796765
TI  - Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the
      Cantonese population.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in
      southern China. In addition to environmental factors such as Epstein-Barr virus
      infection and diet, genetic susceptibility has been reported to play a key role
      in the development of this disease. The x-ray repair cross-complementing group 1
      (XRCC1) gene is important in DNA base excision repair. We hypothesized that two
      common single nucleotide polymorphisms of XRCC1 (codons 194 Arg-->Trp and 399 Arg
      ->Gln) are related to the risk of NPC and interact with tobacco smoking. METHODS:
      We sought to determine whether these genetic variants of the XRCC1 gene were
      associated with the risk of NPC among the Cantonese population in a hospital
      based case control study using polymerase chain reaction-restriction fragment
      length polymorphism analysis. We conducted this study in 462 NPC patients and 511
      healthy controls. RESULTS: After adjustment for sex and age, we found a reduced
      risk of developing NPC in individuals with the Trp194Trp genotype (OR = 0.48; 95%
      CI, 0.27-0.86) and the Arg194Trp genotype (OR = 0.79; 95% CI, 0.60-1.05) compared
      with those with the Arg194Arg genotype. Compared with those with the Arg399Arg
      genotype, the risk for NPC was not significantly different in individuals with
      the Arg399Gln genotype (OR = 0.82; 95% CI, 0.62-1.08) and the Gln399Gln genotype
      (OR = 1.20; 95% CI, 0.69-2.06). Further analyses stratified by gender and smoking
      status revealed a significantly reduced risk of NPC among males (OR = 0.32; 95%
      CI, 0.14-0.70) and smokers (OR = 0.34; 95% CI, 0.14-0.82) carrying the XRCC1
      194Trp/Trp genotype compared with those carrying the Arg/Arg genotype. No
      association was observed between Arg399Gln variant genotypes and the risk of NPC
      combined with smoking and gender. CONCLUSION: Our findings suggest that the XRCC1
      Trp194Trp variant genotype is associated with a reduced risk of developing NPC in
      Cantonese population, particularly in males and smokers. Larger studies are
      needed to confirm our findings and unravel the underlying mechanisms.

PMID- 16796767
TI  - Explicit information interferes with implicit motor learning of both continuous
      and discrete movement tasks after stroke.
AB  - A large portion of the rehabilitation experience after stroke relies on implicit
      learning. However, our understanding of how best to facilitate motor learning
      after stroke is limited by a paucity of research that has explored the
      interaction between explicit information and implicit learning across various
      task domains. Previously we reported that the delivery of explicit instructions
      disrupted implicit motor learning after stroke that involved the sensorimotor
      cortical areas or basal ganglia. The purpose of this study was to determine the
      robustness of these findings by determining whether they could be replicated with
      2 motor tasks, one discrete and one continuous, employed by the same group of
      participants. Ten individuals with stroke in the sensorimotor cortical areas
      (SMC), 10 with stroke in the basal ganglia (BG), and 10 age-matched healthy
      controls (HC) participated in this study. Each completed 3 days of practice of
      both a discrete implicit motor task (the serial reaction time task) and a
      continuous motor task (the continuous tracking task); all returned on a fourth
      day for retention tests. By random designation, participants were divided into
      either the explicit information (EI) or no explicit information (No-EI) groups.
      Consistent with previous results, we found that the response to explicit
      information after stroke was uniformly negative regardless of task or lesion
      location; both stroke groups demonstrated an interference effect of explicit
      information while the healthy control group did not. Strengthening these findings
      is the fact that the interference effect of explicit information was not task
      dependent. This point is particularly important for rehabilitation scientists as
      they instruct clients during various therapeutic tasks after stroke. Our data
      suggest that certain forms of explicit information delivered before task practice
      may not be as useful for learning as discovering the solution to the motor task
      with practice alone, and this is regardless of the type of task being learned.

PMID- 16796766
TI  - Genomic characterization of five deletions in the LDL receptor gene in Danish
      Familial Hypercholesterolemic subjects.
AB  - BACKGROUND: Familial Hypercholesterolemia is a common autosomal dominantly
      inherited disease that is most frequently caused by mutations in the gene
      encoding the receptor for low density lipoproteins (LDLR). Deletions and other
      major structural rearrangements of the LDLR gene account for approximately 5% of
      the mutations in many populations. METHODS: Five genomic deletions in the LDLR
      gene were characterized by amplification of mutated alleles and sequencing to
      identify genomic breakpoints. A diagnostic assay based on duplex PCR for the exon
      7-8 deletion was developed to discriminate between heterozygotes and normals, and
      bioinformatic analyses were used to identify interspersed repeats flanking the
      deletions. RESULTS: In one case 15 bp had been inserted at the site of the
      deleted DNA, and, in all five cases, Alu elements flanked the sites where
      deletions had occurred. An assay developed to discriminate the wildtype and the
      deletion allele in a simple duplex PCR detected three FH patients as
      heterozygotes, and two individuals with normal lipid values were detected as
      normal homozygotes. CONCLUSION: The identification of the breakpoints should make
      it possible to develop specific tests for these mutations, and the data provide
      further evidence for the role of Alu repeats in intragenic deletions.

PMID- 16796770
TI  - Predicting falls in individuals with Parkinson disease: a reconsideration of
      clinical balance measures.
AB  - BACKGROUND AND PURPOSE: Postural control problems, falls, and fall-related
      injuries are a common source of morbidity in elderly individuals, especially
      those with Parkinson disease (PD). Clinical balance tests such as the Berg
      balance scale and the functional reach have been reported to be useful in
      assessing fall risk in elderly individuals. However, the utility of commonly used
      clinical balance tests as accurate screens for fall risk has not been
      sufficiently examined in persons with PD. The purposes of this study were to
      identify which commonly used clinical balance tests of persons with PD were
      predictive of falls, to re-examine the cutoff scores for these tests with the
      goal of maximizing sensitivity as well as minimizing the negative likelihood
      ratio, and to determine which of the clinical balance tests had the most value in
      predicting falls. PARTICIPANTS: Forty-five persons with a diagnosis of idiopathic
      PD, aged 39-90 years (mean [sd] =69.94 [11.28]; mean [sd] Hoehn and Yahr level =
      2.60 [.66]) participated. METHODS: Upon initial contact with participants,
      demographics and fall history were gathered and baseline physical examinations
      were performed. Each individual underwent balance testing with the functional
      reach test, the Berg balance scale, the dynamic gait index, timed up and go, and
      the cognitive timed up and go. Fallers and nonfallers were divided based on fall
      history and groups were compared on balance test performance. Sensitivity,
      specificity, likelihood ratios, and receiver operator characteristic curves were
      calculated for all balance tests. RESULTS: Twenty-five (55%) participants had a
      history of falls. Using cut-off scores reported in previous studies, the
      sensitivity of all tests was low (less than 0.60) and the specificity was high
      (greater than 0.85). Reconsideration of the cut-off scores resulted in increased
      sensitivity for all tests (greater than 0.75) and low negative likelihood ratios
      (less then .30). DISCUSSION AND CONCLUSION: Given the large financial,
      psychological, and physical complications that are associated with a fall and
      relatively little harmful effects of fall prevention interventions, we propose
      consideration of cut-off scores that maximize sensitivity for individuals with
      PD. Regardless of the performance on any individual clinical balance test, the
      multifactorial nature of postural instability in PD may necessitate a battery of
      tests to provide the most accurate identification of fall risk.

PMID- 16796771
TI  - Cardiovascular response to treadmill testing in Parkinson disease.
AB  - PURPOSE: Exercise has been recommended as a way to maintain quality of life in
      individuals with Parkinson disease (PD). Experiments examining the cardiovascular
      response to exercise, however, have yielded controversial results. This study was
      designed to determine if there is any difference in vital signs and Rate of
      Perceived Exertion (RPE) between a group of individuals (50-80 years old) with PD
      and a comparison group of healthy individuals during exercise on a treadmill.
      METHODS: Twenty seven volunteers (16 with PD and 11 healthy) participated in this
      study. Subjects with PD were divided into 2 groups; one that reached target heart
      rate and one that failed to reach it. In this study, heart rate (HR), systolic
      blood pressure (BP), and the RPE were measured during a Modified Bruce Protocol.
      We hypothesized that treadmill testing would result in differences between
      individuals with PD and healthy subjects when HR and systolic BP were compared at
      submaximal exercise (defined as Stage 2 of the Modified Bruce Protocol) and at
      peak exercise (defined as 85% of age predicted target heart rate). RESULTS:
      During submaximal exercise, no significant differences were found between the PD
      group and the control group for HR, BP, or RPE. At peak exercise, one half of the
      subjects with PD exhibited blunted cardiovascular responses, despite reaching a
      comparable intensity of exercise during a Modified Bruce Protocol. CONCLUSIONS:
      Although cardiovascular responses to exercise on a treadmill appear similar
      between individuals with PD and controls at lower levels of exercise, half the
      subjects with PD in the present study displayed abnormal cardiovascular responses
      at higher exercise intensities. Administering an exercise stress test will
      illustrate the expected cardiovascular responses for each individual, therefore
      guiding exercise prescription.

PMID- 16796772
TI  - Reliability of clinical measures used to assess patients with peripheral
      vestibular disorders.
AB  - PURPOSE: The purposes of this research were to (1) determine test-retest
      reliability of clinical measures of self reported disability and subjective
      complaints, gait, and fall risk; and (2) establish normal variability for each of
      these measures based on test-retest variability in people with peripheral
      vestibular disorders. METHODS: Sixteen patients with confirmed peripheral
      vestibular disorders performed 2 trials of each of the measures within a single
      physical therapy session. The measures included rating of disability, percent of
      day affected by dizziness, head movement induced dizziness, preferred gait speed,
      gait deviations, and Dynamic Gait Index. In order to assess test-retest
      reliability of the measures intraclass correlation coefficients (ICC) were
      calculated. RESULTS: All measurement tools demonstrated excellent reliability
      (ICC 3,1 = 0.86 - 1.00) except for head movement induced dizziness (ICC 3,1 =
      0.48). For each measure we report normal variability as tested within a single
      session. DISCUSSION: Clinical measures commonly used in the assessment of
      vestibular patients were found to have excellent test-retest reliability, except
      for the subjective measure of head movement-induced dizziness. CONCLUSION:
      Incorporation of valid and reliable assessments in clinical practice is critical
      in order to demonstrate the effectiveness of therapeutic intervention.

PMID- 16796773
TI  - Outcomes of an aquatic exercise program including aerobic capacity, lactate
      threshold, and fatigue in two individuals with multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Fatigue in individuals with multiple sclerosis (MS) may
      be exacerbated by poor cardiovascular fitness. Although aqua aerobic exercise is
      often recommended, little research has been conducted on the efficacy of aqua
      aerobic exercise in improving cardiovascular fitness in patients with MS. The
      purpose of this case report is to describe changes in cardiovascular fitness and
      fatigue for 2 people with MS following an aqua aerobics class. CASE DESCRIPTIONS:
      The participants were 2 females, both with MS for over 10 years and mild
      disability. Participant A (40 years old and EDSS = 2.5/10) reported fatigue,
      numbness in her hands and feet, and occasional blurred vision. Participant B (51
      years old and EDSS = 3.0/10) reported the same problems as Participant A plus
      stiffness in her right lower extremity. The participants performed aqua aerobics
      at an intensity equivalent to their lactate threshold twice a week for 8 weeks.
      Lactate threshold is the exercise intensity just prior to the accumulation of
      blood lactate during graded exercise. OUTCOMES: A graded exercise test (with
      measurements of gas exchange) and a test of fatigue were administered before and
      after the intervention. Initially, both participants had poor cardiovascular
      fitness as demonstrated by their low peak oxygen consumption (VO2peak) and low
      lactate threshold (LT). After the intervention, both participants achieved a
      higher peak workload (their VO2peak increased) and they could sustain a higher
      submaximal workload without accumulation of acid substances causing fatigue
      (their LT increased). Changes in fatigue following the intervention were
      equivocal with Participant A reporting decreased fatigue and Participant B
      reporting no change. SUMMARY: This report describes the use of exercise testing
      to guide clinical decision making for dosing of an aqua aerobic fitness
      intervention and illustrates positive effects of the intervention on
      cardiovascular fitness in 2 people with MS.

PMID- 16796774
TI  - Meeting highlights from: 47th Annual Meeting of the American Society of
      Hematology December 2005, Atlanta, GA.

PMID- 16796775
TI  - Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with a 5-year
      survival rate of 35%-60%. Various clinical factors included in the International
      Prognostic Index have failed to identify the patients with DLBCL who will not
      benefit from the standard R-CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) treatment
      regimen. Bcl-2 has been implicated in conferring resistance to chemotherapy in
      non-Hodgkin's lymphoma and is therefore a candidate prognostic marker in DLBCL.
      To identify the correlation between Bcl-2 expression and response to rituximab
      containing treatment regimens, histologic materials were analyzed from 292
      elderly patients with confirmed DLBCL. Of these, 155 patients had received R-CHOP
      (53%) and 137 had received CHOP (47%). One hundred ninety-three patients (66%)
      were found to express high levels of Bcl-2 protein in > 50% of the tumor cells.
      Of the 193 Bcl-2-positive patients, the patients who received R-CHOP had a better
      5-year overall rate than patients treated with CHOP (56% vs. 42%; P = 0.01),
      whereas in the patients with Bcl-2-negative disease, there was no statistically
      significant difference in the 5-year overall survival rates between the R-CHOP
      and CHOP regimens (58% vs. 52%; P = 0.6). Therefore, the addition of rituximab to
      the standard chemotherapy regimen seems to have overcome the Bcl-2-associated
      resistance to chemotherapy.

PMID- 16796776
TI  - German Hodgkin's Lymphoma Study Group trials: lessons from the past and current
      strategies.
AB  - Over the past decades, Hodgkin's lymphoma has become one of the most curable
      tumors in adults. This is mainly because of large clinical trials using risk
      adapted, highly effective therapy modalities. For a long time, radiation therapy
      was the standard for treating patients with Hodgkin's lymphoma. Within the past
      20 years, management has undergone a paradigm shift from the use of chemotherapy
      as an adjunct to radiation therapy in advanced-stage disease to combined therapy
      modalities with chemotherapy and involved-field irradiation in early stages and
      time- and dose-intensified effective drug regimens in advanced stages. Modern
      therapeutic strategies aim at reducing therapy-associated acute and late
      toxicities, while maintaining the highest tumor control. Founded in 1978, the
      German Hodgkin's Lymphoma Study Group has initiated numerous clinical trials
      contributing to the high cure rate in all stages of this lymphoma entity. This
      article gives an overview of the German Hodgkin's Lymphoma Study Group trials and
      a review of the current treatment strategies.

PMID- 16796777
TI  - Superior 12-year survival after at least 4-year continuous remission with tandem
      transplantations for multiple myeloma.
AB  - BACKGROUND: Complete response has been considered a surrogate for favorable long
      term outcome in multiple myeloma. Data on the impact of the duration of response
      on prognosis are lacking. PATIENTS AND METHODS: Of the 899 patients enrolled in
      Total Therapy trials (Total Therapy 1, N = 231; Total Therapy 2, N = 668), 254
      survived for > 5 years. The prognostic impact of continuous (Rc) versus
      discontinuous (Rd) 4-year remission after 5-year survival was examined along with
      laboratory features present at baseline and at 5 years. RESULTS: Most baseline
      prognostic features were evenly distributed among Rc and Rd groups; however, a
      greater proportion of Rc patients were enrolled in Total Therapy 2 (60%) compared
      with Rd (19%; P < 0.001). Twelve-year survival (7 years after the 5-year
      landmark) was 66% with Rc and only 30% with Rd. Hypodiploidy and deletion 13,
      present in 24 patients at baseline, were associated with a 12-year survival of
      only 20%. Among the 200 patients lacking these cytogenetic abnormalities, Rc (n =
      141) defined a superior 12-year survival rate of 70% versus 35% among those with
      Rd (n = 59). Initial quality of response (complete response) or having received
      the scheduled tandem transplantations did not affect post-5-year survival.
      CONCLUSION: Five-year Rc appears to be an important prerequisite for prolonged
      subsequent overall survival.

PMID- 16796778
TI  - Intermediate-dose melphalan (100 mg/m2)/bortezomib/thalidomide/dexamethasone and
      stem cell support in patients with refractory or relapsed myeloma.
AB  - BACKGROUND: Bortezomib and thalidomide have shown synergy with melphalan and
      dexamethasone. We used this 4-drug combination as conditioning before autologous
      hematopoietic cell infusions. PATIENTS AND METHODS: Twenty-six patients with
      advanced-stage myeloma were treated with melphalan 50 mg/m(2) and bortezomib 1.3
      mg/m(2) on days -6 and -3 in association with thalidomide 200 mg and
      dexamethasone 20 mg on days -6 through -3, followed by hematopoietic cell support
      on day 0. RESULTS: Nonhematologic toxicities included pneumonia, febrile
      neutropenia, and peripheral neuropathy. All patients had undergone autologous
      transplantation at diagnosis, and 13 patients (50%) underwent an additional
      transplantation at relapse. Responses occurred in 17 of 26 patients (65%),
      including 1 complete remission, 3 near complete remissions (12%), and 2 very good
      partial remissions (8%). Response rate was higher than that induced by the
      previous line of treatment in 12 patients (46%). CONCLUSION:
      Melphalan/bortezomib/thalidomide/dexamethasone showed encouraging antimyeloma
      activity in patients with advanced-stage myeloma.

PMID- 16796779
TI  - CD52 is expressed on human mast cells and is a potential therapeutic target in
      Waldenstrom's Macroglobulinemia and mast cell disorders.
AB  - BACKGROUND: Alemtuzumab is a monoclonal antibody used in the treatment of CD52
      expressing B-cell malignancies, including Waldenstrom's macroglobulinemia (WM).
      Recent studies demonstrate high levels of alemtuzumab activity in
      relapsed/refractory disease. One potential target of alemtuzumab is bone marrow
      mast cells (BMMCs), which provide growth and survival signaling for WM
      lymphoplasmacytic cells. PATIENTS AND METHODS: We therefore examined BMMCs
      (FceRI+, CD117+) from WM and other mast cell (MC) disorders for expression of
      CD52. RESULTS: We identified cell surface antigen expression by multicolor flow
      cytometric analysis and found CD52 expressed on human mast-derived cell line-1
      (HMC-1) and LAD2 MC lines, on BMMC from 13 of 15 patients with WM, and on BMMCs
      from 4 of 4 patients with systemic mastocytosis (SM). None of 4 healthy donors
      expressed CD52. Reverse-transcriptase polymerase chain reaction analysis
      confirmed CD52 expression in the HMC-1 and LAD2 MC lines, in BMMCs from 14 of 15
      patients with WM, and 3 of 3 patients with SM. CD52 transcripts were also
      detected in BMMCs from 6 of 6 healthy donors, despite the absence of CD52 cell
      surface expression. Importantly, we observed high levels of alemtuzumab-mediated,
      antibody-dependent, cell-mediated cytotoxicity against LAD2 MCs and BMMCs from
      patients with WM and SM. CONCLUSION: These studies demonstrate that CD52 is
      widely expressed on human MCs and WM bone marrow lymphoplasmacytic cells and
      provide the preclinical rationale for the use of alemtuzumab in the treatment of
      WM and possibly other MC-related disorders.

PMID- 16796780
TI  - Late clinically silent perforation of intestinal non-Hodgkin's lymphoma.
AB  - The combined positron emission tomography/computed tomography scan is ideal in
      the initial staging of lymphomas and for evaluating the response to treatment. In
      posttreatment studies, the presence of a residual, metabolically active mass at
      the site of initially documented lymphoma is not expected to be anything other
      than residual active disease. We describe a case of intestinal non-Hodgkin's
      lymphoma that responded to chemotherapy but with a residual metabolically active
      mass at the site of initial disease. This mass was revealed to be a clinically
      silent closed intestinal perforation with abscess formation. Similar conditions
      should be kept in mind during the interpretation of posttreatment combined
      positron emission tomography/computed tomography scan and before exposing the
      patient to additional chemotherapy.

PMID- 16796782
TI  - Plasmablastic lymphoma presenting as an arm mass in an individual negative for
      human immunodeficiency virus: a case report.
AB  - Plasmablastic lymphoma is an aggressive diffuse large B-cell lymphoma classically
      arising in the oral cavities and jaws of individuals infected with the human
      immunodeficiency virus (HIV). More recently, cases of plasmablastic lymphoma have
      been identified in individuals negative for HIV. We report a case of
      plasmablastic lymphoma presenting as a rapidly expanding upper extremity mass in
      a 66-year-old individual negative for HIV. Aggressive multiple-agent chemotherapy
      resulted in a dramatic improvement of all symptoms. Increasing awareness of
      plasmablastic lymphoma in individuals who are HIV negative can allow for a better
      understanding of its clinical course and for specific chemotherapeutic regimens
      to be developed.

PMID- 16796781
TI  - Treatment of mycosis fungoides with denileukin diftitox and oral bexarotene.
AB  - Cutaneous T-cell lymphomas, including mycosis fungoides and Sezary syndrome, are
      often responsive to treatment, but current therapies have not been shown to
      increase survival, and in advanced stages, durable remissions are hard to
      achieve. We present a patient who was initially misdiagnosed with psoriasis and,
      16 years later, was diagnosed with mycosis fungoides. Denileukin diftitox was
      used as a tumor debulking agent to give a partial response that was further
      improved with a combination of systemic interferon/oral bexarotene and skin
      directed psorlen plus UV-A. The purpose of this case report is to show the value
      of sequential combination therapy for improving overall response.

PMID- 16796783
TI  - Activity of rituximab monotherapy in refractory splenic marginal zone lymphoma
      complicated with autoimmune hemolytic anemia.
AB  - We describe the case of a 61-year-old patient with refractory splenic marginal
      zone lymphoma and secondary autoimmune hemolytic anemia, both successfully
      treated with rituximab. This case demonstrates that rituximab monotherapy might
      also be a valid therapeutic approach in marginal zone lymphoma and autoimmune
      hemolytic anemia after failure of first-line treatment. Maintenance therapy,
      although expensive, could be useful to improve event-free survival in patients
      with unfavorable clinical behavior.

PMID- 16796784
TI  - 17-dimethylaminoethylamino-17-demethoxygeldanamycin in patients with advanced
      stage solid tumors and lymphoma: a phase I study.

PMID- 16796785
TI  - Panitumumab: a new anti-EGFR antibody for the treatment of advanced colorectal
      cancer.

PMID- 16796786
TI  - Highlights from: 97th annual meeting of the American Association for Cancer
      Research Washington, DC, April 2006.

PMID- 16796787
TI  - Clinical utility of gene microarray for the management of colorectal cancer.

PMID- 16796788
TI  - Randomized phase III trial results of panitumumab, a fully human anti-epidermal
      growth factor receptor monoclonal antibody, in metastatic colorectal cancer.
AB  - Monoclonal antibodies against the epidermal growth factor receptor have proven
      efficacy as monotherapy and in combination with chemotherapy in patients with
      metastatic colorectal cancer (CRC: mCRC). Initial clinical trials in CRC used the
      human-murine chimeric monoclonal antibody cetuximab. Ongoing studies are being
      conducted to evaluate the efficacy and safety of the fully human anti-epiderman
      growth factor receptor monoclonal antibody panitumumab. The results of a phase
      III trial which compared panitumumab as a single agent to best supportive care in
      patients with previously treated metastatic CRC have recently been reported
      Pantitumumab therapy resulted in a 46% reduction in the risk of tumor progression
      and a partial response rate of 8%. Rash was reported in 90% of patients with
      increased severity significantly correlated with improved medium overall survival
      (OS). Further clinical studies re ongoing and planned to test panitumumab in
      combination with chemotherapy in first-line therapy of advanced-stage CRC and
      adjuvant treatment of colon cancer.

PMID- 16796789
TI  - Impact of prognostic factors on clinical outcome after resection of colorectal
      pulmonary metastases.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in Western
      countries. Approximately 35% of patients will have metastatic disease at
      diagnosis, and an additional 25% of patients with resected stage II/III disease
      will develop recurrence. In approximately 30% of patients, metastatic disease
      will be restricted to a single organ, with the liver and lungs accounting for the
      majority of single organ-site metastases. In recent years, aggressive surgical
      resection of pulmonary metastases has become increasingly common with the
      recognition that this offers the best chance of long-term cure despite recent
      chemotherapeutic advances. Unfortunately, relapse after pulmonary resection
      remains approximately 70% despite advances in imaging and surgical technique.
      This review examines prognostic factors that influence survival after resection
      and repeat resection of pulmonary colorectal metastases and examines the impact
      of lymph node metastases, chemotherapy, and hepatic metastases on outcome.
      Pathologic markers that might determine outcome and current literature, which
      consists mainly of retrospective institutional reports, is reviewed.

PMID- 16796790
TI  - Does biomolecular characterization of stage II/III colorectal cancer have any
      prognostic value?
AB  - As new improvements in the treatment of colorectal cancer have become available,
      it has become important to understand the benefits of new therapies or the
      deleterious effects stemming from the increased risk of toxicity. In particular,
      a more rational approach to adjuvant chemotherapy for patients with stage II/III
      disease should be defined by understanding which patients have a higher
      recurrence risk. Many studies have investigated several molecular markers, but
      none has been definitively associated with patient outcome. We present a review
      of studies that have evaluated the immunohistochemical correlation between
      expression of some biomarkers, such as thymidylate synthase, p53, Ki-67, Bcl-2,
      and microsatellite instability status expressed by Mut-L homologue 1 and Mut-S
      homologue 2 proteins, and the prognosis of patients with stage II/III colorectal
      cancer. We have evaluated studies in which > or = 100 patients were involved in
      an effort to ensure a representative study group. The only biomarker likely to
      have a prognostic value is microsatellite instability status, which correlated
      with a better prognosis.

PMID- 16796791
TI  - Targeted agents for adjuvant therapy of colon cancer.
AB  - Among patients with colorectal cancer (CRC) diagnosed in the United States, 37.2%
      are diagnosed with stage III and 27.9% with stage II disease. In locoregionally
      advanced CRC, surgery is the primary treatment modality and has a curative
      intent. The survival depends on the pathologic stage and varies from 30%-60% for
      stage III to 60%-80% for stage II. However, as much as 40%-50% of patients will
      relapse and require additional treatment of the disease. Clinical failure after
      resection of CRC is predominantly secondary to the clinical progression of
      previously undetected distant metastatic disease. Until very recently, the
      absolute benefit for survival obtained with adjuvant therapy compared with
      control was about 6%. Introduction of oxaliplatin in the adjuvant setting has
      shown a reduction of 23% in the risk of relapse when compared with 5-fluorouracil
      alone (MOSAIC). Recent phase III studies have shown that targeted agents improved
      survival in patients with advanced-stage CRC. Bevacizumab, a monoclonal antibody
      targeting vascular endothelial growth factor, is the first antiangiogenic drug to
      show improved efficacy when used in combination with irinotecan and oxaliplatin
      for first- and second-line treatment of CRC. Cetuximab, another monoclonal
      antibody targeting epidermal growth factor receptor, has shown efficacy in third
      line therapy and promising results in first-line phase II studies. There is great
      interest in whether the biologic agents bevacizumab and cetuximab can improve
      survival in the adjuvant-therapy setting. This article reviews the adjuvant
      therapy for colon cancer and discusses the potential role and current trials
      involving the targeted agents.

PMID- 16796792
TI  - Estimating costs of care for patients with newly diagnosed metastatic colorectal
      cancer.
AB  - BACKGROUND: This study examines the resource use patterns and costs of care for
      patients with incident metastatic colorectal cancer (mCRC) based on analyses of
      retrospective claims data from selected health plans in the United States.
      PATIENTS AND METHODS: A case-control analysis was performed using claims from
      years 1998-2004. Incident mCRC cases were identified based on evidence of a
      colorectal cancer diagnosis and a metastatic disease diagnosis. Incident mCRC
      cases could have no other evidence of cancer in the 1-year period before the date
      of their first mCRC diagnosis. Cases were matched to non-mCRC controls based on
      age, sex, geographic region, and duration of plan enrollment. Costs were
      evaluated by phase of disease: diagnosis, treatment, or death phases. Ordinary
      least squares regressions were performed to evaluate impact of covariates in each
      phase. RESULTS: Total costs in the follow-up period averaged $97,031 more for
      mCRC cases than for controls. The main cost drivers for mCRC were
      hospitalizations ($37,369) and specialist visits ($34,582), which included
      chemotherapy administration. Approximately 40% of the 672 patients with mCRC who
      qualified for the phase analysis were identified with a fatal event during follow
      up. Monthly costs were similar in the diagnostic phase ($12,205) and death phase
      ($12,328), but were significantly lower in the treatment phase ($4722). Both
      mean/median monthly costs increased over time during the study period, regardless
      of disease phase. CONCLUSION: The economic burden of mCRC is substantial for
      patients with commercial health plans in the United States, and costs of care
      have increased substantially in recent years.

PMID- 16796793
TI  - Efficacy of cetuximab after treatment with oral epidermal growth factor receptor
      tyrosine kinase inhibitor-based chemotherapy in metastatic colorectal cancer.
AB  - PURPOSE: We studied the efficacy of cetuximab therapy in patients with metastatic
      colorectal cancer (mCRC) previously treated with an oral inhibitor of the
      tyrosine kinase domain of the epidermal growth factor receptor. PATIENTS AND
      METHODS: We reviewed the posttrial records of 73 patients with mCRC who
      participated in 1 of 3 clinical trials that examined a combination of gefitinib
      or erlotinib with standard cytotoxic chemotherapy. Medical and pharmacy records
      were used to identify patients who were subsequently treated with cetuximab-based
      therapy. Computed tomography scans during cetuximab-based therapy were reviewed,
      and the clinical activity of cetuximab was assessed by response rate using
      Response Evaluation Criteria in Solid Tumors and progression-free survival.
      RESULTS: Twenty-four patients with mCRC previously treated with gefitinib or
      erlotinib and combination cytotoxic chemotherapy who subsequently received
      cetuximab-based therapy were identified. While receiving cetuximab-based therapy,
      no patient experienced a partial or complete response; however, 3 patients (16%
      of patients with available scans for formal measurements) had a minor response,
      defined as a 15%-29.9% decrease in the sum of longest dimensions of target
      lesions, and 72% had stable disease. The progression-free survival was 5.1 months
      for all patients and 6 months for patients who had documented progression of
      disease while previously receiving gefitinib- or erlotinib-based therapy.
      CONCLUSION: Cetuximab appears to have clinical benefit in patients with mCRC
      previously treated with a chemotherapy regimen that included an oral tyrosine
      kinase inhibitor of epidermal growth factor receptor. Whether these results apply
      to other cancer types is unknown but worthy of further study.

PMID- 16796794
TI  - Long-term treatment with bevacizumab for patients with metastatic colorectal
      cancer: case report.
AB  - Bevacizumab is a monoclonal antibody to vascular endothelial growth factor that
      has demonstrated increased overall survival when added to standard chemotherapy
      regimens for metastatic colorectal cancer. Herein we report the cases of 2
      patients who demonstrated prolonged survival times of almost 5 and 6 years,
      respectively, on various chemotherapy regimens that also included bevacizumab.
      Throughout most of their disease course, these patients maintained a good quality
      of life, with some adjustments of chemotherapy doses because of side effects.
      Bevacizumab was generally well tolerated in long-term use.

PMID- 16796795
TI  - Capecitabine-induced cerebellar toxicity.
AB  - Capecitabine is an oral prodrug of 5-fluorouracil used in the treatment of
      adenocarcinoma of the colon. Neurotoxicity is an infrequently reported toxicity
      of capecitabine. We report a case of cerebellar ataxia secondary to capecitabine
      therapy.

PMID- 16796796
TI  - A pilot trial of a carcinoembryonic antigen/ TRICOM-based vaccine and radiation
      to liver metastases in patients with carcinoembryonic antigen-positive solid
      tumors.

PMID- 16796797
TI  - Cell secretion - finally sees the light.

PMID- 16796798
TI  - The story of cell secretion: events leading to the discovery of the 'porosome' -
      the universal secretory machinery in cells.
AB  - Cell secretion has come of age, and a century old quest has been elegantly
      solved. We have come a long way since earlier observations of what appeared to be
      'fibrillar regions' at the cell plasma membrane, and electrophysiological studies
      suggesting the presence of 'fusion pores' at the cell plasma membrane where
      secretion occurs. Finally, the fusion pore or 'porosome' has been discovered, and
      its morphology and dynamics determined at nm resolution and in real time in live
      secretory cells. The porosome has been isolated, its composition determined and
      it has been both structurally and functionally reconstituted in artificial lipid
      membrane. The discovery of the porosome as the universal secretory machinery in
      cells and the discovery of the molecular mechanism of vesicular content expulsion
      during cell secretion have finally enabled a clear understanding of this
      important cellular process. This review outlines the fascinating and exciting
      journey leading to the discovery of the porosome, ultimately solving one of the
      most difficult, significant, and fundamental cellular process -cell secretion.

PMID- 16796799
TI  - Interstitial cells of Cajal in the urethra.
AB  - The smooth muscle layer of the urethra generates spontaneous myogenic tone that
      is thought to make a major contribution to urinary continence. The mechanisms
      underlying generation of tone remain unclear, however recent studies from our
      laboratory highlighted a role for a specialised population of pacemaker cells
      which we originally referred to as interstitial cells (IC) and now term ICC.
      Urethra ICC possess an electrical pacemaker mechanism characterised by rhythmic
      activation of Ca(2+)-activated Cl(-) channels leading to spontaneous transient
      inward currents (STICs) under voltage clamp and spontaneous transient
      depolarisations (STDs) under current clamp conditions. Both STICS and STDs are
      now known to be associated with spontaneous Ca(2+) oscillations that result from
      a complex interplay between release of Ca(2+) from intracellular stores and
      Ca(2+) influx across the plasma membrane. In this review we will consider some of
      the precise mechanisms involved in the generation of pacemaker activity and
      discuss how these are modulated by excitatory and inhibitory neurotransmitters.

PMID- 16796800
TI  - Repair and regeneration: opportunities for carcinogenesis from tissue stem cells.
AB  - This review will discuss the mechanisms of repair and regeneration in various
      tissue types and how dysregulation of these mechanisms may lead to cancer. Normal
      tissue homeostasis involves a careful balance between cell loss and cell renewal.
      Stem and progenitor cells perform these biologic processes as the functional
      units of regeneration during both tissue homeostasis and repair. The concept of
      tissue stem cells capable of giving rise to all differentiated cells within a
      given tissue led to the concept of a cellular hierarchy in tissues and in tumors.
      Thus, only a few cells may be necessary and sufficient for tissue repair or tumor
      regeneration. This is known as the hierarchical model of tumorigenesis. This
      report will compare this model with the stochastic model of tumorigenesis. Under
      normal circumstances, the processes of tissue regeneration or homeostasis are
      tightly regulated by several morphogen pathways to prevent excessive or
      inappropriate cell growth. This review presents the recent evidence that
      dysregulation of these processes may provide opportunities for carcinogenesis for
      the long-lived, highly proliferative tissue stem cell population. New findings of
      cancer initiating tissue stem cells identified in several solid and circulating
      cancers including breast, brain and hematopoietic tumors will also be reviewed.
      Finally, this report reviews the cellular biology of cancer and its relevance to
      the development of more effective cancer treatment protocols.

PMID- 16796801
TI  - Tissue engineered nerve constructs: where do we stand?
AB  - Driven by enormous clinical need, interest in peripheral nerve regeneration has
      become a prime focus of research and area of growth within the field of tissue
      engineering. While using autologous donor nerves for bridging peripheral defects
      remains today's gold standard, it remains associated with high donor site
      morbidity and lack of full recovery. This dictates research towards the
      development of biomimetic constructs as alternatives. Based on current concepts,
      this review summarizes various approaches including different extracellular
      matrices, scaffolds, and growth factors that have been shown to promote migration
      and proliferation of Schwann cells. Since neither of these concepts in isolation
      is enough, although each is gaining increased interest to promote nerve
      regeneration, various combinations will need to be identified to strike a
      harmonious balance. Additional factors that must be incorporated into tissue
      engineered nerve constructs are also unknown and warrant further research
      efforts. It seems that future directions may allow us to determine the "missing
      link".

PMID- 16796802
TI  - Clinical and therapeutical implications of EPC biology in atherosclerosis.
AB  - Bone marrow-derived circulating endothelial progenitor cells have been
      successfully used to enhance angiogenesis after tissue ischemia. The role of
      endothelial progenitor cells in endothelial cell homeostasis and their putative
      role in atherogenesis have been recently investigated. Cardiovascular risk
      factors negatively influence endothelial progenitor cell number and function
      while vasculoprotection e.g. by statins, estrogens and physical activity may be
      partly mediated by progenitor cells. Endogenous mobilization or injection of ex
      vivo generated endothelial progenitor cells is associated with an enhanced
      reendothelialization, an improvement of endothelial function and reduced
      atherosclerotic burden. In contrast, endothelial progenitor cells may promote
      plaque angiogenesis in animal models and may negatively influence plaque
      development and stability. However, in humans with coronary atherosclerotic
      disease, endothelial progenitor cells are a novel risk predictor for
      cardiovascular mortality and morbidity. In this review we focus on the role of
      circulating endothelial progenitor cells in endothelial cell repair mechanisms at
      the vascular wall and their potentially protective and therapeutic role in
      atherosclerotic disease.

PMID- 16796804
TI  - The Prohibitins: emerging roles in diverse functions.
AB  - The prohibitins, Phb1 and Phb2 are highly conserved proteins in eukaryotic cells
      that are present in multiple cellular compartments. Initial investigations
      focused on the role of Phb1 as an inhibitor of cell proliferation hence the
      original name prohibitin. However both proteins appear to have a diverse range of
      functions and recent evidence suggests that the prohibitins have very similar but
      as yet only partially understood functions. In addition to their role as
      chaperone proteins in the mitochondria, and their ability to target to lipid
      rafts, their is now compelling evidence that both prohibitins are localized in
      the nucleus and can modulate transcriptional activity by interacting with various
      transcription factors, including the steroid hormone receptors, either directly
      or indirectly. In addition Phb1 and Phb2 are present in the circulation and can
      be internalized when added to cultured cells suggesting that the circulating
      prohibitins may have some regulatory role. This review presents some of the
      recent developments in prohibitin research and focuses on the similarities in the
      structure and function of these interesting proteins.

PMID- 16796803
TI  - Controlled and localized genetic manipulation in the brain.
AB  - Brain structure and function are determined in part through experience and in
      part through our inherited genes. A powerful approach for unravelling the balance
      between activity-dependent neuronal plasticity and genetic programs is to
      directly manipulate the genome. Such molecular genetic studies have been greatly
      aided by the remarkable progress of large-scale genome sequencing efforts.
      Sophisticated mouse genetic manipulations allow targeted point-mutations,
      deletions and additions to the mouse genome. These can be regulated through
      inducible promoters expressing in genetically specified neuronal cell types.
      However, despite significant progress it remains difficult to target specific
      brain regions through transgenesis alone. Recent work suggests that transduction
      vectors, like lentiviruses and adeno-associated viruses, may provide suitable
      additional tools for localized and controlled genetic manipulation. Furthermore,
      studies with such vectors may aid the development of human genetic therapies for
      brain diseases.

PMID- 16796805
TI  - Role of exosomes in immune regulation.
AB  - Exosomes are small vesicles originating from late endosomes, 30-100 nm in
      diameter with typical cup-shape morphology. They are reported to bear high levels
      of a narrow spectrum of molecules involved in immune response and signal
      transduction. Apart from removing obsolete membrane proteins, some surprising
      biological functions of exosomes were unveiled recently and their applications in
      immunotherapy of tumors are currently intensively investigated. Dendritic cell-
      (DC) and tumor-derived exosomes have considerable anti-tumor effects in
      experimental studies and several clinical trials. Despite their potential
      applications in eliciting a "positive" immune response, exosomes might induce
      some "unwanted" immune responses, such as immune tolerance and immune evasion.
      Therefore further investigations about the physiological functions of exosomes
      and the optimal way of exosome application in tumor immunotherapy are necessary.
      This review presents recent developments in the field of exosome research and
      focuses on its applications to tumor immunotherapy.

PMID- 16796806
TI  - Prospects for exosomes in immunotherapy of cancer.
AB  - Exosomes are nanometer sized membrane vesicles invaginating from multivesicular
      bodies and secreted from epithelial and hematopoietic cells. They were first
      described "in vitro" but vesicles with the hallmarks of exosomes are present in
      vivo in germinal centers and biological fluids. Their protein and lipid
      composition are unique and could account for their expanding functions such as
      eradication of obsolete proteins, antigen presentation or "Trojan horses" for
      viruses or prions. Exosome secretion could be a regulated process participating
      in the transfer of molecules inbetween immune cells. Despite numerous questions
      pertaining to their biological relevance, the potential of dendritic cell derived
      exosomes as cell-free cancer vaccines is currently being assessed. This review
      will summarize the composition and formation of exosomes, preclinical data, Phase
      I trials and optimization protocols for improving their immunogenicity in tumor
      bearing patients.

PMID- 16796807
TI  - Protein carbonylation, cellular dysfunction, and disease progression.
AB  - Carbonylation of proteins is an irreversible oxidative damage, often leading to a
      loss of protein function, which is considered a widespread indicator of severe
      oxidative damage and disease-derived protein dysfunction. Whereas moderately
      carbonylated proteins are degraded by the proteasomal system, heavily
      carbonylated proteins tend to form high-molecular-weight aggregates that are
      resistant to degradation and accumulate as damaged or unfolded proteins. Such
      aggregates of carbonylated proteins can inhibit proteasome activity. Alarge
      number of neurodegenerative diseases are directly associated with the
      accumulation of proteolysis-resistant aggregates of carbonylated proteins in
      tissues. Identification of specific carbonylated protein(s) functionally impaired
      and development of selective carbonyl blockers should lead to the definitive
      assessment of the causative, correlative or consequential role of protein
      carbonylation in disease onset and/or progression, possibly providing new
      therapeutic approaches.

PMID- 16796809
TI  - Membrane fusion in cells: molecular machinery and mechanisms.
AB  - Membrane fusion is a sine qua non process for cell physiology. It is critical for
      membrane biogenesis, intracellular traffic, and cell secretion. Although
      investigated for over a century, only in the last 15 years, the molecular
      machinery and mechanism of membrane fusion has been deciphered. The membrane
      fusion event elicits essentially three actors on stage: anionic phospholipids -
      phosphatidylinositols, phosphatidyl serines, specific membrane proteins, and the
      calcium ions, all participating in a well orchestrated symphony. Three soluble N
      ethylmaleimide-sensitive factor (NSF)-attachment protein receptors (SNAREs) have
      been implicated in membrane fusion. Target membrane proteins, SNAP-25 and
      syntaxin (t- SNARE) and secretory vesicle-associated membrane protein (v-SNARE)
      or VAMPwere discovered in the 1990's and suggested to be the minimal fusion
      machinery. Subsequently, the molecular mechanism of SNARE-induced membrane fusion
      was discovered. It was demonstrated that when t-SNARE-associated lipid membrane
      is exposed to v-SNARE-associated vesicles in the presence of Ca(2+), the SNARE
      proteins interact in a circular array to form conducting channels, thus
      establishing continuity between the opposing bilayers. Further it was proved that
      SNAREs bring opposing bilayers close to within a distance of 2-3 Angstroms,
      allowing Ca(2+) to bridge them. The bridging of bilayers by Ca(2+) then leads to
      the expulsion of water between the bilayers at the contact site, allowing lipid
      mixing and membrane fusion. Calcium bridging of opposing bilayers leads to the
      release of water, both from the water shell of hydrated Ca(2+) ions, as well as
      the displacement of loosely coordinated water at the phosphate head groups in the
      lipid membrane. These discoveries provided for the first time, the molecular
      mechanism of SNARE-induced membrane fusion in cells. Some of the seminal
      discoveries are briefly discussed in this minireview.

PMID- 16796808
TI  - Vascular physiology of a Ca2+ mobilizing second messenger - cyclic ADP-ribose.
AB  - Cyclic ADP-ribose (cADPR) is a novel Ca(2+) mobilizing second messenger, which is
      capable of inducing Ca(2+) release from the sarcoplasmic reticulum (SR) via
      activation of ryanodine receptors (RyR) in vascular cells. This signaling
      nucleotide has also been reported to participate in generation or modulation of
      intracellular Ca(2+) sparks, Ca(2+) waves or oscillations, Ca(2+)- induced Ca(2+)
      release (CICR) and spontaneous transient outward currents (STOCs) in vascular
      smooth muscle cells (VSMCs). With respect to the role of cADPR-mediated signaling
      in mediation of vascular responses to different stimuli, there is accumulating
      evidence showing that cADPR is importantly involved in the Ca(2+) response of
      vascular endothelial cells (ECs) and VSMCs to various chemical factors such as
      vasoactive agonists acetylcholine, oxotremorine, endothelin, and physical stimuli
      such as stretch, electrical depolarization and sheer stress. This cADPR-RyR
      mediated Ca(2+) signaling is now recognized as a fundamental mechanism regulating
      vascular function. Here we reviewed the literature regarding this cADPR signaling
      pathway in vascular cells with a major focus on the production of cADPR and its
      physiological roles in the control of vascular tone and vasomotor response. We
      also summarized some publish results that unveil the underlying mechanisms
      mediating the actions of cADPR in vascular cells. Given the importance of Ca(2+)
      in the regulation of vascular function, the results summarized in this brief
      review will provide new insights into vascular physiology and circulatory
      regulation.

PMID- 16796810
TI  - Insights into the interstitium of ventricular myocardium: interstitial Cajal-like
      cells (ICLC).
AB  - We have previously described interstitial Cajal-like cells (ICLC) in human atrial
      myocardium. Several complementary approaches were used to verify the existence of
      ICLC in the interstitium of rat or human ventricular myocardium: primary cell
      cultures, vital stainings (e.g.: methylene blue), traditional stainings
      (including silver impregnation), phase contrast and non-conventional light
      microscopy (Epon-embedded semithin sections), transmission electron microscopy
      (TEM) (serial ultrathin sections), stereology, immunohistochemistry (IHC) and
      immunofluorescence (IF) with molecular probes. Cardiomyocytes occupy about 75% of
      rat ventricular myocardium volume. ICLC represent approximately 32% of the number
      of interstitial cells and the ratio cardiomyocytes/ICLC is about 70/1. In the
      interstitium, ICLC establish close contacts with nerve fibers, myocytes, blood
      capillaries and with immunoreactive cells (stromal synapses). ICLC show
      characteristic cytoplasmic processes, frequently two or three, which are very
      long (tens up to hundreds of microm), very thin (0.1-0.5 microm thick), with
      uneven caliber, having dilations, resulting in a moniliform aspect. Gap junctions
      between such processes can be found. Usually, the dilations are occupied by
      mitochondria (as revealed by Janus green B and MitoTracker Green FM) and elements
      of endoplasmic reticulum. Characteristically, some prolongations are flat, with a
      veil-like appearance, forming a labyrinthic system. ICLC display caveolae (about
      1 caveola/ 1 microm cell membrane length, or 2-4% of the relative cytoplasmic
      volume). Mitochondria and endoplasmic reticulum (rough and smooth) occupy 5-10%
      and 1-2% of cytoplasmic volume, respectively. IHC revealed positive staining for
      CD34, EGFR and vimentin and, only in a few cases for CD117. IHC was negative for:
      desmin, CD57, tau, chymase, tryptase and CD13. IF showed that ventricular ICLC
      expressed connexin 43. We may speculate that possible ICLC roles might be:
      intercellular signaling (neurons, myocytes, capillaries etc.) and/or
      chemomechanical sensors. For pathology, it seems attractive to think that ICLC
      might participate in the process of cardiac repair/remodeling, arrhythmogenesis
      and, eventually, sudden death.

PMID- 16796811
TI  - Adiponectin promotes endothelial cell differentiation from human peripheral CD14+
      monocytes in vitro.
AB  - Adiponectin was revealed to have anti-atherogenic and anti-inflammatory
      properties and has been recently found to stimulate angiogenesis in vivo and in
      vitro. However, the role of adiponectin in endothelial differentiation remains
      unclear. The objective of this study was to investigate whether adiponectin can
      promote peripheral CD14(+) monocytes differentiation into endothelial cells
      (ECs). Human peripheral blood CD14(+) monocytes were cultured with or without
      adiponectin (10 microg/ml) for 10 days. Adiponectin significantly promoted EC
      morphology formation from CD14(+) monocytes. By flow cytometery analysis, cells
      treated with adiponection substantially increased mean fluorescence intensity of
      vascular endothelial growth factor receptor-2 (VEGFR-2) and endothelial nitric
      oxide synthase (eNOS), two specific endothelial markers, by 49.2 % and 53.9 %,
      respectively, as compared to control cells. By real time PCR analysis, the mRNA
      level of eNOS in adiponectin-treated cells was also increased by 31.9 % of that
      of the control cells. However, the mRNA levels of calponin and SMMHC, two
      specific SMC markers, in adiponectin-treated cells were decreased by 81.1 % and
      79.7 % of that of the control cells, respectively. These data demonstrated that
      adiponectin could promote endothelial differentiation from peripheral blood
      CD14(+) monocytes by morphology change, upregulation of EC markers and
      downregulation of SMC markers. Adiponectin-promoted EC differentiation may
      contribute to vascular healing and angiogenesis.

PMID- 16796812
TI  - Losartan attenuates phospholipase C isozyme gene expression in hypertrophied
      hearts due to volume overload.
AB  - Because the left ventricular (LV) hypertrophy due to volume overload induced by
      arteriovenous (AV) shunt was associated with an increase in phospholipase C (PLC)
      isozyme mRNA levels, PLC is considered to be involved in the development of
      cardiac hypertrophy. Since the renin-angiotensin system (RAS) is activated in
      cardiac hypertrophy, the role of RAS in the stimulation of PLC isozyme gene
      expression in hypertrophied heart was investigated by inducing AV shunt in
      Sprague-Dawley rats. The animals were treated with or without losartan (20 mg/kg,
      daily) for 3 days as well as 1, 2 and 4 weeks, and atria, right ventricle (RV)
      and LV were used for analysis. The increased muscle mass as well as the mRNA
      levels for PLC beta1 and beta3 in atria and RV, unlike PLC beta3 gene expression
      in LV, at 3 days of AVshunt were attenuated by losartan. The increased gene
      expression for PLC beta1 at 2 weeks in atria, at 1 and 4 weeks in RV, and at 2
      and 4 weeks in LV was also depressed by losartan treatment. Likewise, the
      elevated mRNA levels for PLC beta3 in RV at 1 week and in LVat 4 weeks of cardiac
      hypertrophy were decreased by losartan. On the other hand, the increased levels
      of mRNA for PLC gamma1 in RV and LV at 2 and 4 weeks of inducing hypertrophy,
      unlike in atria at 4 weeks were not attenuated by losartan treatment. While the
      increased mRNA level for PLC delta1 in LV was reduced by losartan, gene
      expression for PLC delta1 was unaltered in atria and decreased in RV at 3 days of
      inducing AV shunt. These results suggest that changes in PLC isozyme gene
      expression were chamber specific and time-dependent upon inducing cardiac
      hypertrophy due to AV shunt. Furthermore, partial attenuation of the increased
      gene expression for some of the PLC isozymes and no effect of losartan on others
      indicate that both RAS dependent and independent mechanisms may be involved in
      hypertrophied hearts due to volume overload.

PMID- 16796813
TI  - Generation of a scaffold free cartilage-like implant from a small amount of
      starting material.
AB  - INTRODUCTION: An autologous cellular based treatment of a traumatic cartilage
      injury requires a procedure whereby a biopsy of healthy cartilage is removed from
      the patient and the cells isolated and expanded by monolayer passage. This
      increases the cell number to required levels but also leads to a de
      differentiation of the cells. We aim to produce a scaffold-free, de-novo implant
      from a biopsy of cartilage. METHODS: Bovine chondrocytes were isolated from a
      small biopsy and expanded. The chondrocytic phenotype of the monolayer expanded
      cells was recovered during a period of culture in alginate and the effect of
      factors such as IGF1, TFGbeta1 and dexamethasone was investigated. RESULTS:
      During the alginate culture period a pre-treatment with IGF1 and dexamethasone
      was shown to have little effect. IGF1 however increased the glycosaminoglycan/DNA
      (GAG/DNA) content on day 14 to 84.95+/-5 ng/ng compared with 37.3+/-1.8 ng/ng in
      the controls (P<0.001). 35S labeling demonstrated an increased GAG synthesis in
      the presence of IGF1 (P<0.001). IGF1 also induced a increase of DNA content
      1383+/-314 ng/bead compared to 512+/-19 ng/bead in the controls (P<0.001). The
      cells were released from the alginate and cultured in a silicon mould for a
      further 14 days to obtain a three dimensional implant. Releasing the cells from
      the alginate and casting in a mould produced an implant of defined shape which
      contained no foreign material. After 31 days of culture the implants contained
      152.4+/-13.14 ng/ng GAG/DNA and 42.93+/-10.23 ng/ng collagen II. DISCUSSION: We
      believe alginate released chondrocytes provide a real alternative to artificial
      scaffolds.

PMID- 16796814
TI  - Methylene blue inhibits angiogenesis in chick chorioallontoic membrane through a
      nitric oxide-independent mechanism.
AB  - Angiogenesis is the process of generating new blood vessels from preexisting
      vessels and is considered essential in many pathological conditions. The purpose
      of the present study was to evaluate the effect of methylene blue in chick
      chorioallantoic membrane angiogenesis model in vivo. In this well characterized
      model, methylene blue inhibited angiogenesis in a concentration-dependent manner.
      In addition, when methylene blue was combined with sodium nitroprusside, a
      spontaneous generator of nitric oxide, an inhibition of angiogenesis was evident
      which was comparable with that observed by the application of methylene blue
      alone. Sodium nitroprusside, alone, caused a significant inhibition in basal
      angiogenesis. These results provide evidence that methylene blue inhibits
      angiogenesis independently of nitric oxide pathway and suggest that methylene
      blue may be useful for treating angiogenesis-dependent human diseases.

PMID- 16796815
TI  - MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer:
      correlations with prognostic factors.
AB  - The goal of our study was to analyse the prognostic values for some matrix
      metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases
      (TIMPs) in breast cancer. We evaluated the activity and the expression levels of
      MMP-9, MMP-2, TIMP-1 and TIMP-2 in malignant versus benign fresh breast tumor
      extracts. For this purpose, gelatinzymography, immunoblotting and ELISA were used
      to analyse the activity and expression of MMPs and TIMPs. We found that MMP-9
      expression level and activity are increased in malignant tumors. In addition, MMP
      9/TIMP-1 and MMP-2/TIMP-2 ratio values obtained by us were significantly
      different in malignant tumors compared to benign tumors. We suggest that the
      abnormal MMP-9/TIMP-1 balance plays a role in the configuration of breast
      invasive carcinoma of no special type and also in tumor growth, while altered MMP
      2/TIMP-2 ratio value could be associated with lymph node invasion and used as a
      prognostic marker in correlation with Nottingham Prognostic Index. Finally, we
      showed that in malignant tumors high expression of estrogen receptors is
      associated with enhanced activity of MMP-2 and increased bcl- 2 levels, while
      high expression of progesterone receptors is correlated with low TIMP-1 protein
      levels.

PMID- 16796816
TI  - Substance P and Neurokinin 1 receptor - expression is affected in the ileum of
      mice with mutation in the W locus.
AB  - The tachykinin substance P (SP) acts on the gut muscle coat via its preferred
      receptor, neurokinin 1 (NK1r). In the mouse ileum, NK1r-immunoreactivity (NK1r
      IR) was detected in neurons, in the interstitial cells of Cajal at the deep
      muscular plexus (ICC-DMP) and the myoid cells of the villi. SP-IR was detected in
      neurons and varicose nerve fibers, which were especially numerous at the DMP and
      closely associated with the ICC-DMP. In mice with a mutation in the W locus (ckit
      mutant animals), innervation is suggested to be normal although few studies have
      actually tested this hypothesis. Indeed, studies demonstrating ICC-DMP integrity
      are lacking and whether SP- and NK1r-IR are normal in these animals has not been
      investigated. Our aim was to perform an immunohistochemical study on the ileum of
      a strain of heterozygous mice with a mutation in the W locus, the W(e/+) mice, to
      test this hypothesis. SP-IR nerve fibers were significantly more numerous than in
      wild type mice; NK1r-IR was clustered on the plasma membrane and also
      intracytoplasmatic in the neurons, but absent in the ICC-DMP. The richness in SP
      IR nerve fibers and the NK1r-IR distribution in the neurons, similar to that of
      activated cells, might be attempts to compensate for the SP preferred receptor
      absence at the ICC-DMP. In conclusion, SP content and NK1r expression are
      noticeably different in c-kit mutants with respect to wild type mice, and
      probably causing an anomalous tachykininergic control of intestinal motility.
      Physiological studies on Wmutant mice have to take into account that innervation
      in this animal model is affected by the c-kit mutation.

PMID- 16796817
TI  - Caveolar nanospaces in smooth muscle cells.
AB  - Caveolae, specialized membrane nanodomains, have a key role in signaling
      processes, including calcium handling in smooth muscle cells (SMC). We explored
      the three-dimensional (3D) architecture of peripheral cytoplasmic space at the
      nanoscale level and the close spatial relationships between caveolae,
      sarcoplasmic reticulum (SR), and mitochondria, as ultrastructural basis for
      excitation-contraction coupling system and, eventually, for excitation
      transcription coupling. About 150 electron micrographs of SMC showed that
      superficial SR and peripheral mitochondria are rigorously located along the
      caveolar domains of plasma membrane, alternating with plasmalemmal dense plaques.
      Electron micrographs made on serial ultrathin sections were digitized, then
      computer-assisted organellar profiles were traced on images, and automatic 3D
      reconstruction was obtained using the Reconstruct software. The reconstruction
      was made for 1 microm(3) in rat stomach (muscularis mucosa) and 10 microm(3) in
      rat urinary bladder (detrusor). Caveolae, peripheral SR, and mitochondria close
      appositions create coherent cytoplasmic nanoscale subdomains of about 15 nm
      distance. Apparently, 80% of caveolae establish close contacts with SR and about
      10% establish close contacts with mitochondria in both types of SMC. Thus, our
      results showed that caveolae and peripheral SR build Ca(2+) release units at
      which mitochondria often could play a part. The couplings caveolae-SR occupy
      4.19% of cellular volume in stomach and 3.10% in rat urinary bladder, while
      couplings caveolae-mitochondria occupy 3.66% and 3.17% respectively. We conclude
      that there are strategic caveolae-SR or caveolae-mitochondria contacts at the
      nanoscale level in the cortical cytoplasm of SMC, presumably responsible for
      vectorial control of free Ca(2+) cytoplasmic concentrations in definite
      nanospaces. This may account for selective activation of specific Ca(2+)
      signaling pathways.

PMID- 16796819
TI  - The Ottorino Rossi.

PMID- 16796818
TI  - Caveolae and calcium handling, a review and a hypothesis.
AB  - Caveolae are associated with molecules crucial for calcium handling. This review
      considers the roles of caveolae in calcium handling for smooth muscle and
      interstitial cells of Cajal (ICC). Structural studies showed that the plasma
      membrane calcium pump (PMCA), a sodium-calcium exchanger (NCX1), and a myogenic
      nNOS appear to be colocalized with caveolin 1, the main constituent of these
      caveolae. Voltage dependent calcium channels (VDCC) are associated but not co
      localized with caveolin 1, as are proteins of the peripheral sarcoplasmic
      reticulum (SR) such as calreticulin. Only the nNOS is absent from caveolin 1
      knockout animals. Functional studies in calcium free media suggest that a source
      of calcium in tonic smooth muscles exists, partly sequestered from extracellular
      EGTA. This source supported sustained contractions to carbachol using VDCC and
      dependent on activity of the SERCA pump. This source is postulated to be
      caveolae, near peripheral SR. New evidence, presented here, suggests that a
      similar source exists in phasic smooth muscle of the intestine and its ICC. These
      results suggest that caveolae and peripheral SR are a functional unit recycling
      calcium through VDCC and controlling its local concentration. Calcium handling
      molecules associated with caveolae in smooth muscle and ICC were identified and
      their possible functions also reviewed.

PMID- 16796820
TI  - Benjamin Franklin and the neurosciences.
AB  - Benjamin Franklin (1706-1790), who is better known in other fields, especially
      colonial politics and international diplomacy, was an early, major contributor to
      the neurosciences from the New World. Among his accomplishments are: experiments
      on medical electricity as a possible cure for the palsies and hysteria; the first
      descriptions of how electricity affecting the brain can cause a specific type of
      amnesia; supporting the idea that cranial shocks might provide a cure for
      melancholia; showing that the cures performed by the Mesmerists to remove
      obstructions, including nerve blockages, rest on gullibility and suggestion, and
      recognizing the dangers, including those to the nerves, posed by exposure to
      lead. Franklin?s neuroscience was firmly based on experiments, careful
      observations, and hard data ? and finding clinical relevance for new discoveries
      was always on his mind.

PMID- 16796821
TI  - CADASIL: a short review of the literature and a description of the first family
      from Greece.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited disease clinically characterized by
      migraine, subcortical ischemic events, dementia and mood disorders. We present a
      short review of the literature on the clinical presentation of patients with
      CADASIL and provide recommendations for the detection and diagnosis of similar
      cases. We also describe the clinical, radiological and genetic findings of two
      Greek patients with CADASIL, members of the same family.

PMID- 16796822
TI  - Traditional electrodiagnostic testing in lumbar disc herniation.
AB  - For many years, traditional electrodiagnosis has been the main methodology for
      studying the radiculopathies. However, the current literature lacks full
      validation studies. We studied a population of 51 subjects with disc hernia,
      comparing their surgical reports with data obtained by electrodiagnostic testing.
      At the same time, we studied a population of 18 healthy subjects in order to
      obtain normative data. The analysis of the data allowed us to identify the cut
      off point for positivity vs negativity of electrodiagnostic testing in the
      population of healthy subjects and to verify the association between
      electrodiagnostic variables (rheobase and chronaxie indices, and shortened
      strength-duration curves) and the surgical findings. The statistical analysis
      showed an optimal correspondence between the surgical report and the
      electrodiagnostic test. This methodology may be integrated with the other tests
      in the diagnostic phase and used in the monitoring of rehabilitative treatment.

PMID- 16796823
TI  - Vascular endothelial growth factor induces brain erythropoietin expression?
AB  - To investigate whether the formation of vascular endothelial growth factor (VEGF)
      influences erythropoietin (EPO) expression in physiological conditions, we
      injected into the left lateral cerebral ventricle of the Mongolian gerbil an
      adeno-associated virus (AAV) vector capable of expressing the 165-amino-acid
      isoform of VEGF (VEGF165). Twelve and 18 days after AAV vector injection, the
      experimental animals were sacrificed and expression of EPO was evaluated through
      immunohistochemical analysis of both the hippocampus and the frontal cortex. We
      observed that VEGF165 induces EPO expression in the hippocampal pyramidal layers
      and in the frontal cortex of the gerbil, particularly after the 18th day
      following treatment with the vector, which suggests that VEGF165 could act as a
      hypoxic-like signal for EPO production. This finding could help to clarify the
      functional role of EPO and the molecular mechanisms by which VEGF might mediate
      its effects in the brain.

PMID- 16796824
TI  - The Symbol Digit Modalities Test - Oral version: Italian normative data.
AB  - In neuropsychological practice, the availability of effective and reliable tests
      is crucial. The Symbol Digit Modalities Test (SDMT) is widely used because it is
      easy to administer, reliable and also evaluates information processing speed. We
      set out to obtain normative data (currently unavailable for the Italian
      population) for the oral version of this test. Both age and education influenced
      performance on the SDMT; therefore, correction scores were obtained on the basis
      of these factors. The cut-off for normality was 34.2. The availability of Italian
      normative data for the SDMT will allow wider application of this test in clinical
      practice.

PMID- 16796825
TI  - Autistic epileptiform regression.
AB  - Autistic regression is a well known condition that occurs in one third of
      children with pervasive developmental disorders, who, after normal development in
      the first year of life, undergo a global regression during the second year that
      encompasses language, social skills and play. In a portion of these subjects,
      epileptiform abnormalities are present with or without seizures, resembling, in
      some respects, other epileptiform regressions of language and behaviour such as
      Landau-Kleffner syndrome. In these cases, for a more accurate definition of the
      clinical entity, the term autistic epileptifom regression has been suggested. As
      in other epileptic syndromes with regression, the relationships between EEG
      abnormalities, language and behaviour, in autism, are still unclear. We describe
      two cases of autistic epileptiform regression selected from a larger group of
      children with autistic spectrum disorders, with the aim of discussing the
      clinical features of the condition, the therapeutic approach and the outcome.

PMID- 16796826
TI  - A single case report of recurrent surgery for chronic back pain and its
      implications concerning a diagnosis of Munchausen syndrome.
AB  - While undergoing treatment in the psychiatric department, A.C., a 40-year-old
      white male, who had arrived in the casualty department complaining of an
      uncontrollable anxiety attack and in a state of fluctuating consciousness, was
      found to be suffering from a psychopathological condition characterized by
      pathological lying, gambling, compulsive restlessness, a long clinical history of
      chronic back pain, with multiple invasive diagnostic investigations and repeated
      surgery for disc hernia with relative complications, culminating in the fitment
      of a fixed neurostimulator, a slow-discharge morphine pump and the patient being
      granted a full disability pension. The continual increases in the doses of
      morphine suggested a tendency towards drug addiction. After providing a brief
      overview of the historical background and current concepts relating to the
      relationship between factitious disorders, malingering and hysteria, the authors
      discuss the differential diagnosis of the case, suggesting a diagnosis of
      Munchausen syndrome (the hypothesis best supported by the clinical evidence).
      This diagnosis, although the subject of much academic debate, is, unfortunately,
      still not frequently encountered in the medical literature, with the result that
      even today it has a strong clinical, relational and social impact.

PMID- 16796827
TI  - [Catheter ablation of atrial fibrillation: current view of indication].

PMID- 16796828
TI  - [Non-nodication treatment of heart failure: current view of remedy].

PMID- 16796829
TI  - [Clinic of fulfil and clinic of test for hypertension].

PMID- 16796830
TI  - [The new direction for research of ant hypertensive treatment strategy].

PMID- 16796831
TI  - [Intensive anti-platelet treatment: a new viewpoint in reperfusion strategy for
      ST segment elevation myocardial infarction].

PMID- 16796832
TI  - [Short-term outcomes of triple antiplatelet therapy after percutaneous coronary
      intervention].
AB  - OBJECTIVE: To evaluate short-term efficacy and safety of triple antiplatelet
      regimen (cilostazol combined with clopidogrel and aspirin) in patients who
      underwent percutaneous coronary intervention (PCI). METHODS: From October 2001 to
      April 2005, a total of 3135 patients underwent PCI in the General Hospital of
      Shenyang Command, People's Liberation Army, of which 1103 were treated with
      cilostazol 100 mg twice a day for 6 months in addition to aspirin and clopidogrel
      for 3 - 12 months as triple antiplatelet therapy regimen (triple group) after
      PCI, and 2032 of which received aspirin and clopidogrel for 3 - 12 months as dual
      antiplatelet therapy regimen after PCI (control group). The data of the incidence
      rates of major adverse cardiac events (MACE), subacute in-stent thrombosis (SAT),
      and hemorrhage events within 30 days after PCI of the two groups were
      retrospectively analyzed. RESULTS: The baseline clinical characteristics were
      comparable between these two groups. However, the proportions of the patients
      receiving stent implantation, with multivessel coronary artery diseases, and
      receiving PCI for unprotected left main trunk diseases of the triple group
      (91.3%, 68.3%, and 7.1% respectively) were all significantly higher than those of
      the control group (89.1%, 63.3%, and 4.6%, P < 0.05, P < 0.01, and P < 0.01). The
      proportion of patients with chronic total occlusions who received PCI in the
      triple group was 10.8%, significantly lower than that of the control group
      (13.4%, P < 0.05). No death occurred during procedure in both groups. The 30 d
      mortality and the rate of MACE with 30 days after PCI of the triple group were
      0.4% and 1.3%, both significantly lower than those of the control group (1.6%,
      and 2.6%, both P < 0.05). However, there were no significant differences in the
      incidence rates of SAT and major hemorrhage events between these 2 groups (0.7%
      vs 1.0% and 0.3% vs. 0.2% respectively, both P > 0.05). CONCLUSION: This novel
      triple antiplatelet regimen (aspirin and clopidogrel combined with cilostazol)
      for PCI patients is safe and more efficient than the dual antiplatelet therapy
      regimen (clopidogrel and aspirin) in reducing mortality and incidence of MACE in
      a short-term period.

PMID- 16796833
TI  - [Profile of risk factors modification after coronary revascularization in
      patients with coronary artery disease].
AB  - OBJECTIVE: To elucidate the profile of risk factors modification after
      percutaneous coronary intervention (PCI) or coronary artery bypass grafting
      (CABG) in patients with coronary artery disease in order to scale the gap between
      real world practice and evidence-based guidelines. METHODS: 3767 patients with at
      least 30 days' followed-up after discharge in the single-center DESIRE (Drug
      Eluting Stent Impact on REvascularization) registry were enrolled to compare in
      hospital and follow-up data including smoking, body weight, blood pressure,
      fasting blood sugar and lipid levels. RESULTS: Of the 3763 patients, 3017 (80.2%)
      were successfully followed up for at least one month with a median of 670 (35 -
      1930) days. During follow-up, 18.5% (170/917) of the in-hospital current smokers
      continued smoking, whereas 6.1% (71/1168) of the non-current smokers during
      hospitalization became cigarette addict despite a marked reduction in the general
      rate of current smoking (43.5% vs 9.5%, P < 0.0001). At follow-up, 24.3%
      (264/1087) of the overweight or obese patients experienced weight gain after
      revascularization. In patients with diabetes mellitus, 48.3% (143/296) had higher
      follow-up levels of average fasting blood sugar. In patients complicated with
      hypertension, 33.1% (469/1419) and 31.9% (453/1419) had higher average systolic
      or diastolic pressures than in-hospital measurements. During follow-up, 36.4%
      (111/184) had lower levels of serum high-density lipoprotein cholesterol (HDL-C),
      whereas 54.1% (98/181) and 56.8% (121/213) patients had higher levels of serum
      low-density lipoprotein cholesterol (LDL-C) and triglycerlin (TG). CONCLUSION:
      Risk factors modification after coronary revascularization is far beyond optimal,
      with a high rate of continued smoking and poor control of body weight, blood
      sugar, blood pressure and serum lipids. Prompt and effective measures should be
      taken to enhance the secondary prevention and patient education to minimize the
      gap between clinical practice and evidence-based guidelines.

PMID- 16796834
TI  - [Visualization of intimal proliferation of drug-eluting stent and bare mental
      stent by use of optical coherence tomography].
AB  - OBJECTIVE: To compare neointimal proliferation of drug-eluting stent (DES) with
      bare mental stent (BMS) by optical coherence tomography (OCT). METHODS: OCT
      images were obtained in 21 diseased coronary vessels with 23 stents in 19
      patients with coronary artery disease at 5 - 93 months post DES or BMS stents.
      Twenty-two stents of all 23 stents were divided into three groups. Nine DES
      stents at 6 - 10 months post stenting were considered as group A, 8 BMS stents at
      5 - 10 months post stenting as group B, and 5 BMS stents at 23 - 93 months post
      stenting as group C. OCT images were quantitatively analyzed to compare
      neointimal proliferation of three groups after stenting. RESULTS: All 21 vessels
      and 23 stents OCT images were successfully acquired. The maximal neointima,
      luminal loss in diameter and cross sectional area (CSA), and restenosis in
      diameter and CSA were significantly statistically different within three groups.
      The maximal intimal proliferations post stenting in group A were significantly
      lower than group B (0.20 mm +/- 0.13 mm vs 0.81 mm +/- 0.46 mm, P = 0.019) or
      group C (0.91 mm +/- 0.27 mm, P = 0.007), luminal loss of diameter in group A
      were significantly lower than group B (0.27 mm +/- 0.17 mm vs 1.12 mm +/- 0.79
      mm, P = 0.009) or group C (1.20 mm +/- 0.31 mm, P = 0.013), restenosis rates in
      diameter in group A were significantly less than group B (8.90% +/- 4.47% vs
      36.36% +/- 24.34%, P = 0.009) or group C (35.48 +/- 6.09, P = 0.017), luminal
      loss in CSA in group A were lower than group B (1.14 mm(2) +/- 0.9 mm(2) vs 3.96
      mm(2) +/- 2.62 mm(2), P = 0.009) or group C (4.66 mm(2) +/- 1.66 mm(2), P =
      0.006), and restenosis rates in CSA in group A were less than group B (15.43% +/-
      7.89% vs 48.14% +/- 30.43%, P = 0.017) or group C (55.20% +/- 11.24%, P = 0.009).
      Almost all surfaces of 13 BMS stent struts were covered by significant neointimal
      coverage, surfaces of 10 DES struts were less significantly neointimal coverage,
      and some surfaces of DES struts were uncovered with neointima even at 29 months
      post stenting. CONCLUSION: OCT imaging can clearly visualize stent struts and
      neointimal formation of strut surfaces post DES or BMS stenting, and this new
      imaging modality will play important role in evaluating the efficacy of drug
      eluting stent.

PMID- 16796836
TI  - [Long term follow-up on emergent intracoronary autologous bone marrow mononuclear
      cell transplantation for acute inferior-wall myocardial infarction].
AB  - OBJECTIVE: To investigate the effects of emergent intracoronary autologous bone
      marrow mononuclear cell (BM-MNC) transplantation on left ventricular function and
      myocardium lesion area in patients with first acute inferior-wall myocardial
      infarction. METHODS: Forty patients with first onset of acute inferior-wall
      myocardial infarction, 28 males and 12 females, aged < or = 75, treated with
      emergent percutaneous coronary intervention (PCI) were randomly divided into 2
      equal groups: group undergoing intracoronary transplantation of autologous BM-MNC
      via a micro-catheter right after PCI (BM-MNC group), and control group receiving
      normal saline and heparin. Blood routine examination, myocardium zymogram, and
      serum high sensitive C reactive protein (hsCRP) were detected, and 24-hour
      dynamic electrocardiography, delayed-enhancement myocardial magnetic resonance
      imaging (CMR), and angiography of the coronary artery and left ventricle were
      conducted before the transplantation and immediately, 1 week, and 6 months after
      transplantation. RESULTS: CMR showed that 6 months later the left ventricular
      ejection fraction (LVEF) of the control group was 47.9% +/- 6.7%, significantly
      higher than that 1 week later (43.4% +/- 6.7%, P = 0.001), and the LVEF of the BM
      MNC group 6 months later was 51.5% +/- 5.2%, significantly higher than that 1
      week later (44.5% +/- 7.1%, P = 0.001; however, the absolute change of LVEF
      (DeltaLVEF) of the BM-MNC group was 6.95% +/- 3.33%, significantly higher than
      that of the control group (4.05% +/- 1.68%, P = 0.047). Six months later the
      myocardial lesion area of the BM-MNC group decreased more significantly in
      comparison with the control group. Nevertheless, there was no difference in
      change of left ventricular end diastolic volume (LVEDV) between these two groups.
      The serum hsCRP 48 h after transplantation of the BM-MNC group was 2.8 g/L +/-
      0.8 g/L, significantly lower than that before transplantation (13.4 g/L +/- 3.6
      g/L, P < 0.001). No severe clinical events, such death, recurrent cardiac
      infarction, malignant arrhythmia, occur in these 2 groups. CONCLUSION: Emergent
      intracoronary transplantation of autologous BM-MNC in patients with acute
      inferior-wall myocardial infarction improves the left ventricular function and
      myocardial infusion, minimizes the myocardial lesion area significantly.

PMID- 16796837
TI  - [Pulmonary vein antrum isolation guided by 3-D mapping system in 100 patients
      with chronic atrial fibrillation].
AB  - OBJECTIVE: To investigate the efficacy and safety of circumferential pulmonary
      vein (PV) linear ablation (CPVA) guided by 3-D mapping system in patients with
      chronic atrial fibrillation (CAF). METHODS: From August 2004 to November 2005,
      100 consecutive patients with CAF were admitted to undergo CPVA guided by CARTO
      system and EnSite NavX system, the main procedure end point is electrical
      isolation of PVs. Success was defined as atrial tachyarrhythmia free without any
      antiarrhythmia drugs for at least 3 months. Clinical and procedural variables
      were collected, ANOVA analysis was employed to identify the risk factors
      predicting recurrence, P < 0.05 was considered significant. RESULTS: After a mean
      of 9.7 +/- 5.7 months follow up, 70% (70/100) of patients freed from AF. ANOVA
      analysis identified isthmus ablation and poor left ventricular ejection fraction
      as the independent factors predicting success. Complications including
      pericardial tamponade (3 cases, 3%), stroke (1 case, 1%), asymptomatic pulmonary
      vein stenosis (2 cases, 2%). CONCLUSION: CPVA guided by 3-D mapping system can be
      performed in CAF patients with an acceptable efficacy, but safety need to be
      improved.

PMID- 16796838
TI  - [Endovascular stent-graft repair for penetrating atherosclerotic ulcer of the
      descending aorta].
AB  - OBJECTIVE: To summarize the clinical experience and effectiveness of endovascular
      stent-graft placement for the treatment of penetrating atherosclerotic ulcer of
      the descending thoracic aorta. METHODS: From August 2002 to February 2006, 14
      patients with penetrating atherosclerotic ulcer accepted endovascular stent
      grafts placement. All patients were men, their average age was 60 years. The
      clinical symptoms included thoracalgia or notalgia or celiodynia (n = 13) and
      hemoptysis (n = 3). 11 patients had hypertension. All patients were diagnosed by
      CT or MRI scans. Via the cutdown on a femoral artery at local anesthesia, the
      stent-graft was placed after completion angiography. Then DSA examine was
      repeated. X-ray and EBCT or MDCT scans were performed at follow-up. RESULTS: 16
      Stent-grafts were successfully placed in 14 patients, in which 2 cases were
      placed with two stent-grafts respectively. There were Talent stent-grafts (n =
      11) and Aegis stent-grafts (n = 5). The diameter of endovascular stent-graft
      ranged 32 mm to 38 mm exceeding by 10% - 20% of aortic diameter of anchoring
      zone. Instant angiography revealed no endoleak in 12 patients, minor endoleak in
      2 patients. Within the follow-up average 17.2 months, CT scans demonstrated the
      disappearances of penetrating atherosclerotic ulcer or exclusion of aortic
      pseudoaneurysm in all patients, and absorption of intramural hematoma in two
      patients. One patient died of rupture of aortic pseudoaneurysm after one month.
      CONCLUSION: Penetrating atherosclerotic ulcer can leads to intramural hematoma,
      dissection, aneurysmal dilatation, pseudoaneurysm, or aortic rupture. Therefore
      it should be treated once diagnosed. Endovascular stent-graft placement may be an
      effective treatment for penetrating atherosclerotic ulcer, especially in patients
      with poor condition.

PMID- 16796839
TI  - [Impact of calcified lesion on the intimal hyperplasia after implantation of drug
      eluting stent: an intravascular ultrasound study].
AB  - OBJECTIVE: To investigate the impact of calcified lesion on the intimal
      hyperplasia after implantation of drug eluting stent. METHODS: Ninety-nine
      rapamycin-eluting stents were implanted into the left anterior descending
      branches of coronary artery of 97 patients with 99 lesions. Eight months later
      intravascular ultrasound (IVUS) was used to examine the cross section area (CSA)
      of the external elastic membrane (EEM) at the stent inlet and at the stent
      outlet, in-stent CSA, CSA of the lumen, area of neo-intima (in-stent area minus
      lumen CSA), the maximum and minimum diameters of stent, and symmetry index of
      stent (minimal diameter of stent/maximum diameter of stent). RESULTS: Forty-one
      lesions were calcified and 58 non-calcified. Fourteen of the 99 lesions in the 97
      patients developed intimal hyperplasia. The inlet stent CSA of the calcified
      group was (7.30 +/- 1.94) mm(2), similar to that of the non-calcified group (6.58
      +/- 1.96) mm(2); the outlet CSA of the calcified group was (6.74 +/- 2.02) mm(2),
      similar to that of the non-calcified group (6.14 +/- 1.82) mm(2). The minimum
      stent CSA of the calcified group was (4.97 +/- 1.51) mm(2), significantly smaller
      than that of the non-calcified group (6.10 +/- 1.87) mm(2) (P < 0.05), the
      symmetry index of the calcified group was 0.92 +/- 0.07, significantly lower than
      that of the non-calcified group (0.92 +/- 0.07, P < 0.05), and the intimal area
      of the calcified group was (0.02 +/- 0.20) mm(2), significantly smaller than that
      of the non-calcified group (0.53 +/- 1.50) mm(2) (P < 0.05). CONCLUSION: Drug
      eluting stent implantation in the patients with calcified lesions has a less
      stent CSA and poor symmetry, and less intimal hyperplasia compared with those in
      the non-calcified lesions.

PMID- 16796840
TI  - [Protective effect of protein kinase C on heart function: an experiment with
      isolated rabbit hearts].
AB  - OBJECTIVE: To investigate the protective effect of protein kinase C on heart
      function. METHODS: The hearts of 40 rabbits were isolated, underwent Langendorff
      perfusion, and randomly divided into 4 equal groups: Group I (control group, the
      heart underwent long ischemia or preservation for I hour, was re-warmed and re
      infused, and then re-perfused with K-H fluid), Group II (ischemic preconditioning
      group, perfusion was stopped for 5 minutes before the long ischemia, then the
      aorta was re-infused), Group III (specific activator of PKC, phorbol myristate
      acetate was infused inversely via the aorta before the perfusion of K-H fluid),
      and Group IV (polymyxin B, a specific antagonist of PKC, was infused after the
      infusion of PKC). Before the preservation and by the end of reperfusion left
      ventricle end systolic pressure (LVESP), and left ventricle end diastolic
      pressure (LVDSP) were measured. At the end of experiment specimens of myocardium
      were collected from each heart to measure the water content, the levels of lactic
      dehydrogenase and MB isoenzyme of creatine kinase (CK-MB), superoxide dismutase
      (SOD), and malonyldialdehyde (MDA). TUNEL method was used to measure the number
      of apoptotic cardiomyocyte. RESULTS: All heart resumed beating. The LVESP of
      Group II and III were both significantly higher than those of Groups I and IV
      (all P < 0.05) and the LVESP of Group III was significantly higher than that of
      Group II too (P < 0.05). The LVEDP of Group II and III were both significantly
      lower than those of Groups I and IV (all P < 0.05) and the LVEDP of Group III was
      significantly lower than that of Group II too (P < 0.05). The levels of CK-MB,
      LDH, and SOD of Group II and III were all significantly higher than those of
      Groups I and IV (all P < 0.05) and the levels of CK-MB and LDH of Group III was
      significantly higher than that of Group II too (P < 0.05). The level of MDA of
      Group II and III were both significantly lower than those of Groups I and IV (all
      P < 0.05) and the level of MDA of Group III was significantly lower than that of
      Group II too (P < 0.05). The water contents of Group II and III were both
      significantly lower than those of Groups I and IV (all P < 0.05). The numbers of
      TUNEL positive cell and apoptotic cells of Group II and III were all
      significantly lower than those of Groups I and IV (all P < 0.05). CONCLUSIONS:
      PKC can be activated by transient ischemia and PMA. PKC protects the heart
      function effectively.

PMID- 16796841
TI  - [Effect of stent coated with diallyl trisulfide on endothelial structure and
      function after coronary injury: experiment with dogs].
AB  - OBJECTIVE: To investigate the effect of stent coated with diallyl trisulfide on
      endothelial structure and function after coronary injury. METHODS: Eight adult
      dogs were randomly divided into 2 equal groups to undergo implantation of stent
      coated with diallyl trisulfide (drug group) or stent not coated with diallyl
      trisulfide (control group) into the distal and proximal ends of the left
      circumflex coronary arteries respectively. Twenty-eight hours later the dogs were
      killed. Their coronary arteries with the stents inside were taken out and divided
      into 4 parts: 2 parts underwent light microscopy and scanning electron microscopy
      and 2 parts underwent immunohistochemistry and Western blotting to examine the
      levels of endothelial nitric oxide synthase (eNOS) and nitrogen monoxide (NO).
      RESULTS: The thickness of intima of the control group was 0.35 mm +/- 0.11 mm,
      significantly greater than that of the drug group (0.12 mm +/- 0.05 mm, P <
      0.01); the area of intima of the control group was 1.81 mm(2) +/- 0.36 mm(2),
      significantly greater than that of the drug group (1.17 mm(2) +/- 0.25 mm(2), P <
      0.05). The endothelial cells in the intima of the drug group were tighter and
      more orderly than those of the control group. Immunohistochemistry showed that
      the eNOS protein expression of the drug group was 11.1 +/- 1.9, significantly
      higher than that of the control group (5.6 +/- 0.6, P < 0.01). Western blotting
      showed that the eNOS protein expression of the drug group was 37.5 +/- 6.2,
      significantly higher than that of the control group (10.4 +/- 2.7, P < 0.01). The
      NO level of the drug group was 279 micromol/L +/- 72 micromol/L. significantly
      higher than that of the control group (60 micromol/L +/- 57 72 micromol/L, P =
      0.01). CONCLUSION: Stent coated with diallyl trisulfide promotes the
      endothelialization and expression of eNOS, and raises the NO level. While
      promoting the recovery of the endothelial structure, stent coated with diallyl
      trisulfide promotes the recovery of endothelial function.

PMID- 16796842
TI  - [Experimental research on establishing chronic ischemic heart failure model of
      minipig with intracoronary perfusion of plastic microspheres by catheterization].
AB  - OBJECTIVE: To establish a stable chronic ischemic heart failure (CIHF) model of
      minipig caused by gradual myocardial ischemia and necrosis that was achieved with
      repetitive microspheres perfusion in left anterior descending artery (LAD).
      METHODS: A total of fifteen Wuzhishan minipigs original in Hainan China (8 to 11
      months old with body weight of 20 to 30 kg) were used. The 4F angiographic
      catheter was superselectively engaged in LAD, and 1 ml of suspending plastic
      microspheres fluid were given repeatedly at ten-minute intervals, which include
      microspheres 1.0 x 10(5)/ml, until LVEDP raising and maintaining from 15 mm Hg to
      18 mm Hg and TIMI flow was less than or equal to grade 2. Electrocardiography,
      hemodynamic parameters, CK-MB and cTnT were monitored during the procedure. LVEF
      was repeatedly measured with ultracardiography at 10 d, 20 d, 30 d, 40 d, 50 d,
      60 d after establishing chronic ischemic heart failure model. Meanwhile,
      hemodynamic indices including mRAP, mRVP, mPAP, PCWP and CO (thermo-dilution
      method) were measured before and two months after procedure. The success rate,
      stability and repetition of chronic ischemic heart failure model were identified
      and evaluated. Finally, myocardial infarcted area was measured and myocardial
      pathologic examination was investigated. RESULTS: Eleven minipigs survived two
      months after procedure. There were ten minipigs accorded with the criteria (LVEDP
      > 18 mm Hg CO reduced by 30%) of the CIHF model and the success rate was 66.7%
      with a mean of 3.2 +/- 0.9 times of microspheres injections and total doses of
      (3.2 +/- 0.9) x 10(5) microspheres. This resulted in 38.5% reduction in LVEF,
      197.8% elevation in LVEDP and 46.8% declining in CO from baseline values (P <
      0.01), while mRAP, mRVP, mPAP and PCWP increased significantly as compared with
      those before procedure. Cross myocardium pathology showed the ratio of necrosis
      area to left ventricle (LV) area was 25.4% - 34.9% (mean 28.6%) and light
      microscopy examination of LV myocardium revealed that intravascular
      semitransparent plastic microspheres distributed throughout subendocardium of
      left ventricular anterior and apical parts, with more numerous focal myofiber
      necrosis, which characterized by pathologic founding of ischemic necrosis of
      myocardium with fibre proliferation. CONCLUSION: A stable CIHF model could be
      established in Chinese Wuzhishan minipigs with intra-coronary microspheres
      perfusion via superselectively engaging in LAD, which was prior to those of drug
      induced, tachycardia-pacing induced or coronary artery ligation-induced, and had
      the advantages of stability, closed chest, mild trauma higher success rate and
      easy for repetition. It might be suitable for using the research of CIHF as large
      reliable experimental animal model.

PMID- 16796846
TI  - [Effects of RNA interference targeting angiotensin 1a receptor on the blood
      pressure and cardiac hypertrophy of rats with 2K1C hypertension].
AB  - OBJECTIVE: To investigate the effects of RNA interference (RNAi) targeting
      angiotensin 1a (AT1a) receptor on the blood pressure and cardiac hypertrophy of
      rats with 2K1C (2-kidney, 1-clip) hypertension. METHODS: Two kinds of RNAi
      plasmids, pAT1a-shRNA1 carrying an U6 promoter and an AT1a-specific shRNA-coding
      template sequence corresponding the sites 928 - 946 and pAT1a-shRNA2 carrying an
      U6 promoter and an AT1a-specific shRNA-coding template sequence corresponding the
      sites 978 - 996, and a blank plasmid pCon carrying a nonspecific shRNA-coding
      sequence were constructed. Thirty Sprague-Dawley rats underwent clipping of the
      left renal artery so as to establish two-kidney, one-clip (2K1C) hypertension
      models and then were randomly divided into 5 equal groups: pAT1a-shRNA1 group
      (injected with pAT1a-shRNA1 4 mg/kg only one time), pAT1a-shRNA2 group (injected
      with pAT1a-shRNA2 4 mg/kg only one time), pCon group (injected with pCon 4 mg/kg
      only one time), valsartan group (perfused into the stomach with valsartan, a AT1
      receptor inhibitor 30 mg.kg(-1).d(-1), for 3 weeks), and control blank group
      (without any treatment). Three weeks later, the systolic pressure of the caudal
      artery was measured, catheterization through carotid artery was conducted to
      measure the systolic blood pressure (SBP) and diastolic blood pressure (DBP), and
      the left ventricular pressure curve was drawn. Then the rats were killed; the
      weight of the heart was measured, the ratio of left ventricle weight to body
      weight (LV/BW) was calculated, and pathological examination of the heart and
      thoracic aorta was performed. Western blotting was used to detect the protein
      expression of AT21 in the ventricle and aorta. Six age-matched healthy rats were
      used as normal controls. RESULTS: There was no significant difference in the
      caudal artery pressure among the 5 groups (all P > 0.05) before intervention.
      Three weeks later the caudal artery pressures of the blank control group and pCon
      group continued to significantly increase by about 25 mm Hg compared to the
      values before the intervention (both P < 0.001) and without significant
      difference between these 2 groups; however, the caudal artery pressures of the
      pAT1a-shRNA1, pAT1a-shRNA2, and valsartan groups were 15.1 mm Hg +/- 5.4 mm Hg,
      16.4 mm Hg +/- 8.4 mm Hg, and 30.6 mm Hg +/- 18.2 mm Hg lower than those before
      the intervention respectively (all P < 0.01); and were also significantly lower
      than those of the blank groups (P < 0.01 or P < 0.05). There was no significant
      differences in the +/- dp/dt value and indicators of renal function among these
      groups. The carotid artery pressure of the pAT1a-shRNA1, pAT1a-shRNA2, and
      valsartan groups were 194 mm Hg +/- 5 mm Hg, 200 mm Hg +/- 5 mm Hg, and 164 mm Hg
      +/- 5 mm Hg, all significantly lower than those of the blank and pCon groups (234
      mm Hg +/- 10 mm Hg and 232 mm Hg +/- 7 mm Hg respectively, all P < 0.01). The
      LV/BW of the pAT1a-shRNA1, pAT1a-shRNA2, and valsartan groups were 2.27 +/- 0.37,
      2.31 +/- 0.26, and 2.26 +/- 0.39, all significantly lower than that of the blank
      and pCon groups (3.24 +/- 0.38 and 2.94 +/- 0.06, respectively, all P < 0.01),
      similar to that of the normal control group (P > 0.05). The myocardiocytes were
      significantly hypertrophic and the arterial tunica media was significantly
      thickened in the blank group and such changes were all improved to different
      degrees in the pAT1a-shRNA1, pAT1a-shRNA2, and valsartan groups. The protein
      expression levels of AT1 receptor in the myocardium of the pAT1a-shRNA and pAT1a
      shRNA2 groups were lower by 53.3% and 47.8% respectively than that of the blank
      group, and the protein expression levels of AT1 receptor in the thoracic aorta of
      the pAT1a-shRNA and pAT1a-shRNA2 groups were lower by 58.7% and 49.3%
      respectively than that of the blank group (all P < 0.01); however, there were no
      significant difference in the protein expression levels of AT1 receptor in the
      myocardium and thoracic aorta between the valsartan and blank groups (both P >
      0.05). CONCLUSION: RNA interference targeting AT1a receptor inhibits the
      development of renovascular hypertension and the accompanying cardiac
      hypertrophy. The RNAi technology may become a new strategy of gene therapy for
      hypertension.

PMID- 16796847
TI  - [Association of aldosterone synthase gene -344T/C polymorphism with plasma
      aldosterone and angiotensin II concentration in hypertensive patients].
AB  - OBJECTIVE: To investigate the association of aldosterone synthase (CYP11B2) 
      344T/C polymorphism with plasma renin activity (PRA), and concentrations of
      angiotensin II (Ang II) and aldosterone (Aldo) in patients with essential
      hypertension (EH). METHODS: 421 EH patients, 296 males and 125 females, aged 56.3
      +/- 11.2, and 207 sex and aged-matched normotensive subjects were genotyped for
      the CYP11B2 -344T/C polymorphism by polymerase chain reaction-restriction
      fragment length polymorphism. PRA and plasma Ang II and Aldo concentrations were
      measured by radioimmunoassay among 328 EH patients in the supine position and 279
      of the 328 subjects in the upright position. RESULTS: No significant difference
      in genotype and allele frequencies of CYP11B2 -344T/C polymorphism was observed
      between the EH and normotensive subjects (P = 0.61 and P = 0.34 respectively). In
      the 328 EH patients undergoing measurement of PRA, Ang II, and Aldo, the plasma
      Aldo concentration of the TT subjects was 76.8 pg/ml, significantly higher than
      those of the TC subjects (58.8 pg/ml) and CC subjects (58.8 pg/ml, P = 0.02),
      after adjustment for age, sex and body mass index. No association was found
      between the -344T/C polymorphism and PRA and plasma Ang II in the supine position
      (P = 0.63 and P = 0.28 respectively). However, with similar adjustment applied,
      the plasma Ang II concentration in the upright position was higher in the CC
      subjects (85.7 pg/ml) than in the TC subjects (54.6 pg/ml) and TT subjects (51.8
      pg/ml. P = 0.02). CONCLUSION: In the EH patients, CYP11B2 -344T/C polymorphism is
      associated with plasma Aldo and the plasma Ang II concentration when the patients
      are in the upright position.

PMID- 16796849
TI  - [Current status of primary hypertension in China: an epidemiological study of 12
      provinces, 1 autonomous regions, and 1 municipality].
AB  - OBJECTIVE: To investigate the current prevalence of primary hypertension in China
      in 2002 so as to lay a foundation for further control of hypertension in future.
      METHODS: Physical examination, including measurement of the blood pressure using
      international standardized methods especially, was conducted among 29,076 persons
      aged 35 - 85, 13,555 males (46.6%) and 15,521 females (53.4%), by cluster
      sampling in Tianjin, Inner Mongolia, Shanxi, Henan, Shandong, Hubei, Hunan,
      Sichuan, Guangdong, Jiangxi, Yunnan, and Shaanxi. RESULTS: The prevalence of
      hypertension was 27.9% in general. The prevalence increased along with the age.
      The rate of awareness of being ill with hypertension was 60.71% in general
      (9872/29,076), and was 55.64% among the males, significantly lower than that
      among the females (65.42, P < 0.001). The treatment rate 49.65% (4901/9872) in
      general, and was significantly higher among the females than among the males (P <
      0.01). The control rate was 5.7% (562/9872). In general, the prevalence of
      hypertension was higher in the North than in the South, and was becoming lower
      and lower from the North to the South. CONCLUSION: The prevalence of hypertension
      is high, while the rates of awareness, treatment and control are low in China.

PMID- 16796850
TI  - [Enhancing evidence-based medicine practice to promote the quality of clinical
      care].

PMID- 16796851
TI  - [Myocardial fibrosis: a new target for heart failure therapy].

PMID- 16796852
TI  - [Progress in the research of targets for the molecular immunotherapy in dilated
      cardiomyopathy].

PMID- 16796854
TI  - [Analysis of influencing factors of decision making of emergent public health
      events].

PMID- 16796855
TI  - [The clinical value of B-type natriuretic peptide in the diagnosis of left heart
      failure].
AB  - OBJECTIVE: To evaluate the diagnostic value of B-type natriuretic peptide (BNP)
      in the diagnosis of left heart failure (HF) or left ventricular systolic
      dysfunction. METHODS: Samples of peripheral venous blood were collected from 243
      consecutive patients with left HF and 111 normal controls (control group, CG) to
      measured BNP level with fluorescence immunoassay method. The patients with left
      HF were divided into 2 groups: those with the left ventricular ejection fraction
      (LVEF) </= 40% (n = 111) and those with the LVEF > 40% (n = 132) according to the
      level of LVEF; or into 2 groups: compensated heart failure group (CHF group, at
      NYHA grade I - II, n = 110) and decompensated heart failure group (DHF group, at
      NYHA grade III - IV, n = 133) according to the New York Heart Association (NYHA)
      functional class. RESULTS: The plasma level of BNP of the left HF group was 292.0
      ng/L, significantly higher than that of the CG (17.9 ng/L, P < 0.001). The plasma
      BNP of the group with the LVEF </= 40% was 471.0 ng/L, significantly than that of
      the group with the LVEF > 40% (138.5 ng/L, P < 0.001). The plasma BNP of the DHF
      group was 579.0 ng/L, significantly higher than that of the of the CHF group
      (84.8 ng/L, P < 0.001). The values of area under the curve (AUC) of receiver
      operator characteristic curve were all > 0.9 in the diagnosis of presence of HF
      (AUC = 0.927), HF with the LVEF </= 40% (AUC = 0.989), and DHF (AUC = 0.991), and
      in the differential diagnosis between CHF and DHF (AUC = 0.941). When 90.0 pg/ml
      was used as cutoff value to diagnose left HF, heart failure with the LVEF </=
      40%, and decompensation, the positive predictive value (PPV) were 98.9%, 98.1%,
      and 98.5% respectively, and the negative predictive value (NPV) were 64.5%,
      94.0%, and 96.5% respectively. When 50.0 pg/ml was used as the cutoff value to
      diagnose HF with the LVEF > 40% and compensated heart failure, the PPV were 88.0%
      and 84.7%, the NPV were 72.6% and 72.1% respectively. CONCLUSION: The diagnostic
      value of BNP is high for the diagnosis of more severely impaired LVEF and
      decompensated heart failure with 90.0 pg/ml as the cutoff value, and if 50.0
      pg/ml is used as the cutoff value, the value is also good for the diagnosis of HF
      with the LVEF > 40% and compensated heart failure.

PMID- 16796856
TI  - [Effects of cardiac sympathetic blockade on left ventricular diastolic function
      in patients with dilated cardiomyopathy and severe heart failure].
AB  - OBJECTIVE: To investigate the effects of cardiac sympathetic blockade on left
      ventricular diastolic function in patients with dilated cardiomyopathy and severe
      heart failure (HF). METHODS: Thirty-nine consecutive patients with dilated
      cardiomyopathy and severe HF with a left ventricular ejection fraction < 35% were
      randomly divided into 2 groups: control group (n = 16, 12 males and 4 females,
      aged 56 +/- 16, undergoing routine anti-HF treatment), and cardiac sympathetic
      blockade (TEB) group (n = 23, 18 males and 5 females, aged 51 +/- 13, undergoing
      sympathectomy at the interspinal space T3 - 4 or T4 - 5 in addition to the
      routine anti-HF treatment). Transthoracic echocardiography was conducted before
      the treatment and 1 month after the treatment to measure the left atrial diameter
      (Lad), left ventricular diastolic end diameter (LVDEd), ejection fraction (EF),
      peak early and late diastolic mitral inflow velocity (Em and Am) at 6 mitral
      annular sites, and the mean values of Em and Am (MEm and MAm). RESULTS: The Lad
      of the TEB group was 40.4 +/- 5.3 mm, significantly shorter than that of the
      control group (45.2 mm +/- 7.3 mm. P < 0.05). The LEDEd of the TEB group was 66
      mm +/- 6 mm, significantly shorter than that of the control group (71 mm +/- 6
      mm, P < 0.05). The EF of the TEB group was 35% +/- 7%, significantly higher than
      that of the control group (23% +/- 6%, P < 0.05). The MEm of the TEB group was
      5.7 cm/s +/- 1.5 cm/s, significantly faster than that of the control group (7.1
      cm/s +/- 1.7 cm/s, P < 0.05); and the MAm of the TEB group was 7.1 cm/s +/- 2.1
      cm/s, significantly faster than that of the control group (5.4 cm/s +/- 1.8 cm/s,
      P < 0.05). In the control group the values of Lad, LVDEd, EF, Am, MEm, and MAm
      did not change significantly, and the Em values significantly increased only at 2
      mitral annular sites after the treatment. CONCLUSION: Sympathetic blockade
      reduces the left ventricular cavity and boosts up the ejection performance, thus
      improving the left ventricular diastolic function.

PMID- 16796857
TI  - [Treatment of chronic heart failure by overexpressing sarcoplasmic reticulum
      calcium ATPase through gene therapy: an experiment with rats].
AB  - OBJECTIVE: To evaluate the value of sarcoplasmic reticulum Ca(2+)-ATPase
      (SERCA2a) in the gene therapy of congestive heart failure. METHODS: (1) The
      abdominal aortas of 51 male SD rats were isolated and ligated so as to establish
      models of heart failure caused by contraction of abdominal aortas. 20 rats
      undergoing isolation of the abdominal aorta without ligation were used as
      controls. 18 approximately 20 days after the operation heart failure occurred,
      then the rats with contraction of abdominal aorta and heart failure were randomly
      divided into 3 groups: rAAV-SERCA2a group (recombinant adeno-associated virus
      containing SERCA2a cDNA, rAAV-SERCA2a, of the concentration of 2 x 10(11) v.g was
      injected via diaphragm into the pericardia cavity), heart failure control group
      (without trentment) and rAAV2-EGFP group (the control virus rAAV2-EGFP of the
      concentration of 2 x 10(11) v.g was injected via diaphragm into the pericardial
      cavity). 10 and 30 days after virus injection, a catheter was inserted through
      the jugular vein into the left ventricle to record the left ventricle systole
      pressure (LVSP), left ventricle end diastole pressure (LVEDP), left ventricle
      pressure maximum increase speed (+dp/dt), and left ventricle pressure maximum
      decrease speed (-dp/dt), and heart rate (HR). Then all the rats were killed and
      their hearts were taken out to examine the expression of the SERCA2a protein. (2)
      The left coronary arteries of 25 male SD rats were ligated so as to establish the
      models of cardiac infarction. 9 rats underwent isolation of the left coronary
      arteries without ligation and were used as controls. Four weeks after the
      operation thoracotomy was performed on the rats with heart failure caused by
      heart infarction, rAV-SERCA2a or rAV2-EGFP were injected into the myocardium, and
      dilute solution was injected to the control rats. 21 days later all the rats were
      performed hemodynamic exams. RESULTS: (1) Thirty days after the transfection the
      LVSP, +dp/dt, and -dp/dt of the rAAV-SERCA2a group were significantly higher than
      those of the rAAV2-EGFP group by 57% (94 mm Hg vs 147 mm Hg), 110% (5350 mm Hg/s
      vs 11 225 mm Hg/s), and 99.8% (4198 mm Hg/s vs 8390 mm Hg/s) respectively,
      meanwhile the LVEDP was significantly lower by 60% (22 mm Hg vs 9 mm Hg). These
      homodynamic parameters of the rAAV-SERCA2a group were not significantly different
      from those of the control group. Thirty days after transfection the expression of
      SERCA2a protein of the SERCA2a group was significantly higher than those of the
      control heart failure and rAAV2-EGFP groups. (2) Twenty-one days after the
      transfection, the LVSP, +dp/dt, and -dp/dt of the SERCA2a group were
      significantly higher than those of the control group by 28% (86 mm Hg vs 110 mm
      Hg), 41% (4272 mm Hg/s vs 6026 mm Hg/s), and 71% (2789 mm Hg/s vs 4756 mm Hg/s)
      respectively, and the LVEDP was significantly lower by 70% (3.89 mm Hg vs -5.34
      mm Hg), however, these homodynamic parameters of the rAV-SERCA2a group were all
      worse compared with the control false operation group. CONCLUSION: The
      recombinant viruses, rAAV-SERCA2a and rAV-SERCA2a, effectively deliver the
      SERCA2a gene and improve the homodynamic state.

PMID- 16796858
TI  - [Long-term impact of transfer of phrenic nerve on respiratory system of children:
      a clinical study of 34 cases].
AB  - OBJECTIVE: To study the long-term impact of transfer of phrenic nerve on
      respiratory system of children. METHODS: Thirty-four children with brachial
      plexus injury, 25 boys and 9 girls, underwent transfer of phrenic nerve and were
      divided into 3 groups according to the age when they underwent operation: group
      of the age of 0 - 12 months (n = 17), group of 13 - 36 months (n = 11), and group
      of 37 - 60 months (n = 6). Thirty-four sex, height, and body weight-matched
      healthy children were used as controls. Follow-up, including physical
      examination, pulmonary function examination (tidal volume, ventilation, etc),
      blood gas analysis, and chest radiography, was conducted for 4.03 years (3 - 7
      years). RESULTS: The values of maximum vital capacity of the group of 0 - 12
      months and group of 13 - 36 months were 1.0 L +/- 0.2 L and 1.2 L +/- 0.4 L, both
      significantly lower than those of the corresponding control groups (1.3 L +/- 0.3
      L and 1.4 L +/- 0.5 L, both P < 0.05). The values of one-second vital capacity of
      the group of 0 - 12 months and group of 13 - 36 months were 0.8 L +/- 0.1 L and
      0.9 L +/- 0.1 L, both significantly lower than those of the corresponding control
      groups (1.0 L +/- 0.1 L and 1.0 L +/- 0.1 L, both P < 0.05). However, the values
      of the maximum vital capacity and one-second vital capacity of the group of 37 -
      60 months were 1.6 L +/- 0.3 L and 1.8 L +/- 0.5 L respectively, both not
      significantly different from those of the controls (both P > 0.05). The results
      of blood gas analysis of the 3 operation groups were not significantly different
      from those of the corresponding controls. Chest radiograph showed that the
      diaphragm top was raised by 1.93 intercostal spaces (0.5 - 3.5 intercostal
      spaces) in comparison with the contralateral sides with significant differences
      between the group of 0 - 12 months and the group of 13 - 36 months and between
      the group of 0 - 12 months and the group of 37 - 60 months (both P < 0.05). The
      recurrent respiratory infection rate and of the groups of 0 - 12 months and 13 -
      36 months were 47.1% and 27.3% respectively, both significantly higher than that
      of the group of 37 - 60 months (0%). The thorax deformity rate of the groups of 0
      - 12 months and 13 - 36 months were 41.2% and 9.1% respectively, both
      significantly higher than that of the group of 37 - 60 months (0%). Three of the
      children in the group of 0 - 12 months (17.6%) had digestive system symptoms.
      CONCLUSION: Transfer of phrenic nerve operated on children younger than 3 years
      may cause abnormalities of respiratory system, thorax, and digestive system. The
      younger the patients the more severe the consequences of the operation. The
      children older than 3 years tolerate the operation better.

PMID- 16796859
TI  - [Histopathologic study of the ethmoid bone in chronic sinusitis].
AB  - OBJECTIVE: To investigate the histopathologic study of the ethmoid bone in
      chronic sinusitis (CRS) and the role of bone pathology in the pathogenesis of
      CRS. METHODS: Specimens of mucosa of ethmoid sinus with bone were collected
      during operation from 40 patients with CRS, 25 males and 15 females, aged 44.8,
      and specimens of mucosa of ethmoid sinus were collected from 16 patients with
      other otorhinolaryngologic diseases, 9 males and 7 females, aged 40.9 during
      operation. The specimens underwent HE, tartrate-resistant acid phosphatase,
      alkaline phosphatase, and Van Gieson staining so as to obtain the scores of nasal
      mucosa inflammation, pathology of mucoperiosteum and bone, and activity of bone
      remodeling. RESULTS: The average score of mucosal inflammation of the CRS group
      was 2.30 +/- 0.88, significantly higher than that of the control group (1.38 +/-
      0.81, P = 0.004). The score of mucoperiosteum and bone pathology of the CRS group
      was 1.65 +/- 0.84, significantly higher than that of the control group (1.00 +/-
      0.73, P = 0.004). The score of bone remodeling activity of the CRS group was 2.15
      +/- 0.74, significantly higher than that of the control group (1.56 +/- 0.63, P =
      0.007). In the CRS patients, the score of mucosal inflammation was not
      significantly correlated with the mucoperiosteum and bone pathology (R = 0.047, P
      = 0.772), and the activity of bone remodeling (R = 0.021, P = 0.897). CONCLUSION:
      The ethmoid bone of CRS patients shows marked fibrosis, bone remodeling,
      structure of woven bone, and pathologic changes similar to those of chronic
      osteomyelitis, especially bone absorption, new bone formation, etc.

PMID- 16796860
TI  - [Current infection of Mycoplasma pneumoniae in adults: clinical analysis of 13
      hospitalized patients].
AB  - OBJECTIVE: To investigate the clinical characteristics of Mycoplasma pneumoniae
      (MP) current infection in adults. METHODS: The clinical data of 13 patients in
      Beijing, 7 males and 6 females, aged 21.9 (17 - 34), hospitalized from April 2003
      to April 2004, were reviewed retrospectively. RESULTS: Seven of the 13 patients
      were the schoolmates of the same military school, 3 being in the same class but
      not living in the same dormitory, 3 being hospitalized with an interval of 5 days
      and 2 with an interval of 2 days. A 4-fold or higher titer rise was found 16 - 17
      days after the onset of symptoms. Six cases showed antibody negative at the first
      visit (2 - 8 days after the onset). The most common symptoms included fever
      (13/13), cough (11/13), mild headache (5/13), and sore throat (5/13). No symptoms
      of sneeze, nasal obstruction, skin rash, and ear pain were found. There was no
      leukocytosis. Ten patients had pneumonia confirmed by X-ray examination.
      Appropriate macrolide plus quinolones were effective in the treatment. However,
      there was no significant difference between the curative effect of erythromycin
      and that of azithromycin. CONCLUSION: MP mainly attacks young people and mainly
      causes pneumonia. Extrapulmonary complication is rare. It is not advisable to use
      a single high antibody titer as the criterion for diagnosis of MP current
      infection.

PMID- 16796861
TI  - [High mobility group box-1 protein activates endothelial cells to produce
      cytokines and has synergistic effect with lipopolysaccharide in inducing
      interleukin-6 release].
AB  - OBJECTIVE: To observe the effects of high mobility group box 1 (HMGB1) protein on
      the release of cytokines of human umbilic vein endothelial cells (HUVECs) and the
      expression of interleukin-6 (IL-6) induced by lipopolysaccharide (LPS). METHODS:
      HUVECs were cultured and then divided into the following groups. (1) Recombinant
      HMGB1 protein of the terminal concentration of 15 ng/ml was added into the
      culture fluid of HUVECs, 24 hours later the supernatant was collected to detect
      the levels of granulocyte/macrophage colony stimulating factor (GM-CSF),
      interferon-gamma (IFN-gamma), and interleukin-10, IL-12, IL-1beta, IL-2, IL-4, IL
      6, and IL-8, by using LiquiChip system. (2) HMGB1 protein of the terminal
      concentrations of 3, 15, or 75 ng/ml was added into the culture fluid of the
      HUVECs, 24 hours later the supernatants were collected to detect the level of IL
      6. (3) HMGB1 protein of the terminal concentration of 15 ng/ml was added into the
      culture fluid of HUVECs, 1, 3, 6, 12, and 24 hours after the stimulation the
      supernatant was collected to detect the level of IL-6. (4) The culture fluid of
      HUVECs was added with HMGB1 protein of the terminal concentration of 15 ng/ml
      and/or LPS of the concentration of 10 ng/ml, 24 hours later the supernatant was
      collected to detect the level of IL-6. Culture fluid not added with HMGB1 protein
      was used as control in any kind of test. RESULTS: (1) The levels of GM-CSF, IFN
      gamma, IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) secreted by the
      HMGB1 stimulated HUVECs were 5, 7, 4.2, 27.8, 12.8, and 5.4 times that of those
      control group (all P < 0.01) (2) The levels of IL-6 secreted by the HUVECs
      stimulated with HMGB1 protein of the concentrations of 3, 15 and 75 ng/ml
      respectively were 155 pg/ml +/- 33 pg/ml, 901 pg/ml +/- 184 pg/ml, and 1508 pg/ml
      +/- 379 pg/ml respectively, all significantly higher than that of the control
      group (32 pg/ml +/- 21 pg/ml, all P < 0.01). (3) Since 3 h after the stimulation
      of HMGB1 protein the level of IL-6 began to increase gradually. 6, 12, and 24
      hours after the stimulation the levels of IL-6 secreted by the HUVEC were 75
      pg/ml +/- 22 pg/ml, 453 pg/ml +/- 78 pg/ml, and 901 pg/ml +/- 184 pg/ml
      respectively, all significantly higher than that of the control group (32 pg/ml
      +/- 21 pg/ml, all P < 0.01). (4) When the HUVECs were stimulated individually by
      LPS (10 ng/ml) or HMGB1 (15 ng/ml), the levels of IL-6 increased to 289 pg/ml +/-
      42 pg/ml and 901 pg/ml +/- 183.6 pg/ml respectively (both P < 0.01); when the
      HUVECs were costimulated by LPS and HMGB1, the level of IL-6 increased to 2360
      pg/ml +/- 299 pg/ml, which showing that there was a synergistic effect between
      HMGB and LPS (F = 69.405, P < 0.001). CONCLUSION: HMGB1 activates HUVECs to
      produce multiple inflammatory cytokines and induces HUVEC to secret IL-6 in a
      dose- and time-dependent manner. HMGB1 can also act synergistically with LPS in
      inducing IL-6 release, which may play an important role in the development of
      sepsis.

PMID- 16796862
TI  - [Monthly distribution of insomnia patients' birth].
AB  - OBJECTIVE: To investigate whether the monthly distribution of birth is associated
      with insomnia. METHODS: The monthly distribution of birth of 1020 consequent
      patients with insomnia who visited the Third Hospital of Peking University, 439
      males and 581 females, aged 54 (22 - 86), was investigated and compared with that
      of 13254 cases of healthy newborn children born in the same hospital 1994 - 2004.
      RESULTS: 114 of the 1020 patients with insomnia were been born in January
      (11.2%), 90 in February (8.85%), 65 in March (6.4%), 67 in April (6.6%), 56 in
      May (5.5%), 56 in June (5.5%), 66 in July (6.5%), 78 in August (7.6%), 64 in
      September (6.3%), 91 in October (8.9%), 126 in November (12.4%), and 147 in
      December (14.4%). The structural ratio of the number of insomnia patients was the
      highest for those who were born in the months November, December, and January,
      and was the lowest for those who were born in May, June, and July. The number of
      insomnia patients who were born in the wintery months, November, December, and
      January, was 387 (37.9%), much more than those who were born in the May, June,
      and July (178 cases, 17.4%). The structural ratios of the insomnia patients who
      were born in different months were not significantly different between the 2
      sexes (chi(2) = 12.769, P > 0.05). There was no significant differences in the
      structural ratios of the number of healthy newborn children who were born in
      different months. However, the monthly distribution of birth of the patients was
      statistically significantly different between the patients with insomnia and the
      healthy newborn children (chi(2) = 75.098, P < 0.01). CONCLUSION: Month of birth
      is associated with insomnia. Those born in November, December, and January are
      more susceptible to insomnia.

PMID- 16796875
TI  - [We should prevent the complications of bile duct of liver transplantation].

PMID- 16796876
TI  - [Indication of liver transplantation for hepatocellular carcinoma: Shanghai Fudan
      Criteria].
AB  - OBJECTIVE: To evaluate the effects of different selection criteria on the
      prognosis of hepatocellular carcinoma (HCC) patients undergoing liver
      transplantation (LT) and to explore the new criteria adapted for Chinese National
      Situation. METHODS: A retrospective analysis was performed on 251 consecutive
      patients with HCC who underwent LT between April 2001 and January 2006 at our
      institution. We compared the outcome of the patients meeting different criteria
      such as milan, UCSF and the Pittsburgh modified TNM criteria. Survival rates were
      calculated using the Kaplan-Meier method, and differences between the curves were
      assessed by log-rank test. RESULTS: There was no significant difference in 1, 2,
      3-year survival rates and recurrence-free survival rates between milan criteria
      (n = 93; 86%, 77%, 77% and 91%, 86%, 86%) and UCSF criteria (n = 131; 90%, 83%,
      83% and 92%, 89%, 89%). According to Pittsburgh criteria (n = 207), the 1, 2, 3
      year survival rates and recurrence-free survival rates were 84%, 74%, 67% and
      85%, 83%, 73%, respectively. For advanced tumors (over all the criteria), the
      survival rates and recurrence-free survival rates decreased significantly (n =
      44; 65%, 43%, 43% and 47%, 43%, 43% respectively). When criteria (named as
      Shanghai Fudan Criteria) were expanded to HCC patients with solitary lesions < or
      = 9 cm in diameter, or no more than 3 lesions, the largest < or = 5 cm, with a
      total tumor diameter < or = 9 cm, there was no significant difference in 1, 2, 3
      year survival rates and recurrence-free survival rates (n = 151; 88%, 80%, 80%
      and 90%, 88%, 88%, respectively) as compared with milan criteria, but more
      patients using Shanghai Fudan Criteria could undergo liver transplantation.
      CONCLUSION: Shanghai Fudan Criteria, which expanded the tumor size limits, does
      not adversely impact survival of HCC patients after LT.

PMID- 16796877
TI  - [Analysis of the risk factors influencing the prognosis of orthotopic liver
      transplantation for hepatocellular carcinoma and summary of relevant clinical
      experience].
AB  - OBJECTIVE: To analyze the risk factors influencing the prognosis of orthotopic
      liver transplantation for hepatocellular carcinoma (HCC) and sum up the relevant
      clinical experience in diagnosis and treatment of HCC. METHODS: The clinical data
      of 198 HCC patients, 177 males and 21 females, aged 49 (24-83), were analyzed.
      RESULTS: The 0.5-, 1-, and 2-year survival rates were 89%, 78%, and 65
      respectively. The rates of disease-free survival (DFS) were 85%, 73, and 67%
      respectively. Univariate analysis revealed that tumor size, presence of vascular
      invasion, Edmondson grade, TNM classification, and preoperative alpha-fetoprotein
      (AFP) were significantly related to DFS, and the 4 foregoing factors were also
      related to the survival rate. Cox regression analysis suggested that presence of
      vascular invasion was an independent prognostic factor of survival rate and DFS.
      CONCLUSION: Vascular invasion plays a leading role in evaluating the prognosis of
      orthotopic liver transplantation for HCC. It is important to discover the micro
      metastasis and explore more effective approaches to prevent recurrence after
      transplantation.

PMID- 16796879
TI  - [Prophylaxis and management of ischemic-type biliary lesion after orthotopic
      liver transplantation].
AB  - OBJECTIVE: To investigate the cause, prophylaxis, and management of ischemic-type
      biliary lesion (ITBL) after orthotopic liver transplantation. METHODS: The
      clinical data of 212 operations of orthotopic liver transplantation on 209
      patients, 184 males and 25 females, aged 44.5 (18-69), including 3 patients
      undergoing secondary liver transplantation, between February 1999 and August 2004
      were reviewed retrospectively. RESULTS: ITBL occurred in 14 patients (6.6%),
      among whom 5 had biliary lesions of hepatic bifurcation, 3 had intrahepatic
      biliary lesions, and 6 had multiple extrahepatic and intrahepatic biliary
      lesions. The incidence rate of ITBL among the recipients of liver in cold storage
      for more than 10 hours, with donor-recipient ABO blood type incompatibility, with
      postoperative hepatic arterial lesions, and with hepatitis B related hepatic
      failure as the primary disease were 9.8% (10/102), 22.2% (2/9), 40% (2/5), and
      14.6% (7/48) respectively. The 14 patients with ITBL were managed with
      conservative treatment, endoscopy, Roux-en-Y anastomosis, or re-transplantation.
      Seven of the 14 patients were cured, the condition of 5 patients was improved,
      and 1 patient died with a mortality of 7.1% (1/14). The incidence of ITBL-related
      graft loss was 23% (3/14). CONCLUSION: It is crucial to avoid too long
      preservation time of donor liver and donor-recipient ABO blood type
      incompatibility, and timely management of postoperative hepatic arterial lesions
      so as to prevent ITBL. Proper treatment for ITBL should be chosen according to
      the specific conditions of the lesion of biliary duct tree.

PMID- 16796881
TI  - [Effects of splenectomy on patients undergoing liver transplantation].
AB  - OBJECTIVE: To investigate the effects of splenectomy before or simultaneously in
      liver transplantation on the outcome of liver transplantation. METHODS:
      Splenectomy was performed on 29 of the consecutive 403 patients undergoing
      orthotopic liver transplantation (OLT) between February 1999 and May 2005, before
      the OTC in 23 of which and simultaneously during the OTC in 6 of which. Fifty
      eight randomized selected age-matched patients undergoing OTC within the same
      period but without splenectomy were used as controls. The operation time,
      bleeding amount, transfusion amount, infection, acute rejection, survival rate,
      and post-operative recovery of platelet were compared between these groups.
      RESULTS: The average operation times of the pre-operatively splenectomized group
      (Group A) and intra-operatively splenectomized group (Group B) were 448.70 +/-
      100.51 minutes and 526.67 +/- 99.93 minutes respectively, both significantly
      longer than that of the non-splenectomized group (Group C) (362.80 +/- 71.65
      minutes, both P < 0.001). The intra-operative bleeding amount of the 2
      splenectomized groups were both longer than that of the control group, however,
      not significantly. The intra-operative transfusion amounts of Group B was 3983 +/
      1885 ml, significantly more than that of Group C (2361 +/- 1246 ml, P < 0.05).
      The plasma transfusion amount of Group B was 8387 +/- 4231 ml, significantly more
      than that of Group C (4906 +/- 3108 ml, P < 0.05). The concentrated erythrocyte
      transfusion amount of Group A was 14.2 +/- 14.6 U, significantly more than that
      of Group C (5.1 +/- 6.6 U, P < 0.001). The bacterial infection rates of the
      Groups A and B were 91.3% and 100% respectively, both significantly higher than
      that of Group C (69.0%, both P < 0.05). The mycotic infection rates of the 2
      splenectomized groups were 13% and 33.33% respectively, both significantly higher
      than that of Group C (29.3%), however, both not significantly. Acute rejection
      rate did not occurred in the 2 splenectomized groups, and in 4 cases of the non
      splenectomized group, however, without significant differences among them. The
      post-operative bleeding rate of Group B was significantly higher than that of
      Group C (P < 0.05). The accumulative survival of Group C was significantly higher
      than that of Group B (P = 0.0001). The platelet counts 14 and 20 days after
      operation of the 2 splenectomized groups were all significantly higher than those
      of the non-splenectomized group (all P < 0.05), and were higher than the normal
      levels in some cases. CONCLUSION: Splenectomy does not benefit the patients
      undergoing liver transplantation whenever it is performed before or
      simultaneously in the liver transplantation.

PMID- 16796882
TI  - [How brain-dead state affects the hepatic morphology and function of Ba-Ma mini
      pigs and its mechanism].
AB  - OBJECTIVE: To investigate the impact of brain death (BD) on the morphology and
      function of liver. METHODS: Fifteen Ba-ma minipigs were randomly divided into 3
      equal groups: brain death group (Group B) made into BD models by increasing the
      intracranial pressure; breviscapine pretreatment group (Group P), with
      breviscapine 2.5 mg x kg(-1) given intravenous drip 1-2 hours after the
      successful establishment of BD model; and control group (Group C) undergoing
      operation similar to that in Group B but without increasing the intracranial
      pressure. 3, 6, 12, 18, and 24 hours after the initial confirmation of BD blood
      samples were collected from the superior vena cava to detect the serum alanine
      transaminase (ALT), aspartate transaminase (AST), tumor necrosis factor-alpha
      (TNF-alpha), interleukin (IL)-1beta, and IL-6, and a piece of liver tissues were
      collected to undergo light microscopy and electron microscopy, and
      immunohistochemistry to examine the expression of protein kinase (PKC)-alpha by
      RT-PCR. RESULTS: The levels of serum ALT and AST of Group B began to increase
      since 12 h after BD, and were both significantly higher than those of Group C 18
      and 24 hours after BD (both P < 0.05). The levels of serum ALT and AST of Group P
      began to increase since 12 h after BD, and were both significantly lower than
      those of Group B (both P < 0.05). The levels of serum TNF-alpha, IL-1beta, and IL
      6 of Group B and Group P began to increase gradually since 3 h after BD, however,
      those of Group B were all significantly higher than those of group P (all P <
      0.05). PKC-alpha was only expressed in the plasma of a few normal liver cells.
      The PKC-alpha mRNA and protein levels of Groups B and P began to increase since 6
      h after BD, however, those of Group B were all significantly higher than those of
      Group P (all P < 0.05). Light and electron microscopy showed that only mild edema
      of liver cells was seen in Group P, and since 12 h after BD swelling of
      mitochondria, edema of liver cells, etc. were seen in Group B, and the
      morphologic damages were more severe in Group B. CONCLUSION: Brain death evokes
      hepatic functional and morphological injuries. PKC-alpha may involve in the
      mechanism. Breviscapine inhibits the activation of PKC-alpha, thus reducing the
      damage in liver.

PMID- 16796883
TI  - [Identification of hepatitis B virus integration sites in hepatocellular
      carcinoma tissues from patients with chronic hepatitis B].
AB  - OBJECTIVE: Hepatitis B virus (HBV) integration into the host genome is frequently
      detected in HBV positive hepatocellular carcinoma (HCC) in China. The aim of this
      study is to carry out a large-scale screening for the HBV integrations sites in
      HCC samples from Chinese patients. METHODS: Cellular DNA was extracted from 40
      HBV-related HCC by proteinase K digestion/phenol extraction method. One primer
      specific to HBV sequence and another primer directed to human Alu repeat were
      used to amplify the virus/cellular DNA junction. To avoid undesirable
      amplifications between Alu sequences, primers were constructed with dUTPs and
      destroyed by uracil DNA glycosylase treatment after 15 initial cycles of
      amplification. Only desirable fragments were then further amplified with specific
      primers to the known region and to a tag sequence introduced in the Alu-Specific
      primer. The PCR product was purified and subject to direct sequencing by ABI 3700
      Auto sequencer. NCBI (national center for biotechnology information) BLAST and
      MapViewer search were used for identification of HBV location on human genomes.
      RESULTS: In 40 HBsAg positive HCC samples, 34 (85%) were showed to have at least
      one copy of HBV fragment in host genome, indicating HBV-Alu-PCR is a rapid way
      for identification of new cellular DNA sequences adjacent to HBV. Analysis from
      the 68 isolated viral-cellular junctions, X gene was found to be interrupted at
      any length, not specifically at DR1 and DR2 regions. Three-prime-deleted X gene
      was observed in 65 (96%) cases. HBV preferred to integrate into the intron and
      the up-stream regulatory region of the cellular genes. In no case HBV inserted
      into the exon. Our results also demonstrated that the cellular genes targeted by
      HBV are usually key regulators of cell proliferation and cell death. Three genes,
      myeloid/lymphoid or mixed-lineage leukemia 4, G protein alpha transducing
      activity polypeptide 1 and fibronectin, were found to be recurrently targeted by
      HBV. CONCLUSION: HBV-Alu-PCR is a powerful tool for the study of HBV integration
      sites. Truncated X is a major form existed in the HBV integrants. HBV integration
      is not distributed evenly throughout the host genome and viral insertional
      mutagenesis may play an important role in the development of HCC.

PMID- 16796884
TI  - [Correlation of C-reactive protein with activity of Crohn's disease].
AB  - OBJECTIVE: To investigate the role of C-reactive protein (CRP) in evaluating
      activity of Crohn's disease (CD). METHODS: 85 patients with Crohn's disease, 59
      males and 26 females, aged 15-69, underwent laboratory examination of CRP,
      erythrocyte sedimentation rate (ESR), albumin, and hemoglobin. Crohn's disease
      activity index (CDAI) was calculated. Endoscopy was conducted to collect samples
      of colon mucosa to undergo HE staining for pathological examination and
      immunohistochemical staining for the expression of nuclear factor-kappaB p65 (NF
      kB p65). Logistic regression analysis was used to estimate the correlation of CRP
      with ESR, CDAI, endoscopic activity, pathologic activity, hypoalbuminemia, and
      anemia. The effects of lesion location, clinical severity, and drug were
      considered. RESULTS: CRP elevation was correlated with ESR, but not correlated
      with CDAI, endoscopic activity, pathologic activity, hypoalbuminemia, and anemia.
      CRP was significantly elevated in active CD (P < 0.01), especially in severe or
      colonic CD (P < 0.05). CRP rapidly decreased when the CD activity was effectively
      controlled by drugs (P < 0.01), and was reelevated when disease recurred (P >
      0.05). Serum CRP elevation was paralleled with the NF-kappaB p65 level (P = 1.0).
      CONCLUSION: More suitable for reflection of the activity of moderate or severe
      colonic CD, CRP can reflect the effects of drugs in the early stage of CD. The
      serum CRP elevation is consistent with the NF-kappaB p65 expression in colon
      tissues.

PMID- 16796885
TI  - [Newly diagnosed abnormal glucose tolerance in patients with acute coronary
      syndrome and without known diabetes mellitus].
AB  - OBJECTIVE: To investigate the prevalence of newly diagnosed abnormal glucose
      tolerance in patients with acute coronary syndrome and without known diabetes
      mellitus (DM) and to access the correlation of glycometabolic abnormality with
      traditional risk factors of cardiovascular diseases. METHODS: The clinical data
      of 1328 patients with cute coronary syndrome (ACS), without previous DM, and with
      the admission blood glucose < 11.1 mmol/ who were consecutively admitted in 52
      hospitals of 7 cities in China from June 1 to August 31 2005, were collected. A
      simple oral glucose tolerance test (OGTT) was conducted before they were
      discharged. RESULTS: Glycometabolic perturbation was seen in 887 of the 1328
      patients (67%). The prevalence rates of newly diagnosed DM and impaired glucose
      regulation (IGR) were 22% and 45% respectively. Blood pressure, blood lipid, body
      mass index, waistline, and hemoglobin A1C were all significantly higher in those
      with glycometabolic perturbation than in those with normal glucose metabolism
      (all P < 0.05). Waistline and blood lipid were the risk factors of abnormal
      glycometabolic status (both P < 0.05). CONCLUSION: Newly diagnosed DM is common
      among the ACS patients without DM history. Newly diagnosed glycometabolic status
      is associated with waistline and blood lipid.

PMID- 16796886
TI  - [Diffusion tensor imaging of the normal-appearing brain tissue in relapsing
      remitting multiple sclerosis].
AB  - OBJECTIVE: To investigate whether normal-appearing brain tissue (NABT) on
      conventional MRI has occult damage in patients with relapsing-remitting multiple
      sclerosis (RRMS) by using diffusion tensor imaging (DTI) histogram analysis, and
      to determine the correlations between DTI histogram-derived measures of the NABT
      and expanded disability status scale (EDSS) scores, disease durations, T2WI
      lesion volumes and brain tissue volumes in RRMS patients. METHODS: Conventional
      MRI and DTI scans were performed in 24 patients with RRMS and 24 sex- and age
      matched healthy controls. After segmentation of the NABT, the mean diffusivity
      (MD) and fractional anisotropy (FA) histograms of the NABT were created and
      analyzed. RESULTS: In patients with RRMS, the average MD (1.014 x 10(-3) mm2 x s(
      1)) of the NABT was higher than that (0.910 x 10(-3) mm2 x s(-1)) of control
      subjects (t = 7.238, P < 0.001); the MD histogram peak height (8.858 per
      thousand) of the NABT was lower than that (0.767 per thousand) of control
      subjects (t = 6.161, P < 0.001); the MD histogram peak location (0.809 x 10(-3)
      mm2 x s(-1)) of the NABT was higher than that (0.767 x 10(-3) mm2 x s(-1)) of
      control subjects (t = 5.324, P < 0.001); the average FA (0.231) of the NABT was
      lower than that (0.254) of control subjects (t = 6.217, P < 0.001); the FA
      histogram peak height (4.502 per thousand) of the NABT was higher than that
      (4.107 per thousand) of control subjects (t = 4.198, P < 0.001); no significant
      difference was found in the FA histogram peak location of the NABT between these
      two groups (t = 1.223, P = 0.227); none of the DTI histogram-derived measures
      correlated with EDSS scores or disease durations (P > 0.05); the average MD and
      all the FA histogram-derived measures correlated with T2WI lesion volumes (P <
      0.05); and the average MD, the MD histogram peak height and all the FA histogram
      derived measures correlated with brain tissue volumes (P < 0.05). In healthy
      controls, however, only the average FA of the NABT correlated with brain tissue
      volumes. CONCLUSION: Patients with RRMS had occult damage in the NABT and the
      extent of NABT damage was related to the lesion load of brain and to the extent
      of brain tissue atrophy.

PMID- 16796887
TI  - [Radiologic criteria of MRI in diagnosing retropharyngeal lymph nodal metastasis
      of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To explore the reasonable radiologic criteria of retropharyngeal lymph
      nodal (RLN) metastasis of nasopharyngeal carcinoma (NPC). METHODS: 275 patients
      with newly diagnosed NPC were enrolled. All patients underwent Magnetic resonance
      imaging (MRI) before treatment to measure the sizes of maximal and minimal axial
      diameters of each node. Determination of malignancy was based on the results of
      MRI follow-up. Receiver operating characteristic (ROC) curve was used to
      determine the optimal axial diameter and cutoff size criterion of RLN metastasis.
      RESULTS: Among the 275 patients, a total number of 468 RLNs were assessed. 240
      positive and 228 negative nodes were later confirmed by the MRI follow-up. The
      mean sizes of minimal and maximal axial diameters for positive nodes were
      significantly higher than those for negative nodes (9.9 mm +/- 4.8 mm vs 3.3 mm
      +/- 1.2 mm, 12.9 mm +/- 5.8 mm vs 5.7 mm +/- 2.0 mm, all P < 0.01). The
      reasonable criterion for diagnosing RLN metastasis was the minimal axial diameter
      of > or = 6 mm. The sensitivity, specificity and accuracy of this criterion were
      84.1%, 94.3% and 89.1%, respectively. There were 3 nodes whose minimal axial
      diameter was < 6 mm in 50 RLNs with central necrosis. Central necrosis combined
      with the minimal axial diameter criteria slightly increased the sensitivity at a
      stable specificity. CONCLUSION: The reasonable radiologic criteria for assessing
      RLN metastasis of NPC are: (1) node with a minimal axial diameter > or = 6 mm;
      and (2) any node with central necrosis.

PMID- 16796888
TI  - [Mechanism of signal transduction of differentiation of mesenchymal stem cells
      into cytokeratin-expressing epidermoid cells].
AB  - OBJECTIVE: To investigate the role of the signal routes P38, ERK, and Rho in the
      differentiation of bone marrow mesenchymal stem cells (MSCs) into epidermoid
      cells. METHODS: (1) MSCs were separated from the bone marrow of Wistar rats by
      Ficoll-Pague lymphocyte separating medium and proliferated in culture medium.
      Then the MSCs were immunocytochemically stained to detect the expression of
      surface antigens. (2) The MSCs were randomly divided into 3 groups: control
      group; pure induction induced group, cultured with epithelial growth factor (EGF)
      added into the culture fluid, and Rho inhibition group, cultured with EGF and
      HA1077, a ROK inhibitor, added into the culture fluid. One, 3, 5, and 7 days
      later FC was used to detect the levels of phosphorylated P38 and ERK. (3) MSCs
      were randomly divided into 4 groups: control group, cultured with low-sugar DMEM
      complete culture fluid; pure induction group, cultured with supernatant of rat
      fibroblasts and EGF added into the culture fluid, p38 blocking group, with
      SB203580, inhibitor of P38 added into the culture fluid; and ERK blocking group,
      with PD98059, inhibitor of ERK added into the culture fluid. Seven days later, SP
      method was used to detect the expression of CK5/8 and CK19 induced by MSCs. (4)
      MSCs were randomly divided into 4 groups: control group; pure induction group,
      with supernatant of rat fibroblasts and EGF added into the culture fluid; and RHO
      blocking group, with HA1007 added into the culture fluid. Seven days later, FC
      was used to detect the expression of CK5/8 and CK19. RESULTS: (1) Both FC and
      immunocytochemistry showed that the MSCs were uniformly positive in CD29 and
      CD44, but did not express CD34 and CD45. (2) The phosphorylated P38 rate remained
      0.01% in the control group. The phosphorylated P38 rate was 0.04%, significantly
      higher than that of the control group (0.01%, P < 0.05) at day 5, and then
      lowered to 0.01% at day 5 in the pure induction group; and became 6.17%, 4.13%,
      3.97%, and 0.41% respectively at day 1, 3, 5, and 7, all significantly higher
      than those of the control group (all P < 0.05), in the Rho inhibition group. The
      phosphorylated ERK level was 4.23% in the control group; became 0.39% and 0.40%
      at day 3 and day 5 (both P < 0.05), and then returned to 5.10% at day 7 in the
      pure induction group; and was not significantly changed at days 1, 3, and 5, and
      then became 0.41%, significantly lower than that of the control group (P < 0.05),
      in the Rho blocking group, (3) The control group was CK5/8 and CK19 negative. The
      CK5/8 and CK19 rates at day 7 of the pure induction group were 3.01% and 6.47%
      respectively, both significantly higher than those of the p38 inhibition group
      (1.43% and 5.41% respectively, both P < 0.05). The CK5/8 and CK19 expression
      rates of the ERK inhibition group were 5.54% and 7.56% respectively, both
      significantly higher than those of the pure induction group (both P < 0.05), (4)
      The CK5/8 and CK19 expression rates of the HA1077 group were 21.65% and 39.41%
      pure, both significantly higher than those of the pure induction group (1.81% and
      10.19% respectively, both P < 0.05). CONCLUSION: p38 route may play an active
      role in the differentiation of MSCs into epidermoid cells. Blocking of the
      upstream signal Rho may enhance the activation of p38 route and then promote the
      differentiation of MSCs into epidermoid cells.

PMID- 16796889
TI  - [Effect of chronic mild and moderate iodine excess on thyroid anti-oxidative
      ability of iodine deficiency and non-iodine deficiency Wistar rats].
AB  - OBJECTIVE: To investigate the effects of chronic mild and moderate iodine excess
      on thyroid oxidative injury and anti-oxidative ability of iodine deficiency and
      non-iodine deficiency Wistar rats. METHODS: Four-week-old Wistar rats were fed
      with iodine deficient diet for three months to make iodine deficient goiter
      models, then divided randomly into three groups: iodine deficient control group
      (Group IDC) fed with double distilled water, iodine-supplement group I (Group IS
      I) fed with potassium iodate solutions with the iodine concentrations of 100
      microg/L, and iodine-supplement group II (Group IS II), fed with potassium iodate
      solution with the iodine concentrations of 330 microg/L. Another four-week-old
      Wistar rats were fed with normal diet for three months, and then divided randomly
      into three groups: normal control group (NC) fed with double distilled water,
      iodine-excess group I (IEI) fed with potassium iodate solution with the iodine
      concentration of 300 microg/L, and iodine-excess group II (Group IEII), fed with
      potassium iodate solution with the iodine concentration of 660 microg/L. 1, 2, 4,
      8, and 24 weeks after treatment samples of urine were collected to detect the
      median urine iodine (MUI), samples of plasma were collected from the hearts of 8
      14 rats from each group and then rats were killed. Their thyroid glands were
      taken out to measure the wet weight and made into homogenate. Biochemical method
      was used to measure the activities of glutathione-peroxidase (GSH-P(X)) and
      superoxide dismutase (SOD) as well as the contents of malonyldialdehyde (MDA) and
      H2O2 in the homogenates of thyroid glands. RESULTS: The GSH-P(X) activity 2 weeks
      after treatment of Group IS II was significantly lower than that of Group IDC (P
      < 0.05), and the GSH-P(X) activity 4 weeks after treatment of Group IS I was
      significantly lower than that of Group IDC (P < 0.001). The activities of GSH
      P(X) 4, 8, and 24 weeks after treatment of Groups IS I and IS II were all lower
      than those of Group C at the same time points significantly (P < 0.001, < 0.01,
      and < 0.05 respectively). The activities of SOD were decreased gradually in
      Groups IS I and IS II and were significantly lower than those of Group IDC since
      8 weeks after treatment (P < 0.001 or < 0.05). The SOD activities in thyroid
      glands of Groups IEI and IEII since 8 weeks after treatment decreased
      significantly in comparison with Group NC (all P < 0.01 or < 0.001). The contents
      of H2O2 in thyroid glands of Groups IS I and IS II were significantly lower than
      those of Group IDC at different time points (P < 0.001, < 0.01, or < 0.05), and
      were significantly lower than those of Group NC 8 and 24 weeks after treatment (P
      < 0.001 or < 0.01). The contents of MDA in thyroid glands since 2 weeks after
      treatment of Group IEI were all significantly lower than those of Group IDC at
      the same time points (all P < 0.05), and the content of MDA in thyroid glands
      since 1 week after treatment of Groups IS II were all significantly lower than
      those of Group IDC at the same time points (all P < 0.05). CONCLUSION:
      Supplementation of 100 microg/L and 330 microg/L iodine on iodine deficiency
      Wistar rats may alleviate the oxidative injury but weaken the anti-oxidative
      protection of thyroid. The anti-oxidative protection of thyroid glands of non
      iodine deficiency Wistar rats may also be weakened by supplementation of 300
      microg/L and 660 microg/L iodine.

PMID- 16796890
TI  - [Therapeutic effects of insulin-sensitizing drugs on nonalcoholic fatty liver
      disease: experiment with rats].
AB  - OBJECTIVE: To investigate the therapeutic effects of insulin-sensitizing drugs,
      rosiglitazone and metformin, on nonalcoholic fatty liver disease (NAFLD).
      METHODS: Forty-four male SD rats were randomized into 4 groups: normal control
      group (n = 8, fed with normal food) and NAFLD rats (n = 36, fed with high-fat
      food). Eight weeks later 4 rats were randomly selected from the NAFLD group and
      were killed to undergo pathological examination of the liver. When the
      establishment of experimental model of NAFLD rats was confirmed the remaining 32
      NAFLD rats were subdivided into 4 equal subgroups: NAFLD control group (to be fed
      continuously with high-fat food), rosiglitazone treatment group (fed with normal
      food and rosiglitazone 1.5 mg x kg(-1) x d(-1) by gastric perfusion), metformin
      treatment group (fed with normal food and metformin 150 mg x kg(-1) x d(-1) by
      gastric perfusion), and dietary treatment group (fed with normal food and normal
      saline by gastric perfusion). By the end of the 12th week, all rats were killed
      to isolate the samples of serum to test the levels of total cholesterol (TC),
      triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and
      tumor necrosis factor-alpha (TNF-alpha). Samples of liver tissue were taken to
      undergo pathology to examine fatty degeneration and inflammatory cell
      infiltration and detection of the levels of TC and TG. In the liver the weights
      of body and liver were measured so as to calculate the liver index. RESULTS: (1)
      The levels of serum TC, TG, ALT, and AST, liver TC and TG, and liver index of the
      NAFLD control group increased significantly, and the liver histology of the NAFLD
      control group expressed moderate to severe fatty degeneration. (2) The serum TC
      levels of the rosiglitazone and metformin groups were 2.49 mmol/L +/- 0.68 mmol/L
      and 2.49 mmol/L +/- 0.58 mmol/L, both significantly lower than that of the NAFLD
      control group (4.55 mmol/L +/- 1.58 mmol/L, both P < 0.001). The serum TG levels
      of the rosiglitazone and metformin groups were 0.61 mmol/L +/- 0.17 mmol/L and
      0.63 mmol/L +/- 0.16 mmol/L respectively, both significantly lower than that of
      the NAFLD control group (0.85 mmol/L +/- 0.15 mmol/L, both P < 0.001). The serum
      level of ALT of the rosiglitazone and metformin groups were 38.3 U/L +/- 10.6 U/L
      and 43.3 U/L +/- 27.5 U/L respectively, both significantly lower than that of the
      NAFLD control group (110.6 U/L +/- 44.2 U/L, P < 0.001 and P < 0.05). The serum
      levels of AST of the rosiglitazone and metformin groups were 141.7 U/L +/- 14.3
      U/L and 174.5 U/L +/- 57.9 U/L, both significantly lower than that of the NAFLD
      control group (251.8 U/L +/- 91.0 U/L, both P < 0.05). The liver TG levels of the
      rosiglitazone and metformin groups were 18.9 mg/g +/- 2.7 mg/g and 20.4 mg/g +/-
      3.6 mg/g respectively, both significantly lower than that of the NAFLD control
      group (54.8 mg/g +/- 7.6 mg/g, both P < 0.05). The fatty degeneration grades of
      liver tissues of the rosiglitazone and metformin groups were grade: 0.8 +/- 0.3
      and 1.0 +/- 0.2, both significantly lower than that of the NAFLD control group
      (grade 2.8 +/- 0.5, both P < 0.05). The hepatic inflammation scores of: the
      rosiglitazone and metformin groups were 0.8 +/- 0.2 and 1.0 +/- 0.3 respectively,
      both significantly lower than that of the NAFLD control group (1.8 +/- 0.4, both
      P < 0.05). The levels of abnormality in serum TC and TG, liver TG, and liver
      histology of the dietary treatment group were all alleviated in comparison with
      the NAFLD control group, but were somewhat severer than those of the
      rosiglitazone and metformin treatment groups. (3) The serum TNF-alpha levels of
      the rosiglitazone and metformin treatment groups were 124.6 pg/mL +/- 21.0 pg/mL,
      154.9 pg/mL +/- 32.5 pg/mL respectively, both significantly lower than that of
      the NAFLD group (324.2 pg/mL +/- 34.2 pg/mL, P < 0.001 and P < 0.05). The liver
      TNF-alpha levels of the rosiglitazone and metformin treatment groups were 0.24 +/
      0.14 and 0.30 +/- 0.12 respectively, both significantly lower than that of the
      NAFLD group (0.85 +/- 0.12, both P < 0.001). The levels of FAS mRNA expression of
      the rosiglitazone and metformin treatment groups were 0.22 +/- 0.14 and 0.29 +/-
      0.16 respectively, both significantly lower than that of the NAFLD group (0.68 +/
      0.23, P < 0.001 and P < 0.005). CONCLUSION: The insulin-sensitizing drugs,
      rosiglitazone and metformin, are effective in the treatment of NAFLD.

PMID- 16796891
TI  - [Therapeutic effects of pravastatin on colitis induced by acetic acid and
      relevant mechanism: experiment with rats].
AB  - OBJECTIVE: To investigate the therapeutic effects of pravastatin on colitis
      induced by acetic acid and the relevant mechanism. METHODS: 8% solution of acetic
      acid was infusion into the rectum of 50 male SD rats so as to establish models of
      ulcerative colitis induced by acetic acid and 10 rats were used as normal
      controls treated with regular feeding. Then the 50 models of ulcerative colitis
      were randomly assigned into 3 groups: model + placebo group (n = 20, infused
      intragastrically with normal saline 2 ml/d for 7 days), model + pravastatin group
      (n = 15, infused intragastrically with pravastatin 1 mg x kg(-1) x d(-1)), and
      model + salicylazosulfapyridium (SASP) group (n = 15, infused intragastrically
      with SASP 0.25 g x kg(-1) x d(-1)). The general conditions, food intake, weight,
      stool consistencies, stool bleeding of rats were observed then the disease
      activity index (DAI) and the therapeutic effects were evaluated. All the rats
      were sacrificed at day 8 with their colons taken out. The colon length, colon
      mucosa damage index (CMDI), and histological score were evaluated and nitric
      oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) of the tissue
      were measured as well. RESULTS: Compared with those of the model + placebo and
      model + SASP groups, the colon length, DAI, CMDI, and histological score of the
      model + pravastatin group were significantly improved (all P < 0.05), the levels
      of NO and MDA were significantly reduced, while the SOD level was increased
      remarkably (both P < 0.05). CONCLUSION: Pravastatin may ameliorate the colitis by
      antioxidant activity. Its therapeutic effect is more obvious than the
      conventional medicine SASP.

PMID- 16796895
TI  - [Evaluation of the efficacy of phenobarbital in treatment of epilepsy in rural
      areas: study of 2455 patients in rural China].
AB  - OBJECTIVE: To evaluate the efficacy of phenobarbital in treatment of patients
      with convulsive forms of epilepsy in rural areas and to develop a suitable
      relevant model for rural China. METHODS: A demonstration protocol was conducted
      in the rural areas of 8 counties from 6 provinces and municipality in China,
      Heilongjiang, Ningxia, Henan, Jiangsu, Shanxi, and Shanghai from December 2001 to
      June 2004. Epidemiological investigation of the prevalence and treatment gap of
      epilepsy was carried out. Patients with convulsive forms of epilepsy thus
      screened underwent treatment of phenobarbital. Physicians of township hospitals
      received short-term training to be in charge of the treatment and regular follow
      up of the patients. RESULTS: A total of 2455 patients with generalized tonic
      clonic seizures in these 6 rural areas were screened and entered the treatment
      group. 347 patients (26.2%) had been seizure-free during the period of these 2
      years, 415 patients (31.3%) had their seizure frequencies decreased by > 75% as
      compared with those during the period of 6 months before treatment, and the
      conditions of 26.1% of the patients did not change or even became worse. About
      26.1% of the patients had mild side effects, 3.7% had moderate side effects, and
      only 0.3% had severe side effects when the dosage of phenobarbital in the first 3
      months was increased. 597 patients (24.3%) withdrew from the treatment group
      because of various reasons. CONCLUSION: This protocol was suitable to the rural
      areas of China. The trained physicians are capable of fulfilling the task to
      treat the patients with epilepsy. Phenobarbital is an effective drug for most
      patients with convulsive seizures and has no severe side effect.

PMID- 16796896
TI  - [Application of diffusion tensor imaging fractography in minimally invasive
      surgery of brain tumors].
AB  - OBJECTIVE: To investigate the effects and prospect of application of diffusion
      tensor imaging (DTI) fractography in minimally invasive surgery of brain tumors.
      METHODS: DTI fractography was performed in 52 patients with malignant brain
      tumors. Based on the DTI fractography results, 34 of the 52 patients underwent
      operation under neuro-navigation, and 18 of the 52 patients underwent operation
      routine minimally invasive craniotomy and tumor resection without neuro
      navigation. RESULTS: The rate of total tumor resection was 86.5% (45/52). The
      mortality was 1.9% (1/52). The disability rate was 11.5% (6/52). No case needed
      the second operation. CONCLUSION: DTI fractography has raised the minimally
      invasive neurosurgery to the level of protecting the nuclei and nerve tracts and
      guiding intra-operative management of infiltration of deep-seated tumors,
      especially when combined with neuro-navigation and interventional MRI.

PMID- 16796897
TI  - [Characteristics of recurrence of T1G3 transitional cell carcinoma of bladder].
AB  - OBJECTIVE: To investigate the characteristics of recurrence of T1G3 transitional
      cell carcinoma (TCC) of bladder. METHODS: The clinical data of 72 patients with
      TCC of bladder of the stage T1, 37 being of the stage T1G3 and 35 being of the
      stage T1G1-2, who underwent the initial treatment by transurethral resection of
      bladder tumor plus post-operative bladder infusion were analyzed. RESULTS: The
      first, second, third, and fourth year recurrent rates of the T1G3 group were
      29.7%, 40.5%, 18.9%, and 10.8% respectively, all significantly higher than those
      of the T1G2 group (14.3%, 34.3%, 31.4%, and 20.0% respectively, t = 1.994, P =
      0.025). The rate of recurrence for only time was 10.8% in the T1G3 group (4/37),
      significantly lower than that of the T1G1-2 group (17/35, 48.6%, P < 0.01). The
      rate of recurrence for more than 3 times was 54.0% in the T1G3 group (20/37),
      significantly higher than that of the T1G1-2 group (6/35, 17.2%, P < 0.01). The
      rate of recurrent tumor at the pathological stage over T2 was 86.5% (32/37) in
      the T1G3 group, higher than that of the T1G1-2 group (42.8%, 15/35). The rate of
      partial or total cystectomy at the last recurrence in the T1G3 group was 94.6%
      (35/37), significantly higher than that of the T1G1-2 group (57.1%, 20/35, chi(2)
      = 14.00, P < 0.05). CONCLUSION: A kind of dangerous bladder cancer, TCC at the
      stage T1G3 is apt recur soon after the treatment with a high recurrent frequency.
      Most recurrent tumors evolve into invasive cancer.

PMID- 16796898
TI  - [Intra-operative fluoroscopy for detecting pedicle screw violation in lumbar
      vertebrae by guided pin axial position].
AB  - OBJECTIVES: To develop an applicable and accurate intra-operative fluoroscopical
      angle to observe the placement of pedicle screw and pedicle violation. METHODS:
      Lateral radiographs were taken on eighty lumbar pedicles in eight cadaveric
      vertebral specimens to measure the sagittal pedicle angles. The pedicles of the
      vertebral arch were scanned by computed tomography (CT) to measure the transverse
      pedicle angles. Guided pins and pedicle screws were inserted by awl into the
      pedicles through the holes drilled in the lumbar pedicles so as to establish 3
      types of model: medial violation (n = 29), lateral violation (n = 25), and
      properly placed screw (n = 26) the anterior and posterior portions of the lumbar
      pedicle cortex could be identified by the fluoroscopy C-arm. Fluoroscopy with the
      aid of C-arm was taken on each pedicle in five different directions: lateral
      position; anteroposterior position; pedicle axial position; guided pin axial
      position; and pedicle screw axial position. The positions of guided pin and
      pedicle screw were evaluated. The gold standard was acquired by excising the
      vertebral plate and observing directly. RESULTS: Nine cases of medial violation
      were discovered and the accuracy rate was 33.75% by anteroposterior fluoroscopy.
      The accuracy rate was 95% by the pedicle axial fluoroscopes, including 4 cases of
      medial inclination but properly placed screws were mistaken for medial violation
      by pedicle axial fluoroscope. The accuracy rate was 100% by guided pin axial
      position fluoroscopy, including 29 cases of medial violations, 25 cases of
      lateral violation, and 26 cases of properly placed screws. CONCLUSION: The
      approach of intra-operative fluoroscopy of guided pin axial position is a
      reliable technology for detecting pedicle violation with the aid of C-arm. The
      incidence of flexible pedicle screw from human factors can be reduced.

PMID- 16796899
TI  - [Relationship between polymorphisms of plasminogen activator inhibitor-1 promoter
      gene and pulmonary thromboembolism in Chinese Han population].
AB  - OBJECTIVE: To determine the prevalence of polymorphisms in the plasminogen
      activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphisms in Chinese Han
      population and to investigate whether they are associated with pulmonary
      thromboembolism (PTE). METHODS: Samples of peripheral venous blood were collected
      from 101 patients with PTE diagnosed by high probability of lung
      ventilation/perfusion scan and/or multi-slice CT pulmonary angiography (CTPA) as
      well as medical history and clinical manifestations, 67 males and 34 females,
      aged 48 +/- 15, and 101 age and sex-matched healthy controls from the same
      geographic area as controls. The genome DNA was extracted from the whole blood
      using potassium iodide-phenol-chloroform method. Polymerase chain reaction (PCR),
      denaturing high performance liquid chromatography (DHPLC), and sequence analysis
      were used to screen the single nucleotide polymorphisms and the genotype
      distribution of -675 4G/5G located in the promoter region of the PAI-1 gene.
      RESULTS: The frequencies of the allele 4G of PAI-1 gene in the controls were
      0.495, significantly lower than in the PTE patients (0.733, chi(2) = 24.060, P <
      0.01). The frequencies of the allele 5G of PAI-1 gene in the controls were 0.505,
      significantly higher than that in the PET patients. The genotype frequency of
      4G4G of the PET patients was 57.4%, significantly higher than that of the
      controls (30.7%, P = 0.000). The genotype frequencies of 4G5G and 5G5G of the PET
      patients were 31.7% and 10.9% respectively, not significantly different from
      those of the controls (37.6 and 31.7% respectively). The presence of 4G allele of
      PAI-1 gene was found to be a greater risk factor for PTE. In comparison with the
      controls, the OR of 4G4G + 4G5G, 4G4G, and 4G5G in the PET patients were 3.794
      (1.786 - 8.060), 5.443 (2.416 - 12.260), and 2.450 (1.067 - 5.623) respectively
      with the P values of 0.001, 0.000, and 0.035 respectively. CONCLUSION: The 4G/5G
      and 4G/4G genotypes are associated with the pathogenesis of PET.T.

PMID- 16796901
TI  - [Inhibition of rat RAW264.7 macrophage inflammatory cytokines release by small
      hairpin RNAi targeting Toll-like receptor].
AB  - OBJECTIVE: To construct a eukaryotic expression vector carrying the small hairpin
      RNA (shRNA) for Toll-like receptor 4 (TLR4) mRNA and a reporter gene of enhanced
      green fluorescence protein (EGFP) and study the inhibition of cytokine release by
      rat RAW264.7 macrophages induced by lipopolysaccharide (LPS) stimulation through
      transfection and expression of shRNA targeting TLR4 gene via the RNAi mechanism.
      METHODS: The H1 promotor and double BbsIrestrict endoenzyme site from the plasmid
      psiRNA-hH1neo were cloned into the reporter gene plasmid pEGFP-C1 at the
      MluIrestrict endoenzymic site, thus forming the plasmid pEGFP-H1/siRNA containing
      Bbs site and reporter EGFP gene. Then an oligo nuclear hairpin sequence targeting
      TLR4 gene was designed by the internet tool siRNA Wizard and then inserted into
      the plasmid pEGFP-H1/siRNA so as to form the plasmid pEGFP-H1/TLR4-siRNA. Rat
      macrophages of the line RAW264.7 were cultured and transfected with pEGFP-H1/TLR4
      siRNA mediated by lipofectamine 2000. Another RAW264.7 cells were transfected
      with pEGFP-H1/control sequence-siRNA or blank plasmid. Lipopolysaccharide was
      added into the 3 kinds of culture fluid for 2 and 68 hours respectively. ELSA was
      used to detect the levels of tumor necrosis factor-alpha (TNF-alpha) in the
      supernatants. RESULTS: Restriction endonuclease analysis showed that the
      construction pEGFP-H1/TLR4-siRNA carrying hairpin RNA for TLR4 gene and reporter
      EGFP gene was successful. The expression of EGFP gene was 50% +/- 8%. The TNF
      alpha level of the TLR4-siRNA transfection group 2 hours and after transfection
      was 825 pg/ml +/- 136 pg/ml, significantly lower than those of the pEGFP
      H1/control sequence-siRNA and blank plasmid groups (2190 pg/ml +/- 359 pg/ml and
      1265 pg/ml +/- 283 pg/ml respectively, both P < 0.01). The TNF-alpha level of the
      TLR4-siRNA transfection group 8 hours and after transfection was 1179 pg/ml +/-
      240 pg/ml, significantly lower than those of the pEGFP-H1/control sequence-siRNA
      and blank plasmid groups (4720 pg/ml +/- 227 pg/ml and 4689 pg/ml +/- 310 pg/ml
      respectively, both P < 0.01). CONCLUSION: shRNA targeting TLR4 gene can inhibit
      the TNF-alpha release by RAW264.7 cells evoked by LPS.

PMID- 16796900
TI  - [Large-scale screening of mtDNA A1555G mutation in China and its significance in
      prevention of aminoglycoside antibiotic induced deafness].
AB  - OBJECTIVE: To explore the necessity of large-scale screening of mtDNA A1555G
      mutation in prevention of aminoglycoside antibiotic induced deafness (AAID) and
      to develop a feasible method to prevent AAID. METHODS: A total of 1836 patients
      with non-syndromic hearing impairment (NSHI), 1352 students of schools for deaf
      mutes in 11 provinces and municipality in China, 413 out-patients, and 71 persons
      from the families with maternal relatives suffering from AAID, underwent
      questionnaire survey and/or PCR for A-to-G mutation at nucleotide 1555 of the
      mitochondrial genome. RESULTS: Sixty three patients with mtDNA A1555G mutation
      were found among the 1836 NSHI patients. Fifty-two maternal pedigrees were
      identified. 536 cases with normal hearing from these pedigrees were informed to
      avoid using aminoglycoside antibiotics (AmAn). CONCLUSION: Large-scale screening
      of mtDNA A1555G mutation and relevant health education to avoid use of AmAn are
      effective to prevent ototoxicity in the A1555G carriers and their maternal
      relatives.

PMID- 16796902
TI  - [Impact of hydrogen sulfide, a novel gaseous signal molecule on nitric
      oxide/nitric oxide synthase pathway in left-to-right shunt: experiment with
      rats].
AB  - OBJECTIVE: To explore the impact of endogenous hydrogen sulfide (H(2)S), a novel
      gaseous signal molecule, on the nitric oxide (NO)/nitric oxide synthase (NOS)
      pathway in left-to-right shunt. METHODS: Thirty-two male SD rats were randomly
      divided into 4 equal groups: shunt group undergoing abdominal aorta-inferior vena
      cava puncture so as to establish model of left-to-right shunt; shunt + PPG group
      undergoing abdominal aorta-inferior vena cava puncture so as to establish model
      of left-to-right shunt and then intraperitoneal injection of propargylglycine
      (PPG), an inhibitor of cystathionine-gamma-lyase: sham group undergoing sham
      operation; and sham + PPG group undergoing sham operation and then
      intraperitoneal injection of PPG. Four weeks later, right cardiac catheterization
      was conducted to measure the mean pulmonary artery pressure (MPAP). Then the rats
      were killed and their lung tissues and samples of plasma were collected. The
      contents of H(2)S, nitric oxide (NO), and nitrogen oxide synthase (NOS) activity,
      and the content of plasma NO were calculated. Western blotting was used to detect
      the endothelial nitric oxide synthase (eNOS) protein in the lung tissues. The
      correlation of MPAP with lung H(2)S and NO was analyzed. RESULTS: The MPAP of the
      shunt group was not significantly different from that of the sham group, and the
      MPAP of the shunt + PPG group was significantly higher then those of the shunt
      group and sham group by 15.82% and 20.55% respectively (both P < 0.05). The
      content of lung tissue H(2)S of the shunt group was 37.56 +/- 2.13 micromol/mg,
      significantly higher than that of the shunt group (14.35 +/- 1.76, P < 0.05), the
      content of lung tissue H(2)S of the shunt + PPG group was 28.76 +/- 2.24
      micromol/mg, significantly lower than that of the shunt group (P < 0.05). The
      lung tissue NO content of the shunt group was 38.48 micro +/- 6.53
      micromol/microg, significantly higher than that of the sham group (31.78 +/- 6.51
      micromol/microg). The NOS activity of the shunt group was 15.12 +/- 2.44 U/mg
      protein, significantly higher than that of the sham group (12.00 +/- 1.40 U/mg
      protein, P < 0.05). The lung eNOS content of the shunt group was significantly
      higher than that of the sham group (P < 0.05). The plasma NO content of the shunt
      group was 23.18 +/- 3.56 micromol/L, significantly higher than that of the sham
      group (17.94 +/- 3.39 micromol/L, P < 0.05). The lung tissues NO and NOS
      activity, and plasma NO of the shunt + PPG group were 46.04 +/- 5.95
      micromol/microg, 20.89 +/- 3.94 U/mg protein, and 27.79 +/- 4.82 micromol/L
      respectively, all significantly higher than those of the shunt group (38.48 +/-
      6.53 micromol/microg, 15.12 +/- 2.44 U/mg protein, and 23.18 +/- 3.56 micromol/L,
      all P < 0.05). The eNOS content of the shunt + PPG group was significantly higher
      than that of the shunt group (P < 0.05). The lung H(2)S content was negatively
      correlated with the MPAP and lung NO content (r = -0.705, P = 0.005; and r = 
      0.645, P = 0.013). CONCLUSION: Endogenous H(2)S may play a regulatory role in the
      pulmonary artery pressure of left-to-right shunt through inhibiting NO/NOS
      pathway.

PMID- 16796904
TI  - [Electrophysiological effects of hyperpolarization activated cyclic nucleotide
      gated channel 4 overexpression in neonatal cardiomyocytes mediated by recombinant
      adenovirus].
AB  - OBJECTIVE: To explore the electrophysiological effects of hyperpolarization
      activated cyclic nucleotide gated channel 4 (HCN4) overexpression in rat neonatal
      cardiomyocytes mediated by recombinant adenovirus. METHODS: Ventricular
      cardiomyocytes were obtained from 20 neonatal rats. Recombinant adenovirus
      carrying HCN4 gene, AdHCN4, a dominant isoform of hyperpolarization activated
      cyclic nucleotide gated cation channel gene in cardiac transduction system, was
      constructed and used to transfect the neonatal rat ventricular cardiomyocytes.
      Untransfected cardiomyocytes were used as controls. RT-PCR and immunofluorescence
      cytochemistry were used to detect the HCN4 mRNA and protein expression. The
      electrophysiological characteristics of infected cardiomyocytes were studied by
      patch clamp. RESULTS: The mRNA and protein expression levels of HCN4 in AdHCN4
      infected cardiomyocytes were both markedly higher than those of the control
      cardiomyocytes. AdHCN4 caused a significant increase in The spontaneous rate in
      the transfected cardiomyocytes was 92.5 + 7.4 bpm, significantly higher than that
      of the control cells (68.9 + 6.2 bpm, P < 0.05). Patch clamp experiments showed
      that the pacemaker current density in the AdHCN4 infected cardiomyocytes was
      115.7 + 7.8 pA/pF, significantly higher than that of the untransfected cells (7.2
      + 0.6 pA/pF, P < 0.05). CONCLUSION: Overexpression of HCN4 can enhance the
      autorhythmicity of neonatal cardiomyocytes and significantly increase the
      spontaneous beat rate. HCN4 channel gene may represent a candidate gene in gene
      therapy for bradycardia diseases.

PMID- 16796905
TI  - [Association of single nucleotide polymorphism of megsin gene with IgA
      nephropathy].
AB  - OBJECTIVE: To investigate whether the single nucleotide polymorphisms (SNPs) in
      the gene of megsin, a novel serine protease inhibitor, account for the
      pathogenicity of IgA nephropathy (IgAN). METHODS: A comprehensive megsin gene
      survey, including the entire coding region, part of the regulatory region, and
      exon-intron connection region, was performed by PCR-direct sequencing on the DNA
      samples of peripheral blood from 12 randomly selected IgAN patients and 12
      randomly selected healthy persons. Eight SNPs with moderate or high frequencies
      (with the frequency > 5%) selected from the 11 SNPs found were used as candidate
      SNPs. Then 210 IgAN patients proven by renal-biopsy, all of Chinese Han
      nationality, and 103 normal volunteers were recruited. The 8 candidate SNPs were
      genotyped by direct sequencing or PCR-RFLP and a case-control association study
      was carried out. RESULTS: The SNP of 267G/A in 5'untranslated region within exon1
      was significantly associated with IgAN. The frequency of AG/AA genotype of the
      IgA patients was 29.0%, significantly higher than that of the controls (16.5%, P
      < 0.05). The frequency of A allele of the IgA patients was 14.8%, significantly
      higher than that of the controls (8.7%, P < 0.05). The odds ratio of AG/AA
      genotype versus GG genotype was 2.07 with the 95% confidence interval of 1.15 -
      3.74. The linkage disequilibrium between two SNPs existed commonly within one
      gene. CONCLUSION: 267G/A in megsin gene is associated with IgAN susceptibility.
      AG and AA genotypes are the risk factors of pathogenesis of IgAN.

PMID- 16796906
TI  - [Therapeutic effect of brain-specific angiogenesis inhibitor 1 on glioblastoma:
      an animal experiment].
AB  - OBJECTIVE: To study the therapeutic effects of brain-specific angiogenesis
      inhibitor 1 (BAI1) on human glioblastoma and relevant mechanism. METHODS:
      Recombinant adenovirus carrying human BAI1 cDNA, AdeBAI1 and recombinant
      adenovirus carrying LacZ, AdeMock, were constructed with the COS-TPC method. The
      successful construction of AdeBAI1 and expression of AdeBAI1 was verified using
      RT-PCR. Glioblastoma cells of the line U87MG were transplanted into the mice
      brain using stereotactic technique. AdeBAI1 and AdeMock were injected into the
      tumors after the tumors were developed. The survival of the mice was observed.
      Human glioblastoma cells of the lines SW1783, U87MG, and U373MG were cultured and
      transfected with AdeBAI1 or AdeMock, and then collected 48 hours later and
      counted using MTT method. The total RNA was extracted using Trizol agent. The
      mRNA of BAI1 and other angiogenesis related genes were detected using RT-PCR.
      RESULTS: The mean survival time of the AdBAI1-treated mice was 26 +/- 4.6 d,
      significantly longer than that of the AdMock-treated mice (17.3 +/- 2.3 d, P <
      0.05). RT-PCR showed that BAI1 mRNA was expressed only in the glioblastoma cells
      transfected with AdeBAI1. The number of AdeBAI1 treated glioblastoma cells was
      2.12 +/- 0.18 x 10(5), significantly less than that of the AdeMock treated cells
      (4.23 +/- 0.18 x 10(5), P < 0.05). The mRNA expression of angiostatin of the
      AdeBAI1 treated cells was 0.66 +/- 0.08, significantly less than that of the
      AdMock-treated cells (0.95 +/- 0.12, P < 0.05). The mRNA expression of vascular
      endothelial growth factor (VEGF) of the AdeBAI1 treated cells was 0.68 +/- 0.07,
      significantly less than that of the AdMock-treated cells (1.02 +/- 0.14, P <
      0.05). The mRNA expression of VEGF-B of the AdeBAI1 treated cells was 1.11 +/-
      0.10, significantly more than that of the AdMock-treated cells (0.77 +/- 0.18, P
      < 0.05). The mRNA expression of thrombospondin of the AdeBAI1 treated cells was
      1.16 +/- 0.16, significantly more than that of the AdMock-treated cells (0.60 +/-
      0.22, P < 0.05). CONCLUSION: Intratumor injection of AdeBAI1 can inhibit the
      tumor growth. The anti-tumor effect of BAI1 may arise from both anti-angiogenesis
      and anti-proliferation effects.

PMID- 16796916
TI  - [Strengthening the elementary research on reproductive medicine].

PMID- 16796917
TI  - [Isolation, purification and immunochemical characteristics of spermatogonia of
      rat].
AB  - OBJECTIVE: To explore the approach of isolation and purification of spermatogonia
      and its immunochemical characteristics. METHODS: Compound enzymatic digestions
      were used to prepare germ cell suspensions of Sprague-Dawley rats aged 10 days,
      and velocity sedimentation and discontinuous Percoll density gradient
      centrifugation were used to isolate and purify the spermatogonia. Using c-kit and
      alpha(6)-integrin multiclone antibodies as markers respectively, the
      immunochemical characteristics of the spermatogonia in the testicular tissue were
      observed and the c-kit and alpha(6)-integrin expression rates of the purified
      cells were detected by flow cytometry. RESULTS: The spermatogonia uniquely
      expressed c-kit and alpha(6)-Integrin in the testicular tissue. C-kit and
      alpha(6)-integrin were positively expressed in the purified cell suspensions.
      Using c-kit as the cell marker, the positive rate was 1.59% +/- 0.04% in the
      unpurified group, significantly lower than that of the purified group (68.33% +/-
      2.45%, P < 0.01). Using alpha(6)-integrin as the cell marker, the positive rate
      of the unpurified group was 2.38% +/- 0.60%, significantly lower than that of the
      purified group (72.04% +/- 3.65%, P < 0.01). Trypan blue staining showed that the
      cell viability of the purified cell suspensions was more than 95%. CONCLUSION: c
      kit and alpha(6)-integrin can be used as the molecular markers of spermatogonium
      at special stage. Spermatogonia with high purity and viability can be obtained
      via the steps including digestions with enzymes, velocity sedimentation and
      discontinuous percoll density gradient centrifugation.

PMID- 16796918
TI  - [Detection of Y chromosome microdeletions in patients with severe oligozoospermia
      and azoospermia].
AB  - OBJECTIVE: To explore the clinical significance of azoospermia factor (AZF)
      region deletion. METHODS: Detection of the Y-link sequence tagged sites in AZF
      region was conducted by means of 2 multiplex polymerase chain reactions among 80
      patients with severe oligozoospermia and 63 patients with azoospermia, totally
      143. RESULTS: Twenty-one cases of microdeletion were found among the 143
      infertile patients with a prevalence of 14.7%. PCR analysis showed that deletion
      of the portions of Yq in 12 of the 62 idiopathic infertility patients, 3 being
      with severe oligozoospermia and 9 with azoospermia, and in 9 out of the 81
      patients with non-idiopathic infertility. PCR analysis of 40 normal fertile men
      did not detect any abnormality. The results of the microdeletion showed that 1
      patient had a microdeletion in the AZFa region with sY84 and sY86 (1/21, 4.8%), 2
      patients presented a large deletion involving sY127 and sY143 from AZFb, and
      sY254 and sY255 from AZFc (1/21, 9.5%). Two patients had the deletions located in
      AZFb region (2/21, 9.5%), and 16 patients had a deletion on the AZFc region
      involving the DAZ (deleted in azoospermia) gene (16/21, 76.2%) Among the 21
      infertile men 4 showed a testicular cytologic picture of maturation arrest, 6
      patients had severe hypospermatogenesis, and 11 had Sertoli cell-only syndrome.
      There were not significant differences in location and extent of deletions
      between the patients with idiopathic infertility and those with non-idiopathic
      infertility. CONCLUSION: It is recommended to carry out screening of
      microdeletion of Y chromosome among the patients with idiopathic and non
      idiopathic infertility, especially the candidates for intracytoplasmic sperm
      injection.

PMID- 16796919
TI  - [Changes of nuclear factor-kappa gene binding expression in and apoptosis of
      spermatogenic epithelial cells in the restored testis after torsion: experiment
      with rats].
AB  - OBJECTIVE: To investigate the changes of nuclear factor-kappa gene binding (NF
      kappaB) expression in and apoptosis of spermatogenic epithelial cells in the
      restored testis after torsion and analyze the relationship between them. METHODS:
      Sixteen male SD rats underwent torsion of the left testis clockwise at an angle
      of 720 degrees for 2 hours and then the testis was restored to the original
      position and fixed. Then the 16 rats were randomly divided into 2 equal group:
      Group I in which salicylazosulfapyridium (SASP) suspension was infused intra
      gastrically 5 h after operation and then once a day for 4 times, and Group II in
      which normal saline (NS) was infused in the same manner. Eight rats (Group III)
      underwent sham operation and then infused with NS in the same manner as that of
      Group II. Three days after operation the rats were killed and the samples of the
      testes at the torsion side were taken out and the seminiferous tubules were
      isolated. Western blotting was used to detect the NF-kappaB expression in the
      cytoplasm and nucleus of spermatogenic epithelial cells. Immunohistochemistry was
      used to detect the in situ expression of NF-kappaB. The apoptosis of the
      spermatogenic epithelial cells was examined by TUNEL method. RESULTS: Western
      blotting showed that the NF-kappaB expression in the cytoplasm of spermatogenic
      epithelial cells of Group II was 9.4 +/- 2.68, somewhat lower, but not
      significantly, than those of Group I and III (12 +/- 2.2 and 11.1 +/- 3
      respectively, both P > 0.05). The NF-kappaB expression in the nucleus of
      spermatogenic epithelial cells of Group II was 21.1 +/- 3.6, significantly higher
      than those of Group I and III (8.4 +/- 3.1 and 6.0 +/- 2.3 respectively, both P <
      0.05). However, there were no significant differences in the NF-kappaB expression
      in the cytoplasm and nucleus of spermatogenic epithelial cells between Groups I
      and III. The NF-kappaB activity coefficient of spermatogenic epithelial cells of
      Group II was 2.32 +/- 0.4, significantly higher than those of Groups I and III
      (0.68 +/- 0.3 and 0.52 +/- 0.1 respectively, both P < 0.01). However, there was
      no significant difference in the NF-kappaB activity coefficient of spermatogenic
      epithelial cells between Groups I and III (P > 0.05). The NF-kappaB positive cell
      rate of Group II was 66.1% +/- 3.8%, significantly higher than those of Groups I
      and III (15.6% +/- 2.6% and 10.8% +/- 2.7%, both P < 0.01). The apoptotic cell
      rate of Group II was 37.2% +/- 3.3%, significantly higher than those of Groups I
      and III (7.7% +/- 2.0% and 5.9% +/- 1.7%, both P < 0.01). CONCLUSION: After the
      torsion of testis, NF-kappaB was activated and released from the nucleus into the
      cytoplasm, thus initiating the apoptosis of spermatogenic epithelial cells.

PMID- 16796920
TI  - [Association of baseline cholesterol level and its 10-year change with carotid
      atherosclerosis in the population of Peking University community].
AB  - OBJECTIVE: To explore the association of baseline cholesterol level in 1992 and
      its 10-year change from 1992 to 2002 with the prevalence of carotid
      atherosclerosis. METHODS: In 1992, 1985 subjects of the community of Peking
      University, aged 35 - 64, underwent physical examination and blood-lipid test to
      study the cardio-vascular disease (CVD) risk factors. In 2002, the second survey
      on CVD risk factors was conducted among the existing 1932 subjects, now aged 45 -
      74. In addition, B-mode ultrasonography of the carotid artery was performed too.
      The complete data of 1331 subjects were analyzed. RESULTS: (1) In 2002, the
      prevalence rates of intimal medial thickening (IMT) and carotid plaque in the
      study population were 47.8% and 29.9% respectively. (2) The post-10-year
      prevalence rate of carotid plaque was 19.7% in the subjects with the baseline
      cholesterol < 3.64 mmol/L, and was 46.8% in those with the baseline cholesterol
      6.24 mmol/L, with a thickening rate 3.1 times that of the subjects with the
      baseline cholesterol < 3.64 mmol/L. The higher the baseline TV level, the higher
      the prevalence rates of carotid plaque and IMT. (3) The prevalence rate of
      carotid plaque was 32.0% in the subjects with normal TC in both 1992 and 2002,
      and 50.0% in those with hypercholesterolemia in both 1992 and 2002. CONCLUSION:
      Carotid atherosclerosis is a prevalent disorder in the people aged 45 - 74 in
      Beijing. The prevalence rates of carotid plaque and IMT increase with the
      elevation of baseline cholesterol level.

PMID- 16796921
TI  - [Polymorphic Hind III restriction site of the Y chromosome and essential
      hypertension in Chinese Han People].
AB  - OBJECTIVE: To examine whether there is an association essential hypertension
      pressure and a polymorphic Hind III biallelic marker in the non-recombining
      region of Y chromosome in Chinese Han people. METHODS: Peripheral blood samples
      were collected from 402 males with essential hypertension pressure and 455 age-
      and body height-matched healthy males as control group. Genomic DNA was extracted
      from the white blood cells. Segments of polymorphic Hind III restriction site of
      the Y chromosome were amplified from the genomic DNA by polymerase chain reaction
      (PCR). The PCR products were restricted with 10 U of Hind III overnight at 37
      degrees C. The digested products were subjected to electrophoresis in 3% agarose
      gels, and stained with ethidium bromide. RESULTS: The Hind III (+) genotype was
      found in 58.5% of the men with essential hypertension (235/402), significantly
      lower than that in the healthy men (64.4%, 302/455, P = 0.02). The systolic blood
      pressure of the men with Hind III (+) genotype was 133.8 mm Hg +/- 25.2 mm Hg,
      significantly lower than that of the Hind III (-) genotype (138.0 mm Hg +/- 27.0
      mm Hg, P < 0.05), and the diastolic blood pressure (DBP) of the men with Hind III
      (+) genotype was 83.5 mm Hg +/- 13.3 mm Hg, significantly lower than that of the
      men with Hind III (-) genotype (85.9 mm Hg +/- 14.4 mm Hg, P = 0.01), and the
      mean arterial pressure of the men with Hind III (+) genotype was 100.2 mm Hg +/-
      16.5 mm Hg, significantly lower than that of the of the men with Hind III (+)
      genotype was (103.3 mm Hg +/- 17.6 mm Hg, P = 0.01). CONCLUSION: Polymorphic Hind
      III restriction site of the Y chromosome is associated with essential
      hypertension in Chinese Han people.

PMID- 16796922
TI  - [The effects of nuclear factor-kappaB decoy oligonucleotides on dextran sulphate
      sodium-induced colitis: experiment with mice].
AB  - OBJECTIVE: To investigate the effects of nuclear factor-kappaB (NF-kappaB) decoy
      oligonucleotide (ODN) on dextran sulphate sodium (DSS)-induced colitis. METHODS:
      Nine female BABL/C mice underwent infusion of 0.15 ml normal saline into the
      distant colon and used as controls (Group 1). Twenty-seven female BABL/C mice
      were made into DSS-induced colitis models and then randomly divided into 3
      groups: Group 2 (underwent infusion of 0.15 ml normal saline into the distant
      colon), Group 3 (infused with NF-kappaB decoy ODN 25 nmol solved in 0.15 ml), and
      Group 4 (infused with NF-kappaB scrambled decoy ODN 25 nmol solved in 0.15 ml).
      Disease active index (DAI) was observed every day. Nine days later the mice were
      killed and their colons were taken out to undergo histological examination. The
      tumor necrosis factor (TNF)-alpha level of the colon mucosa was measured by
      enzyme linked immunosorbent assay (ELISA). NF-kappaB expression was determined by
      immunohistochemical staining. The distribution of NF-kappaB decoy ODN was
      investigated by confocal laser microscopy. RESULTS: (1) The DAI scores,
      histological scores and TNF-a level in the colon mucosa of Groups 2 - 4 were all
      significantly higher than those of Group 1 (all P < 0.05). The DAI scores,
      histological scores and TNF-a level in the colon mucosa of Group 3 were all
      significantly lower than those of Groups 2 and 4 (all P < 0.01). (2) In the
      tissue sections NF-kappaB p65 was positive mainly in the nucleus in the 3 DSS
      treated groups without significant differences among these 3 groups, and was
      mainly positive in the cytoplasm in the control group. (3) Confocal laser
      microscopy showed that NF-kappaB decoy ODN could be ingested efficiently into the
      mucosa and submucous layer of colon. (4) There were no significant differences in
      the liver function, kidney function, and blood glucose among all groups.
      CONCLUSION: NF-kappaB pathway is associated with the pathogenesis of DSS-induced
      colitis which is very similar to human UC. Blockade of NF-kappaB pathway by NF
      kappaB decoy ODN shows protective effect on the mice with DSS-induced colitis.

PMID- 16796923
TI  - [Mechanism of inhibiting proliferation of human ovarian cancer cells of the line
      HO-8910 by dexamethasone: the role of RhoB signaling pathway].
AB  - OBJECTIVE: To observe the effect of dexamethasone (Dex) on the proliferation of
      human ovarian cancer cells of the line HO-8910, and explore the role of RhoB
      signaling pathway in this process. METHODS: Human ovarian cancer cells of the
      line HO-8910he were cultured in culture fluids with or without different
      concentrations of Dex. The cell growth levels in anchor-dependent and anchor
      independent manner were detected by MTT and soft agar assay. Another HO-8910
      cells were inoculated in gel with different concentrations of Dex. HO-8910 was
      transfected with the eukaryotic expression plasmid RhoB-wt, blank plasmids pcDNA3
      and RhoB-RNAi, and then the mRNA expression of RhoB, a small GTPase gene, was
      examined by semi-quantitative RT-PCR. and the protein expressions of RhoB, p-Akt,
      and p21(cip1/waf1) and p27, both cyclin kinase inhibitors (CDIs), were detected
      by Western blotting. HO-8910 cells were co-transfected with the reporter gene p21
      luc containing p21 promoter and marker reporter gene pRL-tk-luc, then treated
      with Dex for 24 h. Western blotting was used to detect the transcription of
      p21(cip1/waf1) gene. RESULTS: The RhoB mRNA expression was significantly
      increased 2 hours after the treatment of 100 nM Dex, and peaked 4 hours later as
      high as 2.5 times that of the control group. Western blotting showed that the
      RhoB protein expression increased along the increase of the Des concentration.
      The protein expression of RhoB in the HO-8910 cells transfected with RhoB-wt was
      2.02 times that in the HO-8910 cells transfected with blank plasmid, and the
      protein expression of RhoB in the HO-8910 cells transfected with RhoB-RNAi was
      36% of that of the blank plasmid group (P < 0.01). The HO-8910 cell proliferation
      of the RhoB-RNA1 group was not significantly different from that of the control
      group, however, the proliferation of the HO-8910 cell treated by 100 nM Dex for 6
      days was significantly inhibited with an inhibition rate of 13% (P < 0.01).
      Western blotting showed that Dex down-regulated the p-Akt protein expression. Dex
      time and dose-dependently up-regulated the protein expression of p21(cip1/waf1)
      and p27. The HO-8910 cells co-transfected with p21-luc and pRL-tk-luc and then
      treated with Dex for 24 h showed an higher p21-luc activity, 1.72 times that of
      the control group (P < 0.05). CONCLUSION: The mechanism of inhibiting the
      proliferation by Dex in ovarian cancer cells may involve the depression of PI3K/p
      Akt, and then up-regulation of RhoB and its downstream signal molecules
      p21(cip1/waf1) and p27 proteins.

PMID- 16796924
TI  - [Insulin ultradian pulse model of individuals with overweight and impaired
      glucose tolerance].
AB  - OBJECTIVE: To study the characteristics of insulin ultradian pulses of
      individuals with normal glucose tolerance, overweight, and impaired glucose
      tolerance (IGT). METHODS: Blood samples were taken every 15 minutes from 10
      individuals with normal glucose tolerance, 6 individuals with overweight and 3
      individuals with IGT for 24 hours. Blood glucose, insulin, and C-peptide of every
      time point were measured. Standard diet was used in the study. The 24 h-ISR
      profile was submitted to time series analysis. RESULTS: (1) As given standard
      diet, 2 to 4 pulses occurred after each meal, 3 to 4 pulses occurred during the
      night, and 12 to 15 pulses occurred in the whole 24-hour period. The first
      insulin pulse always occurs 30 to 60 minutes after meal. The maximum amplitude of
      pulse occurred 45 to 90 minutes after meal. These characteristics were not
      significantly different among the 3 groups. (2) The average amplitude of 24-hour
      insulin secretion rate (ISR) of the normal group was 357 pmol/min +/- 11
      pmol/min, significantly lower than those of the overweight and IGT groups (820
      pmol/min +/- 37 pmol/min and 666 pmol/min +/- 53 pmol/min respectively, both P <
      0.05). (3) The average periodicity of insulin ultradian pulse were 75 min and 75 
      90 min in the control group and overweight group respectively. The periodicity
      of insulin ultradian pulse in the IGT group was undefined. (4) The cross
      correlation function were 0.72 +/- 0.11, 0.80 +/- 0.11 and 0.51 +/- 0.11
      respectively in the normal, overweight, and IGT groups. CONCLUSION: (1) As given
      standard diet, the occurring numbers and time of insulin ultradian oscillations
      are not statistically significantly different among the normal, overweight, and
      IGT groups. (2) The insulin secretion amplitude is increased in the overweight
      and IGT groups. (3) The rhythm and concomitance coefficient of the ISR and
      glucose are low in the individuals with IGT.

PMID- 16796925
TI  - [Effects of perioperative enteral immunonutrition on nutritional status, immunity
      and inflammatory response of elderly patients].
AB  - OBJECTIVE: To evaluate the effects of perioperative enteral immunonutrition on
      the nutritional status, immunity, and inflammatory response of the elderly
      patients. METHODS: Eighty malnourished patients aged over 60 with malignant
      gastrointestinal tumors undergoing radical surgery were randomly divided into 2
      groups: experimental group (immunonutrition group, n = 37), and control group (n
      = 43). In the experimental group Supportan and glutamine, with the calorific
      value of 125.4 kJ.kg(-1).d(-1), were given orally or by nasointestinal tube for 5
      days before operation, through jejunostomy or nasointestinal tube during
      operation, and then through nasointestinal tube since the day 2 to day 9 after
      post-operationally. In the control group Nutrition with the same amount of
      calorific value was given in the same manner as mentioned above. Peripheral blood
      samples were collected 5 and 1 days pre-operationally, and 1 and 9 days post
      operatively to examine the serum albumin (ALB), prealbumin (PA), transferrin
      (TFN), CD3, CD4, CD8, CD4/CD8, immunoglobulin (Ig) G, IgA, IgM, and C-reactive
      protein (CRP). RESULTS: Nine days after operation, the serum TFN was 2.18 g/L +/-
      0.29 g/L, PA was 0.23 g/L +/- 0.09 g/L, CD4 was 33.8% +/- 5.4%, CD4/CD8 was 1.17
      +/- 0.12, and IgG was 13.2 g/L +/- 1.8 g/L. all significantly higher than those
      of the control group (1.95 g/L +/- 0.28 g/L, 0.19 g/L +/- 0.03 g/L, 31.1% +/-
      5.2%, 1.05 +/- 0.10, and 12.11 g/L +/- 1.53 g/L respectively, all P < 0.05).
      CONCLUSION: Perioperative enteral immunonutrition improves the nutritional status
      and immune function, und reduces the acute inflammatory response of elderly
      patients.

PMID- 16796926
TI  - [Clinical value of videomediastinoscopy in diagnosis of mediastinal disease].
AB  - OBJECTIVE: To evaluate the role of videomediastinoscopy in the diagnosis of
      disease of the mediastinum. METHODS: We retrospectively reviewed the clinical
      records of the 115 patients who underwent videomediastinoscopy. Local anesthesia
      or general anesthesia was employed. This operation consisted of cervical
      videomediastinoscopy in 102 patients, parasternal videomediastinoscopy in 13
      patients, ninety-one patients had videomediastinoscopy for diagnosis of isolated
      mediastinal mass or lymphadenopathy, 25 patients with non small cell lung cancer
      or suspected lung cancer showed enlarged mediastinal lymph nodes radiographically
      in the chest. RESULTS: Among the patients with mediastinal disease, sarcoidosis
      was diagnosed in 37 patients, tuberculosis in 14 patients, lymphoma in 15
      patients, nodal metastasis in 18 patients, noncaseating granulomata without
      classical "sarcoid" in 6 patients, with the accuracy of 93.3% (84/90); and
      staging of lung cancer in 25 patients, with the accuracy of 100% (25/25). The
      total accuracy of videomediastinoscoy and CT was 94.8% (109/115), 56.5% (65/115),
      respectively. Mean operative time was 26 min. There was neither complication nor
      mortality. CONCLUSION: videomediastinoscopy is a safe and effective procedure for
      the diagnosis of mediastinal disease and the staging of lung cancer.

PMID- 16796927
TI  - [Cytotoxic activities of Celecoxib on leukemic cells and the synergistic effects
      of Celecoxib with Imatinib thereupon].
AB  - OBJECTIVE: To explore the effects of Celecoxib on cell growth, early apoptosis,
      PRb and P27(Kip) protein expression of human leukemic cells of the line K562 and
      to determine its synergistic effects in combination of Imatinib. METHODS: K562
      cel1s were incubated with Celecoxib of the concentrations of 0, 10, 20, 40, 80,
      and 160 micromol/L for 36 hours, the cell vitality was determined by MTT assay,
      the early apoptosis was examined by flow cytometry (FC). The percentage of
      annexin V positive was detected by FC so as to evaluate the early apoptosis. The
      expression of PRb and P27(Kip) protein was detected by Western blotting. Another
      K562 cells were incubated with Celecoxib of the concentration of 40 micromol/L,
      Imatinib of the concentration of 0.2 micromol/L, or Celecoxib 40 micromol/L +
      Imatinib 0.2 micromol/L for 36 hours. Then the cell vitality and early apoptosis
      of the cells were detected so as to evaluate the synergistic effects of the
      combination of Celecoxib and Imatinib. RESULTS: Celecoxib inhibited the K562
      cells vitality significantly in a dose-dependent manner. The apoptotic rate of
      K562 cells was elevated with the increasing Celecoxib concentration. Celecoxib
      down-regulated the expression of PRb protein and up-regulated the expression of
      P27(Kip) protein in the K562 cells. The combination of Celecoxib and Imatinib
      exhibited evidently synergistic effects in terms of anti-proliferation on K562
      cells. CONCLUSION: Celecoxib inhibits the proliferation and induces apoptosis on
      leukemic cells in a dose-dependent fashion. The anti-proliferation effect of
      Celecoxib may be associated with the down-regulation of PRb expression and up
      regulation of P27(Kip) expression. Combination of Celecoxib and Imatinib has
      obviously synergistic effects in terms of anti-proliferation on K562 cells.

PMID- 16796928
TI  - [Influence of pulmonary artery perfusion with solution of washed red blood cells
      on lung injury after cardiopulmonary bypass].
AB  - OBJECTIVE: To observe the influence of intra-operative pulmonary artery perfusion
      with hypothermic washed red blood cell (RBC) solution on lung injury after
      cardiopulmonary bypass (CPB). METHODS: Thirty patients of mitral disease with
      pulmonary hypertension undergoing mitral valve replacement were randomly divided
      into 2 equal groups: control group, and perfusion group (with the pulmonary
      artery infused with 4 degrees C washed RBC protective solution during CPB). The
      blood cell count, pulmonary vascular resistance (PVR), white blood cell (WBC)
      ratio (venous blood/arterial blood), plasma malonyldialdehyde (MDA), and
      oxygenation index (OI), were measured and the time of mechanical ventilation was
      obtained as well. RESULTS: (1) The PVR at the end of CPB, and 12 h and 24 h after
      CPB of the perfusion group were 46.4 kPa.s.L(-1) +/- 8.1 kPa.s.L(-1), 48.5
      kPa.s.L(-1) +/- 7.0 kPa.s.L(-1), and 36.1 kPa.s.L(-1) +/- 6.3 kPa.s.L(-1)
      respectively, all significantly lower than those of the control group (65.7
      kPa.s.L(-1) +/- 5.3 kPa.s.L(-1), 79.8 kPa.s.L(-1) +/- 8.7 kPa.s.L(-1), and 47.9
      kPa.s.L(-1) +/- 7.1 kPa.s.L(-1) respectively, all P < 0.05). (2) The levels of
      MDA at the end of CPB, and 12 h and 24 h after CPB of the perfusion group were
      14.3 mmol/L +/- 0.8 mmol/L, 16.1 mmol/L +/- 0.7 mmol/L, and 13.3 mmol/L +/- 0.5
      mmol/L respectively, all significantly lower than those of the control group
      (18.9 mmol/L +/- 0.9 mmol/L, 21.6 mmol/L +/- 0.4 mmol/L, and 22.5 mmol/L +/- 0.7
      mmol/L respectively, all P < 0.05). (3) The WBC ratios of vein and artery (V/A) a
      the end of CPB and 12 h after CPB of the perfusion group were 1.16 +/- 0.05 and
      1.20 +/- 0.05 respectively, both significantly lower than those of the control
      group (1.53 +/- 0.07 and 1.68 +/- 0.25 respectively (both P < 0.01). (4) The OI
      at the end of CPB, and 12 h and 24 h after CPB of the perfusion group were 370 +/
      33, 388 +/- 41, and 414 +/- 39 respectively, all significantly higher than those
      of the control group (217 +/- 30, 210 +/- 36, and 222 +/- 33 respectively (all P
      < 0.05). (5) The time of mechanical ventilation the perfusion group was 13 h +/-
      4 h, significantly shorter than that of the control group (27 h +/- 6 h, P <
      0.01). CONCLUSION: Pulmonary artery perfusion with hypothermic washed RBC
      protective solution alleviates the lung injury after cardiopulmonary bypass.

PMID- 16796929
TI  - A systematic review and economic model of the effectiveness and cost
      effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment
      of attention deficit hyperactivity disorder in children and adolescents.
AB  - OBJECTIVES: To assess the clinical and cost-effectiveness of oral methylphenidate
      hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in
      children and adolescents (<18 years of age) diagnosed with attention deficit
      hyperactivity disorder (ADHD) (including hyperkinetic disorder). DATA SOURCES:
      Electronic databases covering 1999--July 2004 for MPH, 1997--July 2004 for DEX
      and 1981--July 2004 for ATX. REVIEW METHODS: Selected studies were assessed using
      modified criteria based on CRD Report No. 4. Clinical effectiveness data were
      reported separately for each drug and by the type of comparison. Data for MPH
      were also analysed separately based on whether it was administered as an
      immediate release (IR) or extended release (ER) formulation. For all drugs, the
      data were examined by dose. Data for the core outcomes of hyperactivity (using
      any scale), Clinical Global Impression [as a proxy of quality of life (QoL)] and
      adverse events were reported. For crossover studies, the mean and standard
      deviation (SD) for each outcome were data extracted for end of trial data (i.e.
      baseline data were not considered). For parallel studies, change scores were
      reported where given, otherwise means and SDs were presented for end of trial
      data. In addition, mean differences with 95% confidence intervals were calculated
      for each study. For adverse events, self-ratings were reported when used,
      otherwise, parent reports were utilised. Percentages of participants reporting
      adverse events were used to calculate numbers of events in each treatment arm.
      All the clinical effectiveness data and economic evaluations (including
      accompanying models) included in the company submissions were assessed. A new
      model was developed to assess the cost-effectiveness of the alternative
      treatments in terms of cost per quality-adjusted life-year. To achieve this, a
      mixed treatment comparison model was used to estimate the differential mean
      response rates. Monte Carlo simulation was used to reflect uncertainty in the
      cost-effectiveness results. RESULTS: In total, 65 papers met the inclusion
      criteria. The results suggest that MPH and DEX are effective at reducing
      hyperactivity and improving QoL (as determined by Clinical Global Impression) in
      children, although the reliability of the MPH study results is not known and
      there were only a small number of DEX studies. There was consistent evidence that
      ATX was superior to placebo for hyperactivity and Clinical Global Impression.
      Studies on ATX more often reported the study methodology well, and the results
      were likely to be reliable. Very few studies made direct head-to-head comparisons
      between the drugs or examined a non-drug intervention in combination with MPH,
      DEX or ATX. Adequate and informative data regarding the potential adverse effects
      of the drugs were also lacking. The results of the economic evaluation clearly
      identified an optimal treatment strategy of DEX first-line, followed by IR-MPH
      for treatment failures, followed by ATX for repeat treatment failures. Where DEX
      is unsuitable as a first-line therapy, the optimal strategy is IR-MPH first-line,
      followed by DEX and then ATX. For patients contraindicated to stimulants, ATX is
      preferred to no treatment. For patients in whom a midday dose of medication is
      unworkable, ER-MPH is preferred to ATX, and ER-MPH12 appears more cost-effective
      than ER-MPH8. As identified in the clinical effectiveness review, the reporting
      of studies was poor, therefore this should be borne in mind when interpreting the
      model results. CONCLUSIONS: Drug therapy seems to be superior to no drug therapy,
      no significant differences between the various drugs in terms of efficacy or side
      effects were found, mainly owing to lack of evidence, and the additional benefits
      from behavioural therapy (in combination with drug therapy) are uncertain. Given
      the lack of evidence for any differences in effectiveness between the drugs, the
      economic model tended to be driven by drug costs, which differed considerably.
      Future trials examining MPH, DEX and ATX should include the assessment of
      tolerability and safety as a priority. Longer term follow-up of individuals
      participating in trials could further inform policy makers and health
      professionals. Such data could potentially distinguish between these drugs in a
      clinically useful way. In addition, research examining whether somatic complaints
      are actually related to drug treatment or to the disorder itself would be
      informative.

PMID- 16796930
TI  - The clinical effectiveness and cost-effectiveness of enzyme replacement therapy
      for Gaucher's disease: a systematic review.
AB  - OBJECTIVES: The aim of this review is to determine the clinical effectiveness and
      cost-effectiveness of enzyme replacement therapy (ERT) in the treatment of
      symptomatic Gaucher's disease. DATA SOURCES: Major electronic databases were
      searched from their inception to August 2003; and updated from January 2003 to
      July/August 2004. REVIEW METHODS: Databases were searched for studies that met
      the criteria and selected data were extracted and evaluated. Studies were
      assessed for their relevance to the UK context and the review objective. The
      bibliographic databases were also searched to identify existing cost studies,
      economic evaluations and models. A Markov decision model was constructed based on
      patients moving between states defined by the modified Severity Score Index
      (SSI). Most of the parameters were derived from the published literature. ERT was
      assumed to restore patients to full health in the base case. RESULTS: Sixty-three
      studies were included, all suggestive of benefit with ERT. However, the way in
      which the effects translate into patient well-being and survival or the need for
      services and resources has not been reliably estimated. Quality of life
      improvements with ERT have been reported. Nonetheless, studies based on the Short
      Form 36 (SF-36) indicate that patients treated with ERT continue to have reduced
      health-related quality of life (HRQoL) compared with the general population. No
      study attached utility values to quality of life measures for ERT-treated
      patients. Thirty-one studies relevant to the natural history of the disease were
      found. Sixteen looked at multiple clinical characteristics of a cohort of
      patients with type I Gaucher's disease. There was considerable within-study and
      between-study heterogeneity, but all showed that Gaucher's disease was a
      progressive condition. Some suggested that the disease may become more indolent
      in adulthood; however, studies were discrepant on this point. Most disease is
      diagnosed in adulthood, although about one-quarter presented in childhood, these
      patients having the most severe symptoms and greatest rate of progression.
      Modelling of natural history was undertaken using the five papers that reported
      the SSI for each patient, along with patient-level data on age, age at diagnosis,
      splenectomy status and genotype, to address the question of whether disease
      stabilises in adulthood and the degree of correlation between phenotype and
      genotype. Analysis of the available data suggested that disease progression is
      likely to slow markedly in adulthood and that genotype is a useful predictor of
      clinical expression of the disease. Five studies looked at quality of life. Data
      on this topic were also obtained from the registries. The evidence suggests that
      the vast majority of the clinical characteristics of type I Gaucher's disease
      have little impact on subjective HRQoL and that therefore for the majority of
      people with type I Gaucher's disease this may not be a severe condition. Bone and
      skeletal symptoms contribute most to the morbidity of the disease and can lead to
      severe pain and immobility. The mean cost per patient treated was approximately
      pounds sterling 86,000 per annum in England and Wales. The cost per patient
      varied considerably by dose. Four existing economic evaluations were found, all
      of which calculated a very high cost per quality-adjusted life-year (QALY). Using
      the Markov decision model, ERT was assumed to restore patients to full health in
      the base case. The estimated incremental cost per QALY [incremental cost
      effectiveness ratio (ICER)] in the base case ranged from pounds sterling 380,000
      to pounds sterling 476,000 per QALY, depending on genotype. Univariate
      sensitivity analyses examined ERT not restoring full health, more severe disease
      progression in the untreated cohort, and only treating the most severely affected
      patients. These produced ICERs of approximately pounds sterling 1.4 million,
      pounds sterling 296,000 and pounds sterling 275,000 per QALY, respectively. The
      base-case unit cost of the drug is pounds sterling 2.975. The unit cost would
      have had to be reduced ten-fold, to pounds sterling 0.30, to obtain an ICER of
      pounds sterling 30,000 per QALY. At a unit cost of pounds sterling 1 the ICER
      would be pounds sterling 120,000 per QALY. CONCLUSIONS: Although ERT for treating
      the 'average' Gaucher's disease patient exceeds the normal upper threshold for
      cost-effectiveness seen in NHS policy decisions by over ten-fold, some argue that
      since orphan drug legislation encouraged the manufacture of Cerezyme, and
      Gaucher's disease can be defined as an orphan disease, the NHS has little option
      but to provide it, despite its great expense. More information is required before
      the generalisability of the findings can be determined. Although data from the UK
      have been used wherever possible, these were very thin indeed. Nonetheless, even
      large errors in estimates of the distribution of genotype, genotype--phenotype
      associations, effectiveness and numbers of patients will not reduce the ICER to
      anywhere near the upper level of treatments usually considered cost-effective.
      Further research could help to clarify the many uncertainties that exist.
      However, although doing so will be of clinical interest, it is questionable
      whether, within the current pricing environment, such research would have any
      substantive impact on policy decisions. It is highly improbable that, whatever
      the findings of such research, the ICER could be brought down by the orders of
      magnitude required to make ERT an efficient use of health service resources. (The
      possible exception to this would be investigating the most efficient alternative
      treatment strategies for using ERT in a paediatric population only.) Moreover, if
      under equity considerations for orphan diseases the NHS feels it is important to
      provide this drug, regardless of its cost-effectiveness, then refining the
      precision of the ICER estimate also becomes superfluous.

PMID- 16796931
TI  - [Early complications in patients with pulmonary embolism].
AB  - BACKGROUND AND OBJECTIVE: Mortality, recurrences and hemorrhages are the most
      serious early complications of pulmonary embolism (PE). We intended to ascertain
      the frequency and mechanisms of complications within the first 10 days after PE
      was diagnosed. PATIENTS AND METHOD: We included patients suspected of suffering
      PE between December 2003 and August 2004 from 8 hospitals. We performed a
      multicenter observational prospective study of 8 Spanish hospitals with
      consecutive outpatients diagnosed with PE. Database of clinical variables:
      computerized Registry of Patients with Venous Thromboembolism (RIETE). Statistic
      analysis included chi2 and Student's t test to compare the 2 groups of patients
      (with and without complications). RESULTS: Six hundred eighty one patients were
      included, 336 men and 345 women (mean age 66 and 70, respectively). During the
      first 10 days, 33 (4.8%) of them died, and 22 (3.2%) had an hemorrhage yet no
      recurrences appeared. Previous immobilization and the presence of respiratory
      failure, cancer or renal failure were significantly associated with early
      complications while previous surgery and thoracic pain were not associated with
      those. CONCLUSIONS: Early complications and some of the associated factors were
      in agreement with published data. Other situations such as previous surgery or
      thoracic pain appeared to be protective factors.

PMID- 16796932
TI  - [Prognostic value of headache in cardioembolic stroke].
AB  - BACKGROUND AND OBJECTIVE: To characterize the clinical features, prognosis and
      clinical predictors of headache in cardioembolic stroke (CS). PATIENTS AND
      METHOD: Descriptive study of 480 patients with CS included in the Sagrat Cor
      Hospital of Barcelona Stroke Registry over a 17 year period. The vascular risk
      factors, clinical profiles and topographic data in CS with and without headache
      were compared. The independent predictive value of each variable on the
      development of headache in CS was assessed with a logistic regression analysis.
      RESULTS: Headache was diagnosed in 38 of 480 patients (7.9%) with CS Early
      neurologic deterioration was present in 40 patients (8.3%), and was significantly
      more frequent in patients with than without headache (17.5% vs 7%; p < 0.03). The
      presence of early neurologic deterioration was a significant predictive variable
      associated with headache in CS in the 2 logistic regression models (odds ratio
      [OR] = 3.34, and OR = 3.36). Other clinical variables were: cranial nerve palsy
      (OR = 7.54; 95% confidence interval [CI], 1.98-28.70), ataxia (OR = 4.88; 95% CI,
      1.65-14.50), ischemic heart disease (OR = 3.02; 95% CI, 1.41-6.45),
      hyperlipidemia (OR = 2.61; 95% CI, 1.08-6.28), age (OR = 0.96; 95% CI, 0.93
      0.99), and sudden onset (OR = 0.43; 95% CI, 0.21-0.91). Topographic profile were:
      posteroinferocerebellar artery involvement (OR = 21.41; 95% CI, 3.10-148.04),
      basilar artery involvement (OR = 9.04; 95% CI, 1.87-43.66) and cerebral posterior
      involvement (OR = 6.12; 95% CI, 2.30-16.29). CONCLUSIONS: Headache in CS is more
      frequent in vertebrobasilar involvement. Headache is related with early
      neurological deterioration and associated with increased morbidity and mortality.

PMID- 16796933
TI  - [Estimation of overall cardiovascular risk from coronary risk. A cohort study].
AB  - BACKGROUND AND OBJECTIVE: The coronary risk (CR) is a good approximation of the
      global cardiovascular risk (GCR). Multiplying the CR per 1.3 we obtain the GCR,
      but we don't know if it is certain in our country. PATIENTS AND METHOD:
      Prospective cohort study with 851 patients of ages between 35-74 years old,
      without cardiovascular disease and followed during 5 years. CR include myocardial
      ischemia (angor pectoris or myocardial infarction). GCR include CR,
      cerebrovascular disease, and peripheral vascular disease. RESULTS: We registered
      21 myocardial ischemia cases, 15 cerebrovascular disease cases and 8 peripheral
      vascular disease cases. The accumulated incidence was: 2.5% for CR and 5.2% for
      GCR (difference 2.7%; 95% confidence interval for the difference 0.9-4.6%; p <
      0.05). To estimated GCR we should multiple CR per 2.1. CONCLUSIONS: CR is not a
      good approximation of GCR. We need to developed equation that include not only CR
      but also GCR.

PMID- 16796934
TI  - [Ambulatory treatment of pulmonary thromboembolism].

PMID- 16796935
TI  - [Medical care in disasters].

PMID- 16796936
TI  - [Diffuse large B-cell lymphoma].

PMID- 16796937
TI  - [Venous thromboembolism in patients with cancer].
AB  - The association between neoplastic diseases and venous thromboembolism (VTE) is
      known since long time ago. The nature of this association is bidirectional. On
      one hand, cancer increases the incidence of venous thrombosis and, on the other
      hand, the hemostatic system does play a key role in the tumorigenesis process.
      However, despite recent advances in the field, prophylaxis and treatment of VTE
      in cancer patients is still a challenge, due to the complexity of this type of
      patients. This review is focused on some important points regarding management of
      VTE in cancer patients such as physiopathology, epidemiology, search for hidden
      malignancy, prognostic impact, prophylaxis in the medical and surgical setting,
      or initial and long-term treatment.

PMID- 16796938
TI  - [Roses stamps].

PMID- 16796939
TI  - [Determination of Her2/neu status in breast tumours: PCR versus FISH].

PMID- 16796940
TI  - [Outbreak of Giardia lamblia in a mother-child institution].

PMID- 16796941
TI  - [Gynecomastia by mirtazapin].

PMID- 16796942
TI  - [Septic bursitis due to Serratia marcescens].

PMID- 16796943
TI  - [Primary immunodeficiency asociated with thymoma].

PMID- 16796944
TI  - [Hepatitis B virus reactivation after cessation of prophylaxis with lamivudine in
      a patient with non-Hodgkins lymphoma treated with chemotherapy and rituximab].

PMID- 16796945
TI  - [Transgastric endoscopic surgery: technological delirium or potential advance?].

PMID- 16796946
TI  - [Pancreatic insulinomas].
AB  - Insulinoma is the most frequent neuroendocrine pancreatic tumor. In the present
      study, the clinical and immunohistochemical results of 20 patients who underwent
      surgery between January 1986 and December 2004 were evaluated. Clinical
      presentation, laboratory data, imaging studies, aspects of the surgical
      technique, complication rates and medium- and long-term follow-up were analyzed.
      Surgical treatment was recommended in all patients based on presenting symptoms
      and laboratory signs of hypoglycemia and hyperinsulinemia. In 15 patients, the
      lesion was identified preoperatively. In the 5 remaining patients, intraoperative
      palpation and ultrasonography were used to locate the lesion. The most frequently
      performed surgical procedures were pancreatic resection in 10 patients and
      laparotomic enucleation in the remaining 10. Laparoscopy was used in two
      patients. Two patients developed diabetes mellitus. The most frequent surgical
      complication was pancreatic fistula. No mortality was observed in the present
      series. Symptom reversion, characterized by disappearance of Whipple's triad and
      normal or increased glycemia values compared with preoperative values, was
      observed in all patients.

PMID- 16796947
TI  - [Surgery in complicated colorectal cancer].
AB  - Colorectal cancer continues to have a serious social impact. A large proportion
      of patients are diagnosed at an advanced stage of the disease. Approximately one
      third of patients with colorectal cancer will undergo emergency surgery for a
      complicated tumor, with a high risk of mortality and poorer long-term prognosis.
      The most frequent complications are obstruction and perforation, while massive
      hemorrhage is rare. The curative potential of surgery, whether urgent or
      elective, depends on how radical the resection is, among other factors. In the
      literature on the management of urgent colorectal disease, there are few
      references to the oncological criteria for resection. Uncertainly about the
      optimal treatment has led to wide variability in the treatment of this entity.
      The present article aims to provide a critical appraisal of the controversies
      surrounding the role of surgery and its impact on complicated colorectal cancer.

PMID- 16796948
TI  - [Bull horn wounds in Castellon General Hospital. A study of 387 patients].
AB  - Bull horn lesions are frequent in the Latin world due to spectacles involving
      these animals. These wounds have special characteristics that distinguish them
      from all other lesions. MATERIAL AND METHOD: A retrospective analysis of the
      medical records of patients with bull horn lesions admitted to our service
      between January 1978 and October 2005 was performed. RESULTS: A total of 387
      patients with bull horn lesions were admitted to our service. There were 12
      readmissions due to a new wound in a previously treated patient. Twenty-seven
      patients had two or more lesions. The location of the wounds was: head and neck
      in 12 (3.1%), thorax in 21 (5.4%), upper extremities in 19 (4.9%), abdomen in 44
      (11.3%), perineum in 41 (10.5%), back and lumbar region in 6 (1.5%), and lower
      extremities in 244 (63%). Thirty-one laparotomies were performed and there were
      23 visceral lesions. Surgical treatment in addition to specific procedures
      consisted of irrigation with antiseptic solution, Friedreich, and primary closure
      over drains. Antibiotic and antitetanus vaccinations were administered in all
      patients. The most frequent early complications were: wound devitalization (7
      patients) and infection (6 patients). The most frequent late complication was
      incisional hernia. Three patients died as a result of hypovolemic shock, septic
      shock and gas gangrene. CONCLUSION: Bull horn wounds have special
      characteristics. Familiarity with these lesions is important in areas where
      bullfighting is practiced. Although bull horn wounds are severe, their prognosis
      is good, with few complications and a mortality rate of less than 1%.

PMID- 16796949
TI  - [Hemithyroidectomy in a unilateral goiter: a valid therapeutic option. Review of
      the contralateral hemithyroid ten years after treatment].
AB  - INTRODUCTION: Nodular goiter (NG) is frequent among the general population and is
      considered a diffuse disease. Although NGs are rarely unilateral, they pose a
      dilemma in terms of the extent of the thyroidectomy. The aim of the present study
      was to evaluate the remaining thyroid in patients with NG compared with those
      with follicular adenoma who underwent hemithyroidectomy. PATIENTS AND METHODS:
      Patients who underwent surgery for unilateral NG with over 10 years of
      postoperative follow-up and normal findings on ultrasonography of the
      contralateral thyroid lobe were selected to form the study group (SG). Patients
      with follicular adenoma (with normal contralateral ultrasonography) who underwent
      hemithyroidectomy during the same period were selected to form the control group
      (CG). The selected patients underwent clinical, laboratory and ultrasound
      examinations. Both groups were compared statistically. No significant differences
      were found in age, gender, anesthetic risk, side, postoperative complications,
      length of hospital stay, or postoperative outcome. RESULTS: Less than 10% of the
      patients reported symptoms, and all symptoms were of little significance.
      Ultrasonographic nodules were found in the remaining thyroid lobe in 70% of
      patients in the SG and in 60% of those in the CG, with no statistically
      significant differences. The mean size of the largest nodule was 13.58 +/- 8.01
      in the SG and 9.15 +/- 5.93 in the GC (p = 0.048). No differences were found in
      the anterior-posterior, transverse or longitudinal diameters of the remaining
      lobe. None of the patients underwent reintervention for nodular disease.
      CONCLUSIONS: After hemithyroidectomy, both groups of patients developed nodules
      in the remaining thyroid lobe, with no statistically significant differences.
      Hemithyroidectomy due to unilateral NG involves less risk to the patient and
      therefore we consider it to be a valid option. Long-term ultrasonographic follow
      up seems advisable.

PMID- 16796950
TI  - [Utility of magnetic resonance cholangiography prior to cholecystectomy in acute
      biliary pancreatitis].
AB  - AIM: To analyze the role of magnetic resonance cholangiography (MRC) in
      candidates for cholecystectomy after acute biliary pancreatitis (ABP). METHODS:
      We performed a prospective study of patients with mild ABP (Atlanta criteria)
      admitted to our hospital from January 2004 to March 2005. Diagnosis of ABP was
      based on clinical features, serum amylase levels more than 3 times higher than
      the upper level of normality, and gallstones detected by ultrasonography. In all
      patients, MRC was performed preoperatively. If positive for common bile duct
      stones (CBDS), endoscopic retrograde cholangiopancreatography (ERCP) with
      endoscopic sphincterotomy (ES) was performed, followed by laparoscopic
      cholecystectomy (LC). When MRC was negative, LC was performed directly.
      Intraoperative cholangiography was not routinely performed . RESULTS: Of the 31
      patients admitted, 27 were included (mean age 66.4 +/- 18 years, 78% female).
      Four patients were excluded: 2 refused to undergo cholecystectomy and two had
      severe ABP. The mean interval between onset of ABP and cholecystectomy was 1.7
      months +/- 1.2. Three patients (11.1%) experienced recurrence within 4 weeks of
      the index admission. MRC revealed CBDS in four patients (14.8%). In 3 patients,
      all the gallstones were removed by ERCP and ES. In one patient, 12 gallstones
      were retrieved but attempts to remove a stone from the cystic duct were
      unsuccessful. One patient with preoperative CBDS was readmitted 4 weeks after
      cholecystectomy due to recurrence. Another patient with negative findings on
      preoperative MRC was also readmitted with postcholecystectomy ABP. Twenty-five of
      the 27 patients (93%) have remained asymptomatic after cholecystectomy (median
      follow-up: 16 months [8-22 months]). CONCLUSIONS: MRC should not be routinely
      used in the preoperative evaluation of patients with ABP but is an accurate tool
      in selected patients with this disease.

PMID- 16796951
TI  - [Gastric cancer: probability assessment after lymph node-negative staging and its
      consequences].
AB  - OBJECTIVE: To provide an approach to calculating the probability of error after
      lymph node-negative staging in gastric cancer. PATIENTS AND METHOD: Retrospective
      data of 75 gastric resections for cancer were used to calculate the probability
      of error in general, according to T staging of the TNM classification (6th
      edition) and according to the type of lymphadenectomy performed. A modification
      of a procedure based on Bayes' theorem was used. RESULTS: For all tumors, at
      least 11 negative lymph nodes were required to ensure a true pN0. Two lymph nodes
      were required for T1 tumors, 11 for T2 tumors, and 14 for T3 tumors. A greater
      number of lymph nodes were required for a D2 lymphadenectomy than for a D1
      lymphadenectomy. However, in D2 lymphadenectomy, pN0 stages were almost always
      reliable, while in D1 lymphadenectomy 24% of stagings were unreliable.
      CONCLUSIONS: The present study describes a simple and reproducible mathematical
      model that could help surgeons to determine the accuracy of lymph node-negative
      stages in a substantial group of patients with gastric cancer.

PMID- 16796952
TI  - [Surveillance of shrinkage of polypropylene mesh used in the repair of ventral
      hernias].
AB  - INTRODUCTION: Polypropylene (PP) mesh is one of the most frequently used
      materials in the surgical repair of ventral hernias. Despite the widely
      recognized ability of PP to integrate into the host tissue, these meshes may
      shrink during the healing process in the patient. OBJECTIVE: To quantify
      polypropylene mesh shrinkage. PATIENTS AND METHOD: A radiological follow-up study
      was performed in 23 consecutive patients who underwent surgery for midline
      ventral hernias with diameters of at least 5 cm. PP meshes were marked with
      titanium clips at the ends of their longest transverse and longitudinal axes. X
      rays were performed on the first postoperative day and at 1, 3, 6 and 12 months.
      The distances between clips were measured and the area of the mesh was
      calculated. RESULTS: Seventeen women and six men underwent surgery. In nine
      patients the mesh was placed on the prefascial space (onlay) and in 14 in the
      subfascial space (sublay). There were four seromas in patients with mesh placed
      with the onlay technique. The reduction in the calculated area was 12% at 1
      month, 24% at 3 months, 29% at 6 months and 34% at 12 months. CONCLUSIONS: PP
      mesh provided excellent clinical results. Radiological surveillance revealed
      substantial shrinkage, mainly in the first 3 months after implantation.

PMID- 16796953
TI  - [Oat cell carcinoma of the common bile duct].
AB  - Oat cell tumors in the common bile duct are extremely rare. We describe the case
      of a 76-year-old man with skin and mucous jaundice of 15 days' duration without
      constitutional syndrome. A tumor was diagnosed in the mid portion of the common
      bile duct. After surgical resection, pathological analysis revealed small-cell
      (oat cell) carcinoma. The treatment of these tumors is multidisciplinary. Surgery
      is followed by chemo- and radiotherapy.

PMID- 16796954
TI  - [Iatrogenic tracheal rupture after endotracheal intubation].
AB  - Tracheobronchial rupture after tracheal intubation is rare in clinical practice.
      Possible contributory factors are multiple vigorous attempts at intubation,
      overinflation of the cuff, anatomic alterations, and predisposing individual
      factors. These lesions can be detected by bronchoscopy, which is the most
      effective method to confirm the diagnosis and determine the exact location and
      extent of the tear. We report the case of a woman with membranous tracheal
      rupture after endotracheal intubation. Subcutaneous emphysema, pneumomediastinum
      and bilateral pneumothorax were noted after extubation. The diagnosis was
      confirmed by fiberoptic bronchoscopy and computed tomography scan, and the
      patient required emergency surgical repair.

PMID- 16796955
TI  - [Pulmonary and brain metastases from well-differentiated thyroid carcinoma].
AB  - Total thyroidectomy is the surgical treatment of choice for differentiated
      thyroid carcinoma. Despite this surgical treatment, locoregional and distant
      metastases can develop. Postoperative follow-up should include determination of
      serum thyroglobulin levels and radioactive iodine (131I) and thallium (201Tl)
      whole body scans. These techniques are more reliable in patients who have
      undergone total thyroidectomy. We stress the importance of routine medical follow
      up after surgical treatment of thyroid cancer, even in the absence of symptoms.

PMID- 16796956
TI  - [Image of the month. Intestinal anisakiasis].

PMID- 16796957
TI  - [Severe lower gastrointestinal hemorrhage due to jejunal diverticulosis.
      Preoperative diagnosis by enteroscopy].

PMID- 16796958
TI  - [Obstructive jaundice and cholangitis secondary to hepatic hydatid cyst].

PMID- 16796959
TI  - [Perianal hemangiopericytoma].

PMID- 16796960
TI  - [Epidermoid carcinoma arising in a pilonidal sinus].

PMID- 16796961
TI  - [Cutaneous semiology: a historical perspective of the evolution of basic
      terminology in Spain].
AB  - There are still numerous incompatibilities in the definitions of basic
      dermatological terms. In Spain, the problem is aggravated by the coexistence and
      conflict between two different semantic models, imported from other countries
      (France and the USA). These two models really have different "units": one model
      can be called "essentialist" and the other "nominalist". These models are not
      original to Spain; rather, each one shows the predominance or influence of an
      outside culture. Through a historical and evolutional study, we were able to
      verify that the origin of these semantic models goes back to Joseph Plenck and
      Robert Willan (essentialist model) and to Ferdinand Hebra (nominalist model),
      respectively. An analysis of these models from a historical perspective may help
      in understanding the origin of the current conflicts in the everyday use of
      Spanish dermatological semiology, and may therefore help resolve them.

PMID- 16796962
TI  - [Brief history of Actas Dermo-Sifiliograficas].
AB  - Actas Dermo-Sifiliograficas was founded by Juan de Azua in May 1909. The birth of
      the journal coincided with the founding of the Spanish Academy of Dermatology and
      Venereology, then known as the Spanish Society of Dermatology and Syphiligraphy,
      and it is this organization's official publication. Actas Dermo-Sifiliograficas
      gradually became established, until the year 1936, when its publication was
      interrupted for 14 months at the start of the Spanish Civil War. It resumed
      activity in October 1937 under Sainz de Aja, Gay Prieto and Eduardo de Gregorio.
      In the 1980's, it underwent a crisis that resulted in its exclusion from MEDLINE.
      Actas Dermo-Sifiliograficas gradually recovered under the management of Drs.
      Iglesias, Sanchez-Yus, Fernandez-Herrera and Torrelo, and it has finally been
      included once again in the most consulted medical database in the world.

PMID- 16796963
TI  - [Extravasation of cytostatic agents: a serious complication of oncological
      treatment].
AB  - The extravasation of cytostatic agents is a known, serious situation that can
      easily occur and cause chronic, irreversible damage. The incidence of
      extravasation ranges from 0.1 %-6.5 %, according to different studies. Many cases
      of extravasation can be prevented by systematizing the administration techniques
      for cytostatic agents. We present the clinical and histological characteristics
      of a series of patients with extravasation lesions. Included in the study were
      all patients treated with chemotherapy who developed localized lesions in the
      area of the cytostatic injection after extravasation was detected during
      administration. The patients were studied and followed up for a three-year
      period, from January 2000 to December 2003, inclusive. We found nine cases of
      extravasation among the 2,186 patients who were treated with chemotherapy, which
      represents an incidence of 0.41 %, and 3.4 % of all chemotherapy-induced skin
      lesions. The cytostatic agent most often involved was vinorelbine, and the most
      frequent location was the antecubital fossa. The intensity of the lesions made it
      necessary to delay the next cycle of treatment in 55 % of the cases. The
      histological findings varied depending on when the biopsy was done, showing
      panniculitis with low cellularity together with epidermal lesions attributable to
      direct cytotoxicity. The best treatment for extravasation is prevention, but when
      it has already occurred, measures vary depending on the cytostatic drug
      extravasated and the intensity of the lesions. Conservative measures are
      advisable before surgery.

PMID- 16796964
TI  - [Stevens-Johnson syndrome and toxic epidermal necrolysis].
AB  - INTRODUCTION: The aim of this work is to reflect the clinical experience of the
      Dermatology Department of Hospital General in Valencia with Stevens-Johnson
      syndrome (SJS) and toxic epidermal necrolysis (TEN) or Lyell's syndrome over the
      last 15 years. METHODS: Data on epidemiology, likely causal agents, complementary
      tests, concomitant pathologies, management, evolution and complications was
      gathered through a retrospective study. RESULTS: Thirteen patients were included,
      with a mean age of 53 years. The most frequently involved drugs were antibiotics
      (50 %), followed by anti-convulsants (16.6 %). The mucous membranes were involved
      in 84.6 % of the cases. 61.5 % of the patients presented with systemic symptoms.
      The most frequent laboratory finding was hypoproteinemia. Corticosteroids were
      used in 69 % of the cases, and intravenous immunoglobulins in 15 %. Two
      oncological patients with a diagnosis of TEN died (15 % overall mortality).
      CONCLUSIONS: SJS and TEN are infrequent mucocutaneous reactions, often drug
      induced, with significant associated morbidity and mortality. Their pathogenesis
      is still partially unknown, and no specific treatment has been proven to be
      clearly beneficial; therefore, the best treatment consists of early diagnosis,
      the withdrawal of the suspect drug and support therapy.

PMID- 16796965
TI  - [Replacing systemic with topical corticotherapy in patients with generalized
      bullous pemphigoid and serious steroid-induced iatrogenesis].
AB  - We describe four patients with generalized bullous pemphigoid, who received
      treatment with oral prednisone and suffered serious corticosteroid-induced
      iatrogenesis. In all cases, we decided to quickly withdraw the systemic
      corticosteroid treatment and begin treatment with 0.05 % clobetasol propionate
      (20 g/day). New outbreaks of pemphigoid or significant side effects were not seen
      after this change in medication. The topical treatment went on for five to twelve
      months, and the patients were followed up for extended periods after treatment
      ended, with no recurrences being observed. Systemic corticosteroid treatment may
      be replaced by topical treatment without complications, and this may be
      especially indicated in patients with serious corticosteroid-induced
      iatrogenesis.

PMID- 16796966
TI  - [Contact allergy to 3-dimethylaminopropylamine and cocamidopropyl betaine].
AB  - It has been discovered that all individuals who are allergic to cocamidopropyl
      betaine (CAPB) are sensitized to 3-dimethylaminopropylamine (DMAPA) and to
      amidoamine, molecules which are intermediaries in CAPB synthesis, and which
      persist as impurities in the material that is sold; the amounts vary, depending
      on the quality of the CAPB in the end product. We present three cases of allergic
      contact dermatitis to DMAPA. In all three cases, the skin tests for DMAPA were
      positive, while there was no reaction to CAPB. The current relevance of these
      tests was confirmed by the patients' re-exposure to the suspect products
      themselves, which contained CAPB. Contact allergy to CAPB is now infrequent,
      partly because of the increasing use of new non-irritating surfactants that have
      been introduced on the market in the last decade. However, cases of patients
      allergic to commercial CAPB who only react to DMAPA -and not to CAPB- when they
      are patch tested are still being reported. DMAPA itself, and other molecules like
      amidoamine, would be the true allergens, and some cases of CAPB allergy are
      therefore being overlooked because DMAPA is not always included in the cosmetics
      series. CAPB may no longer be necessary in patch tests, as DMAPA seems to be the
      principal allergenic fraction in this surfactant, and also because manufacturers
      of skin allergens currently prepare CAPB extracts that are so pure that they are
      no longer a good screening tool for contact allergy to commercial CAPB.

PMID- 16796967
TI  - [Acrokeratosis paraneoplastica with bullous lesions associated with esophageal
      squamous cell carcinoma].
AB  - Acrokeratosis paraneoplastica (Bazex syndrome) is characterized by an acral
      eruption with a psoriasiform appearance, which usually presents simultaneously
      with an underlying neoplasm. We describe the case of a 64-year-old male who
      presented with a two-month history of pruritic, flaky, erythematous lesions on
      the palms, backs of the fingers and toes and pinnae, accompanied by bullous
      lesions. The patient also reported progressive dysphagia in the last six months,
      and general wasting with a loss of 15 kg. The digestive endoscopy revealed a
      squamous cell carcinoma in the proximal esophagus. The histopathological study of
      the bullous lesions showed the presence of a subepidermal bulla, and direct
      immunofluorescence revealed granular deposits of IgG, IgA and C3 in the basal
      membrane of the healthy perilesional skin. These clinical/pathological findings
      support the existence of an immunological pathogenic mechanism related to this
      entity.

PMID- 16796968
TI  - [Becker's nevus associated with epidermal nevus: another example of twin
      spotting?].
AB  - Linear epidermal nevi are believed to be caused by an autosomal dominant lethal
      mutation that can only be expressed by mosaicism. Becker's nevus can be explained
      by paradominant inheritance which is only manifested clinically by an acquired
      loss of heterozygosity. We present the case of a 16-year-old female with an
      epidermal nevus located on the left side of the neck, and also a Becker's nevus
      located on the ipsilateral shoulder. It is interesting to speculate that this
      supposed double mosaicism could be another example of "twin spotting" or non
      allelic didymosis, although the possibility that this is a chance association
      cannot be ruled out, as the lesions are not closely associated.

PMID- 16796969
TI  - [Chronic cutaneous fistula secondary to mandibular osteomyelitis].
AB  - Cutaneous fistulas and sinuses in the maxillofacial region secondary to
      osteomyelitis rarely appear in clinical practice. The most frequent cause of
      mandibular osteomyelitis is a dental infection, but it may also be hematogenic in
      origin. The diagnostic criteria for bacterial osteomyelitis are suppuration and
      osteolytic changes in the radiological study. The differential diagnosis of an
      ulcerative lesion in the mandibular area includes several pathologies, such as a
      fistula of dental origin, a reaction to a foreign body, a deep mycotic infection,
      a pyogenic granuloma or a congenital malformation.

PMID- 16796970
TI  - [Cutaneous metastases of rectal adenocarcinoma in a herpetiform distribution].
AB  - We present the case of a 62-year-old male with cutaneous metastases of a rectal
      adenocarcinoma located on the groin and left thigh. Due to their clinical
      similarity, the lesions were initially diagnosed and treated as herpes zoster.
      Cutaneous metastases have variable clinical presentation patterns. They may mimic
      benign skin lesions like epidermoid cysts, lipomas, erysipelas or, as in our
      case, herpes zoster.

PMID- 16796971
TI  - [Gefitinib-induced perforating dermatosis].
AB  - Gefitinib (Iressa) is a new antineoplastic agent that acts by selectively
      inhibiting epidermal growth factor receptor tyrosine kinase (EGFR-TK). It has
      shown activity against several solid tumors. Because of their action mechanism,
      gefitinib and other tyrosine kinase inhibitors have been associated with multiple
      cutaneous effects, most of which are mild and well tolerated. We present a case
      of perforating dermatosis after treatment with gefitinib.

PMID- 16796972
TI  - [Skin lesions from the application of suction cups for therapeutic purposes].
AB  - The application of suction cups or cupping is a medicinal practice that is very
      widespread in Asian countries. The presence of circular areas of erythema,
      ecchymosis or blood blisters symmetrically distributed on the shoulders, back,
      thorax or lumbar area should suggest the use of this technique. The number of
      followers of traditional Chinese medicine is increasing in the Western world, so
      we should be familiar with these practices in order to prevent social and/or
      legal conflicts that may arise from mistaken diagnoses of abuse. We present the
      case of a 65-year-old male with multiple circular, erythematous, bullous lesions,
      symmetrically distributed, which occurred after the application of suction cups
      in the context of polymyalgia rheumatica.

PMID- 16796973
TI  - [Reddish-orange facial papules].

PMID- 16796974
TI  - [Subcutaneous nodules in a newborn].

PMID- 16796975
TI  - [Pemphigus vulgaris treated with rituximab].

PMID- 16796976
TI  - [Subcutaneous sarcoidosis, nodular lesions forming cords or bands].

PMID- 16796977
TI  - [Unilateral Blaschkoid linear lichen planus].

PMID- 16796978
TI  - Expression and activation of mitogen-activated protein kinase in the human
      endometrium during the menstrual cycle.
AB  - OBJECTIVE: The purpose of this study was to investigate the fluctuation of
      expression and activation of mitogen-activated protein kinase in normal human
      endometrium throughout the menstrual cycle. STUDY DESIGN: Thirty-three normal
      endometrial tissues were obtained from fertile women who had undergone
      hysterectomies for reasons other than endometrial disease. Extracellular signal
      regulated kinase, -1, and -2 expression were studied by immunohistochemistry.
      Moreover, extracellular signal-regulated kinase activity was analyzed by gel
      kinase assay. RESULTS: Western blotting analysis with anti-pan-extracellular
      signal-regulated kinase antibody mainly demonstrated an immunoreactive band of 42
      kd that corresponded to extracellular signal-regulated kinase 2 in the
      endometrium. The expression of extracellular signal-regulated kinase 2 tended to
      increase in the secretory phase. Immunohistochemical analysis for extracellular
      signal-regulated kinase 1 in endometrial sections revealed a weak staining of
      glands and almost no staining of stromal cells. Immunohistochemical analysis for
      extracellular signal-regulated kinase 2 in endometrial sections revealed a
      distinct staining of glands in both proliferative and secretory phases and a weak
      staining of stromal cells. Although the intensity of staining for extracellular
      signal-regulated kinase 2 in stromal cells did not change during the secretory
      phase, in the glands the extracellular signal-regulated kinase 2 was highly
      stained in the mid-to-late secretory phase. In gel kinase assay revealed that
      extracellular signal-regulated kinase activity was increased significantly in the
      mid-to-late secretory phase. CONCLUSION: Expression and activation of
      extracellular signal-regulated kinase in the human endometrium was increased
      particularly during the secretory phase. We suggest that fluctuation of
      extracellular signal-regulated kinase in the human endometrium may be induced by
      ovarian steroid hormones.

PMID- 16796980
TI  - Sonographic estimate of birth weight among high-risk patients: feasibility and
      factors influencing accuracy.
AB  - OBJECTIVE: This study was undertaken to determine the feasibility of detecting
      abnormal fetal growth among patients undergoing biophysical profile (BPP) and to
      identify the factors those influence the accuracy. STUDY DESIGN: Retrospectively
      singletons with reliable gestational age (GA) having a BPP were identified. Fetal
      growth restriction (FGR) and large-for-gestational age (LGA) were based on
      estimated or actual birth weight 10% or less or 90% or greater for GA,
      respectively. Likelihood ratio (LR), odds ratio (OR) and 95% CIs were calculated
      and multivariate predictive models used. RESULTS: Among the 1934 consecutive
      patients that met the inclusion criteria, the LR of detecting FGR was 10.9 and of
      LGA, 17.4. Multivariate analysis indicates that accurate classification of fetal
      growth is significantly better with hydramnios (OR 1.78, 95% CI 2.68), if the GA
      is less than 32 weeks (OR 3.71, 95% CI 1.50-9.16) or GA is between 32.1 and 36.9
      weeks (OR 1.43, 95% CI 1.05-1.96). CONCLUSION: It is feasible to accurately
      identify abnormal growth among high-risk patients and to delineate factors that
      influence the correct classification of fetal growth.

PMID- 16796981
TI  - The Alabama Preterm Birth Study: intrauterine infection and placental histologic
      findings in preterm births of males and females less than 32 weeks.
AB  - OBJECTIVE: The objective of the study was to determine whether there are
      differences in the placental histology and various markers of
      infection/inflammation between preterm male and female fetuses. STUDY DESIGN: The
      placentas and umbilical cords of 446 infants born at 23 to 32 weeks were examined
      histologically, cultured for aerobic and anaerobic bacteria and mycoplasmas, and
      the interleukin-6 levels in cord blood determined. RESULTS: Male infants were
      significantly more likely to have positive placental cultures than female infants
      (63.4% versus 51.8%, P = .01, odds ratio 1.5, 1.0 to 2.4). Cord blood Mycoplasma
      hominis and Ureaplasma urealyticum infections were marginally more common in male
      than female fetuses (27.6% versus 19.2%, P = .06, odds ratio 1.7, 0.9 to 2.9),
      but cord blood interleukin-6 levels were not different between male and female
      fetuses. The only significant histologic difference between male and female
      placentas was in decidual lymphoplasmacytic cell infiltration (6.3% versus 0.9%,
      P = .003, odds ratio 8.3, 1.8 to 39.0). Males had a higher percentage of decidual
      lymphohistiocytic cell infiltration, but the differences were not significant
      (11.3% versus 7.4%, P = .160, odds ratio 1.6, 0.8 to 3.2). CONCLUSION: Male
      infants were significantly more likely to have positive placental membrane
      cultures than female infants. Decidual lymphoplasmacytic cell infiltrations were
      more common in male versus female placentas, confirming a previous observation
      and suggesting that a maternal immune reaction to fetal tissue may be more common
      in male fetuses.

PMID- 16796982
TI  - Hypervolemia of pregnancy is not maintained in mice chronically overexpressing
      angiotensinogen.
AB  - OBJECTIVE: Women who develop pre-eclampsia show significantly less hypervolemia
      of pregnancy, compared with controls. We have shown that chronically elevated
      angiotensinogen expression increases a woman's risk of developing pre-eclampsia.
      Our objective was to determine whether increased angiotensinogen expression is
      sufficient to cause failed hypervolemia. STUDY DESIGN: To isolate the effects of
      elevated angiotensinogen expression, we studied transgenic mice with either 2 or
      3 copies of the murine angiotensinogen gene. Plasma volume was measured by Evans
      blue dye dilution, and kidney sections were immunostained for angiotensinogen and
      renin. RESULTS: Three-copy mice failed to maintain hypervolemia after
      midgestation (P < .01) and failed to up-regulate renin expression in the distal
      nephron, compared with 2-copy controls. Intrarenal angiotensinogen was up
      regulated during pregnancy in both genotypes. CONCLUSION: Chronically elevated
      angiotensinogen expression is sufficient to cause failed hypervolemia of
      pregnancy. Whether this observation is related to failed up-regulation of distal
      tubule renin expression requires further study.

PMID- 16796983
TI  - Intra- and interobserver agreement and statistical clustering of placental
      histopathologic features relevant to preterm birth.
AB  - OBJECTIVE: Many previous studies of agreement in identifying placental
      histopathologic lesions have been based on small sample sizes, and none has
      examined whether individual histologic features cluster robustly together within
      and between observers. STUDY DESIGN: We studied 767 placental specimens from case
      control studies of preterm birth and preeclampsia nested within a prospective
      cohort of pregnant women recruited from 4 large Montreal maternity hospitals. The
      specimens were fixed, embedded, stained, and examined using a standardized
      protocol; a 10% random sample (n = 81) was then blindly reexamined at least 6
      months later by the same pathologist and a second pathologist. RESULTS: Intra-
      and interobserver agreement were high (kappa > or = 0.50) for membrane
      inflammation, funisitis, and umbilical cord vasculitis, and these 3 features were
      robustly clustered statistically, consistent with an underlying mechanism of
      ascending infection. Agreement and clustering were also high or moderate for
      features of placental underperfusion: infarction, decidual vasculopathy, and
      syncytial knotting. CONCLUSION: Our results should help researchers to interpret
      future findings relating placental histopathology to preterm birth, preeclampsia,
      and other adverse pregnancy outcomes, and to their etiologic determinants and
      causal pathways.

PMID- 16796984
TI  - Pregnancy after uterine artery embolization for leiomyomata: a series of 56
      completed pregnancies.
AB  - OBJECTIVE: This study was undertaken to evaluate the incidence and outcome of
      pregnancies after uterine artery embolization (UAE) for symptomatic uterine
      fibroids. STUDY DESIGN: A retrospective analysis of all pregnancies after UAE by
      a single interventional radiologist. RESULTS: Fifty-six completed pregnancies
      were identified in approximately 1200 women after UAE. One hundred eight patients
      were attempting to become pregnant and 33 of these became pregnant. Thirty-three
      (58.9%) of the 56 pregnancies had successful outcomes. Six (18.2%) of these were
      premature. Seventeen (30.4%) pregnancies miscarried. There were 3 terminations, 2
      stillbirths, and 1 ectopic pregnancy. Of the 33 deliveries, 24 (72.7%) were
      delivered by cesarean section. There were 13 elective sections and the indication
      for 9 was fibroids. There were 6 cases of postpartum hemorrhage (18.2%).
      CONCLUSION: Compared with the general obstetric population, there is a
      significant increase in delivery by cesarean section and an increase in preterm
      delivery, postpartum hemorrhage, miscarriage, and lower pregnancy rates. When
      taking into account the demographics of the study population, these results can
      be partly explained. There were no other obstetric risk identified.

PMID- 16796985
TI  - Post-call cognitive function and satisfaction in medical students on different
      call schedules: a prospective observational pilot study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of 2 different
      call schedules on post-call cognitive function and satisfaction. STUDY DESIGN:
      This is a prospective observational pilot study of 20 third-year medical
      students. A computerized cognitive function test was administered to students
      with call every fourth night or a week of 12-hour "night float" shifts.
      Questionnaires were completed to assess satisfaction on different call schedules.
      RESULTS: There was no significant difference in cognitive functioning scores for
      students on either call schedule. Responses on questionnaires indicate that night
      float allows students to feel more alert for clinical duties (P = .03).
      CONCLUSION: There is no significant impact of sleep deprivation on cognitive
      scores; however, night float allows students to feel subjectively more alert for
      clinical duties.

PMID- 16796986
TI  - Oral contraceptives and premenstrual symptoms: comparison of a 21/7 and extended
      regimen.
AB  - OBJECTIVE: The purpose of this study was to assess the incidence and severity of
      premenstrual-type symptoms in patients converted from a 21/7 oral contraceptive
      (OC) regimen to an extended regimen. STUDY DESIGN: This was a single center
      prospective analysis of the single item Scott and White (S&W) Mood Scale and the
      Penn State Daily Symptom Report (DSR17) during a 21/7-day followed by a 168-day
      extended regimen of an OC containing 3 mg of drosperinone and 30 microg of
      ethinyl estradiol (DRSP/EE). RESULTS: Of the 114 patients who began the study,
      111 completed the preextension 21/7 phase of the study. There were significant
      differences in severity in the DSR17 and the S&W mood scale among days of the
      cycle. (P < .0001) The highest values in both scales occurred during the 7-day
      hormone free interval (HFI) of the 21/7 cycles (P < .001). Of the 111 patients
      who completed the 21/7 phase of the study, 102 (92%) completed the 168-day
      extended regimen. During the extended phase of the study, subjects were divided
      into 2 groups: those with a 100% increase in symptoms from the first half to the
      second half of the last 21/7 cycle were labeled as high cyclic variability,
      whereas those with lesser or no cyclic change were labeled as low cyclic
      variability. There were 55 (54%) with increased cyclic variability in mood scores
      peaking during the 7-day HFI. Premenstrual-type symptoms measured by both the S&W
      mood scale and the DSR17 instrument decreased during the extended DRSP/EE OC
      regimen (P < .0001) compared with the preceding 21/7 cycle, with the greatest
      improvement detected in the sixth month of continuous OCs (P < .003). The patient
      group with greatest cyclic variability during the 21/7 regimen demonstrated the
      most improvement during the 168-day regimen (P < .0001). The single item S&W mood
      scale was significantly (P < .05) correlated to each of 17 elements of the DSR17
      with Spearman R correlation coefficients of 0.25 to 0.57. The greatest
      correlation coefficient (Spearman's R = 0.66) is with the sum of all 17 items.
      CONCLUSION: A 168-day extended regimen of DRSP/EE led to a decrease in
      premenstrual-type symptoms compared with the 21/7-day regimen.

PMID- 16796988
TI  - Subcutaneous management of vertical incisions with 3 or more centimeters of
      subcutaneous fat.
AB  - OBJECTIVE: This study was undertaken to determine the most appropriate management
      of the subcutaneous tissue of midline vertical incisions with 3 cm or more of
      subcutaneous fat. STUDY DESIGN: Patients undergoing surgery within the Division
      of Gynecologic Oncology at University of South Florida and East Tennessee State
      University with 3 cm or more of subcutaneous fat were randomly assigned to 1 of 3
      groups: suture approximation of Camper's fascia, closed suction drainage of the
      subcutaneous space, or no intervention as a control group. Participants were
      evaluated daily during postoperative hospitalization and at 2 and 6 weeks
      postoperatively as an outpatient. Demographic information, perioperative data,
      and wound complications were recorded and then analyzed with chi2, t test,
      analysis of variance, and logistic regression where appropriate. RESULTS: Two
      hundred twenty-five patients were enrolled with 222 eligible for evaluation.
      Wound complications were observed in 34 (15.3%) patients, and 25 of these women
      also had wound disruption. Overall wound complication and wound disruption rates
      were not significantly different between groups: suture (12.8%, 7.7%), drain
      (17.9%, 14.9%), control (15.6%, 11.7%); P = .70 and P = .39, respectively.
      CONCLUSION: Suture approximation or drainage of the subcutaneous tissues of women
      with 3 cm or more subcutaneous fat measured in midline vertical incisions
      resulted in no significant change in the incidence of overall wound complications
      or superficial wound disruption.

PMID- 16796990
TI  - Amniotic fluid intercellular adhesion molecule-1 is a marker for Ureaplasma
      infection in women with preterm labor.
AB  - OBJECTIVE: The objective of the study was to determine the amniotic fluid soluble
      intercellular adhesion molecule-1 concentrations in women with preterm labor in
      relation to intra-amniotic infection. STUDY DESIGN: Amniotic fluids from 125
      women with preterm labor (78 with preterm delivery and 47 with term deliveries)
      were examined for both soluble intercellular adhesion molecule-1 concentrations
      and intra-amniotic infection with Ureaplasma species. A chi2 test, or Fisher's
      exact test, when appropriate, was used for statistical analysis. RESULTS: In the
      preterm delivery group, 45% (35 of 78) had intra-amniotic infection with
      Ureaplasma species, compared with 19% (9 of 47) in the term delivery group (P =
      .004). In women with intra-amniotic infection, 26% (9 of 38) had soluble
      intercellular adhesion molecule-1 levels above 1290 ng/ml. Only 2.3% (1 of 43) in
      the preterm delivery group without intra-amniotic infection attained this
      diagnostic level (P = .004). In contrast, there was no significant difference in
      soluble intercellular adhesion molecule-1 levels between those with or without
      intra-amniotic infection in the term delivery group. CONCLUSION: Amniotic fluid
      soluble intercellular adhesion molecule-1 concentrations exceeding 1290 ng/ml can
      be used as a marker for intra-amniotic infection with Ureaplasma in patients with
      preterm labor.

PMID- 16796991
TI  - Prediction of severe fetal anemia in red blood cell alloimmunization after
      previous intrauterine transfusions.
AB  - OBJECTIVE: This study was undertaken to determine the detection of fetal anemia
      and false-positive rates by fetal middle cerebral artery peak systolic velocity
      (MCA-PSV) and the estimated daily decrease of hemoglobin (Hb) in red blood cell
      alloimmunized pregnancies that had previous fetal transfusions. STUDY DESIGN: We
      examined the relation between MCA-PSV measured before cordocentesis, and fetal Hb
      at the time of the second (n = 42) and third (n = 31) intrauterine blood
      transfusions. In addition, the daily Hb drop between the transfusions was
      calculated. RESULTS: The MCA-PSV provided significant prediction of severe anemia
      (Hb deficit > or = 6 g/dL) for the second but not for the third transfusion.
      Detection of 95% of severely anemic fetuses was achieved with a false-positive
      rate of 37% for the second transfusion and 90% for the third, compared with 14%
      in our previous study for the first transfusion. In patients who had received 2
      previous transfusions, the only significant predictor of fetal anemia was the
      estimation of the Hb from the measured posttransfusion Hb after the second
      transfusion and the assumption that the rate of decrease in fetal Hb is 0.3 g/dL
      per day. CONCLUSION: Prediction of severe fetal anemia after one transfusion is
      less accurate than in nontransfused fetuses. The MCA-PSV is not useful in
      predicting severe anemia in fetuses that already had 2 previous transfusions.

PMID- 16796993
TI  - Chaperone-like activities of alpha-synuclein: alpha-synuclein assists enzyme
      activities of esterases.
AB  - Alpha-synuclein, a major constituent of Lewy bodies (LBs), has been implicated to
      play a critical role in the pathogenesis of Parkinson's disease (PD), although
      the physiological function of alpha-synuclein has not yet been known. Here we
      have shown that alpha-synuclein, which has no well-defined secondary or tertiary
      structure, can protect the enzyme activity of microbial esterases against stress
      conditions such as heat, pH, and organic solvents. In particular, the flexibility
      of alpha-synuclein and its C-terminal region seems to be important for complex
      formation, but the structural integrity of the C-terminal region may not be
      required for stabilization of enzyme activity. In addition, atomic force
      microscopy (AFM) and in vivo enzyme assays showed highly specific interactions of
      esterases with alpha-synuclein. Our results indicate that alpha-synuclein not
      only protects the enzyme activity of microbial esterases in vitro, but also can
      stabilize the active conformation of microbial esterases in vivo.

PMID- 16796994
TI  - Stereoselectivity of 8-OH-DPAT toward the serotonin 5-HT1A receptor: biochemical
      and molecular modeling study.
AB  - The great majority of pharmacological investigations of 5-HT1A receptors'
      reactivity has been performed using racemic 8-OH-DPAT, therefore the biochemical
      as well as behavioral profiles of both 8-OH-DPAT enantiomers are not
      circumstantiated. In the biochemical study capability of racemic 8-OH-DPAT (0.05,
      0.1 mg/kg s.c.) and its counterparts R-8-OH-DPAT (0.05, 0.1 mg/kg s.c.) and S-8
      OH-DPAT (0.05, 0.1 mg/kg s.c.) to influence 5-HT synthesis rate in rats'
      prefrontal cortex, hypothalamus, hippocampus and brainstem was evaluated by
      HPLC/ED technique. Biochemical results are supported by the exhaustive
      computational study of possible differences between R- and S-enantiomer toward
      the 5-HT1A receptor. A reliable 3D model of the rat 5-HT1A receptor was
      constructed from the amino acid sequence using the crystal structure of bovine
      rhodopsin as a structural template. The structure of the receptor model was
      validated through docking studies and molecular dynamics simulations that gave
      results consistent with experimental data. Docking studies and the dynamics of
      ligand-receptor complexes emphasized different profiles of both enantiomers at
      the molecular level. The results of both biochemical and computational studies
      confirmed that R-enantiomer in contrast to S-8-OH-DPAT acts as full and potent
      agonist, whilst racemic form may display similar pharmacological profile to R-8
      OH-DPAT.

PMID- 16796995
TI  - Neuroglobin mRNA expression after transient global brain ischemia and prolonged
      hypoxia in cell culture.
AB  - Neuroglobin is a nerve-specific respiratory protein that has been proposed to
      play an important role in the protection of brain neurons from ischemic and
      hypoxic injuries. Here, we investigated the regulation of neuroglobin expression
      after transient global ischemia in the rat brain using mRNA in situ hybridization
      and under hypoxic stress in cultured neuronal cell lines (PC12, HN33) by
      quantitative RT-PCR. While neuroglobin mRNA expression was significantly enhanced
      in cell culture after severe prolonged hypoxia (0-1% O2 for 24 h), we did not
      find any significant increases in neuroglobin mRNA levels in the rat brain after
      transient global ischemia. Vegf and Glut1 mRNAs showed increases in the
      hippocampus as expected. Therefore, it is unlikely that neuroglobin is
      instrumental in the acute response of neurons to hypoxic or ischemic insults, for
      which the mammalian brain is not adapted.

PMID- 16796996
TI  - Organization of mnemonic and response operations within prefrontal cortex.
AB  - There is mounting evidence that prefrontal cortex (PFC) is activated during
      mnemonic operations such as working memory maintenance and also during response
      related operations. In the current study, we examine the neural organization of
      mnemonic and response operations with respect to each other within PFC. Stimulus
      evoked and sustained functional MRI activity was recorded during performance of a
      mental calculation task. The presence or absence of mnemonic and response demands
      was manipulated in a 2 x 2 factorial design with conditions requiring: (1) memory
      encoding and maintenance (M+); (2) response selection and execution (R+); (3)
      encoding, maintenance, and response execution (M+R+); (4) neither mnemonic nor
      response-related processes (M-R-). The first step of the analyses identified PFC
      voxels exhibiting differential activity during (M+) vs. (R+) trials. Within these
      voxels, we then examined activity during multiple phases of (M+R+) trials.
      Greater stimulus-evoked and sustained activity was observed within the anterior
      extent of dorsolateral prefrontal cortex (BA 46) during R+ vs. M+ trials. In
      contrast, greater activity was observed in the posterior extent of dorsolateral
      PFC during M+ vs. R+ trials. Importantly, both regions were activated during
      (M+R+) trials. Activity levels during all of these conditions exceeded levels
      observed during (M-R-) control trials. These results suggest that integrative
      functions of PFC that allow past information to guide future actions may emerge
      from communication between discrete subregions supporting mnemonic and response
      operations.

PMID- 16796997
TI  - Omega-3 fatty acid effects on biochemical indices following cancer surgery.
AB  - Epidemiological studies have indicated that a high intake of saturated fat and/or
      animal fat increases the risk of colon and breast cancer. Laboratory and clinical
      investigations have shown a reduced risk of colon carcinogenesis after
      alimentation with omega-3 fatty acids, as found in fish oil. Mechanisms
      accounting for these anti-tumor effects are reduced levels of PGE(2) and
      inducible NO synthase as well as an increased lipid peroxidation, or translation
      inhibition with subsequent cell cycle arrest. Further, omega-3 eicosapentaenoic
      acid is capable of down-regulating the production and effect of a number of
      mediators of cachexia, such as IL-1, IL-6, TNF-alpha and proteolysis-inducing
      factor. In patients with advanced cancer, it is possible to increase energy and
      protein intake via an enteral or parenteral route, but this seems to have little
      impact on progressive weight loss. Fish oil administration improved patients'
      conditions in cancer cachexia and during radio- and chemotherapy. In patients
      undergoing tumor resection surgery we observed improvement of liver and pancreas
      biochemical indices when omega-3 fatty acids were administered. This paper is a
      review of recent developments in the field of nutrition in cancer patients with
      emphasis on the acute phase response following cancer surgery and the beneficial
      aspects of fish oil administration.

PMID- 16796998
TI  - Statistical morphological skull stripping of adult and infant MRI data.
AB  - This paper describes a novel automatic statistical morphology skull stripper
      (SMSS) that uniquely exploits a statistical self-similarity measure and a 2-D
      brain mask to delineate the brain. The result of applying SMSS to 20 MRI data set
      volumes, including scans of both adult and infant subjects is also described.
      Quantitative performance assessment was undertaken with the use of brain masks
      provided by a brain segmentation expert. The performance is compared with an
      alternative technique known as brain extraction tool. The results suggest that
      SMSS is capable of skull-stripping neurological data with small amounts of over-
      and under-segmentation.

PMID- 16796999
TI  - Effect of the size and location of osteochondral defects in degenerative
      arthritis. A finite element simulation.
AB  - Physiological studies have shown that focal articular surface defects in the
      human knee may progress to degenerative arthritis. Although the risk of this
      evolutive process is multifactorial, defect size is one of the most important
      factors. In order to determine the influence of osteochondral defect size and
      location on the stress and strain concentrations around the defect rim, a finite
      element model of the human knee was developed. From our results, it became clear
      that the size and location of cartilage defects drastically affect to those
      variables. No stress concentration appeared around the rim of small defects,
      being the stress distribution mainly controlled by the meniscus contact. On the
      contrary, important rim stress concentration was found for large osteochondral
      defects. This alteration of the stress distribution has important clinical
      implications regarding the long-term integrity of the cartilage adjacent to
      osteochondral defects.

PMID- 16797000
TI  - Embryonic expression profiles and conserved localization mechanisms of
      pem/postplasmic mRNAs of two species of ascidian, Ciona intestinalis and Ciona
      savignyi.
AB  - In many animals, the first cue for development is transcripts and/or proteins
      that are provided maternally and are localized at specific regions of fertilized
      eggs and early embryos. The ascidian is known to exhibit a mosaic mode of
      development, which is largely dependent on localized maternal factors. In early
      Ciona intestinalis embryos, the posterior-most localization appears to be the
      major specialized pattern of maternal transcripts. The present study examined the
      temporal and spatial expression pattern of 40 genes known as pem/postplasmic
      genes, for which maternal mRNAs are localized at the posterior-most region during
      early Ciona embryogenesis. Ten of these genes showed redistribution to B8.12-line
      cells, which are known to give rise to germ cells in ascidians. In addition 23
      orthologues were newly identified in a related ascidian species, Ciona savignyi,
      and 16 of them showed the mRNA localization pattern at the posterior-most region.
      Furthermore, the localized pattern of exogenous mRNA, which comprised the 3' UTR
      of C. intestinalis pem/postplasmic genes conjugated with the LacZ ORF, showed the
      localization at the posterior-most region in C. savignyi embryos. Likewise, the
      3' UTR of C. savignyi pem/postplasmic genes conjugated with the LacZ ORF showed
      localization at the posterior most region in C. intestinalis embryos, suggesting
      that localization mechanisms are conserved between the two species. The present
      study therefore provides basic information for future functional analyses of
      these pem/postplasmic genes and for exploring the mechanisms of localization of
      mRNAs.

PMID- 16797001
TI  - The prooxidant, rather than antioxidant, acts of daidzein in vivo and in vitro:
      daidzein suppresses glutathione metabolism.
AB  - The present study was performed to investigate the effects of chronic
      administration of daidzein on lipid peroxidation and glutathione concentration in
      the livers and brains of rats. Male Sprague-Dawley rats were divided into two
      groups, one of which was fed a normal diet and the other a vitamin E-free diet.
      Each of these groups was divided further into three subgroups and treated either
      with vehicle or with daidzein administered orally at either 2 or 20 mg/day for 4
      weeks. The concentrations of alpha-tocopherol in the serum and the brain
      increased following daidzein treatment, and these increases were significantly
      greater in rats maintained on a vitamin E-free diet. Daidzein significantly
      decreased the concentration of malondialdehyde in the organs, and this decrease
      was more pronounced in vitamin E-deprived rats than in those maintained on a
      normal diet. Although the liver glutathione concentration was not affected,
      daidzein treatment (20 mg/day) decreased the glutathione concentration in the
      brain significantly and to a similar extent in vitamin E-deprived rats and those
      fed normal diet. In addition the daidzein metabolite, equol, severely decreased
      the ratio of GSH and GSSG in primary cortical neuron cells exposed to it.
      Collectively, these results suggest that daidzein may act not only as an
      antioxidant, but also a prooxidant in brain rats, this should be in the brains of
      rats.

PMID- 16797002
TI  - Tanshinone IIA inhibits LPS-induced NF-kappaB activation in RAW 264.7 cells:
      possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways.
AB  - Nuclear factor kappaB (NF-kappaB) activation by NF-kappaB-inducing kinase (NIK)
      IkappaB alpha kinase (IKK) pathway and mitogen-activated protein kinases (MAPKs)
      pathway are important in inflammation. We recently found that the tanshinone IIA,
      a diterpene isolated from Salvia miltiorrhiza (S. miltiorrhiza), reduced the
      production of pro-inflammatory mediators in RAW 264.7 cells stimulated with
      lipopolysaccharide (LPS). However, little is known about the inhibitory
      mechanisms of tanshinone IIA on the production of pro-inflammatory mediators. To
      investigate the inhibitory mechanism, we determined the inhibitory effects of
      tanshinone IIA on the activation of NF-kappaB and IkappaB alpha phosphorylation,
      and also examined phosphorylation of NIK and IKK as well as the activation of
      MAPKs such as p38 MAPK (p38), extracellular signal-regulated kinases 1/2
      (ERK1/2), and c-Jun N-terminal kinase (JNK) in RAW 264.7 cells stimulated with
      LPS. Tanshinone IIA inhibited NF-kappaB-DNA complex, NF-kappaB binding activity,
      and the phosphorylation of IkappaB alpha in a dose dependent manner. Tanshinone
      IIA also inhibited the translocation of NF-kappaB from cytosol to nucleus.
      Moreover, the phosphorylation of NIK and IKK as well as the phosphorylation of
      p38, ERK1/2, and JNK in the LPS-stimulated RAW 264.7 cells were suppressed by the
      tanshinone IIA in a dose dependent manner. These results suggest that tanshinone
      IIA may inhibit LPS-induced IkappaB alpha degradation and NF-kappaB activation
      via suppression of the NIK-IKK pathway as well as the MAPKs (p38, ERK1/2, and
      JNK) pathway in RAW 264.7 cells and these properties may provide a potential
      mechanism that explains the anti-inflammatory activity of tanshinone IIA.

PMID- 16797003
TI  - Attenuation of opioid tolerance by antisense oligodeoxynucleotides targeting
      neurogranin.
AB  - Neurogranin is capable of regulating protein kinase C and Ca2+/calmodulin
      dependent protein kinase II. In this study, we examined the role of neurogranin
      in opioid tolerance. Increased phosphorylation of neurogranin was found in opioid
      tolerance. Opioid tolerance was absent in morphine (100 mg/kg)-treated mice that
      were also pretreated with neurogranin antisense oligodeoxynucleotides (2
      microg/day, i.c.v. for 3 days). The behavioral effect correlated with the
      decreased expression of neurogranin. These data suggest that neurogranin may be
      critical in the development of opioid tolerance.

PMID- 16797004
TI  - N-[2-(m-methoxyphenyl)ethyl]-N-ethyl-2-(1-pyrrolidinyl)ethylamine (UMB 116) is a
      novel antagonist for cocaine-induced effects.
AB  - Previous research has shown that sigma receptors participate in the actions of
      cocaine in the body. This has led to investigations of the use of novel agents
      such as BD1008, BD1067 and YZ-011 as cocaine antagonists. In the present study,
      three novel analogs (UMB115, UMB116, UMB117), representing composites of these
      earlier compounds, were evaluated in receptor binding and behavioral studies. In
      the receptor binding studies, the compounds were shown to have high affinity for
      sigma receptors and much lower affinities for non-sigma sites. For the behavioral
      experiments, Swiss Webster mice were pre-treated with saline or one of the novel
      compounds (0.1-10 mg/kg), followed 15 min later by a convulsive (60 mg/kg),
      lethal (125 mg/kg), or locomotor stimulatory (10 mg/kg) dose of cocaine. The
      results showed that UMB115, UMB116 and UMB117 significantly (P<0.05) inhibited
      cocaine-induced convulsions when administered as a pre-treatment to cocaine.
      Cocaine-induced lethality was significantly attenuated by UMB116 (P<0.05), but
      not by UMB115 and UMB117. All three compounds significantly (P<0.05) altered the
      locomotor stimulatory effects of cocaine, with UMB115 and UMB116 exhibiting
      attenuating actions. Together, the studies suggest UMB116 as a novel cocaine
      antagonist.

PMID- 16797005
TI  - Inhibitory effect of chroman carboxamide on interleukin-6 expression in response
      to lipopolysaccharide by preventing nuclear factor-kappaB activation in
      macrophages.
AB  - 6-Hydroxy-7-methoxychroman-2-carboxylic acid (3-nitrophenyl)amide (CP-1158) is a
      synthetic chroman carboxamide with trolox-like chemical structure. In the present
      study, CP-1158 was found to inhibit interleukin (IL)-6 production in
      lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. The CP-1158 attenuated
      LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6
      promoter activity. Further, CP-1158 attenuated LPS-induced syntheses of tumor
      necrosis factor (TNF)-alpha, IL-1beta, interferon-inducible protein (IP)-10 and
      macrophage inflammatory protein (MIP)-1beta transcripts. Nuclear factor (NF)
      kappaB has been evidenced to play a major mechanism in LPS-induced expression of
      IL-6 or other inflammatory cytokines. CP-1158 prevented LPS-induced nuclear
      translocation of NF-kappaB complex and subsequently inhibited DNA binding
      activity of NF-kappaB complex as well as NF-kappaB transcriptional activity in
      macrophages RAW 264.7. However, CP-1158 did not affect LPS-induced
      phosphorylation and degradation of inhibitory kappaB (IkappaB). In another
      experiment, CP-1158 inhibited IL-6 promoter activity elicited by expression
      vectors encoding NF-kappaB p50 or p65 subunit. Taken together, CP-1158 inhibited
      LPS-induced expression of inflammatory cytokines including IL-6, targeting NF
      kappaB activating pathway downstream IkappaB degradation, and thus could provide
      an anti-inflammatory potential of chroman carboxamide.

PMID- 16797006
TI  - Aqueous flow in galactose-fed dogs.
AB  - Dogs fed galactose develop diabetes-like ocular complications that include
      keratopathy, cataracts, and retinopathy. The purpose of this study was to
      investigate whether galactosemic dogs display reduced aqueous flow similar to
      that observed in patients with insulin-dependent diabetes mellitus. Twelve male
      beagles at 9 months of age were divided into three groups of four. The Galactose
      group was fed diet containing 30% galactose for 97 months and the Reversal group
      was fed the galactose diet for an initial 38 months then standard dog diet for
      the remaining period. The Control group was fed standard dog diet for 97 months.
      Aqueous flow was determined by fluorophotometry in one eye per dog at 96 and 97
      months after the initiation of galactose feeding. Intraocular pressure (IOP) was
      measured once in the morning by pneumatonometry. Anterior chamber depth was
      measured by A-scan. At the end of the experiment, eyes were enucleated and
      processed for histological examination. Dogs fed galactose diet for 97 months had
      significantly (p<0.05) increased body weights but similar IOP and anterior
      chamber depth compared to the other groups, and significantly (p=0.05) reduced
      aqueous flow compared to the control group (4.4+/-2.2 vs. 6.8+/-2.4 microl/min,
      mean+/-standard deviation, respectively). Additionally, aqueous flow decreased in
      the Reversal group to 3.1+/-1.3 microl/min (p=0.002). This decrease correlated
      with morphological changes of the ciliary processes. Like patients with insulin
      dependent diabetes mellitus, galactose-fed dogs demonstrate reduced aqueous flow.
      This reduction was irreversible and independent of the retinopathy present. This
      animal model may be useful for the study of aqueous humor dynamics in diabetes.

PMID- 16797007
TI  - ALDH3A1: a corneal crystallin with diverse functions.
AB  - Aldehyde dehydrogenase 3A1 (ALDH3A1) comprises a surprisingly high proportion (5
      50% depending on species) of the water-soluble protein of the mammalian cornea,
      but is present little if at all in the cornea of other species. Mounting
      experimental evidence demonstrates that this abundant corneal protein plays an
      important role in the protection of ocular structures against oxidative damage.
      Corneal ALDH3A1 appears to protect against UV-induced oxidative stress through a
      variety of biological functions such as the metabolism of toxic aldehydes
      produced during the peroxidation of cellular lipids, the generation of the
      antioxidant NADPH, the direct absorption of UV-light, the scavenging of reactive
      oxygen species (ROS), and the possession of chaperone-like activity. With
      analogies to the abundant, multifunctional, and taxon-specific lens crystallins,
      mammalian ALDH3A1 has been considered a corneal crystallin, suggesting that it
      may contribute to the optical properties of the cornea as well. Recent studies
      have also revealed a novel role for ALDH3A1 in the regulation of the cell cycle.
      ALDH3A1-transfected HCE cells have increased population-doubling time, decreased
      plating efficiency, and reduced DNA synthesis, most likely due to a profound
      inhibition of cyclins and cyclin-dependent kinases. We have proposed that the
      ALDH3A1-induced reduction in cell growth may contribute to protection against
      oxidative stress by extending time for DNA and cell repair. Taken together, the
      multiple roles of ALDH3A1 against oxidative stress in addition to its
      contributions to the optical properties of the cornea are consistent with the
      idea that this specialized protein performs diverse biological functions as do
      the lens crystallins.

PMID- 16797008
TI  - Plasmodium falciparum: worldwide sequence diversity and evolution of the malaria
      vaccine candidate merozoite surface protein-2 (MSP-2).
AB  - We examined patterns and putative mechanisms of sequence diversification in the
      merozoite surface protein-2 (MSP-2) of Plasmodium falciparum, a major dimorphic
      malaria vaccine candidate antigen, by analyzing 448 msp-2 alleles from all
      continents. We describe several nucleotide replacements, insertion and deletion
      events, frameshift mutations, and proliferations of repeat units that generate
      the extraordinary diversity found in msp-2 alleles. We discuss the role of
      positive selection exerted by naturally acquired type- and variant-specific
      immunity in maintaining the observed levels of polymorphism and suggest that this
      is the most likely explanation for the significant excess of nonsynonymous
      nucleotide replacements found in dimorphic msp-2 domains. Hybrid sequences
      created by meiotic recombination between alleles of different dimorphic types
      were observed in few (3.1%) isolates, mostly from Africa. We found no evidence
      for an extremely ancient origin of allelic dimorphism at the msp-2 locus,
      predating P. falciparum speciation, in contrast with recent findings for other
      surface malarial antigens.

PMID- 16797010
TI  - Lipid imbalance in the neurological disorder, Niemann-Pick C disease.
AB  - Niemann-Pick C (NPC) disease is a progressive neurological disorder in which
      cholesterol, gangliosides and bis-monoacylglycerol phosphate accumulate in late
      endosomes/lysosomes. This disease is caused by mutations in either the NPC1 or
      NPC2 gene. NPC1 and NPC2 are involved in egress of lipids, particularly
      cholesterol, from late endosomes/lysosomes but the precise functions of these
      proteins are not clear. An important question regarding the function of NPC
      proteins is: why do mutations in these ubiquitously expressed proteins have such
      dire consequences in the brain? This review summarizes the roles of NPC proteins
      in lipid homeostasis particularly in the central nervous system.

PMID- 16797009
TI  - A novel function for a ubiquitous plant enzyme pectin methylesterase: the
      enhancer of RNA silencing.
AB  - Co-agroinjection of Nicotiana benthamiana leaves with the pectin methylesterase
      (proPME) gene and the TMV:GFP vector resulted in a stimulation of virus-induced
      RNA silencing (inhibition of GFP production, virus RNA degradation, stimulation
      of siRNAs production). Conversely, co-expression of TMV:GFP with either antisense
      PME construct or with enzymatically inactive proPME restored synthesis of viral
      RNA. Furthermore, expression of proPME enhanced the GFP transgene-induced gene
      silencing accompanied by relocation of the DCL1 protein from nucleus to the
      cytoplasm and activation of siRNAs and miRNAs production. It was hypothesized
      that DCL1 relocated to the cytoplasm may use as substrates both miRNA precursor
      and viral RNA. The capacity for enhancing the RNA silencing is a novel function
      for the polyfunctional PME.

PMID- 16797011
TI  - Mapping the essential structures of human ribosomal protein L7 for nuclear entry,
      ribosome assembly and function.
AB  - Human large subunit protein L7 carries multiple nuclear localization signals
      (NLS) in its structure: there are three monobasic partite NLSs at the NH2-region
      of the first 54 amino acid residues and a bipartite in the middle section at
      position of 156-167. The C-region of the last 50 amino acid residues displays
      membrane binding nature, and might involve in forming a nuclear microbody for pre
      nucleolar ribosome assembly. The middle section covers 144 amino acid residues
      which are essential for the structure and function of ribosome. This is evident
      from findings that truncated L7 without the NH2-region or the C-region, or
      missing both regions, is capable of reaching nucleolus and incorporating in
      ribosome, however, only ribosomes bearing truncated L7 without the NH2-region is
      capable of engaging in polysome formation. Combining with the phylogenic findings
      from homologous sequence alignment, the NH2-region of L7, besides being as a
      eukaryotic expansion segment, can be excluded from building a functional
      eukaryotic ribosome.

PMID- 16797012
TI  - Blue news: NTP binding properties of the blue-light sensitive YtvA protein from
      Bacillus subtilis.
AB  - The blue-light sensitive protein YtvA from Bacillus subtilis is built of a
      photoactive, flavin-binding LOV (Light, Oxygen and Voltage) domain and a STAS
      domain with unknown function. Here we show that YtvA binds a fluorescent
      derivative of guanosine triphosphate (GTPTR) that can be displaced by both GTP or
      ATP. Unspecific NTP (N=G or A) binding is supported by the molecular model of
      YtvA-STAS. Blue-light activation of YtvA results in small and dark-reversible
      spectroscopic changes for GTPTR, suggesting that light-driven conformational
      changes are transmitted from the LOV core to the GTPTR binding site. These
      results support the idea that STAS domains may have a general NTP binding role
      and open a way to investigate the molecular functionality of YtvA-STAS.

PMID- 16797014
TI  - Temperature adaptation of synonymous codon usage in different functional
      categories of genes: a comparative study between homologous genes of
      Methanococcus jannaschii and Methanococcus maripaludis.
AB  - Synonymous codon usage of homologous sequences between Methanococcus jannaschii
      and Methanococcus maripaludis have been analyzed in three broad functional
      categories of genes namely: (i) information storage and processing; (ii)
      metabolism; and (iii) cellular processes and signaling. Average values of
      synonymous nucleotide substitutions per synonymous site are significantly lower
      for information processing genes compared to either metabolic or cellular
      processing genes. These results suggests that synonymous codon usage has been
      subject to greater constraint in the information storage and processing group of
      genes compared to other functional categories of genes. For metabolic and
      cellular processing genes, correspondence analysis based on relative synonymous
      codon usage (RSCU) values separates the genes along the first major axes
      according to the genome type; while in the information processing group, genes
      are separated along the second major axes according to the genome type. Further
      study on synonymous substitution rate for information processing genes shows a
      stronger selective constraint on synonymous codon usage of six amino acids,
      G,A,R,P,Y,F. Randomization of the original transcript of M. jannaschii for
      information processing genes suggests that variation in selective constraint
      between synonymous codon usage is related to the potential formation of mRNA
      secondary structures which contribute to the folding stability.

PMID- 16797013
TI  - Impact of intra-subunit domain-domain interactions on creatine kinase activity
      and stability.
AB  - Creatine kinase (CK) is a key enzyme in vertebrate excitable tissues. In this
      research, five conserved residues located on the intra-subunit domain-domain
      interface were mutated to explore their role in the activity and structural
      stability of CK. The mutations of Val72 and Gly73 decreased both the activity and
      stability of CK. The mutations of Cys74 and Val75, which had no significant
      effect on CK activity and structure, gradually decreased the stability and
      reactivation of CK. Our results suggested that the mutations might modify the
      correct positioning of the loop contributing to domain-domain interactions, and
      result in decreased stability against denaturation.

PMID- 16797015
TI  - Acute oxidative stress is associated with cell proliferation in the mouse liver.
AB  - Oxidative stress is known to produce tissue injury and to activate various
      signaling pathways. To investigate the molecular events linked to acute oxidative
      stress in mouse liver, we injected a toxic dose of paraquat. Liver necrosis was
      first observed, followed by histological marks of cell proliferation.
      Concomitantly, activation of the MAP kinase pathway and increased levels of the
      anti-apoptotic protein Bcl-XL were observed. Gene expression profiles revealed
      that the differentially expressed genes were potentially involved in cell
      proliferation. These data suggest that paraquat-induced acute oxidative stress
      triggers the activation of regeneration-related events in the liver.

PMID- 16797016
TI  - Alg44, a unique protein required for alginate biosynthesis in Pseudomonas
      aeruginosa.
AB  - Here the putative alginate biosynthesis gene alg44 of Pseudomonas aeruginosa was
      functionally assigned. Non-polar isogenic alg44 deletion mutants of P. aeruginosa
      were generated and did neither produce alginate nor released free uronic acids.
      No evidence for alginate enrichment in the periplasm was obtained. Alginate
      production was restored by introducing only the gene alg44. PhoA fusion protein
      analyses suggested that Alg44 is a soluble protein localized in the periplasm.
      Hexahistidine-tagged Alg44 was detected by immunoblotting. The corresponding 42.6
      kDa protein was purified and identified by MALDI/TOF-MS analysis. Alg44 might be
      directly involved in alginate polymerization presumably by exerting a regulatory
      function.

PMID- 16797018
TI  - A comparative cross-sectional questionnaire survey of the work of UK and US
      mental health nurses.
AB  - BACKGROUND: Comparative inter-country research which identifies similarities and
      differences in the work of mental health nurses in different social and political
      contexts is an important means of determining how changes in health care systems
      could lead to better outcomes for patients. OBJECTIVE: This study sought to
      compare aspects of the work of nurses in US and UK mental health care settings.
      Nurses were invited to reflect on aspects of their role including identifying the
      most and least satisfying elements of their work and suggesting ways in which it
      could be improved. METHODS AND PARTICIPANTS: A 12-item questionnaire, comprising
      closed and open-ended questions, based on the literature and the authors' own
      experiences of mental health nursing practice, was piloted and subsequently
      distributed to respondents in both countries. RESULTS: The US nurses tended to be
      more willing to accept a wider range of clients than their UK counterparts,
      although they had lower expectations of their clients' likelihood of recovery.
      Both groups of nurses felt that being part of a team and having direct contact
      with clients were the most satisfying aspects of their work, while administration
      was the least. Although both US and UK nurses utilised a variety of intervention
      models, it would appear that Cognitive Behavioural Therapy was the favoured model
      for the majority of nurses. CONCLUSIONS: The implications of these findings for
      the work of nurses and mental health care services in the UK and US, and the
      purpose, nature and need for future international comparative research are
      discussed.

PMID- 16797020
TI  - A volumetric model for growth of arterial walls with arbitrary geometry and
      loads.
AB  - Stress and deformation in arterial wall tissue are factors which may influence
      significantly its response and evolution. In this work we develop models based on
      nonlinear elasticity and finite element numerical solutions for the mechanical
      behaviour and the remodelling of the soft tissue of arteries, including
      anisotropy induced by the presence of collagen fibres. Remodelling and growth in
      particular constitute important features in order to interpret stenosis and
      atherosclerosis. The main object of this work is to model accurately volumetric
      growth, induced by fluid shear stress in the intima and local wall stress in
      arteries with patient-specific geometry and loads. The model is implemented in a
      nonlinear finite element setting which may be applied to realistic 3D geometries
      obtained from in vivo measurements. The capabilities of this method are
      demonstrated in several examples. Firstly a stenotic process on an idealised
      geometry induced by a non-uniform shear stress distribution is considered.
      Following the growth of a right coronary artery from an in vivo reconstructed
      geometry is presented. Finally, experimental measurements for growth under
      hypertension for rat carotid arteries are modelled.

PMID- 16797019
TI  - The varying microsporidian genome: existence of long-terminal repeat
      retrotransposon in domesticated silkworm parasite Nosema bombycis.
AB  - Microsporidia are a group of intracellular parasites with an extremely compact
      genome and there is no confirmed evidence that retroelements are parasitised in
      these organisms. Using the dataset of 200,000 genomic shotgun reads of the
      silkworm pebrine Nosema bombycis, we have identified the eight complete N.
      bombycis long-terminal repeat retrotransposon (Nbr) elements. All of the Nbr
      elements are Ty3/gypsy members and have close relationships to Saccharomycetes
      long-terminal repeat retrotransposons identified previously, providing further
      evidence of their relationship to fungi. To explore the effect of
      retrotransposons in microsporidian genome evolution, their distribution was
      characterised by comparisons between two N. bombycis contigs containing the Nbr
      elements with the completed genome of the human parasite Encephalitozoon
      cuniculi, which is closely related to N. bombycis. The Nbr elements locate
      between or beside syntenic blocks, which are often clustered with other
      transposable-like sequences, indicating that they are associated with genome size
      variation and syntenic discontinuities. The ratios of the number of non
      synonymous substitutions per non-synonymous site to the number of synonymous
      substitutions per synonymous site of the open reading frames among members of
      each of the eight Nbr families were estimated, which reveal the purifying
      selection acted on the N. bombycis long-terminal repeat retrotransposons. These
      results strongly suggest that retrotransposons play a major role in
      reorganization of the microsporidian genome and they might be active. The present
      study presents an initial characterization of some transposable elements in the
      N. bombycis genome and provides some insight into the evolutionary mechanism of
      microsporidian genomes.

PMID- 16797021
TI  - The effect of coordinate system choice and segment reference on RSA-based knee
      translation measures.
AB  - Roentgen stereophotogrammetric analysis (RSA) can be utilized to accurately
      describe joint kinematics, but even when measuring small displacements within
      radiographically discernible structures, standardized reference frames are
      imperative for useful comparison across patients and across studies. In the
      current paper, accurately controlled laboratory models demonstrated the
      considerable influence that a mere 1.9-cm offset of the origin of the coordinate
      system from the rotation axes could exert on translation measures when rotations
      were occurring. In addition, the use of two different coordinate systems to gauge
      translation on a radiographic anterior-posterior (A-P) knee laxity exam resulted
      in a significant correlation (R(2)=0.562) between the two systems; however,
      differences of up 9.28 mm were found between corresponding measurements. This
      implies that clinical conclusions can potentially be upheld or refuted, based on
      the same data set, subject to coordinate system definition. Although the data
      analyzed presently involved the knee joint, similar issues surround the RSA
      motion analysis of other joints as well.

PMID- 16797022
TI  - In vitro simulations of embryo transfer in a laboratory model of the uterus.
AB  - Embryo transfer (ET) is the final manual intervention during which the newly
      formed embryo is placed within the uterus by a transcervical catheter. The
      loading of the syringe-catheter complex with the transferred volume consists of
      the transfer media (which contains the embryos) separated by air spaces on both
      sides. The dynamics involved in injecting the syringe-catheter complex is not
      well understood nor has it been investigated to date. We developed an in vitro
      experimental setup for simulations of ET into a rigid transparent uterine model.
      The catheter was loaded in sequences of liquid and air as it is in the clinical
      setting. The transferred liquid was colored with a dye and its dispersion within
      the uterine cavity was recorded by a video camera. The results demonstrated, for
      the first time, the importance of having a gas phase in the catheter load. The
      resulting air bubbles within the uterus were carried upward towards the fundus by
      buoyant forces, thereby dragging behind them the transferred liquid which
      contained the embryos. This could be expected to substantially increase the
      probability for the embryos to be present near the fundal wall at the time window
      for implantation. There was also evidence of a dependency of the rate of
      injection upon the catheter load into the uterus: a low speed generated several
      air bubbles which led to more of the transferred liquid being carried towards the
      fundal end, thus possibly enhancing the potential for implantation.

PMID- 16797023
TI  - Experimental verification of a computational technique for determining ground
      reactions in human bipedal stance.
AB  - We have developed a three-dimensional (3D) biomechanical model of human standing
      that enables us to study the mechanisms of posture and balance simultaneously in
      various directions in space. Since the two feet are on the ground, the system
      defines a kinematically closed-chain which has redundancy problems that cannot be
      resolved using the laws of mechanics alone. We have developed a computational
      (optimization) technique that avoids the problems with the closed-chain
      formulation thus giving users of such models the ability to make predictions of
      joint moments, and potentially, muscle activations using more sophisticated
      musculoskeletal models. This paper describes the experimental verification of the
      computational technique that is used to estimate the ground reaction vector
      acting on an unconstrained foot while the other foot is attached to the ground,
      thus allowing human bipedal standing to be analyzed as an open-chain system. The
      computational approach was verified in terms of its ability to predict lower
      extremity joint moments derived from inverse dynamic simulations performed on
      data acquired from four able-bodied volunteers standing in various postures on
      force platforms. Sensitivity analyses performed with model simulations indicated
      which ground reaction force (GRF) and center of pressure (COP) components were
      most critical for providing better estimates of the joint moments. Overall, the
      joint moments predicted by the optimization approach are strongly correlated with
      the joint moments computed using the experimentally measured GRF and COP (0.78 <
      or = r(2) < or = 0.99,median,0.96) with a best-fit that was not statistically
      different from a straight line with unity slope (experimental=computational
      results) for postures of the four subjects examined. These results indicate that
      this model-based technique can be relied upon to predict reasonable and
      consistent estimates of the joint moments using the predicted GRF and COP for
      most standing postures.

PMID- 16797025
TI  - The interplay between perceptual organization and categorization in the
      representation of complex visual patterns by young infants.
AB  - The relation between perceptual organization and categorization processes in 3-
      and 4-month-olds was explored. The question was whether an invariant part
      abstracted during category learning could interfere with Gestalt organizational
      processes. A 2003 study by Quinn and Schyns had reported that an initial category
      familiarization experience in which infants were presented with visual patterns
      consisting of a pacman shape and a complex polygon could interfere with infants'
      subsequent good continuation-based parsing of a circle from visual patterns
      consisting of a circle and a complex polygon. However, an alternative
      noninterference explanation for the results was possible because the pacman had
      been presented with greater frequency and duration than had the circle. The
      current study repeated Quinn and Schyns's procedure but provided an equivalent
      number of familiarization trials and duration of study time for the infants to
      process the pacman during initial familiarization and the circle during
      subsequent familiarization. The results replicated the previous findings of Quinn
      and Schyns. The data are consistent with the interference account and suggest
      that a cognitive system of adaptable feature creation can take precedence over
      organizational principles with which a perceptual system comes pre-equipped.

PMID- 16797024
TI  - Effect of tetraalkylammonium salts on retention of betacyanins and decarboxylated
      betacyanins in ion-pair reversed-phase high-performance liquid chromatography.
AB  - The ability of tetraalkylammonium salts to act as ion-pairing agents for
      betacyanins and mono- as well as bidecarboxylated betacyanins in HPLC on reversed
      phase is reported. The results indicate substantial and various influences of
      tetraalkylammonium salt addition to eluent on magnitude and direction of
      retention time changes of the analytes. The interactions of the
      tetraalkylammonium cations with the accessible positive and negative charged
      parts of the analysed molecules at their different level and position of
      decarboxylation determined the possibility of ion-pair formation. A remarkable
      positive influence was observed for betacyanins on the basis of strongly enhanced
      retention of the resulted ion-pairs. In contrast, the 2,17-bidecarboxy-betacyanin
      retention, in most of the applied conditions, strongly decreased under the impact
      of the reagents. The effect of the salt concentration on direction of 17
      decarboxy-betacyanin and 2,17-bidecarboxy-betacyanin retention changes strongly
      varied with the eluent pH. The carboxylic group at the C-2 carbon cannot interact
      with tetraalkylammonium cations as strongly as does the C-17 carboxylic group,
      leading to different effects in the absence of carboxylic group at the C-2 or C
      17 carbon in the molecules.

PMID- 16797026
TI  - Electrochemical and piezoelectric quartz crystal detection of antisperm antibody
      based on protected Au nanoparticles with a mixed monolayer for eliminating
      nonspecific binding.
AB  - The detection of antisperm antibody (AsAb) by electrochemical method based on Au
      nanoparticles with a mixed monolayer for eliminating nonspecific binding is
      presented. Impedance spectroscopy is used to characterize the modified
      procedures, the immobilization of sperm antigen (SpAg) and binding of AsAb in the
      presence of [Fe (CN)(6)](3-/4-). In addition, piezoelectric quartz crystal, PQC,
      was used to analyze the immobilization quantity of Au nanoparticles as well as to
      optimize experimental conditions. The change of electron-transfer resistance was
      correlated with the concentration of AsAb in a range from 25 to 600 mU/ml with
      the detection limit of 10 mU/ml. The analytical results of several human serum
      samples using the developed technique are in satisfactory agreement with those
      given by the enzyme-linked immunosorbent assay (ELISA) method.

PMID- 16797027
TI  - Interplay between ion binding and catalysis in the thioredoxin-coupled arsenate
      reductase family.
AB  - In the thioredoxin (Trx)-coupled arsenate reductase family, arsenate reductase
      from Staphylococcus aureus plasmid pI258 (Sa_ArsC) and from Bacillus subtilis
      (Bs_ArsC) are structurally related detoxification enzymes. Catalysis of the
      reduction of arsenate to arsenite involves a P-loop
      (Cys10Thr11Gly12Asn13Ser14Cys15Arg16) structural motif and a disulphide cascade
      between three conserved cysteine residues (Cys10, Cys82 and Cys89). For its
      activity, Sa_ArsC benefits from the binding of tetrahedral oxyanions in the P
      loop active site and from the binding of potassium in a specific cation-binding
      site. In contrast, the steady-state kinetic parameters of Bs_ArsC are not
      affected by sulphate or potassium. The commonly occurring mutation of a histidine
      (H62), located about 6 A from the potassium-binding site in Sa_ArsC, to a
      glutamine uncouples the kinetic dependency on potassium. In addition, the binding
      affinity for potassium is affected by the presence of a lysine (K33) or an
      aspartic acid (D33) in combination with two negative charges (D30 and E31) on the
      surface of Trx-coupled arsenate reductases. In the P-loop of the Trx-coupled
      arsenate reductase family, the peptide bond between Gly12 and Asn13 can adopt two
      distinct conformations. The unique geometry of the P-loop with Asn13 in beta
      conformation, which is not observed in structurally related LMW PTPases, is
      stabilized by tetrahedral oxyanions and decreases the pK(a) value of Cys10 and
      Cys82. Tetrahedral oxyanions stabilize the P-loop in its catalytically most
      active form, which might explain the observed increase in k(cat) value for
      Sa_ArsC. Therefore, a subtle interplay of potassium and sulphate dictates the
      kinetics of Trx-coupled arsenate reductases.

PMID- 16797028
TI  - Quality of life and depression in Parkinson's disease.
AB  - This paper reviews the literature on health-related quality of life (Hr-QoL) and
      depressive disorders, and the relationship between them, in patients with
      Parkinson's disease (PD). PD is associated with reduced Hr-QoL, including motor
      and non-motor physical consequences of the disease, emotional well-being and
      social functioning. While this effect is greater in advanced disease stages,
      there is no close relationship between disease duration and impact on quality of
      life, and the relationship between clinical rating scales and Hr-QoL scores is
      only moderate. On the other hand, presence and severity of depression in PD
      strongly correlates with Hr-QoL scores, and a number of studies have reported
      depression as the main determinant of poor HR-QoL scores. Despite being the main
      determinant of poor Hr-QoL and being recognized as an important problem by
      clinicians, until recently depression in PD has received relatively little
      attention in research studies. It is known that depression and anxiety occur more
      frequently in PD than in controls. Depression occurs in a bimodal pattern in PD,
      with increased rates at the onset and a later peak in advanced disease. Both
      anxiety and depression can also occur before the first motor symptoms of PD and
      predate the diagnosis of PD, indicating that these co-morbidities are
      manifestations of the underlying disease process of PD. Imaging studies have
      demonstrated abnormalities of dopaminergic, noradrenergic and serotonergic
      functioning with some correlation with severity of depression. The overall
      relationship between disease severity and rate of depression (except for off
      period related depression) is poor, suggesting that nigrostriatal dysfunction
      alone is not sufficient to explain depressive symptoms in PD. Other factors are
      likely to contribute to occurrence and severity of depression in PD, either due
      to extrastriatal pathology or due to psychological and environmental factors
      leading to reactive depression. Thus, it is likely that depression in PD is
      multifactorial. The investigation of depression in PD is complicated by
      diagnostic difficulties in measuring and diagnosing depression in patients with
      PD due to the considerable overlap between symptoms of PD and depression. While a
      number of treatment approaches have been suggested, double-blind randomized
      controlled trials to demonstrate improvement of depression and overall Hr-QoL in
      PD are warranted.

PMID- 16797029
TI  - Iron and ferritin in hippocampal cortex and substantia nigra in human brain-
      implications for the possible role of iron in dementia.
AB  - The concentrations of iron and of ferritin, the main iron-binding compound in the
      brain, as well as the sizes of the iron cores of ferritin were assessed in
      hippocampal cortex (Hip) and substantia nigra (SN) from human control brains,
      using Mossbauer spectroscopy (MS), ELISA and electron microscopy. 8 Hip and 20 SN
      samples were measured by MS, 11 Hip and 11 SN were used for ELISA, and the size
      of the iron cores of ferritin was assessed from measurements of 50 iron cores
      from Hip-ferritin and 50 iron cores from SN-ferritin. The average concentration
      of iron in Hip was found to be about one third of that in SN, as was the
      concentration of H-ferritin, yet L-ferritin was less than one fifth in Hip
      compared to SN. The size of the average iron core in Hip was assessed to be about
      3.1 nm and about 3.7 nm in SN. These results may point to different iron
      metabolism in these areas, suggesting faster iron turnover in Hip.

PMID- 16797030
TI  - The effect of differential survivorship on the stability of reproductive
      queueing.
AB  - Queues, in which individuals inherit resources in a predictable, temporally
      stable order, are widespread in animal social groups. We develop an analytic
      model to explore the effect of differential survivorship on the stability of a
      reproductive queue. We show that unless fighting for dominance is potentially
      fatal, future direct benefits are not alone sufficient to stabilize a queue of
      non-relatives under constant (age-independent) mortality rates, regardless of
      whether a dominant becomes an isolate or remains a dominant on the death of the
      first subordinate. In the absence of fatal fighting, stabilization of such a
      queue by future direct benefits alone requires either the dominant or the
      subordinate to have age-dependent mortality rates. Even when the queue is
      stabilized by present direct reproduction, however, the shape of the lifespan
      distribution can make a significant difference to the size of the required
      incentive. In contrast to non-relatives, queues of relatives can be stable
      without age-dependent mortality, so long as relatedness exceeds a critical value;
      however, age-dependent mortality can lower this critical value.

PMID- 16797031
TI  - The prey-dependent consumption two-prey one-predator models with stage structure
      for the predator and impulsive effects.
AB  - In this paper, we consider the prey-dependent consumption two-prey one-predator
      models with stage structure for the predator and impulsive effects. By applying
      the Floquet theory of linear periodic impulsive equation, we show that there
      exists a globally asymptotically stable pest-eradication periodic solution when
      the impulsive period is less than some critical value, that is, the pest
      population can be eradicated totally. But from the point of ecological balance
      and saving resources, we only need to control the pest population under the
      economic threshold level instead of eradicating it totally, and thus, we further
      prove that the system is uniformly permanent if the impulsive period is larger
      than some critical value, and meanwhile we also give the conditions for the
      extinction of one of the two preys and permanence of the remaining species. Thus,
      we can use the stability of the positive periodic solution and its period to
      control insect pests at acceptably low levels. Considering population communities
      always are imbedded in periodically varying environments, and the parameters in
      ecosystem models may oscillate simultaneously with the periodically varying
      environments, we add a forcing term into the prey population's intrinsic growth
      rate. The resulting bifurcation diagrams show that with the varying of
      parameters, the system experiences process of cycles, periodic windows, periodic
      doubling cascade, symmetry breaking bifurcation as well as chaos.

PMID- 16797032
TI  - Cellular action of cholecystokinin-8S-mediated excitatory effects in the rat
      periaqueductal gray.
AB  - The peptide cholecystokinin (CCK) is one of the major neurotransmitters
      modulating satiety, nociception, and anxiety behavior. Although many behavioral
      studies showing anti-analgesic and anxiogenic actions of CCK have been reported,
      less is known about its cellular action in the central nervous system (CNS).
      Therefore, we examined the action of CCK in rat dorsolateral periaqueductal gray
      (PAG) neurons using slice preparations and whole-cell patch-clamp recordings.
      Application of CCK-8S produced an inward current accompanied by increased
      spontaneous synaptic activities. The CCK-8S-induced inward current (I(CCK)) was
      recovered after washout and reproduced by multiple exposures. Current-voltage
      plots revealed that I(CCK) reversed near the equilibrium potential for K(+) ions
      with a decreased membrane conductance. When several K(+) channel blockers were
      used, application of CdCl(2), TEA, or apamin significantly reduced I(CCK). I(CCK)
      was also significantly reduced by the CCK(2) receptor antagonist, L-365,260,
      while it was not affected by the CCK(1) receptor antagonist, L-364,718.
      Furthermore, we examined the effects of CCK-8S on miniature excitatory
      postsynaptic currents (mEPSCs) in order to determine the mechanism of CCK
      mediated increase on synaptic activities. We found that CCK-8S increased the
      frequency of mEPSCs, but had no effect on mEPSC amplitude. This presynaptic
      effect persisted in the presence of CdCl(2) or Ca(2+)-free bath solution, but was
      completely abolished by pre-treatment with BAPTA-AM, thapsigargin or L-365,260.
      Taken together, our results indicate that CCK can excite PAG neurons at both pre-
      and postsynaptic loci via the activation of CCK(2) receptors. These effects may
      be important for the effects of CCK on behavior and autonomic function that are
      mediated via PAG neurons.

PMID- 16797034
TI  - Reliably estimating the effect of toxicants on fertilization success in marine
      broadcast spawners.
AB  - Recently, there has been a dramatic increase in the number of ecotoxicological
      studies examining the effects of toxicants on fertilization success in marine
      broadcast spawners and it appears that this life-history stage is one of the most
      vulnerable to toxicants. Most of the studies examining this issue use single
      sperm concentrations in their assays. Here, I discuss recent advances in
      fertilization ecology that suggest this technique has some severe limitations
      resulting in unreliable estimations of the size and direction of toxicant
      effects. I present an alternative assay technique and two metrics (F(max) and
      [Sperm](max)) that will reliably estimate the size of a toxicant's effect on
      fertilization success. This technique has the added advantage of making
      comparisons among species and studies easier without an impractical increase in
      effort.

PMID- 16797033
TI  - Effect of berberrubine on interleukin-8 and monocyte chemotactic protein-1
      expression in human retinal pigment epithelial cell line.
AB  - We examined the effects of berberrubine, a protoberberine alkaloid, on
      interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) expression in a
      human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin
      1beta (IL-1beta) or tumor necrosis factor alpha (TNF-alpha). ARPE-19 cells were
      cultured to confluence. Berberrubine and IL-1beta or TNF-alpha were added to the
      medium. IL-8 and MCP-1 protein concentrations were measured using enzyme-linked
      immunosorbent assay. IL-8 and MCP-1 mRNA were measured by real time polymerase
      chain reaction. Nuclear factor kappaB (NF-kappaB) translocation was examined by
      immunofluorescent staining/microscopy. Berberrubine dose-dependently inhibited IL
      8 and MCP-1 protein levels in the media and mRNA expression of the cells
      stimulated with IL-1beta or TNF-alpha. Immunofluorescent staining/microscopy of
      NF-kappaB in the nucleus of unstimulated cells was faint (51+/-14 arbitrary
      units). Fluorescein was dense (215+/-42 or 170+/-24 arbitrary units,
      respectively) 30 min after stimulation with IL-1beta or TNF-alpha and was
      decreased to 62+/-18 or 47+/-16 arbitrary units, respectively, by berberrubine.
      Berberrubine dose-dependently inhibited IL-8 and MCP-1 expression and protein
      secretion induced by IL-1beta or TNF-alpha. Possibly, the effect on chemotactic
      factors may be via suppression of NF-kappaB translocation.

PMID- 16797035
TI  - Bioaccumulation of heavy metals and radionuclides from seawater by encased
      embryos of the spotted dogfish Scyliorhinus canicula.
AB  - Encased embryos of spotted dogfish Scyliorhinus canicula absorbed six radio
      isotopes (241Am, 109Cd, 57Co, 134Cs, 54Mn and 65Zn) directly from seawater during
      short-term experimental exposure, demonstrating the permeability of the egg-case
      to these contaminants. Embryo to water concentration factors (CFs) ranged from
      0.14 for 134Cs to 7.4 for 65Zn. The 65Zn and 57Co CFs increased exponentially
      with embryo length, whereas the CF for 109Cd declined with length. Among
      different components of the encased embryo the egg case was the major repository
      (69-99%) of all six radio-isotopes that were distributed throughout its wall. Egg
      case CFs were as high as 10(3) for 57Co and 65Zn, making it the major source of
      gamma radiation exposure to the embryo and potentially of radio-isotopes for
      continued absorption by the embryo, following the uptake phase of the experiment.
      The patterns of uptake by the egg-case approximated linearity for most isotopes
      and loss rates were isotope-specific; egg-case biokinetics were not greatly
      affected by the viability of the contained embryo. Within the embryo initial data
      on radio isotopic distribution show that the skin is their major site of uptake,
      as previously demonstrated for juveniles.

PMID- 16797036
TI  - A new approach to the determination of cardiac potential distributions:
      application to the analysis of electrode configurations.
AB  - This paper presents a mathematical model and new solution technique for studying
      the electric potential in a slab of cardiac tissue. The model is based on the
      bidomain representation of cardiac tissue and also allows for the effects of
      fibre rotation between the epicardium and the endocardium. A detailed solution
      method, based on Fourier Series and a simple one-dimensional finite difference
      scheme, for the governing equations for electric potential in the tissue and the
      blood, is also presented. This method has the advantage that the potential can be
      calculated only at points where it is required, such as the measuring electrodes.
      The model is then used to study various electrode configurations which have been
      proposed to determine cardiac tissue conductivity parameters. Three electrode
      configurations are analysed in terms of electrode spacing, placement position and
      the effect of including fibre rotation: the usual surface four-electrode
      configuration; a single vertical analogue of this and a two probe configuration,
      which has the current electrodes on one probe and the measuring electrodes on the
      other, a fixed distance away. It is found that including fibre rotation has no
      effect on the potentials measured in the first two cases; however, in the two
      probe case, non-zero fibre rotation causes a significant drop in the voltage
      measured. This leads to the conclusion that it is necessary to include the
      effects of fibre rotation in any model which involves the use of multiple plunge
      electrodes.

PMID- 16797037
TI  - Coexistence in metacommunities: a tree-species model.
AB  - Simple patch-occupancy models of competitive metacommunities have shown that
      coexistence is possible as long as there is a competition-colonization tradeoff
      such as that of superior competitors and dispersers. In this paper, we present a
      model of competition between three species in a dynamic landscape, where patches
      are being created and destroyed at a different rate. In our model, species
      interact according to a linear non-transitive hierarchy, such that species Y(3)
      outcompetes and can invade patches occupied by species Y(2) and this species in
      turn can outcompete and invade patches occupied by the inferior competitor Y(1).
      In this hierarchy, inferior competitors cannot invade patches of species with
      higher competitive ability. Analytical results show that there are regions in the
      parameter space where coexistence can occur, as well as regions where each of the
      species exists in isolation depending on species' life-history traits associated
      with their colonization abilities and extinction proneness as well as with the
      dynamics of habitat patches. In our model, the condition for coexistence depends
      explicitly on patch dynamics, which in turn modulate the limiting similarity for
      species coexistence. Coexistence in metacommunities inhabiting dynamic landscapes
      although possible is harder to attain than in static ones.

PMID- 16797038
TI  - Harvesting induced fluctuations: insights from a threshold management policy.
AB  - In this work, it is shown that in a deterministic context, a threshold policy can
      induce cyclic behavior in an otherwise exploited stable population. These
      dynamics ensue as a result of the combination of the degree of harvesting
      pressure and more protective threshold densities. Virtual equilibrium in variable
      structure systems plays a determinant role in this dynamical outcome.

PMID- 16797039
TI  - A mathematical model for copper homeostasis in Enterococcus hirae.
AB  - Copper is an essential micronutrient for life. It is required by a wide range of
      species, from bacteria to yeast, plants and mammals including humans. To prevent
      the consequences of the excess or deficit of copper, living organisms have
      developed molecular mechanisms that regulate the uptake, efflux, storage and use
      of the metal. However, the limits of homeostatic regulation are not known. Here,
      we take advantage of a simple biological mechanism involved in copper metabolism
      of Enterococcus hirae, to explore how the regulation is achieved by using a set
      of four proteins codified in the cop operon: two P-type ATP-ases copper
      transporters, one copper chaper-one and one Cu-response transcription factor. We
      propose a mathematical model, based on differential equations and the power-law
      formalism (see M.A. Savageau, Chaos 11(1) (2001) 142-159), for the behavior of
      the cop operon and we show that homeostasis is a result of transient dynamics.
      The results derived from the mathematical model allow to measure qualitatively
      the adaptability of the system to its environment. This detailed model has been
      possible thanks to the available experimental biological information provided in
      a sequence of recent works by Solioz and co-workers.

PMID- 16797040
TI  - On the distribution of the proportion of susceptibles.

PMID- 16797041
TI  - Dynamic multipopulation and density dependent evolutionary games related to
      replicator dynamics. A metasimplex concept.
AB  - This paper contains the basic extensions of classical evolutionary games
      (multipopulation and density dependent models). It is shown that classical
      bimatrix approach is inconsistent with other approaches because it does not
      depend on proportion between populations. The main conclusion is that
      interspecific proportion parameter is important and must be considered in
      multipopulation models. The paper provides a synthesis of both extensions (a
      metasimplex concept) which solves the problem intrinsic in the bimatrix model. It
      allows us to model interactions among any number of subpopulations including
      density dependence effects. We prove that all modern approaches to evolutionary
      games are closely related. All evolutionary models (except classical bimatrix
      approaches) can be reduced to a single population general model by a simple
      change of variables. Differences between classic bimatrix evolutionary games and
      a new model which is dependent on interspecific proportion are shown by examples.

PMID- 16797042
TI  - On linear perturbations of the Ricker model.
AB  - A class of linearly perturbed discrete-time single species scramble competition
      models, like the Ricker map, is considered. Perturbations can be of both
      recruitment and harvesting types. Stability (bistability) is considered for
      models, where parameters of the map do not depend on time. For models with
      recruitment, the result is in accordance with Levin and May conjecture [S.A.
      Levin, R.M. May, A note on difference delay equations, Theor. Pop. Biol. 9 (1976)
      178]: the local stability of the positive equilibrium implies its global
      stability. For intrinsic growth rate r-->infinity the way to chaos is broken down
      to get extinction of population for the depletion case and to establish a stable
      two-cycle period for models with immigration. The latter behaviour is also
      studied for models with random discrete constant perturbations of recruitment
      type. Extinction, persistence and existence of periodic solutions are studied for
      the perturbed Ricker model with time-dependent parameters.

PMID- 16797043
TI  - Competition between plasmid-bearing and plasmid-free organisms in a chemostat
      with nutrient recycling and an inhibitor.
AB  - The asymptotic behavior of solutions of a model for competition between plasmid
      bearing and plasmid-free organisms in the chemostat with two distributed delays
      and an external inhibitor is considered. The model presents a refinement of the
      one considered by Lu and Hadeler [Z. Lu, K.P. Hadeler, Model of plasmid-bearing
      plasmid-free competition in the chemostat with nutrient recycling and an
      inhibitor, Math. Biosci. 167 (2000) p. 177]. The delays model the fact that the
      nutrient is partially recycled after the death of the biomass by bacterial
      decomposition. Furthermore, it is assumed that there is inter-specific
      competition between the plasmid-bearing and plasmid-free organisms as well as
      intra-specific competition within each population. Conditions for boundedness of
      solutions and existence of non-negative equilibrium are given. Analysis of the
      extinction of the organisms, including plasmid-bearing and plasmid-free
      organisms, and the uniform persistence of the system are also carried out. By
      constructing appropriate Liapunov-like functionals, some sufficient conditions of
      global attractivity to the extinction equilibria are obtained and the combined
      effects of the delays and the inhibitor are studied.

PMID- 16797044
TI  - Modelling suicide risk in later life.
AB  - Affective disorder is generally regarded as the prominent risk factor for suicide
      in the old age population. Despite the large number of empirical studies
      available in the literature, there is no attempt in modelling the dynamics of an
      individual's level of suicide risk theoretically yet. In particular, a dynamic
      model which can simulate the time evolution of an individual's level of risk for
      suicide and provide quantitative estimates of the probability of suicide risk is
      still lacking. In the present study we apply the contingent claims analysis of
      credit risk modelling in the field of quantitative finance to derive a
      theoretical stochastic model for estimation of the probability of suicide risk in
      later life in terms of a signalling index of affective disorder. Our model is
      based upon the hypothesis that the current state of affective disorder of a
      patient can be represented by a signalling index and exhibits stochastic movement
      and that a threshold of affective disorder, which signifies the occurrence of
      suicide, exists. According to the numerical results, the implications of our
      model are consistent with the clinical findings. Hence, we believe that such a
      dynamic model will be essential to the design of effective suicide prevention
      strategies in the target population of older adults, especially in the primary
      care setting.

PMID- 16797045
TI  - Enthalpy and conformational volume changes of mammalian oxy-hemoglobins
      investigated by pulsed photoacoustic calorimetry.
AB  - Enthalpy and conformational volume changes induced by laser photo-dissociation
      reactions of mammalian oxy-hemoglobin, such as human, bovine, pig, horse and
      rabbit oxy-hemoglobins, are investigated by pulsed photoacoustic calorimetry.
      Generally, the response time of the photoacoustic calorimetry is restricted by
      the width of the laser pulse and the bandwidth of the acoustic detector.
      Considering the time window of the experimental system, the enthalpy and
      conformational volume changes detected should be caused by the tertiary
      relaxation of the heme proteins. In order to calculate the enthalpy and
      conformational volume changes, the quantum yields of the photo-dissociation
      products of oxy-hemoglobins must be measured and taken into account. Finally, the
      enthalpy and conformational volume changes of the oxy-hemoglobins connected with
      the tertiary relaxation are obtained, which show that for all measured mammalian
      oxy-hemoglobins the values of enthalpy changes are in the range of 30.0-46.8
      kcal/mol and volume changes are of 2.3-7.8 ml/mol although the quantum yields for
      the different species may have much bigger differences. A possible explanation of
      the results is presented.

PMID- 16797046
TI  - Nonlinear ultrasonic nature of organic liquid and organic liquid mixture.
AB  - Based on Jacobson's molecular free length theory in liquids and the relationship
      between ultrasonic velocity and the molecular free length in organic liquids,
      this paper deduces the equations for pressure coefficient and temperature
      coefficient of ultrasonic velocity and nonlinear acoustic parameter B/A in both
      of organic liquid and organic liquid binary mixtures. These nonlinear acoustic
      parameters are evaluated against the measured results and data from other
      sources. The equations reveal the connections between the nonlinear acoustic
      parameters and some internal structural of the medium or mixtures e.g. the sizes
      of molecule, several thermodynamic physical parameters and outside status e.g.
      condition of pressure and temperature of the liquid or liquid mixture. With the
      equations the nonlinear acoustic parameter B/A of organic liquid binary mixtures,
      which is impossible to know without the nonlinear acoustic parameter B/A of the
      tow components before, can be calculated based on the structural and physical
      parameters of organic liquid and organic liquid binary mixtures.

PMID- 16797047
TI  - Complete ultrasonic transducer characterization and its use for models and
      measurements.
AB  - Transmitting and receiving properties of ultrasonic piezoelectric crystal
      transducers that directly affect the measured output voltage in an ultrasonic
      measurement system are described. These transducer properties are the
      transducer's electrical impedance and sensitivity, the transducer's radiation
      impedance, and the transducer's effective parameters (effective radius and focal
      length). It is shown that all these properties can be obtained with a series of
      calibration measurements, most of them purely electrical in nature. This series
      of measurements is described, including a newly developed method that makes the
      determination of the transducer sensitivity simpler than with previous methods.
      It is demonstrated that by combining these transducer properties with knowledge
      of the electrical properties of the pulser/receiver and cabling and the
      acoustic/elastic processes present in an ultrasonic measurement system, it is
      possible to accurately simulate the output voltage of the system.

PMID- 16797048
TI  - Characterization of Ta and TaN diffusion barriers beneath Cu layers using
      picosecond ultrasonics.
AB  - In computer chips, aluminum is being replaced with copper in order to produce
      smaller, faster and more efficient electronic devices. The usage of copper allows
      higher current densities and thus higher packaging densities than aluminum.
      However, copper leads to new challenges and problems. It has different mechanical
      properties and a tendency to migrate into the surrounding dielectric and/or
      semiconducting layers. These diffusion processes can be prevented by so called
      diffusion barriers. A diffusion barrier is a very thin layer consisting of
      tantalum and tantalum nitride or titanium and titanium nitride, deposited between
      the copper and the substrate. A pump-probe setup is used to determine the
      mechanical properties of the barrier layers and of the copper layer. This short
      pulse-laser-acoustic method is contact-free and non-destructive. Mechanical waves
      are excited and detected thermoelastically using laser pulses of 70 fs duration.
      Thin film measurements of buried diffusion layers are provided and compared with
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), and
      Rutherford Backscattering Spectroscopy measurements (RBS). Results of a thermo
      elasto-mechanical simulation are presented and a short overview of the simulation
      procedure is given. Current limits of the presented method are discussed and
      future directions of the on-going research project are presented.

PMID- 16797049
TI  - On interference effects in the elastodynamic Green's functions G33(x, omega) of
      Si and GaAs.
AB  - In this paper, we analyze interference effects present in the elastodynamic
      Green's functions G33(x,omega) of the cubic crystals Si and GaAs, which are
      associated with folded portions of the wave surface of the slow transverse (ST)
      acoustic mode. G33(x,omega) represents the three dimensional extension of the
      amplitude distribution imaged in the transmission acoustic microscopy of these
      crystals. The intensity contrast for oscillations of a particular wave vector k
      in the interference pattern is determined essentially by the 3D Fourier transform
      of G33(x,omega)G33*(x,omega). According to the Fourier autocorrelation theorem,
      that transform is equivalent to the autocorrelation function of the corresponding
      distribution G(33)(k,omega) in k-space. We show that due to the linear mapping
      between k-space and the slowness vector s-space, the interference phenomena
      discussed here are related to geometrical features of the slowness surface of the
      ST mode. We present calculations of these effects based on the angular spectrum
      technique.

PMID- 16797050
TI  - Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation
      with frequency during clinical therapy and evidence of compensation for the
      reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V.
AB  - Efavirenz resistance during HIV-1 treatment failure is usually associated with
      the reverse transcriptase mutation K103N. L100I, V108I, or P225H can emerge after
      K103N and increase its level of efavirenz resistance. K103N + L100I is the most
      drug-resistant of the double mutants but is the least common clinically. We
      hypothesized that differences in replication efficiency, or fitness, influence
      the relative frequencies of these secondary efavirenz resistance mutations in
      clinical isolates. We measured fitness of each secondary mutant introduced into
      HIV(NL4-3), alone and in combination with K103N, using growth competition assays
      in H9 cells. In the absence of efavirenz, the fitness of V108I was
      indistinguishable from wild type. K103N, L100I, and P225H were minimally, but
      consistently, less fit than wild type. K103N + L100I had a greater reduction in
      fitness and was less fit than K103N + V108I and K103N + P225H. The fitness defect
      of K103N + L100I relative to K103N was completely compensated for by the addition
      of the nucleoside resistance mutation L74V. In the presence of efavirenz, L100I
      was less fit than K103N, and K103N + L100I was more fit than K103N + V108I. Our
      studies suggest the primary driving force behind the selection of secondary
      efavirenz resistance mutations is the acquisition of higher levels of drug
      resistance, but the specific secondary mutations to emerge are those with the
      least cost in terms of replication efficiency. In addition, nucleoside and NNRTI
      resistance mutations can interact to affect HIV replication efficiency; these
      interactions may influence which mutations emerge during treatment failure. These
      studies have important implications for the design of more durable NNRTI
      nucleoside combination regimens.

PMID- 16797051
TI  - Receptor use by pathogenic arenaviruses.
AB  - The arenavirus family contains several important human pathogens including Lassa
      fever virus (LASV), lymphocytic choriomeningitis virus (LCMV) and the New World
      clade B viruses Junin (JUNV) and Machupo (MACV). Previously, alpha-dystroglycan
      (alpha-DG) was identified as a receptor recognized by LASV and certain strains of
      LCMV. However, other studies have suggested that alpha-DG is probably not used by
      the clade B viruses, and the receptor(s) for these pathogens is currently
      unknown. Using pseudotyped retroviral vectors displaying arenavirus glycoproteins
      (GPs), we are able to explore the role played by the GP in viral entry in the
      absence of other viral proteins. By examining the ability of the vectors to
      transduce DG knockout murine embryonic stem (ES) cells, we have confirmed that
      LASV has an absolute requirement for alpha-DG in these cells. However, the LCMV
      GP can still direct substantial entry into murine ES cells in the absence of
      alpha-DG, even when the GP from the clone 13 variant is used that has previously
      been reported to be highly dependent on alpha-DG for entry. We also found that
      neither LASV or LCMV pseudotyped vectors were able to transduce human or murine
      lymphocytes, presumably due to the glycosylation state of alpha-DG in these
      cells. In contrast, the JUNV and MACV GPs displayed broad tropism on human,
      murine and avian cell types, including lymphocytes, and showed no requirement for
      alpha-DG in murine ES cells. These findings highlight the importance of molecules
      other than alpha-DG for arenavirus entry. An alternate receptor is present on
      murine ES cells that can be used by LCMV but not by LASV, and which is not
      available on human or murine lymphocytes, while a distinct and widely expressed
      receptor(s) is used by the clade B viruses.

PMID- 16797052
TI  - A gamma-herpesvirus deficient in replication establishes chronic infection in
      vivo and is impervious to restriction by adaptive immune cells.
AB  - Chronic gamma-herpesvirus infection is a dynamic process involving latent
      infection, reactivation from latency, and low level persistent replication. The
      gamma-herpesviruses maintain latent infection in restricted subsets of
      hematopoietic cells as a result of an intricate balance between host factors that
      suppress infection and viral factors that facilitate evasion of the immune
      response. Immune effectors limit reactivation and subsequent replication events,
      and the adaptive immune response ultimately restricts infection to a level
      compatible with life-long infection. However, it has not been possible to
      determine whether the immune system constrains chronic infection by directly
      targeting latently infected cells in vivo due to the complex nature of chronic
      infection. To begin to address this issue, we generated a murine gamma
      herpesvirus 68 (gammaHV68) deficient in its ability to replicate or undergo
      reactivation from latency via a mutation in the single-stranded DNA binding
      protein encoded by ORF6. Even in the absence of lytic replication, this virus
      established long-term infection in peritoneal cells of wild-type mice at levels
      identical to that of wild-type gammaHV68, and generated an immune response that
      was sufficient to protect against secondary challenge with wild-type gammaHV68.
      Nevertheless, the number of latently infected cells was not significantly altered
      in mice deficient in T cells or both T cells and B cells, demonstrating that the
      adaptive immune system is incapable of altering infection with a virus lacking
      the capacity for lytic replication and reactivation from latency. Thus, these
      data support the conclusion that latency is immunologically silent.

PMID- 16797053
TI  - Reflection makes sense of rotation of the eyes.
AB  - Our 3-D percept of the world is constructed from the two-dimensional visual
      images on the retina of each eye, but these images and the relationships between
      them are affected by the 3-D rotations of each eye. These 3-D eye rotations are
      constrained to patterns such as Listing's law, or its generalisation 'L2',
      according to the context. Our understanding of the patterns of such three
      dimensional eye rotations, and their effect on the retinal images, has been
      greatly advanced by the development of algebraic methods (Haustein, 1989; Tweed &
      Vilis, 1987; Westheimer, 1957) for calculating the effect of eye rotations. But
      not many would say, with Dirac, that they understand the equations describing the
      3-D geometry in the sense that they have "a way of figuring out the
      characteristic of its solution without actually solving it" (Dirac, according to
      Feynman, Leighton, & Sands, 1964). I show here how the geometry of 3-D rotations
      of the eye and their visual effects can be made easier to understand by use of
      the principle that a rotation through angle alpha can be achieved by a pair of
      reflections in planes with an angular separation alpha/2, and a common line that
      is the rotation axis (Tweed, 1997b; Tweed, Cadera, & Vilis, 1990). Mathematically
      (see Appendix A), the method is equivalent to decomposing the unit quaternions so
      successfully used to study three-dimensional eye rotations (Tweed & Vilis, 1987;
      Westheimer, 1957) into pairs of pure quaternions (ones whose scalar part is zero)
      which represent the reflections (Coxeter, 1946).

PMID- 16797054
TI  - Binding of Pb(II) in the system humic acid/goethite at acidic pH.
AB  - The study of Pb(II) binding to the system humic acid/goethite in acidic medium is
      reported in the present paper. From a macroscopic point of view, we have
      constructed the experimental sorption isotherms (using atomic absorption
      spectroscopy) and compared them with the prediction of the additivity rule. It is
      found that this system presents positive deviations, that is, the amount sorbed
      is about an order of magnitude higher than predicted. Apart from this,
      microscopic and structural aspects have also been studied using in situ and ex
      situ infrared spectroscopy. These results suggest that the presence of Pb(II)
      increases the amount of humic acid bound to the oxide. It is proposed that proton
      displacement due to the interaction between humic substances and the oxide, along
      with the formation of ternary complexes with the Pb(II) cation bridging the oxide
      and the humic substances (Type A complexes), cause the deviation from additivity.

PMID- 16797056
TI  - Examining affinities of the Taung child by developmental simulation.
AB  - As a well-preserved juvenile and the type specimen of Australopithecus africanus,
      the Taung child figures prominently in taxonomic, ontogenetic, and phylogenetic
      analyses of fossil hominins. Despite general agreement about allocation of
      Sterkfontein and Makapansgat fossils to this species, limited morphological
      comparisons have been possible between these adult specimens and the juvenile
      Taung. Here, we used developmental simulation to estimate the adult form of the
      Taung child, and directly compare its morphology to that of other fossil
      hominins. Specimens were represented by 50 three-dimensional landmarks
      superimposed by generalized Procrustes analysis. The simulation process applied
      developmental trajectories from extant hominine species to the Taung fossil in
      order to generate its adult form. Despite differences found in the developmental
      patterns of these modern species, simulations tested on extant juveniles
      transforming them into "adults" using trajectories from other species-revealed
      that these differences have negligible impact on adult morphology. This indicates
      that morphology already present by occlusion of the first permanent molar is the
      primary determinant of adult form, thereby supporting use of extant trajectories
      to estimate the morphology of an extinct species. The simulated Taung adult was
      then compared to other adult fossils. As these comparisons required assumptions
      about the pattern and magnitude of developmental change, additional analyses were
      performed to evaluate these two parameters separately. Results of all analyses
      overwhelmingly rejected the possibility that the Taung child was a juvenile
      robust australopith, but were consistent with the hypothesis that the Taung and
      Sterkfontein fossils are conspecific. Between Sts 5 and Sts 71, the latter is
      more likely to resemble the adult form of the Taung child.

PMID- 16797055
TI  - How long does it take to become a proficient hunter? Implications for the
      evolution of extended development and long life span.
AB  - Human hunting is arguably one of the most difficult activities common to foraging
      peoples now and in the past. Children and teenagers have usually been described
      as incompetent hunters in ethnographies of hunter-gatherers. This paper explores
      the extent to which adult-level competence is limited more by the constraints of
      physical capital, or body size, and brain-based capital, or skills and learning.
      The grandmother hypothesis requires that production is an increasing function of
      size alone, while the embodied capital model stipulates that production is a
      function of both size and delayed learning. Tests based on observational,
      interview, and experimental data collected among Tsimane Amerindians of the
      Bolivian Amazon suggest that size alone cannot explain the long delay until peak
      hunting productivity. Indirect encounters (e.g., smells, sounds, tracks, and
      scat) and shooting of stationary targets are two components of hunting ability
      limited primarily by physical size alone, but the more difficult components of
      hunting--direct encounters with important prey items and successful capture-
      require substantial skill. Those skills can take an additional ten to twenty
      years to develop after achieving adult body size.

PMID- 16797057
TI  - Delayed effects of low level acute irradiation and chronic environmental
      radioactive contamination on DNA lymphocytes of people living in Dolon, a
      settlement located in the vicinity of the Semipalatinsk nuclear test site
      (Kazakhstan).
AB  - During 42 years several hundred nuclear tests were performed by the former USSR
      at the Semipalatinsk Test Site (STS, Kazakhstan), of which more than 100 were
      done in the atmosphere. We report here the late genetic damage of external
      exposure to radiation and environmental radioactive contamination in people
      living in Dolon, a small settlement situated in the vicinity of the STS. The
      comet assay was applied on DNA lymphocytes of 20 exposed women and 32 non-exposed
      women living at 500 km from the STS. We observed a statistically significant
      difference between the exposed and control groups for mean tail moment (MTM) and
      DNA% in the tail. The mean values of all comet assay parameters (MTM, DNA% in the
      tail and score) were higher in the group of women born before 1949 as compared to
      those born after 1950, which could reflect an effect of external irradiation in
      1949 due to the most contaminating explosion. These results suggest that people
      exposed 50 years ago to relatively small doses of external irradiation and/or
      still living in an environment contaminated by small amounts of long life
      radionuclides, still present DNA damage which is in agreement with other
      cytogenetical studies performed at the same site, on the same population.

PMID- 16797058
TI  - Quantification of platelet composition in experimental venous thrombosis by real
      time polymerase chain reaction.
AB  - INTRODUCTION: Platelets play a key role in thrombus formation. Determination of
      the platelet component in a thrombus provides pathophysiological insights to the
      thrombotic event and aids in selecting an appropriate therapeutic intervention.
      In this study a sensitive and reliable method to characterize the cellular
      components of experimental thrombi was developed using real-time polymerase chain
      reaction (PCR). METHODS AND RESULTS: Vena cava thrombosis was induced by either
      oxidative injury to topical FeCl(2) (FeCl(2)-VT) or stenosis-limited blood flow
      and a hypotonic pressure stress (stasis-VT) in rats. High levels of platelets
      were identified in the thrombus containing vessels by real-time PCR analysis of
      target gene amplification using the 2(-DeltaDeltaCT) values by normalizing the
      data with gene expression in naive vessels and with a housekeeping gene,
      ribosomal protein L32. By this analysis, the levels of PF-4 (as a platelet
      marker) mRNA were significantly higher in FeCl(2)-VT (2(-DeltaDeltaCT)=7.8) than
      in stasis-VT (2(-DeltaDeltaCT)=4.2, p<0.05). Enhanced platelet enrichment in
      FeCl(2)-VT was also confirmed qualitatively by scanning electronic microscopic
      analysis. In addition, real-time PCR using a panel of genes representing vascular
      injury, inflammation and thrombosis showed marked induction (2(-DeltaDeltaCT)>5)
      in MCP-1, IL-1beta, iNOS and P-selectin mRNA expression in both models.
      CONCLUSIONS: These data demonstrate the utility of real-time PCR to quantitate
      platelets and other cell components in vascular thrombosis, which may facilitate
      the characterization and thus therapeutic intervention of a particular thrombotic
      event in both preclinical animal models and clinical conditions.

PMID- 16797059
TI  - Novel function of human ADAM15 disintegrin-like domain and its derivatives in
      platelet aggregation.
AB  - INTRODUCTION: A Disintegrin and Metalloproteinase (ADAM) proteins are a family of
      multifunctional proteins containing disintegrin and metalloproteinase domains
      that perform both adhesive and proteolytic functions in cell-cell and cell-matrix
      interactions. ADAM15 is unique among these proteins in having an Arg-Gly-Asp
      (RGD) motif in its disintegrin-like domain. This motif is known to interact with
      the integrin alphaIIbbeta3 on platelets. MATERIALS AND METHODS: We cloned and
      expressed the human ADAM15 disintegrin-like domain and its derivatives in Pichia
      pastoris, and purified them by chromatographic fractionation. We then
      characterized the integrin binding specificities and their antiplatelet
      activities of the proteins. Antiplatelet function was assessed by inhibition of
      platelet adhesion and aggregation. RESULTS: The yeast-expressed ADAM15
      disintegrin-like domains were able to inhibit the binding of alphaIIbbeta3 as
      well as alphavbeta3 to its biological ligands in a dose-dependent manner.
      Remarkably, mutation of the three residues proximal to the RGD tripeptide
      sequence, RPTRGD sequence to NWKRGD, increased its affinity for alphaIIbbeta3.
      The NWK mutant had a much greater inhibitory action on human platelet aggregation
      than the original ADAM15 disintegrin-like domain. CONCLUSIONS: The structural
      context of the RGD tripeptide sequence in the disintegrin domain determines the
      specificity and affinity of the protein for its binding partners. The human
      ADAM15 disintegrin-like domain may provide useful information for developing an
      antithrombotic agent.

PMID- 16797060
TI  - Evaluation of the incidence of carboplatin hypersensitivity reactions in cancer
      patients.
AB  - OBJECTIVES: Although the reported incidence of carboplatin hypersensitivity is
      low, its occurrence is important to characterize because of potential fatal
      complications. The purpose of this study was to determine the current incidence
      of carboplatin hypersensitivity in the ovarian cancer patients compared to other
      oncology patients and identify potential risk factors that may contribute to
      development of carboplatin hypersensitivity reactions. METHODS: This was a
      retrospective chart review analyzing all hospital records at an academic tertiary
      oncology center between July 2002 and September 2003. Data collected included
      patient demographics, past medical histories, and detailed carboplatin
      administration information. Patients that had received carboplatin were
      identified from pharmacy dispensing records. Positive carboplatin
      hypersensitivity reactions were identified from the documentation provided in the
      patient medical record. RESULTS: The incidence of carboplatin hypersensitivity
      for all cancer patients compared to ovarian cancer patients receiving carboplatin
      at our institution was 2.6% and 7.9%, respectively. Statistically significant
      risk factors (P < 0.05) included prior carboplatin exposure and history of drug
      allergies. There was also a trend to suggest premedication with histamine1 (H1)
      and histamine(2) (H2) blocker decreases the risk of developing carboplatin
      hypersensitivity reactions. CONCLUSION: This study confirmed a similar incidence
      of carboplatin hypersensitivity reactions to previous reports. However, we found
      that the higher incidence associated with ovarian cancer patients can be
      attributed to the prolonged carboplatin exposure or history of drug allergies.
      This is the first study to observe that the administration of H1 and H2
      antagonists is associated with a decrease risk of carboplatin hypersensitivity
      reaction.

PMID- 16797061
TI  - Zingiber officinale exhibits behavioral radioprotection against radiation-induced
      CTA in a gender-specific manner.
AB  - At the organismic level, exposure to radiation can produce taste aversion (CTA)
      learning and emesis, which have been proposed as behavioral endpoints that are
      mediated by harmful effects of radiations on peripheral systems, primarily the
      gastrointestinal system. Thus, the aim of the present investigation was to study
      the gastroprotective action of hydroalcoholic extract of zingiber rhizome
      (Zingiber officinale Rosc.) against radiation-induced conditioned taste aversion
      (CTA) in both male and female species of animals, for testing its potential as a
      behavioral radioprotector. Administration of zingiber extract 1 h before 2-Gy
      gamma-radiation was significantly effective in blocking the saccharin avoidance
      response, with 200 and 250 mg/kg b.wt. i.p., being the most effective doses for
      male and female rats, respectively. A comparison of the efficacy of zingiber
      extract with two antiemetic drugs, ondansteron and dexamethasone, revealed that
      the extract rendered comparable protection against radiation-induced CTA. Our
      experiments also confirmed the existence of sex dichotomy (i.e., the sex of
      animal greatly influenced response towards radiation exposure) in relation to
      behavioral responses (CTA) or differential metabolism. The observed gender
      variations were hypothesized to be a result of hormonal fluctuations and
      differences in pharmacological parameters in male and female rats. To correlate
      the mechanism of action, the free-radical-scavenging potential of zingiber
      extract to scavenge hydroxyl ion and nitric oxide was also tested, in cell-free
      system and a concentration of 1000 microg/ml, was found to be the most potent,
      which has been proposed as one the many activities assisting in its overall
      ability to modulate radiation-induced taste aversion. The results demonstrate
      that Z. officinale possesses antioxidant, radioprotective and neuromodulatory
      properties that can be effectively utilized for behavioral radioprotection and
      for efficiently mitigating radiation-induced CTA in both males and females
      species.

PMID- 16797062
TI  - Hypernociception elicited by tibio-tarsal joint flexion in mice: a novel
      experimental arthritis model for pharmacological screening.
AB  - Mice have been used as animal model to study mechanisms underlying inflammatory
      and immune diseases. The present study describes a model of joint inflammation
      induced hypernociception to discriminate pharmacological tests in mice. A
      polypropylene tip probe with a large area (4.15 mm2) applied on the plantar
      surface of the hind paw was used to produce a dorsal flexion of tibio-tarsal
      joint. Experiments were performed to demonstrate that the probe application did
      not provoke cutaneous nociception. The decrease in the withdrawal threshold of
      inflamed joint was used as nociceptive parameter. Administration of zymosan in
      the tibio-tarsal joint induced a dose and time-dependent hypernociception
      elicited by articular dorsal flexion movement. Maximal joint hypernociception was
      detected between 7 and 24 h after zymosan injection, and matched maximal
      inflammation score as determined by histopathology and neutrophil migration
      assay. In agreement with the inflammatory hypernociceptive paradigm, flexion
      elicited hypernociception induced by zymosan was dose-dependently inhibited by
      morphine (2-8 mg/kg) and by an effective dose of indomethacin (5 mg/kg). The
      present study demonstrated that the tibio-tarsal flexion reflex is a behavioral
      nociceptive model that allows a quantitative evaluation of inflammatory joint
      hypernociception in mice and its pharmacological modulation.

PMID- 16797063
TI  - Behavioral and genoprotective effects of Vaccinium berries intake in mice.
AB  - Studies have shown that supplementation with berries rich in anthocyanins are
      effective in reducing oxidative stress associated with aging, and are beneficial
      in reversing age-related neuronal and behavioral changes. However, there are few
      reports on other biological activities of these polyphenols, such as
      genoprotective effects. The present experiments were performed to study the
      possible effects of 30-day administration of a lyophilized extract of Vaccinium
      ashei berries on cognitive performance using step-down inhibitory avoidance, open
      field habituation and elevated plus-maze tasks, as well as on DNA damage in the
      hippocampus and cerebral cortex. The present study showed that the extract
      significantly enhanced long-term memory in the inhibitory avoidance task, induced
      an increase in the number of crossings during open-field habituation and had an
      anxiolytic effect in the elevated plus-maze task. Moreover, the extract reduced
      oxidative DNA damage in brain tissue in vitro. These results suggest that
      supplementation with V. ashei berries to mice improves performance on memory
      tasks and has a protective effect on DNA damage, possibly due to the antioxidant
      activity of polyphenols, including anthocyanins.

PMID- 16797064
TI  - The effect of season on serum testosterone concentrations in dogs.
AB  - Photoperiod and environmental temperature are two important factors that may
      influence the reproductive cycle of various species. The objective of this study
      was to investigate seasonal influences on serum testosterone concentrations in
      dogs in a tropical zone, where the variation in day length between winter and
      summer solstice was approximately 2.5 h. Blood samples were collected every 15
      days from seven adult dogs over a 14-month interval and serum testosterone
      concentrations were determined by radioimmunoassay. The year was divided into
      four seasons and mean testosterone concentrations for each season were related to
      the mean environmental temperature and rainfall during that season. Mean
      testosterone concentrations were 1.81 ng/mL (winter 2002), 1.93 ng/mL (spring
      2002), 1.31 ng/mL (summer 2003), 2.02 ng/mL (autumn 2003) and 1.93 ng/mL (winter
      2003). The temperature ranged from 10.2 to 32.8 degrees C and the rainfall from
      33 to 476 mm. Serum testosterone concentrations were lower in summer 2003 than in
      both spring 2002 (P = 0.05) and autumn 2003 (P = 0.016). In a tropical zone, a
      combination of high temperature and substantial rainfall may have reduced serum
      testosterone concentrations in dogs.

PMID- 16797065
TI  - Breed differences in competitive indices of Holstein and Jersey bulls and their
      association with sperm DNA fragmentation index and plasma membrane integrity.
AB  - The objective was to evaluate the relationship of a competitive index (CI)
      determined by heterospermic performance and post-thaw semen quality of the same
      stored ejaculates. Semen from multiple ejaculates collected in succession from
      each bull (four Holstein and four Jersey) was pooled. Heterospermic doses
      (20x10(6)/straw) were made to obtain all possible Holstein-Jersey combinations
      (16 two-bull combinations) and contained 20x10(6) sperm/mL/bull. Cows at two
      University dairy farms were inseminated on observed or synchronized estrus. The
      sire of calves (N=460) were determined and a CI was determined for each bull
      (based on the number of calves sired). Prior to preparation of the heterospermic
      doses, a sub-sample of semen from each bull was taken, processed, frozen, and
      stored concurrently with heterospermic samples. Post-thaw semen samples
      (homospermic) from each bull were assessed for: sperm morphology, acrosome
      integrity, sperm motility parameters assessed by computer assisted sperm analysis
      (CASA), flow cytometry analysis of DNA Fragmentation Index (DFI), and Plasma
      Membrane Integrity (PMI). Heterospermic performance of Holstein bulls was
      superior to that of Jersey bulls. The DFI was negatively correlated to CI (r=
      0.87; P<0.001), whereas the PMI (r=0.87; P<0.001) and total progressive motility
      (r=0.74; P<0.05) assessed by CASA were positively correlated to CI. In
      multivariate regression models, the DFI and PMI accounted for 87% variance in
      competitive index. In conclusion, bulls with less DFI and higher PMI had higher
      probabilities of siring calves.

PMID- 16797066
TI  - Modulation of biorecognition of glucoamylases with Concanavalin A by
      glycosylation via recombinant expression.
AB  - Various types of glucoamylases were prepared to modulate their biospecific
      interaction with Concanavalin A. Glucoamylase Glm was isolated from the native
      yeast strain Saccharomycopsis fibuligera IFO 0111. Two glycosylated recombinant
      glucoamylases Glu's of S. fibuligera HUT 7212 were expressed and isolated from
      the strains Saccharomyces cerevisiae and one, nonglycosylated, from Escherichia
      coli. The biospecific affinity of those preparations to Concanavalin A was
      investigated and compared with the commercially available fungal glucoamylase GA
      from Aspergillus niger. All glycosylated enzymes showed affinity to Concanavalin
      A characterized by their precipitation courses and by the equilibration
      dissociation constants within the range from 1.43 to 4.17 x 10(-6) M (determined
      by SPR method). The results suggested some differences in the interaction of Con
      A with the individual glucoamylases. The highest affinity to Con A showed GA. The
      recombinant glucoamylase Glu with the higher content of the saccharides was
      comprised by two binding sites with the different affinity. The glucoamylases
      with the lowest affinity (Glm and Glu with a lower content of saccharides) also
      demonstrated a nonspecific interaction with Con A in the precipitation
      experiments. The minimal differences between the individual glucoamylases were
      determined by the inhibition experiments with methyl-alpha-d-mannopyranoside.

PMID- 16797067
TI  - Collagen mimetic peptide-conjugated photopolymerizable PEG hydrogel.
AB  - Collagen mimetic peptide (CMP) with a specific amino acid sequence, -(Pro-Hyp
      Gly)(x)-, forms a triple helix conformation that resembles the native protein
      structure of natural collagens. CMP previously has been shown to associate with
      type I collagen molecules and fibers via a strand invasion process. We
      hypothesized that when poly(ethylene glycol) (PEG) hydrogel, a non-adhesive
      tissue engineering scaffold, is conjugated with CMP, it may retain cell-secreted
      collagens and also form physical crosslinks that can be manipulated by cells. A
      photopolymerizable CMP derivative was synthesized and copolymerized with
      poly(ethylene oxide) diacrylate to create a novel PEG hydrogel. In a model
      retention experiment, diffusional loss of type I collagen that was added to the
      hydrogel was limited. Chondrocytes were encapsulated in the hydrogel to examine
      its use as a tissue engineering scaffold. After 2 weeks, the biochemical analysis
      of the CMP-conjugated PEG gel revealed an 87% increase in glycosaminoglycan
      content and a 103% increase in collagen content compared to that of control PEG
      hydrogels. The histology and immunohistochemistry analyses also showed increased
      staining of extracellular matrix. These results indicate that the CMP enhances
      the tissue production of cells encapsulated in the PEG hydrogel by providing cell
      manipulated crosslinks and collagen binding sites that simulate natural
      extracellular matrix.

PMID- 16797068
TI  - T-type calcium channels in differentiation and proliferation.
AB  - Low-voltage activated, T-type calcium channels (T-channels) are expressed in many
      developing tissues and may be important in regulating important cellular
      phenotype transitions leading to cell proliferation, differentiation, growth and
      death. The purpose of this review is to relate and delineate the current data on
      the involvement of T-channels in differentiation and proliferation. Owing to the
      recent cloning of the CaV3.1, CaV3.2 and CaV3.3 subunits coding for T-channels,
      classical electrophysiological and pharmacological approaches are now being
      supported by molecular investigations. As T-channels are expressed in early
      development as well as re-expressed in several disease-states, our goal is to
      provide a comprehensive scheme of the current hypothesis connecting the activity
      of T-channels to cell differentiation and proliferation, as well as the potential
      physiological and pathophysiological implications.

PMID- 16797069
TI  - T-type calcium channels: the never ending story.
AB  - T-type, or low-voltage-activated (LVA), tiny and transient Ca2+ currents pare
      more and more recognised as universal players in a plethora of cell functions and
      are also more and more connected to several diseases. This short introduction
      reviews the discovery of T-type Ca2+ channels, describes its basic properties and
      sketches its cloning and physiological impact. Finally, an overview is given how
      research on T-type Ca2+ channels has developed in the last years and in which
      topics it is branching out, a process, which is still ongoing.

PMID- 16797070
TI  - Identification of PML-RARA rearrangement by RT-PCR and sequencing in an acute
      promyelocytic leukemia without t(15;17) on G-banding and FISH.
AB  - Acute promyelocytic leukemia (APL) is characterized by a reciprocal
      translocation, t(15;17) (q22;q12), resulting in fusion of the genes promyelocytic
      leukemia (PML) and retinoic acid receptor alpha (RARA). With conventional
      cytogenetic methods, these translocations are detected in about 70-90% of
      patients, with most of the negative results due to technical problems or cryptic
      variants. Those masked PML-RARA fusions can be identified by molecular analyses
      such as reverse transcriptase-polymerase chain reaction (PCR) and fluorescence in
      situ hybridization (FISH). We have studied a patient showing morphological,
      cytochemical, and immunophenotypic features of hypergranular APL with trisomy 8
      as a sole anomaly. t(15;17) was not evident on FISH tests, while RT-PCR and cDNA
      sequencing revealed the presence of PML-RARA transcripts.

PMID- 16797071
TI  - Assessment of ecotoxicological risks related to depositing dredged materials from
      canals in northern France on soil.
AB  - The implementation of an ecological risk assessment framework is presented for
      dredged material deposits on soil close to a canal and groundwater, and tested
      with sediment samples from canals in northern France. This framework includes two
      steps: a simplified risk assessment based on contaminant concentrations and a
      detailed risk assessment based on toxicity bioassays and column leaching tests.
      The tested framework includes three related assumptions: (a) effects on plants
      (Lolium perenne L.), (b) effects on aquatic organisms (Escherichia coli,
      Pseudokirchneriella subcapitata, Ceriodaphnia dubia, and Xenopus laevis) and (c)
      effects on groundwater contamination. Several exposure conditions were tested
      using standardised bioassays. According to the specific dredged material tested,
      the three assumptions were more or less discriminatory, soil and groundwater
      pollution being the most sensitive. Several aspects of the assessment procedure
      must now be improved, in particular assessment endpoint design for risks to
      ecosystems (e.g., integration of pollutant bioaccumulation), bioassay protocols
      and column leaching test design.

PMID- 16797072
TI  - Ecosystem carbon budgeting and soil carbon sequestration in reclaimed mine soil.
AB  - Global warming risks from emissions of green house gases (GHGs) by anthropogenic
      activities, and possible mitigation strategies of terrestrial carbon (C)
      sequestration have increased the need for the identification of ecosystems with
      high C sink capacity. Depleted soil organic C (SOC) pools of reclaimed mine soil
      (RMS) ecosystems can be restored through conversion to an appropriate land use
      and adoption of recommended management practices (RMPs). The objectives of this
      paper are to (1) synthesize available information on carbon dioxide (CO2)
      emissions from coal mining and combustion activities, (2) understand mechanisms
      of SOC sequestration and its protection, (3) identify factors affecting C
      sequestration potential in RMSs, (4) review available methods for the estimation
      of ecosystem C budget (ECB), and (5) identify knowledge gaps to enhance C sink
      capacity of RMS ecosystems and prioritize research issues. The drastic
      perturbations of soil by mining activities can accentuate CO2 emission through
      mineralization, erosion, leaching, changes in soil moisture and temperature
      regimes, and reduction in biomass returned to the soil. The reclamation of
      drastically disturbed soils leads to improvement in soil quality and development
      of soil pedogenic processes accruing the benefit of SOC sequestration and
      additional income from trading SOC credits. The SOC sequestration potential in
      RMS depends on amount of biomass production and return to soil, and mechanisms of
      C protection. The rate of SOC sequestration ranges from 0.1 to 3.1 Mg ha(-1) yr(
      1) and 0.7 to 4 Mg ha(-1) yr(-1) in grass and forest RMS ecosystem, respectively.
      Proper land restoration alone could off-set 16 Tg CO2 in the U.S. annually.
      However, the factors affecting C sequestration and protection in RMS leading to
      increase in microbial activity, nutrient availability, soil aggregation, C build
      up, and soil profile development must be better understood in order to formulate
      guidelines for development of an holistic approach to sustainable management of
      these ecosystems. The ECBs of RMS ecosystems are not well understood. An
      ecosystem method of evaluating ECB of RMS ecosystems is proposed.

PMID- 16797073
TI  - Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons
      correlates with platinum-DNA binding.
AB  - Cisplatin has been in use for 40 years, primarily for treatment of ovarian and
      testicular cancer. Oxaliplatin is the only effective treatment for metastatic
      colorectal cancer. Neurotoxicity occurs in up to 30% of patients and is dose
      limiting for both drugs. The neuropathy is characterized by selective sensory
      loss in the extremities. Cisplatin treatment is associated with high levels of Pt
      DNA binding and apoptosis of dorsal root ganglion (DRG) neurons. In this study,
      we directly compared the effects of oxaliplatin on DRG in vitro. Compared with
      cisplatin, oxaliplatin formed fewer Pt-DNA adducts following 6, 12, 24, and 48h
      (0.007ng Pt/mug DNA, 0.012ng/microg, 0.011ng/microg, 0.011ng/microg versus
      0.014ng/microg, 0.022ng/microg, 0.041ng/microg, 0.030ng/microg), respectively.
      These findings closely correlated with data on cell survival where equimolar
      concentrations of oxaliplatin induced less cell death than cisplatin. Oxaliplatin
      induced DRG death was associated with the morphological characteristics of
      apoptosis defined by 4'-6-diamidino-2-phenylindole and annexin/propidium iodide
      staining. Death was completely inhibited by the caspase inhibitor z-VAD-fmk. Our
      results demonstrate that both compounds cause apoptosis of DRG neurons but
      compared to cisplatin, oxaliplatin forms fewer Pt-DNA adducts and is less
      neurotoxic to DRG neurons in vitro.

PMID- 16797074
TI  - Lipid oxidative damage and distribution of inorganic arsenic and its metabolites
      in the rat nervous system after arsenite exposure: influence of alpha tocopherol
      supplementation.
AB  - Inorganic arsenic (iAs) exposure causes peripheral neuropathy. Oxidative effects
      caused by iAs exposure in peripheral nerves have been incompletely characterized.
      This study analyzed arsenic and lipid oxidative damage in the brain, spinal cord,
      and sciatic and sensory sural nerves following arsenite exposure. This study also
      explored whether alpha tocopherol (alpha-TOC) administration mitigates arsenite
      induced oxidative damage. Thiobarbituric acid-reactive substance (TBARS) levels
      and distributions of iAs and its metabolites were evaluated in male Wistar rats
      following 30d of sodium arsenite exposure (10mg/kg bodyweight (bw)/d, by gavage).
      A second group also received alpha-TOC (125mg/kg bw/d, by gavage) during the
      final 20d of arsenite administration. Arsenite exposure caused increased TBARS
      levels within each region of the nervous system; oxidative stress was most
      pronounced in the sural and sciatic nerves. In addition there was a positive
      quadratic relationship between TBARS levels and the concentration of arsenicals
      found in the nervous system (r(2)=0.878, p<0.001). Dimethylarsenic was the
      predominant metabolite of iAs found. Animals alpha-TOC-treated had a 1.7-5.2-fold
      reduction in TBARS levels when compared with rats that received iAs alone. These
      results suggest that oxidative damage may be the main mechanism of toxicity
      induced by exposure of the peripheral nervous system to arsenite and that such
      damage could be attenuated by alpha-TOC-supplementation.

PMID- 16797076
TI  - Laryngeal leishmaniasis in Malta.
AB  - The localization of Leishmania spp. in the larynx is rare especially when not
      associated with immunosuppression or with visceral or cutaneous leishmaniasis. We
      present a case of isolated laryngeal leishmaniasis, the first of its kind
      documented in Malta and infrequently reported from the Mediterranean basin.

PMID- 16797077
TI  - Irregularity in neocortical spike trains: influence of measurement factors and
      another method of estimation.
AB  - Irregularity in the interspike interval is a common phenomenon especially in the
      neocortex. A measure of this random variation in the spacing between neuronal
      spikes is usually obtained with the coefficient of variation CV (standard
      deviation/mean interspike interval). In excitable cells, the standard deviation
      in the interspike interval can be large and the mean firing rate often
      fluctuates. As a result, there can be substantial variability in the value of the
      CV computed for the same spike train using only slightly different samples as we
      show. Moreover, these CV values can be comparatively meaningless unless certain
      conditions are met. In doing so some researchers have selectively sampled data
      over a stable mean while others have used a wide range of trial times or subsets
      thereof (capture window) to compute the CV. This has made interpretation of the
      raw CV cumbersome. We demonstrate that the CV has a triple sensitivity, namely,
      for the size of the capture window, the spike count and the refractory period. We
      assuage these difficulties by introducing a modified term, the coefficient of
      variation proportion of maximum (CVpm) that offers transportability across
      different experimental conditions by compensating for the triplet.

PMID- 16797078
TI  - Long-term outcome of antidepressant-refractory depression: the relevance of
      unrecognized bipolarity.
AB  - BACKGROUND: The long-term outcome of antidepressant-refractory depression is not
      well known. Therefore, the present study investigated the long-term outcome of 26
      antidepressant-refractory patients with depression, whom we had studied and
      treated in 1995. METHODS: Before being classified as nonresponse, these patients
      had been treated adequately with at least two tricyclic or heterocyclic
      antidepressants (a minimum of the equivalent of 150 mg of imipramine for 4
      weeks). In 1995, 21 of 26 patients were diagnosed with unipolar depression, while
      5 were diagnosed with bipolar depression. Mean follow-up was 5.7 years (range: 1
      7 years) and changes in diagnosis, remission and treatment efficacy were
      evaluated. RESULTS: Following the long-term follow-up, 13 patients achieved full
      remission and demonstrated high social functioning (mean GAF score, 91). A
      further four depressed patients experienced full remission; however, subsequent
      recurrence was observed. In total, 17 of 26 patients experienced remission at
      least once during the long-term follow-up period despite the chronic depressive
      episodes observed at study entry. Adjuvant treatment with lithium, dopamine
      receptor agonists or thyroid hormone was effective for promoting full remission.
      Among the 21 patients initially diagnosed with unipolar depression in 1995,
      diagnoses were changed to bipolar disorder in 5 cases. LIMITATIONS: This
      naturalistic study had a relatively small sample size and treatment was not
      controlled. CONCLUSIONS: Long-term follow-up revealed that a substantial
      proportion of antidepressant-refractory depression is comprised of bipolar
      disorders. In addition, augmentation therapies are effective for promoting full
      remission among chronically depressed patients without a risk of serious side
      effects.

PMID- 16797079
TI  - Changes in the seasonality of suicides over time in Slovenia, 1971 to 2002.
AB  - BACKGROUND: Recent studies have reported changes in the time patterns of suicide,
      with reduced seasonality in some European and Asian countries. Anyway conflicting
      data were reported on the fading of suicide seasonality, and in some countries a
      rising trend was reported. METHODS: Harmonic spectral analysis was used to
      analyze all suicides in Slovenia in the years 1971 to 2002 (14,325 among males;
      4350 among females). Analyses of overall changes are based on data aggregated by
      intervals of 8 years. RESULTS: In both sexes, seasonal variance accounts for a
      statistically significant proportion of total variance (36.0% among males; 13.3%
      among females). Anyway in both sexes the season-attributable variance in the
      latest interval is considerably lower than in the preceding periods. LIMITATIONS:
      Data could not be analyzed according to age or to mental disorder diagnosis,
      since this information was not available. CONCLUSION: The seasonal effect on
      mortality by suicide is sensitive to change, but its causes seem not to be sex
      dependant.

PMID- 16797080
TI  - Antidepressant withdrawal symptoms-telephone calls to a national medication
      helpline.
AB  - AIMS AND METHOD: Withdrawal symptoms are associated with cessation of all
      antidepressants but particularly paroxetine and venlafaxine. We aimed to examine
      rates of withdrawal symptoms reported to a national medication helpline over
      seven and a half year period. All calls reporting symptoms of antidepressant
      withdrawal were noted from a retrospective examination of contemporaneous
      handwritten records. RESULTS: Between October 1997 and March 2005, the national
      medication helpline received 22,422 calls of which 1753 (7.8%) concerned
      antidepressant discontinuation symptoms. Of these, 690 calls (39.36%) related to
      paroxetine and 252 (14.38%) to venlafaxine. Calls regarding paroxetine increased
      ten-fold in the month following a BBC 'Panorama' programme centring on problems
      associated with its use. Comparing number of calls with the number of
      prescriptions written over the same period revealed that MAOIs have the highest
      rate of reported reactions. CLINICAL IMPLICATIONS: Withdrawal symptoms were
      reported with nearly all antidepressants but most commonly with paroxetine and
      venlafaxine. Television programmes reporting adverse consequences of drug therapy
      can greatly increase reporting of discontinuation reactions. The highest rate of
      reporting adverse discontinuation symptoms was for MAOIs.

PMID- 16797081
TI  - Association study of BDNF and CNTF polymorphism to depression in non-demented
      subjects of the "VITA" study.
AB  - BACKGROUND: Neurotrophic factors are known to play an important role in the
      survival and differentiation of many types of neurons during development. Both
      brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF)
      may act cooperatively in modulating the development and functioning of synapses.
      Both these neurotrophic factors were intensely investigated with regard to
      depression without conclusive results. METHODS: We have investigated the possible
      use of both CNTF null-mutation and BDNF polymorphism C270T as biomarkers for
      depression in the Vienna Transdanube Aging (VITA) study. The VITA is a
      prospective community-based cohort study of all 75 years old inhabitants of a
      geographical region of Vienna. RESULTS: We found no association between CNTF null
      mutation and BDNF C270T polymorphism to any depressive symptoms after exclusion
      of demented subjects. CONCLUSION: These results call in question the hypothesis
      that either BDNF or CNTF can be used as molecular markers for depression or late
      onset depression in the elderly.

PMID- 16797082
TI  - Deficit in theory of mind is a risk for relapse of major depression.
AB  - BACKGROUND: Recently, we reported that patients with depression have theory of
      mind (ToM) deficit during remission from acute episodes. ToM deficit means
      difficulty in social adjustment and thus may indicate a poorer prognosis.
      METHODS: We evaluated ToM ability of 50 patients during remission from major
      depressive episodes. The patients were followed for 1 year and their outcome
      observed. RESULTS: After 1 year, patients who had ToM deficit in a second order
      false question relapsed significantly more frequently as compared with patients
      who did not have a deficit (Fisher's exact test p < 0.0001; relative risk (RR) =
      8.105; CI 2.020, 32.524). Significant differences were shown in scores of the
      Global Assessment of Functioning Scale (p < 0.0001) between the two groups.
      CONCLUSIONS: Patients with ToM deficit in second order false belief during
      remission may be a high risk group for recurrence and lower social function 1
      year after recovering from a major depressive episode.

PMID- 16797083
TI  - Increased interleukin-1beta mRNA expression in skin biopsies of horses with
      Culicoides hypersensitivity following challenge with Culicoides nubeculosus
      extract.
AB  - Interleukin-1beta (IL-1beta) is a primary cytokine of the skin that has a pivotal
      role in keratinocyte differentiation, epidermal wound healing and host defense.
      Pathological increase of cutaneous IL-1beta is associated with edema formation,
      epidermal hyperproliferation and atopic dermatitis in humans. However, in horses
      the role of cutaneous IL-1beta in edema formation and allergic skin disease has
      not been characterised so far. Particularly in Culicoides hypersensitivity (CHS),
      intradermal injection of Culicoides extract may be associated with enhanced
      transcription of local IL-1beta. To examine the mRNA expression of IL-1beta and
      its receptor antagonist IL-1RA in the skin of horses, biopsy specimens of horses
      affected and non-affected by CHS prior and following intradermal challenge with a
      commercial C. nubeculosus extract were examined. Our hypothesis was that
      cutaneous IL-1beta mRNA was significantly upregulated in horses with CHS in
      response to Culicoides allergen. Biopsies were taken from sites prior to and 4 h
      following intradermal challenge with C. nubeculosus extract. 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. No significant difference was detected in non-challenged cutaneous
      IL-1beta mRNA and IL-1RA mRNA levels between CHS affected and non-affected
      horses. Intradermal injection of C. nubeculosus extract resulted in local
      upregulation of IL-1beta mRNA both in horses with typical history, characteristic
      clinical signs for CHS and a positive intradermal skin test (IDT), and non
      affected horses with a negative IDT. However, the difference in prior and post
      challenged site IL-1beta mRNA levels only reached statistical significance in the
      affected horses (p=0.01 versus 0.7). In contrast, IL-1RA mRNA levels did not
      demonstrate any modification following intradermal injection with C. nubeculosus
      in either group. In contrast to human atopic dermatitis, clinically normal skin
      of horses affected by CHS is not characterized by increased maintenance levels of
      IL-1beta mRNA. C. nubeculosus stimulates local IL-1beta transcription in all
      horses independent from disease, but the extent of upregulation from basal levels
      only reaches statistical significance in horses affected by CHS and active stage
      of disease.

PMID- 16797084
TI  - Identification and gene expression of the bovine C-type lectin Dectin-1.
AB  - C-type lectin receptors (CTLR) are cell-surface signalling molecules that
      recognize a range of highly conserved pathogen molecules and instigate the
      appropriate immune response. Here, we report the cloning, sequencing, mapping and
      expression pattern of the bovine C-type lectin domain family 7, member A (CLEC7A;
      synonyms CLCSF12, Dectin-1). We identified two isoforms, similar to the human
      system, with a long and short neck. Overall, the organization of the two bovine
      CLEC7A genes is similar to that of humans and mice. The CLEC7A gene maps on Bos
      taurus chromosome 5 (BTA5). mRNA transcripts for CLEC7A were detected in bone
      marrow cells, monocytes, macrophages and dendritic cells and NK cells, but not in
      CD4(+) T-cells or CD21(+) B-cells. The increased knowledge of the genomic
      organization of the bovine CTLR genes may promote our understanding of their
      evolution and help in the identification of bovine genes underlying disease
      resistance traits.

PMID- 16797086
TI  - Sequelae of recurrent laryngeal nerve injury after patent ductus arteriosus
      ligation.
AB  - OBJECTIVES: To prospectively study the clinical course of neonates with vocal
      cord paralysis (VCP) after patent ductus arteriosus (PDA) ligation. METHODS: A
      prospective cohort study of all premature infants undergoing PDA ligation from
      March 2001 to February 2004. Flexible laryngoscopy was performed after extubation
      to assess vocal cord function. Data regarding patient characteristics, operative
      findings, post-operative endoscopic findings, and the subsequent clinical course
      were collected. RESULTS: One hundred patients were enrolled. Flexible
      laryngoscopy was performed on 61 patients. Median birth weight was 740 g,
      gestational age 25 weeks, and age at operation 23 days. Flexible laryngoscopy was
      performed at an average of 8 days after extubation. Seven cases of vocal cord
      paralysis were identified. Two had stridor and feeding difficulty requiring
      nasogastric feeding. Five of the seven had an average follow-up of 9 months after
      surgery. At last follow-up, endoscopically satisfactory compensation by the
      normal vocal cord was observed in all five patients. No patient had feeding
      problems. CONCLUSIONS: The majority of infants who can be successfully extubated
      after PDA ligation tend to be asymptomatic despite vocal cord paralysis.
      Compensation appears to occur rapidly, and patients generally have no *long-term
      problems with the airway or feeding.

PMID- 16797085
TI  - Longitudinal analysis of activation markers on monocyte subsets during the
      development of simian immunodeficiency virus encephalitis.
AB  - Lentiviral encephalitis has been hypothesized to be associated with altered
      monocyte migration into the brain. CD14(hi)/CD16(lo) and CD14(lo)/CD16(hi)
      monocytes were expanded during acute infection; however, this expansion was not
      unique or greater in macaques that developed encephalitis. The proportion of
      monocytes that expressed CD62L, HLA-DR, CD16, CD64, and CD40 varied during the
      course of infection in macaques that eventually developed encephalitis. Taken
      together, these results suggest that changes in the proportion of circulating
      activated monocytes are not predictive of development of encephalitis, but this
      does not rule out the importance of activated monocytes in the development of
      encephalitis.

PMID- 16797088
TI  - Artificial neural network algorithms for early diagnosis of acute myocardial
      infarction and prediction of infarct size in chest pain patients.
AB  - BACKGROUND: To prospectively validate artificial neural network (ANN)-algorithms
      for early diagnosis of myocardial infarction (AMI) and prediction of 'major
      infarct' size in patients with chest pain and without ECG changes diagnostic for
      AMI. METHODS: Results of early and frequent Stratus CS measurements of troponin I
      (TnI) and myoglobin in 310 patients were used to validate four prespecified ANN
      algorithms with use of cross-validation techniques. Two separate biochemical
      criteria for diagnosis of AMI were applied: TnI > or = 0.1 microg/L within 24 h
      ('TnI 0.1 AMI') and TnI > or = 0.4 microg/L within 24 h ('TnI 0.4 AMI'). To be
      considered clinically useful, the ANN-indications of AMI had to achieve a
      predefined positive predictive value (PPV) > or = 78% and a negative predictive
      value (NPV) > or = 94% at 2 h after admission. 'Major infarct' size was defined
      by peak levels of CK-MB within 24 h. RESULTS: For the best performing ANN
      algorithms, the PPV and NPV for the indication of 'TnI 0.1 AMI' were 87%
      (p=0.009) and 99% (p=0.0001) at 2 h, respectively. For the indication of 'TnI 0.4
      AMI', the PPV and NPV were 90% (p=0.006) and 99% (p=0.0004), respectively.
      Another ANN-algorithm predicted 'major AMI' at 2 h with a sensitivity of 96% and
      a specificity of 78%. Corresponding PPV and NPV were 73% and 97%, respectively.
      CONCLUSIONS: Specially designed ANN-algorithms allow diagnosis of AMI within 2 h
      of monitoring. These algorithms also allow early prediction of 'major AMI' size
      and could thus, be used as a valuable instrument for rapid assessment of chest
      pain patients.

PMID- 16797087
TI  - Gene transfer system derived from the caprine arthritis-encephalitis lentivirus.
AB  - Lentiviruses are attractive candidates for therapeutic vectors, because of their
      ability to infect non-dividing target cells. Vectors based on HIV-1 efficiently
      transfer gene expression to a variety of dividing or quiescent cells, but are
      subject to reservations on safety grounds. Caprine arthritis encephalitis virus
      (CAEV) is a lentivirus inducing only minor pathology in its natural host and in
      related species after cross-species transmission. To test the CAEV potential as
      vector for gene transfer, a cassette expressing the green fluorescent protein
      (GFP) under control of a CMV promoter was inserted into the CAEV genome,
      producing the pK2EGFPH vector. When pseudotyped with vesicular stomatitis virus
      (VSV)-G envelope protein, this vector allowed efficient transfer of GFP
      expression in human cells (up to 86% of GFP-expressing cells into the TE671 cell
      line). Three vectors carrying different parts of the viral gag, pol and env genes
      were then developed, together with a CAEV packaging system. These vectors allowed
      delimitation of the minimal CAEV sequences necessary for an improvement of vector
      production compared to the previously described CAEV-based vectors [Mselli-Lakhal
      et al., 1998. Defect in RNA transport and packaging are responsible for low
      transduction efficiency of CAEV-based vectors. Arc. Virol. 143, 681-695]. While
      our previous vectors were produced in a helper/vector system, the present vectors
      are produced in a helper/free system. However, these vector titers remain lower
      than those obtained with other lentiviral vectors carrying equivalent packaging
      sequences. We discuss on possible reasons of such differences and possible
      improvements.

PMID- 16797089
TI  - Improved right ventricular-vascular coupling during active pulmonary
      hypertension.
AB  - Right ventricular adaptation to pulmonary hypertension (PH) is an important
      prognostic factor. Pulmonary artery (PA) smooth muscle activation attenuates
      arterial dysfunction during acute PH. We investigated the role of the pulmonary
      artery vascular smooth muscle activation on the right ventricular-vascular
      coupling during acute PH. PA flow, pressure, and diameter, right ventricular and
      aortic pressures were recorded in six anesthetized sheep. Acute PH was induced by
      phenylephrine (APH) and PA mechanical constriction (PPH). We calculated the PA
      buffering function, the incremental elastic modulus and pulmonary vascular
      compliance. Pulmonary vascular impedance and right ventricular hydraulic power
      were calculated through Fourier approach. We also quantified the magnitude and
      timing of the reflected wave. Right ventricular-vascular coupling was assessed by
      the energy transmission ratio. Pulmonary buffering function and vascular
      compliance increased (P<0.05) and arterial wall stiffness decreased (P<0.05)
      during APH with respect to PPH. Although total input resistance increased and
      reflected wave came back earlier during PH states (P<0.05), only PPH produced a
      rightward shift of the pulmonary impedance and a more prominent reflected wave.
      Accordingly, APH determined a minor increase of total hydraulic power with a
      smaller pulsatile to total power ratio and energy transmission ratio (P<0.05). In
      conclusion, isobaric PA vasoconstriction prevents the pulsatile hydraulic load to
      increase by preserving the PA buffering function and the reflected wave
      magnitude. Thus, vascular smooth muscle activation of the main PA improves the
      energy transfer from the right ventricle to the hypertensive pulmonary
      circulation, and this may play relevant role in the right ventricular adaptation
      to acute PH.

PMID- 16797090
TI  - Possible contribution of pericardial tamponade to coronary artery bypass graft
      occlusion.
AB  - We report an association between pericardial tamponade and early post-surgical
      occlusion of a coronary bypass graft. The presented patient developed
      pericarditis following myocardial infarction and bypass surgery. He was
      readmitted with myocardial reinfarction and cardiogenic shock 1 week after
      surgery. Coronary angiography revealed occlusion of a saphenous-vein graft to the
      right coronary artery. Concomitantly, pericardial tamponade was diagnosed on the
      basis of typical hemodynamics and echocardiographic findings. The patient
      recovered following pericardiocentesis and coronary angioplasty. We suggest a
      possible link between the 2 pathologies, whereby post-surgical pericarditis led
      to tamponade which decreased cardiac preload and resulted in systemic
      hypotension. Decreased coronary perfusion pressure and extrinsic compression by
      fluid in the pericardial space may have contributed to graft occlusion.
      Pericarditis and pericardial tamponade may therefore be risk factors for coronary
      bypass graft occlusion.

PMID- 16797091
TI  - Suboptimal medical therapy in patients with systolic heart failure is associated
      with less improvement by cardiac resynchronization therapy.
AB  - BACKGROUND: Proven medical therapy is under-prescribed in heart failure (HF) for
      various reasons. Cardiac resynchronization therapy (CRT) is of proven value in
      selected patients with HF; however, the degree of benefit in those without the
      optimal therapy is not clear. METHODS: This is a retrospective study comparing
      the effect of CRT in 30 patients without optimal combination therapy (group 1; 10
      (33%) without ACEi or equivalent and 25 (83%) without beta-blockers) to an age,
      sex, ejection fraction (EF) and New York Heart Association (NYHA) class matched
      control but with the combination (group 2; n=30) at baseline. All patients were
      in NYHA class III or IV with EF < or = 35% and QRS interval > or = 120 ms.
      Echocardiographic examination and N-terminal pro-brain natriuretic peptide (NT
      pro-BNP) levels before and 3 months after CRT were compared between the two
      groups. The composite endpoints of HF hospitalization or death during follow-up
      were compared by Kaplan-Meier analysis. RESULTS: There were significantly less
      improvement in EF (+4.0+/-2.5% vs +10.1+/-3.2%; p<0.05) and degree of reverse
      remodeling in group 1 after 3 months. Patients in group 1 had significantly
      higher level of NT pro-BNP levels at 3 months (2221+/-2001 pg/mL vs 1038+/-905
      pg/mL; p<0.001) and higher rates of HF hospitalization or death (53.3% vs 23.3%;
      Log rank chi2 5.52; p=0.019). CONCLUSION: Patients receiving CRT but without
      optimal medical therapy were associated with less echocardiographic and clinical
      improvement. Optimal medical therapy, if tolerated, before CRT is necessary.

PMID- 16797093
TI  - A stochastic exposure assessment model to estimate vanadium intake by beef cattle
      used as sentinels for the South African vanadium mining industry.
AB  - This paper presents an environmental exposure assessment model for estimating
      chronic intake of vanadium (a transition metal) by cattle farmed extensively in
      areas contaminated by vanadium pollutants. The exposure model differs from most
      other models in several ways: (1) it does not rely heavily on extrapolating
      information from the point source (e.g. stack height, exit velocity, exit
      diameter) to the point of exposure. (2) It incorporates the physiological
      constraints of the species exposed. (3) It takes into account oral as well as
      inhalation exposure. (4) It addresses terrain, by using measurements at the point
      of exposure. (5) It accounts for existing background concentrations of pollutants
      and pollutants from multiple sources. (6) It uses a stochastic process with
      distribution functions to account for variability in the data over time.
      Environmental inputs into the model included aerial fall-out sample vanadium
      (n=566), unwashed grass sample vanadium (n=342) and soluble soil sample vanadium
      (n=342). Physiological cattle inputs were derived from two cohorts of Brahman
      cross sentinel cattle (n=30). The model provided an estimate of the chronic
      external exposure dose of vanadium for two separate groups of cattle grazing over
      a 5-year period (1999-2004) immediately adjacent (median dose=2.14mg vanadium/kg
      body weight/day) and 2km away (median dose=1.07mg/kg/day) from a South African
      vanadium-processing plant, respectively. The final output of the model is a
      distribution curve of the probable vanadium intake based on the variability
      within the inputs over the 5-year period of the study. The model is adaptable
      enough for application to other transition metals and species (including man),
      and could be used as an alternative to plume-dispersion modelling.

PMID- 16797094
TI  - Guidelines for primary radiotherapy of patients with prostate cancer.
AB  - BACKGROUND AND PURPOSES: The appropriate application of 3-D conformal
      radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for
      patients undergoing radiotherapy for prostate cancer requires a standardisation
      of target delineation as well as clinical quality assurance procedures. PATIENTS
      AND METHODS: Pathological and imaging studies provide valuable information on
      tumour extension. In addition, clinical investigations on patient positioning and
      immobilisation as well as treatment verification data offer an abundance of
      information. RESULTS: Target volume definitions for different risk groups of
      prostate cancer patients based on pathological and imaging studies are provided.
      Available imaging modalities, patient positioning and treatment preparation
      studies as well as verification procedures are collected from literature studies.
      These studies are summarised and recommendations are given where appropriate.
      CONCLUSIONS: On behalf of the European Organisation for Research and Treatment of
      Cancer (EORTC) Radiation Oncology Group this article presents a common set of
      recommendations for external beam radiotherapy of patients with prostate cancer.

PMID- 16797095
TI  - Notes on the construction of solid-state detectors.
AB  - BACKGROUND AND PURPOSE: Solid-state detectors such as diodes and diamonds are
      useful radiation detectors, particularly for small field measurements, such as in
      stereotactic dosimetry or in the small sub-field measurements required for
      intensity modulated radiotherapy (IMRT) . In all small field measurements,
      positioning of the detector is critical. Generally it is assumed that the center
      of the sensitive volume of each solid-state detector is coincident with the
      geometric center of the outer casing. PATIENTS AND METHODS: X-rays were taken of
      four detectors (diamond, three types of diode) to determine the physical
      characteristics of each, particularly the position of the centre of the sensitive
      volume. RESULTS: The results showed that the position of the centre of the
      sensitive volume is not always coincident with the geometric centre of a solid
      state detector. CONCLUSIONS: The construction of a detector used for precise
      measurements should be investigated prior to use, by taking high resolution x-ray
      images.

PMID- 16797096
TI  - Delusions: A suitable case for imaging?
AB  - This review is intended to outline the need/opportunities for imaging research in
      the area of delusions. In particular, delusions of misidentification are offered
      as possible examples of how both spatial and temporal brain imaging may throw
      light upon the theoretical, parallel processes of identification and emotional
      arousal occurring when a familiar face is encountered. Other types of Delusional
      Misidentifications are also briefly explored. The review then turns to related
      phenomena, including the ways imaging may help elucidate different types of
      covert face recognition; and also further explain the distinctive (but not
      entirely independent) processes underlying face, voice and object recognition.
      Throughout the review the aim is to emphasise the potential value to cognitive
      neuropsychiatry of good imaging techniques.

PMID- 16797092
TI  - Effect of agro-ecological zone and grazing system on incidence of East Coast
      Fever in calves in Mbale and Sironko Districts of Eastern Uganda.
AB  - Between May 2002 and February 2003 a longitudinal survey was carried out in Mbale
      and Sironko Districts of Eastern Uganda to determine the influence of agro
      ecological zones (AEZ) and grazing systems on tick infestation patterns and
      incidence of East Coast Fever (ECF) in bovine calves. The study area was
      stratified into AEZ (lowland, midland and upland) and grazing systems {zero
      grazing (ZG), restricted-outdoor grazing (ROG) and communal grazing (CG)}, whose
      strata had previously been shown to influence the prevalence of ECF, babesiosis
      and anaplasmosis. One hundred and eighty-five smallholder dairy farms with a
      total of 198 calves of both sexes, between the ages of 1 day and 6 weeks, were
      purposively selected from the AEZ-grazing system strata. Nine dynamic cohorts (11
      51 calves in each) of these calves were examined and sampled monthly. Ticks
      infesting the calves were counted from one side of the animal body and
      categorized into the different species, sex and feeding status. Sera were
      collected at recruitment and monthly thereafter and antibodies against Theileria
      parva, T. mutans, Babesia bigemina, B. bovis and Anaplasma marginale were
      measured using ELISA. Tick challenge (total and specific) varied with AEZ and
      grazing system. The risk of infection with T. parva was higher in the lowland
      zone compared to the upland zone (hazard ratio (HR)=2.59; 95% CI: 1.00-6.34). The
      risk of infection with T. parva was higher in the CG system than the ZG system
      (HR=10.00; 95% CI: 3.61-27.92). The incidence risk for sero-conversion, over the
      10 months study period, was 62, 16 and 9% in the lowland, midland and upland
      zones, respectively. Ninety-eight percent of the calves in lowland-CG stratum
      sero-converted by the age of 6 months, while 56 and 8% did so in the lowland-ROG
      and the lowland-ZG stratum, respectively. The results of this study show the need
      to consider farm circumstances and the variation in ECF risk, both spatially and
      temporally when designing control strategies for ECF.

PMID- 16797097
TI  - Single-step purification of recombinant anthrax lethal factor from periplasm of
      Escherichia coli.
AB  - Lethal toxin (LT) that composed by protective antigen and lethal factor (LF) is
      the major virulence factor of Bacillus anthracis. The treatments of LT in animals
      could reproduce most manifestations of B. anthracis infections that greatly
      improves our knowledge in LT-mediated pathogenesis and facilitates anthrax
      related researches without having to directly contact the hazardous bacterium B.
      anthracis. The recombinant protein of LF (rLF), however, still lacks a simple
      purification method. Herein, we developed single-step nickel affinity
      purification of rLF with yield up to 3mg/l. By fusion to the leader sequence of
      outer membrane protein OmpA, rLF could easily be purified from the periplasm of
      Escherichia coli. To investigate whether the rLT is functional in our system,
      both wild type rLF and the catalytic mutant rLF that contains a single amino acid
      substitution at zinc-binding site (LF(E687A)), were subjected to macrophage
      cytotoxicity analysis. Our data showed that the rLT is fully functional, while
      the LF(E687A) fail to induce cell death of tested macrophage cells. These
      findings suggested that the purification protocol herein is a user-friendly
      method that allows researchers to obtain the functional rLF by single-step
      purification.

PMID- 16797098
TI  - A model for the drug release from a polymer matrix tablet--effects of swelling
      and dissolution.
AB  - A model for simulating the drug release from a swelling and dissolving polymer
      tablet is presented and verified to data. The model is based on a mechanistic
      approach, and it can therefore be employed to study the sensitivity of true
      physical constants, for instance the drug diffusion coefficient or the drug
      solubility. The model generates the drug and polymer release profiles and the
      front positions of the total tablet, the solid core, and of the solid-drug
      solubilized-drug interface. The convective contribution to mass transfer is shown
      to be of great importance. This is most markedly noticed for slowly diffusing
      drugs. In a simulation with a low value of the drug diffusion coefficient, it is
      shown that the initial drug release rate is faster than the polymer dissolution
      rate, followed by a second stage with a slower drug release rate. Furthermore, it
      is shown that polymer dissolution influences the drug release profile
      significantly, but not the front position of saturated drug in the gel layer. The
      model is verified against drug release and polymer dissolution data for the
      slightly soluble drug Methyl paraben and the soluble drug Saligenin in a poly
      (ethylene oxide) tablet, resulting in good agreement between model and
      experiments.

PMID- 16797099
TI  - Non-viral adiponectin gene therapy into obese type 2 diabetic mice ameliorates
      insulin resistance.
AB  - Synthetic polymer vectors are attractive for gene delivery due to their potential
      safety and versatility. However, due to the low efficiency, most of the
      successful applications of polymeric vectors are focused on the therapeutic genes
      whose products have biological effects at low concentrations. Adiponectin is one
      of the abundant circulating proteins and possesses diverse effects including anti
      hyperglycemic and anti-atherogenic properties. In this study, we performed the
      adiponectin gene delivery using a mini-circle DNA complexed with a polymeric
      carrier, polyethylenimine, into diet induced obese C57BL/6J mice. The mini-circle
      DNA showed much higher adiponectin expression than the conventional plasmid in
      vitro and in vivo. This strategy achieved a sufficient blood level of adiponectin
      and the parameters related with insulin resistance were normalized. The mini
      circle DNA will be useful for the increased efficiency of polymeric vectors and
      adiponectin gene therapy which is applicable to the treatment of type 2 diabetes.

PMID- 16797100
TI  - Liver stiffness measurement selects patients with cirrhosis at risk of bearing
      large oesophageal varices.
AB  - BACKGROUND/AIMS: Periodic endoscopic screening for oesophageal varices is
      recommended in patients with cirrhosis, but might be limited to a subgroup of
      patients if a simple non-invasive test was available to select those at risk of
      bleeding. METHODS: We studied in 165 patients with cirrhosis the relation between
      the presence of oesophageal varices assessed by endoscopy, and liver stiffness
      measurement by Fibroscan, a non-invasive parameter related to liver fibrosis. The
      results were compared to those of other parameters reflecting portal
      hypertension, splenic size, platelet count, and platelet count/spleen size ratio.
      RESULTS: Liver stiffness measurement was correlated to the grade of oesophageal
      varices (r = 0.6, p < 0.0001). AUROC values of liver stiffness measurement were
      0.84 (95% CI: 0.78-0.90) for the presence of oesophageal varices and 0.83 (0.76
      0.89) for varices grade > or = II. Liver stiffness measurement value < 19 kPa was
      highly predictive of the absence of oesophageal varices grade > or = II (Se: 84%,
      PPV: 47%, NPV: 93%). CONCLUSIONS: Liver stiffness measurement allows to predict
      the presence of large oesophageal varices in patients with cirrhosis, and may
      help to select patients for endoscopic screening.

PMID- 16797101
TI  - Antiviral effect of peginterferon alfa-2b and alfa-2a compared.

PMID- 16797102
TI  - The registration of CT image to the patient head by using an automated laser
      surface scanning system--a phantom study.
AB  - In this paper, a practical methodology of surface-based registration supported by
      an automated laser surface scanning system to achieve good mapping performance is
      reported. The laser scanning system is used to digitize the facial feature of a
      phantom so as to mesh the physical space into triangular frame. The image space
      is established by translating the corresponding CT image into point set through
      using the medical image software tools. The image-to-physical registration task
      is carried out by a direct searching mechanism together with the objective
      function in an optimal fashion. The unconstrained nonlinear optimization
      algorithm performs the optimal searching iteration to find those parameters in
      the rigid-body transformation until the sum of the squared normal distances is
      minimized. Considering mapping the massive points in registration task would
      consume the computation time, there is only a suitable sample size to stand for
      the entire population with sufficient confidence and accuracy are extracted
      statistically from the CT point space to map to the laser scanning space.
      Registration results evaluated by gauging the position errors of the landmarks on
      phantom forehead show the proposed methodology has good ability to perform the
      image-to-physical registration.

PMID- 16797103
TI  - Analysis of a mesoscale infiltration and water seepage test in unsaturated
      fractured rock: Spatial variabilities and discrete fracture patterns.
AB  - A mesoscale (21 m in flow distance) infiltration and seepage test was recently
      conducted in a deep, unsaturated fractured rock system at the crossover point of
      two underground tunnels. Water was released from a 3 mx4 m infiltration plot on
      the floor of an alcove in the upper tunnel, and seepage was collected from the
      ceiling of a niche in the lower tunnel. Significant temporal and (particularly)
      spatial variabilities were observed in both measured infiltration and seepage
      rates. To analyze the test results, a three-dimensional unsaturated flow model
      was used. A column-based scheme was developed to capture heterogeneous hydraulic
      properties reflected by these spatial variabilities observed. Fracture
      permeability and van Genuchten alpha parameter [van Genuchten, M.T., 1980. A
      closed-form equation for predicting the hydraulic conductivity of unsaturated
      soils. Soil Sci. Soc. Am. J. 44, 892-898] were calibrated for each rock column in
      the upper and lower hydrogeologic units in the test bed. The calibrated fracture
      properties for the infiltration and seepage zone enabled a good match between
      simulated and measured (spatially varying) seepage rates. The numerical model was
      also able to capture the general trend of the highly transient seepage processes
      through a discrete fracture network. The calibrated properties and measured
      infiltration/seepage rates were further compared with mapped discrete fracture
      patterns at the top and bottom boundaries. The measured infiltration rates and
      calibrated fracture permeability of the upper unit were found to be partially
      controlled by the fracture patterns on the infiltration plot (as indicated by
      their positive correlations with fracture density). However, no correlation could
      be established between measured seepage rates and density of fractures mapped on
      the niche ceiling. This lack of correlation indicates the complexity of
      (preferential) unsaturated flow within the discrete fracture network. This also
      indicates that continuum-based modeling of unsaturated flow in fractured rock at
      mesoscale or a larger scale is not necessarily conditional explicitly on discrete
      fracture patterns.

PMID- 16797104
TI  - Investigating the role of gas bubble formation and entrapment in contaminated
      aquifers: Reactive transport modelling.
AB  - In many natural and contaminated aquifers, geochemical processes result in the
      production or consumption of dissolved gases. In cases where methanogenesis or
      denitrification occurs, the production of gases may result in the formation and
      growth of gas bubbles below the water table. Near the water table, entrapment of
      atmospheric gases during water table rise may provide a significant source of
      O(2) to waters otherwise depleted in O(2). Furthermore, the presence of bubbles
      will affect the hydraulic conductivity of an aquifer, resulting in changes to the
      groundwater flow regime. The interactions between physical transport,
      biogeochemical processes, and gas bubble formation, entrapment and release is
      complex and requires suitable analysis tools. The objective of the present work
      is the development of a numerical model capable of quantitatively assessing these
      processes. The multicomponent reactive transport code MIN3P has been enhanced to
      simulate bubble growth and contraction due to in-situ gas production or
      consumption, bubble entrapment due to water table rise and subsequent re
      equilibration of the bubble with ambient groundwater, and permeability changes
      due to trapped gas phase saturation. The resulting formulation allows for the
      investigation of complex geochemical systems where microbially mediated redox
      reactions both produce and consume gases as well as affect solution chemistry,
      alkalinity, and pH. The enhanced model has been used to simulate processes in a
      petroleum hydrocarbon contaminated aquifer where methanogenesis is an important
      redox process. The simulations are constrained by data from a crude oil spill
      site near Bemidji, MN. Our results suggest that permeability reduction in the
      methanogenic zone due to in-situ formation of gas bubbles, and dissolution of
      entrapped atmospheric bubbles near the water table, both work to attenuate the
      dissolved gas plume emanating from the source zone. Furthermore, the simulations
      demonstrate that under the given conditions more than 50% of all produced CH(4)
      partitions to the gas phase or is aerobically oxidised near the water table,
      suggesting that these processes should be accounted for when assessing the rate
      and extent of methanogenic degradation of hydrocarbons.

PMID- 16797105
TI  - The biological activity of the histidine-containing diketopiperazines cyclo(His
      Ala) and cyclo(His-Gly).
AB  - Two cyclic dipeptides, cyclo(His-Ala) and cyclo(His-Gly,) were synthesized from
      their linear counterparts and their structures elucidated using standard
      elucidation techniques. Molecular modeling and predictive NMR results indicated
      that the majority of energetically favourable conformers adopted a boat
      conformation with respect to the diketopiperazine ring. Cyclo(His-Ala), at
      concentrations of 100 microM inhibited the growth, in vitro, of various cancer
      cell lines, including HT-29, MCF-7 and HeLa carcinoma cells while cyclo(His-Gly)
      inhibited the growth of MCF-7 cells. While the antibacterial potential of these
      two compounds was limited, both cyclic dipeptides significantly inhibited the
      growth of C. albicans. Both compounds at a concentration of 100 microM resulted
      in a decrease in heart rate, coronary flow rate and left ventricular systolic
      pressure in the isolated rat heart. Inhibition of thrombin, amounting to a 63.3%
      and 36.7% reduction in the rate of fibrin formation, was noted for cyclo(His-Ala)
      and cyclo(His-Gly), respectively. While cyclo(His-Ala) showed no notable effects
      on platelet aggregation, cyclo(His-Gly) significantly inhibited both pathways
      tested with greatest effects on thrombin-induced platelet aggregation, yielding
      an IC(50) of 0.0662 mM (R(2)=0.989). The results of the anticancer and
      hematological studies indicate that histidine-containing diketopiperazines have
      potential as a novel group of cytotoxic agents with antithrombotic effects.

PMID- 16797106
TI  - Experimental study on the efficacy of combination of alpha-helical antimicrobial
      peptides and vancomycin against Staphylococcus aureus with intermediate
      resistance to glycopeptides.
AB  - An experimental study has been performed to compare the in vitro activity and the
      in vivo efficacy of magainin II and cecropin A, two alpha-helical antimicrobial
      peptides, and vancomycin against Staphylococcus aureus with intermediate
      resistance to glycopeptides. In vitro experiments included MIC determination,
      time-kill and synergy studies. For in vivo studies, a mouse model of
      staphylococcal sepsis has been used. Main outcome measures were: lethality,
      quantitative blood cultures and detection of TNF-alpha and interleukin-6 (IL-6)
      plasma levels. Combinations of alpha-helical antimicrobial peptides showed in
      vitro synergistic interaction. Significant increase in efficacy was also observed
      in vivo: combined-treated groups had significant lower bacteremia when compared
      to single-treated groups. Magainin II combined with vancomycin exhibited the
      highest efficacy on all main outcome measurements. These results highlight the
      potential usefulness of these combinations and provide future therapeutic
      alternative in infections due to glycopeptides resistant staphylococci in the
      coming years.

PMID- 16797107
TI  - Adrenomedullin antagonizes angiotensin II-stimulated proliferation of human
      aortic smooth muscle cells.
AB  - The vasodilating peptide adrenomedullin has been reported to regulate vascular
      tone as well as proliferation and differentiation of various cell types in an
      autocrine/paracrine manner. Conflicting data have been reported on the
      adrenomedullin (AM) effect on vascular smooth muscle cell proliferation, a
      process involved in the progression of vascular remodeling and atherosclerotic
      lesion. In this paper we investigate the effect of AM on proliferation of human
      aorta smooth muscle cell (HASMC). AM showed a potent dose-dependent inhibiting
      effect on angiotensin II (AngII) induced-proliferation and a stimulatory effect
      on proliferation of quiescent cells. The cAMP/PKA pathway was involved in the AM
      inhibitory effect of AngII-induced proliferation in HASMC. PI3K/Akt and ERK
      pathways were involved in the proliferative effect exerted by AM per se. Our
      results suggest that AM plays a role in the regulation of HASMC growth
      antagonizing the AngII effect and may be involved in conditions of altered
      regulation of the blood vessels.

PMID- 16797108
TI  - [Cytomegalovirus myelitis in immunocompetent adult].
AB  - INTRODUCTION: Cytomegalovirus (CMV) infection occurs in 40 to 100% of general
      population. It is often asymptomatic in immunocompetent subject but may induce
      neurological syndromes such as encephalitis and myelitis. CASE RECORD: We
      reported a case of a 64-years-old woman immunocompetent, with acute proximal
      upper and lower limb weakness, paresthesias and two episodes of urinary
      retention. MRI of the spine showed abnormal enhancement from cervical to lumbar
      spine indicative for myelitis. Diagnosis of CMV associated myelitis was confirmed
      by a positive CMV serology. Administration of ganciclovir was followed by a
      partial improvement in five months. DISCUSSION: Few cases of CMV acute myelitis
      in immunocompetent patients have been reported in the literature. The
      pathogenesis is not well known, however, immune-mediated central nervous system
      damage may be attributed to the pathogenesis of the disease. Early diagnosis and
      treatment improves the prognosis.

PMID- 16797109
TI  - The European CHMP criteria for influenza vaccine immunogenicity cannot be
      improved by the use of confidence intervals.
AB  - In a well-know CHMP Note for Guidance criteria are given for evaluation the
      results of annual-update studies. Now and then it sometimes is suggested that
      these criteria can be improved by the use of confidence intervals. Here it is
      argued that this is based on a misinterpretation of what confidence intervals
      are. These intervals require that subjects are chosen at random from a
      population. In influenza studies this is never the case.

PMID- 16797110
TI  - Development of H5-RT-LAMP (loop-mediated isothermal amplification) system for
      rapid diagnosis of H5 avian influenza virus infection.
AB  - We developed a rapid and sensitive diagnosis system for H5N1 highly pathogenic
      avian influenza (HPAI) virus infection using an unique gene amplification method,
      reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). The
      sensitivity of the system was found to be 100-fold higher than that of ordinary
      one-step RT-PCR. Moreover, by using viral RNAs extracted from influenza viruses
      of all 15 HA subtypes, the RT-LAMP system was confirmed to amplify only the RNA
      of H5 subtype virus. In the surveillance of H5N1 virus infection of wild birds,
      we detected two positive cases from dead crows found near the affected area with
      H5N1-HPAI by using RT-LAMP system, although one of two positive cases was missed
      by RT-PCR. These results suggested that our newly developed RT-LAMP system
      specific for H5 virus would be a beneficial diagnostic tool for surveillance of
      recent outbreaks caused by H5N1-HPAI viruses.

PMID- 16797111
TI  - Lead and cadmium in leaves of deciduous trees in Beijing, China: development of a
      metal accumulation index (MAI).
AB  - Lead and cadmium uptake was investigated for common deciduous street trees in
      Beijing in this study. Species having Cd accumulation included Populus tomentosa,
      Sophora japonica and Catalpa speciosa. P. tomentosa had the highest ratios
      between leaf and soil Cd (0.848), followed by S. japonica (0.536), C. speciosa
      (0.493), Paulownia tomentosa (0.453) and Juglans regia (0.415). Pb levels were
      high in leaves of C. speciosa, J. regia and Pa. tomentosa. S. japonica had the
      highest ratio between leaf Pb and soil Pb (0.146), followed by Pa. tomentosa
      (0.143), Ginko biloba (0.103) and C. speciosa (0.095). A predictive foliar metal
      accumulation index (MAI) was developed and C. speciosa was calculated to have the
      highest MAI value (53.8). This suggests that C. speciosa would be a good choice
      for planting in areas of Beijing where soil contamination with Cd and Pb may be a
      problem.

PMID- 16797112
TI  - Genome-wide transcriptome profiling of the early cadmium response of Arabidopsis
      roots and shoots.
AB  - Transcriptional regulation in response to cadmium treatment was investigated in
      both roots and leaves of Arabidopsis, using the whole genome CATMA microarray
      containing at least 24,576 independent probe sets. Arabidopsis plants were
      hydroponically treated with low (5 microM) or high (50 microM) cadmium
      concentrations during 2, 6, and 30 hours. At each time point, Cd level was
      determined using ICP-AES showing that both plant tissues are able to accumulate
      the heavy metal. RT-PCR of eight randomly selected genes confirmed the
      reliability of our microarray results. Analyses of response profiles demonstrate
      the existence of a regulatory network that differentially modulates gene
      expression in a tissue- and kinetic-specific manner in response to cadmium. One
      of the main response observed in roots was the induction of genes involved in
      sulfur assimilation-reduction and glutathione (GSH) metabolism. In addition, HPLC
      analysis of GSH and phytochelatin (PC) content shows a transient decrease of GSH
      after 2 and 6 h of metal treatment in roots correlated with an increase of PC
      contents. Altogether, our results suggest that to cope with cadmium, plants
      activate the sulfur assimilation pathway by increasing transcription of related
      genes to provide an enhanced supply of GSH for PC biosynthesis. Interestingly, in
      leaves an early induction of several genes encoding enzymes involved in the
      biosynthesis of phenylpropanoids was observed. Finally, our results provide new
      insights to understand the molecular mechanisms involved in transcriptional
      regulation in response to cadmium exposure in plants.

PMID- 16797113
TI  - Class-1 release factor eRF1 promotes GTP binding by class-2 release factor eRF3.
AB  - In eukaryotes, termination of mRNA translation is triggered by the essential
      polypeptide chain release factors eRF1, recognizing all three stop codons, and
      eRF3, a member of the GTPase superfamily with a role that has remained opaque. We
      have studied the kinetic and thermodynamic parameters of the interactions between
      eRF3 and GTP, GDP and the non-hydrolysable GTP analogue GDPNP in the presence
      (K(D)(GDP)=1.3+/-0.2 muM, K(D)(GTP) approximately 200 muM and K(D)(GDPNP)>160
      muM) as well as absence (K(D)(GDP)=1.9+/-0.3 muM, K(D)(GTP) 0.7+/-0.2 muM and
      K(D)(GDPNP) approximately 200 muM) of eRF1. From the present data we propose that
      (i) free eRF3 has a strong preference to bind GDP compared to GTP (ii) eRF3 in
      complex with eRF1 has much stronger affinity to GTP than free eRF3 (iii) eRF3 in
      complex with PABP has weak affinity to GTP (iv) eRF3 in complex with eRF1 does
      not have strong affinity to GDPNP, implying that GDPNP is a poor analogue of GTP
      for eRF3 binding.

PMID- 16797114
TI  - A simple visual analogue scale to assess the quality of life in women with
      urinary incontinence.
AB  - AIM: The objective of this study is to determine whether a simple visual analogue
      scale; "incontinence bothersome scale (IBS)" can reliably assess the quality of
      life in women with urinary incontinence. DESIGN: A prospective cohort study in a
      UK district general hospital. METHODS: Two hundreds women with urinary
      incontinence participated in the study over 1-year period. They completed Kings
      health questionnaire version 7 (KHQ) and the incontinence bothersome scale (IBS).
      The results of the IBS were then compared to the total KHQ score and to each
      domain separately, using the Pearson correlation test. Women in the study were
      then classified into two main groups according to their urodynamics diagnosis
      (urodynamic stress incontinence group/detrusor overactivity group) and the total
      KHQ scores were compared with the IBS scores in each group. RESULTS: The IBS
      scores had poor correlation with the total KHQ scores (r=0.656) and the
      difference between both arms was not statistically significant (p=0.084). Further
      analysis of KHQ domains showed that except for the impact of incontinence domain
      (r=0.728) all other domains correlated poorly to the IBS. This poor correlation
      pertained in sub-analysis of women with DO and USI (r=0.65 and 0.48,
      respectively). CONCLUSION: This study has shown that a simple visual scale is not
      a reliable tool in assessing the QoL in women with urinary incontinence. A
      formal, validated and reliable QoL questionnaire is still the method of choice
      for QoL assessment, even if it takes longer to complete.

PMID- 16797115
TI  - Compartmentalization of the Type I Fc epsilon receptor and MAFA on mast cell
      membranes.
AB  - The Mast cell Function-associated Antigen (MAFA) is a membrane glycoprotein on
      rat mast cells (RBL-2H3) expressed at a ratio of approximately 1:30 with respect
      to the Type I Fc epsilon receptor (Fc epsilon RI). Despite this stoichiometry,
      clustering MAFA by its specific mAb G63 substantially inhibits secretion of both
      granular and de novo synthesized mediators induced upon Fc epsilon RI
      aggregation. Since the Fc epsilon RIs apparently signal from within raft micro
      environments, we investigated possible co-localization of MAFA within these
      membrane compartments containing aggregated Fc epsilon RI. We used cholera toxin
      B subunit (CTB) to cluster the raft component ganglioside GM1 and studied the
      effects of this perturbation on rotation of Fc epsilon RI and MAFA by time
      resolved phosphorescence anisotropy of erythrosin-conjugated probes. CTB
      treatment would be expected to substantially inhibit rotation of raft-associated
      molecules. Experimentally, CTB has no effect on rotational parameters such as the
      long-time anisotropy (r(infinity)) of unperturbed Fc epsilon RI or MAFA. However,
      on cells where Fc epsilon RI-IgE has previously been clustered by antigen
      (DNP(14)-BSA), CTB treatment increases the Fc epsilon RI-IgE's r(infinity) by
      0.010 and MAFA's by 0.014. Similarly, CTB treatment of cells where MAFA had been
      clustered by mAb G63 increases MAFA's r(infinity) by 0.010 but leaves Fc epsilon
      RI's unaffected. Evaluation of raft localization of Fc epsilon RI and MAFA using
      sucrose gradient ultracentrifugation of Triton X-100 treated membrane fragments
      demonstrates that a significant fraction of MAFA molecules sediments with rafts
      when Fc epsilon RI is clustered by antigen or when MAFA itself is clustered by
      mAb G63. The large excess of Fc epsilon RI over MAFA explains why clustering MAFA
      does not substantively affect Fc epsilon RI dynamics. Moreover, in single
      particle tracking studies of individual Fc epsilon RI-IgE or MAFA molecules,
      these proteins, upon clustering by antigen, move into small membrane compartments
      of reduced, but similar, dimensions. This provides additional indication of
      constitutive interactions between Fc epsilon RI and MAFA. Taken together, these
      results of distinct methodologies suggest that MAFA functions within raft
      microdomains of the RBL-2H3 cell membrane and thus in close proximity to the Fc
      epsilon RI which themselves signal from within the raft environment.

PMID- 16797116
TI  - Diffusion constant of K+ inside Gramicidin A: a comparative study of four
      computational methods.
AB  - The local diffusion constant of K(+) inside the Gramicidin A (GA) channel has
      been calculated using four computational methods based on molecular dynamics (MD)
      simulations, specifically: Mean Square Displacement (MSD), Velocity
      Autocorrelation Function (VACF), Second Fluctuation Dissipation Theorem (SFDT)
      and analysis of the Generalized Langevin Equation for a Harmonic Oscillator (GLE
      HO). All methods were first tested and compared for K(+) in bulk water--all
      predicted the correct diffusion constant. Inside GA, MSD and VACF methods were
      found to be unreliable because they are biased by the systematic force exerted by
      the membrane-channel system on the ion. SFDT and GLE-HO techniques properly
      unbias the influence of the systematic force on the diffusion properties and
      predicted a similar diffusion constant of K(+) inside GA, namely, ca. 10 times
      smaller than in the bulk. It was found that both SFDT and GLE-HO methods require
      extensive MD sampling on the order of tens of nanoseconds to predict a reliable
      diffusion constant of K(+) inside GA.

PMID- 16797117
TI  - Voiding symptom evaluation: it is time to recalibrate.

PMID- 16797118
TI  - Management of the spectrum of hormone refractory prostate cancer.
AB  - INTRODUCTION: In its advanced stages, hormone refractory prostate cancer (HRPC)
      is an incurable condition which consists of a spectrum of disease. This requires
      an integrated multidisciplinary approach by an uro-oncologic team supported by
      radiologists, skeletal surgeons and palliative care. Aim of this review was to
      critically evaluate the current and potential approaches to patients affected by
      HRPC. MATERIALS AND METHODS: A comprehensive evaluation of available published
      data included analysis of published full-length papers that were identified with
      Medline and Cancerlit from January 1981 to January 2006. Official proceedings of
      internationally known scientific societies held in the same time period were also
      assessed. RESULTS: Most men with hormone refractory prostate cancer will die of
      their disease in the absence of intercurrent illness, and the various conditions
      arising as a consequence of local and distal cancer progression commonly lead to
      a spectrum of morbidity requiring treatment. Recent data regarding docetaxel
      based chemotherapy have shown small but significant improvements in survival and
      improvement in quality of life in men receiving treatment. However, this therapy
      may not be suitable for all patients. New agents used alone or in combination
      with docetaxel currently are under trial in an attempt to provide much needed
      improvements in outcome. Bone-targeted treatments, particularly late-generation
      bisphosphonates, have added to the range of options, reducing the incidence of
      skeletal complications in some men. Further work is needed to target their use
      more effectively, to explore their efficacy in combination with existing proven
      therapies and to develop new approaches to treat bone metastases. Complications
      arising as a consequence of upper and lower tract dysfunction, haematologic,
      neurologic and psychologic disorders are common. These complications often are
      amenable to effective treatment, but interventions may engender difficult
      clinical and ethical decisions. CONCLUSIONS: Although HRPC is incurable, it is
      not untreatable, and that the clinical management embraces not just chemotherapy,
      but many interventional and supportive therapies. A holistic and supportive
      approach to patient care is vital for optimal management, and is best provided by
      a coordinated, multidisciplinary team including urologists and oncologists.

PMID- 16797119
TI  - A pelvic drain can often be avoided after radical retropubic prostatectomy--an
      update in 552 cases.
AB  - OBJECTIVES: The routine placement of a pelvic drain following radical retropubic
      prostatectomy (RRP) may not be required. We describe our experience in 552
      consecutive RRPs to emphasise the safety of this approach and explain our
      rationale for avoiding a drain when possible. METHODS: RRP was performed in 552
      consecutive patients with clinically localised adenocarcinoma of the prostate
      between January 2002 and June 2005. Clinical and pathologic information was
      documented for each patient. After the prostate was removed and the anastomotic
      sutures tied, the bladder was gently filled with approximately 50 ml of saline
      through the urethral catheter. If there was no leak, a drain was not placed.
      RESULTS: A drain was not placed in 419 (76%) of the 552 patients. We compared the
      postoperative complication rates in those with (D+) and without (D-) a drain.
      There were 27 (5%) immediate postoperative complications and no significant
      difference between the two groups (D+, 6%; D-, 5%; p=0.629): three (1%) patients
      who did not have a drain had a urinoma, one (1%) who had a drain had a
      lymphocele, and two (2%) who had a drain had a small pelvic haematoma.
      CONCLUSIONS: If the bladder neck is preserved or meticulously reconstructed,
      there may be little extravasation and, thus, routine drainage is unnecessary. Our
      4-year experience indicates that morbidity is not increased by omitting a drain
      from the pelvic cavity after RRP in properly selected cases.

PMID- 16797120
TI  - Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway.
AB  - EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been
      shown to suppress cancer cell proliferation, and interfere with the several
      signaling pathways and induce apoptosis. Practically, there is emerging evidence
      that EGCG has a potential to increase the efficacy of chemotherapy in patients.
      We hypothesized that EGCG may exert cell cytotoxicity through modulating AMPK
      (AMP-activated protein kinase) followed by the decrease in COX-2 expression. EGCG
      treatment to colon cancer cells resulted in a strong activation of AMPK and an
      inhibition of COX-2 expression. The decreased COX-2 expression as well as
      prostaglandin E(2) secretion by EGCG was completely abolished by inhibiting AMPK
      by an AMPK inhibitor, Compound C. Also, the activation of AMPK was accompanied
      with the reduction of VEGF (vascular endothelial growth factor) and glucose
      transporter, Glut-1 in EGCG-treated cancer cells. These findings support the
      regulatory role of AMPK in COX-2 expression in EGCG-treated cancer cells.
      Furthermore, we have found that reactive oxygen species (ROS) is an upstream
      signal of AMPK, and the combined treatment of EGCG and chemotherapeutic agents, 5
      FU or Etoposide, exert a novel therapeutic effect on chemo-resistant colon cancer
      cells. AMPK, a molecule of newly defined cancer target, was shown to control COX
      2 in EGCG-treated colon cancer cells.

PMID- 16797121
TI  - Effects of stress and adrenalectomy on activity-regulated cytoskeleton protein
      (Arc) gene expression.
AB  - Activity-regulated cytoskeletal-associated protein (Arc) is an effector immediate
      early gene induced by novelty and involved in consolidation of long-term memory.
      Since activation of glucocorticoid receptors is a prerequisite for memory
      consolidation, we therefore aimed to study the effect of acute restraint stress
      on Arc gene expression in adrenalectomized rats. Acute stress produced a
      significant increase in Arc gene expression in the medial prefrontal cortex, but
      not in the parietal cortex or in the pyramidal cell layer of the hippocampus. The
      basal level of Arc mRNA in adrenalectomized animals was high in the medial
      prefrontal cortex and unaffected by acute stress in these animals. These data are
      consistent with the role of Arc as an integrative modulator of synaptic
      plasticity by emphasizing the potential role of stress and glucocorticoids in the
      control of Arc gene expression.

PMID- 16797122
TI  - Aquaporin-4 knockout regulated cocaine-induced behavior and neurochemical changes
      in mice.
AB  - Aquaporin-4 (AQP4) is the predominant water channel of brain, which mediates
      transmembrane water movement at the blood-brain barrier and at the brain
      cerebrospinal fluid interface. It has been reported that AQP4 deletion results in
      an increase of amino acid and monoamine levels in some brain regions of mice,
      suggesting that AQP4 may participate in region-specific alterations in brain
      amino acid and monoamine metabolism. In the present study, we examined whether
      AQP4 affects neurotransmission in acute and chronic cocaine exposure mice. For
      this purpose, both wild-type and AQP4 knockout mice were used with locomotor
      activity evaluation and microdialysis methods. The results reveal that AQP4
      deletion attenuated locomotor activity in acute and repeated cocaine exposure
      mice, and induced a decrease of extracellular dopamine and glutamate levels in
      the nucleus accumbens (NAc), a brain region known to be critically involved in
      the addictive properties of cocaine. Therefore, AQP4 may play a role in
      regulating extracellular cocaine-induced dopamine and glutamate release in the
      brain reward center, and in turn AQP4 deletion may attenuate cocaine
      reinforcement and dependence.

PMID- 16797123
TI  - Complex interactions between pain and itch.

PMID- 16797124
TI  - Post-operative pain behavior in rats is reduced after single high-concentration
      capsaicin application.
AB  - Surgical procedures associated with tissue injury are often followed by increased
      sensitivity to innocuous and noxious stimuli in the vicinity of the surgical
      wound. The aim of this study was to evaluate the role of transient receptor
      potential vanilloid 1 receptor (TRPV1) containing nociceptors in this process, by
      their functional inactivation using a high-concentration intradermal injection of
      capsaicin in a rat plantar incision model. Paw withdrawal responses to mechanical
      stimuli (von Frey filaments 10-367mN) and to radiant heat applied on plantar skin
      were tested in animals treated with capsaicin or the vehicle 6 days and 24h
      before or 2h after the incision was made. In the vehicle-treated animals,
      mechanical and thermal sensitivity increased significantly 1-96h following the
      incision. Capsaicin applied 24h before the surgery was most effective and
      significantly diminished the development of post-incisional mechanical allodynia
      and hyperalgesia. Thermal hypoalgesia was present in the incised paw after the
      capsaicin treatment. Capsaicin application 6 days before the incision induced
      thermal hypoalgesia before the incision but did not prevent completely the
      thermal hyperalgesia after the incision, while there was also a reduction of
      mechanical hypersensitivity. Application of the capsaicin injection after the
      incision showed its first effect at 2h after the injection and at 24h the effect
      was comparable with the 6 days pretreatment. Our results show an important role
      of TRPV1-containing nociceptors in the development of post-surgical
      hypersensitivity and suggest that local, high-concentration capsaicin treatment
      could be used to reduce it.

PMID- 16797125
TI  - Differential association of general and health self-efficacy with disability,
      health-related quality of life and psychological distress from musculoskeletal
      pain in a cross-sectional general adult population survey.
AB  - Although evidence reveals that self-efficacy is associated with disability in
      people with pain, there is less known about this relationship in primary care
      settings and no published information in general population samples. This study
      aimed to assess the relationship between pain, self-efficacy, health-related
      quality of life, psychological distress and disability in a general population
      sample. A randomly selected sample from electoral registers of the lower North
      Island of New Zealand was mailed a survey questionnaire. Presence of
      musculoskeletal pain was defined as "pain present for at least seven consecutive
      days during the last month". Respondents were divided into three groups on the
      basis of pain: no pain, pain present for less than 12 months and pain present for
      12 months or longer. Health Self-efficacy, General Self-efficacy, General Health
      Questionnaire, modified Health Assessment Questionnaire and EuroQol-5D were also
      included in the survey instrument. There were 289/471 (61%) returned
      questionnaires from eligible subjects (of an original sample of 540). General
      linear modelling found evidence of an association between pain status and self
      efficacy with disability, explaining 16.4-18.8% of variability in mHAQ scores. In
      addition, we found evidence of an interaction between pain status and general
      self-efficacy, suggesting a stronger relationship between general self-efficacy
      and disability for pain present for 12 months or more. This interaction was not
      observed for health self-efficacy. General self-efficacy was more strongly
      related to psychological distress and this association was not influenced by pain
      status. Health-related quality of life was associated with health self-efficacy
      but not general self-efficacy.

PMID- 16797126
TI  - Prevalence of Cryptosporidium and Giardia in free-ranging wild cervids in Norway.
AB  - Faecal samples were collected from 1,190 wild cervids in Norway and analyzed for
      cysts/oocysts of the protozoan parasites Giardia and Cryptosporidium. Samples
      were from calves, yearlings and adults of moose (Alces alces), red deer (Cervus
      elaphus), roe deer (Capreolus capreolus) and reindeer (Rangifer tarandus) shot
      during the hunting season. Cryptosporidium was found in 15 (3.3%) of 455 moose, 1
      (0.3%) of 289 red deer, 18 (6.2%) of 291 roe deer, but was not found in any of
      155 reindeer. Giardia was found in 56 (12.3%) moose, 5 (1.7%) red deer, 45
      (15.5%) roe deer and 11 (7.1%) reindeer. The calves had the highest prevalence of
      infection, but this was only statistically significant for Giardia in moose and
      for Cryptosporidium and Giardia in roe deer. Calves generally had the highest
      intensity of infection, but this difference was only statistically significant
      for calves with Giarda and the highest intensity of infection. Both Giardia and
      Cryptosporidium were found in samples from several geographical areas, indicating
      that these parasites are distributed among the cervid population in all parts of
      Norway, especially in moose and roe deer. This is the first published report of
      Cryptosporidium in moose and of Giardia in reindeer.

PMID- 16797127
TI  - Septicemia as a cause of death in burns: an autopsy study.
AB  - In burn victims, invasion by the bacteria is not unexpected, despite advances in
      antibiotics, and it has been reported that in the absence of topical therapy, the
      superficial areas of burn wound contain up to 100 million organisms per gram of
      tissue within 48h following the injury. We examined the autopsy reports of 334
      cases who died because of complicated burns and who underwent medico-legal
      autopsy during a period of 5 years to study the rate of infection/sepsis. It was
      observed that in 65% of fatal burn cases, septicemia was the cause of death.
      Pseudomonas aeuroginosa and Klebsiella sp. were the most common organism,
      isolated either singly or in combination in 29% and 28% cases, respectively. High
      mortality from burns in young married women has been recognized as an alarming
      and contentious problem in India, particularly among the low socio-economic
      groups. We found that the females aged 21-25 were the most common victims
      accounting for 37% of burn fatalities due to septicemia. It was concluded that to
      carry out periodic review of patterns of isolation and susceptibility profiles of
      microorganisms infecting burn wounds should be a routine in all burn units. In
      view of the limited resources of developing countries, we recommend the use of
      available scoring systems to estimate burn outcome so that the best care can be
      directed to those who have a better chance of improvement.

PMID- 16797128
TI  - Regional and cellular distribution of the extracellular matrix protein tenascin-C
      in the chick forebrain and its role in neonatal learning.
AB  - The juvenile brain's pronounced synaptic plasticity in response to early
      experience and learning events is related to the fact that the genetically pre
      programmed molecular machinery mediating neuronal development and synapse
      formation, is activated throughout postnatal brain development and thereby can be
      recruited for learning and long-term memory formation. In situ hybridization and
      immunocytochemistry experiments revealed that tenascin-C, one candidate molecule
      which we suspect to be involved in neonatal learning, is expressed in the
      forebrain of domestic chicks around the sensitive period during which auditory
      filial imprinting takes place. The involvement of tenascin-C in this juvenile
      learning task was tested by injections of monoclonal antibodies directed to
      distinct domains of the tenascin-C molecule into the avian prefrontal cortex
      analog, the medio-rostral nidopallium/mesopallium (formerly termed medio-rostral
      neostriatum/hyperstriatum ventrale), a forebrain area which has been shown to be
      critically involved in auditory filial imprinting. Injections of monoclonal
      antibody Tn 68, which is directed against a cell-binding domain of the tenascin-C
      molecule, strongly reduced the imprinting rate, as opposed to injections of the
      monoclonal antibody Tn 578, which binds to a domain involved in neurite
      outgrowth. Double labeling immunohistochemistry revealed that tenascin-C is
      associated with neurons which express the Ca(2+)-binding protein parvalbumin, and
      displays a staining pattern highly reminiscent of perineuronal nets of the
      extracellular matrix. These results indicate that a distinct domain of tenascin-C
      is functionally involved in the juvenile learning process of filial imprinting
      and further suggest a critical role of a specific neuronal subpopulation.

PMID- 16797129
TI  - Reversible inactivation of the dorsal hippocampus by tetrodotoxin or lidocaine: a
      comparative study on cerebral functional activity and motor coordination in the
      rat.
AB  - Reversible inactivation of the hippocampus by lidocaine or tetrodotoxin is used
      to investigate implications of this structure in memory processes. Crucial points
      related to such inactivation are the temporal and spatial extents of the
      blockade. We compared effects of intrahippocampal infusions of commonly-used
      doses of lidocaine (5 or 10 mug) or tetrodotoxin (5 or 10 ng) in rats at two post
      infusion delays (5 or 30 min), using 2-deoxyglucose autoradiography to visualize
      local cerebral glucose metabolism, and beam-walking performance to assess motor
      coordination. In addition, memory retrieval was evaluated in a water maze after
      bilateral infusions of 10 mug lidocaine. A unilateral tetrodotoxin infusion
      induced dose- and time-dependent reductions of 2-deoxyglucose uptake in the
      vicinity of the infusion site (dorsal hippocampus: -29% to -67%) and in other
      ipsi- and contralateral brain regions (ventral hippocampus, lateral thalamus,
      cortical regions). The maximal effect was at 10 ng, at the delay of 30 min
      between the tetrodotoxin infusion and the 2-deoxyglucose injection. Uni- and
      bilateral infusions of tetrodotoxin induced dramatic motor coordination deficits.
      Conversely, lidocaine reduced 2-deoxyglucose uptake (-19%) in the dorsal
      hippocampus only at 10 mug, with weak extrahippocampal effects. Whether infused
      uni- or bilaterally and regardless of the dose, lidocaine did not alter motor
      coordination. When infused bilaterally, however, 10 microg of lidocaine impaired
      short-term retrieval of spatial information in a water maze. Because lidocaine i)
      induced a weak though significant functional blockade mainly restricted to the
      infusion site, ii) had no consequences on motor coordination and, nevertheless
      iii) altered short-term spatial memory retrieval, we conclude that acute
      intrahippocampal infusions of lidocaine may offer some advantages over
      tetrodotoxin at the doses used herein.

PMID- 16797130
TI  - Differential effects of prenatal stress on the morphological maturation of
      hippocampal neurons.
AB  - The present study was designed to clarify an intensity-dependent effect of
      prenatal stress on the morphological development of hippocampal neurons in rats.
      In addition, the involvement of receptors for glucocorticoids, i.e.
      mineralocorticoid receptors and glucocorticoid receptors, in stress-induced
      changes in the morphology of hippocampal neurons was examined by an in vitro
      pharmacological approach. The effects of mild prenatal stress on neurogenesis and
      long-term potentiation in the hippocampus were also investigated in adult
      offspring. Prenatal stress affected the morphological development of the
      hippocampus in an intensity-dependent manner. Short-lasting, mild prenatal stress
      enhanced neonatal neurogenesis and differentiation of processes of hippocampal
      neurons, whereas long-lasting, severe stress impaired their morphology.
      Mineralocorticoid receptor was found to mediate enhancement of neurogenesis and
      differentiation of processes of cultured hippocampal neurons. In contrast,
      glucocorticoid receptor was involved in the suppression of their morphology.
      Short-lasting, mild prenatal stress, which has previously been shown to enhance
      learning performance in adult offspring, facilitated neurogenesis and long-term
      potentiation in the adult hippocampus. These findings suggest that prenatal
      stress has enhancing and suppressing effects on the development of hippocampal
      neurons depending on intensity, and that mineralocorticoid receptors and
      glucocorticoid receptors contribute to stress-induced morphological changes.

PMID- 16797131
TI  - Cellular and subcellular localization of alpha-1 adrenoceptors in the rat visual
      cortex.
AB  - Noradrenaline is thought to play modulatory roles in a number of physiological,
      behavioral, and cellular processes. Although many of these modulatory effects are
      mediated through alpha-1 adrenoceptors, basic knowledge of the cellular and
      subcellular distributions of these receptors is limited. We investigated the
      laminar distribution pattern of alpha-1 adrenoceptors in rat visual cortex, using
      immunohistochemistry at both light and electron microscopic levels. Affinity
      purified anti-alpha-1 antibody was confirmed to react only with a single band of
      about 70-80 kDa in total proteins prepared from rat visual cortex. Alpha-1
      adrenoceptors were widely distributed though all cortical layers, but relatively
      high in density in layers I, II/III, and V. Immunoreactivity was observed in both
      neuronal perikarya and processes including apical dendrites. In double-labeling
      experiments with anti-microtubule-associated protein 2, anti-neurofilament, anti
      glial fibrillary acidic protein, anti-glutamic acid decarboxylase 65/67, anti-2-3
      cyclic nucleotide 3-phosphodiesterase, and anti-tyrosine hydroxylase antibodies,
      alpha-1 adrenoceptors were found mainly in dendrites and somata of microtubule
      associated protein 2-immunopositive neurons. About 20% of alpha-1 adrenoceptors
      were in GABAergic neurons. A small number of alpha-1 adrenoceptors were also
      distributed in axons of excitatory neurons, astrocytes, oligodendrocytes and
      noradrenergic fibers. Using an immunoelectron microscopic technique, numerous
      regions of alpha-1 adrenoceptor immunoreactivity were found in cell somata, on
      membranes of dendrites, and in postsynaptic regions. Moreover, a small number of
      immunoreaction products were also detected in axons and presynaptic sites. These
      findings provide the first quantitative evidence regarding the cellular and
      subcellular localization of alpha-1 adrenoceptor immunoreactivity in visual
      cortex. Moreover, the ultrastructural distribution of alpha-1 adrenoceptor
      immunoreactivity suggests that alpha-1 adrenoceptors are transported mainly into
      dendrites and that they exert effects at postsynaptic sites of neurons.

PMID- 16797132
TI  - Immunohistochemical and western analyses of protein arginine N-methyltransferase
      3 in the mouse brain.
AB  - The distribution of protein arginine N-methyltransferase 3 (PRMT3) was
      investigated in the mouse brain using indirect immunofluorescence. PRMT3 was
      observed to be localized in the cell bodies and dendrites of neurons but not in
      the axons and glial cells, indicating that PRMT3 is involved in neuronal
      function. The distribution of the immunoreactive neurons in the brain was uneven,
      indicating that PRMT3 plays a role in specific neuronal systems such as the motor
      and limbic systems, as well as functions related to the cerebellum. The present
      ontogenetic analysis of PRMT1 and PRMT3 using Western blot methodology clearly
      revealed that PRMT3 develops during the perinatal stage and its expression is
      maintained even in adulthood. PRMT1, on the other hand, is expressed transiently
      during the early embryonic stage. These findings indicate that PRMT3 is related
      with neuronal function in both young and adult brains, while PRMT1 has roles in
      the immature brain, such as the formation of neural circuits.

PMID- 16797133
TI  - Topography of spinal neurons active during hindlimb withdrawal reflexes in the
      decerebrate cat.
AB  - There exists a spatial organization of receptive fields and a modular
      organization of the flexion withdrawal reflex system. However, the three
      dimensional location and organization of interneurons interposed in flexion
      reflex pathways has not been systematically examined. We determined the
      anatomical locations of spinal neurons involved in the hindlimb flexion
      withdrawal reflex using expression of the immediate early gene c-fos and the
      corresponding FOS protein. The flexion withdrawal reflex was evoked in
      decerebrate cats via stimulation of the tibial or superficial peroneal nerve.
      Animals that received stimulation had significantly larger numbers of cells
      expressing FOS-like immunoreactivity (42.7+/-2.3 cells/section, mean+/-standard
      error of the mean) than operated unstimulated controls (18.6+/-1.4
      cells/section). Compared with controls, cells expressing FOS-like
      immunoreactivity were located predominantly on the ipsilateral side, in laminae
      IV-VI, at L6 and rostral L7 segments, and between 20% and 60% of the distance
      from the midline to the lateral border of the ventral gray matter. Labeled
      neurons resulting from tibial nerve stimulation were medial to neurons labeled
      following superficial peroneal nerve stimulation in laminae I-VI, but not VII.
      The mean mediolateral positions of labeled neurons from both nerves shifted
      medially as the transverse plane in which they were viewed was moved from rostral
      to caudal and as the coronal plane in which they were viewed was moved from
      dorsal to ventral. The mediolateral separation between populations of labeled
      cells was consistent with primary afferent projections and the location of reflex
      encoders. This topographical segregation corresponding to different afferent
      inputs is a possible anatomical substrate for a modular organization of the
      flexion withdrawal reflex system.

PMID- 16797134
TI  - Increased density and synapto-protective effect of adenosine A2A receptors upon
      sub-chronic restraint stress.
AB  - Stress initially causes adaptive changes in the brain and can lead to
      neurodegeneration if continuously present. Noxious brain conditions trigger the
      release of adenosine that can control brain function and neurodegeneration
      through inhibitory A(1) and facilitatory A(2A) receptors. We tested the effect of
      restraint stress on the density of adenosine receptors and their effect on the
      outcome of stress, focusing in a known affected region, the hippocampus. Sub
      chronic restraint stress (6 h/day for 7 days) caused a parallel decrease of the
      density of A(1) receptors (15-20%) and an increase (near 250%) of A(2A) receptor
      density in rat hippocampal nerve terminals. This indicates that sub-chronic
      stress unbalances adenosine receptors, up-regulating A(2A) and down-regulating
      A(1) receptors. Sub-chronic stress did not cause hippocampal neurodegeneration
      but decreased the immunoreactivity (immunohistochemistry and Western blot) of a
      synaptic marker, synaptophysin. The blockade of A(2A) receptors with 7-(2
      phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
      (0.05 mg/kg, daily i.p. injection) attenuated the loss of synaptophysin
      immunoreactivity observed in the hippocampus of rats subjected to sub-chronic
      restraint stress. This ability of A(2A) receptor antagonists to prevent the
      earliest stress-induced synaptic modifications provides a neurochemical and
      morphological correlate for the interest of A(2A) receptor antagonists to
      attenuate the burden of chronic stress.

PMID- 16797135
TI  - Dense core vesicles resemble active-zone transport vesicles and are diminished
      following synaptogenesis in mature hippocampal slices.
AB  - Large dense core vesicles (approximately 100 nm) contain neuroactive peptides and
      other co-transmitters. Smaller dense core vesicles (approximately 80 nm) are
      known to contain components of the presynaptic active zone and thought to
      transport and deliver these components during developmental synaptogenesis. It is
      not known whether excitatory axons in area CA1 contain such dense core vesicles,
      and whether they contribute to synaptic plasticity of mature hippocampus. Serial
      section electron microscopy was used to identify dense core vesicles in
      presynaptic axons in s. radiatum of area CA1 in adult rat hippocampus.
      Comparisons were made among perfusion-fixed hippocampus and hippocampal slices
      that undergo synaptogenesis during recovery in vitro. Dense core vesicles
      occurred in 26.1+/-3.6% of axonal boutons in perfusion fixed hippocampus, and in
      only 17.6+/-4.5% of axonal boutons in hippocampal slices (P<0.01). Most of the
      dense core vesicle positive boutons contained only one dense core vesicle, and no
      reconstructed axonal bouton had more than a total of 10 dense core vesicles in
      either condition. Overall the dense core vesicles had average diameters of 79+/
      11 nm. These small dense core vesicles were usually located near nonsynaptic
      membranes and rarely occurred near the edge of a presynaptic active zone. Their
      size, low frequency, locations, and decrease following recuperative
      synaptogenesis in slices are novel findings that merit further study with respect
      to small dense core vesicle content and possible contributions to synapse
      assembly and plasticity in the mature hippocampus.

PMID- 16797136
TI  - Dendritic architecture of the von Economo neurons.
AB  - The von Economo neurons are one of the few known specializations to hominoid
      cortical microcircuitry. Here, using a Golgi preparation of a human postmortem
      brain, we describe the dendritic architecture of this unique population of
      neurons. We have found that, in contrast to layer 5 pyramidal neurons, the von
      Economo neurons have sparse dendritic trees and symmetric apical and basal
      components. This result provides the first detailed anatomical description of a
      neuron type unique to great apes and humans.

PMID- 16797137
TI  - Development of GABA-sensitive spasticity and rigidity in rats after transient
      spinal cord ischemia: a qualitative and quantitative electrophysiological and
      histopathological study.
AB  - Transient spinal cord ischemia may lead to a progressive degeneration of spinal
      interneurons and subsequently to increased hind limb motor tone. In the present
      work we sought to characterize the rigidity and spasticity components of this
      altered motor function by: i) tonic electromyographic activity measured in
      gastrocnemius muscle before and after ischemia, ii) measurement of muscle
      resistance during the period of ankle flexion and corresponding changes in
      electromyographic activity, iii) changes in Hoffmann reflex, and, iv) motor
      evoked potentials. In addition the effect of intrathecal treatment with baclofen
      (GABAB receptor agonist; 1 microg), nipecotic acid (GABA uptake inhibitor; 300
      microg) and dorsal L2-L5 rhizotomy on spasticity and rigidity was studied.
      Finally, the changes in spinal choline acetyltransferase (ChAT) and vesicular
      glutamate transporter 2 and 1 (VGLUT2 and VGLUT1) expression were characterized
      using immunofluorescence and confocal microscopy. At 3-7 days after ischemia an
      increase in tonic electromyographic activity with a variable degree of rigidity
      was seen. In animals with modest rigidity a velocity-dependent increase in muscle
      resistance and corresponding appearance in electromyographic activity (consistent
      with the presence of spasticity) was measured during ankle rotation (4-612
      degrees /s rotation). Measurement of the H-reflex revealed a significant increase
      in Hmax/Mmax ratio and a significant loss of rate-dependent inhibition. In the
      same animals a potent increase in motor evoked potential amplitudes was measured
      and this change correlated positively with the increased H-reflex responses.
      Spasticity and rigidity were consistently present for a minimum of 3 months after
      ischemia. Intrathecal treatment with baclofen (GABA B receptor agonist) and
      nipecotic acid (GABA uptake inhibitor) provided a significant suppression of
      spasticity, rigidity, H-reflex or motor evoked potentials. Dorsal L2-L5 rhizotomy
      significantly decreased muscle resistance but had no effect on increased
      amplitudes of motor evoked potentials. Confocal analysis of spinal cord sections
      at 8 weeks-12 months after ischemia revealed a continuing presence of ChAT
      positive alpha-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals
      but a selective loss of small presumably inhibitory interneurons between laminae
      V-VII. These data demonstrate that brief transient spinal cord ischemia in rat
      leads to a consistent development of spasticity and rigidity. The lack of
      significant suppressive effect of dorsal L2-L5 rhizotomy on motor evoked
      potentials response indicates that descending motor input into alpha-motoneurons
      is independent on Ia afferent couplings and can independently contribute to
      increased alpha-motoneuronal excitability. The pharmacology of this effect
      emphasizes the potent role of GABAergic type B receptors in regulating both the
      spasticity and rigidity.

PMID- 16797138
TI  - Degeneration of dopaminergic mesocortical neurons and activation of compensatory
      processes induced by a long-term paraquat administration in rats: implications
      for Parkinson's disease.
AB  - A deficiency of the dopaminergic transmission in the mesocortical system has been
      suggested to contribute to cognitive disturbances in Parkinson's disease.
      Therefore, the aim of the present study was to examine whether the long-term
      administration of a commonly used herbicide, paraquat, which has already been
      found to induce a slowly progressing degeneration of the nigrostriatal neurons,
      influences mesocortical dopaminergic neurons in rats. Paraquat at a dose of 10
      mg/kg i.p. was injected either acutely or once a week for 4, 8, 12 and 24 weeks.
      Acute treatment with this pesticide increased the level of homovanillic acid
      (HVA) and HVA/dopamine ratio in the prefrontal cortex. After 8 weeks of
      administration paraquat increased the number of stereologically counted tyrosine
      hydroxylase-immunoreactive (TH-ir) neurons and their staining intensity in the
      ventral tegmental area (VTA), which is a source of the mesocortical dopaminergic
      projection. At the same time, few TH-ir neurons appeared in different regions of
      the cerebral cortex: in the frontal, cingulate, retrosplenial and parietal
      cortices. Chronic paraquat administration did not influence the level of dopamine
      in the prefrontal cortex but increased the levels of its metabolites: 3,4
      dihydroxyphenylacetic acid (after 8-12 weeks), HVA (after 4 and 12 weeks) and
      HVA/dopamine ratio (4 weeks). After 24 weeks this pesticide reduced the number of
      TH-ir neurons in the VTA by 42% and of the Nissl-stained neurons by 26%, and
      induced shrinkage of this structure by ca. 25%. Moreover, TH-ir neurons in the
      cortex were no more visible after such a long period of administration and levels
      of dopamine metabolites returned to control values. The present results suggest
      that the long-term paraquat administration destroys dopaminergic neurons of the
      VTA. However, compensatory activation of the VTA neurons and cortex overcomes
      progressing degeneration and maintains cortical dopaminergic transmission.

PMID- 16797139
TI  - Reasons for substance use and vulnerability factors in patients with substance
      use disorder and anxiety or mood disorders.
AB  - This cross-sectional study examined the reasons for substance use and the
      presence of vulnerability factors such as substance sensitivity, sensation
      seeking, and symptoms related to the attention deficit hyperactivity disorder
      (ADHD) in patients with substance use disorder (SUD) and comorbid mood and
      anxiety disorders by using the Structured Clinical Interview for the Spectrum of
      Substance Use (SCI-SUBS), a novel instrument designed to explore the spectrum of
      substance use and its clinical correlates. Study participants included 61
      patients with SUD and mood or anxiety disorder, and two comparison groups
      including 35 patients with SUD only and 50 controls not in treatment for mental
      disorders or SUD. We found that patients with co-morbid mood or anxiety disorder
      had significantly higher scores on the SCI-SUBS domains 'substance sensitivity'
      and 'self-medication' as compared to those with SUD only. Scores on 'sensation
      seeking' and 'ADHD' domains were similar between both groups of patients and
      higher than in controls. Patients with comorbid mood or anxiety disorders showed
      a higher sensitivity to substances and were more prone to self-medication than
      those with SUD only. These characteristics should be taken into account in the
      diagnostic assessment and in long-term treatment to decrease the risk of relapse.

PMID- 16797140
TI  - Sulfur-containing iridoid glucosides from Paederia scandens.
AB  - A new sulfur-containing iridoid glucoside, named paederoside B, was isolated from
      the stems of Paederia scandens. The structure of the new compound was elucidated
      as paederosidyl paederosidate by spectral evidence.

PMID- 16797141
TI  - Sesquiterpenoids and phenolics from roots of Cichorium endivia var. crispum.
AB  - Twelve known sesquiterpene lactones and the new guaianolide 10beta-methoxy
      1alpha, 11beta,13-tetrahydrolactucin (10), together with three known phenolic
      acid esters were isolated from roots of Cichorium endivia var. crispum. The
      compounds were characterized by spectral methods.

PMID- 16797142
TI  - Preliminary antiproliferative effects of some species of Terminalia, Combretum
      and Pteleopsis collected in Tanzania on some human cancer cell lines.
AB  - Methanolic extracts (25 microug/ml) of species belonging to the genera of
      Combretum, Terminalia and Pteleopsis, collected during a field expedition in
      Tanzania in 1999, were screened for their antiproliferative and cytotoxic effects
      against three human cancer cell lines (HeLa, cervical carcinoma; T 24, bladder
      carcinoma; and MCF 7, breast carcinoma). A leaf extract of Combretum fragrans and
      a fruit extract of C. zeyheri gave the strongest antiproliferative and cytotoxic
      effects of all the twenty-four extracts screened in this investigation. In
      contrast to the highly powerful leaf extract of C. fragrans, the root extract of
      this species gave no cytotoxic effects against the investigated cancer cell lines
      at a concentration of 25 microg/ml. The other investigated species of Combretum
      and Terminalia differed greatly in their cytotoxic potential. Root extracts of
      Terminalia sambesiaca and T. sericea gave the strongest cytotoxic effects of the
      five species of Terminalia used in this study. Eight of the twenty-four
      investigated plant extracts showed pronounced cytotoxic effects (<30%
      proliferation compared to the control) against the T 24 bladder cancer cells,
      seven against the HeLa cells and four against the MCF 7 cells.

PMID- 16797143
TI  - Evaluation of cytotoxic activities of some medicinal polypore fungi from China.
AB  - The petrol ether, ethyl acetate and methanol extracts of eight medicinal polypore
      fungi from China were evaluated for cytotoxic activities using MTT-dye assay. All
      the petrol ether and ethyl acetate extracts exhibited cytotoxicity against human
      cervix epitheloid carcinoma cell lines (Hela) and human hepatoma cell lines (SMMC
      7721). Cytotoxicity activity was also observed in the methanol extracts of
      Phellinus conchatus and Pycnoporus sanquineus, but the methanol extracts from
      Cryptoporus volvatus, Fomitopsis pinicola, Fomes hornodermus, Lenzites betulina,
      Trametes gibbosa and Trametes orientalis showed weak activity when compared with
      quercetin.

PMID- 16797144
TI  - Antimicrobial activity of coupled hydroxyanthracenones isolated from plants of
      the genus Karwinskia.
AB  - The in vitro activity of some isolated hydroxyanthracenones belonging to the
      genus Karwinskia against four bacteria, six filamentous fungi and four yeast are
      reported. These hydroxyanthracenones were found to possess antimicrobial
      activity, particularly against Streptococcus pyogenes, Candida albicans, C.
      boidinii, C. glabrata and Cryptococcus neoformans; minimal inhibitory
      concentrations range between 16 and 2 microg/ml.

PMID- 16797145
TI  - Free radical scavenging activity of different extracts and some constituents from
      the leaves of Ligustrum vulgare and L. delavayanum.
AB  - The free radical scavenging activity of the water infusions, different organic
      solvent extracts and some constituents from Ligustrum vulgare and Ligustrum
      delavayanum leaves was assessed with the aid of DPPH radical. Among the samples
      screened, water infusions had the strongest free radical scavenging capacity.
      From the tested compounds scavenging active flavonoid aglycones are present in
      the most active chloroform fractions from both leaves samples.

PMID- 16797146
TI  - Antioxidant activity of medicinal plant polysaccharides.
AB  - Eleven polysaccharides have been isolated from the leaves of Arctium lappa var.
      herkules, Aloe barbadensis, Althaea officinalis var. robusta, Plantago lanceolata
      var. libor, aerial parts and roots of Rudbeckia fulgida var. sullivantii, stems
      of Mahonia aquifolium, and peach-tree (Prunus persica) gum exudates. The
      polysaccharides were investigated for their ability to inhibit peroxidation of
      soyabean lecithin liposomes by OH radicals. The highest inhibition was found with
      glucuronoxylans of A. officinalis var. robusta and P. lanceolata var. libor,
      aerial parts. Their antioxidant activity accounted for approximately 69% of the
      activity of the reference compound alpha-tocopherol. The activity of eight
      polysaccharides ranged from 20 to 45%, while the fructofuranan from P. lanceolata
      var. libor roots was practically inactive.

PMID- 16797147
TI  - The argRB of Escherichia coli is rare in isolates obtained from natural sources.
AB  - A single nucleotide polymorphism between Escherichia coli strains K12 and B is
      known to alter the mechanism by which the arginine repressor regulates arginine
      biosynthesis, from a regulated system in E. coli K12 to a deregulated system in
      E. coli B. Laboratory experiments have demonstrated that the different regulatory
      strategies are selectively favored under different environmental conditions. In
      this study we analyzed 537 E. coli strains and show that the argR allele in E.
      coli B, which causes deregulation, is rare in isolates obtained from natural
      sources. Moreover, sequence analysis of 85 strains shows no evidence of selection
      at the arginine repressor locus. This illustrates that analysis of sequence data
      is insufficient to detect selection of uncommon alleles in rare environments.

PMID- 16797148
TI  - Physicians' views and practices concerning menopausal hormone therapy.
AB  - OBJECTIVE: To examine physicians' views and practices concerning
      estrogen+progestogen therapy (EPT). DESIGN: Questionnaires were mailed to a
      random sample of physicians in the United States (US) in 2003. A total of 1614
      (53.8%) surveys were returned (633 obstetricians and gynecologists (Ob/Gyns), 571
      family practitioners, and 410 internists). RESULTS: Only a minority of the
      physicians (16%) would offer EPT to menopausal women in the absence of menopausal
      symptoms (26% Ob/Gyn, 11% family practitioners, 6% internists, p<0.0001).
      However, many physicians (62%) believed that EPT could be offered "short term" to
      menopausal women with menopausal symptoms assuming no contraindications (82%
      Ob/Gyn, 54% family practitioners, 42% internists; p<0.0001). Irrespective of
      specialty, the strongest contraindications to EPT use reported by these
      physicians were personal history of breast cancer (93%), thrombosis (92%),
      cerebrovascular disease (84%), ischemic heart disease (74%), uterine cancer
      (73%), as well as women's subjective "concern" about breast cancer (57%).
      Procedures reported as always required by physicians for continuing women on EPT
      were breast examination (97%), mammogram (96%), blood pressure measurement (94%),
      and pelvic examination (91%). CONCLUSIONS: Internists and family practitioners
      address more contraindications to EPT use than Ob-Gyns. Although many physicians
      appear to be accepting of short-term use of EPT for menopausal indications in the
      absence of contraindications, the majority would not prescribe it for
      prophylactic purposes.

PMID- 16797149
TI  - Knowledge of osteoporosis correlated with hormone therapy use and health status.
AB  - OBJECTIVES: The study objectives were: (a) to evaluate knowledge about
      osteoporosis and to identify its correlates among women > or =40 years of age
      attending outpatient centers; (b) to compare the level of knowledge between women
      already receiving treatment for osteoporosis and first-time attendees. METHODS: A
      cross-sectional survey was conducted with women recruited from nine outpatient
      centres in the Czech Republic. The women were divided into two subgroups:
      patients who have already been diagnosed with osteoporosis (osteopenia) and who
      are receiving treatment for the disease (OS group); first-time attendees who have
      been referred for the assessment of osteoporosis (comparison group). The
      patient's knowledge of osteoporosis was assessed using the Osteoporosis
      Questionnaire (OPQ) developed by Pande et al. [Pande KC, Takats D, Kanis JA,
      Edwards V, Slade P, McCloskey EV. Development of a questionnaire (OPQ) to assess
      patient's knowledge about osteoporosis. Maturitas 2000;37:75-81]. RESULTS: A
      total of 474 women (median age 63 years) were studied (306 in the OS group, 168
      in the comparison group). Knowledge scores based on OPQ (median) were 7 and 6
      points in the OS and comparison groups, respectively. When adjusted for age, the
      statistics showed better knowledge patients in the OS group (P=0.019). In both
      the OS and comparison groups, knowledge was found to be correlated positively
      with education (P<0.001) and experience of hormone replacement therapy (HRT)
      (P<0.001) and negatively with age (P<0.001). Knowledge was higher among women
      with better health status in the OS group. CONCLUSION: Knowledge about
      osteoporosis among Czech women aged > or =40 years and attending outpatient
      centers is relatively poor. To improve it, special attention should be paid to
      elderly women, those who have not used HRT, poorly educated women and those
      treated with several drugs.

PMID- 16797150
TI  - Drug/lactose co-micronization by jet milling to improve aerosolization properties
      of a powder for inhalation.
AB  - The aim of this work was to formulate a powder for inhalation with fusafungine, a
      drug substance initially highly cohesive. The classical approach based on
      micronization by jet milling to prepare respirable drug particles and then
      blending with a carrier was first applied. A fractional factorial experimental
      design was implemented to screen six formulation parameters. The effect of
      drug/lactose co-micronization on aerosolization was then evaluated. In vitro
      deposition studies were performed with the twin stage glass impinger and the
      inhaler Spinhaler. Micronization did not induce DSC-detectable amorphization and
      gave a highly cohesive, poor flowable powder with a theoretical aerodynamic
      diameter of 5 microm. The powder was then blended with coarse lactose and
      optionally fine lactose. Unfortunately, the respirable fraction could not be
      optimized and remained below 10%. On the other hand, a co-micronized powder
      drug/fine lactose 50:50 gave a respirable fraction of 16%. Following blending
      with a carrier, the respirable fraction and the emitted dose fraction reached 23%
      and 69%, respectively. The use of a fine lactose grade for co-micronization was
      essential. In conclusion, this study demonstrated that co-micronization with a
      fine lactose is an efficient and simple strategy to formulate a powder for
      inhalation with enhanced aerosolization properties, especially for highly
      cohesive drug substance.

PMID- 16797151
TI  - Anti-inflammatory, anti-nociceptive and antipyretic effects of extracts of
      Phrygilanthus acutifolius flowers.
AB  - This study was intended to evaluate the anti-inflammatory, antipyretic and
      analgesic activities of aqueous and ethanol extracts of Phrygilanthus acutifolius
      flowers in several experimental standard models in rats, following oral
      administration. The results showed that the aqueous extract significantly reduced
      the oedema induced by carrageenan within 1-5 h post-dosing at all dose levels
      used. On the analgesia property, acetic acid-induced writhing was significantly
      reduced. In the formalin test, the extract also significantly decreased the
      painful stimulus in both phases of the test. The tail immersion confirms central
      acting analgesic property of the extracts. Overall, the analgesic tests conducted
      revealed that the extract had central and peripheral properties. Its effects on
      pyresis were also appreciable. It significantly reduced fever at doses greater
      than 200 mg/kg within 2 h on yeast-induced hyperthermia in rats.

PMID- 16797152
TI  - Succession pattern of carrion-feeding insects in Paramo, Colombia.
AB  - The minimum postmortem interval can be estimated based on knowledge of the
      pattern of insect succession on a corpse. To use this approach requires that we
      take into account the rates of insect development associated with particular
      climatological conditions of the region. This study is the first to look at
      insect succession on decomposing carcasses in the high altitude plains (Paramo)
      in Colombia, at 3035 m above sea level. Five stages of decomposition were
      designated with indicator species identified for each stage: Calliphora
      nigribasis at the fresh stage; Compsomyiops verena at the bloated stage;
      Compsomyiops boliviana during active decay; Stearibia nigriceps and Hydrotaea sp.
      during advanced decay and Leptocera sp. for dry remains. A succession table is
      presented for carrion-associated species of the region, which can be used for
      estimating time since death in similar areas. Compsomyiops boliviana is reported
      for the first time in Colombia.

PMID- 16797153
TI  - Future in forensic medicine as an academic discipline--focussing on research.
AB  - Based on a short description of the areas of operation and competence of forensic
      medicine, current problems, structural deficits of the speciality and possible
      solutions are discussed. To give future to legal medicine as an academic
      discipline, research must be given priority over routine casework.

PMID- 16797154
TI  - Effects of estradiol on gonadotrophin release, estrus and ovulation in CIDR
      treated beef cattle.
AB  - The effects of estradiol-17beta (E-17beta) or estradiol benzoate (EB) on
      gonadotrophin release, estrus and ovulation in beef cattle were evaluated in two
      experiments. In experiment 1, 16 ovariectomized cows received a previously used
      CIDR insert from days 0 to 7 and 1mg of EB on day 8; they also received 5mg of E
      17beta on days 0 or 1, or 5mg of E-17beta+100mg of progesterone on day 0. There
      was only an effect of time (P<0.0001) on plasma concentrations of progesterone,
      estradiol, FSH, and LH. Following treatment with E-17beta, plasma FSH
      concentrations were suppressed for approximately 36 h, whereas plasma LH
      concentrations were reduced (P<0.05) for 6 h, but surged within 24 h. Injecting
      1mg of EB 24 h after CIDR removal decreased (P<0.02) plasma LH concentrations for
      6h, followed by an LH surge at 18 h. In experiment 2, ovary-intact heifers (n=40)
      received a used CIDR and 5mg of E-17beta+100mg of progesterone on day 0. On day
      7, CIDR were removed, PGF given, and heifers received nothing (control) or 1mg of
      EB 12, 24, or 36 h later. In these groups, plasma LH peaked (mean+/-SEM) 78.0+/
      23.0, 37.8+/-8.5, 44.4+/-10.3, and 51.0+/-5.1 h after CIDR removal (means,
      P<0.001; variances, P<0.001) and intervals from CIDR removal to ovulation were
      102.0+/-6.7, 63.6+/-3.6, 81.6+/-3.5, and 78.0+/-4.1h (P<0.05). The interval from
      CIDR removal to ovulation was shorter and less variable in EB-treated groups; the
      interval from EB to ovulation was shortest (P<0.05) in the 12-h group. In
      summary, E-17beta or EB decreased both FSH and LH, but LH increased after 6h
      (despite elevated progesterone concentrations). Following CIDR removal, 1mg of EB
      effectively synchronized LH release, and ovulation (in intact cattle), but the
      interval from CIDR removal to EB treatment affected the time of ovulation.

PMID- 16797155
TI  - Accuracy of ultrasonography and 99mTc-sestamibi scintimammography for assessing
      axillary lymph node status in breast cancer patients. A prospective study.
AB  - AIMS: The aim of this study was to evaluate the sensitivity, specificity and
      accuracy of axillary ultrasonography (US) and (99m)Tc-sestamibi scintimammography
      (SSM) in patients with breast cancer (BC) undergoing curative surgery. METHODS: A
      series of 77 consecutive women (median age 54 years, range 36-70) with primary BC
      underwent both US and SSM from 2 to 15 (median 4) days prior to curative surgery.
      The results of imaging studies were compared against the final pathology. Breast
      conserving surgery with axillary node (AN) dissection was performed in 49 (63.6%)
      patients, and modified radical mastectomy in 28 (36.4%) patients, according to
      the tumour staging. RESULTS: Final pathology showed 5 pT1bN0, 1 pT1bN1, 28
      pT1cN0, 19 pT1cN1, 7 pT2N0, and 17 pT2N1 BC. Overall, 719 AN were removed of
      which 106 (14.7%) were metastatized nodes (median 3, range 1-5 per patient). The
      sensitivity, specificity and accuracy were 67.6%, 80.0%, and 74.0% for US, 78.4%,
      85.0%, and 81.8% for SSM, and 91.9%, 92.5%, and 92.2% for US and SSM together,
      respectively. There was a significant difference (p<0.05) in the number of
      metastatized AN between patients with metastases correctly detected and
      undetected by both US (3.1+/-1.3 vs. 2.0+/-0.7) and SSM (3.2+/-1.3 vs. 1.7+/
      0.7). CONCLUSIONS: Although the results of each diagnostic tests are strictly
      dependent on the number of the metastatized AN, the combination of axillary US
      and SSM is a sensitive low-cost procedure that should be suggested in all
      patients with BC, when a preoperative evaluation of the AN status is required.

PMID- 16797156
TI  - Preoperative transcatheter arterial chemoembolization reduces long-term survival
      rate after hepatic resection for resectable hepatocellular carcinoma.
AB  - AIMS: To study the effect of preoperative transcatheter arterial
      chemoembolization (TACE) on long-term survival after hepatic resection for
      hepatocellular carcinoma (HCC), we conducted a comparative analysis in 235 HCC
      patients who underwent hepatic resection with a curative intent. METHODS: We
      compared clinicopathologic background, mortality, and survival rates after
      hepatic resection between those who underwent preoperative TACE (n=109) and those
      who did not (n=126). RESULTS: One hundred and two patients in the TACE group
      (93.6%) received TACE only once. The mean interval between TACE and hepatic
      resection was 33.1days. Patients in the TACE group were younger than those in the
      non-TACE group, and liver cirrhosis and non-anatomical hepatic resection were
      more prevalent in this group. The 5-year overall survival rate after hepatic
      resection was significantly lower in the TACE group (28.6%) than in the non-TACE
      group (50.6%), especially in patients without cirrhosis or with stage I or II
      tumor. There was no difference between the two groups in mortality or disease
      free survival after hepatic resection. Multivariate analysis showed preoperative
      TACE, preoperative aspartate aminotransferase elevation, and microscopic portal
      invasion to be independent risk factors for a poor outcome after hepatic
      resection. CONCLUSIONS: Preoperative TACE should be avoided for patients with
      resectable HCC, especially for those without cirrhosis or with an early stage
      tumor.

PMID- 16797157
TI  - A case of HER-2(+) squamous cell breast carcinoma: an unusual presentation of an
      unusual clinical entity.

PMID- 16797158
TI  - Cox-2 expression on tissue microarray of breast cancer.
AB  - AIM: To measure cyclooxygenase-2 (Cox-2) expression in a series of breast cancers
      and evaluate its potential as a predictive marker for doxorubicin chemotherapy.
      PATIENTS AND METHODS: Cox-2 expression was analyzed in 178 node-positive patients
      treated with doxorubicin-based adjuvant chemotherapy by immunohistochemistry on
      tissue microarray (TMA). RESULTS: Cox-2 was over-expressed in 70 out of the 178
      invasive breast cancers. Cox-2 expression was significantly increased in
      undifferentiated tumors. There was no significant association between Cox-2 over
      expression and tumor size, histologic grade, and estrogen receptor expression.
      Disease-free survival and overall survival of the patients having Cox-2
      expressing tumor were significantly decreased when compared with the patients
      having Cox-2 negative tumor (p=0.009 for DFS, p=0.011 for OS). CONCLUSION: Cox-2
      expression may represent an aggressive phenotype of breast cancer which is
      resistant to doxorubicin.

PMID- 16797159
TI  - Early and late gastric cancer arising in the remnant stomach after distal
      gastrectomy.
AB  - AIM: Following distal gastrectomy, carcinogenesis has been suggested to result
      from gastroduodenal reflux. In this study, surgical cases of gastric cancer
      arising after distal gastrectomy were analyzed clinico-pathologically and the
      possible link to reflux examined. PATIENTS: Thirty-two patients (24 males, 8
      females; mean age, 68.7 years; age range, 33-84 years) with gastric cancer
      arising in the remnant stomach after gastrectomy (also known as gastric stump
      cancer) were included in this study. Patients were divided into two groups on the
      basis of the initial diagnosis (benign or malignant) prompting surgery, and
      distal gastrectomy reconstruction method (Billroth I or II). RESULTS: The
      interval between distal gastrectomy and detection of cancer in the remnant
      stomach of patients treated initially for a benign gastric condition vs.
      malignancy was 360+/-33.04 and 63+/-19.16 months (median+/-SE), respectively
      (p<0.0001). However, the benign and malignant groups did not differ significantly
      in the clinicopathological analysis of their stump cancers. All 10 patients in
      whom gastric cancer was diagnosed within five years of initial surgery had
      initially been surgically treated for malignancy. The interval between surgery
      and detection of gastric cancer in the Billroth I and Billroth II groups was 84+/
      26.67 and 276+/-44.26 months (median+/-SE), respectively (p<0.01). In the remnant
      stomach, cancer tended to occur near the site of gastrojejunostomy in the
      Billroth II group (p=0.05). Helicobacter pylori infection was only detected
      histologically in four patients who had undergone Billroth I reconstructions
      after distal gastrectomy for malignancy. CONCLUSION: After distal gastrectomy,
      careful periodic endoscopic examination for microcarcinoma is required in
      patients, particularly in those who undergo surgery for malignancy, to maximize
      detection of gastric cancer.

PMID- 16797160
TI  - Autoantibodies from Sjogren's syndrome induce activation of both the intrinsic
      and extrinsic apoptotic pathways in human salivary gland cell line A-253.
AB  - Sjogren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary
      and lachrymal glands, characterized by a high concentration of serum
      autoantibodies directed against nuclear and cytoplasmic antigens. It is known
      that autoantibodies can enter viable cells and this phenomenon has functional
      consequences including activation of apoptotic process. The objective of this
      work was to explore whether autoantibodies contained in IgG purified from Sjogren
      sera trigger apoptotic process in an experimental model represented by the human
      salivary gland cell line A-253. To define if the intrinsic or extrinsic pathways
      are activated, we examined which caspases are critical for inducing cell death.
      The results have demonstrated that morphological changes and DNA laddering,
      consistent with apoptotic cell death, occurred in A-253 cells treated with IgG
      from Sjogren sera. Sjogren IgG induced cleavage and activation of the effector
      caspase-3 and degradation of the caspase-3 substrate poly(ADP-ribose)polymerase.
      Both the intrinsic and extrinsic apoptotic pathways were activated, since both
      caspase-8 and caspase-9 cleavages occurred. In conclusion, autoantibodies
      contained in IgG purified from Sjogren sera mediate apoptosis of the A-253 cell
      line in a caspase-dependent manner.

PMID- 16797161
TI  - Cellular mechanism of U18666A-mediated apoptosis in cultured murine cortical
      neurons: bridging Niemann-Pick disease type C and Alzheimer's disease.
AB  - Neuronal cell death can occur by means of either necrosis or apoptosis. Both
      necrosis and apoptosis are generally believed to be distinct mechanisms of cell
      death with different characteristic features distinguished on the basis of their
      morphological and biochemical properties. The brain is the most cholesterol-rich
      organ in the body but not much is known about the mechanisms that regulate
      cholesterol homeostasis in the brain. Recently, several clinical and biochemical
      studies suggest that cholesterol imbalance in the brain may be a risk factor
      related to the development of neurological disorders such as Niemann-Pick disease
      type C (NPC) and Alzheimer's disease (AD). NPC is a fatal juvenile
      neurodegenerative disorder characterized by premature neuronal death and
      somatically altered cholesterol metabolism. The main biochemical manifestation in
      NPC is elevated intracellular accumulation of free cholesterol caused by a
      genetic deficit in cholesterol trafficking. The pharmacological agent, U18666A (3
      beta-[2-(diethylamino)ethoxy]androst-5-en-17-one), is a well-known class-2
      amphiphile which inhibits cholesterol transport. Cells treated with this agent
      accumulate intracellular cholesterol to massive levels, similar to that observed
      in cells from NPC patients. NPC and AD have some pathological similarities which
      may share a common underlying cause. AD is one of the most common types of
      dementia affecting the elderly. However, the molecular mechanisms of
      neurodegeneration in NPC and AD are largely unknown. This review provides a
      consolidation of work done using U18666A in the past half century and focuses on
      the implications of our research findings on the mechanism of U18666A-mediated
      neuronal apoptosis in primary cortical neurons, which may provide an insight to
      elucidate the mechanisms of neurodegenerative diseases, particularly NPC and AD,
      where apoptosis might occur through a similar mechanism.

PMID- 16797162
TI  - A double-blind comparison of risperidone, quetiapine and placebo in patients with
      schizophrenia experiencing an acute exacerbation requiring hospitalization.
AB  - OBJECTIVE: This study compared the effects of atypical antipsychotics
      (risperidone or quetiapine) with placebo and with each other in recently
      exacerbated patients with schizophrenia requiring hospitalization. METHODS: This
      international, randomized, double-blind study included a 2-week monotherapy phase
      followed by a 4-week additive therapy phase. Recently exacerbated patients with
      schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to
      risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses
      were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5,
      with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The
      main outcome measures were the total Positive and Negative Syndrome Scale (PANSS)
      and need for additional psychotropic medications. RESULTS: Monotherapy Phase: The
      combined atypical antipsychotic group (n = 308) reached borderline superiority to
      placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (
      24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the
      atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. 
      20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p <
      0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results
      were similar on other efficacy endpoints. Additive Therapy Phase: Additional
      psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than
      quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was
      18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was
      associated with more parkinsonism, akathisia, plasma prolactin changes, and
      weight gain; while quetiapine was associated with more somnolence, sedation,
      dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.
      CONCLUSION: While the combined atypical antipsychotic group did not experience
      greater improvements than the placebo group, risperidone, but not quetiapine, was
      significantly superior in all measured domains to placebo in the management of
      recently exacerbated hospitalized patients with schizophrenia or schizoaffective
      disorder, with no unexpected tolerability findings.

PMID- 16797163
TI  - Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics
      in schizophrenia: a randomized, placebo-controlled, double-blind investigation.
AB  - Cognitive impairment has the greatest impact on illness outcome in schizophrenia.
      The most significant challenge in schizophrenia therapeutics, thus, is to develop
      an efficacious treatment for cognitive impairments. Acetylcholinesterase
      inhibitors, such as Physostigmine and Rivastigmine, are considered effective
      treatments for cognitive decline in Alzheimer's Disease, where the loss of
      cholinergic neurons is thought to be responsible for various cognitive deficits.
      The current study investigated the cognitive effects of Rivastigmine given as an
      add-on therapy to antipsychotic-treated schizophrenia patients in a placebo
      controlled double-blind design. The study initially involved 40 patients, of
      which 21 patients (11 assigned to Rivastigmine and 10 assigned to placebo) agreed
      to continued participation, remained on the study drug, and underwent assessment
      of executive functioning, verbal skills, verbal and spatial working memory,
      attention and psychomotor speed on three occasions: (i) at baseline, and then
      (ii) after 12 weeks and (iii) 24 weeks of treatment with placebo or Rivastigmine.
      The results failed to reveal significant improvement on any cognitive measure
      with Rivastigmine treatment, compared with the placebo treatment. Some cognitive
      variables showed significant practice effects in both the placebo and
      Rivastigmine groups. No effects were noted in symptoms or side effects ratings.
      The beneficial cognitive effects of Rivastigmine seen in an open-label
      preliminary study are not substantiated by this study. Future studies should
      investigate the effects of other procholinergic drugs, such as Galantamine, which
      also act on the nicotine receptors and may produce stronger cognitive effects in
      schizophrenia.

PMID- 16797164
TI  - Efficacy and safety of zotepine for patients with treatment-resistant
      schizophrenia.

PMID- 16797165
TI  - Antimicrobial activities of human beta-defensins against Bacillus species.
AB  - Natural defences in the human body function to protect us from numerous
      environmental toxins and exposure to potential harmful biological agents. An
      important frontline defence is antimicrobial peptides. These peptides occur at
      environmental interfaces and serve to limit bacterial invasion. There has been
      little work comparing specific peptides as potential antimicrobial compounds. In
      this study, we evaluated the antimicrobial activity of peptides from the human
      beta-defensin (HBD) family against four species of Bacillus, chosen as models for
      Bacillus anthracis, a potential bioweapon. The impact of peptide concentration,
      sequence and protein binding was evaluated on their biological activity. The
      results indicated that HBD-3 was the most biologically active against Bacillus
      subtilis and Bacillus licheniformis, whilst HBD-2 was found to be most active
      against Bacillus cereus and Bacillus thuringiensis. Moreover, the antimicrobial
      activity of the peptides was directly related to peptide concentration and
      indirectly related to albumin concentration (i.e. protein binding).

PMID- 16797166
TI  - Spatial working memory in obsessive-compulsive disorder improves with clinical
      response: A functional MRI study.
AB  - To date, only a few studies have examined whether executive dysfunctions in
      obsessive-compulsive disorder (OCD) are state or trait dependent and almost none
      of these studies have used functional neuroimaging techniques. We conducted a
      functional MRI study before and after 12 weeks of pharmacological treatment in 14
      psychotropic-free patients with OCD without comorbidity. Subjects performed a
      spatial variant of a working memory task with four increasing levels of
      difficulty (n-back task). Responders and non-responders did not differ in
      clinical and demographical characteristics or brain activation patterns before
      treatment. Performance improved only in responders and was associated with a
      change in the overall pattern of brain activity during the task. We found no
      correlations between (changes in) scores on symptom scales, brain activity and
      performance. Our preliminary findings suggests that spatial working memory
      deficits in OCD and their functional anatomical correlates, as assessed with a
      spatial n-back task, are, at least to some extent, state dependent.

PMID- 16797167
TI  - A Serpin family gene, protease nexin-1 has an activity distinct from protease
      inhibition in early Xenopus embryos.
AB  - Protease nexin-1 (PN-1)/glia-derived nexin (GDN) is a member of the Serpin
      (serine proteinase inhibitor) family, and can inhibit thrombin, plasmin, and
      plasminogen activators. PN-1 has been shown to be a neuroprotective factor in a
      number of assay systems, and this activity has been assumed to be a function of
      its protease inhibitory function. Here, we report cloning and characterization of
      a Xenopus orthologue of PN-1 (xPN-1). xPN-1 was isolated in a functional screen
      of an egg cDNA library for factors that modify early axial patterning. xPN-1 is
      expressed maternally through late tadpole stages, and is expressed preferentially
      in the notochord, the pharyngeal endoderm, the otic vesicle, and the ventral
      region of the brain in tailbud embryos. Over-expression of xPN-1 causes defective
      gastrulation, inhibits convergent extension movements in activin induced animal
      caps, and inhibits expression of a distinct subset of activin induced
      mesendodermal markers. Interestingly, expression of point or deletion mutation of
      the Reactive Center Loop of xPN1,which is essential for the protease inhibitory
      activity of all serpins, had effects on Xenopus development indistinguishable
      from those of wild type xPN-1. These observations suggest the possibility that
      xPN-1 has a novel activity in addition to its established function as an
      inhibitor of serine proteases.

PMID- 16797168
TI  - An automated method for the extraction of regional data from PET images.
AB  - Manual drawing of regions of interest (ROIs) on brain positron emission
      tomography (PET) images is labour intensive and subject to intra- and inter
      individual variations. To standardize analysis and improve the reproducibility of
      PET measures, we have developed image analysis software for automated
      quantification of PET data. The method is based on the individualization of a set
      of standard ROIs using a magnetic resonance (MR) image co-registered with the PET
      image. To evaluate the performance of this automated method, the software-based
      quantification has been compared with conventional manual quantification of PET
      images obtained using three different PET radiotracers: [(11)C]-WAY 100635,
      [(11)C]-raclopride and [(11)C]-DASB. Our results show that binding potential
      estimates obtained using the automated method correlate highly with those
      obtained by trained raters using manual delineation of ROIs for frontal and
      temporal cortex, thalamus, and striatum (global intraclass correlation
      coefficient >0.8). For the three radioligands, the software yields time-activity
      data that are similar (within 8%) to those obtained by manual quantification,
      eliminates investigator-dependent variability, considerably shortens the time
      required for analysis and thus provides an alternative method for accurate
      quantification of PET data.

PMID- 16797169
TI  - Regional distribution of measurement error in diffusion tensor imaging.
AB  - The characterization of measurement error is critical in assessing the
      significance of diffusion tensor imaging (DTI) findings in longitudinal and
      cohort studies of psychiatric disorders. We studied 20 healthy volunteers, each
      one scanned twice (average interval between scans of 51 +/- 46.8 days) with a
      single shot echo planar DTI technique. Intersession variability for fractional
      anisotropy (FA) and Trace (D) was represented as absolute variation (standard
      deviation within subjects: SDw), percent coefficient of variation (CV) and intra
      class correlation coefficient (ICC). The values from the two sessions were
      compared for statistical significance with repeated measures analysis of variance
      or a non-parametric equivalent of a paired t-test. The results showed good
      reproducibility for both FA and Trace (CVs below 10% and ICCs at or above 0.70 in
      most regions of interest) and evidence of systematic global changes in Trace
      between scans. The regional distribution of reproducibility described here has
      implications for the interpretation of regional findings and for rigorous pre
      processing. The regional distribution of reproducibility measures was different
      for SDw, CV and ICC. Each one of these measures reveals complementary information
      that needs to be taken into consideration when performing statistical operations
      on groups of DT images.

PMID- 16797170
TI  - Complement activation by sulfonated poly(ethylene glycol)-acrylate copolymers
      through alternative pathway.
AB  - Previously, novel poly(ethylene glycol) (PEG) and sulfonated PEG acrylate (PEG
      SO(3)A/OA) copolymers were prepared as coating and/or blending materials for
      biomedical applications. Surfaces modified with copolymers exhibited increased
      anti-coagulation properties and decreased plasma adsorption level due to
      increased hydrophilic properties and reorientation characteristics of PEG/PEG
      SO(3)A chains in water phase. As continuation study, anti-complement effects of
      PEG-SO(3)/OA copolymers were investigated in vitro, and compared with those of
      low-density polyethylene (LDPE) and PEG/OA. C3 activation by PEG-SO(3)/OA samples
      was lower than that by PEG/OA samples, which was attributed to decreased surface
      nucleophile level of samples. PEG-SO(3)/OA samples increased inhibition of Bb
      production, resulting in decreased C5 activation. Owing to reduced activations of
      C3 and C5, PEG-SO(3)/OA samples markedly decreased SC5b-9 levels in plasma.

PMID- 16797171
TI  - Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy
      and quality attribute.
AB  - Transdermal drug delivery systems (TDDS), also known as "patches," are dosage
      forms designed to deliver a therapeutically effective amount of drug across a
      patient's skin. The adhesive of the transdermal drug delivery system is critical
      to the safety, efficacy and quality of the product. In the Drug Quality Reporting
      System (DQRS), the United States Food and Drug Administration (FDA) has received
      numerous reports of "adhesion lacking" for transdermal drug delivery systems.
      This article provides an overview of types of transdermals, their anatomy, the
      role of adhesion, the possible adhesion failure modes and how adhesion can be
      measured. Excerpts from FDA reports on the lack of adhesion of transdermal system
      products are presented. Pros and cons of in vitro techniques, such as peel
      adhesion, tack and shear strength, in vivo techniques used to evaluate adhesive
      properties are discussed. To see a decrease in "adhesion lacking" reports,
      adhesion needs to become an important design parameter and suitable methods need
      to be available to assess quality and in vivo performance. This article provides
      a framework for further discussion and scientific work to improve transdermal
      adhesive performance.

PMID- 16797172
TI  - Restrictive impairment in patients with asthma.
AB  - BACKGROUND: Patients with asthma have intermittent or persistent airflow
      obstruction, most often manifested spirometrically by reduced forced expiratory
      volume in 1s (FEV(1)) and FEV(1)/vital capacity (VC) ratio. In some patients, the
      VC may be reduced by air trapping, with an increase in functional residual
      capacity (FRC) and residual volume (RV) (pseudorestriction). We have reported 12
      asthmatic patients with reduced VC and no increase in RV, i.e., a true
      restrictive impairment [Gill et al. True restrictive impairment in bronchial
      asthma. Am J Respir Crit Care Med 1999:159:A652]. OBJECTIVES: To confirm previous
      observations of true restrictive impairment (not attributable to air trapping) in
      patients with asthma, and to estimate its frequency in an asthmatic population.
      METHODS: Review of pulmonary function tests and clinical records of all post
      pubertal patients diagnosed as asthma between January 2000 and September 2003 in
      a 184 bed inner city teaching hospital in Jamaica, Queens, New York. The clinical
      diagnosis of asthma was accepted when one or more of the following pulmonary
      function criteria were met: Positive bronchodilator response (BD), positive
      methacholine, repeated variability in spirometric values. Restriction was defined
      as decrease in total lung capacity (TLC) or decrease in VC with no increase in
      functional residual capacity (FRC) plus normal or high FEV(1)/FVC ratio. Patients
      with any clinical finding consistent with restriction, including a decreased
      diffusing capacity (DL) or obesity (BMI >30) were excluded. RESULTS: A total of
      100 of 413 (24%) patients with asthma had restriction; 21 of these met all
      exclusions (including DL and BMI) and 11 (of 46) patients with an increased BMI
      and normal DL normalized their FVC on BD therapy, demonstrating that their pre-BD
      restrictive impairment could not be attributed to obesity. Plethysmographic FRC
      was measured in 81 of the 100 patients with restriction and was increased in only
      seven. CONCLUSION: True restrictive impairment was noted in at least 32 of 413
      asthmatics (8%), consistent with previous observations in asthma and reactive
      airways dysfunction syndrome. This finding is not widely recognized and should
      not preclude the diagnosis of asthma, BD testing or appropriate therapy for
      asthma.

PMID- 16797173
TI  - Short-term and seasonal variations of exhaled and nasal NO in healthy subjects.
AB  - Nitric oxide (NO) is an important biological mediator with a variety of cellular
      and tissue functions. Fractional exhaled (FE(NO)) and nasal NO (FN(NO)) are known
      to be altered in several respiratory tract disease and disorders. However, there
      are rather few studies into the reproducibility of FE(NO) or FN(NO) measurements
      in healthy subjects. The aim of this study was to examine both short- and long
      term variations of FE(NO) and FN(NO). In addition to intraday, day-to-day and
      week-to-week variations, the seasonal variation was assessed. The data revealed
      that FE(NO) and FN(NO) levels were lower in the mornings compared to the
      afternoon values. There were clinically significant correlations in day-to-day
      (morning values 121.4+/-37.5 vs. 119.8+/-29.6, r=0.868, P=0.000), week-to-week
      (morning values 121.4+/-37.5 vs. 128.0+/-32.1, r=0.637, P=0.000) and seasonal
      (winter 133.5+/-29.7, summer 138.1+/-47.6, autumn 121.4+/-37.5, r=0.624, P=0.000)
      values of FN(NO). Day-to-day (morning values 14.6+/-6.7 vs. 14.2+/-5.1, r=0.784,
      P=0.000) week-to-week (morning values 14.6+/-6.7 vs. 15.4+/-7.3, r=0.738,
      P=0.000) and seasonal (autumn 14.6+/-7.2, winter 16.6+/-6.4, summer 17.4+/-8.0,
      r=0.709, P=0.000) levels of FE(NO) were also highly reproducible. Serial FE(NO)
      and FN(NO) measurements can be used in the monitoring of respiratory tract
      inflammation. Due to the diurnal variation of FE(NO) and FN(NO,) in long-term
      follow-up the measurements should be performed at the same time of day.

PMID- 16797174
TI  - Highly sensitive amperometric immunosensors for microcystin detection in algae.
AB  - The presence of cyanobacterial toxins in water and algae pose a health hazard for
      animals and humans, due to their tumour-promoting activity and carcinogen
      effects. The use of simple, rapid and reliable tools for routine analysis is
      becoming a necessity. With this purpose, our group has developed two
      electrochemical immunosensors for the detection of microcystin-LR (MC-LR) based
      on the affinity between this cyanotoxin and the corresponding monoclonal and
      polyclonal antibodies. A competitive direct enzyme-linked immunosorbent assays
      (ELISAs) was designed and, after validation of the approach on microtiter wells,
      screen-printed graphite electrodes were used as supports. Colorimetry was used to
      optimise the experimental parameters and to compare the performance of monoclonal
      and polyclonal antibodies. Afterwards, electrochemical measurements were
      performed at -200 mV (versus Ag/AgCl) using 5-methyl-phenazinium methyl sulfate
      (MPMS) as mediator for horseradish peroxidase (HRP), the enzymatic label of the
      competitor. The IC(50) values were 0.10 and 1.73 microgL(-1) for MAb and PAb,
      respectively. Whereas Mab provided higher sensitivities, the reproducibility was
      better when using PAb. The developed amperometric immunosensors were applied to
      the analysis of cyanobacterial samples from the Tarn River (Midi-Pyrenees,
      France) and the presence of MC was confirmed by the colorimetric protein
      phosphatase inhibition (PPI) assay and high performance liquid chromatography
      (HPLC). The limits of detection attained from the calibration curves and the
      results obtained for the real samples demonstrate the potential use of the
      immunosensors as screening tools for routine use in the assessment of water
      quality and the control of toxins in algae.

PMID- 16797175
TI  - Surface plasmon resonance biosensor for direct detection of antibody against
      Epstein-Barr virus.
AB  - This paper describes the direct label-free detection of antibodies against the
      Epstein-Barr virus (anti-EBNA) using a surface plasmon resonance (SPR) biosensor.
      The antibody detection was performed using the immunoreaction between anti-EBNA
      and a respective synthetic peptide (EBNA-1), which was conjugated with bovine
      serum albumin (BSA-EBNA) and immobilized on the sensor surface. Three
      immobilization chemistries for the attachment of BSA-EBNA were investigated to
      optimize ligand density and minimize loss of EBNA-1 immunoreactivity. The
      developed SPR biosensor functionalized with the optimal immobilization method was
      calibrated and characterized in terms of detection limit, reproducibility,
      regenerability and storability. It was demonstrated that the sensor is capable of
      detecting concentrations of anti-EBNA as low as 0.2 ng/ml (approximately 1 pM)
      both in buffer and 1% human serum and can be stored and regenerated for repeated
      use.

PMID- 16797176
TI  - Development of a plasma panel test for detection of human myocardial proteins by
      capillary immunoassay.
AB  - A chemiluminescence immunoassay for the detection of four heart marker proteins:
      myoglobin, creatine kinase mb [CKmb], troponin I [TnI], and fatty acid-binding
      protein [FABP], was designed. The immunoassay was based on enzyme-linked
      immunosorbent assay [ELISA] and antibodies immobilized in glass capillaries pre
      treated with 3-aminopropyltriethoxysilane. The protein bound to the antibody was
      detected by using an anti-protein-horseradish peroxidase [HRP] conjugate. The
      reaction of the HRP with luminal and hydrogen peroxide-based substrate generated
      the chemiluminescence and a photodiode detector was used to measure the light
      intensity. The same assay protocol was used to detect all four proteins.
      Ultrasound waves were used to improve the silanization of glass and the antibody
      immobilization process. The optimization of the duration and intensity of the
      ultrasound was performed for the myoglobin assay. Ultrasound improved the
      silanization procedure and the capillaries gave an approximately 2.5 times
      greater ELISA response. Ultrasound also improved the sensitivity by approximately
      100% when monoclonal antibody was immobilized on a glass capillary. Calibration
      curves corresponding to analyte concentrations ranging from 2.4 to 2400 ng/ml in
      plasma samples were recorded. The detection limits were in the region of 1.2
      myoglobin, 0.6 CKmb, 5.6 TnI, and 4 ng/ml FABP in plasma with a coefficient of
      variation of 3-9.9%.

PMID- 16797177
TI  - The social lives of migrating cells in Drosophila.
AB  - Studies of cell migration in Drosophila are yielding insights into the complex
      interactions migrating cells have with each other and with the cells in their
      environment. Intriguing links between factors that promote cell migration and
      those that control cell survival have been reported recently. For example,
      migrating germ cells compete with the surrounding somatic tissue for the
      substrate of the lipid phosphate phosphatases encoded by the genes Wunen and
      Wunen2. Germ cells take up the dephosphorylated lipid and require it for their
      survival. In addition, the secreted growth factors called PVFs, previously
      thought to guide the migrations of hemocytes in the embryo, were found to
      function instead predominantly as survival factors. And in border cells, DIAP1
      and Dronc, two proteins known mainly for their ability to regulate cell death,
      were found to control cell migration.

PMID- 16797178
TI  - Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone
      (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG).
AB  - We have recently taken advantage of the unique power of DNA microarrays to
      compare the genomic expression profile of tetrahydrogestrinone (THG) with that of
      dihydrotestosterone (DHT), the most potent natural androgen, thus clearly
      demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled
      Substances Act has been modified to include androstenedione (4-dione) as an
      anabolic steroid. However, despite the common knowledge that
      dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been
      excluded from the list of anabolic steroids. We thus used the same DNA microarray
      technology to analyze the expression profile of practically all the 30,000 genes
      of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive
      tissues. Daily subcutaneous injections of DHT (0.1mg) or DHEA (3mg) for 1 month
      in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate,
      seminal vesicle and preputial gland weight (p<0.01 for all tissues). As early as
      24h after single injection of the two steroids, 878, 2681 and 14 probe sets were
      commonly stimulated or inhibited (p<0.01, change> or =30%), in the prostate
      (ventral+dorsal), seminal vesicles and preputial glands, respectively, compared
      to tissues from gonadectomized control animals. After 7 days of daily treatment
      with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the
      same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets
      were modulated, respectively. In analogy with the data obtained with THG, the
      present microarray data provide an extremely precise and unquestionable genomic
      signature and proof of the androgenic/anabolic activity of DHEA. Such data add to
      the literature showing that DHEA is transformed into androgens in the human
      peripheral tissues as well as in laboratory animal species, including the monkey,
      thus exerting potent androgenic/anabolic activity. The present microarray
      approach to identify anabolic compounds is applicable to all potential
      androgenic/anabolic compounds.

PMID- 16797179
TI  - Effect of ormeloxifene on ovariectomy-induced bone resorption, osteoclast
      differentiation and apoptosis and TGF beta-3 expression.
AB  - Effect of ormeloxifene, a multifunctional selective estrogen receptor modulator,
      on prevention of ovariectomy-induced bone resorption in retired breeder female
      rats, osteoclastogenesis using bone marrow cells from adult Balb/c mice cultured
      in presence of M-CSF and RANKL, osteoclast apoptosis using terminal
      deoxynucleotidyl transferase fragment end labeling and TGF beta-3 expression were
      investigated. Raloxifene, a benzothiophene reported to mimic effects of estrogen
      in bone, and estradiol were used for comparison. Ormeloxifene (10(-6) and 10(
      8)M) significantly inhibited osteoclastogenesis (P<0.001 versus vehicle control)
      as evidenced by lower number of TRAP-positive osteoclasts in bone marrow cultures
      and caused apoptosis of osteoclasts. The effect was almost equivalent to that
      observed in presence of estradiol-17 beta, except that significant number of
      cells undergoing apoptosis was evident even at 10(-9)M concentration of estradiol
      17 beta (P<0.001). Raloxifene, though inhibited osteoclastogenesis at much lower
      concentrations (10(-8) to 10(-12)M; P<0.001), failed to cause apoptosis of
      osteoclasts at any of the concentrations used. While ormeloxifene, raloxifene and
      ethynylestradiol significantly prevented ovariectomy-induced bone loss in vivo in
      retired breeder female rats, prevention of ovariectomy-induced decrease in BMD
      and trabecular network of proximal tibia, calcium and phosphorus levels in femur
      and tibia and prevention of ovariectomy-induced down-regulation of TGF beta-3
      expression in lumbar vertebrae was of lower order in raloxifene- than
      ormeloxifene- or ethynylestradiol-supplemented females. Both the SERMs, however,
      produced considerable estrogenic effects at the uterine level as evidenced by
      increase in weight, total and endometrial area and luminal epithelial cell
      height; the effect being generally greater in raloxifene- than ormeloxifene
      treated rats. Findings demonstrate that inhibition of estrogen-deficiency
      osteoporosis by ormeloxifene, as in case of estradiol, was mediated via
      inhibition of osteoclastogenesis, apoptosis of osteoclasts and up-regulation of
      TGF beta-3 expression. Raloxifene, though effective in inhibiting
      osteoclastogenesis in vitro at much lower concentrations, was not only less
      potent in preventing ovariectomy-induced bone loss in retired breeder female rats
      in vivo but also appeared to have a different mechanism of action than
      ormeloxifene and estradiol.

PMID- 16797180
TI  - Antifungal activity and enhancement of plant growth by Bacillus cereus grown on
      shellfish chitin wastes.
AB  - Bacillus cereus QQ308 produced antifungal hydrolytic enzymes, comprising
      chitinase, chitosanase and protease, when grown in a medium containing shrimp and
      crab shell powder (SCSP) produced from marine waste. The growth of the plant
      pathogenic fungi Fusarium oxysporum, Fusarium solani, and Pythium ultimum were
      considerably affected by the presence of the QQ308 culture supernatant. The
      supernatant inhibited spore germination and germ tube elongation of F. oxysporum,
      F. solani, and P. ultimum. The increase in the growth time of the fungal culture
      was associated with a gradual decrease in inhibition. Besides antifungal
      activity, QQ308 enhanced growth of Chinese cabbage. These characteristics were
      unique among known strains of B. cereus. To our knowledge, this is the first
      report on the antifungal and Chinese cabbage growth enhancing compounds produced
      by B. cereus.

PMID- 16797181
TI  - Atypical presentations of spinal muscular atrophy type III (Kugelberg-Welander
      disease).
AB  - Spinal muscular atrophy type III (SMA III, Kugelberg-Welander disease) typically
      presents with symmetric proximal weakness, areflexia, and hypotonia. We present
      four children with spinal muscular atrophy type III who had atypical phenotypes.
      Three patients clearly had asymmetric weakness at presentation and two had upper
      motor neuron signs in the lower extremities (one patient had both features). Two
      of the patients had prolonged evaluations before the diagnosis was made. All
      patients had Gowers signs and two had pes planus. In patients with proximal
      muscle weakness the presence of asymmetrical weakness, upper motor neuron signs,
      or both, may be compatible with spinal muscular atrophy type III. The diagnosis
      of spinal muscular atrophy should be considered when other possibilities have
      been excluded.

PMID- 16797182
TI  - Conserved ribonuclease, Eri1, negatively regulates heterochromatin assembly in
      fission yeast.
AB  - RNA interference (RNAi) is a conserved silencing mechanism that has widespread
      roles in RNA degradation, translational repression, and the epigenetic control of
      chromatin structure [1]. In fission yeast, heterochromatin assembly requires RNAi
      machinery and is initiated by small interference RNAs (siRNAs) derived from
      heterochromatic regions and by the RNA-induced transcriptional silencing (RITS)
      complex [2-7]. Although recent studies have been successful in uncovering the
      functions of effector complexes in the RNAi pathway [4, 5, 8-10], exactly how
      heterochromatic siRNAs are processed and function in assembling heterochromatin
      remains unclear. In this study we focused on a conserved ribonuclease, Eri1,
      which was originally identified as a negative regulator of RNAi in C. elegans
      [11], and show the importance of the Eri1 protein in RNAi-mediated
      heterochromatin assembly in fission yeast. Eri1 specifically degrades double
      stranded siRNAs through two functional domains and represses the accumulation of
      cellular siRNAs in vivo. Deletion of eri1(+) causes an increase in siRNAs
      associated with the RITS complex and enhances heterochromatic silencing, which is
      accompanied by increased levels of histone H3-K9 methylation and the Swi6
      protein. Our findings suggest that the fission yeast Eri1 controls the
      accumulation of heterochromatic siRNAs and negatively regulates the RNAi-mediated
      heterochromatin assembly.

PMID- 16797183
TI  - Analysis of the healthy rabbit lens surface using MAC Mode atomic force
      microscopy.
AB  - In this investigation healthy rabbit crystalline lenses were characterized by
      atomic force microscopy (AFM). The lenses were cut in slices with thickness with
      1mm and thus, put after cortex distinct regions of nucleus and cortex for AFM
      examination. AFM analysis were carried out using a PicoSPM I operating in Mac
      Mode. We obtained topographic images of rabbit lenses and a quantitative analysis
      of the width and height of fibers for nucleus and cortex regions. The
      longitudinal section analysis of fibers in the nucleus region indicated
      structures with an average width of 200nm and average height of 200nm. The
      intershells distance was determined as 4microm. Fiber cell cross-section
      dimensions, longitudinal and transverse widths, could be estimated in these
      regions from the AFM images. Structures with average widths as small as 1.0microm
      are observed in the nucleus; the intershell distance is 4.0microm. In cortical
      regions, hexagonal structures with average longitudinal and transverse widths of
      5.0mum and 3.0mum, respectively, were identified. Three-dimensional images of
      tissue sections with resolution on a nanometer scale were obtained. The potential
      of AFM analysis for characterizing healthy and pathologic lens tissues is
      discussed.

PMID- 16797184
TI  - Identifying spectrometric signatures of phosphate deposits and enclosing
      sediments in Al-Awabed area, Northern Palmyrides, Central Syria, by the use of
      statistical factor analysis.
AB  - In previous published research, a factor analysis approach has been applied to
      airborne spectrometric data of Al-Awabed area, Northern Palmyrides, Syria. A
      model of four factors (F1, F2, F3 and F4) has proven to be sufficient to
      represent the acquired data, where 94% of the total data variance is explained. A
      powerful tool for direct differentiation of various rocks units is obtained
      through the mapping of these four factors, where a scored lithological map
      including 11 radiometric units is established. Ninety nine rock samples have been
      taken according to the four factors to be analyzed by the gamma-spectrometry
      technique in order to determine their content of eU, eTh and K%. The analysis of
      65 samples according to F1 indicates that uranium concentration varies between
      2.74 and 123.3 ppm with an average of 58.85 ppm and a standard deviation of 32.53
      ppm. The analysis of 18 samples taken according to F2 indicates that K%
      concentration varies between 0.001 and 0.324 with an average of 0.145 and a
      standard deviation of 0.122. The analysis of 16 samples taken according to F3
      indicates that K% concentration varies between 0.024 and 0.558 with an average of
      0.227 and a standard deviation of 0.133. These gamma-results are expected and fit
      very well with the results obtained by the factor analysis approach. Therefore,
      the validity and efficacy of the factor analysis approach, to be widely used as a
      guide in exploration and smart sampling for mining programs, are well
      demonstrated. The established phosphate maps show a width extension and
      distribution, and clearly indicate the potential of the research area, and it
      merits to be followed by economic exploration.

PMID- 16797185
TI  - A suite of parallel vectors for baculovirus expression.
AB  - The expression of proteins using recombinant baculoviruses is a mature and widely
      used technology. However, some aspects of the technology continue to detract from
      high throughput use and the basis of the final observed expression level is
      poorly understood. Here, we describe the design and use of a set of vectors
      developed around a unified cloning strategy that allow parallel expression of
      target proteins in the baculovirus system as N-terminal or C-terminal fusions.
      Using several protein kinases as tests we found that amino-terminal fusion to
      maltose binding protein rescued expression of the poorly expressed human kinase
      Cot but had only a marginal effect on expression of a well-expressed kinase IKK
      2. In addition, MBP fusion proteins were found to be secreted from the expressing
      cell. Use of a carboxyl-terminal GFP tagging vector showed that fluorescence
      measurement paralleled expression level and was a convenient readout in the
      context of insect cell expression, an observation that was further supported with
      additional non-kinase targets. The expression of the target proteins using the
      same vectors in vitro showed that differences in expression level were wholly
      dependent on the environment of the expressing cell and an investigation of the
      time course of expression showed it could affect substantially the observed
      expression level for poorly but not well-expressed proteins. Our vector suite
      approach shows that rapid expression survey can be achieved within the
      baculovirus system and in addition, goes some way to identifying the underlying
      basis of the expression level obtained.

PMID- 16797186
TI  - Discriminating imagined from perceived information engages brain areas implicated
      in schizophrenia.
AB  - Some of the symptoms of schizophrenia may reflect a difficulty discriminating
      between information that was perceived from the outside world and information
      that was imagined. This study used fMRI to examine the brain regions associated
      with this reality monitoring ability in healthy volunteers, who recollected
      whether information had previously been perceived or imagined, or whether
      information had been presented on the left or right of a monitor screen. Recent
      studies have suggested that schizophrenia may be associated particularly with
      dysfunction in medial anterior prefrontal cortex, thalamus, and cerebellum. In
      our data, activation in all three of these regions of interest was significantly
      greater during recollection of whether stimuli had been perceived or imagined
      versus recollection of stimulus position. In addition, reduced prefrontal
      activation was associated with the same misattribution error that has been
      observed in schizophrenia. These results indicate a possible link between the
      brain areas implicated in schizophrenia and the regions supporting the ability to
      discriminate between perceived and imagined information.

PMID- 16797187
TI  - Aging: compensation or maturation?
AB  - Neuroimaging studies of healthy aging often reveal differences in neural
      activation patterns between young and elderly groups for episodic memory tasks,
      even though there are no differences in behavioral performance. One explanation
      typically offered is that the elderly compensate for their memory deficiencies
      through the recruitment of additional prefrontal regions. The present study of
      healthy aging compared magnetoencephalographic (MEG) time-courses localized to
      specific cortical regions in two groups of subjects (20-29 years and >or=65
      years) during a visual delayed-match-to-sample (DMS) task. MR morphometrics and
      neuropsychological test results were also examined with the hope of providing
      insight into the nature of the age-related differences. The behavioral results
      indicated no differences in performance between young and elderly groups.
      Although there was a main effect of age on the latency of the initial peak in
      primary/secondary visual cortex, these longer latencies were not correlated with
      the performance of elderly on the DMS task. The lateral occipital gyrus (LOG)
      revealed qualitatively different patterns of activity for the two age groups
      corroborated by neuropsychological test results. Morphometric results for the
      young versus elderly groups revealed less white (WM) and gray matter (GM) volumes
      in the frontal lobes of the elderly. When a group of middle-aged subjects (33-43
      years) was included in the morphometric analyses, the middle-aged subjects
      revealed statistically greater WM volumes in frontal and parietal cortex
      suggesting immature WM tracts in the young. Perhaps our elderly utilized a
      different strategy compared to the young due to the different brain maturation
      levels of these groups.

PMID- 16797188
TI  - Automated segmentation of multiple sclerosis lesion subtypes with multichannel
      MRI.
AB  - PURPOSE: To automatically segment multiple sclerosis (MS) lesions into three
      subtypes (i.e., enhancing lesions, T1 "black holes", T2 hyperintense lesions).
      MATERIALS AND METHODS: Proton density-, T2- and contrast-enhanced T1-weighted
      brain images of 12 MR scans were pre-processed through intracranial cavity (IC)
      extraction, inhomogeneity correction and intensity normalization. Intensity-based
      statistical k-nearest neighbor (k-NN) classification was combined with template
      driven segmentation and partial volume artifact correction (TDS+) for
      segmentation of MS lesions subtypes and brain tissue compartments. Operator
      supervised tissue sampling and parameter calibration were performed on 2 randomly
      selected scans and were applied automatically to the remaining 10 scans. Results
      from this three-channel TDS+ (3ch-TDS+) were compared to those from a previously
      validated two-channel TDS+ (2ch-TDS+) method. The results of both the 3ch-TDS+
      and 2ch-TDS+ were also compared to manual segmentation performed by experts.
      RESULTS: Intra-class correlation coefficients (ICC) of 3ch-TDS+ for all three
      subtypes of lesions were higher (ICC between 0.95 and 0.96) than that of 2ch-TDS+
      for T2 lesions (ICC = 0.82). The 3ch-TDS+ also identified the three lesion
      subtypes with high specificity (98.7-99.9%) and accuracy (98.5-99.9%).
      Sensitivity of 3ch-TDS+ for T2 lesions was 16% higher than with 2ch-TDS+.
      Enhancing lesions were segmented with the best sensitivity (81.9%). "Black holes"
      were segmented with the least sensitivity (62.3%). CONCLUSION: 3ch-TDS+ is a
      promising method for automated segmentation of MS lesion subtypes.

PMID- 16797189
TI  - Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to
      evolving optic nerve injury in mice with retinal ischemia.
AB  - Decreased axial (lambda(||)) and increased radial (lambda( perpendicular))
      diffusivity have been shown to reflect axonal and myelin injury respectively. In
      the present study, evolving white matter injury within the optic nerves of mice
      with retinal ischemia was examined by in vivo and ex vivo measurements of
      lambda(||) and lambda( perpendicular). The results show that at 3 days after
      retinal ischemia, a 33% decrease in vivo and a 38% decrease ex vivo in lambda(||)
      without change in lambda( perpendicular) was observed in the injured optic nerve
      compared to the control, suggestive of axonal damage without myelin injury. At 14
      days, both in vivo and ex vivo measured lambda( perpendicular) increased
      significantly to 220-240% of the control level in the injured optic nerve
      suggestive of myelin damage. In contrast, the axonal injury that was clearly
      detected in vivo as a significantly decreased lambda(||) (33% decrease) was not
      as clearly detected by ex vivo lambda(||) (17% decrease). The current findings
      suggest that ex vivo lambda( perpendicular) is comparable to in vivo lambda(
      perpendicular) in detecting myelin injury. However, the structural changes
      resulting from axonal damage causing the decreased in vivo lambda(||) may not be
      preserved ex vivo in the fixed tissues. Despite the accurate depiction of the
      pathology using lambda(||) and lambda( perpendicular) in vivo, the use of ex vivo
      lambda(||) to extrapolate the status of axonal injury in vivo would require
      further investigation.

PMID- 16797190
TI  - Aging is associated with contrasting changes in local and distant cortical
      connectivity in the human motor system.
AB  - Pathophysiological changes in neurological and neuropsychiatric diseases are
      increasingly described in terms of abnormal network connectivity. However, the
      anatomical integrity and efficacy of connections among multiple brain regions
      change with aging, even in healthy adults. We combined low-frequency transcranial
      magnetic stimulation and positron emission tomography to study the age-related
      changes in regional activation and effective connectivity, associated with
      voluntary action by healthy adults between 22 and 68 years old. Contrasting
      effects of aging on the motor network were seen using analyses of regional
      activation, effective connectivity mediating task-related neuronal activation and
      effective connectivity in response to transcranial magnetic stimulation. Low
      frequency rTMS reduced cerebral blood flow during both movement and resting
      conditions, at the site of stimulation and neighboring frontal cortex. Aging was
      associated with increased movement-related activation in premotor cortex,
      bilaterally. Increasing age also increased the susceptibility of the cortex to
      the inhibitory effects of rTMS, at the site of stimulation and its contralateral
      homologue. Moreover, older subjects showed enhanced local effective connectivity,
      centered on the left premotor cortex, but reduced effective connectivity between
      distant motor-related cortical areas. We discuss these results in relation to the
      HAROLD model of aging and propose that there are differential effects of aging on
      local and distributed neuronal subpopulations in the motor network. This
      differential effect of aging has important implications for the study of
      neurodegenerative and cerebrovascular diseases that primarily affect older
      people, as well as our understanding of the normal aging process.

PMID- 16797191
TI  - Increased oxygen consumption in the somatosensory cortex of alpha-chloralose
      anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla.
AB  - The significance of changes in cerebral oxygen consumption in focally activated
      brain tissue is still controversial. Since the rate of cerebral oxygen
      consumption is tightly coupled to that of tricarboxylic acid cycle which can be
      measured from the turnover kinetics of [4-(13)C]glutamate using in vivo
      (1)H{(13)C} magnetic resonance spectroscopy, changes in tricarboxylic acid cycle
      flux rate were assessed in primary somatosensory cortex of alpha-chloralose
      anesthetized rats during electrical forepaw stimulation. With markedly improved
      (1)H{(13)C} magnetic resonance spectroscopy technique and the use of high
      magnetic field strength of 11.7 T accessible to the current study, [4
      (13)C]glutamate at 2.35 ppm was spectrally resolved from overlapping resonances
      of [4-(13)C]glutamine at 2.46 ppm and [2-(13)C]GABA at 2.28 ppm as well as the
      more distal [3-(13)C]glutamate and [3-(13)C]glutamine. The results showed a
      significantly increased V(TCA) in focally activated primary somatosensory cortex
      during forepaw stimulation, corresponding to approximately 51 +/- 27% (n = 6,
      mean +/- SD) increase in cerebral oxygen consumption rate. Considering the high
      efficiency in producing adenosine triphosphate by oxidative metabolism of
      glucose, the results demonstrate that aerobic oxidative metabolism provides the
      majority of energy required for cerebral focal activation in alpha-chloralose
      anesthetized rats subjected to forepaw stimulation.

PMID- 16797192
TI  - Systematics of Ficedula flycatchers (Muscicapidae): a molecular reassessment of a
      taxonomic enigma.
AB  - Ficedula flycatchers are a group of species with disparate plumages and habits
      that have proven a challenge for taxonomists since the first description of the
      genus [Brisson, M.J., 1760. Ornithologia sive synopsis methodica sistens Avium
      divisionem in ordines. 2: ilxvii, 1-516]. The most recent evaluation was
      conducted by Vaurie (Vaurie, C., 1953. A generic revision of flycatchers of the
      tribe Muscicapini. Bull. Amer. Mus. Nat. Hist. 100, 453-538), who used
      morphological and behavioral characters, as well as distributional data to
      consider relationships among Ficedula species, between ostensible "groupings"
      within the genus, and between Ficedula and its presumed sister genera. Since
      1953, no study has sought to evaluate relationships among Ficedula species, and
      only five Palearctic species have been studied to any extent. Here, using three
      mitochondrial genes, we provide the first assessment of phylogenetic
      relationships among Ficedula species to include the consideration of presumed
      subgenera or "groupings," and between Ficedula and its putative sister genera.
      Our results suggest that Ficedula is not monophyletic; Ficedula solitaris was
      originally placed in the genus Anthipes, and our results suggest that both
      solitaris and its sister monileger should be placed in Anthipes, near Niltava.
      The remaining Ficedula species for which we had samples form a well-supported
      clade that includes Muscicapella (a monotypic genus of previously uncertain
      affinities). The genus Tarsiger is the sister genus to Ficedula.

PMID- 16797193
TI  - Heterogeneous colonization pattern of European Cyprinids, as highlighted by the
      dace complex (Teleostei: Cyprinidae).
AB  - The dace (Leuciscus leuciscus), with a very large geographic distribution all
      over Europe, represents an interesting species model for studies of the global
      mechanisms underlying aquatic system biodiversity. To assess the congruence with
      the past colonization process hypothesis of the freshwater fauna in Western
      Europe, we investigated the evolutionary history of this species, by integrating
      morphological variation (eight meristic characters), mitochondrial (cytochrome b,
      16S rDNA and control region, over a total of 2169 bp) and nuclear (12 allozymes
      loci) phylogenetic relationships, and investigating population dynamics via
      expansion, migration, bottleneck, and divergence time analyses. We carried out
      nested clade phylogeographic analysis for a total of 663 specimens from 31
      populations taken from all over the distribution area. Unlike previous studies,
      we found that L. leuciscus is currently constituted by five lineages belonging to
      two clades (yielding 6.3% of pairwise divergence). The relationships between
      these lineages were accounted for by complex biogeographical patterns due to
      Pliocene and Pleistocene paleoclimatic events, validating the identification of
      new glacial refuges for freshwater fish in Western Europe. Finally, we
      demonstrated hybridization between L. leuciscus and Leuciscus idus.

PMID- 16797194
TI  - Prediction of collagen orientation in articular cartilage by a collagen
      remodeling algorithm.
AB  - OBJECTIVE: Tissue engineering is a promising method to treat damaged cartilage.
      So far it has not been possible to create tissue-engineered cartilage with an
      appropriate structural organization. It is envisaged that cartilage tissue
      engineering will significantly benefit from knowledge of how the collagen fiber
      orientation is directed by mechanical conditions. The goal of the present study
      is to evaluate whether a collagen remodeling algorithm based on mechanical
      loading can be corroborated by the collagen orientation in healthy cartilage.
      METHODS: According to the remodeling algorithm, collagen fibrils align with a
      preferred fibril direction, situated between the positive principal strain
      directions. The remodeling algorithm was implemented in an axisymmetric finite
      element model of the knee joint. Loading as a result of typical daily activities
      was represented in three different phases: rest, standing and gait. RESULTS: In
      the center of the tibial plateau the collagen fibrils run perpendicular to the
      subchondral bone. Just below the articular surface they bend over to merge with
      the articular surface. Halfway between the center and the periphery, the collagen
      fibrils bend over earlier, resulting in a thicker superficial and transitional
      zones. Near the periphery fibrils in the deep zone run perpendicular to the
      articular surface and slowly bend over to angles of -45 degrees and +45 degrees
      with the articular surface. CONCLUSION: The collagen structure as predicted with
      the collagen remodeling algorithm corresponds very well with the collagen
      structure in healthy knee joints. This remodeling algorithm is therefore
      considered to be a valuable tool for developing loading protocols for tissue
      engineering of articular cartilage.

PMID- 16797195
TI  - Bronchial arterial imaging using helical computed tomography.
AB  - The bronchial arteries, which provide the systemic arterial supply to the lungs,
      are involved in a variety of disease processes in humans, including congenital
      disorders, infection, and pulmonary thromboembolism. In these conditions, the
      bronchial arteries hypertrophy and bronchial blood flow increases. Consequently,
      in many disorders, such as bronchiectasis, the bronchial arteries are a frequent
      source of haemoptysis, which may be massive and life-threatening. Evaluation of
      the bronchial circulation has typically required invasive imaging with
      angiography to determine the location of bleeding. Non-invasive assessment of
      bronchial arterial anatomy and morphology is currently being investigated with
      the use of helical computed tomography (CT). We evaluated eight patients with
      various lung diseases with helical CT (GE Medical Systems, LS16, Milwaukee, WI)
      to determine the imaging features of the bronchial circulation. Non-ionic
      contrast medium (iopromide) was injected intravenously (80-1000ml/30s) and
      scanning was triggered once contrast material was present in the pulmonary artery
      (average delay=15s) or ascending aorta (average delay=20s). Detector collimation
      (16-row unit) was 10mm. Imaging parameters included a section thickness of 0.6mm,
      kilovolt peak of 120, 150-440mA, pitch factor of 1.375, matrix of 512x512, and
      tube rotation time of 0.8s. The images were reconstructed and scanned
      isotropically (Advantage Workstation 4.1,GE Medical Systems). We conclude that
      helical computed tomography may provide a non-invasive means of evaluating the
      bronchial arteries and their role in pulmonary disease processes.

PMID- 16797196
TI  - Engineering of the redox imbalance of Fusarium oxysporum enables anaerobic growth
      on xylose.
AB  - Dissimilatory nitrate reduction metabolism, of the natural xylose-fermenting
      fungus Fusarium oxysporum, was used as a strategy to achieve anaerobic growth and
      ethanol production from xylose. Beneficial alterations of the redox fluxes and
      thereby of the xylose metabolism were obtained by taking advantage of the
      regeneration of the cofactor NAD(+) during the denitrification process. In batch
      cultivations, nitrate sustained growth under anaerobic conditions (1.21 g L(-1)
      biomass) and simultaneously a maximum yield of 0.55 moles of ethanol per mole of
      xylose was achieved, whereas substitution of nitrate with ammonium limited the
      growth significantly (0.15 g L(-1) biomass). Using nitrate, the maximum acetate
      yield was 0.21 moles per mole of xylose and no xylitol excretion was observed.
      Furthermore, the network structure in the central carbon metabolism of F.
      oxysporum was characterized in steady state. F. oxysporum grew anaerobically on
      [1-(13)C] labelled glucose and unlabelled xylose in chemostat cultivation with
      nitrate as nitrogen source. The use of labelled substrate allowed the precise
      determination of the glucose and xylose contribution to the carbon fluxes in the
      central metabolism of this poorly described microorganism. It was demonstrated
      that dissimilatory nitrate reduction allows F. oxysporum to exhibit typical
      respiratory metabolic behaviour with a highly active TCA cycle and a large demand
      for NADPH.

PMID- 16797197
TI  - General and specific functions of exonic splicing silencers in splicing control.
AB  - Correct splice site recognition is critical in pre-mRNA splicing. We find that
      almost all of a diverse panel of exonic splicing silencer (ESS) elements alter
      splice site choice when placed between competing sites, consistently inhibiting
      use of intron-proximal 5' and 3' splice sites. Supporting a general role for ESSs
      in splice site definition, we found that ESSs are both abundant and highly
      conserved between alternative splice site pairs and that mutation of ESSs located
      between natural alternative splice site pairs consistently shifted splicing
      toward the intron-proximal site. Some exonic splicing enhancers (ESEs) promoted
      use of intron-proximal 5' splice sites, and tethering of hnRNP A1 and SF2/ASF
      proteins between competing splice sites mimicked the effects of ESS and ESE
      elements, respectively. Further, we observed that specific subsets of ESSs had
      distinct effects on a multifunctional intron retention reporter and that one of
      these subsets is likely preferred for regulation of endogenous intron retention
      events. Together, our findings provide a comprehensive picture of the functions
      of ESSs in the control of diverse types of splicing decisions.

PMID- 16797198
TI  - Presentation and outcome of infective endocarditis in Spain: a retrospective
      study.
AB  - OBJECTIVE: To analyze cases of infective endocarditis in patients who attended
      the Hospital General de Castellon, Spain, between 1999 and 2004. METHODS: This
      was a retrospective study. Demographic and clinical characteristics were
      assessed, variation in presentation over time was analyzed, and factors
      influencing outcome were determined. RESULTS: A total of 54 cases in 48 patients
      were included; 33 (61%) were in men. The median patient age was 62 years.
      Infective endocarditis occurred on a native valve in 36 cases (67%), a mechanical
      prosthetic valve in 12 (22%), and a pacemaker in six (11%). The mitral valve was
      the most commonly affected site. Transthoracic and/or transesophageal
      echocardiography showed a vegetation in 45 (83%) cases, moderate or severe
      valvular regurgitation in 27 (50%), and intracardiac destructive lesions in five
      (9%). The outcome in 15 (28%) cases was death, and multivariate analysis
      disclosed significantly increased risk of death associated with older age, lower
      serum albumin, and higher white blood cell count. CONCLUSIONS: This study
      confirmed the protean nature of infective endocarditis, and identified several
      factors predictive of mortality including advanced age, low serum albumin, and
      high white blood cell count.

PMID- 16797199
TI  - A human origin type II strain of Toxoplasma gondii causing severe encephalitis in
      mice.
AB  - Despite its capacity for sexual reproduction and global distribution, Toxoplasma
      gondii has a highly clonal structure, with the majority of isolates belonging to
      three distinct clonal types. Congenital toxoplasmosis has been associated with
      type I and type II strains. We here present the first characterization of a T.
      gondii strain (BGD1) from South-East Europe, isolated from the umbilical blood of
      a 24-week-old fetus in Serbia. Genotyping, performed by PCR-RFLP using a set of
      nested PCR markers (5'SAG2, 3'SAG2, BTUB, SAG3, and GRA6), showed that the BGD1
      strain possessed a type II genotype. The cytokine patterns in Swiss-Webster mice
      inoculated with brain cysts of BGD1 and the prototype type II ME49 strain were
      similar until 180 days post-infection, with highly elevated IFN-gamma, IL-12 and
      IL-10 by d7 and decreasing thereafter. While both strains induced pneumonia and
      hepatitis in acute infection (d14), chronic infection (d56) was characterized, in
      addition to hepatitis, by severe meningoencephalitis, associated with numerous
      brain cysts. Thus, the BGD1 strain of T. gondii has type II genotypic and
      immunologic characteristics, but unlike other type II strains of human origin,
      induces severe encephalitis, making it an alternative to the sheep-derived ME49
      strain for experimental models of infection.

PMID- 16797200
TI  - Immunogenicity and structural characterisation of an in vitro folded
      meningococcal siderophore receptor (FrpB, FetA).
AB  - The iron-limitation-inducible protein FrpB of Neisseria meningitidis is an outer
      membrane-localized siderophore receptor. Because of its abundance and its
      capacity to elicit bactericidal antibodies, it is considered a vaccine candidate.
      Bactericidal antibodies against FrpB are, however, type-specific. Hence, an FrpB
      based vaccine should comprise several FrpB variants to be capable of providing
      broad protection. To facilitate the development of a meningococcal subunit
      vaccine, we have established a procedure to obtain large quantities of the
      protein in a native-like conformation. The protein was expressed without its
      signal sequence in Escherichia coli, where it accumulated in inclusion bodies.
      After in vitro folding, the protein was biochemically, biophysically and
      biologically characterised. Our results show that in vitro folded FrpB assembles
      into oligomers, presumably dimers, and that it induces high levels of
      bactericidal antibodies in laboratory animals.

PMID- 16797201
TI  - Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus
      induced expression of antiviral cytokines.
AB  - Activation of host cell antiviral responses is mediated by pattern recognition
      receptors. Cytoplasmic RNA helicases, retinoic acid inducible gene-I (RIG-I) and
      melanoma differentiation-associated gene 5 (mda-5) have been identified to
      function as receptors for double-stranded RNA. Here we show that interferon (IFN)
      alpha pretreatment enhances influenza A virus-induced expression of IFN-alpha,
      IFN-beta, interleukin (IL)-28 and IL-29 genes in human dendritic cells and
      epithelial cell lines. Both IFN-alpha and IFN-beta strongly enhanced RIG-I and
      mda-5 mRNA and protein expression in these cell types. Expression of RIG-I and
      mda-5 gene constructs, but not that of TLR3, lead to a dramatic enhancement of
      IFN-beta promoter driven transcription in influenza A virus-infected epithelial
      cells. Furthermore, dominant negative RIG-I gene construct inhibited influenza A
      virus-induced IFN-beta promoter activity. In conclusion, our results show that in
      epithelial cells influenza A virus-induced antiviral cytokine gene expression is
      triggered by RIG-I and mda-5, whose expression is positively regulated by IFN
      alpha.

PMID- 16797202
TI  - Propionibacterium acnes and lipopolysaccharide induce the expression of
      antimicrobial peptides and proinflammatory cytokines/chemokines in human
      sebocytes.
AB  - Acne is a common skin disorder of the pilosebaceous unit. In addition to genetic,
      hormonal and environmental factors, abnormal colonization by Propionibacterium
      acnes has been implicated in the occurrence of acne via the induction of
      inflammatory mediators. To gain more insight into the role that sebocytes play in
      the innate immune response of the skin, particularly in acne, we compared the
      antimicrobial peptide and proinflammatory cytokine/chemokine expression at mRNA
      and protein levels, as well as the viability and differentiation of SZ95
      sebocytes in response to co-culture with representative isolates of P. acnes type
      IA and type IB as well as Escherichia coli-derived lipopolysaccharide (LPS). We
      found that, in vitro, P. acnes type IA and IB isolates and LPS induced human beta
      defensin-2 and proinflammatory cytokine/chemokine expression, and influenced
      sebocyte viability and differentiation. Our results provide evidence that
      sebocytes are capable of producing proinflammatory cytokines/chemokines and
      antimicrobial peptides, which may have a role in acne pathogenesis. Furthermore,
      since P. acnes types IA and IB differentially affect both the differentiation and
      viability of sebocytes, our data demonstrate that different strains of P. acnes
      vary in their capacity to stimulate an inflammatory response within the
      pilosebaceous follicle.

PMID- 16797203
TI  - Isolation and characteristics of sorbitol-fermenting Escherichia coli O157
      strains from cattle.
AB  - Cattle can be a reservoir of sorbitol-fermenting Escherichia coli O157 (SF E.
      coli O157) and a source of human diseases. In this study, six strains of SF E.
      coli O157 were isolated and characterized from cattle using an immunomagnetic
      separation procedure. PCR analysis of the SF E. coli O157 virulence markers
      showed that all six isolates tested positive for sfpA, rfbE and eaeA, and
      negative for terA, ureA, katP and espP. Two of the isolates contained the stx
      genes. Four isolates tested positive for enterohemorrhagic E. coli hlyA (EhlyA)
      by PCR but were nonhemolytic on the blood agar. Five isolates tested positive for
      the cdtA gene. The possession of these virulence factors was an indication of
      their pathogenic potential. The random amplified polymorphic DNA patterns, which
      were generated by the arbitrarily primed PCR of the SF E. coli O157 isolates from
      the cattle, were significantly different from those of the non-sorbitol
      fermenting E. coli O157 (NSF E. coli O157) strains originating from cattle or
      humans. GelCompar analysis showed that the SF E. coli O157 isolates had only a
      57% genetic similarity with the NSF E. coli strains. The minimal inhibitory
      concentration assay showed that imipenem inhibited the growth of the six isolates
      at a concentration of <4 microg/ml.

PMID- 16797204
TI  - Signature patterns revealed by microarray analyses of mice infected with
      influenza virus A and Streptococcus pneumoniae.
AB  - We used cDNA microarrays to identify differentially expressed genes in mice in
      response to infections with influenza virus A/PR/8/34 (H1N1) and Streptococcus
      pneumoniae. Expression microarray analysis showed up-regulation and down
      regulation of many genes involved in the defense, inflammatory response and
      intracellular signaling pathways including chemokine, apoptosis, MAPK, Notch, Jak
      STAT, T-cell receptor and complement and coagulation cascades. We have revealed
      signature patterns of gene expression in mice infected with two different classes
      of pathogens: influenza virus A and S. pneumoniae. Quantitative real-time RT-PCR
      results confirmed microarray results for most of the genes tested. These studies
      document clear differences in gene expression profiles between mice infected with
      influenza virus A and S. pneumoniae. Identification of genes that are
      differentially expressed after respiratory infections can provide insights into
      the mechanisms by which the host interacts with different pathogens, useful
      information about stage of diseases and selection of suitable targets for early
      diagnosis and treatments. The advantage of this novel approach is that the
      detection of pathogens is based on the differences in host gene expression
      profiles in response to different pathogens instead of detecting pathogens
      directly.

PMID- 16797205
TI  - Persistent joint swelling and Borrelia-specific antibodies in Borrelia garinii
      infected mice after eradication of vegetative spirochetes with antibiotic
      treatment.
AB  - We wanted to study the pathogenesis and the long-term manifestations of Borrelia
      garinii infection in SJL and C3H/He mice. We report here that B. garinii A218
      causes a persisting infection in these mouse strains. Mice infected with
      intracutaneous inoculation of B. garinii at 4-5 weeks of age developed a
      disseminated infection and joint swelling within 2 weeks of inoculation and
      remained infected with joint symptoms until the end of follow-ups of up to 52
      weeks. Treatment with ceftriaxone or ampicillin at 18 or 44 weeks of infection
      did not affect the joint swelling during the follow-ups of 19 and 8 weeks,
      respectively. However, B. garinii could not be cultured from any of the post
      mortem tissue samples of the treated mice, whereas the spirochete grew from
      samples of all untreated infected animals. Borrelia-specific IgG antibodies were
      detectable after 2 weeks of infection, and in late infection, all mice had high
      anti-borrelia IgG levels. Antibiotic treatment had no effect on antibody levels.
      Histology showed only slight changes in the joints of the infected mice with
      occasional lymphocyte infiltration, synovial proliferation and slight involvement
      of the Achilles' tendon. No difference was seen in the findings between
      ceftriaxone-treated and untreated mice. The results suggest that the presence of
      vegetative spirochetes is no prerequisite for persisting joint symptoms and
      elevated anti-borrelia IgG levels in these B. garinii-infected mice.

PMID- 16797206
TI  - Towards an immunodiagnostic test for leprosy.
AB  - In addition to multidrug therapy, elimination of leprosy requires improved
      diagnostic methods. Using a comparative genomics approach, 17 potential protein
      antigens (MLP) that are restricted to Mycobacterium leprae, or of limited
      distribution, were produced and tested for antigen-specific immune responses on
      leprosy patients, healthy contacts of leprosy patients, and tuberculosis patients
      in Mali and Bangladesh, as well as on non-endemic controls. T-cell antigenicity
      of MLP was confirmed by IFN-gamma production in whole-blood assays with the
      highest responses observed in paucibacillary leprosy patients and healthy
      contacts. Four MLP behaved well in both countries and induced significantly
      different responses between the study groups. Peptides carrying T cell epitopes
      from one of the antigens gave promising results in restimulation assays in mice
      and immune responses were not influenced by prior exposure to BCG or
      environmental mycobacteria. This study provides the immunological framework for
      the development of a specific, peptide-based immunodiagnostic test for leprosy.

PMID- 16797208
TI  - Interleukin-1 contributes to an effective clearance of Mycobacterium kansasii
      from the respiratory tract.
AB  - Mycobacterium kansasii is an emerging pathogen that is able to induce pulmonary
      disease resembling tuberculosis. To determine the role of interleukin (IL-)1 in
      lung infection caused by this atypical mycobacterium, IL-1 receptor type 1
      knockout (IL-1R(1) KO) and normal wild type mice were intranasally infected with
      M. kansasii. IL-1R(1) KO mice demonstrated a reduced antibacterial response in
      the lungs and an increased dissemination to the liver, which was accompanied by
      an enhanced pulmonary inflammatory response. These data identify IL-1 as an
      important component of the innate immune response to lung infection by M.
      kansasii.

PMID- 16797207
TI  - Immunogenicity of a recombinant protein containing the Plasmodium vivax vaccine
      candidate MSP1(19) and two human CD4+ T-cell epitopes administered to non-human
      primates (Callithrix jacchus jacchus).
AB  - One of the most promising vaccine candidates against the erythrocytic forms of
      malaria is the 19 kDa C-terminal region of the merozoite surface protein 1
      (MSP1(19)). As part of our studies aimed at the development of a Plasmodium vivax
      malaria vaccine, we characterized the immunogenic properties of a new bacterial
      recombinant protein containing the P. vivax MSP1(19) and two helper T-cell
      epitopes, the synthetic universal pan allelic DR epitope (PADRE) and a new
      internal MSP1 P. vivax epitope (DYDVVYLKPLAGMYK). We found that the recognition
      of His6MSP1(19)-DYDVVYLKPLAGMYK-PADRE was as good as the recognition of
      His6MSP1(19) indicating that the presence of the T-cell epitopes PADRE and
      DYDVVYLKPLAGMYK did not modify the MSP1(19) epitopes recognized by human IgG. The
      recombinant protein His6MSP1(19)-DYDVVYLKPLAGMYK-PADRE proved to be highly
      immunogenic in marmosets (Callithrix jacchus jacchus) when administered in
      incomplete Freund's adjuvant. However, when administered in other adjuvant
      formulations such as Quil A, CpG ODN 2006 or MPL/TDM, antibody titers to MSP1(19)
      were significantly lower. Among these three adjuvants, Quil A proved to be the
      most efficient one generating antibody titers significantly higher than the
      others. These results indicated that under the circumstances evaluated, adjuvants
      were key for the immunogenicity of the recombinant protein His6MSP1(19)
      DYDVVYLKPLAGMYK-PADRE.

PMID- 16797209
TI  - [Papillomavirus vaccines: dream or revolution?].

PMID- 16797210
TI  - Population data of nine STRs of Mexican-mestizos from Veracruz (Central South
      Eastern, Mexico).

PMID- 16797211
TI  - Y-linked haplotypes in Amerindian chromosomes from Mexican populations: genetic
      evidence to the dual origin of the Huichol tribe.
AB  - We studied six Y-linked short tandem repeats (Y-STRs) to describe the internal
      diversity of the Amerindian haplogroup Q-M3 in 129 males from eight Mexican
      populations. The low gene diversity in the Huichol tribe demonstrated the effects
      of genetic drift, attributable to geographic isolation and founder effect. The
      presence of two principal paternal lineages supported the historical and
      anthropometric records, which indicate that Huichols were formed by the fusion of
      two ancestral Mexican tribes. Moreover, genetic distances and close relationships
      of haplotypes between Huichols and Tarahumaras were in agreement with their
      linguistic affiliation. The high genetic diversity of the Purepechas and wide
      distribution of haplotypes along the constructed network-joining tree suggest
      that the present genetic composition was influenced by Purepecha dominance in
      western Mesoamerica. The Y-haplotypes shared between populations suggest that,
      among the Amerindian tribes studied herein, the paternal genetic pool of Nahuas
      could have contributed more importantly to the European-admixed population, the
      Mexican-Mestizos.

PMID- 16797212
TI  - Effects of drinking and smoking on endogenous levels of urinary gamma
      hydroxybutyric acid, a preliminary study.
AB  - The aim of this study was to determine if the endogenous levels of gamma
      hydroxybutyric acid (GHB) in urine were affected by drinking and smoking. Urine
      samples were obtained from 20 healthy volunteers (15 males, 21-45 years; 5
      females, 22-24 years). This population included four average drinkers (males), 4
      average smokers (males), and 12 nonsmokers/nondrinkers (seven males and five
      females). Urinary levels of GHB were measured by gas chromatography. No gender
      differences were observed in the urinary levels of endogenous GHB. The urinary
      levels of GHB in males were 0.52+/-0.37 microg/ml in smokers, 0.28+/-0.21
      microg/ml in nonsmokers/nondrinkers, and 0.23+/-0.04 microg/ml in drinkers.
      Urinary GHB levels were measured three times a day for 5 consecutive days in a
      male from each group. Large intra-individual differences were observed over the 5
      day period in a smoker and a nonsmoker/nondrinker. No significant changes in
      daily endogenous GHB levels were observed in a drinker during the period. Our
      preliminary results suggest that stimulatory effects of nicotine on the central
      nervous system (CNS) may result in an increase in nocturnal formation of GHB and
      the depressive effects of ethanol on the CNS may not affect, even may inhibit,
      nocturnal production of GHB.

PMID- 16797213
TI  - Relationship between pulmonary fat embolism and core body temperature in rats
      with a severe fatty liver.
AB  - We previously demonstrated that pulmonary fat embolism was induced by elevation
      of the core body temperature, in rats with a fatty liver. The aim of the present
      examination was to investigate the core body temperature at which pulmonary fat
      embolism developed capillaries through exposure to a high temperature, in rats
      with a fatty liver. Following heat stress, pulmonary fat embolism was observed to
      a slight degree at a core body temperature of 41 and 42 degrees C, whereas the
      severity of pulmonary fat embolism was greatly increased and was classified as
      severe at a core body temperature of 43 degrees C. Moreover, the concentrations
      of aspartate aminotransferase and alanine aminotransferase within plasma were
      significantly increased at a core body temperature of 43 degrees C. These results
      clearly indicate that the development of pulmonary fat embolism could be related
      to hyperthermia at above 42 degrees C following heat stress, and that fat emboli
      may be derived from the fatty liver itself. It is thus likely that pulmonary fat
      embolism can be considered as one form of evidence of hyperthermia in an
      individual with a fatty liver.

PMID- 16797214
TI  - Frequency and correlates of co-morbid psychosis and depression in Parkinson's
      disease.
AB  - Though both psychosis and depression are common in Parkinson's disease (PD), it
      is not clear if an association between the two disorders exists. One hundred and
      thirty PD patients were divided into four groups based on a comprehensive
      psychiatric assessment: (1) no depression or psychosis (47.7%); (2) psychosis
      only (16.2%); (3) depression only (26.2%); and (4) psychosis and depression
      (10.0%). Co-morbid psychosis and depression did not occur more frequently than
      expected by chance (P=.77). Psychosis was associated with dopamine agonist use
      (P=.02), depression with mild-cognitive impairment (P=.03), and their co
      occurrence with higher daily levodopa dosages (P<.01). These results suggest that
      psychosis and depression in PD are distinct neurobehavioral disorders.

PMID- 16797215
TI  - Parkinson's disease and family history.
AB  - The study of family history in Parkinson's disease (PD) has resulted in
      considerable debate over the role of genetic factors in the development of PD.
      Despite this, family history is consistently identified as an independent risk
      factor for PD. A multifactorial disease process in which genetic, environmental
      and lifestyle factors culminate in overall risk seems most likely. This article
      reviews existing studies of familial aggregation in PD. Recent insights into rare
      genetic causes of PD have affirmed the importance of ongoing family history
      research. Future efforts should emphasise well-designed family studies with
      extensive, non-exclusive phenotyping and ideally long-term follow-up.

PMID- 16797216
TI  - Participatory research in public health: creating innovative alliances for
      health.
AB  - This article discusses alliances within local socio-sanitary space, one in which
      community sector and health sector actors, public health researchers and funding
      bodies meet. The discussion is based on the study of a research space made up of
      representatives of actors found at the local level. Both the minutes of the
      discussions of 12 meetings of the research team, and the collaborative outputs
      produced throughout the research initiative provide the empirical data for a
      qualitative analysis. The findings reveal a research space concomitantly
      constituted by aspects of "non-cooperative games" and of networks based on
      innovation-fostering knowledge exchanges, which can be viewed, from the
      perspective of a reflexive epistemology, as a tool for implementing innovative
      alliances in local, health-promoting socio-sanitary space.

PMID- 16797217
TI  - Placing the dynamics of syringe exchange programs in the United States.
AB  - Drawing upon the broader health, social, and political geography literature, this
      paper outlines a framework for considering place-based processes through which
      syringe exchange availability may be understood. It is argued that the geographic
      distribution of syringe exchange programs (SEPs) in the United States is linked
      to the social and political conditions of particular localities through three
      place characteristics: (1) structural constraints; (2) social and spatial
      distancing of injection drug users; and (3) localized action. Although SEPs
      remain controversial and face ongoing obstacles from the government, law
      enforcement and local communities, they continue to operate through the efforts
      of grassroots organizations and local activists. Action on this issue occurs
      locally, and the characteristics of place-based factors affect whether particular
      areas adopt SEPs.

PMID- 16797218
TI  - Bone morphogenetic protein receptors and bone morphogenetic protein signaling are
      controlled by tumor necrosis factor-alpha in human bone cells.
AB  - Bone morphogenetic proteins (BMP) stimulate osteoblast differentiation by signal
      transduction via three BMP receptors (BMPR-IA, -IB and -II), whereas the
      inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been shown to
      suppress osteoblast differentiation. Although the mechanisms which regulate the
      BMPR are not yet known, it is possible that they may be negatively controlled by
      TNF-alpha, thereby inhibiting BMP-induced osteoblast differentiation. To test
      this hypothesis, we have examined the effects of TNF-alpha on BMPR-IA, -IB and 
      II expression and the functional consequences of this cytokine on BMPR-mediated
      functions in human bone cells. The results showed that although TNF-alpha down
      regulated BMPR-IA and -II transcripts, it increased the level of BMPR-IB mRNA via
      a MAPK-dependent pathway. In marked contrast, however, TNF-alpha nevertheless
      caused marked down-regulation of the expression of the BMPR-IB surface antigen
      specifically. Moreover, the cytokine-induced decrease in BMPR-IB expression was
      found to be associated with the concurrent presence of a 'soluble' form of this
      antigen in supernatants of TNF-alpha-treated cultures. Furthermore, the TNF-alpha
      induced loss of BMPR-IB was found to ablate BMP-2-stimulated bone cell functions,
      including phosphorylation of Smad1/5/8, alkaline phosphatase activity and
      osteocalcin expression. In conclusion, our study has provided evidence, for the
      first time, that BMPR can be differentially modulated by TNF-alpha at both the
      post-transcriptional and post-translational levels, with the TNF-alpha-induced
      shedding of the BMPR-IB antigen associated with a significantly diminished
      response to BMP-2 in vitro.

PMID- 16797219
TI  - Theory-based Bayesian models of inductive learning and reasoning.
AB  - Inductive inference allows humans to make powerful generalizations from sparse
      data when learning about word meanings, unobserved properties, causal
      relationships, and many other aspects of the world. Traditional accounts of
      induction emphasize either the power of statistical learning, or the importance
      of strong constraints from structured domain knowledge, intuitive theories or
      schemas. We argue that both components are necessary to explain the nature, use
      and acquisition of human knowledge, and we introduce a theory-based Bayesian
      framework for modeling inductive learning and reasoning as statistical inferences
      over structured knowledge representations.

PMID- 16797220
TI  - How good is your screening library?
AB  - Efficient library design is an ongoing challenge for investigators seeking novel
      ligands for proteins, whether for drug discovery or chemical biology. Strategies
      that add neglected chemistry or exclude unproductive compounds are two dominant
      recent themes, as is a growing awareness of molecular complexity and its
      implications. The choice of how complex molecules in screening libraries should
      be often amounts to how big they should be. Small, simple molecules have lower
      affinities and must be screened at high concentration, but they will also have
      higher hit rates. Larger compounds, on the other hand, will often more closely
      resemble final drugs, but because they are more highly functionalized and
      specific, they will have much lower hit rates. The best general-purpose screening
      libraries may well be those of intermediate complexity that are free of artifact
      causing nuisance compounds.

PMID- 16797221
TI  - Functional and immunological insights from the three-dimensional structures of
      Plasmodium surface proteins.
AB  - Malaria is a major global health problem and is caused by the unicellular
      parasite Plasmodium. Plasmodial surface proteins have important roles in host
      cell invasion and are responsible for antigenic diversity in this organism.
      Knowledge of the three-dimensional structure of surface proteins can facilitate
      our understanding their biological function, and contribute to the development of
      therapeutic and vaccine strategies against malaria. Structural studies allow
      rational drug design when ligand- or receptor-binding sites are identified and
      characterized. Analysis of the three-dimensional distribution of protective
      antibody epitopes and polymorphic residues can facilitate vaccine candidate
      optimization. With this in mind, some Plasmodium surface-protein structures have
      determined by X-ray crystallography or nuclear magnetic resonance.

PMID- 16797222
TI  - Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: Genotoxic
      effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated
      Chinese hamster ovary cells.
AB  - Zinc oxide (ZnO), a widely used ingredient in dermatological preparations and
      sunscreens, is clastogenic in vitro, but not in vivo. Given that ZnO has an
      approximately four-fold greater clastogenic potency in the presence of UV light
      when compared with that in the dark, it has been suggested to be photo
      clastogenic. In order to clarify whether this increased potency is a genuine
      photo-genotoxic effect, we investigated the clastogenicity of ZnO (mean particle
      size, 100 nm) in Chinese hamster ovary (CHO) cells in the dark (D), in pre
      irradiated (PI, i.e. UV irradiation of cells followed by treatment with ZnO) and
      in simultaneously irradiated (SI, i.e. ZnO treatment concurrent with UV
      irradiation) CHO cells at UV doses of 350 and 700 mJ/cm(2). The cytotoxicity of
      ZnO to CHO cells under the different irradiation conditions was as follows:
      SI>PI>D. In the dark, ZnO produced a concentration-related increase in chromosome
      aberrations (CA). In PI or SI CHO cells, ZnO was clastogenic at significantly
      lower concentrations (approximately two- to four-fold) when compared with
      effective concentrations in the dark, indicating an increased susceptibility of
      CHO cells to ZnO-mediated clastogenic effects due to UV irradiation per se. The
      incidence of CA in SI or PI cells was generally higher than that in the dark. At
      similar ZnO concentrations, SI conditions generally produced higher CA incidence
      than PI conditions. However, when ZnO concentrations producing similar
      cytotoxicity were compared, CA incidences under PI or SI conditions were nearly
      identical. The modest increase in the clastogenic potency of ZnO following UV
      irradiation contrasts with the results observed with genuine photo-clastogenic
      agents, such as 8-MOP, which may produce an increase in clastogenic potency of
      >15,000-fold under SI conditions. Our results provide evidence that, under
      conditions of in vitro photo-clastogenicity tests, UV irradiation of the cellular
      test system per se may produce a slight increase in the genotoxic potency of
      compounds that are clastogenic in the dark. In conclusion, our data suggest that
      minor increases in clastogenic potency under conditions of photo-genotoxicity
      testing do not necessarily represent a photo-genotoxic effect, but may occur due
      to an increased sensitivity of the test system subsequent to UV irradiation.

PMID- 16797223
TI  - Genotoxicity of acetaldehyde- and crotonaldehyde-induced 1,N2
      propanodeoxyguanosine DNA adducts in human cells.
AB  - Reaction of crotonaldehyde or two molecules of acetaldehyde with DNA generates 3
      (2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine
      10(3H)one (2, Scheme 1), which occurs in (6R, 8R) and (6S, 8S) configurations
      (Fig. 1). These diastereomers were site-specifically incorporated into
      oligonucleotides, which were then inserted into a double-stranded DNA vector for
      genotoxicity studies. Modified DNA was introduced into human xeroderma
      pigmentosum A (XPA) cells to allow replication. Analysis of progeny plasmid
      revealed that these DNA adducts inhibit DNA synthesis to similar degrees. (6S,
      8S)-2 miscodes more frequently than (6R, 8R)-2: 10% versus 5%. For both adducts,
      major miscoding events were G-->T transversions, but G-->A transitions were also
      observed at a comparable level for (6R, 8R)-2. G-->C transversions were the
      second most common events for (6S, 8S)-2. Comparison of these results with those
      of other 1,N2-propanodeoxyguanosine (PdG) adducts, which were evaluated by the
      same system, indicates that (i) their synthesis inhibiting potencies are stronger
      than that of the unsubstituted analog, 3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro
      8-hydroxypyrimido[1,2-a]purine-10(3H)one (1, Scheme 1), but weaker than that of 3
      (2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-6-hydroxypyrimido[1,2-a]purine-10(3H)one
      (3, Scheme 1); (ii) both isomers of 2 are more miscoding than 1; (iii) the
      miscoding potency of (6S, 8S)-2 is comparable to those of 3 and a model PdG 4
      lacking a hydroxyl and a methyl group (Fig. 1). Therefore, considering the fact
      that 2 are formed endogenously as well as exogenously, they may play a
      significant role in aging and cancer in humans.

PMID- 16797224
TI  - SFTG international collaborative study on in vitro micronucleus test III. Using
      CHO cells.
AB  - In this report, results are presented from an international study of the in vitro
      micronucleus assay using Chinese hamster ovary cells. This study was coordinated
      by an organizing committee supported by the SFTG (the French branch of the
      European Environmental Mutagen Society). Test chemicals included mannitol,
      bleomycin, cytosine arabinoside, urethane and diethylstilboestrol. Mitomycin C
      was used as a positive control. Each chemical was evaluated in at least two
      laboratories following a variety of different protocols (short and long
      exposures, varying recovery times, with and without cytochalasin B) in order to
      help determine a standard protocol for routine testing in Chinese hamster ovary
      cells. Mannitol and urethane were negative, while bleomycin, cytosine arabinoside
      and diethylstilboestrol induced a dose dependent increase in micronucleated
      cells. In the presence of cytochalasin B, increases in micronuclei were observed
      in binucleated as well as mononucleated cells in cultures treated with bleomycin,
      cytosine arabinoside or diethylstilboestrol. Importantly, all three of these
      chemicals were detected in each of the different treatment/recovery regimens. No
      differences were seen in the sensitivity or accuracy of the responses in the
      presence of absence of cytochalasin B. Overall, these results demonstrate the
      suitability of Chinese hamster ovary cells for the in vitro micronucleus assay.

PMID- 16797225
TI  - SFTG international collaborative study on in vitro micronucleus test V. Using
      L5178Y cells.
AB  - In this report, results are presented from an international study of the in vitro
      micronucleus assay using mouse lymphoma L5178Y cells. This study was coordinated
      by an organizing committee supported by the SFTG (the French branch of the
      European Environmental Mutagen Society). Test chemicals included mannitol,
      bleomycin, 5-fluorouracil, colchicine and griseofulvin. Mitomycin C was used as a
      positive control. Each chemical was evaluated in at least two laboratories
      following a variety of different protocols (short and long exposures, varying
      recovery times, with and without cytochalasin B) in order to help determine a
      standard protocol for routine testing in mouse lymphoma L5178Y cells. Mannitol
      was the only exception, being tested in only one laboratory. Mannitol was
      negative, while bleomycin induced a concentration-dependent increase in
      micronucleated cells. Equivocal results were obtained for 5-fluorouracil,
      colchicine and griseofulvin. High levels of cytotoxicity interfered with the
      assessment of aneuploidy for colchicine and griseofulvin, preventing the ability
      to obtain clear results in all the treatment schedules. Experiments with 5
      fluorouracil, colchicine and griseofulvin showed that both short and long
      treatment times are required as each compound was detected using one or more
      treatment protocol. No clear differences were seen in the sensitivity or accuracy
      of the responses in the presence of absence of cytochalasin B. It was also found
      that a recovery period may help to detect compounds which induce a genotoxicity
      associated to a reduction in cell number or cell proliferation. Overall, the
      results of the present study show that mouse lymphoma L5178Y cells are suitable
      for the in vitro micronucleus assay.

PMID- 16797226
TI  - Induction of LacZ mutations in Muta Mouse can distinguish carcinogenic from non
      carcinogenic analogues of diaminotoluenes and nitronaphthalenes.
AB  - 2,4-Diaminotoluene (2,4-DAT) is a liver carcinogen in rats and mice whereas 2,6
      DAT is not. Both are genotoxic in vitro. Tests for mutations in transgenic mice,
      unscheduled DNA synthesis (UDS), DNA damage and enhancement of initiated foci in
      vivo have shown some discrimination between these two analogues, but only after
      oral administration. 1- and 2-nitronaphthalene (1- and 2-NNT) are also both
      genotoxic in vitro, although, unlike 2,4- and 2,6-DAT, they do not require
      metabolic activation. There is some evidence that 2-NNT may be able to induce
      liver and bladder tumours, and there is some evidence that 1-NNT is not
      carcinogenic to rats or mice, but none of the data are convincing. When tested
      for induction of LacZ mutations in Muta Mouse after topical exposure (human
      occupational exposure route) at their maximum tolerated doses, 2,4-DAT induced a
      positive response in liver and a marginal response in kidney, whereas 2,6-DAT was
      negative. 2-NNT also induced a positive mutagenic response in liver, and a
      marginal response in bladder, whereas 1-NNT was negative. Neither 2,4- nor 2,6
      DAT induced mutations at the site of application (skin) as might be expected for
      chemicals requiring activation by liver enzymes. 2-NNT, which is a direct-acting
      mutagen in vitro, gave a marginal response for induced mutation at the site of
      application, but 1-NNT was negative. This study shows that investigation of
      induction of LacZ mutations after topical application in vivo can provide useful
      data to help discriminate potentially carcinogenic from non-carcinogenic
      chemicals that are mutagenic in vitro. Robust carcinogenicity data are needed to
      determine whether 2-NNT can induce tumours in the liver and bladder.

PMID- 16797227
TI  - Building an ontology of pulmonary diseases with natural language processing tools
      using textual corpora.
AB  - Pathologies and acts are classified in thesauri to help physicians to code their
      activity. In practice, the use of thesauri is not sufficient to reduce
      variability in coding and thesauri are not suitable for computer processing. We
      think the automation of the coding task requires a conceptual modeling of medical
      items: an ontology. Our task is to help lung specialists code acts and diagnoses
      with software that represents medical knowledge of this concerned specialty by an
      ontology. The objective of the reported work was to build an ontology of
      pulmonary diseases dedicated to the coding process. To carry out this objective,
      we develop a precise methodological process for the knowledge engineer in order
      to build various types of medical ontologies. This process is based on the need
      to express precisely in natural language the meaning of each concept using
      differential semantics principles. A differential ontology is a hierarchy of
      concepts and relationships organized according to their similarities and
      differences. Our main research hypothesis is to apply natural language processing
      tools to corpora to develop the resources needed to build the ontology. We
      consider two corpora, one composed of patient discharge summaries and the other
      being a teaching book. We propose to combine two approaches to enrich the
      ontology building: (i) a method which consists of building terminological
      resources through distributional analysis and (ii) a method based on the
      observation of corpus sequences in order to reveal semantic relationships. Our
      ontology currently includes 1550 concepts and the software implementing the
      coding process is still under development. Results show that the proposed
      approach is operational and indicates that the combination of these methods and
      the comparison of the resulting terminological structures give interesting clues
      to a knowledge engineer for the building of an ontology.

PMID- 16797228
TI  - Does quantification of virus transcription provide a real measure of parvovirus
      B19 infectivity?

PMID- 16797229
TI  - Dengue fever with papilledema: a case of dengue-3 virus infection in central
      nervous system.
AB  - BACKGROUND AND OBJECTIVES: Neurological manifestations of dengue fever are rarely
      reported during acute illness and clinical presentation commonly observed is of
      acute encephalitis or one of the post-infectious immune mediated manifestations.
      We describe a case of dengue fever having mild encephalopathy and papilledema at
      presentation. CASE REPORT: Twenty-year-old female presented with fever, headache
      and vomiting. On examination she did not have classical signs of dengue fever and
      was found to have bilateral papilledema on fundus examination. Detailed work-up
      did not reveal any other cause of papilledema. Diagnosis of dengue fever was
      established by blood IgM antibody test on day 7 of illness. Retrospective
      analysis of CSF (drawn on day 5 of illness) by RT-PCR assay showed a
      characteristic band of dengue-3 virus. Papilledema was transient and subsided
      following symptomatic treatment. The patient recovered from acute illness and
      follow-up was unremarkable. CONCLUSION: Especially in dengue endemic areas, in
      the patients having acute febrile illness with subtle signs and symptoms
      suggestive of CNS involvement, dengue virus infection should also be ruled out
      early in the clinical course.

PMID- 16797230
TI  - Effects of theta burst stimulation protocols on phosphene threshold.
AB  - OBJECTIVE: We investigated the effects on occipital cortex, of two newly
      developed methods of repetitive transcranial magnetic stimulation (rTMS):
      continuous and intermittent theta burst stimulation (cTBS and iTBS), that lead to
      long lasting changes in excitability when applied over primary motor cortex.
      METHODS: Phosphene threshold to a single TMS pulse was measured before and after
      application of either continuous or intermittent theta burst stimulation
      (cTBS/iTBS; 600 total pulses at 80% phosphene threshold). RESULTS: In our cohort,
      cTBS increased phosphene threshold by an average of 10%. In contrast, iTBS, which
      transiently increases motor cortex excitability, had no effect on phosphene
      threshold. CONCLUSIONS: cTBS can be applied successfully to non-motor areas of
      cortex, but iTBS may need modification to produce maximal effects. SIGNIFICANCE:
      cTBS maybe a new useful tool in disorders characterized by an abnormal state of
      activity of the visual cortex.

PMID- 16797231
TI  - Artificial neural network: a new diagnostic posturographic tool for disorders of
      stance.
AB  - OBJECTIVE: To determine the accuracy of diagnoses made with artificial neural
      network techniques (ANNW) that identify postural sway patterns typical for
      balance disorders. METHODS: Body sway was measured by means of posturography
      during 10 test conditions of increasing difficulty. From a database of 676
      subjects 60 training cases (TCs) and 60 validation cases (VCs) were selected in
      which the following diagnoses had been established clinically: normal subject
      (NS), postural phobic vertigo (PPV), anterior lobe cerebellar atrophy (CA),
      primary orthostatic tremor (OT), and acute unilateral vestibular neuritis (VN). A
      standard 3-layer feed-forward ANNW, using the backpropagation algorithm, was
      trained with TCs, validated with VCs, and its accuracy tested on 5 new cases.
      RESULTS: ANNW differentiated the established diagnoses with an overall
      sensitivity and specificity of 0.93. Sensitivity and specificity were 1 for NS
      and OT; for PPV, 0.87 and 0.96; for CA, 1 and 0.98; and for VN, 0.8 and 0.98,
      respectively. New subjects were identified with ANNW output variables of the true
      diagnoses between 0.73 and 1. CONCLUSIONS: ANNW differentiates postural sway
      patterns of several distinct clinical balance disorders with high sensitivity and
      specificity. Once designed and tested ANNW could be considered a black box, which
      each examiner can apply to predict a specific diagnosis even without a clinical
      examination. SIGNIFICANCE: A promising diagnostic tool for disorders of upright
      stance in selected neurological disorders.

PMID- 16797232
TI  - Transcranial magnetic stimulation and cortical evoked potentials: a TMS/EEG co
      registration study.
AB  - OBJECTIVE: In recent years, a promising tool has been introduced which allows the
      co-registration of electroencephalographic (EEG) activity during brain
      transcranial magnetic stimulation (TMS). The aims of the present study are to
      identify eventual stimulus-related artefacts, and to confirm and extend previous
      EEG/TMS findings about the possible networks generating EEG responses evoked by
      TMS. METHODS: Focal TMS was delivered to the left primary motor cortex (MI), with
      different coils (real and sham) and orientations (45 and 135 degrees in respect
      to the sagittal plane), in six healthy subjects. EEG and motor evoked potentials
      (MEPs) were simultaneously recorded from 19 scalp electrodes. RESULTS: TMS, with
      coil oriented at 45 degrees , induced EEG responses characterized by a sequence
      of positive deflections peaking at approximately 14, 30, 60 and 190 ms and
      negative deflections peaking at approximately 10, 18, 40 and 100 ms post-TMS. The
      negative components were recorded at the recording electrode corresponding with
      the stimulation site (N10, N18), as well as at recording electrodes over the
      frontal region of the contralateral, unstimulated, hemisphere (N40) and
      bilaterally over the central hemispheres with its maximal representation at the
      stimulation site (N100). The positive components were instead detected at the
      frontal region of the right, unstimulated, hemisphere (P14), over the central
      electrodes Cz, Fz and the frontal region of the right hemisphere (P30), at the
      stimulation site (P60), and over the frontal regions of both hemispheres. When
      TMS was delivered with the coil oriented at 135 degrees , no MEPs were recorded
      from the right target muscle. Nonetheless, all the TMS-induced EEG components
      were still evoked apart from the N20-P30. Finally, TMS with the sham coil over
      left MI did not induce either significant EEG responses or MEPs. CONCLUSIONS: In
      conclusion, the TMS evoked components we have obtained by recording in continuous
      mode strikingly fit with those already described by other authors for both their
      latencies and the spatio-temporal pattern of scalp distribution. SIGNIFICANCE:
      This experiment is a farther validation of the combined EEG/TMS recording
      technique as a promising tool for experimental and clinical purposes.

PMID- 16797233
TI  - Cardiovascular responses during recreational 5-a-side indoor-soccer.
AB  - The aims of this study were to examine the cardiovascular response to
      recreational 5-a-side indoor-soccer (5v5) matches (5v5 study, 5v5S, n=15) and to
      assess the validity of using heart rate (HR) to estimate oxygen uptake (VO(2))
      demands during actual game-play (validity study, VS, n=16) in young subjects (age
      16.8+/-1.5 years). Game responses during 5v5S were assessed during 30 min matches
      using short-range telemetry heart-rate monitors. In VS games (12 min), VO(2) and
      HR were monitored with a portable gas analyser (K4b(2), COSMED, Rome, Italy).
      Individual HR-VO(2) relationships were determined from a laboratory treadmill run
      to exhaustion (VS) and a multistage shuttle running fitness test (5v5S) using
      K4b(2). Results showed that 5v5 elicits 83.5+/-5.4 and 75.3+/-11.2% of HR(peak)
      and VO(2peak), respectively. Ninety-one percent of the playing time (30 min) was
      spent at HR higher than 70% of HR(peak). In VS match, gas analyses revealed that
      only 71% of HR variance was explained by VO(2) variations. However, playing at
      approximately 70% of HR(peak) elicited 51.6+/-11.2% of VO(2peak). Group actual
      versus predicted VO(2) values demonstrated no significant differences (p>0.05),
      however, large confidence limits were observed (+6.20 and -10.53 mlkg(-1)min(
      1)). These results show that HR and VO(2) responses to recreational 5v5 soccer in
      young athletes are similar to the exercise intensities recommended by ACSM for
      promoting cardiovascular health and suggest that HR is valid to prescribe and
      monitor aerobic intermittent exercise. These results also show that HR measures
      are acceptable for estimating VO(2) during intermittent exercise when assessing
      large groups, but show that large estimation errors can occur at the individual
      level.

PMID- 16797235
TI  - The role of residential location in apparent helminth and malaria associations.
AB  - Conflicting opinions on the nature of malaria and helminth coinfections in humans
      have highlighted the need for a rational approach to study the effects of
      coinfections on morbidity. Here, it is argued that a variety of factors have led
      to this confusion but that many problems might be helped by more deliberate
      consideration of residential location and spatial aspects of exposure in
      parasitological surveys.

PMID- 16797234
TI  - Transmission and immunity: the importance of heterogeneity in the fight against
      malaria.
AB  - The complex relationship between transmission and parasite prevalence in humans
      is an important issue. Using a large dataset matching estimates of malaria
      transmission and Plasmodium falciparum prevalence in African children, a
      stimulating study published in Nature provides evidence that heterogeneity in
      susceptibility crucially determines the prevalence of infection. Moreover, it
      suggests that children who clear infections are not immune to new infections,
      irrespective of the amount of transmission. It is important to question the
      relevance of such results based on mathematical models when discussing host
      parasite interactions, especially their implications for public health
      interventions.

PMID- 16797236
TI  - PTreeRec: Phylogenetic Tree Reconstruction based on genome BLAST distance.
AB  - Phylogenetic Tree Reconstruction (PTreeRec) is a web-based tool for automatic
      phylogeny inferences from whole-genome sequences, which accepts files of DNA
      sequences in the FASTA format and allows users to save the output tree file, and
      displays the inferred tree through an applet in a web browser. PTreeRec involves
      three basic steps. First, regions of maximal segment pairs (MSPs) based on an all
      against-all pairwise comparison of genomes are located. Second, a distance matrix
      is calculated from MSP scores or coverage. Finally, a phylogenetic tree is
      reconstructed by the neighbor-joining method.

PMID- 16797237
TI  - CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells.
AB  - We previously reported that 4C8 monoclonal antibody (mAb) provides a
      costimulatory signal to human CD4+ T cells and consequently induces regulatory T
      (Treg) cells, which are hypo-responsive and suppress the polyclonal response of
      bystander CD4+ cells in a contact-dependent manner. In this study, we identified
      the antigen of 4C8 mAb as CD52. Costimulation with Campath-1H, a humanized anti
      CD52 mAb, also induced Treg cells. Anti-CD52-induced Treg cells suppressed the
      proliferation of both CD4+ and CD8+ T cells provided with polyclonal or
      allogeneic stimulation. When Treg cells were induced from Staphylococcal
      enterotoxin B (SEB) treated cells, they suppressed the response to SEB more
      efficiently than that to another superantigen, SEA. Furthermore, anti-CD52
      induced Treg cells could be expanded by culture with IL-2 followed by CD52
      costimulation, and co-injection of expanded Treg cells suppressed lethal
      xenogeneic graft versus host disease (GvHD) reactions in SCID mice caused by
      human peripheral blood mononuclear cells (PBMCs).

PMID- 16797238
TI  - A chimpanzee-origin adenovirus vector expressing the rabies virus glycoprotein as
      an oral vaccine against inhalation infection with rabies virus.
AB  - Rabies has the highest fatality rate of all human viral infections and the virus
      could potentially be disseminated through aerosols. Currently licensed vaccines
      to rabies virus are highly effective but it is unknown if they would provide
      reliable protection to rabies virus transmitted through inhalation, which allows
      rapid access to the central nervous system upon entering olfactory nerve endings.
      Here we describe preclinical data with a novel vaccine to rabies virus based on a
      recombinant replication-defective chimpanzee-origin adenovirus vector expressing
      the glycoprotein of the Evelyn Rokitniki Abelseth strain of rabies virus. This
      vaccine, termed AdC68rab.gp, induces sustained central and mucosal antibody
      responses to rabies virus after oral application and provides complete protection
      against rabies virus acquired through inhalation even if given at a moderate
      dose.

PMID- 16797239
TI  - The European Association of Echocardiography - and the future of European
      echocardiography.

PMID- 16797240
TI  - Esomeprazole with aspirin versus clopidogrel for prevention of recurrent
      gastrointestinal ulcer complications.
AB  - BACKGROUND AND AIMS: The role of clopidogrel in patients at risk for
      gastrointestinal complications is uncertain, although it has been recommended for
      patients who have gastrointestinal intolerance to aspirin. We tested the
      hypothesis that clopidogrel is as effective as esomeprazole and aspirin in
      preventing recurrences of ulcer complications. METHODS: This was a prospective,
      double-blind, randomized, controlled study of 170 patients who developed ulcer
      bleeding after the use of low-dose aspirin between November 2002 and January
      2005. After healing of ulcers and eradication of Helicobacter pylori, if present,
      patients were assigned randomly to treatment with esomeprazole 20 mg/day and
      aspirin 100 mg/day (n = 86) or clopidogrel 75 mg/day (n = 84) for 52 weeks. The
      primary end point was recurrent ulcer complications. RESULTS: During a median
      follow-up period of 52 weeks, no patient in the esomeprazole group, as compared
      with 9 patients in the clopidogrel group, developed recurrent ulcer
      complications. The cumulative incidences of recurrent ulcer complications were 0%
      in patients receiving esomeprazole and aspirin and 13.6% in patients receiving
      clopidogrel (absolute difference, 13.6%; 95% confidence interval for the
      difference, 6.3-20.9; log-rank test, P = .0019). CONCLUSIONS: The combination of
      esomeprazole and aspirin is superior to clopidogrel in preventing ulcer
      complications in patients who have a past history of aspirin-related peptic ulcer
      bleeding.

PMID- 16797241
TI  - Severe hepatic side effects of ezetimibe.
AB  - BACKGROUND AND AIMS: Ezetimibe was introduced recently as a new class of
      cholesterol-lowering drugs. Until now only limited increases of transaminase
      levels were reported. METHODS: We studied 2 patients with severe hepatic side
      effects of ezetimibe in a general community hospital. RESULTS: Ezetimibe may lead
      to 2 distinct types of severe hepatic side effects. CONCLUSIONS: Ezetimibe may
      rarely cause hepatotoxicity, severe cholestatic hepatitis, or acute autoimmune
      hepatitis.

PMID- 16797242
TI  - Genetics of colonic polyposis.

PMID- 16797243
TI  - Clinical, radiologic, and manometric characteristics of chronic intestinal
      dysmotility: the Stanford experience.
AB  - BACKGROUND AND AIMS: The clinical spectrum of chronic intestinal dysmotility
      (CID) is not well known. We determined the spectrum of motor abnormalities,
      underlying pathology, clinical course, and response to treatment of adults with
      CID at a tertiary referral center. METHODS: This was a descriptive retrospective
      analysis of a CID cohort conducted at a tertiary referral gastrointestinal (GI)
      motility center. A total of 113 referred patients underwent gastroduodenal
      manometry, other motility studies as appropriate, and radiologic and/or
      endoscopic assessment to exclude mechanical intestinal obstruction. RESULTS:
      Common symptoms included abdominal distention, abdominal pain, nausea, and
      constipation. The course was chronic with intermittent symptoms. Gastroduodenal
      manometry was abnormal in all patients; a pattern suggestive of a neuropathic
      process was the most common. Other GI motility studies showed delayed gastric,
      gallbladder, and colonic transit, nonspecific esophageal dysmotility, sphincter
      of Oddi hypertonicity, and poor rectal balloon sensation/expulsion. Treatment
      involved nutritional support, prokinetics, analgesics, antinausea agents, and
      laxatives, with variable response and high morbidity, multiple emergency
      admissions, need for nutritional support, and poor response to surgery. Nearly
      40% of the patients underwent abdominal surgery. CONCLUSIONS: Patients with CID
      have a chronic course and high morbidity. Because any segment of the GI tract may
      be involved in CID, functional assessment of the entire GI tract is recommended.
      CID presents several unmet clinical needs even in tertiary centers with
      expertise.

PMID- 16797244
TI  - Liver diseases in the hemochromatosis and iron overload screening study.
AB  - BACKGROUND AND AIMS: The Hemochromatosis and Iron Overload Screening (HEIRS)
      Study screened 101,168 primary care participants for iron overload with serum
      transferrin saturation (TS), ferritin, and C282Y and H63D mutations of the HFE
      gene. METHODS: All C282Y homozygotes and participants with an increased TS (>45%
      women, >50% men) and serum ferritin level (> 200 microg/L women, >300 microg/L
      men) were recalled for a clinical history and physical examination, and blood
      tests including alanine transaminase (ALT) and aspartate transaminase levels.
      Hepatitis B surface antigen and anti-hepatitis C virus were measured if the ALT
      level was increased (>31 IU/L in women, >40 IU/L in men). RESULTS: In the group
      of participants selected to return for clinical examination because of increased
      TS and ferritin levels, ALT increases and anti-hepatitis C virus were found in 95
      of 284 (33%) African Americans, 50 of 466 (11%) Asian and Pacific Islanders, 21
      of 120 (18%) Hispanics, and 40 of 477 (8.4%) Caucasians. ALT increases and
      hepatitis B surface antigen were detected in 24 of 466 (5%) Asian and Pacific
      Islanders, 10 of 284 (3.5%) African Americans, 3 of 120 (2.5%) Hispanics, and 2
      of 477 (.42%) Caucasians. Of 86 liver biopsy specimens obtained for clinical
      purposes, 53 were reviewed by a single study pathologist. Liver fibrosis (stage 3
      or 4) was present in 2 of 11 (18.2%) C282Y homozygotes that underwent central
      review and 2 of 302 (.66%) C282Y homozygotes attending the clinical examination.
      CONCLUSIONS: Screening for iron overload with ferritin and TS detects persons
      with viral hepatitis and other types of liver disease. A minimum of .66% C282Y
      homozygotes have liver fibrosis.

PMID- 16797246
TI  - The AmpliChip CYP450 test: principles, challenges, and future clinical utility in
      digestive disease.
AB  - Understanding genetically encoded inherited differences in drug metabolism and
      targets (ie, receptors, transporters) offers the promise of minimizing adverse
      drug reactions and improving therapies. Among the enzymes involved in drug
      metabolism, the cytochromes P450 (CYP450) hold a central position. In fact,
      CYP450 are involved in the biotransformation of most drugs used in clinical
      practice. Recent advances in the development of DNA-based diagnostics, coupled
      with a better understanding of genetic polymorphisms in influencing pharmacologic
      responses, have provided the foundation for novel in vitro tests that may predict
      side effects and/or therapeutic responses. The AmpliChip CYP450 test was
      developed as a clinical test to evaluate an individual's metabolic capacity for
      certain drugs by identifying polymorphisms of 2 CYP450 enzymes (ie, CYP2D6 and
      CYP2D19). Even though the AmpliChip CYP450 has been approved by the US Food and
      Drug Administration, its practical clinical utility has not yet been determined,
      and there is a paucity of data related to gastrointestinal and liver diseases. An
      understanding of the principles and opportunities provided by this new category
      of diagnostic test is key before planning the necessary studies to evaluate the
      usefulness of AmpliChip CYP450 in gastroenterologic clinical practice.

PMID- 16797245
TI  - Case report: fulminant hepatic failure involving duloxetine hydrochloride.
AB  - BACKGROUND AND AIMS: Duloxetine hydrochloride was approved by the Food and Drug
      Administration in August 2004 for the treatment of major depressive disorder and
      diabetic peripheral neuropathic pain. Initial product labeling contained a
      precaution regarding the risk for increases in liver function test results.
      Recently, postmarketing research has revealed episodes of cholestatic jaundice
      and increases in transaminase levels to greater than 20 times normal in patients
      with chronic liver disease. METHODS: In this case report, we describe a patient
      with non-Hodgkin's lymphoma in remission and depression treated with duloxetine
      and mirtazapine. RESULTS: Approximately 6 weeks after increasing her duloxetine
      dose from 30 to 60 mg daily, she became jaundiced and presented with fulminant
      hepatic failure. Liver function tests immediately before initiating duloxetine
      were not available, although the patient carried no prior history of chronic
      liver disease. A complete work-up for alternate causes failed to reveal another
      explanation for the patient's clinical presentation. A liver biopsy examination
      showed histologic changes of subacute injury and the patient's clinical course
      was consistent with drug-induced liver injury. Despite aggressive measures, the
      patient's condition deteriorated and the decision was made to withdraw care.
      CONCLUSIONS: This report shows a case of fulminant hepatic failure and death
      involving duloxetine use. Given recent reports of severe hepatotoxicity
      associated with the use of duloxetine in patients with pre-existing liver
      disease, further investigation into the safety of this compound is warranted.

PMID- 16797247
TI  - Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti
      inflammatory drugs in colorectal cancer prevention.
AB  - BACKGROUND AND AIMS: Variant genotypes of uridine diphosphate
      glucuronsyltransferase isoenzyme 1A6 (UGT1A6) associated with decreased metabolic
      activity have been associated with an enhanced protective effect of aspirin on
      the development of colorectal adenomas. However, interactions between UGT1A6
      variants or variants of another enzyme that metabolizes nonsteroidal anti
      inflammatory drugs (NSAIDs), cytochrome P4502C9 (CYP2C9), and NSAIDs in the
      prevention of colorectal cancer have not been studied extensively. METHODS:
      UGT1A6 and CYP2C9 genotypes were determined in 2295 individuals with colorectal
      cancer and 2903 controls. Interactions between these genotypes, aspirin or
      ibuprofen use, and colorectal cancer risk were determined. RESULTS: Variant
      CYP2C9 genotypes enhanced the protective effect of ibuprofen on the prevention of
      colorectal cancer, and a dose-response relationship with respect to increasing
      numbers of variant alleles was seen (P interaction = .02). CYP2C9 variants were
      more effective in individuals with wild-type rather than variant UGT1A6 (P
      interaction < .007). Variant CYP2C9 genotypes showed no interaction with aspirin
      usage, and variant UGT1A6 genotypes showed no interaction with either NSAID with
      respect to colorectal cancer protection. CONCLUSIONS: In this study, the major
      effect seen was an enhancement by slower-metabolizing CYP2C9 variants of the
      chemopreventive activity of ibuprofen against colorectal cancer.

PMID- 16797248
TI  - Abnormalities of serotonin metabolism and their relation to symptoms in untreated
      celiac disease.
AB  - BACKGROUND AND AIMS: Serotonin (5-hydroxytryptamine [5-HT]) is a key modulator of
      gut function that in excess causes nausea, vomiting, and diarrhea. We recently
      showed that patients with post-infective irritable bowel syndrome have increased
      postprandial release of 5-HT associated with low-grade T-cell mediated
      inflammation. Celiac disease is another common disease in which a T-cell
      enteropathy is associated with increased mucosal 5-HT levels. Our aim was to
      determine how this inflammatory lesion influenced 5-HT bioavailability and how
      changes in 5-HT related to the symptoms of nausea, vomiting, and diarrhea seen in
      untreated celiac patients. METHODS: Fasting plasma and platelet 5-HT and
      postprandial plasma 5-HT levels were measured after a high-carbohydrate meal in
      celiac patients (n = 18) and healthy controls (n = 18) using high-pressure liquid
      chromatography. Dyspepsia was assessed during the postprandial period using a
      questionnaire. Finally, we compared the histology and mucosal 5-HT levels in
      duodenal biopsy specimens from celiac patients and controls. RESULTS: Celiac
      patients had increased 5-HT-containing enterochromaffin cell numbers and
      significantly higher peak plasma 5-HT levels (P = .0002), postprandial area under
      the curve (P = .0006), and platelet 5-HT stores (P = .031) than controls. Peak 5
      HT levels correlated significantly with postprandial dyspepsia scores (P = .005).
      Celiac patients had higher duodenal 5-HT levels (P = .007) than controls.
      CONCLUSIONS: Celiac disease is associated with increased mucosal 5-HT content and
      enhanced 5-HT release from the upper small bowel, which correlates with
      postprandial dyspepsia. Serotonin excess may mediate dyspeptic symptoms in
      untreated celiac disease.

PMID- 16797249
TI  - Onercept for moderate-to-severe Crohn's disease: a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND AND AIMS: Onercept is a recombinant, soluble human p55 receptor to
      tumor necrosis factor-alpha. METHODS: A randomized, double-blind, placebo
      controlled, dose-ranging trial was performed to evaluate the efficacy of onercept
      induction therapy in patients with Crohn's disease (CD). Patients (n = 207) with
      moderate-to-severe acute or chronic active CD were randomized to receive
      subcutaneous onercept (10, 25, 35, or 50 mg) or placebo 3 times weekly for 8
      weeks. Primary analysis was induction of remission (defined as a CD activity
      index score < or = 150) at week 8. RESULTS: A total of 104 patients had acute
      active CD. Remission rates at week 8 were 23.5% for placebo (n = 17), and 34.8%,
      20.0%, 26.1%, and 28.6% for onercept 10 mg (n = 23), 25 mg (n = 20), 35 mg (n =
      23), and 50 mg (n = 21), respectively (P = .98). A total of 103 patients had
      chronic active CD. Remission rates at week 8 were 23.8% for placebo (n = 21), and
      23.8%, 9.1%, 35.3%, and 13.6% for onercept 10 mg (n = 21), 25 mg (n = 22), 35 mg
      (n = 17), and 50 mg (n = 22), respectively (P = .66). There were no differences
      between treatment groups in the incidence of adverse events. However, mild-to
      moderate injection-site reactions occurred in up to 12% of onercept-treated
      patients. CONCLUSIONS: Onercept was well tolerated but was not effective at the
      doses studied in patients with active CD.

PMID- 16797250
TI  - Advances in chemotherapy for colorectal cancer.
AB  - Gastroenterologists have a primary role in the management of colorectal cancer
      patients in that they frequently establish the diagnosis, direct or perform tumor
      staging evaluations, and initiate referrals for oncologic treatment. Several
      important advances have been made in the adjuvant treatment of colon and rectal
      cancers and in therapy of metastatic disease. These advances include the
      development of more effective combination chemotherapy regimens and molecularly
      targeted antibodies. These antibodies are directed against regulators of
      angiogenesis (vascular endothelial growth factor) and tumor cell growth
      (epidermal growth factor receptor) and have been shown to enhance the efficacy of
      cytotoxic chemotherapy. In the treatment of localized rectal cancer, the
      integration of chemotherapy and radiation with surgery has resulted in
      neoadjuvant approaches that achieve improved tumor control, sphincter
      preservation, and reduce treatment-related toxicities. This review presents an
      update of the current approach to colon and rectal cancer treatment, highlighting
      recent chemotherapeutic advances in the management of these highly prevalent
      malignancies.

PMID- 16797251
TI  - A prospective study of complications of endoscopic retrograde
      cholangiopancreatography and endoscopic ultrasound in an ambulatory endoscopy
      center.
AB  - BACKGROUND AND AIMS: Our aim was to assess the safety of endoscopic retrograde
      cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) in an ambulatory
      endoscopy center (AEC). METHODS: Complications occurring in consecutive patients
      undergoing ERCP or EUS from March 2003 to February 2004 at our AEC were recorded
      prospectively. Comprehensive complications were defined as consensus criteria
      plus other adverse events: use of reversal agents, unplanned hospital admission,
      hospitalization beyond planned 23-hour observation, unplanned emergency
      department or primary care provider visit, and 30-day mortality. RESULTS: A total
      of 497 patients (median age, 57 y; 82% American Society of Anesthesiologists
      class II or III) underwent 685 procedures. Monitored or general anesthesia was
      used in 25% of EUS and 50% of ERCP procedures. ERCP interventions were as
      follows: biliary or pancreatic stenting (N = 168), stone extraction (N = 70),
      sphincterotomy (N = 62), sphincter of Oddi manometry (N = 53), other (N = 66).
      EUS indications were as follows: known or suspected pancreatic mass (N = 103),
      upper-gastrointestinal mass/submucosal lesion (N = 71), luminal malignancy
      staging (N = 40), other (N = 96); 52% had EUS fine-needle aspiration. There was
      follow-up evaluation in 94% of the patients. There were 43 comprehensive ERCP
      complications (12.9%), 18 (5.4%) of these fit consensus criteria: pancreatitis (N
      = 14), cholangitis (N = 2), and perforation (N = 2). There were 9 comprehensive
      EUS complications (2.9%), 2 (.7%) of these fit consensus criteria: pancreatitis
      (N = 1) and bleeding (N = 1). Other adverse events for ERCP and EUS were as
      follows: prolongation of 23-hour observation (N = 14), emergency room visits (N =
      3), primary care physician visits (N = 6), use of reversal agents (N = 3),
      unplanned admissions (N = 2), infection (N = 3), and death (N = 1). CONCLUSIONS:
      ERCP and EUS can be performed in an AEC, provided mechanisms for admission and
      anesthesia support are in place. The assessment of comprehensive complications is
      more reflective of adverse events related to ERCP and EUS than consensus criteria
      alone.

PMID- 16797252
TI  - Immobilization stress increases endogenous monoamine oxidase (MAO) inhibitor in
      rat liver.
AB  - Although the physiological role of endogenous monoamine oxidase (MAO) inhibitor
      still remains unclear, the present study examined whether or not immobilization
      stress (IMMO) induce MAO inhibitor. An endogenous inhibitor of MAO was separated
      by gel filtration from 105,000 g supernate in rat liver cytosol following IMMO.
      The molecular weight of this inhibitor was estimated to be 500-600 by gel
      filtration. This inhibitor was proved to be heat-stable resistant to protease
      treatment. IMMO for 2 h significantly decreased MAO. These results suggest that
      this inhibitor is induced by IMMO. MAO activity in rat liver might be regulated
      by the level of this inhibitor.

PMID- 16797253
TI  - Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of
      genomic stability.
AB  - DNA damage response mechanisms encompass pathways of DNA repair, cell cycle
      checkpoint arrest and apoptosis. Together, these mechanisms function to maintain
      genomic stability in the face of exogenous and endogenous DNA damage. ATM is
      activated in response to double strand breaks and initiates cell cycle checkpoint
      arrest. Recent studies in human fibroblasts have shown that ATM also regulates a
      mechanism of end-processing that is required for a component of double strand
      break repair. Human fibroblasts rarely undergo apoptosis after ionising radiation
      and, therefore, apoptosis is not considered in our review. The dual function of
      ATM raises the question as to how the two processes, DNA repair and checkpoint
      arrest, interplay to maintain genomic stability. In this review, we consider the
      impact of ATM's repair and checkpoint functions to the maintenance of genomic
      stability following irradiation in G2. We discuss evidence that ATM's repair
      function plays little role in the maintenance of genomic stability following
      exposure to ionising radiation. ATM's checkpoint function has a bigger impact on
      genomic stability but strikingly the two damage response pathways co-operate in a
      more than additive manner. In contrast, ATM's repair function is important for
      survival post irradiation.

PMID- 16797254
TI  - Chromosomal translocations involving the MLL gene: molecular mechanisms.
AB  - A wide array of recurrent, non-random chromosomal translocations are associated
      with hematologic malignancies; experimental models have clearly demonstrated that
      many of these translocations are causal events during malignant transformation.
      Translocations involving the MLL gene are among the most common of these non
      random translocations. Leukemias with MLL translocations have been the topic of
      intense interest because of the unusual, biphenotypic immunophenotype of these
      leukemias, because of the unique clinical presentation of some MLL translocations
      (infant leukemia and therapy-related leukemia), and because of the large number
      of different chromosomal loci that partner with MLL in these translocations. This
      review is focused on the potential mechanisms that lead to MLL translocations,
      and will discuss aberrant VDJ recombination, Alu-mediated recombination, non
      homologous end joining, as well as the effect of DNA topoisomerase II poisons and
      chromatin structure.

PMID- 16797256
TI  - 'Peeling paint' dermatitis as a presenting sign of cystic fibrosis.
AB  - Presentation of cystic fibrosis with a rash is rare, with only 19 previously
      reported cases. This unusual presentation is associated with false negative sweat
      tests, delays in diagnosis and considerable mortality. Multiple nutritional
      deficiencies, the aberrant production of prostaglandins and free-radical mediated
      damage have been implicated in the pathogenesis of this kwashiorkor-like
      dermatitis. In spite of the rarity of this presentation, recognition of the rash
      is important, not only to expedite the diagnosis, but also to gain insight into
      the disease. We present a further case to highlight this unusual presentation and
      discuss potential pathophysiological mechanisms.

PMID- 16797255
TI  - Identification of MMS19 domains with distinct functions in NER and transcription.
AB  - Nucleotide excision repair (NER) and RNA polymerase II (Pol II) transcription are
      essential cellular processes which are intimately intertwined. They share an
      indispensable multiprotein complex, TFIIH, and impairments in either process can
      impact the efficiency of the other. Like TFIIH, MMS19 is required for NER and Pol
      II transcription, but its precise role in each process is unknown. We showed
      previously that the human MMS19 gene originates multiple splice variants, some of
      which may encode distinct MMS19 protein isoforms. Here we characterize a novel
      MMS19 transcript and demonstrate for the first time that MMS19 splice variants
      are conserved across species and are functionally distinct. Expression of human
      MMS19 splice variants in mms19-deleted yeast cells produced unique patterns of
      thermosensitivity and ultraviolet radiation-sensitivity that point to three MMS19
      structural domains with distinct in vivo functions. MMS19 polypeptides lacking
      domain A are able to fulfill the role of full-length MMS19 in NER but not in
      transcription. MMS19 polypeptides lacking part of domain B are efficient in
      transcription but not in NER. MMS19 polypeptides lacking domain C (HEAT repeats)
      are unable to fulfill either function. Our data suggest that the MMS19 HEAT
      repeat domain is essential for MMS19 function in NER and transcription, while
      domains A and B, within MMS19 N-terminus, modulate the balance between DNA repair
      and transcription. Our results highlight the functional significance of MMS19
      transcripts and the possible contribution of MMS19 isoforms to regulate the
      switch between NER and transcription. Furthermore, our work associates for the
      first time specific protein domains with MMS19's role in NER and transcription.

PMID- 16797257
TI  - Pregnancy in cystic fibrosis lung transplant recipients: case series and review.
AB  - A single centre experience of four pregnancies in four cystic fibrosis (CF) lung
      transplant recipients is reported. Six more cases were identified from the
      literature review and combined data analysis on 10 pregnancies in 10 CF lung
      transplant recipients was performed to determine maternal, foetal and graft
      outcome. There were nine live births and one therapeutic abortion. Three required
      caesarean sections. Five babies were premature but all nine children were well at
      follow-up. Five recipients who had a long, stable interval (i.e. at least three
      years) between transplant and pregnancy had a favourable outcome. Three
      recipients developed rejection during the pregnancy and one already had
      obliterative bronchiolitis before pregnancy. All showed progressive decline in
      lung function and subsequently died of chronic rejection within 38 months of
      delivery. Pregnancy in CF lung transplant recipients is feasible but should still
      be regarded as a risky undertaking.

PMID- 16797258
TI  - Chiral separation and quantification of R/S-amphetamine, R/S-methamphetamine, R/S
      MDA, R/S-MDMA, and R/S-MDEA in whole blood by GC-EI-MS.
AB  - The enantioselective composition of the amphetamines is of interest, as the
      enantiomers show differences in their pharmacological effects and several methods
      for chiral separation of amphetamines have been described. Only a few methods
      have used whole blood as matrix and none of these separates both classic
      amphetamines (amphetamine and methamphetamine) and designer amphetamines (MDA,
      MDMA and MDEA). The aim of this study was, therefore, to develop a method for
      enantioselective analysis of AM, MA, MDA, MDMA, and MDEA in whole blood. The
      amphetamines were extracted from 0.5 g of whole blood by liquid-liquid
      extraction. After derivatization with R-MTPCl, the resulting diastereomers were
      separated by GC on a HP-5MS column and detected by SIM-MS. R-MTPCl was used as
      derivatization reagent because of the stability of this reagent and good
      separation of these analytes. Through the method, development time and
      temperature of the derivatization were optimized, and by admixture of 0.02%
      triethylamine it became possible to detect the amphetamines in adequately low
      concentrations as more analytes were derivatized. The method was validated and it
      was linear from 0.004 to 3 microg/g per enantiomer. The accuracy was within 91
      115%, while the repeatability and reproducibility were < or =15% R.S.D. A method
      suitable for enantioselective separation and analysis of the amphetamines has
      been achieved, and the method was applied to analysis of whole blood samples
      originating from traffic and criminal cases and post mortem cases.

PMID- 16797259
TI  - The proteome of dissimilatory metal-reducing microorganism Geobacter
      sulfurreducens under various growth conditions.
AB  - The proteome of Geobacter sulfurreducens, a model for the Geobacter species that
      predominate in many Fe(III)-reducing subsurface environments, was characterized
      with ultra high-pressure liquid chromatography and mass spectrometry using
      accurate mass and time (AMT) tags as well as with more traditional two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE). Cells were grown under
      six different growth conditions in order to enhance the potential that a wide
      range of genes would be expressed. The AMT tag approach was able to identify a
      much greater number of proteins than could be detected with the 2-D PAGE
      approach. With the AMT approach over 3,000 gene products were identified,
      representing about 90% of the total predicted gene products in the genome. A high
      proportion of predicted proteins in most protein role categories were detected;
      the highest number of proteins was identified in the hypothetical protein role
      category. Furthermore, 91 c-type cytochromes of 111 predicted genes in the G.
      sulfurreducens genome were identified. Differences in the abundance of
      cytochromes and other proteins under different growth conditions provided
      information for future functional analysis of these proteins. These results
      demonstrate that a high percentage of the predicted proteins in the G.
      sulfurreducens genome are produced and that the AMT tag approach provides a rapid
      method for comparing differential expression of proteins under different growth
      conditions in this organism.

PMID- 16797260
TI  - Compatible solutes as protectants for zymogens against proteolysis.
AB  - Compatible solutes are small organic osmoprotectants that have the capability to
      stabilize proteins. In coupled assays, the effect of the solutes ectoine,
      hydroxyectoine and betaine on the activation of the zymogens trypsinogen and
      chymotrypsinogen, catalyzed by enteropeptidase and trypsin, respectively, was
      studied. To different extents, all solutes protected the zymogens against
      activation. Ectoine (800 mM) was the most potent solute in reducing the formation
      of trypsin to 4% of the control value and of chymotrypsin to 23%. In separate
      experiments, the ability of the solutes to preserve proteolytic activity during
      incubation was investigated. After 4 h, trypsin and chymotrypsin completely lost
      their activity, but in the presence of ectoine, approximately 50% residual
      activity was maintained. It is proposed that a conformational shift of the
      protein towards folded, native-like states induced by preferential exclusion of
      the solute is responsible for the stabilizing and chaperone-like effects.

PMID- 16797261
TI  - Effect of bicarbonate on the water-oxidizing complex of photosystem II in the
      super-reduced S-states.
AB  - It is shown that the hydrazine-induced transition of the water-oxidizing complex
      (WOC) to super-reduced S-states depends on the presence of bicarbonate in the
      medium so that after a 20 min treatment of isolated spinach thylakoids with 3 mM
      NH(2)NH(2) at 20 degrees C in the CO(2)/HCO(3)(-)-depleted buffer the S-state
      populations are: 42% of S(-3), 42% of S(-2), 16% of S(-1) and even formal S(-4)
      state is reached, while in the presence of 2 mM NaHCO(3), the same treatment
      produces 30% of S(-3), 38% of S(-2), and 32% of S(-1) and there is no indication
      of the S(-4) state. Bicarbonate requirement for the oxygen-evolving activity,
      very low in untreated thylakoids, considerably increases upon the transition of
      the WOC to the super-reduced S-states, and the requirement becomes low again when
      the WOC returns back to the normal S-states using pre-illumination. The results
      are discussed as a possible indication of ligation of bicarbonate to manganese
      ions within the WOC.

PMID- 16797263
TI  - Hippocampal neurogenesis: regulation by stress and antidepressants.
AB  - Accumulating evidence implicates hippocampal neurogenesis in the pathophysiology
      of depression. Psychosocial stress reduces neurogenesis in rodents, whereas
      chronic treatment with antidepressants increases neurogenesis and blocks the
      effects of stress. The effects of stress and antidepressant treatment on
      hippocampal neurogenesis parallel behavioral changes in animal models. Moreover,
      ablating hippocampal neurogenesis renders antidepressants inactive in behavioral
      paradigms used to model antidepressant response and anxiety-like behavior in
      mice. In humans, monoamine-modulating antidepressants demonstrate clinical
      efficacy in treating depression and anxiety, which are often precipitated by
      psychosocial stress. This review examines the mounting evidence that stress and
      antidepressant treatment regulate neurogenesis in animals. Special attention is
      paid to the cellular and molecular mechanisms by which this regulation takes
      place. An analysis of current animal models used to study response to stress and
      antidepressants indicates the importance of modeling chronic treatment, which
      reflects both changes in neurogenesis and clinical response. Exploring responses
      of hippocampal neurogenesis to experimental challenges in appropriate animal
      models should delineate the role of adult-born neurons in hippocampal physiology.
      Focusing on neurogenic response to experimental paradigms of stress and
      antidepressant treatment is particularly interesting for understanding the
      pathophysiology of major depressive disorder.

PMID- 16797264
TI  - A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition,
      and mental conditions.
AB  - Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for
      schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be
      elucidated. Accumulating genetic evidence supports that DISC1 is associated with
      some aspects of cognitive functions relevant to SZ and BP. Here, we provide a
      summary of the current updates in biological studies of DISC1. Disrupted-In
      Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms
      with potential posttranslational modifications. Disrupted-In-Schizophrenia-1
      protein occurs in multiple subcellular compartments, which include the
      centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal
      fractions, the mitochondria, and the nucleus. Recent studies have clarified that
      DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine
      monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological
      studies consistently suggest that an overall loss of DISC1 function (either
      haploinsufficiency or dominant-negative, or both) may be associated with SZ and
      BP. On the basis of these findings, production of DISC1 genetically engineered
      mice is proposed as a promising animal model for SZ and BP. Several groups are
      currently generating DISC1 mice and starting to characterize them. In this
      review, the advantages and disadvantages of each animal model are discussed.

PMID- 16797266
TI  - Comparison between transcranial color Doppler ultrasonography and angiography in
      the confirmation of brain death.
AB  - OBJECTIVE: Cerebral blood flow tests have increasingly been advocated for the
      confirmation of brain death (BD). Angiography has been considered the gold
      standard in the diagnosis of BD but is invasive. We validated transcranial color
      Doppler ultrasonography (TCD) to confirm BD by comparing it to angiography.
      PATIENTS AND METHODS: Forty patients experienced the clinical diagnosis of brain
      death due to head injury in 19 cases (47.5%), cerebral hemorrhage in 11 (27.5%),
      subarachnoid hemorrhage in 7 (17.5%), and cerebral infarction in 3 (7.5%). Blood
      pressure, heart rate, SPO2, and PCO2 were monitored throughout the study.
      Patients were excluded if episodes of hypoxia, arrhythmia, and hypotension
      occurred during examinations, or if the TCD was not technically feasible.
      RESULTS: Both angiography and TCD confirmed BD in all patients. The agreement
      between the above methods to confirm BD was 100%. Angiography showed the absence
      of filling of intracranial arteries, while TCD revealed: (1) brief systolic
      forward flow or systolic spikes and diastolic reversed flow (50%); (2) brief
      systolic forward flow or systolic spikes and no diastolic flow (25%); (3) no
      demonstrable flow in a patient in whom flow had been clearly documented on a
      previous TCD examination (12.5%). Five patients required repeated TCD
      examinations, because of initial detection of a diastolic to-and-fro flow
      pattern. BD was confirmed by TCD in the above patients after 30 hours of clinical
      BD. CONCLUSION: TCD was a sensitive tool to diagnose BD, affording a reliable
      alternative examination to standard angiography.

PMID- 16797267
TI  - Public knowledge and attitudes on organ donation do not differ in Germany and
      Spain.
AB  - BACKGROUND: The background of this study was the inadequate supply of donor
      organs in Germany. In Spain, by contrast, a strong increase of organ donors over
      the past years has created a satisfactory supply situation. Because both
      countries have similar legal situations, the causes for the drastic differences
      in organ donation rates remain unclear. The main issue of our study was to
      investigate the intellectual attitudes toward various aspects of postmortem
      donations in the populations of both countries as a causative factor for the
      observed differences. METHODS: We studied 726 persons by questionnaire. Probands,
      matched for age and gender, were recruited among medical students, in a public
      library and in a general medical practice in both Germany and Spain. RESULTS: We
      found no differences in the attitudes toward postmortem organ donation between
      the two countries. Differences among the social groups within the countries were
      apparent in the expected direction. CONCLUSION: A higher level of knowledge or a
      difference in attitudes toward organ donation is probably not the reason for the
      higher donation rate in Spain. The cause appears to be rather at the
      organizational level.

PMID- 16797268
TI  - Drug use and kidney donation: what are high-risk behaviors today?
AB  - BACKGROUND: "Social risk behaviors" are usually considered as contraindications
      for organ donation. The organ shortage, however, necessitates expansion of the
      donor pool. Reconsideration of the policy toward substance abusers may be
      important. Opinions of the overall population may be of use to define this
      cultural-sensitive issue. METHODS: A semistructured questionnaire on organ
      donation, including opinions on drug use (cannabis and cocaine), was administered
      to various groups of the general public and caregivers: high school students
      (liceo classico: 59 students, median age 18 years; istituto tecnico: 108, age
      17); first- and fourth-year medical school (77, age 19; 46, age 22); continuing
      medical education (44, age 32); third-year nursing school (31, age 23); "senior
      citizen university" (51, age 63). RESULTS: Cannabis use was mainly accepted for
      kidney donation (48.6% yes, 26.6% no, 29.8% uncertain/blank), but cocaine use was
      not (22.1% yes, 44.2% no, 33.7% uncertain/blank). In the univariate analysis,
      opinions differed according to age, sex, and belonging to the health care teams
      upon multivariate analysis being a member of the health care team was the
      strongest predictor of responses (P<.01). CONCLUSION: It is difficult to define
      social risk behaviors. Since opinions are important for organ donation, further
      studies and discussion are needed to periodically analyze our policies.

PMID- 16797265
TI  - Schizophrenia-relevant behavioral testing in rodent models: a uniquely human
      disorder?
AB  - Animal models are extremely useful tools in defining pathogenesis and treatment
      of human disease. Creating adequate animal models of complex neuropsychiatric
      disorders such as schizophrenia represents a particularly difficult challenge. In
      the case of schizophrenia, little is certain regarding the etiology or
      pathophysiology of the human disease. In addition, many symptoms of the disorder
      are difficult to measure directly in rodents. These challenges have not daunted
      neuroscientists who are capitalizing on even subtle overlaps between this
      uniquely human disorder and rodent behavior. In this perspective, we detail the
      features of ideal animal models of schizophrenia, the potential utility of such
      models, and the rodent behaviors used to model certain aspects of schizophrenia.
      The development of such models will provide critical tools to understand the
      pathogenesis of schizophrenia and novel insights into therapeutic approaches to
      this complex disorder.

PMID- 16797269
TI  - Is male homosexuality still a cultural taboo for kidney donation?
AB  - BACKGROUND: Among the so-called social risk behaviors, male homosexuality is
      probably one of the most interesting and difficult taboos. Because of changing
      attitudes of the general population toward irregular sexual behaviors, often
      considered as markers of unhealthy life styles, there is a need to reconsider at
      least the most important one-homosexuality. METHODS: A semistructured
      questionnaire included opinions on homosexuality with respect to kidney donation:
      Would you consider a male homosexual as a kidney donor? If you were on dialysis,
      would you accept a kidney from a homosexual donor? This instrument was
      administered to various groups of the general public and caregivers: high school
      students (Liceo Classico: 59 students, median age 18 years; Istituto Tecnico:
      n=108, median age 17); first and fourth year of medical school (n=77, age 19; 46,
      age 22); continuing medical education (n=44, age 32); third year of nursing
      school (n=31, age 23); "senior citizen university" (n=51, age 63). RESULTS: Male
      homosexuality was well accepted for kidney donation (71.6% yes, 9.6% no, 18.8%
      uncertain/blank). However, the opinions were different among the groups with male
      students of a technical institute showing discrimination against male
      homosexuals. In the univariate analysis, opinions differed according to age,
      gender, and belonging to the health care team. In the multivariate analysis, the
      latter was the strongest predictor (P<.01). The specific threats for the health
      are not well known, even among the caregiver population. CONCLUSION: It is
      difficult to define the role of homosexuality among the so-called social risk
      behaviors. Negative attitudes existed in some subsets of the population.

PMID- 16797270
TI  - Effects of polyethylene glycol and hydroxyethyl starch in University of Wisconsin
      preservation solution on human red blood cell aggregation and viscosity.
AB  - University of Wisconsin (UW) preservation solution is considered an effective
      flush and cold storage liquid. However, recent studies have provided evidence of
      the hyperaggregating effect on human red blood cells (RBC) of hydroxyethyl starch
      (HES), one of the components of the UW solution. In contrast, preservation
      solutions containing polyethylene glycol (PEG) have been found to be effective
      for organ preservation. The aim of this study was to compare the effects of HES
      (50 g/L); PEG 20 kDa (50 and 30 g/L), and PEG35 kDa (1.05 g/L) added to UW on the
      rheologic parameters of human RBC at 4 degrees C. Sedimentation rate was measured
      by the Westergren procedure and blood viscosity evaluated at high shear rates
      using a cone/plate viscometer. Alterations in RBC morphology and aggregation were
      evaluated by light microscopy. RBC sedimentation and viscosity were not affected
      by the inversion of Na+ and K+ concentrations in UW, but were increased by HES.
      PEGs appeared to reduce RBC deformability with concomitant inhibition of RBC
      aggregation. These results were consistent with reduced viscosity for PEG
      containing solutions. In conclusion, the use of PEG did not change the
      physiologic function of human RBCs and thus may be an alternative to HES in UW
      liquids.

PMID- 16797271
TI  - Evaluation of hepatic function after orthotopic liver transplantation: a
      comparative study using Belzer and Collins solutions.
AB  - Belzer and Collins are solutions used in liver transplantation. The purpose of
      this study was to compare liver function after utilization of two different
      schemes of graft preservation using both solutions. Between December 2004 and
      September 2005, 43 liver transplantations were performed. Twenty-three of these
      used 2 L of Collins solution and 2 L of Belzer solution as the preservation
      solution. The others used three L of Collins and 1 L of Belzer solution as the
      preservation solution. The cold ischemia time of both groups was similar. We
      analyzed liver function using the serum ALT, AST, bilirubin and international
      normalized ratio. On the first day after the transplantation, the level of
      international normalized ratio of the group of patients that used 1 L of Belzer
      was significantly higher than the other group (P<.05). The levels of ALT, AST,
      and bilirubin were not different on day 7 after transplantation. We concluded
      that using only 1 L of Belzer solution is as efficient with the advantage that it
      is less expensive.

PMID- 16797272
TI  - Machine perfusion preservation of the pig liver using a new preservation
      solution, polysol.
AB  - INTRODUCTION: The current gold standard for donor liver preservation is cold
      storage in a preservation solution (4 degrees C), such as Celsior or the
      University of Wisconsin solution (UW). Recent studies have suggested the benefits
      of machine perfusion (MP) over cold storage. To improve the results of MP, an
      enriched preservation solution (named Polysol) was developed, which in a rat
      liver preservation model proved to be superior to the UW-gluconate solution. The
      aim of this study was to assess Polysol in a pig liver preservation model.
      MATERIALS AND METHODS: Female pigs (35 to 40 kg) were used as liver donors. After
      heparinization, the liver was washed out using Ringer's lactate, followed by the
      preservation solution (4 degrees C). The liver was preserved for 24 hours by
      either cold storage using Celsior (n=5) or MP using Polysol (n=5). For analysis
      of liver damage and function, livers were reperfused for 60 minutes using
      oxygenated Krebs-Henseleit buffer. RESULTS: CS-Celsior caused significantly more
      damage compared with MP-Polysol (t=60, AST: 622+/-215 versus 222+/-55; ALT: 17+/
      6 versus 5+/-1). Intravascular resistance during reperfusion was significantly
      higher after CS-Celsior compared with MP-Polysol (t=0, 0.20+/-0.01 and 0.11+/
      0.02 mm Hg/mL/min, respectively). No differences were seen regarding ammonia
      clearance and urea production. In both groups, no bile was produced during
      reperfusion. CONCLUSIONS: In an ex vivo pig liver preservation model
      significantly less damage was observed after machine perfusion preservation using
      Polysol, in comparison to cold storage using Celsior.

PMID- 16797273
TI  - Molecular markers in stored kidneys using perfluorocarbon-based preservation
      solution: preliminary results.
AB  - BACKGROUND: Delayed graft function (DGF) is a problem in kidney transplantation
      and cold ischemia has been identified as a risk factor. Perfluorocarbons (PFC)
      have an enhanced ability to dissolve and release oxygen. We evaluated
      histologically and a number of molecular changes induced by ischemia in stored
      kidneys with University of Wisconsin (UW) and PFC-based preservation solutions
      (PFC-UW). MATERIALS AND METHODS: ACI rats were used as kidney donors. UW (control
      group) or PFC-UW (study group) preservation solutions were used for kidney
      perfusion. All kidneys were stored at 4 degrees C for 12, 24, and 36 hours. After
      this time, intragraft histologic evaluation as well as mRNA HO-1 and iNOS levels
      were also analyzed. RESULTS: In the kidneys stored at 24 hours, mRNA HO-1 levels
      were elevated in the study group when compared with the control and mRNA iNOS was
      decreased. CONCLUSION: We observed overexpression of HO-1 and underexpression of
      iNOS in the kidney tissue stored with PFC-UW solution at 24 hours. These
      preliminary data suggest that increasing oxygen delivery by PFC added to the
      perfusion solution triggers cytoprotective mechanism in kidney transplantation.

PMID- 16797274
TI  - Protective role of 3-nitro-N-methyl-salicylamide on isolated rat heart during 4
      hours of cold storage and reperfusion.
AB  - OBJECTIVE: Cardiac ischemia/reperfusion (I/R) injury, a necessary consequence of
      transplantation, is probably related to the formation of reactive oxygen species
      (ROS). The ROS burst within the first moments of reperfusion is associated with
      injury, continuously generate O2- at about 3% to 5% of total O2 consumption owing
      to electron leak by mitochondrial oxidoreductases, especially complexes I and
      III. 3-nitro-N-methyl-salicylamide (NNMS) displays inhibitory effects on
      succinate-cytochrome C reductase, but also reduces effects on creation of O2-
      radical and H2O2 by isolated rat mitochondria. Presumably NNMS inhibits electron
      leakage from the mitochondrial respiratory chain. We investigated effect of NNMS
      on heart protection after hypothermic ischemia. METHODS: A Langendorff-prepared
      rat heart model was employed after the heart had been preserved for 4 hours under
      hypothermic conditions of ischemia with subsequent reperfusion/rewarming for 60
      minutes. RESULTS: The group of hearts treated with NNMS showed increased recovery
      of heart function compared with a group of mEC. The lactate dehydrogenase (LDH)
      activity in coronary flow (CF) by hearts treated with NNMS was lower than that
      with mECs, as was the content of malonedialdehyde (MDA) and conjugated diene
      (CD). CONCLUSIONS: NNMS improved heart physiology after reperfusion following 4
      hours of hypothermic ischemia.

PMID- 16797275
TI  - Effect of combining phosphodiesterase III inhibitors with St Thomas Hospital's
      solution used as transplantation preservative solution in isolated rat hearts.
AB  - Improved preservation of the harvested heart with attenuation of the reperfusion
      injury is important for successful outcomes of cardiac transplantations. The most
      commonly used cardioplegic solution, to prevent ischemic changes has been St
      Thomas' Hospital cardioplegic solution (STHCS). However, it is neither ideal nor
      sufficient to prevent myocardial ischemia and reperfusion injury.
      Phosphodiesterase inhibitors can attenuate the damage due to the injuries of
      ischemia and reperfusion. In this study we sought to enrich STHCS with a
      phosphodiesterase inhibitor to improve preservation of cardiac functions. The
      harvested hearts of 24 rats were divided into four groups. All hearts were
      mounted on a Langendorff perfusion system. After a stabilization period, cardiac
      arrest was maintained by STHCS. The hearts were stored in STHCS alone or with
      milrinone, amrinone, or enoximone for 6 hours. The reperfusion was maintained
      using a modified Tyrode's solution. All hearts were compared for their
      preischemic and postischemic left ventricular developed pressure, +dp/dtmax, 
      dp/dtmax, duration of systole, ejection time, and time to reach peak systolic
      pressure. Coronary effluent was collected for lactate dehydrogenase (LDH)
      measurements. The initial values for all metrics were comparable between the
      groups. During the postreperfusion period, all hearts showed lower peak systolic
      pressures than the initial values. Although the amrinone group seemed to have
      higher values, the 25-minute result was at the border of significance and the 30
      minute value, significantly higher. All hearts showed far lower results of
      maximum changes in contractility during the time period (+dp/dtmax) versus the
      initial values; comparisons between groups were not significant. For the
      parameter of maximum changes in relaxation during the time period (-dp/dtmax),
      while other hearts showed lower results, the amrinone group displayed values
      comparable to the initial ones after 20 minutes. Comparisons between groups were
      insignificant. While other hearts had comparable values for time of systole, the
      hearts applied with milrinone reached these values after 15 minutes. Group
      comparison for time of ejection revealed that the results at 5-minute
      postreperfusion were higher in the enoximone and the amrinone groups than the
      milrinone group. Postreperfusion 5-minute results were higher in the enoximone
      and the amrinone groups than the milrinone group for time to reach peak systolic
      pressure. LDH levels were lowest in the amrinone group. In conclusion, our study
      revealed that adding phosphodiesterase inhibitors to STHCS improved peak systolic
      pressure and maximum changes in relaxation during the time period (-dp/dtmax, mm
      Hg/s). It also decreased the LDH leakage, which corresponded to the degree of
      ischemic tissue damage. Amrinone seemed to result in more favorable results,
      which may be attributed to its additional effects on inflammation, including
      those on cytokines and leukocyte aggregation.

PMID- 16797276
TI  - Complications of arteriovenous fistula in dialysis patients.
AB  - Repeated access to the circulation is essential to perform adequate maintenance
      hemodialysis (HD). Dysfunction of fistulae is the most common reason for a second
      intervention and recurrent hospitalization. The aim of this study was to evaluate
      the complications of HD fistulas seeking to evaluate the impact of age, site of
      arteriovenous fistula (AVF) (proximal or distal), side (left or right), and
      history of previous vascular access. We evaluated the clinical complications in
      273 patients from the beginning of the use of the current access using the
      history and physical examination obtained at every dialysis session. We performed
      further investigations including doppler ultrasound or spiral computed tomography
      to confirm the clinical diagnosis. Of our patients, 40% had diabetes mellitus as
      the cause of end-stage renal disease. Almost half (49%) the patients dialyzed
      through an AVF and 13% with a catheter. One hundred eighty-four cases (67.6%)
      experienced complications. Of 145 cases that had elbow AVFs, 103 cases (71%) had
      complications; of 128 cases with wrist AVFs, 80 cases (62.5%) had complications.
      There were 115 (62.5%) complicated cases among 185 patients with left AVFs, and
      69 (78%) among 88 patients with right AVFs. The rate of AVF complications
      increased with age. The 1-year survival rate was 94%. We did not observe any
      significant difference between AVF complications in patients with diabetes
      mellitus or hypertension as the underlying cause of renal failure. Mean
      cholesterol plasma level did not differ significantly between the patients with
      and without AVF complications. Mean hematocrit levels were not significantly
      different between the two groups. However, mean EPO weekly dose was significantly
      higher among the group of patients with AVF complications. We did find that rate
      of complications increased with age (P<.05). Our results showed that the
      frequency of complications was higher among patients with elbow and right-side
      AVFs, and also among patients with a history of a previous failed shunt but no
      significant relationship was observed between these variables (P>.05).

PMID- 16797277
TI  - Difficult vascular access in patients with end-stage renal failure.
AB  - BACKGROUND/AIM: End-stage renal failure patients requiring long-term hemodialysis
      need a durable vascular access. The arteriovenous fistula (AVF) with its long
      patency rate and low complication profile is usually the first choice for
      vascular access creation. However, when superficial veins are not suitable for
      AVF creation or all have been exhausted as a result of repeated AVF procedures,
      arteriovenous grafts (AVGs) using expanded polytetraflouroethylene (ePTFE) is an
      alternative. This study reviewed our experience in using PTFE AVGs for vascular
      access in patients requiring chronic hemodialysis. MATERIALS AND METHODS: In a
      prospective study, from September 2002 to October 2004, 21 PTFE AVGs were placed
      in 21 patients. We evaluated the complications and patency. RESULTS: There were
      12 female and nine male patients of mean age 58+/-8.7 years (range=45 to 76
      years). Nine patients (43%) had hypertensive nephrosclerosis, 6 (29%) diabetic, 2
      (10%) glomerulonephritis, 3 (14%) systemic lupus erythematosis requiring long
      term steroids, and 1 (4.7%) unknown cause. The patency rate at 24 months was
      85.7%. Complications included graft thrombosis (three; 14.3%), wound infection
      (three; 14.3%) and graft infection (one; 4.8%). CONCLUSION: ePTFE AVGs offer
      reasonable patency and serviceability rates as a vascular access modality, but in
      view of their complication profile, the native vein arteriovenous fistula should
      continue to be the first choice for vascular access for patients requiring
      chronic hemodialysis.

PMID- 16797278
TI  - Analysis of L-myc gene polymorphism in patients with renal failure outcome to
      renal transplant.
AB  - BACKGROUND: Abnormalities of cell numbers and apoptosis have been observed in
      renal failure. As uncontrolled expression of c-myc is known to induce apoptosis,
      we thought that polymorphism in the other myc gene, L-myc gene, which is
      structually similar to c-myc and reported to be expressed in the kidney, may have
      a role in the induction of apoptosis and thus have role in chronic renal failure.
      The aim of this study was to investigate the relationship between the
      distribution of L-myc genotypes and renal failure. METHODS: In the present study
      we examined 101 chronic renal failure patients who had either live or cadaveric
      renal transplants and 105 healthy individuals, for L-myc gene polymorphism by
      polymerase chain reactions and restriction fragment length polymorphism
      techniques. RESULTS: Among our patient group, the distribution of the LL, LS, and
      SS genotypes was 24% (n=25), 71% (n=71), and 5% (n=5), respectively, versus 41%
      (n=43), 47% (n=49), and 12% (n=13) in our control group. The distribution of
      genotypes was significantly different between our patients and the control group
      (chi2=12.281; P=.002). The frequency of the S allele was significantly higher in
      the patient group (chi2=6.122; P=.013). CONCLUSION: Our study showed that having
      an S allele in the L-myc gene may increase the risk of renal failure.

PMID- 16797279
TI  - Correlation between the biopsies in marginal donor kidneys for transplantation:
      is it necessary to biopsy both kidneys?
AB  - OBJECTIVES: The objective of this study was to analyze the correlation between
      histological findings in both transplanted kidneys from marginal donors. METHODS:
      We retrospectively reviewed the histological information on 92 kidneys obtained
      between January 2001 and January 2004, corresponding to 46 marginal donors.
      Criteria for biopsy were age greater than 55 years, hypertension, diabetes, and
      proteinuria. Scores were established by the pathologist including
      glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis.
      The score for each lesion was classified as 0 if absent; 1 if <20%; 2 if >20% and
      <50%; and 3 if >50%. Finally, we defined an index of renal severity damage (RSD)
      in order to classify the kidneys for single transplantation (0), double
      transplantation (1), and unsuitable for transplantation (2). RESULTS: Of the
      kidneys studied, 82.6% of both kidneys showed similar degrees of
      glomerulosclerosis (<20% in 71.7% and >20% in 10.9%), while 17.4% showed
      discrepancies (> vs <20%; P=.008). On the other hand, RSD correlated in 82.6% of
      both kidneys (in 69.6% RSD=0; in 8.7% RSD=1; and in 4.3% RSD=2), while 17.4%
      showed discrepancies (P=.001). In one case (2.2%), a great discrepancy was
      observed; one kidney was valid for single transplantation, and the other one not
      valid for any transplantation, single or double. CONCLUSIONS: This study
      demonstrated a correlation between the biopsy findings in both kidneys in 82.6%
      of marginal organ donors. However, in 17.4% of cases we observed discrepancies.
      The degree of glomerulosclerosis seemed to be a powerful parameter to define
      renal severity damage. According to these results we would recommend biopsy of
      both kidneys.

PMID- 16797280
TI  - Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation
      in China.
AB  - OBJECTIVE: In this study, the effects of Triptergium Wilfordii Hook F.(T II) were
      assessed on human kidney allograft rejection and long-term survival. METHODS:
      This study compared treatment with T II(T II group, n=121) to that without T
      II(control group, n=102) among adult first cadaveric renal transplant recipients.
      The T II cohort of 121 recipients were divided into a regular dosage group (n=82)
      and a double dosage group (n=39). No antibody induction was administered to any
      patient. RESULTS: Biopsy-proven early acute allograft rejection occurred in 4.1%
      of patients in the T II group versus 24.5% of patients in the control group. No
      rejection or repeated rejections occurred in the double dosage group at 3 months
      after transplantation. Acute rejection episodes were milder in the T II than the
      control group. The incidence of CD25+ cells>10/ mm3 in the allografts at 3 months
      after transplantation was lower in the T II group than the control group, 15% and
      50%, respectively. All patients tolerated T II well over the 5 years of this
      study. The 5-year graft survival censored for death with function was 96.7% in
      the T II group and 80.4% in the control group. CONCLUSION: T II was effective to
      prevent renal allograft rejection and increase long-term renal allograft survival
      among adult cadaveric renal transplant recipients.

PMID- 16797281
TI  - Successful living related kidney transplantation across an anti-donor HLA
      antibody.
AB  - In preconditioning highly sensitized kidney transplant candidates, renal
      allograft outcomes have been better when the serum titer for class I anti-HLA
      donor-specific antibody (DSA) is low in the recipient at the time of
      transplantation. However, the ideal level to which the titer should be lowered is
      still controversial. We report a primary living related kidney transplant in a 34
      year-old highly sensitized woman (pretransplant panel-reactive antibody=70%) with
      end-stage renal disease secondary to chronic glomerulonephritis. We sought to
      desensitize by lowering the DSA titer specifically to 1:4 pretransplant. A
      standard complement-dependent cytotoxicity cross-match with her donor (sister)
      was repeatedly negative, although she was positive for class I antibody against
      her mismatched HLA antigen (A*2402) at a titer up to 1:16 by the single-antigen
      flowbead assay. The target DSA titer of 1:4 before transplant was achieved by 12
      sessions of plasmapheresis (PP) over 7 weeks, plus two intravenous immune
      globulin infusions (IVIG) (500 mg/kg/infusion). The patient outcome was
      excellent. Neither IVIG nor PP was needed posttransplant. The serum creatinine
      ranged between 0.5 mg/dL and 1.2 mg/dL, and no rejection episode was documented
      at 28 weeks posttransplant. Therefore, we encourage the use of IVIG and PP to
      lower the DSA titer to at least 1:4 before kidney transplantation in highly
      sensitized patients. Large prospective trials are needed to establish a consensus
      for pretransplant risk assignment and to evaluate the need for desensitization.

PMID- 16797282
TI  - Quality of life and psychosocial factors in renal transplant recipients.
AB  - An ideal method for quality of life (QOL) assessment in renal transplant
      recipients (RTR) has not yet been determined. Present assessments of QOL in RTR
      are lengthy, cumbersome to administer, and difficult to interpret. We used a
      previously validated single question QOL scale score (QLS) that directly asks
      about the patients' overall assessment of their QOL; "Considering all parts of my
      life-physical, emotional, social, spiritual, and financial--over the past 2 days
      the quality of my life has been ... ". The QLS ranges from 0 ("very bad") to 10
      ("excellent"). Patients were contacted prior to their routine office visit when
      they were free of acute medical problems. Fifty RTR participated. Psychosocial
      and medical variables included the Beck Depression Inventory, Illness Effects
      Questionnaire, Multidimensional Scale of Perceived Social Support, time since
      transplant, age, creatinine, hemoglobin, and albumin levels. Of the patients, 64%
      were African-American and 48% were women; 94% of patients had a score>5. Mean QLS
      was 7.5+/-2.3. Perception of a better QOL correlated with less perception of
      depression and illness effects and with perception of greater social support and
      satisfaction with life (all P<.05). Perception of QOL did not correlate with age,
      time since transplantation, creatinine, hemoglobin or albumin levels. We
      concluded that QLS is a quick tool to measure subjective QOL in RTR for
      correlation with psychosocial factors of interest in this group. These studies
      should be replicated in larger multiethnic populations.

PMID- 16797283
TI  - Correlation of C0 and C2 levels with lipid profiles in adolescent renal
      transplant recipients in the early and late posttransplant periods.
AB  - Hyperlipidemia is a frequent complication after renal transplantation.
      Cyclosporine therapy is an important cause of hyperlipidemia. It is still
      controversial whether C0 or C2 is the most effective way to monitor blood
      cyclosporine concentrations to guide dosages. We sought to evaluate the
      relationship of C0 or C2 to serum lipid levels in the early and late
      posttransplant periods among adolescent renal transplant recipients. The
      posttransplantation charts of 26 adolescent renal transplant recipients were
      evaluated retrospectively. Serum C0 and C2 levels and serum lipid (triglyceride
      and total cholesterol) levels were analyzed both in the early (first 6 months)
      and the late (thereafter) posttransplant periods. Hypertriglyceridemia and
      hypercholesterolemia were defined as levels above the 95th percentile adjusted
      for age and gender. To evaluate the influence of C0 and C2 levels on serum
      lipids, we excluded one patient with familial hyperlipidemia. In addition, serum
      lipid levels of the remaining 25 patients were excluded in acute rejection
      periods and when the serum creatinine levels were above 2.5 mg/dL, representing
      chronic allograft nephropathy. Concurrently recorded serum C0 and C2 levels were
      present for only 21 patients. Overall, we evaluated the records of 245 visits for
      these 21 patients. The incidence of hyperlipidemia decreased in the late
      posttransplant period, being significant for hypercholesterolemia. C2 had strong
      negative correlation with serum lipids; it was significant for total cholesterol
      in the early posttransplant period (r=-0.542, P=.005), but weaker in the late
      posttransplant and whole posttransplant periods. Thus correlation of C2 with
      serum lipids showed differences during posttransplant follow-up. C0, on the other
      hand, was positively correlated with total cholesterol levels in all periods,
      being significant for the whole posttransplant period (r=0.293, P=.000) and for
      the late posttransplant period (r=0.196, P=.025). Although not statistically
      significant, C0 levels were higher among hypertriglyceridemic or
      hypercholesterolemic episodes both in the early and the late posttransplant
      periods. When only the C0 levels of all 25 patients were analyzed (789 visits),
      C0 and serum cholesterol levels were positively correlated both in the early and
      the late posttransplant periods (P=.013, r=0.198 and P=.000, r=0.177,
      respectively). We concluded that C0 has a more predictable correlation with serum
      cholesterol levels after renal transplantation in adolescent patients.

PMID- 16797284
TI  - The effect of MDR1 (ABCB1) polymorphism on the pharmacokinetic of tacrolimus in
      Turkish renal transplant recipients.
AB  - There is marked interindividual variability in trough blood levels of tacrolimus
      (TRL) following standard dosing. TRL is a substrate for P-glycoprotein (P-gp),
      the product of the multidrug resistance-1 (MDR1)(ABCB1) gene. P-gp acts as a
      membrane efflux pump, which affects TRL absorption from the gut. Some of the
      single nucleotide polymorphisms (SNP) of ABCB1 gene are associated with
      pharmacokinetic characteristics of TRL. The objective of this study was to
      determine the role of ABCB1 C3435T polymorphism on TRL dose requirements, trough
      values and dose-adjusted trough TRL concentrations among Turkish renal transplant
      recipients. Renal transplant recipients receiving TRL (n=92) were genotyped for
      ABCB1. TRL daily doses, trough concentrations, dose-adjusted trough
      concentrations, demographic features, and clinical data were obtained at 1, 6,
      and 12 months after renal transplantation. The frequency of the ABCB1 3435 CC
      genotype was 30.4%, whereas 47.8% of patients were 3435 CT and 21.7% of patients
      were 3435 TT. TRL daily doses were significantly lower among patients with the
      3435 TT genotype at months 1 and 6. At 6 and 12 months after transplantation
      patients who were homozygous for the ABCB1 3435 CC showed significantly lower
      dose-adjusted trough TRL concentrations compared with subjects of 3435 TT and CT
      genotypes. Knowledge of ABCB1 genotype may be useful to adjust the optimal dose
      of TRL in transplant patients, thereby rapidly achieving target concentrations.

PMID- 16797285
TI  - Switching from cyclosporine to tacrolimus leads to improved disease-specific
      quality of life in patients after kidney transplantation.
AB  - BACKGROUND: Advances in transplantation medicine are linked to improved efficacy
      of immunosuppressive agents. At the same time, these agents endanger medical
      success by side effects that may impair survival and quality of life (QOL). This
      study examined whether conversion to tacrolimus-based immunosuppression due to
      cyclosporine-related side effects improved. QOL in patients after kidney
      transplantation. METHODS: In total 64 patients (29 men) with an average age of 51
      years (SD+/-12) who had received a kidney allograft an average of 5.6 years (SD+/
      4) before conversion participated. The reasons for conversion were
      cardiovascular/metabolic (n=26) or periodontal/dermatological side effects (n=38)
      of cyclosporine therapy. QOL was assessed before conversion and in average 7
      months thereafter by a global (SF-36) and a disease-specific instrument (ESRD
      SCL). RESULTS: Disease-specific QOL (ESRD-SCL, global index) improved
      significantly (P<.001, explanation of variance [EV]=16.6%) after conversion from
      cyclosporine to tacrolimus. In detail, cardiac and renal dysfunction (P<.01,
      EV=12.9%) as well as increased growth of gum and hair (P<.0001, EV=53.2%) were
      significantly reduced at end of the study. However, global QOL (SF-36) remained
      unchanged. CONCLUSION: Regardless of the indication (cardiovascular or cosmetic),
      switching to tacrolimus due to cyclosporine-related side effects improved disease
      specific QOL within the short term.

PMID- 16797286
TI  - Conversion from calcineurin inhibitors to sirolimus in patients with chronic
      renal allograft dysfunction.
AB  - BACKGROUND: Chronic renal transplant dysfunction in part may be due to the
      nephrotoxic effects of calcineurin inhibitors, which are still the mainstay of
      immunosuppressive therapy. Sirolimus, a new immunosuppressive compound devoid of
      significant nephrotoxicity, might therefore exhibit beneficial effects when used
      in renal transplant recipients with graft dysfunction. METHODS: Twelve renal
      transplant recipients included in this study had all been receiving calcineurin
      inhibitors for more than 12 months, and were free of rejection for more than 12
      months. However, they demonstrated moderate renal dysfunction with serum
      creatinine values ranging from 1.8 to 4.0 mg/dL (164 to 351 micromol/L). After
      reaching a sirolimus level of 10 to 20 ng/mL, calcineurin inhibitor therapy was
      withheld. RESULTS: One month after initiation of sirolimus therapy, all patients
      were off calcineurin inhibitors. The average daily sirolimus dosage was 5.8+/-3.4
      mg. No acute rejection episode and no graft failure was observed. No patient
      required hemodialysis or admission to the hospital. Calculated creatinine
      clearance increased from 63.4+/-9.9 to 69.2+/-9.7 mL/min (P=.0368) and serum
      bicarbonate increased from 20.8+/-3.17 to 22.5+/-3.7 meq/L (P=.001). Serum
      cholesterol increased from 180+/-26.5 to 239+/-28.8 mg/dL (4.65+/-0.69 to 6.18+/
      0.74 mmol/L, P<.001), triglycerides increased from 155+/-53 to 289+/-123 mg/dL
      (1.75+/-0.6 to 3.26+/-1.39 mmol/L) and low-density lipoprotein cholesterol
      increased from 99+/-32 to 131+/-25.1 mg/dL (2.56+/-0.83 to 3.39+/-0.65 mmol/L,
      P=.01). Arterial blood pressure remained well controlled (126+/-15.6/74+/-8.9 vs
      134+/-16.8/83+/-9.7). CONCLUSION: Conversion from calcineurin inhibitor therapy
      to sirolimus in patients more than 1 year after transplantation with impaired
      organ function is feasible, safe, and associated with a trend toward improved
      renal function.

PMID- 16797287
TI  - Sirolimus-induced intractable chronic diarrhea: a case report.
AB  - Sirolimus is a macrolide that is extensively used in transplant clinics. The most
      common side effects of sirolimus are hypertriglyceridemia, hypercholesterolemia,
      hypertension, rash, and well-tolerated diarrhea. Herein I have reported a case of
      intractable, disabling, chronic diarrhea secondary to sirolimus in a renal
      transplant recipient. The sirolimus dose had been recently increased from 2 mg to
      5 mg 1 month before the patient began to complain of severe diarrhea. In addition
      to the case presentation, the literature is reviewed as well as possible
      mechanisms of sirolimus-induced diarrhea are discussed. In conclusion, clinicians
      should consider sirolimus as a potential etiology for severe chronic diarrhea
      among patients who are treated with sirolimus.

PMID- 16797288
TI  - Efficacy and safety of enteric-coated mycophenolate sodium (myfortic) in de novo
      renal transplant recipients: results of a 12-month multicenter, open-label,
      prospective study.
AB  - Enteric-coated mycophenolate sodium (EC-MPS) has been developed as an alternative
      formulation of mycophenolate acid aiming for improved gastrointestinal (GI)
      tolerability. This 12-month, open-label, multicenter, prospective study
      investigated the efficacy and tolerability of EC-MPS (720 mg twice a day) given
      in combination with cyclosporine microemulsion (CsA-ME) in de novo renal
      transplant recipients (n=140). The efficacy evaluation was the incidence of
      treatment failure (defined as biopsy-proven acute rejection [BPAR], graft loss,
      or death) after 6 and 12 months of treatment. The incidences of treatment
      failure, BPAR, and graft loss were comparable at 6 and 12 months (18.6% vs 22.1%,
      15.7% vs 19.3%, and 1.4% vs 2.1%, respectively). Renal function at 6 and 12
      months (creatinine clearance) was 60.6+/-19.8 mL/min and 63.2+/-27.1 mL/min,
      respectively. EC-MPS was generally well tolerated; 95.9% of the reported GI
      adverse events (AEs) were rated as mild or moderate. The rate of EC-MPS dose
      reduction was 26.4%; 4.3% were due to GI AEs. The rate of EC-MPS dose
      interruption was 10%; 2.1% were due to GI AEs. In summary, EC-MPS given in
      combination with CsA-ME demonstrates good efficacy and tolerability in de novo
      renal transplant recipients.

PMID- 16797289
TI  - Acute rejection risk in kidney transplant recipients on steroid-avoidance
      immunosuppression receiving induction with either antithymocyte globulin or
      basiliximab.
AB  - Immunosuppression with rapid discontinuation of corticosteroids, usually with
      induction therapy, is safe in kidney transplant recipients. In 89 patients, we
      induced immunosuppression with basiliximab or rabbit antithymocyte globulin (17
      and 72 patients, respectively). Selection criteria for basiliximab were age
      (>or=65 years), history (malignancy; chronic infection), and type 1 diabetes
      mellitus (eligible for pancreas transplant). Steroids were administered through
      posttransplantation day 4 (five doses); maintenance immunosuppression was with
      tacrolimus and mycophenolate mofetil. At last follow-up (average, 286 days), most
      patients were steroid-free (antithymocyte globulin, 90%; basiliximab, 88%).
      Protocol biopsies were performed at 1, 4, and 12 months posttransplantation. The
      overall risk of biopsy-proven acute rejection was 12%. At 6 months
      posttransplantation, acute rejection-free survival was 93% for antithymocyte
      globulin, 65% for basiliximab (P<.001). Median time to biopsy-proven acute
      rejection was 27 and 71 days, respectively. The low incidence of biopsy-proven
      acute rejection with steroid-avoidance immunosuppression may be further reduced
      with antithymocyte globulin.

PMID- 16797290
TI  - Urinary transforming growth factor-beta-induced gene-h3 (betaig-h3) as a
      sensitive predictor in chronic cyclosporine nephrotoxicity.
AB  - Transforming growth factor (TGF)-beta is involved in the pathogenesis of chronic
      cyclosporine nephrotoxicity (CyAN). Since the expression of TGF-beta induced gene
      h3 (betaig-h3) is up-regulated by TGF-beta, we evaluated the potential role of
      betaig-h3 as a sensitive urinary marker to monitor the progression/regression of
      chronic CyAN. Urinary betaig-h3 levels were determined using an enzyme-linked
      immunosorbent assay in nine patients with chronic CyAN and 13 patients with
      stable graft function. We scored the extent of tubulointerstitial fibrosis (TIF)
      and using immunoperoxidase labeling, determined betaig-h3 expression in renal
      tissues of patients with chronic CyAN. Urinary betaig-h3 excretion was higher in
      chronic CyAN compared to control subjects (173.4+/-26.0 vs 62.6+/-5.0 ng/mg
      creatinine, P<.01). In chronic CyAN, the degree of TIF correlated with increased
      urinary betaig-h3 levels (r=.785, P<.05). In kidneys with chronic CyAN, betaig-h3
      labeling was more prominent at the basement membranes (BM) of the tubules where
      inflammatory cells had infiltrated the surrounding interstitium. Moreover, the BM
      of the atrophied tubules and their surrounding interstitium were strongly
      labeled. Urinary betaig-h3 levels decreased from 173.4+/-26.0 to 64.9+/-14.4
      ng/mg creatinine at 1 month after discontinuation of CyA or reduction in CyA
      dosage (P<.01) despite unchanged serum creatinine levels. Urinary betaig-h3
      levels increased in patients with chronic CyAN and decreased after
      discontinuation or reduction of CyA dosage. Our results suggested that urinary
      betaig-h3 levels could be used as a sensitive urinary marker to monitor the
      progression or regression of chronic CyAN.

PMID- 16797291
TI  - Tacrolimus-associated hypomagnesemia in renal transplant recipients.
AB  - BACKGROUND: Since hypomagnesemia occurs frequently in tacrolimus treated
      patients, we studied the correlation between renal magnesium wasting and
      tacrolimus blood levels in renal transplant patients. METHODS: Serum magnesium,
      fractional excretion of magnesium (FEMg), and 24-hour urinary excretion of
      magnesium were measured in 41 transplant patients and 10 healthy volunteers for
      correlation with tacrolimus level. RESULTS: Of tacrolimus-treated patients, 43%
      displayed hypomagnesemia. FEMg (7.42+/-3.59% versus 1.88+/-0.43%) and 24-hour
      urinary excretion (112.36+/-51.43 mg/dL versus 6.7+/-2.79 mg/dL) were
      significantly higher among tacrolimus-treated patients than controls. Magnesium
      replacement did not influence FEMg or 24-hour urinary magnesium excretion.
      Tacrolimus level was the best predictor of 24-hour urinary magnesium excretion
      and FEMg. Serum magnesium levels correlated inversely with tacrolimus
      concentrations and creatinine clearance. CONCLUSION: Hypomagnesemia in renal
      transplant recipients results from renal magnesium wasting. Tacrolimus levels and
      renal function impact on the excess renal magnesium excretion. Studies of longer
      duration are warranted to assess the long-term effects of this early
      posttransplant hypomagnesemia.

PMID- 16797292
TI  - The impact of daily sodium intake on posttransplant hypertension in kidney
      allograft recipients.
AB  - INTRODUCTION: Posttransplant hypertension is a well-known risk factor for long
      term allograft failure and mortality in kidney recipients. Although dietary
      sodium restriction is a widely recommended nonpharmacological measure for control
      of blood pressure (BP), no detailed investigation has been conducted regarding
      the impact of dietary sodium restriction on this condition. METHODS: Thirty-two
      patients on antihypertensive treatment completed the study. They were randomly
      divided into two groups: controls (group 1) versus strict sodium diet (group 2;
      80 to 100 mmol sodium daily). After randomization, 24-hour urine for sodium
      measurement, BP, and allograft functions were recorded at baseline and after 3
      months. BP treatment was reevaluated at each visit throughout the study. RESULTS:
      At baseline, there was no significant difference in age, sex, serum creatinine,
      systolic and diastolic BP, antihypertensive drugs, or 24-hour urinary sodium
      levels between the groups. After 3 months, daily urinary sodium excretion (from
      190+/-75 to 106+/-48 mEq/d, P<.0001), systolic BP (from 146+/-21 to 116+/-11 mm
      Hg), and diastolic BP (from 89+/-8 to 72+/-10 mm Hg) had significantly decreased
      in group 2, while no significant changes were observed in group 1. CONCLUSION:
      Low sodium intake in combination with antihypertensive treatment appears to
      efficiently control BP in kidney allograft recipients with hypertension. Twenty
      four-hour urinary sodium excretion should be checked regularly in these patients
      as a useful marker to indicate whether the patient complies with low sodium
      intake.

PMID- 16797293
TI  - Angiotensin-converting enzyme gene polymorphism in chronic allograft nephropathy.
AB  - Angiotensin causes an increased activity of hypertrophic and fibrotic processes,
      which similarly develop in the walls of small vessels of a renal graft during
      chronic rejection. In this context, the angiotensin-converting enzyme (ACE) gene,
      associated with increased angiotensin production, has been the subject of studies
      on renal diseases. The present study evaluated the influence of the ACE gene
      deletion polymorphism in chronic allograft nephropathy. We evaluated 240 renal
      transplant recipients including, 119 with normal renal function and 121 with
      chronic allograft nephropathy. The polymorphism was determined by polymerase
      chain reaction and genotyping performed after electrophoresis in 1.5% agarose
      gels stained with ethidium bromide. The frequency of the polymorphic allele was
      similar in both groups of patients. Furthermore, no significant effect of
      genotype was observed in chronic allograft nephropathy. Therefore, in this study,
      we observed no influence of the ACE gene polymorphism in chronic allograft
      nephropathy.

PMID- 16797294
TI  - Does cyclosporine have a beneficial effect on the course of chronic hepatitis C
      infection after renal transplantation?
AB  - The aim of our study was to assess the long-term liver histology in renal
      transplant patients infected with hepatitis C virus (HCV) who were treated with a
      cyclosporine-based regimen. Among 55 anti-HCV+/RNA+ patients, liver biopsies (LB)
      were requested every 3 to 4 years after transplantation: two LBs (n=55); three
      LBs (n=44); four LBs (n=10). Overall, the rate of liver fibrosis progression was
      0.07+/-0.03 Metavir U/y. Only three patients out of 55 (5.4%) developed
      cirrhosis. Liver fibrosis remained stable throughout follow-up in 21 patients;
      increased in 21 patients; and improved in the remaining 13 patients. The
      incidence of posttransplant diabetes mellitus was low (9%). We concluded that HCV
      infection is not harmful to liver histology in more than 50% of renal transplant
      patients with grafts functioning more than 6 years. Cyclosporine might have
      beneficial effects on the natural course of HCV infection after renal
      transplantation.

PMID- 16797295
TI  - Scedosporium apiospermum soft-tissue infection: a case report and review of
      kidney transplant literature.
AB  - Scedosporium apiospermum is an environmental mould. Human infections caused by
      this organism have been observed; however, only a few case reports show its role
      as a telluric contaminant to kidney recipients. We have reported here a case of a
      dramatic soft tissue infection by S. apiospermum in a kidney-transplanted man.
      Surgical drainage together with voriconazole systemic therapy was successful.

PMID- 16797296
TI  - Persistent mediastinal and axillary lymph node tuberculosis in a renal transplant
      patient with successful outcome.
AB  - Tuberculosis is an opportunistic infection that carries substantial morbidity and
      mortality in renal transplant recipients. We report here about a 21 year-old man
      with a living related renal transplant from his mother who developed persistent
      extra-pulmonary tuberculosis. The disease showed aggressive invasion to the
      axillary and mediastinal regions with abscess formations, despite standard
      antituberculosis treatment. During the course of the disease, immunosuppressive
      therapy was stopped, and the patient received extraordinary doses of multiple
      antituberculosis drugs. The patient then showed an uneventful course with good
      clinical and radiological responses.

PMID- 16797297
TI  - Isolated hepatic tuberculous abscess in a renal transplant recipient.
AB  - Tuberculous liver abscess is rare worldwide. We report a 26-year-old renal
      transplant recipient who presented with fever, fatigue, and weight loss.
      Ultrasound (US) of the abdomen showed a cystic mass of 7x6 cm in the subcapsular
      region of right liver lobe. US-guided percutaneous drainage was performed and 100
      mL of yellow-colored pus was aspirated. The patient was empirically started on
      ampicillin sulbactam treatment. Despite this treatment, the symptoms persisted.
      Subsequent control abdominal US showed the persistence of a cystic mass of 7x6 cm
      with thin septation in the subcapsular region near the right liver lobe, which
      were subsequently diagnosed as a focal hepatic tuberculous abscess by positive
      culture in Lowenstein-Jensen medium. He was concomitantly started on systemic
      antituberculous therapy. A tuberculous liver abscess must be considered in the
      differential diagnosis. Percutaneous drainage along with systemic antituberculous
      chemotherapy must be considered as an alternative to surgery for the management.
      A greater awareness of this clinical entity is required for successful treatment.

PMID- 16797298
TI  - Mycobacterium tuberculosis infection in renal transplant recipients.
AB  - Mycobacterium tuberculosis (TB) infection is more common among renal allograft
      recipients compared with the general population due to immunosuppression. The
      epidemiological risk in a country is an important determinant of transplant TB
      after transplantation. We retrospectively analyzed 283 renal transplant
      recipients who underwent renal transplantation between 1990 and 2004. We
      evaluated the incidence, patient and disease characteristics, prognosis, and
      outcome of TB infection. Tuberculosis developed in 10 (seven men and three women
      of mean age of 41+/-9 years) among 283 patients (3.1%). All patients were culture
      positive for M tuberculosis. Although pulmonary TB was the most common
      presentation in the general population, 50% of patients in the study group
      developed extrapulmonary TB. The mean elapsed time from renal transplantation was
      38 months. Three patients (1%) developed TB in the first year after
      transplantation. All patients were treated with a quartet of anti-TB therapy. One
      patient developed isoniazid-related reversible hepatotoxicity. No acute allograft
      rejection occurred during the anti-TB therapy. Two patients (20%) with pulmonary
      TB died due to dissemination of the disease. In conclusion, extrapulmonary
      presentations of TB are more common among renal transplant recipients with the
      increased risk of mortality.

PMID- 16797299
TI  - Systemic herpes simplex virus infection following cadaveric renal
      transplantation: a case report.
AB  - Herpes simplex virus (HSV) infection usually occurs in immunocompromised or
      severely debilitated patients. It is not so common in patients with renal
      transplants. The diagnosis can only be made histologically. It usually occurs
      during or shortly after treatment of graft rejection with high-dose steroids. We
      have recently experienced a case of HSV esophagitis and nephropathy in the renal
      allograft biopsy, which was identified by histology, immunostaining, and electron
      microscopy. A 43-year-old woman underwent cadaveric renal transplantation with
      cyclosporine and prednisolone treatment. Twelve months later, she developed renal
      insufficiency and proteinuria. Allograft renal biopsy showed some evidence of
      acute rejection. She was treated with 3 successive days of methylprednisolone
      (1.0 g/d) intravenously and continued tapering of steroids. Three weeks after
      steroid pulse therapy, she had throat pain, oral cavity ulcer, dysphagia, and
      febrile sensation. Esophagoscopy revealed multiple confluent ulcers in the whole
      esophagus, and biopsy showed enlarged epithelial cells with prominent nuclei.
      Immunohistochemically, the epithelial cells were positive with a monoclonal
      antibody to HSV type 1. She was started on acyclovir intravenously, which was
      continued for a week. After a week, her symptoms began to improve and repeat
      endoscopy showed no residual esophagitis. A renal allograft infection with HSV
      can persist in heavily immunosuppressed patients with recurrent rejection
      episodes. HSV mainly affects tubular cells causing necrosis, a major reason for
      functional deterioration. A biopsy is required for diagnosis.

PMID- 16797301
TI  - Respiratory problems in renal transplant recipients admitted to intensive care
      during long-term follow-up.
AB  - Cardiovascular disease, malignancies, and infectious complications are major
      causes of morbidity and mortality of renal transplant recipients. Mortality rates
      vary between 16% and 40% in an intensive care unit (ICU). The aims of this study
      were to identify the types incidences of respiratory problems that affected renal
      transplant recipients admitted to the ICU during long-term follow-up thereby
      determining the impact of respiratory problems on mortality. We reviewed the data
      for 34 recipients who had 39 ICU admissions from January 2000 through December
      2003. Twenty-four admissions (61.5%) had at least one respiratory problem at
      admission or developed at least one during the ICU stay. The most frequent
      problem was pneumonia (n=18, 46.2% of the 39 readmissions), followed by acute
      respiratory failure (n=10, 25.6%), atelectasis (n=9, 23.1%), pleural effusion
      (n=8, 20.5%), and pulmonary edema (n=2, 5.1%). The patients who had respiratory
      problems showed a significantly higher mortality rate than those who did not have
      respiratory problems (66.6% versus 26.6%, respectively; P<.05). The overall
      mortality rate was 58.8% (20 patients). Thus, infectious and respiratory problems
      are the most frequent indications for admission and the most common problems
      during an ICU stay. The prognosis for patients who either have a respiratory
      problem upon admission to the ICU or develop one during the ICU stay is poor.

PMID- 16797300
TI  - Opportunistic posterior uveal infections in renal transplant patients.
AB  - AIMS: To describe the cases of opportunistic posterior uveal infection diagnosed
      in renal transplant recipients at a single center over a 10-year period. METHODS:
      The study involved 1156 patients who underwent renal transplantation. Five of the
      recipients were diagnosed with posterior uveal infection. The specific diagnoses
      were acute retinal necrosis (two cases), cytomegalovirus retinitis (one case),
      nocardial chorioretinitis (one case), or tuberculoid granuloma (one case).
      RESULTS: The five patients were aged 27 to 55 years, and the interval from renal
      transplantation to uveal infection ranged from 7 months to 16 years. All patients
      were receiving immunosuppressive treatment at the time of the posterior uveal
      infection. Acute retinal necrosis was diagnosed in cases I and II at 2 and 3
      years after transplantation, respectively. In both cases, fundus examination
      revealed moderate vitritis and yellow-white lesions representing confluent
      retinitis. In case III (cytomegalovirus retinitis), 7 months after
      transplantation the patient developed extensive hemorrhage and confluent white
      exudates, periphlebitis, and perivascular sheathing in the right eye. In case IV,
      culture of a fine-needle aspirate from a well-demarcated, white-yellow, elevated
      choroidal lesion in the superotemporal region of the macula revealed nocardial
      infection. Fundus examination of the right eye of case V revealed a small,
      hypopigmented choroidal lesion superior to the optic disc. The lesion was
      identified as a choroidal tuberculoid granuloma. CONCLUSIONS: Opportunistic
      chorioretinal infections can occur at any time after renal transplantation. So it
      is important that every kidney recipient undergo regular ophthalmic examinations
      throughout his or her lifetime.

PMID- 16797302
TI  - Postural epigastric pain as a sign of CMV gastritis: a case report.
AB  - Cytomegalovirus (CMV) infection is a common cause of morbidity and mortality
      among patients receiving chronic maintenance immunosuppression and is often
      considered the most important infection in renal transplantation. CMV gastritis
      has been reported in transplant patients. We present a case of CMV gastritis with
      epigastric pain that decreased in supine position, increased while sitting, and
      further increased when standing or walking. To our knowledge this is the second
      article presented to the literature so far.

PMID- 16797303
TI  - Nephron-sparing surgery for renal tumor: a choice of treatment in an allograft
      kidney.
AB  - The incidence of de novo malignancies is an accepted complication of organ
      transplantation. Renal cell carcinoma (RCC) was 4.6% of cancers occurring de novo
      in organ allograft recipients compared with 3% in the general population. Less
      than 10% of these renal cancers affected the renal allograft. Among patients
      developing a renal tumor in the kidney allograft, transplant nephrectomy reduced
      the quality of life. For these patients for whom preservation of renal function
      is a relevant clinical consideration, partial nephrectomy may be considered the
      choice for treatment. Fifteen cases have been reported regarding conservative
      surgery on kidney transplant tumors. Herein we have reported three cases of renal
      masses in well-functioning kidney transplants that were successfully treated with
      nephon-sparing surgery. Our experience demonstrated that in selected patients,
      nephron-sparing surgery on a renal allograft represents a feasible approach for
      tumor removal with preservation of graft function.

PMID- 16797304
TI  - Conservative surgical treatment of low-grade urothelial carcinoma in the renal
      allograft recipient: a case report.
AB  - Development of urothelial carcinoma in a renal allograft is rare. We report the
      case of 52-year-old male patient who developed chronic renal failure secondary to
      Balkan endemic nephropathy and underwent renal allotransplantation. The patient
      who developed low-grade pTa urothelial carcinoma in the left contracted kidney at
      3 years after transplantation and underwent nephroureterectomy. Three years
      later, the same neoplastic process was observed in the renal allograft.
      Preoperative estimation for allograft tumor recurrence and progression included
      percutaneous tumor biopsy followed by cytopathological, histological, and
      cytogenetic analysis. Cytopathology revealed well-differentiated urothelial tumor
      cells. Histopathologic analysis showed low-grade urothelial carcinoma.
      Cytogenetic examination demonstrated that the tumor originated from the recipient
      suggesting a low malignant potential of carcinoma. Based on these findings, we
      decided to perform a right-side nephroureterectomy and graft-sparing procedure,
      which resulted in preservation of allograft function. In this report we discussed
      the prognostic factors, which are the basis for rational therapeutic approaches
      in these patients.

PMID- 16797305
TI  - Oral retinoids for chemoprevention of skin cancers in organ transplant
      recipients: results of a survey.
AB  - Systemic retinoid therapy is thought to be beneficial for chemosuppression of
      skin cancers in solid organ transplant recipients. We present the results of a
      survey of 28 dermatologists with experience managing transplant recipients to
      clarify when and how systemic retinoids are used in this population. Almost 80%
      of respondents use retinoids in some transplant recipients. Factors influencing
      the use of retinoids include the incidence and aggressiveness of cutaneous
      squamous cell carcinomas and the extent of concomitant actinic keratoses.
      Patients are monitored more closely during periods of dose adjustment than during
      the maintenance phase of therapy. Adverse effects are variably managed
      symptomatically, with dose adjustment, by discontinuation of retinoids, or by
      referral to another specialist for further evaluation. In the absence of large
      randomized controlled trials, the practice habits of experienced physicians serve
      as a useful guide for the use of oral retinoids in transplant recipients.

PMID- 16797306
TI  - An unusual case of port site metastasis after laparoscopic cholecystectomy in a
      renal transplant patient: a case report.
AB  - Port site metastasis after laparoscopy is a rarely seen intraabdominal malignancy
      independent of tumor stage. We present an unusual case of port site
      adenocarcinoma metastasis from unknown origin following laparoscopic
      cholecystectomy. A 52-year-old woman with a previous renal transplant underwent a
      laparoscopic cholecystectomy for symptomatic cholelithiasis. Six months later,
      she was admitted to the hospital with a complaint of a mass at the four trocar
      sites. A biopsy from the port sites led to the diagnosis of adenocarcinoma
      metastasis. Port site metastasis after laparoscopic cholecystectomy is seen
      especially after gallbladder cancer, and less frequently after intraabdominal
      malignancy independent of tumor stage. Our patient illustrated that port site
      metastasis probably spread from an undetected cancer site of an early stage
      intraabdominal tumor. Immunosuppression may have increased the likelihood of
      tumor seeding at the port sites.

PMID- 16797307
TI  - Short-term administration of ACTH improves plasma lipid profile and renal
      function in kidney transplant patients.
AB  - The present study investigated effects of short-term administration of
      adrenocorticotrophic hormone (ACTH) on blood lipid profile and renal function in
      kidney transplant patients. Six patients who had kidney transplantations 2 to 10
      years earlier received ACTH intramuscularly (1 mg/d) for 4 days. We analyzed
      serum levels of lipids, lipoproteins, apolipoproteins, blood creatinine, and
      other parameters. Short-term ACTH treatment significantly decreased serum
      apolipoprotein B and apolipoprotein AI, whereas it significantly increased plasma
      high-density lipoproteins (HDL). Interestingly, creatinine level moderately
      decreased and creatinine clearances moderately increased among five of six
      patients. Hepatic function and serum concentration of cyclosporine did not
      change. There were no serious side effects during ACTH treatment. It was
      concluded that ACTH treatment had beneficial effects on serum lipoprotein
      profile, potentially improving renal function in kidney transplant patients.
      Further observations are needed to confirm these effects.

PMID- 16797308
TI  - Biopsy-related hemorrhage of renal allografts treated by percutaneous
      superselective segmental renal artery embolization.
AB  - INTRODUCTION: Biopsy-related vascular injuries in renal transplants are rare, but
      they can lead to dramatic clinical symptoms prompting immediate treatment.
      Transcatheter embolization is a minimally invasive technique used to treat some
      forms of arterial bleeding. This study evaluated the efficacy of this technique
      in iatrogenic biopsy-related vascular lesions in renal allografts. MATERIALS AND
      METHODS: Over the last eight years, six patients with severe renal hemorrhage
      were admitted to the angiography department of our hospital for evaluation and
      possible further treatment. All of them had a history of previous biopsy of a
      transplanted kidney. They all presented with clinical signs of hemodynamic
      instability. Angiographic investigation of the kidneys preceded further
      intervention in all cases. All underwent hyperselective embolization of the
      specific bleeding vessel with the use of microcoils and/or gelfoam particles.
      RESULTS: Successful embolization of the feeding artery could be performed in all
      patients. Superselective segmental renal artery embolization had a successful
      outcome concerning a steady renal function and a stable clinical course. No
      complications occurred. CONCLUSION: Transcatheter embolization is a safe and
      efficient endovascular technique to treat biopsy-related vascular injuries in
      renal transplants. Immediate clinical success and significant benefit in renal
      function can be obtained, and the longevity of the allograft after successful
      embolization mainly depends on the natural outcome.

PMID- 16797309
TI  - Efficacy and safety of vardenafil in renal transplant recipients with erectile
      dysfunction.
AB  - Erectile dysfunction (ED) profoundly affects the quality of life. The prevalence
      of ED in renal transplant recipients is reported by high as 50% to 60%. We
      evaluated the efficacy and safety of vardenafil in these patients with ED as well
      as its effects on graft function and on cylosporine or tacrolimus concentrations.
      Thirty-nine recipients with ED and serum creatinine values<2 mg/dL were treated
      with vardenafil. ED was assessed using the self-administered International Index
      of Erectile Function (IIEF). ED was diagnosed by using penile color-Doppler
      ultrasonography and intracavernosal injection. Vardenafil efficacy was assessed
      by readministering the IIEF questionnaire after 4 weeks of therapy. Serum
      creatinine levels, creatinine clearances, and cyclosporine/tacrolimus
      concentrations were measured before and after vardenafil therapy. Twenty-one
      recipients with ED served as placebo controls and 15 without ED as another
      control group. The IIEF scores improved from 12.80+/-3.5 to 26.46+/-2.4 in
      vardenafil-treated patients with ED (P<.001). Renal function and
      cyclosporine/tacrolimus concentrations did not change with vardenafil therapy.
      Side effects were observed in 7 (18%) patients: headache in three, palpitations
      in one, flushing in two, and dyspepsia in one. This study demonstrated that ED
      improved with vardenafil in renal transplant recipients with ED. For 4 weeks
      vardenafil therapy was free of side effects. Renal function tests did not change.
      Also, no dose change in immunosuppressive drugs was required during 4 weeks of
      verdanafil therapy.

PMID- 16797310
TI  - Effects of cholesteryl ester transfer protein TAQ1B polymorphism in renal
      transplant patients.
AB  - BACKGROUND: Dyslipidemia is an important complication in renal transplant
      patients. Cholesteryl ester transfer protein (CETP) mediates the exchange of
      cholesteryl ester between high density lipoproteins and low density lipoproteins.
      The aim of this study was to investigate CETP Taq1B gene polymorphism and lipid
      abnormalities in renal transplant patients. METHODS: We studied 29 renal
      transplant patients and 29 healthy controls. CETP Taq1B polymorphism was
      determined by polymerase chain reaction and restriction fragment length
      polymorphism techniques. Serum lipid levels were measured enzymatically.
      Statistical analyses was performed by SPSS for Windows version 7.5. RESULTS: The
      frequencies of CETP Taq1B B1B1, B1B2, and B2B2 genotypes in patients were 44.8%,
      34.5%, and 20.7%; and in control subjects, 37.9%, 37.9%, and 24.2%, respectively.
      The patients with B1B1 genotype displayed higher levels of total cholesterol
      (TC), triglycerides, low density lipoprotein-cholesterol (LDL-C), very low
      density lipoprotein-cholesterol (VLDL-C), and diastolic blood pressure (DBP).
      (P<.05). Also, patients showing a B1 allele had higher levels of TC, LDL-C, VLDL
      C, and DBP compared to healthy controls (P<.05). CONCLUSION: We observed that
      CETP Taq1B B1 allele and B1B1 genotype have effects on the serum lipid profile
      among renal transplant patients.

PMID- 16797311
TI  - Can exchange transfusions treat postoperative intrahepatic colestasis in patients
      with sickle cell anemia?
AB  - BACKGROUND: Although the most common cause of liver failure (LF) in hematologic
      patients is viral hepatitis, several episodes of sickle cell intrahepatic
      cholestasis (IHC) have been reported as rare but potentially causative of
      fulminant LF. Reviewing the literature, we have presented a single case of
      intrahepatic cholestasis after major liver resection, which was effectively
      treated by exchange transfusion. METHODS: Serial hemoglobin S, D levels and liver
      enzymes were monitored postoperatively. RESULTS: Although the patient's intra-
      and postoperative courses were uneventful, an increased serum bilirubin was
      identified to be due to intrahepatic sinusoid congestion and subsequent
      cholestasis. Exchange transfusion was required to maintain HbS below 20% and
      reverse bilirubin levels to normal values. CONCLUSION: Sickle cell anemia is a
      rare cause of cholestasis after major hepatic surgery. To our knowledge, this
      case is the only documented incidence of IHC following major hepatectomy that was
      effectively treated with exchange transfusion.

PMID- 16797312
TI  - Intensive care unit management of fulminant hepatic failure.
AB  - OBJECTIVE: The aim of this open/retrospective study was to evaluate the outcomes
      of intensive care unit patients treated for fulminant hepatic failure (FHF) for
      predictive indices. METHODS: All patients were recovered in the intensive care
      units with a diagnosis of FHF. We considered three groups of patients: (1)
      survivors, deceased, and transplanted. SUBJECTS: All patients were fully
      screened, including liver function indices such as AST, ALT, total and bound
      bilirubin, albumin and pre-albumin, factors 5 and 7, alpha fetal protein (alpha
      PP), other coagulation tests (PT, aPTT, INR, ATIII), and renal function (BUN and
      creatinine) parameters. For each patient Apache II score was calculated upon
      admission to the intensive care unit. RESULTS: Apache II score showed efficacy.
      alpha-PP increased in both surviving and deceased, but not in the transplanted
      group. After intensive care unit admission, AST and ALT peaks were higher in the
      deceased DP than in the transplanted group. The INR value at the third day after
      ICU admission improved in the survivors compared with the other two cohorts.
      Factor 5 levels were lower among patients undergoing transplantation, but
      increased in the other two groups. The prognosis was strictly dependent upon the
      development of renal failure. CONCLUSION: The Apache II score was a sensitive
      predictive index for outcome. alpha-PP and factor 5 were not related to outcome,
      but useful for decision making when determining potential liver transplantation.
      INR can be used as a prognostic index. Intensive treatment beforehand is of
      primary importance to prevent multiple organ failure.

PMID- 16797313
TI  - Correlation between the radiologic and histologic size of hepatocellular
      carcinoma in patients eligible for liver transplantation.
AB  - Hepatocellular carcinoma is the most prevalent primary hepatic tumor. Early
      diagnosis and staging is of paramount importance to obtain favorable survivals.
      So far, there is no general agreement on the most appropriate imaging technique
      to detect the tumor for correlation between pretransplant radiologic and
      pathologic size of the tumor, which remains inadequate. With greater clinical
      experience and increasing accuracy of imaging methods, magnetic resonance (MR)
      appears to be the most accurate method, yielding a correlation in 67% of cases.

PMID- 16797314
TI  - Common peroneal nerve palsy: an unexpected complication of liver surgery.
AB  - BACKGROUND: Common peroneal nerve palsy is a well-recognized complication
      following surgery in lithotomy position, particularly colorectal and gynecologic
      surgery. But it is quite rare after liver surgery because patients are usually
      placed in supine position. CASE REPORT: There were three cases of common peroneal
      nerve palsy after liver surgery in the past 2 years, including two cases of liver
      transplantation and one case of extended right hepatectomy. Two cases were
      bilateral and one case was unilateral. They were placed in supine position and
      the mean operative time was 8 hours. Patients complained symptom of foot drop
      within 1 week after operation. Electromyographic examinations showed evidence
      compatible with common peroneal nerve palsy. All of them improved with
      conservative treatment within 6 months. CONCLUSION: Common peroneal nerve palsy
      may develop after liver surgery even in supine position. Injury to common
      peroneal nerve should be a concern before and during the operation. This
      complication could be managed conservatively with an uneventful result.

PMID- 16797316
TI  - Preoperative estimation of right lateral sector graft by three-dimensional
      computed tomography.
AB  - The right lateral sector is an alternative graft for living donor liver
      transplantation. Three-dimensional image reconstruction of right lateral sector
      grafts was performed to reveal vascular anatomy and volume using three
      dimensional computed tomography software in three donors. There was a correlation
      between actual and estimated volume (r=.93), although actual graft volume tended
      to be larger than the preoperative estimated volume. In one donor, a portal
      branch of the right lateral sector was independently ramified. The branch was
      sacrificed in the operation because its territory volume was only 44 cm3. Three
      dimensional images matched the shape of the right lateral sector graft. Three
      dimensional computed tomography might be useful before donor hepatectomy,
      providing important information for decisions regarding the operative procedure.

PMID- 16797315
TI  - Ascites, but not hyponatremia, is associated with high intraoperative transfusion
      and vasopressor requirements during liver transplantation.
AB  - BACKGROUND: We previously demonstrated that patients with high MELD scores
      required significantly higher volumes of blood transfusion and vasopressor usage
      during orthotopic liver transplantation (OLT) compared with patients with low
      MELD scores. Now we investigated whether hyponatremia or ascites were associated
      with increased transfusion and vasopressor requirements during OLT. METHODS:
      Medical records of 192 OLT patients between January 1, 2004, and May 5, 2005,
      were retrospectively reviewed. Intraoperative transfusion of red blood cells
      (RBC) or fresh frozen plasma (FFP) and administration of vasopressors were
      compared. RESULTS: As expected, patients with high (>30) MELD scores were
      associated with higher requirements for intraoperative transfusion and
      vasopressors than those with low (<or=30) MELD scores. Patients with or without
      hyponatremia (Na+> or <or=130) had similar requirements for transfusion and
      vasopressors. Patients with ascites had significantly higher requirements for
      both transfusion and vasopressors compared with those without (16.6+/-9.6 versus
      11.8+/-9.0 for RBC; 22.0+/-11.0 versus 16.1+/-11.8 for FFP; and 60.2% versus
      37.5% for vasopressors, P=.001 to .002). Patients with high (>30) MELD plus
      ascites scores (MELD+A, 4.5 points added to MELD if ascites was present) had
      higher requirements for transfusion and vasopressors compared with patients with
      low (<or=30) MELD+A scores (16.1+/-9.9 versus 11.4+/-8.6 for RBC; 21.7+/-12.7
      versus 15.2+/- 9.6; and 63.4% versus 28.2% for vasopressors, P=.001 to <.001).
      CONCLUSION: Although hyponatremia and ascites are indicators for liver disease
      severity, ascites, but not hyponatremia, is associated with increased
      intraoperative transfusion and vasopressor requirements during OLT.

PMID- 16797317
TI  - The role of hepatic biopsy to detect macrovacuolar steatosis during liver
      procurement.
AB  - The ability to predict graft function before transplantation has proven to be a
      difficult task, especially for macrovacuolar steatosis that is considered a major
      cause of posttransplant dysfunction. It is well known that macrovacuolar
      steatosis greater than 25% influences the short- and long-term outcomes of liver
      transplantation. We retrospectively analyzed frozen sections from 43 donor livers
      comparing preoperative laboratory/clinical values, and liver ultrasound of a
      cohort of donors without (group A, n=21) versus with steatosis of 25% to 35%
      (group B, n=22) upon liver biopsy performed during harvesting. We analyzed the
      possible correlations between preoperative donor data and the degree of
      macrovacuolar steatosis. None of the biochemical and clinical parameters were
      related to the degree of hepatic steatosis. The only difference between the two
      groups was the echographic pattern, with evidence of 27% fatty liver by
      ultrasound in group B and 5% in group A (p=.04). The specificity of hepatic
      ultrasound for macrovacuolar steatosis was 95% and the sensitivity was only 27%,
      while the positive and negative predictive value were 86% and 55%, respectively.
      In conclusion, liver biopsy during donor harvesting remains the gold standard to
      identify macrovacuolar steatosis greater than 25%. Hepatic ultrasound has a role
      to exclude the presence of steatosis in normal livers due to its high
      specificity, but it is not useful to make the diagnosis of a fatty liver since it
      has a low sensitivity and negative predictive value. Thereafter a liver
      ultrasound positive for hepatic steatosis alone should not be considered a
      valuable tool to discard an organ from transplantation.

PMID- 16797318
TI  - Risk factors for graft dysfunction after adult-to-adult living donor liver
      transplantation.
AB  - The aim of this study was to investigate the risk factors for graft dysfunction
      after adult-to-adult living donor liver transplantation (LDLT). Thirty-nine
      adults with chronic cirrhosis underwent LDLT between 1999 and 2004. Their
      postoperative courses were uneventful with no vascular or bile duct complications
      early after LDLT, except one mild hepatic artery stenosis. The preoperative MELD
      scores were significantly higher in the failed graft group (n=5) than the
      functioning graft group (n=34; P=.004), while the graft liver weight/standard
      liver volume ratio was similar between these groups. We concluded that a high
      preoperative MELD score was associated with postoperative graft failure and that
      graft size had little impact on graft outcome. Although large grafts would seem
      intuitively more suitable for sick recipients, we did not show a benefit among
      this cohort; the MELD score was the best predictor, a finding that is also most
      consistent with donor safety.

PMID- 16797319
TI  - Molecular mechanisms associated with donor-specific microchimerism in peripheral
      blood of Brazilian patients after liver transplantation.
AB  - A large number of studies in liver transplantation have demonstrated allogeneic
      microchimerism. The clinical and immunologic implications of this finding remain
      inconclusive, just as the influence of HLA mismatch and donor alloreactivity also
      are controversial. The present study analyzed the presence of allogeneic
      microchimerism in liver transplant recipients in relation to donor leukocyte
      kinetics and rejection episodes. The study was extended to determining the
      influence of immunogenetic factors in patients after liver transplantation. The
      presence of allogeneic microchimerism was analyzed on peripheral blood of 50
      recipients. DNA extracted from the samples was subjected to typing for HLA-DRB1
      and -DQB1 alleles by polymerase chain reactions using sequence-specific primers
      (PCR/SSP). Microchimerism was identified by nested PCR/SSP. Microchimerism was
      detected in 72% of patients. There was significant effect of microchimerism on
      rejection episodes (P=.002), while HLA mismatches did not show significance for
      one or two mismatches (P=.98). Allogeneic microchimerism detected in the majority
      of liver transplant patients was observed to be significantly associated with
      rejection episodes.

PMID- 16797320
TI  - Significance of C4d deposition in the diagnosis of rejection after liver
      transplantation.
AB  - C4d immunohistochemical staining of liver allograft biopsies was performed to
      assess its relationship to other pathological changes in the liver. C4d
      deposition was detected in 69.2% of liver graft biopsies from patients under
      going rejection, 33.3% of liver graft biopsies from patients with hepatitis B
      relapse after transplantation, and 28.6% of liver biopsies from patients with
      hepatitis B. When rejection occurred C4d deposition was located in the vascular
      walls of portal areas and hepatic sinusoidal walls. Examination of biopsies from
      patients with hepatitis B relapse after transplantation or hepatitis B infection
      showed C4d deposition only in the vascular walls of the portal area. C4d
      deposition in both vascular walls of portal area and hepatic sinusoidal walls was
      detected in only one of 12 ischemia-reperfusion damage cases. Repeated biopsy of
      the same patient 1 month later revealed acute cellular rejection. No C4d
      deposition was found in biopsies from a patient with bile duct occlusion after
      liver transplantation. C4d might serve as a sensitive marker for the diagnosis of
      liver rejection.

PMID- 16797321
TI  - Salvage procedure for unexpected portal vein thrombosis in living donor liver
      transplantation.
AB  - Portal vein thrombosis (PVT) is considered a relative contraindication to living
      donor liver transplantation (LDLTx) due to technical difficulty and ethical
      considerations. So far, there have been a few reported cases of LDLTx with PVT,
      most of which were treated by thrombectomy with or without a venous conduit. We
      report a case of LDLTx in an unexpected recipient with grade 4 diffuse PVT, which
      was successfully managed using a variceal left gastric vein and a deceased donor
      iliac vein conduit to create a "de novo portal vein" for splanchnic inflow to the
      right lobe. The patient experienced an uneventful postoperative course with
      normal blood flow in the de novo portal vein at 1-year follow up. This report
      demonstrated that a variceal collateral vein can be used as appropriate
      alternative inflow for the right lobe in LDLTx cases in which an unexpected PVT
      is encountered.

PMID- 16797322
TI  - Hemophagocytic syndrome after adult-to-adult living donor liver transplantation.
AB  - Hemophagocytic syndrome is a fatal complication after liver transplantation that
      is rarely reported. Among 260 adult patients who underwent living donor liver
      transplantation at our hospital, three cases (1%) were complicated with
      hemophagocytic syndrome. Intensive investigation revealed Aspergillus,
      cytomegalovirus, and hepatitis C virus as the most likely causative organisms in
      each patient. Despite the immediate initiation of anti-infectious treatment and
      supportive care, all patients died. When pancytopenia with possible underlying
      infectious disease is observed in liver transplant recipients, hemophagocytic
      syndrome should be suspected and bone marrow biopsy considered. The prognosis of
      hemophagocytic syndrome remains poor and further investigations are required to
      establish effective therapeutic options.

PMID- 16797323
TI  - Evaluation of pre- and posttransplantation serum interferon-gamma and soluble
      CD30 for predicting liver allograft rejection.
AB  - The aim of the present study was to identify whether the serum interferon-gamma
      (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of
      Th2 cytokine-producing T cells, predict acute cellular rejection episodes among
      liver graft patients. Pretransplant and posttransplant sera from 32 living donor
      liver transplant recipients obtained on days 1, 3, and 7 after surgery were
      tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked
      immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14)
      displayed significantly higher IFNgamma concentrations pretransplant than did the
      patients with no ARE (n=18) (P<.05). The pretransplant serum levels of sCD30 were
      not different between the non-ARE and ARE groups. However, in comparison with the
      non-ARE group, who showed steadily decreasing serum sCD30 levels after
      transplantation, 12 among the 14 patients in the ARE group showed increasing
      sCD30 levels from day 1 to day 3 after transplantation (P<.05). These results
      suggest that the sCD30 increment during the early period after liver
      transplantation affects the immune response of rejection. This observation
      emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma,
      as predictive markers for acute liver graft rejection.

PMID- 16797324
TI  - Liver transplantation of a child with child a cirrhosis and severe
      hepatopulmonary syndrome.
AB  - Hepatopulmonary syndrome (HPS) is a clinical state defined by a chronic hepatic
      disorder, intrapulmonary vascular dilatation, and altered gas exchange resulting
      in hypoxemia. Cirrhosis of the liver is the most common condition associated with
      HPS. A 3-year-old boy who presented with end-stage liver disease and severe
      hepatopulmonary syndrome underwent orthotopic liver transplantation (OLT). The
      findings of HPS resolved immediately after OLT. His status is within normal
      limits at 6 months after liver transplantation.

PMID- 16797326
TI  - Retransplantation of the liver.
AB  - Retransplantation (re-TX) is the only available therapy for irreversible liver
      graft dysfunction. The outcome of a second procedure depends upon several
      factors, some of which are not defined at the time of the decision to
      retransplant. This study is an analysis of all re-TX of the liver performed at
      our unit between January 1995 and January 2004. Among the 474 liver TX were 55
      (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2)
      indication for re-TX and time lapse; (3) donor age and cold ischemia time (CIT);
      (4) duration of operation, peroperative bleeding, and complications; (5) ICU and
      ward periods; and (6) patient and graft survivals. Patients who underwent re-TX
      did not differ from those transplanted once with regard to age, gender, or
      diagnosis. The indications for re-TX were roughly one-third biliary tract
      complications/chronic rejection, one-third hepatic artery thrombosis, and one
      third others, including primary nonfunction, acute rejection, portal vein
      thrombosis, sepsis, and B/C hepatitis. The re-TX were "urgent" in 29 and
      "elective" in 26 cases. Complications were common; about half of the patients
      were reoperated due to bleeding or biliary problems. To date (May 2004), 15
      patients have died (12 "urgent" and 3 "elective"), of whom 5 had well functioning
      grafts. In summary, liver re-TX is a complicated procedure associated with
      significant mortality and morbidity, but considering that the actual patient
      group has a poor prognosis without re-TX, the results are nevertheless
      encouraging.

PMID- 16797325
TI  - The incidence and management of acute and chronic rejection after living donor
      liver transplantation.
AB  - Living donor liver transplantation (LDLT) is a good alternative to cadaveric
      liver transplantation for end-stage liver disease. Herein we report the outcome
      of 132 LDLTs performed between 1999 and 2005, with special emphasis on the
      incidence and management of acute and chronic rejection. Among the LDLT
      population a first acute rejection episode (ARE) was clinically suspected in 24%
      and proven by liver biopsy in 11%. According to the Banff classification, 50% of
      AREs were grade 1, and 50%, grade 2. There was no grade 3 AREs. The first ARE
      occurred between 7 days and 23 months posttransplantation (mean 97 days, median
      70 days). Ninety-seven percent (31/32) of the AREs occurred within the first year
      after transplantation and 3% (1/32) in the second year. Among the patients with
      ARE, 23% developed a second ARE between 4 and 11 months. A third ARE was detected
      in 8% of patients after month 18. All AREs responded to adjustment of
      immunosuppressive doses or steroid boluses. Chronic rejection (CR) was detected
      in 2%. In conclusion, the incidences of ARE and CR are consistent with the
      previously reported data. Acute and chronic rejections seem to be mild and easily
      manageable clinical conditions. Our results also showed a significant difference
      between clinically suspected and biopsy-proven ARE emphasizing the importance of
      indicated liver biopsies in the management of the LDLT population.

PMID- 16797327
TI  - The impact of nonalcoholic fatty liver disease and the metabolic syndrome on
      progression of fibrosis in patients with recurrent HCV after liver
      transplantation.
AB  - Nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MS) have
      been shown to play a role in disease progression and response to therapy in
      patients with chronic hepatitis C virus (HCV) infection. The primary objective of
      this study was to evaluate the impact of coexisting NAFLD and MS on the
      progression of fibrosis in patients with recurrent HCV treated with interferon
      (IFN)/ribavirin after orthotopic liver transplantation (OLT). From 1998 to 2004,
      a total of 418 patients underwent OLT in our center for HCV-related cirrhosis.
      Thirty-five patients with recurrent HCV on IFN/ribavirin treatment, who had at
      least 2 posttransplant liver biopsies at least 6 months apart, were included in
      the study. Patients who had MS at the time of their first posttransplant biopsy
      were identified. The first and last posttransplant biopsies were assessed for the
      presence and severity of NAFLD, grade of inflammation, and stage of fibrosis. The
      fibrosis progression rate (FPR) was calculated and expressed in fibrosis units
      per month (FU/mo). Among 35 patients, 34% were diagnosed with NAFLD in the first
      posttransplant biopsy. The mean FPR was 0.05+/-0.16 FU/mo in the presence of
      NAFLD compared to 0.07+/-0.10 FU/mo in its absence (P=.68) and 0.03+/-0.06 FU/mo
      in the presence of MS versus 0.10+/-0.15 FU/mo in its absence (P=.06). When FPR
      values were divided into two categories of <0.16 FU/mo or >or=0.16 FU/mo
      (below/above the 25% upper quartile) or <0.08 FU/mo or >or=0.08 FU/mo
      (below/above the 50% upper quartile), there was no correlation between FPR
      categories and the presence of NAFLD with or without MS, only MS, or the absence
      of both in the first liver transplant biopsy (P=.13). Coexisting NAFLD or MS had
      no significant effect on the progression of fibrosis after OLT in patients with
      treated hepatitis C after OLT.

PMID- 16797328
TI  - Successful treatment of rhinomaxillary form of mucormycosis infection after liver
      transplantation: a case report.
AB  - Mucormycosis is a rare opportunistic infection, usually associated with
      immunocompromised states. Several conditions such as hematologic malignancy
      (leukemia, lymphoma, myeloma), solid organ transplantation, diabetes mellitus,
      corticosteroid therapy, or chemotherapy predispose patients to infection. The aim
      of this study was to present a single case of mucor infection after 900
      consecutive liver transplantations. Rhinomaxillary mucormycosis must be suspected
      in a transplant recipient showing fever, maxillary swelling, and edema. This
      condition can be successfully treated with early diagnosis and a combination of
      aggressive surgery and antifungal therapy.

PMID- 16797329
TI  - The prevention of bone fractures after liver transplantation: experience with
      alendronate treatment.
AB  - OBJECTIVE: The aim of this study was to prevent fractures in the first
      postoperative year. METHODS AND PATIENTS: We studied 59 patients (48 men, 11
      women) aged 42.6+/-11.4 years, who underwent liver transplantation. All patients
      received oral alendronate 70 mg weekly and calcium 1 g and calcitriol 0.5 mug
      daily. Bone mineral density (BMD) was measured by dual-energy X-ray
      absorptiometry at the lumbar spine and proximal femur at baseline as well as at 6
      and 12 months after transplantation for comparison with an historical control
      group (n=31). Spinal radiographs were obtained to assess vertebral fractures at
      the same time. Additionally, serum osteocalcin, serum parathyroid hormone (PTH),
      urinary deoxypyridinoline (DPD), and biochemical parameters were determined every
      3 months. RESULTS: At baseline, femoral total BMD of men was significantly
      greater than that of women (P<.05, .85+/-.1 vs .74+/-.1). A significant increase
      in BMD was observed at 12 months (P<.05), no patient developed a bone fracture.
      Comparison analysis of genders showed that there was a significant difference in
      favor of men (P<.05). The lumbar BMD, neck T-, and Z-scores were significantly
      higher among patients treated with alendronate than historical controls (P<.05).
      After 3 months, serum PTH was increased and serum osteocalcin and urinary DPD
      were reduced. No severe side effects from alendronate treatment were observed
      during the study. CONCLUSION: A direct sign of the success of our study was no
      fracture observed during the first postoperative year. Alendronate should be
      considered for patients with low bone mass after liver transplantation.

PMID- 16797330
TI  - Bone mineral density in adults transplanted in childhood for liver disease.
AB  - INTRODUCTION: It remains unclear whether bone mineral density (BMD) is
      compromised in adult life after liver transplantation (LT) during childhood.
      METHODS: This was a cross-sectional study of total body (TB) and lumbar spine
      (LS) dual-energy X-ray absorptiometry, anthropometry, and data collected, which
      included a physical activity questionnaire. RESULTS: Fifteen patients were
      enrolled. Mean age at LT was 10.6 (4.5) years (range 1.6 to 18.4). The mean
      posttransplant period was 12.0 (4.1) years (range 4.4 to 16.7); six were men. The
      mean TB BMD, 1.11 (0.12) g/cm2, was similar to LS BMD, 1.15 (0.17) g/cm2 (P=.82).
      The Z-score mean was lower for TB BMD, -0.92 (1.2), and LS BMD, -0.41 (1.2)
      (P=.22). There was no effect from gender, pretransplant cholestasis (9/15 cases),
      age at LT, and time since LT. BMD (Z-score) was better for those on
      corticosteroids (9/15 cases): TB BMD -0.42 (1.20) versus -1.77 (0.86) (P=.04); LS
      BMD 0.14 (1.00) versus -1.54 (1.03) (P=.03). Anthropometry Z-scores were height 
      0.04 (0.70), weight -0.33 (0.39), and BMI -0.32 (0.37). There was no correlation
      between Z-scores for BMD and any of the anthropometry parameters. CONCLUSION:
      Although the mean TB BMD was lower in transplanted patients than would be
      expected for the general population, overall BMD and anthropometry were with the
      normal adult ranges for adults who had undergone LT in childhood.

PMID- 16797331
TI  - Vascular complications after pediatric liver transplantation from the living
      donors.
AB  - Early arterial or portal vein thrombosis is a complications that can lead to
      graft loss and patient death or need of immediate retransplantation. The aim of
      the study was to assess the incidence, causes, treatment, and outcome of vascular
      thrombosis after living related donor liver transplantation (LRdLTx). Between
      1999 and 2004 71 LRdLTx were performed in children aged from 6 months to 10
      years. Vascular thrombosis was found in 12 recipients. Hepatic artery thrombosis
      (HAT) occurred in 4 (5.6%), portal vein thrombosis (PVT) in 8 (11.2%) cases. HAT
      occurred 5 to 8 days, PVT 1 to 22 days after LTx. Diagnosis of vascular
      thrombosis was confirmed by routine Doppler ultrasound examination. Thrombectomy
      was successful in one patient with HAT and in three patients with PVT. Venous
      conduit was performed in one patient with PVT after second thrombosis. Two
      children developed biliary strictures as a late complication of HAT and required
      additional surgical interventions. Two children with PVT developed portal
      hypertension with esophageal bleeding, which required surgical intervention; one
      another underwent endoscopic variceal ligation for grade III varices. Follow-up
      ranged from 7 to 60 months. One patient died as a result of HAT after
      retransplantation due to multiple intrahepatic abscesses 2 months after first
      transplant. Any risk factors of vascular thrombosis that can be controlled should
      be avoided after transplantation. Routine posttransplant Doppler examination
      should be performed at least twice a day within 7 to 14 posttransplant days.
      Immediate thrombectomy should be always carried out to avoid late complications
      and even mortality.

PMID- 16797333
TI  - Percutaneous intravascular stents for treatment of portal venous stenosis after
      liver transplantation: midterm results.
AB  - Portal vein stenosis after liver transplantation is a relatively uncommon
      vascular complication that may result in graft loss if not promptly treated. The
      purpose of this study was to evaluate the midterm result of the use of
      intravascular stents for portal vein stenosis after liver transplantation. From
      April 2004 to September 2005, percutaneous transhepatic balloon dilation with
      stent deployment was performed in nine cases. Varices were embolized with
      stainless steel coils in two cases. No procedure-related complication occurred.
      Portal venous patency was maintained in all nine patients from 6 to 19 months
      (mean 10 months). In conclusion, an intravascular stent is an effective treatment
      for the portal vein stenosis after liver transplantation with excellent midterm
      patency.

PMID- 16797332
TI  - Acute hepatic vein thrombosis after liver transplantation in a child with biliary
      atresia and absent inferior vena cava.
AB  - Stenosis of the hepatic venous outflow anastomosis is rare after liver
      transplantation. Hepatic venous outflow obstruction affects 5.1% to 7% of
      transplanted patients. Clinical findings among children include massive ascites
      and abdominal pain and laboratory findings demonstrate altered liver function
      tests and coagulopathy. In this article, we report a case of hepatic venous
      thrombosis occurring 22 days after living-related liver transplantation. The
      patient was treated with hepatic venoplasty and stent implantation.

PMID- 16797334
TI  - Extrahepatic metabolism and renal effects of sevoflurane in a case of liver
      transplantation.
AB  - In a case of liver transplantation, sevoflurane metabolism was studied to
      investigate if sevoflurane has an extrahepatic metabolism or possible
      nephrotoxicity in the presence of chronic liver disease. Plasma blood urea
      nitrogen (BUN) and creatinine and urine levels of N-acetyl glycosaminidase (NAG)
      and beta2 microglobulin were assessed intraoperatively and for 11 days
      postoperatively. We observed a close relation between urine NAG excretion and
      urine inorganic fluoride levels in the intraoperative period and early
      postoperative days. The NAG levels were greater than normal despite the peak
      serum inorganic fluoride concentration of 18.94 micromol/L. No impairment was
      observed in serum BUN or creatinine levels in these periods.

PMID- 16797335
TI  - De novo autoimmune hepatitis following liver transplantation for primary biliary
      cirrhosis.
AB  - De novo autoimmune hepatitis (AIH) is a rare disorder first described in 1998. It
      appears in patients with liver transplants for non-AIH etiology. The few cases in
      the literature make it a little known entity due to mechanisms that are unclear.
      We present the case of a woman with a liver transplant whose graft developed de
      novo AIH. Diagnosed with primary biliary cirrhosis, the patient underwent liver
      transplantation for refractory pruritus. Sixteen months after transplantation, we
      detected alterations in the hepatic profile with hypertransaminasemia and
      elevated alkaline phosphatase, together with elevated antinuclear antibodies. IgG
      levels were normal. Histological findings indicated AIH. The patient responded
      rapidly to treatment with prednisolone and azathioprine. De novo AIH in patients
      transplanted for PBC may cause graft dysfunction. This report also analyzes the
      case with respect to the other four reported cases, discussing etiologic
      hypotheses.

PMID- 16797336
TI  - Bilateral drop-foot after orthotopic liver transplant.
AB  - Patients may demonstrate various neuromuscular abnormalities after liver
      transplantation. We report a patient who developed bilateral drop foot after
      orthotopic liver transplantation. He was diagnosed with critical illness
      polyneuropathy. During follow-up, his complaints gradually recovered and his
      electrodiagnostic findings improved.

PMID- 16797337
TI  - Renal impairment after living donor liver transplantation.
AB  - BACKGROUND: There are few reports of postoperative renal impairment after living
      donor liver transplantation (LDLT). METHODS: We reviewed 246 LDLT recipients to
      examine the effects of postoperative renal impairment on the results of LDLT.
      RESULTS: The incidence of renal impairment and the requirements for postoperative
      renal replacement therapy were 29% and 9%, respectively. Intraoperative blood
      loss (P<.0001) and preoperative serum creatinine (P=.0002) were significant
      independent risk factors for the development of early renal dysfunction. Patients
      who required renal replacement therapy had a lower survival rate (P=.01).
      CONCLUSIONS: We identified the risk factors for postoperative renal impairment,
      providing useful metrics to establish a treatment strategy for high risk liver
      transplant patients.

PMID- 16797338
TI  - Posttransplant lymphoproliferative disorders in liver transplanted patients: a
      report of four cases.
AB  - BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) are an uncommon
      but important cause of morbidity and mortality in solid organ transplant
      recipients. They are often the result of Epstein-Barr virus (EBV)-induced
      proliferation of B-lymphocytes in the setting of immunosuppression. PATIENTS AND
      METHODS: We retrospectively analyzed four cases of PTLD after liver
      transplantation. In all patients immunosuppression was reduced and anti-CD20
      monoclonal antibody (rituximab) was administered. In two of four patients, EBV
      viral load was positive in the peripheral blood, and gancyclovir was therefore
      also prescribed. Chemotherapy (CHOP) was used as a rescue in the event of
      treatment failure. RESULTS: Even if no severe adverse events were observed during
      the treatment period, our treatment approach to PTLD was not effective, and only
      one patient out of four is still alive. CONCLUSIONS: Well-designed clinical
      trials are necessary to evaluate the role of this combined approach in the
      treatment of PTLD in liver transplant recipients.

PMID- 16797339
TI  - Ten-year experience with living related donated splenic transplantation for the
      treatment of hemophilia A.
AB  - AIM: Six cases of hemophilia A treated with living related donated splenic
      transplantation (LRDST) were performed over 10 years. METHODS: We reviewed the
      six consecutive cases of LRDST from 1992 to 2002. Three patients received whole
      spleen allografts and the other three, partial spleen allografts. All allografts
      were transplanted to the extraperitoneal space in the right iliac fossa by an end
      to-end anastomosis between the splenic artery and the internal iliac artery and
      an end-to-side anastomosis between the splenic vein and the external (or common)
      iliac vein. After the operation, a combined regimen with cyclosporine,
      azathioprine, anti-lymphocyte globulin, OKT3, was administered to suppress the
      immune reaction. RESULTS: The functional period of the allografts varied between
      30 days to 4 years. Patient factor-VIII (F-VIII) levels rose from less than 5%
      before operation to 15% to 56% postoperatively. One patient died from central
      nervous system complications. Another lost his graft because exogenous F-VIII was
      not supplemented in timely fashion at the onset of rejection. And the third could
      no longer afford the expensive immunosuppressive drugs at 2 years after the
      operation and eventually lost the spleen. The remaining three patients presently
      have regained self-support, among whom one has survived for 4 years. CONCLUSION:
      Though the sample pool is relatively small, our clinical observations tend to
      confirm LRDST as a feasible, effective treatment for hemophilia A.

PMID- 16797340
TI  - Impact of optimal heart failure medical therapy on heart transplant listing.
AB  - The data assessing the prognostic value of peak exercise oxygen consumption (VO2)
      in heart failure (HF) patients is largely derived from cross-sectional studies in
      which medical therapy was not maximized in all eligible patients and no clear
      explanation was given as to why such was the case. To assess the relative
      prognostic value of peak VO2 with respect to baseline medical therapy and its
      potential impact on transplant listing, 1-year event-free (death or left
      ventricular assist device placement) survival was compared among 341 HF patients,
      stratified in three groups based on peak VO2 (<10, 10 to 14, and >14 mL/min/kg).
      Similar analysis was performed on a subset of 288 patients who were on optimal
      medical therapy within this group. Average age of the study population was 55+/
      11 years, ejection fraction was 23%+/-08%, and peak VO2 was 12.4+/-3.6 mL/min/kg.
      One-year event-free survival for the overall cohort was: peak VO2<10 (n=87),
      63.2%; 10 to 14 (n=141), 81.1%; and >14 mL/min/kg (n=113), 90.2%. Patients with
      the same groups who were on optimal therapy had an event-free 1-year survival as
      follows: <10 (n=69), 72.4%; VO2 10 to 14 (n=127), 91.5%; and >14 mL/min/kg
      (n=92), 94.6%. In conclusion, cross-sectional assessment of HF prognosis may be
      misleading. In the intermediate risk group, this can significantly impact on
      medical decisions (eg, transplant listing). Optimization of therapy and long-term
      follow-up by a specialist may impact transplant listing.

PMID- 16797341
TI  - Effect of age on outcomes after left ventricular assist device placement.
AB  - The influence of age on outcomes after left ventricular assist device (LVAD)
      implantation is not well studied. To address this question, we assessed 222
      patients who underwent LVAD placement and were divided into quartiles based on
      age (years): group 1, <or=44; group 2, 45 to 53; group 3, 54 to 59; and group 4,
      >or=60. Eighty-four patients died on LVAD support. Six- and 12-month survivals
      for the four groups of LVAD patients were 67.7, 73.7, 49.8, and 38.2, and 49.4,
      57.3, 42.7, and 26.2, respectively (all P<.01). Older patients showed a higher
      risk of infections, embolic strokes, and respiratory complications. They were the
      least likely to undergo reoperations postimplantation (56%, 53%, 50%, 46%,
      P=.06). After adjusting for baseline differences between the groups, there was a
      trend toward increasing mortality with age, which did not reach significance
      (odds ratio 1.93; 95% confidence interval 0.95 to 3.92 for the oldest quartile as
      compared with the youngest). In conclusion, these results suggest in the absence
      of other high risk factors, age alone should not be used as an independent
      contraindication for LVAD implantation.

PMID- 16797342
TI  - Anemia in heart failure may warrant more aggressive listing for cardiac
      transplantation.
AB  - Peak exercise oxygen consumption (VO2, in mL/min/kg) is a reliable prognostic
      marker in heart failure (HF). Anemia, which is common in HF, affects both
      exercise capacity and prognosis. In this study, we assessed the relationship
      between peak VO2 and prognosis among HF patients with and without anemia. Data on
      344 HF patients were divided into three groups based on peak VO2 (<10, 10 to 14,
      and >14). Each group stratified by the presence of anemia (<13 mg/dL in men and
      <12 mg/dL in women) was compared for death or left ventricular assist device
      (LVAD) placement, and death or LVAD or transplantation. The mean patient age was
      53.4+/-11.8 years; hemoglobin level, 12.8+/-1.8 mg/dL; and average follow-up,
      629+/-459 days. Overall 32% of patients were anemic. The presence of anemia
      significantly impacted outcomes among patients with peak VO2<10, namely 42.2%
      versus 18.9% death or LVAD need (P=.01) and 66.7% versus 43.3% death or LVAD or
      transplantation (P=.06) for anemic versus nonanemic patients, respectively. The
      prognosis was similar among groups with higher peak VO2. After adjusting for
      baseline differences, anemic patients with peak VO2<10 were at higher risk for
      adverse outcomes: odds ratio (OR) 3.69 (95% confidence interval [95% CI] 1.31 to
      9.87) for death or LVAD; and OR 5.67 (95% CI=1.42 to 19.4) for death or LVAD or
      transplant. Anemia significantly impacted the prognosis of HF patients with peak
      VO2 less than 10 mL/min/kg. Since these patients are most likely to be evaluated
      for transplantation, the presence of anemia may further help to stratify
      prognosis in this group.

PMID- 16797343
TI  - Improved survival with statins, angiotensin receptor blockers, and steroid
      weaning after heart transplantation.
AB  - Various immunosuppressive and adjunctive pharmacological regimens exist for
      cardiac transplantation, though the associations between these regimens and long
      term survival are unclear. We reviewed demographic, clinical, and pharmacological
      data from 220 consecutive adult heart transplant recipients between 1986 and 2003
      who survived beyond 3 months. Immunosuppression was cyclosporine-based (n=94) or
      tacrolimus-based (n=126), and 104 patients were weaned off steroids (all
      receiving tacrolimus). Covariates of mortality were assessed in a Cox
      proportional hazards analysis. The mean age was 5.2+/-13 years. Survival was 96%,
      88%, and 81% at 1, 3, and 5 years, respectively. Significant covariates
      associated with mortality included pretransplant diabetes mellitus (hazard ratio
      [HR] 2.83, 95% confidence interval [CI] 1.45 to 5.04), black race (HR 1.41, 95%
      CI 1.01 to 1.94), higher pretransplant creatinine clearance (HR 0.99, 95% CI 0.98
      to 1.00), steroid withdrawal (HR 0.60, 95% CI 0.39 to 0.85), and exposure to a
      statin (HR 0.53, 95% CI 0.40 to 0.70) or an angiotensin receptor blocker (HR
      0.50, 95% CI 0.20 to 0.95) after transplantation. Treatment with a statin, an
      angiotensin receptor blocker, and steroid withdrawal were each associated with
      improved survival in heart transplant recipients. These findings warrant
      prospective study, with specific emphasis on identifying the clinical effects of
      these medications in transplant recipients.

PMID- 16797345
TI  - Unusual case of an 18-year-old heart transplant recipient with endocardial
      fibroelastosis.
AB  - An 18-year-old female Japanese patient who suffered from heart failure and severe
      pulmonary hypertension was referred to our clinic. The etiology of her
      cardiomyopathy was unclear. Inhaled prostacyclin therapy resulted in an
      improvement of pulmonary arterial pressure and allowed us to avoid lung
      transplantation. Heart transplantation resulted in a complete remission of her
      respiratory function. Autopsies of the explanted heart revealed massive
      endomyocardial fibroelastosis. We concluded that endomyocardial fibroelastosis
      has to be considered a cause of heart failure in young adults with unclear
      cardiomyopathy.

PMID- 16797344
TI  - Long-term safety and effectiveness of statins for heart transplant recipients in
      routine clinical practice.
AB  - BACKGROUND: Whereas the efficacy of statins after heart transplantation (HT) in
      controlled study settings has been clearly demonstrated, more extensive data are
      required on the safety and effectiveness of long-term treatment in routine
      clinical practice. METHODS: We analyzed the risks and benefits in clinical
      practice of treatment with statins in all patients who survived HT for at least a
      month from December 1985 through 2001. RESULTS: During a mean follow-up of 4.8+/
      3.8 years, 186 patients were treated with statins (for a median duration [25th to
      75th percentile] of 29 [12 to 54] months), while 48 received dietary therapy
      alone. Patients treated with statins (pravastatin, 48%; atorvastatin, 37%;
      simvastatin, 14%) presented linearized rates of rhabdomyolisis, myositis, and
      significant transaminase elevation of 0.37%, 0.74%, and 0.37% per year of
      treatment, respectively (no fatal event occurred). Low-density lipoprotein
      decreased after statins by 19% (P<.001). At multivariate analysis, treatment with
      statins was independently associated with reduced risk of cardiac allograft
      vasculopathy and overall mortality (P<.001). CONCLUSIONS: Our data provide
      necessary confirmation of the safety and effectiveness in routine clinical
      practice of appropriately monitored long-term administration of statins
      (particularly atorvastatin, pravastatin, and simvastatin) in the chronic post-HT
      phase. Strict follow-up is needed for HT recipients receiving high doses of
      statins with/without other medications potentially exacerbating the risk of
      adverse effects.

PMID- 16797346
TI  - Successful heterotopic heart transplant after cardiopulmonary bypass rescue of an
      arrested donor heart.
AB  - Global heart transplantation has declined due to the donor shortage. The use of
      marginal donors has therefore been reintroduced. According to the history of
      heart transplantation, heterotopic heart transplant has played an important role
      in the precyclosporine era. In those circumstances, native heart and donor heart
      worked together to support each other against rejection or progressive heart
      failure. However, heterotopic transplantation has complicated surgical techniques
      and requirements for postoperative surveillance. Most training fellows have
      limited experience with this approach. At present more than 1000 cardiac surgical
      centers perform heart transplantation, but only 50 centers have experience in
      performing-heterotopic procedures. Using mechanical circulatory support for the
      posttransplant period is well developed in most centers. However, using
      mechanical circulatory support for heart donor with the intention of rescuing the
      heart has not been reported. Herein, we report a successful heterotopic heart
      transplantation after rescue with cardiopulmonary bypass of an arrested donor
      heart.

PMID- 16797347
TI  - Is third-time heart retransplantation justifiable?
AB  - Since repeat heart transplantation traditionally carries higher risk than primary
      engraftment, we tested the hypothesis that third-time cardiac allograft
      transplantation is associated with prohibitive mortality and morbidity. The
      cohort of all third-time cardiac retransplants performed at our institution (n=3)
      and reported to UNOS from 1987 to 2002 (n=10) was reviewed. The primary endpoints
      were early and late mortality. Extending the study frame through 2003 captures a
      total of 5 and 15 third-time heart transplant recipients in UCLA and UNOS
      databases, respectively. Of the 15 patients undergoing third-time retransplants,
      preoperatively one was ventricular assist device-dependent, four were on
      intravenous inotropes, and two had creatinine levels greater than 2.5.
      Additionally, four were male recipients of female donor hearts and the mean donor
      ischemic time was 2.6 hours. One patient was diagnosed with acute allograft
      rejection, 13 with coronary artery vasculopathy/chronic rejection, and one with
      primary graft failure. At our institution, five patients underwent a third heart
      transplant. There was no early or hospital mortality. One patient died late from
      transplant coronary artery disease and another following a fourth allograft. The
      mortality rate for third-time heart allograft recipients is acceptable. These
      results are influenced by small sample size, younger age, case selection, and
      operations at select, high-volume institutions with significant experience.

PMID- 16797348
TI  - Late humoral rejection in a cardiac transplant recipient treated with the anti
      CD20 monoclonal antibody rituximab.
AB  - Humoral or vascular rejection results from a B cell-mediated production of
      immunoglobulin (Ig) G antibody against a transplanted organ, producing immune
      complex deposition on the vascular endothelium, activation of the complement
      cascade, generation of endothelial dysfunction, and regional ischemic injury.
      Antibody-mediated rejection, which may be accompanied by hemodynamic compromise,
      is associated with reduced long-term graft survival. Patients believed to be at
      an increased risk of developing humoral rejection include women, particularly
      those with high levels of panel reactive antibodies, cytomegalovirus
      seropositivity, and positive cross matches, and subjects with prior sensitization
      to OKT3. Treatment options for humoral rejection include plasmapheresis to lower
      the circulating immunoglobulin levels followed by high-dose cyclophosphamide to
      reduce the B-cell population. Other modalities include total lymphoid
      irradiation, photophoresis, splenectomy, and, for treatment failures,
      retransplantation. Rituximab is a chimeric humanized monoclonal antibody directed
      against the pan B-cell surface molecule, CD20. It is approved for the treatment
      of low-grade B-cell non-Hodgkin's lymphoma. It has also been used successfully
      for the treatment of posttransplant B-cell lymphoproliferative disease. We report
      a case of late humoral rejection successfully treated with rituximab.

PMID- 16797349
TI  - Trapidil decreases the aggregation of platelets from heart transplant recipients
      ex vivo.
AB  - Heart transplant recipients show platelet hyperaggregability, which may be
      related to the incidence of graft vasculopathy. We investigated whether trapidil
      can inhibit the aggregation of platelets from these patients. Platelet count,
      mean platelet volume (MPV), and adenosine diphosphate (ADP)-induced platelet
      aggregation were determined in 18 heart transplant recipients and 12 healthy
      subjects. Additionally, platelet-rich plasma from the patients was incubated with
      trapidil or with saline, prior to measuring ADP-induced aggregation. The MPV was
      significantly greater in patients compared to controls (9.4+/-1.1 vs 8.5+/-0.7
      fL; P=.01), and ADP-induced platelet aggregation was significantly increased in
      patients compared to controls (81.2%+/-13.1% vs 69.6%+/-16.2%; P=.04,
      respectively). The trapidil-treated samples showed significantly decreased
      platelet aggregation compared to the control samples (24.2%+/-12.6% vs 66.7%+/
      11.7%; P<.001). Platelets from heart transplant recipients showed an increased
      MPV and increased ADP-induced aggregation. Trapidil effectively reduced the ADP
      induced aggregation ex vivo.

PMID- 16797350
TI  - Cutaneous infection with rapidly-growing mycobacterial infection following heart
      transplant: a case report and review of the literature.
AB  - Nontuberculous mycobacteria are ubiquitous and infrequently cause disease in
      humans, most commonly in immunocompromised hosts. One type of nontuberculous
      mycobacteria is Mycobacterium abscessus. This rapidly growing mycobacterium is a
      soil or water saprophyte. It was previously classified as a subspecies of
      Mycobacterium chelonae; however, current taxonomy now designates it as a separate
      species. Rapidly growing mycobacteria are resistant to the usual antituberculous
      drugs. This emphasizes the need for tissue diagnosis and obtaining specimens for
      culture and drug susceptibility testing. M abscessus has been reported to cause
      infection in renal transplant patients, but is less well described in cardiac
      transplant recipients. We report the case of a 65-year-old man who presented 5
      years after transplantation for heart failure, with a 2-day history of
      progressive right lower extremity swelling and redness. He recalled no antecedent
      trauma and denied any unusual epidemiologic exposure. Medical history included
      diabetes with peripheral neuropathy and renal insufficiency, hypertension, and
      right-sided heart failure felt to be due to obstructive sleep apnea. A punch
      biopsy of the area grew M abscessus sensitive only to clarithromycin (MIC not
      reported), amikacin (30 microg/mL), and kanamycin (30 microg/mL). On subsequent
      clinic visits, the patient had decreased leg swelling and resolution of the
      papular lesions. Ten weeks into antimycobacterial therapy, the patient had an
      increase in creatinine to 4.9 mg/dL from a baseline of 2.0 with fluid overload
      necessitating discontinuation of aminoglycoside therapy. He completed 6 months of
      treatment with oral clarithromycin. We describe these findings and review the
      literature in this report.

PMID- 16797351
TI  - Pulmonary complications in heart transplant recipients.
AB  - BACKGROUND: Heart transplantation is an important therapeutic option for patients
      with end-stage disease, but is associated with major pulmonary complications.
      PATIENTS AND METHODS: We retrospectively reviewed the posttransplant follow-up of
      34 orthotopic heart transplant recipients. RESULTS: Two of the 34 patients died
      of cardiac failure in the early postoperative period. Among the surviving
      patients, 10 (31.3%) developed pulmonary complications, all within the first 6
      months: hospital-acquired bacterial pneumonia in five, fungal pneumonia in three,
      posttransplant lymphoproliferative disease in one, and community-acquired
      pneumonia in one patient. None of the patients developed transplantation-related
      malignancy. The overall mortality was 35.3%. Pneumonia-related mortality rate of
      14.7% was due to early-onset nosocomial pneumonias, which were caused by
      bacterial and opportunistic microorganisms. Extrapulmonary causes of mortality
      were cardiac failure, meningitis, septicemia, and acute rejection.
      Cytomegalovirus antigenemia in the first month was associated with a poor
      prognosis. The frequency of pulmonary complications was higher among older
      patients and those who developed moderate rejection in the first month (P=.014
      and P=.036, respectively). CONCLUSION: Pulmonary infections after heart
      transplantation occurred more frequently during the first 6 months
      posttransplantation, accounting for a significant portion of the
      posttransplantation mortality.

PMID- 16797352
TI  - Case report: a left donor lung implanted in the recipient's right thorax for the
      therapy of pulmonary fibrosis.
AB  - A 68-year patient suffering from pulmonary fibrosis underwent single lung
      transplantation on April 4, 2005. Because the ipsilateral donor lung was severely
      damaged, we had to implant the contralateral lung--the left lung--to the right
      thorax, and finally this patient recovered.

PMID- 16797353
TI  - Hybrid pulmonary artery conduit angioplasty for heterotopic heart
      transplantation.
AB  - Heterotopic heart transplantation is rare in clinical practices. It carries
      technical difficulty not only during transplantation procedures, but also in the
      postoperative surveillance. We report two cases of heterotopic heart
      transplantation, which were complicated by pulmonary artery conduit stenosis
      within 2 years. We applied a less invasive approach combining cardiovascular
      surgeons with an interventional cardiologist. Through the donor heart right
      ventricular outflow tract, we performed balloon angioplasty and stent deployment.
      An excellent angiographic result with minimal residual pressure gradient was
      achieved in both patients.

PMID- 16797354
TI  - Outcome and morbidity of pancreas transplantation in a single Spanish
      institution.
AB  - BACKGROUND: Pancreas transplantation is nowadays the only treatment to
      reestablish normal blood glucose in diabetic patients. Moreover, transplantation
      may also prevent and possibly even revert diabetes-related complications. We
      present our results with the first 4 years of a pancreas transplantation program.
      MATERIALS AND METHODS: From February 2000 to June 2004, we performed 43 pancreas
      transplants in 42 recipients. In all cases the technique was enteric drainage of
      the exocrine secretions and systemic venous derivation to the inferior vena cava
      for endocrine secretions. RESULTS: A simultaneous pancreas-kidney transplant was
      performed in 37 (88.1%) patients, a pancreas after kidney in 4 (9.5%) patients,
      and a retransplant in 1 (2.4%) patient. Glycosylated hemoglobin and C peptide
      returned to normal values in all cases. Patient and graft survivals were 91% and
      84%, respectively, after a median follow-up of 19 months. The rate of
      reoperations was 31% with an overall 16% graft loss. CONCLUSIONS: Our results
      were comparable to those of larger series.

PMID- 16797355
TI  - Platelet counts are persistently increased following simultaneous pancreas and
      kidney transplantation.
AB  - BACKGROUND: Increased platelet counts has been reported to be a sequela of
      pancreas transplantation and even incriminated in the increased rate of
      thrombosis of pancreas grafts. The aim of the study was to measure the platelet
      counts after simultaneous kidney-pancreas transplantations compared to kidney
      transplants alone in diabetic patients. METHODS: This retrospective case-control
      study included 57 patients who received simultaneous pancreas and kidney
      transplants (SPK), from 1985 to 2000 and had functioning grafts for more than 1
      month. The control patients were 38 type I diabetic recipients of kidney
      transplants alone (KTA), matched for sex, era, and immunosuppression. The
      platelet counts, white cell counts, and hemoglobin were analyzed on the
      preoperative day, weeks 1 to 6, 3 months, 6 months and 1 year. RESULTS: The mean
      age of the SPK group was significantly lower than that of the KTA group (39.8+/
      8.3 versus 48.2+/-11.7, P<.01). Significantly higher platelet counts were
      demonstrated during weeks 2 to 6, which persisted at 3 months and at 1 year among
      the SPK compared to the KTA group. Although significantly higher white cell
      counts and lower hemoglobin levels were seen among the SPK versus KTA group
      during weeks 3 to 6, it did not persist after 3 months. CONCLUSION: The mean
      platelet counts of patients with simultaneous pancreas and kidney transplantation
      was significantly higher than that of diabetic patients with kidney transplants
      alone. This thrombocytosis persisted up to the first year and cannot be explained
      by an increased amount of blood loss or higher infectious complications in the
      SPK group. Routine antiplatelet prophylaxis is recommended in this group of
      patients.

PMID- 16797356
TI  - Small intestinal submucosa improves islet survival and function in vitro culture.
AB  - INTRODUCTION: Most centers maintain isolated human islet preparations in tissue
      culture to improve the safety as well as the practicality of islet
      transplantation. However, maintaining viability and recovery of islets remains a
      challenge. Extracellular matrix (ECM) is one of the most important components of
      the islet microenvironment. Reconstruction of the cell-matrix relationship seems
      to be necessary to sustain the structure and function of differentiated islets.
      Small intestinal submucosa (SIS), a natural ECM, is well known to promote wound
      healing, tissue remodeling, and cell growth. The purpose of this study was to
      evaluate recovery and function of isolated rat pancreatic islets during in vitro
      culture with SIS. METHODS: Pancreatic islets isolated from Wistar rats following
      intraductal collagenase distension, mechanical dissociation, and EuroFicoll
      purification were cultured in plates coated with multilayer SIS (SIS-treated
      group) or without (standard cultured group) for 7 or 14 days in an islet culture
      media of RPMI 1640 (Gibco). The islets from both experimental groups were stained
      and counted with dithizone. Islet recovery following culture was determined by
      the ratio of counts after culture to the yield of islets immediately following
      islet isolation. The viability of the islets was assessed by a glucose challenge
      test with low glucose (2.7 mmol/L), high glucose (16.7 mmol/L), and high glucose
      solution supplemented with 50 micromol/L 3-isobutyl-1-methylxanthine solution.
      The apoptosis of islet cells was measured by relative quantification of histone
      complexed DNA fragments by using enzyme-linked immunosorbent assay. RESULTS:
      After 7 or 14 days of in vitro tissue culture, the recovery in SIS-treated islets
      group was about double of that cultured in the plates without SIS coating. In the
      SIS-treated group, there was no significant difference between the short- and the
      long-term periods of culture (95.8%+/-1.0% vs 90.8%+/-1.5%, P>.05). Following
      incubation with high glucose (16.7 mmol/L) solution, the insulin secretion in the
      SIS-treated group showed a greater increase than the control group after 14 days
      of culture (20.7+/-1.1 mU/L vs 11.8+/-1.1 mU/L, P<.05). When islets were placed
      in the high glucose solution containing IBMX, the stimulated insulin secretion
      was more increased in the SIS-treated than in the control group despite the
      duration of the culture. The calculated stimulation index of SIS-treated group
      was about two to three times greater than the control group. In addition, the
      stimulation index of the SIS-treated group remained constant regardless of short
      term versus long-term culture (9.5+/-0.2 vs 10.2+/-1.2, P>.05). Much less
      apoptosis of islet cells occurred in the SIS-treated than in the control group.
      CONCLUSION: Coculture of isolated rat islets with native sheetlike small
      intestinal submucosa seemed to build an ECM for islets providing possible
      biotrophic and growth factors that promote the recovery and subsequent function
      of islets.

PMID- 16797358
TI  - Early changes of small intestine function in rats after liver transplantation.
AB  - OBJECTIVE: The aims of this study were to explore the concomitant changes of the
      barrier function, bacterial translocation, absorption, and small intestinal
      motility in rats after liver transplantation and to correlate these changes with
      levels of plasma endotoxin. METHODS: Thirty Wistar rats were divided randomly
      between a sham operation group (n=10) and a liver transplantation group (n=10
      pairs). The intestinal transit function, intestinal permeability, bacterial
      translocation, absorption function, levels of plasma endotoxin, and nitrogen
      monoxide (NO) changes in plasma and small intestinal mucosa were monitored in the
      two groups. The expression of iNOS mRNA in the intestine was investigated by
      reverse transcriptase-polymerase chain reactions. RESULTS: Significant
      differences were observed between the liver transplantation group and the sham
      operation group for aspects of intestinal transit function, intestinal
      permeability, bacterial translocation, absorption function, and NO changes in
      both plasma and small intestine. Compared with the sham operation group, the
      expression of iNOS mRNA was significantly increased (P<.05) in the small
      intestine of rats that had undergone liver transplantation. CONCLUSION: The
      functions of motility, barrier, and absorption in the intestine were decreased
      among rats that had undergone liver transplantation. Reduced motility in the
      small intestine of the rats following liver transplantation may be related to the
      enhanced expression of iNOS in the intestine with a negative correlation to
      plasma levels of endotoxin.

PMID- 16797357
TI  - Prolongation of rat intestinal allograft survival by administration of donor
      interleukin-12 p35-silenced bone marrow-derived dendritic cells.
AB  - Severe graft rejection remains an important obstacle in intestinal
      transplantation. In this study, we demonstrated that intravenous injection of
      interleukin (IL)-12 p35 siRNA-transfected dendritic cells (DCs) into recipient
      rats prolonged the survival of intestinal allografts. Serum IL-2 and interferon
      gamma levels in the IL-12 p35 siRNA-transfected DCs treatment group were both
      significantly lower than in control groups at 7 days after transplantation.
      Further study is required to investigate the operative pathways and to optimize
      the strategy targeting dendritic cells to induce tolerance to intestinal
      allografts.

PMID- 16797359
TI  - Organ changes and bacterial translocation in a rat model of chronic rejection
      after small bowel transplantation.
AB  - Rejection after small bowel transplantation (SBTx) may allow bacterial
      translocation damaging the liver and lungs. This study investigated these issues
      in a rat model of chronic rejection. MATERIALS AND METHODS: Orthotopic SBTx was
      performed in syngeneic (SYN) (ACI-ACI, n=8) and allogeneic (ALLO) (ACI-Lewis,
      n=8) rat strain combinations. Cyclosporine was given to ALLO rats for 28 days.
      Animals were sacrified between 55 and 65 days. Lymph nodes and venous samples
      were cultured; Escherichia coli DNA was assessed by polymerase chain reaction. We
      measured intestine, liver, spleen, and lung protein and DNA contents. Chronic
      rejection was histologically confirmed. RESULTS: Two of eight and four of eight
      rats died in the first week after SYN and ALLO SBTx, respectively. There were no
      differences in organ weights or DNA and protein contents compared with the
      controls. Gram-negative enteric bacteria were found in two of four ALLO and two
      of six SYN rats (ns), and aerobic gram-positive were found in two of four and two
      of six (ns), respectively. Anaerobic growth occurred in mesenteric lymph nodes in
      only one ALLO rat. E. coli DNA was negative in all animals. Lungs were severely
      emphysematous in ALLO rats with no histologic changes observed in the other
      phagocytic organs. Mild rejection was found in the intestine of ALLO rats.
      CONCLUSIONS: Bowel lesions in ALLO rats might be consistent with chronic
      rejection and lung lesions could be related to bacterial translocation after
      SBTx. However, contrary to our expectations, no significant bacterial
      translocation was demonstrated in either group at the end of the experiments.

PMID- 16797360
TI  - Taurine protects against ischemia-reperfusion injury in rabbit livers.
AB  - Ischemia-reperfusion injury is of major clinical relevance during liver
      transplantation. In the present study, the therapeutic efficacy of taurine to
      protect against ischemia-reperfusion injury was investigated in rabbit livers. We
      demonstrated that intravenous injection of taurine attenuated liver dysfunction
      as evidenced by reductions in serum alanine aminotransferase, aspartate
      transaminase, and alkaline phosphatase. The recovery of morphological and
      ultrastructural changes in the liver was also promoted by taurine. The mechanism
      of the protective effect of taurine seems at least to rely on antioxidation,
      since the lipoperoxides contents in liver tissues were significantly reduced
      among taurine-treated rabbits. These results suggest that taurine is a potent
      useful reagent to protect the rabbit liver from ischemia-reperfusion injury.

PMID- 16797362
TI  - Role of NF-kappaB as effector of IPC in donor livers before liver transplantation
      in rats.
AB  - The objective of this study was to investigate the effect of ischemic
      preconditioning (IPC) on NF-kappaB activity during reperfusion early after liver
      transplantation in rats. METHODS: Male Sprague-Dawley (SD) rats were used as
      donors and recipients of orthotopic liver transplantations. The donor liver was
      stored 2 hours in Ringer's solution at 4 degrees C preimplantation. IPC was
      performed by clamping of the portal vein and hepatic artery of the donor for 10
      minutes followed by reperfusion for 10 minutes before harvesting. At 1, 2, 4, and
      6 hours after portal vein reperfusion, graft samples were obtained to determine
      hepatic levels of NF-kappaB activity, tumor necrosis factor (TNF)-alpha and
      intercellular adhesion molecule (ICAM)-1. Blood samples were obtained to measure
      serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). RESULTS:
      After liver transplantation without IPC, serum levels of ALT and LDH increased
      significantly compared with the sham-operated group. Among the IPC group, serum
      ALT and LDH decreased significantly. NF-kappaB activity in the graft increased
      within 6 hours after transplantation. Among the IPC group, NF-kappaB activity was
      significantly attenuated. Hepatic levels of TNF-alpha and ICAM-1 were
      significantly elevated in the non-IP group but both were reduced in the IPC
      group. CONCLUSION: IPC downregulated TNF-alpha and ICAM-1 expression in the
      graft, most likely through decreased NF-kappaB activation, and attenuated
      neutrophil infiltration after reperfusion.

PMID- 16797361
TI  - The enhancement of cellular cAMP with olprinone protects autotransplanted rat
      kidney against cold ischemia-reperfusion injury.
AB  - The administration of a cyclic nucleotide analog improves cold
      ischemia/reperfusion injury in several organs. The type 3 phosphodiesterase
      inhibitor olprinone is a potent stimulus that enhances cellular cAMP levels. The
      present study was performed to investigate the protective effects of enhanced
      intracellular cAMP levels by olprinone in rat orthotopic kidney transplantation.
      Autotransplantation and immediate contralateral nephrectomy were performed in
      Lewis rats after 18 hours of graft storage at 4 degrees C in University of
      Wisconsin (UW) solution with or without 25 microg/mL olprinone hydrochloride. At
      2 hours after reperfusion, serum and urinary biochemical indicators of renal
      dysfunction and injury were measured: serum creatinine, fractional excretion of
      Na+ and urinary N-acetyl-D-glucosaminidase. Additionally, intracellular cAMP in
      kidney tissues was measured by a radioimmunology method. Compared to the only UW
      solution group, olprinone hydrochloride significantly reduced the increased in
      serum creatinine, FENa and NAG caused by renal ischemia/reperfusion injury, after
      2 hours of reperfusion. The content of cAMP at the endpoint of 18 hours cold
      preservation was significantly greater in the UW plus olprinone hydrochloride
      group than that in the UW group. Two hours after reperfusion, the content of cAMP
      in the UW plus olprinone hydrochloride group was still significantly higher than
      that in the UW group without containing olprinone hydrochloride. These results
      support a beneficial effect of olprinone against cold ischemia and reperfusion
      injury via an increased intracellular cAMP levels.

PMID- 16797363
TI  - Evaluation of microperfusion disturbances in the transplanted liver after Kupffer
      cell destruction using GdCl3: an experimental porcine study.
AB  - BACKGROUND: Organ function after liver transplantation is determined by ischemia
      reperfusion injury. Destruction of Kupffer cells with gadolinium chloride (GdCl3)
      has been shown to have a possible preventive effect on the extent of this injury,
      which can be extrapolated by analyzing the distribution of hepatic
      microperfusion. The aim of this study was to evaluate the protective effect of
      GdCl3 on disturbances of microperfusion in the transplanted liver. METHODS:
      Landrace pigs were randomly divided into three groups. In the control group (CG;
      n=6) a mapping of the native liver was conducted. For mapping, the four hepatic
      liver lobes were named from right to left with A to D and every lobe was divided
      into three vertical segments (cranial, medial, and caudal). In each of these 12
      areas, microperfusion was quantified using a thermodiffusion probe (TD [mL/100
      g/min]). The other two groups were considered as transplanted treated group (TTG;
      n=10) and transplanted nontreated group (TnTG; n=10). The TTG received an
      infusion of 20 mg/kg GdCl3 intravenously 24 hours before organ harvesting. Then
      standardized orthotopic liver transplantation was performed. In TnTG,
      standardized orthotopic liver transplantation was carried out without prior GdCl3
      injection. In the recipients, the microperfusion of transplanted livers were
      mapped in both TnTG and TTG, in two different time points (1 hour [n=5] and 24
      hours (n=5]) after reperfusion. RESULTS: A significant reduction of macrophages
      in the TTG livers in comparison to the CG and TnTG livers was observed (P<.05).
      However, the number of macrophages in CG and TnTG livers showed no significant
      difference (P>.05). Regarding liver microperfusion, in TnTG, a marked
      heterogeneity was detected in the livers after reperfusion. Significant
      differences between liver lobes (horizontal planes; P=.032) and vertical layers
      of intralobar liver parenchyma (P=.029) were observed. The same pattern was seen
      in TTG livers after reperfusion and a significant difference between horizontal
      (P=.024) and vertical layers (P=.018) of liver tissue were observed. Comparing
      intralobar regional flow data between vertical planes 24 hours after reperfusion
      still showed a prominent variation of hepatic tissue perfusion in TnTG livers
      (P=.028). Within the same horizontal layers, no significant differences between
      lobes were measured anymore (P=.16). Contrary to TnTG, in TTG, a homogenous
      pattern of regional liver tissue perfusion was recorded 24 hours after
      reperfusion. Comparison of TD data on the liver regions showed no significant
      microperfusion differences in either horizontal (P=.888) or vertical (P=.841)
      layers. CONCLUSIONS: Application of GdCl3 resulted in a significant reduction of
      Kupffer cells. Twenty four hours after transplantation microperfusion showed a
      homogeneous pattern, which constituted an earlier and better recovery of the
      transplanted liver. Therefore, destruction of Kupffer cells reduced ischemia
      reperfusion injury and seemed to be responsible for the early recovery of
      microperfusion disturbances and thus for an improvement of graft function.

PMID- 16797364
TI  - Cell transplantation after the coculture of skeletal myoblasts and mesenchymal
      stem cells in the regeneration of the myocardium scar: an experimental study in
      rats.
AB  - In myocardial infarction and Chagas's disease, some physiopathological aspects
      are common: cardiomyocyte loss due to ischemia leads to a reduction of
      contractility and heart function. Different cells have been proposed for cellular
      cardiomioplasty. OBJECTIVE: Our goal was to evaluate the method of co-culture of
      skeletal muscle (SM) and mesenchymal stem cells (MSC) for cell therapy of heart
      failure in Chagas's disease (CD) and myocardium postinfarction (MI). METHODS: For
      MI, 39 rats completed the study at 1 month. Seventeen rats received cell therapy
      into the scar and 22 rats only medium. For CD, 15 rats completed the study at 1
      month including 7 that received cell therapy and eight followed the natural
      evolution. All animals underwent ecocardiographic analysis at baseline and 1
      month. Left ventricular, ejection fraction, end systolic, and end dyastolic
      volume were registered and analyzed by ANOVA. The co-culture method of SM and MSC
      was performed at 14 days (DMEM, with 15% FCS, 1% antibiotic, IGF-I,
      dexamethasone). Standard stain analysis was performed. RESULTS: For MI ejection
      fraction in the animals that received the co-cultured cells increased from
      23.52+/-8.67 to 31.45+/-8.87 (P=.006) versus the results in the control group:
      26.68+/-6.92 to 22.32+/-6.94 (P=.004). For CD, ejection fraction in animals that
      received the co-cultured cells increased from 31.10+/-5.78 to 53.37+/-5.84
      (P<.001) versus the control group values of 36.21+/-3.70 to 38.19+/-7.03
      (P=0.426). Histopathological analysis of the animals receiving co-cultured cells
      demonstrated the presence of myogenesis and angiogenesis. CONCLUSION: The results
      validated the product of SM and MSC co-cultures for treatment of diseases.

PMID- 16797365
TI  - Hematopoietic stem cell mobilization after rat partial orthotopic liver
      transplantation.
AB  - BACKGROUND: On the basis of the recently recognized potential of hematopoietic
      stem cells (HSC) to give rise to hepatocytes, we investigated the possibility
      that HSC could be mobilized and home to the injured liver promoting tissue repair
      after 50% partial orthotopic liver transplantation (PLTx) in the rat. METHODS:
      Using sex-mismatched (female to male) syngeneic SD rats, we performed 50% PLTx or
      whole orthotopic liver transplantation (WLTx) versus 50% partial hepatectomy
      (PHx) and sham operation (O). Elements with stem cell markers were detected in
      peripheral blood (PB) and in the liver. Liver injury and regeneration were
      estimated. The sex-determining region for Y chromosome gene (SRY) was used to
      define cell origin by in situ hybridization in liver sections. RESULTS:
      Comparison of WLTx and PHx groups showed a lower survival rate (50%), in the PLTx
      group were (P<.05). Further, the liver injury was more serious and the levels of
      serum biochemical parameters were higher. Compared with PHx groups, on days 3 and
      5 postoperatively, the mitosis index and the expression of PCNA were lower among
      the PLTx groups. Compared with WLTx and sham operation groups, beta2m-/Thy-1.1+,
      CD34+ cells in PB in PLTx groups and PHx were increased on day 1 postoperatively
      and decreased on the following days. Compared with PHx groups, beta2m-/Thy-1.1+,
      CD34+ cells were higher in PLTx. The CD34-, c-kit-, and Thy-1.1-positive cells
      detected in portal tract areas peaked during 3 to 5 days postoperatively in PLTx.
      Few SRY+ cells were detected in PLTx liver grafts. CONCLUSIONS: beta2m-/Thy-1.1+
      and CD34+ stem cells mobilized after PLTx and PHx may be related to the reduced
      size liver. Few HSC are involved in liver regeneration in PLTx.

PMID- 16797367
TI  - Stable maintenance of monkey embryonic stem cells in the absence of bFGF.
AB  - Monkey embryonic stem (ES) cells are useful tools in preclinical studies of gene
      therapy and tissue engineering as well as in primate developmental biology.
      However, their maintenance is not easy, requiring addition of bFGF to the medium.
      Herein, we have described a stable, cost-effective method that does not require
      bFGF. We used a high-density (1 to 1.5x10(5) cells/cm2) of mouse embryonic
      fibroblasts (MEF) as feeder cells to successfully maintain undifferentiated
      monkey ES cells for 2 years (approximately 150 passages). Furthermore, these ES
      cells were competent for electroporation of enhanced green fluorescent protein
      (EGFP) and subsequent drug selection procedures. We were able to establish EGFP
      expressing cell lines using this culture condition. These cell lines expressed
      undifferentiated markers, such as alkaline phosphatase, SSEA-4, TRA-60, and TRA
      81. In addition, strong EGFP expression was observed after differentiation into
      cardiomyocytes, neurons, or adipocytes, suggesting that these cell lines are a
      useful tool to study cell transplantation. This method simplifies the culture of
      monkey ES cells.

PMID- 16797366
TI  - Usefulness of sequential Aspergillus galactomannan antigen detection combined
      with early radiologic evaluation for diagnosis of invasive pulmonary
      aspergillosis in patients undergoing allogeneic stem cell transplantation.
AB  - BACKGROUND: Early diagnosis of invasive pulmonary aspergillosis (IPA) is
      important as prompt treatment with antifungal drugs may increase patient
      survival. Our study investigated the efficiency of routine testing of the
      Aspergillus galactomannan antigen (AGA) test in combination with chest CT scans
      for IPA diagnosis. PATIENTS AND METHODS: From February 2002 to June 2004, 74
      hemato-oncologic patients undergoing allogeneic stem cell transplantation were
      prospectively studied with serum AGA twice weekly from admission until death or
      discharge and weekly afterward when possible. Chest CT scans were performed when
      fever of unknown origin had lasted beyond 3 days of antibacterial therapy.
      RESULTS: Seven patients were classified with possible IPA and two patients,
      proven IPA. Fourteen patients showed positive results for AGA (OD index>or=1.0 on
      two subsequent sera). The sensitivity and specificity of the test were 100% and
      93%, respectively; the positive and negative predictive values were 64% and 100%,
      respectively. All patients with possible/proven IPA showed abnormal CT signs; in
      four cases, imaging signs followed AGA positivity (median 5 days), whereas in
      five cases they preceded serologic positivity (median, 8 days). In the nine
      patients with IPA, antifungal therapy was promptly instituted, including lipid
      formulations of amphotericin B (n=5) or caspofungin (n=4). In only two of the
      nine patients (22%) with IPA, the primary cause of death was fungal infection.
      CONCLUSIONS: The combination of AGA detection and early chest CT scans might be
      considered useful tools to detect minimal changes of IPA. Based on these
      findings, aggressive antifungal therapy should be initiated.

PMID- 16797368
TI  - Using gelatin scaffold with coated basic fibroblast growth factor as a transfer
      system for transplantation of human neural stem cells.
AB  - Gelatin scaffolds for ex vivo cell cultures are a promising development. These
      scaffolds can be used as three-dimensional skeletons for cell attachment and
      culture before transplantation. In this study, we isolated and cultivated neural
      stem cells from human brain tissues in serum-free medium (DMEM+F12 nutrient).
      Better neuron growth was observed using the tetrazolium assay (MTT) in the group
      when basic fibroblast growth factor (bFGF) was coated on the gelatin polymer
      scaffold. Further development of this nontoxic system may help the future
      development of transplantation of human neural stem cells.

PMID- 16797369
TI  - Effects of combined expression of human complement regulatory proteins and H
      transferase on the inhibition of complement-mediated cytolysis in porcine
      embryonic fibroblasts.
AB  - The expression of human complement regulatory proteins (CRP) and H-transferase
      (HT) in porcine cells is one of the strategies for suppression of hyperacute
      rejection (HAR) of xenotransplants in human recipients. In this study, we
      investigated the inhibitory effect of combined expression of human complement
      regulators and HT on human serum-mediated cytolysis in porcine embryonic
      fibroblasts. For the combinated expression of human CRPs in transformed pig
      cells, cDNAs of human DAF, MCP, and CD59 were cloned into the same insertional
      plasmid under the control of pCMV IE and LTR. The double combination of CRPs,
      hDAF-hMCP, and hMCP-hCD59 survived over 50% in the presence of 50% human serum,
      compared to the control. Moreover, the cell viability was increased more than 65%
      and 80% in the combination of human DAF-CD59 and DAF-MCP-CD59, respectively. In
      addition, the combination of HT gene to hDAF-hCD59 vector increased the viability
      close to 80%, similar to the triple combination of CRPs. These observations
      suggest that the combined expression of human CRPs and HT in the same insertional
      vector may be more effective in protecting porcine cells from human complement
      mediated cytolysis.

PMID- 16797370
TI  - Mycophenolic acid upregulates B7-DC expression on dendritic cells, which is
      associated with impaired allostimulatory capacity of dendritic cells.
AB  - In addition to its effects on lymphocytes, mycophenolic acid (MPA) may inhibit
      the allostimulatory capacity of dendritic cells (DC) via unknown mechanisms. B7
      H1 and B7-DC surface markers on DC negatively regulate T-cell responses via the
      receptor PD-1. In this study, we sought to investigate whether B7-H1 and B7-DC
      are responsible for the inhibitory functions of MPA on DC. Mouse bone marrow
      derived DC were cultured with recombinant granulocyte macrophage colony
      stimulating factor (GM-CSF) and interleukin (IL)-4 in the presence or absence of
      MPA (0.01 micromol and 0.1 micromol). The DC phenotype was assessed by flow
      cytometry, their immunostimulatory capacity measured by mixed lymphocyte reaction
      (MLR), and cytokine production by ELISA. The results showed that MPA not only
      inhibited the expression of major histocompatibility complex (MHC) class II and
      costimulatory molecules CD80 and CD86 but upregulated B7-DC expression on mature
      DC induced by LPS. These findings were associated with a reduced allostimulatory
      ability and an altered cytokine secretion pattern of DC. Thus, we suggest that
      MPA upregulates B7-DC expression during DC maturation induced by LPS in vitro, an
      effect that may be responsible for MPA-mediated inhibitory effects on the
      allostimulatory capacity of DC.

PMID- 16797371
TI  - Trafficking of donor-derived bone marrow correlates with chimerism and extension
      of composite allograft survival across MHC barrier.
AB  - We proposed to evaluate differences between recipient's immune response to
      vascularized skin and combined vascularized skin/bone allografts, under a 7-day
      alphabeta-TCR plus cyclosporine (CsA) treatment protocol. Thirty-six
      transplantations were performed in six groups: group I (isograft control
      vascularized skin graft; n=6); group II (isograft control-combined vascularized
      skin/bone graft; n=6); group III (allograft rejection control group-vascularized
      skin graft; n=6); group IV (allograft rejection control-combined vascularized
      skin/bone graft; n=6); group V (allograft treatment-vascularized skin graft;
      n=6); and group VI (allograft treatment-combined vascularized skin/bone graft;
      n=6). Isograft transplantations were performed between Lewis rats and allografts
      were transplanted across the MHC barrier from Brown Norway to Lewis rats. In the
      allograft treatment group, a combined alphabeta-TCR+CsA protocol was applied for
      7 days. All groups were compared clinically, immunologically and histologically.
      Statistical significance was determined with two-tailed Student's t test.
      Indefinite graft survival was achieved in the isograft control group (>300 days).
      Allograft rejection controls rejected within 5 to 9 days posttransplant;
      chimerism levels were undetectable (<.5%). Allografts under the alphabeta-TCR+CsA
      protocol had significantly extended survival when skin was combined with bone (61
      125 days) compared to vascularized skin allografts (43-61 days). Lymphoid
      macrochimerism was significantly higher in group VI than group V. Histology
      confirmed skin and bone viability. Combined vascularized skin/bone allografts had
      higher and sustained levels of donor-specific chimerism and extended allograft
      survival.

PMID- 16797372
TI  - Prolongation of renal allograft survival in rats by replication-defective
      recombinant adenovirus-mediated coexpression of CD40L and CTLA4Ig.
AB  - BACKGROUND: Blockade of costimulatory signals has been shown to prolong allograft
      survival. The aim of the present study was to investigate the effect of
      simultaneous blockade of CD40/CD40L and CD28/B7 costimulatory pathways by
      replication-defective adenovirus-mediated expression of secretable extracellular
      domain of human CD40L (shCD40L) and CTLA4Ig to prolong rats renal allograft
      survival. METHODS: We constructed Adv-shCD40L-IRES2-CTLA4Ig, a replication
      defective adenovirus carrying genes encoding human CD40L and CTLA4Ig.
      Coexpression of shCD40L and CTLA4Ig was evaluated by confocal laser scanning
      microscopy. The function of these two molecules was examined in human mixed
      lymphocyte reactions (MLRs) in vitro and in experimental BN-to-LEWIS rat renal
      transplantation in vivo. RESULTS: Successful construction of Adv-shCD40L-IRES2
      CTLA4Ig was confirmed by polymerase chain reaction. Coexpression of shCD40L and
      CTLA4Ig on human kidney cell line HK-2 cells after transfection was detected by
      direct immunofluorescence staining. Human MLR was inhibited to 52.2%+/-0.6% and
      42.1%+/-0.2% of the vehicle control by Adv-shCD40L and Adv-CTLA4Ig, respectively.
      Adv-shCD40L-IRES2-CTLA4Ig resulted in further inhibition of MLR to 22.0%+/-0.2%
      of vehicle control. Transfection with Adv-shCD40L or Adv-CTLA4Ig alone prolonged
      renal graft survival to 24.8+/-2.5 days and 27.3+/-3.6 days, respectively, as
      compared to vehicle-treated controls (7.8+/-0.3 days). Cotransfection of both
      genes extended graft survival to 41.8+/-3.7 days. CONCLUSIONS: Adv-shCD40L-IRES2
      CTLA4Ig, a replication-defective adenovirus carrying genes encoding human CD40L
      and CTLA4Ig, achieved simultaneous blockade of CD40/CD40L and CD28/B7
      costimulatory pathways, Adv-shCD40L-IRES2-CTLA4 by Ig synergistically inhibited
      human T-cell proliferation in MLR, and prolonged rats renal allograft survival.

PMID- 16797373
TI  - Optimizing a canine survival model of orthotopic lung transplantation.
AB  - INTRODUCTION: While acute models of orthotopic lung transplantation have been
      described in dogs, the technical considerations of developing a survival model in
      this species have not been elaborated. Herein, we describe optimization of a
      canine survival model of orthotopic lung transplantation. METHODS: Protocols of
      orthotopic left lung transplantation and single lung ventilation were established
      in acute experiments (n=9). Four dogs, serving as controls, received autologous,
      orthotopic lung transplants. Allogeneic transplants were performed in 16 DLA
      identical and 16 DLA-mismatched unrelated recipient dogs. Selective right lung
      ventilation was utilized in all animals. A Malecot tube was left in the pleural
      space connected to a Heimlich valve for up to 24 hours. To date, animals have
      been followed up to 24 months by chest radiography, pulmonary function tests,
      bronchoscopy with lavage, and open biopsies. RESULTS: Long-term survival was
      achieved in 34/36 animals. Two recipients died intraoperatively secondary to
      cardiac arrest. All animals were extubated on the operating table, and in all
      cases the chest tube was removed within 24 hours. Major complications included
      thrombosis of the pulmonary artery and subcritical stenosis of bronchial
      anastamosis. One recipient underwent successful treatment of a small bowel
      intussusception. CONCLUSIONS: We report our experience in developing a survival
      canine model of orthotopic single lung transplantation. While short-term survival
      following canine lung transplantation is achievable, we report particular
      considerations that facilitate animal comfort, early extubation, and lung
      reexpansion in the immediate postoperative period, further optimizing use of this
      species for experimental modeling of long-term complications after lung
      transplantation.

PMID- 16797375
TI  - New therapies in the treatment of breast cancer.
AB  - Systemic therapy for breast cancer is undergoing many interesting advances. In
      recent years, a better understanding of the underlying biology of cancer has led
      to the identification of several opportunities to target cellular pathways for
      therapeutic advantage. Hormonal therapy is often chosen as the first line of
      therapy because it is generally very well tolerated. However, most patients
      eventually become unresponsive to endocrine manipulation. Improved understanding
      of the mechanisms of hormonal resistance, and of the interplay between hormone
      receptors and cellular growth pathways, provides the rationale for combining
      signal transduction inhibitors and hormonal agents to overcome resistance.
      Emerging data from preclinical studies suggest that this goal might be achievable
      in the clinic. Antiangiogenic therapy has shown efficacy in colorectal and lung
      cancer and appears promising in breast cancer, although improved overall survival
      has not yet been shown. There have also been advances in cytotoxic chemotherapy.
      Reformulation of paclitaxel in polyoxy-castor-oil-free albumin nanoparticles (ABI
      007) has allowed more convenient, safer, and enhanced drug delivery with
      associated improvement in outcomes. New agents with novel mechanisms of action
      are also in development and appear to have activity in cancer cells that are
      resistant to currently available agents.

PMID- 16797376
TI  - Circulating tumor cells, disease progression, and survival in metastatic breast
      cancer.
AB  - Metastatic breast cancer (MBC) is considered incurable; therefore, palliative
      treatment is the only option. The biologic heterogeneity of the disease is
      reflected in its somewhat unpredictable clinical behavior. The presence of
      circulating tumor cells (CTCs) in patients with MBC about to start a new line of
      treatment has been shown to predict progression-free and overall survival. This
      prognostic value is independent of the line of therapy (eg, first or second
      line). Moreover, a multivariate analysis has shown the prognostic value of CTCs
      to be superior to that of site of metastasis, type of therapy, and length of time
      to recurrence after definitive primary surgery. These data suggest that the
      presence of CTCs may be used to modify the staging system for advanced disease.
      Larger studies are needed to confirm these data and evaluate the use of CTC
      detection in monitoring treatment and furthering our understanding of breast
      cancer biology when combined with other diagnostic technologies.

PMID- 16797377
TI  - Protein kinase C-beta as a therapeutic target in breast cancer.
AB  - Combining existing breast cancer therapies with novel agents that interfere with
      major signaling pathways is a promising approach. Targeting protein kinase C
      (PKC)-beta may serve as an attractive candidate in this regard for the following
      reasons: first, PKC-beta II (a splice variant of PKC-beta) has been implicated in
      tumorigenesis in human and rodent models. Second, PKC-beta, mainly PKC-betaII, is
      the predominant mediator of vascular endothelial growth factor-induced
      endothelial cell proliferation, which is a well-known stimulator of tumor
      angiogenesis and growth in breast cancer. There is increasing evidence that PKC
      beta-selective inhibitors are effective in both preclinical and clinical trials.
      Enzastaurin, a potent inhibitor of PKC-beta, suppresses both tumor growth and
      tumor-induced angiogenesis in human tumor xenografts. Phase II trials of
      enzastaurin in recurrent high-grade gliomas and lymphomas have shown promising
      results. A similar compound, ruboxistaurin, is also under investigation in
      clinical trials for diabetic complications. This review focuses on the rationale
      for using PKC-beta as a therapeutic target at both the preclinical and clinical
      levels in breast cancer.

PMID- 16797379
TI  - Use of pemetrexed in breast cancer.
AB  - Pemetrexed, a new antifolate drug, has shown broad-spectrum activity in multiple
      tumor types. Single-agent activity against breast cancer in untreated patients
      reached 31% and, depending on the type and degree of prior chemotherapy, response
      rates tended to decrease stepwise from 28% in lightly pretreated patients (ie,
      with only adjuvant chemotherapy or at maximum one chemotherapy treatment for
      metastatic disease) to 8% in heavily pretreated patients after exposure with
      anthracyclines, taxanes, and capecitabine. No clear dose-response relationship
      could be established. The results from an ongoing prospective, randomized, double
      blind phase II study of two different doses (600 mg/m(2) and 900 mg/m(2) of
      single-agent pemetrexed) may elucidate this further. In addition, analysis of
      specific gene profiles and clinical outcome with special emphasis on pathways
      known to be important for antifolate activity is ongoing. Combinations of
      pemetrexed with doxorubicin, epirubicin, or cyclophosphamide have also been
      evaluated in separate phase I/II trials. For the combination of pemetrexed with
      carboplatin or gemcitabine, dose recommendations from phase I trials that are not
      restricted to breast cancer have been used. The combination of pemetrexed with
      gemcitabine or carboplatin has shown remarkable activity. Further results on the
      use of a pemetrexed-plus-cyclophosphamide combination will be provided by an
      ongoing prospective, randomized phase II study.

PMID- 16797378
TI  - Overview of gemcitabine activity in advanced breast cancer.
AB  - Gemcitabine, an antimetabolite that is incorporated as a triphosphate into DNA,
      is active as a single agent in first- and subsequent-line treatment of breast
      cancer, with an overall objective response rate of 26%. It is relatively well
      tolerated, and its dose-limiting toxicity has usually been neutropenia.
      Gemcitabine has proven active in combination with paclitaxel and, on this basis,
      a phase III trial showed a significantly higher response rate than paclitaxel
      alone (39.3% v 25.6%). The combination also showed a significantly longer median
      time to progression (5.2 v 2.9 months) and significantly improved median overall
      survival time (18.5 v 15.8 months). Apart from neutropenia, there was no
      significant increase in toxicity for the combination. Gemcitabine has also been
      shown to be active in combination with docetaxel, and a phase III trial has shown
      that gemcitabine plus docetaxel is as effective as capecitabine plus docetaxel,
      but with significantly less nonhematologic toxicity. Two-week schedules of
      gemcitabine plus paclitaxel or docetaxel are currently being investigated, as are
      combinations with paclitaxel plus trastuzumab, and paclitaxel plus
      anthracyclines. These results have prompted ongoing trials of gemcitabine in
      early breast cancer as neoadjuvant and adjuvant therapy.

PMID- 16797380
TI  - Acute renal failure due to IgM-lambda glomerular thrombi and MPGN-like lesions in
      a patient with angioimmunoblastic T-Cell lymphoma.
AB  - A 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal
      failure. Laboratory data showed decreased levels of serum C3, C4, and CH50,
      elevated immunoglobulin M (IgM) levels, and the presence of cryoglobulinemia (IgM
      lambda). Renal biopsy showed membranoproliferative glomerulonephritis-like
      lesions with azan-red-stained thrombi in the glomerular capillary lumen.
      Immunofluorescence showed that IgM-lambda stained strongly in the glomerular
      capillary lumen, equal to the azan-red-stained thrombi, whereas C3 and C4
      staining was negative. Electron microscopy showed electron-dense deposits in the
      subendothelial space and glomerular thrombi lacking fine fibrillar structure.
      These findings suggest that cryoglobulin, which consists of monoclonal IgM
      lambda, induced glomerular thrombi and acute renal failure in a patient with
      angioimmunoblastic T-cell lymphoma.

PMID- 16797381
TI  - Association of uteroglobin G38A polymorphism with IgA nephropathy: a meta
      analysis.
AB  - Both uteroglobin knockout and antisense transgenic mice develop pathological and
      clinical features similar to immunoglobulin A (IgA) nephropathy. However, several
      association studies of uteroglobin G38A polymorphism and IgA nephropathy showed
      controversial findings. We used meta-analysis to assess the impact of the
      uteroglobin G38A polymorphism on susceptibility to and progression of IgA
      nephropathy. Six studies involving uteroglobin G38A genotyping of 930 patients
      with IgA nephropathy and 768 healthy controls were included. No significant
      publication bias was found (Egger's linear regression, P = 0.763; 95% confidence
      interval [CI], -0.610 to 0.476). All control samples were in Hardy-Weinberg
      proportion. No association between the AA genotype and risk for IgA nephropathy
      relative to both other genotypes (odds ratio [OR], 1.05; 95% CI, 0.71 to 1.54) or
      A allele and risk for IgA nephropathy (OR, 0.96; 95% CI, 0.84 to 1.11) were shown
      in the total meta-analysis. In both Asian and European subgroups, the overall
      effect of the AA genotype and A allele also showed no significant difference.
      There also was no significant association between uteroglobin AA genotype or A
      allele and IgA nephropathy progression (OR, 3.62; 95% CI, 0.59 to 22.34; OR,
      2.19, 95% CI, 0.37 to 13.14, respectively). We suggest that uteroglobin G38A
      polymorphism is not related to the development and progression of IgA
      nephropathy.

PMID- 16797382
TI  - Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in
      proteinuric renal disease: a systematic review of the efficacy and safety data.
AB  - Blockade of the renin-angiotensin system with either an angiotensin-converting
      enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) was shown to
      decrease urinary protein excretion and slow the progression of both diabetic and
      nondiabetic proteinuric renal disease. The safety and efficacy of combined ACE
      inhibitor and ARB therapy is not well established. We conducted a systematic
      review and meta-analysis of randomized trials evaluating the combination of an
      ACE inhibitor and an ARB in patients with chronic proteinuric renal disease.
      Twenty-one randomized controlled studies (n = 654 patients) were identified using
      MEDLINE, EMBASE, and Cochrane Central databases. Five trials had a parallel-group
      design and 16 trials used a crossover design. Combination therapy with an ACE
      inhibitor and an ARB resulted in a small, but significant, increase in serum
      potassium levels (weighted mean difference, 0.11 mEq/L [0.11 mmol/L]; 95%
      confidence interval [CI], 0.05 to 0.17) and a nonsignificant decrease in
      glomerular filtration rate (weighted mean difference, 1.4 mL/min [0.02 mL/s]; 95%
      CI, -2.6 to 0.2). Addition of an ARB resulted in a further decrease in
      proteinuria (weighted mean difference, 440 mg/d; 95% CI, 289 to 591) compared
      with an ACE inhibitor alone. This effect was observed in patients with diabetic
      (210 mg/d; 95% CI, 84 to 336) and nondiabetic (582 mg/d; 95% CI, 371 to 793)
      renal disease. In conclusion, the combination of ACE-inhibitor and ARB therapy in
      patients with chronic proteinuric renal disease is safe, without clinically
      meaningful changes in serum potassium levels or glomerular filtration rates.
      Combination therapy also was associated with a significant decrease in
      proteinuria, at least in the short term. Additional trials with longer follow-up
      are needed to determine whether the decrease in proteinuria will result in
      significant preservation of renal function.

PMID- 16797383
TI  - Maximal cardiovascular fitness and its correlates in ambulatory hemodialysis
      patients.
AB  - BACKGROUND: Studies focusing on maximal cardiovascular fitness in ambulatory
      hemodialysis patients are lacking. The main purpose of this study is to look at
      maximal cardiovascular fitness in ambulatory hemodialysis patients, and the
      secondary purpose is to look at correlates with such fitness. METHODS: We studied
      maximal cardiovascular fitness in ambulatory hemodialysis patients and age
      matched controls. Correlates of maximal oxygen consumption with functional and
      physical performance, psychiatric symptoms, cognitive function, quality of life,
      duration of dialysis therapy, and adequacy of dialysis also were examined.
      RESULTS: We found ambulatory hemodialysis patients to have 72% to 79% of physical
      performance and 71% of maximal oxygen consumption compared with age-matched
      controls. In ambulatory hemodialysis patients, maximal oxygen consumption
      correlated not only with age and physical performance (the distance walked in a 6
      minute walk test, bilateral handgrip strength, and chair-rising time), but also
      with a psychiatric symptom (losing confidence in oneself) and quality of life
      (feeling safe in one's daily life). However, multiple regression analysis showed
      that chair-rising time was the only variable that correlated negatively with
      maximal oxygen consumption in ambulatory hemodialysis patients. CONCLUSION: Based
      on the relatively poor maximal cardiovascular fitness in ambulatory hemodialysis
      patients compared with age-matched controls, an additional fitness training
      program for these patients is needed.

PMID- 16797384
TI  - Improving albumin levels among hemodialysis patients: a community-based
      randomized controlled trial.
AB  - BACKGROUND: Low albumin level is a strong predictor of mortality and morbidity
      among hemodialysis patients, yet few interventions are available to improve
      albumin levels. Moreover, the relative importance of nutritional barriers versus
      inflammation in contributing to hypoalbuminemia is unclear. We sought to
      determine whether targeting specific nutritional barriers will improve albumin
      levels. METHODS: We conducted a randomized controlled trial involving 180
      patients with baseline albumin levels less than 3.7 g/dL (<37 g/L) at 44 long
      term hemodialysis facilities. Study coordinators identified and intervened on
      specific barriers present among intervention patients, whereas control patients
      continued to receive the usual care. Barriers targeted included poor nutritional
      knowledge, poor appetite, help needed with shopping or cooking, low fluid intake,
      inadequate dialysis dose, depression, difficulty chewing, difficulty swallowing,
      gastrointestinal symptoms, and acidosis. RESULTS: At baseline, intervention and
      control patients had similar albumin levels, dietary intakes, levels of
      inflammatory markers, and numbers of nutritional barriers. After 12 months,
      intervention patients had greater increases in albumin levels compared with
      control patients (+0.21 versus +0.06 g/dL [+2.1 versus +0.6 g/L]; P < 0.01), as
      well as greater increases in energy intake (+4.1 versus -0.6 Kcal/d/kg; P <
      0.001) and protein intake (+0.13 versus -0.06 g/d/kg; P < 0.001). The
      intervention appeared most effective for barriers related to poor nutritional
      knowledge, help needed with shopping or cooking, and difficulty swallowing. About
      half the subjects had elevated levels of inflammatory markers, but there was no
      relationship between change in levels of albumin and inflammatory markers.
      CONCLUSION: A nutrition intervention tailored to patient-specific barriers
      resulted in modest improvements in albumin levels regardless of levels of
      inflammatory markers.

PMID- 16797385
TI  - Longitudinal associations between dietary protein intake and survival in
      hemodialysis patients.
AB  - BACKGROUND: Decreased dietary protein intake may be associated with increased
      mortality risk in individuals with kidney failure undergoing maintenance
      hemodialysis (MHD). We hypothesized that longitudinal changes in dietary protein
      intake have independent associations with survival in MHD patients. METHODS: The
      relation between urea kinetic-based normalized protein nitrogen appearance (nPNA)
      and all-cause and cardiovascular mortality was examined in a 2-year (July 2001 to
      June 2003) cohort of 53,933 MHD patients from virtually all DaVita dialysis
      clinics in the United States, using both conventional and time-dependent
      (repeated-measure) Cox models to estimate death hazard ratios for quarterly
      averaged nPNA categories controlled for case-mix, comorbidity, dialysis dose
      (Kt/V), and available markers of malnutrition-inflammation complex syndrome
      (MICS). RESULTS: The best survival was associated with nPNA between 1.0 and 1.4
      g/kg/d, whereas nPNA less than 0.8 or greater than 1.4 g/kg/d was associated with
      greater mortality in almost all models. Adjustment for MICS mitigated the
      associations substantially. A decrease in protein intake during the first 6
      months in patients with an nPNA in the 0.8- to 1.2-g/kg/d range was associated
      incrementally with greater death risks in the subsequent 18 months, whereas an
      increase in nPNA tended to correlate with reduced death risk. CONCLUSION: Low
      daily protein intake or decrease in its magnitude over time is associated with
      increased risk for death in MHD patients. Whether the association between time
      varying protein intake and survival is causal or a consequence of anorexia
      secondary to MICS or other factors needs to be explored further in interventional
      trials.

PMID- 16797386
TI  - Obesity is associated with family history of ESRD in incident dialysis patients.
AB  - BACKGROUND: Obesity is an established risk factor for chronic kidney disease and
      aggregates in families. The objective of this study is to examine the
      relationship between obesity and family history of end-stage renal disease
      (ESRD). METHODS: Data were collected from 25,883 incident patients with ESRD in
      US ESRD Network 6 (Georgia, North Carolina, and South Carolina) dialysis clinics
      between 1995 and 2003. Family history is defined as a first- or second-degree
      relative with ESRD. Body mass index (BMI) at dialysis therapy initiation was
      classified as underweight (BMI < 18.5 kg/m2), normal (BMI, 18.5 to <25 kg/m2),
      overweight (BMI, 25 to < 30 kg/m2), obese (BMI, 30 to <35 kg/m2), or morbidly
      obese (BMI > or = 35 kg/m2). RESULTS: Twenty-three percent of patients reported a
      family history of ESRD. Of patients reporting a family history of ESRD, 5.5% were
      underweight, 32.5% had normal BMI, 28.0% were overweight, 17.3% were obese, and
      16.7% were morbidly obese. After controlling for age, race, sex, primary cause of
      ESRD, history of diabetes, history of hypertension, and estimated glomerular
      filtration rate at dialysis therapy initiation, reported family history of ESRD
      was associated with being overweight (odds ratio [OR], 1.17; 95% confidence
      interval [CI], 1.08 to 1.26), obese (OR, 1.25; 95% CI, 1.14 to 1.37), and
      morbidly obese (OR, 1.40; 95% CI, 1.27 to 1.55). CONCLUSION: Obesity at dialysis
      therapy initiation was associated independently with reported family history of
      ESRD. This finding suggests that behavioral factors, adiposity-related genes, and
      gene-by-BMI interaction may contribute to familial risk for ESRD. This finding
      also suggests that management of obesity may be even more important for patients
      with a family history of ESRD than for the general population.

PMID- 16797388
TI  - Therapeutic effect of topical gamma-linolenic acid on refractory uremic pruritus.
AB  - BACKGROUND: Pruritus is a bothersome symptom affecting up to 80% of dialysis
      patients. Lymphocyte and cytokine interaction has an important role in the
      pathogenesis of uremic pruritus. Gamma-linolenic acid (GLA) is associated with
      immune modulation of T lymphocytes and lymphokines. The aim of this study is to
      determine whether topical GLA can attenuate uremic pruritus. METHODS: Seventeen
      dialysis patients with refractory uremic pruritus who passed the screening
      criteria entered a prospective, randomized, double-blind, placebo-controlled,
      crossover study. They stopped all antipruritic therapy at least 2 weeks before
      the study and were randomly assigned to treatment with either GLA 2.2% cream or
      placebo-based cream applied to the entire body after taking a bath once a day and
      to pruritic sites 3 times a day for 2 weeks, and then the reverse treatment after
      a 2-week washout period. Severity of pruritus was evaluated by using a
      traditional visual analogue scale (VAS) and a modified questionnaire method
      (pruritus score [PS]). Hemogram, aspartate and alanine aminotransferases,
      bilirubin, albumin, blood urea nitrogen, creatinine, calcium, phosphate, and
      intact parathyroid hormone were measured. RESULTS: Sixteen patients completed the
      study; 1 patient was withdrawn because of an allergic skin reaction. There were
      no significant differences between groups except for sex distribution. Median VAS
      and PS values between groups did not differ significantly at baseline. There is a
      greater antipruritic effect of GLA based on evaluation with both the VAS and PS.
      There is persistence of a residual effect into the second treatment period after
      GLA treatment. CONCLUSION: GLA-rich cream is better than placebo-based cream for
      alleviating uremic pruritus. It is a useful adjuvant in the management of
      refractory uremic pruritus.

PMID- 16797387
TI  - Serum myeloperoxidase and mortality in maintenance hemodialysis patients.
AB  - BACKGROUND: During inflammation, myeloperoxidase (MPO) is released, for which its
      measurement in systemic circulation may be used as an index of leukocyte
      activation and oxidant stress. MPO levels correlate with angiographic evidence of
      coronary atherosclerosis and cardiovascular events in subjects with chest pain
      within the general population. We hypothesized that serum MPO levels are
      associated with adverse clinical outcomes in maintenance hemodialysis (MHD)
      patients. METHODS: MPO levels were determined in serum samples from 356 MHD
      patients at the start of a 3-year cohort. RESULTS: Patients (46% women, 28%
      blacks, 54% with diabetes) were 54.6 +/- 14.6 (SD) years old and had undergone
      MHD for a median period of 26 months. Measured serum MPO level was 2,005 +/-
      1,877 pmol/L (median, 1,444 pmol/L; interquartile range, 861 to 2,490 pmol/L).
      MHD patients with greater total body fat had greater MPO levels. MPO level had
      statistically significant (P < 0.01) and positive correlations with values for
      serum C-reactive protein (CRP; r = +0.15), interleukin 6 (IL-6; r = +0.23), tumor
      necrosis factor alpha (TNF-alpha; r = +0.21), and white blood cell count (r =
      +0.21). A death hazard ratio for each 1,000-pmol/L increase in serum MPO level
      was 1.14 (95% confidence interval [CI], 1.03 to 1.26; P = 0.01) after controlling
      for age, race (black), diabetes mellitus, dialysis vintage, Charlson comorbidity
      score, history of previous cardiovascular disease, blood hemoglobin level, and
      serum concentrations of albumin, CRP, IL-6, and TNF-alpha. After dividing MPO
      values into 3 equal groups (tertiles), the death hazard ratio of the highest
      tertile (versus the middle tertile) was 1.82 (95% CI, 1.07 to 3.10; P = 0.03).
      CONCLUSION: Serum MPO levels correlate with levels of markers of inflammation and
      prospective mortality risk in MHD patients.

PMID- 16797389
TI  - Factors influencing route of administration for epoetin treatment among
      hemodialysis patients in the United States.
AB  - BACKGROUND: Published clinical guidelines advocate subcutaneous (SC)
      administration for epoetin therapy, although this is practiced among only 7% of
      all hemodialysis patients. Despite this disparity, few studies have examined
      factors associated with route of epoetin administration in hemodialysis patients.
      METHODS: Data from the Centers for Medicare & Medicaid Services End-Stage Renal
      Disease Clinical Performance Measures Project were used to identify 13,854
      patients receiving hemodialysis in 3,069 dialysis facilities from October to
      December in 1999 and 2000. Unadjusted associations were examined by using t-test
      and chi-square test. Adjusted associations were estimated by using generalized
      estimating equations to control for clustering of patients within the same
      dialysis facility. RESULTS: In the United States, use of the SC route of epoetin
      administration varies widely across the country. After adjusting for patient
      sociodemographics and comorbidities, the greatest rates of SC therapy are found
      in the Midwest and West, in providers not affiliated with chains, and in hospital
      based and not-for-profit freestanding units. Previous exposure to SC
      administration (as a predialysis or peritoneal dialysis patient) predicted
      subsequent SC use, for-profit and large chains were significantly less likely to
      use SC administration, and increased use of injectable drugs overall (to maximize
      income) was associated with less SC use. CONCLUSION: In addition to regional
      variation in SC use, study findings indicate that physician decision making for
      epoetin administration route is influenced primarily by type of ownership and
      financial incentives. Adherence to published clinical guidelines was not a
      consistent predictor of SC use. Given the similar effectiveness, but
      significantly decreased dose associated with SC epoetin, these findings suggest
      an enormous opportunity for cost savings for the Medicare program.

PMID- 16797390
TI  - Arterial steal syndrome: a modest proposal for an old paradigm.
AB  - BACKGROUND: Access ligation has been considered to be the treatment for patients
      presenting with arterial steal syndrome by many nephrologists. We report results
      of a prospective study using comprehensive arteriography coupled with
      percutaneous transluminal balloon angioplasty (PTA) or surgical intervention to
      evaluate and manage steal syndrome. METHODS: Twelve consecutive patients referred
      for symptoms of steal syndrome were examined. Comprehensive arteriography of the
      extremity to diagnose arterial stenoses and delineate anatomy was performed by
      advancing a diagnostic catheter into the subclavian artery. Findings of
      arteriography and degrees of stenosis before and after PTA also were documented.
      Resolution of symptoms after PTA and surgical interventions, as well as
      complications, were recorded. RESULTS: Angiography showed arterial stenotic
      lesions in 10 of 12 patients (83%). The degree of stenosis was 66% +/- 14% (SD).
      Eight patients (80%) with stenotic lesions underwent PTA successfully. The degree
      of stenosis after PTA was 13% +/- 10%. The remaining 2 patients were not
      considered candidates for PTA and were referred to surgery with arteriography
      images. One patient underwent ligation and the other patient required an axillary
      loop fistula using the same outflow vein. The 2 patients without stenoses showed
      excessive steal through the anastomosis and underwent lengthening procedures by
      insertion of a vein segment. All 12 patients are symptom free with a mean follow
      up of 8.3 +/- 4 months, and 11 of 12 patients (92%) are dialyzing using the same
      access. There were no procedure-related complications. CONCLUSION: We suggest
      that complete imaging of the arterial circulation of the extremity be considered
      in patients presenting with symptoms of steal syndrome to properly assess the
      arterial anatomy and develop a treatment strategy.

PMID- 16797391
TI  - Inflow stenoses in dysfunctional hemodialysis access fistulae and grafts.
AB  - BACKGROUND: The aim of the study is to prospectively determine the incidence of
      inflow stenoses in dysfunctional hemodialysis access arteriovenous fistulae
      (AVFs) and grafts (AVGs). METHODS: Contrast-enhanced magnetic resonance
      angiography (CE-MRA) was performed of 66 dysfunctional AVFs and 35 AVGs in 56 men
      and 45 women (mean age, 62 years; age range, 31 to 86 years). Complete inflow
      (from the subclavian artery), shunt region, and complete outflow (including
      subclavian vein) were shown at CE-MRA. In addition to standard digital
      subtraction angiography (DSA) of the shunt region and outflow, DSA of the
      complete inflow was obtained through access catheterization of all cases in which
      CE-MRA showed an inflow stenosis. Vascular stenosis is defined as greater than
      50% decrease in luminal diameter compared with an uninvolved vascular segment
      located adjacent to the stenosis. Endovascular intervention of stenoses was
      performed in connection with DSA. RESULTS: CE-MRA showed 19 arterial stenoses in
      14 patients (14%). DSA confirmed 18 of these lesions in 13 patients and showed no
      additional inflow lesions. Of the 13 patients, 7 patients had arterial stenoses
      only and 6 patients had accompanying stenoses in the shunt region and/or outflow.
      Referral criteria for the 13 patients to undergo access evaluation had been
      decreased flow rates (9 patients), steal symptoms (2 patients), and insufficient
      access maturation (2 patients). Access flow of the 9 patients with a low-flow
      access improved from 477 +/- 74 mL/min to 825 +/- 199 mL/min after angioplasty.
      One patient with steal symptoms became symptom free after angioplasty.
      Endovascular intervention in 3 patients proved to be unsuccessful. CONCLUSION:
      Inflow stenoses are not uncommon in dysfunctional hemodialysis access shunts. We
      suggest that radiological evaluation comprise assessment of the complete arterial
      inflow.

PMID- 16797392
TI  - Renal osteodystrophy: alpha-Heremans Schmid glycoprotein/fetuin-A, matrix GLA
      protein serum levels, and bone histomorphometry.
AB  - BACKGROUND: Fetuin-A of hepatic origin circulates in large amounts in serum, but
      also is expressed in bone, where it is an inhibitor of transforming growth factor
      beta (TGF-beta)/bone morphogenetic protein (BMP) proteins. Together with matrix
      GLA protein (MGP), fetuin-A is able to make up a complex with calcium and
      phosphate that is more soluble than calcium and phosphate alone, preventing its
      deposition in extraskeletal tissues. Experimental results suggested that this
      complex is made at bone tissue level. The aim of this study is to evaluate
      whether serum fetuin-A and MGP are influenced by type of renal osteodystrophy,
      they correlate with bone histomorphometric and histodynamic parameters, and/or
      serum levels may influence bone turnover. METHODS: Thirty-eight hemodialysis
      patients who volunteered to undergo a bone biopsy were studied. Patients (27 men,
      11 women) had a mean age of 55.2 +/- 11.8 years and dialysis vintage of 75.7 +/-
      57.4 months. They were not administered vitamin D or drugs connected with mineral
      metabolism. They underwent transiliac bone biopsy after tetracycline labeling.
      Biopsies were performed for histological, histomorphometric, and histodynamic
      evaluation and aluminum histochemistry. Serum fetuin-A and MGP were measured by
      using enzyme-linked immunosorbent assay kits. RESULTS: Serum fetuin-A levels were
      significantly less than normal, whereas MGP levels were less than the normal
      average. Fetuin-A levels in patients with hyperparathyroidism, mixed
      osteodystrophy, and low-turnover osteodystrophy were 0.219 +/- 0.1, 0.27 +/- 0.1,
      and 0.197 +/- 0.1 ng/mL, respectively (P = not significant). Fetuin-A level
      significantly correlated inversely with values for several histomorphometric
      parameters, such as osteoid volume (OV/BV), osteoblastic surface (Ob.S/BS),
      osteoid surface (OS/BS), and osteoclastic surface (Oc.S/BS). Logistic regression
      showed odds ratios of 5.3 and 4.9 for the association of high fetuin-A levels
      with low values for OS/BS and Ob.S/BS, respectively. Results of multiple
      regression analysis with intact parathyroid hormone and fetuin-A levels as
      independent variables and OV/BV and Ob.S/BS as dependent variables showed that
      independent variables correlated significantly with dependent variables,
      positively for intact parathyroid hormone levels and inversely for fetuin-A
      levels. MGP levels in patients with hyperparathyroidism, mixed osteodystrophy,
      and low-turnover osteodystrophy were not significantly different (3.94 +/- 0.86,
      3.40 +/- 0.99, and 5.64 +/- 2.4 nmol/L, respectively). By dividing MGP serum
      values into tertiles, mean values for OV/BV were different (analysis of variance,
      P < 0.04), with a greater value in the higher MGP tertile. By exclusion of 3
      extravariant cases (>3 SDs greater than the mean), 1 case for each type of
      osteodystrophy, a significant correlation between bone formation rate and MGP
      serum level was found (P < 0.05). In addition, a significant correlation was
      found between MGP level and trabecular thickness. CONCLUSION: Fetuin-A and MGP
      levels correlated with bone formation parameters. This association could be
      caused by an effect of these proteins on bone formation, presumably mediated by
      the TGF-beta/BMP system. Fetuin-A, as opposed to MGP, is known to inhibit the TGF
      beta/BMP complex, a protein-cytokine system that appears to be an important
      regulator of bone formation and probably a factor with an important role in renal
      osteodystrophy.

PMID- 16797393
TI  - Initial dosing of paricalcitol based on PTH levels in hemodialysis patients with
      secondary hyperparathyroidism.
AB  - BACKGROUND: Adjustment of the initial dose of paricalcitol in hemodialysis
      patients with secondary hyperparathyroidism (SHPT) on the basis of severity of
      SHPT generally is preferred in current practice. Whether the proposed dose, based
      on the formula baseline intact parathyroid hormone (iPTH [picograms per
      milliliter]) divided by 80, is the most appropriate has not been assessed
      adequately. METHODS: A double-blind randomized trial comparing iPTH/80 dose with
      the immediately lower iPTH/120 dose was undertaken. Forty-three hemodialysis
      patients with iPTH levels between 300 and 900 pg/mL (300 and 900 ng/L) were
      followed up for 12 weeks. The primary outcome was control of iPTH levels within a
      target range between 150 and 300 pg/mL (150 and 300 ng/L). RESULTS: No difference
      between the 2 dose groups was noted in time to achieve target iPTH levels of 150
      to 300 pg/mL (150 to 300 ng/L). More episodes of excessive decrease in iPTH
      levels occurred in the iPTH/80 group compared with the iPTH/120 group (P =
      0.003). Nine patients in the iPTH/80 group (45%) versus 2 patients in the
      iPTH/120 group (10%) had iPTH levels less than 150 pg/mL (<150 ng/L) in at least
      half the measurements performed during the second half of the study (P = 0.034).
      Increases in calcium levels were greater in the iPTH/80 group at all times during
      the study (P < 0.05 at weeks 4 and 10). The number of required dose reductions
      was significantly greater in the iPTH/80 group compared with the iPTH/120 group
      (P = 0.008). CONCLUSION: In hemodialysis patients with SHPT, a lower initial dose
      of iPTH/120 shows efficacy similar to that of the already widely used iPTH/80
      scheme in reaching target iPTH levels (150 to 300 pg/mL [150 to 300 ng/L]), with
      less required dose adjustments, lower increase in calcium levels, and lower cost.
      In addition, the initial dose of paricalcitol based on the iPTH/80 formula leads
      significantly more patients to excessive suppression of iPTH (<150 pg/mL [<150
      ng/L]) than the iPTH/120 dose.

PMID- 16797394
TI  - Advance care planning by or on behalf of peritoneal dialysis patients in long
      term care.
AB  - BACKGROUND: Advance care planning (ACP) is recommended for dialysis patients,
      especially those living in long-term-care facilities. Factors influencing ACP and
      the effect of plans on outcome are incompletely studied. METHODS: We performed a
      retrospective chart review and follow-up of all peritoneal dialysis patients
      admitted to an academic nursing home between 1986 and 2000 and abstracted
      demographics, comorbidities, functional status as activities of daily living
      (ADL) score, documentation of ACP, and actual interventions. RESULTS: Of 109
      patients, 108 had ACP; of these, patients participated in 71%. Plans to do not
      attempt resuscitation (DNAR) were associated with the presence of coronary
      disease (odds ratio, 4.24; confidence interval [CI], 1.49 to 12.02), lower ADL
      score (odds ratio, 1.22; CI, 1.08 to 1.38), and older age (odds ratio, 1.04; CI,
      1.0007 to 1.09). Plans to do not hospitalize (DNH) were associated with ADL score
      only (odds ratio, 1.26; CI, 1.07 to 1.48). Patients with DNAR plans had poorer 3
      , 6-, and 12-month survival (P < 0.02), but not after adjustment for age of 75
      years or older, poor functional status, coronary disease, and decubiti. Plan
      compliance was limited. DNH plans were not associated with the likelihood of
      hospitalization (5 of 14 versus 42 of 93 patients) or length of stay (11.0 +/-
      16.4 versus 8.0 +/- 15.1 days). Compliance with DNAR plans was determined for 81
      of 108 patients. No patient with a DNAR plan had resuscitation attempted. Only 7
      of 46 patients with plans to undergo resuscitation had it attempted. CONCLUSION:
      For these chronically ill patients, age and functional status strongly influence
      DNAR and DNH plans. ACP was not decisive in determining events during acute
      illness.

PMID- 16797395
TI  - Treatment of erectile dysfunction with sildenafil citrate in renal allograft
      recipients: a randomized, double-blind, placebo-controlled, crossover trial.
AB  - BACKGROUND: Erectile dysfunction (ED) is observed frequently in patients with end
      stage renal disease, hemodialysis patients, and renal allograft recipients. There
      are few studies of sildenafil use in renal allograft recipients. METHODS: The
      study is designed as a randomized, double-blind, placebo-controlled, crossover
      trial. Efficacy was assessed by using the self-administered International Index
      of Erectile Function (IIEF), a 15-question validated measure of ED, and a global
      efficacy question (Did the treatment improve your erection?). RESULTS: Thirty-two
      eligible renal transplant recipients were included in this study. After treatment
      with sildenafil citrate, patients had significantly better scores in 13 of 15
      questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire
      level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration
      ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly
      better after sildenafil therapy. There were no significant differences between
      baseline and post-placebo treatment scores, except for question 13 (relationship
      satisfaction). Patients treated with sildenafil had significantly better scores
      in 4 domains compared with baseline, but a difference was not observed in the
      sexual desire domain (P = 0.32). There were no significant differences in scores
      between placebo and baseline in any domain. On the global efficacy question,
      81.3% of patients showed improvement compared with 18.7% with placebo. There were
      no differences in areas under the curve and maximum cyclosporine concentrations
      before and after sildenafil therapy. No patient discontinued the drug because of
      side effects except for 1 patient with visual hallucination. CONCLUSION:
      Treatment with sildenafil in renal transplant recipients is a valid option with
      an effective response.

PMID- 16797396
TI  - Impact of metabolic syndrome on graft function and survival after cadaveric renal
      transplantation.
AB  - BACKGROUND: The prevalence and consequences of metabolic syndrome after renal
      transplantation are not well established. Our aims are to analyze in a historic
      cohort of consecutive renal transplant recipients without diabetes: (1) the
      prevalence of metabolic syndrome and its evolution to de novo posttransplantation
      diabetes mellitus (PTDM), and (2) its impact on graft function and graft and
      patient survival. METHODS: We studied 230 transplant recipients with stable graft
      function at 1 year (baseline) and at least 18 months of follow-up (assessment
      date). Metabolic syndrome is defined using the Adult Treatment Panel III criteria
      with a slight modification. RESULTS: Metabolic syndrome was present in 22.6% of
      transplant recipients at baseline, increasing to 37.7% at assessment date.
      Transplant recipients with metabolic syndrome at baseline more frequently
      developed PTDM during follow-up than those without metabolic syndrome (P <
      0.001). In multiple linear regression analysis, metabolic syndrome was an
      independent risk factor for decreasing inverse serum creatinine (1/Cr) during
      follow-up (P = 0.038). In Cox proportional analysis, the hazard ratio for a 30%
      decrease in 1/Cr over time was 2.6 (95% confidence interval, 1.3 to 5.1; P =
      0.005). Graft survival was significantly lower in the metabolic-syndrome group (P
      = 0.008) and remained significant in multivariate Cox analysis (hazard ratios, 3
      to 4.5 in different models). Patient survival also was significantly lower in the
      metabolic-syndrome group (P = 0.02). CONCLUSION: Metabolic syndrome is a
      prominent risk factor for PTDM, chronic graft dysfunction, graft loss, and
      patient death in renal transplant recipients. Because metabolic syndrome is a
      cluster of modifiable factors, prompt intervention may prevent its consequences.

PMID- 16797397
TI  - Loss of podocyte dysferlin expression is associated with minimal change
      nephropathy.
AB  - We report a case of limb-girdle muscular dystrophy type 2B (LGMD2B) associated
      with minimal change disease. Immunohistochemical examination of quadriceps muscle
      showed a deficiency in dysferlin in sarcolemma, and dysferlin gene analysis
      showed 3370 G missense mutation, leading us to the diagnosis of LGMD2B. The
      patient also developed glomerular proteinuria. We also explored urinary protein
      levels in 3 other patients with dysferlinopathy and found microalbuminuria with
      albumin excretion of 0.14 to 0.18 g/d in 2 patients. Renal abnormalities during
      LGMD2B and kidney dysferlin expression have never been reported. Renal biopsy
      showed a lack of glomerular dysferlin expression compared with a positive
      immunohistochemical marking in patients with idiopathic minimal change
      nephropathy and healthy controls. We therefore suggest that dysferlin is present
      in glomeruli and may be associated with glomerular permeability.

PMID- 16797398
TI  - Successful treatment of a patient with severe calcific uremic arteriolopathy
      (calciphylaxis) by etidronate disodium.
AB  - A 59-year-old woman with a 10-year history of hemodialysis was admitted to our
      hospital for painful skin ulcers on her right thigh, right calf, and left upper
      arm. A whole-body plain computed tomographic scan showed diffuse calcification of
      the uterus and marked calcification of the mitral valve. Skin biopsy specimens
      from the left thigh showed calcium deposition in numerous small blood vessels in
      the dermis and fat, leading to a diagnosis of calcific uremic arteriolopathy
      (CUA). Despite antibiotic therapy and aggressive wound care for 2 months, the
      skin ulcers enlarged and the patient's general condition worsened. Surprisingly,
      oral administration of etidronate disodium (200 mg/d) strikingly improved the
      focal infection and decreased the size of the skin ulcers within several days.
      She was discharged from the hospital 2 months later, when epithelialization of
      the ulcers was almost complete. We report a case of CUA that was improved
      dramatically by treatment with etidronate. Etidronate therapy should be
      considered for refractory CUA.

PMID- 16797400
TI  - Surrogate markers in clinical studies: problems solved or created?

PMID- 16797399
TI  - A rare case of combined syndrome of inappropriate antidiuretic hormone secretion
      and Fanconi syndrome in an elderly woman.
AB  - An 83-year-old Japanese woman was admitted to our hospital with severe
      hyponatremia (sodium, 108 mEq/L [108 mmol/L]), hypokalemia, hypochloridemia,
      hypocalcemia, hypophosphatemia, and hypouricemia. Despite low plasma osmolarity
      (232 mOsm/kg [232 mmol/kg]), urine osmolarity (320 mOsm/kg) was greater than that
      of plasma, and she had increased urinary sodium excretion (88 mEq/L [88 mmol/L])
      and an unsuppressed high plasma level of antidiuretic hormone (ADH; 5.5 pg/mL
      [5.1 pmol/L]). These findings indicated that she had syndrome of inappropriate
      ADH secretion (SIADH). In addition, she had a generalized reabsorption defect of
      the proximal tubules, including decreased tubular reabsorption of phosphate,
      increased fractional excretion of uric acid, glycosuria despite a normal blood
      glucose level, and panaminoaciduria. Thus, combined SIADH and Fanconi syndrome
      was diagnosed. The cause was thought to be the antidepressant paroxetine, which
      is a selective serotonin reuptake inhibitor (SSRI). Several of the abnormal
      values resolved within 1 week after discontinuation of this drug. Although the
      precise mechanism responsible was not elucidated, we report an extremely rare
      case of combined SIADH and Fanconi syndrome, probably caused by short-term SSRI
      therapy.

PMID- 16797401
TI  - Improving physical functioning: time to be a part of routine care.

PMID- 16797402
TI  - Improving albumin levels among hemodialysis patients.

PMID- 16797403
TI  - Diffuse glomerular crescents and peritubular immune deposits in a transplant
      kidney.

PMID- 16797405
TI  - More infiltration in less mature fistulae?

PMID- 16797406
TI  - Relevance of aluminum screening in 2006.

PMID- 16797408
TI  - Revisiting the role of dose intensity in hematological malignancies.

PMID- 16797409
TI  - Immunosuppressive therapy for acquired severe aplastic anemia (SAA): a
      prospective comparison of four different regimens.
AB  - OBJECTIVE: This study was designed to investigate four different
      immunosuppressive therapy (IST) regimens as treatment of acquired severe aplastic
      anemia (SAA). PATIENTS AND METHODS: 142 consecutive SAA patients were randomized
      to receive one of the following IST regimens: equine anti-human thymocyte
      immunoglobulin (E-ATG) alone (IST regimen I); E-ATG and cyclosporine A (CSA) (IST
      regimen II); E-ATG, CSA plus recombinant human granulocyte-macrophage colony
      stimulating factor (rhuGM-CSF) and rhu erythropoietin (rhuEPO) (IST regimen III);
      or rabbit ATG (ATG-F), CSA, rhuGM-CSF, and rhuEPO (IST regimen IV). No repeated
      courses of E-ATG or ATG-F were given for nonresponders. All patients also
      received stanozolol or testosteron propionate. RESULTS: The overall response rate
      to IST regimen I was 58%. The response to IST regimen II (79%) was significantly
      higher (p = 0.04), more rapid and complete than after IST regimen I. The response
      rate to IST regimen IV (53%) was significantly lower than that of IST regimen III
      (73%, p = 0.039). The additional use of growth factors did not reduce early
      deaths and did not accelerate hematopoietic recovery after IST. Of the 142
      patients enrolled in this trial, 92 (65%) are alive at a median follow-up time of
      102 months (range, 54-166 months). The 5-year actuarial survival for IST regimens
      I, II, III, and IV was 58%, 81%, 80%, and 66%, respectively. CONCLUSION: The
      combination of E-ATG and CSA remains the best combination for the treatment of
      SAA patients, producing a survival advantage at 5 years. The addition of growth
      factors did not improve these results. Rabbit ATG-F appeared less effective than
      E-ATG.

PMID- 16797410
TI  - Evaluation of CD34+ - and Lin- -selected cells from peripheral blood stem cell
      grafts of patients with lymphoma during differentiation in culture ex vivo using
      a cDNA microarray technique.
AB  - OBJECTIVE: Hematopoietic stem cells (enriched in fraction of CD34+ cells) have
      the ability to regenerate hematopoiesis in all of its lineages, and this
      potential is clinically used in transplanting bone marrow or peripheral blood
      stem cells. Our objective was to assemble a suitable method for evaluating gene
      expression in enriched populations of hematopoietic stem cells. We compared
      biologic properties of cells cultured ex vivo obtained using two different ways
      of immunomagnetic separation (positive selection of CD34+ cells and negative
      selection of Lin- cells) by means of a cDNA microarray technique. METHODS: CD34+
      and Lin- cells were enriched from peripheral blood stem cell (PBSCs) grafts of
      patients with non-Hodgkin's lymphoma. Isolated cells were in the presence of
      cytokine PBSCs, Flt-3 ligand, interleukin-3, interleukin-6, and granulocyte
      colony-stimulating factor. At days 0, 4, 6, 8, 10, 12, and 14 cells were
      harvested and analyzed by cDNA microarrays. Total cell expansion, CD34+, colony
      forming unit for granulocyte-macrophage and megakaryocytes expansion, vitality,
      and phenotype of cells were also analyzed. RESULTS: cDNA microarray analysis of
      cultured hematopoietic cells proved equivalence of the two enrichment methods for
      PBSC samples and helped us characterize differentiating cells cultured ex vivo.
      CONCLUSION: Our methodologic approach is helpful in characterizing cultured
      hematopoietic cells cultured ex vivo, but it is also suitable for more general
      purposes. Equivalence of CD34+ and Lin- selection methods from PBSC samples
      proved by cDNA microarray may have an implication for graft manipulation in an
      experimental setting of hematopoietic transplantation. Total cell expansion and
      colony formation and phenotype from CD34+ selected and from Lin- samples were
      comparable.

PMID- 16797411
TI  - Recombinant human erythropoietin therapy after allogeneic hematopoietic cell
      transplantation with a nonmyeloablative conditioning regimen: low donor chimerism
      predicts for poor response.
AB  - PURPOSE: After allogeneic hematopoietic stem cell transplantation with
      nonmyeloablative conditioning (NMHCT), many patients experience prolonged anemia
      and require red blood cell (RBC) transfusions. We enrolled 60 consecutive
      patients undergoing NMHCT in a phase II trial to determine the optimal
      utilization of recombinant human erythropoietin (rHuEPO) therapy in this setting.
      PATIENTS AND METHODS: The first 14 NMHCT recipients did not receive rHuEPO
      (control group). Nineteen patients were scheduled to start rHuEPO on day 0 (EPO
      group 2) and 27 patients on day 28 after the transplant (EPO group 1). RHuEPO was
      administered subcutaneously once weekly at a dose of 500 U/kg/wk with the aim of
      achieving hemoglobin (Hb) levels of 13 g/dL. The 3 groups were well balanced for
      major characteristics. RESULTS: During the first month (p < 0.0001) as well as
      days 30 to 100 (p < 0.0001) and days 100 to 180 (p < 0.0001), Hb values were
      higher in patients receiving rHuEPO compared to those not receiving it. However,
      transfusion requirements were significantly decreased only in the first month in
      EPO group 2 (p = 0.0169). T-cell chimerism above 60% on day 42 was the best
      predictor of Hb response (p < 0.0001) or Hb correction (p = 0.0217), but myeloid
      chimerism above 90% also predicted for Hb response (p = 0.0069). Hb response was
      also decreased in patients receiving CD8-depleted grafts and increased in the few
      patients not receiving TBI, but only in univariate analysis. CONCLUSIONS: Anemia
      after NMHCT is sensitive to rHuEPO therapy, but less so than after conventional
      allogeneic HCT. RHuEPO decreases transfusion requirements only in the first 30
      days posttransplant. T-cell chimerism below 60% on day 42 impaired Hb response,
      suggesting possible inhibition of donor erythropoiesis by residual recipient
      lymphocytes. A prospective randomized trial should be performed with rHuEPO
      starting on the day of transplantation to assess its clinical benefit in terms of
      transfusion requirements and quality of life.

PMID- 16797412
TI  - Interleukin-7 partially rescues B-lymphopoiesis in osteopetrotic oc/oc mice
      through the engagement of B220+ CD11b+ progenitors.
AB  - OBJECTIVE: We recently identified in the mouse bone marrow a B-lymphoid/myeloid
      B220+ CD11b+ progenitor population. This population is accumulated in the
      osteopetrotic oc/oc mouse, which suggests that it could be controlled by bone
      marrow factors whose expression varies in this pathologic bone environment. Among
      the possible factors, interleukin (IL)-7 is involved in the control of B
      lymphopoiesis and osteoclastogenesis. Therefore, we hypothesized that IL-7 could
      regulate the accumulation of the B220+ CD11b+ population in oc/oc mice. METHODS:
      B220+ CD11b+ cells sorted from oc/oc mice were treated with IL-7 and their
      phenotype was analyzed by flow cytometry and real-time reverse transcriptase
      polymerase chain reaction (RT-PCR). In vivo, IL-7 was injected in oc/oc mice, and
      B220+ CD11b+ and B cells, as well as B-cell proliferation and apoptosis, were
      analyzed by flow cytometry. The expression of B lymphopoiesis and myelopoiesis
      markers was analyzed by real-time RT-PCR. RESULTS: In vitro, IL-7 induced the
      differentiation of B220+ CD11b+ cells into B lymphocytes through the induction of
      Pax5 and the inhibition of myeloid markers. In vivo, IL-7 injections in oc/oc
      mice induced a decrease of the B220+ CD11b+ population and the partial
      restoration of B-cell population, which was reduced in oc/oc mice. In parallel,
      upon IL-7 injections, Pax5 expression was induced in B220+ cells and B-cell
      apoptosis was reduced. CONCLUSIONS: Our results demonstrate that IL-7 injection
      can partially rescue B lymphopoiesis in oc/oc mice through the engagement of the
      B220+ CD11b+ population in the B-lymphoid pathway. Therefore, IL-7 delivery could
      represent a new therapeutic perspective to circumvent the lymphopenia observed in
      infantile malignant osteopetrosis patients.

PMID- 16797413
TI  - Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic
      leukemia (B-CLL) recognized by autologous CD8+ T cells.
AB  - OBJECTIVE: CD229, a cell-surface molecule being involved in cell adhesion, is
      overexpressed in B-CLL cells. In this study we wanted to explore whether CD229
      might function as B-CLL-specific tumor-associated antigen (TAA). PATIENTS AND
      METHODS: Autologous, CD229-specific HLA-A2-restricted T cells were identified
      using IFN-gamma-ELISPOT assays and HLA-A2/dimer-peptide staining after 4 weeks of
      in vitro culture. RESULTS: We were able to expand autologous T cells from 9/11 B
      CLL patients using native B-CLL cells as antigen presenting cells (APCs) in 5
      cases, whereas for 4 samples an autologous T-cell response could only be evoked
      by use of CD40L-stimulated B-CLL cells as APCs. The number of CD8+ T cells could
      be expanded during 4 weeks of in vitro culture with native or CD40L-activated B
      CLL cells while the amount of specific T cells recognizing CD229 peptides bound
      to HLA-A2 dimers increased on average 12-fold (native CLL) and 13-fold (CD40L
      activated CLL), respectively. Using IFN-gamma-ELISPOT assays we could demonstrate
      that the expanded T cells were able to secrete IFN-gamma upon recognition of the
      antigen. These T cells not only recognized HLA-A0201-binding CD229-derived
      peptides presented by T2 cells, but also CD229-overexpressing autologous B-CLL
      cells in an MHC-I-restricted manner. CONCLUSION: In summary, CD229 was shown to
      be naturally processed and presented as TAA in primary B-CLL cells, enabling the
      expansion of autologous tumor-specific T cells.

PMID- 16797414
TI  - Canine hemangiosarcoma originates from hematopoietic precursors with potential
      for endothelial differentiation.
AB  - OBJECTIVE: Two competing hypotheses can be formulated regarding the origin of
      canine hemangiosarcoma (HSA). One states HSA originates from differentiated
      vascular endothelial cells that undergo mutations which endow them with malignant
      potential. The other states HSA originates from transformed hemangioblastic stem
      cells. This study was designed to begin to distinguish between these
      possibilities, as well as to test if flow cytometry was sufficiently sensitive to
      detect malignant cells in blood samples from dogs with HSA. METHODS: We used
      multiparameter flow cytometry to examine expression of cell-surface determinants
      associated with hematopoietic precursors (c-kit, CD34, CD133, CD45) or with
      lineage-committed cells (CD3, CD11b, CD14, CD21, CD105, CD146, alphavbeta3
      integrin) in HSA cell lines and in blood samples from healthy dogs or dogs with
      HSA. RESULTS: The data show that HSA cells coexpress surface markers associated
      with hematopoietic precursors and with commitment to endothelial lineage,
      providing a means to identify their presence in circulation and distinguish them
      from normal or malignant white blood cells. The percentage of cells that
      coexpressed these markers ranged from 0.5 to 1.25% for HSA dogs, and was less
      than 0.3% for unaffected dogs or dogs with HSA that had the tumors removed within
      48 hours prior to obtaining samples. CONCLUSIONS: The results place the ontogeny
      of HSA with multipotential bone marrow-derived stem cells whose progeny arrest
      differentiation at the hemangioblast or angioblast stage. In addition, these
      expression patterns may assist to confirm an HSA diagnosis, monitor minimal
      residual disease, and detect the disease in early stages.

PMID- 16797415
TI  - Dendritic cells of immune thrombocytopenic purpura (ITP) show increased capacity
      to present apoptotic platelets to T lymphocytes.
AB  - OBJECTIVE: Altered self-antigen processing/presentation of apoptotic cells by DCs
      and/or modifications of autoantigens may lead to the development of
      autoantibodies. Increasing evidence indicates that platelets may undergo
      apoptosis. Therefore, in the present study we investigated whether platelet
      apoptosis and/or dendritic cells (DCs) may play a role in the stimulation of the
      immuno-mediated anti-platelet response in chronic immune thrombocytopenic purpura
      (ITP). METHODS AND RESULTS: Twenty-nine patients with active ITP and 29 healthy
      adult volunteers were enrolled into the study. Freshly washed platelets and
      platelets aged in a plasma-free buffer for 72 hours at 37 degrees C were assessed
      by flow cytometry for phosphatidylserine exposure using annexin V-FITC, caspase
      activation, and platelet activation markers. CD14-derived DCs were characterized
      by immunophenotyping, cytokine production, and ability to present fresh and aged
      platelets to T lymphocytes. We demonstrated that platelets from ITP patients,
      either fresh or in vitro aged, show increased apoptosis (with low levels of
      activation) in comparison to their normal counterparts. We also found that
      immature DCs readily ingest apoptotic platelets. Furthermore, in ITP patients
      DCs, prepulsed with autologous/allogeneic fresh and aged platelets, are highly
      efficient in stimulating autologous T-cell proliferation as compared to DCs
      derived from healthy donors. This finding may be related to the upregulated
      expression of CD86 in DCs from ITP patients and not to higher phagocytic
      activity. CONCLUSION: These results suggest that DC dysfunction, together with
      increased propensity of platelets to undergo apoptosis, may play a role in the
      stimulation of the immune system in ITP.

PMID- 16797416
TI  - The role of leukemia-derived B7-H1 (PD-L1) in tumor-T-cell interactions in
      humans.
AB  - OBJECTIVE: Expression of the B7 homolog B7-H1 (PD1-Ligand) has been proposed to
      enable tumor cells to evade immune surveillance. Recently, B7-H1 on murine
      leukemia cells was reported to mediate resistance to cytolytic T-cell
      destruction. We here investigate the expression and function of the B7 homolog B7
      H1 in human leukemia. PATIENTS AND METHODS: Leukemia cells from 30 patients and 9
      human leukemia cell lines were investigated for B7-H1 expression by flow
      cytometry. Functional relevance of B7-H1 for tumor-immune interactions was
      assessed by coculture experiments using purified, alloreactive CD4 and CD8 T
      cells in the presence of a neutralizing anti-B7-H1 antibody. RESULTS: Significant
      B7-H1 expression levels on leukemia cells were detected in 17 of 30 patients and
      in eight of nine cell lines. In contrast to various other tumor entities and the
      data reported from a murine leukemia system, no significant inhibitory effect of
      leukemia-derived B7-H1 on CD4 and CD8 cytokine production (IFN-gamma, IL-2),
      proliferation or expression of T-cell activation markers (ICOS, CD69) was
      observed. Furthermore, in the presence of neutralizing B7-H1 antibody (mAb 5H1)
      occurred no significant changes in T cell IFN-gamma or IL-2 production or
      proliferation. CONCLUSIONS: Our data demonstrate that leukemia-derived B7-H1
      seems to have no direct influence on T-cell activation, proliferation, and
      cytokine production in humans. Further experiments are warranted to delineate
      factors and characterize yet-unidentified B7-H1 receptor(s) that determine
      inhibitory and stimulatory functions of B7-H1 in human leukemia.

PMID- 16797417
TI  - Graft engineering using ex vivo methods to limit GVHD: fludarabine treatment
      generates superior GVL effects in allogeneic BMT.
AB  - OBJECTIVE: To compare the abilities of different ex vivo methods of treating
      donor lymphocytes to inhibit graft-vs-host disease (GVHD) while preserving graft
      vs-leukemia (GVL) activity in murine models of allogeneic bone marrow
      transplantation. METHODS: Donor/recipient pairs included MHC fully mismatched,
      MHC haplomismatched, and MiHA mismatched strain combinations. T cell-depleted BM
      (TCD-BM) was transplanted in combination with untreated, fludarabine-treated, 7.5
      Gy gamma-irradiated, or psoralen/UVA (PUVA)-treated splenocytes. GVL activity was
      studied by adding a lethal number of recipient-type lymphoma cells.
      Posttransplant survival was determined, and GVHD and GVL activity were assessed
      by clinical and pathological scoring. Hematopoietic chimerism and donor T-cell
      expansion were analyzed by flow cytometry of peripheral blood samples at 30 and
      60 days posttransplant. RESULTS: Allogeneic splenocytes treated with fludarabine,
      7.5 Gy gamma-irradiation, or PUVA had significantly diminished GVHD activity, and
      all treated donor T cells facilitated engraftment by low-dose TCD-BM. Allogeneic
      splenocytes treated with fludarabine and, to a lesser extent, PUVA retained GVL
      activity and contributed more to donor T-cell chimerism compared to gamma
      irradiated donor splenocytes. CONCLUSION: Among ex vivo methods of treating donor
      T cells to limit their proliferative capacity, fludarabine exposure had the
      greatest differential ability to inhibit the GVHD activity of allogeneic
      lymphocytes, while preserving their GVL activity and ability to engraft
      recipients. Thus, ex vivo treatment with fludarabine was superior to gamma
      irradiation or PUVA in separating GVL from GVHD activity in murine models of
      allogeneic bone marrow transplantation.

PMID- 16797418
TI  - Anti-bovine CD34 monoclonal antibody reveals polymorphisms within coding region
      of the CD34 gene.
AB  - OBJECTIVE: Monoclonal antibodies (mAbs) against CD34 are widely used for
      purification of CD34+ hematopoietic as well as nonhematopoietic stem/progenitor
      cells. We produced mAbs against bovine CD34 (boCD34) to facilitate the study of
      hematopoiesis in cattle. METHODS: MAbs were produced by immunizing BALB/c mice
      with BALB/3T3 cells transfected with boCD34 cDNA. Staining of bone marrow
      mononuclear cells (BMMNCs) from 10 newborn Holstein calves with the mAbs was
      examined by flow cytometry. The nucleotide sequence of the coding region for
      boCD34 in each calf was determined after amplification of the cDNA by reverse
      transcription polymerase chain reaction (RT-PCR). BoCD34 fusion proteins, each
      representing one of the boCD34 alleles found to exist in the calves, were
      expressed in HeLa cells by DNA transfection, and the staining of these proteins
      with the mAbs was assessed. RESULTS: One mAb, N21, stained relatively high
      percentages of BMMNCs from 4 calves but failed to stain those from the other
      calves. RT-PCR analysis revealed single-nucleotide polymorphisms within the
      coding region, 3 of which led to amino-acid substitutions. A CD34 mutation
      experiment indicated that mAb N21 bound to a boCD34 allele with tryptophan at
      amino acid 167 but not to that with arginine. CONCLUSION: By using mAb N21 as an
      allelic cell marker, it would be feasible to detect and isolate boCD34+ cell
      species derived from N21+ donors in N21- recipients following allogeneic in utero
      transplantation; this would make cattle potentially useful as large animal models
      with a unique experimental advantage.

PMID- 16797419
TI  - Early appearance of stem/progenitor cells with neural-like characteristics in
      human cord blood mononuclear fraction cultured in vitro.
AB  - OBJECTIVE: The exposure of human umbilical cord blood mononuclear cells devoid of
      hematopoietic stem cells (HUCB-MNCsCD34-) to defined culture condition promotes
      their conversion into neural lineage. We have asked the question if observed fate
      change of HUCB-MNCsCD34- results from direct conversion of hematopoietic
      precursors into neural-like phenotypes due to expression of overlapping genetic
      program or, alternatively, these neural phenotypes arise from sequential
      differentiation of more primitive progenitors (embryonic-like cells) preexisting
      in HUCB-MNCsCD34- fraction. MATERIALS AND METHODS: HUCB-MNCs negatively selected
      for CD34 antigens were cultured in vitro up to 14 days. Changes in stem/neural
      cell genes and proteins were successively evaluated during this period and after
      evoked neuronal differentiation of cells in the presence of RA or BDNF or
      cocultured with neonatal rat brain astrocytes. RESULTS: Freshly isolated HUCB
      MNCsCD34- expressed pluripotent cell markers: Oct3/4, Sox2, and Rex1 genes.
      During 24 hours of culture the frequency of Oct3/4 immunopositive cells increased
      markedly with parallel enlargement of "side population" and CD133+ cell
      appearance. Concomitantly, cultured cells start to form aggregates and express
      pro-neural genes, i.e., enhanced Sox2, OTX1, Nestin, GFAP, and NF-200. During the
      next days of culture immunoreactions for beta-tubulin III, MAP2, GFAP, S100beta,
      Doublecortin, and GalC were induced with reciprocal lowering of stem cell gene
      and protein markers. At this stage cells successively adhered to the bottom,
      dispersed, and decreased proliferation rate (Ki67 expression). Additional
      treatments with neuromorphogenes or coculturing with rat brain primary culture
      induced further differentiation of these neural precursors toward more advanced
      neuronal phenotypes. CONCLUSIONS: HUCB-MNCs(CD34-) fraction contains embryonic
      like stem/progenitor cells which increase rapidly but transiently in culture,
      then differentiate spontaneously after cell aggregate adhesion toward neural
      lineage. Neurally promoted cells from 10-14 DIV culture acquire three main neural
      like phenotypes, i.e., neurons, astrocytes, and oligodendrocytes. In this respect
      they are promising candidates for experimental treatment of neuronal injury;
      however, the final proof for conversion of HUCB cells to neural cells can be
      obtained through transplantation experiments.

PMID- 16797420
TI  - The time course of engraftment of human mesenchymal stem cells in fetal heart
      demonstrates that Purkinje fiber aggregates derive from a single cell and not
      multi-cell homing.
AB  - OBJECTIVE: To study the early time course of engraftment of human mesenchymal
      stem cells in fetal sheep heart and determine the relative roles of proliferation
      and homing in formation of aggregates of human Purkinje fiber cells. METHODS: The
      human sheep xenograft model was utilized for these studies. Prior to injection in
      the preimmune fetus, human cells were labeled with fluorescent dyes to be able to
      track human cells at early times of engraftment. RESULTS: Human stem cells were
      detected in fetal hearts between 29 and 39 hours after intraperitoneal injection.
      Engraftment was primarily in the Purkinje fiber system. By 45 hours engrafted
      human cells had a cardiac phenotype. When two groups of human mesenchymal stem
      cells, each labeled with a different fluorescent dye, were combined prior to
      injection, aggregates of human Purkinje fiber cells contained cells labeled with
      either one dye or the other, no aggregate contained cells labeled with both dyes.
      CONCLUSIONS: Human mesenchymal stem cells introduced into fetal sheep rapidly
      enter the myocardium. The swift differentiation into a cardiac phenotype
      indicates that the cardiac milieu has a strong influence on the fate of
      engrafting human mesenchymal stem cells. The absence of any aggregates of human
      Purkinje fiber cells containing both fluorescent dyes demonstrates that each
      aggregate of human Purkinje fiber cells is derived from a single mesenchymal stem
      cell and not from homing of multiple cells to a hotspot.

PMID- 16797421
TI  - Donor multipotent mesenchymal stromal cells may engraft in pediatric patients
      given either cord blood or bone marrow transplantation.
AB  - OBJECTIVE: Multipotent mesenchymal stromal cells (MSCs) are endowed with
      multilineage differentiative potential and immunomodulatory properties. It is
      still a matter of debate whether donor MSCs have sustained engraftment potential
      in host bone marrow (BM) after allogeneic hematopoietic stem cell transplantation
      (allo-HSCT). The aim of this study was to analyze the donor/recipient origin of
      MSCs in children receiving allogeneic either BM or cord blood (CB)
      transplantation. METHODS: Thirty-seven pediatric patients undergoing allo-HSCT
      for either a malignant or a nonmalignant disorder were enrolled in the study; 19
      received CB and 18 BM transplantation. Results were compared with those obtained
      in 14 adults given BM transplantation for either malignant or nonmalignant
      disorders. MSCs were grown from BM aspirates obtained 1-17 and 2-192 months after
      allo-HSCT in pediatric and adult patients, respectively. MSC samples at the third
      fourth passage were phenotypically characterized. Donor/recipient origin of MSCs
      was assessed by amelogenin assay and microsatellite analysis. RESULTS: MSCs could
      be grown from 30 of 37 children; at the third-fourth passage MSCs resulted
      positive (> or = 98%) for CD73, CD105, CD106, CD29, CD13, CD44 and negative (< or
      = 1%) for CD34, CD45, CD14. Mixed chimerism with donor cells was observed in 4 BM
      and 5 CB transplantation recipients, respectively; full recipient chimerism was
      detected in the remaining children. Full recipient MSC chimerism was observed
      also in all assessable (12/14) adult patients. CONCLUSIONS: BM of pediatric
      patients might be a more favorable milieu than that of adults for sustained
      engraftment of transplanted MSCs. MSCs able to engraft in the host can be
      transferred with cryopreserved CB units.

PMID- 16797422
TI  - Ex vivo culture of human CD34+ cord blood cells with thrombopoietin (TPO)
      accelerates platelet engraftment in a NOD/SCID mouse model.
AB  - OBJECTIVES: Hematopoietic recovery, in particular platelet reconstitution, can be
      severely delayed after transplantation with cord blood (CB) stem cells (SC).
      Expansion of CB SC may be one way to improve the recovery, but there is concern
      that ex vivo expansion compromises the repopulating ability of SC. METHODS: We
      used a short-term expansion protocol with TPO as single growth factor. The
      expanded cells were tested in the NOD/SCID mouse model and both platelet recovery
      and repopulation capacity were examined and compared with unexpanded CD34+ CB
      cells of the same CB donor. RESULTS: Platelet recovery started 1 week earlier in
      mice transplanted with TPO-expanded CD34+ cells and at days 5 and 8 after
      transplantation, 6.2 +/- 2.6 and 13.9 +/- 6.7 plt/microL were observed,
      respectively. At similar time intervals 0.0 and 1.5 +/- 0.2 plt/microL
      respectively were detected in mice receiving the unmanipulated CD34+ grafts. This
      was accompanied by a higher number of CFU-Mk in the bone marrow (BM) 7 days after
      transplantation. Moreover, the BM engraftment and the lineage differentiation of
      human cells at 6 weeks after transplantation was similar, suggesting that long
      term engraftment was not compromised by the expansion procedure. CONCLUSION: Ex
      vivo expansion with TPO as single growth factor results in an accelerated
      platelet recovery in NOD/SCID mice and appears not to affect the long-term
      repopulation capacity.

PMID- 16797423
TI  - Rapid immune reconstitution and dendritic cell engraftment post-bone marrow
      transplantation with heterogeneous progenitors and GM-CSF treatment.
AB  - OBJECTIVE: Bone marrow/hematopoietic stem cell transplantation (BMT) has been the
      treatment of choice for severe hematological diseases and cancers. Rapid host
      immune recovery following BMT is critical for reducing complications and
      improving therapeutic outcome. Here we report manipulations that facilitate rapid
      immune and dendritic cell (DC) reconstitution post-BMT for improvement in
      therapeutic outcome of BMT-based disease treatment. METHODS: Using lentiviral
      vector-modified or unmodified murine hematopoietic stem cells, we examined the
      engraftment efficiency and kinetics in immune reconstitution of unfractionated
      bone marrow cells (BM), lineage marker-negative (Lin-) hematopoietic progenitor
      cells (HPC), or purified Lin-Sca-1+ hematopoietic stem cells (HSC) at an equal
      hematopoietic progenitor number. RESULTS: Our study revealed that BM
      reconstituted host primary and secondary lymphoid tissues more efficiently and
      rapidly. Moreover, in a competitive BMT setting using lentiviral vector
      engineered BM and HSC expressing GFP or DsRed respectively, we showed that GM-CSF
      treatment further enhanced DC reconstitution to therapeutic relevant level as
      early as 2 weeks post-BMT. On the other hand, Flt3 ligand was less effective in
      enhancing DC reconstitution till 3 weeks post-BMT. This accelerated DC
      engraftment by GM-CSF treatment correlated well with improved overall immune
      reconstitution and enhanced activation of antigen-specific T cells post-BMT.
      CONCLUSION: This study suggests that use of heterogeneous BM for transplantation
      facilitates more rapid immune reconstitution, especially in the presence of DC
      stimulating cytokines. This improved immune reconstitution would provide
      additional therapeutic benefits for BMT-based immunotherapy and gene therapy of
      genetic disorders and cancers.

PMID- 16797424
TI  - Comparison of hemodynamic profiles in transurethral resection of prostate vs
      transurethral resection of urinary bladder tumors during spinal anesthesia: a
      bioimpedance study.
AB  - STUDY OBJECTIVE: Transurethral resection of prostate (TURP) is more frequently
      associated with perioperative fluid and electrolyte disturbances than
      transurethral resection of bladder tumors (TURT) because of irrigating fluid
      absorption. Because fluid overload may cause hypertension, we compared the
      patients' intraoperative hemodynamic profiles (including the incidence of
      hypertension) during TURP vs TURT, both performed during spinal anesthesia, by
      using the bioimpedance method. DESIGN: Prospective single-blind study. SETTING:
      University hospital. PATIENTS: 80 (40 in each group) men, ASA physical status I
      and II. INTERVENTIONS: Patients underwent TURP or TURT surgery with spinal
      anesthesia. MEASUREMENTS: Mean arterial pressure, heart rate, cardiac index, and
      systemic vascular resistance were compared between the 2 groups. A mean arterial
      pressure greater than 30% from the baseline value was considered as hypertension.
      Plasma sodium was measured preoperatively, intraoperatively, and postoperatively.
      MAIN RESULTS: Transurethral resection of prostate patients received more
      irrigating fluid (7900 +/- 2310 vs 5650 +/- 21560, P < 0.05) and had a higher
      calculated volume of fluid absorbed: 638 +/- 60 vs 303 +/- 40 mL for the TURT
      patients (P < 0.05). Mean arterial pressures were higher with TURP, 30 minutes
      after the onset of surgery and at the end of the procedure (111 +/- 15 vs 100 +/-
      10 and 109 +/- 14 vs 99 +/- 14 mmHg, respectively; P < 0.05). However, there was
      no hypertension in either group. There were no differences in hemodynamic
      measurements of hyponatremic vs normonatremic patients. Plasma sodium decreased
      postoperatively more in the TURP group (140.4 +/- 2.6 mEq/L baseline to 134.1 +/-
      3.5 mEq/L, P < 0.05) and was lower postoperatively in the TURP group compared
      with TURT (134.1 +/- 3.5 vs 137.2 +/- 2.9 mEq/L, P = 0.04). CONCLUSIONS: Although
      more irrigating fluid was absorbed in the TURP group, there were no episodes of
      hypertension in either group.

PMID- 16797425
TI  - Peripheral venous pressure as a predictor of central venous pressure during
      orthotopic liver transplantation.
AB  - STUDY OBJECTIVE: To assess the reliability of peripheral venous pressure (PVP) as
      a predictor of central venous pressure (CVP) in the setting of rapidly
      fluctuating hemodynamics during orthotopic liver transplant surgery. DESIGN:
      Prospective clinical trial. SETTING: UCLA Medical Center, main operating room
      liver transplant surgery. PATIENTS: Nine adult patients with liver failure
      undergoing orthotopic liver transplant surgery. INTERVENTIONS: A pulmonary artery
      catheter and a 20-g antecubital peripheral intravenous catheter dedicated to
      measuring PVP were placed in all patients after standard general endotracheal
      anesthesia induction and institution of mechanical ventilation. MEASUREMENTS:
      Peripheral venous pressure and CVP were recorded every 5 minutes and/or during
      predetermined, well-defined surgical events (skin incision, venovenous bypass
      initiation, portal vein anastamosis, 5 minute post graft reperfusion, abdominal
      closure). Pulmonary artery pressure and cardiac output (via thermodilution) were
      recorded every 15 and 30 minutes, respectively. MAIN RESULTS: Peripheral venous
      pressure (mean +/- SD) was 11.0 +/- 4.5 mmHg vs a CVP of 9.5 +/- 5.0; the two
      measurements differed by an average of 1.5 +/- 1.6 mmHg. Peripheral venous
      pressure correlated highly with CVP in every patient, and the overall correlation
      among all nine patients calculated using a random-effects regression model was r
      = 0.95 (P < 0.0001). A Bland-Altman analysis used to determine the accuracy of
      PVP in comparison to CVP yielded a bias of -1.5 mmHg and a precision of +/-3.1 mm
      Hg. CONCLUSION: Our study confirms that PVP correlates with CVP even under
      adverse hemodynamic conditions in patients undergoing liver transplantation.

PMID- 16797426
TI  - Performance and customization of 4 prognostic models for postoperative onset of
      nausea and vomiting in ear, nose, and throat surgery.
AB  - OBJECTIVE: To evaluate the performance of 4 published prognostic models for
      postoperative onset of nausea and vomiting (PONV) by means of discrimination and
      calibration and the possible impact of customization on these models. DESIGN:
      Prospective, observational study. SETTING: Tertiary care university hospital.
      PATIENTS: 748 adult patients (>18 years old) enrolled in this study. Severe
      obesity (weight > 150 kg or body mass index > 40 kg/m) was an exclusion
      criterion. INTERVENTIONS: All perioperative data were recorded with an anesthesia
      information management system. A standardized patient interview was performed on
      the postoperative morning and afternoon. MEASUREMENTS: Individual PONV risk was
      calculated using 4 original regression equations by Koivuranta et al, Apfel et
      al, Sinclair et al, and Junger et al Discrimination was assessed using receiver
      operating characteristic (ROC) curves. Calibration was tested using Hosmer
      Lemeshow goodness-of-fit statistics. New predictive equations for the 4 models
      were derived by means of logistic regression (customization). The prognostic
      performance of the customized models was validated using the "leaving-one-out"
      technique. MAIN RESULTS: Postoperative onset of nausea and vomiting was observed
      in 11.2% of the specialized patient population. Discrimination could be
      demonstrated as shown by areas under the receiver operating characteristic curve
      of 0.62 for the Koivuranta et al model, 0.63 for the Apfel et al model, 0.70 for
      the Sinclair et al model, and 0.70 for the Junger et al model. Calibration was
      poor for all 4 original models, indicated by a P value lower than 0.01 in the C
      and H statistics. Customization improved the accuracy of the prediction for all 4
      models. However, the simplified risk scores of the Koivuranta et al model and the
      Apfel et al model did not show the same efficiency as those of the Sinclair et al
      model and the Junger et al model. This is possibly a result of having relatively
      few patients at high risk for PONV in combination with an information loss caused
      by too few dichotomous variables in the simplified scores. CONCLUSIONS: The
      original models were not well validated in our study. An antiemetic therapy based
      on the results of these scores seems therefore unsatisfactory. Customization
      improved the accuracy of the prediction in our specialized patient population,
      more so for the Sinclair et al model and the Junger et al model than for the
      Koivuranta et al model and the Apfel et al model.

PMID- 16797427
TI  - A comparison of anesthesiology resident and faculty electronic evaluations before
      and after implementation of automated electronic reminders.
AB  - STUDY OBJECTIVE: To develop an automated e-mail reminder system to contact
      residents and faculty regarding incomplete evaluations. DESIGN, SETTING,
      INTERVENTION, AND MEASUREMENTS: In the retrospective study, two 9-month periods
      were evaluated representing pre- and post-introduction of the automated e-mail
      reminder system. Data collected contained the number of evaluations completed and
      the rating of residents and faculty at the University of Michigan Health System
      in 5 different categories on a 5-point scale. MAIN RESULTS: The use of electronic
      reminders resulted in a nearly 4-fold increase in the number of resident
      evaluations by faculty from 1050 to 3761. Faculty completing evaluations
      increased from 40 (61%) to 66 (100%). The mean evaluation scores showed
      statistically significant but clinically negligible change for resident
      judgement, interpersonal skills, and intraoperative management. Resident
      preoperative evaluation and knowledge did not show statistically significant
      changes. Residents completing evaluations of faculty increased from 244 to 1798,
      and the number of residents completing evaluations rose from 40 (56%) to 87
      (100%). There were no statistically significant changes in the evaluation of
      faculty except in the category of feedback. CONCLUSION: An automated e-mail
      reminder system implemented to contact residents and faculty regarding incomplete
      evaluations for residents and faculty dramatically enhanced participation in the
      evaluation process.

PMID- 16797428
TI  - Anesthesia and pain management for pediatric patients with dystrophic
      epidermolysis bullosa.
AB  - STUDY OBJECTIVE: To review anesthesia and pain management in pediatric patients
      with recessive dystrophic epidermolysis bullosa (RDEB). STUDY DESIGN:
      Retrospective study. SETTING: University-affiliated pediatric hospital. PATIENTS:
      25 pediatric patients with RDEB had a total of 121 surgical procedures.
      MEASUREMENTS AND MAIN RESULTS: Pediatric patients with RDEB could have vesicles
      and bullae formation in the skin in response to trauma, friction, or pressure.
      The common surgical procedures for patients with RDEB were balloon dilation of
      esophageal strictures (38%), pseudosyndactyly release with or without skin graft
      (27%), postsurgical or skin care related dressing changes (21%), percutaneous
      endoscopic gastrostomy tube placement (8%), and circumcision (2%). Our anesthetic
      techniques included general inhalational anesthesia using mask (21%), general
      anesthesia using endotracheal tube (48%), and intravenous sedation (31%). No
      death or other major perioperative anesthetic complications occurred in these
      reported cases. CONCLUSIONS: Patients with RDEB can present considerable
      management issues for the anesthesiologists. Anesthesia and pain management can
      be carefully delivered with proper preoperative evaluation and preparation for
      pediatric patients with RDEB.

PMID- 16797429
TI  - Similar recovery from bispectral index-titrated isoflurane and sevoflurane
      anesthesia after outpatient gynecological surgery.
AB  - STUDY OBJECTIVE: To test the hypothesis that the recovery of gynecological day
      case patients is equally fast after isoflurane and sevoflurane anesthesia, when
      administration of the inhaled agent is adjusted by monitoring the bispectral
      index (BIS). DESIGN: Prospective, randomized, controlled, single-blinded clinical
      study. SETTING: University-affiliated women's hospital. PATIENTS: 120 adult
      female patients, ASA physical status I or II, scheduled for ambulatory surgery
      under general anesthesia. INTERVENTIONS: Patients were randomized to receive
      either isoflurane or sevoflurane as the maintenance anesthetic. BIS values were
      titrated to remain between 50 and 60 during the maintenance of anesthesia by
      adjusting the inspired concentration of the inhaled agent. Administration of the
      inhaled agent was discontinued abruptly at the end of the procedure.
      MEASUREMENTS: The times to achieving several recovery end points were recorded.
      The main outcome parameter was the time to home-readiness. In the postoperative
      care unit, sedation was evaluated with the digit-symbol substitution test. The
      degree of pain and nausea was evaluated on the visual analog scale. MAIN RESULTS:
      There were no statistically significant differences in the times to home
      readiness, or in any other parameters of early or intermediate recovery between
      the 2 groups. The degrees of sedation, pain, and nausea in the postoperative care
      unit were similar in the 2 groups. CONCLUSIONS: Isoflurane and sevoflurane are
      equally acceptable maintenance anesthetics in terms of the speed and quality of
      recovery in gynecological ambulatory surgery patients when the dose of the
      inhaled agent is adjusted to achieve a BIS between 50 and 60.

PMID- 16797430
TI  - Early increases in cardiac troponin levels after major vascular surgery is
      associated with an increased frequency of delayed cardiac complications.
AB  - OBJECTIVE: To evaluate changes in cardiac troponin-I levels after major vascular
      surgery and their association with early and late postoperative cardiac
      complications. DESIGN: Prospective, observational investigation. SETTING:
      University teaching hospital. PATIENTS: 75 consecutive patients undergoing major
      vascular surgery. INTERVENTIONS: All patients received a standard sevoflurane
      fentanyl anesthesia during the procedure. Blood levels of creatine kinase with MB
      subtype and cardiac troponin-I were assessed before surgery and then everyday for
      the first 3 days after surgery. At the same time, 12-lead electrocardiography was
      also performed, and occurrence of any cardiac adverse event was recorded.
      Patients were then followed up for 1 month after surgery. MEASUREMENT AND MAIN
      RESULTS: Troponin-I levels increased in 25 patients (33%) during the first 3 days
      after surgery; 9 of these patients (12%) had myocardial infarction. At univariate
      analysis, uncontrolled hypertension was the only risk factor for perioperative
      infarction (odds ratio, 16; (95% confidence interval, 3-74); however,
      multivariate logistic regression analysis failed to show statistically
      significant associations. Increases in troponin-I had a 100% sensitivity and 75%
      specificity in detecting myocardial ischemia with a 36% positive and 100%
      negative predictive values. Severe cardiac complication 1 month after surgery was
      reported in 5 patients (6.6%). The increase of cardiac troponin-I levels during
      the first 3 postoperative days was associated with an increased frequency of
      major cardiac complication at 1-month follow-up (P = 0.003), with a 100%
      sensitivity, 71% specificity, and 100% negative predictive value. CONCLUSIONS:
      Myocardial infarction after major noncardiac vascular surgery occurs in up to 12%
      of cases. Perioperative monitoring of troponin-I plasma levels may help to
      identify patients at increased risk for cardiac morbidity not only early after
      surgery but also during the first postoperative month.

PMID- 16797431
TI  - Thyrotoxic periodic paralysis and anesthesia report of a case and literature
      review.
AB  - Thyrotoxic periodic paralysis (TPP) is a disease characterized by recurrent
      episodes of paralysis and hypokalemia during a thyrotoxic state. The disease
      primarily affects people of Asian descent, but can affect other ethnic groups. In
      Asians, the symptoms of thyrotoxicosis are distinct and usually precede the first
      paralytic episode, whereas in non-Asian populations, paralysis is the presenting
      symptom. If TPP has not been diagnosed and the patient has a surgical procedure
      during general or regional anesthesia, symptoms of the disease may be confused
      with other adverse perioperative events such as delayed recovery from
      neuromuscular paralysis. No specific anesthetic regimen is superior. Current TTP
      treatment recommendations involve treating the underlying hyperthyroid state.
      Other modalities such as beta-blockade and potassium replacement are also
      important in the acute paralytic state. Future diagnostic and treatment
      innovations may lie in the genetic and molecular understanding of this disease.
      We present a case of an Asian male with known TPP undergoing general anesthesia,
      a brief case series involving 5 patients, and a review of the literature.

PMID- 16797432
TI  - Evidence of acute tolerance to remifentanil in intensive care but not in
      anesthesia.
AB  - We report the case of a 19-year-old man with a drug abuse history, admitted to
      the intensive care unit for head and chest trauma, who experienced an acute
      tolerance to sedative and respiratory depression effects of remifentanil, which
      was given as the sole agent for sedation. He did not exhibit any signs of drug
      tolerance or intraoperative awareness during prolonged remifentanil-based
      anesthesia using propofol or sevoflurane as adjuvants. Several recent studies
      support the hypothesis of a possible involvement of N-methyl-d-aspartate
      glutamate receptors. The clinical relevance of this report is that if a patient
      with a previously acute tolerance to remifentanil during sedation undergoes long
      term surgery, and propofol or sevoflurane is coadministered in a remifentanil
      based anesthesia, the patient will not necessarily develop opioid tolerance. It
      is of interest for anesthesiologists, given the high frequency of patients with
      drug abuse history who are admitted to intensive care units, often sedated with
      remifentanil, who undergo anesthesia for emergency surgery.

PMID- 16797433
TI  - The anesthetic management of a child with chronic hypotension for renal
      transplantation.
AB  - The anesthetic management of renal transplant recipients requires the maintenance
      of an adequate perfusion pressure to ensure viability of the donated kidney. A
      common finding among patients with end-stage renal disease is chronic
      hypertension. We report a case involving a 2-year-old child with an age-adjusted
      blood pressure below normal, undergoing transplantation of an adult cadaveric
      kidney, during which high-dose vasopressor medications were used to sustain the
      child's blood pressure at above-normal levels to help ensure perfusion of the
      adult allograft.

PMID- 16797434
TI  - Successful vaginal delivery for a parturient with complete aortic coarctation.
AB  - This report describes the case of a parturient with complete coarctation of the
      aorta that was diagnosed during pregnancy. The use of invasive monitoring and the
      choice of labor analgesia for vaginal delivery are reviewed. Management of
      patients with complex cardiac anomalies requires consultation among cardiologist,
      obstetricians, and anesthesiologists to ensure good outcome for the mother and
      baby.

PMID- 16797435
TI  - Prophylaxis of postoperative nausea and vomiting: controversies in the use of
      serotonin 5-hydroxytryptamine subtype 3 receptor antagonists.
AB  - Postoperative nausea and vomiting (PONV) continues to be a "big little problem"
      despite recent advances in anesthesia. Because of an increased interest in, and
      the abundant publications on this topic, guidelines for the management of PONV
      were published in 2003. Several key but controversial issues regarding PONV
      prophylaxis were left unaddressed, however. These included whether clinical
      differences exist between the 5-hydroxytryptamine subtype 3 (5-HT3) receptor
      antagonists, concern over optimal dosage and timing of administration, optimal 5
      HT3 receptor antagonist combination therapy, and whether rescue therapy is
      effective after prior administration of the same or a different 5-HT3 receptor
      antagonist. The application of these antiemetics in clinical practice has raised
      questions regarding the role of the 5-HT3 receptor antagonists in the treatment
      of postdischarge nausea and vomiting and opioid-induced nausea and vomiting. A
      brief overview of the incidence, risk factors and current management
      recommendations for PONV and current controversies with special emphasis on the 5
      HT3 receptor antagonists, is discussed.

PMID- 16797438
TI  - The development of children's understanding of death: cognitive and psychodynamic
      considerations.
AB  - The cognitive and emotional development of children and adolescents follows a
      biologically driven, environmentally mediated, and predictable but not entirely
      invariate sequence. Piagetian, psychoanalytic, and other schools of thought
      inform an understanding of child development; some of the theories are
      empirically validated, some not. This framework enables clinicians and parents to
      approach their children, ill or well, from a developmentally informed
      perspective. At the same time, as Spinetta's [17] case-controlled study of 6 to
      10-year-old children hospitalized either with cancer or non-life limiting illness
      demonstrated, serious illness itself accelerates cognitive development in often
      unpredicted ways: "To equate awareness of death with the ability to conceptualize
      it and express the concept in an adult man-ner denies the possibility of an
      awareness of death at a less cognitive level. If it is true that the perception
      of death can be engraved at some level that precedes a child's ability to talk
      about it, then a child might well understand that he is going to die long before
      he can say so." In the following articles,the editors invite a critical reading
      of the empiric and descriptive literature of pediatric palliative medicine that
      allows an informed and individualized approach to these extraordinary children
      and their families.

PMID- 16797439
TI  - From cure to palliation: managing the transition.
AB  - When a child is diagnosed with a life-threatening or life-limiting condition,
      their physical and affective world is immediately changed, regardless of the
      outcome of treatment. Pediatric care providers are in a unique position to offer
      hope to children and families even when cure is not possible. This hope focuses
      not only on cure, but incorporates the understanding that quality of life is not
      commensurate with length of life and that compassionate care can be provided in
      all stages of treatment.

PMID- 16797440
TI  - Psychotherapy in pediatric palliative care.
AB  - Psychotherapy for children who have life-threatening illness is unique in its
      challenges and rich in its rewards. Most of these children enter into
      psychotherapy because of the stress engendered by the illness rather than more
      general intrapsychic or interpersonal concerns. The facilitation of psychological
      adjustment is a common goal and brought about by managing anxiety related to
      great un-certainty and anticipatory grief. Siblings and other family members are
      incorporated into the work as they play a pivotal role in sustaining and
      strengthening emotional resources. Critical losses.around control, personal
      identity, and interpersonal relationships are common themes throughout the
      therapeutic process.

PMID- 16797441
TI  - Post-traumatic stress response to life-threatening illnesses in children and
      their parents.
AB  - Symptoms of PTSD have been reported in response to a variety of life-threatening
      medical illnesses and injuries in adults and children. Emerging data suggest that
      children often experience medical treatment and hospitalization as traumatic,
      putting caregivers and medical personnel in the role of the unintended
      accomplice. Adequate pain control by pharmacologic and behavioral means; child
      and family psychological support using evidence-based CBT, dynamic psychotherapy,
      and other techniques; and meticulous attention to communication via a team-based
      approach are the cornerstones of pediatric palliative care in general and PTSD
      prevention and treatment in particular. Emerging evidence suggests that PTSD in
      life-limiting pediatric illness can be ameliorated, if not prevented, and treated
      when it occurs, contributing materially to the quality of life of a child and
      family. A landmark finding of PTSD research with medically ill children and their
      families is that parents are at least as symptomatic, or more, as their children,
      underlining the importance of a family-directed approach addressing every family
      mem-ber. Pediatric caregivers increasingly recognize their therapeutic role when
      curative therapy is no longer possible is as pivotal as in the setting of acute
      illness.

PMID- 16797442
TI  - Psychopharmacology in pediatric critical care.
AB  - Psychopharmacologic treatment in pediatric critical care requires a careful child
      or adolescent psychiatric evaluation, including a thorough review of the history
      of present illness or injury, any current or pre-existing psychiatric disorder,
      past history, and laboratory studies. Although there is limited evidence to guide
      psychopharmacologic practice in this setting, psychopharmacologic treatment is
      increasing in critical care, with known indications for treatment, benefits, and
      risks; initial dosing guidelines; and best practices. Treatment is guided by the
      knowledge bases in pediatric physiology, psycho-pharmacology, and treatment of
      critically ill adults. Pharmacologic considerations include pharmacokinetic and
      pharmcodynamic aspects of specific drugs and drug classes, in particular
      elimination half-life, developmental considerations, drug interactions, and
      adverse effects. Evaluation and management of pain is a key initial step, as pain
      may mimic psychiatric symptoms and its effective treatment can ameliorate them.
      Patient comfort and safety are primary objectives for children who are acutely
      ill and who will survive and for those who will not. Judicious use of
      psychopharmacolgic agents in pediatric critical care using the limited but
      growing evidence base and a clinical best practices collaborative approach can
      reduce anxiety,sadness, disorientation, and agitation; improve analgesia; and
      save lives of children who are suicidal or delirious. In addition to pain, other
      disorders or indications for psychopharmacologic treatment are affective
      disorders;PTSD; post-suicide attempt patients; disruptive behavior disorders
      (especially ADHD); and adjustment, developmental, and substance use disorders.
      Treating children who are critically ill with psychotropic drugs is an integral
      component of comprehensive pediatric critical care in relieving pain and
      delirium; reducing inattention or agitation or aggressive behavior;relieving
      acute stress, anxiety, or depression; and improving sleep and nutrition. In
      palliative care, psychopharmacology is integrated with psychologicapproaches to
      enhance children's comfort at the end of life. Defining how best to prevent the
      adverse consequences of suffering and stress in pediatric critical care is a goal
      for protocols and for new psychopharmacologic research [23,153].

PMID- 16797443
TI  - Pain in children who have life-limiting conditions.
AB  - Children and adolescents who have life-limiting conditions are vulnerableto acute
      and chronic pain problems. Many compounding and complicatingfactors often need to
      be explored in this setting. Barriers to effective painmanagement include poor
      assessment and measurement of pain anda lack of specialist knowledge. Fears
      regarding the use of opioids and theirassociation with the end of life must be
      addressed openly and with clarity.Day-to-day management should include continual
      appraisal of pain issuesif quality of life is to be maximized. Pain is a
      complicated phenomenon. The impact of pain and the compli-cated dynamic of
      suffering in children and young people who have life-lim-iting conditions must
      not be underestimated. The clinician must be vigilantand take responsibility for
      all aspects of pain management in these patients.

PMID- 16797444
TI  - Cognitive-behavioral interventions for physical symptom management in pediatric
      palliative medicine.
AB  - The alleviation of symptoms, with the ultimate intention of improvement of
      quality of life, is a fundamental component of pediatric palliative medi-cine.
      Psychological factors can exacerbate physical symptoms or influence the
      perception of symptoms in children with advanced disease. Cognitive-behavioral
      interventions have yielded positive outcomes for the management of symptoms
      across various disease populations. There is a paucity of evidence specific to
      the application of these interventions in pediatric palliation, although evidence
      based treatments developed through investigation of other disease populations can
      be applied in pediatric palliation. Children tend to be receptive to these
      noninvasive interventions, which can decrease fear and anxiety, increase self
      efficacy and sense of control, and improve overall coping. Continued
      investigation into the use of these interventions in pediatric palliation is
      encouraged.

PMID- 16797445
TI  - Multidisciplinary care of the dying adolescent.
AB  - The adolescent at the end of life poses a unique combination of challenges
      resulting from the collision of failing health with a developmental trajectory
      meant to lead to attainment of personal independence. Because virtually all
      spheres of the dying adolescent's life are affected, optimal palliative care for
      these young persons requires a multidisciplinary team whose members have a good
      understanding of their complementary roles and a shared commitment to providing
      well-coordinated care. Members of the team include the physician (to initiate and
      coordinate palliative care management); the nurse (to work collaboratively with
      the physician and adolescent, especially through effective patient advocacy); the
      psychologist (to assess and manage the patient's neurocognitive and emotional
      status); the social worker (to assess and optimize support networks); the
      chaplain (to support the adolescent's search for spiritual meaning); and the
      child life specialist (to facilitate effective communication in preparing for
      death). A crucial area for dying adolescents is medical decision making, where
      the full range of combined support is needed. By helping the young person
      continue to develop personal autonomy, the multidisciplinary team will enable
      even the dying adolescent to experience dignity and personal fulfillment.

PMID- 16797446
TI  - Nursing interventions in pediatric palliative care.
AB  - Caring for chronically ill children whose health is declining and thosechildren
      who are critically ill is stressful and can be overwhelming to bothhealthcare
      professionals and parents. Palliative care teams aim to providethe
      multidisciplinary and holistic support staff and families need. Families,nurses,
      and primary medical teams value the involvement of a pediatric pal-liative
      medicine team to improve the quality of living. The bedside nurse isa vital part
      of the support system and is ready and available to be presentwith the palliative
      care team to support families no matter what the circum-stances. Advocating for
      the patient; creating a culture of flexibility; antici-pating, identifying, and
      responding to the patient and family needs;fostering hope; and providing the
      support needed for the parents to makeinformed decisions, are keys to providing
      quality patient care. Nurses arein the position to positively influence each of
      these areas of patient care ina positive manner.

PMID- 16797448
TI  - Palliative medicine in neonatal and pediatric intensive care.
AB  - Patients and families in NICU and PICU settings can be well served by fundamental
      palliative care approaches during curative and end-of-life care.A wide variety of
      patients are suitable for these services. Although barriers exist to implementing
      these teams within the ICU, the concepts remain sound,and models for successful
      integration of practices in these settings exist.

PMID- 16797447
TI  - Program interventions for children at the end of life and their siblings.
AB  - An analogy may be drawn between readying a family for the birthof a child and
      readying a family for the death of a child. Both ex-periences bring about an
      intense fusion of the emotional, physical,and spiritual realms for those bearing
      witness. Preparation, com-munication, and collaboration are essential to provide
      optimalsupport for the children at the end of life, the parents, and thebrothers
      and sisters.

PMID- 16797449
TI  - Children facing the death of a parent: the experiences of a parent guidance
      program at the massachusetts general hospital cancer center.
AB  - Children facing the death of a parent are facing a major upheaval, a loss that
      will bring them emotional pain and will resonate in different ways at important
      points throughout their lives. Given the proper supports, most children can
      expect to adjust well to this enormous change and live happy,productive, and
      meaningful lives. Although some risk factors for poor adjustment are fixed, the
      parents themselves often can address others effectively. Clinicians can help the
      parents of these children facilitate their children's best possible adjustment by
      emphasizing the principles of facilitating communication, minimizing disruption,
      preserving family time, and at-tending to their legacy. Clinicians place their
      children's behaviors within the context of their developmental stage and help the
      parents find language and an approach that feels comfortable to them. The goal is
      to help parents re-locate their bearings and realize they can use the parenting
      skills they al-ready have. Guided by the goal of protecting their children, these
      parents can find purpose and strength. Reframing their circumstances as a painful
      and unavoidable challenge, but one that they can actively face, is organizing and
      fortifying for these families buffeted by loss.

PMID- 16797450
TI  - Relational learning in pediatric palliative care: transformative education and
      the culture of medicine.
AB  - The discrepancy between what is taught in formal educational settings and what is
      learned by practitioners in the informal flow of everyday practice has been
      called the hidden curriculum. In this article, the authors apply a well
      documented range of concerns about the hidden curriculum and the erosion of
      professionalism to the arena of pediatric palliative care education. The authors
      propose that educational initiatives must always be grounded in the charged
      existential space of relationships among children, families,and practitioners,
      because the learning that matters most occurs within these relationships. The
      authors present an educational approach, which they call relational learning, and
      offer some preliminary strategies educators may wish to foster this kind of
      learning in their own health care organizations.

PMID- 16797451
TI  - Global issues, local impact. Abstracts of the 39th Annual Conference of the
      Society for Nutrition Education. July 15-18, 2006, San Francisco, California,
      USA. Abstracts.

PMID- 16797452
TI  - Neurogenesis in the adult central nervous system.
AB  - Contrary to the long-held dogma, neurogenesis occurs throughout adulthood, and
      neural stem cells reside in the adult central nervous system (CNS) in mammals.
      The developmental process of the brain may thus never end, and the brain may be
      amenable to repair. Neurogenesis is modulated in a wide variety of physiological
      and pathological conditions, and is involved in processes such as learning and
      memory and depression. However, the relative contribution of newly generated
      neuronal cells to these processes, as well as to CNS plasticity, remains to be
      determined. Thus, not only neurogenesis contributes to reshaping the adult brain,
      it will ultimately lead us to redefine our knowledge and understanding of the
      nervous system.

PMID- 16797453
TI  - [Locomotor activity rhythms in two sympatric parasitoid insects: Eupelmus
      orientalis and Eupelmus vuilleti (Hymenoptera, Eupelmidae)].
AB  - With an automatic image analysis device, we studied the temporal distribution of
      the locomotor activity of E. orientalis and E. vuilleti during 24 h, and over
      several days to know whether the activity rhythms of these two Eupelmidae play a
      role in their competitive interactions. The analysis of locomotor activity
      rhythms of E. orientalis and E. vuilleti shows that the locomotor activity of
      both species presents daily cyclic variations. These two Eupelmidae have similar
      activity rhythms. Displacements of these parasitoids essentially take place
      during the photophase. But the activity of E. vuilleti is earlier, because the
      individuals of this species start their activity on average 4 to 5 h earlier than
      those of E. orientalis. E. vuilleti begins its displacements several hours before
      the onset of lighting, whereas E. orientalis is active only in the presence of
      the light. This shift of starting activity is thus a factor allowing these
      concurrent species to minimize their interactions during the cohabitation period
      in traditional granaries after the harvests of cowpea.

PMID- 16797454
TI  - [Potamotrygon marinae n. sp., a new species of freshwater stingrays from French
      Guiana (Myliobatiformes, Potamotrygonidae)].
AB  - Six specimens of freshwater stingrays from the French Guiana belonging to the
      genus Potamotrygon [S.W. Garman, On the pelvis and external sexual organs of
      selachians, with special reference to the new genera Potamotrygon and Disceus,
      Proc. Bost. Soc. nat. Hist. 19 (1877) 197-215], do not present characters that
      are typically shown by species to which they have been attributed. Five belong to
      a new species here named Potamotrygon marinae n. sp. This species is
      differentiated from the others by the feebly development of the prepelvic
      process, the development of the postorbital process as an enlarged blade, the
      unsegmented angular cartilage, the dorsal surface coloration composed of wide
      circular patches themselves formed by smaller pale patches, the almost dark
      coloration of the ventral surface tessellated with pale patches, and the small
      sized spiny tubercles situated in the middorsal region, before the caudal sting.

PMID- 16797455
TI  - [Fire and Pinus mugo Turra communities in the western Alps (Susa Valley, Italy)
      during the Lateglacial-Holocene transition: an evidence of refugia area].
AB  - In western Italian Alps, small distinct populations of Pinus mugo Turra raise
      some questions concerning its ecological status and dynamics in the occidental
      Alps. This note present new palaeobotanical data based on cone imprints of Pinus
      mugo, identified in travertine systems located in the Val di Susa and dated back
      to the Late Dryas (11506+/-66 BP) and the Early Holocene (10145+/-225 et 9475+/
      670 BP). Heliophilous species and charcoal fragments were also identified,
      testifying to the oldness of wildfires in this region. The data support the
      hypothesis that this zone was a refuge area of this pine during the last
      glaciation. Here we discuss about the postglacial dynamics of the Pinus mugo in
      the occidental Alps.

PMID- 16797456
TI  - [Palaeostructures of vegetation at the upper limit of forests in the inner French
      Alps].
AB  - The comparison of six pollen diagrams from French Alps allows us to reconstruct
      the past changes of vegetation structure at the upper limit of Subalpine range.
      Dense populations of Pinus cembra developed between 6500 and 2400 cal. BP, both
      in the southern Alps and the northern ones. Southern Alps seem however to be
      characterised by higher altitudinal limits, as shown by the past development of
      fir forests at 2080 m a.s.l. in the Ubaye valley. This study highlights the
      importance of taking in account local parameters in regional or continental
      reviews.

PMID- 16797457
TI  - Differences in pharmacokinetic and electroencephalographic responses to caffeine
      in sleep-sensitive and non-sensitive subjects.
AB  - The present study investigated pharmacokinetic and electroencephalographic
      responses to caffeine (140 mg) in two groups of healthy volunteers reporting, or
      not, caffeine-related sleep disturbances. Significant differences in caffeine
      consumption and smoking habits were observed between the two groups. Plasma
      samples were taken from each subject before (T0) and after caffeine intake at
      0.5, 1, 2, 4, 6 and 24 h. Three pharmacokinetic parameters: half-life (t1/2),
      maximum time (Tmax) and maximum plasma concentration (Cmax) were calculated from
      caffeine plasma concentration measurements determined by reversed phase HPLC
      analysis. Caffeine-sensitive subjects showed significantly greater half-life
      values when calculated on 24 h after the administration than tolerant subjects
      (p<0.05). Since the elimination kinetics were similar on the first 6 h after
      caffeine administration, the increased caffeine clearance observed overnight,
      when smoking was resumed in the control group, may indicate a short delay for the
      induction of hepatic cytochrome, reported here for the first time.
      Electrophysiological responses to caffeine, including vigilance and cortical
      activity, were assessed by ambulatory electroencephalographic (EEG) recorded
      during a period of 6 h before and after caffeine consumption. Following caffeine
      intake, the caffeine-intolerant subjects presented an increase in vigilance
      levels with faster peak alpha, beta frequency and lower delta and theta power
      when compared to tolerant subjects. Pharmacokinetic parameters and EEG data
      showed significant differences between sleep-sensitive and control subjects.
      These variations may be, in part, explained by cigarette smoking and the higher
      caffeine intake observed in the subjects of the control groups while caffeine
      sleep-sensitive subjects have a significantly lower caffeine intake, as already
      reported in previous studies on patients with sleep disturbances.

PMID- 16797458
TI  - Feasibility of an SUV normalization to 1 hour after the 18F-FDG injection.
AB  - The aim of this work was to reduce the SUV variability related to the time delay
      between 18F-FDG injection and the static PET acquisition, by means of a
      normalization to a 1-h time delay. Two static PET acquisitions separated by
      approximately 1 h were performed on each of 14 cancer patients, with SUVs on 22
      hypermetabolic lesions calculated for both scans. The pairs of SUVs were
      normalized to each other using the parameterized input function with one free
      parameter (alpha3). This optimized parameter was found by computing the value
      which yielded equal normalized SUV pairs, on average, over the whole series.
      Without normalization, SUVs measured at later scans were found to be
      significantly greater than the earlier ones: mean (+/- SD) ratio of 0.84 (+/
      0.08; range 0.69-0.97). After normalization, with an alpha3 value of 0.0257 min(
      1), as expected, the mean (+/- SD) ratio was 1.00 (+/-0.07; range 0.88-1.10).

PMID- 16797459
TI  - [Adaptation of organisms to extreme conditions of deep-sea hydrothermal vents].
AB  - The deep-sea hydrothermal vents are located along the volcanic ridges and are
      characterized by extreme conditions such as unique physical properties
      (temperature, pression), chemical toxicity, and absence of photosynthesis.
      However, life exists in these particular environments. The primary producers of
      energy and organic molecules in these biotopes are chimiolithoautotrophic
      bacteria. Many animals species live in intimate and complex symbiosis with these
      sulfo-oxidizing and methanogene bacteria. These symbioses imply a strategy of
      nutrition and a specific metabolic organization involving numerous interactions
      and metabolic exchanges, between partners. The organisms of these ecosystems have
      developed different adaptive strategies. In these environments many
      microorganisms are adapted to high temperatures. Moreover to survive in these
      environments, living organisms have developed various strategies to protect
      themselves against toxic molecules such as H2S and heavy metals.

PMID- 16797460
TI  - [Spatial heterogeneity of wind forcing: application to artificial reef
      functioning influenced by the circulation in the Bay of Marseilles, France].
AB  - In the frame of the largest French project of artificial production reefs,
      initiated by the city of Marseilles in 2001, the present study aimed at
      describing the hydrodynamic pattern of the coastal area considered, by the use of
      a 3D numerical modelling. Results were local wind statistics, bottom current
      fields and drifting particle maps. The knowledge of the hydrodynamic connexions
      between particle (such as larvae) sources or targeted areas linked to the reefs,
      allows us to explain the success or failure of the reefs' colonizing. Moreover,
      the study confirms the wind spatial variability and demonstrates the error
      resulting from the use of an average but locally absent wind direction.

PMID- 16797461
TI  - Sexual segregation in fallow deer: are mixed-sex groups especially unstable
      because of asynchrony between the sexes?
AB  - In gregarious ruminants, females and males tend to live in separate groups
      outside the rutting season. According to the 'activity budget' hypothesis, this
      is due to an activity asynchrony between the two sexes reducing the lifetime of
      mixed-sex groups. We tested this hypothesis in a fallow deer population. Activity
      asynchrony was more frequent in mixed-sex than in single-sex groups. In addition,
      mixed-sex groups had a higher probability of splitting-up than all-female groups,
      and they mainly split up into single-sex groups. However, activity asynchrony did
      not appear as a major cause of splitting-up.

PMID- 16797462
TI  - The economic costs of road traffic crashes: Australia, states and territories.
AB  - In this paper, we obtain detailed data on road traffic crash (RTC) casualties, by
      severity, for each of the eight state and territory jurisdictions for Australia
      and use these to estimate and compare the economic impact of RTCs across these
      regions. We show that the annual cost of RTCs in Australia, in 2003, was
      approximately Dollars 17 b, which is approximately 2.3% of the Gross Domestic
      Product (GDP). Importantly, though, there is remarkable intra-national variation
      in the incident rates of RTCs in Australia and costs range from approximately
      0.62 to 3.63% of Gross State Product (GSP). The paper makes two fundamental
      contributions: (i) it provides a detailed breakdown of estimated RTC casualties,
      by state and territory regions in Australia, and (ii) it presents the first sub
      national breakdown of RTC costs for Australia. We trust that these contributions
      will assist policy-makers to understand sub-national variations in the road toll
      better and will encourage further research on the causes of the marked
      differences between RTC outcomes across the states and territories of Australia.

PMID- 16797463
TI  - Risk of vehicle-pedestrian and vehicle-bicyclist collisions among children with
      disabilities.
AB  - OBJECTIVES: To examine the potential association between disability and risk of
      vehicle-pedestrian and vehicle-bicyclist collisions among children. METHODS: Data
      from the 2002 National Transportation Availability and Use Survey for Persons
      with Disabilities (NTAUSPD) were analyzed. RESULTS: Among 5019 persons who
      completed the survey, there were a total of 687 children between 5-17 years of
      age, including 299 respondents with and 388 without disabilities. After
      controlling for potential confounding variables, children with disabilities were
      more than five times more likely to have been hit by a motor vehicle as a
      pedestrian or bicyclist than children without disabilities (adjusted OR = 5.53,
      95% confidence interval (CI): 1.43-21.41). For all children, regardless of their
      disability status, children who reported having some difficulty with traffic had
      a significantly higher risk of collisions (adjusted OR = 50.71, 95% CI: 7.35
      349.86). The most commonly reported traffic difficulties for all children with
      and without disabilities were "Too few or missing sidewalks/paths," "Do not know
      when it's safe to cross," and "Insensitive/unaware drivers." CONCLUSIONS:
      Existing effective transportation safety interventions should be effective in
      reducing the risk of vehicle-pedestrian and vehicle-bicyclist collisions in
      children with disabilities. Future research and safety interventions should focus
      on how to promote the use of existing effective transportation safety
      interventions among children with disabilities and their families.

PMID- 16797464
TI  - Analysis of accident inequality of the Spanish fishing fleet.
AB  - There is at present a clear tendency to consider safety as a vital factor in the
      running of a country's fishing sector. However, the planning of the necessary
      resources and their adequate distribution according to the sector's needs is only
      possible if detailed information is available about the degree of concentration
      of the accidentality of that sector. In this context, the aim of this work is two
      fold: firstly, to formalise a methodology for the fishing sector of a country
      which allows the inequality in the concentration of accidents to be analysed; and
      secondly, to apply this methodology to the Spanish fishing fleet for the period
      1994-2002. Thus, indices are built by regions and by types of vessel for two
      variables: fishermen and vessels. Results are obtained both for the inequality in
      the concentration of accidents and their associated Lorenz curves and for the
      rates and elasticities of fishing sector accidents.

PMID- 16797465
TI  - The Risk Line: a special telephone line to provide means of reporting potential
      dangers and to increase public participation.
AB  - Injuries constitute a significant public health problem. There is a risk of
      injury in any environment in which persons are present. The purpose of this paper
      is to describe the development and experiences from the Risk Line. The Risk Line
      is a special telephone number to provide means of reporting potential risks for
      injuries and dangerous products and to increase public participation in injury
      reporting. Various strategies have been used to make the Risk Line well known in
      the population. Weekly reports on the risk of playground, traffic, recreational,
      and residential injuries and dangerous products have been distributed to those
      who are responsible for eliminating these hazards. The major risk environments
      reported were traffic, recreational, residential environments, and playgrounds.
      Seventy-seven percent of the reported hazards had been eliminated. A majority of
      the public (72%) who had phoned the Risk Line stated that they had become more
      observant and aware of risks for injuries. In conjunction with injury statistics
      and safety inspections, information from the Risk Line can contribute to give an
      improved overall picture of where priorities are needed in safety promotion and
      injury prevention work.

PMID- 16797466
TI  - Infected dogs as a risk factor in the transmission of human Trypanosoma cruzi
      infection in western Venezuela.
AB  - A total of 565 mongrel dogs from rural localities of Venezuela were examined by
      serological (DAT, IFAT and ELISA) and parasitological tests to address the status
      of Trypanosoma cruzi infection and to evaluate their role in the transmission of
      the infection to human population. The overall percentage of sero-positive
      infected dogs shown to be 67.6% (382/565):253 (61.7%) from 47 villages belonging
      to 8 states located at 4 different geographical regions of western Venezuela and
      129 (33.5%) dogs from 48 households located in areas where Chagas disease is
      endemic. From 101 sampled dogs living in close proximity to 30 acute chagasic
      patients, 84% expressed specific anti-T. cruzi antibodies (Ab) with 12 of them
      (14%) showing blood circulating parasites (BCP). In these houses a high
      proportion of sero-positive people (20%) and frequent indoor infestation by
      triatomine-bugs (70%) was also recorded. The analysis revealed that from the 47
      rural villages sampled during the study, 91.5% had the presence of T. cruzi sero
      positive dogs, ranging from 62% positive localities at the states of Falcon and
      Cojedes to 100% in the other six studied Venezuelan states. This demonstrates
      that T. cruzi-infected dogs are found throughout all the geographical regions of
      western Venezuela irrespective of their ecological differences. Molecular typing
      of T. cruzi isolates from infected dogs using ribosomal and mini-exon gene
      markers, revealed the presence of both T. cruzi I and T. cruzi II lineages. The
      coincidence in the circulation of T. cruzi II in dog and human populations at the
      same locality and at the same time is reported and its significance is discussed.
      The combined serological, parasitological, epidemiological and molecular data is
      gathered here to call the attention on the presence of infected dogs as a risk
      factor in the maintenance of T. cruzi as a source for infection to humans.

PMID- 16797467
TI  - Prediction of Plasmodium falciparum placental infection according to the time of
      infection during pregnancy.
AB  - Malarial infection during pregnancy leads to placental infection, a known risk
      factor for low birth weight. Whether the stage of pregnancy at infection has a
      differential influence on these effects is not clearly known, but may be of
      importance for prevention strategies, including intermittent preventive treatment
      of pregnant women. Malaria infection during early (before 20 weeks), middle (20
      28 weeks), or late (after 28 weeks) pregnancy was evaluated by logistic
      regression and receiver operating characteristics analysis in relation to
      placental infection in pregnant Senegalese women. Plasmodium falciparum
      infections during late pregnancy are strongly related to placental infection, as
      well as those that occur in middle pregnancy. Knowledge of parasitological events
      over the entire duration of pregnancy permits a highly accurate prediction of
      placental infection. Not only malaria infections during late pregnancy increase
      the likelihood of placental infection. The current policy of intermittent
      preventive treatment of pregnant women, which implies an initial antimalarial
      cure after 20 weeks of pregnancy, will not avoid early infections. An earlier
      initiation of malaria prevention might improve its efficacy.

PMID- 16797468
TI  - Peptide, domain, and DNA affinity selection in the identification and
      quantitation of proteins from complex biological samples.

PMID- 16797469
TI  - A miniaturized cell-based fluorescence resonance energy transfer assay for
      insulin-receptor activation.
AB  - This report describes the development, optimization, and implementation of a
      miniaturized cell-based assay for the identification of small-molecule insulin
      mimetics and potentiators. Cell-based assays are attractive formats for compound
      screening because they present the molecular targets in their cellular
      environment. A fluorescence resonance energy transfer (FRET) cell-based assay
      that measures the insulin-dependent colocalization of Akt2 fused with either cyan
      fluorescent protein or yellow fluorescent protein to the cellular membrane was
      developed. This ratiometric FRET assay was miniaturized into a robust, yet
      sensitive 3456-well nanoplate assay with Z' factors of approximately 0.6 despite
      a very small assay window (less than twofold full activation with insulin). The
      FRET assay was used for primary screening of a large compound collection for
      insulin-receptor agonists and potentiators. To prioritize compounds for further
      development, primary hits were tested in two additional assays, a biochemical
      time-resolved fluorescence resonance energy transfer assay to measure insulin
      receptor phosphorylation and a translocation-based imaging assay. Results from
      the three assays were combined to yield 11 compounds as potential leads for the
      development of insulin mimetics or potentiators.

PMID- 16797470
TI  - Online immunoaffinity liquid chromatography/tandem mass spectrometry
      determination of a type II collagen peptide biomarker in rat urine: Investigation
      of the impact of collision-induced dissociation fluctuation on peptide
      quantitation.
AB  - Proteolytic fragments of type II collagen, a major component of joint tissue,
      have recently been identified as biomarkers for osteoarthritis, a progressive
      disease associated with cartilage degeneration. A liquid chromatography/tandem
      mass spectrometry (MS/MS) assay that utilizes online immunoaffinity
      chromatography and column switching was developed in our laboratory for the
      neoepitope of type II collagen (NET2C). During method development, peptide
      collision-induced dissociation (CID) was found to be a significant source of
      assay variation, which exceeded 10% CV, despite the fact that a stable-isotope
      labeled (SIL) internal standard was used to minimize imprecision. This phenomenon
      was studied in detail using peptides and associated SIL internal standards of
      varying lengths and amino acid compositions. Variability in peptide CID
      necessitated the monitoring of multiple MS/MS transitions to obtain acceptable
      assay precision. The assay was subsequently validated to measure NET2C
      concentrations in rat urine over the range of 0.1 to 10 ng/mL. The interday
      accuracy and precision ranged from 3.9 to 13.1 (%CV) and 10.7 to 5.3 (%RE),
      respectively, across the range of validated concentrations. A specific
      application of the assay is presented in which the role of estrogen deficiency in
      the development and progression of osteoarthritis was investigated. In this
      study, the effect of estrogen on lowering NET2C concentrations in urine in
      ovariectomized rats was demonstrated.

PMID- 16797471
TI  - Benzo[a]pyrene-7,8-quinone-3'-mononucleotide adduct standards for 32P
      postlabeling analyses: detection of benzo[a]pyrene-7,8-quinone-calf thymus DNA
      adducts.
AB  - Benzo[a]pyrene-7,8-quinone (BPQ) is one of the reactive metabolites of the widely
      distributed archetypal polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P).
      The formation of BPQ from B[a]P through trans-7,8-dihydroxy-7,8-dihydroB[a]P by
      the mediation of aldo-keto reductases and its role in the genotoxicity and
      carcinogenesis of B[a]P currently are under extensive investigation. Toxicity
      pathways related to BPQ are believed to include both stable and unstable
      (depurinating) DNA adduct formation as well as reactive oxygen species. We
      previously reported the complete characterization of four novel stable BPQ
      deoxyguanosine (dG) and two BPQ-deoxyadenosine (dA) adducts (Balu et al., Chem.
      Res. Toxicol. 17 (2004) 827-838). However, the identification of BPQ-DNA adducts
      by 32P postlabeling methods from in vitro and in vivo exposures required 3'
      monophosphate derivatives of BPQ-dG, BPQ-dA, and BPQ-deoxycytidine (dC) as
      standards. Therefore, in the current study, BPQ adducts of dGMP(3'), dAMP(3'),
      and dCMP(3') were prepared. The syntheses of the BPQ-3'-mononucleotide standards
      were carried out in a manner similar to that reported previously for the
      nucleoside analogs. Reaction products were characterized by UV, LC/MS analyses,
      and one- and two-dimensional NMR techniques. The spectral studies indicated that
      all adducts existed as diastereomeric mixtures. Furthermore, the structural
      identities of the novel BPQ-dGMP, BPQ-dAMP, and BPQ-dCMP adducts were confirmed
      by acid phosphatase dephosphorylation of the BPQ-nucleotide adducts to the
      corresponding known BPQ-nucleoside adduct standards. The BPQ-dGMP, BPQ-dAMP, and
      BPQ-dCMP adduct standards were used in 32P postlabeling studies to identify BPQ
      adducts formed in vitro with calf thymus DNA and DNA homopolymers. 32P
      postlabeling analysis revealed the formation of 8 major and at least 10 minor
      calf thymus DNA adducts. Of these BPQ-DNA adducts, the following were identified:
      1 BPQ-dGMP adduct, 2 BPQ-dAMP adducts, and 3 BPQ-dCMP adducts. This study
      represents the first reported example of the characterization of stable BPQ-DNA
      adducts in isolated mammalian DNA and is expected to contribute significantly to
      the future BPQ-DNA adduct studies in vivo and thereby to the contribution of BPQ
      in B[a]P carcinogenesis.

PMID- 16797472
TI  - DNA methylation mapping by tag-modified bisulfite genomic sequencing.
AB  - A tag-modified bisulfite genomic sequencing (tBGS) method employing direct cycle
      sequencing of polymerase chain reaction (PCR) products at kilobase scale, without
      conventional DNA fragment cloning, was developed for simplified evaluation of DNA
      methylation sites. The method entails subjecting bisulfite-modified genomic DNA
      to a second-round PCR amplification employing GC-tagged primers. Qualitative
      results from tBGS closely correlated with those from conventional BGS (R=0.935,
      p=0.002). In application, the intertissue and interindividual CpG methylation
      differences in promoter sequence for two genes, CYP1B1 and GSTP1, were then
      explored across four human tissue types (peripheral blood cells, exfoliated
      buccal cells, paired nontumor-tumor lung tissues), and two lung cell types in
      culture (normal NHBE and malignant A549). Predominantly conserved methylation
      maps for the two gene promoters were apparent across donors and tissues. At any
      given CpG site, variation in the degree of methylation could be determined by the
      relative height of C and T peaks in the sequencing trace. Methylation maps for
      the GSTP1 promoter diverged between NHBE (unmethylated) and A549 (completely
      methylated) cells in a previously unexplored upstream region, correlating with a
      2.7-fold difference in GSTP1 mRNA expression (p<0.01). The tBGS method simplifies
      detailed methylation scanning of kilobase-scale genomic DNA, facilitating more
      ambitious genomic methylation mapping studies.

PMID- 16797473
TI  - Automated high-throughput process for site-directed mutagenesis, production,
      purification, and kinetic characterization of enzymes.
AB  - Site-directed mutagenesis followed by functional characterization is a widely
      used approach to obtain information on the structure-function relationship of
      proteins. Due to time and cost considerations, the number of amino acids studied
      is frequently reduced. To address the need for convenient parallel production of
      numerous point mutants of a protein, we developed an automated method to perform
      classical site-directed mutagenesis, protein purification, and characterization
      in a high-throughput manner. The process consists of a succession of six fully
      automated protocols that can be adapted to any automated liquid handling systems.
      Our procedure allows construction, validation, and characterization of hundreds
      of site-directed mutants of a given protein in just 4 days. The method is
      especially adapted to projects aiming at the study of unique or multiple mutants
      without the need to construct and screen large libraries of random mutants. The
      usefulness of the technique is illustrated by the construction and
      characterization of tens of single mutants of the penicillin-binding protein 2x
      (PBP2x) from Streptococcus pneumoniae. Moreover, seven mutations of PBP2x were
      obtained simultaneously in a single experiment with efficiency close to 90%.

PMID- 16797474
TI  - DNA quantification using EvaGreen and a real-time PCR instrument.

PMID- 16797475
TI  - Reevaluation of the Griess reaction: how much of a problem is interference by
      nicotinamide nucleotides?

PMID- 16797476
TI  - The intrinsic enzymatic activity of plasma procarboxypeptidase U (TAFI) can
      interfere with plasma carboxypeptidase N assays.

PMID- 16797477
TI  - Time-resolved fluorescence resonance energy transfer kinase assays using
      physiological protein substrates: applications of terbium-fluorescein and terbium
      green fluorescent protein fluorescence resonance energy transfer pairs.
AB  - Fluorescence-based kinase assays using peptide substrates are an established
      format for high-throughput screening and profiling of kinases. Among fluorescence
      based formats, time-resolved fluorescence resonance energy transfer (TR-FRET)
      using a lanthanide donor species has advantages over other fluorescent formats in
      being resistant to many types of optical interference such as autofluorescent
      compounds, scattered light from precipitated compounds, or colored compounds that
      absorb excitation or emission radiation ("color quenchers"). By taking advantage
      of the fact that acceptors such as fluorescein or green fluorescent protein (GFP)
      can be paired with a terbium donor in a TR-FRET assay, we have developed TR-FRET
      kinase assays that use physiologically relevant native protein substrates, either
      labeled with fluorescein or expressed as GFP fusions. Phosphorylation of the
      labeled protein substrate results in an increase in TR-FRET when incubated with a
      terbium-labeled antibody that specifically recognizes the phosphorylated product.
      Thus, a strategy of using terbium-based TR-FRET can be applied to develop kinase
      assays, and the unique properties of terbium lead to a high degree of flexibility
      with regard to specific assay design.

PMID- 16797478
TI  - Correlation between phenotypic characteristics of mononuclear cells isolated from
      human periapical lesions and their in vitro production of Th1 and Th2 cytokines.
AB  - The development and progression of periapical dental lesions, mediated by the
      specific immune response, are poorly understood. In these processes, an interplay
      of different proinflammatory and immunoregulatory cytokines is of crucial
      importance. OBJECTIVES: To examine the activation of T helper 1 (Th1) and Th2
      immune responses in 25 human periapical lesions based on the ex vivo production
      of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by mononuclear cells (PL
      MNC). METHODS: The levels of IFN-gamma and IL-4 in culture supernatants of PL
      MNC, determined by ELISA, were correlated with concentrations of these cytokines
      in cultures of control MNC from peripheral blood (PB-MNC), cellular composition
      of inflammatory cells and phenotypic characteristics of PL-MNC. RESULTS: We
      detected high levels of IFN-gamma in all samples, after cell stimulation with
      phorbol myristate acetate and Ca(2+) ionophore, that were not statistically
      different from the levels of IFN-gamma in PB-MNC cultures. IL-4 was detected in
      76% samples, but its concentrations were much lower than in PB-MNC samples. The
      levels of IFN-gamma were higher in cultures of PL-MNC isolated from periapical
      lesions with predominance of T cells (T-type lesions) and correlated positively
      with the proportion of antigen-presenting cells (macrophages and dendritic
      cells), CD4(+) T cells and IgG2(+) B cells/plasma cells. The levels of IL-4
      correlated negatively with the proportion of macrophages, but positively with the
      number of mast cells and IgG4(+) cells. IL-18Ralpha, a stable marker of Th1
      cells, was detected on a relatively small proportion of CD3(+) T cells and its
      expression correlated with the levels of IFN-gamma. However, the expression of
      ST2L, a stable Th2 cell marker, was not detected. The levels of Th1 and Th2
      cytokines did not correlate with clinical characteristics of the lesions, defined
      by the presence of symptoms. CONCLUSION: Cumulatively, our results suggest the
      predominance of Th1 immune response in periapical lesions.

PMID- 16797479
TI  - The inhibitory effect of magnolol from Magnolia officinalis on
      glucosyltransferase.
AB  - Dental caries has been an intractable disease in spite of intense dental
      research. Glucosyltransferase (GTF) enzyme plays the most important role in the
      development of dental caries. In our previous studies, magnolol, a compound from
      Magnolia officinalis Rehder et Wilson (Magnoliaceae), was shown to possess a
      strong anti-GTF activity. The purpose of the present study was to examine the
      effect of magnolol on the functional domains of GTF for the purpose of defining
      its anti-GTF activity mechanism. GTF-I which was prepared from Streptococcus
      milleri transformant KSB8 cells expressing the gtfB gene was used. The results
      demonstrated magnolol reduced total glucan synthesis, depending on the magnolol
      concentration. There were no significant differences in Michaelis constant (K(m))
      values between the presence and absence of magnolol as determined by Lineweaver
      Burk plot, and maximum velocity (V(m)) in the presence of magnolol was lower than
      that in its absence. Magnolol significantly inhibited both sucrose hydrolysis and
      glucosyl transfer to glucan by GTF-I. Free glucose in the presence of magnolol
      was reduced by 33-48% as compared to in its absence, while the quantity of glucan
      was reduced by 75-82%. These findings suggested that magnolol inhibited both two
      sequential reaction phases of GTF non-competitively by operating on the glucan
      binding domain, but not on the catalytic domain. Magnolol could be a valuable
      resource for the exploration of novel bioactive compounds in natural products.

PMID- 16797480
TI  - Redox stress is not essential for the pseudo-hypoxic phenotype of succinate
      dehydrogenase deficient cells.
AB  - HIFalpha prolyl hydroxylases (PHDs) are a family of enzymes that regulate protein
      levels of the alpha subunit of the hypoxia inducible transcription factor (HIF)
      under different oxygen levels. PHDs catalyse the conversion of a prolyl residue,
      molecular oxygen and alpha-ketoglutarate to hydroxy-prolyl, carbon dioxide and
      succinate in a reaction dependent on ferrous iron and ascorbate as cofactors.
      Recently it was shown that pseudo-hypoxia, HIF induction under normoxic
      conditions, is an important feature of tumours generated as a consequence of
      inactivation of the mitochondrial tumour suppressor 'succinate dehydrogenase'
      (SDH). Two models have been proposed to describe the link between SDH inhibition
      and HIF activation. Both models suggest that a mitochondrial-generated signal
      leads to the inhibition of PHDs in the cytosol, however, the models differ in the
      nature of the proposed messenger. The first model postulates that mitochondrial
      generated hydrogen peroxide mediates signal transduction while the second model
      implicates succinate as the molecular messenger which leaves the mitochondrion
      and inhibits PHDs in the cytosol. Here we show that pseudo-hypoxia can be
      observed in SDH-suppressed cells in the absence of oxidative stress and in the
      presence of effective antioxidant treatment.

PMID- 16797481
TI  - Infrared micro-spectroscopic studies of epithelial cells.
AB  - We report results from a study of human and canine mucosal cells, investigated by
      infrared micro-spectroscopy, and analyzed by methods of multivariate statistics.
      We demonstrate that the infrared spectra of individual cells are sensitive to the
      stage of maturation, and that a distinction between healthy and diseased cells
      will be possible. Since this report is written for an audience not familiar with
      infrared micro-spectroscopy, a short introduction into this field is presented
      along with a summary of principal component analysis.

PMID- 16797482
TI  - Molecular cloning and characterization of ouabain-insensitive Na(+)-ATPase in the
      parasitic protist, Trypanosoma cruzi.
AB  - Maintaining low intracellular sodium concentrations is vital for almost all
      organisms. Na(+) efflux is generally governed by P-type ATPases, Na(+)/K(+)
      ATPase in animals and Na(+)-ATPase, called ENA, in fungi and plants. Trypanosoma
      cruzi, which parasitizes mammalian cells, must undergo drastic adaptations to
      high Na(+) concentrations outside and low Na(+) concentrations inside host cells.
      However, T. cruzi Na(+) efflux pumps have not been identified. We report here the
      cloning and characterization of the gene encoding Na(+)-ATPase in T cruzi, which
      resembled fungal and plant ENAs, termed TcENA. TcENA was a plasma membrane
      protein expressed throughout the parasite life cycle. The transcription level of
      TcENA was higher in insect stage epimastigotes and blood stream trypomastigotes
      than in intracellular amastigotes, probably reflecting the high Na(+)
      concentration outside the host cells. Biochemical analysis of TcENA expressed
      heterologously in mammalian cells demonstrated, for the fist time, that the
      ATPase activity of TcENA is stimulated by both Na(+) and K(+) and is insensitive
      to ouabain, a specific inhibitor of Na(+)/K(+)-ATPases. Furthermore,
      epimastigotes overproducing TcENA showed increased tolerance to high Na(+)
      stress. Our findings suggest that TcENA acts as a sodium pump and provide
      insights into the regulation of ion homeostasis in the parasitic protist.

PMID- 16797483
TI  - Panic and avoidance in panic disorder with agoraphobia: clinical relevance of
      change in different aspects of the disorder.
AB  - Different aspects of change were examined in 62 patients who fulfilled the DSM-IV
      criteria for a primary diagnosis of panic disorder with agoraphobia of moderate
      to severe magnitude, and who were treated with 16 sessions of behavioral therapy.
      The treatment resulted in substantial effects on panic attacks and agoraphobic
      avoidance. Panic-free status only differentiated the patients regarding mood at
      pre- and post-treatment. Changes in panic and avoidance were related to each
      other, but change in avoidance was more related to change in negative affect.
      Change in quality of life (QOL) was also more associated with change in avoidance
      at post-treatment. At follow-up change in QOL was more related to change in panic
      than change in avoidance.

PMID- 16797484
TI  - An experimental investigation of the cognitive vulnerability to depression.
AB  - The present study employed an experimental design, to examine the role of
      metacognitive processing in the prevention of relapse to depression. Eighty
      remitted depressed participants were randomly allocated to receive training in
      the metacognitive style of rumination, distraction, acceptance or no training
      control prior to a negative mood induction. Rumination prolonged the intensity of
      the negative mood consistent with no training, whereas both distraction and
      acceptance reduced the intensity of the negative mood. Changes in attitudes were
      only found in the acceptance condition, as participants in this condition reduced
      negative attitudes towards negative experiences. These results are consistent
      with information processing theory, and imply that acceptance-based preventative
      interventions may operate by both reducing the intensity of sad moods and
      altering one's attitudes towards temporary moments of sadness.

PMID- 16797485
TI  - Threat is in the eye of the beholder: social anxiety and the interpretation of
      ambiguous facial expressions.
AB  - The current study investigated the tendency of individuals with high levels of
      social anxiety to interpret ambiguous facial expressions in a threatening manner.
      Results obtained from self-report measures were consistent with previous studies
      in which highly socially anxious individuals endorsed threatening interpretations
      for ambiguous social information. More importantly, highly socially anxious
      participants showed relative facilitation of processing of threatening faces
      following neutral faces when a priming technique was used to eliminate artifact
      due to response selection bias. These findings support the hypothesized social
      anxiety-linked interpretive bias.

PMID- 16797486
TI  - Treatment-resistant depressed patients show a good response to Mindfulness-based
      Cognitive Therapy.
AB  - Mindfulness-based Cognitive Therapy (MBCT) is a class-based programme designed
      for use in the prevention of relapse of major depression. Its aim is to teach
      participants to disengage from those cognitive processes that may render them
      vulnerable to future episodes. These same cognitive processes are also known to
      maintain depression once established, hence a clinical audit was conducted to
      explore the use of MBCT in patients who were currently actively depressed, and
      who had not responded fully to standard treatments. The study showed that it was
      acceptable to these patients and resulted in an improvement in depression scores
      (pre-post Effect Size=1.04), with a significant proportion of patients returning
      to normal or near-normal levels of mood.

PMID- 16797487
TI  - Is thought-action fusion related to religiosity? Differences between Christians
      and Jews.
AB  - The purpose of this study was to evaluate the relationship between thought-action
      fusion (TAF) and religiosity in Christians and Jews (Orthodox, Conservative, and
      Reform). There is a growing body of evidence that suggests that religiosity is
      related to obsessive cognitions in Christian samples, but conceptual and
      empirical ambiguities complicate the interpretation of that literature and its
      application to non-Christian groups. As predicted on the basis of previous
      research, Christians scored higher than Jews on moral TAF. This effect was large
      and not explained by differences in self-reported religiosity. The Jewish groups
      did not differ from each other. Furthermore, religiosity was significantly
      associated with TAF only within the Christian group. These results qualify the
      presumed association between religiosity and obsessive cognitions. General
      religiosity is not associated with TAF; it rather depends on what religious
      group. Moreover, large group differences in a supposed maladaptive construct
      without evidence of corresponding differences in prevalence rates call into
      question the assumption that TAF is always a marker of pathology.

PMID- 16797488
TI  - Phosphorylation of serine 709 in GIT1 regulates protrusive activity in cells.
AB  - G protein-coupled receptor kinase-interacting protein (GIT)1 is a multidomain,
      adaptor protein that regulates cellular processes, such as migration and
      protrusive activity, by bringing together various signaling molecules, including
      PIX, PAK, and paxillin. Mutants of GIT1, which lack the C-terminal paxillin
      binding domain, fail to mediate its effects on migration and protrusions,
      suggesting that sites within this domain are critical to GIT1 function. In this
      study, we show that serine 709, which is located within the paxillin binding
      domain, regulates GIT1 function. Phosphorylation of serine 709 is necessary for
      GIT1-induced effects on protrusions. Phosphorylation of this site also regulates
      GIT1 interaction with paxillin, which could serve to target GIT1 to the leading
      edge of cells. As shown by an in vitro kinase assay, PAK phosphorylates GIT1 on
      serine 709. Taken together, our results indicate that GIT1 phosphorylation on
      serine 709 increases its binding to paxillin and regulates protrusive activity in
      cells.

PMID- 16797489
TI  - KR-62980: a novel peroxisome proliferator-activated receptor gamma agonist with
      weak adipogenic effects.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      is the target for the anti-diabetic drugs including thiazolidinediones. We report
      here the identification and characterization of a novel PPARgamma agonist KR
      62980. KR-62980 acted as a selective PPARgamma agonist in transactivation assay
      with an EC50 of 15 nM. In fully differentiated 3T3-L1 adipocytes, KR-62980
      induced [3H]-deoxyglucose uptake in a concentration-dependent manner in the
      presence of insulin. KR-62980 was weakly adipogenic with little induction of aP2
      mRNA, and was able to antagonize the adipogenic effects of rosiglitazone in
      C3H10T1/2 cells. In vivo pharmacokinetic profile of KR-62980 revealed that the
      compound exhibited good oral bioavailability of 65% with a terminal elimination
      half-life of 2.5 h in the rat. Treatment of high fat diet-induced C57BL/6J mice
      with KR-62980 for 14 days reduced plasma glucose levels with little side effects
      with regard to weight gain, cardiac hypertrophy and hepatotoxicity. These results
      suggest that KR-62980 acts as a selective PPARgamma modulator with anti
      hyperglycemic activity, and that the mechanism of actions of KR-62980 appears to
      be different from that of rosiglitazone with improved side effect profiles.

PMID- 16797490
TI  - Molecular targets for emerging anti-tumor therapies for neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome.
      NF1 patients present with a constellation of clinical manifestations and have an
      increased risk of developing certain benign and malignant tumors. This disease
      results from mutation within the gene encoding neurofibromin, a GTPase activating
      protein (GAP) for Ras. Functional loss of this protein compromises Ras
      inactivation, which leads to the aberrant growth and proliferation of neural
      crest-derived cells and, ultimately, tumor formation. Current management of NF1
      associated malignancy involves radiation, surgical excision, and cytotoxic drugs.
      The limited success of these strategies has fueled researchers to further
      elucidate the molecular changes that drive tumor formation and progression. This
      discussion will highlight how intracellular signaling molecules, cell-surface
      receptors, and the tumor microenvironment constitute potential therapeutic
      targets, which may be relevant not only to NF1-related malignancy but also to
      other human cancers.

PMID- 16797491
TI  - Heterotopic inputs facilitate poststimulus afterdischarges of spinal WDR neurons
      in rats with chronic nerve constriction.
AB  - Heterotopic inputs activate spinal wide dynamic range (WDR) neurons in rats with
      chronic constriction of one sciatic nerve (CCI rats). A possible contribution
      from these inputs, to long-lasting afterdischarges (ADs) of noxious evoked
      responses, was investigated during reversible input blockade from adjacent
      saphenous nerve and contralateral peripheral nerve territories. The results show
      significant AD reduction or suppression, indicating that heterotopic afferences
      contribute to mechanisms underlying prolonged ADs.

PMID- 16797492
TI  - Proteomic analysis identifies alterations in cellular morphology and cell death
      pathways in mouse brain after chronic corticosterone treatment.
AB  - Some patients with Major Depression and other neurological afflictions display
      hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. HPA hyperactivity
      may be due to impaired feedback inhibition and manifested as increased levels of
      circulating cortisol. Subcutaneous implants of corticosterone pellets were used
      to mimic this situation in mice to gain insight into any effects on brain
      function by comparative proteomic analysis using two-dimensional Differential In
      Gel Electrophoresis. A total of 150 different protein spots were altered by
      corticosterone treatment in the hypothalamus, hippocampus and cerebral cortex. Of
      these, 117 spots were identified by matrix-assisted laser desorption/ionization
      time of flight mass fingerprinting equating to 51 different proteins. Association
      of these corticosterone-modulated proteins with biological functions using the
      Ingenuity Pathways Analysis tool showed that cell morphology was significantly
      altered in the hippocampus and cerebral cortex, whereas the hypothalamus showed
      significant changes in cell death. Ingenuity Pathways Analysis of the canonical
      signaling pathways showed that glycolysis and gluconeogenesis were altered in the
      hypothalamus and the hippocampus and all three brain regions showed changes in
      phenylalanine, glutamate and nitrogen metabolism. Further elucidation of these
      pathways could lead to identification of biomarkers for the development of
      pharmacological therapies targeted at neuropsychiatric disorders.

PMID- 16797493
TI  - Spatial and temporal patterns of proliferation and differentiation in the
      developing turtle eye.
AB  - Here we show for the first time different aspects of the pattern of neurogenesis
      in the developing turtle retina by using different morphological and molecular
      clues. We show the chronotopographical fashion of occurrence of three major
      aspects of retinal development: (1) morphogenesis of the optic primordia and
      emergence of the different retinal layers, (2) the temporal progression of
      neurogenesis by the cessation of proliferative activity, and (3) the apparition
      and cellular localization of different antigens and neuroactive substances.
      Retinal cells were generated in a conserved temporal order with ganglion cells
      born first, followed by amacrine, photoreceptor, horizontal and bipolar/Muller
      cells. While eventually expressed in many types of retinal neurons, Islet1 was
      permanently expressed in differentiating and mature ganglion cells. Calbindin
      immunoreactive elements were found in the ganglion cell layer and the inner
      nuclear layer. Interestingly, at later stages the amount of expressing cells in
      these layers was reduced dramatically. On the contrary, the number of calbindin
      immunoreactive photoreceptors increased as development proceeded. In addition,
      calretinin expressing cells were prominent in the horizontal cell bodies, and
      their processes extending into the outer plexiform layer were also strongly
      labeled. Finally, the synthesis of gamma-aminobutyric acid (GABA) was detected in
      developing and matured horizontal and amacrine cells. All these maturational
      features began in the dorso-central area, in a region slightly displaced towards
      the temporal retina.

PMID- 16797494
TI  - The selective mu opioid receptor antagonist, alvimopan, improves delayed GI
      transit of postoperative ileus in rats.
AB  - Postoperative ileus (POI) is often exacerbated by opioid analgesic use during and
      following surgery, since mu opioid receptor activation results in a further delay
      of gastrointestinal (GI) transit. The effects of alvimopan, a novel, selective,
      and peripherally acting mu opioid receptor antagonist, and the reference compound
      methylnaltrexone, upon POI were investigated in rats. Under isoflurane
      anesthesia, POI was induced by laparotomy with intestinal manipulation.
      Immediately after the surgery, the rats received (51)Cr by gavage. Three hours
      after the surgery, the rats were sacrificed and GI transit was estimated using
      the geometric center (GC) of (51)Cr. Alvimopan (0.1-3 mg/kg) or methylnaltrexone
      (100 mg/kg) were administered by gavage either before or after the surgery, with
      or without morphine administration (1 mg/kg). GI transit was delayed by
      intestinal manipulation (GC = 2.92 +/- 0.17). Alvimopan (1 and 3 mg/kg)
      significantly reversed this delayed GI transit when administered 45 min prior to
      surgery. However, the effects of alvimopan were less pronounced when administered
      following surgery. Morphine administration further delayed GI transit induced by
      intestinal manipulation (GC = 1.97 +/- 0.11). Under these conditions, alvimopan
      (1 and 3 mg/kg) also significantly improved delayed GI transit when administered
      before surgery. Methylnaltrexone was inactive under all experimental conditions.
      These data suggest that mu opioid receptors play a role in the pathogenesis of
      POI, and that the clinical benefit reported to be afforded by alvimopan may be in
      part mediated via inhibition of an endogenous opioid release as well as blockade
      of the unwanted GI actions of analgesic agents.

PMID- 16797495
TI  - Visuomotor integration is impaired in early stage Alzheimer's disease.
AB  - When the sensory information guiding a reach movement is dissociated from the
      required motor output, humans must integrate rule-based information in order to
      reach accurately. Here, we examine the accuracy of movements requiring a
      visuomotor transformation in neurologically healthy elderly subjects and patients
      diagnosed with probable Alzheimer's disease. Participants made sliding finger
      movements over a clear touch-sensitive screen positioned in three spatial planes
      to displace a cursor from a central target to one of four peripheral targets
      viewed on a monitor. These spatial plane conditions were repeated under
      conditions where the direction of cursor motion was rotated 180 degrees relative
      to the direction of hand motion. Significant main effects were observed between
      patient and control groups on reaction time and movement time measures. Also,
      significant increases in task completion errors were observed in the patient
      population. Further, performance was affected more by the visual feedback changes
      relative to the plane location changes. Notably, there were substantial
      performance deficits observed in the patient population, even those with minimal
      cognitive deficits. We suggest that the integration of eye and hand information
      may be impaired in these patients.

PMID- 16797496
TI  - Enhancement of neuroprotection and heat shock protein induction by combined
      prostaglandin A1 and lithium in rodent models of focal ischemia.
AB  - Both prostaglandin A(1) (PGA(1)) and lithium have been reported to protect
      neurons against excitotoxic and ischemic injury. The present study was undertaken
      to examine the effects of lithium and PGA1 on heat shock proteins (HSP) and the
      growth arrest and DNA-damage-inducible gene (GADD153) and to evaluate if lithium
      could potentiate PGA(1)'s neuroprotective effects against cerebral ischemia. Rats
      were pretreated with a subcutaneous injection of lithium for 2 days and a single
      intracerebral ventricle administration of PGA(1) 15 min before ischemic insult.
      Brain ischemia was induced by a permanent middle cerebral artery occlusion. The
      infarct volume, motor behavior deficits and brain edema were analyzed 24 h after
      ischemic insult. The result showed that PGA(1) significantly reduced infarct
      volume, neurological deficits and brain edema. Except for neurological deficit,
      lithium enhanced PGA(1)'s neuroprotection. The neuroprotective effects of PGA(1)
      were associated with an up-regulation of cytoprotective heat shock proteins HSP70
      and GRP78 in the ischemic brain hemisphere as determined by immunoblotting and
      immunofluorescence. The induction of HSP70 and GRP78 was enhanced by lithium.
      However, although the expression of GADD153 was enhanced significantly after
      pMCAO, it was not influenced by either PGA(1) or lithium or their combination.
      These studies suggest that lithium can potentiate PGA(1)'s neuroprotective
      effects and thus may have potential clinical value for the treatment of stroke in
      combination with other neuroprotective agents.

PMID- 16797497
TI  - Stem cell marker expression in the Bergmann glia population of the adult mouse
      brain.
AB  - Recent evidence suggests that the postnatal cerebellum contains cells with
      characteristics of neural stem cells, which had so far only been identified in
      the subventricular zone of the lateral ventricles and the subdentate gyrus of the
      hippocampus. In order to investigate the identity of these cells in the adult
      cerebellum, we have analyzed the expression of Sox1, a transcription factor from
      the SoxB1 subgroup and widely used marker of neural stem cells. In situ
      hybridization and the use of a transgenic mouse model show that, in the adult
      cerebellum, Sox 1 is only expressed in the Bergmann glia, a population of radial
      glia present in the Purkinje cell layer. Furthermore, another neural stem cell
      marker, Sox2 (also member of the SoxB1 subgroup), is also expressed in the
      Bergmann glia. We have previously shown that these same cells express Sox9, a
      member of the SoxE subgroup known for its role in glial development. Here we show
      that Sox9 is in fact also expressed in other regions harboring adult neural stem
      cells, suggesting that Sox9 represents a novel stem cell marker. Finally, using a
      Sox1-null mouse, we show that the formation of this Sox2/Sox9 positive Bergmann
      glia population does not require the presence of a functional Sox1. Our results
      identify these radial glia as a previously unreported Sox1/Sox2/Sox9 positive
      adult cell population, suggesting that these cells may represent the recently
      reported stem cells in the adult cerebellum.

PMID- 16797498
TI  - Interactions between opioid-peptides-containing pathways and GABA(A)-receptors
      mediated systems modulate panic-like-induced behaviors elicited by electric and
      chemical stimulation of the inferior colliculus.
AB  - Aiming to clarify the effect of interactive interconnections between the
      endogenous opioid peptides-neural links and GABAergic pathways on panic-like
      responses, in the present work, the effect of the peripheral and central
      administration of morphine or the non-specific opioid receptors antagonist
      naloxone was evaluated on the fear-induced responses (defensive attention,
      defensive immobility and escape behavior) elicited by electric and chemical
      stimulation of the inferior colliculus. Central microinjections of opioid drugs
      in the inferior colliculus were also performed followed by local administration
      of the GABA(A)-receptor antagonist bicuculline. The defensive behavior elicited
      by the blockade of GABAergic receptors in the inferior colliculus had been
      quantitatively analyzed, recording the number of crossing, jump, rotation and
      rearing, in each minute, during 30 min, in the open-field test. The opioid
      receptors stimulation with morphine decreased the defensive attention, the
      defensive immobility and escape behavior thresholds, and the non-specific opioid
      receptors blockade caused opposite effects, enhancing the defensive behavior
      thresholds. These effects were corroborated by either the stimulation or the
      inhibition of opioid receptors followed by the GABA(A) receptor blockade with
      bicuculline, microinjected into the inferior colliculus. There was a significant
      increase in the diverse fear-induced responses caused by bicuculline with the
      pretreatment of the inferior colliculus with morphine, and the opposite effect
      was recorded after the pretreatment of the inferior colliculus nuclei with
      naloxone followed by bicuculline local administration. These findings suggest an
      interaction between endogenous opioid-peptides-containing connections and GABA(A)
      receptor-mediated system with direct influence on the organization of the panic
      like or fear-induced responses elaborated in the inferior colliculus during
      critical emotional states.

PMID- 16797500
TI  - Cardiovascular effects of adrenocorticotropin microinjections into the rostral
      ventrolateral medullary pressor area of the rat.
AB  - The presence of adrenocorticotropic hormone (ACTH)-immunoreactive cells and
      melanocortin (MC) receptors (MC4 and to a lesser extent MC3) has been
      demonstrated in the medullary reticular formation in the general area where
      rostral ventrolateral medullary pressor area (RVLM) is located. The importance of
      RVLM in the regulation of cardiovascular function is well established. Based on
      these reports, it was hypothesized that ACTH may play a role in the regulation of
      cardiovascular function. To test this hypothesis, experiments were carried out on
      artificially ventilated, adult male, urethane-anesthetized and unanesthetized mid
      collicular decerebrate rats. The RVLM was identified by microinjections (100 nl)
      of L-glutamate (L-Glu). Microinjections (100 nl) of ACTH (0.5, 1 and 2 mmol/l)
      into the RVLM elicited increases in MAP and HR; tachycardic responses were
      relatively inconsistent. The effects of ACTH were blocked by SHU9119 and agouti
      related protein (AGRP). SHU9119 (a synthetic compound) and AGRP (an endogenous
      peptide) are antagonists for MC4, and to a lesser extent MC3, receptors. The
      specificity of these antagonists for MC receptors was indicated by their lack of
      effect on l-Glu responses. Microinjection of ACTH into the RVLM increased the
      efferent discharge in the greater splanchnic nerve. It was concluded that (1)
      ACTH exerts excitatory effects on RVLM neurons resulting in pressor and
      tachycardic responses, (2) these responses were mediated via MC4 and to a lesser
      extent MC3 receptors in the RVLM, and (3) the pressor effects of ACTH were
      mediated via sympathetic activation. This is the first report showing central
      cardiovascular actions of ACTH.

PMID- 16797499
TI  - BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back
      propagating action potentials in CA1 pyramidal neurons.
AB  - BDNF, a member of the neurotrophin family, is emerging as a key modulator of
      synaptic structure and function in the CNS. Due to the critical role of
      postsynaptic Ca(2+) signals in dendritic development and synaptic plasticity, we
      tested whether long-term exposure to BDNF affects Ca(2+) elevations evoked by
      coincident excitatory postsynaptic potentials (EPSPs) and back-propagating action
      potentials (bAPs) in spiny dendrites of CA1 pyramidal neurons within hippocampal
      slice cultures. In control neurons, a train of 5 coincident EPSPs and bAPs evoked
      Ca(2+) elevations in oblique radial branches of the main apical dendrite that
      were of similar amplitude than those evoked by a train of 5 bAPs alone. On the
      other hand, dendritic Ca(2+) signals evoked by coincident EPSPs and bAPs were
      always larger than those triggered by bAPs in CA1 neurons exposed to BDNF for 48
      h. This difference was not observed after blockade of NMDA receptors (NMDARs)
      with D,L-APV, but only in BDNF-treated neurons, suggesting that Ca(2+) signals in
      oblique radial dendrites include a synaptic NMDAR-dependent component. Co
      treatment with the receptor tyrosine kinase inhibitor k-252a prevented the effect
      of BDNF on coincident dendritic Ca(2+) signals, suggesting the involvement of
      neurotrophin Trk receptors. These results indicate that long-term exposure to
      BDNF enhances Ca(2+) signaling during coincident pre- and postsynaptic activity
      in small spiny dendrites of CA1 pyramidal neurons, representing a potential
      functional consequence of neurotrophin-mediated dendritic remodeling in
      developing neurons.

PMID- 16797501
TI  - Extension of the Nef reaction to C-glycosylnitromethanes.
AB  - Acid-catalysed methanolysis of 3,4,5,6-tetra-O-acetyl-1,2-dideoxy-l-arabino-hex-1
      enitol proceeds via a cascade set of consecutive reactions resulting in its
      regiospecific conversion to a mixture of alpha- and beta-C-L
      arabinofuranosylmethanal dimethyl acetals and a mixed internal methyl acetal.
      Structures of the final products of the overall process provide unique evidence
      that a kinetically controlled, five-membered-ring closure precedes a six-membered
      ring closure in reversible systems capable of giving both five-membered and six
      membered all-sp3-atom rings. Determination of the reaction intermediate enabled
      extension of the Nef reaction to C-glycosylnitromethanes. Protonated aci-nitro
      forms of C-glycosylnitromethanes that are resistant to the Nef reaction in
      aqueous acidic media undergo a modified Nef reaction in acidified methanol, and
      the corresponding C-glycosylmethanal dimethyl acetals with alpha-L
      arabinopyranosyl, beta-D-glucopyranosyl, beta-D-galactopyranosyl, beta-D
      mannopyranosyl and beta-L-rhamnopyranosyl configurations were obtained in
      moderate yields.

PMID- 16797502
TI  - Regioselective esterase-catalyzed feruloylation of L-arabinobiose.
AB  - The regioselective chemoenzymatic synthesis of O-[5-O-(trans-feruloyl)-alpha-L
      arabinofuranosyl]-(1-->5)-L-arabinofuranose has been achieved. The reaction
      parameters affecting the feruloylation rate and conversion of the enzymatic
      synthesis, such as the composition of the reaction medium, substrate and enzyme
      concentration, have been investigated.

PMID- 16797503
TI  - Estradiol blocks the induction of CD40 and CD40L expression on endothelial cells
      and prevents neutrophil adhesion: an ERalpha-mediated pathway.
AB  - OBJECTIVE: Interferon gamma (IFN-gamma) was shown to induce CD40 and CD40L
      expression on endothelial cells (ECs) and consequently to promote neutrophil
      adhesion. The pro- and anti-inflammatory effects of estrogens are well recognized
      but their role on the regulation of CD40 and CD40L expression on ECs remains
      undefined. METHODS AND RESULTS: Treatment of porcine aortic endothelial cells
      (PAEC) with IFN-gamma for 24 h enhanced CD40 and CD40L expression by 97% and 78%,
      respectively. Pretreatment of PAEC with 17-beta-estradiol (17betaE) for 24 h
      prevented the latter expression of CD40/CD40L. Treatment of PAEC with antisense
      oligomers targeting ERalpha mRNA attenuated the ability of 17betaE to inhibit the
      IFN-gamma-induced CD40 and CD40L protein expression. The IFN-gamma activation
      pathway of CD40 is known to involve the phosphorylation of the Janus activated
      kinase (JAK) and the signal transducer and activator of transcription 1 (Stat1).
      17betaE, acting via the estrogen receptor alpha (ERalpha), abrogated IFN-gamma
      mediated effects on Stat1 but failed to inhibit Jak1 and Jak2 phosphorylation.
      Furthermore, 17betaE prevented neutrophil adhesion induced by IFN-gamma.
      CONCLUSION: In summary, 17betaE binding to ERalpha blocked IFN-gamma-induced
      Stat1 phosphorylation, CD40 and CD40L protein expression, and neutrophil adhesion
      onto ECs.

PMID- 16797504
TI  - Regulation of peripheral B cell maturation.
AB  - Although it is clear that the final phases of B cell maturation occur after newly
      formed B cells exit the bone marrow, the mechanisms underpinning the maturation,
      selection, and long-term survival of immature peripheral B cells remain poorly
      understood. Here, we review recent advances in our understanding of how B cell
      receptor (BCR)-mediated signaling events integrate with additional environmental
      cues to promote the selection and differentiation of immature B cells into
      functionally distinct subpopulations of mature B cells. We pay particular
      attention to the role of the Baff cytokine family and the Notch receptor-ligand
      family and their unique roles in promoting B cell survival and differentiation
      into follicular and marginal zone B cells.

PMID- 16797505
TI  - In utero exposure to alcohol alters cell fate decisions by hematopoietic
      progenitors in the bone marrow of offspring mice during neonatal development.
AB  - Fetal alcohol syndrome and alcohol related birth defects represent a spectrum of
      disorders that can result from the consumption of alcohol during pregnancy.
      Previous studies from this laboratory have shown that alcohol exposure in utero
      adversely affects hematopoietic progenitors in the bone marrow. Neonatal mice
      that were exposed in utero to alcohol showed a marked delay in B lymphocyte
      development. Recent studies have focused on an oligopotential progenitor cell,
      with the phenotype of HSA(lo)CD43(lo)Lin(-), which yields both B cells and
      myeloid lineage cells at a high frequency when cultured in vitro with stromal
      cells and the appropriate cytokines. However, these progenitor cells isolated
      from neonatal offspring of alcohol fed dams showed a significant decrease in the
      frequency of B cell formation following in vitro culture. In order to understand
      the mechanism underlying this defect we examined the expression of key
      transcription factors (early B cell factor, EBF, and Pax5) in this progenitor
      pool. Here, we report that >95% of HSA(lo)CD43(lo)Lin(-) cells express EBF and 5%
      express Pax5. Following liquid culture in the presence of IL-7, these progenitor
      cells respond by up-regulating Pax5 and the surface expression of CD19 indicating
      that the cells have committed to the B lineage. By contrast 75% of
      HSA(lo)CD43(lo)Lin(-) cells isolated from the bone marrow of neonatal animals
      exposed in utero to alcohol expressed EBF but at a level that was less than 25%
      the level of cells isolated from control animals. Furthermore, these alcohol
      exposed progenitor cells failed to up-regulate Pax5 in response to IL-7
      indicating a greatly reduced capacity to expand and differentiate to B lineage
      cells in liquid cultures. However, the HSA(lo)CD43(lo)Lin(-) cells isolated from
      the alcohol exposed animals retained the capacity to differentiate to myeloid
      lineage cells. These results suggest that the interference with the sequential
      expression of transcription factors in early progenitor cells by in utero alcohol
      exposure is a potential mechanism for the observed decrease in B lymphocytes in
      neonatal mice.

PMID- 16797506
TI  - Therapeutic effects of Semecarpus anacardium Linn. nut milk extract on the
      changes associated with collagen and glycosaminoglycan metabolism in adjuvant
      arthritic Wistar rats.
AB  - The effect of milk extract of Semecarpus anacardium Linn. nut milk extract (SA)
      was studied to gain some insight into this intriguing disease with reference to
      collagen metabolism. Arthritis was induced in rats by injecting Freund's complete
      adjuvant containing 10mg of heat killed mycobacterium tuberculosis in 1 ml
      paraffin oil (0.1 ml) into the left hind paw of the rat intradermally. After 14
      days of induction, SA (150 mg/kg body weight/day) was administered orally by
      gastric intubations for 14 days. Decreased levels of collagen and
      glycosaminoglycans (GAGS) components (chondroitin sulphate, heparan sulphate,
      hyaluronic acid) and increase in the levels of connective tissue degrading
      lysosomal glycohydrolases such as acid phosphatase, beta-glucuronidase, beta-N
      acetyl glucosaminidase and cathepsin-D observed in arthritic animals were
      reverted back to near normal levels upon treatment with SA. The drug effectively
      regulated the uriniray markers of collagen metabolism namely hexosamine,
      hexuronic acid, hydroxyproline and total GAGS. Electron microscopic studies also
      revealed the protective effect of SA. Hence, it can be suggested that SA very
      effectively regulate the collagen metabolism that derange during arthritic
      condition.

PMID- 16797507
TI  - Gastroprotective action of Cissus quadrangularis extract against NSAID induced
      gastric ulcer: role of proinflammatory cytokines and oxidative damage.
AB  - The objective of this research was to analyse the gastroprotective effect of
      Cissus quadrangularis extract (CQE) along with its mechanism underlying the
      therapeutic action against the gastric mucosal damage induced by aspirin. In this
      study, we investigated the effect of CQE on the course of experimentally induced
      gastric ulcer by analyzing the levels of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), microvascular permeability, activity of nitric
      oxide synthase-2 (NOS-2), mitochondrial antioxidants, lipid peroxidation and DNA
      damage. A significant increase in vascular permeability, NOS-2 activity, TNF
      alpha, IL-1beta levels and oxidative damage were noted in aspirin administered
      rats. Pretreatment with CQE (500 mg/kg bw/day) by oral gavage for 7 days
      significantly attenuated these biochemical changes caused by aspirin in rats.
      Tissue damage was showed by decreased levels of glutathione (GSH), superoxide
      dismutase (SOD) and catalase (CAT) and an associated rise in lipid peroxidation
      (LPO) in mitochondria, which were reversed by CQE. In addition, CQE prevents
      oxidative damage of DNA by reducing DNA fragmentation indicating its block on
      cell death. Ulcer protection in CQE treated rats was confirmed by
      histoarchitecture, which was comprised of reduced size of ulcer crater and
      restoration of mucosal epithelium. Thus, reduced neutrophil infiltration,
      antiapoptotic and antioxidant action have a pivotal role in the gastroprotective
      effect of CQE.

PMID- 16797508
TI  - Cyclophosphamide suppresses thioredoxin reductase in bladder tissue and its
      adaptive response via inductions of thioredoxin reductase and glutathione
      peroxidase.
AB  - Mammalian thioredoxin reductase (TrxR) catalyzes the reduction of oxidized
      thioredoxin in a NADPH-dependent manner, and contains a selenocysteine residue
      near the C-terminus. Glutathione peroxidase (GPx) is one of the primary
      antioxidant enzymes that scavenge hydrogen peroxide and organic hydroperoxides.
      Both TrxR and GPx play an important role in protecting against oxidative stress.
      Cyclophosphamide (CTX), one of the most widely prescribed antineoplastic drugs,
      could cause cystitis. We found that 4 h after a bolus dose of CTX (30, 90, 150,
      300 and 450 mg/kg) were administrated intraperitoneally, TrxR activity was
      significantly decreased in a dose-dependent manner, by 32%, 44%, 68%, 87% and
      99%, respectively, in comparison with control group. When fixing CTX dose at 150
      mg/kg, TrxR activity changed over time, significantly reduced to 68% of the
      activity in comparison with control tissue at 2 h, and gradually recovered to
      normal level within 24 h. In addition, we found that GPx activity was induced
      significantly after 4h. The results of the present study suggest that marked
      suppression of TrxR activity could be involved in the mechanism of CTX-induced
      cystitis, bladder may have a protective system against tissue damage by CTX via
      upregulation of TrxR and GPx, which is an adaptive response to oxidative stress.

PMID- 16797509
TI  - Mitochondrial involvement in genetically determined transition metal toxicity I.
      Iron toxicity.
AB  - Iron that is not specifically chaperoned through its essential functional
      pathways is damaging to biological systems, in major part by catalyzing the
      production of reactive oxygen species. Iron serves in several essential roles in
      the mitochondrion, as an essential cofactor for certain enzymes of electron
      transport, and through its involvement in the assembly of iron-sulfur clusters
      and iron-porphyrin (heme) complexes, both processes occurring in the
      mitochondrion. Therefore, there are mechanisms that deliver iron specifically to
      mitochondria, although these are not well understood. Under normal circumstances
      the mitochondrion has levels of stored iron that are higher than other
      organelles, though lower than in cytosol, while in some disorders of iron
      metabolism, mitochondrial iron levels exceed those in the cytosol. Under these
      circumstances of excess iron, protective mechanisms are overwhelmed and
      mitochondrial damage ensues. This may take the form of acute oxidative stress
      with structural damage and functional impairment, but also may result in long
      term damage to the mitochondrial genome. This review discusses the evidence that
      mitochondria do indeed accumulate iron in several genetic disorders, and are a
      direct target for iron toxicity when it is present in excess. We then consider
      two classes of genetic disorders involving iron and the mitochondrion. The first
      include defects in genes directly regulating mitochondrial iron metabolism that
      lead to Friedreich's ataxia and the various sideroblastic anemias, with excessive
      mitochondrial iron accumulation. Under the second class, we discuss various
      primary hemochromatoses that lead to direct mitochondrial damage, with reference
      to mutations in genes encoding HFE, hepcidin, hemojuvelin, transferrin receptor
      2, ferroportin, transferrin, and ceruloplasmin.

PMID- 16797510
TI  - Acetaminophen-induced hepatotoxicity of gel entrapped rat hepatocytes in hollow
      fibers.
AB  - An important application of primary hepatocyte cultures is for hepatotoxicity
      research. In this paper, gel entrapment culture of rat hepatocytes in
      miniaturized BAL system were evaluated as a potential in vitro model for
      hepatotoxicity studies in comparison to monolayer cultures. After exposure for 24
      and 48 h to acetaminophen (2.5 mM), gel entrapped hepatocytes were more severely
      damaged than hepatocyte monolayer detected by methyl thiazolyl tetrazolium (MTT)
      reduction, intracellular glutathione (GSH) content, reactive oxygen species (ROS)
      levels, urea genesis and albumin synthesis. CYP 2E1 activities detected by 4
      nitrocatechol (4-NC) formation were higher in gel entrapped hepatocytes than in
      hepatocyte monolayers while the addition of CYP 2E1 inhibitor, diethyl
      dithiocarbamate (DDC), more significantly reduced acetaminophen-induced toxicity
      in gel entrapped hepatocytes. In addition, protective effects of GSH, liquorice
      extract and glycyrrhizic acid against acetaminophen hepatotoxicity were clearly
      observed in gel entrapped hepatocytes but not in hepatocyte monolayer at an
      incubation time of 48 h. Overall, gel entrapped hepatocytes showed higher
      sensitivities to acetaminophen-induced hepatotoxicity than hepatocyte monolayer
      by a mechanism that higher CYP 2E1 activities of gel entrapped hepatocytes could
      induce more severe acetaminophen toxicity. This indicates that gel entrapped
      hepatocytes in hollow fiber system could be a promising model for toxicological
      study in vitro.

PMID- 16797511
TI  - Comparative analysis of cytotoxic, genotoxic and antioxidant effects of 2,2,4,7
      tetramethyl-1,2,3,4-tetrahydroquinoline and ethoxyquin on human lymphocytes.
AB  - 2,2,4,7-Tetramethyl-1,2,3,4-tetrahydroquinoline (THQ) is a new synthetic compound
      with potential antioxidant activity. In this study, cytotoxic, genotoxic and
      antioxidant activities of THQ were studied on human lymphocytes with the use of
      the trypan blue exclusion assay, the TUNEL method, the comet assay and the
      micronucleus test. The activities of THQ were compared with those of a
      structurally similar compound-ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4
      trimethylquinoline, EQ), which is used in animal feeds as a preservative.
      Cytotoxic effects of THQ were observed after 1-h treatment at the concentration
      of 500 microM and after 24-h treatments at the concentrations of 250-500 microM.
      Although the micronucleus test did not reveal a genotoxic effect of THQ, in the
      comet assay the statistically significant increase in DNA damage was observed as
      compared with the control. On the other hand, the protection of human lymphocytes
      against DNA damage induced by hydrogen peroxide suggests an antioxidant activity
      of THQ. The comparative analysis of THQ and EQ activities performed in these
      studies revealed that THQ was less cytotoxic and less genotoxic than EQ. Slightly
      lower antioxidant activity of THQ was also shown in the comet assay when it was
      used at the lower studied doses (1-5 microM), but for the highest one (10 microM)
      its efficiency was similar to that of EQ. In the micronucleus assay THQ was more
      effective than EQ in protecting the cultured lymphocytes from clastogenicity of
      H2O2. We believe that THQ is worthy of further detailed studies on its
      antioxidant properties to confirm its usefulness as a preservative.

PMID- 16797512
TI  - The "pro-apoptotic genies" get out of mitochondria: oxidative lipidomics and
      redox activity of cytochrome c/cardiolipin complexes.
AB  - One of the prominent consequences of the symbiogenic origin of eukaryotic cells
      is the unique presence of one particular class of phospholipids, cardiolipin
      (CL), in mitochondria. As the product originated from the evolution of symbiotic
      bacteria, CL is predominantly confined to the inner mitochondrial membrane in
      normally functioning cells. Recent findings identified CL and its oxidation
      products as important participants and signaling molecules in the apoptotic cell
      death program. Early in apoptosis, massive membrane translocations of CL take
      place resulting in its appearance in the outer mitochondrial membrane.
      Consequently, significant amounts of CL become available for the interactions
      with cyt c, one of the major proteins of the intermembrane space. Binding of CL
      with cytochrome c (cyt c) yields the cyt c/CL complex that acts as a potent CL
      specific peroxidase and generates CL hydroperoxides. In this review, we discuss
      the catalytic mechanisms of CL oxidation by the peroxidase activity of cyt c as
      well as the role of oxidized CL (CLox) in the release of pro-apoptotic factors
      from mitochondria into the cytosol. Potential implications of cyt c/CL peroxidase
      intracellular complexes in disease conditions (cancer, neurodegeneration) are
      also considered. The discovery of the new role of cyt c/CL complexes in early
      mitochondrial apoptosis offers interesting opportunities for new targets in drug
      discovery programs. Finally, exit of cyt c from damaged and/or dying (apoptotic)
      cells into extracellular compartments and its accumulation in biofluids is
      discussed in lieu of the formation of its peroxidase complexes with negatively
      charged lipids and their significance in the development of systemic oxidative
      stress in circulation.

PMID- 16797513
TI  - Effect of cholesterol on lateral diffusion of fluorescent lipid probes in native
      hippocampal membranes.
AB  - Cholesterol is an abundant lipid of mammalian membranes and plays a crucial role
      in membrane organization, dynamics, function and sorting. The role of cholesterol
      in membrane organization has been a subject of intense investigation that has
      largely been carried out in model membrane systems. An extension of these studies
      in natural membranes, more importantly in neuronal membranes, is important to
      establish a relationship between disease states and changes in membrane physical
      properties resulting from an alteration in lipid composition. We have monitored
      the lateral diffusion of lipid probes, DiIC(18)(3) and FAST DiI which are similar
      in their intrinsic fluorescence properties but differ in their structure, in
      native and cholesterol-depleted hippocampal membranes using the fluorescence
      recovery after photobleaching (FRAP) approach. Our results show that the mobility
      of these probes is in general higher in hippocampal membranes depleted of
      cholesterol. Interestingly, the increase in mobility of these probes does not
      linearly correlate with the extent of cholesterol depletion. These results assume
      significance in the light of recent reports on the requirement of cholesterol to
      support the function of the G-protein coupled serotonin(1A) receptor present
      endogenously in hippocampal membranes.

PMID- 16797514
TI  - Biologic markers of mortality in acute lung injury.
AB  - Acute lung injury (ALI) is a clinical syndrome in which patients develop severe
      and progressive pulmonary gas exchange defects and pulmonary mechanical
      dysfunction. The high morbidity and mortality (40%) associated with ALI provide a
      compelling need to identify clinical and/or biochemical parameters that robustly
      risk stratify patients for both accurate prognostication and clinical trial
      purposes. In this review, we will examine and critically evaluate studies
      pertaining to biochemical markers of mortality in ALI. These markers may not only
      serve as prognostic measures of disease, but in some cases, add to our overall
      understanding of the pathophysiology of ALI.

PMID- 16797516
TI  - Association between paraoxonase activity and lipid levels in patients with
      premature coronary artery disease.
AB  - BACKGROUND: South Asians, especially Indians show increased risk for
      atherosclerosis and have the higher mortality rates due to coronary artery
      disease. The increasing incidence of coronary artery disease in young patients is
      possibly due to industrialization, stress of life, less exercise and increasing
      incidence of smoking and other factors. We attempted to determine an independent
      association of paraoxonase with coronary artery disease in young patients.
      METHOD: The lipid profile and serum paraoxonase were investigated in 120
      angiographically-proven premature coronary artery disease patients (99 males and
      21 females, all <45 years) with diabetes mellitus, smoking, hyperlipidemia,
      obesity, hypertension along with 50 (41 male and 9 female) normal subjects and
      compared. RESULTS: A significant increase was observed in the concentrations of
      total cholesterol, triglycerides and LDL cholesterol in premature coronary artery
      disease patients. The activities of paraoxonase and HDL cholesterol
      concentrations decreased in coronary artery disease patients compared to control
      subjects. CONCLUSION: A paraoxonase was an independent (p<0.001, OR 14.9 and 95%
      CI 5.6-35.9) risk factor for premature coronary artery disease patients along
      with lipid profiles. Paraoxonase activity should be evaluated in all coronary
      artery disease patients in the absence of traditional risk factors.

PMID- 16797517
TI  - Evaluation of two fully automated novel enzyme-linked immunosorbent assays for
      the determination of human adiponectin in serum.
AB  - BACKGROUND: In contrast to RIA, recently available ELISAs provide the potential
      for fully automated analysis of adiponectin. To date, studies reporting on the
      diagnostic characteristics of ELISAs and investigating on the relationship
      between ELISA- and RIA-based methods are rare. METHODS: Thus, we established and
      evaluated a fully automated platform (BEP 2000; Dade-Behring, Switzerland) for
      determination of adiponectin levels in serum by two different ELISA methods
      (competitive human adiponectin ELISA; high sensitivity human adiponectin sandwich
      ELISA; both Biovendor, Czech Republic). Further, as a reference method, we also
      employed a human adiponectin RIA (Linco Research, USA). Samples from 150 patients
      routinely presenting to our cardiology unit were tested. RESULTS: ELISA
      measurements could be accomplished in less than 3 h, measurement of RIA had a
      duration of 24 h. The ELISAs were evaluated for precision, analytical sensitivity
      and specificity, linearity on dilution and spiking recovery. In the investigated
      patients, type 2 diabetes, higher age and male gender were significantly
      associated with lower serum adiponectin concentrations. Correlations between the
      ELISA methods and the RIA were strong (competitive ELISA, r=0.82; sandwich ELISA,
      r=0.92; both p<0.001). However, Deming regression and Bland-Altman analysis
      indicated lack of agreement of the 3 methods preventing direct comparison of
      results. The equations of the regression lines are: Competitive ELISA=1.48 x RIA
      0.88; High sensitivity sandwich ELISA=0.77 x RIA+1.01. CONCLUSIONS: Fully
      automated measurement of adiponectin by ELISA is feasible and substantially more
      rapid than RIA. The investigated ELISA test systems seem to exhibit analytical
      characteristics allowing for clinical application. In addition, there is a strong
      correlation between the ELISA methods and RIA. These findings might promote a
      more widespread use of adiponectin measurements in clinical research.

PMID- 16797518
TI  - New high mobility group box 1 assay system.
AB  - BACKGROUND: High-sensitivity sandwich ELISA methods have been developed using
      chemiluminescent substrates. HMGB1 (high mobility group box 1) protein has been
      shown to play a critical role in several inflammatory diseases and it may be
      involved in the development of atherosclerosis. METHODS: Anti-human HMGB1
      monoclonal antibodies and anti-peptide polyclonal antibodies against the peptide
      sequence (KPDAAKKGVVKAEK) with high antigenicity and different from the sequence
      of HMGB2 were developed, and the antibodies were used to construct sandwich ELISA
      methods with a chromogenic substrate (TMBZ) and a chemiluminescent substrate (PS
      atto). Highly purified human HMGB1 was used as a standard material and high
      sensitivity CRP was measured to compare with HMGB1. RESULTS: The analytical
      characteristics of the ELISA method we developed were validated inter-assay and
      intra-assay CVs were <10%, and the detection limit was 0.3 microg/l by the
      chemiluminescent method and 1 microg/l with the chromogenic substrates. HMGB1 was
      detected in the serum of patients with acute coronary syndrome (ACS). When a cut
      off of 0.6 microg/l HMGB1 upon admission to the intensive care unit (ICU) was
      used, the risk of developing an acute cardiac event within 1 month after
      discharge of ACS patients with an abnormal HMGB1 was significantly higher than
      for the patients with normal values (P<0.0001). The usefulness of HMGB1 as an
      acute prognostic marker was suggested. CONCLUSIONS: The assay is easy to perform
      and suitable for use in the hospital laboratory and for screening large
      populations. HMGB1 is detectable in the serum of ACS patients and that the serum
      concentration of HMGB1 may be a prognostic indicator in ACS patients.

PMID- 16797519
TI  - Influence of hematocrit and localisation of punch in dried blood spots on levels
      of amino acids and acylcarnitines measured by tandem mass spectrometry.
AB  - BACKGROUND: Detection of amino acids (AA), acylcarnitines (AC), and
      guanidinoacetate (GAA) in dried blood spots by tandem mass spectrometry has made
      it possible to detect different inborn errors of metabolism in neonatal screening
      programs. Despite its proven sensitivity many issues related to sample
      preparation remain unsolved. Hematocrit has a profound effect on blood viscosity,
      and may thereby influence flux and diffusion properties of the blood. As newborn
      infants show a considerable interindividual variability of hematocrit levels, we
      investigated its effect on levels of AA and AC in dried blood spots. METHODS:
      Blood samples with defined hematocrit levels (20%, 30%, 40%, 50%, 60%) were
      produced by diluting blood cells with plasma from a single donor. Forty dried
      blood spots were made for each hematocrit level and a central as well as a
      peripheral 3 mm disk was punched and analysed for AA, AC, and GAA, respectively.
      RESULTS: Levels of most AA and GAA increased significantly with increasing
      hematocrit (p<0.001), while the effect of hematocrit on some AA was less
      pronounced. Total AC, free carnitine, some long, medium and short chain AC
      correlated positively with hematocrit levels (p<0.001). In samples with low
      hematocrit, levels of most AA and free carnitine were higher in the peripheral
      than in the central disk (p<0.0001). CONCLUSIONS: Both hematocrit and position of
      the disk within the dried blood spot have a significant and sometimes additive
      effect on levels of AA, AC and GAA in dried blood spots. Theoretically, diagnoses
      may be missed depending on hematocrit and position of the disk.

PMID- 16797520
TI  - Comment on 'Effect of atorvastatin on SR-BI expression and HDL-induced
      cholesterol efflux in adipocytes of hypercholesterolemic rabbits' by Zhao et al.
      (Clin Chim Acta 2006; 365: 119-24).

PMID- 16797521
TI  - The role of amylin and related peptides in osteoporosis.
AB  - Osteoporosis is a systemic skeletal disorder that remains a major public health
      problem due to significant fracture-associated morbidity and mortality. Because
      it has been shown that individuals having type I diabetes mellitus also suffer
      from osteopenia or osteoporosis, there is probably a pathophysiological mechanism
      that links pancreatic beta cell insufficiency with inappropriate bone formation.
      Many factors have been suggested, including amylin, a product of pancreatic beta
      cells with structural and functional similarity to calcitonin. Amylin has been
      shown to stimulate bone development via action on osteoblasts and osteoclasts.
      Recently, amylin receptors have been identified as complexed calcitonin receptor
      with receptor activity modifying proteins. Moreover, a synthetic amylin analogue
      (pramlintide) has been developed for clinical use. These findings including
      results from in vitro animal and human studies suggest a role for amylin as a
      potential diagnostic and therapeutical tool in patients with various bone
      diseases including osteoporosis. However, other structurally and functionally
      related hormones that affect bone metabolism should also be taken in account
      including calcitonin, calcitonin gene-related peptide and adrenomedullin.

PMID- 16797522
TI  - Viewpoint costs occur during consolidation: evidence from the attentional blink.
AB  - Do the viewpoint costs incurred when naming rotated familiar objects arise during
      initial identification or during consolidation? To answer this question we
      employed an attentional blink (AB) task where two target objects appeared amongst
      a rapid stream of distractor objects. Our assumption was that while both targets
      and distractors undergo initial identification only targets are consolidated in a
      form that allows overt report. We presented line drawings of objects with a usual
      upright canonical orientation, and separately manipulated the orientation of
      targets and distractors. In two experiments, targets were defined by colour,
      whereas in a third experiment they were defined by semantic category. Target 1
      orientation influenced the AB, with objects rotated by 90 degrees causing a
      larger second target deficit than upright and upside-down objects. However,
      distractor orientation did not affect the magnitude of the second target deficit,
      regardless of whether targets were defined by colour or semantic category. Taken
      together, these findings suggest that the visual representations involved in the
      preliminary recognition of familiar objects are viewpoint-invariant and that
      viewpoint costs are incurred when these objects are consolidated for report.

PMID- 16797523
TI  - Why aren't identical twins linguistically identical? Genetic, prenatal and
      postnatal factors.
AB  - Results of twin studies clearly demonstrate that genetic factors play an
      important role in the rate of language acquisition and linguistic proficiency
      attained by normal and impaired children and adults [see Stromswold, K. (2001).
      The heritability of language: A review and meta-analysis of twin, adoption and
      linkage studies. Language, 77, 647-723.]. That said, twin-based heritability
      estimates for language rarely exceed .6 and monozygotic (MZ) twins (who are
      usually assumed to have identical genetic and environmental endowments) sometimes
      have very different linguistic profiles. In addition, twins are more likely to
      suffer linguistic delays and impairments than singletons. Postnatal factors, such
      as differences in linguistic input twins receive, are usually assumed to be the
      major reason for these findings. This paper discusses how genetic, epigenetic,
      and perinatal environmental factors can lower heritability estimates for
      language, cause MZ twins to be linguistically discordant, and increase the risk
      of language impairments in twins. We present results from our ongoing Perinatal
      Environment and Genetic Interaction (PEGI) study that suggest that perinatal
      environmental factors affect linguistic development more than postnatal factors,
      and that postnatal factors affect cognitive development more than perinatal
      factors. Because perinatal factors are overwhelming biological, whereas postnatal
      factors tend to be psychosocial (e.g., how and how much parents speak to their
      children), these results support nativist/biological theories of language and
      language development and call into question empiricist/emergentist theories.
      These results are also consistent with modularist theories of language. We end by
      suggesting new methods that can be used to tease apart the effects of prenatal
      and postnatal environment and to investigate how these factors interact with
      genetic factors.

PMID- 16797524
TI  - Phonological and conceptual activation in speech comprehension.
AB  - We propose that speech comprehension involves the activation of token
      representations of the phonological forms of current lexical hypotheses,
      separately from the ongoing construction of a conceptual interpretation of the
      current utterance. In a series of cross-modal priming experiments, facilitation
      of lexical decision responses to visual target words (e.g., time) was found for
      targets that were semantic associates of auditory prime words (e.g., date) when
      the primes were isolated words, but not when the same primes appeared in sentence
      contexts. Identity priming (e.g., faster lexical decisions to visual date after
      spoken date than after an unrelated prime) appeared, however, both with isolated
      primes and with primes in prosodically neutral sentences. Associative priming in
      sentence contexts only emerged when sentence prosody involved contrastive
      accents, or when sentences were terminated immediately after the prime.
      Associative priming is therefore not an automatic consequence of speech
      processing. In no experiment was there associative priming from embedded words
      (e.g., sedate-time), but there was inhibitory identity priming (e.g., sedate
      date) from embedded primes in sentence contexts. Speech comprehension therefore
      appears to involve separate distinct activation both of token phonological word
      representations and of conceptual word representations. Furthermore, both of
      these types of representation are distinct from the long-term memory
      representations of word form and meaning.

PMID- 16797525
TI  - Expression of aquaporin-3 improves the permeability to water and cryoprotectants
      of immature oocytes in the medaka (Oryzias latipes).
AB  - The permeability of the plasma membrane plays a crucial role in the successful
      cryopreservation of oocytes and embryos. Several efforts have been made to
      facilitate the movement of water and cryoprotectants across the plasma membrane
      of fish oocytes/embryos because of their large size. Aquaporin-3 is a
      water/solute channel that can also transport various cryoprotectants. In this
      study, we tried to improve the permeability of immature medaka (Oryzias latipes)
      oocytes to water and cryoprotectants by artificially expressing aquaporin-3. The
      oocytes were injected with aquaporin-3 cRNA and cultured for 6-7 h. Then,
      hydraulic conductivity (L(P)) and cryoprotectant permeability (P(S)) were
      determined from volume changes in a hypertonic sucrose solution and various
      cryoprotectant solutions, respectively, at 25 degrees C. The L(P) value of the
      cRNA-injected oocytes was 0.22+/-0.04 microm/min/atm, nearly twice larger than
      that of intact or water-injected oocytes (0.14+/-0.02 and 0.14+/-0.03
      microm/min/atm, respectively). P(S) values of intact oocytes for ethylene glycol,
      propylene glycol, and DMSO were 1.36+/-0.34, 1.97+/-0.20, and 1.17+/-0.52 x 10(
      3) cm/min, respectively. The permeability to glycerol could not be calculated
      because oocytes remained shrunken in the glycerol solution. On the other hand,
      cRNA-injected oocytes had significantly higher P(S) values (glycerol, 2.20+/
      1.29; ethylene glycol, 2.98+/-0.36; propylene glycol, 3.93+/-1.70; DMSO, 3.11+/
      0.74 x 10(-3) cm/min) than intact oocytes. When cRNA-injected oocytes were
      cultured for 12-14 h, 51% matured to the metaphase II stage, and 43% of the
      matured oocytes were fertilized and hatched following in vitro fertilization and
      14 days of culture. Thus, the permeability of medaka oocytes to water and
      cryoprotectants was improved by the artificial expression of aquaporin-3, and the
      oocytes retained the ability to develop to term.

PMID- 16797526
TI  - Cbf beta regulates Runx2 function isoform-dependently in postnatal bone
      development.
AB  - Runx2 and Cbfbeta are essential for skeletal development during the embryonic
      stage. Runx2 has two isoforms with different N-termini. We examined the functions
      of the Runx2 isoforms and Cbfbeta in postnatal bone development. On luciferase
      and electrophoretic mobility shift assays, Runx2-I was less active than Runx2-II
      in the absence of Cbfb, but the two Runx2 isoforms had similar activity levels in
      the presence of Cbfb. We generated Runx2-I transgenic mice under the control of
      Col1a1 promoter and Runx2-I/Cbfb and Runx2-II/Cbfb double transgenic mice. Runx2
      I transgenic mice showed less severe osteopenia and fragility than Runx2-II
      transgenic mice due to milder inhibition of both osteoblast maturation and
      transition to osteocytes, even though the former mice showed higher transgene
      expression. However, Runx2-I/Cbfb and Runx2-II/Cbfb double transgenic mice had
      enhanced inhibition of osteoblast maturation, resulting in similar severity of
      osteopenia and fragility, although the latter mice had less osteocytes. These
      findings indicate that (1) Runx2-II more strongly inhibits osteoblast maturation
      and transition to osteocytes than Runx2-I; (2) Cbfbeta regulates Runx2 function
      isoform-dependently; and (3) Runx2-I activity is highly dependent on Cbfbeta.
      These findings demonstrate that Runx2 isoforms exert their functions through at
      least partly different mechanisms and Cbfbeta regulates bone development by
      regulating Runx2 function isoform-dependently.

PMID- 16797528
TI  - STAT4 and the proliferation of artery smooth muscle cells in atherosclerosis.
AB  - Artery smooth muscle cell proliferation is of key importance in the development
      of atherosclerosis and restenosis following PTCA. In order to understand gene
      regulation involved in these processes, vascular smooth muscle cells (VSMCs) from
      atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show
      Racer (SR) pigeons were used to identify transcription factors involved in the
      enhanced proliferation of WC VSMCs. With protein/DNA array, signal transducer and
      activator of transcription 4 (STAT4) was found to have over a 10-fold increase in
      expression in WC compared to SR VSMCs. The difference was confirmed with
      electrophoretic-mobility shift assay (EMSA) and Western blot. Cells cultured
      under low serum had 5-fold higher levels of STAT4 in WC compared to SR. By
      Western analysis, aortic tissue from newly hatched WC pigeons had 1.7-2.0 times
      greater STAT4 expression than in SR pigeons. A pathway whereby enhanced STAT4 may
      be associated with enhanced proliferation was identified following IL-12
      stimulation of WC VSMCs where 3-fold increases in proliferation and 2-fold higher
      expression of STAT4 were measured. The findings suggest STAT4 may play a role in
      VSMC proliferation and describe a unique pigeon model system in which to study
      STAT4 as a gene target for atherosclerosis therapy.

PMID- 16797527
TI  - Anti-oxidant sensitivity of donor age-related gene expression in cultured
      fibroblasts.
AB  - Cultured human fibroblasts display age-dependent transcriptomic differences. We
      hypothesized that aging-associated oxidative stress affects gene expression, and
      monitored the transcriptome in confluent fibroblasts from young and old
      individuals cultured without and with a lipophilic and hydrophilic anti-oxidant
      mixture (vitamin E, quercetin, hydroxytyrosol and kaempferol). In cells derived
      from old subjects genes with lower expression were related to oxidative stress,
      growth and differentiation, cell cycle or metabolic enzymes and with higher
      expression to protein processing and docking, extracellular matrix, immune
      response, EGF-signalling and transcription. Anti-oxidant treatment modulated a
      similar number of genes in all donors and induced cell cycle regulatory genes. A
      subset of genes, modulated by age and inversely modulated by anti-oxidants,
      included glutaminase. Despite increased glutaminase expression, donor age
      dependent decline in glutathione content and resistance to glutathione-depletion
      was observed. Summarizing, gene expression of fibroblasts is affected by donor
      age and a subset was corrected by anti-oxidants. Thus, in cultured fibroblasts
      from aged donors, gene expression is partly driven by oxidative stress.

PMID- 16797529
TI  - Hypertrophic response of Duchenne and limb-girdle muscular dystrophies is
      associated with activation of Akt pathway.
AB  - Dystrophic muscle undergoes repeated cycles of degeneration/regeneration,
      characterized by the presence of hypertrophic fibers. In order to elucidate the
      signaling pathways that govern these events, we investigated Akt activation in
      normal and dystrophic muscle. Akt is activated in neonatal muscle and in actively
      dividing myoblasts, supporting a developmental role for Akt signaling. Akt
      activation was detected at very early, prenecrotic stages of disease
      pathogenesis, and maximal activation was observed during peak stages of muscle
      hypertrophy. Duchenne muscular dystrophy patients exhibit a similar pattern of
      Akt activation. Mice with sarcoglycan-deficient muscular dystrophy possess more
      severe muscle pathology and display elevated Akt signaling. However, the highest
      levels of Akt activation were found in dystrophin-utrophin-deficient muscle with
      very advanced dystrophy. We propose that Akt may serve as an early biomarker of
      disease and that Akt activation mediates hypertrophy in muscular dystrophy.
      Current investigations are focused on introducing constitutively active and
      dominant-negative Akt into prenecrotic mdx mice to determine how early
      modification of Akt activity influences disease pathogenesis.

PMID- 16797530
TI  - Dissecting the sequence specific functions of alternative N-terminal isoforms of
      mouse bullous pemphigoid antigen 1.
AB  - Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family of proteins
      that is involved in cross-linking the cytoskeletal elements and attaching them to
      cell junctions. BPAG1 null mice develop severe degeneration of sensory neurons
      that was attributed in part due to the absence of a splice variant called BPAG1a
      that harbors an actin-binding domain at the N-terminus. Additional alternative
      splicing also results in BPAG1a isoforms with different first exons, leading to
      three additional types of BPAG1a called isoforms 1, 2 and 3 (or BPAG1a1, BPAG1a2,
      and BPAG1a3). These unique N-terminal extensions of the BPAG1a isoforms are of
      variable length. In this study, we characterized these N-terminal isoforms and
      evaluated the influence of these unique N-terminal sequences to the actin-binding
      properties. The unique N-terminal region of isoform 1 is very short and was not
      expected to affect the property of the ABD that followed it. In contrast,
      transfection studies and mutagenesis analyses signified that the N-terminal
      sequences of isoform 2 had the ability to bundle actin filaments and the N
      terminal region that contained isoform 3 showed cortical localization. Isoforms
      1, 2 and 3 also displayed differential tissue expression profiles. Taken
      together, these data suggested that the unique N-terminal regions of these
      isoforms have different roles that may be tailored to meet tissue specific
      functions.

PMID- 16797531
TI  - Acute effects of dietary retinoic acid on ocular components in the growing chick.
AB  - When the eyes of chicks are induced to grow toward myopia or hyperopia by having
      them wear spectacle lenses or diffusers, opposite changes take place in the
      retina and choroid in the synthesis and levels of all-trans Retinoic Acid (RA).
      To explore whether RA plays a causal role in the regulation of eye growth, we fed
      young chicks RA (doses 0.5 to 24 mg/kg) either twice a day or on alternate days
      or only once. Refractive error was measured with a Hartinger refractometer;
      ocular length, lens-thickness and choroidal thickness were measured by A-scan
      ultrasound. The amount of RA present in ocular tissues was determined using HPLC.
      Oral delivery of RA effectively increased RA in ocular tissues within 8h. During
      the first day after feeding RA at levels above 8 mg/kg, the rate of ocular
      elongation tripled, the choroid thickened and lens thickening was inhibited. The
      day following a dose of RA, the rate of ocular elongation was inhibited and the
      lens thickened more than normal. Nonetheless, the cumulative effect of repeated
      doses was that the eye became longer and the lens became thinner than normal,
      with no net change in refractive error. The rate of elongation was also increased
      by feeding 13-cis RA, and was reduced by citral, an inhibitor of RA synthesis.
      Surprisingly, birds fed RA while being kept in darkness also had normal
      refractive errors despite increased ocular elongation, and birds wearing either
      +6D or -6D spectacle lenses compensated normally for the lenses despite the
      enhanced ocular elongation caused by the RA. These results suggest that RA may
      act at the level of a coordinated non-visual regulatory system which controls the
      growth of the various ocular components, arguing that emmetropization does not
      depend entirely on vision.

PMID- 16797532
TI  - Induced expression of hematopoietic- and neurologic-expressed sequence 1 in
      retinal pigment epithelial cells during newt retina regeneration.
AB  - Newts can regenerate their organs even as adults. For instance, when their neural
      retinas are completely removed by operation, the remaining retinal pigment
      epithelial (RPE) cells dedifferentiate to reconstruct neural retinas. To
      elucidate the molecular mechanisms of newt retina regeneration, we investigated
      genes upregulated in dedifferentiating RPE cells using differential display
      methods. We observed that a cDNA fragment of hematopoietic- and neurologic
      expressed sequence 1 (Hn1) appeared to be induced within a few days of surgical
      removal of newt neural retina. Using an anti-HN1 antiserum against the
      recombinant HN1 protein, we carried out immunohistochemical analyses. The anti
      HN1 antiserum recognized the plexiform layers and ganglion cell layer (GCL) but
      not the RPE cell layer in unoperated (normal) newt retinas. Using a glial
      fibrillary acidic protein antibody, Hn1 was shown to be possibly expressed in
      glial cells in normal neural retina. During retina regeneration, immunoreactivity
      for HN1 appeared in dedifferentiating RPE cells 10 days post-operation, and in
      retinal progenitor cells 18 days post-operation. Twenty seven days post
      operation, HN1 immunoreactivity was localized in the plexiform layers and GCL as
      in the normal retina. Therefore, HN1 possibly plays an undefined role in
      dedifferentiating RPE cells and retinal progenitor cells during newt retina
      regeneration.

PMID- 16797533
TI  - Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract
      formation through modulation of Na,K-ATPase activity and osmotic stress.
AB  - Phospholipase D (PLD), a highly regulated enzyme that generates the second
      messenger phosphatidic acid, functions in signal transduction, membrane
      trafficking and cytoskeletal reorganization. PLD is thought to be involved in the
      pathogenesis of diabetic complications by activating PKC. Since PKC and PLD are
      present in the lens we sought to determine if PLD plays a role in diabetic
      cataract development. We developed transgenic mice that overexpress PLD2, one of
      the two mammalian isoforms of PLD. These mice developed congenital nuclear
      cataracts, but not diabetic cataracts. Histological analysis revealed vacuole
      formation in the fiber cells, mediated potentially by the substantially increased
      Na,K-ATPase activity. In the presence of the aldose reductase overexpressing
      transgene that increases lens osmotic pressure, these double transgenic mice
      developed more severe congenital cataract and became susceptible to develop
      diabetic cataract. Together, these data suggest that increased PLD2 activity in
      the lens under hyperglycemic condition might impair its osmoregulatory mechanism
      and reduce its ability to cope with the osmotic stress triggered by sorbitol
      accumulation.

PMID- 16797534
TI  - Cyclic AMP-mediated regulation of the resting membrane potential in myelin
      forming oligodendrocytes in the isolated intact rat optic nerve.
AB  - Myelin formation by oligodendrocytes has been shown to be regulated by cyclic AMP
      (cAMP) signaling pathways and to depend on the resting membrane potential (RMP).
      We therefore examined whether cAMP regulates the RMP of myelin-forming
      oligodendrocytes in isolated intact optic nerves of rats. Oligodendrocytes
      exhibited a significant developmental shift in the RMP from -37 mV at postnatal
      day (P)6-8 to -67 mV at P21-30. The regulation of RMP was examined further in
      myelin-forming oligodendrocytes in nerves aged P15-20. Raising intracellular cAMP
      with dbcAMP or forskolin induced a significant hyperpolarization in myelin
      forming oligodendrocytes by 10-15 mV. Inhibition of cAMP-dependent protein kinase
      (PKA) with KT5720 depolarized the oligodendroglial RMP -30 mV, which was only
      partly reversed by dbcAMP. In contrast, inhibition of cAMP specific
      phosphodiesterase with rolipram had no significant effect on the oligodendroglial
      RMP or the cAMP-mediated hyperpolarization. Blockade of Kir with 100 microM
      BaCl(2) depolarized the oligodendrocyte RMP to -25 mV and inhibited the
      hyperpolarizing action of dbcAMP. The RMP was unaffected by agents that modulated
      ATP-sensitive potassium channels. The results provide evidence of a predominant
      role for Kir in setting the oligodendroglial RMP and show that cAMP regulates the
      oligodendroglial RMP, at least partly by a PKA-mediated pathway, possibly by
      modulating the activity of Kir.

PMID- 16797535
TI  - Females remyelinate more efficiently than males following demyelination in the
      aged but not young adult CNS.
AB  - To assess the effects of sex on CNS remyelination, demyelinating lesions were
      induced by injection of ethidium bromide into the caudal cerebellar peduncle of
      Sprague-Dawley rats divided into the following 8 groups: young adult male, young
      adult female, old adult male and old adult female and each of these in which the
      gonads had been removed 4 weeks prior to lesion induction. Remyelination was
      assessed, blinded to grouping, by a ranking analysis using standard morphological
      criteria. In young adult animals, where remyelination proceeds rapidly, there was
      no difference in the remyelination at four weeks after lesion induction in male
      or females regardless of whether they were intact or castrated/ovariectomised.
      However, in old adult rats, where remyelination proceeds slowly, the extent of
      oligodendrocyte remyelination was significantly less in males compared to females
      at 8 weeks after lesion induction. Removal of gonads did not affect remyelination
      in old rats of either gender. These results indicate a sex-associated divergence
      in remyelination efficiency that occurs with ageing that is unaffected by the
      removal of gonadal sources of sex steroid hormones.

PMID- 16797536
TI  - Contralesional neural plasticity and functional changes in the less-affected
      forelimb after large and small cortical infarcts in rats.
AB  - Some studies have found that unilateral cerebral damage produces significant
      deficits in the ipsilesional, "less-affected", body side. Other studies have
      found that such damage results in a paradoxical hyperfunctionality of the
      ipsilesional body side and a facilitation of learning-induced neuroplastic
      changes in the contralesional motor cortex. The purpose of this study was to
      determine whether these effects co-exist and/or vary with lesion severity. After
      small or large unilateral ischemic lesions of the sensorimotor cortex (SMC) or
      sham operations, adult male rats were trained for 20 days to acquire a motor
      task, skilled reaching for food, for the first time with the ipsilesional
      forelimb. Analyses of movement patterns indicated lesion-size-dependent
      ipsilesional abnormalities in grasping, retrieving and releasing food pellets.
      Despite these impairments, success rates were significantly increased and aiming
      errors reduced in lesion groups compared with sham operates. Performance was best
      in rats with small lesions that had more minor ipsilesional impairments. In the
      motor cortex contralateral to the lesion and trained limb, there were significant
      increases in the density of dendrites immunoreactive for microtubule-associated
      protein-2 (MAP2) and of N-methyl-D-aspartate receptor subunit 1 (NMDAR1)
      immunoreactivity compared with sham operates. These effects were correlated with
      reaching performance. Therefore, enhanced motor skill learning in the "less
      affected" forelimb and contralesional neuroplastic changes are muted after larger
      lesions and co-exist with ipsilesional impairments. These effects may be related
      to a denervation-induced neural restructuring of the contralesional cortex that
      both disrupts pre-existing motor engrams and facilitates the establishment of new
      ones.

PMID- 16797537
TI  - Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of
      epidermal innervation and activation of Langerhans cells.
AB  - Experimental painful peripheral neuropathies produced by the chemotherapeutic
      drugs, paclitaxel and vincristine, are produced by relatively low doses that do
      not cause axonal degeneration in peripheral nerve. Using quantitative
      immunolabeling with the PGP9.5 antibody, we have investigated whether these
      painful neuropathies might be associated with degeneration that is confined to
      the region of the sensory fiber's receptor terminals in the skin. Because
      complete and partial nerve transections are known to cause an increase in PGP9.5
      in epidermal Langerhans cells (LCs), we also examined whether this effect occurs
      in chemotherapy-treated animals. At the time of peak pain severity, rats with
      paclitaxel- and vincristine-evoked painful peripheral neuropathies had a
      significant decrease (24% and 44%, respectively) in the number of intraepidermal
      nerve fibers (IENF) in the hind paw glabrous skin and an increase (217% and 121%,
      respectively) in the number of PGP9.5-positive LCs, relative to control. However,
      neither loss of IENF nor an increase in PGP9.5-positive LCs was found in rats
      with a painful peripheral neuropathy evoked by the anti-HIV agent, 2',3'
      dideoxycytidine. We also confirmed that there is a decrease in IENF and an
      increase in PGP9.5-positive LCs in rats with neuropathic pain following a partial
      nerve injury (CCI model) and in rats with a complete sciatic nerve transection.
      Partial degeneration of the intraepidermal innervation suggests mechanisms that
      might produce chemotherapy-evoked neuropathic pain, and activation of cutaneous
      LCs suggests possible neuroimmune interactions that might also have a role.

PMID- 16797538
TI  - Tapered progesterone withdrawal promotes long-term recovery following brain
      trauma.
AB  - We previously demonstrated that after traumatic brain injury (TBI), acute
      progesterone withdrawal (AW) causes an increase in anxiety behaviors and cerebro
      cellular inflammation compared to tapered progesterone withdrawal (TW). Our
      current study investigates the behavioral and cellular effects of AW two weeks
      after termination of treatments to determine the longer-term influence of
      withdrawal after injury. Adult, male Sprague-Dawley rats received either
      bilateral frontal cortex contusion (L) or sham (S) surgery. Rats were injected at
      1 and 6 h post-injury, then every 24 h for six days. Vehicle (V)-treated rats
      were given 9 injections of 22.5% cyclodextrin, whereas AW rats received 9
      injections of 16 mg/kg progesterone and TW rats received 7 injections of P at 16
      mg/kg, followed by one at 8 mg/kg and one at 4 mg/kg. On day 8, sensory neglect
      and locomotor activity tests were initiated. Animals were killed 22 days post-TBI
      and the brains prepared for either molecular or histological analysis. Western
      blotting revealed increased brain-derived neurotrophic factor (BDNF) and heat
      shock protein 70 (HSP70) in TW vs. AW animals. P53 was increased in VL animals,
      whereas all progesterone-treated groups were equivalent to shams. TW animals had
      markedly decreased sensory neglect compared to AW animals and increased center
      time in locomotor activity assays. In addition, lesion reconstruction revealed a
      decreased lesion size for TWL over AWL over VL animals. Glial fibrillary acidic
      protein (GFAP) immunofluorescent staining followed this pattern as well. In
      conclusion, after TBI, AW affects select behaviors and molecular markers in the
      chronic recovery period.

PMID- 16797539
TI  - Magnetically evoked inter-enlargement response: an assessment of ascending
      propriospinal fibers following spinal cord injury.
AB  - The aim of the present study was to characterize a novel electrophysiological
      assessment, the magnetically evoked interenlargement response (MIER), by defining
      the anatomical location of the fast conducting (large myelinated) ascending axons
      that mediate the response and the relationship between the response and locomotor
      function following experimental spinal cord injury. Electromyographic (EMG)
      responses were recorded from the triceps muscles following magnetic stimulation
      of one hip. Short-latency (approximately 6 ms) EMGs were recorded from triceps
      muscles in normal controls and following different laceration injuries (dorsal,
      lateral or dorsal and lateral hemisections) or a 150-kilodyne (kd) contusion
      injury at the T9 level. The amplitude of the triceps MIER was significantly
      correlated to the area of spared white matter in the lateral funiculus and to
      hindlimb function during open field locomotion (r2 = 0.55). Following a complete
      lateral hemisection, MIERs were present in the triceps bilaterally following
      stimulation of either hip. Responses could also be recorded from the masseter
      muscles indicating that the influence of this pathway extends beyond the spinal
      cord. Anatomical evidence of a bilaterally distributed propriospinal pathway was
      found when biotinylated dextran amine (BDA) was injected into the lateral white
      matter on one side of the spinal cord at T9. BDA-labeled axons with varicosities
      were found bilaterally in the intermediate and ventral gray matter of the caudal
      region of the cervical enlargement. These observations suggest that MIERs may be
      useful to quantitatively assess neurotransmission and functional recovery over
      time after experimental spinal cord injury.

PMID- 16797540
TI  - Trypanosoma cruzi (Kinetoplastida Trypanosomatidae): ecology of the transmission
      cycle in the wild environment of the Andean valley of Cochabamba, Bolivia.
AB  - An active Trypanosoma cruzi transmission cycle maintained by wild rodents in the
      Andean valleys of Cochabamba Bolivia is described. Wild and domestic Triatoma
      infestans with 60% infection with T. cruzi were found and was evidenced in 47.5%
      (rodents) and 26.7% (marsupial) by parasitological and/or serologycal methods.
      Phyllotis ocilae and the marsupial species Thylamys elegans, are the most
      important reservoirs followed by Bolomys lactens and Akodon boliviensis. In spite
      of both genotypes (TCI and TCII) being prevalent in Bolivia, in our study area
      only T. cruzi I is being transmitted. Our data suggest that wild T. infestans and
      wild small mammals play an important role in the maintenance of the transmission
      cycle of T. cruzi. Furthermore, the finding of high prevalence of T. cruzi
      infection in wild T. infestans point to the risk of the dispersion of Chagas'
      disease.

PMID- 16797541
TI  - Proteasomal degradation of the multifunctional regulator YB-1 is mediated by an F
      Box protein induced during programmed cell death.
AB  - F-Box proteins (FBPs) are variable adaptor proteins that earmark protein
      substrates for ubiquination and destruction by the proteasome. Through their N
      terminal F-box motif, they couple specific protein substrates to a catalytic
      machinery known as SCF (Skp-1/Cul1/F-Box) E3-ubiquitin ligase. Typical FBPs bind
      the specific substrates in a phosphorylation dependent manner via their C-termini
      using either leucine rich repeats (LRR) or tryptophan-aspartic acid (WD40)
      domains for substrate recognition. By using a gene trap strategy that selects for
      genes induced during programmed cell death, we have isolated the mouse homolog of
      the hypothetical human F-Box protein 33 (FBX33). Here we identify FBX33 as a
      component of an SCF E3-ubiquitin ligase that targets the multifunctional
      regulator Y-box binding protein 1 (YB-1)/dbpB/p50 for polyubiquitination and
      destruction by the proteasome. By targeting YB-1 for proteasomal degradation,
      FBX33 negatively interferes with YB-1 mediated functions. In contrast to typical
      FBPs, FBX33 has no C-terminal LRR or WD40 domains and associates with YB-1 via
      its N-terminus. The present study confirms the existence of a formerly
      hypothetical F-Box protein in living cells and describes one of its substrates.

PMID- 16797542
TI  - Asp-196-->Ala mutant of Leuconostoc mesenteroides sucrose phosphorylase exhibits
      altered stereochemical course and kinetic mechanism of glucosyl transfer to and
      from phosphate.
AB  - Mutagenesis of Asp-196 into Ala yielded an inactive variant of Leuconostoc
      mesenteroides sucrose phosphorylase (D196A). External azide partly complemented
      the catalytic defect in D196A with a second-order rate constant of 0.031 M-1 s-1
      (pH 5, 30 degrees C) while formate, acetate and halides could not restore
      activity. The mutant utilized azide to convert alpha-D-glucose 1-phosphate into
      beta-D-glucose 1-azide, reflecting a change in stereochemical course of glucosyl
      transfer from alpha-retaining in wild-type to inverting in D196A. Phosphorolysis
      of beta-D-glucose 1-azide by D196A occurred through a ternary complex kinetic
      mechanism, in marked contrast to the wild-type whose reactions feature a common
      glucosyl enzyme intermediate and Ping-Pong kinetics. Therefore, Asp-196 is
      identified unambiguously as the catalytic nucleophile of sucrose phosphorylase,
      and its substitution by Ala forces the reaction to proceed via single
      nucleophilic displacement. D196A is not detectably active as alpha-glucosynthase.

PMID- 16797543
TI  - Isolation and characterisation of conomap-Vt, a D-amino acid containing
      excitatory peptide from the venom of a vermivorous cone snail.
AB  - Cone snail venom is a rich source of bioactives, in particular small disulfide
      rich peptides that disrupt synaptic transmission. Here, we report the discovery
      of conomap-Vt (Conp-Vt), an unusual linear tetradecapeptide isolated from Conus
      vitulinus venom. The sequence displays no homology to known conopeptides, but
      displays significant homology to peptides of the MATP (myoactive
      tetradecapeptide) family, which are important endogenous neuromodulators in
      molluscs, annelids and insects. Conp-Vt showed potent excitatory activity in
      several snail isolated tissue preparations. Similar to ACh, repeated doses of
      Conp-Vt were tachyphylactic. Since nicotinic and muscarinic antagonists failed to
      block its effect and Conp-Vt desensitised tissue remained responsive to ACh, it
      appears that Conp-Vt contractions were non-cholinergic in origin. Finally,
      biochemical studies revealed that Conp-Vt is the first member of the MATP family
      with a d-amino acid. Interestingly, the isomerization of L-Phe to D-Phe enhanced
      biological activity, suggesting that this post-translational modified conopeptide
      may have evolved for prey capture.

PMID- 16797544
TI  - Diffusion NMR studies on fish antifreeze proteins and synthetic analogues.
AB  - Pulsed field gradient spin echo NMR spectroscopy was used to measure diffusion
      coefficients of the alpha-helical type I antifreeze protein from the winter
      flounder, two synthetic derivatives in which the four Thr residues were replaced
      with Val and Ala, respectively, and the low molecular weight fraction antifreeze
      glycoprotein. Under the conditions studied, the natural type I antifreeze protein
      and low molecular weight glycoprotein gave diffusion values that were consistent
      with the presence of monomeric protein in solution. While significant aggregation
      of the Ala analogue was observed (2-10 mM), there was no evidence for aggregation
      in the Val analogue (1-3 mM). These results are compared with previously reported
      solubility and thermal hysteresis data and the implications for the design of
      synthetic antifreeze proteins are discussed.

PMID- 16797545
TI  - The effects of multiple ancestral residues on the Thermus thermophilus 3
      isopropylmalate dehydrogenase.
AB  - Previously, we showed that mutants of Thermus thermophilus 3-isopropylmalate
      dehydrogenase (IPMDH) each containing a residue (ancestral residue) that had been
      predicted to exist in a postulated common ancestor protein often have greater
      thermal stabilities than does the contemporary wild-type enzyme. In this study,
      the combined effects of multiple ancestral residues were analyzed. Two mutants,
      containing multiple mutations, Sup3mut (Val181Thr/Pro324Thr/Ala335Glu) and
      Sup4mut (Leu134Asn/Val181Thr/Pro324Thr/Ala335Glu) were constructed and show
      greater thermal stabilities than the wild-type and single-point mutant IPMDHs do.
      Most of the mutants have similar or improved catalytic efficiencies at 70 degrees
      C when compared with the wild-type IPMDH.

PMID- 16797546
TI  - Branchio-oto-renal syndrome associated mutations in Eyes Absent 1 result in loss
      of phosphatase activity.
AB  - The Eyes Absent (Eya) proteins are tyrosine phosphatases and transcriptional
      activators involved in cell-fate determination and organ development. Mutations
      in the gene encoding Eya homologue 1 have been implicated in the multi-organ
      developmental disorder branchio-oto-renal syndrome (BOR) and in ocular defects.
      Here we report that BOR-associated mutations lead to a loss of phosphatase
      activity in Eya1 proteins, while mutations associated with ocular defects yield
      Eya1 proteins with near normal levels of phosphatase activity. Furthermore we
      demonstrate that the N-terminal domain attenuates the catalytic activity of Eya
      suggesting a mechanism of regulation.

PMID- 16797547
TI  - Dominant negative effects of a Gbeta mutant on G-protein coupled inward rectifier
      K+ channel.
AB  - HEK293 cells were transfected with cDNAs for Gbeta1(W332A) [a mutant Gbeta1],
      Ggamma2, and inward rectifier K+ channels (Kir3.1/Kir3.2). Application of
      Gbeta1gamma2 protein to these cells activated the K+ channels only slightly. When
      mu-opioid receptors and Kir3.1/Kir3.2 were transfected, application of a mu
      opioid agonist induced a Kir3 current. However, co-expression of Gbeta1(W332A)
      suppressed this current. Most likely, Gbeta1(W332A) inhibited the action of the
      endogenous Gbeta. Such a dominant negative effect of Gbeta1(W332A) was also
      observed in neuronal Kir3 channels in locus coeruleus. The mutant, Gbeta1(W332A)
      protein, although inactive, retains its ability to bind Kir3 and prevents the
      wild type Gbeta from activating the channel.

PMID- 16797548
TI  - Accelerated induction of apoptosis in insect cells by baculovirus-expressed SARS
      CoV membrane protein.
AB  - It has been shown that severe acute respiratory syndrome-associated coronavirus
      (SARS-CoV) 3a and 7a proteins, but not membrane (M) protein, induce apoptosis in
      mammalian cells. Upon expression of SARS-CoV M protein using the
      baculovirus/insect cell expression system, however, we found that the expressed M
      protein triggered accelerated apoptosis in insect cells, as characterized by
      rapid cell death, elevated cytotoxicity, cell shrinkage, nuclear condensation and
      DNA fragmentation. Conversely, the M protein expressed in mammalian cells did not
      induce apoptosis. This is the first report describing the induction of apoptosis
      by SARS-CoV M protein in animal cells and possible implications are discussed.

PMID- 16797549
TI  - Targeted disruption of the mouse Asna1 gene results in embryonic lethality.
AB  - The bacterial ArsA ATPase is the catalytic component of an oxyanion pump that is
      responsible for resistance to arsenicals and antimonials. Homologues of the
      bacterial ArsA ATPase are widespread in nature. We had earlier identified the
      mouse homologue (Asna1) that exhibits 27% identity to the bacterial ArsA ATPase.
      To identify the physiological role of the protein, heterozygous Asna1 knockout
      mice (Asna1+/-) were generated by homologous recombination. The Asna1+/- mice
      displayed similar phenotype as the wild-type mice. However, early embryonic
      lethality was observed in homozygous Asna1 knockout embryos, between E3.5
      (E=embryonic day) and E8.5 stage. These findings indicate that Asna1 plays a
      crucial role during early embryonic development.

PMID- 16797551
TI  - Differential status of the renin-angiotensin system of silver sea bream (Sparus
      sarba) in different salinities.
AB  - Silver sea bream (Sparus sarba) is extremely euryhaline and can survive in a wide
      range of salinities (0-70 per thousand). The status of the renin-angiotensin
      system (RAS) in sea bream adapted to different salinities was studied. As
      indicated by plasma Ang II levels, a suppressed status of the RAS was found to
      occur under brackish water conditions; while under hypersaline conditions, an
      activated RAS prevailed, especially in fish adapted to double strength seawater
      (70 per thousand). Captopril successfully blocked the conversion of Ang I to Ang
      II, causing a dramatic drop in plasma Ang II levels, and such decrease was
      accompanied by lowered plasma cortisol levels. The pattern of changes in
      branchial Na-K-ATPase activity in different salinities was similar to those of
      plasma Ang II and cortisol, suggesting a causal regulatory role of Ang II on
      branchial Na-K-ATPase activity. Intraperitoneal injection of Ang II elicited a
      dose-dependent increase in branchial Na-K-ATPase activity in both 33- and 6 per
      thousand-adapted sea bream, but a relatively more intense stimulation of enzyme
      activity occurred in hyposmotic-adapted fish. Abrupt hyposmotic transfer rapidly
      lowered plasma Ang II level but elevated branchial Na-K-ATPase and transiently
      elevated plasma cortisol, indicating that these parameters are not solely
      controlled by Ang II but are also influenced by other hormonal factors that
      change during salinity transfer. Blood volumes of both 33- and 6 per thousand
      adapted sea bream exhibited high stability during short-term salinity transfers
      and after long-term salinity adaptation. Captopril significantly reduced resting
      blood pressure in both 33- and 6 per thousand-adapted sea bream, indicating that
      the RAS was involved in maintenance of resting blood pressure in both
      hyperosmotic and hyposmotic environments. Blood pressure was highly stable during
      abrupt salinity transfer and captopril blockade did not alter such stability. The
      vasopressive effect of angiotensins was more potent in 6 per thousand-adapted sea
      bream. These results showed that the RAS is involved in the maintenance of fluid
      and pressure homeostasis in sea bream and hyposmotic-adapted sea bream has an
      abated RAS status.

PMID- 16797550
TI  - Evidence for a secretory pathway Ca2+-ATPase in sea urchin spermatozoa.
AB  - Plasma membrane, sarco-endoplasmic reticulum and secretory pathway Ca2+-ATPases
      (designated PMCA, SERCA and SPCA) regulate intracellular Ca2+ in animal cells.
      The presence of PMCA, and the absence of SERCA, in sea urchin sperm is known. By
      using inhibitors of Ca2+-ATPases, we now show the presence of SPCA and Ca2+ store
      in sea urchin sperm, which refills by SPCA-type pumps. Immunofluorescence shows
      SPCA localizes to the mitochondrion. Ca2+ measurements reveal that approximately
      75% of Ca2+ extrusion is by Ca2+ ATPases and 25% by Na+ dependent Ca2+
      exchanger/s. Bisphenol, a Ca2+ ATPase inhibitor, completely blocks the acrosome
      reaction, indicating the importance of Ca2+-ATPases in fertilization.

PMID- 16797552
TI  - Activation, silencing and mutually exclusive expression within the var gene
      family of Plasmodium falciparum.
AB  - The var gene family of the human malaria parasite Plasmodium falciparum remains a
      topic of intense research focus due to the key role these antigen-encoding genes
      play in the ability of parasites to cause disease and avoid the human immune
      response. In recent years, as molecular tools for investigating the mechanisms
      that coordinate var gene expression have become more sophisticated, numerous
      insights have been acquired into how parasites manage to regulate transcription
      of this large gene family such that only a single gene is expressed at a time.
      The results of different experimental approaches have implicated mechanisms of
      chromatin modification, subnuclear localisation, promoter/promoter interactions
      and sterile RNAs in the silencing and activation of individual var genes,
      however, the roles that each of these different aspects play remain ill defined.
      In addition, some conflicting data regarding silencing and monoallelic expression
      of recombinant var promoters have recently been published, thus adding to the
      difficulty of understanding this complex phenomenon. In this review, we hope to
      present some of the existing data regarding this controversial topic in a way
      that will be both informative and constructive in our efforts to understand the
      molecular aspects of antigenic variation by malaria parasites.

PMID- 16797554
TI  - Mechanics of bone/PMMA composite structures: an in vitro study of human
      vertebrae.
AB  - The goal of this study was to provide material property data for the cement/bone
      composite resulting from the introduction of PMMA bone cement into human
      vertebral bodies. A series of quasistatic tensile and compressive mechanical
      tests were conducted using cement/bone composite structures machined from cement
      infiltrated vertebral bodies. Experiments were performed both at room temperature
      and at body temperature. We found that the modulus of the composite structures
      was lower than bulk cement (p<0.0001). For compression at 37( composite
      function)C: composite =2.3+/-0.5GPa, cement =3.1+/-0.2GPa; at 23( composite
      function)C: composite =3.0+/-0.3GPa, cement =3.4+/-0.2GPa. Specimens tested at
      room temperature were stiffer than those tested at body temperature (p=0.0004).
      Yield and ultimate strength factors for the composite were all diminished (55
      87%) when compared to cement properties. In general, computational models have
      assumed that cement/bone composite had the same modulus as cement. The results of
      this study suggest that computational models of cement infiltrated vertebrae and
      cemented arthroplasties could be improved by specifying different material
      properties for cement and cement/bone composite.

PMID- 16797553
TI  - Antiplatelet effect of sanguinarine is correlated to calcium mobilization,
      thromboxane and cAMP production.
AB  - Sanguinarine is a plant alkaloid present in the root of Sanguinaria canadensis
      and Poppy fumaria species. Sanguinarine has been used as an antiseptic mouth
      rinse and a toothpaste additive to reduce dental plaque and gingival
      inflammation. In this study, we investigated the antiplatelet effects of
      sanguinarine, aiming to extend its potential pharmacological applications.
      Sanguinarine inhibited platelet aggregation induced by arachidonic acid (AA),
      collagen, U46619 and sub-threshold concentration of thrombin (0.05 U/ml) with
      IC(50) concentrations of 8.3, 7.7, 8.6 and 4.4 microM, respectively. Sanguinarine
      (5-10 microM) inhibited 10-31% of platelet TXB(2) production, but not platelet
      aggregation induced by higher concentration of thrombin (0.1 U/ml). SQ29548, a
      thromboxane receptor antagonist, inhibited the AA-induced platelet aggregation
      but not TXB(2) production. Sanguinarine suppressed cyclooxygenase-1 (COX-1)
      activity (IC(50)=28 microM), whereas its effect on COX-2 activity was minimal.
      Sanguinarine (8, 10 microM) further inhibited the AA-induced Ca(2+) mobilization
      by 27-62%. In addition, SQ22536, an adenylate cyclase inhibitor, attenuated the
      inhibitory effect of sanguinarine toward AA-induced platelet Ca(2+) mobilization
      and aggregation. These results suggest that sanguinarine is a potent antiplatelet
      agent, which activates adenylate cyclase, inhibits platelet Ca(2+) mobilization,
      TXB(2) production as well as suppresses COX-1 enzyme activity. Sanguinarine may
      have therapeutic potential for treatment of cardiovascular diseases related to
      platelet aggregation.

PMID- 16797555
TI  - Ultrasonic model and system for measurement of corneal biomechanical properties
      and validation on phantoms.
AB  - Non-invasive measurement of biomechanical properties of corneas may provide
      important information for ocular disease management and therapeutic procedures.
      An ultrasonic non-destructive evaluation method with a wave propagation model was
      developed to determine corneal biomechanical properties in vivo. In this study,
      we tested the feasibility of the approach in differentiating the mechanical
      properties of soft contact lenses as corneal phantoms. Three material types of
      soft contact lenses (six samples in each group) were measured using a broadband
      ultrasound transducer. The ultrasonic reflections from the contact lenses were
      recorded by a 500MHz/8-bit digitizer, and displayed and processed by a PC. A
      reference signal was recorded to compute the normalized power spectra using Fast
      Fourier Transformation. An inverse algorithm based on least-squares minimization
      was used to reconstruct three parameters of the contact lenses: density,
      thickness, and elastic constants lambda+2micro. The thickness of each sample was
      verified using an electronic thickness gauge, and the averaged density for each
      type of lenses was verified using Archimedes' principle and manufacturer's
      report. Our results demonstrated that the ultrasonic system was able to
      differentiate the elastic properties of the three types of the soft contact
      lenses with statistical significance (P-value<0.001). The reconstructed
      thicknesses and densities agreed well with the independent measurements. Our
      studies on corneal phantoms indicated that the ultrasonic system was sensitive
      and accurate in measuring the material properties of cornea-like structures. It
      is important to optimize the system for in vivo measurements.

PMID- 16797556
TI  - The influence of deceleration forces on ACL strain during single-leg landing: a
      simulation study.
AB  - Anterior cruciate ligament (ACL) injury commonly occurs during single limb
      landing or stopping from a run, yet the conditions that influence ACL strain are
      not well understood. The purpose of this study was to develop, test and apply a
      3D specimen-specific dynamic simulation model of the knee designed to evaluate
      the influence of deceleration forces during running to a stop (single-leg
      landing) on ACL strain. This work tested the conceptual development of the model
      by simulating a physical experiment that provided direct measurements of ACL
      strain during vertical impact loading (peak value 1294N) with the leg near full
      extension. The properties of the soft tissue structures were estimated by
      simulating previous experiments described in the literature. A key element of the
      model was obtaining precise anatomy from segmented MR images of the soft tissue
      structures and articular geometry for the tibiofemoral and patellofemoral joints
      of the knee used in the cadaver experiment. The model predictions were correlated
      (Pearson correlation coefficient 0.889) to the temporal and amplitude
      characteristic of the experimental strains. The simulation model was then used to
      test the balance between ACL strain produced by quadriceps contraction and the
      reductions in ACL strain associated with the posterior braking force. When
      posterior forces that replicated in vivo conditions were applied, the peak ACL
      strain was reduced. These results suggest that the typical deceleration force
      that occurs during running to a single limb landing can substantially reduce the
      strain in the ACL relative to conditions associated with an isolated single limb
      landing from a vertical jump.

PMID- 16797557
TI  - Biomechanical evaluation of fetal calf skull as a model for testing halo-pin
      designs for use in children.
AB  - Rigid immobilization of the cervical spine in children is normally accomplished
      with a halo ring attached to the skull with pins. Concern exists about the risk
      of halo pin complications in small children due to their diminished skull
      thickness. More data are needed on biomechanical properties of the immature skull
      and on safe levels for halo pin penetration forces. The study included halo pin
      penetration tests on 43 skull samples obtained from eight fetal calves, radial
      compression tests of 11 skull samples, and histology. Compressive composite
      elastic modulus (15-139MPa), yield stress (1-5MPa) and composite consolidation
      modulus (188-479MPa) were measured in the skull's radial direction. Pin
      penetration force (F) in Newtons at a pin-penetration depth equal to the original
      skull thickness (T) in mm, was related to T as: F=100+4.3e(T) (R(2)=0.76,
      p<0.0001). However, the 95% confidence limits on individual predictions were
      wide, e.g., 0-475MPa for T=1.5mm and 0-700MPa for T=4mm. These results suggest
      that skull thickness cannot be reliably used to predict halo pin penetration
      loads in a skull with similar structural and mechanical properties to that of the
      fetal calf. Due to the lack of available human data for comparison, the relevance
      of using the fetal calf skull as a model for human infants and young children
      remains inconclusive. Clinical recommendations regarding pediatric halo pin
      penetration loads cannot be made without further study of children's skull
      structure and biomechanical properties.

PMID- 16797558
TI  - Characterization of acrylic resins used for restoration of artworks by pyrolysis
      silylation-gas chromatography/mass spectrometry with hexamethyldisilazane.
AB  - A procedure based on the technique of the pyrolysis-GC/MS has been applied, in
      this work, in order to determine the composition of synthetic acrylic resins
      employed in artworks. The method is based on the on line derivatization of these
      resins using hexamethyldisilazane (HMDS). Results obtained have been compared
      with those others from direct pyrolysis and in situ thermally assisted hydrolysis
      and methylation with tetramethylammonium hydroxide (TMAH). Sensitivity using HMDS
      as derivatising reagent is found similar to that from direct pyrolysis and
      methylation with TMAH. Better resolution of the most representative peaks has
      been also obtained. Additionally, this method reduces the formation of free
      acrylic acid molecules during the pyrolysis process and, in consequence, more
      simplified and well-resolved chromatograms are obtained. Finally, the reported
      procedure has been successfully used for characterizing several acrylic-based
      varnishes and binding media currently used in Fine Arts and real pictorial
      samples from graffiti performed on a Middle Ages bridge.

PMID- 16797559
TI  - Column equilibration effects in gradient elution in reversed-phase liquid
      chromatography.
AB  - The fundamental equations and conditions for linear and stepwise gradient elution
      in reversed-phase liquid chromatography are applied to a mixture of amino acids
      in their underivatized form in aqueous mobile phases modified by 2-propanol,
      acetonitrile or methanol for examining column equilibration effects. It was found
      in all cases systematic deviations between experimental and calculated retention
      times, which are prominent in 2-propanol, reduced in acetonitrile and practically
      negligible in methanol. These deviations appear within a chromatogram just after
      the first change in the composition of the mobile phase reaches the detector and
      last ca. 5 min, where the magnitude of errors reduces exponentially with time.
      Based on these observations we propose a simple way to correct the calculated
      from the gradient elution theory retention times of sample solutes. The origin of
      the discrepancies between theory and experiment as well as their impact on the
      resolution is also discussed.

PMID- 16797560
TI  - Simplified enrichment and identification of environmental peptide toxins using
      antibody-capture surfaces with subsequent mass spectrometry detection.
AB  - The development of a simplified assay for detection of congeners of the
      microcystin (MC) hepatotoxin is described that combines the extreme sensitivity
      of surface-enhanced laser desorption/ionization time-of-flight MS (SELDI TOF-MS)
      with the superior selectivity of immunoaffinity interactions. Using methods
      similar to those of conventional immunoassays, MC standards were captured and
      enriched on immunoreactive ProteinChips coated with an MC-antibody and analyzed
      by TOF-MS. Unlike with conventional immunoassays, individual congeners were
      resolved from mixed pools. Assay conditions were optimized for the quantification
      of MC from untreated raw pond water at concentrations as low as 0.025 microg L(
      1), well below the public health relevant guideline of 1 microg L(-1).

PMID- 16797561
TI  - Affinity partitioning of a Cellulomonas fimi beta-mannanase with a mannan-binding
      module in galactomannan/starch aqueous two-phase system.
AB  - A new approach in affinity separations was studied by partitioning of
      Cellulomonas fimi beta-mannanase (EC 3.2.1.78) containing a mannan-binding module
      in galactomannan/hydroxypropyl starch aqueous two-phase system. Comparison was
      made with a truncated version of C. fimi beta-mannanase which lacked the mannan
      binding module. Results showed that affinity partitioning of the beta-mannanase
      was achieved due to biospecificity of the mannan-binding module towards the top
      phase containing galactomannan. Experiments were conducted at pH 8 to prevent
      enzyme degradation of the phase containing galactomannan. Removal of the top
      phase polymer was accomplished by beta-mannanase degradation allowed by shifting
      to the optimal pH 6. In the combination with the genetic fusion of any given
      protein to the mannan-binding module, the results envision a general procedure
      for primary affinity recovery of such fusion proteins.

PMID- 16797562
TI  - Evaluation of ultra performance liquid chromatography. Part I. Possibilities and
      limitations.
AB  - A practical evaluation of the possibilities and limitations of ultra performance
      liquid chromatography (UPLC) is presented. Acquity BEH columns packed with 1.7
      microm particles are evaluated by means of van Deemter and Knox plots. The
      columns are characterised by high optimal velocities (3.7 mm/s) and low plate
      heights (4.4 microm). Minimum plate heights of 2d(p) were, however, not reached
      and reasons are presented and discussed. Furthermore, the use of 1.7 microm
      particles at 1000 bar is compared, from a theoretical viewpoint, to conventional
      LC (3.5 and 5 microm particles at 400 bar) in terms of analysis speed and
      practical maximum efficiency. Experimental data are used to construct kinetic- or
      "Poppe-plots", which facilitate investigation of the effect of pressure and
      particle size on speed and efficiency. It is found that UPLC conditions hold
      advantages in terms of speed of analysis, for required theoretical plate counts
      up to approximately 80,000.

PMID- 16797563
TI  - On-fibre solid-phase microextraction coupled to conventional liquid
      chromatography versus in-tube solid-phase microextraction coupled to capillary
      liquid chromatography for the screening analysis of triazines in water samples.
AB  - This paper compares the advantages and disadvantages of two different
      configurations for the extraction of triazines from water samples: (1) on-fibre
      solid-phase microextraction (SPME) coupled to conventional liquid chromatography
      (LC); and (2) in-tube SPME coupled to capillary LC. In-tube SPME has been
      effected either with a packed column or with an open capillary column. A critical
      evaluation of the main parameters affecting the performance of each method has
      been carried out in order to select the most suitable approach according to the
      requirements of the analysis. In the on-fibre SPME configuration the fibre
      coating was polydimethylsiloxane (PDMS)-divinylbenzene (DVB). The limits of
      detection (LODs) obtained with this approach under the optimized extraction and
      desorption conditions were between 25 and 125 microg/L. The in-tube SPME approach
      with a C18 packed column (35 mm x 0.5 mm I.D., 5 microm particle size) connected
      to a switching micro-valve provided the best sensitivity; under such
      configuration the LODs were between 0.025 and 0.5 microg/L. The in-tube SPME
      approach with an open capillary column coated with PDMS (30 cm x 0.25 mm I.D.,
      0.25 microm of thickness coating) connected to the injection valve provided LODs
      between 0.1 and 0.5 microg/L. In all configurations UV detection at 230 nm was
      used. Atrazine, simazine, propazine, ametryn, prometryn and terbutryn were
      selected as model compounds.

PMID- 16797564
TI  - Detection enhancement in nano-channels using micro-machined silicon groove.
AB  - The present paper reports on an experimental study of the possibility to use a
      micro-machined detection groove to enhance the detection sensitivity in flat
      rectangular nano-channels for ultra-rapid liquid chromatography separations.
      Transversally running detection grooves with three different axial widths
      (respectively, 2, 4 and 6 microm) and one depth (4.75 microm) were tested in
      glass and silicon channels for the whole range of detectable fluorescein
      isothiocyanate isomer I, FITC, concentrations. The groove with the most square
      like cross-section (i.e., 4 microm wide and 4.75 microm deep) yielded the best
      combination of detection gain and minimal additional band broadening. In a 1cm
      long channel, the effective plate loss caused by the 4 microm wide groove would
      only be of the order of 20%, while the gain in S/N-ratio was of the order of a
      factor of 5. The detection groove concept yields larger gains in silicon channel
      substrates than in glass channel substrates, due to the larger stray light losses
      occurring in the latter.

PMID- 16797565
TI  - Rapid method for the determination of 16 organochlorine pesticides in sesame
      seeds by microwave-assisted extraction and analysis of extracts by gas
      chromatography-mass spectrometry.
AB  - A method for the multiresidue analysis of 16 organochlorine insecticides in
      sesame seeds has been developed. The method is based on the microwave-assisted
      extraction (MAE) of the sesame seeds by the use of a water-acetonitrile mixture
      followed by Florisil clean-up of the extracts and subsequent analysis by gas
      chromatography-mass spectrometry (GC/MS) in the selected ion monitoring (SIM)
      mode. MAE operational parameters (extraction solvent, temperature and time,
      extractant volume) were optimized with respect to extraction efficiency of the
      target compounds from sesame seeds with 46% oil content. Recoveries >80% with
      relative standard deviations (RSD) <12% were obtained for all compounds under the
      selected parameters. The Florisil clean-up step proved sufficient for the removal
      of co-extracted substances so that no adverse effect on the chromatographic
      system was observed. Limit of quantification (LOQ) values were in the range of 5
      10 microg/kg. The proposed method was applied in the analysis of sesame seed
      samples imported to Greece.

PMID- 16797566
TI  - About the C term in the van Deemter's equation of plate height in monoliths.
AB  - Monolithic stationary phases provide high rates of mass transfer at low pressure
      drops and enable much faster separations. Experimental data from published H
      versus u plots obtained with monolithic columns are compiled with an emphasis on
      the mass tranfer (C term of the van Deemter equation). Silica-based monoliths of
      the C18 Chromolith type exhibit a very low C value that does not vary too much
      within a wide range of flow rates. The C term is a function of retention,
      temperature, molecular weight of the solute and mesopore size. Silica-based
      monoliths of capillary format exhibit a slightly higher C value which slightly
      increases with increasing flow rates. The key parameter is the through-pore
      size/skeleton size ratio. Experimental data on polymer-based monoliths retrieved
      from the literature mostly concern acrylate-based material in a capillary format.
      Due to the unique character of every column the scatter of published C values is
      wide. The observed C term are higher than those observed with silica monoliths
      and increase quite linearly with the flow rate. Low-density polymers exhibit
      better performances than high-density polymers. The majority of HETP versus u
      plots are drawn from the peak width at half height. Accurate data should be
      acquired through the second moment of the peak. Some equations for C have been
      derived. An equivalent dispersion particle diameter is a measure of band
      broadening in the mesopores. Mass transfer in silica monoliths is well accounted
      by the theory developed by Guiochon et al.

PMID- 16797567
TI  - Analysis of human hippocampus gangliosides by fully-automated chip-based
      nanoelectrospray tandem mass spectrometry.
AB  - Modern microfluidic devices are currently introduced in electrospray (ESI) mass
      spectrometry (MS), tending to substitute the classical capillary-based ESI
      infusion. Automated systems using the combination of robotized sample handling
      and chip-based ESI are significantly increasing the analysis reproducibility,
      precision, throughput, and efficiency. In the last couple of years our group
      developed the chip-based ESI-MS approach for glycomics in biomedical research and
      applied it for oligosaccharide, glycopeptide and ganglioside investigation. Here
      we report upon the optimization and application of this modern technique for the
      analysis of differential ganglioside expression patterns in human fetal and adult
      hippocampus. By this methodology, ganglioside species exhibiting high degree of
      heterogeneity in the ceramide motifs and biologically-relevant modifications
      could be identified in human hippocampus. The ultra-high reproducibility of the
      experiments uniquely provided by the chip-ESI approach allowed for a reliable MS
      based ganglioside comparative assay. Moreover, the particular feature of chip ESI
      tandem MS to provide structural information at high sensitivity was useful for
      detailed characterization of hippocampus-associated species. The experimental
      data presented in this study indicate the benefits of microfluidic/MS for
      determination of the topospecific brain ganglioside composition and development
      related changes in their expression, which might be of high value in clinical
      investigation and for studies related to ganglioside-based therapy of central
      nervous system diseases.

PMID- 16797568
TI  - Experimental and theoretical studies of sorption kinetics of the anthracycline
      antitumor antibiotic rubomycin on a carboxylic heterogeneous sorbent. Bidisperse
      model of sorption kinetics.
AB  - The present work is devoted to experimental and theoretical studies of the
      sorption kinetics of the anthracycline antitumor antibiotic rubomycin on a
      carboxylic heteroreticular sorbent, BDM-12. The dependence of sorption kinetic
      parameters on the radius of sorbent grains has been experimentally obtained. The
      comparison of experimental data with the predictions of both homogeneous and
      "shell-and-core" models demonstrates the impossibility of using these models for
      adequate description of the rubomycin sorption kinetics on the sorbent, BDM-12.
      We have proposed a theory using the bidisperse model of heterogeneous sorbent
      grain and "linear driving force" approximation. This approximation can be applied
      at 10(-3) < alpha = tauI/tauA < 1, x < 1 and gives the values of the degree of
      process completion with relative errors approximately (alpha x)2. Here tauI and
      tauA are the characteristic times required for diffusion penetration into the
      macro- and microspheres, respectively, x is the ratio of the microsphere and
      macrosphere uptakes at equilibrium. The dependences of two characteristic times
      of the sorption process (for short- and long-time regions) on the radius of a
      sorbent grain have been derived. The predictions of the theory developed here are
      in good agreement with our experimental data and make it possible to calculate
      the kinetic parameters tauI, tauA and x.

PMID- 16797569
TI  - Purification of coenzyme Q10 from fermentation extract: high-speed counter
      current chromatography versus silica gel column chromatography.
AB  - High-speed counter-current chromatography (HSCCC) is applied to the purification
      of coenzyme Q(10) (CoQ(10)) for the first time. CoQ(10) was obtained from a
      fermentation broth extract. A non-aqueous two-phase solvent system composed of
      heptane-acetonitrile-dichloromethane (12:7:3.5, v/v/v) was selected by analytical
      HSCCC and used for purification of CoQ(10) from 500 mg of the crude extract. The
      separation yielded 130 mg of CoQ(10) at an HPLC purity of over 99%. The overall
      results of the present studies show the advantages of HSCCC over an alternative
      of silica gel chromatography followed by recrystallization. These advantages
      extend to higher purity (97.8% versus 93.3%), recovery (88% versus 74.3%) and
      yield (26.4% versus 23.4%). An effort to avoid the toxic, expensive solvent
      CH(2)Cl(2) was unsuccessful, but at least its percentage is low in the solvent
      system.

PMID- 16797570
TI  - Using multi-walled carbon nanotubes as solid phase extraction adsorbents to
      determine dichlorodiphenyltrichloroethane and its metabolites at trace level in
      water samples by high performance liquid chromatography with UV detection.
AB  - Carbon nanotubes (CNTs) are a kind of new carbon-based nano-materials which have
      drawn great attention in many application fields. The potential of multi-walled
      carbon nanotubes (MWNTs) as solid-phase extraction (SPE) adsorbents for the
      preconcentration of environmental pollutants has been investigated in recent
      years. The goal of this work was to investigate the feasibility of MWNTs used as
      SPE adsorbents to enrich dichlorodiphenyltrichloroethane (DDT) and its
      metabolites including 1,1-dichloro-2,2-bis-(4'-chlorophenyl)ethane (DDD) and 1,1
      dichloro-2,2-bis-(4'-chlorophenyl)ethane (DDE) at trace level which are typical
      persistent organic pollutants in environment. Parameters that maybe influence the
      extraction efficiency such as the eluent volume, sample flow rate, sample pH and
      the sample volume were optimized in detail. The experimental results showed the
      excellent linear relationship between peak area and the concentration of DDT and
      its metabolites over the range of 0.2-60 microg L(-1), and the precisions (RSD)
      were 2.3-2.5% under the optimal conditions. The detection limits of proposed
      method could reach 4-13 ng L(-1) based on the ratio of chromatographic signal to
      base line noise (S/N = 3). Satisfied results were achieved when the proposed
      method was applied to determine the four target compounds in realworld water
      samples with spiked recoveries over the range of 89.7-115.5%. All these facts
      indicated that MWCNTs as SPE packing materials coupled to HPLC was an excellent
      alternative for the routine analysis of DDT and its metabolites at trace level in
      environment.

PMID- 16797571
TI  - Bioassay-guided purification and identification of antimicrobial components in
      Chinese green tea extract.
AB  - The Chinese green tea extract was found to strongly inhibit the growth of major
      food-borne pathogens, Escherichia coli O157:H7, Salmonella Typhimurium DT104,
      Listeria monocytogenes, Staphylococcus aureus, and a diarrhoea food-poisoning
      pathogen Bacillus cereus, by 44-100% with the highest activity found against S.
      aureus and lowest against E. coli O157:H7. A bioassay-guided fractionation
      technique was used for identifying the principal active component. A simple and
      efficient reversed-phase high-speed counter-current chromatography (HSCCC) method
      was developed for the separation and purification of four bioactive polyphenol
      compounds, epicatechin gallate (ECG), epigallocatechin gallate (EGCG),
      epicatechin (EC), and caffeine (CN). The structures of these polyphenols were
      confirmed with mass spectrometry. Among the four compounds, ECG and EGCG were the
      most active, particularly EGCG against S. aureus. EGCG had the lowest MIC90
      values against S. aureus (MSSA) (58 mg/L) and its methicilin-resistant S. aureus
      (MRSA) (37 mg/L). Scanning electron microscopy (SEM) studies showed that these
      two compounds altered bacterial cell morphology, which might have resulted from
      disturbed cell division. This study demonstrated a direct link between the
      antimicrobial activity of tea and its specific polyphenolic compositions. The
      activity of tea polyphenols, particularly EGCG on antibiotics-resistant strains
      of S. aureus, suggests that these compounds are potential natural alternatives
      for the control of bovine mastitis and food poisoning caused by S. aureus.

PMID- 16797573
TI  - Destructive aggregation: aggregation with collision-induced breakage.
AB  - Mean-field population balance equations are used to describe the evolution of
      particle size distributions in a wide variety of systems undergoing simultaneous
      aggregation and breakage. In this paper we develop a population balance that
      includes aggregation combined with collision-induced particle breakage for
      arbitrary fragment distribution functions, provided that this distribution
      function depends only on the total mass of the particles undergoing a collision.
      We then develop a specific distribution function for arbitrary two-body
      collisions by postulating that each collision produces a transition-state
      aggregate having the morphology of a linear polymer. The behavior of the
      resulting equation is then analyzed for the case in which the collision kernel is
      a constant, and partial analytical solutions are derived and compared to
      corresponding Monte-Carlo simulation results. The computer simulations are then
      used to validate a proposed scaling law for the steady-state particle size
      distribution. Lastly, the behavior of the aggregation with collision-induced
      breakage population balance equation is compared and contrasted with the behavior
      of an analogous aggregation with linear-breakage population balance equation.

PMID- 16797572
TI  - Analysis of ethambutol and methoxyphenamine by capillary electrophoresis with
      electrochemiluminescence detection.
AB  - A capillary electrophoresis (CE) coupled with electrochemiluminescence (ECL)
      detection method for the analysis of ethambutol (EB) and methoxyphenamine (MP)
      has been investigated. Complete separation of EB and MP was achieved in 8 min
      using a background electrolyte of 20 mM sodium phosphate at pH 10.0 and a
      separation voltage of 9 kV. ECL detection was performed with an indium/tin oxide
      (ITO) working electrode biased at 1.4 V (versus a Pt wire reference) in a 200 mM
      sodium phosphate buffer (pH 8.0) containing 3.5 mM Ru(bpy)3(2+) (where bpy = 2,2'
      bipyridyl). Linear correlation (r > or = 0.993) between ECL intensity and drug
      concentration was obtained in the range 2-50 ng/ml. The limits of detection
      (LODs) for EB and MP in water were 1.0 and 0.9 ng/ml, respectively. The relative
      standard deviation values on peak size (10 ng/ml level) and migration time for
      the two drugs were in the ranges 5-8 and 0.2-0.7% (n = 7), respectively.
      Applicability of the CE-ECL method to the analysis of human plasma spiked with EB
      and MP was examined. The LODs for EB and MP in plasma were 0.4 and 0.3 microg/ml,
      respectively.

PMID- 16797574
TI  - Micrometer-sized rodlike structure formed by the secondary assembly of
      cyclodextrin nanotube.
AB  - In this work, we report the observation on the self-assembly of beta-CD nanotube
      induced by 2-phenyl-5-(4-diphenylyl)1,3,4-oxadiazole (PBD) molecule with
      fluorescence microscopy and transmission electron microscopy (TEM). Micrometer
      sized rodlike structure is formed by the secondary assembly of cyclodextrin
      nanotube driven by the inter-nanotubular hydrogen bonding. The effects of pH
      value, urea, DMF and NaCl on the formation of the rodlike structure are
      investigated. Dynamic light scattering (DLS) is applied to further characterize
      the formation of the PBD-beta-CD nanotube. The effect of light scattering on the
      measurement of fluorescence anisotropy of PBD in the aqueous solutions of beta-CD
      is corrected. A new mechanism of cyclodextrin aggregation is proposed for this
      system.

PMID- 16797575
TI  - High ionic strength electrokinetics of melamine-formaldehyde latex.
AB  - The electrokinetic potential of melamine-formaldehyde latex at high ionic
      strengths was measured by means of two different instruments. The present study
      confirms that the zeta potentials in 1 M 1-1 electrolyte solutions can be as high
      as +/-20 mV. The IEP of latex at low ionic strengths was at pH 11. The increase
      in the electrolyte concentration induced a shift in the IEP to low pH for all
      studied salts, and this indicates specific adsorption of the anions. The
      magnitude of the shift depends chiefly on the nature of the anion and increases
      in the series Cl < NO(3) = Br < I, and the nature of the cation (Li, Na, K, Cs)
      plays a rather insignificant role.

PMID- 16797576
TI  - Drop formation via breakup of a liquid bridge in an AC electric field.
AB  - Experimental results are presented for the study of drop formation mechanism in a
      newly proposed electrohydrodynamic (EHD) method of drop generation in an AC
      electric field. In the method, a small drop is generated in two stages. A pendant
      drop is elongated with large oscillation by an electric force in the first stage.
      Then, it undergoes formation and breakup of a liquid bridge between the upper
      nozzle and the insulator-coated lower flat plate in the second stage. It is found
      that there exists a resonant frequency for maximum oscillation, which leads to an
      efficient drop formation in the latter stage. It is also found that breakup of
      liquid bridge is accelerated by the electrowetting tension acting on the drop
      perimeter contacting the insulator-coated flat plate. Thus the whole procedure of
      drop formation depends heavily on the frequency of AC field and the properties of
      the insulator such as hydrophilicity, thickness, and the dielectric constant. It
      is demonstrated that a wide range of drop size, from picoliter to nanoliter, can
      be obtained by controlling such key parameters without changing the nozzle
      diameter.

PMID- 16797578
TI  - Probing particle size distributions in natural surface waters from 15 nm to 2
      microm by a combination of LIBD and single-particle counting.
AB  - We present a technique for measuring colloid size distributions between 15 nm and
      2 microm at concentrations relevant to natural surface waters. Two particle
      measuring methods are combined: laser-induced breakdown detection (LIBD), which
      allows the quantification of colloid size distributions below 400 nm, and a
      commercial single-particle counter that extends the accessible size range up to
      two mum. Centrifugation was used in order to separate micrometer sized particles
      for the LIBD measurement. The feasibility is demonstrated on water of Lake Brienz
      (Switzerland) and the River Pfinz (Germany) and the particle size distributions
      follow Pareto's law even down to 15 nm in both cases.

PMID- 16797577
TI  - The influence of subphase temperature on miltefosine-cholesterol mixed
      monolayers.
AB  - Effects of the subphase temperature on the surface pressure (pi)-area (A)
      isotherms of mixed monolayers of miltefosine (hexadecylphosphocholine), a
      potential anticancer drug, and cholesterol were investigated at the air/water
      interface, which were supplemented with Brewster angle microscopy (BAM)
      observations. Comparison of the collapse pressure values, mean molecular areas,
      excess areas and excess free energy of mixing between the mixed monolayer at
      various molar ratios and the pure component monolayers showed that, regardless of
      the subphase temperature, the investigated miltefosine-cholesterol system is much
      more stable than that the pure component monolayers, suggesting strong attractive
      interactions between miltefosine and cholesterol in mixed monolayers. As a
      consequence, it was postulated that stable "complexes" of the two components
      could form at the interface, for which stoichiometry may vary with the subphase
      temperature. Such "surface complexes" should be responsible for the contraction
      of the mean molecular area and thus the high stability of the mixed monolayer.

PMID- 16797579
TI  - Pore surface fractal analysis of palladium-alumina ceramic membrane using Frenkel
      Halsey-Hill (FHH) model.
AB  - The alumina ceramic membrane has been modified by the addition of palladium in
      order to improve the H(2) permeability and selectivity. Palladium-alumina ceramic
      membrane was prepared via a sol-gel method and subjected to thermal treatment in
      the temperature range 500-1100 degrees C. Fractal analysis from nitrogen
      adsorption isotherm is used to study the pore surface roughness of palladium
      alumina ceramic membrane with different chemical composition (nitric acid, PVA
      and palladium) and calcinations process in terms of surface fractal dimension, D.
      Frenkel-Halsey-Hill (FHH) model was used to determine the D value of palladium
      alumina membrane. Following FHH model, the D value of palladium-alumina membrane
      increased as the calcinations temperature increased from 500 to 700 degrees C but
      decreased after calcined at 900 and 1100 degrees C. With increasing palladium
      concentration from 0.5 g Pd/100 ml H(2)O to 2 g Pd/100 ml H(2)O, D value of
      membrane decreased, indicating to the smoother surface. Addition of higher amount
      of PVA and palladium reduced the surface fractal of the membrane due to the
      heterogeneous distribution of pores. However, the D value increased when nitric
      acid concentration was increased from 1 to 15 M. The effect of calcinations
      temperature, PVA ratio, palladium and acid concentration on membrane surface
      area, pore size and pore distribution also studied.

PMID- 16797580
TI  - Enhanced nucleophilic reactivity of hydroxamate ions in some novel micellar
      systems for the cleavage of parathion.
AB  - The reactivity of three alpha-nucleophiles, i.e. N-phenylbenzohydroxamate,
      benzohydroxamate and salicylhydroxamate ions towards cleavage of p
      nitrophenyldiethyl phosphorothioate (Parathion) is considerably enhanced in the
      presence of cationic surfactant, i.e. cetyltrimethylammonium bromide. The
      esterolytic properties of N-phenylbenzohydroxamate ion for parathion have also
      been examined in two novel surfactants, viz. cetyltriphenylphosphonium bromide
      and cetyldimethyl ethanol ammonium bromide. The cetyldimethyl ethanol ammonium
      bromide is more reactive. The rate-surfactant profiles have been fitted with
      pseudophase model.

PMID- 16797581
TI  - Uric acid recycling in the shield bug, Parastrachia japonensis (Hemiptera:
      Parastrachiidae), during diapause.
AB  - Nymphs of the univoltine shield bug, Parastrachia japonensis grow by feeding on
      the drupes of their sole food plant, which are available for only 2 weeks a year.
      The new adults soon enter a reproductive diapause and survive without feeding for
      at least 10 months up to 2 years. Uric acid was found to be the predominant
      component among four waste nitrogenous compounds, i.e., uric acid, allantoin,
      allantoic acid and urea in the body of both nymphs and adults in all stages, and
      to be predominantly excreted by the nymphs and reproductive adults. However,
      adults in diapause excreted negligible amounts of these compounds. Erwinia-like
      bacteria were found exclusively in the cecum of midgut, in which three uricolytic
      enzymes, i.e., uricase, allantoinase and allantoicase were detected. Ninety % of
      adults in diapause could survive on water for 9 months, but those given 0.02%
      rifampicin aqueous solution all died within this period, with significant
      reduction of the bacteria and uricase activity in the cecum. Rifampicin treatment
      resulted in a considerable reduction of free amino acids, especially proline in
      the hemolymph. These results suggest that uric acid is recycled as an amino acid
      source with the aid of Erwinia-like bacteria, and uricase functions as a key
      enzyme for this process.

PMID- 16797582
TI  - Expression of Cry1Ac cadherin receptors in insect midgut and cell lines.
AB  - Cadherin-like proteins have been identified as putative receptors for the
      Bacillus thuringiensis Cry1A proteins in Heliothis virescens and Manduca sexta.
      Immunohistochemistry showed the cadherin-like proteins are present in the insect
      midgut apical membrane, which is the target site of Cry toxins. This subcellular
      localization is distinct from that of classical cadherins, which are usually
      present in cell-cell junctions. Immunoreactivity of the cadherin-like protein in
      the insect midgut was enhanced by Cry1Ac ingestion. We also generated a stable
      cell line Flp-InT-REX-293/Full-CAD (CAD/293) that expressed the H. virescens
      cadherin. As expected, the cadherin-like protein was mainly localized in the cell
      membrane. Interestingly, toxin treatment of CAD/293 cells caused this protein to
      relocalize to cell membrane subdomains. In addition, expression of H. virescens
      cadherin-like protein affects cell-cell contact and cell membrane integrity when
      the cells are exposed to activated Cry1Ab/Cry1Ac.

PMID- 16797583
TI  - Cry toxin mode of action in susceptible and resistant Heliothis virescens larvae.
AB  - Many pest insect species are effectively controlled by Bacillus thuringiensis
      (Bt) Cry toxins delivered in plants and biopesticides. Since the insect midgut
      epithelium contains receptors and other molecules that determine Bt toxicity,
      characterization of these molecules is necessary for sustained usage of Bt
      toxins. Studies of Bt susceptible and resistant strains of Heliothis virescens
      have provided insights into resistance mechanisms and toxin receptors. For
      example, the first gene identified as involved in high levels of Cry1Ac
      resistance in H. virescens encodes a cadherin-like protein, a functional Cry1A
      receptor in Lepidoptera. This manuscript discusses the most updated information
      on the mode of action of Cry1A toxins obtained from the characterization of
      resistant mechanisms in H. virescens strains. Our studies are focused on
      biochemical and molecular comparison of a susceptible and three resistant H.
      virescens strains to identify alterations that correlate with toxin resistance.
      Following this approach we have been able to identify an alkaline phosphatase
      (HvALP) as a potential receptor and tested the utility of this protein as a
      marker for resistance to Cry1Ac. Comparison of brush border proteomes from
      susceptible and resistant larvae has allowed us to identify additional molecules
      directly involved in the toxicity process.

PMID- 16797584
TI  - Urotensin-II blockade with SB-611812 attenuates cardiac dysfunction in a rat
      model of coronary artery ligation.
AB  - Expression of urotensin II (UII) is significantly elevated in the hearts of
      patients with congestive heart failure (CHF). Recent reports have also shown
      increased plasma levels of UII in patients with CHF, and these levels correlated
      with the severity of disease. We therefore hypothesized that blockade of UII
      signaling would improve cardiac function in a rat model of CHF. CHF was induced
      in rats by ligating the left coronary artery. Animals were randomized to either
      treatment with a specific UT receptor antagonist, SB-611812 (30 mg/kg/day, UID by
      gavage), or vehicle, starting either 30 min prior to coronary ligation (early
      treatment) or 10 days after ligation (delayed treatment). Treatment drug or
      vehicle was administered daily thereafter for 8 weeks. We measured cardiac
      function and evaluated the levels of mRNA expression for mediators of CHF. In
      addition, we evaluated UII and UT protein levels using immunohistochemistry and
      Western blotting. Cardiomyocyte hypertrophy was evaluated by measuring
      cardiomyocyte cross-sectional area. Animals with CHF showed increased UII and UT
      expression as evidenced by immunohistochemistry and Western blotting. Treatment
      with the SB-611812 significantly reduced overall mortality, left ventricular end
      diastolic pressure by 72%, lung edema by 71%, right ventricular systolic pressure
      by 92%, central venous pressure by 59%, cardiomyocyte hypertrophy by 54%, and
      ventricular dilatation by 79% (P < 0.05). Therefore, blockade of the UT receptor
      reduced mortality and improved cardiac function in this model of myocardial
      infarction and CHF, suggesting an important role for UII in the pathogenesis of
      this condition.

PMID- 16797585
TI  - The unfolded state of the villin headpiece helical subdomain: computational
      studies of the role of locally stabilized structure.
AB  - The 36 residue villin headpiece helical subdomain (HP36) is one of the fastest
      cooperatively folding proteins, folding on the microsecond timescale. HP36's
      simple three helix topology, fast folding and small size have made it an
      attractive model system for computational and experimental studies of protein
      folding. Recent experimental studies have explored the denatured state of HP36
      using fragment analysis coupled with relatively low-resolution spectroscopic
      techniques. These studies have shown that there is apparently only a small
      tendency to form locally stabilized secondary structure. Here, we complement the
      experimental studies by using replica exchange molecular dynamics with explicit
      solvent to investigate the structural features of these peptide models of
      unfolded HP36. To ensure convergence, two sets of simulations for each fragment
      were performed with different initial structures, and simulations were continued
      until these generated very similar final ensembles. These simulations reveal low
      populations of native-like structure and early folding events that cannot be
      resolved by experiment. For each fragment, calculated J-coupling constants and
      helical propensities are in good agreement with experimental trends. HP-1,
      corresponding to residues 41 to 53 and including the first alpha-helix, contains
      the highest helical population. HP-3, corresponding to residues 62 through 75 and
      including the third alpha-helix, contains a small population of helical turn
      residing at the N terminus while HP-2, corresponding to residues 52 through 61
      and including the second alpha-helix, formed little to no structure in isolation.
      Overall, HP-1 was the only fragment to adopt a native-like conformation, but the
      low population suggests that formation of significant structure only occurs after
      formation of specific tertiary interactions.

PMID- 16797586
TI  - Dynamics of mutation and recombination in a replicating population of
      complementing, defective viral genomes.
AB  - In a previous study, we documented that serial passage of a biological clone of
      foot-and-mouth disease virus (FMDV) at high multiplicity of infection (moi) in
      cell culture resulted in viral populations dominated by defective genomes that
      included internal in-frame deletions, affecting the L and capsid-coding regions,
      and were infectious by complementation. In the present study, analyses of the
      defective genomes present in individual viral plaques, and of consensus
      nucleotide sequences determined for the entire genomes of sequential samples,
      have revealed a continuous dynamics of mutation and recombination. At some points
      of high genetic instability, multiple minority genomes with different internal
      deletions co-existed in the population. At later passages, a new defective RNA
      arose and displaced a related, previously dominant RNA. Nucleotide sequences of
      the different genomic forms found in sequential isolates have revealed an
      accumulation of mutations at an average rate of 0.12 substitutions per genome per
      passage. At the regions around the deletion sites, substantial, minor or no
      nucleotide sequence identity is found, suggesting relaxed sequence requirements
      for the occurrence of internal deletions. Competition experiments indicate a
      selective advantage of late phase defective genomes over their precursor forms.
      The defective genome-based FMDV retained an expansion of host cell tropism,
      undergone by the standard virus at a previous stage of the same evolutionary
      lineage. Thus, despite a complex dynamics of mutation and recombination, and
      phases of high genetic instability, a biologically relevant phenotypic trait was
      stably maintained after the evolutionary transition towards a primitive genome
      segmentation. The results extend the concept of a complex spectrum of mutant
      genomes to a complex spectrum of defective genomes in some evolutionary
      transitions of RNA viruses.

PMID- 16797587
TI  - Interpreting the aggregation kinetics of amyloid peptides.
AB  - Amyloid fibrils are insoluble mainly beta-sheet aggregates of proteins or
      peptides. The multi-step process of amyloid aggregation is one of the major
      research topics in structural biology and biophysics because of its relevance in
      protein misfolding diseases like Alzheimer's, Parkinson's, Creutzfeld-Jacob's,
      and type II diabetes. Yet, the detailed mechanism of oligomer formation and the
      influence of protein stability on the aggregation kinetics are still matters of
      debate. Here a coarse-grained model of an amphipathic polypeptide, characterized
      by a free energy profile with distinct amyloid-competent (i.e. beta-prone) and
      amyloid-protected states, is used to investigate the kinetics of aggregation and
      the pathways of fibril formation. The simulation results suggest that by simply
      increasing the relative stability of the beta-prone state of the polypeptide,
      disordered aggregation changes into fibrillogenesis with the presence of
      oligomeric on-pathway intermediates, and finally without intermediates in the
      case of a very stable beta-prone state. The minimal-size aggregate able to form a
      fibril is generated by collisions of oligomers or monomers for polypeptides with
      unstable or stable beta-prone state, respectively. The simulation results provide
      a basis for understanding the wide range of amyloid-aggregation mechanisms
      observed in peptides and proteins. Moreover, they allow us to interpret at a
      molecular level the much faster kinetics of assembly of a recently discovered
      functional amyloid with respect to the very slow pathological aggregation.

PMID- 16797588
TI  - Crystal structure of the monomeric porin OmpG.
AB  - The outer membrane (OM) of Gram-negative bacteria contains a large number of
      channel proteins that mediate the uptake of ions and nutrients necessary for
      growth and functioning of the cell. An important group of OM channel proteins are
      the porins, which mediate the non-specific, diffusion-based passage of small
      (<600 Da) polar molecules. All porins of Gram-negative bacteria that have been
      crystallized to date form stable trimers, with each monomer composed of a 16
      stranded beta-barrel with a relatively narrow central pore. In contrast, the OmpG
      porin is unique, as it appears to function as a monomer. We have determined the X
      ray crystal structure of OmpG from Escherichia coli to a resolution of 2.3 A. The
      structure shows a 14-stranded beta-barrel with a relatively simple architecture.
      Due to the absence of loops that fold back into the channel, OmpG has a large (
      approximately 13 A) central pore that is considerably wider than those of other
      E. coli porins, and very similar in size to that of the toxin alpha-hemolysin.
      The architecture of the channel, together with previous biochemical and other
      data, suggests that OmpG may form a non-specific channel for the transport of
      larger oligosaccharides. The structure of OmpG provides the starting point for
      engineering studies aiming to generate selective channels and for the development
      of biosensors.

PMID- 16797589
TI  - Crystal structures of BchU, a methyltransferase involved in bacteriochlorophyll c
      biosynthesis, and its complex with S-adenosylhomocysteine: implications for
      reaction mechanism.
AB  - BchU plays a role in bacteriochlorophyll c biosynthesis by catalyzing methylation
      at the C-20 position of cyclic tetrapyrrole chlorin using S-adenosylmethionine
      (SAM) as a methyl source. This methylation causes red-shifts of the electronic
      absorption spectrum of the light-harvesting pigment, allowing green
      photosynthetic bacteria to adapt to low-light environments. We have determined
      the crystal structures of BchU and its complex with S-adenosylhomocysteine (SAH).
      BchU forms a dimer and each subunit consists of two domains, an N-terminal domain
      and a C-terminal domain. Dimerization occurs through interactions between the N
      terminal domains and the residues responsible for the catalytic reaction are in
      the C-terminal domain. The binding site of SAH is located in a large cavity
      between the two domains, where SAH is specifically recognized by many hydrogen
      bonds and a salt-bridge. The electron density map of BchU in complex with an
      analog of bacteriochlorophyll c located its central metal near the SAH-binding
      site, but the tetrapyrrole ring was invisible, suggesting that binding of the
      ring to BchU is loose and/or occupancy of the ring is low. It is likely that
      His290 acts as a ligand for the central metal of the substrate. The orientation
      of the substrate was predicted by simulation, and allows us to propose a
      mechanism for the BchU directed methylation: the strictly conserved Tyr246
      residue acts catalytically in the direct transfer of the methyl group from SAM to
      the substrate through an S(N)2-like mechanism.

PMID- 16797590
TI  - The three-dimensional arcitecture of the EJC core.
AB  - The exon junction complex (EJC) is a macromolecular complex deposited at splice
      junctions on mRNAs as a consequence of splicing. At the core of the EJC are four
      proteins: eIF4AIII, a member of the DExH/D-box family of NTP-dependent RNA
      binding proteins, Y14, Magoh, and MLN51. These proteins form a stable
      heterotetramer that remains bound to the mRNA throughout many different cellular
      environments. We have determined the three-dimensional (3D) structure of this EJC
      core using negative-stain random-conical tilt electron microscopy. This structure
      represents the first structure of a DExH/D-box protein in complex with its
      binding partners. The EJC core is a four-lobed complex with a central channel and
      dimensions consistent with its known RNA footprint of about ten nucleotides.
      Using known X-ray crystallographic structures and a model of three of the four
      components, we propose a model for complex assembly on RNA and explain how
      Y14:Magoh may influence eIF4AIII's RNA binding.

PMID- 16797591
TI  - Predictors of acute treatment response in patients with a first episode of non
      affective psychosis: sociodemographics, premorbid and clinical variables.
AB  - Approximately 60% of patients with a first episode of psychosis will
      significantly reduce the severity of their positive symptomatology with
      antipsychotic drugs. The aim of this study was to investigate predictors of
      response to antipsychotic treatment during the first episode of non-affective
      psychosis. 172 patients (107 male) with a diagnosis of schizophreniform,
      schizophrenia, schizoaffective, brief reactive psychosis, schizotypal personality
      disorder or psychosis non-otherwise specified entered the study.
      Sociodemographic, premorbid and clinical data at baseline were evaluated.
      Unpaired t-test for continuous and chi2 for categorical data, respectively, were
      used to compare responders and non-responders selected variables. Multivariate
      logistic regression was used to establish a prediction model. 57.6% of study
      subjects (99 of 172) responded to antipsychotic treatment. The following
      variables were significantly associated with less likelihood of response: 1.-
      lower severity of general psychopathology, positive symptoms and disorganized
      symptoms at baseline; 2.--earlier age of onset; 3.--diagnosis of schizophrenia;
      4.--longer DUP; 5.--poorer premorbid adjustment during adolescence, and 6.-
      hospitalization. Multivariate logistic regression demonstrated that differences
      between responders and non-responders were largely accounted for by BPRS total
      score, age of onset, premorbid adjustment at early adolescence, and diagnosis.
      Patients with an early age of onset of schizophrenia, a poor premorbid adolescent
      functioning, and with a lower severity of psychopathology at intake seem to have
      a decrease likelihood of responding to antipsychotic treatment. Helping
      clinicians to identify non-responders is meant as a first step to optimise
      therapeutic effort to benefit individuals in this vulnerable group.

PMID- 16797593
TI  - A dopamine agonist, pramipexole, and cognitive functions in Parkinson's disease.
AB  - The cognitive performance of 55 non-demented idiopathic Parkinson's disease (PD)
      patients treated with levodopa alone or receiving dopamine agonist pramipexole as
      add-on therapy to levodopa was evaluated in the present study during 6 months of
      treatment. Neuropsychological tests were administered two times. In the first
      assessment to differentiate test sensitive to cognitive changes typical for PD
      control group was also assessed. After 6 months of treatment PD patients were
      retested only with tests that differentiate them from control group. Compared to
      controls PD patients showed inferior performance on Stroop Interference test,
      Trail Making test, letter fluency and Hooper Visual Organization Test. No
      statistically significant differences between two groups and first and second
      neuropsychological assessment were found. Present findings indicate that
      pramipexole as add-on therapy to levodopa is safe in non-demented PD patients in
      terms of the effect on cognitive performance.

PMID- 16797594
TI  - The morphological basis of mental dysfunction in Parkinson's disease.
AB  - Mental dysfunction including dementia in Parkinson's disease (PD), the incidence
      of which averages 20-40%, is suggested to have six-fold lifetime risk compared to
      age-matched controls. It is caused by a variety of functional and pathological
      lesions ranging from damage to subcortical-cortical networks to cortical and
      limbic Lewy body and neuritic Alzheimer pathologies, the relationship and impact
      of which are still under discussion. Based on two consecutive autopsy series of
      PD, with prevalence of cognitive impairment of 33% to 35.7%, its essential
      morphological changes and their impact on the natural history (survival) are
      discussed. Whereas cortical Lewy body stages 5 and 6 without additional
      pathologies only rarely were associated with dementia, around 20% of demented PD
      cases were classified as dementia with Lewy bodies (DLB) with variable degrees of
      Alzheimer (AD) pathology, and around one third showed severe neuritic AD lesions
      which occurred in PD patients with later disease onset and significantly shorter
      survival. Frequent close relations in the severity between alpha-synuclein and
      tau-pathologies suggest synergistic reaction and common underlying pathogenesis
      of both lesions. Clinico-pathological studies in PD showed a significantly
      negative relation between cognitive impairment and neuritic AD lesions somewhat
      different from that in AD, suggesting that neuritic AD pathology, either alone or
      in combination with cortical and limbic Lewy bodies, are major causes of mental
      and cognitive dysfunction in PD.

PMID- 16797595
TI  - Effect of combined therapy with thrombolysis and citicoline in a rat model of
      embolic stroke.
AB  - An approach combining reperfusion mediated by thrombolytics with pharmacological
      neuroprotection aimed at inhibiting the physiopathological disorders responsible
      for ischemia-reperfusion damage, could provide an optimal treatment of ischemic
      stroke. We investigate, in a rat embolic stroke model, the combination of rtPA
      with citicoline as compared to either alone as monotherapy, and whether the
      neuroprotector should be provided before or after thrombolysis to achieve a
      greater reduction of ischemic brain damage. One hundred and nine rats have been
      studied: four were sham-operated and the rest embolized in the right internal
      carotid artery with an autologous clot and divided among 5 groups: 1) control; 2)
      iv rtPA 5 mg/kg 30 min post-embolization 3) citicoline 250 mg/kg ip x3 doses, 10
      min, 24 h and 48 h post-embolization; 4) citicoline combined with rtPA following
      the same pattern; 5) rtPA combined with citicoline, with a first dose 10 min
      after thrombolysis. Mortality, neurological score, volume of ischemic lesion and
      neuronal death (TUNEL) after 72 h and plasma levels of IL-6 and TNF-alpha, were
      considered to assess ischemic brain damage. Compared with controls, the use of
      citicoline after thrombolysis produced the greatest reduction of mortality caused
      by the ischemic lesion (p<0.01), infarct volume (p=0.027), number of TUNEL
      positive cells in striatum (p=0.014) and plasma levels of TNF-alpha at 3 h
      (p=0.027) and 72 h (p=0.011). rtPA induced reperfusion provided a slight non
      significant reduction of infarct volume and neuronal death, but it reduced
      mortality due to brain damage (p<0.01) although an increase in the risk of fatal
      bleeding was noted. CiT as monotherapy only produced a significant reduction of
      neuronal death in striatum (p=0.014). The combination of CiT before rtPA did not
      add any benefit to rtPA alone. The superiority of the combined treatment with
      rtPA followed by citicoline suggests that early reperfusion should be followed by
      effective neuroprotection to inhibit ischemia-reperfusion injury and better
      protect the tissue at risk.

PMID- 16797596
TI  - Are freezing of gait (FOG) and panic related?
AB  - We studied 109 consecutive patients who were unselected for freezing of gait
      (FOG), anxiety, depression, or panic attacks. All patients completed a panic
      assessment, the Hamilton Anxiety Scale and the Hamilton Depression Scale.
      Patients were divided into those with FOG or no FOG based on their answer to the
      FOG question on the Activities of Daily Living part of the UPDRS. Patients with
      FOG were more disabled, had more "wearing off", dyskinesia, leg dystonia, and
      postural instability. They were also more anxious and more likely to panic. FOG,
      in many patients, is increased by anxiety and panic.

PMID- 16797597
TI  - Fluctuation in the physical environment as a mechanism for reinforcing
      evolutionary transitions.
AB  - We hypothesize a mechanism for reinforcing transitions between levels of
      selection, involving physiological homeostasis and amplification of variation in
      the physical environment. Groups experience a stronger selection pressure than
      individuals for homeostasis with respect to reproductively limiting variables,
      because their greater longevity exposes them more often to suboptimal physical
      conditions, and greater physical size means they encompass a larger fraction of
      any resource/nutrient gradient. Groups achieve homeostasis by differentiation
      into microcosms with specialist functions, e.g. cell types. Such differentiation
      is more limited in individuals due to their smaller size and shorter lifespan.
      Hence tolerance of fluctuation in certain physical variables is proposed to be
      weaker in individuals than in groups. We show that a trait providing increased
      tolerance (alpha) to fluctuation (V-V(opt)) in a limiting abiotic variable (V),
      at relative fitness cost (C), can increase from rarity if the condition alpha.mid
      R:V-V(opt)|>C is met. Groups also sequester larger absolute quantities of
      resource than individuals, and group death is less frequent, hence the population
      dynamics of groups cause resource/nutrient availability to fluctuate with greater
      amplitude than that of individuals. Increasing the amplitude of fluctuation in a
      reproductively limiting environmental variable is proposed as a mechanism by
      which a group can limit reproduction of parasitic "cheat" individuals. Enhancing
      physical fluctuation is frequency dependent, hence only an increase in tolerance
      to fluctuation can explain the group's increase from rarity. However, once groups
      reach intermediate frequencies, a positive feedback process can be initiated in
      which a differentiated group enhances physical fluctuation beyond the tolerance
      of any "cheat", and in so doing enhances the selection pressure it experiences
      for homeostasis. This may help explain the persistence of transitions in
      individuality, and the coincidence of some such transitions with periods of
      change and oscillation in global scale environmental variables.

PMID- 16797598
TI  - Sodium as the major mediator of NO-induced cell death in cultured hepatocytes.
AB  - NO has been shown to induce cellular injury via inhibition of the mitochondrial
      respiratory chain and/or oxidative/nitrosative stress. Here, we studied which
      mechanism and downstream mediator is responsible for NO toxicity to hepatocytes.
      When cultured rat hepatocytes were incubated with spermineNONOate (0.01-2 mM) at
      2, 5, 21 and 95% O(2) in Krebs-Henseleit buffer (37 degrees C), spermineNONOate
      caused concentration-dependent hepatocyte death (lactate dehydrogenase release,
      propidium iodide uptake) with morphological features of both apoptosis and
      necrosis. Increasing O(2) concentrations protected hepatocytes from NO-induced
      injury. Steady-state NO concentrations were lower at higher O(2) concentrations,
      suggesting formation of reactive nitrogen oxide species. Despite this, the
      scavenger ascorbic acid was hardly protective. In contrast, at equal NO
      concentrations loss of viability was higher at lower O(2) concentrations and
      inhibitors of hypoxic injury, fructose and glycine (10 mM), strongly decreased NO
      induced injury. Upon addition of spermineNONOate, the cytosolic Na(+)
      concentration rapidly increased. The increase in sodium depended on the NO/O(2)
      ratio and was paralleled by hepatocyte death. Sodium-free Krebs-Henseleit buffer
      strongly protected from NO-induced injury. SpermineNONOate also increased
      cytosolic calcium levels but the Ca(2+) chelator quin-2-AM did not diminish cell
      injury. These results show that - in analogy to hypoxic injury - a sodium influx
      largely mediates the NO-induced death of cultured hepatocytes. Oxidative stress
      and disturbances in calcium homeostasis appear to be of minor importance for NO
      toxicity to hepatocytes.

PMID- 16797599
TI  - Entanglement of Antarctic fur seals at Bouvetoya, Southern Ocean.
AB  - Entanglements of Antarctic fur seals Arctocephalus gazella were recorded during
      four summers from 1996 to 2002 at the subantarctic island, Bouvetoya. Rates of
      entanglement varied between 0.024% and 0.059%. These rates are low for a pinniped
      population and might be because of the geographic isolation of the haulout site.
      An apparent decrease in the levels of entanglement over the course of the study
      was likely due, at least in part, to the removal of entanglements by observers.
      At least two-thirds of entangling materials were generated by fishery sources.
      Since there is no known local source of anthropogenic marine pollution, seals
      become entangled either in waters distant from the island, or when materials
      drift into local waters. Significantly more subadults were found entangled than
      expected from the postulated population age class distribution.

PMID- 16797600
TI  - Ideal width of transects for monitoring source-related categories of plastics on
      beaches.
AB  - Although there is a consensus on the necessity of monitoring solid wastes
      pollution on beaches, the methods applied vary widely. Therefore, creating,
      testing and recommending a method that not only allows comparisons of places and
      periods, but also the detection of source signals, will be important to reach the
      objectives of the source-prevention principle. This will also allow the
      optimisation of time, resources, and processing of samples and data. A
      classification of the items found into specific categories was made according to
      their most probable source/use (fisheries, food packaging, hazardous,
      sewage/personal hygiene, beach user, general home). This study tested different
      widths of sampling transects to be used in the detection of plastics
      contamination on beaches, until all the categories were significantly
      represented. Each transect had its total width (50m) sub-divided into eight
      intervals of 0-2.5m; 2.5-5m; 5-10m; 10-15m; 15-20m; 20-30m; 30-40m; and 40-50m.
      The accumulated number of categories in the 50m (up to 2.5m; up to 5m and so on)
      was used to determine the minimal width necessary to qualitatively characterize
      the area regarding plastics contamination. The diversity of the categories was
      directly related to the area of the sampling transect. These results indicate
      that a significant increase in the number of categories in the first intervals
      tend to stabilize from 15-20m onwards.

PMID- 16797601
TI  - Assessment of polycyclic aromatic hydrocarbon input to urban wetlands in relation
      to adjacent land use.
AB  - The relationship between polycyclic aromatic hydrocarbons (PAHs) in wetland
      surface sediments and adjacent land use was assessed in the Elizabeth River, VA,
      an urbanized sub-estuary of the Chesapeake Bay. Significant differences (p<0.05)
      in surface sediment PAH concentration between sites indicated adjacent land use
      had a substantial influence on PAH concentration in wetland sediments. Wetlands
      adjacent to parking lots and petroleum industrial sites exhibited the highest PAH
      concentrations of all wetlands examined. Overall, commercial land uses had the
      highest PAH concentrations and automotive sources dominated (52-69%) PAH input to
      wetland surface sediments irrespective of adjacent land use.

PMID- 16797602
TI  - Estimating the number of motor units using random sums with independently thinned
      terms.
AB  - The problem of estimating the numbers of motor units N in a muscle is embedded in
      a general stochastic model using the notion of thinning from point process
      theory. In the paper a new moment type estimator for the numbers of motor units
      in a muscle is denned, which is derived using random sums with independently
      thinned terms. Asymptotic normality of the estimator is shown and its practical
      value is demonstrated with bootstrap and approximative confidence intervals for a
      data set from a 31-year-old healthy right-handed, female volunteer. Moreover
      simulation results are presented and Monte-Carlo based quantiles, means, and
      variances are calculated for N in{300,600,1000}.

PMID- 16797603
TI  - Letter to the editor.

PMID- 16797604
TI  - Spectral analysis of laser Doppler skin blood flow oscillations in human
      essential arterial hypertension.
AB  - The aim of this study was to investigate whether human essential arterial
      hypertension (EHT) is associated with modification of the skin blood flowmotion
      (SBF), which could be a sign of skin microcirculatory impairment. Forearm skin
      perfusion was measured by laser Doppler flowmetry (LDF) in conventional perfusion
      units (PU) before and after ischemia in 20 middle-age newly diagnosed EHT
      untreated patients, in 20 middle-age long standing EHT treated patients and in 30
      age and sex matched healthy normotensive subjects (NS). Power spectral density
      (PSD) of SBF total spectrum (0.009-1.6 Hz), as well of five different frequency
      intervals (FI), each of them related to endothelial (0.009-0.02 Hz), sympathetic
      (0.02-0.06 Hz), myogenic (0.06-0.2 Hz), respiratory (0.2-0.6) or cardiac (0.6
      1.6) activity, was also measured in PU(2)/Hz before and after ishemia, using
      Fourier analysis of LDF signal. The three studied groups did not differ in basal
      and post-ischemic skin perfusion or in basal SBF parameters considered. However,
      while a significant post-ischemic increase in PSD of total spectrum SBF (P <
      0.001) and of its different FI, with the only exception of respiratory FI, was
      observed in NS, a significsnt post-ischemic increase in PSD was observed only for
      total spectrum (P < 0.01) and for endothelial FI (P < 0.001) in newly diagnosed
      EHT patients and only for myogenic FI (P < 0.05) in long standing EHT patients.
      These findings suggest that the mechanisms which mediate the post-ischemic
      increment of SBF are perturbed earlier in human EHT than the mechanisms which
      mediate the skin post-ischemic hyperaemia. The same findings also suggest that
      the impairment of the endothelial mechanism involved in SBF control occurs by the
      time in the course of EHT.

PMID- 16797605
TI  - Pigment epithelium-derived factor (PEDF) prevents diabetes- or advanced glycation
      end products (AGE)-elicited retinal leukostasis.
AB  - Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of
      angiogenesis in the mammalian eye, suggesting that PEDF may protect against
      proliferative diabetic retinopathy. However, a role for PEDF in early diabetic
      retinopathy remains to be elucidated. Leukocyte adhesion to retinal capillary
      endothelium (leukostasis) is a critical event in early diabetic retinopathy,
      whose process is mainly mediated by intercellular adhesion molecule-1 (ICAM-1).
      We investigated here whether PEDF could prevent diabetes- or advanced glycation
      end products (AGE)-elicited retinal leukostasis by suppressing ICAM-1 expression.
      Immunohistochemistry of 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress
      marker, showed intense staining in the nuclei of cells in the inner and outer
      plexiform layers of streptozotocin-induced diabetic rat retinas. Administration
      of PEDF or pyridoxal phosphate, an AGE inhibitor, decreased retinal levels of 8
      OHdG and subsequently suppressed ICAM-1 gene expression and retinal leukostasis
      in diabetic rats. Further, intravenous administration of AGE to normal rats
      increased ICAM-1 gene expression and retinal leukostasis, which were blocked by
      PEDF. PEDF also inhibited the AGE-induced T cell adhesion to microvascular
      endothelial cells by suppressing ICAM-1 expression. These results demonstrated
      that PEDF inhibited diabetes- or AGE-elicited retinal leukostasis by suppressing
      ICAM-1. Our present study suggests that PEDF may play a protective role against
      early diabetic retinopathy by attenuating the deleterious effect of AGE.

PMID- 16797606
TI  - Analysis of DNA double-strand break repair pathways in mice.
AB  - During the last years significant new insights have been gained into the
      mechanism and biological relevance of DNA double-strand break (DSB) repair in
      relation to genome stability. DSBs are a highly toxic DNA lesion, because they
      can lead to chromosome fragmentation, loss and translocations, eventually
      resulting in cancer. DSBs can be induced by cellular processes such as V(D)J
      recombination or DNA replication. They can also be introduced by exogenous agents
      DNA damaging agents such as ionizing radiation or mitomycin C. During evolution
      several pathways have evolved for the repair of these DSBs. The most important
      DSB repair mechanisms in mammalian cells are nonhomologous end-joining and
      homologous recombination. By using an undamaged repair template, homologous
      recombination ensures accurate DSB repair, whereas the untemplated nonhomologous
      end-joining pathway does not. Although both pathways are active in mammals, the
      relative contribution of the two repair pathways to genome stability differs in
      the different cell types. Given the potential differences in repair fidelity, it
      is of interest to determine the relative contribution of homologous recombination
      and nonhomologous end-joining to DSB repair. In this review, we focus on the
      biological relevance of DSB repair in mammalian cells and the potential overlap
      between nonhomologous end-joining and homologous recombination in different
      tissues.

PMID- 16797607
TI  - Are you always on my mind? A review of how face perception and attention
      interact.
AB  - In this review we examine how attention is involved in detecting faces,
      recognizing facial identity and registering and discriminating between facial
      expressions of emotion. The first section examines whether these aspects of face
      perception are "automatic", in that they are especially rapid, non-conscious,
      mandatory and capacity-free. The second section discusses whether limited
      capacity selective attention mechanisms are preferentially recruited by faces and
      facial expressions. Evidence from behavioral, neuropsychological, neuroimaging
      and psychophysiological studies from humans and single-unit recordings from
      primates is examined and the neural systems involved in processing faces, emotion
      and attention are highlighted. Avenues for further research are identified.

PMID- 16797608
TI  - Neural systems for recognition of familiar faces.
AB  - Immediate access to information about people that we encounter is an essential
      requirement for effective social interactions. In this manuscript we briefly
      review our work and work of others on familiar face recognition and propose a
      modified version of our model of neural systems for face perception with a
      special emphasis on processes associated with recognition of familiar faces. We
      argue that visual appearance is only one component of successful recognition of
      familiar individuals. Other fundamental aspects include the retrieval of "person
      knowledge" - the representation of the personal traits, intentions, and outlook
      of someone we know - and the emotional response we experience when seeing a
      familiar individual. Specifically, we hypothesize that the "theory of mind"
      areas, that have been implicated in social and cognitive functions other than
      face perception, play an essential role in the spontaneous activation of person
      knowledge associated with the recognition of familiar individuals. The amygdala
      and the insula, structures that are involved in the representation of emotion,
      also are part of the distributed network of areas that are modulated by
      familiarity, reflecting the role of emotion in face recognition.

PMID- 16797609
TI  - The representation of information about faces in the temporal and frontal lobes.
AB  - Neurophysiological evidence is described showing that some neurons in the macaque
      inferior temporal visual cortex have responses that are invariant with respect to
      the position, size and view of faces and objects, and that these neurons show
      rapid processing and rapid learning. Which face or object is present is encoded
      using a distributed representation in which each neuron conveys independent
      information in its firing rate, with little information evident in the relative
      time of firing of different neurons. This ensemble encoding has the advantages of
      maximising the information in the representation useful for discrimination
      between stimuli using a simple weighted sum of the neuronal firing by the
      receiving neurons, generalisation and graceful degradation. These invariant
      representations are ideally suited to provide the inputs to brain regions such as
      the orbitofrontal cortex and amygdala that learn the reinforcement associations
      of an individual's face, for then the learning, and the appropriate social and
      emotional responses, generalise to other views of the same face. A theory is
      described of how such invariant representations may be produced in a
      hierarchically organised set of visual cortical areas with convergent
      connectivity. The theory proposes that neurons in these visual areas use a
      modified Hebb synaptic modification rule with a short-term memory trace to
      capture whatever can be captured at each stage that is invariant about objects as
      the objects change in retinal view, position, size and rotation. Another
      population of neurons in the cortex in the superior temporal sulcus encodes other
      aspects of faces such as face expression, eye gaze, face view and whether the
      head is moving. These neurons thus provide important additional inputs to parts
      of the brain such as the orbitofrontal cortex and amygdala that are involved in
      social communication and emotional behaviour. Outputs of these systems reach the
      amygdala, in which face-selective neurons are found, and also the orbitofrontal
      cortex, in which some neurons are tuned to face identity and others to face
      expression. In humans, activation of the orbitofrontal cortex is found when a
      change of face expression acts as a social signal that behaviour should change;
      and damage to the orbitofrontal cortex can impair face and voice expression
      identification, and also the reversal of emotional behaviour that normally occurs
      when reinforcers are reversed.

PMID- 16797610
TI  - Retinotopic effects during spatial audio-visual integration.
AB  - The successful integration of visual and auditory stimuli requires information
      about whether visual and auditory signals originate from corresponding places in
      the external world. Here we report crossmodal effects of spatially congruent and
      incongruent audio-visual (AV) stimulation. Visual and auditory stimuli were
      presented from one of four horizontal locations in external space. Seven healthy
      human subjects had to assess the spatial fit of a visual stimulus (i.e. a gray
      scaled picture of a cartoon dog) and a simultaneously presented auditory stimulus
      (i.e. a barking sound). Functional magnetic resonance imaging (fMRI) revealed two
      distinct networks of cortical regions that processed preferentially either
      spatially congruent or spatially incongruent AV stimuli. Whereas earlier visual
      areas responded preferentially to incongruent AV stimulation, higher visual areas
      of the temporal and parietal cortex (left inferior temporal gyrus [ITG], right
      posterior superior temporal gyrus/sulcus [pSTG/STS], left intra-parietal sulcus
      [IPS]) and frontal regions (left pre-central gyrus [PreCG], left dorsolateral pre
      frontal cortex [DLPFC]) responded preferentially to congruent AV stimulation. A
      position-resolved analysis revealed three robust cortical representations for
      each of the four visual stimulus locations in retinotopic visual regions
      corresponding to the representation of the horizontal meridian in area V1 and at
      the dorsal and ventral borders between areas V2 and V3. While these regions of
      interest (ROIs) did not show any significant effect of spatial congruency, we
      found subregions within ROIs in the right hemisphere that showed an incongruency
      effect (i.e. an increased fMRI signal during spatially incongruent compared to
      congruent AV stimulation). We interpret this finding as a correlate of spatially
      distributed recurrent feedback during mismatch processing: whenever a spatial
      mismatch is detected in multisensory regions (such as the IPS), processing
      resources are re-directed to low-level visual areas.

PMID- 16797611
TI  - Deviations in upper-limb function of the less-affected side in congenital
      hemiparesis.
AB  - In the present study we examined upper-limb function of the less-affected side in
      young adolescents with congenital hemiparesis (cerebral palsy: CP). Five
      participants with hemiparetic CP and five control participants performed a
      cyclical reach-and-grasp task with the less-affected hand towards targets placed
      at 60%, 100%, and 140% of the participant's arm-length. Trunk involvement, end
      effector kinematics and activation of the biceps and triceps were examined
      together with several clinical measures. Movements at the less-affected side were
      slower and peak velocity was reached later in the experimental group. Even though
      total trunk involvement was identical in both groups, it was selectively limited
      to forward bending in participants with CP. Elbow amplitudes of these
      participants were smaller for the 60% and 100% arm-length target distances.
      Additionally, participants with CP showed weak positive correlations between
      agonist (triceps) activity and elbow amplitude, suggesting that deficient agonist
      rather than antagonist innervation was responsible for the decreased elbow
      involvement. Especially the more severely affected participants with CP proved to
      compensate their relatively small elbow amplitudes by increased forward bending.
      Collectively, the findings demonstrate deviations in upper-limb control of the
      less-affected body side in congenital hemiparesis.

PMID- 16797612
TI  - Cognitive processes in the development of TOL performance.
AB  - Components of executive function continue to develop through adolescence. There
      is limited knowledge of how these cognitive components impact complex cognitive
      function requiring their integration. This study examines the development of
      response planning, a complex cognitive function, and the contributions of
      selected cognitive processes, including speed of processing, response inhibition,
      and working memory to its development. We tested 100 healthy 8-30 year old
      individuals with a computerized version to the Tower of London (TOL) task and
      cognitive oculomotor tests including the visually guided saccade, oculomotor
      delayed response, and antisaccade tasks. Speed of processing, response
      inhibition, working memory, and TOL performance all demonstrated maturation in
      adolescence. While all processes were correlated with the development of TOL
      performance, antisaccade performance showed the strongest association indicating
      an important role for response inhibition in planning. These results indicate
      that the development of converging cognitive processes in adolescence, including
      response inhibition and working memory, support response planning and may serve
      as a model for the development of performance in other complex problem solving
      tasks.

PMID- 16797613
TI  - The effect of age on involuntary capture of attention by irrelevant sounds: a
      test of the frontal hypothesis of aging.
AB  - The aim of this study was to examine the effects of aging on the involuntary
      capture of attention by irrelevant sounds (distraction) and the use of these
      sounds as warning cues (alertness) in an oddball paradigm. We compared the
      performance of older and younger participants on a well-characterized auditory
      visual distraction task. Based on the dissociations observed in aging between
      attentional processes sustained by the anterior and posterior attentional
      networks, our prediction was that distraction by irrelevant novel sounds would be
      stronger in older adults than in young adults while both groups would be equally
      able to use sound as an alert to prepare for upcoming stimuli. The results
      confirmed both predictions: there was a larger distraction effect in the older
      participants, but the alert effect was equivalent in both groups. These results
      give support to the frontal hypothesis of aging [Raz, N. (2000). Aging of the
      brain and its impact on cognitive performance: integration of structural and
      functional finding. In F.I.M. Craik & T.A. Salthouse (Eds.) Handbook of aging and
      cognition (pp. 1-90). Mahwah, NJ: Erlbaum; West, R. (1996). An application of
      prefrontal cortex function theory to cognitive aging. Psychological Bulletin,
      120, 272-292].

PMID- 16797615
TI  - Episodic memory impairment in Huntington's disease: a meta-analysis.
AB  - Memory dysfunction is an important feature in the clinical presentation of
      Huntington's disease (HD) and may precede the onset of motor symptoms. Although
      several studies have contributed to the quantitative and qualitative description
      of memory impairments in HD, the characterization of episodic memory impairments
      has varied considerably. Whereas most studies report significant impairments on
      free recall tests, performance on recognition tests has been considerably more
      variable, ranging from normal to markedly deficient. This absence of a well
      established recognition memory deficit has led some investigators to attribute
      the memory deficits in HD to a retrieval-based episodic memory impairment. We
      felt that a quantitative review of the literature was needed to better
      characterize these episodic memory impairments. We conducted a meta-analysis to
      assess the magnitude of the recognition memory deficit in HD and to examine it in
      relation to the known deficit in recall. Memory data were provided by 544
      symptomatic HD patients, 224 presymptomatic gene-carriers, and 963 control
      subjects. The overall group comparison between symptomatic patients and controls
      yielded effect sizes of d=1.95 for free recall and d=1.73 for recognition. We
      split the symptomatic group into two subgroups based on their mental status (mild
      and moderate/severe dementia) and both showed significant deficits in recall and
      recognition memory, though recall was more impaired than recognition in the mild
      dementia subgroup. Only slight memory impairment was observed in the
      presymptomatic subjects. The results show that deficits in recognition memory
      must be accounted for in future models of memory impairment in HD.

PMID- 16797614
TI  - Event-related brain potential correlates of emotional face processing.
AB  - Results from recent event-related brain potential (ERP) studies investigating
      brain processes involved in the detection and analysis of emotional facial
      expression are reviewed. In all experiments, emotional faces were found to
      trigger an increased ERP positivity relative to neutral faces. The onset of this
      emotional expression effect was remarkably early, ranging from 120 to 180ms post
      stimulus in different experiments where faces were either presented at fixation
      or laterally, and with or without non-face distractor stimuli. While broadly
      distributed positive deflections beyond 250ms post-stimulus have been found in
      previous studies for non-face stimuli, the early frontocentrally distributed
      phase of this emotional positivity is most likely face-specific. Similar
      emotional expression effects were found for six basic emotions, suggesting that
      these effects are not primarily generated within neural structures specialised
      for the automatic detection of specific emotions. Expression effects were
      eliminated when attention was directed away from the location of peripherally
      presented emotional faces, indicating that they are not linked to pre-attentive
      emotional processing. When foveal faces were unattended, expression effects were
      attenuated, but not completely eliminated. It is suggested that these ERP
      correlates of emotional face processing reflect activity within a neocortical
      system where representations of emotional content are generated in a task
      dependent fashion for the adaptive intentional control of behaviour. Given the
      early onset of the emotion-specific effects reviewed here, it is likely that this
      system is activated in parallel with the ongoing evaluation of emotional content
      in the amygdala and related subcortical brain circuits.

PMID- 16797616
TI  - Evaluation of wireless determination of skin temperature using iButtons.
AB  - Measurements of skin temperatures are often complicated because of the use of
      wired sensors. This is so in field studies, but also holds for many laboratory
      conditions. This article describes a wireless temperature system for human skin
      temperature measurements, i.e. the Thermochron iButton DS1291H. The study deals
      with validation of the iButton and its application on the human skin, and
      describes clinical and field measurements. The validation study shows that
      iButtons have a mean accuracy of -0.09 degrees C (-0.4 degrees C at most) with a
      precision of 0.05 degrees C (0.09 degrees C at most). These properties can be
      improved by using calibration. Due to the size of the device the response time is
      longer than that of conventional sensors, with a tau in water of 19 s. On the
      human skin under transient conditions the response time is significantly longer,
      revealing momentary deviations with a magnitude of 1 degrees C. The use of
      iButtons has been described in studies on circadian rhythms, sleep and cardiac
      surgery. With respect to circadian rhythm and sleep research, skin temperature
      assessment by iButtons is of significant value in laboratory, clinical and home
      situations. We demonstrate that differences in laboratory and field measurements
      add to our understanding of thermophysiology under natural living conditions. The
      advantage of iButtons in surgery research is that they are easy to sterilize and
      wireless so that they do not hinder the surgical procedure. In conclusion, the
      application of iButtons is advantageous for measuring skin temperatures in those
      situations in which wired instruments are unpractical and fast responses are not
      required.

PMID- 16797617
TI  - Development of the BITE Master II and its application to the study of cheese
      hardness.
AB  - Instrumental methods to assess food texture are often used without considering
      parameters relevant to the sensory perception of food texture and without
      considering conditions occurring in the mouth during chewing. The objective of
      this research was to develop a sensory robot capable of closely mimicking the
      human bite and to conduct its preliminary testing with various cheeses.

PMID- 16797618
TI  - Atropine methyl nitrate increases myenteric but not dorsal vagal complex Fos-like
      immunoreactivity in the rat.
AB  - Atropine methyl nitrate (AMN, 0.05, 0.5 and 25 mg/kg) intraperitoneally increased
      Fos-like immunoreactivity (Fos-LI) in the myenteric plexus, but not the dorsal
      vagal complex (DVC, the area postrema (AP), nucleus of the solitary tract (NTS)
      and the dorsal motor nucleus of the vagus (DMV)) in adult, male Sprague-Dawley
      rats. A 3 mg/kg AMN dose decreased intake of 15% sucrose, but failed to increase
      Fos-LI in both locations. In conclusion, the myenteric plexus may play a local
      role in the behavioral response evoked by AMN.

PMID- 16797619
TI  - Cloning and characterization of a theta class glutathione transferase from the
      potato pathogen Phytophthora infestans.
AB  - A glutathione transferase (GST) related to the theta (T) class of enzymes found
      in plants and animals has been cloned from the potato pathogen Phytophthora
      infestans. The cDNA encoded a 25kDa polypeptide termed PiGSTT1 which was
      expressed in E. coli as the native protein. The purified recombinant enzyme
      behaved as a dimer (PiGSTT1-1) and while being unable to catalyse the glutathione
      conjugation of 1-chloro-2,4-dintrobenzene, was highly active as a glutathione
      peroxidase with organic hydroperoxide substrates. In addition to reducing the
      synthetic substrate cumene hydroperoxide, PiGSTT1-1 was shown to be highly active
      toward 9(S)-hydroperoxy-(10E,12Z,15Z)-octadecatrienoic acid=9(S)-HPOT, which is
      formed in potato plants during infection by P. infestans as a precursor of the
      antifungal oxylipin colnelenic acid. An antiserum was raised to PiGSTT1-1 and
      used to demonstrate that the respective enzyme was abundantly expressed in P.
      infestans both cultured on pea agar and during the infection of potato plants.

PMID- 16797620
TI  - Antimicrobial constituents of Scrophularia deserti.
AB  - A study of the chemistry and antibacterial activity of Scrophularia deserti led
      to the isolation of eight compounds, including the metabolite 3(zeta)-hydroxy
      octadeca-4(E),6(Z)-dienoic acid (1). The known compounds ajugoside (2),
      scropolioside B (3), 6-O-alpha-L-rhamnopyranosylcatalpol (4), buddlejoside A(8)
      (5), scrospioside A (6), laterioside (7) and 3R-1-octan-3-yl-3-O-beta-D
      glucopyranoside (8) were also isolated. Compounds 1-3 exhibited moderate
      antibacterial activity against strains of multidrug and methicillin-resistant
      Staphylococcus aureus (MRSA) and a panel of rapidly growing mycobacteria with
      minimum inhibitory concentration (MIC) values ranging from 32 to 128 microg/ml.

PMID- 16797621
TI  - Effect of Fasciola gigantica infection on adrenal and thyroid glands of riverine
      buffaloes.
AB  - Effect of Fasciola gigantica infection on adrenal and thyroid glands was
      investigated using eight male, yearling Murrah buffaloes. The animals were
      randomly assigned to two groups of four buffaloes each (Group-A, infected; Group
      B, non-infected control). Animals of Group-A were orally infected with 1000 F.
      gigantica viable metacercariae, keeping other four animals of Group-B as
      uninfected control. In the infected buffaloes, the clinical signs began appearing
      from 7th week postinfection (p.i.) and eggs were detected in the faeces between
      day 93 and 99 (95.5+/-1.25) postinfection (p.i.). The serum cortisol level,
      revealed a significant (P<0.05) rise during initial stage of the infection,
      followed by a continuous fall from 12th week onward. Peak cortisol level on 10th
      week (13.30+/-2.57ngml(-1)) was associated with eosinophilia (11.0+/-0.95%).
      However, non-infected controls maintained almost uniform cortisol levels (3.97+/
      0.15-5.88+/-0.09ngml(-1)) throughout the period of the study. The pathological
      changes of adrenal glands were correlated with physiological dysfunction of the
      glands. The levels of T(3) and T(4) were significantly (P<0.05-0.01) low from
      14th week onward and were synchronous with in situ migration, growth and
      development of F. gigantica. Significant reduction in the thyroid hormones was
      further supported by histopathological evidence of lymphocytic thyroiditis
      confirming hypothyroidism. A decrease in Hb, PCV, total erythrocyte counts and
      appearance of reticulocytes in the blood of the infected buffaloes suggested
      regenerative anemia, which could partly be due to hypothyroidism.

PMID- 16797622
TI  - Ketosteroids and hydroxyketosteroids, minor metabolites of sugarcane wax.
AB  - Besides beta-sitosterol and stigmasterol, the major steroids of sugarcane, the
      following minor steroids have been isolated and identified from sugarcane wax:
      3,6-diketosteroids, Delta(4)-3-keto steroids, and Delta(4)-6-hydroxy-3-keto
      steroids. Their structures were established by spectroscopic techniques and
      chemical correlations.

PMID- 16797623
TI  - Steryl esters and phenylethanol esters from Syringa komarowii.
AB  - Three new steryl esters and a new phenylethanol ester, together with 22 known
      compounds were isolated from the aqueous ethanolic extract of the whole plants of
      Syringa komarowii. The new compounds were elucidated as stigmastane-3beta,6alpha
      diol 3-O-tetradecanoate (1), stigmastane-3beta,6alpha-diol 3-O-palmitate (2),
      stigmastane-3beta,6alpha-diol 3-O-stearate (3), and 2-(4-hydroxyphenyl)-ethyl
      dotriacontanoate (4) on the basis of extensive spectral data and chemical
      evidences.

PMID- 16797624
TI  - Inhibition of prostaglandin F2alpha synthesis and oxytocin receptor by
      progesterone antagonists in bovine endometrial cells in vitro.
AB  - Oxytocin receptor (OTR) expression is suppressed by progesterone (P4) during the
      luteal phase of the estrous cycle and then it increases at the time of
      luteolysis, but its regulation is still not completely understood. In vitro
      studies to determine the mechanism of action are hindered because OTR
      spontaneously upregulates in vitro and it is impossible to alter expression with
      P4 or estradiol. During recent studies examining the effect of P4 and an
      antagonist (mifepristone) on PG secretion, we found that mifepristone attenuated
      OT-stimulated PG secretion from endometrial epithelial cells. The objective of
      the present study was to determine, whether this effect of mifepristone was due
      to changes in prostaglandin synthesis and/or OTR. A time-course showed that
      mifepristone (5 microM) had no significant effect after 24 h but by 72 h it
      decreased PGF(2alpha) secretion (P<0.01) and abolished the response of the cells
      to OT (P<0.01). The presence or absence of P4 did not affect the response to
      mifepristone. To determine the site of action of mifepristone, cells were
      cultured for 72 h with or without mifepristone and then COX-1 and COX-2 were
      measured by Western blotting and OTR was measured by saturation analysis. The
      results showed that mifepristone did not affect basal or PMA-stimulated
      expression of either COX-1 or COX-2 but did, however, decrease OTR number
      (P<0.05). These data demonstrate that OTR and the response to OT can be
      downregulated in endometrial epithelial cells in vitro via a mechanism involving
      the P4 receptor.

PMID- 16797625
TI  - Structural identification of methyl protodioscin metabolites in rats' urine and
      their antiproliferative activities against human tumor cell lines.
AB  - Methyl protodioscin (MPD), a furostanol saponin, is a preclinical drug shown
      potent antiproliferative activities against most cell lines from leukemia and
      solid tumors. The metabolites of MPD in rats' urine after single oral doses of 80
      mg/kg were investigated in this research. Ten metabolites were isolated and
      purified by liquid-liquid extraction, open-column chromatography, medium-pressure
      liquid chromatography, and preparative high-performance liquid chromatography.
      The structural identification of the metabolites was carried out by high
      resolution mass spectra, NMR spectroscopic methods including (1)H NMR, (13)C NMR
      and 2D NMR, as well as chemical ways. The 10 metabolites were elucidated to be
      dioscin (M-1), pregna-5,16-dien-3beta-ol-20-one-O-alpha-l-rhamnopyranosyl-(1-->2)
      [alpha-l-rhamnopyranosyl-(1-->4)]-beta-d-glucopyranoside (M-2), diosgenin (M-3),
      protobioside (M-4), methyl protobioside (M-5), 26-O-beta-d-glucopyrannosyl(25R)
      furan-5-ene-3beta, 22alpha, 26-trihydroxy-3-O-alpha-l-rhamnopyranosyl-(1-->4)
      beta-d-glucopyranoside(M-6),26-O-beta-d-glucopyranosyl(25R)-furan-5-ene-3beta,26
      dihydroxy-22-methoxy-3-O-alpha-l-rhamnopyranosyl-(1-->4)-beta-d-glucopyranoside
      (M-7), prosapogenin A of dioscin (M-8), prosapogenin B of dioscin (M-9), and
      diosgenin-3-O-beta-d-glucopyranoside (M-10), respectively. M-1 was the main
      urinary metabolite of MPD in rats. Some metabolites showed potent
      antiproliferative activities against HepG2, NCI-H460, MCF-7 and HeLa cell lines
      in vitro.

PMID- 16797626
TI  - Strain differences of neurosteroid levels in mouse brain.
AB  - Neurosteroids, pregnenolone (Preg), dehydroepiandrosterone (DHEA) and their
      sulfates (PregS and DHEAS) are reported to exert their modulatory effects of
      neuronal excitability and synaptic plasticity via amino acid receptors, which
      affect and regulate the learning and memory process, mood, and depression.
      Although the brain levels of these steroids have been reported in rodents, the
      strain differences of the levels of these steroids have not been demonstrated. We
      examined the concentrations of Preg, 17-OH-Preg, DHEA, androstenediol (ADIOL) and
      their sulfates in whole brains from DBA/2, C57BL/6, BALB/c, ddY and ICR mice, the
      genetic backgrounds of which are different. No differences in the brain levels of
      Preg and DHEA were found among the strains. In contrast, PregS levels in DBA/2
      were significantly lower than in the others, while DHEAS concentrations in DBA/2
      were significantly higher than those in other strains. Strain differences were
      found in 17-OH-Preg, ADIOL and 17-OH-PregS but not in ADIOLS levels. The ranges
      of Preg and PregS levels were the highest among the steroids studied. Further, we
      measured serum these steroid levels. Although strain differences were also found
      in serum steroids, correlation study between brain and serum levels revealed that
      brain neurosteroids studied may not come from peripheral circulation. In
      conclusion, this is the first report of demonstrating mammalian brain levels of
      17-OH-Preg, ADIOL, 17-OH-PregS and ADIOLS and the strain differences in
      neurosteroid levels in mice brains. The differences in levels may involve the
      strain differences in their behavior, e.g. aggression, adaptation to stress or
      learning, in mice.

PMID- 16797627
TI  - Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer
      cell line.
AB  - p14(ARF) tumor suppressor protein regulates p53 by interfering with mdm2-p53
      interaction. p14(ARF) is activated in response to oncogenic stimuli but little is
      known of the responses of endogenous p14(ARF) to different types of cellular
      stress or DNA damage. Azidothymidine (AZT) is being tested in several clinical
      trials as an enhancer of anticancer chemotherapy. However, the knowledge of the
      relationship between AZT and cellular pathways, e.g. p53 pathway, is very
      limited. In this study, we show that AZT, cisplatin (CDDP) and docetaxel (DTX)
      all induce unique molecular responses in OVCAR-3 ovarian carcinoma cells carrying
      a mutated p53, while in A2780, ovarian carcinoma and MCF-7 breast carcinoma cells
      with wild type p53, all of these drugs cause similar p53 responses. We found that
      endogenous p14(ARF) protein in OVCAR-3 cells is down-regulated by DTX but induced
      by AZT and a short CDDP pulse treatment. In HT-29 colon carcinoma cells with a
      mutated p53, all treatments down-regulated p14(ARF) protein. Both CDDP and AZT
      increased the expression of p14ARF mRNA in OVCAR-3 cells. Differences in cell
      death induced by these drugs did not explain the differences in protein and mRNA
      expressions. No increase in the level of either c-Myc or H-ras oncoproteins was
      seen in OVCAR-3 cells after AZT or CDDP-treatment. These results suggest that
      p14(ARF) can respond to DNA damage without oncogene activation in cell lines
      without functional p53.

PMID- 16797628
TI  - Dithiocarbamates have a common toxic effect on zebrafish body axis formation.
AB  - We previously determined that the dithiocarbamate pesticide sodium metam (NaM)
      and its active ingredient methylisothiocyanate (MITC) were developmentally toxic
      causing notochord distortions in the zebrafish. In this study, developing
      zebrafish were exposed to isothiocyanates (ITCs), dithiocarbamates (DTCs) and
      several degradation products to determine the teratogenic relationship of these
      chemical classes at the molecular level. All dithiocarbamates tested elicited
      notochord distortions with notochord NOELs from <4 to 40 ppb, while none of the
      ITCs caused notochord distortions with the exception of MITC. Carbon disulfide
      (CS(2)), a common DTC degradate, also caused distortions at concentrations >200
      times the DTCs. Whole mount in situ hybridization of developmental markers for
      collagen (collagen2a1), muscle (myoD), and body axis formation (no tail) was
      perturbed well after cessation of treatment with pyrolidine-DTC (PDTC), dimethyl
      DTC (DMDTC), NaM, MITC, and CS(2). Therefore, distinct albeit related chemical
      classes share a common toxic effect on zebrafish notochord development. To test
      the responsiveness of the distortion to metal perturbation, five metal chelators
      and 2 metals were studied. The membrane permeable copper chelator neocuproine
      (NCu) was found to cause notochord distortions similar to DTC-related molecules.
      DMDTC and NCu treated animals were protected with copper, and collagen 2a1 and no
      tail gene expression patterns were identical to controls in these animals. PDTC,
      NaM, MITC, and CS(2) were not responsive to copper indicating that the chelation
      of metals is not the primary means by which these molecules elicit their
      developmental toxicity. Embryos treated with DMDTC, NaM, and NCu were rescued by
      adding triciaine (MS-222) which abolishes the spontaneous muscle contractions
      that begin at 18 hpf. In these animals, only collagen 2a1 expression showed a
      similar pattern to the other notochord distorting molecules. This indicates that
      the perturbation of no tail expression is in response to the muscle contractions
      distorting the notochord, while collagen 2a1 is associated with the impact of
      these molecules on much earlier developmental processes.

PMID- 16797629
TI  - Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells
      involves a caspase-dependent mechanism with downregulation of nuclear factor
      kappaB.
AB  - Development of chemotherapy resistance and evasion from apoptosis in
      osteosarcoma, a primary malignant bone tumor, is often correlated with
      constitutive nuclear factor-kappaB (NF-kappaB) activation. Here, we investigated
      the ability of a polyphenolic fraction of green tea (GTP) that has been shown to
      have antitumor effects on various malignant cell lines to inhibit growth and
      induce apoptosis in human osteosarcoma SAOS-2 cells. Treatment of SAOS-2 cells
      with GTP (20-60 microg/ml) resulted in reduced cell proliferation and induction
      of apoptosis, which correlated with decreased nuclear DNA binding of NF
      kappaB/p65 and lowering of NF-kappaB/p65 and p50 levels in the cytoplasm and
      nucleus. GTP treatment of cells reduced IkappaB-alpha phosphorylation but had no
      effect on its protein expression. Furthermore, GTP treatment resulted in the
      inhibition of IKK-alpha and IKK-beta, the upstream kinases that phosphorylate
      IkappaB-alpha. The increase in apoptosis in SAOS-2 cells was accompanied with
      decrease in the protein expression of Bcl-2 and concomitant increase in the
      levels of Bax. GTP treatment of SAOS-2 cells also resulted in significant
      activation of caspases as was evident by increased levels of cleaved caspase-3
      and caspase-8 in these cells. Treatment of SAOS-2 cells with a specific caspase-3
      inhibitor Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO) and general caspase inhibitor N
      benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) rescued SAOS
      2 cells from GTP-induced apoptosis. Taken together, these results indicate that
      GTP is a candidate therapeutic for osteosarcoma that mediates its
      antiproliferative and apoptotic effects via activation of caspases and inhibition
      of NF-kappaB.

PMID- 16797630
TI  - Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH
      SY5Y neuroblastoma cells.
AB  - Mitochondrial oxidative stress plays important roles in aging and age-related
      degenerative disorders. The newly identified mitochondrial thioredoxin (mtTrx;
      Trx2) is a key component of the mitochondrial antioxidant system which is
      responsible for the clearance of reactive intermediates and repairs proteins with
      oxidative damage. Here, we show that in cultured SH-SY5Y human neuroblastoma
      1cells, overexpression of mtTrx inhibited apoptosis and loss of mitochondrial
      membrane potential induced by a chemical oxidant, tert-butylhydroperoxide (tBH).
      The effects of calcium ionophore (Br-A23187) were not affected by mtTrx,
      suggesting the protection was specific against oxidative injury. The
      mitochondrial glutathione pool was oxidized by tBH, and this oxidation was not
      inhibited by increased mtTrx. Consequently, the antioxidant function of mtTrx is
      not redundant, but rather in addition, to that of GSH. Mutations of Cys90 and
      Cys93 to serines rendered mtTrx ineffective in protection against tBH-induced
      cytoxicity. These data indicate that mtTrx controls the mitochondrial redox
      status independently of GSH and is a key component of the defensive mechanism
      against oxidative stress in cultured neuronal cells.

PMID- 16797631
TI  - Trimethyltin-induced apoptosis is associated with upregulation of inducible
      nitric oxide synthase and Bax in a hippocampal cell line.
AB  - Trimethyltin (TMT) produces selective neuronal degeneration in the central
      nervous system (CNS), in which the hippocampus is the most sensitive area. Since
      previous studies have been conducted in either non-neural cells or mixed primary
      cultures, an immortalized hippocampal neuronal cell line (HT-22 cell) was used to
      assess the mechanism and mode of death produced by TMT. The compound produced a
      time- and concentration-dependent apoptotic death that was caspase-mediated.
      Excessive generation of reactive oxygen species (ROS) and subsequent reduction of
      mitochondrial membrane potential (DeltaPsim) were involved in the cytotoxicity.
      Scavenging of ROS by a free radical trapping agent or inhibition of the
      mitochondrial permeability transition (MPT) pore significantly reduced cell
      death. Additionally, TMT increased expression of inducible nitric oxide synthase
      (iNOS) by activation of the redox-sensitive transcription factor NFkappaB.
      Pharmacologic inhibition studies showed that the iNOS-mediated NO generation
      increased expression of Bax and then mitochondrial-mediated apoptosis. It was
      concluded that excessive ROS generation initiated the apoptotic cell death by
      upregulating iNOS followed by increased Bax expression which then led to loss of
      DeltaPsim and caspase-executed cell death. This study is the first to report in a
      neuronal cell model that TMT stimulates induction of iNOS, which then increases
      cellular levels of reactive nitrogen species (RNS) to initiate apoptotic death.

PMID- 16797633
TI  - Ultrasonic surface crack characterization on complex geometries using surface
      waves.
AB  - The characterization of surface cracks on complex geometries using surface waves
      is investigated numerically and experimentally. The specimen geometry is
      implemented in a finite difference code by approximation of the contour using a
      Cartesian grid. In the experiments the out-of-plane surface displacement is
      measured by means of a heterodyne laser interferometer. Good agreement is shown
      by comparison of the calculated out-of-plane displacement with experimental
      results for both cracked and non-cracked specimens. The crack depth is measured
      down to a size of 0.7 times the surface wavelength using a time delay approach.
      The many Rayleigh pulses propagating after the crack can be separated from the
      other modes by a filtering procedure based on the surface wave propagation
      velocity. Only a detailed analysis of the scattering phenomenon using the
      simulation allows an identification of the transmitted pulse required for crack
      depth measurement. Application of the method to a specimen with a real fatigue
      crack shows a systematical error possibly due to the inclined crack profile.

PMID- 16797632
TI  - Microcystin-RR-induced apoptosis in tobacco BY-2 cells.
AB  - Our previous studies showed that microcystin-RR could induce oxidative damage in
      plant cells as they do with animal cells. However, whether microcystin can induce
      plant cell apoptosis is still unknown. In this study, the morphological changes
      of tobacco BY-2 suspension cells exposed to microcystin-RR were observed under
      light microscopy and transmission electron microscopy, and apoptosis was clearly
      distinguished by intense perinuclear chromatin margination, condensation of
      nuclear chromatin after 6d exposure of 50mg/L (about 50microM) microcystin-RR. We
      also found that microcystin-RR can induce tobacco cell apoptosis in a dose- and
      time-dependent manner with flow cytometry analysis. Our study provides the first
      evidence that microcystins can induce plant cell apoptosis.

PMID- 16797634
TI  - Combined spectral estimator for phase velocities of multimode Lamb waves in
      multilayer plates.
AB  - A novel combined spectral estimate (CSE) method for differentiation and
      estimation the phase velocities of multimode Lamb waves whose wave numbers are
      much close or overlap one another in multiplayer plates is presented in this
      paper, which based on auto-regressive (AR) model and 2-D FFT. Simulated signals
      in brass plate were processed by 2-D FFT and CSE. And experiments are performed
      by using two conventional angle probes as emitter and receiver on the same
      surface of three-layered aluminum/xpoxy/aluminum plates, which include
      symmetrical and unsymmetrical plates. The multimode Lamb waves are excited in
      these laminates, and the received signal is processed by 2-D FFT and CSE,
      respectively. The results showed that the phase velocities of multimode signals
      whose wave numbers are much closed cannot be differentiated by 2-D FFT, but CSE
      has strong spatial resolution. Compared the measured phase velocities with the
      theoretical values, the error is smaller than 2% on the whole. It promises to be
      a useful method in experimental signals processing of multimode Lamb waves.

PMID- 16797635
TI  - Design and modeling of inversion layer ultrasonic transducers using LiNbO3 single
      crystal.
AB  - Using inversion domain engineering controlled by heating temperature, the
      LiNbO(3) (LNO) piezoelectric plate with both odd and even-order thickness
      extensional modes can be excited simultaneously. Therefore, the inversion layer
      ultrasound transducer is expected to be capable of operating over a wider
      frequency range. In this paper, the electrical impedance and the acoustic
      characteristics of LiNbO(3) (LNO) inversion layer transducer have been studied by
      finite element modeling (FEM). The transducer designed for this study uses a 36
      degrees rotated Y-cut LiNbO(3) thin plate with an active element thickness of
      approximately 100 microm. First the electrical and elastic properties of the 36
      degrees rotated Y-cut LNO were obtained by transforming a basic piezoelectric
      matrix for Z-cut LNO. In order to validate the FEM using the transformed
      properties several pieces of pure and 50% inversion layer LNO were tested on the
      electrical impedance analyzer. The modeled impedance characteristics were
      consistent with the measured data. Next the model was used to design 50-60 MHz
      transducers using pure and 30% inversion LNO. Two lambda/4 matching layers and a
      Tungsten loaded epoxy backing were used in these designs. The modeled results
      show that an over 90% bandwidth transducer can be made with proper matching and
      30% inversion layer.

PMID- 16797636
TI  - Ultrasonic monitoring of yoghurt formation by using AT-cut quartz: lighting of
      casein micelles interactions process during the acidification.
AB  - The behavior of weak gels during their formation singularly attracts attention of
      dairy products factories. In our study we investigate acidified pre-heated milk
      gels formation that are fairly often used to product yoghurts. The gel formation
      requires a tight control of the first step of micelles modification process and
      the kinetics reaction parameters. The most current rheological parameters used to
      achieve the monitoring are the storage G' and the loss G'' shear moduli and the
      gelation time. The study of these parameters is commonly performed at very low
      frequencies (1 Hz). Our technique uses a 6 MHz AT-cut quartz crystal immersed in
      an acidified milk solution kept at a constant temperature. This method is
      singularly effective to ensure a complete and a reliable follow-up of the
      viscoelastic parameters of casein gels. A suitable new model enables a complete
      follow-up of the micelles evolution from the viscoelastic properties. The
      experimental results of the G' and G'' moduli versus temperature and versus
      glucono-delta-lactone (GDL) added to milk are analyzed. In order to understand
      the micelles modifications, an analysis of the viscoelastic evolution try to
      explain the validity of the various models of micelles modification. In addition
      a new accurate kinetics characteristic time is proposed. This time corresponds to
      the moment for which the elastic effect of material becomes significant. From the
      kinetics study of casein gels at various temperatures, the Arrhenius relationship
      and a modified Flory-Stockmayer relationship give us access to the activation
      energy. By using the proposed technique and the suitable models developed, the
      structure thus quality of dairy products may be better controlled.

PMID- 16797637
TI  - Ultrasonic characterisation of flour-water systems: a new approach to investigate
      dough properties.
AB  - The viscoelastic properties of dough are of great interest in the baking industry
      as they affect the quality of the final product. In this work, the viscoelastic
      properties of dough were investigated using ultrasonic techniques and then
      compared with traditional methods. It has been shown that ultrasonics provides a
      non-destructive, rapid and low cost technique for the measurement of physical
      food characteristics. A common protocol for dough preparation was used for each
      type of measurement. Experimental results on more than 30 different flour quality
      and dough processing were presented. The measurements were correlated and
      compared with traditional dough quality tests. In addition, the capability of
      ultrasound measurements for discriminating flours for different purposes was also
      studied, showing the potential of ultrasound as an alternative measurement method
      to discriminate types of flours for different purposes.

PMID- 16797638
TI  - Application of high intensity air-borne ultrasound for debubbling liquid coating
      layers.
AB  - In the coating processes, the formation of bubbles and microbubbles is relatively
      frequent inside the coating layer. Such bubbles, which are formed as a
      consequence of air retention, are difficult to remove and specifically in high
      speed (quick-drying) industrial application where they cause permanent
      imperfections in the homogeneity of the layer. High-intensity air-borne
      ultrasound may represent a clean means to improve homogenization by quickly
      breaking the bubbles just when they are formed inside the coating film. This
      paper deals with the direct application of air-borne high-intensity ultrasonic
      radiation at a frequency of about 21 kHz over coating layers just immediately
      they have been deposited over wood substrates. Such novel process has been
      implemented and experimentally studied at laboratory and semi-industrial stages.

PMID- 16797639
TI  - 3D analysis of interaction of Lamb waves with defects in loaded steel plates.
AB  - The objective of the research presented here is the investigation of the
      interaction of guided waves with welds, defects and other non-uniformities in
      steel plates loaded by liquid. The investigation has been performed using
      numerical simulation for 2D and 3D cases by the finite differences method, finite
      element method and measurement of 3D distributions of acoustic fields.
      Propagation of the S(0) mode in a steel plate and its interaction with non
      uniformities was investigated. It was shown that using the measured leaky wave
      signals in the water loading of the steel plate and by application of signal
      processing, the 3D ultrasonic field structure inside and outside of the plate can
      be reconstructed. The presence of leaky wave signals over the defect caused by
      the mode conversion of Lamb waves has been proved using the numerical modelling
      and experimental investigations. The developed signal and data processing enables
      to visualise dynamics of ultrasonic fields over the plate, and also to estimate
      spatial positions of defects inside the steel plates.

PMID- 16797640
TI  - Hypersonic velocity measurement using Brillouin scattering technique. Application
      to water under high pressure and temperature.
AB  - This paper presents recent improvement on sound velocity measurements under
      extreme conditions, illustrated by the hypersonic sound velocity measurements of
      water up to 723 K and 9 GPa using Brillouin scattering technique. Because water
      at high pressure and high temperature is chemically very aggressive, these
      experiments have been carried out using a specific experimental set-up. The
      present data should be useful to better constrain the water equation of state at
      high density. This new development brings high-quality elastic data in a large
      pressure/temperature domain, which may afterwards benefit the understanding of
      many other fields as nonlinear acoustics, underwater sound, or physical acoustics
      from a more general point of view.

PMID- 16797641
TI  - Pulsed Rayleigh wave scattered at a surface crack.
AB  - This paper investigates Rayleigh wave interaction with machined slots on flat
      aluminium blocks to simulate surface breaking cracks. Using a finite element
      method, Rayleigh wave scattering by narrow slots of varied depth ranging from 0.5
      mm to 20 mm is calculated. Pulsed wideband Rayleigh waves with a centre frequency
      of 590 kHz and -6 dB bandwidth of 520 kHz is considered. Reflection and
      transmission coefficients are calculated and compare well with the published
      literature. We and other workers have reported enhancement of the measured
      amplitude or particle velocity of an apparent Rayleigh wave close to a surface
      defect. In this paper, it is found that the predicted enhancement of in-plane
      components of particle velocities close to a crack is significantly higher than
      that of the out-of-plane components of particle velocities which appears to be
      mainly due to the mode-converted surface skimming longitudinal wave from the
      crack that has mainly in-plane components near the sample surface. The
      enhancement of the in-plane particle velocity will be observed regardless of the
      type of in-plane sensitive ultrasonic detector used. The explanation of the
      discrepancy of the reflection and transmission coefficients obtained by pulsed
      and narrow band or pseudo continuous Rayleigh waves is discussed. The later
      arriving Rayleigh waves from reverberation along the inside of the crack surface
      are observed, as has been previously reported by other workers, and this may also
      be used to gauge slot depth.

PMID- 16797642
TI  - Nondestructive testing in human teeth using a leaky Lamb wave device.
AB  - A Lamb wave interdigital transducer mounted on a layered substrate composed of
      two plates, a thin piezoelectric ceramic plate and an acrylic plate, operating at
      a liquid-solid boundary, is investigated for ultrasonic nondestructive testing of
      the layer thickness in human teeth. A higher-order mode having a phase velocity
      higher than the longitudinal wave velocity in the human teeth can be used for
      nondestructive testing. In the combination of the two layers, the fourth mode of
      leaky Lamb wave is most favorable for a frequency-controllable radiation angle of
      an ultrasound beam into a water layer as an acoustic coupler. In the
      configuration of an acoustic delay line, the layer-thickness measurement in vivo,
      evaluated from the time interval between two reflected ultrasound echoes, is
      successfully realized under a thin water layer as the acoustic coupler.

PMID- 16797644
TI  - Diffraction aperture non-ideal behaviour of air coupled transducers array
      elements designed for NDT.
AB  - Air coupled piezoelectric ultrasonic array transducers are a novel tool that
      could lead to interesting advances in the area of non-contact laminar material
      testing using Lamb wave's propagation techniques. A key issue on the development
      of such transducers is their efficient coupling to air media (impedance mismatch
      between the piezoelectric material and air is 90 dB or more). Adaptation layers
      are used in order to attain good matching and avoid possible serious signal
      degradation. However, the introduction of these matching layers modify the
      transducer surface behaviour and, consequently, radiation characteristics are
      altered, making the usual idealization criteria (of uniform surface movement)
      adopted for field simulation purposes inaccurate. In our system, we have a
      concave linear-array transducer of 64 elements (electrically coupled by pairs)
      working at 0.8 MHz made of PZ27 rectangular piezoceramics (15 mm x 0.3 mm) with
      two matching layers made of polyurethane and porous cellulose bonded on them.
      Experimental measurements of the acoustic aperture of single excited array
      elements have shown an increment on the geometrical dimensions of its active
      surface. A sub-millimeter vibrometer laser scan has revealed an extension of the
      aperture beyond the supposed physical single array element dimensions. Non
      uniform symmetric apodized velocity surface vibration amplitude profile with a
      concave delay contour indicates the presumed existence of travelling wave
      phenomena over the surface of the outer array matching layer. Also, asymptotic
      propagation velocities around 2500 m/s and attenuation coefficient between 15 and
      20 dB/mm has been determined for the travelling waves showing clear tendencies.
      Further comparisons between the experimental measurements of single array element
      field radiation diagram and simulated equivalent aperture counterpart reveal good
      agreement versus the ideal (uniform displaced) rectangular aperture. For this
      purpose an Impulse Response Method (IRM) has been used.

PMID- 16797643
TI  - Finite element modeling of a microparticle manipulator.
AB  - The contactless movement of microparticles and cells to known locations within a
      fluid volume is of interest in the fields of microtechnology and life sciences. A
      device which can position such inhomogeneities suspended in a fluid at multiple
      locations is described and modeled. The device consists of a thin fluid layer
      contained in a channel etched into a silicon wafer. Waves are excited by a macro
      piezoelectric plate with electrodes on the top and bottom surfaces and, as a
      result, waves propagate into the adjacent fluid. The result is a pressure field
      throughout the fluidic volume. When an inhomogeneity in a fluid is exposed to an
      ultrasonic field the acoustic radiation force results; this is found by
      integrating the pressure over the surface of the particle, retaining second order
      terms, and taking the time average. Thus, due to the presence of a pressure field
      in the fluid in which the particles are suspended, a force field is created. The
      particles are then collected at the locations of the force potential minima. In
      the device described here, the force field is used to position particles into
      lines. The locations of the particles are predicted by using a finite element
      model of the system. The experimental and modeling results, presented here, are
      in good agreement.

PMID- 16797645
TI  - Laser ultrasonic analysis of normal modes generated by a voltage pulse on an AT
      quartz sensor.
AB  - Laser ultrasonic detection is a versatile and highly sensitive tool for the
      observation of surface waves. In the following study, laser ultrasonic detection
      is used for the experimental study of spurious normal vibration modes of a disk
      quartz sensor excited by a voltage pulse. The AT cut crystal (cut of the crystal
      relative to the the main crystallographic axis is 35.25 degrees) is optimal for
      generating mainly thickness-shear vibrations (central frequency 6 MHz) on the
      quartz surface. However, resulting from shear-to-longitudinal and shear-to
      surface mode conversion, and from the weak coupling with the other
      crystallographic axes, other modes (thickness-compressional and bending modes)
      are always present in the plate response. Since the laser vibrometer is sensitive
      to normal displacements, the laser investigation shows waves that can be
      considered as unwanted for the AT quartz used as a shear sensor. The scanned
      three dimensional (3D) amplitude-space-time signals are carefully analysed using
      their representation in three dual Fourier domains (space-time, wave number
      frequency). Results on the transient analysis of the waves, the normal bending
      modes and the dispersion curves are shown.

PMID- 16797646
TI  - Numerical analysis of bulk conical waves in anisotropic cylinders; application to
      stiffness tensor measurement.
AB  - A point source-point receiver technique, based on laser generation and laser
      detection of acoustic waves, allows determination of mechanical properties of an
      anisotropic cylinder. The nature of the material and the geometry of the sample
      give a dispersive behaviour to the diffracted waves and make the acoustic
      signature difficult to interpret. To overpass the intricacies, wave fronts
      (conical waves in the volume and helical waves on the surface) are synthesized
      from signals provided by scanning the primitive line of the cylinder with a laser
      point source. In order to distinguish between direct bulk conical waves and other
      contributions in the acoustic response, some considerations on line surface waves
      and on reflected bulk conical waves are supplied. The identification of the
      stiffness tensor components, based on the inversion of the bulk waves phase
      velocities, is applied to signals simulated for a composite material.

PMID- 16797647
TI  - Action of low frequency vibration on liquid droplets and particles.
AB  - Liquids handling is an important issue in biomedical analysis. Two different
      devices for acoustic manipulation of droplets have already been tested. The first
      one, more classical, uses a high frequency travelling wave and acoustic
      streaming. The second one uses low frequency flexural standing waves in a plate.
      This means of liquid handling is original and easy to implement but the physical
      principle is not obvious. In order to understand more precisely the phenomena
      involved we present new observations on droplet displacement between two planes
      and on the behaviour of a droplet on an inclined vibrating plane with this
      method. The physical principle involved is discussed. The common acoustic
      radiation pressure formulation is expressed via the non-linear theory of sound
      propagation, but in our case the acoustic wavelength is much smaller than the
      height of a water droplet. To get a better understanding of the phenomenon,
      further experiments on the internal liquid flow and behaviour of particles in the
      droplet have been performed. These will be compared with results obtained with
      particles in a thin water-filled vibrating glass tube. The general conclusion is
      that the phenomenon is practical to use for droplet displacement even if its
      complex mechanism is not completely understood.

PMID- 16797648
TI  - Influence of oxygen on the elastic properties of nanocrystalline diamond films
      studied by laser-induced surface acoustic waves.
AB  - Laser-induced surface acoustic waves (SAWs) were used to study the influence of
      oxygen on the elastic properties of nanocrystalline diamond films. A series of
      samples was grown by chemical vapor deposition (CVD) on the (100) plane of p-type
      silicon for 3h under different O(2)/(CH(4)+H(2)) flow ratios from 0% to 8%. The
      elastic properties of these nanocrystalline diamond films were determined from
      the SAW dispersion curves. The maximum frequency realized was about 310 MHz in
      wideband SAW experiments and about 700 MHz using a narrowband mask method with
      several higher harmonics. It was found that the densities of all samples were
      surprisingly high, approaching the ideal value of diamond, whereas the Young's
      modulus increased from 700 to 950 GPa with the addition of oxygen. It is
      concluded that oxygen has a significant positive effect on the elastic properties
      of nanocrystalline diamond.

PMID- 16797649
TI  - A procedure for the efficient selection of piezoelectric ceramics constituting
      high-power ultrasonic transducers.
AB  - The most characteristic narrow-band transducer structure for high-power
      ultrasonic applications is the well known piezoelectric sandwich which is
      reminiscent of the Langevin transducer. Such structure is generally used jointly
      with other components in the construction of industrial high-power transducers.
      One of the main objectives in the design and construction of such high-power
      transducers is to minimize energy losses. To that purpose the selection of the
      piezoelectric ceramic rings forming the sandwich requires clear and specific
      criteria. This paper deals with a numerical and experimental procedure for the
      accurate selection of the piezoelectric rings constituting high-power
      transducers, based on the analysis of the mechanical Q, the frequency and the
      resonance curve. The procedure was experimentally checked by constructing and
      characterizing several transducer structures.

PMID- 16797650
TI  - Rare earth ultrasonic transducer technique research.
AB  - Transducer is the necessary and most important part in the maxonics. New
      applications demand for new transducer, and the renovation of the transducer will
      open a new field for the application of the maxonics. The important method to
      develop new transducer is to find and develop new material. The rare earth giant
      magnetostrictive material Terfenol-D is a new functional material with good
      performance. In this paper, the rare earth ultrasonic transducer was analyzed
      theoretically and devised in four-port method and FEM software ANSYS. A rare
      earth ultrasonic transducer and the transducer with the half wave horn are
      developed, whose performance has shown unique advantage compared with the
      piezoelectric transducer.

PMID- 16797651
TI  - Noise reduction in ultrasonic NDT using undecimated wavelet transforms.
AB  - Translation-invariant wavelet processing is applied to grain noise reduction in
      ultrasonic non-destructive testing of materials. In particular, the undecimated
      wavelet transform (UWT), which is essentially a discrete wavelet transform (DWT)
      that avoids decimation, is used. Two different UWT processors have been
      specifically developed for that purpose, based on two UWT implementation schemes:
      the "a trous" algorithm and the cycle-spinning scheme. The performance of these
      two UWT processors is compared with that of a classical DWT processor, by using
      synthetic grain noise registers and experimental pulse-echo NDT traces. The
      synthetic ultrasonic traces have been generated by an own-developed frequency
      domain model that includes frequency dependence in both material attenuation and
      scattering. The experimental ultrasonic traces have been obtained by inspecting a
      piece of carbon-fiber reinforced plastic composite in which we have mechanized
      artificial flaws. Decomposition level-dependent thresholds, which are suitable
      for correlated noise, are specifically determined in all cases. Soft
      thresholding, Daubechies db6 mother wavelet and the three well-known threshold
      selection rules, Universal, Minimax and SURE, are applied to the different
      decomposition levels. The performance of the different de-noising procedures for
      single echo detection has been comparatively evaluated in terms of signal-to
      noise ratio enhancement.

PMID- 16797652
TI  - Decomposition of an azo dye in aqueous solution by combination of ultrasound and
      visible light.
AB  - The degradation of Acid Orange 7 in aqueous solution has been investigated under
      the irradiation of ultrasound and visible light respectively and simultaneously.
      We have observed that the maximum removal percentage K increases from 4% to 35%
      when the ultrasonic frequency f and power P change from f=20 KHz and P=3 W to f=1
      MHz and P=40 W. On the other hand, the K-value is approximately 3% under the
      irradiation of visible light at 632 nm and 100 mW/mm(2). Under the simultaneous
      irradiation of ultrasound (1 MHz, 40 W) and visible light (632 nm, 100 mW/mm(2)),
      the K-value reaches to approximately 65%, indicating a synergistic effect of
      ultrasound and visible light irradiations. A simple model based on the band gap
      theory and cavitation theory is proposed to explain the synergistic phenomenon.

PMID- 16797653
TI  - PSpice circuital modelling of ultrasonic imaging transceivers including frequency
      dependent acoustic losses and signal distortions in electronic stages.
AB  - A new global circuital model is proposed taking into account some piezoelectric
      and electronic non-ideal aspects of the broadband ultrasonic transceivers used in
      NDT and imaging applications. A quadratic approach, alternative to previous
      linear Spice implementations, is proposed for the frequency dependence of the
      mechanical losses into the piezoelectric sections. Non-ideal frequency-dependent
      electrical effects influencing excitation circuitry performance, and attenuations
      in the propagation medium varying with frequency, are also considered. Results
      calculated, by using PSpice implementations, from conventional and the new
      modelling approaches show how the quadratic option to calculate losses clearly
      reduces the rippled and sharpened waveforms typically originated in many echo
      signals simulations, and which are not observed in real measured responses.
      Experimental waveforms for driving spikes and for echo-signals, in very good
      agreement with responses simulated from the new modelling here proposed, are also
      shown.

PMID- 16797654
TI  - Noise level analysis in buffer rod geometries for ultrasonic sensors.
AB  - This work presents an ultrasonic sensor for on-line batter monitoring with low
      noise design considerations. The density and the compressibility of the batter
      vary as a function of mixing time and are strongly related to the quality of the
      final product. Traditionally, a batter sample of a fixed volume is removed and
      weighted in order to determine its density. This is a time consuming process.
      Benefits to the industry of on-line measuring techniques include better control
      of product quality, improving processing efficiencies and reduction in wastage.
      In this paper low-noise design considerations are accounted for an ultrasonic
      sensor based on a piezoceramic disk mounted between two reference buffer rods of
      acrylic resin to measure the acoustic impedance of the batter. Measuring the
      acoustic impedance changes of the batter its compressibility and density can be
      monitored. Spurious echoes generated at different parts of the buffer rods
      boundary strongly affect accuracy and reliability of the measurements, and are
      considered as noise. The influence of buffer rods geometry on noise level is
      studied using simulations and afterwards justified experimentally. Design aspects
      such as buffer rods length and radius, piezoceramic disk frequency and radius are
      discussed and their influence on noise level is shown. Finally, strategies for
      optimum geometry design of the ultrasonic sensor are given.

PMID- 16797655
TI  - A novel matching network employing surface acoustic wave devices for W-CDMA power
      amplifiers.
AB  - This paper describes a new approach of designing high Q surface acoustic wave
      (SAW) resonators as an inductive element in the matching network for W-CDMA power
      amplifiers (PAs). Spiral inductors based on CMOS/BiCMOS technologies presently
      possess relatively low Q (typically <10) and occupy a considerably large area. In
      order to break through the limitations of the spiral inductors, the authors
      attempt to apply higher Q and wideband SAW resonators employing Cu-grating/15
      degrees YX-LiNbO(3)-substrate structure to the matching network for improved PA
      performance. An analysis was made on SAW resonators in detail, and an SAW
      resonator having a very small capacitance ratio of 3.28 and moderate Q of 147.8
      was developed. After discussing the frequency dependence of the effective
      inductances, SAW resonators, which are used to be as inductive elements in the
      matching networks of PAs, were designed and fabricated. The PA including the
      matching circuit was simulated using the characteristics of the fabricated SAW
      resonators. The result showed that with better shape factor and good out-of
      rejection, the SAW resonators definitely work as an inductive element and could
      replace widely used spiral inductors.

PMID- 16797656
TI  - Preparation of biodiesel with the help of ultrasonic and hydrodynamic cavitation.
AB  - An alkali-catalyzed biodiesel production method with power ultrasonic (19.7 kHz)
      has been developed that allows a short reaction time and high yield because of
      emulsification and cavitation of the liquid-liquid immiscible system.
      Orthogonality experiments were employed to evaluate the effects of synthesis
      parameters. Furthermore, hydrodynamic cavitation was used for biodiesel
      production in comparison to ultrasonic method. Both methods were proved to be
      efficient, and time and energy saving for the preparation of biodiesel by
      transesterification of soybean oil.

PMID- 16797657
TI  - Plasma in sonoluminescing bubble.
AB  - With the new accommodation coefficient of water vapor evaluated by molecular
      dynamics model, the maximum temperature of a sonoluminescing bubble calculated
      with the full partial differential equations easily reaches few tens of thousands
      degrees. Though at this temperature the gas is weakly ionized (10% or less), the
      gas density inside a sonoluminescing bubble at the moment of the bubble's
      flashing is so high that there still forms a dense plasma. The light emission of
      the bubble is calculated by the plasma model which is compared with that by the
      bremsstrahlung (electron-ion, electron-neutral atom) and recombination model. The
      calculation by the two models shows that for the relatively low maximum
      temperature (< 30,000 K) of the bubble, the pulse width is independent of the
      wavelength and the spectrum deviates the black body radiation type; while for the
      relatively high maximum temperature (approximately 60,000 K), the pulse width is
      dependent of the wavelength and the spectrum is an almost perfect black body
      radiation spectrum. The maximum temperature calculated by the gas dynamics
      equations is much higher than the temperature fitted by the black body radiation
      formula.

PMID- 16797658
TI  - Experimental and theoretical determination of 1-3 piezocomposite electroacoustic
      tensor.
AB  - We report the development of two methods for determining the effective
      electroacoustic tensor of 1-3 piezocomposite material, one experimental and one
      theoretical based on homogenization techniques. The main aim was to compare and
      validate the results provided by these approaches. The slowness surfaces of bulk
      wave were computed in the large wavelength domain and were fitted to obtain the
      effective properties of the composite. Model predictions are discussed and
      compared with the Smith's model. The experimental method is an inversion
      technique comparing measurement of transmission coefficient through the
      piezocomposite plate with the simulated coefficient. The accuracy and stability
      of the minimization procedure is discussed. Experimental results obtained from
      two piezocomposite test plates are presented and compared with theory.

PMID- 16797659
TI  - Characterization of TiN coating layers using ultrasonic backward radiation.
AB  - Since ceramic layers coated on machinery components inevitably experience the
      changes in their properties it is necessary to evaluate the characteristics of
      ceramic coating layers nondestructively for the reliable use of coated components
      and the remaining life prediction. To address such a need, in the present study,
      the ultrasonic backward radiation technique is applied to examine the very thin
      TiN ceramic layers coated on AISI 1045 steel or austenitic 304 steel substrate.
      Specifically, the ultrasonic backward radiation profiles have been measured with
      variations in specimen preparation conditions such as coating layer thickness and
      sliding loading. In the experiments performed in the current study, the peak
      angle and the peak amplitude of ultrasonic backward radiation profile varied
      sensitively according to two specimen preparation conditions. In fact, this
      result demonstrates a high possibility of the ultrasonic backward radiation as an
      effective tool for the nondestructive characterization of the TiN ceramic coating
      layers even in such a thin regime.

PMID- 16797660
TI  - Time-varying prediction filter for structural noise reduction in ultrasonic NDE.
AB  - Predominant physical phenomenon in highly scattering materials is the attenuation
      due to dispersion. Therefore, received echo has high frequencies more severely
      attenuated than low frequencies and the structural noise can be modeled as a non
      stationary random process. Most of the proposed techniques for enhancing the flaw
      visibility do not exploit the frequency dependency of the incoming flaw signal,
      assuming homogeneous behaviour of the insonified material. In this work, a new
      technique based on exploiting the non-stationary nature of the incoming UT signal
      is presented. Proposed technique is based on the prediction error obtained with a
      linear and time-varying parametric model of the noise. By this method, when the
      analyzed UT echo has only structural noise, the prediction error is low, however,
      if it contains a flaw, high prediction error occurs because a flaw is a non
      predictable alteration of the material structure. Experiments with stainless
      steel show that this method has an excellent performance on SNR enhancement.

PMID- 16797661
TI  - Comparison of EMT and MST approaches in studying linear acoustics in bubbly
      liquid.
AB  - Two kinds of approaches have been used in literature to study the linear
      acoustics in a liquid-bubble mixture: The effective medium theory approach and
      the multiple scattering theory approach. Theoretical comparisons of mathematical
      formulations and intrinsic relations between these two approaches are given in
      this paper and show their consistency in dealing with the linear acoustics in
      bubbly liquids. Possible applications of these two methods are also generally
      discussed.

PMID- 16797662
TI  - Automatic measurement of the nonlinearity parameter B/A in liquid media.
AB  - Using a 19-MHz focused Gaussian beam generated by a LiNbO(3) plate with an
      inverted polarization layer coupled to an acoustic lens, a method to
      automatically measure the nonlinearity parameter B/A in liquid media is
      presented. A liquid sample is poured into a cylindrical cell set with a glass
      tube on the lens surface. The focusing source emits burst waves. A tungsten rod
      immersed in the sample so that the top surface is normal to the beam axis behaves
      as a perfect reflector. The position of the reflector to maximize the amplitude
      receiving the returned wave determines the sound speed c of the sample. The
      amplitude measurement for the waves returned from the lens-sample interface and
      the reflector surface leads to the determination of the density rho and
      attenuation coefficient alpha, respectively. Then the B/A is finally derived by
      summarizing the measured result of the 38-MHz second harmonic amplitude contained
      in the sound returned back from the reflector, together with rho, c and alpha.
      All these are automatically processed in a short time less than 2 min with the
      performance of computer controlled instruments.

PMID- 16797664
TI  - Air-coupled ultrasonic investigation of multi-layered composite materials.
AB  - Air-coupled ultrasonics is fine alternative for the immersion testing technique.
      Usually a through transmission and a pitch-catch arrangement of ultrasonic
      transducers are used. The pitch-catch arrangement is very attractive for non
      destructive testing and evaluation of materials, because it allows one-side
      access to the object. However, this technique has several disadvantages. It is
      sensitive to specularly reflected and edge waves. A spatial resolution depends on
      a distance between the transducers. A new method for detection and visualisation
      of inhomogeneities in composite materials using one-side access air-coupled
      ultrasonic measurement technique is described. Numerical predictions of Lamb wave
      interaction with a defect in a composite material are carried out and the
      interaction mechanism is explained. Experimental measurements are carried out
      with different arrangements of the transducers. The proposed method enables
      detect delamination and impact type defects in honeycomb materials.

PMID- 16797663
TI  - Kinetic study of silica gels by a new rheological ultrasonic investigation.
AB  - The last decades have seen the development of sol-gel (SG) process currently used
      to develop new materials in a wide range of scientific applications. The SG
      process leads to an oxide macromolecular network through a sol (liquid phase) to
      gel transition. To optimize this process, the control of the kinetic of the
      chemical reaction is required. This kinetic can be deduced from the temporal
      evolution of the viscoelastic parameters. Upto date no complete investigation
      during the SG formation can be achieved by a unique non-destructive technique. In
      this paper, we present an ultrasonic technique to measure the viscoelastic
      parameters (storage G' and loss G'' shear moduli) of the gel material during its
      formation. By using a suitable model which takes into account the mass loading on
      the surface, the viscoelastic parameters of these materials are accurately
      deduced. In order to study the efficiency of this technique, silica gels
      transition is monitored at various formation temperatures and for different
      initial hydrolysis molar ratio (h). In addition, the monitoring is performed at
      different oscillatory shear measurements in the 6-54 MHz frequency range to
      determine a new characteristic time t(vs) corresponding to the moment when the
      material is no more a newtonian liquid. This characteristic time is then compared
      to the gelation time t(g) determined by rheological or acoustic audible range
      methods. Thus the new characteristic time is also a good criterion to
      characterize earlier the SG matrix transition. Our AT-cut quartz technique using
      our model can also be used as a high frequency rheometer for the sol-gel
      materials.

PMID- 16797665
TI  - Acoustic wave propagation in high-pressure system.
AB  - Recently, substantial attention is paid to the development of methods of
      generation of pulsations in high-pressure systems to produce pulsating high-speed
      water jets. The reason is that the introduction of pulsations into the water jets
      enables to increase their cutting efficiency due to the fact that the impact
      pressure (so-called water-hammer pressure) generated by an impact of slug of
      water on the target material is considerably higher than the stagnation pressure
      generated by corresponding continuous jet. Special method of pulsating jet
      generation was developed and tested extensively under the laboratory conditions
      at the Institute of Geonics in Ostrava. The method is based on the action of
      acoustic transducer on the pressure liquid and transmission of generated acoustic
      waves via pressure system to the nozzle. The purpose of the paper is to present
      results obtained during the research oriented at the determination of acoustic
      wave propagation in high-pressure system. The final objective of the research is
      to solve the problem of transmission of acoustic waves through high-pressure
      water to generate pulsating jet effectively even at larger distances from the
      acoustic source. In order to be able to simulate numerically acoustic wave
      propagation in the system, it is necessary among others to determine dependence
      of the sound speed and second kinematical viscosity on operating pressure. Method
      of determination of the second kinematical viscosity and speed of sound in liquid
      using modal analysis of response of the tube filled with liquid to the impact was
      developed. The response was measured by pressure sensors placed at both ends of
      the tube. Results obtained and presented in the paper indicate good agreement
      between experimental data and values of speed of sound calculated from so-called
      "UNESCO equation". They also show that the value of the second kinematical
      viscosity of water depends on the pressure.

PMID- 16797666
TI  - Characterization of surface properties of a solid plate using nonlinear Lamb wave
      approach.
AB  - A nonlinear Lamb wave approach is presented for characterizing the surface
      properties of a solid plate. This characterization approach is useful for some
      practical situations where ultrasonic transducers cannot touch the surfaces to be
      inspected, e.g. the inside surfaces of sealed vessels. In this paper, the
      influences of changes in the surface properties of a solid plate on the effect of
      second-harmonic generation by Lamb wave propagation were analyzed. A surface
      coating with the different properties was used to simulate changes in the surface
      properties of a solid plate. When the areas and thicknesses of coatings on the
      surface of a given solid plate changed, the amplitude-frequency curves both of
      the fundamental waves and the second harmonics by Lamb wave propagation were
      measured under the condition that Lamb waves had a strong nonlinearity. It was
      found that changes in the surface properties might clearly affect the efficiency
      of second-harmonic generation by Lamb wave propagation. The Stress Wave Factors
      (SWFs) in acousto-ultrasonic technique were used for reference, and the
      definitions of the SWFs of Lamb waves were introduced. The preliminary
      experimental results showed that the second-harmonic SWF of Lamb wave propagation
      could effectively be used to characterize changes in the surface properties of
      the given solid plate.

PMID- 16797667
TI  - Propagation of guided elastic waves in 2D phononic crystals.
AB  - The phononic band structure of two-dimensional phononic guides is numerically
      studied. A plane wave expansion method is used to calculate the dispersion
      relations of guided elastic waves in these periodic media, including 2D phononic
      plates and thin layered periodic arrangements. We show that, for any guided
      elastic wave, Lamb or generalised Lamb modes, stop bands appear in the dispersion
      curves, displaying a phononic band structure in both cases.

PMID- 16797668
TI  - Denitrification potential and rates of complex carbon source from dairy effluents
      in activated sludge system.
AB  - A predictive model for the denitrification performance of complex carbon sources
      was proposed based on compositional data. Potential and rates of denitrification
      of single dairy components (lactose, lactate, proteins, fat), as well as binary
      and complex (modelled "process water") mixtures were assessed using test for
      nitrogen uptake rate (NUR). In all experiments, denitrification potential of
      mixtures was found to be significantly higher than the sum of individual
      potentials and denitrification rate with the readily biodegradable moiety of the
      mixtures was similar to the highest rate obtained with individual components
      (lactose or lactate). This work shows that activated sludge acclimated to dairy
      components can be modelled as a single biomass where the maximal anoxic growth
      rate of the biomass limits the denitrification rate with dairy components. As a
      consequence, lactose or lactate determine the maximal denitrification rate
      possible using dairy effluents.

PMID- 16797669
TI  - Considerations on ultra-trace analysis of phthalates in drinking water.
AB  - Stir bar sorptive extraction with liquid desorption followed by large volume
      injection and capillary gas chromatography coupled to mass spectrometry (SBSE
      LD/LVI-GC-MS), had been applied for the determination of ultra-traces of seven
      phthalates (dimethyl phthalate, diethyl phthalate, di-n-butyl phthalate, butyl
      benzyl phthalate, bis(2-ethylhexyl) adipate, bis(2-ethylhexyl) phthalate and
      bis(1-octyl) phthalate) in drinking water samples, which are included in the
      priority lists set by several international regulatory organizations.
      Instrumental calibration under the selected-ion monitoring mode acquisition (LVI
      GC-MS(SIM)), experimental parameters that could affect the SBSE-LD efficiency, as
      well as, the control of the contamination profile are fully discussed. Throughout
      systematic assays on 30 mL water samples spiked at the 0.40 microg/L level, it
      had been established that stir bars coated with 47 microL of
      polydimethylsiloxane, an equilibrium time of 60 min (1,000 rpm) and methanol as
      back extraction solvent, allowed the best analytical performance to monitor
      phthalates in water matrices. From the data obtained, good accuracy and a
      remarkable reproducibility (< 14.8%) were attained, providing experimental
      recovery data in agreement with the theoretical equilibrium described by the
      octanol-water partition coefficients (K(PDMS/W) approximately K(O/W)), with the
      exception of bis(2-ethylhexyl) adipate, bis(2-ethylhexyl) phthalate and bis(1
      octyl) phthalate, for which lower yields were measured. Additionally, a
      remarkable linear dynamic range between 25 and 2,000 ng/L (r(2)>0.99) and low
      detection limits (3-40 ng/L) were also achieved for the seven-phthalates studied.
      The application of the present method to monitor phthalates in tap and bottled
      mineral water samples, allowed convenient selectivity and high sensitivity up to
      1.0 microg/L level, using the standard addition methodology. The proposed method
      showed to be feasible and sensitive with a low sample volume requirement to
      monitor phthalates in drinking water matrices at the ultra-trace level, in
      compliance with international regulatory directives on water quality.

PMID- 16797670
TI  - Fate and removal of polycyclic musks, UV filters and biocides during wastewater
      treatment.
AB  - The fate of polycyclic musks (PCMs) (HHCB, AHTN, ADBI, AHDI, ATII, DPMI), UV
      filters (3-(4-methylbenzylidene) camphor, 4-MBC; octyl-methoxycinnamate, OMC;
      octocrylene, OC; octyl-triazone, OT) and biocides (permethrin, carbendazim)
      during wastewater treatment was studied on a full-scale plant. Average influent
      concentrations of OMC, HHCB, OC, AHTN, 4-MBC and OT were at 20070, 4420, 1680,
      1430, 960 and 720 ng L(-1), respectively. The other PCMs, permethrin and
      carbendazim ranged between < limits of quantification and 670 ng L(-1).
      Concentrations in the water line decreased significantly for most compounds.
      Removal rates for PCMs ranged from 72% to 86%, for UV filters from 92% to >99%
      and were at 92% and 37% for permethrin and carbendazim, respectively. Removal
      during wastewater treatment was mainly driven by sorption onto solids and
      biodegradation. For anaerobic sludge digestion, elimination of PCMs, OMC and the
      biocides was observed.

PMID- 16797671
TI  - An improved route to the synthetic of diphenyl alpha
      (diethoxythiophosphorylamino)methylphosphonates.
AB  - An improved method for the synthesis of Diphenyl alpha
      (diethoxythiophosphorylamino)methylphosphonates under mild conditions is
      described. It consists of the reaction of diethyl thiophosphoramidate (1) with
      triphenyl phosphite (3) and a substituted benzylaldehyde or ketone (2) by a one
      pot procedure with the aid of acetyl chloride.

PMID- 16797672
TI  - Metal availability and uptake by sorghum plants grown in soils amended with
      sludge from different treatments.
AB  - Several factors depending on the sludge, the soil, or the combination of both
      substrates, may affect element availability to plants. In this study, an
      assessment was done of the effect of two sludges obtained by different processes
      (activated sludge and facultative stabilization pond) on heavy-metal availability
      and uptake by sorghum plants in soils with high and low copper contents. Results
      obtained for DTPA-extractable metal indicated higher metal availability in sludge
      amended soils. In addition, sludges caused changes in copper and zinc
      distribution in soil, indicating in most cases a discrete increase in the more
      labile metal forms. However, observed changes did not increase heavy metal
      concentration in plant leaves, indicating that assessment of metal availability
      by a chemical procedure (single extraction or metal fractionation) would not
      permit a good prediction of metal bioavailability. On the other hand, sludge
      application at a rate of 100 t ha(-1) to high-copper agricultural soils would not
      imply greater mobility of this metal on account of a greater sorbing capacity
      provided by the sludges. Such results would indicate that sludges from wastewater
      treatment plants, meeting the standards of heavy metal contents, regardless of
      the process by which they were obtained, may be applied to several kinds of soil,
      even to high-copper soils, with no risk of increasing heavy metal bioavailability
      to phytotoxic levels in the short range.

PMID- 16797673
TI  - Biocatalytic dechlorination of lindane by nano-scale particles of Pd(0) deposited
      on Shewanella oneidensis.
AB  - A new approach for the removal of the pesticide lindane (gamma
      hexachlorocyclohexane or gamma-HCH) makes use of catalytic reduction of HCH to
      benzene over a metal catalyst, namely Pd(0). Since specific surface area plays an
      important role in reactivity of catalysts, this study investigated the use of
      bioPd(0), i.e. nano-scale Pd(0) particles precipitated on the biomass of
      Shewanella oneidensis, for the removal of lindane. It was demonstrated that
      bioPd(0) has catalytic activity towards dechlorination of gamma-HCH, with the
      addition of formate as electron donor, and that dechlorination with bioPd(0) was
      more efficient than with commercial powdered Pd(0). The biodegradable compound
      benzene was formed as reaction product and other HCH isomers could also be
      dechlorinated. Subsequently bioPd(0) was implemented in a membrane reactor
      technology for the treatment of gamma-HCH polluted water. In a fed-batch process
      configuration with formate as electron donor, a removal percentage of 98% of
      gamma-HCH saturated water (10 mg l(-1)) was achieved within 24h. The measured
      chloride mass balance approached the theoretical value. The results of this work
      showed that a complete, efficient and fast removal of lindane was achieved by
      biocatalysis with bioPd(0).

PMID- 16797674
TI  - Assessment of the efficacy of Artemia sp (Crustacea) cysts chorion as barrier to
      chlorpyrifos (organophosphorus pesticide) exposure. Effect on hatching and
      survival.
AB  - In order to reveal the efficacy of the Artemia cysts chorion as barrier to the
      organophosphorus pesticide chlorpyrifos, whole and decapsulated cysts have been
      exposed to 10 mg L(-1) chlorpyrifos in sea water during hydration and hatching
      phase, separately. The concentration of chlorpyrifos in capsulated and
      decapsulated cysts after exposure has been determined in order to elucidate the
      efficacy of chorion as protection to the embryo. The results obtained demonstrate
      the ability of the cysts chorion to obstruct the pass of chlorpyrifos molecules
      through this protection structure. Thus, the concentration of chlorpyrifos in
      exposed decapsulated cysts is higher than in exposed whole cysts. Moreover, after
      removing the chorion of exposed cysts, the concentration of chlorpyrifos in the
      embryo was lower than that of cysts exposed, what would demonstrate the retention
      of chlorpyrifos molecules by the shell. Hatching was not severely affected by
      exposure to the insecticide whereas survival at 44 h of the nauplii exposed to
      chlorpyrifos was significantly different from the controls. Survival of nauplii
      hatched from exposed decapsulated cysts was higher than that from those hatched
      from exposed whole cysts, probably because of the lower vitality of the latter,
      due to depletion of energy reserves during hatching.

PMID- 16797675
TI  - Radiological consequences of the extreme flooding on the lower course of the
      Rhone valley (December 2003, south east France).
AB  - In early December 2003 unusual weather conditions led to major flooding of the
      lower Rhone valley. When it floods, the Rhone carries large masses of solid
      matter in suspension, which potentially includes associated artificial
      (anthropogenic) radioactive contaminants from soil drainage in the catchment area
      and from re-uptake of sedimentary matter that has been contaminated with low
      level radioactive liquid effluents from almost twenty nuclear facilities situated
      along the Rhone valley. A sampling campaign was carried out to investigate the
      level and spread of both sediment mass and associated radioactive contamination
      across the flooded areas. An attempt was made to assess the radiological
      consequences of such an extreme event on contamination of the food chain. Our
      results show that almost 700,000 tons of sediment was transported onto the
      floodplain, of which 80% were coarse and fine sands. These materials transferred
      6660 MBq of 137Cs, 93 MBq of (239+240)Pu, 13 MBq of 238Pu and 204 MBq of 60Co
      over a surface area of 60 km2. More than 90% of deposited sediments are
      concentrated in a 10 km2 area of agricultural soils, and we estimated that 18%
      were plowed into the soil. Nevertheless, the level of activity measured in the
      vegetable crops and milk was not significantly different from the level measured
      in similar samples from regions that were not affected by the December 2003
      floods.

PMID- 16797676
TI  - Effect of Armagnac fractions on human platelet aggregation in vitro and on rat
      arteriovenous shunt thrombosis in vivo probably not related only to polyphenols.
AB  - Previous studies showed that alcohol-free extracts of Armagnac, an oak cask aged
      spirit rich in polyphenols, inhibit human platelet function in vitro and in vivo,
      in an experimental rat arteriovenous shunt thrombosis model and in human healthy
      volunteers. To identify active compounds, we fractionated a freeze-dried extract
      of a 10-year-old Armagnac using successively chloroform, diethyl ether and ethyl
      acetate. The 4 resulting fractions were tested on in vitro human platelet
      aggregation induced by ADP and in vivo on arteriovenous shunt thrombosis after 10
      days oral treatment in rats. Active components were found mainly in fractions 1
      and 3: at the highest concentration (2.4 10(-2) g/l), in vitro ADP-induced
      aggregation was inhibited by 62.7+/-2.1% and 51.2+/-3.8% for F1 and F3,
      respectively, vs 18.9+/-2.4% and 13.9+/-0.4% for fractions 2 and 4 and 33.6+/
      1.5% for the crude extract. There was a significant decrease in thrombus weight
      with the crude extract and all fractions tested after 10 days treatment with 2.5
      mg/kg/day orally, greatest with fraction 1. Characterisation of phenol content
      showed that fraction 1, the most biologically active, was essentially devoid of
      ellagic acid and ellagitannins, the polyphenols initially thought responsible for
      the effect, whereas fraction 2 which was mostly inactive, was the richest in
      polyphenols. CONCLUSION: The antiplatelet and antithrombotic activity of Armagnac
      seems mostly unrelated to polyphenols.

PMID- 16797677
TI  - Decreased ADAMTS13 activity in plasma from patients with thrombotic
      thrombocytopenic purpura.
AB  - The ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I domain
      13) activity was measured by a fluorescence resonance energy transfer (FRET)
      assay in the plasma of healthy volunteers and thrombotic thrombocytopenic purpura
      (TTP) patients to examine its usefulness in the diagnosis of TTP. The plasma
      levels of the ADAMTS13 activity did not show a normal distribution. Its median
      value was 107% (range: 55-170%) in healthy volunteers, but was significantly
      lower in patients with TTP (acquired or familial) and in patients with
      hematopoietic stem cell transplantation. However, it was not significantly lower
      in patients with antiphospholipid syndrome (APS). The ADAMTS13 activity by a FRET
      assay was closely correlated with that by the ADAMTS13 multimer method (r=0.816;
      p<0.001). In 18 patients with less than 10% of ADAMTS13 activity by FRET assay,
      less than 10% of that by multimer assay was 16, thus suggesting a good
      correlation for a low level of ADAMTS13. These findings suggest that the ADAMTS13
      FRET assay correlates well with the ADAMTS13 multimer method and it is therefore
      useful for making a diagnosis of TTP.

PMID- 16797678
TI  - Claudin 1 differentiates endometrioid and serous papillary endometrial
      adenocarcinoma.
AB  - OBJECTIVE: The expression of claudins, the main tight junction proteins involved
      in cell adhesion and carcinogenesis, was studied in endometrioid (type I) and
      seropapillary (type II) endometrial adenocarcinoma. The characteristics and
      possible diagnostic potential of claudin expression pattern were investigated in
      the two cancer types having different prognosis. METHODS: Protein and mRNA
      expression of claudins was evaluated in 17 endometrioid carcinomas and 15
      seropapillary adenocarcinomas by immunohistochemistry and real-time PCR in
      comparison with 38 cases of hyperplasia, normal proliferative and secretory
      endometrium samples. Further, protein expressions used in diagnostics (estrogen
      and progesterone receptors, p53, PCNA and beta-catenin) were also studied.
      RESULTS: In endometrioid carcinoma and hyperplasia low claudin 1 and high claudin
      2 protein contents, whereas in seropapillary adenocarcinoma high claudin 1 and
      low claudin 2 levels were detected. Intense protein expression was noted for
      claudins 3, 4, 5, and 7, without significantly different patterns in carcinoma,
      hyperplasia, secretory, and proliferative endometrium. Real-time PCR results
      confirmed differences in claudin 1 but not claudin 2 mRNA expression, whereas
      some minor discrepancies were observed in comparison with immunohistochemistry
      patterns. CONCLUSION: The two types of endometrial adenocarcinomas were well
      distinguished by claudins 1 and 2 by immunohistochemistry, claudins 3, 4, and 7,
      however, did not prove useful in distinguishing the two entities. The similar
      claudin pattern seen in hyperplasia and endometrioid carcinoma and the
      differences regarding seropapillary adenocarcinoma support the dualistic model of
      endometrial carcinogenesis. The claudin pattern of the two tumor types might
      reflect a different cellular or pathogenetic pathway as well as a different cell
      adhesion behavior explaining the invasive properties.

PMID- 16797679
TI  - Activity of trabectedin (ET-743, Yondelis) in metastatic uterine leiomyosarcoma.
AB  - BACKGROUND: The ongoing search for more effective agents in the treatment of
      uterine leiomyosarcomas is warranted because of the poor prognosis related to
      these tumors. CASE: A case of advanced, recurrent and refractory uterine
      leiomyosarcoma is presented that responded to trabectedin (ET-743) 1.2 mg/m2
      intravenously over 24 h every 3 weeks after failing four prior regimens. A
      durable objective response lasting at least 8 months was documented. CONCLUSION:
      Trabectedin (ET-743) has activity in uterine leiomyosarcoma and warrants further
      investigation.

PMID- 16797680
TI  - Cyclooxygenase 1 and 2 mRNA and protein expression in the Gallus domesticus model
      of ovarian cancer.
AB  - OBJECTIVE: Our purpose was to determine the mRNA and protein expression of
      cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) in ovarian tumors and
      normal ovaries of the hen, which is an excellent model for human ovarian cancer.
      Tissue concentrations of prostaglandin E(2) (PGE2) and PGE2 metabolites were also
      determined. METHODS: Tissue was obtained from ovarian tumor (n = 18) and normal
      ovary (n = 29) of 2- to 4-year old Single-comb White Leghorn hens. Quantitative
      real-time PCR with Sybr Green was used to quantify the mRNA expression of COX-1
      and COX-2, using 18S expression as an internal control for COX normalization.
      Immunohistochemistry using antibodies for COX-1 and COX-2 was used to localize
      protein expression of each isoform in a subset of tumor (n = 5) and normal
      samples (n = 6). For determination of tissue prostaglandin concentration, tissue
      was obtained from ovarian tumor (n = 8) and normal ovary (n = 8). PGE2 and PGE2
      metabolites were measured using competitive enzyme immunoassays (EIAs). RESULTS:
      Our results indicate that COX-1 mRNA expression is significantly higher (P <
      0.05) in ovarian tumor samples compared to normal ovaries while there is no
      significant difference in expression of COX-2 between the samples.
      Immunohistochemistry results support this finding and show COX-1 expression only
      in tumor samples and COX-2 expression unchanged between normal ovary and tumor
      samples. PGE2 levels are significantly higher (P < 0.05) in tumor samples
      compared to normal ovaries, and there is no significant difference in PGE2
      metabolite levels between the samples. CONCLUSION: These findings may implicate
      COX-1 as a suitable target for the prevention or treatment of ovarian cancer.

PMID- 16797681
TI  - The use of bevacizumab to palliate symptomatic ascites in patients with
      refractory ovarian carcinoma.
AB  - OBJECTIVE: To evaluate our experience with the use of bevacizumab in patients
      with heavily pretreated recurrent ovarian carcinoma who have symptomatic ascites.
      METHODS: Four patients were identified who were previously heavily pretreated for
      recurrent ovarian carcinoma. Each had symptomatic ascites and required frequent
      therapeutic paracenteses. Each was treated with bevacizumab with the intent to
      palliate symptomatic ascites. Clinical data including demographic data and
      clinicopathologic variables was abstracted. RESULTS: The four patients
      demonstrated symptomatic relief of ascites. Toxicity was manageable in all
      patients with no grade 3/4 toxicity observed. In addition to symptomatic relief
      of ascites, no therapeutic paracenteses were required after initiation of therapy
      with bevacizumab. CONCLUSIONS: Bevacizumab may be a viable palliative option in
      patients with end stage ovarian carcinoma who have symptomatic ascites.

PMID- 16797682
TI  - Adjuvant radiotherapy and survival outcomes in early-stage endometrial cancer: a
      multi-institutional analysis of 608 women.
AB  - OBJECTIVE: The role of post-operative radiotherapy (RT) in women with early
      stage, low to intermediate risk cancer of the uterine corpus remains
      controversial. The primary objective of this analysis was to evaluate the
      survival outcomes of women with early-stage endometrial cancer treated with
      surgery alone or surgery followed by RT. METHODS: Data from two institutions were
      collected from 1990 to 2003. The 608 eligible women had FIGO stage IA to IIA
      endometrial cancer and underwent primary surgery +/-RT. Univariate and
      multivariate analyses of pertinent variables were performed for the end points of
      disease-free survival (DFS) and overall survival (OS). RESULTS: The median age
      for all women was 64 years. RT was delivered to 133 women (22%). Unfavorable
      histologic grade (P < 0.0001) and stage (P < 0.0001) were significantly more
      prevalent in the adjuvant RT group. At a median follow-up of 5.2 years, 26 pelvic
      (11 vaginal) and 16 distant failures occurred along with 110 deaths (with no
      significant differences between women undergoing surgery alone or followed by
      RT). Adjuvant RT, younger age, and lower stage predicted for improved DFS and OS
      on multivariate analysis. Stratified analysis revealed that adjuvant RT conferred
      a survival benefit in women with stage IC or IIA disease. CONCLUSIONS: Adjuvant
      RT was associated with improved disease-free and overall survival in women with
      higher risk disease. Despite significantly worse disease characteristics among
      women in the adjuvant RT group, the analyzed end points were equivalent among the
      two groups. These findings suggest that adjuvant radiotherapy has a significant
      benefit in reducing mortality and disease progression in early-stage carcinoma of
      the uterine corpus.

PMID- 16797683
TI  - Uterine malignant mixed mullerian tumors should not be included in studies of
      endometrial carcinoma.
AB  - OBJECTIVE: Uterine mixed malignant mullerian tumors (MMMT) have traditionally
      been excluded from clinical trials of endometrial cancer because of a belief that
      they are more correctly included in the sarcoma category. Recently, investigators
      have suggested that uterine MMMTs are actually dedifferentiated epithelial tumors
      and should be treated as such. The current study was undertaken to compare
      outcomes, stage for stage, of uterine MMMT with poor prognosis endometrial
      adenocarcinomas. METHODS: Cases of MMMT from 1996 to 2004 were identified from
      the Tumor Registry after IRB consent was obtained. Retrospective chart review was
      performed. Cases were matched by age, stage, performance status, and surgical
      procedure to controls consisting of grade 3 endometrioid, papillary serous, and
      clear cell endometrial carcinomas from the same time period. Overall survival was
      compared using the Log-Rank test. RESULTS: 68 patients with MMMT were identified.
      23 were excluded due to incomplete records. Patients with MMMT ranged in age from
      51 to 95 years (mean 75.3 years). Approximately half of the patients (53%) had
      stage III or IV disease. Of the controls, 31 (69%) had grade 3 endometrioid, 11
      (24%) papillary serous, and 3 (7%) clear cell carcinoma. Median overall survival
      for all patients with MMMT was significantly shorter than for controls, 18 months
      (range 0.5-72) versus 36 months (range 0.5-123) (P = 0.02). Patients with early
      stage disease (stage I or II) had shorter median survival than controls, 26
      months (range 3-7) vs. 95 months (range 4-123) (P = 0.003). There was no
      difference in median survival when comparing advanced disease (stage III or IV)
      to matched controls, 15 months (range 0.5-70) vs. 19 months (range 0.5-100) (P =
      NS). CONCLUSIONS: Patients with uterine MMMT have a poorer prognosis than those
      patients with high grade epithelial tumors, especially for those with early stage
      disease. Given the discrepancy in survival, these patients should not be included
      in studies of endometrial carcinoma. Further investigations are necessary to
      identify factors to improve survival of these patients.

PMID- 16797684
TI  - Risk factors for anastomotic leak after recto-sigmoid resection for ovarian
      cancer.
AB  - OBJECTIVES: Anastomotic leak after recto-sigmoid (RS) resection for ovarian
      cancer (OC) is a life-threatening complication. Selection of patients for
      protective diverting stomas has been based on observations from the colorectal
      literature. Our objective was to identify primary risk factors for anastomotic
      leak in OC patients undergoing RS resection to better determine who would most
      benefit from protective diversion. METHODS: All patients with OC or primary
      peritoneal cancer who underwent a debulking procedure with RS resection between
      January 1999 and December 2004 were included. Retrospective chart review
      including review of operative notes, pathology reports, and medical records
      including follow-up visits was done. Cases with inadequate postoperative follow
      up, primary end colostomies, or diverting stomas were excluded. RESULTS: 177
      patients form our study cohort. There were a total of 12/177 anastomotic leaks
      (6.8%). The mean time to diagnosis of anastomotic leak was 19 days (range 4-32).
      The leak rate for primary debulking operations was 8.7% (10/115), whereas the
      leak rate in secondary debulking procedures was 3.2% (2/62) (NS, P = 0.22). In
      univariate analysis, only perioperative serum albumin was significantly
      associated with an increased risk of anastomotic leak (mean 3.4 g/dL vs. 2.4
      g/dL, P = 0.002). Based on serum albumin, the leak rate was 6/29 (21%) for levels
      <3.0 g/dL and 2/58 (3.4%) for patients with albumin greater than or equal to 3.0
      g/dL (OR 7.3, 95% CI 1.37-38.87). CONCLUSIONS: Low serum albumin is associated
      with an increased risk of anastomotic leak after RS resection for OC. Patients
      with a low albumin level may benefit from a protective diverting
      colostomy/ileostomy.

PMID- 16797685
TI  - Differential expression profiling of genes in a complete hydatidiform mole using
      cDNA microarray analysis.
AB  - OBJECTIVES: To gain a better understanding of the genes involved in the
      pathogenesis of gestational trophoblastic diseases, we evaluated the genome-wide
      expression levels of genes in complete hydatidiform mole (H-mole) as compared to
      normal placenta using cDNA microarray technique. METHODS: The expression profiles
      of complete H-mole tissues were compared with those of normal placenta using cDNA
      microarray technique. The data obtained from 10,305 human genes were normalized
      by the print-tip-based LOWESS method. Significance analysis of microarray (SAM)
      was used to identify genes with statistically significant changes in expression.
      The expression levels of genes which showed significant differences between
      normal early placenta and complete H-mole tissues were further confirmed by RT
      PCR. RESULTS: A cDNA microarray analysis consisting of 10,305 human genes
      revealed significant changes in the expression of 213 genes, with 91 genes being
      upregulated and 122 being downregulated. SAM revealed significant changes in gene
      expression, including those associated with signal transduction, cell structure,
      transcription, and apoptosis. Further RT-PCR analysis of altered gene expression
      in mole tissues supported the microarray analysis results. We confirmed the
      upregulation of TLE4, CAPZA1, PRSS25, RNF130, and USP1 in complete H-mole
      tissues. Moreover, our study provides the first evidence that ELK3, LAMA3, LNK,
      STAT2, and TNFRSF25 are downregulated in complete H-mole compared to normal early
      placenta tissues. CONCLUSIONS: These findings provide a large body of information
      regarding gene expression profiles associated with complete H-mole tumorigenesis
      and allow the identification of potential targets for tumor prevention or
      therapy.

PMID- 16797686
TI  - Cost-effectiveness of routine vaginal cytology for endometrial cancer
      surveillance.
AB  - OBJECTIVE: To examine the cost-effectiveness of routine vaginal cytology in
      detecting asymptomatic isolated vaginal recurrence during post-treatment
      endometrial cancer surveillance. METHODS: All patients treated for endometrial
      cancer between 7/1/97 and 6/30/2005 were retrospectively identified from the
      tumor registry database. Clinico-pathologic characteristics and surveillance
      testing data were abstracted from medical records. The total number of Pap tests
      performed during surveillance or until the time of recurrence was calculated and
      charges associated with detecting asymptomatic isolated vaginal recurrence
      assigned based on 2005 Pap test costs adjusted retroactively using the consumer
      price index. RESULTS: Three hundred seventy-seven patients met inclusion
      criteria: FIGO Stage I=63.7%, Stage II=10.1%, Stage III=18.8%, Stage IV=7.4%. The
      median follow-up time was 30.4 months. A total of 2,134 Pap tests were collected
      during the study interval (median 5, mean 5.76 samples/patient). Endometrial
      cancer recurred in 61 patients (16.2%); 11 patients (2.9%) had an isolated
      vaginal recurrence. Seven isolated vaginal recurrences were detected by physical
      examination alone, and 2 were detected by interval computed tomography. An
      asymptomatic isolated vaginal recurrence was detected by routine vaginal cytology
      in 2 of 377 patients (0.5%). Detection of each asymptomatic vaginal recurrence
      required 1067 Pap tests, generating 44,049 US dollar in cumulative charges.
      CONCLUSIONS: As a surveillance test for endometrial cancer recurrence, routine
      vaginal cytology is costly, inefficient, and benefits less than 1% of patients.
      Elimination or reduction in the use of vaginal cytology for this purpose offers
      an opportunity for significant cost savings in gynecologic oncology health care
      expenditure.

PMID- 16797687
TI  - Theriogenology and developments in epidemiology: future opportunities?
AB  - The concepts and methods of the different branches of epidemiology, particularly
      clinical epidemiology, have much to offer the discipline of theriogenology. As
      with theriogenology, epidemiologic methods evolve when technological innovation
      enables new approaches to old problems. The recent emergence, from clinical
      epidemiology, of the evidence-based medicine paradigm in human medicine, and the
      associated developments of systematic reviews and meta-analysis, present new
      opportunities for collaboration and synergy between the two disciplines.

PMID- 16797688
TI  - Effect of ghrelin in dry matter intake and energy metabolism in prepartum sheep:
      a preliminary study.
AB  - The objective of this study was to determine the effect of ghrelin on dry matter
      intake and energy metabolites in ewes during the last 10d of gestation. Ewes were
      randomly assigned to either a treatment (n=6) or a control group (n=6). One hour
      after feeding (08:00 and 16:00), ewes in the treated group were given ovine
      ghrelin (3 microg/kg, i.m.) and the control group received an equivalent volume
      of saline. Treatments were continued until lambing. Daily blood samples were
      taken starting at assignment. The principal findings were that: (1) ewes treated
      with ghrelin had a higher dry matter intake only on the first day of treatment;
      (2) treated ewes had lower serum concentrations of non-esterified fatty acids and
      insulin but higher serum concentrations of growth hormone; (3) serum
      concentrations of beta-hydroxy butyrate and cortisol were not different between
      treated and non-treated ewes. In conclusion, treatment with ghrelin affected dry
      matter intake and energy metabolites of pre-partum ewes during the last 10 d of
      pregnancy.

PMID- 16797689
TI  - Synthesis and evaluation of ethylene glycol 3-diethylamino-propionate
      methacrylate as a polymerizable amine coinitiator for dental application.
AB  - OBJECTIVE: The primary objective of this study was to synthesize and characterize
      ethylene glycol 3-diethylamino-propionate methacrylate (EGDPM) as a polymerizable
      coinitiator to replace the commercial amine coinitiator. The 2,2-bis[4-(2-hydroxy
      3-methacryloxypropoxy)phenyl]-propane (Bis-GMA) and triethylene glycol
      dimethylacrylate (TEGDMA) resin mixture was polymerized by camphorquinone/EGDPM
      initiator system under visible light irradiation. The mechanical properties,
      water sorption and solubility of cured samples were also evaluated. METHODS:
      EGDPM was synthesized via Michael-Addition reaction and characterized using FTIR
      and 1H NMR spectroscopy. Photopolymerization kinetics of the dental resin
      mixtures were monitored by real-time IR (RTIR). The mechanical properties of
      cured samples were recorded by dynamic mechanical analyzer (DMA). And the water
      sorption and solubility of cured samples were detected according to ISO 4049.
      RESULTS: Both the double bond conversion and the rate of polymerization of the
      resin mixtures increased as increasing the concentration of EGDPM but were lower
      than that of ethyl-4-dimethylaminobenzoate (EDMAB) and 2-(dimethylamine)ethyl
      methacrylate (DMEM) as a coinitiator at some concentration. When it served as
      diluent, the final double bond conversion was comparable to that of EDMAB, and
      the rate of polymerization was higher than that of DMEM. The modulus and T(g) of
      the cured samples were very close. Water sorption and solubility of the samples
      were almost the same except that of EGDPM as diluent. CONCLUSIONS: EGDPM was
      synthesized by Michael-Addition reaction. It could be used as a potential
      coinitiator but not suitable as diluent for dental composite.

PMID- 16797690
TI  - Kinetic and mechanistic considerations in the gelation of genipin-crosslinked
      gelatin.
AB  - The gelling properties (gel time (t(gel)) and gel strength) of a 10% (w/w)
      gelatin sol were investigated as a function of genipin (GP) concentration (0-15
      mM) and temperature (25-55 degrees C) to discern mechanisms and optimal
      conditions for fixation. Gel time increased with increasing temperature, reached
      a maximum, and then declined as temperature was raised further. By contrast,
      network strength data followed the opposite trend. From the thermal behavior of
      t(gel) and network strength, it was inferred that gelation in the low-temperature
      regime was dominated by hydrogen bonding, while in the high-temperature regime it
      was dominated by covalent crosslinking. At higher temperatures, crosslinking was
      described by an Arrhenius rate law expression, with activation energies between
      63.2 and 67.8 kJ/mol, depending on GP concentration. In the low temperature
      regime, an Arrhenius plot resulted in negative activation energies of -75.8 and 
      64.4 kJ/mol in the presence of 10 and 15 mM GP, respectively. With an increase in
      both GP concentration and temperature, the gelatin network gradually shifted from
      being dominated by hydrogen bonds (physical crosslinks) to covalent crosslinking
      (chemical crosslinks).

PMID- 16797691
TI  - The adhesive strength of non-spherical particles mediated by specific
      interactions.
AB  - The specific adhesive interaction between a non-spherical particle and a cell
      layer under a linear shear flow is analyzed. The effect of the characteristic
      particle size, expressed in terms of the volume V, and shape, expressed in terms
      of the aspect ratio gamma, on the adhesive strength is investigated. It is shown
      that for a fixed shape, there exists an optimal volume V(opt) for which the
      adhesive strength has a maximum. A surprisingly accurate relationship has been
      derived between the optimal volume V(opt) and the ratio microS/m(r) (wall shear
      stress to the receptors surface density) having the form
      V(opt)=alpha(m(r)/microS)(beta). Also, oblate particles have been shown to adhere
      more effectively to the biological substrate than classical spherical particles
      for the same volume V. As a consequence, non-spherical particles can carry a
      larger amount of drugs and contrast agents than classical spherical particles
      with the same adhesive strength, improving the therapeutic and imaging efficacy.
      The formulae and the procedures described in the present work can guide the
      optimal design of intravascularly injectable micro/nano carriers.

PMID- 16797692
TI  - Biomimetic phosphorylcholine polymer grafting from polydimethylsiloxane surface
      using photo-induced polymerization.
AB  - The biomimetic synthetic phospholipid polymer containing a phosphorylcholine
      group, 2-methacryloyloxyethyl phosphorylcholine (MPC), has improved the surface
      property of biomaterials. Both hydrophilic and anti-biofouling surfaces were
      prepared on polydimethylsiloxane (PDMS) with MPC grafted by surface-initiated
      photo-induced radical polymerization. Benzophenone was used as the
      photoinitiator. The quantity of the adsorbed initiator on PDMS was determined by
      UV absorption and ellipsometry. The poly(MPC)-grafted PDMS surfaces were
      characterized by XPS, ATR-FTIR and static water contact angle (SCA) measurements.
      The SCA on PDMS decreased from 115 degrees to 25 degrees after the poly(MPC)
      grafting. The in vitro single protein adsorption on the poly(MPC)-grafted PDMS
      decreased 50-75% compared to the unmodified PDMS. The surface friction of the
      poly(MPC)-grafted PDMS was lower than the unmodified PDMS under wet conditions.
      The oxygen permeability of the poly(MPC)-grafted PDMS was as high as the
      unmodified PDMS. The tensile property of PDMS was maintained at about 90% of the
      ultimate stress and strain after the poly(MPC) grafting. The surface-modified
      PDMS is expected to be a novel medical elastomer which possesses an excellent
      surface hydrophilicity, anti-biofouling property, oxygen permeability and tensile
      property.

PMID- 16797693
TI  - Biodegradability and biocompatibility of a pH- and thermo-sensitive hydrogel
      formed from a sulfonamide-modified poly(epsilon-caprolactone-co-lactide)
      poly(ethylene glycol)-poly(epsilon-caprolactone-co-lactide) block copolymer.
AB  - A pH- and thermo-sensitive block copolymer was synthesized by adding pH-sensitive
      sulfamethazine oligomers (SMOs) to either end of a thermo-sensitive poly(epsilon
      caprolactone-co-lactide)-poly(ethylene glycol)-poly(epsilon-caprolactone-co
      lactide) (PCLA-PEG-PCLA) block copolymer. The resulting pH- and thermo-sensitive
      SMO-PCLA-PEG-PCLA-SMO block copolymer solution did not form a gel at high pH (pH
      8.0) or at increased temperatures (ca. 70 degrees C), but did form a stable gel
      under physiological conditions (pH 7.4 and 37 degrees C). The degradation rate of
      the pH- and thermo-sensitive block copolymer decreased substantially compared
      with the control block copolymer of PCLA-PEG-PCLA, due to the buffering effect of
      the SMO-PCLA-PEG-PCLA-SMO sulfonamide groups on the acidic monomer-induced rapid
      degradation of PCLA-PEG-PCLA. This suitable sol-gel transition and sustained
      biodegradability of the pH- and thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block
      copolymer resolves two of the major drawbacks associated with thermo-sensitive
      block copolymers, namely premature gelation and rapid degradation. Interestingly,
      SMO-PCLA-PEG-PCLA-SMO showed no evidence of cytotoxicity in vitro. However,
      subcutaneous injection of the pH- and thermo-sensitive block copolymer solution
      (20wt% in PBS at pH 8.0) into Sprague-Dawley (SD) rats resulted in rapid, stable
      gel formation, with the injected hydrogel being completely degraded in vivo in
      just 6 weeks. The injected hydrogel in vivo presented a typical acute
      inflammation within 2 weeks, although chronic inflammation was not observed
      during the first 6-week period. As such, the pH- and thermo-sensitive hydrogel of
      the SMO-PCLA-PEG-PCLA-SMO block copolymer is a suitable candidate for use in drug
      delivery systems and cell therapy.

PMID- 16797694
TI  - Vasomotion in human umbilical and placental veins: role of gap junctions and
      intracellular calcium reservoirs in their synchronous propagation.
AB  - Vasomotion was characterized using human placentae vessel rings; force
      displacement transducers recorded isometric contractions. Umbilical vein rings
      display rhythmic contractions occurring with a frequency of 1.47+/-0.01 min(-1)
      and 274+/-2.2 mg (n=211) of amplitude, which corresponds to 11.1+/-0.4% of the
      maximal KCl contracture. Vasomotion waves were recorded for up to 8 h; their
      amplitude and duration was larger in umbilical veins than arteries or chorionic
      vessels (p<0.001), vasomotion frequency was indistinguishable among these
      vessels. Segments of the umbilical vein closer to the fetus showed larger
      amplitudes and longer-lasting waves. Gap junction blockers, including peptide Gap
      27, 18alpha-glycyrrhetinic acid, hexanol, heptanol or octanol, reduced the
      amplitude but not the frequency of vasomotion; all these drugs, in addition,
      decreased tissue basal tension. The role of intracellular calcium stores was
      evidenced using calcium-free buffer, which reduced oscillation amplitude and
      tissue basal tension. Cyclopiazonic acid increased wave amplitude and tissue
      basal tension, reducing oscillatory frequency. We propose that biological
      oscillators localized in the smooth muscle layer of the umbilical cord, trigger
      vasomotion waves, which are synchronized and propagated via gap junctions;
      internal calcium reservoirs are essential for their maintenance. These myogenic
      oscillations may be relevant for maternal-fetus blood flow and contribute to
      fetal nutrition and development.

PMID- 16797695
TI  - Microarray analysis of BeWo and JEG3 trophoblast cell lines: identification of
      differentially expressed transcripts.
AB  - Trophoblast cell lines are important research tools used as a surrogate for
      primary trophoblast cells in the study of placental function. Because the
      cellular origins of transformed trophoblasts are likely to be diverse, it would
      be of value to understand the unique and shared phenotypes of the cells on a
      global scale. We have compared two widely used cell lines, BeWo and JEG3, by
      microarray analysis in order to identify differentially expressed genes. Results
      indicated that approximately 2700 genes were differentially expressed between the
      cell lines, with principal differences observed in the biological processes of
      response to stress, cell adhesion, signal transduction, and protein and
      nucleobase metabolisms. These data suggest that BeWo and JEG3 cell lines, and
      perhaps other trophoblast cell lines, are sufficiently dissimilar from each other
      such that they will be differentially suited for specific experimental paradigms.

PMID- 16797696
TI  - Role of intracellular stores in the regulation of rhythmical [Ca2+]i changes in
      interstitial cells of Cajal from rabbit portal vein.
AB  - Interstitial cells of Cajal (ICCs) freshly isolated from rabbit portal vein and
      loaded with the Ca(2+)-sensitive indicator fluo-3 revealed rhythmical [Ca(2+)](i)
      changes occurring at 0.02-0.1 Hz. Each increase in [Ca(2+)](i) originated from a
      discrete central region of the ICC and propagated as a [Ca(2+)](i) wave towards
      the cell periphery, but usually became attenuated before reaching the ends of the
      cell. In about 40% of ICCs each rhythmical change in [Ca(2+)](i) consisted of an
      initial [Ca(2+)](i) increase (phase 1) followed by a faster rise in [Ca(2+)](i)
      (phase 2) and then a decrease in [Ca(2+)](i) (phase 3); the frequency correlated
      with the rate of rise of [Ca(2+)](i) during phase 1, but not with the peak
      amplitude. Rhythmical [Ca(2+)](i) changes persisted in nicardipine, but were
      abolished in Ca(2+)-free solution as well as by SK&F96365, cyclopiazonic acid,
      thapsigargin, 2-APB, xestospongin C or ryanodine. Intracellular Ca(2+) stores
      visualised with the low-affinity Ca(2+) indicator fluo-3FF were found to be
      enriched with ryanodine receptors (RyRs) detected with BODIPY TR-X ryanodine.
      Rhythmical [Ca(2+)](i) changes originated from a perinuclear S/ER element showing
      the highest RyR density. Immunostaining with anti-TRPC3,6,7 antibodies revealed
      the expression of these channel proteins in the ICC plasmalemma. This suggests
      that these rhythmical [Ca(2+)](i) changes, a key element of ICC pacemaking
      activity, result from S/ER Ca(2+) release which is mediated via RyRs and IP(3)
      receptors and is modulated by the activity of S/ER-Ca(2+)-ATPase and TRP channels
      but not by L-type Ca(2+) channels.

PMID- 16797697
TI  - T-type Ca2+ channels in sperm function.
AB  - Intracellular Ca2+ regulates many fundamental physiological processes in
      excitable and non-excitable cells. Certainly this is the case of sperm where the
      local concentration of intracellular Ca2+ ([Ca2+]i) is significantly influenced
      by Ca2+ permeable channels present in the cell plasma membrane. Amongst these
      channels, the voltage dependent Ca2+ channels (CaV) of the T-type (CaV3) appear
      to have an eminent role in the acrosome reaction (AR) of some sperm species,
      though they may participate in other important functions like motility and
      capacitation. The AR is an exocytotic event where the acrosome vesicle in the
      posterior region of the head fuses with the plasma membrane. This reaction allows
      sperm to fuse and fertilize the egg. Here we summarize our present knowledge
      regarding CaV3 channels in sperm, show the first direct electrophysiological
      evidence for their presence in maturing mouse sperm and discuss some of the
      relevant unanswered questions.

PMID- 16797698
TI  - T-type Ca2+ channels in non-vascular smooth muscles.
AB  - T-type Ca2+ current has been recorded in smooth muscle myocytes, and associated
      interstitial cells, isolated from the gastro-intestinal tract, urinary bladder,
      urethra, prostate gland, myometrium, vas deferens, lymphatic vessels and airways
      smooth muscle. By contrast, current through such channels has not been recorded
      from other tissues, such as the ureter. Whilst the properties of this Ca2+
      current are similar in most of these cells, with respect to their voltage
      dependence, ion selectivity and response to channel modulators, some differences
      have been recorded, most notably in the gastro-intestinal tract, and may demand a
      reappraisal of how a T-type Ca2+ current is characterised. The functions of such
      a current in different tissues remains uncertain. In most of smooth muscles
      discussed in this review, it is hypothesised that it underlies rhythmic or
      spontaneous electrical activity, especially in concert with other current
      carrying systems, such as Ca2+-activated outward currents. Of equal interest is
      that the T-type Ca2+ channel may be a target for agents that modulate tissue
      function, especially in pathological conditions, or are the site of secondary
      effects of agents used in clinical medicine. For example, T-type Ca2+ channel
      modulators have been proposed to reduce overactive muscular activity in the
      gastro-intestinal or urinary tract, or function as tocolytic agents: and the
      action of volatile anaesthetics on them in airways smooth muscle requires
      consideration in their overall action.

PMID- 16797700
TI  - Molecular pathways underlying the modulation of T-type calcium channels by
      neurotransmitters and hormones.
AB  - Low-voltage-activated T-type calcium channels are expressed in various tissues,
      especially in the brain, where they promote neuronal firing and are involved in
      slow wave sleep and absence epilepsy. While the transduction pathways by which
      hormones and neurotransmitters modulate high-voltage-activated calcium channels
      are beginning to be unraveled, those implicated in T-type calcium channel
      regulation remain obscure. Several neurotransmitters and hormones regulate native
      T-type calcium channels, although some contradictory data have been reported
      depending on the cell type studied. This review focuses on the short-term
      (minutes range) modulation of T-type calcium channels by neurotransmitters and
      hormones and on the roles of G proteins and protein kinases in these modulatory
      effects. Results obtained in different native tissues are discussed and compared
      with the more recent studies of the three cloned T-type calcium channels CaV3.1,
      CaV3.2 and CaV3.3 in expression systems.

PMID- 16797699
TI  - T-type Ca2+ channels in vascular smooth muscle: multiple functions.
AB  - Vascular smooth muscle is a major constituent of the blood vessel wall, and its
      many functions depend on type and location of the vessel, developmental or
      pathological state, and environmental and chemical factors. Vascular smooth
      muscle cells (VSMCs) use calcium as a signal molecule for multiple functions. An
      important component of calcium signaling pathways is the entry of extracellular
      calcium via voltage-gated Ca2+ channels, which in vascular smooth muscle cells
      (VSMCs) are of two main types, the high voltage-activated (HVA) L-type and low
      voltage-activated (LVA) T-type channels. Whereas L-type channels function
      primarily to regulate Ca2+ entry for contraction, it is generally accepted that T
      type Ca2+ channels do not contribute significantly to arterial vasoconstriction,
      with the possible exception of the renal microcirculation. T-type Ca2+ channels
      are also present in some veins that display spontaneous contractile activity,
      where they likely generate pacemaker activity. T-type Ca2+ channel expression has
      also been associated with normal and pathological proliferation of VSMCs, often
      stimulated by external cues in response to insult or injury. Expression of T-type
      channels has been linked to the G1 and S phases of the cell cycle, a period
      important for the signaling of gene expression necessary for cell growth,
      progression of the cell cycle and ultimately cell division. To better understand
      T-type Ca2+ channel functions in VSM, it will be necessary to develop new
      approaches that are specifically targeted to this class of Ca2+ channels and its
      individual members.

PMID- 16797703
TI  - Chronic lymphocytic leukemia patients with a V1-69 gene rearrangement do not have
      inferior survival with respect to patients that express other unmutated V(H)
      genes.
AB  - Recent studies indicate that V(H) gene usage in B-CLL may have prognostic impact
      independently of V(H) gene mutation status. The V1-69 gene is the most frequently
      rearranged V(H) gene in B-CLL and is almost always unmutated. We therefore
      investigated whether patients with a V1-69 gene rearrangement differ in clinical
      course and outcome with respect to patients expressing other unmutated V(H)
      genes. We show that V1-69 B-CLLs constitute a uniform group of patients that more
      often present at advanced clinical stages and require early treatment, but their
      survival does not differ significantly from patients with other unmutated V(H)
      genes.

PMID- 16797701
TI  - Vasoactive intestinal polypeptide and pituitary adenylate cyclase activating
      polypeptide: effects on insulin release in isolated mouse islets in relation to
      metabolic status and age.
AB  - Obesity and development of the metabolic syndrome is related to an increased
      parasympathetic tone and hyperinsulinemia. We have now studied the effects of age
      and metabolic status on glucose-induced insulin release stimulated by the
      neuropeptides vasoactive intestinal polypeptide (VIP; 10 nM) and pituitary
      adenylate cyclase activating polypeptide (PACAP; 10 nM), that are constituents of
      the parasympathetic nerves in the islets, and the cholinergic agonists
      acetylcholine (ACh; 10 microM) and carbachol (10 microM), in isolated islets from
      female obese ob/ob mice and lean mice. Both VIP and PACAP enhanced insulin
      secretion in islets from 4-week-old hyperglycemic ob/ob mice. VIP did not
      increase 11.1 mM glucose-induced insulin release in islets from 4-week-old lean
      normoglycemic mice and neither did PACAP in the absence of bicarbonate. The
      neuropeptides increased insulin release in islets from 9 to 10-month-old mice but
      VIP and PACAP had no effect in islets from very old mice. ACh had no effect in
      islets from 9 to 10-months and older ob/ob mice in the absence of bicarbonate.
      The combination of VIP and cholinergic agonists had an additive effect in islets
      from ob/ob mice, and PACAP combined with carbachol potentiated insulin release in
      islets from 4-week-old lean mice. VIP increased early phase insulin release in
      perifused islets from young mice. A higher concentration of theophylline was
      needed to potentiate glucose-induced insulin release in islets from young lean
      mice than in islets from old lean mice and ob/ob mice. The present results
      demonstrate age-related dynamics in the effects of neuropeptides affecting cAMP
      in pancreatic islets. We suggest that VIP and PACAP contribute to the developing
      metabolic syndrome in ob/ob mice by aggravating hyperinsulinemia.

PMID- 16797704
TI  - Effects of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, on human
      mast cells bearing wild-type or mutated codon 816 c-kit.
AB  - Most adults with systemic mastocytosis (SM) carry an activating mutation in the
      codon 816 of c-kit. We investigated the activity of the new tyrosine kinase
      inhibitor AMN107 on c-kit mutated mast cell lines and bone marrow samples from
      patients with SM and compared it to that of imatinib mesylate, a tyrosine kinase
      inhibitor effective in some patients with SM. In HMC-1(560) mast cells carrying
      wild-type codon 816 c-kit, AMN107 was very effective and as potent as imatinib in
      inhibiting cellular proliferation and inducing apoptosis (P<0.0823). By contrast,
      in HMC-1(560,816) cells bearing a c-kit mutation in codon 816, neither drug
      exerted a significant effect (P<0.0015). AMN107 was also as effective as imatinib
      in inhibiting phosphorylation of c-kit in HMC-1(560) cells. However, AMN107 had
      little effect on ex vivo survival of bone marrow mast cells with 816 c-kit
      mutation obtained from patients with SM. Based upon our results, AMN107 and
      imatinib are equipotent against mast cells with wild-type c-kit and those
      harboring the juxtamembrane D560G c-kit mutant but have no significant activity
      over the dose range tested against cells expressing the c-kit D816V mutant
      tyrosine kinase.

PMID- 16797705
TI  - Coding sequence and intron-exon junctions of the c-myb gene are intact in the
      chronic phase and blast crisis stages of chronic myeloid leukemia patients.
AB  - The c-myb gene encodes a transcription factor required for proliferation,
      differentiation and survival of normal and leukemic hematopoietic cells. c-Myb
      has a longer half-life in BCR/ABL-expressing than in normal cells, a feature
      which depends, in part, on PI-3K/Akt-dependent regulation of proteins interacting
      with the leucine zipper/negative regulatory region of c-Myb. Thus, we asked
      whether the stability of c-Myb in leukemic cells might be enhanced by mutations
      interfering with its degradation. We analyzed the c-myb gene in 133 chronic
      myeloid leukemia (CML) patients in chronic phase and/or blast crisis by
      denaturing-high performance liquid chromatography (D-HPLC) and sequence analysis
      of PCR products corresponding to the entire coding sequence and each exon-intron
      boundary. No mutations were found. We found four single nucleotide polymorphisms
      (SNPs) and identified an alternatively spliced transcript lacking exon 5, but
      SNPs frequency and expression of the alternatively spliced transcript were
      identical in normal and CML cells. Thus, the enhanced stability of c-Myb in CML
      blast crisis cells and perhaps in other types of leukemia is not caused by a
      genetic mechanism.

PMID- 16797706
TI  - Morphometric studies of cardiac myocytes of rats chronically treated with an
      organophosphate.
AB  - Organophosphate intoxication induces an acute cholinergic syndrome, but the long
      term effects of these compounds in the cardiocirculatory system are not known.
      The objective of the present work is to investigate if experimental chronic
      exposition to repetitive sublethal doses of organophosphate methamidophos can
      induce morphological changes in rat's hearts. Wistar albino adult male rats
      received a weekly enteral sublethal dose of the organophosphate methamidophos for
      12 consecutive weeks. After that we have performed histological and morphometric
      studies of their hearts. We have observed hypertrophy of cardiac myocites in
      treated animals, which was confirmed by morphometric studies (measure of smaller
      diameter of cardiac myocites). One of the possible explanations for the cardiac
      hypertrophy would be persistent systemic arterial hypertension in treated
      animals. However, another possible explanation would be direct sympathetic
      stimulation.

PMID- 16797707
TI  - Effects of waterborne Cd exposure on glutathione metabolism in Nile tilapia
      (Oreochromis niloticus) liver.
AB  - To explore the effects of cadmium (Cd) exposure of tilapia (Oreochromis
      niloticus) on hepatic glutathione (GSH) metabolism, tilapias were exposed to 3.0
      mg/L Cd for 1, 5, 10, 20, and 40 days. The contents of reduced GSH and oxidized
      GSH (GSSG) and the activities of enzymes involved in GSH metabolism and the GSSG
      GSH ratio were investigated. The results showed that reduced GSH were depleted
      progressively whereas the GSSG-GSH ratio increased. The activities of selenium
      dependent glutathione peroxidase, glutathione S-transferase and glucose-6
      phosphate dehydrogenase, and GSSG levels increased initially and decreased
      subsequently but still higher than the controls. Glutathione reductase activity
      dropped on the 40th day. A transient increase in gamma-glutamylcysteine syntheses
      activity was detected on the 20th day. The findings demonstrated that the hepatic
      GSH pool showed different reaction patterns associated with exposure period. The
      homeostatic mechanism was activated by short-term Cd exposure while the response
      ability weakened for a longer exposure.

PMID- 16797708
TI  - Personality disorders in rapists and murderers from a maximum security prison in
      Brazil.

PMID- 16797709
TI  - Optic disc topography and peripapillary retinal nerve fiber layer thickness in
      nonarteritic ischemic optic neuropathy and open-angle glaucoma.
AB  - OBJECTIVE: To evaluate the results of scanning laser tomography and scanning
      laser polarimetry (SLP) and the correlations with visual field damage (VFD) in
      eyes with nonarteritic ischemic optic neuropathy (n-AION) compared with eyes with
      open-angle glaucoma (OAG). DESIGN: Cross-sectional study. PARTICIPANTS: Thirty
      three eyes of 33 patients with n-AION and 33 eyes with OAG whose age and VFD
      evaluated with the Humphrey field analyzer were matched to those of the n-AION
      eyes. MAIN OUTCOME MEASURES: The parameters of optic disc topography obtained
      with the Heidelberg Retina Tomograph II (HRT II) and retinal nerve fiber layer
      (RNFL) thickness with GDx with variable corneal compensation and the correlation
      to VFD. RESULTS: The cup area, cup-to-disc area ratio, and mean cup depth were
      significantly smaller, and the cup shape measure more negative, in the n-AION
      eyes than in the OAG eyes (P<0.001), whereas rim area was significantly greater
      (P<0.001). Multivariate analyses showed that none of disc area, rim area, and
      mean cup depth in the n-AION eyes and only rim area (P = 0.029) in the OAG eyes
      was significantly associated with mean deviation (MD). Ellipse average of RNFL
      thickness significantly correlated with MD in the n-AION eyes (P = 0.045) and in
      the OAG eyes (P = 0.022). CONCLUSIONS: Disc topography of eyes with n-AION was
      quantitatively characterized by small and shallow cupping and a relatively large
      rim area compared to eyes with OAG matched for age and VFD. In eyes with n-AION,
      significant correlation with VFD was found only for the RNFL thickness evaluated
      with SLP but not for the HRT II parameters.

PMID- 16797710
TI  - Ocular infections caused by Providencia rettgeri.
AB  - PURPOSE: To report a series of patients with ocular infections caused by the
      rarely described gram-negative bacterium, Providencia rettgeri. DESIGN:
      Retrospective case series. PARTICIPANTS: Five patients with ocular infections who
      grew P. rettgeri after culture (2 keratitis, 1 dacryocystitis, 1 conjunctivitis,
      1 conjunctivitis/endophthalmitis). METHODS: Microbiology culture results positive
      for P. rettgeri were cross-referenced to identify the patients with ocular
      infections. Medical records of these patients were carefully reviewed. MAIN
      OUTCOME MEASURES: Descriptive analysis of each patient's history, potential risk
      factors, and clinical outcome. RESULTS: Five eyes in 2 institutions were found to
      be culture positive for the gram-negative bacterium P. rettgeri. The organism may
      cause keratitis, dacryocystitis, conjunctivitis, and endophthalmitis. Possible
      risk factors include a compromised ocular surface and coexisting medical
      morbidity, including urinary tract infections, recent hospitalizations, and an
      immunocompromised state. Culture and sensitivity profiles should guide treatment;
      resistant strains are being identified. CONCLUSIONS: Infections caused by P.
      rettgeri, although rare, are responsible for ocular morbidity. This report
      describes patient attributes, risk factors, and outcomes that will be helpful to
      ophthalmologists treating ocular infections. P. rettgeri should be acknowledged
      as a source of ocular infection.

PMID- 16797711
TI  - Magnetic resonance for evaluation of toxic encephalopathies: implications from
      animal experiments.
AB  - Examinations of brain of rats intoxicated with hexachlorophene or acrylamide with
      ultrahigh-field (4.7 T) proton magnetic resonance (MR) showed alterations
      consistent with clinical pictures in humans and morphological findings in
      experimental animals. On the other hand, conventional biochemical analyses have
      revealed that ethylene oxide, methyl bromide, and acrylamide inhibit creatine
      kinase (CK; an enzyme catalyzing the reaction: ATP+creatine<-
      >ADP+phosphocreatine) activities in the brain of animals. Thus, 31P MR combined
      with magnetization transfer may be utilized to monitor living humans (or animals)
      intoxicated with these chemicals by determining CK activities in the target
      organ.

PMID- 16797712
TI  - Pyruvate and oxaloacetate limit zinc-induced oxidative HT-22 neuronal cell
      injury.
AB  - During CNS ischaemia, accumulating evidence suggests that raised intracellular
      Zn(2+) levels may play a significant role in inducing neuronal cell death.
      Several mechanisms mediating Zn(2+)-induced cell death have been suggested,
      however the precise molecular mechanisms remain uncertain. Employing the HT-22
      murine hippocampal neuronal cell line, we have evaluated possible mechanisms of
      cytotoxic extracellular Zn(2+) insults. Increased extracellular Zn(2+) levels was
      found to induce concentration-dependent cytotoxicity. When tested at 200muM,
      Zn(2+) increased intracellular Zn(2+) levels (determined via FluoZin-3
      fluorescence) and rapidly induced cell death. However, neither L-type
      (nimodipine) nor T-type (mibefradil) voltage-activated Ca(2+) channel inhibitors
      limited Zn(2+)-induced cytotoxicity. Furthermore, and in contrast with
      staurosporine, Zn(2+) cytotoxic insults failed to induce significant caspase-3
      activation and were insensitive to the poly-caspase inhibitor, zVAD-fmk.
      Antioxidant co-application (Trolox and N,N'-diphenyl-1,4-phenylenediamine (DPPD))
      was neuroprotective versus 6h Zn(2+) insults. Additionally, despite inducing
      significant mitochondrial membrane potential loss, Zn(2+) failed to induce
      detectable increased superoxide production. However, both pyruvate and
      oxaloacetate were found to afford significant neuroprotection versus Zn(2+)
      cytotoxic insults, without significantly influencing intracellular Zn(2+)
      accumulation. We conclude that cultured HT-22 neurones are vulnerable to Zn(2+)
      cytotoxic insults via a non-caspase-3 mediated mechanism, which involves
      glycolytic inhibition.

PMID- 16797713
TI  - Translocation of PKC-betaII is mediated via RACK-1 in the neuronal cells
      following dioxin exposure.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to induce neurotoxic effects.
      However, the mechanism of TCDD-mediated signaling pathways and its possible
      molecular targets in neurons remains unknown. In this study, we analyzed effects
      of TCDD on neurofilament subunits, receptor for activated C kinase-1 (RACK-1),
      and PKC-betaII activity in developing neuronal cells. TCDD induced a significant
      increase of RACK-1, an adaptor protein for protein kinase C (PKC), in cerebellar
      granule cells in both dose- and time-dependent manner, indicating that RACK-1 is
      a sensitive molecular target in neuronal cells for TCDD exposure. TCDD induced a
      dose-dependent translocation of PKC-betaII from cytosol to membrane fractions.
      However, when RACK-1 induction was blocked by antisense oligonucleotide or alpha
      naphthoflavone, Ah receptor (AhR) inhibitor, the translocation of PKC-betaII was
      inhibited. Our data suggests that TCDD activates PKC-betaII via RACK-1 in an AhR
      dependent manner. This is the first report identifying RACK-1 as a target
      molecule involved in TCDD-mediated signaling pathways. TCDD exposure also
      increased the level of neurofilament-H mRNA. These results suggest that
      identification of target molecules may contribute to improve our understanding of
      TCDD-mediated signaling pathway and the risk assessment of TCDD-induced
      neurotoxicities.

PMID- 16797714
TI  - Studies of interaction between Rh(I) and human serum albumin in a "nanostructured
      biocatalyst" active in the hydroformylation reaction.
AB  - The interaction between Rh(CO)(2)(acac=acetylacetonate ion) and human serum
      albumin (HSA) in a hydrosoluble nanostructured biocatalyst active in homogeneous
      hydroformylation was characterised by means of matrix assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOFMS), high performance
      liquid chromatography mass spectrometry (HPLC-MS) and scanning electron
      microscopy (SEM). MALDI-TOFMS substantiates that the biocatalyst consists of a
      tetrameric structure of HSA that could bind up to 89 Rh(CO)(2)(+) units. A
      comparison between samples of pure HSA and the biocatalyst, both tryptic
      digested, showed a significant change in the tertiary structure of the protein in
      the HSA/Rh adduct, probably ascribable to the interaction of Rh(I) ions with
      sulphur atoms in the HSA moiety. SEM observations confirmed an evident
      denaturation of the protein and an outstanding correspondence between the surface
      distribution of Rh and S atoms; this is indirect evidence that the metal ion
      interacts strongly mainly with the sulphur atoms. Furthermore, an excellent
      agreement between calculated and measured (SEM) S/Rh elemental mean ratio was
      observed. Finally, an electrostatic interaction between Rh(I) and sulphur atoms
      was ruled out by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) findings.

PMID- 16797715
TI  - Formation of Cu(II)-brazilin complex in the presence of DNA and its activities as
      chemical nuclease.
AB  - Brazilin, a traditional medicine for the treatment of pain and inflammation,
      forms a complex with Cu(II) in the presence as well as the absence of DNA. The
      Cu(II)-brazilin complex exhibited the strand cleavage activity for the pBR322
      supercoiled DNA, converting supercoiled form to nicked form. The presence of
      various scavengers for the oxygen species suppresses or reduces the cleavage
      activity of the complex, indicating that the DNA cleavage is oxidative. The
      binding mode of the Cu(II)-brazilin complex was studied by absorption and CD
      spectroscopy. While a large metal-to-ligand charge transfer (MLCT) band was
      apparent when Cu(II) and brazilin was mixed in the presence and absence of DNA,
      the CD did not show any signal in the same region in the presence of DNA,
      suggesting a weak interaction between the Cu(II)-brazilin complex and DNA bases.

PMID- 16797716
TI  - New and future migraine therapy.
AB  - Modern neuroscience advanced our understanding of putative migraine mechanisms,
      which led to improved therapeutics. Indeed, mechanism-based acute migraine
      therapy gained steam in the early 1990s after the introduction of the triptans (5
      HT1B,D agonists). Post-triptans, novel targets such as calcitonin gene-related
      peptide (CGRP) antagonists, inhibitors of excitatory glutamatergic receptors, and
      nitric oxide synthase (NOS) inhibitors are leading the pack in this exploding
      field of discovery research. In contrast, novel therapeutic targets for migraine
      prevention are lacking despite a hugely unmet need. To date, migraine
      prophylactic drugs are advanced based on expanded indications for already
      approved pharmaceuticals (e.g., topiramate, valproate, propranolol, and timolol).
      An improved understanding of the predisposition to an attack, genomic
      discoveries, valid and reliable biomarkers and surrogates, and predictive
      preclinical models likely will unravel the neuronal substrates for central
      hyperexcitability and nociceptive dysmodulation, hopefully leading us to better
      mechanism-based targets for prevention, and ultimately yielding drugs with
      optimal therapeutic ratios or indices.

PMID- 16797717
TI  - Rapid isolation of synaptoneurosomes and postsynaptic densities from adult mouse
      hippocampus.
AB  - Previous postsynaptic density (PSD) isolation methodologies have utilized either
      whole brain or discrete brain regions of relatively large mammals such as dogs
      and rats. The present report details a simple and highly effective procedure for
      the rapid isolation of PSDs from small amounts of adult mouse hippocampus that
      has several advantages. First, by substituting synaptoneurosomes for synaptosomes
      as starting material, we have decreased the steps, time, and amount of tissue
      required to isolate PSDs. Second, by modifying critical steps in the synaptic
      isolation protocols we were able to isolate PSDs from less than 200 mg of mouse
      hippocampi in 3 h. Electron micrographs of isolated synaptoneurosomes showed
      presynaptic vesicles and densely stained membranes representing PSDs.
      Morphological examination of these PSDs by electron microscopy revealed a
      preparation that seems to be quite pure, with little or no membrane
      contamination. A comparison by Western blot analysis of synaptoneurosome and PSD
      fractions suggests that this technique yields a purified sample. Moreover, two
      different protocols using swing and fixed bucket rotors were used for this small
      scale PSD isolation and both resulted in a very pure partition, supporting the
      idea that this procedure is reliable and consistent.

PMID- 16797720
TI  - The child bipolar questionnaire: a dimensional approach to screening for
      pediatric bipolar disorder.
AB  - BACKGROUND: The Child Bipolar Questionnaire (CBQ) is a rapid screener with a Core
      Index subscale of symptom dimensions frequently reported in childhood-onset
      bipolar disorder (BD) and scoring algorithms for DSM-IV BD, with and without
      attention-deficit/hyperactivity disorder (ADHD), and the proposed Narrow, Broad,
      and Core phenotypes. This report provides preliminary data on the reliability and
      validity of the CBQ. METHOD: Test-retest and inter-rater reliability of the CBQ
      were assessed. The ability of CBQ screening diagnoses and of the CBQ Core Index
      subscale to effectively predict diagnostic classification by structured interview
      was assessed using the K-SADS P/L. RESULTS: Preliminary test-retest data showed
      excellent reliability for both the CBQ total score (r = 0.82) and the Core Index
      subscale (r = 0.86). Preliminary validity data was also promising. CBQ screening
      algorithms performed with a specificity of 97% and a sensitivity of 76% in
      classifying subjects with K-SADS P/L diagnosis of BD vs. no BD. The Core Index
      subscale had excellent agreement with K-SADS P/L diagnosis (k = 0.84) in
      classifying BD, ADHD-only, and no diagnosis and demonstrated 100% sensitivity and
      86% specificity in classifying BD vs. no BD. LIMITATIONS: This preliminary data
      is from a sample enriched with bipolar disorder cases. Further validation is
      needed with samples in which childhood-onset BD is rarer and diagnoses more
      diverse. CONCLUSIONS: The CBQ shows potential for rapid and economically feasible
      identification of possible childhood-onset BD cases as defined by DSM-IV criteria
      as well as by alternate disease phenotypes. Further validation studies will focus
      on inpatient and outpatient samples with a broader range of variability.

PMID- 16797718
TI  - A multiplexed proteomics approach to differentiate neurite outgrowth patterns.
AB  - We report here a method for proteomics pattern discovery by utilizing a self
      organizing map approach to analyze data obtained from a novel multiplex iTRAQ
      proteomics method. Through the application of this technique, we were able to
      delineate the early molecular events preceding dorsal root ganglia neurite
      outgrowth induced by either nerve growth factor (NGF) or an immunophilin ligand,
      JNJ460. Following pattern analysis we discovered that each neurotrophic agent
      promoted mostly distinct increases in protein expression with few overlapping
      patterns. In the NGF-treated group, proteins possessing "biosynthesis function"
      (p < 0.002) and "ribosome localization" (p < 0.0003) were increased, while
      proteins promoting "organogenesis" (p < 0.004) and related "signal transduction"
      (p < 0.008) functions were notably increased in the JNJ460-treated group. This
      study suggests that the properties of neurite outgrowth triggered by NGF and
      JNJ460 can be distinguished at the proteome level. Multiplexed proteomics
      analysis, along with pattern discovery bioinformatics tools, has the capability
      to differentiate subtle neuroproteomics patterns.

PMID- 16797719
TI  - An investigation of the problem of two-layered immunohistochemical staining in
      paraformaldehyde fixed sections.
AB  - In sections of paraformaldehyde fixed brain tissue, stained using
      immunohistochemical methods, the distribution of staining within the sections is
      not uniform. Whilst stained cells are seen at the top and bottom surfaces, the
      central thicknesses of the sections contain little or no immunoreactivity. This
      presents a major problem for quantification, as each section contains a
      population of cells that is not visualized by the staining method. Following
      extensive investigation of this phenomenon, we report that the failure of full
      thickness, immunohistochemical staining is not a failure of the
      immunohistochemical methodology per se, nor is it related directly to the
      thickness of the sections used. Rather, the problem lies in the chemistry of the
      tissue itself, and originates during fixation of the tissues using
      paraformaldehyde-based perfusion methods, which render the cell membranes
      impermeable to one or more components of the staining protocol. We show that this
      impermeability is affected by addition of membrane-disrupting agents to the
      fixative, and by a reduction of exposure to paraformaldehyde during fixation. The
      present investigation contributes to the development of new fixation protocols,
      optimised for use in both immunohistochemical methods and morphometric analyses.

PMID- 16797721
TI  - Treatment of anxiety disorders in the Finnish general population.
AB  - BACKGROUND: Treatments for anxiety disorders in the general population are not
      widely investigated. We determined the proportion, type and determinants of
      treatment in the Finnish general population. METHODS: Within the Health 2000
      Study, a representative sample (n = 6005) of adults (age > 30 years) were
      interviewed in 2000-2001 with the Composite International Diagnostic Interview (M
      CIDI) to assess the presence of DSM-IV mental disorders during the preceding 12
      months. Logistic regression models were used to examine factors influencing the
      type of treatment (pharmacotherapy and/or psychological treatment) and also the
      types of pharmacotherapy (antidepressants, anxiolytics, or sedatives and
      hypnotics) used for anxiety disorders. RESULTS: For individuals with an anxiety
      disorder, 40% (95/229) currently used psychotropic medication, 23% (55/229) used
      antidepressants, 19% (44/229) anxiolytics and 17% (41/229) sedatives or
      hypnotics. Of those using health care services for mental health reasons (34%,
      76/229), 80% (61/76) received pharmacotherapy. Only 45% (34/76) reported having
      psychological treatment, with few having more than 4 visits (27%, 20/76). Living
      in a semi-urban environment, retirement and high perceived disability increased
      the likelihood of pharmacotherapy-only treatment; higher education and
      comorbidity with mood disorders increased the likelihood of psychological
      treatment. General practitioners more often than psychiatrists provided
      pharmacotherapy treatment alone (67% vs. 34%, p < 0.05), particularly anxiolytics
      or sedatives. LIMITATIONS: Use of mental health services and psychological
      treatment were based on self-reports. No data on duration of pharmacotherapy was
      available. CONCLUSIONS: Anxiety disorders remain largely untreated in the general
      population. Among those seeking treatment, pharmacotherapy predominates, whereas
      even brief psychotherapies are rare. Contrary to clinical guidelines, anxiolytics
      and sedatives are commonly used instead of antidepressants.

PMID- 16797722
TI  - Preterm delivery induced by LPS in syngeneically impregnated BALB/c and NOD/SCID
      mice.
AB  - Strategies of lipopolysaccharide (LPS) stimulation with or without previous toll
      like receptor 4 (TLR4) blocking were pursued to investigate the mechanism of LPS
      induced preterm delivery in syngeneically impregnated BALB/c and non-obese
      diabetic (NOD)/LtSz-scid/scid (NOD/SCID [severe combined immunodeficiency] for
      short) mice. The LPS-stimulated mice were killed at the beginning of preterm
      labor and pooled placentas were collected in each mouse. Cell surface expression
      of TLR4, CD80, and intracellular TNF-alpha in placenta CD45(+) cell population
      was determined by flow cytometry. It displayed that preterm delivery could be
      induced by LPS in BALB/c, while the NOD/SCID seemed to be resistant to LPS
      induction. TLR4 expression was not changed in either BALB/c or NOD/SCID mice upon
      LPS-stimulation, but the CD45(+)CD80(+) cell percentage was elevated in both
      groups. The CD45(+)TNF-alpha(+) cell percentage was increased merely in BALB/c
      after the stimulation, while no such trend was observed in NOD/SCID mice. In
      BALB/c, the effect of LPS on CD80 and TNF-alpha expression could be abrogated by
      previous TLR4 blocking, subsequently prevent LPS-induced preterm delivery. In
      another design, NK cell blocking was performed at earlier stage of gestation by
      injections of anti-asialo GM1 antiserum (ASGM1). It appeared that LPS-induced
      preterm delivery could be partially prevented by this blocking in BALB/c mice.
      Such data, together with the diversity of sensitivity to LPS induction observed
      in BALB/c and NOD/SCID mice, imply that LPS interacts with TLR4, triggers the
      mobilization of CD45(+)CD80(+) cells, results in elevated production of
      inflammatory cytokines, and finally results in preterm delivery. In addition, NK
      cells may be involved in the signaling cascade, and the lack of functional NK
      cells in the NOD/SCID may be why these mice appeared to be less sensitive to LPS
      induced premature labor.

PMID- 16797723
TI  - Immunopathogenic pathways in canine inflammatory myopathies resemble human
      myositis.
AB  - Progress in the treatment of inflammatory myopathies is impeded by the lack of
      suitable animal models. Inflammatory myopathies occur spontaneously in the dog,
      are a heterogeneous group of disorders, and are more common than in humans.
      Clinical signs of weakness and muscle atrophy are reliably present, and there are
      histological and immunohistological similarities to forms of human myositis. In
      this study, microarray technology followed by quantitative real-time PCR and
      immunohistochemistry on muscle biopsy sections was used to investigate gene
      expression in cases of canine inflammatory myopathies. Several genes involved
      with innate and adaptive immunity were highly upregulated including those that
      participate in macrophage and dendritic cell activation and migration, and
      antigen processing and presentation. Other genes including those that participate
      in B cell growth, development, migration and activation, immunoglobulin genes,
      genes in pro-inflammatory and anti-inflammatory pathways, and genes involved with
      tissue remodeling were upregulated. In previous reports utilizing microarray
      technology in human myositis, there was activation of similar pathways involved
      in the immune response. This study strengthens the argument that forms of canine
      myositis may be important animal models of human myositis and suggests useful
      biomarkers for therapeutic response using the dog in pre-clinical trials.

PMID- 16797724
TI  - Equine insect bite hypersensitivity: immunoblot analysis of IgE and IgG subclass
      responses to Culicoides nubeculosus salivary gland extract.
AB  - Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by
      IgE-mediated reactions to bites of Culicoides and sometimes Simulium spp. The
      allergens causing IBH are probably salivary gland proteins from these insects,
      but they have not yet been identified. The aim of our study was to identify the
      number and molecular weight of salivary gland extract (SGE) proteins derived from
      Culicoides nubeculosus which are able to bind IgE antibodies (ab) from the sera
      of IBH-affected horses. Additionally, we sought to investigate the IgG subclass
      (IgGa, IgGb and IgGT) reactivity to these proteins. Individual IgE and IgG
      subclass responses to proteins of C. nubeculosus SGE were evaluated by immunoblot
      in 42 IBH-affected and 26 healthy horses belonging to different groups (Icelandic
      horses born in Iceland, Icelandic horses and horses from different breeds born in
      mainland Europe). Additionally, the specific antibody response was studied before
      exposure to bites of Culicoides spp. and over a period of 3 years in a cohort of
      10 Icelandic horses born in Iceland and imported to Switzerland. Ten IgE-binding
      protein bands with approximate molecular weights of 75, 66, 52, 48, 47, 32,
      22/21, 19, 15, 13/12 kDa were found in the SGE. Five of these bands bound IgE
      from 50% or more of the horse sera. Thirty-nine of the 42 IBH-affected horses but
      only 2 of the 26 healthy horses showed IgE-binding to the SGE (p<0.000001).
      Similarly, more IBH-affected than healthy horses had IgGa ab binding to the
      Culicoides SGE (19/22 and 9/22, respectively, p<0.01). Sera of IBH-affected
      horses contained IgE, IgGa and IgGT but not IgGb ab against significantly more
      protein bands than the sera of the healthy horses. The cohort of 10 Icelandic
      horses confirmed these results and showed that Culicoides SGE specific IgE
      correlates with onset of IBH. IBH-affected horses that were born in Iceland had
      IgGa and IgGT ab (p< or =0.01) as well as IgE ab (p=0.06) against a significantly
      higher number of SGE proteins than IBH-affected horses born in mainland Europe.
      The present study shows that Culicoides SGE contains at least 10 potential
      allergens for IBH and that IBH-affected horses show a large variety of IgE
      binding patterns in immunoblots. These findings are important for the future
      development of a specific immunotherapy with recombinant salivary gland
      allergens.

PMID- 16797725
TI  - Extensive analysis of different allelelic structures of the chicken BF2 and
      beta2m proteins.
AB  - No information is available to date on the different allelelic structures of the
      chicken MHC class I (BF2) and beta2m proteins. To elucidate the structure, new
      allelic beta2m and five different BF2 genes were expressed solubly and purified
      in a pMAL-p2X/E. coli TB1 system. The 2D structure was detected by circular
      dichroism (CD) spectroscopy, and the 3D structures of their peptide-binding
      domain (PBD) were analyzed by homology modeling. The sequence lengths of the
      alpha-helix, beta-sheet, turn, and random coil in the five BF2 proteins were 69
      73 aa, 67-72 aa, 35-37 aa, and 94-98 aa, respectively. The new beta2m protein
      displayed a typical beta-sheet. Homology modeling of the different BF2 and beta2m
      proteins demonstrated similarities to the structure of human and rat MHC class I
      proteins. The 3D structure, however, revealed that the BF2 and beta2m structures
      were unique. The correct refolding of recombinant BF2 and beta2m proteins might
      be a powerful tool to further detect antigenic peptides.

PMID- 16797726
TI  - Molecular aspects of human FcgammaR interactions with IgG: functional and
      therapeutic consequences.
AB  - The binding of IgG antibodies to receptors for the Fc region of IgG (FcgammaR) is
      a critical step for the initiation and/or the control of effector immune
      functions once immune complexes have been formed. Site-directed and random
      mutagenesis as well as domain-swapping, NMR and X-ray cristallography have made
      it possible to get detailed insights in the molecular mechanisms that govern
      IgG/FcgammaR interactions and to define some of the structural determinants that
      impact IgG binding to the various FcgammaR. It has demonstrated the role of
      particular stretches and individual residues located in the lower hinge region of
      the CH2 domain and in the CH2 and CH3 domains of the Fc region. The importance of
      the sugar components linked to asparagine 297 in the binding properties of IgG1,
      the human IgG isotype the most widely used in antibody-based therapies, has been
      also highlighted. These data have led to the engineering of a new generation of
      monoclonal antibodies for therapeutic use with optimized effector functions.

PMID- 16797727
TI  - Bimodal effect of nitric oxide in the enzymatic activity of indoleamine 2,3
      dioxygenase in human monocytic cells.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an enzyme that depletes l-tryptophan, which
      provokes a decreased T cell response. This enzyme is expressed in human placenta,
      and can be also induced in many cell types such as monocytes, where endothelial
      (eNOS) and inducible (iNOS) nitric oxide synthases are also expressed. Previous
      studies have shown that nitric oxide (NO) inhibits IDO activity, which could
      cause a suppression of the biological function of IDO when both enzymes are
      coexpressed. As NO can exert different effects depending on several factors such
      as its concentration, we studied the effect of low concentrations of NO in the
      IDO activity in the U-937 and THP-1 monocytic cell lines. Results demonstrated
      that NO caused a bimodal effect in IDO function in IFN-gamma-stimulated monocytic
      cells: while high micromolar concentrations of the NO donors SIN-1 and DETA-NO
      decreased IDO activity, low micromolar concentrations of these NO donors
      increased IDO activity. Related to this, the NOS inhibitors L-NMMA and
      aminoguanidine, and the calmodulin antagonist W7 also decreased IDO activity. The
      effect of NO in IDO activity was not through cGMP production. Immunoprecipitation
      analysis showed a nitration of the IDO protein in unstimulated and stimulated U
      937 and THP-1 cells. However, in monocyte-derived macrophages, with a higher NO
      production, aminoguanidine increased IDO activity, but the NOS substrate arginine
      decreased IDO activity. Considering the role of IDO in suppression, these results
      suggest a function in tolerance of the NOS enzymes depending on the NO
      production.

PMID- 16797728
TI  - Effects of IFN-beta, leptin and simvastatin on LIF secretion by T lymphocytes of
      MS patients and healthy controls.
AB  - In multiple sclerosis (MS), oligodendrocyte injury is believed to be caused by an
      aberrant immune response initiated by autoreactive T cells. Increasing evidence
      indicates that inflammatory responses in the central nervous system are not
      exclusively detrimental, but may also exert protective effects. Such protective
      effects are potentially mediated by the local secretion of neurotrophic factors
      by immune cells. We previously reported that T cells and monocytes in vitro and
      in inflammatory MS lesions produce leukaemia inhibitory factor (LIF), a member of
      the neuropoietic family of neurotrophins. In the present study, we report a
      reduced LIF production by CD4+ T cells of relapsing remitting MS patients as
      compared to healthy controls. Furthermore, immunomodulatory agents such as
      leptin, IFN-beta and simvastatin were studied for their potential to alter LIF
      and secretion of other cytokines by T cells and monocytes of relapsing remitting
      MS patients and healthy controls. Low doses of simvastatin, but not IFN-beta or
      leptin enhanced LIF secretion by CD4+ T cells of RR-MS patients. We further
      demonstrated that LIF did not influence viability, proliferation and cytokine
      secretion of T cells. Together these data provide new information on the
      regulation of LIF secretion by immune cells. Further insights into the complex
      regulation of neurotrophic factors such as LIF may prove useful for treatment of
      MS.

PMID- 16797729
TI  - Quality of life after surgical treatment of children with obstructive sleep
      apnea: long-term results.
AB  - OBJECTIVES: To measure the long-term impact of tonsillectomy and/or adenoidectomy
      (T&A) on children with obstructive sleep apnea (OSA). METHODS: A controlled study
      on 101 OSA children, operated between June 1999 and January 2001. The OSD-6 was
      used to assess the results. The caregivers of these patients were asked about
      their subjective impression prior to surgery (first evaluation), 8 days after the
      procedure (second evaluation), and with a minimum follow-up of 3 years after the
      operation (third evaluation). RESULTS: Mean of follow-up was 61.9+/-13.1 months
      (range, 36-75 months). The total mean survey score showed a highly significant
      improvement when comparing first evaluation versus second evaluation, first
      evaluation versus third evaluation, and second evaluation versus third evaluation
      (p<0.001). In the same way, we found a favourable outcome in the six domains when
      visits were compared. Only sleep disturbance between second and third evaluation
      did not show a significant improvement (p>0.05). There were not differences in
      the postsurgical outcome of quality of life (QOL) according to the remaining
      factors studied (p>0.05). CONCLUSIONS: Children with OSA who undergo surgery show
      a significant long-term improvement in QOL.

PMID- 16797730
TI  - A novel stent for the treatment of persistent buccopharyngeal membrane.
AB  - We describe a new stent design for treatment of persistent buccopharyngeal
      membrane. The patient is a male child diagnosed at birth with persistent
      buccopharyngeal membrane, managed in our institution from birth to present age of
      2.5 years. We describe to problems and challenges in management for this rare
      anomaly by means of a custom made polyurethane stent.

PMID- 16797731
TI  - Finnish adenoidectomy and tympanostomy rates in children; national variation.
AB  - OBJECTIVES: To assess upper respiratory surgery rates in Finnish children and
      compare the rates of adenoidectomy and tympanostomy tubes in 2002 with the 1987
      cohort. METHODS: Descriptive study of national upper respiratory surgery in
      Finland in 1987 and 2002; adenoidectomies, tympanostomy tubes and combination of
      these two. Surgical rates were viewed in the light of child density and number of
      primary care physicians and otorhinolaryngologists. RESULTS: Rates of
      adenoidectomy and tympanostomy tubes were highest in Western Finland and lowest
      in Eastern Finland (p<0.00001). Peak-age for adenoidectomy and tympanostomy tubes
      was in the second year of life. Surgery was most common in boys (p<0.00001). Both
      the numbers of otorhinolaryngologists and operations increased from 1987 to 2002;
      the largest surgery increase, 7.3%, was found in Western Finland. CONCLUSION:
      Large national differences in rates of paediatric adenoidectomy and tympanostomy
      tubes in Finland propose that national guidelines have not had an impact on the
      selection of children for surgery.

PMID- 16797732
TI  - Detection of virulent Newcastle disease virus using a phage-capturing dot blot
      assay.
AB  - Newcastle disease virus (NDV) strains can be classified as virulent or avirulent
      based upon the severity of the disease. Differentiation of the virus into
      virulent and avirulent is necessary for effective control of the disease.
      Biopanning experiments were performed using a disulfide constrained phage
      displayed heptapeptide library against three pathotypes of NDV strains: velogenic
      (highly virulent), mesogenic (moderately virulent) and lentogenic (avirulent). A
      phage clone bearing the peptide sequence SWGEYDM capable of distinguishing
      virulent from avirulent NDV strains was isolated. This phage clone was employed
      as a diagnostic reagent in a dot blot assay and it successfully detected only
      virulent NDV strains.

PMID- 16797733
TI  - Surface display of an internal His-tag on virus-like particles of Nudaurelia
      capensis omega virus (NomegaV) produced in a baculovirus expression system.
AB  - Nudaurelia capensis omega virus (NomegaV) is a member of the Tetraviridae, a
      family of small, icosahedral, non-enveloped, (+) sense single-stranded RNA insect
      viruses with T = 4 symmetry. NomegaV virus-like particles (VLPs), which are
      morphologically indistinguishable from native virions and capable of packaging
      heterologous RNA, may be produced in the baculovirus expression system. As a
      first step towards manipulating the tropism of tetraviral nanoparticles
      (Capsivectors), a (His)6-tag was inserted into the GH loop (between Ala 378 and
      Gly 379) of the surface-exposed Ig-like domain of NomegaV capsid protein (p70).
      His-tagged p70 produced in a baculovirus expression system self-assembled into
      omegaHis VLPs that exhibited similar morphological and RNA encapsidation
      properties as wild-type NomegaV VLPs produced in the same system. Two assays
      using paramagnetic pre-charged nickel beads confirmed that multiple affinity tags
      were present on the surface of omegaHis VLPs and were capable of binding. These
      results indicate that the GH loop is a suitable site for the retargeting of
      NomegaV particles for potential biotechnological applications.

PMID- 16797734
TI  - Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex
      virus types 1 and 2 and varicella-zoster virus.
AB  - Acyclovir and vidarabine both exhibit anti-herpetic activity. Because different
      mechanisms of action of vidarabine and acyclovir have been reported, we analyzed
      their combined anti-herpetic activity on plaque formation of herpes simplex virus
      (HSV)-1, HSV-2, and varicella-zoster virus (VZV) by isobolograms. The results
      indicate that acyclovir and vidarabine have a synergistic effect on wild type HSV
      1, HSV-2, and VZV. The susceptibility of thymidine kinase-deficient HSV-1 to
      vidarabine was not affected by the presence of acyclovir, suggesting that
      phosphorylation of acyclovir is essential for synergism. The combined anti-HSV
      activity of acyclovir and vidarabine against phosphonoacetic acid-resistant HSV-1
      with DNA polymerase mutation did not show synergism in contrast to that against
      wild-type herpesviruses. Alteration of the substrate specificity of viral DNA
      polymerase to acyclovir and vidarabine annihilated the synergism. Thus, the
      nature of their binding sites on DNA polymerase is important to the synergistic
      anti-herpesvirus activity of acyclovir and vidarabine.

PMID- 16797735
TI  - L-nucleoside enantiomers as antivirals drugs: a mini-review.
AB  - The discovery that some nucleoside analogues endowed with the unnatural L
      configuration can possess biological activities has been a significant
      breakthrough in antiviral chemotherapy. In this regard, lamivudine (3TC) was the
      first L-nucleoside enantiomer approved against HIV and HBV, and several other L
      nucleosides are currently under clinical development as antiviral agents.

PMID- 16797736
TI  - Brain and behavioural evidence for rest-activity cycles in Octopus vulgaris.
AB  - Octopus vulgaris maintained under a 12/12h light/dark cycle exhibit a pronounced
      nocturnal activity pattern. Animals deprived of rest during the light period show
      a marked 'rebound' in activity in the following 24h. 'Active' octopuses attack
      faster than 'quiet' animals and brain activity recorded electrically intensifies
      during 'quiet' behaviour. Thus, in Octopus as in vertebrates, brain areas
      involved in memory or 'higher' processes exhibit 'off-line' activity during rest
      periods.

PMID- 16797737
TI  - Cerebral glucose transporters expression and spatial learning in the K-ATP
      Kir6.2(-/-) knockout mice.
AB  - K-ATP channels formed of the Sur and Kir subunits are widely distributed in the
      brain. Sur1-Kir6.2 is the most common combination of K-ATP channel subunits in
      the brain and Kir6.2 plays an important role in glucose metabolism through
      pancreatic insulin secretion or hypothalamic glucose sensing. K-ATP channels have
      also been reported to play a role in memory processing. Therefore, the aim of the
      present experiment is to assess the gene and protein expression of GLUT1, GLUT3
      and GLUT4 in various brain regions of Kir6.2(-/-) K-ATP knockout mice and to test
      their working memory performance. GLUT4 was measured using two antibodies, one
      recognizing an intracellular epitope and the other, an extracellular epitope.
      Relative to their corresponding wild type, semi-quantitative immunohistochemistry
      showed that GLUT4 protein expression as measured by a GLUT4 antibody recognizing
      an extracellular epitope was increased in the Kir6.2(-/-) K-ATP mice. However,
      there was only a small increase in GLUT4 labeling using the GLUT4 antibody
      recognizing the intracellular epitope. These results suggest a compensatory
      higher GLUT4 inclusion at the cellular neuronal membrane in the cerebral cortex,
      hippocampus and cerebellum of the Kir6.2(-/-) K-ATP knockout mice. However, there
      was no change in GLUT4 gene expression assessed by TaqMan PCR except for a
      decrease in the cerebellum of these mice. Working memory performance of the
      Kir6.2(-/-) K-ATP mice was disrupted at age of 12 weeks but not at 5 weeks. The
      mild glucose intolerance that is observed in the Kir6.2 knockout mice is unlikely
      to have created the memory deficits observed. Rather, in light of the effects of
      K-ATP channel modulators on memory, the memory deficits in the Kir6.2(-/-) K-ATP
      mice are more likely due to the absence of the Kir6.2 and possible disruption of
      the GLUT4 activity in the brain.

PMID- 16797738
TI  - Deficits in acquisition of spatial learning after dorsomedial telencephalon
      lesions in goldfish.
AB  - Acquisition of spatial learning is an important function of mammalian
      hippocampus. In order to identify the brain areas in teleost fish that are
      homologous to mammalian hippocampus, the present study examined the effects of
      lesions in the dorsal area of the caudal telencephalon of goldfish (Carassius
      auratus) on the acquisition of spatial learning. An open-field maze that was
      similar to the dry version of the Morris water maze was used. The task consisted
      of habituation and postoperative training to reach the position of the bait.
      Extramaze cues were visible in the habituation sessions in experiment 1, while
      they were blocked and not visible in the habituation sessions in experiment 2.
      Only in experiment 2, there was a significant deficit in the performance in the
      training sessions in the goldfish with damage to the dorsomedial area of the
      caudal telencephalon (DM). These data showed that blocking of the extramaze cues
      in the habituation sessions caused deficits in postoperative acquisition of
      spatial learning in the training sessions in the goldfish with DM lesions. Latent
      learning in the habituation sessions, however, eliminated the effects of the DM
      lesions on spatial learning. The present study suggests that the DM plays a
      critical role in acquisition of spatial learning.

PMID- 16797739
TI  - Targeting steroid receptor coactivator-1 expression with locked nucleic acids
      antisense reveals different thresholds for the hormonal regulation of male sexual
      behavior in relation to aromatase activity and protein expression.
AB  - Steroid receptors such as the androgen and estrogen receptors require the
      presence of several proteins, known as coactivators, to enhance the transcription
      of target genes. The first goal of the present study was to define the role of
      SRC-1 on the steroid-dependent expression of the aromatase protein and its
      activity in male Japanese quail. The second goal was to analyze the rapid
      plasticity of the POM following antisense treatment interruption. We confirm here
      that the inhibition of SRC-1 expression by daily intracerebroventricular
      injections of locked nucleic acid antisense oligonucleotides in the third
      ventricle at the level of the preoptic area-hypothalamus (HPOA) significantly
      reduces testosterone-dependent male sexual behavior. In the first experiment,
      aromatase protein expression in HPOA was inhibited in SRC-1-depleted males but
      the enzymatic activity remained at the level measured in controls. We observed in
      the second experiment a recovery of the behavioral response to testosterone
      treatment after interruption of the antisense injection. However, several
      morphological characteristics of the POM were not different between the control
      group, the antisense-treated birds and antisense-treated birds in which treatment
      had been discontinued 3 days earlier. Antisense was also less effective in
      knocking-down SRC-1 in the present experiments as compared to our previous study.
      An analysis of this variation in the degree of knock-down of SRC-1 expression
      suggests dissociation among different aspects of steroid action on brain and
      behavior presumably resulting from the differential sensitivity of behavioral and
      neurochemical responses to the activation by testosterone and/or its estrogenic
      metabolites.

PMID- 16797740
TI  - Octopus arm choice is strongly influenced by eye use.
AB  - This study aims to investigate the octopus' eye and arm coordination and raises
      the question if visual guidance determines choice of arm use. Octopuses possess
      eight seemingly identical arms but have recently been reported to show a
      preference as to which arm they use to initiate contact with objects. These
      animals also exhibit lateralized eye use, therefore, a connection between eye and
      arm preference seems possible. Seven Octopus vulgaris were observed during
      approach, contact initiation and exploration of plastic objects that were
      positioned on three different levels in the water column. The subjects most
      commonly used an arm to initiate contact with an object that was in a direct line
      between the eye used to look at the object, and the object itself. This indicates
      that choice of arm use is spatially rather opportunistic when depending on visual
      guidance. Additionally, first contact with an object was usually established by
      the central third of the arm and in arm contact sequences neighboring arms were
      the most likely to follow an arm already touching the object. Although results
      point towards strong eye/arm coordination, we did not find lateralized behavior
      in this experiment. Results are discussed from a neuro-anatomical, behavioral and
      ecological perspective.

PMID- 16797742
TI  - Characterization of human cytoglobin gene promoter region.
AB  - Cytoglobin (CYGB) is a member of the vertebrate globin family together with
      hemoglobin, myoglobin and neuroglobin. Although the physiological function of
      CYGB is still unclear, spectroscopic studies show that CYGB contains a
      hexacoordinated heme pocket similar to other pentacoordinated globin proteins.
      CYGB shares a common phylogenetic ancestry with vertebrate myoglobin from which
      it diverged by duplication before the appearance of jawed vertebrates. The
      objective of this study is to identify the regulatory and promoter region of the
      human cytoglobin gene. 5' unidirectional deletion constructs demonstrated that
      the proximal promoter elements of human CYGB gene are located between -1113 to 
      10 relative to the translation start site. Site-directed mutagenesis showed that
      mutation of a c-Ets-1 motif at -1008 and Sp1 motifs at -400, -230 and -210
      remarkably decreased the promoter activity. Gel shift assays confirmed the
      binding of DNA-nuclear proteins to these motifs. All these results indicate that
      CYGB gene expression can be up-regulated by c-Ets-1 and Sp1 motifs.

PMID- 16797741
TI  - Red blood cell defects and malaria.
AB  - Malaria is a major cause of childhood death throughout much of the tropical
      world. As a result, it has exerted a powerful force for the evolutionary
      selection of genes that confer a survival advantage. Identifying which genes are
      involved, and how they affect malaria risk, is a potentially useful way of
      exploring the host-parasite relationship. To date, some of the best-described
      malaria-protective polymorphisms relate to genes that affect the structure or
      function of red blood cells (RBC). Recent years have seen significant advances in
      our understanding of the importance of some of these genes, including glycophorin
      C (GYPC); complement receptor 1 (CR1); band 3 (SLC4A1); pyruvate kinase (Pklr);
      and the genes for alpha-(HBA) and beta-globin (HBB). The challenge for the future
      must be to convert these advances into fresh approaches to the prevention and
      treatment of malaria.

PMID- 16797743
TI  - Partial characterization of the mouse alpha-sarcoglycan promoter and its
      responsiveness to MyoD.
AB  - The mouse alpha-sarcoglycan gene is expressed in muscle cells during
      differentiation, but its transcriptional regulation is not understood. We have
      characterized the promoter region of the mouse alpha-sarcoglycan gene. This
      region is composed of positive and negative regulatory elements that respond to
      the myogenic differentiation environment. Accordingly, MyoD transactivates the
      alpha-sarcoglycan full-length and the proximal promoter. Chromatin
      immunoprecipitation assays revealed that MyoD, TFIID, and TFIIB interact with the
      distal promoter in C2C12 myoblasts, a stage at which the alpha-SG promoter
      appears to drive basal activity. In myotubes, such factors are located
      concomitantly at the distal promoter and at a DNA region around the proximal
      promoter. In agreement with these results, TFIID and TFIIB co-immunoprecipitate
      with MyoD. We conclude that the alpha-SG promoter is activated by MyoD, which
      interacts with TFIID and TFIIB in a protein complex differentially located at the
      distal promoter and around the proximal promoter during myogenic cell
      differentiation.

PMID- 16797744
TI  - Long-term (11-year) statin therapy following percutaneous coronary intervention
      improves clinical outcome and is not associated with increased malignancy.
AB  - BACKGROUND: Statins have been proven to reduce cardiac events and mortality.
      However, there are few studies dealing with the long-term efficacy of statin
      therapy following percutaneous coronary intervention (PCI). METHODS: We collected
      data from 575 consecutive patients who underwent PCI between 1987 and 1992. The
      baseline data, mortality and incidence of cardiovascular events of patients given
      statins and those not given statins at the time of PCI were compared. RESULTS:
      There were 243 patients in the statin group and 332 patients in the non-statin
      group. During follow-up (11.0+/-3.0 years), 68 patients died. At about 10 years,
      statin use was significantly associated with lower all-cause mortality (8.2%
      versus 14.5%, P=0.023) and cardiac death (2.5% versus 6.9%, P=0.017). After
      adjusting for variables, statin use was found to be an independent predictor of
      death from all causes (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.29
      0.99, P=0.048) and cardiac death (HR 0.24, 95% CI 0.07-0.80, P=0.02). CONCLUSION:
      Statin use at the time of PCI was associated with a significantly reduced risk of
      death from all causes and cardiac death. Furthermore, this study provides
      evidence of a clinical benefit at about 10 years of statin use in patients who
      underwent PCI.

PMID- 16797745
TI  - Associations of apolipoprotein B with pulse pressure and glucose in Chinese
      families with familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL), with a marked elevation of
      apolipoprotein B (apoB), is estimated to cause 10-20% of premature coronary
      artery disease. However, little data are available to demonstrate the
      associations of apoB with pulse pressure and glucose levels in FCHL families in
      China. This study was to investigate the potential influence factors for blood
      pressure and glucose phenotypes in FCHL families by multiple linear regression
      analysis. We recruited 147 FCHL relatives and 90 spouses, aged 30 to 60 years,
      from 42 Chinese families with FCHL. Our results showed that triglyceride and low
      density lipoprotein cholesterol were associated with fasting glucose levels (all
      P<0.05). Body mass index and glucose significantly correlated to systolic blood
      pressure, diastolic blood pressure, and mean arterial pressure, respectively (all
      P<0.05). Furthermore, apoB was significantly related to pulse pressure and
      glucose in FCHL families (all P<0.05). Thus, this study demonstrates that apoB is
      significantly associated with pulse pressure and glucose levels in FCHL families.
      Accordingly, our data suggest that apoB may be a candidate risk marker for pulse
      pressure and glucose in FCHL populations.

PMID- 16797746
TI  - Depression in patients with acute myocardial infarction: influence on autonomic
      nervous system and prognostic role. Results of a five-year follow-up study.
AB  - BACKGROUND: Although previous studies demonstrated an association between
      depressive symptoms and cardiac mortality after acute myocardial infarction (AMI)
      little is known about the possible mechanisms of this association. The aim of
      this study was to determine whether depressed patients present a cardiac
      autonomic dysfunction and whether this could represent the mediator of the
      influence of depression on their prognosis. METHODS: One hundred consecutive
      patients with AMI were recruited between January and December 1999. Major
      Depressive Disorder (MDD) was diagnosed by structured clinical interview and the
      presence of symptoms of depression was evaluated with self-administered Beck
      Depression Inventory (BDI). The influence of depression on autonomic nervous
      system was investigated measuring heart rate variability (HRV) and heart rate
      (HR) during 24-hour electrocardiographic monitoring. The end-points of the study
      were all-cause mortality, recurrent-AMI, revascularization and a composite end
      point of all the previous. Potential confounders for depression status and events
      were entered into a multivariate regression model. RESULTS: Fifteen patients met
      the criteria for MDD and 35 patients showed mild-to-moderate symptoms of
      depression; women had a higher prevalence of depression than men (35% vs 9%;
      p<0.01). Depression was not related to the severity of ischaemic disease or to
      other clinical and demographic variables. Patients with MDD showed lower HRV
      (76+/-25 SD vs 99+/-33 SD ms; p<0.01) and higher HR (77+/-12 SD vs 68+/-9 SD bpm;
      p<0.01) than patients without MDD; moreover mild to moderate symptoms of
      depression (BDI score > or = 10) were associated with lower HRV (84+/-25 SD vs
      102+/-35 SD ms; p=0.01) but not with significantly higher HR. After a mean follow
      up of 60 months MDD was associated with an increase of all-cause mortality (OR
      12; 95% CI 2.6-56; p<0.01) and of composite end-point (OR 2; 95% CI 1.2-3.6;
      p=0.01) but not with re-AMI and revascularization. In a simple regression model
      HRV values were predictors of mortality (p<0.01). However when added in the
      multiple regression model HRV did not have an independent correlation with the
      end-points considered and did not modify the correlation between depression and
      mortality. CONCLUSIONS: Patients with post-AMI depression have a cardiac
      autonomic dysfunction as reflected by decreased HRV and increased HR. This
      autonomic dysfunction seems not to be an independent mediator of the increased
      mortality observed in depressed patients during a 5-year follow-up.

PMID- 16797747
TI  - Evaluation of pulmonary vascular response to inhaled iloprost in heart transplant
      candidates with pulmonary venous hypertension.
AB  - OBJECTIVE: Chronic left-heart failure is often associated with the development of
      pulmonary venous hypertension. In heart transplant candidates this is of great
      significance because the healthy donor heart has to compensate the increased
      right-ventricular afterload. Right-ventricular dysfunction is still responsible
      for 19% of all early deaths after orthotopic heart transplantation. Careful
      preoperative assessment of pulmonary vascular resistance by right-heart
      catheterization is essential. Reversibility testing is generally carried out to
      clarify therapeutic options for the post-transplant period. The objective of this
      case series is to report our institutional experience with inhaled iloprost
      compared to the common used oxygen/nitroglycerin method for reversibility
      testing. METHODS: Right-heart catheterization was performed in 23 patients with
      severely impaired left-ventricular function (EF < or = 25%, pVO2 < or = 14
      ml/kg/min, NYHA III or IV) with combined pulmonary venous hypertension (TPG > 12
      mm Hg and or PVR > 250 dyn x s x cm(-5)). An intraindividual comparison was
      performed between of the hemodynamic effect with oxygen/nitroglycerin s.l. and
      inhaled iloprost. RESULTS: The transpulmonary gradient fell significantly from an
      initial 16 mm Hg to 13 mm Hg on oxygen/nitroglycerin s.l. compared to 10 mm Hg on
      inhaled iloprost. Pulmonary vascular resistance fell significantly from an
      initial 344 dyn x s x cm(-5) to 270 dyn x s x cm(-5) on oxygen/nitroglycerin s.l.
      compared to 209 dyn x s x cm(-5) on inhaled iloprost. On inhaled iloprost a
      moderate systemic effect was noticed. CONCLUSION: In heart transplant candidates
      with pulmonary venous hypertension reversibility testing with inhalation of
      iloprost is a save method and significantly more effective than the combination
      of inhaled oxygen plus nitroglycerin s.l.

PMID- 16797748
TI  - Coronary flow, VO2 peak and anaerobic threshold in patients with dilated
      cardiomyopathy.
AB  - BACKGROUND: Coronary flow is influenced by several determinants and may change
      according to external stimuli. In patients with dilated cardiomyopathy (DC),
      adaptive mechanisms could induce alterations in coronary flow, possibly related
      to oxygen consumption. METHODS: In 67 consecutive patients with DC (mean age
      52.06+/-13.84, 52 male gender, left ventricle ejection fraction (LVEF) 29.49%+/
      8.68) and normal coronary angiography findings, coronary flow in left anterior
      descending (LAD), right coronary artery (RC) and left circumflex (LCx) was
      reported as TIMI frame count (TFC). All patients underwent a cardiopulmonary test
      with VO2 peak and anaerobic threshold (AT) measurement, New York Heart
      Association (NYHA) class stratification, two-dimensional echocardiographic
      evaluation including LVEF and left ventricle end-diastolic diameter (LVEDD)
      assessment. All patients were receiving optimal medical treatment. RESULTS: In a
      multivariate analysis, a statistically significant correlation was found between
      VO2 peak and TFC (B 7.61, p<0.001, R2 0.61 for LAD; B 3.42, p<0.001, R2 0.33 for
      RC); an inverse correlation was found between AT and TFC (B -9.77, p<0.001, R2
      0.61 for LAD; B -4.26, p<0.001, R2 0.33 for RC). CONCLUSIONS: Coronary flow is
      related to VO2 peak and AT in patients with DC, suggesting a "compensatory"
      mechanism.

PMID- 16797749
TI  - Constrictive pericarditis: an unusual clinical entity suggested during dobutamine
      stress echocardiography.
AB  - A 44-year-old female presents with disabling dyspnea and is unable to perform a
      regular treadmill stress test; instead a dobutamine stress echocardiogram is
      performed and although negative for ischemia reveals a vigorous paradoxical
      motion of the interventricular septum with dilatation of the inferior vena cava
      without respiratory variation and an increased diastolic flow signal in the
      hepatic veins after expiration with the infusion of dobutamine. The diagnosis of
      constrictive physiology is confirmed with cardiac magnetic resonance imaging
      (MRI) and right heart hemodynamics and the patient underwent pericardiectomy
      without complications with resolution of symptoms.

PMID- 16797750
TI  - Eplerenone suppresses neointima after coronary stenting in pigs: could it be
      extrapolated to stent restenosis in humans?

PMID- 16797751
TI  - Polymorphism of p53 gene codon 72 in Kuwaiti with coronary artery disease and
      diabetes.
AB  - BACKGROUND AND AIM: Polymorphism in the p53 gene at codon 72 has been linked to
      the development of certain diseases including cancer. A possible association
      between such polymorphism and the development of coronary artery disease (CAD)
      and diabetes is being investigated, but no conclusive evidence has been reached
      yet. Our study is the first pilot study to be conducted on Kuwaitis suffering
      from CAD and diabetes, aiming at investigating the possible existence of the
      above association. MATERIALS AND METHODS: We analyzed the genotype distribution
      and allele frequency of p53 gene at codon 72 in 158 CAD samples and 110 controls,
      and in 142 diabetic and 130 controls. RESULTS: Analysis of CAD patients revealed
      an alarming significant association between the disease and the existence of
      diabetes (P=0.0007). Also, the CAD patients had significantly higher level of
      triglyceride (P<0.0001) and cholesterol (P<0.0001) as compared to control. As for
      the polymorphism in p53 gene codon 72, we could not detect any association with
      the genotype Pro/Pro, Pro/Arg or Arg/Arg distribution (P=0.28) or allele (Pro or
      Arg) frequency (P=0.25) in the CAD patients. Similarly, no association was found
      with the genotype Pro/Pro, Pro/Arg or Arg/Arg distribution (P=0.44) or allele
      (Pro or Arg) frequency (P=0.26) in the diabetic patients. CONCLUSION: CAD seems
      to be strongly linked to diabetes in Kuwait. Polymorphism in the p53 gene at
      codon 72 revealed no significant association with the development of CAD or
      diabetes in Kuwait, which confirms other similar results obtained in the US and
      Asia.

PMID- 16797752
TI  - Ventral cardiac denervation increased right coronary arterial blood flow.
AB  - BACKGROUND: Cardiac denervation accompanied with coronary artery bypass surgery
      has been widely performed for the treatment of vasospastic angina associated with
      atherosclerotic coronary artery disease. However, the effect of cardiac
      denervation on phasic coronary blood flow patterns of the left anterior
      descending coronary artery (LAD), left circumflex coronary artery (LCX) and right
      coronary artery (RCA) remains unknown. This study aimed to investigate the effect
      of cardiac denervation on phasic coronary blood flow patterns of the LAD, LCX and
      RCA. METHODS: Phasic coronary blood flow patterns were analyzed using three flow
      probes placed around the LAD, LCX and RCA with and without LAD stenosis. Ventral
      cardiac denervation (VCD) was performed in 8 pigs, and 16 pigs were used as
      control subjects. Autonomic activities before and after the VCD were quantified
      by wavelet analysis of heart rate variability. RESULTS: The mean LAD flow (34.4+/
      9.4 to 32.6+/-7.1 ml/min, p=0.638) and mean LCX flow (26.3+/-10.2 to 27.2+/-6.0
      ml/min, p=0.825) showed no significant change after VCD, while the mean RCA flow
      (31.3+/-9.0 to 38.2+/-11.2 ml/min, p=0.003) significantly increased. The
      hemodynamic variables in the VCD group were well maintained after creation of LAD
      stenosis, while they deteriorated in the control group. The low-frequency
      components, high-frequency components and their ratio did not change after VCD.
      CONCLUSIONS: VCD prevented the deterioration of cardiac function after creation
      of an LAD stenosis and resulted in an increase of the mean RCA flow. VCD did not
      affect autonomic nervous system activity.

PMID- 16797753
TI  - Application of a semi-dependent latent model in the Bayesian estimation of the
      sensitivity and specificity of two faecal culture methods for diagnosis of
      paratuberculosis in sub-clinically infected Greek dairy sheep and goats.
AB  - In this study, we compared the frequency of isolation of Mycobacterium avium
      subsp. paratuberculosis (MAP) from faecal samples grown on Herrold's egg-yolk
      medium (HEYM) or on Lowenstein-Jensen (LJ) medium and estimated the sensitivity
      (Se) and specificity (Sp) of the methods separately in sub-clinically infected
      Greek dairy sheep and goats, using latent-class models and Bayesian estimation
      procedures. Faecal and blood samples were collected from 400 animals > or =1 year
      old in April-May 2002. The HEYM supported growth of MAP better than the LJ method
      and their agreement was very poor (weighted kappa=0.062 (95% CI: -0.098, 0.222)).
      There was no evidence of dependence between the Ses whereas the Sps were
      positively correlated. Thus, a semi-dependent model that assumed independence of
      Ses and accounted for the dependence of Sps was adopted. Under this model, the
      parallel interpretation of the results of the two methods gave median estimates
      and 95% credible intervals (CrIs) for Se(par), Sp(par) of 15% (CrIs: 3, 45%), 96%
      (92, 98%) in sheep and 16% (6, 36%) and 97% (94, 99%) in goats.

PMID- 16797754
TI  - An anaphylactoid reaction from amifostine.

PMID- 16797755
TI  - Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma:
      concepts and guidelines.
AB  - BACKGROUND AND PURPOSE: To describe new concepts for radiation fields in patients
      with early stage Hodgkin lymphoma treated with a combined modality. PATIENTS AND
      MATERIALS: Patients receiving combined modality therapy with at least 2 or 3
      cycles of chemotherapy prior to radiotherapy. Pre- and postchemotherapy cervical
      and thoracic CT scans are mandatory and should be performed, whenever possible,
      in the treatment position with the use of image fusion capabilities. A pre
      chemotherapy PET scan is strongly recommended to increase the detection of
      involved lymph nodes. RESULTS: Radiation fields are designed to irradiate the
      initially involved lymph nodes exclusively and to encompass their initial volume.
      In some cases, radiation fields are slightly modified to avoid unnecessary
      irradiation of muscles or organs at risk. CONCLUSIONS: The concept of involved
      node radiotherapy (INRT) described here is the first attempt to reduce the size
      of radiation fields compared to the classic involved fields used in adult
      patients. Proper implementation of INRT requires adequate training and an
      efficient prospective or early retrospective quality assurance program.

PMID- 16797756
TI  - Correlating digit span performance and event-related potentials to assess working
      memory.
AB  - Event-related brain potentials (ERPs) were recorded during a computerized and
      modified version of the Digit Span Backwards (DB) task from the Wechsler Adult
      Intelligence Scale-Third Edition (WAIS-III). The modified DB version (ERP-DB
      task) was divided into two sections of 2, 4, 6 and 8 digits in length (Group 1)
      and 3, 5 and 7 digits in length (Group 2). Each trial had a study phase and a
      test phase. For the study phase, a series of digits was presented sequentially
      and aurally to 20 participants (10 for each group). For the test phase, a second
      series of digits was also presented sequentially and aurally that either
      corresponded to the reverse order of the digits in the study phase (correct
      condition) or had one digit in the sequence replaced by an incorrect digit
      (incorrect condition). The traditional DB task of the WAIS-III was also
      administered for comparison purposes. A prolonged positive slow wave (PSW)
      peaking between 450 and 750 ms was elicited to incorrect condition trials. For
      each participant, a derived measure was calculated from the ERP differentiation
      between correct and incorrect conditions. The derived measure was defined as the
      mean of the t-values obtained from the correct and incorrect waveform comparison,
      within the temporal interval that encompassed this component. The strongest
      statistical correlations between the derived measure and the traditional DB test
      scores were found at the Pz site (Group 1: r=0.79; Group 2: r=0.59). This
      statistical approach shows that it is possible to adequately relate an
      individual's performance on a traditional measure of working memory and ERP
      patterns. Overall, we believe that this kind of ERP approach holds promise as a
      technique for assessing quantitatively non-communicative patients.

PMID- 16797757
TI  - Brain regions concerned with perceptual skills in tennis: an fMRI study.
AB  - Sporting performance makes special demands on perceptual skills, but the neural
      mechanisms underlying such performance are little understood. We address this
      issue, making use of fMRI to identify the brain areas activated in viewing and
      responding to video sequences of tennis players, filmed from the opponent's
      perspective. In a block-design, fMRI study, 9 novice tennis players watched video
      clips of tennis play. The main stimulus conditions were (1) serve sequences, (2)
      non-serve behaviour (ball bouncing) and (3) static control sequences. A button
      response was required indicating the direction of serve (left or right for serve
      sequences, middle button for non-serve and static sequences). By comparing
      responses to the three stimulus conditions, it was possible to identify two
      groups of brain regions responsive to different components of the task. Areas
      MT/MST and STS in the posterior part of the temporal lobe responded either to
      serve and to non-serve stimuli, relative to static controls. Serve sequences
      produced additional regions of activation in the parietal lobe (bilateral IPL,
      right SPL) and in the right frontal cortex (IFGd, IFGv), and these areas were not
      activated by non-serve sequences. These regions of the parietal and frontal
      cortex have been implicated in a "mirror neuron" network in the human brain. It
      is concluded that the task of judgement of serve direction produces two different
      patterns of response: activations in the MT/MST and STS concerned with primarily
      with the analysis of motion and body actions, and activations in the parietal and
      frontal cortex associated specifically with the task of identification of
      direction of serve.

PMID- 16797758
TI  - On females' lateral and males' bilateral activation during language production: a
      fMRI study.
AB  - This study focuses on sex/gender and language in fMRI research. We explore the
      question of similarities and differences in 22 men and 22 women, respectively, in
      a fMRI language production task of fluent narration in which covert language
      production was contrasted with an auditory attentional task. In women, a left
      lateralised activation concentrated in BA 44 while in men activation was more
      frontal in BA 45 and more often bilateral. This result is the opposite of those
      shown so far. Interestingly, the effect is only significant at the level of group
      analysis; it disappears when analysing activation at the level of the individual
      subject. We argue that sex/gender differences in the brain should be regarded
      much more critically, due to the numerous variables interacting and thus
      confounding with sex/gender. Our present study, too, cannot resolve the
      controversy about the existence of sex/gender similarities and differences in
      fMRI-language investigations.

PMID- 16797759
TI  - Human astrocytes express 14-3-3 sigma in response to oxidative and DNA-damaging
      stresses.
AB  - The 14-3-3 protein family consists of seven isoforms, most of which are expressed
      abundantly in neurons and glial cells, although the sigma isoform, a p53 target
      gene originally identified as an epithelium-specific marker, has not been
      identified in the human central nervous system. Here, we show that human
      astrocytes in culture expressed 14-3-3sigma under stress conditions. By Western
      blot, the expression of 14-3-3sigma, p53 and p21 was coordinately upregulated in
      astrocytes following exposure to hydrogen peroxide, 4-hydroxy-2-nonenal (4-HNE)
      or etoposide, a topoisomerase II inhibitor. 14-3-3sigma was induced by treatment
      with 5-aza-2'-deoxycytidine, suggesting a hypermethylated status of the gene
      promoter in astrocytes. In vivo, a small subset of hypertrophic reactive
      astrocytes, often showing a multinucleated morphology, expressed 14-3-3sigma in
      active demyelinating lesions of multiple sclerosis (MS) and ischemic lesions of
      cerebral infarction, where the expression of 4-HNE and 8-hydroxy-2'
      deoxyguanosine was enhanced in reactive astrocytes. Microarray analysis of
      etoposide-treated astrocytes verified upregulation of p53-responsive genes and
      concurrent downregulation of mitotic checkpoint-regulatory genes. These
      observations suggest that 14-3-3sigma might serve as a marker of oxidative and
      DNA-damaging stresses inducing the mitotic checkpoint dysfunction in reactive
      astrocytes under pathological conditions.

PMID- 16797760
TI  - Antimicrobial effect of spices and herbs on Vibrio parahaemolyticus.
AB  - The antimicrobial effects of spices and herbs from 18 plant species were examined
      on a foodborne pathogen, Vibrio parahaemolyticus, with the use of combinations of
      temperatures and nutrient levels. Basil, clove, garlic, horseradish, marjoram,
      oregano, rosemary, and thyme exhibited antibacterial activities at incubation of
      30 degrees C, while with the exception of horseradish, the same spices and
      additional 7 species exhibited the activities at 5 degrees C. The lowest MIC
      (minimum inhibitory concentration) was 0.125% observed in clove and marjoram at
      30 degrees C in a nutrient rich medium. Lowering of incubation temperature
      produced little effect on the MICs except for turmeric. The decreasing of the MIC
      in turmeric appeared to be basically attributed to the sensitivity of the
      bacterium to coldness. In nutrient poor medium, the lowest was 0.001 and 0.00025%
      in marjoram at 30 degrees C and at 5 degrees C, respectively. The sensitivity to
      several spices and herbs was similar among different clinical serotypes including
      the emerging strain O3:K6. These results suggest that the spices and herbs can be
      practical for protecting seafood from the risk of contamination by V.
      parahaemolyticus and used in hurdle technology with low temperature.

PMID- 16797761
TI  - Simultaneous detection by PCR of Escherichia coli, Listeria monocytogenes and
      Salmonella typhimurium in artificially inoculated wheat grain.
AB  - A multiplex PCR procedure was established to detect Escherichia coli, Listeria
      monocytogenes and Salmonella typhimurium in artificially inoculated wheat grain.
      The PCR protocol with an enrichment step successfully detected all three
      organisms inoculated together in non-autoclaved wheat grain. After a one day
      enrichment, E. coli, L. monocytogenes and S. typhimurium were detected at levels
      of 56, 1800 and <54 CFU/mL, respectively, in the initial sample. For L.
      monocytogenes, an improved detection limit of <62 CFU/mL was achieved using
      singleplex PCR. For autoclaved wheat grain inoculated with the three bacterial
      strains individually, a detection limit of 3 CFU/mL was achieved after an
      enrichment step. The ability to test for the three bacteria simultaneously will
      save time and increase the ability to assure grain quality.

PMID- 16797762
TI  - Influence of food system conditions on N-acyl-L-homoserine lactones production by
      Aeromonas spp.
AB  - Eleven of 13 Aeromonas strains were shown to produce AHLs. Results of TLC showed
      that N-butanoyl-L-homoserine lactone (C4-HSL) was the main AHL produced in LB
      medium at 30 degrees C. The influence of different carbon sources, temperature,
      pH values and salt concentrations on AHL production was determined in eight A.
      hydrophila and one A. caviae strain. Additionally a quantitative study of C4-HSL
      production by A. hydrophila strain 519 under different conditions was performed.
      Positive results were found in the AHL induction assay for some Aeromonas strains
      in cultures in LB agar incubated at 12 degrees C after 72-96 h. The induction of
      the sensor strains by Aeromonas spp. occurred in LB medium supplemented with all
      carbon sources in a concentration of 0.5%. The production of C4-HSL by A.
      hydrophila 519 was found until 3.5% (w/v) of NaCl. For pHs close to the
      neutrality the C4-HSL production by A. hydrophila was evident after 24-48 h of
      incubation. A. hydrophila 519 produced C4-HSL under anaerobic conditions. Also,
      the AHL production by Aeromonas strains was studied in simulate agar of shrimp,
      fish and some vegetables. The production of AHLs was evident by almost all the
      test strains in shrimp simulated agar. In fish agar only for one of three fish
      species tested, positive results were found. Induction assay in vegetables
      simulated agar showed principally negative results, probably because of the
      presence of inhibitory compounds in these vegetables.

PMID- 16797763
TI  - Disruption of hexokinase II (HXK2) partly relieves glucose repression to enhance
      production of human kringle fragment in gratuitous recombinant Saccharomyces
      cerevisiae.
AB  - The GAL1 gene encoding galactokinase was disrupted in a recombinant Saccharomyces
      cerevisiae strain in which production of LK8 protein, a kringle fragment of human
      apolipoprotein, is under the control of GAL1 promoter. Null mutation of the HXK2
      gene was introduced further in the gal1Delta strain to relieve glucose
      repression. A pattern for LK8 expression was compared for the two recombinant S.
      cerevisiae systems in continuous and fed-batch cultivations. A critical dilution
      rate in continuous cultivation that repressed LK8 expression was significantly
      higher for the gal1Deltahxk2Delta strain than that for the gal1Delta strain to
      sustain the LK8 production even at high glucose consumption rate. Expressed LK8
      for the gal1Delta strain was not detectable when the dilution rate exceeded 0.05
      h(-1). Maximum LK8 concentration of 57 mgl(-1) was obtained in glucose-limited
      fed-batch cultivation of the gal1Deltahxk2Delta strain, corresponding to a 13.8
      fold enhancement compared with the gal1Delta strain grown under the same
      conditions.

PMID- 16797764
TI  - A new method to characterize chemically and topographically nanopatterned
      surfaces.
AB  - Surface chemistry of topographically patterned grooved samples with ridges of 150
      nm width, adsorbed with self-assembled monolayers (SAMs) of alkanethiols on gold,
      have been characterized by near edge X-ray absorption fine structure (NEXAFS)
      spectroscopy. Analysis reveals that NEXAFS may discriminate between different
      chemistries adsorbed to the tops, sidewalls and grooves of the patterns.

PMID- 16797765
TI  - Antibiosis by Bacillus amyloliquefaciens ribonuclease barnase expressed in
      Escherichia coli against symbiotic and endophytic nitrogen-fixing bacteria.
AB  - A modified antibiosis assay was used to evaluate growth inhibition of symbiotic
      and endophytic bacteria by E. coli strains producing Bacillus amyloliquefaciens
      ribonuclease, barnase. Inhibition zones were only observed when the assays were
      performed in minimal medium agar. However, bacterial growth inhibition was not
      detected when using rich medium or susceptible strains expressing the
      ribonuclease inhibitor protein, barstar. Our results suggest that barnase may act
      as a broad range bacteriocin. The ecological significance of these results is
      discussed.

PMID- 16797766
TI  - Modeling and simulation of Streptomyces peucetius var. caesius N47 cultivation
      and epsilon-rhodomycinone production with kinetic equations and neural networks.
AB  - This study focuses on comparing different kinetic growth models and the use of
      neural networks in the batch cultivation of Streptomyces peucetius var. caesius
      producing epsilon-rhodomycinone. Contois, Monod and Teissier microbial growth
      models were used as well as the logistic growth modeling approach, which was
      found best in the simulations of growth and glucose consumption in the batch
      growth phase. The lag phase was included in the kinetic model with a CO2 trigger
      and a delay factor. Substrate consumption and product formation were included as
      Luedeking-Piret and logistic type equations, respectively. Biomass formation was
      modeled successfully with a 6-8-2 network, and the network was capable of biomass
      prediction with an R2-value of 0.983. Epsilon-rhodomycinone production was
      successfully modeled with a recursive 8-3-1 network capable of epsilon
      rhodomycinone prediction with an R2-value of 0.903. The predictive power of the
      neural networks was superior to the kinetic models, which could not be used in
      predictive modeling of arbitrary batch cultivations.

PMID- 16797767
TI  - Simple procedures for the construction of a robust and cost-effective cell-free
      protein synthesis system.
AB  - In this study, as a part of our efforts to improve the robustness and economical
      feasibility of cell-free protein synthesis, we developed a simple method of
      preparing the cell extracts used for catalyzing cell-free protein synthesis
      reactions. We found that the high-speed centrifugation, pre-incubation, and
      dialysis steps of the conventional procedures could be omitted without losing the
      translational activity of the resulting cell extract. Instead, a simple
      centrifugation step at low speed (12,000 RCF for 10 min) followed by a brief
      period of incubation was sufficient for the preparation of an active extract to
      support cell-free protein synthesis with higher productivity and consistency.
      Compared to the present standard procedures for the preparation of the S30
      extract, the overall cost of the reagents and processing time were reduced by 80
      and 60%, respectively.

PMID- 16797768
TI  - Cloning, purification and biochemical characterization of a thrombus-ditargeting
      thrombolytic agent, comprised of annexin B1, ScuPA-32K and fibrin-adherent
      peptide.
AB  - The development of thrombolytic agent could provide invaluable progress for
      antithrombotic therapy. In this paper, we reported the cloning, purification and
      biochemical characterization of AnxB1ScuPAFap, a thrombus-ditargeting chimera
      composed of annexin B1, low molecular single-chain urokinase (ScuPA-32K) and
      fibrin-adherent peptide (dodecapeptide, Fap). In vitro test showed that, the
      chimera was a thrombolytic agent with anticoagulant activity and thrombus
      ditargeting with the activated-platelet membrane binding and fibrin clot binding
      activity. Compared to urokinase, the chimera had less reperfusion time, higher
      reperfusion ratio, and less bleeding effects on coronary thrombolysis by clot
      lysis assay in dogs. Thus, the chimera appeared to be suitable for thrombolytic
      therapy of thrombus diseases.

PMID- 16797769
TI  - HCV NS2 protein inhibits cell proliferation and induces cell cycle arrest in the
      S-phase in mammalian cells through down-regulation of cyclin A expression.
AB  - Chronic hepatitis C virus (HCV) infection often leads to liver cancer. NS2
      protein is a HCV hydrophobic transmembrane protein that associates with several
      cellular proteins in mammalian cells. In this report, we investigated the
      functions of NS2 protein by examining its effects on cell growth and cell cycle
      progression. Stable NS2-expressing HeLa and Vero cell lines were established by
      transfection of the cells with pcDNA3.1(-)-NS2 followed by selection of the
      transfected cells in the presence of G418. We found that the proliferation rates
      of both NS2-expressing cell lines were inhibited by 40-50% compared with the
      control cells that were transfected with pcDNA3.1(-) control vector. Cell cycle
      analysis of these NS2-expressing cell lines shows that the proportion of cells in
      the S-phase increased significantly compared to that of control cells that do not
      express NS2 protein, suggesting NS2 protein induces cell cycle arrest in the S
      phase. Further studies showed that the induction of cell cycle arrest in the S
      phase by NS2 protein is associated with the decrease of cyclin A level. In
      contrast, the expression of NS2 protein does not affect the levels of cyclin
      dependent kinase CDK2, CDK4, cyclin D1, or cyclin E. Our results suggest that HCV
      NS2 protein inhibits cell growth and induces the cell cycle arrest in the S-phase
      through down-regulation of cyclin A expression, which may be beneficial to HCV
      viral replication. Our findings not only provide information in the understanding
      mechanism of HCV infection, but also provide guidance for the future development
      of potential therapeutics for the prevention and treatment of the viral
      infection.

PMID- 16797770
TI  - Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after
      spinal cord injury.
AB  - Neurotrophins have been shown to promote axonal growth and regeneration after
      spinal cord injury. The therapeutic utility of neurotrophins may be enhanced by
      using a controlled delivery system to increase the duration of neurotrophin
      availability following injury. Such a delivery system can be incorporated into a
      bioactive scaffold to serve as a physical bridge for regeneration. This study
      assessed the effect of controlled delivery of neurotrophin-3 (NT-3) from fibrin
      scaffolds implanted in spinal cord lesions immediately following 2-mm ablation
      injury in adult rats. Nine days after injury, fibrin scaffolds containing the
      delivery system and NT-3 (1000 ng/mL) elicited more robust neuronal fiber growth
      into the lesion than did control scaffolds or saline (1.5- to 3-fold increase).
      Implantation of fibrin scaffolds resulted in a dramatic reduction of glial scar
      formation at the white matter border of the lesion. Hindlimb motor function of
      treated animals did not improve relative to controls at 12 weeks post-injury.
      Thus, controlled delivery of NT-3 from fibrin scaffolds enhanced the initial
      regenerative response by increasing neuronal fiber sprouting and cell migration
      into the lesion, while functional motor recovery was not observed in this model.

PMID- 16797771
TI  - T cell infiltration and prognosis in HCC patients.

PMID- 16797772
TI  - ER stress: can the liver cope?
AB  - Hepatocytes contain abundant endoplasmic reticulum (ER) which is essential for
      protein metabolism and stress signaling. Hepatic viral infections, metabolic
      disorders, mutations of genes encoding ER-resident proteins, and abuse of alcohol
      or drugs can induce ER stress. Liver cells cope with ER stress by an adaptive
      protective response termed unfolded protein response (UPR), which includes
      enhancing protein folding and degradation in the ER and down-regulating overall
      protein synthesis. When the UPR adaptation to ER stress is insufficient, the ER
      stress response unleashes pathological consequences including hepatic fat
      accumulation, inflammation and cell death which can lead to liver disease or
      worsen underlying causes of liver injury, such as viral or diabetes-obesity
      related liver disease.

PMID- 16797773
TI  - Intrahepatic gene expression in human alcoholic hepatitis.
AB  - BACKGROUND/AIMS: Alcoholic hepatitis remains an important cause of morbidity and
      mortality. Treatment remains unsatisfactory, in part, due to limited
      understanding of the pathogenesis. The aim of this study is to define the global
      intrahepatic expression profile of human alcoholic hepatitis. METHODS: Gene
      expression was analysed by DNA microarray on RNA isolated from liver of patients
      with alcoholic hepatitis (AH, n = 8), alcoholic steatosis (AS, n = 9) and
      explants from non-diseased donor liver controls (ND, n = 7). Differential
      expression of selected genes was confirmed by real-time RT-PCR and
      immunohistochemistry. RESULTS: Cluster analysis allowed differentiation of
      alcoholic hepatitis from alcoholic steatosis. The gene expression profile of AH
      revealed 586 genes differentially expressed from AS and 211 genes differentially
      expressed from that of ND liver. In comparison, only 98 genes were differentially
      expressed in AS from ND. Novel differentially expressed genes in AH in comparison
      to ND and AS included claudins, osteopontin, CD209, selenoprotein and genes
      related to bile duct proliferation. Real-time RT-PCR confirmed up-regulation of
      IL-8, osteopontin, and TNFRSF14 and down-regulation of SAMeS and CD209.
      CONCLUSIONS: This study has defined the intrahepatic gene expression profile of
      human alcoholic hepatitis and revealed a number of novel differentially expressed
      genes.

PMID- 16797774
TI  - Motivation of chemical industry social responsibility through Responsible Care.
AB  - Advocates of corporate social responsibility argue corporations should not only
      meet the needs of shareholders, but other key stakeholders including the
      community, customers, suppliers, and employees. Since 1988, the chemical industry
      has engaged in a major self-regulatory "Responsible Care" industry-wide social
      responsibility campaign to ensure environmental, public health, safety, and
      security performance among member companies. Contrary to the arguments of
      advocates of corporate social responsibility that such efforts meet the needs of
      stakeholders other than shareholders such as the community, the primary goal of
      the Responsible Care effort has been to change public concerns and opinion about
      chemical industry environmental and public health practices while also opposing
      support for stronger and more expensive public health and environmental
      legislation and regulation of chemical products, even if warranted.

PMID- 16797775
TI  - Estimation of an index of regional health needs in Spain using count regression
      models with filter.
AB  - The aim of this study is to obtain a measure of health needs at regional level,
      on the basis of information provided by the health module of the Survey of
      Disabilities, Deficiencies and State of Health, 1999 (SDDSH99). The methodology
      includes a careful selection of the independent variables and both estimations as
      tests of alternative regression models. The results show that, in the five
      analysed use dimensions, important differences exist in the clinical practice for
      a same health necessity (horizontal inequity) in function of the residence area.
      Nevertheless, the main results and conclusions indicate that, as the framework of
      analysis is broadened, adding different healthcare services, and as the
      population size of the region is increased, the relative healthcare needs
      converge to the percentage of population of each region.

PMID- 16797776
TI  - Quality of life in the Palestinian context: an inquiry in war-like conditions.
AB  - This study aims to elucidate the concept of quality of life (QOL) in a unique
      environment characterized by protracted and ongoing conflict, beginning with the
      utilization of the WHOQOL-Bref as a starting point for discussion. It works to
      determine important health-related quality of life domains and items within each
      domain, and evaluate issues pertinent to the Palestinian population's
      understanding of life quality in the Occupied Palestinian Territory. Focus group
      discussions (FGD) were conducted with individuals living in the Gaza Strip and
      Ramallah District of the West Bank. Participants were asked if they understood
      the term QOL; and about the determinants of their own QOL, using open-ended
      questions. Participants were then presented with the WHOQOL-Bref questions and
      requested to assess their relevance and importance in determining their own QOL,
      and encouraged to suggest additional ones. A total of 150 men and women of
      various ages and socioeconomic classes participated in 13 FGD. A major finding is
      the all-encompassing impact of the political context on Palestinians' QOL
      assessment. The study demonstrates that political freedom, self-determination,
      participation in democratic processes and feeling involved in political decision
      making are considered important contributors to people's QOL. The study raises
      the option of adding a new domain to the WHOQOL-Bref, allowing the study of its
      psychometric properties and its relationship to the rest of the instrument. This
      contribution should be particularly relevant to societies and cultures in
      conflict-affected zones and locales where violence and insecurity constitute an
      important part of life. The documentation of QOL, beyond fatal and non-fatal
      health outcomes, must remain an important objective of all evaluations in order
      to guide policy and resource allocation decisions directed towards improving
      peoples' lives in general and their health in particular.

PMID- 16797777
TI  - When transcription and repair meet: a complex system.
AB  - Transcription-coupled repair (TCR) is a mechanism that removes DNA lesions so
      that genes can be transcribed correctly. However, the sequence of events that
      results in a DNA lesion being repaired remains elusive. In this review, we
      illustrate the potential chain of events leading to the elimination of the
      damaged DNA and the proper resumption of transcription. We focus on the roles of
      CSA and CSB proteins, which, when mutated, impair TCR. Defective TCR is one of
      the features of Cockayne syndrome, a DNA-repair disorder.

PMID- 16797778
TI  - The coordinated evolution of yeast proteins is constrained by functional
      modularity.
AB  - Functional modularity is a key attribute of cellular systems and has important
      roles in evolution. However, the extent to which functional modularity affects
      protein evolution is largely unknown. Here, we analyzed the evolution of both
      sequence and expression level of proteins in the yeast Saccharomyces cerevisiae
      and found that proteins within the same functional modules evolve at more similar
      rates than those between different modules. We also found stronger co-evolution
      of expression levels between proteins within functional modules than between
      them. These results suggest that a coordinated evolution of both the sequence and
      expression level of proteins is constrained by functional modularity.

PMID- 16797779
TI  - Efficacy and safety of gefitinib in chemonaive patients with advanced non-small
      cell lung cancer treated in an Expanded Access Program.
AB  - Chemotherapy (CT) is recommended in numerous clinical guidelines for advanced non
      small cell lung cancer (NSCLC) and offers improved survival over best supportive
      care. However, many patients with advanced NSCLC never receive CT because of
      advanced age, poor performance status, comorbidities, or patient refusal. The
      epidermal growth factor receptor tyrosine kinase inhibitor gefitinib has shown
      antitumor activity and a favorable toxicity profile in pretreated patients with
      recurrent advanced NSCLC and was made available in a worldwide Expanded Access
      Program (EAP) to >37,000 patients who did not respond to standard treatment or
      were ineligible for or refused CT. A retrospective chart review of 1671
      consecutive patients enrolled at 11 sites in the US arm of the EAP identified 198
      patients with advanced NSCLC who had not received previous CT. All patients were
      treated with gefitinib 250 mg/d until treatment failure or toxicity occurred.
      Patients were treated for a mean of 4.7 months. The most common adverse events
      were diarrhea (31.3%) and rash (31.3%). Complete and partial response rates were
      0.7 and 5.6%, respectively, and 40.6% had stable disease. Median survival was 6
      months, and estimated 1-year survival was 29.7%. The majority of patients did not
      receive subsequent CT.

PMID- 16797780
TI  - Prefrontal activity during flavor difference test: application of functional near
      infrared spectroscopy to sensory evaluation studies.
AB  - Sensory evaluation (SE) of food attributes involves various levels of cognitive
      functions, yet not much has been studied about its neural basis. Using multi
      channel functional near-infrared spectroscopy (fNIRS), we examined the activation
      of the anterior portion of the lateral prefrontal cortex (LPFC) of 12 healthy
      volunteers during the SE of tea samples. The experimental task used corresponded
      to the early phase of the same-different test, and required subjects to
      attentively taste tea samples and memorize their flavors. To isolate activation
      associated with the cognitive functions involved in the task, we contrasted the
      results with those achieved by a control (Ctl) task during which subjects held
      familiar tea samples in their mouths without actively evaluating their flavor. We
      probabilistically registered the fNIRS data to the Montreal Neurological
      Institute standard brain space to examine the results as they correspond with
      other published neuroimaging studies. We found significant activation in the left
      LPFC and in the right inferior frontal gyrus. The activation pattern was
      consistent with earlier studies on encoding of other sensory stimuli, with
      cortical regions supposed to be involved in semantic and perceptual processing.
      This research makes a start on characterizing the cognitive process employed
      during SE from the neuroimaging perspective.

PMID- 16797781
TI  - Discovery of a novel class of conotoxin from Conus litteratus, lt14a, with a
      unique cysteine pattern.
AB  - Conus litteratus is a worm-hunting cone snail with a highly sophisticated
      neuropharmacological defense strategy using small peptides in its venom. By
      analyzing different clones in the cDNA library of venom ducts from C. litteratus,
      we identified the peptide lt14a which displays a characteristic signal peptide
      sequence in its precursor and a unique arrangement of Cys residues (-C-C-C-C-) in
      its mature peptide region. RT-PCR analysis suggested that lt14a is abundantly
      expressed throughout the whole venom duct. An intensive analysis in sequence
      suggested that lt14a is similar to alpha-conotoxin qc1.1 cloned from Conus
      quercinus. We conducted the chemical synthesis of lt14a. The synthetic lt14a has
      a remarkable biological activity to suppress pain and inhibits the neuronal-type
      nicotinic acetylcholine receptors.

PMID- 16797782
TI  - CGRP stimulates gill carbonic anhydrase activity in molluscs via a common CT/CGRP
      receptor.
AB  - The physiological significance of calcitonin gene-related peptide (CGRP) during
      biomineralization was investigated by assessing the effect of human CGRP on the
      carbonic anhydrase activity in gill membranes of the pearl oyster, Pinctada
      margaritifera. Salmon CT and human CGRP were able to induce a 150% increase of
      the basal activity. No additive effect was observed suggesting that both
      activities are mediated by the same receptor. The CGRP-stimulated effect was
      specific as demonstrated by the inhibition produced by the CGRP antagonist,
      hCGRP8-37. So, CGRP by its specific action on gill carbonic anhydrase controls
      the calcification process, an ancient role both in invertebrates and non
      mammalian vertebrates.

PMID- 16797783
TI  - Bradykinin-related peptides from Phyllomedusa hypochondrialis.
AB  - Bradykinin related peptides (BRPs) present in the water-soluble secretion and
      freshly dissected skin fragments of Phyllomedusa hypochondrialis were
      investigated by mass spectrometry techniques. Eighteen BRPs, along with their
      post-translational modifications, were characterized in the secretion by de novo
      MS/MS sequencing and direct MALDI imaging experiments of the frog skin. These
      molecules revealed strong sequence similarities to the main plasma kinin of some
      mammals and reptiles. Such a diversity of molecules, within the same peptide
      family, belonging to a single amphibian species may be related to functional
      specializations of these peptides and a variety of corresponding receptors that
      might be present in a number of different predators. Also, a novel analog,
      [Val]1,[Thr]6-bradykinyl-Gln,Ser had its biological activity positively detected
      in cell culture expressing the human bradykinin B2 receptor and in guinea pig
      ileum preparations.

PMID- 16797784
TI  - Characterization of the pro-inflammatory signaling induced by protein acetylation
      in microglia.
AB  - Protein acetylation regulates the extent of inflammatory responses and
      disturbances in protein acetylation have been proposed to play an important role
      in inflammatory and neurodegenerative diseases. We have recently observed that
      histone deacetylase inhibitors, such as trichostatin A (TSA) and SAHA, strongly
      potentiate the LPS induced inflammatory response in several rat and mouse
      inflammatory models. Our aim here was to characterise pro-inflammatory signaling
      mediated via increased protein acetylation and protein phosphorylation in
      microglial N9 cells. First we observed that TSA induced pro-inflammatory response
      was independent of the different Toll-like receptors activated, since LPS,
      flagellin and unmethylated CpG oligonucleotides, equally potentiated IL-6
      secretion from N9 microglia. Next we compared the protein acetylation induced
      potentiation to that induced by okadaic acid, a well-known inducer of pro
      inflammatory responses. The time scale of the IL-6 responses showed that the
      effects of okadaic acid were clearly early-response effects appearing as soon as
      6h after exposure, whereas TSA evoked a significant inhibition in IL-6 secretion
      up to 12h but after that it induced an exponential increase in cytokine and
      nitric oxide production up to 24h. It seems that okadaic acid induces an early
      moderate response and TSA a late but exponential potentiation of microglial
      inflammatory responses. The pro-inflammatory responses of TSA and okadaic acid
      were both dependent on NF-kappaB signaling but independent on the DNA-binding
      capacity of nuclear NF-kappaB complexes. Interestingly, we observed that the
      transactivation of the NF-kappaB-Luc reporter gene was clearly activated during
      TSA induced pro-inflammatory potentiation. Our studies imply that the
      potentiation of the inflammatory response by increased acetylation is due to the
      enhancement of transactivation of NF-kappaB driven inflammatory genes. Our
      studies on signaling pathways revealed that PI3K inhibitors LY294002 and
      Wortmannin blocked the TSA induced pro-inflammatory response but surprisingly did
      not affect the okadaic acid induced response. Furthermore, LY294002 did not
      inhibit DNA-binding activity of NF-kappaB but still inhibited NF-kappaB-Luc
      reporter gene transactivation. These results indicate that PI 3-kinase regulates
      the transactivation efficiency of NF-kappaB-dependent transcription rather than
      transduction of NF-kappaB signaling.

PMID- 16797785
TI  - Oxidative stress in a rat model of chronic gliosis.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder characterised by
      abnormal extracellular deposition of a 4 kDa peptide termed beta-amyloid,
      neuronal loss, oxidative stress and chronic astrocytosis and microgliosis, but
      how the latter two features contribute to the progression of the disease is
      poorly understood. We have previously demonstrated in a novel in vivo
      transplantation model that chronic astro- and microgliosis resulted in molecular
      pathology similar to that observed in the Alzheimer's disease brain. We now
      report that these heterotopic, gliotic transplants exhibit prolonged oxidative
      stress, characterised by lipid peroxidation and protein carbonyl formation.
      Furthermore, we demonstrate that dietary additives can elevate endogenous anti
      oxidant defences and reduce oxidative stress without attenuating astro- and
      microgliosis. We also show that administration of ibuprofen through the drinking
      water results in a similar reduction in oxidative stress but with no observable
      effect on glial reactivity. The present study lends support to the notion that
      dietary anti-oxidants and non-steroidal anti-inflammatory drugs may be potential
      preventative agents against some of the pathological processes associated with
      neurodegenerative disease.

PMID- 16797786
TI  - Imaging correlates of posterior cortical atrophy.
AB  - The aim of this study was to compare patterns of cerebral atrophy on MRI, and
      neurochemistry on magnetic resonance spectroscopy (MRS), in patients with
      posterior cortical atrophy (PCA) and typical Alzheimer's disease (AD). Voxel
      based morphometry was used to assess grey matter atrophy in 38 patients with PCA,
      38 patients with typical AD, and 38 controls. Clinical data was assessed in all
      PCA patients. Single voxel (1)H MRS located in the posterior cingulate was
      analyzed in a subset of patients with PCA, typical AD, and control subjects. PCA
      showed a pattern of atrophy affecting occipital, parietal and posterior temporal
      lobes, compared to controls. The pattern was bilateral, but more severe on the
      right. Patients with PCA showed greater atrophy in the right visual association
      cortex than patients with typical AD, whereas those with AD showed greater
      atrophy in the left hippocampus than those with PCA. (1)H MRS suggested loss of
      neuronal integrity and glial activation in subjects with PCA and typical AD. The
      differing patterns of atrophy on MRI suggest that PCA should be considered a
      distinct entity from typical AD.

PMID- 16797787
TI  - Clinical significance of corpus callosum atrophy in a mixed elderly population.
AB  - Corpus callosum (CC) is the main tract connecting the hemispheres, but the
      clinical significance of CC atrophy is poorly understood. The aim of this work
      was to investigate clinical and functional correlates of CC atrophy in subjects
      with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC
      from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the
      normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided
      into five regions. Correlations between the CC areas and subjective memory
      complaints, mini mental state examination (MMSE) score, history of depression,
      geriatric depression scale (GDS) score, subjective gait difficulty, history of
      falls, walking speed, and total score on the short physical performance battery
      (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB,
      and walking speed were identified, and the CC areas were smaller in subjects with
      subjective gait difficulty. The correlations remained significant after
      correction for ARWMC grade. In conclusion, CC atrophy was independently
      associated with impaired global cognitive and motor function in subjects with
      ARWMC.

PMID- 16797788
TI  - Phospholipase D1 is associated with amyloid precursor protein in Alzheimer's
      disease.
AB  - Amyloid precursor protein (APP) is a widely expressed transmembrane protein of
      unknown function that is involved in the pathogenesis of Alzheimer's disease
      (AD). We investigated the involvement of phospholipase D (PLD) in the
      pathophysiology of AD. We showed dramatic upregulation of PLD1 immunoreactivity
      in reactive astroglial cells in brain tissue sections from authentic AD patients.
      Expression and activity of PLD1 were up-regulated in brain tissues from AD
      patients, especially caveolae membrane fraction, compared with those of control
      brains. Interestingly, PLD1 physically interacts and colocalizes with APP and
      caveolin-3. We found that APP was associated with the pleckstrin homology domain
      of PLD1, and the amyloid region of APP interacted with PLD. Elevated expression
      of APP stimulated PLD activity in human astroglioma cells. These results suggest
      that up-regulation of PLD might have a role in the neuronal pathology associated
      with AD.

PMID- 16797789
TI  - 82-kDa choline acetyltransferase is in nuclei of cholinergic neurons in human CNS
      and altered in aging and Alzheimer disease.
AB  - Cholinergic neurons express choline acetyltransferase (ChAT) which synthesizes
      acetylcholine. We show here for the first time that primate-specific 82-kDa ChAT
      is expressed in nuclei of cholinergic neurons in human brain and spinal cord;
      isoform-specific antibodies were used to compare localization patterns and
      temporal expression of the more abundant 69-kDa ChAT and primate-specific 82-kDa
      ChAT in necropsy tissues. The 82-kDa ChAT co-localizes with 69-kDa ChAT in well
      characterized cholinergic areas, but is also found in the claustrum which does
      not contain 69-kDa ChAT. Cholinergic neuron function changes with increasing age
      and are targeted in neurodegenerative diseases such as AD, thus we compared
      expression and subcellular localization of 69- and 82-kDa ChAT in necropsy brain
      samples from control subjects of varying ages and from Alzheimer disease (AD)
      subjects. The 82-kDa ChAT protein was expressed in cholinergic neurons in brain
      from birth until the eighth decade of life and in AD, but the subcellular
      staining pattern and proportion of neurons that were immunopositive changed with
      increasing age and in AD.

PMID- 16797790
TI  - Synthesis of a new series of heterocyclic scaffolds for medicinal purposes.
AB  - A new series of substituted 8-fluro-4H-pyrimido[2,1-b] [1,3]benzothiazole-4-ones
      () substituted 7-methyl-4H-isoxazolo[2,3-a]pyrimidin-4-ones, and substituted 2
      methyl-5,6,7,8-tetrahydro-9H-isoxazolo[2,3-a]pyridopyrimidin-9-ones, compounds I
      VII, have been prepared via condensation of beta-keto esters with 2-aminopyridine
      derivatives, in the presence of polyphosphoric acid. The same technique has also
      been used to prepare diazepine compounds, VIII-X, by condensation of a gamma-keto
      ester with 2-aminopyridine derivatives. Details of synthetic procedures are
      shown. The new compounds have been characterized by elemental analysis, GC-MS, FT
      IR and NMR spectrometry. Antibacterial, antifungal and anticancer (cytotoxic)
      activities, for three of these compounds, have been investigated and are
      presented.

PMID- 16797791
TI  - Synthesis and in vitro activity of a series 1beta-methylcarbapenem derivatives.
AB  - The synthesis of a new series of 1beta-methylcarbapenems having pyrrolidine and
      piperidine moieties is described. Their in vitro antibacterial activities against
      both Gram-positive and Gram-negative bacteria were tested and the effect of
      substituent on the pyrrolidine ring was investigated. A particular compound
      (IIIb) having hydroxypyrrolidine moiety showed the most potent antibacterial
      activity.

PMID- 16797792
TI  - [An epigastralgia and emaciation].

PMID- 16797793
TI  - [Original case report of amyloidosis with pleural involvement: the role of
      echocardiography in the diagnosis].
AB  - INTRODUCTION: Amyloidosis is often difficult to diagnose and cardiac involvement
      worsens the prognosis. CLINICAL CASE: We report the case of a 72-year old man
      consulting for cardiac failure with pleural effusion. A restrictive
      cardiomyopathy was discovered by echocardiography, and amyloidosis was then
      suspected. First histological localization was pleural. Cardiac involvement was
      confirmed. The diagnosis was supported by digestive and cutaneous localizations.
      It was an AL amyloidosis. Treatment with melphalan and dexamethasone allowed
      stabilization during more than six months. DISCUSSION: This is an original case
      report, because of the first clinical signs (cardiac failure), the histological
      proof (pleural histology). Echocardiography is particularly helpful in internal
      medicine.

PMID- 16797794
TI  - [A new case of cerebellar ataxia with anti-GAD antibodies treated with
      corticosteroids and initially seronegative].
AB  - INTRODUCTION: Cerebellar ataxia with antiglutamic acid decarboxylase antibodies
      (GAD-ab) is an exceptional newly recognized autoimmune disorder. The cerebellar
      ataxia may occur in isolation or be associated with stiff man syndrome another
      rare GAD-Ab induced disorder of central nervous system. EXEGESIS: A 38-year-old
      woman with a past history of Graves disease presented with insidious cerebellar
      symptoms including ataxic gait, dysmetria, dysarthria, and oscillopsia. A
      thorough survey of markers of paraneoplastic cerebellar ataxia and collagen
      diseases was negative. Her serum contained high level of GAD-ab (647.2 U/ml) and
      MRI evidenced pure cerebellar atrophy leading to diagnosis of autoimmune
      cerebellar ataxia. Under corticosteroids, cerebellar symptoms partially improved,
      but serum GAD-ab titre dramatically decreased. CONCLUSION: Testing for GAD-ab may
      be indicated in patients with idiopathic cerebellar ataxia, particularly mature
      women with organ-specific autoimmune diseases. Corticosteroids must be started to
      prevent irreversible cerebellar atrophy.

PMID- 16797795
TI  - [Anti PM-Scl antibodies. Study of prevalence and of meaning].
AB  - OBJECTIVE: The purpose of our study is to appreciate the prevalence of antibodies
      anti PM-Scl within the framework of antinuclear antibodies detection and to
      clarify clinical biological and evolutive features associated to these
      antibodies. METHODS: 9,747 consecutive antinuclear testing datas allowed us to
      evaluate anti PM-Scl antibodies frequency. A retrospective analysis of patients
      characteristics was performed to identify clinical, biological and evolutive
      signs associated with this antibody over a five years follow up period. RESULTS:
      Over the 9,747 samples tested for antinuclear antibodies detection, 3,493 (35.8%)
      are positive. An anti ENA activity is observed in 727 (7.5%) cases and anti PM
      Scl in 6 (0.06%). These antibodies are described in systemic sclerosis, myositis
      or overlap syndromes. All theses diseases showed a low evolutivity over the five
      years of follow up. CONCLUSIONS: Low prevalence and possible association with an
      overlap autoimmune syndrome of quite good prognosis are reported with anti PM-Scl
      antibodies.

PMID- 16797796
TI  - [A new case of bat rabies in France].
AB  - INTRODUCTION: Bat rabies represents an emerging zoonosis in Europe and the only
      endemic cause of rabies in France. CASE RECORD: A 29 year-old woman was bitten at
      the hand by a bat. The diagnosis of bat rabies was positive and the viral strain
      was an European Bat Lyssavirus 1a. A combination of rabies vaccine and human
      rabies immune globulin was provided to the patient. DISCUSSION: Any direct
      contact with a bat must be avoided. In case of exposure to bats, the postexposure
      treatment must associate the rabies vaccine and human rabies immune globulin
      because of antigenic diversity of Lyssavirus circulating in bat species.

PMID- 16797797
TI  - Modelling the health-economic impact of the next influenza pandemic in The
      Netherlands.
AB  - To optimally develop or adjust national contingency plans to respond to the next
      influenza pandemic, we developed a decision type model and estimated the total
      health burden and direct medical costs during the next possible influenza
      pandemic in the Netherlands on the basis of health care burden during a regular
      epidemic. Using an arithmetic decision tree-type model we took into account
      population characteristics, varying influenza attack rates, health care
      consumption according to the Dutch health care model and all-cause mortality.
      Actual direct medical cost estimates were based on the Dutch guidelines for
      pharmaco-economic evaluation. In the base-case scenario with no preventive
      measure available and an average influenza attack rate of 30%, 4,958,188
      influenza infections, 1,552,687 GP consultations, 83,515 hospitalizations and
      173,396 deaths will take place in The Netherlands. The burden is highest in
      adults aged 20 to 64 years. If minimizing the total mortality and sustaining
      highest net economic returns is the objective, this group needs to be targeted in
      interventions.

PMID- 16797798
TI  - Immunogenicity and protective efficacy of DnaJ (hsp40) of Streptococcus
      pneumoniae against lethal infection in mice.
AB  - The present study was carried out to evaluate the immunogenicity and protective
      efficacy of DnaJ (hsp40) of Streptococcus pneumoniae, by cloning the full-length
      DnaJ of S. pneumoniae and expressing in heterologous host E. coli BL-21 (DE3).
      PCR amplified DnaJ was ligated in pQE-30 expression vector and subsequently
      transformed in E. coli DH5alpha strain. Cloning of DnaJ was confirmed by double
      digestion and PCR, followed by DNA sequencing. The His-tag containing recombinant
      protein was purified by Ni-NTA affinity chromatography. To determine the
      immunogenicity of DnaJ, the mice (10 mice/group) were immunized by injecting 40
      microg DnaJ protein/mouse i.p. There was a significant increase in IgG titres (2
      x 10(5)) in mice immunized with DnaJ protein. Isotyping studies revealed that
      antibodies produced are predominantly IgG2a type indicating the predominance of
      Th1 response. A significant increase in lymphocyte proliferation was observed in
      mice immunized with DnaJ protein as compared to the control mice. Further, there
      was a significant increase in IL-2 and gamma-IFN levels in culture supernatants
      of splenocytes isolated from immunized mice. To determine the efficacy of DnaJ
      vaccination in eliciting protection, the mice were challenged with 1 x 10(5)cells
      of S. pneumoniae A66 type 3 capsular strain intra-nasally after 7 days of last
      immunization. All the control mice died within 2 days of post-infection, while
      70% of animals immunized with DnaJ survived the lethal challenge by S.
      pneumoniae. The study reveals that immunization of mice with DnaJ elicits
      protective immunity against S. pneumoniae infection.

PMID- 16797799
TI  - Heterogeneity of case definitions used in vaccine effectiveness studies--and its
      impact on meta-analysis.
AB  - In the literature, different definitions of clinical illness cases and
      observation period are used to assess influenza vaccine effectiveness, usually
      without addressing their actual specificity and sensitivity. These properties,
      however, have large implications on influenza vaccine effectiveness estimates in
      single trials and meta-analyses of trials. Re-arranging 30 trials (in 17
      publications) with a total of 29,265 subjects according to specificity and
      sensitivity of their case definitions and observation periods, resulted in large
      differences between vaccine effectiveness estimates for various levels of
      specificity and sensitivity. For highly specific definitions the combined vaccine
      effectiveness estimate was 54%, but for highly sensible definitions only 11%.
      Such findings call for a cautious interpretation of combined vaccine
      effectiveness estimates. Internationally agreed case and observation period
      definitions would be desirable to facilitate future meta-analyses.

PMID- 16797800
TI  - Active metabolite from Tamiflu solution is bioequivalent to that from capsule
      delivery in healthy volunteers: a cross-over, randomised, open-label study.
AB  - The bioavailability of oseltamivir phosphate and oseltamivir carboxylate were
      assessed in healthy volunteers when delivered as a solution of the active
      pharmaceutical ingredient (API) compared with the commercial capsule formulation.
      The 90% confidence intervals (CIs) for the ratios of the two treatments (capsule
      versus solution) were within the reference region [0.80-1.25] for area under the
      curve (AUC(0-infinity): [0.94-0.99]) and maximum observed plasma concentrations
      (C(max): [0.93-1.08]). Thus, the two formulations were bioequivalent for
      oseltamivir carboxylate. For pandemic stockpiling of Tamiflu, governments can
      therefore choose between the capsule formulation alone, the API alone, or
      quantities of both.

PMID- 16797801
TI  - Dynamics of dendritic cell migration and the subsequent induction of protective
      immunity in the lung after repeated airway challenges by nontypeable Haemophilus
      influenzae outer membrane protein.
AB  - To determine the dynamics of dendritic cell (DCs) migration and their role in
      recurrent infections by nontypeable Haemophilus influenzae (NTHi), the migration
      of mature DC into pulmonary lymph nodes (LN) and the development of a P6-specific
      immune response and bacterial clearance in the lung were examined after repeated
      airway challenges with outer membrane protein (OMP) at 1-week intervals in mice.
      Although the migration of mature DC into the pulmonary LN is attenuated after
      repeated airway challenge with OMP, the in vitro P6-specific T cell proliferation
      in the cultured pulmonary LN cells was enhanced and was subsequently linked to
      the development of P6-specific IgA production and the development of protective
      immunity in the airway of mice.

PMID- 16797802
TI  - On the bias in HI titers and how to reduce it.
AB  - HI titers measure anti-HA antibody concentrations in sera. By the way they are
      defined standard titers underestimate the true amounts of antibody. A new
      definition is proposed, the mid-value definition. Under mild conditions mid-value
      titers are on average closer to the true value than standard titers.

PMID- 16797803
TI  - Immune response against grouper nervous necrosis virus by vaccination of virus
      like particles.
AB  - The grouper is a high-value fish in the seafood market. Grouper nervous necrosis
      virus (GNNV) causes mass mortality, near 100% in larvae and juveniles, which has
      great economic impact on the aquaculture of the marine fish. Since vaccination is
      one of the best methods against viral diseases, grouper Epinephelus lanceolatus
      was injected with virus-like particles (VLPs) of GNNV at different dosages and
      injection frequencies. The anti-sera of vaccinated fish were analyzed with
      antigen-capture ELISA to quantify immunization titer. The antibody titers in the
      vaccinated fish increased remarkably within 4 weeks, during which time the
      antibody was definitely capable to neutralize the native virus. With one shot of
      10-250 microg VLPs, the stimulated antibody titer reached a steady saturation
      level in 1 month, among which the titers by one shot of 100 and 250 microg VLPs
      were 13% higher than by 10 microg. Two shots of 10 and 100 microg VLPs increased
      to maximum titer, which was 29% higher than one shot, whereas two shots of 250
      microg VLPs and four shots of 100 microg VLPs dramatically downgraded the titers
      by -23% and -44%, respectively. These results imply that the overdose effects
      occurred in total dosages higher than 200 microg VLPs. The experiments of VLP
      vaccine with adjuvant revealed that the adjuvant is not required for increasing
      the efficacy of the VLP vaccine. Immunization with the VLPs can also stimulate
      fish to produce high antibody titer for more than 5 months, which can be
      correlated to long-term protection. When VLPs are used as vaccine agent, a dosage
      at 1 microg/g of fish body weight is enough to stimulate a full-scale immune
      response.

PMID- 16797804
TI  - Evolution of the susceptibility to antiviral drugs of A/H3N2 influenza viruses
      isolated in France from 2002 to 2005.
AB  - In 2002, prior to the generalization of zanamivir and oseltamivir utilization in
      France, we had decided to test a large panel of influenza strains to establish
      the baseline sensitivity of these viruses to anti-neuraminidase drugs. Since
      2002, routine monitoring of resistance relies mainly on the results of
      neuraminidase enzyme assay. The profile of sensitivity of A/H3N2 viruses has not
      changed during these three influenza seasons. Neuraminidase N2 was shown to be
      more sensitive to oseltamivir carboxylate than to zanamivir. Amongst 788 viruses
      tested, only 10 were found with outliers IC(50) values (seven in 2003, one in
      2004, and two in 2005). After the sequencing of the neuraminidase segment of
      these viruses, seven mutations on the stalk or the head of the glycoprotein
      (A18S, L23F, C42R, R143V, E199K, S332K, R431N) were detected. Moreover during
      seasons 2003-2005, 12 additional viruses were characterized by a complete lack of
      neuraminidase activity. In these viruses, viral resistance to NA inhibitors can
      be related with the presence of a defective neuraminidase RNA segment as
      evaluated by a plaque reduction assay, these viruses having a reduced dependence
      on its neuraminidase activity.

PMID- 16797805
TI  - Immunogenicity and tolerance of ascending doses of a recombinant protective
      antigen (rPA102) anthrax vaccine: a randomized, double-blinded, controlled,
      multicenter trial.
AB  - BACKGROUND: We report the results of a phase I dose escalation, safety and
      immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax
      vaccine. METHODS: Hundred healthy volunteers were randomized in a 4:1 ratio to
      receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50,
      or 75 microg of rPA102 in 82.5 microg aluminum hydroxide adjuvant at 0, 4, and 8
      weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4.
      FINDINGS: Local reactogenicity (mostly pain) was more common with AVA than with
      rPA102 following the first (94.7% versus 44.4%; p < 0.001) and the second (84.2%
      versus 35.4%; p < 0.001) vaccinations. Systemic reactogenicity (mostly headache)
      was more common among rPA102 vaccinees, but only following the first vaccination
      (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA
      antibodies was present after the 2nd and 3rd vaccinations. Two weeks following
      the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin
      neutralization activity (TNA), for the 5, 25, 50 and 75 microg rPA102 and AVA
      groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean
      concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1,
      and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for
      the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were:
      22.9, 104.7, 196.4, and 262.6, respectively. INTERPRETATION: No clinically
      serious or dose-related toxicity or reactogenicity was observed. The TNA response
      after two injections of the 75 microg dose of rPA102 was similar to the response
      after two injections of AVA. The third rPA102 vaccination substantially increased
      the antibody response.

PMID- 16797806
TI  - Use of oseltamivir in Dutch nursing homes during the 2004-2005 influenza season.
AB  - To assess the implementation of guidelines for using neuraminidase inhibitors in
      the control of influenza outbreaks in Dutch nursing homes, data were collected on
      prophylactic and therapeutic use of anti-viral medication, indications for use
      and criteria for prescribing, based on experiences during the influenza season
      2004-2005 in a retrospective cross-sectional survey among Dutch nursing homes
      after the 2004-2005 season. Ninety/194 (49%) participating nursing homes reported
      an outbreak of influenza-like illness; in 57/194 (29%) influenza was laboratory
      confirmed. In 37/57 homes (65%) oseltamivir had been used as prophylaxis.
      Prophylactic use was extended to all residents and staff in 6/37 (16%) of homes,
      but limited in the others. In 9/37 (24%) no staff were issued prophylaxis. Among
      clinicians with laboratory confirmed influenza, 41/46 (89%) had used oseltamivir
      therapeutically. Main reasons for not prescribing oseltamivir for prophylaxis
      and/or therapy were lack of scientific evidence, high costs, and absent or
      delayed laboratory confirmation. Logistical bottlenecks in diagnosis, cost
      effectiveness concerns, and lack of an evidence-base hamper full integration in
      policy and should be addressed.

PMID- 16797807
TI  - Diversity in adjustment of maltreated children: factors associated with resilient
      functioning.
AB  - Many decades of research indicate that physical abuse and neglect are associated
      with substantial risk for maladaptation across many developmental tasks of
      childhood, adolescence, and adulthood. Recent investigations, however, indicate
      that in spite of elevated risk for negative outcomes, some abused and neglected
      children demonstrate relatively positive adjustment and success in developmental
      tasks. An overview of studies of resilient functioning among maltreated children
      is provided, and results indicate that although a proportion of maltreated
      children do appear to be resilient to harsh and inadequate caretaking, resilient
      functioning might be short-lived and/or limited to single areas of functioning. A
      summary of factors associated with resilient functioning among abused and
      neglected children is provided. Such factors include individual child
      characteristics (e.g., self-regulatory processes), features of the child's family
      context (e.g., supportive parenting), and experiences in the broader environment
      (e.g., close friendships). Methodological considerations and recommendations for
      further research are provided, and implications of this literature for clinical
      and policy applications are presented.

PMID- 16797808
TI  - Social capital, the miniaturisation of community, traditionalism and first time
      acute myocardial infarction: a prospective cohort study in southern Sweden.
AB  - This longitudinal study investigates the impact of social participation, trust
      and the combinations of social participation and trust on the incidence of first
      time acute myocardial infarction (AMI) in the population of Scania, southern
      Sweden. It is based on the cross-sectional 2000 public-health survey in Scania
      with a 59% participation rate and 13,604 participants, and prospective
      morbidity/mortality data collected for three years (January 2000-December 2002).
      The study cohort was followed prospectively to examine first ever AMI. Hazard
      rate ratios (HRR) for first time AMI in the social participation, trust and
      social participation/trust combinations were calculated in a Cox regression model
      with adjustments for age, sex, education, economic stress, daily smoking, leisure
      time physical activity, body mass index (BMI), and self-reported health. The
      prevalence of low social participation was 32.8% among men and 31.5% among women.
      The prevalence of low trust was 40.0% among men and 44.2% among women. The three
      year first time AMI rate was significantly higher among people with higher age,
      low education, daily smoking, poor self-reported health (among men), low social
      participation, and the combinations of low social participation/high trust and
      low social participation/low trust. The results show that low social
      participation but not trust was significantly associated with first time AMI
      after adjustment for age and sex. The positive association between low social
      participation and myocardial infarction remained significant after further
      adjustments for education, economic stress, daily smoking, physical activity and
      BMI, and became not significant only after additional adjustment for self
      reported health, HRR 1.3 (0.9-2.0). High trust in combination with low social
      participation as well as low social capital (low trust/low social participation)
      were significantly associated with AMI, but after multiple adjustments only the
      low social participation/high trust category remained significant, HRR 1.6 (1.0
      2.6).

PMID- 16797809
TI  - Religious involvement and health outcomes among older persons in Taiwan.
AB  - We use data from a nationally representative, longitudinal survey of older
      Taiwanese to examine the relationship between religious involvement-including
      religious affiliation, religious attendance, beliefs, and religious practices-and
      self-reported measures of overall health status, mobility limitations, depressive
      symptoms, and cognitive function; clinical measures of systolic and diastolic
      blood pressure, serum interleukin-6, and 12-h urinary cortisol; and 4-year
      mortality. Frequency of religious attendance shows the strongest, most consistent
      association with health outcomes. But, with only one exception, this relationship
      disappears in the presence of controls for health behaviors, social networks, and
      prior health status. Religious attendance remains significantly associated with
      lower mortality even after controlling for prior self-assessed health status, but
      the coefficient is substantially reduced. Other aspects of religiosity are only
      sporadically associated with health and, in all cases, private religious
      practices and stronger beliefs are associated with worse health; again, this
      relationship disappears after controlling for prior health status. These results
      suggest that reverse causality may partly account for both the positive and
      negative correlations between religiosity and health. We find no significant
      associations between religious involvement and biological markers. Notably, even
      after controlling for prior health, participation in social activities has a more
      robust effect on health than religious attendance. Consequently, we question
      whether the purported health benefits are attributable to religion or to social
      activity in general.

PMID- 16797810
TI  - From a genetic innovation to mass health programmes: the diffusion of Down's
      Syndrome prenatal screening and diagnostic techniques in France.
AB  - Down's Syndrome prenatal diagnostic and screening techniques have spread widely
      in France over the last 30 years and are now part of the routine clinical
      practice of prenatal care. These techniques, which originated in the field of
      genetics, ultrasonography and biochemistry, were the first to provide the
      possibility of choosing the features of the foetus, or at least to reject some of
      its characteristics. They lead to new norms of healthy foetuses and a progressive
      acceptance of medical abortions. The aim of this paper is to understand how the
      use of these tests has been generalised in France despite scientific
      controversies about their risks and ethical questioning about a potential renewal
      of eugenics. It analyses the representations of public needs that have been
      articulated by key players in the scientific and medical fields. This research
      explores political and administrative decision making processes to understand how
      progressively widening public access to prenatal testing has been organised and
      funded. The results highlight the scientific and political role of biomedical
      researchers, the forms of involvement of health authorities and politicians, and
      the passive participation of the vast majority of the users. The paper also
      examines the characteristics of the French health system that facilitated the
      generalised use of the technology.

PMID- 16797811
TI  - Focus group research and "the patient's view".
AB  - A clear emphasis on the patient's view is discernible in the health services
      research literature of the past decades. Such a switch to patients' perspectives
      has been greatly facilitated by a wider acceptance and use of qualitative
      methods. In particular, focus groups are often used to uncover the range and
      depth of experiences of health services users and chronically ill individuals.
      Although this method contributes to a better understanding of patients'
      perspectives and practices, a number of analytical considerations have been
      overlooked. The aim of this paper is to consider how to conceptualise and analyse
      interactions in focus group research. We argue that focus groups are social
      spaces in which participants co-construct the "patient's view" by sharing,
      contesting and acquiring knowledge. Focus groups conducted with home care
      patients in Quebec, Canada (on antibiotic intravenous therapy, parenteral
      nutrition, peritoneal dialysis and oxygen therapy) are used to illustrate three
      interactive processes at work in focus groups: (1) establishing oneself as
      experienced and knowledgeable; (2) establishing oneself as in search of
      information and advice; and (3) validating or challenging one another's knowledge
      claims. We develop an analytical template focused on the subtle dynamics
      underpinning the various and at times competing claims of patients. This template
      acknowledges the processes through which participants attribute authority to the
      claims of others, including the focus group moderator. We find that focus group
      research does not derive epistemological authority simply from the identity of
      its participants. Rather, an emerging consensus about what constitutes the
      patient's view is the result of context-dependent social interactions that need
      to be scrutinised.

PMID- 16797812
TI  - Marital quality predicts hospital stay following coronary artery bypass surgery
      for women but not men.
AB  - This study examined how two indices of spouse support, one relatively general and
      chronic (perceived overall marital quality), and one relatively situation
      specific and acute (spouse support while in the hospital), separately and in
      interaction with patient gender, predict postoperative length of stays following
      major (coronary bypass) surgery. In a sample of 226 male and 70 female patients
      drawn from three hospitals in the San Diego area, California, the results
      indicated that marital quality, in combination with patient gender, predicted
      postoperative lengths of stay, such that relatively poor marital relationships
      elevated risk for longer stays for female but not male patients. Lengths of stay
      for female patients with higher quality marital relationships were similar to
      those of male patients (regardless of marital quality). These results were not
      attributable to any assessed preoperative differences in patient health and were
      independent of perceptions of spouse support received while in the hospital,
      which did not independently predict patients' lengths of stay.

PMID- 16797813
TI  - Social environment and depression among pregnant women in urban areas of
      Pakistan: importance of social relations.
AB  - Aspects of the social environment, including social conditions (socio-economic
      status, household situations, chronic illnesses) and social relations (attitude
      and behaviors of relations) are major determinants of depression among women.
      This study evaluates the relative power of social relations and social conditions
      in predicting depression among pregnant women in Pakistan. In the qualitative
      phase of the study, social environmental determinants were identified through
      literature search, and experts' opinions from psychologists, psychiatrists,
      gynecologists, sociologists and researchers. Along with this, 79 in-depth
      interviews were conducted with pregnant women drawn from six hospitals (public
      and private) and two communities in Karachi, Pakistan. Identified determinants of
      depression were grouped into themes of social conditions and social relations and
      pregnancy-related concerns. In the study's quantitative phase, the relative power
      of the identified themes and categories, based on their scores for predicting
      depression (determined by the Center for Epidemiological Studies-Depression Scale
      (CES-D scale)), was determined through multivariate linear regression. Social
      environmental determinants of pregnant women were described under the themes and
      categories of (1) social relations: involving husband, in-laws and children; (2)
      social conditions: involving the economy, illness, life events, household work,
      environmental circumstances and social problems; and (3) pregnancy-related
      concerns i.e. symptoms of pregnancy, changes during pregnancy, dependency and
      concern for unborn baby. Multivariate analysis found that among these themes,
      social relations and pregnancy-related concerns were significantly associated
      with total CES-D scores. Among the categories besides increasing age and less
      education, husband, in-laws, household work and pregnancy symptoms were
      significantly associated with total CES-D scores. The study highlights the
      importance of social relations compared to social conditions for determining
      depression in pregnant women.

PMID- 16797814
TI  - Hand preference for writing and associations with selected demographic and
      behavioral variables in 255,100 subjects: the BBC internet study.
AB  - In an Internet study unrelated to handedness, 134,317 female and 120,783 male
      participants answered a graded question as to which hand they preferred for
      writing. This allowed determination of hand preference patterns across 7 ethnic
      groups. Sex differences in left-handedness were found in 4 ethnic groups,
      favoring males, while no significant sex differences were found in three of the
      groups. Prevalence of left-handedness in the largest of the ethnic groups (self
      labelled as "White") was comparable to contemporary hand preference data for this
      group [Gilbert, A. N., & Wysocki, C. J. (1992). Hand preference and age in the
      United states. Neuropsychologia, 30, 601-608] but the prevalence of left
      handedness in individuals >70 years of age was considerably higher in the present
      study. Individuals who indicated "either" hand for writing preference had
      significantly lower spatial performance (mental rotation task) and significantly
      higher prevalence of hyperactivity, dyslexia, asthma than individuals who had
      clear left or right hand preferences, in support of Crow et al. [Crow, T., Crow,
      L., Done, D., & Leask, S. (1998). Relative hand skill predicts academic ability:
      global deficits at the point of hemispheric indecision. Neuropsychologia, 36,
      1275-1282]. Similarly, an association of writing hand preference and non
      heterosexual orientation was clearest for individuals with "either" writing hand
      responses. We conclude that contradictions in the literature as to whether or not
      these variables are linked to handedness stem largely from different definitions
      of hand preference. Due to a lack of statistical power in most studies in the
      literature, the "either" hand writing preference group that yielded the most
      salient results in this study is not normally available for analysis.

PMID- 16797815
TI  - Haloperidol targets brain arachidonic acid signaling.

PMID- 16797816
TI  - Circulating levels of soluble CD26 are associated with phobic anxiety in women.
AB  - Dipeptidyl peptidase IV (DPPIV or CD26) is an ubiquitously expressed protease
      that could play a role in the pathogenesis of anxiety in view of its capacity to
      cleave several behaviourally active neuropeptides. Hereto we sought to determine
      the relationship between phobic anxiety, as measured by the Crown-Crisp index,
      and circulating levels of soluble CD26 (sCD26) in a large cohort of 1017 Italian
      women participating in a general health survey. The association between sCD26
      levels and phobic anxiety was tested using simple correlation analysis, linear
      regression and multivariate logistic regression analysis. A highly significant
      inverse association was found between sCD26 concentrations and anxiety scores
      both in simple correlation and linear regression analysis. Compared with subjects
      in the first tertile of sCD26 levels, the age-adjusted odds ratio for scoring
      >/=6 compared to scoring 0 or 1 was 0.31 (95% CI: 0.18-0.74) for the second and
      0.47 (95% CI: 0.34-0.63) for the third tertile. Altogether, our data suggest that
      reduced plasma sCD26 concentrations could be a marker of high levels of phobic
      anxiety in women.

PMID- 16797817
TI  - Quebrachitol (2-O-methyl-L-inositol) attenuates 6-hydroxydopamine-induced
      cytotoxicity in rat fetal mesencephalic cell cultures.
AB  - Naturally occurring plant substances have the potential to prevent oxidative
      damage in various pathophysiological conditions including neurodegenerative
      disorders. Recent findings indicate that impaired energy metabolism plays a
      prominent role in neurodegeneration. The present study investigated whether
      quebrachitol (2-O-methyl-L-inositol) (QCT), a sugar like natural compound that
      was suggested to have both antioxidant and membrane stabilization activity
      prevents the cytotoxic effect of 6-hydroxydopamine (6-OHDA, 200 microM) on
      cultured rat fetal mesencephalic cells. While QCT (0.1-100 microg/ml) produced no
      effect per se on cell viability as measured in the 3[4,5-dimethylthiazole-2il]
      2,5-diphenyltetrazolium bromide (MTT) test, it offered concentration-related
      protection against cell death induced by 6-OHDA. In addition, QCT demonstrated an
      antioxidant activity against 6-OHDA-induced oxidative stress as evidenced by
      reduced formation of nitrite-nitrate and thiobarbituric acid-related substances.
      Fluorescence microscopy using acridine orange/ethidium bromide double staining
      further affirmed the absence of 6-OHDA (200 microM)-induced morphological changes
      characteristic of apoptosis/necrosis in cultures pretreated with QCT (100
      microg/ml). Also, results of tyrosine hydroxylase immunoreactivity indicated that
      6-OHDA induces cell death in mesencephalic cultures affecting both TH+ positive
      and TH- negative (TH+ and TH-, respectively) and QCT pretreatment protects them
      from cell death, in a non-specific manner. Our data indicate that QCT has a
      cytoprotective role due, at least in part, to an antioxidant and free radical
      scavenging mechanism. Furthermore, the study suggests that inositol compounds
      might serve as leads in developing drugs for the treatment of various
      neurodegenerative disorders.

PMID- 16797818
TI  - Effects of zearalenone on in utero development in rats.
AB  - Zearalenone (ZE), an estrogenic mycotoxin produced by Fusarium graminearum or F.
      roseum, is one of the most common contaminants of cereal grains world-wide. The
      objective of this study was to determine the effects of ZE on in utero
      development of rats. Pregnant female Charles River Sprague-Dawley rats were
      gavaged once daily with ZE (in corn oil) at doses of 0, 1, 2, 4, or 8 mg/kg body
      weight on gestation days (GD) 6-19. All females survived to cesarean section on
      GD 20. At cesarean section, reproductive and developmental parameters were
      measured and blood was taken for hormone analysis. Dose-related decreases were
      seen in maternal feed consumption and body weight gain in all treated groups.
      Delayed fetal development was linked to maternal toxicity. Fetal body weight was
      significantly decreased in both sexes in all treated groups. ZE retarded skeletal
      ossification at 4 and 8 mg/kg. Fetal anogenital index (anogenital distance
      normalized for body weight) was increased in all treated groups, indicating an
      androgenic effect of ZE during fetal development. Fetal viability was
      significantly decreased at 8 mg/kg; significant decreases were observed in number
      of viable fetuses, and number of litters totally resorbed. At 4 and 8 mg/kg,
      maternal liver-body weight ratios were significantly increased and organ-brain
      weight ratios for weights of liver, heart, spleen, kidneys, and ovaries were
      significantly decreased. Gonadotropins (LH, FSH, and prolactin) and sex steroids
      (progesterone and estradiol) were analyzed from the blood serum obtained at
      cesarean section. LH in the 0, 1, 2, and 4 mg/kg groups showed minimal variation,
      and slightly increased at 8 mg/kg. FSH was decreased in the 1, 2, and 4 mg/kg
      groups, but the level at 8 mg/kg was slightly higher than the control level.
      Prolactin level was not affected at 1 mg/kg, slightly increased at 2 and 4 mg/kg,
      and significantly increased at 8 mg/kg. Progesterone was decreased at 2, 4, and 8
      mg/kg and the decreases were significant at 2 and 4 mg/kg. Estradiol level was
      not affected at 1mg/kg, but dose-related decreases were observed at 2, 4, and 8
      mg/kg. Only the 8 mg/kg level of estradiol was significantly decreased. In
      summary, ZE was maternally toxic and fetotoxic but not teratogenic. The increased
      anogenital distance observed in male and female fetuses was considered a hormonal
      change rather than a teratologic response. The increased anogenital distance
      indicated an androgenic effect. Based on the dose-related maternal and fetal
      toxicity in all treated groups, the NOEL for reproductive and teratogenic effects
      was less than 1 mg/kg.

PMID- 16797819
TI  - Increased susceptibility of the lungs of hyperthyroid rats to oxidant injury:
      specificity of effects.
AB  - Results from previous studies indicate that hyperthyroidism increases the risk of
      ozone-induced lung toxicity. This observation raised the possibility that
      pulmonary damage from other oxidant substances might be greater in a hyperthyroid
      state. To address this hypothesis, pulmonary responses to crystalline silica, a
      particulate with oxidant properties, were evaluated in normal or hyperthyroid
      adult male rats. To induce a hyperthyroid condition, time-release pellets
      containing thyroxine were implanted subcutaneously; control rats received placebo
      pellets. After 7 days, the animals were exposed to saline or silica (0.1mg/100g
      BW or 1.0mg/100g BW) by intratracheal instillation. Following silica treatment,
      there was a dose-related increase in bronchoalveolar lavage (BAL) albumin levels
      and neutrophil numbers. However, the effects of silica were similar in both
      normal and hyperthyroid rats. These findings were confirmed and contrasted with
      those regarding ozone (1ppm, 4h inhalation) in a subsequent experiment. The
      results indicated that, although exposure to either ozone or silica resulted in
      increases in BAL albumin levels and neutrophil numbers, only responses to ozone
      were enhanced in hyperthyroid rats. These findings suggest that specificity
      exists in regards to the modulation of oxidant-induced lung damage and
      inflammation by thyroid hormones.

PMID- 16797820
TI  - Catechin prevents tamoxifen-induced oxidative stress and biochemical
      perturbations in mice.
AB  - Natural antioxidants like catechin are now known to have a modulatory role on
      physiological functions and biotransformation reactions involved in the
      detoxification process, thereby affording protection from toxic metabolic actions
      of xenobiotics. Reactive oxygen intermediates have been demonstrated to play an
      etiological role in anticancer drug-induced toxicity. This study was performed to
      explore the modulatory and protective effect of catechin on the toxicity of an
      anticancer drug, tamoxifen (TAM) with special reference to protection against
      disruption of glutathione metabolizing and antioxidant enzymes. TAM treatment
      resulted in a significant increase in the lipid peroxidation (LPO), H(2)O(2)
      generation and protein carbonyl (PC) contents in the liver and kidney as compared
      to controls while catechin+TAM-treated group showed significant decrease in LPO
      levels, H(2)O(2) generation and PC contents in liver and kidney when compared
      with TAM-treated group. Non-enzymatic antioxidants like reduced glutathione (GSH)
      and low molecular antioxidants like ascorbic acid (AsA) also showed normalcy due
      to exogenous catechin administration. Catechin pre-treatment showed restoration
      in the level of cytochrome P450 (CYP) content and in the activities of
      glutathione metabolizing enzymes, viz., glutathione-S-transferase (GST),
      glutathione reductase (GR) and glutathione peroxidase (GPx) and other antioxidant
      enzymes such as, glucose-6-phosphate dehydrogenase (G6-PD), catalase (CAT) and
      superoxide dismutase (SOD) in both liver and kidney when compared to TAM-treated
      animals. The results of the study show that catechin supplementation might be
      helpful in abrogation of TAM toxicity during chemotherapy. Additionally, it makes
      it a prophylactic and preventive agent of anticancer drug-induced oxidative
      stress.

PMID- 16797821
TI  - Effects of topical estradiol on the facial skin collagen of postmenopausal women
      under oral hormone therapy: a pilot study.
AB  - OBJECTIVE: To analyze the dermal collagen of 15 postmenopausal women who had
      being treated with systemic estrogen replacement before and after using topical a
      0.01% estrogen treatment. METHODS: Fifteen patients were included in this
      clinical trial using the systemic estrogen therapy for at least 1 year (minimum
      and maximum lengths of therapy were 13 and 40 months, respectively). A facial
      punch was performed in the preauricular area for collecting samples before and
      after the 16 weeks of treatment. Blood samples were also collected for estradiol
      level determination. The morphometric determination of epithelial and dermal
      thickness as well as dermal collagen were measured using a suitable software. The
      paired Student's t-test was used for statistical analysis. RESULTS: The
      epithelial and dermal thickness enhanced after the topic estrogen therapy
      (P<0.01). The amount of collagen significantly increased after 16 weeks of
      treatment (P<0.001). The estrogen levels did not significant increase after the
      topical therapy (P > or = 0.05). CONCLUSION: Our data suggested that topical
      estrogen associated to systemic estrogen therapy seems to increase the expression
      of skin collagen amount, which may prove to be beneficial for the postmenopausal
      facial skin.

PMID- 16797822
TI  - Changes in the rates of caesarean delivery before labour for breech presentation
      at term in France: 1972-2003.
AB  - OBJECTIVE: To describe the changes in the rate of caesarean deliveries before
      labour among women with term breech presentations in France and to identify the
      factors associated with this change over two periods: 1972-1995/1998 and
      1995/1998-2003. POPULATION: The study population consisted of 1479 women with a
      foetus in a breech presentation at term and without any previous caesarean
      delivery, from the population of births in the 1972, 1995, 1998 and 2003 national
      perinatal surveys (N=53136). Data from the 1995 and 1998 surveys were pooled.
      METHODS: The principal endpoint was caesarean delivery before labour.
      Associations between the factors studied and caesarean before labour were
      estimated by odds ratios, both crude and adjusted with a logistic regression
      model. RESULTS: Between 1972 and 2003, the rate of caesareans before labour for
      women with term breech presentations rose sharply (from 14.5% in 1972 to 42.6% in
      1995/1998 and to 74.5% in 2003). Between 1972 and 1995/1998, this increase was
      especially marked among the nulliparous women (16.7% versus 52.9%). From
      1995/1998 to 2003, the increase was greatest for multiparas: in 2003 this rate
      among women with children was close to that for women who had never given birth
      (64.5% and 79.5%, respectively). After adjustment, the factors associated with a
      high rate of caesarean before labour were nulliparity, birth between 38 and 40
      weeks' gestation, birth weight > or =3800g, delivery in the private sector and
      year of delivery. The rate of caesareans before labour was significantly higher
      in 2003 (ORa=19.04 [12.06-30.06]) and in 1995-1998 (ORa=4.30 [2.87-6.47]) than in
      1972. CONCLUSION: The increase in the rate of caesarean deliveries before labour
      in women with term breech presentations was associated principally with changes
      in obstetrical practices.

PMID- 16797823
TI  - Minilaparotomy versus laparoscopy in the treatment of benign adnexal cysts: a
      randomized clinical study.
AB  - OBJECTIVE: To determine advantages and disadvantages of minilaparotomy and
      laparoscopy in managing patients affected by benign adnexal masses. STUDY DESIGN:
      Prospective, randomized, clinical trial on 127 patients affected by adnexal
      cysts. Patients were submitted to adnexal surgery through a laparoscopic or
      minilaparotomy approach on a random basis. RESULTS: Hundred and twenty-seven
      patients were enrolled in the study and randomly assigned to laparoscopy (63
      patients) or minilaparotomy (64 patients). Characteristics of the patients and of
      the cysts were homogeneous between the two groups. No significant differences
      between the two groups were recorded in terms of operative time, intraoperative
      complications, ileus, length of stay and recovery time. The intraoperative
      rupture rate of the cyst was significantly higher in the laparoscopy group only
      in a subgroup of patients affected by cysts greater than 7 cm in diameter
      (p=0.01). Three patients randomized to laparoscopy required conversion to
      laparotomy. Concerning postoperative outcomes, postoperative pain and minor
      complications were significantly less in patients undergoing laparoscopy (p=0.001
      and 0.04). CONCLUSIONS: Operative laparoscopy appears to be the preferable
      approach for the management of adnexal cysts. Minilaparotomy can be considered a
      mini-invasive approach as well, with acceptable operative and postoperative
      outcomes, and is a suitable alternative in case of contraindications to
      laparoscopy.

PMID- 16797824
TI  - An easy-to-use method for detecting fetal hemoglobin--a test to identify bleeding
      from vasa previa.
AB  - BACKGROUND: Vasa previa is a rare but potentially dangerous fetal condition that
      may occur during pregnancy. Ideally, all cases such cases are detected
      antenatally, but many present as late vaginal hemorrhaging. At the current time,
      there is no test for fetal hemoglobin (HbF) in general use. METHODS: A modified
      method of identifying HbF is presented. Five milliliters of 0.14 M NaOH was
      combined with 50 microl of a mixture of fetal and maternal blood. After 2 min, it
      was judged if the solution still had a red tone or not. The sensitivity of this
      method for detecting HbF was assessed. RESULTS: All 15 clinical personnel could
      identify both 69% and 34% HbF mixed with adult hemoglobin (100% sensitivity), 14
      out of 15 could identify 17% HbF (93% sensitivity), and 12 out of 15 could
      identify a mixture containing 8% HbF (80% sensitivity). CONCLUSION: Our rapid,
      simple test for HbF was at least as sensitive as slower, more cumbersome alkali
      denaturation tests in common use. It could prove to be a lifesaving tool in
      ruling out vasa previa bleeding in cases of unclear late pregnancy hemorrhages.

PMID- 16797825
TI  - Efficacy of a single dose of antenatal corticosteroids on morbidity and mortality
      of preterm infants.
AB  - OBJECTIVE: To assess the effectiveness of an incomplete course of antenatal
      corticosteroids (ACS) on neonatal morbidity and mortality of preterm infants.
      METHODS: Preterm infants born at 25-34 weeks' gestational age between January 1,
      1998 and December 31, 2003 were included in this study. Studied infants were
      divided in two groups: the ACS group included those infants who had been exposed
      to a single 12-mg dose of betamethasone before delivery while the control group
      included those infants who had been delivered without any antenatal
      corticosteroids treatment. The most important neonatal outcomes were compared
      between the two groups. RESULTS: One hundred and seventy neonates (41.4%) were
      exposed to one 12-mg dose of betamethasone before delivery, while 241 neonates
      (58.6%) did not receive any antenatal corticosteroids treatment. Mean gestational
      age at delivery (30.4+/-2.4 weeks versus 31.2+/-2.9 weeks, p=0.004) and mean
      birth weight (1375+/-454 g versus 1625+/-580 g, p<0.001) were lower in the ACS
      group. The univariate analysis showed that delivery room intubation and
      respiratory distress syndrome were more frequent in the ACS group and that the
      length of stay was also significantly longer in this group. No differences were
      found concerning survival, neonatal morbidity, need for and duration of
      mechanical ventilation and oxygen therapy. The incidence of major outcomes in
      survivors was also similar. Logistic regression adjusted for gestational age
      showed that the exposure to a single dose of betamethasone before delivery was
      not associated with a significant reduction in the rate of any neonatal outcome.
      We also compared the outcomes in function of gestational age subclasses. In the
      25-27 weeks subgroup, delivery room intubation, surfactant treatment and patent
      ductus arteriosus (PDA) were less frequent in ACS infants; they had also shorter
      ventilation and oxygen duration. In the 30-31 weeks subgroup, ACS infants had a
      lower incidence of mechanical ventilation and a shorter duration of oxygen
      therapy. Finally, no differences were found in the 28-29 weeks subgroup and in
      the 32-34 weeks subgroup. CONCLUSION: Effects of incomplete antenatal
      corticosteroids are variable: they give some benefits to infants of 25-27 weeks
      gestational age, fail to show any difference in outcomes in the 32-34 weeks
      subgroup and are doubtful between these extremes.

PMID- 16797826
TI  - Improved cervical cancer screening in premenopausal women by combination of Pap
      smear and speculoscopy.
AB  - OBJECTIVE: This study was done to evaluate the efficacy of the Pap smear,
      speculoscopy, and a combination of Pap smear and speculoscopy (PapSure
      examination) in pre- and postmenopausal women. STUDY DESIGN: All women were
      screened using the Pap smear and speculoscopy and combination of both (PapSure
      examination) in the multicenter trial. Final diagnosis of each patient was based
      on a histological evaluation of the colposcopic target biopsy. Results were
      analyzed using a proportional comparison test, sensitivity, specificity, and
      predictive value with significance determined at p<0.05. RESULTS: Of 1813 women
      screened, 1701 were eligible for analysis. Two hundred and fourteen women (12.6%)
      received at least one positive screening test result. Of the 1084 colposcopic
      biopsy specimens obtained, 24 showed low-grade squamous intraepithelial lesion
      (LSIL) and 19 high-grade SIL (HSIL). HSIL were considered test-positive. Rate of
      colposcopy was 21.5% (125/582) in the premenopausal group and 63.9% (321/502) in
      the postmenopausal group (p<0.001). For premenopausal women, speculoscopy (75.0%)
      or PapSure (91.7%) provided higher sensitivity than Pap smear (50%) (p<0.05). In
      postmenopausal women, no statistical significance in sensitivity existed between
      PapSure (85.7%) and Pap smear (57.1%). Speculoscopy (96.8%) or PapSure (96.5%)
      had lower specificity than Pap smear (99.6%) (p<0.001). CONCLUSION: PapSure was
      an accurate alternative screening method to Pap smear or speculoscopy for
      cervical intraepithelial lesions because of a significantly higher sensitivity
      along with adequate specificity for premenopausal women; however, PapSure was not
      a more effective cervical screening method for postmenopausal women.

PMID- 16797827
TI  - Is a poor pregnancy outcome related to young maternal age? A study of teenagers
      in Estonia during the period of major socio-economic changes (from 1992 to 2002).
AB  - OBJECTIVE: To assess the risk of low birth weight, preterm birth, stillbirth,
      neonatal and postneonatal death among primiparous teenagers having singleton
      births, compared to a similar group of women aged 20-24 years in Estonia during
      the period of major socio-economic changes. STUDY DESIGN: Registry study using
      the data from the Estonian Medical Birth Registry (EMBR) for years 1992-2002;
      EMBR data were linked with infant deaths in the Estonian Mortality Database.
      Study population included 51,890 women aged 13-24 years, arranged into three
      groups: < or =17, 18-19, and 20-24. Crude odds ratios (OR), adjusted ORs and
      their 95% confidence intervals (CI) for the different outcomes were estimated
      using multiple logistic regression analysis. RESULTS: Compared with women aged 20
      24 years, the risk of low birth weight and preterm birth was higher among
      teenagers. The risk of low birth weight and preterm birth within the study group
      as a whole did not change during the study period. Increased risks in neonatal
      and postneonatal death among younger teenagers of an age of 17 years and less
      seem to be a result of prematurity. CONCLUSIONS: Despite major socio-economic
      changes resulting in improvements in obstetric care and growth in incomes,
      teenagers remained a higher risk group.

PMID- 16797828
TI  - Endometrial brush cytology in the surveillance of post-menopausal patients under
      tamoxifen: a prospective longitudinal study.
AB  - OBJECTIVE: To evaluate cytological sampling of endometrium using Endobrush (Lab
      CCD, Paris, France) in the surveillance of tamoxifen-treated patients. STUDY
      DESIGN: Between February 1995 and October 1997, 687 tamoxifen-treated patients
      had serial ultrasound screening for endometrial pathology. In case of endometrial
      double layer thickness of more than 8mm, a cytological examination of endometrium
      was attempted followed by hysteroscopy and curettage. RESULTS: One hundred and
      eighty-nine patients had abnormal endometrial ultrasound findings. Cytological
      smear was not obtained in 39 patients because of cervical stenosis or pain in 33
      and 6 cases, respectively. One hundred and fifty patients had cytological
      endometrial sampling followed by hysteroscopy and curettage. Cytological and
      histological findings correlated well in 145 cases (141 benign lesions and 4
      endometrial cancers). There were five false positive (four atypia and one
      cancer). All patients remained free of endometrial cancer at 5 years follow-up.
      CONCLUSION: In tamoxifen-treated patients, endometrial cytology was reliable for
      detection of endometrial pathology, and was well accepted by the patients.

PMID- 16797829
TI  - In search of the fusion pore of exocytosis.
AB  - Research on calcium-triggered exocytosis has converged on the fusion pore as a
      critical kinetic intermediate. Using sensitive biophysical methods to record
      signals from living cells in the act of releasing neurotransmitter or hormone has
      provided clues about the structure and composition of fusion pores. The dynamics
      of fusion pore opening, closing, and dilating has revealed how specific proteins
      transduce a calcium binding signal to catalyze membrane fusion. The fusion pore
      determines how rapidly neurotransmitter is expelled from a vesicle into the
      synaptic cleft. This rate places constraints on the form of a synaptic response
      during different modes of release.

PMID- 16797830
TI  - Fish mercury increase in Lago Manso, a new hydroelectric reservoir in tropical
      Brazil.
AB  - It has been frequently demonstrated that mercury (Hg) concentrations in fish rise
      in newly constructed hydroelectric reservoirs in the Northern Hemisphere. In the
      present work, we studied whether similar effects take place also in a tropical
      upland reservoir during impoundment and discuss possible causes and implications.
      Total Hg concentrations in fish and several soil and water parameters were
      determined before and after flooding at Rio Manso hydroelectric power plant in
      western Brazil. The Hg concentrations in soil and sediment were within the
      background levels in the region (22-35 ng g(-1) dry weight). There was a strong
      positive correlation between Hg and carbon and sulphur in sediment. Predatory
      fish had total Hg concentrations ranging between 70 and 210 ng g(-1) f.w. 7 years
      before flooding and between 72 and 755 ng g(-1) f.w. during flooding, but
      increased to between 216 and 938 ng g(-1) f.w. in the piscivorous and carnivorous
      species Pseudoplatystoma fasciatum, cachara, and Salminus brasiliensis, dourado,
      3 years after flooding. At the same time, concentrations of organic carbon in the
      water increased and oxygen concentrations decreased, indicating increased
      decomposition and anoxia as contributing to the increased Hg concentrations in
      fish. The present fish Hg concentrations in commonly consumed piscivorous species
      are a threat to the health of the population dependent on fishing in the dam and
      downstream river for sustenance. Mercury exposure can be reduced by following
      fish consumption recommendations until fish Hg concentrations decrease to a safe
      level.

PMID- 16797832
TI  - GPX1 Pro198Leu polymorphism, interactions with smoking and alcohol consumption,
      and risk for lung cancer.
AB  - We genotyped blood samples from 432 lung cancer cases and 798 persons in a
      comparison group and examined the role of the GPX1 (Pro198Leu, rs1050450)
      polymorphism and interactions with external exposures in the development of lung
      cancer. The incidence rate ratio for lung cancer was 0.60 (95% confidence
      interval: 0.35-1.05) when homozygous carriers of the variant allele were compared
      with the homozygous carriers of the wild type, and the risk for lung cancer was
      significantly lower among participants carrying more variant alleles (p
      trend=0.03). We found stronger associations between several smoking variables and
      alcohol intake and lung cancer risk among GPX1(TT) carriers than among GPX1(CC)
      and GPX1(CT) carriers.

PMID- 16797831
TI  - Outcome of surgery for clinical unilateral T3a prostate cancer: a single
      institution experience.
AB  - OBJECTIVES: The optimal management of locally advanced prostate cancer (cT3) is
      still a matter of debate. The objective of this study is to present 10-year
      outcomes of radical prostatectomy (RP) in unilateral cT3a disease. PATIENTS AND
      METHODS: Between 1987 and 2004, 2273 patients underwent RP at our institution.
      Two hundred and thirty-five (10.3%) patients were assessed as unilateral cT3a
      disease by digital rectal examination. Thirty-five patients who received
      neoadjuvant treatment before surgery were excluded from further analysis. Mean
      follow-up was 70.6 months. Kaplan-Meier survival analysis was used to calculate
      the biochemical progression-free survival (BPFS), clinical progression-free
      survival (CPFS), cancer-specific survival (CSS), and overall survival (OS) rates.
      Cox uni- and multivariate regression analyses were used to identify predictive
      factors in BPFS and CPFS. RESULTS: Clinical overstaging (pT2) occurred in 23.5%.
      One hundred and twelve (56%) patients received adjuvant or salvage therapy. OS at
      5 and 10 years was 95.9% and 77.0%, respectively, and CSS was 98.7% and 91.6%.
      BPFS at 5 and 10 years was 59.5% and 51.1%, respectively, and CPFS was 95.9% and
      85.4%. Margin status was a significant independent predictor in BPFS; cancer
      volume was a significant independent predictor in CPFS. CONCLUSIONS: Clinically
      advanced prostate cancer is still frequently overstaged. In a well-selected
      patient group with locally advanced prostate cancer, RP--with adjuvant or salvage
      treatment when needed--can yield very high long-term cancer control and survival
      rates. Margin status and cancer volume are significant predictors of outcome
      after RP.

PMID- 16797833
TI  - Heavy metals removal from automobile shredder residues (ASR).
AB  - The fate of heavy metals during a separation process for automobile shredder
      residues (ASR) was investigated. A washing method to remove heavy metals from the
      ASR was also investigated. Although the separation process was not designed for
      removal of heavy metals, but for the recovery of reusable materials, the heavy
      metal content in the ASR was efficiently decreased. The concentrations of Pb, Cr
      and Cd in ASR were effectively reduced by a nonferrous metals removal process,
      and the As concentration was reduced by the removal of light dusts during the
      separation process. Five heavy metals (As, Se, Pb, Cr, Cd) remaining in the ASR
      after the separation process satisfied the content criteria of the Environmental
      Quality Standards for Soil (EQSS), while the concentrations of As, Se, Pb in the
      leachate from the remaining ASR did not satisfy the elution criteria of the EQSS.
      After additional washing of the remaining ASR with a pH 1 acid buffer solution,
      the As, Se, and Pb concentrations satisfied the EQSS for elution. These results
      indicate that an ASR residue can be safely recycled after a separation process,
      followed by washing at acidic pH.

PMID- 16797834
TI  - Heavy metal sorption by calcium alginate beads from Laminaria digitata.
AB  - Alginate with a high M/G ratio, extracted from Laminaria digitata, was evaluated
      for Cu(2+), Cd(2+) and Pb(2+) sorption in acidic solutions, in the form of
      calcium cross-linked beads. The high M/G ratio of alginate extracted from this
      algal species is most likely the determining factor for the increased adsorption
      capacity of the investigated metals, indicating that the mannuronic acid is
      responsible for the ion exchange mechanism. The data obtained from the batch
      experiments have been interpreted with Langmuir, Freundlich and Sips models. The
      Sips equation provided the best fit with the experimental results, indicating
      sorption sites heterogeneity for the material. The pH was found to have a
      significant effect on the process, with sorption capacity reaching a maximum at
      pH 4.5, indicating a competition mechanism between H(+) and metal ions. Kinetic
      experiments were performed at the optimum pH. For the interpretation of the
      kinetic experiments the Linear Adsorption Model was employed and diffusion
      coefficients were determined. The model fits the experimental data at higher
      concentrations, where the adsorbed quantity remains almost constant. Finally, a
      simplified expression of the batch kinetic adsorption model was employed. The
      model, predicts adequately, not only the diffusivity values, but also the
      concentration profiles inside the spherical particles.

PMID- 16797835
TI  - The removal of anionic dyes from aqueous solutions in the presence of anionic
      surfactant using aminopropylsilica--a kinetic study.
AB  - In this study, the aminopropyl-silica (Sil-NH(2)) was used to adsorb a yellow-
      and a red-dye from aqueous solutions at pH 4.0. New data concerning the influence
      of the anionic surfactant SDS on the adsorption data was obtained. All
      interactions occurred below the cmc values of the Sil-NH(2)/anionic dyes
      aggregates. A rise of temperature accelerates the mass transfer of the red-dye
      into the Sil-NH(2) surface, while the yellow-dye adsorption decreased. The
      presence of SDS increased the adsorption quantities in relation to the
      temperature increasing. The exception is observed for the yellow-dye adsorption
      at 55 degrees C. So, it is suggested that the chemical structure of the dye, as
      well as the presence and position of its sulfonate groups are important factors
      that affect the anionic dye/SDS aggregations and the adsorption quantities. The
      solid-phase interactions of dyes data present good fittings to the Avrami kinetic
      model, where from two to four kinetic regions were found, taking into account the
      variations of the contact time and temperature. The presence of several values of
      Avrami constants, namely k(Av) and n, has been attributed to the occupation of
      both the surface and the internal adsorption sites of the aminopropyl-silica.

PMID- 16797837
TI  - Selective expression of histamine receptors in rat mesencephalic trigeminal
      neurons.
AB  - The perikarya of sensory neurons of the mesencephalic trigeminal nucleus (MTN)
      receive dense histaminergic hypothalamic innervation. In this study, we examine
      the yet unknown expression and localization of histamine receptors in the rat MTN
      using immunohistochemistry with subtype-specific antibodies. Same as the
      masticatory muscle spindle somata H1 receptors were located along the entire MTN,
      whereas H3 receptors were detected in the caudal pontine part of the nucleus,
      which receives input from periodontal afferents. Most of the immunostained cell
      bodies were surrounded by histidine decarboxylase-, histamine- or vesicular
      monoamine transporter 2-containing pericellular varicose fibers and terminals in
      a basket-like manner. Our results suggest that rat MTN neurons are directly
      influenced by histaminergic descending projections from the hypothalamus. It can
      be inferred that processing of proprioceptive information at the level of the MTN
      is controlled via histamine H1 and H3 receptors through different postsynaptic
      mechanisms.

PMID- 16797836
TI  - Bioremediation of polycyclic aromatic hydrocarbons (PAH) in an aged coal-tar
      contaminated soil using different in-vessel composting approaches.
AB  - The biodegradation of 16 USEPA-listed PAHs (SigmaPAHs) during simulated in-vessel
      composting-bioremediation of an aged coal-tar-contaminated soil amended with
      fresh green waste compost (FGWC) collected from two landfill sites in the United
      Kingdom (UK) were studied over 56 days. The experimental design compared three
      constant temperature profiles (TC=38, 55 and 70 degrees C) with one variable
      temperature profile including treatment at 70 degrees C to comply with regulatory
      requirements (TP1). The highest disappearance of SigmaPAHs was observed in the
      soil amended with FGWC (53.2% and 48.1% SigmaPAHs disappearance in soil amended
      with FGWC-Site 1 and FGWC-Site 2, respectively) containing lower initial organic
      mater (TOM) (Initial TOM(FGWC-Site 1)=25.6+/-0.6%<Initial TOM(FGWC-Site 2)=32.5+/
      0.1%). Compared with previous investigations, higher disappearance of SigmaPAHs
      occurred when the same coal-tar soil was amended with fresh green waste (56.0%
      SigmaPAHs disappearance in soil amended with fresh green waste) instead of FGWC.
      Using a constant TC1=38 degrees C resulted in a higher disappearance of SigmaPAHs
      when compared to other temperature treatments. However, using a variable
      temperature profile TP1 during in-vessel composting of a soil amended with fresh
      green waste is required to promote contaminant degradation and pathogen control.

PMID- 16797838
TI  - Static postural control in children with developmental dyslexia.
AB  - The present investigation tries to better understand potential association and
      causal relationship between phonological and postural impairment due to
      developmental dyslexia. The study included 50 boys with developmental dyslexia
      and selected on the basis of their overall reading difficulties, and 42 control
      boys. Body sway during a quite standing posture eye open and eye closed on a
      force platform were tested in the two groups of subjects that were between 10 and
      13 years of age. Analysis of classical parameters quantifying the centre of
      pressure (CP) displacements along antero-posterior and lateral axes showed a
      significant difference between the two groups. Dyslexic children showed on
      average greater instability, with greater length, variability and mean power
      frequency of CP displacements with or without vision. Our results demonstrate
      that postural parameters may discriminate between children with dyslexia and age
      equivalent controls.

PMID- 16797840
TI  - Expression of tumor necrosis factor alpha and neuronal apoptosis in the
      developing rat brain after neonatal stroke.
AB  - Increased expression of tumor necrosis factor alpha (TNFalpha) has been shown in
      adult stroke models. However, its expression and relationship with neuronal
      apoptosis in neonatal rats with transient middle cerebral artery occlusion (MCAO)
      have not been clearly elucidated. We studied the expression and distribution of
      TNFalpha and neuronal apoptosis in a postnatal Day 10 rat MCAO model using
      reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot,
      immunohistochemistry, fluorescence double-labeling, and terminal deoxynucleotidyl
      transferase biotin-dUTP nick end labeling (TUNEL) analyses. We found TNFalpha
      mRNA expression increased at 2h and was maintained at high levels until 24h after
      reperfusion. TNFalpha protein expression was significantly increased from 4 to 8h
      (p < 0.01) lasting through 24h (p < 0.05) after reperfusion compared to the sham
      controls. TNFalpha immunoreactive cells were colocalized to neurons in both the
      core and the penumbra areas of the ischemic cortex. However, apoptotic cells were
      mainly distributed in the penumbra area and colocalized to neurons as well as to
      TNFalpha immunoreactive cells in the ischemic cortex. Our findings suggest that
      TNFalpha expression increases after neonatal stroke and is associated with
      neuronal apoptosis after transient focal cerebral ischemia.

PMID- 16797839
TI  - Effects of tarantula toxin GsMTx4 on the membrane motor of outer hair cells.
AB  - GsMTx4, a cationic hydrophobic peptide isolated from tarantula venom, is a
      specific inhibitor of stretch-activated channels (SACs). Here, we show that the
      toxin also affects the membrane motor of outer hair cells at low doses. The
      membrane motor of outer hair cells is based on prestin, a member of the SLC26
      family of membrane proteins, and directly uses electrical energy available at the
      plasma membrane. It is considered to be an essential part of the "cochlear
      amplifier," which increases the sensitivity, tuning, and dynamic range of the
      mammalian ear. The toxin shifts the operating point of the motor. The saturating
      value of the voltage shift is (26 +/- 1) mV, capable of significantly reducing
      the performance of the cochlear amplifier. The dissociation constant is (3.1 +/-
      0.6) microM, about five-fold higher than that for SACs.

PMID- 16797841
TI  - Effects of electroconvulsive seizures on Na(+),K(+)-ATPase activity in the rat
      hippocampus.
AB  - Although several advances have occurred concerning the use of electroconvulsive
      therapy, little progress has been made in understanding the mechanisms underlying
      its therapeutic or side effects. Na(+),K(+)-ATPase is an important enzyme of
      central nervous system, responsible for ionic gradient maintenance and
      consumption of approximately 40-50% of brain ATP. This work was performed in
      order to determine Na(+),K(+)-ATPase activity after acute and chronic
      electroconvulsive shock. Results showed an inhibition of Na(+),K(+)-ATPase
      activity in the hippocampus 48 h, 7, 30, 60 and 90 days after a single
      electroconvulsive shock. Chronic treatment diminished the enzyme activity in the
      hippocampus 7 and 30 days after electroconvulsive (ECS) sessions. Our findings
      demonstrated that Na(+),K(+)-ATPase activity is altered by ECS.

PMID- 16797842
TI  - Deep brain stimulation for chronic neuropathic pain: long-term outcome and the
      incidence of insertional effect.
AB  - We conducted a retrospective analysis of long-term results of deep brain
      stimulation (DBS) for the treatment of neuropathic pain. Twenty-one patients had
      electrodes implanted in the ventrocaudalis thalamic nucleus (Vc) (n=13) or in
      both Vc and periaqueductal/periventricular gray matter (PAG/PVG) (n=8). After
      insertion of the electrodes, 9 patients (43%) had a substantial reduction in pain
      scores in the absence of stimulation (insertional effect). The effects of
      stimulation were studied right after surgery or upon return of the patients' pain
      after electrode insertion (stimulation trials). Patients with a greater than 50%
      reduction in pain scores were implanted with a pulse generator (IPG). Of
      interest, patients who had an insertional effect had a trend towards a successful
      stimulation trial (p=0.08). Overall, 13 of the 21 patients operated (62%) had a
      successful stimulation trial and received an IPG (12 with electrodes in Vc and
      one in both Vc and PAG/PVG). Seven patients (33%) did not benefit from
      stimulation and had the electrodes removed. One patient experienced a prolonged
      insertional effect and has not required stimulation. Of the 13 patients that
      received an IPG, 8 discontinued stimulation during the first year of treatment.
      Only 5 patients maintained long-term benefit (4 with stimulation in Vc and one in
      both Vc and PAG/PVG). The relatively low efficacy of DBS for the treatment of
      neuropathic pain stresses the need for further investigation and the exploration
      of new surgical targets.

PMID- 16797843
TI  - Response of four indigenous cattle breeds to natural tsetse and trypanosomosis
      challenge in the Ghibe valley of Ethiopia.
AB  - A comparative study on the response of four indigenous cattle breeds of Ethiopia,
      namely Abigar, Horro, Sheko and Gurage, to natural challenge of trypanosomosis in
      the Tolley-Gullele area of the Ghibe valley has been undertaken from August 2000
      until August 2004. Fifty female yearlings each of Horro, Sheko and Abigar and 31
      of the Gurage were purchased from their natural habitats and introduced in to
      medium to high tsetse-trypanosomosis challenge area of the Ghibe valley. While
      the natural habitats of first three breeds are naturally infested with tsetse
      flies and trypanosomosis, that of the Gurage is known to be very minimal, if any,
      and hence the Gurage breed was used in this study as the known susceptible breed.
      During the study animal health, production performance and tsetse fly situation
      were monitored monthly. The Sheko breed has manifested very significantly
      (p<0.001) high overall average packed cell volume (PCV) values (25%) compared to
      that of Abigar (24%), Horro (23%) and Gurage (22%). It also had the lowest mean
      trypanosome prevalence rate of 9% against 23% of Horro, 26% of Abigar and 27% of
      Gurage, and the least number of Berenil treatments (1.36) compared to Abigar
      (4.0), Horro (4.6) and Gurage (6.7). While the Abigar manifested high sensitivity
      and frequent death to PCV depression, the Horro showed strong resilience to PCV
      depression and better response to Berenil treatment assistance. At this stage the
      Sheko breed was also found to be equal to the other breeds in its reproductive
      performance. These results need to be substantiated with further in-depth
      investigation including immune response, animal behavior and environmental
      influences.

PMID- 16797844
TI  - Serum antibody isotype responses of Fasciola-infected sheep and cattle to
      excretory and secretory products of Fasciola species.
AB  - This study investigated the immunoglobulin isotype responses of sheep and cattle
      chronically infected with Fasciola hepatica and Fasciola gigantica to adult F.
      hepatica excretory/secretory products (Fh-ES) or F. gigantica excretory/secretory
      products (Fg-ES), respectively. An antibody enzyme-linked immunosorbent assay (Ab
      ELISA) was used to determine serum antibody (total Ig, IgG(1), IgM, IgG(2) and
      IgA) responses. At necropsy, the mean number of flukes recovered was lower in
      cattle than in sheep. All F. hepatica and F. gigantica infected sheep and cattle
      showed an increased total Ig levels from 3 to 4 weeks post-infection (wpi). Among
      isotypes IgG(1) was most dominant while IgM was the earliest (2 wpi) to be
      detected in both sheep and cattle infected with both F. hepatica and F. gigantica
      animals. IgG(2) response was early (2 wpi) in sheep infected by F. hepatica but
      there was no response in sheep infected with F. gigantica. There was a late and
      strong IgG(2) response in cattle infected with both flukes. The IgA isotype
      showed an early and a clear biphasic response in sheep with F. hepatica but was
      less pronounced in F. gigantica infected sheep. While IgA response to Fh-ES was
      noticed 5 wpi in F. hepatica infected cattle, it appeared much later (21 wpi) in
      those infected with F. gigantica. The dominance of IgG(1) isotype in infected
      sheep and cattle suggest an associated Th2 response. This early response to adult
      Fasciola spp. ES antigen suggests an early exposure to the antigen presumably
      through the cross-reacting ES products of juvenile flukes. There is clearly
      difference in IgG(2) isotype response in cattle (resistant) compared to sheep
      (susceptible). The late IgG(2) response in cattle may suggest late Th1
      involvement in bovine cellular responses to adult Fh-ES/Fg-ES.

PMID- 16797845
TI  - Prevalence of Toxoplasma gondii in cats from Colombia, South America and genetic
      characterization of T. gondii isolates.
AB  - Cats are important in the epidemiology of Toxoplasma gondii infection because
      they are the only hosts that can excrete the environmentally-resistant oocysts.
      In the present study, prevalence of T. gondii was determined in serum, feces, and
      tissues of 170 unwanted cats from Colombia, South America. Antibodies to T.
      gondii were assayed by the modified agglutination test and found in 77 of 170
      (45.2%) cats with titers of <1:5 in 93, 1:5 in eight, 1:10 in 17, 1:20 in 10,
      1:40 in seven, 1:80 in four, 1:160 in eight, 1:320 in six, and 1:640 or higher in
      17 cats. T. gondii oocysts were not found in feces of any cat as ascertained by
      bioassay in mice. Tissues (brain, heart, tongue) of 116 cats were bioassayed in
      mice or cats. T. gondii was isolated from tissues of 15 of the 42 cats with
      titers of 1:40 or higher and not from any of the 90 cats titers of 1:20 or lower.
      Of the 29 cats whose tissues were bioassayed individually, T. gondii was isolated
      from the tongues of nine, hearts of eight, and brains of five. Mice inoculated
      with tissues of 12 of 15 infected cats died of toxoplasmosis; with nine T. gondii
      isolates all infected mice died. Overall, 65 of 92 (70%) of T. gondii-infected
      mice died of toxoplasmosis. Genotyping of these 15 isolates using polymorphisms
      at the SAG1, SAG2, SAG3, BTUB, and GRA6 loci revealed that three isolates
      (TgCtCo1, 2, and 7) had Type I alleles and one isolate (TgCtCo8) had Type II
      allele at all five loci. Eleven isolates contained the combination of Type I and
      III alleles and were divided into three genotypes, with TgCtCo3,5,6,9,12,13 and
      15 had alleles I, I, III, I and III, TgCtCo4,10,11 had alleles I, III, III, I and
      I, and TgCtCo14 had alleles I, III, III, III, and III, at loci SAG1, SAG2, SAG3,
      BTUB and GRA6, respectively. All infected mice from each group had identical
      genotype except one mouse infected with TgCtCo5 had a Type III allele at locus
      BTUB and a unique allele (u-1) at locus SAG1 indicating mixed infection for
      TgCtCo5, whereas the rest seven mice had a Type I alleles at both loci.

PMID- 16797846
TI  - Ability of a proteinase inhibitor mixture to kill poultry red mite, Dermanyssus
      gallinae in an in vitro feeding system.
AB  - The development of a reliable in vitro feeding system has enabled the rapid
      testing of presumptive anti-mite factors, a mixture of protease inhibitors (PI),
      by incorporating these into the blood feed. Mites were collected from a caged-hen
      facility and underwent a regime of starvation under varying conditions of
      temperature and darkness to determine the optimum conditions that encouraged
      mites to feed in the in vitro system. The efficacy of two anti-coagulants,
      heparin (HS) and acid citrate glucose (ACD), on mite feeding rates and mortality
      was evaluated. The ability of a mixture of PI to kill mites was also evaluated.
      The rate of feeding was greater in mites that were starved and cooled for between
      7 and 30 days compared with mites that were not starved or cooled. The percentage
      of mites that fed when presented with HS treated blood (70%) was greater when
      compared with ACD treated blood (48%). The mortality of mites fed blood treated
      with HS + PI increased to 45% compared with a mortality level of 5% in mites fed
      on blood treated with HS alone. A reliable in vitro method for feeding D.
      gallinae which has the potential to be used to rapidly screen blood-borne
      products for their efficacy in reducing mite numbers has been developed.

PMID- 16797847
TI  - The impact of daily Duddingtonia flagrans application to lactating ewes on
      gastrointestinal nematodes infections in their lambs in the Netherlands.
AB  - Two experiments were performed in 2002 and 2003 to evaluate the effect of
      biological control of gastrointestinal nematodes in sheep through the daily
      feeding of 500,000 chlamydospores of Duddingtonia flagrans/kg bodyweight to
      lactating ewes during the first 9 weeks with their young lambs on pasture. In
      both experiments four groups of eight ewes and their April-borne lambs were used.
      They were turned out on four separate plots (plots A) at the beginning of May,
      moved to similar separate plots after 3 (plots B) and 6 weeks (plots C),
      respectively, and weaning occurred after 9 weeks. In both experiments, two groups
      were fed spores daily while the two other groups served as controls. The effect
      of D. flagrans application was evaluated through faecal egg counts of ewes and
      lambs, the yield of faecal cultures in ewes, pasture larval counts and worm
      counts of lambs and tracer lambs. The results demonstrated no effect of D.
      flagrans application during the first 5 (2002) or 4 (2003) weeks. Subsequently,
      fungus application strongly reduced the yield in faecal cultures of the ewes.
      This was, however, not reflected in the pasture larval counts, but lower worm
      burdens were observed in tracer lambs of 'treated' plots C in 2002 than on those
      of 'control' plots. In 2003 worm burdens in 'treated' lambs returned to plots B
      were lower than those of 'control' lambs and a tendency for the same was observed
      for plots C. However, in all groups, lambs and tracer lambs developed severe
      haemonchosis.

PMID- 16797848
TI  - Cryptosporidium and Giardia in different age groups of Danish cattle and pigs-
      occurrence and management associated risk factors.
AB  - To obtain information both about the prevalence of Giardia and Cryptosporidium in
      Danish cattle and pigs as well as the possible influence of different management
      systems on the occurrence and intensity of infection, we conducted an
      epidemiological survey comprising 50 randomly selected dairy and sow herds,
      respectively. Each herd was visited once for the collection of faecal samples and
      registration of basic management parameters. Faecal samples were collected from
      three different age groups of animals, i.e. 5 sows/cows, 10 nursing
      piglets/calves less than 1 month, and 10 weaner pigs 8-45 kg/calves 1-12 months.
      The faecal samples were purified and the number of (oo)cysts quantified. The
      study revealed an age-specific herd prevalence of Cryptosporidium of 16, 31 and
      100% for sows, piglets and weaners, respectively, and of 14, 96 and 84% for cows,
      young calves and older calves, respectively. For Giardia the age-specific herd
      prevalence was 18, 22 and 84% for the sows, piglets and weaners, while for cattle
      herds the prevalence was 60, 82 and 100% for cows, young calves and older calves,
      correspondingly. The (oo)cyst excretion levels varied considerably both within
      and between herds for all age groups. Risk factors were evaluated by using
      proportional odds models with (oo)cyst excretion levels divided into four
      categories as response. Among the numerous risk factors examined, only a few were
      demonstrated to have a statistically significant influence, e.g. the use of an
      empty period in the calf pen between introduction of calves for both parasites
      had a protective effect in young calves. For weaners, use of straw in the pen and
      high pressure cleaning between batches of weaners had a preventive effect against
      higher Cryptosporidium oocyst excretion levels.

PMID- 16797849
TI  - Molecular cross-sectional survey of gastric habronemosis in horses.
AB  - Gastric habronemosis of horses caused by Habronema microstoma and Habronema
      muscae (Nematoda, Spirurida) is characterized by catarrhal gastritis, diarrhoea,
      progressive weight loss and ulcers. Despite its importance in the equine industry
      and in clinical practice, knowledge of the epidemiology of this infection is
      still incomplete as diagnosis in live animals is challenging. A two-step semi
      nested PCR assay using ribosomal DNA (rDNA) markers has recently been used for
      the molecular diagnosis in vivo of gastric habronemosis based on the detection of
      H. microstoma and/or H. muscae DNA in equine faeces. To evaluate the field
      efficacy of this assay, a molecular epidemiological survey was carried out on
      equid gastric habronemosis in central Italy. One hundred and fifty-three
      individual faecal samples were collected from live native horses and subjected to
      both coprological examination and the two-step semi-nested PCR. When flotation
      procedures were performed no horse tested positive for Habronema spp. larvated
      eggs while 96 animals (61.2%) were positive for other endoparasites (i.e.
      strongyles, oxyurids, ascarids). Two-step semi-nested PCR detected 86 samples
      (53.6%) that were positive for H. microstoma and/or H. muscae DNA. H. microstoma
      prevalences showed statistically significant differences; the highest prevalence
      was observed in horses infected by other gastrointestinal parasites and
      concomitantly by H. muscae. No statistical differences were found between the
      prevalence of Habronema spp. infection and sex, age, breeding management, and
      antiparasitic treatments. This field survey provided further information on
      habronemosis and its epidemiology.

PMID- 16797850
TI  - Acute changes in the neuronal expression of GABA and glutamate decarboxylase
      isoforms in the rat piriform cortex following status epilepticus.
AB  - The piriform cortex (PC) is the largest region of the mammalian olfactory cortex
      with strong connections to other limbic structures, including the amygdala,
      hippocampus, and entorhinal cortex. In addition to its functional importance in
      the classification of olfactory stimuli, the PC has been implicated in the study
      of memory processing, spread of excitatory information, and the facilitation and
      propagation of seizures within the limbic system. Previous data from the kindling
      model of epilepsy indicated that alterations in GABAergic inhibition in the
      transition zone between the anterior and posterior PC, termed here central PC,
      are particularly involved in the processes underlying seizure propagation. In the
      present study we studied alterations in GABAergic neurons in different parts of
      the PC following seizures induced by kainate or pilocarpine in rats. GABA neurons
      were labeled either immunohistochemically for GABA or its synthesizing enzyme
      glutamate decarboxylase (GAD) or by in situ hybridization using antisense probes
      for GAD65 and GAD67 mRNAs. For comparison with the PC, labeled neurons were
      examined in the basolateral amygdala, substantia nigra pars reticulata, and the
      hippocampal formation. In the PC of controls, immunohistochemical labeling for
      GABA and GAD yielded consistently higher neuronal densities in most cell layers
      than labeling for GAD65 or GAD67 mRNAs, indicating a low basal activity of these
      neurons. Eight hours following kainate- or pilocarpine-induced seizures, severe
      neuronal damage was observed in the PC. Counting of GABA neurons in the PC
      demonstrated significant decreases in densities of neurons labeled for GABA or
      GAD proteins. However, a significantly increased density of neurons labeled for
      GAD65 and GAD67 mRNAs was determined in layer II of the central PC, indicating
      that a subpopulation of remaining neurons up-regulated the mRNAs for the GAD
      isoenzymes. One likely explanation for this finding is that remaining GABA
      neurons in layer II of the central PC maintain high levels of activity to control
      the increased excitability of the region. In line with previous studies, an up
      regulation of GAD67 mRNA, but not GAD65 mRNA, was observed in dentate granule
      cells following seizures, whereas no indication of such up-regulation was
      determined for the other brain regions examined. The data substantiate the
      particular susceptibility of the central PC to seizure-induced plasticity and
      indicate that this brain region provides an interesting tool to study the
      regulation of GAD isoenzymes.

PMID- 16797851
TI  - Suprachiasmatic nucleus communicates with anterior thalamic paraventricular
      nucleus neurons via rapid glutamatergic and gabaergic neurotransmission: state
      dependent response patterns observed in vitro.
AB  - The hypothalamic suprachiasmatic nucleus uniquely projects to the midline
      thalamic paraventricular nucleus. To characterize this projection, patch clamp
      techniques applied in acute rat brain slice preparations examined responses of
      anterior thalamic paraventricular nucleus neurons to focal suprachiasmatic
      nucleus stimulation. Whole cell recordings from slices obtained during daytime
      (n=40) revealed neurons with a mean membrane potential of -66+/-1.2 mV, input
      conductance of 1.5+/-0.1 nS and state-dependent tonic or burst firing patterns.
      Electrical stimulation (one or four pulses) in suprachiasmatic nucleus elicited
      monosynaptic excitatory postsynaptic potentials (mean latency of 12.6+/-0.6 ms;
      n=12), featuring both AMPA and N-methyl-D-aspartate-glutamate receptor-mediated
      components, and monosynaptic bicuculline-sensitive inhibitory postsynaptic
      potentials (mean latency of 16.6+/-0.6 ms; n=7) reversing polarity at -72+/-2.6
      mV, close to the chloride equilibrium potential. Glutamate microstimulation of
      suprachiasmatic nucleus also elicited transient increases in spontaneous
      excitatory or inhibitory postsynaptic currents in anterior thalamic
      paraventricular neurons. Recordings from rats under reverse light/dark conditions
      (n=22) yielded essentially similar responses to electrical stimulation. At
      depolarized membrane potentials, suprachiasmatic nucleus-evoked excitatory
      postsynaptic potentials triggered single action potentials, while evoked
      inhibitory postsynaptic potentials elicited a silent period in ongoing tonic
      firing. By contrast, after manual adjustment of membrane potentials to
      hyperpolarized levels, neuronal response to the same "excitatory" stimulus was a
      low threshold spike and superimposed burst firing, while responses to
      "inhibitory" stimuli paradoxically elicited excitatory rebound low threshold
      spikes and burst firing. These data support the existence of glutamatergic and
      GABAergic efferents from the suprachiasmatic nucleus to its target neurons.
      Additionally, in thalamic paraventricular nucleus neurons, responses to
      activation of their suprachiasmatic afferents may vary in accordance with their
      membrane potential-dependent intrinsic properties, a characteristic typical of
      thalamocortical neurons.

PMID- 16797852
TI  - Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell
      proliferation in the dentate gyrus of adult female rats.
AB  - This study investigated the involvement of estrogen receptors alpha and beta in
      estradiol-induced enhancement of hippocampal neurogenesis in the adult female
      rat. Subtype selective estrogen receptor agonists, propyl-pyrazole triol
      (estrogen receptor alpha agonist) and diarylpropionitrile (estrogen receptor beta
      agonist) were examined for each receptor's contribution, individual and
      cooperative, for estradiol-enhanced hippocampal cell proliferation. Estradiol
      increases hippocampal cell proliferation within 4 h [Ormerod BK, Lee TT, Galea LA
      (2003) Estradiol initially enhances but subsequently suppresses (via adrenal
      steroids) granule cell proliferation in the dentate gyrus of adult female rats. J
      Neurobiol 55:247-260]. Therefore, animals received s.c. injections of estradiol
      (10 microg), propyl-pyrazole triol and diarylpropionitrile alone (1.25, 2.5, 5.0
      mg/0.1 ml dimethylsulfoxide) or in combination (2.5 mg propyl-pyrazole triol+2.5
      mg diarylpropionitrile/0.1 ml dimethylsulfoxide) and 4 h later received an i.p.
      injection of the cell synthesis marker, bromodeoxyuridine (200 mg/kg).
      Diarylpropionitrile enhanced cell proliferation at all three administered doses
      (1.25 mg, P<0.008; 2.5 mg, P<0.003; 5 mg, P<0.005), whereas propyl-pyrazole triol
      significantly increased cell proliferation (P<0.0002) only at the dose of 2.5 mg.
      Our results demonstrate both estrogen receptor alpha and estrogen receptor beta
      are individually involved in estradiol-enhanced cell proliferation. Furthermore
      both estrogen receptor alpha and estrogen receptor beta mRNA was found co
      localized with Ki-67 expression in the hippocampus albeit at low levels,
      indicating a potential direct influence of each receptor subtype on progenitor
      cells and their progeny. Dual receptor activation resulted in reduced levels of
      cell proliferation, supporting previous studies suggesting that estrogen receptor
      alpha and estrogen receptor beta may modulate each other's activity. Our results
      also suggest that a component of estrogen receptor-regulated cell proliferation
      may take place through alternative ligand and/or cell-signaling mechanisms.

PMID- 16797854
TI  - The beneficial effects of high-density lipoprotein on adipocytes may relate to
      its anti-atherogenic properties.
AB  - High-density lipoprotein (HDL) has significant anti-atherogenic properties,
      whereas the underlying mechanisms are complex and have not been completely
      elucidated. Adipocytes produce a variety of adipokines with cardiovascular
      effects. The dysregulated secretion of adipokines by adipocytes may contribute to
      the increased risk of atherosclerosis associated with obesity. Clinical evidences
      indicate that higher plasma HDL-C levels are associated with a favourable
      adipokines secretion profile, suggesting that HDL might improve the dysregulated
      adipokines secretion. HDL may diminish lipid accumulation in adipocytes through
      phosphorylation of PPARgamma and inhibition of aP2 expression, which possibly
      account for the favourable effects of HDL on adipokines secretion. Therefore, we
      hypothesize that HDL might exert several beneficial effects on adipocytes, which
      may relate to its anti-atherogenic properties.

PMID- 16797855
TI  - Mitochondrial dysfunction particularly in adipocytes may be an important
      triggering factor for type 2 diabetes.

PMID- 16797853
TI  - Differences in mitochondrial movement and morphology in young and mature primary
      cortical neurons in culture.
AB  - Mitochondria have many roles critical to the function of neurons including the
      generation of ATP and regulation of intracellular Ca2+. Mitochondrial movement is
      highly dynamic in neurons and is thought to direct mitochondria to specific
      cellular regions of increased need and to transport damaged or old mitochondria
      to autophagosomes. Morphology also varies between individual mitochondria and is
      modulated by fusion and fission proteins such as mitofusin-1 and dynamin-related
      protein-1, respectively. Although mitochondrial movement and morphology are
      thought to be modulated to best meet cellular demands, few regulatory signals
      have been identified. In this study, we examined how the different cellular
      environments of synaptically immature and mature rat cortical neurons affect
      mitochondrial movement, morphology, distribution and function. In younger cells,
      mitochondria were more mobile, were shorter, occupied a smaller percentage of
      neuronal processes, and expressed greater mitofusin-1 and lower dynamin-related
      protein-1 protein levels compared with older cells. However, the number of
      mitochondria per mum of neuronal process, mitochondrial membrane potential and
      the amount of basally sequestered mitochondrial Ca2+ were similar. Our results
      suggest that while mitochondria in young neurons are functionally similar to
      mature neurons, their enhanced motility may permit faster energy dispersal for
      cellular demands, such as synaptogenesis. As cells mature, mitochondria in the
      processes may then elongate and reduce their motility for long-term support of
      synaptic structures.

PMID- 16797856
TI  - Treatment resistance in unipolar depression: Is it an iatrogenic phenomenon
      caused by antidepressant treatment of patients with a bipolar diathesis?
AB  - Major depressive disorder is a common psychiatric illness that is considered
      generally treatable; however, there are some patients who fail to respond in
      spite of adequate trials of antidepressants. Clinical factors known to contribute
      to treatment resistance include psychiatric and physical comorbidity, undiagnosed
      bipolarity, and treatment non-adherence. There is also emerging evidence that the
      use of antidepressants in some 'unipolar' patients may lead to a pattern of
      progressive diminution of therapeutic response and ultimately treatment
      resistance. A large number of these patients may have a bipolar diathesis even
      though there are no symptoms of hypomanic, manic or mixed episodes. It is
      hypothesized that the widespread and injudicious use of antidepressants in
      patients with a bipolar diathesis might result in treatment-induced resistant
      depression. Furthermore, attempts to manage the antidepressant-led mood
      instability might cause increased utilisation of other psychotropic drugs
      including sedative/hypnotics, neuroleptics and mood stabilisers and contribute to
      polypharmacotherapy.

PMID- 16797857
TI  - How to prevent 'half-bastard' progeny? or An alternative for three-parent babies:
      two-parent babies through transplantation of sperm mitochondria.
AB  - Body development and activity depend on the level of internal energy generation.
      Therefore, unaffected, optimally active mitochondria are indispensable in a
      healthy and vital body. A mutation in the DNA of the semi-autonomous mitochondria
      (mtDNA) may cause an inheritable insufficiency that is due to decreased energy
      generation needed for adequate development. Sperm mitochondria will not enter the
      egg cell during fusion of male and female gametocytes. Since women with mutated
      mtDNA will increasingly know and realize the effect of such mutation in their own
      body, they will more often ask for treatment to stop the effect of such
      inconvenient mutation in their progeny. Thus far, solutions for this problem were
      thought to be: (i) nucleus transplantation just after fertilization into a
      nucleus-free egg cell of a second healthy woman and later (ii) transplantation of
      healthy mitochondria from a second woman into the egg cell before fertilization.
      Although both transplantations create babies with three, instead of two-parents
      that have contributed to the genetic content, in case of the newer mitochondria
      transplantation technique the part of the second woman is somewhat more reduced,
      but still clearly present. Thus, assisted-reproduction techniques that mix egg
      cell mitochondria from two women may create not only 'three-parents' babies, but
      also fears for 'three-parents' babies, since this handling may create non
      scientific problems, especially regarding emotional, ethical, religious and
      juridical aspects of life. Transplantation of healthy sperm mitochondria of the
      partner into the egg cell with insufficient mitochondria is thought to be the
      best solution for this problem, since it may create a 'two-parents' instead of a
      'three-parents' baby. This only implies that at the moment of (successful)
      transplantation the biological dogma is broken that mitochondria are maternally
      inherited: the mitochondria of the maternal line of the woman will have been
      substituted by the mitochondria of the maternal line of the man.

PMID- 16797858
TI  - Application of beta-lactamase-dependent prodrugs in clostridial-directed enzyme
      therapy (CDEPT): a proposal.

PMID- 16797859
TI  - Could treatment with arundic acid (ONO-2506) increase vulnerability for
      depression?
AB  - Arundic acid (ONO-2506) is believed to be neuroprotective because of its actions
      on glia cells; i.e., its inhibitory effects on the synthesis of a calcium-binding
      protein S100B. ONO-2506 is undergoing clinical trials for the treatment of
      patients with stroke and Alzheimer's disease. Recent clinical studies point to a
      pervasive comorbidity of depression with stroke and Alzheimer's disease.
      Previously, S100B has been implicated in the pathobiological mechanisms of
      depression. Preclinical studies have shown that antidepressant treatment
      significantly increases brain S100B. Here we hypothesize that available data that
      link S100B with depression, along with the proposed inhibitory action of ONO-2506
      on S100B synthesis, indicate that this compound could increase vulnerability for
      depression in patients at risk for this disorder, and we propose that evaluation
      of patients with stroke and Alzheimer's disease for the presence of depression
      should be routine in clinical trials employing ONO-2506. Although it may be open
      for discussion whether the neuroprotective effects of ONO-2506 are exclusively
      due to its inhibition of S100B synthesis, the latter action of ONO-2506 warrants
      studies of the effects of this drug in the pathobiology of depression.

PMID- 16797860
TI  - Increased hepatic gluconeogenesis: the secret of Lance Armstrong's success.
AB  - Enormous amounts of lactic acid are produced during endurance sport by muscle
      cells. This metabolite is thought responsible for the muscle pain and the fatigue
      during sport. Its internal removal from the body by enzymatic conversion depends
      mainly on the capacity of the hepatic gluconeogenesis that converts lactic acid
      to glucose. The extraordinary sportive results of the racing cyclist Lance
      Armstrong did us realize that a high capacity of hepatic gluconeogenesis was the
      basis of his success, because it might have provided him with less pain
      complaints caused by lactic acid and with an extra source of energy from lactic
      acid. This enhanced gluconeogenesis can be due to his heavy training program. At
      the age of 12-13 years he daily swam 10,000m and cycled 32km. In later years as
      cyclist his training labour was also more than normal. A constitutional increased
      gluconeogenesis cannot be excluded, because as a boy of 12 years he became
      already fourth in 1500m free style swimming in a contest for swimmers from whole
      Texas. The last argument for an increased gluconeogenesis is that Armstrong in
      October 1996 suffered from an extensively disseminated testicular tumour. This
      large tumour load caused that in the tumour the oxidative (=aerobic) energy
      generation changed into a fermentative (=anaerobic) one. This resulted in a high
      increase of lactic acid that putted up the gluconeogenesis in the liver. We think
      that this stimulated, high level gluconeogenesis remained high in the following
      years, when Armstrong restarted cycling, that it provided him with extra energy
      from lactic acid and with fewer complaints due to the exercise, and that thus
      this was the basis of his success.

PMID- 16797861
TI  - Are New World leishmaniases becoming anthroponoses?
AB  - In the New World, leishmaniases are originally wild exoanthropic zoonoses
      developing in sylvatic ecotopes. For a long time, Leishmania parasites have shown
      a remarkable plasticity to face modifications in their environment. Now, both
      geographical extension and numerical increase of leishmaniasis cases in the New
      World are giving cause for concern. These circumstances might have been provoked
      by the simple invasion of zoonotic foci by humans. However, dramatic evolutionary
      mechanisms are also at work in the New World: (i) the reduction of biodiversity
      associated with anthropogenic environmental changes (deforestation and
      urbanization); and (ii) the subsequent adaptations and interactions of new
      vectors and reservoir hosts at the interface with humans. This paper considers
      that these processes could result in new pathogenic complexes tending to
      synanthropic zoonoses, if not anthroponoses. Increasing man-made risk factors
      could thus possibly make leishmaniases a growing public health concern in the New
      World.

PMID- 16797862
TI  - Dysphagia as a risk factor for sudden unexplained death in infancy.
AB  - The TRIAD of encephalopathy, subdural haemorrhages, and retinal haemorrhages is
      commonly considered diagnostic of Shaken Baby Syndrome, but the original paper
      describes a statistically linked QUADRAD of features, the fourth of which is a
      previous history of feeding difficulties (dysphagia). Recent reviews of giving
      pacifiers (dummies) to infants during sleeping periods have found a significant
      reduction in the incidence of Sudden Infant Death Syndrome. Stimulation of
      swallowing is a possible connection with dysphagia, which is examined here,
      illustrated by a well documented case. Although amniotic fluid passes freely
      through the larynx of fetal mammals during fetal breathing, application of pure
      water to the laryngeal epithelium in infants causes choking and laryngeal
      closure. "Water sensors" in the surface respond to lack of chloride ions and
      adapt very slowly or not at all. Others have found in puppies that following
      application of pure water only 32% resume breathing in less than 30-40s. The rest
      needed at least one saline flush, and some required artificial ventilation in
      addition. These receptors also respond to high potassium concentrations and acid
      or alkaline solutions. Normally, airway closure during swallowing or vomiting
      prevents entry of feed or oesophageal reflux, but in some forms of dysphagia
      leakage can occur, causing paroxysmal coughing, reflex laryngeal closure, and so
      prolonged apnoea. Recently, it has been realised that the TRIAD injuries can also
      result from high intracranial vascular pressures transmitted from intra-thoracic
      pressure surges during paroxysmal coughing, choking, etc. Triggering of such
      pressure surges by dysphagic accidents provides a physiological link to injuries
      commonly considered diagnostic of Shaken Baby Syndrome, completing the
      statistically identified QUADRAD of features. Further dysphagic research might
      reveal predictive factors, and preventative measures such as feeds of optimal pH.

PMID- 16797863
TI  - Normal-tension glaucoma and Alzheimer's disease: hypothesis of a possible common
      underlying risk factor.

PMID- 16797864
TI  - The hematological etiology of osteoporosis.
AB  - In this article we present a new working hypothesis, suggesting that overexertion
      of the hematopoietic system resulting from constant excessive need for blood cell
      production, plays an important role in the etiology of osteoporosis. It is
      generally accepted that the development of osteoporosis in postmenopausal women
      is due to the reduction of estrogen level. However a most striking observation is
      the fact that in the male organism, which has never been protected by high levels
      of estrogen, osteoporosis in senescence is significantly less frequent then in
      the female organism, which has been protected by estrogens for at least 35 years.
      Healthy women loose about 70 ml of blood every month, which adds up to some 850
      ml per year and approximately 30 l over the 35 years of their reproductive life.
      Blood loss intensifies hematopoiesis by increasing the level of hematopoietic
      growth factors while, at the same time, stimulating proliferation of osteogenic
      progenitor cells. Osteogenic activity has, indeed, been detected in the blood of
      bled animals. The chain of events that converts continuous requiremental pressure
      on hematopoiesis into development of osteoporosis may be formulated as follows:
      on the one hand, blood loss creates developmental pressure on the hematopoietic
      system, augments production of hematopoietic growth factors with subsequent
      intensified proliferation of hematopoietic progenitor cells, increases the number
      of hematopoietic cells including osteoclasts, thus intensifying resorption of
      bone tissue and extension of hematopoietic territories. On the other hand, blood
      loss leads to stimulation of bone development, extensive proliferation of
      osteogenic progenitor cells resulting in increased numbers of osteoblasts,
      followed by new bone formation and, at the same time, increased production and
      maturation of osteoclasts which then enter the cycle of bone resorption. The bone
      resorption process itself is characterized by the release of bone morphogenic
      proteins that induce proliferation of osteogenic cells and subsequent production
      of osteoclasts that in their turn enter the cycle of bone resorption. Important
      evidence supporting the substantial role of hematopoietic insufficiency in the
      development of osteoporosis comes from the field of clinical hematology:
      hematological diseases accompanied by chronic anemia, such as beta thalassemia
      major, sickle cell anemia, chronic hemolytic anemia, pernicious anemia, etc., are
      also characterized by the concomitant development of osteoporosis. Patients
      suffering from hemophilia tend to develop osteoporosis as well. The possible role
      of functional interaction between hematopoietic and bone tissues in the
      development of age related osteoporosis is also discussed.

PMID- 16797865
TI  - Cysteamine-related agents could be potential antidepressants through increasing
      central BDNF levels.
AB  - Major depressive disorder (MDD) is a common mental disease, but with an unknown
      etiology. Antidepressants are the main biological treatment for MDD. However,
      current antidepressive agents have a slow onset of effect and a substantial
      proportion of MDD patients do not clinically improve, despite maximal medication.
      Thus, the exploration for new antidepressants with novel strategies may help to
      develop faster and more effective antidepressant agents. Studies in the recent
      decades have demonstrated that antidepressants increase central brain-derived
      neurotrophic factor (BDNF) levels and activating the BDNF-signaling pathway may
      play an important role in their therapeutic mechanism. Cysteamine is a natural
      product of cells and constitutes the terminal region of the CoA molecule. Recent
      work has found that cysteamine and a related agent, cystamine, have
      neuroprotective effects in Huntington's disease (HD) mice, through enhancing
      central BDNF levels. Furthermore, cystamine or cysteamine injection could
      increase serum BDNF levels in wild-type mice as well as HD mice. Since activation
      of the BDNF-dependent pathway plays an important role in the mechanism of
      antidepressant therapeutic action, cystamine or its derivatives could have
      potential antidepressant therapeutic effects. Among these agents, pantethine may
      be one of the most promising agents. It is a naturally occurring compound which
      can be administered orally with negligible side effects, and is metabolized to
      cysteamine. Further evaluation of the therapeutic and toxic effects of these
      cysteamine-related antidepressant agents in MDD animal models is needed before
      any clinical application.

PMID- 16797866
TI  - Rescue treatment and prevention of asthma using magnesium throat lozenges:
      Hypothesis for a mouth-lung biologically closed electric circuit.
AB  - In the rescue treatment of acute asthma, injected and inhalant magnesium are
      relatively weak having demonstrated value only in severe illness, although
      theoretical and laboratory considerations suggest that magnesium should be
      strongly effective as an asthma rescue agent. It was hypothesized that a mouth
      lung biologically closed electric circuit (BCEC) exists capable of nearly
      instantly transporting positively charged magnesium ions from the mouth and
      throat into the lungs. One hundred milligram magnesium (magnesium chloride) 4-g
      throat lozenges producing 100+ mM magnesium ion concentration in saliva were
      tested to determine if they had beneficial effects in asthma rescue and
      prevention. Subjects were selected based solely on need for asthma rescue, and
      lozenges were used as needed. Case histories are presented showing the nearly
      immediate effect of magnesium chloride throat lozenges in terminating and
      preventing asthma attacks. Throat lozenges containing magnesium chloride produced
      much more rapid and stronger benefits than has been reported for inhaled and
      injected magnesium. An added benefit from magnesium chloride lozenge treatment of
      asthma was relaxation. In this first report of its kind, magnesium chloride
      throat lozenges appeared to provide rescue benefits in the treatment of asthma
      equivalent to pharmaceutical asthma drugs. Countering these benefits, strong
      ionic magnesium solutions greatly increase rhinovirus, herpesvirus and Candida
      albicans in vitro, and appear to worsen these infections in humans. Magnesium
      lozenges releasing concentrated magnesium ions appear contraindicated during
      common colds, oral herpes infections, chronic rhinosinusitis, oral and
      respiratory infections in general, and their use must immediately be terminated
      if respiratory or oral symptoms worsen. Double-blind, placebo-controlled,
      clinical trials in people without respiratory or oral infections are needed to
      determine magnesium lozenge safety, and the extent by which drug treatment of
      asthma can be reduced.

PMID- 16797867
TI  - The human erythrocyte has developed the biconcave disc shape to optimise the flow
      properties of the blood in the large vessels.
AB  - The human erythrocyte adopts a distinctive biconcave disc form in vivo. The
      question as to why the red blood cell should have this particular profile remains
      unresolved. It has been suggested that this shape maximises the surface area to
      volume ratio and thus expedites diffusion. This hypothesis, however does not
      stand up to examination. Maximal diffusion occurs in the small vessels. In order
      to pass through the microvasculature the erythrocyte becomes distorted and
      deviates from the biconcave disc shape [Branemark PI, Lindstrom J. The shape of
      circulating blood corpuscles. Biorheology 1963;1:139; Guest MM, Bond TP, Cooper
      RG, Derrick JR. Red blood cells: change in capillaries. Science 1963;142:1319
      21]. Here, it is suggested the haemodynamic factors have dictated the peculiar
      shape of the discocyte. The deleterious nature of turbulent flow on the
      cardiovascular system suggests that the biconcave disc form has evolved out of a
      necessity to maximise laminar flow, minimise platelet scatter which in turn
      suppress atherogenic activity in the large vessels [Yoshizumi M, Abe J, Tsuchiya
      K, Berk BC, Tamaki T. Stress and vascular responses: athero-protective effect of
      laminar fluid shear stress in endothelial cells: possible and mitogen-activated
      protein kinases. J Pharmacol Sci 2003;9:172-6]. The biconcave profile of the
      discocyte means that much of the mass is distributed in the periphery. This
      increases the moment of inertia of the cell and subsequently renders the
      erythrocyte less prone to rotation during flow in the large vessels. Here it is
      suggest that this reduction in rotation promotes laminar flow and discourages
      platelet scattering by minimising the "Eddy currents" and it thus anti
      atherogenic. A number of pathological mutations result in the red blood cell
      adopting a spherical shape as opposed to the biconcave disc profile. The sphere
      has a smaller moment of inertia when compared to the discocyte, as much of the
      mass is distributed round the centre. The spherocyte is hence much more prone to
      rotation during flow in the large vessels. There is evidence to suggest that
      asplenic individuals suffering from spherocytosis are at increased risk of
      atherogenic cerebrovascular and cardiovascular large-vessel disease, when
      compared with their asplenic haematological normal counterparts [Schilling RF.
      Spherocytosis, splenectomy, strokes and heart attacks. Lancet 1997;350:1677-8;
      Robinnette CD, Fraumeni Jr JF. Splenectomy and subsequent mortality in veterans
      of the 1939-1945 war. Lancet 1977;ii:127-9].

PMID- 16797868
TI  - Elimination of cardiac arrhythmias using oral taurine with l-arginine with case
      histories: Hypothesis for nitric oxide stabilization of the sinus node.
AB  - We searched for nutrient deficiencies that could cause cardiac arrhythmias
      [premature atrial contractions (PACs), premature ventricular contractions (PVCs),
      atrial fibrillation, and related sinus pauses], and found literature support for
      deficiencies of taurine and l-arginine. Case histories of people with very
      frequent arrhythmias are presented showing 10-20g taurine per day reduced PACs by
      50% and prevented all PVCs but did not prevent pauses. Adding 4-6g of l-arginine
      immediately terminated essentially all remaining pauses and PACs, maintaining
      normal cardiac rhythm with continued treatment. Effects of taurine useful in
      preventing arrhythmias include regulating potassium, calcium and sodium levels in
      the blood and tissues, regulating excitability of the myocardium, and protecting
      against free radicals damage. Taurine restored energy and endurance in one of the
      cases from a debilitated status to normal. Arrhythmias may also respond to
      taurine because it dampens activity of the sympathetic nervous system and dampens
      epinephrine release. l-arginine may have anti-arrhythmic properties resulting
      from its role as a nitric oxide (NO) precursor and from its ability to restore
      sinus rhythm spontaneously. Endogenous production of taurine and l-arginine may
      decline in aging perturbing cardiac rhythm, and these "conditional" essential
      nutrients therefore become "essential" and require supplementation to prevent
      morbidity and mortality. l-arginine is hypothesized to prevent cardiac
      arrhythmias by NO stabilization of the sinus node. Cardiac arrhythmias having no
      known cause in otherwise healthy people are hypothesized to be symptoms of
      deficiencies of taurine and arginine.

PMID- 16797869
TI  - Bronchial epilepsy or broncho-pulmonary hyper-excitability as a model of asthma
      pathogenesis.
AB  - Over the last 20 years, the prevalence of asthma has nearly doubled in
      industrialized countries. A similar increase has been predicted for the next two
      decades. Asthma is major illness in terms of morbidity and suffering, asthma is
      the leading cause of hospitalizations in children under 15 years of age.
      According to many top experts, asthma is correctly characterized as a syndrome
      rather than disease. This lack of definition for asthma makes the search for a
      cause, prevention and potential cure elusive. Episodic airway obstruction and
      reversible bronchial hyperresponsiveness to non-specific irritants are the major
      symptoms of asthma. Airway inflammation is now widely accepted as the key factor
      underlying the pathogenesis of asthma. However, many patients show no signs of
      inflammation, yet they still have severe airflow limitation and asthma symptoms.
      The primary clinical symptoms of asthma are attacks of shortness of breath,
      wheezing, and coughing resulting from excessive and inappropriate constriction of
      the airway smooth muscle. Our research suggests a possible epileptic or hyper
      excitatory condition of bronchial system in asthma pathogenesis. The paroxysmal,
      spasmodic character of asthma attacks may be similar to seizures. We propose a
      unified pathogenetic mechanism of asthma as a syndrome of inducible or
      genetically predisposed membrane hyper-excitability (bronchial epilepsy).

PMID- 16797870
TI  - Chenodeoxycholic acid reduce bacterial translocation in sepsis.

PMID- 16797871
TI  - Cold climate genes and the prevalence of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2D) is approaching epidemic proportions globally.
      However, some human populations, such as Western-Europeans, have a lower
      prevalence compared with urban or westernized groups with origins in warmer
      climates. To explain this conspicuous trend we have developed a hypothesis
      suggesting that pressure for survival on ancestral Western-Europeans (or on other
      human populations) in extremely cold climates could lead to selection for a
      combination of specific genes or alleles, which we have named cold climate genes,
      promoting adaptation to these condition. The possible molecular basis for the
      effects of these genes could lead to decreasing susceptibility to T2D. The
      possible candidates for cold climate genes have been evaluated from three areas:
      the uncoupling proteins, maternally-transmitted mitochondrial genes, and
      mitochondrial biogenesis. CONCLUSIONS/SIGNIFICANCE: The possible existence of
      cold climate genes can lead to both increased thermogenesis and decreased
      prevalence of T2D. This may help explain the variations in prevalence of T2D in
      different ethnic groups. This consideration suggests testable experimental
      approaches towards prevention and therapies for T2D.

PMID- 16797872
TI  - The roles of Arkadia in renal tubular epithelial to mesenchymal transition.
AB  - The ubiquitin-proteasome pathway (UPP) can regulate the stability of proteins,
      which is regarded as an important mechanism in controlling various biological
      processes. In the pathway, E3 ubiquitin ligases play critical roles in the
      recognition of target proteins and degradation by 26S proteasomes. Arkadia is one
      of the E3 ubiquitin ligases, and recent research has shown that Arkadia amplifies
      TGF-beta signalling through degradation of Smad7. The cellular level of Smad7
      plays an important role in the regulation of Smad-mediated TGF-beta signalling
      during progression of organ fibrosis. Studies indicate that the level of Smad7
      protein expression is decreased in progression of tubulointerstitial fibrosis.
      Moreover, growing evidence suggests renal tubular epithelial to mesenchymal
      transition (EMT) plays a key role in renal tubulointerstitial fibrosis and
      transforming growth factor-beta(1) (TGF-beta(1)) is the most potent inducer that
      is capable of initiating and completing the entire EMT course. Therefore, the
      activation of Smad signalling induced by TGF-beta(1) plays a key role in the
      mechanism of renal tubular EMT, and in this process, Arkadia may has an important
      influence on the mechanism above mentioned through degradation of Smad7.

PMID- 16797874
TI  - Aerosolized VEGF in combination with intravenous magnetically targeted delivery
      of DNA-nanoparticle complex may increase efficiency of cystic fibrosis gene
      therapy.

PMID- 16797873
TI  - Cancer cachexia demonstrates the energetic impact of gluconeogenesis in human
      metabolism.
AB  - A review-based hypothesis is presented on the energy flow in cancer patients.
      This hypothesis centres on the hypoxic condition of tumours, the essential
      metabolic consequences, especially the gluconeogenesis, the adaptation of the
      body, and the pathogenesis of cancer cachexia. In growing tumours the O(2)
      concentration is critically low. Mammalian cells need O(2) for the efficient
      oxidative dissimilation of sugars and fatty acids, which gives 38 and 128 moles
      of ATP per mole glucose and palmitic acid, respectively. In the absence of
      sufficient O(2) they have to switch to anaerobic dissimilation, with only 2 moles
      of ATP and 2 moles of lactic acid from 1 mole of glucose. Since mammalian cells
      cannot ferment fatty acids, in vivo tumour cells completely depend on glucose
      fermentation. Therefore, growth of these tumour cells will require about 40 times
      more glucose than it should require in the presence of sufficient O(2). Since
      lactic acid lowers the intracellular pH, it decreases the activity of pyruvate
      dehydrogenase, stimulates fermentation, and thus amplifies its own fermentative
      production. Compensatory glucose is provided by hepatic gluconeogenesis from
      lactic acid. However, the liver must invest 3 times more energy to synthesize
      glucose than can be extracted by tumour cells in an anaerobic way. The liver
      extracts the required energy from amino acids and especially from fatty acids in
      an oxidative way. This may account for weight loss, even when food intake seems
      adequate. In the liver 6 moles of ATP are invested in the gluconeogenesis of one
      mole of glucose. The energy content of 4 out of these 6 moles of ATP is
      dissipated as heat. This may account for the elevated body temperature and
      sweating experience by cancer patients.

PMID- 16797875
TI  - REMOVED: Antioxidant activity of two wild edible mushrooms Morchella vulgaris and
      Morchella esculenta from north Turkey.
AB  - This article has been removed, consistent with Elsevier Policy on Article
      Withdrawal. Please see . The Publisher apologises for any inconvenience this may
      cause.

PMID- 16797876
TI  - Antimicrobial and free radical scavenging activities of Teucrium montanum.
AB  - The antimicrobial and free radical scavenging activities of petroleum ether,
      chloroform, ethyl acetate, n-butanol and water extracts of Teucrium montanum were
      investigated. Ethyl acetate, chloroform and n-butanol extracts expressed a wide
      range of inhibiting activity against both Gram (+) and Gram (-) bacteria. n
      Butanol extract possessed potent DPPH free radical scavenging activity.

PMID- 16797877
TI  - Detection and functional analysis of an SNP in the promoter of the human ferritin
      H gene that modulates the gene expression.
AB  - The H ferritin promoter spans approximately 150 bp, upstream of the transcription
      start and is composed by two cis-elements in position -132 (A box) and -62 (B
      box), respectively. The A box is recognized by the transcription factor Sp1, and
      the B-box by a protein complex called Bbf, which includes the CAAT binding factor
      NF-Y. In this study we performed a functional analysis of an H ferritin promoter
      allele carrying a G to T substitution adjacent to the Bbf binding site, in
      position -69. In vitro studies with reporter constructs revealed a significantly
      reduced transcriptional activity of this allele compared to that of the w.t.
      promoter that was mirrored by a decrease in Bbf binding. In vivo, this variant
      genotype is accompanied by a reduced amount of the H mRNA in peripheral blood
      lymphocytes.

PMID- 16797878
TI  - Coordinated fibroblast growth factor and heparan sulfate regulation of
      osteogenesis.
AB  - Growth and lineage-specific differentiation constitute crucial phases in the
      development of stem cells. Control over these processes is exerted by particular
      elements of the extracellular matrix, which ultimately trigger a cascade of
      signals that regulate uncommitted cells, by modulating their survival and cell
      cycle progression, to shape developmental processes. Uncontrolled, constitutive
      activation of fibroblast growth factor receptors (FGFR) results in bone
      abnormalities, underlining the stringent control over fibroblast growth factor
      (FGF) activity that must be maintained for normal osteogenesis to proceed.
      Mounting evidence suggests that FGF signalling, together with a large number of
      other growth and adhesive factors, is controlled by the extracellular
      glycosaminoglycan sugar, heparan sulfate (HS). In this review, we focus on FGF
      activity during osteogenesis, their receptors, and the use of HS as a therapeutic
      adjuvant for bone repair.

PMID- 16797879
TI  - Large-scale analyses of synonymous substitution rates can be sensitive to
      assumptions about the process of mutation.
AB  - A popular approach to examine the roles of mutation and selection in the
      evolution of genomes has been to consider the relationship between codon bias and
      synonymous rates of molecular evolution. A significant relationship between these
      two quantities is taken to indicate the action of weak selection on substitutions
      among synonymous codons. The neutral theory predicts that the rate of evolution
      is inversely related to the level of functional constraint. Therefore, selection
      against the use of non-preferred codons among those coding for the same amino
      acid should result in lower rates of synonymous substitution as compared with
      sites not subject to such selection pressures. However, reliably measuring the
      extent of such a relationship is problematic, as estimates of synonymous rates
      are sensitive to our assumptions about the process of molecular evolution.
      Previous studies showed the importance of accounting for unequal codon
      frequencies, in particular when synonymous codon usage is highly biased. Yet,
      unequal codon frequencies can be modeled in different ways, making different
      assumptions about the mutation process. Here we conduct a simulation study to
      evaluate two different ways of modeling uneven codon frequencies and show that
      both model parameterizations can have a dramatic impact on rate estimates and
      affect biological conclusions about genome evolution. We reanalyze three large
      data sets to demonstrate the relevance of our results to empirical data analysis.

PMID- 16797881
TI  - Functional complementation of a nitrate reductase defective mutant of a green
      alga Dunaliella viridis by introducing the nitrate reductase gene.
AB  - Nitrate reductase (NR) catalyzes NAD (P) H dependent reduction of nitrate to
      nitrite. Transformation systems have been established in several species of green
      algae by nitrate reductase gene functional complementation. In this report, an
      endogenous NR cDNA (3.4 kb) and a genomic fragment (14.6 kb) containing the NR
      gene (DvNIA1) were isolated from the D. viridis cDNA and genomic libraries
      respectively. Southern blot and Northern blot analyses showed that this gene
      exists as a single copy in D. viridis and is induced by nitrate. To obtain a NR
      defective mutant as a recipient strain, D. viridis cells were treated with a
      chemical mutagen and then cultured on a chlorate-containing plate to enrich
      chlorate tolerant mutants. Southern analysis showed that one isolate, B14, had a
      deletion in the DvNIA1 gene region. Using electroporation conditions determined
      in this laboratory, plasmid pDVNR containing the intact DvNIA1 gene has been
      electroporated into the defective mutant B14. Strains retaining a nitrate
      assimilation phenotype were obtained from nitrate plates after spreading the
      electroporated cells. In some individual strains, transcription of the introduced
      gene was detected. NR activity in these strains was slightly higher than that in
      the defective B14 cell, but excretion of nitrite into culture media was almost as
      high as that of the wild-type cell. Possible episomal presence of the introduced
      DNA in D. viridis is discussed.

PMID- 16797880
TI  - Role of p38 in stress activation of Sp1.
AB  - Cell stressors such as physical forces can activate Sp1-dependent genes but the
      regulatory mechanisms are not defined. We determined if the stress-induced MAP
      kinase, p38, can phosphorylate Sp1 and thereby regulate the Sp1 target gene FLNA.
      We used Rat-2 cells and human gingival fibroblasts to examine stress-induced
      activation of an Sp1-dependent gene and SL2 cells, an Sp1-deficient model system,
      to facilitate interaction studies of transfected Sp1 with regulatory factors.
      Mechanical stress applied to Rat-2 cells increased promoter activity of the Sp1
      target gene filamin A by >5-fold; activation was blocked by mutations to Sp1
      binding sites in the filamin A promoter. Transfection experiments in SL2 cells
      with Sp1 expression vectors showed that when co-transfected with constitutively
      active p38, wild-type Sp1 but not an Sp1 binding mutant, increased promoter
      activity of the Sp1 target gene, filamin A, and enhanced binding of nuclear
      extracts to a filamin A promoter oligonucleotide. Filamin A promoter activity was
      blocked by dominant negative p38. Sp1 that was phosphorylated at Thr453 and
      Thr739 by constitutively active p38 bound to the filamin A promoter more
      effectively than un-phosphorylated Sp1. Recombinant active p38 phosphorylated
      wild-type Sp1 in vitro while the Sp1 Thr453Thr739 double mutant protein showed >3
      fold reduction of phosphorylation. We conclude that stress activation of p38
      phosphorylates Sp1 at specific threonine residues, modifications which in turn
      enhance the expression of Sp1-dependent genes.

PMID- 16797883
TI  - Molecular characterization of recent Korean porcine reproductive and respiratory
      syndrome (PRRS) viruses and comparison to other Asian PRRS viruses.
AB  - Twenty-eight PRRS viruses (PRRSVs) isolated from various pig farms in Korea
      between 2002 and 2003 were sequenced for open-reading frame (ORF) 5 and/or full
      length genome and compared with numerous PRRSVs reported from North America,
      Europe and Asia. All Korean isolates examined were genetically of the North
      American genotype. The ORF5 sequence of one isolate was identical to Ingelvac
      PRRS MLV vaccine virus. ORF5 nucleotide sequence divergence of the remaining 27
      Korean PRRSVs from VR-2332, the prototype of the North American PRRSV and
      parental strain of the MLV vaccine virus, ranged from 1.3% to 12.9%, which
      corresponded to 2.0% to 14.9% divergence at the amino acid level, raising a
      concern on the efficacy of the MLV vaccine. Phylogenetic analyses of ORF5 and/or
      full-length sequences revealed that the Korean PRRSVs formed a clade distinct
      from PRRSVs reported from other Asian countries (China, Taiwan, Japan, and
      Thailand). Our study demonstrated that PRRSVs of the North American genotype were
      introduced to the Korean swine population some time ago and have evolved
      independently from PRRSV in other Asian countries, suggesting that geographic
      separation might influence the molecular evolution of PRRSV. This should be taken
      into consideration when a national PRRS prevention and control policy for
      international trade is established.

PMID- 16797882
TI  - Full-length sequence and expression analysis of Toll-like receptor 9 in the
      gilthead seabream (Sparus aurata L.).
AB  - Toll-Like Receptors (TLRs) have recently emerged as key sensors of invading
      microbes, acting through recognition of pathogen-associated molecular patterns.
      It has been demonstrated that TLR9 is involved in the recognition of unmethylated
      CpG motifs in mice, humans, and pigs. We report here the full-length sequence of
      TLR9 cDNA in the gilthead sea bream (Sparus aurata L.). The predicted protein
      (1063 amino acids) was similar to mammalian TLR9s, showing 21 leucine-rich
      repeats in the extracellular region and a typical Toll/IL-1R (TIR) domain in the
      intracellular region. Comparative analysis of TLR9 sequences indicated that
      critical residues for ligand-binding are conserved across vertebrate lineages,
      although evidence of functional divergence was observed. Analysis of the genomic
      structure of sea bream TLR9 gene revealed the presence of two intervening
      sequences. Retention of the second intron produced an alternatively spliced mRNA
      (TLR9B) showing differential expression among tissues or developmental stages
      compared to the wild-type isoform (TLR9A). RT-PCR analysis indicated a broad
      expression of TLR9A, especially in immune-related organs (spleen, head-kidney)
      and mucosal-epithelial barriers (gills, gut, skin). Using quantitative Real-Time
      RT-PCR, no statistically significant variation was observed for TLR9 mRNAs
      expression in the spleen of experimentally infected animals compared to healthy
      controls. Comparing sequence and expression profile of sea bream TLR9 with
      mammalian TLR9s suggested that the main function of TLR9 might be conserved
      across vertebrates, although species-specific features are present (modulation of
      ligand-binding specificity, alternative splicing).

PMID- 16797884
TI  - No evidence of bluetongue virus in Switzerland.
AB  - We report the results of the first survey for antibody against bluetongue virus
      (BTV) that was conducted in Switzerland in the year 2003. In a nationwide cross
      sectional study with partial verification, 2437 cattle sera collected from 507
      herds were analysed using competitive enzyme-linked immunosorbent assays (c
      ELISA). To adjust for misclassification, 158 sera, including 86 that were
      recorded equivocal in Switzerland, were sent to the Office Internationale des
      Epizooties designated regional reference laboratory in the UK for confirmation.
      No BTV antibody was detected in any of these samples, confirming the absence of
      BTV from Switzerland in 2003. The specificity of the c-ELISA used in Switzerland
      for individual Swiss cattle was calculated to be 96.5%. The mean herd sensitivity
      achieved in our survey ranged from 78.9% to 98.8% depending on the with-in herd
      prevalence and test sensitivity used for the calculations. The cumulated
      confidence level achieved with the survey based on a minimal expected prevalence
      of 2%, was 99.99% and therefore it was concluded that there was no evidence of
      BTV circulation in Switzerland in 2003.

PMID- 16797885
TI  - Comparative macrorestriction and RFLP analysis of Mycobacterium avium subsp.
      avium and Mycobacterium avium subsp. hominissuis isolates from man, pig, and
      cattle.
AB  - In Germany, tuberculous lesions in slaughtered pigs due to infection with members
      of the Mycobacterium avium complex are increasingly reported. Contaminated food
      originating from pig or other livestock is discussed as potential source of human
      infection. M. avium isolates from man (n=45), pig (n=29), and cattle (n=13) were
      characterised by restriction fragment length polymorphism (RFLP) with respect to
      insertion sequences IS1245 and IS901 as well as by XbaI-based pulsed-field gel
      electrophoresis (PFGE) and the results were compared by computer cluster
      correlation analysis, to determine potential sources of infection in man. By PCR,
      55% of animal isolates was identified as M. avium subsp. avium, and 45% as M. a.
      hominissuis. All human isolates belonged to M. a. hominissuis. IS1245-RFLP and
      PFGE resulted in two distinct main groupings reflecting the two subspecies, and
      dividing the isolates into several subgroups. Animal isolates of M. a.
      hominissuis were widely distributed within the subgroups of human isolates. M. a.
      avium isolates, further discriminated by IS901-RFLP, formed host-associated
      subgroups for animals. Comparison of RFLP patterns with those of PFGE resulted in
      different subgroups as well as different pairs of isolates with high
      similarities. Only two isolates exhibited identical patterns by both methods. In
      general, results of both methods support the possibility that M. a. hominissuis
      isolates from livestock represent a source of infection for man, probably by
      common environmental reservoirs. There was no evidence of human infections caused
      by M. a. avium in Germany.

PMID- 16797886
TI  - A study of zearalenone cytotoxicity on human peripheral blood mononuclear cells.
AB  - The mycotoxin zearalenone (ZEA) is a common contaminant of all major cereal
      grains worldwide with estrogenic and anabolic activity. We investigated the in
      vitro cytopathic effects of ZEA on freshly isolated human peripheral blood
      mononuclear cells (PBMC) in relation to proliferation and cell death patterns of
      untreated and mitogen-activated cells. The higher concentration of 30microg/ml
      ZEA was found to totally inhibit T and B lymphocyte proliferation from the
      stimulation with phytohemagglutinin and pokeweed mitogen. The inhibitory effects
      of ZEA were further related to cell necrosis/apoptosis. Flow cytometry analysis
      showed a distinct necrotic effect on PBMC, irrespective of mitogen stimulation,
      whereas apoptotic activity was less evident. Necrosis was observed in both the
      lymphocyte and monocyte/granulocyte gates. Measurements of ZEA-induced
      intracellular calcium ion (Ca(2+)) mobilization showed an increase of both Ca(2+)
      levels and the number of cells with high Ca(2+) only in the monocyte/granulocyte
      gated cells. Using phenylmethyl sulfonyl fluoride (PMSF), a serine protease
      inhibitor, and ammonium chloride (NH(4)Cl), a lysosomal inhibitor, both
      associated with cell necrosis inhibition, we showed that PMSF at 0.05mM and
      NH(4)Cl at 1 and 10mM reduced the cytopathic effects induced by 30microg/ml ZEA,
      whereas apoptosis was less affected. Expose of PBMC to 1microg/ml ZEA did not
      alter the viability of the cells. Our results suggest that high ZEA
      concentrations in the blood may well exert cytotoxic effects that merit further
      investigation.

PMID- 16797887
TI  - Arsenite induces apoptosis in hepatocytes through an enhancement of the
      activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase
      caused by partial hepatectomy.
AB  - To investigate the effects of arsenite on cell proliferation and the signal
      transduction in hapatocytes in vivo, rats received a single injection of sodium
      arsenite immediately after partial hepatectomy. Characteristic DNA fragmentation
      was observed at 4h after the arsenite-injection in partially hepatectomized
      liver, while it was not detected either in the control (partial hepatectomy only)
      or arsenite-injected normal (without partial hepatectomy) liver. The effect of
      the arsenite-injection on the activation of extracellular signal-regulated kinase
      (ERK) was not observed in the normal or the partially hepatectomized liver. The
      activity of p38 mitogen-activated protein kinase (MAPK) markedly increased after
      15min to 2h after the arsenite-injection in partially hepatectomized liver while
      no or a less increase was observed in the arsenite-injected normal or the
      control, respectively. The Jun N-terminal kinase (JNK) was activated to a maximal
      level, about six-fold the maximum of the control, at 15min after the injection
      with partial hepatectomy. The arsenite-injection markedly increased the
      phosphorylated forms of c-Jun and ATF-2 and the protein levels of c-Jun, p53 and
      p21(WAF1/CIP1) in the partially hepatectomized liver. These results suggested
      that arsenite induced apoptosis in the hepatocytes in vivo, through the
      enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy
      and the p53-dependent p21(WAF1/CIP1) protein expression.

PMID- 16797888
TI  - Inhibition of mammalian target of rapamycin modulates expression of adhesion
      molecules in endothelial cells.
AB  - Neointimal hyperplasia often follows angioplasty-induced arterial injury or
      stenting and results in restenosis. Previous reports have suggested that arterial
      injury activates complement which amplifies inflammatory responses that may
      initiate and sustain neointimal hyperplasia. The effects of rapamycin on
      complement-induced expression of intracellular adhesion molecules (ICAMs) were
      examined in porcine arterial endothelial cell (PAEC) line that was transformed
      with large T antigen. Porcine complement was activated by treating sera with
      zymosan (PO ZYM) to generate C5b-9. C5b-9 binds to PAEC in a concentration- and
      time-dependent manner. PO ZYM-induced expression of ICAMs was maximally induced
      by 18h. Rapamycin reduced the expression of vascular cell adhesion molecule
      (VCAM) and P-selectin in a concentration-dependent manner. Adhesion of monocytes
      was reduced by rapamycin and the inhibition was prevented by antibodies to
      vascular cell adhesion molecule, P-selectin and endothelial-leukocyte adhesion
      molecule (ELAM). In summary, inhibition of the mammalian target of rapamycin down
      regulates complement-induced ICAMs expression which may modulate inflammatory
      responses that follow stent implant-induced restenosis during percutanous
      coronary interventions.

PMID- 16797890
TI  - Quality of life among postmenopausal Ecuadorian women participating in a
      metabolic syndrome screening program.
AB  - BACKGROUND: Quality of life decreases after the menopause as it has been assessed
      by several designed tools. Despite this, few studies have reported correlations
      between quality of life and the metabolic syndrome and its determinants.
      OBJECTIVE: Evaluate quality of life and determine factors related to its
      impairment among postmenopausal Ecuadorian women. METHODS: Postmenopausal women
      that participated in a metabolic syndrome screening and educational program at
      the Institute of Biomedicine of the Universidad Catolica of Guayaquil, Ecuador
      were interviewed using the Menopause-Specific Quality of Life Questionnaire
      (MENQOL). Mean domain scores as well as factors associated to higher scores
      within each of the domains of the questionnaire (vasomotor, psycho-social,
      physical and sexual) were determined. RESULTS: Three hundred twenty-five
      postmenopausal women (n=325) were surveyed. Mean age of participants was 55.9+/
      8.1 years (median: 54 years). Women presented metabolic syndrome, hypertension,
      hyperglycemia, hypertriglyceridemia and abdominal obesity in 41.5%, 38.8%, 16.6%,
      56.9% and 54.2% respectively. Mean scores obtained for each domain were:
      vasomotor: 3.5+/-2.5 (median 3); psycho-social: 3.7+/-1.5 (median 3.6); physical:
      3.8+/-1.2 (median 3.8); sexual: 4.9+/-2.3 (median 5.3). More than 50% of women
      had scores above the median for each domain of the questionnaire. Logistic
      regression determined that vasomotor score decreased with age. Abdominal obesity
      increased the risk of having vasomotor, psycho-social and physical scores above
      the median. Hypertension and hyperglycemia increased the risk for higher scores
      within the psycho-social and sexual domain respectively. CONCLUSION: In this
      postmenopausal Ecuadorian population, impairment of quality of life was found to
      be associated to age and related conditions such as abdominal obesity,
      hypertension and hyperglycemia.

PMID- 16797889
TI  - Comparison of chromaffin cells from several animal sources for their use as an in
      vitro model to study the mechanism of organophosphorous toxicity.
AB  - It had been observed that the chromaffin cells of bovine adrenal medulla contain
      high levels of neuropathy target esterase (NTE), the esterase whose inhibition
      and aging is associated with induction of the organophosphorous induced delayed
      neuropathy. In this study, total esterase and NTE activities, and their
      inhibition kinetics by OPs are characterized in adrenal medulla of several
      species in order to find the best source for chromaffin cells. Total esterase
      activity in membrane fraction of bovine, equine, porcine, ovine and caprine were
      6100+/-840, 4200+/-270, 5000+/-120, 28800+/-3000, and 10800+/-2400mU/gtissue,
      respectively (mean+/-S.D., n=3-4). NTE represented around 70%, 24%, 58%, 10% and
      24% of the total esterases in the same tissues, respectively. It was deduced that
      NTE represents between 69% and 89% of the "B-activity" (activity resistant to
      40microM paraoxon) in the membrane fraction of all species. The mipafox I(50)
      calculated for 30-min inhibition of NTE at 37 degrees Celsius ranged between 7.4
      and 12microM. These values are in the range of that for brain NTE in hen (the
      usual model for testing OP delayed neurotoxicity). Considering that bovine
      adrenal medulla contains high NTE activity, that it represents a high proportion
      of total activity, it is easier to dissect than adrenal medulla from equine,
      caprine or ovine, and is more readily available than species cited previously,
      and that its inhibitory properties are similar to the classical hen brain model,
      it is deduced that bovine adrenal medulla is the most appropriate source of
      chromaffin cells to study OP toxicity, with porcine as the second alternative.
      The kinetic properties of chromaffin cell cultures from bovine and porcine were
      in accordance with their properties in homogenate and subcellular fractions, and
      they displayed an appropriate stability and viability of the primary culture to
      be used in in vitro toxicological studies for both mechanistic and testing
      purposes.

PMID- 16797891
TI  - Attitudes towards the menopause and hormone therapy over the turn of the century.
AB  - OBJECTIVE: To assess attitudes and beliefs about the menopausal transition in a
      population of peri- and postmenopausal women, and if these attitudes differed
      before and after publication of studies on risks and benefits with hormone
      therapy (HT). MATERIALS AND METHODS: In 1999 and 2003 all women aged 53 and 54
      years in the community of Linkoping, Sweden, were sent a questionnaire about use
      of HT, menopausal status and attitudes regarding menopause and HT. RESULTS: Most
      women regarded menopause as a natural process characterized by both hormonal
      deficiency and aging and these views did not differ between 1999 and 2003. A
      majority of women thought that significant climacteric symptoms were a good
      reason to use HT, but not that women without symptoms should use HT. The fraction
      of women who supported HT use was, however, significantly lower in 2003 than in
      1999. Most women agreed that menopause leads to increased freedom and that it is
      a relief not to have to think about contraception and pregnancies. CONCLUSIONS:
      Most Swedish women had a mainly biological view on menopause but nevertheless
      they thought that only women with climacteric symptoms should use HT. Women's
      attitudes towards HT have changed after recent reports on risks from long-term
      use of HT whereas the attitudes towards the menopausal transition were stable.
      Other factors than attitudes towards menopause affect women's actual use of HT.
      Probably women's and health care provider's apprehension of the risk-benefit
      balance of HT use is one such factor.

PMID- 16797893
TI  - Physicochemical characterization and evaluation of a microemulsion system for
      antimicrobial activity of glycerol monolaurate.
AB  - The purpose of this study was to improve the depression, enhance the
      bioavailability, hence strengthen the antimicrobial ability of poorly water
      soluble glycerol monolaurate (GML) by loading it in microemulsion system.
      Microemulsions were prepared with GML as oil, tweens as surfactant, and medium
      and-short chain alcohols at different ratio as cosurfactants. The effect of the
      ratio of surfactant to cosurfactant on the stability of microemulsion was tested.
      And the effect of the composition and ratio of cosurfactant and the effect of
      potassium sorbate dissolved in water at different concentration on the area of
      O/W microemulsion region in pseudo-ternary phase diagrams were also investigated.
      The results showed that the microemulsion is most stable when the ratio of
      surfactant to cosurfactant was 3:2, the suitable cosurfactant is pentanol to
      dodecane at 2:1, the area of O/W microemulsion region in pseudo-ternary phase
      diagram increased with increasing content of potassium sorbate. The conclusion of
      this study was that GML loaded in microemulsion had much higher anti-microbial
      activity than GML alone.

PMID- 16797894
TI  - Information for gene networks in inner ear development: a study centered on the
      transcription factor gata2.
AB  - The search for molecular mechanisms to stimulate sensory regeneration in the
      mammalian inner ear is commonly based upon developmental studies. This has
      revealed many genes that regulate the differentiation of sensory cells. A major
      challenge is to place these genes into the context of functional networks that
      describe developmental processes more fully and increase the chances of
      identifying useful therapeutic targets. We used a novel approach to identify
      genes that are functionally related to the transcription factor gata2. Temporal
      profiles of gene expression were derived from three conditionally immortal cell
      lines and clustered to those of gata2 by applying the gamma model for
      oligonucleotide signals, a statistical method that allows quantitative analysis
      of oligonucleotide array data. We derived an objective list of 28 genes that
      clustered with gata2 in all three cell lines. A number of these genes have known
      functional links with gata2. Genes encoding CCAAT/enhancer binding proteins
      (C/EBP) and signal transducer and activation of transcription 3 (Stat3) are
      especially interesting as they are known to bind gata proteins directly. The
      results provide strong evidence that our experimental approach can reveal
      functional relationships between genes that regulate fundamental processes in the
      differentiation of sensory cells in the inner ear.

PMID- 16797892
TI  - The effects of surfactants on the dissolution profiles of poorly water-soluble
      acidic drugs.
AB  - The effects of types of surfactants on the solubilization and dissolution of
      poorly soluble acidic drugs were compared to identify the most suitable
      surfactant for conducting an acidic drug dissolution test. Cetyltrimethylammonium
      bromide (CTAB) as a cationic surfactant, sodium lauryl sulfate (SLS) as an
      anionic surfactant, and polysorbate 80 as a non-ionic surfactant were used in the
      study. And, mefenamic acid, nimesulide, and ibuprofen were selected as model
      drugs. The dissolution rates of these acidic drugs were substantially enhanced in
      medium containing CTAB. Electrostatic interactions between acidic drugs and
      cationic surfactants were confirmed by measuring UV spectra of each drug.
      Solubility of drugs in various media and the partition coefficients of drugs into
      micelles were found to depend on drug characteristics. For acidic drugs, the
      ability of media containing a cationic surfactant to discriminate rates of
      dissolution of acidic drugs seemed to be greater than that of media containing
      other surfactant types.

PMID- 16797895
TI  - The effect of center frequency and bandwidth on the auditory evoked magnetic
      field.
AB  - Auditory evoked magnetic fields in relation to the center frequency of sound with
      a certain bandwidth were examined by magnetoencephalography (MEG). Octave band,
      1/3 octave band, and 130 Hz bandwidth noises were used as the sound stimuli. All
      signals were presented at 60 dB SPL. The stimulus duration was 500 ms, with rise
      and fall ramps of 10 ms. Ten normal-hearing subjects took part in the study.
      Auditory evoked fields were recorded using a 122 channel whole-head magnetometer
      in a magnetically shielded room. The latencies, source strengths and coordinates
      of the N1m wave, which was found above the left and right temporal lobes around
      100 ms after the stimulus onset, were analyzed. The results demonstrated that the
      middle frequency range had shorter N1m latencies and larger N1m amplitudes, and
      that the lower and higher frequency stimuli had relatively delayed N1m latencies
      and decreased N1m amplitudes. The N1m amplitudes correlated well to the loudness
      values in the frequency ranges between 250 and 2000 Hz. The source locations of
      N1m did not reveal any systematic changes related to the center frequency and
      bandwidth.

PMID- 16797896
TI  - Acoustic model investigation of a multiple carrier frequency algorithm for
      encoding fine frequency structure: implications for cochlear implants.
AB  - Current cochlear implants provide frequency resolution through the number of
      channels. Improving resolution by increasing channels is limited by factors such
      as the physiological feasibility of increasing the number of electrodes, the
      inability to increase the number of channels for those already implanted, and the
      increased possibility of channel interactions reducing channel efficacy. Recent
      studies have suggested an alternative method: providing a continuum of pitch
      percepts for each channel based on the frequency content of that channel. This
      study seeks to determine the frequency resolution necessary for the highest
      performance gain, which may give some indication of the feasibility for
      implementation in implants. A discrete set of carrier frequencies, instead of a
      continuum, are evaluated using an acoustic model to measure speech recognition.
      Performance increased as the number of available frequencies increased, and
      substantive improvement was seen with as few as two frequencies per channel. The
      effect of variable frequency discrimination was also assessed, and the results
      suggest that frequency modulation can still provide benefits with poor frequency
      discrimination on some channels. These results suggest that if two or more
      discriminable frequencies per channel can be generated for cochlear implant
      subjects then an improvement in speech recognition may be possible.

PMID- 16797897
TI  - Altered expression of serum protein in ginsenoside Re-treated diabetic rats
      detected by SELDI-TOF MS.
AB  - Diabetes mellitus (DM) is now a global health problem, however, its pathogenesis
      has not yet been fully deciphered. Even though modern medicine has great
      contribution to the control and treatment of DM, it is still far from success to
      completely cure the disease. Panax ginseng C.A. Meyer (ginseng) is a well
      recognized traditional Chinese medicine for treating DM in Asia. In this study,
      high throughput proteomic approach has been adopted to investigate the
      antidiabetic action of 2 weeks' ginsenoside Re (Re, a major component of ginseng)
      administration to streptozotocin-induced diabetic rats. Employing surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF
      MS) and bioinformatics, 432 cluster peaks were detected in the samples, among
      them 293 potential biomarkers were found to have significant differentiations
      between the DM and control normal rats. When the Re-treated diabetic rats were
      compared to the untreated ones, a protein peak was detected to have significant
      alteration corresponding to Re treatment. This specific protein was found to
      match with C-reactive protein (CRP) in the protein database, and was subsequently
      validated by ELISA. This is the first study demonstrated that CRP could be
      altered by Re treatment, indicating that Re may improve diabetes and its
      complications by alleviation of inflammation.

PMID- 16797898
TI  - Protective effect of Lygodium flexuosum (L.) Sw. (Lygodiaceae) against D
      galactosamine induced liver injury in rats.
AB  - The protective effect of Lygodium flexuosum n-hexane extract against D
      galactosamine was evaluated in Wistar rats. In preventive groups extract was
      administered at 48, 24 and 2h before D-galactosamine intoxication whereas in post
      treatment groups extract were administered 2, 24 and 48 h after D-galactosamine
      intoxication. Rats pre-treated with n-hexane extract at a dose of 200 and 100
      mg/kg of Lygodium flexuosum showed a significant prevention of elevated AST, ALT,
      LDH levels and hepatic malondialdehyde in D-galactosamine treated rats. Hepatic
      glutathione levels significantly upregulated by the extract treatment in D
      galactosamine treated rats. Quantification of histopathological sections
      supported the preventive action of n-hexane extract of Lygodium flexuosum. Rats
      treated with the extract at a dose of 200 and 100 mg/kg Lygodium flexuosum after
      the establishment of D-galactosamine induced liver injury showed complete
      protection of liver as evidenced from normal AST, ALT and LDH levels, hepatic GSH
      and MDA levels and also by normal histological index of liver in treated rats.
      Rats treated with n-hexane extract of Lygodium flexuosum were comparable to that
      of Silymarin, the standard hepatoprotective drug.

PMID- 16797899
TI  - Protective effect of tanshinone IIA on human umbilical vein endothelial cell
      injured by hydrogen peroxide and its mechanism.
AB  - Tanshinone IIA (Tan IIA) is isolated from Salvia miltiorrhiza, the root of which
      is widely used as a traditional Chinese medicine to treat atherosclerosis. The
      aim of the present study was to evaluate the putative protective effect of Tan
      IIA in a human umbilical vein endothelial cell line (ECV-304) injured by hydrogen
      peroxide in vitro and the mechanism of its protection. The percentage of cell
      viability was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl
      tetrazolium bromide (MTT) assay. The endothelial cell apoptosis and expression of
      cluster of differentiation 40 (CD40) were detected by flow cytometric analysis.
      Preincubation with Tan IIA significantly increased the viability of ECV-304 cell
      injured by hydrogen peroxide, which was accompanied with the increased nitric
      oxide level and superoxide dismutase activity in a dose-dependent manner.
      Moreover, cell apoptosis and CD40 expression were decreased in a dose-dependent
      manner. In conclusion, our data suggests that Tan IIA protects ECV-304 cell
      damage induced by hydrogen peroxide through its anti-oxidant effect and CD40 anti
      inflammatory approach.

PMID- 16797900
TI  - Tasks of research in forensic medicine - different study types in clinical
      research and forensic medicine.
AB  - In the last years the research output of forensic medicine has sometimes been
      regarded as insufficient and as of poor quality, especially when parameters as
      impact factors and external funding were taken into account. However, forensic
      medicine has different tasks compared to clinical medicine. The main difference
      between basic subjects, clinical and forensic medicine is not a lack of
      scientific efficiency in forensic medicine but is a result of the questions
      asked, the available methods and specific aims. In contrast to natural-scientific
      research, forensic science has furthermore important intersections with arts and
      socio-scientific disciplines. Etiologic and pathogenetic research is of only
      limited relevance in forensic medicine. Thus, forensic medicine is excluded from
      these research fields, which are mainly supported by external funding. In
      forensic medicine research mainly means applied research regarding findings, the
      probative value and reconstruction as well as examination at different points of
      intersection between medicine and law. Clinical types of research such as
      controlled randomised, prospective cross-sectional, cohort or case-control
      studies can only rarely be applied in forensic medicine due to the area specific
      research fields (e.g. thantatology, violent death, vitality, traffic medicine,
      analytical toxicology, hemogenetics and stain analysis). The types of studies
      which are successfully established in forensic medicine are comparison of
      methods, sensitivity studies, validation of methods, kinetic examinations etc.
      Tasks of research in forensic medicine and study types, which may be applied will
      be addressed.

PMID- 16797901
TI  - Estimation of the time since death.
AB  - The main principle of the determination of the time since death is the
      calculation of a measurable date along a time-dependent curve back to the start
      point. Characteristics of the curve (e.g. the slope) and the start point are
      influenced by internal and external, antemortem and postmortem conditions. These
      influencing factors have to be taken into consideration quantitatively in order
      to improve the precision of death time estimation. It does not make any sense to
      study the postmortem time course of any analyte without considering influencing
      factors and giving statistical parameters of the variability. Comparison of
      different methods requires an investigation of the same postmortem interval. For
      practical purposes, it must be concluded that the amount of literature on
      estimating the time since death has a reverse correlation with its importance in
      practice.

PMID- 16797902
TI  - Topiramate in children with autistic spectrum disorders.

PMID- 16797903
TI  - Effects of vitamin D supplementation and exercise training on physical
      performance in Chilean vitamin D deficient elderly subjects.
AB  - The aim was to assess the effects of resistance training and vitamin D
      supplementation on physical performance of healthy elderly subjects. Ninety-six
      subjects, aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less,
      were randomized to a resistance training or control group. Trained and control
      groups were further randomized to receive in a double blind fashion, vitamin D
      400 IU plus 800 mg of calcium per day or calcium alone. Subjects were followed
      for nine months. Serum 25 OH vitamin D increased from 12.4+/-2.2 to 25.8+/-6.5
      ng/ml among subjects supplemented with vitamin D. Trained subjects had
      significant improvements in quadriceps muscle strength, the short physical
      performance test and timed up and go. The latter improved more in trained
      subjects supplemented with vitamin D. At the end of the follow up, gait speed was
      higher among subjects supplemented with vitamin (whether trained or not) than in
      non-supplemented subjects (838+/-147 and 768+/-127 m/12 min, respectively,
      p=0.02). Romberg ratio was lower among supplemented controls than non
      supplemented trained subjects (128+/-40% and 144+/-37%, respectively, p=0.05). In
      conclusion, vitamin D supplementation improved gait speed and body sway, and
      training improved muscle strength.

PMID- 16797905
TI  - IL-6 promoter polymorphisms and quantitative traits related to the metabolic
      syndrome in KORA S4.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine which has been proposed as
      "cytokine for gerontologists" and linked to age-related metabolic disturbances
      such as the metabolic syndrome or type 2 diabetes. Polymorphisms located in the
      promoter region of IL-6 have been reported to be involved in the regulation of IL
      6 transcription. This study investigates whether IL-6 promoter variants -174 G/C
      and -573 G/C are associated with quantitative traits related to the metabolic
      syndrome (International Diabetes Federation criteria) in a population of
      normoglycemic subjects (n=878) from the latest KORA survey (KORA S4). Genotyping
      was performed using MALDI-TOF MS. Besides lower height (p=0.01) the -174 CC
      genotype was independently associated with lower waist (p=0.002) and hip (p=0.01)
      circumferences in men. Furthermore, the -174 CC genotype was associated with BMI
      (p=0.004) when adjusted for waist and hip circumference. The present study does
      not suggest associations with further components of the metabolic syndrome. The
      association with height seems to be the central factor indicating an influence of
      IL-6 on growth through impaired bone metabolism. However, the complex
      relationships need further investigation.

PMID- 16797904
TI  - A comparison of elderly and adult multiple organ dysfunction syndrome in the rat
      model.
AB  - Multiple organ dysfunction syndrome (MODS) in the elderly is the most common
      cause of mortality in critically ill elderly patients, and it is different from
      MODS in the adult in clinic. Rare studies have been done on its pathogenesis and
      the comparison between adult and elderly MODS animal models. This work aimed at
      exploring the mechanisms mediating elderly MODS and compared this with adult
      MODS. Male Sprague-Dawley aged and adult rats were intraperitoneally injected
      with zymosan for incitement of MODS. Aged rats receiving zymosan showed severer
      pulmonary, cardiac and renal dysfunctions than adult rats. Likewise, the tissue
      lesions under light microscope in major organs of zymosan treated aged rats were
      much worse than those of zymosan treated adult rats. Moreover, zymosan treated
      aged rats showed 142% and 64% greater increase in pulmonary alveolar macrophages
      (AMs) apoptotic rate and serum TNF-alpha level, respectively, whereas 43% smaller
      increase in serum IL-10 level compared to zymosan treated adult rats.
      Furthermore, lung injury was much worse than that in other organs in zymosan
      treated aged rats. Overall, these results suggest that zymosan can be used in
      aged rats to incite MODS in the elderly. In the animal model of elderly MODS,
      there are (1) severer injury in lung, heart and kidney vs adult; (2) easier to
      develop severe systemic inflammatory response syndrome (SIRS) instead of
      compensatory anti-inflammatory response syndrome (CARS) compared to the adult;
      and (3) severer inflammation in lung than other organs indicative of the possible
      roles of lung in triggering MODS in the elderly.

PMID- 16797906
TI  - MDCT in blunt intestinal trauma.
AB  - Injuries to the small and large intestine from blunt trauma represent a defined
      clinical entity, often not easy to correctly diagnose in emergency but extremely
      important for the therapeutic assessment of patients. This article summarizes the
      MDCT spectrum of findings in intestinal blunt lesions, from functional disorders
      to hemorrhage and perforation.

PMID- 16797907
TI  - Volatilisation of metals and metalloids by the microbial population of an
      alluvial soil.
AB  - In order to assess the microbial contribution to the volatilisation of
      metal(loid)s by methylation and hydridisation in the environment, we focused on
      soils of different origin. Here, we describe the biogenic production of volatile
      metal(loid) species of an alluvial soil with rather low metal(loid)
      contamination. The production of volatile metal(loid) compounds was monitored in
      soil suspensions kept under anaerobic conditions over an incubation time of 3
      months. In the headspace of the samples, we detected mainly hydrids and
      methylated derivatives of a broad variety of elements such as arsenic, antimony,
      bismuth, selenium, tellurium, mercury, tin and lead, with the volatile products
      of arsenic, antimony and selenium representing the highest portions. Classical
      cultivation-dependent procedures resulted in the isolation of a strictly
      anaerobic Gram-positive strain (ASI-1), which shows a high versatility in
      transforming metal(loid) ions to volatile derivatives. Strain ASI-1 is affiliated
      to the species Clostridium glycolicum due to its high 16S rDNA sequence
      similarity with members of that species. As shown by fluorescence in situ
      hybridisation, strain ASI-1 amounts to approximately 2% of the total microbial
      flora of the alluvial soil. Since the spectrum of volatile metal(loid) compounds
      produced by this strain is very similar to that obtained by the whole population
      regarding both the broad variety of metal(loid)s converted and the preference for
      volatilising arsenic, antimony and selenium, we suggest that this strain may
      represent a dominant member of the metal(loid) volatilisating population in this
      habitat.

PMID- 16797908
TI  - Augmentation of near infrared diffuse reflectance and transmittance spectral data
      for the development of robust PLSBC models for classifying double blind clinical
      trial tablets.
AB  - The water content of clinical trial tablets can be different between and within
      different tablet batches, depending on the relative humidity conditions during
      their production, packaging, storage and analysis. These water variations lead to
      important spectral variations in the near infrared spectral region which can lead
      to a wrong identification if the classification model was based on
      unrepresentative data towards the water content. As model development for
      clinical trial studies needs to be extremely fast - within one working day - with
      generally only one batch available, the principle of data augmentation has to be
      applied to render more robust classification models. Therefore, tablets available
      for constructing the model are being processed in order to increase or decrease
      their water content and to make them more representative for tablets to be tested
      in the future. The inclusion of a deliberate water variation is the most
      efficient way to develop a model, for which no additional model redevelopment
      will be required to pass the system suitability tests and to obtain a correct
      identification.

PMID- 16797909
TI  - Integration of a rapid automated solubility classification into early validation
      of hits obtained by high throughput screening.
AB  - Besides the structural verification of hits generated by high throughput
      screening also the determination of physicochemical properties is essential for
      an efficient lead identification. Especially solubility is fundamental for the
      correct planning and interpretation of experiments. We describe the set up of a
      fast automated solubility test within our existing workflow for hit validation to
      assure compound identity and purity. 384-Well plates with hit validation compound
      solution are used for analysis employing liquid chromatography and mass
      spectrometry (LC/MS). The remaining compound solution was used for a fast
      automated solubility classification employing a nephelometer integrated into a
      Tecan robotic workstation. Thereby 9000 compounds were classified as poorly- and
      well-soluble. This rapid and simple test does not require any additional amount
      of sample or sample processing than before but provides additional information on
      the hits at an early stage of lead identification. Validated by a more detailed
      nephelometric analysis for 500 out of the 9000 compounds in different buffer
      systems this simple test has shown to produce relevant data.

PMID- 16797910
TI  - Application of monolithic column in quantification of gliclazide in human plasma
      by liquid chromatography.
AB  - A simple, rapid and sensitive isocratic reversed phase HPLC method with UV
      detection using a monolithic column has been developed and validated for the
      determination of gliclazide in human plasma. The assay enables the measurement of
      gliclazide for therapeutic drug monitoring with a minimum quantification limit of
      10ngml(-1). The method involves simple, one-step extraction procedure and
      analytical recovery was complete. The separation was carried out in reversed
      phase conditions using a Chromolith Performance (RP-18e, 100mmx4.6mm) column with
      an isocratic mobile phase consisting of 0.01M disodium hydrogen phosphate buffer
      acetonitrile (52:48, v/v) adjusted to pH 4.0. The wavelength was set at 230nm.
      The calibration curve was linear over the concentration range 10-5000ngml(-1).
      The coefficients of variation for inter-day and intra-day assay were found to be
      less than 6.0%.

PMID- 16797911
TI  - Dissolution test for lamivudine tablets: optimization and statistical analysis.
AB  - A comparison of different methods for dissolution test used by five different
      manufacturer laboratories of lamivudine tablets is made, evaluated, and
      discussed. Dissolution medium (water and hydrochloric acid pH 1.2), apparatus
      (paddles and baskets) and time (30 and 60 min) were analyzed. The determination
      was accomplished by spectrophotometry at 270 nm. Analysis of variance (ANOVA)
      factorial design 5 x 2 x 2 x 2 with six repetitions, with post hoc multiple
      comparisons between means conducted by Duncan test at 0.05 significance level was
      used. After the comparative analysis of the results, optimal dissolution
      conditions were determined as follows: water as dissolution medium, paddles at
      the stirring speed of 50 rpm as apparatus and time of 30 min. The method was
      applied to the dissolution test of samples from eleven batches of tablets,
      produced by five different laboratories.

PMID- 16797912
TI  - Relationships between thyroid status, tissue oxidative metabolism, and muscle
      differentiation in bovine fetuses.
AB  - The temporal relationships between thyroid status and differentiation of liver,
      heart and different skeletal muscles were examined in 42 bovine fetuses from day
      110 to day 260 of development using principal component analysis of the data.
      Plasma concentrations of reverse-triiodothyronine (rT(3)) and thyroxine (T(4))
      increased during development from day 110 to day 210 or 260, respectively,
      whereas concentration of triiodothyronine (T(3)) and hepatic type-1 5'-deiodinase
      activity (5'D1) increased from day 180 onwards. On day 260, high T(4) and rT(3)
      and low T(3) concentrations were observed together with a mature 5'D1 activity.
      Cytochrome-c oxidase (COX) activity expressed per mg protein increased at day 180
      in masseter and near birth in masseter, rectus abdominis and cutaneus trunci
      muscles (P<0.05). Significant changes in citrate synthase (CS) activity per mg
      protein were observed between day 110 and day 180 in the liver and between day
      210 and day 260 in the liver, the heart and the longissimus thoracis muscle
      (P<0.05). Muscle contractile differentiation was shown by the disappearance of
      the fetal myosin heavy chain from day 180 onwards. A positive correlation
      (r>0.47, P<0.01) was shown between thyroid status parameters (5'D1,
      concentrations of T(4) and T(3)) and COX activity in muscles known to be
      oxidative after birth (masseter, rectus abdominis) but not in liver and heart,
      nor in muscles known to be glycolytic after birth (cutaneus trunci, longissimus
      thoracis). A similar correlation was found between thyroid parameters and CS
      activity in liver and masseter. Results indicate that elevation of plasma T(3)
      concentrations in the last gestational trimester could be involved in the
      differentiation of oxidative skeletal muscles.

PMID- 16797913
TI  - Effects of gestation and lactation on vitamin D receptor amounts in goats and
      sheep.
AB  - During gestation and lactation, an increased demand for calcium (Ca) due to the
      development of fetal skeleton and excretion via milk is observed. The higher need
      for Ca is met by an augmented mobilisation of Ca from bones and by an increased
      absorption from the intestines. The main influence on this physiological process
      of active absorption has Vitamin D, acting through Vitamin D receptors (VDR)
      located in the mucosal wall of the intestines, thus increasing Ca absorption. As
      a consequence of inadequate Ca absorption, metabolic diseases like milk fever can
      develop. In this study immunohistochemical procedures were applied to colon
      mucosa biopsies of pregnant and lactating goats and sheep, to study the effect of
      late gestation, parturition and lactation on VDR amount. Colon mucosa biopsies
      were collected 2 weeks before parturition, 1 and 4 weeks post partum (pp), 2, 3,
      4, and 5 months pp from 11 dairy goats and 11 sheep. Immunohistochemistry was
      performed employing a biotinylated monoclonal rat anti-VDR antibody and
      streptavidin peroxidase techniques. Nuclei and cytoplasm of enterocytes stained
      positively for VDRs. Strongest immunoreactions were observed in intermediate and
      superficial glandular cells. The biopsy samples taken during early lactation
      revealed a lower immunoreaction for VDR compared with samples taken during later
      stages of lactation. In conclusion, immunochemistry and biopsy technology are
      useful tools to assess changes in VDR expression in relation to varying demands
      for Ca in the process of a reproductive cycle. These results show that in dairy
      goats and sheep, an influence of gestation and lactation on VDR is obvious.

PMID- 16797914
TI  - The effect of the myotoxic Lys49 phospholipase A(2) from Agkistrodon contortrix
      laticinctus snake venom on Na+/K+ -ATPase activity of toad bladders.
AB  - ACLMT is a myotoxic Lys49 phospholipase A(2) isolated from the venom of the snake
      Agkistrodon contortrix laticinctus. We have previously shown that ACLMT increases
      baseline water transport and partially inhibits vasopressin-stimulated water
      transport across toad bladders due to an increase in cytosolic calcium. However,
      these evidences provide insufficient insight into the mechanisms involved in the
      effects of ACLMT on membrane permeability. In an attempt to better understand
      such mechanisms, the current study aimed to investigate whether the Na(+)/K(+)
      ATPase activity of isolated toad bladders can be affected by the ACLMT and the
      synthetic peptide from its C-terminal region. The toxin significantly decreased
      the Na(+)/K(+)-ATPase, while the peptide did not alter it. These findings suggest
      that the effects of ACLMT on membrane permeability may be due to the inhibition
      of the Na(+)/K(+)-ATPase activity, and that the C-terminal region may not play a
      relevant role in this effect. This study contributes toward a better
      understanding of the mechanisms involved in the toxicity of the snake venom Lys49
      PLA(2) myotoxins on biological tissues.

PMID- 16797915
TI  - Flow cytometric cell cycle analysis allows for rapid screening of estrogenicity
      in MCF-7 breast cancer cells.
AB  - The quantitative measurement of individual cells and their characteristics by
      means of flow cytometry is already for many years of great value for clinical
      studies. However, its potential as a tool in (eco)toxicology has only recently
      been discovered. Analysis of cell cycle kinetics with DNA-staining dyes can offer
      a valuable alternative to detect effects of chemicals on cell proliferation, an
      important endpoint in screening estrogen-like properties of chemicals. In the
      present study, flow cytometric cell cycle analysis in growth arrested MCF-7 cells
      exposed to five xenoestrogens correspond well with cell proliferation results of
      the conventionally used E-screen assay. Moreover, re-induction of proliferation
      in MCF-7 cells, indicated by the percentage of cells in S(ynthesis)-phase, is
      most pronounced after 24 h exposure, thus allowing a faster screening of
      xenoestrogens. This flow cytometric proliferation assay confirms that the
      estrogenic activity of structurally analogous parabens is mediated by the
      estrogen receptor pathway and is proportional to the alkyl chain length.
      Moreover, the ER-mediated mode of action of two fluorotelomer alcohols (6:2 FTOH
      and 8:2 FTOH), recently reported as xenoestrogenic, could be elucidated. These
      results support the potential of flow cytometric cell cycle kinetics as a
      screening assay for estrogen-like properties of chemicals.

PMID- 16797916
TI  - Misdiagnosis of the persistent postconcussion syndrome in patients with
      depression.
AB  - The purpose of this study is to examine the prevalence of postconcussion-like
      symptoms in patients with depression. Participants were 64 physician-diagnosed
      inpatients or outpatients with depression who had independently-confirmed
      diagnoses on the Structured Clinical Interview for DSM-IV. All completed the
      British Columbia Postconcussion Symptom Inventory, a 16-item measure designed to
      assess the frequency and severity of symptoms based on ICD-10 criteria for
      postconcussion syndrome. Specific endorsement rates of postconcussion-like
      symptoms ranged from 31.2% to 85.6% for symptoms rated mild or greater, and from
      10.9% to 57.8% for symptoms rated moderate-to-severe. Approximately 9 out of 10
      patients with depression met liberal self-report criteria for a postconcussion
      syndrome and more than 5 out of 10 met conservative criteria for the diagnosis.
      Implications for forensic neuropsychology will be discussed.

PMID- 16797918
TI  - Awaking and sleeping of a complex network.
AB  - A network with a logistic-like local dynamics is considered. We implement a mean
      field multiplicative coupling among first-neighbor nodes. When the coupling
      parameter is small, the dynamics is dissipated and there is no activity: the
      network is turned off. For a critical value of the coupling, a non-null stable
      synchronized state, which represents a turned on network, emerges. This global
      bifurcation is independent of the network topology. We characterize the
      bistability of the system by studying how to perform the transition, which is now
      topology dependent, from the active state to that with no activity, for the
      particular case of a scale-free network. This could be a naive model for the
      wakening and sleeping of a brain-like system, i.e., a multi-component system with
      two different dynamical behaviors.

PMID- 16797917
TI  - Inherited and acquired thrombophilia: pregnancy outcome and treatment.
AB  - Maternal thrombophilias increases the risk of an adverse pregnancy outcome. An
      extensive literature review highlights the role of inherited and acquired
      thrombophilic disorders in spontaneous abortion, both early and late, recurrent
      or isolate, in intrauterine growth retardation, in placenta abruption, in pre
      eclampsia and in venous thromboembolism. We have particularly focused attention
      on the following factors: antithrombin III (ATIII), proteins C (PC) and S (PS)
      deficiencies, genetic mutations particularly factor V Leiden (FVL), prothrombin
      gene G20210A (PTM) and the thermolabile variant of the methylene tetrahydrofolate
      reductase C677T (MTHFR) gene, lupus anticoagulant (LAC) and anticardiolipin
      antibodies, VIIIc factor, hyperhomocysteinemia and acquired activated protein C
      resistance. Appropriate treatment can improve pregnancy outcome without
      teratogenic effects.

PMID- 16797919
TI  - A descriptive method to evaluate the number of regimes in a switching
      autoregressive model.
AB  - This paper proposes a descriptive method for an open problem in time series
      analysis: determining the number of regimes in a switching autoregressive model.
      We will translate this problem into a classification one and define a criterion
      for hierarchically clustering different model fittings. Finally, the method will
      be tested on simulated examples and real-life data.

PMID- 16797920
TI  - Speed-accuracy trade-off in planned arm movements with delayed feedback.
AB  - The Vector Integration to Endpoint (VITE) circuit describes a real-time neural
      network model simulating behavioral and neurobiological properties of planned arm
      and hand movements by the interaction of two populations of neurons. We analyze
      the speed-accuracy trade-off generated by this circuit, generalized to include
      delayed feedback. With delay, two important new properties of the circuit emerge:
      a breakdown of Fitts' law when the movement time is small relative to the delay;
      and a positive Fitts' law Y-intercept. This breakdown of Fitts' law for tasks
      with small Index of Difficulty has been previously observed experimentally, and
      we suggest it may be attributed at least in part to delay effects in the nervous
      system elaborated by the model. Additionally, this gives a theoretical
      explanation for why positive Fitts' law Y-intercept should occur, and that it is
      related to the delay within the movement circuit.

PMID- 16797921
TI  - Graph-based normalization and whitening for non-linear data analysis.
AB  - In this paper we construct a graph-based normalization algorithm for non-linear
      data analysis. The principle of this algorithm is to get a spherical average
      neighborhood with unit radius. First we present a class of global dispersion
      measures used for "global normalization"; we then adapt these measures using a
      weighted graph to build a local normalization called "graph-based" normalization.
      Then we give details of the graph-based normalization algorithm and illustrate
      some results. In the second part we present a graph-based whitening algorithm
      built by analogy between the "global" and the "local" problem.

PMID- 16797923
TI  - Classification of adolescent psychotic disorders using linear discriminant
      analysis.
AB  - BACKGROUND: The differential diagnosis between schizophrenia and bipolar disorder
      during adolescence presents a major clinical problem. Can these two diagnoses be
      differentiated objectively early in the courses of illness? METHODS: We used
      linear discrimination analysis (LDA) to classify 28 adolescent subjects into one
      of three diagnostic categories (healthy, N=8; schizophrenia, N=10; bipolar, N=10)
      using subsets from a pool of 45 variables as potential predictors (22
      neuropsychological test scores and 23 quantitative structural brain
      measurements). The predictor variables were adjusted for age, gender, race, and
      psychotropic medication. All possible subsets composed of k=2-12 variables, from
      the set of 45 variables available, were evaluated using the robust leaving-one
      subject-out method. RESULTS: The highest correct classification (96%) of the 3
      diagnostic categories was yielded by 9 sets of k=12 predictors, comprising both
      neuropsychological and brain structural measures. Although each one of these sets
      misclassified one case, each set correctly classified (100%) at least one group,
      such that a fully correct diagnosis could be reached by a tree-type decision
      procedure. CONCLUSIONS: We conclude that LDA with 12 predictor variables can
      provide correct and robust classification of subjects into the three diagnostic
      categories above. This robust classification relies upon both neuropsychological
      and brain structural information. Our results demonstrate that, despite
      overlapping clinical symptoms, schizophrenia and bipolar disorder can be
      differentiated early in the course of disease. This finding has two important
      implications. Firstly, schizophrenia and bipolar disorder are different
      illnesses. If schizophrenia and bipolar are dissimilar clinical manifestations of
      the same disease, we would not be able to use non-clinical information to
      classify ('diagnose') schizophrenia and bipolar disorder. Secondly, if this
      study's findings are replicated, brain structure (MRI) and brain function
      (neuropsychological) used together may be useful in the diagnosis of new
      patients.

PMID- 16797924
TI  - Mixed handedness is associated with the Disorganization dimension of schizotypy
      in a young male population.
AB  - Within the ASPIS (Athens Study of Psychosis Proneness and Incidence of
      Schizophrenia) we sought out to examine in accordance with previous reports if a
      deviation from dextrality is associated with an augmented endorsement of self
      rated schizotypal personality traits in a large population of 1129 young male
      army recruits. Schizotypal traits were assessed using the Schizotypal Personality
      Questionnaire and hand preference membership was determined by applying stringent
      criteria derived from the Annett Handedness Questionnaire and the Porac-Coren
      questionnaire of lateral preferences. By adopting three different definitions of
      hand preference membership, we confirmed an association between mixed handedness
      and increased schizotypal personality traits, and in particular with
      Disorganization schizotypy that encompasses aspects of self perceived
      difficulties in verbal communication. Non-verbal cognitive ability, as indexed by
      measurement of non-verbal IQ, sustained attention and working memory was not
      associated with hand preference. We argue that a deviation from normal cerebral
      lateralization, as indexed by mixed handedness, is associated with mild sub
      clinical language dysfunction, rather than non-verbal cognitive ability, and this
      might be relevant to the expression of psychosis phenotype.

PMID- 16797925
TI  - Evidence of altered neurogranin immunoreactivity in areas 9 and 32 of
      schizophrenic prefrontal cortex.
AB  - Schizophrenia is a complex and poorly understood neuropsychiatric disorder. Much
      research has begun to implicate the prefrontal cortex in the disease. Using
      immunocytochemistry we determined if neurogranin, a protein found in dendrites,
      spines and cell bodies and an upstream regulator of calcium was altered in areas
      9 and 32 of schizophrenic prefrontal cortex. We examined its expression in
      pyramidal cells in layers III and V. Tissues from 7 controls and 7 schizophrenics
      (from our original MAP2 study, Jones, L., Johnson, N., Byne, W., 2002.
      Alterations in MAP2 staining in area 9 and 32 of schizophrenic prefrontal cortex.
      Psych. Res. 114, 137-148) matched for age, sex and postmortem interval were
      examined. Using area fraction analysis we quantified the immunostaining.
      Additionally, we counted the number of positively stained pyramidal cells in the
      same 7 pairs. Neurogranin immunostaining was dramatically reduced in both layers
      III (72%) and V (50%) in area 9. In area 32 there was a more modest reduction in
      both layers III (36%) and V (40%). There was no difference in either brain region
      or layer in the density of positively stained pyramidal cells. These data confirm
      mounting evidence suggesting dendritic loss in the prefrontal cortex and suggest
      that the loss of protein does not appear to be due to a change in the number of
      cells producing the protein but rather in the amount of protein being produced.
      Additionally, these data suggest that the loss of neurogranin may alter the
      calcium-calmodulin dependent pathways due to its role as a regulator of
      calmodulin suggesting a link between structural and functional alterations of the
      pyramidal cells in the prefrontal cortex.

PMID- 16797926
TI  - Extracorporeal photopheresis: a focus on apoptosis and cytokines.
AB  - Induction of apoptosis and changes to cytokine secretion patterns have been
      implicated in the mechanism of action of extracorporeal photopheresis (ECP).
      Lymphocyte apoptosis is initially detected in significant numbers prior to re
      infusion and by 48 h post-ECP the majority of treated lymphocytes are apoptotic.
      The early apoptosis involves changes to mitochondrial function, reversal of the
      Bcl-2/Bax ratio and externalisation of phosphatidylserine. Apoptotic lymphocytes,
      observed from 20 h post-ECP, are associated with enhanced levels of CD95 and Fas
      ligand. For cutaneous T cell lymphoma (CTCL), processing of the apoptotic
      lymphocytes, by suitable antigen presenting cells (APCs), is suggested to induce
      a clonal cytotoxic response which targets the malignant T cell population.
      Increased levels of TNFalpha and IFNgamma, observed post-ECP in monocytes and
      lymphocytes, respectively, are thought to further contribute to the proposed anti
      tumour reaction seen in CTCL. However, down-regulation of pro-inflammatory
      cytokines and enhanced anti-inflammatory responses have been reported following
      ECP treatment. These immune responses may contribute to the tempering of the
      inflammatory conditions, such as graft versus host disease, which respond to ECP.
      Furthermore, untreated monocytes exposed to ECP-treated lymphocytes have also
      demonstrated a shift in monocyte cytokine-secretory pattern, toward one
      associated with immune tolerance. Recently, a mechanism of ECP-induced immune
      tolerance has been linked to the stimulation of the anti-inflammatory cytokines
      IL10 and TGFbeta by T regulatory cells, following the infusion of ECP-treated
      CD11c(+) APCs. Ultimately, the multifaceted responses, induced by ECP, may
      explain the diversity of clinical conditions that benefit.

PMID- 16797927
TI  - Verifiable single nucleotide polymorphisms of the internal transcribed spacer 2
      region for the identification of 11 Malassezia species.

PMID- 16797928
TI  - Characterization of a two-gene operon epeRA involved in multidrug resistance in
      Streptomyces clavuligerus.
AB  - Two genes, epeR and epeA, are located downstream of argH in the Streptomyces
      clavuligerus genome. EpeR belongs to the TetR family of transcriptional
      regulators. It is homologous to PqrA of Streptomyces coelicolor (74.3% identity)
      and to NfxB of Pseudomonas aeruginosa (30.9% identity). EpeA encodes a protein
      with 14 transmembrane spanning domains (TMS) of the major facilitator
      superfamily. It shares 68.9% identity to PqrB of S. coelicolor and 46.5% identity
      to LfrA, conferring resistance to fluoroquinolones in Mycobacterium smegmatis.
      Disruption of epeR results in a S. clavuligerus epeR::aph mutant which shows
      increased resistance to ethidium bromide and proflavine (16- and 32-fold higher
      than the wild type). Taking into consideration the sensitivity to drugs of
      different transformants carrying functional copies of either epeR or epeA, it
      might be concluded that both genes appear to be co-transcribed, with epeR
      encoding a regulatory protein which controls the expression of epeA.

PMID- 16797929
TI  - Construction of transposition insertion libraries and specific gene inactivation
      in the pathogen Lactococcus garvieae.
AB  - This paper reports the development of genetic tools in Lactococcus garvieae, an
      important Gram-positive bacterial pathogen affecting both fish and mammals. The
      vector pGKV210, a broad host range vector, was introduced by electroporation into
      L. garvieae UNIUD074. The maximal frequency obtained was 3.2 x 10(5)
      transformants/mug of DNA. Moreover, this effect is highly reproducible and
      appears to be constant, since all L. garvieae strains tested were transformed.
      Once the optimal transformation procedure was established, it was used to
      generate isogenic and transposition mutants. Insertional mutagenesis of the L.
      garvieae SA9H10L gene, similar to a Streptococcus pyogenes gene encoding the M
      protein (emm64), was carried out using the conditional replication plasmid
      pORI19. Transposition mutagenesis using the streptococcal temperature-sensitive
      suicide vector pTV408 to deliver Tn917 into the chromosome of L. garvieae was
      also achieved at a frequency of ca. 10(-4). Transposon flanking DNA sequences
      were obtained by plasmid rescue in Escherichia coli and their sequencing analysis
      demonstrated that the transposon was inserted at different chromosomal loci.
      Tn917 also made it possible to select a mutant in the operon involved in mannitol
      fermentation in this microorganism. The results obtained in the present study lay
      the foundation for future research on the virulence mechanisms of L. garvieae.

PMID- 16797930
TI  - The (ADP-ribosyl)ation reaction in thermophilic bacteria.
AB  - Species of Alicyclobacillus, Bacillus and Thermus genera were selected in order
      to study the possible presence of the (ADP-ribosyl)ation system. These bacteria
      are thermophilic, aerobic, and were isolated from different geothermal sources.
      Both activity and expression of (ADP-ribosyl)ating proteins were tested in cells
      at different growth phases, and evidence of an active system was obtained in all
      analyzed microorganisms, with comparable enzymatic levels. Immunochemical
      analyses with polyclonal antibodies against both eukaryotic anti-(ADP-ribose)
      transferase and anti-poly(ADP-ribose) polymerase revealed, for all tested
      organisms, an immunosignal localized in the range of molecular masses between 43
      53 kD. Several proteins of various molecular masses were found as ADP-ribose
      acceptors. Reaction product analyses showed mono(ADP-ribose) to be the only
      synthesized compound.

PMID- 16797931
TI  - Functional characterization of a novel hydrocarbonoclastic Pseudomonas sp. strain
      PUP6 with plant-growth-promoting traits and antifungal potential.
AB  - A novel hydrocarbonoclastic bacterium was isolated from rice rhizospheric soil
      using an enrichment culture technique. Detailed taxonomic studies identified the
      organism, designated strain PUP6, as a member of the genus Pseudomonas. The
      bacterium grew in minimal medium amended with n-alkane members of hydrocarbons, n
      dodecane (C12H26), n-hexadecane (C16H34), n-octadecane (C18H38), n-octacosane
      (C28H58); and petroleum fractions such as crude oil and lubricating oil when
      provided as sole carbon and energy source. Degradation of these n-alkane
      hydrocarbons and oils in minimal salts medium by strain PUP6 was estimated using
      gas chromatography with a flame ionization detector. In addition to its
      hydrocarbonoclastic properties, this bacterium exhibits a broad spectrum of
      fungal antibiosis against various phytopathogenic fungi. An antifungal metabolite
      produced by strain PUP6 was isolated, characterized and identified as phenazine-1
      carboxamide on the basis of nuclear magnetic resonance and mass spectroscopic
      analyses. Strain PUP6 also produced plant-growth-promoting siderophores,
      indoleacetic acid (IAA), phosphate solubilizing enzymes, and fungal cell wall
      degrading enzymes such as protease and chitinase. This study can be considered as
      the first report on n-alkane hydrocarbon and oil degradation by a rhizosphere
      soil bacterium that exhibits biofertilizing and biocontrol traits. Due to its
      innate multiple functional traits beyond its role in degradation of hydrocarbons,
      strain PUP6 may be used as plant-growth-promoting rhizobacterium and biocontrol
      agent against phytopathogenic fungi.

PMID- 16797933
TI  - Identification and characterization of secreted effector proteins of
      Chlamydophila pneumoniae TW183.
AB  - We report the expression of several chlamydial effector proteins in Chlamydophila
      pneumoniae, as well as their time-dependent secretion into the inclusion
      membrane. Localization of the respective genes within type III secretion gene
      clusters as well as bioinformatic analysis suggest that the identified proteins
      are type III-secreted effector proteins. Immunocytochemistry with antisera raised
      against CpMip (C. pneumoniae macrophage infectivity potentiator, Cpn0661), Pkn5
      (Cpn0703), Cpn0709, Cpn0712 and Cpn0827 showed secretion of the respective
      proteins into the inclusion membrane at 20 h postinfection (hpi). CpMip was
      detected within the inclusion membrane from 20 to 72 hpi, whereas Cpn0324 (CopN)
      was located in this compartment at 72 hpi only. This was confirmed by co
      localization of the respective proteins with IncA, an inclusion membrane marker
      protein. These data illustrate the fact that different effectors are being
      expressed and secreted during different time intervals of the infection cycle.
      Proteins Cpn0706 and Cpn0808 were not secreted by C. pneumoniae. The immunophilin
      FK506, known to inhibit the activity of Legionella, C. trachomatis and C.
      psittaci Mip proteins, was shown to interfere with chlamydial infection. Here we
      report the putatively type III-dependent secretion of CpMip into the inclusion
      membrane as well as the effect of its inhibition on C. pneumoniae infection of
      HEp-2 cells.

PMID- 16797932
TI  - Host resistance to Candida albicans infection of mice with collagen-induced
      arthritis treated with leflunomide.
AB  - The dehydro-orotate dehydrogenase inhibitor leflunomide is used for the treatment
      of rheumatoid arthritis. In the present study, its influence on host resistance
      to Candida albicans infection in mice with collagen-induced arthritis (CIA) was
      investigated. Leflunomide administered at a dose of 5 mg/kg for 5 consecutive
      days in mice with CIA inhibited collagen-specific cellular and humoral responses.
      The drug did not change the severity of primary C. albicans infection evaluated
      by kidney and liver colonization. At the early stage of infection leflunomide
      inhibited IFN-gamma production and enhanced IL-4 secretion. The effect of the
      drug on IL-4 production was less pronounced at the late phase of infection.
      Leflunomide enhanced anti-Candida IgM antibody production and diminished anti
      Candida IgG antibody synthesis. This correlated with impaired resistance to
      reinfection. Results demonstrate that leflunomide administration to mice with
      collagen-induced arthritis might affect mechanisms of the late immune response to
      C. albicans infection.

PMID- 16797935
TI  - Antibiotic cements in articular prostheses: current orthopaedic concepts.
AB  - The possibilities and limits of antibiotic cements (ACs) have been assessed by
      many researchers. ACs are now approved by many drug agencies, including the US
      Food and Drug Administration (approval in 2003), with widespread use in
      prophylaxis and curative treatments. Laboratory experiments have achieved
      satisfactory antibiotic delivery without impairing the mechanical properties of
      ACs. Implantation in large animals (e.g. sheep) showed an antibiotic
      concentration in the bone cortex four times the minimal inhibitory concentration
      (MIC) 6 months after implantation. Human pharmacokinetics during total hip
      replacement (THR) show antibiotic concentrations 20 times the MIC in drainage
      fluids. No toxic concentrations have been detected in blood or urine, and no
      allergies, toxic effects, mechanical failures or selection of resistant
      microorganisms have been observed. Antibioprophylaxis has been assessed in
      prospective studies in over 1600 cases. In data from the Scandinavian
      arthroplasty registers, with an exhaustive follow-up of more than 240000 THRs,
      infection rate was reduced by ca. 50% (0.9% compared with 1.9%). In prostheses
      with severe infection, use of AC increases the infection control rate from 86% to
      93% when using two-stage prosthetic exchanges. In moderate infection, a similar
      infection control rate (86%) was achieved either by two-stage exchange without
      local antibiotic or by one-stage exchange with AC; however, one-stage exchange
      achieved better functional results at lower cost and with reduced pain and
      hospital stay. Therefore, AC prophylaxis is widely used in countries with
      prostheses registers (Northern Europe), and use of ACs as treatment for infected
      prostheses is often considered as the gold standard in the EU and North America.
      However, AC is only an adjuvant treatment, and excision of infected and
      devascularized tissues as well as systemic antibiotic treatment managed by a
      multidisciplinary team remain the main factors of infection control.

PMID- 16797934
TI  - Molecular epidemiology and origin of cholera reemergence in Italy and Albania in
      the 1990s.
AB  - In 1994 a cholera epidemic occurred in Italy and Albania after more than a decade
      of case absence. To investigate genotypic characteristics and the origin of the
      epidemic strains, 110 Vibrio cholerae O1 El Tor isolates from Italy and Albania
      were studied by randomly amplified polymorphic DNA analysis (RAPD), BglI
      ribotyping, and pulsed-field gel electrophoresis (PFGE) of genomic DNA. The
      Italian and Albanian strains were all ribotype 6 and their RAPD and PFGE patterns
      were identical as well. These findings indicated that the 1994 isolates belonged
      to the same clone and that the clone was part of the larger global spread of
      epidemic ribotype 6 strains, which started in southern Asia in 1990.

PMID- 16797936
TI  - Acetylcholinesterase inhibitor donepezil in the treatment of cognitive deficit in
      schizophrenia. Subanalysis of the active branch from Czech extended double blind
      study.
AB  - The article mentions the conclusions of most evidential works investigating
      donepezil in the treatment of cognitive deficit in schizophrenia. It focuses on
      an analysis of a sub-group of 20 patients receiving treatment of the donepezil in
      an extended Czech double-blind placebo controlled study.

PMID- 16797937
TI  - The association of depression and painful physical symptoms--a review of the
      European literature.
AB  - OBJECTIVE: The presence of painful physical symptoms may confound the diagnosis
      of major depressive disorder and may worsen patient prognosis. Epidemiological
      literature was reviewed to investigate the association between depression and
      painful physical symptoms. METHOD: MEDLINE and EMBASE database searches were
      conducted. Studies where a definable organic basis for pain was given were
      excluded. The search was unrestricted by language but limited to European studies
      and countries. After filters were applied, 70 eligible studies were reviewed.
      RESULTS: The majority of studies reviewed showed an association between
      depression and painful physical symptoms. Over 40% of all studies examining the
      association between pain and depression were carried out in pain clinics in
      secondary care. Very few studies were conducted in psychiatric settings.
      CONCLUSION: The findings of this review suggest that painful physical symptoms
      may be an important part of the depressive syndrome. Although the relationship
      between depression and painful physical symptoms is not yet fully understood,
      findings suggest that diagnosis and treatment of depression should involve
      investigating and treating the full spectrum of symptoms (emotional and
      physical). Further research in psychiatric and generalist settings is needed to
      elucidate the relationship between depression and painful physical symptoms as
      experienced by patients and at the clinical level.

PMID- 16797938
TI  - Inhibition of HER-2(neu/ErbB2) restores normal function and structure to
      polycystic kidney disease (PKD) epithelia.
AB  - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a very common lethal
      monogenetic disease with significant morbidities and a high likelihood of
      progression to renal failure for which there is no proven disease-specific
      therapy currently available for clinical use. Human ADPKD cystic epithelia have
      proliferative abnormalities mediated by EGFR over-expression and mispolarization
      leading autocrine response to EGF family ligands. We now show that apical
      localization of EGFR complexes in normal fetal and ADPKD epithelia is associated
      with heterodimerization of EGFR(HER-1) with HER-2(neu/ErbB2), while basal
      membrane localization in normal adult renal epithelia is associated with EGFR(HER
      1) homodimers. Since ADPKD epithelial cells have reduced migratory function, this
      was used as a bioassay to evaluate the ability of compounds to rescue the
      aberrant human ADPKD phenotype. General tyrosine kinase inhibition by herbimycin
      and specific inhibition of HER-2(neu/ErbB2) by AG825 or pretreatment with ErbB2
      siRNA reversed the migration defect of ADPKD epithelia. Selective inhibition of
      EGFR(HER-1) showed partial rescue. Increased ADPKD cell migration after
      inhibition of p38MAP kinase but not of PI3-kinase implicated p38MAPK downstream
      of HER-2(neu/ErbB2) stimulation. Daily administration of AG825 to PKD1 null
      heterozygous mice significantly inhibited the development of renal cysts. These
      studies implicate HER2(neu/ErbB2) as an effector of apical EGFR complex
      mispolarization and that its inhibition should be considered a candidate for
      clinical therapy of ADPKD.

PMID- 16797939
TI  - Decreased choline and creatine concentrations in centrum semiovale in patients
      with generalized anxiety disorder: relationship to IQ and early trauma.
AB  - We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H
      MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral
      prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in
      comparison to healthy volunteers. A recent study indicates that the volume of
      prefrontal cortical white matter may be disproportionately increased in man in
      comparison to other primate species, with evolutionary implications. We therefore
      re-analyzed the identical scans with a specific focus on the centrum semiovale
      (CSO) as a representative region of interest of cerebral white matter. The
      central hypothesis was, in accordance with our gray matter findings, that
      patients with GAD, in comparison to healthy controls, would exhibit either an
      increase in NAA in CSO, or alternatively demonstrate reductions in concentrations
      of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI
      scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D.,
      Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral
      prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic
      resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119
      1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy
      age- and sex-matched volunteers were analyzed further for CSO metabolite
      alterations. Self-reported worry was scored using the Penn State Worry
      Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated
      Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been
      performed on a 1.5-T MRI. Using absolute quantification methods for metabolite
      concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited
      bilaterally decreased concentrations of CHO and CR in CSO in comparison to
      healthy volunteers, whereas GAD patients with ET were indistinguishable from
      controls. In patients with GAD, high IQ was paired with greater worry, whereas in
      healthy volunteers, high IQ was associated with less worry. In all subjects, IQ
      inversely predicted left and right CSO CHO concentrations, independent of age,
      sex, group assignment and PSWQ scores. The CSO may therefore represent a neural
      substrate that exhibits reductions in CHO and CR metabolite concentrations that
      are inversely associated with GAD symptomatology and, in the case of CHO, with
      intelligence. These conclusions are deemed preliminary due to small sample size,
      with further study of cerebral WM in anxiety disorders suggested.

PMID- 16797940
TI  - Preliminary findings of proton magnetic resonance spectroscopy in occipital
      cortex during sleep deprivation.
AB  - Proton magnetic resonance spectroscopy ((1)H MRS) has revealed biochemical
      alterations in various psychiatric disorders. Changes in brain metabolites may be
      caused not only by the disease's progression or response to treatment, but also
      by physiological variability. The aim of this study was to use (1)H MRS to assess
      the effects of specific short-term physiological states on major metabolites.
      Eight healthy women underwent (1)H MRS at the beginning and end of a 40-h period
      of sleep deprivation. The ratios of N-acetyl-aspartate (NAA), total creatine
      (tCr), and choline-containing compounds (Cho) to water (H(2)O) were determined
      from the occipital cortex during both baseline and photic stimulation conditions.
      During sleep deprivation, NAA/H(2)O decreased by 7% and Cho/H(2)O by 12%. Photic
      stimulation had no effect on the measured metabolites in the alert state, but in
      the sleep-deprived state the level of Cho/H(2)O increased during neuronal
      activation. The results suggest that NAA/H(2)O and Cho/H(2)O may depend on the
      state of alertness.

PMID- 16797941
TI  - Microbial adhesion to zirconium alloys.
AB  - We present data and analyses concerning the adhesion of clinically relevant
      Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa
      (bacteria) and Candida albicans (yeast) to Zircaloy-2 (Zry-2) and Zircadyne-705
      (Zr705) surfaces. These zirconium-based materials are similar to those now being
      used in total hip and knee replacements. Here we study clinical strains of
      microbes under shaken and stationary exposure conditions, and their ability to
      adhere to Zr surfaces having different oxide thicknesses. We use X-ray
      photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), viable
      counts, endotoxin assays, and statistical analysis methods, and demonstrate a
      predictive model for microbial adhesion based on XPS data.

PMID- 16797942
TI  - Release properties on gelatin-gum arabic microcapsules containing camphor oil
      with added polystyrene.
AB  - In this study, gelatin blended with arabic gum microcapsules containing camphor
      oil with added polystyrene were fabricated by a compound coacervation method. The
      parameters of oil/wall volume ratio, emulsification stirring speed, concentration
      of cross-linking agent, treated time and oil release properties were
      investigated. In order to improve the constant release effect of camphor oil, oil
      soluble polystyrene (PS) was used as a sustained release agent. The camphor oil
      release curves were expressed by the exponential equation: psi(t)=C(eq)(1-e(
      t/tau)), where psi(t) represent the variant of camphor oil concentration in the
      operation environment, C(eq) as the equilibrium state, t as the release time and
      tau as time constant. C(eq) and tau are significant factors pertaining to the
      camphor oil release properties. The results indicated that, for the
      microcapsules, the optimal oil/wall volume ratio was 0.75 to achieve the
      encapsulation efficiency of 99.6 wt.%. The average particle size were 294.7+/
      14.2 microm, 167.2+/-11.2 microm, 85.7+/-8.7 microm at the homogenization
      stirring speed of 500, 1000, and 2000 rpm, respectively. The effect of sustained
      oil release will increase whereas the stirring speed decreases and the
      concentration of glutaraldehyde (GA) and treated time increases. Along with the
      increasing of quantity of polystyrene added, C(eq) decreased and tau increased,
      indicating that the sustained oil release amount and the release rate depend on
      the quantity of PS considerably.

PMID- 16797944
TI  - Selective accumulation of light or heavy rare earth elements using gram-positive
      bacteria.
AB  - The accumulation of samarium from a solution only containing samarium by
      Arthrobacter nicotianae was examined. The amount of accumulated samarium was
      strongly affected by the concentration of samarium and pH of the solution. The
      accumulation of samarium by the strain was very rapid and reached equilibrium
      within 3h. The accumulation of samarium-europium or europium-gadolinium from the
      solution containing the two metals using various actinomycetes and gram-positive
      bacteria was also examined. Most of the tested strains could accumulate similar
      amounts of samarium and europium; however, most of the tested strains could
      accumulate a greater amount of europium than gadolinium. Especially, the amounts
      of accumulated europium using gram-positive bacteria were higher than those using
      actinomycetes. The selective accumulations of light or heavy rare earth elements
      (REEs) using A. nicotianae and Streptomyces albus were also examined. The amounts
      of accumulated samarium and europium were higher than those of the other light
      REEs using both microorganisms. S. albus can accumulate greater lutetium than
      other REEs from a solution containing yttrium and eight heavy REEs. On the other
      hand, A. nicotianae can accumulate higher amounts of terbium and ytterbium than
      that of the other heavy REEs from the same solution. A. nicotianae can also
      accumulated higher amounts of Sm than other REEs from a solution containing six
      light REEs.

PMID- 16797943
TI  - Protein adsorption from flowing solutions on pure and maleic acid copolymer
      modified glass particles.
AB  - The adsorption of human serum albumin (HSA) and lysozyme (LSZ) on pure as well as
      maleic acid (MA) copolymer coated spherical soda lime glass particles was
      investigated under flowing conditions. Coating the glass particles with two
      different maleic acid copolymers alters the properties of the particle surface
      concerning its charge and hydrophobicity in a well-defined gradation. Frontal
      chromatography was used to determine the surface concentration of the adsorbed
      proteins and to establish adsorption isotherms. The introduced methodology was
      demonstrated to provide a powerful means to study protein adsorption at
      solid/liquid interfaces. Investigations with virginal and protein-preadsorbed
      glass particles revealed that even under streaming conditions HSA is irreversibly
      adsorbed, whereas LSZ partially desorbs. For LSZ and HSA the adsorbed amounts and
      the isotherms strongly depend on the surface "history", i.e. the presence or
      absence of preadsorbed protein layers, and the kind of surface modification of
      the glass. Compared to the soda lime glass surface the adsorption of HSA was
      strongly increased on surfaces modified with a hydrophobic maleic acid copolymer
      indicating a strong hydrophobic protein-surface interaction. By coating the
      surface with a hydrophilic and more negatively charged maleic acid copolymer the
      adsorption of HSA to that surface was lower and comparable to the adsorption onto
      plain glass due to the electrostatic repulsion between HSA and the modified
      surface. In contrast the affinity to any of the investigated particle surfaces
      was generally higher for LSZ than for HSA which can be mainly attributed to the
      electrostatic attraction between LZS and the surface. The adsorbed amount of LSZ
      on the copolymer coated particle surfaces was much higher than on the pure soda
      lime glass particles indicating superposed hydrophobic interactions in the case
      of the hydrophobic MA copolymer layer and an increased density of anionic sites
      as well as interactions of LSZ within the three-dimensional (swollen),
      hydrophilic MA copolymer layer.

PMID- 16797945
TI  - Voltammetric determination of tyrosine based on an L-serine polymer film
      electrode.
AB  - A novel film electrode for the voltammetric determination of tyrosine has been
      constructed based on electropolymerization of L-serine on a glassy carbon
      electrode. Voltammetric behaviour of tyrosine on the poly-L-serine film electrode
      was investigated with cyclic voltammetry and linear sweep voltammetry, and
      electrochemical parameters were calculated from chronocoulometry. In optimal
      conditions, the oxidation peak current of tyrosine on the poly-L-serine film
      electrode was enhanced greatly. A sensitive oxidation peak at 0.90 V was employed
      to determine tyrosine. A linearity between the oxidation peak current and the
      tyrosine concentration was obtained in the range of 3.0 x 10(-7) to 1.0 x 10(-4)
      mol L(-1) with a detection limit of 1.0 x 10(-7)mol L(-1). The practical
      application of the film electrode in the determination of tyrosine in a
      commercial amino acid oral solution demonstrated that it has good selectivity and
      high sensitivity.

PMID- 16797946
TI  - Designing novel pH-sensitive non-phospholipid vesicle: characterization and cell
      interaction.
AB  - In this work, we report the preparation, the characterization and interaction
      with cells of novel pH-sensitive non-phospholipid vesicle formulations, from a
      non-ionic surfactant mixed with cholesterol (CHOL) and his derivative cholesteryl
      hemisuccinate (CHEMS), as pH-sensitive molecule. This molecule, can destabilize
      the vesicle lipid bilayer when exposed to an acidic environment, with a
      subsequent release of vesicular content, enhancing the cytoplasmatic delivery of
      drugs to target cells. Vesicles were characterized by static and dynamic light
      scattering, in order to evaluate their dimensions, bilayer thickness and vesicle
      stability. Membrane permeability changes were determined by the release of
      entrapped hydroxypyrene-1,3,6-trisulfonic acid (HPTS). Also diphenylhesatriene
      (DPH) fluorescence anisotropy and zeta potential measurements were used to
      evidence the pH sensitivity. Furthermore vesicles were characterized by means of
      electronic microscopy after freeze-fracture. The interaction of non-lipid
      vesicles containing different fluorescent dyes with Raw 264.7, mouse monocite
      macrophage, were analyzed by flow cytometric analysis. The obtained results
      indicate that the pH-sensitive vesicular structures show good plasma stability
      and relevant pH-sensitivity. Moreover this formulation was able to interact with
      target membranes (i.e. plasma or endosomal membrane) and to release the
      encapsulated material into the cytoplasm.

PMID- 16797947
TI  - [Maternal-fetal staphylococcal toxic shock syndrome with chorioamniotitis].
AB  - We report a rare case of mother-infant pair with Staphylococcal Toxic Shock
      Syndrome (TSS). A term neonate was born by caesarean section for maternal septic
      syndrome during per-partum. He presented with respiratory distress complicated by
      pulmonary hypertension, skin rash, and multiple organ system involvement.
      Staphylococcus aureus was isolated from placenta, surface swabs and gastric
      aspirate. He received adapted antibiotics, respiratory support by high frequency
      ventilation and NO. The mother had shock, skin rash and inflammatory syndrome.
      Outcome was good in both cases. The isolate produced enterotoxin C and L. Shock,
      exanthematous disease and multi-organ involvement complicating a staphylococcal
      infection in neonate must lead to suspect a TSS.

PMID- 16797948
TI  - Preparation and in vitro/in vivo evaluation of sustained-release metformin
      hydrochloride pellets.
AB  - In this study, metformin hydrochloride (MH) sustained-release pellets were
      successfully prepared by centrifugal granulation. Seed cores preparation, drug
      layering, talc modification and coating of polymeric suspensions were carried out
      in a centrifugal granulator. Talc modification was performed before coating in
      order to overcome the high water solubility of metformin. The influence of
      surface modification by talc, the effects of Eudragit types and ratios, as well
      as the correlation between in vitro release and in vivo absorption were
      investigated in detail. Experimental results indicated that talc modification
      made a decisive contribution to controlling the drug release by avoiding drug
      dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate
      buffer were employed to determine the in vitro release behaviors of the above
      metformin hydrochloride pellets. The relative bioavailability of the sustained
      release pellets was studied in 12 healthy volunteers after oral administration in
      a fast state using a commercially available immediate release tablet (Glucophage)
      as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit
      NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3),
      the pellets acquired perfect sustained-release properties and good relative
      bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3
      coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%,
      respectively. Combined use of two Eudragit polymers with different features as
      coating materials produced the desired results. Restricted delivery of metformin
      hydrochloride to the small intestine from differently coated pellets resulted in
      increased relative bioavailability and a sustained release effect. The adoption
      of several different pH dissolution media established a better relationship
      between the in vitro release and in vivo absorption of the sustained-release
      pellets.

PMID- 16797949
TI  - Agglomeration tendency in dry pharmaceutical granular systems.
AB  - The agglomeration tendency of dry pharmaceutical mixtures containing various
      concentrations of Xylitab 100 (Xylitol), calcium carbonate precipitated (CCP) and
      magnesium stearate (MgSt) was evaluated statistically as a function of mixing
      time. A Ro-Tap tester was employed to mix the three pharmaceutical components,
      and the agglomerates formed were measured with respect to their weight and size.
      An experimental design was devised and applied to structure and then
      statistically analyze the results. Xylitab was found not to be influential in the
      formation of agglomerates, but aided in deagglomeration when mixed with other
      components. CCP and MgSt formed agglomerates over time and showed positive
      interactions favouring agglomeration. The agglomerates started to fracture when
      they reached a critical size, at which stage the particles' attraction forces
      (cohesion forces) were weaker than both gravity and inertia. It has been shown
      and quantitatively demonstrated that the mixing time and ingredient
      concentrations of a three-component pharmaceutical mixture can affect
      agglomeration tendency.

PMID- 16797950
TI  - Investigation on physicochemical and biological differences of cefpodoxime
      proxetil enantiomers.
AB  - Cefpodoxime proxetil (CP) is a prodrug of cefpodoxime acid (CA), and is supplied
      as racemic mixture of R- and S-enantiomers. CP has only 50% absolute
      bioavailability, and the reasons responsible for low bioavailability remain
      poorly understood. The present work ascertains physicochemical and biological
      properties of individual isomers of CP and explores their capacity to optimize
      delivery of CP. Both isomers showed similar pH stability behavior, but R-isomer
      was more susceptible to enzymatic metabolism compared to S-isomer, when incubated
      with enzymes collected from various segments of GIT. Based on the in vitro and in
      vivo results, use of S-isomer for development of a dosage form such as gastro
      retentive dosage form can improve oral bioavailability of CP.

PMID- 16797951
TI  - Preparation of monolithic osmotic pump system by coating the indented core
      tablet.
AB  - A method for the preparation of monolithic osmotic pump tablet was obtained by
      coating the indented core tablet compressed by the punch with a needle. Atenolol
      was used as the model drug, sodium chloride as osmotic agent and polyethylene
      oxide as suspending agent. Ethyl cellulose was employed as semipermeable membrane
      containing polyethylene glycol 400 as plasticizer for controlling membrane
      permeability. The formulation of atenolol osmotic pump tablet was optimized by
      orthogonal design and evaluated by similarity factor (f2). The optimal
      formulation was evaluated in various release media and agitation rates.
      Indentation size of core tablet hardly affected drug release in the range of
      (1.00-1.14) mm. The optimal osmotic tablet was found to be able to deliver
      atenolol at an approximately constant rate up to 24h, independent of both release
      media and agitation rate. The method that is simplified by coating the indented
      core tablet with the elimination of laser drilling may be promising in the field
      of the preparation of osmotic pump tablet.

PMID- 16797952
TI  - Nasal immunization studies using liposomes loaded with tetanus toxoid and CpG
      ODN.
AB  - To increase the systemic and mucosal immune responses against the nasally
      administered tetanus toxoid, liposomes as a drug delivery system and CpG-ODN as
      an adjuvant were evaluated. Rabbits were nasally immunized with entrapped tetanus
      toxoid (TT) and CpG-ODN in neutral liposomes and systemic and mucosal immune
      responses were determined. Liposomes containing TT and CpG-ODN were prepared by
      dehydration-rehydration method. The volume mean diameter of liposomes was 2.3+/
      0.6 microm. Encapsulation efficiency of TT and CpG-ODN was determined as 54.0+/
      8.8 and 60.1+/-7.4, respectively. The leakage of the encapsulated TT from
      liposomes reached 7.38% after 3 months. Encapsulated TT kept its intact
      structure, and its immunoreactivity was also completely preserved, as shown by
      SDS-PAGE and ELISA methods. The highest serum IgG and antitoxin titers were
      observed in groups immunized with solution formulations (P < 0.001). However the
      highest mucosal sIgA titers were achieved by liposomes encapsulated with TT. CpG
      ODN as an adjuvant was able to increase the serum IgG and antitoxin titers when
      co-administered with TT solution (P < 0.05) or co-encapsulated with TT in
      liposomes (P < 0.01), but failed to increase the sIgA titers in nasal lavages. No
      hemolysis occurred on incubation of liposomes and human RBCs. Also after nasal
      administration of plain liposomes to human volunteers, no local irritation was
      seen. Intranasal administration of liposomes encapsulated with vaccines showed to
      be an effective way for inducing the mucosal immune responses.

PMID- 16797953
TI  - A novel method to prepare highly encapsulated interferon-alpha-2b containing
      liposomes for intramuscular sustained release.
AB  - A novel modified film-hydration-dilution method was employed to prepare highly
      encapsulated interferon-alpha-2b containing liposomes for intramuscular sustained
      release. The liposomes produced by this technique were a mixture of mainly
      unilamellar vesicles and a small number of multilamellar vesicles. The trapping
      efficiency was above 80%. With at least 60-fold dilution, Triton X-100 at the
      concentration of 0.3% (w/v) in phosphate buffered saline (PBS) was able to
      solubilize phospholipids without denaturing the protein and/or interfering with
      the enzyme-linked immunoassay (ELISA). After three homogenization cycles under a
      pressure of 70 MPa the size of liposomes was reduced from 978 to 101 nm while the
      activity of interferon-alpha-2b decreased by 9.9% compared to the control.
      Although liposomes were physically stable for 22 months at 4 degrees C the mean
      size of the liposomes increased slightly from 101 to 122 nm. The levels of free
      interferon-alpha-2b at the site of intramuscular injection decreased rapidly with
      only 4.15% of initial dose retained at the injection site after 0.33 h following
      injection of an interferon-alpha-2b solution (nonencapsulated). In contrast,
      interferon-alpha-2b encapsulated in liposomes was retained at the site of
      intramuscular injection at higher levels than free interferon-alpha-2b (p <
      0.05). Larger liposomes containing interferon-alpha-2b (978 nm) were the most
      effective for local retention because 27.8% of interferon-alpha-2b was retained
      after 24 h. These liposomes have the potential to be topically injected for
      treating genital herpes with prolonged interferon levels at the local injection
      site. Since the smaller liposomes (75.8 and 101 nm) retained interferon-alpha-2b
      at the injection site for shorter times while enhancing the blood circulation of
      the drug, they are potentially good carriers for systemic therapy with higher
      bioavailability and liver targeting.

PMID- 16797955
TI  - Application of simulation models to the diagnosis of MSW landfills: an example.
AB  - Among the landfill simulation programs being developed by several research groups
      around the world as tools for the management of sanitary landfills is MODUELO,
      whose second version, MODUELO 2, has been presented elsewhere. It reproduces the
      operational history of the landfill and its hydrologic and biodegradation
      processes, allowing the estimation of the flow and pollutants emitted in the
      leachate and the generated landfill gas over time. This program has been used for
      a diagnosis study of an existing European MSW landfill. The construction and
      calibration of the facility's hydrologic model, based on the available data,
      allowed the detection and quantification of two sources increasing the flows
      reaching the leachate collection system: a small portion (6-7%) of the runoff
      over the landfill surface and the contribution of water coming from external
      hillsides of the same watershed that represent a total surface area of around
      20ha. The contrast of the leachate quality (COD, BOD, NH(4)-N and TKN) simulation
      results and measured data showed the potential of these models for the assessment
      of other significant aspects in landfill operation such as the potential
      harnessing of the landfill gas. Nonetheless, in this case as in many others, the
      accuracy of the simulation results was limited by the scant quality of the
      available data, which highlights the need for implementing continuous monitoring
      and characterizing protocols to take advantage of these programs as a tool for
      landfill optimization.

PMID- 16797954
TI  - Occurrence of laccases in lichenized ascomycetes of the Peltigerineae.
AB  - Following our previous findings of high extracellular redox activity in lichens,
      the results of the work presented here identify the enzymes involved as laccases.
      Despite numerous data on laccases in fungi and flowering plants, this is the
      first report of the occurrence of laccases in lichenized ascomycetes.
      Extracellular laccase activity was measured in 40 species of lichens from
      different taxonomic groupings and contrasting habitats. Out of 20 species tested
      from suborder Peltigerineae, 18 displayed laccase activity, while activity was
      absent in species tested from other lichen groups. Identification of the enzymes
      as laccases was confirmed by the ability of lichen leachates to readily
      metabolize substrates such as 2,2'-azino(bis-3-ethylbenzthiazoline-6-sulfonate)
      (ABTS), syringaldazine and o-tolidine in the absence of hydrogen peroxide,
      sensitivity of the enzymes to cyanide and azide, the enzymes having typical
      laccase pH and temperature optima, and an absorption spectrum with a peak at
      614nm. Desiccation and wounding stimulated laccase activity. Laccase activity was
      not increased after treatment with normal inducers of laccase synthesis,
      suggesting that they are constitutively expressed. Electrophoresis showed that
      the active form of laccase from Peltigera malacea was a tetramer with an
      unusually high molecular mass of 340kDa and an isoelectric point (pI) of 4.7. The
      finding of abundant extracellular redox enzymes known to actively produce
      reactive oxygen species suggest that their roles may include increasing nutrient
      supply to lichens by delignification, and deterring pathogens by contributing to
      the oxidative burst. Furthermore, once released into the environment, they may
      participate in the carbon cycle by facilitating the breakdown or formation of
      humic substances.

PMID- 16797956
TI  - Kinetics and dynamic modelling of batch anaerobic digestion of municipal solid
      waste in a stirred reactor.
AB  - A series of batch, slurry anaerobic digestion experiments were performed where
      the soluble and insoluble fractions, and unwashed MSW were separately digested in
      a 200l stirred stainless steel vessel at a pH of 7.2 and a temperature of 38
      degrees C. It was found that 7% of the total MSW COD was readily soluble, of
      which 80% was converted to biogas; 50% of the insoluble fraction was solubilised,
      of this only 80% was converted to biogas. The rate of digesting the insoluble
      fraction was about four times slower than the rate of digesting the soluble
      fraction; 48% of the total COD was converted to biogas and 40% of the total
      nitrogen was converted to ammonia. Soluble and insoluble fractions were broken
      down simultaneously. The minimum time to convert 95% of the degradable fraction
      to biogas was 20 days. The lag phase for the degradation of insoluble fraction of
      MSW can be overcome by acclimatising the culture with the soluble fraction. The
      rate of digestion and the methane yield was not affected by particle size (within
      the range of 2-50mm). A dynamic model was developed to describe batch digestion
      of MSW. The parameters of the model were estimated using data from the separate
      digestion of soluble and insoluble fractions and validated against data from the
      digestion of unwashed MSW. Trends in the specific aceticlastic and formate
      utilising methanogenic activity were used to estimate initial methanogenic
      biomass concentration and bacterial death rate coefficient. The kinetics of
      hydrolysis of insoluble fraction could be adequately described by a Contois
      equation and the kinetics of acidogenesis, and aceticlastic and hydrogen
      utilising methanogenesis by Monod equations.

PMID- 16797957
TI  - Agro-industry sugarcane residues disposal: the trends of their conversion into
      energy carriers in Cuba.
AB  - The goal of the present work was to carry out a review of the disposal practices
      for the agro-industry's sugarcane residue and the trends of energy use in Cuba.
      The lack of an alternative energy carrier to electricity with storage capability
      for use in off-season has to date been an unsolvable question. The improvement of
      cogeneration capacity via implementation of CEST or BIG/GTCC and the barriers for
      their implementation, the introduction of a medium size (3 ton/h) fast pyrolysis
      module (FPM3) as a solution for off-season energy demand in the agro-industry,
      and an assessment of the energy required to do so, were also analyzed. Bio-oil
      production from bagasse and sugarcane agriculture residues (SCAR) and their
      particularities at the sugar mill are treated. The influence of sugar facility
      production process configuration is analyzed. The fast pyrolysis products and the
      trends of their end uses in Cuba are presented. The production cost of a ton of
      Bio-oil for FPM3 conditions was calculated at 155 USD/ton and the payback time as
      a function of selling price between 160 and 110 USD/ton was estimated to be from
      1.5 to 4 years. The economic feasibility of the FPM3 was estimated, comparing the
      added values for three scenarios: 1st case, currently-used sugar production, 16.5
      USD/ton of cane; 2nd case, factoring in the cogeneration improvement, 27 USD/ton
      of cane; and 3rd case, with cogeneration improvement and Bio-oil production, 40
      USD/ton of cane. The energy use of SCAR and the introduction of FPM3 in the sugar
      mill are promising improvements that could result in a potential surplus of 80
      kWh(e)/ton of cane in-season, or 6 x 10(6)ton of Bio-oil (LHV=15 MJ/kg) for use
      off-season in a milling season of 4 million tons of raw sugar.

PMID- 16797958
TI  - Chemically imaging living cells by scanning electrochemical microscopy.
AB  - Scanning electrochemical microscopy (SECM) is useful in probing and
      characterizing interfaces at high resolution. In this paper, the general
      principles of this technique are described and several applications of SECM to
      biological systems, particularly to living cells, is discussed, along with
      several example systems. Thiodione was detected and monitored electrochemically
      during the treatment of hepatocytes with cytotoxic menadione. The antimicrobial
      effects of silver(I) was followed by SECM through bacterial respiration. Living
      HeLa cells were shown to accumulate ferrocencemethanol (FcMeOH) and generated
      positive feedback for FcMeOH oxidation that can be further used to monitor the
      cell viability. Finally, individual giant liposomes, as cell models, with
      encapsulated redox compounds were successfully probed by SECM. In general SECM
      has the advantage of very high spatial resolution and versatility, especially for
      the detection of electroactive substances.

PMID- 16797959
TI  - A label-free electrochemical immunoassay for carcinoembryonic antigen (CEA) based
      on gold nanoparticles (AuNPs) and nonconductive polymer film.
AB  - A simple and sensitive label-free electrochemical immunoassay electrode for
      detection of carcinoembryonic antigen (CEA) has been developed. CEA antibody
      (CEAAb) was covalently attached on glutathione (GSH) monolayer-modified gold
      nanoparticle (AuNP) and the resulting CEAAb-AuNP bioconjugates were immobilized
      on Au electrode by electro-copolymerization with o-aminophenol (OAP).
      Electrochemical impedance spectroscopy and cyclic voltammetry studies demonstrate
      that the formation of CEA antibody-antigen complexes increases the electron
      transfer resistance of [Fe(CN)(6)](3-/4-) redox pair at the poly-OAP/CEAAb
      AuNP/Au electrode. The use of CEA antibody-AuNP bioconjugates and poly-OAP film
      could enhance the sensitivity and anti-nonspecific binding of the resulting
      immunoassay electrode. The preliminary application of poly-OAP/CEAAb-AuNP/Au
      electrode for detection of CEA was also evaluated.

PMID- 16797960
TI  - Visual DNA microarrays for simultaneous detection of Ureaplasma urealyticum and
      Chlamydia trachomatis coupled with multiplex asymmetrical PCR.
AB  - Visual DNA microarrays, based on gold label silver stain (GLSS) and coupled with
      multiplex asymmetrical PCR, were developed for simultaneous, sensitive and
      specific detection of Ureaplasma urealyticum and Chlamydia trachomatis. 5'-end
      amino-modified oligonucleotides, which were immobilized on glass surface, acted
      as capturing probes that were designed to bind complementary biotinylated targets
      DNA. The gold-conjugated streptavidins were introduced to the microarray for
      specific binding to biotin. The black image of microarray spots, resulting from
      the precipitation of silver onto nanogold particles bound to streptavidins, were
      used to detect biotinylated targets DNA visually or with a visible light scanner.
      Multiplex asymmetrical PCR of U. urealyticum, C. trachomatis and Bacillus
      subtilis (used as positive control) was performed to prepare abundant
      biotinylated single-stranded targets DNA, which affected detection efficiency and
      sensitivity of hybridization on microarray. Plenty of clinical samples of U.
      urealyticum and C. trachomatis from infected patients were tested using home-made
      DNA microarrays. For its high sensitivity, good specificity, simplicity,
      cheapness and speed, the present visual gene-detecting technique has potential
      applications in clinical fields.

PMID- 16797961
TI  - Natural and synthetic affinity agents as microdialysis sampling mass transport
      enhancers: current progress and future perspectives.
AB  - Microdialysis sampling is a diffusion-based separation method that allows
      analytes to freely diffuse across a hollow fiber semi-permeable dialysis
      membrane. This sampling technique has been widely used for in vivo chemical
      collection. The inclusion of affinity-based trapping agents into the
      microdialysis perfusion fluid serves to improve the relative recovery via the
      binding reaction of low molecular weight hydrophobic analytes and larger analytes
      such as peptides and proteins. Here, we briefly review our past studies using
      different compounds (native cyclodextrins and antibodies) to improve
      microdialysis sampling recovery. A brief compilation of our studies using
      antibody-immobilized beads as a means to improve cytokine collection during
      microdialysis sampling is also described. We present new work focused on the use
      of antibody-immobilized bead microdialysis sampling enhancement for various
      endocrine hormones (amylin, GLP-1, glucagon, insulin, and leptin). The antibody
      bead enhancement approach allowed for recovery enhancements that ranged between 3
      and 20-fold for these peptides. Using the enhanced recovery approach, endocrine
      peptides at pM concentrations can be quantified. Finally, our initial work
      focused on developing non-antibody based enhancement agents using bovine serum
      albumin-heparin conjugates covalently bound to polystyrene microspheres is
      presented for the cytokine, tumor necrosis factor-alpha (TNF-alpha). Unlike
      antibodies, heparin provides the advantage of being reusable as an enhancement
      agent and served to improve the relative recovery of TNF-alpha by three-fold.

PMID- 16797962
TI  - Nucleic acid sensing by regenerable surface-associated isothermal rolling circle
      amplification.
AB  - A novel method for regenerating biosensors has been developed in which the highly
      specific detection of nucleic acid sequences is carried out using molecular
      padlock probe (MPP) technology and surface-associated rolling circle
      amplification (RCA). This technique has a low occurrence of false positive
      results when compared to polymerase chain reaction, and is an isothermal
      reaction, which is advantageous in systems requiring low power consumption such
      as remote field sensing applications. Gold-sputtered 96-well polystyrene
      microplates and a fluorescent label were used to explore the detection limits of
      the surface-associated RCA technique, specificity for different MPP, conditions
      for regeneration of the biomolecular sensing surface, and reproducibility of
      measurements on regenerated surfaces. The technique was used to create highly
      selective biomolecular surfaces capable of discriminating between DNA
      oligonucleotides with sequences identical to RNA from infectious salmon anemia
      (ISA) and infectious hematopoietic necrosis (IHN) virus. As little as 0.6 fmol of
      circularized MPP was detectable with this fluorimetric assay. The sensing layers
      could be reused for at least four cycles of amplification using thermal
      denaturation, with less than 33% decrease in RCA response over time. Because the
      nucleic acid product of the test is attached to a surface during amplification,
      the technique is directly applicable to a variety of existing sensing platforms,
      including acoustic wave and optical devices.

PMID- 16797963
TI  - Gastrulation in zebrafish -- all just about adhesion?
AB  - During vertebrate gastrulation, the evolutionarily conserved morphogenetic
      movements of epiboly, internalization, convergence and extension cooperate to
      generate germ layers and to sculpt the body plan. In zebrafish, these movements
      are driven by a variety of cell behaviors, including slow and fast directed
      migration, radial and mediolateral intercalation, and cell shape changes. Whereas
      some signaling pathways are required for a subset of these behaviors, other
      molecules, such as E-cadherin or Galpha12 and Galpha13 proteins, appear to have a
      widespread role in different gastrulation cell behaviors.

PMID- 16797964
TI  - Single-molecule studies of membrane proteins.
AB  - Characterizing membrane proteins with single-molecule techniques provides
      structural and functional insights that cannot be obtained with conventional
      approaches. Recent studies show that atomic force microscopy (AFM) in the context
      of a 'lab on a tip' enables the measurement of multiple parameters of membrane
      proteins. This multifunctional tool can be applied to probe the oligomeric states
      and conformational changes of membrane protein assemblies in their native
      environment. The ability to determine diverse properties at high spatial
      resolution facilitates the mapping of structural flexibilities, electrostatic
      potentials and electric currents. By using the AFM tip as tweezer, it is possible
      to characterize unfolding and refolding pathways of single proteins and the
      location of their molecular interactions. These interactions dictate the
      stability of the protein and might be modulated by ligands that alter the
      protein's functional state.

PMID- 16797966
TI  - Active immunotherapy of multiple myeloma.
AB  - Since myeloma cells express various potential target antigens, active
      immunotherapy is being investigated as a novel treatment modality for myeloma.
      Immunization against the clonal myeloma immunoglobulin (idiotype) elicits
      protective immunity in mouse models. Idiotype vaccination of myeloma patients can
      induce cellular immunity, albeit as yet without firm evidence for improved
      clinical outcome. Other tumour-associated antigens (including cancer/testis
      antigens) are expressed with various frequencies in myeloma. T cells with
      specificity for these antigens may exist in myeloma patients, and immunization
      trials with some of these antigens are ongoing. Future studies need to identify
      the best antigen, the optimal vaccine formulation and schedule, and the
      preferable clinical situation for vaccination with myeloma antigens. In addition,
      immunization of stem cell donors with myeloma antigens may improve the efficacy
      and outcome of allogeneic stem cell transplantation through transfer of idiotype
      directed immunity to the patient, and has already shown promising clinical
      results.

PMID- 16797965
TI  - Angiogenesis in multiple myeloma.
AB  - Multiple myeloma (MM) was the first haematological malignancy in which a
      prognostic relevance of bone marrow microvessel density (MVD) was shown. Myeloma
      induced angiogenesis involves either the direct production of angiogenic
      molecules by myeloma cells or their induction in bone marrow stromal cells or
      endothelial cells (EC). Recent data demonstrate an increased angiogenic potential
      and a paracrine stimulatory effect of bone marrow EC on plasma cells (PC) in MM.
      Soluble angiogenic factors are elevated in bone marrow (BM) and in peripheral
      blood samples from myeloma patients. Furthermore, correlation with disease stage
      and prognosis was shown for serum levels of the angiogenic factors basic
      fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and vascular
      endothelial growth factor (VEGF). In this review we summarize recent data which
      give strong evidence for an increased angiogenic activity in bone marrow
      microenvironment and support the hypothesis that angiogenesis is not only an
      epiphenomenon of tumour growth but may also promote PC growth in MM.

PMID- 16797967
TI  - Elderly patients with rectal cancer have a higher risk of treatment-related
      complications and a poorer prognosis than younger patients: a population-based
      study.
AB  - It is likely that the shift from post- to pre-operative radiotherapy and the
      introduction of total mesorectal excision (TME) surgery have contributed to the
      observed improved survival of rectal cancer in the south of the Netherlands.
      However, no improvement was seen for patients aged 70 or older. To investigate
      possible causes of this lack of improvement, we examined the risk of treatment
      related complications and overall survival. Therefore, a random sample of 455
      patients with rectal cancer aged 60 years or older, diagnosed between 1995 and
      2001 was extracted from in the Eindhoven Cancer Registry database. Fifty-one
      percent of patients aged 60-69 years-old had any complication within one year of
      diagnosis compared to 65% of patients aged 70 or older (p=0.007). Older patients
      were at higher risk of developing treatment-related complications (odds ratio
      (OR) 1.8; p=0.01), as were patients with comorbidity (OR 1.7; p=0.07), and those
      who received pre-operative radiotherapy (OR 1.8; p=0.02). In a multivariable
      analysis, age older than 70 (hazard ratio (HR) 2.2; p<0.0001), comorbidity (HR
      1.7; p=0.03), and having two or more complications (HR=2.2; p=0.0002) had a
      negative effect on survival. The lack of improvement in the prognosis of elderly
      patients with rectal cancer after a shift from post- to preoperative radiotherapy
      might partially be explained by a higher risk of treatment-related complications.
      In order to optimise the risk/benefit ratio of elderly patients,
      individualisation of treatment by means of a comprehensive geriatric assessment
      will be of critical importance.

PMID- 16797968
TI  - Re-analysis of the Xq27-Xq28 region suggests a weak association of an X-linked
      gene with sporadic testicular germ cell tumour without cryptorchidism.
AB  - BACKGROUND: A testicular germ cell tumour (TGCT) predisposing gene has been
      mapped to the Xq27 region on the X chromosome. These linkage findings remain to
      be confirmed by other studies. METHODS: In 276 patients and 169 unaffected first
      degree male relatives, 12 microsatellite markers covering the candidate region
      were genotyped and used to study possible association of TGCT with Xq27. RESULTS:
      In contrast to previously reported linkage of familial TGCT and cryptorchidism
      with Xq27, we observed an association between the subset of TGCT cases without a
      family history of TGCT or cryptorchism and marker DXS1193 (p=0.014). Carriers of
      minor alleles were at increased risk (odds ratio (OR) 4.7, confidence interval
      (CI) 1.1-19.6) CONCLUSION: We found an association on Xq27 in a subset of TGCT
      cases, which suggests the presence of an X-linked gene that slightly or
      moderately increases risk to develop sporadic TGCT but not cryptorchidism.

PMID- 16797969
TI  - Multiple myeloma: monoclonal antibodies-based immunotherapeutic strategies and
      targeted radiotherapy.
AB  - Multiple myeloma (MM) is an incurable B-cell malignancy of terminally
      differentiated plasma cells. Besides conventional treatments, several targeted
      therapies are emerging for MM. We review recent developments in monoclonal
      antibodies (MoAbs) and (radio)immunoconjugates-based targeted immunotherapeutic
      (serotherapies) strategies, as well as skeletal targeted radiotherapy (STR) in
      MM. MoAbs-based strategies include the targeting of cytokines and their receptors
      as well as toxins, drugs or radionuclide delivery to MM cells. Both targeted
      radioimmunotherapy (RIT) and STR have proved efficient in the treatment of
      radiosensitive tumours. We conclude that there is a need for more mechanistic
      investigations of drug action to identify novel therapeutic targets in myeloma
      cells, as well as in the bone marrow microenvironment.

PMID- 16797970
TI  - Signalling and survival pathways in multiple myeloma.
AB  - The main factors that govern the pathophysiology and malignant growth of multiple
      myeloma (MM) are genetic defects within the tumour and the interaction between
      myeloma cells and the bone marrow microenvironment (BMM). This interaction leads
      to the activation of signalling pathways that promote the expansion of the
      malignant clone and stimulate neoangiogenesis and osteoclastogenesis. For many
      years, the cytokine interleukin-6 (IL-6) was considered a central growth factor
      and was thus believed to play a pivitol role in the pathogenesis of MM. However,
      increasing numbers of cytokines, chemokines and cell-to-cell contacts provided by
      the BMM have since been found to support MM cells. It has consistently been
      demonstrated that oncogenic mutations as well as the BMM stimulate IL-6
      independent signalling pathways that protect MM cells from apoptosis.
      Consequently, multiple targeting of a complex signalling network rather than
      inhibition of a single pathway or growth factor is required to effectively induce
      myeloma cell death. Because the tumour suppressor p53 is rarely mutated in MM,
      non-genotoxic activation of the p53-dependent death pathway could be another
      attractive therapeutic strategy for this disease. Even though a number of
      promising new drugs are currently being tested in MM, a comprehensive knowledge
      of the signalling and survival pathways should pinpoint additional molecular
      targets and lead to the development of novel and hopefully more effective
      treatment strategies.

PMID- 16797971
TI  - Myeloma bone disease and treatment options.
AB  - Multiple myeloma (MM) is a B-cell malignancy characterized by enhanced bone loss
      commonly associated with a diffuse osteopenia, focal lytic lesions, pathologic
      fractures, hypercalcemia, and bony pain. Bone destruction in MM results from
      asynchronous bone turnover wherein increased osteoclastic bone resorption is not
      accompanied by a comparable increase in bone formation. Recent characterization
      of osteoclast-activating factors (OAFs), receptor activator of nuclear factor
      kappaB (RANK) ligand (RANKL)-osteoprotegerin-RANK system, and inhibitors of Wnt
      signaling have provided a better understanding of myeloma bone disease in
      molecular level. The development of minimally invasive surgical procedures such
      as kyphoplasty and vertebroplasty allows myeloma patients with vertebral
      compression fractures to have immediate improvement in quality of life and
      shorter hospital stays. Monthly intravenous infusion of either pamidronate or
      zoledronic acid have reduced the skeletal complications among MM patients and are
      now a mainstay of myeloma therapy. Orally administered bisphosphonates, in
      contrast, have shown little ability to slow the development of skeletal
      complications in these patients. Although pre-clinical studies suggest nitrogen
      containing bisphosphonates have potent anti-tumor effects, clinical trials will
      be necessary, probably at higher doses given more slowly, to establish their
      possible anti-tumor effects clinically. As our understanding of the
      pathophysiology of myeloma bone disease continues to increase, new target
      therapies will continue to emerge offering new and more advanced options for the
      management of myeloma bone disease.

PMID- 16797972
TI  - Clinical molecular imaging with positron emission tomography.
AB  - Molecular imaging allows for the in vivo evaluation of targeted molecules and
      biological processes in man. Positron emission tomography (PET) is a highly
      sensitive and quantitative molecular imaging modality, whose utility in clinical
      and experimental medicine is increasing by the day. In this article, the
      principles of PET and its currently accepted applications in oncology, such as
      cancer staging, treatment response assessment and as a prognostic marker are
      reviewed. Further, the evolving role of PET in areas of oncology such as
      radiotherapy treatment planning, anti-cancer drug development and the evaluation
      of patho-physiological processes which drive a cell into neoplastic activity is
      discussed.

PMID- 16797973
TI  - Hypoxic activation of unoccupied estrogen-receptor-alpha is mediated by hypoxia
      inducible factor-1 alpha.
AB  - The estrogen receptor (ER) plays an important role in breast cancer development
      and progression. Hypoxia has been shown to modulate the level of ERalpha
      expression, which is intimately associated with the biology of breast carcinomas.
      However, the effect of hypoxia on ERalpha-mediated transactivation is largely
      unknown. In this report, we have examined ligand-independent transcriptional
      activation of ERalpha by hypoxia. The hypoxia-induced ERalpha-mediated
      transcriptional response was inhibited by the ER antagonist ICI 182,780 as
      determined by transient expression of ERalpha and ER-responsive reporter plasmids
      in the HEK 293 cells. Hypoxic activation of ERalpha was dependent on the
      increased expression of hypoxia-inducible factor-1alpha (HIF-1alpha), as examined
      in HEK 293 cells under conditions of normoxia. These results indicate that
      hypoxia activates ERalpha in a ligand-independent manner, possibly through the
      interaction between HIF-1alpha and ERalpha.

PMID- 16797974
TI  - Optimization of native agar extraction from Hydropuntia cornea from Yucatan,
      Mexico.
AB  - Response surface methodology (RSM) was used to determine optimum extraction
      conditions for yield, gelling temperature, melting temperature and apparent
      viscosity of native agar from the red alga Hydropuntia cornea. Two independent
      variables were selected during extraction, temperature (80, 90 and 100 degrees C)
      and time (2, 3 and 4 h). The extraction procedure using 100 degrees C and 3 h
      produced the greatest yield (43.3%), the greatest gelling temperature (32 degrees
      C) and the greatest melting temperature (78 degrees C). The extraction using 65
      degrees C and 4 h produced the optimum statistical apparent viscosity (80.73
      cPs), though agar yield under these conditions had low quality for industrial
      purposes. Temperature and time do not affect melting temperature, but do play an
      important role in gelling temperature. From the independent variables studied,
      extraction temperature is most important in producing an increase in yield, and
      time is the only variable that contributes significantly to increasing viscosity.
      Most of the physicochemical properties found in the native agar from H. cornea
      extracted at 100 degrees C/3 h were similar to commercial samples. These findings
      suggest the feasibility of using this colloid in spreads and soft-texture food
      products.

PMID- 16797975
TI  - Effect of plant growth on dehydration rates and microbial populations in sewage
      biosolids.
AB  - The high water content of sewage biosolids makes them expensive to transport. Two
      experiments were done to see if it was practical to use transpiration by plants
      as a low cost method to dehydrate biosolids. (i) To assess biosolids as a growth
      medium for plants, maize, beans, pumpkin, forage oats and an annual ryegrass were
      grown in pots of fresh biosolids. Plant growth varied between species and
      potassium deficiency was found to be a limiting factor for barley. Roots were
      slow to penetrate anoxic biosolids in the bottom of the pots. (ii) Dehydration
      rates were measured in 30 litre boxes of biosolids from two different sources.
      Boxes were planted with maize or beans, or kept fallow. Despite the high (73-83%)
      initial water content of the biosolids, plants were susceptible to wilting on
      warm days which suggested that a significant proportion of the water in biosolids
      is not freely available to plants. Shrinkage caused a major reduction in
      biosolids volume in both experiments. When change in volume of the biosolids
      residue was accounted for, there was a 56% average water loss in planted
      treatments and 34% water loss in the fallow treatment. This indicates that
      planting may have some potential as a technique to accelerate dehydration of
      biosolids. Water contents were not reduced sufficiently to influence biosolids
      microbial populations.

PMID- 16797976
TI  - Microbial hydrogen production with Bacillus coagulans IIT-BT S1 isolated from
      anaerobic sewage sludge.
AB  - Bacillus coagulans strain IIT-BT S1 isolated from anaerobically digested
      activated sewage sludge was investigated for its ability to produce H(2) from
      glucose-based medium under the influence of different environmental parameters.
      At mid-exponential phase of cell growth, H(2) production initiated and reached
      maximum production rate in the stationary phase. The maximal H(2) yield (2.28 mol
      H(2)/molglucose) was recorded at an initial glucose concentration of 2% (w/v), pH
      6.5, temperature 37 degrees C, inoculum volume of 10% (v/v) and inoculum age of
      14 h. Cell growth rate and rate of hydrogen production decreased when glucose
      concentration was elevated above 2% w/v, indicating substrate inhibition. The
      ability of the organism to utilize various carbon sources for H(2) fermentation
      was also determined.

PMID- 16797977
TI  - NH(4)OH-KOH pulping mechanisms and kinetics of rice straw.
AB  - The mechanisms and kinetics of NH(4)OH-KOH mixture pulping rice straw were
      studied. When aqueous ammonia was mixed with a small amount of caustic potash
      (ratio of 1:5), three distinct delignification phases were observed in the
      pulping process: a bulk delignification phase from the beginning of the cooking
      period to 100 degrees C, a supplementary delignification phase from 100 degrees C
      to 155 degrees C lasting a further 45 min, and a residual delignification phase
      until the end of the cooking period. There were two silica removal phases; the
      first phase was from the beginning of the cooking period to 100 degrees C and the
      second phase was from 100 degrees C to the end of the cooking period. The rate of
      delignification reaction was first order with respect to residual lignin and 0.3
      order with respect to [OH(-)]. The silica removal was pseudo-first-order with
      respect to residual silica and 0.6 order with respect to [OH(-)]. The activation
      energies of the delignification and removal of silica reactions were 35.6 and
      30.9 kJ/mol, respectively.

PMID- 16797978
TI  - Switchgrass (Panicum vigratum, L.) delivery to a biorefinery using integrated
      biomass supply analysis and logistics (IBSAL) model.
AB  - This study develops cost, energy input and carbon emissions for a number of
      switchgrass supply options. The Integrated Biomass Supply Analysis and Logistics
      (IBSAL) model developed at Oak Ridge National Laboratory is used to evaluate the
      delivery systems. Three biomass collection systems: baling, loafing and ensiling
      are evaluated. The number and operational performance of equipment are specified
      to complete collection operations within 120 days of harvest after August 1.
      Bales are stacked and tarped on the farm side. The transport of biomass from the
      farm side to a biorefinery takes place over a full year cycle, i.e. 365 days.
      Supply quantities range from 454 to 4540 dry tonnes/day (500-5000 dry tons/day).
      Delivered costs to a biorefinery with capacity of 1814 dry tonnes/day (2000 dry
      tons/day) are: 44-47 dollars/dry tonne for delivered bales (round and square); 37
      dollars/dry tonne for delivered loafs (size 2.4 m x 3.6 m x 6 m); 40 dollars/dry
      tonne for chopped biomass; and 48 dollars/dry tonne for ensiled chops. These
      costs do not include any payment to the farmers or switchgrass farming cost.
      Based on the data from literature, the switchgrass farming cost can range from 30
      to 36 dollars/dry tonne. These costs would be additional to the switchgrass
      collection and transportation cost. Switchgrass collection is generally less
      expensive than collection of straw or corn stover because of the assumed high
      yield of 11 dry tonnes/ha and a denser biomass. Energy consumption for delivery
      systems at this capacity ranges from 4.8% to 6.3% of the energy content of
      switchgrass. Additional 1% of the energy content of switchgrass is consumed in
      its farming. At 1814 dry tonnes/day (2000 dry tons/day) capacity, greenhouse gas
      emissions ranges from 75 to 100 kg of CO2/dry tonne of switchgrass delivered.

PMID- 16797979
TI  - Usability of size-excluded fractions of soy protein hydrolysates for growth and
      viability of Chinese hamster ovary cells in protein-free suspension culture.
AB  - To investigate the effect of size-excluded fraction of non-animal protein
      hydrolysate on growth, viability and longevity of Chinese hamster ovary (CHO)
      cells, several commercially available protein hydrolysates were evaluated as a
      feed supplement to chemically-defined protein-free suspension culture. Soy
      protein hydrolysates showed better supporting capability for cell growth and
      viability than the other types of hydrolysates. Maximal cell growth was not
      affected greatly by size exclusion of some soy hydrolysates such as bacto soytone
      and soy hydrolysates. CHO cells supplemented with size-excluded fractions of the
      two hydrolysates showed viable cell density and viability almost equal to those
      with their crude hydrolysates, although soy hydrolysates showed a little better
      performance. This suggested that the size-excluded hydrolysate fractions of some
      soy hydrolysate might be a potential culture medium additive to achieve better
      downstream operation in a large-scale production as well as enhanced
      productivity.

PMID- 16797980
TI  - Acrolein synthesis from glycerol in hot-compressed water.
AB  - Glycerol conversion was conducted in hot-compressed water (HCW: 573-673 K, 25
      34.5 MPa) using a batch and a flow apparatus and the influences of temperature,
      H(2)SO(4), glycerol concentration, and pressure, were examined. The yield of
      acrolein was enhanced by higher glycerol and H(2)SO(4) concentration, and higher
      pressure. Approximately 80% selectivity of acrolein was obtained at 90% of
      glycerol conversion with an acid catalyst in supercritical condition (673 K and
      34.5 MPa). The rate constant of acrolein decomposition was always higher than
      that of acrolein formation in the absence of acid catalyst but the rate constant
      of acrolein formation could be overcome that of acrolein decomposition by
      addition acid in supercritical condition.

PMID- 16797981
TI  - Removal of disperse dyes from textile wastewater using bio-sludge.
AB  - Granular activated carbon (GAC) did not show any significant adsorption ability
      on the disperse dyes, while resting (living) bio-sludge of a domestic wastewater
      treatment plant showed high adsorption abilities on both disperse dyes and
      organic matter. The dye adsorption ability of bio-sludge increased by
      approximately 30% through acclimatization with disperse dyes, and it decreased by
      autoclaving. The deteriorated bio-sludge could be reused after being washed with
      0.1N NaOH solution. Disperse Red 60 was more easily adsorbed onto the bio-sludge
      than Disperse Blue 60. The Disperse Red 60, COD, and BOD5 adsorption capacities
      of acclimatized, resting bio-sludge were 40.0+/-0.1, 450+/-12, and 300+/-10mg/g
      of bio-sludge, respectively. The GAC-SBR system could be applied to treat textile
      wastewater (TWW) containing disperse dyes with high dye, BOD5, COD, and TKN
      removal efficiencies of 93.0+/-1.1%, 88.0+/-3.1%, 92.2+/-2.7% and 51.5+/-7.0%,
      respectively without any excess bio-sludge production under an organic loading of
      0.18 kg BOD5/m3-d. Furthermore, the removal efficiencies increased with the
      addition of glucose into the system. The dye, BOD5, COD, and TKN removal
      efficiencies of the GAC-SBR system with TWW containing 0.89 g/L glucose were
      94.6+/-0.7%, 94.4+/-0.6%, 94.4+/-0.8% and 59.3+/-8.5%, respectively, under an SRT
      of 67+/-0.4 days.

PMID- 16797982
TI  - Accuracy of radioanalytical procedures used to determine the biobased content of
      manufactured products.
AB  - Radiocarbon analyses were used to determine the "biobased content" of a variety
      of diverse samples. The theoretical biobased contents of those samples were
      compared to the biobased content values obtained by radiocarbon analyses. Results
      of this work indicated that the radiocarbon analyses provided accurate (within +/
      3%, absolute) biobased content values for the samples tested. It is not practical
      to examine the accuracy of the radiocarbon analyses for every possible type of
      sample matrix. However, based on analyses performed on various types of samples,
      every indication is that the analyses provide accurate and reliable results on
      the biobased content of liquid and solid materials.

PMID- 16797983
TI  - Hepatoprotective activity of Schouwia thebica webb.
AB  - Oral administration of alcoholic extracts of Schouwia thebica Webb showed that
      extracts are safe for human use. The studied extracts are considered safe, since
      they failed to induce death of mice in doses up to 4000 mg/kg body weight.
      Hepatoprotective activity was studied for the total alcoholic extracts. The total
      extract was fractionated in turn with diethyl ether, chloroform, ethyl acetate,
      and n-butanol, respectively. These extracts were tested for possible
      hepatoprotective activity. It was found that the ethyl acetate and n-butanol
      extracts of S. thebica Webb showed hepatoprotective activity. These extracts
      significantly reduced the increase in activities of ALT, AST, and GGT, and levels
      of glucose, triglycerides, and cholesterol in serum of CCl(4)-treated rats. The
      extracts showing activity were found to contain flavonoids; one new compound,
      chrysoeriol-7-O-xylosoide- (1,2)-arabinofuranoside (2), in addition to another
      known four compound chrysoeriol (1), quercetin (3), quercetin-7-O-rhamnoside (4),
      and kaempferol-3-O-beta-D-glucoside (5). The isolated new compound was mainly
      found to be responsible for this activity when tested on animals in the
      laboratory. The structures were established by melting point, UV spectroscopy, EI
      Mass, Fab-Mass, and 1D and 2D NMR spectroscopic techniques on a 600MHz
      instrument.

PMID- 16797984
TI  - Synthesis, biochemical evaluation and rationalisation of the inhibitory activity
      of a series of 4-hydroxyphenyl ketones as potential inhibitors of 17beta
      hydroxysteroid dehydrogenase type 3 (17beta-HSD3).
AB  - We report the preliminary results of the synthesis and biochemical evaluation of
      a number of 4-hydroxyphenyl ketones as inhibitors of the isozyme of the enzyme
      17beta-hydroxysteroid dehydrogenase (17beta-HSD) responsible for the conversion
      of androstenedione (AD) to testosterone (T), more specifically type 3 (17beta
      HSD3). The results of our study suggest that we have synthesised compounds which
      are, in general, potent inhibitors of 17beta-HSD3, in particular, we discovered
      that 1-(4-hydroxy-phenyl)-nonan-1-one (8) was the most potent (IC(50) = 2.86 +/-
      0.03 microM). We have therefore provided good lead compounds in the synthesis of
      novel non-steroidal inhibitors of 17beta-HSD3.

PMID- 16797985
TI  - Studies towards the conception of new selective PPARbeta/delta ligands.
AB  - In order to define new PPARbeta/delta ligands, SAR study on the selective
      PPARbeta/delta activator L-165,041 led to the identification of one key
      functional group for selective PPARbeta/delta activation. Furthermore, taking
      advantage of SAR studies done elsewhere on the most selective PPARbeta/delta
      ligand GW501516, the conception of new ligands showing good affinity for
      PPARbeta/delta is reported. Finally, synthesis and biological evaluation of
      pyridine analogues have shown the benefical effect of the pyridine ring on the
      PPARbeta/delta subtype selectivity.

PMID- 16797986
TI  - Dual-acting agents that possess free radical scavenging and antithrombotic
      activities: design, synthesis, and evaluation of phenolic tetrahydro-beta
      carboline RGD peptide conjugates.
AB  - A new approach to construct a single dual-acting agent is described. Compounds 6a
      c are potent free radical scavengers as demonstrated by the EC(50) values in PC12
      cell survival assay in term of NO, H(2)O(2), and ()OH scavenging activity. The
      Ach-induced vaso-relaxation assay further confirms the potent NO scavenging
      activity of compounds 6a-c. In addition, 6a-c are efficacious in a rat arterial
      thrombosis, and are active in ADP- or PAF-induced in vitro platelet aggregation
      assay, suggesting that compounds 6a-c also possess anti-thrombotic activities.
      Since both free radical and thrombogenesis are important risk factors in
      myocardial ischemic/reperfusion injuries, these dual-acting agents having both
      free radical scavenging and antithrombolic activities may potentially be
      beneficial toward their treatment.

PMID- 16797987
TI  - Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D
      inhibitors.
AB  - Gallic acid, one of the most abundant plant phenolic acids, has been modified to
      cathepsin D protease inhibitors. The strategy of modification was proposed basing
      on some previously reported structure and activity relationship (SAR) studies.
      The synthesized naphthophenone fatty acid amide derivatives have been evaluated
      for in vitro cathepsin D inhibition activity. Two of them have shown significant
      inhibition activity with IC(50) values of 0.06 and 0.14 microM, respectively, as
      compared against pepstatin (0.0023 microM), the most potent inhibitor known so
      far. The study revealed that such attempts on gallic acid based pharmacophores
      might result in potent inhibitors of cathepsin D.

PMID- 16797988
TI  - Synthesis of a red-shifted fluorescence polarization probe for Hsp90.
AB  - The synthesis of a red-shifted cy3B-GM ligand and its evaluation as a
      fluorescence polarization probe for Hsp90 is presented.

PMID- 16797989
TI  - Resection of thoracic dumbbell neurinomas: single postero-lateral approach or
      combined posterior and transthoracic approach?
AB  - Dumbbell tumours are those with an intraspinal and a paraspinal component,
      connected through a frequently enlarged and eroded intervertebral foramen. Most
      dumbbell tumours are located in the thoracic spine, and most of them are
      schwannomas. The extraspinal tumour extension is usually larger than the
      intraspinal tumour part, but the intraspinal tumour component commonly causes the
      typical symptoms: local pain and symptoms from spinal cord compression in the
      thoracic spine. Diagnosis is best established by magnetic resonance imaging with
      and without contrast agent injection. Controversy exists as to whether to remove
      thoracic dumbbell tumours using a single posterior approach with posterolateral
      extension or using a combined posterior and transthoracic approach. We report the
      removal of a dumbbell neurinoma at T6/7 using a single posterior midline approach
      with laminectomy and costo-transversectomy and review the literature regarding
      the approaches to thoracic dumbbell tumours.

PMID- 16797990
TI  - Surgical technique and outcome in cervical and thoracic myelomeningocoele
      surgery.
AB  - Cervical and thoracic myelomeningocoeles differ from common lumbosacral
      myelomeningocoeles in many respects. We review the surgical technique and outcome
      achieved for a series of six infants who underwent surgery for cervical or
      thoracic myelomeningocoele. Five patients, who had intradural exploration and
      microsurgical untethering of the spinal cord, were neurologically stable on
      follow-up. The other patient, who had a simple subcutaneous resection of the sac
      without release of the intradural tethering bands, was re-operated on 16 months
      later, with progressive neurological symptoms due to cord tethering. Following re
      exploration and microsurgical untethering of the spinal cord, the neurological
      deficits significantly improved. We suggest that the surgical technique in these
      lesions should include careful intradural exploration and microsurgical release
      of the spinal cord by meticulous resection of all tethering bands. This enables
      postoperative neurological improvement and possible prevention of future
      neurological deficits due to cord tethering.

PMID- 16797991
TI  - A comparison of health-care costs involved in treating people with and without
      Parkinson's disease in Southern Sydney, New South Wales, Australia.
AB  - Twelve community-dwelling subjects with Parkinson's disease (PD) and 12 age
      matched healthy controls completed a 3-month diary of health-care utilisation in
      Sydney, Australia. The mean age for the PD group was 71.3 years (SD 5.9, range 62
      82 years) versus 73.2 years (SD 6.7, range 63-83 years) for the control group.
      The mean disease duration of the PD group was 6.8 years (SD 3.6, range 2-14
      years). The median Hoehn and Yahr stage was 3 (range 1-3). The mean 3-month total
      (both related and 'unrelated' to PD) health-care cost for the PD group was
      significantly higher than that for the 'healthy' control group (1,755 Australian
      dollars, SD 1,201 versus 413 Australian dollars, SD 515, P=0.001). Medication was
      the most costly component for both groups (PD 636 Australian dollars, SD 226
      versus controls 175 Australian dollars, SD 233, P<0.001) followed by general
      practitioner or specialist medical expenses (PD 564 Australian dollars, SD 670
      versus controls 205 Australian dollars, SD 397, p=0.12) and allied health-care
      costs (PD 323 Australian dollars, SD 178 versus controls 21 Australian dollars,
      SD 43, p<0.001). In the PD subgroup, the health-care costs attributed to PD
      during the 3-month period were significantly higher than health-care costs
      'unrelated' to PD (1,202 Australian dollars, SD 820 versus 553 Australian
      dollars, SD 591, p=0.03). On subgroup analysis, allied health-care costs (related
      to PD) achieved statistical significance (304 Australian dollars, SD 180 versus
      19 Australian dollars, SD 19, p<0.0001), whereas medication and general
      practitioner or specialist costs did not. In conclusion, we found that the total
      direct health-care cost of PD for patients with Hoehn and Yahr stage 3 was four
      times that of age- and sex-matched 'healthy' controls. The estimated annual cost
      (7,020 Australian dollars per patient) in our patient cohort was comparable to
      that reported in the United States and Europe.

PMID- 16797993
TI  - Lumbar juxta-facet cyst after trauma.
AB  - We report a post-traumatic lumbar facet cyst in which results of magnetic
      resonance imaging (MRI) performed at the time of injury were available. The
      patient was a 59-year-old man who presented with severe low back and right leg
      pain immediately after injury of his sacroiliac region in a traffic accident. MRI
      at the time of injury revealed high intensity signal change in the right facet
      joint at L4/5. Re-examination 5 months after the injury with MRI revealed a cyst,
      which was continuous with the facet joint. Surgical resection of the cyst yielded
      satisfactory results. We describe detailed MRI findings for this case and review
      the literature on traumatic juxta-facet cyst in the lumbar spine.

PMID- 16797994
TI  - Mobile vs. fixed bearing unicondylar knee arthroplasty: A randomized study on
      short term clinical outcomes and knee kinematics.
AB  - The literature contains limited yet controversial information regarding whether a
      fixed or a mobile bearing implant should be used in unicompartmental knee
      arthroplasty (UKA). This randomized study was to further document the performance
      and comparison of the two designs. Fifty-six knees in 48 patients (mean age of 72
      years) undergoing medial UKA were randomized into a fixed bearing
      (Miller/Galante) or a mobile bearing (Oxford) UKA. The 2 year clinical outcomes
      (clinical scores), radiographic findings, and weight bearing knee kinematics
      (assessed using RSA) were compared between the two groups. The mobile bearing
      knees displayed a larger and an incrementally increased tibial internal rotation
      (4.3 degrees, 7.6 degrees, 9.5 degrees vs. 3.0 degrees, 3.0 degrees, 4.2 degrees
      respectively at 30 degrees, 60 degrees, 90 degrees of knee flexion) compared to
      the fixed ones. The medial femoral condyle in the mobile bearing knees remained 2
      mm from the initial position vs. a 4.2 mm anterior translation in the fixed
      bearing knees during knee flexion. The contact point in the mobile bearing
      implant moved 2 mm posteriorly vs. a 6 mm anterior movement in the other group.
      The mobile bearing knees had a lower incidence of radiolucency at the bone
      implant interface (8% vs. 37%, p < 0.05). The incidence of lateral compartment OA
      and progression of OA at patello-femoral joint were equal. No differences were
      found regarding Knee Society Scores, WOMAC, and SF-36 scores (p > 0.05). This
      study indicates that mobile bearing knees had a better kinematics, a lower
      incidence of radiolucency but not yet a better knee function at 2 years.

PMID- 16797995
TI  - Changes in knee motion over the first 3 years with a mobile-bearing prosthesis.
AB  - The present work aims to evaluate the mobility of the polyethylene bearing in 25
      patients implanted with a mobile-bearing PCL-retaining TKR (Interax ISA, Striker
      Howmedica) under in vivo, weight-bearing conditions over 3 years' follow-up. We
      compared the bearing motion in response to specific tests in two consecutive
      follow-ups with Roentgen Stereophotogrammetric Analysis (RSA). Results showed
      that polyethylene continued to displace on the tibial baseplate over time:
      longitudinal rotations and medio-lateral translations tended to increase at the
      second follow-up (mean increases 0.7+/-2.5 degrees and 0.34+/-1.08 mm,
      respectively), while sagittal translations did not show any relevant change.
      Longitudinal rotations and AP translations were preserved when present at both
      follow-ups. Nevertheless, no statistical evidence of repeatable pattern of motion
      was found, since bearings frequently reversed their pattern of motion between the
      two follow-ups. The unconstrained polyethylene mobility resulted in an
      unrepeatable, erratic pattern of bearing motion intra-patient and over time. The
      changes in knee motion were found not to affect the clinical results over the
      first 3 years of follow-up. As in a fixed-bearing design, mobile-bearing design
      was not able to reproduce normal knee kinematics.

PMID- 16797996
TI  - Search for alpha-glucosidase inhibitors: new N-substituted valienamine and
      conduramine F-1 derivatives.
AB  - A solid-phase synthesis of new N-substituted valienamines has been developed and
      new synthesis of (+/-)-conduramine F-1, (-)-conduramine F-1, and (+)-ent
      conduramine F-1 is presented, together with the preparation of N-benzylated
      conduramines F-1. N-Benzylation of both valienamine and (+)-ent-conduramine F-1
      improves their inhibitory activity toward alpha-glucosidases significantly. The
      additional hydroxymethyl group makes valienamine derivatives more active than
      their (+)-ent-conduramine F-1 analogues.

PMID- 16797998
TI  - Structures of new amphidinols with truncated polyhydroxyl chain and their
      membrane-permeabilizing activities.
AB  - Two new homologues of amphidinols (AM14 and AM15) were isolated from the cultured
      dinoflagellate Amphidinium klebsii. The structures were elucidated on the basis
      of 2D NMR and collision-induced dissociation MS/MS and turned out to be closely
      related homologues of AM7. Their weak membrane-disrupting activity indicates that
      the hydrophobic polyene chain is essential for the potent biological activities.
      Structure-activity relationship for the polyhydroxyl part was then examined with
      use of AM homologues possessing various chain lengths, indicating that the pore
      size of the channel/lesion formed by AMs was not greatly affected by the length
      of the polyhydroxyl chain.

PMID- 16797997
TI  - Synthesis and pharmacological studies of new hybrid derivatives of fentanyl
      active at the mu-opioid receptor and I2-imidazoline binding sites.
AB  - Two series of fentanyl-derived hybrid molecules bearing potent I2-imidazoline
      binding site (IBS) ligands (i.e., guanidine and BU224 moieties) linked with an
      aliphatic (m=2, 3, 4, 6, 7, 8, 9 and 12 methylene units) or aromatic spacer were
      prepared. Their affinities for the mu-opioid receptors and for the I2-IBS were
      determined through competition binding studies on human postmortem brain
      membranes. Whereas the BU224 hybrid molecules bound to the mu-opioid receptor and
      the I2-IBS in the micromolar to low micromolar range, the alkaneguanidine series
      exhibited remarkable affinities in the nanomolar range for both receptors.
      [35S]GTPgammaS functional assays were performed on human postmortem brain
      membranes with selected ligands from each series (4f and 8g) showing the highest
      dual affinity for the mu-opioid receptor and I2-IBS affinities. Both compounds
      displayed agonist properties: at the mu-opioid receptor for the alkaneguanidine
      derivative 4f (spacer: six methylene units) and at a G-protein coupled receptor
      (GPCR) which remains to be determined for 8g. The lack of analgesic properties of
      4f in vivo (i.e., hot plate and writhing tests in mice), discordant with the good
      in vitro binding data (Ki mu=1.04+/-0.28 nM, Ki I2=409+/-238 nM), may possibly be
      due to the low intrinsic efficacy of the compound. Alternatively, a low access to
      the central nervous system for this kind of hybrid molecules cannot be ruled out.
      Two new compounds reported here (9f and 13), which were not dual acting, are
      worth mentioning for their outstanding binding affinities; 9f bound to the mu
      opioid receptor with a picomolar affinity (Ki=0.0098+/-0.0033 nM), whereas 13
      presented an I2-IBS affinity (Ki=18+/-11 nM) similar to the reference compound
      BU224.

PMID- 16797999
TI  - Role of small bioorganic molecules in stem cell differentiation to insulin
      producing cells.
AB  - The use of small specific molecules has been instrumental in the modulation of
      stem cell proliferation and differentiation to obtain insulin-containing cells.
      Examples include nutrients (glucose, nicotinamide and retinoic acid), acids
      (butyrate), alkaloids (cyclopamine and conophylline) and pharmacological agents
      (LY294002 and wortmannin). These molecules, alone or in combination with specific
      growth factors and hormones, will likely provide key information to design
      specific culture media in order to obtain customized cells for implantation in
      diabetes. In addition, the study of such molecules will help to understand the
      mechanisms involved in stem cell biology as well as contribute to the design of
      specific drugs for islet repair and regeneration in diabetes.

PMID- 16798000
TI  - Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone
      and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking
      cessation agents.
AB  - A codrug approach for simultaneous treatment of alcohol abuse and tobacco
      dependence is considered as very desirable because of substantial evidence that
      smoking is increased significantly during drinking, and that smoking is regarded
      as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study
      was to design and synthesize codrugs for simultaneous treatment of alcohol abuse
      and tobacco dependence. Two novel tripartate codrugs of naltrexone (NTX) and
      naltrexol (NTXOL) covalently linked to hydroxybupropion (BUPOH) were synthesized
      (25 and 26, respectively), and their hydrolytic cleavage to the parent drugs was
      determined. These codrugs were generally less crystalline when compared to NTX,
      or NTXOL, as indicated by their lower melting points, and were expected to be
      more lipid-soluble. Also, the calculated clogP values were found to be higher for
      the codrugs compared to those for NTX and NTXOL. The studies on the hydrolysis of
      the codrugs provided good evidence that they could be efficiently converted to
      the parent drugs in buffer at physiological pH. Thus, these codrugs are likely to
      be cleaved enzymatically in vivo to generate the parent drugs, and are considered
      to be potential candidates for simultaneous treatment of alcohol abuse and
      tobacco dependence.

PMID- 16798001
TI  - Comparative uptake, metabolism, and utilization of menaquinone-4 and
      phylloquinone in human cultured cell lines.
AB  - It is generally accepted that the availability of vitamin K in vivo depends on
      its homologues, the biological activities of which would differ among organs. To
      test this hypothesis, we examined the uptake, metabolism, and utilization of
      menaquinone-4 (MK-4) and phylloquinone (PK) using 18O-labeled compounds in two
      cultured human cell lines (HepG2 and MG-63). Lipid extracts were prepared from
      the cells and media after 1, 3, and 6h of incubation. The detection of the
      vitamin K analogues (18O-, 16O-quinone, and epoxide forms) was carried out with
      LC-APCI-MS/MS as previously reported. The 18O of vitamin K was replaced with
      atmospheric 16O2 during the formation of vitamin K epoxide with a carboxylative
      catalytic reaction. As a result, a significant difference was observed between MK
      4 and PK in the amounts taken up into the cells. The 18O-labeled MK-4 was rapidly
      and remarkably well absorbed into the cells and metabolized to the epoxide form
      via a hydroquinone form as compared to the 18O-labeled PK. The difference in
      uptake of MK-4 and PK was not affected by treatment with warfarin although the
      metabolism of both compounds was markedly inhibited. This methodology should be
      utilized to clarify some of the actions of vitamin K in target cells and
      facilitate the development of new vitamin K drugs.

PMID- 16798003
TI  - Synthesis and DNA cleavage activities of mononuclear macrocyclic polyamine
      zinc(II), copper(II), cobalt(II) complexes which linked with uracil.
AB  - Mononuclear macrocyclic polyamine zinc(II), copper(II), cobalt(II) complexes,
      which could attach to peptide nucleic acid (PNA), were synthesized as DNA
      cleavage agents. The structures of these new mononuclear complexes were
      identified by MS and (1)H NMR spectroscopy. The catalytic activities on DNA
      cleavage of these mononuclear complexes with different central metals were
      subsequently studied, which showed that copper complex was better catalyst in the
      DNA cleavage process than zinc and cobalt complexes. The effects of reaction
      time, concentration of complexes were also investigated. The results indicated
      that the copper(II) complexes could catalyze the cleavage of supercoiled DNA (pUC
      19 plasmid DNA) (Form I) under physiological conditions to produce selectively
      nicked DNA (Form II, no Form III produced) with high yields. The mechanism of the
      cleavage process was also studied.

PMID- 16798002
TI  - Synthesis and biological evaluation of 1,3-diphenylprop-2-en-1-ones possessing a
      methanesulfonamido or an azido pharmacophore as cyclooxygenase-1/-2 inhibitors.
AB  - A group of (E)-1,3-diphenylprop-2-en-1-one derivatives (chalcones) possessing a
      MeSO(2)NH, or N(3), COX-2 pharmacophore at the para-position of the C-1 phenyl
      ring were synthesized using a facile stereoselective Claisen-Schmidt condensation
      reaction. In vitro COX-1/COX-2 structure-activity relationships were determined
      by varying the substituents on the C-3 phenyl ring (4-H, 4-Me, 4-F, and 4-OMe).
      Among the 1,3-diphenylprop-2-en-1-ones possessing a C-1 para-MeSO(2)NH COX-2
      pharmacophore, (E)-1-(4-methanesulfonamidophenyl)-3-(4-methylphenyl)prop-2-en-1
      one (7b) was identified as a selective COX-2 inhibitor (COX-2 IC(50)=1.0 microM;
      selectivity index >100) that was less potent than the reference drug rofecoxib
      (COX-2 IC(50)=0.50 microM; SI>200). The corresponding 1,3-diphenylprop-2-en-1-one
      analogue possessing a C-1 para-N(3) COX-2 pharmacophore, (E)-1-(4-azidophenyl)-3
      (4-methylphenyl)prop-2-en-1-one (7f), exhibited potent and selective COX-2
      inhibition (COX-1 IC(50)=22.2 microM; COX-2 IC(50)=0.3 microM; SI=60). A
      molecular modeling study where 7b and 7f were docked in the binding site of COX-2
      showed that the p-MeSO(2)NH and N(3) substituents on the C-1 phenyl ring are
      oriented in the vicinity of the COX-2 secondary pocket (His90, Arg513, Phe518,
      and Val523). The structure-activity data acquired indicate that the propenone
      moiety constitutes a suitable scaffold to design new acyclic 1,3-diphenylprop-2
      en-1-ones with selective COX-1 or COX-2 inhibitory activity.

PMID- 16798004
TI  - Analytical calculations of the solid angles subtended by a well-type detector at
      point and extended circular sources.
AB  - Knowledge of the solid angle (and consequently, the geometrical efficiency) is
      essential in all absolute measurements of the strengths of radioactive materials
      and to calibrate detectors. The method of high-efficiency gamma counting by means
      of well-type HPGe and NaI (Tl) detectors is widely used and has proved a powerful
      tool, particularly when low-activity, small-volume environmental samples are to
      be analyzed by gamma-ray spectrometry. In the present work, we introduce a direct
      analytical method for calculating the solid angle subtended by a well-type
      detector at axial point, non-axial point, extended circular disk and cylindrical
      sources. The validity of the derived analytical expressions was successfully
      confirmed by the comparisons with some published data (experimental and Monte
      Carlo).

PMID- 16798005
TI  - Cromolyn administration (to block mast cell degranulation) reduces necrosis of
      dystrophic muscle in mdx mice.
AB  - Duchenne muscular dystrophy is a lethal muscle wasting disorder, resulting from
      mutations in the gene encoding for the skeletal muscle protein dystrophin. The
      absence of functional dystrophin leaves the muscle membrane vulnerable to damage
      during contraction. Damage initially occurs as 'tears' in the membrane, this
      damage can be exacerbated by the inflammatory response leading to myofibre
      necrosis rather than repair. Mast cells resident within skeletal muscle represent
      an immediate source of pro-inflammatory cytokines. We hypothesise that blockade
      of mast cell degranulation would reduce the extent of myofibre necrosis in the
      mdx mouse. Daily cromolyn injections were performed on young and exercised adult
      mdx mice and histological analysis confirmed that mast cell degranulation
      contributes to myofibre necrosis. This research identified high biological
      variation between individual mdx mice in the severity of the dystrophic
      pathology, and supported a relationship between extent of muscle damage in adult
      mdx mice and their individual enthusiasm for voluntary wheel running.

PMID- 16798007
TI  - Quantitative study of fluorescence excitation and emission spectra of bean
      leaves.
AB  - A quantitative and comprehensive knowledge of leaf fluorescence is required for
      the interpretation of fluorescence signals at the canopy level and also for the
      modelling of leaf and canopy fluorescence. In this work we present full range
      fluorescence excitation and emission spectra of intact leaves, expressed in units
      of apparent spectral fluorescence yield, from both the adaxial and the abaxial
      sides of the leaves, and for both front-side and back-side geometries. Emission
      spectra were measured for incident radiations in the blue and the green spectral
      range. The red/far-red fluorescence ratio depended on the measurement geometry
      and on the excitation wavelength. Excitation spectra were measured for emissions
      at 687 and 760 nm. When the abaxial side was illuminated, the measured spectra
      always had a larger intensity compared to adaxial side that is explained by the
      higher scattering of the spongy tissues. At 760 nm, the spectra had the same
      shape for front-side and back-side geometry, indicating that scattering
      predominated. At 687 nm, the shape of the spectra was very different for front
      side and back-side geometry due to re-absorption of red fluorescence within the
      leaf. The comparison of excitation spectra measured from the adaxial or the
      abaxial side revealed differences in carotenoid absorption.

PMID- 16798006
TI  - Hearing loss and cochlear damage in experimental pneumococcal meningitis, with
      special reference to the role of neutrophil granulocytes.
AB  - Hearing loss is a well-known sequelae from meningitis, affecting up to 25% of
      survivors. However, the principal components of the infectious and inflammatory
      reaction responsible for the sensorineural hearing loss remain to be identified.
      The present study aimed to investigate the impact of an augmented neutrophil
      response on the development of hearing loss and cochlear damage in a model of
      experimental pneumococcal meningitis in rats. Hearing loss and cochlear damage
      were assessed by distortion product oto-acoustic emissions (DPOAE), auditory
      brainstem response (ABR) and histopathology in rats treated with ceftriaxone 28 h
      after infection. Rats were treated with Granulocyte Colony Stimulating Factor (G
      CSF) initiated prior to infection, 28 h after infection or with ceftriaxone only.
      Rats were followed for 7 days, and assessment of hearing was performed before
      infection and 24 h and day 8 after infection. Pretreatment with G-CSF increased
      hearing loss 24 h after infection and on day 8 compared to untreated rats (Mann
      Whitney, P = 0.012 and P = 0.013 respectively). The increased sensorineural
      hearing loss at day 8 was associated with significantly decreased spiral ganglion
      cell counts (P = 0.0006), increased damage to the organ of Corti (P = 0.007),
      increased areas of inflammatory infiltrates (P = 0.02) and increased white blood
      cell (WBC) counts in cerebrospinal fluid on day 8 after infection (P = 0.0084).
      Initiation of G-CSF 28 h after infection did not significantly affect hearing
      loss or cochlear pathology compared to controls. In conclusion, the inflammatory
      host reaction contributes significantly to the development of hearing loss in
      experimental meningitis.

PMID- 16798008
TI  - RETRACTED: Expression, purification, and characterization of human intestinal
      trefoil factor in Pichia pastoris.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see . The Publisher apologizes for any inconvenience this may
      cause.

PMID- 16798009
TI  - Expression and purification of functional human anthrax toxin receptor (ATR/TEM8)
      binding domain from Escherichia coli.
AB  - Anthrax is caused by the gram-positive, spore-forming bacterium, Bacillus
      anthracis. Anthrax receptors play a crucial role in the pathogenesis of the
      anthrax disease. Anthrax toxin receptor ATR/TEM8 VWA domain is responsible for
      the binding of protective antigen (PA) of B. anthracis, and thus an attractive
      target for structure-based drug therapies. However, the production of soluble and
      functional ATR/TEM8 VWA domain currently requires the use of mammalian expression
      systems. In this work, we expressed the ATR/TEM8 VWA domain as a fusion protein
      in Escherichia coli. Recombinant ATR/TEM8 VWA domain has been purified to
      homogeneity, and its identity has been verified by both N-terminal protein
      microsequencing and mass spectrometry. The purified ATR/TEM8 VWA domain exhibits
      very high affinity to PA based on BIAcore assay. Moreover, like the domain
      expressed in mammalian system, the bacterially expressed ATR/TEM8 VWA domain can
      block cytotoxicity induced by anthrax toxins, suggesting that the bacterially
      expressed ATR/TEM8 VWA domain is properly folded and fully functional.

PMID- 16798011
TI  - Methodological issues with the interpolated twitch technique.
AB  - A number of methodological issues in the use of the interpolated twitch technique
      were investigated for their effect on true maximum force (TMF) and activation
      (ACT): timing of control (pre- vs post-contraction) and superimposed twitches
      (first vs second); type of twitch stimulus (primarily magnitude); and the type of
      extrapolation utilised. On three occasions subjects performed a series of maximal
      and sub-maximal contractions of the knee extensors, with electrically evoked
      twitches delivered before, during and after each contraction. The twitch
      voluntary force relationship was concave for all types of twitch stimuli, and
      extrapolation using this relationship typically calculated TMF 39N (7%) higher,
      and ACT 7% lower than linear extrapolation. The timing of the control (2-4%) and
      superimposed twitches (approximately 4%) both influenced TMF and ACT. Despite the
      different twitch stimuli being a range of magnitudes (13-32% maximum voluntary
      force) they did not affect TMF and ACT. A novel finding was that prior
      potentiation changed the shape of the twitch-voluntary force relationship. For
      precise measurement of TMF and ACT it is recommended that: extrapolation is based
      on the twitch-voluntary force relationship of the experimental model; and post
      contraction potentiated twitches be used, as the superimposed twitch on a high
      level contraction appears to be potentiated.

PMID- 16798010
TI  - Incorporating a TEV cleavage site reduces the solubility of nine recombinant
      mouse proteins.
AB  - Failure to express soluble proteins in bacteria is mainly attributed to the
      properties of the target protein itself, as well as the choice of the vector, the
      purification tag and the linker between the tag and protein, and codon usage. The
      expression of proteins with fusion tags to facilitate subsequent purification
      steps is a widely used procedure in the production of recombinant proteins.
      However, the additional residues can affect the properties of the protein;
      therefore, it is often desirable to remove the tag after purification. This is
      usually done by engineering a cleavage site between the tag and the encoded
      protein that is recognised by a site-specific protease, such as the one from
      tobacco etch virus (TEV). In this study, we investigated the effect of four
      different tags on the bacterial expression and solubility of nine mouse proteins.
      Two of the four engineered constructs contained hexahistidine tags with either a
      long or short linker. The other two constructs contained a TEV cleavage site
      engineered into the linker region. Our data show that inclusion of the TEV
      recognition site directly downstream of the recombination site of the Invitrogen
      Gateway vector resulted in a loss of solubility of the nine mouse proteins. Our
      work suggests that one needs to be very careful when making modifications to
      expression vectors and combining different affinity and fusion tags and cleavage
      sites.

PMID- 16798013
TI  - Functional pathway-defined MRI diffusion measures reveal increased transverse
      diffusivity of water in multiple sclerosis.
AB  - The diffusion properties of water are sensitive to microscopic changes in the
      white matter of multiple sclerosis (MS) patients. Typical MRI measures of disease
      burden in MS demonstrate modest to poor correlation with disability. Functional
      MRI and DTI-based fiber tracking were used to define the interhemispheric white
      matter pathway connecting bilateral supplementary motor areas (SMA) in 16 MS
      patients sand 16 control subjects. Fractional anisotropy (FA), mean diffusivity
      (MD), longitudinal (lambda(1)) and transverse diffusivity (lambda(2)) were
      measured along this pathway in all subjects. Mean FA was 0.587 +/- 0.032 for
      patients and 0.608 +/- 0.020 for controls (P < 0.02). Mean MD was (0.821 +/-
      0.055) x 10(-3) mm(2) s(-1) for patients and (0.770 +/- 0.020) x 10(-3) mm(2) s(
      1) for controls (P < 0.004). Mean lambda(1) values were (1.462 +/- 0.099) x 10(
      3) mm(2) s(-1) for patients and (1.400 +/- 0.034) x 10(-3) mm(2) s(-1) for
      controls (P < 0.02). Mean lambda(2) values were (0.500 +/- 0.047) x 10(-3) mm(2)
      s(-1) for patients and (0.454 +/- 0.027) x 10(-3) mm(2) s(-1) for controls (P <
      0.001). In addition, the correlation between the Multiple Sclerosis Functional
      Composite (MSFC) and transverse diffusivity was -0.341 (P < 0.05). The component
      test of the MSFC most related to the SMA pathway studied with our MRI method
      (Nine-hole Peg Test) showed significant correlation with transverse diffusivity
      (r = 0.392, P < 0.02), indicating that probing functional pathways with MRI
      measures can lead to a better reflection of disease status.

PMID- 16798012
TI  - Dissociation between the cognitive process and the phenomenological experience of
      TOT: effect of the anxiolytic drug lorazepam on TOT states.
AB  - TOT states may be viewed as a temporary and reversible microamnesia. We
      investigated the effects of lorazepam on TOT states in response to general
      knowledge questions. The lorazepam participants produced more commission errors
      and more TOTs following commission errors than the placebo participants (although
      the rates did not change). The resolution of the TOTs was unimpaired by the drug.
      Neither feeling-of-knowing accuracy nor recognition were affected by lorazepam.
      The higher level of incorrect recalls produced by lorazepam participants may be
      due to the fact that they were more frequently temporarily unable to access a
      known item. For some of these items, the awareness of the retrieval failure
      resulted in a commission TOT (phenonemological TOT after a commission error). The
      resolution of the TOT conflict is discussed in the light of the anxiolytic and
      anticonflict effects of lorazepam. The data are discussed in terms of
      contemporary theories of TOTs and the effects that benzodiazepines have on
      semantic memory.

PMID- 16798014
TI  - Electrical brain imaging reveals spatio-temporal dynamics of timbre perception in
      humans.
AB  - Timbre is a major attribute of sound perception and a key feature for the
      identification of sound quality. Here, we present event-related brain potentials
      (ERPs) obtained from sixteen healthy individuals while they discriminated complex
      instrumental tones (piano, trumpet, and violin) or simple sine wave tones that
      lack the principal features of timbre. Data analysis yielded enhanced N1 and P2
      responses to instrumental tones relative to sine wave tones. Furthermore, we
      applied an electrical brain imaging approach using low-resolution electromagnetic
      tomography (LORETA) to estimate the neural sources of N1/P2 responses. Separate
      significance tests of instrumental vs. sine wave tones for N1 and P2 revealed
      distinct regions as principally governing timbre perception. In an initial stage
      (N1), timbre perception recruits left and right (peri-)auditory fields with an
      activity maximum over the right posterior Sylvian fissure (SF) and the posterior
      cingulate (PCC) territory. In the subsequent stage (P2), we uncovered enhanced
      activity in the vicinity of the entire cingulate gyrus. The involvement of extra
      auditory areas in timbre perception may imply the presence of a highly
      associative processing level which might be generally related to musical
      sensations and integrates widespread medial areas of the human cortex. In
      summary, our results demonstrate spatio-temporally distinct stages in timbre
      perception which not only involve bilateral parts of the peri-auditory cortex but
      also medially situated regions of the human brain associated with emotional and
      auditory imagery functions.

PMID- 16798015
TI  - fMRI investigation of cortical and subcortical networks in the learning of
      abstract and effector-specific representations of motor sequences.
AB  - A visuo-motor sequence can be learned as a series of visuo-spatial cues or as a
      sequence of effector movements. Earlier imaging studies have revealed that a
      network of brain areas is activated in the course of motor sequence learning.
      However, these studies do not address the question of the type of representation
      being established at various stages of visuo-motor sequence learning. In an
      earlier behavioral study, we demonstrated that acquisition of visuo-spatial
      sequence representation enables rapid learning in the early stage and progressive
      establishment of somato-motor representation helps speedier execution by the late
      stage. We conducted functional magnetic resonance imaging (fMRI) experiments
      wherein subjects learned and practiced the same sequence alternately in normal
      and rotated settings. In one rotated setting (visual), subjects learned a new
      motor sequence in response to an identical sequence of visual cues as in normal.
      In another rotated setting (motor), the display sequence was altered as compared
      to normal, but the same sequence of effector movements was used to perform the
      sequence. Comparison of different rotated settings revealed analogous transitions
      both in the cortical and subcortical sites during visuo-motor sequence learning-a
      transition of activity from parietal to parietal-premotor and then to premotor
      cortex and a concomitant shift was observed from anterior putamen to a combined
      activity in both anterior and posterior putamen and finally to posterior putamen.
      These results suggest a putative role for engagement of different cortical and
      subcortical networks at various stages of learning in supporting distinct
      sequence representations.

PMID- 16798016
TI  - Impaired self-awareness and theory of mind: an fMRI study of mentalizing in
      alexithymia.
AB  - Alexithymic individuals have difficulty in recognizing and describing emotions in
      themselves. We investigated the neuronal basis of mentalizing in alexithymia to
      determine whether there is a common neuronal substrate associated with knowing
      the mental states of the self and others. Individuals high in alexithymia (n =
      16) and low in alexithymia (n = 14) were selected from a pool of 310 college
      students using a combination of the Toronto Alexithymia Scale (TAS-20) and the
      Structured Interview version of the Beth Israel Questionnaire (SIBIQ). We
      compared the two groups on psychological measures, including ratings of
      mentalizing and the Interpersonal Reactivity Index (IRI), and regional brain
      activation using functional magnetic resonance imaging (fMRI) during a
      mentalizing animation task. The results for both groups showed activation in
      regions associated with mentalizing: medial prefrontal cortices (MPFC), temporo
      parietal junctions (TPJ), and the temporal pole (TP). Alexithymics had lower
      mentalizing and IRI perspective-taking scores and less activation in the right
      MPFC. Activity in the MPFC was positively correlated with the mentalizing score
      and the IRI perspective-taking score. Although there were no group differences in
      cerebral activity in the TPJ and the TP, the activity in the right TP had a
      positive correlation with mentalizing and IRI personal distress scores. These
      results suggest that alexithymic individuals have an impairment in mentalizing
      associated with an inability to take the perspective of others. Thus, the skills
      involved in comprehending the self and others are inter-related and play an
      important role in emotion regulation.

PMID- 16798017
TI  - Functional significance of age-related differences in motor activation patterns.
AB  - Recent functional MRI (fMRI) studies have revealed an increased task-related
      activation in older subjects during a variety of cognitive or perceptual tasks,
      which may signal beneficial compensatory activity to counteract structural and
      neurochemical changes associated with aging. Under the assumption that
      incremental movement rates are associated with an increased functional demand on
      the motor system, we used fMRI and acoustically paced movements of the right
      index finger at six different frequencies (2.0, 2.5, 3.0, 4.0, 5.0 and 6.0 Hz) to
      investigate the behavioral significance of additionally recruited brain regions
      in a group of healthy, older subjects (mean age 66 +/- 8 years) compared with a
      group of young (mean age 23 +/- 7 years) subjects. The actual tapping frequency
      (F(1,14) = 0.049, P = 0.829), the tapping interval (F(1,14) = 0.043, P = 0.847),
      and the error rates (F(1,14) = 0.058, P = 0.743) did not differ significantly
      between both groups, whereas there was a significant increase in reaction time in
      the older subjects (F(1,14) = 281.786, P < or = 0.001). At all frequencies, the
      older subjects demonstrated significant overactivation within the ipsilateral
      sensorimotor and premotor cortex. However, we did not observe an increased age
      related overactivation during higher movements rates in these or other motor
      regions. Moreover, the magnitude of the hemodynamic response in overactivated
      regions remained constant across all frequencies. In contrast to cognitive tasks,
      these findings indicate that an age-related overactivation within the motor
      system is not related to the functional demand and does not necessarily reflect
      reorganization to compensate for the neurobiological changes of aging.

PMID- 16798018
TI  - Slab-like functional architecture of higher order cortical area 21a showing
      oblique effect of orientation preference in the cat.
AB  - Optical imaging based on intrinsic signals is a powerful tool for in vivo
      studying functional organization of various cortices. Here, the functional
      architecture of orientation-sensitive neurons in higher order extrastriate
      cortical area 21a was investigated in cats using optical imaging combined with
      electrophysiological methods. It is found that neurons in area 21 with similar
      preferred orientations were functionally organized into a slab-like columnar
      structure orthogonal to the cortical surface, and the orientation columns were
      distributed more densely than those in area 17. The responsiveness and activated
      areas of optical maps visually elicited by the horizontal and vertical gratings
      were always larger than those by oblique gratings in areas 21a and 17. This
      neural oblique effect shown in orientation maps was more significant in area 21a
      than that in area 17. The findings suggest a neuronal mechanism in the higher
      order extrastriate cortex involving the visual perceptive process of the
      superiority of cardinal contours.

PMID- 16798019
TI  - Phylogeny and biogeography of ice crawlers (Insecta: Grylloblattodea) based on
      six molecular loci: designating conservation status for Grylloblattodea species.
AB  - Ice crawlers (Insecta: Grylloblattodea) are rarely encountered insects that
      consist of five genera representing 26 species from North America and Asia. Asian
      grylloblattids are the most diverse, but North American ice crawlers (genus
      Grylloblatta) are known for their adaptation to cold conditions. Phylogenetic
      relationships among grylloblattid species and genera are not known. Six genes
      were sampled in 35 individuals for 18S rRNA, 28S rRNA, histone 3, 12S rRNA, 16S
      rRNA, and cytochrome oxidase II from 21 populations of Grylloblatta, three
      populations from Japan (genus Galloisiana), and three populations from Russia
      (genus Grylloblattina). Phylogenetic analysis of these data with two mantophasmid
      outgroups in POY supported monophyletic genera, with Grylloblatta as sister to
      Grylloblattina. Grylloblatta was shown to contain two major lineages: a clade in
      Northern California and Oregon and a clade in Washington and Oregon. One new
      species and six candidate species are proposed. IUCN Red List Conservation
      Criteria were implemented to designate conservation status for each lineage.

PMID- 16798020
TI  - Factors predicting seizure outcome of anterior temporal lobectomy for patients
      with mesial temporal sclerosis.
AB  - PURPOSE: To investigate the factors, including those associated with ictal scalp
      EEG results, related to surgical outcome in patients with pathologically proven
      mesial temporal sclerosis. METHODS: We studied 51 consecutive patients who
      underwent anterior temporal lobectomy and had at least 4 years of follow-up.
      Surgical outcome was classified as being seizure-free or not seizure-free during
      the first two and the subsequent two postoperative years. Clinical variables and
      scalp EEG parameters were subjected to statistical analysis. RESULTS: Of the 51
      patients, 36 (70.6%) were seizure-free during postoperative years 3 and 4.
      Logistic regression analysis revealed that seizure remission for the first 2
      years (p = 0.002) and contralateral propagated ictal discharges (p = 0.015) were
      independently related to seizure outcome at 4 years. Patients who were seizure
      free at 2 years had an 86.5% chance of remaining seizure-free at 4 years. Of the
      patients without bitemporal asynchrony or switch of lateralization, 88.9% were
      seizure free at 4 years, compared with 54.5% of patients with asynchrony or
      switch of lateralization (p = 0.007). These two factors, however, were not
      predictive of seizure outcome at 2 years. CONCLUSIONS: Contralateral propagated
      ictal discharges, including bitemporal asynchrony and switch of lateralization,
      unfavorably influence long-term seizure outcome. Long-term seizure control is
      best when the patient has no such propagation patterns of ictal discharges and is
      seizure-free during the first 2 years after temporal lobectomy.

PMID- 16798021
TI  - Cerebral arrhythmia influencing cardiac rhythm: a case of ictal bradycardia.
AB  - Partial seizures of temporal origin can be associated with clinically significant
      tachycardia or bradycardia. Ictal bradycardia and asystole has been implicated in
      the etiology of sudden unexpected death in epileptic patients (SUDEP). Although
      symptomatic ictal bradycardia has been relatively well described in the
      literature; information on asymptomatic ictal bradycardia is scarce. We report a
      case of asymptomatic ictal bradycardia diagnosed during video EEG telemetry that
      was subsequently implanted with a cardiac pacemaker.

PMID- 16798022
TI  - Acute effect of beta amyloid on synchronized spontaneous Ca2+ oscillations in
      cultured hippocampal networks.
AB  - The effects of beta amyloid (Abeta) on cytoplasmic Ca(2+) ([Ca(2+)](c)) have been
      studied extensively, but the current literature on this aspect is confusing. We
      reported that 20 microM Abeta(25-35) significantly inhibited the synchronized
      spontaneous cytoplasmic Ca(2+) transients immediately after application, whereas
      it had little effect on the baseline [Ca(2+)](c) concentration in neurons.
      Abeta(1-42) had a similar effect on the Ca(2+) transients as Abeta(25-35), while
      it increased baseline [Ca(2+)](c) concentration gradually. However, Abeta(1-40)
      had little effect on either Ca(2+) transients or baseline [Ca(2+)](c). Such
      differential effects of Abeta on Ca(2+) signals might explain, at least
      partially, the confusing observations from the previous studies and provide
      important therapeutic implications for preventing or reversing early neuron
      damage in Alzheimer's disease.

PMID- 16798023
TI  - Mechano-chemical signaling in F9 cells.
AB  - We investigated the molecular mechanism by which cells recognize and respond to
      physical forces in their local environment. Using a model system, to study wild
      type mouse F9 embryonic carcinoma cells, we examined how these cells sense
      mechanical stresses and translate them into biochemical responses through their
      cell surface receptor integrin and via the focal adhesion complex (FAC). Based on
      studies that show that many signal transducing molecules are immobilized on the
      cytoskeleton at the site of integrin binding within the focal adhesion complex,
      we found a time-dependent increase of focal adhesion kinase (pp125(FAK))
      phosphorylation possibly due to protein kinase C (PKC) activation as well as
      protein kinase A (PKA) activity increase upon cell adhesion/spreading. These
      studies provide some insight into intracellular mechano-chemical signaling.

PMID- 16798024
TI  - Studying cellular architecture in three dimensions with improved resolution: Ta
      replicas revisited.
AB  - Metal replicas have been used for surface analysis of biological structures with
      a variety of spatial resolutions. Platinum (Pt) has been the metal of choice
      because it provides very stable replicas and images of high contrast. Some other
      metals, such as tantalum (Ta) have been reported to provide better resolution on
      isolated macromolecular complexes and cellular structures. Our goal is to study
      the gain in detail with Ta and to evaluate if it provides enough detail and
      resolution to assist in the study of complex volumes of intact cellular
      structures obtained by methods that reach molecular resolution. To this purpose
      Pt and Ta replicas of cellular structures and viruses have been studied by
      transmission electron microscopy (TEM). Replicas of Ta show new details on the
      surface of two types of isolated viral particles such as 100 nm bunyaviruses and
      large, > 300 nm, vaccinia virus (VV). Inside cells, the structural pieces that
      build VV immature particles are visualized only in Ta replicas. Looking for
      smaller intracellular complexes, new details are also seen in nuclear pores from
      Ta replicas. Additional masses, most likely representing the cargo during
      transport, are distinguished in some of the pores. Visualization of proteins in
      plasma membranes strongly suggests that detail and resolution of Ta replicas are
      similar to those estimated for 3D maps currently obtained by electron tomography
      of viruses and cells.

PMID- 16798025
TI  - An "all-comers" venous duplex scan policy for patients with lower limb varicose
      veins attending a one-stop vascular clinic: is it justified?
AB  - OBJECTIVE: To determine whether clinical assessment could predict the correct
      management of patients with varicose veins (VVs), select those who would need
      duplex scanning, and identify deep venous reflux (DVR). METHODS: Prospective
      study of 342 consecutive limbs with VVs. These were divided into 3 groups: 170
      (50%) limbs with primary VVs without skin changes (group I), 37 (11%) with
      recurrent VVs without skin changes (group II), and 135 (39%) with primary or
      recurrent VVs with skin changes (group III). Clinicians were asked to document
      whether they would normally request a duplex scan because of clinical
      uncertainty. Agreement between decision-making based on clinical and on duplex
      findings was documented. RESULTS: Agreement between clinical and duplex findings
      for groups I, II, and III was 82%, 59%, and 67%, respectively. In 112 cases (66%)
      in group I, clinicians felt certain about the diagnosis and yet duplex scanning
      revealed they were wrong in 12% of cases. In group II, clinicians would request a
      duplex scan because of clinical uncertainty in 30 (81%) cases. In group III, the
      sensitivity, specificity, positive and negative predictive value of clinical
      assessment in detecting DVR was 32%, 77%, 24%, and 83%, respectively.
      CONCLUSIONS: Clinical evaluation of patients with VVs is unreliable in planning
      their management. Clinicians can neither predict those who will require duplex
      scanning nor correctly identify DVR. Even experienced surgeons often "get it
      wrong" when assessing primary uncomplicated veins despite being certain about the
      diagnosis. Therefore, an "all-comers" duplex imaging policy should be implemented
      if optimal management is to be achieved.

PMID- 16798026
TI  - Misleading algorithms in the treatment of thoracic aortic injuries.

PMID- 16798027
TI  - Endovascular stent grafts as a safe secondary option for para-anastomotic
      abdominal aortic aneurysm.
AB  - OBJECTIVE: To describe our experience of endovascular repair of para-anastomotic
      aortic aneurysm. METHODS AND RESULTS: From March 2001 to December 2004 we
      identified 6 patients with a para-anastomotic aortic aneurysms following previous
      open repair of abdominal aortic aneurysm. All patients were treated with
      endovascular surgery under epidural anaesthesia. There were no major
      complications, surgical conversions or deaths. Four patients received a
      bifurcated aortic stent-graft, and two an aorto-uniliac stent-graft followed by a
      femoro-femoral bypass. At follow-up (mean 26.1+/-10.2 months) there were no
      deaths, endoleaks or graft migrations observed. CONCLUSION: Endovascular surgery,
      avoiding general anesthesia and re-laparotomy, is the ideal technique for
      treatment of this complication resulting from failed primary conventional AAA
      repair.

PMID- 16798028
TI  - Dynamic cine-CT angiography for the evaluation of the thoracic aorta; insight in
      dynamic changes with implications for thoracic endograft treatment.
AB  - OBJECTIVE: Thoracic aneurysm preoperative imaging is performed using static
      techniques without consideration of normal aortic dynamics. Improved
      understanding of the native aortic environment into which thoracic endografts are
      placed may aid in device selection. It is unclear what comprises normal thoracic
      aortic pulsatility. We studied these phenomena dynamically using ECG-gated 64
      slice CTA. METHODS: Maximum diameter and area change per cardiac cycle was
      measured at surgically relevant anatomic thoracic landmarks in ten patients; 1.0
      cm proximal and distal to the subclavian artery, 3.0 cm distal to the subclavian
      artery, and 3.0 cm proximal to the celiac trunk. Data was acquired using a novel
      ECG-gated dynamic 64-slice CT scanner during a single breath hold with a standard
      radiation dose and contrast load. Eight gated data sets, covering the cardiac
      cycle were reconstructed, perpendicular to the central lumen. RESULTS: There is
      impressive change in both maximum diameter and area in the thoracic aorta during
      the cardiac cycle. Mean maximum diameter changes of greater than 10% are observed
      in the typical sealing zones of commercially available endografts corresponding
      to diameter increases of up to 5mm. Aortic area increases by over 5% per cardiac
      cycle. CONCLUSIONS: ECG-gated dynamic CTA with standard radiation dose is
      feasible on a 64-slice scanner and provides insight into (patho) physiology of
      thoracic aortic conformational changes. Clinicians typically oversize thoracic
      endografts by 10%. With aortic pulsatility resulting in diameter changes of up to
      17.8%, the potential exists for endograft undersizing, graft migration,
      intermittent type I endoleak, and poor patient outcome. Furthermore, aortic
      pulsatility is not evenly distributed, and non-circular stentgraft designs should
      be considered in the future since aortic distension in the aneurysm neck is not
      evenly distributed.

PMID- 16798029
TI  - Endovascular treatment of acute haemoptysis secondary to aortobronchial fistula.
AB  - INTRODUCTION: Aortobronchial fistula is a rare but potentially fatal condition.
      We report our experience in the endovascular treatment of acute haemoptysis in
      high risk patients with aortobronchial fistula. REPORT: Between May 2002 and
      December 2004 five patients presenting with acute haemoptysys due to
      aortobronchial fistula were treated by endovascular stent grafting of the
      descending thoracic aorta. We did not observe intraoperative or perioperative
      mortality, stent-graft infection or paraplegia. In one case endoleak occurred.
      CONCLUSION: Endovascular stent-grafting represents an effective therapeutic
      option for the management of aortobronchial fistula. Careful follow up of the
      patients is mandatory.

PMID- 16798030
TI  - A phosphoglucose isomerase mutant in Aspergillus nidulans is defective in hyphal
      polarity and conidiation.
AB  - Upon germination Aspergillus nidulans swoM1 exhibits abnormal development by
      extending a primary germ tube that quickly reverts to isotropic growth and
      results in an enlarged, swollen apex with pronounced wall thickenings. Apical
      lysis occurs in 38% of the germlings. A point mutation in the AN6037.3 gene
      encoding the only phosphoglucose isomerase in A. nidulans is responsible for the
      defect. Loss of polarity is bypassed when glucose is replaced with alternate
      carbon sources but in all cases the mutant is unable to conidiate due to a block
      in conidiophore development at vesicle formation. In conidiophores SwoM::GFP
      localizes to multiple punctate, foci within each actively growing cell type, and
      to multiple foci in mature dormant conidia. In hyphae SwoM::GFP localized to two
      rings spanning the center of mature septa. In hyphae localization is concentrated
      at actively growing hyphal tips.

PMID- 16798031
TI  - Elevated circulating levels of markers of oxidative-nitrative stress and
      inflammation in a genetic rat model of metabolic syndrome.
AB  - Metabolic syndrome is a cluster of metabolic diseases that in essence greatly
      promotes progression of atherosclerosis. We used a genetic model of the metabolic
      syndrome, the SHR/NDmcr-cp (SHR/cp) rat, from 6 to 40 weeks of age to investigate
      whether systemic oxidative stress, a major cause of atherosclerosis, increases in
      this syndrome. Nine-week-old male rats already showed manifestations of metabolic
      syndrome, including heavier body weight, higher blood pressure and higher levels
      of serum glucose, insulin and various lipids compared to the age-matched Wistar
      Kyoto (WKY) rats used as a genetic control. These metabolic parameters gradually
      progressed with age. Likewise, the serum levels of oxidative stress markers,
      including lipid peroxides, which oxidatively modify low-density lipoprotein (LDL)
      and 8-hydroxydeoxyguanosine (8-OHdG), gradually increased in SHR/cp rats. The
      serum levels of 3-nitrotyrosine and 3-chlorotyrosine also persistently increased,
      indicating the involvement of peroxynitrite or myeloperoxidase-catalyzed
      oxidation. In addition, high-sensitivity C-reactive protein (hsCRP), an early
      marker of inflammation, temporarily increased in SHR/cp rats compared to WKY
      rats. These findings suggest that oxidative stress, as well as nitrative stress
      and inflammation, increases in the metabolic syndrome, which may contribute to
      the development of atherosclerosis.

PMID- 16798032
TI  - Multi-dimensional 1H-13C HETCOR and FSLG-HETCOR NMR study of sphingomyelin
      bilayers containing cholesterol in the gel and liquid crystalline states.
AB  - (13)C cross polarization magic angle spinning (CP-MAS) and (1)H MAS NMR spectra
      were collected on egg sphingomyelin (SM) bilayers containing cholesterol above
      and below the liquid crystalline phase transition temperature (T(m)). Two
      dimensional (2D) dipolar heteronuclear correlation (HETCOR) spectra were obtained
      on SM bilayers in the liquid crystalline (L(alpha)) state for the first time and
      display improved resolution and chemical shift dispersion compared to the
      individual (1)H and (13)C spectra and significantly aid in spectral assignment.
      In the gel (L(beta)) state, the (1)H dimension suffers from line broadening due
      to the (1)H-(1)H homonuclear dipolar coupling that is not completely averaged by
      the combination of lipid mobility and MAS. This line broadening is significantly
      suppressed by implementing frequency switched Lee-Goldburg (FSLG) homonuclear
      (1)H decoupling during the evolution period. In the liquid crystalline (L(alpha))
      phase, no improvement in line width is observed when FSLG is employed. All of the
      observed resonances are assignable to cholesterol and SM environments. This study
      demonstrates the ability to obtain 2D heteronuclear correlation experiments in
      the gel state for biomembranes, expands on previous SM assignments, and presents
      a comprehensive (1)H/(13)C NMR assignment of SM bilayers containing cholesterol.
      Comparisons are made to a previous report on cholesterol chemical shifts in
      dimyristoylphosphatidylcholine (DMPC) bilayers. A number of similarities and some
      differences are observed and discussed.

PMID- 16798033
TI  - Real-time monitoring of drug-induced changes in the stomach acidity of living
      rats using improved pH-sensitive nitroxides and low-field EPR techniques.
AB  - New improved pH-sensitive nitroxides were applied for in vivo studies. An
      increased stability of the probes towards reduction was achieved by the
      introduction of the bulky ethyl groups in the vicinity of the paramagnetic NO
      fragment. In addition, the range of pH sensitivity of the approach was extended
      by the synthesis of probes with two ionizable groups, and, therefore, with two
      pKa values. Stability towards reduction and spectral characteristics of the three
      new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band
      electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and
      field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly
      synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl
      2,5-dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the
      application in the stomach due to both higher stability and convenient pH
      sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double
      resonance imaging (PEDRI) techniques were used to detect the nitroxide
      localization and acidity in the rat stomach. Improved probe characteristics
      allowed us to follow in vivo the drug-induced perturbation in the stomach acidity
      and its normalization afterwards during 1 h or longer period of time. The results
      show the applicability of the techniques for monitoring drug pharmacology and
      disease in the living animals.

PMID- 16798034
TI  - Chronic obstructive pulmonary disease: histopathology, inflammation and potential
      therapies.
AB  - Chronic obstructive pulmonary disease (COPD) is a major worldwide health burden
      with increasing morbidity, mortality and health care cost. It is a slowly
      progressive chronic inflammatory condition that affects the conducting airways
      (both large and small) and lung parenchyma. In COPD, inflammation is evident
      early on even in mild disease and increases with disease severity. Recent
      advances in our knowledge demonstrate, by comparison with asthma, the
      distinctive, "abnormal" or exaggerated inflammatory processes involved in the
      pathogenesis of COPD and thus identify novel therapeutic targets that could
      potentially impact on disease progression. The present review will focus on what
      is known of the abnormal inflammatory response of COPD in different regions of
      the conducting airways and lung. Novel, potentially promising approaches to
      therapy are presented.

PMID- 16798035
TI  - The role of the bronchial circulation in the acute lung injury resulting from
      burn and smoke inhalation.
AB  - Smoke inhalation in burn patients is a serious medical problem around the world.
      Inhalation injury increases mortality in addition to increasing infections,
      ventilator-days, and hospital stays. There are also large numbers of patients
      subjected to smoke inhalation without burns from cooking fires, burning crops and
      forest fires. The injury results in a fall in arterial oxygenation as a result of
      airway blockade, increased pulmonary transvascular fluid flux and loss of hypoxic
      pulmonary vasoconstriction. The changes in cardiopulmonary function are mediated
      at least in part by reactive oxygen and nitrogen species. Nitric oxide (NO) is
      generated by both inducible and constitutive isoforms of nitric oxide synthase
      (NOS). NO combines with superoxide to form reactive nitrogen species such as
      peroxynitrite. These reactive nitrogen species can be detected by measuring their
      reaction products such as 3-nitrotyrosine. The latter is elevated in the airway
      following smoke/burn injury. The control of NO formation involves poly (ADP
      ribose) polymerase (PARP) and its ability to up-regulate the activity of nuclear
      transcription factors through ribosylation. Present data also support a major
      role for the bronchial circulation in the injury since blockade of bronchial
      blood flow will also minimize the pulmonary injury. The data suggest that
      cytotoxins or activated cells are formed in the airway and carried to the
      parenchyma. These materials cause the formation of oedema and a reduction of
      PaO(2).

PMID- 16798036
TI  - Membrane-bound alkaline phosphatase from ectopic mineralization and rat bone
      marrow cell culture.
AB  - Cells from rat bone marrow exhibit the proliferation-differentiation sequence of
      osteoblasts, form mineralized extracellular matrix in vitro and release alkaline
      phosphatase into the medium. Membrane-bound alkaline phosphatase was obtained by
      method that is easy to reproduce, simpler and fast when compared with the method
      used to obtain the enzyme from rat osseous plate. The membrane-bound alkaline
      phosphatase from cultures of rat bone marrow cells has a MW(r) of about 120 kDa
      and specific PNPP activity of 1200 U/mg. The ecto-enzyme is anchored to the
      plasma membrane by the GPI anchor and can be released by PIPLC (selective
      treatment) or polidocanol (0.2 mg/mL protein and 1% (w/v) detergent). The
      apparent optimum pH for PNPP hydrolysis by the enzyme was pH 10. This fraction
      hydrolyzes ATP (240 U/mg), ADP (350 U/mg), glucose 1-phosphate (1100 U/mg),
      glucose 6-phosphate (340 U/mg), fructose 6-phosphate (460 U/mg), pyrophosphate
      (330 U/mg) and beta-glycerophosphate (600 U/mg). Cooperative effects were
      observed for the hydrolysis of PPi and beta-glycerophosphate. PNPPase activity
      was inhibited by 0.1 mM vanadate (46%), 0.1 mM ZnCl2 (68%), 1 mM levamisole
      (66%), 1 mM arsenate (44%), 10 mM phosphate (21%) and 1 mM theophylline (72%). We
      report the biochemical characterization of membrane-bound alkaline phosphatase
      obtained from rat bone marrow cells cultures, using a method that is simple,
      rapid and easy to reproduce. Its properties are compared with those of rat
      osseous plate enzyme and revealed that the alkaline phosphatase obtained has some
      kinetics and structural behaviors with higher levels of enzymatic activity,
      facilitating the comprehension of the mineralization process and its function.

PMID- 16798037
TI  - Relationship between glutathione S-transferase, catalase, oxygen consumption,
      lipid peroxidation and oxidative stress in eggs and larvae of Boophilus microplus
      (Acarina: Ixodidae).
AB  - Glutathione S-transferases (GSTs) are enzymes that act in excretion of
      physiologic and xenobiotic substances, protecting cells against chemical toxicity
      and stress. In this work, we characterized the enzymatic activity of GST in eggs
      and larvae of cattle tick Boophilus microplus, on different days after
      oviposition and eclosion. The results showed that the GST activity varied
      depending on the time elapsed after oviposition and eclosion. Molecules involved
      in mechanism of protection from oxidative stress are correlated with the increase
      in GST activity. The oxygen consumption kinetics showed a positive correlation
      with the increase in GST activity during embryogenesis. A high content of
      thiobarbituric acid reactive substances were observed in egg and larva extracts,
      indicating that ticks face high oxidative stress during embryogenesis and aging.
      In eggs and larvae, GST activity can be correlated to kinetic parameters of
      oxidative stress such as catalase and glutathione. In addition, GST activity
      showed strong positive correlation with lipid peroxidation, an indication that it
      plays a role in oxidant defences in eggs.

PMID- 16798039
TI  - Phenotypic variability of mitochondrial disease caused by a nuclear mutation in
      complex II.
AB  - We report a patient with relatively mild Leigh syndrome and mitochondrial
      respiratory chain complex II deficiency caused by a homozygous G555E mutation in
      the nuclear encoded flavoprotein subunit of succinate dehydrogenase. This
      mutation has previously been reported in a lethal-infantile presentation of
      complex II deficiency. Such marked phenotypic heterogeneity, although typical of
      heteroplasmic mutations in the mitochondrial genome, is unusual for nuclear
      mutations. Comparable activities and stability of mitochondrial respiratory chain
      enzymes were demonstrated in both patients, so other reasons for the phenotypic
      variability are considered.

PMID- 16798040
TI  - A basal promoter element recognized by free RNA polymerase sigma subunit
      determines promoter recognition by RNA polymerase holoenzyme.
AB  - During transcription initiation by bacterial RNA polymerase, the sigma subunit
      recognizes the -35 and -10 promoter elements; free sigma, however, does not bind
      DNA. We selected ssDNA aptamers that strongly and specifically bound free
      sigma(A) from Thermus aquaticus. A consensus sequence, GTA(C/T)AATGGGA, was
      required for aptamer binding to sigma(A), with the TA(C/T)AAT segment making
      interactions similar to those made by the -10 promoter element (consensus
      sequence TATAAT) in the context of RNA polymerase holoenzyme. When in dsDNA form,
      the aptamers function as strong promoters for the T. aquaticus RNA polymerase
      sigma(A) holoenzyme. Recognition of the aptamer-based promoters depends on the
      downstream GGGA motif from the aptamers' common sequence, which is contacted by
      sigma(A) region 1.2 and directs transcription initiation even in the absence of
      the -35 promoter element. Thus, recognition of bacterial promoters is controlled
      by independent interactions of sigma with multiple basal promoter elements.

PMID- 16798038
TI  - Specific protein kinase C isoforms as transducers and modulators of insulin
      signaling.
AB  - Recent studies implicate specific PKC isoforms in the insulin-signaling cascade.
      Insulin activates PKCs alpha, betaII, delta and zeta in several cell types. In
      addition, as will be documented in this review, certain members of the PKC family
      may also be activated and act upstream of PI3 and MAP kinases. Each of these
      isoforms has been shown one way or another either to mimic or to modify insulin
      stimulated effects in one or all of the insulin-responsive tissues. Moreover,
      each of the isoforms has been shown to be activated by insulin stimulation or
      conditions important for effective insulin stimulation. Studies attempting to
      demonstrate a definitive role for any of the isoforms have been performed on
      different cells, ranging from appropriate model systems for skeletal muscle,
      liver and fat, such as primary cultures, and cell lines and even in vivo studies,
      including transgenic mice with selective deletion of specific PKC isoforms. In
      addition, studies have been done on certain expression systems such as CHO or
      HEK293 cells, which are far removed from the tissues themselves and serve mainly
      as vessels for potential protein-protein interactions. Thus, a clear picture for
      many of the isoforms remains elusive in spite of over two decades of intensive
      research. The recent intrusion of transgenic and precise molecular biology
      technologies into the research armamentarium has opened a wide range of
      additional possibilities for direct involvement of individual isoforms in the
      insulin signaling cascade. As we hope to discuss within the context of this
      review, whereas many of the long sought-after answers to specific questions are
      not yet clear, major advances have been made in our understanding of precise
      roles for individual PKC isoforms in mediation of insulin effects. In this
      review, in which we shall focus our attention on isoforms in the conventional and
      novel categories, a clear case will be made to show that these isoforms are not
      only expressed but are importantly involved in regulation of insulin metabolic
      effects.

PMID- 16798041
TI  - Field performance and new uses of rapid influenza testing in Thailand.
AB  - OBJECTIVES: Rapid influenza tests are increasingly used in surveillance systems
      and for clinical care in Southeast Asia. However, the performance and utility of
      rapid influenza tests under field conditions in rural Southeast Asia has not been
      evaluated. METHODS: In the context of a larger study on the causes of respiratory
      illness in rural Thailand, we used a rapid test to collect data on influenza
      burden, seasonality, and cost of illness. We compared the performance of the
      QuickVue Influenza Test to tissue cell viral culture and reverse transcriptase
      polymerase chain reaction (RT-PCR) among 1092 Thai patients meeting the World
      Health Organization case definition for influenza-like illness over a 12-month
      period. RESULTS: The sensitivity and specificity of the QuickVue test compared to
      viral culture were 77% and 96%, respectively. Rapid influenza tests were useful
      to describe the seasonality of influenza, estimate the cost of illness, increase
      the sensitivity of surveillance, conduct outbreak responses, and guide evaluation
      of suspected avian influenza virus infections. CONCLUSIONS: Despite their high
      cost, rapid influenza diagnostic tests are useful tools for influenza research,
      surveillance, and outbreak investigations in Southeast Asia.

PMID- 16798042
TI  - Comparison between doxycycline-rifampin-amikacin and doxycycline-rifampin
      regimens in the treatment of brucellosis.
AB  - BACKGROUND: Combination drug therapy of brucellosis leads to recovery of
      symptoms, shortening of symptomatic interval, and decrease in morbidity rate, but
      single drug therapy is associated with more relapse episodes and a higher rate of
      drug resistance. Different drug combinations have been evaluated in the treatment
      of brucellosis. Considering the failure of treatment and relatively high rate of
      relapse of the disease with the World Health Organization's (WHO) recommended
      therapeutic regimen, we evaluated a new regimen that we assumed would increase
      the success of treatment and decrease the rate of relapse. In this study we
      compare the standard regimen of the WHO, doxycycline-rifampin (DR), to triple
      therapy with doxycycline-rifampin-amikacin (ADR). METHODS: Two hundred and twenty
      eight consecutive patients with brucellosis, who attended Hamedan Sina Hospital
      between 1999 and 2001, whether seen as outpatients or as inpatients, were
      enrolled in the study. The participants were randomly allocated to the DR group
      (receiving doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day
      every morning, both taken orally for eight weeks) or the ADR group (receiving
      doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day every
      morning, both taken orally for eight weeks, plus 7.5 mg/kg amikacin
      intramuscularly twice a day for seven days). The patients were checked for the
      relief of symptoms, drug side-effects, and relapse of disease during the
      treatment and follow-up. RESULTS: Of the 228 patients enrolled, eight were
      withdrawn - four patients from the DR group and four from the ADR group. Of the
      remaining 220 participants (110 in the ADR group and 110 in the DR group), 107
      were male (48.6%) and 113 were female (51.4%). Mean age was 35.7+/-17 years in
      the ADR group and 37+/-18.4 years in the DR group (p=0.5). In the DR group, 97
      (88.2%) and in the ADR group, 106 (96.4%) of the patients had relief of symptoms
      (a significant difference by Chi-square test (p=0.04)). After completion of
      treatment, and at the sixth month follow-up, nine (9.3%) patients in the DR group
      and six (5.7%) in the ADR group experienced a relapse of the disease, with no
      significant difference (p=0.4). Mild side-effects were found in only 10 patients,
      and none required discontinuation of the therapeutic regimen. Of these patients,
      four were from DR group and six from ADR group; no significant difference was
      observed (p=0.7). CONCLUSIONS: Given the fact that the ADR regimen had a higher
      efficacy and more rapid action in terms of relief of symptoms compared to the DR
      regimen, and that no significant difference in drug side-effects and disease
      relapse existed in the patients of either group, adding amikacin to the DR
      standard treatment regimen seems beneficial.

PMID- 16798043
TI  - Identification of a cross-reactive HLA-DRB1*0301-restricted CD4 T cell response
      directed against cholesterol-binding cytolysins from two different pathogens.
AB  - Cholesterol-binding cytolysins constitute an evolutionarily conserved family of
      pore-forming proteins expressed by different gram-positive pathogens.
      Listeriolysin O, one well-characterized member of the cytolysin family, is also
      known to induce specific CD4 and CD8 T cell responses upon infection of mice with
      Listeria monocytogenes. Here we describe an HLA-DRB1*0301-restricted
      listeriolysin O-derived T cell epitope that is conserved among several members of
      the cytolysin family. An HLA-DRB1*0301-restricted CD4+ T cell line, established
      from spleen lymphocytes of L. monocytogenes-infected HLA-DRB1*0301-transgenic
      mice, cross-reacted with a homologous peptide from perfringolysin O, a cytolysin
      expressed by Clostridium perfringens. Ex vivo analysis of infected mice revealed
      an even broader cross-reaction of T cells with homologous peptides derived from
      perfringolysin O, streptolysin O, and cereolysin O. Interestingly, a cross
      reactive memory CD4+ T cell response against the homologous peptides derived from
      listeriolysin O and perfringolysin O could also be detected in the blood from
      healthy HLA-DRB1*0301+ human donors. Remarkably, this response was even present
      in donors who did not exhibit a memory T cell reactivity against a second, non
      conserved HLA-DRB1*0301-restricted LLO-derived CD4 T cell epitope, suggesting
      that cytolysin-producing bacteria other than L. monocytogenes can stimulate a
      cross-reactive cytolysin-specific immunity.

PMID- 16798044
TI  - PE_PGRS proteins are differentially expressed by Mycobacterium tuberculosis in
      host tissues.
AB  - Characterization of PE_PGRS gene expression will help define the role of this
      protein family in the biology of Mycobacterium tuberculosis. In this report,
      quantitative real-time RT-PCR (QRT-PCR) was implemented to assess expression of
      three PE_PGRS genes (rv0746, rv1651c and rv1818c) under different experimental
      conditions. The three PE_PGRS genes showed a similar expression profile in axenic
      cultures, with a significant up-regulation occurring at late log and early
      stationary phases. rv1651c gene expression increased following intracellular
      growth in bone marrow-derived macrophages but not in type-II human pneumocytes,
      while rv0746 was induced in both in vitro systems. Following the infection of
      mice with M. tuberculosis, expression levels of rv1651c and rv0746 normalized to
      ftsZ and 16S rRNA were highest in the spleen tissue during the chronic stages of
      murine tuberculosis, with a >20- and >30-fold up-regulation, respectively. Levels
      of expression remained lower in the lung over the same time period. Expression of
      the rv1818c gene did not change significantly under different experimental
      conditions tested. The results of this study indicate that M. tuberculosis can
      differentially regulate expression of PE_PGRS genes and that genes such as rv0746
      and rv1651c are significantly induced while M. tuberculosis persists in host
      cells and tissues.

PMID- 16798045
TI  - Hereditary hypophosphatemic rickets with hypercalciuria.

PMID- 16798046
TI  - Recommendations of the French Society for Rheumatology. TNFalpha antagonist
      therapy in rheumatoid arthritis.
AB  - OBJECTIVES: To develop recommendations for TNFalpha-antagonist therapy in
      patients with rheumatoid arthritis (RA) seen in everyday practice, under the
      aegis of the French Society for Rheumatology. METHOD: We used the methods
      recommended by the French Agency for Healthcare Accreditation and Evaluation, the
      AGREE collaboration, and the European League against Rheumatism (EULAR). The
      recommendations focus on patient selection, monitoring, and treatment
      adjustments. RESULTS: Criteria for selecting patients eligible for TNFalpha
      antagonist treatment of RA include: 1) a definitive diagnosis of RA; 2) disease
      activity for longer than 1 month, including presence of objective signs of
      inflammation; or radiographic progression; 3) previous failure of methotrexate in
      the highest tolerated dosage or of another disease-modifying antirheumatic drug
      in patients with contraindications to methotrexate; 4) absence of
      contraindications to TNFalpha-antagonist therapy. When starting TNFalpha
      antagonist therapy 1) a thorough baseline evaluation should be conducted; 2) any
      of the three available agents can be used, as no differences in efficacy have
      been identified in patient populations; 3) concomitant methotrexate therapy is
      recommended regardless of the TNFalpha antagonist used; and 4) patients should
      receive standardized follow-up at regular intervals. Treatment adjustments should
      be based on the following: 1) the treatment objective is achievement of a EULAR
      response; 2) when such a response is not achieved, the dosage or dosing interval
      can be changed, or the patient can be switched to another TNFalpha antagonist; 3)
      in patients who experience intolerance to a TNFalpha antagonist, another TNFalpha
      antagonist may be tried, depending on the nature of the adverse event; 4)
      occurrence of a remission should lead to a reduction in symptomatic medications,
      most notably glucocorticoids where used; in the event of a prolonged remission,
      either the TNFalpha antagonist or the concomitant disease-modifying antirheumatic
      drug may be reduced. CONCLUSION: These recommendations are intended to help
      physicians use TNFalpha antagonists in their everyday practice with RA patients.
      They do not constitute regulations.

PMID- 16798047
TI  - From "periarthritis" to hip "rotator cuff" tears. Trochanteric tendinobursitis.

PMID- 16798048
TI  - Prognostic markers for systemic sclerosis.
AB  - The prognosis of systemic sclerosis depends chiefly on the extent of the skin
      lesions, which correlates with the severity of the cardiovascular, pulmonary, and
      renal manifestations. An erythrocyte sedimentation rate greater than 15-25 mm/h
      or a hemoglobin level lower than 12.5-11 g/dl is associated with a 2.5- to 3-fold
      increase in mortality. Anticentromere antibodies are associated with delayed
      pulmonary hypertension, anti-topoisomerase I antibodies (Scl 70) with
      interstitial lung disease, and anti-RNA polymerase III antibodies with
      renovascular hypertension. The risk of death is directly related to the
      autoantibody pattern. For instance, in a study of 1432 cases from the Pittsburgh
      Scleroderma Databank, 10-year survival among patients with limited cutaneous
      disease was 88% in the group with anti-U1-RNP, 75% in the group with
      anticentromere antibodies, 72% in the group with anti-PmScl, and 65% in the group
      with anti-Th/To. Ten-year survival in patients with diffuse cutaneous disease was
      64% with anti-topoisomerase antibodies, 61% with anti-U3-RNP, and 75% with anti
      RNA polymerase III. Several prognostic markers are also available for predicting
      the risk of organ involvement. For instance, serum levels of KL-6, surfactant
      proteins SP-A and SP-D, the collagen peptide PIIINP, and homocysteine are
      associated with the risk of fibrosing alveolitis. Serum levels of CD40L and NP
      ProBNP, circulating endothelial cells, and serum anticardiolipin titers correlate
      with the risk of arterial hypertension. Serum VCAM1 and markers for oxidative
      stress such as carboxyl terminus residues predict the risk of vascular disease.
      Other serum markers for organ involvement are under study, although their
      predictive performance remains to be evaluated.

PMID- 16798050
TI  - Automatic continuous monitoring of rectal temperature using a button-type thermo
      data logger.
AB  - We performed automatic continuous monitoring of rectal and ambient temperatures
      using button-type thermo data loggers in autopsy cases. The button-type data
      loggers have a battery-powered memory that can record 2048 temperature readings.
      The measurement intervals and other initial settings are determined by computer
      software, and the measurements were taken at 5-min intervals for this study. At
      autopsy, the data loggers were retrieved and recorded temperature graphs were
      produced. This study obtained three representative cases. In one case, the button
      type data logger was not discharged regardless of how the body was moved after
      the device was inserted into the rectum. In two other cases, the cooling curves
      of the rectal temperature readings clearly followed changes in ambient cooling
      conditions. The advantages of the tested devices are their small size (diameter,
      17.4 mm; thickness, 5.9 mm) and ease of insertion into the rectum, requiring no
      special skills. Many temperature-based algorithms to determine time of death have
      been developed, and as a matter of course, the temperature values must be
      accurate and reliable. Ensuring the validity of each temperature reading requires
      continuous data from an internal data logger. A button-type data logger is ideal
      for this purpose.

PMID- 16798049
TI  - [Ovarian cryopreservation: clinical and ethical problems arisen further to study
      on cases of ovarian cryopreservation].
AB  - OBJECTIVE: An early ovarian failure and sterility, on patients often still young,
      may result from some of the anticancerous treatments. Ovarian cryopreservation is
      a research way for fertility restoration on patients who will have gonadotoxic
      treatment. The aim of our work was to study the cases of ovarian tissue preserved
      in our Department, enabling us to assess the clinical and ethical problems of
      this technique. PATIENTS AND METHODS: A retrospective study was conducted from
      January 2001 onwards up to October 2005, on 14 patients, whose ovarian cortex was
      frozen our the University Fertility Center (Hopital de la Conception, Marseille,
      France). RESULTS: In our study, the patients' average age was 17+/-5.5 and the
      median was 14 years [13-24]. Eight patients were under 18 (11+/-3-years-old). The
      cryopreservation indications were especially haematological (N = 9). More than
      half of the patients (N = 8) had undergone a gonadotoxic treatment before ovarian
      cryopreservation. DISCUSSION AND CONCLUSION: Ovarian cryopreservation is still a
      recent technology in reproductive medicine. The future of ovarian tissue after
      thawing, with its different techniques of autograft, is still not consensual.
      Experimental research remains essential to improve the freezing protocols and
      ovarian transplant in human medicine.

PMID- 16798051
TI  - Fungi can be a useful forensic tool.
AB  - We present a practical case in which the fungi have contributed to the estimation
      of postmortem interval of the cadaver. A 71-year-old man wearing a shirt and
      pants was found dead at the bottom of an open well about 6m below the ground in
      his garden. Externally the face was dotted with colonies of white fungi, which
      was devoid of dipteran larvae and other insects. The fungi were identified as
      Penicillium sp. and Aspergillus terrous. These fungi, widely inhabit in the life
      circumstances, can generally colonize 3-7 days after attaching on the subjects.
      The appearance of the body surface, the state of decomposition of various organs,
      police information describing that the man had last been seen 12 days before
      discovery and the fungal evidence indicated that the man had been dead for about
      10 days. We suggest that fungi can provide an useful means of estimating the
      minimum interval since death when forensic entomology is not applicable.
      Although, no data about growth rates of the fungi on human cadavers have been
      available, further researches should be needed to clarify the successive
      colonization of fungi on human cadavers.

PMID- 16798052
TI  - Allele frequency distribution and haplotype of eleven hemizygous short tandem
      repeats in Jordanians.
AB  - The haplotype and allele frequency distributions of the Y-chromosomal STR markers
      DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437,
      DYS438, and DYS439 were determined in a sample of 97 unrelated males from Jordan.

PMID- 16798053
TI  - The efficacy of quantitative gait analysis by the GAITRite system in evaluation
      of parkinsonian bradykinesia.
AB  - The aim of this study was to assess whether the GAITRite gait analysis system an
      effective tool in evaluating parkinsonian bradykinesia. In their best ON and
      worst OFF states, 13 parkinsonian patients were asked to perform walking trail at
      their fastest velocity, and to submit to traditional timed tests. Significant
      correlations existed between OFF-ON improvement in gait parameters and in UPDRS
      III score (r(2)=0.59-0.78) except cadence. Among the gait parameters, stride
      length is the most effective indicator of timed test and UPDRS III score
      improvements. The GAITRite system is an efficient, yet effective device in
      evaluating parkinsonian bradykinesia and can be used as a substitute for the
      traditional timed test.

PMID- 16798055
TI  - Neighborhood and HIV infection among IDU: place of residence independently
      predicts HIV infection among a cohort of injection drug users.
AB  - This study was undertaken to investigate geographic residence in Vancouver's
      Downtown Eastside (DTES), Canada's poorest urban neighborhood, as an
      environmental risk factor for HIV infection among a cohort of injection drug
      users. HIV incidence rates were examined using Kaplan-Meier methods, and Cox
      proportional hazards regression was used to determine independent risk factors
      for HIV seroconversion. After intensive multivariate adjustment, DTES residence
      remained an independent predictor of HIV seroconversion (relative hazard=2.0, 95%
      CI: 1.4-3.0, p<0.001). These findings indicate the need for a greater recognition
      among policy-makers of geographic location as a risk factor for HIV incidence in
      urban settings and the need for further research to determine why place
      contributes so greatly to HIV risk. The findings also mark a need for prevention
      interventions to be appropriately targeted towards high-risk neighborhoods.

PMID- 16798054
TI  - Estimating the value of novel interventions for Parkinson's disease: an early
      decision-making model with application to dopamine cell replacement.
AB  - A long-term cost-effectiveness model for early decision-making and estimation of
      outcomes of novel therapeutic procedures for Parkinson's disease (PD) was
      developed based on the Hoehn and Yahr (HY) stages of PD. Results provided support
      for model validity. Model application to a future dopamine cell replacement
      therapy indicated long-term cost offsets and gains in quality-adjusted life years
      (QALYs) in early onset PD (HY III-IV), as compared to standard drug therapy. The
      maximum price premium (i.e., profit or compensation for developmental costs) for
      the intervention to remain cost-effective was estimated to euro12000-64000
      according to cost-per-QALY thresholds of euro38000-70000 and depending on whether
      all or only medical direct costs are considered. The study illustrates the value
      of early health economic modeling and the described model shows promise as a
      means to estimate outcomes and aid decision-making regarding novel interventions
      for PD.

PMID- 16798056
TI  - Citrate enhances in vitro metastatic behaviours of PC-3M human prostate cancer
      cells: status of endogenous citrate and dependence on aconitase and fatty acid
      synthase.
AB  - Prostate is a unique organ that produces and releases large amounts of citrate.
      This is reduced significantly in cancer and it is possible that citrate is
      (re)taken up and used as a metabolite to enhance cellular activity. The main
      purpose of this study was to determine how cytosolic citrate might affect in
      vitro metastatic cell behaviours (lateral motility, endocytosis and adhesion).
      Normal (PNT2-C2) and metastatic (PC-3M) human prostate cancer cells were used in
      a comparative approach. As regards intermediary metabolic enzymes, aconitase and
      fatty acid synthase, already implicated in prostate cancer, were evaluated. The
      level of intracellular citrate was significantly higher in PNT2-C2 cells under
      both control conditions and following preincubation in extracellular citrate.
      Supply of exogenous citrate enhanced endocytosis, lateral motility, decreased
      cell adhesion of PC-3M cells but failed to produce any effect on normal cells.
      Real-time PCR measurements showed that the mRNA levels of mitochondrial and
      cytosolic aconitases and fatty acid synthase were significantly higher in PC-3M
      cells. Correspondingly, aconitase activity was also higher in PC-3M cells. Using
      cerulenin (an inhibitor of fatty acid synthase), oxalomalate and fluorocitrate
      (inhibiting aconitases), we investigated the dependence of citrate-induced down
      regulation of cellular adhesion on aconitase and fatty acid synthase activities.
      It was concluded: (1) that strongly metastatic PC-3M cells stored less/utilised
      more cytosolic citrate than the normal PNT2-C2 cells and (2) that cancer cells
      could metabolise cytoplasmic citrate via aconitase and fatty acid synthase to
      enhance their metastatic behaviour.

PMID- 16798057
TI  - The role of thymidine phosphorylase and uridine phosphorylase in
      (fluoro)pyrimidine metabolism in peripheral blood mononuclear cells.
AB  - Thymidine phosphorylase (TP) and uridine phosphorylase (UP) catalyze the
      (in)activation of several fluoropyrimidines, depending on their catalytic
      activity and substrate specificity. Blood cells are the first compartment exposed
      to most anticancer agents. The role of white blood cells in causing toxic side
      effects and catalyzing drug metabolism is generally underestimated. Therefore we
      determined the contribution of the white blood cell compartment to drug
      metabolism, and we investigated the activity and substrate specificity of TP and
      UP for the (fluoro)pyrimidines thymidine (dThd), uridine (Urd), 5'-deoxy-5
      fluorouridine (5' dFUrd) and 5-fluorouracil (5FU) in peripheral blood mononuclear
      cells (PBMC) and undifferentiated monocytes and differentiated monocytes:
      macrophages and dendritic cells. PBMC had an IC50 of 742 microM exposed to
      5'dFUrd, increasing to > 2000 microM when both TP and UP activities were
      inhibited. Total phosphorolytic activity was higher with dThd than with Urd,
      5'dFUrd or 5FU. Using a specific TP inhibitor (TPI) and UP inhibitor (BAU) we
      concluded that dThd and Urd were preferentially converted by TP and UP,
      respectively, while 5'dFUrd and 5FU were mainly converted by TP (about 80%) into
      5FU and FUrd, respectively. 5FU was effectively incorporated into RNA. dThd
      conversion into thymine was highest in dendritic cells (52.6 nmol thymine/h/10(6)
      cells), followed by macrophages (two-fold) and undifferentiated monocytes (eight
      fold). TPI prevented dThd conversion almost completely. In conclusion, PBMC were
      relatively insensitive to 5'dFUrd, and the natural substrates dThd and Urd were
      preferentially converted by TP and UP, respectively. TP and UP were both
      responsible for converting 5'dFUrd/5FU into 5FU/FUrd, respectively.

PMID- 16798059
TI  - Expression of human telomerase reverse transcriptase (hTERT) protein is
      significantly associated with the progression, recurrence and prognosis of oral
      squamous cell carcinoma in Taiwan.
AB  - This study used an immunohistochemical technique to examine the expression of
      human telomerase reverse transcriptase (hTERT) protein in 82 specimens of OSCC,
      116 specimens of oral epithelial dysplasia (OED), and 21 specimens of normal oral
      mucosa (NOM). The cytoplasmic and nuclear hTERT staining intensity (SI; 0, no
      staining; 1, weak; 2, moderate; 3, strong), labeling indices (LIs, defined as the
      percentage of positive cells in total cells), and labeling scores (LSs, defined
      as LI x SI) in OSCC, OED, and NOM samples were calculated and compared among
      groups. The correlation between the cytoplasmic or nuclear hTERT LS in OSCCs and
      clinicopathological parameters or survival of OSCC patients was analyzed
      statistically. The mean cytoplasmic hTERT LSs increased significantly from NOM
      (87+/-17%) through OED (95+/-18%) to OSCC samples (114+/-33%, p=0.000). The mean
      nuclear hTERT LSs also increased from NOM (80+/-14%) to OED (91+/-20%) and then
      decreased to OSCC samples (86+/-35%) with no statistically significant difference
      among the 3 groups. A significant correlation was found between the higher mean
      cytoplasmic hTERT LSs and OSCCs occurring in male patients (p=0.023), with larger
      tumor sizes (T3 and T4, p=0.048), with more advanced clinical stages (stages 3
      and 4, p=0.033), or from patients with areca quid chewing (p= 0.029), cigarette
      smoking (p=0.027), or alcohol drinking habit (p=0.025). In addition, OSCC
      patients with nuclear hTERT LSs greater than 100% were prone to have a higher
      recurrence rate (p=0.044) and a lower 5-year survival rate (p=0.011). Our results
      indicate that the increased expression of hTERT protein is an early event in oral
      carcinogenesis and hTERT may be a biomarker for OSCCs. Measuring the amount of
      cytoplasmic or nuclear expression of hTERT in OSCC samples may predict the oral
      cancer progression, recurrence, and prognosis in Taiwan.

PMID- 16798058
TI  - Coronary vessel trees from 3D imagery: a topological approach.
AB  - We propose a simple method for reconstructing vascular trees from 3D images. Our
      algorithm extracts persistent maxima of the intensity on all axis-aligned 2D
      slices of the input image. The maxima concentrate along 1D intensity ridges, in
      particular along blood vessels. We build a forest connecting the persistent
      maxima with short edges. The forest tends to approximate the blood vessels
      present in the image, but also contains numerous spurious features and often
      fails to connect segments belonging to one vessel in low contrast areas. We
      improve the forest by applying simple geometric filters that trim short branches,
      fill gaps in blood vessels and remove spurious branches from the vascular tree to
      be extracted. Experiments show that our technique can be applied to extract
      coronary trees from heart CT scans.

PMID- 16798060
TI  - Imaging of oral cavity cancer.
AB  - Despite many advances in surgical techniques, technology, radiation therapy, and
      chemotherapy, survival rates for head and neck cancer (HNCa) have not improved
      significantly in decades, with many patients being diagnosed at advanced disease
      stages. Adequate assessment of oral cavity malignancies is critical for
      appropriate planning of surgical, radiation, and chemotherapy treatment. Imaging
      modalities used to evaluate the oral cavity include plain radiography (panoramic
      radiography and intraoral radiography), nuclear medicine scintigraphy, ultrasound
      (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron
      emission tomography (PET). This review describes these imaging techniques and
      their utility, primarily CT and MRI.

PMID- 16798061
TI  - A randomized phase III prospective trial of bethanechol to prevent radiotherapy
      induced salivary gland damage in patients with head and neck cancer.
AB  - The aim of this study was to verify whether the use of bethanechol during
      radiotherapy (RT) for head and neck cancer (HNC) prevents radiation-induced
      xerostomia and salivary flow reduction. Patients that would begin RT were
      randomly allocated into bethanechol (group 1) or artificial saliva (group 2).
      Whole resting saliva (WRS) and whole stimulated saliva (WSS) were collected from
      all the patients at the following four stages: baseline, during, immediately
      after, and at least two months after the end of RT. Xerostomia was assessed by a
      subjective visual analogue scale (VAS), and by asking patients whether they felt
      dry mouth. Forty-three patients were randomized into this trial. The use of
      bethanechol during RT for HNC cancer was associated with significantly higher WRS
      immediately after RT (p=0.03) in comparison to a similar cohort of patients who
      had not received bethanechol.

PMID- 16798062
TI  - CD44 expression and its relationship with MMP-9, clinicopathological factors and
      survival in oral squamous cell carcinoma.
AB  - We investigated the expression of CD44 and MMP-9 in primary oral squamous cell
      carcinoma (OSCC) and evaluated their association with each other and
      clinicopathological factors as well as their prognostic value during long term
      follow up. Histological samples from 138 OSCC patients were immunohistochemically
      stained for the expression of CD44 and MMP-9. The staining results were compared
      with conventional prognostic factors and their impacts to patients' prognosis
      were also studied with survival analyses. Irregular staining of CD44 in tumour
      cells was associated with poor tumour differentiation (p=0.003), higher clinical
      stage (III-IV) (p=0.049), and the presence of T3-4 tumour stage (p=0.03). Strong
      stromal MMP-9 staining intensity was correlated with poor tumour differentiation
      (p=0.03). In univariate survival analysis irregular staining of CD44 in tumour
      cells was related to poor disease free and overall survival (p=0.001 and p<0.001,
      respectively). In multivariate analysis CD44 staining was a significant
      independent predictor for overall (p=0.03) and disease free survival (p=0.003).
      MMP-9 expression showed no statistical significance in survival analyses. Strong
      stromal staining intensity of MMP-9 correlated with irregular staining of CD44 in
      tumour cells, but had no prognostic significance in the present cohort. However,
      irregular staining of CD44 predicted more advanced disease and shortened survival
      of the patients.

PMID- 16798063
TI  - Antiseptic effect of a novel alcohol-free mouthwash: a convenient prophylactic
      alternative for high-risk patients.
AB  - We developed an efficacious and non-irritant mouthwash that is alcohol-free and
      that has a low concentration of chlorhexidine, in order to be used for preventing
      oral cavity infections in immunocompromised and cancer patients. The novel
      mouthwash solution was tested for its antimicrobial efficacy against both free
      floating (planktonic) and the biofilm forms of Candida albicans. The solution was
      also tested against Klebsiella pneumoniae, Pseudomonas aeruginosa, and
      methicillin-resistant Staphylococcus aureus (MRSA), using a modification of a
      previously published method. The activity of the novel mouthwash was also
      compared with that of three commercially available mouthwashes. The experimental
      mouthwash showed efficacy against C. albicans, both in free-floating form and in
      biofilm. With higher concentration of chlorhexidine, the solution was also
      efficacious in inhibiting the growth of K. pneumoniae, P. aeruginosa, and MRSA.
      The antiseptic activity of the alcohol-free mouthwash against other bacterial
      organisms and C. albicans was comparable to other commercially available alcohol
      based mouthwash solutions. A novel alcohol-free mouthwash solution, that has low
      concentration of chlorhexidine, showed antiseptic effect against planktonic and
      biofilm forms of C. albicans and against K. pneumoniae, P. aeruginosa, and MRSA.

PMID- 16798064
TI  - Runt-related transcription factor 3 expression in human oral squamous cell
      carcinomas; implication for tumor progression and prognosis.
AB  - Runt-related transcription factor 3 (RUNX3) is a tumor suppressor factor of
      gastric cancer and appears to be an important component of the transforming
      growth factor-beta (TGF-beta)-induced tumor suppression pathway. This study aimed
      to analyze the expression of the RUNX3 protein in human oral normal epithelia,
      dysplasia and squamous cell carcinomas (SCCs), comparing it with
      clinicopathological profiles. Western blot analysis revealed the RUNX3 protein as
      a single band at 44kDa in oral non-neoplastic mucosa and SCC. The expression of
      RUNX3 protein was also examined in 10 normal epithelia, 51 dysplasias and 108
      oral SCCs. The labeling indices (LIs) of RUNX3, Ki-67, P21, P27 and the apoptotic
      index (AI) were evaluated using immunohistochemistry and the TUNEL method. The LI
      of RUNX3 was 7.7+/-1.6 in the normal epithelia, 20.8+/-2.7 in the dysplasias and
      9.0+/-1.3 in the SCCs. The LI of RUNX3 was significantly highest in the
      dysplasias, followed by the SCCs (p<0.05) and normal epithelia (p<0.05). The
      RUNX3 LI correlated with the histological differentiation of SCCs, being the
      highest in the well differentiated SCCs (p<0.01). In addition, RUNX3 expression
      was significantly related to the lower Ki-67 LI, but not to LI of P21 and P27,
      and AI in the SCCs. The survival rate was significantly lower in the patients
      with lower RUNX3 expression (<5%) than in those with higher expression (5%)
      (p<0.05). These results indicate that the expression of RUNX3 is correlated with
      histological differentiation, and inversely with cellular proliferation of the
      oral SCCs, and might be a new prognostic marker in the patients with oral SCC.

PMID- 16798065
TI  - Lipid signaling in pathogenic fungi.
AB  - Recent studies have highlighted the importance of lipid signaling molecules in
      the development and pathogenicity of clinically important fungi. In Cryptococcus
      neoformans, sphingolipid-derived diacylglycerol has been shown to induce the
      transcription of the putative virulence factor App1, which inhibits the
      phagocytosis of fungal cells by alveolar macrophages, as well as to activate the
      protein kinase C Pkc1, which promotes cell-wall stability and increased melanin
      production. In Candida albicans, exposure to the oxylipin farnesol causes the
      regulation of specific genes involved in hyphal development, drug resistance and
      iron acquisition. Farnesol increases resistance to oxidative stress in C.
      albicans but, interestingly, induces apoptotic-like cell death in Aspergillus
      nidulans, suggesting that this molecule has multiple and opposing functions.
      Finally, fungal cells secrete eicosanoids, which are lipid molecules with
      putative signaling functions in fungi, and the recent characterization of the
      first fungal enzymes associated with the production of eicosanoids in A. nidulans
      and Aspergillus fumigatus provides new insights into the understanding of the
      role of eicosanoid production in the biology of fungal pathogenesis.

PMID- 16798066
TI  - Oxidative DNA damage induced by hair dye components ortho-phenylenediamines and
      the enhancement by superoxide dismutase.
AB  - There is an association between occupational exposure to hair dyes and incidence
      of cancers. Permanent oxidant hair dyes are consisted of many chemical components
      including ortho-phenylenediamines. To clarify the mechanism of carcinogenesis by
      hair dyes, we examined DNA damage induced by mutagenic ortho-phenylenediamine (o
      PD) and its derivatives, 4-chloro-ortho-phenylenediamine (Cl-PD) and 4-nitro
      ortho-phenylenediamine (NO(2)-PD), using (32)P-labeled DNA fragments obtained
      from the human p16 and the p53 tumor suppressor gene. We also measured the
      content of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative
      DNA damage, in calf thymus DNA with an electrochemical detector coupled to a high
      performance liquid chromatograph. Carcinogenic o-PD and Cl-PD caused Cu(II)
      mediated DNA damage, including 8-oxodG formation, and antioxidant enzyme
      superoxide dismutase (SOD) enhanced DNA damage. o-PD and Cl-PD caused piperidine
      labile and formamidopyrimidine-DNA glycosylase-sensitive lesions at cytosine and
      guanine residues respectively in the 5'-ACG-3' sequence, complementary to codon
      273, a well-known hotspot of the human p53 tumor suppressor gene. UV-vis
      spectroscopic studies showed that the spectral change of o-PD and Cl-PD required
      Cu(II), and addition of SOD enhanced it. This suggested that SOD enhanced the
      rate of Cu(II)-mediated autoxidation of o-PD and Cl-PD, leading to enhancement of
      DNA damage. On the other hand, mutagenic but non-carcinogenic NO(2)-PD induced no
      DNA damage. These results suggest that carcinogenicity of ortho-phenylenediamines
      is associated with ability to cause oxidative DNA damage rather than bacterial
      mutagenicity.

PMID- 16798067
TI  - User interpretations of future information system use: a snapshot with
      technological frames.
AB  - Integrated information systems for managing patient data transform the nature of
      hospital work to the extent that the work practices, the responsibilities, even
      the professional identities are likely to undergo major changes. Therefore,
      during the organizational implementation of the IS, attention should be paid to
      the future users and how they understand and see what is going on. Here the focus
      is on these interpretation processes, analyzed as technological frames. That is,
      people develop different assumptions, expectations and knowledge concerning new
      technology. During this sense-making process they build their idea of that
      technology, its technological frame. We analyzed the pre-implementation frames
      that could be discerned in 24 interviews of hospital personnel. Main influences
      on the frames in this case were the work role in the organization, knowledge
      about the new system, and attitudes toward the old systems. The social context
      appeared to have a significant influence in the users' interpretation processes
      and the frames seemed to be congruent within one group. So far, the incongruence
      between groups appeared to have caused no major problems for the implementation.

PMID- 16798068
TI  - Extending the understanding of computerized physician order entry: implications
      for professional collaboration, workflow and quality of care.
AB  - OBJECTIVE: To describe the perceived effect of computerized physician order entry
      (CPOE) on professional collaboration, workflow and quality of care. DESIGN: Semi
      structured interviews with experts involved in the design, implementation and
      evaluation of computerized physician order systems in the United States.
      MEASUREMENTS: The interview transcripts were analyzed using six key concepts that
      identify context, professional collaboration, workflow and quality of care.
      RESULTS: The interviews reveal the complexity of CPOE. Although providers enter
      the orders, others collaborate in the decision-making process. There is a
      profound impact on workflow beyond that of the provider. While quality of care is
      the main impetus for implementation, it remains terribly difficult to measure the
      impact on quality. CONCLUSIONS: A proper understanding of CPOE as a collaborative
      effort and the transformation of the health care activities into integrated care
      programs requires an understanding of how orders are created and processed, how
      CPOE as part of an integrated system can support the workflow, and how risks
      affecting patient care can be identified and reduced, especially during hand-offs
      in the workflow.

PMID- 16798070
TI  - Participatory design of a collaborative clinical trial protocol writing system.
AB  - OBJECTIVE: To explore concrete approaches to socio-technical design of
      collaborative healthcare information systems and to design a groupware technology
      for collaborative clinical trial protocol writing. METHOD: We conducted "quick
      and dirty ethnography" through semi-structured interviews, observational studies,
      and work artifacts analysis to understand the group work for protocol
      development. We used participatory design through evolutionary prototyping to
      explore the feature space of a collaborative writing system. Our design
      strategies include role-based user advocacy, formative evaluation, and change
      management. RESULTS: Quick and dirty ethnography helped us efficiently understand
      relevant work practice, and participatory design helped us engage users into
      design and bring out their tacit work knowledge. Our approach that intertwined
      both techniques helped achieve a "work-informed and user-oriented" design. This
      research leads to a collaborative writing system that supports in situ
      communication, group awareness, and effective work progress tracking. The
      usability evaluation results have been satisfactory. The system design is being
      transferred to an organizational tool for daily use.

PMID- 16798069
TI  - Implementing a new ADT based on the HL7 version 3 RIM.
AB  - The University Hospitals of Geneva (HUG) are the result of the merge of six
      hospitals into one single organization. While a true fusion of the management has
      been effectively done, it was not the case 5 years after for several databases,
      and in particular the ADT (admission, discharge, transfer). In order to truly
      realize the fusion, a new ADT service has been built using state of the art
      technology and standards in order to replace the existing seven services. This
      paper presents the results of the redesign and development of the new ADT
      service. The data model, based on HL7 RIM, is described and the technologies
      selected are presented. Finally, a status after 1 year of production is
      presented.

PMID- 16798071
TI  - Critical incidents and journey mapping as techniques to evaluate the impact of
      online evidence retrieval systems on health care delivery and patient outcomes.
AB  - BACKGROUND: Online evidence retrieval systems are a potential tool in supporting
      evidence-based practice. Effective and tested techniques for assessing the impact
      of these systems on care delivery and patient outcomes are limited. PURPOSE AND
      METHODS: In this study we applied the critical incident (CI) and journey mapping
      (JM) techniques to assess the integration of an online evidence system into
      everyday clinical practice and its impact on decision making and patient care. To
      elicit incidents semi-structured interviews were conducted with 29 clinicians (13
      hospital physician specialists, 16 clinical nurse consultants (CNCs)) who were
      experienced users of the online evidence system. Clinicians were also asked
      questions about how they had first used the system and how their use and
      experiences had changed over time. These narrative accounts were then mapped and
      scored using the journey mapping technique. RESULTS: Clinicians generated 85
      critical incidents. Three categories of impact were identified: impact on
      clinical practice, impact on individual clinicians and impact on colleagues
      through the dissemination of information gained from the online evidence system.
      One quarter of these included specific examples of system use leading to
      improvements in patient care. Clinicians obtained an average journey mapping
      score of 22 out of a possible score of 36, demonstrating a good level of system
      integration. Average scores of doctors and CNCs were similar. However individuals
      with the same scores often had very different journeys in system integration.
      CONCLUSIONS: The CI technique provided clear examples of the way in which system
      use had influenced practice and care delivery. The JM technique was found to be a
      useful method for providing a quantification of the different ways and extent to
      which, clinicians had integrated system use into practice, and insights into how
      system use can influence organisational culture. The development of the journey
      mapping stages provides a structure by which the program logic of a clinical
      information system and its desired outcomes can be made explicit and be based
      upon users' experiences in everyday practice. Further work is required using this
      technique to assess its value as an evaluation method.

PMID- 16798072
TI  - HCV infection and chronic arthritis: Does viral replication matter?
AB  - BACKGROUND: HCV infection beside chronic hepatitis can induce immunological
      disorders with different clinical expressions such as chronic arthritis. AIM: To
      study the prevalence of arthritis in HCV-Ab positive patients and verify possible
      correlation with viral replication, hepatic damage and autoimmunity imbalance.
      STUDY DESIGN: Three hundred and eighty patients (196 M and 184 F) affected by HCV
      infection were examined and 38 (10%) were selected according to the presence of
      arthritis. Eight of them were excluded because arthritis raised before HCV
      infection. Each patient, once undergone liver biopsy, was evaluated for: clinical
      examination (articular evolution), Rx examination, serum expression of hepatic
      damage (mainly ALT), viral replication, and involvement of autoimmunity (ANA, RF,
      crioglobulins, AKA, CCP). RESULTS: Data from patients [Lamprecht P, Gause A,
      Gross WL. Cryoglobulinemic vasculitis. Arthritis Rheum 1999; 42:2507-16.] with
      AKA and CCP positivity were not considered for statistical examination because
      the clear correlation between rheumatoid arthritis and these parameters. The
      remaining 20 patients showed hepatic damage 47%, viral replication in 74%, RF
      42%, ANA 16%, crioglobulins 42% (RF positive). No correlation was evident between
      ANA serum concentrations and viral replication; furthermore a significant
      negative correlation between RF positivity and viral replication only in a
      subgroup of patients with serologic expression of hepatic damage was found.
      CONCLUSIONS: These data support hypothesis that the onset of arthritis and
      presence of autoimmunity parameters ANA, RF are not related to the viral
      replication but others mechanism immunological induced by HCV might be
      considered.

PMID- 16798073
TI  - Lipid efflux by the ATP-binding cassette transporters ABCA1 and ABCG1.
AB  - Plasma levels of high-density lipoproteins (HDL) and apolipoprotein A-I (apoA-I)
      are inversely correlated with the risk of cardiovascular disease. One major
      atheroprotective mechanism of HDL and apoA-I is their role in reverse cholesterol
      transport, i.e., the transport of excess cholesterol from foam cells to the liver
      for secretion. The ATP-binding cassette transporters ABCA1 and ABCG1 play a
      pivotal role in this process by effluxing lipids from foam cells to apoA-I and
      HDL, respectively. In the liver, ABCA1 activity is one rate-limiting step in the
      formation of HDL. In macrophages, ABCA1 and ABCG1 prevent the excessive
      accumulation of lipids and thereby protect the arteries from developing
      atherosclerotic lesions. However, the mechanisms by which ABCA1 and ABCG1 mediate
      lipid removal are still unclear. Particularly, three questions remain
      controversial and are discussed in this review: (1) Do apoA-I and HDL directly
      interact with ABCA1 and ABCG1, respectively? (2) Does cholesterol efflux involve
      retroendocytosis of apoA-I or HDL? (3) Which lipids are directly transported by
      ABCA1 and ABCG1?

PMID- 16798074
TI  - Microsomal preparations from plant and yeast acylate free fatty acids without
      prior activation to acyl-thioesters.
AB  - Acylation of fatty acids to hydroxy groups in cells generally require activation
      to a thioester (ACP or CoA) or transacylation from another oxygen ester. We now
      show that microsomal membranes from Arabidopsis leaves efficiently acylate free
      fatty acids to long chain alcohols with no activation of the fatty acids to
      thioesters prior to acylation. Studies of the fatty alcohol and fatty acids
      specificities of the reaction in membranes from Arabidopsis leaves revealed that
      long chain (C18-C24) unsaturated fatty alcohols and C18-C22 unsaturated fatty
      acids were preferred. Microsomal preparations from Arabidopsis roots and leaves
      and from yeast efficiently synthesized ethyl esters from ethanol and free fatty
      acids. This reaction also occurred without prior activation of the fatty acid to
      a thioester. The results presented strongly suggest that wax ester and ethyl
      ester formation are carried out by separate enzymes. The physiological
      significance of the reactions in plants is discussed in connection to suberin and
      cutin synthesis. The results also have implication regarding the interpretation
      of lipid metabolic experiments done with microsomal fraction.

PMID- 16798075
TI  - Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and
      regulation.
AB  - Acyl-CoA synthetases (ACSs) are a family of enzymes that catalyze the
      thioesterification of fatty acids with coenzymeA to form activated intermediates,
      which play a fundamental role in lipid metabolism and homeostasis of lipid
      related processes. The products of the ACS enzyme reaction, acyl-CoAs, are
      required for complex lipid synthesis, energy production via beta-oxidation,
      protein acylation and fatty-acid dependent transcriptional regulation. ACS
      enzymes are also necessary for fatty acid import into cells by the process of
      vectorial acylation. The yeast Saccharomyces cerevisiae has four long chain ACS
      enzymes designated Faa1p through Faa4p, one very long chain ACS named Fat1p and
      one ACS, Fat2p, for which substrate specificity has not been defined. Pivotal
      roles have been defined for Faa1p and Faa4p in fatty acid import, beta-oxidation
      and transcriptional control mediated by the transcription factors Oaf1p/Pip2p and
      Mga2p/Spt23p. Fat1p is a bifunctional protein required for fatty acid transport
      of long chain fatty acids, as well as activation of very long chain fatty acids.
      This review focuses on the various roles yeast ACS enzymes play in cellular
      metabolism targeting especially the functions of specific isoforms in fatty acid
      transport, metabolism and energy production. We will also present evidence from
      directed experimentation, as well as information obtained by mining the molecular
      biological databases suggesting the long chain ACS enzymes are required in
      protein acylation, vesicular trafficking, signal transduction pathways and cell
      wall synthesis.

PMID- 16798076
TI  - Overexpression of SND p102, a rat homologue of p100 coactivator, promotes the
      secretion of lipoprotein phospholipids in primary hepatocytes.
AB  - SND p102 belongs to an evolutionarily conserved family of proteins first
      described as transcriptional coactivators, whose biological function has not yet
      been defined. High expression levels of homologues of SND p102 in non-nuclear
      compartments of lipid secretory tissues and in murine liver endoplasmic reticulum
      suggest a role for SND p102 in lipoprotein secretion in hepatocytes. To address
      this issue, after ascribing by confocal microscopy and Western blotting a non
      nuclear localization of SND p102 in rat hepatocytes, we cloned its full-length
      cDNA, developed adenoviral vectors encoding the cDNA or a specific antisense
      sequence, and characterized the lipoprotein particles created and released for 24
      h by transfected rat hepatocytes. The cellular ability to secrete apoB and apoA-I
      was not affected by SND p102 differential expression, nor was that of
      lipoproteins-triglyceride, -cholesterol and -cholesteryl esters. However, cells
      overexpressing SND p102 secreted phospholipid-rich lipoproteins. Compared with
      hepatocytes with basal or attenuated SND p102 expression, they secreted
      approximately 45% and 80% more phospholipid in d<1.015 g/mL and 1.015<d<1.24 g/mL
      lipoproteins, respectively. Oversecretion affected all phospholipid classes and
      did not significantly disturb the cellular phospholipid homeostasis.
      Collectively, the results suggest a specific, positive association of SND p102
      and phospholipid release in lipoprotein particles in hepatocytes.

PMID- 16798077
TI  - The frequency of ulnar to median nerve anastomosis (Marinacci communication).

PMID- 16798078
TI  - Inhibition, conflict and the Nogo-N2.

PMID- 16798079
TI  - Is diabetic dermopathy a sign for severe neuropathy in patients with diabetes
      mellitus? Nerve conduction studies and symptom analysis.
AB  - OBJECTIVE: To assess if diabetic dermopathy (DD) is a sign for severe
      polyneuropathy (PNP). METHODS: We investigated the clinical and
      electrophysiological characteristics of 166 diabetic men (59.5+11.1 years) with
      different degrees of peripheral nerve involvement. RESULTS: All of the clinical
      variables were more common in patients with diabetic foot ulcers (DF) than in
      patients with sole PNP (P<0.001). Only the loss of superficial and vibration
      sense was more common in the DF patients than the DD patients (P<0.02). Nerve
      conduction studies showed the mean compound muscle action potentials (CMAP) were
      smaller in the DD and DF patients than the PNP patients for peroneal, median and
      ulnar nerves (P<0.01). The mean nerve conduction velocities (NCV) of all nerves
      were slower in the DD and DF patients in compared to sole PNP patients (P<0.01).
      The mean distal latencies (DL) of the DD/DF patients were longer than the PNP
      group. CONCLUSIONS: The DD and DF patients did not significantly differ in CMAP,
      NCV, and DL. SIGNIFICANCE: Both clinical and electrophysiological features of DD
      and DF are similar, and significant different than PNP alone. These results
      suggest that DD is an important clinical sign for more severe neuropathic
      impairment.

PMID- 16798080
TI  - Mobile phone artifact.

PMID- 16798081
TI  - Higher anticipated force required a stronger inhibitory process in go/nogo tasks.
AB  - OBJECTIVE: We investigated the effect of the inhibitory process with increasing
      muscle force on event-related potentials (ERPs) and motor evoked potentials
      (MEPs). METHODS: The subjects performed a S1-S2 paradigm with go/nogo tasks. S1
      was an auditory tone burst, and S2 was an electrical stimulation applied to the
      second (go stimuli) or fifth digit (nogo stimuli) of the left hand. The
      recordings were conducted at 3 force levels; 10, 30 and 50% maximal voluntary
      contraction (MVC). After the presentation of S2, the subjects were instructed to
      adjust their force level to match the target line with a force trajectory line in
      only the go trials. RESULTS: Nogo-N140 was significantly more negative in
      amplitude than go-N140 in all conditions, and became larger with increasing
      muscle force. The MEP, which was recorded at 150 ms after S2, became
      significantly smaller with increasing muscle force in nogo trials, whereas it
      became larger in go trials. CONCLUSIONS: Our results indicated that stronger
      inhibitory cerebral activity was needed for a nogo stimulus, in the case where a
      stronger response was needed for a go stimulus. SIGNIFICANCE: The present study
      showed a significant relationship between cortical inhibitory process and muscle
      force.

PMID- 16798082
TI  - Spike orientation may predict epileptogenic side across cerebral sulci containing
      the estimated equivalent dipole.
AB  - OBJECTIVE: To evaluate whether the orientation of interictal spikes, localized in
      major sulci by magnetoencephalography (MEG), predicts the epileptogenic side of
      the sulcal wall. METHODS: Sixteen epilepsy patients were analyzed in whom
      equivalent current dipoles (ECDs) of MEG spikes were localized on the central
      (four patients), interhemispheric (4), or sylvian fissure (8); and the
      epileptogenic side across the sulci had been confirmed by seizure semiology,
      structural lesions, or intracranial electroencephalography (EEG). ECD was
      classified as epileptogenic side or normal side oriented and correlated to the
      scalp EEG map. RESULTS: All central (n=50) and interhemispheric (n=83) spike ECDs
      were oriented toward the epileptogenic side at peak latency. In scalp EEG, 91% of
      the spikes showed radial pattern of broad negativity above the sulcus whereas 9%
      showed tangential pattern with positive maximum above the epileptogenic side.
      Sylvian spikes were only found in patients with temporal lobe epilepsy (TLE). In
      sylvian spikes (n=220), 73% of ECDs were oriented toward the epileptogenic side,
      whereas 27% were oriented toward the normal side. CONCLUSIONS: In central and
      interhemispheric spikes, epileptogenic side cortex may be gross surface negative
      through the sulcal wall to the adjacent gyrus. Inconsistent orientation of the
      sylvian spikes suggests a complex pattern of spike propagation in TLE.
      SIGNIFICANCE: ECD orientation of central and interhemispheric spikes in MEG may
      predict the epileptogenic side.

PMID- 16798083
TI  - Auditory steady-state evoked potentials (ASSEPs): a study of optimal stimulation
      parameters for frequency-specific threshold measurement in dogs.
AB  - OBJECTIVE: To define the optimal stimulation parameters (AM/FM vs AM alone and
      modulation rate) for frequency-specific threshold measurements using ASSEPs in
      dogs. Dependent variables were thresholds and recording times needed to obtain a
      response at threshold. To compare the ASSEP threshold results obtained with the
      optimal stimulation parameters to those obtained with the Tone-Burst/Auditory
      Brainstem Response (TB/ABR) combination. METHODS: Thirty-two sedated Beagle
      puppies were tested at 5 audiometric frequencies (0.5-8 kHz) and 6 ASSEP
      modulation rates (21-199 Hz). RESULTS: The ASSEP threshold-modulation rate
      functions had a high-pass profile with corner frequencies of 101 Hz for 0.5, 1
      and 2 kHz carriers and of 151 Hz for 4 and 8 kHz carriers. AM stimuli did not
      yield higher thresholds than the AM/FM ones except at 1 kHz. Modulation type had
      no effect on testing duration. Audiometric profiles were obtained much more
      rapidly with ASSEPs than with TB/ABRs (mean: 50 vs 135 min). Both ASSEP and
      TB/ABR provided thresholds estimates characterized by low intersubject
      variability. CONCLUSIONS: ASSEPs are a valid and rapid method for audiometric
      assessment in sedated dogs. SIGNIFICANCE: ASSEPs offer a new, competitive tool
      for frequency-specific assessment of hearing in the canine species.

PMID- 16798084
TI  - Meeting report: molecular ecology workshop. Detection of microbial biodiversity
      in environmental samples, Camerino, Italy, September 19-21, 2005.

PMID- 16798085
TI  - Genetic heterogeneity of urease gene loci in urease-positive thermophilic
      Campylobacter (UPTC).
AB  - Degenerate PCR primers in silico based on the two urease structural genes, ureA
      and ureB, were designed for urease-positive thermophilic Campylobacter (UPTC).
      Resultant PCR amplification employing these primers generated an amplicon of
      approximately 2kb, which was cloned and sequenced in UPTC (n=12) isolated from
      various parts of Europe and Japan. Overall, sequence similarities were shown to
      be 96.7 to 99.9%. Following sequence alignment analysis, the approximate 1.96kb
      regions were deduced to consist of parts of ureA (about 570bps) and ureB (about
      1390bps) with an overlapping region between the ureA and ureB gene loci. Although
      a total of 144 heterogeneous sites of all substitutions were located throughout
      this region, the substitution ratio was higher in the ureA region
      (1/Omega10bases) than in the ureB region (1/Omega15bases). A resulting dendrogram
      was constructed, which was based on the nucleotide sequence data of 12 UPTC
      isolates and demonstrated that the UPTC were genetically variable. They formed a
      major cluster with Helicobacter, separate from the other urease-producing
      bacteria examined, suggesting a shared ancestry between UPTC and Helicobacter.

PMID- 16798086
TI  - Stop-codon read-through for patients affected by a lysosomal storage disorder.
AB  - Lysosomal storage disorders are a group of inherited diseases that can result in
      severe and progressive pathology due to a specific lysosomal dysfunction. Current
      treatment strategies include bone-marrow transplantation, substrate reduction,
      chemical-chaperone and enzyme-replacement therapy. However, each of these
      treatments has its limitations. Enhanced stop-codon read-through is a potential
      alternative or adjunct therapeutic strategy for treating lysosomal-storage
      disorder patients. Premature stop-codon mutations have been identified in a large
      cohort of patients with a lysosomal storage disorder, making stop-codon read
      through a possible treatment for this disease. In lysosomal-storage-disorder
      cells (mucopolysaccharidosis type I, alpha-L-iduronidase deficient), preclinical
      studies have shown that gentamicin induced the read-through of premature stop
      codons, resulting in enzyme activity that reduced substrate storage.

PMID- 16798087
TI  - Targeted induction of apoptosis for cancer therapy: current progress and
      prospects.
AB  - Important breakthroughs in cancer therapy include clinical application of
      antibodies, such as Rituximab, and small inhibitory molecules, such as Iressa and
      Velcade. In addition, recent reports have indicated the therapeutic potential of
      physiological pro-apoptotic proteins such as TRAIL and galectin-1. Although
      unrelated at first glance, each strategy relies on the deliberate and selective
      induction of apoptosis in malignant cells. Importantly, therapy-resistance in
      cancer is frequently associated with de-regulation in the mechanisms that control
      apoptosis. However, cancer cells are often reliant on these molecular aberrations
      for survival. Therefore, selective induction of apoptosis in cancer cells but not
      normal cells seems feasible. Here, we review recent progress and prospects of
      selected novel anti-cancer approaches that specifically target and sensitize
      cancer cells to apoptosis.

PMID- 16798088
TI  - Reconsidering the underestimated burden caused by neglected tropical diseases.
AB  - It is generally acknowledged that the burden caused by neglected tropical
      diseases needs to be reassessed. Not only are there several important diseases
      unaccounted for, but new information suggests they have a more substantial impact
      on health than initially thought. Looking at the tropical diseases as a group
      makes sense: they tend to cluster in the same poor populations and, to make
      progress with their control, they will have to be dealt with in an integrated
      manner. Measuring the effect of such integrated control is likely to reveal the
      real impact of tropical diseases on human health and wellbeing.

PMID- 16798089
TI  - Mapping the global extent of malaria in 2005.
AB  - Guidelines for travellers on malaria chemoprophylaxis, the altitude limits of
      dominant vector species, climate suitability for malaria transmission and human
      population density thresholds have been used to map the crude spatial limits of
      Plasmodium falciparum and Plasmodium vivax transmission on a global scale. These
      maps suggest that 2.510 and 2.596 billion people were at possible risk of
      transmission of P. falciparum and P. vivax, respectively, in 2005. Globally, 75
      per cent of humans who are exposed to P. falciparum risk live in only ten
      countries.

PMID- 16798090
TI  - Worms and malaria: resisting the temptation to generalize.

PMID- 16798091
TI  - Plasma exchange in severe hypertriglyceridemia a clinical study.
AB  - BACKGROUND: Hypercholesterolemia and hypertriglyceridemia are independent risk
      factors for atherosclerotic heart diseases. Moreover acute pancreatitis may occur
      in patients with severe hypertriglyceridemia. AIM OF THE STUDY: To evaluate the
      effectiveness of plasma exchange (PE) in patients with severe
      hypertriglyceridemia. METHODS: Seven patients with severe hypertriglyceridemia (a
      triglyceride level of more than 1000mg/dl) were treated with PE. After PE, lipid
      and hematological parameters and side effects were evaluated. RESULTS:
      Triglyceride levels decreased below 1000mg/dl in all patients. The levels of
      triglyceride and very low-density lipoprotein cholesterol (p<0.05 for both), and
      total cholesterol (p<0.005) decreased significantly. PE was well-tolerated. Liver
      and renal functions, hematological parameters, except for an increase in white
      blood cell counts, did not change significantly. CONCLUSION: PE may be used
      safely and effectively in severe hyperlipidemic patients at risk of acute
      coronary events and acute pancreatitis. Further extended studies may provide more
      detailed information.

PMID- 16798092
TI  - Thrombotic thrombocytopenic purpura and systemic lupus erythematosus - distinct
      entities or overlapping syndromes?
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening
      syndrome characterized by platelet aggregation leading to occlusive
      microangiopathy. TTP has been rarely reported to simultaneously present with
      systemic lupus erythematosus (SLE). CASE: A 61-year-old male presenting with TTP
      was also concurrently diagnosed with SLE. The patient recovered only after
      combined treatments with plasmapheresis and immunosuppressive therapy.
      CONCLUSION: This case is the first to describe the simultaneous presentation of
      TTP and SLE in an elderly gentleman. While it is important to distinguish between
      the two diseases because of therapeutic implications, cases of concurrent TTP and
      SLE help to elucidate the pathophysiology that underlies each condition.

PMID- 16798094
TI  - Hydrophobic collapse in (in silico) protein folding.
AB  - A model of hydrophobic collapse, which is treated as the driving force for
      protein folding, is presented. This model is the superposition of three models
      commonly used in protein structure prediction: (1) 'oil-drop' model introduced by
      Kauzmann, (2) a lattice model introduced to decrease the number of degrees of
      freedom for structural changes and (3) a model of the formation of hydrophobic
      core as a key feature in driving the folding of proteins. These three models
      together helped to develop the idea of a fuzzy-oil-drop as a model for an
      external force field of hydrophobic character mimicking the hydrophobicity
      differentiated environment for hydrophobic collapse. All amino acids in the
      polypeptide interact pair-wise during the folding process (energy minimization
      procedure) and interact with the external hydrophobic force field defined by a
      three-dimensional Gaussian function. The value of the Gaussian function usually
      interpreted as a probability distribution is treated as a normalized
      hydrophobicity distribution, with its maximum in the center of the ellipsoid and
      decreasing proportionally with the distance versus the center. The fuzzy-oil-drop
      is elastic and changes its shape and size during the simulated folding procedure.

PMID- 16798093
TI  - MicroRNA sequence motifs reveal asymmetry between the stem arms.
AB  - The processing of micro RNAs (miRNAs) from their stemloop precursor have revealed
      asymmetry in the processing of the mature and its star sequence. Furthermore, the
      miRNA processing system between organism differ. To assess this at the sequence
      level we have investigated mature miRNAs in their genomic contexts. We have
      compared profiles of mature miRNAs within their genomic context of the 5' and 3'
      stemloop precursor arms and we find asymmetry between mature sequences of the 5'
      and 3' stemloop precursor arms. The main observation is that vertebrate organisms
      have a characteristic motif on the 5' arm which is in contrast to the 3' arm
      motif which mainly show the conserved U at the position of the mature start. Also
      the vertebrate 5' arm motif show a semi-conserved G 13 nucleotides upstream from
      the first position. We compared the 5' and 3' arm profiles using the average log
      likelihood ratio (ALLR) score, as defined by Wang and Stormo (2003) [Wang T.,
      Stormo, G.D., 2003. Combining phylogenetic data with co-regulated genes to
      identify regulatory motifs. Bioinformatics 2369-2380.] and computing a p-value we
      find that the two profiles differs significantly in their 3' end where the 5' arm
      motif (in contrast to the 3' arm motif) has a semi-conserved GU rich region.
      Similar findings are also obtained for other organisms, such as fly, worm and
      plants. The observed similarities and differences between closely and distantly
      related organisms are discussed and related to current knowledge of miRNA
      processing.

PMID- 16798095
TI  - Molecular dynamics study on the ligand recognition by tandem SH3 domains of
      p47phox, regulating NADPH oxidase activity.
AB  - The phagocyte NADPH oxidase complex plays a crucial role in host defense against
      microbial infection through the production of superoxides. Chronic granulomatous
      disease (CGD) is an inherited immune deficiency caused by the absence of certain
      components of the NADPH oxidase. Key to the activation of the NADPH oxidase is
      the cytoplasmic subunit p47phox, which includes the tandem SH3 domains (N-SH3 and
      C-SH3). In active phagocytes, p47phox forms a stable complex with the cytoplasmic
      region of membrane subunit p22phox that forms a left-handed polyproline type-II
      (PPII) helix conformation. In this report, we have analyzed the conformational
      changes of p47phox-p22phox complexes of wild-type and three mutants, which have
      been detected in CGD patients, using molecular dynamics simulations. We have
      found that in the wild-type, two basal planes of PPII prism in cytoplasmic region
      of p22phox interacted with N-SH3 and C-SH3. In contrast, in the modeled mutants,
      the residue at the ape of PPII helix, which interacts simultaneously with both of
      the tandem SH3 domains in the wild-type, moved toward C-SH3. Furthermore,
      interaction energies of the cytoplasmic region of p22phox with C-SH3 tend to
      decrease in these mutants. All these findings led us to conclude that
      interactions between N-SH3 of p47phox and PPII helix, which is formed by
      cytoplasmic region of p22phox, may play a significant role in the activation of
      the NADPH oxidase.

PMID- 16798096
TI  - Unraveling the nature of the segmentation clock: Intrinsic disorder of clock
      proteins and their interaction map.
AB  - Vertebrate segmentation has been proved to be under a strict temporal control
      governed by a biological clock, known as the segmentation clock. The present
      experimental evidence suggests that the segmentation clock initiates and
      maintains its periodic cycle by the periodic activation or inhibition of the
      Notch signaling pathway as well as the periodic autoregulation of the cyclic
      genes themselves. In this paper, we investigate the structural and evolutionary
      properties of the Notch pathway proteins involved in the mice segmentation clock
      and computationally identify the interaction map within the Notch signaling
      pathway. The results of our analysis strongly indicate that most of the pathway
      proteins are intrinsically disordered and that the mechanism of their interaction
      likely involves helical molecular recognition elements, short loosely structured
      segments within disordered regions which are directly involved in protein-protein
      interactions. Predicted interactions are in agreement with gene knock-out studies
      available in the literature.

PMID- 16798097
TI  - Evidence of a selective epitope loss of anti-transglutaminase immunoreactivity in
      gluten-free diet celiac sera: a new tool to distinguish disease-specific
      immunoreactivities.
AB  - The aim of the present study was to evaluate the epitope specific humoral human
      tissue transglutaminase (tTG) immunoreactivity against 3 different human
      recombinant tTG constructs [(full-length tTG (a.a. 1-687), tTG (a.a. 227-687);
      tTG (a.a. 473-687)] before and after the introduction of a gluten-free diet
      (GFD). To this end, sera from 64 celiac disease (CD) subjects on a gluten
      containing diet (44 f, 20 m) and after 0.6 +/- 0.3 years and 2.1 +/- 1.3 years of
      GFD were studied using a quantitative radioimmunoprecipitation assay. All 64 CD
      patients at diagnosis were full-length anti-tTG (a.a. 1-687)Ab positive. These
      Abs significantly decreased in frequency and titer after 6 months and 2 years of
      GFD. However, at low titers, 64.1% (41/64) of CD patients were still fl-tTG (a.a.
      1-687)Ab positive after 2 years of GFD. At disease diagnosis, 70.3% (45/64) of
      the CD patients had Abs directed against fragments (227-687) and/or (473-687) of
      the tTG protein. This percentage, after 2 years of GFD, significantly decreased
      to 18.7%, whereas almost 50% of GFD patients had no tTG (227-687) and tTG (473
      687) fragment reactivity, but only persistent, low-titer full-length tTG (1
      687)Abs. We suggest that the selective loss of immunoreactivity against tTG (227
      687) and tTG (473-687) fragments in CD patients with a GFD, could be due to
      quantitative decrease of autoreactivity driven by tTG-gliadin interaction
      underlying celiac disease pathogenesis.

PMID- 16798099
TI  - Nonconvulsive status epilepticus with an unusual EEG: a fresh look at
      lateralities of motor control and awareness.
AB  - This article is an account of a patient with nonconvulsive status epilepticus
      associated with an unusual EEG. The importance of recording speed in lateralizing
      the hemisphere of onset of epilepsy is emphasized, on the basis of one-way
      callosal traffic theory. From this vantage point, the following were deemed
      responsible for the currently divergent views on the lateralizing significance of
      various signs and symptoms in epilepsy: (1) the dichotomous nature of laterality
      of motor control, which is the same as that of seizure onset; (2) the
      probabilistic nature of the availability of the callosal channel for transfer of
      epileptiform discharges from the major to the minor hemisphere (i.e., the random
      variability of synaptic transfer); (3) the dynamic (varying) expanse of the
      epileptic region within the major hemisphere. Other data reviewed indicated that
      measuring the reaction time of two symmetrically located effectors is the most
      robust way of determining the laterality of the major hemisphere, with the side
      of shorter reaction time being opposite to the major hemisphere. Clinical
      presentations of seizures reflect the probabilistic involvement of different
      regions of the major hemisphere by the epileptic process and the spread of the
      epilepsy to the minor hemisphere via the callosum. Termination of seizure
      activity with diazepam was associated with simultaneous recovery of awareness and
      speech in this case.

PMID- 16798098
TI  - Effective high-capacity gutless adenoviral vectors mediate transgene expression
      in human glioma cells.
AB  - Glioblastoma multiforme (GBM) is the most common subtype of primary malignant
      brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used
      successfully in clinical trials for GBM, the capacity of Ads to infect human
      glioma cells and the expression of adenoviral receptors in GBM cells have been
      challenged. In this report, we studied the expression of three molecules that
      have been shown to mediate adenoviral entry into cells, i.e., coxsackie and
      adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major
      histocompatibility complex class I (MHCI), in rodent glioma cell lines and low
      passage primary cultures and cell lines from human GBM. We correlated levels of
      expression of CAR, INT, and MHCI with transduction efficiency elicited by several
      high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of
      adenoviral receptors were variable among the different GBM cells studied. HC-Ad
      mediated therapeutic gene expression was efficient, ranging between 20 and 80% of
      the total target cells expressing the encoded transgenes. Our results show no
      correlation between the levels of CAR, INT, or MHCI molecules and the levels of
      transgene expression or the number of GBM cells transduced. We conclude that
      expression levels of adenoviral receptors do not predict their transduction
      efficiency or biological function.

PMID- 16798100
TI  - Behavioral, social, and affective factors associated with self-efficacy for self
      management among people with epilepsy.
AB  - The purpose of the study described in this article was to evaluate the extent to
      which selected behavioral, social, and affective factors contribute to self
      reported epilepsy self-efficacy. Participants completed three assessments 3
      months apart, with only those completing both the first and second assessments
      included in this analysis. Self-efficacy scores at the second assessment were
      regressed on the behavioral, social, and affective characteristics ascertained at
      the first assessment. The analysis revealed that self-management, depressive
      symptoms, and seizure severity explain the most variance in self-efficacy;
      patient satisfaction and stigma are less important predictors; and social support
      and regimen-specific support are not significant predictors. The results provide
      direction for identifying people with low levels of self-efficacy and
      highlighting areas that might help enhance self-efficacy in persons with
      epilepsy.

PMID- 16798101
TI  - Long term clinical trials: how much information do participants retain from the
      informed consent process?
AB  - Previous studies report mixed results about how much information study
      participants actually can read, understand and retain after completing the
      informed consent process; fewer studies have examined disparities in the
      retention and recall of information by patient factors, such as age, education,
      and race. Not retaining or being able to recall information from the informed
      consent process has potentially important ethical and legal implications and
      consequences for research quality and integrity, especially when found in
      populations that commonly are underserved or underrepresented in clinical trials.
      To determine how much basic knowledge participants finishing a five-year, multi
      center, double-blinded randomized, placebo-controlled clinical trial had about
      the study, participants (n=1,789) were asked at their final follow-up visit three
      multiple-choice questions: (1) the study's purpose; (2) the name of the
      medication under investigation; (3) the main side effect of the medication. The
      associations between knowledge of these fundamental details and participant
      social and demographic factors were investigated. A majority of participants
      correctly recalled the study's purpose (64.7%) and medication (79.6%), but few
      correctly reported the main side effect (31.1%). In spite of relatively high
      recall for study purpose and medication, disparities by age, education and race
      exist. Increasing age was significantly associated with higher odds of
      incorrectly recalling both the study purpose and the name of the study
      medication. Likewise those with less than a high school education were more
      likely to incorrectly identify the study's purpose and the name of the study
      medication. Black and other non-white race or ethnic groups were more than two
      and a half times as likely to incorrectly identify the study's purpose. These
      findings suggest that even the most basic information may not be understood or
      retained by important subgroups of patients enrolled in clinical trials.
      Implementing effective strategies, such as additional time and effort for consent
      or repetition of study information, may be necessary in order to assure ethical
      and valid consent.

PMID- 16798102
TI  - The organisation of the autonomic nervous system: peripheral connections.

PMID- 16798103
TI  - Mixed cranial nerve neuroma revealing itself as baroreflex failure.
AB  - We report here the first case of baroreflex failure due to a mixed cranial nerve
      neuroma in which the clinical manifestations (recurrent severe hypertensive
      crisis, hypotension) due to baroreflex arc impairment preceded the clinical
      diagnosis of brain tumour and neurosurgery by a few months. Given the clinical
      suspicion of baroreflex failure, even in the absence of iatrogenic clues, we
      propose that the patient's study should include neuroradiologic evaluation of the
      ponto-cerebellar angulus.

PMID- 16798104
TI  - Effects of carvedilol on M2 receptors and cholinesterase-positive nerves in
      adriamycin-induced rat failing heart.
AB  - Heart failure is correlated with attenuation of parasympathetic nervous function
      and enhanced sympathetic activity. Carvedilol, a third-generation beta-blocker,
      may improve the prognosis of heart failure better than selective beta(1)
      blockers. Not all of its effects, however, can be explained by direct actions on
      the sympathetic nervous system. This study was therefore performed to investigate
      the possible alterations of muscarinic cholinergic (M)(2) receptors and
      cholinesterase-positive nerves in different regions of the adriamycin-induced
      failing rat heart, and the potential effects of carvedilol on these M(2)
      receptors and cholinesterase-positive nerves. Karnovsky-Roots histochemical
      staining combined with point counting methods, and immunochemical streptavidin
      biotin complex staining and image analysis were used to test the distribution of
      cholinesterase-positive nerves and the expression of M(2) receptors,
      respectively. Our results show that the cholinesterase-positive nerve system was
      downregulated in the adriamycin-induced failing heart group, while the density of
      M(2) receptors was increased in the carvedilol 3- and 10-mg/kg body weight
      groups, especially in the endocardial tissues of the left-ventricular free wall.
      It is concluded that upregulation of M(2) receptors may be one of the potential
      mechanisms by which carvedilol exert its action on heart failure.

PMID- 16798105
TI  - Lung specific developmental expression of the Xenopus laevis surfactant protein C
      and B genes.
AB  - Efforts to characterize the mechanisms underlying early lung development have
      been confounded by the absence of a model that permits study of lung development
      prior to the onset of endodermal differentiation. Since Xenopus laevis
      development occurs in an extrauterine environment, we sought to determine whether
      the classical molecular markers of lung development and function, surfactant
      protein genes, are expressed in X. laevis. Surfactant protein C (SP-C) is a
      specific marker for lung development, expressed early in development and
      exclusively in the lung. Surfactant protein B (SP-B) expression is essential for
      life, as its absence results in neonatal death in mice and gene mutations have
      been associated with neonatal respiratory failure in humans. Here, we report the
      cloning of the first non-mammalian SP-C and SP-B genes (termed xSP-C and xSP-B)
      using the Xenopus model. The processed mature translated regions of both xSP-C
      and xSP-B have high homology with both human and mouse genes. xSP-C and xSP-B are
      both expressed throughout the lung of the X. laevis swimming tadpoles soon after
      the initiation of lung development as assessed by RT-PCR and whole mount in situ
      hybridization. The temporal expression patterns of xSP-C and xSP-B are consistent
      with the expression patterns in mammalian models of lung development. In both the
      tadpole and the adult X. laevis, xSP-C and xSP-B are expressed only in lung.
      Knowledge of the sequence and expression pattern of these two surfactant proteins
      in Xenopus might allow for use of this organism to study early lung development.

PMID- 16798106
TI  - Fgf19 expression patterns in the developing chick inner ear.
AB  - The inner ear is a complex sensorial structure with hearing and balance
      functions. A key aim of developmental biology is to understand the molecular and
      cellular mechanisms involved in the induction, patterning and innervation of the
      vertebrate inner ear. These developmental events could be mediated by the
      expression of regulating genes, such as the members of the family of Fibroblast
      Growth Factors (Fgfs). This work reports the detailed spatial and temporal
      patterns of Fgf19 expression in the developing inner ear from otic cup (stage 14)
      to 8 embryonic days (stage 34). In the earliest stages, Fgf19 and Fgf8
      expressions determine two subdomains within the Fgf10-positive proneural-sensory
      territory. We show that, from the earliest stages, the Fgf19 expression was
      detected in the acoustic-vestibular ganglion and the macula utriculi. The Fgf19
      gene was also strongly, but transiently, expressed in the macula lagena, whereas
      the macula neglecta never expressed this gene in the period analysed. The Fgf19
      expression was also clearly observed in some borders of various sensory elements.
      These results could be useful from further investigations into the role of FGF19
      in otic patterning.

PMID- 16798107
TI  - Regulation of spblimp1/krox1a, an alternatively transcribed isoform expressed in
      midgut and hindgut of the sea urchin gastrula.
AB  - The sea urchin regulatory gene Spblimp1/krox produces alternatively transcribed
      and spliced isoforms, 1a and 1b, which have different temporal and spatial
      patterns of expression. Here we describe a cis-regulatory module that controls
      the expression of the 1a splice form in the midgut and hindgut at the beginning
      of gastrulation. Conserved sequence patches revealed by a comparison of the
      blimp1/krox locus in Strongylocentrotus purpuratus and Lytechinus variegatus
      genomes were tested by gene transfer, in association with GFP or CAT reporter
      genes. An expression construct containing a conserved sequence patch immediately
      5' of exon 1a included the transcription initiation site for blimp1/krox1a. This
      construct displays specific mid and hindgut expression, indicating that these are
      the locations of endogenous blimp1/krox1a transcription during the gastrula
      stage. Its sequence contains binding sites for Brn1/2/4, Otx, and Blimp1/Krox
      itself, as predicted in a prior regulatory network analysis.

PMID- 16798109
TI  - The role of DNA damage response proteins at telomeres--an "integrative" model.
AB  - Telomeres are specialized structures at chromosome ends which play the key role
      in chromosomal end protection. There is increasing evidence that many DNA damage
      response proteins are involved in telomere maintenance. For example, cells
      defective in DNA double strand break repair proteins including Ku, DNA-PKcs,
      RAD51D and the MRN (MRE11/RAD51/NBS1) complex show loss of telomere capping
      function. Similarly, mouse and human cells defective in ataxia telangiectasia
      mutated (ATM) have defective telomeres. A total of 14 mammalian DNA damage
      response proteins have, so far, been implicated in telomere maintenance. Recent
      studies indicate that three more proteins, namely BRCA1, hRad9 and PARP1 are
      involved in telomere maintenance. The involvement of a wide range of DNA damage
      response proteins at telomeres raises an important question: do telomere
      maintenance mechanisms constitute an integral part of DNA damage response
      machinery? A model termed the "integrative" model is proposed here to argue in
      favour of telomere maintenance being an integral part of DNA damage response. The
      "integrative" model is supported by the observation that a telomeric protein,
      TRF2, is not confined to its local telomeric environment but it migrates to the
      sites of DNA breakage following exposure of cells to ionizing radiation.
      Furthermore, even if telomeres are maintained in a non-canonical way, as in the
      case of Drosophila, DNA damage response proteins are still involved in telomere
      maintenance suggesting integration of telomere maintenance mechanisms into the
      DNA damage response network.

PMID- 16798110
TI  - Recombinase, chromosomal translocations and lymphoid neoplasia: targeting
      mistakes and repair failures.
AB  - A large number of lymphoid malignancies is characterized by specific chromosomal
      translocations, which are closely linked to the initial steps of pathogenesis.
      The hallmark of these translocations is the ectopic activation of a silent proto
      oncogene through its relocation at the vicinity of an active regulatory element.
      Due to the unique feature of lymphoid cells to somatically rearrange and mutate
      receptor genes, and to the corresponding strong activity of the immune
      enhancers/promoters at that stage of cell development, B- and T-cell
      differentiation pathways represent propitious targets for chromosomal
      translocations and oncogene activation. Recent progress in the understanding of
      the V(D)J recombination process has allowed a more accurate definition of the
      translocation mechanisms involved, and has revealed that V(D)J-mediated
      translocations result both from targeting mistakes of the recombinase, and from
      illegitimate repair of the V(D)J recombination intermediates. Surprisingly, V(D)J
      mediated translocations turn out to be restricted to two specific sub-types of
      lymphoid malignancies, T-cell acute lymphoblastic leukemias, and a restricted set
      of mature B-cell Non-Hodgkin's lymphomas.

PMID- 16798111
TI  - Adenovirus mediated transduction of the human DNA polymerase eta cDNA.
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disorder with
      an extremely high incidence of skin cancers. Seven complementation groups,
      corresponding to seven proteins involved in nucleotide excision repair (NER), are
      associated with this syndrome. However, in XP variant patients, the disorder is
      caused by defects in DNA polymerase eta; this error prone polymerase, encoded by
      POLH, is involved in translesion DNA synthesis (TLS) on DNA templates damaged by
      ultraviolet light (UV). We constructed a recombinant adenovirus carrying the
      human POLH cDNA linked to the EGFP reporter gene (AdXPV-EGFP) and infected skin
      fibroblasts from both XPV and XPA patients. Twenty-four hours after infection,
      the DNA polymerase eta-EGFP fusion protein was detected by Western blot analysis,
      demonstrating successful transduction by the adenoviral vector. Protein
      expression was accompanied by reduction in the high sensitivity of XPV cells to
      UV, as determined by cell survival and apoptosis-induction assays. Moreover, the
      pronounced UV-induced inhibition of DNA synthesis in XPV cells and their arrest
      in S phase were attenuated in AdXPV-EGFP infected cells, confirming that the
      transduced polymerase was functional. However, over-expression of polymerase eta
      mediated by AdXPV-EGFP infection did not result in enhancement of cell survival,
      prevention of apoptosis, or higher rate of nascent DNA strand growth in
      irradiated XPA cells. These results suggest that TLS by DNA polymerase eta is not
      a limiting factor for recovery from cellular responses induced by UV in excision
      repair deficient fibroblasts.

PMID- 16798112
TI  - DNA double-strand break repair and chromosome translocations.
AB  - Translocations are genetic aberrations that occur when a broken fragment of a
      chromosome is erroneously rejoined to another chromosome. The initial event in
      the creation of a translocation is the formation of a DNA double-strand break
      (DSB), which can be induced both under physiological situations, such as during
      the development of the immune system, or by exogenous DNA damaging agents. Two
      major repair pathways exist in cells that repair DSBs as they arise, namely
      homologous recombination, and non-homologous end-joining. In some situations
      these pathways can function inappropriately and rejoin ends incorrectly to
      produce genomic rearrangements, including translocations. Translocations have
      been implicated in cancer because of their ability to activate oncogenes. Due to
      selection at the level of the DNA, the cell, and the tissue certain forms of
      cancer are associated with specific translocations that can be used as a tool for
      diagnosis and prognosis of these cancers.

PMID- 16798113
TI  - Recombination between retrotransposons as a source of chromosome rearrangements
      in the yeast Saccharomyces cerevisiae.
AB  - Homologous recombination between dispersed repeated genetic elements is an
      important source of genetic variation. In this review, we discuss chromosome
      rearrangements that are a consequence of homologous recombination between
      transposable elements in the yeast Saccharomyces cerevisiae. The review will be
      divided into five sections: (1) Introduction (mechanisms of homologous
      recombination involving ectopic repeats), (2) Spontaneous chromosome
      rearrangements in wild-type yeast cells, (3) Chromosome rearrangements induced by
      low DNA polymerase, mutagenic agents or mutations in genes affecting genome
      stability, (4) Recombination between retrotransposons as a mechanism of genome
      evolution, and (5) Important unanswered questions about homologous recombination
      between retrotransposons. This review complements several others [S. Liebman, S.
      Picologlou, Recombination associated with yeast retrotransposons, in: Y. Koltin,
      M.J. Leibowitz (Eds.), Viruses of Fungi and Simple Eukaryotes, Marcel Dekker
      Inc., New York, 1988, pp. 63-89; P. Lesage, A.L. Todeschini, Happy together: the
      life and times of Ty retrotransposons and their hosts, Cytogenet. Genome Res. 110
      (2005) 70-90; D.J. Garfinkel, Genome evolution mediated by Ty elements in
      Saccharomyces, Cytogenet. Genome Res. 110 (2005) 63-69] that discuss genomic
      rearrangements involving Ty elements.

PMID- 16798114
TI  - Elevated hepatic SULT1E1 activity in mouse models of cystic fibrosis alters the
      regulation of estrogen responsive proteins.
AB  - BACKGROUND: Previous studies with cystic fibrosis transmembrane conductance
      regulator (CFTR) DeltaF508 mice indicate that estrogen levels may play a role in
      the occurrence or severity of CF-associated liver disease. However, the
      underlying mechanisms of liver disease in CF are poorly understood. METHODS: The
      levels of SULT1E1 (estrogen sulfotransferase) were measured in livers of control
      and CFTR-knockout (KO) mice. The impact of increased SULT1E1 activity on hepatic
      protein expression was assessed by immunoblot and MALDI mass spectrometric
      analysis. RESULTS: SULT1E1 expression was significantly elevated in livers of
      several CFTR-KO mice. SULT1E1 and CFTR were specifically detected in hepatocytes
      and cholangiocytes, respectively. Elevated SULT1E1 activity may result in lower
      levels of free beta-estradiol thereby altering estrogen-responsive hepatic
      protein expression. Estrogen receptors (ER)-alpha and beta were differentially
      regulated in CFTR-KO and CFTR-DeltaF508 mice. ERalpha expression was reduced in
      mice with high SULT1E1 activity. Glutathione S-transferase-P1 and carbonic
      anhydrase III were significantly decreased in CFTR (-/-) mice with high SULT1E1
      activity. Furthermore, cytochrome P450 2B9, also estrogen regulated, was
      significantly induced in the livers of CFTR (-/-) mice with high SULT1E1
      activity. CONCLUSIONS: Elevated SULT1E1 levels and associated alterations in
      estrogen-regulated hepatic protein expression may play an important role in CF
      liver disease.

PMID- 16798115
TI  - Stability studies of amphetamine and ephedrine derivatives in urine.
AB  - Knowledge of the stability of drugs in biological specimens is a critical
      consideration for the interpretation of analytical results. Identification of
      proper storage conditions has been a matter of concern for most toxicology
      laboratories (both clinical and forensic), and the stability of drugs of abuse
      has been extensively studied. This concern should be extended to other areas of
      analytical chemistry like antidoping control. In this work, the stability of
      ephedrine derivatives (ephedrine, norephedrine, methylephedrine, pseudoephedrine,
      and norpseudoephedrine), and amphetamine derivatives (amphetamine,
      methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4
      methylenedioxymethamphetamine (MDMA)) in urine has been studied. Spiked urine
      samples were prepared for stability testing. Urine samples were quantified by
      GC/NPD or GC/MS. The homogeneity of each batch of sample was verified before
      starting the stability study. The stability of analytes was evaluated in
      sterilized and non-sterilized urine samples at different storage conditions. For
      long-term stability testing, analyte concentration in urine stored at 4 degrees C
      and -20 degrees C was determined at different time intervals for 24 months for
      sterile urine samples, and for 6 months for non-sterile samples. For short-term
      stability testing, analyte concentration was evaluated in liquid urine stored at
      37 degrees C for 7 days. The effect of repeated freezing (at -20 degrees C) and
      thawing (at room temperature) was also studied in sterile urine for up to three
      cycles. No significant loss of the analytes under study was observed at any of
      the investigated conditions. These results show the feasibility of preparing
      reference materials containing ephedrine and amphetamine derivatives to be used
      for quality control purposes.

PMID- 16798116
TI  - Liquid chromatography-electrospray mass spectrometry determination of ibogaine
      and noribogaine in human plasma and whole blood. Application to a poisoning
      involving Tabernanthe iboga root.
AB  - A liquid chromatography/electrospray ionization mass spectrometry (LC-ESI-MS)
      method was developed for the first time for the determination of ibogaine and
      noribogaine in human plasma and whole blood. The method involved solid phase
      extraction of the compounds and the internal standard (fluorescein) from the two
      matrices using OasisHLB columns. LC separation was performed on a Zorbax eclipse
      XD8 C8 column (5 microm) with a mobile phase of acetonitrile containing 0.02%
      (v/v) trimethylamine and 2mM ammonium formate buffer. MS data were acquired in
      single ion monitoring mode at m/z 311.2, 297.2 and 332.5 for ibogaine,
      noribogaine and fluorescein, respectively. The drug/internal standard peak area
      ratios were linked via a quadratic relationship to plasma (0.89-179 microg/l for
      ibogaine; 1-200 microg/l for noribogaine) and to whole blood concentrations (1.78
      358 microg/kg for ibogaine; 2-400 microg/kg for noribogaine). Precision ranged
      from 4.5 to 13% and accuracy was 89-102%. Dilution of the samples had no
      influence on the performance of the method. Extraction recoveries were > or =94%
      in plasma and > or =57% in whole blood. The lower limits of quantitation were
      0.89 microg/l for ibogaine and 1 microg/l for noribogaine in plasma, and 1.78
      microg/kg for ibogaine and 2 microg/kg for noribogaine in whole blood. In frozen
      plasma samples, the two drugs were stable for at least 1 year. In blood, ibogaine
      and noribogaine were stable for 4h at 4 degrees C and 20 degrees C and 2 months
      at -20 degrees C. The method was successfully used for the analysis of a
      poisoning involving Tabernanthe iboga root.

PMID- 16798118
TI  - Simultaneous determination of fluvoxamine isomers and quetiapine in human plasma
      by means of high-performance liquid chromatography.
AB  - An original HPLC-UV method has been developed for the simultaneous determination
      of the atypical antipsychotic quetiapine and the geometric isomers of the second
      generation antidepressant fluvoxamine. The analytes were separated on a reversed
      phase C8 column (150 mm x 4.6mm i.d., 5 microm) using a mobile phase composed of
      acetonitrile (30%) and a 10.5mM, pH 3.5 phosphate buffer containing 0.12%
      triethylamine (70%). The flow rate was 1.2 mL min(-1) and the detection
      wavelength was 245 nm. Sample pretreatment was carried out by an original solid
      phase extraction procedure using mixed-mode cation exchange (DSC-MCAX)
      cartridges; only 300 microL of plasma were needed for one analysis. Citalopram
      was used as the internal standard. The method was validated in terms of
      linearity, extraction yield, precision and accuracy. Good linearity was obtained
      in plasma over the 5.0-160.0 ng mL(-1) concentration range for each fluvoxamine
      isomer and over the 2.5-400.0 ng mL(-1) concentration range for quetiapine.
      Extraction yield values were always higher than 93%, with precision (expressed as
      relative standard deviation values) better than 4.0%. The method was successfully
      applied to human plasma samples drawn from patients undergoing polypharmacy with
      the two drugs. Satisfactory accuracy values were obtained, with mean recovery
      higher than 94%.

PMID- 16798117
TI  - Analysis of hydrolytic activity of phospholipase Calpha from porcine retina on
      retinyl ester and phosphatidylcholine using non-denaturing two-dimensional
      electrophoresis and mass spectrometry.
AB  - Hydrolysis of retinyl esters and phospholipids is important for visual functions
      of the animal retina. This study aimed to examine hydrolytic activity of an
      enzyme with native substrates such as retinyl esters and phospholipids
      responsible for this function in porcine retina. After cytosolic proteins were
      extracted from porcine retina, the proteins were separated using non-denaturing
      two-dimensional electrophoresis (2DE). Some major proteins and phospholipase
      Calpha were identified by matrix-assisted laser desorption ionisation-time of
      flight-mass spectrometry (MALDI-TOF-MS) or electrospray ionisation-tandem mass
      spectrometry (ESI-MS/MS). The phospholipase Calpha showed hydrolytic activities
      with not only alpha-naphtyl acetate but also with retinyl palmitate and
      phosphatidylcholine when effects of different substrates were investigated using
      enzyme activity staining on 2DE or MALDI-TOF-MS. Results indicated that
      hydrolytic activity of the enzyme with non-native and native substrates could be
      examined using a combination of non-denaturing 2DE and MALDI-TOF-MS.

PMID- 16798119
TI  - Quantitative determination of forty-eight antidepressants and antipsychotics in
      human serum by HPLC tandem mass spectrometry: a multi-level, single-sample
      approach.
AB  - This method describes the simultaneous determination of amisulpride,
      amitriptyline, aripiprazole, benperidol, chlorpromazine, chlorprothixene,
      citalopram, clomipramine, clozapine, desipramine, doxepin, fluoxetine,
      flupentixol, fluphenazine, fluvoxamine, haloperidol, hydroxyrisperidone,
      imipramine, levomepromazine, maprotiline, mianserine, mirtazapine, moclobemide,
      norclomipramine, nordoxepin, norfluoxetine, nortriptyline, O
      desmethylvenlafaxine, olanzapine, opipramol, paroxetine, perazine, perphenazine,
      pimozide, pipamperone, quetiapine, reboxetine, risperidone, sertraline,
      sulpiride, thioridazine, trazodone, trimipramine, venlafaxine, viloxazine,
      ziprasidone, zotepine and zuclopenthixol with a single sample/triple injection
      approach. Drugs were assigned to subgroups covering low, medium and high
      concentrations (overall range of therapeutic levels to be considered: 0.5-2000
      ng/mL) by further dilution of the supernatant obtained after the first protein
      precipitation. Chromatographic separation was necessary for isobaric mass
      fragments and performed on a monolithic C18 column (50mmx4.6mm) with methanol
      gradient and 5mM acetate buffer at pH 3.9. The injection interval was 8 min. A
      set of three internal standards was used for quantification of drugs with widely
      varying hydrophobicity. After electrospray ionization positive ion fragments were
      detected in the multiple reaction monitoring (MRM) mode with an API 4000 tandem
      mass spectrometer. Regression parameters of calibration curves and limits of
      quantification showed good covering of therapeutic and subtherapeutic ranges with
      an average correlation coefficient of 0.9988. Imprecision and inaccuracy measures
      were prepared for intra- and inter-assay comparisons at three concentration
      ranges in all subgroups. Average coefficients of variation were 6.1% for intra
      assay and 7.4% for inter-assay comparisons, while average deviations from spiked
      concentrations were 4.8% for intra-assay and 4.2% for inter-assay comparisons,
      respectively. Recovery rates, measured as the percent recoveries of spiked serum
      samples against standard solutions without serum matrix, varied between 92 and
      111%, with an average of 101%. As the only exception, the olanzapine response was
      much higher (185%) in serum matrix than in matrix-free controls.

PMID- 16798120
TI  - Small protein biomarkers of culture in Bacillus spores detected using capillary
      liquid chromatography coupled with matrix assisted laser desorption/ionization
      mass spectrometry.
AB  - Capillary liquid chromatography (cLC) coupled with matrix-assisted laser
      desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) was used
      to compare small proteins and peptides extracted from Bacillus subtilis spores
      grown on four different media. A single, efficient protein separation, compatible
      with MALDI-MS analysis, was employed to reduce competitive ionization between
      proteins, and thus interrogate more proteins than possible using direct MALDI-MS.
      The MALDI-MS data files for each fraction are assembled as two-dimensional data
      sets of retention time and mass information. This method of visualizing small
      protein data required careful attention to background correction as well as mass
      and retention time variability. The resulting data sets were used to create
      comparative displays of differences in protein profiles between different spore
      preparations. Protein differences were found between two different solid media in
      both phase bright and phase dark spore phenotype. The protein differences between
      two different liquid media were also examined. As an extension of this method, we
      have demonstrated that candidate protein biomarkers can be trypsin digested to
      provide identifying peptide fragment information following the cLC-MALDI
      experiment. We have demonstrated this method on two markers and utilized acid
      breakdown information to identify one additional marker for this organism. The
      resulting method can be used to identify discriminating proteins as potential
      biomarkers of growth media, which might ultimately be used for source
      attribution.

PMID- 16798121
TI  - Diagnosing AICA-ribosiduria by capillary electrophoresis.
AB  - AICA-ribosiduria is a recently discovered inherited metabolic disease caused by a
      defect in final steps of purine de novo biosynthesis-5-amino-4
      imidazolecarboxamide ribotide (AICAR)-transformylase/inosinemonophosphate (IMP)
      cyclohydrolase (ATIC). A rapid and selective capillary electrophoretic method for
      screening of patients with AICA-ribosiduria is described. The method is based on
      direct ultraviolet detection of 5-amino-4-imidazolecarboxamide (AICA) and 5-amino
      4-imidazolecarboxamide riboside (AICAr) in untreated urine. Background
      electrolyte consists of 100mM malonic acid adjusted with gamma-aminobutyric acid
      (pH 2.7). Under the given separation conditions both compounds of interest are
      well separated from other substances with separation efficiency of 1020000 and
      130000 theoretical plates/m for AICA and AICAr, respectively. Total analysis time
      is 3 min with the limits of detection of 3.6 microM and 4.5 microM for AICA and
      AICAr, respectively. The usefulness of the presented method for screening of
      patients with ATIC deficiency is demonstrated on samples of Chinese hamster ovary
      cell line defective in ATIC activity, spiked urine samples and urine samples from
      patients treated with high-dose MTX which do not excrete increased amounts of
      AICA and AICAr compared to untreated controls (p<0.05). The described method is
      fast and effective enough for diagnostic applications.

PMID- 16798122
TI  - A rapid and sensitive method for determination of sorafenib in human plasma using
      a liquid chromatography/tandem mass spectrometry assay.
AB  - A rapid, sensitive and specific method was developed and validated using LC/MS/MS
      for determination of sorafenib in human plasma. Sample preparation involved a
      single protein precipitation step by the addition of 0.1 mL of plasma with 0.5 mL
      acetonitrile. Analysis of the compounds of interest including the internal
      standard ([(2)H(3)(15)N] sorafenib) was achieved on a Waters X-Terra C(18) (150
      mm x 2.1mm i.d., 3.5 microm) analytical column using a mobile phase consisting of
      acetonitrile/10 mM ammonium acetate (65:35, v/v) containing 0.1% formic acid and
      isocratic flow at 0.2 mL/min for 6 min. The analytes were monitored by tandem
      mass spectrometry with electrospray positive ionization. Linear calibration
      curves were generated over the range of 7.3-7260 ng/mL for the human plasma
      samples with values for the coefficient of determination of >0.96. The values for
      both within day and between day precision and accuracy were well within the
      generally accepted criteria for analytical methods (<15%).

PMID- 16798123
TI  - High-performance anion-exchange chromatography using on-line electrolytic eluent
      generation for the determination of more than 25 intermediates from energy
      metabolism of mammalian cells in culture.
AB  - In this work, we present an improved method for the determination of a wide range
      of intracellular metabolites from mammalian cells by anion-exchange
      chromatography. The analysis includes the measurement of intermediates from
      glycolysis and tricarboxylic acid cycle as well as several additional nucleotides
      and sugar nucleotides. The use of an electrolytic on-line eluent generation
      device made the method highly convenient, reliable and prone to errors. Due to
      short delay times of the eluent generator, rapid KOH gradient changes could be
      applied to improve separation and to speed up elution. Suppressed conductivity
      and UV in series was used for detection. The detection wavelength of the UV
      detector was switched from 220 to 260 nm during the elution for a more selective
      signal depending on the absorption of analytes. Standards from more than 50
      metabolites of major cellular pathways were chromatographically tested and
      compared to chromatograms from extraction samples of Madin-Darby canine kidney
      (MDCK) and BHK21 cells. A validation for most substances was performed. Detection
      limits were below the micromolar range and the coefficient of correlation (R(2))
      was above 0.99 for most analytes. Working ranges were between 0.125-3.875 and 4.5
      139.5 microM. Sample pH had a major impact on the quantification of several
      metabolites, but measurements were robust within a pH range of 6.5-9.0.

PMID- 16798124
TI  - Neural stem cell separation from the embryonic avian olfactory epithelium by
      sedimentation field-flow fractionation.
AB  - The aim of the present study was to isolate neural stem cells from a complex
      tissue: the avian olfactory epithelium; by using sedimentation field flow
      fractionation (SdFFF). By using "Hyperlayer" elution mode, fraction collection
      and cell characterization methods, results shows that SdFFF could be a useful
      cell sorter to isolate an enriched, viable and sterile immature neural cell
      fraction from which the reconstitution of a complete epithelium was possible. In
      culture, SdFFF eluted cells first led to a "pseudoplacodal" epithelioid cell type
      from which derived "floating cells". These cells were then able to generate
      neurosphere-like structures which were composed of cell having many features of
      immature cells: undifferentiated, self-renewable and multipotentiality. Such a
      population might be used as a model to improve our understanding of the
      mechanisms of olfactory neoneurogenesis.

PMID- 16798125
TI  - Determination of NG,NG-dimethyl-L-arginine in rat plasma and dimethylarginine
      dimethylaminohydrolase activity in rat kidney using a monolithic silica column.
AB  - A fast, simple and sensitive column-switching high-performance liquid
      chromatography (HPLC)-fluorescence detection method was developed on a monolithic
      silica column for the determination of N(G),N(G)-dimethyl-L-arginine (ADMA),
      which is an endogenous nitric oxide synthase inhibitor. After fluorescence
      derivatization of plasma samples or homogenized tissues with 4-fluoro-7-nitro
      2,1,3-benzoxadiazole (NBD-F), the samples were injected into the HPLC system. The
      NBD-derivatized ADMA was trapped on a cation-exchange column and separated within
      15 min on a monolithic silica column. The detection limit for ADMA was 36 nM (250
      fmol per injection) when the signal-to-noise ratio was 3. A good linearity for
      calibration curve for ADMA was observed within the range of 140 nM (1.0 pmol per
      injection) - 140 microM (1.0 nmol per injection) using N(G)-monomethyl-L-arginine
      (L-NMMA) as an internal standard. The proposed method was used for the
      quantitative determination of ADMA in rat plasma. The concentrations of ADMA in
      rat plasma were 0.82+/-0.05 microM (n=4). Furthermore, the method developed was
      applied to determine dimethylarginine dimethylaminohydrolase (DDAH) enzyme
      activity in rat kidney, which was assayed by measuring the amount of ADMA
      metabolized by the enzyme.

PMID- 16798126
TI  - Infant mortality in Armenia, 1992-2003.
AB  - Health system reforms have been taken in Armenia during a time of dramatic
      economic and fiscal distress. It is important to assess trends in health
      indicators and ascertain if the changes in socio-economic systems affected the
      health status of infants as the most vulnerable part of the population. We find
      that infant mortality has fallen during the period c. 1992-2003 in spite of the
      difficult economic circumstances because of health-care procedures that were
      introduced. Particular attention is paid to the underreporting of infants' death
      cases in the state registration system as well as to estimating the role of
      different factors influencing infant mortality in Armenia.

PMID- 16798127
TI  - From Mawson's hut to skeletal growth: A life in science.

PMID- 16798128
TI  - Treatment of Paget's disease with hypercalcemia.

PMID- 16798129
TI  - Mucins and TFF peptides of the tear film and lacrimal apparatus.
AB  - The three-dimensional organization of the tear film, which is produced and
      drained by the different structures of the ocular adnexa, is essential for
      maintainance and protection of the ocular surface. This is facilitated by a class
      of large, highly glycosylated, hydrophilic glycoproteins, the mucins, which are
      usually expressed in association with a class of peptides having a well-defined,
      structurally conserved trefoil domain, the mammalian trefoil factor family (TFF)
      peptides. In this review, the latest information regarding mucin and TFF peptide
      function and regulation in the human lacrimal system, the tear film and the
      ocular surface is summarized with regard to mucous epithelia integrity,
      rheological and antimicrobial properties of the tear film and tear outflow, age
      related changes and certain disease states such as dry eye, dacryostenosis and
      dacryolith formation.

PMID- 16798130
TI  - Patients' perceptions of the side-effects of prostate cancer treatment--a
      qualitative interview study.
AB  - Primary prostate cancer treatment often results in suboptimal urinary, bowel
      and/or sexual function. These effects are not inevitable. After treatment
      patients typically report high health related quality of life (QoL) scores. This
      discrepancy between disease-specific and generic results raises the question
      which meaning side effects actually have to patients. In a qualitative study we
      explored two mechanisms which could possibly explain the discrepancy:
      insensitivity of generic QoL measures to these specific symptoms and adaptation
      to changed health (response shift). In semi-structured interviews with 33
      prostate cancer patients in the Netherlands we collected data on their opinions
      regarding health and QoL, we observed how respondents behaved when completing
      health status and QoL questionnaires, and solicited comments on a QoL
      questionnaire, its items, and its content validity. We observed that patients
      trivialized sexual (dys) function referring to old age. We found that while they
      might consider sexual, urinary, and bowel dysfunctions as problems, they did not
      take such dysfunctions into account when completing QoL measures because they did
      not view these dysfunctions as aspects of health. This finding reveals a so far
      unidentified cause of the insensitivity of generic measures of health status.
      Furthermore, response shift appeared to be present: many patients accepted the
      side effects as inevitable consequences of having been treated for prostate
      cancer, a condition they perceived as life threatening. We conclude that generic
      QoL measures cannot reveal the impact of sexual, urinary and bowel dysfunctions
      on patients because such dysfunctions are not perceived as health problems. By
      presenting these findings we want to draw attention to issues that complicate QoL
      assessments in general and in prostate cancer patients in particular.

PMID- 16798133
TI  - Shoulder magnetic resonance imaging.
AB  - MRI provides excellent soft tissue contrast and allows for multiplanar imaging in
      anatomic planes. Because of these advantages MRI has become the study of choice
      for imaging of shoulder pathology. Some structures, such as the rotator cuff,
      humeral head contour, and glenoid shape, are evaluated well with conventional
      MRI. When more sensitive evaluation of the labrum, capsule, articular cartilage,
      and glenohumeral ligaments is required or when a partial-thickness rotator cuff
      tear is suspected,magnetic resonance arthrography with intra-articular contrast
      can be performed. For MR arthrography contrast is injected directly into the
      glenohumeral joint. This article reviews the appearances of normal anatomic
      structures in MRI of the shoulder and disorders involving the rotator cuff and
      glenoid labrum.

PMID- 16798134
TI  - Sports-related injuries of the elbow: an approach to MRI interpretation.
AB  - MRI is a valuable tool for evaluating the athlete with elbow pain, particularly
      in those with nonlocalizable pain. MRI also is helpful in sorting out the cause
      of pain in athletes who may have acute trauma superimposed on tendinopathy or
      other chronic injuries from repetitive microtrauma. Even in athletes in whom the
      cause of pain confidently can be diagnosed clinically, MRI can document the
      injury severity, which can be helpful for estimating recovery time or in
      preoperative planning. By contributing to an accurate early diagnosis, MRI also
      can help minimize the time that athletes are away from their sports. The authors
      describe their approach to the MRI interpretation of elbow injuries in athletes,
      including osteochondral lesions, epicondylitis, and tears of the medial
      collateral ligament.

PMID- 16798136
TI  - Imaging of the painful shoulder in throwing athletes.
AB  - A wide spectrum of abnormalities can affect the throwing shoulder. The injuries
      are often particular to a specific phase of the throw and are well demonstrated
      with MR imaging. In this article, the authors review the phases of the throw, MR
      imaging techniques, and the MR appearances of the injuries associated with
      particular phases.

PMID- 16798135
TI  - Sports-related injuries of the wrist: an approach to MRI interpretation.
AB  - Sports-related injuries to the wrist range from minor sprains to severe soft
      tissue disruption that can pose a risk to the normal function of the upper
      extremity. It is important to identify the specific nature of such injuries so as
      to establish an accurate diagnosis and deliver appropriate treatment. MRI of the
      wrist has greatly benefited from the use of dedicated surface coils, which allow
      fine depiction of soft tissue and cartilaginous structures. A review of the
      normal anatomy, MR interpretation pitfalls, and most common abnormalities of the
      tendons, ligaments, triangular fibrocartilage complex, and nerves of the wrist
      are presented.

PMID- 16798137
TI  - MRI of the postoperative shoulder.
AB  - Pain in the postoperative shoulder is difficult for all individuals involved. The
      patient has already undergone a surgical procedure and is presenting now with
      pain possibly relating to a complication of the procedure or reinjury. In
      addition, the patient typically has undergone a series of maneuvers, from
      physical therapy to cortisone injection, without relief of the symptoms. For the
      orthopaedic surgeon the possibility of a complication of the procedure is
      disheartening. Finally, for the radiologist the postoperative shoulder usually is
      more difficult to interpret because of a change in the normal anatomy, not
      knowing exactly what was accomplished at surgery or what techniques or types of
      equipment were used, and, more typically, the presence of artifact.

PMID- 16798138
TI  - Entrapment neuropathies of the shoulder and elbow in the athlete.
AB  - MRI is a useful diagnostic method for evaluating nerve disease at the shoulder
      and elbow. MRI can depict the normal anatomy of the nerves, confirm and identify
      the cause of the neuropathy, identify the site of entrapment based on muscle
      denervation patterns, and detect unsuspected space-occupying lesions. MRI can
      also narrow down the differential diagnosis of nerve disease, such as in the case
      of suprascapular nerve syndrome versus Parsonage-Turner syndrome, or radial
      tunnel syndrome versus lateral epicondylitis. Large prospective studies with
      surgical correlation, however, are still necessary to better elucidate MRI's
      exact role in the assessment of entrapment neuropathies of the upper extremity.

PMID- 16798139
TI  - Imaging of upper extremity stress fractures in the athlete.
AB  - Although it is much less common than injuries in the lower extremities, an upper
      extremity stress injury can have a significant impact on an athlete. If an
      accurate and timely diagnosis is to be made, the clinician must have a high index
      of suspicion of a stress fracture in any athlete who is involved in a throwing,
      weightlifting, or upper extremity weight-bearing sport and presents with chronic
      pain in the upper extremity. Imaging should play an integral role in the work-up
      of these patients; if initial radiographs are unrevealing, further cross
      sectional imaging should be strongly considered. Although a three-phase bone scan
      is highly sensitive in this regard, MRI has become the study of choice at most
      centers.

PMID- 16798140
TI  - Imaging of ulnar-sided wrist pain.
AB  - Ulnar-sided wrist pain has long been a diagnostic problem, partly because of the
      complex anatomy and many possible causes of pain in this region. This article
      discusses anatomy, pathophysiology, and imaging appearance of the more common
      causes, including tears of the triangular fibrocartilage complex, disorders of
      the distal radioulnar joint, tears of the lunotriquetral ligament, disorders of
      the extensor carpi ulnaris tendon, disorders of the pisotriquetral joint, the
      impingement and impaction syndromes, and ulnar wrist masses. Along with clinical
      history and physical examination, imaging is important in evaluation of ulnar
      sided wrist pain. Conventional radiographs, conventional arthrography, CT, MRI,
      and MR arthrography are useful modalities that are often used in concert to help
      guide diagnosis and treatment.

PMID- 16798141
TI  - Injuries of the fingers and thumb in the athlete.
AB  - Injuries of the fingers and thumb in the athlete are common. Mallet finger,
      jersey finger, boutonniere deformity, Bennett and Rolando fractures, and
      gamekeeper's thumb are just a few of the injuries that can occur in athletes. A
      thorough understanding of the mechanism of injury, osseous and soft tissue
      abnormalities, imaging features, and treatment is important in the care of
      athletes. Prompt and accurate diagnosis is important and may help minimize
      outcomes of malunion, posttraumatic arthritis, and debility.

PMID- 16798142
TI  - Imaging of sports injuries of the upper extremity in children.
AB  - Competitive athletics in school-aged children has become the norm rather than the
      exception. The increased repetitive stresses placed on the upper extremity in a
      wide variety of sports result in a host of injuries unique to the skeletally
      immature athlete. This article focuses on a discussion of the more common upper
      extremity injuries encountered in the child athlete and the role of radiography
      and MRI in diagnosis and management.

PMID- 16798143
TI  - The role of ultrasound in the evaluation of sports medicine injuries of the upper
      extremity.
AB  - The two major imaging modalities used for assessment of soft tissue injuries are
      ultrasound and MRI. Although ultrasound of the extremities is used only to a
      limited extent in the United States, it is widely used in many other countries
      for evaluation of extremity injuries. This article first considers the advantages
      and disadvantages of MRI and ultrasound. Understanding these differences will
      help the reader understand the role of ultrasound as compared with MRI in
      evaluating upper extremity injuries. The uses of ultrasound for evaluating sports
      medicine injuries in specific regions of the upper extremity are then reviewed.
      Where the data are available, the reported accuracy of ultrasound is compared
      with MRI for each type of injury.

PMID- 16798144
TI  - Low field MRI: a review of the literature and our experience in upper extremity
      imaging.
AB  - Since its introduction to medical imaging in the early 1980s, MRI has become
      essential in diagnosis and treatment of musculoskeletal conditions. Most imaging
      in the United States is performed on high-field whole-body scanners (>1.0 T).
      Imaging on low (<0.5 T) and medium (0.5-1.0 T) field strengths using small, low
      cost, easily installed scanners in physicians' offices or imaging centers has
      gained popularity. These scanners can be useful in imaging the upper extremity
      from the shoulder to the fingers. This article provides an overview of the
      different extremity scanners available and their advantages and disadvantages, a
      brief review of the literature regarding their use, and a discussion of our
      experience in using the low-field extremity scanners in evaluating the upper
      extremity.

PMID- 16798145
TI  - How well do paramedics predict admission to the hospital? A prospective study.
AB  - A study was designed to determine whether paramedics accurately predict which
      patients will require admission to the hospital, and in those requiring
      admission, whether they will need a ward bed or intensive care unit (ICU)
      monitoring. This prospective, cross-sectional study of consecutive Emergency
      Medical Service (EMS) transport patients was conducted at an urban city hospital.
      Paramedics were asked to predict if the patient they were transporting would
      require admission to the hospital, and if so, whether that patient would be
      admitted to a ward bed or require an ICU bed. Predictions were compared to actual
      patient disposition. During the study period, 1349 patients were transported to
      our hospital. Questionnaires were submitted in 985 cases (73%) and complete data
      were available for 952 (97%) of these patients. Paramedics predicted 202 (22%)
      patients would be admitted to the hospital, of whom 124 (61%) would go the ward
      and 78 (39%) would require intensive care. The actual overall admission rate was
      21%, although the sensitivity of predicting any admission was 62% with a positive
      prediction value (PPV) of 59%. Further, the paramedics were able to predict
      admission to intensive care with a sensitivity of 68% and PPV of 50%. It is
      concluded that paramedics have very limited ability to predict whether
      transported patients require admission and the level of required care. In our EMS
      system, the prehospital diversion policies should not be based solely on
      paramedic determination.

PMID- 16798146
TI  - Impact of post-traumatic stress disorder and job-related stress on burnout: a
      study of fire service workers.
AB  - Burnout and stress are common, related problems in service professionals, and
      post-traumatic stress disorder (PTSD) is a major concern among fire service
      workers. The purpose of this study was to evaluate the impact of PTSD and job
      related stressors on burnout. A total of 243 fire service workers completed
      questionnaires, including the Impact of Event Scale-Revised (IES-R), Maslach
      Burnout Inventory (MBI), and Japan Brief Job Stress Questionnaire. Relationships
      were found between PTSD and burnout, and between job stressors and burnout.
      Social support reduced the impact on burnout. Stressors that impacted on burnout
      in fire service personnel were PTSD-related acute stress and general job-related
      chronic stress. Countermeasures, not only against job stress, but also against
      PTSD-related stress, are essential to prevent burnout. Social support and the
      development of human relationships in the work place are crucial in mitigating
      burnout.

PMID- 16798147
TI  - Carboxyhemoglobin measurement by hospitals: implications for the diagnosis of
      carbon monoxide poisoning.
AB  - Most case definitions for carbon monoxide (CO) poisoning include demonstration of
      an elevated blood carboxyhemoglobin (COHb) concentration. Further, it is
      generally believed that treatment of CO poisoning is more effective when
      performed as soon as possible after the exposure. This suggests that a hospital's
      inability to measure blood COHb could lead to delayed or missed diagnosis or
      treatment. This study evaluated the ability of hospitals in the Pacific Northwest
      to measure COHb levels. The clinical laboratory of every acute care hospital in
      Washington, Idaho, Montana, and Alaska was surveyed regarding the ability to
      measure COHb levels, the method utilized and the time required. If they could not
      measure COHb, they were asked whether samples are sent elsewhere, the location of
      the referral laboratory, and time required. Results were then compared to the
      list of hospitals referring CO-poisoned patients to a regional center for
      hyperbaric oxygen therapy from 2003-2004. In the four states, only 44% of acute
      care hospitals have the capability to measure COHb. The remaining 56% send blood
      samples to other laboratories. The average time to get a result is 10 +/- 10 min
      in hospitals with co-oximetry and 904 +/- 1360 min in those without, a difference
      of 15 h (p < 0.0001). When samples are sent out, the average distance is 121
      miles, often bypassing a hospital with CO-oximetry capability. Over 90% of CO
      poisoned patients referred for hyperbaric treatment came from hospitals able to
      measure COHb. Fewer than one-half of acute care hospitals in a four-state region
      have the capability to measure COHb levels. This has the potential to
      significantly impact diagnosis or treatment of patients with acute CO poisoning.

PMID- 16798148
TI  - Descriptive analysis of 258 emergency department visits by spina bifida patients.
AB  - To provide a descriptive analysis of emergency department (ED) patients with
      spina bifida, a retrospective chart review was conducted of ED patients with
      spina bifida. Data describing demographics, chief complaints, diagnostics,
      diagnoses, and disposition were collected. There were 125 patients with 258 ED
      visits. The most common presenting complaints included fever (n = 55), vomiting
      (36), headache (32), abdominal pain (23), and genitourinary symptoms (20). The
      most common diagnoses included urinary tract infection (n = 55), cellulitis (26),
      seizure (21), headache (17), dehydration (12), and shunt failure (11). Atypical
      presentations of conditions commonly associated with spina bifida occurred
      frequently. Forty-three percent of patients were admitted. In conclusion, spina
      bifida patients often present with serious illness requiring admission and with
      complications of their underlying condition. Therefore, atypical presentations of
      commonly associated conditions must be considered.

PMID- 16798149
TI  - Selective radiography in 100 patients with suspected shoulder dislocation.
AB  - We sought to prospectively validate an algorithm for selective radiography in the
      Emergency Department (ED) management of patients with suspected shoulder
      dislocation. Physicians ordered pre- and post-reduction radiographs based on an
      algorithm incorporating the mechanism of injury, previous dislocations, and the
      physician's clinical certainty of joint position. Follow-up consisted of
      telephone calls and chart review. Of 100 patients, 94 had shoulder dislocation,
      and 59% were recurrent. Thirty percent had both pre- and post-reduction
      radiographs, 45% had pre- or post-reduction only, and 25% had no shoulder films,
      yielding an overall 46% reduction in X-ray utilization. Mean ED times were
      significantly shorter for patients managed without radiographs. On telephone
      follow-up (76%) and chart review (100%), we found no missed fractures or
      persistent dislocations. Use of a clinical decision rule for selective
      radiography reduced the number of radiographs and time spent in the ED, while
      missing no fractures or dislocations.

PMID- 16798150
TI  - Subtle abdominal aortic injury after blunt chest trauma.
AB  - This case report describes a patient with an intimal flap of the abdominal aorta
      after a motor vehicle crash. The patient was an unrestrained driver with minimal
      anterior chest wall pain. This is a rare injury and one that is difficult to find
      due to its rarity. The lower cut of the chest CT scan found the injury. Its
      treatment with endovascular stenting is discussed.

PMID- 16798151
TI  - Air in the spinal canal associated with trauma.
AB  - Air in the spinal canal after trauma is uncommon. We report a case of a motor
      vehicle accident resulting in a thoracic fracture-dislocation. Air was discovered
      within the spinal canal on a computed tomography (CT) scan. This injury pattern
      proved to be a diagnostic dilemma because multiple etiologies existed.
      Pneumothorax, ruptured esophagus, facial sinus fractures, and herniated vertebral
      discs can result in this entity.

PMID- 16798152
TI  - An unusual cause of dyspnea.
AB  - Dyspnea is an alarming symptom for both the patient and the emergency physician.
      There are many causes of dyspnea, some of which are life-threatening, especially
      in the elderly patient. In addition to the usual cardiac and pulmonary causes
      such as congestive heart failure, asthma exacerbation, COPD, pneumonia, and
      pulmonary embolism, there are less common causes of dyspnea, which if not
      diagnosed and managed expeditiously may have dire consequences for both the
      patient and physician. We present a case of an elderly patient with a life
      threatening unusual cause of acute shortness of breath, a diaphragmatic hernia
      with sepsis.

PMID- 16798153
TI  - Creutzfeldt-Jakob disease: an emergency department presentation of a rare
      disease.
AB  - Creutzfeldt-Jakob Disease (CJD) is one of a group of neurodegenerative disorders
      causing spongiform encephalopathies. CJD is the most common human transmissible
      spongiform encephalopathy, or prion disease, but has an annual incidence of only
      0.4-1.8 cases per million population worldwide. The prognosis for this disease is
      very poor and there is currently no cure. Patients typically present with non
      specific neurological or psychiatric complaints and often have multiple physician
      visits before diagnosis, which requires histological examination of brain tissue.
      This patient had serial presentations to our Emergency Department, with
      progressive symptoms and multiple laboratory and radiological tests as well as
      consults, but her diagnosis remained unclear until her disease rapidly progressed
      and a brain biopsy was performed. With increasing concerns about prion diseases
      such as bovine spongiform encephalopathy (BSE)-or mad cow disease-and CJD,
      awareness of the symptoms and diagnostic challenges associated with these
      diseases will be helpful to emergency physicians.

PMID- 16798154
TI  - Spontaneous retropharyngeal hematoma: an unusual presentation of thoracic aortic
      dissection.
AB  - A 78-year-old woman presented to the Emergency Department with spontaneous
      ecchymosis and swelling of the neck. Ecchymosis was also evident on the posterior
      pharyngeal wall. A lateral soft tissue radiograph demonstrated a retropharyngeal
      hematoma, which was confirmed by computed tomography (CT). At this time there was
      no evidence of airway obstruction and she was admitted for observation. One week
      after admission she became acutely short of breath, and a chest radiograph at
      this time showed a large pleural effusion. Pleural drainage confirmed this to be
      a hemothorax. Subsequent CT revealed a thoracic aortic dissection with blood
      communicating into both the retropharyngeal space and the pleural cavity. The
      case highlights both an unusual presentation of thoracic aortic dissection, and
      also the potential for occult hemorrhage in cases of spontaneous retropharyngeal
      hematoma.

PMID- 16798155
TI  - Intracranial hemorrhage due to late hemorrhagic disease in two siblings.
AB  - Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease
      of the newborn (HDN); late HDN may be associated with serious and life
      threatening intracranial hemorrhage. Late HDN is characterized by intracranial
      bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency,
      occurring particularly in exclusively breastfed infants. Late HDN is still an
      important cause of mortality and morbidity in developing countries where vitamin
      K prophylaxis is not routinely practiced. In this study, we report on two
      siblings with intracranial bleeding who were fully breastfed without a routine
      supplementation of vitamin K. Vitamin K should be given to all newborns as a
      single, intramuscular dose of 1 mg.

PMID- 16798156
TI  - Are one or two dangerous? Phenothiazine exposure in toddlers.
AB  - Traditionally, pediatric phenothiazine exposures are considered dangerous even at
      low doses. The actual risk of exposure to 1-2 tablets is unclear. In an attempt
      to determine this risk, the authors performed a literature search, review of the
      American Association of Poison Control Center data, and evaluation of related
      resources (e.g., textbooks, bibliographies of relevant papers). This review
      reveals only sparse data from case reports regarding morbidity and mortality in
      the pediatric population despite years of clinical experience. Serious toxicity
      from exposure to low doses is rare and nearly always the result of chlorpromazine
      ingestion. Although the risk to the toddler ingesting 1-2 tablets seems to be
      extremely low, several factors should be considered when determining the need for
      triage to a health care facility.

PMID- 16798157
TI  - Paroxysmal atrial fibrillation precipitated by amiodarone-induced thyrotoxicosis
      five months after cessation of therapy.
AB  - Amiodarone is currently indicated for the treatment of life-threatening
      ventricular dysrhythmias. It is also used for the treatment of supraventricular
      dysrhythmias and as maintenance therapy after successful cardioversion of atrial
      flutter or atrial fibrillation. Adverse effects related to its expanded use are
      increasingly common. We describe a case of amiodarone-induced thyrotoxicosis
      occurring 5 months after cessation of therapy and discuss the pathophysiology and
      treatment of this disorder.

PMID- 16798158
TI  - Vasopressin treatment for cyclic antidepressant overdose.
AB  - Due to neurotransmitter reuptake inhibition, peripheral alpha receptor blocking
      effects, and sodium channel blockade, severe cyclic antidepressant poisoning may
      lead to intractable hypotension. We report a case of severe amitriptyline
      toxicity, with hypotension unresponsive to direct alpha receptor agonists after
      pH manipulation, but improved with intravenous vasopressin. Vasopressin use in
      the setting of cyclic antidepressant toxicity has not been previously reported.
      Vasopressin may be a beneficial agent in the treatment of recalcitrant
      hypotension associated with poisoning or overdose. The anecdotal nature of this
      report must be emphasized and the use of vasopressin requires further research to
      define efficacy, dose, and potential side effects.

PMID- 16798159
TI  - Upwardly concave ST segment morphology is common in acute left anterior
      descending coronary occlusion.
AB  - ST elevation (STE) in anterior precordial leads, in association with upwardly
      convex morphology (M) or straightM, is associated with anterior acute myocardial
      infarction (aAMI). Upwardly concaveM is characteristic of pseudoinfarction
      patterns such as early repolarization. A retrospective review was done of
      diagnostic electrocardiograms (EKG) of consecutive patients presenting to our
      Emergency Department (ED) who underwent emergent primary percutaneous
      intervention (PCI) and had proven left anterior descending (LAD) occlusion. If
      all leads from V2-V6 were upwardly concave, the EKG was classified as concaveM.
      If one lead was convex, the EKG had convexM. If no leads were convex and at least
      one was straight, it had straightM. Non-concaveM was defined as either convexM or
      straightM. Borderline STE was defined if the EKG did not have 2 consecutive leads
      with >or= 2 mm of STE. "Subtle," as opposed to "diagnostic," morphology was
      defined as concaveM without terminal QRS distortion. Data were analyzed with
      descriptive statistics. There were 37 patients identified who met the inclusion
      criteria and whose records were available for review. ConcaveM was found in 16 of
      37 (43%), 4 with terminal QRS distortion. Measurements resulted in a
      classification of borderline STE in 15 of 37 (41%) (9 of whom had subtle
      morphology) for Rater 1 and 12 of 37 (32%) (7 of whom had subtle morphology) for
      Rater 2, while 19% to 24% had both "subtle" morphology and borderline ST
      elevation. ConcaveM, as compared with convexM or terminal QRS distortion, was
      associated with a shorter duration of symptoms (p < 0.05). It is concluded that
      concave morphology cannot be used to exclude STEMI with LAD occlusion. Many
      patients with LAD occlusion have borderline ST elevation with subtle morphology.
      Concave morphology is associated with a shorter duration of symptoms.

PMID- 16798160
TI  - Comminuted femur fracture secondary to stress during the Boston marathon.
AB  - We report a case of a comminuted femur fracture secondary to repetitive stress in
      a healthy marathon runner. Stress fractures are common orthopedic injuries that
      result from normal muscular activity on deficient bone ("insufficiency
      fractures") or excessive, repetitive stresses on normal bone ("fatigue
      fractures"). Of recreational and professional sports, running accounts for a
      higher incidence of stress fractures, which have been reported to cause up to 15%
      of all injuries to runners. We report a case of a sub-trochanteric comminuted
      femoral stress fracture in a female marathon runner.

PMID- 16798161
TI  - Femoral phlebotomy: the vacuum tube method is preferable over needle syringe.
AB  - A syringe needle (SN) is commonly used to obtain blood specimens from the femoral
      vein. The vacuum tube (VT) method avoids the needle stick potential of the SN
      technique during transfer of blood from the syringe to the collection tubes. We
      compared the perceived safety, patient pain, and efficacy of SN and VT for
      femoral phlebotomy in a prospective trial. Of 64 patients entered, 38 (59%) had
      the VT technique and 26 (41%) had the SN technique. There was no significant
      difference in the success rate between VT and SN (100% vs. 95%, respectively).
      The VT method was somewhat faster than the SN method (104 +/- 109 vs. 181 +/- 149
      s, respectively, p = 0.06). Complications were infrequent and not different
      between the groups. The mean patient pain score +/- SD on a 10-cm visual analog
      scale for the VT and SN techniques were 2.6 +/- 2.2 and 3.7 +/- 2.7, respectively
      (p < 0.001). Physicians subjectively rated the safety of the procedure higher for
      the VT method than for the SN method. Medical personnel should consider use of
      the VT method instead of the traditional SN technique for femoral phlebotomy.

PMID- 16798162
TI  - Syncope with exertional dyspnea.

PMID- 16798163
TI  - Pneumothorax and parenchymal cavitation caused by airway injury after blunt
      trauma to the chest.

PMID- 16798165
TI  - Third pharyngeal pouch cyst and shortness of breath.

PMID- 16798164
TI  - An unusual right arm injury.

PMID- 16798166
TI  - Renal abscess.

PMID- 16798167
TI  - Diagnostic images of pulmonary Langerhans cell histiocytosis: an uncommon cause
      of secondary spontaneous pneumothorax.

PMID- 16798168
TI  - ST Segment elevation diagnostic algorithm.

PMID- 16798170
TI  - Cerebral venous thrombosis: hemorrhagic stroke requiring acute heparin
      anticoagulation.

PMID- 16798171
TI  - Isolated native non-rheumatic tricuspid valve endocarditis rarely is described in
      the absence of intravenous drug use, intracardiac catheters, or cardiac
      anomalies.

PMID- 16798172
TI  - Use of an adaptive aid to orotracheal intubation by a one-armed emergency
      physician.

PMID- 16798173
TI  - Effects of a fast-track area on emergency department performance.
AB  - To determine if a fast-track area (FTA) would improve Emergency Department (ED)
      performance, a historical cohort study was performed in the ED of a tertiary care
      adult hospital in the United States. Two 1-year consecutive periods, pre fast
      track area (FTA) opening-from February 1, 2001 to January 31, 2002 and after FTA
      opening-from February 1, 2002 to January 31, 2003 were studied. Daily values of
      the following variables were obtained from the ED patient tracking system: 1) To
      assess ED effectiveness: waiting time to be seen (WT), length of stay (LOS); 2)
      To assess ED care quality: rate of patients left without being seen (LWBS),
      mortality, and revisits; 3) To assess determinants of patient homogeneity between
      periods: daily census, age, acuity index, admission rate and emergent patient
      rate. For comparisons, the Wilcoxon test and the Student's t-test were used to
      analyze the data. Results showed that despite an increase in the daily census
      (difference [diff] 8.71, 95% confidence interval [CI] 6 to 11.41), FTA was
      associated with a decrease in WT (diff -51 min, 95% CI [-56 to -46]), LOS (diff 
      28 min, 95% CI [-31 to -23]) and LWBS (diff -4.06, 95% CI [-4.48 to -3.46]),
      without change in the rates of mortality or revisits. In conclusion, the opening
      of a FTA improved ED effectiveness, measured by decreased WT and LOS, without
      deterioration in the quality of care provided, measured by rates of mortality and
      revisits.

PMID- 16798174
TI  - Right diaphragm rupture with extended traumatic dissection of the descending
      aorta.
AB  - A 45-year-old man, with severe thoracic injury from a motor accident, is reported
      with traumatic aortic dissection type B and projection of the liver into the
      thoracic cavity due to a large rupture of the right hemidiaphragm. The patient
      was successfully managed with endoluminal stent placement in the descending
      thoracic aorta, and right thoracotomy for the repair of the diaphragmatic hernia.
      His postoperative course was uneventful. The co-existence of aortic traumatic
      dissection and right diaphragmatic rupture in trauma patients has never been
      reported in the literature previously, to our knowledge. Furthermore, the initial
      x-ray examination findings advocated injury of the right hemithorax and could be
      misleading. The diagnostic assessment must have a high index of suspicion,
      whereas the surgical manipulation needs to be fast and targeted to the major
      thoracic injuries of the patient.

PMID- 16798175
TI  - Minimally invasive pneumonectomy.
AB  - Technical advances have resulted in the growing popularity and success of video
      assisted thoracoscopic lobectomy for the treatment of nonsmall cell lung cancer.
      Several investigators have used similar techniques to safely perform
      pneumonectomies. Minimally invasive pneumonectomy may be indicated for patients
      who have centrally located malignant lesions and who are not candidates for
      sleeve resections. Adequate exposure of the proximal hilar vessels is mandatory.
      Short-term results are encouraging, but prospective long-term data are essential.

PMID- 16798176
TI  - Attracting outstanding students (premedical and medical) to a career in
      cardiothoracic surgery.

PMID- 16798177
TI  - No nodes is good nodes.

PMID- 16798178
TI  - Ethical process in human research published in thoracic surgery journals.
AB  - BACKGROUND: Media reports of ethical transgressions in research with human
      subjects have increasingly focused attention on clinical investigators and have
      served to undermine public confidence in medical research. A series of editorials
      in The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular
      Surgery in 2002 and 2003 emphasized integrity in research publication. We
      investigated the extent to which the ethical process was mentioned in reports of
      thoracic surgical research with human subjects since 2002. METHODS: We reviewed
      all reports of research involving human subjects published in these journals
      during the first 6 months of 2002, the first 6 months of 2003, and the last 6
      months of 2004 (n = 273, 291 and 288 for each time period, respectively with a
      total of 852). RESULTS: Ethical process was mentioned in 346 of 852 (41%)
      investigations. Comparing US and non-US studies, the rates of mentioning ethical
      process for prospective studies were 76 of 83 (92%) and 178 of 216 (82%),
      respectively, and for retrospective studies were 75 of 220 (34%) and 18 of 334
      (5%), respectively. Between 2002 and 2004, the rates of mentioning ethical
      process for prospective studies increased from 79 of 101 (78%) to 80 of 89 (90%),
      and for retrospective studies it increased from 17 of 172 (10%) to 59 of 199
      (30%). CONCLUSIONS: There was a significant increase in mention of ethical
      process from early 2002 to late 2004; however, documentation of appropriate
      ethical process in human research published in cardiothoracic journals remains
      less than ideal. The main burden of ensuring ethical process in human
      investigations rests with researchers, their institutions, and institutional
      review boards; however, editors can help rectify this problem by requiring
      adherence to national and international standards in the human subjects' research
      studies they publish. In adhering to ethical standards, investigators respect the
      research subjects' right of self-determination and foster public confidence in
      human research.

PMID- 16798179
TI  - Persistent effect of red cell transfusion on health-related quality of life after
      cardiac surgery.
AB  - BACKGROUND: Although red blood cell transfusion has been associated with an
      increase in early morbid outcomes and reduced long-term survival after cardiac
      surgery, its relationship to functional quality of life after surgery has not
      been previously explored. Our objective was to investigate the relationship
      between perioperative red blood cell and component transfusion and functional
      health-related quality of life 6 to 12 months after cardiac surgery. METHODS: Of
      12,536 patients undergoing cardiac surgical procedures between May 1995 and
      January 1999, 7,321 completed a self-administered Duke Activity Status Index
      (DASI) survey preoperatively and least one follow-up survey at nominally 6 or 12
      months postoperatively. The influence of baseline DASI, preoperative risk
      factors, clinical status, laboratory values, operative events, and postoperative
      morbidities on follow-up DASI were examined with ordinal regression modeling.
      RESULTS: After adjustment for preoperative DASI, demographic, cardiac and
      noncardiac comorbidity, type of surgery, postoperative complications, and
      interval between follow-up DASI, during which patients continued to improve (p <
      0.0001), postoperative functional status after cardiac surgery was incrementally
      worse the more perioperative red cells (p < 0.0001) and platelets (p = 0.02) that
      had been transfused. CONCLUSIONS: Red blood cell and platelet transfusion have an
      unintended persistently negative risk-adjusted effect on health-related quality
      of life after cardiac surgery that extends well beyond initial hospitalization.
      Reductions in functional recovery paralleled increasing units of red blood cells
      transfused.

PMID- 16798180
TI  - Clinical presentation, temporal relationship, and outcome in thirty-three
      patients with type 2 heparin-induced thrombocytopenia after cardiotomy.
AB  - BACKGROUND: Type 2 heparin-induced thrombocytopenia is an uncommon but often
      fatal complication of heparin, frequently difficult to diagnose after cardiac
      surgery. In this series, we record the clinical presentation, temporal
      relationship, and treatment outcome of patients diagnosed with heparin-induced
      thrombocytopenia postoperatively. METHODS: Thirty-three consecutive patients
      (1.1%) with a diagnosis of heparin-induced thrombocytopenia established by a
      greater than 50% drop in platelet count with or without a thrombotic event and a
      positive platelet factor-4 assay were reviewed. We recorded the clinical
      presentation, the time to presentation, treatment, and outcome (thrombosis,
      mortality). Univariate analysis was performed on 13 preoperative, operative, and
      postoperative variables. RESULTS: The cohort was at increased mortality risk as a
      result of age (69.4 years), reduced cardiac function (46.8%), nonbypass
      operations (57.6%), emergency surgery (21.2%), and implantation of three assist
      devices. The mean time to suspect heparin-induced thrombocytopenia
      postoperatively was 5.4 days, with 22 cases (66.6%) occurring within 5 days. All
      patients had previous (within 3 months) exposure to heparin, and 66.6% had
      ongoing treatment with heparin before surgery. Overall mortality was 33%;
      thrombotic complications occurred in 15 patients (45.5%), with a mortality of 7
      (46.6%) despite immediate cessation of heparin and treatment with a nonheparin
      analog. Thrombocytopenia without thrombosis occurred in 18 patients (54.5%), but
      a subgroup of 5 patients with nonthrombotic complications accounted for the 4
      (22.2%) deaths. CONCLUSIONS: Heparin-induced thrombocytopenia after cardiac
      surgery is uncommon but may occur within 5 days of surgery, further complicating
      diagnosis and treatment. Thrombotic complications result in a high mortality
      despite treatment with a nonheparin analog, and a subgroup of patients with
      thrombocytopenia fared poorly.

PMID- 16798181
TI  - Invited commentary.

PMID- 16798182
TI  - Outcome evaluation of the bridge-to-bridge concept in patients with cardiogenic
      shock.
AB  - BACKGROUND: Patients with cardiogenic shock can be stabilized by percutaneous
      implantation of extracorporeal membrane oxygenation (ECMO). If weaning from ECMO
      is impossible, the implantation of a ventricular assist device (VAD) is required.
      Patients either go for recovery of myocardial function (bridge to recovery) or
      for heart transplantation (bridge to transplant). METHODS: One hundred thirty-one
      patients were supported with ECMO between March 1995 and November 2005. Reasons
      for ECMO implantation were acute heart failure, acute or chronic heart failure,
      and postcardiotomy heart failure. In 28 patients, subsequent VAD implantation was
      necessary (bridge to bridge concept). RESULTS: Fourteen bridge to bridge patients
      (50%) became long-time survivors with a mean follow-up of 39 months. Risk factors
      for mortality were status post-cardiopulmonary resuscitation and elevated lactate
      and bilirubin levels before VAD implantation. Complications after ECMO and VAD
      implantation were bleeding and thromboembolic events. The most common cause of
      death was multiorgan failure. CONCLUSIONS: Bridge to bridge is a successful
      concept for selected patients with cardiogenic shock. During ECMO support,
      patients can be evaluated for comorbidities. For patients with a combination of
      risk factors (status post-cardiopulmonary resuscitation, elevated lactate levels,
      and impaired liver function), VAD implantation should be considered very
      carefully.

PMID- 16798183
TI  - Invited commentary.

PMID- 16798184
TI  - Intraaortic balloon pumping during cardioplegic arrest preserves lung function in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Linear flow during cardiopulmonary bypass is considered a potential
      mechanism of lung damage in patients with chronic obstructive pulmonary disease
      (COPD). We evaluated differences in lung function of patients with COPD
      undergoing preoperative intraaortic balloon pumping (IABP), between linear flow
      during cardiopulmonary bypass (IABP-off) and maintenance of pulsatile flow (IABP
      on at automatic 80 bpm) during cardioplegic arrest. METHODS: Fifty patients with
      COPD undergoing preoperative IABP were randomized between January 2004 and July
      2005 to receive nonpulsatile cardiopulmonary bypass with IABP discontinued during
      cardioplegic arrest (25 patients; group A), or IABP-induced pulsatile
      cardiopulmonary bypass (25 patients; group B). Hospital outcome, need for
      noninvasive ventilation, oxygenation (partial pressure of oxygen, arterial to
      fraction of inspired oxygen [Pao(2)/Fio(2])), respiratory system compliance, and
      scoring of chest radiographs were compared. RESULTS: There were no hospital
      deaths, no IABP-related complications, and no differences in postoperative
      noninvasive ventilation (group A: 6 of 25, 24.0% vs group B: 5 of 25, 20%; p =
      not significant [NS]). One patient in both groups developed pneumonia (p = NS).
      Intensive care and hospital stay were comparable (p = NS). Group B showed lower
      intubation time (8.3 +/- 5.1 hours versus group A: 13.2 +/- 6.0; p = 0.001),
      better Pao(2)/Fio(2) at aortic declamping (369.5 +/- 93.7 mm Hg vs 225.7 +/-
      99.3; p = 0.001) at admission in intensive care (321.3 +/- 96.9 vs 246.2 +/-
      109.7; p = 0.003), and at 24 hours (349.8 +/- 100.4 vs 240.8 +/- 77.3; p =
      0.003). The respiratory system compliance was better in group B at the end of
      surgery (56.4 +/- 8.2 mL/cm H(2)O vs 49.4 +/- 7.0; p = 0.004) and 8 hours
      postoperatively (76.4 +/- 8.2 vs 59.4 +/- 7.0; p = 0.0001), as well as scoring of
      chest radiograph at intensive care admission (0.20 +/- 0.41 vs 0.38 +/- 0.56; p =
      0.05) and on the first day (0.26 +/- 0.45 vs 0.50 +/- 0.67; p = 0.025).
      CONCLUSIONS: Automatic 80 bpm IABP during cardioplegic arrest preserves lung
      function in patients with COPD.

PMID- 16798185
TI  - Noninvasive midterm follow-up of radial artery bypass grafts with 16-slice
      computed tomography.
AB  - BACKGROUND: The standard invasive procedure to evaluate graft patency is
      selective coronary angiography. The recent introduction of a new generation of
      multidetector row computed tomography made possible the noninvasive study of
      grafts with excellent results in terms of visualization and resolution. We used
      computed tomography to study all patients with a radial artery graft operated on
      in 2002. METHODS: Between April and October 2005, we reviewed all patients
      operated on by coronary artery bypass grafting at our institution between January
      and December 2002. A total of 62 patients received a radial artery graft. Of
      these, 22 were lost at the time of follow-up. The other 40 patients were enrolled
      for a multidetector row computed tomography study. Demographic and instrumental
      data were collected for all the patients. A total number of 145 grafts were
      studied, with complete and excellent visualization. RESULTS: The scans revealed a
      97.77% (44 of 45) patency rate for left internal mammary arteries, 90.57% (48 of
      53) for vein grafts, and 73.91% (34 of 46) for radial arteries (mammary artery
      plus vein grafts versus radial artery patency, p < 0.001). If analyzed for target
      vessel, we found the poorest result of radial grafts when placed on the right
      coronary artery (40% [2 of 5] patency rate). CONCLUSIONS: Noninvasive control of
      previously bypassed patients is feasible, with no discomfort for them and
      excellent visualization of grafts. The use of the radial artery as a conduit for
      bypass graft can be achieved with good results, after a careful choice of the
      target vessel.

PMID- 16798186
TI  - Randomized controlled trial of pericardial blood processing with a cell-saving
      device on neurologic markers in elderly patients undergoing coronary artery
      bypass graft surgery.
AB  - BACKGROUND: Processing of pericardial shed blood with a cell-saving device was
      claimed to prevent lipid microembolization and to protect from neurocognitive
      dysfunction after cardiopulmonary bypass. The present study tested the hypothesis
      that processing of pericardial shed blood with a cell-saving device during
      cardiopulmonary bypass would significantly decrease serum levels of protein
      S100B, and improve brain oxygen saturation and neurologic outcome, all markers of
      brain injury in elderly patients. METHODS: Forty patients, 65 years of age and
      older, undergoing coronary artery bypass graft with cardiopulmonary bypass, were
      prospectively randomly assigned to processing of pericardial shed blood with a
      cell-saving device or to conventional use of a standard closed venous reservoir
      where cardiotomy blood was collected and reinfused through the arterial circuit
      (control group). Serum in S100B was measured 30 minutes, 4 hours, 24 hours, and
      48 hours after surgery. Near-infrared spectroscopy monitoring was performed
      during the procedure and the National Institutes of Health stroke scale was
      measured before surgery and at the time of discharge of the hospital. RESULTS:
      Patients in the cell-saving device group averaged 72 +/- 3 years of age and
      underwent 3.1 +/- 0.7 coronary artery grafts with a mean of 62 +/- 20 minutes of
      cardiopulmonary bypass time. Patients in the control group averaged 75 +/- 4
      years of age (p = 0.03) and underwent 3.3 +/- 0.6 coronary artery grafts (p =
      0.49) with a mean of 75 +/- 25 minutes of cardiopulmonary bypass time (p = 0.12).
      The quantity of blood administered from the cell-saving device averaged 281 +/-
      162 mL per patient. Serum protein S100B levels averaged 0.06 +/- 0.03 before
      surgery and 0.51 +/- 0.23 microg/L 30 minutes after surgery in the cell-saving
      device patients compared with 0.076 +/- 0.04 before surgery (p = 0.32) and 1.48
      +/- 0.66 (p < 0.0001) in the control patients. The near-infrared spectroscopy
      baseline mean value of left and right cortical region was 58% +/- 12% and 55% +/-
      7% in the cell-saving device group versus 59% +/- 7% and 53% +/- 6% in the
      control group (p = 0.67 and 0.36), and no difference occurred over time in each
      group. The National Institutes of Health stroke score before and after surgery
      was similar in the two groups. There was one cerebrovascular complication in the
      control group (1 of 20, 5%) after surgery. CONCLUSIONS: The difference between
      the two groups occurred 30 minutes after surgery, at which time serum levels of
      protein S100B were significantly higher in the control group compared with cell
      saving device patients. Although use of the cell-saving device was not associated
      with higher brain oxygen saturation nor changes in the National Institutes of
      Health stroke score, it is associated with lesser release of nonspecific markers
      of brain injury in elderly patients.

PMID- 16798187
TI  - Invited commentary.

PMID- 16798188
TI  - EuroSCORE predicts immediate and late outcome after coronary artery bypass
      surgery.
AB  - BACKGROUND: The European system for cardiac operative risk evaluation score
      (EuroSCORE) has been shown to be of value in identifying patients at high risk
      for adverse immediate postoperative outcome after adult cardiac surgery. The aim
      of the present study was to evaluate EuroSCORE in predicting the 12-year outcome
      of patients who underwent on-pump coronary artery bypass surgery (CABG). METHODS:
      We calculated the EuroSCORE in 917 patients who underwent CABG. The median follow
      up was 11.7 years. RESULTS: Both additive and logistic EuroSCORE had an area
      under the receiver operating characteristic curve of 0.856 for prediction of 30
      day postoperative death. Among 912 operative survivors, the 10-year survival
      rates according to quintiles of additive EuroSCORE were 87.9%, 83.9%, 85.2%,
      76.0%, and 51.3% (p < 0.0001). The 10-year survival rates according to quintiles
      of logistic EuroSCORE were 87.9%, 85.4%, 86.5%, 76.9%, and 58.9% (p < 0.0001).
      CONCLUSIONS: EuroSCORE is a relevant predictor of immediate and late outcome
      after on-pump CABG.

PMID- 16798189
TI  - Superior mesenteric artery blood flow modifications during off-pump coronary
      surgery.
AB  - BACKGROUND: Patients undergoing cardiac surgery are at increased risk of gut
      hypoperfusion. During off-pump surgery, hemodynamic derangements at the time of
      heart displacement could reduce splanchnic perfusion, outweighing the beneficial
      effects of avoiding cardiopulmonary bypass. The purpose of this study is to
      assess, prospectively, blood flow modifications in the superior mesenteric artery
      during off-pump surgery using transesophageal echocardiography. METHODS: In 19
      patients undergoing multivessel elective off-pump coronary revascularization,
      systemic hemodynamics and superior mesenteric flow were assessed. Blood flow in
      the superior mesenteric artery was evaluated with duplex ultrasound using a
      transesophageal echo probe. Measurements were made four times: T0 (baseline), T1
      (left anterior descendent anastomosis), T2 (heart displacement to expose the
      inferolateral and inferior walls), and T3 (closed chest, at the end of surgery).
      RESULTS: Superior mesenteric blood flow significantly decreased at T2 (from 426.4
      +/- 83.1 mL to 212.9 +/- 48.6 mL, p < 0.001), when also cardiac output was
      reduced. The percentage of the cardiac output directed toward the mesenteric
      arterial bed was also decreased at this time. At the end of surgery (T3), whereas
      cardiac output returned to the initial values, mesenteric flow was significantly
      increased compared with baseline, with a higher percentage of the systemic output
      flowing through the superior mesenteric artery. CONCLUSIONS: Hemodynamic changes
      during off-pump coronary surgery induce a significant mesenteric hypoperfusion
      followed by a hyperemic response at the end of surgery. Transesophageal echo
      Doppler allows the intraoperative measurement of blood flow distribution to
      splanchnic viscera.

PMID- 16798190
TI  - Invited commentary.

PMID- 16798191
TI  - Coronary artery bypass grafting using an abdominal artery as an inflow.
AB  - BACKGROUND: In multiple bypass surgery, when the ascending aorta cannot be used
      as an inflow, it is sometimes necessary to use an abdominal artery. This
      technique is useful when a re-median sternotomy might damage a patent graft in
      patients undergoing reoperations or when the gastroepiploic artery is unsuitable
      for use as a graft. METHODS: The subjects were 17 patients in whom an abdominal
      artery was used as an inflow. In these 17 patients, 9 underwent surgery for the
      first operation, while 8 underwent surgery for the reoperation. As an inflow, the
      gastroduodenal artery was used in 8 patients, the common hepatic artery in 4
      patients, the left gastric artery in 3 patients, the right gastric artery in 1
      patient, and the middle colic artery in 1 patient. The target coronary artery was
      the right posterior descending artery in 13 patients, the atrioventricular artery
      in 2 patients, and the circumflex artery in 4 patients. Sequential bypass was
      performed on 2 patients. RESULTS: None of the patients died during surgery.
      Symptoms disappeared postoperatively in all patients; postoperative angiography
      showed that all grafts were patent. CONCLUSIONS: The present technique is useful
      when the ascending aorta cannot be used as an inflow or when a bypass to a region
      with a large perfusion area is needed in multiple bypass surgery.

PMID- 16798192
TI  - Invited commentary.

PMID- 16798193
TI  - Incomplete circle of Willis and right axillary artery perfusion.
AB  - BACKGROUND: The aim of our anatomic study was to assess whether the commonly used
      method of perfusion through the right axillary artery is sufficient in providing
      uniform distribution of blood to both hemispheres of the brain in patients
      undergoing surgery of the aortic arch. We considered that critical arteries to
      examine are anterior and left posterior communicating arteries of the circle of
      Willis because the absence or insufficiency of either one would drastically
      endanger perfusion to the left hemisphere of the brain. The existence and the
      diameters of these arteries were studied. METHODS: The material was collected as
      a part of normal forensic medicine autopsies. The anatomy of the cerebral
      arteries of 87 deceased individuals was assessed by angiography and permanent
      silicone casts. A new classification was created for this study. According to a
      recent observation in the literature we defined the minimum threshold of arterial
      diameter that allows cross flow to be 0.5 mm. We also repeated analyses using 1
      mm as a threshold, which has also been recommended. RESULTS: In our material 22%
      of the anterior communicating arteries and 46% of the left posterior
      communicating arteries were missing. In this anatomic population the perfusion to
      the left hemisphere might have been insufficient in 14% of the patients at a
      threshold of 0.5 mm and in 17% at a threshold of 1 mm. CONCLUSIONS: When the
      right axillary artery is used for perfusion, the circulation to the contralateral
      hemisphere seems to be good for most patients undergoing operations of the aortic
      arch, but additional means of brain protection are still needed.

PMID- 16798194
TI  - Invited commentary.

PMID- 16798195
TI  - Thoracic aorta false aneurysm: what surgical strategy should be recommended?
AB  - BACKGROUND: Thoracic aorta false aneurysms (TAFA) are a surgical challenge. The
      best technical approach remains uncertain. METHODS: Between 1981 and 2004, 57
      patients underwent operation for TAFA (mean age 57 +/- 18 years; 43 [75%] were
      male). Symptoms included dyspnea 25 (44%), chest pain 22 (39%), and fever 18
      (32%). Twelve (21%) were asymptomatic. Thirty-seven (65%) had undergone previous
      operation with a mean interval between operations of 80 +/- 90 months. Fifteen
      (26%) had a mycotic etiology. The TAFA involved the aortic root in 10 (18%),
      ascending aorta in 28 (49%), arch in 6 (11%), and descending aorta in 13 (32%).
      Twenty-one (37%) required femorofemoral cannulation and 28 (49%), circulatory
      arrest. Surgical techniques included graft replacement in 27 (47%), composite
      root in 10 (18%), patch repair in 10 (18%), and direct suture in 10 (18%).
      RESULTS: Operative mortality was 7% (4 patients). Four of 32 (13%) had massive
      hemorrhage during redo sternotomy, and all of these had planned extramediastinal
      cannulation (all survived). Follow-up was 100% for 349 patient-years. Actuarial
      survival was 77% +/- 6%, 63% +/- 8%, and freedom from recurrent TAFA was 87% +/-
      5% and 83% +/- 7%, at 5 and 10 years, respectively. Univariate analysis
      identified TAFA greater than 55 mm, urgent operation, and NewYork Heart
      Association functional class III or IV as predictors of hemorrhage during redo
      sternotomy. Obesity and ejection fraction of 35% or less were predictors of
      operative death. CONCLUSIONS: Thoracic aorta false aneurysm symptoms may be
      minimal, and consequently a high degree of suspicion plus serial imaging is
      warranted. Extramediastinal cannulation, deep hypothermia, and circulatory arrest
      are required for large mediastinal TAFA. Despite serious risks, TAFA correction
      is possible with good long-term results.

PMID- 16798196
TI  - Resection of the descending thoracic aorta: outcomes after use of hypothermic
      circulatory arrest.
AB  - BACKGROUND: Use of hypothermic circulatory arrest (HCA) for operations on the
      descending thoracic aorta is controversial. While deep hypothermia may provide
      better end-organ and spinal cord function, prolonged cardiopulmonary bypass and
      circulatory arrest may increase morbidity. This study assessed outcomes after use
      of HCA for descending thoracic aortic resection in a large cohort of consecutive
      patients. METHODS: Hypothermic circulatory arrest was utilized if arch or
      extensive descending thoracic aortic resection was required, or if aortic
      pathology precluded cross-clamping. One hundred thirty-two patients (mean age,
      61.3 years) were identified. Diagnosis included fusiform (41.2%) or saccular
      aneurysm (10.7%) and acute (4.6%) or chronic (38.9%) dissection. Twenty-one
      patients presented with rupture. Arch resection (distal arch 100, total arch 11)
      was required in 111 patients (84.1%). The extent of descending thoracic aortic
      resection (required in 94%) included proximal third in 41 patients, proximal two
      thirds in 6, and complete thoracic aorta in 77. The proximal anastomosis was
      performed with total body HCA while the distal anastomosis was constructed with
      lower body HCA only (duration upper body HCA 33.7 +/- 8.0 minutes; total duration
      lower body HCA 71.3 +/- 24.2 minutes). RESULTS: Thirty-day mortality was 6.0%.
      Neurologic events included stroke (6.8%) and permanent lower extremity paralysis
      paresis (4.5%). Temporary dialysis was needed in 7 (5.3%), though only 2 patients
      required permanent dialysis (1.9%). Independent predictors of a composite
      endpoint of death, stroke, permanent paralysis, or dialysis included duration of
      lower body HCA (p = 0.03) and major postoperative infection (p = 0.003).
      CONCLUSIONS: Adjunctive use of deep hypothermic circulatory arrest for descending
      thoracic aortic resection affords excellent preservation of end-organ and spinal
      cord function with acceptable rates of mortality and significant morbidity.

PMID- 16798197
TI  - C-reactive protein levels and atrial fibrillation after cardiac surgery in women.
AB  - BACKGROUND: The aim of this study was to evaluate whether risk for postoperative
      atrial fibrillation in women is related to preexisting inflammation as detected
      by plasma C-reactive protein (CRP) concentrations. We further sought to assess
      the importance of atrial fibrillation for outcome after cardiac surgery in women.
      METHODS: The CRP was measured before coronary artery bypass grafting and (or)
      valvular surgery using cardiopulmonary bypass in 141 women. Univariate and
      multivariate analyses were used to evaluate for differences in CRP levels between
      women with and without atrial fibrillation, and to assess for the importance of
      the arrhythmia and postoperative outcomes. RESULTS: Atrial fibrillation developed
      in 46 (33%) women. Neither CRP concentrations (median +/- standard error, 13.3 +/
      2.5 mg/L vs 11.7 +/- 1.4 mg/L, p = 0.847), nor the frequency of elevated levels
      (defined as > upper 95% confidence interval or >19.2 mg/L) (19% vs 21%, p =
      0.807) differed between women with or without atrial fibrillation. Patient age
      and previous stroke, but not CRP levels, were independently associated with
      atrial fibrillation. Women with atrial fibrillation were more likely to have low
      cardiac output syndrome (p = 0.018), stroke (p = 0.031), longer duration of
      hospitalization in the intensive care unit (p = 0.012) and on the postoperative
      (p = 0.0008) ward, and they were more likely to require an extended care facility
      after surgery (p = 0.046). CONCLUSIONS: In contrast to findings from studies that
      have included mostly men, preoperative CRP concentrations are not associated with
      risk for atrial fibrillation after cardiac surgery for women. Postoperative
      atrial fibrillation in women is associated with increased risk for stroke, longer
      hospitalization, and extended care facility admission.

PMID- 16798199
TI  - Invited commentary.

PMID- 16798198
TI  - Is interferon gamma suppression after cardiac surgery caused by a decreased
      interleukin-12 synthesis?
AB  - BACKGROUND: The suppression of interferon gamma (IFN-gamma) synthesis after
      cardiac surgery is discussed as a cause of postoperative immunosuppression that
      predisposes to postoperative infectious complications. Because several studies
      have suggested that interleukin-12 (IL-12) production by monocytes and
      macrophages is reduced after cardiac surgery, this might cause a decrease in IFN
      gamma release. To better understand these processes, we assessed the role of IL
      12 in IFN-gamma synthesis in vitro before and after cardiac surgery. METHODS:
      Heparinized whole blood samples were obtained from 20 patients undergoing
      elective cardiac surgery preoperatively (day 0) and on the first (day 1), third
      (day 3), and fifth (day 5) postoperative days, and stimulated (24 hours) with
      staphylococcal enterotoxin B and lipopolysaccharide. Recombinant IL-12 was added
      at each time point investigated. Interferon-gamma, IL-12, IL-2, IL-4, and IL-5
      concentrations and histocompatibility leukocyte antigen-DR (HLA-DR) expression on
      monocytes and macrophages were assayed by flow cytometry. RESULTS: The HLA-DR
      expression, IL-12 release, and IFN-gamma synthesis were significantly reduced on
      day 1, day 3, and day 5. Recovery began on day 3. Interleukin-12 caused a
      significant increase in IFN-gamma synthesis at each time point. When IL-12 was
      added, IFN-gamma synthesis returned to preoperative levels on days 3 and 5.
      CONCLUSIONS: The synthesis of IFN-gamma is significantly reduced after cardiac
      surgery. The application of IL-12 causes an increase in IFN-gamma synthesis
      before surgery and a return of IFN-gamma to preoperative levels within a few days
      after surgery. These findings suggest that postoperative suppression of IFN-gamma
      release is caused by a decrease in IL-12 synthesis. In addition, IL-12 has a
      mainly proinflammatory effect both before and after surgery.

PMID- 16798200
TI  - Transapical aortic valve implantation: an animal feasibility study.
AB  - BACKGROUND: Percutaneous aortic valve implantation has recently been performed in
      nonsurgical patients with severe aortic stenosis. Retrograde valve delivery has
      been problematic because of the size of the delivery system and concomitant
      peripheral vascular disease. We investigated a minimally invasive approach
      through the left ventricular apex for antegrade placement of a device-deliverable
      valve. METHODS: Transapical aortic valve implantation was performed using a 23-mm
      equine valve mounted on a stainless steel stent in 24 swine (weight range, 35 to
      45 kg). A limited or full sternotomy approach was used to access the apex of the
      heart. The crimped valve was introduced through a sheath in the left ventricular
      apex. Fluoroscopy and echocardiography were used for guidance. Deployments were
      performed on the beating heart either with ventricular unloading using femoral
      extracorporeal circulation or rapid ventricular pacing. RESULTS: All valves were
      successfully delivered at the selected target site with acceptable visualization
      of the noncalcified aortic annulus. Valve migration occurred during eight
      deployments (two distal and six retrograde) secondary to persistent cardiac
      output, unfavorable annular anatomy, and dislodgement by the delivery catheter.
      Exact positioning of the nonmigrated valves at the aortic annulus was examined by
      necropsy of all animals at the end of the procedures. Paravalvular leak was noted
      in 14 of 18 (77.8%) valves remaining in situ. CONCLUSIONS: The transapical
      approach was used for the successful antegrade placement of a stented valve,
      obviating the technical problems associated with a large delivery system
      transiting the peripheral vascular system. Stent design contributing to
      paravalvular leak remains problematic.

PMID- 16798201
TI  - Age- and gender-related differences in ischemia/reperfusion injury and
      cardioprotection: effects of diazoxide.
AB  - BACKGROUND: Recent studies have demonstrated that aging is associated with
      reduced tolerance to ischemia and that the aged (not senescent) female heart has
      greater susceptibility to ischemia as compared with the aged male heart.
      Previously, we have shown that ischemia can be modulated with cardioplegia in the
      male heart; however, efficacy in the female heart was unknown. METHODS: In this
      study, male and female mature (15 to 20 weeks) aged (>32 months) rabbit hearts (n
      = 134) were subjected to Langendorff perfusion. Control hearts were perfused for
      180 minutes. Global ischemia hearts received 30 minutes of equilibrium, 30
      minutes of global ischemia, and 120 minutes of reperfusion. Cardioplegia +/-
      diazoxide was infused separately, 5 minutes before global ischemia. RESULTS:
      Global ischemia significantly decreased postischemic functional recovery and
      significantly increased infarct size in the mature and aged male and female heart
      (p < 0.05 versus control). The effects of global ischemia were significantly
      exacerbated (p < 0.05) in the aged heart as compared with the mature heart.
      Cardioplegia +/- diazoxide significantly increased postischemic functional
      recovery and significantly decreased infarct size in mature male and female
      hearts, but these effects were significantly decreased in the aged heart (p <
      0.05) and in the aged female as compared with the aged male heart. CONCLUSIONS:
      Postischemic functional recovery and infarct size are affected by age but not by
      gender. The cardioprotection afforded by cardioplegia is affected by age and
      gender with a strong age-by-gender interaction for end-diastolic pressure and
      infarct size. Our results indicate that currently optimized cardioplegia
      protocols effective in the male heart are not as efficacious in the aged female
      heart.

PMID- 16798202
TI  - Total liquid ventilation reduces lung injury in piglets after cardiopulmonary
      bypass.
AB  - BACKGROUND: Cardiopulmonary bypass may cause lung injury that does not respond to
      traditional therapies. Total liquid ventilation has been developed as an
      alternative ventilatory strategy for severe lung injury. The aim of this study is
      to investigate the effect of total liquid ventilation on lung injury in piglets
      after cardiopulmonary bypass. METHODS: After exposure to 60 minutes of cardiac
      arrest and weaning from cardiopulmonary bypass, 12 piglets (4.2 +/- 0.3 kg) were
      randomly treated with conventional gas ventilation (control group) or total
      liquid ventilation (study group) for 240 minutes. Samples for blood gas analysis
      were collected before, and at 30-minute intervals after, cardiopulmonary bypass.
      The degree of lung injury was quantified by histologic examination. The
      inflammatory cells and the levels of interleukin-6, interleukin-8, and
      myeloperoxidase in bronchoalveolar lavage were analyzed. RESULTS: Neutrophil and
      macrophage count in bronchoalveolar lavage were significantly decreased in the
      study group (52.4 +/- 6.82 vs 0.46 +/- 0.11 10(4)/mL; 58.33 +/- 0.88 vs 4.37 +/-
      0.90 10(5)/mL; p < 0.001, respectively). The inflammation score and the total
      lung injury score were also reduced in the study group (4.39 +/- 1.14 vs 2.61 +/-
      1.09; 11.06 +/- 1.66 vs 6.94 +/- 1.43; p < 0.05, respectively). The
      concentrations of interleukin-6 and myeloperoxidase in bronchoalveolar lavage
      were significantly reduced in the study group (81.32 +/- 15.23 vs 53.55 +/- 15.48
      pg/mL, 75.00 +/- 9.19 vs 50.00 +/- 7.37 u/mL; p < 0.05, respectively), whereas
      the interleukin-8 levels were similar between both groups (551.63 +/- 119.34 vs
      563.68 +/- 137.14 pg/mL, p > 0.05). CONCLUSIONS: Total liquid ventilation with FC
      77 (3M, St. Paul, MN) reduces biochemical and histologic lung injury in piglets
      after cardiopulmonary bypass.

PMID- 16798203
TI  - Better protection of pulmonary surfactant integrity with deep hypothermia and
      circulatory arrest.
AB  - BACKGROUND: The influence of deep hypothermia with either circulatory arrest
      (DHCA) or low-flow (DHLF) perfusion on pulmonary surfactant metabolism in
      neonates undergoing cardiac surgery remains unknown. This study was conducted to
      determine the influence of either strategy on surfactant metabolism and pulmonary
      function with neonatal piglet model. METHODS: Sixteen piglets underwent 90-minute
      deep hypothermia, either with circulatory arrest or low-flow perfusion (30 mL.kg(
      1).min(-1)) at 18 degrees C. Disaturated phosphatidylcholine, total
      phospholipids, and total proteins from tracheal aspirates were measured serially
      until the end of cardiopulmonary bypass. Lung static compliance, airway
      resistance, and arterial blood oxygen partial pressure to inspired oxygen
      fraction were also measured. RESULTS: The DHLF caused more significant decrement
      of pulmonary static compliance than DHCA (3 +/- 0.4 mL.cmH2O(-1) vs 3.5 +/- 0.3
      mL.cmH2O(-1) at 90 minutes of deep hypothermia). Arterial blood oxygen partial
      pressure to inspired oxygen fraction decreased more significantly after
      cardiopulmonary bypass in the DHLF group than the DHCA group (205 +/- 84 mm Hg vs
      302 +/- 96 mm Hg). The DHLF caused more severe decrement of disaturated
      phosphatidylcholine total phospholipids (50% +/- 21% vs 67% +/- 23% of baseline
      at 90 minutes of deep hypothermia) and disaturated phosphatidylcholine total
      proteins (58% +/- 23% vs 73% +/- 23% of baseline at 90 minutes of deep
      hypothermia) than DHCA. More significant water retention developed in the lung in
      the DHLF group than in the DHCA group. The extent of surfactant depletion was
      statistically correlated with the extent of pulmonary functional deterioration in
      either group. CONCLUSIONS: The DHCA induces less injury on pulmonary surfactant
      metabolism and pulmonary function than DHLF.

PMID- 16798204
TI  - Venoarterial extracorporeal membrane oxygenation (VA-ECMO) in pediatric cardiac
      support.
AB  - BACKGROUND: Resuscitation extracorporeal membrane oxygenation (R-ECMO) was
      introduced at our institution in July 2002. We reviewed the use of venoarterial
      (VA)-ECMO for cardiac diagnoses at our institution. METHODS: Retrospective
      analysis of patients on VA-ECMO for cardiac failure was performed. Survival was
      defined as discharge from hospital. RESULTS: Twenty-seven patients were supported
      with VA-ECMO (median age, 27 days; range, 1 to 640 days; median weight, 3.8 kg;
      range, 1.8 to 11.3 kg). Diagnoses were cardiomyopathy-myocarditis (CMM) in 8
      (30%), systemic-to-pulmonary artery shunt-dependent single ventricle (SV) in 12
      (44%), postcardiotomy for biventricular repair (BiV) in 6 (22%), and arrhythmia
      in 1 (4%). Sixteen of 27 patients survived (59%). Seven of 8 CMM patients
      survived (88%); 6 (75%) bridged to cardiac recovery, 1 to transplant (13%), and 1
      death (13%). Seven of 12 SV patients survived (58%). The SV ECMO indications:
      post-Norwood ventricular dysfunction (n = 3, 2 deaths), postoperative cardiac
      failure (n = 6, 2 deaths), respiratory failure (n = 1, 1 death), and acute shunt
      occlusion (n = 2, 0 deaths). One of 6 BiV patients survived (17%). The BiV ECMO
      indications: failure to wean from CPB (n = 3, 3 deaths), postoperative cardiac
      failure (n = 2, 2 deaths), and pulmonary hypertension (n = 1, 0 deaths). Fifteen
      patients (56%) underwent cardiopulmonary resuscitation during ECMO cannulation.
      Eleven of 15 R-ECMO patients (73%) survived versus 5 of 12 non-R-ECMO patients
      (42%, p = 0.13). Median duration of R-ECMO: 66 hours (range, 18 to 179) versus
      145 hours (range, 43 to 986, p = 0.01) for non-R-ECMO. CONCLUSIONS: Resuscitation
      extracorporeal membrane oxygenation is an appropriate application in pediatric
      patients with cardiac disease. Single ventricle patients experiencing
      cardiopulmonary collapse and CMM patients have favorable outcomes. Failure to
      wean from CPB and postoperative ventricular failure are higher risk indications.

PMID- 16798205
TI  - Analysis of surgical outcome in complex double-outlet right ventricle with
      heterotaxy syndrome or complete atrioventricular canal defect.
AB  - BACKGROUND: Double-outlet right ventricle encompasses a broad spectrum of
      anomalies. Heterotaxy syndrome, which is often associated with total anomalous
      pulmonary venous connection and complete atrioventricular canal defect, has been
      considered a risk factor for surgical repair of double-outlet right ventricle.
      METHODS: From January 1992 to May 1999, medical records of 96 patients (50 males,
      46 females) who had complex double-outlet right ventricle with heterotaxy and/or
      complete atrioventricular canal defect were reviewed (median age at initial
      surgery 3 months). Seventeen patients were neonates requiring surgery. Follow-up
      ranged from 1 day to 7.4 years (median, 16 months). RESULTS: Sixty-eight patients
      had heterotaxy syndrome (27 with total anomalous pulmonary venous connection).
      Eighty-three had complete atrioventricular canal defect, 22 with moderate to
      severe atrioventricular valve regurgitation at the time of surgical repair. Eight
      patients had two-ventricle repair, and 88 patients were considered for single
      ventricle management (bidirectional Glenn, 37; Fontan, 44). One patient had heart
      transplantation after bidirectional Glenn. There were 16 deaths including 10
      early (<30 days postoperatively). Overall survival (95% confidence interval)
      estimated by the Kaplan-Meier method was 89% (83% to 96%) at 1 month, 84% (76% to
      91%) at 1 year, and 81% (73% to 89%) at 5 years. Multivariate analysis revealed
      that neonatal presentation requiring surgery (p < 0.0001), moderate to severe
      atrioventricular valve regurgitation (p = 0.03), and pulmonary venous obstruction
      (p = 0.02) were risk factors for death. CONCLUSIONS: Atrioventricular valve
      regurgitation, pulmonary venous obstruction, and neonatal presentation are risk
      factors for mortality in patients with complex double-outlet right ventricle.
      Early surgical intervention in symptomatic neonates and infants, including those
      with pulmonary venous obstruction, may reduce mortality and improve outcome after
      staged operation.

PMID- 16798206
TI  - Clinical implications of major aortopulmonary collateral arteries in patients
      with right isomerism.
AB  - BACKGROUND: The presence of major aortopulmonary collateral arteries (MAPCA) in
      patients with right isomerism may alter the prognosis, which is still unclear.
      METHODS: From 1994 to 2003, 138 out of 155 patients (89%) with right isomerism
      had pulmonary stenosis or pulmonary atresia and constituted the study population.
      RESULTS: Two groups of patients were identified, one with MAPCA and the other
      without. The MAPCA originating from descending thoracic aorta or aortic arch was
      noted in 9 patients (6.5%), with a median number of MAPCA being 3 (range, 2 to
      4). Patients with MAPCA commonly had congestive heart failure (8/9, 89%) and
      frequent lower airway infection (6/9, 67%). In comparison with patients with
      MAPCA and without, the intrapericardial pulmonary artery was more frequently
      absent (2 of 9 vs 1 of 129, p < 0.001), and the pulmonary arterial size was
      smaller (McGoon ratio <1.5, 8 of 9 vs 57 of 129, p = 0.009) in the MAPCA group.
      The mean pulmonary arterial pressure measured was often higher than the suggested
      limit for Fontan circulation. Major aortopulmonary collateral arteries were
      addressed at a median of 6 months old (2 to 19 months old) in 5 patients.
      Although surgical mortality was not different for first-stage palliation and
      Glenn shunt in both groups, total cavopulmonary connection could only be
      performed in one patient with MAPCA with poor results. However, the 5-year
      survival of patients with and without MAPCA was not statistically different
      (74.1% vs 55.2%, p = 0.19). CONCLUSIONS: The presence of MAPCA was uncommon but
      still noted in patients with right isomerism. It may cause heart failure and a
      less favorable pulmonary vasculature for a complete Fontan-type operation.

PMID- 16798207
TI  - Repair of coarctation of the aorta in infants weighing less than 2 kilograms.
AB  - BACKGROUND: We retrospectively reviewed our experience in aortic coarctation
      repair on infants weighing less than 2 kg to evaluate the results and assess the
      rate of recoarctation in this group of patients. METHODS: Twenty-four consecutive
      babies weighing 2 kg or less were operated on over a period of 15 years. Median
      gestational age was 33 weeks (range, 30 to 36), and median weight was 1.6 kg
      (range, 1.0 to 2.0). Seventeen of them had associated cardiac anomalies. The
      methods of repair undertaken were resection with extended end-to-end anastomosis
      (n = 13), subclavian flap angioplasty (n = 9), carotid flap angioplasty (n = 1),
      and patch repair using pulmonary homograft tissue (n = 1). RESULTS: Mean follow
      up was 52.5 months (range, 0.5 to 151). There were 3 in-hospital deaths and 2
      late deaths. Recoarctation developed in 7 babies. Four underwent balloon
      dilatation; 1 of them required further surgery; 3 others have mild recoarctation,
      but have not required further intervention. Risk factor analyses revealed that
      the presence of preoperative congestive cardiac failure, and coexisting
      noncardiac lesions as well as the duration of descending aortic cross-clamp and
      postoperative ventilation had a significant influence on mortality after repair.
      CONCLUSIONS: Coarctation repair in infants less than 2 kg can be performed
      safely. The incidence of recoarctation is acceptable and comparable with that of
      other pediatric cohorts that have been reported. Preoperative cardiac function
      and associated noncardiac lesions may influence the incidence of mortality after
      repair. Delaying the timing of surgical repair to achieve growth is not
      necessary.

PMID- 16798208
TI  - Current assessment of mortality rates in congenital cardiac surgery.
AB  - BACKGROUND: The purpose of this study is to evaluate whether published and widely
      quoted mortality rates for pediatric cardiac surgery accurately reflect current
      expectations. Our hypotheses are that (1) mortality rates at high-quality
      pediatric cardiac programs are lower than published national results despite (2)
      a change in case mix with a shift away from low complexity operations. METHODS:
      We requested data for all pediatric cardiac surgical procedures performed between
      2001 and 2004 at 29 Congenital Heart Surgeon's Society (CHSS) member institutions
      (using CHSS as a surrogate for recognized high quality). Procedures were
      categorized by Risk Adjustment for Congenital Heart Surgery, version 1 (RACHS-1)
      category. In-hospital mortality rates for each category were calculated and
      compared with those in the 2002 manuscript of Jenkins and colleagues. RESULTS: We
      received data for 16,805 procedures from 11 institutions. In all, 12,672
      operations (76%) could be placed into RACHS-1 categories. Overall in-hospital
      mortality for categorized operations was 2.9% and was most related to case mix.
      There was a significant decrease in the percentage of category 1 operations, and
      there were significant increases in category 2, 4, and 6 operations. There were
      significant decreases in category 2, 3, 4, and 6 mortality rates (Jenkins 2002
      [CHSS]): (1) 0.4% [0.7%], (2) 3.8% [0.9%], (3) 8.5% [2.7%], (4) 19.4% [7.7%], (5)
      not applicable, and (6) 47.7% [17.2%]. There was no significant association
      between hospital surgical volume and mortality. CONCLUSIONS: This outcomes
      "footprint" suggests that we could hold ourselves accountable to higher
      benchmarks than those reflected by some published standards. Mortality rates
      declined, despite an increase in case mix complexity. The lack of association
      between hospital surgical volume and mortality suggests that other factors
      determine outcomes at high-quality institutions. In addition to continually
      validating our expectations for treatment, future research needs to identify
      these factors by understanding the system of care and identifying process
      measures that influence outcomes.

PMID- 16798209
TI  - Myocardial metabolism is better preserved after blood cardioplegia in infants.
AB  - BACKGROUND: We have previously reported improved hemodynamic function after blood
      cardioplegia in comparison with crystalloid cardioplegia. Furthermore, lactate
      was released from the heart after crystalloid cardioplegia but not after blood
      cardioplegia. The purpose of this study was to determine whether the difference
      in substrate metabolism between the two cardioplegia methods was restricted to
      lactate, or whether the difference in metabolic derangement was more extensive.
      METHODS: Thirty consecutive infants with complete atrioventricular septal defects
      were included in this prospective, randomized, controlled study. Arterial and
      coronary sinus blood concentrations of substrates and amino acids were measured
      after weaning from bypass. RESULTS: After crystalloid cardioplegia, there was a
      myocardial uptake of glutamate (p = 0.003), leucine (p = 0.03), lysine (p =
      0.003), and beta-hydroxybutyrate (p = 0.004), whereas lactate was released (p =
      0.03). After blood cardioplegia, there was a myocardial uptake of free fatty
      acids (p = 0.01) but no uptake of amino acids and no release of lactate.
      CONCLUSIONS: There are differences in myocardial substrate metabolism between
      blood cardioplegia and crystalloid cardioplegia, which involve carbohydrates and
      amino acids. The differences may include lipids but our data in this respect are
      not conclusive.

PMID- 16798210
TI  - Early graft failure of small-sized porcine valved conduits in reconstruction of
      the right ventricular outflow tract.
AB  - BACKGROUND: The quest for an alternative to homografts for reconstruction of the
      right ventricular outflow tract is ongoing. The Shelhigh No-React (NR-4000PA
      series) treated porcine pulmonic valve conduit (SPVC) was developed as a
      potential alternative. METHODS: During a 12-month period from May 2004 to May
      2005, the SPVC was implanted in 34 patients, of whom 62% were younger than 1
      year. Median age at operation was 7 months (range, 5 days to 12 years). Thirteen
      SPCV conduits size 10, 11 size 12, 8 size 14, and 2 size 16 were initially
      implanted. Since May 2005, however, we have temporarily abandoned its
      implantation as we were concerned about a number of early failures. RESULTS:
      Until November 2005, 1 early and 1 late death have occurred. Both were not
      conduit related. Fifteen conduits were replaced in 13 patients. Of these, 10 were
      size 10, 3 size 12, 2 size 14, and none size 16. Mean time to replacement of the
      SPVC was 313 +/- 116 days. A pseudointimal peel formation and chronic
      inflammation with foreign-body reaction was found in all explanted conduits at
      all levels. The maximum of the inflammatory reaction occurred at the valvular
      level around the porcine tissues, with shrinkage of the valve and hemodynamic
      compromise. At valvular level, small punctuate calcifications were observed in 2
      cases. In 6 patients an acute inflammatory component was observed. At late follow
      up (mean follow-up 366 +/- 102 days, 34 patient-years), echocardiography showed a
      mean graft gradient of 39.8 +/- 29.7 mm Hg, with mild to moderate insufficiency
      in 4 patients. CONCLUSIONS: Although the No-React treated valve largely resists
      calcification, pseudointimal peel formation was found in all explanted conduits
      and led to multilevel conduit stenoses. The small-sized SPVC can not be regarded
      as an ideal conduit for right ventricular outflow tract reconstruction.

PMID- 16798211
TI  - Invited commentary.

PMID- 16798212
TI  - Surgical treatment of aberrant right subclavian artery (arteria lusoria) aneurysm
      using three different methods.
AB  - BACKGROUND: Here we report our surgical experiences with aberrant right
      subclavian artery (ARSA) aneurysm in 8 patients. METHODS: Eight patients
      underwent surgical treatment for ARSA aneurysm between March 1994 and June 2005.
      The age of these patients ranged from 20 to 75 years. The mean size of the ARSA
      aneurysm was 3.3 cm, ranging from 2 to 5 cm. The ARSA aneurysm was completely
      resected through a left posterolateral thoracotomy after reconstruction of the
      right subclavian artery through the supraclavicular approach in 4 patients (group
      1). The ARSA aneurysm was excluded through a left posterolateral thoracotomy
      without revascularization of the right subclavian artery in 2 patients (group 2).
      The distal site of the ARSA aneurysm was closed followed by revascularization
      through a median sternotomy, and the ARSA aneurysm was left as a blind sack in 2
      patients (group 3). RESULTS: None of the patients in group 1 or 3 had any
      postoperative complications. In group 2, 1 had a steal syndrome caused by the
      exclusion of the ARSA aneurysm, and the other died of sepsis 2 months after the
      operation. CONCLUSIONS: Complete anatomical repair of the ARSA aneurysm could be
      performed through the combination of the supraclavicular approach and the left
      posterolateral thoracotomy, with excellent results. Exclusion of the ARSA
      aneurysm without revascularization resulted in a suboptimal outcome. Surgical
      results of simple closure of the ARSA followed by revascularization were
      uneventful, but the ARSA aneurysm was left as a blind sack.

PMID- 16798213
TI  - Surgical approach to left ventricular inflow obstruction due to dilated coronary
      sinus.
AB  - BACKGROUND: Left superior vena cava draining to a dilated coronary sinus can
      cause left ventricular inflow obstruction. Our purpose is to report 4 severely
      ill patients with this malformation who were operated upon and in whom repair was
      accomplished using an original surgical approach. METHODS: An operative procedure
      was designed, which included complete resection of the wall of the coronary sinus
      along its entire extension in the left atrium; division of the left superior vena
      cava; and establishment of the left superior vena cava-right atrial continuity by
      a wide left superior vena cava-right atrial appendage anastomosis. The series
      included 1 patient with interrupted inferior vena cava-hemiazygous continuation
      to left superior vena cava. RESULTS: There were no deaths. Absence of residual
      left ventricular inflow obstruction was demonstrated at follow-up in all cases,
      together with an unobstructed left superior vena cava-right atrial appendage
      right atrial connection. CONCLUSIONS: A predictable relief of the left
      ventricular inflow obstruction, together with preservation of an adequate
      drainage for the systemic venous return, were both achieved with this repair.

PMID- 16798214
TI  - Invited commentary.

PMID- 16798216
TI  - Lung-volume reduction surgery as an alternative or bridging procedure to lung
      transplantation.
AB  - BACKGROUND: In this study, we prospectively analyzed the functional outcome and
      the survival after lung-volume reduction surgery (LVRS) in patients with end
      stage emphysema who were initially potential candidates for lung transplantation
      (LTX), and investigated the impact of LVRS on posttransplant course in patients
      who underwent LTX after LVRS. METHODS: Of the 216 patients who underwent LVRS
      between 1994 and 2005, 58 were potential candidates for LTX at the time of LVRS
      (age 65 years or younger, forced expiratory volume in 1 second 25% of predicted
      or less; LVRS/LTX group). Lung-volume reduction surgery was performed by means of
      video-assisted, bilateral stapled resection of target areas. During the same
      period, 31 patients underwent primary LTX for end-stage emphysema (LTX group).
      Spirometry, plethysmography, carbon monoxide diffusing capacity, 6-minute walking
      distance, and dyspnea score were assessed preoperatively and at predetermined
      times after operation. Survival analysis was performed by use of the Kaplan-Meier
      method. RESULTS: All the functional variables significantly improved after LVRS
      and peaked within the first year. Subjective improvement was observed for up to 5
      years after LVRS, and 53% (31 of 58) of the patients were still alive and had not
      undergone transplantation after a median follow-up of 44 months. Fourteen percent
      (8 of 58) of the patients underwent secondary LTX because of progressive
      worsening of the respiratory function after a median bridging time between LVRS
      and LTX of 33 months. Postoperative recovery after transplantation and median
      survival time were comparable between the 8 patients of the LVRS/LTX group and
      the 31 patients of the LTX group (96.5 months versus 118.5 months, p = 0.9).
      CONCLUSIONS: Lung-volume reduction surgery can significantly improve symptoms and
      lung function in selected patients who are initially potential candidates for
      LTX. Lung-volume reduction surgery can allow the postponement of LTX for up to 4
      to 5 years and does not impair the chances for a subsequent successful LTX.

PMID- 16798217
TI  - Thoracoscopic lobectomy: a safe and effective strategy for patients receiving
      induction therapy for non-small cell lung cancer.
AB  - BACKGROUND: Thoracoscopic lobectomy is an accepted oncologic approach for early
      stage non-small cell lung cancer (NSCLC). We conducted a retrospective study of
      patients who underwent lobectomy after induction therapy to determine the
      feasibility of thoracoscopic lobectomy compared with conventional thoracotomy
      lobectomy. METHODS: The outcomes of 97 consecutive patients with NSCLC who
      received induction therapy followed by lobectomy from 1996 to 2005 were reviewed.
      Outcome variables analyzed included complete resection, chest tube duration,
      length of hospitalization, 30-day mortality, hemorrhage, pneumonia, respiratory
      failure, and other major complications. The Student t test and chi2 or RxC
      contingency tables were used to compare continuous and categoric variables,
      respectively. RESULTS: Lobectomy was performed by thoracotomy in 85 patients and
      thoracoscopically in 12 patients (1 conversion), with complete resection in all
      patients. All patients received induction chemotherapy, and 74 (76%) received
      induction radiotherapy as well: 66 of 85 (78%) in the thoracotomy group and 8 of
      12 (67%) in the thoracoscopy group. The overall median survival was 2.3 years,
      with no difference between the groups. Patients undergoing a thoracoscopic
      lobectomy had a shorter median hospital stay (3.5 vs 5 days, p = 0.0024) and
      chest tube duration (2 vs 4 days, p < 0.001). There were no significant
      differences in 30-day mortality, hemorrhage, pneumonia, or respiratory failure.
      CONCLUSIONS: Thoracoscopic lobectomy is a feasible approach for selected patients
      undergoing resection after induction therapy, and is associated with shorter
      hospital stay and chest tube duration. Long-term follow-up of survival will
      determine the role of thoracoscopic lobectomy in the management of patients after
      induction therapy.

PMID- 16798218
TI  - Lung cancer staging: a case for a new T definition.
AB  - BACKGROUND: The purpose of this study is to determine a more refined T definition
      for lung cancer staging on the basis of clinical outcomes. METHODS: The Walter
      Reed Army Medical Center Tumor Registry and the Thoracic Surgery Tumor Clinic
      files were queried for lung cancers diagnosed from 1990 to 2000. Cox regression
      analysis and Kaplan-Meier survival curves for tumor size were used to analyze the
      impact of size on survival and relative risk, and then used to redefine T. Using
      the new T definition, the cohort was restaged, and the two staging system
      survivals were compared using Cox regression analysis. RESULTS: Tumor size was
      documented in 439 males and 226 females. Forty-two tumors were 1.0 cm or less,
      133 were between 1.01 and 2.0 cm, 133 were between 2.01 and 3.0 cm, 91 were
      between 3.01 and 4.0, 96 were between 4.01 and 5.0, and 166 were greater than 5.0
      cm. A survival advantage was noted for smaller lesions, with 5-year survivals of
      48.6%, 45.9%, 26.6%, 27.0%, 14.4%, and 11.6%, respectively. Cox regression
      analysis revealed increased risk at 2.0 cm (hazards ratio, 2.014; 95% confidence
      interval, 1.24 to 3.26), 4.0 cm (hazards ratio, 2.51; 95% confidence interval,
      1.53 to 4.09), and 5.0 cm (hazards ratio, 3.14; 95% confidence interval, 1.96 to
      5.02). After redefining T, the new staging system showed a better 5-year survival
      in each stage. CONCLUSIONS: Lung cancer tumor size criteria should be changed to
      include T1 tumors 2.0 cm and less; T2 tumors between 2.0 and 4.0 cm or pleural
      invasion of T1 tumor; T3 tumors greater than 4.0 cm or pleural invasion of T2
      tumors.

PMID- 16798219
TI  - Pneumonectomy after high-dose radiation and concurrent chemotherapy for nonsmall
      cell lung cancer.
AB  - BACKGROUND: Pneumonectomy after high-dose radiotherapy and concurrent
      chemotherapy has been associated with high operative mortality. Therefore, most
      induction protocols limit radiation to 5,000 cGy or less. Additionally, the
      safety of right pneumonectomy after induction therapy has been questioned. The
      feasibility of pneumonectomy after high-dose radiotherapy and concurrent
      chemotherapy is reviewed. METHODS: From 1990 to 2005, 30 patients with locally
      advanced nonsmall-cell lung cancer underwent pneumonectomy after 5,940 cGy of
      radiation and two cycles of etoposide and cisplatin. To minimize
      postpneumonectomy pulmonary edema, patients were treated with a protocol that
      included fluid restriction and 48 hours of mechanical ventilation. Morbidity,
      mortality, and survival were examined. RESULTS: There were 18 right and 12 left
      pneumonectomies. Death occurred in 4 patients (13.3%) but in only 1 (5.6%) after
      right pneumonectomy. Causes of death included aspiration, bronchopleural fistula,
      pneumonia, and massive pulmonary embolus. Major morbidity occurred in 5
      (pneumonia in 2 and aspiration in 3). Median hospital stay was 9 days (range, 2
      to 45), and intensive care unit stay was 2 days (range, 2 to 35). Median overall
      survival was 22 months with a 5-year survival of 33%. Patients surviving
      operation had a median survival of 33 months and a 5-year survival of 38%.
      CONCLUSIONS: The mortality rate after pneumonectomy after high-dose radiation and
      concurrent chemotherapy is relatively high but results in significant survival.
      The mortality rate is not increased after right-sided operations. Pneumonectomy
      should continue to be offered to patients with advanced locoregional disease
      after induction high-dose radiotherapy and concurrent chemotherapy when a
      complete resection cannot be carried out with a lesser procedure.

PMID- 16798220
TI  - Fall in diffusing capacity associated with induction therapy for lung cancer: a
      predictor of postoperative complication?
AB  - BACKGROUND: Pulmonary resection after induction therapy is associated with high
      rates of pulmonary morbidity and mortality. However, the impact of induction
      therapy on the pulmonary toxicity and associated pulmonary complications has not
      been fully investigated in the setting of lung cancer surgery. METHODS: We
      assessed the 66 consecutive patients who underwent a pulmonary resection after
      induction therapy, 48 of whom received chemoradiotherapy and 18, chemotherapy
      alone. Results of pulmonary function before and after induction therapy were
      compared, and logistic regression analyses utilized to explore the risk factors
      of pulmonary morbidity. RESULTS: After induction therapy, forced expiratory
      volume in 1 second (FEV1) was increased significantly (from 2.28 +/- 0.61 L to
      2.40 +/- 0.62 L; p < 0.05); however, percent vital capacity (%VC) and FEV1/FVC
      did not change significantly. The diffusing capacity of lung for carbon monoxide
      (D(LCO)) was decreased significantly by 21% (from 90.3% +/- 18.3% to 71.1% +/-
      12.5%; p < 0.0005). Patients with respiratory complication showed lower predicted
      postoperative %FEV1 (49.5% +/- 11.1% versus 57.2% +/- 14.2%; p = 0.031) and
      predicted postoperative %Dlco (41.9% +/- 8.0% versus 55.4% +/- 10.1%; p < 0.0001)
      results than those without complications. Univariate and multivariate analyses
      revealed that predicted postoperative %D(LCO) alone was an independent factor to
      predict postoperative pulmonary morbidity. CONCLUSIONS: For patients who undergo
      a pulmonary resection after induction therapy, predicted postoperative %D(LCO) is
      more important to predict pulmonary morbidity rather than static pulmonary
      function (predicted postoperative %VC or %FEV1). The decrease in D(LCO) is
      thought to reflect a limited gas exchange reserve, caused by the potential
      toxicity of chemotherapy or chemoradiotherapy. We believe that the impact of
      diffusion limitation after induction therapy should to be emphasized to decrease
      the pulmonary morbidity.

PMID- 16798222
TI  - Expression of nuclear factor-kappaB and its clinical significance in nonsmall
      cell lung cancer.
AB  - BACKGROUND: It has been known that transcription factor nuclear factor (NF)
      kappaB plays an important role in cell proliferation and oncogenesis. The aims of
      this study were to evaluate expression levels of NF-kappaB in nonsmall-cell lung
      cancer (NSCLC) and to elucidate its clinical significance and prognostic value
      for patients with NSCLC. METHODS: Using 45 tumor tissue specimens from 45
      patients with NSCLC who underwent surgery, we investigated the expression of NF
      kappaB using Western blotting analysis. Apoptotic rate of NSCLC cells with
      different expression of NF-kappaB was determined by TUNEL (terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling) assay.
      Paraffin-embedded tissue blocks from 71 consecutive patients with NSCLC were
      obtained for immunohistochemical staining. RESULTS: The expression level of NF
      kappaB in poorly or moderately differentiated lung cancer cells was higher than
      that in well-differentiated ones (p = 0.001). The apoptotic rate was lower for
      lung cancer cells with higher NF-kappaB expression than for those with lower NF
      kappaB expression (p = 0.0238). Furthermore, expression of NF-kappaB was
      correlated with caspase-3, cyclooxygenase-2, and p53 expression in lung cancer
      cells that were examined. Most NSCLC cells showed nuclear staining pattern and
      the nuclear positive rate was 67.6% (48 of 71 specimens). Immunohistochemical NF
      kappaB expression in patients with NSCLC was an independent prognostic factor for
      overall survival. CONCLUSIONS: The results of this study suggest that expression
      of NF-kappaB may correlate with lung cancer differentiation. Overexpression of NF
      kappaB inhibits tumor cell apoptosis and indicates an unfavorable prognosis for
      overall survival in some patients with NSCLC.

PMID- 16798221
TI  - Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell
      lung cancer patients.
AB  - BACKGROUND: Sentinel lymph node identification has been tested in lung cancer
      patients with conflicting results. The present study was designed to assess the
      sensitivity, negative predictive value, and accuracy of intraoperative sentinel
      lymph node mapping by means of a radio-guided method in patients with nonsmall
      cell lung cancer to find the most appropriate definition of sentinel lymph node
      and to evaluate the usefulness of different particle sizes of radiocolloid.
      METHODS: One hundred ten patients with clinically N0 nonsmall cell lung cancer
      were enrolled in the pilot study of intraoperative sentinel node identification.
      Four quadrants of the peritumoral tissue were injected with 2 mL of 0.5 mCi
      technetium-99m suspension. Four radiocolloids of different particle size were
      used. After complete lymphadenectomy, all resected lymph nodes were examined with
      hematoxylin-eosin staining. All sentinel nodes negative for metastases by routine
      staining were searched further for metastatic deposits with both serial sections
      and immunohistochemistry for cytokeratins. RESULTS: The radio-guided method had a
      high identification rate, a high sensitivity, and a high negative predictive
      value (100%, 87%, and 93%, respectively) when immunohistochemistry was
      considered. When standard hematoxylin and eosin staining was applied, sensitivity
      and negative predictive value of sentinel lymph node labeling was lower (74% and
      89%, respectively). No significant differences were found in either the
      sensitivity or negative predictive value among the colloid solutions of different
      particle size used in radio labeling, although smaller particles have shown a
      tendency to produce better results. CONCLUSIONS: The radio-guided technique
      provides efficient sentinel lymph node identification in lung cancer. Further
      studies are warranted to confirm the clinical utility of this strategy.

PMID- 16798223
TI  - Invited commentary.

PMID- 16798225
TI  - Prediction of prognosis and surgical indications for pulmonary metastasectomy
      from colorectal cancer.
AB  - BACKGROUND: Treatment of pulmonary metastases from colorectal cancer by excision
      has increased rapidly, but reports on indications and prognostic factors are
      inconsistent. We sought to identify poor prognostic factors preoperatively and to
      retrospectively evaluate preoperative clinical indications for surgery. METHODS:
      A total of 75 patients with colorectal cancer had pulmonary metastases excised
      from 1986 to 2003. Tumor size, number, laterality, hilar or mediastinal
      lymphadenopathy, and carcinoembryonic antigen level were possible risk factors
      for metastatic tumors, with primary site of colorectal tumor, disease-free
      interval, and hepatectomy for liver metastasis possible risk factors for primary
      tumors. Prognostic factors in univariate and multivariate analyses also included
      age and sex. RESULTS: Five-year survival rates were 41.3% after pulmonary
      excision and 73.1% after primary colorectal resection. Three factors identified
      as significant by univariate log-rank test for overall survival after pulmonary
      resection were carcinoembryonic antigen (p < 0.0001), tumor laterality (p =
      0.0205), and number of pulmonary metastases (p = 0.0028). Multivariate analysis
      found that carcinoembryonic antigen, tumor number, tumor size, and patient's age
      were also independent prognostic factors. In contrast, carcinoembryonic antigen,
      number of metastases, and disease-free interval predicted prognosis after primary
      colorectal resection. Prior hepatectomy for metastases did not influence
      prognosis after pulmonary metastasectomy. CONCLUSIONS: Elevated carcinoembryonic
      antigen level and multiple metastases are preoperative predictors of poor
      prognosis after resection of pulmonary metastases from colorectal cancer.
      Survival rate is sufficient to justify pulmonary metastasectomy if there is no
      local or distant metastatic lesion other than in the liver; if needed, sequential
      pulmonary and hepatic metastasectomy can be performed.

PMID- 16798224
TI  - Inhibition of retinoblastoma tumor suppressor activity by RNA interference in
      lung cancer lines.
AB  - BACKGROUND: Inactivation of retinoblastoma (RB) tumor suppressor function occurs
      frequently in lung cancer. Short-hairpin RNA can be constructed to target
      specific sequences and efficiently knock down protein expression. We developed a
      short-hairpin RNA approach to specifically target Rb in lung cancer cells to
      determine the influence of RB knockdown on proliferation. METHODS: NCI-H520 human
      lung cancer cells (wild-type Rb) were transfected with pMSCVpuro-Rb3C, a plasmid
      containing a short-hairpin sequence targeted to human Rb. Transfectants harboring
      the construct were selected with puromycin. Loss of RB expression in selected
      cell populations was determined by immunoblotting. Proliferating cells were
      counted to establish growth rates. Retinoblastoma-proficient and RB-deficient
      tumor growth was monitored in nude mice. RESULTS: Transfection with pMSCVpuro
      Rb3C dramatically diminished RB expression and led to aberrant expression of RB
      regulated genes. Cells harboring pMSCVpuro-Rb3C grew at an increased rate
      compared with control cells: 480.6 +/- 37.7 versus 159.4 +/- 36.2 (relative cell
      count at 12 days). Tumor growth in nude mice also increased with RB knockdown
      compared with control mice: 135.2 +/- 73.6 mm3 versus 40.0 +/- 17.0 mm3 (tumor
      volume at 10 days). CONCLUSIONS: Inhibition of RB expression is efficiently
      achieved in lung cancer cells with short-hairpin RNA. Genetic targets of RB are
      deregulated with RB knockdown. Retinoblastoma depletion increases growth in vitro
      and in murine xenografts. These studies indicate that even in the context of an
      established tumor cell line, RB limits tumorigenic proliferation. Additionally,
      this model will serve as an ideal system to evaluate the role of RB activity on
      therapeutic response.

PMID- 16798227
TI  - Invited commentary.

PMID- 16798226
TI  - Mechanical ventilation and air leaks after lung biopsy for acute respiratory
      distress syndrome.
AB  - BACKGROUND: Open lung biopsy in acute respiratory distress syndrome (ARDS) may
      provide a specific etiology and change clinical management, yet concerns about
      complications remain. Persistent air leak is the most common postoperative
      complication. Risk factors in this setting are not known. METHODS: We performed a
      retrospective analysis of 53 patients who underwent open lung biopsy for clinical
      ARDS (based on American European Consensus Conference criteria) between 1989 and
      2000. RESULTS: Sixteen patients (30.2%) developed an air leak lasting more than 7
      days or died with an air leak. Univariate analyses showed no significant
      correlation with age, gender, sex, corticosteroid use, diabetes,
      immunocompromised status, or pathologic diagnosis. A lower risk of air leak was
      associated with lower peak airway pressure and tidal volume, use of pressure
      cycled ventilation, and use of an endoscopic stapling device. In multivariate
      analyses, only peak airway pressure remained a significant predictor. The risk of
      prolonged air leak was reduced by 42% (95% confidence interval [CI: 17% to 60%])
      for every 5 cm H2O reduction in peak airway pressure. CONCLUSIONS: The use of a
      lung-protective ventilatory strategy that limits peak airway pressures is
      strongly associated with a reduced risk of postoperative air leak after open lung
      biopsy in ARDS. Using such a strategy may allow physicians to obtain information
      from open lung biopsy to make therapeutic decisions without undue harm to ARDS
      patients.

PMID- 16798228
TI  - Uncommon primary tracheal tumors.
AB  - BACKGROUND: Primary tracheal tumors other than adenoid cystic or squamous cell
      carcinoma are uncommon and have a heterogeneous histologic appearance. The
      experience regarding their treatment and long-term outcome is limited, and
      alternatives to segmental tracheal resection, including endoscopic treatment or
      radiation, continue to be explored. METHODS: A retrospective analysis was
      performed of uncommon tracheal tumors among 360 primary tracheal tumors seen over
      40 years, excluding adenoid cystic and squamous cell carcinoma. RESULTS: Of 90
      patients, 34 (38%) had benign tumors and 56 malignant: 11 carcinoid tumors, 14
      mucoepidermoid carcinomas, 13 sarcomas, 15 nonsquamous bronchogenic carcinomas, 2
      lymphomas, and 1 melanoma. Three patients had a second tracheal malignancy.
      Dyspnea was the most common symptom in benign tumors and hemoptysis in malignant
      tumors. Twelve patients did not undergo tracheal resection (13.3%) and 1 died
      before resection. Surgical therapy in 77 patients (85%) consisted of laryngectomy
      in 3, laryngotracheal resection in 9, tracheal resection in 46, and carinal
      resection in 19. Hospital mortality was 2.6% (2 of 77 patients) and major
      complications occurred in 16% (12 of 77 patients). Mean follow-up was 9.7 years.
      After resection, survival at 10 years was 94% for benign and 83% for carcinoid
      tumors, and at 5 years survival was 60% for bronchogenic carcinoma, 100% for
      mucoepidermoid tumors, and 78% for sarcomas. Patients with lymphomas and melanoma
      are alive more than 8 years after resection. Ten patients experienced recurrence
      (14%). CONCLUSIONS: Surgical resection of uncommon primary tracheal tumors
      alleviates airway obstruction, is curative in patients with benign or slow
      growing malignant lesions, and prolongs survival in highly malignant lesions.

PMID- 16798229
TI  - Do expandable metallic airway stents have a role in the management of patients
      with benign tracheobronchial disease?
AB  - BACKGROUND: With increasing availability many centers are deploying expandable
      metallic stents to manage patients with diverse endobronchial disorders. Although
      these devices have an important role in malignant disease their usefulness in
      benign large airway disorders is less defined. METHODS: Between 1997 and 2005, 31
      patients aged 34 to 83 years with benign large airway compromise secondary to
      tracheomalacia (n = 7), posttracheostomy stricture (n = 8), posttracheostomy
      rupture (n = 2), postpneumonectomy bronchopleural fistula (n = 2), stricture
      after lung transplantation (n = 3), lobectomy, tuberculosis, traumatic injury to
      right main bronchus (n = 1 patient each), and external compression of the airway
      secondary to achalasia, multinodular goiter, aortic aneurysm, right
      brachiocephalic artery aneurysm, right interrupted aortic arch, and dissecting
      aneurysm (n = 1 patient each) who were medically unfit for formal surgical
      intervention were treated by Ultraflex stent deployment. The range of follow-up
      was 1 week to 96 months. Stents were deployed under anesthesia using rigid
      bronchoscopy. RESULTS: Complications included granulation tissue formation (n =
      11) treated with Nd: YAG laser ablation, stent migration (n = 1; stent removed,
      another deployed), metal fatigue (n = 1), stent removal (n = 1), mucus plugging
      (n = 2), and halitosis (n = 6) difficult to treat despite antibiotics. Thirteen
      patients died of unrelated causes between 1 week and 15 months after stent
      deployment. CONCLUSIONS: Endobronchial metallic stents should be considered only
      for selected patients with large airway compromise secondary to benign airway
      diseases for whom other medical comorbidities contraindicate formal airway
      surgery. Once deployed, they are difficult to remove, are associated with
      significant complications, and require prospective bronchoscopic surveillance and
      often further therapeutic intervention.

PMID- 16798215
TI  - Patient and surgical factors influencing air leak after lung volume reduction
      surgery: lessons learned from the National Emphysema Treatment Trial.
AB  - BACKGROUND: Although staple line buttressing is advocated to reduce air leak
      after lung volume reduction surgery (LVRS), its effectiveness is unknown. We
      sought to identify risk factors for air leak and its duration and to estimate its
      medical consequences for selecting optimal perioperative technique(s), such as
      buttressing technique, to preempt or treat post-LVRS air leak. METHODS: Detailed
      air leak data were available for 552 of 580 patients receiving bilateral stapled
      LVRS in the National Emphysema Treatment Trial. Risk factors for prevalence and
      duration of air leak were identified by logistic and hazard function analyses.
      Medical consequences were estimated in propensity-matched pairs with and without
      air leak. RESULTS: Within 30 days of LVRS, 90% of patients developed air leak
      (median duration = 7 days). Its occurrence was more common and duration prolonged
      in patients with lower diffusing capacity (p = 0.06), upper lobe disease (p =
      0.04), and important pleural adhesions (p = 0.007). Duration was also protracted
      in Caucasians (p < 0.0001), patients using inhaled steroids (p = 0.004), and
      those with lower 1-second forced expiratory volume (p = 0.0003). Surgical
      approach, buttressing, stapler brand, and intraoperative adjunctive procedures
      were not associated with fewer or less prolonged air leaks (p >/= 0.2).
      Postoperative complications occurred more often in matched patients experiencing
      air leak (57% vs 30%, p = 0.0004), and postoperative stay was longer (11.8 +/-
      6.5 days vs 7.6 +/- 4.4 days, p = 0.0005). CONCLUSIONS: Air leak accompanies LVRS
      in 90% of patients, is often prolonged, and is associated with a more complicated
      and protracted hospital course. Its occurrence and duration are associated with
      characteristics of patients and their disease, not with a specific surgical
      technique.

PMID- 16798230
TI  - Postpneumonectomy empyema: results after the Clagett procedure.
AB  - BACKGROUND: The purpose of this study was to analyze our experience with the
      management of patients with postpneumonectomy empyema treated by the Clagett
      procedure. METHODS: Data were analyzed from our prospective database on 84
      consecutive patients with postpneumonectomy empyema from July 1988 to June 2004.
      RESULTS: There were 73 men and 11 women. Median age was 62 years (range, 35 to
      77). Indications for pneumonectomy were malignancy in 77 patients and benign
      disease in 7. The pneumonectomy was done at our institution in 43 patients and
      elsewhere in 41. A right pneumonectomy was performed in 66 patients and a left in
      18. All patients were managed with the Clagett procedure consisting of open
      pleural drainage, serial operative debridements, and eventual chest closure after
      filling the pleural cavity with antibiotic solution. A bronchopleural fistula was
      present in 55 patients and was closed in all. A muscle flap was used to reinforce
      the bronchial stump in 60 patients (71%), 51 with a bronchopleural fistula, and 9
      without. Operative mortality was 7.1%. Median follow-up was 1.5 years (range, 0
      to 22). Overall, 81% of patients had a healed chest wall without evidence of
      recurrent infection. The bronchopleural fistula remained closed in all patients.
      Median overall survival was 3.4 years with a 5-year survival of 44.5%. Age less
      than 65 years and an interval between pneumonectomy and empyema of greater than
      15 weeks were independent predictors of improved long-term survival. CONCLUSIONS:
      The Clagett procedure remains safe and successful in the majority of patients
      with postpneumonectomy empyema. Age less than 65 years and a long interval
      between pneumonectomy and empyema are important determinants of outcome.

PMID- 16798231
TI  - Predictors of successful closure of open window thoracostomy for
      postpneumonectomy empyema.
AB  - BACKGROUND: Although the open window thoracostomy (OWT) represents the ideal
      method for drainage of postpneumonectomy empyema (PPE), several controversies
      exist concerning its closure. METHODS: Between January 1993 and December 2003, an
      OWT was created in 31 patients (29 male and 2 female) with PPE. The median age
      was 61 years (range, 32 to 76). In 26 patients (84%) a bronchial stump fistula
      developed. The OWT closure was correlated with characteristics of PPE and the
      timing of OWT. RESULTS: In 15 patients (48%), the OWT could be closed by
      obliteration of pleural cavity with antibiotic solution (3 patients) or
      intrathoracic muscle transposition (12 patients). A successful closure was
      observed in 13 of the 15 patients (87%). All patients closed by Clagett's
      procedure remained empyema free. Recurrent cancer (n = 4), poor functional status
      (n = 3), refusal of further operation (n = 2), and persistent tuberculous empyema
      (n = 2) were common causes of failure of OWT closure. Univariate analysis
      revealed that the timing of empyema development after surgery (p = 0.02) and the
      timing of OWT (p = 0.03) were significant predictors of thoracostomy closure.
      CONCLUSIONS: Late onset of PPE and immediate OWT creation are significant
      predictors of OWT closure. Smaller dimensions of the pleural cavity appeared to
      increase the likelihood of closure. When the pleural cavity shows healthy
      granulation tissue and no bronchopleural fistula, the Clagett's procedure is safe
      and effective to obliterate the pleural cavity. Obliteration by muscle flap
      transposition can be reserved for patients with persistent or recurrent
      bronchopleural fistula.

PMID- 16798233
TI  - Incidence and types of arrhythmias after mediastinal manipulation during
      transhiatal esophagectomy.
AB  - BACKGROUND: Transhiatal esophagectomy (THE) is a common operative procedure for
      carcinoma esophagus. Complications of this procedure include arrhythmias and
      hypotension during blunt dissection of the esophagus from posterior mediastinum.
      In the literature, exact incidence and type of arrhythmias have not been
      reported. We employed Holter monitoring during mediastinal manipulation in
      patients undergoing THE, for this purpose. METHODS: This prospective study was
      carried out in 20 consecutive American Society of Anesthesiologists grade I-II
      patients undergoing THE. Anesthetic technique included induction with thiopentone
      and maintenance with morphine, vecuronium, and isoflurane. In addition to routine
      parameters, Holter monitoring was undertaken to record the exact incidence and
      types of arrhythmias. "Premanipulation" or control period included duration of 30
      minutes preceding mediastinal manipulation, while "during manipulation" or study
      period included the duration of mediastinal manipulation. The incidence of
      arrhythmias was studied for 48 hours in the postoperative period. The Fisher
      exact test was applied to analyze incidence of arrhythmias and hypotension.
      RESULTS: Out of 20 patients, only 2 had arrhythmias in the premanipulation
      period, while 13 had arrhythmias during the manipulation period (p < 0.01).
      During the manipulation period, arrhythmias included supraventricular ectopics
      and ventricular ectopics in 2 patients each and a combination of both in 9
      patients. Arrhythmias were transient and had no correlation with either duration
      or degree of hypotension in all the patients. However, there was a linear
      relationship between hypotension and duration of mediastinal manipulation. Two
      patients (10%) had atrial arrhythmias in the postoperative period. CONCLUSIONS:
      In transhiatal esophagectomy, there is a significant incidence of both
      arrhythmias and hypotension during mediastinal manipulation. The incidence of
      arrhythmias can be minimized by limiting the duration of the manipulation. The
      incidence of postoperative arrhythmias was not significant.

PMID- 16798232
TI  - Erythropoietin-alfa during neoadjuvant chemotherapy for locally advanced
      esophagogastric adenocarcinoma.
AB  - BACKGROUND: In a previous study we showed that many patients with esophagogastric
      adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now
      investigated the role of erythropoietin in managing anemia during neoadjuvant
      chemotherapy. METHODS: Patients with esophagogastric adenocarcinoma who
      experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received
      erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were
      the response to erythropoietin, safety, the need for allogeneic red blood cell
      transfusion, and the rate of postoperative complications. RESULTS: Between April
      2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The
      mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin
      level before patients received erythropoietin was 11.5 g/dL. One year after
      involvement in the trial, 4 of 17 analyzable patients were still anemic
      (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and
      16 (73%) responded. We could observe a significant increase in hemoglobin
      concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two
      patients (8%) received allogeneic transfusions; the rate of postoperative
      complications was 16%. There were no erythropoietin-related adverse events.
      CONCLUSIONS: Treatment with erythropoietin is effective and well tolerated in
      patients with esophagogastric adenocarcinoma who experience anemia during
      neoadjuvant chemotherapy.

PMID- 16798235
TI  - Invited commentary.

PMID- 16798234
TI  - Experimental study of one-shot vascular anastomostic device for proximal vein
      graft anastomoses.
AB  - PURPOSE: A new type of sutureless aortic-vein-graft vascular anastomostic device,
      One-Shot Vascular Anastomostic Device (Horologe Factory of Jinan City, Shandong
      Province, China) has been recently designed to create a one-shot anastomosis
      between the aorta and vein grafts for coronary artery bypass grafting surgery.
      DESCRIPTION: Twelve pigs were scheduled for the test of the feasibility of the
      One-Shot Vascular Anastomostic Device for artery to vein graft anastomosis. In
      each animal one proximal anastomosis was performed by means of the One-Shot
      Vascular Anastomostic Device and the distal end was sutured in a conventional
      manner to serve as the animal own control. The anastomosis incorporating the
      abdominal main artery to the segment of a free external carotid vein to the
      external iliac artery is for the simulation of the aorta-vein anastomosis.
      EVALUATION: The mean duration of the completion of the proximal anastomosis was
      1.2 +/- 1.2 minutes (range, 0.3-5.0 minutes). There was a significant difference
      between the control groups (p < 0.01). All vein grafts were still functioning at
      the end of the procedure. Pathologic studies and angiography demonstrated that
      the results were satisfactory. CONCLUSIONS: This device enables rapid and safe
      completion of vascular anastomostic procedure. The vein graft was functioning
      well and incorporated into the vessel intima smoothly.

PMID- 16798236
TI  - Endovascular treatment of a thoracic aortic pseudoaneurysm after previous open
      repair.
AB  - The use of endovascular stents to treat descending thoracic aortic pathologies is
      emerging as a less invasive therapy to treat high-risk patients. This case report
      describes the presentation of a patient with a pulsatile mass on her back. The
      patient's computed tomographic scan revealed the mass to be an extension of a
      large psuedoaneurysm from the site of a previous repair of her thoracic aorta for
      a dissecting aneurysm several years earlier. The psuedoaneurysm was successfully
      treated with an endovascular stent and the patient was discharged home on
      postoperative day 5.

PMID- 16798237
TI  - Management of superior vena cava syndrome by internal jugular to femoral vein
      bypass.
AB  - We report a 30-year-old man with superior vena cava syndrome due to fibrosis from
      a previously irradiated malignant thymoma. The patient presented 4 years after
      the initial treatment, after having been lost to follow-up. Investigations
      revealed total obstruction of the superior vena cava, and right subclavian and
      right internal jugular vein. The patient underwent an extra-anatomic bypass
      (ringed polytetrafluoroethylene graft 10-mm diameter) between the left internal
      jugular vein and the left femoral vein brought in a subcutaneous tunnel over the
      anterior chest and abdominal wall. Entry to the thoracic cavity was avoided due
      to extensive fibrotic changes visualized in the computed tomographic chest scan.
      Follow-up Doppler at 2 months, 6 months, 1 year, and 3 years showed a patent
      graft. An internal jugular vein to the femoral vein bypass is a simple method for
      palliation of superior vena cava syndrome.

PMID- 16798238
TI  - OPCAB for acute LAD dissection due to blunt chest trauma.
AB  - A 40-year-old male pedestrian was hit by a truck and was admitted with multiple
      injuries including blunt chest trauma. Electrocardiogram revealed acute anterior
      ST-segment elevation and myocardial infarction. Coronary angiography demonstrated
      acute ostial left anterior descending coronary artery dissection. Due to extent
      and location, the lesion was not amenable for angioplasty. Multiple associated
      injuries and severely impaired coagulation studies directed us to perform
      emergency off-pump coronary artery bypass grafting.

PMID- 16798239
TI  - Two cases of chronic pulmonary thromboembolism saved by postoperative use of a
      percutaneous cardiopulmonary support device.
AB  - We performed pulmonary thromboendarterectomy under deep hypothermic intermittent
      circulatory arrest in 18 patients with chronic pulmonary thromboembolism from
      August 2001 to January 2004. In some of these cases, reperfusion pulmonary edema
      prevented a satisfactory improvement in hemodynamic data soon after the surgery.
      Here we report two cases of chronic pulmonary thromboembolism in which we
      successfully prevented postoperative persistent pulmonary hypertension and
      hypoxia caused by severe reperfusion pulmonary edema by the use of a percutaneous
      cardiopulmonary support device.

PMID- 16798240
TI  - Simple mechanical aortic valve closure in ventricular assist device recipients.
AB  - Patients with mechanical aortic valves that develop refractory heart failure may
      require left ventricular assist devices. These patients have an increased risk of
      postoperative thromboembolic events due to intermittent valve opening. Previously
      described techniques to address this problem can result in a significantly
      increased ischemic time. We describe a simple but novel technique to close the
      mechanical aortic prosthesis in an expeditious manner.

PMID- 16798242
TI  - Carney complex.
AB  - We report an illustrated case of a 61-year-old woman with multiple atrial myxomas
      and cutaneous hyperpigmentation as part of the Carney complex. The case is
      notable for an unusually late presentation in life and a strong family history of
      atrial myxomas and sudden death. The importance of regular life-long
      echocardiographic screening and surveillance in all family members of affected
      cases is emphasized.

PMID- 16798243
TI  - Supracardiac total anomalous pulmonary venous connection with a supramitral ring:
      a rare, surgically correctable anomaly.
AB  - Total anomalous pulmonary venous connection is rarely associated with a
      supramitral ring. This condition should be suspected in any infant having total
      anomalous pulmonary venous connection with obstruction to the pulmonary venous
      return. Preoperative echocardiography is usually successful in detecting the
      lesion. The Shumaker and King repair for total anomalous pulmonary venous
      connection is most appropriate for such composite lesions as it enables the
      surgeon to identify the membrane and excise it easily and completely. We report
      one such case.

PMID- 16798241
TI  - Coronary pseudoaneurysm: an unreported complication of Castleman's disease.
AB  - Castleman's disease is considered a benign disease with very few reports of local
      invasion into adjacent structures. We present the first reported case of
      myocardial involvement with Castleman's disease. Careful preoperative planning
      allowed the placement of a left ventricular assist device with eventual heart
      transplantation after complete resection of the tumor and unsuccessful myocardial
      revascularization.

PMID- 16798244
TI  - Detection of lower torso ischemia by near-infrared spectroscopy during
      cardiopulmonary bypass in a 6.8-kg infant with complex aortic anatomy.
AB  - Neonates and small infants with congenital heart disease and complex cardiac and
      vascular anatomy are particularly prone to episodes of complete or incomplete
      regional ischemia during cardiopulmonary bypass. These episodes may result either
      from inhomogeneous distribution of arterial blood flow via the aortic cannula or
      from impaired drainage of blood via the venous cannulae. However, techniques for
      continuous routine monitoring of regional perfusion in neonates or small infants
      undergoing cardiopulmonary bypass are extremely limited. Over recent years,
      transcranial near-infrared spectroscopy has become established as a useful
      technique for the non-invasive monitoring of cerebral oxygenation. Here we
      present a case in which simultaneous near-infrared spectroscopic monitoring of
      the oxygenation status in the brain and the right upper thigh revealed lower
      torso ischemia due to accidental cross-clamping of a hypoplastic descending aorta
      which would otherwise have been unnoticed. This shows that parallel near-infrared
      spectroscopy of the brain and the lower extremities may represent a novel non
      invasive monitoring technique to ensure adequate cerebral and extracerebral
      perfusion during cardiopulmonary bypass.

PMID- 16798245
TI  - Rapid diagnosis of cannula migration by cerebral oximetry in neonatal arch
      repair.
AB  - Although it has gained much interest in other surgical specialties, the
      application of near-infrared spectroscopy to assess cerebral perfusion during
      cardiac surgery is relatively new. Regional cerebral oxygen saturation (rSO2) is
      a function of cerebral oxygen supply and demand. Continuous monitoring of the
      rSO2 permits early detection of cerebral ischemia allowing for prompt
      intervention. The following is a description of a repair of truncus arteriosus
      with type A interrupted aortic arch during which continuous cerebral oximetry
      assisted with the positioning of the arterial cannula avoiding a prolonged
      episode of cerebral ischemia.

PMID- 16798246
TI  - Successful surgical resection of intrapericardial extralobar pulmonary
      sequestration with congenital pulmonary adenomatoid malformation type II.
AB  - We report a 7-day-old boy referred to our institution with tachypnea and
      cardiomegaly who was discovered to have an intrapericardial extra-lobar pulmonary
      sequestration containing a cystic pulmonary adenomatoid malformation type II. He
      underwent successful surgical resection of the intrapericardial mass, which we
      believe represents the first reported case of this rare entity.

PMID- 16798247
TI  - Bilateral communicating bronchopulmonary foregut malformations in a child.
AB  - Communicating bronchopulmonary foregut malformations are rare anomalies. The
      complex anatomy requires innovative surgical techniques. We report a child with
      bilateral sequestrations communicating with the lower esophagus. The
      sequestrations were excised through a single thoracotomy incision and the
      esophagus was repaired. Postoperatively the child has remained asymptomatic.

PMID- 16798248
TI  - Oklahoma prosthesis: resection of tumor of clavicle and chest wall reconstructed
      with a custom composite graft.
AB  - Tumors involving the clavicle by primary or metastatic growth may require
      clavicular resection often with rib resection. The resulting cosmetic and
      functional impairment of clavicular resection may be significant with a sloped
      appearing shoulder girdle and chronically impaired movement of the upper
      extremity. We report a 48-year-old woman presenting with a bulky metastatic renal
      cell mass of her left clavicle extending to the chest wall. We report en-bloc
      clavilculectomy and chest wall resection with a novel method of reconstruction
      using a single methyl methacrylate and prolene composite prosthesis in a
      configuration resembling the state of Oklahoma.

PMID- 16798249
TI  - Abdominal compartment syndrome: a rare complication of plication of the
      diaphragm.
AB  - Abdominal compartment syndrome is an increasingly recognized phenomenon. We
      report the case of an otherwise fit and healthy 42-year-old man who underwent
      plication of the right hemidiaphragm for idiopathic phrenic paresis. His
      postoperative recovery was complicated by abdominal compartment syndrome, which
      was managed conservatively. We believe this is the only report of this
      complication after diaphragmatic plication and one of very few reported thoracic
      causes of abdominal compartment syndrome.

PMID- 16798250
TI  - Acute exacerbation of interstitial fibrosis after pulmonary resection.
AB  - Idiopathic pulmonary fibrosis is a chronic diffuse lung disease of unknown cause,
      and a risk factor for increasing morbidity and mortality after lung resection.
      Acute exacerbation of idiopathic pulmonary fibrosis after lung surgery for lung
      cancer is rare. The outcome is unsatisfactory despite therapy. We report two
      cases of acute exacerbation of idiopathic pulmonary fibrosis after resection for
      lung cancer.

PMID- 16798252
TI  - Giant benign esophageal schwannoma requiring esophagectomy.
AB  - Benign esophageal schwannomas are rare tumors with only 14 cases reported in the
      English literature. All previous reports describe excision without major
      esophageal resection. We report the case of a 33-year-old woman with a giant
      esophageal schwannoma that required total thoracic esophagectomy.

PMID- 16798251
TI  - Treatment of cavitary pulmonary zygomycosis with surgical resection and
      posaconazole.
AB  - We describe a 57-year-old woman with acute lymphoblastic leukemia who had a
      cavitary lesion develop in the right upper lobe caused by Cunninghamella
      bertholletiae, a zygomycete. The infection was resistant to both high-dose
      liposomal amphotericin B and voriconazole. The current report demonstrates
      successful treatment, even in the setting of subsequent bone marrow
      transplantation and immunosuppression, using a combination of surgical resection
      and posaconazole therapy.

PMID- 16798253
TI  - Recurrent localized fibrous tumor of the pleura.
AB  - Localized fibrous tumors of the pleura are rare. They are often asymptomatic and
      may have symptoms based on size, bronchial invasion, or hormone production, or a
      combination of these. Complete resection offers the best chance of cure. However,
      recurrence is reported in a significant number of patients and can often be
      treated by repeated resection, albeit with increasing difficulty. We present a
      case in which delayed recurrence occurred after excision of such a tumor. This
      required a chest-wall resection and reconstruction after which a second
      recurrence occurred. Further thoracotomy including a latissimus dorsi free flap
      procedure was needed for a third-time recurrence.

PMID- 16798254
TI  - Surgical treatment of aortic isthmic coarctation with aortic aneurysmatic
      looping.

PMID- 16798255
TI  - Virtual angioscopy in type-A dissection: ascending aortic stent-graft repair.

PMID- 16798256
TI  - Simple and easy method for chordal reconstruction during mitral valve repair.
AB  - We describe a simple reproducible method for chordal replacement using expanded
      polytetrafluoroethylene sutures during a mitral valve repair. With this
      technique, fine length adjustments of the new chordae are easy to make and it is
      possible to tie the two ends of the suture securely without slippage.

PMID- 16798257
TI  - Extracardiac Fontan procedure bridging the vertebra for apico-caval
      juxtaposition.
AB  - For 5 patients with univentricular heart associated with apico-caval
      juxtaposition, an extracardiac Fontan procedure was carried out using an
      artificial graft bridging the vertebra to avoid graft compression by the vertebra
      and the ventricle. For 2 patients representing nonconfluency between the inferior
      caval vein and the hepatic vein, a hand-made, shoe-tree graft was used.
      Postoperatively all patients are doing well without a stenotic venous pathway.
      This extracardiac operation using an artificial graft bridging the vertebra may
      be advantageous for univentricular heart associated with apico-caval
      juxtaposition to prevent a postoperative stenotic venous pathway.

PMID- 16798258
TI  - Cost-effective endoscopic radial artery harvesting.
AB  - Radial artery harvesting has been routinely performed by endoscopy. We present a
      reduced cost technique using a reusable retractor and thermal welding shears. The
      combination of reusable and disposable tools allows patients to benefit from
      endoscopic radial artery harvesting with decreased morbidity and favorable
      cosmetic results.

PMID- 16798259
TI  - Partial sleeve right pneumonectomy with carinal flap closure.
AB  - We describe a technique used in 2 patients for resection of carcinoid tumor
      arising from the right main bronchus and extending along the lateral wall of the
      lower trachea. A flap was mobilized from the non-involved membranous posterior
      wall of the right main bronchus, which was left attached to the carina. This was
      used to close the defect in the lower trachea. Both patients did well after
      surgery and were followed-up for 10 to 17 years with no evidence of recurrence.

PMID- 16798260
TI  - Current strategies in the management of atrial fibrillation.
AB  - Treatment of atrial fibrillation (AF) has been undergoing significant changes
      recently. This is due partly to different mechanisms proposed for persistent and
      permanent AF and partly due to the introduction of energy-based techniques,
      providing less invasive procedures. This article aims to review the mechanisms of
      AF leading to the changes in clinical practice and to review the results of
      surgery, energy-based, and percutaneous techniques. It is difficult to compare
      and contrast the results of reported series in the literature due to different
      definitions of AF; freedom from and recurrence of it. Furthermore, in most series
      it is difficult to distinguish results of surgery for lone AF and AF associated
      with valvular heart disease and coronary artery disease.

PMID- 16798261
TI  - Radiofrequency ablation of lung malignancies.
AB  - Radiofrequency ablation is a new technology that has been used successfully to
      treat hepatic tumors. Recently, an increasing number of reports have described
      the use of radiofrequency ablation for primary and metastatic lung tumors.
      Although such early experience appears promising, many questions regarding
      patient selection, radiofrequency ablation technique, effectiveness of ablation
      on lung tumors, radiographic follow-up, and survival remain unanswered. This
      article addresses these issues and provides the thoracic surgeon with a current
      review of the application of radiofrequency ablation to lung tumors.

PMID- 16798262
TI  - Cardiac papillary fibroelastoma.

PMID- 16798263
TI  - Deep sternal wound infection after cardiac surgery.

PMID- 16798264
TI  - Porcelain aorta: therapeutical options for aortic valve replacement and
      concomitant coronary artery bypass grafting.

PMID- 16798265
TI  - Coronary reimplantation after neoaortic reconstruction in arterial switch
      operation.

PMID- 16798267
TI  - Intrathoracic manifestation of cervical anastomotic leaks.

PMID- 16798269
TI  - What is a spontaneous hemothorax?

PMID- 16798271
TI  - Special issue: the intersection of stem/progenitor cell biology and hypoxic
      ischemic cerebral injury/stroke.

PMID- 16798272
TI  - PCOS (polycystic ovary syndrome): a multifaceted disease from adolescence to
      elderly. Proceedings of the second Special Scientific Meeting of the Androgen
      Excess Society. September 30-October 1, 2005. Ravello, Italy.

PMID- 16798273
TI  - Gonadotropin dysfunction in women with polycystic ovary syndrome.
AB  - Gonadotropin abnormalities are common in women with polycystic ovary syndrome.
      Interpretation of LH values depends on body weight, time of last ovulation, assay
      used, and the precision of the normative data against which a value is compared.

PMID- 16798274
TI  - Insulin resistance in women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is associated with insulin resistance. There are
      also defects in pancreatic beta-cell function in affected women. These
      abnormalities are heritable. There are post-binding defects in insulin receptor
      signaling, with selective resistance to insulin's metabolic actions and
      constitutively activated mitogenic signaling in skeletal muscle. Intrinsic and
      environmental abnormalities interact to produce peripheral insulin resistance in
      PCOS. A susceptibility gene region for PCOS is located on chromosome 19p13.2. The
      susceptibility allele is also associated with a metabolic phenotype.

PMID- 16798275
TI  - Candidate genes in women with polycystic ovary syndrome.
AB  - There is plentiful evidence that genetic factors have an important part to play
      in the etiology of polycystic ovary syndrome. As yet, however, none of the
      potential candidate loci have withstood the scrutiny of large case-control
      studies, although studies of a locus close to the insulin receptor gene on
      chromosome 19p are emerging as promising.

PMID- 16798276
TI  - Type 2 diabetes and polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) have multiple factors that contribute
      to increased diabetes risk, including: insulin resistance, beta-cell dysfunction,
      obesity, especially centripetal obesity, family history of type 2 diabetes, and
      personal history of gestational diabetes. Additionally there is some evidence to
      suggest that polycystic ovaries and chronic anovulation per se are risk factors.
      Identifying glucose intolerance and treating it are important aspects of the care
      for women with PCOS.

PMID- 16798277
TI  - Metabolic syndrome in women with polycystic ovary syndrome.
AB  - The prevalence of the metabolic syndrome in polycystic ovary syndrome (PCOS) is
      high across all age groups. Dyslipidemia, particularly a decreased high-density
      lipoprotein cholesterol level, also is common in women with PCOS.

PMID- 16798278
TI  - Nonclassic 21-hydroxylase deficiency.
AB  - Nonclassic 21-hydroxylase deficiency is a frequent autosomal recessive disorder
      which causes decreased fertility and is easily treated. It occurs with the
      highest frequency of any other autosomal recessive disorder in humans.

PMID- 16798279
TI  - Cardiovascular risk in women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is not only a reproductive problem but a
      complex, endocrine, multifaceted disease with several health complications.
      Cardiovascular abnormalities represent important long-term sequelae of PCOS.

PMID- 16798280
TI  - Choice of treatment for women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome presents with many different symptoms and signs, for
      which different therapies are indicated. However, for the majority of women, the
      metabolic disorder requires diligence in management, regardless of the presenting
      complaint.

PMID- 16798281
TI  - Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in
      nonobese adolescents and women.
AB  - Hyperinsulinemic hyperandrogenism is the core of polycystic ovary syndrome
      (PCOS), and, accordingly, low-dose flutamide-metformin proved so far to be a most
      effective approach to normalize the broad spectrum of PCOS anomalies in nonobese
      adolescents and young women. For safety reasons, it is wise to combine flutamide
      metformin with a contraceptive, for example, an oral or transdermal
      estroprogestagen.

PMID- 16798282
TI  - Ovulation induction in women with polycystic ovary syndrome.
AB  - To date, clomiphene citrate (CC) remains the first therapeutical step for
      inducing ovulation in anovulatory PCOS patients. Metformin alone or combined with
      CC is a valid second step approach, whereas the laparoscopic ovarian diathermy
      can be useful only in selected cases.

PMID- 16798283
TI  - Insulin-sensitizing agents in women with polycystic ovary syndrome.
AB  - Improvement of insulin resistance and, consequently, hyperinsulinemia is one of
      the main procedures for treating the polycystic ovary syndrome. The improvement
      of insulin resistance and the decrease in insulin concentration can be achieved
      in different ways: (1) by lifestyle modifications; (2) by using insulin
      sensitizing agents; and (3) by using antiandrogens.

PMID- 16798284
TI  - Nonclassic adrenal hyperplasia.
AB  - Among 297 women with nonclassic adrenal hyperplasia (NCAH), premature pubarche
      was the most common complaint in girls (87%), and the frequency of hirsutism
      increased progressively with age from adolescence (50%) to adulthood (70%). The
      frequency of spontaneous miscarriages was high in NCAH patients (20%), but it
      decreased significantly after treatment.

PMID- 16798285
TI  - Use of antiandrogens as therapy for women with polycystic ovary syndrome.
AB  - Because androgen excess plays a fundamental role in symptoms and, it is likely,
      in pathogenesis of polycystic ovary syndrome, attenuation of hyperandrogenism
      appears to be of paramount importance in the therapy of this condition.
      Consistently, drugs inhibiting androgen receptor binding not only are an
      effective tool in hirsutism treatment but also show favorable effects on body
      composition and metabolic features of these women.

PMID- 16798286
TI  - Prenatal growth restraint followed by catch-up of weight: a hyperinsulinemic
      pathway to polycystic ovary syndrome.
AB  - One of the pathways to polycystic ovary syndrome (PCOS) starts with an early-life
      sequence of prenatal growth restraint followed by catch-up of weight during
      infancy. This sequence results by mid-childhood in a pre-PCOS state including
      hyperinsulinemia, a low-grade proinflammatory state, an amplified adrenarche
      (with or without precocious pubarche), and an adipose body composition even in
      the absence of obesity. This variant of pre-PCOS and PCOS responds well to
      intervention with metformin.

PMID- 16798287
TI  - Clinical expression of polycystic ovary syndrome in adolescent girls.
AB  - Polycystic ovary syndrome (PCOS) is one of the major causes of adolescent
      hyperandrogenism and menstrual disorders. Because there is no universal
      definition for adolescent PCOS, we recommend four out of five criteria: clinical
      and biologic evidence of hyperandrogenism, hyperinsulinism, oligo-/amenorrhea,
      and polycystic ovaries on ultrasonography.

PMID- 16798288
TI  - Diagnosis, phenotype, and prevalence of polycystic ovary syndrome.
AB  - New diagnostic criteria for polycystic ovary syndrome (PCOS) suggested three main
      phenotypes: classic (hyperandrogenism and anovulation), ovulatory, and
      normoandrogenic. However, it is unclear whether the normoandrogenic phenotype
      actually represents PCOS. Overall, 6% to 8% of reproductive-aged women suffer
      from PCOS, making this disorder one of the most common endocrine abnormalities.

PMID- 16798289
TI  - Ovarian enzyme activities in women with polycystic ovary syndrome.
AB  - Studies using primary ovarian tissue and cultured human theca and granulosa cells
      have shown that steroidogenic enzyme activities are up-regulated in theca cells
      in polycystic ovary syndrome (PCOS). Although granulosa cells in arrested
      follicles in PCOS fail to express significant amounts of aromatase, there is an
      overexpression of 5alpha-reductase activity and premature expression of
      cholesterol side-chain cleavage cytochrome P450.

PMID- 16798290
TI  - Chest wall reconstruction with perforator flaps after wide full-thickness
      resection.

PMID- 16798291
TI  - Slide tracheoplasty in the presence of tracheal bronchus in an infant.

PMID- 16798293
TI  - Randomized controlled trials do not reflect reality: real-world analyses are
      critical for treatment guidelines!

PMID- 16798294
TI  - The "scientific investment" by cardiac surgery.

PMID- 16798295
TI  - Brain death leads to abnormal contractile properties of the human donor right
      ventricle.

PMID- 16798296
TI  - Risk factor identification and mortality prediction in cardiac surgery using
      artificial neural networks.
AB  - OBJECTIVE: The artificial neural network model is a nonlinear technology useful
      for complex pattern recognition problems. This study aimed to develop a method to
      select risk variables and predict mortality after cardiac surgery by using
      artificial neural networks. METHODS: Prospectively collected data from 18,362
      patients undergoing cardiac surgery at 128 European institutions in 1995 (the
      European System for Cardiac Operative Risk Evaluation database) were used. Models
      to predict the operative mortality were constructed using artificial neural
      networks. For calibration a sixfold cross-validation technique was used, and for
      testing a fourfold cross-testing was performed. Risk variables were ranked and
      minimized in number by calibrated artificial neural networks. Mortality
      prediction with 95% confidence limits for each patient was obtained by the
      bootstrap technique. The area under the receiver operating characteristics curve
      was used as a quantitative measure of the ability to distinguish between
      survivors and nonsurvivors. Subgroup analysis of surgical operation categories
      was performed. The results were compared with those from logistic European System
      for Cardiac Operative Risk Evaluation analysis. RESULTS: The operative mortality
      was 4.9%. Artificial neural networks selected 34 of the total 72 risk variables
      as relevant for mortality prediction. The receiver operating characteristics area
      for artificial neural networks (0.81) was larger than the logistic European
      System for Cardiac Operative Risk Evaluation model (0.79; P = .0001). For
      different surgical operation categories, there were no differences in the
      discriminatory power for the artificial neural networks (P = .15) but significant
      differences were found for the logistic European System for Cardiac Operative
      Risk Evaluation (P = .0072). CONCLUSIONS: Risk factors in a ranked order
      contributing to the mortality prediction were identified. A minimal set of risk
      variables achieving a superior mortality prediction was defined. The artificial
      neural network model is applicable independent of the cardiac surgical procedure.

PMID- 16798297
TI  - Risk-corrected impact of mechanical versus bioprosthetic valves on long-term
      mortality after aortic valve replacement.
AB  - OBJECTIVE: Choice of a mechanical or biologic valve in aortic valve replacement
      remains controversial and rotates around different complications with different
      time-related incidence rates. Because serious complications will always "spill
      over" into mortality, our aim was to perform a meta-analysis on overall mortality
      after aortic valve replacement from series with a maximum follow-up of at least
      10 years to determine the age- and risk factor-corrected impact of currently
      available mechanical versus stented bioprosthetic valves. METHODS: Following a
      formal study protocol, we performed a dedicated literature search of publications
      during 1989 to 2004 and included articles on adult aortic valve replacement with
      a mechanical or stented bioprosthetic valve if age, mortality statistics, and
      prevalences of well-known risk factors could be extracted. We used standard and
      robust regression analyses of the case series data with valve type as a fixed
      variable. RESULTS: We could include 32 articles with 15 mechanical and 23
      biologic valve series totaling 17,439 patients and 101,819 patient-years. The
      mechanical and biologic valve series differed in regard to mean age (58 vs 69
      years), mean follow-up (6.4 vs 5.3 years), coronary artery bypass grafting (16%
      vs 34%), endocarditis (7% vs 2%), and overall death rate (3.99 vs 6.33 %/patient
      year). Mean age of the valve series was directly related to death rate with no
      interaction with valve type. Death rate corrected for age, New York Heart
      Association classes III and IV, aortic regurgitation, and coronary artery bypass
      grafting left valve type with no effect. Included articles that abided by current
      guidelines and compared a mechanical and biologic valve found no differences in
      rates of thromboembolism. CONCLUSION: There was no difference in risk factor
      corrected overall death rate between mechanical or bioprosthetic aortic valves
      irrespective of age. Choice of prosthetic valve should therefore not be
      rigorously based on age alone. Risk of bioprosthetic valve degeneration in young
      and middle-aged patients and in the elderly and old with a long life expectancy
      would be an important factor because risk of stroke may primarily be related to
      patient factors.

PMID- 16798298
TI  - Effect of posterior pericardial drainage on the incidence of pericardial effusion
      after ascending aortic surgery.
AB  - OBJECTIVE: Pericardial effusion and cardiac tamponade after ascending aortic
      surgery are higher than anticipated after cardiac surgery. We evaluated a thin
      closed-suction drain system to prevent posterior pericardial effusion in patients
      undergoing ascending aortic surgery. METHODS: One hundred forty patients who
      underwent ascending aortic surgery were prospectively randomized into group A and
      group B. In group A (n = 70) we used a 32F drain placed anteriorly overlying the
      heart and a 16F thin drain placed retrocardially. In group B (n = 70) only a 32F
      drain placed anteriorly was used. In group A we removed the large drain on the
      first postoperative day and continued drainage with the thin drain until the
      drainage was less than 50 mL in a 24-hour period. In group B we removed the drain
      after the first postoperative day when the drainage was less than 50 mL in an 8
      hour period. Preoperative, perioperative, and postoperative parameters of the
      patients were compared. RESULTS: No significant posterior pericardial effusion
      and late cardiac tamponade developed in patients in group A. In group B 10
      (14.3%) patients experienced significant posterior pericardial effusion and 4
      (5.7%) patients experienced late cardiac tamponade; the incidence of significant
      pericardial effusion in group B was significantly higher (P = .001).
      Postoperative new-onset atrial fibrillation developed in 6 (10.4%) patients in
      group A and in 18 (32.7%) patients in group B (P = .03). CONCLUSIONS: We
      demonstrated that effective posterior drainage is important to prevent posterior
      pericardial effusion, and use of a thin drain placed retrocardially appears to be
      sufficient for these results.

PMID- 16798299
TI  - In vitro comparison of aortic valve movement after valve-preserving aortic
      replacement.
AB  - OBJECTIVE: In aortic valve regurgitation and aortic dilatation, preservation of
      the aortic valve is possible by means of root remodeling (Yacoub procedure) or
      valve reimplantation (David procedure). In vivo studies suggest that
      reimplantation might substantially influence aortic valve-motion characteristics.
      Evaluation of aortic valve movement in vivo, however, is technically limited and
      is difficult to standardize. We evaluated the aortic valve-motion pattern
      echocardiographically in vitro after reimplantation and remodeling. METHODS: By
      using aortic roots of house pigs (aortoventricular diameter, 22 mm) a Yacoub
      procedure (22-mm graft; group Y, n = 5) or a David I procedure (24-mm graft;
      group D, n = 5) was performed. Roots after supracommissural replacement (22-mm
      graft; group C, n = 5) served as control valves. In an electrohydraulic, computer
      controlled pulse duplicator the valves were tested at flows of 2, 4, 7, and 9
      L/min. Echocardiographically assessed parameters were rapid valve-opening
      velocity, slow valve-closing velocity, rapid valve-closing velocity, rapid valve
      opening time, rapid valve-closing time, ejection time, maximum valve opening,
      slow valve-closing displacement, and maximum flow velocity. RESULTS: Mean rapid
      valve-opening velocity and mean rapid valve-closing velocity at a cardiac output
      of 2 to 9 L/min were fastest in group D (rapid valve-opening velocity: 69 +/- 10
      cm/s [group D] vs 39 +/- 4 cm/s [group Y] vs 42 +/- 4 cm/s [group C], P = .0041;
      rapid valve-closing velocity: 22 +/- 2 cm/s [group D] vs 16 +/- 2 cm/s [group Y]
      vs 17 +/- 1 cm/s [group C], P = .0272), and slow valve-closing velocity was
      slowest in group D (0.2 +/- 0.1 cm/s [group D] vs 1.0 +/- 0.3 cm/s [group Y] vs
      0.6 +/- 0.1 cm/s [group C], P = .0063). With increasing cardiac output, the
      difference in rapid valve-opening velocity between the groups increased, the
      difference in slow valve-closing velocity remained unchanged, and the difference
      in rapid valve-closing velocity decreased. CONCLUSIONS: In this standardized
      experimental setting remodeling of the aortic valve provides significantly
      smoother valve movements. This might contribute to preservation of a better valve
      performance during long-term follow-up.

PMID- 16798300
TI  - Influence of sternal size and inadvertent paramedian sternotomy on stability of
      the closure site: a clinical and mechanical study.
AB  - BACKGROUND: The influence of sternal size and of inadvertent paramedian
      sternotomy on stability of the closure site is not well defined. METHODS: Data on
      171 consecutive patients undergoing cardiac surgery through a midline sternotomy
      were prospectively collected. Intraoperative measurements of sternal dimension
      included thickness and width at the manubrium, the third and fifth intercostal
      spaces; paramedian sternotomy was defined as width of one side of the sternum
      equaling 75% or more of the entire width, at any of the three levels. The chest
      was closed with simple peristernal steel wires and inspected to detect deep wound
      infection and/or instability for 3 postoperative months. The sternal factors and
      several patient/surgery-related factors were included in a multivariate analysis
      model to identify factors affecting stability. An electromechanical traction test
      was conducted on 6 rewired sternal models after midline or paramedian sternotomy
      and separation data were analyzed. RESULTS: Chest instability was detected in 12
      (7%) patients and wound infection in 2 (1.2%). Patient weight (P = .03),
      depressed left ventricular function (P = .04), sternum thickness (indexed to body
      weight, P = .03), and paramedian sternotomy (P = .0001) were risk factors of
      postoperative instability; paramedian sternotomy was the only independent
      predictor (P = .001). The electromechanical test showed more lateral displacement
      of the two rewired sternal halves after paramedian than midline sternotomy (P =
      .002); accordingly, load at fracture point was lower after paramedian sternotomy
      (220 +/- 20 N vs 545 +/- 25 N, P = 0.001). CONCLUSIONS: Inadvertent paramedian
      sternomoty strongly affects postoperative chest wound stability independently
      from sternal size, requiring prompt reinforcement of chest closure.

PMID- 16798301
TI  - Dynamic right ventricular outflow tract obstruction in cardiac surgery.
AB  - BACKGROUND: Right ventricular outflow tract obstruction can be a cause of
      hemodynamic instability but it has not been described in non-congenital cardiac
      surgery. METHODS: The prevalence of right ventricular outflow tract obstruction
      was retrospectively studied in 670 consecutive patients undergoing cardiac
      surgery. Significant right ventricular outflow tract obstruction was diagnosed if
      the right ventricular systolic to pulmonary artery peak gradient was more than 25
      mm Hg. The diagnosis was based on measurement of the right ventricular and
      pulmonary artery systolic pressure through the paceport and distal opening of the
      pulmonary artery catheter. To further validate the prevalence and the importance
      of right ventricular outflow tract obstruction, 130 patients were prospectively
      studied over a 12-month period. RESULTS: In the retrospective cohort, 6 patients
      (1%) undergoing various types of cardiac surgical procedures were found to have
      significant dynamic right ventricular outflow tract obstruction with a mean
      gradient of 31 +/- 4 mm Hg (26 to 35 mm Hg). In the prospective study significant
      dynamic right ventricular outflow tract obstruction was identified in 5 patients
      (4%) (average peak: 37 +/- 15 mm Hg; range: 27 to 60 mm Hg). The typical
      transesophageal echocardiography finding was end-systolic obliteration of the
      right ventricular outflow tract. In patients with significant dynamic right
      ventricular outflow tract obstruction, hemodynamic instability was present in
      10/11 patients (91%). CONCLUSIONS: Right ventricular outflow tract obstruction is
      easily diagnosed using the paceport of the pulmonary artery catheter and should
      be considered as a potential cause of hemodynamic instability especially when
      transesophageal echocardiography reveals systolic right ventricular cavity
      obliteration.

PMID- 16798302
TI  - Results of surgery for Ebstein anomaly: a multicenter study from the European
      Congenital Heart Surgeons Association.
AB  - OBJECTIVE: Since most centers' experience with Ebstein anomaly is limited, we
      sought to analyze the collective experience of participating institutions of the
      European Congenital Heart Surgeons Association with surgery for this rare
      malformation. METHODS: The records of all 150 patients (median age 6.4 years) who
      underwent surgery for Ebstein anomaly in the 13 participating Association centers
      between January 1992 and January 2005 were reviewed retrospectively. Patients
      with congenitally corrected transposition were excluded. RESULTS: Most patients
      (81%) had Ebstein disease type B or C and significant functional impairment (61%
      in New York Heart Association class III or IV) and 16% had prior operations.
      Surgical procedures (n = 179) included valve replacement (n = 60, 33.5%), valve
      repair (n = 49, 27.3%), 1(1/2) ventricle repair (n = 46, 25.6%), palliative shunt
      (n = 13, 7.26%), and other complex procedures (n = 11, 6.14%). There were 20
      hospital deaths (operative mortality 13.3%) after valve replacement in 5
      patients, valve repair in 3, 1(1/2) ventricle repair in 7, palliative procedures
      in 3, and miscellaneous procedures in 2. Younger age and palliative procedures
      were univariate risk factors for operative death, but only age was an independent
      predictor on multivariable analysis. CONCLUSIONS: Most patients coming to surgery
      presented in childhood and were significantly symptomatic. More than half
      underwent valve replacement or repair, but a considerable proportion had severe
      disease necessitating 1(1/2) ventricle repair or palliative procedures. Operative
      mortality did not differ significantly among repair, replacement, and 1(1/2)
      ventricle repair but was associated with palliative procedures for severe disease
      early in life, young age being the only independent predictor of operative death.

PMID- 16798303
TI  - Nitric oxide precursors and congenital heart surgery: a randomized controlled
      trial of oral citrulline.
AB  - OBJECTIVE: The study sought to determine whether citrulline supplementation, a
      precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma
      citrulline concentrations and decreasing the risk of postoperative pulmonary
      hypertension. STUDY DESIGN: Forty children, undergoing cardiopulmonary bypass and
      at risk for pulmonary hypertension, were randomized to receive 5 perioperative
      doses (1.9 g/m2 per dose) of either oral citrulline or placebo. Plasma citrulline
      and arginine concentrations were measured at 5 time points. Measurements of
      systemic blood pressure and presence of pulmonary hypertension were collected.
      RESULTS: Median citrulline concentrations were significantly higher in the
      citrulline group versus the placebo group immediately postoperatively (36
      micromol/L vs 26 micromol/L, P = .012) and at 12 hours postoperatively (37
      micromol/L vs 20 micromol/L, P = .015). Mean plasma arginine concentrations were
      significantly higher in the citrulline group versus the placebo group by 12 hours
      postoperatively (36 micromol/L vs 23 micromol/L, P = .037). Mean systemic blood
      pressure did not differ between groups (P = .53). Postoperative pulmonary
      hypertension developed in 9 patients, 6 of 20 (30%) in the placebo group and 3 of
      20 (15%) in the citrulline group (P = .451), all of whom had plasma citrulline
      concentrations less than age-specific norms. Postoperative pulmonary hypertension
      did not develop in patients who demonstrated plasma citrulline concentrations in
      excess of 37 mumol/L (P = .036). CONCLUSIONS: Oral citrulline supplementation
      safely increased plasma citrulline and arginine concentrations compared with
      placebo after cardiopulmonary bypass. Postoperative pulmonary hypertension did
      not occur in children with naturally elevated citrulline levels or elevations
      through supplementation. Oral citrulline supplementation may be effective in
      reducing postoperative pulmonary hypertension.

PMID- 16798304
TI  - Evaluation of downsized homograft conduits for right ventricle-to-pulmonary
      artery reconstruction.
AB  - OBJECTIVE: Although homograft conduits are frequently used to establish right
      ventricle-to-pulmonary artery continuity, the limited availability of small-size
      homografts is a significant constraint in pediatric cardiac surgery. We compared
      the performance of standard homograft conduits with that of surgically reduced
      bicuspid homograft conduits in patients undergoing repair of truncus arteriosus.
      METHODS: Forty infants undergoing complete repair of truncus arteriosus with
      either standard homografts (n = 26) or reduced-size bicuspid homografts (n = 14)
      were evaluated. RESULTS: The median downsized conduit diameter (13 mm) was
      similar to the standard homograft diameter (12 mm, P = .52). There were 6 early
      deaths and 5 late deaths, representing an overall 30-day mortality of 15% and a 5
      year mortality of 25%. No deaths were directly related to homograft dysfunction.
      Four (29%) downsized conduits and 8 (31%) standard conduits required replacement
      at a median interval of 18.5 months and 42.4 months, respectively. Catheter-based
      interventions were required in 5 (36%) patients in the downsized group and in 3
      (12%) patients in the standard group. There was no difference in freedom from
      surgical or catheter-based reintervention between the 2 groups (P = .42). Freedom
      from conduit failure (severe conduit stenosis, moderate or greater regurgitation)
      was 55.9% and 17.2% at 3 years in the downsized and standard groups,
      respectively. CONCLUSION: The surgically downsized homograft is an excellent
      option when an appropriate-sized homograft is not available and might prevent
      morbidity associated with the use of an oversized conduit.

PMID- 16798305
TI  - Myocardial protection using an omega-3 fatty acid infusion: quantification and
      mechanism of action.
AB  - OBJECTIVES: Omega-3 fatty acids exhibit anti-inflammatory, antithrombotic, and
      antiarrhythmic properties. We investigated the extent and underlying mechanism of
      protection conferred by a pre-emptive omega-3 infusion in a model of regional
      cardiac ischemia-reperfusion injury. METHODS: New-Zealand White rabbits received
      either the omega-3 infusion or a control infusion of 0.9% saline (n = 14 in each
      group). The large marginal branch of the left coronary artery was occluded for 30
      minutes, cardiac function was assessed during 3 hours of reperfusion, and infarct
      size was measured. Pretreatment-induced alterations in myocardial membrane fatty
      acid composition and intramyocardial heat shock protein 72 were additionally
      assessed (n = 5 in each group). Serum markers of myocardial membrane oxidative
      stress, malonaldehyde and 8-isoprostane, were also determined. Results are
      expressed as means +/- standard error of the mean and significance was tested
      with analysis of variance. RESULTS: Pretreatment increased myocardial membrane
      omega-3 fatty acid content 5-fold, from 0.94% +/- 0.07% in controls to 5.38% +/-
      0.44% in the omega-3 group (P < .01), and it produced a 225% elevation of levels
      of heat shock protein 72 (P = .019) before ischemia-reperfusion. This was
      associated with a 40% reduction in infarct size (P < .01). Whereas the
      reperfusion-induced rise in malonaldehyde levels was higher with omega-3
      pretreatment, 10.2 +/-1.5 micromol/L versus 6.1 +/- 0.7 micromol/L in controls (P
      = .04), 8-isoprostanes showed a 9-fold reduction, 679 +/- 190 pg/mL in controls
      vs 74 +/- 45 pg/mL in the omega-3 group (P = .0077). CONCLUSIONS: A pre-emptive
      omega-3 infusion significantly reduces infarct size through the dual mechanisms
      of upregulation of heat shock protein 72, a key preconditioning protein, and a
      dramatic increase in the omega-3 content of myocardial membranes, which appears
      to facilitate a shift in oxidant ischemia-reperfusion injury. Further study to
      optimally shorten the pretreatment regimen for this potentially acceptable
      infusion will now be pursued.

PMID- 16798306
TI  - Intermittent pressure augmentation during retrograde cerebral perfusion under
      moderate hypothermia provides adequate neuroprotection: an experimental study.
AB  - OBJECTIVE: For cerebral protection during aortic surgery, we introduced a novel
      retrograde cerebral perfusion method with intermittent pressure augmentation. We
      then assessed whether this novel method provides benefits similar to those
      provided by antegrade selective cerebral perfusion. METHODS: Eighteen dogs were
      randomly divided into 3 groups: the RCP-INT group, intermittent-retrograde
      cerebral perfusion at 15 mm Hg with intermittent pressure augmentation to 45 mm
      Hg (n = 6); the ASCP group, antegrade selective cerebral perfusion at a flow rate
      of 10 mL x kg(-1) x min(-1) (n = 6); and the sham group, no circulatory arrest (n
      = 6). Cooling (26 degrees C) with cardiopulmonary bypass and 60 minutes of
      circulatory arrest were performed in the RCP-INT and ASCP groups. The levels of
      tau protein in the cerebrospinal fluid and the diameters of the retinal vessels
      were measured. The neurologic deficit scores and the histopathologic damage
      scores of the brains were determined. RESULTS: The total postoperative tau
      protein levels (calculated as the area under the curve) did not differ
      significantly between the RCP-INT and ASCP groups (203 +/- 87 pg x mL(-1) x h vs
      154 +/- 69 pg x mL(-1) x h, P = .95). The retinal vessels were effectively
      dilated at an augmented pressure of 45 mm Hg in the RCP-INT group. The total
      neurologic deficit score (0 = normal, 500 = brain death) and histopathologic
      damage score (0 = normal, 40 = worst) were not significantly different between
      the RCP-INT and ASCP groups (neurologic deficit score: 75 +/- 21 vs 70 +/- 21, P
      = .98; histopathologic damage score: 13.5 +/- 1.5 vs 14.2 +/- 1.3, P = .84).
      CONCLUSIONS: Intermittent augmented pressure dilated the cerebral vessels,
      allowing adequate blood supply without injuring the brain. This retrograde
      cerebral perfusion method provides adequate neuroprotection during moderate
      hypothermia.

PMID- 16798308
TI  - Bronchoscopic treatment of postpneumonectomy bronchopleural fistula with a
      collagen screw plug.
AB  - OBJECTIVE: Bronchopleural fistula is a critical complication that may occur after
      pulmonary resection. Early closure of the fistula is required to prevent thoracic
      empyema or aspiration pneumonia. We have designed a novel procedure for
      bronchoscopic occlusion of the fistula with a collagen screw plug and assessed
      its feasibility in an experimental animal model. METHODS: Adult beagle dogs
      underwent right or left pneumonectomy, and the bronchial stump was closed with
      the Sweet method. A silicone bar (2 mm in diameter) was then placed in the middle
      of the bronchial stump. Seven days after the operation, the silicone bar was
      removed bronchoscopically, and fistula formation was confirmed. A screw-shaped 2%
      collagen screw plug (20 mm long and 3 mm in diameter) was mounted at the end of a
      modified endoscopic cannula and then inserted into the fistula. Autologous
      platelet-rich plasma was then soaked onto the inserted plug. RESULTS: Nine of 10
      beagle dogs with bronchopleural fistula were treated successfully by plug
      occlusion. One dog died of pneumothorax caused by dislocation of the plug.
      Pathologic examination revealed that the collagen sponge had been replaced by
      fibrous tissue and that the fistula was covered with normal epithelium. Although
      soaking with platelet-rich plasma made the plug airtight immediately, the use of
      platelet-rich plasma seemed to make no distinct difference with respect to the
      treatment result or pathologic findings. CONCLUSION: Bronchoscopic occlusion with
      a collagen screw plug is a promising option for treatment of small bronchopleural
      fistulas after pulmonary surgery.

PMID- 16798307
TI  - Factors influencing calcification of cardiac bioprostheses in adolescent sheep.
AB  - OBJECTIVE: We determined the possible effects of age, antimineralization
      treatments, circulatory implant conditions, prosthesis design, and valve-related
      structural aspects on valve calcification in adolescent sheep. METHODS: Calcium
      content was measured by means of atomic absorption spectrometry in bioprostheses
      implanted in 120 sheep (age <1 year) for a period of 3 or 6 months. RESULTS:
      Bioprostheses calcified significantly in adolescent sheep, but the extent of
      calcification was multifactorial. Multivariate analysis of the calcium content
      reveals that age, mitral or pulmonary implant position, prosthesis design
      (stented or stentless), structure (porcine or pericardial, wall portion or cusp),
      and antimineralization treatment are independent factors influencing
      calcification; implant duration beyond 3 months was not. In juvenile sheep (age 5
      months) the wall portion, as well as the cusps of the prosthesis, calcified
      significantly more than in adolescent sheep (age 11 months). Irrespective of age,
      the cusps of valves implanted in the mitral position calcified more than those in
      the pulmonary position. The wall portion of stentless valves calcified more than
      that of stented valves, and pericardial valves calcified less than porcine
      valves. The surfactant (Tween 80, No-React, and alpha-amino-oleic acid) and
      alcohol (ethanol and octanediol) treatment significantly reduced cusp
      calcification; sodium dodecylsulfate did not. None of the anticalcification
      treatments was able to prevent wall calcification in stentless porcine valves.
      CONCLUSION: These findings suggest that tissue valve calcification is determined
      by many independent factors, which can be identified by using adolescent sheep as
      a preclinical in vivo model.

PMID- 16798309
TI  - A prospective, randomized, controlled trial of the effectiveness of BioGlue in
      treating alveolar air leaks.
AB  - OBJECTIVE: The use of tissue glues has been advocated to reduce post-thoracotomy
      alveolar air leaks, but outcomes have been inconclusive. The aim of this study
      was to determine the effectiveness of BioGlue (CryoLife Europa Ltd, Hampshire,
      United Kingdom) in eliminating post-thoracotomy alveolar air leaks. METHODS: A
      prospective, randomized, single-blind, controlled trial was conducted in which
      patients were stratified according to the severity of post-thoracotomy air leak
      that could not be controlled by conventional surgical techniques. They were
      allocated to a control arm (surgical treatment only) or an interventional arm
      (surgical treatment and BioGlue). Duration of air leak, intercostal drainage, and
      hospital stay comprised primary study end points. RESULTS: From December 2002 to
      January 2005, 52 patients were randomized, 29 (56%) of whom were men. The mean
      age was 59 +/- 15 years, and other characteristics were comparable in both
      groups. Indications for surgery were malignancy in 46 patients (88%), carcinoid
      tumor in 2 patients (4%), and infective disease in 4 patients (8%). Patients in
      the BioGlue arm had shorter median duration of air leaks, 1 (0-2) versus 4 (2-6)
      days (P < .001); intercostal chest drainage, 4 (3-4) versus 5 (4-6) days (P =
      .012); and hospital stay, 6 (5-7) versus 7 (7-10) days (P = .004), compared with
      controls. No major complications were encountered using BioGlue. CONCLUSIONS:
      This study demonstrates clear benefit from BioGlue in the treatment of alveolar
      air leaks through reduction of air leak duration, chest drainage time, and
      hospital stay. Systematic use of BioGlue may be warranted in adult thoracic
      surgical procedures (except pneumonectomy and decortication) when an air leak
      remains after all other steps to control it have failed.

PMID- 16798310
TI  - Long-term outcome of bronchoscopically resected endobronchial typical carcinoid
      tumors.
AB  - BACKGROUND: Typical pulmonary carcinoid tumors represent less than 1% of lung
      tumors. In a subgroup of patients with this abnormality, the tumor is entirely
      endobronchial. We assessed the long-term outcome of such cases in which the
      patient was managed with endobronchial resection only. METHODS: Patients who
      underwent bronchoscopic resection for a typical carcinoid tumor were identified
      through case records and histology reports. Data were collected retrospectively,
      but follow-up was on a prospective basis through the outpatient clinic. RESULTS:
      Between 1978 and 2004, 28 patients underwent bronchoscopic resection of
      endobronchial carcinoid tumors. The mean age was 49 years (standard deviation, 19
      years; age range, 11-82 years), with 46% (13/28) of the patients being male. The
      tumor arose from the left bronchial tree in 61% (17/28), with the most common
      site being the left lower lobe bronchus (8/28). On average, patients required 5
      bronchoscopic resections to achieve complete resection. The median follow-up was
      8.8 years (interquartile range, 4.5-13.7 years). At 1 and 10 years, 100% and 94%
      of patients were disease free, respectively. The 1- and 10-year survivals were
      89% (interquartile range, 84%-93%) and 84% (interquartile range, 77%-91%),
      respectively. CONCLUSION: In a selected group of patients, proximal polypoid
      typical bronchial carcinoid tumors can be treated endobronchially with good
      outcome.

PMID- 16798311
TI  - Brain death leads to abnormal contractile properties of the human donor right
      ventricle.
AB  - OBJECTIVES: Experimental and clinical data suggest that brain death predominantly
      affects the right ventricle. We aimed to investigate right ventricle function
      after brain death and during clinical transplantation with load-independent
      methods. METHODS: Patients with and without brain death were enrolled. A total of
      33 consecutive heart donors (5 live, "domino" donors) and 10 patients undergoing
      coronary surgery (coronary artery bypass graft controls) were studied with
      pressure-volume loops in the right ventricle. Contractile reserve was measured
      with dopamine stimulation. RESULTS: Brain-dead donors had a higher mean cardiac
      index than coronary artery bypass graft controls (3.3 vs 2.8 L/min/m2), but
      impaired load-independent indices. Despite increased right ventricle stroke
      volume, the ejection fraction and slope of the end-systolic pressure-volume
      relationship were significantly reduced in brain-dead donors compared with
      controls. Diastolic abnormalities were also manifest as increased end-diastolic
      volume index and prolonged Tau (P < .05). Dopamine improved cardiac output, but
      without influencing end-systolic pressure-volume relationship, or Tau, and at the
      expense of further increased right ventricle end-diastolic volume. Before
      explantation, a significantly higher diastolic volume was also seen in hearts
      that developed postoperative dysfunction compared with organs without this
      complication (114.4 vs 77.2 mL/m2, P = .02). CONCLUSIONS: Brain death leads to
      right ventricle dysfunction, which may go undetected with conventional
      techniques. Right ventricle dilatation could represent an early marker of
      failure. Refinement of selection criteria to include load-independent indices of
      performance may be desirable to help expand the donor pool.

PMID- 16798312
TI  - Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction
      evolution toward heart failure.
AB  - OBJECTIVE(S): Even though the mechanism is not clearly understood, direct
      intramyocardial cell transplantation has demonstrated potential to treat patients
      with severe heart failure. We previously reported on the bioengineering of
      myoblast-based constructs. We investigate here the functional outcome of
      infarcted hearts treated by implantation of myoblast-seeded scaffolds. METHODS:
      Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection
      fraction (48.3% +/- 1.1%) were randomized to (1) implantation of myoblast-seeded
      polyurethane patches at the site of infarction (PU-MyoB, n = 11), (2)
      implantation of nonseeded polyurethane patches (PU, n = 11), (3) sham operation
      (Sham, n = 12), and (4) direct intramyocardial myoblast injection (MyoB, n = 11).
      Four weeks later, the functional assessment by echocardiography was repeated, and
      we additionally performed left ventricular catheterization plus histologic
      studies. RESULTS: The ejection fraction significantly decreased in the PU (39.1%
      +/- 2.3%; P = .02) and Sham (39.9% +/- 3.5%; P = .04) groups, whereas it remained
      stable in the PU-MyoB (48.4% +/- 3.1%) and MyoB (47.9% +/- 3.0%) groups during
      the observation time. Similarly, left ventricular contractility was significantly
      higher in groups PU-MyoB (4960 +/- 266 mm Hg/s) and MyoB (4748 +/- 304 mm Hg/s)
      than in groups PU (3909 +/- 248 mm Hg/s, P = .01) and Sham (4028 +/- 199 mm Hg/s,
      P = .01). Immunohistology identified a high density of myoblasts within the
      seeded scaffolds without any migration toward the host cardiac tissue and no
      evidence of cardiac cell differentiation. CONCLUSIONS: Myoblast-seeded
      polyurethane scaffolds prevent post-myocardial infarction progression toward
      heart failure as efficiently as direct intramyocardial injection. The
      immunohistologic analysis suggests that an indirect mechanism, potentially a
      paracrine effect, may be assumed.

PMID- 16798313
TI  - Inhaled nitric oxide reduces ischemia-reperfusion injury in rat lungs from non
      heart-beating donors.
AB  - OBJECTIVE: If lungs could be retrieved from non-heart-beating donors, the
      critical shortage of lungs for transplantation could be alleviated. However,
      lungs subjected to warm ischemia develop edema when reperfused. We hypothesized
      that ventilation of rat lungs from non-heart-beating donors with nitric oxide
      during the period of warm ischemia alone, with reperfusion, or both might reduce
      ischemia-reperfusion injury. METHODS: An isolated perfused rat lung model
      measured the filtration coefficient and accumulation of lung water by the wet/dry
      weight ratio. Donor rats were euthanized, and then lungs were retrieved
      immediately after death or 2 or 3 hours postmortem. Lungs retrieved postmortem
      were either not ventilated or ventilated with 100% oxygen alone or 40 ppm nitric
      oxide in oxygen. In the circuit, lungs were ventilated with alveolar gas with or
      without 40 ppm nitric oxide. RESULTS: Nitric oxide administration to the non
      heart-beating donor or in the perfusion circuit reduced filtration coefficient
      and wet/dry weight ratio. Lungs retrieved 2 hours postmortem ventilated with
      nitric oxide or treated with nitric oxide on reperfusion had filtration
      coefficients and wet/dry weight ratios similar to those of lungs retrieved
      immediately after death. Nitric oxide was most beneficial when administered both
      during warm ischemia and at reperfusion in lungs retrieved 3 hours postmortem.
      Nitric oxide administration in the circuit was associated with increased lung
      levels of lung cyclic guanosine monophosphate, determined by enzyme-linked
      immunosorbent assay. CONCLUSIONS: Administration of nitric oxide to non-heart
      beating donors during warm ischemia and with reperfusion might facilitate
      transplantation of lungs from non-heart-beating donors by reducing ischemia
      reperfusion injury and capillary leak.

PMID- 16798315
TI  - Endoscopic redo tricuspid valve replacement in complete situs inversus.

PMID- 16798314
TI  - Definitions of primary graft dysfunction after lung transplantation: differences
      between bilateral and single lung transplantation.
AB  - OBJECTIVE: The primary graft dysfunction definition has been applied to both
      bilateral lung transplantation and single lung transplantation. However, the
      differences between bilateral and single lung transplantation in terms of primary
      graft dysfunction remain unknown. This study aims to investigate the features and
      utility of the new primary graft dysfunction grading system by comparing early
      outcomes from bilateral and single lung transplantation. METHODS: The primary
      graft dysfunction grade of 228 consecutive lung transplants (149 bilateral and 79
      single lung transplants) at multiple postoperative time points was analyzed.
      Subgroup analysis with chronic obstructive pulmonary disease was performed to
      further validate the difference between bilateral lung transplantation and single
      lung transplantation. RESULTS: The percentage of grade 3 primary graft
      dysfunction in bilateral and single lung transplants was 32% and 37% at 0 hours
      (T0), 9% and 33% at 12 hours (T12), 7% and 26% at 24 hours (T24), and 9% and 18%
      at 72 hours (T72), respectively. The prevalence of the grade 3 primary graft
      dysfunction (T24) was significantly different between those undergoing bilateral
      lung transplantation and those undergoing single lung transplantation (P = .02).
      The primary graft dysfunction grade (T0) significantly correlated with the
      duration of intubation in both bilateral (r = 0.35, P < .0001) and single (r =
      0.42, P = .001) lung transplantation and length of intensive care unit stay in
      both bilateral (r = 0.31, P = .0002) and single (r = 0.33, P = .006) lung
      transplantation. These differences were validated by the subgroup analysis.
      CONCLUSIONS: The prevalence of primary graft dysfunction grade is different
      between bilateral and single lung transplantation and varies with time. Although
      the primary graft dysfunction grade correlated with the early posttransplantation
      outcomes, for the purposes of description and further studies, primary graft
      dysfunction in bilateral and single lung transplantation should be considered
      separately.

PMID- 16798317
TI  - Left atrial dissection: a multifaceted complication.

PMID- 16798316
TI  - Cardiac inflammatory myofibroblastic tumor as a rare cause of aortic
      regurgitation: a case report.

PMID- 16798318
TI  - Mild hypothermia (32 degrees C) and antegrade cerebral perfusion in aortic arch
      operations.

PMID- 16798319
TI  - Unusual thrombus formation in the aorta after apicoaortic conduit for severe
      aortic stenosis.

PMID- 16798320
TI  - Open repair of a new aneurysm of the thoracoabdominal aorta after endovascular
      stent placement.

PMID- 16798321
TI  - Right atrial mass: thrombus, myxoma, or cardiac papillary fibroelastoma?

PMID- 16798323
TI  - Newly designed extracardiac direct total cavopulmonary connection with merged
      connection and mixing route.

PMID- 16798322
TI  - Accessory mitral valve causing left ventricular outflow tract obstruction and
      mitral insufficiency.

PMID- 16798324
TI  - Adult congenital heart disease: cor triatriatum dextrum.

PMID- 16798325
TI  - Novel use of a retroaortic innominate vein in cavopulmonary anastomosis.

PMID- 16798326
TI  - A closed biatrial procedure using bipolar radiofrequency ablation.

PMID- 16798327
TI  - Robotic minimally invasive cell transplantation for heart failure.

PMID- 16798328
TI  - Percutaneous closure of a ventricular septal defect after surgical treatment of
      hypertrophic cardiomyopathy.

PMID- 16798329
TI  - Endothelial and smooth muscle cell populations in a decellularized cryopreserved
      aortic homograft (SynerGraft) 2 years after implantation.

PMID- 16798330
TI  - Off-pump connection of the pulmonary veins with bipolar radiofrequency: toward a
      complete epicardial ablation.

PMID- 16798331
TI  - Slide cricotracheoplasty in an infant.

PMID- 16798332
TI  - Slide tracheobronchoplasty in an infant.

PMID- 16798333
TI  - Methicillin-resistant Staphylococcus aureus infection causing Pancoast syndrome.

PMID- 16798335
TI  - Dual-layer sandwich mesh repair in the treatment of major diaphragmatic
      eventration in an adult.

PMID- 16798334
TI  - Pulmonary sequestration at the posterior mediastinum in a neonate.

PMID- 16798336
TI  - An unusual case of lateral pulmonary hernia.

PMID- 16798337
TI  - Carcinoma showing thymus-like elements invading the trachea.

PMID- 16798338
TI  - A new technique for prosthetic reconstruction of the superior vena cava.

PMID- 16798339
TI  - Atriocaval laceration presenting as delayed pericardial tamponade.

PMID- 16798340
TI  - Thymectomy for paraneoplastic stiff-person syndrome associated with invasive
      thymoma.

PMID- 16798341
TI  - Postoperative pulmonary embolism detected with multislice computed tomography in
      lung surgery for cancer.

PMID- 16798342
TI  - Pulmonary metastases of adult Wilms' tumor 17 years after the primary site.

PMID- 16798343
TI  - Tracheal glomus tumor.

PMID- 16798344
TI  - Pathologic features of cryopreserved aortic allograft implanted in the active
      infection.

PMID- 16798345
TI  - Extensive dissection of the pulmonary artery treated with combined heart-lung
      transplantation.

PMID- 16798346
TI  - Stroke prevention by means of epicardial occlusion of the left atrial appendage.

PMID- 16798347
TI  - Is it really the number of clamps that is responsible for worse postbypass
      neurological outcomes?

PMID- 16798349
TI  - Redo coronary bypass grafting: role of arterial grafts and time interval.

PMID- 16798352
TI  - More pumps--more questions.

PMID- 16798353
TI  - Is off-pump therapy really the right choice in urgent coronary grafting?

PMID- 16798355
TI  - Atrial ablation and esophageal injury: comments on an experimental study.

PMID- 16798357
TI  - Positron emission tomographic scanning in the diagnosis and staging of non-small
      cell lung cancer 2 cm in size or less.

PMID- 16798358
TI  - Use of autologous adult stem cell for treatment of congestive heart failure.

PMID- 16798359
TI  - Pulmonary lobectomy for cancer in patients with chronic obstructive pulmonary
      disease.

PMID- 16798361
TI  - Dor fundoplication after myotomy for achalasia: useful, unnecessary, or harmful?

PMID- 16798364
TI  - The USA's emergency-medicine crisis.

PMID- 16798365
TI  - Rolling out HPV vaccines worldwide.

PMID- 16798366
TI  - Lessons from kuru.

PMID- 16798367
TI  - Q waves to guide treatment of myocardial infarction.

PMID- 16798368
TI  - Artemisinin combination therapies.

PMID- 16798369
TI  - Climate change and health.

PMID- 16798370
TI  - Reforming drug-control policy for palliative care in Romania.

PMID- 16798371
TI  - Depressed patients and treatment adherence.

PMID- 16798372
TI  - Sexual and reproductive health rights in Africa.

PMID- 16798373
TI  - Recommendations for alcohol-related liver disease.

PMID- 16798374
TI  - Cuttings.

PMID- 16798377
TI  - Family observation of antituberculosis treatment.

PMID- 16798378
TI  - Family observation of antituberculosis treatment.

PMID- 16798379
TI  - Folic acid: a public-health challenge.

PMID- 16798380
TI  - Are systematic reviews more cost-effective than randomised trials?

PMID- 16798381
TI  - Folic acid: a public-health challenge.

PMID- 16798382
TI  - Folic acid: a public-health challenge.

PMID- 16798383
TI  - Finding a vaccine for human papillomavirus.

PMID- 16798384
TI  - Systematic reviews: when is an update an update?

PMID- 16798385
TI  - Aspirin resistance.

PMID- 16798386
TI  - Surgical treatment for blushing.

PMID- 16798387
TI  - Ethical flaws in Romania's health reform.

PMID- 16798389
TI  - Initial Q waves accompanying ST-segment elevation at presentation of acute
      myocardial infarction and 30-day mortality in patients given streptokinase
      therapy: an analysis from HERO-2.
AB  - BACKGROUND: The presence of pathological Q waves in the infarct leads on the
      surface electrocardiogram in an ST-elevation acute myocardial infarction
      indicates myocardial necrosis. Clinically it might be difficult to ascertain the
      onset of acute myocardial infarction. Our aim was to assess whether the presence
      or absence of Q waves at presentation could be used as an indicator of the
      duration of acute myocardial infarction and predict mortality. METHODS: 15,222
      patients with ST-elevation acute myocardial infarction and normal
      intraventricular conduction were randomly assigned streptokinase and aspirin plus
      bivalirudin or unfractionated heparin in the HERO-2 trial; randomisation did not
      alter 30-day mortality. 10,244 patients (67%) had Q waves in the infarct
      territory at the time of randomisation, and 4978 (33%) did not. The primary
      endpoint was 30-day mortality. FINDINGS: There were more deaths at 30 days in
      patients with initial Q waves than in those without (1044 [10%] vs 344 [7%],
      p<0.0001). These findings were similar in patients with a first acute myocardial
      infarction and when stratified by time to randomisation (0-2, >2-4, >4 h) and by
      acute myocardial infarction location (anterior or inferior). Both the presence of
      initial Q waves and time to randomisation were positive univariate predictors,
      but only the presence of initial Q waves independently predicted 30-day mortality
      on multivariate analysis (adjusted OR 1.44, 95% CI 1.25-1.65 with clinical
      indices, and 1.31, 1.12-1.54 with clinical plus ST indices included as
      predictors). INTERPRETATION: The presence of Q waves in the infarct leads at
      presentation of ST-elevation acute myocardial infarction independently predicts
      higher 30-day mortality in patients treated with fibrinolytic therapy. Therefore,
      a more aggressive approach to reperfusion might be warranted in these patients.

PMID- 16798390
TI  - Kuru in the 21st century--an acquired human prion disease with very long
      incubation periods.
AB  - BACKGROUND: Kuru provides the principal experience of epidemic human prion
      disease. Its incidence has steadily fallen after the abrupt cessation of its
      route of transmission (endocannibalism) in Papua New Guinea in the 1950s. The
      onset of variant Creutzfeldt-Jakob disease (vCJD), and the unknown prevalence of
      infection after the extensive dietary exposure to bovine spongiform
      encephalopathy (BSE) prions in the UK, has led to renewed interest in kuru. We
      investigated possible incubation periods, pathogenesis, and genetic
      susceptibility factors in kuru patients in Papua New Guinea. METHODS: We
      strengthened active kuru surveillance in 1996 with an expanded field team to
      investigate all suspected patients. Detailed histories of residence and exposure
      to mortuary feasts were obtained together with serial neurological examination,
      if possible. FINDINGS: We identified 11 patients with kuru from July, 1996, to
      June, 2004, all living in the South Fore. All patients were born before the
      cessation of cannibalism in the late 1950s. The minimum estimated incubation
      periods ranged from 34 to 41 years. However, likely incubation periods in men
      ranged from 39 to 56 years and could have been up to 7 years longer. PRNP
      analysis showed that most patients with kuru were heterozygous at polymorphic
      codon 129, a genotype associated with extended incubation periods and resistance
      to prion disease. INTERPRETATION: Incubation periods of infection with human
      prions can exceed 50 years. In human infection with BSE prions, species-barrier
      effects, which are characteristic of cross-species transmission, would be
      expected to further increase the mean and range of incubation periods, compared
      with recycling of prions within species. These data should inform attempts to
      model variant CJD epidemiology.

PMID- 16798391
TI  - Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate
      mefloquine in falciparum malaria: an open-label randomised comparison.
AB  - BACKGROUND: Artemisinin-based combinations are judged the best treatments for
      multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefloquine is
      widely recommended in southeast Asia, but its high cost and tolerability profile
      remain obstacles to widespread deployment. To assess whether dihydroartemisinin
      piperaquine is a suitable alternative to artesunate-mefloquine, we compared the
      safety, tolerability, efficacy, and effectiveness of the two regimens for the
      treatment of uncomplicated falciparum in western Myanmar (Burma). METHODS: We did
      an open randomised comparison of 3-day regimens of artesunate-mefloquine (12/25
      mg/kg) versus dihydroartemisinin-piperaquine (6.3/50 mg/kg) for the treatment of
      children aged 1 year or older and in adults with uncomplicated falciparum malaria
      in Rakhine State, western Myanmar. Within each group, patients were randomly
      assigned supervised or non-supervised treatment. The primary endpoint was the PCR
      confirmed parasitological failure rate by day 42. Failure rates at day 42 were
      estimated by Kaplan-Meier survival analysis. This study is registered as an
      International Standard Randomised Controlled Trial, number ISRCTN27914471.
      FINDINGS: Of 652 patients enrolled, 327 were assigned dihydroartemisinin
      piperaquine (156 supervised and 171 not supervised), and 325 artesunate
      mefloquine (162 and 163, respectively). 16 patients were lost to follow-up, and
      one patient died 22 days after receiving dihydroartemisinin-piperaquine.
      Recrudescent parasitaemias were confirmed in only two patients; the day 42
      failure rate was 0.6% (95% CI 0.2-2.5) for dihydroartemisinin-piperaquine and 0
      (0-1.2) for artesunate-mefloquine. Whole-blood piperaquine concentrations at day
      7 were similar for patients with observed and non-observed dihydroartemisinin
      piperaquine treatment. Gametocytaemia developed more frequently in patients who
      had received dihydroartemisinin-piperaquine than in those on artesunate
      mefloquine: day 7, 18 (10%) of 188 versus five (2%) of 218; relative risk 4.2
      (1.6-11.0) p=0.011. INTERPRETATION: Dihydroartemisinin-piperaquine is a highly
      efficacious and inexpensive treatment of multidrug-resistant falciparum malaria
      and is well tolerated by all age groups. The effectiveness of the unsupervised
      treatment, as in the usual context of use, equalled its supervised efficacy,
      indicating good adherence without supervision. Dihydroartemisinin-piperaquine is
      a good alternative to artesunate-mefloquine.

PMID- 16798392
TI  - Gastro-oesophageal reflux disease.
AB  - Gastro-oesophageal reflux disease refers to reflux of gastric contents into the
      oesophagus leading to oesophagitis, reflux symptoms sufficient to impair quality
      of life, or long-term complications. Transient relaxation of the lower
      oesophageal sphincter is believed to be the primary mechanism of the disease
      although the underlying cause remains uncertain. Obesity and smoking are weakly
      associated with the disease and genetic factors might be important. A negative
      association with Helicobacter pylori exists, but eradication of H pylori does not
      seem to cause reflux disease. Diagnosis is imprecise as there is no gold
      standard. Reflux symptoms are helpful in diagnosis but they lack sensitivity.
      Ambulatory oesophageal pH monitoring also seems to be insensitive despite high
      specificity. Empirical acid suppression with a proton-pump inhibitor (PPI) has
      reasonable sensitivity but poor specificity. Some evidence suggests that once
      patients develop the disease, severity is determined early and patients seem to
      continue with that phenotype long term. Unfortunately, most patients do not
      respond to life-style advice and require further therapy. H2 receptor antagonists
      and PPIs are better than placebo in oesophagitis, with a number needed to treat
      of five and two, respectively. In non-erosive reflux disease, acid suppression is
      better than placebo but the response rate is lower. Most patients need long-term
      treatment because the disease usually relapses. The role of endoscopic therapy is
      uncertain. Anti-reflux surgery is probably as effective as PPI therapy although
      there is a low operative mortality and morbidity.

PMID- 16798393
TI  - Climate change and human health: impacts, vulnerability, and mitigation.
AB  - It is now widely accepted that climate change is occurring as a result of the
      accumulation of greenhouse gases in the atmosphere arising from the combustion of
      fossil fuels. Climate change may affect health through a range of pathways--eg,
      as a result of increased frequency and intensity of heat waves, reduction in cold
      related deaths, increased floods and droughts, changes in the distribution of
      vector-borne diseases, and effects on the risk of disasters and malnutrition. The
      overall balance of effects on health is likely to be negative and populations in
      low-income countries are likely to be particularly vulnerable to the adverse
      effects. The experience of the 2003 heat wave in Europe shows that high-income
      countries might also be adversely affected. Adaptation to climate change requires
      public-health strategies and improved surveillance. Mitigation of climate change
      by reducing the use of fossil fuels and increasing the use of a number of
      renewable energy technologies should improve health in the near term by reducing
      exposure to air pollution.

PMID- 16798394
TI  - Reform of drug control policy for palliative care in Romania.
AB  - Unrelieved pain from cancer and HIV/AIDS is a substantial worldwide public-health
      problem. Inadequate pain relief is partly due to excessively strict national drug
      control policies that constrain medical use of essential medicines such as
      morphine. Romania's drug-control policies are more than 35 years old and impose
      an antiquated regulatory system that is based on inpatient post-surgical
      management of acute pain that restricts prescription authority and makes access
      to opioid treatment difficult for outpatients with severe chronic pain due to
      cancer or HIV/AIDS. A Ministry of Health palliative-care commission used WHO
      guidelines to assess and recommend changes to Romania's national drug control law
      and regulations. The Romanian parliament has adopted a new law that will simplify
      prescribing requirements and allow modern pain management. Achievement of
      adequate pain relief is a vital part of worldwide health and will be dependent on
      reform of antidrug regulations in many countries.

PMID- 16798395
TI  - Awareness of rheumatic heart disease.

PMID- 16798396
TI  - Audiovestibular dysfunction in alcohol dependence. Are we worried?
AB  - PURPOSE: To study the audiovestibular function in patients of long-term alcohol
      dependence and compare these changes with social users of alcohol and complete
      abstainers. MATERIAL AND METHODS: This was a prospective study of 20 randomly
      selected patients of long-term alcohol dependence fulfilling International
      Statistical Classification of Diseases, 10th Revision criteria of alcohol
      dependence. Audiovestibular function in this group was compared with social user
      of alcohol and complete abstainers. RESULTS: Statistically significant elevations
      of thresholds were found at higher frequencies (4000 and 8000 Hz ) in the alcohol
      dependent group (P < .001). Alcohol-dependent patients had elevated thresholds at
      4 and 8 kHz. Brainstem-evoked response audiometry showed prolongation of
      latencies of waves I, III, and V alone with interpeak latencies of I-III and III
      V. One third of alcohol-dependent patients had abnormal electronystagmographic
      (ENG) findings. Abnormal ENG findings were only seen in alcohol-dependent
      patients with vertigo. There was no significant correlation between duration of
      alcohol dependence and abnormal ENG. CONCLUSIONS: Elevated thresholds at higher
      frequencies can be the only abnormality in alcohol-dependent patients. Presence
      of vertigo in alcohol-dependent patient may be associated with abnormal ENG
      findings. There is no correlation of duration of dependence and ENG
      abnormalities.

PMID- 16798397
TI  - Recurrent aphthous stomatitis: investigation of possible etiologic factors.
AB  - OBJECTIVE: To investigate the association of serum vitamin B(12), folic acid,
      iron, calcium, magnesium, and phosphorus levels as well as family history and
      cigarette smoking with recurrent aphthous stomatitis (RAS). METHODS: Thirty-four
      patients with RAS and 32 control subjects were included in this controlled
      prospective screening study. Both groups received a questionnaire, and serum
      screening tests were performed. The collected data were analyzed using chi(2)
      test and binary logistic regression analysis. RESULTS: Family history was found
      to be the most significant predisposing factor for RAS among the investigated
      ones. Regarding the serum tests, only vitamin B(12) was found to have significant
      correlation with RAS. Patients with vitamin B(12) deficiency, positive family
      history, and nonsmoking status have been found to have the highest risk for
      having RAS. CONCLUSIONS: RAS is a multifactorial disease. Positive family
      history, vitamin B(12) deficiency, and nonsmoking status are among the important
      predisposing factors.

PMID- 16798398
TI  - Management of inverted papillomas of the nose and paranasal sinuses.
AB  - PURPOSE: Inverted papillomas (IPs), although histologically benign, are
      aggressive lesions that may recur after an excision. The objective of this study
      was to compare the surgical treatment options for IPs with an emphasis on the
      experience of our institution with midfacial degloving (MFD) and medial
      maxillectomy. MATERIALS AND METHODS: A retrospective review of the charts of
      patients with IP treated by MFD and medial maxillectomy was performed. An
      analysis of the recurrence rates of IPs in the literature for endoscopic surgery
      and lateral rhinotomy was also performed. RESULTS: Ninety-eight medial
      maxillectomy procedures via MFD were performed for IPs with a minimum of 2 years'
      follow-up (median = 5.1 years). Two patients were found to have recurrences
      (2.1%). The literature review revealed an average recurrence rate of 15.7% for
      lateral rhinotomy as compared with that of 19.6% for endoscopic surgery.
      CONCLUSION: Midfacial degloving balances acceptable cosmetic results with low
      recurrence rates. It allows for adequate exposure and resection without the scar
      of a lateral rhinotomy incision.

PMID- 16798399
TI  - Outcomes in children with perforated tympanic membranes after tympanostomy tube
      placement: results using a pilot treatment algorithm.
AB  - PURPOSE: The objective of this study was to examine the success of a pilot
      treatment algorithm for tympanic membrane perforations in children after
      tympanostomy tube placement. MATERIALS AND METHODS: A retrospective chart review
      of children with diagnosed tympanic membrane perforations after tympanostomy tube
      placement from 1998 to 2003 at a tertiary care children's hospital was performed.
      The patients had been treated according to an algorithm used by 2 pediatric
      otolaryngologists for management of tympanic membrane perforations: observation
      vs myringoplasty. Success rates were examined. RESULTS: Ninety-five children were
      identified, 27% of whom had nonhealing perforations after tube extrusion; 73% of
      the perforations were caused by a retained tube. The median duration of tube
      retention was 48 months, ranging from 13 to 120 months. After the treatment
      protocol, 76% of the patients underwent gelatin film or paper patch
      myringoplasty, 23% had adipose myringoplasty, and 1% were observed. Overall, 91%
      had healed perforations after the first intervention. Among those requiring a
      second intervention, the sizes of initial perforations were between 15% and 40%,
      with postrepair perforation sizes between 5% and 40%. In addition, 75% of those
      requiring a second intervention underwent tympanoplasty repair and 25% had fat
      patch myringoplasty. None required a third intervention. CONCLUSIONS: Our
      treatment algorithm for children with tympanic membrane perforations after
      tympanostomy tube placement appears to be successful and is an excellent model
      for other clinicians.

PMID- 16798400
TI  - Predicting deep neck space abscess using computed tomography.
AB  - PURPOSE: To investigate objective measures that could increase the positive
      predictive value of computed tomography (CT) in diagnosing deep neck space
      infections (DNSIs). METHODS: A retrospective analysis of patients surgically
      treated at a tertiary care hospital for DNSIs for more than 2 years were
      reviewed. Patients who had had CT with contrast scanning suggestive of deep neck
      space abscess within 24 hours before surgery were included. The average
      Hounsfield units for each abscess were calculated. Based on the intraoperative
      finding of pus, the patients were divided into groups. Student t tests compared
      the average Hounsfield units, white blood cell count, and maximum temperature
      between the groups. Outcomes were measured by comparing overall length of
      hospital stay, length of postoperative stay, and complications. RESULTS: Of the
      32 patients surgically drained, 24 (75%) had discreet collections of pus, whereas
      12 (25%) did not. Hounsfield unit measurement was not reliable in distinguishing
      abscess from phlegmon. None of the other clinical variables studied to
      distinguish abscess from phlegmon were statistically different either. A
      statistical difference between the 2 groups was not identified. CONCLUSION:
      Although CT with contrast plays an important role in the diagnosis and management
      of DNSIs, the decision for surgical drainage of an abscess should be made
      clinically. A negative exploration rate of nearly 25% despite careful selection
      criteria should be expected.

PMID- 16798401
TI  - Efficacy/safety of amoxicillin/clavulanate in adults with bacterial
      rhinosinusitis.
AB  - PURPOSE: Acute bacterial rhinosinusitis (ABRS) is a common and uncomfortable
      condition, frequently caused by Streptococcus pneumoniae or Haemophilus
      influenzae. Antibacterial resistance among these and other common respiratory
      pathogens is now widespread and of concern. Pharmacokinetically enhanced
      amoxicillin/clavulanate 2000/125 mg was developed to be effective against the
      common respiratory pathogens, including many resistant strains. MATERIALS AND
      METHODS: This open-label, noncomparative study assessed the bacteriologic and
      clinical efficacy of amoxicillin/clavulanate 2000/125 mg in adult patients with
      ABRS. Requirements for study entry included a clinical diagnosis of ABRS
      supported by radiologic findings. In addition, sinus puncture for bacteriologic
      assessment was required at study entry. RESULTS: Overall, bacteriologic success
      (eradication or clinical evidence of eradication) at the follow-up visit (days 17
      28) was achieved in 87.8% (722/822) of patients with 1 or more pathogen isolated
      at screening, in 93.2% (246/264) of patients with S pneumoniae, in 96.7% (29/30)
      of those with penicillin-resistant S pneumoniae (penicillin minimum inhibitory
      concentrations >or=2 microg/mL), and in 88.7% (110/124) of patients with beta
      lactamase-positive pathogens. Bacteriologic success was achieved against 6 of 7 S
      pneumoniae isolates with amoxicillin/clavulanic acid minimum inhibitory
      concentrations of 4/2 microg/mL or higher. CONCLUSIONS: Amoxicillin/clavulanate
      2000/125 mg was generally well tolerated. This new amoxicillin/clavulanate
      formulation provides a suitable option for empiric therapy for ABRS in adults.

PMID- 16798402
TI  - Successful cochlear implantation in a patient with superficial siderosis.
AB  - OBJECTIVE: To define the presentation and outcome of cochlear implantation in a
      patient with profound sensorineural hearing loss due to superficial siderosis.
      STUDY DESIGN: Retrospective case review. RESULTS: Postimplantation speech
      reception threshold was 34 dB, and hearing in noise testing sentences were 71%
      demonstrating a successful outcome. These results have been maintained for 5
      years after implantation. CONCLUSION: Cochlear implantation is a potentially
      successful rehabilitation option for certain patients with profound sensorineural
      hearing loss due to superficial siderosis.

PMID- 16798403
TI  - Solitary fibrous tumor of the retropharynx causing obstructive sleep apnea.
AB  - Solitary fibrous tumors (SFTs) are rare, usually benign, spindle cell neoplasms
      that most often originate near mesothelium-lined surfaces of the pleural or
      peritoneal cavity. SFTs reported in the head and neck occur most commonly in the
      oral cavity, sinonasal tract, and orbit. We report a case of SFT of the
      retropharynx causing severe obstructive sleep apnea. The diagnostic and
      management strategies of SFTs are discussed.

PMID- 16798404
TI  - Unilateral multifocal inverted papilloma of the maxillary and frontal sinus.

PMID- 16798405
TI  - Image-guided endoscopic endonasal resection of a recurrent craniopharyngioma.

PMID- 16798406
TI  - Use of the palatal flap for closure of an oronasal fistula.
AB  - Palatal obturators are frequently used in the initial treatment of postoperative
      palatal fistulae to address the associated problems experienced with speech and
      swallowing. Many reconstructive surgical techniques for palatal defects have been
      reported. Although palatal-based flaps are less frequently reported, they can
      offer a relatively simple reconstructive option with minimal morbidity in
      patients with acquired palatal defects. We present a case report of a patient
      requiring reconstruction of a midline oronasal fistula after resection of a
      palatal malignancy and review the literature concerning this technique.

PMID- 16798407
TI  - Lipoma of the cerebellopontine angle.
AB  - Lipomas of the cerebellopontine angle (CPA) are unusual tumors that typically
      present with hearing loss, tinnitus, dizziness, and occasionally facial
      neuropathies. We describe the case of a healthy 42-year-old woman who presented
      with left-sided hearing loss and facial synkinesis. T1-weighted magnetic
      resonance imaging revealed an enhancing lesion of the left CPA with no signal on
      fat suppression sequences. Despite conservative therapy, the patient developed
      progressive hemifacial spasm, and a suboccipital craniotomy approach was used to
      debulk the tumor, which encased cranial nerves V, VII, VIII, IX, X, and XI.
      Surgical histopathology demonstrated mature adipocytes, consistent with lipoma.
      Two years after surgery, the patient remains free of facial nerve symptoms.
      Cerebellopontine angle lipomas are rare lesions of the skull base and are
      reliably diagnosed with T1-weighted and fat suppression magnetic resonance
      sequences, which we recommend in the routine radiologic workup of CPA tumors.
      Accurate preoperative diagnosis is crucial because most CPA lipomas should be
      managed conservatively. Partial surgical resection is indicated only to alleviate
      intractable cranial neuropathies or relieve brainstem compression.

PMID- 16798408
TI  - Inflammatory pseudotumor of the nasal cavity.
AB  - Inflammatory pseudotumor is usually found in the orbits and lungs, but rarely in
      the sinonasal area. We present a 59-year-old woman with a right nasal mass. This
      lesion caused nasal bleeding and blockage. Image study showed that the solid mass
      eroded the bony structure and pushed the nasal septum toward the left side. Wide
      excision was done via lateral rhinotomy. Although its clinical picture mimicked a
      malignant tumor, histological examination showed an inflammatory process composed
      of a mixture of lymphoplasmacytic infiltrate, histiocytic cells, and spindled
      fibroblastic/myofibroblastic cells. Both culture and pathology identified no
      microorganism. No evidence of recurrence was found after follow-up for more than
      2.5 years. The clinical behavior of inflammatory pseudotumor was confusing and
      tended to be mistaken as malignancy. Its diagnosis and management could be a
      great challenge for clinicians.

PMID- 16798409
TI  - Asymptomatic retropharyngeal abscess related to cervical Pott's disease.
AB  - Pott's disease is an uncommon manifestation of tuberculosis, which usually
      involves thoracic or lumbar vertebrae. The body of the vertebrae is most severely
      affected and a compression fracture is an almost inevitable consequence of the
      disease. A paravertabral abscess generally accompanies vertebral involvement.
      Tenderness over the involved vertebrae, weakness of the related muscles, and
      paraesthesia are the usual symptoms. In this article, we report a case of
      cervical Pott's disease presenting mainly with neurologic symptoms such as
      weakness, pain, numbness of both arms and hands, and an asymptomatic
      retropharyngeal abscess.

PMID- 16798410
TI  - Brown tumors of the jaws associated with primary or secondary
      hyperparathyroidism. A clinical study and review of the literature.
AB  - PURPOSE: The aim of this article is to present the development of brown tumors in
      the jaws as a definite feature of hyperparathyroidism (HPT), whether primary or
      secondary. PATIENTS AND METHODS: The study included 2 cases of primary HPT and 3
      cases of secondary HPT associated with brown tumors in the jaws. The patients
      presented in our clinic at the "G. Papanikolaou" Hospital in Thessaloniki for
      treatment of their disease. The patients were 4 women and 1 man, and patient's
      ages ranged from 21 to 76 years. Four cases of the brown tumors involved the
      mandible, and 1 case involved the maxilla and the maxillary sinus. The surgical
      excision of bone lesions and treatment of primary or secondary HPT were performed
      on the patients in our study. RESULTS: Patient 1 (primary HPT, caused by an
      adenoma of the right parathyroid glands) was treated with surgical removal of the
      maxillary lesion and excision of the adenoma. Three years later, the patient is
      free of the disease, with no recurrence of the brown tumor. Patient 2 (primary
      HPT, caused by an adenoma of the right parathyroid glands) was treated with
      excision of the adenoma. One year later, a second bone lesion developed in the
      mandible, and 3(1/2) of the fourth parathyroid (right) glands was removed. The
      patient is being observed. The other 3 patients with brown tumors associated with
      secondary HPT were treated with excision of the bone lesions; HPT was treated
      with hemodialysis (2 patients) and renal transplantation (1 patient). For the
      patients treated with hemodialysis, the disease is under control and there is no
      recurrence of the brown tumors. The patient who underwent transplantation is free
      of the disease 7 years later. CONCLUSIONS: Primary or secondary HPT may be
      recognized by the presence of an osteolytic lesion with giant cells, a condition
      referred as "brown tumor." The most useful therapy for patients with brown tumors
      is surgical excision of bone lesions and therapy (surgical or medical) for
      primary or secondary HPT.

PMID- 16798411
TI  - Endoscopic treatment of ethmoidal hemangioendothelioma: case report and review of
      the literature.
AB  - Hemangioendothelioma (HE) is a rare vascular tumor of endothelial cell origin
      that usually involves long bone or soft tissue. However, there are cases of head
      and neck involvement. In the literature, only 19 cases of nasal involvement are
      described. We report a case of an 18-month-old child who had HE of the ethmoid
      sinus. Endoscopic resection of the tumor was performed. The patient is well
      without any recurrence after 4 years of follow-up. Because of its rarity, the
      literature on HE in the nasal cavity and paranasal sinus is reviewed and its
      management is discussed.

PMID- 16798412
TI  - Diagnosis and management of aggressive, acquired cholesteatoma with skull base
      and calvarial involvement: a report of 3 cases.
AB  - A prospective case review of 3 patients treated at a tertiary referral center
      from 1997 to 2002 are presented. Three men, age 30 to 68 (mean, 45) years, were
      treated for acquired cholesteatoma with skull base invasion. Two patients had no
      prior otological surgery, and 1 was detected after 4 prior mastoid procedures.
      One presented with progressive unilateral facial palsy, 1 with otorrhea, and 1
      with temporal mass above a modified radical mastoidectomy cavity. All 3 patients
      were treated with single-staged canal wall-down mastoidectomy. Patients were
      followed up with otoscopy and neuroimaging from 40 to 61 months. Two patients had
      no recurrence of cholesteatoma, and 1 had squamous debris in the mastoid cavity
      removed in the outpatient clinic. One had complete ipsilateral facial nerve
      paralysis preoperatively and recovered to House-Brackmann grade III within 1 year
      of surgery. Patient 1 had labyrinthine involvement before surgery and had
      ipsilateral anacusis after resection and repair. No other complications occurred.
      Initial presentation, workup, surgical challenges, disease follow-up, facial
      nerve function, hearing results, and complications are reported.

PMID- 16798413
TI  - Pharyngeal diverticulum as a sequela of anterior cervical fusion.
AB  - A rarely diagnosed etiology of dysphagia is a pharyngeal diverticula occurring
      after anterior cervical fusion. Here we review 2 cases where patients developed
      pharyngeal diverticula following anterior cervical fusion. The first patient was
      a 28-year-old female who presented with regurgitation following C5 through C6
      cervical fusion. She was diagnosed with a pharyngeal diverticulum and underwent
      open repair, but began to experience symptoms again a few months later. A barium
      swallow showed a recurrent pharyngeal diverticulum. Endoscopic repair was
      attempted; however, because of the thick scar band between the diverticulum and
      the esophagus, the operation had to be converted to an open repair with
      cricopharyngeal myotomy. The second case involved a 63-year-old male who
      presented with dysphagia and regurgitation 6 months after anterior cervical
      fusion. Esophagram demonstrated a small diverticulum at the right lateral border
      of the upper esophagus. Open repair of the diverticulum with cricopharyngeal
      myotomy was successfully performed. Pharyngeal diverticula after anterior cevical
      fusion have only been reported in 2 prior cases in the literature. Here we
      describe 2 additional cases at our institution, both requiring open repair.
      Radiographic studies demonstrate the diverticulum at the site of scarring from
      the cervical fusion. Because of the thick scar band and the atypical location of
      these diverticula, endoscopic repair with stapping (as done for Zenker's
      diverticula) may not be feasible. These cases highlight the importance of
      considering a diverticulum in the differential of posoperative patients
      presenting to the otolaryngologists with complaints of dysphagia following
      cevical spine surgery.

PMID- 16798415
TI  - Defining biochemical failure following radiotherapy with or without hormonal
      therapy in men with clinically localized prostate cancer: recommendations of the
      RTOG-ASTRO Phoenix Consensus Conference.
AB  - In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO)
      sponsored a Consensus Conference to establish a definition of biochemical failure
      after external beam radiotherapy (EBRT). The ASTRO definition defined prostate
      specific antigen (PSA) failure as occurring after three consecutive PSA rises
      after a nadir with the date of failure as the point halfway between the nadir
      date and the first rise or any rise great enough to provoke initiation of
      therapy. This definition was not linked to clinical progression or survival; it
      performed poorly in patients undergoing hormonal therapy (HT), and backdating
      biased the Kaplan-Meier estimates of event-free survival. A second Consensus
      Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in
      Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel
      recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the
      standard definition for biochemical failure after EBRT with or without HT; (2)
      the date of failure be determined "at call" (not backdated). They recommended
      that investigators be allowed to use the ASTRO Consensus Definition after EBRT
      alone (no hormonal therapy) with strict adherence to guidelines as to "adequate
      follow-up." To avoid the artifacts resulting from short follow-up, the reported
      date of control should be listed as 2 years short of the median follow-up. For
      example, if the median follow-up is 5 years, control rates at 3 years should be
      cited. Retaining a strict version of the ASTRO definition would allow comparisons
      with a large existing body of literature.

PMID- 16798416
TI  - TGFbeta1 polymorphisms and late clinical radiosensitivity in patients treated for
      gynecologic tumors.
AB  - PURPOSE: To investigate the association between six transforming growth factor
      beta1 gene (TGFbeta1) polymorphisms (-1.552delAGG, -800G>A, -509C>T, Leu10Pro,
      Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after
      gynecologic radiotherapy (RT). METHODS AND MATERIALS: Seventy-eight women with
      cervical or endometrial cancer and 140 control individuals were included in the
      study. According to the Common Terminology Criteria for Adverse Events version
      3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of
      whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP), single base extension and genotyping
      assays were performed to examine the polymorphic sites in TGFbeta1. RESULTS:
      Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with
      the risk of developing late severe RT reactions. Triple (variant) homozygous
      patients had a 3.6 times increased risk to develop severe RT reactions (p=0.26).
      Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were
      associated with clinical radiosensitivity. There was perfect linkage
      disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and
      tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype
      analysis revealed two major haplotypes but could not distinguish radiosensitive
      from nonradiosensitive patients. CONCLUSIONS: The present study shows that
      homozygous variant TGFbeta1 -1.552delAGG, -509TT, and 10Pro genotypes may be
      associated with severe clinical radiosensitivity after gynecologic RT.

PMID- 16798417
TI  - Reporting and analyzing statistical uncertainties in Monte Carlo-based treatment
      planning.
AB  - PURPOSE: To investigate methods of reporting and analyzing statistical
      uncertainties in doses to targets and normal tissues in Monte Carlo (MC)-based
      treatment planning. METHODS AND MATERIALS: Methods for quantifying statistical
      uncertainties in dose, such as uncertainty specification to specific dose points,
      or to volume-based regions, were analyzed in MC-based treatment planning for 5
      lung cancer patients. The effect of statistical uncertainties on target and
      normal tissue dose indices was evaluated. The concept of uncertainty volume
      histograms for targets and organs at risk was examined, along with its utility,
      in conjunction with dose volume histograms, in assessing the acceptability of the
      statistical precision in dose distributions. The uncertainty evaluation tools
      were extended to four-dimensional planning for application on multiple instances
      of the patient geometry. All calculations were performed using the Dose Planning
      Method MC code. RESULTS: For targets, generalized equivalent uniform doses and
      mean target doses converged at 150 million simulated histories, corresponding to
      relative uncertainties of less than 2% in the mean target doses. For the normal
      lung tissue (a volume-effect organ), mean lung dose and normal tissue
      complication probability converged at 150 million histories despite the large
      range in the relative organ uncertainty volume histograms. For "serial" normal
      tissues such as the spinal cord, large fluctuations exist in point dose relative
      uncertainties. CONCLUSIONS: The tools presented here provide useful means for
      evaluating statistical precision in MC-based dose distributions. Tradeoffs
      between uncertainties in doses to targets, volume-effect organs, and "serial"
      normal tissues must be considered carefully in determining acceptable levels of
      statistical precision in MC-computed dose distributions.

PMID- 16798418
TI  - Impact of geometrical uncertainties on 3D CRT and IMRT dose distributions for
      lung cancer treatment.
AB  - PURPOSE: To quantify the effect of set-up errors and respiratory motion on dose
      distributions for non-small cell lung cancer (NSCLC) treatment. METHODS AND
      MATERIALS: Irradiations of 5 NSCLC patients were planned with 3 techniques, two
      (conformal radiation therapy (CRT) and intensity modulated radiation therapy
      (IMRT1)) with a homogeneous dose in the planning target volume (PTV) and a third
      (IMRT2) with dose heterogeneity. Set-up errors were simulated for gross target
      volume (GTV) and organs at risk (OARs). For the GTV, the respiration was also
      simulated with a periodical motion around a varying average. Two configurations
      were studied for the breathing motion, to describe the situations of free
      breathing (FB) and respiration-correlated (RC) CT scans, each with 2 amplitudes
      (5 and 10 mm), thus resulting in 4 scenarios (FB_5, FB_10, RC_5 and RC_10). Five
      thousand treatment courses were simulated, producing probability distributions
      for the dosimetric parameters. RESULTS: For CRT and IMRT1, RC_5, RC_10 and FB_5
      were associated with a small degradation of the GTV coverage. IMRT2 with FB_10
      showed the largest deterioration of the GTV dosimetric indices, reaching 7% for
      Dmin at the 95% probability level. Removing the systematic error due to the
      periodic breathing motion was advantageous for a 10 mm respiration amplitude. The
      estimated probability of radiation pneumonitis and acute complication for the
      esophagus showed limited sensitivity to geometrical uncertainties. Dmax in the
      spinal cord and the parameters predicting the risk of late esophageal toxicity
      were associated to a probability up to 50% of violating the dose tolerances.
      CONCLUSIONS: Simulating the effect of geometrical uncertainties on the individual
      patient plan should become part of the standard pre-treatment verification
      procedure.

PMID- 16798419
TI  - The importance of radiotherapy in AT/RT patients less than 3 years of age: in
      regards to Chen et al. (Int J Radiat Oncol Biol Phys 2006;64:1038-1043).

PMID- 16798421
TI  - Integral radiation dose to normal structures with conformal external beam
      radiation: in regards to Aoyama et al. (Int J Radiat Oncol Biol Phys 2006;64:962
      967).

PMID- 16798423
TI  - Target contouring protocol for 3D conformal radiotherapy in lung cancer.

PMID- 16798426
TI  - Surgical anatomy of the nail apparatus.
AB  - Nail surgery is an integral part of dermatologic surgery. An in-depth knowledge
      of the anatomy, biology, physiology, and gross pathology of the entire nail unit
      is essential. In particular, knowledge of nail histopathology is necessary to
      perform diagnostic nail biopsies and other nail procedures correctly.

PMID- 16798427
TI  - Common nail tumors.
AB  - Nail abnormalities are varied and numerous. They include warts, keratoacanthomas,
      onychomatricomas, fibrokeratomas, osteochondromas, tumors (ie, glomus, giant
      cell, Koenen's, and others), and Bowen's disease. Although the gravity of these
      conditions may vary, prompt diagnosis and treatment is of the utmost importance.
      This article discusses the most common defects associated with the nail unit and
      its surrounding tissue, as well as the differential diagnosis and treatment of
      these conditions.

PMID- 16798428
TI  - Basic nail surgery.
AB  - Patients often fear nail surgery because of the pain associated with anesthesia
      and post-operative care. Potential dystrophic sequelae are of concern to the
      practitioner. A thorough knowledge of the techniques of anesthesia, nail anatomy,
      and surgical procedures is a prerequisite for successful nail surgery with almost
      no pain and minimal scarring. It also is mandatory to involve a
      dermatopathologist who is familiar with the histologic idiosyncrasies of the nail
      unit.

PMID- 16798429
TI  - Ultrasound imaging of nails.
AB  - The nail apparatus contains tissues of various echogenicities and is thus well
      suited for ultrasound examination. Furthermore, ultrasonography is widely
      available and non-invasive and may therefore be used for longitudinal studies of
      tissues and diseases. Characteristic ultrasound pictures can be seen in
      psoriasis, cysts, vascular abnormalities,and other nail diseases. Ultrasound
      examination can visualize and quantify morphologic and functional aspects of nail
      biology.

PMID- 16798430
TI  - Pigmented nail disorders.
AB  - Nail pigmentation is defined by the presence of melanin in the nail plate. It
      most frequently has the appearance of a longitudinal pigmented band, called
      longitudinal mel-anonychia (LM). LM is an important aspect of ungual pathology
      because it can be the first sign of nail apparatus melanoma. The aim of this
      article is to help distinguish those types of melanonychia that are worrisome and
      should lead to biopsy from those that are reasonably reassuring and need only be
      followed clinically. Histology, differential diagnosis, and biopsy techniques
      also are considered.

PMID- 16798431
TI  - The nail in systemic diseases.
AB  - Although abnormalities of the nails have been reported in different systemic
      disorders,most of these abnormalities are nonspecific. This article reports and
      discusses only those nail signs that provide the clinician with clues for the
      diagnosis of systemic disorders.

PMID- 16798432
TI  - Common nail disorders.
AB  - Common skin diseases often present with nail changes. This article reviews the
      nail manifestations of psoriasis, lichen planus, alopecia areata, and twenty-nail
      dystrophy. There is considerable overlap in the nail findings in these cutaneous
      conditions, but nail changes distinct to each do exist.

PMID- 16798433
TI  - Childhood nail diseases.
AB  - The diagnosis of pediatric nail populations is complicated because a large
      proportion of pediatric nail presentations involve parents bringing in their
      children with questions regarding nail appearance rather than the plain
      presentation of a disease or functional problem. Parents are concerned whether
      the nails are normal, if they are uncomfortable for the baby or child, if the
      nails will affect walking or other future function, or if the changes are of
      wider significance and suggest more sinister medical problems than are yet
      apparent. To address these concerns, the clinician needs a good grasp of what is
      normal.

PMID- 16798434
TI  - Diagnosing onychomycosis.
AB  - Onychomycosis is the most prevalent nail disease, representing nearly half of all
      clinically diagnosed onychopathies. Given the pervasive nature of the disease and
      that successful treatment depends on the proper identification of the causative
      organism,accurate and reliable methods of diagnosis are necessary. This article
      discusses the efficacy of the various methods used for the diagnosis of
      onychomycosis.

PMID- 16798435
TI  - Spotlight on nail histomycology.
AB  - The misdiagnosis of onychomycosis delays the proper treatment of the nail
      condition. Nail histomycology refers to the microscopic examination of histologic
      sections prepared from nail clippings for the purpose of detecting the presence
      of fungi. This laboratory method is the most sensitive procedure for the
      diagnosis of onychomycosis. It allows for the visualization of the precise
      location of the invasive fungus inside the nail apparatus. The method also
      distinguishes various shapes of the fungal cells, in particular filamentous
      fungi, yeasts, conidia, and sporodochia. The correct diagnosis provided by
      histomycology combined with culture not only allows for more efficient
      expenditure of funds and services but also is important for the timely
      alleviation of the disorder.

PMID- 16798436
TI  - Therapies for onychomycosis: a review.
AB  - Onychomycosis, a chronic fungal infection of the nail, can be treated using
      various modalities. Surgical, chemical, topical, and oral methods are reviewed in
      this article, with an emphasis on the three systemic treatments approved by the
      US Food and Drug Administration: terbinafine, itraconazole, and griseofulvin.

PMID- 16798437
TI  - Onychomycosis therapies: strategies to improve efficacy.
AB  - The combination of relatively high treatment failure rates and infection relapse
      rates warrants consideration of ways in which antifungal therapy can be delivered
      so that efficacy rates can be improved. These involve the combination of
      available therapies and/or a modification of treatment regimens.

PMID- 16798438
TI  - Drug-induced nail diseases.
AB  - Although many nail disorders have been associated with drug intake, most reports
      are anecdotal. Most nail changes caused by drugs are the outcome of acute
      toxicity to the nail epithelia; nail symptoms depend on which nail structure is
      damaged. The most com-mon symptoms include Beau's lines/onychomadesis,
      melanonychia, onycholysis, and periungual pyogenic granulomas. Drug-induced nail
      abnormalities are usually transitory and disappear with drug withdrawal, but
      sometimes persist over time. This article reviews drugs that have been
      consistently associated with nail abnormalities.

PMID- 16798439
TI  - Nail cosmetics.
AB  - Nail cosmetics are used worldwide by millions of women who desire attractive,
      adorned nails. Smooth, shiny fingernails and toenails are highly desirable and an
      entire industry is devoted to achieving that end for the consumer. The grooming
      and decoration of nails is a well-ingrained cultural ritual in many countries of
      the world. In the United States alone, US dollars 6.4 billion was spent on nail
      salon services in the year 2004.

PMID- 16798440
TI  - Municipal solid waste management as a luxury item.

PMID- 16798441
TI  - Post cesarean delivery pain management: multimodal approach.

PMID- 16798442
TI  - Incisional and epidural analgesia after caesarean delivery: a prospective,
      placebo-controlled, randomised clinical study.
AB  - BACKGROUND: This study evaluated efficacy, safety and patient satisfaction with
      incisional analgesia with a subfascial catheter compared to epidural analgesia
      for pain relief following caesarean section. METHODS: Forty patients were
      randomised after elective caesarean section to receive either intermittent 10-mL
      boluses of 0.125% levobupivacaine into the epidural space and physiologic saline
      into the surgical wound or intermittent 10-mL boluses of 0.25% levobupivacaine
      into the wound and epidural saline with a repeated 10-dose regimen. Analgesic
      efficacy was evaluated by numerical pain scores (0-10, 0=no pain, 10=worst pain)
      and based on the consumption of supplemental opioid. Side effects, patient
      satisfaction and plasma concentrations of levobupivacaine were recorded. RESULTS:
      In the epidural group average pain scores were lower (1.8 vs. 3, P=0.006) and the
      consumption of local anaesthetic (29 mL vs. 38 mL, P=0.01) was smaller during the
      first four postoperative hours, after which both groups had pain scores of 3 or
      less at rest. All parturients were able to walk after the 24-h study period. The
      total consumption of rescue opioid oxycodone (32 vs. 37 mg, P=0.6) during the
      whole 72-h study period was low in both study groups. Side effects were mild and
      rare. Satisfaction scores were equally high in the two groups. Peak plasma
      concentrations of levobupivacaine were below the toxic range. CONCLUSION:
      Incisional local analgesia via a subfascial catheter provided satisfactory pain
      relief with patient satisfaction comparable to that seen with epidural analgesia.
      This technique may be a good alternative to the more invasive epidural technique
      following caesarean section as a component of multimodal pain management.

PMID- 16798443
TI  - An analysis of the need for anesthetic interventions with differing
      concentrations of labor epidural bupivacaine: an observational study.
AB  - BACKGROUND: Labor epidural analgesia techniques using lower concentrations of
      bupivacaine are designed to maintain pain control with fewer side effects such as
      hypotension and motor block. However, the increase in sensation may allow
      breakthrough pain resulting in the need for additional interventions. We examined
      the number of interventions, both for analgesia and for treatment of side
      effects, required when using three concentrations of bupivacaine. METHODS:
      Retrospective observational investigation examining 4493 women who received
      epidural analgesia during two periods. In the first period, higher concentrations
      of bupivacaine were used (0.125% and 0.0625%, both with fentanyl 2 microg/mL). In
      the second period, a very low concentration was used (0.04% plus fentanyl 1.7
      microg/mL and epinephrine 1.7 microg/mL). Outcomes were compared using univariate
      tests, and multivariate Poisson regression was used to identify independent
      factors influencing interventions. RESULTS: The frequencies of interventions were
      similar for women receiving bupivacaine concentrations of 0.04% (1.4+/-2.0) and
      0.125% (1.5+/-2.0), while women receiving the 0.0625% solution required more
      interventions (1.8+/-2.3; P<0.001). Women who received 0.04% or 0.0625%
      bupivacaine required more treatment of breakthrough pain (P<0.002), while those
      receiving 0.125% bupivacaine required more treatment for hypotension and motor
      block (P<0.05). Multivariate Poisson regression showed that duration of
      treatment, maternal age and body mass index were independent factors for the
      number of interventions. CONCLUSIONS: Neither the total interventions nor
      intervention rate per hour varied significantly with the concentrations of
      bupivacaine used in this study. Lower concentrations produced fewer side effects
      including hypotension, while the higher concentration resulted in less
      breakthrough pain.

PMID- 16798444
TI  - A randomised double-blinded controlled trial of the effect of diluent volume on
      the efficacy of a single dose of epidural ropivacaine for labour analgesia.
AB  - BACKGROUND: Few studies have systematically investigated the effect of diluent
      volume on the efficacy of epidural local anaesthetics for labour analgesia and no
      data are available for ropivacaine. Our aim was to compare epidural ropivacaine
      given in three different volumes for labour analgesia. METHODS: In a double
      blinded study, we randomly assigned 60 labouring parturients with cervical
      dilatation <5 cm to receive epidural ropivacaine 30 mg diluted to 5 mL (group 5,
      n=20), 10 mL (group 10, n=20) or 20 mL (group 20, n=20) for analgesia. We
      measured visual analogue scale pain scores at the peak of contraction for 30 min
      plus onset and duration of analgesia. RESULTS: Pain scores at 30 min were similar
      among group 5 (median 22 [interquartile range 0-44] mm), group 10 (9 [0-21] mm)
      and group 20 (37 [0-51] mm), P=0.35. The number of patients who achieved a
      decrease in pain score to < or =30% of baseline was similar among group 5 (12/20
      (60%)), group 10 (17/20 (85%)) and group 20 (11/19 (58%)), P=0.13. Onset and
      duration of analgesia, the incidence of motor block and patient satisfaction were
      similar among groups. CONCLUSIONS: Under the conditions of this study, within the
      range of 5-20 mL, the volume and concentration were not significant factors
      influencing the efficacy of a single 30-mg bolus of epidural ropivacaine given
      for labour analgesia. This suggests that the most important factor influencing
      analgesic efficacy was drug mass.

PMID- 16798445
TI  - Patient-controlled epidural analgesia: the role of epidural fentanyl in
      peripartum urinary retention.
AB  - BACKGROUND: Urinary bladder function is impaired during labor and delivery,
      predisposing to urinary retention. The effect of low-dose epidural opioid on
      bladder function remains unclear. We tested the hypothesis that adding low-dose
      fentanyl to epidural ropivacaine for patient-controlled labor analgesia does not
      promote urinary retention. METHODS: Laboring women who requested patient
      controlled epidural analgesia were randomly assigned in a double blind study to
      0.2% ropivacaine (R-group, n=100) or 0.2% ropivacaine with fentanyl 2 microg/mL
      (RF-group, n=98). Urinary bladder distension was assessed clinically every hour.
      The post-void residual urine volume was measured by ultrasonography. Urine volume
      exceeding 100 mL was drained by catheterization. Bladder volume of > or =300 mL,
      as determined by catheterization was considered as evidence of urinary retention.
      RESULTS: Thirty percent of the patients in each group developed urinary retention
      during labor. There was no statistically significant difference between the
      groups. There was an excellent correlation between bladder volume as estimated by
      ultrasonography and that by catheterization: catheterization volume=0.93 x
      ultrasound volume + 25; r(2)=0.83. The bias (mean error) was -1+/-99 mL and the
      precision (average absolute error) between the ultrasound estimate and actual
      bladder volume determined by catheterization was 58+/-79 mL. CONCLUSION: Addition
      of fentanyl to patient-controlled epidural analgesia did not increase the risk of
      urinary retention. Ultrasound measurements were effective and reliable in
      assessing urinary bladder volumes during labor.

PMID- 16798446
TI  - Adnexal mass surgery and anesthesia during pregnancy: a 10-year retrospective
      review.
AB  - BACKGROUND: Many studies have addressed the specific perinatal risks of surgery
      and anesthesia during pregnancy, but there is still much undetermined. The
      objective of this retrospective review was to compare the adverse pregnancy
      outcome in patients undergoing laparoscopy and laparotomy with inhalational or
      regional anesthesia for adnexal mass in pregnancy. METHOD: From the records, the
      case notes of patients who had had surgery for adnexal mass during pregnancy over
      10 years in the Cheil General Hospital and Women's Health Center were reviewed.
      The type of surgery and anesthesia and the outcome were recorded. RESULTS: Of the
      235 patients, general anesthesia was employed for laparotomy in 137 and for
      laparoscopic surgery in 27. Regional anesthesia for laparotomy was administered
      on 71 occasions. The incidence of preterm labor in the group given regional
      anesthesia (29.6%) was significantly higher than the groups given general
      anesthesia (5.8% in the laparotomy group, 0% in the laparoscopy group). The
      incidences of preterm labor and premature delivery in all surgical patients
      (preterm labor 12.3%, premature delivery 7.7%) were higher than among the non
      surgical pregnant population over the same period (3.2%, 4.8%). CONCLUSION:
      Patients undergoing laparotomy with regional anesthesia for adnexal mass in
      pregnancy may have higher risk of preterm labor than those given general
      inhalational anesthesia for laparotomy or laparoscopy. Therefore, if regional
      anesthesia is used for this type of surgery, then precautions should be taken to
      reduce the risk of preterm labor.

PMID- 16798447
TI  - A survey of labor patient-controlled epidural anesthesia practice in California
      hospitals.
AB  - BACKGROUND: Patient-controlled epidural analgesia (PCEA) offers many advantages
      over continuous epidural infusions for labor analgesia including fewer physician
      interventions, improved analgesia and satisfaction, and reduced local anesthetic
      doses. However, anesthesiologists have been slow to adopt this technique, first
      described in 1988. No previous studies have evaluated specific labor patient
      controlled epidural analgesia practices in the United States. The aim of this
      study was to determine labor epidural and patient-controlled epidural analgesia
      practices among California hospitals. METHODS: Following institutional review
      board exemption approval, an online survey was created using
      freeonlinesurveys.com. An anonymous survey was sent via e-mail to 230 California
      Society of Anesthesiologists' members chosen at random to represent their
      hospitals' labor analgesia practices. RESULTS: We received 133 replies from the
      230 survey requests sent, a 58% response rate. The median labor epidural rate
      among the hospitals involved was 65% (range 0-95%). Overall, only 25% of
      California hospitals use patient-controlled epidural analgesia for analgesia in
      labor, with greater use among hospitals with dedicated obstetric anesthesia
      coverage and larger numbers of deliveries. Reasons given for not using patient
      controlled epidural analgesia include cost, clinician preference, safety concerns
      and the inconvenience of change. CONCLUSIONS: Despite the potential advantages of
      patient-controlled epidural analgesia over continuous epidural infusions for
      labor analgesia, patient-controlled epidural analgesia has not been widely
      adopted in California hospitals. Education regarding this technique is needed to
      encourage its increased use.

PMID- 16798448
TI  - Reports on Confidential Enquiries into Maternal Deaths: management strategies
      based on trends in maternal cardiac deaths over 30 years.
AB  - In the latest Report of the Confidential Enquiries into Maternal and Child Health
      (CEMACH; formerly Confidential Enquiries into Maternal Deaths (CEMD)), cardiac
      disease was the second commonest cause of maternal mortality. Currently there is
      much emphasis on appropriate referral and multidisciplinary planning for women
      with known cardiac disease. However, examining all maternal cardiac deaths in the
      CEMACH/CEMD reports over the last 30 years, to see whether the condition was
      known before pregnancy or developed during pregnancy, suggests that while
      reported maternal mortality due to cardiac disease overall has approximately
      doubled, the number due to known disease has changed little. Thus significant and
      increasing numbers of deaths occur in women without known disease, either in
      those with risk factors or in those who develop conditions in the absence of risk
      factors. Therefore, while there is a continuing need to counsel, refer and
      appropriately manage women with known pre-existing cardiac disease, attention
      must also be paid to screening women before pregnancy for evidence of cardiac
      disease or risk factors, and also to cardiac disease that develops de novo during
      pregnancy, since early screening and referral strategies alone will not prevent
      units from encountering such cases. All units therefore require processes for
      monitoring and managing women for the development of cardiac disease throughout
      their pregnancies.

PMID- 16798449
TI  - Traditional rapid sequence induction is an outmoded technique for caesarean
      section and should be modified. Proposed.

PMID- 16798450
TI  - Traditional rapid sequence induction is an outmoded technique for Caesarean
      section and should be modified. Opposed.

PMID- 16798451
TI  - Foot drop after spinal anesthesia in a patient with a low-lying cord.
AB  - Damage to the spinal cord/conus medullaris due to incorrect identification of the
      lumbar space is a known complication of lumbar puncture. However, damage to a low
      lying cord using an appropriate interspace is extremely rare. We describe a 26
      year-old woman who underwent emergency caesarean section under spinal anesthesia.
      She developed right foot drop immediately after surgery, which gradually
      recovered over the next 10 months. Magnetic resonance imaging revealed a low
      lying cord with a fatty filum terminale and intramedullary T2 hyperintensity,
      suggestive of needle damage.

PMID- 16798452
TI  - Pneumocephalus with headache complicating labour epidural analgesia: should we
      still be using air?
AB  - Pneumocephalus is a rare complication of epidural block which typically occurs
      when the loss of resistance to air technique is used to identify the epidural
      space. We present a case of pneumocephalus with headache in a parturient
      following apparently uncomplicated labour epidural analgesia.

PMID- 16798453
TI  - Undiagnosed phaeochromocytoma mimicking severe preeclampsia in a pregnant woman
      at term.
AB  - We report an unusual case of phaeochromocytoma in pregnancy. The patient
      presented with severe hypertension, visual disturbances, proteinuria, glycosuria
      and pulmonary oedema at 38 weeks' gestation. The initial diagnosis was severe
      preeclampsia, but rapid deterioration of the fetus necessitated an emergency
      caesarean section under general anaesthesia, following which the maternal
      condition deteriorated rapidly. Differential diagnoses included pulmonary
      embolus, cardiomyopathy, amniotic fluid embolus and ischaemic/embolic
      cerebrovascular accident. Despite aggressive maximal treatment, mother and baby
      died 36 h later. Post mortem examination of the mother revealed a 5.5-cm tumour
      of the right adrenal gland confirmed histologically as a phaeochromocytoma. We
      examine the diagnostic dilemmas of this case and consider the treatment and
      management options when faced with a critically ill mother and the need to
      deliver her fetus by emergency caesarean section. We also question the clinical
      priorities during management of a sudden deterioration in both maternal and fetal
      health.

PMID- 16798454
TI  - Anesthetic management for emergency cesarean section in a patient with severe
      valvular disease and preeclampsia.
AB  - Wider selection of young patients for prosthetic valve replacement for valvular
      heart disease has resulted in an increase in number of women with heart disease
      reaching childbearing age. Such patients presenting in labor for emergency
      cesarean section require special consideration. We present a report of a
      parturient who presented at 36 weeks of gestation with severe aortic and mitral
      stenosis, pulmonary edema and severe preeclampsia. The goals of our anesthetic
      management included (1) careful airway management (2) maintaining stable
      hemodynamics (3) optimizing fluid status, and (4) preventing seizures. Issues
      related to management of patients with severe valvular disease, prosthetic valves
      and complications due to anticoagulant therapy during pregnancy are discussed.

PMID- 16798455
TI  - Spinal anaesthesia in a patient with hereditary spastic paraplegia: case report
      and literature review.
AB  - We report the use of spinal anaesthesia in a patient with hereditary spastic
      paraplegia who presented for manual removal of placenta following a normal
      vaginal delivery. This 18-year-old primigravida had been diagnosed with
      hereditary spastic paraplegia at 8 years of age when neurological examination
      revealed mild bilateral lower limb spasticity. A 25-gauge Whitacre spinal
      anaesthetic needle was inserted at the L3-4 intervertebral space and 0.5% plain
      bupivacaine 2 mL plus fentanyl 25 microg administered. The procedure was
      uneventful. At 24 hours postoperatively, there was full neurological recovery to
      pre-anaesthetic levels. The hereditary spastic paraplegias are a group of
      neurological disorders characterised by a slowly progressing spastic paraparesis.
      The neurological disorder and its anaesthetic implications are reviewed.

PMID- 16798456
TI  - The accidental use of 'inadvertent'.

PMID- 16798457
TI  - What is the standard of our aseptic technique?

PMID- 16798459
TI  - Hypotension and intraoperative nausea and vomiting during regional anesthesia for
      cesarean section.

PMID- 16798461
TI  - Tattoo or not to do?

PMID- 16798463
TI  - Allogeneic blood for epidural blood patch -- not without risk.

PMID- 16798464
TI  - Epidural blood patch with allogeneic blood for post-dural puncture headache.

PMID- 16798466
TI  - Solutions for patient-controlled epidural analgesia.

PMID- 16798468
TI  - Morbid obesity: a risk factor for maternal mortality.

PMID- 16798469
TI  - Anaphylactoid reaction to intravenous sodium ferric gluconate complex during
      pregnancy.

PMID- 16798470
TI  - Evaluation of pulmonary alveolo-capillary permeability in Type 2 diabetes
      mellitus: using technetium 99mTc-DTPA aerosol scintigraphy and carbon monoxide
      diffusion capacity.
AB  - The thickening of alveolar basement membrane is found in autopsies, along with
      microvascular pathologies, in Type 1 and 2 diabetes mellitus (DM). To detect the
      function and permeability of alveolar basement membrane, carbon monoxide
      diffusion capacity (DLCO) and technetium 99m-diethyltriaminepentaaceticacid
      ((99m)Tc-DTPA) aerosol scintigraphy methods can be used. The aim of this study
      was to determine alveolar basement membrane damage using these two methods.
      Nineteen women and 6 men, nonsmoking, Type 2 DM cases, without any lung and/or
      heart disease and who had neither anemia nor obesity, made up the patient group.
      They were compared with six female and nine male healthy cases who had the same
      characteristics with the diabetes cases. All of the cases DLCO were measured by
      single-breath method and (99m)Tc-DTPA aerosol scintigraphy was performed. DLCO
      showed no difference between the two groups. Aerosol scintigraphy was
      significantly decreased in the diabetic group (P=.01). In cases with >5 years of
      diabetic duration (P<.01), in cases with glycolized hemoglobin (HbA(1c)) </=8%
      (P<.05) and >8% (P<.05), and in microangiopathic cases (P<.01), alveolo-capillary
      permeability was significantly decreased than in the control group. Among the
      same groups, no significant difference could be detected for DLCO. The
      permeability of alveolar basement membrane can reduce in respect to diabetes
      duration and poor metabolic control. According to our investigation, (99m)Tc-DTPA
      aerosol scintigraphy method is more sensitive than DLCO method for determining
      these pathologies.

PMID- 16798471
TI  - Glomerular filtration rate changes in normoalbuminuric and microalbuminuric Type
      2 diabetic patients and normal individuals A 10-year follow-up.
AB  - AIM: To analyze the changes in the glomerular filtration rate (GFR) in a cohort
      of normoalbuminuric Type 2 diabetic (DM 2) patients and nondiabetic individuals.
      METHODS: Sixty-five normoalbuminuric DM 2 patients [urinary albumin excretion
      rate (UAER) <20 microg/min] and 44 nondiabetic individuals recruited at baseline
      were followed for a mean period of 10 +/- 1 years. In addition to conventional
      clinical and metabolic variables, GFR ((51)Cr-EDTA technique) and UAER
      (immunoturbidimetric method) measurements were performed at baseline and at
      follow-up. We also evaluated the presence of diabetic retinopathy, hypertension,
      and cardiovascular disease. Multiple linear regression was performed to assess
      variables independently associated with GFR evolution in patients with Type 2
      diabetes. RESULTS: Fifty DM 2 patients and 32 nondiabetic individuals were
      included in the follow-up evaluation. Fourteen out of the 50 patients with Type 2
      diabetes developed microalbuminuria. They presented a faster GFR decline (-0.39+/
      0.24 ml/min/month; ANOVA, P=.0013) than did persistently normoalbuminuric (
      0.16+/-0.16 ml/min/month) and nondiabetic individuals (-0.13+/-0.14
      ml/min/month). Multiple linear regression analysis disclosed baseline fasting
      plasma glucose (FPG) along with the development of microalbuminuria as factors
      significantly related to a higher GFR decline. CONCLUSIONS: Persistently
      normoalbuminuric patients and normal individuals presented a similar degree of
      GFR reduction related to the aging process. The slope was significantly enhanced
      in patients who developed microalbuminuria and was influenced by worse baseline
      glucose control.

PMID- 16798472
TI  - Exercise training can modify the natural history of diabetic peripheral
      neuropathy.
AB  - BACKGROUND: Diabetes is the most important cause of peripheral neuropathy (DPN).
      No definitive treatment for DPN has been established, and very few data on the
      role of exercise training on DPN have been reported. AIM OF THE STUDY: We sought
      to examine the effects of long-term exercise training on the development of DPN
      in both Types 1 and 2 diabetic patients. PARTICIPANTS AND METHODS: Seventy-eight
      diabetic patients without signs and symptoms of peripheral DPN were enrolled,
      randomized, and subdivided in two groups: 31 diabetic participants [15 f, 16 m;
      49+/-15.5 years old; body mass index (BMI)=27.9+/-4.7], who performed a
      prescribed and supervised 4 h/week brisk walking on a treadmill at 50% to 85% of
      the heart rate reserve (exercise group: EXE), and a control group of 47 diabetic
      participants (CON; 24 f, 23 m; 52.9+/-13.4 years old; BMI=30.9+/-8.4). Vibration
      perception threshold (VPT), nerve distal latency (DL), nerve conduction velocity
      (NCV), and nerve action potential amplitude (NAPA) in the lower limbs were
      measured. RESULTS: We found significant differences on Delta (delta) in NCV for
      both peroneal and sural motor nerve between the EXE and CON groups during the
      study period (P<.001, for both). The percentage of diabetic patients that
      developed motor neuropathy and sensory neuropathy during the 4 years of the study
      was significantly higher in the CON than the EXE group (17% vs. 0.0%, P<.05, and
      29.8% vs. 6.45%, P<.05, respectively). In addition, the percentage of diabetic
      patients who developed increased VPT (25 V) during the study was significantly
      higher in the CON than the EXE group (21.3% vs. 12.9%, P<.05). Change on Hallux
      VPT from baseline to the end of the study was significantly different between the
      EXE and CON groups (P<.05); no significant change in Malleolus VPT between the
      two groups occurred. CONCLUSIONS: This study suggests, for the first time, that
      long-term aerobic exercise training can prevent the onset or modify the natural
      history of DPN.

PMID- 16798473
TI  - Medical records as sources of data on cardiovascular disease events in persons
      with diabetes.
AB  - PURPOSE: The aim of this study is to evaluate medical records as a source of data
      on cardiovascular disease over a 20-year interval. METHODS: Participants in a
      population-based cohort of persons with Type 1 diabetes were asked whether they
      had been told by a doctor that they had several specific cardiovascular events.
      In addition, they were asked when and where they were hospitalized for myocardial
      infarction, stroke, surgical procedures, and for other conditions and procedures.
      The medical care institution was contacted to obtain copies of the relevant
      hospitalization. RESULTS: Overall, the confirmation of the self-reported events
      was 86.0% when medical records were obtained. Percent confirmed varied with the
      diagnosis. Reports of poor circulation in the lower extremities were confirmed in
      42.6%, stroke was confirmed in 70%, and coronary bypass surgery was confirmed in
      100% of cases. The success of obtaining medical records was greater for those
      events that were reported to have occurred more recently than those reported
      further in the past, especially when 10 or more years had elapsed. CONCLUSION:
      Medical record confirmation of reported cardiovascular events in persons with
      Type 1 diabetes was high for some events when medical records could be obtained
      but was lower for "poor circulation" to the legs and stroke possibly related to
      the lack of specificity of our questions, to incorrect attribution of symptoms by
      the respondent, or to inaccurate recall of a physician's examination. Medical
      record confirmation was better for more recent than past events. Therefore, when
      hard copy documentation is needed, it should be sought within 10 years of the
      event.

PMID- 16798474
TI  - Diabetic microvascular complications--can the presence of one predict the
      development of another?
AB  - The number of people with diabetes is increasing dramatically worldwide. The
      rising prevalence of obesity in childhood and adolescence has also been linked to
      a startling increase in the number of diagnosed cases of type 2 diabetes in these
      younger age groups. Despite the introduction of treatment strategies, diabetes
      remains a major cause of new-onset blindness, end-stage renal disease, and lower
      leg amputation, all of which contribute to the excess morbidity and mortality in
      people with diabetes. Furthermore, the management of diabetes-related
      complications generates substantial costs. In order that timely treatment can be
      given, it is essential that patients at risk for the development of diabetic
      microvascular complications are identified earlier. Diabetes duration and
      glycemic, blood pressure, and lipid control have consistently been shown to
      correlate with diabetic retinopathy, neuropathy, and nephropathy, but to date,
      the relationship of one diabetic microvascular complication to another has not
      been clearly described. A review of the literature has raised the question that
      apart from other known risk factors, there is a possible relationship among the
      diabetic microvascular complications themselves, and this appears to be much
      stronger than the sparse published data on it would suggest. A scoring system
      that can predict the development of diabetic microvascular complications may
      facilitate the early identification of those patients at risk and, consequently,
      have a positive impact on patients' quality of life and reduce the economic
      burden of diabetes and its complications.

PMID- 16798475
TI  - Diabetes and cognitive function in a population-based study of elderly women and
      men.
AB  - OBJECTIVES: The aim of this study was to examine the association between diabetes
      and cognitive function in the elderly. RESEARCH DESIGN AND METHODS: From January
      to December 2003, all 740 participants, aged 70 years or more, of an ongoing
      population-based cohort study were eligible for a telephone interview on
      cognitive function. Cognitive function was assessed using validated instruments,
      including the Telephone Interview of Cognitive Status (TICS) and the East Boston
      Memory Test (EBMT). Information on diabetes was available from prior
      questionnaires and was validated in 2002. We used multivariable logistic
      regression to estimate odds ratios (OR) of an impaired cognitive function (below
      25th percentile) and their 95% confidence intervals (CI) adjusting for age,
      gender, smoking, alcohol consumption, body mass index (BMI), physical exercise,
      educational level, and depressive symptoms. RESULTS: Out of 473 participants
      interviewed (64.9%), 66 had diabetes (14.1%). The adjusted OR for diabetes and
      impaired cognitive function assessed by TICS was 2.3 (95% CI: 1.2-4.3). Diabetes
      was also associated with performance on delayed recall EBMT (adjusted OR=2.0; 95%
      CI: 1.0-4.1), but not immediate EBMT recall (adjusted OR=1.0; 95% CI: 0.5-2.1).
      The association between diabetes and cognitive function was a bit more pronounced
      in participants in whom diabetes was diagnosed 12 (median) or more years prior
      (adjusted OR with TICS=2.4; 95% CI: 1.0-5.8) and in those without antidiabetic
      treatment (age- and sex-adjusted OR=3.4; 95% CI: 1.7-6.5). CONCLUSION: Diabetes
      should be considered to be a risk factor for cognitive impairment in the elderly,
      which might be attenuated by antidiabetic treatment.

PMID- 16798476
TI  - Posterior subtenon and intravitreal triamcinolone acetonide for diabetic macular
      edema.
AB  - AIM: To evaluate retroprospectively the clinical consequences of posterior
      subtenon (PSTT) and intravitreal (IVT) triamcinolone acetonide injections in
      diabetic macular edema (DME) refractory to conventional grid laser
      photocoagulation. MATERIAL AND METHODS: Eyes with clinically significant DME
      refractory to grid laser photocoagulation were assessed for the inclusion in the
      study. Complete ophthalmic examination with fluorescein angiography (FA) and
      optic coherence tomography (OCT) were performed before and in the 1st, 3rd, and
      6th months of the treatment. The IVT group received 4 mg/0.1 ml and the PSTT
      group received 20 mg/0.5 ml triamcinolone injection. PSTT but not IVT injection
      was repeated in case of recurrent edema. IVT was also applied to the eyes with
      resistant macular edema after PSTT injection (secondary IVT group). RESULTS:
      There were 85 eyes of 60 patients in the PSTT group and 41 eyes of 35 patients in
      IVT group. There were 24 eyes in the primary IVT group and 17 eyes in the
      secondary IVT group. Mean follow-up time was 4.1+/-1.9 and 4.6+/-2.2 months after
      PSTT and IVT injections, respectively. In the PSTT group, the mean visual acuity
      increased from 0.19+/-0.18 to 0.22+/-0.19 and the mean central foveal thickness
      decreased from 413.1+/-117.5 to 312.1+/-103.1 microm (P=.001 and P=.0001,
      respectively) during the first 3 months. In the IVT group, the mean visual acuity
      and central foveal thickness were found to be 0.15+/-0.14 and 494.5+/-141.3
      microm before the treatment and 0.20+/-0.16 and 288.4+/-88.5 microm 3 months
      after the treatment, respectively (P=.008 and P=.001, respectively). The effect
      in central foveal thickness was significantly greater in the primary IVT group
      than in the PSTT group (P=.002). There was no significant difference with respect
      to the decrease in the central foveal thickness and increase in visual acuity
      between the primary and secondary IVT injections (Mann-Whitney U test, P>.05).
      The steroid effect started to diminish after the 3rd month. The recurrence of
      macular edema was seen in 7.1% in the PSTT group starting after 3 months. Twenty
      percent of the eyes in the PSTT group did not respond to the treatment at all and
      had secondary IVT injections. Significant intraocular pressure increase was found
      in 8.2% of the PSTT group and in 24.3% of IVT injection. There was one case of
      pseudomonas endophthalmitis in the IVT group. CONCLUSION: This study is the first
      study comparing the clinical outcomes of PSTT and IVT injections for the
      treatment of DME. Both PSTT and IVT injections caused a significant increase in
      visual acuity and a decrease in central foveal thickness, especially in the short
      term. The effect was more pronounced in the IVT group; however, PSTT injection
      also seemed to be a safe and effective technique for the treatment of DME.
      Further prospective studies are warranted to assess the efficacy and side effects
      of IVT and PSTT injections for the treatment of DME.

PMID- 16798477
TI  - Growth, puberty, and final height in children with Type 1 diabetes.
AB  - OBJECTIVE: The aims of this study were to assess the physical growth and pubertal
      development in a group of diabetic children and to evaluate the effect of height
      at diagnosis, duration of illness, and degree of glycemic control on final height
      and sexual maturation. RESEARCH DESIGN: A cohort of 72 Sudanese diabetic
      children, 7-13 years of age at diagnosis, was followed longitudinally from the
      onset of diabetes until the attainment of final height. RESULTS: The mean height
      standard deviation scores (SDS) at diagnosis were 0.04 in boys and -0.15 in
      girls, which was greater than their genetic target height (GTH). The growth
      velocity between diagnosis and final height was slow, with significant reduction
      in pubertal growth spurt. The mean final height attained by these children was
      lower than their GTH, a finding that contradicts most of the recently published
      reports. The average age at menarche in girls (15.1 years) and the mean age of
      full sexual maturation in boys (17.2 years) were significantly delayed in this
      group of diabetic patients. This retardation in physical growth and pubertal
      development was positively correlated with the duration of diabetes before the
      onset of puberty and glycated haemoglobin (HbA1c) concentration. The majority of
      these patients were thin at diagnosis of diabetes, with median body mass index
      (BMI) <22, but showed a remarkable, progressive weight gain during puberty, which
      was more evident in girls. The weight gain was independent of weight at diagnosis
      and duration of diabetes, but was positively correlated with the daily dose of
      insulin and HbA1c concentration. CONCLUSION: Conventional therapy of diabetic
      children is associated with impairment of physical growth and delayed sexual
      maturation.

PMID- 16798478
TI  - Heat shock protein 60 response to exercise in diabetes: effects of alpha-lipoic
      acid supplementation.
AB  - The pathophysiology of diabetes includes oxidative stress and impaired heat shock
      protein (HSP) expression. We studied the effects of alpha-lipoic acid (LA)
      supplementation for 8 weeks and acute exercise on HSP60 expression and the
      oxidative stress marker 4-hydroxynonenal adducts (4-HNE) in streptozotocin
      induced diabetic (SID) and nondiabetic control rats. Diabetes was associated with
      decreased HSP60 in the heart and increased levels of HSP60 and 4-HNE in the
      liver. LA increased HSP60 in the liver of control and diabetic rats and decreased
      4-HNE in the liver and heart. Acute exercise increased liver 4-HNE, which was
      offset by LA. In conclusion, diabetes induced oxidative stress and impaired
      myocardial HSP60 expression, while LA partially offsets these alterations in a
      tissue-specific manner.

PMID- 16798479
TI  - Anemia and the role of erythropoietin in diabetes.
AB  - Anemia is more common in patients with diabetes than without diabetes, and the
      problem is magnified in patients with renal impairment. Diabetic patients with
      anemia may be at increased risk of adverse outcomes from diabetic retinopathy,
      nephropathy, neuropathy, and cardiovascular disease. The etiology of anemia in
      diabetes is multifactorial and includes inflammation, nutritional deficiencies,
      concomitant autoimmune diseases, drugs, and hormonal changes in addition to
      kidney disease. Anemia that is associated with erythropoietin deficiency may have
      prognostic significance for persons with nephropathy or heart failure. In early
      diabetic nephropathy, damage to the peritubular fibroblasts can occur and lead to
      erythropoietin deficiency and anemia prior to the loss of filtration. Correction
      of the anemia not only leads to less fatigue, greater exercise tolerance, and an
      improved quality of life but also to a reduction in mortality and hospital
      admissions for congestive heart failure (CHF). Data are accumulating that suggest
      that treatment of anemia will slow the progression of microvascular and
      macrovascular complications, including postural hypotension from autonomic
      neuropathy, retinopathy, and loss of renal function from diabetic nephropathy.
      Promptly diagnosing and treating anemia in patients with diabetes may result in
      an improved quality of life and decreased morbidity and mortality.

PMID- 16798481
TI  - Intraoperative parathyroid hormone measurement during minimally invasive
      parathyroidectomy: does it "value-add" to decision-making?
AB  - BACKGROUND: Routine use of intraoperative parathyroid hormone levels (IOPTH)
      during minimally invasive parathyroidectomy (MIP) has been challenged simply
      because the test works best when needed least, ie, once a solitary adenoma has
      been resected, and is less accurate with multiple gland disease. It has also been
      shown not to be cost-effective. The aim of this study was to determine if IOPTH
      "value-added" to decision-making during MIP. STUDY DESIGN: The study group
      comprised 100 consecutive patients with sporadic hyperparathyroidism and an
      unequivocally positive sestamibi scan who were undergoing MIP in our unit from
      June 2004 until October 2005, from whom blood was collected for parathyroid
      hormone measurement preoperatively, preexcision, and at 10 and 30 minutes
      postremoval. No action was taken on the results of the test. RESULTS: Ninety
      eight patients were cured by MIP alone. Two patients had persistent
      hyperparathyroidism, one of whom was cured with subsequent open reexploration and
      removal of a second adenoma, and the other remains hypercalcemic despite
      additional open neck exploration. IOPTH in both patients failed to fall in
      retrospect, only the first would have been cured by conversion at the time of
      operation. The value-added accuracy of IOPTH was really only 1%. In an additional
      nine patients, IOPTH at 10 minutes had failed to fall by > 50% from the highest
      level, those patients (9%) would have been subjected to an unnecessary conversion
      on the basis of a false-negative result. CONCLUSIONS: IOPTH does not
      substantially value-add to decision-making during MIP. Most patients will be
      cured with appropriate selection for MIP based on preoperative localization
      studies.

PMID- 16798482
TI  - Minimally invasive esophagectomy: thoracoscopic mobilization of the esophagus and
      mediastinal lymphadenectomy in prone position--experience of 130 patients.
AB  - BACKGROUND: To evaluate outcomes after minimally invasive or thoracolaparoscopic
      esophagectomy (TLE) with thoracoscopic mobilization of the esophagus and
      mediastinal esophagectomy in prone position. Esophagectomies are being performed
      increasingly by a minimally invasive route with decreased morbidity and shorter
      hospital stay compared with conventional esophagectomy. Most series report
      thoracoscopic mobilization of the esophagus and mediastinal lymphadenectomy in
      the left lateral position with respiratory complications up to 8% and prolonged
      operative time, probably because of inadequate stance of the surgeon during the
      thoracoscopic part. This study shows the potential of the thoracoscopic part of
      the procedure in prone position to ease these difficulties. STUDY DESIGN: From
      January 1997 through April 2005, TLE was performed in 130 patients. All patients
      had histologically proved squamous cell carcinoma of the middle third of the
      esophagus. Only one (0.77%) patient received neoadjuvant chemotherapy. The
      thoracoscopic part of the procedure was performed in prone position with
      excellent ergonomics, translating into less operative time and better respiratory
      results. We performed a minilaparotomy to retrieve the specimen owing to bulky
      tumors. Feeding jejunostomy and pyloromyotomy were performed in all patients.
      RESULTS: There were 102 men and 28 women. Median age was 67.5 years (range 38 to
      78 years). There was no conversion to open method. Median ICU stay was 1 day
      (range 1 to 32 days) and median hospital stay was 8 days (range 4 to 68 days).
      Perioperative mortality was 1.54% (n = 2). Anastomotic leak rate was 2.31% (n =
      3). There was no incidence of tracheal or lung injury and a very low incidence of
      postoperative pneumonia. At mean followup of 20 months (range 2 to 70 months),
      stage-specific survival was similar to open and other minimally invasive series.
      CONCLUSIONS: TLE with thoracoscopic part in prone position is technically
      feasible, with a low incidence of respiratory complications and less operative
      time required. It provides comparable outcomes with other techniques of minimally
      invasive esophagectomy and most open series. In our experience, we observed a low
      mortality rate (1.54%), hospital stay of 8 days, and low incidence of
      postoperative pneumonia. It has the potential to replace conventional and other
      techniques of minimally invasive esophagectomy.

PMID- 16798483
TI  - Inguinal hernia repair protects testicular function: a prospective study of open
      and laparoscopic herniorraphy.
AB  - BACKGROUND: Despite the frequency of open and laparoscopic herniorraphy the
      effect of the hernia and subsequent repair on testicular function is unknown. Our
      objective was to determine if there is an association between inguinal hernia and
      hernia repair on testicular function. STUDY DESIGN: Thirty-seven men aged 18 to
      70 years were enrolled in a prospective internally controlled cohort study. They
      underwent Doppler ultrasonography and serum testicular hormone analysis pre- and
      post- either open Lichtenstein's repair or laparoscopic totally extraperitoneal
      hernioplasty. These surrogates of testicular function were measured up to 6
      months postrepair. RESULTS: Thirty-seven consecutive patients underwent either
      Lichtenstein (n = 17) or totally extraperitoneal hernioplasty (n = 20) hernia
      repair as per surgeon preference. Preoperatively there was a significant
      elevation in the sonographic resistive index (RI) in the affected (hernia) side
      compared with the normal side (0.601, 0.569; p < 0.001). This elevation in RI was
      reversed posthernia repair at a median followup of 6.1 months. Inguinal hernia or
      repair did not affect testicular volume. The choice of either Lichtenstein or
      totally extraperitoneal hernioplasty hernia did not significantly alter the
      testicular function. CONCLUSIONS: Patients with inguinal hernia have an elevated
      testicular vascular resistance, which is reversed after repair. The choice of
      laparoscopic or open herniorraphy did not affect reversal of this surrogate of
      testicular function.

PMID- 16798484
TI  - Resolution of hyperlipidemia after laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Hyperlipidemia is an established risk factor for development of
      coronary artery disease. The aim of our study was to examine the changes in serum
      lipid profiles of morbidly obese patients complicated by hyperlipidemia, who
      underwent laparoscopic gastric bypass. STUDY DESIGN: We retrospectively reviewed
      the charts of 95 morbidly obese patients with documented hyperlipidemia who
      underwent laparoscopic gastric bypass. Mean duration of hyperlipidemia was 44+/-
      56 months. Hyperlipidemia was defined as an elevated level of triglycerides (>
      150 mg/dL) or total cholesterol (> 200 mg/dL). Changes in lipid profile of a
      subset of patients with subnormal levels of high-density lipoprotein cholesterol
      (<or= 40 mg/dL), high levels of low-density lipoprotein cholesterol (> 130
      mg/dL), and very-low-density lipoprotein cholesterol (> 40 mg/dL) were also
      examined. Fasting lipid profiles were measured preoperatively and at 3-month
      intervals. RESULTS: There were 68 women (72%) with a mean age of 43 +/- 10 years.
      Mean body mass index was 47+/- 5 kg/m2. Mean percentage of excess body weight
      loss at 12 months postoperatively was 66%. One year after gastric bypass, mean
      total cholesterol levels decreased by 16%; triglyceride levels decreased by 63%;
      low-density lipoprotein cholesterol levels decreased by 31%; very-low-density
      lipoprotein cholesterol decreased by 74%; total cholesterol/high-density
      lipoprotein cholesterol risk ratio decreased by 60%, and high-density lipoprotein
      cholesterol levels increased by 39%. Also, within 1 year, 23 of 28 (82%) patients
      requiring lipid-lowering medications preoperatively were able to discontinue
      their medications. CONCLUSIONS: Weight loss after laparoscopic gastric bypass
      substantially improves lipid profiles in morbidly obese patients who have
      hyperlipidemia. Improvement in lipid profiles was observed as early as 3 months
      postoperatively and was sustained at 1 year. Improvement of lipid profiles after
      laparoscopic gastric bypass can reduce health risks associated with high levels
      of atherogenic lipoproteins.

PMID- 16798485
TI  - Auditing 655 fatalities with pelvic fractures by autopsy as a basis to evaluate
      trauma care.
AB  - BACKGROUND: To determine the role of pelvic fractures in auditing mortality
      resulting from trauma. STUDY DESIGN: This retrospective case-control study based
      on autopsy-evaluated circumstances of the deaths of patients with pelvic
      fractures. RESULTS: Of 2,583 patients injured in motor-vehicle collisions, 655
      (25.4%) constituted the pelvic fracture (PFx) group, and 1,928 (74.6%)
      constituted the control group. One-third of the PFx group's fatalities had an
      Injury Severity Score (ISS) of 75 and were not preventable. The PFx group had a
      substantially higher median ISS than the control group (50 versus 34; p <
      0.0001). Four hundred fifty-four patients (69.3%) in the PFx group with ISS 16 to
      74 had substantially higher rates of associated injuries. Nearly half of the PFx
      group patients with ISS <or= 74 had a potential cause of major hemorrhage other
      than pelvic fracture. Twenty-three (3.5%) deaths were directly attributable to
      pelvic fractures. Postinjury median survival time was 55 minutes for the PFx
      group and 100 minutes for the control group (p < 0.0001). The time limit for
      management of the patients with pelvic fractures was short, as 527 (81.5%) died
      in the first 6 hours. It was evident that the more severe the injuries were, the
      sooner the deaths occurred. Of 151 subjects who left the emergency department
      alive, 61.6% were subjected to operation and 48.3% to abdominal operation.
      CONCLUSIONS: Pelvic fracture is an indicator of severe multiple trauma, but a
      small proportion of deaths are directly attributable to pelvic fracture. A method
      based on autopsy audited patients with pelvic fractures as a paradigm of injury
      revealed that pelvic fracture is an important injury to consider in auditing
      trauma care and indicated several issues that should be considered to reduce
      mortality.

PMID- 16798486
TI  - Poly adenosine diphosphate-ribose polymerase inhibitor PJ34 abolishes systemic
      proinflammatory responses to thoracic aortic ischemia and reperfusion.
AB  - BACKGROUND: Systemic inflammatory responses contribute to mortality after
      thoracoabdominal aneurysm repair. Poly adenosine diphosphate (ADP) ribose
      polymerase (PARP) activity is known to modulate inflammation in animal models of
      injury. The effect of the PARP inhibitor PJ34 and genetic deletion of PARP-1(PARP
      -/-) on the systemic inflammatory response after thoracic aortic ischemia
      reperfusion (TAR) is not known. STUDY DESIGN: In one group, all mice were subject
      to TAR followed by 48 hours of reperfusion. Treated mice (PJ, n=24) were given
      PJ34 IP; untreated mice (UN, n=41) received normal saline intraperitoneally. The
      number of mice in each group was selected to have a similar number of survivors
      by 48 hours. In a second group, sham animals were subjected to mediastinotomy
      alone (sham, n=10) without TAR, and were compared with mice with deletion of the
      PARP-1 isoform (PARP-1 -/-, n=11) subjected to TAR. Tissue extracts were assayed
      for keratinocyte derived chemokine and granulocyte colony stimulating factor.
      Serum was assayed for interleukin-6. RESULTS: PJ34 treatment decreased mortality
      throughout the experimental protocol. There were no mortalities in the sham
      operated mice or PARP -/- mice subjected to TAR. PJ34 treatment decreased serum
      levels of interleukin-6 (p=0.01) and hepatic levels of interleukin-6 mRNA when
      compared with untreated and PARP-/- mice (p < 0.01). Only liver and kidney
      cytokine levels were decreased by PJ34 treatment (p < 0.05). In PARP-/- mice
      subjected to TAR, tissue cytokine levels were not different from those in sham
      mice. CONCLUSIONS: PARP inhibition may represent a novel therapeutic approach to
      minimizing inflammatory sequelae after TAR.

PMID- 16798487
TI  - Magnetic resonance-guided focused ultrasound surgery of breast cancer:
      reliability and effectiveness.
AB  - BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a
      noninvasive technique that has been shown to coagulate benign and malignant
      tumors. The purpose of this study was to evaluate MRgFUS safety and effectiveness
      for the ablation of breast carcinomas. STUDY DESIGN: Thirty women with biopsy
      proved breast cancer underwent MRgFUS treatment. Gadolinium-enhanced MR images
      were used for treatment planning and posttreatment radiologic assessment of
      treated tissue, and temperature-sensitive MR images provided real-time treatment
      monitoring. After MRgFUS, all 30 women underwent wide excision or mastectomy. The
      extent of thermal ablation was assessed with tumor histology. RESULTS: Treatment
      was well tolerated, with a minimum of adverse effects, especially when performed
      under local anesthesia. On pathologic examination, mean (+/-SD) necrosis of the
      targeted breast tumors was 96.9 +/- 4% (median 100%, range 78% to 100%) of tumor
      volume. Fifteen (53.5%) of 28 evaluable patients had 100% necrosis of the ablated
      tumor; only 3 patients (10.7%) had less than 95% necrosis. In 28 (93.3%)
      patients, 100% of the malignancy was within the treatment field, and 98% and 95%
      of tumor lay within the treatment field in 2 remaining patients. Retrospective
      analysis in two patients with residual tumor showed treatment was not delivered
      to the full recommended area, reaffirming the need for precise localization and
      the value of contrast-enhanced images for treatment planning. CONCLUSIONS: MRgFUS
      has great potential to become a viable noninvasive replacement for lumpectomy.
      Additional studies focusing on posttreatment image-based evaluation are needed.

PMID- 16798488
TI  - Use of lymphoscintigraphy defines lymphatic drainage patterns before sentinel
      lymph node biopsy for breast cancer.
AB  - BACKGROUND: Lymphoscintigraphy (LSG) can identify lymphatic drainage patterns
      before sentinel lymph node (SLN) biopsy is performed in patients with early-stage
      breast cancer, but the importance of extraaxillary SLNs seen on LSG is unknown.
      We assessed whether drainage patterns seen on LSG were associated with histologic
      findings in axillary SLNs recovered at SLN biopsy. STUDY DESIGN: From a
      prospectively maintained database, we identified 1,201 clinically node-negative
      patients with invasive breast cancer who underwent preoperative LSG and axillary
      SLN biopsy. Patient and tumor characteristics, LSG results, and final SLN
      pathology results were examined. RESULTS: LSG showed drainage to internal mammary
      (IM) nodes in 1.6% of patients, axillary nodes in 68.1%, both IM and axillary
      nodes in 19.8%, and no drainage in 10.3%. Drainage to IM nodes was observed for
      tumors in all quadrants of the breast. Patients with IM drainage had a younger
      median age than patients without IM drainage (51.8 versus 58.3 years,
      respectively; p < 0.001). The intraoperative axillary SLN identification rate was
      higher when axillary drainage was observed on LSG than when it was not observed
      (98.7% versus 93.0%, respectively; p < 0.001), but the LSG drainage pattern was
      not associated with pathologic status of the SLN or number of metastatic SLNs. At
      a median followup of 32 months, 4 patients had regional nodal recurrence.
      CONCLUSIONS: Almost one-fourth of patients had lymphatic drainage to the
      extraaxillary lymph nodes, particularly the IM nodes, seen on LSG. Extraaxillary
      drainage seen on LSG did not preclude identification of axillary SLNs at
      operation. Longterm followup of patients with lymphoscintigraphic evidence of
      extraaxillary drainage is needed to determine whether regional and systemic
      recurrence patterns differ in these patients.

PMID- 16798489
TI  - Monocyte HLA-DR and interferon-gamma treatment in severely injured patients--a
      critical reappraisal more than a decade later.

PMID- 16798490
TI  - Body contouring in the postbariatric surgery patient.

PMID- 16798492
TI  - Impact and implications of disruptive behavior in the perioperative arena.
AB  - BACKGROUND: There is a growing concern about the role of human factor issues and
      their effect on patient safety and clinical outcomes of care. Problems with
      disruptive behaviors negatively affect communication flow and team dynamics,
      which can lead to adverse events and poor quality outcomes. STUDY DESIGN: A 25
      question survey tool was used to assess the status and significance of disruptive
      behaviors around perioperative services in a large metropolitan academic medical
      center. Results were analyzed and compared with those from a national databank to
      identify areas of concern and opportunities for improvement. RESULTS: Disruptive
      behaviors were a common occurrence in the perioperative setting. These types of
      behaviors were most prevalent in attending surgeons. Disruptive behaviors
      increased levels of stress and frustration, which impaired concentration, impeded
      communication flow, and adversely affected staff relationships and team
      collaboration. These events were perceived to increase the likelihood of medical
      errors and adverse events and to compromise patient safety and quality of care.
      CONCLUSIONS: Disruptive behaviors in the perioperative arena have a significant
      impact on team dynamics and communication flow, which can have a negative impact
      on patient care. Organizations need to recognize the prevalence and significance
      of disruptive behaviors and develop policies and processes to address the issue.
      Key areas of focus include recognition and awareness, organizational and cultural
      commitment, implementation of appropriate codes of behavior policies and
      procedures, and provision of education and training programs to discuss
      contributing factors and tools to build effective communication and team
      collaboration skills.

PMID- 16798493
TI  - A balanced approach to tourniquet use: lessons learned and relearned.

PMID- 16798494
TI  - Arpad G Gerster, MD, and the first photographic surgical textbook.

PMID- 16798495
TI  - Spontaneous splenic rupture in a patient with bacterial endocarditis.

PMID- 16798496
TI  - Portosystemic gas related to splenic abscess from penetrating colon cancer.

PMID- 16798497
TI  - Initial report of laparoscopic celiac plexus block for pain relief in patients
      with unresectable pancreatic cancer.

PMID- 16798498
TI  - A simple technique to remove a large object from the rectum.

PMID- 16798499
TI  - Acute postoperative frailty.

PMID- 16798500
TI  - Level IV neck dissection in laryngeal carcinoma.

PMID- 16798503
TI  - Detailed investigation of the relationship between the inferior laryngeal nerve,
      including laryngeal branches and ligament of berry.

PMID- 16798504
TI  - Antibiotic prophylaxis for hernia repair.

PMID- 16798505
TI  - Economic evaluation of minimally invasive colectomy.

PMID- 16798506
TI  - Importance of registering clinical trials.

PMID- 16798507
TI  - "The missing thyroid:" fact or fallacy?

PMID- 16798511
TI  - Ankle anatomy for the arthroscopist. Part I: The portals.
AB  - Proper portal placement is critical to performing good diagnostic and therapeutic
      arthroscopy. When the portals are positioned improperly, visualization can be
      impaired, making diagnosis and treatment more difficult. Three main anterior
      portals are available in arthroscopy of the ankle: anteromedial, anterolateral,
      and anterocentral. Posterior portals are also routinely used in ankle arthroscopy
      and can be established at a posterolateral or posteromedial position or directly
      through the Achilles tendon. Because of the potential for serious complications,
      the anterocentral and transAchilles portals are no longer used. Other portals
      have been described to obtain more complete access, particularly to the posterior
      compartment of the ankle joint. This work reviews the relationships that exist
      between the most important anatomic structures and arthroscopic portals of the
      ankle.

PMID- 16798512
TI  - Ankle anatomy for the arthroscopist. Part II: Role of the ankle ligaments in soft
      tissue impingement.
AB  - The biomechanical anatomy of the ankle ligaments continues to be a subject of
      interest because detailed knowledge of these structures is essential for proper
      diagnosis and treatment of the injuries affecting them. Lesions to the ankle
      ligaments are one of the most common sports injuries and the origin of soft
      tissue impingement syndrome. Together with the ligaments of the tibiofibular
      syndesmosis, two large ligamentous complexes are the main static stabilizers of
      the ankle joint: the lateral collateral ligament and the medial collateral (or
      deltoid) ligament. This article provides an anatomic description of the various
      ligaments of the ankle joint, with particular emphasis on specific anatomic
      details that are often omitted or little known and that have considerable
      clinical interest because of their involvement in soft tissue syndrome.

PMID- 16798513
TI  - Anterior ankle impingement.
AB  - The anterior ankle impingement syndrome is a clinical pain syndrome that is
      characterized by anterior ankle pain on (hyper) dorsiflexion. The plain
      radiographs often are negative in patients who have anteromedial impingement. An
      oblique view is recommended in these patients. Arthroscopic excision of soft
      tissue overgrowths and osteophytes is an effective way of treating anterior
      impingement of the ankle in patients who have no narrowing of the joint space.
      For grade II lesions (osteophytes secondary to arthritis with joint space
      narrowing) arthroscopic treatment is a good option, because no other therapeutic
      option is available with the exception of an arthrodesis or prothesis.

PMID- 16798514
TI  - Ankle instability.
AB  - The ankle joint is the most congruent joint of the human body. Stability is
      provided by the bony configuration of the ankle mortise and the talar dome and by
      the ankle ligaments. During ankle motions, rotation and translation around and
      along the movement axes occur. Soft tissue stability is provided mainly by the
      ligaments. This article discusses ankle instability, injuries, and
      reconstruction.

PMID- 16798515
TI  - Current concepts: treatment of osteochondral ankle defects.
AB  - Osteochondral ankle defects cause various symptoms including pain, swelling, and
      limited range of motion. When surgical treatment is necessary, several treatment
      options exist. Arthroscopic debridement and drilling, arthroscopic autologous
      osteochondral transplantation (mosaiclasty), and autologous chondrocyte
      transplantation are discussed more extensively. Treatment results of each
      technique are discussed, and a guideline for treatment is presented.

PMID- 16798516
TI  - Arthroscopic ankle arthrodesis.
AB  - Surgical options are limited for the patient who has symptomatic severe ankle
      joint degeneration that is unresponsive to nonoperative treatment. Arthrodesis of
      the tibiotalar joint is a procedure that can produce a pain-free ankle that can
      withstand the rigors of daily life, even in a young, high-demand, working
      individual. Minimally invasive orthopedic techniques have been applied to ankle
      arthrodesis, and arthroscopic ankle fusion has been shown to be an effective
      technique to achieve tibiotalar arthrodesis, with high rates of fusion and low
      rates of complication. This article covers indications, contraindications, and
      procedural techniques for arthroscopic ankle arthrodesis. Results of arthroscopic
      versus open ankle arthrodesis are compared.

PMID- 16798517
TI  - Arthroscopy of the posterior subtalar joint.
AB  - The subtalar joint is a complex and functionally important joint of the lower
      extremity. It plays a major role in the movement of inversion and eversion of the
      foot. With the development of small-joint arthroscopes and instrumentation,
      surgeons became interested in posterior subtalar joint arthroscopy. Diagnostic
      and therapeutic indications for this technique have increased; however,
      arthroscopic subtalar surgery is technically difficult and should be performed by
      an experienced arthroscopist. The number of reports dealing with posterior
      subtalar arthroscopy remains relatively small.

PMID- 16798518
TI  - Hindfoot endoscopy.
AB  - Hindfoot pain can be caused by a variety of pathologies; most of these can be
      diagnosed and treated by means of endoscopy. The main indications are posterior
      tibial tenosynovectomy, diagnosis of a peroneus brevis length rupture, peroneal
      tendon athesiolysis, flexor hallucis longus release, os trigonum removal,
      endoscopic treatment for retrocalcaneal bursitis, endoscopic treatment for
      Achilles (peri)tendinopathy, and treatment of ankle joint or subtalar joint
      pathology. The advantages of endoscopic hindfoot surgery over open surgery are
      less morbidity, reduction of postoperative pain, outpatient treatment, and
      functional postoperative treatment. This two-portal hindfoot endoscopy approach
      is a safe, reliable, and exciting method to diagnose and treat a variety of
      posterior ankle problems and offers a good alternative to open surgery.

PMID- 16798519
TI  - Tendoscopy of the peroneal tendons.
AB  - Tendoscopy of the peroneal tendons is a useful tool to diagnose and treat
      peroneal tendon disorders. Endoscopic ankle surgery is followed by a functional
      postoperative treatment and offers the advantages of less morbidity, reduction of
      postoperative pain, and outpatient surgery. The article describes the technique
      and results of peroneal tendoscopy performed in 23 patients between 1995 and
      2000.

PMID- 16798520
TI  - Tendoscopy of the posterior tibial tendon.
AB  - Posteromedial ankle complaints are most often caused by a disorder of the
      posterior tibial tendon. Two predominant groups of patients can be distinguished:
      the first involves younger patients who have some form of systemic inflammatory
      disease; the second involves older patients whose dysfunction is caused by
      chronic overuse. This article illustrates endoscopy of the posterior tibial
      tendon in a group of patients who had diverse pathology. None of the patients
      showed postoperative complications. All showed a quick recovery, early
      mobilization, none or mild postoperative pain, and nice wound healing. Although
      not all patients were free of complaints, all were satisfied with the
      intervention itself. Tendoscopy of the poterior tibial tendon offers the
      advantage of less morbidity, reduction of the postoperative pain, early
      mobilization, no wound healing problems and outpatient treatment.

PMID- 16798521
TI  - Achilles tendoscopy.
AB  - Noninsertional Achilles tendon-related problems can be treated well by an
      endoscopic approach if they do not respond to nonoperative management.
      Understanding the anatomy and the mechanical aspects of the hindfoot and having
      experience with endoscopic procedures are necessary. A retrospective study of 20
      patients showed good results.

PMID- 16798522
TI  - Endoscopic calcaneoplasty.
AB  - This article describes the technique of endoscopic calcaneoplasty and the results
      of a consecutive group of patients that was treated in the prone position in the
      authors' hospital.

PMID- 16798524
TI  - Current pharmacological treatments for bronchiolitis are useless. The case for
      the con's.
AB  - Bronchiolitis is a recognized syndrome seen in infants following viral
      infections. The pattern is different in different countries related to the socio
      economic conditions. A sequel that needs to be addressed is post-viral wheeze.
      Oxygen is the major beneficial pharmacological agent. Bronchodilators may be
      effective in some. There is a role for Palivizumab and Montelukast in selected
      infants. It is essential to define the right drug for the right patient at the
      right dose and the right time.

PMID- 16798525
TI  - Novel molecular therapy.
AB  - Anti-inflammatory treatment, mainly with inhaled corticosteroids, is the
      cornerstone of asthma therapy. There are a number of new more specific therapies
      based on a molecular approach. Despite some promising results from some novel
      molecular therapies there are also some studies which have shown no effect of
      these treatments.

PMID- 16798526
TI  - Immunotherapy as a disease modifier.
AB  - Immunotherapy was formerly the treatment of allergic disease by repeated exposure
      to allergen. Other approaches to immune modulation have emerged using new
      knowledge of T cell function. The so-called hygiene hypothesis argues that
      alterations in our environment have resulted in a failure of the immune system to
      develop normally, such that excessive Th2 type responses to antigen exposures
      occur. These observations have prompted therapies designed to promote a shift
      from Th-2 to Th-1 responses. These therapies include bacterial vaccines and
      stimulation of the immune system with Toll like receptor ligands or bacterial
      nucleotide immunostimulatory sequences (CpG motifs). Traditional desensitization
      immunotherapy is being re-examined and anti-IgE therapy is also enjoying a
      measure of success.

PMID- 16798527
TI  - Can we treat airway remodeling?
AB  - Asthma is a chronic disease that has been associated with structural changes of
      the airway wall. These changes lead to decreased reversibility of airway
      obstruction and have been understood as poorly reversible. Recent studies have
      proved that even some of the processes involved in airway remodeling may be
      reversible with early detection of the disease and appropriate anti inflammatory
      treatment. New treatments should be directed not only against inflammation itself
      but also against these chronic changes.

PMID- 16798528
TI  - Spirometry.
AB  - Recent data indicate that clinicians and researchers should dismiss the myth that
      preschoolers are unable to perform spirometry. Reproducible, acceptable flow
      volume curves are possible in this age group; however, modifications to the
      ATS/ERS adult criteria are critical due to physiologic differences. Reference
      data is available and the clinical applicability of this technique is being
      evaluated.

PMID- 16798529
TI  - Is hygiene damaging to your health?

PMID- 16798530
TI  - Pre-school wheeze: how do we treat and how do we monitor treatment?

PMID- 16798531
TI  - Preschool wheeze prognosis: how do we predict outcome?
AB  - Preschool wheezing is extremely common. Despite its prevalence, prognosis is
      often hard to determine. Preschool wheezing is not without significant associated
      morbidity which may result in increased utilization of medical resources. The
      child with preschool wheezing may represent one of at least three distinct
      phenotypes, each having different clinical significance and therapeutic
      implications. The challenge to the clinician is to correctly identify the
      operative phenotype as a basis for family education, effective therapy and
      ultimately a reasonable assertion regarding prognosis. The current article
      reviews clinical presentation, potential etiologies and triggers as well as
      historical, hereditary and laboratory markers that may aid in the diagnosis and
      management of this challenging presentation among preschool children.

PMID- 16798532
TI  - Asthma in urban setting: a southern American perspective.
AB  - To manage asthma in urban setting of developing countries is a challenge to the
      health system of developing countries. To reduce asthma morbidity (hospital
      admissions and emergency visits) is the main goal to be reached. It is necessary
      to adapt international guidelines considering the local constraints. The
      provision of free medication is mandatory. Education of parents and patients must
      be a priority of asthma programs.

PMID- 16798533
TI  - Developing world: asthma in a rural setting.

PMID- 16798534
TI  - Asthma: what we learn from each other's problems? The present state of asthma in
      Japan and Japanese Pediatric Guidelines for the Treatment and Management of
      Asthma (JPGTMA).

PMID- 16798535
TI  - Severe chronic asthma.
AB  - Persistent childhood asthma is more common in females with atopy with an early
      onset and may result in significant impairment of lung function. Pathological
      changes in severe chronic asthma in childhood are only partially defined and
      correlation between pathology, response to treatment and persistence is
      imprecise. Failure to respond to usual therapies requires careful consideration
      of differential diagnosis, type of inflammation present, compliance with therapy,
      and continuing monitoring and re-assessment.

PMID- 16798536
TI  - Immune responses to viral infections: relevance for asthma.
AB  - Severe respiratory viral infections in childhood are associated with the
      development of asthma later in life. Rhinovirus, respiratory syncytial virus and
      metapneumovirus are of particular importance as triggers of asthma. Effects of
      virus infection on dendritic cell function in the airways may predispose children
      to allergic sensitization. Asthmatic subjects may have impaired interferon
      responses to viral infection that also predispose to allergic sensitization.
      Difference in Toll-like receptor expression on airway epithelial cells is a
      potential mechanism for the altered immune responses of asthmatic children.

PMID- 16798537
TI  - Antimicrobial resistance: mechanisms and strategies.
AB  - Antimicrobial resistance is a growing threat worldwide. S. aureus strains that
      combine resistance and virulence genes have become a major treatment problem in
      Europe and the U.S. Extended-spectrum beta-lactamases are an emerging problem in
      many settings. Resistance mechanisms have been found for every class of
      antibiotic agent. Development of new classes of antibiotics or more robust
      versions of old classes will be essential in the years to come. Judicious use of
      antimicrobial agents and improved infection control methods must become health
      care priorities.

PMID- 16798538
TI  - Advances in diagnosis and therapy of childhood tuberculosis.
AB  - Tuberculosis remains a major health problem worldwide. Recently developed
      diagnostic blood tests may supplant or supplement TB skin test in some settings.
      Emergence of drug-resistant strains remains a global concern. New anti
      tuberculous agents are being developed and are greatly needed. There is mounting
      evidence that BCG has significant effectiveness in prevention, but development of
      improved vaccines for tuberculosis should remain a priority.

PMID- 16798539
TI  - TB in developing countries: diagnosis and treatment.
AB  - Childhood tuberculosis poses great challenges to the public health manager as
      well as the pediatrician. While mycobacterial detection and isolation remain the
      gold standard but has a poor sensitivity for several reasons. The diagnosis of
      the disease is often based on indirect methods like PPD positivity, radiological
      features and history of contact. Serology and PCR based diagnostic methods have
      failed to help a clinician working at the peripheral level. The review shares and
      discusses the place of the various tests in the diagnosis of tuberculosis. WHO
      has been propagating the use of intermittent supervised treatment for all cases
      including children. We discuss the concerns of the pediatricians and share our
      experience on this therapy.

PMID- 16798540
TI  - Community-acquired pneumonia.
AB  - Pneumonia is highly prevalent in both developed and developing countries. In this
      review we list the main organisms affecting children with pneumonia and we
      propose a summary of the best possible diagnostic and therapeutic measures.

PMID- 16798541
TI  - Pneumonia in the developed world.

PMID- 16798542
TI  - Multiple-breath washout in preschool children--FRC and ventilation inhomogeneity.
AB  - The open-circuit multiple-breath inert gas washout method is used to measure
      functional residual capacity and also to quantify ventilation distribution. The
      technique is readily applicable in preschool children as it requires quiet tidal
      breathing. Guidelines for data collection and interpretation in this age group
      will shortly be published by the European Respiratory Society and the American
      Thoracic Society.

PMID- 16798544
TI  - Atypical CF and CF related diseases.
AB  - The clinical characteristics of atypical CF are: symptoms that may start in
      infancy but the disease become clinically significant only after 10 years of age,
      survival into adulthood, chronic sinopulmonary disease, pancreatic sufficiency,
      and sweat chloride <60 meq/L. Other patients may present with single organ
      involvement such as CBAVD, biliary cirrhosis and portal hypertension, chronic or
      recurrent pancreatitis, giant nasal polyposis or hypochloremic alkalosis. It is
      recommended to refer such patients for CFTR genotyping, however, absence of known
      common mutation does not rule out CFTR associated disease, since mutations
      causing atypical CF are rare and whole genome scan is required for their
      identification. Nasal PD measurements may be helpful to establish the diagnosis
      of these patients; however, measurements might be also atypical. Several
      explanations have been suggested to explain the atypical CF disease.

PMID- 16798543
TI  - New tests for cystic fibrosis.
AB  - Most patients presenting with symptoms and signs of CF are still diagnosed on the
      basis of a sweat test. CFTR mutation analysis is useful in confirming the
      diagnosis, screening family members, newborn screening programmes and in those
      with borderline or normal sweat tests with a high index of suspicion. Nasal PD
      can also be helpful in the latter group, although there are a number of caveats
      to its use and interpretation.

PMID- 16798546
TI  - Diagnosing and managing infection in CF.
AB  - Acute and chronic bacterial infections of the lower respiratory tract remain one
      of the hallmarks of cystic fibrosis lung disease. We here review some of the
      controversial areas of diagnosing airway infection in CF patients including the
      use of techniques such as induced sputum and bronchoalveolar lavage. Treatment
      strategies have evolved over the years and there is ongoing discussion as to
      whether to treat on the basis of symptoms, positive cultures alone or
      continuously regardless of clinical and laboratory findings. Prophylactic
      antibiotic therapy with anti-staphylococcal antibiotics has been linked to a
      higher incidence of P. aeruginosa infection, but it is still unclear whether this
      side effect is limited to broader spectrum antibiotics such as cephalosporins.
      Early antibiotic therapy against P. aeruginosa has become an accepted treatment
      strategy as it not only delays the onset of chronic infection, but also leads to
      eradication of the organism in the majority of patients. So far no evidence
      exists that combination therapy is superior to inhaled therapy alone. In
      addition, the optimal duration of therapy type of inhaled antibiotic as well as
      the optimal dose has not been clarified. Studies are currently ongoing to resolve
      these issues.

PMID- 16798545
TI  - Diagnosing and managing cystic fibrosis in the developing world.
AB  - Cystic fibrosis (CF), earlier believed to be non existent in non Caucasians, is
      now a pan ethnic disease, having being reported from various regions of the world
      over last one decade. Apart from limited resources, the major problems in
      diagnosis and management of CF in developing countries include: lack of awareness
      among pediatricians, absence of facilities for diagnosis (sweat chloride
      estimation and genetic studies), lack of trained manpower for care of specific
      problems, and non availability of appropriate drugs. Care of children with CF may
      not be a priority for governments in countries where childhood mortality rates
      are high, predominantly due to acute infections. An indigenously developed and
      relatively inexpensive method of sweat collection and chloride estimation using
      pilocarpine iontophoresis and titration, respectively, may be an alternative to
      the commercially available costly equipment. Having a team of trained nurse,
      physiotherapist, and dietician for optimal care of CF patients may not be
      feasible due to inadequate resources. Training a single person (e.g. nurse) to
      deliver comprehensive CF care may be a feasible alternative. To overcome problems
      of non availability of appropriate drugs (enzymes, inhaled antibiotics, DNAse,
      etc), locally available drugs may be used. Examples include use of hypertonic
      saline in place of DNAse, enteric coated enzyme tablets in place of enteric
      coated spherules, etc. Factors that are associated with decreased survival in CF
      patients from developing countries are age of onset of symptoms <2 months, severe
      malnutrition at the time of diagnosis, colonization with Pseudomonas at the time
      of diagnosis and frequency of pneumonia >4 episodes/year. All these factors can
      be modified except onset of symptoms before 2 months of age, by early diagnosis
      and appropriate treatment. Many of the above mentioned hurdles have been
      successfully overcome by us to establish CF services in a resource-limited
      setting. We conclude that education of pediatricians about the disease, early
      diagnosis using indigenous technology and aggressive physiotherapy with
      nutritional management and judicious use of antibiotics can improve the quality
      of life and survival in CF patients in resource-limited settings.

PMID- 16798548
TI  - Insulin deficiency.

PMID- 16798547
TI  - Infection and inflammation CF: management of the basics upper airway diseases.

PMID- 16798549
TI  - Sex, drugs, and rock n' roll: the problems of adolescent cf and asthma.
AB  - This article reviews recent literature on risky behaviors in adolescents,
      suggests ways to assess the extent of the problem and proposes intervention for
      health care providers.

PMID- 16798550
TI  - Gene and cell therapy for cystic fibrosis.
AB  - Since the discovery of the CF gene over a decade ago, several groups worldwide
      have explored the potential of gene therapy, the insertion of a normal copy of
      the gene into the respiratory epithelium. Both viral and synthetic gene transfer
      agents have been designed to this end, although problems with repeat application
      have occurred with the former have occurred. Here, we will briefly review success
      in clinical trials to date. Cell therapy, replacement of the CF cell with a
      healthy, normal cell, is at a much earlier stage of development, studies mainly
      being preclinical or observational. Some evidence of plasticity of, for example,
      bone marrow cells, has been demonstrated, although for the airway, levels of
      correction appear to be extremely low and a degree of damage seems to be a
      prerequisite. Whether this approach will be able to achieve clinical success
      remains to be seen.

PMID- 16798551
TI  - Mutation specific therapy in CF.
AB  - CFTR mutations cause defects of CFTR protein production and function by different
      molecular mechanisms. The mutations can be classified according to the mechanisms
      by which mutations disrupt CFTR function. This understanding of the different
      molecular mechanism of CFTR dysfunction provides the scientific basis for
      development of targeted drugs for mutation specific therapy of CF. Class I
      mutations are nonsense mutations that result in the presence of premature stop
      codon that leads to the production of unstable mRNA or the release from the
      ribosome of a short truncated protein that is not functional. The aminoglycoside
      antibiotics can suppress premature termination codons by disrupting translational
      fidelity and allowing the incorporation of an amino acid, thus permitting
      translation to continue to the normal termination of the transcript. Class II
      mutations cause impairment of CFTR processing and folding in the Golgi. As a
      result the mutant CFTR is retained in the ER and eventually targeted for
      degradation by the quality control mechanisms. Chemical and molecular chaperons
      such as Sodium-4-phenylbutyrate can stabilize protein structure, and allow it to
      escape from degradation in the ER and be transported to the cell membrane. Class
      III mutations disrupt the function of the regulatory domain. CFTR is resistant to
      phosphorylation or ATP binding. CFTR activators such as alkylxanthines (CPX) and
      the flavonoid genistein can overcome the affected ATP binding through direct
      binding to a nucleotide binding fold. In patients carrying class IV mutations,
      phosphorylation of CFTR results in reduced chloride transport. Increases in the
      overall cell surface content of these mutants might overcome the relative
      reduction in conductance. Alternatively restoring native chloride pore
      characteristics pharmacologically might be effective. Activators of CFTR at the
      plasma membrane may function by promoting CFTR phosphorylation, by blocking CFTR
      dephosphorylation, by interacting directly with CFTR, and/or by modulation of
      CFTR protein-protein interactions. Class V mutations affect the spicing machinery
      and generate both aberrantly and correctly spliced transcripts, the level of
      which vary among different patients and among different organs of the same
      patient. Splicing factors that promote exon inclusion or factors that promote
      exon skipping can promote increase of correctly spliced transcripts, depending on
      the molecular defect. Inconsistent results were reported regarding the required
      level of corrected or mutated CFTR that has to be reached in order to achieve
      normal function.

PMID- 16798552
TI  - Plethysmographic specific airway resistance.
AB  - sRaw measurements are feasible in children from 2 years of age. sRaw allows
      clinical monitoring and research during this critical period of growth and
      development in early life. sRaw measurements promise to bridge the gap of lung
      function measurements between infancy and school age.

PMID- 16798553
TI  - CF-Emerging therapies: Modulation inflammation.
AB  - Persistent and dysregulated inflammation, combined with an exaggerated host
      response is a major contributor to CF lung disease. As lung disease progresses,
      neutrophil accumulation in the airways ensues. Modulation of CF airway
      inflammation may result in either beneficial or deleterious side effects,
      resulting in more harm than good. Antibiotics, in particular, macrolides which
      act as a long-term anti-inflammatory agent with an excellent safety profile, and
      dornase alpha, are very interesting agents; steroids are not indicated in CF
      except in very special situations, and other promising agents such as leukotriene
      modifiers, high-dose N-acetylcysteine, anti-elastase and anti-cytokines require
      further research. Research should focus on early treatment, before lung damage
      has occurred.

PMID- 16798554
TI  - Persistent pulmonary hypertension of the newborn.
AB  - In utero, fetal pulmonary vascular resistance (PVR) is high, but rapidly falls
      after birth. Expansion of the lungs, increase in oxygenation, release of
      vasoactive mediators, growth factors and remodeling of the vascular wall, all
      contribute to the reduction in PVR. Persistent pulmonary hypertension of the
      newborn (PPHN) is defined as a failure of the pulmonary vasculature to relax at
      birth, resulting in hypoxemia. PPHN is in fact a variety of disorders that have a
      common presentation. Some of the pathophysiological mechanisms and the
      therapeutic approaches are discussed below.

PMID- 16798555
TI  - Pulmonary hypertension in older children: new approaches and therapies.

PMID- 16798556
TI  - Laryngeal function and nasal ventilatory support in the neonatal period.
AB  - Nasal application of positive airway pressure, either intermittently or
      continuously, is increasingly used in the neonatal period. An important
      difference however when using a nasal interface as opposed to an endotracheal
      tube for ventilatory support is the interposition of the larynx. Recent animal
      studies from our laboratory showed that nasal ventilatory support in the neonatal
      period can significantly impact laryngeal function. This includes active
      laryngeal closure against intermittent positive pressure ventilation, which can
      limit lung ventilation, and inhibition of non-nutritive swallowing, which may
      delay swallowing maturation. Those novel findings are highly relevant to neonatal
      respiratory care. Additional studies are underway to uncover both the mechanisms
      involved and consequences on lung ventilation and swallowing function.

PMID- 16798557
TI  - Ventilator strategies--what monitoring is helpful?

PMID- 16798558
TI  - High frequency oscillation and liquid ventilation.
AB  - During high frequency oscillation ventilation (HFOV) small tidal volumes are
      delivered at fast frequencies, usually between 10 and 15 Hz. Meta-analysis of
      randomised trials of prophylactic HFOV versus conventional ventilation have
      demonstrated only a modest reduction in BPD amongst survivors in the HFOV groups.
      Similarly, no long term advantages of HFOV have been highlighted when it is used
      as rescue mode, but there have been few randomised studies. During liquid
      ventilation, the lungs are filled with perfluorocarbon, which, compared to water,
      has low surface tension and a high solubility for respiratory gases. Clinical
      experience of liquid ventilation is limited, but improvements in oxygenation and
      lung function have been shown in short term studies.

PMID- 16798559
TI  - Bronchopulmonary dysplasia--long term follow up.
AB  - Fifty percent of BPD infants require readmission to hospital during infancy,
      particularly if they suffer an RSV infection. Many BPD infants require
      supplementary oxygen at home, early discharge can be achieved if those still
      requiring nasogastric feeding are given appropriate community support.
      Troublesome respiratory symptoms are common in children who had BPD, as are lung
      function abnormalities even in adolescents and young adults.

PMID- 16798560
TI  - ARDS--long term follow up.

PMID- 16798561
TI  - ECMO--long term follow-up.

PMID- 16798562
TI  - Exercise testing and chronic lung diseases in children.
AB  - Exercise activity is an important part of daily life for both healthy children
      and children with respiratory diseases. Overall fitness level and responses to
      exercise can be assessed through cardiopulmonary exercise tests (using a
      treadmill or a cycloergometer). In asthmatic children exercise tests are useful
      to diagnose exercise-induced bronchoconstriction, which may affect up to 80% of
      asthmatic subjects. In cystic fibrosis patient, as the disease progresses, lung
      function deteriorates and exercise tolerance likewise diminishes. This reduced
      tolerance may not be predicted on the base of a standard spirometry while an
      exercise test can offer useful information. Eventually, exercise testing is
      useful in children with bronchopulmonary dysplasia to determine any presence and
      extent of gas exchange and ventilation dysfunction during exercise. Exercise
      challenges are a valuable tool to assess exercise tolerance that may be not
      adequately reflected by resting lung function tests.

PMID- 16798564
TI  - Introduction and overview of preschool lung function testing.

PMID- 16798563
TI  - Home and hospital monitoring for ALTE.
AB  - Apparent life-threatening events (ALTE) results from various causes. Documented
      monitoring of cardiorespiratory parameters and Hb-O(2) saturation by pulse
      oximetry (SpO(2)) has proven useful in the identification of significant events
      both in hospital and at home. Home monitoring might be especially helpful for
      infants with recurrent but infrequent clinical events not captured during a
      hospital admission.

PMID- 16798565
TI  - Exhaled NO and breath condensate.
AB  - A growing interest has recently directed toward non invasive methods, such as
      exhaled nitric oxide (FE(NO)) measurement and exhaled breath condensate (EBC)
      collection, for the assessment of asthmatic inflammation. FE(NO) is a reliable
      marker of eosinophilic airway inflammation and it can be measured by means of a
      standardized technique in children starting from the age of 4. FE(NO) may have
      useful applications both in asthma diagnosis and monitoring. EBC is obtained
      cooling exhaled air and its composition is believed to mirror the characteristics
      of airway lining fluid. The compounds detected in EBC are markers of inflammation
      and oxidative stress occurring in asthmatic lung. While EBC is still only a
      research tool, FENO measurement is closer to clinical practice and lately it has
      been included in some treatment algorithms for asthma.

PMID- 16798567
TI  - Tracheostomy in children.
AB  - Indications, timing, and interventions to the airway resulting in tracheostomy
      are poorly characterised. There are no promulgated standards of care for
      tracheostomy in children. This paper addresses the issues associated with
      decision for tracheostomy, the timing of the intervention, the care for the
      tracheostomy in both the acute and chronic phase and the necessities for care at
      home. The paper attempts to describe some of the apparent problems associated
      with tracheostomy and practical techniques for treatment of the inadvertent
      complications.

PMID- 16798566
TI  - Sleep studies: which technologies?
AB  - The demand for sleep services for young patients has escalated due to the
      increased recognition of pediatric sleep disorders over the past two decades. In
      this overview, we will highlight the essentials of pediatric sleep monitoring and
      stress particular issues that require the awareness of clinicians evaluating
      children for sleep disorders. While many techniques used in the "adult" sleep
      centers may suffice for the older adolescent patient, specific tailoring of the
      design of the sleep center to younger children and their families, and attention
      to the age-sensitive components of sleep data acquisition and interpretation are
      increasingly important in younger children. Several promising newer technologies
      and their potential for future clinical utility will be also reviewed.

PMID- 16798568
TI  - Spinal muscular atrophy type 1: what are the ethics and practicality of
      respiratory support?
AB  - Spinal Muscular Atrophy Type I (SMA I) is the most severe form of SMA. It
      presents in infancy and without treatment death occurs by 2 years. Treatments in
      use address respiratory and nutritional issues but even with aggressive treatment
      death is still likely in childhood. Thus their use is not obligatory. However,
      pediatric respirologists must be willing and comfortable at presenting all
      treatment options, including the option of palliative care, to families and then
      supporting the family's choice. Whatever the chosen treatment regimen, decision
      making is difficult for families. Support and help must be provided from the time
      of presentation till death by a knowledgeable and compassionate team.

PMID- 16798569
TI  - Physiology of mucus clearance.

PMID- 16798570
TI  - The pharmacologic approach to airway clearance: mucoactive agents.
AB  - The term "mucoactive agent" refers to any medication used to improve the
      clearance of airway secretions. It is not synonymous with the word "mucolytic" as
      this strictly means a drug that decreases the viscosity of secretions. In many
      cases, decreased viscosity will adversely affect cough transport. For this reason
      many of the older mucolytic agents such as acetylcysteine are not effective for
      the therapy of lung disease and their use is not recommended. I review here the
      many classes of mucoactive agents and identify a number of medications with great
      promise for the treatment of chronic airway disease.

PMID- 16798571
TI  - Physiotherapy and airway clearance techniques and devices.

PMID- 16798572
TI  - Global pediatric pulmonology: what is coming to the West--out of India?
AB  - With the increasing globalisation, immigration and travel there are increasing
      opportunities for the exotic diseases to be seen in different settings. This
      paper highlights pulmonary diseases seen in the Indian subcontinent. It discusses
      briefly the clinical features and management of Tropical Pulmonary Eosinophilia,
      Hydatid disease of the lungs, Malarial lung pathology. In addition, the low cost
      medical innovations evolved to use the newer medical technologies, in an
      affordable fashion, in a developing countries context have been detailed.

PMID- 16798573
TI  - Global paediatric pulmonology: out of Africa.
AB  - Respiratory illness is the major cause of mortality and morbidity in African
      children. The spectrum of disease includes acute and chronic respiratory illness.
      As a result of the HIV epidemic currently occurring in sub-Saharan Africa, HIV
      associated acute and chronic respiratory disease has emerged as a major factor in
      the epidemiology of childhood respiratory illness. Pneumonia is the leading
      causes of childhood mortality responsible for approximately 21% of deaths in
      African children under five years of age each year. The HIV pandemic has
      increased the incidence, severity and pneumonia mortality in African children.
      Pulmonary tuberculosis (TB) is an important cause of morbidity and death.
      Globally, the highest TB incidence rates occur in sub-Saharan African countries;
      many of these countries are also experiencing a dual HIV epidemic, resulting in
      an exponential increase in TB cases. The burden of childhood respiratory illness
      has necessitated novel and improved ways of diagnosis, treatment and prevention,
      particularly in the context of limited resources. Improved diagnosis, treatment
      and prevention of pneumonia have been a research focus, particularly in HIV
      infected children. African studies have provided information on the epidemiology,
      aetiology and outcome from pneumonia in HIV-infected and uninfected children. The
      efficacy of trimethoprim-sulphamethoxazole prophylaxis in reducing mortality and
      morbidity in HIV-infected African children was shown in the only randomized
      controlled trial. Two large studies have shown the efficacy of the pneumococcal
      conjugate vaccine in an African context. Regarding TB, areas of research include
      diagnostic studies and improved preventative strategies. Promising diagnostic
      studies for childhood TB include the use of sputum induction, PCR techniques and
      blood interferon assays. The immune reconstitution inflammatory syndrome (IRIS)
      has emerged as a new clinical entity in HIV-infected children with TB associated
      with use of antiretroviral therapy. New preventative strategies for TB include
      novel vaccines and primary prophylaxis. Available, effective interventions for
      prevention and treatment of childhood respiratory disease exist; the challenge is
      to achieve widespread implementation and high coverage rates in African
      countries. Greater access to newer vaccines and, in HIV-infected children, to
      anti-retroviral therapy and prophylaxis is necessary to further reduce the burden
      of childhood respiratory illness in Africa.

PMID- 16798574
TI  - Out of the East--emerging infections.

PMID- 16798575
TI  - Assessment of bronchial responsiveness in preschool children.
AB  - Preschool children have a short concentration span and relatively poor
      cooperation with pulmonary function tests (PFTs). This combination complicates
      the inhalation protocol and the assessment of bronchodilation/bronchoconstriction
      in this age group. Bronchial responsiveness can be studied after bronchodilator
      administration or during bronchial challenge using miscellaneous PFTs. This
      article enclosed information on when to consider significant a PFT change, and
      published proposed cutoffs for bronchodilation/bronchoconstriction test. Issues
      on interpretation of bronchial test are also discussed. Recommendations are
      provided on behalf of the Interrupter Technique Subcommittee of the ATS/ERS
      Working Group on Infant and Young Children Pulmonary Function Testing.

PMID- 16798576
TI  - Pulmonary complications of neuromuscular disease.

PMID- 16798577
TI  - The lung and the gut: common origins, close links.
AB  - Because of the common embryologic origin, alteration of the many factors
      modulating the development of the alimentary and the respiratory tract often
      results in structural abnormalities involving the two systems. Indeed, some of
      the most common embryologic disorders of the airways are frequently associated
      with anomalies of the gastrointestinal tract. Lung growth occurs as a series of
      tightly regulated events, depending on a number of factors, including
      developmental, genetic and environment ones. Abnormalities of any of these
      factors may causes developmental alterations of the lung leading to a group of
      disorders termed "bronchopulmonary-foregut malformations". These are usually
      sporadic, solitary cystic hamartomas, involving conducting airways, arteries,
      venous drainage, and lung parenchyma, which are now often discovered on routine
      prenatal sonography. While some lesions may be large and cause serious
      complications in the foetus or newborn, many will be asymptomatic at birth,
      raising controversy about management: simple observation or surgery and, if so,
      at what age? Over the past two decades molecular studies have started to shed
      light on the complex series of events that control proper formation of the lung,
      with the hope that a better understanding of the molecular basis of pulmonary
      maturation will allow the design of new therapeutic strategies.

PMID- 16798578
TI  - Genetic disorders of surfactant homeostasis.
AB  - Pulmonary surfactant reduces surface tension at the air-liquid interface in the
      alveolus, thereby maintaining lung volumes during the respiratory cycle. In
      premature newborn infants, the lack of surfactant causes atelectasis and
      respiratory failure, characteristic of respiratory of distress syndrome.
      Surfactant is comprised of lipids and associated proteins that are required for
      surfactant function. Surfactant proteins B and C and a lamellar body associated
      transport protein, ABCA3 play critical roles in surfactant synthesis and
      function. Mutations in the genes encoding these proteins cause lethal respiratory
      distress in newborn infants. This review discusses the clinical and pathological
      findings associated with these inherited disorders of alveolar homeostasis.

PMID- 16798579
TI  - Pulmonary vasculitides in children.

PMID- 16798580
TI  - How to evaluate and treat children's interstitial lung disease.

PMID- 16798581
TI  - Disorders of lung morphogenesis.
AB  - Perinatal lung function depends upon formation of the conducting and gas exchange
      regions of the lung. The precise expression of transcription factors and
      signaling molecules is required for normal lung morphogenesis.

PMID- 16798582
TI  - Diaphragmatic hernia--pre and postnatal.

PMID- 16798583
TI  - Paediatric basis of adult lung disease.
AB  - Most lung disease throughout life is programmed in utero or early post-natal
      life. Factors in the fetal environment such as maternal smoking and diet can lead
      to reduced lung function, immunological modification or symptoms from birth.
      There are clear genetic components documented for cystic fibrosis, alpha1 anti
      trypsin deficiency and asthma. In early life, the outcomes for those predisposed
      to asthma or allergy appear to be dependent on the relative timing of exposure to
      infective agents, allergens or helminths. Abnormal airway structure is present in
      both transient and persistent wheezers. New drugs and environmental manipulations
      will need to be developed with an understanding of the mechanisms associated with
      this early programming.

PMID- 16798584
TI  - Non cystic fibrosis bronchiectasis.

PMID- 16798585
TI  - Respiratory aspects of Riley-Day Syndrome: familial dysautonomia.

PMID- 16798586
TI  - Clinical implications of pulmonary function testing in preschool children.
AB  - There is increasing recognition of the need for objective physiological
      measurements of lung function during the preschool years in order to identify and
      treat early lung disease before irreversible structural changes occur; monitor
      disease progression and efficacy of therapeutic interventions and distinguish the
      various wheezing phenotypes that occur in this age group, all of which require
      different management strategies. While preschool pulmonary function tests are
      undoubtedly excellent research tools , their role in the clinical management of
      the individual young child remains more controversial. In particular, further
      work is required to establish information on the within-subject, between occasion
      variability and the relative sensitivity and specificity of each technique, as
      well as developing more appropriate prediction equations for this age group,
      before they can be used confidently in the clinical management of individual
      child. This review examines the various challenges facing paediatricians who are
      responsible for children with respiratory diseases such as asthma, wheezing,
      cystic fibrosis and chronic lung disease following preterm delivery and
      summarises recent recommendations from an ATS/ERS Task Force.

PMID- 16798587
TI  - The upper airway: congenital malformations.
AB  - The upper airway extends from the nasal aperture to the subglottis and can be the
      site of multiple types of congenital malformations leading to anatomical or
      functional obstruction. This can cause severe respiratory distress. Newborns are
      obligate nasal breathers; therefore nasal obstruction can lead to airway
      compromise and respiratory distress. The etiologies are varied and include,
      choanal atresia, pyriform aperture stenosis, and rarely tumors such as glioma,
      encephalocele, teratoma, or dermoid. More common upper airway congenital
      anomalies include laryngomalacia, vocal cord paralysis, and subglottic stenosis.
      Laryngolmalacia is the most common congenital laryngeal anomaly. Inspiratory
      stridor often does not present until two weeks after birth and resolves by 18
      months of age. Most cases are managed with watchful waiting. Severe cases require
      a surgical intervention. Bilateral vocal cord paralysis is usually idiopathic. In
      certain cases, paralysis may occur secondary to central nervous system
      abnormality including Arnold-Chiari malformation, cerebral palsy, hydrocephalus,
      myelomeningocele, spina bifida, or hypoxia. Severe cases may necessitate
      endotracheal intubation and tracheostomy. Congenital subglottic stenosis is the
      third most common laryngeal anomaly. It is defined as a diameter of less than 4mm
      of the cricoid region in a full-term infant, and less than 3mm in a premature
      infant. This condition is the most common laryngeal anomaly that requires
      tracheotomy in newborns. Laryngotracheoplasty may be required to achieve
      decanulation. Knowledge of the upper airway embryological development and
      congenital anomalies is off prime importance in assessing the newborn with
      respiratory distress. In most cases flexible endoscopy establishes the diagnosis.
      Management is tailored to each condition and its degree of severity.

PMID- 16798589
TI  - Applying physiology to conventional mechanical ventilation.
AB  - It is important to understand the physiology that underlies how patients get into
      respiratory difficulty and how they can be supported to overcome these
      difficulties. This article reviews the physiological principles that underpin
      decision making about support for patients with respiratory difficulties, whether
      they are related to inadequate oxygenation or ventilation.

PMID- 16798588
TI  - Lung function in preschool children: applications in clinical and epidemiological
      research.
AB  - During recent years there has been significant development of pulmonary function
      tests for use in preschool children. A range of tests including multiple inert
      gas washout, plethysmography, spirometry, interrupter resistance and impulse
      oscillometry have been shown to be feasible and to be able to identify diminished
      lung function in children with lung disease such as asthma or cystic fibrosis. An
      overview of these applications in clinical and epidemiological research is given.
      Future applications to investigate the longer term effect of preterm delivery,
      intra-uterine growth retardation, smoking and assessing the response to
      therapeutic intervention would strengthen the scientific basis for the prevention
      and treatment of respiratory disease in early life.

PMID- 16798590
TI  - Monitoring during mechanical ventilation.

PMID- 16798591
TI  - Imaging of pediatric chest masses.

PMID- 16798592
TI  - Application of PET/CT in children.

PMID- 16798593
TI  - Pearls and pitfalls in HRCT in children.
AB  - The aim of this talk is to discuss the role of thin slice high resolution CT in
      paediatric practice and to describe the various means by which these images can
      be acquired to a satisfactory [diagnostic] level in routine paediatric practice.
      It is also to highlight the utility of HRCT in paediatric practice to enable the
      various patterns of disease processes to be understood. The main role for HRCT is
      in the diagnosis and follow up of diffuse airways and interstitial lung diseases
      in children. We will focus on the utility of HRCT in diagnosis of paediatric
      diffuse interstitial lung disease [DILD] and the inherent strengths and weakness
      within the ultimate choices made to acquire images. We will emphasise and
      illustrate the specific conditions for which HRCT provides a powerful diagnostic
      tool.

PMID- 16798594
TI  - Interrupter resistance: what's feasible?
AB  - Interrupter resistance (Rint) is one of the easiest ways to assess respiratory
      resistance during tidal breathing with minimal subject cooperation. This article
      enclosed current knowledge on technical and practical aspects such as how to
      measure Rint, and how to calculate Rint. Issues on repeatability of the technique
      and bronchial responsiveness are discussed. Recommendations on Rint technique are
      provided on behalf of the Interrupter Technique Subcommittee of the ATS/ERS
      Working Group on Infant and Young Children Pulmonary Function Testing.

PMID- 16798595
TI  - Practical aspects of scoring sleep in children.
AB  - As the indications for pediatric polysomnography expand, and the high prevalence
      of sleep disorders in childhood becomes increasingly recognized, there is a need
      for enabling practicing physicians to identify correctly events occurring in
      polysomnographic tracings. A summary description of the most salient features of
      the various sleep states and of the characteristics and visual patterns
      corresponding to frequent events among several recognized diseases is provided.

PMID- 16798596
TI  - Periodic limb movement disorder in children.
AB  - Periodic limb movement disorder (PLMD) has been reported in children and is more
      prevalent in certain conditions such as attention deficit hyperactivity disorder.
      The International Restless Legs Syndrome Group has recently developed the
      criteria for diagnosis of PLMD in children. These criteria include both specific
      clinical features and polysomnographic findings. Exclusion of other causes
      especially sleep-disordered breathing is essential. Several medications including
      benzodiazepine and dopaminergic medication have been used in children, although
      these medications have not been adequately studied in this age group. Some PLMD
      children have evidence of low iron storage and response favorably to iron
      therapy.

PMID- 16798597
TI  - Sleep apnea in children--treatment considerations.
AB  - The prevalence of obstructive sleep apnea (OSA) is clearly increasing in the
      pediatric population. However, the polysomnographic criteria for treatment still
      remain to be defined by appropriate scientific methodology. Furthermore, the
      overall efficacy of currently available interventions such as surgical removal of
      enlarged tonsils and adenoids (T&A) is unknown, such that we are currently unable
      to precisely define who the high risk patients are, and the cost and benefits
      associated with any given treatment. Here, we review the available approaches to
      the management of OSA in the pediatric population, and examine the potential
      complementary role of anti-inflammatory therapy, mask ventilation, and intra-oral
      appliances in the context of mild OSA or residual OSA following T&A.

PMID- 16798598
TI  - Fluid clearance from the lungs of newborns, infants and children.

PMID- 16798599
TI  - Acute and chronic cough.
AB  - Cough is a normal protective mechanism which occurs many times every day. Cough
      with a viral infection lasts up to 2 weeks in 70-80% of children. Cough present
      for more than 4 weeks may be due to a recognized specific cause or non specific
      and considered protracted bronchitis. Chronic cough in children is different to
      that in adults and rarely due to GE reflux, postnasal drip or asthma. Treatment
      addresses the specific cause and symptomatic treatment is rarely needed or
      effective.

PMID- 16798600
TI  - Pediatric asthma: how significant it is for the whole life?
AB  - Asthma is most frequent chronic disease in childhood. Childhood asthma frequently
      persists to adulthood and the available evidence suggests that the severity of
      childhood asthma predicts the severity of asthma in the adulthood. To prevent
      long term remodeling of the airways and improve prognosis, early diagnosis and
      treatment are necessary. More precise markers that would help to detect asthma
      and predict its prognosis are urgently needed.

PMID- 16798601
TI  - What's new in CF airway inflammation: an update.
AB  - Neutrophilic airway inflammation is a characteristic feature of cystic fibrosis
      (CF) lung disease and present in most patients with pulmonary manifestations of
      the disease. Here we discuss the ongoing controversy whether the CFTR mutation
      itself causes a pro-inflammatory milieu in the airways or whether inflammation is
      always secondary to infection. Since the presence of inflammation has been shown
      to be a risk factor for subsequent lung function decline, noninvasive tests to
      monitor airway inflammation are urgently needed. Induced sputum is currently
      being assessed as a clinical and research tool, but unfortunately is only
      feasible in cooperative children. While nonspecific treatment approaches that
      decrease infection or improve clearance of airway secretions were found to
      positively affect airway inflammation, specific anti-inflammatory treatment
      strategies have been less successful. Since any intervention that decreases
      inflammation may potentially have a detrimental effect by promoting airway
      infection, a better understanding of the factors regulating inflammation in the
      CF lung will form the basis for more targeted treatment strategies in the future.

PMID- 16798602
TI  - Fate of inhaled particles after interaction with the lung surface.
AB  - Inhaled particles may cause increased pulmonary and cardiovascular morbidity and
      mortality. The wall structures of airways and alveoli act as a series of
      structural and functional barriers against inhaled particles. Deposited particles
      are displaced and come into close association with epithelial cells, macrophages
      and dendritic cells. The cellular interplay after particle deposition in a triple
      cell co-culture model of the human airway wall was investigated by laser scanning
      microscopy. Furthermore, the cellular response was determined by measurement of
      TNF-alpha. Dendritic cells gained access to the apical side of the epithelium
      where they sampled particles and interacted with macrophages.

PMID- 16798603
TI  - Other medications for aerosol delivery.
AB  - Although aerosol therapy is most commonly used to treat asthma and COPD, there
      are a large number of aerosol medications now used or in development for other
      diseases. Mucoactive agents have long been available by aerosol, but now we have
      truly effective drugs to improve effective airway clearance including dornase
      alfa, hyperosmolar saline, and aerosol surfactant. Inhaled antibiotics are
      available for the treatment of cystic fibrosis, bronchiectasis and other chronic
      airway infections. With the development of devices that can target aerosol to the
      deep lung, the opportunity to deliver medications systemically by the aerosol
      route has become a reality. Insulin, recently approved in the US as aerosol
      therapy, and other peptides are systemically absorbed from the distal airway and
      alveolus. Aerosol gene transfer therapy to correct abnormalities associated with
      cystic fibrosis, primary ciliary dyskinesia and other airway diseases also holds
      great potential.

PMID- 16798604
TI  - Forced oscillation technique.
AB  - FOT may hold the promise of improving the diagnosis of airway obstruction, but
      may be even better in quantifying the magnitude of airway reversibility and hyper
      reactivity, helping in the adjustment of therapy, and monitoring disease
      progression in young children.

PMID- 16798605
TI  - Aerosol therapy: regimen and device compliance in daily practice.

PMID- 16798606
TI  - Aerosol therapy: the special needs of young children.
AB  - Efficient aerosol therapy in young children is a challenge. The aerosol
      administration method requires special features, because young children can not
      perform an inhalation manoeuvre, breath usually through the nose and may be
      distressed during the administration. The prescribing clinician should be aware
      of the advantages and disadvantages of the different inhalation devices
      available, in order to select the proper device for each individual patient. For
      maintenance asthma therapy in young children the pressurized metered dose inhaler
      (pMDI) combined with spacer is the first choice for delivering aerosols. A
      facemask can be attached if a child is unable to breath through the mouth. A
      small leak of the facemask can reduce the dose delivered dramatically, therefore
      a good seal is crucial. Lung deposition can be improved by using a pMDI with
      extra-fine particles. However, even if the most optimal device is chosen,
      cooperation during administration remains the most important determinant for
      efficient drug delivery. During crying the dose to the lungs is minimal. Optimal
      aerosol delivery to the lungs of young children can be achieved with a good
      facemask seal, good cooperation of the child, with quiet breathing and an aerosol
      with small particles.

PMID- 16798607
TI  - Aerosols: the environmental harmful effect.
AB  - Aerosols as end products of ambient indoor and outdoor pollution have some
      potential harmful effect. Children are especially at risk due to their developing
      organ systems. This is mainly true for the lungs, but may also be true for other
      organ systems, such as the immune system.

PMID- 16798608
TI  - Gene by environment interactions in respiratory tract diseases.

PMID- 16798609
TI  - What are we learning from genetic cohort studies?
AB  - Although genetic component of asthma has been well recognised, genetics alone
      cannot explain the rise in asthma prevalence. This increase is likely a
      consequence of environmental factors increasing the risk in genetically
      susceptible individuals. As wheezing illness usually begins within months of
      birth, prospective birth cohorts with detailed measures of environmental
      exposures and objective measures of disease are essential to study gene
      environment interactions in the development of different wheeze phenotypes. Such
      studies will enable identification of children at increased risk of disease
      because of a genetic predisposition when exposed to a particular environmental
      factor. Tailor-made evidence-based strategies for prevention of asthma and atopic
      sensitization applicable to individuals at risk (rather than the whole
      population) will then be developed to reduce the risk of asthma and allergy
      development.

PMID- 16798610
TI  - Inflammatory markers should be the basis of monitoring asthma. The case for the
      pro's.

PMID- 16798611
TI  - Inflammatory markers should be the basis of monitoring asthma. The case for the
      con's.

PMID- 16798612
TI  - Current pharmacological treatments for bronchiolitis are useless. The case for
      the pro's.

PMID- 16798613
TI  - Claudins--key pieces in the tight junction puzzle.
AB  - Tight junctions restrict the flow of ions and aqueous molecules between cells by
      forming a selective barrier to the paracellular pathway. Permeability of the
      tight junction barrier is determined by a class of transmembrane proteins known
      as claudins. The relationship between claudins and paracellular permeability is
      complex and determined not only by the profile of claudin expression but also by
      the arrangement of claudins and other proteins into tight junction strands. This
      review summarizes progress in understanding how claudins are assembled into tight
      junctions and how they interact with other tight junction proteins.

PMID- 16798614
TI  - Internal fluid flow increases cellular interconnects between Medial Collateral
      Ligament fibroblasts and cellular extensions within three-dimensional collagen
      matrixes.
AB  - The interconnectivity of fibroblasts within the ligamentous extracellular matrix
      has been largely overlooked. Studies on the cell-to-cell contacts with their
      neighbors via gap junctions in ligament fibroblasts, and works on the ability of
      fibroblasts to generate interconnected networks in vivo, suggest
      interfibroblastic interactions play an important role in fundamental biological
      processes, including homeostasis and wound healing. The current study examines
      how fluidic shear stresses imposed by internal flow can be used to mediate the
      formation of three-dimensional, interconnected fibroblast networks within
      collagen solutions. Several fibroblast-collagen solutions were exposed to shear
      stresses via Poiselle Flow. The consequent changes in cell networking,
      interconnections, and cell morphology within collagen matrixes exhibited by cells
      derived from Bovine Medial Collateral Ligaments were analyzed. Results illustrate
      that higher imposed stresses generate cells with more dendritic and/or branched
      morphologies, which form more visible three-dimensional networks within collagen
      matrixes than fibroblast-collagen solutions that were unexposed to shear stress.

PMID- 16798615
TI  - Direct interaction of the C-terminal domain of alpha-catenin and F-actin is
      necessary for stabilized cell-cell adhesion.
AB  - Alpha-catenin functions to anchor adherens junctions to the filamentous actin (F
      actin) cytoskeleton, through direct and indirect binding mechanisms. When
      truncated at amino acid 865, alpha-catenin exhibited a markedly reduced F-actin
      binding affinity compared to wild-type. Expression of the truncated mutant in the
      alpha-catenin deficient colon carcinoma cell line, Clone A, could not restore an
      adhesive phenotype when compared. Furthermore, the truncated alpha-catenin fusion
      protein failed to concentrate at sites of cell-cell contact, to promote
      morphological changes associated with epithelial monolayers, and to stimulate
      resistance to shearing forces in a hanging drop aggregation assay. Subsequent
      attempts to isolate single residues governing the direct F-actin interaction,
      using neutralizing charge or reverse charge mutations of basic residues within a
      homology modeled alpha-catenin C-terminal 5-helix bundle, had no effect on F
      actin cosedimentation. We conclude that direct attachment of alpha-catenin to F
      actin is required to promote cadherin-mediated contact formation and strong cell
      cell adhesive states.

PMID- 16798616
TI  - The effect of the single substitution of arginine within the RGD tripeptide motif
      of a modified neurotoxin dendroaspin on its activity of platelet aggregation and
      cell adhesion.
AB  - The Arg-Gly-Asp (RGD) tripeptide unit is a cell-cell and cell-extracellular
      matrix recognition sequence of some integrins that is found within several
      extracellular matrix glycoproteins and dendroaspin, a disintegrin-like venom
      protein isolated from the snake venom of the Dendroaspis jamsonii. In the present
      study, the RGD motif in dendroaspin was substituted by Lys-Gly-Asp (KGD), His-Gly
      Asp (HGD), Gln-Gly-Asp (QGD) and Ala-Gly-Asp (AGD) denoted as KGD-den, HGD-den,
      QGD-den and AGD-den, respectively. Each of the mutants exhibited activity as
      inhibitor of ADP-induced platelet aggregation with IC50 values of 0.26, 2.5, 6,
      and 17 microM for KGD-den, HGD-den, QGD-den, and AGD-den, respectively, as
      compared with RGD-den (IC50 = 0.18 microM). Interestingly, HGD-den was approx.
      two-fold more potent and a more selective inhibitor than either the KGD-den or
      QGD-den counterpart at blocking A375-SM human melanoma cell adhesion to
      fibrinogen (beta3-mediated). KGD-den, HGD-den, and QGD-den were preferentially
      antagonists of A375-SM human melanoma cell adhesion to fibrinogen rather than to
      fibronectin (alpha5beta1-, beta3-mediated). Both HGD-den and KGD-den were
      equipotent as inhibitors of human erythroleukaemia (HEL) cell adhesion to
      fibrinogen (IC50 = 0.15 microM) and also preferential inhibitors of HEL cell
      adhesion to fibrinogen (beta3 and beta1-mediated) rather than to fibronectin.
      These findings show that the presence of the arginine within the RGD motif of
      dendroaspin is not obligatory and substitution of this residue can modulate
      inhibitory potency and integrin binding selectivity.

PMID- 16798617
TI  - Hypoxia and ionizing radiation: changes in adhesive properties and cell adhesion
      molecule expression in MG-63 three-dimensional tumor spheroids.
AB  - The effects of chemically induced hypoxia and ionizing radiation on the adhesive
      properties of MG-63 human osteosarcoma three-dimensional spheroids were
      investigated. Hypoxia was induced by addition of CoCl2 to small, nonhypoxic
      spheroids and verified by HIF-1alpha expression. In addition, the possible role
      of important cell adhesion molecules involved in tumor dissemination in inducing
      adhesive changes were also studied. In particular, two key integrins (i.e., the
      alpha chain of the fibronectin receptor, alpha5, and the alpha chain of the
      collagen receptor, alpha2), an important member of the immunoglobulin superfamily
      (CD54 or ICAM-1) and the strategic molecule CD44 (H-CAM, the principal receptor
      for hyaluronan) were examined. Because of the important role of fibronectin in
      adhesive processes, variations in this extracellular matrix component were also
      examined. The results seem to indicate that CoCl2-induced hypoxia greatly
      increases adhesion of MG-63 spheroids to both tissue culture plates and plates
      coated with fibronectin or collagen when compared to controls, while ionizing
      radiation induces a great decrease in this attachment. Furthermore, chemically
      induced hypoxia also partially inhibits the effects of ionizing radiation. The
      data also show that these adhesive changes are accompanied by concomitant
      variations in the expression of alpha5 and alpha2 integrins, CD44, and CD54 and
      fibronectin.

PMID- 16798618
TI  - Concentration of circulating oxidized LDL in HIV-infected patients treated with
      antiretroviral agents: relation to HIV-related lipodystrophy.
AB  - BACKGROUND: Circulating oxidized LDL (ox-LDL) is associated with clinical
      manifestations of atherosclerosis. The aim of the study was to investigate the
      concentrations of ox-LDL in HIV-infected patients under antiretroviral therapy
      with (HIV-LD) or without (HIV-nLD) HIV-related lipodystrophy. METHOD: A total of
      44 HIV-infected men were enrolled in the study. Half of them had HIV-LD. The
      control group included 12 age- and body mass index (BMI)-matched HIV-uninfected
      men. Ox-LDL concentration and C-reactive protein level were determined. Insulin
      sensitivity was measured using the homeostasis model assessment (HOMA-IR). LD was
      assessed by using a validated score calculated from clinical and biological data.
      RESULTS: HIV-infected patients had significantly higher ox-LDL concentrations
      when compared to HIV-negative controls (0.8 +/- 0.3 mg/dL vs. 0.60 +/- 0.1 mg/dL;
      p = .007). HIV-LD patients had significantly higher ox-LDL concentrations than
      HIV-nLD patients (0.91 +/- 0.38 and 0.69 +/- 0.16; p = .04). In HIV-LD patients,
      current therapy with protease inhibitors (PIs); duration of PI therapy; HOMA-IR;
      and time exposure to stavudine, efavirenz, ritonavir, saquinavir, and amprenavir
      were significantly higher than in HIV-nLD patients. In multivariate analysis,
      time exposures to stavudine and ox-LDL concentration were independently related
      to lipodystrophy. CONCLUSION: The high concentration of ox-LDL was found in HIV
      infected patients under antiretroviral therapy, especially in those with
      lipodystrophy.

PMID- 16798619
TI  - Tenofovir-containing nucleoside/nucleotide-only antiretroviral maintenance
      therapy: decision making and virological outcome.
AB  - OBJECTIVE: To assess the virological outcome of patients with undetectable human
      immunodeficiency (HI) viremia switched to tenofovir (TDF)-containing
      nucleosideonly (NUKE-only) treatments and to investigate the factors influencing
      the physicians' decision for application of a nonestablished therapy. METHOD:
      Patients' characteristics and history were taken from the cohort database. To
      study the decision-making process, questionnaires were sent to all treating
      physicians. RESULTS: 49 patients were changed to TDF-containing NUKE-only
      treatment and 46 had a follow-up measurement of HI viremia. Virological failure
      occurred in 16 (35%) patients. Virological failure was associated with previous
      mono or dual therapy and with a regimen including didanosine or abacavir. No
      failure occurred in 15 patients without these predisposing factors. The main
      reasons for change to TDF-containing NUKE-only treatment were side effects and
      presumed favorable toxicity profile. The rationale behind this decision was
      mainly analogy to the zidovudine/lamivudine/abacavir maintenance therapy.
      CONCLUSION: TDF-containing NUKE-only treatment is associated with high early
      failure rates in patients with previous nucleoside reverse transcriptase
      inhibitor mono or dual therapy and in drug combinations containing didanosine or
      abacavir but not in patients without these predisposing factors. In HIV medicine,
      treatment strategies that are not evidence-based are followed by a minority of
      experienced physicians and are driven by patients' needs, mainly to minimize
      treatment side effects.

PMID- 16798620
TI  - Serious renal impairment occurs rarely with use of tenofovir DF.
AB  - PURPOSE: The purpose of this study was to evaluate the short-term effects (up to
      6 months) of tenofovir disoproxil fumarate (DF) use on renal function in patients
      being treated for HIV-1 infection. METHOD: The charts of 447 HIV-1-infected
      patients who received at least three months of tenofovir DF treatment were
      reviewed. Data collected included demographics, concurrent antiretrovirals, other
      concurrent medications, CD4 counts and HIV-1 viral loads, and serum creatinine
      values while on tenofovir DF. Data collection was truncated at 6 months. RESULTS:
      Baseline serum creatinine (SCr) was 1.0 mg/dL, with a calculated creatinine
      clearance (CLCr) of 95.2 mL/min (using the Cockroft-Gault equation). There was no
      significant change in SCr or CLCr at 12 weeks (1.1 mg/dL and 92.7 mL/min,
      respectively) or 24 weeks (1.1 mg/dL and 92.9 mL/min, respectively). All three
      patients with grade 2 increases in SCr had other medical reasons for an increased
      SCr (one patient each had indinavir-associated nephrolithiasis, lactic acidosis,
      and pancreatitis). No patients experienced any complications from these increases
      in SCr. CONCLUSION: Increases in SCr and CLCr within the first 6 months of
      tenofovir DF therapy were rare. Although no clinical nephrotoxicity was observed,
      continued observation of renal function is warranted in patients predisposed to
      renal impairment.

PMID- 16798621
TI  - Therapeutic drug monitoring in HIV treatment: a literature review.
AB  - PURPOSE: Therapeutic drug monitoring (TDM) is the practice of managing plasma
      drug concentrations. This intervention can potentially improve inadequate
      antiretroviral dosing in the treatment of HIV infection. Our objective was to
      review the evidence regarding TDM in HIV management. METHOD: We searched MEDLINE
      using the following key words: therapeutic drug monitoring, HIV infection,
      pharmacokinetics, antiretroviral therapy, protease inhibitors, antiretroviral
      naive, antiretroviral-experienced, and salvage therapy. inclusion criteria
      required definition of optimal concentration thresholds and measures of treatment
      effectiveness at these targets. RESULTS: Our search yielded 39 studies. 11
      studies met inclusion criteria. 4 studies compared efficacy of TDM to standard of
      care (SOC) interventions via randomized clinical trials and were grouped as
      "interventional." 7 studies retrospectively defined thresholds from observed
      differences in outcome and were grouped as "observational." 3 interventional
      studies targeted similar indinavir concentrations (Cmin = 0.10-0.15 mg/L). 2 of
      these studies increased achievement of target serum levels and percentages of
      undetectable viral load (23%-41%, p < or = .009) with TDM implementation.
      CONCLUSION: TDM can effectively target antiretroviral threshold concentrations
      and improve virologic suppression in some cases. Further work is needed to define
      plasma thresholds and assess the value of TDM in HIV management.

PMID- 16798622
TI  - Evaluation of Subcutaneous Proleukin (interleukin-2) in a Randomized
      International Trial (ESPRIT): geographical and gender differences in the baseline
      characteristics of participants.
AB  - BACKGROUND: ESPRIT, is a phase III, open-label, randomized, international
      clinical trial evaluating the effects of subcutaneous recombinant interleukin-2
      (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease
      progression and death in HIV-1-infected individuals with CD4+ T-cells > or =300
      cells/microL. OBJECTIVES: To describe the baseline characteristics of
      participants randomized to ESPRIT overall and by geographic location. METHOD:
      Baseline characteristics of randomized participants were summarized by region.
      RESULTS: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries.
      41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America,
      Asia, and Australia, respectively. The median age was 40 years, 81% were men, and
      76%, 11%, and 9% were Caucasian, Asian, and African American or African,
      respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and
      Argentina. Overall, 55% and 38% of the cohort acquired HIV through male
      homosexual and heterosexual contact, respectively. 25% had a prior history of
      AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and
      esophageal candida were most commonly reported. Median nadir and baseline CD4+ T
      cell counts were 199 and 458 cells/muL, respectively. 6% and 13% were hepatitis B
      or C virus coinfected, respectively. Median duration of antiretroviral therapy
      (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and
      the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART
      before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used
      ART from two or more ART classes, with 49% using a protease inhibitor-based
      regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based
      regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). CONCLUSION: ESPRIT
      has enrolled a diverse population of HIV-infected individuals including large
      populations of women and patients of African-American/African and Asian ethnicity
      often underrepresented in HIV research. As a consequence, the results of the
      study may have wide global applicability.

PMID- 16798624
TI  - Mood and anxiety disorders in widowhood: a systematic review.
AB  - The association between widowhood and mental health problems, such as depressive
      symptomatology and anxiety, has been examined extensively. Few studies, however,
      have explored the prevalence and incidence of mood and anxiety disorders based on
      diagnostic criteria after the loss of the partner. We conducted a systematic
      review, and searched major bibliographical databases for studies examining mood
      and anxiety disorders in widowhood. We included all studies examining the
      prevalence or incidence of mood and anxiety disorders in the widowed, according
      to diagnostic criteria as assessed with a structured diagnostic interview. Eleven
      studies were identified, exploring the prevalence and incidence of mood and
      anxiety disorders in 3,481 widowed individuals and 4,685 non-widowed controls. As
      expected, the prevalence of Major Depressive Disorder (MDD) and anxiety disorders
      were considerably elevated in widowed individuals, especially in the first year
      after the loss of a spouse. During the first year of bereavement, almost 22% of
      the widowed were diagnosed as having MDD; almost 12% met diagnostic criteria for
      Post Traumatic Stress Disorder; and there were higher risks of Panic Disorder and
      Generalized Anxiety Disorder. The incidence rate of MDD and several anxiety
      disorders ranged from 0.08-0.50. The relative risk of developing a mood or
      anxiety disorder ranged from 3.49-9.76, in the widowed, compared to control
      subjects.

PMID- 16798623
TI  - Concomitant use of an active boosted protease inhibitor with enfuvirtide in
      treatment-experienced, HIV-infected individuals: recent data and consensus
      recommendations.
AB  - Recent data from clinical trials investigating the efficacy of enfuvirtide, a
      fusion inhibitor, in treatment-experienced patients have revealed that the
      addition of enfuvirtide (ENF) to an active boosted protease inhibitor regimen
      doubles the rate of virological response. At week 48 of the TORO studies, 55% of
      patients previously naive to and receiving lopinavir/ritonavir (LPV/r) with ENF
      achieved a viral load of <400 copies/mL compared with 24% of patients treated
      with LPV/r alone. At week 24 of the RESIST studies, 70% of previously ENF-naive
      patients who took both ENF and tipranavir/ritonavir (TPV/r) achieved a >or=1
      log10 reduction in viral load compared with 37% of such patients treated with
      TPV/r alone. Similarly, concomitant use of TMC114/ritonavir (TMC114/r) with ENF,
      compared with TMC114/r alone, increased the number of patients with <50 copies/mL
      from 46% to 64% in a combined 24-week analysis from the POWER trials. Data from
      these trials suggest that combining one agent from a new class with a new agent
      from a previously exposed class offers a greater chance of achieving full
      virological control than either type of agent alone. Undetectable viraemia should
      be the primary objective for treatment-experienced patients requiring a switch in
      therapy, and the present data support the combination of an active boosted
      protease inhibitor with an agent from a new class (e.g., ENF) for triple-class
      experienced patients.

PMID- 16798625
TI  - Comparison of older depressed hospitalized patients with and without heart
      failure/pulmonary disease.
AB  - Test the hypothesis that depressed hospitalized patients with congestive heart
      failure (CHF) and/or chronic pulmonary disease (CPD) are no different from
      depressed patients with other medical disorders, and so can be treated similarly.
      Consenting patients aged 50 or over consecutively admitted to the medical
      services at Duke University Medical Center and three community hospitals were
      screened for depressive disorder using the Structured Clinical Interview for
      Depression (SCID-IV). Characteristics of patients reflecting vulnerability,
      stressors, and coping resources were assessed. CHF/CPD patients with major (n =
      413) and minor (n = 587) depression were compared to depressed patients with
      other medical disorders (n = 63). Among those with major depression, patients
      with CHF/CPD differed from those with other medical disorders in having less
      severe depression and less severe cognitive impairment, but greater physical
      illness severity. Among those with minor depression, CHF/CPD patients tended to
      be older and, as with major depression, had less severe depression and more
      severe medical illness. These findings were largely confirmed when CHF and CPD
      patients were examined separately. Depressive disorders in CHF/CPD patients are
      similar to those in patients with other medical disorders. However, they may be
      associated with less severe depressive symptoms and more severe physical illness
      than depressed patients with other medical disorders. These findings help to
      identify the unique ways in which depressive disorder manifests itself in
      hospitalized patients with chronic heart and lung disease that may impact their
      management.

PMID- 16798626
TI  - Streamlined models of dementia care mapping.
AB  - Dementia Care Mapping (DCM) is an observational tool that provides rich data
      about the quality of life and quality of care of persons with dementia in group
      care settings. The method is time-consuming and thus costly to implement in
      practice. This paper presents an attempt to 'streamline' DCM for the sake of
      simplifying it and reducing the financial resources required to implement it.
      Data were collected for 166 persons with dementia in three types of care
      settings. Seven streamlined time-sampling models were tested against the original
      DCM model. In general, results support the use of certain models for specific
      purposes. The strengths and limitations of these streamlined models are discussed
      and recommendations are made.

PMID- 16798627
TI  - Post-acute dispositions of older adults hospitalized for depression.
AB  - This study addressed factors associated with six-month post-acute dispositions
      (continuous community stay, medical hospitalization, psychiatric
      rehospitalization, nursing home placement, death) for older adults hospitalized
      for depression and discharged to the community. The sample included 199 older
      adults; and data were collected via medical records, interviews with discharge
      planners, patients, and family members. Over half of the sample remained in the
      community throughout the observation period; 23% experienced psychiatric re
      admission and 10% entered a nursing home. Several factors associated with nursing
      home placement were identified: less improvement in depression during the
      hospitalization, lower Global Assessment of Functioning (GAF) scores at
      discharge; and less mental health service use in the post-acute period. Those at
      higher risk of psychiatric re-admission had more previous psychiatric
      hospitalizations and were marginally more likely to be married and have lower
      Brief Psychiatric Rating Scale (BPRS) scores at discharge. Differentiating those
      at risk for nursing home placement may be easier than differentiating those at
      risk of psychiatric readmission.

PMID- 16798628
TI  - Relationship between anxiety and agitation in dementia.
AB  - Anxiety and agitation are common in people with dementia. Their consequences can
      be severe, including increased mortality rates and institutionalization. Despite
      the importance of these symptoms there is little literature in this area. Some
      studies have assumed that agitation is the outward manifestation of anxiety,
      while others have attempted to differentiate between them. The aim of this study
      was to investigate the relationship between anxiety and agitation in people with
      mild-to-moderate dementia. A secondary aim was to compare two measures of anxiety
      which have been used in people with dementia. A cross-sectional correlation
      design was used. Participants were 40 older adults with dementia. Agitation,
      anxiety, depression, and level of cognitive impairment were measured. The main
      finding from the study was that anxiety and agitation are associated in dementia.
      The degree of correlation did not support the use of agitation as a measure of
      anxiety. Anxiety symptoms of autonomic sensitivity were not correlated with
      agitation and could be used to differentiate between the two if this was
      required. The use of the Rating for Anxiety in Dementia (RAID) was supported as a
      measure of anxiety in people with dementia.

PMID- 16798629
TI  - Predicting mental health outcomes in female working carers: a longitudinal
      analysis.
AB  - This study investigated the factors contributing to psychological distress and
      positive affect over time in female working carers of older people.
      Questionnaires (including measures of work-related, care-related, interpersonal
      and psychological aspects of working and caring) were distributed to 275 female
      working carers in the UK, the majority of whom were working as nurses in the
      National Health Service. In cross-sectional analyses, higher work stress and work
      demands predicted higher psychological distress among respondents. Better carer
      health, lower external pressures to care and higher work satisfaction predicted
      greater positive affect. The combined effects of greater work stress and work
      demands also predicted higher levels of psychological distress at follow-up
      (after one year), whereas younger age and lower work stress predicted greater
      positive affect over time. We conclude that more stressful and demanding work
      roles appear detrimental to carers' mental health, while lower stress
      occupational roles may be beneficial, providing satisfaction and fulfilment
      outside of the caring role. Older female carers may be especially at risk of
      psychological distress, possibly due in part to increasing health problems of
      their own.

PMID- 16798630
TI  - Factors related to medication adherence in memory disorder clinic patients.
AB  - Medication adherence is a substantial problem in the elderly. It may be even more
      important among elderly persons with memory problems, since other factors that
      lead to non-adherence may be compounded with the memory problems themselves. The
      objective was to determine whether a model that integrates research on medication
      adherence from several research domains is useful in understanding adherence in
      elderly patients. The methodology involved a cross-sectional observational study
      using a convenience sample of 63 patients drawn from a university-affiliated
      outpatient memory disorders clinic. The primary measure of medication adherence
      was caregivers' reports of patients' medication adherence. Patients and their
      caregivers were asked questions assessing their beliefs about the seriousness of
      each condition for which a medication was prescribed and the likely outcome of
      that condition without treatment. Additional data collected included presence of
      side effects, total number of medications taken, and patients' mood and cognitive
      status. Multilevel path analysis confirmed several model-based predictions.
      Caregivers' reports of adherence were predicted by estimates of disease outcome,
      the presence of side effects, and patients' relying on themselves to remember to
      take medications. Results partially confirm the integrative model in
      understanding medication adherence in these patients. Patients' beliefs about the
      likely effect of medication treatment for their condition and the presence of
      side effects influence reported medication adherence. Results thus suggest that
      efforts to educate patients about the likely response of their medical condition
      to treatment and to assess and deal with medication side effects might improve
      patient adherence.

PMID- 16798631
TI  - Depression and mental health among older Mexican American spouses.
AB  - Although the association between marriage and well-being is well established, few
      studies have focused on learning more about the context of marriage and mental
      health. Recent research studying the mechanisms of marriage and health has
      focused on contagion of well-being among spouses. This study examined the
      association of depression with self-esteem, social support, life satisfaction,
      concern for independence, and cognitive function using baseline data for 553
      older, Mexican American couples. Overall, we found evidence to suggest an
      interdependent relationship between husbands' and wives' emotional states, but
      the association was not equal for couples. Husbands' depression was significantly
      associated with the well-being of their wife, but the wife's depression was
      rarely associated with the husband's well-being. The findings from this study add
      to the increasing literature on spousal contagion by focusing on an under studied
      minority group, examining how depression affects well-being, and highlighting
      unequal effects of marriage on spousal well-being.

PMID- 16798632
TI  - Analysis of a care planning intervention for reducing depression in older people
      in residential care.
AB  - Approximately 40% of older people in residential care have significant symptoms
      of depression. A training and care-planning approach to reducing depression was
      implemented for 114 depressed residents living in 14 residential care homes in
      North Yorkshire, UK. Care staff were offered brief mental health training by
      community mental health teams for older people. They were then assigned to work
      individually with residents in implementing the care-planning intervention, which
      was aimed at alleviating depression and any health, social or emotional factors
      that might contribute to the resident's depression. Clinically significant
      improvements in depression scores were associated with implementation of the care
      planning intervention as evidenced by changes in scores on the Geriatric Mental
      State Schedule-Depression Scale. There was evidence of an interaction between the
      power of the intervention and degree of dementia. These improvements were not
      accounted for by any changes in psychotropic medication. The training was highly
      valued by care staff and heads of homes, and they considered that the care
      planning intervention represented an improvement in quality of care for all
      residents, irrespective of levels of dementia. Staff also reported improvements
      in morale and increased confidence in the caring role as a result of their
      participation. The limitations of this study are discussed. On the basis of a
      growing body of evidence, it is argued that there is an urgent need for a
      suitably powered randomised controlled trial and economic evaluation, to test the
      cost-effectiveness of personalised care planning interventions aimed at reducing
      depression in older people in residential care.

PMID- 16798633
TI  - Effects of teaching resourcefulness skills to elders.
AB  - The objective of this study was to examine the effects of learned resourcefulness
      training (LRT) on health of elders in retirement communities (RCs). In a clinical
      trial, 46 elders in four randomly selected RCs received resourcefulness training
      and were compared to 43 elders in four RCs who participated in a focused
      reflection reminiscence (FRR) group. The two groups were similar at baseline.
      Repeated measures analysis of variance revealed no changes on anxiety or
      depression over time; however, both were significantly correlated with functional
      status (r's = 0.29 and 0.35, p's < 0.01), self-assessed health (r's = -0.18 and 
      0.26, p's < 0.05), and resourcefulness (r's = -0.24 and -0.21, p's < 0.05).
      Although main effects for group were not significant, interaction effects of
      group and time on self-assessed health and functional status were found. These
      findings suggest that although teaching resourcefulness to groups of elders in
      RCs may have beneficial effects on improving their perception of health and
      functioning over time, significant effects on mental health may not be apparent.

PMID- 16798634
TI  - Subjective memory beliefs and cognitive performance in normal and mildly impaired
      older adults.
AB  - Previous research suggests that subjective perceptions of memory may be related
      to objective memory performance. In the present study, healthy community-dwelling
      elders (N = 73, mean age = 75.25 years, education = 16.2 years) completed a
      neuropsychological assessment, including two questionnaires of subjective memory
      beliefs. Each participant was identified, via consensus conference, as belonging
      to either an amnestic mild cognitive impairment (MCI, n = 16) or no mild
      cognitive impairment (noMCI, n = 57) group. Results indicated that subjective
      memory capacity beliefs were significantly related to verbal memory performance
      in the MCI group, but not in the noMCI group. This differential relationship
      persisted even after controlling for depressive symptoms, and was not reflective
      of unequal variances in the two groups. Thus, results indicate that subjective
      memory beliefs may be better indicators of performance in those with possible
      incipient cognitive impairment than normal older adults, perhaps because persons
      with MCI have heightened insight into their memory functioning, and that this
      relationship is not due to group differences in depressive symptoms.

PMID- 16798635
TI  - Predictors of response to the 'Coping with Depression' course for older adults. A
      field study.
AB  - This field study explored the prognostic factors of the immediate and long-term
      effects of the Coping with Depression course for older adults (CWD). With the aim
      of both indicated as well as secondary prevention, the course is provided by the
      prevention departments of the community mental health care system in the
      Netherlands. A total of 317 course participants (age 55-85 years; 69% female)
      took part in this study; 41% had a major depressive disorder (MDD). A variety of
      demographic, clinical, psychosocial and treatment factors of possible relevance
      for indicated and secondary prevention were investigated. Random coefficient
      regression models and logistic regression models were used to examine their
      contribution to the immediate and maintenance effect. The course was beneficial
      for all participants, and the level of depression reached at the end of the
      course was maintained over the next 14-months. Current MDD, high levels of
      anxiety, less previous depressive episodes and more education predicted a larger
      benefit. However, the clinical significance of these predictors was too small to
      justify further triage. Further treatment should be considered for the
      participants with a post-treatment score >/=16. Group-membership was not a
      significant predictor of the variation in effect.

PMID- 16798637
TI  - Hb Marineo [beta70(E14)Ala-->Val]: a silent hemoglobin variant with a mutation
      within the heme pocket.
AB  - We report a new hemoglobin (Hb) variant, Hb Marineo [beta70(E14)Ala --> Val],
      found in three generations of a family from West Sicily. The mutation is due to a
      GCC --> GTC substitution at codon 70 of the beta-globin gene. To date, three
      mutations at codon 70 of the beta-globin gene have been described, presenting
      with hemolytic anemia. In our case, no anemia or other alteration of
      hematological indices were found. Cation exchange high performance liquid
      chromatography (HPLC) showed a peak in the P2 window (VARIANT I), while a peak
      was detected by VARIANT II HPLC in the P3 window. Reversed phase HPLC analysis
      showed an abnormal chain amounting to about 40% of the total beta chains.

PMID- 16798638
TI  - Three new alpha-thalassemia point mutations ascertained through newborn
      screening.
AB  - We report three new alpha-thalassemia (thal) point mutations detected during
      newborn screening for hemoglobinopathies. The first mutation is a single
      nucleotide deletion (-A) that abolishes the translation initiation codon of the
      alpha2-globin gene, detected in a newborn of Hmong ethnicity who carried the
      Southeast Asian alpha(0)-thal deletion (alpha(T)alpha/- -(SEA)). The second
      mutation, a frameshift caused by a single nucleotide deletion in exon 2 of the
      alpha1-globin gene [codon 78 (-C)], was detected in a Black/Chinese newborn who
      also carried the Southeast Asian alpha0-thal deletion (alphaalpha(T)/- -(SEA)).
      The third mutation was a frameshift in exon 3 of the alpha2-globin gene, codons
      113/114 (-C). This mutation was detected in a newborn who carried the 3.7 kb
      alpha(+)-thal deletion (alpha(T)alpha/-alpha(3.7)).

PMID- 16798639
TI  - A new alpha chain hemoglobin variant: Hb Al-Hammadi Riyadh [alpha75(EF4)Asp-->Val
      (alpha2)].
AB  - A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh
      [codon 75 (GAC-->GTC); alpha75(EF4)Asp-->Val (alpha2)] corresponding to an A-->T
      transversion on the second exon of the alpha2-globin gene, is described. The
      variant was characterized by DNA sequencing and mass spectrometry (MS). The
      variant was found during a routine Hb analysis for anemia in a 16-month-old boy
      who lived in Riyadh, Kingdom of Saudi Arabia.

PMID- 16798640
TI  - Secretory phospholipase A2 levels in patients with sickle cell disease and acute
      chest syndrome.
AB  - In a multicenter study (eight centers), we determined secretory phospholipase
      A(2) (sPLA(2)) levels in patients with sickle cell disease and acute chest
      syndrome (ACS). The diagnosis of ACS was made according to established criteria.
      The sPLA2 levels were determined in blood samples collected at baseline (time of
      diagnosis) and serially thereafter up to day 22-35 follow-up visits. Thirty-four
      of 43 (80%) patients with ACS had enzyme levels > or =1.00 AU at baseline. The
      enzyme levels decreased significantly on Days 2 through Days 25-35 after
      baseline. Nine of 43 (20%) patients had baseline sPLA2 values of <1.00 AU with
      six of them never exceeding 1.00 AU at any point in time during follow-up. The
      data indicate that the reliability of sPLA(2( for predicting the development of
      ACS is not perfect (100%) as was previously reported but occurs in about 80% of
      the patients.

PMID- 16798641
TI  - The codon 37 (TGG-->TAG) beta(0)-thalassemia mutation found in a Chinese family.
AB  - We have found an example of the nonsense beta-thalassemia (thal) mutation at
      codon 37 (TGG-->TAG; Trp-->Stop) in a Chinese family. The fetus, who inherited
      both parents' beta-thalassemic alleles, was a compound heterozygote for the
      codons 41/42 (-TCTT) and codon 37 (TGG-->TAG) mutations, and presented with the
      phenotype of severe beta-thal.

PMID- 16798642
TI  - Haplotypes linked to three rare beta-thalassemia mutations, originally reported
      in Tunisia.
AB  - The polymorphism of the beta-globin gene haplotypes and frameworks are useful in
      the determination of the unicentric and multicentric origin of a mutational
      event. In order to improve our knowledge of the chromosomal background of the
      beta-globin gene in three beta-thalassemia (thal) mutations originally reported
      in Tunisia, namely codons 25/26 (+T), codon 30 (G-->C) and IVS-I-2 (T-->G), we
      have investigated 13 unrelated individuals. There were five non transfusion
      dependent patients homozygous for the IVS-I-2 (T-->G) mutation, five others were
      homozygous for the codon 30 (G-->C) mutation, one was a homozygote for the codons
      25/26 (+T) insertion mutation and one patient was a compound heterozygote for the
      codon 39 (C-->T) and codon 25/26 (+T) mutations; the last patient had a
      betaS/codon 25/26 (+T) compound heterozygous genotype. Haplotype analysis was
      carried out by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) based methods. The framework polymorphism was established by direct
      sequencing. beta-Globin gene analyses demonstrated that all IVS-I-2 (T-->G) cases
      were associated with haplotype IX; the codon 30 (G-->C) mutation was supported by
      haplotype I, while the codons 25/26 (+T) mutation was linked to haplotypes I and
      IX.

PMID- 16798643
TI  - Iron mobilization from transferrin and non-transferrin-bound-iron by deferiprone.
      Implications in the treatment of thalassemia, anemia of chronic disease, cancer
      and other conditions.
AB  - Iron mobilization from transferrin is one of the most important screening methods
      for the selection of chelators intended for clinical use in the treatment of iron
      overload in thalassemia and other conditions. In vitro and in vivo screening of
      approved and experimental chelating drugs has shown that only the alpha
      ketohydroxypyridines deferiprone (L1) and 1-allyl-2 methyl-3-hydroxypyrid-4-one
      (L1NAll), are effective in the mobilization of iron from transferrin. Iron
      mobilization from transferrin and non-transferrin-bound-iron (NTBI) can be used
      to optimize existing chelation therapy protocols for the treatment of iron loaded
      patients. New chelation strategies involving L1 and its combination with
      deferoxamine (DFO) and other chelators can be used to increase iron excretion and
      reduce or prevent excess iron deposition in the heart and other vital organs of
      iron loaded patients by comparison to monotherapies. Deferiprone and its
      combinations may also have potential applications in the treatment of cancer, the
      anemia of chronic disease and other conditions.

PMID- 16798644
TI  - Radiation protection by deferiprone in animal models.
AB  - The effectiveness of deferiprone (L1) in removing depleted uranium (DU) and
      protecting animals from radiation exposure was examined. Rats that had received 2
      mg/kg DU via intramuscular injection were orally administered 100, 200 or 400
      mg/kg L1 for 3 days. In all of the groups, significant increases in urinary DU
      excretion and decreases in DU concentration in the injected muscle were observed,
      indicating that L1 combined with DU and DU was excreted in the urine. No
      significant increase in the amount of DU in the excreta or decrease in DU
      concentration in organs other than the muscles was found. As a preliminary test,
      the effectiveness of L1 in reducing radiation damage was examined in mice
      injected with 400 mg/kg L1 and rats administered orally with 200 and 400 mg/kg L1
      before and just after x-ray exposure. The results were inconclusive.

PMID- 16798645
TI  - Effect of deferiprone on liver iron overload and fibrosis in hepatitis-C-virus
      infected thalassemia.
AB  - To assess the effects of liver iron overload and fibrosis after treatment with a
      chelating agent in hepatitis C virus (HCV)-infected thalassemia, from April 1999
      to July 2004, 45 patients with thalassemia major (age range 9-33 years, mean
      19.3) received daily deferiprone (L1) for 23-60 months (75 mg/kg). The patients
      were divided into two groups on the basis of their hepatitis status (27 with, 18
      without). Their serum was analyzed for alanine aminotransferase (GPT), aspartate
      aminotransferase (GOT), bilirubin (total/direct), r-glutamyl transpeptidase (r
      GT), alkaline phosphatase (Alk-P), and ferritin. Liver iron overload and fibrosis
      were defined by a senior pathologist. No significant differences were
      demonstrated in serum levels of GPT, GOT, bilirubin, r-GT, Alk-P or ferritin;
      comparison was made for each group before and after L1 treatment. Iron scores
      were 2.3 +/- 0.9 and 2.8 +/- 0.9 for the hepatitis C negative and positive
      groups, respectively (p = 0.07), with liver fibrosis scores of 1.0 +/- 0.5 and
      0.4 +/- 0.52 (p = 0.56). The two scores were not higher for the positive group.
      There was no evidence of: 1) greater iron overload and fibrosis in the HCV
      infected thalassemic patients; 2) L1 inducing progressive hepatic fibrosis or
      worsening iron overload in HCV-infected thalassemic patients after long-term
      therapy; 3) further damage to liver cells associated with L1 treatment.

PMID- 16798646
TI  - Liver fibrosis and iron levels during long-term deferiprone treatment of
      thalassemia major patients.
AB  - Deferiprone (L1) is an orally active iron-chelation agent that is being evaluated
      as a treatment for iron overload in thalassemia major. Although some reports have
      concluded that LI may exacerbate hepatic fibrosis and the deterioration of liver
      function in thalassemia patients, other studies have reported no detrimental
      effects. In view of these serious concerns regarding the hepatic toxicity of LI,
      a Taiwanese group of beta-thalassemia (thal) patients with the longest known
      duration of LI therapy and who had provided liver biopsies, were enrolled in this
      study. From April 1999 to July 2004, the 17 enrolled thalassemia major patients
      had been on L1 therapy for as long as 19 to 60 months. Two liver biopsies from
      each of the 17 patients were received at the China Medical University Hospital,
      Taichung, Taiwan. Serum alanine aminotransferase (ALT), viral serological studies
      for hepatitis B and hepatitis C, iron scores and fibrosis scores were available
      at the beginning of the study and at the time of the second biopsy. Overall, the
      17 patients received L1 therapy continuously for a mean period of 3.3 years. With
      the exception of two patients, fibrosis scores decreased in all patients after LI
      therapy. Three patients had increased iron scores after therapy of L1 and 11
      patients had increased ALT levels; increased ALT levels occurred more frequently
      in hepatitis C positive patients. In this study, most thalassemia major patients
      had no progression of hepatic fibrosis or increased liver iron stores during long
      term LI therapy.

PMID- 16798647
TI  - Low serum ferritin levels are misleading for detecting cardiac iron overload and
      increase the risk of cardiomyopathy in thalassemia patients. The importance of
      cardiac iron overload monitoring using magnetic resonance imaging T2 and T2*.
AB  - The incidence of cardiomyopathy was monitored in a 6-year follow-up study
      involving 56 transfused thalassemia patients treated with deferoxamine (DFO),
      deferiprone (L1) or their combination. During this period, five female patients
      on regular subcutaneous or intravenous DFO presented with cardiac complications.
      Three patients suffered congestive heart failure and the other two arrhythmias.
      Four of the five patients maintained serum ferritin levels of about 1 mg/L or
      below and the fifth about 1.5 mg/L for several years prior to the cardiomyopathy.
      Cardiac magnetic resonance imaging (MRI) T2* and T2 was performed in four
      patients after the cardiomyopathy, identifying the presence of moderate-to-heavy
      siderosis. The treatment of the five patients has since changed, involving mainly
      the use of L1. Low serum ferritin levels appear to be misleading for detecting
      cardiac iron overload and this may increase the risk of cardiomyopathy. The MRI
      T2 and T2* relaxation time measurements are a more accurate method of detecting
      cardiac iron overload. Chelation therapy using L1 or appropriate L1/DFO
      combinations can reduce cardiac iron overload and the mortality rate in
      thalassemia patients.

PMID- 16798648
TI  - Regression of myocardial dysfunction after switching from desferrioxamine to
      deferiprone therapy in beta-thalassemia major patients.
AB  - This study tries to compare the cardioprotective effects of the desferrioxamine
      (DFO) and deferiprone (L1) therapies on thalassemia major patients. We enrolled
      nine patients with thalassemia major complicated by some degree of myocardial
      dysfunction. These patients, recipients of >10 years of DFO injection therapy,
      were switched from DFO to L1. Echocardiographic measures of left ventricular
      systolic, diastolic and global functions, were assessed regularly every 6 months.
      Mean values of each parameter for the DFO and L1 treatment periods were compared
      using paired t-test and Wilcoxon signed-rank test. Global cardiac function
      improved significantly. Myocardial dysfunction in patients with thalassemia major
      can be reversed by regular use of the oral iron chelator L1.

PMID- 16798649
TI  - Effective combination therapy of deferiprone and deferoxamine for the rapid
      clearance of excess cardiac IRON and the prevention of heart disease in
      thalassemia. The Protocol of the International Committee on Oral Chelators.
AB  - The International Committee on Oral Chelators (ICOC) combination therapy protocol
      involving the administration of deferiprone (L1) during the day (80-110
      mg/kg/day) and deferoxamine (DFO) (40-60 mg/kg at least 3 days/week) during the
      night for 8-12 hours using a pump, or the whole 24 hours using an elastomeric
      pump infuser, has been tested in 11 thalassemia patients (seven males, four
      females) over a period of 9-28 months. The patients had variable serum ferritin
      levels (0.54-4.6 mg/L) and cardiac iron load ranging from normal to severe
      siderosis levels (MRI T2*: 4.7-45 ms). There was a substantial overall reduction
      in serum ferritin levels (0.17-2.16 mg/L) and normalization of cardiac iron (MRI
      T2* >20 ms) in all patients. In two patients with severe and moderate cardiac
      iron load range levels, cardiac iron normalization was achieved within 9-10
      months. Two patients on L1 monotherapy (80-120 mg/kg/day) maintained normal range
      MRI T2* cardiac iron levels over the same period. The ICOC combination therapy
      protocol appears to be the most effective and least cumbersome form of chelation
      treatment for the rapid clearance of excess iron from the heart.

PMID- 16798650
TI  - Glutathione S-transferase M1 gene polymorphisms are associated with cardiac iron
      deposition in patients with beta-thalassemia major.
AB  - Patients with beta-thalassemia (thal) major are subject to peroxidative tissue
      injury by iron overload. Glutathione S-transferases work as antioxidants, and
      their activity is determined genetically. In this study, we used multiplex
      polymerase chain reaction (m-PCR) to analyze polymorphisms of two endogenous
      antioxidant agents, glutathione S-transferase M1 (GSTM1) and glutathione S
      transferase T1 (GSTT1), and to determine their roles in 41 patients with beta
      thal major. Our results showed that the GSTM1 and GSTT1 null genotypes were not
      associated with any incidence of endocrine dysfunction (including diabetes
      mellitus, hypogonadism, hypothyroidism, and growth hormone deficiency), liver
      function, or impaired left ventricular ejection fraction (LVEF). The GSTM1 null
      genotype, but not the GSTT1 null genotype, was associated with a decreased signal
      intensity ratio on cardiac magnetic resonance imaging (MRI). Our results suggest
      that genetic variations of the GSTM1 enzyme are associated with cardiac iron
      deposition in patients with beta-thal major.

PMID- 16798651
TI  - Comparison of oral and subcutaneous iron chelation therapies in the prevention of
      major endocrinopathies in beta-thalassemia major patients.
AB  - While hypertransfusion and subcutaneous iron chelation therapy have increased
      longevity of patients with beta-thalassemia (thal) major, endocrinopathies have
      become more common and impair the quality of their lives. Additionally,
      subcutaneous iron chelation therapy is an uncomfortable experience and can
      prevent patients from regular compliance with iron chelation therapy. We compared
      the efficacy of oral deferiprone (L1) to subcutaneous desferrioxamine (DFO)
      chelation therapy for the prevention of major endocrinopathies (growth hormone
      insufficiency, diabetes mellitus and gonadal dysfunction) among patients with
      beta-thal major to see if we could offer these patients an easier and more
      painless way to reduce their body iron load and related endocrine complications.

PMID- 16798652
TI  - A randomized controlled study evaluating the safety and efficacy of deferiprone
      treatment in thalassemia major patients from Hong Kong.
AB  - A controlled, open-label and randomized study was conducted to evaluate the
      safety and efficacy of the oral iron chelator deferiprone (L1) in thalassemia
      major patients from Hong Kong. Forty-nine patients were recruited in total
      (median age: 20 years; range: 8 to 40 years). The division of the patients was
      determined based on liver iron content and put into either the poorly-chelated
      (Group I) or well-chelated (Group II) groups. In Group I, 20 patients received
      combined therapy of L1 daily plus desferrioxamine (DFO), in a reduced frequency
      of twice weekly, while the control group consisted of 16 patients who were
      treated with DFO alone. In Group II, six patients received L1 only, while the
      control group consisted of seven patients treated with DFO alone. Only patients
      who participated for longer than 6 months were analyzed for efficacy (n = 44).
      The median study period was 18 months. Transient and mild gastrointestinal upset
      (31%), joint pain (15%) and liver enzyme elevation (23%) were the most common
      side effects noted for L1. No case of neutropenia was observed in this study.
      Serum ferritin (SF) levels showed significant decline in the poorly-chelated
      patients using combined therapy (L1 and reduced frequency DFO) as compared to
      those on DFO alone. However, their pre- and post-study liver iron content was not
      significantly different. Evaluation of the well-chelated group demonstrated no
      significant change in SF or liver iron content in both the study and control
      arms. We conclude that the short-term use of L1, with or without DFO, was safe
      and efficacious in our Chinese patient cohort. The long-term efficacy of reducing
      iron overload by treatment regimens including L1 requires further study.

PMID- 16798653
TI  - Thalassemia treatment and prevention in Uva Province, Sri Lanka: a public opinion
      survey.
AB  - Due to its excessive cost thalassemia management is a major health care problem
      in Sri Lanka. The majority of doctors are using only desferrioxamine (DFO), in
      grossly inadequate doses mainly because of its unavailability. Deferiprone (L1),
      which is more affordable, is not used due to fear of toxicity, as previously
      reported. Arthropathy attributed to L1 has been observed in some patients, and
      has led to the discontinuation of the drug in all patients, without scientific
      rationale. The proposed thalassemia prevention project for Uva Province is based
      on prevention of marriages between carriers. This could be achieved by carrier
      screening and counseling of teenagers and adolescents well before they select
      their partners. In Sri Lanka, people find their marriage partners at their work
      place or universities, by themselves, or with the help of professional marriage
      brokers (they are called Kapuwa), through relatives and close friends. This
      process of finding a partner may also be helped by paper advertisements. However,
      in addition to the appearance and attitude of the prospective partner, the caste,
      social background and horoscope are major considerations in selecting a partner.
      Even when they select partners on their own at the work place or university, they
      keep these factors in the back of their minds to ensure social acceptance. Many
      relationships are given up due to objections and advice from parents when the
      caste or social background does not match. A horoscope is a written document that
      almost every child gets, written by a professional horoscope reader and depending
      on the time of birth. It is believed, according to the horoscope, that a person's
      attitudes, desires, future prospects of finding a suitable partner, could be
      predicted. It is rare to proceed with a marriage if the horoscope does not match.
      These customs are considered less seriously among educated people when they find
      their partner at the work place or university. The concept of thalassemia risk
      free marriages advocates promotion of marriages where at least one partner is a
      non-carrier. Success of such a project could be monitored at the time of
      marriage. This opinion survey indicates that the public is motivated to promote
      carrier screening and the prevention of thalassemia.

PMID- 16798655
TI  - Pilot study on parental stress and behavioral adjustment to the thalassemia major
      disease process in children undergoing iron-chelation in western Taiwan.
AB  - Thalassemia was first described by Cooley and Lee in 1952 in several Italian
      children as a severe anemia with spleen and liver enlargement, skin
      discoloration, and bony changes. Great strides in management and intervention
      have not been matched by progress in psychosocial rehabilitation. Because
      parental stress and adaptation are of concern, this study focuses on parental
      stress and adjustment in response to the disease process of their afflicted
      children in western Taiwan. The parents of 18 thalassemia major patients (under
      12 years of age) were interviewed (in two sessions) to determine their feelings,
      sources of stress, and support during their childrens' disease process. The study
      found that: 1) many parents suffer from stress as a result of the disease
      process, 2) all parents had similar concerns about iron chelation treatment, and
      3) some resilience factors were present in the support system.

PMID- 16798654
TI  - Pilot study on the "quality of life" as reflected by psychosocial adjustment of
      children with thalassemia major undergoing iron-chelating treatment in western
      Taiwan.
AB  - Comprehensive care for thalassemia major (TM) patients has achieved great
      advances in the world, yet psychosocial developmental aspects of care in families
      with afflicted members has made only limited progress. Besides confronting the
      disease itself, a major task for children with TM is to develop into autonomous,
      healthy, and functioning adults. An emerging concept in considering the
      adjustment of children with chronic physical disorders is "quality of life"(QL).
      To study the QL with regard to reflection by psychosocial adjustment in TM
      children, we enrolled 55 TM patients undergoing intravenous (IV) and/or oral iron
      chelation, 39 of whom completed the content on issues related to QL according to
      Cramer and Devinsky. It was concluded that oral iron chelation can be better
      adjusted than IV iron chelation for a thalassemic child. This favors its use, but
      not necessarily in combination with IV iron chelation. Perception gaps that arise
      from age or generation merit concern. This approach to the study of QL, as
      reflected by psychosocial adjustment in children with TM, is an excellent method
      for learning about parental-child adjustment regarding a chronic physical
      condition such as TM.

PMID- 16798656
TI  - Iron-chelating and free-radical scavenging activities of microwave-processed
      green tea in iron overload.
AB  - Secondary iron overload is found in beta-thalassemia (thal) patients because of
      increased dietary iron absorption and multiple blood transfusions. Excessive iron
      catalyzes free-radical generation, leading to oxidative damage and vital organ
      dysfunction. Non-transferrin-bound iron (NTBI) detected in thalassemic plasma is
      highly toxic and chelatable. Though used to treat iron overload, desferrioxamine
      (DFO) and deferiprone (L1) also have adverse effects. Green tea (GT) shows many
      pharmacological effects, particularly antioxidative and iron-chelating
      capacities. This study was performed to investigate the ability of GT extracts to
      reduce plasma NTBI concentration and oxidative stress in vitro. The Fe(3+) was
      found to bind to GT crude extract and form a complex. Green tea crude extract
      time- and dose-dependently decreased plasma NTBI concentration and counteracted
      the increase of oxidative stress in both Fe(2+)-EDTA-treated human plasma and
      erythrocytes. Green tea is a bifunctional natural product that could be relevant
      for management of iron overload and oxidative stress.

PMID- 16798658
TI  - High blood pressure--disease or risk factor?

PMID- 16798657
TI  - Future chelation monotherapy and combination therapy strategies in thalassemia
      and other conditions. comparison of deferiprone, deferoxamine, ICL670, GT56-252,
      L1NAll and starch deferoxamine polymers.
AB  - Deferiprone (L1), and appropriate combinations with deferoxamine (DFO), can be
      used effectively for the treatment of thalassemia and other transfusional iron
      loading conditions. A number of experimental iron chelators such as deferasirox
      or ICL670 or Exjade (4-(3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl)-benzoic
      acid), deferitrin (4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methylthiazole-4 (S)
      carboxylic acid) or GT56-252, 1-allyl-2-methyl-3-hydroxypyrid-4-one or L1NAll and
      starch DFO polymers, are under clinical evaluation. ICL670 is the most advanced
      in development and appears to be effective in reducing liver iron in some
      patients but is overall ineffective in causing negative iron balance. It is also
      suspected that it is not effective in cardiac iron removal. Combination therapies
      using L1, DFO and new iron chelating drugs may cause higher efficacy and lower
      toxicity by comparison to monotherapies. However, several limitations including
      the high cost of the new chelating drugs may not facilitate the availability of
      these new treatments to the vast majority of thalassemia patients, most of whom
      live in developing countries.

PMID- 16798659
TI  - Atrial fibrillation surgery--a dedicated approach is the key to success. In-my
      opinion.

PMID- 16798660
TI  - High mortality rates in conservatively managed patients with acute coronary
      syndrome.
AB  - OBJECTIVES: The revised diagnostic criteria for the acute coronary syndrome (ACS)
      have created the need for accurate and representative data on treatment and
      outcome for the three categories of ACS. DESIGN: Consecutive patients admitted
      with a suspected ACS (n = 755) from February 1, 2003 to January 31, 2004 was
      registered and categorised into five diagnostic groups: 1) ST-elevation
      myocardial infarction (STEMI) (n = 126), 2) Non-ST-elevation myocardial
      infarction (NSTEMI) (n = 185), 3) Unstable angina pectoris (UAP) (n = 55), 4)
      Coronary heart disease (CHD) without ACS (n = 164) and 5) Non-coronary chest pain
      (n = 225). RESULTS: All-cause one-year mortality rates were 20%, 32%, 7%, 10% and
      3%, in patients with STEMI, NSTEMI, UAP, CHD without ACS and non-coronary chest
      pain, respectively. In patients with STEMI, 61% received immediate reperfusion
      therapy (ratio thrombolysis: primary PCI = 18:1). Only 3% of those with NSTEMI
      had PCI within two days. CONCLUSION: In this conservatively managed population of
      consecutive patients with ACS, the one-year mortality rate is significantly
      higher than seen in most registries and clinical trials.

PMID- 16798661
TI  - Association between glycometabolic status in the acute phase and 21/2 years after
      an acute coronary syndrome.
AB  - OBJECTIVES: To evaluate the association between glycometabolic status in the
      acute phase and 21/2 years later in patients with acute coronary syndrome (ACS).
      METHODS: Non-diabetic patients (n = 762) presenting with ACS were prospectively
      followed up for 21/2 years. Patients were stratified by admission plasma glucose
      (<6.1 mmol/l, 6.1 - 6.9 mmol/l and >or=7.0 mmol/l) and HbA1c (<or=4.5%, 4.6 -
      5.4% and >or=5.5%). The predictive value of glucose levels >or= 7.0 mmol/l and
      HbA1c >or= 5.5% for glycometabolic disturbance (i.e. diabetes or impaired fasting
      glycaemia (IFG)) was analysed. RESULTS: Of 762 patients, 13% had a diagnosis of
      diabetes and 16% had IFG at follow-up. The prevalence of glycometabolic
      disturbance at follow-up increased with increasing plasma glucose at admission,
      from 19% in patients with < 6.1 mmol/l to 42% in patients with >or= 7.0 mmol/l.
      Sixty-one percent of patients with HbA1c >or= 5.5% had glycometabolic disturbance
      after 21/2 years compared to only 25% of those with HbA1c < 5.5%. CONCLUSION: Non
      diabetic patients with ACS and hyperglycaemia are at high risk for developing
      glycometabolic disturbance. HbA1c may be an even stronger predictor of
      glycometabolic disturbance than plasma glucose.

PMID- 16798662
TI  - Incidence and outcome of atrial fibrillation in stable symptomatic coronary
      disease.
AB  - OBJECTIVES: Evaluate the prevalence, incidence and impact on prognosis of
      existing and new onset atrial fibrillation (AF) in patients with stable,
      symptomatic coronary artery disease. DESIGN: Data from the 7 665 participants
      included in the ACTION (A Coronary disease Trial Investigating Outcome with
      Nifedipine GITS) trial was used. RESULTS: Over a mean follow-up of 4.9 years, the
      incidence of recurrent AF in patients with AF at baseline (4.1%) was 13.5/100
      patient-years and 1.64/100 patient-years for patients without baseline AF.
      Patients with AF at baseline had increased mortality and new overt heart failure.
      New onset AF was associated with increased morbidity and mortality and in
      particular soon after onset. [adjusted 30-day relative risk for mortality 23, 95%
      CI 14-36; for debilitating stroke 37, 95% CI 18-77; and for heart failure 54, 95%
      CI 32-93]. The incidence of AF was not affected by treatment with nifedipine
      GITS. CONCLUSION: The presence of AF in patients with stable symptomatic CAD is
      an independent risk factor and in particular in the first 30 days for subsequent
      mortality and morbidity.

PMID- 16798663
TI  - Effects of celiprolol and simvastatin on the calculated risk of coronary heart
      disease (the Celisimva study).
AB  - OBJECTIVES: The most important risk factors for coronary heart disease are
      hypercholesterolemia, smoking and hypertension. To find out which treatment is
      more effective in modifying the total risk--lowering cholesterol concentration or
      using antihypertensive treatment--we conducted a parallel group placebo
      controlled study. The goal of the study was to assess the effect of two drugs on
      the calculated CHD Framingham risk score in subjects with both moderate
      hypertension and moderate hypercholesterolemia. DESIGN: Celiprolol for
      hypertension and simvastatin for cholesterol-lowering were given as monotherapy
      or as combination treatment. The effects of the treatments on the CHD risk scores
      were calculated after 3 months. A total of 112 patients were randomized. RESULTS:
      The total CHD risk decreased in simvastatin and combination groups from 26% to
      19% and from 26% to 17%, respectively. Celiprolol alone decreased the risk from
      25% to 21%, which was not statistically different from placebo. CONCLUSIONS: It
      can be concluded that subjects with moderate hypercholesterolemia and
      hypertension benefit more from lipid-lowering treatment with simvastatin than
      from blood pressure-lowering with beta blocker celiprolol.

PMID- 16798664
TI  - Impact of hypertension on left ventricular hypertrophy regression and exercise
      capacity in patients operated for aortic valve stenosis.
AB  - OBJECTIVES: To assess the influence of concomitant hypertension on left
      ventricular hypertrophy regression and exercise capacity in patients operated for
      aortic stenosis. DESIGN: We performed echocardiography 1 week, 6- and 18-month
      postoperatively in 78 patients, aged 70 (28-86) years, who received Medtronic
      Hall (33), Biocor (8), Carpentier-Edwards S.A.V. (14) and Freestyle (23)
      prosthetic valves for severe aortic stenosis. Forty nine patients participated in
      treadmill tests with ergospirometry at the 6- and 18-month visits. RESULTS: Left
      ventricular mass index was comparably reduced in normotensive and hypertensive
      patients (34 vs. 40 g/m2 after 6 months, and 43 vs. 46 g/m2 after 18 months, ns).
      In multiple regression analysis, adjusting for baseline left ventricular mass
      index, larger reduction in left ventricular mass index was associated with
      younger age and having a Freestyle prosthesis, but not with gender or history of
      hypertension (multiple R2=0.68, p < 0.05). Exercise capacity assessed as peak
      oxygen uptake increased from early to late evaluation in normotensive patients
      (VO2max 24.27 vs. 27.08 ml/kg/min, p < 0.05) while remained unchanged in
      hypertensive patients (VO2max 22.2 vs. 21.1 ml/kg/min). In multiple regression
      analysis, higher improvement in exercise capacity was predicted by male gender,
      younger age and absence of hypertension, while no independent association was
      found with Freestyle prosthesis (multiple R2 = 0.37, p < 0.05). CONCLUSIONS: In
      patients operated for aortic stenosis, concomitant hypertension is associated
      with lack of improvement in exercise capacity in spite of early left ventricular
      hypertrophy reduction comparable to what is found in normotensive patients.

PMID- 16798665
TI  - Thoracic aorta--dilated or not?
AB  - OBJECTIVES: Knowledge of normal aortic diameters is important in the assessment
      of aortic disease. The aim of this study was to determine normal thoracic aortic
      diameters. DESIGN: 77 patients undergoing computed tomography of the thorax were
      studied. The diameter of the thoracic aorta was measured at three levels in the
      ascending aorta and at three levels in the descending aorta. The diameter was
      studied in relation to age, sex, weight and height. RESULTS: We found that aortic
      diameter is increasing with increasing age. Even sex and BMI influence the aortic
      diameter but to a lesser extent than age. The upper normal limit for ascending
      aorta can be calculated with the formula D(mm) = 31 + 0.16*age and for descending
      aorta with the formula D(mm) = 21 + 0.16*age. Thus a 20-year-old person has an
      upper normal limit for ascending aorta of 34 mm and an 80-year-old person has a
      limit of 44 m. CONCLUSIONS: The thoracic aortic diameter varies with age, sex and
      body weight and height. The strongest correlation can be seen with age. Age
      should therefore be taken into consideration when determining whether the
      thoracic aorta is dilated or not.

PMID- 16798666
TI  - High mortality after coronary bypass surgery in patients with high-grade left
      main coronary artery stenosis.
AB  - OBJECTIVE: To determine mortality after coronary artery bypass grafting (CABG) in
      relation to degree of left main coronary artery (LMCA) obstruction. DESIGN: All
      patients without LMCA stenosis (n=3370), with low-grade stenosis (n = 261), high
      grade stenosis (n = 224) or total occlusion of the LMCA (n = 15) were followed
      for ten years after CABG performed during 1970-1989. RESULTS: Early mortality was
      1.9% and 2.3%, respectively, if there was no or a low-grade LMCA stenosis vs.
      6.3% if the stenosis was high-grade. Ten-year survival was 76% if no LMCA
      obstruction, 74% if low-grade stenosis and 64% if the stenosis was high-grade.
      Risk of early death (odds ratio 2.6, 95% CI 1.4-4.8) and mortality at ten years
      (relative risk 1.5, 95% CI 1.1-2.0) was higher in patients with high-grade
      stenosis than in those without LMCA stenosis. There was no increased long-term
      mortality in patients with low-grade stenosis or among the few patients with
      occlusion of the LMCA. CONCLUSIONS: High-grade LMCA stenosis was associated with
      a three-fold increased risk of early and fifty percent higher risk of late death
      than in patients without LMCA stenosis.

PMID- 16798667
TI  - Evaluation of myocardial metabolism with microdialysis after protection with cold
      blood- or cold crystalloid cardioplegia. A porcine model.
AB  - OBJECTIVES: There has been a considerable change in the patient population
      referred for cardiac surgery in the last decade. More complex and marginal
      patients require optimized myocardial protection. An insufficient cardioplegic
      procedure results in anaerobic metabolism during cardiac arrest with subsequent
      lactate accumulation. Increased lactate level is regarded as a predictor for low
      cardiac output syndrome. In an acute porcine model we examined two standard
      cardioplegic methods. Myocardial microdialysis was used to investigate the
      metabolism during cardioplegic arrest and in the reperfusion period. METHODS:
      Twelve domestic pigs were randomly chosen to receive either cold blood-or cold
      crystalloid cardioplegia. After midline sternotomy two microdialysis probes were
      implanted in two different regions of the heart. Cardiopulmonary bypass was
      initiated, aorta was clamped, and antegrade cardioplegia was delivered. These
      conditions were maintained for 90 min. Subsequent to myocardial reperfusion the
      animals were observed for 180 min. Microdialysis and plasma markers to
      characterize myocardial metabolism, and plasma markers for myocardial failure and
      necrosis were obtained every 30 min. RESULTS: Lactate concentrations were
      significantly increased in the cold crystalloid cardioplegia group compared to
      the cold blood cardioplegia group, in tissue dialysate (p < 0.001) as well as in
      serum (p = 0.018). Pyruvate concentrations in the dialysate were significantly
      increased in the cold crystalloid cardioplegia group compared to the cold blood
      cardioplegia group (p = 0.008). There were no significant differences in
      dialysate concentrations of glycerol. Plasma markers for myocardial failure
      (Brain Natriuretic Peptide) and for myocardial necrosis (Cardiac Troponin T)
      showed no differences between the groups. CONCLUSION: The results indicate that
      cold blood cardioplegia offers superior protection of the heart, in terms of more
      rapid normalization of myocardial metabolism. The microdialysis technique seems
      to have a high sensitivity and ability to detect even minor metabolic changes.
      This enhances the possibility of designing a myocardial protection, which might
      lower morbidity and mortality risk.

PMID- 16798668
TI  - Autotransfusion with cell saver for off-pump coronary artery bypass surgery: a
      randomized trial.
AB  - OBJECTIVES: Off-pump coronary surgery reduces transfusions, however, many
      patients still receive blood. This trial aims to clarify the effect of using a
      cell saver intraoperatively. DESIGN: In 60 patients shed blood was collected in
      the cell saver reservoir intraoperatively; randomization and processing or
      discharge were performed immediately after surgery. PRIMARY OUTCOME MEASURES:
      proportion of patients receiving allogeneic blood, and average number of units
      per patient. SECONDARY OUTCOME MEASURES: blood loss, hemoglobin levels,
      complications, and costs. RESULTS: Cell saver group versus control group;
      received transfusions: 17/30 vs. 14/29 (p = 0.28), allogeneic units: median 1
      (interquartile range 0 - 2) vs. 2 (IQR 0 - 7) (p = 0.06), intraoperative net
      blood loss: median 300 ml (IQR 193 - 403) vs. 610 ml (IQR 450 - 928) (p < 0.001).
      Control group patients had more complications leading to transfusion. Hemoglobin
      levels and costs were comparable between groups. CONCLUSIONS: Use of cell saver
      reduced intraoperative net blood loss and seemed to reduce transfusions by 1 unit
      per patient, however, this was probably attributable to more complications
      leading to transfusion in the control group. In the future larger trials are
      necessary.

PMID- 16798670
TI  - Lack of association of herpesviruses with brain tumors.
AB  - Gliomas are the most frequent primary brain tumors in humans. Many studies have
      been carried out on their etiology; however, the only confirmed risk factors are
      hereditary predisposing conditions and high dose of ionizing radiation. Recently,
      human cytomegalovirus (HCMV) gene products and nucleic acids were reported to be
      present in all of 27 glioma samples investigated in contrast to other brain
      tissues, and it was hypothesized that HCMV might play a role in glioma
      pathogenesis. To evaluate these findings, samples of 40 gliomas, 31 meningiomas,
      and 6 acoustic neurinomas (ACNs) were analyzed for the presence of HCMV
      macromolecules using polymerase chain reaction (PCR) and immunohistochemistry.
      Additionally, corresponding blood samples from 72 patients were analyzed for the
      presence of HCMV DNA to check for a possible contamination of tumor tissues with
      HCMV-infected blood cells. No HCMV DNA sequences were found, neither in brain
      tumor tissues nor in corresponding blood samples. Immunohistochemistry did not
      detect HCMV-specific proteins. Addressing a possible role of other herpesviruses
      as has been suggested in seroepidemiological studies, seroprevalence of
      antibodies to HCMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), and
      varicella-zoster virus (VZV) were determined by enzyme-linked immunosorbent assay
      (ELISA). Serological analyses of brain tumor patients showed no significant
      differences in the prevalences of antibodies to HCMV, HSV, EBV, or VZV compared
      to the general population. Thus, the data of the present study do not support the
      hypothesis of an association of herpesviruses with the development of primary
      brain tumors.

PMID- 16798669
TI  - Simian immunodeficiency virus envelope compartmentalizes in brain regions
      independent of neuropathology.
AB  - Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) gp160s
      obtained from the brain are often genetically distinct from those isolated from
      other organs, suggesting the presence of brain-specific selective pressures or
      founder effects that result in the compartmentalization of viral quasi-species.
      Whereas HIV has also been found to compartmentalize within different regions of
      the brain, the extent of brain-regional compartmentalization of SIV in rhesus
      macaques has not been characterized. Furthermore, much is still unknown about
      whether phenotypic differences exist in envelopes from different brain regions.
      To address these questions, env DNA sequences were amplified from four SIVmac239
      infected macaques and subjected to phylogenetic and phenetic analysis. The
      authors demonstrated that sequences from different areas of the brain form
      distinct clades, and that the long-term progressing macaques demonstrated a
      greater degree of regional compartmentalization compared to the rapidly
      progressing macaques. In addition, regional compartmentalization occurred
      regardless of the presence of giant-cell encephalitis. Nucleotide substitution
      rates at synonymous and nonsynonymous sites (ds:dn rates) indicated that positive
      selection varied among envelopes from different brain regions. In one macaque,
      envelopes from some but not all brain regions acquired changes in a conserved CD4
      binding motif GGGDPE at amino acids 382 to 387. Furthermore, gp160s with the
      mutation G383E were able to mediate cell-to-cell fusion in a CD4-independent
      manner and were more susceptible to fusion inhibition by pooled plasma from
      infected macaques. Reversion of this mutation by site-directed mutagenesis
      resulted in reduction of CD4-independence and resistance to fusion inhibition in
      cell fusion assays. These studies demonstrate that SIV evolution within the brain
      results in a heterogeneous viral population with different phenotypes among
      different regions.

PMID- 16798672
TI  - Persistent infection of RAW264.7 macrophages with the DA strain of Theiler's
      murine encephalomyelitis virus: An in vitro model to study viral persistence.
AB  - Theiler's murine encephalomyelitis virus (TMEV) is a member of the Picornaviridae
      family and causes a virus strain dependent pathology in the central nervous
      system of mice. The GDVII strain induces an acute and mostly fatal
      encephalomyelitis. In the few mice that survive, the virus is cleared by the
      immune system. In contrast, infection with the DA strain leads to a persistent
      infection, marked by inflammation and demyelination that resembles multiple
      sclerosis. In the DA-induced disease, macrophages play a crucial role because
      they contribute to demyelination by the secretion of toxic mediators. Moreover,
      they represent the main viral reservoir, hereby also underlining their essential
      role in TMEV persistence. The mechanism of this persistence is not yet understood
      and tools to investigate it directly, without the complexity imposed by
      experimental animals, are largely missing. By studying TMEV infection of RAW264.7
      macrophages, we found that the DA strain establishes a persistent infection in
      these cells, in contrast to the neurovirulent GDVII strain. Whereas the GDVII
      strain was cleared within 4 to 5 days post infection, DA virions were still
      present after 1 year of cell cultivation. This persistently DA-infected
      macrophage cell line, which we have called DRAW, provides a model to investigate
      the interactions between the cellular and viral factors influencing persistence
      and to screen for anti-TMEV agents.

PMID- 16798671
TI  - Relationship of antiretroviral treatment to postmortem brain tissue viral load in
      human immunodeficiency virus-infected patients.
AB  - Human immunodeficiency virus (HIV)-1 invades the central nervous system (CNS)
      soon after infection and is partially protected there from host immunity and
      antiretroviral drugs (ARVs). Sanctuary from highly active antiretroviral therapy
      (HAART) in the CNS could result in ongoing viral replication, promoting the
      development of drug resistance and neurological disease. Despite the importance
      of these risks, no previous study has directly assessed HAART's effects on brain
      tissue viral load (VL). The authors evaluated 61 HIV-infected individuals for
      whom both histories of HAART treatment and postmortem brain tissue VL
      measurements were available. Two groups were defined based on HAART use in the 3
      months prior to death: HAART(+) subjects had received HAART, and HAART(-)
      subjects had not received HAART. HIV RNA was quantified in postmortem brain
      tissue (log10 copies/10 microg total tissue RNA) and antemortem plasma (log10
      copies/ml) by reverse transcriptase-polymerase chain reaction (RT-PCR). Brain
      tissue VLs were significantly lower among HAART(+) subjects compared to HAART(-)
      subjects (median 2.6 versus 4.1; P= .0007). These findings suggest that despite
      the limited CNS penetration of many antiretroviral medications, HAART is at least
      partially effective in suppressing CNS viral replication. Because some HAART
      regimens may be better than others in this regard, regimen selection strategies
      could be used to impede CNS viral activity, limit neuronal dysfunction, and
      prevent or treat clinical neurocognitive disorders in HIV-infected patients.
      Furthermore, such strategies might help to prevent the development of ARV
      resistance.

PMID- 16798673
TI  - Characterization of lymphocytic infiltrates in progressive multifocal
      leukoencephalopathy: co-localization of CD8(+) T cells with JCV-infected glial
      cells.
AB  - We characterized inflammatory infiltrates in archival brain biopsy and autopsy
      samples from 26 HIV(+) and 20 HIV(-) patients with progressive multifocal
      leukoencephalopathy (PML). The predominant inflammatory cells were CD8(+) T
      lymphocytes. We defined CD8(+) T cell distribution with regard to JCV-infected
      glial cells, PML lesions and the extent of demyelination. In most samples from
      either HIV(+) and HIV(-) patients, we found positive correlations between the
      parenchymal CD8(+) T cells and JCV-infected glial cells and conversely, negative
      correlations between the perivascular CD8(+) T cells and JCV-infected glial cells
      in the surrounding brain. Most of these correlations remained significant after
      accounting for the degree of demyelination and location of the cells relative to
      lesions. Moreover, high numbers of CD8(+) T cells were found within and at the
      border of active PML lesions. These results suggest that CD8(+) T cells are
      primarily associated with JCV-infected glial cells in most PML cases and that an
      active ongoing recruitment of CD8(+) T cells and possibly viral antigen-specific
      retention could occur. These observations are discussed in the context of the
      recent evidence of PML in multiple sclerosis and Crohn's patients treated with
      natalizumab, underscoring the role of CD8(+) T lymphocytes in continued
      immunosurveillance of the CNS.

PMID- 16798674
TI  - Temporal analyses of the neuropathogenesis of a West Nile virus infection in
      mice.
AB  - A West Nile virus (WNV) infection in humans can produce neurological symptoms
      including acute flaccid paralysis, encephalitis, meningitis and myelitis. To
      investigate the pathogenesis of WNV in the peripheral and the central nervous
      system (PNS and CNS), the authors used a murine footpad inoculation model of WNV
      infection. Survival curves of virus-infected animals of ages 4- to 6-weeks-old
      demonstrated age-dependent mortality where older animals (6-weeks-old) had a
      higher mortality rate compared to younger animals (4- and 5-weeks-old). The mice
      that survived the virus infection formed WNV-reactive antibodies, confirming
      viral infection and clearance. The localization of viral RNA (vRNA) and antigen
      in infected murine tissues was investigated using TaqMan and immunohistochemistry
      (IHC) respectively. During a nine day infection, vRNA levels in the spinal cord
      and brainstem fluctuated, suggesting early viral clearance from these tissues by
      days 3-4 p.i. with later re-introduction. Viral antigens detected using IHC were
      primarily observed in three main regions of the brain: cortex, hippocampus and
      brainstem. Additionally, the dorsal root ganglion neurons of the PNS stained
      positive for viral antigens. These data are consistent with multiple routes of
      neuroinvasion following a peripheral inoculation of virus and do not preclude the
      previous observation that virus-infected peripheral neurons can introduce virus
      into the CNS by a retrograde transport mechanism.

PMID- 16798676
TI  - Use of laser capture microdissection to detect integrated HIV-1 DNA in
      macrophages and astrocytes from autopsy brain tissues.
AB  - The importance of astrocytes as a reservoir of human immunodeficiency virus type
      1 (HIV-1) in the brain remains elusive. By combining immunohistochemistry, laser
      capture microdissection, and triple-nested Alu-PCR, we demonstrate integrated HIV
      1 in astrocytes and macrophages isolated directly from autopsy brain tissues of
      HIV-1-infected subjects. The ability of HIV-1 to integrate in terminally
      differentiated astrocytes suggests a permanent reservoir of provirus in brain
      that will impact the development and likely success of strategies aimed at
      eradicating HIV-1.

PMID- 16798675
TI  - Dopaminergic marker proteins in the substantia nigra of human immunodeficiency
      virus type 1-infected brains.
AB  - With the advent of highly active antiretroviral therapy, human immunodeficiency
      virus/acquired immunodeficiency syndrome (HIV/AIDS) is becoming a more chronic,
      manageable disease; nevertheless, the prevalence of neurological complications of
      AIDS is increasing. In this study, protein levels of tyrosine hydroxylase (TH)
      and dopamine transporter (DAT) in the substantia nigra of HIV-infected brains and
      -seronegative controls were determined by immunoblotting. The immunoreactivity of
      neuronal specific enolase (NSE) was used to assess cell loss. Although there were
      no changes in levels of immunoreactive DAT or NSE proteins in HIV brains, levels
      of immunoreactive TH were significantly reduced, relative to controls. These
      results suggest that decreases in TH, the rate-limiting enzyme of dopamine
      synthesis, may be a factor in the neurological manifestations of HIV infection.

PMID- 16798678
TI  - Alcohol use and risk taking among regular ecstasy users.
AB  - We examine alcohol use in conjunction with ecstasy use and risk-taking behaviors
      among regular ecstasy users in every capital city in Australia. Data on drug use
      and risks were collected in 2004 from a national sample of 852 regular ecstasy
      users (persons who had used ecstasy at least monthly in the preceding 6 months).
      Users were grouped according to their typical alcohol use when using ecstasy: no
      use, consumption of between one and five standard drinks, and consumption of more
      than five drinks ("binge" alcohol use). The sample was young, well educated, and
      mainly working or studying. Approximately two thirds (65%) of the regular ecstasy
      users reported drinking alcohol when taking ecstasy. Of these, 69% reported
      usually consuming more than five standard drinks. Those who did not drink alcohol
      were more disadvantaged, with greater levels of unemployment, less education,
      higher rates of drug user treatment, and prison history. They were also more
      likely than those who drank alcohol when using ecstasy to be drug injectors and
      to be hepatitis C positive. Excluding alcohol, drug use patterns were similar
      between groups, although the no alcohol group used cannabis and methamphetamine
      more frequently. Binge drinkers were more likely to report having had three or
      more sexual partners in the past 6 months and were less likely to report having
      safe sex with casual partners while under the influence of drugs. Despite some
      evidence that the no alcohol group were more entrenched drug users, those who
      typically drank alcohol when taking ecstasy were as likely to report risks and
      problems associated with their drug use. It appears that regular ecstasy users
      who binge drink are placing themselves at increased sexual risk when under the
      influence of drugs. Safe sex messages should address the sexual risk associated
      with substance use and should be tailored to reducing alcohol consumption,
      particularly targeting "heavy" alcohol users. The study's limitations are noted.

PMID- 16798677
TI  - Factors predicting unmet health services needs among incarcerated substance
      users.
AB  - Negative health consequences of illicit drug use, such as cardiovascular
      complications and infectious diseases, increase the likelihood of the need for
      health care. However, evidence suggests that, with the exception of emergency
      services, drug users generally are medically underserved. Furthermore, the effect
      of illicit drug use on health care utilization is becoming an especially
      important issue for the criminal justice system, because an increasing proportion
      of inmates in correctional institutions have a history of drug use. This 1998
      1999 study of 661 incarcerated men in the Kentucky prison system focused on
      predictors of unmet physical, behavioral, and overall health care needs among
      chronic substance users. Analyses revealed that White incarcerated drug users
      were more likely to report unmet physical and overall health care needs than non
      Whites and those with high school education or above were more likely to report
      unmet physical, behavioral, and overall health care needs. In addition, more
      episodes of serious illness, more mental health problems, and poorer self-rated
      health were predictive of all three types of unmet health care needs. A longer
      career of drug use emerged as a significant predictor of unmet behavioral health
      care needs, whereas more frequent drug use in the year before incarceration
      predicted unmet physical health care needs. Further research directions and
      implications for in-prison health care planning are discussed.

PMID- 16798679
TI  - Needles in the haystacks: the social context of initiation to heroin injection in
      rural Ohio.
AB  - Although there has been much research on the social context of heroin injection,
      little has been reported outside of major urban areas. This article examines
      contextual factors associated with initiation to heroin injection in rural Ohio,
      based on semistructured qualitative interviews and focus groups involving 25
      recent heroin injectors (12 women, 13 men) recruited from three contiguous
      counties between June 2002 and February 2004. Curiosity about the drug's effects,
      the growing pressures of drug dependence and economic need, and the influence of
      intimate and group relations were all identified as factors that offset fears
      commonly associated with injection. This study complements other research on the
      social ecology of heroin injection and may contribute to improved services for
      injection drug users in rural areas and small communities.

PMID- 16798680
TI  - Predictors of engagement in vocational counseling for methadone treatment
      patients.
AB  - Employment enhances the outcomes of substance dependency treatment.
      Unfortunately, although unemployed methadone treatment patients frequently state
      they are interested in a job, many fail to participate in vocational services
      when available. Unless patients become engaged, vocational services do not have
      an opportunity to be effective. This is the first study to explore a broad array
      of factors that may be associated with differential engagement in vocational
      services among methadone patients. The study was conducted in two methadone
      programs in New York City during 2001-2004. Unemployed methadone patients (n =
      211) were voluntarily randomly assigned to either of two vocational counseling
      programs (standard vs. experimental) and followed for 6 months. The sample was
      59% male, 75% minority group, aged 45 years on average, and in methadone
      treatment for 5 years on average. Being engaged in the vocational counseling
      programs was defined as five or more sessions with the counselor in the first 6
      months after study entry. In multivariate analysis, the factors associated with
      higher engagement in vocational counseling were being non-Hispanic, having more
      education, a drug injection history, a crack use history, having chronic
      emotional/mental problems, better work attitudes, and assignment to the
      experimental vocational program. The results indicate that it is often the most
      "needy" unemployed methadone patients who become more engaged in vocational
      counseling. A vocational counseling model which emphasizes assertive outreach and
      attends to nonvocational clinical issues as well is more likely to engage
      patients.

PMID- 16798681
TI  - Illicit peyote use among American Indian adolescents in substance abuse
      treatment: a preliminary investigation.
AB  - Few studies to date have addressed illicit (i.e., nonceremonial) peyote use among
      American Indians (AIs). Participants were 89 AI adolescents admitted to a
      tribally operated residential substance abuse treatment program (RSATP) between
      1998 and 2001. The RSATP is designed to provide specialized treatment of patients
      with substance use and other comorbid psychiatric disorders and is infused with a
      culturally sensitive approach to treatment. The participants completed a series
      of interviews that collected information on psychiatric diagnostic status,
      history of substance use, and ethnic identity. The majority of participants were
      male (65%), did not come from a two-parent household (75%), reported a mean use
      of 5.4 substances, and met full criteria for a median of 2.9 substance use
      disorders. Of 89 clients, 10 (11.2%) reported illicit use of peyote. The vast
      majority of these youth (n = 8) reported using peyote only once or twice in their
      lifetime. Illicit peyote users did not differ from nonusers in terms of age,
      gender, other substance use, prevalence of either other substance
      abuse/dependence or other nonsubstance use psychiatric disorders. However,
      illicit peyote users were more likely to report low levels of social support, low
      levels of self-esteem, and low identification with AI culture yet comparable
      involvement in AI traditional practices. The results of this exploratory study
      suggest that illicit peyote use is uncommon among AI adolescents with serious
      substance abuse problems.

PMID- 16798682
TI  - Psychotropic substance abuse among adolescents: a structural equation model on
      risk and protective factors.
AB  - The use of psychotropic substances in adolescents represents a serious public
      health problem. In this study a representative sample of 485 Austrian students
      between 14 and 18 years of age were investigated with a semistructured interview
      about substance-related issues and completed the general health questionnaire.
      The following rates of regular psychotropic substance use were found: cigarettes
      41.4%, alcohol 44.5%, cannabis 10.1%, and other illicit substances 3%. Logistic
      regression analyses and structural equation modeling revealed the following major
      risk factors for substance use: peer pressure, negative family atmosphere, school
      difficulties, and psychopathology. Knowledge about substance use acted as a
      protective factor. Prevention of adolescent substance use and misuse should aim
      at these different targets. Information about coping with peer pressure may be a
      particularly promising route of intervention.

PMID- 16798683
TI  - Substance use disorders in men with antisocial personality disorder: a study in
      Turkish sample.
AB  - This study investigated the prevalence of substance use disorders (SUDs) and
      "substance of choice" in 500 male Turkish psychiatric outpatients manifesting a
      DSM-IV diagnosed antisocial personality disorder (APD) and a SUD diagnoses (the
      Structured Clinical Interview for DSM-IV). Lifetime SUDs were diagnosed in 86% of
      APD subjects. Alcohol, cannabis, and inhalant use disorders were the most
      frequent among substance use, 75.6%, 67.4%, and 35.6%, respectively. This
      sample's "substance of choice" differed from reported Western populations; a
      result which may be influenced by socio-cultural variations. The study's
      limitations are noted.

PMID- 16798684
TI  - A sober Reich? Alcohol and tobacco use in Nazi Germany.
AB  - Alcohol and tobacco use did not fit well with National Socialist aesthetics.
      However, these substances were not proscribed in Nazi Germany in spite of the
      heavy penalties for excessive use: Alcoholics were sterilized, and smoking by
      children was a criminal offense. This article argues that the great demand of the
      German people for these products prevented the authoritarian regime from alcohol
      and tobacco prohibition but measures were taken by the Nazis to reduce tobacco
      and alcohol consumption in the next generation.

PMID- 16798685
TI  - Elevated risk for tobacco use among men who have sex with men is mediated by
      demographic and psychosocial variables.
AB  - Men who have sex with men (MSM) may be more likely to smoke than general
      population men. Such population comparisons typically do not control for
      demographic differences and have not tested reasons for MSMs' greater tobacco
      use. We compared MSM with general population men in data that allowed us to
      control demographic differences, and hypothesized that MSM would report more
      tobacco use, due to elevated levels of three psychosocial variables that
      generally predict tobacco use: depression symptoms, alcohol use, and limited
      health access. Data were from a 2001 survey of MSM in Chicago (n = 817) and from
      the 2001 National Health Interview Study (n = 7,783). Significantly more MSM used
      tobacco, particularly younger MSM. Depression symptoms, alcohol use, and limited
      health access were more common among MSM and partially accounted for their
      elevated smoking risk. The lower health access and greater vulnerability of MSM
      to depression and alcohol use contributed to their higher smoking rate and must
      be considered in further smoking research and prevention. Younger MSM show very
      high rates of smoking and are a particular intervention target. Limitations of
      this cross-sectional study are noted.

PMID- 16798686
TI  - Helicobacter pylori occurrence and transmission: a family affair?
AB  - About half of the world's population is estimated to be infected with
      Helicobacter pylori, a gastric bacterium that contributes to the development of
      peptic ulcer disease and gastric cancer. H. pylori is more prevalent in low
      income areas of the world and social and economic development decreases the
      prevalence as reflected in comparisons both within and between countries. The
      infection is typically acquired in early childhood and once established commonly
      persists throughout life unless treated. Person-to-person transmission within the
      family appears to be the predominant mode of transmission, particularly from
      mothers to children and among siblings, indicating that intimate contact is
      important. The route of transmission is uncertain, but the gastro-oral, oral-oral
      and faecal-oral routes are likely possibilities. Hence, gastroenteritis may
      facilitate dissemination of the infection. The community and environment may play
      additional roles for H. pylori transmission in some (low-income) settings.
      Furthermore, host and bacterial factors may modify the probabilities of
      acquisition and persistence of the infection. The understanding of H. pylori
      occurrence and transmission is of practical importance if future study deems
      prevention of the infection desirable in some high-prevalence populations. The
      present paper reviews aspects of H. pylori occurrence and transmission with an
      emphasis on household factors.

PMID- 16798687
TI  - Analysis of genetic diversity among Staphylococcus aureus isolates from patients
      with deep-seated and superficial staphylococcal infections using pulsed-field gel
      electrophoresis.
AB  - Molecular typing was performed to reveal the genetic diversity among
      Staphylococcus aureus strains causing deep-seated versus superficial
      staphylococcal infections. Pulsed-field gel electrophoresis with cluster
      analysis, plasmid and antimicrobial susceptibility profiling of 50 S. aureus
      strains collected from these 2 groups of patients were undertaken. A total of 19
      (designated A through S) distinct genotypes were identified by PFGE of Sma I
      digested genomic DNA. The most prevalent PFGE type was L, which accounted for 30%
      of isolates and was detected among superficial isolates only. The second most
      prevalent PFGE type, type A (18%), was predominant among deep-seated isolates.
      Remaining PFGE types varied in distribution between the 2 groups. Plasmid profile
      analysis revealed that deep isolates harbour plasmids more frequently (comprising
      64% of isolates) than superficial isolates (4%) and showed 10 and 2 distinct
      patterns, respectively, with pattern 1 being the dominant among deep isolates.
      Antimicrobial susceptibility data suggested an increased prevalence of antibiotic
      resistance among deep isolates with the majority (40%) exhibiting identical
      antibiograms compared to superficial isolates. No resistance was detected against
      clindamycin and vancomycin. The results of our study indicate a previously
      unrecognized dichotomy of S. aureus strains, causing deep-seated and superficial
      infections.

PMID- 16798688
TI  - Serotypes of Streptococcus pneumoniae isolated from blood and cerebrospinal fluid
      related to vaccine serotypes and to clinical characteristics.
AB  - Pneumococci isolated from blood and cerebrospinal fluid from 1998 to 2001 in 2
      counties in south-west Sweden were serotyped with the capsular reaction test. Of
      the 836 strains, 353 (42%), 598 (72%) and 789 (94%) belonged to serotypes
      included in the 7- and 11-valent pneumococcal conjugate vaccines and in the 23
      valent polysaccharide vaccine, respectively. The most common serotype was type 1
      (119 isolates) followed in descending frequency by serotypes 7F, 9V, 14, 4 and
      12F (90-49 isolates per serotype). The coverage rates of the 7- and 11-valent
      conjugate vaccines among 58 strains isolated from children and adolescents 0-19 y
      of age were 46% and 93%, respectively. A comparison of clinical characteristics
      of infections caused by different serotypes showed that types 1 and 7F were less
      commonly associated with severe underlying diseases, that patients infected with
      these serotypes were younger than the average and, thus, had a lower case
      fatality rate.

PMID- 16798689
TI  - Osteoarticular infections complicating infective endocarditis: a study of 30
      cases between 1969 and 2002 in a tertiary referral centre.
AB  - Osteoarticular infections (osteomyelitis and septic arthritis) were studied in
      693 episodes of infective endocarditis (IE) presenting to St. Thomas' Hospital
      (STH) between 1969 and 2002. The incidence of osteoarticular infections (OAI) was
      4.3% (30/693). In intravenous drug users (IVDU), the incidence of OAI was 17.6%
      (9/51). 22 (73%) were clinically definite by the modified Duke criteria and 8
      (27%) were probable. The respective figures using the St. Thomas' modified
      criteria were 83% and 17%. Blood cultures were positive in 93% (27/29). Only Gram
      positive organisms were isolated. Infection mainly involved the vertebrae and
      large joints. Culture of joint fluid or bone was positive in 82% of cases
      (14/17). Over half the patients who developed OAI had major embolic complications
      of IE and the overall mortality was 33%. Bivariate analysis of risk factors for
      OAI in endocarditis showed statistical significance for S. aureus bacteraemia (OR
      4.2, 1.9-9.3), IVDU (OR 6.3, 2.5-15.7), tricuspid valve involvement (OR 4.2, 1.8
      9.6), pulmonary emboli (OR 3.9, 1.2-11.8) and emboli to the CNS (3.9, 1.5-9.9);
      on multivariate analysis, however, only S. aureus bacteraemia (OR 3.9, CI 2.5
      5.9) and IVDU ( OR 3.2, CI 2.0-5.2) were associated with OAI in IE.

PMID- 16798691
TI  - Gram-negative bacteria from patients seeking medical advice in Stockholm after
      the tsunami catastrophe.
AB  - Microbiological cultures from 229 patients seeking medical advice in Stockholm
      after the tsunami catastrophe of December 2004 were analysed at the Clinical
      Microbiology Laboratory, Karolinska University Hospital, Stockholm, Sweden. Gram
      negative bacilli were the most common findings from wound cultures. Common human
      pathogens such as Escherichia coli, Proteus species, Klebsiella spp., and
      Pseudomonas aeruginosa were isolated. More rare species of Gram-negative bacilli,
      e.g. Myroides odoratus, Sphingomonas paucimobilis and Bergeyella zoohelcum were
      also isolated. Resistance towards ordinary antibiotics was more extensive
      compared to our Swedish reference material for Escherichia coli, Klebsiella
      pneumoniae, Proteus mirabilis and Acinetobacter spp., but not for Pseudomonas
      aeruginosa, probably reflecting that the resistant isolates were nosocomially
      acquired in Asia.

PMID- 16798690
TI  - ICU stay promotes enrichment and dissemination of multiresistant coagulase
      negative staphylococcal strains.
AB  - Patients in the intensive care unit (ICU) are prone to be colonized and infected
      by multi-resistant bacteria. It is previously known that nosocomial infections
      are often preceded by cross-transmission events. The aim of the present
      investigation was to study the impact of the patient's length of ICU stay on the
      resistance patterns, diversity and dissemination of coagulase-negative
      staphylococci (CoNS) within and between patients. Two groups of patients were
      studied, including 20 consecutive patients sampled within 2 h from admission
      (short-stayers, SS), and all patients treated for at least 5 d in the ICU (long
      stayers, LS), available for sampling every second week (n = 15). Sampling was
      performed from 5 sites: oropharynx, nares, neck, axilla and perineum. A total of
      868 CoNS isolates deriving from LS patients and 403 isolates from SS patients
      were analysed for antimicrobial susceptibility, clonal diversity and
      dissemination within and between patients. The highest resistance rates were seen
      for oxacillin and ciprofloxacin, being 92% and 83%, respectively. Long-stayers
      were at significantly higher risk of being colonized with CoNS isolates resistant
      against oxacillin, clindamycin, ciprofloxacin, gentamicin as well as with
      multiresistant strains. By genotyping 22 phenotypes that were shared among at
      least 2 patients, 32 PFGE types of which 16 colonized more than 1 individual were
      identified. One of the clones was isolated from 10 individuals, including 2 SS
      patients, indicating an epidemic strain. Prolonged ICU stay was significantly
      correlated to decreased clonal diversity, increased endogenous dissemination of
      resistant strains and cross-transmission. The results emphasize the importance of
      good infection control practice, especially in this vulnerable group of patients.

PMID- 16798692
TI  - Murine typhus is a common cause of febrile illness in Bedouin children in Israel.
AB  - Murine typhus is known to be endemic among populations living in poverty and
      exposed to rats and their fleas. A prospective 2-y study was conducted to
      determine the contribution of murine typhus to undifferentiated febrile illnesses
      among Bedouin children attending an outpatient clinic in southern Israel.
      Children with fever > or = 38.5 degrees C lasting for > or = 3 d were enrolled in
      the study. Murine typhus was serologically confirmed by the
      microimmunofluorescence test. A total of 549 children met the inclusion criteria
      of whom 76 (13.8%) had serologically-confirmed murine typhus. The disease was
      diagnosed in 27 of 434 (6.2%) patients aged < 5 y and in 49 of 115 (42.6%) older
      children (p<0.001). Murine typhus was diagnosed in 54 of 288 (18.8%) patients
      between June and November and in 22 of 261 (8.4%) between December and May
      (p<0.001). Patients with murine typhus had significantly higher prevalence of
      anaemia, leukopenia, hyponatraemia, and elevated liver enzymes compared to
      children without the disease. A single child was hospitalized and all 76 patients
      recovered without complications. Murine typhus is an important cause of febrile
      illnesses among Bedouin children > or = 5 y of age living in southern Israel and
      usually runs a benign clinical course.

PMID- 16798693
TI  - Prevalence and mechanisms of macrolide resistance in Streptococcus pyogenes in
      Ankara, Turkey.
AB  - From 2002 to 2003, a total of 381 consecutive S. pyogenes isolates were obtained
      from throat swabs (n = 337) and samples of pus (n = 31), sputum (n=10) and blood
      (n = 3) at Hacettepe University Hospital. The susceptibility of the isolates to
      erythromycin was tested by the agar dilution method. Erythromycin resistant
      strains were then tested for their MICs to azithromycin, clindamycin, and
      penicillin, their phenotype of resistance to macrolides-lincosamides
      streptogramin B (MLSB) and for the presence of macrolide resistance genes. The
      rate of resistance to erythromycin was 6.8%. Constitutive (cMLSB), inducible
      (iMLSB), and M phenotypes of resistance were detected in 7.7, 30.8, and 57.7% of
      resistant strains, respectively. One strain had both cMLSB and iMLSB phenotypes.
      All M phenotypes carried the mefA gene, all iMLSB phenotype carried the ermTR
      gene, 1 isolate with cMLSB phenotype harboured the ermB gene, and 1 isolate with
      cMLSB phenotype carried both the ermB and mefA genes. One strain which showed
      cMLSB and iMLSB phenotypes harboured the ermB gene.

PMID- 16798694
TI  - Intestinal parasites in adults admitted to a rural Ethiopian hospital:
      Relationship to tuberculosis and malaria.

PMID- 16798695
TI  - The most prevalent Mycobacterium tuberculosis superfamilies among Iranian and
      Afghan TB cases.
AB  - This survey identified the spoligopatterns of Mycobacterium tuberculosis strains
      with an international designation responsible for transmission and prevalence of
      TB (2000 to 2005) among native and immigrant populations of Tehran. The spacer
      oligonucleotides typing was performed on 1742 Mycobacterium tuberculosis strains
      isolated from verified cases of TB. Clinical and demographic data of patients
      were collected using traditional methods. A total of 133 distinct spoligopatterns
      was observed. 1679 clinical isolates were clustered in 70 clusters (52.5%) and 63
      isolates were defined as orphans pattern (47.3%). Based on an international
      spoligotype database, the east African-Indian (EAI, 24%), central Asian (CAS,
      20.8%), T clade (20.7%), Haarlem I (4.4%), Beijing (3.2%) and shared type 253
      (3.1%) were the major identified M. tuberculosis superfamilies. Our results
      showed that the intra-community TB transmission was 13.7%, whereas the inter
      community transmission was 39.3% for Afghanis and 20.3% for Iranians. The study
      highlighted the epidemic potential of specific genotypes (EAI, CAS, T clades)
      among tuberculosis cases in the Tehran territory. We also confirmed that the
      impact of transmission through immigration is low.

PMID- 16798696
TI  - Multiple, severe lung infiltrates due to Mycobacterium avium-intracellulare in a
      patient with decompensated liver cirrhosis: Spontaneous resolution after a two
      year follow-up.
AB  - A unique case of severe, multiple, microbiologically-confirmed pulmonary
      Mycobacterium avium-intracellulare lesions occurred in a female with
      decompensated liver cirrhosis, and went to cure after around 2 y despite the
      impossibility to deliver an effective antimicrobial chemotherapy, owing to the
      patient's intolerance. From an extensive literature review, we underline a
      possible mechanism prompting mycobacterial disease during advanced liver disease,
      while we retrieved only 2 described cases of possible spontaneous resolution of
      Mycobacterium terrae lung disease, although both were reported in patients
      without end-organ liver disease, who received a specific combined chemotherapy
      for an appreciable time period. On the other hand, while decompensated liver
      cirrhosis is more frequently complicated by a peritoneal localization of bacteria
      and very infrequently mycobacteria, the reported case represents the first severe
      pulmonary localization of multiple lesions due to Mycobacterium avium
      intracellulare. Moreover, this extraordinary episode resolved spontaneously
      within the 2-y follow-up, as documented by bronchoalveolar lavage, culture, high
      resolution CT scans, and scintigraphic examination.

PMID- 16798697
TI  - A survey of anti-malarial activity during pregnancy, and children's malaria care
      seeking behaviour in two Nigerian rural communities.
AB  - This study investigated anti-malarial prophylaxis during pregnancy and children's
      malaria care-seeking behaviour by mothers with children 5 y of age and below
      drawn from 2 rural communities in southern Nigeria. Findings showed that 37% of
      mothers said they had used anti-malarial prophylaxis (chloroquine, 50%) during
      pregnancy, while only 30% of them had bed net (untreated) at home, with 44% of
      the bed net damaged. Over half (59%) of the respondents reported that their
      children had had fever/malaria in the forthnight recall period, and a majority of
      them (44%) were treated in medicine shops. Injections accounted for 33% of the
      medications received by them. Of the 74% of children who were given treatment,
      there were delays of 2 or more d in seeking care for a quarter of them. Only 21%
      of the mothers attributed malaria to bites from infected mosquitoes, despite the
      high prevalence of childhood malaria. Low coverage of anti-malarial intervention
      during pregnancy and inappropriate children's malaria care-seeking behaviour has
      been identified. An appropriate mechanism for delivery of insecticide-treated bed
      nets in addition to educational interventions is recommended in order to reduce
      the burden of malaria among pregnant women and children in these communities.

PMID- 16798698
TI  - Saccharomyces boulardii and infection due to Giardia lamblia.
AB  - Therapy with metronidazole is the recommended option in giardiasis. However, some
      clinical trial reports suggest the appearance of drug resistance to explain
      therapeutic failure. Several investigations have been carried out on the effect
      of probiotic microorganisms for preventing or treating gastrointestinal diseases,
      but little is known about their efficacy against protozoal infections. The
      principal objective of our study was to evaluate the efficacy of Saccharomyces
      boulardii against Giardia lamblia infections. A double-blind, placebo-controlled
      study was carried out on adult patients with giardiasis. Group 1 (30 patients)
      included metronidazole 750 mg 3 times daily along with S. boulardii capsules (250
      mg b.i.d. orally) for 10 d while group 2 (35 patients) was treated with
      metronidazole 750 mg 3 times daily and with empty capsules as placebo for 10 d.
      Patients were re-examined at 2 and 4 weeks after treatment, and stool
      examinations were performed. At week 2, G. lamblia cysts were detected in 6 cases
      (17.1%) of group 2 and none in group 1. At the end of the fourth week, presence
      of the cysts continued in the same 6 cases in group 2 (control group). These
      findings indicated that S. boulardii may be effective in treating giardiasis when
      combined with metronidazole therapy.

PMID- 16798699
TI  - Enhanced surveillance of newly acquired hepatitis C virus infection in Canada,
      1998 to 2004.
AB  - The purpose of this study was to determine trends in disease incidence and recent
      patterns of hepatitis C virus (HCV) transmission in Canada, using the Enhanced
      Hepatitis Strain Surveillance System (EHSSS). Demographic, clinical, and
      potential risk factor information on newly acquired HCV infection, from 1998 to
      2004, was collected using standardized questionnaires. During this time period,
      the reported incidence of newly acquired HCV infection declined by 36.4% from 3.3
      cases per 100,000 in 1998, to 2.1 cases per 100,000 in 2004. The disease
      incidence peaked at 15 to 39 y of age, confirming injecting drug use as the most
      frequently reported route of transmission. The proportion of cases attributed to
      health care-acquired HCV infection decreased over this time period. Although the
      incidence of newly acquired HCV infection in the EHSSS was found to be declining,
      hepatitis C remains an important public health threat to Canadians. Prevention
      efforts for HCV should focus on injection drug use, especially for people aged 15
      to 39 y.

PMID- 16798700
TI  - An outbreak of rotavirus infection among adults in an institution for
      rehabilitation: long-term residence in a closed community as a risk factor for
      rotavirus illness.
AB  - An outbreak of group A rotavirus infection resulted in gastroenteritis among
      disabled adults in an isolated rehabilitation institution in Kobe, Japan. Of the
      95 residents, 16 were diagnosed with rotavirus illness. The causative agent was a
      single strain of typical human group A rotavirus belonging to VP7 serotype G2,
      VP4 genotype P[4], and NSP4 genotype A. Mean duration of stay was significantly
      longer for residents with rotavirus illness (22.1+/-11.8 years) than for
      residents without the disease (13.5+/-10.6 years; P=0.01). Age, sex, disability
      and location of resident rooms displayed no significant relationships with
      illness. These observations suggest that long-term residence in a closed
      community, which might be related to absence of immuno-stimulation, represents a
      risk factor for rotavirus illness.

PMID- 16798702
TI  - Comparison of two vaccination programmes in preventing influenza-related
      hospitalization among the elderly during two consecutive seasons.
AB  - The protective effect of influenza vaccine against influenza related
      hospitalization is well established at an individual level, but the effect of
      vaccination programme at the population level is unknown. In this study we
      compared a risk disease-based free-of-charge influenza vaccination programme in
      preventing hospitalizations due to influenza or pneumonia and cardiovascular
      diseases during 2 consecutive influenza seasons 1992/93 and 1993/94 in 43
      municipalities in northern Finland. Vaccinations were carried out and reported by
      local staff in health centres. Data of hospital treatment periods were obtained
      from the National Hospital Discharge Register. During the influenza seasons the
      number of hospitalizations due to cardiovascular diseases and influenza/pneumonia
      increased by 13%. In the 1993/1994 season the increase in the study area with the
      risk disease-based vaccination programme was 22 per 1000 persons (95% CI 19-24),
      and with an age-based programme 3.3 per 1000 persons (95% CI 2.5-4.0), while the
      increase in the 1992/1993 season in both areas was 3-4 per 1000. The excess of
      hospitalization related to influenza epidemics is mostly due to cardiovascular
      diseases and varies from y to y, as do the benefits gained by vaccination.

PMID- 16798701
TI  - Cost-effectiveness of peginterferon alfa-2b in combination with ribavirin as
      initial treatment for chronic hepatitis C in Sweden.
AB  - The aim of the study was to assess the cost-effectiveness of peginterferon alfa
      2b (pegIFN) compared to interferon alfa-2b (IFN), both in combination with
      ribavirin, as initial therapy for chronic hepatitis C in Sweden. A computer based
      Markov model describing the natural course of chronic hepatitis C was used to
      assess costs and quality-adjusted life-y (QALY) for the treatment strategies.
      Study population was a cohort of hepatitis C patients from the age of 43 y until
      death. Natural history and response data were obtained from the literature and
      from Swedish clinical experts. Costs were obtained from different health care
      providers in Sweden and based on Swedish clinical practice. In our base case
      analysis for genotype 1 patients, pegIFN plus ribavirin therapy generated 0.29
      incremental QALYs and was cost saving (dominant strategy). Corresponding results
      for genotype 2/3 patients were 0.09 QALYs at an incremental cost of 941 euros
      (10,500 euros/QALY). A probabilistic sensitivity analysis was performed to study
      the stability of our results. From the results we conclude that for genotype 1
      patients treatment with pegIFN and ribavirin increased quality-adjusted life
      expectancy and was cost-effective as initial therapy for hepatitis C. The cost
      effectiveness for patients infected with genotype 2/3 was less obvious.

PMID- 16798703
TI  - Genetic analysis of Puumala hantavirus strains from Austria.
AB  - Sequences of the Small (S) and the Medium (M) genome segments of Puumala
      hantavirus (PUUV) were recovered from bank voles Clethrionomys glareolus trapped
      at 2 locations, Klippitztorl (Carinthia) and Ernstbrunn (Lower Austria). Lung
      tissue samples from 12 rodents earlier found hantavirus antibody-positive were
      further screened for the presence of hantaviral N-antigen using immunoblotting.
      RNA purified from 7 N-Ag-positive samples was subjected to the reverse
      transcription-polymerase chain reaction with primers designed to recover the
      complete S segment sequence of PUUV. The amplicons of expected size
      (approximately 1800 bp) have been recovered from 2 samples, 1 from Klippitztorl
      and another from Ernstbrunn. From the same 2 samples, PCR amplicons corresponding
      to the partial M segment sequence (nt 2140 to 2594), have been prepared. The S
      and M amplicons were sequenced and subjected to genetic analyses. Recovered
      hantavirus genome sequences undoubtedly belonged to PUUV genotype and the
      corresponding wild-type hantavirus strains were designated as
      PUU/Klippitztorl/Cg9/1995 and PUU/Ernstbrunn/Cg641/1995. Phylogenetic analysis
      placed 2 Austrian PUUV strains within a distinct genetic lineage that also
      included strains from the neighbouring Slovenia and Croatia. This Alpe-Adrian
      lineage, previously designated as 'Balkan lineage', was well supported on both S
      and M phylogenetic trees.

PMID- 16798704
TI  - Tick-borne encephalitis in eastern France.
AB  - Each y a few cases of TBE infection are described in Alsace, France which lies at
      the occidental limit of the endemic zone of tick-borne encephalitis (TBE). Hence
      we carried out a retrospective epidemiological and clinical study of TBE
      infection in Alsace. Data were collected from serological results sent to the
      Institut de Virologie (Universite Louis Pasteur) in Strasbourg. All samples
      positive for specific IgM against TBE were retained. The physician in charge of
      each patient was asked to provide clinical, epidemiological and biological data
      and with his agreement the medical file was referred to us. Since 1968, 64 cases
      of TBE infection, occurring between April and November, had been described. In
      56% of cases, flu-like symptoms preceded neurological symptoms. Most patients had
      meningitis (54%) or meningoencephalitis (34%). There was no death due to TBE. Two
      areas were more highly endemic for the disease: the Guebwiller valley in low
      mountain country and the Neuhof forest, near Strasbourg in the plain of Alsace.
      In the last 2 y of the study, a third zone seemed to emerge, in the Munster
      valley. This epidemiological survey revealed the existence in Alsace of 2 endemic
      zones of TBE with a third zone possibly emerging in the last few y. The survey
      must be continued to follow the evolution of the disease.

PMID- 16798705
TI  - Which patient is a candidate for empirical therapy against Stenotrophomonas
      maltophilia bacteraemia? An analysis of associated risk factors in a tertiary
      care hospital.
AB  - Stenotrophomonas maltophilia is an emerging nosocomial pathogen with a tendency
      to be resistant to several antibiotics commonly used to treat nosocomial
      infections. Early recognition of the risk factors for bacteraemia caused by S.
      maltophilia could potentially improve the prognosis in these cases. Most data
      have been obtained from a limited number of descriptive studies. In this
      retrospective case-control study, we investigated the risk factors for S.
      maltophilia bacteraemia. We compared cases with 2 different control groups; non
      bacteraemic patients and those with bacteraemia caused by Escherichia coli. 37
      cases were matched with 37 control patients with nosocomial E. coli bacteraemia
      and 74 non-bacteraemic patients. The demographic information was extracted from
      the chart of the patients. When the effects of multiple factors were analysed
      simultaneously, the presence of a central venous catheter and carbapenem use were
      associated with an increased risk for bacteraemia caused by S. maltophilia
      compared with both the non-bacteraemic and bacteraemic control groups. We found a
      mortality rate of 21.6% in cases vs non-bacteraemic controls; however, this was
      not a statistically significant difference from that observed in patients with E.
      coli bacteraemia.

PMID- 16798706
TI  - Coccidioidomycosis with cerebral and cerebellar granulomas.
AB  - We discuss the diagnosis, treatment and prognosis of a Danish male with
      disseminated coccidioidomycosis. He presented with headaches and slight fever.
      Examination showed pulmonary, cutaneous and cerebral and cerebellar granulomas, a
      rare complication. He was treated with intravenously and subsequently orally
      administered fluconazole. Symptoms and clinical findings regressed during
      treatment.

PMID- 16798707
TI  - Successful treatment of Pasteurella multocida meningitis with aztreonam.
AB  - This is the first reported case of the successful treatment of Pasteurella
      multocida meningitis with aztreonam in a patient with multiple antibiotic
      allergies.

PMID- 16798709
TI  - Asymptomatic Mycobacterium xenopi lung abscess in an immunocompetent male without
      pre-existing lung pathology.
AB  - Like other non-tuberculous mycobacteria, Mycobacterium xenopi infects more
      commonly patients with altered immune defenses. In immunocompetent individuals,
      infection with M. xenopi has been described in the setting of underlying lung
      disease. We here report the first case of M. xenopi lung abscess in a previously
      healthy patient with no known predisposing factors who was successfully treated
      with rifampin, isoniazid and ethambutol.

PMID- 16798708
TI  - UGT1A1 promoter polymorphism as a predisposing factor of hyperbilirubinaemia in
      neonates with acute pyelonephritis.
AB  - We describe 4 jaundiced neonates with acute pyelonephritis of whom family history
      was positive for or pointed to Gilbert's syndrome (GS). Uridine diphosphate
      glucuronosyltransferase 1A1 (UGT-1A1), (TA)7 polymorphism, associated with GS was
      found in these neonates. We suggest that extended (TA)7 promoter, acting as a
      predisposing factor, contributes substantially to hyperbilirubinaemia seen in a
      number of neonates with urinary tract infections (UTIs).

PMID- 16798710
TI  - Disseminated nocardiosis due to unusual species: two case reports.
AB  - Pulmonary nocardiosis is the major clinical manifestation of human nocardiosis
      and disseminated infection can be seen in immunocompromised patients. N.
      asteroides is the predominant pathogen associated with disseminated diseases. We
      report 2 cases of pulmonary nocardiosis admitted with disseminated infection,
      caused by rare species of Nocardia: Nocardia transvalensis and Nocardia
      cyriacigeorgica.

PMID- 16798711
TI  - Myopericarditis in a patient with Campylobacter enteritis: a case report and
      literature review.
AB  - Myocarditis sometimes occurs as a complication of bacterial infection, including
      enteric infections caused by Salmonella, Shigella and Yersinia. Only a few cases
      of Campylobacter-associated myocarditis are known. We describe a 47-y-old patient
      with myopericarditis in association with Campylobacter spp. enteritis, and review
      similar cases previously described in the English literature.

PMID- 16798712
TI  - Lung mass caused by Phoma exigua.
AB  - We describe a well documented case of a fatal Phoma exigua lung infection in a
      patient with acute myeloid leukaemia and diabetes. The infection was histology
      and culture proven and a PCR assay was developed for detecting P. exigua DNA in
      deparaffinized lung-biopsy material. Confirmation of rare fungal pathogen
      infections requires a multidisciplinary approach involving clinical observations,
      mycology, histopathology and radiology.

PMID- 16798713
TI  - Psoriasiform lupus vulgaris with 30 years duration.
AB  - Lupus vulgaris is a progressive form of cutaneous tuberculosis occurring in a
      person with a moderate to high degree of immunity. It is the most common type of
      cutaneous tuberculosis. Lupus vulgaris can be mimicked by several other skin
      conditions, and a 69-y-old female is described with an extremely long history of
      extensive infiltrative skin lesions with abundant scaling. The lesions were
      localized on the right arm and forearm, and on the right lateral surface of the
      chest. The diascopic test was positive. Moreover, a large atrophic scar was seen
      in the region of right cubital fossa resulting in contracture of the right elbow
      joint. The histopathology strongly suggested the diagnosis of tuberculosis. The
      final diagnosis of tuberculosis was confirmed by PCR examination. A
      polychemotherapeutic regimen (ethambutol 1250 mg/d, rifampicin 600 mg/d and
      isoniazid 300 mg/d) was successfully employed for the treatment of skin lesions.

PMID- 16798714
TI  - Caspofungin treatment in two infants with persistent fungaemia due to Candida
      lipolytica.
AB  - Candida lipolytica has infrequently been identified as a cause of infection and
      is associated mostly with vascular catheter-related fungaemia. Patients reported
      in the literature have been successfully treated with catheter removal or
      amphotericin B treatment. We report 2 infants with C. lipolytica fungaemia
      unresponsive to catheter removal and amphotericin B therapy and treated
      successfully with the addition of caspofungin to amphotericin B.

PMID- 16798715
TI  - Isolated intramedullary cryptococcal granuloma of the conus medullaris: case
      report and review of the literature.
AB  - Infection of the nervous system by Cryptococcus neoformans most often causes
      meningitis and meningoencephalitis. While there have been several cases of
      cerebral cryptoccal granuloma published in the literature, the isolated
      occurrence of intramedullary cryptococcal granuloma is very rare. We present an
      immunocompetent patient with such a lesion of the conus medullaris. The patient's
      clinical symptoms mimicked an intramedullary spinal cord tumor. The diagnosis was
      made by histopathology, rather than by image or laboratory examinations. The case
      was successfully managed with surgical removal of the lesion and postoperative
      anti-fungal treatment.

PMID- 16798716
TI  - Bladder carcinoma and HIV infection during the highly active antiretroviral
      therapy era: A rare, but intriguing association. Two case reports and literature
      review.
AB  - Two very rare case reports of bladder transitional cell carcinoma associated with
      HIV infection in patients treated with combined antiretroviral therapy are
      described, and discussed on the ground of the most relevant and updated
      literature resources. Only 13 cases of vesical carcinoma have been reported to
      date in the setting of HIV infection, but only 3 anecdotal single reports (the
      last in the y 2001) described clinical, therapeutic, and outcome issues of this
      rare disease association in some detail. In our patients, micro- or macro
      haematuria was the clue for in-depth diagnosis and prompt treatment, which was
      limited to multiple local interventions in 1 case, but finally required a radical
      cystectomy in the second patient. No relationship was found with the very
      favourable underlying HIV-related virological and immunological status, and the
      present 8-12-month follow-up did not show disease relapses.

PMID- 16798717
TI  - Recurrent HSV-2 meningitis in a 9-year-old girl.
AB  - While HSV-2 meningitis has been described in prepubertal children in the context
      of sexual abuse, to the best of our knowledge recurrent episodes have not been
      described in this population. We report a 9-y-old girl with recurrent HSV-2
      meningitis presenting as aseptic meningitis without any evidence of genital
      herpes. A high index of suspicion for this condition would be needed to make a
      diagnosis in this age group, which in turn would guide further therapeutic
      decisions.

PMID- 16798718
TI  - Prolonged latent schistosomiasis diagnosed 38 years after infestation in a HIV
      patient.
AB  - We report a case of Schistosoma mansoni bilharziasis in a HIV patient 38 y after
      leaving an endemic region. A viable S. mansoni egg on a liver biopsy sample was
      diagnostic. Despite severe concomitant immunodeficiency the effective treatment
      was a single dose of praziquantel. Worms' intravascular longevity and the role of
      immunodeficiency as a possible factor in eggs retention after such prolonged
      latent schistosomiasis are discussed.

PMID- 16798719
TI  - Proteus mirabilis spondylodiscitis complicating a urinary tract infection.
AB  - Infectious spondylodiscitis results from local or haematogenous infection by
      microorganisms of intervertebral disc spaces, vertebral bodies and surrounding
      structures. Haematogenous invasion may follow urosepsis. We report on a case of
      septic spondylodiscitis following urosepsis with Proteus mirabilis, a frequently
      isolated microorganism in urinary tract infections but rarely in
      spondylodiscitis.

PMID- 16798721
TI  - TNF-alpha is crucial for the development of mast cell-dependent colitis in mice.
AB  - Inflammatory bowel disease (IBD) describes chronic inflammatory conditions of the
      gastrointestinal tract, and TNF-alpha plays a pivotal role in mediating the
      response. The proinflammatory cytokine TNF-alpha is rapidly released by mast
      cells after degranulation. In the present study, we hypothesized TNF-alpha to be
      an important player in our recently described mast cell-dependent murine model
      for IBD. The effect of neutralizing anti-TNF-alpha MAb was studied on colonic
      hypersensitivity in mice induced by a skin application of dinitrofluorobenzene
      (DNFB) followed by an intrarectal challenge with dinitrobenzene sulfonic acid.
      Features of the colonic hypersensitivity response included diarrhea, mast cell
      infiltration and activation, infiltration of inflammatory cells in the colon,
      colonic patch hypertrophy, and increased mast cell-derived TNF-alpha levels in
      the colon. Anti-TNF-alpha MAb could effectively abrogate diarrhea in DNFB
      sensitized mice 72 h after the challenge. The numbers of colonic patches and
      total tissue damage scores were reduced by anti-TNF-alpha MAb treatment in DNFB
      sensitized mice 72 h after the challenge. Mast cell infiltration and activation
      remained unaffected by neutralizing anti-TNF-alpha MAb. Treatment with the
      corticosteroid dexamethasone, a frequently used therapeutic treatment in IBD,
      resulted in a reduction of diarrhea, cellular infiltration, and total tissue
      damage scores to the same extent as anti-TNF-alpha MAb. Additionally,
      dexamethasone treatment could also reduce total TNF-alpha levels in the colon,
      mast cell numbers, and mast cell activation in both vehicle- and DNFB-sensitized
      mice 72 h after the challenge. These findings suggest that TNF-alpha can play an
      instrumental role in causing inflammatory responses in the present murine model
      for IBD downstream from mast cell activation.

PMID- 16798720
TI  - PI3-kinase activity modulates apo B available for hepatic VLDL production in
      apobec-1-/- mice.
AB  - Insulin regulates hepatic VLDL production by activation of phosphatidylinositide
      3-kinase (PI3-kinase) which decreases apo B available for lipid assembly. The
      current study evaluated the dependence of the VLDL apolipoprotein B (apo B)
      pathway on PI3-kinase activity in vivo. VLDL production was examined in B100
      only, apo B mRNA editing catalytic subunit 1 (apobec-1(-/-)) mice, using the
      Triton WR 1339 method. Glucose injection suppressed VLDL triglyceride production
      by 28% in male and by 32% in female mice compared with saline-injected controls.
      When wortmannin was injected to inhibit PI3-kinase, VLDL triglyceride production
      was increased by 52% in males and by 89% in females, and VLDL B100 levels
      paralleled triglyceride changes. Pulse-chase experiments in primary mouse
      hepatocytes showed that wortmannin increased net freshly synthesized B100
      availability by >35%. To test whether physiological insulin resistance produced
      equivalent effects to wortmannin, we studied male apobec-1(-/-) mice who became
      hyperlipidemic on being fed a fructose-enriched diet. Fructose-fed apobec-1(-/-)
      mice had significantly higher VLDL triglyceride and B100 production rates
      compared with chow-fed mice, and rates were refractile to glucose or wortmannin.
      Hepatic VLDL triglyceride and B100 production in wortmannin-injected chow-fed
      mice equaled that observed in fructose-fed mice. Together, results suggest in
      vivo and in vitro that wortmannin-sensitive PI3-kinases maintain a basal level of
      VLDL suppression that is sensitive to changes in activation and that can increase
      VLDL production when PI3-kinase is inhibited to levels similar to those induced
      by insulin resistance.

PMID- 16798722
TI  - The emerging role of PDZ adapter proteins for regulation of intestinal ion
      transport.
AB  - In the gastrointestinal tract, CFTR, in conjunction with one or several members
      of the SLC26 anion exchanger family, mediates electrogenic Cl- and HCO3-
      secretion. Na+/H+ exchanger isoform NHE3, on the other hand, coupled to one or
      several of the SLC26 isoforms, mediates electroneutral NaCl absorption. The
      agonist-induced activation of anion secretion and inhibition of salt absorption
      causes secretory diarrhea. Current dogma sees the formation of a multiprotein
      complex of transport proteins, postsynaptic density-95/discs large/zonula
      occludens-1 (PDZ) adapter proteins, anchoring proteins, the cytoskeleton, and the
      involved protein kinases as one crucial step in the regulation of these transport
      processes. Data obtained in heterologous expression studies suggest an important
      role of these PDZ adapter proteins in trafficking, endocytic recycling, and
      membrane retention of the respective transmembrane proteins. This article reviews
      recent advances in our understanding of the role of the PDZ adapter proteins
      NHERF, E3KARP, PDZK1, IKEPP (NHERF-1 to NHERF-4), CAL, and Shank-2 that bind to
      CFTR, NHE3, and the intestinal SLC26 members in the regulation of intestinal
      fluid transport. Current concepts are mostly derived from heterologous expression
      studies and studies on their role in organ physiology are still in infancy.
      Recently, however, PDZ adapter protein-deficient mice and organ-specific cell
      lines have become available, and the first results suggest a more cell-type and
      possibly signal-specific role of these adapter proteins. This opens the potential
      for drug development targeted to PDZ domain interactions, which is, in theory,
      one of the most efficient antidiarrheal strategies.

PMID- 16798723
TI  - Proteasome inhibition attenuates hepatic injury in the bile duct-ligated mouse.
AB  - Proteasome inhibition has recently been demonstrated to inhibit hepatic
      fibrogenesis in the bile duct-ligated (BDL) mouse by blocking stellate cell NF
      kappaB activation. The effect of proteasome inhibition on liver injury, however,
      is unclear. Our aims were to assess the effect of the proteasome inhibitor
      bortezomib on liver injury in the BDL mouse. Liver injury was assessed in 7-day
      BDL mice treated with a single dose of bortezomib on day 4 after bile duct
      ligation. Despite NF-kappaB inhibition by bortezomib, liver injury and hepatocyte
      apoptosis were reduced in treated BDL mice. The antiapoptotic effect of
      bortezomib was likely mediated by an increase in hepatic cellular FLICE
      inhibitory protein (c-FLIP) levels, a potent antiapoptotic protein. Unexpectedly,
      numerous mitotic hepatocytes were observed in the bortezomib-treated BDL mice
      liver specimens. Consistent with this observation, PCNA immunoreactivity and
      cyclin A protein expression were also increased with bortezomib treatment.
      Bortezomib therapy was also associated with a decrease in numbers and activation
      of Kupffer cells/macrophages. In conclusion, these data suggest that the
      proteasome inhibitor bortezomib reduces hepatocyte injury in the BDL mouse by
      mechanisms associated with a reduction in hepatocyte apoptosis, a decrease in
      Kupffer cell/macrophage number and activation, and increased hepatocyte
      proliferation.

PMID- 16798724
TI  - Regulation of peroxisome proliferator-activated receptor-gamma in liver fibrosis.
AB  - The peroxisome proliferator-activated receptors (PPARs) impart diverse cellular
      effects in biological systems. Because stellate cell activation during liver
      injury is associated with declining PPARgamma expression, we hypothesized that
      its expression is critical in stellate cell-mediated fibrogenesis. We therefore
      modulated its expression during liver injury in vivo. PPARgamma was depleted in
      rat livers by using an adenovirus-Cre recombinase system. PPARgamma was
      overexpressed by using an additional adenoviral vector (AdPPARgamma). Bile duct
      ligation was utilized to induce stellate cell activation and liver fibrosis in
      vivo; phenotypic effects (collagen I, smooth muscle alpha-actin, hydroxyproline
      content, etc.) were measured. PPARgamma mRNA levels decreased fivefold and
      PPARgamma protein was undetectable in stellate cells after culture-induced
      activation. During activation in vivo, collagen accumulation, assessed
      histomorphometrically and by hydroxyproline content, was significantly increased
      after PPARgamma depletion compared with controls (1.28 +/- 0.14 vs. 1.89 +/- 0.21
      mg/g liver tissue, P < 0.03). In isolated stellate cells, AdPPARgamma
      overexpression resulted in significantly increased adiponectin mRNA expression
      and decreased collagen I and smooth muscle alpha-actin mRNA expression compared
      with controls. During in vivo fibrogenesis, rat livers exposed to AdPPARgamma had
      significantly less fibrosis than controls. Collagen I and smooth muscle alpha
      actin mRNA expression were significantly reduced in AdPPARgamma-infected rats
      compared with controls (P < 0.05, n = 10). PPARgamma-deficient mice exhibited
      enhanced fibrogenesis after liver injury, whereas PPARgamma receptor
      overexpression in vivo attenuated stellate cell activation and fibrosis. The data
      highlight a critical role for PPARgamma during in vivo fibrogenesis and emphasize
      the importance of the PPARgamma pathway in stellate cells during liver injury.

PMID- 16798725
TI  - Characteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated
      rat gastric glands.
AB  - The gastric H+,K+-ATPase of the parietal cell is responsible for acid secretion
      in the stomach and is the main target in the pharmacological treatment of acid
      related diseases. Omeprazole and other benzimidazole drugs, although having
      delayed efficacy if taken orally, have high success rates in the treatment of
      peptic ulcer disease. Potassium competitive acid blockers (P-CAB) compete with K+
      for binding to the H+,K+-ATPase and thereby they inhibit acid secretion. In this
      study, the in vitro properties of AZD0865, a reversible H+,K+-ATPase inhibitor of
      gastric acid secretion, are described. We used a digital-imaging system and the
      pH sensitive dye BCECF to observe proton efflux from hand-dissected rat gastric
      glands. Glands were stimulated with histamine (100 microM) and exposed to a
      bicarbonate- and Na+-free perfusate to induce an acid load. H+,K+-ATPase
      inhibition was determined by calculating pHi recovery (dpH/dT) in the presence of
      omeprazole (10-200 microM) or AZD0865 (0.01-100 microM). The efficacies of both
      drugs were compared. Our data show that acid secretion is inhibited by both the
      proton pump inhibitor omeprazole and the P-CAB AZD0865. Complete inhibition of
      acid secretion by AZD0865 had a rapid onset of activation, was reversible, and
      occurred at a 100-fold lower dose than omeprazole (1 microM AZD0865 vs. 100
      microM omeprazole). This study demonstrates that AZD0865 is a potent, fast-acting
      inhibitor of gastric acid secretion, effective at lower concentrations than drugs
      of the benzimidazole class. Therefore, these data strongly suggest that AZD0865
      has great potential as a fast-acting, low-dose inhibitor of acid secretion.

PMID- 16798726
TI  - Intestinal barrier failure during experimental necrotizing enterocolitis:
      protective effect of EGF treatment.
AB  - Necrotizing enterocolitis (NEC) is the most common intestinal disease of
      premature infants. Although increased mucosal permeability and altered epithelial
      structure have been associated with many intestinal disorders, the role of
      intestinal barrier function in NEC pathogenesis is currently unknown. We
      investigated the structural and functional changes of the intestinal barrier in a
      rat model of NEC. In addition, the effect of EGF treatment on intestinal barrier
      function was evaluated. Premature rats were divided into three groups: dam fed
      (DF), formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC
      + EGF); all groups were exposed to asphyxia/cold stress to develop NEC.
      Intestinal permeability, goblet cell density, mucin production, and composition
      of tight junction (TJ) proteins were evaluated in the terminal ileum, the site of
      NEC injury, and compared with the proximal jejunum, which was unaffected by NEC.
      Animals with NEC had significantly increased intestinal paracellular permeability
      compared with DF pups. Ileal goblet cell morphology, mucin production, and TJ
      composition were altered in animals with NEC. EGF treatment significantly
      decreased intestinal paracellular permeability, increased goblet cell density and
      mucin production, and normalized expression of two major TJ proteins, occludin
      and claudin-3, in the ileum. In conclusion, experimental NEC is associated with
      disruption of the intestinal barrier. EGF treatment maintains intestinal
      integrity at the site of injury by accelerating goblet cell maturation and mucin
      production and normalizing expression of TJ proteins, leading to improved
      intestinal barrier function.

PMID- 16798728
TI  - Rac1 mediates intestinal epithelial cell apoptosis via JNK.
AB  - Apoptosis plays a key role in the maintenance of a constant cell number and a low
      incidence of cancer in the mucosa of the intestine. Although the small GTPase
      Rac1 has been established as an important regulator of migration of intestinal
      epithelial cells, whether Rac1 is also involved in apoptosis is unclear. The
      present study tested the hypothesis that Rac1 mediates TNF-alpha-induced
      apoptosis in IEC-6 cells. Rac1 is activated during TNF-alpha-induced apoptosis as
      judged by the level of GTP-Rac1, the level of microsomal membrane-associated
      Rac1, and lamellipodia formation. Although expression of constitutively active
      Rac1 does not increase apoptosis in the basal condition, inhibition of Rac1
      either by NSC-23766 (Rac1 inhibitor) or expression of dominant negative Rac1
      protects cells from TNF-alpha-induced apoptosis by inhibiting caspase-3, -8, and 
      9 activities. Inhibition of Rac1 before the administration of apoptotic stimuli
      significantly prevents TNF-alpha-induced activation of JNK1/2, the key
      proapoptotic regulator in IEC-6 cells. Inhibition of Rac1 does not modulate TNF
      alpha-induced ERK1/2 and Akt activation. Inhibition of ERK1/2 and Akt activity by
      U-0126 and LY-294002, respectively, increased TNF-alpha-induced apoptosis.
      However, inhibition of Rac1 significantly decreased apoptosis in the presence of
      ERK1/2 and Akt inhibitors, similar to the effect observed with NSC-23766 alone in
      response to TNF-alpha. Thus, Rac1 inhibition protects cells independently of
      ERK1/2 and Akt activation during TNF-alpha-induced apoptosis. Although p38 MAPK
      is activated in response to TNF-alpha, inhibition of p38 MAPK did not decrease
      apoptosis. Rac1 inhibition did not alter p38 MAPK activity. Thus, these results
      indicate that Rac1 mediates apoptosis via JNK and plays a key role in
      proapoptotic pathways in intestinal epithelial cells.

PMID- 16798727
TI  - Role of enteric glia in intestinal physiology: effects of the gliotoxin
      fluorocitrate on motor and secretory function.
AB  - The role of enteric glia in gastrointestinal physiology remains largely
      unexplored. We examined the actions of the gliotoxin fluorocitrate (FC) on
      intestinal motility, secretion, and inflammation after assessing its efficacy and
      specificity in vitro. FC (100 microM) caused a significant decrease in the
      phosphorylation of the glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diaz-4
      yl)amino]-2-deoxyglucose in enteric glial cultures and a reduction in glial
      uptake of the fluorescent dipeptide Ala-Lys-7-amino-4-methylcoumarin-3-acetic
      acid in both the ileum and colon. Dipeptide uptake by resident murine macrophages
      or guinea pig myenteric neurons was unaffected by FC. Incubation of isolated
      guinea pig ileal segments with FC caused a specific and significant increase in
      glial expression of the phosphorylated form of ERK-1/2. Disruption of enteric
      glial function with FC in mice reduced small intestinal motility in vitro,
      including a significant decrease in basal tone and the amplitude of contractility
      in response to electrical field stimulation. Mice treated with 10 or 20
      micromol/kg FC twice daily for 7 days demonstrated a concentration-dependent
      decrease in small intestinal transit. In contrast, no changes in colonic transit
      or ion transport in vitro were observed. There were no changes in glial or
      neuronal morphology, any signs of inflammation in the FC-treated mice, or any
      change in the number of myenteric nitric oxide synthase-expressing neurons. We
      conclude that FC treatment causes enteric glial dysfunction, without causing
      intestinal inflammation. Our data suggest that enteric glia are involved in the
      modulation of enteric neural circuits underlying the regulation of intestinal
      motility.

PMID- 16798729
TI  - A carboxyl-terminal hydrophobic interface is critical to sodium channel function.
      Relevance to inherited disorders.
AB  - Perturbation of sodium channel inactivation, a finely tuned process that
      critically regulates the flow of sodium ions into excitable cells, is a common
      functional consequence of inherited mutations associated with epilepsy, skeletal
      muscle disease, autism, and cardiac arrhythmias. Understanding the structural
      basis of inactivation is key to understanding these disorders. Here we identify a
      novel role for a structural motif in the COOH terminus of the heart NaV1.5 sodium
      channel in determining channel inactivation. Structural modeling predicts an
      interhelical hydrophobic interface between paired EF hands in the proximal region
      of the NaV1.5 COOH terminus. The predicted interface is conserved among almost
      all EF hand-containing proteins and is the locus of a number of disease
      associated mutations. Using the structural model as a guide, we provide
      biochemical and biophysical evidence that the structural integrity of this
      interface is necessary for proper Na+ channel inactivation gating. We thus
      demonstrate a novel role of the sodium channel COOH terminus structure in the
      control of channel inactivation and in pathologies caused by inherited mutations
      that disrupt it.

PMID- 16798730
TI  - Topoisomerase action on short DNA duplexes reveals requirements for gate and
      transfer DNA segments.
AB  - Type II topoisomerases change DNA topology by passage of one DNA duplex (the
      transfer, T-segment) through a transient double-stranded break in another (the
      gate, G-segment). Here we monitor the passage between short double-stranded DNA
      segments within long single-stranded DNA circles that leads to catenation of the
      circles. To facilitate catenation, the circles were brought into close proximity
      using a tethering oligonucleotide, which was removed after the reaction was
      complete. We varied the length and the composition of the reacting DNA segments.
      The minimal DNA duplex length at which we detected catenation was 50-60 bp for
      DNA gyrase and 40 bp for topoisomerase IV (Topo IV). For Topo IV, catenation was
      observed when one, but not both, of the DNA-DNA duplexes was replaced by a DNA
      RNA duplex. Topo IV cleaved the DNA-DNA duplex, but not the DNA-RNA duplex
      implying that the DNA-RNA duplex can be a T-segment but not a G-segment.

PMID- 16798731
TI  - The circadian clock within the cardiomyocyte is essential for responsiveness of
      the heart to fatty acids.
AB  - Cells/organs must respond both rapidly and appropriately to increased fatty acid
      availability; failure to do so is associated with the development of skeletal
      muscle and hepatic insulin resistance, pancreatic beta-cell dysfunction, and
      myocardial contractile dysfunction. Here we tested the hypothesis that the
      intrinsic circadian clock within the cardiomyocytes of the heart allows rapid and
      appropriate adaptation of this organ to fatty acids by investigating the
      following: 1) whether circadian rhythms in fatty acid responsiveness persist in
      isolated adult rat cardiomyocytes, and 2) whether manipulation of the circadian
      clock within the heart, either through light/dark (L/D) cycle or genetic
      disruptions, impairs responsiveness of the heart to fasting in vivo. We report
      that both the intramyocellular circadian clock and diurnal variations in fatty
      acid responsiveness observed in the intact rat heart in vivo persist in adult rat
      cardiomyocytes. Reversal of the 12-h/12-h L/D cycle was associated with a re
      entrainment of the circadian clock within the rat heart, which required 5-8 days
      for completion. Fasting rats resulted in the induction of fatty acid-responsive
      genes, an effect that was dramatically attenuated 2 days after L/D cycle
      reversal. Similarly, a targeted disruption of the circadian clock within the
      heart, through overexpression of a dominant negative CLOCK mutant, severely
      attenuated induction of myocardial fatty acid-responsive genes during fasting.
      These studies expose a causal relationship between the circadian clock within the
      cardiomyocyte with responsiveness of the heart to fatty acids and myocardial
      triglyceride metabolism.

PMID- 16798732
TI  - Toll-like receptor-2 is essential for the development of palmitate-induced
      insulin resistance in myotubes.
AB  - Fatty acids can activate proinflammatory pathways leading to the development of
      insulin resistance, but the mechanism is undiscovered. Toll like receptor 2
      (TLR2) recognizes lipids, activates proinflammatory pathways, and is genetically
      associated with inflammatory diseases. This study aimed to examine the role of
      TLR2 in palmitate-induced insulin resistance in C2C12 myotubes. Treatment with
      palmitate rapidly induced the association of myeloid differentiation factor 88
      (MyD88) with the TLR2 receptor, activated the stress-linked kinases p38, JNK, and
      protein kinase C, induced degradation of IkappaBalpha, and increased NF-kappaB
      DNA binding. The activation of these pathways by palmitate was sensitive and
      temporally regulated and occurred within the upper physiologic range of saturated
      fatty acid concentrations in vivo, suggesting a receptor-mediated event and not
      simple lipotoxicity. When compared with an equimolar concentration of palmitate,
      fibroblast-stimulating lipopeptide-1, a known TLR2 ligand, was a slightly more
      potent activator of signal transduction and interleukin (IL)-6 production.
      Palmitate inhibited insulin signal transduction in C2C12 cells beginning 1-2 h
      after exposure and reached a maximum at 12-16 h. An antagonist TLR2 antibody, mAb
      2.5, led to a 50-60% decrease in palmitate-induced IL-6 production and partially
      restored insulin signal transduction, whereas an isotype-matched control antibody
      had no effect. RNA interference-mediated inhibition of TLR2 and MyD88 expression
      in C2C12 muscle cells resulted in a near complete inhibition of palmitate-induced
      insulin resistance and IL-6 production. This study provides strong evidence that
      TLR2 mediates the initial events of fatty acid-induced insulin resistance in
      muscle.

PMID- 16798733
TI  - Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac
      postnatal hypertrophic growth.
AB  - Postnatal cardiac hypertrophies have traditionally been classified into
      physiological or pathological hypertrophies. Both of them are induced by
      hemodynamic load. Cardiac postnatal hypertrophic growth is regarded as a part of
      the cardiac maturation process that is independent of the cardiac working load.
      However, the functional significance of this biological event has not been
      determined, mainly because of the difficulty in creating an experimental
      condition for testing the growth potential of functioning heart in the absence of
      hemodynamic load. Recently, we generated a novel transgenic mouse model (alphaMHC
      BMP10) in which the cardiac-specific growth factor bone morphogenetic protein 10
      (BMP10) is overexpressed in postnatal myocardium. These alphaMHC-BMP10 mice
      appear to have normal cardiogenesis throughout embryogenesis, but develop to
      smaller hearts within 6 weeks after birth. alphaMHC-BMP10 hearts are about half
      the normal size with 100% penetrance. Detailed morphometric analysis of
      cardiomyocytes clearly indicated that the compromised cardiac growth in alphaMHC
      BMP10 mice was solely because of defect in cardiomyocyte postnatal hypertrophic
      growth. Physiological analysis further demonstrated that the responses of these
      hearts to both physiological (e.g. exercise-induced hypertrophy) and pathological
      hypertrophic stimuli remain normal. In addition, the alphaMHC-BMP10 mice develop
      subaortic narrowing and concentric myocardial thickening without obstruction by
      four weeks of age. Systematic analysis of potential intracellular pathways
      further suggested a novel genetic pathway regulating this previously undefined
      cardiac postnatal hypertrophic growth event. This is the first demonstration that
      cardiac postnatal hypertrophic growth can be specifically modified genetically
      and dissected out from physiological and pathological hypertrophies.

PMID- 16798734
TI  - Identification of common transcriptional regulatory elements in interleukin-17
      target genes.
AB  - Interleukin (IL)-17 is the founding member of a novel family of inflammatory
      cytokines. Although produced by T cells, IL-17 activates genes and signals
      typical of innate immune mediators such as tumor necrosis factor (TNF)-alpha and
      IL-1beta. Most IL-17 target genes characterized to date are cytokines or
      neutrophil-attractive chemokines. Our recent microarray studies identified an
      acute phase response gene, 24p3/lipocalin 2, as a novel IL-17-induced gene. Here
      we describe a detailed analysis of the 24p3 promoter. We find that, unlike
      cytokine or chemokine gene target genes, 24p3 is regulated primarily at the level
      of transcription rather than mRNA stability and that synergy between IL-17 and
      TNFalpha occurs at the level of the 24p3 promoter. Two key transcription factor
      binding sites (TFBS) were identified, corresponding to NF-kappaB and
      CCAAT/enhancer-binding protein (C/EBP). Deletion of either site eliminated 24p3
      promoter activity in response to IL-17. These findings were strikingly similar to
      the IL-6 promoter, where IL-17-mediated regulation of both NF-kappaB and C/EBP is
      essential. To determine whether joint use of NF-kappaB and C/EBP is common to all
      IL-17 target genes, we performed a computational analysis on 18 well documented
      IL-17 target promoters to assess statistical enrichment of specific TFBSs.
      Indeed, NF-kappaB and C/EBP sites were over-represented in these genes, as were
      AP1 and OCT1 sites. Moreover, these promoters fell into three definable
      subcategories based on TFBS location and usage. Analysis of IL-17 target gene
      regulation is key for understanding this important host-defense molecule and also
      contributes to an understanding of upstream signaling mechanisms used by IL-17,
      either alone or in concert with TNFalpha.

PMID- 16798735
TI  - Granzyme B proteolyzes receptors important to proliferation and survival, tipping
      the balance toward apoptosis.
AB  - Granzyme B is critical to the ability of natural killer cells and cytotoxic T
      lymphocytes to induce efficient cell death of virally infected or tumor cell
      targets. Although granzyme B can cleave and activate caspases to induce
      apoptosis, granzyme B can also cause caspase-independent cell death. Thirteen
      prospective granzyme B substrates were identified from a cDNA expression-cleavage
      screen, including Hsp70, Notch1, fibroblast growth factor receptor-1 (FGFR1),
      poly-A-binding protein, cAbl, heterogeneous nuclear ribonucleoprotein H', Br140,
      and intersectin-1. Validation revealed that Notch1 is a substrate of both
      granzyme B and caspases, whereas FGFR1 is a caspase-independent substrate of
      granzyme B. Proteolysis of FGFR1 in prostate cancer cells has functionally
      relevant consequences that indicate its cleavage may be advantageous for granzyme
      B to kill prostate cancer cells. Therefore, granzyme B not only activates pro
      death functions within a target, but also has a previously unidentified role in
      inactivating pro-growth signals to cause cell death.

PMID- 16798736
TI  - Activation of mammalian target of rapamycin (mTOR) by insulin is associated with
      stimulation of 4EBP1 binding to dimeric mTOR complex 1.
AB  - Insulin stimulates protein synthesis by promoting phosphorylation of the eIF4E
      binding protein, 4EBP1. This effect is rapamycin-sensitive and mediated by
      mammalian target of rapamycin (mTOR) complex 1 (mTORC1), a signaling complex
      containing mTOR, raptor, and mLST8. Here we demonstrate that insulin produces a
      stable increase in the kinase activity of mTORC1 in 3T3-L1 adipocytes. The
      response was associated with a marked increase in 4EBP1 binding to raptor in
      mTORC1, and it was abolished by disrupting the TOR signaling motif in 4EBP1. The
      stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred
      rapidly and at physiological concentrations of insulin, and both effects required
      an intact mTORC1. Results of experiments involving size exclusion chromatography
      and coimmunoprecipitation of epitope-tagged subunits provide evidence that the
      major insulin-responsive form is dimeric mTORC1, a structure containing two
      heterotrimers of mTOR, raptor, and mLST8.

PMID- 16798737
TI  - The crystal structure of a collagen-like polypeptide with 3(S)-hydroxyproline
      residues in the Xaa position forms a standard 7/2 collagen triple helix.
AB  - Collagen has a triple helical structure comprising strands with a repeating Xaa
      Yaa-Gly sequence. L-Proline (Pro) and 4(R)-hydroxyl-L-proline (4(R)Hyp) residues
      are found most frequently in the Xaa and Yaa positions. However, in natural
      collagen, 3(S)-hydroxyl-L-proline (3(S)Hyp) occurs in the Xaa positions to
      varying extents and is most common in collagen types IV and V. Although 4(R)Hyp
      residues in the Yaa positions have been shown to be critical for the formation of
      a stable triple helix, the role of 3(S)Hyp residues in the Xaa position is not
      well understood. Indeed, recent studies have demonstrated that the presence of
      3(S)Hyp in the Xaa positions of collagen-like peptides actually has a
      destabilizing effect relative to peptides with Pro in these locations. Whether
      this destabilization is reflected in a local unfolding or in other structural
      alterations of the collagen triple helix is unknown. Thus, to determine what
      effect the presence of 3(S)Hyp residues in the Xaa positions has on the overall
      conformation of the collagen triple helix, we determined the crystal structure of
      the polypeptide H-(Gly-Pro-4(R)Hyp)3-(Gly-3(S)Hyp-4(R)Hyp)2-(Gly-Pro-4(R)Hyp)4-OH
      to 1.80 A resolution. The structure shows that, despite the presence of the
      3(S)Hyp residues, the peptide still adopts a typical 7/2 superhelical symmetry
      similar to that observed in other collagen structures. The puckering of the Xaa
      position 3(S)Hyp residues, which are all down (Cgamma-endo), and the varphi/psi
      dihedral angles of the Xaa 3(S)Hyp residues are also similar to those of typical
      collagen Pro Xaa residues. Thus, the presence of 3(S)Hyp in the Xaa positions
      does not lead to large structural alterations in the collagen triple helix.

PMID- 16798738
TI  - State-dependent conformations of the translocation pathway in the tyrosine
      transporter Tyt1, a novel neurotransmitter:sodium symporter from Fusobacterium
      nucleatum.
AB  - The gene of a novel prokaryotic member (Tyt1) of the neurotransmitter:sodium
      symporter (NSS) family has been cloned from Fusobacterium nucleatum. In contrast
      to eukaryotic and some prokaryotic NSSs, which contain 12 transmembrane domains
      (TMs), Tyt1 contains only 11 TMs, a characteristic shared by approximately 70% of
      prokaryotic NSS homologues. Nonetheless upon heterologous expression in an
      engineered Escherichia coli host, Tyt1 catalyzes robust Na+-dependent, highly
      selective l-tyrosine transport. Genetic engineering of Tyt1 variants devoid of
      cysteines or with individually retained endogenous cysteines at positions 18 or
      238, at the cytoplasmic ends of TM1 and TM6, respectively, preserved normal
      transport activity. Whereas cysteine-less Tyt1 was resistant to the inhibitory
      effect of sulfhydryl-alkylating reagents, N-ethylmaleimide inhibited transport by
      Tyt1 variants containing either one or both of the endogenous cysteines, and this
      inhibition was altered by the substrates sodium and tyrosine, consistent with
      substrate-induced dynamics in the transport pathway. Our findings support a
      binding model of Tyt1 function in which an ordered sequence of substrate-induced
      structural changes reflects distinct conformational states of the transporter.
      This work identifies Tyt1 as the first functional bacterial NSS member putatively
      consisting of only 11 TMs and shows that Tyt1 is a suitable model for the study
      of NSS dynamics with relevance to structure/function relationships of human NSSs,
      including the dopamine, norepinephrine, serotonin, and gamma-aminobutyric acid
      transporters.

PMID- 16798739
TI  - Protein kinase Czeta is up-regulated in osteoarthritic cartilage and is required
      for activation of NF-kappaB by tumor necrosis factor and interleukin-1 in
      articular chondrocytes.
AB  - Protein kinase Czeta (PKCzeta) is an intracellular serine/threonine protein
      kinase that has been implicated in the signaling pathways for certain
      inflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor
      alpha (TNF-alpha), in some cell types. A study of gene expression in articular
      chondrocytes from osteoarthritis (OA) patients revealed that PKCzeta is
      transcriptionally up-regulated in human OA articular cartilage clinical samples.
      This finding led to the hypothesis that PKCzeta may be an important signaling
      component of cytokine-mediated cartilage matrix destruction in articular
      chondrocytes, believed to be an underlying factor in the pathophysiology of OA.
      IL-1 treatment of chondrocytes in culture resulted in rapidly increased
      phosphorylation of PKCzeta, implicating PKCzeta activation in the signaling
      pathway. Chondrocyte cell-based assays were used to evaluate the contribution of
      PKCzeta activity in NF-kappaB activation and extracellular matrix degradation
      mediated by IL-1, TNF, or sphingomyelinase. In primary chondrocytes, IL-1 and TNF
      alpha caused an increase in NF-kappaB activity resulting in induction of
      aggrecanase-1 and aggrecanase-2 expression, with consequent increased
      proteoglycan degradation. This effect was blocked by the pan-specific PKC
      inhibitors RO 31-8220 and bisindolylmaleimide I, partially blocked by Go 6976,
      and was unaffected by the PKCzeta-sparing inhibitor calphostin C. A cell
      permeable PKCzeta pseudosubstrate peptide inhibitor was capable of blocking
      TNFand IL-1-mediated NF-kappaB activation and proteoglycan degradation in
      chondrocyte pellet cultures. In addition, overexpression of a dominant negative
      PKCzeta protein effectively prevented cytokine-mediated NF-kappaB activation in
      primary chondrocytes. These data implicate PKCzeta as a necessary component of
      the IL-1 and TNF signaling pathways in chondrocytes that result in catabolic
      destruction of extracellular matrix proteins in osteoarthritic cartilage.

PMID- 16798740
TI  - Homophilic interactions of Tetraspanin CD151 up-regulate motility and matrix
      metalloproteinase-9 expression of human melanoma cells through adhesion-dependent
      c-Jun activation signaling pathways.
AB  - The tetraspanin membrane protein CD151 has been suggested to regulate cancer
      invasion and metastasis by initiating signaling events. The CD151-mediated
      signaling pathways involved in this regulation remain to be revealed. In this
      study, we found that stable transfection of CD151 into MelJuSo human melanoma
      cells lacking CD151 expression significantly increased cell motility, matrix
      metalloproteinase-9 (MMP-9) expression, and invasiveness. The enhancement of cell
      motility and MMP-9 expression by CD151 overexpression was abrogated by inhibitors
      and small interfering RNAs targeted to focal adhesion kinase (FAK), Src, p38
      MAPK, and JNK, suggesting an essential role of these signaling components in
      CD151 signaling pathways. Also, CD151-induced MMP-9 expression was shown to be
      mediated by c-Jun binding to AP-1 sites in the MMP-9 gene promoter, indicating AP
      1 activation by CD151 signaling pathways. Meanwhile, CD151 was found to be
      associated with alpha(3)beta(1) and alpha(6)beta(1) integrins in MelJuSo cells,
      and activation of associated integrins was a prerequisite for CD151-stimulated
      MMP-9 expression and activation of FAK, Src, p38 MAPK, JNK, and c-Jun.
      Furthermore, CD151 on one cell was shown to bind to neighboring cells expressing
      CD151, suggesting that CD151 is a homophilic interacting protein. The homophilic
      interactions of CD151 increased motility and MMP-9 expression of CD151
      transfected MelJuSo cells, along with FAK-, Src-, p38 MAPK-, and JNK-mediated
      activation of c-Jun in an adhesion-dependent manner. Furthermore, C8161 melanoma
      cells with endogenous CD151 were also shown to respond to homophilic CD151
      interactions for the induction of adhesion-dependent activation of FAK, Src, and
      c-Jun. These results suggest that homophilic interactions of CD151 stimulate
      integrin-dependent signaling to c-Jun through FAK-Src-MAPKs pathways in human
      melanoma cells, leading to enhanced cell motility and MMP-9 expression.

PMID- 16798741
TI  - Reishi polysaccharides induce immunoglobulin production through the TLR4/TLR2
      mediated induction of transcription factor Blimp-1.
AB  - The polysaccharides of Ganoderma lucidum (Reishi) possess immunomodulation
      activities; however, their mode of molecular action in regulating each cellular
      subset in the immune system is still not clear. Here, we investigate the function
      of the main polysaccharide fraction of Reishi (Reishi-F3) in B lymphocyte
      activation/differentiation. We find that Reishi-F3 causes mouse splenic B cell
      activation and differentiation to IgM-secreting plasma cells, and the process
      depends on Reishi-F3-mediated induction of Blimp-1, a master regulator capable of
      triggering the changes of a cascade of gene expression during plasmacytic
      differentiation. In human peripheral B lymphocytes, although Reishi-F3 fails to
      induce their activation, it is able to enhance antibody secretion, which is
      associated with Blimp-1 mRNA induction. The function of Reishi-F3 depends on the
      Toll-like receptors TLR4/TLR2 as neutralizing antibodies against TLR4/TLR2 block
      Reishi-F3-mediated induction of Blimp-1 mRNA and Ig secretion. We have shown that
      interaction of Reishi-F3 with TLR4/TLR2 followed by signaling through p38 MAPK is
      involved in the induction of Blimp-1 mRNA, whereas signaling through ERK, p38
      MAPK, JNK, and IKK complex is involved in Reishi-F3-mediated Ig secretion.
      Furthermore, the differential mechanism of Reishi-F3 in mouse and human B cell
      activation is probably due to the presence of Blimp-1 regulatory site in human
      CD86 promoter. These results establish the signaling and molecular mechanisms of
      Reishi-F3 on promoting antibody secretion.

PMID- 16798743
TI  - Identification of cell cycle regulatory genes as principal targets of p53
      mediated transcriptional repression.
AB  - Historically, most studies attribute p53 function to the transactivation of
      target genes. That p53 can selectively repress genes to affect a cellular
      response is less widely appreciated. Available evidence suggests that repression
      is important for p53-induced apoptosis and cell cycle arrest. To better establish
      the scope of p53-repressed target genes and the cellular processes they may
      affect, a global expression profiling strategy was used to identify p53
      responsive genes following adenoviral p53 gene transfer (Ad-p53) in PC3 prostate
      cancer cells. A total of 111 genes, 0.77% of the 14,500 genes represented on the
      Affymetrix U133A microarray, were repressed more than 2-fold (p < or = 0.05).
      Validation of the array data, using reverse transcription-PCR of 20 randomly
      selected genes, yielded a confirmation rate of >95.5% for the complete data set.
      Functional over-representation analysis revealed that cell cycle regulatory genes
      exhibited a highly significant enrichment (p < or = 5 x 10(-28)) within the
      transrepressed targets. 41% of the repressed targets are cell cycle regulators. A
      subset of these genes exhibited repression following DNA damage, preceding cell
      cycle arrest, in LNCaP cells. The use of a p53 small interfering RNA strategy in
      LNCaP cells and the use of p53-null cell lines demonstrated that this repression
      is p53-dependent. These findings identify a set of genes not known previously to
      be down-regulated by p53 and indicate that p53-induced cell cycle arrest is a
      function of not only the transactivation of cell cycle inhibitors (e.g. p21) but
      also the repression of targets that regulate proliferation at several distinct
      phases of the cell cycle.

PMID- 16798742
TI  - Intrinsic kinase activity and SQ/TQ domain of Chk2 kinase as well as N-terminal
      domain of Wip1 phosphatase are required for regulation of Chk2 by Wip1.
AB  - The anti-oncogenic Chk2 kinase plays a crucial role in DNA damage-induced cell
      cycle checkpoint regulation. Recently, we have shown that Chk2 associates with
      the oncogenic Wip1 (PPM1D) phosphatase and that Wip1 acts as a negative regulator
      of Chk2 during DNA damage response by dephosphorylating phosphorylated Thr-68 in
      activated Chk2 (Fujimoto, H., Onishi, N., Kato, N., Takekawa, M., Xu, X. Z.,
      Kosugi, A., Kondo, T., Imamura, M., Oishi, I., Yoda, A., and Minami, Y. (2006)
      Cell Death Differ. 13, 1170-1180). Here, we performed structure-function analyses
      of Chk2 and Wip1 by using a series of deletion or amino acid-substituted mutant
      proteins of Chk2 and Wip1. We show that nuclear localization of both Chk2 and
      Wip1 is required for their association in cultured cells and that the serine
      glutamine (SQ)/threonine-glutamine (TQ) domain of Chk2, containing Thr-68, and
      the N-terminal domain of Wip1, comprising about 100 amino acids, are necessary
      and sufficient for the association of both molecules. However, it was found that
      an intrinsic kinase activity of Chk2, but not phosphatase activity of Wip1, is
      required for the association of fulllength Chk2 and Wip1. Interestingly, we also
      show that the mutant Wip1 proteins, bearing the N-terminal domain of Wip1 alone
      or lacking an intrinsic phosphatase activity, exhibit dominant negative effects
      on the functions of the wild-type Wip1, i.e. ectopic expression of either of
      these Wip1 mutants inhibits dephosphorylation of Thr-68 in Chk2 by Wip1 and anti
      apoptotic function of Wip1. These results provide a molecular basis for
      developing novel anti-cancer drugs, targeting oncogenic Wip1 phosphatase.

PMID- 16798744
TI  - Hemicentin assembly in the extracellular matrix is mediated by distinct
      structural modules.
AB  - Hemicentins are conserved extracellular matrix proteins characterized by a single
      von Willebrand A (VWA) domain at the amino terminus, a long stretch (>40) of
      tandem immunoglobulin domains, multiple tandem epidermal growth factors (EGFs),
      and a single fibulin-like carboxyl-terminal module. In Caenorhabditis elegans,
      hemicentin is secreted from muscle and gonadal leader cells and assembles at
      multiple locations into discrete tracks that constrict broad regions of cell
      contact into adhesive and flexible line-shaped junctions. To determine hemicentin
      domains critical for function and assembly, we have expressed fragments of
      hemicentin as GFP tagged fusion proteins in C. elegans. We find that a hemicentin
      fragment containing the VWA domain can target to multiple assembly sites when
      expressed under the control of either endogenous hemicentin regulatory sequences
      or the muscle-specific unc-54 promoter. A hemicentin fragment containing the EGF
      and fibulin-like carboxyl-terminal modules can co-assemble with existing
      hemicentin polymers in wild-type animals but has no detectable function in the
      absence of endogenous hemicentin. The data suggest that the VWA domain is a cell
      binding domain whose function is to target hemicentin to sites of assembly and
      the EGF/fibulin-like carboxyl-terminal modules constitute an assembly domain that
      mediates direct interactions between hemicentin monomers during the hemicentin
      assembly process.

PMID- 16798745
TI  - Systemically administered bone morphogenetic protein-6 restores bone in aged
      ovariectomized rats by increasing bone formation and suppressing bone resorption.
AB  - Although recombinant human bone morphogenetic proteins (BMPs) are used locally
      for treating bone defects in humans, their systemic effect on bone augmentation
      has not been explored. We have previously demonstrated that demineralized bone
      (DB) from ovariectomized (OVX) rats cannot induce bone formation when implanted
      ectopically at the subcutaneous site. Here we showed in vitro that 17beta
      estradiol (E2) specifically induced expression of Bmp6 mRNA in MC3T3-E1
      preosteoblastic cells and that bone extracts from OVX rats lack BMPs. Next we
      demonstrated that 125I-BMP-6 administered systemically accumulated in the
      skeleton and also restored the osteoinductive capacity of ectopically implanted
      DB from OVX rats. BMP-6 applied systemically to aged OVX rats significantly
      increased bone volume and mechanical characteristics of both the trabecular and
      cortical bone, the osteoblast surface, serum osteocalcin and osteoprotegerin
      levels, and decreased the osteoclast surface, serum C-telopeptide, and
      interleukin-6. E2 was significantly less effective, and was not synergistic with
      BMP-6. Animals that discontinued BMP-6 therapy maintained bone mineral density
      gains for another 12 weeks. BMP-6 increased in vivo the bone expression of Acvr
      1, Bmpr1b, Smad5, alkaline phosphatase, and collagen type I and decreased
      expression of Bmp3 and BMP antagonists, chordin and cerberus. These results show,
      for the first time, that systemically administered BMP-6 restores the bone
      inductive capacity, microarchitecture, and quality of the skeleton in
      osteoporotic rats.

PMID- 16798746
TI  - Raloxifene increases proliferation and up-regulates telomerase activity in human
      umbilical vein endothelial cells.
AB  - Vascular endothelial senescence is involved in human atherosclerosis. Telomerase
      activity is known to be critical in cellular senescence and its level is
      modulated by regulation of telomerase catalytic subunit (telomerase reverse
      transcriptase (TERT)) at both the transcriptional and post-transcriptional
      levels. Since the cardioprotective effect of estrogen itself has not been ruled
      out, we examined that of raloxifene, which has been classified as a selective
      estrogen receptor modulator, on the proliferation and telomerase activity of
      human umbilical vein endothelial cells (HUVECs). Raloxifene, like estrogen,
      clearly induced the telomerase activity and human TERT (hTERT) expression via
      estrogen receptor (ER) alpha and ERbeta. Treatment with raloxifene for 5 days
      significantly induced cell growth, and either cotreatment with a telomerase
      inhibitor, 3'-azido-3'-deoxythymidine, or transfection with hTERT-specific small
      interfering RNA significantly attenuated the raloxifene-induced cell growth.
      Raloxifene also induced the phosphorylation of Akt, and pretreatment with a
      phosphatidylinositol 3-kinase inhibitor, LY294002, significantly attenuated the
      raloxifene-induced telomerase activity. In addition, raloxifene induced both the
      phosphorylation of hTERT and IkappaB. Moreover, cotreatment with an IkappaBalpha
      phosphorylation inhibitor, BAY-11-7082, or a specific NFkappaB nuclear
      translocation inhibitor, SN50, significantly attenuated the raloxifene-induced
      telomerase activity and the association of NFkappaB with hTERT. These results
      show that raloxifene induced the up-regulation of telomerase activity not only by
      the transcriptional regulation of hTERT but also by post-translational regulation
      of the phosphorylation of Akt and hTERT and the association of hTERT with
      NFkappaB in HUVECs. Thus, the up-regulation of telomerase activity in vascular
      endothelial cells might be one mechanism contributing to the potential
      atheroprotective effect of raloxifene.

PMID- 16798747
TI  - Differential susceptibility of HIV-1 reverse transcriptase to inhibition by RNA
      aptamers in enzymatic reactions monitoring specific steps during genome
      replication.
AB  - Nucleic acid aptamers to HIV-1 reverse transcriptase (RT) are potent inhibitors
      of DNA polymerase function in vitro, and they have been shown to inhibit viral
      replication when expressed in cultured T-lymphoid lines. We monitored RT
      inhibition by five RNA pseudoknot RNA aptamers in a series of biochemical assays
      designed to mimic discrete steps of viral reverse transcription. Our results
      demonstrate potent aptamer inhibition (IC50 values in the low nanomolar range) of
      all RT functions assayed, including RNA- and DNA-primed DNA polymerization,
      strand displacement synthesis, and polymerase-independent RNase H activity.
      Additionally, we observe differences in the time dependence of aptamer
      inhibition. Polymerase-independent RNase H activity is the most resistant to long
      term aptamer suppression, and RNA-dependent DNA polymerization is the most
      susceptible. Finally, when DNA polymerization was monitored in the presence of an
      RNA aptamer in combination with each of four different small molecule inhibitors,
      significant synergy was observed between the aptamer and the two nucleoside
      analog RT inhibitors (azidothymidine triphosphate or ddCTP), whereas two non
      nucleoside analog RT inhibitors showed either weak synergy (efavirenz) or
      antagonism (nevirapine). Together, these results support a model wherein aptamers
      suppress viral replication by cumulative inhibition of RT at every stage of
      genome replication.

PMID- 16798748
TI  - Adenomatous polyposis coli (APC) differentially regulates beta-catenin
      phosphorylation and ubiquitination in colon cancer cells.
AB  - Most colorectal cancers have mutations of the adenomatous polyposis coli (APC)
      gene or the beta-catenin gene that stabilize beta-catenin and activate beta
      catenin target genes, leading ultimately to cancer. The molecular mechanisms of
      APC function in beta-catenin degradation are not completely known. APC binds beta
      catenin and is involved in the Axin complex, suggesting that APC regulates beta
      catenin phosphorylation. Some evidence also suggests that APC regulates beta
      catenin nuclear export. Here, we examine the effects of APC mutations on beta
      catenin phosphorylation, ubiquitination, and degradation in the colon cancer cell
      lines SW480, DLD-1, and HT29, each of which contains a different APC truncation.
      Although the current models suggest that beta-catenin phosphorylation should be
      inhibited by APC mutations, we detected significant beta-catenin phosphorylation
      in these cells. However, beta-catenin ubiquitination and degradation were
      inhibited in SW480 but not in DLD-1 and HT29 cells. The ubiquitination ofbeta
      catenin in SW480 cells can be rescued by exogenous expression of APC. The APC
      domains required for beta-catenin ubiquitination were analyzed. Our results
      suggest that APC regulates beta-catenin phosphorylation and ubiquitination by
      distinct domains and by separate molecular mechanisms.

PMID- 16798750
TI  - Comparison of a Salmonella typhimurium proteome defined by shotgun proteomics
      directly on an LTQ-FT and by proteome pre-fractionation on an LCQ-DUO.
AB  - Shotgun proteomics is rapidly becoming one of the most efficient and popular
      tools to examine protein expression in cells. Numerous laboratories now have a
      wide array of low- and high-performance mass spectrometry instrumentation
      necessary to complete proteome-wide projects. Often these laboratories have time
      and financial constraints that prohibit all projects from being conducted on high
      performance state-of-the-art mass spectrometers. Here, we compare shotgun
      proteomic results using a direct 'lyse, digest and analyse' approach on a high
      performance mass spectrometer (i.e. the LTQ-FT) with the results from a much
      lower-performance instrument (i.e. the LCQ-DUO) where, for the latter, various
      traditional protein pre-fractionation steps and gas-phase fractionation were used
      to increase the proteome coverage. Our results demonstrate that shotgun proteomic
      analyses conducted on the lower-performance LCQ-DUO mass spectrometer could
      adequately characterize a PhoP constitutive strain of Salmonella typhimurium if
      proteome pre-fractionation steps and gas-phase fractionation were included.

PMID- 16798751
TI  - Soft paternalism and the ethics of shared electronic patient records.

PMID- 16798752
TI  - The NHS programme for information technology.

PMID- 16798753
TI  - Changes in safety on England's roads: analysis of hospital statistics.
AB  - OBJECTIVE: To compare trends in the numbers of people with serious traffic
      injuries according to police statistics and hospital episode statistics (HES).
      DESIGN: Descriptive study based on two independent population based data sources.
      SETTING: Police statistics and hospital episode statistics in England. MAIN
      OUTCOME MEASURES: Rates of injury and death and their change over time reported
      in each data source, for 1996 to 2004. RESULTS: According to police statistics,
      rates of people killed or seriously injured on the roads fell consistently from
      85.9 per 100,000 in 1996 to 59.4 per 100,000 in 2004. Over the same time,
      however, hospital admission rates for traffic injuries were almost unchanged at
      90.0 in 1996 and 91.1 in 2004. Both datasets showed a significant reduction in
      rates of injury in children aged < or = 15, but the reduction in hospital
      admission rates was substantially less than the reduction shown in the police
      statistics. The definition of serious injury in police statistics includes every
      hospital admission; in each year, none the less, the number of admissions
      exceeded the number of injuries reported in the police system. CONCLUSIONS: The
      overall fall seen in police statistics for non-fatal road traffic injuries
      probably represents a fall in completeness of reporting of these injuries.

PMID- 16798754
TI  - Awareness of driving while sleepy and road traffic accidents: prospective study
      in GAZEL cohort.
AB  - OBJECTIVES: To examine the association between self assessed driving while sleepy
      and the risk of serious road traffic accidents (RTAs). DESIGN: Prospective cohort
      study. SETTING: France. PARTICIPANTS: 13 299 of the 19 894 living members of the
      GAZEL cohort, workers and recent retirees of a French national utility company
      followed up since 1989. MAIN OUTCOME MEASURES: Frequency of driving while sleepy
      in the previous 12 months, reported in 2001; rate ratios for serious RTAs in 2001
      3, estimated by using generalised linear Poisson regression models with time
      dependent covariates. RESULTS: The risk of serious RTAs increased proportionally
      with the frequency of self reported driving while sleepy. After adjustment for
      sociodemographic characteristics, driving behaviour variables, work conditions,
      retirement, medical conditions and treatments, depressive symptoms, and sleep
      disorders, the adjusted rate ratios of serious RTAs for participants who reported
      driving while sleepy in the previous 12 months "a few times" or "once a month or
      more often" were 1.5 (95% confidence interval 1.2 to 2.0) and 2.9 (1.3 to 6.3)
      respectively compared with those who reported not driving while sleepy over the
      same period. These associations were not explained by any reported sleep
      disorders. CONCLUSIONS: Self assessed driving while sleepy was a powerful
      predictor of serious RTAs, suggesting that drivers' awareness of their sleepiness
      while driving is not sufficient to prevent them from having RTAs. Messages on
      prevention should therefore focus on convincing sleepy drivers to stop driving
      and sleep before resuming their journey.

PMID- 16798755
TI  - Unsafe driving behaviour and four wheel drive vehicles: observational study.
AB  - OBJECTIVE: To assess the level of compliance with the new law in the United
      Kingdom mandating penalties for using a hand held mobile phone while driving, to
      compare compliance with this law with the one on the use of seat belts, and to
      compare compliance with these laws between drivers of four wheel drive vehicles
      and drivers of normal cars. DESIGN: Observational study with two phases-one
      within the "grace" period, the other starting one week after penalties were
      imposed on drivers using such telephones. SETTING: Three busy sites in London.
      PARTICIPANTS: Drivers of 38,182 normal cars and 2944 four wheel drive vehicles.
      MAIN OUTCOME MEASURES: Proportions of drivers seen to be using hand held mobile
      phones and not using seat belts. RESULTS: Drivers of four wheel drive vehicles
      were more likely than drivers of other cars to be seen using hand held mobile
      phones (8.2% v 2.0%) and not complying with the law on seat belts (19.5% v
      15.0%). Levels of non-compliance with both laws were slightly higher in the
      penalty phase of observation, and breaking one law was associated with increased
      likelihood of breaking the other. CONCLUSIONS: The level of non-compliance with
      the law on the use of hand held mobile phones by drivers in London is high, as is
      non-compliance with the law on seat belts. Drivers of four wheel drive vehicles
      were four times more likely than drivers of other cars to be seen using hand held
      mobile phones and slightly more likely not to comply with the law on seat belts.

PMID- 16798758
TI  - Randomized comparison between Ramp and Burst+ atrial antitachycardia pacing
      therapies in patients suffering from sinus node disease and atrial fibrillation
      and implanted with a DDDRP device.
AB  - AIMS: Atrial tachycardia and flutter frequently occur in association with atrial
      fibrillation and may be treated by overdrive pacing in patients who receive
      pacemakers with antitachycardia pacing (ATP) capabilities. The PITAGORA trial was
      a multi-centre, randomized, cross-over study aimed at comparing two different ATP
      modes for atrial tachyarrhythmia (AT) termination in patients suffering from
      sinus node disease (SND). METHODS AND RESULTS: One hundred and seventy-six
      patients (72 M, age 71+/-9 years) received a Medtronic AT500 pacemaker. All
      patients were on class IC or III antiarrhythmic drugs. After a 5-month
      observation period, 170 patients were randomized to either Ramp or Burst+ ATP
      therapy; 4 months later they crossed over. One hundred and fifty-seven patients
      completed the 13 months of follow-up; 114 (72.6%) suffered 6088 AT episodes. In
      75 patients, 1904 AT episodes were treated and 934 (49.1%) successfully
      terminated. The median value of individual patients' ATP efficacy was 60%. Burst+
      terminated 387 out of 873 AT episodes (44%) in 58 patients. Ramp terminated 547
      out of 1031 AT episodes (53%, P<0.001) in 56 patients. Ramp efficacy was
      significantly (P<0.01) and directly correlated with AT cycle length (ATCL),
      whereas Burst+ efficacy was not. Ramp showed higher (P<0.001) termination
      efficacy than Burst+ for ATCL >240 ms. Quality of life, as measured by the
      EuroQoL questionnaire, and number of symptoms significantly improved in the
      overall population. This improvement was significantly higher in patients with
      ATP efficacy >60%. CONCLUSION: In patients suffering from SND and AT, Ramp
      therapy shows higher termination efficacy than Burst+ therapy in AT episodes with
      ATCL >240 ms. Further studies are required to show the impact of ATP on clinical
      outcomes.

PMID- 16798756
TI  - Mortality after Staphylococcus aureus bacteraemia in two hospitals in
      Oxfordshire, 1997-2003: cohort study.
AB  - OBJECTIVE: To determine the incidence of methicillin resistant and methicillin
      sensitive Staphylococcus aureus (MRSA and MSSA) bacteraemia in inpatients and
      associated mortality within 30 days after diagnosis. DESIGN: Anonymised record
      linkage study of data from hospital information systems and microbiology
      databases. SETTING: Teaching hospital and district general hospital in
      Oxfordshire. PARTICIPANTS: Inpatients aged 18 or over admitted to a teaching
      hospital between 1 April 1997 and 31 March 2004 and to a district general
      hospital between 1 April 1999 and 31 March 2004. The main part of the study
      comprised 216 644 inpatients; patients admitted to haematology, nephrology, or
      oncology services were not included because most were managed as outpatients.
      OUTCOME MEASURES: Nosocomial MSSA and MRSA bacteraemia; death in hospital within
      30 days after bacteraemia. RESULTS: Rates of S aureus bacteraemia rose between
      1997 and 2003, and MRSA was responsible for this increase. Overall mortality 30
      days after bacteraemia was 29%. The crude odds ratio for death after MRSA
      bacteraemia compared with MSSA bacteraemia was 1.49 (95% confidence interval 0.99
      to 2.26). CONCLUSION: The spread of MRSA has greatly increased the overall number
      of cases of S aureus bacteraemia and has contributed to short term mortality
      after S aureus bacteraemia.

PMID- 16798759
TI  - Atrial tachyarrhythmia burden modelling by some electrophysiological parameters
      in pacemaker-recipient patients with Brady-Tachy syndrome.
AB  - AIMS: (1) To correlate atrial tachyarrhythmia (AT) burden of pacemaker-recipient
      Brady-Tachy syndrome (BTS) patients with a number of diagnostics-derived
      parameters after 1 month of DDD pacing; (2) to asses whether the activation of
      atrial overdrive or conventional rate-responsive pacing may affect relevant
      variables and their correlation. METHODS AND RESULTS: After 1 month of DDD
      pacing, rate-responsive function or persistent atrial overdrive was randomly
      activated for 3 months, in 92 BTS patients. Some pacemaker diagnostics parameters
      collected at 1- and 4-month follow-ups were included in multiple linear
      regression models, whose dependent variable was the Log transformation of AT
      burden and compared. With 1-month data, the only variables significantly
      correlating with Log AT burden were average (with a regression coefficient
      estimate of -0.07, P=0.02) and standard deviation (0.10, P=0.007) of atrial rate,
      mean premature atrial contraction (PAC) coupling interval (CI) (-0.005, P=0.001),
      frequency of PACs with CI<500 ms (1.30, P<10(-6)). Atrial pacing percentage (APP)
      and ventricular pacing percentage (VPP), PACs with CI>500 ms did not
      significantly correlate. Four-month data largely confirmed these results, except
      that in DDDR atrial rate average and standard deviation no longer correlated.
      Overdrive significantly increased APP and reduced PACs with CI>500 ms.
      CONCLUSION: AT burden showed significant dependence in DDD and during overdrive
      on atrial rate average and standard deviation. Highly premature PACs always
      significantly correlated with AT burden. Though increasing APP, which
      unexpectedly never correlated, overdrive could only reduce less premature PACs.

PMID- 16798760
TI  - Natriuretic peptides in patients with atrial fibrillation and advanced chronic
      heart failure: determinants and prognostic value of (NT-)ANP and (NT-pro)BNP.
AB  - AIMS: To study the determinants of natriuretic peptides in advanced chronic heart
      failure (CHF) patients with and without atrial fibrillation (AF) and to evaluate
      the prognostic value of natriuretic peptides in AF compared with sinus rhythm
      patients with advanced CHF. METHODS AND RESULTS: The study group comprised 354
      advanced CHF patients [all New York Heart Association (NYHA) III/IV], including
      76 AF patients. AF patients were older (70+/-7 vs. 67+/-8; P=0.01), and non
      ischaemic CHF was more common (42 vs. 19%; P=0.002) than in sinus rhythm
      patients, but left-ventricular ejection fraction was comparable (0.23+/-0.08 vs.
      0.24+/-0.07; P=ns). At baseline, (NT-)ANP and NT-proBNP levels were significantly
      higher in AF patients, compared with those in sinus rhythm. By multivariate
      regression analysis, AF was identified as independent determinant of (NT-)ANP,
      but not of (NT-pro)BNP levels. After a mean follow-up of 3.2+/-0.9 (range 0.4
      5.4) years, cardiovascular mortality was comparable (55 vs. 47%; P=ns). In both
      groups, AF and sinus rhythm, NT-proBNP [AF: adjusted HR 5.8 (1.3-25.4), P=0.02;
      sinus rhythm: adjusted HR 3.1 (1.7-5.7), P<0.001] was an independent risk
      indicator of cardiovascular mortality. CONCLUSION: In advanced CHF patients, AF
      affects (NT-)ANP levels, but not (NT-pro)BNP levels. NT-proBNP is an independent
      determinant of prognosis in advanced CHF, irrespective of the rhythm, AF, or
      sinus rhythm.

PMID- 16798761
TI  - Long term management of atrial arrhythmias in young patients with sick sinus
      syndrome undergoing early operation to correct congenital heart disease.
AB  - AIMS: The objective of our study was to evaluate the clinical outcome of patients
      with operated congenital heart disease (CHD), post-operative sinus node
      dysfunction and atrial tachyarrhythmias (AT) who had a new generation of DDDRP
      pacemakers (Model AT501, Medtronic Inc., MN, USA) able to deliver preventive
      atrial pacing and antitachycardia pacing (ATP) therapies. METHODS AND RESULTS:
      Fifteen CHD patients (mean age 17+/-9 years, eight after Mustard operation, five
      after extracardiac Fontan operation and two after atrial septum repair) received
      a dual-chamber pacemaker with transvenous (eight patients) or epicardial leads
      (seven patients). In the year before implantation, all patients had symptomatic
      AT (palpitations), eight patients required hospitalization and five required
      electrical cardioversion. Pacing prevention algorithms were enabled in all
      patients, and ATP therapies in six patients. During a mean follow-up of 30 months
      (range 24-44), three patients (two Fontan, one Mustard) died of CHF, whereas AT
      required hospitalization in three patients (two Fontan, one atrial septum
      repair). Only seven patients had symptomatic AT. One hundred and twenty-five AT
      episodes were treated by ATP in three patients, with an overall termination
      efficacy of 43.2%. In one patient, atrial lead noise induced inappropriate AT
      detection that resulted in ATP delivery. Several AT episodes were not treated
      owing to their very short duration, atrial undersensing, or 1:1 atrioventricular
      conduction. CONCLUSIONS: Our experience with antitachycardia pacemakers in CHD
      patients with post-operative sick sinus syndrome after biventricular correction
      or palliation shows that these devices are safe and that atrial pacing may play a
      role in AT prevention and treatment.

PMID- 16798762
TI  - Asymptomatic recurrences of atrial fibrillation after pulmonary vein isolation.
AB  - AIMS: The purpose of this study was to determine the occurrence of asymptomatic
      episodes of atrial fibrillation (AF) and wrong AF perception after pulmonary vein
      isolation (PVI). We evaluated the success of ablation by using the following
      measurements: (i) clinical symptoms and duration of symptoms noticed by patients
      and (ii) synchronous event recording (ER). METHODS AND RESULTS: Eighty patients
      with paroxysmal AF underwent PVI and were provided repeatedly with a portable ER
      upon discharge and every 3 months for a year. The ER automatically detects
      arrhythmias by a detection algorithm and can also be manually triggered by the
      patient. In 46/80 patients (57.5%), episodes of AF were documented. Asymptomatic
      AF was detected in 21.3%. In 9/80 patients (11.3%), who reported clinical AF
      recurrence, no AF could be shown by ER. We compared patients' perception to have
      suffered AF episodes with the ERs and found a sensitivity of 75% and a
      specificity of 92%. CONCLUSION: Reliance on perception of AF by patients after
      PVI results in an underestimation of recurrence of the arrhythmia. We observed a
      maximal occurrence of silent AF or wrong perception of AF in 26/80 (32.6%)
      patients.

PMID- 16798763
TI  - Cardiac resynchronization pacing without defibrillator capability: is this a
      viable option?
AB  - Improved cardiac resynchronization by pacemakers (CRT-P) and implantable
      defibrillators (CRT-D) benefits cardiac function, reduces heart failure (HF)
      admissions, and diminishes mortality in patients with severe left ventricular
      (LV) dysfunction. In terms of mortality benefit, current evidence suggests that
      CRT-D may be better than CRT-P alone when a broad range of HF patients is
      considered. However, the differential benefit may be small in certain patients.
      In individuals with severe and worsening HF due to systolic LV dysfunction, HF
      complications other than ventricular tachyarrhythmias contribute importantly to
      both quality-of-life (QoL) and duration of survival; these patients may be served
      cost-effectively by CRT-P enhancing QoL. A clinical trial evaluating CRT-D vs.
      CRT-P in terms of QoL and survival in such patients would assist physicians and
      payers to understand better the relative roles of CRT-P and CRT-D in the care of
      the sickest HF patients.

PMID- 16798764
TI  - Identification of lateral cardiac veins for cardiac resynchronization therapy.

PMID- 16798765
TI  - Heart rate turbulence and heart rate variability in patients with mitral valve
      prolapse.
AB  - AIMS: Heart rate turbulence (HRT) and heart rate variability (HRV) have been
      shown to be independent and powerful predictors of mortality in a specific group
      of cardiac patients. However, the predictive values of HRV alone is modest and
      information on HRV in patients with mitral valve prolapse (MVP) has so far been
      conflicting. In addition, no studies have previously evaluated HRT in patients
      with MVP. To define better the effects of MVP on cardiac autonomic function, we
      assessed HRT and time-domain parameters of HRV in patients with MVP. METHODS AND
      RESULTS: Fifty patients with MVP and 70 controls without MVP were investigated.
      The diagnosis of MVP was confirmed by cross-sectional echocardiography in the
      parasternal long-axis view and apical 4-chamber view. The HRV and turbulence
      analysis were assessed from a 24-hour Holter recording. When HRT parameters were
      compared, the values of the HRT onset and slope were significantly lower in MVP
      patients than in the controls group (-0.109+/-0.207 vs. -0.289+/-0.170%, P=0.001
      and 8.6+/-7.2 vs. 11.5+/-7.4 ms/RRI, P=0.043, respectively) and the number of
      patients who had abnormal HRT onset was significantly higher in the MVP group
      than in controls (15 vs. 8, P=0.011). In addition, HRV parameters were not
      statistically different between the two groups. CONCLUSION: Although we found
      that the decrease in HRV parameters was not significantly different between MVP
      patients and controls, HRT variables (especially HRT onset) were significantly
      lower in MVP patients. Therefore, in our opinion, HRT is an attractive, easily
      applicable, and better way of non-invasive risk prediction compared with another
      non-invasive risk predictor, HRV.

PMID- 16798766
TI  - Heart rate variability in an ageing population and its association with lifestyle
      and cardiovascular risk factors: results of the SAPALDIA study.
AB  - AIMS: (i) To report associations between cardiovascular risk factors and heart
      rate variability (HRV) in a general population and (ii) to provide normal values
      for various HRV measurements in a healthy European general population sample aged
      >or=50. METHODS AND RESULTS: Twenty-four-hour electrocardiograms were recorded in
      1742 randomly selected SAPALDIA (Swiss cohort study on Air Pollution and Lung
      Diseases in Adults) participants aged >or=50. In multivariate regression
      analyses, women (n=895) had a 6.1% lower standard deviation of all normal RR (NN)
      intervals (SDNN), a 11.4% lower total power (TP), and a 27.2% lower low-frequency
      (LF) power than men (n=847). Per unit increase in BMI, SDNN decreased by 0.7% and
      TP decreased by 1.2%. Persons with high blood pressure had a 9.2% lower LF than
      normotensive persons and current smokers a 15.5% lower LF than never smokers.
      Each hour of heavy physical exercise was associated with a 2.0% increase in SDNN,
      a 3.6% increase in the high frequency (HF) range power and a 4.2% increase in LF
      power. Higher levels of uric acid, high-sensitive C-reactive protein and non-HDL
      cholesterol were associated with lower TP, HF and LF. Percentiles of TP and LF/HF
      as a function of age were calculated for an asymptomatic subsample of
      participants (n=499) free of cardioactive medications. CONCLUSION: Heart rate
      variability in a general population sample shows expected associations with all
      known cardiovascular risk factors, although not identically for all HRV domains.
      Together with our percentile estimates for HRV as a function of age, these
      findings could assist scientists in interpreting 24 h HRV values and factors
      influencing them in an ageing population.

PMID- 16798767
TI  - Twenty years of paediatric cardiac pacing: 515 pacemakers and 480 leads implanted
      in 292 patients.
AB  - AIMS: The aim of this study was to evaluate long-term outcome of pacemakers (PMs)
      in paediatric patients. METHODS AND RESULTS: Patients' data were retrospectively
      reviewed. We recorded the techniques and systems used, any complication, and
      outcome. Endocardial leads were inserted by transcutaneous puncture of subclavian
      vein and fixed with a non-absorbable ligature, and epicardial leads by standard
      surgical technique. Lead survival was calculated and plotted with the product
      limit method of Kaplan-Meier. Between 1982 and 2002, 292 patients, aged 8+/-7
      years (range 1 day-18 years), underwent PM implantation: the first PM had
      endocardial leads in 165 patients and epicardial in 127 patients. Structural
      heart disease (HD) was present in 239 patients. Follow-up was 5+/-4 (range 0.1
      18) years. There were no pacing-related deaths. In total, 211 endocardial
      implantation procedures with 90 atrial and 165 ventricular leads and 145
      epicardial procedures with 103 atrial and 123 ventricular leads were performed.
      Early (<3 months) complications: haemothorax occurred in 3.5% of endocardial
      leads and dislodgement was not significantly different for atrial and ventricular
      endocardial leads. Late complications: 63 leads failed (48 epicardial), with the
      worst outcome for conventional epicardial leads (31 vs. 9% endocardial, P<0.05;
      steroid eluting 8% epicardial vs. 5% endocardial, P=NS). Endocardial atrial leads
      failed (7%) in operated HD and ventricular leads failed (6%) after body growth,
      without difference in estimated mean survival time (11 years). Early and late PM
      infection/erosion was approximately 2% in all patients. CONCLUSION: Pacing in
      children shows good results, but complications are frequent and related to leads.
      Endocardial pacing showed better long-term outcome.

PMID- 16798768
TI  - Determination of left ventricular volume changes by intracardiac conductance
      using a biventricular electrode configuration.
AB  - AIMS: The feasibility of determining left ventricular (LV) volume changes by LV
      conductance measurements with an implantable device was investigated in an animal
      model. METHODS AND RESULTS: The haemodynamic state of six mongrel dogs was
      altered by overpacing with rates up to 140 bpm and by isoprenaline infusion with
      dosages up to 0.2 microg/kg/min. The LV conductance, aortic blood flow, and LV
      and aortic pressure were recorded. Conductance measurements were carried out
      using the two electrodes of a bipolar right ventricular pacing lead for current
      injection and two epicardial leads screwed into the mid-lateral LV wall for
      measuring the resulting voltage. Stroke conductance (SY) was correlated with the
      LV stroke volume (LVSV), which was computed from the aortic flow. The LVSV rose
      to 188+/-14% with increasing isoprenaline dosage. A strong correlation between
      the LV conductance SY and the LVSV was found (mean r=0.97). The LVSV decreased to
      68+/-8% with an increasing pacing rate. Again, a strong correlation between SY
      and LVSV was found (mean r=0.89). CONCLUSION: This animal study confirms the
      feasibility of assessing changes in LVSV by determining the LV intracardiac
      conductance. This creates the possibility of continuous haemodynamic monitoring
      with implantable devices.

PMID- 16798769
TI  - Cardiac metastasis of malignant melanoma: a rare cause of complete
      atrioventricular block.
AB  - Malignant melanoma has an aggressive biological behaviour and a high rate of
      cardiac involvement. As shown from post-mortem studies, metastases of melanoma
      can involve any organ and cardiac metastases are frequent. This report describes
      a case of widespread malignant melanoma in a patient with clinical presentation
      of complete atrioventricular (AV) block. Thorax CT and transthoracic
      echocardiography revealed a mass involving the conduction system. By VDD
      permanent pacing (atrial synchronous ventricular pacing), haemodynamic stability
      was maintained and the patient remains under follow-up receiving chemo
      immunotherapy. In the retrospective analysis of the patient's records, we
      realized that the AV conduction delay had been progressing for at least 7 months.
      Cardiac metastasis of malignant melanoma is a common finding and can proceed in
      the absence of overt clinical manifestations. Therefore, the clinician should be
      alert to the development of cardiac signs and symptoms in a metastatic melanoma
      patient and should perform a detailed cardiac examination to exclude cardiac
      metastasis of the tumour.

PMID- 16798770
TI  - Electrophysiological and antiarrhythmic effects of the novel antiarrhythmic agent
      AZD7009: a comparison with azimilide and AVE0118 in the acutely dilated right
      atrium of the rabbit in vitro.
AB  - AIMS: To compare the electrophysiological and antiarrhythmic effects of AZD7009,
      azimilide, and AVE0118 in the acutely dilated rabbit atria in vitro. METHODS AND
      RESULTS: In the isolated Langendorf-perfused rabbit heart, the atrial effective
      refractory period (AERP) and the inducibility of atrial fibrillation (AF) were
      measured at increasing concentrations of AZD7009 (0.1-3 microM), azimilide (0.1-3
      microM), and AVE0118 (0.3-10 microM). In separate groups of atria, termination of
      sustained AF was assessed. In non-dilated atria, the AERP was 82+/-1.3 ms (mean+/
      SEM) and AF could not be induced. Dilation significantly reduced the AERP to 49+/
      1.0 ms (P<0.001) and 92% of the atria became inducible. Perfusion with AZD7009,
      azimilide, and AVE0118 concentration-dependently increased the AERP and reduced
      the AF inducibility. At the highest concentrations of AZD7009, azimilide, and
      AVE0118, AERP and AF inducibility changed from 50+/-4.5 to 136+/-6.6 ms and 80 to
      0% (both P<0.001) from 51+/-3.0 to 105+/-9.9 ms (P<0.001) and 80 to 0% (P<0.01)
      and from 46+/-2.8 to 85+/-6.0 ms and 90 to 0% (both P<0.001). Restoration of
      sinus rhythm was seen in 6/6, 5/6, and 5/6 hearts perfused with AZD7009,
      azimilide, and AVE0118, respectively. CONCLUSION: In the dilated rabbit atria,
      AZD7009, azimilide, and AVE0118 concentration-dependently increased AERP,
      effectively prevented AF induction, and rapidly restored sinus rhythm.

PMID- 16798771
TI  - Anaesthetic management for hip arthroplasty in a 46-yr-old patient with
      uncorrected truncus arteriosus type IV.
AB  - In modern adult anaesthetic practice uncorrected complex congenital heart lesions
      are rare. Persistent truncus arteriosus accounts for only 1.2-3% of all
      congenital heart malformations. If not corrected, fewer than 20% of these
      patients survive the first year of life. Here we report the successful management
      of an adult patient with uncorrected truncus arteriosus who presented for hip
      arthroplasty.

PMID- 16798772
TI  - Continuous spinal microcatheter (28 gauge) technique for arterial bypass surgery
      of the lower extremities and comparison of ropivacaine with or without morphine
      for postoperative analgesia.
AB  - BACKGROUND: The aim of this study was to evaluate a microcatheter technique for
      continuous spinal anaesthesia (CSA) and continuous spinal postoperative analgesia
      (CSPA) in vascular surgery. METHODS: A total of 47 patients (range 51-95 yr, ASA
      II-IV) undergoing peripheral bypass surgery of the lower extremities received a
      spinal microcatheter (28 gauge) at L3-L4 or L2-L3. For CSA, ropivacaine 7.5 mg
      ml(-1) was given in small increments. Central venous pressure was maintained
      >or=3 mm Hg. Of 47 patients, 44 received CSPA, either using ropivacaine alone 2
      mg h(-1) (group R, n=22) or ropivacaine 1 mg h(-1) with morphine 8 microg h(-1)
      (group RM, n=22) for 24 h after surgery (randomized, double-blinded). RESULTS:
      Intraoperative haemodynamic control was good; during the initial 60 min only four
      patients received phenylephrine i.v. for hypotension. Up to 30% of the patients
      felt mild pain at incision but surgery [mean duration 173 min (range 66-327)] was
      successfully completed under CSA in 45 patients. In four instances of acute
      revision surgery, a new block was administered utilizing the spinal catheter in
      place. Postoperative pain relief was comparably adequate in both groups with no
      difference in rescue pain medication. Four patients (three in R, one in RM) had
      weak motor blockade in the first postoperative morning. CONCLUSIONS: The
      described CSA technique offered good haemodynamic control, ease of maintaining
      spinal anaesthesia, and ease of providing a new spinal block for revision. The
      combination of low-dose ropivacaine and morphine for CSPA did not offer any
      benefit compared with the higher ropivacaine dose alone.

PMID- 16798773
TI  - Efficacy of three doses of tramadol with bupivacaine for caudal analgesia in
      paediatric inguinal herniotomy.
AB  - BACKGROUND: This study was designed to evaluate the analgesic efficacy of three
      doses of tramadol, administered caudally with bupivacaine, in providing
      postoperative pain relief in children. METHODS: Eighty children, aged between 2
      and 8 yr, undergoing inguinal herniotomy were randomly allocated to receive
      bupivacaine 0.25% 0.75 ml kg(-1) (Group B; n=20), bupivacaine 0.25% 0.75 ml kg(
      1) with tramadol 1 mg kg(-1) (Group BT1; n=20), bupivacaine 0.25% 0.75 ml kg(-1)
      with tramadol 1.5 mg kg(-1) (Group BT1.5; n=20), or bupivacaine 0.25% 0.75 ml kg(
      1) with tramadol 2 mg kg(-1) (Group BT2; n=20) by the caudal route immediately
      after induction of general anaesthesia. Heart rate, arterial pressure and oxygen
      saturation were monitored. Postoperative pain was assessed at regular intervals
      for 24 h using All India Institute of Medical Sciences pain score. Analgesia was
      supplemented whenever pain score was >or=4. Duration of analgesia and requirement
      for additional analgesics was noted. RESULTS: Duration of analgesia was longer in
      Group BT2 [(mean (SD) 12 (0.9) h] compared with Group B [4 (1) h], Group BT1 [8
      (0.9) h], or Group BT1.5 [11 (1) h]; all P<0.001. Total consumption of rescue
      analgesic was significantly lower in group BT2 compared with other groups
      (P<0.001). There were no significant changes in heart rate, arterial pressure and
      oxygen saturation between groups. Adverse effects were not observed. CONCLUSIONS:
      Caudal tramadol 2 mg kg(-1), combined with bupivacaine 0.25% 0.75 ml kg(-1),
      provided longer duration of postoperative analgesia and reduced requirement for
      rescue analgesic compared with tramadol 1 mg kg(-1) or 1.5 mg kg(-1) in children
      undergoing inguinal herniotomy.

PMID- 16798774
TI  - Ultrasonography-guided rectus sheath block in paediatric anaesthesia--a new
      approach to an old technique.
AB  - BACKGROUND: The purpose of this study was an anatomical and clinical evaluation
      of ultrasonography-guided rectus sheath blocks in children. METHOD: A total of 30
      children were included in the sono-anatomical part of the study. The depth of the
      anterior and posterior rectus sheath was evaluated with a portable SonSite 180
      plus ultrasound machine and a 5-10 MHz linear probe. In total, 20 consecutive
      children undergoing umbilical hernia repair were included in the clinical part of
      this study. After induction of general anaesthesia children received a rectus
      sheath block under real-time ultrasonographic guidance by placing 0.1 ml kg(-1)
      bilaterally in the space between the posterior aspect of the sheath and the
      rectus abdominis muscle. RESULTS: Ultrasonographic visualization of the posterior
      rectus sheath was possible in all children. The correlation between the depth of
      the posterior rectus sheath and weight (adjusted r(2)=0.175), height (adjusted
      r(2)=0.314) and body surface area (adjusted r(2)=0.241) was poor. The ultrasound
      guided rectus sheath blockade provided sufficient analgesia in all children with
      no need for additional analgesia in the perioperative period. CONCLUSION: The
      bilateral placement of levobupivacaine 0.25% 0.1 ml kg(-1) in the space between
      the posterior aspect of the rectus sheath and the rectus abdominis muscle under
      real-time ultrasonographic guidance provides sufficient analgesia for umbilical
      hernia repair. The unpredictable depth of the posterior rectus sheath in children
      is a good argument for the use of ultrasonography in this regional anaesthetic
      technique in children.

PMID- 16798776
TI  - Activation of 4-alpha-glucanotransferase activity of porcine liver glycogen
      debranching enzyme with cyclodextrins.
AB  - Glycogen debranching enzyme (GDE) is a single polypeptide chain containing
      distinct active sites for 4-alpha-glucanotransferase and amylo-alpha-1,6
      glucosidase activities. Debranching of phosphorylase limit dextrin from glycogen
      is carried out by cooperation of the two activities. We examined the effects of
      cyclodextrins (CDs) on debranching activity of porcine liver GDE using a
      fluorogenic branched dextrin, Glcalpha1-4Glcalpha1-4Glcalpha1-4(Glcalpha1
      4Glcalpha1-4Glcalpha1-4Glcalpha1-6)Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1
      4GlcPA (B5/84), as a substrate. B5/84 was hydrolyzed by the hydrolytic action of
      4-alpha-glucanotransferase to B5/81 and maltotriose. The fluorogenic product was
      further hydrolyzed by the amylo-alpha-1,6-glucosidase activity to the debranched
      product, Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1-4Glcalpha1
      4Glcalpha1-4GlcPA (G8PA), and glucose. alpha-, beta- and gamma-CDs accelerated
      the liberation of B5/81 from B5/84, indicating that the 4-alpha
      glucanotransferase activity was activated by CDs to remove the maltotriosyl
      residue from the maltotetraosyl branch. This led to acceleration of B5/84
      debranching. The extent of 4-alpha-glucanotransferase activation increased with
      CD concentration before reaching a constant value. This suggests that there is an
      activator binding site and that the binding of CDs stimulates 4-alpha
      glucanotransferase activity. In the porcine liver, glycogen degradation may be
      partially stimulated by the binding of a glycogen branch to this activator
      binding site.

PMID- 16798775
TI  - Accumulation of FFA-1, the Xenopus homolog of Werner helicase, and DNA polymerase
      delta on chromatin in response to replication fork arrest.
AB  - Werner syndrome is a genetic disorder characterized by premature aging and cancer
      prone symptoms, and is caused by mutation of the WRN gene. WRN is a member of the
      RecQ helicase family and is thought to function in processes implicated in DNA
      replication and repair to maintain genome stability; however, its precise
      function is still unclear. We found that replication fork arrest markedly
      enhances chromatin binding of focus-forming activity 1 (FFA-1), a Xenopus WRN
      homolog, in Xenopus egg extracts. In addition to FFA-1, DNA polymerase delta
      (Poldelta) and replication protein A, but not DNA polymerase epsilon and
      proliferating cell nuclear antigen, accumulated increasingly on replication
      arrested chromatin. Elevated accumulation of these proteins was dependent on
      formation of pre-replicative complexes (pre-RCs). Double-strand break (DSB)
      formation also enhanced chromatin binding of FFA-1, but not Poldelta,
      independently of pre-RC formation. In contrast to FFA-1, chromatin binding of
      Xenopus Bloom syndrome helicase (xBLM) only slightly increased after replication
      arrest or DSB formation. Thus, WRN-specific, distinct processes can be reproduced
      in the in vitro system in egg extracts, and this system is useful for biochemical
      analysis of WRN functions during DNA metabolism.

PMID- 16798777
TI  - The relationship between intramembranous particles and aquaporin molecules in the
      plasma membranes of normal rat skeletal muscles: a fracture-label study.
AB  - The plasma membrane of skeletal muscles contains water channels such as aquaporin
      4 (AQP4), aquaporin 3 (AQP3) and aquaporin 7 (AQP7). In dehydrated mice, we have
      recently reported the altered distribution of the aggregations of intramembranous
      particles (IMPs), such as orthogonal array (a crystal-like structure) and IMP
      cluster (a rosette-like structure) on the freeze-fractured skeletal muscle plasma
      membranes. In this fracture-label study, we first tested whether the orthogonal
      arrays (OAs) were composed of AQP4 in skeletal muscles and further analyzed the
      relationship between IMPs including IMP clusters and AQP3 molecules. As a result,
      many of the gold particles indicating AQP4 was associated with OAs (79%) by our
      fracture-label technique. On the other hand, approximately 50% of gold particles
      indicating AQP3 were associated with IMP clusters. Thus we confirmed that the OAs
      are composed of AQP4 in skeletal muscles, and further demonstrated that some of
      the IMP clusters are composed of AQP3 and may participate in maintaining osmotic
      homeostasis in skeletal myofibers. The fracture-label method is useful in
      investigating the molecular identification of membrane proteins such as AQP3 and
      AQP4.

PMID- 16798778
TI  - High incidence of allograft dysfunction in liver transplanted patients treated
      with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence:
      possible de novo autoimmune hepatitis?
AB  - BACKGROUND: Interferon may trigger autoimmune disorders, including autoimmune
      hepatitis, in immunocompetent patients. To date, no such disorders have been
      described in liver transplanted patients. METHODS: 9 of 44 liver transplanted
      patients who had been receiving pegylated-interferon alpha-2b and ribavirin for
      at least 6 months for hepatitis C virus (HCV) recurrence, developed graft
      dysfunction despite on-treatment HCV-RNA clearance in all but one case.
      Laboratory, microbiological, imaging and histological evaluations were performed
      to identify the origin of graft dysfunction. The International Autoimmune
      Hepatitis scoring system was also applied. RESULTS: In all cases infections,
      anastomoses complications and rejection were excluded, whereas the autoimmune
      hepatitis score suggested a "probable autoimmune hepatitis" (score from 10 to
      14). Three patients developed other definite autoimmune disorders (overlap anti
      mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and
      systemic lupus erythematosus, respectively). In all cases, pre-existing
      autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in
      immunosuppressive induction treatment correlated with the development of the
      disorder, whereas the use of granulocyte colony-stimulating factor to treat
      interferon-induced neutropenia showed a protective role. Withdrawal of antiviral
      treatment and treatment with prednisone resulted in different outcomes (five
      remissions and four graft failures with two deaths). CONCLUSIONS: De novo
      autoimmune hepatitis should be considered in differential diagnosis along with
      rejection in liver transplanted patients developing graft dysfunction while on
      treatment with interferon.

PMID- 16798779
TI  - Gene expression profiling identifies regulatory pathways involved in the late
      stage of rat fetal lung development.
AB  - Fetal lung development is a complex biological process that involves temporal and
      spatial regulations of many genes. To understand the molecular mechanisms of this
      process, we investigated gene expression profiles of fetal lungs on gestational
      days 18, 19, 20, and 21, as well as newborn and adult rat lungs. For this
      analysis, we used an in-house rat DNA microarray containing 6,000 known genes and
      4,000 expressed sequence tags (ESTs). Of these, 1,512 genes passed the
      statistical significance analysis of microarray (SAM) test; an at least twofold
      change was shown for 583 genes (402 known genes and 181 ESTs) between at least
      two time points. K-means cluster analysis revealed seven major expression
      patterns. In one of the clusters, gene expression increased from day 18 to day 20
      and then decreased. In this cluster, which contained 10 known genes and 5 ESTs, 8
      genes are associated with development. These genes can be integrated into
      regulatory pathways, including growth factors, plasma membrane receptors,
      adhesion molecules, intracellular signaling molecules, and transcription factors.
      Real-time PCR analysis of these 10 genes showed an 88% consistency with the
      microarray data. The mRNA of LIM homeodomain protein 3a (Lhx3), a transcription
      factor, was enriched in fetal type II cells. In contrast, pleiotrophin, a growth
      factor, had a much higher expression in fetal lung tissues than in fetal type II
      cells. Immunohistochemistry revealed that Lhx3 was localized in fetal lung
      epithelial cells and pleiotrophin in the mesenchymal cells adjacent to the
      developing epithelium and blood vessel. Using GenMAPP, we identified four
      regulatory pathways: transforming growth factor-beta signaling, inflammatory
      response, cell cycle, and G protein signaling. We also identified two metabolic
      pathways: glycolysis-gluconeogenesis and proteasome degradation. Our results may
      provide new insights into the complex regulatory pathways that control fetal lung
      development.

PMID- 16798780
TI  - Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in
      lung epithelial cells.
AB  - Aldolase C (EC 4.1.2.13) is a brain-specific aldolase isoform and a putative
      target of the transcription factor hypoxia-inducible factor (HIF)-1. We
      identified aldolase C as a candidate hypoxia-regulated gene in mouse lung
      epithelial (MLE) cells using differential display. We show that the message
      accumulates in a robust fashion when MLE cells are exposed to 1% oxygen and is
      inversely related to oxygen content. Induction in hypoxia is dependent on protein
      synthesis. We localized a hypoxia-responsive element (HRE) in the aldolase C
      promoter using a series of deletion and heterologous expression studies. The HRE
      overlaps with a region of the proximal aldolase C promoter that is also related
      to its brain-specific expression. The HRE contains an Arnt (HIF-1beta) and an HIF
      1alpha site. We show that induction in hypoxia is dependent on the HIF-1 site and
      that HIF-1alpha protein is present, by gel-shift assay, within nuclear complexes
      of MLE cells in hypoxia. Aldolase C mRNA expression is developmentally regulated
      in the fetal lung, rapidly downregulated in the newborn lung at birth, and
      inducible in the adult lung when exposed to hypoxia. This pattern of regulation
      is not seen in the brain. This preservation of this HRE in the promoters of four
      other species suggests that aldolase C may function as a stress-response gene.

PMID- 16798781
TI  - Role of substance P in hydrogen sulfide-induced pulmonary inflammation in mice.
AB  - We have shown earlier that H(2)S acts as a mediator of inflammation. In this
      study, we have investigated the involvement of substance P and neurogenic
      inflammation in H(2)S-induced lung inflammation. Intraperitoneal administration
      of NaHS (1-10 mg/kg), an H(2)S donor, to mice caused a significant increase in
      circulating levels of substance P in a dose-dependent manner. H(2)S alone could
      also cause lung inflammation, as evidenced by a significant increase in lung
      myeloperoxidase activity and histological evidence of lung injury. The maximum
      effect of H(2)S on substance P levels and on lung inflammation was observed 1 h
      after NaHS administration. At this time, a significant increase in lung levels of
      TNF-alpha and IL-1beta was also observed. In substance P-deficient mice, the
      preprotachykinin-A knockout mice, H(2)S did not cause any lung inflammation.
      Furthermore, pretreatment of mice with CP-96345 (2.5 mg/kg ip), an antagonist of
      the neurokinin-1 (NK(1)) receptor, protected mice against lung inflammation
      caused by H(2)S. However, treatment with antagonists of NK(2), NK(3), and CGRP
      receptors did not have any effect on H(2)S-induced lung inflammation. Depleting
      neuropeptide from sensory neurons by capsaicin (50 mg/kg sc) significantly
      reduced the lung inflammation caused by H(2)S. In addition, pretreatment of mice
      with capsazepine (15 mg/kg sc), an antagonist of the transient receptor potential
      vanilloid-1, protected mice against H(2)S-induced lung inflammation. These
      results demonstrate a key role of substance P and neurogenic inflammation in
      H(2)S-induced lung injury in mice.

PMID- 16798782
TI  - Life-years-gained from population risk factor changes and modern cardiology
      treatments in Ireland.
AB  - BACKGROUND: Coronary heart disease (CHD) mortality rates in Ireland have halved
      since the mid-1980s, and adult life expectancy has also steadily improved. This
      study estimated the life-years-gained by CHD treatments and by changes in
      cardiovascular risk factor levels. METHODS: A previously validated Irish IMPACT
      CHD mortality model was used to integrate large amounts of data on (i) patient
      numbers, (ii) treatment uptake, (iii) risk factor trends, (iv) effectiveness of
      cardiology treatments and risk factor reductions, and (v) median survival in
      patients with and without CHD, all stratified by age and sex. Results were tested
      in rigorous sensitivity analyses. RESULTS: There were 3763 fewer CHD deaths than
      expected in 2000 compared with the base year, 1985. This resulted in
      approximately 44,060 life-years-gained among people aged 25-84. Specific medical
      and surgical treatments given in 2000 for CHD patients together gained
      approximately 14,505 life-years. Population changes in cholesterol and smoking
      levels accounted for some 32,705 life-years-gained, 66% from reductions in
      cholesterol alone. Adverse changes in obesity and diabetes resulted in a loss of
      approximately 3670 life-years. CONCLUSIONS: Use of modern cardiology treatments
      in Ireland from 1985 to 2000 gained many thousands of life-years. However, twice
      as many life-years were generated by relatively modest reductions in major risk
      factors. Effective policies, such as the promotion of healthy diets, and weight
      reduction, together with the recent nationwide workplace smoking ban, will be
      essential to maintain and further enhance health gain.

PMID- 16798783
TI  - The limitations on choice: Palestinian women's childbirth location,
      dissatisfaction with the place of birth and determinants.
AB  - BACKGROUND: Analysing the Palestinian Central Bureau of Statistics (PCBS)
      Demographic and Health Survey 2004 (DHS-2004) data, this article focuses on the
      question of where women living in the Occupied Palestinian Territory give birth,
      and whether it was the preferred/place of choice for delivery. We further
      identify some of the determinants of women's dissatisfaction with childbirth
      location. METHODS: A total of 2158 women residing in the West Bank and Gaza Strip
      were included in this study. Regression analysis established the association
      between dissatisfaction with the place of birth and selected determinants.
      RESULTS: A total of 3.5% of women delivered at home, with the rest in assisted
      facilities. Overall, 20.5% of women reported that their childbirth location was
      not the preferred place of delivery. Women who delivered at home; in governmental
      facilities; in regions other than the central West Bank; who had sudden delivery
      or did not reach their preferred childbirth location because of closures and
      siege; because of costs/the availability of insurance; or because there were no
      other locations available, were significantly more likely to be dissatisfied with
      their childbirth location compared to those who birthed in private facilities,
      the central West Bank, and in locations with better and more available services.
      CONCLUSION: The findings demonstrate that Palestinian women's choice of a place
      of birth is constrained and modified by the availability, affordability, and
      limited access to services induced by continuing closures and siege. These
      findings need to be taken into consideration when planning for maternity services
      in the Occupied Palestinian Territory.

PMID- 16798784
TI  - Live viral vaccines in a DiGeorge syndrome patient.
AB  - We report a case of pneumonia in a 13 month old male child with partial DiGeorge
      syndrome who died after inadvertently receiving live viral vaccines. Although
      live viral vaccines have been used safely in some children with DiGeorge
      syndrome, there are insufficient data to recommend their routine use in those
      with severe immunodeficiency.

PMID- 16798785
TI  - Tacrolimus ointment does not affect the immediate response to vaccination, the
      generation of immune memory, or humoral and cell-mediated immunity in children.
AB  - BACKGROUND: Concern exists that the prolonged application of immunomodulators to
      treat atopic dermatitis may cause systemic immunosuppression. AIMS: In a 7-month,
      multicentre, randomised, controlled trial, we investigated the equivalence of
      response to vaccination against meningococcal serogroup C disease with a protein
      conjugate vaccine in children (2-11 years) with moderate to severe atopic
      dermatitis, by applying either 0.03% tacrolimus ointment (TAC-O; n =
      121[corrected]) or a hydrocortisone ointment regimen (HC-O; n = 111). METHODS:
      TAC-O was applied twice daily (bid) for 3 weeks, and thereafter daily until
      clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone
      butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was
      applied bid to all affected areas. At week 1, patients were vaccinated with
      protein-conjugate vaccine against meningococcal serogroup C, and challenged at
      month 6 with low dose meningococcal polysaccharide vaccine. The control group (44
      non-atopic dermatitis children) received the primary vaccination and challenge
      dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The
      primary end point was the percentage of patients with a serum bactericidal
      antibody (SBA) titre > or = 8 at the week 5 visit. RESULTS: The response rate
      (patients with SBA titre > or = 8) was 97.5% (confidence interval (CI)
      approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the
      TAC-O, HC-O and control groups, respectively. CONCLUSIONS: The immune response to
      vaccination against meningococcal serogroup C in children with atopic dermatitis
      applying either 0.03% TAC-O or HC is equivalent. Ointment application does not
      affect the immediate response to vaccination, generation of immune memory or
      humoral and cell-mediated immunity.

PMID- 16798786
TI  - Does patent ductus arteriosus affect feed tolerance in preterm neonates?
AB  - Patent ductus arteriosus (PDA), especially PDA with sepsis, has been reported as
      a risk factor for feed intolerance in preterm neonates. In this study, the start
      to full feeds interval was found to be longest in preterm neonates (<or=28 weeks'
      gestation) with sepsis, followed by that in preterm neonates with sepsis and PDA,
      and in those with PDA alone.

PMID- 16798787
TI  - Non-invasive measurement of reduced ventilation:perfusion ratio and shunt in
      infants with bronchopulmonary dysplasia: a physiological definition of the
      disease.
AB  - BACKGROUND: An objective definition of bronchopulmonary dysplasia (BPD) is
      required to interpret trial outcomes and provide a baseline for prognostic
      studies. Current definitions do not quantify disease severity. The cardinal
      measures of impaired gas exchange are a reduced ventilation:perfusion ratio
      (V(A):Q) and increased right to left shunt. These can be determined non
      invasively by plotting arterial oxygen saturation (Spo(2)) against inspired
      oxygen pressure (PIo(2)). AIMS: To describe the reduced V(A):Q and shunt in
      infants with BPD and evaluate these as graded measures of pulmonary dysfunction.
      METHODS: 21 preterm infants with BPD were studied. PIo(2) was changed stepwise to
      vary Spo(2) between 86% and 94%. Pairs of PIo(2) and Spo(2) data points for each
      infant were plotted and analysed to derive reduced V(A):Q ratio and shunt.
      RESULTS: In every infant, the Spo(2) versus PIo(2) curve was shifted to the right
      of the normal because of a reduced V(A):Q. The mean (SD) shift was 16.5 (4.7) kPa
      (normal 6 kPa). Varying degrees of shunt were also present, but these were less
      important in determining Spo(2) within the studied range. The degree of shift was
      strongly predictive of the PIo(2) required to achieve any Spo(2) within the range
      86-94% (R(2)>0.9), permitting shift and V(A):Q to be determined from a single
      pair of PIo(2) and SpO(2) values in this range. CONCLUSIONS: The predominant gas
      exchange impairment in BPD is a reduced V(A):Q, described by the right shift of
      the Spo(2) versus PIo(2) relationship. This provides a simpler method for
      defining BPD, which can grade disease severity.

PMID- 16798792
TI  - Pragmatic randomized trial evaluating the clinical and economic effectiveness of
      acupuncture for chronic low back pain.
AB  - In a randomized controlled trial plus a nonrandomized cohort, the authors
      investigated the effectiveness and costs of acupuncture in addition to routine
      care in the treatment of chronic low back pain and assessed whether the effects
      of acupuncture differed in randomized and nonrandomized patients. In 2001, German
      patients with chronic low back pain were allocated to an acupuncture group or a
      no-acupuncture control group. Persons who did not consent to randomization were
      included in a nonrandomized acupuncture group. All patients were allowed to
      receive routine medical care in addition to study treatment. Back function
      (Hannover Functional Ability Questionnaire), pain, and quality of life were
      assessed at baseline and after 3 and 6 months, and cost-effectiveness was
      analyzed. Of 11,630 patients (mean age=52.9 years (standard deviation, 13.7); 59%
      female), 1,549 were randomized to the acupuncture group and 1,544 to the control
      group; 8,537 were included in the nonrandomized acupuncture group. At 3 months,
      back function improved by 12.1 (standard error (SE), 0.4) to 74.5 (SE, 0.4)
      points in the acupuncture group and by 2.7 (SE, 0.4) to 65.1 (SE, 0.4) points
      among controls (difference=9.4 points (95% confidence interval 8.3, 10.5);
      p<0.001). Nonrandomized patients had more severe symptoms at baseline and showed
      improvements in back function similar to those seen in randomized patients. The
      incremental cost-effectiveness ratio was euro10,526 (euros) per quality-adjusted
      life year. Acupuncture plus routine care was associated with marked clinical
      improvements in these patients and was relatively cost-effective.

PMID- 16798794
TI  - Chronic kidney disease in adults--UK guidelines for identification, management
      and referral.

PMID- 16798793
TI  - Ambient air pollution and asthma exacerbations in children: an eight-city
      analysis.
AB  - The authors investigated the relation between ambient concentrations of five of
      the Environmental Protection Agency's criteria pollutants and asthma
      exacerbations (daily symptoms and use of rescue inhalers) among 990 children in
      eight North American cities during the 22-month prerandomization phase (November
      1993-September 1995) of the Childhood Asthma Management Program. Short-term
      effects of carbon monoxide, nitrogen dioxide, particulate matter less than 10 mum
      in aerodynamic diameter (PM10), sulfur dioxide, and warm-season ozone were
      examined in both one-pollutant and two-pollutant models, using lags of up to 2
      days. Lags in carbon monoxide and nitrogen dioxide were positively associated
      with both measures of asthma exacerbation, and the 3-day moving sum of sulfur
      dioxide levels was marginally related to asthma symptoms. PM10 and ozone were
      unrelated to exacerbations. The strongest effects tended to be seen with 2-day
      lags, where a 1-parts-per-million change in carbon monoxide and a 20-parts-per
      billion change in nitrogen dioxide were associated with symptom odds ratios of
      1.08 (95% confidence interval (CI): 1.02, 1.15) and 1.09 (95% CI: 1.03, 1.15),
      respectively, and with rate ratios for rescue inhaler use of 1.06 (95% CI: 1.01,
      1.10) and 1.05 (95% CI: 1.01, 1.09), respectively. The authors believe that the
      observed carbon monoxide and nitrogen dioxide associations can probably be
      attributed to mobile-source emissions, though more research is required.

PMID- 16798795
TI  - Reconstructing the evolutionary history of polyploids from multilabeled trees.
AB  - In recent studies, phylogenetic networks have been derived from so-called
      multilabeled trees in order to understand the origins of certain polyploids.
      Although the trees used in these studies were constructed using sophisticated
      techniques in phylogenetic analysis, the presented networks were inferred using
      ad hoc arguments that cannot be easily extended to larger, more complicated
      examples. In this paper, we present a general method for constructing such
      networks, which takes as input a multilabeled phylogenetic tree and outputs a
      phylogenetic network with certain desirable properties. To illustrate the
      applicability of our method, we discuss its use in reconstructing the
      evolutionary history of plant allopolyploids. We conclude with a discussion
      concerning possible future directions. The network construction method has been
      implemented and is freely available for use from http://www.uea.ac.uk/
      approximately a043878/padre.html.

PMID- 16798796
TI  - CW-EPR and ENDOR study of cytochrome c6 from Anabaena PCC 7119.
AB  - The detailed analysis of the continuous-wave electron paramagnetic resonance and
      electron nuclear double resonance measurements on cytochrome c(6) from Anabaena
      PCC7119 reveals several electronic and structural properties of this hemeprotein.
      The oxidized protein shows two forms that differ in the arrangement of the
      residues that act as heme axial ligands. Information about the orientation of
      these residues is obtained for one of the forms, which turns out to differ from
      that found in the reduced protein from x-ray experiments. The biological
      significance of these results is discussed.

PMID- 16798797
TI  - Positive inotropic effects of low dATP/ATP ratios on mechanics and kinetics of
      porcine cardiac muscle.
AB  - Substitution of 2'-deoxy ATP (dATP) for ATP as substrate for actomyosin results
      in significant enhancement of in vitro parameters of cardiac contraction. To
      determine the minimal ratio of dATP/ATP (constant total NTP) that significantly
      enhances cardiac contractility and obtain greater understanding of how dATP
      substitution results in contractile enhancement, we varied dATP/ATP ratio in
      porcine cardiac muscle preparations. At maximum Ca(2+) (pCa 4.5), isometric force
      increased linearly with dATP/ATP ratio, but at submaximal Ca(2+) (pCa 5.5) this
      relationship was nonlinear, with the nonlinearity evident at 2-20% dATP; force
      increased significantly with only 10% of substrate as dATP. The rate of tension
      redevelopment (k(TR)) increased with dATP at all Ca(2+) levels. k(TR) increased
      linearly with dATP/ATP ratio at pCa 4.5 and 5.5. Unregulated actin-activated Mg
      NTPase rates and actin sliding speed linearly increased with the dATP/ATP ratio
      (p < 0.01 at 10% dATP). Together these data suggest cardiac contractility is
      enhanced when only 10% of the contractile substrate is dATP. Our results imply
      that relatively small (but supraphysiological) levels of dATP increase the number
      of strongly attached, force-producing actomyosin cross-bridges, resulting in an
      increase in overall contractility through both thin filament activation and
      kinetic shortening of the actomyosin cross-bridge cycle.

PMID- 16798798
TI  - Structural change in lipid bilayers and water penetration induced by shock waves:
      molecular dynamics simulations.
AB  - The structural change of a phospholipid bilayer in water under the action of a
      shock wave is numerically studied with unsteady nonequilibrium molecular dynamics
      simulations. The action of shock waves is modeled by the momentum change of water
      molecules, and thereby we demonstrate that the resulting collapse and rebound of
      the bilayer are followed by the penetration of water molecules into the
      hydrophobic region of the bilayer. The high-speed phenomenon that occurs during
      the collapse and rebound of the bilayer is analyzed in detail, particularly
      focusing on the change of bilayer thickness, the acyl chain bend angles, the
      lateral fluidity of lipid molecules, and the penetration rate of water molecules.
      The result shows that the high-speed phenomenon can be divided into two stages:
      in the first stage the thickness of bilayer and the order parameter are rapidly
      reduced, and then in the second stage they are recovered relatively slowly. It is
      in the second stage that water molecules are steadily introduced into the
      hydrophobic region. The penetration of water molecules is enhanced by the shock
      wave impulse and this qualitatively agrees with a recent experimental result.

PMID- 16798799
TI  - A model for the circadian rhythm of cyanobacteria that maintains oscillation
      without gene expression.
AB  - An intriguing property of the cyanobacterial circadian clock is that endogenous
      rhythm persists when protein abundances are kept constant either in the presence
      of translation and transcription inhibitors or in the constant dark condition.
      Here we propose a regulatory mechanism of KaiC phosphorylation for the generation
      of circadian oscillations in cyanobacteria. In the model, clock proteins KaiA and
      KaiB are assumed to have multiple states, regulating the KaiC phosphorylation
      process. The model can explain 1), the sustained oscillation of gene expression
      and protein abundance when the expression of the kaiBC gene is regulated by KaiC
      protein, and 2), the sustained oscillation of phosphorylated KaiC when
      transcription and translation processes are inhibited and total protein abundance
      is fixed. Results of this work suggest that KaiA and KaiB strengthen the
      nonlinearity of KaiC phosphorylation, thereby promoting the circadian rhythm in
      cyanobacteria.

PMID- 16798800
TI  - An optimal number of molecules for signal amplification and discrimination in a
      chemical cascade.
AB  - Understanding the information processing ability of signal transduction pathways
      is of great importance because of their crucial roles in triggering various
      cellular responses. Despite continuing theoretical investigation, some important
      aspects of signal transduction such as a transient response and its connection to
      stochasticity originating from a small number of molecules have not yet been well
      understood. It is, however, through these aspects that unexpected and nontrivial
      properties of the information processing emerge. In this article, we analyze the
      transient behavior of a simple signaling cascade by taking into account the
      stochasticity originating from the small number of molecules. We identify several
      properties of the signaling cascade that emerge as a result of the interplay
      between the stochasticity and transient dynamics of the cascade. We specifically
      demonstrate that each step of the cascade has an optimal number of signaling
      molecules at which the average signal amplitude becomes maximal. We further
      investigate the connection between a finite number of molecules and the ability
      of the cascade to discriminate between true and error signals, which cannot be
      inferred from deterministic descriptions. The implications of our results are
      discussed from both biological and mathematical viewpoints.

PMID- 16798801
TI  - Structural determinants for the differences in voltage gating of chicken Cx56 and
      Cx45.6 gap-junctional hemichannels.
AB  - The voltage- and calcium-dependent gating properties of two lens gap-junctional
      hemichannels were compared at the macroscopic and single channel level. In
      solutions containing zero added calcium and 1 mM Mg, chicken Cx56 hemichannels
      were mostly closed at negative potentials and application of depolarizing voltage
      clamp steps elicited a slowly activating outward current. In contrast, chicken
      Cx45.6 hemichannels were predominantly open at negative potentials and rapidly
      closed in response to application of large depolarizing potentials. Another
      difference was that macroscopic Cx45.6 currents were much smaller in size than
      the hemichannel currents induced by oocytes with similar amounts of cRNA for
      Cx56. The aim of this study was to identify which regions of the connexins were
      responsible for the differences in voltage-dependent gating and macroscopic
      current amplitude by constructing a series of chimeric Cx45.6-Cx56 channels. Our
      results show that two charged amino acids that are specific for the alpha3-group
      connexins (R9 in the N-terminus and E43 in the first extracellular loop) are
      important determinants for the difference in voltage-dependent gating between
      Cx45.6 and Cx56 hemichannels; the first transmembrane-spanning domain, M1, is an
      important determinant of macroscopic current magnitude; R9 and E43 are also
      determinants of single channel conductance and rectification.

PMID- 16798802
TI  - Pressure-jump-induced kinetics reveals a hydration dependent folding/unfolding
      mechanism of ribonuclease A.
AB  - Pressure-jump (p-jump)-induced relaxation kinetics was used to explore the energy
      landscape of protein folding/unfolding of Y115W, a fluorescent variant of
      ribonuclease A. Pressure-jumps of 40 MPa amplitude (5 ms dead-time) were
      conducted both to higher (unfolding) and to lower (folding) pressure, in the
      range from 100 to 500 MPa, between 30 and 50 degrees C. Significant deviations
      from the expected symmetrical protein relaxation kinetics were observed. Whereas
      downward p-jumps resulted always in single exponential kinetics, the kinetics
      induced by upward p-jumps were biphasic in the low pressure range and monophasic
      at higher pressures. The relative amplitude of the slow phase decreased as a
      function of both pressure and temperature. At 50 degrees C, only the fast phase
      remained. These results can be interpreted within the framework of a two
      dimensional energy surface containing a pressure- and temperature-dependent
      barrier between two unfolded states differing in the isomeric state of the Asn
      113-Pro-114 bond. Analysis of the activation volume of the fast kinetic phase
      revealed a temperature-dependent shift of the unfolding transition state to a
      larger volume. The observed compensation of this effect by glycerol offers an
      explanation for its protein stabilizing effect.

PMID- 16798804
TI  - Tensorial electrokinetics in articular cartilage.
AB  - Electrokinetic phenomena contribute to biomechanical functions of articular
      cartilage and underlie promising methods for early detection of osteoarthritic
      lesions. Although some transport properties, such as hydraulic permeability, are
      known to become anisotropic with compression, the direction-dependence of
      cartilage electrokinetic properties remains unknown. Electroosmosis experiments
      were therefore performed on adult bovine articular cartilage samples, whereby
      fluid flows were driven by electric currents in directions parallel and
      perpendicular to the articular surface of statically compressed explants.
      Magnitudes of electrokinetic coefficients decreased slightly with compression
      (from approximately -7.5 microL/As in the range of 0-20% compression to -6.0
      microL/As in the 35-50% range) consistent with predictions of microstructure
      based models of cartilage material properties. However, no significant dependence
      on direction of the electrokinetic coupling coefficient was detected, even for
      conditions where the hydraulic permeability tensor is known to be anisotropic.
      This contrast may also be interpreted using microstructure-based models, and
      provides insights into structure-function relationships in cartilage
      extracellular matrix and physical mediators of cell responses to tissue
      compression. Findings support the use of relatively simple isotropic modeling
      approaches for electrokinetic phenomena in cartilage and related materials, and
      indicate that measurement of electrokinetic properties may provide particularly
      robust means for clinical evaluation of cartilage matrix integrity.

PMID- 16798803
TI  - Nanoscale dielectrophoretic spectroscopy of individual immobilized mammalian
      blood cells.
AB  - Dielectrophoretic force microscopy (DEPFM) and spectroscopy have been performed
      on individual intact surface-immobilized mammalian red blood cells.
      Dielectrophoretic force spectra were obtained in situ in approximately 125 ms and
      could be acquired over a region comparable in dimension to the effective diameter
      of a scanning probe microscopy tip. Good agreement was observed between the
      measured dielectrophoretic spectra and predictions using a single-shell cell
      model. In addition to allowing for highly localized dielectric characterization,
      DEPFM provided a simple means for noncontact imaging of mammalian blood cells
      under aqueous conditions. These studies demonstrate the feasibility of using
      DEPFM to monitor localized changes in membrane capacitance in real time with high
      spatial resolution on immobilized cells, complementing previous studies of mobile
      whole cells and cell suspensions.

PMID- 16798805
TI  - Coupling of global and local vibrational modes in dynamic allostery of proteins.
AB  - It is now recognized that internal global protein dynamics play an important role
      in the allosteric function of many proteins. Alterations of protein flexibility
      on effector binding affect the entropic cost of binding at a distant site. We
      present a coarse-grained model for a potential amplification of such entropic
      allostery due to coupling of fast, localized modes to the slow, global modes. We
      show how such coupling can give rise to large compensating entropic and enthalpic
      terms. The model corresponds to the pattern of calorimetry and NMR data from
      experiments on the Met repressor.

PMID- 16798806
TI  - Kinetic properties of GABA rho1 homomeric receptors expressed in HEK293 cells.
AB  - The rho1 subunit of the ionotropic GABA receptors is thought to contribute to the
      formation of the GABA(C) receptors with pharmacological and physiological
      properties distinct from those of GABA(A) receptors. Previous characterization of
      this subunit expressed in the Xenopus oocytes revealed an ion channel with slow
      activation and deactivation and no desensitization, quite different from the
      properties of GABA(C) receptors observed in native cells. We expressed the human
      rho1 subunit in human embryonic kidney (HEK) 293 cells and quantitatively
      characterized the kinetic properties of these receptors using a rapid drug
      application device. The rho1 subunit expressed in HEK293 cells exhibited
      pharmacological and kinetic properties qualitatively identical to those described
      when rho1 was expressed in the oocytes. An apparent desensitizing current
      observed during a constant GABA application was determined to be secondary to an
      E(Cl) shift. Detailed kinetic analyses and parameter estimation for a five-state
      kinetic model revealed that the channel is best described by a set of rate
      constants with a notably faster GABA unbinding K(off) rate compared to the
      parameters proposed for the same subunit expressed in the oocytes. The same
      subunit expressed in hippocampal neurons showed activation and deactivation
      kinetics identical to the current characterized in HEK293 cells. The kinetic
      properties of rho1 subunit expressed in a nonoocyte model system may be better
      described quantitatively by the rate constants presented here.

PMID- 16798808
TI  - Protein-water and protein-buffer interactions in the aqueous solution of an
      intrinsically unstructured plant dehydrin: NMR intensity and DSC aspects.
AB  - Proton NMR intensity and differential scanning calorimetry measurements were
      carried out on an intrinsically unstructured late embryogenesis abundant protein,
      ERD10, the globular BSA, and various buffer solutions to characterize water and
      ion binding of proteins by this novel combination of experimental approaches. By
      quantifying the number of hydration water molecules, the results demonstrate the
      interaction between the protein and NaCl and between buffer and NaCl on a
      microscopic level. The findings overall provide direct evidence that the
      intrinsically unstructured ERD10 not only has a high hydration capacity but can
      also bind a large amount of charged solute ions. In accord, the dehydration
      stress function of this protein probably results from its simultaneous action of
      retaining water in the drying cells and preventing an adverse increase in ionic
      strength, thus countering deleterious effects such as protein denaturation.

PMID- 16798807
TI  - Temperature and composition dependence of the interaction of delta-lysin with
      ternary mixtures of sphingomyelin/cholesterol/POPC.
AB  - The kinetics of carboxyfluorescein efflux induced by the amphipathic peptide
      delta-lysin from vesicles of porcine brain sphingomyelin (BSM), 1-palmitoyl-2
      oleoyl-phosphatidylcholine (POPC), and cholesterol (Chol) were investigated as a
      function of temperature and composition. Sphingomyelin (SM)/Chol mixtures form a
      liquid-ordered (L(o)) phase whereas POPC exists in the liquid-disordered (L(d))
      phase at ambient temperature. delta-Lysin binds strongly to L(d) and poorly to
      L(o) phase. In BSM/Chol/POPC vesicles the rate of carboxyfluorescein efflux
      induced by delta-lysin increases as the POPC content decreases. This is explained
      by the increase of delta-lysin concentration in L(d) domains, which enhances
      membrane perturbation by the peptide. Phase separations in the micrometer scale
      have been observed by fluorescence microscopy in SM/Chol/POPC mixtures for some
      SM, though not for BSM. Thus, delta-lysin must detect heterogeneities (domains)
      in BSM/Chol/POPC on a much smaller scale. Advantage was taken of the inverse
      variation of the efflux rate with the L(d) content of BSM/Chol/POPC vesicles to
      estimate the L(d) fraction in those mixtures. These results were combined with
      differential scanning calorimetry to obtain the BSM/Chol/POPC phase diagram as a
      function of temperature.

PMID- 16798809
TI  - Toward a general method to observe the phosphate groups of phosphoenzymes with
      infrared spectroscopy.
AB  - A general method to study the phosphate group of phosphoenzymes with infrared
      difference spectroscopy by helper enzyme-induced isotope exchange was developed.
      This allows the selective monitoring of the phosphate P-O vibrations in large
      proteins, which provides detailed information on several band parameters. Here,
      isotopic exchange was achieved at the oxygen atoms of the catalytically important
      phosphate group that transiently binds to the sarcoplasmic reticulum Ca(2+)
      ATPase (SERCA1a). [gamma-(18)O(3)]ATP phosphorylated the ATPase, which produced
      phosphoenzyme that was initially isotopically labeled. The helper enzyme
      adenylate kinase regenerated the substrate ATP from ADP (added or generated upon
      ATP hydrolysis) with different isotopic composition than used initially. With
      time this produced the unlabeled phosphoenzyme. The method was tested on the ADP
      insensitive phosphoenzyme state of the Ca(2+)-ATPase for which the vibrational
      frequencies of the phosphate group are known, and it was established that the
      helper enzyme is effective in mediating the isotope exchange process.

PMID- 16798811
TI  - Fast and reversible photoswitching of the fluorescent protein dronpa as evidenced
      by fluorescence correlation spectroscopy.
AB  - Controlling molecular properties through photoirradiation holds great promise for
      its potential for noninvasive and selective manipulation of matter. Photochromism
      has been observed for several different molecules, including green fluorescent
      proteins, and recently the discovery of a novel photoswitchable green fluorescent
      protein called Dronpa was reported. Dronpa displays reversible and highly
      efficient on/off photoswitching of its fluorescence emission, and reversible
      switching of immobilized single molecules of Dronpa with response times faster
      than 20 ms was demonstrated. In this Letter, we expand these observations to
      freely diffusing molecules by using fluorescence correlation spectroscopy with
      simultaneous excitation at 488 and 405 nm. By varying the intensity of
      irradiation at 405 nm, we demonstrate the reversible photoswitching of Dronpa
      under these conditions, and from the obtained autocorrelation functions we
      conclude that this photoswitching can occur within tens of microseconds.

PMID- 16798810
TI  - Molecular simulation of the binding of nerve growth factor peptide mimics to the
      receptor tyrosine kinase A.
AB  - Nerve growth factor (NGF) mimics play an important role for therapies that target
      the receptor tyrosine kinase A (trkA). The N-terminal fragment of the NGF (N
      term@NGF) was previously demonstrated to be an important determinant for affinity
      and specificity in the binding to trkA. Here we use a variety of computational
      tools (contact surface analysis and free energy predictions) to identify residues
      playing a key role for the binding to the receptor. Molecular dynamics
      simulations are then used to investigate the stability of complexes between trkA
      and peptides mimicking N-term@NGF. Steered molecular dynamics calculations are
      finally performed to investigate the process of detaching the peptide from the
      receptor. Three disruptive events are observed, the first involving the breaking
      of all intermolecular interactions except two salt bridges, which break
      subsequently.

PMID- 16798812
TI  - The hydration of the neurotransmitter acetylcholine in aqueous solution.
AB  - Neutron diffraction augmented with hydrogen isotope substitution has been used to
      examine the water structure around the acetylcholine molecular ion in aqueous
      solution. It is shown that the nearest-neighbor water molecules in the region
      around the trimethylammonium headgroup are located either in a ring around the
      central nitrogen atom or between the carbon atoms, forming a sheath around the
      onium group. Moreover the water molecules in this cavity do not bond to the onium
      group but rather form hydrogen bonds with water molecules in the surrounding
      aqueous environment. Given that in the bound state the onium headgroup must be
      completely desolvated, the absence of bonding between the onium headgroup and the
      surrounding water solvent may be selectively favorable to acetylcholine-binding
      in the receptor site. Away from the headgroup, pronounced hydrogen-bonding of
      water to the carbonyl oxygen is observed, but not to the ether oxygen in the
      acetylcholine chain.

PMID- 16798813
TI  - Urea-induced unfolding of the immunity protein Im9 monitored by spFRET.
AB  - We have studied the urea-induced unfolding of the E colicin immunity protein Im9
      using diffusion single-pair fluorescence resonance energy transfer. Detailed
      examination of the proximity ratio of the native and denatured molecules over a
      wide range of urea concentrations suggests that the conformational properties of
      both species are denaturant-dependent. Whereas native molecules become gradually
      more expanded as urea concentration increases, denatured molecules show a
      dramatic dependence of the relationship between proximity ratio and denaturant
      concentration, consistent with substantial compaction of the denatured ensemble
      at low denaturant concentrations. Analysis of the widths of the proximity ratio
      distributions for each state suggests that whereas the native state ensemble is
      relatively narrow and homogeneous, the denatured state may possess heterogeneity
      in mildly denaturing conditions.

PMID- 16798814
TI  - Energetic and structural consequences of desolvation/solvation barriers to
      protein folding/unfolding assessed from experimental unfolding rates.
AB  - Theoretical work has suggested the existence of solvation/desolvation barriers in
      protein folding/unfolding processes. We propose that the energetic and structural
      consequences of such barriers for the folding transition state can be assessed
      from experimental unfolding rates using well-established structure-energetics
      relationships. For a set of proteins of size within the 60-130 number-of-residues
      range, we find energetic effects associated to solvation/desolvation on the order
      of 10(2) kJ/mol. This supports that the folding transition states may be
      characterized by large networks of water-unsatisfied, broken internal contacts.
      In terms of buried surface, we estimate the typical network size to be on the
      order of several thousands of A2, or approximately 50% of the total change in
      accessible surface area upon unfolding. The analyses reported here thus suggest a
      clear structural picture for the different energetic balance of native and
      folding transition states.

PMID- 16798815
TI  - Structured water layers adjacent to biological membranes.
AB  - Water amid the restricted space of crowded biological macromolecules and at
      membrane interfaces is essential for cell function, though the structure and
      function of this "biological water" itself remains poorly defined. The force
      required to remove strongly bound water is referred to as the hydration force and
      due to its widespread importance, it has been studied in numerous systems. Here,
      by using a highly sensitive dynamic atomic force microscope technique in
      conjunction with a carbon nanotube probe, we reveal a hydration force with an
      oscillatory profile that reflects the removal of up to five structured water
      layers from between the probe and biological membrane surface. Further, we find
      that the hydration force can be modified by changing the membrane fluidity. For
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine gel (Lbeta) phase bilayers, each
      oscillation in the force profile indicates the force required to displace a
      single layer of water molecules from between the probe and bilayer. In contrast,
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine fluid (Lalpha) phase bilayers at 60
      degrees C and 1,2-dioleoyl-sn-glycero-3-phosphocholine fluid (Lalpha) phase
      bilayers at 24 degrees C seriously disrupt the molecular ordering of the water
      and result predominantly in a monotonic force profile.

PMID- 16798816
TI  - SERCA overexpression reduces hydroxyl radical injury in murine myocardium.
AB  - Hydroxyl radicals (*OH) are involved in the pathogenesis of ischemia-reperfusion
      injury and are observed in clinical situations, including acute heart failure,
      stroke, and myocardial infarction. Acute transient exposure to *OH causes an
      intracellular Ca(2+) overload and leads to impaired contractility. We
      investigated whether upregulation of sarcoplasmic reticulum Ca(2+)-ATPase
      function (SERCA) can attenuate *OH-induced dysfunction. Small, contracting right
      ventricular papillary muscles from wild-type (WT) SERCA1a-overexpressing
      (transgenic, TG) and SERCA2a heterogeneous knockout (HET) mice were directly
      exposed to *OH. This brief 2-min exposure led to a transient elevation of
      diastolic force (F(dia)) and depression of developed force (F(dev)). In WT mice,
      F(dia) increased to 485 +/- 49% and F(dev) decreased to 11 +/- 3%. In sharp
      contrast, in TG mice F(dia) increased only to 241 +/- 17%, whereas F(dev)
      decreased only to 51 +/- 5% (P < 0.05 vs. WT). In HET mice, F(dia) rose more than
      WT (to 597 +/- 20%, P < 0.05), whereas F(dev) was reduced in a similar amount.
      After approximately 45 min after *OH exposure, a new steady state was reached:
      F(dev) returned to 37 +/- 6% and 32 +/- 6%, whereas F(dia) came back to 238 +/-
      28% and 292 +/- 17% in WT and HET mice, respectively. In contrast, the sustained
      dysfunction was significantly less in TG mice: F(dia) and F(dev) returned to 144
      +/- 20% and 67 +/- 6%, respectively. Before exposure to *OH, there is decrease in
      phospholamban (PLB) phosphorylation at Ser16 (pPLBSer16) and PLB phosphorylation
      at Thr17 (pPLBThr17) in TG mice and an increase in pPLBSer16 and pPLBThr17 in HET
      mice versus WT. After exposure to *OH there is decrease in pPLBSer16 in WT, TG,
      and HET mice but no significant change in the level of pPLBThr17 in any group.
      The results indicate that SERCA overexpression can reduce the *OH-induced
      contractile dysfunction in murine myocardium, whereas a reduced SR Ca(2+)-ATPase
      activity aggravates this injury. Loss of pPLB levels at Ser16 likely amplifies
      the differences observed in injury response.

PMID- 16798817
TI  - Exercise training improves aortic depressor nerve sensitivity in rats with
      ischemia-induced heart failure.
AB  - Exercise training improves arterial baroreflex control in heart failure (HF)
      rabbits. However, the mechanisms involved in the amelioration of baroreflex
      control are unknown. We tested the hypothesis that exercise training would
      increase the afferent aortic depressor nerve activity (AODN) sensitivity in
      ischemic-induced HF rats. Twenty ischemic-induced HF rats were divided into
      trained (n = 11) and untrained (n = 9) groups. Nine normal control rats were also
      studied. Power spectral analysis of pulse interval, systolic blood pressure,
      renal sympathetic nerve activity (RSNA), and AODN were analyzed by means of
      autoregressive parametric spectral and cross-spectral algorithms. Spontaneous
      baroreflex sensitivity of heart rate (HR) and RSNA were analyzed during
      spontaneous variation of systolic blood pressure. Left ventricular end-diastolic
      pressure was higher in HF rats compared with that in the normal control group (P
      = 0.0001). Trained HF rats had a peak oxygen uptake higher than untrained rats
      and similar to normal controls (P = 0.01). Trained HF rats had lower low
      frequency [1.8 +/- 0.2 vs. 14.6 +/- 3 normalized units (nu), P = 0.0003] and
      higher high-frequency (97.9 +/- 0.2 vs. 85.0 +/- 3 nu, P = 0.0005) components of
      pulse interval than untrained rats. Trained HF rats had higher spontaneous
      baroreceptor sensitivity of HR (1.19 +/- 0.2 vs. 0.51 +/- 0.1 ms/mmHg, P = 0.003)
      and RSNA [2.69 +/- 0.4 vs. 1.29 +/- 0.3 arbitrary units (au)/mmHg, P = 0.04] than
      untrained rats. In HF rats, exercise training increased spontaneous AODN
      sensitivity toward normal levels (trained HF rats, 1,791 +/- 215; untrained HF
      rats, 1,150 +/- 158; and normal control rats, 2,064 +/- 327 au/mmHg, P = 0.05).
      In conclusion, exercise training improves AODN sensitivity in HF rats.

PMID- 16798818
TI  - Upregulation of intermediate-conductance Ca2+-activated K+ channel (IKCa1)
      mediates phenotypic modulation of coronary smooth muscle.
AB  - A hallmark of smooth muscle cell (SMC) phenotypic modulation in atherosclerosis
      and restenosis is suppression of SMC differentiation marker genes, proliferation,
      and migration. Blockade of intermediate-conductance Ca(2+)-activated K(+)
      channels (IKCa1) has been shown to inhibit restenosis after carotid balloon
      injury in the rat; however, whether IKCa1 plays a role in SMC phenotypic
      modulation is unknown. Our objective was to determine the role of IKCa1 channels
      in regulating coronary SMC phenotypic modulation and migration. In cultured
      porcine coronary SMCs, platelet-derived growth factor-BB (PDGF-BB) increased TRAM
      34 (a specific IKCa1 inhibitor)-sensitive K(+) current 20-fold; increased IKCa1
      promoter histone acetylation and c-jun binding; increased IKCa1 mRNA
      approximately 4-fold; and potently decreased expression of the smooth muscle
      differentiation marker genes smooth muscle myosin heavy chain (SMMHC), smooth
      muscle alpha-actin (SMalphaA), and smoothelin-B, as well as myocardin.
      Importantly, TRAM-34 completely blocked PDGF-BB-induced suppression of SMMHC,
      SMalphaA, smoothelin-B, and myocardin and inhibited PDGF-BB-stimulated migration
      by approximately 50%. Similar to TRAM-34, knockdown of endogenous IKCa1 with
      siRNA also prevented the PDGF-BB-induced increase in IKCa1 and decrease in SMMHC
      mRNA. In coronary arteries from high fat/high cholesterol-fed swine demonstrating
      signs of early atherosclerosis, IKCa1 expression was 22-fold higher and SMMHC,
      smoothelin-B, and myocardin expression significantly reduced in proliferating vs.
      nonproliferating medial cells. Our findings demonstrate that functional
      upregulation of IKCa1 is required for PDGF-BB-induced coronary SMC phenotypic
      modulation and migration and support a similar role for IKCa1 in coronary SMC
      during early coronary atherosclerosis.

PMID- 16798819
TI  - Passive pericardial constraint protects against stretch-induced vulnerability to
      atrial fibrillation in rabbits.
AB  - Atrial fibrillation is more common in conditions with elevated atrial pressure
      and can be induced experimentally with acute increases in atrial pressure. We
      examined the effect of increased atrial pressure with and without pericardial
      constraint to better separate the effects of increased pressure and atrial
      stretch. In Langendorff-perfused rabbit hearts with intact pericardium, after
      ligating the pulmonary and caval veins, intra-atrial pressures were increased in
      a stepwise manner by adjusting the pulmonary outflow cannula. Rapid burst pacing
      was applied to induce atrial fibrillation at increasing intra-atrial pressures
      from 0 to 24 cmH(2)O. The atrial refractory period was recorded at each pressure
      using a single extra stimulus. The protocol was repeated after the pericardium
      was removed. When the pericardium was intact, atrial stretch was limited by
      passive constraint, and sustained atrial fibrillation could not be induced
      despite atrial pressures in excess of 20 cmH(2)O. In contrast, when the
      pericardium was removed, atrial fibrillation could be reliably induced when
      atrial pressure exceeded 15 cmH(2)O. This suggests that the electrophysiological
      effects of acute atrial volume loading rely on atrial stretch rather than
      increased atrial pressure alone.

PMID- 16798820
TI  - In SHR aorta, calcium ionophore A-23187 releases prostacyclin and thromboxane A2
      as endothelium-derived contracting factors.
AB  - In mature spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY),
      acetylcholine and the calcium ionophore A-23187 release endothelium-derived
      contracting factors (EDCFs), cyclooxygenase derivatives that activate thromboxane
      endoperoxide (TP) receptors on vascular smooth muscle. The EDCFs released by
      acetylcholine are most likely prostacyclin and prostaglandin (PG)H(2), whereas
      those released by A-23187 remain to be identified. Isometric tension and the
      release of PGs were measured in rings of isolated aortas of WKY and SHR. A-23187
      evoked the endothelium-dependent release of prostacyclin, thromboxane A(2),
      PGF(2alpha), PGE(2), and possibly PGH(2) (PGI(2) >> thromboxane A(2) =
      PGF(2alpha) = PGE(2)). In SHR aortas, the release of prostacyclin and thromboxane
      A(2) was significantly larger in response to A-23187 than to acetylcholine. In
      response to the calcium ionophore, the release of thromboxane A(2) was
      significantly larger in aortas of SHR than in those of WKY. In both strains of
      rat, the inhibition of cyclooxygenase-1 prevented the release of PGs and the
      occurrence of endothelium-dependent contractions. Dazoxiben, the thromboxane
      synthase inhibitor, abolished the A-23187-dependent production of thromboxane
      A(2) and inhibited by approximately one-half the endothelium-dependent
      contractions. U-51605, an inhibitor of PGI synthase, reduced the release of
      prostacyclin elicited by A-23187 but induced a parallel increase in the
      production of PGE(2) and PGF(2alpha), suggestive of a PGH(2) spillover, which was
      associated with the enhancement of the endothelium-dependent contractions. These
      results indicate that in the aorta of SHR and WKY, the endothelium-dependent
      contractions elicited by A-23187 involve the release of thromboxane A(2) and
      prostacyclin with a most likely concomitant contribution of PGH(2).

PMID- 16798822
TI  - Comparison of Ca2+-handling properties of canine pulmonary vein and left atrial
      cardiomyocytes.
AB  - Cardiac tissue in the pulmonary vein sleeves plays an important role in clinical
      atrial fibrillation. Mechanisms leading to pulmonary vein activity in atrial
      fibrillation remain unclear. Indirect experimental evidence points to pulmonary
      vein Ca(2+) handling as a potential culprit, but there are no direct studies of
      pulmonary vein cardiomyocyte Ca(2+) handling in the literature. We used the
      Ca(2+)-sensitive dye indo-1 AM to study Ca(2+) handling in isolated canine
      pulmonary vein and left atrial myocytes. Results were obtained at 35 degrees C
      and room temperature in cells from control dogs and in cardiomyocytes from dogs
      subjected to 7-day rapid atrial pacing. We found that basic Ca(2+)-transient
      properties (amplitude: 186 +/- 28 vs. 216 +/- 25 nM; stimulus to half-decay time:
      192 +/- 9 vs. 192 +/- 9 ms; atria vs. pulmonary vein, respectively, at 1 Hz),
      beat-to-beat regularity, propensity to alternans, beta-adrenergic response
      (amplitude increase at 0.4 Hz: 96 +/- 52 vs. 129 +/- 61%), number of spontaneous
      Ca(2+)-transient events after Ca(2+) loading (in normal Tyrode: 0.9 +/- 0.2 vs.
      1.3 +/- 0.2; with 1 microM isoproterenol: 7.6 +/- 0.3 vs. 5.1 +/- 1.8
      events/min), and caffeine-induced Ca(2+)-transient amplitudes were not
      significantly different between atrial and pulmonary vein cardiomyocytes. In an
      arrhythmia-promoting model (dogs subjected to 7-day atrial tachypacing), Ca(2+)
      transient amplitude and kinetics were the same in cells from both pulmonary veins
      and atrium. In conclusion, the similar Ca(2+)-handling properties of canine
      pulmonary vein and left atrial cardiomyocytes that we observed do not support the
      hypothesis that intrinsic Ca(2+)-handling differences account for the role of
      pulmonary veins in atrial fibrillation.

PMID- 16798821
TI  - Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled
      myocardium after myocardial infarction.
AB  - The renin-angiotensin system plays an important role in cardiovascular
      homeostasis by contributing to the regulation of blood volume, blood pressure,
      and vascular tone. Because AT(1) receptors have been described in the coronary
      microcirculation, we investigated whether ANG II contributes to the regulation of
      coronary vascular tone and whether its contribution is altered during exercise.
      Since the renin-angiotensin system is activated after myocardial infarction,
      resulting in an increase in circulating ANG II, we also investigated whether the
      contribution of ANG II to the regulation of vasomotor tone is altered after
      infarction. Twenty-six chronically instrumented swine were studied at rest and
      while running on a treadmill at 1-4 km/h. In 13 swine, myocardial infarction was
      induced by ligation of the left circumflex coronary artery. Blockade of AT(1)
      receptors (irbesartan, 1 mg/kg iv) had no effect on myocardial O(2) consumption
      but resulted in an increase in coronary venous O(2) tension and saturation both
      at rest and during exercise, reflecting coronary vasodilation. Despite increased
      plasma levels of ANG II after infarction and maintained coronary arteriolar AT(1)
      receptor levels, the vasodilation evoked by irbesartan was significantly reduced
      both at rest and during exercise. In conclusion, despite elevated plasma levels,
      the vasoconstrictor influence of ANG II on the coronary circulation in vivo is
      reduced after myocardial infarction. This reduction in ANG II-induced coronary
      vasoconstriction may serve to maintain perfusion of the remodeled myocardium.

PMID- 16798823
TI  - Exercise training blunts microvascular rarefaction in the metabolic syndrome.
AB  - Reduced skeletal muscle microvessel density (MVD) in the obese Zucker rat (OZR)
      model of the metabolic syndrome is a function of a chronic reduction in vascular
      nitric oxide (NO) bioavailability. Previous studies suggest that exercise can
      improve NO bioavailability and reduce chronic inflammation and that low vascular
      NO bioavailability may be associated with impaired angiogenic responses via
      increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. As such, we
      hypothesized that chronic exercise (EX) would increase NO bioavailability in OZR
      and blunt microvascular rarefaction through reduced MMP activity, and potentially
      via altered plasma cytokine levels. Ten weeks of treadmill exercise (1 h/day, 5
      days/wk, 22 m/min) reduced body mass and fasting insulin and triglyceride levels
      in EX-OZR vs. sedentary (SED) OZR. In EX-OZR, gastrocnemius muscle MVD was
      improved by 19 +/- 4%, whereas skeletal muscle arteriolar dilation and conduit
      arterial methacholine-induced NO release were increased. In EX-OZR, functional
      hyperemia was improved vs. SED-OZR, and minimum vascular resistance within
      perfused gastrocnemius muscle was reduced, although no change in arteriolar
      stiffness was identified. Western blotting and gelatin zymography demonstrated
      that neither expression nor activity of MMP-2 or MMP-9 was altered in skeletal
      muscle of EX vs. SED animals. Plasma markers of inflammation associated with
      angiogenesis, monocyte chemoattractant protein-1 and IL-1beta, were increased in
      SED-OZR and were reduced with training, whereas IL-13 was reduced in SED-OZR and
      increased with exercise. These data suggest that exercise-induced improvements in
      skeletal muscle MVD in OZR are associated with increased NO bioavailability and
      may stem from altered inflammatory profiles rather than MMP function.

PMID- 16798824
TI  - Is there a need for another model on the pulsatile nature of coronary blood flow?

PMID- 16798825
TI  - Nitrite as a vascular endocrine nitric oxide reservoir that contributes to
      hypoxic signaling, cytoprotection, and vasodilation.
AB  - Accumulating evidence suggests that the simple and ubiquitous anion salt, nitrite
      (NO(2)(-)), is a physiological signaling molecule with potential roles in
      intravascular endocrine nitric oxide (NO) transport, hypoxic vasodilation,
      signaling, and cytoprotection after ischemia-reperfusion. Human and animal
      studies of nitrite treatment and NO gas inhalation provide evidence that nitrite
      mediates many of the systemic therapeutic effects of NO gas inhalation, including
      peripheral vasodilation and prevention of ischemia-reperfusion-mediated tissue
      infarction. With regard to nitrite-dependent hypoxic signaling, biochemical and
      physiological studies suggest that hemoglobin possesses an allosterically
      regulated nitrite reductase activity that reduces nitrite to NO along the
      physiological oxygen gradient, potentially contributing to hypoxic vasodilation.
      An expanded consideration of nitrite as a hypoxia-dependent intrinsic signaling
      molecule has opened up a new field of research and therapeutic opportunities for
      diseases associated with regional hypoxia and vasoconstriction.

PMID- 16798826
TI  - Enhanced alpha1-adrenergic trophic activity in pulmonary artery of hypoxic
      pulmonary hypertensive rats.
AB  - Mechanisms that induce the excessive proliferation of vascular wall cells in
      hypoxic pulmonary hypertension (PH) are not fully understood. Alveolar hypoxia
      causes sympathoexcitation, and norepinephrine can stimulate alpha(1)-adrenoceptor
      (alpha(1)-AR)-dependent hypertrophy/hyperplasia of smooth muscle cells and
      adventitial fibroblasts. Adrenergic trophic activity is augmented in systemic
      arteries by injury and altered shear stress, which are key pathogenic stimuli in
      hypoxic PH, and contributes to neointimal formation and flow-mediated
      hypertrophic remodeling. Here we examined whether norepinephrine stimulates
      growth of the pulmonary artery (PA) and whether this is augmented in PH. PA from
      normoxic and hypoxic rats [9 days of 0.1 fraction of inspired O(2) (Fi(O(2)))]
      was studied in organ culture, where wall tension, Po(2), and Pco(2) were
      maintained at values present in normal and hypoxic PH rats. Norepinephrine
      treatment for 72 h increased DNA and protein content modestly in normoxic PA
      (+10%, P < 0.05). In hypoxic PA, these effects were augmented threefold (P <
      0.05), and protein synthesis was increased 34-fold (P < 0.05). Inferior thoracic
      vena cava from normoxic or hypoxic rats was unaffected. Norepinephrine-induced
      growth in hypoxic PA was dose dependent, had efficacy greater than or equal to
      endothelin-1, required the presence of wall tension, and was inhibited by
      alpha(1A)-AR antagonist. In hypoxic pulmonary vasculature, alpha(1A)-AR was
      downregulated the least among alpha(1)-AR subtypes. These data demonstrate that
      norepinephrine has trophic activity in the PA that is augmented by PH. If evident
      in vivo in the pulmonary vasculature, adrenergic-induced growth may contribute to
      the vascular hyperplasia that participates in hypoxic PH.

PMID- 16798827
TI  - High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in
      rats: role of xanthine oxidase-derived superoxide anion.
AB  - Obesity frequently leads to the development of hypertension. We hypothesized that
      high-fat diet (HFD)-induced obesity impairs the endothelium-dependent dilation of
      arterioles. Male Wistar rats were fed with normal (control) or HFD (60% of
      saturated fat, for 10 wk). In rats with HFD, body weight, mean arterial blood
      pressure, and serum insulin, cholesterol, and glucose were elevated. In isolated
      gracilis muscle arterioles (diameter: approximately 160 microm) of HFD, rat
      dilations to ACh (at 1 microM, maximum: 83 +/- 3%) and histamine (at 10 microM,
      maximum: 16 +/- 4%) were significantly (P < 0.05) decreased compared with those
      of control responses (maximum: 90 +/- 2 and 46 +/- 4%, respectively). Dilations
      to the NO donor sodium nitroprusside were similar in the two groups. Inhibition
      of NO synthesis by N(omega)-nitro-l-arginine methyl ester reduced ACh- and
      histamine-induced dilations in control arterioles but had no effect on
      microvessels of HFD rats. The superoxide dismutase mimetic Tiron or xanthine
      oxidase inhibitor allopurinol enhanced ACh (maximum: 90 +/- 2 and 93 +/- 2%,
      respectively)- and histamine (maximum: 30 +/- 7 and 37 +/- 8%, respectively)
      induced dilations in HFD arterioles, whereas the NAD(P)H oxidase inhibitor
      apocynin had no significant effect. Correspondingly, in carotid arteries of HFD
      rats, an enhanced superoxide production was shown by lucigenin-enhanced
      chemiluminescence, in association with an increased xanthine oxidase, but not
      NAD(P)H oxidase activity. In addition, a marked xanthine oxidase immunostaining
      was detected in the endothelial layer of the gracilis arterioles of HFD, but not
      in control rats. These findings suggest that, in obese rats, NO mediation of
      endothelium-dependent dilation of skeletal muscle arterioles is reduced because
      of an enhanced xanthine oxidase-derived superoxide production. These alterations
      demonstrate substantial dysregulation of arteriolar tone by the endothelium in
      HFD-induced obesity, which may contribute to disturbed tissue blood flow and
      development of increased peripheral resistance.

PMID- 16798828
TI  - Opening mitoKATP increases superoxide generation from complex I of the electron
      transport chain.
AB  - Opening the mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) increases
      levels of reactive oxygen species (ROS) in cardiomyocytes. This increase in ROS
      is necessary for cardioprotection against ischemia-reperfusion injury; however,
      the mechanism of mitoK(ATP)-dependent stimulation of ROS production is unknown.
      We examined ROS production in suspensions of isolated rat heart and liver
      mitochondria, using fluorescent probes that are sensitive to hydrogen peroxide.
      When mitochondria were treated with the K(ATP) channel openers diazoxide or
      cromakalim, their ROS production increased by 40-50%, and this effect was blocked
      by 5-hydroxydecanoate. ROS production exhibited a biphasic dependence on
      valinomycin concentration, with peak production occurring at valinomycin
      concentrations that catalyze about the same K(+) influx as K(ATP) channel
      openers. ROS production decreased with higher concentrations of valinomycin and
      with all concentrations of a classical protonophoretic uncoupler. Our studies
      show that the increase in ROS is due specifically to K(+) influx into the matrix
      and is mediated by the attendant matrix alkalinization. Myxothiazol stimulated
      mitoK(ATP)-dependent ROS production, whereas rotenone had no effect. This
      indicates that the superoxide originates in complex I (NADH:ubiquinone
      oxidoreductase) of the electron transport chain.

PMID- 16798829
TI  - Effect of pravastatin on left ventricular mass in the two-kidney, one-clip
      hypertensive rats.
AB  - We have demonstrated that myocardial ATP-sensitive potassium (K(ATP)) channels
      are implicated in the development of cardiac hypertrophy in hyperlipidemic
      rabbits. We investigated the effect of pravastatin on development of ventricular
      hypertrophy in male normolipidemic Wistar rats with two-kidney, one-clip (2K1C)
      hypertension and whether the attenuated hypertrophic effect was via activation of
      K(ATP) channels. Twenty-four hours after the left renal artery was clipped, rats
      were treated with one of the following therapies for 8 wk: vehicle, nicorandil
      (an agonist of K(ATP) channels), pravastatin, glibenclamide (an antagonist of
      K(ATP) channels), hydralazine, nicorandil plus glibenclamide, or pravastatin plus
      glibenclamide. Systolic blood pressure, relative left ventricular (LV) weight,
      and cardiomyocyte sizes significantly increased in vehicle-treated 2K1C rats
      compared with those in sham-operated rats. Treatment with either nicorandil or
      pravastatin significantly attenuated LV hypertrophy/body weight compared with the
      vehicle, which was further confirmed by downregulation of LV atrial natriuretic
      peptide mRNA. Nicorandil-induced effects were abolished by administering
      glibenclamide. Similarly, pravastatin-induced beneficial effects were reversed by
      the addition of glibenclamide, implicating K(ATP) channels as the relevant
      target. A dissociation between the effects of blood pressure and cardiac
      structure was noted because pravastatin and hydralazine reduced arterial pressure
      similarly. These results suggest a crucial role of cardiac K(ATP) channel system
      in the development of ventricular hypertrophy in the 2K1C hypertensive rats.
      Pravastatin is endowed with cardiac antihypertrophic properties probably through
      activation of K(ATP) channels, independent of lipid and hemodynamic changes.

PMID- 16798830
TI  - Controlled reperfusion after hypothermic heart preservation inhibits
      mitochondrial permeability transition-pore opening and enhances functional
      recovery.
AB  - We investigated whether low-pressure reperfusion may attenuate postischemic
      contractile dysfunction, limits necrosis and apoptosis after a prolonged
      hypothermic ischemia, and inhibits mitochondrial permeability transition-pore
      (MPTP) opening. Isolated rats hearts (n = 72) were exposed to 8 h of cold
      ischemia and assigned to the following groups: 1) reperfusion with low pressure
      (LP = 70 cmH(2)O) and 2) reperfusion with normal pressure (NP = 100 cmH(2)O).
      Cardiac function was assessed during reperfusion using the Langendorff model.
      Mitochondria were isolated, and the Ca(2+) resistance capacity (CRC) of the MPTP
      was determined. Malondialdehyde (MDA) production, caspase-3 activity, and
      cytochrome c were also assessed. We found that functional recovery was
      significantly improved in LP hearts with rate-pressure product averaging 30,380
      +/- 1,757 vs. 18,000 +/- 1,599 mmHg/min in NP hearts (P < 0.01). Necrosis,
      measured by triphenyltetrazolium chloride staining and creatine kinase leakage,
      was significantly reduced in LP hearts (P < 0.01). The CRC was increased in LP
      heart mitochondria (P < 0.01). Caspase-3 activity, cytochrome c release, and MDA
      production were reduced in LP hearts (P < 0.001 and P < 0.01). This study
      demonstrated that low-pressure reperfusion after hypothermic heart ischemia
      improves postischemic contractile dysfunction and attenuates necrosis and
      apoptosis. This protection could be related to an inhibition of mitochondrial
      permeability transition.

PMID- 16798831
TI  - Rat mesenteric arterial dilator response to 11,12-epoxyeicosatrienoic acid is
      mediated by activating heme oxygenase.
AB  - 11,12-Epoxyeicosatrienoic acid (11,12-EET), a potent vasodilator produced by the
      endothelium, acts on calcium-activated potassium channels and shares biological
      activities with the heme oxygenase/carbon monoxide (HO/CO) system. We examined
      whether activation of HO mediates the dilator action of 11,12-EET, and that of
      the other EETs, on rat mesenteric arteries. Dose-response curves (10(-9) to 10(
      6) M) to 5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET, and ACh (10(-9) to 10(-4) M)
      were evaluated in preconstricted (10(-6) mol/l phenylephrine) mesenteric arteries
      (<350 microm diameter) in the presence or absence of 1) the cyclooxygenase
      inhibitor indomethacin (2.8 microM), 2) the HO inhibitor chromium mesoporphyrin
      (CrMP) (15 microM), 3) the soluble guanylyl cyclase (GC) inhibitor ODQ (10
      microM), and 4) the calcium-activated potassium channel inhibitor iberiotoxin (25
      nM). The vasodilator response to 11,12-EET was abolished by CrMP and iberiotoxin,
      whereas indomethacin and ODQ had no effect. In contrast, the effect of ACh was
      attenuated by ODQ but not by CrMP. The vasodilator effect of 8,9-EET, like that
      of 11,12-EET, was greatly attenuated by HO inhibition. In contrast, the
      mesenteric vasodilator response to 5,6-EET was independent of both HO and GC,
      whereas that to 14,15-EET demonstrated two components, an HO and a GC, of equal
      magnitude. Incubation of mesenteric microvessels with 11,12-EET caused a 30%
      increase in CO release, an effect abolished by inhibition of HO. We conclude that
      the rat mesenteric vasodilator action of 11,12-EET is mediated via an increase in
      HO activity and an activation of calcium-activated potassium channels.

PMID- 16798832
TI  - A 2D FE model of the heart demonstrates the role of the pericardium in
      ventricular deformation.
AB  - During pulmonary artery constriction (PAC), an experimental model of acute right
      ventricular (RV) pressure overload, the interventricular septum flattens and
      inverts. Finite element (FE) analysis has shown that the septum is subject to
      axial compression and bending when so deformed. This study examines the effects
      of acute PAC on the left ventricular (LV) free wall and the role the pericardium
      may play in these effects. In eight open-chest anesthetized dogs, LV, RV, aortic,
      and pericardial pressures were recorded under control conditions and with PAC.
      Model dimensions were derived from two-dimensional echocardiography minor-axis
      images of the heart. At control (pericardium closed), FE analysis showed that the
      septum was concave to the LV; stresses in the LV, RV, and septum were low; and
      the pericardium was subject to circumferential tension. With PAC, RV end
      diastolic pressure exceeded LV pressure and the septum inverted. Compressive
      stresses developed circumferentially in the septum out to the RV insertion
      points, forming an arch-like pattern. Sharp bending occurred near the insertion
      points, accompanied by flattening of the LV free wall. With the pericardium open,
      the deformations and stresses were different. The RV became much larger,
      especially with PAC. With PAC, the arch-like circumferential stresses still
      developed in the septum, but their magnitudes were reduced, compared with the
      pericardium-closed case. There was no free wall inversion and flattening was
      less. From these FE results, the pericardium has a significant influence on the
      structural behavior of the septum and the LV and RV free walls. Furthermore, the
      deformation of the heart is dependent on whether the pericardium is open or
      closed.

PMID- 16798833
TI  - Interferon-alpha and somatostatin analog in patients with gastroenteropancreatic
      neuroendocrine carcinoma: single agent or combination?
AB  - In most cases gastro-enteropancreatic neuroendocrine tumors grow slowly.
      Interferon-alpha and somatostatin analogs have shown symptomatic, biochemical,
      and, in a minority of cases, antiproliferative activity. Generally, they are
      proposed as single-agent therapy. However, based on in vitro and in vivo
      evidence, the combined use of these drugs was proposed in several non-randomized
      trials, indicating that there is an additive effect of the combination.
      Nevertheless, the three randomized trials published so far did not show a
      statistically significant survival benefit for the combination compared to the
      same agents alone, even though an advantage for the combination came out in all
      three studies. On the other hand, data from non-randomized trials would justify
      the sequential use of the two drugs or the combination after progression on
      single agent therapy. Therefore, at present the up-front combined use of
      interferon-alpha and somatostatin analog is not justified, whereas it could be
      indicated after progression to single-agent therapy. Further larger,
      international, prospective, randomized, multicentric clinical trials studying
      homogeneous populations would be necessary to give a final answer, but the rarity
      and heterogeneity of this malignancy does not assure that it will be possible.

PMID- 16798834
TI  - Role of endocrine responsiveness and adjuvant therapy in very young women (below
      35 years) with operable breast cancer and node negative disease.
AB  - BACKGROUND: There is limited knowledge about prognosis, and treatment effects in
      young women with node-negative disease. PATIENTS AND METHODS: We evaluated
      biological features, treatment recommendations and prognosis for 841
      premenopausal patients with pT1-3, pN0 and M0, operated from 1997 to 2001.
      RESULTS: Patients below 35 years (101, 12%) were more likely to have tumors > 2
      cm (35.6% versus 24.2%, P = 0.002), grade 3 (48.5% versus 31.9%, P = 0.009) and
      with elevated Ki-67 expression (62.4% versus 50.7%, P = 0.002). At the
      multivariate analysis a statistically significant difference in disease-free
      survival (DFS, HR 4.44; 95% CI 2.53 to 7.78, P < 0.0001), risk of distant
      metastases (DDFS) (HR 3.23; 95% CI 1.32 to 7.94, P = 0.011) and overall survival
      (OS) (HR 2.89; 95% CI 1.06 to 7.87, P = 0.038) was observed for younger versus
      older patients and in the subgroup with endocrine responsive tumors (DFS, HR
      5.17, 95% CI 2.72-9.83, P = < 0.0001; DDFS, 3.76, 95% CI 1.33-10.6, P = 0.013;
      OS, 4.71, 95% CI 1.09-20.4, P = 0.039 ). CONCLUSIONS: Compared with less young,
      very young patients with endocrine responsive and node-negative breast cancer
      have a worse prognosis. Tailored treatments should be explored in this cohort of
      patients.

PMID- 16798837
TI  - Oxaliplatin and capecitabine (Xelox) in association with highly active
      antiretroviral therapy in advanced hepatocarcinoma HIV/HCV-infected patients.

PMID- 16798838
TI  - Cbl and Akt regulate CXCL8-induced and CXCR1- and CXCR2-mediated chemotaxis.
AB  - CXCL8 (IL-8) plays an important role in the pathogenesis of a variety of
      inflammatory diseases. However, little is known about the signaling pathways that
      regulate CXCL8-induced chemotaxis. Here, we found that CXCL8 treatment of CXCR1-
      and CXCR2-over-expressing L1.2 cells (CXCR1-L1.2 and CXCR2-L1.2, respectively)
      induced the phosphorylation of Cbl and Akt. The tyrosine kinase inhibitor
      Tyrphostin A9, phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 as well as
      proteasome inhibitors significantly blocked the CXCL8-induced chemotaxis of L1.2
      cells and human neutrophils. We further found that stimulation with CXCL8
      enhanced the association of the PI3K subunit p85 with Cbl. Additionally, over
      expression of wild-type Cbl and G306E-Cbl (mutation in the tyrosine kinase
      binding domain) inhibited chemotaxis by approximately 50% as compared with the
      vector control, whereas the 70Z mutant (deletion in the RING finger domain) did
      not reduce migration. However, wild-type Cbl or its mutants had no effect on the
      CXCL8-induced activation of MAPK, indicating that Cbl specifically modulated
      CXCL8-induced chemotaxis. Furthermore, over-expression of the kinase-dead Akt
      mutant decreased CXCL8-induced chemotaxis by 60% and diminished Cbl
      phosphorylation as compared with the vector control. The CXCL8-induced
      phosphorylation of Cbl was also reduced when cells were pre-treated with the PI3K
      inhibitor LY294002. Lastly, we have shown that pre-treatment of L1.2 cells with
      the proteasome inhibitor Lactacystin blocks CXCL8-induced internalization of the
      CXCR1 and CXCR2 receptors. These studies provide new information regarding CXCL8
      induced signaling pathways that may regulate chemotaxis and receptor
      internalization.

PMID- 16798839
TI  - Toll-like receptor 9-independent aggravation of glomerulonephritis in a novel
      model of SLE.
AB  - The generation of anti-DNA auto-antibodies is characteristic for the human
      autoimmune condition systemic lupus erythematosus (SLE) and its animal models.
      However, the contribution of the toll-like receptor (TLR) system of innate
      immunity receptors and, in particular, TLR9 to this B cell-mediated autoimmune
      process remains controversial. Here we report that in a novel murine model of
      SLE, based on hyper-reactive B cell activation mediated by mutant phospholipase
      Cg2, the genetic deficiency of TLR9 does not protect from spontaneous anti-DNA
      auto-antibody formation and glomerulonephritis. On the contrary, disease
      induction is aggravated and additional nucleolar antibody specificity develops in
      autoimmune TLR9-deficient mice. In vitro studies demonstrate that, in autoimmune
      prone mice, dual signaling via the B cell receptor and non-CpG DNA results in
      synergistic B cell activation in a TLR9-independent manner. These results suggest
      that engagement of a TLR9-independent DNA activation pathway may promote
      autoimmunity, while TLR9 signaling can ameliorate SLE-like immune pathology in
      vivo.

PMID- 16798840
TI  - House dust mite allergen Der p 1 elevates the release of inflammatory cytokines
      and expression of adhesion molecules in co-culture of human eosinophils and
      bronchial epithelial cells.
AB  - House dust mite (HDM) is a common allergen of allergic asthma. Eosinophils are
      principal effector cells of allergic inflammation and their adhesion onto human
      bronchial epithelial cells is mediated by a CD18-intracellular adhesion molecule
      1 (ICAM-1)-dependent interaction. We studied the effects of HDM Dermatophagoides
      pteronyssinus (Der p) 1 on the activation of eosinophils and bronchial epithelial
      BEAS-2B cells. Cytokines and adhesion molecules were measured using flow
      cytometry. Transcription factor nuclear factor-kappaB (NF-kappaB) and activator
      protein-1 (AP-1) and signaling molecule p38 mitogen-activated protein kinase
      (MAPK) were analyzed using electromobility shift assay and western blot,
      respectively. Der p 1 protein was found to potently induce the release of IL
      1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha and granulocyte macrophage
      colony-stimulating factor from eosinophils. Such induction was further up
      regulated for IL-6 and IL-10, and down-regulated for TNF-alpha and IL-1beta in
      eosinophil-BEAS-2B cells co-culture. Surface expression of CD18 and ICAM-1 on
      eosinophils was greatly increased by Der p 1; such inductive effect on ICAM-1 was
      also found to be more prominent on BEAS-2B cells from the co-culture than BEAS-2B
      cells alone. Der p 1 was found to activate NF-kappaB and AP-1 activity in
      eosinophils alone and in co-culture and BEAS-2B cells in co-culture. Moreover,
      Der p 1 could activate p38 MAPK in BEAS-2B cells and eosinophils alone and in co
      culture. Selective inhibition of NF-kappaB, AP-1 and p38 MAPK resulted in
      differential suppression of the Der p 1-induced cytokine release and adhesion
      molecule expression. As an allergen, HDM could therefore induce the release of
      inflammatory cytokines and expression of adhesion molecules from the interaction
      of human eosinophils and bronchial epithelial cells.

PMID- 16798841
TI  - Human germinal center T cells are unique Th cells with high propensity for
      apoptosis induction.
AB  - Collaborative interactions between T(h) cells and B cells are necessary for the
      production of antibody responses to most protein antigens and for the generation
      of memory B cells in germinal centers (GCs). Although it is well established that
      T(h) cells are pivotal for the GC reaction, the mechanisms that control the
      homeostasis of T(h) cells during the GC response remain largely unknown. Here we
      show that, unlike other effector T cells, a significant number of
      CD4(+)CD45RO(+)CD57(+) T cells, which are the major T(h) cells residing in the
      GCs, are undergoing apoptosis in vivo. CD4(+)CD45RO(+)CD57(+) GC T cells exhibit
      similar sensitivities to apoptotic signals and to caspase inhibitors as immature
      thymocytes. Moreover, CD4(+)CD45RO(+)CD57(+) GC T cells express a unique profile
      of genes that control apoptosis and cell cycle, providing possible molecular
      mechanisms for the high rates of apoptotic death of these T(h) cells in the GCs.

PMID- 16798842
TI  - Urinary estrogen and progesterone metabolite concentrations in menstrual cycles
      of fertile women with non-conception, early pregnancy loss or clinical pregnancy.
AB  - BACKGROUND: Knowledge is limited of how estrogen and progesterone variability in
      fertile women are associated with achieving pregnancy. METHODS: From 1996 to
      1998, we enrolled 347 textile workers without hormone treatment in Anhui, China,
      who provided daily urine and data upon stopping contraception for up to 1 year
      until clinical pregnancy. Urinary hCG was assayed to detect conception and early
      pregnancy losses. We compared urinary concentrations of estrone conjugates
      (E(1)C) and pregnanediol-3-glucuronide (PdG) in 266 clinical pregnancies, 63
      early pregnancy losses and 272 non-conception cycles from 347 women and also in
      94 clinical pregnancy and 94 non-conception cycles from the same women. RESULTS:
      Using generalized estimating equations and relative to 266 clinical pregnancy
      cycles, log(E(1)C) was lower in 272 non-conception cycles [beta = -0.3 ng/mg
      creatinine (Cr); SE = 0.1; P < 0.0001]. On average, daily E(1)C was 18 ng/mg Cr
      lower in non-conception cycles than in clinical pregnancy cycles. Relative to 94
      clinical pregnancy cycles, log(E(1)C) was lower in 94 non-conception cycles (beta
      = -0.4 ng/mg Cr; SE = 0.1; P < 0.0001) from the same women (average difference in
      daily E(1)C was 20 ng/mg Cr). The odds of E(1)C less than the 10th percentile
      (<30 ng/mg Cr) were higher in early pregnancy loss cycles [odds ratio (OR) = 4.8;
      P = 0.0027] than in clinical pregnancy cycles in the early luteal phase. Compared
      with clinical pregnancy cycles, log(PdG) concentrations were lower in non
      conception cycles during the follicular phase, but this analysis lacked power for
      multiple testing. CONCLUSIONS: Estrogen concentrations varied from cycle to
      cycle, and higher estrogen was associated with achieving clinical pregnancy.

PMID- 16798843
TI  - Purification, functional characterization, cloning, and identification of mutants
      of a seed-specific arabinan hydrolase in Arabidopsis.
AB  - This work describes the purification and characterization of an enzyme that
      exhibits arabinan hydrolase activity in seeds of Arabidopsis thaliana. The
      enzyme, designated XYL3, had an apparent molecular mass of 80 kDa when purified
      to homogeneity, and was identified using MALDI-TOF (matrix-assisted laser
      desorption ionization-time of flight) as a putative beta-D-xylosidase that
      belongs to family 3 of glycoside hydrolases encoded by gene At5g09730. XYL3
      hydrolysed synthetic substrates such as p-nitrophenyl-alpha-L-arabinofuranoside
      and p-nitrophenyl-beta-D-xyloside with similar catalytic efficiency. XYL3
      released L-arabinose from (1-->5)-alpha-L-arabinofuranobiose, arabinoxylan, sugar
      beet arabinan, and debranched arabinan. The enzyme hydrolysed both arabinosyl
      substituted side group residues and terminal arabinofuranosyl residues (1-->5)
      alpha-linked to the arabinan backbone. This indicates that XYL3 is able to
      degrade all terminal arabinosyl residues and suggests that it participates in the
      in-vivo hydrolysis of arabinan. Analysis of gene expression patterns by semi
      quantitative RT-PCR, in-situ hybridization and a promoter-GUS fusion demonstrated
      that AtBX3 was specifically expressed in the seed endosperm at the globular stage
      of the embryo. Immunolocalization using LM6 anti-arabinan antisera found that
      arabinan, the XYL3 substrate, was also present in this seed tissue. T-DNA null
      mutants for AtBX3 were identified. The mutant plants lacked the alpha-L
      arabinofuranosidase and beta-D-xylosidase activities corresponding to XYL3.
      Mutants showed reduced seed size and are delayed in seedling germination compared
      with the wild type.

PMID- 16798844
TI  - Sugar effects on membrane damage during desiccation of pea embryo protoplasts.
AB  - Desiccation tolerance of protoplasts isolated from germinating pea (Pisum sativum
      L. cv. 'Alaska') embryonic axes depends, in part, on the osmotic strength and
      composition of the suspending medium. To determine the reason for this dependence
      and whether treatment with different solutions results in different types of
      damage, protoplast recovery and survival were assessed after dehydration to a
      range of water contents. Protoplasts were derived from germinating axes that had
      intermediate desiccation tolerance. Protoplasts were isolated and resuspended in
      buffers containing sucrose/raffinose (85:15, w/w) or sorbitol, which were
      isotonic or hypertonic to the cells of the embryonic axis, then were flash-dried
      to a range of water contents. Protoplasts were rehydrated and stained with
      fluorescein diacetate (FDA) to assess survival and to estimate two types of
      membrane injury: lysis and the loss of semipermeability. In all treatments,
      protoplast survival dropped sharply during the initial phase of dehydration due
      to lysis. Protoplast survival was greater in hypertonic sucrose/raffinose buffer
      than in isotonic sucrose/raffinose buffer, or in the latter made hypertonic by
      the addition of sorbitol. When sorbitol was substituted for sucrose/raffinose in
      either the isolation or desiccation buffer, or both, protoplast survival at
      intermediate and low hydrations decreased due to a loss of membrane
      semipermeability. The results indicate that additional sucrose/raffinose is
      beneficial for the desiccation tolerance of protoplasts, the benefit is not due
      to a simple osmotic effect, and the benefit is greatest at water contents less
      than 0.5 g g(-1) DW, where the presence of the sugars appears to protect membrane
      semipermeability.

PMID- 16798845
TI  - VSP accumulation and cold-inducible gene expression during autumn hardening and
      overwintering of alfalfa.
AB  - This study describes the time-course of the accumulation of total soluble
      proteins (TSPs) and vegetative storage proteins (VSPs) and of the transcripts of
      cold-inducible (CI) and VSP-encoding genes in taproots of two alfalfa cultivars
      (AC Caribou and Europe) during their acclimation to natural autumn hardening and
      overwintering conditions in eastern Canada. The impact of a defoliation in
      September on these winter hardening-related changes was also assessed. Both
      concentrations and pools of VSPs increased significantly between early September
      and mid-October and remained unchanged thereafter, concomitantly with the
      disappearance of VSP-encoding transcripts. Other soluble protein constituents
      continued to increase later in the autumn and early winter and accounted for
      nearly 60% of taproot TSP pools in winter. As a result, VSP abundance relative to
      TSPs decreased markedly during the winter. The increase in the levels of CI
      transcripts was induced by lowering temperatures, and distinct patterns suggest
      differences in the regulation of their accumulation. RNA analyses revealed that
      the accumulation of VSP transcripts during the autumn precedes the accumulation
      of CI transcripts. Autumn defoliation interrupted the accumulation of both TSPs
      and VSPs during autumn hardening and repressed the transcript levels of two CI
      genes differentially between cultivars. The well-documented impact of autumn
      defoliation on the vigour of spring regrowth and long-term persistence of alfalfa
      could be related to its negative impact on the accumulation of VSPs and TSPs and
      on the expression of genes encoding CI proteins potentially involved in cold
      tolerance and pathogen resistance.

PMID- 16798846
TI  - Anticipated yield loss in field-grown soybean under elevated ozone can be avoided
      at the expense of leaf growth during early reproductive growth stages in
      favourable environmental conditions.
AB  - Ozone is a powerful oxidizing agent which is responsible for more damage to
      vegetation than any other air pollutant. In this study, leaf growth,
      photosynthesis, and carbohydrate content were analysed during the seed-filling
      growth stage of field-grown soybeans exposed to ambient air and 1.2 times ambient
      ozone concentration using a Free Air Concentration Enrichment (FACE) facility. By
      contrast to predictions based on controlled-environment and open-top chamber
      studies, final yield did not differ between treatments, although the cultivar
      used here was sensitive to ozone damage: growth and carbohydrate content of upper
      canopy leaves was reduced during the seed-filling stage in which an ozone-induced
      decrease of photosynthesis was present. However, 2004 was an ideal growing season
      in central Illinois and the cumulative ozone indices were lower than in previous
      years. Still, the results indicate that the anticipated yield loss under ozone
      concentrations was avoided at the expense of leaf growth, as reserves were
      diverted from vegetative to reproductive organs.

PMID- 16798847
TI  - Cytokinin and auxin inhibit abscisic acid-induced stomatal closure by enhancing
      ethylene production in Arabidopsis.
AB  - Cytokinins and auxins are major phytohormones involved in various aspects of
      plant growth and development. These phytohormones are also known to antagonize
      the effects of abscisic acid (ABA) on stomatal movement, and to affect ethylene
      biosynthesis. As ethylene has an antagonistic effect on ABA-induced stomatal
      closure, the possibility that the antagonistic effects of these phytohormones on
      ABA were mediated through ethylene biosynthesis was investigated. Both the
      cytokinin, 6-benzyladenine (BA), and the auxin, 1-naphthaleneacetic acid (NAA),
      antagonized ABA-induced stomatal closure in a manner similar to that following
      application of the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid
      (ACC). However, these effects were negated when ethylene signalling, perception,
      or biosynthesis were blocked. As stomatal aperture is regulated by changes in
      guard cell volume, ABA application was found to reduce the volume of the guard
      cell protoplasts (GCP). It was found that BA, NAA, or ACC application compensated
      perfectly for the reduction in GCP volume by ABA application in WT plants. The
      above observations suggest that cytokinins and auxins inhibit ABA-induced
      stomatal closure through the modulation of ethylene biosynthesis, and that
      ethylene inhibits the ABA-induced reduction of osmotic pressure in the guard
      cells.

PMID- 16798848
TI  - Field studies on the regulation of abscisic acid content and germinability during
      grain development of barley: molecular and chemical analysis of pre-harvest
      sprouting.
AB  - To investigate whether the regulation of abscisic acid (ABA) content was related
      to germinability during grain development, two cDNAs for 9-cis-epoxycarotenoid
      dioxygenase (HvNCED1 and HvNCED2) and one cDNA for ABA 8'-hydroxylase
      (HvCYP707A1), which are enzymes thought to catalyse key regulatory steps in ABA
      biosynthesis and catabolism, respectively, were cloned from barley (Hordeum
      vulgare L.). Expression and ABA-quantification analysis in embryo revealed that
      HvNCED2 is responsible for a significant increase in ABA levels during the early
      to middle stages of grain development, and HvCYP707A1 is responsible for a rapid
      decrease in ABA level thereafter. The change in the embryonic ABA content of
      imbibing grains following dormancy release is likely to reflect changes in the
      expression patterns of HvNCEDs and HvCYP707A1. A major change between dormant and
      after-ripened grains occurred in HvCYP707A1; the increased expression of
      HvCYP707A1 in response to imbibition, followed by a rapid ABA decrease and a high
      germination percentage, was observed in the after-ripened grains, but not in the
      dormant grains. Under field conditions, HvNCED2 showed the same expression level
      and pattern during grain development in 2002, 2003, and 2004, indicating that
      HvNCED2 expression is regulated in a growth-dependent manner in the grains. By
      contrast, HvNCED1 and HvCYP707A1 showed a different expression pattern in each
      year, indicating that the expression of these genes is affected by environmental
      conditions during grain development. The varied expression levels of these genes
      during grain development and imbibition, which would have effects on the activity
      of ABA biosynthesis and catabolism, might be reflected, in part, in the
      germinability in field-grown barley.

PMID- 16798850
TI  - The influence of cytosolic phosphorylating glyceraldehyde 3-phosphate
      dehydrogenase (GAPC) on potato tuber metabolism.
AB  - The aim of this work was to investigate the importance of cytosolic
      phosphorylating glyceraldehyde 3-phosphate dehydrogenase (GAPC) in potato
      carbohydrate metabolism. For this purpose, the cytosolic isoform of
      phosphorylating GAPC was cloned and used for an antisense approach to generate
      transgenic potato plants that exhibited constitutively decreased GAPDH activity.
      Potato lines with decreased activities of phosphorylating GAPC exhibited no major
      changes in either whole-plant or tuber morphology. However, the levels of 3
      phosphoglycerate were decreased in leaves of the transformants. A broad metabolic
      phenotyping of tubers from the transformants revealed an increase in sucrose and
      UDPglucose content, a decrease in the glycolytic intermediates 3-phosphoglycerate
      and phosphoenolpyruvate but little change in the levels of other metabolites.
      Moreover, the transformants displayed no differences in cold sweetening with
      respect to the wild type. Taken together these data suggest that phosphorylating
      GAPC plays only a minor role in the regulation of potato metabolism. The results
      presented here are discussed in relation to current models regarding primary
      metabolism in the potato tuber parenchyma.

PMID- 16798849
TI  - High-throughput virus-induced gene-silencing approach to assess the functional
      relevance of a moisture stress-induced cDNA homologous to lea4.
AB  - The abiotic stress-responsive cDNA database and their expression profiles suggest
      that stress genes are many and diverse. However, characterization and validation
      of their functional significance has been a constraint to assessing their role in
      imparting tolerance. Virus-induced gene silencing (VIGS) is a potential option
      for assessing the functional significance of stress genes. Here the effectiveness
      of VIGS to silence the expression of an ABA-responsive lea4 (late embryogenic
      abundant) gene involved in stress tolerance is documented. In the present study,
      low moisture-stress protocols were developed in such a way that the plants
      experienced the desired stress level when silencing the target stress gene using
      VIGS was at a maximum. The functional relevance of a groundnut (Arachis hypogaea)
      subtracted-stress cDNA clone putative lea4 was examined by VIGS in tomato. A 400
      bp fragment of lea4 was cloned into tobacco rattle virus-based VIGS vector to
      trigger post-transcriptional gene silencing by Agrobacterium-mediated inoculation
      in tomato plants. In silenced plants only lea4 transcripts showed a substantial
      decline, whereas the expression of other known stress-responsive genes such as
      apx (ascorbate peroxidase) and elip (early light-induced protein) were unaltered.
      Under moderate moisture stress, the silenced plants showed enhanced
      susceptibility as measured by cell viability, superoxide radical activity, and
      cell osmotic adjustment. This approach illustrates the potential benefits of VIGS
      in identifying functional relevance of low moisture stress-responsive genes. It
      is also demonstrated that heterologous probes with a fairly high degree of
      homology to the native genes can be used to study the functional relevance of
      stress-responsive genes using VIGS.

PMID- 16798851
TI  - Equilibration of adenylates in the mitochondrial intermembrane space maintains
      respiration and regulates cytosolic metabolism.
AB  - Adenylate kinase (AK) uses one each of Mg-complexed and free adenylates as
      substrates in both directions of its reaction. It is very active in the
      mitochondrial intermembrane space (IMS), but is absent from the mitochondrial
      matrix where low [ADP] upon intensive respiration limits the respiratory rate. AK
      activity in the IMS is linked to ATP/ADP exchange across the inner mitochondrial
      membrane by using ATP (imported from the matrix) and AMP as substrates, the
      latter provided by apyrase and other AMP-generating reactions. The ADP formed by
      AK is exported to the matrix (in exchange for ATP), providing a mechanism for
      regeneration of ADP during respiration. From the AK equilibrium, and taking pH
      values characteristic of subcellular compartments, [Mg2+] in the IMS is
      calculated as 0.4-0.5 mM and in the cytosol as 0.2-0.3 mM, whereas the
      MgATP:MgADP ratio in the IMS and cytosol is 6-9 and 10-15, respectively. These
      represent optimal conditions for transport of adenylates (via the maintenance of
      an ATPfree:ADPfree ratio close to 1) and mitochondrial respiratory rates (via the
      maintenance of submillimolar [ADPfree] in the IMS). This, in turn, has important
      consequences for mitochondrial and cytosolic metabolism, including regulation of
      the protein phosphorylation rate (via changes in the MgATP:AMPfree ratio) and
      allosteric regulation of mitochondrial and cytosolic enzymes. Metabolomic
      consequences are discussed in connection with the calculation of metabolic fluxes
      from subcompartmental distributions of total adenylates and Mg2+.

PMID- 16798852
TI  - Up- and down-regulation of Fragaria x ananassa O-methyltransferase: impacts on
      furanone and phenylpropanoid metabolism.
AB  - A complex mixture of hundreds of substances determines strawberry (Fragaria x
      ananassa) aroma, but only approximately 15 volatiles are considered as key
      flavour compounds. Of these, 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is
      regarded as the most important, but it is methylated further by FaOMT (Fragaria x
      ananassa O-methyltransferase) to 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF)
      during the ripening process. It is shown here that transformation of strawberry
      with the FaOMT sequence in sense and antisense orientation, under the control of
      the cauliflower mosaic virus 35S promoter, resulted in a near total loss of DMMF,
      whereas the levels of the other volatiles remained unchanged. FaOMT repression
      also affected the ratio of feruloyl 1-O-beta-D-glucose and caffeoyl 1-O-beta-D
      glucose, indicating a dual function of the enzyme in planta. Thus, FaOMT is
      involved in at least two different biochemical pathways in ripe strawberry fruit.

PMID- 16798853
TI  - Quantitative contributions of blue light and PAR to the photocontrol of plant
      morphogenesis in Trifolium repens (L.).
AB  - Shade-avoidance is a major adaptive response of plants, and is usually considered
      to be controlled by phytochromes through the perception of changes in the red:far
      red light ratio. However, few studies on the effects of blue light (BL) and of
      light intensity [photosynthetically active radiation (PAR)] on light-grown plants
      have been conducted, especially concerning changes in PAR at constant BL. The
      objective here was to quantify the photocontrol of aerial morphogenesis by BL and
      PAR. Experiments were conducted varying BL and PAR independently, with three BL
      levels (4, 38, and 83 micromol m(-2) s(-1)) at constant PAR (300 micromol m(-2)
      s(-1)) and three PAR levels (338, 705, and 163 micromol m(-2) s(-1)) at constant
      BL (36 micromol m(-2) s(-1)). Effects on morphogenetic processes were analysed as
      quantitative modulations of ontogenic trends and response curves were produced.
      White clover (Trifolium repens L.) was used, as it is a typical shade-avoider
      displaying the whole syndrome of shade-avoidance in a purely vegetative stage.
      Morphological responses were strongly controlled by both BL and PAR changes,
      through antagonist effects on leaf appearance rate and additive effects on
      petiole elongation. All the other responses appeared to be the indirect
      consequences of changes in the leaf appearance rates. BL acted as a light signal
      for plant morphogenesis. However, the PAR control probably implicates two
      distinct mechanisms, such as a trophic effect and a signal. Both PAR and BL
      actions involved organ-specific differences, which are central in the control of
      the shade-avoidance responses.

PMID- 16798854
TI  - Brief report: initial testing of scales measuring parent and adolescent
      Perceptions of Adolescents' Assumption of Diabetes Management.
AB  - OBJECTIVE: This study tested parallel adolescent and parent versions of the
      Perceptions of Adolescents' Assumption of Diabetes Management scales. METHODS:
      First, 78 items developed from interview data were reviewed by a panel of
      adolescent and diabetes experts. Next, the scales were piloted with 43
      adolescents with type 1 diabetes and their parents and, finally, tested with 100
      dyads. Item and principal component analyses were performed. RESULTS: Following
      content validity and item analyses, five and four items remained in the
      advantages and disadvantages scales, respectively. One factor accounted for
      between 54 and 63% of variance, and internal consistency reliability ranged
      between .78 and .84 for the various versions of the scales. CONCLUSIONS: The
      Perceptions of Adolescents' Assumption of Diabetes Management scales show promise
      as parsimonious and reliable tools for use in research and practice related to
      parent-adolescent relationships in regard to adolescents' assumption of diabetes
      management.

PMID- 16798856
TI  - Leveraging your research--mapping our future.

PMID- 16798857
TI  - Bone remodeling in post-menopausal osteoporosis.
AB  - Bone mass in the skeleton is dependent on the coordinated activities of bone
      forming osteoblasts and bone-resorbing osteoclasts in discrete bone multi
      cellular units. Remodeling of bone in these units is important not only for
      maintaining bone mass, but also to repair microdamage, to prevent accumulation of
      too much old bone, and for mineral homeostasis. The activities of osteoblasts and
      osteoclasts are controlled by a variety of hormones and cytokines, as well as by
      mechanical loading. Most importantly, sex hormones are very crucial for keeping
      bone mass in balance, and the lack of either estrogen or testosterone leads to
      decreased bone mass and increased risk for osteoporosis. The prevalence of
      osteoporotic fractures is increasing dramatically in the Western part of the
      world and is a major health problem in many countries. In the present review, the
      cellular and molecular mechanisms controlling bone remodeling and the influence
      of sex hormones on these processes are summarized. In a separate paper in this
      issue, the pathogenesis of post-menopausal osteoporosis will be compared with
      that of inflammation-induced bone remodeling, including the evidence for and
      against the hypothesis that concomitant post-menopausal osteoporotic disease
      influences the progression of periodontal disease.

PMID- 16798858
TI  - Inflammation-induced bone remodeling in periodontal disease and the influence of
      post-menopausal osteoporosis.
AB  - During physiological conditions, the skeleton is remodeled in so-called bone
      multi-cellular units. Such units have been estimated to exist at 1-2 x 10(6)
      sites in the adult skeleton. The number and activities of these units are
      regulated by a variety of hormones and cytokines. In post-menopausal
      osteoporosis, lack of estrogen leads to increased numbers of bone multi-cellular
      units and to uncoupling of bone formation and bone resorption, resulting in too
      little bone laid down by osteoblasts compared with the amount of bone resorbed by
      osteoclasts. Inflammatory processes in the vicinity of the skeleton, e.g.,
      marginal and apical periodontitis, will affect the remodeling of the nearby bone
      tissue in such a way that, in most patients, the amount of bone resorbed exceeds
      that being formed, resulting in net bone loss (inflammation-induced osteolysis).
      In some patients, however, inflammation-induced bone formation exceeds
      resorption, and a sclerotic lesion will develop. The cellular and molecular
      pathogenetic mechanisms in inflammation-induced osteolysis and sclerosis are
      discussed in the present review. The cytokines believed to be involved in
      inflammation-induced remodeling are very similar to those suggested to play
      crucial roles in post-menopausal osteoporosis. In patients with periodontal
      disease and concomitant post-menopausal osteoporosis, the possibility exists that
      the lack of estrogen influences the activities of bone cells and immune cells in
      such a way that the progression of alveolar bone loss will be enhanced. In the
      present paper, the evidence for and against this hypothesis is presented.

PMID- 16798859
TI  - Taste loss and recovery following radiation therapy.
AB  - Previous investigators have reported deficits in taste acuity in patients
      following radiation therapy for oropharyngeal cancer. In the present longitudinal
      study, 13 patients (mean age = 51.6 yrs) received conventional or
      hyperfractionated radiotherapy (63-76.8 Gy) for primary tumors of the oropharynx.
      One or both parotid glands and at least two-thirds of the tongue were included in
      the radiation field. Smell recognition and taste detection thresholds were
      determined at baseline, 1 month, 6 months, and 1 year post-radiation. Differences
      for smell recognition and the 4 taste qualities were assessed (independently) at
      the 4 time intervals, with a one-way ANOVA. Smell recognition was unaffected by
      radiation. There were significant elevations in thresholds for sweet (p < 0.005),
      salty (p < 0.005), bitter (p < 0.005), and sour (p< 0.001) during radiation
      therapy that were restored to baseline levels at 6 months and 1 year after
      radiation. This study demonstrated that radiation-induced taste deficits can be
      recovered by 6 months.

PMID- 16798860
TI  - Protective effect of the dental pellicle against erosive challenges in situ.
AB  - The acquired dental pellicle helps prevent erosion, but the protection level is
      unknown. This in situ study tested whether a two-hour pellicle protects against
      different erosive challenges by orange juice. Subjects wore palatal appliances
      loaded with either enamel or dentin specimens. Pellicle was allowed to form, or
      not (control), on the surfaces of the specimens intra-orally for 2 hrs before the
      erosive challenges of 0 (control), 10, 20, and 30 minutes' duration. Specimens
      were randomly removed from the appliances after each challenge. Percentage of
      surface microhardness change (%SMC) was determined for the enamel specimens, and
      that of mineral loss and lesion depth for the dentin specimens. Enamel specimens
      with the pellicle showed a significantly lower %SMC, only after the 10-minute
      challenge. No protection was found for dentin. It was concluded that the acquired
      pellicle reduced dental erosion, but that this effect was limited to the less
      severe erosive challenge on enamel surfaces.

PMID- 16798861
TI  - In situ mineral loss inhibition by CO2 laser and fluoride.
AB  - Laser and fluoride treatments have been shown to inhibit enamel demineralization
      in the laboratory. However, the intra-oral effects of this association have not
      been tested. This study assessed in situ the effect of a Transversely Excited
      Atmospheric CO2 laser (lambda = 9.6 mum) and the use of pressure fluoridated
      dentifrice on enamel demineralization. During two 14-day phases, 17 volunteers
      wore palatal appliances containing human enamel slabs assigned to treatment
      groups, as follows: (1) non-fluoride dentifrice, (2) CO2 laser irradiation plus
      non-fluoride dentifrice, (3) fluoride dentifrice, and (4) CO2 laser irradiation
      plus fluoride dentifrice. A 20% sucrose solution was dripped onto the slabs 8
      times per day. The specimens treated with laser and/or fluoridated dentifrice
      presented a significantly lower mineral loss when compared with those from the
      non-fluoride dentifrice group. The results suggested that CO2 laser treatment of
      enamel inhibits demineralization in the human mouth, being more effective when
      associated with fluoride.

PMID- 16798862
TI  - Survival of ART and amalgam restorations in permanent teeth of children after 6.3
      years.
AB  - The null hypothesis tested was that there is no difference in the survival
      percentages of all restorations placed through the Atraumatic Restorative
      Treatment (ART) approach, with high-viscosity glass ionomer, and those produced
      through the traditional approach, with amalgam (TA), in the permanent dentitions
      of children after 6.3 years. Using a parallel group design, we randomly assigned
      a total of 370 children, aged 6 to 9 years, to the ART group and 311 children,
      also aged 6 to 9 years, to the TA group. Eight dentists placed a total of 1117
      single- and multiple-surface restorations. The cumulative survival percentages
      for ART glass-ionomer restorations were statistically significantly higher than
      those of amalgam restorations at all time intervals except the first (p < or =
      0.044). After 6.3 years, the cumulative survival percentages of ART and amalgam
      restorations were 66.1% (SE = 3.1%) and 57.0% (SE = 3.3%), respectively. We
      concluded that the restorations produced with the ART approach, with high
      viscosity glass ionomer, survived longer than those produced with the traditional
      approach, with amalgam, in the permanent teeth of young children.

PMID- 16798863
TI  - Increase in RANKL: OPG ratio in synovia of patients with temporomandibular joint
      disorder.
AB  - Although a recent study suggested the involvement of RANKL and osteoprotegerin
      (OPG) in the pathogenesis of bone-destructive disease, no study has focused on
      the RANKL:OPG ratio in the synovial fluid of patients with temporomandibular
      joint (TMJ) disorder. This communication reports on the concentrations of RANKL
      and OPG in synovial fluid from TMJ patients and healthy control individuals. In
      contrast to an unchanged concentration of RANKL, a strong decrease in the
      concentration of OPG was detected in the synovial fluid from patients with TMJ
      internal derangement. Treatment with the synovial fluid of osteoarthritis (OA)
      patients resulted in the high production of osteoclast-like cells from blood
      mononuclear cells in vitro, as well as in pit formation in dentin slices. The
      addition of anti-RANKL IgG or OPG attenuated OA-synovial fluid-induced osteoclast
      formation, suggesting that the increase in the RANKL:OPG ratio in the
      microenvironment of the joint has the potential to induce osteoclastogenesis in
      TMJ osteoarthritis.

PMID- 16798864
TI  - Transplanted endothelial cells enhance orthotopic bone regeneration.
AB  - The aim of this study was to determine if endothelial cells could enhance bone
      marrow stromal-cell-mediated bone regeneration in an osseous defect. Using poly
      lactide-co-glycolide scaffolds as cell carriers, we transplanted bone marrow
      stromal cells alone or with endothelial cells into 8.5-mm calvarial defects
      created in nude rats. Histological analyses of blood vessel and bone formation
      were performed, and microcomputed tomography (muCT) was used to assess
      mineralized bone matrix. Though the magnitude of the angiogenic response between
      groups was the same, muCT analysis revealed earlier mineralization of bone in the
      co-transplantation condition. Ultimately, there was a significant increase (40%)
      in bone formation in the co-transplantation group (33 +/- 2%), compared with the
      transplantation of bone marrow stromal cells alone (23 +/- 3%). Analysis of these
      data demonstrates that, in an orthotopic site, transplanted endothelial cells can
      influence the bone-regenerative capacity of bone marrow stromal cells.

PMID- 16798865
TI  - Mandibular biomechanics and development of the human chin.
AB  - The development of the chin, a feature unique to humans, suggests a close
      functional linkage between jaw biomechanics and symphyseal architecture. The
      present study tests the hypothesis that the presence of a chin changes strain
      patterns in the loaded mandible. Using an anatomically correct 3-D model of a
      dentate mandible derived from a CT scan image, we analyzed strain patterns during
      incisal and molar biting. We then constructed a second mandible, without a chin,
      by 'defeaturing' the first model. Strain patterns of the second model were then
      compared and contrasted to the first. Our main finding was that chinned and non
      chinned mandibles follow closely concordant patterns of strain distribution. The
      results suggest that the development of the human chin is unrelated to the
      demands placed on the mandible during function.

PMID- 16798866
TI  - Gelled calcium polyphosphate matrices delay antibiotic release.
AB  - Introducing a gelling step during antibiotic incorporation has previously been
      found to delay vancomycin delivery from a calcium polyphosphate matrix intended
      for local treatment of bone infections. This study examined the general
      applicability of this approach using cefuroxime, a lower-molecular-weight
      antibiotic with different charge characteristics compared with those of
      vancomycin. A calcium polyphosphate/cefuroxime paste was "gelled" in disk form in
      a humid environment for 5 or 24 hours prior to drying. Antibiotic release in Tris
      buffered saline under gentle agitation was monitored over a seven-day period.
      While non-gelled samples clearly exhibited a burst release, the gelling process
      significantly retarded early antibiotic release from five- and 24-hour gelled
      matrices, yielding a constant release rate over the first four days. Cefuroxime
      incorporation did not appear to alter matrix structure or degradation. Overall,
      this non-aggressive process effectively trapped cefuroxime and reduced its
      release rate, suggesting its potential applicability with molecularly diverse
      therapeutic agents.

PMID- 16798867
TI  - Omega-3 fatty acid effect on alveolar bone loss in rats.
AB  - Gingival inflammation and alveolar bone resorption are hallmarks of adult
      periodontitis, elicited in response to oral micro-organisms such as Porphyromonas
      gingivalis. We hypothesized that omega (omega)-3 fatty acids (FA) dietary
      supplementation would modulate inflammatory reactions leading to periodontal
      disease in infected rats. Rats were fed fish oil (omega-3 FA) or corn oil (n-6
      FA) diets for 22 weeks and were infected with P. gingivalis. Rats on the omega-3
      FA diet exhibited elevated serum levels of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), documenting diet-induced changes. PCR analyses
      demonstrated that rats were orally colonized by P. gingivalis; increased IgG
      antibody levels substantiated this infection. P. gingivalis-infected rats treated
      with omega-3 FA had significantly less alveolar bone resorption. These results
      demonstrated the effectiveness of an omega-3 FA-supplemented diet in modulating
      alveolar bone resorption following P. gingivalis infection, and supported that
      omega-3 FA may be a useful adjunct in the treatment of periodontal disease.

PMID- 16798868
TI  - Condylar mineralization following mandibular distraction in rats.
AB  - The impact of mandibular distraction on condyles is poorly understood. To examine
      how condylar mineralization is affected, we performed distraction in 128 one
      month-old rapidly and 126 three-month-old slowly growing rats. The rate of
      distraction was 0.0 mm (sham), 0.2 mm (slow), 0.4 mm (moderate), or 0.6 mm
      (rapid). From 7 to 9 rats from each rate (n = 29-32) were killed at 4 time
      periods (D6, D10, D24, and D38) following osteotomy. Calcein and alizarin were
      injected 6 and 3 days, respectively, prior to death. Methacrylate-embedded
      sagittal condylar sections were examined under epifluorescence, and mineral
      apposition rates were measured. Results indicated that: (1) rapidly growing rats
      showed higher mineral apposition rates (p < 0.01-0.001) than did slowly growing
      rats; (2) mineral apposition rates were lower in distracted sides at all times in
      rapidly growing rats (p < 0.05-0.01), while this side-dependency was seen only at
      D24 in slowly growing rats (p < 0.05); and (3) distraction rates had little
      effect on mineral apposition rates. Thus, mandibular distraction decreases
      condylar mineral apposition rates, but only in rapidly growing rats, which is
      related to surgery and its functional consequences, not to the distraction rate.

PMID- 16798869
TI  - Increase of galanin in trigeminal ganglion during tooth movement.
AB  - It is known that nerve fibers containing neuropeptides such as galanin increase
      in the periodontal ligament during experimental tooth movement. However, the
      origin of galanin-containing nerve fibers in the periodontal ligament remains
      unclear. This study was conducted to examine our hypothesis that the increased
      galanin nerve fibers have a sensory neuronal origin, and that the peptide is
      associated with pain transmission and/or periodontal ligament remodeling during
      experimental tooth movement. In control rats, galanin-immunoreactive trigeminal
      ganglion cells were very rare and were observed predominantly in small ganglion
      cells. After 3 days of experimental tooth movement, galanin-immunoreactive
      trigeminal ganglion cells significantly increased, and the most marked increase
      was observed at 5 days after experimental tooth movement. Furthermore, their cell
      size spectrum also significantly changed after 3 and 5 days of movement: Medium
      sized and large trigeminal ganglion cells began expressing, and continued to
      express, galanin until 14 days after experimental tooth movement. These findings
      suggest that the increase of galanin in the periodontal ligament during
      experimental tooth movement at least partially originates from trigeminal
      ganglion neurons and may play a role in pain transmission and/or periodontal
      remodeling.

PMID- 16798870
TI  - Single-channel recordings of TREK-1 K+ channels in periodontal ligament
      fibroblasts.
AB  - The periodontal ligament (PDL) works as a suspensory ligament when external
      mechanical stress is placed on the teeth. PDL fibroblasts, the principal cells in
      the PDL, are responsible for many PDL functions. We hypothesized that
      mechanosensitive ion channels are present in human PDL fibroblasts, which are
      capable of responding to mechanical stress during normal function of the tissue.
      Using patch-clamp techniques, we detected mechanosensitive TREK-1 K+ channels (a
      member of the two-pore-domain K+ channel family), whose single-channel
      conductance was 104 pS in symmetrical K+-rich solutions. The open probability of
      the channel was low in the quiescent state, but it was strongly increased by the
      induction of membrane stretch. Arachidonic acid also enhanced the channel
      activity. RT-PCR and immunocytochemical observations showed the expression of
      TREK-1 K+ channels in PDL fibroblasts. The results suggest that the activation of
      TREK-1 K+ channels by masticatory stress contributes to the hyperpolarization of
      PDL fibroblasts.

PMID- 16798871
TI  - The impact of late career job loss on myocardial infarction and stroke: a 10 year
      follow up using the health and retirement survey.
AB  - BACKGROUND: Involuntary job loss is a major life event associated with social,
      economic, behavioural, and health outcomes, for which older workers are at
      elevated risk. OBJECTIVE: To assess the 10 year risk of myocardial infarction
      (MI) and stroke associated with involuntary job loss among workers over 50 years
      of age. METHODS: Analysing data from the nationally representative US Health and
      Retirement Survey (HRS), Cox proportional hazards analysis was used to estimate
      whether workers who suffered involuntary job loss were at higher risk for
      subsequent MI and stroke than individuals who continued to work. The sample
      included 4301 individuals who were employed at the 1992 study baseline. RESULTS:
      Over the 10 year study frame, 582 individuals (13.5% of the sample) experienced
      involuntary job loss. After controlling for established predictors of the
      outcomes, displaced workers had a more than twofold increase in the risk of
      subsequent MI (hazard ratio (HR) = 2.48; 95% confidence interval (CI) = 1.49 to
      4.14) and stroke (HR = 2.43; 95% CI = 1.18 to 4.98) relative to working persons.
      CONCLUSION: Results suggest that the true costs of late career unemployment
      exceed financial deprivation, and include substantial health consequences.
      Physicians who treat individuals who lose jobs as they near retirement should
      consider the loss of employment a potential risk factor for adverse vascular
      health changes. Policy makers and programme planners should also be aware of the
      risks of job loss, so that programmatic interventions can be designed and
      implemented to ease the multiple burdens of joblessness.

PMID- 16798872
TI  - Origins and evolution of the recA/RAD51 gene family: evidence for ancient gene
      duplication and endosymbiotic gene transfer.
AB  - The bacterial recA gene and its eukaryotic homolog RAD51 are important for DNA
      repair, homologous recombination, and genome stability. Members of the recA/RAD51
      family have functions that have differentiated during evolution. However, the
      evolutionary history and relationships of these members remains unclear. Homolog
      searches in prokaryotes and eukaryotes indicated that most eubacteria contain
      only one recA. However, many archaeal species have two recA/RAD51 homologs (RADA
      and RADB), and eukaryotes possess multiple members (RAD51, RAD51B, RAD51C,
      RAD51D, DMC1, XRCC2, XRCC3, and recA). Phylogenetic analyses indicated that the
      recA/RAD51 family can be divided into three subfamilies: (i) RADalpha, with
      highly conserved functions; (ii) RADbeta, with relatively divergent functions;
      and (iii) recA, functioning in eubacteria and eukaryotic organelles. The RADalpha
      and RADbeta subfamilies each contain archaeal and eukaryotic members, suggesting
      that a gene duplication occurred before the archaea/eukaryote split. In the
      RADalpha subfamily, eukaryotic RAD51 and DMC1 genes formed two separate
      monophyletic groups when archaeal RADA genes were used as an outgroup. This
      result suggests that another duplication event occurred in the early stage of
      eukaryotic evolution, producing the DMC1 clade with meiosis-specific genes. The
      RADbeta subfamily has a basal archaeal clade and five eukaryotic clades,
      suggesting that four eukaryotic duplication events occurred before animals and
      plants diverged. The eukaryotic recA genes were detected in plants and protists
      and showed strikingly high levels of sequence similarity to recA genes from
      proteobacteria or cyanobacteria. These results suggest that endosymbiotic
      transfer of recA genes occurred from mitochondria and chloroplasts to nuclear
      genomes of ancestral eukaryotes.

PMID- 16798873
TI  - Os8N3 is a host disease-susceptibility gene for bacterial blight of rice.
AB  - Many bacterial diseases of plants depend on the interaction of type III effector
      genes of the pathogen and disease-susceptibility genes of the host. The host
      susceptibility genes are largely unknown. Here, we show that expression of the
      rice gene Os8N3, a member of the MtN3 gene family from plants and animals, is
      elevated upon infection by Xanthomonas oryzae pv. oryzae strain PXO99(A) and
      depends on the type III effector gene pthXo1. Os8N3 resides near xa13, and
      PXO99(A) failed to induce Os8N3 in rice lines with xa13. Silencing of Os8N3 by
      inhibitory RNA produced plants that were resistant to infection by strain
      PXO99(A) yet remained susceptible to other strains of the pathogen. The effector
      gene avrXa7 from strain PXO86 enabled PXO99(A) compatibility on either xa13- or
      Os8N3-silenced plants. The findings indicate that Os8N3 is a host susceptibility
      gene for bacterial blight targeted by the type III effector PthXo1. The results
      support the hypothesis that X. oryzae pv. oryzae commandeers the regulation of
      otherwise developmentally regulated host genes to induce a state of disease
      susceptibility. Furthermore, the results support a model in which the pathogen
      induces disease susceptibility in a gene-for-gene manner.

PMID- 16798874
TI  - Aspm specifically maintains symmetric proliferative divisions of neuroepithelial
      cells.
AB  - The ASPM (abnormal spindle-like microcephaly-associated) protein has previously
      been implicated in the determination of human cerebral cortical size, but the
      cell biological basis of this regulation has not been studied. Here we
      investigate the role of Aspm in mouse embryonic neuroepithelial (NE) cells, the
      primary stem and progenitor cells of the mammalian brain. Aspm was found to be
      concentrated at mitotic spindle poles of NE cells and to be down-regulated with
      their switch from proliferative to neurogenic divisions. Upon RNA interference in
      telencephalic NE cells, Aspm mRNA is reduced, mitotic spindle poles lack Aspm
      protein, and the cleavage plane of NE cells is less frequently oriented
      perpendicular to the ventricular surface of the neuroepithelium. The alteration
      in the cleavage plane orientation of NE cells increases the probability that
      these highly polarized cells undergo asymmetric division, i.e., that apical
      plasma membrane is inherited by only one of the daughter cells. Concomitant with
      the resulting increase in abventricular cells in the ventricular zone, a larger
      proportion of NE cell progeny is found in the neuronal layer, implying a
      reduction in the number of NE progenitor cells upon Aspm knock-down relative to
      control. Our results demonstrate that Aspm is crucial for maintaining a cleavage
      plane orientation that allows symmetric, proliferative divisions of NE cells
      during brain development. These data provide a cell biological explanation of the
      primary microcephaly observed in humans with mutations in ASPM, which also has
      implications for the evolution of mammalian brains.

PMID- 16798875
TI  - Mating-responsive genes in reproductive tissues of female Drosophila
      melanogaster.
AB  - Male-derived accessory gland proteins that are transferred to females during
      mating have profound effects on female reproductive physiology including
      increased ovulation, mating inhibition, and effects on sperm utilization and
      storage. The extreme rates of evolution seen in accessory gland proteins may be
      driven by sperm competition and sexual conflict, processes that may ultimately
      drive complex interactions between female- and male-derived molecules and sperm.
      However, little is known of how gene expression in female reproductive tissues
      changes in response to the presence of male molecules and sperm. To characterize
      this response, we conducted parallel genomic and proteomic analyses of gene
      expression in the reproductive tract of 3-day-old unmated and mated female
      Drosophila melanogaster. Using DNA microarrays, we identified 539 transcripts
      that are differentially expressed in unmated vs. mated females and revealed a
      striking peak in differential expression at 6 h postmating and a marked shift
      from primarily down-regulated to primarily up-regulated transcripts within 3 h
      after mating. Combining two-dimensional gel electrophoresis and liquid
      chromatography mass spectrometry analyses, we identified 84 differentially
      expressed proteins at 3 h postmating, including proteins that appeared to undergo
      posttranslational modification. Together, our observations define transcriptional
      and translational response to mating within the female reproductive tract and
      suggest a bimodal model of postmating gene expression initially correlated with
      mating and the final stages of female reproductive tract maturation and later
      with the declining presence of male reproductive molecules and with sperm
      maintenance and utilization.

PMID- 16798876
TI  - TNF-alpha inhibits asbestos-induced cytotoxicity via a NF-kappaB-dependent
      pathway, a possible mechanism for asbestos-induced oncogenesis.
AB  - Asbestos is the main cause of human malignant mesothelioma (MM). In vivo,
      macrophages phagocytize asbestos and, in response, release TNF-alpha and other
      cytokines that contribute to carcinogenesis through unknown mechanisms. In vitro,
      asbestos does not induce transformation of primary human mesothelial cells (HM);
      instead, asbestos is very cytotoxic to HM, causing extensive cell death. This
      finding raised an apparent paradox: How can asbestos cause MM if HM exposed to
      asbestos die? We found that asbestos induced the secretion of TNF-alpha and the
      expression of TNF-alpha receptor I in HM. Treatment of HM with TNF-alpha
      significantly reduced asbestos cytotoxicity. Through numerous technical
      approaches, including chemical inhibitors and small interfering RNA strategies,
      we demonstrate that, in HM, TNF-alpha activates NF-kappaB and that NF-kappaB
      activation leads to HM survival and resistance to the cytotoxic effects of
      asbestos. Our data show a critical role for TNF-alpha and NF-kappaB signaling in
      mediating HM responses to asbestos. TNF-alpha signaling through NF-kappaB
      dependent mechanisms increases the percent of HM that survives asbestos exposure,
      thus increasing the pool of asbestos-damaged HM that are susceptible to malignant
      transformation. Cytogenetics supported this hypothesis, showing only rare,
      aberrant metaphases in HM exposed to asbestos and an increased mitotic rate with
      fewer irregular metaphases in HM exposed to both TNF-alpha and asbestos. Our
      findings provide a mechanistic rationale for the paradoxical inability of
      asbestos to transform HM in vitro, elucidate and underscore the role of TNF-alpha
      in asbestos pathogenesis in humans, and identify potential molecular targets for
      anti-MM prevention and therapy.

PMID- 16798877
TI  - Aphid alarm pheromone produced by transgenic plants affects aphid and parasitoid
      behavior.
AB  - The alarm pheromone for many species of aphids, which causes dispersion in
      response to attack by predators or parasitoids, consists of the sesquiterpene (E)
      beta-farnesene (Ebetaf). We used high levels of expression in Arabidopsis
      thaliana plants of an Ebetaf synthase gene cloned from Mentha x piperita to cause
      emission of pure Ebetaf. These plants elicited potent effects on behavior of the
      aphid Myzus persicae (alarm and repellent responses) and its parasitoid
      Diaeretiella rapae (an arrestant response). Here, we report the transformation of
      a plant to produce an insect pheromone and demonstrate that the resulting
      emission affects behavioral responses at two trophic levels.

PMID- 16798878
TI  - Nonhepatic origin of notothenioid antifreeze reveals pancreatic synthesis as
      common mechanism in polar fish freezing avoidance.
AB  - Phylogenetically diverse polar and subpolar marine teleost fishes have evolved
      antifreeze proteins (AFPs) or antifreeze glycoproteins (AFGPs) to avoid
      inoculative freezing by internalized ice. For over three decades since the first
      fish antifreeze (AF) protein was discovered, many studies of teleost freezing
      avoidance showed hepatic AF synthesis and distribution within the circulation as
      pivotal in preventing the blood, and therefore the fish, from freezing. We have
      uncovered an important twist to this long-held paradigm: the complete absence of
      liver synthesis of AFGPs in any life stage of the Antarctic notothenioids,
      indicating that the liver plays no role in the freezing avoidance in these
      fishes. Instead, we found the exocrine pancreas to be the major site of AFGP
      synthesis and secretion in all life stages, and that pancreatic AFGPs enter the
      intestinal lumen via the pancreatic duct to prevent ingested ice from nucleating
      the hyposmotic intestinal fluids. AFGPs appear to remain undegraded in the
      intestinal milieu, and the composition and relative abundance of intestinal AFGP
      isoforms are nearly identical to serum AFGPs. Thus, the reabsorption of intact
      pancreas-derived intestinal AFGPs, and not the liver, is the likely source of
      circulatory AFGPs in notothenioid fishes. We examined diverse northern fish taxa
      and Antarctic eelpouts with hepatic synthesis of bloodborne AF and found that
      they also express secreted pancreatic AF of their respective types. The
      evolutionary convergence of this functional physiology underscores the hitherto
      largely unrecognized importance of intestinal freezing prevention in polar
      teleost freezing avoidance, especially in the chronically icy Antarctic waters.

PMID- 16798879
TI  - A burst of auxilin recruitment determines the onset of clathrin-coated vesicle
      uncoating.
AB  - Clathrin-coated pits assemble on a membrane and pinch off as coated vesicles. The
      released vesicles then rapidly lose their clathrin coats in a process mediated by
      the ATPase Hsc70, recruited by auxilin, a J-domain-containing cofactor. How is
      the uncoating process regulated? We find that during coat assembly small and
      variable amounts of auxilin are recruited transiently but that a much larger
      burst of association occurs after the peak of dynamin signal, during the
      transition between membrane constriction and vesicle budding. We show that the
      auxilin burst depends on domains of the protein likely to interact with lipid
      head groups. We conclude that the timing of auxilin recruitment determines the
      onset of uncoating. We propose that, when a diffusion barrier is established at
      the constricting neck of a fully formed coated pit and immediately after vesicle
      budding, accumulation of a specific lipid can recruit sufficient auxilin
      molecules to trigger uncoating.

PMID- 16798880
TI  - Exceptional chemical and thermal stability of zeolitic imidazolate frameworks.
AB  - Twelve zeolitic imidazolate frameworks (ZIFs; termed ZIF-1 to -12) have been
      synthesized as crystals by copolymerization of either Zn(II) (ZIF-1 to -4, -6 to 
      8, and -10 to -11) or Co(II) (ZIF-9 and -12) with imidazolate-type links. The ZIF
      crystal structures are based on the nets of seven distinct aluminosilicate
      zeolites: tetrahedral Si(Al) and the bridging O are replaced with transition
      metal ion and imidazolate link, respectively. In addition, one example of mixed
      coordination imidazolate of Zn(II) and In(III) (ZIF-5) based on the garnet net is
      reported. Study of the gas adsorption and thermal and chemical stability of two
      prototypical members, ZIF-8 and -11, demonstrated their permanent porosity
      (Langmuir surface area = 1,810 m(2)/g), high thermal stability (up to 550 degrees
      C), and remarkable chemical resistance to boiling alkaline water and organic
      solvents.

PMID- 16798881
TI  - Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic
      DNA replication fork helicase.
AB  - The protein Cdc45 plays a critical but poorly understood role in the initiation
      and elongation stages of eukaryotic DNA replication. To study Cdc45's function in
      DNA replication, we purified Cdc45 protein from Drosophila embryo extracts by a
      combination of traditional and immunoaffinity chromatography steps and found that
      the protein exists in a stable, high-molecular-weight complex with the Mcm2-7
      hexamer and the GINS tetramer. The purified Cdc45/Mcm2-7/GINS complex is
      associated with an active ATP-dependent DNA helicase function. RNA interference
      knock-down experiments targeting the GINS and Cdc45 components establish that the
      proteins are required for the S phase transition in Drosophila cells. The data
      suggest that this complex forms the core helicase machinery for eukaryotic DNA
      replication.

PMID- 16798882
TI  - Folding of Cu/Zn superoxide dismutase suggests structural hotspots for gain of
      neurotoxic function in ALS: parallels to precursors in amyloid disease.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to
      misfolding of the ubiquitous enzyme Cu/Zn superoxide dismutase (SOD). In contrast
      to other protein-misfolding disorders with similar neuropathogenesis, ALS is not
      always associated with the in vivo deposition of protein aggregates. Thus, under
      the assumption that all protein-misfolding disorders share at primary level a
      similar disease mechanism, ALS constitutes an interesting disease model for
      identifying the yet-mysterious precursor states from which the cytotoxic pathway
      emerges. In this study, we have mapped out the conformational repertoire of the
      apoSOD monomer through analysis of its folding behavior. The results allow us to
      target the regions of the SOD structure that are most susceptible to unfolding
      locally under physiological conditions, leading to the exposure of structurally
      promiscuous interfaces that are normally hidden in the protein's interior. The
      structure of this putative ALS precursor is strikingly similar to those
      implicated in amyloid disease.

PMID- 16798883
TI  - B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with
      cancer progression and survival.
AB  - B7-H4 is a recently described B7 family coregulatory ligand that has been
      implicated as an inhibitor of T cell-mediated immunity. Although expression of B7
      H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also
      been reported in several human malignancies. To date, associations of B7-H4 with
      clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4
      expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC)
      patients treated with nephrectomy between 2000 and 2003 and performed correlative
      outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4
      staining and that tumor cell B7-H4 expression was associated with adverse
      clinical and pathologic features, including constitutional symptoms, tumor
      necrosis, and advanced tumor size, stage, and grade. Patients with tumors
      expressing B7-H4 were also three times more likely to die from RCC compared with
      patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P
      = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature
      endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue
      vessels exhibited endothelial B7-H4 staining. Based on these findings, we
      conclude that B7-H4 has the potential to be a useful prognostic marker for
      patients with RCC. In addition, B7-H4 represents a target for attacking tumor
      cells as well as tumor neovasculature to facilitate immunotherapeutic treatment
      of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both
      B7-H4 and B7-H1 are at an even greater risk of death from RCC.

PMID- 16798884
TI  - Deletion of the neuropeptide Y (NPY) Y1 receptor gene reveals a regulatory role
      of NPY on catecholamine synthesis and secretion.
AB  - The contribution of neuropeptide Y (NPY), deriving from adrenal medulla, to the
      adrenosympathetic tone is unknown. We found that in response to NPY, primary
      cultures of mouse adrenal chromaffin cells secreted catecholamine, and that this
      effect was abolished in cultures from NPY Y(1) receptor knockout mice (Y(1)-/-).
      Compared with wild-type mice (Y(1)+/+), the adrenal content and constitutive
      release of catecholamine were increased in chromaffin cells from Y(1)-/- mice. In
      resting animals, catecholamine plasma concentrations were higher in Y(1)-/- mice.
      Comparing the adrenal glands of both genotypes, no differences were observed in
      the area of the medulla, cortex, and X zone. The high turnover of adrenal
      catecholamine in Y(1)-/- mice was explained by the enhancement of tyrosine
      hydroxylase (TH) activity, although no change in the affinity of the enzyme was
      observed. The molecular interaction between the Y(1) receptor and TH was
      demonstrated by the fact that NPY markedly inhibited the forskolin-induced
      luciferin activity in Y(1) receptor-expressing SK-N-MC cells transfected with a
      TH promoter sequence. We propose that NPY controls the release and synthesis of
      catecholamine from the adrenal medulla and consequently contributes to the
      sympathoadrenal tone.

PMID- 16798886
TI  - MicroRNA-targeted and small interfering RNA-mediated mRNA degradation is
      regulated by argonaute, dicer, and RNA-dependent RNA polymerase in Arabidopsis.
AB  - ARGONAUTE1 (AGO1) of Arabidopsis thaliana mediates the cleavage of microRNA
      (miRNA)-targeted mRNAs, and it has also been implicated in the
      posttranscriptional silencing of transgenes and the maintenance of chromatin
      structure. Mutations in AGO1 severely disrupt plant development, indicating that
      miRNA function and possibly other aspects of RNA interference are essential for
      maintaining normal patterns of gene expression. Using microarrays, we found that
      1 to 6% of genes display significant expression changes in several alleles of
      ago1 at multiple developmental stages, with the majority showing higher levels.
      Several classes of known miRNA targets increased markedly in ago1, whereas others
      showed little or no change. Cleavage of mRNAs within miRNA-homologous sites was
      reduced but not abolished in an ago1 -null background, indicating that redundant
      slicer activity exists in Arabidopsis. Small interfering RNAs and larger 30- to
      60-nucleotide RNA fragments corresponding to highly upregulated miRNA target
      genes accumulated in wild-type plants but not in ago1, the RNA-dependent RNA
      polymerase mutants rdr2 and rdr6, or the Dicer-like mutants dcl1 and dcl3. Both
      sense and antisense RNAs corresponding to these miRNA targets accumulated in the
      ago1 and dcl1 backgrounds. These results indicate that a subset of endogenous
      mRNA targets of RNA interference may be regulated through a mechanism of second
      strand RNA synthesis and degradation initiated by or in addition to miRNA
      mediated cleavage.

PMID- 16798887
TI  - KNAT6: an Arabidopsis homeobox gene involved in meristem activity and organ
      separation.
AB  - The homeobox gene family plays a crucial role during the development of
      multicellular organisms. The KNOTTED-like genes from Arabidopsis thaliana (KNAT6
      and KNAT2) are close relatives of the meristematic genes SHOOT MERISTEMLESS (STM)
      and BREVIPEDICELLUS, but their function is not currently known. To investigate
      their role, we identified null alleles of KNAT6 and KNAT2. We demonstrate that
      KNAT6 contributes redundantly with STM to the maintenance of the shoot apical
      meristem (SAM) and organ separation. Consistent with this role, the expression
      domain of KNAT6 in the SAM marks the boundaries between the SAM and cotyledons.
      The lack of meristematic activity in the knat6 stm-2 double mutant and the fusion
      of cotyledons were linked to the modulation of CUP-SHAPED COTYLEDON (CUC)
      activity. During embryogenesis, KNAT6 is expressed later than STM and CUC. In
      agreement with this fact, CUC1 and CUC2 were redundantly required for KNAT6
      expression. These data provide the basis for a model in which KNAT6 contributes
      to SAM maintenance and boundary establishment in the embryo via the STM/CUC
      pathway. KNAT2, although the closest related member of the family to KNAT6, did
      not have such a function.

PMID- 16798888
TI  - Proteomic analysis of the eyespot of Chlamydomonas reinhardtii provides novel
      insights into its components and tactic movements.
AB  - Flagellate green algae have developed a visual system, the eyespot apparatus,
      which allows the cell to phototax. To further understand the molecular
      organization of the eyespot apparatus and the phototactic movement that is
      controlled by light and the circadian clock, a detailed understanding of all
      components of the eyespot apparatus is needed. We developed a procedure to purify
      the eyespot apparatus from the green model alga Chlamydomonas reinhardtii. Its
      proteomic analysis resulted in the identification of 202 different proteins with
      at least two different peptides (984 in total). These data provide new insights
      into structural components of the eyespot apparatus, photoreceptors, retina(l)
      related proteins, members of putative signaling pathways for phototaxis and
      chemotaxis, and metabolic pathways within an algal visual system. In addition, we
      have performed a functional analysis of one of the identified putative components
      of the phototactic signaling pathway, casein kinase 1 (CK1). CK1 is also present
      in the flagella and thus is a promising candidate for controlling behavioral
      responses to light. We demonstrate that silencing CK1 by RNA interference reduces
      its level in both flagella and eyespot. In addition, we show that silencing of
      CK1 results in severe disturbances in hatching, flagellum formation, and
      circadian control of phototaxis.

PMID- 16798891
TI  - Role of transrectal ultrasonography in the prediction of prostate cancer:
      artificial neural network analysis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance
      of an artificial neural network (ANN) model with and without transrectal
      ultrasonographic (TRUS) data. METHODS: Six hundred eighty-four consecutive
      patients who had undergone TRUS-guided prostate biopsy from May 2003 to January
      2005 were enrolled. We constructed 2 ANN models. One (ANN_1) incorporated patient
      age, digital rectal examination findings, prostate-specific antigen (PSA) level,
      PSA density, transitional zone volume, and PSA density in the transitional zone
      as input data, whereas the other (ANN_2) was constructed with the above and TRUS
      findings as input data. The performances of these 2 ANN models according to PSA
      levels (group A, 0-4 ng/mL; group B, 4-10 ng/mL; and group C, >10 ng/mL) were
      evaluated using receiver operating characteristic analysis. RESULTS: Of the 684
      patients who underwent prostate biopsy, 214 (31.3%) were confirmed to have
      prostate cancer; of 137 patients with positive digital rectal examination
      results, 60 (43.8%) were confirmed to have prostate cancer; and of 131 patients
      with positive TRUS findings, 93 (71%) were confirmed to have prostate cancer. In
      groups A, B, and C, the AUCs for ANN_1 were 0.738, 0.753, and 0.774,
      respectively; the AUCs for ANN_2 were 0.859, 0.797, and 0.894. In all groups,
      ANN_2 showed better accuracy than ANN_1 (P < .05). CONCLUSIONS: According to
      receiver operating characteristic analysis, ANN with TRUS findings was found to
      be more accurate than ANN without. We conclude that TRUS findings should be
      included as an input data component in ANN models used to diagnose prostate
      cancer.

PMID- 16798885
TI  - A genome-wide survey of R gene polymorphisms in Arabidopsis.
AB  - We used polymorphism analysis to study the evolutionary dynamics of 27 disease
      resistance (R) genes by resequencing the leucine-rich repeat (LRR) region in 96
      Arabidopsis thaliana accessions. We compared single nucleotide polymorphisms
      (SNPs) in these R genes to an empirical distribution of SNP in the same sample
      based on 876 fragments selected to sample the entire genome. LRR regions are
      highly polymorphic for protein variants but not for synonymous changes,
      suggesting that they generate many alleles maintained for short time periods.
      Recombination is also relatively common and important for generating protein
      variants. Although none of the genes is nearly as polymorphic as RPP13, a locus
      previously shown to have strong signatures of balancing selection, seven genes
      show weaker indications of balancing selection. Five R genes are relatively
      invariant, indicating young alleles, but all contain segregating protein
      variants. Polymorphism analysis in neighboring fragments yielded inconclusive
      evidence for recent selective sweeps at these loci. In addition, few alleles are
      candidates for rapid increases in frequency expected under directional selection.
      Haplotype sharing analysis revealed significant underrepresentation of R gene
      alleles with extended haplotypes compared with 1102 random genomic fragments.
      Lack of convincing evidence for directional selection or selective sweeps argues
      against an arms race driving R gene evolution. Instead, the data support
      transient or frequency-dependent selection maintaining protein variants at a
      locus for variable time periods.

PMID- 16798892
TI  - Role of transrectal ultrasonography in the evaluation of azoospermic men with low
      volume ejaculate.
AB  - OBJECTIVE: The purpose of this prospective study was to evaluate the incidence of
      distal ejaculatory system defects with transrectal ultrasonography (TRUS) among
      patients evaluated for azoospermia. METHODS: Forty-two patients with low-volume
      ejaculate and azoospermia were evaluated by physical examination, serum follicle
      stimulating hormone and luteinizing hormone level determination, karyotyping,
      selective screening for cystic fibrosis mutations, and TRUS. RESULTS: On physical
      examination, in 29 patients (69%), either 1 (12 patients) or both (17 patients)
      of the vasa deferentia could not be palpated. In the group of 17 patients with
      bilateral involvement of the vasa deferentia, the ultrasonographic imaging
      universally showed bilateral absence or hypoplasia of the seminal vesicles with
      bilateral agenesis of the vasa deferentia and nonvisualization of both
      ejaculatory ducts. In the patients with a unilateral abnormality on physical
      examination, the ultrasonographic imaging showed absence of the ipsilateral
      seminal vesicle in 7 patients and the hypoplastic seminal vesicle in 5. In the
      group of 13 patients with normal physical examination findings, a variety of
      obstructive causes were diagnosed by TRUS examination. CONCLUSIONS: According to
      this study, TRUS appears to be a sensitive method for evaluating the anatomy of
      the distal ejaculatory system. Its safety and low costs make it a good
      alternative to the other invasive and expensive methods.

PMID- 16798889
TI  - AGL80 is required for central cell and endosperm development in Arabidopsis.
AB  - During plant reproduction, the central cell of the female gametophyte becomes
      fertilized to produce the endosperm, a storage tissue that nourishes the
      developing embryo within the seed. The molecular mechanisms controlling the
      specification and differentiation of the central cell are poorly understood. We
      identified a female gametophyte mutant in Arabidopsis thaliana, fem111, that is
      affected in central cell development. In fem111 female gametophytes, the central
      cell's nucleolus and vacuole fail to mature properly. In addition, endosperm
      development is not initiated after fertilization of fem111 female gametophytes.
      fem111 contains a T-DNA insertion in AGAMOUS-LIKE80 (AGL80). FEM111/AGL80 is a
      member of the MADS box family of genes that likely encode transcription factors.
      An AGL80-green fluorescent protein fusion protein is localized to the nucleus.
      Within the ovule and seed, FEM111/AGL80 is expressed exclusively in the central
      cell and uncellularized endosperm. FEM111/AGL80 expression is also detected in
      roots, leaves, floral stems, anthers, and young flowers by real-time RT-PCR.
      FEM111/AGL80 is required for the expression of two central cell-expressed genes,
      DEMETER and DD46, but not for a third central cell-expressed gene, FERTILIZATION
      INDEPENDENT SEED2. Together, these data suggest that FEM111/AGL80 functions as a
      transcription factor within the central cell gene regulatory network and controls
      the expression of downstream genes required for central cell development and
      function.

PMID- 16798893
TI  - Effect of premicturitional bladder volume on the accuracy of postvoid residual
      urine volume measurement by transabdominal ultrasonography: rate of bladder
      fullness is of great importance for preventing false-positive residue diagnosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of
      premicturitional bladder volume (V1) on postvoid residual urine volume (V2)
      measurements and to assess the ideal V1 for an accurate V2 determination.
      METHODS: Twenty-five healthy men without any urinary symptoms constituted the
      study group. Measurements by transabdominal ultrasonography for V1 and V2 were
      performed for each subject at 3 different phases, each of which was preceded by
      oral intake of 1000 mL of water and accompanied by "mild," "moderate," and
      "severe" sensations of micturition, respectively. RESULTS: Mean +/- SD V1 and V2
      during the first, second, and third phases were 117.7 +/- 70.3 and 1 +/- 1, 356.2
      +/- 112.3 and 11.5 +/- 12 and 639.6 +/- 171.8 and 58.8 +/- 35.2 mL, respectively.
      With 50 mL as the cutoff value for a pathologic V2, 15 (60%) men had V2 in the
      third phase exceeding this value, whereas the same rate was calculated as 0% for
      either of the first 2 phases. No patient with V1 of less than 540 mL had V2 of
      greater than 50 mL. CONCLUSIONS: Postvoid residual urine volume measurements with
      an uncomfortably full bladder result in high false-positive postmicturitional
      residue values even in healthy young men. We strongly advise that V1 measurements
      of the bladder be performed before V2 measurements and that V2 not be measured if
      V1 is greater than 540 mL.

PMID- 16798894
TI  - Unilateral idiopathic hydrocele has a substantial effect on the ipsilateral
      testicular geometry and resistivity indices.
AB  - OBJECTIVE: The purpose of this study was to determine whether hydrocele has any
      effect on the volume and shape of the ipsilateral testis and can be implicated as
      a cause of testicular ischemia. METHODS: Group 1 consisted of 23 patients with
      unilateral idiopathic hydrocele, whereas 30 healthy men constituted group 2. All
      patients underwent scrotal ultrasonography by which testicular dimensions in
      craniocaudal (D(cc)), anteroposterior (D(ap)), and mediolateral axes were
      measured, followed by calculation of the D(cc)/D(ap) ratio and testicular volume.
      By color Doppler analysis, the resistivity index of the subcapsular artery
      (RI(sc)) and the resistivity index of the intratesticular artery were determined.
      RESULTS: The mean D(cc)/D(ap) ratio +/- SD for group 1 was 1.7 +/- 0.3 (range,
      1.1-2.3), significantly lower than that of group 2, which was 1.9 +/- 0.3 (range,
      1.3-2.2) (P = .028). Mean testicular volume values of subjects having hydrocele
      for more than and less than 6 months were 13.4 +/- 7.3 and 22.5 +/- 5.1 cm3,
      respectively; the difference between the subgroups was significant (P = .003).
      For the ipsilateral testis, mean RI(sc) values were 0.70 +/- 0.06 (range, 0.60
      0.80) in group 1 and 0.65 +/- 0.06 (range, 0.59-0.83) in group 2. The mean RI(sc)
      was significantly higher in group 1 (P = .006). CONCLUSIONS: Unilateral
      idiopathic hydrocele has a tendency for rounding rather than flattening the
      ipsilateral testis as well as elevating the RI(sc) on the affected side. To the
      best of our knowledge, no strict spectral Doppler analysis criteria have been
      proposed for testicular ischemia yet. Therefore, the impact of the difference of
      the RI(sc) should raise the suspicion for ischemia, and further research is
      needed to elucidate any effect on spermatogenesis.

PMID- 16798890
TI  - Endocytosis is essential for pathogenic development in the corn smut fungus
      Ustilago maydis.
AB  - It is well established that polarized exocytosis is essential for fungal
      virulence. By contrast, the contribution of endocytosis is unknown. We made use
      of a temperature-sensitive mutant in the endosomal target soluble N
      ethylmaleimide-sensitive factor attachment protein receptor Yup1 and demonstrate
      that endocytosis in Ustilago maydis is essential for the initial steps of
      pathogenic development, including pheromone perception and cell-cell fusion.
      Furthermore, spore formation and germination were drastically reduced, whereas
      colonization of the plant was only slightly inhibited. The function of
      endocytosis in the recognition of mating pheromone through the G protein-coupled
      pheromone receptor Pra1 was analyzed in greater detail. Biologically active Pra1
      green fluorescent protein localizes to the plasma membrane and is constitutively
      endocytosed. Yup1(ts) mutants that are blocked in the fusion of endocytic
      transport vesicles with early endosomes are impaired in pheromone perception and
      conjugation hyphae formation. This is attributable to an accumulation of Pra1
      carrying endocytic vesicles in the cytoplasm and the depletion of the receptor
      from the membrane. Consistently, strong Pra1 expression rescues the signaling
      defects in endocytosis mutants, but subsequent cell fusion is still impaired.
      Thus, we conclude that endocytosis is essential for recognition of the partner at
      the beginning of the pathogenic program but has additional roles in mating as
      well as spore formation and germination.

PMID- 16798895
TI  - Contribution of tissue harmonic imaging and frequency compound imaging in
      interventional breast sonography.
AB  - OBJECTIVE: The purpose of this study was to retrospectively compare conventional
      imaging, frequency compound imaging (CI), and tissue harmonic imaging (THI) in
      interventional breast sonography. METHODS: Institutional Review Board approval
      and patient informed consent were not required. The authors reviewed 104
      sonographically guided breast procedures in 83 patients. For each biopsy, 4
      images obtained with conventional imaging, frequency CI at 10 and 14 MHz (CI10
      and CI14), and THI were graded independently by 2 radiologists for lesion
      conspicuity, needle conspicuity, lesion and needle conspicuity, and overall image
      quality. Frequency CI at 10 MHz, CI14, and THI were compared with conventional
      imaging. Different clinical scenarios (fatty versus glandular background, fine
      needle versus core needle, and oblique versus horizontal needle direction) were
      evaluated. RESULTS: Statistical analysis showed that for overall image quality,
      CI10 was the best setting (odds ratios [OR], 3.67 and 7.48). For lesion
      conspicuity, CI14 (OR, 3.55) and THI (OR, 1.77) improved lesion visibility in a
      fatty background, whereas THI (OR, 0.26) was very limited in a glandular
      background. For needle conspicuity, no setting was better than conventional,
      whereas THI was the least valuable setting (OR, 0.011 and 0.049). For lesion and
      needle conspicuity, CI10 showed significantly better results than conventional
      for a dense background (P = .0268 and .4028; OR, 2.435 and 1.383) with 1
      reviewer, whereas THI was the least valuable setting (OR, 0.014 and 0.042).
      CONCLUSIONS: Conventional imaging provided the best assessment of lesion and
      needle conspicuity. Frequency compounding is a useful setting for dense breast
      and for fine-needle aspiration. Tissue harmonic imaging has a role in the
      visualization of a lesion against a fatty background but is of limited value in
      needle visualization.

PMID- 16798896
TI  - Sonographic septation in lymphocyte-rich exudative pleural effusions: a useful
      diagnostic predictor for tuberculosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of the sonographic
      features of lymphocyte-rich exudative pleural effusions in the differential
      diagnosis of tuberculosis and lung cancer in an area with a high incidence of
      tuberculosis. METHODS: Medical records of patients undergoing chest sonography
      between January 2003 and June 2005 (30 months) were reviewed retrospectively. The
      enrolled patients included 73 with lung cancer-related pleural effusions and 93
      with tuberculous pleural effusions. The sonographic appearances of the pleural
      effusions were defined in terms of 4 patterns: anechoic, homogeneously echogenic,
      complex septated, and complex nonseptated. RESULTS: Among the 73 lung cancer
      related pleural effusions, there were sonographic appearances of an anechoic
      pattern in 11% (8/73), a complex septated pattern in 4% (3/73), and a complex
      nonseptated pattern in 85% (62/73). In 93 tuberculous pleural effusions, there
      were sonographic appearances of an anechoic pattern in 12% (11/93), a complex
      septated pattern in 47% (44/93), and a complex non-septated pattern in 41%
      (38/93). Apparently, a complex septated pattern in the sonographic appearance of
      lymphocyte-rich pleural effusions is a useful diagnostic predictor for
      differentiating tuberculosis from lung cancer (95% confidence interval, -0.57 to 
      0.29). If we define the complex septated pattern in the sonographic appearance of
      lymphocyte-rich exudative pleural effusions as a predictor for tuberculous
      pleural effusions, we can achieve sensitivity, specificity, positive predictive
      value, negative predictive value, and positive likelihood ratio values of 47%,
      96%, 94%, 59%, and 12, respectively. CONCLUSIONS: A complex septated pattern in
      the sonographic appearance is a useful predictor of tuberculosis in lymphocyte
      rich exudative pleural effusions.

PMID- 16798897
TI  - Sonography of intramuscular myxomas: the bright rim and bright cap signs.
AB  - OBJECTIVE: The objective of this study was to retrospectively review sonographic
      images of pathologically proven soft tissue myxomas to determine whether a
      sonographic correlate to the bright rim and bright cap signs described in the
      magnetic resonance imaging literature is present. METHODS: The study group
      consisted of 6 patients with pathologically proven soft tissue myxomas (1 man and
      5 women; age range, 41-72 years; mean, 56.5 years). The available sonographic
      images for each subject were retrospectively reviewed by 2 authors (L.F. and
      K.F.), with agreement reached by consensus. Among other findings, images were
      also reviewed for a peripheral rim of increased echogenicity (termed the "bright
      rim sign") and for the presence of a triangular hyperechoic area adjacent to at
      least one of the poles of the mass (termed the "bright cap sign"). RESULTS: The
      bright rim and bright cap signs were seen in 5 (83%) of the 6 myxomas. The single
      case without the bright cap sign was not the same case as the one lacking the
      bright rim sign. CONCLUSIONS: The sonographic bright rim and bright cap signs
      were associated with 5 (83%) of the 6 intramuscular myxomas. These findings
      correlate with their magnetic resonance imaging equivalents, which are well
      documented in the literature, due to muscle atrophy and adjacent fatty
      infiltration. Recognition of these features may assist in a more accurate
      sonographic diagnosis before biopsy.

PMID- 16798899
TI  - Microvascular behavior and effects of sonazoid microbubbles in the cremaster
      muscle of rats after local administration.
AB  - OBJECTIVE: The purpose of this study was to observe Sonazoid perfluorobutane
      microbubbles (GE Healthcare, Amersham, Buckinghamshire, England) in and their
      effects on the cremaster capillary microcirculation of rats. METHODS: Sonazoid
      (0.3 x 10(9) microbubbles in 0.5 mL) was observed by intravital microscopy in the
      cremaster muscle after retrograde administration into the femoral artery of 6
      animals. Microbubble and microvessel diameters and blood flow velocities and the
      overall mean and SD of the 1-minute volume flow through the microscopic field
      were calculated from the 2 to 4 capillaries observed in the field of each animal.
      Fluorescein isothiocyanate-dextran leakage was used to assess extravasation after
      microbubble passage. RESULTS: seconds, respectively, before they were released
      and capillary flow normalized. No microbubble size changes, damming, or
      coalescence of bubbles and no changes in microvessel diameter or microvascular
      blood flow velocities, volume flow, or perfusion heterogeneity occurred during or
      after the passage of the Sonazoid suspension or the vehicle. No fluorescein
      isothiocyanate-dextran leakage was observed. CONCLUSIONS: The passage of Sonazoid
      bubbles at concentrations higher than those expected after intravenous
      administration of the Sonazoid did not durably impair microvascular perfusion,
      structural integrity, or macromolecular retention in the rat cremaster muscle.
      The duration of discrete capillary obstructions was short and in all cases
      comparable with that of naturally occurring leukocyte plugging.

PMID- 16798898
TI  - Superthreshold behavior of ultrasound-induced lung hemorrhage in adult rats: role
      of pulse repetition frequency and pulse duration.
AB  - OBJECTIVE: The purpose of this study was to enhance the findings of an earlier
      ultrasound-induced lung hemorrhage study (Ultrasound Med Biol 2003; 29:1625-1634)
      that estimated pressure thresholds as a function of pulse duration (PD: 1.3, 4.4,
      8.2, and 11.6 micros; 2.8 MHz; 10-s exposure duration [ED]; 1-kHz pulse
      repetition frequency [PRF]). In this study, the roles of PRF and PD were
      evaluated at 5.9 MPa, the peak rarefactional pressure threshold near that of the
      ED50 estimate previously determined. METHODS: A 4 x 4 factorial design study
      (PRF: 50, 170, 500, and 1700 Hz; PD: 1.3, 4.4, 8.2, and 11.6 mus) was conducted
      (2.8 MHz; 10-s ED). Sprague Dawley rats (n = 175) were divided into 16 exposure
      groups (10 rats per group) and 1 sham group (15 rats); no lesions were produced
      in the sham group. Logistic regression analysis evaluated significance of effects
      for lesion occurrence, and Gaussian tobit analysis evaluated significance for
      lesion depth and surface area. RESULTS: For lesion occurrence and sizes, the main
      effect of PRF was not significant. The interaction term, PRF x PD, was highly
      significant, indicating a strong positive dependence of lesion occurrence on the
      duty factor. The main effect of PD was almost significant (P = .052) and thus was
      included in the analysis model for a better fit. CONCLUSIONS: Compared with the
      findings from a PRF x ED factorial study (J Ultrasound Med 2005; 24:339-348), a
      function that considers PRF, PD, and ED might yield a sensitive indicator for
      consideration of a modified mechanical index, at least for the lung.

PMID- 16798900
TI  - Experimental study of acute organophosphorus compound poisoning in rabbit kidneys
      by ultrasonic tissue characterization.
AB  - OBJECTIVE: The purpose of this study was to investigate the value of integrated
      backscatter (IBS) of kidneys in acute organophosphorus compound poisoning in
      rabbits. METHODS: Eighteen rabbits were poisoned by dimethyl dichlorovinyl
      phosphate to establish animal models. Sonographic examinations were performed
      before (T0) and after (T1-T9) the rabbits were poisoned. The echo and size of
      kidneys were evaluated by 2-dimensional gray scale sonography. Changes of the
      renal cortex and medulla were analyzed quantitatively with IBS. RESULTS: No
      change of the cortex echo was found before and after poisoning. A significant
      change of the volume of kidneys on both sides began at T6 compared with that at
      T0 (P < .05). A significant change of renal length on both sides began at T7
      compared with that at T0 (P < .05). The volume change was earlier than that of
      length. A significant change in IBS% of the renal cortex began at T5 compared
      with that at T0 (P < .05), whereas a significant change in IBS% of the renal
      medulla began at T6 compared with that at T(0) (P < .05). The change in IBS% of
      the renal cortex was earlier. CONCLUSIONS: More useful information provided by
      IBS% has been found in acute organophosphorus compound poisoning in rabbits.

PMID- 16798901
TI  - Application of power Doppler vocal fremitus sonography in breast lesions.
AB  - OBJECTIVE: The purpose of this study was to illustrate the method and use of
      power Doppler vocal fremitus (PDVF) sonography in the detection and diagnosis of
      breast lesions. METHODS: One case was evaluated by various sonographic parameters
      and equipment to determine how the VF images were affected. Cases illustrative of
      a broad range of breast conditions were also collected. Each image pair consisted
      of B-mode and VF images to maintain an identical projection and to illustrate the
      influence of PDVF sonography. RESULTS: With B-mode and PDVF sonography, we
      evaluated and compared various breast conditions, including normal anatomic
      structures and abnormal lesions. We found that PDVF sonography is useful for
      distinguishing abnormal masses from normal tissue, such as differentiating
      between isoechoic tumors and isoechoic glandular tissues, and discriminating
      entrapped fat lobules from isoechoic tumors. Furthermore, PDVF sonography was
      useful for determining whether intracystic echoes are attached to the cyst wall.
      CONCLUSIONS: Power Doppler VF imaging is a valuable adjunct tool to B-mode
      sonography in the evaluation of breast lesions.

PMID- 16798902
TI  - Cricoid cartilage on sonography in pediatric patients mimics a thyroid mass.
AB  - OBJECTIVE: The purpose of this study was to describe the sonographic appearance
      of the uncalcified cricoid cartilage in pediatric patients and illustrate how
      this can be easily confused with a thyroid mass or residual thyroid tissue after
      thyroidectomy. METHODS: We retrospectively reviewed the sonographic and computed
      tomographic examinations performed on 4 adolescent patients. Two patients had
      either thyroid cancer or thyroid nodules, and 2 healthy patients were reviewed to
      show normal anatomy. Results were compared with the clinical and surgical
      findings in each patient. RESULTS: Computed tomographic and sonographic
      examinations showed the normal anatomic relationships and imaging appearance of
      the cricoid cartilage. Findings from a follow-up sonographic examination on a
      patient with treated thyroid cancer were initially interpreted as residual
      thyroid tissue, but another examination revealed that this tissue was actually
      uncalcified cricoid cartilage. Another patient who had intraoperative sonography
      verified these findings. CONCLUSIONS: Uncalcified cricoid cartilage in a
      pediatric patient appears on sagittal sonography as a round or ovoid structure
      with variable echogenicity, located posteromedial to the thyroid gland. Awareness
      of this structure's sonographic appearance should prevent unnecessary biopsy or
      surgery.

PMID- 16798903
TI  - Utility of sonography for the diagnosis of adductor avulsion injury ("thigh
      splints").

PMID- 16798904
TI  - Transvaginal sonographic findings of endometrial metastases of mammary ductal
      carcinoma.

PMID- 16798905
TI  - Recurrence of adenoid cystic carcinoma in the breast after lumpectomy and
      adjuvant therapy.

PMID- 16798906
TI  - Sonographic findings of an intraductal mucinous carcinoma.

PMID- 16798907
TI  - Metastatic alveolar soft part sarcoma of the breast.

PMID- 16798908
TI  - Heart failure and severe pulmonary hypertension secondary to a giant renal
      arteriovenous malformation.

PMID- 16798909
TI  - Vascular steal of renal transplant: sonographic diagnosis.

PMID- 16798910
TI  - Not every assistant is a physician assistant.

PMID- 16798911
TI  - Thyroid gland rupture after blunt cervical trauma.

PMID- 16798912
TI  - Novel oligodeoxynucleotide agonists of TLR9 containing N3-Me-dC or N1-Me-dG
      modifications.
AB  - Synthetic oligodeoxynucleotides containing unmethylated CpG motifs activate Toll
      Like Receptor 9 (TLR9). Our previous studies have shown the role of hydrogen-bond
      donor and acceptor groups of cytosine and guanine in the CpG motif and identified
      synthetic immunostimulatory motifs. In the present study to elucidate the
      significance of N3-position of cytosine and N1-position of guanine in the CpG
      motif, we substituted C or G of a CpG dinucleotide with N3-Me-cytosine or N1-Me
      guanine, respectively, in immunomodulatory oligodeoxynucleotides (IMOs). IMOs
      containing N-Me-cytosine or N-Me-guanine in C- or G-position, respectively, of
      the CpG dinucleotide showed activation of HEK293 cells expressing TLR9, but not
      TLR3, 7 or 8. IMOs containing N-Me-cytosine or N-Me-guanine modification showed
      activity in mouse spleen cell cultures, in vivo in mice, and in human cell
      cultures. In addition, IMOs containing N-Me-substitutions reversed antigen
      induced Th2 immune responses towards a Th1-type in OVA-sensitized mouse spleen
      cell cultures. These studies suggest that TLR9 tolerates a methyl group at N1
      position of G and a methyl group at N3-position of C may interfere with TLR9
      activation to some extent. These are the first studies elucidating the role of N3
      position of cytosine and N1-position of guanine in a CpG motif for TLR9
      activation and immune stimulation.

PMID- 16798913
TI  - Recombination R-triplex: H-bonds contribution to stability as revealed with minor
      base substitutions for adenine.
AB  - Several cellular processes involve alignment of three nucleic acids strands, in
      which the third strand (DNA or RNA) is identical and in a parallel orientation to
      one of the DNA duplex strands. Earlier, using 2-aminopurine as a fluorescent
      reporter base, we demonstrated that a self-folding oligonucleotide forms a
      recombination-like structure consistent with the R-triplex. Here, we extended
      this approach, placing the reporter 2-aminopurine either in the 5'- or 3'-strand.
      We obtained direct evidence that the 3'-strand forms a stable duplex with the
      complementary central strand, while the 5'-strand participates in non-Watson
      Crick interactions. Substituting 2,6-diaminopurine or 7-deazaadenine for adenine,
      we tested and confirmed the proposed hydrogen bonding scheme of the A*(T.A) R
      type triplet. The adenine substitutions expected to provide additional H-bonds
      led to triplex structures with increased stability, whereas the substitutions
      consistent with a decrease in the number of H-bonds destabilized the triplex. The
      triplex formation enthalpies and free energies exhibited linear dependences on
      the number of H-bonds predicted from the A*(T.A) triplet scheme. The enthalpy of
      the 10 nt long intramolecular triplex of -100 kJ x mol(-1) demonstrates that the
      R-triplex is relatively unstable and thus an ideal candidate for a transient
      intermediate in homologous recombination, t-loop formation at the mammalian
      telomere ends, and short RNA invasion into a duplex. On the other hand, the
      impact of a single H-bond, 18 kJ x mol(-1), is high compared with the overall
      triplex formation enthalpy. The observed energy advantage of a 'correct' base in
      the third strand opposite the Watson-Crick base pair may be a powerful mechanism
      for securing selectivity of recognition between the single strand and the duplex.

PMID- 16798914
TI  - Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals
      the molecular basis of tRNA recognition and specificity.
AB  - Aminoacyl-tRNA synthetases (aaRSs) are a family of enzymes responsible for the
      covalent link of amino acids to their cognate tRNAs. The selectivity and species
      specificity in the recognitions of both amino acid and tRNA by aaRSs play a vital
      role in maintaining the fidelity of protein synthesis. We report here the first
      crystal structure of human tryptophanyl-tRNA synthetase (hTrpRS) in complex with
      tRNA(Trp) and Trp which, together with biochemical data, reveals the molecular
      basis of a novel tRNA binding and recognition mechanism. hTrpRS recognizes the
      tRNA acceptor arm from the major groove; however, the 3' end CCA of the tRNA
      makes a sharp turn to bind at the active site with a deformed conformation. The
      discriminator base A73 is specifically recognized by an alpha-helix of the unique
      N-terminal domain and the anticodon loop by an alpha-helix insertion of the C
      terminal domain. The N-terminal domain appears to be involved in Trp activation,
      but not essential for tRNA binding and acylation. Structural and sequence
      comparisons suggest that this novel tRNA binding and recognition mechanism is
      very likely shared by other archaeal and eukaryotic TrpRSs, but not by bacterial
      TrpRSs. Our findings provide insights into the molecular basis of tRNA
      specificity and species-specificity.

PMID- 16798915
TI  - Dosimetry of 3 CBCT devices for oral and maxillofacial radiology: CB Mercuray,
      NewTom 3G and i-CAT.
AB  - OBJECTIVES: Cone beam computed tomography (CBCT), which provides a lower dose,
      lower cost alternative to conventional CT, is being used with increasing
      frequency in the practice of oral and maxillofacial radiology. This study
      provides comparative measurements of effective dose for three commercially
      available, large (12'') field-of-view (FOV), CBCT units: CB Mercuray, NewTom 3G
      and i-CAT. METHODS: Thermoluminescent dosemeters (TLDs) were placed at 24 sites
      throughout the layers of the head and neck of a tissue-equivalent human skull
      RANDO phantom. Depending on availability, the 12'' FOV and smaller FOV scanning
      modes were used with similar phantom positioning geometry for each CBCT unit.
      Radiation weighted doses to individual organs were summed using 1990 (E(1990))
      and proposed 2005 (E(2005 draft)) ICRP tissue weighting factors to calculate two
      measures of whole-body effective dose. Dose as a multiple of a representative
      panoramic radiography dose was also calculated. RESULTS: For repeated runs
      dosimetry was generally reproducible within 2.5%. Calculated doses in microSv
      [corrected] (E(1990), E(2005 draft)) were NewTom3G (45, 59), i-CAT (135, 193) and
      CB Mercuray (477, 558). These are 4 to 42 times greater than comparable panoramic
      examination doses (6.3 microSv [corrected] 13.3 mSv). Reductions in dose were
      seen with reduction in field size and mA and kV technique factors. CONCLUSIONS:
      CBCT dose varies substantially depending on the device, FOV and selected
      technique factors. Effective dose detriment is several to many times higher than
      conventional panoramic imaging and an order of magnitude or more less than
      reported doses for conventional CT.

PMID- 16798916
TI  - Evaluation of surface and volume rendering in 3D-CT of facial fractures.
AB  - OBJECTIVES: Three-dimensional computed tomography (3D-CT) of facial fractures has
      been reported as beneficial using surface (SR) and volume rendering (VR). There
      are controversial statements concerning the preferable algorithm. The purpose of
      this study was to evaluate and compare SR and VR for clinical 3D-CT in facial
      fractures on an experimental basis. METHODS: Multislice CT was obtained in 22
      patients with facial fractures using two data acquisition protocols. Five SR and
      VR post-processing protocols were applied. Five assessors independently evaluated
      the quality of visualization of the fracture gap and dislocated fragments as well
      as the overall image quality using a five-point rating scale. The potential
      benefit of the 3D-images for radiological diagnosis and presentation was
      evaluated. The influence of the data acquisition protocol was analysed. RESULTS:
      SR in general achieved better evaluation scores than VR at corresponding
      thresholds. Variation of evaluation scores for all criteria was found for SR and
      VR depending on the segmentation threshold. Apart from the overall image quality
      no significant influence of the data acquisition technique was found for the
      evaluated criteria. CONCLUSIONS: SR provided sufficient and time efficient means
      for 3D-visualization of facial fractures in this study. No diagnostic benefit of
      VR over SR was found.

PMID- 16798917
TI  - Diagnostic criteria for the detection of mandibular osteomyelitis using cone-beam
      computed tomography.
AB  - OBJECTIVES: To investigate the usefulness of cone-beam computed tomography (CBCT)
      in cases of suspected osteomyelitis (OM) of the mandible. METHODS: 13 patients
      with clinical suspected OM of the mandible underwent cone-beam computed
      tomography with the NewTom QR-DVT 9000. After CBCT revealed signs confirming the
      diagnosis of OM, biopsies were performed. Only cases in which histology confirmed
      the OM were included in this study. RESULTS: CBCT sufficiently depicts OM-typical
      lesions like osteolytic and osteosclerotic areas as well as periosteal reaction,
      ill-defined cortical borders and sequestra. CONCLUSIONS: Because the local
      extension of the disease and its relationship to anatomic structures can be
      sufficiently detected by CBCT, we see an important additional indication for the
      usage of CBCT. With regard to distinct cases CBCT combined with scintigraphy
      seems to be a sufficient diagnostic strategy concerning suspected OM.

PMID- 16798918
TI  - Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the
      jaws.
AB  - OBJECTIVES: It is important to recognize osteonecrosis of the jaws in patients
      treated with bisphosphonates because an early diagnosis can make a significant
      difference to the outcome of the disease. The aim of this study is to describe
      the radiological features of bisphosphonate osteonecrosis (BON) in order to aid
      its prompt recognition. METHODS: A conventional radiograph, a computed tomograph
      (CT), a magnetic resonance image (MRI) and a 99Tc(m)-MDP 3-phase bone scan were
      carried out for 11 patients with BON. The main imaging findings of osteonecrosis
      are described. RESULTS: Conventional radiography and CT displayed osteolytic
      lesions with the involvement of cortical bone. MRI demonstrated the
      characteristic features of osteonecrosis and the oedema of soft tissues. Both CT
      and MRI were very useful in defining the extent of the lesions. 99Tc(m)-MDP three
      phase bone scan was the most sensitive tool to detect the osteonecrosis at an
      early stage. CONCLUSIONS: 99Tc(m)-MDP three-phase bone scans who could be used as
      a screening test to detect subclinical osteonecrosis in patients who have
      received bisphosphonates. CT scans and MRI are useful in defining the features
      and extent of osteolytic lesions.

PMID- 16798919
TI  - Accuracy and precision of a densitometric tool for jaw bone.
AB  - OBJECTIVES: To develop a digital densitometric tool for jaw bone to analyse
      intraoral radiographs. To assess precision and accuracy for this tool and
      determine the minimal detection threshold for density changes. METHODS: Bone
      samples deriving from the premolar region of 47 human mandibles were selected for
      analysis. The samples were obtained from adult cadavers in the department of
      anatomy (Faculty of Medicine, KULeuven) with ethical approval. Digital
      radiography was performed on all bone samples. Direct volumetric measurements
      served as gold standard density values and allowed determination of accuracy.
      Dual-energy X-ray absorptiometry (DXA) scans were performed on all specimens. For
      all radiographs, density in mm Al eq was calculated using custom-made software,
      Osteop. Precision and intraobserver and interobserver reliability of this method
      were assessed. The bone specimens were progressively decalcified. At standard
      time intervals the percentage of decalcification was calculated. At each
      decalcification step, radiographs were taken and analysed. RESULTS: CV was always
      lower than 3%, which points to a good precision of the method. Correlation
      between the density measurements in mm Al eq and the DXA results was 0.9, for the
      density measurements in mm Al eq and the direct density measurements r was 0.5.
      The custom-made software was able to detect a change in bone mineralization of
      6.6%. CONCLUSIONS: The present method for bone densitometric analysis offers
      potentials for clinical evaluation of bone density and minute bone density
      changes in the jaw bone.

PMID- 16798920
TI  - Diagnostic performance of general dental practitioners after lecture in
      identifying post-menopausal women with low bone mineral density by panoramic
      radiographs.
AB  - OBJECTIVES: Mandibular cortical erosion detected on panoramic radiographs may be
      useful for identifying post-menopausal women with low skeletal bone mineral
      density (BMD). The purposes of this study were to calculate the diagnostic
      performance of general dental practitioners (GDPs) who attended a lecture on
      identifying post-menopausal women with low BMD from findings on panoramic
      radiographs and to evaluate the influence of GDPs' age on diagnostic performance.
      METHODS: After a 1 h lecture, 111 GDPs were asked to classify the mandibular
      cortex (normal or eroded) on panoramic radiographs obtained from 100 post
      menopausal women who have had skeletal BMD assessment. Low BMD was defined as a
      BMD T score of -1.0 or less. Diagnostic performance was analysed by comparing two
      groups classified by mandibular cortex (women with normal cortex and women with
      any eroded cortex) with those classified by BMD (women with normal BMD and women
      with low BMD). RESULTS: The mean sensitivity, specificity, positive predictive
      value, negative predictive value, accuracy and likelihood ratio for a positive
      risk result were 73.0% (95% confidence interval [CI]; 71.3 to 74.7%), 49.0% (95%
      CI; 46.4 to 51.5%), 66.9% (95% CI; 66.0 to 67.8%), 57.0% (95% CI; 55.8 to 58.2%),
      62.9% (95% CI; 62.1 to 63.7%) and 1.51 (95% CI; 1.44 to 1.58), respectively.
      GDPs' age did not influence diagnostic performance. CONCLUSIONS: Our results
      suggest that 73.0% of women who had low skeletal BMD can be identified by GDPs
      after a lecture on the use of panoramic radiographs as an aid in diagnosing low
      BMD; however, the diagnostic performance may not be influenced by GDPs' age.

PMID- 16798921
TI  - Digital camera resolution and proximal caries detection.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of proximal caries detection from
      digitized film images captured by a digital camera at different resolution
      settings. METHODS: Twenty-five periapical radiographs of 50 premolar and 25 molar
      teeth were photographed using a digital camera, Sony Cyber-shot, DSC-S75 at three
      different resolution settings: 640 x 480, 1280 x 960 and 1600 x 1200. Seventy
      five digital images were transferred to a computer, saved and opened using ACDSee
      software. In addition, a PowerPoint slide was made from each digital image. Five
      observers scored three groups of images (the films, the displayed 1:1 digital
      images on the ACDSee software, and the PowerPoint slides) for the existence of
      proximal caries using a 5-point confidence scale, and the depth of caries on a 4
      point scale. Ground sections of the teeth were used as the gold standard. Az
      values under the receiver operating characteristic (ROC) curve of each group of
      images and at different resolutions were compared using the Friedman and Wilcoxon
      signed rank tests. Mean different values between the lesions' depth interpreted
      by the observers and that of the gold standard were analysed. RESULTS: Films
      showed the highest Az values. Only the 1280 x 960 images on the ACDSee software
      showed no significant difference of the Az value from the films (P=0.28). The
      digital images from three resolution settings on the PowerPoint slides showed no
      significant differences, either among each other or between them and the films.
      For caries depth, the 1280 x 960 images showed lower values of mean difference in
      enamel lesions compared with the other two resolution groups. CONCLUSIONS: This
      study showed that in order to digitize conventional films, it was not necessary
      to use the highest camera resolution setting to achieve high diagnostic accuracy
      for proximal caries detection. The 1280 x 960 resolution setting of the digital
      camera demonstrated comparable diagnostic accuracy with film and was adequate for
      digitizing radiographs for caries detection.

PMID- 16798922
TI  - Comparison of peri-implant bone level assessment in digitized conventional
      radiographs and digital subtraction images.
AB  - OBJECTIVES: Radiographic assessment of marginal bone height is included in
      longitudinal control of osseointegrated implants. However, accurate and
      reproducible results are difficult to obtain. The aim of the present study was to
      examine the differences between linear measurements in digitized radiographs (DR)
      and digital subtraction images (DSI) around endosseous implants and the
      interobserver variability. METHODS: The bone height around 30 implants in 22
      patients was assessed by 5 observers. Standardized periapical radiographs were
      obtained just after the surgery and 4 months later. The radiographs were
      digitized and manipulated by means of EMAGO software, and linear and logarithmic
      DSIs were produced. Furthermore, the logarithmic subtraction was enhanced with
      the use of a filter. The observers had the DRs and three methods of subtraction
      to assess bone height. ANOVA statistical procedures were applied to analyse
      differences between the observers in the four assessed images and the Tukey test
      was used to evaluate the differences between the images. RESULTS: Comparison of
      the bone height assessments indicated significantly (P<0.05) higher values in the
      DR than the three methods of DSI. The observers also had a statistically
      significant variability in this assessment (P=0.00003). CONCLUSIONS: DSI
      demonstrated lower values of linear measurements of the bone height around
      endosseous implants, compared with DR. Interobserver variability should be
      considered when comparing values from follow-up studies.

PMID- 16798923
TI  - Accuracy of direct digital radiography in the study of the root canal type.
AB  - OBJECTIVES: To determine the accuracy of direct digital radiography (DDR) in the
      study of the root canal type. A sub aim was to assess intraexaminer and
      interexaminer agreement for this feature using DDR system. METHODS: 100 recently
      extracted permanent maxillary first premolars from Chinese population were used.
      Standardized periapical DDR images were taken from a buccolingual and mesiodistal
      direction. Then the specimens were accessed, injected with dye, demineralized,
      dehydrated and finally were cleared. The DDR images were evaluated based on the
      root canal type by two independent trained post-graduate students (examiner A and
      B) twice at an interval of 2 weeks. The cleared teeth were examined under 5 x
      magnification using a dental operating microscope by another experienced
      endodontist, and the data of root canal type were collected. RESULTS: The Kappa
      values for the agreement between the examiner A and the clearing technique were
      0.3793 and 0.329, between the examiner B and the clearing technique were 0.2481
      and 0.2184. While the Kappa values between the two observations of each examiner
      were 0.7704 and 0.7725, between the two examiners they were 0.537 and 0.4793,
      respectively. CONCLUSIONS: The intraexaminer agreement was good, and the
      interexaminer agreement was moderate, but the agreement between either DDR
      examiner and the clearing technique was poor, indicating the limited value of DDR
      alone when studying root canal type.

PMID- 16798924
TI  - Digital panoramic radiography: a reliable method to diagnose carotid artery
      atheromas?
AB  - OBJECTIVES: The aim of the present study is to evaluate the panoramic radiographs
      of 4106 patients for carotid artery atheromas (CAAs) and to correlate our
      findings with the literature. MATERIALS AND METHODS: The digital panoramic
      radiographs of 4106 dental patients (2428 female, 1678 male) were evaluated.
      Radiographs of patients 40 years of age or older were randomly chosen from a
      computer database. CAA findings were defined as radiopaque masses adjacent to the
      cervical vertebrae at or below the intervertebral space between C3 and C4 on the
      panoramic radiograph. The patients who had CAA findings were contacted by
      telephone, and some of them agreed to further evaluation. Evaluation included
      carotid ultrasound, ECG, echocardiography and treadmill exercise testing at the
      Department of Cardiology. RESULTS: Of 4106 patients, 88 patients (2.1%; 70
      female, 18 male) had one or more radiopaque mass detected on digital images. All
      88 patients with CAA findings were contacted by telephone and 23 agreed to
      further evaluation at the university hospital. Of these 23 patients, 8 (34.7%)
      had CAAs on carotid ultrasound and 15 (65.3%) had normal carotid arteries. From
      these eight patients with CAAs on Doppler ultrasound, 7 (30.4%) had plaques that
      were not haemodynamically significant and only one (4.3%) had significant plaque.
      The patient with severe carotid artery stenosis consequently underwent
      endarterectomy operation. There were no statistically significant differences
      between male and female in CAAs (P>0.05). CONCLUSION: Digital panoramic images
      may have some diagnostic value for detecting CAAs and this early diagnosis could
      potentially increase the length and quality of life for people with CAAs.

PMID- 16798925
TI  - The effect of dose reduction on the detection of anatomical structures on
      panoramic radiographs.
AB  - OBJECTIVES: The aim was to evaluate the effect of dose reduction on diagnostic
      accuracy using different screen-film combinations and digital techniques for
      panoramic radiography. METHODS: Five observers assessed 201 pairs of panoramic
      radiographs (a total of 402 panoramic radiographs) taken with the Orthophos Plus
      (Sirona, Bensheim, Germany), for visualization of 11 anatomical structures on
      each side, using a 3-point scale -1, 0 and 1. Two radiographs of each patient
      were taken at two different times (conventional setting and setting with
      decreased dose, done by increasing tube potential settings or halving tube
      current). To compare the dose at different tube potential settings dose-length
      product was measured at the secondary collimator. Films with medium and regular
      intensifying screens (high and low tube potential settings) and storage phosphor
      plates (low tube potential setting, tube current setting equivalent to regular
      intensifying screen and halved) were compared. The five observers made 27 610
      assessments. Intrarater agreement was expressed by Cohen's kappa coefficient.
      RESULTS: The results demonstrated an equivalence of regular screens (low tube
      potential setting) and medium screens (high and low tube potential settings). A
      significant difference existed between medium screens (low tube potential
      setting, mean score 0.92) and the group of regular film-screen combinations at
      high tube potential settings (mean score 0.89) and between all film-screen
      combinations and the digital system irrespective of exposure (mean score below
      0.82). There were no significant differences between medium and regular screens
      (mean score 0.88 to 0.92) for assessment of the periodontal ligament space, but
      there was a significant difference compared with the digital system (mean score
      below 0.76). The kappa coefficient for intrarater agreement was moderate (0.55).
      CONCLUSIONS: New regular intensifying screens can replace medium screens at low
      tube potential settings. Digital panoramic radiographs should be taken at low
      tube potential levels with an exposure equivalent at least to a regular
      intensifying screen.

PMID- 16798926
TI  - Scatter radiation in cephalometric radiography: the effects of grid and
      collimation.
AB  - OBJECTIVES: To measure the scatter fraction in cephalometric radiography with and
      without a grid and to estimate the patient's dose reduction by using a specially
      fabricated collimator without a grid. METHODS: A 16 cm thick water-equivalent
      phantom was used to measure the scatter fraction. The projection geometry was the
      same as our conventional one, i.e. the distance from the X-ray source to the
      centre of the phantom was 200 cm. A photostimulable phosphor plate was used as an
      X-ray sensor and was 20 cm from the centre of the phantom. The measurements were
      performed in four combinations: with an antiscatter grid in place, with a
      specially fabricated collimator in place, with neither in place, and with both in
      place. The images of a human dried skull were obtained by using the above
      parameters and were subjectively assessed for a visibility of several reference
      points. RESULT: The scatter fraction in the regularly collimated geometry with
      the antiscatter grid in place was 0.35 for a relative exposure of 1. With the
      antiscatter grid removed, the scatter fraction increased to 0.68, but the
      relative exposure was reduced to 0.3. With a special collimator, the scatter
      fraction was reduced to some extent in all instances, but the exposure was
      reduced to 0.45. The visibility of the reference points was acceptable in all
      conditions. CONCLUSION: In cephalometric radiography, removal of the antiscatter
      grid yields a significant reduction in exposure with no significant loss of
      information.

PMID- 16798927
TI  - Radiographic features of the jaws and teeth in thalassaemia major.
AB  - OBJECTIVES: This investigation aimed to compare the radiographic changes and root
      and crown-body lengths of the mandibular first permanent molar in a group of
      thalassaemic patients with a control group, matched for age and sex. METHODS:
      Panoramic radiographs of 50 thalassaemic patients and 50 controls were examined
      for the presence of radiological changes. Crown body and root lengths were
      determined using the method of Seow and Lai. The average lengths were calculated
      and compared between the two groups. RESULTS: The mean crown-body and root
      lengths of the mandibular first molar of patients with thalassaemia major were
      9.58+/-0.83 mm and 11.89+/-1.33 mm, while those for the control group were
      10.45+/-0.78 mm and 12.78+/-1.67 mm, respectively. A significant difference
      (P<0.05) was found between the mean crown-body and root values of the two groups.
      A significant difference (P<0.05) was also found between thalassaemic patients
      and controls in the occurrence of spiky-shaped roots, root and crown lengths,
      taurodontism, attenuated lamina dura, enlarged bone marrow spaces, small
      maxillary sinuses, faint inferior alveolar canal and thin cortex of the mandible.
      CONCLUSIONS: While thalassaemia major may not be associated with the occurrence
      of either vascular canals or prominent antegonial notch, spiky-shaped and short
      roots, taurodonts, attenuated lamina dura, enlarged bone marrow spaces, small
      maxillary sinuses, absence of inferior alveolar canal and thin cortex of the
      mandible were found to be reliable diagnostic criteria for thalassaemia major.

PMID- 16798928
TI  - Changes in condylar mobility and radiographic alterations after treatment in
      patients with non-reducing disc displacement of the temporomandibular joint.
AB  - OBJECTIVES: The purpose of this study was to examine changes in condylar mobility
      and morphological changes in the affected condyles after treatment in patients
      with non-reducing disc displacement of the temporomandibular joint (TMJ).
      METHODS: Changes in condylar mobility and morphological changes of the condyle
      were examined radiographically in 55 patients who were diagnosed as having non
      reducing disc displacement of the unilateral TMJ and had received pumping with
      injection of sodium hyaluronate. In all patients, standardized lateral oblique
      transcranial radiographs and panoramic jaw tomograms were taken both at initial
      visit and at 12 months or more follow-up (mean 28.1 months after treatment; range
      12-104 months). 42 joints in 21 persons with no current or previous TMJ symptoms
      served as a control. RESULTS: Clinical signs and symptoms improved after
      treatment in the patients. Condylar mobility significantly increased after
      treatment in patients (P<0.001), although it did not reach levels of the control
      group. Frequency of radiographic changes of the condyle significantly increased
      after treatment (P<0.005). In most of the patients, no or only mild changes were
      observed. Frequency of changes of the condyle in patients at follow-up was
      significantly greater than that in controls (P<0.001). CONCLUSIONS: In the
      patients, condylar mobility increased in the subsequent course after treatment.
      However, bony changes of the condyle appeared more frequently. Long term-follow
      up after treatment on bony changes of the condyle seems to be necessary in
      patients with non-reducing disc displacement of the TMJ.

PMID- 16798930
TI  - Soft tissue lipoma with the radiographic appearance of a neoplasm within the
      mandibular canal.
AB  - Lipomas and lipoma variants are common soft tissue tumours but are not commonly
      found in the oral and maxillofacial region. We report a case of a classic lipoma
      located on the medial aspect of the mandibular ramus, but not within bone, first
      seen by an oral and maxillofacial surgeon during treatment planning for routine
      extractions. Initial panoramic radiography indicated an expansive tumour in the
      area of the mandibular foramen and proximal end of the mandibular canal,
      apparently within the body of the mandible. Subsequent imaging with CT revealed a
      well-circumscribed soft tissue tumour on the medial aspect of the left mandibular
      ramus, not within the bone itself. Histological analysis of the operative
      specimen indicated a classic lipoma.

PMID- 16798929
TI  - Dose reduction of intraoral dental radiography in Spain.
AB  - OBJECTIVES: To assess the influence of new European Union (EU) legislation on
      radiation doses in intraoral dental radiography in Spain. METHODS: A total of 10
      109 official reports from Spanish dental offices covering the period 1996-2003
      were analysed. RESULTS: The results point to a dose reduction of 19% in 7 years,
      with a mean dose of 3.11 mGy being administered in 2003. The third quartile value
      in 2002 was 4.8 mGy. Taking the EU recommended dose of 4 mGy as standard, 73.3%
      (2002) and 77.3% (2003) of installations are in compliance with the EU
      recommendations in Spain. However, there has been no further reduction in the
      last 3 years. The results showed that Ultraspeed dental X-ray film was used by
      77.6% of the dentists in 1996-1997 and 82.3 in 2003. There was infrequent use of
      E-speed films (0.6%) and F-speed films (9.6%) in 2003. Statistical analysis
      pointed to significant differences between the doses administered and the type of
      processing used, the lowest exposures being measured in digital systems, which
      used significantly lower doses than both manual and automatic development, and
      when conventional radiographic films were used. CONCLUSION: The introduction of
      new legislation has resulted in a gradual reduction in the dose administered in
      intraoral dental radiology in Spain.

PMID- 16798931
TI  - Inflammatory reaction to foreign body (amalgam) in the maxillary sinus
      misdiagnosed as an ethmoid tumor.
AB  - A patient with chronic unilateral maxillary sinusitis caused by a foreign body
      (dental amalgam) and mistaken diagnosis of extensive ethmoid neoplasm is
      presented. The imitation of tumour symptoms was due to a long presence of foreign
      body in the maxillary sinus and chronic inflammation of maxillary, ethmoid and
      sphenoid sinuses.

PMID- 16798932
TI  - Fine-needle aspiration cytology of metaplastic carcinoma of the breast.
AB  - BACKGROUND: Metaplastic carcinoma of the breast encompasses a heterogeneous group
      of tumours with variable components of sarcomatoid, squamous or poorly
      differentiated carcinomas. AIM: To review a series of 19 cytological preparations
      of metaplastic carcinomas to assess diagnostic cytological features. METHODS: 17
      cases of fine-needle aspirates of histologically proven metaplastic carcinomas (4
      monophasic spindle cell carcinomas, 4 squamous cell carcinomas and 11 biphasic
      tumours) were reviewed, with an emphasis on the presence of poorly differentiated
      carcinoma, squamous cell carcinoma, atypical spindle cells, benign stromal
      fragments and necrosis. RESULTS: All cases were diagnosed as malignant, with 68%
      of cases showing moderate to high cellularity, and 47% showing necrosis. If the
      tumours were analysed according to the constituting components histologically, 7,
      15 and 8 cases, respectively, possess poorly differentiated carcinoma cells,
      sarcomatoid malignant cells and squamous carcinoma cells, whereas these
      components were cytologically identified in 11, 10 and 7 cases, respectively.
      Dual tumour populations were identified in only 5 of the 11 biphasic carcinomas
      in the cytological preparations; and the stromal material was cytologically
      identified in the only case with chondroid stroma. CONCLUSIONS: Identification of
      metaplastic carcinoma in cytology remains problematic. There seems to be
      morphological overlap between various components. The identification of dual
      components, unequivocal squamous carcinoma cells and chondroid stroma is helpful
      for diagnosis, but it is uncommon. The presence of poorly differentiated
      carcinoma cells with a suggestion of focal spindle morphology is another clue to
      the suggestion of metaplastic carcinoma.

PMID- 16798934
TI  - Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the
      oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma.
AB  - BACKGROUND: The down regulation of protein p27(kip1) (p27) in most cases of
      thyroid cancer has relevant diagnostic and prognostic implications. However, the
      oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma expresses more
      p27 than benign oxyphilic lesions do. AIM: To evaluate the mechanism underlying
      this difference in expression of p27. METHODS: Because high levels of cyclin D3
      lead to p27 accumulation in cell lines and clinical samples of thyroid cancer,
      the immunocytochemical pattern of cyclin D3 in oxyphilic (n = 47) and non
      oxyphilic (n = 70) thyroid neoplasms was investigated. RESULTS: In the whole
      study sample, there was a significant correlation between p27 and cyclin D3
      expression (Spearman's r: 0.64; p<0.001). The expression of cyclin D3 and p27 was
      significantly higher in the oxyphilic variant of follicular carcinomas than in
      non-oxyphilic carcinomas (p<0.001). In the former, cyclin D3 overexpression and
      p27 accumulation were observed in a median of 75% and 55% of cells, respectively.
      In co-immunoprecipitation experiments, the level of p27-bound cyclin D3 was much
      higher in oxyphilic neoplasias than in normal thyroids and other thyroid tumours.
      CONCLUSION: These results show that increased p27 expression in the oxyphilic
      (Hurthle cell) variant of follicular thyroid carcinoma results from cyclin D3
      overexpression.

PMID- 16798933
TI  - Our approach to follicular-patterned lesions of the thyroid.
AB  - Follicular-patterned lesions of the thyroid are common; these include
      hyperplastic/adenomatoid nodules, follicular adenoma, follicular carcinoma and
      follicular variants of papillary carcinoma. Most of these lesions can be
      diagnosed with ease; however, there is a controversial subgroup. In this review,
      we present our diagnostic approach based on our experience with the histological
      diagnosis of these tumours, which can help in appropriate clinical management.

PMID- 16798935
TI  - Xanthomatosis of the gastrointestinal tract with focus on small bowel
      involvement.

PMID- 16798936
TI  - Phorbol 12-myristate 13-acetate protects against tumor necrosis factor (TNF)
      induced necrotic cell death by modulating the recruitment of TNF receptor 1
      associated death domain and receptor-interacting protein into the TNF receptor 1
      signaling complex: Implication for the regulatory role of protein kinase C.
AB  - Protein kinase C (PKC) triggers cellular signals that regulate proliferation or
      death in a cell- and stimulus-specific manner. Although previous studies have
      demonstrated that activation of PKC with phorbol 12-myristate 13-acetate (PMA)
      protects cells from apoptosis induced by a number of mechanisms, including death
      receptor ligation, little is known about the effect or mechanism of PMA in the
      necrotic cell death. Here, we demonstrate that PMA-mediated activation of PKC
      protects against tumor necrosis factor (TNF)-induced necrosis by disrupting
      formation of the TNF receptor (TNFR)1 signaling complex. Pretreatment with PMA
      protected L929 cells from TNF-induced necrotic cell death in a PKC-dependent
      manner, but it did not protect against DNA-damaging agents, including doxorubicin
      (Adriamycin) and camptothecin. Analysis of the upstream signaling events affected
      by PMA revealed that it markedly inhibited the TNF-induced recruitment of TNFR1
      associated death domain protein (TRADD) and receptor-interacting protein (RIP) to
      TNFR1, subsequently inhibiting TNF-induced activation of nuclear factor-kappaB
      and c-Jun NH2-terminal kinase (JNK). However, JNK inhibitors do not significantly
      affect TNF-induced necrosis, suggesting that the inhibition of JNK activation by
      PMA is not part of the antinecrotic mechanism. In addition, PMA acted as an
      antagonist of TNF-induced reactive oxygen species (ROS) production, thereby
      suppressing activation of ROS-mediated poly(ADP-ribose)polymerase (PARP), and
      thus inhibiting necrotic cell death. Furthermore, during TNF-induced necrosis,
      PARP was significantly activated in wild-type mouse embryonic fibroblast (MEF)
      cells but not in RIP-/- or TNFR-associated factor 2-/-MEF cells. Taken together,
      these results suggest that PKC activation ensures effective shutdown of the death
      receptor-mediated necrotic cell death pathway by modulating formation of the
      death receptor signaling complex.

PMID- 16798937
TI  - Ghrelin receptor inverse agonists: identification of an active peptide core and
      its interaction epitopes on the receptor.
AB  - [D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P functions as a low-potency antagonist
      but a high-potency full inverse agonist on the ghrelin receptor. Through a
      systematic deletion and substitution analysis of this peptide, the C-terminal
      carboxyamidated pentapeptide wFwLX was identified as the core structure, which
      itself displayed relatively low inverse agonist potency. Mutational analysis at
      17 selected positions in the main ligand-binding crevice of the ghrelin receptor
      demonstrated that ghrelin apparently interacts only with residues in the middle
      part of the pocket [i.e., between transmembrane (TM)-III, TM-VI and TM-VII]. In
      contrast, the inverse agonist peptides bind in a pocket that extends all the way
      from the extracellular end of TM-II (AspII:20) across between TM-III and TM
      VI/VII to TM-V and TM-IV. The potency of the main inverse agonist could be
      improved up to 20-fold by a number of space-generating mutants located relatively
      deep in the binding pocket at key positions in TM-III, TM-IV and TM-V. It is
      proposed that the inverse agonists prevent the spontaneous receptor activation by
      inserting relatively deeply across the main ligand-binding pocket and sterically
      blocking the movement of TM-VI and TM-VII into their inward-bend, active
      conformation. The combined structure-functional analysis of both the ligand and
      the receptor allowed for the design of a novel, N-terminally Lys-extended analog
      of wFwLL, which rescued the high-potency, selective inverse agonism that was
      dependent upon both AspII:20 and GluIII:09. The identified pharmacophore can
      possibly serve as the basis for targeted discovery of also nonpeptide inverse
      agonists for the ghrelin receptor.

PMID- 16798938
TI  - Bisindenoisoquinoline bis-1,3-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2
      c]isoquinoline)-6-propylamino}propane bis(trifluoroacetate) (NSC 727357), a DNA
      intercalator and topoisomerase inhibitor with antitumor activity.
AB  - Indenoisoquinolines are topoisomerase (Top) I inhibitors developed to overcome
      some of the limitations of camptothecins and expand their anticancer spectrum.
      Bis-1,3-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino}
      propane bis(trifluoroacetate) (NSC 727357) is a novel dimeric indenoisoquinoline
      derivative with potent antiproliferative activity in the NCI-60 cell line panel,
      promising hollow fiber activity (score of 32) and activity against xenografts.
      Submicromolar concentrations of the bisindenoisoquinoline NSC 727357 induce Top1
      cleavage complexes at specific sites in biochemical assays. At higher
      concentrations, inhibition of Top1 catalytic activity and DNA intercalation is
      observed. NSC 727357 also induces a limited number of Top2-DNA cleavage
      complexes. In contrast to the effect of other Top1 inhibitors, cells treated with
      the bisindenoisoquinoline NSC 727357 show an arrest of cell cycle progression in
      G(1) with no significant inhibition of DNA synthesis after a short exposure to
      the drug. Moreover, unlike camptothecin and the indenoisoquinoline MJ-III-65 (NSC
      706744, 6-[3-(2-hydroxyethyl)aminopropyl]-5,6-dihydro-5,11-diketo-2,3-dimethoxy
      (methylenedioxy)-11H-indeno[1,2-c]isoquinoline hydrochloride), the cytotoxicity
      of bisindenoisoquinoline NSC 727357 is only partially dependent on Top1 and p53,
      indicating that this drug has additional targets besides Top1 and Top2.

PMID- 16798939
TI  - RCN1-regulated phosphatase activity and EIN2 modulate hypocotyl gravitropism by a
      mechanism that does not require ethylene signaling.
AB  - The roots curl in naphthylphthalamic acid1 (rcn1) mutant of Arabidopsis
      (Arabidopsis thaliana) has altered auxin transport, gravitropism, and ethylene
      response, providing an opportunity to analyze the interplay between ethylene and
      auxin in control of seedling growth. Roots of rcn1 seedlings were previously
      shown to have altered auxin transport, growth, and gravitropism, while rcn1
      hypocotyl elongation exhibited enhanced ethylene response. We have characterized
      auxin transport and gravitropism phenotypes of rcn1 hypocotyls and have explored
      the roles of auxin and ethylene in controlling these phenotypes. As in roots,
      auxin transport is increased in etiolated rcn1 hypocotyls. Hypocotyl gravity
      response is accelerated, although overall elongation is reduced, in etiolated
      rcn1 hypocotyls. Etiolated, but not light grown, rcn1 seedlings also overproduce
      ethylene, and mutations conferring ethylene insensitivity restore normal
      hypocotyl elongation to rcn1. Auxin transport is unaffected by treatment with the
      ethylene precursor 1-aminocyclopropane carboxylic acid in etiolated hypocotyls of
      wild-type and rcn1 seedlings. Surprisingly, the ethylene insensitive2-1 (ein2-1)
      and ein2-5 mutations dramatically reduce gravitropic bending in hypocotyls.
      However, the ethylene resistant1-3 (etr1-3) mutation does not significantly
      affect hypocotyl gravity response. Furthermore, neither the etr1 nor the ein2
      mutation abrogates the accelerated gravitropism observed in rcn1 hypocotyls,
      indicating that both wild-type gravity response and enhanced gravity response in
      rcn1 do not require an intact ethylene-signaling pathway. We therefore conclude
      that the RCN1 protein affects overall hypocotyl elongation via negative
      regulation of ethylene synthesis in etiolated seedlings, and that RCN1 and EIN2
      modulate hypocotyl gravitropism and ethylene responses through independent
      pathways.

PMID- 16798940
TI  - Synergism between RPBF Dof and RISBZ1 bZIP activators in the regulation of rice
      seed expression genes.
AB  - The Dof (DNA binding with one finger) transcriptional activator rice (Oryza
      sativa) prolamin box binding factor (RPBF), which is involved in gene regulation
      of rice seed storage proteins, has been isolated from rice cDNA expressed
      sequence tag clones containing the conserved Dof. RPBF is found as a single gene
      per haploid genome. Comparison of RPBF genomic and cDNA sequences revealed that
      the genomic copy is interrupted by one long intron of 1,892 bp in the 5'
      noncoding region. We demonstrated by transient expression in rice callus
      protoplasts that the isolated RPBF trans-activated several storage protein genes
      via an AAAG target sequence located within their promoters, and with methylation
      interference experiments the additional AAAG-like sequences in promoters of genes
      expressed in maturing seeds were recognized by the RPBF protein. Binding was
      sequence specific, since mutation of the AAAG motif or its derivatives decreased
      both binding and trans-activation by RPBF. Synergism between RPBF and RISBZ1
      recognizing the GCN4 motif [TGA(G/C)TCA] was observed in the expression of many
      storage protein genes. Overexpression of both transcription factors gave rise to
      much higher levels of expression than the sum of individual activities elicited
      by either RPBF or RISBZ1 alone. Furthermore, mutation of recognition sites
      suppressed reciprocal trans-activation ability, indicating that there are mutual
      interactions between RISBZ1 and RPBF. The RPBF gene is predominantly expressed in
      maturing endosperm and coordinately expressed with seed storage protein genes,
      and is involved in the quantitative regulation of genes expressed in the
      endosperm in cooperation with RISBZ1.

PMID- 16798941
TI  - Natural variation for carbohydrate content in Arabidopsis. Interaction with
      complex traits dissected by quantitative genetics.
AB  - Besides being a metabolic fuel, carbohydrates play important roles in plant
      growth and development, in stress responses, and as signal molecules. We
      exploited natural variation in Arabidopsis (Arabidopsis thaliana) to decipher the
      genetic architecture determining carbohydrate content. A quantitative trait locus
      (QTL) approach in the Bay-0 x Shahdara progeny grown in two contrasting nitrogen
      environments led to the identification of 39 QTLs for starch, glucose, fructose,
      and sucrose contents representing at least 14 distinct polymorphic loci. A major
      QTL for fructose content (FR3.4) and a QTL for starch content (ST3.4) were
      confirmed in heterogeneous inbred families. Several genes associated with carbon
      (C) metabolism colocalize with the identified QTL. QTLs for senescence-related
      traits, and for flowering time, water status, and nitrogen-related traits,
      previously detected with the same genetic material, colocalize with C-related
      QTLs. These colocalizations reflect the complex interactions of C metabolism with
      other physiological processes. QTL fine-mapping and cloning could thus lead soon
      to the identification of genes potentially involved in the control of different
      connected physiological processes.

PMID- 16798942
TI  - Extracellular Ca2+ ameliorates NaCl-induced K+ loss from Arabidopsis root and
      leaf cells by controlling plasma membrane K+ -permeable channels.
AB  - Calcium can ameliorate Na+ toxicity in plants by decreasing Na+ influx through
      nonselective cation channels. Here, we show that elevated external [Ca2+] also
      inhibits Na+ -induced K+ efflux through outwardly directed, K+ -permeable
      channels. Noninvasive ion flux measuring and patch-clamp techniques were used to
      characterize K+ fluxes from Arabidopsis (Arabidopsis thaliana) root mature
      epidermis and leaf mesophyll under various Ca2+ to Na+ ratios. NaCl-induced K+
      efflux was not related to the osmotic component of the salt stress, was inhibited
      by the K+ channel blocker TEA+, was not mediated by inwardly directed K+ channels
      (tested in the akt1 mutant), and resulted in a significant decrease in cytosolic
      K+ content. NaCl-induced K+ efflux was partially inhibited by 1 mm Ca2+ and fully
      prevented by 10 mm Ca2+. This ameliorative effect was at least partially
      attributed to a less dramatic NaCl-induced membrane depolarization under high
      Ca2+ conditions. Patch-clamp experiments (whole-cell mode) have demonstrated that
      two populations of Ca2+ -sensitive K+ efflux channels exist in protoplasts
      isolated from the mature epidermis of Arabidopsis root and leaf mesophyll cells.
      The instantaneously activating K+ efflux channels showed weak voltage dependence
      and insensitivity to external and internal Na+. Another population of K+ efflux
      channels was slowly activating, steeply rectifying, and highly sensitive to Na+.
      K+ efflux channels in roots and leaves showed different Ca2+ and Na+
      sensitivities, suggesting that these organs may employ different strategies to
      withstand salinity. Our results suggest an additional mechanism of Ca2+ action on
      salt toxicity in plants: the amelioration of K+ loss from the cell by regulating
      (both directly and indirectly) K+ efflux channels.

PMID- 16798943
TI  - Iron deficiency in cyanobacteria causes monomerization of photosystem I trimers
      and reduces the capacity for state transitions and the effective absorption cross
      section of photosystem I in vivo.
AB  - The induction of the isiA (CP43') protein in iron-stressed cyanobacteria is
      accompanied by the formation of a ring of 18 CP43' proteins around the
      photosystem I (PSI) trimer and is thought to increase the absorption cross
      section of PSI within the CP43'-PSI supercomplex. In contrast to these in vitro
      studies, our in vivo measurements failed to demonstrate any increase of the PSI
      absorption cross section in two strains (Synechococcus sp. PCC 7942 and
      Synechocystis sp. PCC 6803) of iron-stressed cells. We report that iron-stressed
      cells exhibited a reduced capacity for state transitions and limited dark
      reduction of the plastoquinone pool, which accounts for the increase in PSII
      related 685 nm chlorophyll fluorescence under iron deficiency. This was
      accompanied by lower abundance of the NADP-dehydrogenase complex and the PSI
      associated subunit PsaL, as well as a reduced amount of phosphatidylglycerol.
      Nondenaturating polyacrylamide gel electrophoresis separation of the chlorophyll
      protein complexes indicated that the monomeric form of PSI is favored over the
      trimeric form of PSI under iron stress. Thus, we demonstrate that the induction
      of CP43' does not increase the PSI functional absorption cross section of whole
      cells in vivo, but rather, induces monomerization of PSI trimers and reduces the
      capacity for state transitions. We discuss the role of CP43' as an effective
      energy quencher to photoprotect PSII and PSI under unfavorable environmental
      conditions in cyanobacteria in vivo.

PMID- 16798944
TI  - Cytosolic triacylglycerol biosynthetic pathway in oilseeds. Molecular cloning and
      expression of peanut cytosolic diacylglycerol acyltransferase.
AB  - Triacylglycerols (TAGs) are the most important storage form of energy for
      eukaryotic cells. TAG biosynthetic activity was identified in the cytosolic
      fraction of developing peanut (Arachis hypogaea) cotyledons. This activity was
      NaF insensitive and acyl-coenzyme A (CoA) dependent. Acyl-CoA:diacylglycerol
      acyltransferase (DGAT) catalyzes the final step in TAG biosynthesis that acylates
      diacylglycerol to TAG. Soluble DGAT was identified from immature peanuts and
      purified by conventional column chromatographic procedures. The enzyme has a
      molecular mass of 41 +/- 1.0 kD. Based on the partial peptide sequence, a
      degenerate probe was used to obtain the full-length cDNA. The isolated gene
      shared less than 10% identity with the previously identified DGAT1 and 2
      families, but has 13% identity with the bacterial bifunctional wax ester/DGAT. To
      differentiate the unrelated families, we designate the peanut gene as AhDGAT.
      Expression of peanut cDNA in Escherichia coli resulted in the formation of
      labeled TAG and wax ester from [14C]acetate. The recombinant E. coli showed high
      levels of DGAT activity but no wax ester synthase activity. TAGs were localized
      in transformed cells with Nile blue A and oil red O staining. The recombinant and
      native DGAT was specific for 1,2-diacylglycerol and did not utilize hexadecanol,
      glycerol-3-phosphate, monoacylglycerol, lysophosphatidic acid, and
      lysophosphatidylcholine. Oleoyl-CoA was the preferred acyl donor as compared to
      palmitoyl- and stearoyl-CoAs. These data suggest that the cytosol is one of the
      sites for TAG biosynthesis in oilseeds. The identified pathway may present
      opportunities of bioengineering oil-yielding plants for increased oil production.

PMID- 16798945
TI  - Enhancement of abscisic acid sensitivity and reduction of water consumption in
      Arabidopsis by combined inactivation of the protein phosphatases type 2C ABI1 and
      HAB1.
AB  - Abscisic acid (ABA) plays a key role in plant responses to abiotic stress,
      particularly drought stress. A wide number of ABA-hypersensitive mutants is
      known, however, only a few of them resist/avoid drought stress. In this work we
      have generated ABA-hypersensitive drought-avoidant mutants by simultaneous
      inactivation of two negative regulators of ABA signaling, i.e. the protein
      phosphatases type 2C (PP2Cs) ABA-INSENSITIVE1 (ABI1) and HYPERSENSITIVE TO ABA1
      (HAB1). Two new recessive loss-of-function alleles of ABI1, abi1-2 and abi1-3,
      were identified in an Arabidopsis (Arabidopsis thaliana) T-DNA collection. These
      mutants showed enhanced responses to ABA both in seed and vegetative tissues, but
      only a limited effect on plant drought avoidance. In contrast, generation of
      double hab1-1 abi1-2 and hab1-1 abi1-3 mutants strongly increased plant
      responsiveness to ABA. Thus, both hab1-1 abi1-2 and hab1-1 abi1-3 were
      particularly sensitive to ABA-mediated inhibition of seed germination.
      Additionally, vegetative responses to ABA were reinforced in the double mutants,
      which showed a strong hypersensitivity to ABA in growth assays, stomatal closure,
      and induction of ABA-responsive genes. Transpirational water loss under drought
      conditions was noticeably reduced in the double mutants as compared to single
      parental mutants, which resulted in reduced water consumption of whole plants.
      Taken together, these results reveal cooperative negative regulation of ABA
      signaling by ABI1 and HAB1 and suggest that fine tuning of ABA signaling can be
      attained through combined action of PP2Cs. Finally, these results suggest that
      combined inactivation of specific PP2Cs involved in ABA signaling could provide
      an approach for improving crop performance under drought stress conditions.

PMID- 16798946
TI  - Effects of endogenous salicylic acid on nodulation in the model legumes Lotus
      japonicus and Medicago truncatula.
AB  - The exogenous addition of salicylic acid (SA) was previously shown to inhibit
      indeterminate but not determinate-type nodulation. We sought to extend these
      results by modulating endogenous levels of SA through the transgenic expression
      of salicylate hydroxylase (NahG) in both stably transformed Lotus japonicus and
      composite Medicago truncatula plants. NahG expression in L. japonicus resulted in
      a marked reduction of SA levels. This reduction correlated with an increase in
      the number of infections and mean nodule number when compared to controls.
      However, a complicating factor was that NahG-expressing plants had greater root
      growth. Spot inoculations of NahG-expressing L. japonicus plants confirmed
      increased nodulation in these plants. Consistent with the reported inhibitory
      effects of exogenous SA on indeterminate-type nodulation, NahG expression in M.
      truncatula plants led to enhanced nodulation and infection. These data point to
      an important role for SA-mediated plant defense pathways in controlling nodule
      formation on both determinate and indeterminate nodule-forming hosts.

PMID- 16798948
TI  - Bestatin, an inhibitor of aminopeptidases, provides a chemical genetics approach
      to dissect jasmonate signaling in Arabidopsis.
AB  - Bestatin, a potent inhibitor of some aminopeptidases, was shown previously to be
      a powerful inducer of wound-response genes in tomato (Lycopersicon esculentum).
      Here, we present several lines of evidence showing that bestatin specifically
      activates jasmonic acid (JA) signaling in plants. First, bestatin specifically
      activates the expression of JA-inducible genes in tomato and Arabidopsis
      (Arabidopsis thaliana). Second, the induction of JA-responsive genes by bestatin
      requires the COI1-dependent JA-signaling pathway, but does not depend strictly on
      JA biosynthesis. Third, microarray analysis using Arabidopsis whole-genome chip
      demonstrates that the gene expression profile of bestatin-treated plants is
      similar to that of JA-treated plants. Fourth, bestatin promotes a series of JA
      related developmental phenotypes. Taken together, the unique action mode of
      bestatin in regulating JA-signaled processes leads us to the hypothesis that
      bestatin exerts its effects through the modulation of some key regulators in JA
      signaling. We have employed bestatin as an experimental tool to dissect JA
      signaling through a chemical genetic screening, which yielded a collection of
      Arabidopsis bestatin-resistant (ber) mutants that are insensitive to the
      inhibitory effects of bestatin on root elongation. Further characterization
      efforts demonstrate that some ber mutants are defective in various JA-induced
      responses, which allowed us to classify the ber mutants into three phenotypic
      groups: JA-insensitive ber mutants, JA-hypersensitive ber mutants, and mutants
      insensitive to bestatin but showing normal response to JA. Genetic and phenotypic
      analyses of the ber mutants with altered JA responses indicate that we have
      identified several novel loci involved in JA signaling.

PMID- 16798947
TI  - Activation of Ntf4, a tobacco mitogen-activated protein kinase, during plant
      defense response and its involvement in hypersensitive response-like cell death.
AB  - Mitogen-activated protein kinase (MAPK) cascades are important signaling modules
      in eukaryotic cells. They function downstream of sensors/receptors and regulate
      cellular responses to external and endogenous stimuli. Recent studies
      demonstrated that SIPK and WIPK, two tobacco (Nicotiana spp.) MAPKs, are involved
      in signaling plant defense responses to various pathogens. Ntf4, another tobacco
      MAPK that shares 93.6% and 72.3% identity with SIPK and WIPK, respectively, was
      reported to be developmentally regulated and function in pollen germination. We
      found that Ntf4 is also expressed in leaves and suspension-cultured cells.
      Genomic analysis excluded the possibility that Ntf4 and SIPK are orthologs from
      the two parental lines of the amphidiploid common tobacco. In vitro and in vivo
      phosphorylation and activation assays revealed that Ntf4 shares the same upstream
      MAPK kinase, NtMEK2, with SIPK and WIPK. Similar to SIPK and WIPK, Ntf4 is also
      stress responsive and can be activated by cryptogein, a proteinaceous elicitin
      from oomycetic pathogen Phytophthora cryptogea. Tobacco recognition of cryptogein
      induces rapid hypersensitive response (HR) cell death in tobacco. Transgenic Ntf4
      plants with elevated levels of Ntf4 protein showed accelerated HR cell death when
      treated with cryptogein. In addition, conditional overexpression of Ntf4, which
      results in high cellular Ntf4 activity, is sufficient to induce HR-like cell
      death. Based on these results, we concluded that Ntf4 is multifunctional. In
      addition to its role in pollen germination, Ntf4 is also a component downstream
      of NtMEK2 in the MAPK cascade that regulates pathogen-induced HR cell death in
      tobacco.

PMID- 16798952
TI  - Associations between prion protein genotype and type traits in East Friesian milk
      sheep.
AB  - Linear models were used to analyse the relationships between the prion protein
      genotypes and the height at the withers and rump, the heart girth and the length
      of the trunk of 440 East Friesian milk sheep. Significant associations were found
      between the ARR allele and the height of the withers and rump, and heart girth.
      The average height at the withers of the homozygous ARR/ARR sheep was 1.9 cm less
      than that of ARQ/ARQ sheep and 1.6 cm less than in sheep heterozygous for ARR;
      the height at the rump, length of the trunk and heart girth were similarly
      smaller. In the ARR/ARR ewes, the average height at the withers was 2.6 cm less
      and the height at the rump was 1.9 cm less than in the ARQ/ARQ ewes.

PMID- 16798950
TI  - L1 division and differentiation patterns influence shoot apical meristem
      maintenance.
AB  - Plant development requires regulation of both cell division and differentiation.
      The class 1 KNOTTED1-like homeobox (KNOX) genes such as knotted1 (kn1) in maize
      (Zea mays) and SHOOTMERISTEMLESS in Arabidopsis (Arabidopsis thaliana) play a
      role in maintaining shoot apical meristem indeterminacy, and their misexpression
      is sufficient to induce cell division and meristem formation. KNOX overexpression
      experiments have shown that these genes interact with the cytokinin, auxin, and
      gibberellin pathways. The L1 layer has been shown to be necessary for the
      maintenance of indeterminacy in the underlying meristem layers. This work
      explores the possibility that the L1 affects meristem function by disrupting
      hormone transport pathways. The semidominant Extra cell layers1 (Xcl1) mutation
      in maize leads to the production of multiple epidermal layers by overproduction
      of a normal gene product. Meristem size is reduced in mutant plants and more
      cells are incorporated into the incipient leaf primordium. Thus, Xcl1 may provide
      a link between L1 division patterns, hormonal pathways, and meristem maintenance.
      We used double mutants between Xcl1 and dominant KNOX mutants and showed that
      Xcl1 suppresses the Kn1 phenotype but has a synergistic interaction with gnarley1
      and rough sheath1, possibly correlated with changes in gibberellin and auxin
      signaling. In addition, double mutants between Xcl1 and crinkly4 had defects in
      shoot meristem maintenance. Thus, proper L1 development is essential for meristem
      function, and XCL1 may act to coordinate hormonal effects with KNOX gene function
      at the shoot apex.

PMID- 16798949
TI  - Imaging of dynamic secretory vesicles in living pollen tubes of Picea meyeri
      using evanescent wave microscopy.
AB  - Evanescent wave excitation was used to visualize individual, FM4-64-labeled
      secretory vesicles in an optical slice proximal to the plasma membrane of Picea
      meyeri pollen tubes. A standard upright microscope was modified to accommodate
      the optics used to direct a laser beam at a variable angle. Under evanescent wave
      microscopy or total internal reflection fluorescence microscopy, fluorophores
      localized near the surface were excited with evanescent waves, which decay
      exponentially with distance from the interface. Evanescent waves with penetration
      depths of 60 to 400 nm were generated by varying the angle of incidence of the
      laser beam. Kinetic analysis of vesicle trafficking was made through an
      approximately 300-nm optical section beneath the plasma membrane using time-lapse
      evanescent wave imaging of individual fluorescently labeled vesicles. Two
      dimensional trajectories of individual vesicles were obtained from the resulting
      time-resolved image stacks and were used to characterize the vesicles in terms of
      their average fluorescence and mobility, expressed here as the two-dimensional
      diffusion coefficient D2. The velocity and direction of vesicle motions, frame-to
      frame displacement, and vesicle trajectories were also calculated. Analysis of
      individual vesicles revealed for the first time, to our knowledge, that two types
      of motion are present, and that vesicles in living pollen tubes exhibit
      complicated behaviors and oscillations that differ from the simple Brownian
      motion reported in previous investigations. Furthermore, disruption of the actin
      cytoskeleton had a much more pronounced effect on vesicle mobility than did
      disruption of the microtubules, suggesting that actin cytoskeleton plays a
      primary role in vesicle mobility.

PMID- 16798953
TI  - Investigations of the reliability of observational gait analysis for the
      assessment of lameness in horses.
AB  - The objectives of this study were to assess the reliability of a numerical rating
      scale (NRS) and a verbal rating scale (VRS) for the assessment of lameness in
      horses and to determine whether they can be used interchangeably. Sixteen
      independent observers graded the severity of lameness in 20 videotaped horses,
      and the agreement between and within observers, correlation and bias were
      determined for each scale. The observers agreed with each other in 56 per cent of
      the observations with the NRS and in 60 per cent of the observations with the
      VRS, and the associated Kendall coefficient of concordance was high. Similar
      trends were evident in the agreement between two observations by each observer.
      The correlation between and within observers was high for both scales. There were
      no significant differences (bias) among the observers' mean scores when using
      either scale. There was a significant correlation between the lameness scores
      attributed when using the two scales, but the differences between the scores when
      plotted against their overall mean were unacceptable for clinical purposes. The
      results indicate that the NRS and VRS are only moderately reliable when used to
      assess lameness severity in the horse, and that they should not be used
      interchangeably.

PMID- 16798954
TI  - Brain and spinal cord haemorrhages associated with Angiostrongylus vasorum
      infection in four dogs.
AB  - Multifocal haemorrhages associated with Angiostrongylus vasorum infection were
      observed in the central nervous system of four dogs with neurological signs
      including depression, seizures, spinal pain and paresis. In magnetic resonance
      images the majority of the lesions were isointense or slightly hyperintense in T1
      weighted images, hyperintense in T2-weighted images and hypointense in T2*
      weighted (gradient echo) images, compatible with haemorrhages more than seven
      days old. Lesions were found in the brain of three of the dogs and in the spinal
      cord of two. The cerebrospinal fluid contained high concentrations of protein and
      evidence of erythrophagia. All the dogs had coagulopathy and pulmonary
      haemorrhage of varying severity. A vasorum larvae were detected in the faeces of
      each of the dogs. Neural A vasorum was confirmed at postmortem examination in two
      dogs.

PMID- 16798955
TI  - Evaluation of clinical signs in suboestrous cows.

PMID- 16798956
TI  - Vertebral epidermoid cyst causing hemiparesis in a dog.

PMID- 16798957
TI  - Multisystemic necrotising vasculitis in a pygmy goat (Capra hircus).

PMID- 16798958
TI  - Incarceration of the small intestine in the epiploic foramen of three calves.

PMID- 16798960
TI  - Oestrus suppression and the NGRC Rules of Racing.

PMID- 16798962
TI  - Promoting the Practice Standards Scheme.

PMID- 16798963
TI  - The battle against infectious diseases in developing countries: the inseparable
      twins of diagnosis and therapy.

PMID- 16798964
TI  - Point: high-sensitivity C-reactive protein and cardiac C-reactive protein assays:
      is there a need to differentiate?

PMID- 16798965
TI  - Counterpoint: Food and Drug Administration guidance for C-reactive protein
      assays: matching claims with performance data.

PMID- 16798966
TI  - Gold-labeled nanoparticle-based immunoresonance scattering spectral assay for
      trace apolipoprotein AI and apolipoprotein B.
AB  - BACKGROUND: Apolipoprotein AI (ApoAI) and ApoB are risk indicators of
      cardiovascular disease. We describe the use of immunoresonance scattering to
      measure the ApoAI and ApoB in serum. METHODS: We used a trisodium citrate method
      to prepare 9.0-nm gold nanoparticles labeled with goat anti-human ApoAI and ApoB
      antibodies. The immune reaction between gold-labeled antibodies and antigens took
      place in Na2HPO4-NaH2PO4 buffer solution (pH 6.4 for ApoAI and pH 6.0 for ApoB)
      in the presence of 75 g/L polyethylene glycol (PEG). We used a transmission
      electron microscope to observe the shape of the gold nanoparticles. Results were
      compared with those obtained by immunoturbidimetric methods. Twenty-five human
      serum samples were assayed by the immunoresonance scattering assay preset with
      the data indicated and by an immunoturbidimetric assay. RESULTS: The presence of
      PEG greatly enhanced the intensity of resonance-scattering peaks at 560 nm. The
      intensity (DeltaI) was proportional to concentration at 0.00833-0.3333 mg/L ApoAI
      and 0.00197-0.1972 mg/L ApoB. The detection limits were 2.04 and 0.96 microg/L
      for ApoAI and ApoB, respectively. The results for human serum samples were in
      agreement with those obtained with an immunoturbidimetric method. Linear
      regression analysis revealed a correlation coefficient, slope, and intercept of
      0.915, 0.966, and 68.53 mg/L, respectively, for ApoAI and 0.919, 0.996, and 15.46
      mg/L for ApoB. CONCLUSION: This method showed high sensitivity and good
      selectivity for quantitative determination of ApoAI and ApoB in human serum, with
      satisfactory results.

PMID- 16798967
TI  - Hyper-gamma-glutamyltransferase is commonly present in non-breast-fed infants
      with biliary atresia successfully treated with portoenterostomy.

PMID- 16798968
TI  - Historical background of the invention of EIA and ELISA.

PMID- 16798970
TI  - Plasma aldosterone assays: comparison between chemiluminescence-based and RIA
      methods.

PMID- 16798971
TI  - Gold-nanoparticle-probe-based assay for rapid and direct detection of
      Mycobacterium tuberculosis DNA in clinical samples.

PMID- 16798972
TI  - Bence Jones cryoglobulinuria: characterization of a urinary kappa light chain
      cryoglobulin.

PMID- 16798973
TI  - Combined locked nucleic acid and molecular beacon technologies for sensitive
      detection of the JAK2V617F somatic single-base sequence variant.

PMID- 16798974
TI  - How accurate is the antiprimer quenching-based real-time PCR for detection of
      Her2/neu in clinical cancer samples?

PMID- 16798975
TI  - LCGreen I-based real-time PCR assays for detecting common ASL and HMGCL variants.

PMID- 16798976
TI  - Survivin and MKI67 mRNA expression in bladder washings of patients with
      superficial urothelial cell carcinoma correlate with tumor stage and grade but do
      not predict tumor recurrence.

PMID- 16798977
TI  - Preanalytic error tracking in a laboratory medicine department: results of a 1
      year experience.

PMID- 16798978
TI  - Multiplex single-color PCR with amplicon melting analysis for identification of
      Aspergillus species.

PMID- 16798979
TI  - Incidence of variant hemoglobin (Hb) and increased fetal Hb concentrations and
      their effect on Hb A1c measurement in a Korean population.

PMID- 16798980
TI  - Preparation of a chimeric armored RNA as a versatile calibrator for multiple
      virus assays.

PMID- 16798981
TI  - Agreement between K-ras sequence variations detected in plasma and tissue DNA in
      pancreatic and colorectal cancer.

PMID- 16798982
TI  - The potential of stem cells in orthopaedic surgery.

PMID- 16798983
TI  - Impaction allografting in revision total hip replacement.

PMID- 16798984
TI  - Does shortening of the first ray in the treatment of adolescent hallux valgus
      prejudice the outcome?

PMID- 16798985
TI  - The use of hydroxyapatite-coated CAD-CAM femoral components in adolescents and
      young adults with inflammatory polyarthropathy: ten-year results.
AB  - Between June 1991 and January 1995, 42 hydroxyapatite-coated CAD-CAM femoral
      components were inserted in 25 patients with inflammatory polyarthropathy, 21 of
      whom had juvenile idiopathic arthritis. Their mean age was 21 years (11 to 35).
      All the patients were reviewed clinically and radiologically at one, three and
      five years. At the final review at a mean of 11.2 years (8 to 13) 37 hips in 23
      patients were available for assessment. A total of four femoral components (9.5%)
      had failed, of which two were radiologically loose and two were revised. The four
      failed components were in patients aged 16 years or less at the time of surgery.
      Hydroxyapatite-coated customized femoral components give excellent medium- to
      long-term results in skeletally-mature young adults with inflammatory
      polyarthropathy. Patients aged less than 16 years at the time of surgery have a
      risk of 28.5% of failure of the femoral component at approximately ten years.

PMID- 16798986
TI  - Acetabular reconstruction with impacted bone allografts and cemented acetabular
      components: a 2- to 13-year follow-up study of 142 aseptic revisions.
AB  - We reviewed the clinical and radiological results of 131 patients who underwent
      acetabular revision for aseptic loosening with impacted bone allograft and a
      cemented acetabular component. The mean follow-up was 51.7 months (24 to 156).
      The mean post-operative Merle D'Aubigne and Postel scores were 5.7 points (4 to
      6) for pain, 5.2 (3 to 6) for gait and 4.5 (2 to 6) for mobility. Radiological
      evaluation revealed migration greater than 5 mm in four acetabular components.
      Radiological failure matched clinical failure. Asymptomatic radiolucent lines
      were observed in 31 of 426 areas assessed (7%). Further revision was required in
      six patients (4.5%), this was due to infection in three and mechanical failure in
      three. The survival rate for the reconstruction was 95.8% (95% confidence
      interval 92.3 to 99.1) overall, and 98%, excluding revision due to sepsis. Our
      study, from an independent centre, has reproduced the results of the originators
      of the method.

PMID- 16798987
TI  - A constrained acetabular component for recurrent dislocation.
AB  - We treated 34 patients with recurrent dislocation of the hip with a constrained
      acetabular component. Roentgen stereophotogrammetric analysis was performed to
      assess migration of the prosthesis. The mean clinical follow-up was 3.0 years
      (2.2 to 4.8) and the radiological follow-up was 2.7 years (2.0 to 4.8). At the
      latest review six patients had died and none was lost to follow-up. There were
      four acetabular revisions, three for aseptic loosening and one for deep
      infection. Another acetabular component was radiologically loose with progressive
      radiolucent lines in all Gruen zones and was awaiting revision. The overall rate
      of aseptic loosening was 11.8% (4 of 34). Roentgen stereophotogrammetric analysis
      in the non-revised components confirmed migration of up to 1.06 mm of translation
      and 2.32 degrees of rotation at 24 months. There was one case of dislocation and
      dissociation of the component in the same patient. Of the 34 patients, 33 (97.1%)
      had no further episodes of dislocation. The constrained acetabular component
      reported in our study was effective in all but one patient with instability of
      the hip, but the rate of aseptic loosening was higher than has been reported
      previously and requires further investigation.

PMID- 16798988
TI  - Alumina ceramic-on-ceramic total hip replacement with a layered acetabular
      component.
AB  - A modular layered acetabular component (metal-polyethylene-ceramic) was developed
      in Japan for use in alumina ceramic-on-ceramic total hip replacement. Between May
      1999 and July 2000, we performed 35 alumina ceramic-on-ceramic total hip
      replacements in 30 consecutive patients, using this layered component and
      evaluated the clinical and radiological results over a mean follow-up of 5.8
      years (5 to 6.5). A total of six hips underwent revision, one for infection, two
      for dislocation with loosening of the acetabular component, two for alumina liner
      fractures and one for component dissociation with pelvic osteolysis. There were
      no fractures of the ceramic heads, and no loosening of the femoral or acetabular
      component in the unrevised hips was seen at final follow-up. Osteolysis was not
      observed in any of the unrevised hips. The survivorship analysis at six years
      after surgery was 83%. The layered acetabular component in our experience, has
      poor durability because of unexpected mechanical failures including alumina liner
      fracture and component dissociation.

PMID- 16798989
TI  - The transverse acetabular ligament: an aid to orientation of the acetabular
      component during primary total hip replacement: a preliminary study of 1000 cases
      investigating postoperative stability.
AB  - Ensuring the accuracy of the intra-operative orientation of the acetabular
      component during a total hip replacement can be difficult. In this paper we
      introduce a reproducible technique using the transverse acetabular ligament to
      determine the anteversion of the acetabular component. We have found that this
      ligament can be identified in virtually every hip undergoing primary surgery. We
      describe an intra-operative grading system for the appearance of the ligament.
      This technique has been used in 1000 consecutive cases. During a minimum follow
      up of eight months the dislocation rate was 0.6%. This confirms our hypothesis
      that the transverse acetabular ligament can be used to determine the position of
      the acetabular component. The method has been used in both conventional and
      minimally-invasive approaches.

PMID- 16798990
TI  - Combined anterior cruciate reconstruction and Oxford unicompartmental knee
      arthroplasty.
AB  - The options for treatment of the young active patient with isolated symptomatic
      osteoarthritis of the medial compartment and pre-existing deficiency of the
      anterior cruciate ligament are limited. The potential longevity of the implant
      and levels of activity of the patient may preclude total knee replacement, and
      tibial osteotomy and unicompartmental knee arthroplasty are unreliable because of
      the ligamentous instability. Unicompartmental knee arthroplasties tend to fail
      because of wear or tibial loosening resulting from eccentric loading. Therefore,
      we combined reconstruction of the anterior cruciate ligament with
      unicompartmental arthroplasty of the knee in 15 patients (ACLR group), and
      matched them with 15 patients who had undergone Oxford unicompartmental knee
      arthroplasty with an intact anterior cruciate ligament (ACLI group). The clinical
      and radiological data at a minimum of 2.5 years were compared for both groups.
      The groups were well matched for age, gender and length of follow-up and had no
      significant differences in their pre-operative scores. At the last follow-up, the
      mean outcome scores for both the ACLR and ACLI groups were high (Oxford knee
      scores of 46 (37 to 48) and 43 (38 to 46), respectively, objective Knee Society
      scores of 99 (95 to 100) and 94 (82 to 100), and functional Knee Society scores
      of 96 and 96 (both 85 to 100). One patient in the ACLR group needed revision to a
      total knee replacement because of infection. No patient in either group had
      radiological evidence of component loosening. The radiological study showed no
      difference in the pattern of tibial loading between the groups. The short-term
      clinical results of combined anterior cruciate ligament reconstruction and
      unicompartmental knee arthroplasty are excellent. The previous shortcomings of
      unicompartmental knee arthroplasty in the presence of deficiency of the anterior
      cruciate ligament appear to have been addressed with the combined procedure. This
      operation seems to be a viable treatment option for young active patients with
      symptomatic arthritis of the medial compartment, in whom the anterior cruciate
      ligament has been ruptured.

PMID- 16798991
TI  - Reconstruction of the anterior cruciate ligament using the polyester ABC ligament
      scaffold: a minimum follow-up of four years.
AB  - We carried out a prospective study of 71 patients who had undergone
      reconstruction of the anterior cruciate ligament with the ABC scaffold. Their
      mean age was 28 years (18 to 50). All had either sub-acute or chronic traumatic
      deficiency of the ligament. The mean period of follow-up was five years (four to
      seven). Assessment included the use of the International Knee Documentation
      Committee score, the modified Lysholm score, the Tegner Activity score, the Knee
      Injury and Osteoarthritis Outcome score and measurement with the KT-1000
      arthrometer. Two patients had mild recurrent synovitis. There were no infections
      and no failures of the ligament. During the period of study, two patients
      sustained a traumatic fracture of a femoral condyle. The implants retained their
      integrity in both cases. All patients returned to their previous or enhanced
      levels of daily activity by three months after operation and 56 (79%) achieved
      their pre-injury level of sporting activity by six months. The patients who were
      competing in National level sports returned to play at one level less after
      operation than before. The Lysholm score showed that 58% of the patients (41)
      were excellent, 34% (24) good, and 8% (6) fair, with a mean post-operative score
      of 93. According to the International Knee Documentation Committee score, 35% of
      knees (25) were 'normal', 52% (37) 'nearly normal' and 13% (9) 'abnormal'.
      Complete satisfaction was noted in 90% of patients (64). The development of
      osteoarthritis and the management of anterior cruciate deficiency associated with
      laxity of the medial collateral ligament remains uncertain. Our results indicate
      that in the medium-term, the ABC ligament scaffold is suitable and effective when
      early and safe return to unrestricted activities is demanded. We acknowledge the
      current general hostility towards reconstruction of the anterior cruciate
      ligament with artificial materials following reports of early failure and chronic
      synovitis associatiated with the production of particulate debris. We did not
      encounter these problems.

PMID- 16798992
TI  - Internal fixation of undisplaced lesions of osteochondritis dissecans in the
      knee.
AB  - A total of 11 patients (12 knees) with stable lesions of osteochondritis
      dissecans of the knee underwent arthroscopic fixation of the fragments using
      polylactide bioabsorbable pins. The site of the lesion was the medial femoral
      condyle in ten knees and the lateral femoral condyle in two. The mean age of the
      patients was 14.8 years (12 to 16). At a mean follow-up of 32.4 months (13 to 38
      months) all fragments had MRI evidence of union. One patient developed early
      transient synovitis, which resolved with non-steroidal anti-inflammatory
      medication. All patients returned to sporting activities within eight months of
      operation and did not require a period of immobilisation.

PMID- 16798993
TI  - A prospective biomechanical study of the association between foot pronation and
      the incidence of anterior knee pain among military recruits.
AB  - Excessive foot pronation has been considered to be related to anterior knee pain.
      We undertook a prospective study to test the hypothesis that exertional anterior
      knee pain is related to the static and dynamic parameters of foot pronation. Two
      weeks before beginning basic training lasting for 14 weeks, 473 infantry recruits
      were enrolled into the study and underwent two-dimensional measurement of their
      subtalar joint displacement angle during walking on a treadmill. Of the 405
      soldiers who finished the training 61 (15%) developed exertional anterior knee
      pain. No consistent association was found between the incidence of anterior knee
      pain and any of the parameters of foot pronation. While a statistically
      significant association was found between anterior knee pain and pronation
      velocity (left foot, p = 0.05; right foot, p = 0.007), the relationship was
      contradictory for the right and left foot. Our study does not support the
      hypothesis that anterior knee pain is related to excessive foot pronation.

PMID- 16798994
TI  - Low tibial osteotomy for varus-type osteoarthritis of the ankle.
AB  - In this retrospective study we have assessed the results of low tibial valgus
      osteotomy for varus-type osteoarthritis of the ankle and its indications. We
      performed an opening wedge osteotomy in 25 women (26 ankles). The mean follow-up
      was for eight years and three months (2 years 3 months to 17 years 11 months). Of
      the 26 ankles, 19 showed excellent or good clinical results. Their mean scores
      for pain, walking, and activities of daily living were significantly improved but
      there was no change in the range of movement. In the ankles which were classified
      radiologically as stage 2 according to our own grading system, with narrowing of
      the medial joint space, and in 11 as stage 3a, with obliteration of the joint
      space at the medial malleolus only, the joint space recovered. In contrast, such
      recovery was seen in only two of 12 ankles classified as stage 3b, with
      obliteration of the joint space advancing to the upper surface of the dome of the
      talus. Low tibial osteotomy is indicated for varus-type osteoarthritis of stage 2
      or stage 3a.

PMID- 16798995
TI  - Arthrodesis versus Mayo resection: the management of the first
      metatarsophalangeal joint in reconstruction of the rheumatoid forefoot.
AB  - In a prospective randomised study 31 patients were allocated to either
      arthrodesis or Mayo resection of the first metatarsophalangeal joint as part of a
      total reconstruction of the rheumatoid forefoot. Of these, 29 were re-examined
      after a mean of 72 months (57 to 80), the Foot Function Index was scored and any
      deformity measured. Load distribution was analysed using a Fscan mat in 14 cases,
      and time and distance were measured in 12 of these patients using a 3D Motion
      system. We found excellent patient satisfaction and a significant, lasting
      reduction of the Foot Function Index, with no statistically significant
      differences between the groups. There were no significant differences in
      recurrence of the deformity, the need for special shoes, gait velocity, step
      length, plantar moment, mean pressure or the position of the centre of force
      under the forefoot. The cadence was higher and the stance phase shorter in the
      fusion group. These results suggest that a Mayo resection may be an equally good
      option for managing the first metatarsophalangeal joint in reconstruction of the
      rheumatoid forefoot.

PMID- 16798996
TI  - Kudo type-5 total elbow arthroplasty in mutilating rheumatoid arthritis: a 5- to
      11-year follow-up.
AB  - We studied 11 patients (14 elbows) with gross rheumatoid deformity of the elbow,
      treated by total arthroplasty using the Kudo type-5 unlinked prosthesis, and who
      were evaluated between five and 11 years after operation. Massive bone defects
      were augmented by autogenous bone grafts. There were no major complications such
      as infection, subluxation or loosening. In most elbows relief from pain and
      stability were achieved. The results, according to the Mayo Elbow Performance
      Score, were excellent in eight, good in five and fair in one. In most elbows
      there was minimal or no resorption of the grafted bone. There were no radiolucent
      lines around the stems of the cementless components. This study shows that even
      highly unstable rheumatoid elbows can be replaced successfully using an unlinked
      prosthesis, with augmentation by grafting for major defects of bone.

PMID- 16798997
TI  - Pedicle subtraction osteotomy for rigid post-tuberculous kyphosis.
AB  - We studied 15 patients with healed tuberculosis of the spine and a resultant
      kyphosis. We selected only those with no neurological deficit and performed a
      wedge resection of the vertebra using a transpedicular approach. The wedge was
      removed from the apex of the deformity. For those with a neurological deficit, we
      chose the conventional anterior debridement and decompression with 360 degrees
      circumferential fusion. At a mean follow-up of 26.8 months (8 to 46) the outcome
      was good with an increase in the mean Oswestry Disability Index from 56.26 (48 to
      62) pre-operatively to 11.2 (6 to 16) at the latest follow-up.

PMID- 16798998
TI  - Management of complex tibial and femoral nonunion using the Ilizarov technique,
      and its cost implications.
AB  - We reviewed 78 femoral and tibial nonunions treated between January 1992 and
      December 2003. Of these, we classified 41 in 40 patients as complex cases because
      of infection (22), bone loss (6) or failed previous surgery (13). The complex
      cases were all treated with Ilizarov frames. At a mean time of 14.1 months (4 to
      38), 39 had healed successfully. Using the Association for the Study and
      Application of the Methods of Ilizarov scoring system we obtained 17 excellent,
      14 good, four fair and six poor bone results. The functional results were
      excellent in 14 patients, good in 14, fair in two and poor in two. A total of six
      patients were lost to follow-up and two had amputations so were not evaluated for
      final functional assessment. All but two patients were very satisfied with the
      results. The average cost of treatment to the treating hospital was approximately
      pound 30,000 per patient. We suggest that early referral to a tertiary centre
      could reduce the morbidity and prolonged time off work for these patients. The
      results justify the expense, but the National Health Service needs to make
      financial provision for the reconstruction of this type of complex nonunion.

PMID- 16798999
TI  - A Dega-type osteotomy after closure of the triradiate cartilage in non-walking
      patients with severe cerebral palsy.
AB  - A total of 47 non-walking patients (52 hips) with severe cerebral palsy and with
      a mean age of 14 years, (9 to 27) underwent a Dega-type pelvic osteotomy after
      closure of the triradiate cartilage, together with a derotation varus-shortening
      femoral osteotomy and soft-tissue correction for hip displacement which caused
      pain and/or difficulties in sitting. The mean follow-up was 48 months (12 to
      153). The migration percentage improved from a pre-operative mean of 70% (26% to
      100%) to 10% (0% to 100%) post-operatively. In five hips the post-operative
      migration percentage was greater than 25%, which was associated with continuing
      pain in two patients. Three patients had persistent hip pain and a migration
      percentage less than 25%. In five hips a fracture through the acetabulum
      occurred, and in another there was avascular necrosis of the superior acetabular
      segment, but these had no adverse effect on functional outcome. We conclude that
      it is possible to perform a satisfactory pelvic osteotomy of this type in these
      patients after the triradiate cartilage has been closed.

PMID- 16799000
TI  - The results of limb lengthening by callus distraction using an extending
      intramedullary nail (Fitbone) in non-traumatic disorders.
AB  - Limb lengthening by callus distraction and external fixation has a high rate of
      complications. We describe our experience using an intramedullary nail (Fitbone)
      which contains a motorised and programmable sliding mechanism for limb
      lengthening and bone transport. Between 2001 and 2004 we lengthened 13 femora and
      11 tibiae in ten patients (seven men and three women) with a mean age of 32 years
      (21 to 47) using this nail. The indications for operation were short stature in
      six patients and developmental or acquired disorders in the rest. The mean
      lengthening achieved was 40 mm (27 to 60). The mean length of stay in hospital
      was seven days (5 to 9). The mean healing index was 35 days/cm (18.8 to 70.9).
      There were no cases of implant-related infection or malunion.

PMID- 16799002
TI  - The Thompson hemiarthroplasty: a new problem for an old favourite.
AB  - The Thompson hemiarthroplasty is a popular hip prosthesis. We present two case
      reports highlighting a significant alteration in the design of the implant which
      compromised the success of the operations. In recent years the manufacturing
      process of this prosthesis has changed, with a resultant increase in the volume
      of the stem of 10 ml. It is essential that manufacturers inform orthopaedic
      surgeons of any alteration in the design of the implant and supply compatible
      instrumentation to minimise surgical errors. Surgeons must remain vigilant when
      checking the compatibility of the trial and definitive prostheses.

PMID- 16799001
TI  - The incidence of deep prosthetic infections in a specialist orthopaedic hospital:
      a 15-year prospective survey.
AB  - The Control of Infection Committee at a specialist orthopaedic hospital
      prospectively collected data on all episodes of bacteriologically-proven deep
      infection arising after primary hip and knee replacements over a 15-year period
      from 1987 to 2001. There were 10 735 patients who underwent primary hip or knee
      replacement. In 34 of 5947 hip replacements (0.57%) and 41 of 4788 knee
      replacements (0.86%) a deep infection developed. The most common infecting micro
      organism was coagulase-negative staphylococcus, followed by Staphylococcus
      aureus, enterococci and streptococci. Of the infecting organisms, 72% were
      sensitive to routine prophylactic antimicrobial agents. Of the infections, 29%
      (22) arose in the first three months following surgery, 35% between three months
      and one year (26), and 36% (27) after one year. Most cases were detected early
      and treated aggressively, with eradication of the infection in 96% (72). There
      was no significant change in the infection rate or type of infecting micro
      organism over the course of this study. These results set a benchmark, and
      importantly emphasise that only 64% of peri-prosthetic infections arise within
      one year of surgery. These results also illustrate the advantages of conducting
      joint replacement surgery in the isolation of a specialist hospital.

PMID- 16799003
TI  - Total hip replacement in a patient with systemic mastocytosis: a case report.
AB  - Systemic mastocytosis is a rare condition that often involves the bone marrow. We
      report the case of a patient with systemic mastocytosis who underwent total hip
      replacement. Technical difficulties encountered during the procedure included a
      narrow medullary canal and abnormally hard bone, later confirmed by laboratory
      measurements. Follow-up at five years showed a good clinical and radiological
      outcome.

PMID- 16799004
TI  - Synchronous bifocal alveolar rhabdomyosarcoma: a case report.
AB  - We report a case of bifocal rhabdomyosarcoma involving the hand and thigh in an
      11-year-old female. We highlight the importance of a thorough clinical
      examination and an aggressive surgical approach in which each lesion is treated
      as a separate primary.

PMID- 16799005
TI  - A comparison of two biomaterial carriers for osteogenic protein-1 (BMP-7) in an
      ovine critical defect model.
AB  - Critical size defects in ovine tibiae, stabilised with intramedullary
      interlocking nails, were used to assess whether the addition of
      carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant
      would affect the implant's efficacy for bone regeneration. The biomaterial
      carriers were a 'putty' carrier of carboxymethylcellulose and bovine-derived type
      I collagen (OPP) or the standard with collagen alone (OPC). These two treatments
      were also compared to "ungrafted" negative controls. Efficacy of regeneration was
      determined using radiological, biomechanical and histological evaluations after
      four months of healing. The defects, filled with OPP and OPC, demonstrated
      radiodense material spanning the defect after one month of healing, with
      radiographic evidence of recorticalisation and remodelling by two months. The OPP
      and OPC treatment groups had equivalent structural and material properties that
      were significantly greater than those in the ungrafted controls. The structural
      properties of the OPP- and OPC-treated limbs were equivalent to those of the
      contralateral untreated limb (p > 0.05), yet material properties were inferior (p
      < 0.05). Histopathology revealed no residual inflammatory response to the
      biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85%
      lamellar bone within the defect, and less than 25% of the regenerate was composed
      of fibrous tissue. The defects in the untreated control animals contained less
      than 40% lamellar bone and more than 60% was fibrous tissue, creating full
      cortical thickness defects. In our studies carboxymethylcellulose did not
      adversely affect the capacity of the standard OP-1 implant for regenerating bone.

PMID- 16799006
TI  - Urinary excretion of deoxypyridinoline in Perthes' disease: a prospective,
      controlled comparative study in 83 children.
AB  - Our aim was to investigate the relationship between urinary excretion of
      deoxypyridinoline (DPD) as a marker of bone resorption, and Perthes' disease.
      There were 39 children with Perthes' disease in the florid stage who collected
      first-morning urine samples at regular intervals of at least three months. The
      level of urinary DPD was analysed by chemiluminescence immunoassay and was
      correlated with the radiological stage of the disease as classified by
      Waldenstrom, and the severity of epiphyseal involvement according to the
      classification systems of Catterall and Herring. The urinary DPD levels of a
      group of 44 healthy children were used as a control. The median urinary
      DPD/creatinine (CREA) ratio was significantly reduced (p < 0.0001) in the
      condensation stage and increased to slightly elevated values at the final stage
      (p = 0.05) when compared with that of the control group. Herring-C patients
      showed significantly lower median DPD/CREA ratios than Herring-B patients (p =
      0.03). The significantly decreased median DPD/CREA ratio in early Perthes'
      disease indicated a reduced bone turnover and supports the theory of a systemic
      aetiology. Urinary levels of DPD may therefore be used to monitor the course of
      Perthes' disease.

PMID- 16799007
TI  - Computer navigation of the acetabular component: a cadaver reliability study.
AB  - Our aim was to assess the intra- and inter-observer reliability in the
      establishment of the anterior pelvic plane used in imageless computer-assisted
      navigation. From this we determined the subsequent effects on version and
      inclination of the acetabular component. A cadaver model was developed with a
      specifically-designed rod which held the component tracker at a fixed orientation
      to the pelvis, leaving the anterior pelvic plane as the only variable. Eight
      surgeons determined the anterior pelvic plane by palpating and registering the
      bony landmarks as reference points. The exact anterior pelvic plane was then
      established by using anatomically-placed bone screws as reference points. The
      difference between the surgeons was found to be highly significant (p < 0.001).
      The variation was significantly larger for anteversion (sd 9.6 degrees ) than for
      inclination (sd 6.3 degrees ). The present method for registering pelvic
      landmarks shows significant inaccuracy, which highlights the need for improved
      methods of registration before this technique is considered to be safe.

PMID- 16799008
TI  - Movement patterns of the C-stem femoral components: an RSA study of 33 primary
      total hip arthroplasties followed for two years.

PMID- 16799009
TI  - Declining availability of human eye tissues for research.

PMID- 16799011
TI  - Morphological classification of parvalbumin-containing retinal ganglion cells in
      mouse: single-cell injection after immunocytochemistry.
AB  - PURPOSE: Matching the neuron's morphology with its expression of a particular
      protein cannot be easily achieved by immunocytochemistry alone, as many proteins
      are expressed too weakly. In this study, a newly developed method was adopted to
      match mouse retinal ganglion cell (RGC) morphology with its expression of
      parvalbumin. METHODS: Parvalbumin-containing ganglion cells were first identified
      by immunocytochemistry and then were iontophoretically injected with a lipophilic
      dye DiI. Then confocal microscopy was used to characterize the morphologic
      classification of the parvalbumin-immunoreactive (IR) ganglion cells on the basis
      of the dendritic field size, branching pattern, and stratification within the
      inner plexiform layer. RESULTS: The results indicate that at least eight
      different types of ganglion cells express parvalbumin in the mouse retina. They
      were heterogeneous in morphology: monostratified to bistratified, small-to-large
      dendritic field size, and sparse-to-dense dendritic arbors. CONCLUSIONS: Single
      cell injection, after immunocytochemistry, provided the first means to identify
      the detailed functional anatomy of parvalbumin-containing RGCs in the mouse
      retina. The combined approach of cell morphology and the selective expression of
      parvalbumin will not only provide useful data for further correlation of
      physiological properties of the RGCs, but it will also provide a useful strategy
      for matching a neuron's morphology with its expression of a particular protein.

PMID- 16799010
TI  - Detection of the bcl-2 t(14;18) translocation and proto-oncogene expression in
      primary intraocular lymphoma.
AB  - PURPOSE: Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma
      that initially infiltrates the retina, vitreous, or optic nerve head, with or
      without central nervous system involvement. This study examined the expression of
      the bcl-2 t(14;18) translocation, the bcl-10 gene, and high expression of bcl-6
      mRNA in PIOL cells. METHODS: Microdissection and PCR analysis were used to
      examine vitreous specimens in patients with PIOL for the presence of bcl-2
      t(14;18) translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A medical
      record review was also conducted to determine whether the bcl-2 t(14;18)
      translocation correlated with prognosis. RESULTS: Forty of 72 (55%) PIOL patients
      expressed the bcl-2 t(14;18) translocation at the major breakpoint region.
      Fifteen of 68 (22%) patients expressed the translocation at the minor cluster
      region. The bcl-10 gene was detected in 6 of 26 (23%) patients, whereas 4 of 4
      (100%) PIOL patients expressed higher levels of bcl-6 mRNA compared with
      inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL patients
      revealed no significant association between bcl-2 t(14;18) translocations and
      survival or relapse. However, patients with the translocation were significantly
      younger. CONCLUSIONS: PIOL has unique molecular patterns of bcl-2, bcl-10, and
      bcl-6 when compared with other systemic lymphomas. This study lays the foundation
      for future studies aimed at exploring the genotypic classification of PIOL based
      on the quantitative molecular framework of gene expression profiling, with the
      goal of providing useful adjuncts to the pathologic diagnosis of this complex
      disease.

PMID- 16799012
TI  - Histone deacetylase activity regulates apaf-1 and caspase 3 expression in the
      developing mouse retina.
AB  - PURPOSE: Apoptosis is a form of programmed cell death essential for both tissue
      development and maintenance of tissue homeostasis. Apoptosis protease activating
      factor (Apaf)-1 and caspase 3 are downregulated in the retina during postnatal
      development. The decreased expression of these genes is potentially a critical
      survival strategy adopted to protect against accidental cell death. The purpose
      of this study was to investigate the transcriptional mechanism involved in the
      downregulation of Apaf-1 and caspase 3. METHODS: SDS-polyacrylamide gel
      electrophoresis and semiquantitative PCR were used to examine Apaf-1 and caspase
      3 expression levels during development. TdT-mediated dUTP nick-end labeling
      (TUNEL) and DNA laddering were used to identify cells undergoing apoptosis.
      RESULTS: A decrease in expression of Apaf-1 and caspase 3 during retinal
      development correlated with a decreased susceptibility to an apoptotic stimulus.
      Furthermore, treatment with a histone deacetylase (HDAC) inhibitor, trichostatin
      A (TSA), resulted in widespread hyperacetylation in the retina, coinciding with
      transcriptional activation of Apaf-1 and caspase 3 and subsequent induction of
      apoptosis in postnatal day (P)5 and P15 retinas. However, inhibition of HDAC
      activity is not sufficient to induce apoptosis in the mature retina (P60).
      CONCLUSIONS: Overall, these results elicit the conclusion that downregulation of
      Apaf-1 and caspase 3 in the developing retina correlates with a decreased
      susceptibility to apoptotic stimuli and ensures the survival of the retina.
      Furthermore, the authors propose that, in the early postnatal retina, HDAC
      activity governs the transcriptional regulation of these genes. Upregulation of
      Apaf-1 and caspase 3 coincides with an induction of apoptosis. In the mature
      retina transcriptional activation of these genes or induction of apoptosis was
      not observed.

PMID- 16799013
TI  - Myopia, axial length, and OCT characteristics of the macula in Singaporean
      children.
AB  - PURPOSE: The purpose of this study was to evaluate the associations between
      macular volume and thickness, as assessed by optic coherence tomography (OCT),
      with refraction and axial length (AL) in children. METHODS: A total of 104
      Chinese school children (51 girls and 53 boys) 11 to 12 years of age were
      randomly selected from one school during the 2005 examination in the Singapore
      Cohort Study of the Risk Factors for Myopia (SCORM). Cycloplegic autorefraction
      was performed to obtain refraction (defined as spherical equivalent [SE]) and
      ultrasound biometry performed to obtain the AL. Macular volume and thickness were
      then measured (StratusOCT3; Carl Zeiss Meditec, Dublin, CA). RESULTS: Children
      with moderate myopia (SE at least -3.0 D) tended to have smaller total macular
      volume and thinner quadrant-specific macular thickness (except in the inferior
      and superior inner quadrants), followed by children with low myopia (-0.5<or=SE<
      3.0 D), compared with children with no myopia (SE>-0.5 D). Total macular volume
      was positively associated with SE (beta=1.58, 95% CI, 0.84 to 2.32, standardized
      beta=0.14, P<0.001) and negatively associated with AL (beta=-1.20, 95% CI, -1.62
      to -0.79, standardized beta=0.45, P<0.001) in multiple linear regression models
      controlling for age and gender. CONCLUSIONS: In children, increasing axial myopia
      was associated with reduced macular volume and thickness. These findings suggest
      that early anatomic changes may be present in the retinas of children with axial
      myopia.

PMID- 16799014
TI  - Prevalence and clinical characteristics of glaucoma in adult Chinese: a
      population-based study in Liwan District, Guangzhou.
AB  - PURPOSE: To assess the prevalence and mechanism of glaucoma in adults living in
      an urban area of southern China. METHODS: Random clustering sampling was used to
      identify adults aged 50 years and over in Liwan District, Guangzhou. Glaucoma was
      diagnosed with the ISGEO (International Society of Geographical and
      Epidemiological Ophthalmology) classification scheme. All subjects underwent
      gonioscopy. RESULTS: In the study, 1504 subjects (75.3% participation rate) were
      examined, with a crude prevalence of all glaucoma of 3.8% (95% confidence
      interval [CI], 2.8%-4.8%). Primary open-angle glaucoma (POAG) was found in 2.1%
      (95% CI, 1.4%-2.8%) and primary angle-closure glaucoma (PACG) in 1.5% (95% CI,
      0.8%-2.1%). The prevalence of all glaucoma was significantly higher in older
      people and men. CONCLUSIONS: POAG was more common than PACG in this southern
      Chinese population, with rates similar to those reported in Chinese Singaporeans.
      The age-adjusted rate of POAG was similar to that found in European-derived
      populations, but PACG was more common among Chinese, indicating that there is a
      large burden of glaucoma in the Chinese people.

PMID- 16799015
TI  - The Contact Lens Impact on Quality of Life (CLIQ) Questionnaire: development and
      validation.
AB  - PURPOSE: To develop and validate a questionnaire for the measurement of the
      impact of contact lenses on quality of life (QoL): The Contact Lens Impact on
      Quality of Life (CLIQ) Questionnaire. METHODS: The questionnaire was developed
      and validated using conventional methods and Rasch analysis to assure content
      validity, repeatability, construct validity, and low respondent burden. Item
      identification and selection (647 items) were performed with an extensive
      literature review, professional advice, and lay focus groups. Item reduction used
      focus groups and data obtained from 161 subjects completing a 90-item pilot
      questionnaire. Validity and reliability, from data of 128 additional subjects,
      were assessed using Rasch analysis, intraclass correlation coefficient, and Bland
      Altman limits of agreement. RESULTS: A 28-item CLIQ Questionnaire was developed
      and shown to have good validity and reliability by Rasch analysis statistics:
      real person separation, 2.02; model person separation, 2.17; reliability, 0.80;
      root mean square measurement error, 2.73; mean square+/-SD infit, 1.01+/-0.18;
      outfit, 1.01+/-0.19. The items (mean score, 49.8+/-4.9) were well targeted to the
      subjects (mean score, 51.2+/-6.2) with a mean difference of 1.35 (scale range, 0
      100) units. Test-retest intraclass correlation coefficient (0.86) and coefficient
      of repeatability (+/-8.00 units) demonstrated good repeatability. CONCLUSIONS:
      Rasch analysis and standard psychometric analyses demonstrated that the 28-item
      CLIQ Questionnaire is a valid and reliable measure of QoL in contact lens
      wearers. A scoring algorithm is provided for CLIQ Questionnaire users to convert
      raw scores into the Rasch analysis-derived linear person measures.

PMID- 16799016
TI  - Perceived barriers to care and attitudes about vision and eye care: focus groups
      with older African Americans and eye care providers.
AB  - PURPOSE: To identify by using focus group methods the perceived barriers to eye
      care and attitudes about vision and eye care among older African Americans as
      well as among ophthalmologists and optometrists serving their communities.
      METHODS: Seventeen focus groups of older African Americans residing in the
      Birmingham or Montgomery, Alabama, areas were led by an experienced facilitator.
      Discussion was stimulated by a semistructured script focused on their perceived
      barriers to eye care and attitudes about vision and eye care. Six focus groups of
      ophthalmologists and optometrists who practiced in this geographic region
      addressed the same topics. Discussion was audiotaped and transcribed. Comments
      were coded using a multistep content analysis protocol. RESULTS: One hundred
      nineteen African Americans (age range, 59-97 years) and 35 eye care providers
      (51% ophthalmologists, 49% optometrists) participated. The barrier-to-care
      problem most frequently cited by both African Americans and eye care providers
      was transportation. The next most common problems mentioned by African Americans
      were trusting the doctor, communicating with the doctor, and the cost of eye
      care; and for eye care providers, the next most common problems were cost, trust,
      and insurance. With respect to older African Americans' comments on their
      attitudes about vision and eye care, these comments were predominantly positive
      (69%), highlighting the importance of eye care and behavior in their lives and
      attitudes that facilitated care. However, when eye care providers relayed their
      impressions of African Americans' attitudes about vision and eye care, their
      comments were largely negative (74%) centering on concerns and frustrations that
      older African Americans did not have attitudes or engage in behavior that
      facilitate eye care. CONCLUSIONS: These results provide some guidance for the
      design of interventions to increase the use of routine eye care in this
      population. At a societal level, there is a need for affordable and accessible
      transportation services for older African Americans seeking eye care. For
      ophthalmologists, optometrists, and their staffs, there is a need for continuing
      education that imparts culturally sensitive and age-appropriate communication and
      trust-building skills for interactions with this population. In addition to
      reinforcing the generally positive attitudes of older African Americans toward
      the importance of eye care, community-based educational programs should be
      focused on strategies for overcoming the common barriers to care.

PMID- 16799017
TI  - In vivo corneal confocal microscopy comparison of intralase femtosecond laser and
      mechanical microkeratome for laser in situ keratomileusis.
AB  - PURPOSE: To assess and compare corneal modifications induced by IntraLase
      PulsionFS femtosecond laser and mechanical microkeratome Hansatome for laser in
      situ keratomileusis (LASIK) using the new-generation Heidelberg Retina Tomograph
      II (HRT II)/Rostock Cornea Module confocal microscope. METHODS: In this case
      control study, 24 eyes of 12 patients were examined with the HRT II in the follow
      up of IntraLase femtosecond laser for LASIK myopic surgery. Twenty eyes of 10
      patients were also examined after microkeratome Hansatome-LASIK surgery. In both
      groups, the patients underwent the first follow-up examination on day 7 and the
      last 12 months after surgery. Morphologic modifications of corneal architecture
      were evaluated, and comparisons were made between the two flap-formation
      techniques. RESULTS: Evaluation of both groups on day 7 showed keratocyte
      transformation, most likely related to cellular activation beneath the interface.
      The flap margin after the IntraLase technique appeared microscopically as a clear
      cut edge that included the epithelial plug. At month 2, secondary fibrosis,
      adjacent to the still well-defined IntraLase flap edge, was observed. This
      reaction diminished with time, leaving a fibrotic scar adjacent to a wound
      constriction originating from the surrounding stroma. The flap margin of the
      mechanical microkeratome had the appearance of a less clearly identified fibrotic
      scar with no epithelial plug. CONCLUSIONS: This study reveals morphologic
      similarities between the interfaces obtained by femtosecond laser and mechanical
      microkeratome, probably because the same excimer laser performed the
      photoablation. However, the IntraLase flap margin showed greater fibrotic
      scarring than that induced by the mechanical microkeratome.

PMID- 16799018
TI  - Fluoroquinolone eye drop-induced cytotoxicity: role of preservative in P2X7 cell
      death receptor activation and apoptosis.
AB  - PURPOSE: To investigate in vitro whether eye toxicity is attributable to the
      preservative or the fluoroquinolone used in ophthalmic formulations. METHODS:
      Corneal and conjunctival cell lines were incubated with preserved (benzalkonium
      chloride [BAC]) or unpreserved ofloxacin solutions for 15 minutes. Several
      concentrations of BAC were also tested (0.0025%-0.01%). Membrane integrity,
      reactive oxygen species, and superoxide anion production were assessed with the
      neutral red test, the 2',7'-dichlorofluorescein diacetate test, and the
      dihydroethidium test, respectively. P2X7 cell death receptor activation was
      evaluated using the YO-PRO-1 assay and apoptosis (chromatin condensation and
      translocation of phosphatidylserine) using the Hoechst 33342 and annexin V-FITC
      dyes. Tests were performed with microplate cytofluorometry, inverted fluorescence
      microscopy, and flow cytometry. RESULTS: The preserved solution and all tested
      BAC concentrations induced a significant decrease in membrane integrity, unlike
      the unpreserved ofloxacin. Reactive oxygen species and superoxide anion
      productions observed for all solutions were significantly higher for the
      preserved ofloxacin and BAC solutions, which also induced apoptosis (chromatin
      condensation and translocation of phosphatidylserine) through P2X7 pore opening,
      whereas unpreserved ofloxacin did not. CONCLUSIONS: The cytotoxicity observed
      with fluoroquinolone eye drops seems to be caused mainly by the preservative,
      which induced P2X7 cell death receptor activation associated with oxidative
      stress and apoptosis. Therefore, it is recommended that fluoroquinolone be used
      in preservative-free formulations.

PMID- 16799019
TI  - No VSX1 gene mutations associated with keratoconus.
AB  - PURPOSE: To determine whether mutations of the VSX1 gene play a pathogenetic role
      in the development of keratoconus (KTCN). METHODS: DNA extraction, PCR
      amplification, and direct sequencing of the VSX1 gene were performed in 100
      unrelated patients with diagnoses of clinical and topographic features of KTCN.
      RESULTS: Of the four previously identified presumed pathogenic mutations in the
      VSX1 gene (Leu17Pro, Asp144Glu, Leu159Met, and Arg166Trp), only Asp144Glu was
      identified in a single affected patient. Two novel single nucleotide
      polymorphisms (SNPs), both resulting in synonymous substitutions, were
      identified: c.53G>T (Ser6Ser) in four affected patients and c.209G>T (Pro58Pro)
      in two affected patients. Two previously reported SNPs were also identified:
      c.426C>A (Arg131Ser) in one affected patient and c.581A>G (Ala182Ala) in 51 of
      the 100 affected patients. CONCLUSIONS: Only one of the presumed pathogenic
      mutations in the VSX1 gene, Asp144Glu, was identified in a single member of the
      cohort of affected patients. However, as previously demonstrated, Asp144Glu is a
      non-disease-causing polymorphism. The absence of pathogenic mutations in the VSX1
      gene in a large number of unrelated KTCN patients indicates that other genetic
      factors are involved in the development of this disorder.

PMID- 16799020
TI  - Laser scanning in vivo confocal microscopy of the normal human corneoscleral
      limbus.
AB  - PURPOSE: To elucidate the structure of the human corneoscleral limbus by in vivo
      laser scanning confocal microscopy and to correlate limbal epithelial dimensions
      and density with the central epithelium and in relation to age. METHODS: Fifty
      adult subjects were recruited into one of two age groups: younger (age<45 years)
      and older (age>or=45 years). Fifty left eyes of these 50 healthy subjects were
      examined by laser scanning in vivo confocal microscopy, to assess the basal
      epithelium of the central cornea and inferior limbus. Mean epithelial cell
      diameter, area, and density were calculated for the central basal epithelium,
      limbus-corneal basal epithelium, and limbus-palisade epithelium. RESULTS: Data
      were analyzed in relation to the two age groups, group A, 30+/-6 years (n=25;
      mean+/-SD), and group B, 60+/-11 years (n=25; P<0.01). Mean epithelial density in
      the limbus-cornea and limbus-palisade regions decreased significantly with age:
      limbus-cornea group A=7253+/-1077 cells/mm2 group B=6614+/-987 cells/mm2, P=0.03;
      limbus palisade group A=5409+/-799 cells/mm2, group B=5055+/-722 cells/mm2,
      P=0.03). Central corneal epithelial density did not change with age: group
      A=6162+/-503 cells/mm2, group B=6362+/-614 cells/mm2, P=0.08. Mean epithelial
      density was greatest at the limbus-cornea (7010+/-1081 cells/mm2) and lowest at
      the limbus-palisades (5289+/-847 cells/mm2). The mean width of palisade ridges
      was 25.0+/-6.3 microm. CONCLUSIONS: This is the first study to image clearly the
      living human corneal limbus by laser scanning in vivo confocal microscopy and to
      demonstrate quantitative changes in the basal epithelium with age.

PMID- 16799021
TI  - Femtosecond laser-assisted corneal flap cuts: morphology, accuracy, and
      histopathology.
AB  - PURPOSE: Precision in corneal flap cutting is essential in LASIK surgery. Current
      mechanical microkeratomes have a very good performance record; however, in a few
      cases, complications can occur during the microkeratome pass and flap cut.
      Femtosecond lasers offer an alternative to the mechanical cut and can provide
      additional features regarding the flap morphology. In this study, we analyzed
      femtosecond laser flaps regarding their morphology, cut accuracy, and
      histopathology. METHODS: Forty-five fresh porcine cadaveric eyes were prepared
      for femtosecond laser flap cutting with the Femtec femtosecond laser system
      (20/10 Perfect Vision, Heidelberg, Germany). The eyes were assigned to three
      different thickness groups, with 120-, 140-, or 180-microm cut depth,
      respectively. In addition, different flap diameters ranging from 8.0 to 9.5 mm
      and rim edge angulations between 60 degrees and 90 degrees were performed. After
      the cut, the eyes were examined under a microscope regarding accuracy and
      potential defects, and flap thickness and diameter were measured. In addition,
      flaps were prepared for further histopathologic examination. RESULTS: All flap
      cuts were easily performed without any intraoperative complications. Flap
      thickness measurements revealed a median (in micrometers) of 110.5 (intended
      thickness 120), 142.5 (intended 140), and 180.0 (intended 180), respectively. The
      flap diameter for an intended size between 8.0 and 9.5 mm was within a range of
      +/-0.4 mm, the median at the maximum was 0.3 mm off. Histopathology revealed very
      low to almost no changes in the stromal structure of the cornea and correct hinge
      angulations. CONCLUSIONS: LASIK flap cuts were easily performed without any
      complications. The accuracy and morphology were very precise and consistent.
      Histopathology revealed a smooth cut with hinge angulations, as expected.

PMID- 16799022
TI  - SRC-family tyrosine kinases in wound- and ligand-induced epidermal growth factor
      receptor activation in human corneal epithelial cells.
AB  - PURPOSE: The authors have previously demonstrated that wounding of human corneal
      epithelial cells (HCECs) transactivates epidermal growth factor (EGF) receptor
      (EGFR) and its downstream signaling pathways and that this EGFR signaling is
      required for epithelial wound healing. In this study, the authors sought to
      identify the underlying mechanisms for EGFR transactivation in response to
      wounding in HCECs. METHODS: SV40-immortalized HCEC (THCE) monolayer was wounded
      and allowed to heal in the presence or absence of a selective inhibitor of the
      Src family kinases PP2 and EGFR ligand heparin-binding EGF-like growth factor (HB
      EGF). Wound closure was monitored by photographing of the injury immediately or
      24 hours after wounding. Activation of EGFR in THCE cells and in primary HCECs
      was analyzed by immunoprecipitation of EGFR, followed by Western blotting with
      phosphotyrosine antibody. Phosphorylation of extracellular signal-regulated
      kinase (ERK), AKT (a major substrate of phosphatidylinositol 3'-kinase [PI3K]),
      Src at tyrosine Y416, and EGFR at Y845 was analyzed by Western blotting with
      antibodies specific to phosphorylated proteins. Effects of PP2 on THCE cell
      migration were determined by Boyden chamber migration assay. RESULTS: Among
      several inhibitors tested, PP2 blocked wound-induced EGFR phosphorylation in THCE
      cells. PP2 at 12.5 microM effectively inhibited EGFR transactivation in response
      to wounding and to the phosphorylation of ERK and AKT in THCE cells and primary
      HCECs. Consistent with the inhibition of EGFR transactivation, PP2 also
      attenuated epithelial migration and wound closure with or without exogenously
      added HB-EGF. PP2 at a concentration as high as 50 microM exhibited no effects on
      HB-EGF induced ERK phosphorylation. On the other hand, AKT phosphorylation was
      much more sensitive to PP2 than ERK or EGFR phosphorylation because 3.13 microM
      PP2 effectively inhibited wound- or HB-EGF-induced AKT phosphorylation.
      CONCLUSIONS: These results suggest that Src kinase mediates wound-induced EGFR
      transactivation and participates in a pathway to activate the PI3K-AKT pathway
      downstream of EGFR in HCECs.

PMID- 16799023
TI  - Development of a three-dimensional organ culture model for corneal wound healing
      and corneal transplantation.
AB  - PURPOSE: To develop and evaluate a three-dimensional organ culture system of the
      cornea anterior chamber that could replicate the in vivo processes occurring
      during corneal wound healing and corneal transplantation. METHODS: Bovine
      corneoscleral buttons were clamped in a specially designed chamber through the
      sclera outside the limbus. The epithelium was exposed to air, and its anterior
      surface was automatically irrigated. The endothelial layer was perfused
      separately with media under normal intraocular pressure. Wound healing and
      corneal transplantation were observed using light, scanning, and transmission
      electron microscopy. RESULTS: The organ culture system maintained the epithelium,
      the putative epithelial stem cells in the limbus, the stroma, and the endothelium
      in good condition for the 10-day period during which the system was evaluated.
      The authors observed that the processes of wound healing and corneal
      transplantation in the model appeared similar to those occurring in vivo.
      CONCLUSIONS: In vitro model closely replicated the in vivo processes of wound
      healing and corneal transplantation. The authors believe this model will be
      useful for basic investigations into the cornea, such as study of the response of
      the cornea to surgery, wound healing, toxins, and therapeutic agents.

PMID- 16799024
TI  - Apical corneal barrier disruption in experimental murine dry eye is abrogated by
      methylprednisolone and doxycycline.
AB  - PURPOSE: To evaluate the mechanism of apical corneal epithelial barrier
      disruption in response to experimental ocular surface desiccation and the effects
      of two anti-inflammatory agents (methylprednisolone and doxycycline) on this
      process. METHODS: Experimental dry eye (EDE) was created in C57BL/6 mice, without
      or with topical therapy, 1% methylprednisolone, 0.025% doxycycline, or
      physiologic saline solution (PSS) four times per day. Corneal smoothness and
      Oregon green dextran (OGD) permeability were assessed. Desquamation of and
      cornified envelope protein (involucrin and small proline-rich protein [SPRR]-2)
      expression by the corneal epithelium was evaluated by laser scanning confocal
      microscopy. Levels of cornified envelope proteins mRNA were measured by real-time
      PCR. RESULTS: Corneal OGD permeability, surface irregularity, and the number of
      desquamating apical corneal epithelia significantly increased in EDE. Desiccating
      stress significantly increased expression of involucrin and SPRR-2 in the corneal
      epithelia. Treatment of EDE with methylprednisolone or doxycycline reduced
      corneal permeability to OGD, improved corneal smoothness, and decreased
      involucrin and SPRR-2 immunoreactivity compared with EDE+PSS. CONCLUSIONS:
      Disruption of apical corneal epithelial barrier function in dry eye is
      accompanied by increased apical desquamation and increased expression of
      cornified envelope proteins. Topical treatment of EDE with the anti-inflammatory
      agents methylprednisolone or doxycycline preserves apical corneal barrier
      function.

PMID- 16799025
TI  - Inhibition of matrix metalloproteinase-3 synthesis in human conjunctival
      fibroblasts by interleukin-4 or interleukin-13.
AB  - PURPOSE: Fibroproliferative lesions of the conjunctiva known as giant papillae
      are a characteristic of vernal keratoconjunctivitis (VKC). The abundance of T
      helper 2 (Th2) cells and cytokines is increased in the giant papillae and tear
      fluid of individuals with VKC, and the Th2 cytokines interleukin (IL)-4 and IL-13
      each stimulate the production of extracellular matrix (ECM) proteins by
      conjunctival fibroblasts. The role of Th2 cytokines in the development of giant
      papillae was further examined by determination of the effects of these molecules
      on the production by conjunctival fibroblasts of matrix metalloproteinase (MMP)
      3, a key enzyme in ECM degradation. METHODS: The amount of MMP-3 released into
      the culture medium by human conjunctival fibroblasts was determined by enzyme
      linked immunosorbent assay, and the intracellular abundance of MMP-3 mRNA was
      quantitated by reverse transcription and real-time polymerase chain reaction
      analysis. Signaling by the transcription factors NF-kappaB and AP-1 was evaluated
      by immunoblot and immunofluorescence analyses. RESULTS: Of the Th2 cytokines
      tested, only IL-4 and -13 inhibited both the basal and IL-1beta-induced release
      of MMP-3 by conjunctival fibroblasts. These effects of IL-4 and -13 were
      inhibited by neutralizing antibodies to the IL-4 receptor complex. IL-4 and -13
      also each reduced the basal abundance, as well as inhibited the IL-1beta-induced
      upregulation, of MMP-3 mRNA in these cells. Neither IL-4 nor -13 affected the IL
      1beta-induced activation of NF-kappaB or the AP-1 component c-Jun. CONCLUSIONS:
      IL-4 and -13 each inhibit MMP-3 synthesis in human conjunctival fibroblasts,
      suggesting that these Th2 cytokines may contribute to the excessive deposition of
      ECM in giant papillae by preventing matrix degradation mediated by this enzyme.

PMID- 16799026
TI  - Eye movement recordings as an effectiveness indicator of gene therapy in RPE65
      deficient canines: implications for the ocular motor system.
AB  - PURPOSE: To perform ocular motility recordings of infantile nystagmus (IN) in
      RPE65-deficient canines and determine whether they can be used as a motor
      indicator of restored retinal function to investigate the effects of gene
      therapy. METHODS: Treated and untreated canines were comfortably suspended in a
      custom-built sling and encouraged to fixate on distant targets at gaze angles
      varying between +/-15 degrees horizontally and +/-10 degrees vertically. Ocular
      motility recordings were made, using two distinct methods-infrared reflection and
      high-speed video. The resultant recordings from three untreated, four treated,
      and three pre- and post-treatment dogs were analyzed for using the eXpanded
      Nystagmus Acuity Function (NAFX), which yields an objective assessment of best
      potential visual acuity, based on the duration and repeatable accuracy of
      foveation and centralisation. RESULTS: During fixation, the untreated dogs
      exhibited large-amplitude, classic IN waveforms, including pendular and jerk in
      both the horizontal and vertical planes, which prevented them from keeping the
      targets within the area centralis (the region of highest receptor density,
      spanning +/-3 degrees horizontally by +/-1.5 degrees vertically, analogous to the
      fovea). Some untreated dogs also had small-amplitude (0.5-1 degrees), high
      frequency (6-9 Hz) oscillations. Under the same conditions, successfully treated
      canines no longer exhibited clinically detectable IN. Their IN was converted to
      waveforms with very low amplitudes that yielded higher NAFX values and allowed
      target images to remain well within the area centralis. Of note, uniocular
      treatment appeared to damp the IN in both eyes. Behaviorally, the treated dogs
      were able to successfully navigate through obstacles more easily without
      inadvertent contact, a task beyond the untreated dogs' ability. CONCLUSIONS: Gene
      therapy that successfully restored retinal function also reduced the accompanying
      IN to such a great extent that it was not clinically detectable approximately 90%
      of the time in many of the dogs. IN improvement, as quantified by the NAFX, is an
      objective motor indicator of visual improvement due to gene therapy.

PMID- 16799027
TI  - Effects of orthoptic treatment on the CA/C and AC/A ratios in convergence
      insufficiency.
AB  - PURPOSE: To evaluate the effect of orthoptic treatment on the AC/A (A,
      accommodation; C, convergence) and CA/C ratios in subjects with convergence
      insufficiency (CI). METHODS: The change in AC/A and CA/C ratios after a 12-week
      period of home-based orthoptic treatment was examined in 10 subjects (mean age,
      25.4+/-4.1 years [SD]). Both the AC/A and CA/C ratios were measured by using
      gradient response methods. For the AC/A ratio, the gradient phoria method was
      used, and for the CA/C ratio the prism-induced change in accommodation was
      measured with a refractometer. RESULTS: No change in the AC/A and CA/C ratios
      (P>0.05) were found after orthoptic treatment. However, improvements were found
      (P<0.05) in the fast and slow vergence mechanisms. CONCLUSIONS: Despite
      improvements in the fast and slow vergence mechanisms no change was found in the
      AC/A and CA/C ratios after orthoptic treatment in CI subjects. This finding is
      unexpected in light of the present understanding of CI, and an alternative theory
      is proposed.

PMID- 16799028
TI  - Interaction between ocular stabilization reflexes in patients with whiplash
      injury.
AB  - PURPOSE: In the past few decades, the automobile has become an increasingly more
      popular means of transport, which has led to an increasing number of rear-end
      collisions and consequently has resulted in more patients with whiplash
      associated disorders (WADs). Recently, it was found that the gain of one of the
      ocular stabilization reflexes-the cervico-ocular reflex (COR)-is elevated in
      patients with whiplash injury. The COR responds to proprioceptive signals from
      the neck and acts in conjunction with the vestibulo-ocular reflex (VOR) and the
      optokinetic reflex (OKR) to preserve stable vision on the retina during head
      motion. Therefore, an investigation was conducted to determine whether the
      reported elevation of the COR in WADs is accompanied by changes in VOR or OKR.
      METHODS: Eye movements of 13 patients and 18 age-matched healthy controls were
      recorded with an infrared eye-tracking device. RESULTS: Analysis confirmed a
      significant increase in COR gain in whiplash patients. Meanwhile the VOR and OKR
      gains remained the same. No correlation was found between the gains of the
      reflexes in individual patients. This is in contrast to earlier observations in
      elderly subjects and subjects with labyrinthine defects, who showed increases in
      COR gain and decreases in VOR gain. CONCLUSIONS: Impaired neck motion, altered
      proprioception of the neck, or disorganization in the process of VOR plasticity
      could explain the lack of change in VOR gain.

PMID- 16799029
TI  - Views of glaucoma patients on aspects of their treatment: an assessment of
      patient preference by conjoint analysis.
AB  - PURPOSE: To determine by conjoint analysis which factors in the management and
      treatment of glaucoma were of most importance to patients and to relate these
      factors to the patient's clinical glaucoma condition. METHODS: An interview-based
      study was performed. Demographic and visual function data are recorded.
      Participants completed the Visual Function Questionnaire-25 and ranked 10
      hypothetical patient scenarios that contained different risks of moderate visual
      loss, postoperative complications, long-term blindness, use of topical
      medication, and glaucoma surgery. Conjoint analysis was performed to determine
      the relative importance of these factors for individuals and the group as a
      whole. RESULTS: Eighty-two patients were interviewed from two consultants'
      outpatient clinics. Forty-five were male and 37 female. Seventy-nine were white.
      The most important factors to patients with glaucoma were the risk of moderate
      visual impairment and the risk of blindness, with an importance of 38% and 27%,
      respectively. The use of topical medication had an importance of 11%. Proceeding
      to surgical intervention (trabeculectomy) had an importance of 15%, and the small
      risk of visual deterioration after surgery (trabeculectomy) had an importance of
      9%. CONCLUSIONS: To patients, the most important factors regarding glaucoma and
      its treatment are the risks of moderate visual loss (the ability to continue to
      drive) and long-term blindness. The treatment methods used are of much less
      importance.

PMID- 16799030
TI  - Structure-function relationships using confocal scanning laser ophthalmoscopy,
      optical coherence tomography, and scanning laser polarimetry.
AB  - PURPOSE: To assess the strength of the association between retinal nerve fiber
      layer (RNFL) thickness and optic disc topography measured with confocal retinal
      tomography (HRT II; Heidelberg Engineering, Dossenheim, Germany), optical
      coherence tomography (StratusOCT; Carl Zeiss Meditec, Inc., Dublin, CA), and
      scanning laser polarimetry (GDx with variable corneal compensator, VCC; Carl
      Zeiss Meditec, Inc.), and visual field (VF) sensitivity and to determine whether
      this association is better expressed as a linear or nonlinear function. METHODS:
      One hundred twenty-seven patients with glaucoma or suspected glaucoma and 127
      healthy eyes from enrollees in the Diagnostic Innovations in Glaucoma Study
      (DIGS) were tested on HRT II, StratusOCT, GDx VCC, and standard automated
      perimetry (SAP, with the Swedish Interactive Thresholding Algorithm [SITA])
      within 3 months of each other. Linear and logarithmic associations between RNFL
      thickness (HRT II, StratusOCT, and GDx VCC) and neuroretinal rim area (HRT II)
      and SAP sensitivity expressed in decibels were determined globally and for six
      RNFL/optic disc regions (inferonasal, inferotemporal, temporal, superotemporal,
      superonasal, and nasal) and six corresponding VF regions (superior, superonasal,
      nasal, inferonasal, inferior, and temporal). RESULTS: The associations (R2)
      between global and regional RNFL/optic disc measurements and VF sensitivity
      ranged from <0.01 (temporal RNFL, nasal VF, and nasal RNFL, temporal VF; linear
      and logarithmic associations) to 0.26 (inferotemporal RNFL, superonasal VF;
      logarithmic association) for HRT II; from 0.02 (temporal RNFL, nasal VF; linear
      association) to 0.38 (inferotemporal RNFL, superonasal VF; logarithmic
      association) for OCT; and from 0.03 (temporal RNFL, nasal VF; linear association)
      to 0.21 (inferotemporal RNFL, superonasal VF; logarithmic association) for GDx.
      Structure-function relationships generally were strongest between the
      inferotemporal RNFL-optic disc sector and the superonasal visual field and were
      significantly stronger for StratusOCT RNFL thickness than for other instruments
      in this region. Global associations (linear and logarithmic) were significantly
      stronger using OCT compared with HRT. In most cases, logarithmic fits were not
      significantly better than linear fits when visual sensitivity was expressed in
      log units (i.e., decibels). CONCLUSIONS: These results suggest that structure
      function associations are strongest with StratusOCT measurements and are similar
      between HRT II and GDx VCC and these associations are generally no better
      expressed logarithmically than linearly when healthy, suspect, and glaucomatous
      eyes are considered.

PMID- 16799031
TI  - Pointwise linear regression analysis for detection of visual field progression
      with absolute versus corrected threshold sensitivities.
AB  - PURPOSE: To compare the performance of point-wise linear regression analysis
      (PLR) with total deviation (TD) versus corrected or pattern deviation (PD)
      threshold sensitivities for detection of visual field progression. METHODS: Four
      hundred two eyes (402 patients) enrolled in the Advanced Glaucoma Intervention
      Study (AGIS) were selected. Criteria for progression according to PLR were a
      slope<or=-1 dB/year with P<or=0.01 with >or=2 worsening points within the same
      Glaucoma Hemifield Test cluster. PLR was performed on TD and PD threshold
      sensitivities and compared to clinical evaluation. Eyes were classified into
      three groups based on mean deviation (MD): mild (MD>or=-6 dB), moderately
      advanced (-6 dB>MD>or=-12 dB), and advanced (MD<-12 dB) glaucoma. RESULTS: Visual
      field progression was observed in 154 (38%), 85 (21%), and 175 (44%) eyes,
      according to PLR(TD) and PLR(PD), and clinical evaluation. The pair-wise
      agreement between clinicians and PLR(TD) was significantly greater than that of
      clinicians and PLR(PD) (kappa=0.48, 95% CI: 0.44-0.52 vs. kappa=0.31, 95% CI:
      0.27-0.35). Agreement between PLR(TD) and PLR(PD) decreased with increasing
      glaucoma severity: kappa (95% CI)=0.60 (0.52-0.67), 0.41 (0.35-0.47), and 0.33
      (0.27-0.40) for mild, moderately advanced, and advanced glaucoma, respectively.
      CONCLUSIONS: Point-wise linear regression analysis on TD threshold sensitivities
      performed better than the same analysis on PD when clinical evaluation was used
      as a reference. Agreement between the two methods was less in moderately advanced
      and advanced glaucoma.

PMID- 16799032
TI  - Optic disc and visual field progression in ocular hypertensive subjects:
      detection rates, specificity, and agreement.
AB  - PURPOSE: To examine the detection rates, specificity, and agreement between
      visual field (VF) progression and Heidelberg Retina Tomograph (HRT; Heidelberg
      Engineering, GmbH, Heidelberg, Germany) rim area (RA) progression in subjects
      with ocular hypertension (OHT). METHODS: One hundred ninety-eight OHT and 21
      control subjects were examined prospectively (1994-2001) with regular Humphrey VF
      (Carl Zeiss Meditec, Inc., Dublin, CA) and HRT testing. Point-wise linear
      regression (PLR) of sensitivity/time was used to assess VF progression, using
      standard and three-omitting (less stringent and stringent) criteria. The change
      in HRT-detected progression was assessed by linear regression of sectoral
      RA/time, defined as slope>1%/year, with significance level tailored according to
      series variability. Less stringent and stringent criteria were tested.
      Specificity was estimated by the proportions of control subjects with disease
      progression and significantly improving subjects (all). Agreement between disc
      and field progression in the subjects with OHT was assessed with specificities
      matched for both VF and HRT. RESULTS: Specificity for VF PLR was estimated to be
      85.7% to 95.4% when standard criteria were used, and for RA/time to be 88.1% to
      90.5% with the less-stringent criteria. In this comparison, 21.2% progressed by
      RA alone and 20.2% by VF alone, and 12.1% progressed by both RA and VF.
      Specificity was estimated to be 95.2% to 98.2% for both VF PLR and RA/time, using
      the three-omitting criteria and the stringent RA/time criteria, respectively. In
      this comparison, 8.6% progressed by RA alone, 15.1% by VF alone, and 3.5% by both
      RA and VF. CONCLUSIONS: A relatively high frequency of detected disease
      progression was observed with either method, with progression by VF occurring at
      least as frequently as progression by RA. Poor agreement between RA and VF
      progression was observed regardless of the specificity of the progression
      criteria. The results indicate that, in patients with ocular hypertension,
      monitoring of both VF and optic disc is necessary, as agreement between optic
      disc and VF progression is the exception rather than the rule.

PMID- 16799033
TI  - In vivo imaging and quantitative evaluation of the rat retinal nerve fiber layer
      using scanning laser ophthalmoscopy.
AB  - PURPOSE: To determine whether scanning laser ophthalmoscopy (SLO) is useful for
      in vivo imaging and quantitative evaluation of rat retinal nerve fiber layer
      (RNFL) using an optic nerve crush model. METHODS: The optic nerve of the right
      eye was crushed intraorbitally with a clip. The left eye served as the untreated
      control. Fundus images of both eyes were recorded by SLO using an argon blue
      laser before and 1, 2, and 4 weeks after optic nerve crush. The focused plane was
      sequentially moved by changing the refractive values in the SLO setting. The
      range of refractive values (DeltaF) in which the RNFL reflex was clearly observed
      was determined. The RNFL thickness in retinal sections was measured and compared
      to the DeltaF value from SLO images taken before histologic preparation. RESULTS:
      Striations of RNFL radiating from the optic disc were clearly visible by SLO. No
      obvious changes in the RNFL reflex were observed 1 week after optic nerve crush.
      However, striations of RNFL became uniformly darker and thinner 2 weeks after the
      crush and were barely visible 4 weeks after the crush. The DeltaF value was
      unchanged 1 week after the crush, but then decreased significantly and
      progressively after the second week. DeltaF was unchanged in the control eyes
      during the experimental period. The DeltaF value correlated significantly with
      the histologically determined RNFL thickness. CONCLUSIONS: SLO is a useful and
      valuable tool for in vivo imaging and quantitative evaluation of rat RNFL.

PMID- 16799034
TI  - Effects of topical hypotensive drugs on circadian IOP, blood pressure, and
      calculated diastolic ocular perfusion pressure in patients with glaucoma.
AB  - PURPOSE: To compare the short-term effects of timolol 0.5%, brimonidine 0.2%,
      dorzolamide 2%, and latanoprost 0.005% on intraocular pressure (IOP), blood
      pressure (BP), and diastolic ocular perfusion pressure (DOPP), calculated as the
      difference between the diastolic blood pressure (DBP) and IOP. METHODS: According
      to a 4 x 4 Latin squares design for repeated measures, 27 untreated patients and
      patients with newly diagnosed primary open-angle glaucoma (POAG) were treated
      with timolol 0.5% at 8 AM and 8 PM; brimonidine 0.2% at 8 AM and 8 PM;
      dorzolamide 2% at 8 AM, 2 PM, and 8 PM; and latanoprost 0.005% at 8 PM. The
      duration of each treatment course was 6-weeks, with a 4-week washout between each
      treatment. IOP and BP were measured at baseline and at the end of each treatment
      period. IOP was measured every 2 hours throughout a 24-hour period. Sitting IOP
      was measured from 8 AM to 10 PM by Goldmann applanation tonometry. Supine IOP was
      assessed from 12 to 6 AM by means of a handheld electronic tonometer (TonoPen XL;
      Mentor, Norwell, MA). BP monitoring was performed by means of an automated
      portable device (TM-2430; A & D Co., Saitama, Japan). RESULTS: All the drugs
      tested decreased the IOP significantly at all time points in comparison with
      baseline pressure. The mean 24-hour IOP after latanoprost administration (16.62+/
      0.98 mm Hg) was significantly lower than that after timolol, brimonidine, or
      dorzolamide (P=0.0001). During the 24-hour period, brimonidine induced a
      significant decrease in systolic BP (SBP) and DBP at all time points when
      compared with baseline measurements and with those after administration of the
      other drugs (P<0.0001). Timolol caused a significant decrease in DBP and SBP at
      all the 24-hour time points when compared with the baseline and with the
      dorzolamide- and latanoprost-induced changes (P<0.0001). The mean 24-hour DOPPs
      were 50.7+/-5.9 mm Hg at baseline, 53+/-5.5 mm Hg with timolol, 46.2+/-5.4 mm Hg
      with brimonidine, 55.9+/-4.6 mm Hg with dorzolamide, and 56.4+/-4.9 mm Hg with
      latanoprost. Brimonidine induced a significant decrease in the mean 24-hour DOPP
      compared with that at baseline (P<0.0001), whereas dorzolamide and latanoprost
      induced a significant increase (P<0.0001). CONCLUSIONS: Latanoprost seemed to
      induce a uniform reduction in IOP during the 24-hour period, although timolol was
      as effective as latanoprost during the daytime, and dorzolamide are as effective
      as latanoprost at night. SBP and DBP were significantly decreased by either
      timolol or brimonidine. In this study of patients with newly diagnosed POAG, only
      dorzolamide and latanoprost significantly increased mean 24-hour DOPP.

PMID- 16799035
TI  - Effect of heparin II domain of fibronectin on actin cytoskeleton and adherens
      junctions in human trabecular meshwork cells.
AB  - PURPOSE: To determine whether the heparin II (HepII) domain of fibronectin
      previously shown to increase outflow facility affects the formation and assembly
      of actin cytoskeleton and adherens junctions in human trabecular meshwork (HTM)
      cells. METHODS: Normal HTM cells and two transformed HTM cell lines were treated
      for 24 hours with increasing concentrations of the HepII domain. Disruptions in
      adherens junctions and the actin cytoskeleton were determined using
      immunofluorescence microscopy and Western blot analysis of immunoprecipitated
      cadherin/catenin complexes. Actin filaments were detected with phalloidin.
      Catenin (alpha and beta) and cadherin antibodies were used to detect adherens
      junctions. RESULTS: Treatments of cultures with the HepII domain caused
      cadherin/beta-catenin complexes in adherens junctions and actin filaments to
      disassemble. The disruption of adherens junctions and actin filaments occurred in
      a dose-dependent and temporal fashion. The disassembly of actin filaments
      occurred first, followed by the disassembly of adherens junctions. Dissociation
      of adherens junctions, but not actin filaments, was reversible if the HepII
      domain was removed. Reassembly of actin filaments required the addition of serum.
      Serum, however, could not trigger the reassembly of actin filaments if the HepII
      domain was present, suggesting that the HepII domain acted downstream of the
      serum stimulated RhoA activity. CONCLUSIONS: The exposure of HTM cells to the
      HepII domain triggers the disassembly of actin filaments and the subsequent
      destabilization of adherens junctions in HTM cells. This suggests that the HepII
      domain may increase outflow facility in cultured anterior segments by altering
      the organization of the TM cytoarchitecture.

PMID- 16799036
TI  - Interleukin-6 protects retinal ganglion cells from pressure-induced death.
AB  - PURPOSE: The response of retinal ganglion cells (RGCs) to ocular pressure in
      glaucoma likely involves signals from astrocytes and microglia. How glia-derived
      factors influence RGC survival at ambient and elevated pressure and whether the
      inflammatory cytokine interleukin-6 (IL-6) is a contributing factor were
      investigated. METHODS: Primary cultures of retinal astrocytes, microglia, and
      RGCs were prepared using immunomagnetic separation. Comparisons were made of RGC
      survival at ambient and elevated pressure (+70 mm Hg) and with pressure
      conditioned medium from glia with, and depleted of, IL-6. RESULTS: Pressure
      elevated for 24 to 48 hours reduced RGC density, increased TUNEL labeling, and
      upregulated several apoptotic genes, including the early immediate genes c-jun
      and jun-B. Pressure-conditioned medium from astrocytes reduced RGC survival
      another 38%, while microglia medium returned RGC survival to ambient levels.
      These effects were unrelated to IL-6 in microglia medium. Neither astrocyte- nor
      microglia-conditioned medium affected ambient RGC survival unless depleted of IL
      6, which induced a 63% and a 18% decrease in RGCs, respectively. Recombinant IL-6
      equivalent to levels in glia-conditioned medium doubled RGC survival at elevated
      pressure. CONCLUSIONS: For RGCs at ambient pressure, IL-6 secreted from
      astrocytes and microglia under pressure is adequate to abate other proapoptotic
      signals from these glia. For RGCs challenged by elevated pressure, decreased IL-6
      in astrocyte medium is insufficient to counteract these signals. Increased IL-6
      in microglia medium counters not only proapoptotic signals from these cells but
      also the pressure-induced apoptotic cascade intrinsic to RGCs.

PMID- 16799037
TI  - In vivo imaging and counting of rat retinal ganglion cells using a scanning laser
      ophthalmoscope.
AB  - PURPOSE: To determine whether a scanning laser ophthalmoscope (SLO) is useful for
      in vivo imaging and counting of rat retinal ganglion cells (RGCs). METHODS: RGCs
      of Brown Norway rats were retrogradely labeled bilaterally with the fluorescent
      dye 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodine (DiA). The
      unilateral optic nerve was crushed intraorbitally with a clip. RGCs were imaged
      in vivo with an SLO with an argon blue laser (488 nm) and optical filter sets for
      fluorescein angiography, before and 1, 2, and 4 weeks after the crush.
      Fluorescent cells were also counted in retinal flatmounts at baseline and 1, 2,
      and 4 weeks after the crush. An image overlay analysis was performed to check
      cell positions in the SLO images over time. Lectin histochemical analysis was
      performed to determine the relationship of microglia to the newly emerged DiA
      fluorescence detected by image overlay analysis after the optic nerve crush.
      RESULTS: Fluorescent RGCs were visible in vivo with an SLO. RGC survival
      decreased gradually after the crush. In the retina after the optic nerve crush,
      newly emerged DiA fluorescence detected by image overlay analysis corresponded to
      fluorescent cells morphologically different from RGCs in the retinal flatmount
      and was colocalized mostly with lectin-stained microglial processes. RGC counts
      by SLO were comparable to those in retinal flatmounts. CONCLUSIONS: The SLO is
      useful for in vivo imaging of rat RGCs and therefore may be a valuable tool for
      monitoring RGC changes over time in various rat models of RGC damage.

PMID- 16799038
TI  - Melanopsin-expressing retinal ganglion cells are more injury-resistant in a
      chronic ocular hypertension model.
AB  - PURPOSE: To investigate the survival of melanopsin-expressing retinal ganglion
      cells (mRGCs) after the induction of chronic ocular hypertension. METHODS:
      Intraocular pressure (IOP) was elevated in adult Sprague-Dawley rats using an
      argon laser to photocoagulate the episcleral and limbal veins. IOP was measured
      with a calibrated tonometer and monitored for a period. Seven days before the
      animals were killed, a piece of sterile foam soaked with gold fluorescent dye was
      placed onto the superior colliculus (SC) to label the SC-projecting retinal
      ganglion cells (scRGCs) retrogradely. mRGCs were visualized by free floating
      immunohistochemistry on whole-mounted retinas. The number of surviving scRGCs and
      mRGCs were counted on flatmounted retinas. The branching pattern of dendrites and
      soma size of mRGCs were examined. RESULTS: An approximately 1.7-fold increase of
      IOP and a significant loss of scRGCs were found in experimental eyes after laser
      photocoagulation. However, no significant cell loss or morphologic changes on
      mRGCs and their dendrites after the induction of chronic ocular hypertension are
      noticed over a 12-week period. CONCLUSIONS: Although the degeneration of retinal
      ganglion cells (RGCs) is a major concern in glaucomatous damage, the findings
      show that mRGCs are less susceptible to death after the induction of chronic
      ocular hypertension. This result indicates that mRGCs carry some unique
      properties that are different from those of other subpopulations of RGCs. The
      immunohistochemistry approach can be used to distinguish easily these mRGCs from
      other subtypes. This method provides a useful tool to investigate their injury
      resistant properties that are informative for the development of effective
      neuroprotective treatment for glaucoma.

PMID- 16799039
TI  - Macrophages are vital in spontaneous intraocular tumor eradication.
AB  - PURPOSE: Injection of tumor cells transformed by the early region 1 of human
      adenovirus type 5 (Ad5E1) in the anterior chamber (AC) of C57BL/6 mice leads to
      intraocular tumor formation. This tumor disappears spontaneously 3 to 4 weeks
      after tumor inoculation without damaging the neighboring ocular tissues. Previous
      studies have shown that CD4+ T cells, IFNgamma, and TRAIL (tumor necrosis factor
      related apoptosis-inducing ligand) play a role in the spontaneous eradication of
      this particular intraocular tumor. This study was conducted to determine whether
      macrophages are involved in the natural elimination of this intraocular tumor.
      METHODS: Ad5E1-expressing tumor cells were inoculated into the AC of syngeneic
      C57BL/6 mice. Macrophage depletion was obtained by subconjunctival (scj),
      subcutaneous (sc), or intravenous (iv) injection of clodronate liposomes 2, 8,
      and 14 days after tumor inoculation. Control C57BL/6 mice received PBS liposomes
      at similar time points after tumor injection or were left untreated. The presence
      of macrophages in the AC tumor was determined with the macrophage marker F4/80.
      RESULTS: Progressive tumor growth was observed in mice that were
      subconjunctivally depleted of macrophages, whereas spontaneous tumor eradication
      occurred in all other groups. F4/80 staining was negative in the AC tumors of
      mice treated scj with clodronate liposomes in contrast to the positive F4/80
      staining in the tumors of the other groups. Ad5E1 tumor antigen still reached the
      tumor-draining lymph nodes (DLNs) of mice locally depleted for macrophages.
      CONCLUSIONS: Local macrophages in the eye are involved in the process of
      spontaneous AC tumor eradication in mice. However, it is not conclusive from
      these data exactly how tumor-specific CD4+ T cells and macrophages interact with
      each other to eliminate the Ad5E1-AC tumor without any collateral eye damage.

PMID- 16799040
TI  - A CX3CR1 genotype associated with retinal vasculitis in patients in the United
      Kingdom.
AB  - PURPOSE: To investigate whether polymorphisms in the gene encoding the chemokine
      receptor CX3CR1, which has been linked to changes in functional ligand-binding
      activity, are associated with retinal vasculitis (RV) in a cohort of patients in
      the United Kingdom. METHODS: DNA was prepared from whole blood of 126 patients
      with RV and 95 healthy individuals by a standard salting-out procedure. Two
      polymorphisms, V249I and T280M, were analyzed by multiplex polymerase chain
      reaction-sequence-specific primers (PCR-SSPs). RESULTS: There was no significant
      difference between the prevalence of V249 or I249 variants in patients with RV or
      in control subjects. By contrast, the 280M variant was significantly raised in
      patients compared with control subjects (P=0.01), the IV/MT haplotype was also
      more prevalent in patients with RV than in control subjects (P=0.006), and the
      I249/M280 haplotype was associated with retinal vasculitis (P=0.01). The 280M
      variant was significantly associated with the nonischemic form of RV compared
      with healthy control subjects (P=0.009). CONCLUSIONS: Polymorphisms related to a
      functional decrease in ligand binding activity of CX3CR1 are associated with
      disease in U.K. patients with retinal vasculitis. CX3CR1 and its ligand CX3CL1
      have been implicated in leukocyte adhesion and neuronal protection. Changes in
      the activity of this interaction may have a role in the pathogenesis of RV.

PMID- 16799041
TI  - Biofilm formation by Staphylococcus epidermidis on intraocular lens material.
AB  - PURPOSE: To compare biofilm formation by Staphylococcus epidermidis on different
      intraocular lens (IOL) materials. METHODS: The S. epidermidis strains, ATCC 12228
      (American Type Culture Collection) and ATCC 35984 (biofilm-producer) were used.
      Biofilms were cultivated on disks of different IOL materials: silicone, PMMA
      (polymethylmethacrylate), acrylic, or MPC (2-methacryloyloxyethyl
      phosphorylcholine) surface-modified acrylic. Biofilms were stained with crystal
      violet (CV) which served as an index of biofilm formation. The bacterial
      population was enumerated after biofilm homogenization. Biofilms were also
      examined by scanning electron microscopy (SEM). RESULTS: Among the four materials
      tested, the least amount of biofilm formed on silicone. Biofilm production was
      significantly different between acrylic and MPC surface-modified acrylic lenses
      at 48 hours (P<0.05-0.01). The bacterial populations were significantly different
      between acrylic and silicone over 72 hours (P<0.05-0.01). The population on
      acrylic and MPC surface-modified acrylic continued to increase over 72 hours. The
      biofilm was recognized after a 24-hour incubation. Rates of biofilm-positive SEM
      fields, which were defined as being occupied by biofilm over at least half of the
      area, were significantly different between acrylic and silicone at 72 hours
      (P<0.05-0.01). CONCLUSIONS: S. epidermidis formed biofilm most intensely on
      acrylic among the four IOL materials tested. MPC surface-modified acrylic has a
      preventive effect on biofilm formation.

PMID- 16799042
TI  - Accommodative lens refilling in rhesus monkeys.
AB  - PURPOSE: Accommodation can be restored to presbyopic human eyes by refilling the
      capsular bag with a soft polymer. This study was conducted to test whether
      accommodation, measurable as changes in optical refraction, can be restored with
      a newly developed refilling polymer in a rhesus monkey model. A specific intra-
      and postoperative treatment protocol was used to minimize postoperative
      inflammation and to delay capsular opacification. METHODS: Nine adolescent rhesus
      monkeys underwent refilling of the lens capsular bag with a polymer. In the first
      four monkeys (group A) the surgical procedure was followed by two weekly
      subconjunctival injections of corticosteroids. In a second group of five monkeys
      (group B) a treatment intended to delay the development of capsular opacification
      was applied during the surgery, and, in the postoperative period, eye drops and
      two subconjunctival injections of corticosteroids were applied. Accommodation was
      stimulated with carbachol iontophoresis or pilocarpine and was measured with a
      Hartinger refractometer at regular times during a follow-up period of 37 weeks in
      five monkeys. In one monkey, lens thickness changes were measured with A-scan
      ultrasound. RESULTS: In group A, refraction measurement was possible in one
      monkey. In the three other animals in group A, postoperative inflammation and
      capsular opacification prevented refraction measurements. In group B, the maximum
      accommodative amplitude of the surgically treated eyes was 6.3 D. In three
      monkeys the accommodative amplitude decreased to almost 0 D after 37 weeks. In
      the two other monkeys, the accommodative amplitude remained stable at +/-4 D
      during the follow-up period. In group B, capsular opacification developed in the
      postoperative period, but refraction measurements could still be performed during
      the whole follow-up period of 37 weeks. CONCLUSIONS: A certain level of
      accommodation can be restored after lens refilling in adolescent rhesus monkeys.
      During the follow-up period refraction measurements were possible in all five
      monkeys that underwent the treatment designed to prevent inflammation and
      capsular opacification.

PMID- 16799043
TI  - An in vitro study of human lens epithelial cell adhesion to intraocular lenses
      with and without a fibronectin coating.
AB  - PURPOSE: To demonstrate differences in human lens epithelial cell adhesion to
      different intraocular lens biomaterials in vitro and to determine whether these
      differences can be influenced by coating the intraocular lens surface with
      commercially available fibronectin. METHODS: A prospective laboratory-based study
      comparing human lens epithelial cell adhesion to silicone (n=18),
      polymethylmethacrylate (PMMA; n=18), and acrylic (n=18) intraocular lenses in
      vitro. The three types of intraocular lenses were then coated with fibronectin:
      silicone (n=6), PMMA (n=6), and acrylic (n=6). The main outcome measure was the
      mean number of lens epithelial cells attached to each lens type after 24 hours of
      incubation. RESULTS: In the uncoated lens group, there was a significantly higher
      number of lens epithelial cells attached to the acrylic than to the silicone or
      PMMA lenses (P<0.001). Coating the lenses with fibronectin caused a significant
      increase in attachment of lens epithelial cells for all three lens types.
      CONCLUSIONS: There was a significant difference in the degree of lens epithelial
      cell attachment to the various types of intraocular lenses in vitro. Cell
      attachment was more prominent in the acrylic lenses, but the fibronectin coating
      negated differences in lens type and caused a significant increase in cell
      attachment across all groups.

PMID- 16799044
TI  - MALDI tissue imaging of ocular lens alpha-crystallin.
AB  - PURPOSE: To apply MALDI (matrix-assisted laser desorption ionization) tissue
      imaging methods to obtaining a profile of the distribution of the lens alpha
      crystallins and their modified forms in calf and mature bovine lenses. METHODS:
      Frozen bovine lenses were cut equatorially at -12 degrees C to -20 degrees C into
      10- to 40-microm sections depending on lens age. Tissue sections were mounted
      onto MALDI sample plates by ethanol soft-landing to maintain tissue integrity. A
      two-layered matrix deposition method was used to improve mass spectral
      reproducibility across sections. Molecular images of the two subunits of alpha
      crystallin and their modifications over approximately one-half of a single tissue
      section were reconstituted from mass spectral data sets acquired in 250-microm
      steps. Identification of protein truncation products and confirmation of
      phosphorylation distribution patterns were performed by reverse-phase liquid
      chromatography of soluble extracts from specific tissue regions followed by
      tandem mass spectrometry (LC/MS/MS). RESULTS: Distinct distribution patterns were
      observed for the two subunits of alpha-crystallin and their modified forms.
      alphaA-crystallin showed extensive truncation across whole sections, especially
      in the nuclei, whereas alphaB-crystallin was observed to be relatively stable.
      Both alphaA-crystallin and alphaB-crystallin displayed the highest level of
      phosphorylation in the middle cortex region, a finding confirmed by LC/MS/MS
      analysis of dissected regions. CONCLUSIONS: A new imaging technique has been
      successfully applied to molecularly characterize the spatial distribution of lens
      proteins and their modifications in lens sections. The different distributions of
      alpha-crystallin revealed in this study provide new leads in the investigation of
      underlying physiological significance of the modified forms of the two alpha
      crystallin subunits.

PMID- 16799045
TI  - A hierarchy of proliferative cells exists in mouse lens epithelium: implications
      for lens maintenance.
AB  - PURPOSE: To determine the distribution of slow-cycling cells, which are detected
      as label-retaining cells (LRCs), in mouse lens epithelium during postnatal
      development. METHODS: Pregnant BALB/c mice were injected intraperitoneally (twice
      daily) with tritiated thymidine (3H-TdR), beginning at 17 days of gestation until
      birth. At birth, the in utero-labeled neonatal mice were injected subcutaneously
      with 3H-TdR (twice daily) for 3 days. Mice were killed weekly for the first month
      and then at 3-week intervals up to 18.5 weeks (chase periods). Eyes were removed
      and processed for autoradiography. In living mice, small scrape wounds were made
      on the anterior surface of the lens of mice that had been "chased" for 18.5
      weeks. Twenty-four hours later, wounded mice received a single injection of BrdU.
      RESULTS: Immediately after the in utero/postnatal labeling period, 100% of the
      lens epithelial cells incorporated 3H-TdR, and all were heavily labeled. With
      time, the number of LRCs declined so that only 13% of the lens epithelial cells
      were labeled at 18.5 weeks. At this time the heaviest labeled cells were
      exclusively found in the central zone and represented 2% to 3% of the total LRCs.
      In contrast, lightly labeled cells were found in both the central and germinative
      zones. After wounding, the heavily labeled LRCs incorporated BrdU, indicating
      that these cells were healthy and could be recruited to proliferate. CONCLUSIONS:
      The heavily labeled LRCs, located exclusively in the central region, represent
      cells that divide very infrequently during homeostasis (putative stem cells); on
      perturbation, these cells can proliferate. The lightly labeled LRCs, located in
      the central and germinative zones, cycle more frequently than the heavily labeled
      ones. These LRCs may be phenotypically indistinguishable from stem cells and
      maintain the normal proliferative needs of the lens. A third population of
      actively cycling cells exists primarily in the germinative zone and represents
      the transit amplifying cells, which have a limited proliferative potential.

PMID- 16799046
TI  - Arginine 54 and Tyrosine 118 residues of {alpha}A-crystallin are crucial for lens
      formation and transparency.
AB  - PURPOSE: To identify new mouse models for studying roles of alphaAlpha-crystallin
      in vivo and to investigate why and how different mutations of the alphaAlpha
      crystallin gene lead to dominant or recessive cataracts. METHODS: Using mouse
      genetic approaches and slit lamp screening, we identified two mouse cataractous
      mutant lines. Causative genes were mapped by a genome-wide linkage analysis. DNA
      sequencing verified missense mutations of alphaA-crystallin gene in both mutant
      lines. Histology, imaging of green fluorescent protein (GFP)-positive lenses, and
      protein 2-DE gel were used to determine the morphologic and biochemical
      properties of mutant lenses. RESULTS: Two new alphaA-crystallin gene mutations
      were identified, alphaA-R54C (alphaA-Cys) and alphaA-Y118D, which cause recessive
      whole cataracts and dominant nuclear cataracts, respectively. In homozygous
      alphaA-Cys mutant mice, lens epithelial and fiber cells lost their characteristic
      cellular features and developed disrupted subcellular structures, such as actin
      filaments and mitochondria. The nuclear cataract caused by alphaA-Y118D mutation
      was associated with increased water-insoluble crystallins (alpha, beta, and gamma
      classes). These results suggest that the Arg54 residue in the N-terminal region
      is crucial for alphaA-crystallin to perform its roles in lens epithelial and
      fiber cells during development, whereas the Y118D mutation in the central alpha
      crystallin domain impairs alphaA-crystallin's ability to maintain the solubility
      of crystallin proteins in the lens. CONCLUSIONS: This work demonstrates that
      different regions of alphaA-crystallin mediate distinct functions in vivo. These
      two mutant mouse lines provide useful animal models for further investigating the
      multiple roles of alphaA-crystallin in the lens.

PMID- 16799047
TI  - Measurement and prediction of lateral diffusion within human sclera.
AB  - PURPOSE: Drug delivery via the sclera is a promising approach to retinal disorder
      treatments that require access to the posterior segment of the eye. To complement
      existing studies of transverse diffusion across the sclera, this study examined
      lateral diffusion within the sclera parallel to the scleral surface. METHODS:
      Using sulforhodamine as a model hydrophilic drug, rates of diffusion were
      measured in strips of human cadaveric sclera for up to 1 week. Data were analyzed
      with a mathematical model based on theoretical expressions for one-dimensional
      diffusion. RESULTS: Measurable amounts of sulforhodamine were detected at
      distances of 5 and 10 mm from the sulforhodamine donor reservoir at 4 hours and 3
      days, respectively. The effective lateral diffusivity of sulforhodamine was
      determined to be 3.82 x 10(-6) cm2/s, which is similar in magnitude to the
      transverse diffusivity. The theoretical model agreed with experimental values
      with an average error of 39%. CONCLUSIONS: This study shows that the lateral
      diffusion of sulforhodamine in human sclera is slow and localizes to the site of
      administration.

PMID- 16799048
TI  - Docosahexaenoic acid promotes photoreceptor differentiation without altering Crx
      expression.
AB  - PURPOSE: The precise molecular cues required for photoreceptor development are
      still unknown. Pax6 and Crx are essential during early retinal development and
      for photoreceptor differentiation, respectively. The lipid molecule
      docosahexaenoic acid (DHA) has also been shown to promote photoreceptor
      differentiation. Pax6 expression during the early steps in photoreceptor
      development and whether the mutual contribution of Crx and DHA enhances
      photoreceptor differentiation were investigated. METHODS: Neuroblast
      proliferation, Crx, and Pax6 expression were investigated in rat retinas in vivo
      and in neuronal cultures with or without DHA. BrdU incorporation, nestin and
      opsin expression, apical differentiation, and axonal outgrowth were determined by
      phase microscopy and immunochemistry. RESULTS: Pax6 expression occurred in all
      proliferating retinal neuroblasts in vivo; however, after their last mitotic
      division, photoreceptors stopped expressing Pax6 and started expressing Crx. In
      vitro, photoreceptor progenitors also showed a switch from Pax6 to Crx expression
      immediately after they exited the cell cycle and started differentiation. In
      contrast, those progenitors differentiating into amacrine neurons continued
      expressing Pax6 and did not express Crx. Most postmitotic photoreceptors
      expressing Crx showed little axon development and few of them expressed opsin.
      The addition of DHA dramatically increased differentiation in Crx-positive
      photoreceptors, enhancing opsin expression, apical differentiation, and axonal
      outgrowth, without affecting Crx expression. CONCLUSIONS: The results suggest
      that Pax6 and Crx expression are mutually exclusive during photoreceptor
      differentiation. Onset of Crx expression may provide a permissive stage that is
      essential to initiate photoreceptor differentiation, but additional support of
      DHA, among other environmental signals, is necessary to accomplish further
      differentiation.

PMID- 16799049
TI  - Visual field loss in young children and mentally handicapped adolescents
      receiving vigabatrin.
AB  - PURPOSE: In adult patients and in children of school age who have been treated
      with vigabatrin (VGB), persistent visual field defects have been reported as a
      side effect. To date, it is unknown to what extent VGB causes visual field loss
      in young children and mentally handicapped adolescents who cannot be tested with
      conventional perimetric METHODS: The purpose of the present study was to
      investigate VGB-induced visual field loss in these patients by using a
      noncommercial arc perimeter and a forced-choice, preferential-looking method. The
      visual field size was measured in 30 patients aged 1 to 15 years who had epilepsy
      and who were treated with VGB. The visual field of these patients was compared to
      the visual field of 70 control subjects. RESULTS: In eight (27%) patients who had
      been treated with VGB, the visual field was constricted compared with the visual
      field of the children belonging to the control group. CONCLUSIONS: Arc perimetry
      shows that mentally handicapped patients and children younger than 6 years
      treated with VGB have visual field loss compared with the loss reported in adult
      patients receiving VGB.

PMID- 16799050
TI  - Comparative effects of early postnatal ibuprofen and indomethacin on VEGF, IGF-I,
      and GH during rat ocular development.
AB  - PURPOSE: Ibuprofen and indomethacin are nonselective prostaglandin synthetase
      inhibitors that have been shown to improve oxygen-induced retinopathy in mice.
      Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I,
      and growth hormone (GH) are potent growth factors involved in retinal
      development. This study was conducted to examine and compare the effects of early
      postnatal ibuprofen and indomethacin on ocular and systemic VEGF, IGF-I, and GH
      during rat ocular development. METHODS: Newborn rats were treated with
      intraperitoneal injections of low and high doses of ibuprofen or indomethacin at
      birth (postnatal day [P]1) and on P2 and P3. A control group received equivalent
      volumes of saline. At P14, vitreous fluid, retinal homogenates, and serum were
      analyzed for VEGF, IGF-I, and GH protein levels. Retinal mRNA expression of VEGF
      splice variants (VEGF188, VEGF164, VEGF120), VEGF receptors (VEGFR-1, VEGFR-2,
      Npn-1, Npn-2), and pigment epithelium-derived factor (PEDF) were also examined.
      RESULTS: Animals treated with high-dose ibuprofen had significantly lower somatic
      growth and higher serum and vitreous IGF-I levels. High-dose ibuprofen decreased
      retinal VEGF levels and retinal VEGF164, VEGF120, and VEGFR-2 transcripts,
      resulting in a significant increase in the cecal period in 87% of rats at P14.
      Both indomethacin doses suppressed retinal VEGF164 transcripts without affecting
      VEGF receptors. CONCLUSIONS: Ibuprofen may be more effective than indomethacin
      for suppression of retinal VEGF signaling, suggesting a possible therapy for
      retinal neovascularization. However, deficits in somatic growth concurrent with
      higher systemic IGF-I levels suggests decreased IGF-I bioactivity. These adverse
      effects should be considered.

PMID- 16799051
TI  - Diabetic macular edema: correlation between microperimetry and optical coherence
      tomography findings.
AB  - PURPOSE: To compare the changes in macular sensitivity (microperimetry) and
      macular thickness with different degrees of diabetic macular edema. METHODS:
      Sixty-one eyes of 32 consecutive diabetic patients were included in this cross
      sectional study. All included eyes underwent functional and morphologic
      examination of the macular area. Best corrected visual acuity (ETDRS charts),
      macular sensitivity, and macular thickness were quantified. Lesion-related
      macular sensitivity and retinal fixation were investigated with an advanced,
      automatic microperimeter. Optical coherence tomography (OCT) was used to quantify
      macular thickness. RESULTS: The 61 included eyes were graded, by two retinal
      specialists, for diabetic macular edema as follows: 16 were graded as no macular
      edema (NE), 30 as non-clinically significant macular edema (NCSME), and 15 as
      clinically significant macular edema (CSME). Macular thickness significantly
      increased from the NE to the CSME group (P<0.0001), whereas macular sensitivity
      significantly decreased from the NE to the CSME group (P<0.0021). A significant
      correlation coefficient was noted between retinal sensitivity and normalized
      macular thickness (r=-0.37, P<0.0001). Linear regression analysis showed a
      decrease of 0.83 dB (P<0.0001) for every 10% of deviation of retinal thickness
      from normal values. Visual acuity and central macular sensitivity correlated
      significantly in the NCSME group (r=-0.6, P=0.0008), but not in the NE (r=-0.144,
      P=0.6) or in the CSME (r=-0.46, P=0.11) groups. CONCLUSIONS: Macular edema may be
      better documented by adding macular sensitivity mapping by microperimetry to
      macular thickness measurement by OCT and visual acuity determination because
      macular sensitivity seems to be a relevant explanatory variable of visual
      function, independent of macular thickness data. Moreover, microperimetry may be
      of value in predicting the outcome of diabetic macular edema, because it
      incorporates a functional measure that may supplement the predictive value of OCT
      and visual acuity.

PMID- 16799052
TI  - Prevalence of disease-causing mutations in families with autosomal dominant
      retinitis pigmentosa: a screen of known genes in 200 families.
AB  - PURPOSE: To survey families with clinical evidence of autosomal dominant
      retinitis pigmentosa (adRP) for mutations in genes known to cause adRP. METHODS:
      Two hundred adRP families, drawn from a cohort of more than 400 potential
      families, were selected by analysis of pedigrees. Minimum criteria for inclusion
      in the adRP cohort included either evidence of at least three generations of
      affected individuals or two generations with evidence of male-to-male
      transmission. Probands from each family were screened for mutations in 13 genes
      known to cause adRP: CA4, CRX, FSCN2, IMPDH1, NRL, PRPF3 (RP18), PRPF8 (RP13),
      PRPF31 (RP11), RDS, RHO, ROM1, RP1, and RP9. Families without mutations in
      autosomal genes and in which an X-linked mode of inheritance could not be
      excluded were tested for mutations in ORF 15 of X-linked RPGR. Potentially
      pathogenic variants were evaluated based on a variety of genetic and
      computational criteria, to confirm or exclude pathogenicity. RESULTS: A total of
      82 distinct, rare (nonpolymorphic) variants were detected among the genes tested.
      Of these, 57 are clearly pathogenic based on multiple criteria, 10 are probably
      pathogenic, and 15 are probably benign. In the cohort of 200 families, 94 (47%)
      have one of the clearly pathogenic variants and 10 (5%) have one of the probably
      pathogenic variants. One family (0.5%) has digenic RDS-ROM1 mutations. Two
      families (1%) have a pathogenic RPGR mutation, indicating that families with
      apparent autosomal transmission of RP may actually have X-linked genetic disease.
      Thus, 107 families (53.5%) have mutations in known genes, leaving 93 whose
      underlying cause is still unknown. CONCLUSIONS: Together, the known adRP genes
      account for retinal disease in approximately half of the families in this survey,
      mostly Americans of European origin. Among the adRP genes, IMPDH1, PRPF8, PRPF31,
      RDS, RHO, and RP1 each accounts for more than 2% of the total; CRX, PRPF3, and
      RPGR each accounts for roughly 1%. Disease-causing mutations were not found in
      CA4, FSCN2, NRL, or RP9. Because some mutations are frequent and some regions are
      more likely to harbor mutations than others, more than two thirds of the detected
      mutations can be found by screening less than 10% of the total gene sequences.
      Among the remaining families, mutations may lie in regions of known genes that
      were not tested, mutations may not be detectable by PCR-based sequencing, or
      other loci may be involved.

PMID- 16799053
TI  - Damage Thresholds for Exposure to NIR and Blue Lasers in an In Vitro RPE Cell
      System.
AB  - PURPOSE: Until reliable nonanimal systems of analysis are available, animal
      models will be necessary for ocular laser hazard analysis and for evaluating
      clinical applications. The purpose of this work was to demonstrate the utility of
      an in vitro system for laser bioeffects by identifying photothermal and
      photochemical cytotoxicity thresholds for continuous-wave (cw) and mode-locked
      (ml) laser exposures. METHODS: Exogenous melanosomes were added to hTERT-RPE1
      cells in exposure wells 1 day before laser exposure. Thermal or photochemical
      laser exposures were delivered to artificially pigmented retinal pigment
      epithelial (RPE) cultures, with subsequent assay for viability 1 hour after
      exposure. Beam delivery for the 1-hour photochemical exposures was via a modified
      culture incubator. The cytoprotective effect of pretreatment with two
      antioxidants was investigated. RESULTS: Phagocytosis of melanosomes by the RPE
      cells was efficient, yielding cultures of uniform pigmentation. The damage
      threshold for the thermal exposure was consistent with published in vivo results.
      Thresholds for both blue exposures (cw and ml) were identical. Overnight
      treatment of cells with ascorbic acid (AA) minimized cell death from both cw and
      ml blue laser exposure, whereas similar treatment with N-acetyl-L-cysteine (NAC)
      was less effective. CONCLUSIONS: The in vitro system described is suitable for
      measuring meaningful thermal and photochemical laser damage thresholds. The
      system is also useful in comparative laser bioeffects studies, such as
      comparisons between cw and ml laser exposures, cells with various degrees of
      pigmentation, and studies determining the efficacy and mechanisms of treatments
      altering the response of cells to lasers.

PMID- 16799054
TI  - Ames Waltzer deaf mice have reduced electroretinogram amplitudes and complex
      alternative splicing of Pcdh15 transcripts.
AB  - PURPOSE: Mutations of PCDH15, the gene encoding protocadherin 15, cause either
      nonsyndromic deafness DFNB23 or Usher syndrome type 1F (USH1F) in humans and
      deafness with balance problems in Ames waltzer (av) mice. Persons with USH1
      usually begin to exhibit signs of retinitis pigmentosa (RP) in early adolescence,
      but av mice are reported to have functional retinas. In this study, the auditory,
      visual and molecular biological phenotype of Pcdh15av-5J and Pcdh15av-Jfb mice is
      characterized, and their usefulness as animal models of USH1 is evaluated.
      METHODS: Hearing thresholds of mice between 6 and 10 weeks of age were measured
      by auditory brain stem response (ABR). Immunohistochemistry and histology were
      used to examine the effect of homozygosity of Pcdh15av-5J on stereocilia bundles
      of inner ear hair cells and on the photoreceptor cells of the retina. Scotopic
      and photopic Ganzfeld ERGs were recorded from homozygous Pcdh15av-5J and Pcdh15av
      Jfb mice at different ages. Heterozygous littermates served as control subjects.
      Measurements of the width of the outer nuclear layer (ONL) and the length of rod
      photoreceptor outer segment (ROS) were made. RESULTS: Homozygous Pcdh15av-5J mice
      have profound hearing loss and disorganized stereocilia bundles of inner ear hair
      cells. Compared with heterozygous littermates, homozygous Pcdh15av-5J and
      Pcdh15av-Jfb mutant mice had scotopic ERG amplitudes consistently reduced by
      approximately 40% at all light intensities. The b-to-a-wave ratio confirmed that
      the a- and b-waves were reduced proportionally in homozygous mutant mice.
      Histologic measurements of retinal sections revealed no significant differences
      in either the ONL width or the ROS length as a function of genotype. The
      protocadherin 15 labeling pattern with antisera PB303 in the retina of both
      heterozygous and homozygous Pcdh15av-5J mice was indistinguishable from the wild
      type. Wild-type Pcdh15 have many alternatively spliced isoforms. A novel isoform
      was found in the retina of homozygous Pcdh15av-5J mice, which appears to
      circumvent the effect of the mutant allele (IVS14-2A-->G), which causes skipping
      of exon 14, a shift in the translation reading frame and a premature stop codon
      in exon 15. CONCLUSIONS: Pcdh15(av-5J) and Pcdh15(av-Jfb) mice do not faithfully
      mimic the RP found in USH1 due to mutations of PCDH15, but have significantly
      attenuated ERG function in the absence of histologic change. The decline in ERG
      amplitude with a preserved b-to-a-wave ratio suggests a role for Pcdh15 in
      retinal function and/or generation of the ERG potentials. Understanding the
      molecular mechanism by which av mice circumvent degeneration of the retina might
      offer insights into potential therapies for USH1.

PMID- 16799055
TI  - Maculopathy due to the R345W substitution in fibulin-3: distinct clinical
      features, disease variability, and extent of retinal dysfunction.
AB  - PURPOSE: To determine (1) clinical features that distinguish maculopathy due to
      the R345W substitution in fibulin-3 from other forms of inherited or early-onset
      drusen, (2) the phenotypic variability, and (3) the extent of retinal disease in
      those with a positive molecular diagnosis. METHODS: Affected individuals
      underwent ophthalmic examination, digital color fundus photography, fundus
      autofluorescence (AF) imaging, and psychophysical testing with automated photopic
      and dark-adapted perimetry and fine matrix mapping. Blood samples were taken for
      DNA extraction and screening for the R345W mutation in fibulin-3. Patients were
      subsequently divided into mutation-positive and -negative groups, to compare the
      identified phenotypic findings in these two sets of subjects. RESULTS: Twenty
      nine subjects from 19 families were ascertained with inherited or early-onset
      drusen. Twenty-four (83%) subjects from 15 families were found to harbor the
      R345W fibulin-3 mutation. Peripapillary deposition and a radial distribution of
      macular drusen were consistent, distinguishing signs in the mutation-positive
      group. Subretinal neovascular membrane (SRNVM) was a rare occurrence, affecting
      only 1 of 48 eyes, whereas hyperpigmentation and atrophy of the retinal pigment
      epithelium (RPE) were common in older mutation-positive patients. Increased AF
      corresponding to the drusen was detected in both the mutation-positive and 
      negative groups. The phenotype in the group of patients positive for the R345W
      mutation was extremely variable, with evidence of interocular, intrafamilial, and
      interfamilial variability in visual loss, natural history, ophthalmoscopic
      findings, autofluorescence imaging, and psychophysical data. The novel finding of
      nonpenetrance was observed in a 62-year-old asymptomatic, mutation-positive man.
      The findings from detailed perimetry performed on a subset of subjects were
      consistent with the presence of widespread retinal dysfunction not isolated to
      the macula. CONCLUSIONS: Marked inter- and intrafamilial variation associated
      with the fibulin-3 R345W mutation in terms of retinal appearance, severity,
      progression, and nonpenetrance were identified. It was noted that SRNVM is a rare
      occurrence in R345W fibulin-3 maculopathy. These findings are helpful for advice
      regarding prognosis and for genetic counseling. The findings established that the
      presence of peripapillary deposit is highly likely to indicate that a patient
      carries the R345W mutation.

PMID- 16799056
TI  - Fundus near infrared fluorescence correlates with fundus near infrared
      reflectance.
AB  - PURPOSE: To analyze the occurrence of near infrared (NIR) fluorescence in
      relation to NIR reflectance, blue-light-excited autofluorescence, angiograms, and
      funduscopy. METHODS: Observational consecutive case series in patients with
      macular diseases. Imaging was performed with a confocal scanning laser
      ophthalmoscope for NIR reflectance, blue-light-excited autofluorescence, NIR
      fluorescence, and fluorescein and indocyanine green (ICG) angiograms. In cases in
      which NIR fluorescence was observed, five to nine images were averaged. The
      leakage of the scanning laser ophthalmoscope was analyzed. RESULTS: In the 291
      eyes analyzed, NIR fluorescence was observed in 51 and was graded weak in 27 with
      wet age-related macular degeneration (AMD, 10 cases), dry AMD with pigment
      clumping (n=7), chronic central serous choroidopathy (CSC; n=5), choroidal nevi
      (n=2), subretinal hemorrhages (n=2), and chloroquine maculopathy (n=1). Strong
      NIR fluorescence was found in 24 eyes, with wet AMD (n=14), subretinal
      hemorrhages (n=8), and choroidal nevi (n=2). Except for four eyes, we observed a
      strong correlation of NIR fluorescence and increased NIR reflectance at identical
      fundus location (92.2%). NIR fluorescence corresponded with increased blue-light
      excited autofluorescence in 21 of 31 patients with AMD and in 4 of 5 patients
      with chronic CSC, but in none of the 4 patients with nevi. Funduscopy showed that
      structures with NIR fluorescence were pigmented or consisted of degraded blood.
      Barrier filter leakage of the imaging system was 6.2x10(-6). CONCLUSIONS: The
      high correlation of NIR fluorescence and reflectance indicated that part of the
      observed NIR fluorescence is pseudofluorescence, whereas gray-scale analysis
      indicated that both NIR autofluorescence and pseudofluorescence contribute to the
      NIR fluorescence images. Quantification of leakage of the imaging system
      indicated a significant part of the observed NIR fluorescence is NIR
      autofluorescence. As NIR fluorescence derives from pigmented lesions, melanin is
      a possible source if NIR reflectance is also increased. Comparison with blue
      light-excited autofluorescence showed differences between AMD and patients with
      nevi. NIR autofluorescence was also detected in single cases of maculopathy
      without corresponding NIR reflectance.

PMID- 16799058
TI  - Apolipoprotein localization in isolated drusen and retinal apolipoprotein gene
      expression.
AB  - PURPOSE: To evaluate apolipoprotein (Apo) gene expression in native human retinal
      pigment epithelium (RPE) and neurosensory retina and to detect apolipoproteins
      within age-related, extramacular drusen. METHOD: Drusen were isolated manually
      from 10 eyes of 10 donors (age range, 58-93 years) with grossly normal maculas
      that were preserved in 4% paraformaldehyde within 6 hours of death. In
      cryosections of druse-enriched pellets (6-57 drusen per eye), the Apos A-I, A-II,
      B, C-I, C-II, C-III, E, and J were detected by indirect immunofluorescence. Two
      graders assessed the prevalence and pattern of immunoreactivity. mRNA transcripts
      were detected by reverse-transcription polymerase chain reaction (RT-PCR), with
      human hepatoma HepG2 cells as the positive control. RESULTS: Extramacular drusen
      were classified in two groups on gross appearance: transparent with a reflective
      shell and cloudy. The proportion of the latter increased significantly with age.
      All Apos examined were detectable, in descending order of prevalence: ApoE
      (99.5%), J (99.5%), C-I (93.1%), B (80.4%), A-I (61.0%), A-II (59.2%), C-II
      (57.7%), and C-III (16.6%). Immunoreactivity was either diffusely distributed
      throughout the drusen (56.7%), confined to the druse rim (16.0%), or both
      (21.2%). Six percent displayed evidence of organized substructure reminiscent of
      active remodeling. The proportion of diffusely labeled drusen decreased
      significantly with age for ApoE (P=0.034) and ApoE/C-I combined (P=0.027). RT-PCR
      products for Apos C-I, C-II, E, and J were found in retina and RPE; for ApoA-II
      in the retina only. The ApoC-III message was undetectable. CONCLUSIONS: To an
      emerging model of an RPE-secreted large lipoprotein particle implied by previous
      work, this study adds ApoC-I and ApoC-II, major modulators of lipoprotein lipase
      activity, and confirms previously demonstrated Apos A-I, B-100, and E. It is
      possible that a neutral lipid-rich druse shell containing Apos will be visible in
      the living fundus.

PMID- 16799057
TI  - Photoreceptor organization and rhythmic phagocytosis in the nile rat Arvicanthis
      ansorgei: a novel diurnal rodent model for the study of cone pathophysiology.
AB  - PURPOSE: To characterize rod and cone distribution, organization, and
      phagocytosis in the diurnal mouse-like rodent Arvicanthis ansorgei. METHODS:
      Retinas of adult A. ansorgei were processed for histology, electron microscopy
      and immunohistochemistry using rod- and mouse cone-specific antibodies. For
      phagocytosis studies, retinas were sampled every 3 hours under a 12-hour light
      dark cycle and processed for double-label immunohistochemistry. The number of
      phagosomes in the retinal pigmented epithelium were quantified with a
      morphometric system. RESULTS: A. ansorgei retinas were composed of 33% cones and
      67% rods, approximately 10 times more cones than mice and rats. Cones were
      arranged in two cell layers at the scleral surface, distributed uniformly across
      the entire retina. Cone arrestin was distributed throughout the dark-adapted
      cones, from outer segments to synapses, whereas short- and mid-wavelength cone
      opsins were restricted to outer segments. Short-wavelength cone density was
      mapped in wholemounted retinas, in a significantly higher number in the central
      region. Rhodopsin immunopositive (rod) phagosomes showed a small peak late in the
      dark phase, then a large burst 1 to 2 hours after light onset, after decreasing
      to low baseline levels by 12 AM. Mid-wavelength cone opsin immunopositive (cone)
      phagosomes were 10 times less numerous than rods, and demonstrated a broad peak 1
      to 2 hours after light onset. CONCLUSIONS: The diurnal rodent A. ansorgei
      possesses a large number of cones, organized in a strict anatomic array. Rod and
      cone outer segment phagocytosis and shedding can be monitored simultaneously and
      show similar profiles but different amplitudes. This species may constitute a
      valuable novel animal model for investigating cone pathophysiology.

PMID- 16799059
TI  - Retinal localization and copper-dependent relocalization of the Wilson and Menkes
      disease proteins.
AB  - PURPOSE: Menkes and Wilson diseases are associated with retinal degeneration. The
      Menkes and Wilson genes are homologous copper transporters, but differences in
      their expression pattern lead to different disease manifestations. To determine
      whether the Wilson and Menkes genes may act locally in the retina, this study was
      undertaken to assess retinal Wilson and Menkes expression and localization.
      METHODS: RT/PCR was used to test for the presence of Wilson and Menkes mRNAs in
      mouse and human retinas and retinal pigment epithelial cell lines. The Menkes and
      Wilson proteins were immunolocalized in human and mouse retinas and in the ARPE
      19 cell line. RESULTS: The Menkes mRNA and protein were present in the RPE and
      neurosensory retina whereas the Wilson mRNA and protein were limited to the RPE.
      In the RPE, both proteins localized to the Golgi. Increased copper concentration
      led to relocalization of the Wilson protein to a diffuse cytoplasmic
      distribution. CONCLUSIONS: Both the Menkes and Wilson proteins are present in the
      RPE. Since the RPE is a blood-brain barrier, these proteins most likely regulate
      not only their own copper levels but also copper levels of the overlying
      photoreceptors. Because the Wilson protein delivers copper to the ferroxidase
      ceruloplasmin in the liver, it is likely that the Wilson and/or Menkes proteins
      provide copper to ceruloplasmin made in the RPE. Retinopathy in Wilson and Menkes
      diseases may result not only from abnormal systemic copper levels but also from
      loss of retinal Wilson or Menkes protein.

PMID- 16799060
TI  - VEGF expression and receptor activation in the choroid during development and in
      the adult.
AB  - PURPOSE: Previous studies have demonstrated a role for the retinal pigment
      epithelium (RPE) in the development and maintenance of the choroidal vasculature,
      suggesting that RPE serves a trophic role for the choroidal vessels. The goal of
      this study was to determine the expression pattern of vascular endothelial growth
      factor (VEGF) and its receptors and their activation status in embryonic and
      adult choroid, with the purpose of providing cues regarding the role of VEGF in
      development and stabilization of the choroidal vasculature. METHODS: Transgenic
      VEGF-LacZ mice were used to examine VEGF expression in embryonic and adult eyes.
      Expression of VEGF isoforms and receptors in the RPE-choroid complex was assessed
      by RT-PCR and real-time PCR. VEGF receptor 2 expression was assessed by
      immunohistochemistry and its activation state was examined by immunoprecipitation
      followed by phosphotyrosine blot. RESULTS: VEGF is expressed by RPE throughout
      the choroidal vascular development and in the adult. The major VEGF isoforms
      detected in adult RPE were VEGF120 and VEGF164, with almost no detectable
      VEGF188. RT-PCR analysis showed expression of VEGF receptors and coreceptors in
      the RPE-choroid complex. VEGFR2 was detected in the choriocapillaris underlying
      the RPE. Immunoprecipitation and phosphotyrosine blot of this receptor revealed
      that VEGFR2 is activated in adult mouse and bovine choroids. CONCLUSIONS: The
      observations suggest that VEGF signaling is involved, not only in choroidal
      vessel formation, but perhaps also in the maintenance of the choriocapillaris.

PMID- 16799061
TI  - Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic
      rat and Ins2Akita-diabetic mouse retinas.
AB  - PURPOSE: To identify amacrine cells that are vulnerable to degeneration during
      the early stages of diabetes. METHODS: Whole retinas from streptozotocin (STZ)
      diabetic rats and Ins2(Akita) mice were fixed in paraformaldehyde. Apoptotic
      cells in the retina were quantified using terminal dUTP nick-end labeling (TUNEL)
      and active caspase-3 (CM-1) immunohistochemistry. Immunohistochemical markers for
      choline acetyltransferase (ChAT) and tyrosine hyroxylase (TH) were also used to
      quantify populations of amacrine cells in the Ins2Akita mouse retinas. RESULTS:
      The number of TUNEL-positive nuclei increased from 29+/-4 in controls to 72+/-9
      in the STZ-diabetic rat retinas after only 2 weeks of diabetes. In rats, CM-1
      immunoreactive (IR) cells were found primarily in the inner nuclear and ganglion
      cell layers after 2, 8, and 16 weeks of diabetes. At each end point, the number
      of CM-1-IR cells in the retina was elevated by diabetes. Approximately 2% to 6%
      of the CM-1-IR cells in the inner nuclear layer (INL) were double-labeled for TH
      immunoreactivity. After 6 months of diabetes in the Ins2Akita mouse, the
      morphology of the labeled ChAT-IR and TH-IR amacrine cell somas and dendrites
      appeared normal. A quantitative analysis revealed a 20% decrease in the number of
      cholinergic and a 16% decrease in dopaminergic amacrine cells in the diabetic
      mouse retinas, compared with the nondiabetic control. CONCLUSIONS: Dopaminergic
      and cholinergic amacrine cells are lost during the early stages of retinal
      neuropathy in diabetes. Loss of these neurons may play a critical role in the
      development of visual deficits in diabetes.

PMID- 16799062
TI  - The dipeptide Arg-Gln inhibits retinal neovascularization in the mouse model of
      oxygen-induced retinopathy.
AB  - PURPOSE: Premature infants undergoing intensive care are highly vulnerable to
      amino acid deprivation. Supplementation of glutamine or arginine has resulted in
      beneficial effects in human neonates. This study was conducted to examine the
      effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell
      growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE)
      cell cultures and on inhibition of neovascularization in the oxygen-induced
      retinopathy (OIR) model. METHODS: The effects of Arg-Gln on VEGF levels were
      measured in supernates from hRPE cells by using ELISAs. For in vivo studies,
      mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control
      dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were
      prepared and retinal vessel morphology examined. The contralateral eyes were
      embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was
      isolated from retinas of selected animals and was used to quantify VEGF mRNA by
      real-time RT-PCR. RESULTS: Treatment of hRPE cells with Arg-Gln decreased VEGF
      levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day
      reduced preretinal neovascularization by 82%+/-7% (P<0.005), when compared with
      the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64%+/-9% (P<0.001).
      CONCLUSIONS: Arg-Gln dramatically inhibited retinal neovascularization in the OIR
      model. This effect was associated with a reduction in retinal VEGF mRNA levels.
      Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely
      to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and,
      with future studies in human infants, may prove beneficial in the prevention of
      ROP.

PMID- 16799063
TI  - Protective effect of crocin against blue light- and white light-mediated
      photoreceptor cell death in bovine and primate retinal primary cell culture.
AB  - PURPOSE: The present study was performed to investigate the effect of crocin on
      blue light- and white light-induced rod and cone death in primary retinal cell
      cultures. METHODS: Primary retinal cell cultures were prepared from primate and
      bovine retinas. Fifteen-day-old cultures were exposed to blue actinic light or to
      white fluorescent light for 24 hours. Cultures were treated by the addition of
      different concentrations of crocin for 24 hours before light exposure or for 8
      hours after light exposure. Cultures kept in the dark were used as controls.
      Green nucleic acid stain assay was used to evaluate cell death. Rods and cones
      were immunolabeled with specific antibodies and counted. TUNEL labeling was used
      to detect fragmented DNA in fixed cells after light exposure. RESULTS: Primary
      retinal cell cultures contained a mixture of retinal cells enriched in
      photoreceptors, bipolar cells, and Muller cells. Twenty-four-hour exposure to
      blue and white light induced death in 70% to 80% of the photoreceptors in bovine
      and primate retinal cell cultures. Crocin protected the photoreceptors against
      blue light- or white light-mediated damage in a concentration-dependent manner
      with an EC50 of approximately 30 microM. TUNEL assays confirmed that crocin
      protected photoreceptors from light damage. CONCLUSIONS: These results show that
      blue and white light selectively induce rod and cone cell death in an in vitro
      model. Crocin protects retinal photoreceptors against light-induced cell death.

PMID- 16799064
TI  - Flavonoids protect human retinal pigment epithelial cells from oxidative-stress
      induced death.
AB  - PURPOSE: To determine whether specific dietary and synthetic flavonoids can
      protect human retinal pigment epithelial (RPE) cells from oxidative-stress
      induced death. METHODS: The efficacy and potency were determined of a variety of
      dietary and synthetic flavonoids on the survival of human ARPE-19 cells and
      primary human RPE cells treated with either hydrogen peroxide (H2O2) or t-butyl
      hydroperoxide (t-BOOH). We determined the effective concentrations (EC50s) and
      the toxicities (LD50s) of the flavonoids after 24 hours, by using the MTT assay.
      The efficacy of vitamins E and C on RPE cell survival were compared under
      identical conditions. The ability of specific flavonoids to protect RPE cells
      from cell death was determined at various time intervals after the cells were
      exposed to oxidative stress. The ability of flavonoids to block the accumulation
      of intracellular reactive oxygen species was examined with dichlorofluorescein
      (DCF) fluorescence. Finally, the ability of flavonoids to induce phase-2
      detoxifying enzymes was tested by immunoblot analysis for the transcription
      factor Nrf2 and the phase-2 gene product heme-oxygenase 1. RESULTS: Specific
      flavonoids protected human RPE cells from oxidative-stress-induced death with
      efficacies between 80% and 100% and potencies in the high-nanomolar and low
      micromolar range. The toxicities of most of the effective flavonoids were low.
      The effective flavonoids included the dietary flavonoids fisetin, luteolin,
      quercetin, eriodictyol, baicalein, galangin and EGCG, and the synthetic
      flavonoids, 3,6-dihydroxy flavonol and 3,7 dihydroxy flavonol. Several flavonoids
      can protect RPE cells even when they are added after the cells have been exposed
      to oxidative stress. The flavonoids acted through an intracellular route to block
      the accumulation of reactive oxygen species. Many of these flavonoids induced the
      expression of Nrf2 and the phase-2 gene product heme-oxygenase 1 in human RPE
      cells. CONCLUSIONS: The results identify a select group of flavonoids that
      protect RPE cells from oxidative-stress-induced death with a high degree of
      potency and low toxicity. Many of these flavonoids also induce the expression of
      phase-2 detoxification proteins which could function to provide additional
      protection against oxidative stress. This select group of flavonoids and the
      foods that contain high levels of these compounds may have some clinical benefit
      for patients with retinal diseases associated with oxidative stress.

PMID- 16799065
TI  - The beta-adrenergic receptor antagonist metipranolol blunts zinc-induced
      photoreceptor and RPE apoptosis.
AB  - PURPOSE: To determine the effect of zinc on retinal cells at concentrations at
      which it is known to cause oxidative stress. Furthermore, the effects of
      metipranolol, known to prevent retinal damage, and of other antiglaucoma drugs
      were determined on zinc-injured retinal cells. METHODS: Lipid peroxidation assays
      were conducted on rat brain and bovine retina-retinal pigment epithelial (RPE)
      membrane preparations. Immunohistochemistry, immunoblot analysis and the terminal
      deoxynucleotidyl transferase dUTP-linked nick-end labeling (TUNEL) procedure
      determined the effects of zinc with or without trolox or metipranolol on
      photoreceptor death in situ. The effect of treatments on cultured RPE cells was
      analyzed using cell viability assays, immunoblot analysis, and the TUNEL
      procedure. RESULTS: Zinc-induced lipid peroxidation of rat brain and bovine
      retina-RPE membranes, although the effect of the latter was of a (twofold)
      greater magnitude. Both effects, however, were similarly attenuated by
      metipranolol, desacetylmetipranolol, and trolox. Antiglaucoma drugs other than
      metipranolol had no effect. Intraocular injection of 150 microM zinc and
      treatment of cultured RPE cells with zinc led to mainly photoreceptor apoptosis
      and apoptotic death of RPE cells (50% death at 18 microM rising to 10% at 50
      microM), respectively. Zinc-induced apoptosis of cultured RPE cells and
      photoreceptors were attenuated only by metipranolol and trolox. CONCLUSIONS: The
      combined data suggest that oxidative injury to RPE cells and photoreceptors may
      be caused by elevated levels of zinc in diseases such as age-related macular
      degeneration (AMD) and that metipranolol may act as an efficacious antioxidant to
      blunt this process.

PMID- 16799066
TI  - Rod photoreceptor dysfunction in diabetes: activation, deactivation, and dark
      adaptation.
AB  - PURPOSE: To examine photoreceptor function in diabetes in detail by evaluating
      photoreceptor light activation, deactivation of the photoresponse, and recovery
      of the photoreceptor after bleaching (dark adaptation) in rats made diabetic with
      streptozotocin (STZ). METHODS: Animals were assigned to treated and control
      groups. Light activation in rod photoreceptors was established using a paired
      flash electroretinogram (ERG) protocol, and the leading edge of the a-wave was
      modeled with the mechanisms mediating phototransduction. Deactivation of the
      photoreceptor response was evaluated at three luminous exposures (1.4-2.2 log
      cd.m/s-2) using a variable interstimulus interval (ISI) paradigm. Dark adaptation
      was evaluated at 90-second intervals for 30 minutes after approximately 20%
      pigment bleach. At each time point, a paired-flash signal (1.4 log cd.s/m-2) was
      used to extract rod responses. RESULTS: Diabetic animals showed decreased
      amplitudes of the photoreceptor response 12 weeks after diabetes induction. No
      difference was found in the rate of deactivation of the photoresponse in diabetic
      rats. Normalized amplitudes showed that diabetic animals had significantly faster
      dark adaptation (P<0.01) than did controls. CONCLUSIONS: Although photoreceptor
      activation was abnormal, deactivation was unaltered after 12 weeks of diabetes.
      The faster relative recovery found in diabetes after bleach, in the presence of
      normal pigment dynamics, may reflect a decrease in outer segment lengths.

PMID- 16799067
TI  - Assessment of cortical visual field representations with multifocal VEPs in
      control subjects, patients with albinism, and female carriers of ocular albinism.
AB  - PURPOSE: In human albinism, part of the temporal retina projects abnormally to
      the contralateral hemisphere. This study was undertaken to test whether this
      abnormality can be identified with multifocal visual evoked potentials (mfVEPs)
      and whether it is evident in carriers of ocular albinism (OA1). METHODS: In 12
      control subjects, 11 patients with albinism, and 5 female carriers of OA1
      monocular pattern-reversal mfVEPs were recorded for 60 locations comprising a
      visual field of 44 degrees diameter (VERIS ver. 4.8; EDI, San Mateo, CA). For
      each eye and each stimulus location interhemispheric difference potentials were
      calculated and correlated with each other to assess the lateralization of the
      responses: positive and negative correlations indicate lateralization on same or
      opposite hemispheres, respectively. Misrouted optic nerves are expected to yield
      negative interocular correlations. Visual field locations without recordable
      responses were excluded from the analysis using a signal-to-noise threshold. The
      analysis also allowed assessment of the sensitivity and specificity of the
      detection of projection abnormalities. RESULTS: Sizable mfVEPs were obtained in
      all control subjects, carriers, and the three patients with albinism who had
      negligible nystagmus and visual acuity>0.25. Ninety-seven percent and 99% of the
      visual field locations were identified as normal in control subjects and
      carriers, respectively. While this indicates a specificity of the procedure of
      97%, the sensitivity was estimated as 75%. Finally, in albinism, 55% percent of
      the responses were abnormally represented. CONCLUSIONS: In the absence of
      nystagmus mfVEPs are a powerful tool to identify, in a spatially resolved manner,
      abnormal visual field representations. No local representation abnormalities were
      evident in the female carriers of OA1.

PMID- 16799068
TI  - Light-induced retinopathy: comparing adult and juvenile rats.
AB  - PURPOSE: To investigate the effect of chronic exposure to a bright, luminous
      environment, starting at the opening of the eyes, on the retinal structure and
      function of the suckling rat. METHODS: Juvenile Sprague-Dawley rats were exposed
      to 10,000 lux, for varying lengths of time between postnatal day (P)14 and P34.
      Results were compared with those obtained from adult rats exposed to the same
      light intensity and for the same duration. Electroretinograms (ERGs) were
      recorded at 1 month and 2 months of age, after which the retinas were harvested
      for histologic analysis. RESULTS: In juvenile rats, the severity of light-induced
      retinopathy (LIR) depended not only on the duration of the exposure but, more
      important, on the age of the rat at the onset of exposure. For example, in adult
      rats, 6-day exposure reduced the thickness of the outer nuclear layer (ONL) to
      less than 18% of normal, whereas in juvenile rats, 6-day exposure between P14 and
      P20 reduced it to 50% compared with 27% after exposure between P28 and P34. An
      adultlike effect could only be evidenced in rats exposed at the end of the first
      postnatal month (P28-P34). A similar age-dependent effect was also noted on the
      electroretinogram. CONCLUSIONS: These results show that, compared with the mature
      retina, the developing retina appears to be relatively preserved from the
      devastating consequences of exposure to bright light. This window of resistance
      to light damage gradually weakens as the juvenile rat approaches its 1-month
      anniversary.

PMID- 16799069
TI  - Vernier acuity is normal in migraine, whereas global form and global motion
      perception are not.
AB  - PURPOSE: A recent study has demonstrated that some people with migraine display
      impairments of intermediate stages of motion and form processing. Deficits were
      identified by using tasks that required that local stimulus attributes be
      integrated into global percepts. Neurons capable of global processing of form and
      motion are known to be present in extrastriate cortical areas V4 and V5,
      respectively. It is not clear from the literature whether deficits of global
      processing in migraineurs are likely to arise from reduced input to extrastriate
      cortex from primary visual cortex (V1). The purpose of the study was to compare
      presumed measures of V1 performance (vernier acuity) to measures of global form
      and motion perception in migraineurs. METHODS: Thirty migraineurs (17 with aura,
      and 13 without) and 20 age-matched nonheadache control subjects participated.
      Intermediate level motion and form perceptions were measured using global dot
      motion stimuli and Glass patterns, respectively. Vernier stimuli were broad
      vertical bars composed of small dot elements. Both a static luminance stimulus
      and a motion defined form vernier stimulus were used. RESULTS: Mean migraine and
      control group performance were not significantly different for either vernier
      task (static: t(48)=0.39, P=0.70; motion: t(48)=0.29, P=0.77). Mean migraine
      group performance was significantly worse than in control subjects for both the
      global form (t(48)=2.06, P=0.04) and global motion (t(48)=2.87, P<0.01) tasks.
      CONCLUSIONS: On average, migraineurs demonstrate abnormalities of intermediate
      stages of both motion and form processing. These abnormalities do not appear to
      arise from dropout of performance at V1, as vernier acuity was normal in the same
      individuals.

PMID- 16799070
TI  - Sweep visual evoked potential grating acuity thresholds paradoxically improve in
      low-luminance conditions in children with cortical visual impairment.
AB  - PURPOSE: Children with cortical or cerebral visual impairment (CVI) often
      experience photophobia. In a study conducted to test whether this clinical
      phenomenon affects visual function, the sweep visual evoked potential (VEP) was
      used to evaluate cortical responses to grating stimuli in two luminance
      conditions: low and normal. METHODS: Twenty children (age range, 7 months to 4
      years 10 months) with CVI and 17 age-matched control subjects were examined.
      Testing conditions consisted of a swept grating stimulus shown against a normal
      background luminance (109 cd/m2) and against a low-luminance background (20
      cd/m2). Thresholds in these two luminance conditions were compared. Response
      amplitudes across the spatial frequency domain were also compared. RESULTS:
      Children with CVI paradoxically have improved grating acuity thresholds when the
      stimulus is shown using a low-luminance background (P=0.006). Response amplitudes
      are also increased in low luminance. In control children, luminance had no
      significant effect on response amplitudes or thresholds. CONCLUSIONS: Increased
      luminance causes a worsening of acuity thresholds in children with CVI. Response
      amplitudes are also diminished in normal luminance. This finding has implications
      for optimal viewing and learning conditions for children with CVI.

PMID- 16799071
TI  - Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle
      hypertrophy.
AB  - RATIONALE: Hypoxia-induced pulmonary hypertension involves hypoxia-inducible
      factor-1alpha (HIF-1alpha) activation as well as elevated resting calcium levels.
      Cyclosporin A (CsA) inhibits calcium-induced calcineurin activation and blocks
      the stabilization of HIF-1alpha in cultured cells. OBJECTIVES: We hypothesized
      that treatment of rats with CsA would prevent HIF-1-dependent gene transcription,
      lower specific responses to acute hypoxia, and prevent pulmonary hypertension and
      right ventricle hypertrophy resulting from prolonged exposure to hypoxia.
      METHODS: Acute and chronic responses to hypoxia were studied in rats treated or
      not treated with CsA (25 mg x kg(-1) x d(-1)). MEASUREMENTS: Transcript levels of
      genes encoding the serotonin transporter or four HIF-1 target genes, in rats
      exposed for 6 h to ambient hypoxia, treated or not by CsA, were measured. In vivo
      hemodynamics, hematocrit, and heart morphologic characteristics were assessed in
      rats subjected to hypoxia for 3 wk, treated or not treated with CsA. Changes in
      mRNA levels of the modulatory calcineurin-interacting protein-1 (MCIP-1) were
      used as a sensitive indicator of calcineurin activity in lung and heart. MAIN
      RESULTS: Acute exposure to hypoxia led to a marked increase in mRNA levels of
      serotonin transporter, modulatory calcineurin-interacting protein-1, and HIF-1
      target genes, which was blunted by CsA treatment. Prolonged exposure to hypoxia
      raised right ventricle pressure, induced right ventricle hypertrophy, and
      activated cardiac calcineurin, effects that were fully prevented by CsA
      treatment. CONCLUSIONS: These results suggest that CsA prevents hypoxia-induced
      pulmonary hypertension and right ventricle hypertrophy, either by inhibiting HIF
      1 transcriptional activity in lung, by decreasing calcineurin activity in lung
      and heart, by direct effects of CsA, or by a combination of these factors.

PMID- 16799072
TI  - Dynamic antigen-specific T-cell responses after point-source exposure to
      Mycobacterium tuberculosis.
AB  - RATIONALE: The kinetics of Mycobacterium tuberculosis-specific Th1-type T-cell
      responses after M. tuberculosis infection are likely to be important in
      determining clinical outcome. OBJECTIVE: To investigate the kinetics of T-cell
      responses, in the context of a point-source school tuberculosis outbreak, in
      three groups of contacts who differed by preventive treatment status and
      tuberculin skin test (TST) results: 38 treated TST-positive students, 11
      untreated TST-positive staff, and 14 untreated students with negative or
      borderline TST results. METHODS: We used the ex vivo IFN-gamma enzyme-linked
      immunospot assay (ELISpot) to track T cells specific for two region of difference
      1 (RD1) antigens, early secretory antigenic target 6 and culture filtrate protein
      10, for 18 mo after cessation of tuberculosis exposure. MAIN RESULTS: The treated
      TST-positive students had an average 68% decline in frequencies of RD1-specific
      IFN-gamma-secreting T cells per year (p < 0.0001) and 6 of 38 students had no
      detectable RD1-specific T cells by 18 mo. No change in frequencies of these cells
      was observed in the untreated TST-positive staff (p = 0.38) and none were ELISpot
      negative at 18 mo. Of the 14 untreated students, 7 were persistently ELISpot
      positive (all of whom had borderline TST results), and 7 became ELISpot-negative
      (all but one had negative TST results) during follow-up. CONCLUSIONS: The
      decrease in M. tuberculosis-specific T cells and their disappearance in a
      proportion of treated students likely reflect declining antigenic and bacterial
      load in vivo induced by antibiotic treatment. The observed disappearance of M.
      tuberculosis-specific T cells in the untreated TST-negative contacts suggests
      that an acute resolving infection may occur in some contacts.

PMID- 16799073
TI  - An update on the diagnosis of tuberculosis infection.
AB  - Targeted testing and treatment of individuals with latent tuberculosis infection
      at increased risk of progression to active disease is a key element of
      tuberculosis control. This strategy is limited by the poor specificity of the
      tuberculin skin test in populations vaccinated with bacille Calmette-Guerin and
      its low sensitivity in immunosuppressed persons, who are at highest risk of
      progression. Two blood tests (T-SPOT.TB and QuantiFERON-TB Gold), based on
      detection of IFN-gamma released by T cells in response to M. tuberculosis
      specific antigens, may offer an improvement on the skin test. However, validation
      is challenging due to the lack of a diagnostic gold standard. This critical
      appraisal of published evidence summarizes the diagnostic accuracy of the new
      tests. The blood tests have operational advantages over the skin test because no
      return visit is required, results are available by the next day, and repeated
      testing does not cause boosting. Both tests are significantly more specific than
      the skin test in populations vaccinated with bacille Calmette-Guerin. The data
      suggest that T-SPOT.TB may be more sensitive than the skin test. Data in groups
      at high risk of progression to disease are scarce, and more research is needed in
      these populations, but it is clear that T-SPOT.TB performs better than the skin
      test in young children and HIV-infected people with active tuberculosis.
      Incorporation of these tests into programs for targeted testing of latent
      tuberculosis infection will reduce false-positive and false-negative results
      inherent in tuberculin testing, equipping clinicians with more accurate tools for
      tuberculosis control and elimination in the 21st century.

PMID- 16799074
TI  - Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary
      disease.
AB  - IMPACT: This study explores the use of measuring plasma biomarkers at
      exacerbation of chronic obstructive pulmonary disease (COPD), providing insight
      into the underlying pathogenesis of these important events. RATIONALE: The use of
      measuring C-reactive protein (CRP) to confirm exacerbation, or to assess
      exacerbation severity, in COPD is unclear. Furthermore, it is not known whether
      there may be more useful systemic biomarkers. OBJECTIVE: To assess the use of
      plasma biomarkers in confirming exacerbation and predicting exacerbation
      severity. METHODS: We assessed 36 biomarkers in 90 paired baseline and
      exacerbation plasma samples from 90 patients with COPD. The diagnosis of
      exacerbation fulfilled both health care use and symptom-based criteria. Biomarker
      concentrations were related to clinical indices of exacerbation severity.
      Interrelationships between biomarkers were examined to gain information on
      mechanisms of systemic inflammation at exacerbation of COPD. MEASUREMENTS AND
      MAIN RESULTS: To confirm the diagnosis of exacerbation, the most selective
      biomarker was CRP. However, this was neither sufficiently sensitive nor specific
      alone (area under the receiver operating characteristic curve [AUC], 0.73; 95%
      confidence interval, 0.66-0.80). The combination of CRP with any one increased
      major exacerbation symptom recorded by the patient on that day (dyspnea, sputum
      volume, or sputum purulence) significantly increased the AUC to 0.88 (95%
      confidence interval, 0.82-0.93; p<0.0001). There were no significant
      relationships between biomarker concentrations and clinical indices of
      exacerbation severity. Interrelationships between biomarkers suggest that the
      acute-phase response is related, separately, to monocytic and lymphocytic
      neutrophilic pathways. CONCLUSIONS: Plasma CRP concentration, in the presence of
      a major exacerbation symptom, is useful in the confirmation of COPD exacerbation.
      Systemic biomarkers were not helpful in predicting exacerbation severity. The
      acute-phase response at exacerbation was most strongly related to indices of
      monocyte function.

PMID- 16799075
TI  - Impact of a lung transplantation donor-management protocol on lung donation and
      recipient outcomes.
AB  - RATIONALE: One of the limitations associated with lung transplantation is the
      lack of available organs. OBJECTIVE: To determine whether a lung donor-management
      protocol could increase the number of lungs for transplantation without affecting
      the survival rates of the recipients. METHODS: We implemented the San Antonio
      Lung Transplant protocol for managing potential lung donors according to
      modifications of standard criteria for donor selection and strategies for donor
      management. We then compared information gathered during a 4-yr period, during
      which the protocol was used with information gathered during a 4-yr period before
      protocol implementation. Primary outcome measures were the procurement rate of
      lungs and the 30-d and 1-yr survival rates of recipients. MAIN RESULTS: We
      reviewed data from 711 potential lung donors. The mean rate of lung procurement
      was significantly higher (p < 0.0001) during the protocol period (25.5%) than
      during the pre-protocol period (11.5%), with an estimated risk ratio of 2.2 in
      favor of the protocol period. More patients received transplants during the
      protocol period (n = 121) than during the pre-protocol period (n = 53; p <
      0.0001). Of 98 actual lung donors during the protocol period, 53 (54%) had
      initially been considered poor donors; these donors provided 64 (53%) of the 121
      lung transplants. The type of donor was not associated with significant
      differences in recipients' 30-d and 1-yr survival rates or any clinical measures
      of adequate graft function. CONCLUSIONS: The protocol was associated with a
      significant increase in the number of lung donors and transplant procedures
      without compromising pulmonary function, length of stay, or survival of the
      recipients.

PMID- 16799076
TI  - Small airway function improvement after smoking cessation in smokers without
      airway obstruction.
AB  - OBJECTIVE: Studying smokers with normal spirometry requires monitoring tools of
      the peripheral lung. A validated multiple breath washout technique was used to
      assess possible recovery of smoking-induced small airway malfunction in acinar
      and conductive lung zones. METHODS: Eighty-seven smokers with a smoking history
      of at least 10 pack-years but absence of spirometric airflow obstruction were
      invited for assessment of lung function and small airway function at baseline and
      after 1 wk, 3 mo, 6 mo, and 12 mo of smoking cessation. A control group of 16
      persistent smokers was studied at the same time intervals. MEASUREMENTS AND MAIN
      RESULTS: Of the 87 smokers, 66, 32, 28, and 21% successfully ceased smoking for 1
      wk, 3 mo, 6 mo, and 12 mo, respectively. Lung function parameters remained
      essentially unaffected by smoking cessation. Ventilation heterogeneity showed
      transient improvements after 1 wk in the acinar lung compartment with a return to
      baseline afterwards. By contrast, there were persistent improvements in the
      conductive airway compartment; for example, smokers who successfully quit smoking
      for 12 mo (n=18) showed a 30 and 42% reduction of conductive airways abnormality
      after 1 wk and 1 yr, respectively. CONCLUSIONS: Smokers with early signs of small
      airway malfunction who successfully quit smoking show sustained improvements of
      conductive airway malfunction. In contrast, acinar airway malfunction quickly
      returns to baseline after a transient improvement.

PMID- 16799077
TI  - Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast
      reticulum.
AB  - BACKGROUND: Usual interstitial pneumonia (UIP), the pathologic correlate of
      idiopathic pulmonary fibrosis, contains characteristic discrete areas of
      fibroblasts, myofibroblasts, and newly formed collagen, termed "fibroblast foci."
      These lesions are argued to represent isolated sites of recurrent acute lung
      injury and suggested to be the mechanism of disease progression. We hypothesized
      that, rather than isolated, these lesions are part of an organized neoplasm.
      METHODS: Morphometric analysis of pentachrome-stained histologic sections of UIP
      was performed. Using point-counting technique on serial sections, fibroblast
      foci, arteries, and macrophage clusters were identified and we determined their
      individual "connectiveness" by estimating the Euler number. Two-dimensional
      micrographs were collated into a three-dimensional array from which a visual
      three-dimensional reconstruction could be constructed. Clonality analysis was
      performed using human androgen receptor gene methylation assay. RESULTS: Blood
      vessels show significant connectivity with a Euler number of 2, whereas
      macrophage clusters exhibited no connectivity. The fibroblast foci showed a high
      level of interconnection with Euler numbers ranging from 19 to 39. The computer
      generated three-dimensional models provide a visual confirmation of this
      connectiveness. Human androgen receptor gene methylation assay analysis of the
      foci showed balanced methylation consistent with polyclonality. CONCLUSIONS: The
      fibroblast foci of UIP are the leading edge of a complex reticulum that is highly
      interconnected and extends from the pleura into the underlying parenchyma. It is
      a reactive, rather than a malignant, process.

PMID- 16799078
TI  - Neurokinin-1 receptor blockade and murine lung tumorigenesis.
AB  - RATIONALE: Analogous to the adenoma-carcinoma sequence in the colon, it has been
      proposed that adenocarcinoma (AC) in the lung arises from adenomatous hyperplasia
      that progresses through atypical adenomatous hyperplasia to AC. However, the data
      supporting this sequence are largely circumstantial and the almost impossible
      task of identifying these lesions before resection rules out any longitudinal
      study in humans. OBJECTIVES, METHODS, AND RESULTS: We show in mice that the loss
      of function of the neurokinin-1 receptor (NK-1R)-due to either a pharmacologic or
      genetic manipulation-results in a sequence of morphologic changes in response to
      bleomycin treatment that precede the development of AC. We also demonstrate that
      a series of alterations in gene expression of proliferation markers (i.e., PCNA
      and Ki-67) and cell cycle regulators (i.e., FHIT, p53, and p21) characterizes the
      sequence of the precursor lesions. The loss of function of the NK-1R results in
      changes of the apoptotic rate and in a delay of DNA break recovery of alveolar
      epithelial cells following bleomycin treatment. The NK-1R blockade interferes
      with a caspase-independent pathway of apoptosis by affecting both the
      translocation of Nur77 into the cytoplasm and the expression of some important
      Bcl2 family members such as Bcl2 and Bak. CONCLUSIONS: To our knowledge, this is
      the first model to demonstrate a role for NK-1R in lung epithelial cell death and
      tumorigenesis. This animal model may provide new information on the biology of AC
      and will facilitate designing and testing of new therapeutic interventions.

PMID- 16799079
TI  - Diagnostic percutaneous transthoracic needle biopsy does not affect survival in
      stage I lung cancer.
AB  - RATIONALE: Lung cancer dissemination has been cited as a potential adverse
      consequence of diagnostic percutaneous transthoracic needle biopsy (PTNB) of lung
      nodules. Despite multiple reports in the literature of malignant spread along the
      needle track, the potential effect of lung cancer dissemination after PTNB on
      survival is unknown. OBJECTIVE: To evaluate whether diagnostic PTNB is associated
      with increased risk of lung cancer death. METHODS: This study included 8,607
      cases of surgically resected stage I non-small cell lung cancer diagnosed between
      1991 and 1999 from the Surveillance, Epidemiology, and End Results (SEER)
      registry linked to Medicare records. Overall and lung cancer-specific survival of
      patients who had and did not have PTNB was compared using Kaplan-Meier curves.
      Stratified survival analyses and Cox regression were used to compare survival
      with adjustment for potential confounders. RESULTS: Approximately 36% of patients
      underwent diagnostic PTNB. Overall and lung cancer-specific survival did not
      differ in patients that underwent PTNB as part of their cancer diagnostic work-up
      and those who did not (p = 0.57 and 0.46, respectively). In stratified and
      multivariate analysis, PTNB was not associated with an increased risk of death
      after controlling for age, race, income, access to care, comorbidities, tumor
      histology and size, and type of treatment received. CONCLUSIONS: In this large
      national sample, preoperative PTNB was not associated with increased risk of
      death. These data suggest that PTNB can be safely used for the work-up of
      pulmonary nodules when there is a suspicion of lung cancer.

PMID- 16799080
TI  - The effect of biomass burning on respiratory symptoms and lung function in rural
      Mexican women.
AB  - BACKGROUND: The use of biomass as a cooking fuel is commonplace in developing
      countries and has been associated with chronic bronchitis and obstructive airway
      disease. METHODS: A cross-sectional survey was done in the village of Solis,
      close to Mexico City. Lifelong nonsmoking women 38 yr of age or older (n=841)
      completed a questionnaire on respiratory symptoms and illnesses and on cooking
      fuel use, and performed spirometry in their homes. Particulate matter
      concentration was measured with a nephelometer in the kitchen for 1 h, while the
      subject was cooking. RESULTS: The peak indoor concentration of particulate matter
      (PM10, particles with a diameter of 10 microm or less) often exceeded 2 mg/m3.
      Compared with those cooking with gas, current use of a stove burning biomass fuel
      was associated with increased reporting of phlegm (27 vs. 9%) and reduced
      FEV1/FVC (79.9 vs. 82.8%). Levels of FEV1 were 81 ml lower and cough was more
      common (odds ratio, 1.7; 95% confidence interval, 1.0-2.8) in women from homes
      with higher PM10 concentrations. All women found with moderate airflow
      obstruction (Global Initiative for Chronic Obstructive Lung Disease stage II and
      above) were cooking with biomass stoves. CONCLUSION: Women cooking with biomass
      fuels have increased respiratory symptoms and a slight average reduction in lung
      function compared with those cooking with gas.

PMID- 16799081
TI  - Matrix regulation of lung injury, inflammation, and repair: the role of innate
      immunity.
AB  - Mechanisms that regulate host defense after noninfectious tissue injury are
      incompletely understood. Our laboratory is interested in the role of the
      extracellular matrix glycosaminoglycan hyaluronan in the regulation of lung
      inflammation and fibrosis. We have identified key roles for two cell surface
      receptor systems that interact with hyaluronan to control lung inflammation and
      tissue repair. Hematopoietic CD44 is necessary to clear hyaluronan fragments that
      are produced after lung injury. Failure to clear hyaluronan fragments leads to
      unremitting inflammation. However, in the absence of CD44, alveolar macrophages
      continue to produce chemokines in response to hyaluronan fragments, implicating
      another receptor system in controlling macrophage effector function. We found
      that Toll-like receptors 2 and 4 (TLR2 and TLR4) are responsible for macrophage
      inflammatory gene expression in response to hyaluronan fragments. Although TLR2
      and TLR4 initiate the innate immune response in noninfectious inflammation, they
      have a protective role against lung injury on alveolar epithelial cells.

PMID- 16799082
TI  - Progress in chronic obstructive pulmonary disease genetics.
AB  - Familial aggregation of chronic obstructive pulmonary disease (COPD) has been
      demonstrated, suggesting that genetic factors likely influence the variable
      development of chronic airflow obstruction in response to smoking. A variety of
      approaches have been used to identify novel COPD susceptibility genes, including
      association studies, linkage analysis, and rare variant analysis. Future
      directions for COPD research include genomewide association studies and animal
      model genetic studies.

PMID- 16799083
TI  - Understanding our drugs and our diseases.
AB  - Analysis of mouse genetic models of human disease-associated traits has provided
      important insight into the pathogenesis of human disease. As one example,
      analysis of a murine genetic model of osteoporosis demonstrated that genetic
      variation within the 15-lipoxygenase (Alox15) gene affected peak bone mass, and
      that treatment with inhibitors of this enzyme improved bone mass and quality in
      rodent models. However, the method that has been used to analyze mouse genetic
      models is very time consuming, inefficient, and costly. To overcome these
      limitations, a computational method for analysis of mouse genetic models was
      developed that markedly accelerates the pace of genetic discovery. It was used to
      identify a genetic factor affecting the rate of metabolism of warfarin, an
      anticoagulant that is commonly used to treat clotting disorders. Computational
      analysis of a murine genetic model of narcotic drug withdrawal suggested a
      potential new approach for treatment of narcotic drug addiction. Thus, the
      results derived from computational mouse genetic analysis can suggest new
      treatment strategies, and can provide new information about currently available
      medicines.

PMID- 16799084
TI  - Transforming growth factor beta: a central modulator of pulmonary and airway
      inflammation and fibrosis.
AB  - The requirement for precise geometric organization of endothelial cells and
      epithelial cells makes the gas-exchange region of the lung especially vulnerable
      to the adverse consequences of toxic products released from inflammatory cells.
      However, as a filter for large volumes of atmospheric gas, the lung is
      continually exposed to microorganisms and other toxic insults that require robust
      inflammatory defense. Enhanced production of extracellular matrix proteins is one
      important mechanism for restricting tissue damage, but excessive matrix
      production also has serious adverse effects on gas exchange. The amazing ability
      of the lung to recover from a barrage of environmental insults depends on
      precisely regulating both inflammation and extracellular matrix production in
      space and time. Below I review some of the evidence implicating members of the
      transforming growth factor beta family as critical mediators of this delicate
      dance and describe examples of how disruption of this balance by alterations in
      the magnitude of spatially restricted transforming growth factor beta activation
      can contribute to pathologic consequences of alveolar and airway injury and
      inflammation.

PMID- 16799085
TI  - Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in
      fibrosis and alveolar remodeling.
AB  - Inflammation and tissue remodeling with pathologic fibrosis are common
      consequences of Th2 responses in the lung and other organs. Interleukin (IL)-13
      and transforming growth factor-beta1 (TGF-beta(1)) are frequently coexpressed in
      these responses and are believed to play important roles in the pathogenesis of
      Th2-induced pathologies. To shed light on the mechanisms of these responses,
      overexpression transgenic approaches were used to selectively target each of
      these cytokines to the murine lung. IL-13 proved to be a potent stimulator of
      eosinophilic inflammation, mucus metaplasia, tissue fibrosis, and alveolar
      remodeling. CC chemokines, specific chemokine receptors (CCR2, CCR1), adenosine
      metabolism, vascular endothelial growth factor, and IL-11 contributed to the
      genesis of these responses. IL-13 also induced tissue fibrosis, at least in part,
      via its ability to induce and activate TGF-beta(1). In the TGF-beta(1) transgenic
      mouse, epithelial apoptosis preceded the onset of tissue fibrosis and alveolar
      remodeling. In addition, chemical (Z-VAD-fmk) and genetic (null mutations of
      early growth response gene 1) interventions blocked apoptosis and ameliorated TGF
      beta(1)-induced fibrosis and alveolar restructuring. These studies define an IL
      13-TGF-beta(1) pathway of tissue remodeling that regulates inflammation, mucus
      metaplasia, apoptosis, vascular responses, and fibrosis in the lung. They also
      highlight the intimate relationship between apoptosis and fibrosis induced by TGF
      beta(1). By defining the complexities of this pathway, these studies highlight
      sites at which therapies can be directed to control these important responses.

PMID- 16799086
TI  - Neutrophil elastase: mediator of extracellular matrix destruction and
      accumulation.
AB  - Of the myriad proteolytic enzymes implicated in the development of lung disease,
      neutrophil elastase has undoubtedly some of the most versatile effects. Although
      its key physiologic role is in innate host defense, it can also participate in
      tissue remodeling and possesses secretagogue actions that are now recognized as
      important to local inflammatory responses. Although unopposed neutrophil elastase
      activity has been implicated in the development of emphysema for several decades,
      only relatively recently has a pathogenetic function been ascribed to this serine
      proteinase in situations where excessive extracellular matrix deposition occurs.
      The use of genetically manipulated animal models is starting to uncover the
      potential ways in which its actions might influence fibrotic lung repair.
      Emerging evidence suggests that the engagement of cellular pathways with more
      direct effects on fibrogenic mediator generation and collagen synthesis appears
      to underpin the actions of neutrophil elastase in promoting lung matrix
      accumulation.

PMID- 16799088
TI  - Remodeling in asthma and chronic obstructive pulmonary disease.
AB  - Airway and lung tissue remodeling and fibrosis play an important role in the
      development of symptoms associated with lung function loss in asthma and chronic
      obstructive pulmonary disease (COPD). In the past decades, much attention has
      been paid to the inflammatory cellular process involved in airway remodeling in
      these two diseases. However, it is increasingly clear that resident cells
      contribute to airway and lung tissue remodeling and to associated fibrosis as
      well. This article deals with some new aspects and discusses the role of
      vasculature and vascular endothelial growth factor in the development of airway
      obstruction and airway wall fibrosis in asthma and COPD. Moreover, it addresses
      the extracellular matrix (ECM) turnover as present in both asthma and COPD. All
      components of lung ECM (collagen, elastic fibers, proteoglycans) have been shown
      to be potentially altered in these two diseases. Finally, the interaction between
      transforming growth factor (TGF), Smad signaling, and TGF in the ECM turnover
      will be discussed. We propose that ECM damage and repair contribute to airway and
      lung tissue pathology and that the vasculature may enhance this process. The
      localization of this process is dependent on the etiology of the disease (i.e.,
      allergen-driven in asthma and smoke-driven in COPD) and the local environment in
      which the pathologic process takes place.

PMID- 16799089
TI  - The genetics of asthma: ADAM33 as an example of a susceptibility gene.
AB  - The ability to identify novel disease genes by positional cloning led to the
      identification of a disintegrin and metalloprotease (ADAM)33 gene on chromosome
      20p13 as a susceptibility gene for asthma. Case-control and family-based
      association studies have mostly confirmed a link between ADAM33 and asthma. Its
      restricted expression to mesenchymal cells as well as its association with
      bronchial hyperresponsiveness and accelerated decline in lung function over time
      point strongly to its involvement in the structural airway components of asthma,
      such as remodeling. Extensive alternative splicing, expression during branching
      morphogensis in the developing fetus, impaired lung function in childhood, the
      production of a soluble form linked to chronic asthma, and tight epigenetic
      regulation indicate a level of complexity in the way ADAM33 influences disease
      phenotype. Its recent association with chronic obstructive pulmonary disease as
      well as with asthma and lung development points to functions relating to airway
      wall modeling and remodeling as a general morphogenetic repair gene rather than
      being restricted to asthma.

PMID- 16799087
TI  - The stumbling block in lung repair of emphysema: elastic fiber assembly.
AB  - The mechanical properties of the lung are largely determined by the connective
      tissue networks laid down during development. The macromolecules most important
      for lung mechanics and structural integrity are collagen, elastin, and
      proteoglycans. Members of the fibrillar collagen gene family provide the
      structural framework of the various lung compartments and elastic fibers provide
      elastic recoil. Elastin is also an important architectural component that
      influences lung development, predominantly during the alveolar stage. Previous
      studies have conclusively shown that elastin degradation is a key step in the
      pathogenesis of chronic obstructive pulmonary disease. Exacerbating the disease
      process is the inability of lung cells to repair damaged elastic fibers, which
      leads to permanently compromised lung function and ongoing degenerative disease.
      Elastic fibers are among the most difficult matrix structures to repair because
      of their size, molecular complexity, and the requirement for numerous helper
      proteins to facilitate fiber assembly. Recent studies of elastin assembly
      combined with new insight into the functional role of elastic fiber proteins
      obtained from gene inactivation studies and linkage of human disease to elastin
      mutations provide new insight into the molecular and cellular complexities of
      elastin homeostasis.

PMID- 16799090
TI  - Mechanisms of airway obliteration after lung transplantation.
AB  - Post-transplant bronchiolitis obliterans, also called bronchiolitis obliterans
      syndrome, affects up to 50-60% of patients who survive 5 yr after surgery
      according to its clinical definition, which is based on the degree of obstructive
      airway disease. Alloimmune-independent and -dependent mechanisms produce injuries
      and inflammation of epithelial cells and subepithelial structures, leading to
      aberrant tissue repair. The triggering of innate immunity by various infections
      or chemical injuries after, for example, gastroesophageal reflux, may lead to the
      release of danger signals that are able to activate dendritic cells, a crucial
      link with adaptive immunity. Inflammation can also increase the expression and
      display of major histocompatibility alloantigens and thus favor the initiation of
      rejection episodes. These phenomena may be limited in time and location or may be
      protracted. Reducing the risk of alloimmune-independent factors may be as
      important as treating acute episodes of lung rejection. Excessive
      immunosuppression may be deleterious by increasing the risk of infection, thereby
      triggering innate and adaptive immunity. New potential therapeutic targets are
      emerging from the research performed on leukotriene receptors, chemokine
      receptors, and growth factors. Neutralizing these molecules reduces the initial
      mononuclear and polynuclear infiltrates or the subsequent fibroproliferative
      process and the neovascular changes, feeding this process.

PMID- 16799091
TI  - Using computed tomographic scanning to advance understanding of chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease is a syndrome that encompasses a variety of
      pathologies and underlying mechanisms. Progress in understanding mechanisms,
      testing therapies, and identifying contributing genetic factors will be
      facilitated by the availability of techniques to characterize patients with
      respect to the nature and extent of both parenchymal and airway diseases. This
      review discusses the applicability of computed tomographic scan analysis to this
      problem. The current state of the field is briefly reviewed and future directions
      for the field are proposed.

PMID- 16799092
TI  - Dynamic profiling of the post-translational modifications and interaction
      partners of epidermal growth factor receptor signaling after stimulation by
      epidermal growth factor using Extended Range Proteomic Analysis (ERPA).
AB  - In a recent report, we introduced Extended Range Proteomic Analysis (ERPA), an
      intermediate approach between top-down and bottom-up proteomics, for the
      comprehensive characterization at the trace level (fmol level) of large and
      complex proteins. In this study, we extended ERPA to determine quantitatively the
      temporal changes that occur in the tyrosine kinase receptor, epidermal growth
      factor receptor (EGFR), upon stimulation. Specifically A 431 cells were
      stimulated with epidermal growth factor after which EGFR was immunoprecipitated
      at stimulation times of 0, 0.5, 2, and 10 min as well as 4 h. High sequence
      coverage was obtained (96%), and methods were developed for label-free
      quantitation of phosphorylation and glycosylation. A total of 13 phosphorylation
      sites were identified, and the estimated stoichiometry was determined over the
      stimulation time points, including Thr(P) and Ser(P) sites in addition to Tyr(P)
      sites. A total of 10 extracellular domain N-glycan sites were also identified,
      and major glycoforms at each site were quantitated. No change in the extent of
      glycosylation with stimulation was observed as expected. Finally potential
      binding partners to EGFR were identified based on changes in the amount of
      protein pulled down with EGFR as a function of time of stimulation. Many of the
      19 proteins identified are known binding partners of EGFR. This work demonstrates
      that comprehensive characterization provides a powerful tool to aid in the study
      of important therapeutic targets. The detailed molecular information will prove
      useful in future studies in tissue.

PMID- 16799094
TI  - Cannabis and sport.
AB  - BACKGROUND AND OBJECTIVES: Cannabis is on the list of prohibited substances in
      the practice of sport, although its performance enhancing effect has not yet been
      proved. Its popularity among the younger generations as a social drug puts
      cannabis at the top of the list of compounds detected by the anti-doping
      laboratories accredited by the World Anti-Doping Agency worldwide. The management
      of the results of urine analysis is quite difficult for the medical and
      disciplinary committees not only because of the social use of the substance, but
      also because of the interpretation of the analytical data from urine samples.
      This paper gives an overview of what is presently known about cannabis in
      relation with the practice of sport. METHODS: Review of literature on the
      cannabis and exercise, its effect in the body, and the problems with
      interpretation of results when it is detected in urine. RESULTS: The paper
      outlines the major effects of cannabis in the context of its social use and its
      use for sport activities. The difficulties in the interpretation of urine sample
      analysis results because of the protracted excretion time of the main metabolite,
      long after the intake, are described. CONCLUSIONS: There is an urgent need for
      sport authorities to take measures necessary to avoid players misusing cannabis.

PMID- 16799095
TI  - Central nervous system stimulants and sport practice.
AB  - BACKGROUND AND OBJECTIVES: Central nervous system (CNS) stimulants may be used to
      reduce tiredness and increase alertness, competitiveness, and aggression. They
      are more likely to be used in competition but may be used during training to
      increase the intensity of the training session. There are several potential
      dangers involving their misuse in contact sports. This paper reviews the three
      main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in
      sport. METHODS: Description of the pharmacology, actions, and side effects of
      amfetamine, cocaine, and ephedrine. RESULTS: CNS stimulants have psychotropic
      effects that may be perceived to be ergogenic. Some are prescription drugs, such
      as Ephedra alkaloids, and there are issues regarding their appropriate
      therapeutic use. Recently attention has been given to their widespread use by
      athletes, despite the lack of evidence regarding any ergogenic or real
      performance benefit, and their potentially serious side effects. Recreational
      drugs, some of which are illegal (cocaine, amfetamines), are commonly used by
      athletes and cause potential ergolytic effects. Overall, these drugs are
      important for their frequent use and mention in anti-doping laboratories
      statistics and the media, and their potentially serious adverse effects.
      CONCLUSIONS: Doping with CNS stimulants is a real public health problem and all
      sports authorities should participate in its prevention. Dissemination of
      information is essential to prevent doping in sport and to provide alternatives.
      Adequate training and education in this domain should be introduced.

PMID- 16799096
TI  - The FIFA/F-MARC update on doping.

PMID- 16799097
TI  - Testosterone and doping control.
AB  - BACKGROUND AND OBJECTIVES: Anabolic steroids are synthetic derivatives of
      testosterone, modified to enhance its anabolic actions (promotion of protein
      synthesis and muscle growth). They have numerous side effects, and are on the
      International Olympic Committee's list of banned substances. Gas chromatography
      mass spectrometry allows identification and characterisation of steroids and
      their metabolites in the urine but may not distinguish between pharmaceutical and
      natural testosterone. Indirect methods to detect doping include determination of
      the testosterone/epitestosterone glucuronide ratio with suitable cut-off values.
      Direct evidence may be obtained with a method based on the determination of the
      carbon isotope ratio of the urinary steroids. This paper aims to give an overview
      of the use of anabolic-androgenic steroids in sport and methods used in anti
      doping laboratories for their detection in urine, with special emphasis on doping
      with testosterone. METHODS: Review of the recent literature of anabolic steroid
      testing, athletic use, and adverse effects of anabolic-androgenic steroids.
      RESULTS: Procedures used for detection of doping with endogenous steroids are
      outlined. The World Anti-Doping Agency provided a guide in August 2004 to ensure
      that laboratories can report, in a uniform way, the presence of abnormal profiles
      of urinary steroids resulting from the administration of testosterone or its
      precursors, androstenediol, androstenedione, dehydroepiandrosterone or a
      testosterone metabolite, dihydrotestosterone, or a masking agent,
      epitestosterone. CONCLUSIONS: Technology developed for detection of testosterone
      in urine samples appears suitable when the substance has been administered
      intramuscularly. Oral administration leads to rapid pharmacokinetics, so urine
      samples need to be collected in the initial hours after intake. Thus there is a
      need to find specific biomarkers in urine or plasma to enable detection of long
      term oral administration of testosterone.

PMID- 16799098
TI  - Significance of 19-norandrosterone in athletes' urine samples.
AB  - Nandrolone and other 19-norsteroid potent anabolic steroids have been prohibited
      in sports for 30 years. The detection of the main urinary metabolite--19
      norandrosterone--in amounts greater than 2 ng/ml constitutes an adverse
      analytical finding. The presence in nutritional sport supplements of steroids not
      listed on the label has undoubtedly resulted in positive tests, but inadvertent
      consumption of meat containing residues of hormonal treatment should not
      realistically cause apprehension. Although highly improbable, athletes should
      prudently avoid meals composed of pig offal in the hours preceding the test since
      the consumption of edible parts of a non-castrated pig, containing 19
      nortestosterone, has been shown to results in the excretion of 19-norandrosterone
      in the following hours. Norsteroid metabolites are formed during pregnancy and
      excreted as minor metabolites of norethisterone, and minute amounts have been
      identified in some male and female samples when using more sensitive techniques
      of detection. Whereas exercise does not seem to be a significant factor in 19
      norandrosterone excretion, some rare urine samples were found to be a suitable
      medium for in situ 19-demethylation of urinary metabolites.

PMID- 16799099
TI  - FIFA's approach to doping in football.
AB  - BACKGROUND AND OBJECTIVES: FIFA's anti-doping strategy relies on education and
      prevention. A worldwide network of physicians guarantees doping control
      procedures that are straightforward and leave no place for cheating. FIFA
      actively acknowledges its responsibility to protect players from harm and ensure
      equal chances for all competitors by stringent doping control regulations, data
      collection of positive samples, support of research, and collaboration with other
      organisations. This article aims to outline FIFA's approach to doping in
      football. METHOD: Description of FIFA's doping control regulations and
      procedures, statistical analysis of FIFA database on doping control, and
      comparison with data obtained by WADA accredited laboratories as for 2004.
      RESULTS: Data on positive doping samples per substance and confederation/nation
      documented at the FIFA medical office from 1994 to 2005 are provided. According
      to the FIFA database, the incidence of positive cases over the past 11 years was
      0.12%, with about 0.42% in 2004 (based on the assumption of 20,750 samples per
      year) and 0.37% in 2005. Especially important in this regard is the extremely low
      incidence of the true performance enhancing drugs such as anabolic steroids and
      stimulants. However, there is a need for more consistent data collection and
      cross checks among international anti-doping agencies as well as for further
      studies on specific substances, methods, and procedures. With regard to general
      health impairments in players, FIFA suggests that principles of occupational
      medicine should be considered and treatment with banned substances for purely
      medical reasons should be permitted to enable players to carry out their
      profession. At the same time, a firm stand has to be taken against suppression of
      symptoms by medication with the aim of meeting the ever increasing demands on
      football players. CONCLUSION: Incidence of doping in football seems to be low,
      but much closer collaboration and further investigation is needed with regard to
      banned substances, detection methods, and data collection worldwide.

PMID- 16799100
TI  - Erythropoietin and blood doping.
AB  - OBJECTIVE AND METHOD: To outline the direct and indirect approaches in the fight
      against blood doping in sports, the different strategies that have been used and
      are currently being used to fight efficiently against blood doping are presented
      and discussed. RESULTS AND CONCLUSIONS: The paper outlines the different
      approaches and diagnostic tools that some federations have to identify and target
      sports people demonstrating abnormal blood profiles. Originally blood tests were
      introduced for medical reasons and for limiting misuse of recombinant human
      erythropoietin (rHuEPO). In this way it became possible to prevent athletes with
      haematocrit levels well above normal, and potentially dangerous for their health,
      competing in sport. Today, with nearly a decade of blood testing experience,
      sports authorities should be familiar with some of the limitations and specially
      the ability of blood tests performed prior to competitions to fight efficiently
      against the misuse of rHuEPO, blood transfusion, and artificial haemoglobin.

PMID- 16799101
TI  - Human growth hormone doping in sport.
AB  - BACKGROUND AND OBJECTIVES: Recombinant human growth hormone (rhGH) has been on
      the list of forbidden substances since availability of its recombinant form
      improved in the early 1990s. Although its effectiveness in enhancing physical
      performance is still unproved, the compound is likely used for its potential
      anabolic effect on the muscle growth, and also in combination with other products
      (androgens, erythropoietin, etc.). The degree of similarity between the
      endogenous and the recombinant forms, the pulsatile secretion and marked
      interindividual variability makes detection of doping difficult. Two approaches
      proposed to overcome this problem are: the indirect method, which measures a
      combination of several factors in the biological cascade affected by
      administration of GH; and the direct method, which measures the difference
      between the circulating and the recombinant (represented by the unique 22 kD
      molecule) forms of GH. This article gives an overview of what is presently known
      about hGH in relation to sport. The available methods of detection are also
      evaluated. METHODS: Review of the literature on GH in relation to exercise, and
      its adverse effects and methods of detection when used for doping. RESULTS AND
      CONCLUSION: The main effects of exercise on hGH production and the use and
      effects of rhGH in athletes are discussed. Difficulties encountered by
      laboratories to prove misuse of this substance by both indirect and direct
      analyses are emphasised. The direct method currently seems to have the best
      reliability, even though the time window of detection is too short. hGH doping is
      a major challenge in the fight against doping. The effect of exercise on hGH and
      its short half-life are still presenting difficulties during doping analysis. To
      date the most promising method appears to be the direct approach utilising
      immunoassays.

PMID- 16799102
TI  - Therapeutic use exemption.
AB  - Football players who have either physical symptoms or disease after injury may
      need to be treated with specific medicines that are on the list of prohibited
      substances. Therapeutic use exemption may be granted to such players, in
      accordance with strictly defined criteria-these are presented in this article.
      Procedures of how to request for an abbreviated or a standard therapeutic use
      exemption are explained, and data on therapeutic use exemptions (UEFA and FIFA,
      2004 and 2005) are also presented.

PMID- 16799103
TI  - Inhaled beta2 agonists and performance in competitive athletes.
AB  - OBJECTIVES: To provide an overview of the current literature on the use of
      inhaled beta2 agonists in non-asthmatic competitive athletes, and to assess the
      performance enhancing effect of inhaled beta2 agonists. METHODS: Review of the
      literature. RESULTS: Twenty randomised, placebo controlled studies (19 double
      blind, one single blind) were located. Only three studies reported a performance
      enhancing effect of inhaled beta2 agonists. However, methodological shortcomings
      were most likely responsible for these findings (for example, non-elite athletes,
      inconsistent results in different tests, subgroups with above-average
      responsiveness). CONCLUSIONS: This review reveals that there is no ergogenic
      potential of inhaled beta2 agonists in non-asthmatic athletes. In view of the
      epidemiology of asthma in athletes and the considerable workload involved in
      provision of therapeutic use exemptions the inclusion of inhaled beta2 agonists
      on the list of prohibited substances should be reconsidered.

PMID- 16799104
TI  - Glucocorticosteroids in football: use and misuse.
AB  - BACKGROUND AND OBJECTIVES: Glucocorticosteroids are widely used in medicine and
      have shown unchallenged therapeutic potential in several chronic inflammatory and
      other diseases. They are also widely used in sports medicine for the treatment of
      conditions such as asthma and acute injuries. In fact, as banned substances, most
      requests for therapeutic use exemption concern glucocorticosteroids.
      Nevertheless, their beneficial effect in certain conditions in sports, where
      inflammation is only a secondary reaction, remains to be validated. This paper
      aimed to provide a comprehensive review of the literature covering the
      therapeutic use of glucocorticosteroids since 1977 in conditions ranging from
      chronic rheumatic illness to peritendinous or intra-articular injection in acute
      injuries. METHODS: Search of the medical literature published between 1977 and
      2006 using PubMed. Articles relevant to the question "When and if at all is the
      use of glucocorticosteroids justified in football?" were selected and analysed.
      RESULTS AND CONCLUSIONS: The findings clearly point out that, despite the common
      use of glucocorticosteroids in acute injuries in sports, there is actually
      limited evidence of the true benefits of such a practice. Physicians must take
      the possible adverse effects into consideration. In an athlete with clinically
      verified asthma, inhalational glucocorticosteroids remain first line therapy.
      Finally, for the purposes of education and prevention of misuse, it should be
      stressed that a measurable performance enhancing effect of glucocorticoids could
      not be proved on the basis of the results of the scientific studies to date.

PMID- 16799105
TI  - Medicolegal aspects of doping in football.
AB  - This article describes the historical background of the medicolegal aspects of
      doping in sports and especially in football. The definitions of legal terms are
      explained and the procedure of individual case management as part of FIFA's
      approach to doping is presented. Finally, three medicolegal problems awaiting
      urgent solution are outlined: firstly, the difficulties in decision making
      arising from the decrease of the T/E ratio from 6 to 4; secondly, the therapeutic
      application of alpha-reductase inhibitors for male pattern baldness in the face
      of the classification of finasteride as a forbidden masking agent; and lastly,
      the increasing use of recreational drugs and its social and legal implications in
      positive cases.

PMID- 16799106
TI  - FIFA's future activities in the fight against doping.

PMID- 16799107
TI  - Take nothing but pictures, leave nothing but footprints...?

PMID- 16799108
TI  - Opening the Chamber of secrets: our response to "the end of the beginning".

PMID- 16799109
TI  - Case proven: exercise associated hyponatraemia is due to overdrinking. So why did
      it take 20 years before the original evidence was accepted?

PMID- 16799111
TI  - Strategies for the prevention of volleyball related injuries.
AB  - Although the overall injury rate in volleyball and beach volleyball is relatively
      low compared with other team sports, injuries do occur in a discipline specific
      pattern. Epidemiological research has revealed that volleyball athletes are, in
      general, at greatest risk of acute ankle injuries and overuse conditions of the
      knee and shoulder. This structured review discusses both the known and suspected
      risk factors and potential strategies for preventing the most common volleyball
      related injuries: ankle sprains, patellar tendinopathy, and shoulder overuse.

PMID- 16799110
TI  - Is fatigue all in your head? A critical review of the central governor model.
AB  - The central governor model has recently been proposed as a general model to
      explain the phenomenon of fatigue. It proposes that the subconscious brain
      regulates power output (pacing strategy) by modulating motor unit recruitment to
      preserve whole body homoeostasis and prevent catastrophic physiological failure
      such as rigor. In this model, the word fatigue is redefined from a term that
      describes an exercise decline in the ability to produce force and power to one of
      sensation or emotion. The underpinnings of the central governor model are the
      refutation of what is described variously as peripheral fatigue, limitations
      models, and the cardiovascular/anaerobic/catastrophe model. This argument centres
      on the inability of lactic acid models of fatigue to adequately explain fatigue.
      In this review, it is argued that a variety of peripheral factors other than
      lactic acid are known to compromise muscle force and power and that these effects
      may protect against "catastrophe". Further, it is shown that a variety of studies
      indicate that fatigue induced decreases in performance cannot be adequately
      explained by the central governor model. Instead, it is suggested that the
      concept of task dependency, in which the mechanisms of fatigue vary depending on
      the specific exercise stressor, is a more comprehensive and defensible model of
      fatigue. This model includes aspects of both central and peripheral contributions
      to fatigue, and the relative importance of each probably varies with the type of
      exercise.

PMID- 16799112
TI  - Anthropometric and physiological characteristics of junior elite volleyball
      players.
AB  - OBJECTIVES: To investigate the anthropometric and physiological characteristics
      of junior elite volleyball players. METHOD: Twenty five national level volleyball
      players (mean (SD) age 17.5 (0.5) years) were assessed on a number of
      physiological and anthropometric variables. Somatotype was assessed using the
      Heath-Carter method, body composition (% body fat, % muscle mass) was assessed
      using surface anthropometry, leg strength was assessed using a leg and back
      dynamometer, low back and hamstring flexibility was assessed using the sit and
      reach test, and the vertical jump was used as a measure of lower body power.
      Maximal oxygen uptake was predicted using the 20 m multistage fitness test.
      RESULTS: Setters were more ectomorphic (p<0.05) and less mesomorphic (p<0.01)
      than centres. Mean (SD) of somatotype (endomorphy, mesomorphy, ectomorphy) for
      setters and centres was 2.6 (0.9), 1.9 (1.1), 5.3 (1.2) and 2.2 (0.8), 3.9 (1.1),
      3.6 (0.7) respectively. Hitters had significantly greater low back and hamstring
      flexibility than opposites. Mean (SD) for sit and reach was 19.3 (8.3) cm for
      opposites and 37 (10.7) cm for hitters. There were no other significant
      differences in physiological and anthropometric variables across playing
      positions (all p>0.05). CONCLUSION: Setters tend to be endomorphic ectomorphs,
      hitters and opposites tend to be balanced ectomorphs, whereas centres tend to be
      ectomorphic mesomorphs. These results indicate the need for sports scientists and
      conditioning professionals to take the body type of volleyball players into
      account when designing individualised position specific training programmes.

PMID- 16799113
TI  - Calcific tendonitis of the quadriceps.
AB  - The case reported is of a 46 year old male who presented with a history of acute
      on chronic knee pain. The clinical features and investigations suggested a tear
      of the quadriceps tendon, with pre-existing chronic calcific enthesopathy. The
      operative findings were of an acute collection of calcific material within the
      quadriceps tendon. This acute presentation and calcific collection have not
      previously been reported in the quadriceps tendon.

PMID- 16799114
TI  - Does changing the configuration of a motor racing circuit make it safer?

PMID- 16799115
TI  - The story behind the development of the first whole-body computerized tomography
      scanner as told by Robert S. Ledley.

PMID- 16799117
TI  - Human and automated coding of rehabilitation discharge summaries according to the
      International Classification of Functioning, Disability, and Health.
AB  - OBJECTIVE: The International Classification of Functioning, Disability, and
      Health (ICF) is designed to provide a common language and framework for
      describing health and health-related states. The goal of this research was to
      investigate human and automated coding of functional status information using the
      ICF framework. DESIGN: The authors extended an existing natural language
      processing (NLP) system to encode rehabilitation discharge summaries according to
      the ICF. MEASUREMENTS: The authors conducted a formal evaluation, comparing the
      coding performed by expert coders, non-expert coders, and the NLP system.
      RESULTS: Automated coding can be used to assign codes using the ICF, with results
      similar to those obtained by human coders, at least for the selection of ICF code
      and assignment of the performance qualifier. Coders achieved high agreement on
      ICF code assignment. CONCLUSION: This research is a key next step in the
      development of the ICF as a sensitive and universal classification of functional
      status information. It is worthwhile to continue to investigate automated ICF
      coding.

PMID- 16799119
TI  - The CMIO--a new leader for health systems.
AB  - Physician leadership is a critical success factor for health information
      technology initiatives, but best practices for structuring the role and skills
      required for such leadership remain undefined. The authors conducted structured
      interviews with five physician information technology leaders, or Chief Medical
      Information Officers (CMIOs), at health systems that broadly used health
      information technology. The study aimed to identify the individual skills and
      organizational structure necessary for a CMIO to be effective. The interviews
      found that the CMIOs had significant management experience prior to serving as a
      CMIO and were positioned and supported within each health system similar to other
      executive leaders; only one of the five CMIOs had formal informatics training. A
      review of the findings advocates for the CMIO to have a strong background and
      role as a physician executive supported by knowledge in informatics, as opposed
      to being a highly trained informaticist with secondary management expertise or
      support.

PMID- 16799120
TI  - Development and testing of a scale to assess physician attitudes about handheld
      computers with decision support.
AB  - OBJECTIVE: The authors developed and evaluated a rating scale, the Attitudes
      toward Handheld Decision Support Software Scale (H-DSS), to assess physician
      attitudes about handheld decision support systems. DESIGN: The authors conducted
      a prospective assessment of psychometric characteristics of the H-DSS including
      reliability, validity, and responsiveness. Participants were 82 Internal Medicine
      residents. A higher score on each of the 14 five-point Likert scale items
      reflected a more positive attitude about handheld DSS. The H-DSS score is the
      mean across the fourteen items. Attitudes toward the use of the handheld DSS were
      assessed prior to and six months after receiving the handheld device. STATISTICS:
      Cronbach's Alpha was used to assess internal consistency reliability. Pearson
      correlations were used to estimate and detect significant associations between
      scale scores and other measures (validity). Paired sample t-tests were used to
      test for changes in the mean attitude scale score (responsiveness) and for
      differences between groups. RESULTS: Internal consistency reliability for the
      scale was alpha = 0.73. In testing validity, moderate correlations were noted
      between the attitude scale scores and self-reported Personal Digital Assistant
      (PDA) usage in the hospital (correlation coefficient = 0.55) and clinic (0.48), p
      < 0.05 for both. The scale was responsive, in that it detected the expected
      increase in scores between the two administrations (3.99 (s.d. = 0.35) vs. 4.08,
      (s.d. = 0.34), p < 0.005). CONCLUSION: The authors' evaluation showed that the H
      DSS scale was reliable, valid, and responsive. The scale can be used to guide
      future handheld DSS development and implementation.

PMID- 16799121
TI  - Use of SNOMED CT to represent clinical research data: a semantic characterization
      of data items on case report forms in vasculitis research.
AB  - OBJECTIVE: To estimate the coverage provided by SNOMED CT for clinical research
      concepts represented by the items on case report forms (CRFs), as well as the
      semantic nature of those concepts relevant to post-coordination methods. DESIGN:
      Convenience samples from CRFs developed by rheumatologists conducting several
      longitudinal, observational studies of vasculitis were selected. A total of 17
      CRFs were used as the basis of analysis for this study, from which a total set of
      616 (unique) items were identified. Each unique data item was classified as
      either a clinical finding or procedure. The items were coded by the presence and
      nature of SNOMED CT coverage and classified into semantic types by 2 coders.
      MEASUREMENTS: Basic frequency analysis was conducted to determine levels of
      coverage provided by SNOMED CT. Estimates of coverage by various semantic
      characterizations were estimated. RESULTS: Most of the core clinical concepts
      (88%) from these clinical research data items were covered by SNOMED CT; however,
      far fewer of the concepts were fully covered (that is, where all aspects of the
      CRF item could be represented completely without post-coordination; 23%). In
      addition, a large majority of the concepts (83%) required post-coordination,
      either to clarify context (e.g., time) or to better capture complex clinical
      concepts (e.g., disease-related findings). For just over one third of the sampled
      CRF data items, both types of post-coordination were necessary to fully represent
      the meaning of the item. CONCLUSION: SNOMED CT appears well-suited for
      representing a variety of clinical concepts, yet is less suited for representing
      the full amount of information collected on CRFs.

PMID- 16799122
TI  - Quantitative assessment of dictionary-based protein named entity tagging.
AB  - OBJECTIVE: Natural language processing (NLP) approaches have been explored to
      manage and mine information recorded in biological literature. A critical step
      for biological literature mining is biological named entity tagging (BNET) that
      identifies names mentioned in text and normalizes them with entries in biological
      databases. The aim of this study was to provide quantitative assessment of the
      complexity of BNET on protein entities through BioThesaurus, a thesaurus of
      gene/protein names for UniProt knowledgebase (UniProtKB) entries that was
      acquired using online resources. METHODS: We evaluated the complexity through
      several perspectives: ambiguity (i.e., the number of genes/proteins represented
      by one name), synonymy (i.e., the number of names associated with the same
      gene/protein), and coverage (i.e., the percentage of gene/protein names in text
      included in the thesaurus). We also normalized names in BioThesaurus and measures
      were obtained twice, once before normalization and once after. RESULTS: The
      current version of BioThesaurus has over 2.6 million names or 2.1 million
      normalized names covering more than 1.8 million UniProtKB entries. The average
      synonymy is 3.53 (2.86 after normalization), ambiguity is 2.31 before
      normalization and 2.32 after, while the coverage is 94.0% based on the
      BioCreAtive data set comprising MEDLINE abstracts containing genes/proteins.
      CONCLUSION: The study indicated that names for genes/proteins are highly
      ambiguous and there are usually multiple names for the same gene or protein. It
      also demonstrated that most gene/protein names appearing in text can be found in
      BioThesaurus.

PMID- 16799123
TI  - Improving efficacy of PubMed Clinical Queries for retrieving scientifically
      strong studies on treatment.
AB  - The authors evaluated the retrieval power of PubMed "Clinical Queries," narrow
      search string, about therapy in comparison with a modified search string to avoid
      possible retrieval bias. PubMed search strategy was compared to a slightly
      modified string that included the Britannic English term "randomised." The
      authors tested the two strings joined onto each of four terms concerning topics
      of broad interest: hypertension, hepatitis, diabetes, and heart failure. In
      particular, precision was computed for not-indexed citations. The added word
      "randomised" improved total citation retrieval in any case. Total retrieval gain
      for not-indexed citations ranged from 11.1% to 21.4%. A significant number of
      Randomized Controlled Trial(s) (RCT)s (9.1-18.2%) was retrieved for each of the
      selected topics. They were often recently published RCTs. The authors think that
      correction of the Clinical Queries filter (when they focus on therapy and use
      narrow searches) is necessary to avoid biased search results with loss of
      relevant and up-to-date scientifically sound information.

PMID- 16799124
TI  - Advancing biomedical image retrieval: development and analysis of a test
      collection.
AB  - OBJECTIVE: Develop and analyze results from an image retrieval test collection.
      METHODS: After participating research groups obtained and assessed results from
      their systems in the image retrieval task of Cross-Language Evaluation Forum, we
      assessed the results for common themes and trends. In addition to overall
      performance, results were analyzed on the basis of topic categories (those most
      amenable to visual, textual, or mixed approaches) and run categories (those
      employing queries entered by automated or manual means as well as those using
      visual, textual, or mixed indexing and retrieval methods). We also assessed
      results on the different topics and compared the impact of duplicate relevance
      judgments. RESULTS: A total of 13 research groups participated. Analysis was
      limited to the best run submitted by each group in each run category. The best
      results were obtained by systems that combined visual and textual methods. There
      was substantial variation in performance across topics. Systems employing textual
      methods were more resilient to visually oriented topics than those using visual
      methods were to textually oriented topics. The primary performance measure of
      mean average precision (MAP) was not necessarily associated with other measures,
      including those possibly more pertinent to real users, such as precision at 10 or
      30 images. CONCLUSIONS: We developed a test collection amenable to assessing
      visual and textual methods for image retrieval. Future work must focus on how
      varying topic and run types affect retrieval performance. Users' studies also are
      necessary to determine the best measures for evaluating the efficacy of image
      retrieval systems.

PMID- 16799125
TI  - Automating the assignment of diagnosis codes to patient encounters using example
      based and machine learning techniques.
AB  - OBJECTIVE: Human classification of diagnoses is a labor intensive process that
      consumes significant resources. Most medical practices use specially trained
      medical coders to categorize diagnoses for billing and research purposes.
      METHODS: We have developed an automated coding system designed to assign codes to
      clinical diagnoses. The system uses the notion of certainty to recommend
      subsequent processing. Codes with the highest certainty are generated by matching
      the diagnostic text to frequent examples in a database of 22 million manually
      coded entries. These code assignments are not subject to subsequent manual
      review. Codes at a lower certainty level are assigned by matching to previously
      infrequently coded examples. The least certain codes are generated by a naive
      Bayes classifier. The latter two types of codes are subsequently manually
      reviewed. MEASUREMENTS: Standard information retrieval accuracy measurements of
      precision, recall and f-measure were used. Micro- and macro-averaged results were
      computed. RESULTS At least 48% of all EMR problem list entries at the Mayo Clinic
      can be automatically classified with macro-averaged 98.0% precision, 98.3% recall
      and an f-score of 98.2%. An additional 34% of the entries are classified with
      macro-averaged 90.1% precision, 95.6% recall and 93.1% f-score. The remaining 18%
      of the entries are classified with macro-averaged 58.5%. CONCLUSION: Over two
      thirds of all diagnoses are coded automatically with high accuracy. The system
      has been successfully implemented at the Mayo Clinic, which resulted in a
      reduction of staff engaged in manual coding from thirty-four coders to seven
      verifiers.

PMID- 16799126
TI  - Estimating development cost for a tailored interactive computer program to
      enhance colorectal cancer screening compliance.
AB  - The authors used an actual-work estimate method to estimate the cost of
      developing a tailored interactive computer education program to improve
      compliance with colorectal cancer screening guidelines in a large multi-specialty
      group medical practice. Resource use was prospectively collected from time logs,
      administrative records, and a design and computing subcontract. Sensitivity
      analysis was performed to examine the uncertainty of the overhead cost rate and
      other parameters. The cost of developing the system was Dollars 328,866. The
      development cost was Dollars 52.79 per patient when amortized over a 7-year
      period with a cohort of 1,000 persons. About 20% of the cost was incurred in
      defining the theoretic framework and supporting literature, constructing the
      variables and survey, and conducting focus groups. About 41% of the cost was for
      developing the messages, algorithms, and constructing program elements, and the
      remaining cost was to create and test the computer education program. About 69%
      of the cost was attributable to personnel expenses. Development cost is rarely
      estimated but is important for feasibility studies and ex-ante economic
      evaluations of alternative interventions. The findings from this study may aid
      decision makers in planning, assessing, budgeting, and pricing development of
      tailored interactive computer-based interventions.

PMID- 16799127
TI  - Enhancing text categorization with semantic-enriched representation and training
      data augmentation.
AB  - OBJECTIVE: Acquiring and representing biomedical knowledge is an increasingly
      important component of contemporary bioinformatics. A critical step of the
      process is to identify and retrieve relevant documents among the vast volume of
      modern biomedical literature efficiently. In the real world, many information
      retrieval tasks are difficult because of high data dimensionality and the lack of
      annotated examples to train a retrieval algorithm. Under such a scenario, the
      performance of information retrieval algorithms is often unsatisfactory,
      therefore improvements are needed. DESIGN: We studied two approaches that enhance
      the text categorization performance on sparse and high data dimensionality: (1)
      semantic-preserving dimension reduction by representing text with semantic
      enriched features; and (2) augmenting training data with semi-supervised
      learning. A probabilistic topic model was applied to extract major semantic
      topics from a corpus of text of interest. The representation of documents was
      projected from the high-dimensional vocabulary space onto a semantic topic space
      with reduced dimensionality. A semi-supervised learning algorithm based on graph
      theory was applied to identify potential positive training cases, which were
      further used to augment training data. The effects of data transformation and
      augmentation on text categorization by support vector machine (SVM) were
      evaluated. RESULTS AND CONCLUSION: Semantic-enriched data transformation and the
      pseudo-positive-cases augmented training data enhance the efficiency and
      performance of text categorization by SVM.

PMID- 16799128
TI  - Types of unintended consequences related to computerized provider order entry.
AB  - OBJECTIVE: To identify types of clinical unintended adverse consequences
      resulting from computerized provider order entry (CPOE) implementation. DESIGN:
      An expert panel provided initial examples of adverse unintended consequences of
      CPOE. The authors, using qualitative methods, gathered and analyzed additional
      examples from five successful CPOE sites. METHODS: Using a card sort method, the
      authors developed a categorization scheme for the 79 unintended consequences
      initially identified and then iteratively modified the scheme to categorize 245
      additional adverse consequences resulting from fieldwork. Because the focus
      centered on consequences requiring prevention or remedial action, the authors did
      not further analyze reported unintended beneficial (positive) consequences.
      RESULTS: Unintended adverse consequences (UACs) fell into nine major categories
      (in order of decreasing frequency): 1) more/new work for clinicians; 2)
      unfavorable workflow issues; 3) never ending system demands; 4) problems related
      to paper persistence; 5) untoward changes in communication patterns and
      practices; 6) negative emotions; 7) generation of new kinds of errors; 8)
      unexpected changes in the power structure; and 9) overdependence on the
      technology. Clinical decision support features introduced many of these
      unintended consequences. CONCLUSION: Identifying and understanding the types and
      in some instances the causes of unintended adverse consequences associated with
      CPOE will enable system developers and implementers to better manage
      implementation and maintenance of future CPOE projects.

PMID- 16799129
TI  - e-Prescribing, efficiency, quality: lessons from the computerization of UK family
      practice.
AB  - Nearly all general practice physicians (GPs) in the United Kingdom (UK) have
      electronic health record (EHR) systems in their practices compared with perhaps
      15% of primary care physicians in the United States (U.S.). Based on interviews
      of 13 general GPs and review of current literature, the authors argue that the
      historical experience of widespread electronic health record uptake in the UK
      provides insight into features that might motivate broad adoption in the United
      States. These features include electronic prescribing, improved quality and
      consistency of care, practice efficiencies that have both timesaving and revenue
      generating effects, and potential shielding from malpractice claims.

PMID- 16799130
TI  - A risk assessment of two interorganizational clinical information systems.
AB  - A risk analysis framework was used to examine the implementation barriers that
      may hamper the successful implementation of interorganizational clinical
      information systems (ICIS). In terms of study design, an extensive literature
      review was first performed in order to elaborate a comprehensive model of project
      risk factors. To test the applicability of the model, we next conducted a
      longitudinal multiple-case study of two large-scale ICIS demonstration projects
      carried out in Quebec, Canada. Variations in the levels of several risk
      dimensions measured throughout the duration of the projects were analyzed to
      determine their impact on successful implementation. The analysis shows that the
      proposed framework, composed of five risk dimensions, was very robust, and
      suitable for conducting a thorough risk analysis. The results also show that
      there are links between the quality of the risk management and the level of
      project outcomes. To be successful, it is important that the implementation
      efforts be distributed proportionally according to the importance of each of the
      risk factors. Furthermore, because the risks evolve dynamically, there is a need
      for high responsiveness to emerging implementation problems. Thus, implementation
      success lies in the ability of the project management team to be aware of and to
      manage several risk threats simultaneously and coherently since they evolve
      dynamically through time and interact with one another.

PMID- 16799131
TI  - Pioglitazone induces apoptosis of macrophages in human adipose tissue.
AB  - Metabolic syndrome and type 2 diabetes mellitus are associated with an increased
      number of macrophage cells that infiltrate white adipose tissue (WAT).
      Previously, we demonstrated that the treatment of subjects with impaired glucose
      tolerance (IGT) with the peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist pioglitazone resulted in a decrease in macrophage number in
      adipose tissue. Here, adipose tissue samples from IGT subjects treated with
      pioglitazone were examined for apoptosis with terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. TUNEL
      positive cells were identified, and there was a significant 42% increase in TUNEL
      positive cells following pioglitazone treatment. Overlay experiments with anti
      CD68 antibody demonstrated that most of the TUNEL-positive cells were
      macrophages. To determine whether macrophage apoptosis was a direct or indirect
      effect of pioglitazone treatment, human THP1 cells were treated with pioglitazone
      in vitro, demonstrating increased TUNEL staining in a dose- and time-dependent
      manner. Furthermore, the appearance of the active proteolytic subunits of caspase
      3 and caspase-9 were detected in cell lysate from THP1 cells and also increased
      in a dose- and time-dependent manner following pioglitazone treatment.
      Pretreatment with a PPARgamma inhibitor, GW9662, prevented pioglitazone induction
      of the apoptotic pathway in THP1 cells. Differentiated human adipocytes did not
      show any significant increase in apoptosis after treatment in vitro with
      piolgitazone. These findings indicate that PPARgamma has distinct functions in
      different cell types in WAT, such that pioglitazone reduces macrophage
      infiltration by inducing apoptotic cell death specifically in macrophages through
      PPARgamma activation.

PMID- 16799132
TI  - Protection from contraction-induced injury provided to skeletal muscles of young
      and old mice by passive stretch is not due to a decrease in initial mechanical
      damage.
AB  - Contraction-induced injury occurs when muscles are stretched while activated
      (lengthening contractions). The injury is initiated by mechanical damage followed
      by an inflammatory response. Old animals are particularly susceptible to
      contraction-induced injury, yet exposure to stretches without activation (passive
      stretches) before lengthening contractions lessens the injury. We hypothesized
      that, for muscles of both young and old mice, prior exposure to passive stretches
      reduces the initial mechanical damage induced by lengthening contractions.
      Compared with unconditioned muscles in both age groups, administration of passive
      stretches 1 hour before lengthening contractions decreased the force deficit at 3
      days by one half, but did not affect the force deficit at 10 minutes. Force
      deficits immediately after two lengthening contractions were also not different
      for passive stretch-conditioned and unconditioned muscles. The similarity in
      force deficits immediately following lengthening contractions for conditioned and
      unconditioned muscle indicates that passive stretch conditioning does not
      decrease initial mechanical damage in young or old mice.

PMID- 16799133
TI  - Effects of exercise on mitochondrial content and function in aging human skeletal
      muscle.
AB  - Skeletal muscle mitochondria are implicated with age-related loss of function and
      insulin resistance. We examined the effects of exercise on skeletal muscle
      mitochondria in older (age = 67.3 +/- 0.6 years) men (n = 5) and women (n = 3).
      Similar increases in (p <.01) cardiolipin (88.2 +/- 9.0 to 130.6 +/- 7.5
      microg/mU creatine kinase activity [CK]) and the total mitochondrial DNA (1264 +/
      170 to 1895 +/- 273 copies per diploid of nuclear genome) reflected increased
      mitochondria content. Succinate oxidase activity, complexes 2-4 of the electron
      transport chain (ETC), increased from 0.13 +/- 0.02 to 0.20 +/- 0.02 U/mU CK (p
      <.01). This improvement was more pronounced (p <.05) in subsarcolemmal (127 +/-
      48%) compared to intermyofibrillar (56 +/- 12%) mitochondria. NADH oxidase
      activity, representing total ETC activity, increased from 0.51 +/- 0.09 to 1.00
      +/- 0.09 U/mU CK (p <.01). In conclusion, exercise enhances mitochondria ETC
      activity in older human skeletal muscle, particularly in subsarcolemmal
      mitochondria, which is likely related to the concomitant increases in
      mitochondrial biogenesis.

PMID- 16799134
TI  - Paraoxonase activity and genotype predispose to successful aging.
AB  - The paraoxonase 1 codon 192 R allele has been previously reported to have a role
      in successful aging. The relationship between PON1 genotypes, enzymatic activity,
      and mass concentration was evaluated in a group of 229 participants from 22 to
      104 years of age, focusing our attention on nonagenarian/centenarian
      participants. We found a genetic control for paraoxonase activity that is
      maintained throughout life, also in the nonagenarians/centenarians. This activity
      decreases significantly during aging and shows different mean values among R and
      M carriers, where R+ and M- carriers have the significant highest paraoxonase
      activity. Results from the multinomial regression logistic model show that
      paraoxonase activity as well as R+ and M- carriers contribute significantly to
      the explanation of the longevity phenotype. In conclusion, we show that genetic
      variability at the PON1 locus is related to paraoxonase activity throughout life,
      and suggest that both parameters affect survival at extreme advanced age.

PMID- 16799135
TI  - A polymorphism of the YTHDF2 gene (1p35) located in an Alu-rich genomic domain is
      associated with human longevity.
AB  - The uneven distribution of Alu repetitive elements in the human genome is related
      to specific functional properties of genomic regions. We report the
      identification of a locus associated with human longevity in one of the
      chromosomal regions with the highest density of Alu elements, in 1p35. The locus,
      corresponding to a (TG)n microsatellite in the YTHDF2 gene, was identified by
      characterizing an "anonymous" marker detectable through inter-Alu fingerprinting,
      which previously evidenced an increased homozygosity in centenarians. After
      genotyping 412 participants of different ages, including 137 centenarians, we
      confirmed the increased homozygosity in centenarians at this locus, and observed
      a concomitantly increased frequency of the most frequent allele and the
      corresponding homozygous genotype. Remarkably, the same genotype was associated
      with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. Finally,
      YTHDF2 messenger RNA resulted to be mainly expressed in testis and placenta. The
      data suggest a possible role of this locus in human longevity.

PMID- 16799136
TI  - Is (your cellular response to) stress killing you?
AB  - Free radicals provide a generally accepted explanation for age-related decline in
      tissue function. However, the free radical hypothesis does not provide a
      mechanistic course of action to explain exactly how damage to macromolecules
      translates into the recognizable pathophysiology of aged organisms. Recent
      advances in the fields of DNA damage and cellular senescence point towards a
      substantial role for the DNA damage response, rather than DNA mutations per se,
      in the genesis of cellular and/or tissue damage. Furthermore, several studies
      suggest that protein damage can be at least as important as DNA damage in
      bringing about the aging phenotype. Here we propose that a "protein damage
      response," namely the ER/UPR (endoplasmic reticulum/unfolded protein) stress
      response is likely to play an important role in the aging process.

PMID- 16799137
TI  - Long-lived growth hormone receptor knockout mice show a delay in age-related
      changes of body composition and bone characteristics.
AB  - There is conflicting information on the physiological role of growth hormone (GH)
      in the control of aging. This study reports dual-energy x-ray absorptiometry
      (DXA) measurements of body composition and bone characteristics in young, adult,
      and aged long-lived GH receptor knockout (GHR-KO) and normal mice to determine
      the effects of GH resistance during aging. Compared to controls, GHR-KO mice
      showed an increased percentage of body fat. GHR-KO mice have reduced total-body
      bone mineral density (BMD), bone mineral content, and bone area, but these
      parameters increased with age. In addition, GHR-KO mice have decreased femur
      length, femur BMD, and lower lumbar BMD compared to controls in all age groups.
      These parameters also continued to increase with age. Our results indicate that
      GH resistance alters body composition, bone growth, and bone maintenance during
      aging in GHR-KO mice.

PMID- 16799138
TI  - Age-related accumulation of a novel CD44 + CD25lowgammadelta T-cell population in
      hematopoietic organs of the mouse.
AB  - We discovered a novel population of gammadelta T cells in the mouse that
      accumulates with age in hematopoietic organs, but not in epithelia. These cells
      are CD25low (an unusual phenotype for gammadelta T cells in the mouse); express
      higher levels of TCRgammadelta and CD44 than do CD25- gammadelta T cells; mainly
      express Vgamma2, Vgamma3, and Vgamma4 chains; and are largely quiescent. A very
      similar cell population appears in the late stages of fetal thymus organ
      cultures, suggesting that the accumulation of CD44 + CD25lowTCRgammadelta + cells
      is a response to stress induced by aging in vivo or by culture in vitro. The
      precursors of CD44 + CD25lowTCRgammadelta + cells are generated during fetal or
      very young adult life, as this population was undetectable in aged recipients of
      bone marrow from old or young donors. CD44 + CD25lowTCRgammadelta + cells may be
      a biomarker of aging, but could also play a role in the inflammatory changes that
      accompany aging.

PMID- 16799140
TI  - The effect of undernutrition in the development of frailty in older persons.

PMID- 16799141
TI  - Low nutrient intake is an essential component of frailty in older persons.
AB  - BACKGROUND: Poor nutrient intake is conceptualized to be a component of frailty,
      but this hypothesis has been little investigated. We examined the association
      between low energy and nutrient intake and frailty. METHODS: We used data from
      802 persons aged 65 years or older participating to the InCHIANTI (Invecchiare in
      Chianti, aging in the Chianti area) study. Frailty was defined by having at least
      two of the following criteria: low muscle strength, feeling of exhaustion, low
      walking speed, and reduced physical activity. The European Prospective
      Investigation into Cancer and nutrition (EPIC) questionnaire was used to estimate
      the daily intake of energy and nutrients. Low intake was defined using the value
      corresponding to the lowest sex-specific intake quintile of energy and specific
      nutrients. Adjusted logistic regression analyses were used to study the
      association of frailty and frailty criteria with low intakes of energy and
      nutrients. RESULTS: Daily energy intake < or =21 kcal/kg was significantly
      associated with frailty (odds ratio [OR]: 1.24; 95% CI: 1.02-1.5). After
      adjusting for energy intake, a low intake of protein (OR: 1.98; 95% CI: 1.18
      3.31); vitamins D (OR: 2.35; 95% CI: 1.48-3.73), E (OR: 2.06; 95% CI: 1.28-3.33),
      C (OR: 2.15; 95% CI: 1.34-3.45), and folate (OR: 1.84; 95% CI: 1.14-2.98); and
      having a low intake of more than three nutrients (OR: 2.12; 95% CI: 1.29-3.50)
      were significantly and independently related to frailty. CONCLUSIONS: This study
      provides evidence that low intakes of energy and selected nutrients are
      independently associated with frailty.

PMID- 16799139
TI  - Interleukin-6 in aging and chronic disease: a magnificent pathway.
AB  - The human interleukin IL-6 was originally cloned in 1986. In 1993, William
      Ershler, in his article "IL-6: A Cytokine for Gerontologists," indicated IL-6 as
      one of the main signaling pathways modulating the complex relationship between
      aging and chronic morbidity. Over the last 12 years, our understanding of the
      role of IL-6 in human physiology and pathology has substantially grown, although
      some of the questions originally posed by Ershler are still debated. In this
      review, we will focus on IL-6 structure, IL-6 signaling, and trans signaling
      pathways, and the role of IL-6 in geriatric syndromes and chronic disease. In the
      final section of this review, we dissect the critical elements of the IL-6
      signaling pathway and point out targets for intervention that are targeted by
      emerging drugs, some still on the horizon and others already being tested in
      clinical trials.

PMID- 16799142
TI  - Low serum micronutrient concentrations predict frailty among older women living
      in the community.
AB  - BACKGROUND: Micronutrient deficiencies are common among older adults. We
      hypothesized that low serum micronutrient concentrations were predictive of
      frailty among older disabled women living in the community. METHODS: We studied
      766 women, aged 65 and older, from the Women's Health and Aging Study I, a
      population-based study of moderately to severely disabled community-dwelling
      women in Baltimore, Maryland. Serum vitamins A, D, E, B(6), and B(12),
      carotenoids, folate, zinc, and selenium were measured at baseline. Frailty status
      was determined at baseline and during annual visits for 3 years of follow-up.
      RESULTS: At baseline, 250 women were frail and 516 women were not frail. Of 463
      nonfrail women who had at least one follow-up visit, 205 (31.9%) became frail,
      with an overall incidence rate of 19.1 per 100 person-years. Compared with women
      in the upper three quartiles, women in the lowest quartile of serum carotenoids
      (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.01-1.92), alpha
      tocopherol (HR 1.39; 95% CI, 1.02-1.92), and 25-hydroxyvitamin D (HR 1.34; 95%
      CI, 0.94-1.90) had an increased risk of becoming frail. The number of nutritional
      deficiencies (HR 1.10; 95% CI, 1.01-1.20) was associated with an increased risk
      of becoming frail, after adjusting for age, smoking status, and chronic pulmonary
      disease. Adjusting for potential confounders, we found that women in the lowest
      quartile of serum carotenoids had a higher risk of becoming frail (HR 1.54; 95%
      CI, 1.11-2.13). CONCLUSIONS: Low serum micronutrient concentrations are an
      independent risk factor for frailty among disabled older women, and the risk of
      frailty increases with the number of micronutrient deficiencies.

PMID- 16799143
TI  - Vitamin and carotenoid status in older women: associations with the frailty
      syndrome.
AB  - OBJECTIVE: We investigated the relationship of micronutrient deficiencies with
      the frailty syndrome in older women living in the community. METHODS: Frailty
      status and serum micronutrients were assessed in a cross-sectional study of 754
      women, 70-80 years old, from the Women's Health and Aging Studies I and II.
      RESULTS: Among nonfrail, prefrail, and frail women, respectively, geometric mean
      serum concentrations were 1.842, 1.593, and 1.376 micromol/L for total
      carotenoids (p <.001); 2.66, 2.51, and 2.43 micromol/L for retinol (p =.04);
      50.9, 47.4, and 43.8 nmol/L for 25-hydroxyvitamin D (p =.019); 43.0, 35.8, and
      30.9 nmol/L for vitamin B(6) (p =.002); and 10.2, 9.3, and 8.7 ng/mL for folate
      (p =.03). Frail women were more likely to have at least two or more micronutrient
      deficiencies (p =.05). The age-adjusted odds ratios of being frail were
      significantly higher for those participants whose micronutrient concentrations
      were in the lowest quartile compared to the top three quartiles for total
      carotenoids, alpha-tocopherol, 25-hydroxyvitamin D, and vitamin B(6). The
      association between nutrients and frailty was strongest for beta-carotene,
      lutein/zeaxanthin, and total carotenoids (odds ratio ranging from 1.82 to 2.45, p
      =.05), after adjusting for age, sociodemographic status, smoking status, and body
      mass index. CONCLUSION: Frail women are more likely to have relatively low serum
      carotenoid and micronutrient concentrations and are more likely to have multiple
      micronutrient deficiencies. Future longitudinal studies are needed to examine the
      relationships between micronutrient concentrations and frailty in older women.

PMID- 16799144
TI  - Eating behavior and weight change in healthy postmenopausal women: results of a 4
      year longitudinal study.
AB  - BACKGROUND: The association of psychological eating behavior constructs with
      overweight and obesity during early adult life and middle age has been documented
      in several studies. However, the association of eating behavior with unexplained
      weight change in old age is relatively unexplored. METHODS: Body weight, eating
      behavior (dietary restraint, disinhibition, and hunger as assessed by the Eating
      Inventory), reported dietary intake, and physical activity level were assessed at
      baseline in 36 nonobese postmenopausal women aged 61.3 +/- 3.1 years (mean +/-
      standard deviation). Measurements were repeated 4.4 +/- 0.9 years later, and
      changes in body weight were examined in relation to baseline and follow-up eating
      behavior scores, reported dietary intake, and physical activity level. RESULTS:
      Participants had no major changes in health or lifestyle characteristics over the
      study interval. Weight change ranged from -7.5 to +5.8 kg (mean -0.3 +/- 3.5 kg),
      and there were no significant changes in reported dietary intake. Mean hunger
      score (calculated as the mean of baseline and follow-up hunger score) predicted
      weight change per year over the study period (bivariate r = 0.386, p =.020), even
      in statistical models adjusted for mean dietary intake variables (partial r =
      0.658, p =.003). Restraint, disinhibition, and physical activity level did not
      predict weight change. CONCLUSIONS: Reported hunger assessed by the Eating
      Inventory was associated with unintentional weight change in healthy
      postmenopausal women. The Eating Inventory questionnaire may provide a clinically
      useful tool for identifying older individuals at risk of undesirable weight
      change, and particularly unintentional weight loss, a factor strongly associated
      with increased morbidity and premature death in this population.

PMID- 16799145
TI  - Association between serum beta-carotene levels and decline of cognitive function
      in high-functioning older persons with or without apolipoprotein E 4 alleles:
      MacArthur studies of successful aging.
AB  - BACKGROUND: Growing evidence from animal studies suggests an interaction between
      antioxidants and apolipoprotein E (APOE) alleles on cognitive functioning. We
      used data from a 7-year cohort study of high-functioning older persons to explore
      whether the associations between serum beta-carotene level and subsequent decline
      of cognitive function differed by APOE 4 genotype. METHODS: Baseline information
      on sociodemographic characteristics, serum beta-carotene level, inflammation
      markers, APOE genotype, and cognitive functioning measured by a 9-item Short
      Portable Mental Status Questionnaire (SPMSQ) was obtained in 455 survivors.
      Multivariable logistic regression analyses were used to examine the relation
      between high serum beta-carotene level and risk of SPMSQ score decline in
      participants with or without APOE 4 alleles, while adjusting for age, sex, race,
      baseline SPMSQ score, and other covariates. RESULTS: Nine (2%) study participants
      had homozygous and 97 (21%) had heterozygous APOE 4 alleles. Two hundred forty
      nine (55%) had decline of SPMSQ scores during the follow-up. The presence of an
      APOE 4 allele was associated with higher risk and larger magnitude of SPMSQ score
      decline. The adjusted odds ratio of high beta-carotene level for cognitive
      decline was 0.11 (95% confidence interval, 0.02-0.57) in participants with at
      least one APOE 4 allele and 0.89 (95% confidence interval, 0.54-1.47) among those
      who were APOE 4 negative. CONCLUSION: Among high-functioning older persons,
      antioxidants and beta-carotene in particular may offer protection from cognitive
      decline in persons with greater genetic susceptibility as evidenced by the
      presence of the APOE 4 allele.

PMID- 16799146
TI  - Enteral feeding in end-stage dementia: a comparison of religious, ethnic, and
      national differences in Canada and Israel.
AB  - BACKGROUND: Although enteral feeding in end-stage dementia is thought by many
      clinicians to be "futile," it is still widely used. We examined rates of tube
      feeding (gastrostomy or nasogastric) in end-stage dementia in hospitals in both
      Canada and Israel, and hypothesized that Canadian non-Jewish affiliated hospitals
      would have the lowest (and Israeli institutions the highest), with Canadian
      Jewish hospitals exhibiting intermediate rates. METHODS: We conducted a cross
      sectional survey of six geriatric long-term hospitals: two in Israel and four in
      Canada (two Jewish affiliated, two not; two in Ontario, two in Quebec province).
      Patients with end-stage dementia were assessed and further analyzed for type of
      feeding. RESULTS: In the six hospitals, 2287 long-term beds were surveyed, of
      which 1358 (59.4%) were used by demented patients of whom 376 (27.7%) were
      severely demented (Global Deterioration Scale-level 7). Of these, 24.5% (92) were
      fed by nasogastric tube or gastrostomy tube. Significant differences in tube
      feeding prevalence were found between Canada (11%) and Israel (52.9%), with only
      4.7% seen in non-Jewish Canadian institutions. Jewish affiliated hospitals in
      Canada exhibited an intermediate rate of 19.6%. However, for within-country
      dyads, wide differences were also found. When we examined patient religion, we
      found that Canadian non-Jewish patients had the lowest rates (3.2%), Israeli
      Jewish patients the highest (51.7%), and Canadian Jewish patients exhibited an
      intermediate rate (19.0%) of tube use. CONCLUSIONS: Despite reservations
      concerning its utility, feeding tube use is reasonably widespread in patients who
      have reached the stage of severe dementia. Canadian institutions exhibited a
      lower prevalence of feeding tube use than did Israeli hospitals. Between-country
      and between-province differences in practice may be explained by some combination
      of administrative and/or financial incentives, religion, and culture; within
      country and within-ethnic group differences may be caused, at least in part, by
      differing institutional cultures.

PMID- 16799147
TI  - High cognitive dietary restraint is associated with increased cortisol excretion
      in postmenopausal women.
AB  - BACKGROUND: Cognitive dietary restraint (perceived ongoing effort to limit
      dietary intake to manage body weight) is common in women at all life stages. In
      young women, high dietary restraint has been associated with both increased
      excretion of cortisol (a stress hormone) and reduced bone mass. Whether this
      occurs in older women is unknown and is reported here for the first time.
      METHODS: Postmenopausal women (49-75 years old) with high (n = 41) or low (n =
      37) dietary restraint were compared to examine differences in urinary cortisol
      excretion, body composition assessed by dual-energy x-ray absorptiometry (bone
      mineral density, % body fat), dietary intake, anthropometrics, current exercise,
      and perceived stress. RESULTS: Women with high or low dietary restraint did not
      differ in age, body mass index, waist-to-hip ratio, energy intake, perceived
      stress, current exercise, or measures of body composition. However, urinary
      cortisol excretion was higher in the high restraint group (248.2 +/- 61.7 nmol/d
      vs 204.3 +/- 66.1 nmol/d; p =.01). Multiple regression analysis indicated that
      restraint group (high or low) independently predicted 7.6% of the variance in
      cortisol excretion. CONCLUSIONS: Postmenopausal women with high dietary restraint
      excrete more cortisol than do those with low restraint, suggesting that dietary
      restraint may be a source of stress. Although this was not associated with
      negative health effects in this sample, further investigation is warranted.

PMID- 16799148
TI  - Geriatric assessment in elderly heart failure patients.

PMID- 16799150
TI  - Designing amino acid residues with single-conformations.
AB  - Drug design can benefit from the use of non-coded amino acids, such as alpha
      amino isobutyric acids (Aib) or sarcosine (N-methyl-glycine). Non-coded amino
      acids can confer resistance to enzymatic degradation and increase the
      conformational stability of the peptides. We have simulated the conformational
      effects of combining N-methylation, bulky groups on the Calpha atom and/or
      thioamides using the class II CFF91 force field and our thioamide force field
      parameters. Although single amino acid substitutions (e.g. Aib) can restrict the
      available conformations, they do not necessarily lead to unique conformers,
      however, we predict that some of the amino acids described in this report will
      fold to a single phi, psi conformation (e.g. N-methylated and thioamide
      penicillamine). Several other amino acid/thiopeptide combinations were designed,
      which are predicted to prefer only two conformations. Novel amino acids of this
      type should prove useful for designing peptides with defined conformations.

PMID- 16799151
TI  - Effect of mutations on the dimer stability and the pH optimum of the human foamy
      virus protease.
AB  - To explore the role of residues being close to the catalytic aspartates in the
      higher pH optimum and in the lower dimer stability of human foamy virus (HFV)
      protease (PR) in comparison with human immunodeficiency virus type 1 (HIV-1)
      protease, single (Q8R, H22L, S25T, T28D) and double (Q8R-T28D, H22L-T28D) mutants
      were created based on sequence alignments and on the molecular model of HFV PR.
      The wild-type and mutant enzymes were expressed in fusion with maltose binding
      protein in Escherichia coli and the fusion proteins were purified by affinity
      chromatography. Specificity constant of most mutants was lower, but the value of
      Q8R-T28D double mutant enzyme was higher than that of the wild-type HFV PR.
      Furthermore, urea denaturation at two pH values and pH optimum values showed an
      increased stability and pH optimum for most mutants. These results suggest that
      the mutated residues may not be responsible for the higher pH optimum of HFV PR,
      but they may contribute to the lower dimer stability as compared with that of HIV
      1 PR.

PMID- 16799152
TI  - Interview with Dr. Paul Guyre and Mr. Lehn Weaver regarding pivotal advance:
      activation of cell surface Toll-like receptors causes shedding of the hemoglobin
      scavenger receptor CD163. Interview by Helene F. Rosenberg.

PMID- 16799153
TI  - Pivotal advance: activation of cell surface Toll-like receptors causes shedding
      of the hemoglobin scavenger receptor CD163.
AB  - The hemoglobin scavenger receptor (HbSR) CD163 is a monocyte/macrophage-specific
      glycoprotein that binds and facilitates uptake of haptoglobin-hemoglobin (Hp-Hb)
      complexes, which are rapidly formed in the circulation upon hemolysis of red
      blood cells. Hemolysis can be caused by a diverse range of infectious agents and
      provides pathogens a source of iron to enhance their survival and replication.
      Previous work demonstrated that lipopolysaccharide (LPS) activates monocytes to
      cleave cell-bound HbSR into a soluble mediator that retains the capacity to bind
      Hp-Hb complexes. We report that blocking LPS activation of Toll-like receptor 4
      prevents LPS-mediated shedding of CD163. Furthermore, activation of two other
      cell surface Toll-like receptors (TLR), TLR2 and TLR5, induces shedding of the
      HbSR from human monocytes. In contrast, treatment of monocytes with intracellular
      TLR3, TLR7, and TLR9 agonists failed to cause HbSR shedding, suggesting that this
      shedding event is selective to cell surface TLR activation. These data
      demonstrate that the soluble HbSR is released from monocytic cells in response to
      TLR signaling as an acute innate immune response to extracellular pathogen
      infections.

PMID- 16799155
TI  - The transcriptional ETS2 repressor factor associates with active and inactive
      Erks through distinct FXF motifs.
AB  - The transcriptional ETS2 repressor factor (ERF) is phosphorylated by Erks both in
      vivo and in vitro. This phosphorylation determines the subcellular localization
      and biological function of ERF. Here, we show that active and inactive Erk2
      proteins bind ERF with high affinity through a hydrophobic pocket formed by the
      alphaF and alphaG helices and the activation loop of Erk2. We have identified two
      FXF motifs on ERF that mediate the specific interaction with Erks. One of these
      motifs is utilized only by active Erks, whereas the other mediates the
      association with inactive Erks but also contributes to interaction with active
      Erks. Mutation of the phenylalanines of these motifs to alanines resulted in
      decreased association and phosphorylation of ERF by Erks both in cells and in
      vitro. ERF proteins carrying these mutations exhibited increased nuclear
      accumulation and increased inhibition of cellular proliferation. Expression of
      ERF regions harboring these motifs could inhibit Erk activity in cells. Our data
      suggest that, in the proper context, FXF motifs can mediate a strong and specific
      interaction not only with active but also inactive Erks and that these
      interactions determine protein function in vivo.

PMID- 16799156
TI  - Size matters for the tripeptidylpeptidase II complex from Drosophila: The 6-MDa
      spindle form stabilizes the activated state.
AB  - Tripeptidylpeptidase II (TPP II) is an exopeptidase of the subtilisin type of
      serine proteases, a key component of the protein degradation cascade in many
      eukaryotes, which cleaves tripeptides from the N terminus of proteasome-released
      products. The Drosophila TPP II is a large homooligomeric complex (approximately
      6 MDa) that is organized in a unique repetitive structure with two strands each
      composed of ten stacked homodimers; two strands intertwine to form a spindle
      shaped structure. We report a novel procedure of preparing an active,
      structurally homogeneous TPP II holo-complex overexpressed in Escherichia coli.
      Assembly studies revealed that the specific activity of TPP II increases with
      oligomer size, which in turn is strongly concentration-dependent. At a TPP II
      concentration such as prevailing in Drosophila, equilibration of size and
      activity proceeds on a time scale of hours and leads to spindle formation at a
      TPP II concentration of > or =0.03 mg/ml. Before equilibrium is reached,
      activation lags behind assembly, suggesting that activation occurs in a two-step
      process consisting of (i) assembly and (ii) a subsequent conformational change
      leading to a switch from basal to full activity. We propose a model consistent
      with the hyperbolic increase of activity with oligomer size. Spindle formation by
      strand pairing causes both significant thermodynamic and kinetic stabilization.
      The strands inherently heterogeneous in length are thus locked into a discrete
      oligomeric state. Our data indicate that the unique spindle form of the holo
      complex represents an assembly motif stabilizing a highly active state.

PMID- 16799157
TI  - Stepwise two-photon excited fluorescence from higher excited states of
      chlorophylls in photosynthetic antenna complexes.
AB  - Stepwise two-photon excited fluorescence (TPEF) spectra of the photosynthetic
      antenna complexes PCP, CP47, CP29, and light-harvesting complex II (LHC II) were
      measured. TPEF emitted from higher excited states of chlorophyll (Chl) a and b
      was elicited via consecutive absorption of two photons in the Chl a/b Qy range
      induced by tunable 100-fs laser pulses. Global analyses of the TPEF line shapes
      with a model function for monomeric Chl a in a proteinaceous environment allow
      distinction between contributions from monomeric Chls a and b, strongly
      excitonically coupled Chls a, and Chl a/b heterodimers/-oligomers. The analyses
      indicate that the longest wavelength-absorbing Chl species in the Qy region of
      LHC II is a Chl a homodimer with additional contributions from adjacent Chl b.
      Likewise, in CP47 a spectral form at approximately 680 nm (that is, however, not
      the red-most species) is also due to strongly coupled Chls a. In contrast to LHC
      II, the red-most Chl subband of CP29 is due to a monomeric Chl a. The two Chls b
      in CP29 exhibit marked differences: a Chl b absorbing at approximately 650 nm is
      not excitonically coupled to other Chls. Based on this finding, the refractive
      index of its microenvironment can be determined to be 1.48. The second Chl b in
      CP29 (absorbing at approximately 640 nm) is strongly coupled to Chl a.
      Implications of the findings with respect to excitation energy transfer pathways
      and rates are discussed. Moreover, the results will be related to most recent
      structural analyses.

PMID- 16799158
TI  - Assessment of personal direct-reading dust monitors for the measurement of
      airborne inhalable dust.
AB  - The performances of five portable direct-reading dust monitors were investigated
      in a wind tunnel for a range of industrial dusts and three sizes of aluminium
      oxide test dust to mainly determine their suitability for measuring the inhalable
      fraction of airborne dust in workplaces. The instruments tested were Split 2 (SKC
      Ltd), Sidepak (TSI Inc.), Dataram (Thermo Electron Ltd), PDS-2 (Sibata Scientific
      Technology Ltd) and the Respicon TM (Hund Ltd). The instruments' responses were
      compared with reference dust samplers. These were the IOM sampler for the
      inhalable fraction and the Casella cyclone sampler for the respirable fraction.
      All instruments are predominantly responsive to and are designed to measure
      particles in the respirable size range, although two of the instruments, the
      Split 2 and Respicon TM, are claimed to be capable of measuring inhalable-sized
      particles. For the purpose of the tests, major modifications to an existing wind
      tunnel dust injection system were made to facilitate the generation of uniform
      concentrations of large inhalable-sized dust particles at low air velocities.
      Each monitor greatly underestimated the measurement of inhalable concentration
      for all the dusts tested, although the linearity was good over a wide range of
      concentrations for any particular size distribution of dust. However, their
      calibration factors, defined as the ratio of reference inhalable concentration to
      monitor concentration, were especially sensitive to changes in particle size as
      the response of the instruments decreased rapidly with increasing particle size.
      The monitors generally overestimated the measurement of respirable dust
      concentration by up to a factor of about 2, apart from the PDS-2, which
      underestimated it by a factor of up to 3. There was, however, a great deal more
      scatter in the reference respirable concentration measurements owing to the
      collection of small dust samples. Therefore, monitor linearity and effects of
      monitor response to changes in particle size could not be accurately investigated
      for the respirable fraction. The sampling head of the Split 2 monitor
      incorporates an IOM inlet and filter to gravimetrically collect the inhalable
      fraction of airborne dust. This can give a concurrent reference measure of
      inhalable airborne dust concentration. However, poor sealing within the sampling
      head resulted in some of the sampled dust not reaching the backup filter. This
      resulted in the Split 2 underestimating the reference inhalable dust
      concentration, which meant that it could not be accurately used as a calibration
      standard. Communications with the manufacturers have since revealed that the
      sampling head has recently been redesigned in order to improve the seal and
      eliminate leakage. The Respicon sampler gravimetrically underestimated the
      inhalable dust concentration, and did so increasingly as the particle size
      increased.

PMID- 16799159
TI  - Assessment of occupational genotoxic risk in the production of rubber tyres.
AB  - A broad spectrum of substances is used in the rubber industry, many of them being
      genotoxic and/or carcinogenic. Convincing evidence of an excess of certain forms
      of cancer among rubber workers has been provided. The objective of this study was
      to determine the genotoxic effects in a group of individuals engaged in the
      production of rubber tyres from a Portuguese factory. Peripheral blood samples
      were collected from 32 exposed workers and 32 controls, and micronucleus (MN)
      test, sister chromatid exchanges (SCE) and comet assay were performed. Urinary
      thioethers were measured as a general biomarker of exposure to electrophilic
      compounds, and genetic polymorphisms in metabolizing enzymes (CYP2E1 Dra I, EPHX1
      codons 113 and 139, GSTP1 codon 105, and GSTM1 and GSTT1 deletion polymorphisms)
      were analysed as susceptibility biomarkers. Excretion of thioethers was found
      significantly higher in rubber workers. Also, a non-significant increase in MN
      frequency related to time of exposure and no effect in SCE were observed in the
      exposed. Comet assay data showed decreased TL values in the exposed population
      with respect to the control group, this might indicate the induction of
      crosslinks by the substances present in the workplace environment. Significant
      increase in MN frequency was obtained for GSTT1 null exposed individuals with
      respect to positive ones, and interaction with GSTP1 polymorphism was found.
      Higher levels of cytogenetic test frequencies were observed in epoxide hydrolase
      expected low activity donors with respect to medium and high activity
      individuals. No effect of CYP2E1 or GSTM1 variants was obtained in the biomarkers
      analysed.

PMID- 16799160
TI  - Intracellular killing of Brucella melitensis in human macrophages with
      microsphere-encapsulated gentamicin.
AB  - OBJECTIVES: Treatment of human brucellosis demands antibiotic targeting into the
      mononuclear-phagocytic system. The aim of this work was to prepare and
      characterize particulate carriers containing gentamicin and to study their
      interactions with phagocytic cells and bactericidal activity against
      intracellular Brucella melitensis. METHODS: Different poly(lactide-co-glycolide)
      (PLGA) polymers with free carboxylic end-group were used to formulate micro- and
      nanoparticles containing gentamicin, by a water-oil-water solvent-evaporation
      technique. PLGA 502H and 75:25H microparticles were selected because they showed
      the highest gentamicin loadings as well as good physico-chemical properties and
      sustained release in vitro. RESULTS: Gentamicin-containing microspheres of both
      polymers were successfully phagocytosed by infected THP-1 human monocytes, and
      immunocytochemistry studies revealed that the antibiotic reached Brucella
      specific compartments. A dose of 30 microg of encapsulated gentamicin was able to
      reduce intracellular Brucella infection by 2.2 log. CONCLUSIONS: Altogether,
      these results suggest that 502H and 75:25H microspheres are suitable carriers for
      gentamicin targeting inside human macrophages and thus for brucellosis treatment.

PMID- 16799162
TI  - Role of the subunit composition of central nicotinic acetylcholine receptors for
      the stimulatory and dopamine-enhancing effects of ethanol.
AB  - AIMS: The stimulatory, rewarding, and dopamine (DA)-enhancing effects of ethanol
      may involve central nicotinic acetylcholine receptors (nAChR), especially those
      located in the ventral tegmental area (VTA). Identifying the subunit composition
      that mediates these effects of ethanol would increase the understanding of the
      neurochemical basis underlying the addictive properties of ethanol. In the
      present series of experiments, the role of the alpha(3)beta(2)(*) and/or
      beta(3)(*) and/or alpha(6)(*) subunits of the nAChR for the stimulatory and DA
      enhancing effects of ethanol was investigated by using alpha-conotoxin MII
      (alphaCtxMII), selective to the alpha(3)beta(2)(*) and/or beta(3)(*) and/or the
      alpha(6)(*) subunits of the nAChR, and the alpha-conotoxin PIA-analogue
      (alphaCtxPIA-analogue), suggested to be selective to the alpha(6)(*) subunits.
      METHODS: alphaCtxMII and the alphaCtxPIA-analogue were synthesized using a
      modified literature procedure. The purity and identity of the peptides were
      confirmed with HPLC and FAB-MS analyses, respectively. Locomotor activity and in
      vivo microdialysis in freely moving mice were used. RESULTS: alphaCtxMII and the
      alphaCtxPIA-analogue were synthesized in good yields (>95%; >90%). In addition,
      we found that synthesized alphaCtxMII antagonized ethanol-induced locomotor
      stimulation, which confirms our previous results with the commercially available
      alphaCtxMII. Furthermore, the synthesized alphaCtxPIA-analogue, assumably also
      selective for alpha(6)(*) subunits of the nAChR, did neither antagonize the
      stimulatory nor the accumbal DA-enhancing effects of ethanol. CONCLUSION: These
      results indicate that alphaCtxMII- but not alphaCtxPIA-analogue-sensitive
      receptors, i.e. the alpha(3)beta(2)(*) and/or beta(3)(*) rather than the
      alpha(6)(*) subunits of the nAChR, appear to be of greater importance for these
      effects of ethanol and that these subunits could constitute neurochemical targets
      for developing new drugs for the treatment of alcohol dependence.

PMID- 16799163
TI  - 'I drink spirits to get drunk and block out my problems...' beverage preference,
      drinking motives and alcohol use in adolescence.
AB  - AIMS: To investigate among adolescents whether (i) drinking motives are related
      to beverage preference; (ii) beverage preference is related to alcohol use
      (drinking levels and risky drinking occasions); (iii) the association between
      beverage preference and alcohol use is moderated or mediated by drinking motives.
      METHOD: Data from a national representative sample of 5379 8th-10th graders in
      Switzerland (mean age 15.1, SD = 0.95) were analysed using multiple regression
      analyses. Beverage preference was based on the proportion of a specific beverage
      in the total amount of drinks consumed at the last drinking occasion. Drinking
      motives were assessed by the drinking motive questionnaire revised (DMQ-R).
      RESULTS: A significant positive association was found between enhancement motives
      and a preference for beer and spirits; the association was negative with regard
      to a preference for wine and alcopops. Conformity motives were positively related
      to a wine preference but negatively to a beer preference. Only a preference for
      beer and spirits was significantly associated with alcohol use in models that
      exclude motives. However, the association between beer preference and adolescent
      alcohol use was mediated by drinking motives. A preference for alcopops and
      spirits was moderated by motives: social drinkers who preferred alcopops drank
      less than those who did not prefer alcopops. Coping drinkers who preferred
      spirits drank more than those who preferred other alcoholic drinks. CONCLUSIONS:
      Drinking motives are potential explanatory factors for the association between
      beverage preference and alcohol use. Prevention approaches should target coping
      motives, particularly for adolescents who show a preference for spirits.

PMID- 16799164
TI  - Comparison of the combined marker GGT-CDT and the conventional laboratory markers
      of alcohol abuse in heavy drinkers, moderate drinkers and abstainers.
AB  - AIMS: A combined index based on gamma-glutamyltransferase (GGT) and carbohydrate
      deficient transferrin (CDT) measurements (GGT-CDT) has been recently suggested to
      improve the detection of excessive ethanol consumption. The aim of this work was
      to compare GGT-CDT with the conventional markers of alcohol abuse in individuals
      with a wide variety of alcohol consumption. METHODS: A cross-sectional and follow
      up analysis was conducted in a sample of 165 heavy drinkers, consuming 40-540 g
      of ethanol per day, and 86 reference individuals who were either moderate
      drinkers (n = 51) or abstainers (n = 35). RESULTS: GGT-CDT (5.35 +/- 1.08) in the
      heavy drinkers was significantly higher than in the reference individuals (3.30
      +/- 0.37). The sensitivity of GGT-CDT (90%) in correctly classifying heavy
      drinkers exceeded that of CDT (63%), GGT (58%), mean corpuscular volume (MCV)
      (45%), aspartate aminotransferase (AST) (47%), and alanine aminotransferase (ALT)
      (50%), being also essentially similar for alcoholics with (93%) or without (88%)
      liver disease. When comparing the data using either moderate drinkers or
      abstainers as reference population, the sensitivity of GGT-CDT, CDT, and ALT
      remained unchanged whereas the sensitivity of GGT, MCV, and AST was found to show
      variation. CONCLUSIONS: GGT-CDT improves the sensitivity of detecting excessive
      ethanol consumption as compared with the traditional markers of ethanol
      consumption. These findings should be considered in the assessment of patients
      with alcohol use disorders.

PMID- 16799165
TI  - Case finding for hepatitis C in primary care: a cost utility analysis.
AB  - BACKGROUND: Hepatitis C is an important public health problem. The need for more
      intensified action to identify those infected with the virus has been recognized.
      Primary care is an important setting for case finding. OBJECTIVES: To estimate
      the cost utility of case finding for hepatitis C in primary care, specifically
      amongst former injecting drug users (IDUs). METHODS: A Markov model was developed
      to investigate the impact of case finding and treatment on progression of
      hepatitis C (HCV) in a hypothetical cohort of 1000 former IDUs. Comparison was
      made with a similar cohort in which no systematic case finding was implemented
      but spontaneous presentation for testing was allowed. Two scenarios were
      explored. The testing protocol utilized ELISA and PCR tests. Those eligible for
      treatment received combination therapy with pegylated interferon and ribavirin.
      Parameter estimates were obtained from literature searches and experts in the
      field. RESULTS: Few estimates of the uptake of HCV testing in primary care are
      available. Cost utility was estimated at around 16,000 pounds sterling/QALY for
      both scenarios. At a willingness to pay of 30,000 pounds sterling/QALY, there is
      approximately a 75% probability that the initiatives would be cost-effective.
      Choices regarding the utility data, discounting and the rates of spontaneous/re
      presentation outside of a case-finding programme appear to be important areas of
      uncertainty in this model. CONCLUSION: Case finding for HCV in primary care is
      likely to be considered cost-effective but substantial uncertainties remain.
      Further research is needed on different approaches to case finding in primary
      care.

PMID- 16799166
TI  - Regular health care use by lesbians: a path analysis of predictive factors.
AB  - BACKGROUND: Lesbians have more health risks than other women but access
      preventive medical care less frequently. OBJECTIVE: To test the influence of (i)
      provider inquiry about sexual orientation, (ii) perceived provider gay-positivity
      and (iii) patient disclosure of sexual orientation on regular health care use in
      a sample of Canadian lesbians. METHODS: A path analysis using community survey
      data from 489 lesbian respondents. RESULTS: 78.5% [95% confidence interval (CI):
      74.7-82.0] of women reported regular health service use; 75.8% (95% CI: 72.2
      79.8) of women had disclosed their sexual orientation to their provider; and
      24.4% (95% CI: 20.6-28.2) of women had been asked about their sexual orientation
      by their provider. Of those women whose physicians had inquired about their
      sexual orientation, 100% (95% CI: 97.5-100.0) had disclosed. In the final path
      analysis, perceived provider gay-positivity and level of patient outness
      predicted disclosure, which, along with health status predicted regular health
      care use. All paths were significant at P < 0.05. CONCLUSIONS: Provider-related
      factors including perceived gay-positivity and inquiry about sexual orientation
      are strongly associated with disclosure of sexual orientation. Disclosure is
      associated with regular health care use. Minor changes to practice could improve
      access to health services for lesbians.

PMID- 16799167
TI  - Glycolipids from the red alga Chondria armata (Kutz.) Okamura.
AB  - Three distinct fractions containing polar glycolipids (PF(1-3)) were isolated
      from the chloroform soluble fraction of crude methanolic extract of red alga
      Chondria armata (Kutz.) Okamura on gel chromatography over Sephadex LH20. Their
      structure was elucidated by multidimensional nuclear magnetic resonance (NMR)
      techniques like 1H, 1H correlation spectroscopy (COSY), 1H, 1H total COSY
      (TOCSY), 1H, 13C heteronuclear multiple quantum coherence (HMQC), and 1H, 13C
      heteronuclear multiple bond correlation (HMBC) complemented by electrospray
      ionization mass spectrometry (ESI-MS) in the positive ion mode. The coupling
      constant of the anomeric proton in 1H NMR spectrum and sign of rotation indicated
      an exclusive configuration of the sugar molecules in the glycerolipids. Major
      glycolipids were identified as (2R)-2-O-(5,8,11,14-eicosatetranoyl)-3-O-alpha-d
      galactopyranosyl-sn-glycerol (GL2), its pentacetate (GL1), and (2R)-1-O
      (palmitoyl)-2-O-(5,8,11, 14,17-eicosapentanoyl)-3-O-beta-d-galactopyranosyl-sn
      glycerol (GL3). Each was methanolysed to give the same galactosylglycerol which
      on ESI-MS provided a pseudomolecular ion at m/z 309 representing deacylated
      glycolipid with the sodiated sugar moiety. Additionally, six minor glycolipids
      were also identified on the basis of ESI-MS. These include a 1,2-di-O-acyl-3-O
      (acyl-6'-galactosyl)-glycerol (GL1a), sulfonoglycolipids 2-O-palmitoyl-3-O-(6'
      sulfoquinovopyranosyl)-glycerol (GL2a) and its ethyl ether derivative (GL2b), 1
      oleoyl-2-palmitoyl-3-O-galactosyl glycerol (GL3a), and 1,2-diacyl phosphatidyl
      glycerol (GL3b). GL1, GL1a, and GL2b are new to the literature. The novelty of
      the remaining identified compounds lies in the diversity of their fatty acid
      composition. Antimicrobial properties of these glycolipids against pathogens were
      evaluated. The yeast Candida albicans and the bacteria Klebsiella sp. were as
      sensitive as the standard Nystatin and antibiotic Streptomycin against PF3.
      Considerable activity was expressed by the same metabolite against the fungus
      Cryptococcus neoformans as compared to the control. Weak activity against the
      bacteria Shigella flexineri and Vibrio cholerae and the fungus Aspergillus
      fumigatus was also observed. Fraction PF2 was weakly active against some strains
      whereas all of them were resistant to its acetyl derivative PF1. Antimicrobial
      activity of glycolipids is being reported here for the first time.

PMID- 16799168
TI  - Enamel-renal syndrome associated with hypokalaemic metabolic alkalosis and
      impaired renal concentration: a novel syndrome?

PMID- 16799169
TI  - The pharmacokinetics and tolerability of oseltamivir suspension in patients on
      haemodialysis and continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: Oseltamivir dose reduction is recommended for patients with end-stage
      renal disease (ESRD). However, dosing recommendations are not available for
      treatment or prophylaxis of influenza in these patients. This study assessed the
      pharmacokinetics and tolerability of oseltamivir in ESRD patients undergoing
      maintenance haemodialysis (HD) and continuous ambulatory peritoneal dialysis
      (CAPD). METHODS: In this open-label, multiple-dose study, patients received 30 mg
      oral oseltamivir suspension over 6.5 weeks. This dose was predicted to be
      suitable for ESRD patients based on a 2-compartment model. HD patients received 9
      doses given 1 h after the completion of alternate HD sessions (three times a
      week). CAPD patients received 6 doses given once weekly after a dialysate
      exchange. The primary parameters were peak plasma concentration (C(max)) and the
      area under the curve (AUC) for oseltamivir and oseltamivir carboxylate. RESULTS:
      In HD patients, the C(max) for oseltamivir carboxylate after single and repeated
      dosing were 943 and 1120 ng/ml, respectively. The mean AUC(0-42) was 31 600 ng
      h/ml for days 1-5 and 38 200 ng h/ml for days 38-43. Similarly, in CAPD patients,
      mean C(max) after the first and sixth doses were 885 and 849 ng/ml, respectively.
      The mean AUC(0-48) values for days 1-6 and days 36-43 were 33 400 and 32 400 ng
      h/ml, respectively. Oseltamivir was well-tolerated in both the patient groups.
      CONCLUSIONS: A 30 mg dose of oseltamivir given once weekly in CAPD or after
      alternate sessions in HD patients provides sufficient exposure to oseltamivir
      carboxylate to allow safe and effective anti-influenza treatment and prophylaxis.

PMID- 16799170
TI  - Defect in parathyroid-hormone-induced luminal calcium absorption in connecting
      tubules of Klotho mice.
AB  - BACKGROUND: Homozygous Klotho mutant mice (KL(-/-) mice) exhibit multiple
      phenotypes resembling human ageing. Increases in the ratio of urinary calcium to
      urinary creatinine (uCa/uCr) and in serum Ca concentration and decreases in
      urinary Cr excretion and serum parathyroid hormone (PTH) concentration were
      reported; however, precise information about renal Ca handling was not reported
      in these animals. METHODS: We evaluated the PTH-induced increase in intracellular
      Ca(2+) concentration ([Ca(2+)]i) in cells of isolated perfused connecting tubules
      (CNTs) of KL(-/-) mice. We also determined fractional excretion of Ca from the
      urine and serum samples of the same animals (n = 7), and compared them with
      KL(+/+) mice and hemi-nephrectomized KL(-+/+) mice (n = 10 in each) as controls.
      RESULTS: FECa was significantly higher in KL(-/-) mice than in controls (0.67 +/-
      0.13 vs 0.20 +/- 0.04%). The PTH (10 nM)-induced increase in [Ca(2+)]i was
      diminished in KL(-/-) mice (58 +/- 5 vs 231 +/- 15 nM). Addition of 10 nM of 8-(4
      chlorophenylthio)-cyclic adenosine 3',5'-monophosphate had a similar effect. The
      PTH-induced increase had completely disappeared by the removal of Ca from lumen
      and bath in both groups of animals. Removal of sodium (Na) from the solution
      increased [Ca(2+)]i to a similar extent in both groups. Conclusion. We conclude
      that renal Ca excretion estimated by determining FECa was defective in the KL(-/
      ) mice. Impairment of Ca absorption from the lumen by stimulation of PTH in CNTs
      is one of the mechanisms of this defect. Activity of the basolateral Na/Ca
      exchanger was preserved in this strain. Therefore, the pathway downstream after
      generation of second messengers following stimulation of PTH (such as the sorting
      of transporters of Ca absorption) might be impaired by disruption of the Klotho
      gene.

PMID- 16799171
TI  - RIFLE classification is predictive of short-term prognosis in critically ill
      patients with acute renal failure supported by extracorporeal membrane
      oxygenation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been utilized for
      critically ill patients, such as those with post-cardiotomy cardiogenic shock or
      life-threatening respiratory failure. Acute renal failure following ECMO support
      has an extremely elevated mortality rate. This study examined the outcomes of
      patients treated with ECMO and characterized the association between mortality
      and RIFLE (risk of renal failure, injury to the kidney, failure of kidney
      function, loss of kidney function and end-stage renal failure) classification.
      METHODS: This retrospective study analysed the medical records of 46 critically
      ill patients-most had post-cardiotomy cardiogenic shock-treated by ECMO. Sixteen
      patients (34.8%) were treated with both ECMO and continuous renal replacement
      therapies. RESULTS: The overall mortality rate was 65.2% (30/46). A progressive
      and significant increase (chi(2) for trend, P < 0.001) was observed for mortality
      based on RIFLE classification severity. The Hosmer and Lemeshow goodness-of-fit
      test demonstrated that the RIFLE category has a good fit. By applying the area
      under the receiver operating characteristic curve (AUROC), the RIFLE
      classification tool had good discriminative power (AUROC 0.868 +/- 0.068, P <
      0.001). Cumulative survival rates at 6 months follow-up following hospital
      discharge differed significantly (P < 0.05) for non-ARF vs RIFLE-I and RIFLE-F,
      and RIFLE-R vs RIFLE-F. CONCLUSION: This investigation confirms that the
      prognosis for critically ill patients supported by ECMO is grave. The RIFLE
      category is a simple, reproducible and easily applied evaluation tool with good
      prognostic capability that might generate objective information for patient
      families and physicians and supplements the clinical judgment of prognosis.

PMID- 16799172
TI  - Pharmacokinetics and dosage adjustment of oseltamivir and zanamivir in patients
      with renal failure.

PMID- 16799173
TI  - Mineral metabolism and cardiovascular morbidity and mortality risk: peritoneal
      dialysis patients compared with haemodialysis patients.
AB  - BACKGROUND: The K/DOQI guideline for bone metabolism and disease in chronic
      kidney disease is predominantly based on studies in haemodialysis (HD) patients.
      However, in clinical practice, this guideline is also applied to peritoneal
      dialysis (PD) patients. To validate the implementation of this guideline in PD
      patients, we evaluated the associations between plasma concentrations outside the
      K/DOQI-targets and the risk of cardiovascular morbidity and mortality in incident
      PD patients compared with HD patients. METHODS: In a large prospective
      multicentre study in the Netherlands (The Netherlands Cooperative Study on the
      Adequacy of Dialysis, NECOSAD), we included patients starting PD or HD between
      1997 and 2004. Relative risk of cardiovascular morbidity and mortality were
      estimated using time-dependent Cox regression modelling. RESULTS: We included 586
      PD patients with mean age 52 +/- 15 years (66% males) and 1043 HD patients with
      mean age 63 +/- 14 years (58% males). Cardiovascular disease (CVD) was the reason
      for hospitalization in 102 PD and 271 HD patients. In HD patients, the relative
      risk of CVD-related hospitalization increased with elevated plasma calcium
      concentrations (hazard ratio: 1.4; 95% CI: 1.1-1.9). Cardiovascular mortality was
      significantly higher for phosphorus concentrations above the K/DOQI-threshold in
      PD (2.4; 95% CI: 1.3-4.2) and HD patients (1.5; 95% CI: 1.1-2.1), and for
      elevated Ca x P in PD (2.2; 95% CI: 1.3-3.8) and HD patients (1.5; 95% CI: 1.1
      2.1). CONCLUSIONS: Plasma calcium concentrations above the K/DOQI-threshold
      increase the relative risk of CVD-related hospitalization in HD patients.
      Associations with cardiovascular mortality were more pronounced. Both in PD and
      HD patients with elevated plasma phosphorus and Ca x P concentrations, the
      cardiovascular mortality risk is increased. Therefore, it seems appropriate to
      adopt the current guideline in PD patients.

PMID- 16799174
TI  - Persistent hand motor commands in the amputees' brain.
AB  - The loss of a limb leads to sensorimotor modifications that are frequently
      accompanied by the vivid experience that the missing limb is still present, and
      that it can be moved at will. Furthermore, amputees can clearly distinguish
      between phantom movements of the fingers and of more proximal joints, like
      movements of the elbow. This phenomenon raises the question of whether these
      specific phantom movement experiences are translated into differentiated activity
      within the remaining muscles. We recorded stump muscle activity when above-elbow
      amputees voluntarily moved their phantom limb. Voluntary movements of the phantom
      hand triggered specific patterns of stump muscle activity, which differed from
      activity recorded in the same muscle groups during movements of the proximal
      limb. This result indicates that the brain's motor areas can be differentially
      activated according to the phantom movement the patient intends to perform, and
      suggests that hand motor commands are preserved after amputation. To further
      understand the interaction between central commands and sensory feedback in the
      perception of phantom movement we also measured stump muscle EMG activity in an
      amputee experiencing a frozen phantom limb, and in three below-elbow amputees
      with vivid phantom movements after inducing an ischaemic block. Failed attempts
      to move the paralysed phantom limb always resulted in the same EMG pattern, no
      matter what type of phantom movement was attempted, while ischaemic nerve block
      reduced or eliminated the ability to voluntarily move the phantom limb and
      produced a dramatic reduction in the amplitude of stump muscle EMG activity. Our
      data suggest that the experience of phantom hand movement involves the activation
      of hand motor commands. We propose that preserved hand movement representations
      re-target the stump muscles to express themselves and that when these
      representations are voluntarily accessible they can instruct the remaining
      muscles to move in such a way as if the limb is still there.

PMID- 16799175
TI  - Is pain the price of empathy? The perception of others' pain in patients with
      congenital insensitivity to pain.
AB  - Empathy is a complex form of psychological inference that enables us to
      understand the personal experience of another person through cognitive/evaluative
      and affective processes. Recent findings suggest that empathy for pain may
      involve a 'mirror-matching' simulation of the affective and sensory features of
      others' pain. Despite such evidence for a shared representation of self and other
      pain at the neural level, the possible influence of the observer's own
      sensitivity to pain upon his perception of others' pain has not been investigated
      yet. The aim of this study was to explore how patients with congenital
      insensitivity to pain (CIP), who are largely deprived of common stimulus-induced
      pain experiences, perceive the pain of others. Ratings of verbally presented
      imaginary painful situations showed that CIP patients' semantic knowledge
      regarding the pain of others did not differ from control subjects. Moreover, the
      propensity to infer pain from facial expressions was very similar between CIP
      patients and control subjects. On the other hand, when asked to rate pain
      inducing events seen in video clips in the absence of visible or audible pain
      related behaviour, CIP patients showed more variable and significantly lower pain
      ratings, as well as a reduction in aversive emotional responses, compared with
      control subjects. Interestingly, pain judgements, inferred either from facial
      pain expressions or from pain-inducing events, were strongly related to inter
      individual differences in emotional empathy among CIP patients, while such
      correlation between pain judgement and empathy was not found in control subjects.
      The results suggest that a normal personal experience of pain is not necessarily
      required for perceiving and feeling empathy for others' pain. In the absence of
      functional somatic resonance mechanisms shaped by previous pain experiences,
      others' pain might be greatly underestimated, however, especially when emotional
      cues are lacking, unless the observer is endowed with sufficient empathic
      abilities to fully acknowledge the suffering experience of others in spite of his
      own insensitivity.

PMID- 16799176
TI  - Prognostic indicators for non-recovery of non-traumatic complaints at arm, neck
      and shoulder in general practice--6 months follow-up.
AB  - OBJECTIVES: To identify predictors of non-recovery in non-traumatic complaints at
      the arm, neck and shoulder in general practice 6 months after the first
      consultation. METHODS: A prospective cohort study was set in 21 Dutch general
      practices. Consulters with a first or new episode of non-traumatic arm, neck or
      shoulder complaints and age 18 through 64 yrs entered the cohort. Complaint,
      patient, physical, psychosocial and work characteristics were investigated as
      possible predictors of non-recovery at 6 months using multiple logistic
      regression analyses (backward Wald). RESULTS: At 6 months, 46% of the total
      population (n = 612) and 42% of the working subpopulation (n = 473) still
      reported complaints. Complaint characteristics (long duration of the complaint
      before consultation, recurrent complaint, musculoskeletal comorbidity and
      complaint mainly located at wrist or hand) were most predictive of non-recovery
      followed by psychosocial characteristics (more somatization and experiencing less
      social support). Having a specific diagnosis was associated with recovery. In the
      working subpopulation, the same variables were predictors of non-recovery.
      Additionally, low supervisory support was associated with non-recovery. The
      models correctly classified 72-75% of the patients (explained variance 0.27
      0.28). CONCLUSIONS: Besides questions on complaint characteristics, information
      on somatization and support can help a general practitioner to recognize patients
      at risk of persistent complaints.

PMID- 16799177
TI  - Does gastro-oesophageal reflux following PEG placement in stroke patients predict
      a poorer outcome?

PMID- 16799179
TI  - Using dietetic assistants to improve the outcome of hip fracture.

PMID- 16799178
TI  - A case of hedonistic homeostatic dysregulation.
AB  - Parkinson's disease (PD) is a common condition especially amongst the elderly
      population, which is increasing. I present a case of an unusual but also under
      recognised syndrome caused by PD therapy, which can have devastating effects on
      the patient and their family.

PMID- 16799180
TI  - The impact of long-term warfarin on the quality of life of elderly people with
      atrial fibrillation.

PMID- 16799181
TI  - Characterization of the human patatin-like phospholipase family.
AB  - Several publications have described biological roles for human patatin-like
      phospholipases (PNPLAs) in the regulation of adipocyte differentiation. Here, we
      report on the characterization and expression profiling of 10 human PNPLAs. A
      variety of bioinformatics approaches were used to identify and characterize all
      PNPLAs encoded by the human genome. The genes described represent a divergent
      family, most with a highly conserved ortholog in several mammalian species. In
      silico characterization predicts that two of the genes function as integral
      membrane proteins and are regulated by cAMP/cGMP. A structurally guided protein
      alignment of the patatin-like domain identifies a number of conserved residues in
      all family members. Quantitative PCR was used to determine the expression profile
      of each family member. Affymetrix-based profiling of a human preadipocyte cell
      line identified several members that are differentially regulated during cell
      differentiation. Cumulative data suggest that patatin-like genes normally
      expressed at very low levels are induced in response to environmental signals.
      Given the observed conservation of the patatin fold and lipase motif in all human
      PNPLAs, a single nomenclature to describe the PNPLA family is proposed.

PMID- 16799182
TI  - An overview of dermatological conditions commonly associated with the obese
      patient.
AB  - Obesity is a chronic disease that may lead to skin problems, including acanthosis
      nigricans, skin tags, hyperandrogenism, striae distensae, plantar hyperkeratosis,
      and candidal intertrigo. Although some conditions (eg, skin tags and striae
      distensae) may simply be annoying or present cosmetic issues, conditions such as
      acanthosis nigricans and hyperandrogenism may be indicative of systemic diseases.
      Obesity also may contribute to poor healing of acute and chronic wounds that
      develop in this population. Some of the most common obesity-related skin
      disorders and factors affecting wound healing are described with suggestions on
      how to address these issues. With the continuing increase in the incidence of
      obesity, investigation into the specific care needs of this population is needed.
      In clinical practice, measures to reduce friction and shear and improve devices
      to move the obese patient would enhance care provision. Studies of the incidence
      of dermatological problems and the best treatments for these conditions are
      warranted.

PMID- 16799183
TI  - Bariatric surgery: patient incision care and discharge concerns.
AB  - Because it provides greater and more durable weight reduction than behavioral and
      pharmacological interventions for the morbidly obese, the number of bariatric
      surgeries is increasing - one such procedure is the Roux-en-Y gastric bypass. A
      cross-sectional study was conducted to examine incision care knowledge and
      discharge concerns of patients who had undergone this type of gastric bypass
      bariatric surgery. Participants (N = 31; 28 women, three men; mean age 45 years),
      recruited from a bariatric surgery center in a large, urban teaching hospital,
      had undergone a Roux-en-Y gastric bypass by either the open (n = 29) or
      laparoscopic (n = 2) method. Patients scheduled to be discharged home, 21 years
      of age or older, and able to understand and respond in English were eligible to
      participate. Participants completed questionnaires that included demographic
      information and rating scales regarding incision care knowledge, fears, and
      discharge concerns. Mean time from hospital admission to study participation was
      1.1 days (SD = 3 days). Knowledge of incision care and amount of information
      received about incision care were rated low. The five most frequently mentioned
      postdischarge concerns included bowel trouble at home, wound pain at home,
      looking for wound complications, watching for wound infection, and activity
      limitations. The higher the amount of information received about incision care,
      the higher the patient's knowledge (r = .57, P <.001). Lower incision care
      knowledge scores were correlated with a higher fear of incision care (r = .46, P
      = .008) and patients reporting greater pain had more concerns about discharge (r
      = .49, P <.005). Little is known about preparing the bariatric surgery patient
      for discharge home. To improve outcomes, research that examines issues including
      discharge teaching methods, patient concerns, and information for persons
      undergoing bariatric surgery is needed.

PMID- 16799184
TI  - A prospective, randomized, controlled trial of autologous platelet-rich plasma
      gel for the treatment of diabetic foot ulcers.
AB  - Nonhealing diabetic foot ulcers are a common cause of amputation. Emerging
      cellular therapies such as platelet-rich plasma gel provide ulcer management
      options to avoid loss of limb. The purpose of this prospective, randomized,
      controlled, blinded, multicenter clinical study was to evaluate the safety and
      efficacy of autologous platelet-rich plasma gel for the treatment of nonhealing
      diabetic foot ulcers. One hundred, twenty-nine (129) patients were screened; 72
      completed a 7-day screening period and met the study inclusion criteria. Patients
      were randomized into two groups - the standard care with platelet-rich plasma gel
      or control (saline gel) dressing group - and evaluated biweekly for 12 weeks or
      until healing. Healing was confirmed 1 week following closure and monitored for
      another 11 weeks. An independent audit led to the exclusion of 32 patients from
      the final per-protocol analysis because of protocol violations and failure to
      complete treatment. In this group, 13 out of 19 (68.4%) of the platelet-rich
      plasma gel and nine out of 21 (42.9%) of the control wounds healed. After
      adjusting for wound size outliers (n = 5), significantly more platelet-rich
      plasma gel (13 out of 16, 81.3%) than control gel (eight out of 19, 42.1%)
      treated wounds healed (P = 0.036, Fisher's exact test). Kaplan-Meier time-to
      healing also was significantly different between groups (log-rank, P = 0.0177).
      No treatment-related serious adverse events were reported and bovine thrombin
      used in the preparation of PRP did not cause Factor V inhibition. When used with
      good standards of care, the majority of nonhealing diabetic foot ulcers treated
      with autologous platelet-rich plasma gel can be expected to heal.

PMID- 16799185
TI  - Blood-brain barrier and cell-cell interactions: methods for establishing in vitro
      models of the blood-brain barrier and transport measurements.
AB  - This chapter describes in vitro methods for studying the blood-brain barrier.
      These methods include a cell line and isolated brain microvessels. The rat brain
      endothelial cell line 4 (RBE4) express many properties that are expressed by
      brain endothelial cells in vivo. Tissue culture methods allow the investigator to
      design experiments for studying transporters and permeability that would be much
      more difficult in vivo. A method for making preparations of isolated brain
      microvessels also is described. These preparations are highly enriched and also
      can be used for studying transport in vitro, but their short life span is a
      limitation. Two methods are discussed for measuring transport in cell culture. In
      one method, permeability is measured across a cell mono-layer. This method is
      useful for measuring luminal and abluminal transport. The second method is
      especially designed for measuring the families of efflux transporters. These in
      vitro methods will complement many of the in vivo techniques, and they may be
      used as screening for more timely and expensive experiments, and also reducing
      the need for experimental animals.

PMID- 16799186
TI  - Interactions of intestinal epithelial cells with bacteria and immune cells:
      methods to characterize microflora and functional consequences.
AB  - Epithelial cells at all mucosal surfaces are potentially apposed to bacteria,
      particularly in the intestine. It is established that intestinal epithelial cells
      (IECs) represent an important barrier between lamina propria cells and the
      potentially harmful lumenal contents. In addition, IECs are important
      immunoeffector cells with the capacity to release cytokines, chemokines, and
      other molecules involved in antigen presentation and immune defense. The
      interaction of IECs with intestinal bacteria can result in a decrease in barrier
      function and the development of inflammation, which is known to be an important
      factor in the development of intestinal pathology. The potential role of such
      crosstalk between bacteria and other intestinal cell types in normal physiology
      and/or pathophysiology is therefore a topic of intense investigation. In this
      chapter, we provide protocols for the identification of bacteria that are
      associated with the epithelium and mucosa in addition to functional assays
      examining the interactions of neutrophils with epithelial cells and epithelial
      cell-mediated killing of bacteria.

PMID- 16799187
TI  - The role of junctional adhesion molecules in interactions between vascular cells.
AB  - Adhesive interactions between cells regulate tissue integrity as well as the
      process of inflammatory cell recruitment. Such intercellular interactions are
      regulated by adhesion receptors and can be homotypic, that is, between cells of
      the same type, for example, between adjacent endothelial cells in the
      vasculature, as well as heterotypic, that is, between different cells, such as
      the leukocyte endothelial interactions that take place during leukocyte
      extravasation. Emerging evidence points to the importance of the family of
      junctional adhesion molecules (JAMs), which are localized in interendothelial
      contacts and are implicated in the regulation of leukocyte extravasation. JAMs
      are members of the immunoglobulin superfamily and can undergo both homophilic and
      heterophilic interactions. This chapter deals with the role of JAMs in the
      regulation of adhesive interactions between vascular cells.

PMID- 16799188
TI  - Cell-cell interactions on solid matrices.
AB  - Models to study molecular, biochemical, and functional responses in vitro
      generally incorporate an individual cell type or group of cells organized in a
      random fashion. Normal physiological responses in vivo require that individual
      cell types be oriented in an organized fashion with three-dimensional
      architecture and appropriately positioned cellular interfaces. Much recent
      progress has been made in the development and implementation of models to study
      cell-cell contact using substrate grown cells. Here, we summarize the use of
      membrane permeable supports to study functional responses in appropriately
      positioned cell types. These models incorporate two or more different cells
      cultured in physiologically positioned locales on solid substrates. Models
      incorporating nonadherent cells (e.g., leukocytes) in co-culture with such models
      also are discussed. Such models have been used extensively to discovery both cell
      bound as well as soluble mediators of physiological and pathophysiological
      processes.

PMID- 16799189
TI  - Cell-cell interactions in the kidney: inducible expression of mutant G protein
      alpha-subunits in Madin-Darby canine kidney cells for studies of epithelial cell
      junction structure and function.
AB  - Disrupted epithelial cell junctions are a hallmark of numerous disease processes.
      The signaling mechanisms regulating barrier function and re-establishment of
      intact junctions after injury and during development are complex and tightly
      regulated. We have shown that heterotrimeric G proteins regulate assembly and
      maintenance of epithelial cell barrier in cultured Madin-Darby canine kidney
      (MDCK) cells. The inducible expression of mutant signaling molecules
      (constitutively active or dominant negative) in polarized cells is a useful
      strategy for elucidating the role(s) for specific proteins. Using tetracycline
      off inducible expression of wild-type and constitutively active Galpha12, we have
      demonstrated a fundamental role for Galpha12 in regulating the junction of MDCK
      cells. Inducible expression permits the comparison of the identical cell line in
      the presence and absence of the protein of interest and minimizes variation
      arising from distinct clones. The methods described here are applicable to
      virtually any protein that may regulate maintenance or assembly of the epithelial
      cell junctional complex.

PMID- 16799190
TI  - Nucleotide metabolism and cell-cell interactions.
AB  - Interactions between the vascular endothelium and polymorphonuclear leukocytes
      (PMNs) are central to PMN emigration into inflamed tissues, and to neutrophil
      endothelial crosstalk pathways that modulate inflammatory responses and vascular
      barrier function. For example, during episodes of inflammation, the
      transendothelial migration (TEM) of PMNs potentially disturbs vascular barrier
      and gives rise to intravascular fluid extravasation and edema. However, because
      of the close special relationship between PMNs and the vascular endothelium, TEM
      creates an ideal situation for neutrophil-endothelial crosstalk. While
      investigating innate mechanisms to dampen intravascular fluid loss and edema
      occurring during TEM, we observed that PMNs release adenine nucleotides after
      activation (adenosine triphosphate [ATP] and adenosine monophosphate [AMP]). ATP
      and AMP are metabolized by endothelial cell-surface enzymes, the ecto-apyrase
      (CD39, metabolizes ATP to AMP) and the 5'-ecto-nucleotidase (CD73, metabolizes
      AMP to adenosine). Adenosine generated in this fashion can activate endothelial
      adenosine receptors, leading to increases in intracellular cyclic AMP and
      resealing of the endothelial junctions, thereby promoting vascular barrier
      function. This crosstalk pathway provides an endogenous mechanism to dampen
      vascular leak syndrome during neutrophil-endothelial interaction. In other words,
      during TEM, neutrophils close the door behind them.

PMID- 16799191
TI  - Analysis of Mammalian sperm-egg membrane interactions during in vitro
      fertilization.
AB  - The interactions between egg and sperm are among the most fascinating in cell
      biology. These interactions include cell-cell adhesion and then membrane fusion
      between the two gametes. This chapter details the experimental methods used to
      for gamete culture and in vitro fertilization using mouse sperm and eggs.

PMID- 16799192
TI  - Collagen gel contraction assay.
AB  - Mucosal tissues undergo contraction and relaxation on a continuous basis. In its
      normal state, the pliable intestinal tract is characterized by a rhythmic pattern
      of contractions controlled by its intrinsic neuronal innvervation. In chronic
      inflammatory diseases such as Crohn's disease, the intestine can become stiff and
      fibrotic, losing much of its normal motility. Although muscle fiber contraction
      accounts for much of this activity, contraction of nonmuscle tissue is constantly
      occurring in events associated with chronic inflammation, such as wound healing,
      scar formation, and tissue remodeling. However, the physiological and
      pathological mechanisms defining these events are not well defined. Tissue
      contraction is a dynamic event characterized by both intracellular and
      extracellular events. A number of cells, such as fibroblasts, epithelial cells,
      lymphocytes, and eosinophils, normally reside within the gastrointestinal tract.
      Additionally, the extracellular matrix is composed of a complex infrastructure
      that includes collagen and other molecules. The manner in which these two
      components interact is not certain, but the use of recent model systems has
      provided insights into these processes. The collagen lattice contraction assay
      provides a model for tissue contraction that takes advantage of the finding that
      cell-populated collagen hydrogels contract over time in a predictable, consistent
      manner. This model allows for investigation of the influence of specific agonists
      on the rate and extent of matrix contraction.

PMID- 16799193
TI  - Methods to assess tissue permeability.
AB  - An essential requirement for adequate organ performance is the formation of
      permeability barriers that separate and maintain compartments of distinctive
      structure. The endothelial cell lining of the vasculature defines a semipermeable
      barrier between the blood and the interstitial spaces of all organs. Disruption
      of the endothelial cell barrier can result in increased permeability and vascular
      leak. These effects are associated with multiple systemic disease states. The
      mechanisms that control barrier function are complex and their full understanding
      requires a multidisciplinary approach. In vivo permeability data often complement
      molecular findings and add power to the studies. The interaction of multiple cell
      types and tissues present only on mammalian models allow for testing of
      hypothesis and to establish the physiological significance of the results. In
      this chapter, we describe methods that can be used systematically to measure the
      permeability characteristics of several organs.

PMID- 16799195
TI  - A biochemical method for tracking cholera toxin transport from plasma membrane to
      Golgi and endoplasmic reticulum.
AB  - Asiatic cholera is a rapidly progressing disease resulting in extreme diarrhea
      and even death. The causative agent, cholera toxin, is an AB5-subunit enterotoxin
      produced by the bacterium Vibrio cholera. The toxin must enter the intestinal
      cell to cause disease. Entry is achieved by the B-subunit binding to a membrane
      lipid that carries the toxin all the way from the plasma membrane through the
      trans-Golgi to the endoplasmic reticulum (ER). Once in the ER, a portion of the A
      subunit, the A1 chain, unfolds and separates from the B-subunit to retro
      translocate to the cytosol. The A1 chain then activates adenylyl cyclase to cause
      disease. To study this pathway in intact cells, we used a mutant toxin with C
      terminal extension of the B-subunit that contains N-glycosylation and tyrosine
      sulfation motifs (CT-GS). This provides a biochemical readout for toxin entry
      into the trans Golgi (by 35S-sulfation) and ER (by N-glycosylation). In this
      chapter, we describe the methods we developed to study this trafficking pathway.

PMID- 16799194
TI  - Bacterial-bacterial cell interactions in biofilms: detection of polysaccharide
      intercellular adhesins by blotting and confocal microscopy.
AB  - Adhesive interactions between bacterial cells coupled with adherence to a solid
      surface can lead to the formation of a biofilm. The important role of biofilm
      formation in the pathogenesis of certain types of infection, especially those
      involving indwelling medical devices, is becoming increasingly apparent. Critical
      to the development of a biofilm is the elaboration of exo-polysaccharide that
      contributes to substrate and intercellular adhesion. The synthesis and secretion
      of large exo-polysaccharides is a metabolically expensive process and is
      therefore often suppressed under conditions that favor the planktonic mode of
      growth. One way to identify the environmental cues that cause a given bacterial
      species to switch to the biofilm mode of growth is to monitor exo-polysaccharide
      elaboration in vitro. The exo-polysaccharide involved in biofilm formation in a
      number of bacterial species is a polymer of N-acetyl-glucosamine. In this
      chapter, we outline two methods that use wheat germ agglutinin, a lectin that
      binds to N-acetyl-glucosamine, to evaluate extracellular polysaccharide
      production by a variety of bacterial species.

PMID- 16799196
TI  - Isolation and culture of murine heart and lung endothelial cells for in vitro
      model systems.
AB  - The inflammatory response is a critical component of host defense. An important
      goal of our group has been to understand the endothelial-dependent mechanisms
      that mediate leukocyte recruitment during an inflammatory response. In this
      chapter, we present a detailed method for the isolation and in vitro culture of
      murine vascular endothelial cells from the lung and heart. The endothelial cells
      are of high purity (85-99%) and retain certain of their functional differences,
      including constitutive and cytokine inducible adhesion molecule expression and
      chemokine production. Such endothelial cells, therefore, can be used for various
      in vitro models including leukocyte adhesion assay or in depth biochemical
      analyses.

PMID- 16799198
TI  - Assays for the calcium sensitivity of desmosomes.
AB  - Epithelial cells in vivo exist as confluent cell sheets, but this confluence is
      disrupted if the sheets are wounded, if the cells are undergoing morphogenesis,
      or if they are taking part in invasion and metastasis. Desmosomes are one of the
      principal types of adhesive junctions in epithelia and are responsible for
      maintaining tissue integrity. It is likely that modulation of desmosomal adhesion
      is required to facilitate cell motility in response to alterations in the tissue
      architecture. Desmosomal adhesion changes from a calcium-dependent state to a
      calcium-independent state when cells become confluent. Our laboratory has shown
      that the alpha isoform of protein kinase C is involved in signaling the response
      of desmosomes to calcium concentration and wounding, in cultured epithelial cells
      and in mouse epidermis (in vivo).

PMID- 16799197
TI  - Expression cloning of signaling proteins regulated by cell adhesion.
AB  - Many proteins involved in cell-cell and cell-matrix adhesion are regulated by
      signal transduction pathways and can activate signal transduction on ligation.
      Adhesion-related signal transduction is important throughout development,
      hemostasis, immunity, and in diseases such as cancer. Therefore, the
      identification of the various signaling pathways that are involved is crucial.
      Expression cloning is an unbiased way to isolate proteins with specific
      biological functions. This methodology has been adapted for the identification of
      proteins involved in cell signaling pathways that are mediated by cell-cell and
      cell-matrix interactions. We have successfully developed and used a novel
      expression cloning strategy to isolate the integrin-regulated apoptosis signaling
      protein BIT-1. This screen was based on previous observations that integrin
      mediated adhesion upregulates the anti-apoptotic protein bcl-2. Our strategy
      described in this chapter uses flow cytometry and a reporter construct in which
      the bcl-2 promoter is linked to enhanced green fluorescence protein. The
      advantage of using flow cytometry in expression cloning is that it increases the
      sensitivity of the screen by enabling us to examine function quantitatively at
      the level of a single cell millions of times in one experiment. The following
      protocol provides a detailed method for the isolation of proteins that are
      regulated by cell adhesion.

PMID- 16799199
TI  - Tight junctions and cell-cell interactions.
AB  - Chronic inflammation in mucosal tissues can influence epithelial barrier function
      via pro-inflammatory cytokines such as interferon (IFN)-gamma and tumor necrosis
      factor-alpha. Increased mucosal levels of these cytokines have been observed in
      mucosal biopsies from patients with a chronic inflammatory condition referred to
      as inflammatory bowel disease. Paracellular permeability across epithelial cells
      is regulated by tight junctions (TJs), which are the apical most junctions in
      epithelial cells. Given that pro-inflammatory cytokines modulate the epithelial
      barrier and that TJs regulate epithelial permeability, we analyzed the influence
      of IFN-gamma on U function/structure. Our results suggest that IFN-gamma induced
      a time-dependent increase in paracellular permeability that was associated with
      internalization of TJ transmembrane proteins, occludin, junction adhesion
      molecule A, and claudin-1. In this chapter, we focus on selected methods used to
      investigate the influence of IFN-gamma on epithelial barrier function.

PMID- 16799200
TI  - Simultaneous immunofluorescence detection of cadherin and beta-catenin in mouse
      tissue sections.
AB  - Both cell-cell adhesion and secreted signaling molecules are involved in the
      regulation of normal tissue development and maintenance. beta-catenin seems to
      link cadherin-mediated cell-cell adhesion and Wnt signaling. Thus, its activity
      in particular cells or tissues, either during normal development or in
      tumorigenesis, has become a fascinating topic of investigation. Because the
      multiple functions of beta-catenin intimately relate to its amount and
      localization within a cell, immunohistochemical detection of this molecule
      simultaneously with the cell adhesion molecule cadherin should provide helpful
      information on its potential activities. This detection can be conducted on
      tissue sections by using appropriate tissue preparation procedures and primary
      antibodies from different species.

PMID- 16799201
TI  - In vitro neutrophil transepithelial migration.
AB  - Polymorphonuclear leukocyte (PMN) transmigration into tissues is a highly
      regulated process and plays a central role in host defense. In inflammatory human
      diseases such as ulcerative colitis and Crohn's disease, the infiltration of
      intestinal mucosa by large numbers of PMNs contributes to epithelial
      pathophysiology. The sequence of events that fine-tune PMN migration across
      epithelial cells is not well-understood. In this chapter, we describe a method to
      study PMN transmigration across intestinal epithelial T84 monolayers using a
      modified Boyden chamber system. This in vitro model system consists of three main
      components: the epithelium, purified PMN, and a chemoattractant gradient.
      Intestinal epithelial cells are cultured as inverted monolayers on permeable
      filter supports to facilitate the study of PMN transmigration in the
      physiologically relevant basolateral-to-apical direction. PMNs are isolated from
      human blood using dextran sedimentation followed by Ficoll density gradient
      centrifugation. PMN transmigration is elicited using N-formyl-methionyl-leucyl
      phenylalanine gradients and is quantified by assaying for myeloperoxidase
      activity. The advantages of this model are its reductionist approach and the fact
      that the system can be easily manipulated. Studies using this model system will
      shed more light on the mechanisms regulating PMN responses in acute inflammatory
      diseases.

PMID- 16799202
TI  - The blot rolling assay: a method for identifying adhesion molecules mediating
      binding under shear conditions.
AB  - Adhesive interactions of cells with blood vessel walls under flow conditions are
      critical to a variety of processes, including hemostasis, leukocyte trafficking,
      tumor metastasis, and atherosclerosis. We have developed a new technique for the
      observation of binding interactions under shear, which we have termed the "blot
      rolling assay." In this method, molecules in a complex mixture are resolved by
      gel electrophoresis and transferred to a membrane. This membrane can be rendered
      semitransparent and incorporated into a parallel-plate flow chamber apparatus.
      Cells or particles bearing adhesion proteins of interest are then introduced into
      the chamber under controlled flow, and their interactions with individual
      components of the immobilized substrates can be visualized in real time. The
      substrate molecules can be identified by staining with specific antibodies or by
      excising the relevant band(s) and performing mass spectrometry or microsequencing
      of the isolated material. Thus, this method allows for the identification, within
      a complex mixture and without previous isolation or purification, of both known
      and novel adhesion molecules capable of binding under shear conditions.

PMID- 16799203
TI  - Cell-cell interaction in the transcellular biosynthesis of novel omega-3-derived
      lipid mediators.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA)
      and docosa-hexaenoic acid (DHA) display beneficial actions in human diseases. The
      molecular basis for these actions remains of interest. We recently identified
      novel mediators generated from omega-3 PUFA during cell-cell interactions that
      displayed potent anti-inflammatory and proresolving actions. Compounds derived
      from EPA are designated resolvins of the E series (RvE1), and those
      biosynthesized from DHA are denoted resolvins of the D series (RvD) and
      docosatriene, such as protectin D1 (PD1), which belongs to the family of
      protectins. In addition, treatment using aspirin initiates a related epimeric
      series by triggering endogenous formation of the 17R-RvD series, denoted as
      aspirin-triggered (AT)-RvDs. These compounds possess potent anti-inflammatory
      actions in vivo that essentially are equivalent to their counterpart generated
      without aspirin, namely the 17S-RvDs. In this chapter, we provide an overview and
      detail protocols of the biosynthesis and bioactions of these newly uncovered
      pathways and products that include three distinct series: 18R-resolvins of the E
      series derived from EPA (i.e., RvE1); 17R-resolvins of the D series from DHA (AT
      RvD1 through RvD4); and 17S-resolvins of the D series from DHA (RvD1 through
      RvD4).

PMID- 16799204
TI  - Isolation and analysis of lipid rafts in cell-cell interactions.
AB  - Lipid rafts are dynamic structures made up of proteins and lipids that float
      freely within the liquid-disordered bilayer of cellular membranes and have the
      ability to cluster to form larger, more-ordered platforms. These clustered
      structures have been identified in all cell types and have been shown to play
      critical roles in signal transduction, cellular transport, and cell-cell
      communication. Lipid rafts also have been implicated in facilitating
      bacterial/viral entry into host cells and in human disease, highlighting the
      significance of understanding the role lipid rafts play in physiological and
      pathological signaling outcomes. In this chapter, we provide protocols to isolate
      lipid rafts from polarized and nonpolarized cells and outline novel technologies
      to analyze signal transduction cascades in vivo.

PMID- 16799205
TI  - Asymptomatic diabetes: the difference between population-based and office-based
      screening.
AB  - AIM: To compare the results between population-based and office-based diabetes
      screening. METHODS: In 1997, a population-based screening was performed on a
      group of government employees and retired subjects in the Makassar Municipality.
      Since the year 2000, we performed screening at the clinic. For clinical-based
      screening, we focused the screening on those with high risks for developing
      diabetes mellitus, i.e. all subjects aged > or =45 or those aged < 45 with one or
      more of the following abnormalities: obese (BMI > 25 kg/m2), elevated blood
      pressure (> or =140/90 mmHg in adults), family history of diabetes, previous
      identified IFG or IGT, HDL-cholesterol < or =35 mg/dl and/or triglyceride > or
      =250 mg/dL, and history of gestational diabetes mellitus or delivery of babies >
      or =4000 gram. For population-based screening, the criteria for diabetes mellitus
      was based on a single test 2-hours post load (75 gram glucose), while for office
      based screening, the WHO l999 was used i.e. fasting and 2-hours post 75 gram
      glucose load (OGTT). RESULTS: During the screening in the population, 941
      subjects were screened, 290 women and 651 men. There were 51 diabetic subjects,
      or a prevalence of 5.42%, 21 women or 7.24% of all women, and 30 men or 4.60% of
      all men. At the clinical setting, 907 were screened, 483 women and 424 men. Among
      these subjects, 155 fulfilled the diabetes criteria, with a prevalence of 17.1%.
      There were 78 diabetic women or 16.1% of all women, and 77 men or 18.2% of all
      men. If the diagnosis of diabetes mellitus in the clinical setting is based only
      on 2 hours post load (the same as for population-based) only 70 patients can be
      detected, for a prevalence of 7.7%, which is still higher compared to the results
      of the population-based screening. All figures obtained from the office-based
      screening were higher as compared to the population-based results. CONCLUSION:
      These results show that office-based screening detected more asymptomatic
      diabetes compared to population-based screening. It is suggested that early
      detection of asymptomatic diabetes is performed at the clinic, either at the
      hospital or doctor's private office.

PMID- 16799206
TI  - Gene rearrangements in follicular lymphoma among Indonesian.
AB  - AIM: Gene rearrangement has an important role in the management of lymphoma. We
      investigated the rearrangements of B-cell leukaemia/lymphoma 2 (BCL2), BCL6 and
      Paired homeobox 5 (PAX5) genes in Indonesian follicular lymphoma (FL) patients.
      METHODS: We examined gene rearrangements using various kinds of polymerase chain
      reactions (PCRs) on 24 patients' peripheral blood DNA. RESULTS: BCL2
      rearrangement was found in 58% (14 of 24 patients), 8 at mbr (major breakpoint
      region), 2 at mcr (minor cluster region) and 4 at icr (intermediate cluster
      region), respectively. No rearrangement in BCL6 and PAX5 was detected. There was
      a significant difference in the incidence of spleen involvement between patients
      with BCL-2 rearrangement and without it (50% vs. 11%, p=0.04). BCL-2
      rearrangement was correlated with spleen involvement (OR=9) and anemia (OR=2.3).
      CONCLUSION: BCL2 rearrangement in Indonesian FL was higher than previous reports
      from other Asia countries (58% vs. 48%, respectively). Our method using
      peripheral blood DNA might be useful for the molecular diagnosis of FL.

PMID- 16799207
TI  - Epstein-barr nuclear antigen-1 (EBNA-1) in diffuse large B-cell lymphoma and its
      relationship to the bcl-2 protein.
AB  - AIM: To determine EBNA-1 expression in the tissue of patients with diffuse large
      B-cell lymphoma and its relationship to bcl-2 expression. METHODS: Paraffin
      embedded tissue from 24 cases of diffuse large B-cell lymphoma were stained
      immunohisto chemically with monoclonal antibody anti-EBNA-1 and anti-bcl-2 using
      Streptavidin Biotin Complex method. The bcl-2 expression was measured as negative
      (no staining), positive 1 (weak staining), and positive 2 (moderate to strong
      staining). The relationship between the immunohisto chemistry results was
      examined. RESULTS: From the 24 samples, 12 (50%) were EBNA-1 positive and 14
      (58.3%) showed expression of bcl-2. Eleven of the 14 samples (90%) showed
      expression of bcl-2 were EBNA-1 positive, while only 3 of these samples (10%)
      were EBNA-1 negative. The relationship between bcl-2 expression and EBNA-1 was
      statistically significant (Chi square-uncorrected 11.2571, p= 0.0036).
      CONCLUSION: Our results showed that 50% of diffuse large B-cell lymphoma were
      EBNA-1 positive. Furthermore, EBNA-1 seemed to be correlated with bcl-2
      expression.

PMID- 16799208
TI  - Left ventricular diastolic dysfunction in obese women.
AB  - AIM: To determine the direct effect of obesity on echocardiographic indices of
      diastolic left ventricular function METHODS: 44 obese (BMI > or =25 kg/m2) and 45
      normal weight women were studied. They had no other pathological conditions.
      Echocardiographic indices of diastolic function were obtained, and dysfunction
      was assumed when at least two values differed by > or =2 SD from the normal
      weight group. RESULTS: In obese subjects, the values of maximum velocity of
      active mitral filling (A) were increased and pulmonary diastolic velocity was
      decreased significantly (p< 0,01); all other diastolic variables were unchanged.
      Subclinical diastolic dysfunction tend to be more prevalent among obese subjects
      but it was not significantly different from non obese (p= 0.11), being present in
      nine obese (20.5%) and 4 normal (8.9%) subjects. CONCLUSION: Subclinical left
      ventricular diastolic dysfunction is present in obese women.

PMID- 16799209
TI  - The correlation between insulin resistance and left ventricular systolic function
      in obese women.
AB  - AIM: To determine the correlation between insulin resistance and left ventricular
      systolic function in obese women. METHODS: 44 obese (BMI > or =25 kg/m2) and 45
      normal weight women were studied. They had no other pathological conditions.
      Echocardiograms were undertaken in our echocardiographic laboratory following
      standard methods. The homeostasis model was used to assess insulin resistance
      (HOMA IR). RESULTS: Ejection fraction (p =0.22) and fractional shortening (p=
      0.58) were not difference between obese women and the normal group. There was no
      correlation between insulin resistance and left ventricular systolic function.
      CONCLUSION: There was no correlation between insulin resistance and left
      ventricular ejection fraction.

PMID- 16799210
TI  - Postural shortening due to primary hyperparathyroidism caused by parathyroid
      adenoma.
AB  - Osteoporosis can be primary or secondary. Secondary osteoporosis is the result of
      an underlying disease such as an endocrine abnormality, and an example of such is
      primary hyperparathyroidism. The most common cause of primary hyperparathyroidism
      is parathyroid gland adenoma. The diagnosis of primary hyperparathyroidism is
      based on the following biochemical examinations: parathyroid hormone, serum
      calcium, creatinine clearance, 24 hour urinary calcium, and another examination
      such as parathyroid gland scan. This is a rare case of an adult man who presented
      with a chief complaint of decreasing body height, back pain, difficulty in taking
      deep breaths and difficulty in his activities. The patient was diagnosed with
      primary hyperparathyroidism caused by parathyroid gland adenoma. His complaint
      was reduced after parathyroidectomy. His new complaint was that his tooth can be
      pulled out easily. We found high levels of parathyroid hormone and low levels of
      serum calcium caused by secondary hyperparathyroidism.

PMID- 16799211
TI  - Albumin cobalt binding (ACB) test: its role as a novel marker of acute coronary
      syndrome.
AB  - The biochemical marker of myocardial ischemia is detected prior to the
      development of myocardial necrosis, i.e. a novel biochemical evaluation based on
      human serum albumin binding to cobalt, a transitional metal. The evaluation is
      known as Albumin Cobalt Binding (ACB) Test. ACB Test is applied to detect the
      presence of Ischemia Modified Albumin (IMA), an albumin which has altered binding
      capacity to bind metal ion such as cobalt (Co), copper (Cu) and nickel (Ni) in N
      terminus region. It is produced when the serum albumin convenes with ischemic
      heart tissues. ACB Test detecting the presence of myocardial ischemia that occurs
      prior to myocardial necrosis has been studied by some researchers and they found
      an ACB increase prior to troponin increase. The cut off point of ACB evaluation
      was 85 U/ml. Provided that the value was greater than 85 U/ml then there was
      positive myocardial ischemia. But it should be noticed that IMA increase in the
      plasma may be due to other tissues such as gastrointestinal tissues or skeletal
      muscles tissues. We should also consider other factors which may affect the
      evaluation result such as severe hypoalbuminemia that will cause a false-high
      result. ACB Test may be used as an early marker of myocardial ischemia that
      occurs prior to myocardial necrosis.

PMID- 16799212
TI  - Prevention of cardiovascular disease in diabetes mellitus: by stressing the CARDS
      study.
AB  - Recently, diabetes mellitus has become a global epidemic disease. There is a
      study indicating that type 2 diabetes mellitus (DM) is frequently found in
      children and teenager. Furthermore, in some countries, it is more frequent than
      type 1 diabetes mellitus.1 WHO stated that in the year of 2000, there were 177
      million diabetes mellitus patient in the world and it is predicted that in the
      year of 2030, it will be increased to 366 million.2 This is very problematical
      for some countries such as India, People's Republic of China and Indonesia where
      the prevention and treatment facilities are still inadequate. To date, Indonesia
      has occupied the 4th rank, with predicted number of diabetes mellitus patient
      about 8.4 million and this number will be increased to 21.3 million in the year
      of 2030. There is no data about the number of patient with metabolic syndrome
      (MS) and insulin resistance syndrome (IR), but it should be higher than the
      number of diabetic patient. As we all have known, these conditions are the high
      risk condition of diabetes mellitus development.2 One of reasons concerning why
      prevalence and pre-diabetic condition are increased (including the increased MS)
      is rising obesity frequency. In the United States, over 60% of recent adult
      population are overweight, which is defined as "body mass index" (BMI) 25; and
      about 30% of them have obesity, which is defined as BMI 30%.3 If diabetes
      mellitus occurred, cardiovascular disease (CVD) including coronary heart disease
      (CHD) also may occur. It is important to prevent the diabetes mellitus as well as
      to prevent the complication risk of CVD in diabetic patient.

PMID- 16799213
TI  - Expanded case definition for diagnosing extrapulmonary tuberculosis in HIV
      infected person.

PMID- 16799214
TI  - Coagulopathy in dengue infection and the role of interleukin-6.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in
      host defense due to its wide range of immune and hematopoietic activities and
      also its potential ability to induce the acute phase response. The high
      concentration of IL-6 has implication in the pathology of some diseases
      especially in DHF/DSS patients. This cytokine play a crucial role in the enhanced
      production of anti-platelet or anti-endothelial cell auto antibodies local or
      systemic, elevated levels of tPA, as well as a deficiency in coagulation, leading
      to plasma leakage and bleeding. We describe the pathogenic, characteristic and
      mechanism of IL-6 during DV infection.

PMID- 16799216
TI  - Large outbreak of Salmonella Typhimurium DT104, the Netherlands, September
      November 2005.

PMID- 16799215
TI  - Clinical tuberculosis problems and management.
AB  - Tuberculosis (TB) is a chronic disease caused by M. tuberculosis. WHO (World
      Health Organization) 1993 has estimated that one third of world population has
      been infected by M. tuberculosis bacillus. It is also estimated that 8 million
      people contract the disease annually and two to three million deaths occur every
      year due to TB. Major factors that have aggravated the spread of TB are: 1)
      ineffective TB control programs, leading to the development of multi drug
      resistant bacilli, 2) co infection with HIV (human immunodeficiency virus) where
      TB progress rapidly and deadly,3) existence of other co-morbid that need higher
      expert (Internist etc). Vaccination with BCG does not seem to protect the adult
      population consistently and effectively from developing pulmonary TB, and has had
      no significant impact on the global TB epidemiology. Tuberculosis in Indonesia
      results in high death rate because it is the second highest infection with
      national prevalence rate of 0.24%. Effective medicine standard of anti
      tuberculosis is available, but many obstacles in the program from lack of
      knowledge among health officers, low consciousness and compliances of person with
      tuberculosis to carry out the treatment schedule and so on make the success of TB
      eradication unsatisfied. Clinical appearances of TB are multiple with non
      specific symptoms, the cases that are exposed to similar source of infection but
      will show different clinical consequence from mild to severe. Nevertheless, with
      the rise of multi drug resistance strains of M. tuberculosis, the spread of HIV
      infection and the variation of BCG efficacy, the search for more powerful drugs,
      more effective vaccines, better diagnostics and other intervention strategies
      have become an urgent goal worldwide. Also written here how to diagnose, choose
      of category of treatment, cocktail anti TB according the category and some clue
      in handling problems during treatment.

PMID- 16799217
TI  - Hepatitis A outbreak in a group of Danish tourists returning from Turkey, October
      2005.

PMID- 16799218
TI  - Shigella sonnei outbreak due to consumption of unpasteurised milk curds in
      Vilnius, Lithuania, 2004.

PMID- 16799220
TI  - On the use of CCD area detectors for high-resolution specular X-ray reflectivity.
AB  - The use and application of charge coupled device (CCD) area detectors for high
      resolution specular X-ray reflectivity is discussed. Direct comparison of high
      resolution specular X-ray reflectivity data measured with CCD area detectors and
      traditional X-ray scintillator ('point') detectors demonstrates that the use of
      CCD detectors leads to a substantial (approximately 30-fold) reduction in data
      acquisition rates because of the elimination of the need to scan the sample to
      distinguish signal from background. The angular resolution with a CCD detector is
      also improved by a factor of approximately 3. The ability to probe the large
      dynamic range inherent to high-resolution X-ray reflectivity data in the specular
      reflection geometry was demonstrated with measurements of the orthoclase (001)-
      and alpha-Al2O3 (012)-water interfaces, with measured reflectivity signals
      varying by a factor of approximately 10(6) without the use of any beam
      attenuators. Statistical errors in the reflectivity signal are also derived and
      directly compared with the repeatability of the measurements.

PMID- 16799221
TI  - A high-throughput determination of metal concentrations in whole intact
      Arabidopsis thaliana seeds using synchrotron-based X-ray fluorescence
      spectroscopy.
AB  - The identification of genes involved in metal metabolism in plants requires the
      'screening' of thousands of genetic variants. While inductively coupled plasma
      mass-spectroscopy has been used to identify variants with an altered total metal
      concentration, a more convenient high-throughput technique capable of examining
      individual seeds (or other tissues) would be useful. Here, the high brightness of
      synchrotron radiation has been utilised to examine relative metal concentrations
      in seeds of the genetically well characterised plant Arabidopsis thaliana. The
      relative concentrations of Mn, Fe, Ni, Cu and Zn in individual seeds were
      determined using a 500 microm x 500 microm beam. Metal concentrations were
      normally distributed, except where metal-containing dust contaminated the
      samples. Neither seed orientation nor genetic background (from three 'wild type'
      variants with different genetic lineages) had a significant affect on the Zn
      normalised metal concentration. No advantages, such as the observation of tissue
      specific metal accumulation, were obtained by using a 50 microm x 50 microm beam.
      A high-throughput proof-of-concept experiment was demonstrated that could be used
      to screen libraries of genetic variants for individuals with altered metal
      concentrations. Further work is required to standardise the technique before
      screening of libraries is possible.

PMID- 16799222
TI  - Fluorescence X-ray absorption spectroscopy using a Ge pixel array detector:
      application to high-temperature superconducting thin-film single crystals.
AB  - A Ge pixel array detector with 100 segments was applied to fluorescence X-ray
      absorption spectroscopy, probing the local structure of high-temperature
      superconducting thin-film single crystals (100 nm in thickness). Independent
      monitoring of pixel signals allows real-time inspection of artifacts owing to
      substrate diffractions. By optimizing the grazing-incidence angle theta and
      adjusting the azimuthal angle phi, smooth extended X-ray absorption fine
      structure (EXAFS) oscillations were obtained for strained (La,Sr)2CuO4 thin-film
      single crystals grown by molecular beam epitaxy. The results of EXAFS data
      analysis show that the local structure (CuO6 octahedron) in (La,Sr)2CuO4 thin
      films grown on LaSrAlO4 and SrTiO3 substrates is uniaxially distorted changing
      the tetragonality by approximately 5 x 10(-3) in accordance with the
      crystallographic lattice mismatch. It is demonstrated that the local structure of
      thin-film single crystals can be probed with high accuracy at low temperature
      without interference from substrates.

PMID- 16799223
TI  - Einstein and Debye models for EXAFS parallel and perpendicular mean-square
      relative displacements.
AB  - The correlated Einstein and Debye models for EXAFS parallel mean-square relative
      displacement (MSRD) are derived from the general expression in terms of
      eigenfrequencies and eigenvectors of the dynamical matrix, without ad hoc
      assumptions. The two models are generalized to parameterize also the EXAFS
      perpendicular MSRD. The physical meaning of Einstein frequencies, as well as the
      application of the Debye model to crystals with more than one atom per cell, are
      critically discussed.

PMID- 16799224
TI  - Combustion front dynamics in the combustion synthesis of refractory metal
      carbides and di-borides using time-resolved X-ray diffraction.
AB  - A compact diffraction-reaction chamber, using a 2-inch photodiode array detector,
      has been employed to investigate the chemical dynamics at the combustion front of
      a selected series of refractory metal carbides and di-borides from their
      constituent element reactants as well as binary products from B4C as a reactant.
      These systems are denoted as (i) M + C --> MC; (ii) M + 2B --> MB2; and (iii) 3M
      + B4C --> 2MB2 + MC, where M = Ti, Zr, Nb, Hf or Ta. Time-resolved X-ray
      diffraction using intense synchrotron radiation at frame rates up to 10 frames s(
      1) (or 100 ms frame(-1)) was employed. The combustion reactions were found to
      complete within 200-400 ms. In contrast to the Ta + C --> TaC combustion system
      studied earlier, in which a discernible intermediate sub-carbide phase was first
      formed, reacted further and disappeared to yield the final TaC product, no
      intermediate sub-carbide or sub-boride was detected in the current systems.
      Combustion for the Ti, Zr and Hf systems involved a liquid phase, in which the
      adiabatic temperatures Tad are well above the melting points of the respective
      reactant metals and have a typical combustion front velocity of 5-6 mm s(-1). The
      Nb and Ta systems have lower Tad, involving no liquid phase. These are truly
      solid combustion systems and have a lower combustion front velocity of 1-2 mm s(
      1). The current study opens up a new avenue to chemical dynamics and macrokinetic
      investigations of high-temperature solid-state reactions.

PMID- 16799225
TI  - Theory and characteristics of transition radiation emitted by low-energy storage
      ring synchrotrons for use in X-ray lithography.
AB  - Existing theory is developed further for description of transition radiation (TR)
      emitted by low-energy storage-ring synchrotrons. It takes into account the fact
      that the dielectric constant of the TR target material is a complex function,
      introduces an expression for the number of passes of an injected electron through
      the target, and accounts more precisely for the absorption of TR. It is shown
      that the consideration of the complexity of the dielectric constant results in
      notable changes of the TR spectrum for emitted photons with energies close to the
      ionization energies of the target material. Since such TR is used mostly for
      performing X-ray lithography (XRL), the sensitivity of the photoresist used in
      XRL is formulated. Maximization of this resist sensitivity can be used for
      designing optimum targets for XRL. Study of the transmission of TR through a
      commonly used XRL mask, and its partial absorption in a common photoresist,
      illustrates that TR emission with E = [490, 1860] eV is most useful for
      performing such XRL, while E approximately equal to 1 keV is best. It is shown
      that, for a particular target material, a target consisting of only one foil
      emits the most TR energy. Optimization of an Al target, based on maximization of
      the resist sensitivity, indicates that a target containing one Al foil with a
      thickness of about 200 nm would be best for performing XRL by our low-energy
      storage-ring synchrotron MIRRORCLE-20SX.

PMID- 16799226
TI  - Sharp-focusing Bragg-Fresnel zone plate with Laue diffraction geometry.
AB  - The impact of decreased zone height on the focal properties of hard X-ray Bragg
      Fresnel zone plates has been studied by numerical simulation. Decreased zone
      height allows for smaller zone widths and, although the efficiency of the lens is
      decreased, the signal-to-background ratio in the focal plane of the lens remains
      at a comparatively high level. This is distinct from an analogous case of
      ordinary phase zone plates.

PMID- 16799229
TI  - Assessment of genetic effects of polymorphisms in the MCP-1 gene on serum MCP-1
      levels and myocardial infarction in Japanese.
AB  - BACKGROUND: Recently, the Framingham Heart Study reported that genetic variations
      in CCL2 influence serum levels of monocyte chemoattractant protein-1 (MCP-1) and
      the incidence of myocardial infarction (MI). The purpose of the present study was
      to investigate the possible involvement of CCL2 in the pathogenesis of
      atherosclerosis and MI in Japanese. METHODS AND RESULTS: Multiple regression
      analysis indicated that the MCP-1 levels were significantly influenced by various
      factors including age, body mass index, smoking, alcohol intake, high density
      lipoprotein-cholesterol, and systolic blood pressure. Moreover, the serum MCP-1
      level was significantly correlated with intima - media thickness (p < 0.0001).
      However, this association disappeared when other clinical confounding factors
      were included in the analyses. Comprehensive analysis of common polymorphisms of
      CCL2 in a large community-based population and in subjects with MI found that the
      A(-2138)T polymorphism affected the serum MCP-1 level in a subgroup of subjects
      65 years and older. However, no significant differences in the frequencies of any
      of the polymorphisms or haplotypes were found between subjects with and without
      MI. None of the polymorphisms in CCL2 affected carotid atherosclerosis.
      CONCLUSIONS: The serum MCP-1 level was a good surrogate marker of atherosclerosis
      in the present study population. Although genetic variations in CCL2 may have
      some influence on MCP-1 production, their influence does not seem to contribute
      appreciably to atherosclerosis in Japanese. The present results did not support
      the recently published findings from the Framingham Heart Study. The discrepancy
      between the 2 studies may be related to differences in confounding factors that
      contribute to MCP-1 levels and in the haplotype structure of the 2 populations.

PMID- 16799230
TI  - Gender difference in coronary events in relation to risk factors in Japanese
      hypercholesterolemic patients treated with low-dose simvastatin.
AB  - BACKGROUND: Gender differences between the risk factors for coronary heart
      disease and coronary events were examined in the Japan Lipid Intervention Trial,
      a 6-year observational study. METHODS AND RESULTS: Men (12,575) and women
      (27,013) were analyzed for risk of coronary events (acute myocardial infarction
      and sudden cardiac death). Simvastatin reduced serum low-density lipoprotein
      cholesterol (LDL-C) by 27% in both genders, and increased serum high-density
      lipoprotein cholesterol (HDL-C) in men (5%) and women (4%). The incidence of
      coronary events was lower in women (0.64/1,000 patient-years) than in men
      (1.57/1,000 patient-years). The risk of coronary events increased by 18% in men
      and 21% in women with each 10 mg/dl elevation of LDL-C, and decreased by 39% in
      men and 33% in women with each 10 mg/dl elevation of HDL-C. The risk increased
      proportionally with aging in women, but not in men. Diabetes mellitus (DM) was
      more strongly related to the risk of coronary events for women (relative risk
      3.07) than for men (relative risk 1.58). CONCLUSIONS: The incidence of coronary
      events is lower in women. Serum LDL-C is related to an increased risk of coronary
      events to the same extent in both genders. DM seems to be a more important risk
      factor in women, trading off the lower risk of coronary events among them.

PMID- 16799231
TI  - Association of Chlamydia pneumoniae infection and carotid intima-media wall
      thickness in Japanese Americans.
AB  - BACKGROUND: Chlamydia pneumoniae (Cp) infection has been proposed as a risk
      factor for coronary artery disease (CAD), but it remains unclear whether Cp plays
      a role in the progression of early stage carotid atherosclerosis. METHODS AND
      RESULTS: The associations among Cp IgG/IgA antibodies, inflammation markers such
      as C-reactive protein (CRP) and interleukin (IL)-6, and the maximal progression
      of carotid intima-media wall thickness (max IMT) were evaluated using
      ultrasonography in 259 Japanese Americans. The presence of Cp IgG or IgA
      antibodies itself did not show significant correlation with max IMT after
      adjustment for age and sex. However, in the Cp IgG seropositive group, the
      subjects with high IL-6 levels showed more pronounced max IMT progression than
      those with low IL-6 levels after adjustment of the other CAD risk factors.
      Moreover, in the Cp IgA seropositive group, the subjects with high CRP or IL-6
      levels had significantly higher levels of max IMT compared with those with low
      CRP or IL-6. CONCLUSIONS: The results support the hypothesis that a chronic
      latent Cp infection with inflammation might accelerate the development of early
      stage atherosclerotic lesions.

PMID- 16799232
TI  - Prevalence of low HDL-cholesterol levels and associated factors among Koreans.
AB  - BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDL-C), as well
      as high levels of low-densi-ty lipoprotein cholesterol, play a crucial role in
      the development of cardiovascular disease, which has shown a remarkable increase
      in Korea. METHOD AND RESULTS: Data were obtained from the 1998 Korean National
      Health and Nutrition Examination Survey, which was a cross-sectional national
      health survey. The total study population amounted to 7,300 individuals (3,283
      men, 4,617 women), aged 18 years and older. The prevalence of low HDL-C levels,
      as proposed by National Cholesterol Education Program Adult Treatment Panel III
      or International Diabetes Federation, was 23.8% in men and 47.5% in women. After
      adjusting for independent variables, there was a greater risk of low HDL-C with
      an increased body mass index, abdominal obesity, cigarette smoking, and decreased
      alcohol consumption. Physically inactive lifestyle in men and low fat intake in
      women were identified as factors associated with low HDL-C level. CONCLUSIONS:
      The prevalence of low HDL-C levels is relatively high among Koreans, which may
      have important implications for public health. Identified associated factors
      should be considered for reducing the risk of low HDL-C levels in Koreans.

PMID- 16799233
TI  - Location of out-of-hospital cardiac arrests in Takatsuki City: where should
      automated external defibrillator be placed.
AB  - BACKGROUND: Public access defibrillation has been introduced to improve the
      outcome of patients experiencing out-of-hospital cardiac arrest (OHCA). The aim
      of this study was to examine the best location for automated external
      defibrillators (AED). METHODS AND RESULTS: All patients who were resuscitated
      after OHCA by emergency medical technicians in Takatsuki City over 6 years were
      enrolled. The annual incidence of OHCA and the number of 1-year survivors with
      good neurological outcome in each of 21 sub-location categories were
      investigated, as well as the ratio of ventricular fibrillation (VF) as the
      initial rhythm to the total OHCA in each of 5 location categories. In total,
      there were 1,112 patients with OHCA, 62 (5.6%) with VF and 14 (1.3%) with good
      neurological outcome. The annual incidence of cardiac arrest (CA) per site was
      the highest in railway stations (0.3000), followed by hospitals (0.1802), homes
      for the aged (0.1115), playgrounds (0.0769) and golf courses (0.0667). However,
      none of the patients experiencing CA at railway stations, homes for the aged and
      golf courses had a good neurological outcome. The ratio of VF to total CA was the
      highest in the workplace (35.3%). CONCLUSIONS: The 6 locations, including
      workplace, are recommended as appropriate locations for AED.

PMID- 16799234
TI  - Long-term efficacy of edaravone in patients with acute myocardial infarction.
AB  - BACKGROUND: The effect of edaravone, a free radical scavenger, on long-term
      prognosis and its efficacy with regards to scavenging injurious free radicals in
      patients with acute myocardial infarction (AMI) was examined. METHODS AND
      RESULTS: One hundred and one initial AMI patients were randomly assigned to
      receive 30 mg edaravone (n = 50) or a placebo (n = 51) intravenously just before
      reperfusion. The infarct size, using serum biomarkers and Q-wave formations, and
      the incidence of reperfusion arrhythmia between the groups were compared.
      Cardiovascular event-free curves were estimated by using the Kaplan - Meier
      method. In addition, the serum thioredoxin levels, an oxidative stress marker, to
      assess the antioxidant effect of edaravone was determined. In all cases,
      successful reperfusion was obtained within 6 h after the onset of symptoms.
      Infarct size and reperfusion arrhythmia were significantly attenuated in the
      edaravone group compared with the placebo group (p = 0.035 and p = 0.031). The
      cumulative event-free rate was significantly higher in the edaravone group than
      in the placebo group (p = 0.045). Serum thioredoxin levels were significantly
      lower in the edaravone group than in the placebo group throughout the acute
      phase. CONCLUSIONS: The present study suggests that the edaravone administration
      just prior to reperfusion might reduce oxidative stress and improve the long-term
      clinical outcomes of AMI patients.

PMID- 16799235
TI  - Strong correlation between serum levels of inflammatory mediators and their
      distribution in infarct-related coronary artery.
AB  - BACKGROUND: Little is known regarding the correlation between circulating levels
      of inflammatory mediators and their distribution within the infarct-related
      coronary artery (ICA). METHODS AND RESULTS: Atherothrombotic tissue and blood
      were aspirated by export suction catheter from the ICA in 49 patients with an
      acute myocardial infarction (AMI) < 6 h duration who underwent primary
      percutaneous coronary intervention (PCI). Blood samples were collected before PCI
      for levels of high-sensitivity (hs) C-reactive protein (CRP), soluble P-selectin
      (sP-selectin) and white blood cell (WBC) counts. Immunohistochemical staining was
      performed for localization of CRP within the ICA. Staining intensity was graded
      for macrophage and extracellular tissue (0: no staining; 1+: < 30%, 2+: 30% to
      60%, and 3+: > 60%). The hs-CRP levels were markedly higher in grade 3+ compared
      with both grade 2+ and grade 1+ of macrophage and extracellular staining of CRP
      (all p values < 0.0001), and in grade 2+ compared with grade 1+ (p < 0.001).
      Additionally, the ICA had a significantly higher sP-selectin level and WBC count
      compared with the systemic circulation (p < 0.0001). Furthermore, the ICA level
      of sP-selectin was noticeably higher in patients with a total atherothrombus
      volume > or = 0.5 cm3 than in patients with total volume < 0.5 cm3 (p < 0.0001).
      Moreover, correlation analysis demonstrated that the increase in the ICA level of
      sP-selectin was significantly related to the increase in the WBC count in the
      artery (r = 0.548, p < 0.0001). Multiple analysis identified an increased
      circulating level of hs-CRP as the only independent predictor of > or = 2+ in
      macrophage (p < 0.0001) and > or = 2+ in extracellular (p < 0.0001) staining of
      CRP. CONCLUSIONS: Following AMI, the sP-selectin level and WBC count were
      markedly higher in the ICA than in the circulation. Moreover, the circulating
      level of hs-CRP was strongly associated with ICA localization of CRP.

PMID- 16799236
TI  - Sustained attenuation of neointimal coverage over the stent following
      brachytherapy for in-stent restenosis: angioscopic findings.
AB  - BACKGROUND: The nature of the vessel lumen following vascular brachytherapy (VBT)
      has not been extensively explored in the clinical setting. METHODS AND RESULTS:
      By using angioscopy, 33 stents treated with percutaneous balloon angioplasty with
      or without VBT for in-stent restenosis after 8.9 +/- 2.1 months of the treatment
      were followed (VBT =14 lesions; control =19 lesions). Neointimal coverage, stent
      attachment, and the presence of red or white thrombi were factors that were
      assessed. The majority of the stents (74%) were fully covered with non
      transparent neointima in the control group. In contrast, stent struts were
      clearly seen in 57% lesions with VBT. The absence of neointima with glittering
      stent struts were only seen in 29% of lesions in VBT (p = 0.03). Incomplete stent
      attachment was not detected in the controls, whereas 14% were in VBT (p = 0.17).
      Red thrombi were observed in 14% with VBT and in 16% in controls, which showed
      that there was a similar incidence regardless of the treatment. Neither exposure
      of stent struts (p = 0.5) nor incomplete stent attachment (p = 1.0) was related
      to thrombi. CONCLUSIONS: The exposure of stent struts and incomplete stent
      attachment were occasionally observed by angioscopy even 9 months after VBT for
      the treatment of in-stent restenosis.

PMID- 16799237
TI  - Elevated plasma osteopontin levels were associated with osteopontin expression of
      CD4+ T cells in patients with unstable angina.
AB  - BACKGROUND: Plaque instability in patients with unstable angina (UA) is
      associated with stimulated CD4+ T cells, so the present study investigated
      whether there is a relationship among plaque instability, osteopontin and CD4+ T
      cells. METHODS AND RESULTS: Peripheral blood mononuclear cells were collected
      from 51 consecutive patients with UA, 60 patients with stable angina (SA), and 39
      patients with chest pain syndrome (CPS). Osteopontin-producing CD4+ T cells were
      quantified by flow cytometry. Plasma osteopontin levels (ng/ml) were measured by
      ELISA and were higher in patients with UA (792.0 +/- 316.7) than in those with SA
      (626.0 +/- 195.0, p < 0.005) or CPS (594.7 +/- 239.4, p < 0.005). The frequency
      (%) of osteopontin-producing CD4+ T cells was higher in patients with UA (26.7 +/
      13.3) than in those with SA (19.5 +/- 11.1, p < 0.05) or CPS (16.6 +/- 9.0, p <
      0.005). Furthermore, the plasma osteopontin level correlated with the frequency
      of osteopontin-producing CD4+ T cells (r = 0.327, p = 0.0004), as did the high
      sensitivity C-reactive protein level (r = 0.360, p = 0.0002). CONCLUSIONS: The
      plasma osteopontin levels are elevated in patients with UA, accompanied by an
      increase in the number of osteopontin-production of circulating CD4+ T cells.
      Circulating CD4+ T cells may play a role through osteopontin in the
      pathophysiology of UA.

PMID- 16799238
TI  - Prediction of mortality by high-sensitivity C-reactive protein and brain
      natriuretic peptide in patients with dilated cardiomyopathy.
AB  - BACKGROUND: The prognostic role of serum C-reactive protein (CRP) in chronic
      heart failure (CHF) patients, especially those with nonischemic dilated
      cardiomyopathy (DCM), remains unknown. In the present study, whether CRP provides
      prognostic information in DCM patients was evaluated. METHODS AND RESULTS:
      Neurohumoral factors and hemodynamics in 84 consecutive DCM patients were
      measured and these patients were followed up for a mean period of 42 months.
      During the follow-up period, 23 patients developed cardiac events and 18 patients
      died of cardiac causes. Using stepwise multivariate Cox proportional hazards
      regression analyses, log brain natriuretic peptide (BNP) (p = 0.007) and high
      sensitivity CRP (hsCRP) > 1 mg/L (p = 0.008) were significant independent
      predictors of cardiac events. The patients were stratified into 4 groups based on
      the normal serum concentration of hsCRP (1 mg/L) and median plasma concentration
      of BNP (110 pg/ml). Survival rates were significantly higher in patients with
      hsCRP < 1 mg/L and BNP < 110 pg/ml. The hazard ratio of patients with BNP > 110
      pg/ml and hsCRP > 1 mg/L was 15.8 (95% confidence interval, 1.9-127.2) compared
      with those with BNP < 110 pg/ml and hsCRP < 1 mg/L for cardiac death.
      CONCLUSIONS: Serum hsCRP level is an independent prognostic predictor in patients
      with DCM and the combination of hsCRP and BNP may be useful for the management of
      CHF patients with DCM.

PMID- 16799239
TI  - Effect of physical training on insulin resistance in patients with chronic heart
      failure.
AB  - BACKGROUND: The effect of physical training on insulin resistance (IR) in chronic
      heart failure (CHF) remains unclear. METHODS AND RESULTS: Fourteen patients with
      CHF performed physical training using a bicycle ergometer; 9 patients (64%) were
      hyperinsulinemic and insulin resistant (HOMA IR > 1.97). Exercise tolerance
      increased (5.1 +/- 1.7 to 6.9 +/- 2.7 METs, p < 0.05) and heart rate at rest
      decreased (82 +/- 15 to 72 +/- 6, p < 0.05) in the IR group after physical
      training. Physical training also decreased the insulin level (15.1 +/- 5.6 to 9.8
      +/- 2.6 microU/ml, p < 0.05) and HOMA IR (3.7 +/- 1.4 to 2.3 +/- 0.6, p < 0.05)
      in the IR group, but not in the 5 patients (36%) without IR or in 6 control
      patients. CONCLUSION: Physical training can improve hyperinsulinemia and IR in
      patients with CHF.

PMID- 16799240
TI  - Quantitative assessment of left ventricular function during contrast-enhanced
      dobutamine stress echocardiography predicts future cardiac events in diabetic
      patients.
AB  - BACKGROUND: Non-invasive diagnosis and risk stratification of coronary artery
      disease are important for the selection and optimization of therapeutic
      interventions in diabetic patients, which may improve survival. The aim of this
      study was to determine the incremental value of contrast-enhanced dobutamine
      stress echocardiography (CE-DSE) for risk stratification. METHODS AND RESULTS: CE
      DSE was performed in 326 patients with diabetes mellitus (mean age; 66 +/- 10
      years, 223 men). All patients were followed up for a mean of 29 months (1-61
      months). Dobutamine was infused in a standard protocol with an intravenous
      contrast agent. The primary endpoints for hard cardiac events included cardiac
      death and nonfatal myocardial infarction. The primary endpoints for total cardiac
      events included hard cardiac events, unstable angina pectoris, congestive heart
      failure, and late coronary revascularization (> 3 months). Cardiac events
      occurred in 74 patients. The addition of the CE-DSE results, including abnormal
      left ventricular end-systolic volume response and left ventricular ejection
      fraction at peak stress < 50%, to the clinical and rest echocardiography model
      provided incremental information in predicting total cardiac events (increase in
      chi-square value for the model from 17 to 24, p < 0.05) and hard cardiac events
      (increase in chi-square value for the model from 18 to 24, p < 0.05).
      CONCLUSIONS: Quantitative assessment of left ventricular function during CE-DSE
      provides incremental prognostic information in predicting cardiac events in
      diabetic patients.

PMID- 16799241
TI  - Morphologic characteristics of hypertrophic cardiomyopathy of the elderly with
      cardiac myosin-binding protein C gene mutations.
AB  - BACKGROUND: Several morphologic distinctions between elderly and young patients
      with hypertrophic cardiomyopathy (HCM) have been reported. In particular, a
      crescent-shaped left ventricular (LV) cavity with reversed septal curvature,
      which is often seen in young patients, is rare in elderly patients. However,
      those studies were carried out before gene testing became available and
      heterogeneous causes or age-related changes may have been included. The purpose
      of this study was to determine the morphologic characteristics of elderly
      patients with HCM definitely caused by a mutation in the cardiac myosin-binding
      protein C (MyBPC). METHODS AND RESULTS: Twenty-seven patients with HCM caused by
      MyBPC gene abnormality were evaluated. Patients were divided into an elderly
      group (> or = 65 years of age, n = 8) and a young group (< 65 years of age, n =
      19). LV hypertrophy was milder in the elderly than in the young for maximum LV
      wall thickness (18 +/- 5 mm vs 24 +/- 6 mm, p = 0.008) and Wigle score (5.7 +/-
      1.5 vs 7.6 +/- 1.6, p < 0.005). However, an abnormal crescent-shaped LV was
      similarly prominent in both groups (75% in the elderly vs 95% in the young, p =
      NS). None of the elderly patients showed a proximal septal bulge. CONCLUSIONS: An
      abnormal crescent-shaped LV cavity was frequently present in the elderly as in
      the young when there are MyBPC mutations. It is possible that this morphologic
      feature could become useful for determining the etiology of HCM in elderly
      patients.

PMID- 16799242
TI  - Age-related hemodynamic and morphologic differences in patients undergoing
      alcohol septal ablation for hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Alcohol septal ablation (ASA) decreases the left ventricular (LV)
      outflow gradient and relieves symptoms in patients with highly symptomatic
      hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study was to
      evaluate the early course of hemodynamic, morphologic and clinical changes in
      younger and elderly patients. METHODS AND RESULTS: Forty-four consecutive
      patients (age, 24-81 years) underwent the ASA procedure for HOCM. Clinical and
      echocardiographic data were obtained at baseline and periodically up to 12 months
      after ASA. There was a significant correlation between septum thickness and age
      at baseline and in the early post procedural period (p = 0.004 at baseline, p =
      0.0033 days postoperative, p = 0.0193 weeks pos operative). The dependence of
      septal thickness on the duration of follow-up (p < 0.001) was significantly
      influenced by age (p = 0.026), which retained statistical significance after
      multivariate adjustment (p = 0.031). A decrease in the gradient of the LV outflow
      was identified in all age-related groups of patients (p < 0.001). After
      multivariate adjustment, there was a significant influence of age (p = 0.003) and
      creatine kinase-MB peak (p = 0.016) on the course of outflow gradient reduction.
      CONCLUSIONS: ASA is an effective treatment option for patients with HOCM,
      irrespective of their age. Younger patients are characterized by a thicker basal
      septum at baseline and a slower hemodynamic improvement within the early post
      procedural period.

PMID- 16799243
TI  - Gender-related association of serum uric acid and left ventricular hypertrophy in
      hypertension.
AB  - BACKGROUND: The aim of the present study was to determine whether sex differences
      contribute to the association of serum uric acid and left ventricular hypertrophy
      in individuals with hypertension. METHODS AND RESULTS: Seventy participants with
      essential hypertension (34 men, 36 women; 54.4 +/- 1.6 years old) were enrolled
      to undergo echocardiography to calculate the left ventricular mass index (LVMI).
      Twenty-four-hour ambulatory blood pressure monitoring was done to assess blood
      pressure level precisely. The LVMI was significantly correlated with serum uric
      acid (r = 0.295, p = 0.013) in all participants. After controlling for factors
      such as age, sex, mean 24-h systolic blood pressure, creatinine clearance, and
      duration of hypertension, serum uric acid was still found to be significantly and
      independently associated with LVMI. Because serum uric acid was significantly
      higher in men than in women (6.8 +/- 0.3 and 5.1 +/- 0.2 mg/dl, respectively),
      subsequent analysis was performed by gender. Multiple regression analysis
      revealed that the LVMI was significantly and independently associated with serum
      uric acid in women, but not in men. CONCLUSIONS: The potential effect of uric
      acid on LV hypertrophy is more pronounced in female than in males with essential
      hypertension.

PMID- 16799244
TI  - Long-Term follow-up of the circadian rhythm of heart rate and heart rate
      variability in healthy elderly patients.
AB  - BACKGROUND: The long-term age-related changes in circadian rhythm of heart rate
      variability (HRV), that is, autonomic nervous activity, remain unknown in elderly
      people. METHODS AND RESULTS: Holter monitoring was conducted twice at an interval
      of 15 years in 15 healthy elderly patients (age: 70.0 +/- 4.1 years, at first
      monitoring, female: 10) and assessed the age-related changes in 24-h mean and
      hourly mean normal sinus R-R interval (mean NN), HRV (high frequency (HF)
      component, low frequency (LF) component and LF/HF) and the circadian rhythms. As
      a result, 24-h mean mean NN (0.976 +/- 0.115 vs 0.903 +/- 0.117 (s), p = 0.0019),
      LF/HF (1.681 +/- 0.731 vs 0.962 +/- 0.442, p = 0.0022), and LF (278.88 +/- 176.43
      vs 179.19 +/- 132.33 (ms2), p = 0.0039) significantly decreased 15 years later,
      although 24-h mean HF (221.20+/-138.89 vs 310.78+/-296.73 (ms2), p = 0.1102)
      increased slightly. The hourly mean NN closely correlated with hourly HF and
      LF/HF throughout circadian rhythms both at first and second monitoring. In the
      morning hours, amplitude rates of all HRV indices increased significantly 15
      years later. CONCLUSION: In elderly people, age-related changes in the 24-h mean
      heart rate (HR) were conversely dissociated from those of the 24-h mean HRV.
      However, the close correlation between hourly HR and HRV was preserved, even in
      very elderly patients. Additionally, the amplitude rates in HRV in the morning
      increased with age. These age-related changes of HR and HRV might be
      characteristic of elderly people.

PMID- 16799245
TI  - Bradycardia-dependent ECG changes in Brugada syndrome.
AB  - BACKGROUND: In patients with Brugada syndrome (BS), ventricular fibrillation (VF)
      occurs mainly during sleep; therefore, not only vagal activity but also
      bradycardia dependent changes in ECG may relate to the nighttime occurrence of
      VF. The present study aimed to examine the difference in bradycardia-dependent
      changes in the ECG of symptomatic and asymptomatic BS patients. METHODS AND
      RESULTS: Twenty-one patients with BS were categorized into symptomatic (n = 9)
      and asymptomatic (n = 12) groups. During the electrophysiologic study, the ECG
      changes were evaluated at RR intervals of 400, 600, 750, 1,000 and 1,100 ms
      during extrastimulation from the right atrium. The ST levels in V2, and the QT
      interval in both V2 and V5 were measured. Along with an increase in the RR
      interval from 400 to 1,100 ms, the ST levels in V2 increased in both groups; the
      increase did not differ between the 2 groups. In both leads V2 and V5, the
      prolongation of the QT interval along with an increase in the RR interval from
      400 to 1,100 ms was significantly smaller and the QT intervals at an RR interval
      of 1,100 ms were significantly shorter in the symptomatic than in the
      asymptomatic group. CONCLUSIONS: In patients with BS, the ST elevation was
      augmented during bradycardia to a similar extent in both symptomatic and
      asymptomatic patients. However, a inhibited prolongation of the QT interval
      during bradycardia was characteristic of symptomatic patients. These unique
      repolarization dynamics could relate to the nighttime occurrence of VF during
      bradycardia in patients with BS.

PMID- 16799246
TI  - Orthostatic decrease in cardiac chaos during the head-up tilt test in patients
      with vasovagal syncope.
AB  - BACKGROUND: Autonomic dysfunction contributes to orthostatic intolerance in
      vasovagal syncope (VVS), but as it has not been identified by spectral analysis
      of heart rate variability (HRV) in previous studies, the present hypothesis was
      that nonlinear analysis of HRV would identify the orthostatic intolerance in VVS.
      METHODS AND RESULTS: Twenty-six patients with VVS and 14 matched controls were
      subjected to 80-degree head-up tilt test (positive: 13 patients; negative: 13
      patients and 14 controls). There were no differences in the orthostatic changes
      in the indices of spectral analyses of HRV among the 3 groups. The Lyapunov
      exponent (LE) was calculated from 200 consecutive RR-intervals to investigate
      chaotic behavior, and cardiac chaos was defined as the incidence of the presence
      of a positive finite LE. Orthostatic decreases in cardiac chaos were observed in
      the VVS patients (both the positive and negative groups), although there was no
      orthostatic decrease in the control group (ANOVA: p = 0.008). The receiver
      operator characteristic curve indicated that cardiac chaos during the tilt
      identified VVS regardless of the results of the tilt (p < 0.001, sensitivity:
      85.7%, specificity: 96.2%). CONCLUSIONS: The decrease in cardiac chaos during the
      tilt test was specific to patients with VVS, even if their response to the test
      was negative.

PMID- 16799247
TI  - Impact of atrial septal defect closure on right ventricular performance.
AB  - BACKGROUND: Atrial septal defect (ASD) closure is one of the most representative
      cardiac operations, but there have been few assessments of right ventricular (RV)
      performance during the perioperative period. METHODS AND RESULTS: Using
      transesophageal echocardiography with automated border detection system, the RV
      pressure - area (P-A) loops were measured in 6 patients immediately before and
      after an ASD closure. Multiple RV P-A loops obtained by the inferior vena cava
      occlusion technique were used to evaluate end-systolic maximal elastance (Ees),
      preload recruitable stroke work (MEW), external work (EW) and the systolic P-A
      area (PAA). Ees and MEW are indices of contractility, and PAA represents the
      total mechanical energy. RV Ees and MEW did not change after the operation (from
      3.36 +/- 2.20 to 3.70 +/- 2.04 mmHg/cm2, p = 0.4; and from 10.3 +/- 5.0 to 10.5
      +/- 4.5 mmHg, p = 0.8, respectively), whereas EW and PAA were significantly
      reduced (from 121.4 +/- 77.4 to 48.7 +/- 26.6 mmHg/cm2, p < 0.05; and from 274.8
      +/- 212.8 to 92.7 +/- 52.8 mmHg/cm2, p < 0.05, respectively). ASD closure reduced
      the EW and total mechanical energy of the right ventricle without influencing
      contractility. CONCLUSIONS: These results indicate that ASD closure preserved RV
      function and reduced RV myocardial oxygen consumption. Assessment of the RV P-A
      relationship in the operating room demonstrates the beneficial effects of ASD
      closure on RV performance.

PMID- 16799249
TI  - Brief episode of myocardial ischemia before prolonged ischemia attenuates cardiac
      sympathetic nerve injury.
AB  - BACKGROUND: The aim of this study was to investigate the effects of brief
      ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief
      ischemia inhibits the sympathetic neural release of norepinephrine (NE) during
      subsequent sustained ischemia. However, whether it can attenuate the neural
      function after sustained ischemia remains unknown. METHODS AND RESULTS:
      Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine
      (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days
      prior to acute myocardial infarction. In the rat experiment, cardiac interstitial
      NE (iNE) with or without pretreatment of 5-min coronary ligation was determined
      during a 30-min occlusion. Differences between MIBG and Thallium-201 for the
      total defect score were significantly greater in Group II than in Group I (6.1 +/
      4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment
      (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic
      region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05)
      compared with rats without the pretreatment. CONCLUSION: A brief episode of
      ischemia attenuates the sympathetic neural injury caused by subsequent prolonged
      ischemia and this protective effect is associated with attenuation of NE release
      during the prolonged ischemia.

PMID- 16799248
TI  - Cross-bridge-dependent change of the Ca2+ sensitivity during relaxation in
      aequorin-injected tetanized ferret papillary muscles.
AB  - BACKGROUND The aim of the present study was to indicate the cross-bridge
      dependent change in the Ca2+ affinity of troponin-C (TnC) during relaxation in an
      intact preparation, because the intracellular mechanism of relaxation is not
      fully understood, although several methods of evaluating global diastolic
      function have been reported. METHODS AND RESULTS: The aequorin method was used
      with intact ferret papillary muscles and a tetanic contraction was induced by a
      repetitive electrical stimulation in the presence of ryanodine. The extra-Ca2+,
      the transient increase in the intracellular Ca2+ concentration in response to a
      rapid reduction in muscle length, which reflects the change in the Ca2+ affinity
      of TnC because of cross-bridge detachment, was measured, and the cross-bridge
      dependent change in the Ca2+ affinity of TnC was estimated by observing the
      change in the slope of the extra-Ca2+ -tension relation. The extra-Ca2+ -tension
      relation measured during relaxation became steeper than that during contraction
      in all cases. The extra-Ca2+ -tension relation became steeper in the presence of
      20 mmol/L caffeine during contraction in all cases. CONCLUSION: During
      relaxation, the downstream-dependent change in the Ca2+ affinity of TnC was
      enhanced, compared with that during contraction, because of a decrease in the
      number of attached cross-bridges.

PMID- 16799250
TI  - Epicardial ablation with cooled tip catheter close to the coronary arteries is
      effective and safe in the porcine heart if the ventricular potential is being
      monitored in the epicardium and endocardium.
AB  - BACKGROUND: Transthoracic epicardial ablation can be an alternative to
      conventional treatment for critical pathways of ventricular tachycardia located
      in the epicardium. However, the usefulness and safety of epicardial ablation
      close to the coronary arteries (CA) is not clear. The purpose of the present
      experimental animal study was to analyze the efficacy and safety of epicardial
      radiofrequency (RF) ablation close to the CA. METHODS AND RESULTS: Of the left
      ventricle-epicardium ablated sites, 35 lesions (20 with cooling and 15 without
      cooling) were close to the CA (left anterior descending artery < or = 15 mm) and
      33 lesions (23 with cooling and 10 without cooling) were further from the CA. For
      sites close to the CA, epicardial ablation was effective in 77% (15/20) with
      cooling and in 40% (6/15) without cooling. There was a significant difference of
      effective ablation between with cooling and without cooling (p < 0.05). For
      cooling, epicardial lesion size could be predicted by the change of endocardial
      ventricular potential using a basket catheter. No damage to major epicardial
      arteries was detected when the catheter tip was positioned 5 mm away from the CA.
      CONCLUSIONS: Close to the CA, RF ablation with cooling is more effective than RF
      without cooling and is safe if the ablation sites are located 5 mm away from the
      major CA.

PMID- 16799251
TI  - Novel mutation of plakophilin-2 associated with arrhythmogenic right ventricular
      cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterized
      by dilatation and akinesis of the right ventricle, and causes life-threatening
      ventricular arrhythmia. Mutations of plakophilin-2 (PKP2) have recently been
      identified as one causative abnormality in ARVC. A case of ARVC with a mutation
      of PKP2 is reported here. Direct sequencing of the patient's DNA revealed an
      insertion mutation in exon 8 of PKP2 (1728_1729insGATG). The mutation caused the
      frameshift and the premature termination of translation (R577DfsX5). This is the
      first case report of PKP2 mutation found in Japanese ARVC patients.

PMID- 16799252
TI  - Stent strut fracture-induced restenosis in a bifurcation lesion treated with the
      crush stenting technique.
AB  - Percutaneous treatment of a bifurcation lesion still shows a significant
      complication rate, mainly because of restenosis at the ostial site of the side
      branch vessel. Different techniques, such as V-stenting, culottes-stenting or
      crush stenting, allow full ostial coverage and may therefore achieve uniform drug
      distribution within the lesion. The crush technique results in a strong
      mechanical constraint on the side branch stent. A case of stent strut fracture
      induced restenosis in a bifurcation lesion treated with the crush stenting
      technique is described.

PMID- 16799253
TI  - Late outcome after repair of aortico-left ventricular tunnel: 10-year follow-up.
AB  - Despite successful surgical repair, patients with congenital aortico-left
      ventricular tunnel (ALVT) are at risk of developing aortic incompetence in the
      late postoperative period. Two cases of ALVT were followed for 10 years with
      special reference to aortic incompetence and geometry of the aortic root. The
      patients underwent repair of ALVT, one at 4 years of age and the other at 4
      months of age. The first patient had a slit-like tunnel (type I) and the aortic
      orifice was closed with a pericardial patch. The second patient had a large
      tunnel with an extracardiac aneurysm (type II) and was closed with a pericardial
      patch at the aortic orifice and a Dacron patch at the left ventricular orifice,
      thereby completely obliterating the tunnel. The last echocardiographic evaluation
      showed no residual flow in the tunnel and no aortic incompetence in case 1, but
      there was mild aortic valvular regurgitation with deformity of the right sinus in
      case 2. Careful long-term follow-up is necessary because patients with ALVT have
      some inherent structural abnormalities from the left ventricular outflow tract to
      the aortic root.

PMID- 16799254
TI  - Intracoronary injection of granulocyte colony-stimulating factor ameliorates the
      progression of left ventricular remodeling after myocardial ischemia/reperfusion
      in rabbits.
AB  - BACKGROUND: Although granulocyte colony-stimulating factor (G-CSF) is known to
      prevent left ventricular (LV) remodeling after acute myocardial infarction (AMI),
      the best method of administration is unknown. METHODS AND RESULTS: A rabbit
      ischemia/reperfusion model was created and G-CSF was administered into the
      coronary artery immediately after reperfusion. The LV size and contraction were
      determined by echocardiography, and the extent of infarcted myocardium was
      measured by Masson-Trichrome staining. The benefits of intracoronary injection of
      G-CSF on LV remodeling were similar to subcutaneous injection. CONCLUSIONS:
      Direct intracoronary G-CSF injection may become a new therapy for AMI with lower
      adverse effects.

PMID- 16799255
TI  - The emergence of a general theory of the initiation and strength of the
      heartbeat.
AB  - Sarcoplasmic reticulum (SR) Ca(2+) cycling, that is, the Ca(2+) clock, entrained
      by externally delivered action potentials has been a major focus in ventricular
      myocyte research for the past 5 decades. In contrast, the focus of pacemaker cell
      research has largely been limited to membrane-delimited pacemaker mechanisms
      (membrane clock) driven by ion channels, as the immediate cause for excitation.
      Recent robust experimental evidence, based on confocal cell imaging, and
      supported by numerical modeling suggests a novel concept: the normal rhythmic
      heart beat is governed by the tight integration of both intracellular Ca(2+) and
      membrane clocks. In pacemaker cells the intracellular Ca(2+) clock is manifested
      by spontaneous, rhythmic submembrane local Ca(2+) releases from SR, which are
      tightly controlled by a high degree of basal and reserve PKA-dependent protein
      phosphorylation. The Ca(2+) releases rhythmically activate Na(+)/Ca(2+) exchange
      inward currents that ignite action potentials, whose shape and ion fluxes are
      tuned by the membrane clock which, in turn, sustains operation of the
      intracellular Ca(2+) clock. The idea that spontaneous SR Ca(2+) releases initiate
      and regulate normal automaticity provides the key that reunites pacemaker and
      ventricular cell research, thus evolving a general theory of the initiation and
      strength of the heartbeat.

PMID- 16799256
TI  - Tissue angiotensin II generating system by angiotensin-converting enzyme and
      chymase.
AB  - It had been believed that angiotensin II (Ang II) was produced by the renin
      angiotensin system (RAS), which was established in the 1950's. After a while,
      people realized that the multiple functions of Ang II could not be explained by
      the conventional RAS. We have tried to determine the existence of the tissue Ang
      II generating system. At first, we found that vascular angiotensin-converting
      enzyme (ACE) was increased to generate local Ang II in the vessels of
      hypertension and was enhanced in lipid-loaded atherosclerosis, to respond to ACE
      inhibitor or Ang II antagonist (ARB). In both cases, Ang II production in vessels
      was independent from the systemic RAS that was estimated by the plasma renin
      activity. On the way to clarifying the roles of the vascular ACE, we noticed that
      vascular Ang II production was not completely suppressed by ACE inhibitor alone.
      This evidence led us to discover different types of chymase as a new Ang II
      producing enzyme. Now, we have obtained a strategy to distinguish the Ang II one
      by one, that is, circulating RAS derived, tissue ACE derived, and chymase
      derived. It is essential to understand not only the intracellular mechanisms of
      Ang II but also the process of Ang II productions in each disease to show
      accurate indications of the effectiveness of ACE inhibitor, ARB, and chymase
      inhibitor.

PMID- 16799257
TI  - Organic anion transporter family: current knowledge.
AB  - Organic anion transporters (OATs) play an essential role in the elimination of
      numerous endogenous and exogenous organic anions from the body. The renal OATs
      contribute to the excretion of many drugs and their metabolites that are
      important in clinical medicine. Several families of multispecific organic anion
      and cation transporters, including OAT family transporters, have recently been
      identified by molecular cloning. The OAT family consists of six isoforms (OAT1 -
      4, URAT1, and rodent Oat5) and they are all expressed in the kidney, while some
      are also expressed in the liver, brain, and placenta. The OAT family represents
      mainly the renal secretory and reabsorptive pathway for organic anions and is
      also involved in the distribution of organic anions in the body, drug-drug
      interactions, and toxicity of anionic substances such as nephrotoxic drugs and
      uremic toxins. In this review, current knowledge of and recent progress in the
      understanding of several aspects of OAT family members are discussed.

PMID- 16799258
TI  - Molecular pathopharmacology of 5-HT2C receptors and the RNA editing in the brain.
AB  - Among the 14 kinds of serotonin (5-hydroxytryptamine, 5-HT) receptor subtypes (5
      HTR), 5-HT(2C) receptor (5-HT2CR) has been intensively investigated because of
      its physiologically and pathophysiologically important role in the brain. 5-HT2CR
      has been suggested to be involved in depressive disorders based on findings from
      pharmacological/neurochemical/behavioral studies using autopsy preparations of
      humans suffering from depression, animal models of depression, and animals
      treated with antidepressant drugs. Recently the editing of 5-HT2CR mRNA has been
      reported to participate in the pathogenesis of depressive disease. The RNA
      editing of 5-HT2CR induced by the presumable alteration of deaminase during a
      pathological state in depression causes changes of a base to another base (e.g.,
      adenosine to guanosine, cytidine to uracil (thymidine)), followed by changes in
      amino acids constituting the second intracellular transmembrane loop that couples
      G proteins. Thus 5-HT2CR receptor-mediated signal transduction is changed. In the
      present review, the pathopharmacological significance of 5-HT2CR in special
      reference to RNA editing of receptors is reviewed and discussed from the aspect
      of development of novel therapeutics for depression.

PMID- 16799260
TI  - How do acupuncture and moxibustion act? - Focusing on the progress in Japanese
      acupuncture research -.
AB  - The mechanisms of action of acupuncture and moxibustion as reported by Japanese
      researchers are reviewed. The endogenous opioid-mediated mechanisms of
      electroacupuncture (EA) as used in China are well understood, but these are only
      one component of all mechanisms of acupuncture. These studies emphasize the
      similarity of the analgesic action of EA to various sensory inputs to the pain
      inhibition mechanisms. In Japanese acupuncture therapy, careful detection of the
      acupuncture points and fine needling technique with comfortable subjective
      sensation are considered important. The role of polymodal receptors (PMR) has
      been stressed based on the facts that PMRs are responsive to both acupuncture and
      moxibustion stimuli, thermal sensitivity is essential in moxibustion therapy, and
      the characteristics of acupuncture points and trigger points are similar to those
      of sensitized PMRs. Acupuncture and moxibustion are also known to affect neurons
      in the brain reward systems and blood flow in skin, muscle, and nerve. Axon
      reflexes mediated by PMRs might be a possible mechanism for the immediate action
      of acupuncture and moxibustion. Reports on the curative effects of acupuncture on
      various digestive and urological disorders are also reviewed briefly.

PMID- 16799259
TI  - Molecular mechanism of neuronal plasticity: induction and maintenance of long
      term potentiation in the hippocampus.
AB  - Recent studies have demonstrated that activation of enzymes can be observed in
      living cells in response to stimulation with neurotransmitters, hormones, growth
      factors, and so forth. Thus, the activation of enzymes was shown to be closely
      related to the dynamic states of various cell functions. The development of new
      experimental methodologies has enabled researchers to study the molecular basis
      of neuronal plasticity in living cells. In 1973, Bliss and his associates
      identified the phenomena of long-term potentiation (LTP). Since it was thought to
      be a model for neuronal plasticity such as learning and memory, its molecular
      mechanism has been extensively investigated. The mechanism was found to involve a
      signal transduction cascade that includes release of glutamate, activation of the
      NMDA glutamate receptors, Ca(2+) entry, and activations of Ca(2+)/calmodulin
      dependent protein kinases (CaM kinases) II and IV and mitogen-activated protein
      kinase (MAPK). Consequently, AMPA glutamate receptors were activated by
      phosphorylation by CaM kinase II, resulting in an increase of Ca(2+) entry into
      postsynaptic neurons. Furthermore, activation of CaM kinase IV and MAPK increased
      phosphorylation of CREB (cyclic AMP response element binding protein) and
      expression of c-Fos by stimulation of gene expression. These results suggest that
      LTP induction and maintenance would be models of short- and long-term memory,
      respectively.

PMID- 16799261
TI  - A new frontier in epilepsy: novel antiepileptogenic drugs.
AB  - Epilepsy is a hetergenous syndrome characterized by recurrently and repeatedly
      occurring seizures. Although able to inhibit the epileptic seizures, the
      currently available antiepileptic drugs (AEDs) have no effects on
      epileptogenesis. Such AEDs should be classified as drugs against ictogenesis,
      which are transient events in ion and/or receptor-gated channels related with
      triggering to evoke seizures. Epileptogenesis involves long-term and
      histological/biochemical/physiological alterations formed in brain structures
      over a long period, ranging from months to years. This review focuses on the
      effects of AEDs on epileptogenesis and novel candidates of antiepileptogenic
      drugs using a genetically defined epilepsy model animal, the spontaneous
      epileptic rat (SER).

PMID- 16799262
TI  - Water channels and zymogen granules in salivary glands.
AB  - Salivary secretion occurs in response to stimulation by neurotransmitters
      released from autonomic nerve endings. The molecular mechanisms underlying the
      secretion of water, a main component of saliva, from salivary glands are not
      known; the plasma membrane is a major barrier to water transport. A 28-kDa
      integral membrane protein, distributed in highly water-permeable tissues, was
      identified as a water channel protein, aquaporin (AQP). Thirteen AQPs (AQP0 -
      AQP12) have been identified in mammals. AQP5 is localized in lipid rafts under
      unstimulated conditions and translocates to the apical plasma membrane in rat
      parotid glands upon stimulation by muscarinic agonists. The importance of
      increases in intracellular calcium concentration [Ca(2+)](i) and the nitric oxide
      synthase and protein kinase G signaling pathway in the translocation of AQP5 is
      reviewed in section I. Signals generated by the activation of Ca(2+) mobilizing
      receptors simultaneously trigger and regulate exocytosis. Zymogen granule
      exocytosis occurs under the control of essential process, stimulus-secretion
      coupling, in salivary glands. Ca(2+) signaling is a principal signal in both
      protein and water secretion from salivary glands induced by cholinergic
      stimulation. On the other hand, the cyclic adenosine monophosphate (cAMP)/cAMP
      dependent protein kinase system has a major role in zymogen granule exocytosis
      without significant increases in [Ca(2+)](i). In section II, the mechanisms
      underlying the control of salivary protein secretion and its dysfunction are
      reviewed.

PMID- 16799263
TI  - Signal transduction and Ca2+ signaling in intact myocardium.
AB  - The experimental procedures to simultaneously detect contractile activity and
      Ca(2+) transients by means of the Ca(2+) sensitive bioluminescent protein
      aequorin in multicellular preparations, and the fluorescent dye indo-1 in single
      myocytes, provide powerful tools to differentiate the regulatory mechanisms of
      intrinsic and external inotropic interventions in intact cardiac muscle. The
      regulatory process of cardiac excitation-contraction coupling is classified into
      three categories; upstream (Ca(2+) mobilization), central (Ca(2+) binding to
      troponin C), and/or downstream (thin filament regulation of troponin C property
      or crossbridge cycling and crossbridge cycling activity itself) mechanisms. While
      a marked increase in contractile activity by the Frank-Starling mechanism is
      associated with only a small alteration in Ca(2+) transients (downstream
      mechanism), the force-frequency relationship is primarily due to a frequency
      dependent increase of Ca(2+) transients (upstream mechanism) in mammalian
      ventricular myocardium. The characteristics of regulation induced by beta- and
      alpha-adrenoceptor stimulation are very different between the two mechanisms: the
      former is associated with a pronounced facilitation of an upstream mechanism,
      whereas the latter is primarily due to modulation of central and/or downstream
      mechanisms. alpha-Adrenoceptor-mediated contractile regulation is mimicked by
      endothelin ET(A)- and angiotensin II AT(1)-receptor stimulation. Acidosis
      markedly suppresses the regulation induced by Ca(2+) mobilizers, but certain
      Ca(2+) sensitizers are able to induce the positive inotropic effect with central
      and/or downstream mechanisms even under pathophysiological conditions.

PMID- 16799264
TI  - Calcium signals for egg activation in mammals.
AB  - A dramatic increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) occurs in
      eggs at fertilization common to all animal species examined to date, and this
      serves as a pivotal signal for egg activation characterized by resumption of
      meiotic cell division and formation of the pronuclei. In mammalian eggs,
      repetitive [Ca(2+)](i) rises (Ca(2+) oscillations) each of which accompanies a
      propagating wave across the egg occur due to release of Ca(2+) from the
      endoplasmic reticulum mainly through type 1 inositol 1,4,5-trisphosphate (IP(3))
      receptor. Ca(2+) oscillations are induced by a cytosolic sperm factor driven into
      the egg cytoplasm upon sperm-egg fusion. A current strong candidate of the sperm
      factor is a novel sperm-specific isozyme of phospholipase C (IP(3)-producing
      enzyme), PLCzeta. Recent extensive research has reveled characteristics of
      PLCzeta such as the Ca(2+) oscillation-inducing activity after injection of
      PLCzeta-encoding RNA or recombinant PLCzeta into mouse eggs, extremely high
      Ca(2+)-sensitivity of the enzymatic activity in vitro, and nuclear translocation
      ability possibly related to cell-cycle-dependent regulation of Ca(2+)
      oscillations. [Ca(2+)](i) rises cause successive activation of calmodulin
      dependent kinase II and E3 ubiquitin ligase, lead to proteolysis of ubiquitinated
      cyclin B1 and inactivation of metaphase-promoting factor (Cdk1/cyclin B1
      complex), and result in the release of eggs from meiotic arrest.

PMID- 16799265
TI  - Effect of Pueraria mirifica on the sexual skin coloration of aged menopausal
      cynomolgus monkeys.
AB  - To investigate the estrogenic effect of Pueraria mirifica (PM), a Thai herbal
      plant that contains many phytoestrogens, sexual skin coloration was studied in
      cynomolgus monkeys. Aged menopausal monkeys were divided into three groups. Each
      group (n=3) was fed 10, 100, or 1,000 mg of PM daily. The treatment schedule was
      divided into three periods, a 30-day pre-treatment period, 90-day treatment
      period, and 60-day post-treatment period. The results show that the sexual skin
      exhibited reddish coloration within 24 h after PM-treatment and remained this way
      for the first half of the PM-feeding period. The changes in sexual skin
      coloration were not dose-dependent. The present results indicate that PM had
      estrogenic action by increasing reddish sexual skin coloration in aged menopausal
      monkeys.

PMID- 16799266
TI  - Simple prediction of the survival of follicles in cryopreserved human ovarian
      tissue.
AB  - This study examines the possible predictive value of the LIVE/DEAD fluorescence
      viability assay for evaluation of survival of cryopreserved human ovarian tissue.
      Ovarian tissue from ten patients was examined by LIVE/DEAD viability staining
      before and after cryopreservation and after freezing in a -20 C freezer (negative
      control). After cryopreservation with a slow freezing protocol and cryoprotectant
      the LIVE/DEAD assay showed 86% viable follicles (an intact oocyte and at least
      more than 50% of the granulosa cells alive), whereas after freezing at -20 C the
      survival rate was 67%. The healthy follicular loss after cryopreservation was 4%,
      whereas with freezing at -20 C, it was 25%. Although this assay overestimates the
      survival rate of cryopreserved primordial follicles, if the LIVE/DEAD assay
      yields greater than approximately 85% viable follicles, it can be assumed that
      the follicles in the cryopreserved tissue have maintained their developmental
      potential and that the tissue is suitable for retransplantation.

PMID- 16799267
TI  - Epidural steroid injection for lumbosacral radiculopathy.

PMID- 16799268
TI  - CT findings of atypical adenomatous hyperplasia in the lung.
AB  - OBJECTIVE: The aim of this study was to analyze the computed tomographic (CT)
      findings of atypical adenomatous hyperplasia (AAH) in the lung. MATERIALS AND
      METHODS: The CT findings of AAHs in eight patients were retrospectively reviewed.
      The CT findings of each AAH lesion were evaluated for multiplicity, location,
      shape, size and internal density of the lesion, the interface between the normal
      lung and the lesion, the internal features within the lesion and any change of
      the lesion on the follow-up CT scans (range: 33 to 540 days; average: 145.3
      days). RESULTS: The eight patients consisted of three men and five women (age
      range: 43-71 years). Six of eight patients were asymptomatic. Four of them (50%)
      had synchronous malignancies in the lung: adenocarcinoma of the lung (n = 3), and
      metastatic squamous cell carcinoma from the uterus (n = 1). We could identify and
      evaluate eleven AAH nodules in seven patients on the CT scans. Three patients had
      multiple AAHs. Seven of the 11 lesions (64%) were located in the upper lobe. All
      the AAHs showed a well-defined oval or round shape and pure ground-glass opacity
      (GGO) without any solid component (size: 3.9x3 mm to 19x17 mm; internal
      attenuation: -467 to -785 HU). All the AAHs showed no change of their size and
      internal density on the follow-up CT scans. CONCLUSION: Atypical adenomatous
      hyperplasia is often associated with malignancy. This tumor is shown on CT as
      persistent well-defined oval or round nodular GGOs without solid components, and
      it does not change on the follow-up CT.

PMID- 16799269
TI  - Added value of coronal reformations for duty radiologists and for referring
      physicians or surgeons in the CT diagnosis of acute appendicitis.
AB  - OBJECTIVE: To assess the added value of coronal reformation for radiologists and
      for referring physicians or surgeons in the CT diagnosis of acute appendicitis.
      MATERIALS AND METHODS: Contrast-enhanced CT was performed using 16-detector-row
      scanners in 110 patients, 46 of whom had appendicitis. Transverse (5-mm
      thickness, 4-mm increment), coronal (5-mm thickness, 4-mm increment), and
      combined transverse and coronal sections were interpreted by four radiologists,
      two surgeons and two emergency physicians. The area under the receiver operating
      characteristic curve (Az value), sensitivity, specificity (McNemar test),
      diagnostic confidence and appendiceal visualization (Wilcoxon signed rank test)
      were compared. RESULTS: For radiologists, the additional coronal sections tended
      to increase the Az value (0.972 vs. 0.986, p = 0.076) and pooled sensitivity (92%
      [95% CI:88, 96] vs. 96% [93, 99]), and enhanced appendiceal visualization in true
      positive cases (p = 0.031). For non-radiologists, no such enhancement was
      observed, and the confidence for excluding acute appendicitis declined (p =
      0.013). Coronal sections alone were inferior to transverse sections for
      diagnostic confidence as well as appendiceal visualization for each reader group
      studied (p < 0.05). CONCLUSION: The added value of coronal reformation is more
      apparent for radiologists compared to referring physicians or surgeons in the CT
      diagnosis of acute appendicitis.

PMID- 16799270
TI  - Radio frequency ablation in the rabbit lung using wet electrodes: comparison of
      monopolar and dual bipolar electrode mode.
AB  - OBJECTIVE: To compare the effect of radio frequency ablation (RFA) on the
      dimensions of radio frequency coagulation necrosis in a rabbit lung using a wet
      electrode in monopolar mode with that in dual electrode bipolar mode at different
      infusion rates (15 mm/hr versus 30 ml/hr) and saline concentrations (0.9% normal
      versus 5.8% hypertonic saline). MATERIALS AND METHODS: Fifty ablation zones (one
      ablation zone in each rabbit) were produced in 50 rabbits using one or two 16
      gauge wet electrodes with a 1-cm active tip. The RFA system used in the monopolar
      and dual electrode wet bipolar RFA consisted of a 375-kHz generator (Elektrotom
      HiTT 106, Berchtold, Medizinelektronik, Germany). The power used was 30 watts and
      the exposure time was 5 minutes. The rabbits were assigned to one of five groups.
      Group A (n = 10) was infused with 0.9% NaCl used at a rate of 30 ml/hr in a
      monopolar mode. Groups B (n = 10) and C (n = 10) were infused with 0.9% NaCl at a
      rate of 15 and 30 ml/hr, respectively in dual electrode bipolar mode; groups D (n
      = 10) and E (n = 10) were infused with 5.8% NaCl at a rate of 15 and 30 ml/hr,
      respectively in a dual electrode bipolar mode. The dimensions of the ablation
      zones in the gross specimens from the groups were compared using one-way analysis
      of variance by means of the Scheffe test (post-hoc testing). RESULTS: The mean
      largest diameter of the ablation zones was larger in dual electrode bipolar mode
      (30.9+/-4.4 mm) than in monopolar mode (22.5+/-3.5 mm). The mean smallest
      diameter of the ablation zones was larger in dual electrode bipolar mode (22.3+/
      2.5 mm) than in monopolar mode (19.5+/-3.5 mm). There were significant
      differences in the largest and smallest dimension between the monopolar (group A)
      and dual electrode wet bipolar mode (groups B-E). In dual electrode bipolar mode,
      the mean largest diameter of the ablation zones was larger at an infusion rate of
      15 ml/hr (34.2+/-4.0 mm) than at 30 ml/hr (27.6+/-0.1 mm), and the mean smallest
      diameter of the ablation zones was larger at an infusion rate of 15 ml/hr (27.2+/
      7.5 mm) than at an infusion rate of 30 ml/hr (24+/-2.9 mm). CONCLUSION: Using a
      wet electrode, dual electrode bipolar RFA can create a larger ablation zone more
      efficiently than monopolar RFA.

PMID- 16799271
TI  - Hepatic radiofrequency ablation using multiple probes: ex vivo and in vivo
      comparative studies of monopolar versus multipolar modes.
AB  - OBJECTIVE: We wanted to compare the efficiency of multipolar radiofrequency
      ablation (RFA) using three perfused-cooled electrodes with multiple overlapping
      and simultaneous monopolar techniques for creating an ablation zone in ex vivo
      bovine livers and in in vivo porcine livers. MATERIALS AND METHODS: In the ex
      vivo experiments, we used a 200 W generator (Valleylab, CC-3 model) and three
      perfused-cooled electrodes or internally cooled electrodes to create 30
      coagulation zones by performing consecutive monopolar RFA (group A, n = 10),
      simultaneous monopolar RFA (group B, n = 10) or multipolar RFA (group C, n = 10)
      in explanted bovine livers. In the consecutive mode, three ablation spheres were
      created by sequentially applying 150 watts radiofrequency (RF) energy to the
      internally cooled electrodes for 12 minutes each for a total of 36 minutes. In
      the simultaneous monopolar and multipolar modes, RF energy was concurrently
      applied to the three perfused-cooled electrodes for 20 minutes at 150 watt with
      instillation of 6% hypertonic saline at 2 mL/min. During RFA, we measured the
      temperatures of the treated area at its center. The changes in impedance, the
      current and liver temperature during RFA, as well as the dimensions of the
      thermal ablation zones, were compared among the three groups. In the in vivo
      experiments, three coagulations were created by performing multipolar RFA in a
      pig via laparotomy with using same parameter as the ex vivo study. RESULTS: In
      the ex vivo experiments, the impedance was gradually decreased during the RFA in
      groups B and C, but in group A, the impedance was increased during RFA and this
      induced activation by the pulsed RF technique. In groups A, B and C, the mean
      final-temperature values were 80+/-10 degrees C, 69+/-18 degrees C and 79+/-12
      degrees C, respectively (p < 0.05). The multipolar mode created a larger volume
      of ablation than did the other modes: 37.6+/-4.0 cm3 (group A); 44.9+/-12.7 cm3
      (group B); and 78.9+/-6.9 cm3 (group C) (p < 0.05). In the in vivo experiment,
      the pig well tolerated the RFA procedure and no major complications occurred
      during the 4 days of the follow-up period. The mean volume of coagulations
      produced by multipolar RFA in the pig liver was 60.5+/-17.9 cm3. CONCLUSION: For
      the multiple probe RFA, the multipolar mode with hypertonic saline instillation
      was more efficient in generating larger areas of thermal ablation than either the
      consecutive or simultaneous monopolar modes.

PMID- 16799272
TI  - Metallic stent placement in hemodialysis graft patients after insufficient
      balloon dilation.
AB  - OBJECTIVE: We wanted to report our experience of metallic stent placement after
      insufficient balloon dilation in graft hemodialysis patients. MATERIALS AND
      METHODS: Twenty-three patients (13 loop grafts in the forearm and 10 straight
      grafts in the upper arm) underwent metallic stent placement due to insufficient
      flow after urokinase thrombolysis and balloon dilation. The indications for
      metallic stent deployment included 1) recoil and/or kinked venous stenosis in 21
      patients (venous anastomosis: 17 patients, peripheral outflow vein: four
      patients); and 2) major vascular rupture in two patients. Metallic stents 8-10 mm
      in diameter and 40-80 mm in length were used. Of them, eight stents were deployed
      across the elbow crease. Access patency was determined by clinical follow-up and
      the overall rates were calculated by Kaplan-Meier survival analysis. RESULTS: No
      procedure-related complications (stent fracture or central migration) were
      encountered except for a delayed Wallstent shortening/migration at the venous
      anastomosis, which resulted in early access failure. The overall primary and
      secondary patency rates (+/-standard error) of all the vascular accesses in our
      23 patients at 3, 6, 12 and 24 months were 69%+/-9 and 88%+/-6, 41%+/-10 and
      88%+/-6, 30%+/-10 and 77%+/-10, and 12%+/-8 and 61%+/-13, respectively. For the
      forearm and upper-arm grafts, the primary and secondary patency rates were 51%+/
      16 and 86%+/-13 vs 45%+/-15 and 73%+/-13 at 6 months, and 25%+/-15 and 71%+/-17
      vs 23%+/-17 and 73%+/-13 at 12 months (p = .346 and .224), respectively.
      CONCLUSION: Metallic stent placement is a safe and effective means for treating
      peripheral venous lesions in dialysis graft patients after insufficient balloon
      dilation. No statistically difference in the patency rates between the forearm
      and upper-arm patient groups was seen.

PMID- 16799273
TI  - Safety and effectiveness of moderate sedation for radiologic non-vascular
      intervention.
AB  - OBJECTIVE: The purpose of this study was to prospectively characterize the safety
      and effectiveness of moderate sedation/analgesia for performing radiologic non
      vascular abdominal intervention. MATERIALS AND METHODS: During a 3-month period,
      a total of 63 adult patients with a mean age of 64 years (range: 27-82) underwent
      moderate sedation for 72 radiologic non-vascular interventional procedures. A
      combination of fentanyl citrate and midazolam hydrochloride, based on the
      patient's body weight, was intravenously administered until the patient was
      drowsy and tranquil. The adverse events associated with this moderate sedation
      were assessed. The visual analog scale format was used to measure the subjective
      feelings of the patient's pre-procedural anxiety and intraprocedural pain.
      RESULTS: The mean total dose per kilogram of body weight of fentanyl used in PTBD
      was 1.148 microg, it was 1.157 microg for PTGBD, 1 microg for AD, 1 microg for
      PCN, 1.641 microg for TDC, 1 microg for DJS, 2 microg for BS, 1 microg for GS and
      2 microg for RFA. The mean total dose per kilogram of body weight of midazolam
      was 0.035 mg in PTBD, PTGBD, AD, PCN, DJS, GS and RFA, 0.039 mg in TDC, and 0.043
      mg in BS. A temporary reduction of systolic blood pressure to less than 80 mmHg
      was observed during 5 procedures (6.9%), whereas a temporary elevation of
      systolic blood pressure above 150 mmHg was observed during 10 procedures (13.8%).
      A reduction of arterial oxygen saturation to less than 90% was observed during 14
      procedures (19.4%). None of the patients required pharmacologic reversal agents
      or cardiopulmonary resuscitation. The mean anxiety score recorded before all
      procedures was 5.2 (distressing). The mean pain score during the procedure, which
      was recorded after all procedures, was 2.9 (mild). CONCLUSION: Moderate sedation
      allows performance of safe and effective radiologic non-vascular intervention,
      and it is also easy for an interventional radiologist to use. The patients should
      be continuously monitored to check their vital signs and arterial oxygen
      saturation during the procedures.

PMID- 16799274
TI  - Subintimal angioplasty in the treatment of chronic lower limb ischemia.
AB  - OBJECTIVE: To present our experience with subintimal angioplasty (SA) for
      treatment of chronic lower limb ischemia (CLLI) and to assess its effectiveness
      and durability. MATERIALS AND METHODS: From April 2003 through June 2005, we
      treated 40 limbs in 36 patients with CLLI by SA. Balloons with or without
      secondary stent placement appropriate in size to the occluded arteries were used
      for SA of all lesions, except for iliac lesions where primary stent placement was
      done. The patients were followed for 1-23 months by clinical examination and
      color Doppler ultrasound and/or CT angiography. Technical results and outcomes
      were retrospectively evaluated. The presence of a steep learning curve for
      performance of SA was also evaluated. Primary and secondary patencies were
      determined using Kaplan-Meier analysis. RESULTS: Technical success was achieved
      in 32 (80%) of 40 limbs. There was no statistical difference between technical
      success rates of 75% (18/24) during the first year and 88% (14/16) thereafter.
      There were four complications (10%) in 40 procedures; two arterial perforations,
      one pseudoaneurysm at the puncture site, and one delayed hematoma at the SA site.
      Excluding initial technical failures, the primary patency rates at six and 12
      months were 68% and 55%, respectively. Secondary patency rates at six and 12
      months were 73% and 59%, respectively. CONCLUSION: Subintimal angioplasty can be
      accomplished with a high technical success rate. It should be attempted in
      patients with CLLI as an alternative to more extended surgery, or when surgical
      treatment is not recommended due to comorbidity or an unfavorable disease
      pattern.

PMID- 16799275
TI  - Transforaminal epidural steroid injection for lumbosacral radiculopathy:
      preganglionic versus conventional approach.
AB  - OBJECTIVE: The present study was undertaken to evaluate the effectiveness of
      transforaminal epidural steroid injection (TFESI) with using a preganglionic
      approach for treating lumbar radiculopathy when the nerve root compression was
      located at the level of the supra-adjacent intervertebral disc. MATERIALS AND
      METHODS: The medical records of the patients who received conventional TFESI at
      our department from June 2003 to May 2004 were retrospectively reviewed. TFESI
      was performed in a total of 13 cases at the level of the exiting nerve root, in
      which the nerve root compression was at the level of the supra-adjacent
      intervertebral disc (the conventional TFESI group). Since June 2004, we have
      performed TFESI with using a preganglionic approach at the level of the supra
      adjacent intervertebral disc (for example, at the neural foramen of L4-5 for the
      L5 nerve root) if the nerve root compression was at the level of the supra
      adjacent intervertebral disc. Using the inclusion criteria described above, 20 of
      these patients were also consecutively enrolled in our study (the preganglionic
      TFESI group). The treatment outcome was assessed using a 5-point patient
      satisfaction scale and by using a VAS (visual assessment scale). A successful
      outcome required a patient satisfaction scale score of 3 (very good) or 4
      (excellent), and a reduction on the VAS score of > 50% two weeks after performing
      TFESI. Logistic regression analysis was also performed. RESULTS: Of the 13
      patients in the conventional TFESI group, nine showed satisfactory improvement
      two weeks after TFESI (69.2%). However, in the preganglionic TFESI group, 18 of
      the 20 patients (90%) showed satisfactory improvement. The difference between the
      two approaches in terms of TFESI effectiveness was of borderline significance (p
      = 0.056; odds ratio: 10.483). CONCLUSION: We conclude that preganglionic TFESI
      has the better therapeutic effect on radiculopathy caused by nerve root
      compression at the level of the supra-adjacent disc than does conventional TFESI,
      and the difference between the two treatments had borderline statistical
      significance.

PMID- 16799276
TI  - Parenchymal neurocutaneous melanosis in association with intraventricular dermoid
      and Dandy-Walker variant: a case report.
AB  - Neurocutaneous melanosis (NCM) is a rare congenital disease that is characterized
      by the presence of large or multiple congenital melanocytic nevi and melanotic
      lesions of the central nervous system. We report here on the CT and MR imaging
      findings of an unusual case of NCM that was associated with intraventricular
      dermoid and Dandy-Walker malformation.

PMID- 16799277
TI  - Sonographic detection of intrathyroidal branchial cleft cyst: a case report.
AB  - We report here on an extremely rare case of an intrathyroidal branchial cleft
      cyst. Intrathyroidal branchial cleft cyst is rare disease entity and it has
      nonspecific findings on sonography, so the diagnosis of the lesion is very
      difficult. However, during aspiration, if pus-like materials are aspirated from a
      thyroid cyst, we should consider the possibility of intrathyroidal branchial
      cleft cyst in the differential diagnosis.

PMID- 16799278
TI  - Increasing the aggregate supply of physicians.

PMID- 16799279
TI  - Residents' perceptions over time of pharmaceutical industry interactions and
      gifts and the effect of an educational intervention.
AB  - PURPOSE: To describe change in residents' attitudes toward gifts from and
      interactions with industry and to measure the effects of a formal educational
      workshop on changes in perceptions. METHOD: At the University of Chicago, 118
      internal medicine residents completed an observational survey and took part in a
      controlled intervention across three years (2001-2004) of residency. Four cohorts
      of residents completing the program in 2004-2007 participated. The intervention
      was an interactive educational workshop, including reviews of literature and
      guidelines, and three videos demonstrating routine resident interactions with
      pharmaceutical representatives. Residents graduating in 2005 were the
      intervention group and residents graduating in 2004 the comparison group.
      Analysis of variance and linear regression models were used to determine the
      relationship between variables. RESULTS: Residents perceived "lunch sponsored at
      noon conference" and "pharmaceutical representative brief talk at noon
      conference" as increasingly appropriate over their training period (p < .02).
      Residents perceived "pens, notepads, pocket antibiotic guides" as increasingly
      appropriate and "tickets to sporting events," "round of golf," and
      "travel/registration for national conference" as increasingly inappropriate (p <
      .05). The intervention group was more likely to rate only one item, "lunch at
      noon conference," as less appropriate (p = .042). CONCLUSIONS: Residents'
      perceptions toward industry gifts and interactions changed modestly during their
      training to reflect institutional policy. "Appropriate" gifts of minimal value
      were generally perceived as increasingly appropriate, whereas "inappropriate"
      gifts were perceived as increasingly inappropriate over time. An educational
      workshop alone may not significantly alter residents' perceptions toward industry
      without the implementation of broad and consistent institutional policy.

PMID- 16799280
TI  - Performance of medical students in a nontraditional rural clinical program, 1998
      99 through 2003-04.
AB  - PURPOSE: To compare knowledge acquisition as measured by test scores for students
      in nontraditional clinical clerkships to scores for students in traditional urban
      hospital-based clerkships. Interdisciplinary and continuity-of-care clerkships in
      rural areas are the focus of the study. METHOD: All the students' Medical College
      Admission Test (MCAT) scores, National Board of Medical Examiners (NBME) subject
      exam scores, and United States Medical Licensing Examination (USMLE) Step 1 and
      Step 2 scores over a six-year period, 1998-99 to 2003-04, were compared for third
      year students in nontraditional and traditional clerkships at the University of
      North Dakota School of Medicine and Health Sciences. Cohorts were 29 students in
      our Rural Opportunities in Medical Education (ROME) program and 296 students in
      traditional third-year clerkships. NBME subject exam scores were those in
      pediatrics, internal medicine, surgery, and obstetrics and gynecology. The exam
      used for family medicine is not standardized to national standards, but
      controlled within the Department of Family Medicine. MCAT and USMLE Step 1 scores
      were used as a means of controlling for prior academic achievement and ability.
      RESULTS: There were no significant differences (p > or = .05) in MCAT scores,
      Step 1 scores, subject exam scores, or Step 2 scores between the two groups. In
      contrast, students from ROME scored higher (p < or = .05) on the internal
      medicine clinical preceptor assessments than did students from the traditional
      track. CONCLUSIONS: These findings suggest that students in remote, rural,
      longitudinal, integrated learning environments can attain fund-of-knowledge
      scores comparable to the scores of students in traditional clerkships, and may,
      as in this study, receive higher ratings for clinical proficiency.

PMID- 16799281
TI  - Implementing achievable benchmarks in preventive health: a controlled trial in
      residency education.
AB  - PURPOSE: To evaluate the Preventive Health Achievable Benchmarks Curriculum, a
      multifaceted improvement intervention that included an objective, practice-based
      performance evaluation of internal medicine and pediatric residents' delivery of
      preventive services. METHOD: The authors conducted a nonrandomized experiment of
      intervention versus control group residents with baseline and follow-up of
      performance audited for 2001-2004. All 130 internal medicine and 78 pediatric
      residents at two continuity clinics at the University of Alabama School of
      Medicine, Birmingham, participated. Performance of preventive care was assessed
      by structured chart review. The multifaceted feedback curriculum included
      individualized performance feedback, academic detailing by faculty, and
      collective didactic sessions. The main outcome was difference in receipt of
      preventive care for patients seen by intervention and control residents,
      comparing baseline and follow-up. RESULTS: Charts were reviewed for 3,958
      patients. Receipt of preventive care increased for patients of intervention
      residents, but not for patients of control residents. For the intervention group,
      significant increases occurred for five of six indicators in internal medicine:
      smoking screening, quit smoking advice, colon cancer screening, pneumonia
      vaccine, and lipid screening; and four of six in pediatrics: parental quit
      smoking advice, car seats, car restraints, and eye alignment (p < .05 for all).
      For control residents, no consistent improvements were seen. There was greater
      improvement for intervention than for control residents for four of six
      indicators in internal medicine, and two of six in pediatrics. CONCLUSIONS: Using
      a multifaceted feedback curriculum, the authors taught residents about the care
      they provide and improved documented patient care.

PMID- 16799282
TI  - Problem-based learning outcomes: ten years of experience at the University of
      Missouri-Columbia School of Medicine.
AB  - PURPOSE: To add to a previous publication from the University of Missouri
      Columbia School of Medicine (UMCSOM) on students' improvement in United States
      Medical Licensing Examination (USMLE) Step 1 and Step 2 scores after the
      implementation of a problem-based learning (PBL) curriculum by studying the
      performance of ten PBL class cohorts at the UMCSOM. METHOD: Characteristics of
      graduating classes matriculating in both traditional and PBL curricula, 1993
      2006, were compared for Medical College Admission Test component scores,
      undergraduate grade point averages, performance on the USMLE Step 1 and Step 2
      exams, faculty contact hours, and residency directors' evaluations of UMCSOM
      graduates' performance in the first year of residency. RESULTS: Mean scores of
      six of the ten comparisons for USMLE Step 1 and six of nine comparisons for USMLE
      Step 2 are significantly higher (p < .01) for UMCSOM PBL students than for first
      time examinees nationally. These differences cannot be accounted for by
      preselection of academically advantaged students, increased time on task, or
      reduced class size. Gains in performance continue into residency, as evidenced by
      program directors' perceptions of superior performance of UMCSOM PBL graduates.
      CONCLUSIONS: The PBL curricular changes implemented with the graduating class of
      1997 resulted in higher performances on USMLEs and improved evaluations from
      residency program directors. These changes better prepare graduates with
      knowledge and skills needed to practice within a complex health care system.
      Outcomes reported here support the investment of financial and human resources in
      our PBL curriculum.

PMID- 16799284
TI  - The relationship of relationships.

PMID- 16799283
TI  - Bringing ethics education to the clinical years: ward ethics sessions at the
      University of Washington.
AB  - PURPOSE: Although most medical schools teach medical ethics during preclinical
      years, incorporating these ethics into clinical training remains challenging.
      During clinical rotations, students' professional behaviors and attitudes are
      profoundly affected. This project was intended to develop an educational
      intervention to incorporate medical ethics training as a part of students'
      professional development within the context of clinical training. METHOD: "Ward
      Ethics" is a series of peer discussions guided by clinical faculty mentors
      trained in fostering issue identification and strategy development. The sessions
      described here were conducted during medicine and surgery rotations for third
      year medical students at the University of Washington School of Medicine from
      1998 to 2003. Thirty clinical faculty participated as facilitators. Written
      evaluations were collected from students and faculty at each session, and faculty
      interviews were conducted in 2001. RESULTS: The data reported are from 24
      sessions and 15 faculty interviews from 1999 to 2001. The topics were consistent
      with prior reports of ethical issues that students encountered. Students reported
      a variety of learned strategies such as knowing how and when to speak up and
      transitioning from prioritizing evaluations to focusing on patient care,
      resulting in their feeling more confident. Faculty reported noticing positive
      results to their professional development as well. CONCLUSIONS: Medical students
      in the clinical years face ethically challenging situations. Some circumstances,
      if left unexamined, may erode students' abilities to maintain and develop
      appropriate professional behaviors. Students participating in this activity
      agreed that it served as a way to fight isolation, share stories, and exchange
      ideas for future problem solving.

PMID- 16799285
TI  - Educational technology infrastructure and services in North American medical
      schools.
AB  - PURPOSE: To describe the current educational technology infrastructure and
      services provided by North American allopathic medical schools that are members
      of the Association of American Medical Colleges (AAMC), to present information
      needed for institutional benchmarking. METHOD: A Web-based survey instrument was
      developed and administered in the fall of 2004 by the authors, sent to
      representatives of 137 medical schools and completed by representatives of 88, a
      response rate of 64%. Schools were given scores for infrastructure and services
      provided. Data were analyzed with one-way analyses of variance, chi-square, and
      correlation coefficients. RESULTS: There was no difference in the number of
      infrastructure features or services offered based on region of the country,
      public versus private schools, or size of graduating class. Schools implemented
      3.0 (SD = 1.5) of 6 infrastructure items and offered 11.6 (SD = 4.1) of 22
      services. Over 90% of schools had wireless access (97%), used online course
      materials for undergraduate medical education (97%), course management system for
      graduate medical education (95%) and online teaching evaluations (90%). Use of
      services differed across the undergraduate, graduate, and continuing medical
      education continuum. Outside of e-portfolios for undergraduates, the least
      offered services were for services to graduate and continuing medical education.
      CONCLUSIONS: The results of this survey provide a benchmark for the level of
      services and infrastructure currently supporting educational technology by AAMC
      member allopathic medical schools.

PMID- 16799286
TI  - Reflective teaching practices: an approach to teaching communication skills in a
      small-group setting.
AB  - Small-group teaching is particularly suited for complex skills such as
      communication. Existing work has identified the basic elements of small-group
      teaching, but few descriptions of higher-order teaching practices exist in the
      medical literature. Thus the authors developed an empirically driven and
      theoretically grounded model for small-group communication-skills teaching.
      Between 2002 and 2005, teaching observations were collected over 100 hours of
      direct contact time between four expert facilitators and 120 medical oncology
      fellows participating in Oncotalk, a semiannual, four-day retreat focused on end
      of-life communication skills. The authors conducted small-group teaching
      observations, semistructured interviews with faculty participants, video or audio
      recording with transcript review, and evaluation of results by faculty
      participants. Teaching skills observed during the retreats included a linked set
      of reflective, process-oriented teaching practices: identifying a learning edge,
      proposing and testing hypotheses, and calibrating learner self-assessments. Based
      on observations and debriefings with facilitators, the authors developed a
      conceptual model of teaching that illustrates an iterative loop of teaching
      practices aimed at enhancing learners' engagement and self-efficacy. Through
      longitudinal, empirical observations, this project identified a set of specific
      teaching skills for small-group settings with applicability to other clinical
      teaching settings. This study extends current theory and teaching practice
      prescriptions by describing specific teaching practices required for effective
      teaching. These reflective teaching practices, while developed for communication
      skills training, may be useful for teaching other challenging topics such as
      ethics and professionalism.

PMID- 16799287
TI  - The red hat.

PMID- 16799291
TI  - Stories from the field: students' descriptions of gender discrimination and
      sexual harassment during medical school.
AB  - PURPOSE: Previous studies have documented the prevalence of gender discrimination
      and sexual harassment during medical training, but very few have examined the
      behaviors that students perceive as discriminatory or harassing. The authors
      addressed this lack of information by examining graduating medical students'
      written descriptions of personal experiences with such behaviors during medical
      school. METHOD: The authors reviewed the responses of graduating seniors at 12
      U.S. medical schools to a questionnaire, administered in 2001-02, that asked them
      to provide written descriptions of their personal experiences with gender
      discrimination and sexual harassment. Seven response categories were created on
      the basis of recurring themes: educational inequalities; stereotypical comments;
      sexual overtures; offensive, embarrassing, or sexually explicit comments;
      inappropriate touching; sexist remarks; and not classifiable. The three authors
      examined the students' written accounts and placed each into one or more of the
      categories. RESULTS: Of the students' responses, 290 (36.6%) contained 313
      written descriptions of personal experiences that the students perceived as
      either discriminatory or harassing. The most frequently reported experiences
      involved educational inequalities; experiences in this category were reported
      more frequently by men than by women. All other categories of experiences were
      reported more frequently by women. CONCLUSIONS: The results support earlier
      findings of the prevalence of gender discrimination and sexual harassment during
      undergraduate medical education. Perhaps formal antiharassment policies should
      provide examples of unacceptable behavior that are based on categories such as
      those revealed by this analysis. Perhaps, too, medical students' comments could
      be used to develop educational interventions for physicians in supervisory
      positions.

PMID- 16799293
TI  - Learning in practice: experiences and perceptions of high-scoring physicians.
AB  - PURPOSE: To increase understanding of informal learning in practice (e.g.,
      consulting with colleagues, reading journals) through exploring the experiences
      and perceptions of physicians perceived to be performing well. Objectives were to
      find out how physicians learned in practice and maintained their competence, and
      how they learned about the communication skills domain specifically. METHOD: Of
      142 family physicians participating in a formal multisource feedback (360-degree)
      formative assessment, 25 receiving high scores were invited to participate in
      interviews conducted in 2003 at Dalhousie University Faculty of Medicine. Twelve
      responded. Interviews were 1.5 hours each, recorded, transcribed, and analyzed by
      the research team using accepted qualitative procedures. RESULTS: While formal
      learning appeared important to most, informal learning, especially through
      patients and colleagues, appeared to be fundamental. The physicians appeared to
      learn intentionally from practice and work experiences, and reflection appeared
      integral to learning and monitoring the impact of learning. Two findings were
      surprising: participants' conceptions of competence and perceptions that
      communication skills were innate rather than learned. CONCLUSIONS: These
      physicians' ways of intentional learning from practice concur with current models
      of informal learning. However, informal learning is largely unrecognized by
      formal institutions. Additionally, the physicians did not in general share
      notions of professional competence held by educators and others in authority.
      These findings suggest the need to make implicit content and learning processes
      more explicit. Additional research areas include exploring whether physicians
      across the range of performance levels demonstrate similar processes of
      reflective learning.

PMID- 16799294
TI  - Role modeling humanistic behavior: learning bedside manner from the experts.
AB  - PURPOSE: Humanistic care is regarded as important by patients and professional
      accrediting agencies, but little is known about how attitudes and behaviors in
      this domain are taught in clinical settings. To answer this question, the authors
      studied how excellent clinical teachers impart the behaviors and attitudes
      consistent with humanistic care to their learners. METHOD: Using an
      observational, qualitative methodology, the authors studied 12 clinical faculty
      identified by the medical residents enrolled from 2003 to 2004 as excellent
      teachers of humanistic care on the inpatient medical services at four medical
      universities in the United States (University of Minnesota Medical School, Emory
      University, University of Rochester School of Medicine, and Baylor College of
      Medicine). Observations were conducted by the authors using standardized field
      notes. After each encounter, the authors debriefed patients, learners (residents
      and medical students), and the teaching physicians in semistructured interviews.
      RESULTS: Clinical teachers taught primarily by role modeling. Although they were
      highly aware of their significance as role models, they did not typically address
      the human dimensions of care overtly. Despite the common themes of role modeling
      identified, each clinical teacher exhibited unique teaching strategies. These
      clinical teachers identified self-reflection as the primary method by which they
      developed and refined their teaching strategies. CONCLUSIONS: Role modeling is
      the primary method by which excellent clinical teachers try to teach medical
      residents humanistic aspects of medical care. Although clinical teachers develop
      unique teaching styles and strategies, common themes are shared and could be used
      for the future development of clinical faculty.

PMID- 16799296
TI  - Empowering junior faculty: Penn State's faculty development and mentoring
      program.
AB  - Empowerment of faculty is essential for academic success. The Junior Faculty
      Development Program (JFDP), sponsored by the Office of Professional Development
      of the Penn State College of Medicine, was established in 2003 with the goal of
      promoting the development and advancement of junior faculty so they can achieve
      success in their academic careers. The program consists of two components: a
      curriculum in research, education, clinical practice, and career development, and
      an individual project completed under the guidance of a senior faculty mentor.
      The curriculum provides faculty with knowledge, skills, and resources. Mentoring
      provides relationships and support. Together, these elements combine to empower
      junior faculty to better manage their careers. The effectiveness of the program
      has been demonstrated by several measures: participants evaluated the program
      highly, demonstrated increases in their perceptions of their own abilities, and
      completed tasks important to the advancement of their careers. Participants
      stated they were better prepared to advance their academic careers and that the
      individual projects would contribute to their career advancement. On the basis of
      this experience, the authors suggest that faculty development programs should
      empower faculty so that they can more effectively chart a successful career in
      academic medicine. This report describes an empowerment model, and the design,
      implementation, and evaluation of the Junior Faculty Development Program in 2003
      04 and 2004-05. The authors offer this program as a model for the benefit of
      other institutions and for one of their most valuable assets: junior faculty.

PMID- 16799297
TI  - Repaving the road to academic success: the IMeRGE approach to peer mentoring.
AB  - In recent years, academic health centers have made a considerable effort to
      encourage medical students and physicians-in-training to consider academic
      medicine as a career choice. For physicians, selecting a career in academic
      medicine may be the first hurdle, but the challenge of successfully maintaining
      an academic career is perhaps a more formidable task. Mentoring is a much-needed
      response to this challenge. But the success of traditional mentoring programs at
      academic institutions is often limited by, among other things, the availability
      of senior faculty who can serve as mentors. The authors describe the formation
      and organization of the Internal Medicine Research Group at Emory (IMeRGE), an
      innovative peer mentoring group within the Division of General Medicine at Emory
      University. This group, born partially out of the mentoring needs of our women
      and minority faculty, shared the primary goal of fostering a collaborative
      atmosphere among junior faculty, while simultaneously acquiring experience
      through advanced faculty development. The authors present our methods of
      garnering division support for designated time and financial resources, defining
      member responsibilities, developing a curriculum, providing peer support, and
      seeking advisors with expertise in the areas on which we wished to focus. In
      addition to the development of IMeRGE, the authors provide an overview of the
      pros and cons of traditional mentoring versus peer mentoring; discuss the
      challenges faced by IMeRGE and strategies for addressing these issues; and
      present the paradigm of IMeRGE as a template for alternative forms of academic
      mentorship.

PMID- 16799299
TI  - Nonexpansive immediate breast reconstruction using human acellular tissue matrix
      graft (AlloDerm).
AB  - Immediate breast reconstruction has become a standard of care following
      mastectomy for cancer, largely due to improved esthetic and psychologic outcomes
      achieved with this technique. However, the current historical standards-
      transverse rectus abdominis myocutaneous flap reconstruction and expander-
      implant surgery-still have limitations as regards patient morbidity, short-term
      body-image improvements, and even cost. To address these shortcomings, we employ
      a novel concept of human tissue replacement to enhance breast shape and provide
      total coverage, enabling immediate mound reconstruction without the need for
      breast expansion prior to permanent implant placement. AlloDerm (human acellular
      tissue matrix) is a human-derived graft tissue with extensive experience in
      various settings of skin and soft tissue replacement surgery. This report
      describes the success using acellular tissue matrix to provide total coverage
      over the prosthesis in immediate reconstruction, with limited muscle dissection.
      In this population, 49 patients (76 breasts) successfully underwent the acellular
      tissue matrix-based immediate reconstruction, resulting in durable breast
      reconstruction with good symmetry. These findings may predict that acellular
      tissue matrix-supplemented immediate breast reconstruction will become a new
      technique for the immediate reconstruction of the postmastectomy breast.

PMID- 16799300
TI  - Clinical imaging diagnosis of implant materials for breast augmentation.
AB  - BACKGROUND: The ingredients of substances implanted for breast augmentation
      sometimes remain unknown due to lack of information from patients. Significant
      clinical problems sometimes necessitate removal and reconstruction. Thus,
      preoperative diagnostic imaging to identify the ingredients of implants may
      improve the treatment decision-making process. In this report, we created a
      clinical imaging index. PURPOSE: Here, we summarize computed tomography (CT) and
      magnetic resonance imaging (MRI) imaging of implant materials to predict the
      ingredients of implant substances preoperatively. METHODS: A total of 104
      patients with late complications after receiving breast augmentations between
      1971 and 2002 were examined using CT and MRI. In addition, further examinations
      were conducted, including postoperative chemical analysis using Nuclear magnetic
      resonance (NMR) spectroscopy and MRI imaging of various implanted substances
      using an experimental magnetic resonance system. RESULTS: We identified the
      ingredients of implant materials used for breast augmentation by imaging
      diagnostics as follows: silicone: radiopaque-low/high (CT-MRI T1/T2); hydrogel:
      radiolucent-low approximately iso/high; hydrocarbon: radiolucent-high
      approximately iso/low approximately iso; saline: radiolucent-low/high.
      CONCLUSION: We have identified by imaging diagnosis the ingredients of implant
      materials.

PMID- 16799301
TI  - Results of partial fasciectomy for Dupuytren disease in 261 consecutive patients.
AB  - Many different surgical techniques are still being used for Dupuytren disease.
      The outcome of 558 consecutive operations with 1 technique was reviewed. Distinct
      subgroups were made to detect risk factors for a poor outcome and complications.
      The mean follow-up time was 7.3 years. Younger patients (first surgery before 45
      years) were operated significantly more than older patients (after 45 years).
      Results of contracted proximal interphalangeal (PIP) joints were significantly
      worse than other joints. The overall complication rate was 26%. Nerve lesions
      occurred in 7.7%. Young age proved to be a prognostic factor for the total number
      of operations. The contracted PIP joints will lead to more complications and
      poorer result. The risk at nerve lesion, necrosis, and infection are higher for
      recurrent surgery. These findings can be used in advising patients.

PMID- 16799302
TI  - Frozen-food-related hand injuries.
AB  - Attempting to separate frozen food with a knife can result in serious injury to
      the hand. This injury is prevalent and is a common reason for referral to hand
      surgeons. Ten cases were reviewed over a 3-month period; the causative frozen
      food varied widely. Seven of the 10 patients required surgical exploration, and
      of these 7 patients, 3 were found to have significant injury. The injuries varied
      from digital nerve injuries to damaged flexor tendons. The other 4 patients were
      all found to have only soft tissue damage.

PMID- 16799303
TI  - Laser treatment of venous malformations.
AB  - Venous malformations (VM) are developmental errors comprised of enlarged
      dysplastic blood vessels. Clinically they manifest as either a faint blue patch
      or a soft blue vascular mass. Treatment options include a sclerosing agent (such
      as alcohol or ethiblock), surgery or laser therapy. A review of the literature
      concerning VM and laser treatment yielded a few sporadic reports describing
      series of 3 to 46 cases. In this retrospective study we reviewed the files of the
      relevant cases. The data included the extent of the lesion, the different
      anatomical sites, age of patient and the extent of clearance of the lesion as the
      treatment's end point. This study includes 56 cases which makes it the largest
      series presented. The success rate of laser treatment was 92.8%. The immediate
      complication rate was very low (approximately 3.57%) including minimal scarring
      and deformity. No long term complications were noted. Our study concludes that
      treatment of VM is a difficult task due to the nature of the lesions. Laser
      treatment of these lesions enables one to obtain good results with a very low
      incidence of complications. Surgery and other treatment modalities are not always
      satisfactory, yield similar or less efficient results and have a higher
      complication rate. Laser treatment can play an important role in the treatment of
      VM and in fact may be the treatment of choice in some settings.

PMID- 16799304
TI  - The effect of varying pulse duration, wavelength, spot size, and fluence on the
      response of previously treated capillary vascular malformations to pulsed-dye
      laser treatment.
AB  - Modern lasers allow different parameters to be altered in an effort to gain
      further improvement in otherwise resistant capillary vascular malformations
      (CMs). The aim of this study was to examine the effect of changing the pulse
      duration, wavelength, spot size, and fluence on the color and capillary
      architecture of 585-nm pulsed-dye, laser-resistant CMs. Eighteen patients were
      assessed with a depth measurement videomicroscope (DMV) before and after 12 test
      patches with ScleroPlus and V-Beam lasers at specified parameters. In the
      majority of the test patch areas, there was little improvement after treatment.
      However, 44% of patients had greater than 75% clearance in at least 1 test patch
      site. This study demonstrates that both lasers can achieve further lightening in
      585 nm 0.45 msec pulsed-dye laser-resistant CMs. However, in CMs consisting of
      small-diameter deep vessels, further improvement is unlikely.

PMID- 16799305
TI  - Electrosurgery in patients with pacemakers/implanted cardioverter defibrillators.
AB  - Despite improved protective mechanisms, pacemakers and implanted cardioverter
      defibrillators are subject to interference from various sources. An effective
      means of hemostasis, electrocautery generates electromagnetic interference and
      may be problematic in this patient population. Reported complication rates are
      low, but the consequences can be serious. Recommendations regarding the
      management of patients with implanted cardiac devices become increasingly
      significant both as the number of patients with devices increases and the number
      of out-of-hospital/minor surgery procedures performed increases. This article
      provides surgeons and anesthetists with practical recommendations for use of
      electrocautery in patients with pacemakers or implantable cardiac defibrillators.

PMID- 16799306
TI  - Measures to prevent complications of distally based neurovascular sural flaps.
AB  - Several publications in recent years have proven unbroken popularity of
      superficial sural artery flaps for the coverage of defects of the lower leg and
      proximal foot. However, complications are being discussed rarely. The realistic
      complication rate is up to 59%, given corresponding comorbidities, risk factors,
      or performance errors. Twelve distally based neurovascular sural flaps were used
      for reconstruction of heel, ankle, and lower-leg defects between 2003 and 2005.
      The following pre- and postoperative procedures were performed as a routine: An
      additional arteriography was done preoperatively to prove the patency of the
      peroneal artery. Acoustic Doppler ultrasound was used to identify the lesser
      saphenous vein and the concomitant vessels (perforators of the peroneal artery)
      of the sural nerve. An enlarged skin paddle with a tail of skin over the pedicle
      at the point of rotation was harvested intraoperatively to take pressure off the
      vessels and facilitate primary closure. Postoperatively, external fixation
      provides strict immobilization of the affected leg. Following these measures, no
      flap loss was observed in the presented series, and only few minor complications
      occurred.

PMID- 16799307
TI  - Comparison of clinical evaluation and neurosensory testing in the early diagnosis
      of superimposed entrapment neuropathy in diabetic patients.
AB  - Diabetic patients are more susceptible to the development of entrapment
      neuropathy than nondiabetics. Since these patients suffer from a slowly
      progressing diabetic polyneuropathy, standard neurosensory and motor tests of
      nerve function are not sufficient in the diagnosis of superimposed nerve
      compression. This is most evident in the early stages of compression when
      quantitative diagnosis is important for making decisions on surgical
      decompression. We evaluated the validity of computer-assisted pressure-specified
      sensory device (PSSD) testing in the early detection of superimposed entrapment
      in diabetic neuropathy in comparison with standard clinical tests. Twenty-five
      diabetic patients with complaints of peripheral nerve dysfunction were evaluated
      by clinical tests and PSSD. Out of those, nerve entrapment was detected in 15
      patients (60%) (9 in late and 6 in early stage) by neurosensory PSSD testing.
      Standard clinical tests were confirmative in 33.3% of these cases (44% of late
      and 16.7% of early stage). Out of 144 evaluated nerves, 50 were diagnosed with
      entrapment (24 in late and 26 in early stage) using PSSD. Clinically, diagnosis
      was confirmed in 16% of entrapped nerves (20.8% of late and 11.5% of early
      stage). Average diabetes duration in patients with entrapment diagnosed using
      PSSD was significantly shorter than for those diagnosed clinically (4.14 +/- 2.04
      vs. 7.2 +/- 1.3, respectively; P = 0.005). Among evaluated factors, mean age and
      diabetes duration were found to be significantly shorter in patients with
      entrapment than in those with advanced diffused changes (54.47 +/- 13.07 vs.
      67.10 +/- 14.2; P = 0.019 and 5.33 +/- 3.74 vs.14.22 +/- 8.17; P = 0.006;
      respectively). Our results revealed higher sensitivity of PSSD in comparison with
      standard clinical tests in the detection of early-stage entrapment in patients
      with diabetes. To assess accuracy of PSSD in the proper patients' qualification
      for surgery, further prospective, postoperative studies are needed.

PMID- 16799308
TI  - Analysis of velopharyngeal morphology in adults with velopharyngeal incompetence
      after surgery of a cleft palate.
AB  - This study analyzed the relationship of velopharyngeal morphology and
      velopharyngeal function among 13 adults with velopharyngeal incompetence (VPI),
      14 adults with velopharyngeal competence (VPC) after primary surgical treatment
      of cleft palate, and 20 noncleft adults. The measurements included velar length,
      pharyngeal depth, pharyngeal height, and the need ratio of pharyngeal depth to
      velar length. In addition, the cranial base, cervical vertebrae, posterior nasal
      spine, and also the position of the posterior pharyngeal wall (PPW) in the
      pharyngeal triangle were analyzed. All data were subjected to the Student t test
      of statistical significance. The results showed that the VPI group had normal
      pharyngeal depth and a significantly shorter velar length, resulting in a greater
      depth/length ratio than those of the VPC group and normal control subjects. The
      position of PPW in the pharyngeal triangle was located significantly more
      superior in the VPI group compared with the VPC group and normal control
      subjects. Measurements of the anteroposterior and the vertical dimensions in the
      regions of the cranial base and cervical vertebrae revealed no significant
      difference among the 3 groups. According to this study, the velopharyngeal
      morphology of adults with VPI is characterized by a shorter palate, greater need
      ratio, slightly counterclockwise-rotated pharyngeal triangle, and superiorly
      positioned PPW.

PMID- 16799309
TI  - Incidence and cluster occurrence of palatal fistula after furlow palatoplasty by
      a single surgeon.
AB  - Fifty-seven cleft palate patients underwent primary repair with Furlow
      palatoplasty by the same surgeon from January 2001 to January 2005. There were 8
      fistulae, 7 of which occurred out of 9 patients treated between July 2003 and
      January 2004 when operations were resumed after the outbreak of severe acute
      respiratory syndrome in Hong Kong; 1 minute fistula occurred after this period
      and closed spontaneously. Longer operation time and higher proportion of Veau
      classes III and IV clefts were noted in the fistula group. The high incidence and
      cluster occurrence immediately after SARS could be related to changes in the
      provision of nursing care and the level of parental supervision, in addition to
      more difficult operations encountered as reflected by more extensive clefts and
      longer operation time. We would like to emphasize that expert nursing care and
      close supervision with the help of parents play a very important role in
      achieving the best possible clinical outcome from cleft palate surgery in
      pediatric patients.

PMID- 16799310
TI  - An alternative dressing material for the split-thickness skin graft donor site:
      oxidized regenerated cellulose.
AB  - The split-thickness skin graft (STSG) donor sites have been treated with various
      and plenty of dressing techniques and materials. An ideal STSG donor site
      dressing should have antibacterial, hemostatic, and promoting epidermal healing
      properties. We have performed a prospective study to evaluate the effect of the
      oxidized regenerated cellulose on STSG donor site healing. Between January 2002
      and January 2005, 40 patients who were operated in any kind of reconstructive
      operations with STSG donor sites were included in the study. One half of the
      wound was covered with oxidized regenerated cellulose and the other half of the
      same wound of the same patient was covered with fine mesh gauze treated with
      Furacin (nitrofurazone). The patients were grouped into 2 depending on the
      dressing technique: group I, semiclosed and group II, closed. The wounds were
      evaluated for healing time, infection, pain perception of the patient, and final
      esthetic results. The oxidized regenerated cellulose side of the group I was
      healed in a mean of 6.5 +/- 0.51 days; in group II, 5.4 +/- 0.50 days (range, 5-6
      days). The fine mesh gauze treated with Furacin in group I was healed in a mean
      of 9.9 +/- 0.97 days (range, 8-11 days); in group II, 8.4 +/- 0.99 days (range, 7
      10 days). There was a statistical significance between the oxidized regenerated
      cellulose side and the fine mesh gauze side (P < 0.001) in group I and group II
      separately. The difference between group I and group II was statistically
      significant in the oxidized regenerated cellulose side (P < 0.001), and the
      difference between group I and group II was statistically significant in the fine
      mesh gauze side (P < 0.005). The antibacterial, hemostatic, and absorbable
      property of the oxidized regenerated cellulose could ensure the utilization as an
      alternative STSG donor site dressing, especially because the positive influence
      over the wound healing was proven.

PMID- 16799312
TI  - Melanoma of the ear: treatment and survival probabilities based on 199 patients.
AB  - BACKGROUND: In 2005, it is now estimated that one in 62 Americans have a lifetime
      risk of developing invasive melanoma. Melanoma of the ear accounts for 1% of all
      cases of melanoma and 14.5% of all head and neck melanomas. With this increase in
      incidence, plastic surgeons will likely have to treat and manage more of these
      patients in the future. METHODS: A retrospective chart review was performed on
      199 patients diagnosed with primary melanoma of the ear. Specimens were reviewed
      by same center dermatopathologists (Duke University Medical Center, Durham, NC)
      for standardization of histologic criteria in all but 10 patients. Surgical
      treatment and outcomes were reviewed and survival rates based on thickness and
      stage were calculated. Metastases information, anatomic location on the ear, and
      histologic subtype were recorded and analyzed. RESULTS: The median length of
      follow up was 3.3 years with a range of 0.4 to 24.9 years. Eighty-six patients
      were known to be dead at the last known follow-up date. The median survival time
      among these patients was 7.9 years. The most common histologic classification of
      the lesions were superficial spreading type (45.2%) and were most likely to be
      localized to the anterior helix (49.3%). One hundred sixty-one of 199 (80.9%)
      patients underwent wide local excision with local recurrence rate of 10.6%.
      Overall, 43.2% of patients developed a local recurrence or metastatic spread.
      Ulceration, thickness, and stage all negatively affected survival. CONCLUSIONS:
      This is the largest review of primary ear melanoma cases reported to date.
      Survival probabilities at 2, 5, and 10 years for melanoma of the ear based on
      thickness and stage are presented. Ulceration adversely affected survival
      probability (P < 0.003). Lesion excision with confirmed negative margins on
      permanent section pathology should be the goal of initial surgical therapy, and
      there is no apparent role for elective lymph node dissection in treatment of
      melanoma of the ear.

PMID- 16799311
TI  - Mycobacterium ulcerans ulcers: a proposed surgical management algorithm.
AB  - Mycobacterium ulcerans (MU) is the third common mycobacterial infection after
      tuberculosis and leprosy. In endemic areas, MU ulcers should be considered in the
      differential diagnosis of any unusual or nonhealing lesion or ulcer. Diagnosis
      and treatment should be instigated promptly. Delay may lead to disfiguring or
      disabling scars. Surgical management, therefore, should aim towards early
      excision, with clear margins of the ulcer. We present 4 consecutive patients
      treated by our department within a 6-month period for MU ulcers. The
      presentation, diagnosis and surgical management are described. Based on our
      experience and after reviewing the literature, we have developed a surgical
      algorithm for the management of MU ulcers.

PMID- 16799313
TI  - Hand knife versus powered dermatome: current opinions, practices, and evidence.
AB  - Some surgeons prefer to use powered dermatomes when harvesting split-thickness
      skin grafts, while others prefer the hand knife. We conducted a postal survey of
      British plastic surgery units, contacted medicolegal departments, and
      investigated the literature to explore the reasoning for any preferences and the
      existing evidence to support such practices. Two hundred thirty-eight surgeons
      from 30 units replied, 145 (61%) preferring to use the powered dermatome,
      primarily as they believed it provided for better-quality graft and donor sites.
      Ninety-five (40%) respondents felt they were potentially open to successful
      litigation by using a hand knife when a powered dermatome was available. We found
      no evidence to support such clinical or medicolegal views and conclude that
      numerous misconceptions exist about skin-graft harvesting instruments. We suggest
      that surgeons should use whichever instrument they feel will, in their hands,
      provide the optimum result and not be directed by unfounded opinions.

PMID- 16799314
TI  - A new technique for microvascular anastomosis: eversion with 3 horizontal
      mattress sutures.
AB  - In our experimental study of a new microvascular anastomosis technique, we
      divided 30 Wistar albino rats into 2 groups. We performed the classic interrupted
      suture anastomosis technique in group 1 (n = 15) and our new technique, using 3
      horizontal mattress sutures, in group 2 (n = 15). We checked patency immediately
      following anastomosis, at the end of the first hour, and at the end of the third
      week postanastomosis. While the patency rates for both techniques were 100% at
      the end of the first hour, the respective values were 100% and 93.4% by the end
      of the third week. Using light microscopy, lumen patency, intimal and medial
      damage, inflammation, and granulation were evaluated histopathologically. The
      mean anastomosis time for the experimental group (15 minutes) was shorter than
      that for the classic group (mean 21 minutes), and the difference was
      statistically significant (P < 0.01), while the difference between the patency
      rates was not significant (P = 0.05). Therefore, provided that the incisions are
      made correctly, our microvascular anastomosis technique using 3 horizontal
      mattress sutures can be used in experimental and clinical studies.

PMID- 16799315
TI  - A hemodynamic study of the effects of arterial anastomoses with interrupted
      simple versus horizontal mattress sutures on rat epigastric flap perfusion.
AB  - The effects of interrupted simple versus horizontal mattress sutures and of the
      internal diameter of the arterial pedicle at the level of the anastomosis on rat
      epigastric flap perfusion were investigated. In the first group, a microclip was
      applied to the femoral artery for 30 minutes. In the second group, the artery was
      cut, and a classic 7- to 8-suture microarterial end-to-end anastomosis was
      performed. In the third group, the artery was cut, and a microarterial end-to-end
      anastomosis with 3 horizontal mattress sutures at 120-degree intervals was
      performed. Perfusion was measured using a laser Doppler flowmeter (Periflux 2B,
      Perimed, Sweden) at 3 zones of the flap at 30 and 60 minutes and at 21 days after
      the procedure. Internal vascular diameters were measured histopathologically.
      Perfusion was better in the control group than in the experimental groups.
      However, the internal vascular diameters were greater with the classic method
      than with the new method, and the perfusion did not differ statistically in the
      anastomosis groups. In conclusion, even when significant narrowing develops at
      the anastomosis, flap viability is not affected.

PMID- 16799316
TI  - Osteogenic potentiation of human adipose-derived stem cells in a 3-dimensional
      matrix.
AB  - Adipose-derived stem cells (ADSCs) hold promise for use in tissue engineering.
      Despite growing enthusiasm for use of ADSCs, there is limited research that has
      examined their behavior in different in vitro and in vivo systems. The purpose of
      our study was to evaluate the effect of the extracellular matrix structure and
      composition on osteogenic differentiation by comparing the osteogenic marker
      expression of ADSCs grown under 2-dimensional or 3-dimensional cell culture
      conditions. Group 1 (2-D) included ADSCs raised under conventional cell culture
      conditions (cells in a 2-D monolayer configuration) (n = 24), and group 2 (3
      dimensional) included ADSCs seeded in a collagen gel (cells within a 3
      dimensional, biologically active environment) (n = 24). Comparison of ADSC
      behavior between the 2 groups was analyzed during a 14-day time frame. Osteogenic
      marker expression (CBFA-1, alkaline phosphatase, osteonectin, osteopontin,
      Collagen I, and JNK2) was quantified by real-time PCR, and histologic analysis
      was performed. Histologically, group 1 (2-D) showed cell spreading and deposition
      of a calcified extracellular matrix. Group 2 (3-dimensional) assumed a
      disorganized state in the collagen gel, with extension of pseudopodia throughout
      the matrix. Expression of CBFA-1 was up-regulated immediately in both groups.
      However, cells in group 2 (3-dimensional) had a more rapid and greater overall
      expression compared with cells in group 1 (2-D) (250-fold greater at 4 days). At
      day 14, cells in group 2 (3-dimensional) showed greater expression of all other
      osteogenic markers than cells in group 1 (2-D) (2.3-fold greater expression of
      alkaline phosphatase [P < 0.05], 8.4-fold greater expression of osteonectin [P <
      0.05], 6.4-fold greater expression of osteopontin [P < 0.05], 2.9-fold greater
      expression of collagen I [P < 0.05], and 2.5-fold greater expression of JNK2 [P <
      0.05]). Our data showed there was a progressive stimulatory effect on ADSCs with
      regard to osteogenesis when cultured in a 3-dimensional gel compared with a 2-D
      monolayer.

PMID- 16799317
TI  - ATP-sensitive potassium channels mediate the anti-ischemic properties of ischemic
      and pharmacologic preconditioning in rat random-pattern skin flap.
AB  - Ischemic preconditioning (IPC) and pharmacologic preconditioning by morphine and
      adenosine may significantly decrease the amount of necrosis in rat random pattern
      skin flaps. We examined the role of ATP-sensitive potassium channels (K(ATP)
      channels) in mediating these protective phenomenon by using glibenclamide a
      nonspecific blocker of these channels. We also investigated whether
      administration of diazoxide an opener of the K(ATP) channels could mimic the same
      protective effect. Ninety male Sprague-Dawley rats were randomly divided into
      either control or treatment groups (n = 6 each). Bipedicled dorsal skin flaps (2
      x 8 cm) were elevated at the midline. In pharmacologic preconditioning groups, 1
      mL of morphine (5 mg/flap), adenosine (0.5 mg/flap), or different doses of
      diazoxide (0.5, 1, 5, and 15 mg/flap) were administered locally in the cranial
      half of the flap, respectively. One milliliter of saline was locally injected in
      the control group. In the IPC group, 1 hour after local saline injection the
      cranial pedicle was clamped for 20 minutes, and then 40 minutes' reperfusion was
      performed. In another experiment, 0.3 mg/kg of glibenclamide was injected
      intraperitoneally 30 minutes before local administration of saline or drug in
      ischemic or pharmacologic preconditioning groups. Regardless of the group, all
      flaps were cut at the cranial side 2 hours after elevation and were sutured back.
      Flap survival area was evaluated on the seventh postoperative day. IPC and
      pharmacologic preconditioning with morphine, adenosine, and diazoxide (in higher
      doses; 1, 5, and 15 mg/flap) improved survival area compared with the control
      group. Glibenclamide abolished their protective effect. K(ATP) channels may have
      a key role in anti-ischemic properties of IPC and pharmacologic preconditioning.

PMID- 16799318
TI  - A true one-stage nonmicrosurgical technique for total phallic reconstruction.
AB  - A new nonmicrosurgical technique for one-stage total phallic reconstruction is
      presented. In this procedure, an innervated anterolateral thigh (ALT) flap
      including the medial half of the fascia latae is combined with a sartorius
      perforator flap. Both flaps are elevated together as an island chimeric flap
      based on the lateral circumflex femoral vessels and tunneled to the recipient
      area. The neourethra is created with thin and hairless skin of the sartorius
      perforator flap, while the ALT flap is used to construct the shaft and glans of
      the neophallus. The rigidity was provided with a penile prosthesis covered with a
      neotunica albuginea created with vascularized fascia latae for the first time in
      the literature. The lateral femoral cutaneous nerve of the ALT flap is coapted to
      the pudendal nerve to provide erogenous sensibility. Here, a 15-year-old male in
      whom this new procedure was used for one-stage total phallic reconstruction is
      presented. Two years of follow-up revealed that an esthetically acceptable and
      functional neopenis with a nonhairy competent urethra, erogenous sensitivity, and
      a proper rigidity was achieved with no complication. This new technique, namely,
      the "Istanbul on the thigh" flap, is a one-stage, safe, and timesaving technique
      which fulfills all essential goals of phallic reconstruction but does not require
      microsurgical equipment and expertise. Moreover, the donor scar is located at an
      unexposed area, easy to conceal. Although more clinical experience is needed,
      this new procedure seems to be a useful alternative in phallic reconstruction.

PMID- 16799319
TI  - An unusual congenital facial anomaly: erectile proboscis-like structure.
AB  - We report a 3-week-old male infant with an unusual congenital facial anomaly,
      which is characterized by a proboscis-like erectile structure arising from the
      right malar region. Although it is a tubular structure resembling the proboscis
      lateralis, this case was more likely to be a new congenital anomaly because of
      the following reasons: (1) in contrast with the proboscis lateralis, which
      originates from the medial portion of the orbital roof, the structure was located
      at the right malar region in our case; (2) although it was soft and freely
      dangling on the face, this proboscis-like structure was strongly erectile, with
      contraction of the orbicularis oculi muscle when the infant cried; (3)
      histopathological examination revealed that the structure was composed by normal
      fibroadipose tissue and striated muscle covered with a healthy skin and
      subcutaneous tissue. In contrast with histopathological characteristics of a
      proboscis lateralis, there was neither osteocartilaginous tissue nor mucosa in
      the structure. Although it is a typical finding for a proboscis lateralis, no
      lumen was found in the presented anomaly. Because of these unique
      characteristics, which remarkably differ from previously reported facial
      anomalies, we thought this case worth reporting. A literature review revealed
      that no similar case has been reported in the literature.

PMID- 16799320
TI  - Flexor pollicis brevis adductorplasty: an alternative method in ulnar nerve
      paralysis.
AB  - Loss of pinch power associated with loss of coordinated movement of thumb and
      index fingers is the major disability in patients with ulnar nerve paralysis.
      Several tendon transfer methods utilizing different donor muscles have been used
      to restore adductor pollicis muscle function in ulnar nerve paralysis. In this
      paper, we discuss the transfer of flexor digitorum brevis muscle to the tendon of
      adductor pollicis muscle as an alternative method to restore key pinch in ulnar
      nerve paralysis. The technique was applied to 4 patients with ulnar nerve
      paralysis. Before clinical application, an anatomic study was carried out in 6
      cadaver hands. In cadavers, radial and ulnar arteries were injected with latex
      and arterial pedicles of flexor pollicis brevis muscle were dissected under 4x
      magnification. Also, motor branches from the median nerve were shown at the
      entrance point to the muscle. In surgical practice, the superficial head of the
      muscle is detached from its insertion and the minor pedicle of the muscle is cut.
      Muscle is dissected proximally up to two thirds of its length. The dominant
      pedicle of the muscle originating from superficial palmar arcus is preserved, and
      the muscle is sutured to the tendon of the adductor pollicis muscle close to its
      insertion. Patients were evaluated in terms of key pinch strength preoperatively
      and at the postoperative sixth month using a pinch meter (Chattanooga Group,
      Inc). Key pinch strengths were recorded and expressed as percentage of the
      strength of the contralateral uninvolved hand. Mean key pinch strength of our
      patients was 29.7%. In conclusion, we believe in that flexor pollicis brevis
      adductorplasty may be an alternative method for restoration of adductor pollicis
      muscle function in ulnar nerve paralysis.

PMID- 16799321
TI  - Scalpels and spark plugs.

PMID- 16799322
TI  - Use of wise pattern for achieving symmetry in one stage in immediate
      reconstructions with deep inferior epigastric artery perforator flap.

PMID- 16799323
TI  - Wow! It's a miracle inverted! (or is it?).

PMID- 16799324
TI  - For whom the bell tolls.

PMID- 16799325
TI  - Treatment of complex below-the-elbow gunshot wounds.

PMID- 16799326
TI  - Unexpected route of a bullet: from the frontal sinus to the gastrointestinal
      tract.

PMID- 16799327
TI  - Leech control: a cheap and simple method.

PMID- 16799328
TI  - A nasogastric catheter splint for a nailbed.

PMID- 16799329
TI  - Wise keyhole pattern rat vest.

PMID- 16799330
TI  - A review of antibody therapeutics and antibody-related technologies for oncology.

PMID- 16799331
TI  - Commentary on journal of immunotherapy paper by melenhorst et al.

PMID- 16799332
TI  - Efficacy of GM-CSF-producing tumor vaccine after docetaxel chemotherapy in mice
      bearing established Lewis lung carcinoma.
AB  - In this report, we evaluated the efficacy of a GM-CSF-producing tumor vaccine
      given before and after docetaxel in mice bearing established lung tumors. Mice
      bearing established 3LL tumors were treated with docetaxel and tumor vaccines
      transduced with either control or GM-CSF adenoviral vectors. Docetaxel (5-20
      mg/kg) treatment alone had only a minimal effect on growth of established 3LL
      tumors in vivo, although docetaxel was cytotoxic to 3LL cells in vitro. When mice
      bearing established 3LL tumors were pretreated with docetaxel followed by
      vaccination with irradiated GM-CSF- transduced 3LL tumor cells, significant tumor
      regression and prolonged survival were observed compared with chemotherapy alone.
      Delaying docetaxel treatment until after tumor vaccination abrogated the
      vaccine's anti-tumor effects. Mice that survived treatment were able to resist a
      lethal rechallenge of 3LL tumor cells. Memory CTL specific for an epitope (MUT-1)
      derived from 3LL were detected in surviving mice. Docetaxel induced a mild
      lymphodepletion in mice, both CD4 and CD8 subsets were reduced in LN and spleens.
      Interestingly, docetaxel also diminished the number of memory CD8+ T cells
      (CD122+) and possible CD4+ CD25+ Foxp3+ natural Treg cells. Docetaxel treatment
      did not affect antigen-driven proliferation of naive T cells but significantly
      promoted survival of activated T cells. Thus, augmentation of vaccine induced
      antitumor immunity in docetaxel-treated mice primarily due to the enhanced
      survival of antigen-experienced T cells.

PMID- 16799333
TI  - Immunostimulatory effects of CpG-ODN upon dendritic cell-based immunotherapy in a
      murine melanoma model.
AB  - In this study, we examined the protective and therapeutic efficacy of the
      immunoadjuvant CpG in combination with dendritic cell (DC) immunotherapy in a
      murine melanoma model. We found that murine bone-marrow derived DC stimulated in
      vitro with CpG displayed both enhanced expression of maturation markers and
      secretion of IL-12p70 and IL-10. In addition, these matured DC demonstrated
      enhanced ability to stimulate antigen specific CD4+ and CD8+ T cell responses in
      vitro. In a protection model, C57BL/6 mice vaccinated with either antigen-pulsed
      immature or CpG matured DC were unable to reject a lethal B16 melanoma challenge.
      In contrast, long-term protection was achieved in mice vaccinated with both CpG
      and antigen-pulsed DC, which correlated with an enhanced antigen specific T cell
      immune response. In a therapeutic model of established subcutaneous B16 melanoma,
      C57BL/6 mice treated intratumorally with CpG and B16 lysate-pulsed DC
      demonstrated a reduced tumor burden and prolonged survival. In a similar model of
      established subcutaneous tumor, mice treated with CpG-matured DC pulsed with a
      melanoma peptide, TRP-2, alone were unable to achieve tumor regression.
      Conversely, mice that received the combined vaccine of CpG and peptide-pulsed DC
      displayed a reduced tumor burden. These experiments provide evidence that
      combined immunization with both antigen-pulsed DC and the immunoadjuvant, CpG,
      can lead to tumor regression and long-term survival in a murine B16 melanoma
      model.

PMID- 16799334
TI  - Ex vivo-activated human macrophages kill chronic lymphocytic leukemia cells in
      the presence of rituximab: mechanism of antibody-dependent cellular cytotoxicity
      and impact of human serum.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is one of the mechanisms of tumor
      killing during antibody (Ab) immunotherapy, and a role for myeloid cells as
      effectors has been observed in several models. We are developing immunotherapy
      approaches based on administration of large numbers of ex vivo interferon-gamma
      activated macrophages to cancer patients. With a quantitative assay measuring
      killing of nonproliferating tumor cells, we evaluated whether, in physiologic
      conditions, these macrophages synergize with the anti-CD20 Ab rituximab for
      killing primary B-cell chronic lymphocytic leukemia (B-CLL) cells. ADCC reached
      levels of 70% to 80% at effector to target ratios as low as 1:1. Macrophage
      recruitment by Ab-opsonized tumor cells did not result in enhanced cytokine
      secretion, suggesting that the cytokine shower observed in rituximab-treated
      patients is not caused by macrophage activation, and that cytokines have no role
      in CLL killing. We observed that uptake of tumor material by macrophages was not
      directly correlated to tumor killing. Nonetheless, experiments in the presence of
      cytochalasin D showed that ADCC occurred mainly by phagocytosis. Tumor killing
      was largely mediated by Fc gammaRI and inhibited by increasing concentration of
      serum. Importantly, complement deposition on B-CLL cells did not seem to enhance
      macrophage ADCC in this model, as complement-depleted and complement-repleted
      human plasmas exerted comparable inhibition.

PMID- 16799335
TI  - Transduction of an HLA-DP4-restricted NY-ESO-1-specific TCR into primary human
      CD4+ lymphocytes.
AB  - cDNAs encoding functional T cell receptor (TCR) alpha and beta chains from a CD4+
      T cell line (SG6) generated by repeated stimulation of a melanoma patient's
      peripheral blood mononuclear cells with HLA-DP4-restricted, NY-ESO-1-specific
      peptide p161-180 were cloned using a 5'rapid amplification of cDNA end method.
      Three different TCR alpha chains and 7 TCR beta chains were found among the 84
      alpha and 162 beta cDNA clones tested. By screening different combination of the
      alpha/beta chains using RNA electroporation, TRAV9-1 (Valpha22.1) and TRBV20-1
      (Vbeta2) were found to be the functional pair in line SG6. Antibody blocking
      experiments confirmed that the specificity of TRAV9-1/TRBV20-1 mRNA-transfected T
      cells were CD4 dependent and HLA-DP4 restricted. A retroviral vector expressing
      both TRAV9-1 and TRBV20-1 was constructed and used for transduction of OKT3
      stimulated peripheral blood lymphocytes from melanoma patients. TCR-transduced
      CD4 T cells were capable of recognizing peptide-pulsed antigen-presenting cells
      (Epstein-Barr virus transformed B-cells, dendritic cells, and peripheral blood
      mononuclear cells), and protein-pulsed dendritic cells. Transduced cells were
      also capable of proliferation upon peptide stimulation and recognized peptide
      concentrations that were recognized by the parental line (0.2 microM). In
      contrast to SG6, which could not recognize human tumors, TCR-transduced CD4 T
      cells could specifically recognize NY-ESO-1/HLA-DP4-expressing melanoma cells.
      Major histocompatibility complex class II TCR-transduced CD4 T cells provides an
      alternative source of tumor antigen-specific T cells for adoptive immunotherapy
      of cancer patients.

PMID- 16799336
TI  - Dendritic cells matured with TNF can be further activated in vitro and after
      subcutaneous injection in vivo which converts their tolerogenicity into
      immunogenicity.
AB  - Dendritic cell (DC) maturation can occur by different types of stimuli.
      Previously, we described that murine DC matured with tumor necrosis factor (TNF)
      up-regulate surface MHC and costimulatory molecules but lack cytokine release,
      and therefore termed them semi-mature DC. These TNF/DC-induced tolerance after
      intravenous (i.v.) injection in a model of experimental autoimmune
      encephalomyelitis (EAE). Here, we show that TNF/DC are not terminally
      differentiated but can still respond to the microbial stimulus
      lipopolysaccharide. Subcutaneously injected TNF/DC induce an unpolarized
      T(H)1/T(H)2 response and are not protective in the experimental autoimmune
      encephalomyelitis model. Although TNF/DC home to the draining lymph node, they
      remain negative for intracellular cytokine stainings. However, the nonmigrating,
      endogenous DC started to produce interleukin (IL)-12p40, TNF and little IL-6, IL
      10, and MCP-1 in a bystander fashion. Together, DC matured with the inflammatory
      stimulus TNF remains responsive to further signals in vitro and in vivo. These
      signals can be provided by pathogens or the subcutaneous injection route, which
      can convert them from tolerogenic to immunogenic DC. These findings are important
      for selecting the appropriate injection route of human DC for tumor
      immunotherapy.

PMID- 16799337
TI  - Increased prevalence of regulatory T cells (Treg) is induced by pancreas
      adenocarcinoma.
AB  - We reported earlier that patients with breast or pancreas cancer have an
      increased prevalence of regulatory T cells (Treg) in the blood and tumor draining
      lymph nodes (TDLNs) compared with healthy individuals. In the current study, we
      tested the hypothesis that tumor cells promote the prevalence of Treg. The
      transforming growth factor-beta (TGF-beta) secreting murine pancreas
      adenocarcinoma, Pan02 cell line was injected into syngeneic C57BL/6 mice and the
      prevalence of Treg in the TDLNs and tumor spleen was measured weekly. Compared
      with control mice, the prevalence of CD25+ CD4+ cells in TDLNs and in tumor
      spleen increased with tumor growth. Analysis of these CD25+ CD4+ T cells in vitro
      confirmed expression of the Treg marker, Foxp3. In addition, their functional
      activity resembled that of Treg, as evidenced by a poor proliferative capacity;
      suppression of proliferation of CD25- CD4 or CD8T cells and inhibition of
      interferon-gamma release by CD25- CD4+ T cells. Reconstitution of Pan02-bearing
      Rag-/- mice with naive syngeneic CD25- CD4+ T cells induced CD25+ CD4+ Foxp3+ T
      cells in TDLNs, but not in the spleen. In contrast, Foxp3 was not detected in
      unreconstituted Pan02-bearing Rag-/- mice, or reconstituted mice bearing a TGF
      beta-negative esophageal tumor. Furthermore, administration of neutralizing anti
      TGF-beta antibody blocked the induction of Foxp3 in reconstituted Pan02-bearing
      Rag-/- mice. These results mimic earlier in vitro studies showing induction of
      Foxp3 through CD3 plus CD28 stimulation in the presence of TGF-beta. We conclude
      that Pan02 tumor promotes the prevalence of Treg, in part through the secretion
      of TGF-beta, which may result in immune evasion.

PMID- 16799338
TI  - B7.1/NHS76: a new costimulator fusion protein for the immunotherapy of solid
      tumors.
AB  - Tumor evasion from immune surveillance is due to the anergic status of tumor
      infiltrating lymphocytes, especially T cells. Inappropriate or absent expression
      of costimulatory molecules such as B7.1 and B7.2 lead to anergy and apoptosis of
      tumor-infiltrating T cells. To reverse this situation, a tumor-targeted fusion
      protein, human B7.1/NHS76, was generated by molecular engineering, which retains
      both the costimulatory activity of B7.1 and the tumor-targeting ability of NHS76
      antibody. NHS76 is a human tumor necrosis therapy monoclonal antibody derived
      from phage display, and is capable of binding intracellular antigens, which are
      accessible and abundant in necrotic regions of tumors. As human B7.1 can interact
      functionally with murine B7.1 counter-receptors, the immunotherapeutic potential
      of this fusion protein was tested in 3 mouse tumor models (Colon 26, RENCA, and
      MAD109), and animal studies showed a 35% to 55% reduction in tumor volume. To
      modulate the immune inhibitory microenvironment in tumors, naturally occurring
      CD4+ CD25+ Treg cells were depleted by cytotoxic CD4 or CD25 antibodies.
      Combination therapy with anti-Treg and B7.1/NHS76 produced complete regression of
      established tumors and was associated with increased effector T-cell infiltration
      in tumors. Rechallenge experiments performed 3 months after mice attained
      complete remission by combination therapy showed that immunologic memory was
      established by these treatments. These studies indicate that the targeting of
      B7.1 to necrotic areas of tumors, where both the release of tumor antigens and
      infiltrating lymphocytes are prevalent, may be a new approach for the
      immunotherapy of solid tumors. Our results also suggest that the manifestation of
      immune-inhibitory factors such as the presence of Treg cells at the tumor site
      and associated draining lymph nodes may be a major cause for immune system
      failure to eradicate solid tumors.

PMID- 16799339
TI  - Robust expansion of viral antigen-specific CD4+ and CD8+ T cells for adoptive T
      cell therapy using gene-modified activated T cells as antigen presenting cells.
AB  - Cytomegalovirus (CMV) reactivation after stem cell transplantation can be treated
      with CMV-specific T cells, but current in vitro techniques using dendritic cells
      as antigen-presenting cells are time-consuming and expensive. To simplify the
      production of clinical grade CMV-specific T cells, we evaluated gene-modified
      activated T cells [antigen presenting T cells (T-APCs)] as a reliable and easily
      produced source of APCs to boost CD4+ and CD8+ T-cell responses against the
      immunodominant CMV antigen pp65. T-APCs expressing the full-length immunodominant
      CMV pp65 gene were used to stimulate the expansion of autologous T cells. After
      10 to 14 days, the T cell lines were tested for antigen specificity by using the
      flow cytometric intracellular detection of interferon-gamma after stimulation for
      6 hours with a pp65 peptide library of 15-mers, overlapping by 11 amino acids.
      Under optimal conditions, this technique induced a median 766-fold and a 652-fold
      expansion of pp65-specific CD4+ and CD8+ responder cells, respectively, in 15 T
      cell lines. In 13 of 15 T cell lines, over 10 antigen-specific CD4+ plus CD8+ T
      cells were generated starting with only 5x10 peripheral blood mononuclear cells,
      representing an over 3-log increase. These data indicate that T-APCs efficiently
      boost pp65-specific CD4+ and CD8+ T cell numbers to clinically useful levels. The
      approach has the advantage of using a single leukocyte collection from the donor
      to generate large numbers of CMV-specific T cells within a total 3-week culture
      period using only one stimulation of antigen.

PMID- 16799340
TI  - A phase I study of an allogeneic cell vaccine (VACCIMEL) with GM-CSF in melanoma
      patients.
AB  - We investigated whether recombinant human granulocyte-monocyte-colony-stimulating
      factor (rhGM-CSF) increased the immunogenicity of VACCIMEL, a vaccine consisting
      of 3 irradiated allogeneic melanoma cell lines. A phase I clinical trial was
      performed on 20 melanoma patients in stages IIB (n=2), III (n=10), and IV (n=8),
      who were disease free after surgery (n=16) or had minimal disease (n=4). Cohorts
      of 4 patients were vaccinated 4 times with VACCIMEL and bacillus Calmette Guerin
      (BCG) as adjuvant. Besides, the patients received placebo (group 1) or GM-CSF:
      150 microg (group 2), 300 microg (group 3), 400 microg (group 4), and 600 microg
      (group 5) per vaccine. The combination of VACCIMEL and GM-CSF had low toxicity.
      Only in group 5, grade 2 thoracic pain (3/4 patients) and abdominal cramps (2/4
      patients) were observed. Delayed-type hypersensitivity increased after
      vaccination and it was highest in group 4. Phytohemagglutinin stimulation of
      peripheral blood lymphocytes was analyzed in 9 patients: 4/9 had normal
      stimulation; 3/9 had low basal stimulation, which recovered after vaccination;
      and 2/9 were not stimulated. Antimelanoma antibodies preexisted in 9/19 patients;
      in 3/19 patients, antibodies anti-33 kd, 90 kd, and 100 kd antigens were induced
      by vaccination. IgG2 but not IgG1 antibodies were detected. Anti-BCG antibodies,
      mostly IgG2, reached the highest post/prevaccination ratio in group 4. Median
      serum interleukin-12 was lower in progressing patients (61.6 pg/mL) than in those
      without evident disease (89 pg/mL). Thus, its low toxicity and the induction of a
      predominantly cellular immune response suggest that the addition of 300 to 400
      microg GM-CSF to VACCIMEL is useful in increasing the immune response.

PMID- 16799342
TI  - Comparison of different extubation techniques in lumbar surgery: prone extubation
      versus supine extubation with or without prior injection of intravenous
      lidocaine.
AB  - The aim of this study was to evaluate the incidence of coughing and breath
      holding in patients undergoing lumbar surgery extubated in prone position, supine
      position, or supine position with intravenous lidocaine before extubation. About
      105 ASA I to II patients undergoing lumbar surgery were extubated in prone
      position in group P (n = 35), in supine position in group S (n = 35) and in
      supine position with intravenous 1.5 mg/kg lidocaine 10 minutes before extubation
      in group SL (n = 35). The number of patients who coughed and demonstrated breath
      holding was noted at emergence period. The time of loss of monitoring while
      repositioning the patient was recorded. The frequency of cough in group S was
      higher compared with group P at 1 minute after extubation (P = 0.008). Two and
      three minutes after extubation, the patients in group S demonstrated higher cough
      incidence compared with groups P and SL (P < 0.05). The incidence of breath
      holding in the first 6 minutes was lower in group P (n = 11) compared with groups
      S (n = 29) and SL (n = 25)(P = 0.001). The loss of monitoring time was longer in
      groups S (62 +/- 40 s) and SL (53 +/- 39 s) when compared with group P (0 s) (P <
      0.01). Prone emergence and supine emergence with intravenous lidocaine provides
      an alternative approach to conventional supine emergence and prone extubation
      offers less cough and breath holding and continuation of monitoring.

PMID- 16799341
TI  - Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic
      melanoma.
AB  - We previously reported our experience in treating 56 patients with metastatic
      melanoma using a human anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody.
      Durable tumor regressions were seen that correlated with the induction of
      autoimmune toxicities. In this study, we treated 46 additional patients using an
      intrapatient dose escalation schema to test whether higher doses of anti-CTLA-4
      antibody would induce increased autoimmunity and concomitant tumor regression.
      Twenty-three patients started anti-CTLA-4 antibody administration at 3 mg/kg and
      23 patients started treatment at 5 mg/kg, receiving doses every 3 weeks. Patients
      were dose-escalated every other dose to a maximum of 9 mg/kg or until objective
      clinical responses or grade III/IV autoimmune toxicity were seen. Escalating
      doses of antibody resulted in proportionally higher plasma concentrations.
      Sixteen patients (35%) experienced a grade III/IV autoimmune toxicity. Five
      patients (11%) achieved an objective clinical response. Two of the responses are
      ongoing at 13 and 16 months, respectively. Flow cytometric analysis of peripheral
      blood revealed significant increases in both T-cell surface markers of activation
      and memory phenotype. Thus, higher serum levels and prolonged administration of
      anti-CTLA-4 antibody resulted in a trend toward a greater incidence of grade
      III/IV autoimmune toxicity than previously reported, but did not seem to increase
      objective response rates.

PMID- 16799343
TI  - Quantitation of ischemic events after severe traumatic brain injury in humans: a
      simple scoring system.
AB  - BACKGROUND: Cerebral ischemia is recognized as one of the most important
      mechanisms responsible for secondary brain damage following severe traumatic
      brain injury (TBI), contributing to an increased mortality and a worse neurologic
      outcome. METHOD: A simple 5-item scoring system, taking into account the
      occurrence of specific potentially brain-damaging events (hypoxemia, hypotension,
      low cerebral blood flow, herniation, and low cerebral perfusion pressure) has
      been tested in a large population of severe TBI patients. Aims of this
      retrospective study were to validate the ability of the proposed ischemic score
      to predict neurologic outcome and to correlate the ischemic score with the
      results of microdialysis-based neurochemical monitoring and brain tissue oxygen
      monitoring. FINDINGS: In a population of 172 severe TBI patients, a significant
      correlation was found between ischemic score and neurologic outcome, both at 3
      months (r = -0.32; P < 0.01) and at 6 months (r = -0.31; P < 0.01). Significant
      correlations were also found with the most important neurochemical analytes.
      CONCLUSIONS: The ischemic score proposed here, may be determined during the acute
      intensive care unit period, and correlates closely with outcome, which can only
      be determined 3 to 6 months, after injury. It also shows a correlation with
      neurochemical analytes.

PMID- 16799345
TI  - Cerebrovascular reactivity to carbon dioxide in the normal and abnormal cerebral
      hemispheres under anesthesia in patients with frontotemporal gliomas.
AB  - Cerebral pathology may alter the cerebrovascular reactivity to carbon dioxide
      (CO2). In the present study, in patients with brain tumors, we examined the
      cerebral vascular reactivity to CO2 in the cerebral hemispheres with and without
      tumors under intravenous and inhalational anesthesia. Twenty-nine patients
      undergoing craniotomy for frontotemporal gliomas were randomized to receive
      intravenous anesthesia with propofol or inhalational anesthesia with isoflurane.
      Cerebral blood flow velocity in the middle cerebral artery (VMCA) and pulsatality
      index were measured under normocapnia and hypocapnia in the normal cerebral
      hemisphere and the hemisphere with tumor. Hypocapnia significantly decreased the
      VMCA in both the cerebral hemispheres under both the anesthetic techniques (P <
      0.006). The percentage change in VMCA was similar between the hemispheres with
      and without tumor both under isoflurane (3.45 +/- 4.11% on the normal side and
      2.91 +/- 2.40% on the tumor side; mean difference 0.54 +/- 1.31%; 95% CI -2.18 to
      +3.27) and propofol anesthesia (2.32 +/- 2.64% on the normal side and 1.69 +/-
      4.04% on the tumor side; mean difference 0.63 +/- 1.2%; 95% CI -1.83 to +3.10).
      The changes in pulsatality index also were not significantly different between
      the hemispheres. In conclusion, cerebrovascular response to hypocapnia is similar
      between the normal and the abnormal cerebral hemispheres both under intravenous
      and inhalational anesthesia.

PMID- 16799344
TI  - A comparison of effects of alfentanil, fentanyl, and remifentanil on hemodynamic
      and respiratory parameters during stereotactic brain biopsy.
AB  - The aim of this study was to compare the effects of 3 different sedative
      analgesic regimens in patients with intracranial mass lesions undergoing
      stereotactic brain biopsy. A 135 outpatients with American Society of
      Anesthesiologists I to II were divided into 3 groups: group A (n = 45) received a
      loading dose of IV alfentanil 7.5 microg/kg followed by infusion rate of 0.25
      microg/kg/min; group F (n = 45) received a bolus dose of 1 microg/kg IV fentanyl
      and repeated as needed; and group R (n = 45) received infusion of 0.05
      microg/kg/min remifentanil. Target level of sedation was 3 to 4 of the Ramsay
      Sedation Scale. Systolic and diastolic blood pressure, heart rate, respiratory
      rate, peripheric oxygen saturation (SpO2), and end-tidal carbon dioxide were
      recorded at different stages of the procedures. The patients in group F had
      significantly lower mean heart rate than those in groups A and R, but this was
      not in the limits of the bradycardia. The patients in group A had significantly
      lower mean SpO2 than those in the other groups, but mean SpO2 values did not drop
      below 94%. There were no significant differences in end-tidal carbon dioxide and
      respiratory rate values among the groups. Our results suggest that all 3 regimens
      have relatively similar hemodynamic and respiratory responses. The use of bolus
      fentanyl technique caused less hemodynamic stability. The continuous infusion
      technique of remifentanil or alfentanil provided better control on hemodynamic
      parameters.

PMID- 16799346
TI  - Mild hypothermia promotes pro-inflammatory cytokine production in monocytes.
AB  - Hypothermia is often associated with compromised host defenses and infection.
      Deteriorations of immune functions related to hypothermia have been investigated,
      but the involvement of cytokines in host defense mechanisms and in infection
      remains unclear. We have previously shown that mild hypothermia modifies cytokine
      production by peripheral blood mononuclear cells. In this study, the effects of
      hypothermia on the monocytic production of several cytokines and nitric oxide
      (NO) were determined. Monocytes obtained from 10 healthy humans were cultured
      with lipopolysaccharide (LPS) under hypothermic (33 degrees C) or normothermic
      (37 degrees C) conditions for 48 hours. We performed flow cytometric analysis for
      simultaneous measurement of interleukin (IL)-8, IL-1beta, IL-6, IL-10, IL-12p70,
      and tumor necrosis factor (TNF)-alpha in culture supernatants. NO production was
      quantified as accumulation of nitrite in the medium by a colorimetric assay.
      Compared with normothermia, mild hypothermia raised the levels of IL-1beta, IL-6,
      IL-12p70, and TNF-alpha produced by monocytes stimulated with LPS. On calculating
      the ratios of these elevated cytokines to IL-10, however, only IL-12p70/IL-10 and
      TNF-alpha/IL-10 ratios were significantly elevated under hypothermic conditions.
      In contrast, hypothermia did not affect NO production. This study demonstrates
      that mild hypothermia affects the balance of cytokines produced by monocytes,
      leading to a pro-inflammatory state. Specifically, monocytic IL-12 and TNF-alpha
      appear to be involved in the immune alterations observed in mild hypothermia.
      However, the clinical significance of these phenomena remains to be clarified.

PMID- 16799347
TI  - Effects of pneumoperitoneum and LPS-induced endotoxemia on cerebral perfusion
      pressure in pigs.
AB  - Multitrauma patients commonly develop abdominal compartment syndrome, which is
      defined as the end result of sustained, uncorrected, intra-abdominal
      hypertension. We aimed to assess the effects of increased intra-abdominal
      pressure (IAP) upon intracranial pressure (ICP) and cerebral perfusion pressure
      (CPP) in the presence or absence of lipopolysacharide (LPS)-induced endotoxemia
      using an experimental porcine model of pneumoperitoneum. Experimental procedures
      were approved by the Animal Care Review Committee of the National Veterinary
      Institute. Sixteen female pigs weighing 20 to 25 kg, aged 3 to 4 months were
      used. The animal model of increased IAP employed in our studies was produced with
      intraperitoneal administration of helium at 25 mm Hg under general anesthesia.
      After induction of pneumoperitoneum, 16 animals were randomly divided into 2
      groups of 8 pigs each. One group received LPS intravenously (endotoxin group) and
      the second group received saline (control group). ICP, CPP, and hemodynamic
      variables were continuously monitored and recorded. A significant reduction of
      the cardiac output and concurrent increases in systemic vascular resistance and
      central venous pressure were observed in both groups after induction of
      pneumoperitoneum. ICP increased whereas CPP decreased significantly compared with
      baseline values in both groups after elevation of IAP. After LPS administration
      (endotoxin group), the cardiac output and mean arterial pressure decreased
      significantly. The CPP decreased further in the endotoxin group after LPS
      administration, whereas ICP remained unchanged. IAP increases produce significant
      increases in the ICP and decreases in the CPP in this animal model. LPS-induced
      endotoxemia further decreased CPP.

PMID- 16799348
TI  - Increased lactate levels impair the coagulation system--a potential contributing
      factor to progressive hemorrhage after traumatic brain injury.
AB  - Progressive intracerebral contusions are a major problem in the management of
      patients with severe traumatic brain injury that is also linked to worse outcome.
      Microdialysis studies have revealed that lactate levels are very high inside
      contusions, corresponding to significant acidosis. The current study was
      performed in an effort to investigate whether the lactate accumulation inside
      cerebral contusions may be a contributing factor to the prolonged bleeding inside
      contusions. We have investigated the effects of lactic acidosis on the
      coagulation system with rotational thromboelastometry. It was a laboratory study
      involving 6 healthy volunteers. Blood was drawn and the pH was adjusted by
      addition of lactic acid in vitro. The pH levels studied were 7.4, 7.2, 7.0, and
      6.8. The pH was also readjusted to 7.4 by addition the buffer THAM to blood
      initially adjusted to a pH of 6.8 to study the reversibility of potential adverse
      effects induced by the lactic acidosis. We found the coagulation to be
      significantly impaired by lactic acidosis (P = 0.000l). The impairment found was
      reversible after correction of the acidosis by a buffer. In conclusion, we found
      that lactic acidosis impaired the coagulation system. The impairment caused by
      lactic acidosis may be one factor causing the progressive hemorrhage in
      posttraumatic cerebral contusions, known to have high levels of lactate and
      correspondingly low pH. It may also be important to consider in bleeding trauma
      patients.

PMID- 16799349
TI  - Bispectral index and spectral entropy in neuroanesthesia.
AB  - Spectral Entropy (SpEn) is an alternative tool to the bispectral index (BIS) for
      monitoring depth of hypnosis. SpEn measures response entropy (RE) and state
      entropy (SE). This open-label prospective study was designed to evaluate SpEn and
      BIS in 20 patients undergoing elective supratentorial neurosurgery with
      craniotomy and resection of brain tumors. SpEn and BIS were obtained continuously
      by Datex Ohmeda M-entropy module S/5 (Helsinki, Finland) and Aspect Medical
      System BIS (Newton), respectively. Total intravenous anesthesia was performed in
      all patients by Fresenius Vial infusion system (Brezins, France) to maintain a
      plasma concentration of propofol of 2.5 to 5 microg mL(-1) and sufentanil of 0.2
      to 0.4 etag mL(-1). SpEn, BIS, the estimated propofol effect-site concentrations
      (Ce), the mean arterial pressure (MAP), and the heart rate (HR) were recorded
      during 12 specific events: induction of anesthesia, patient stop counting, loss
      of blinking reflex, intubation, mayfield pinning, craniotomy, termination of
      propofol infusion, recovery of blinking reflex, coughing, limb movement, order
      execution, and extubation. Stated that prediction probability or P(K) represents
      an indicator probability to predict correctly the rank order of an arbitrary pair
      of distinct observed indices of depth of hypnosis (ie, clinical settings and SpEn
      indices, or BIS, Ce, MAP, HR), PK of BIS, SE, RE, and Ce provided a better depth
      of hypnosis than MAP and HR; RE being the best for rapidity, SE for sensitivity,
      and BIS for specificity. There is good correlation between the 3 hypnosis indices
      and Ce. This study demonstrates that SpEn provides a reproducible hypnosis index
      for patients undergoing supratentorial neurosurgical procedures.

PMID- 16799350
TI  - Intraoperative motor-evoked potential monitoring in scoliosis surgery: comparison
      of desflurane/nitrous oxide with propofol total intravenous anesthetic regimens.
AB  - STUDY DESIGN: A prospective, randomized study in a large general hospital
      setting. BACKGROUND: During spinal surgery, monitoring motor-evoked potentials
      (MEPs) is a means of assessing the intraoperative integrity of corticospinal
      pathways. However, MEPs are known to be sensitive to the effects of anesthetic
      agents. OBJECTIVE: To compare the use of desflurane or total intravenous
      anesthetic regimens (TIVA) with multipulse cortical stimulation for
      intraoperative monitoring (IOM). METHODS: Twenty consecutive patients (10 in each
      arm) undergoing scoliosis correction surgery were randomly assigned to 2 equal
      groups receiving desflurane or TIVA. Inhalational anesthesia was maintained using
      66% nitrous oxide in oxygen and a mean end-tidal desflurane concentration of
      3.4%. For TIVA, continuous intravenous infusion of propofol was used. For
      analgesia, fentanyl and morphine were given when required for both groups.
      Cortical stimulation was achieved with 2 bipolar direct current stimulators
      connected in parallel by jumper cables. Five equivalent pulses 0.5 ms in duration
      at 4 ms intervals were delivered at C1C2 positions. MEP recordings were made in
      the abductor hallucis (AH) and tibialis anterior (TA) with needle electrodes.
      RESULTS: Reproducible MEPs were obtained throughout the operation in all 20
      cases, with up to 80 mA per stimulator. Before insertion of pedicle screws, mean
      MEP amplitudes (SD) obtained were 85 (19) and 21.7 (10.8) mV for AH and TA,
      respectively, using desflurane. With TIVA, amplitudes were 56.7 (28.4) and 59.1
      (24.5) mV, respectively. Both muscle MEP amplitudes were significantly different
      using different anesthetic regimens (P < 0.05 for all). AH MEP amplitudes
      obtained with desflurane were significantly larger than TA amplitudes (P <
      0.0001). No complications were reported intraoperatively and postoperatively.
      CONCLUSIONS: This is the first study comparing the use of desflurane and TIVA
      showing that both anesthetic regimens allowed successful intraoperative
      monitoring useage throughout the procedures. For MEP recording, the AH was the
      preferred muscle with a desflurane anesthetic regimen.

PMID- 16799353
TI  - Profound hypotension after intracisternal papaverine.

PMID- 16799354
TI  - Whither quality of breast cancer care?

PMID- 16799355
TI  - Correlates of between-surgeon variation in breast cancer treatments.
AB  - BACKGROUND: Determinants of between-surgeon variation in breast cancer treatment
      utilization are not well understood. OBJECTIVES: The objectives of this study
      were to evaluate variation in receipt of surgical treatment (ie, mastectomy or
      breast-conserving surgery with or without radiation) for women with stage I, II,
      or III breast cancer and receipt of breast reconstruction attributable to
      surgeons, and to assess factors associated with this between-surgeon variation.
      METHODS: We surveyed all attending surgeons (n = 456) of a population-based
      sample of patients with breast cancer diagnosed in Detroit and Los Angeles during
      2002 (n = 1844). Our analytic dataset linked data from 1477 patients with that of
      311 surgeons. We used random-effects modeling to account for the multilevel
      dataset and evaluated 2 outcomes: 1) primary surgical treatment (mastectomy vs.
      BCS); and 2) receipt of reconstruction before being surveyed (yes vs. no).
      Independent variables included patient-related factors (clinical and
      demographic), surgeon-related factors (breast procedure volume, practice setting,
      and demographics), surgeon treatment recommendation, and referral propensity.
      RESULTS: Surgeons explain some variation in use of both mastectomy and
      reconstruction (9.9% and 26%, respectively). Patient clinical factors and surgeon
      volume together explain approximately one-third of the between-surgeon variation
      in mastectomy. Patient factors and surgeon demographics explain approximately 60%
      of between-surgeon variation in reconstruction, and surgeon referral propensity
      explains an additional 15%. CONCLUSION: Our findings suggest that similar
      patients may get different treatment depending on their surgeon. Broader
      dissemination of guidelines coupled with increasing patient access to
      consultations before definitive surgery may reduce between-surgeon variation.
      Contributing factors such as patient-physician communication should be explored.

PMID- 16799357
TI  - Performance of International Classification Of Diseases, 9th Revision, Clinical
      Modification codes as an adverse drug event surveillance system.
AB  - BACKGROUND: Adverse drug events (ADEs) are one of the most frequent causes of
      iatrogenic injury. Because International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9-CM) codes are routinely assigned to
      inpatient discharges, they could provide a method to detect ADEs within a
      hospital, a state, and the nation. OBJECTIVE: The objective of this study was to
      determine validity of selected ICD-9-CM codes in identifying inpatient ADEs.
      RESEARCH DESIGN: An expert panel identified 416 ICD-9-CM codes to represent ADEs
      (flagged ADE codes). Retrospective chart review using a structured tool was
      performed to ascertain code performance in detecting ADEs. SUBJECTS: Subjects
      included 3103 inpatients from all 41 acute care hospitals in Utah in 2001: 1961
      inpatients sampled randomly (random sample) and 1142 inpatients sampled from the
      discharge records with at least one flagged ADE code (flagged sample). MEASURES:
      Measures were ADEs identified by structured review. RESULTS: The flagged sample
      yielded 1122 flagged ADE codes recorded in patient charts with 704 representing
      ADEs (63%). Two hundred eighty-six of the 704 verified ADE codes (41%) were
      determined to be inpatient ADEs. In the random sample, 32 of 58 ADEs (55%)
      causing hospital admission were detected by the ADE-flagged codes. Only 23 of 224
      inpatient ADEs had been assigned a flagged ADE code (10%). CONCLUSIONS: Flagged
      ADE codes have an overall positive predictive value of 63% and detect just over
      half of ADEs causing hospital admission. These codes have a positive predictive
      value of 25% for inpatient ADEs but detect only 10% of overall inpatient ADEs.
      Flagged ADE codes provide an imperfect but immediately available ADE surveillance
      system.

PMID- 16799356
TI  - Improving antibiotic selection: a systematic review and quantitative analysis of
      quality improvement strategies.
AB  - OBJECTIVE: We sought to assess which interventions are most effective at
      improving the prescribing of recommended antibiotics for acute outpatient
      infections. DESIGN AND METHODS: We undertook a systematic review with
      quantitative analysis of the Cochrane Registry Effective Practice and
      Organization of Care (EPOC) database, supplemented by MEDLINE and hand-searches.
      Inclusion criteria included clinical trials with contemporaneous or strict
      historical controls that reported data on antibiotic selection in acute
      outpatient infections. The effect size of studies with different intervention
      types were compared using nonparametric statistics. To maximize comparability
      between studies, quantitative analysis was restricted to studies that reported
      absolute changes in the amount of or percent compliance with recommended
      antibiotic prescribing. RESULTS: Twenty-six studies reporting 33 trials met
      inclusion criteria. Most interventions used clinician education alone or in
      combination with audit and feedback. Among the 22 comparisons amenable to
      quantitative analysis, recommended antibiotic prescribing improved by a median of
      10.6% (interquartile range [IQR] 3.4-18.2%). Trials evaluating clinician
      education alone reported larger effects than interventions combining clinician
      education with audit and feedback (median effect size 13.9% [IQR 8.6-21.6%] vs.
      3.4% [IQR 1.8-9.7%], P = 0.03). This result was confounded by trial sample size,
      as trials having a smaller number of participating clinicians reported larger
      effects and were more likely to use clinician education alone. Active forms of
      education, sustained interventions, and other features traditionally associated
      with successful quality improvement interventions were not associated with effect
      size and showed no evidence of confounding the association between clinician
      education-only strategies and outcome. CONCLUSIONS: Multidimensional
      interventions using audit and feedback to improve antibiotic selection were less
      effective than interventions using clinician education alone. Although
      confounding may partially account for this finding, our results suggest that
      enhancing the intensity of a focused intervention may be preferable to a less
      intense, multidimensional approach.

PMID- 16799358
TI  - Geographic diversity of low-volume hospitals in total knee replacement:
      implications for regionalization policies.
AB  - BACKGROUND/OBJECTIVES: Centers performing low volumes of total knee replacements
      (TKR) have worse outcomes of TKR than higher volume centers. Regionalization
      policies that shift patients to higher volume centers are being considered as a
      means of improving TKR outcomes. We sought to describe geographic diversity in
      the distribution of low-volume centers and examine state level characteristics
      associated with states that have a higher proportion of low-volume centers and/or
      a higher proportion of TKRs performed in low-volume centers. METHODS: We used
      U.S. Census data and geocoded Medicare claims to ascertain state-level
      demographic factors, procedure volume, and TKR rates and to conduct our state
      level analysis. We defined 2 outcomes: 1) proportion of all hospitals with a low
      annual TKR volume (<26 per year in the Medicare population); and 2) proportion of
      all TKRs in the Medicare population performed in low-volume centers. We examined
      linear associations among the 2 outcomes and state factors, and used multivariate
      regression to identify factors associated independently with these outcomes.
      RESULTS: Half of hospitals performing TKR in the Medicare population were low
      volume centers, accounting for 13% of TKRs. Multivariate analysis revealed lower
      TKR rates, higher proportion of rural areas and larger state area were associated
      with a higher proportion of low-volume hospitals in a state. Lower proportion of
      elderly residents, higher population density and higher proportion of rural areas
      predicted a higher proportion of TKRs performed in low-volume centers.
      CONCLUSIONS: The distribution of low-volume hospitals among U.S. states varies
      substantially. Regionalization of TKR may require different strategies in states
      with small and large numbers of low-volume centers.

PMID- 16799359
TI  - Quality improvement strategies for hypertension management: a systematic review.
AB  - BACKGROUND: Care remains suboptimal for many patients with hypertension. PURPOSE:
      The purpose of this study was to assess the effectiveness of quality improvement
      (QI) strategies in lowering blood pressure. DATA SOURCES: MEDLINE, Cochrane
      databases, and article bibliographies were searched for this study. STUDY
      SELECTION: Trials, controlled before-after studies, and interrupted time series
      evaluating QI interventions targeting hypertension control and reporting blood
      pressure outcomes were studied. DATA EXTRACTION: Two reviewers abstracted data
      and classified QI strategies into categories: provider education, provider
      reminders, facilitated relay of clinical information, patient education, self
      management, patient reminders, audit and feedback, team change, or financial
      incentives were extracted. DATA SYNTHESIS: Forty-four articles reporting 57
      comparisons underwent quantitative analysis. Patients in the intervention groups
      experienced median reductions in systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) that were 4.5 mm Hg (interquartile range [IQR]: 1.5 to 11.0)
      and 2.1 mm Hg (IQR: -0.2 to 5.0) greater than observed for control patients.
      Median increases in the percentage of individuals achieving target goals for SBP
      and DBP were 16.2% (IQR: 10.3 to 32.2) and 6.0% (IQR: 1.5 to 17.5). Interventions
      that included team change as a QI strategy were associated with the largest
      reductions in blood pressure outcomes. All team change studies included
      assignment of some responsibilities to a health professional other than the
      patient's physician. LIMITATIONS: Not all QI strategies have been assessed
      equally, which limits the power to compare differences in effects between
      strategies. CONCLUSION: QI strategies are associated with improved hypertension
      control. A focus on hypertension by someone in addition to the patient's
      physician was associated with substantial improvement. Future research should
      examine the contributions of individual QI strategies and their relative costs.

PMID- 16799360
TI  - Prior authorization policies for selective cyclooxygenase-2 inhibitors in
      Medicaid: a policy review.
AB  - BACKGROUND: Many state Medicaid programs use prior authorization programs to
      limit spending on cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs
      (coxibs). However, the evidence base for the prior authorization criteria has not
      been examined previously. METHODS: We determined whether prior authorization was
      required for coxibs in state Medicaid programs and collected data on what precise
      criteria needed to be met for a coxib prescription to be authorized. Prior
      authorization criteria were compared to clinical evidence regarding which
      patients are most likely to benefit from coxibs. RESULTS: By mid-2004, 35 states
      had implemented prior authorization requirements for coxibs. Of 5 major clinical
      factors that identify patients likely to benefit from coxibs, 18 states (51%)
      included all 5 factors and 9 states (26%) included 2 or fewer. Most states
      (33/35; 94%) required a previous trial of nonselective nonsteroidal anti
      inflammatory drugs before a coxib would be authorized. Several prior
      authorization programs included factors that had no connection to the clinical
      evidence. CONCLUSIONS: State Medicaid prior authorization policies for coxibs are
      heterogeneous in terms both of the criteria required to obtain a coxib and of the
      relationship of those criteria to clinical evidence. Development of clinically
      rational prescription drug policies should be a goal for all health insurers and
      represents an important priority for Medicare's prescription drug benefit
      program.

PMID- 16799362
TI  - The effects of managed care and competition on community-based clinical research.
AB  - BACKGROUND: The National Institutes of Health is developing practice-based
      clinical research networks (PBRNs) to expedite the pace of scientific discovery
      and improve care quality. Anecdotal evidence suggests managed care penetration
      and provider competition negatively affect PBRN clinical research. OBJECTIVE: The
      objective of this study is to examine the effects of environmental factors on
      clinical research performance in the National Cancer Institute's Community
      Clinical Oncology Program (CCOP). RESEARCH DESIGN: This study examined 49 CCOPs
      in 34 states using longitudinal (1991-2001) generalized least-squares regression
      including fixed effects, using secondary data from the National Cancer Institute,
      Group Health Association of America, InterStudy, American Hospital Association,
      Area Resource Files, and the Current Population Survey. MEASURES: Performance was
      measured as CCOP-level accrual in treatment trials, cancer prevention and control
      (CP/C) trials, and all trials combined. HMO penetration served as a proxy for
      managed care penetration. Competition measures included both hospital competition
      and physician competition. RESULTS: Managed care penetration was positively
      associated with accrual in areas of low to moderate penetration and negative in
      the areas of high penetration. Compared with areas with 5% penetration, areas
      with 15% penetration had 21% more treatment accrual and 66% more CP/C accrual.
      Compared with areas with 40% penetration, areas with 50% penetration had 11%
      lower treatment accrual and 3% lower CP/C accrual. CP/C accrual was more
      positively affected than treatment accrual. Greater hospital competition was
      associated with a decline in trial enrollment. CONCLUSIONS: The healthcare
      environment appears to have a significant effect on accrual into community-based
      cancer treatment and CP/C clinical trials. Findings for treatment and CP/C
      accrual suggest each type of accrual is distinct and requires different
      strategies and administrative methods.

PMID- 16799361
TI  - Ranking hospitals according to acute myocardial infarction mortality: should
      transfers be included?
AB  - OBJECTIVE: The objective of this population-based observational cohort study was
      to estimate the extent to which the inclusion/exclusion of transferred patients
      with acute myocardial infarction (AMI) impacts on hospital performance rankings.
      SUBJECTS: The authors studied 91,633 adult patients admitted to 116 acute care
      hospitals in Quebec, Canada, with a primary diagnosis of AMI between 1992 and
      1999. MAIN OUTCOME MEASURE: Hospital performance ranks, based on 30-day AMI
      mortality rates, were estimated with hierarchical models and compared using 3
      different methods for handling transferred patients (exclude all transfers;
      include transfers and assign outcome to the referring hospital; include transfers
      and assign outcome to the receiving hospital). The explanatory variable of
      interest was the hospital to which the patient's outcome was attributed. RESULTS:
      Using the 3 methods, 4 hospitals were ranked "best performers" once, and 1
      hospital ranked among the best in 2 of the 3 analyses performed. Nine hospitals
      were ranked "worst performers" at least once (4 of which ranked among the "worst"
      once only, 2 ranked among the "worst" twice, and 3 were consistently ranked
      "worst performers" in all analyses). There was significant variation in mortality
      rates among hospitals, and the difference in the rates between the highest and
      lowest ranking hospitals exceeded the clinically relevant benchmark of 1%.
      CONCLUSIONS: Performance evaluation studies that compare hospital mortality rates
      typically exclude transferred patients. However, methods used to deal with AMI
      patient transfers influenced hospital ranks when comparing 30-day mortality
      rates. Excluding transfers may lead to an inaccurate depiction of the quality of
      healthcare services in regionalized healthcare systems that call for the timely
      interhospital transfer of patients with AMI.

PMID- 16799363
TI  - Do longer delays for coronary artery bypass surgery contribute to preoperative
      mortality in less urgent patients?
AB  - BACKGROUND: Priority wait lists are common for managing access to cardiac surgery
      in publicly funded health systems. We evaluated whether longer delays contribute
      to the probability of death before surgery among patients prioritized into the
      less urgent category. METHODS: We studied records of 9233 patients registered for
      isolated coronary artery bypass graft (CABG) in British Columbia, Canada. The
      primary outcome was death before surgery. We estimated the probability that a
      patient, who could be removed from the list as a result of surgery, death, or
      other competing events, dies on or before a certain wait-list week. RESULTS:
      Despite similar death rates in semiurgent and nonurgent groups, 0.63 (95%
      confidence interval, 0.46-0.80) versus 0.58 (0.36-0.80) per 1000 patient-weeks,
      nonurgent patients were remaining on the list longer, which contributed to higher
      cumulative incidence of all-cause death than in semiurgent group (adjusted odds
      ratio = 1.66; 1.03-2.68). By 52 weeks on the wait list, 0.9% (0.6-1.1) and 1.3%
      (0.8-1.8) of patients died in semiurgent and nonurgent groups, respectively (P <
      0.01). Similar proportions of deaths related to cardiovascular disease estimated
      over wait-list time in both groups (P = 0.40) were the result of shorter delays
      in the semiurgent group despite a higher rate of death resulting from
      cardiovascular disease (0.50 [0.36-0.65] vs. 0.34 [0.17-0.51] per 1000 patient
      weeks). CONCLUSION: Queuing according to urgency of treatment contributed to a
      higher proportion of CABG candidates dying before surgery from all causes in the
      nonurgent compared with the semiurgent group despite similar weekly death rates
      observed in both groups. However, similar probabilities of death resulting from
      cardiovascular disease observed in both groups over wait-list time were the
      result of shorter delays in the semiurgent group despite a higher rate of
      cardiovascular death.

PMID- 16799364
TI  - Administrative versus clinical data for coronary artery bypass graft surgery
      report cards: the view from California.
AB  - OBJECTIVE: The objective of this study was to compare the performance of a risk
      model for isolated coronary artery bypass graft (CABG) surgery based on
      administrative data with that of a clinical risk model in predicting mortality
      and identifying hospital performance outliers. METHODS: Clinical data records
      from the California CABG Mortality Reporting Program for 38,230 isolated CABG
      patients undergoing surgery in 2000-2001 were linked to records in the California
      patient discharge data (PDD) abstract. Risk factors based on administrative data
      that mirrored clinical risk factors were developed using the condition present at
      admission indicator in the PDD to separate preoperative acute conditions from
      complications of surgery. Using logistic regression, risk model performance
      across data sources was compared along with hospital risk-adjusted mortality
      ranks and quality ratings. RESULTS: The administrative data showed lower
      prevalence of risk factors when compared with the clinical data. The clinical
      risk model had somewhat better discrimination (C = 0.824) than the administrative
      model (C = 0.799). The clinical model yielded 17 outliers and the administrative
      model 16 with agreement on 12 hospitals' status. Performance of the
      administrative risk model was minimally affected by removal of information from
      prior admissions and removal of risk factors not confirmed in the clinical
      record. CONCLUSIONS: Unique properties of the California administrative data,
      including the ability to distinguish acute preoperative risk factors from
      complications of surgery, permitted construction of an administrative risk model
      that predicts mortality on par with most published clinical models. Despite this,
      the administrative model identified slightly different hospital outliers, which
      may indicate somewhat biased assessments of hospital patient risk.

PMID- 16799365
TI  - Recruiting minority primary care practices into practice-based research.
AB  - BACKGROUND: A potentially fruitful strategy for increasing enrollment of minority
      patients in research is to engage minority clinicians. However, little attention
      has been paid to unique challenges and effective strategies for engaging
      practices with minority physicians. OBJECTIVE: The objective of this study was to
      provide a model for recruiting community-based primary care practices with
      minority physicians into research studies. RESEARCH DESIGN: Practices were
      recruited using a 3-step process that included telephone contact, on-site
      meetings, and follow-up discussions. Strategies used to recruit 18 New Jersey
      community-based primary care practices with minority physicians for a quality
      improvement intervention study were assessed. RESULTS: Twelve of 18 practices
      (67%) were successfully recruited into the study. Effective recruitment
      strategies included building rapport using a multiethnic/multidisciplinary team
      led by a minority physician recruiter and stressing study benefits for the
      practice. We attempted to match recruiters and key practice members by race,
      underrepresented minority status of the lead recruiter, gender, career stage,
      experience in urban practice, and experience in clinical instruction. Practices
      that were successfully recruited had more characteristics in common between
      recruiters and key practice members than unsuccessfully recruited practices (mean
      number of characteristic matches = 3.75 vs. 1.83, P = 0.020). Study benefits
      cited by participants as motivators for participation included a general desire
      to provide good patient care by understanding their practices' strengths and
      challenges (92%) and improving their practice (85%). CONCLUSIONS: Our experience
      suggests that a staged, tailored, and iterative recruitment process emphasizing
      communication and relationship building can be successful in recruiting community
      based primary care minority physicians into practice-based research.

PMID- 16799367
TI  - Response to an article in the October 2005 issue of Medical Care.

PMID- 16799371
TI  - A brief history of wound care.
AB  - Since the caveman, man has been tending to his wounds. Wound care evolved from
      magical incantations, potions, and ointments, to a systematic text of wound care
      and surgery from Hippocrates and Celsus. These advances were lost after the fall
      of the Roman Empire. In Europe, the Middle Ages were a regression of wound care
      back to potions and charms. It was'nt until the time of large armies using
      muskets and cannons that surgical wound care emerged again. This article will
      briefly highlight major milestones in wound care.

PMID- 16799372
TI  - The basic science of wound healing.
AB  - Understanding wound healing today involves much more than simply stating that
      there are three phases: "inflammation, proliferation, and maturation." Wound
      healing is a complex series of reactions and interactions among cells and
      "mediators." Each year, new mediators are discovered and our understanding of
      inflammatory mediators and cellular interactions grows. This article will attempt
      to provide a concise report of the current literature on wound healing by first
      reviewing the phases of wound healing followed by "the players" of wound healing:
      inflammatory mediators (cytokines, growth factors, proteases, eicosanoids,
      kinins, and more), nitric oxide, and the cellular elements. The discussion will
      end with a pictorial essay summarizing the wound-healing process.

PMID- 16799373
TI  - Chronic wound pathogenesis and current treatment strategies: a unifying
      hypothesis.
AB  - Most chronic wounds can be classified into three major types: pressure ulcers,
      venous ulcers, and diabetic ulcers. The authors propose a unifying hypothesis of
      chronic wound pathogenesis based on four main causative factors: local tissue
      hypoxia, bacterial colonization of the wound, repetitive ischemia-reperfusion
      injury, and an altered cellular and systemic stress response in the aged patient.
      Traditional strategies for the treatment of chronic wounds have shown limited
      success. The authors explore potential treatment regimens specifically aimed at
      each individual determinant of chronic wound pathogenesis. Furthermore, they
      explore a combined therapeutic approach that collectively targets all the
      components of chronic wound pathology. These innovative ideas and therapies could
      be of substantial interest for clinicians and researchers, while further offering
      significant benefit to patients with chronic wounds.

PMID- 16799374
TI  - Nutrition and wound healing.
AB  - The relationship between nutrition and wound healing--after injury or surgical
      intervention--has been recognized for centuries. There is no doubt that adequate
      carbohydrate, fat, and protein intake is required for healing to take place, but
      research in the laboratory has suggested that other specific nutritional
      interventions can have significant beneficial effects on wound healing.
      Successful translation into the clinical arena, however, has been rare. A review
      of normal metabolism as it relates to wound healing in normoglycemic and diabetic
      individuals is presented. This is followed by an assessment of the current
      literature and the data that support and refute the use of specialized
      nutritional support in postoperative and wounded patients. The experimental
      evidence for the use of arginine, glutamine, vitamins, and micronutrient
      supplementation is described. Most of the experimental evidence in the field
      supporting the use of specialized nutritional support has not been borne out by
      clinical investigation. A summary of the clinical implications of the data is
      presented, with the acknowledgment that each patient's plan of care must be
      individualized to optimize the relationship between nutrition and wound healing.

PMID- 16799375
TI  - Using physiology to improve surgical wound outcomes.
AB  - Despite major advances in surgical management and approaches, including aseptic
      techniques, prophylactic antibiotics, and laparoscopic surgery, surgical wound
      infection and wound failure remain common complications of surgery. In a review
      of the literature, the authors found that a growing body of literature supports
      the concept that patient factors are a major determinant of wound outcome after
      surgery. In particular, wounds are exquisitely sensitive to hypoxia, which is
      both common and preventable. Perioperative management can be adapted to promote
      postoperative wound healing and resistance to infection. The most important
      factors are fluid management, temperature management, pain control, increased
      arterial oxygen tension, and, as has been long recognized, appropriate sterile
      techniques and administration of prophylactic antibiotics. This article reviews
      how knowledge of and attention to physiology can improve quality of care in both
      acute and chronic wounds.

PMID- 16799376
TI  - Clinical approach to wounds: debridement and wound bed preparation including the
      use of dressings and wound-healing adjuvants.
AB  - This is a clinical review of current techniques in wound bed preparation found to
      be effective in assisting the wound-healing process. The process begins with the
      identification of a correct diagnosis of the wound's etiology and continues with
      optimizing the patient's medical condition, including blood flow to the wound
      site. Debridement as the basis of most wound-healing strategies is then
      emphasized. Various debridement techniques, including surgery, topical agents,
      and biosurgery, are thoroughly discussed and illustrated. Wound dressings,
      including the use of negative pressure wound therapy, are then reviewed. To
      properly determine the timing of advance therapeutic intervention, the wound
      healing progress needs to be monitored carefully with weekly measurements. A
      reduction in wound area of 10 to 15 percent per week represents normal healing
      and does not mandate a change in the current wound-healing strategy. However, if
      this level of wound area reduction is not met consistently on a weekly basis,
      then alternative healing interventions should be considered. There is a growing
      body of evidence that can provide guidance on the appropriate use of such
      adjuvants in the problem wound. Several adjuvants are discussed, including growth
      factor, bioengineered tissues, and hyperbaric medicine.

PMID- 16799377
TI  - Effect of different wound dressings on cell viability and proliferation.
AB  - BACKGROUND: Many new dressings have been developed since the early 1980s. Wound
      healing comprises cleansing, granulation/vascularization, and epithelialization
      phases. An optimum microenvironment and the absence of cytotoxic factors are
      essential for epithelialization. This study examines the effect of extracts of
      different wound dressings on keratinocyte survival and proliferation. METHODS:
      Keratinocyte cultures were exposed for 40 hours to at least three extracts of
      each of the following wound dressings, which were tested in octuplicate:
      Acticoat, Aquacel-Ag, Aquacel, Algisite M, Avance, Comfeel Plus transparent,
      Contreet-H, Hydrasorb, and SeaSorb. Silicone extract provided the reference
      material. Controls were included of cells cultured in medium that had been
      incubated under conditions identical to those used with the extracts. Cell
      survival (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction)
      and proliferation (5-bromo-2':-deoxyuridine incorporation) were measured.
      RESULTS: Extracts of silver-containing dressings (Acticoat, Aquacel-Ag, Contreet
      H, and Avance) were most cytotoxic. Extracts of Hydrasorb were less cytotoxic but
      markedly affected keratinocyte proliferation and morphology. Extracts of alginate
      containing dressings (Algisite M, SeaSorb, and Contreet-H) demonstrated high
      calcium concentrations, markedly reduced keratinocyte proliferation, and affected
      keratinocyte morphology. Extracts of Aquacel and Comfeel Plus transparent induced
      small but significant inhibition of keratinocyte proliferation. CONCLUSIONS: The
      principle of minimizing harm should be applied to the choice of wound dressing.
      Silver-based dressings are cytotoxic and should not be used in the absence of
      infection. Alginate dressings with high calcium content affect keratinocyte
      proliferation probably by triggering terminal differentiation of keratinocytes.
      Such dressings should be used with caution in cases in which keratinocyte
      proliferation is essential. All dressings should be tested in vitro before
      clinical application.

PMID- 16799380
TI  - Vacuum-assisted closure: state of clinic art.
AB  - Treatment of wounds has been the cornerstone of plastic surgery since its
      inception. Vacuum-assisted closure provides a new paradigm that can be used in
      concert with a wide variety of standard existing plastic surgery techniques. It
      was originally developed as an alternative treatment for debilitated patients
      with chronic wounds. It has rapidly evolved into a widely accepted treatment of
      chronic and acute wounds, contaminated wounds, burns, envenomations,
      infiltrations, and wound complications from failed operations. The ease of
      technique and a high rate of success have encouraged its adaptation by thoracic,
      general, trauma, burn, orthopedic, urologic, as well as plastic surgeons. This
      article discusses multidisciplinary advances in the use of the vacuum-assisted
      closure technique over the past 10 years and its status as of 2006. Creative
      surgeons continue to regularly adapt the system to difficult problems. This
      technique in trained surgical hands greatly enhances the scope and safety of
      wound treatment.

PMID- 16799379
TI  - Vacuum-assisted closure: state of basic research and physiologic foundation.
AB  - A tremendous amount of research has been conducted in recent years investigating
      the mechanisms of action by which the application of subatmospheric pressure to
      wounds increases the rate of healing. Similarly, numerous studies have also been
      conducted examining the physiologic response of wounds to the applied
      subatmospheric pressure. However, many more need to be conducted. A series of
      basic studies examining the use of subatmospheric pressure to treat wounds is
      presented, including the original studies upon which the vacuum-assisted closure
      device was based (on blood flow, granulation tissue formation, bacterial
      clearance, and survival of random-pattern pedicle flaps). Subsequent studies
      analyzing removed fluids, envenomation/extravasation, burns, grafts, and in vitro
      tissue culture studies are also reviewed. Two broad mechanisms of action are
      proposed: removal of fluid and mechanical deformation. Fluid removal both
      decreases edema--thus decreasing interstitial pressure and shortening distances
      of diffusion--and removes soluble factors that may affect the healing process
      (both positively and negatively). The relationship of mechanical deformation to
      increased growth is well known to plastic surgeons, as it is the basis of tissue
      expansion. While much has been done, a great deal more needs to be done to
      elucidate the mechanisms of action responsible for the dramatic response seen
      clinically.

PMID- 16799381
TI  - Clinical evaluation of recombinant human platelet-derived growth factor for the
      treatment of lower extremity ulcers.
AB  - BACKGROUND: Diabetic foot ulcer is a major health care problem that leads to
      amputation. METHODS: Patients with full-thickness diabetic neurotrophic foot
      ulcers present for longer than 8 weeks without healing were entered into one of
      five randomized, prospective, blinded clinical trials comparing treatment with
      platelet-derived growth factor (PDGF) or placebo gel for up to 20 weeks. The
      purpose of these trials was to assess the safety and efficacy of PDGF used with
      good wound care. Each patient had an adequate arterial blood supply, was free of
      infection, was off-loaded, and was extensively debrided. The ulcers had been
      present for at least 8 weeks. RESULTS: A total of 922 patients were entered into
      the study. Analysis of ulcers with a baseline area of less than 10 cm (95 percent
      of patients) showed that patients treated with PDGF at 100 mug/g had a
      significant increase in complete healing compared with patients given placebo (50
      percent versus 36 percent, p < 0.007). PDGF also decreased the time to complete
      healing by 30 percent (14 weeks versus 20 weeks, p = 0.01). Adverse events were
      similar in both treatment groups, as were recurrent ulcer rates. CONCLUSION: PDGF
      applied once daily was effective in healing chronic diabetic neurotrophic foot
      ulcers when used in conjunction with good wound care.

PMID- 16799383
TI  - The efficacy of Apligraf in the treatment of diabetic foot ulcers.
AB  - Diabetic foot ulcerations can be a devastating complication of diabetes, causing
      prolonged hospitalization and significant morbidity. Previously identified risk
      factors include peripheral neuropathy, foot deformities, and poor wound healing
      due to an altered wound environment. Despite appropriate treatment, many diabetic
      ulcers fail to heal. Bioengineered tissue, such as Apligraf (Graftskin;
      Organogenesis Inc., Canton, Mass.), has been effectively and safely used to
      increase the incidence of complete wound closure and decrease the healing time.
      Studies have demonstrated that Apligraf works through the delivery of growth
      factors and cytokines to the chronic wound environment.

PMID- 16799385
TI  - Reconstructive surgery with Integra dermal regeneration template: histologic
      study, clinical evaluation, and current practice.
AB  - BACKGROUND: Yannas and Burke developed the concept of the dermal regeneration
      template in the 1970s. It is now a widely accepted tool in the treatment of burns
      as well as in reconstructive surgery. METHODS: The authors present a previously
      published study of Integra used in 20 consecutive patients to reconstruct 30
      anatomical sites and then analyze the histologic and clinical outcomes. Wound
      healing was evaluated by examination of weekly punch biopsy specimens with
      standard and immunohistochemical stains. Patient satisfaction was assessed using
      a visual analogue scale, and scar appearance was assessed using a modified
      Vancouver Scar Scale. RESULTS: Four distinct phases of dermal regeneration could
      be demonstrated histologically: imbibition, fibroblast migration,
      neovascularization, and remodeling and maturation. Full vascularization of the
      neodermis occurred at 4 weeks. Patients reported increased range of movement and
      improvement in appearance compared with their preoperative states. CONCLUSIONS:
      The color of the matrix reflected the stage of neodermal vascularization. No
      adnexa, nerve endings, or elastic fibers were seen in any of the specimens. The
      new collagen was histologically indistinguishable from normal dermal collagen.
      The authors also present their current protocol and experience with using Integra
      for a range of reconstructive procedures.

PMID- 16799386
TI  - An evidence-based appraisal of the use of hyperbaric oxygen on flaps and grafts.
AB  - Hyperbaric oxygen has been advocated, both as an adjunctive or primary form of
      treatment, for a variety of disorders, including gas gangrene,
      osteoradionecrosis, and carbon monoxide poisoning. It has also been used to
      improve ischemic wounds before skin grafting and to support ischemic flaps. In
      this review, we analyze the available literature that investigates the use of
      hyperbaric oxygen for composite grafts, skin grafts, random flaps, distant flaps,
      and free flaps. An appraisal of the level of evidence for each of these uses of
      hyperbaric oxygen is offered. Although there are a significant amount of animal
      data supporting the application of hyperbaric oxygen for grafts and flaps, there
      is very little clinical information other than case reports and series to sustain
      its choice over other modalities of therapy. Multicenter prospective clinical
      studies are clearly needed comparing hyperbaric oxygen to other mechanical or
      pharmacologic interventions to improve wound healing for grafting or to support
      flap survival.

PMID- 16799390
TI  - Diagnosis and treatment of diabetic foot infections.
AB  - EXECUTIVE SUMMARY: 1. Foot infections in patients with diabetes cause substantial
      morbidity and frequent visits to health care professionals and may lead to
      amputation of a lower extremity. 2. Diabetic foot infections require attention to
      local (foot) and systemic (metabolic) issues and coordinated management,
      preferably by a multidisciplinary foot-care team (A-II). The team managing these
      infections should include, or have ready access to, an infectious diseases
      specialist or a medical microbiologist (B-II). 3. The major predisposing factor
      to these infections is foot ulceration, which is usually related to peripheral
      neuropathy. Peripheral vascular disease and various immunological disturbances
      play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus
      aureus) are the predominant pathogens in diabetic foot infections. Patients who
      have chronic wounds or who have recently received antibiotic therapy may also be
      infected with Gram-negative rods, and those with foot ischemia or gangrene may
      have obligate anaerobic pathogens. 5. Wound infections must be diagnosed
      clinically on the basis of local (and occasionally systemic) signs and symptoms
      of inflammation. Laboratory (including microbiological) investigations are of
      limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6.
      Send appropriately obtained specimens for culture before starting empirical
      antibiotic therapy in all cases of infection, except perhaps those that are mild
      and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer
      curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging
      studies may help diagnose or better define deep, soft-tissue purulent collections
      and are usually needed to detect pathological findings in bone. Plain radiography
      may be adequate in many cases, but MRI (in preference to isotope scanning) is
      more sensitive and specific, especially for detection of soft-tissue lesions (A
      I). 8. Infections should be categorized by their severity on the basis of readily
      assessable clinical and laboratory features (B-II). Most important among these
      are the specific tissues involved, the adequacy of arterial perfusion, and the
      presence of systemic toxicity or metabolic instability. Categorization helps
      determine the degree of risk to the patient and the limb and, thus, the urgency
      and venue of management. 9. Available evidence does not support treating
      clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy
      is necessary for virtually all infected wounds, but it is often insufficient
      without appropriate wound care. 10. Select an empirical antibiotic regimen on the
      basis of the severity of the infection and the likely etiologic agent(s) (B-II).
      Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to
      moderate infections in patients who have not recently received antibiotic therapy
      (A-II). Broad-spectrum empirical therapy is not routinely required but is
      indicated for severe infections, pending culture results and antibiotic
      susceptibility data (B-III). Take into consideration any recent antibiotic
      therapy and local antibiotic susceptibility data, especially the prevalence of
      methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive
      therapy should be based on both the culture results and susceptibility data and
      the clinical response to the empirical regimen (C-III). 11. There is only limited
      evidence with which to make informed choices among the various topical, oral, and
      parenteral antibiotic agents. Virtually all severe and some moderate infections
      require parenteral therapy, at least initially (C-III). Highly bioavailable oral
      antibiotics can be used in most mild and in many moderate infections, including
      some cases of osteomyelitis (A-II). Topical therapy may be used for some mild
      superficial infections (B-I). 12. Continue antibiotic therapy until there is
      evidence that the infection has resolved but not necessarily until a wound has
      healed. Suggestions for the duration of antibiotic therapy are as follows: for
      mild infections, 12 weeks usually suffices, but some require an additional 12
      weeks; for moderate and severe infections, usually 24 weeks is sufficient,
      depending on the structures involved, the adequacy of debridement, the type of
      soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis,
      generally at least 46 weeks is required, but a shorter duration is sufficient if
      the entire infected bone is removed, and probably a longer duration is needed if
      infected bone remains (B-II). 13. If an infection in a clinically stable patient
      fails to respond to 1 antibiotic courses, consider discontinuing all
      antimicrobials and, after a few days, obtaining optimal culture specimens (C
      III). 14. Seek surgical consultation and, when needed, intervention for
      infections accompanied by a deep abscess, extensive bone or joint involvement,
      crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II).
      Evaluating the limb's arterial supply and revascularizing when indicated are
      particularly important. Surgeons with experience and interest in the field should
      be recruited by the foot-care team, if possible. 15. Providing optimal wound
      care, in addition to appropriate antibiotic treatment of the infection, is
      crucial for healing (A-I). This includes proper wound cleansing, debridement of
      any callus and necrotic tissue, and, especially, off-loading of pressure. There
      is insufficient evidence to recommend use of a specific wound dressing or any
      type of wound healing agents or products for infected foot wounds. 16. Patients
      with infected wounds require early and careful follow-up observation to ensure
      that the selected medical and surgical treatment regimens have been appropriate
      and effective (B-III). 17. Studies have not adequately defined the role of most
      adjunctive therapies for diabetic foot infections, but systematic reviews suggest
      that granulocyte colony-stimulating factors and systemic hyperbaric oxygen
      therapy may help prevent amputations (B-I). These treatments may be useful for
      severe infections or for those that have not adequately responded to therapy,
      despite correcting for all amenable local and systemic adverse factors. 18.
      Spread of infection to bone (osteitis or osteomyelitis) may be difficult to
      distinguish from noninfectious osteoarthropathy. Clinical examination and imaging
      tests may suffice, but bone biopsy is valuable for establishing the diagnosis of
      osteomyelitis, for defining the pathogenic organism(s), and for determining the
      antibiotic susceptibilities of such organisms (B-II). 19. Although this field has
      matured, further research is much needed. The committee especially recommends
      that adequately powered prospective studies be undertaken to elucidate and
      validate systems for classifying infection, diagnosing osteomyelitis, defining
      optimal antibiotic regimens in various situations, and clarifying the role of
      surgery in treating osteomyelitis (A-III).

PMID- 16799388
TI  - Evidence-based protocol for diabetic foot ulcers.
AB  - BACKGROUND: Diabetic foot ulcers are the single biggest risk factor for
      nontraumatic foot amputations in persons with diabetes. Foot ulcers occur in 12
      to 25 percent of persons with diabetes and precede 84 percent of all nontraumatic
      amputations in this growing population. Because of the high incidence of foot
      ulcers, amputations remain a source of morbidity and mortality in persons with
      diabetes. Strict adherence to evidence-based protocols as described herein will
      prevent the majority of these amputations. METHODS: The collective experience of
      treating patients with neuropathic diabetic foot ulcers in four major diabetic
      foot programs in the United States and Europe was analyzed. RESULTS: The
      following protocol was developed for patients with diabetic foot ulcers: (1)
      establishment of good communication among the patient, the wound healing team,
      and the primary medical doctor; (2) comprehensive, protocol-driven care of the
      entire patient, including hemoglobin A1c, microalbuminuria, and cholesterol as
      well as early treatment of retinopathy, nephropathy, and cardiac disease; (3)
      weekly objective measurement of the wound with digital photography, planimetry,
      and documentation of the wound-healing process using the Wound Electronic Medical
      Record, if available; (4) objective evaluation of blood flow in the lower
      extremities (e.g., noninvasive flow studies); (5) debridement of hyperkeratotic,
      infected, and nonviable tissue; (6) use of systemic antibiotics for deep
      infection, drainage, and cellulitis; (7) off-loading; (8) maintenance of a moist
      wound bed; (9) use of growth factor and/or cellular therapy if the wound is not
      healing after 3 weeks with this protocol; and (10) consideration of the use of
      vacuum-assisted therapy in complex wounds. CONCLUSIONS: In diabetic foot ulcers,
      availability of the above modalities, in combination with early recognition and
      comprehensive treatment, ensures rapid healing, minimizes morbidity and mortality
      rates, and eliminates toe and limb amputations in the absence of ischemia and
      osteomyelitis.

PMID- 16799392
TI  - Early change in wound area as a predictor of healing in diabetic foot ulcers:
      knowing "when to say when".

PMID- 16799391
TI  - Percent change in wound area of diabetic foot ulcers over a 4-week period is a
      robust predictor of complete healing in a 12-week prospective trial.
AB  - OBJECTIVE: To assess the ability of the 4-week healing rate to predict complete
      healing over a 12-week period in a large prospective multicenter trial of
      diabetic patients with foot ulceration. RESEARCH DESIGN AND METHODS: We examined
      the change in ulcer area over a 4-week period as a predictor of wound healing
      within 12 weeks in patients who were seen weekly in a prospective, randomized
      controlled trial. RESULTS: Wound area measurements at baseline and after 4 weeks
      were performed in 203 patients. The midpoint between the percentage area
      reduction from baseline at 4 weeks in patients healed versus those not healed at
      12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater
      than the 4-week median had a 12-week healing rate of 58%, whereas those with
      reduction in ulcer area less than the 4-week median had a healing rate of only 9%
      (P < 0.01). The absolute change in ulcer area at 4 weeks was significantly
      greater in healers versus nonhealers (1.5 versus 0.8 cm2, P < 0.02). The percent
      change in wound area at 4 weeks in those who healed was 82% (95% CI 70-94),
      whereas in those who failed to heal, the percent change in wound area was 25% (15
      35; P < 0.001). CONCLUSIONS: The percent change in foot ulcer area after 4 weeks
      of observation is a robust predictor of healing at 12 weeks. This simple tool may
      serve as a pivotal clinical decision point in the care of diabetic foot ulcers
      for early identification of patients who may not respond to standard care and may
      need additional treatment.

PMID- 16799393
TI  - The role of activity, adherence, and off-loading on the healing of diabetic foot
      wounds.
AB  - The etiology of diabetic foot ulcerations is commonly associated with the
      presence of peripheral neuropathy and repetitive trauma due to normal walking
      activities to areas of the foot exposed to moderate or high pressure. The goal of
      any treatment plan should include as a central tenet the mitigation or modulation
      of this activity and/or pressure. While numerous studies have detailed the
      potential pressure off-loading properties of various treatment modalities,
      subsequent studies have suggested that, if easily removable, these therapies will
      likely not be used for the majority of steps taken each day. This serves to
      explain at least in part the often disappointing results of both these pressure
      off-loading technologies and advanced wound-healing therapies. This article
      reviews these data and suggests that an amalgam of effective pressure relief
      coupled with strategies to reduce nonadherence to this therapy could yield a
      potentially favorable clinical result.

PMID- 16799394
TI  - Current management of venous ulceration.
AB  - It has been estimated that chronic venous insufficiency affects 10 to 35 percent
      of the entire U.S. population and that 4 percent of people older than 65 have
      active venous ulcers. The high prevalence of the disease results in an annual
      expenditure of more than 1 billion dollars a year to the U.S. health care system.
      To have a rational approach toward patients with venous ulcers, it is important
      to understand the pathophysiology and clinical characteristics of the disease
      process, in order to initiate appropriate treatment and prevent venous ulcer
      recurrence.

PMID- 16799395
TI  - Angiosomes of the foot and ankle and clinical implications for limb salvage:
      reconstruction, incisions, and revascularization.
AB  - BACKGROUND: Ian Taylor introduced the angiosome concept, separating the body into
      distinct three-dimensional blocks of tissue fed by source arteries. Understanding
      the angiosomes of the foot and ankle and the interaction among their source
      arteries is clinically useful in surgery of the foot and ankle, especially in the
      presence of peripheral vascular disease. METHODS: In 50 cadaver dissections of
      the lower extremity, arteries were injected with methyl methacrylate in different
      colors and dissected. Preoperatively, each reconstructive patient's vascular
      anatomy was routinely analyzed using a Doppler instrument and the results were
      evaluated. RESULTS: There are six angiosomes of the foot and ankle originating
      from the three main arteries and their branches to the foot and ankle. The three
      branches of the posterior tibial artery each supply distinct portions of the
      plantar foot. The two branches of the peroneal artery supply the anterolateral
      portion of the ankle and rear foot. The anterior tibial artery supplies the
      anterior ankle, and its continuation, the dorsalis pedis artery, supplies the
      dorsum of the foot. Blood flow to the foot and ankle is redundant, because the
      three major arteries feeding the foot have multiple arterial-arterial
      connections. By selectively performing a Doppler examination of these
      connections, it is possible to quickly map the existing vascular tree and the
      direction of flow. CONCLUSIONS: Detailed knowledge of the vascular anatomy of the
      foot and ankle allows the plastic surgeon to plan vascularly sound
      reconstructions, the foot and ankle surgeon to design safe exposures of the
      underlying skeleton, and the vascular surgeon to choose the most effective
      revascularization for a given wound.

PMID- 16799396
TI  - PKC-B inhibition: a new therapeutic approach for diabetic complications?
AB  - PKC comprises a superfamily of isoenzymes that is activated in response to
      various stimuli. Hyperglycaemia induces the activation of different PKC isoforms.
      However, the PKC-B isoform appears to be preferentially activated by high glucose
      levels and has been shown to be associated with diabetic vascular complications.
      In vitro and in vivo animal studies have shown that ruboxistaurin mesylate, a
      novel selective inhibitor of PKC-B ameliorates the biochemical and functional
      consequences of PKC activation and may have the potential to reduce the burden of
      vascular complications associated with diabetes. Results of the first phase-II
      and phase-III trials evaluating the efficacy of this compound on diabetic
      microvascular complications have been published recently. They confirm that this
      compound may favorably influence the evolution of diabetic microvascular
      complications.

PMID- 16799397
TI  - Prevalence of metabolic abnormalities in the Tunisian adults: a population based
      study.
AB  - AIMS: To estimate the prevalence of individual metabolic abnormalities and the
      cluster of metabolic abnormalities in a representative sample of the Tunisian
      adult population and to identify their relationship with gender, age and
      residency. The definition used is an adaptation of the NCEP ATP III definition,
      using total cholesterol>or=5.2 mmol/l instead of HDL-cholesterol. MATERIALS AND
      METHODS: We used a sample of the Tunisian National Nutrition Survey (TNNS), a
      cross-sectional health survey conducted in 1996, to estimate the nutritional
      status of the population. The TNNS included 2 927 adults aged 20 years or older
      who had measurements of height, body weight, waist circumference, blood pressure,
      fasting plasma glucose, total cholesterol and triglycerides. The cluster of
      metabolic abnormalities was defined as the presence of three or more metabolic
      abnormalities. RESULTS: The prevalence of abdominal obesity,
      hypertriglyceridemia, high total cholesterol, high blood pressure and high
      fasting plasma glucose was, respectively, 9%, 23%, 24%, 45% and 15% in men and
      33%, 19%, 29%, 44% and 15% in women. The prevalence of the cluster was more
      frequent in women than in men (18% versus 13%, P<0.001) and in those living in
      urban communities (21% in women, 16% in men) rather than rural communities (11%
      in women, 8% in men) (P<0.001). The prevalence also increased significantly with
      age (P<0.001). CONCLUSION: The cluster of metabolic abnormalities and its
      components are common in the Tunisian adult population and prevalence increases
      significantly with female sex, urban residency and age.

PMID- 16799398
TI  - C-peptide replacement improves weight gain and renal function in diabetic rats.
AB  - AIM: Recent experimental and clinical data suggest that C-peptide replacement
      during type 1 diabetes exerts beneficial effects on diabetic nephropathy. The aim
      of this study was to determine if physiological C-peptide administration in
      replacement dose during 28 days had beneficial effects on metabolic status and
      renal functions in type-1 diabetic rats. METHODS: Four groups of rats were
      investigated: a non diabetic group treated with buffer (C group, n=6), three
      streptozotocin diabetic-induced groups treated with either buffer (D group, n=6),
      insulin (D-I group, n=6) or rat homologous C-peptide (D-C group, n=6). Weight
      gain was measured every week. All animals were housed in metabolic cages on day
      28 for assessment of metabolic data. Blood and urine samples were collected to
      allow measurement of plasmatic osmolality, C-peptide concentration, sodium, and
      glucose losses and proteinuria. Glomerular filtration rate (GFR) was determined
      by creatinine clearance. RESULTS: All streptozotocin-treated animals were
      diabetic. Glycaemic control (mg/dl), was markedly improved in D-I (133+/-65) when
      compared with either D (547+/-49, P<0.05) or D-C (520+/-48, P<0.05) groups.
      Conversely, weight gain during the study, was improved in D-I and D-C as compared
      with D animals (135+/-13 and 41+/-18 vs 18+/-21 respectively), despite different
      glycaemic control. Diabetes-induced glomerular hyperfiltration (ml/min/kg),
      urinary protein leakage (g/kg/day), and Na urinary losses (mmol/100 g/day)
      respectively, were significantly (P<0.05) reduced in D-C (3.95+/-0.6; 0.08+/
      0.06; 1.5+/-0.9) in comparison with D (4.95+/-0.8; 0.18+/-0.16; 3.7+/-2.1) and D
      I (5+/-0.9; 0.19+/-0.11; 2.7+/-0.8) animals. Plasmatic osmolality was
      significantly increased in D group whereas there were no differences between C
      group and D-C group. Food and water intakes, urinary volume as well as urinary
      glucose losses were not significantly different between D-C and D groups.
      CONCLUSIONS: C-peptide administration in replacement dose to streptozotocin
      diabetic rats induces weight gain regardless hyperglycaemia or glycosuria.
      Diabetic animals supplemented with C-peptide exhibit better renal function
      resulting in reduced urinary sodium waste and protein excretion together with
      reduction of the diabetes-induced glomerular hyperfiltration.

PMID- 16799399
TI  - Differential effects of peroxisome proliferator-activated receptor ligands and
      sulfonylurea plus statin treatment on plasma concentrations of adipokines in type
      2 diabetes with dyslipidemia.
AB  - OBJECTIVES: Peroxisome proliferator-activated receptor gamma is the master
      regulator of adipocyte differentiation and controls many adipocyte genes in
      response to anti-diabetic thiazolidinediones (TZDs) and lipid-lowering fibrates.
      We hypothesized that the combination of TZD+fibrate may be better than the
      sulfonylurea + statin approach regarding modifying the adipokine profile in
      diabetic patients with dyslipidemia. METHODS: We measured the lipid profiles and
      circulating levels of adiponectin, resistin, and inflammatory markers before and
      after treatment in 24 type 2 diabetic patients with dyslipidemia (aged 64+/-9
      years; M/F=5/19). The study patients were randomly assigned to receive an 8-week
      treatment of either rosiglitazone 4 mg daily and fenofibrate 160 mg daily (PPAR
      group) or glibenclamide 5 mg daily and atorvastatin 10 mg daily (non-PPAR group).
      RESULTS: Even though the administration of sulfonylurea+statin can achieve a
      greater reduction of total cholesterol and LDL-cholesterol levels and a
      comparable glucose control compared to PPAR treatment, their administration did
      not change the plasma adipokine levels significantly. In contrast, a significant
      greater increase of the plasma concentrations of adiponectin (P<0.0001), a trend
      to a greater decrease of the plasma resistin levels (P=0.061), a significantly
      greater increase of HDL-cholesterol (P=0.002), and a significantly greater
      reduction of triglyceride levels (P=0.018) were seen in the PPAR group.
      CONCLUSIONS: Considering the clinical significance of the adipokine-endothelial
      interaction in the progression and long-term prognosis of atherosclerosis, the
      differential effects of PPAR ligands and sulfonylurea+statin on plasma adipokine
      concentrations demonstrated in this study are interesting foci of investigation
      in the future.

PMID- 16799400
TI  - Insulinemia and leptinemia in geriatric patients: markers of the metabolic
      syndrome or of undernutrition?
AB  - The metabolic syndrome (MS) describes a cluster of metabolic disturbances
      including type 2 diabetes and/or insulin resistance, hypertension, dyslipidemia
      and obesity, which predict a high risk of cardiovascular disorders. The
      associated hyperinsulinemia and hyperleptinemia may contribute to the
      cardiovascular risk. However, the operational value of the MS in elderly patients
      is questionable. We therefore investigated the prevalence and significance of the
      MS in geriatric care. In a survey of 98 consecutive admissions of diabetic
      patients, <40% had a MS; this is a low value compared to younger diabetic adults,
      due to a low prevalence of obesity and dyslipidemia. We found a high prevalence
      of low BMI (<20 kg/m2), hypoalbuminemia and low total cholesterol levels,
      suggesting that the MS may be modified by undernutrition. The interplay between
      the MS and undernutrition was further studied in 30 non-diabetic patients. Both
      leptinemia and insulin resistance indexes (HOMA-IR and QUICKI) were strongly
      associated with BMI and body fat (measured by Bioelectrical impedance Analysis).
      BMI, leptinemia and insulin resistance indexes were associated with the Mini
      Nutritional Assessment (MNA) score. Thus, undernutrition is associated with low
      leptin and insulin levels and may obscure the association of these parameters
      with cardiovascular risk. In conclusion, the MS has a low prevalence in our
      population of elderly diabetic patients, and is of questionable prognostic value.
      It can be oveshadowed by undernutrition, which is associated with low body
      weight, leptinemia and insulin resistance indexes. Prevention of undernutrition
      and/or adjustment to its consequences should receive higher priority in the care
      of elderly diabetic patients.

PMID- 16799401
TI  - Insulin initiation in type 2 diabetic patients admitted in hospital in France and
      follow-up at 1 year.
AB  - OBJECTIVES AND METHODS: The IDAHO 2 epidemiological survey was conducted in
      departments of diabetology in insulin-naive type 2 diabetics for whom insulin was
      initiated. The objective was to assess the patients' profile, the treatments
      proposed during hospital stay and after one year. RESULTS: 797 patients were
      analysed. Their characteristics were: age 64+/-12 years, 49% males, weight: 78+/
      17 kg, BMI: 29+/-6 kg/m2, diabetes duration 11 years, prevalence of
      complications: 68%, fasting blood glucose 13+/-6 mmol/l, HbA1c: 10+/-2.2%;
      treatment prior to insulin comprised: at least 2 OHA: 71% of cases, one: 21%, no
      OAD: 8%. At hospital discharge, 54% of the patients used basal insulin. After 1
      year, 670 continued on insulin. The insulin initiation was accompanied by a
      decrease in the FBG level (baseline: 13+/-6 mmol/l; final: 8.5+/-2.75 mmol/l;
      P<0.0001) and a HbA1c improvement (baseline: 10+/-2.2%; final: 7.9+/-1.4%;
      P<0.0001). This was observed du-ring the first 6 months (HbA1c: 7.8%, P<0.0001
      versus baseline). 80% of the patients remained on the same insulin regimen after
      1 year: 35% had 1 injection/day, 44% had 2, 12% had 3 and 9% had a complex
      regimen. The weight gain, the final daily dose and hypoglycaemias increased with
      the number of injections. The mean daily insulin dose was 33 U/day (24 U with 1
      injection/day). CONCLUSION: The IDAHO study shows that insulin is effective in
      type 2 diabetics however, management is inadequate with insulin therapy being
      initiated too late and at doses which are low after one year.

PMID- 16799402
TI  - Surrogate indexes vs. euglycaemic-hyperinsulinemic clamp as an indicator of
      insulin resistance and cardiovascular risk factors in overweight and obese
      postmenopausal women.
AB  - BACKGROUND: There is considerable interest in validating the most convenient
      method to estimate insulin sensitivity in clinical research protocols that could
      best indicate cardiovascular risk factors. To address this issue we examined the
      interrelationships of several cardiovascular risk factors with surrogate indexes
      such as fasting insulin, the homeostasis model assessment (HOMA), the
      quantitative insulin sensitivity check index (QUICKI) and the revised QUICKI vs
      the euglycaemic-hyperinsulinemic (EH) clamp in a non-diabetic overweight or obese
      postmenopausal female population. DESIGN: Cross-sectional study involving 88
      obese postmenopausal women (age: 57.5+/-5.0 yrs; body mass index: 32.52+/-4.4
      kg/m2; percent body fat: 46.35+/-4.9%). METHODS: Insulin sensitivity was
      determined by the EH clamp technique as well as by surrogate indexes such as
      fasting insulin, HOMA, log HOMA, QUICKI and revised QUICKI. Body composition and
      body fat distribution were measured using dual energy x-ray absorptiometry and
      computed tomography, respectively. RESULTS: Correlations between insulin
      resistance indexes (fasting insulin, revised QUICKI, QUICKI, log HOMA, HOMA) vs
      glucose disposal were similar (range of r's=0.40 to 0.49), suggesting that no
      index was superior to another with respect to its relationship with the EH clamp.
      Correlations between the insulin resistance indexes with plasma lipids were
      comparable among all indexes, however, systolic blood pressure, visceral fat and
      C-reactive protein were moderately superior with index vs the EH clamp.
      CONCLUSION: Surrogate measures of insulin resistance, in particular fasting
      insulin, are simple tools appropriate for epidemiological studies that can be
      used as substitutes for the EH clamp to estimate glucose disposal and
      cardiovascular risk factors in overweight and obese postmenopausal women.

PMID- 16799403
TI  - Educating diabetic patients about insulin use: changes over time in certainty and
      correctness of knowledge.
AB  - AIM: Diabetic patients should understand their disease correctly and be sure of
      what they know, but certainty is rarely considered by educators. Furthermore
      little is known about how certainty changes with time after an educational
      intervention. To clarify this, in 38 patients with type 1 diabetes (0.3-36 years
      duration) we analysed the effect of a course on insulin use by administering a
      questionnaire before the course, after the course and 1 and 3 years later.
      METHODS: Answers, accompanied by a subjective estimate of the degree of
      certainty, were assigned to mastered knowledge (certainty>or=90%,
      correctness>or=90%), hazardous knowledge (certainty>or=90%, correctness<or=50%),
      uncertain knowledge (certainty<or=50%, correctness>or=90%) and residual knowledge
      (total-[mastered+hazardous+uncertain]). Answers were then counted and changes in
      distribution among areas were analysed by the chi2 test. We also followed the
      fate of wrong answers. RESULTS: The course increased mastered knowledge, while
      other types of knowledge decreased. With time mastered knowledge decreased,
      patients losing both correctness and certainty. The loss affected declarative
      knowledge, based purely on theory, more than procedural knowledge, which concerns
      the way things are done. Wrong answers, mostly given with high degree of
      certainty, were heterogeneous since some became correct after the course, some
      remained wrong, some became wrong after the course, some became mistaken after
      having been corrected earlier. CONCLUSIONS: The analysis of certainty helps in
      evaluating patient's knowledge; programmes tending to improve procedural
      knowledge are more likely to have long lasting effects; wrong answers need to be
      considered on a individual basis.

PMID- 16799404
TI  - . Association of HindIII and PvuII genetic polymorphisms of lipoprotein lipase
      with lipid metabolism and macrovascular events in type 2 diabetic patients.
AB  - AIM: Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism, and its
      genetic polymorphism may be a candidate for modulating lipid parameters in type 2
      diabetic subjects (D2). METHODS: In a group of 404 type 2 diabetic patients, aged
      59.5+/-10.8y, BMI=28.9+/-5.3 kg/m2, HbA1c=8.2+/-1.9%, we studied the H and P
      polymorphisms at the LPL locus detectable with the restriction enzymes HindIII
      and PvuII. Patients were separated into 229 males (17H1H1, 84H1H2, 128H2H2 and
      51P1P1, 110P1P2, 68P2P2) and 175 females (16H1H1, 69H1H2, 90H2H2 and 51P1P1,
      85P1P2, 39P2P2), and compared on the basis of their lipid parameters and their
      macrovascular complications. RESULTS: Triglyceride (TG) and HDL-cholesterol(c)
      concentrations differed between patients with and without coronary heart disease
      (CHD) (3.44+/-2.09 and 1.96+/-1.40 mmol/l for TGs and 1.05+/-0.24 and 1.34+/-0.40
      mmol/l for HDL-c, P<0.001). HDL-c concentrations were lower in male H2H2 and P2P2
      subjects (P<0.001), and TG levels were higher in male H2H2 and P2P2 subjects
      (P<0.0001 for Hind III and P<0.05 for PvuII). Allele frequency of the HindIII and
      PvuII restriction site was similar to those reported in other Caucasian
      populations and the presence of the H2/P2 variants was significantly higher in
      CHD patients. The prevalence of CHD in this population was 18% but was 29% in
      H2H2 and 38% in P2P2 subjects (P<0.02). CONCLUSION: Thus, HindIII and PvuII
      polymorphisms seem to exert a modulating role on lipid profile particularly in
      male D2, contributing to increase the risk of macrovascular events.

PMID- 16799405
TI  - Apolipoprotein E genotype and plasma lipid levels in Caucasian diabetic patients.
AB  - OBJECTIVE: Apo E polymorphism has been shown to affect lipid profiles in non
      diabetic and diabetic populations. We evaluated the relationship between Apo E
      phenotype and fasting lipid plasma levels in type 2 diabetes patients. METHODS:
      Two hundred and ten French type 2 diabetic patients (115 men and 95 women)
      without any lipid lowering drugs were studied. Fasting lipids were measured by
      usual methods and Apo E genotype was established for each patient: PCR was
      followed by digestion of the amplification product with restriction enzymes and
      separation of the fragments by polyacrylamide gel. RESULTS: Genotypes
      epsilon3/epsilon3, epsilon2/epsilon3 and epsilon3/epsilon4, epsilon2/epsilon2 and
      epsilon2/epsilon4 were found in 68.1%, 14.8%, 15.7%, 1.0% and 0.5%, respectively.
      No patient had the epsilon4/epsilon4 genotype. Lipid plasma levels were compared
      between E3 group (epsilon3/epsilon3) as a reference and E2 (epsilon2/epsilon2 or
      epsilon2/epsilon3) or E4 (epsilon3/epsilon4 or epsilon2/epsilon4). Total
      cholesterol, LDL cholesterol and Apo B levels were lower in the E2 group. Total
      cholesterol, LDL cholesterol and Apo B levels were higher in the E4 group. HDL
      cholesterol levels were increased in the E4 group, as only previously observed in
      Japanese populations. CONCLUSION: These results agree with those already reported
      in diabetic patients of several western European countries. E4 allele carriers
      have a greater cardio-vascular risk and this could be partially explained by the
      metabolic variation in lipid metabolism induced by E4 with higher LDL cholesterol
      and Apo B levels. These results observed in French diabetic subjects without any
      lipid-lowering drugs may be used as a reference for other studies performed in
      France.

PMID- 16799406
TI  - Insulin-dependent diabetes mellitus as long term complication of haemolytic
      uraemic syndrome.
AB  - Haemolytic-uraemic syndrome (HUS) is a rare cause of insulin-dependent diabetes
      mellitus during the acute stage. We previously reported the case of a 3-year-old
      girl having presented with typical HUS with diarrhea, microangiopathic anaemia,
      thrombocytopenia and acute renal failure (17 days of anuria). Transient
      hyperglycaemia (highest level: 513 mg/dl) was observed, requiring continuous
      intravenous insulin infusion for 9 days. Subcutaneous insulin injections were
      stopped after 24 days. Oral glucose tolerance test performed 4 months after
      normalization of blood glucose was normal. HLA DQ genotype (DQA1-DQB1.AZH/DQA3
      DQB3.1) was not at risk for type 1 diabetes and there were no auto-antibodies
      (ICA and IAA). The 3-years follow-up was marked by persistent arterial
      hypertension, proteinuria and slight renal insufficiency despite angiotensin
      converting enzyme inhibitor treatment. Ten years after HUS occurred (the patient
      had been lost to follow-up for 7 years), she came back with complaints of
      headache but neither polyurodipsia nor weight loss. She was found to have
      arterial hypertension. Chronic renal impairment had moderately progressed with
      decreased glomerular filtration rate (63 ml/min/1.73 m2) and proteinuria (2 g/24
      hours). Fasting blood glucose was 189 mg/dl and reached 315 mg/dl during an oral
      glucose tolerance test. HbA1c level was 8.2% (N<6.2%) and diabetes mellitus was
      diagnosed without any signs of autoimmunity (IAA, ICA, GADA and IA2B were
      negative). Good glycaemic control was obtained with 0.5 U/kg/day of insulin. In
      conclusion, transient beta-cell dysfunction complicating HUS acute stage may
      evolve to overt non-autoimmune diabetes mellitus (microangiopathic process?),
      even after a long free interval. This case emphasizes the need for a long-term
      follow-up of patients with HUS.

PMID- 16799408
TI  - Notice of retraction.

PMID- 16799407
TI  - Technical risks with subcutaneous insulin infusion.
AB  - The popularity of continuous subcutaneous insulin infusion (CSII), as a way for
      achieving long term strict glycaemic control in diabetic patients, has increased
      over the last ten years. Most reports on technical faults, often leading to
      metabolic emergencies, mainly ketoacidosis, have been published in the 1980s.
      Obstruction of infusion set and infection of infusion site are the most frequent
      events. Insulin precipitation or aggregation is thought to be one of the
      precipitating factors. Few data are available about failures of the pump itself.
      We report our experience of pump malfunctions recorded between 2001 and 2004 in
      376 pumps used by patients treated with CSII therapy in Brittany. Recent studies
      indicate a decrease of metabolic complication frequency during CSII. This
      suggests technical improvements and/or a greater experience of physicians in
      selecting and educating patients. We report instructions for monitoring insulin
      pump therapy that should be included in a formal educational program for pump
      users. Clinical studies using newly available devices should reassess technical
      risks associated with CSII.

PMID- 16799409
TI  - [Effects of transmission counts on image quality during simultaneous
      emission/transmission scan].
AB  - We compared the pre-injection transmission scan with the simultaneous
      emission/transmission scan (SET) using a body phantom in positron emission
      tomography (PET) to study the factors affecting emission (EMIS) images with
      different transmission (TRAN) data. The results showed that total count, region,
      scan method, and EMIS component influenced the bias and noise statistics. This
      influence was further passed on to the EMIS data and affected the reconstructed
      image. However, the result of fixing EMIS scan time at 10 minutes was that the
      noise statistics of EMIS had a greater effect on image quality than TRAN. The
      optimal scan counts of SET in this study were 20 Mcounts, with a scan time of
      about 10 minutes (85.5 MBq, (68)Ge-(68)Ga radioactivity). In clinical use,
      optimal collection count differs, as radiation TRAN quantity depends on the size
      of the subject, even with fixed radioactivity of (68)Ge-(68)Ga.

PMID- 16799411
TI  - [Comparison of activity expression between PET using 68Ge-68Ga line source
      attenuation correction and PET-CT using CT attenuation correction: impact on
      emission images].
AB  - OBJECTIVES: CT data can be used for both anatomical image and attenuation
      correction (CTAC) of PET data in PET-CT scanners. The CTAC method is useful for
      attenuation correction, because the CT scan time is much shorter than the
      external radionuclide (e.g., (68)Ge) transmission scan time. However, the energy
      of the X-rays from CT is not monoenergetic and is much lower than that of the
      external radionuclide source. In this study, we evaluated the differences between
      emission PET images reconstructed with CT-based and (68)Ge-based attenuation
      correction. METHODS: CT scans and (68)Ge-Transmission scans were acquired and
      used for attenuation correction (CTAC, MAC, and SAC). The PET emission scan time
      was 4 min. CT scans were acquired at 10, 20, 40, 80, and 160 mA. (68)Ge
      Transmission scans were acquired at 1, 3, 5, 10, 20, 40, 60, and 300 min. The
      attenuation-corrected emission image using MAC on a 300 min transmission scan was
      defined as the reference image. Seven cylinders (30 mm diameter) were filled with
      (18)F-FDG placed in a heart-liver phantom with simulated pulmonary mass lesions.
      The PET value [counts/cc] was measured in circular regions of interest (ROI) over
      the cylindrical mass lesion. Averages [counts/cc], coefficients of variation
      [C.V.(%)], and ratios of difference [%Diff] from the reference value were
      calculated for all conditions. RESULTS: In the CT-Transmission, analysis of
      variance revealed no significant effect of CT current on the average and the C.V.
      In the (68)Ge-Transmission, the average and the C.V. changed in dependence on the
      acquisition time. All %Diff using CT-Transmission were small. It was shown that
      CT-Transmission is more appropriate than (68)Ge-Transmission.

PMID- 16799410
TI  - [Assessment of whole body PET/MRI fusion imaging using automated software:
      usefulness of partial body fusion].
AB  - PURPOSE: In this study, we created a whole body fusion image of PET and MRI using
      automated software for fusion imaging, and assessed the accuracy of the software.
      MATERIALS AND METHODS: Twenty patients with abnormal FDG-PET findings underwent
      whole body MRI. Images from both modalities were automatically fused in two ways
      using software (Fusion Viewer, Nihon Medi-Physics Co., Ltd., Nishinomiya, Japan)
      with a registration algorithm based on maximum mutual information. One was to
      create a whole body fusion image at once, named whole body fusion (WBF). The
      other was to create fusion images of the head and body separately, named partial
      body fusion (PBF). Two radiologists measured the misregistration between PET and
      MRI in the fusion images at nine landmarks (brain, cervical spine, chest, heart,
      liver, right kidney, left kidney, vertebra, base of bladder). RESULTS: When
      fusion images were created using WBF at once, misregistration was observed in the
      head and neck area in approximately half of the cases, whereas almost no
      misregistration was observed in the body. When fusion images were created using
      PBF, the misregistration in the head and neck areas was significantly smaller
      than in those using WBF, and misregistration in the body was very small.
      CONCLUSION: The PBF technique that creates highly accurate whole body PET/MRI
      fusion images is easy to use and may provide clinically useful information.

PMID- 16799412
TI  - [Examination of attenuation correction using low-dose computed tomography].
AB  - Attenuation correction is necessary for the reconstruction of SPECT images. One
      report has mentioned that attenuation correction by X-ray computed tomography
      (CT) is effective for a non-uniform attenuation body. We examined the effect of
      attenuation correction on SPECT images by changing the scanning conditions of CT,
      and evaluated the possibility of attenuation correction by low-dose CT. The
      phantom was scanned under several X-ray tube conditions varying from 80 kV to 135
      kV and from 7.5 mAs to 200 mAs. We obtained equations of attenuation correction
      based on the Hounsfield Unit (HU) units of each pixel and compared the effects of
      attenuation correction. The results showed that the equation for attenuation
      correction under each condition did not vary significantly, and the effects of
      attenuation correction by the equations did not vary significantly between CT of
      low dose and that of clinical dose. This result suggest that the attenuation
      correction obtained by low-dose CT was equal to that obtained by the clinical
      dose. In conclusion, it seemed that the equation and map of attenuation
      correction matched with each radionuclide yielded more adequate attenuation
      correction than conventional methods.

PMID- 16799413
TI  - [Development of a new method of high-speed rotation multiplied projection single
      photon emission computed tomography of the triple-headed type: lung MAA SPECT
      based on phantom study].
AB  - PURPOSE: A chest phantom study was conducted to evaluate the image quality of
      newly developed high-speed rotation multiplied projection-single photon emission
      computed tomography (HSRMP-SPECT) images. MATERIALS AND METHODS: HSRMP-SPECT
      images of a chest phantom consisting of a simulated lung structure filled with
      5000 ml of water containing 185 MBq Tc-99m-pertechnetate, and several small 11 mm
      simulated lung nodules of glass balls and one large 35 mm simulated lung nodule
      of a plastic sphere filled with water were obtained using a triple-headed SPECT
      system. During image acquisition, this phantom was regularly moving in the head
      to-caudal direction with a range of 12 mm at a frequency of 15 cycles/min to
      simulate respiratory motion, and 360 degrees projection data of this moving
      phantom was acquired with an image acquisition time of 20 sec, which was repeated
      10 times. To eliminate the setting time between projection and acquisition of
      multiple temporal samples of data, each detector was continuously rotated in the
      clockwise direction for 20 sec around a 120-degree arc. On the perspective SPECT
      images reconstructed from various numbers of the 20-sec projection data, the
      perfusion heterogeneity of the simulated lungs and perfusion defect clarity of
      the simulated nodules were assessed by the coefficient of variation (CV) of pixel
      counts and the defect-to-lung radioactivity ratios, respectively. The results
      were compared with those on conventional SPECT images of the moving phantom
      obtained with a data acquisition time of 8 min, and SPECT images of the standing
      phantom obtained with the same data acquisition time. RESULTS: The average CV
      value of 0.28+/-0.01 on the SPECT image reconstructed from 5 projection data sets
      was not significantly different from that of 0.27+/-0.01 on the SPECT image
      reconstructed from 10 projection data sets (p<0.05). The perfusion defect
      contrast of the simulated nodules obtained from 5 projection data was
      significantly higher than that on conventional SPECT images (0.50 vs. 0.73) .
      CONCLUSIONS: The present phantom study indicated that HSRMP-SPECT could be a
      useful technique for quickly obtaining high-quality SPECT images of a moving
      subject, thereby improving perfusion defect clarity in comparison with the
      conventional technique. This technique may have potential utility for obtaining
      high-quality breath-hold SPECT images of the chest in clinical practice.

PMID- 16799414
TI  - [Examination of bed overlaps in 18F-FDG PET/CT 3D data acquisition].
AB  - The purpose of this study was to determine the best bed overlaps in PET/CT 3D
      acquisition to reconstruct a transverse image with uniform quality not depending
      on axial slice position. First, the value of the image contrast ratio, non
      uniformity (NU) value, and coefficient of variation (COV) were examined in the
      image of a cylindrical phantom at each slice position. The image-contrast ratio
      was almost constant in all slice images, and the NU value and COV were also
      constant in the slice images up to 13 and 19 slices from the center,
      respectively, but these values increased with closeness to the edge of the
      detector. Secondly, COV and image contrast ratios at different sizes of (18)F-FDG
      concentration (phi 19 mm, phi 16 mm, phi 13 mm, phi 10 mm) were examined in the
      case of overlapping the bed frame with 11, 15, and 21 slices in acquiring data in
      3D mode. In 21 and 15 slices overlapping in acquisition, the image contrast
      ratios for all concentrations were greater than 0.13, which was the threshold
      image contrast ratio needed to identify FDG concentration from the background
      image with naked eye scanning under our conditions. However, in 11 slices with
      overlapping acquisition, the image-contrast ratio for a phi 10 mm concentration
      were close to or less than 0.13 in the all slice images. As a result, 15
      overlapping slices was a reasonable minimum number of slices to identify a phi 10
      mm (18)F-FDG concentration while maintaining the image quality in PET/CT 3D
      acquisition in our institution.

PMID- 16799415
TI  - [Improvement of metal artifacts in dental structures by X-ray CT: reconstruction
      of transverse images using oblique images by gantry tilt scanning].

PMID- 16799416
TI  - Asking the right questions.

PMID- 16799417
TI  - Unproven case.

PMID- 16799418
TI  - Flawed methodology.

PMID- 16799419
TI  - Poor science.

PMID- 16799420
TI  - Is it me?

PMID- 16799421
TI  - Pandemic flu.

PMID- 16799422
TI  - Commitment to accessibility.

PMID- 16799436
TI  - Rationale for dental implants.
AB  - The clinical replacement of lost natural teeth by osseointegrated implants has
      represented one of the most significant advances in restorative dentistry. Two
      decades ago, a majority of dentists were sceptical about implants and rejected
      them entirely. Today it is rare to find a practitioner who does not work with
      dental implants or who is not actively participating in one of the many seminars
      or courses offered by universities, professional societies and implant
      manufacturers.

PMID- 16799437
TI  - Gardner's syndrome: a case report.
AB  - Gardner's syndrome is characterised by polyposis coli associated with multiple
      hard and soft tissue tumours including osteoma and odontoma. The major
      significance of the condition lies in the gastrointestinal polyposis which
      usually undergoes malignant change by the fourth decade. Extra-intestinal
      components may be apparent before those in the bowel, and their early detection
      may lead to appropriate evaluation and life saving treatment. A case is reported
      to demonstrate how important it is for general dental practitioners to be aware
      of the clinical and radiological characteristics of Gardner's syndrome.

PMID- 16799445
TI  - General health promotion in general dental practice--the involvement of the
      dental team. Part 1: a review of the evidence of effectiveness of brief public
      health interventions.
AB  - OBJECTIVES: To review the evidence of the effectiveness of dentists, dental teams
      and other healthcare workers in seven different brief public health interventions
      that might contribute to Government targets in cancer and circulatory disease.
      The interventions were: smoking prevention, smoking cessation, advice on alcohol
      consumption, diet counselling, advice on physical exercise, advice on skin cancer
      prevention and blood pressure monitoring. METHOD: A series of literature reviews,
      using a generic systematic approach, were undertaken to investigate the
      effectiveness of dentists, dental teams and other healthcare workers in each
      intervention. RESULTS: Apart from smoking cessation and dietary advice, no
      studies were identified on the effectiveness of dentists or dental teams in the
      interventions investigated. There is some evidence that dentists and dental teams
      can be effective in smoking cessation. There is minimal evidence for
      effectiveness in dietary counselling, and that which exists shows only a
      transient effect. There is evidence that other healthcare workers can have some
      effect in all interventions, though the effect in preventing skin cancer is
      questionable. CONCLUSIONS: Due to the paucity of studies undertaken, there is
      minimal evidence of effectiveness of dentists and dental teams in any of the
      seven interventions. However other healthcare workers are effective in most of
      them. Dentists and dental teams' involvement in such brief general health
      promotion interventions might contribute to Government targets on cancer and
      circulatory disease.

PMID- 16799446
TI  - The effectiveness of school dental screening: dental attendance and treatment of
      those screened positive.
AB  - OBJECTIVE: To determine dental attendance and treatment outcomes following two
      models of dental screening. DESIGN: An observational prospective cohort study.
      SETTING: Infant, primary and junior schools in the North West of England.
      SUBJECTS: Children aged six to nine years at the start of the study.
      INTERVENTIONS: Subjects received a screening examination according to either a
      'Traditional model' or 'New model' of school dental screening. MAIN OUTCOME
      MEASURES: Attendance at a dentist within four months of the intervention and
      treatment received by children referred via the 'New model' with caries in their
      permanent teeth. RESULTS: In the 'New model' of school dental screening 46% of
      screened positive and 41% of screened negative children attended a dentist during
      the study period. Some 44% of children referred with caries in permanent teeth
      attended a dentist and 53% of those attending received treatment for the referred
      condition. Larger proportions of children from disadvantaged backgrounds were
      screened positive but higher proportions of children from more affluent
      backgrounds attended the dentist and subsequently received treatment. CONCLUSION:
      School dental screening has a minimal impact on dental attendance and only a
      small proportion of screened positive children receive appropriate treatment. The
      programme fails to reduce inequalities in utilisation of dental services.

PMID- 16799447
TI  - General dental practitioners' perceptions of the West of Scotland Cancer
      Awareness Programme oral cancer campaign.
AB  - OBJECTIVES: The 2003/04 West of Scotland Cancer Awareness Programme (WoSCAP) oral
      cancer campaign was designed to raise public awareness of the signs and symptoms
      of oral cancer. The objectives of this study were to explore general dental
      practitioners' (GDPs) awareness and perceptions of the campaign, and its impact
      on local dental practices. METHODS: A self-completing questionnaire was sent to
      GDPs in the West of Scotland (N = 983) at the conclusion of the public awareness
      campaign. RESULTS: A response rate of 68.6% was achieved. Most dentists (92%) had
      heard of the campaign and a large percentage had displayed the promotional
      materials in their practice. The majority of respondents rated the campaign
      materials, including a television advertisement, in a very positive manner. Over
      40% of dentists reported that, during the active phase of the campaign, patients
      had asked for information concerning the programme, and 66% indicated that
      registered patients had asked for advice regarding a specific lesion.
      Additionally, 41% of dentists reported non-registered patients had attended
      asking for advice regarding a 'worrying' lesion. Over 60% of dentists had
      referred a patient during the campaign and 40% of these practitioners indicated
      an increased referral rate during this period. CONCLUSIONS: Most respondents were
      positive in their assessment of the campaign and reported an increased awareness
      of oral cancer among patients.

PMID- 16799460
TI  - Sema4D/plexin-B1 activates GSK-3beta through R-Ras GAP activity, inducing growth
      cone collapse.
AB  - Plexins are receptors for the axonal guidance molecules known as semaphorins, and
      the semaphorin 4D (Sema4D) receptor plexin-B1 induces repulsive responses by
      functioning as an R-Ras GTPase-activating protein (GAP). Here we characterized
      the downstream signalling of plexin-B1-mediated R-Ras GAP activity, inducing
      growth cone collapse. Sema4D suppressed R-Ras activity in hippocampal neurons, in
      parallel with dephosphorylation of Akt and activation of glycogen synthase kinase
      (GSK)-3beta. Ectopic expression of the constitutively active mutant of Akt or
      treatment with GSK-3 inhibitors suppressed the Sema4D-induced growth cone
      collapse. Constitutive activation of phosphatidylinositol-3-OH kinase (PI(3)K),
      an upstream kinase of Akt and GSK-3beta, also blocked the growth cone collapse.
      The R-Ras GAP activity was necessary for plexin-B1-induced dephosphorylation of
      Akt and activation of GSK-3beta and was also required for phosphorylation of a
      downstream kinase of GSK-3beta, collapsin response mediator protein-2. Plexin-A1
      also induced dephosphorylation of Akt and GSK-3beta through its R-Ras GAP
      activity. We conclude that plexin-B1 inactivates PI(3)K and dephosphorylates Akt
      and GSK-3beta through R-Ras GAP activity, inducing growth cone collapse.

PMID- 16799461
TI  - Broadening of DNA replication origin usage during metazoan cell differentiation.
AB  - We have examined whether replication of the chicken beta-globin locus changes
      during differentiation of primary erythroid progenitors into erythrocytes. In
      undifferentiated progenitors, four principal initiation sites and a replication
      fork pausing region (RFP) were observed. Forty-eight hours after induction of
      differentiation, the principal sites were maintained, even in the activated
      beta(A)-globin gene, some minor sites were enhanced, three new sites appeared and
      the RFP disappeared. One of the activated origins showed increased histone H3
      K9K14 diacetylation, but the others did not. These results demonstrate a
      broadening of DNA replication origin usage during differentiation of
      untransformed metazoan cells and indicate that histone H3 diacetylation, other
      histone modifications so far reported and transcription are not crucial
      determinants of origin selection in this system.

PMID- 16799462
TI  - Hyped-up for Hox in Hyderabad. Workshop on upstream and downstream of Hox genes.

PMID- 16799463
TI  - Low oxygen stimulates the intellect. Symposium on hypoxia and development,
      physiology and disease.

PMID- 16799464
TI  - Rapid peptide bond formation on isolated 50S ribosomal subunits.
AB  - The catalytic site of the ribosome, the peptidyl transferase centre, is located
      on the large (50S in bacteria) ribosomal subunit. On the basis of results
      obtained with small substrate analogues, isolated 50S subunits seem to be less
      active in peptide bond formation than 70S ribosomes by several orders of
      magnitude, suggesting that the reaction mechanisms on 50S subunits and 70S
      ribosomes may be different. Here we show that with full-size fMet-tRNA(fMet) and
      puromycin or C-puromycin as peptide donor and acceptor substrates, respectively,
      the reaction proceeds as rapidly on 50S subunits as on 70S ribosomes, indicating
      that the intrinsic activity of 50S subunits is not different from that of 70S
      ribosomes. The faster reaction on 50S subunits with fMet-tRNA(fMet), compared
      with oligonucleotide substrate analogues, suggests that full-size transfer RNA in
      the P site is important for maintaining the active conformation of the peptidyl
      transferase centre.

PMID- 16799465
TI  - ORC binding to TRF2 stimulates OriP replication.
AB  - In higher eukaryotes, the origin recognition complex (ORC) lacks sequence
      specific DNA binding, and it remains unclear what other factors specify an origin
      of DNA replication. The Epstein-Barr virus origin of plasmid replication (OriP)
      recruits ORC, but the precise mechanism of ORC recruitment and origin activation
      is not clear. We now show that ORC is recruited selectively to the dyad symmetry
      (DS) region of OriP as a consequence of direct interactions with telomere repeat
      factor 2 (TRF2) and ORC1. TRF-binding sites within DS stimulate replication
      initiation and facilitate ORC recruitment in vitro and in vivo. TRF2, but not
      TRF1 or hRap1, recruits ORC from nuclear extracts. The amino-terminal domain of
      TRF2 associated with a specific region of ORC1 and was necessary for stimulation
      of DNA replication. These results support a model in which TRF2 stimulates OriP
      replication activity by direct binding with ORC subunits.

PMID- 16799466
TI  - Homeostatic regulation of supercoiling sensitivity coordinates transcription of
      the bacterial genome.
AB  - Regulation of cellular growth implies spatiotemporally coordinated programmes of
      gene transcription. A central question, therefore, is how global transcription is
      coordinated in the genome. The growth of the unicellular organism Escherichia
      coli is associated with changes in both the global superhelicity modulated by
      cellular topoisomerase activity and the relative proportions of the abundant DNA
      architectural chromatin proteins. Using a DNA-microarray-based approach that
      combines mutations in the genes of two important chromatin proteins with induced
      changes of DNA superhelicity, we demonstrate that genomic transcription is
      tightly associated with the spatial distribution of supercoiling sensitivity,
      which in turn depends on chromatin proteins. We further demonstrate that
      essential metabolic pathways involved in the maintenance of growth respond
      distinctly to changes of superhelicity. We infer that a homeostatic mechanism
      organizing the supercoiling sensitivity is coordinating the growth-phase
      dependent transcription of the genome.

PMID- 16799467
TI  - Internal ribosome entry sequence-mediated translation initiation triggers
      nonsense-mediated decay.
AB  - In eukaryotes, a surveillance pathway known as nonsense-mediated decay (NMD)
      regulates the abundance of messenger RNAs containing premature termination codons
      (PTCs). In mammalian cells, it has been asserted that the NMD-relevant first
      round of translation is special and involves initiation by a specific protein
      heterodimer, the nuclear cap-binding complex (CBC). Arguing against a requirement
      for CBC-mediated translation initiation, we show that ribosomal recruitment by
      the internal ribosomal entry sequence of the encephalomyocarditis virus triggers
      NMD of a PTC-containing transcript under conditions in which ribosome entry from
      the cap is prohibited. These data generalize the previous model and suggest that
      translation per se, irrespective of how it is initiated, can mediate NMD.

PMID- 16799468
TI  - The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus
      in colorectal cancer.
AB  - Melanoma differentiation associated gene-7 (Mda-7)/IL-24 was previously cloned
      into ZD55 (an adenovirus with E1B55 deleted) to form ZD55-IL-24, which had much
      better antitumor effect than Ad-IL-24. According to its good antitumor
      properties, ZD55-IL-24 has been used in preclinical studies. But ZD55-IL-24 alone
      still could not completely eradicate established tumors in all nude mice. It was
      reported that IL-24 could induce and enhance the activity of tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) (a member of tumor necrosis
      factor (TNF) superfamily). Accordingly, the combined use of ZD55-IL-24 and ZD55
      TRAIL was carried out in this study. Treatment with both ZD55-IL-24 and ZD55
      TRAIL could induce more significant apoptosis in cancer cells in vitro compared
      with ZD55-IL-24 or ZD55-TRAIL alone. The combination of the two replicative
      adenoviruses had better antitumor activity in vivo than that of single oncolytic
      adenovirus and led to complete eradication of xenograft tumors in all treated
      mice. Upregulation of TRAIL was observed in tumor cells infected with ZD55-IL-24
      and studies of the apoptotic cascade regulators indicate that ZD55-IL-24 could
      further enhance the activation of apoptosis through the TNF family of death
      receptors. We demonstrated for the first time the potential therapeutic effect of
      combined ZD55-IL-24 with ZD55-TRAIL for the targeted therapy of cancer.

PMID- 16799469
TI  - Systemic inhibition of tumor growth by soluble Flk-1 gene therapy combined with
      cisplatin.
AB  - Soluble Flk-1, a soluble vascular endothelial growth factor (VEGF) receptor, is a
      potent inhibitor of angiogenesis, which could restrain growth and metastasis of
      some experimental tumors. However, antiangiogenic agents alone cannot eradicate
      tumor completely, and should be combined with other therapy to enhance their
      effects. In this study, we evaluated the antitumor activity of the combination
      therapy in the immunocompetent BALB/c mice bearing H22 hepatoma and Meth A
      fibrosarcoma, respectively. Mice were treated with either msFlk-1 i.m. at 100
      microg/mouse once every 3 days for four times from day 3 after the tumor cell
      injection, cisplatin cycled twice (2 mg/kg i.p. on days 4 and 11 after the tumor
      cell inoculation), or both agents together. Tumor growth and survival time were
      continually observed. Antiangiogenesis in vivo was determined by CD31
      immunohistochemistry. Assessment of apoptotic cells and histological analysis was
      also conducted in tumor tissues. Our results showed that the combination therapy
      could evidently improve antitumor efficacy, including tumor growth suppression,
      mice survival prolongation, tumor cell apoptosis augmentation as well as
      neovascularization inhibition as compared with controls, without serious adverse
      effects. Our data suggest that the combination of DDP with msFlk-1 is more
      effective to suppress tumor growth in mice than either agent alone, and this
      combination regimen showed its potential for future clinical application.

PMID- 16799470
TI  - Dynamic imaging of the immune system: progress, pitfalls and promise.
AB  - Both innate and adaptive immunity are dependent on the migratory capacity of
      myeloid and lymphoid cells. Effector cells of the innate immune system rapidly
      enter infected tissues, whereas sentinel dendritic cells in these sites mobilize
      and transit to lymph nodes. In these and other secondary lymphoid tissues,
      interactions among various cell types promote adaptive humoral and cell-mediated
      immune responses. Recent advances in light microscopy have allowed direct
      visualization of these events in living animals and tissue explants, which allows
      a new appreciation of the dynamics of immune-cell behaviour. In this article, we
      review the basic techniques and the tools used for in situ imaging, as well as
      the limitations and potential artefacts of these methods.

PMID- 16799471
TI  - Self-tolerance of natural killer cells.
AB  - Natural killer (NK) cells, similar to other lymphocytes, acquire tolerance to
      self. This means that NK cells have the potential to attack normal self cells but
      that there are mechanisms to ensure that this does not usually occur. Self
      tolerance is acquired by NK cells during their development, but the underlying
      molecular and cellular mechanisms remain poorly understood. Recent studies have
      produced important new information about NK-cell self-tolerance. Here, we review
      the evidence for and against possible mechanisms of NK-cell self-tolerance, with
      an emphasis on the role of MHC-specific receptors.

PMID- 16799472
TI  - The many paths to p38 mitogen-activated protein kinase activation in the immune
      system.
AB  - Signals emanating from many cell-surface receptors and environmental cues
      converge on mitogen-activated protein kinases (MAPKs), which in turn
      phosphorylate and activate various transcription factors and other molecular
      effectors. Members of the p38 MAPK family, which respond to pro-inflammatory
      cytokines and cellular stresses, are typically activated by serial
      phosphorylation and activation of upstream kinases (the MAPK cascade). In this
      Review, I highlight the recent studies that indicate that p38-subfamily members
      can also be activated by non-canonical mechanisms, at least one of which seems to
      have an important role in antigen-receptor-activated T cells. These alternative
      pathways might have particular relevance for cells that participate in immune and
      inflammatory responses.

PMID- 16799473
TI  - Neutrophil serine proteases: specific regulators of inflammation.
AB  - Neutrophils are essential for host defence against invading pathogens. They
      engulf and degrade microorganisms using an array of weapons that include reactive
      oxygen species, antimicrobial peptides, and proteases such as cathepsin G,
      neutrophil elastase and proteinase 3. As discussed in this Review, the generation
      of mice deficient in these proteases has established a role for these enzymes as
      intracellular microbicidal agents. However, I focus mainly on emerging data
      indicating that, after release, these proteases also contribute to the
      extracellular killing of microorganisms, and regulate non-infectious inflammatory
      processes by activating specific receptors and modulating the levels of
      cytokines.

PMID- 16799474
TI  - The thymus and T-cell commitment: the right niche for Notch?
AB  - The current dogma is that the thymus is colonized by progenitors that retain the
      capacity to generate both T cells and B cells, and that intrathymic Notch
      signalling determines lineage choice so that T cells, rather than B cells,
      develop in the thymus. However, evidence is now accumulating to indicate that, at
      least during fetal life, this is not the case. Rather, it now seems that the
      fetal thymus is colonized by progenitors that have already made the T-cell versus
      B-cell lineage choice. We propose an alternative role for Notch signalling in the
      thymus, which is not to mediate this choice but instead to reveal it by
      supporting further T-cell differentiation in the thymic microenvironment.

PMID- 16799475
TI  - Expression of p14ARF, p15INK4b, p16INK4a, and DCR2 increases during prostate
      cancer progression.
AB  - Prostate carcinoma is a hormonally driven age-related neoplasm. Cellular
      senescence is an age-related process where cells remain metabolically active but
      in a growth-arrested state at the G1 phase. p14(ARF), p15(INK4b), and p16(INK4a),
      which are known to regulate G1 cell cycle arrest, and the tumor necrosis factor
      receptor superfamily member decoy receptor 2 (DCR2), have been recently
      identified as senescence markers. The purpose of this study was to characterize
      and compare the expression of p14(ARF), p15(INK4b), p16(INK4a), and DCR2 in
      tissue microarrays containing cases of normal prostate, nodular hyperplasia,
      prostate intraepithelial neoplasia (PIN), and malignant prostate cancer tissue.
      We performed immunohistochemical staining for p14(ARF), p15(INK4b), p16(INK4a),
      and DCR2 in tissue microarray blocks containing 41 cores of normal prostate, 65
      cores of nodular hyperplasia, 21 cores of PIN, 69 cores of low-grade prostate
      carcinoma, and 42 cores of high-grade prostate carcinoma, derived from 80 cases
      of prostatectomy with adenocarcinomas. We detected positive staining of
      p16(INK4a) in 19% of the PIN, 25% of the low-grade carcinoma, and 43% of the high
      grade carcinoma specimens but none in the normal prostate and nodular hyperplasia
      specimens. Expression of p14(ARF) revealed very high levels of expression in
      normal tissues (83%), nodular hyperplasia (88%), PIN (89%), and cancer cells
      (100%). P15(INK4b) and DCR2 were found positive in 81 and 33% normal, 46 and 10%
      nodular hyperplasia, 74 and 36% PIN tissues, 87 and 89% low-grade carcinomas, and
      100 and 93% high-grade carcinomas. There is an increased protein expression of
      senescence-associated molecular markers, indicating that cellular senescence
      might play a role in prostate carcinoma. Because p16(INK4a)-positive cells were
      detected only in premalignant lesions and carcinomas but not in normal or benign
      tissues, p16(INK4a) may aid in the diagnosis of PIN and prostate cancer in
      difficult cases.

PMID- 16799477
TI  - Lymphatic microvessel density as prognostic marker in colorectal cancer.
AB  - Lymph node metastases is an important prognostic indicator for disease
      progression and crucial for therapeutic strategies in the work-up of colorectal
      carcinoma. In this study, we investigated tumor lymphangiogenesis and vascular
      endothelial growth factor (VEGF) expression as predictive markers for the risk of
      lymph node metastasis and their relation to other prognostic parameters in
      colorectal carcinoma. Resected colorectal carcinomas from 90 patients were
      examined, including 30 patients without lymph node metastases, 30 with only lymph
      node metastases, and 30 with liver metastases. Cases were immunostained for CD31,
      D2-40, and VEGF. Positivity stained microvessels were counted in densely
      vascular/lymphatic foci (hot spots) at x 400 field (=0.17 mm2). Intensity of
      staining for VEGF was scored on a two-tiered scale. D2-40 lymphatic microvessel
      density demonstrated significant correlation with CD31 counts (20+/-9 vs 18+/
      6/0.17 mm2 field, P<0.05) and VEGF expression (P<0.01). VEGF was expressed in
      61/90 (67%) cases. D2-40 identified lymphatic tumor invasion in 48/90 patients,
      which was greater than CD31 (37/90) and hematoxylin and eosin (H&E) (31/90).
      There was a positive significant correlation of D2-40, CD31 counts, and VEGF
      expression with the presence of lymphovascular invasion and lymph node metastases
      (P<0.05). D2-40 lymphatic microvessel density correlated significantly with depth
      of invasion (pT), positive vascular pedicle lymph nodes and liver metastases
      (P<0.05). In conclusion, D2-40 lymphatic microvessel density showed prognostic
      significance with positive correlation with lymphovascular invasion, pT, and
      metastases to lymph nodes and liver. Immunostaining with D2-40 enhances the
      detection of lymphatic invasion relative to H&E staining and the endothelial
      marker, CD31.

PMID- 16799476
TI  - BRAF and NRAS mutations in spitzoid melanocytic lesions.
AB  - BRAF mutations are common events in a variety of melanocytic nevi and primary
      cutaneous melanomas. We have previously found BRAF mutations in 82% of nevi,
      consisting of congenital, common acquired and dysplastic types, and 33% of
      primary cutaneous melanomas other than the spitzoid type, similar to other
      published reports. A small number of studies have evaluated Spitz nevi and have
      failed to detect any lesions possessing a BRAF mutation. Only one study included
      categories of atypical Spitz nevus and borderline lesions suspected to be
      spitzoid melanomas, along with classic Spitz nevi and spitzoid melanomas. We
      examined a spectrum of spitzoid lesions that included 48 Spitz nevi, some with
      atypical features, seven atypical (borderline) Spitz tumors, and 13 spitzoid
      melanomas. BRAF mutations were detected in 12 of 68 spitzoid lesions, of which
      two were spitzoid melanomas and 10 were Spitz nevi. Five of the 10 Spitz nevi
      with BRAF mutations were altered by more than usual cytologic atypia and/or
      architectural atypia overlapping with dysplastic nevi, or
      irritation/inflammation; one desmoplastic Spitz nevus had a BRAF mutation. These
      results indicate that a small subset of Spitz nevi, some with atypical histologic
      features, possess BRAF mutations. Therefore, the BRAF mutational status does not
      separate all Spitz nevi from spitzoid melanomas and non-Spitz types of
      melanocytic proliferations, contrary to previous reports.

PMID- 16799478
TI  - Immunohistochemical detection of p16INK4a in dysplastic lesions of the oral
      cavity.
AB  - Significant intra- and interobserver variability exists in diagnosing and grading
      oral epithelial dysplasia. Mutations in the tumor-suppressor gene p16 are common
      in oral cavity dysplastic lesions, but whether immunohistochemical detection of
      the gene product p16(INK4a) (p16) can be used as a reliable biomarker for
      dysplasia is unclear. In total, 119 biopsy specimens representing various oral
      cavity sites and degrees of dysplasia were retrieved from the pathology files of
      Emory University Hospital. Formalin-fixed, paraffin-embedded sections were
      stained with hematoxylin and eosin (H&E) and with a monoclonal antibody to p16
      (LabVision Corporation, Clone JC2). A blinded review of the H&E slides and the
      pattern and degree of p16 expression was independently performed by two
      pathologists. A consensus was obtained when diagnoses differed. Morphologic
      diagnoses were then compared to p16 immunohistochemical expression. Overall,
      61/119 (51%) cases showed no p16 immunoreactivity, including 12/33 (36%) cases of
      no dysplasia, 11/28 (39%) cases of mild dysplasia, and 38/58 (66%) cases of
      moderate/severe dysplasia. The remaining cases showed p16 expression limited to
      the basal and suprabasal nuclei and generally confined to the lower one-third of
      the epithelium. A logistic regression model showed a trend toward absent p16
      expression with increasing severity of dysplasia (P=0.006). Decreased expression
      of p16 in dysplastic lesions, as found in this study, may reflect the biologic
      events involving loss of p16 gene function in the pathogenesis of oral cancer.
      Our findings suggest that p16 immunohistochemistry is not helpful in
      differentiating dysplastic from nondysplastic mucosa in oral cavity biopsies, and
      thus is not a reliable biomarker for use in routine clinical practice.

PMID- 16799479
TI  - Expression of the ELAV-like protein HuR in human colon cancer: association with
      tumor stage and cyclooxygenase-2.
AB  - There is growing body of evidence that post-translational events contribute-in
      addition to genetic changes-to the progression of malignant tumors. These post
      translational alterations may provide targets for new therapeutic approaches. The
      ELAV-like protein HuR stabilizes a group of cellular mRNAs which contain AU-rich
      elements in their 3' untranslated region. To investigate a possible contribution
      of post-translational changes to the progression of colon cancer and to
      overexpression of COX-2, we studied expression of HuR and COX-2 a cohort of
      colorectal adenocarcinomas and in colon cancer cell lines. All cell lines showed
      an expression of HuR mRNA and protein. In tumor tissue of colon carcinomas we
      observed two different staining patterns of HuR: A nuclear expression in 98% as
      well as an additional cytoplasmic expression in 53% of cases. COX-2 was expressed
      in 63% of carcinomas. Cytoplasmic expression of HuR was significantly associated
      with increased COX-2 expression as well as with high tumor stage. In univariate
      Kaplan-Meier analysis, grading, tumor stage and nodal status but not HuR or COX-2
      expression were prognostic factors for overall survival. Our results suggest that
      the overexpression of HuR in colon cancer may be part of a regulatory pathway
      that controls the mRNA stability of cyclooxygenase-2 and provides an interesting
      example for a contribution of a dysregulation of mRNA stability to the
      progression of colorectal cancer. Based on our results, further studies are
      necessary to investigate whether HuR might be a potential target for a molecular
      tumor therapy.

PMID- 16799480
TI  - Fabry disease: a morphologic study of 11 cases.
AB  - Fabry disease is a metabolic disorder caused by the genetic deficiency of alpha
      galactosidase A. Deposition of glycosphingolipids in podocytes, endothelial
      cells, and other cell types leads to formation of myelin-like inclusions, which
      are the hallmark of the disease. In most untreated males, the disorder progresses
      to end-stage kidney disease. Fabry disease is rare, and no renal biopsy series
      focusing on pathologic findings has been published in the past 25 years. We
      retrieved kidney biopsies diagnosed with Fabry disease from our files, and
      reviewed clinical data as well as the light and electron microscopy. In total, 11
      patients were identified: six male subjects aged 17-43 years and five female
      subjects aged 30-73 years. On average, male patients presented more than 10 years
      earlier then female patients. A total of 10 patients had proteinuria, two with
      the nephrotic syndrome. Four male and three female patients had decreased renal
      function. Light microscopy showed vacuolization of the podocyte cytoplasm and
      variable glomerular sclerosis. Older patients and males had more advanced
      glomerular and interstitial sclerosis, but three of the five female patients also
      had advanced renal disease. Electron microscopy showed the characteristic myelin
      like inclusions most prominently in the podocyte cytoplasm. Seven patients also
      had podocyte foot process effacement. A second type of deposit, unexpected and
      conspicuous, was identified in three males, and found to be associated with
      glomerular basement membrane duplications. These deposits were composed of
      layered membrane-like material, and therefore morphologically distinct from
      myelin-like inclusions. They probably represent remnants of damaged endothelial
      cells.

PMID- 16799481
TI  - Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma.
AB  - Human pituitary tumour-transforming gene 1 or hPTTG1 is a proto-oncogene that
      codes for securin, a protein involved in sister chromatid separation. Based on
      previous microarray data, we studied the expression of hPTTG1/securin in
      melanocytic lesions. In contrast to nevi and radial growth phase melanomas,
      securin was expressed by scattered cells in the vertical growth phase, suggesting
      a role in tumour progression. In a series of 29 nodular and 29 superficial
      spreading melanomas, matched for all histological prognostic parameters, securin
      expression was significantly correlated with the nodular subtype (P=0.018) and
      not related to thickness. In other cancers, hPTTG1 is involved in various
      oncogenic pathways, including induction of neovascularisation and aneuploidy, and
      inhibition of p53 activity. We found coexpression of securin with wild-type p53
      in the same neoplastic cells in a minority of melanomas. Expression of securin
      was significantly correlated with the extent of aneuploidy but not with basic
      fibroblast growth factor immunoreactivity or microvessel density. DNA cytometry
      revealed that nuclei-overexpressing securin frequently showed tetraploidy or
      aneuploidy. Our data show that hPTTG1 is frequently overexpressed in nodular
      melanoma, and suggest that hPTTG1 may act as an oncogene in the vertical growth
      phase, either by inhibiting anaphase, thereby causing aneuploidy and genomic
      instability, or by modulating the function of p53, thereby impairing apoptosis.

PMID- 16799546
TI  - Why our readers should concern themselves with their patients' lifestyle and
      diet.

PMID- 16799548
TI  - Proteolytic activity monitored by fluorescence resonance energy transfer through
      quantum-dot-peptide conjugates.
AB  - Proteases are enzymes that catalyse the breaking of specific peptide bonds in
      proteins and polypeptides. They are heavily involved in many normal biological
      processes as well as in diseases, including cancer, stroke and infection. In
      fact, proteolytic activity is sometimes used as a marker for some cancer types.
      Here we present luminescent quantum dot (QD) bioconjugates designed to detect
      proteolytic activity by fluorescence resonance energy transfer. To achieve this,
      we developed a modular peptide structure which allowed us to attach dye-labelled
      substrates for the proteases caspase-1, thrombin, collagenase and chymotrypsin to
      the QD surface. The fluorescence resonance energy transfer efficiency within
      these nanoassemblies is easily controlled, and proteolytic assays were carried
      out under both excess enzyme and excess substrate conditions. These assays
      provide quantitative data including enzymatic velocity, Michaelis-Menten kinetic
      parameters, and mechanisms of enzymatic inhibition. We also screened a number of
      inhibitory compounds against the QD-thrombin conjugate. This technology is not
      limited to sensing proteases, but may be amenable to monitoring other enzymatic
      modifications.

PMID- 16799549
TI  - Large-scale optical-field measurements with geometric fibre constructs.
AB  - Optical fields are measured using sequential arrangements of optical components
      such as lenses, filters, and beam splitters in conjunction with planar arrays of
      point detectors placed on a common axis. All such systems are constrained in
      terms of size, weight, durability and field of view. Here a new, geometric
      approach to optical-field measurements is presented that lifts some of the
      aforementioned limitations and, moreover, enables access to optical information
      on unprecedented length and volume scales. Tough polymeric photodetecting fibres
      drawn from a preform are woven into light-weight, low-optical-density, two- and
      three-dimensional constructs that measure the amplitude and phase of an
      electromagnetic field on very large areas. First, a three-dimensional spherical
      construct is used to measure the direction of illumination over 4pi steradians.
      Second, an intensity distribution is measured by a planar array using a
      tomographic algorithm. Finally, both the amplitude and phase of an optical wave
      front are acquired with a dual-plane construct. Hence, the problem of optical
      field measurement is transformed from one involving the choice and placement of
      lenses and detector arrays to that of designing geometrical constructions of
      polymeric, light-sensitive fibres.

PMID- 16799550
TI  - Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain
      topology.
AB  - Protein ubiquitination regulates many cellular processes, including protein
      degradation, signal transduction, DNA repair and cell division. In the classical
      model, a uniform polyubiquitin chain that is linked through Lys 48 is required
      for recognition and degradation by the 26S proteasome. Here, we used a
      reconstituted system and quantitative mass spectrometry to demonstrate that
      cyclin B1 is modified by ubiquitin chains of complex topology, rather than by
      homogeneous Lys 48-linked chains. The anaphase-promoting complex was found to
      attach monoubiquitin to multiple lysine residues on cyclin B1, followed by poly
      ubiquitin chain extensions linked through multiple lysine residues of ubiquitin
      (Lys 63, Lys 11 and Lys 48). These heterogeneous ubiquitin chains were sufficient
      for binding to ubiquitin receptors, as well as for degradation by the 26S
      proteasome, even when they were synthesized with mutant ubiquitin that lacked Lys
      48. Together, our observations expand the context of what can be considered to be
      a sufficient degradation signal and provide unique insights into the mechanisms
      of substrate ubiquitination.

PMID- 16799551
TI  - Autophagic and tumour suppressor activity of a novel Beclin1-binding protein
      UVRAG.
AB  - Autophagy, the degradation of cytoplasmic components, is an evolutionarily
      conserved homeostatic process involved in environmental adaptation, lifespan
      determination and tumour development. The tumor suppressor Beclin1 is part of the
      PI(3) kinase class III (PI(3)KC3) lipid-kinase complex that induces autophagy.
      The autophagic activity of the Beclin1-PI(3)KC3 complex, however, is suppressed
      by Bcl-2. Here, we report the identification of a novel coiled-coil UV
      irradiation resistance-associated gene (UVRAG) as a positive regulator of the
      Beclin1-PI(3)KC3 complex. UVRAG, a tumour suppressor candidate that is
      monoallelically mutated at high frequency in human colon cancers, associates with
      the Beclin1-Bcl-2-PI(3)KC3 multiprotein complex, where UVRAG and Beclin1
      interdependently induce autophagy. UVRAG-mediated activation of the Beclin1
      PI(3)KC3 complex promotes autophagy and also suppresses the proliferation and
      tumorigenicity of human colon cancer cells. These results identify UVRAG as an
      essential component of the Beclin1-PI(3)KC3 lipid kinase complex that is an
      important signalling checkpoint for autophagy and tumour-cell growth.

PMID- 16799552
TI  - Asymmetric division and cosegregation of template DNA strands in adult muscle
      satellite cells.
AB  - Satellite cells assure postnatal skeletal muscle growth and repair. Despite
      extensive studies, their stem cell character remains largely undefined. Using
      pulse-chase labelling with BrdU to mark the putative stem cell niche, we identify
      a subpopulation of label-retaining satellite cells during growth and after
      injury. Strikingly, some of these cells display selective template-DNA strand
      segregation during mitosis in the muscle fibre in vivo, as well as in culture
      independent of their niche, indicating that genomic DNA strands are
      nonequivalent. Furthermore, we demonstrate that the asymmetric cell-fate
      determinant Numb segregates selectively to one daughter cell during mitosis and
      before differentiation, suggesting that Numb is associated with self-renewal.
      Finally, we show that template DNA cosegregates with Numb in label-retaining
      cells that express the self-renewal marker Pax7. The cosegregation of 'immortal'
      template DNA strands and their link with the asymmetry apparatus has important
      implications for stem cell biology and cancer.

PMID- 16799553
TI  - Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli.
AB  - Nonribosomal peptides (NRPs) are a class of microbial secondary metabolites that
      have a wide variety of medicinally important biological activities, such as
      antibiotic (vancomycin), immunosuppressive (cyclosporin A), antiviral (luzopeptin
      A) and antitumor (echinomycin and triostin A) activities. However, many microbes
      are not amenable to cultivation and require time-consuming empirical optimization
      of incubation conditions for mass production of desired secondary metabolites for
      clinical and commercial use. Therefore, a fast, simple system for heterologous
      production of natural products is much desired. Here we show the first example of
      the de novo total biosynthesis of biologically active forms of heterologous NRPs
      in Escherichia coli. Our system can serve not only as an effective and flexible
      platform for large-scale preparation of natural products from simple carbon and
      nitrogen sources, but also as a general tool for detailed characterizations and
      rapid engineering of biosynthetic pathways for microbial syntheses of novel
      compounds and their analogs.

PMID- 16799554
TI  - Coupling ligand structure to specific conformational switches in the beta2
      adrenoceptor.
AB  - G protein-coupled receptors (GPCRs) regulate a wide variety of physiological
      functions in response to structurally diverse ligands ranging from cations and
      small organic molecules to peptides and glycoproteins. For many GPCRs,
      structurally related ligands can have diverse efficacy profiles. To investigate
      the process of ligand binding and activation, we used fluorescence spectroscopy
      to study the ability of ligands having different efficacies to induce a specific
      conformational change in the human beta2-adrenoceptor (beta2-AR). The 'ionic
      lock' is a molecular switch found in rhodopsin-family GPCRs that has been
      proposed to link the cytoplasmic ends of transmembrane domains 3 and 6 in the
      inactive state. We found that most partial agonists were as effective as full
      agonists in disrupting the ionic lock. Our results show that disruption of this
      important molecular switch is necessary, but not sufficient, for full activation
      of the beta2-AR.

PMID- 16799555
TI  - Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal
      fluid in vivo.
AB  - Certain disease states are characterized by disturbances in production,
      accumulation or clearance of protein. In Alzheimer disease, accumulation of
      amyloid-beta (Abeta) in the brain and disease-causing mutations in amyloid
      precursor protein or in enzymes that produce Abeta indicate dysregulation of
      production or clearance of Abeta. Whether dysregulation of Abeta synthesis or
      clearance causes the most common form of Alzheimer disease (sporadic, >99% of
      cases), however, is not known. Here, we describe a method to determine the
      production and clearance rates of proteins within the human central nervous
      system (CNS). We report the first measurements of the fractional production and
      clearance rates of Abeta in vivo in the human CNS to be 7.6% per hour and 8.3%
      per hour, respectively. This method may be used to search for novel biomarkers of
      disease, to assess underlying differences in protein metabolism that contribute
      to disease and to evaluate treatments in terms of their pharmacodynamic effects
      on proposed disease-causing pathways.

PMID- 16799556
TI  - Sensitive mutation detection in heterogeneous cancer specimens by massively
      parallel picoliter reactor sequencing.
AB  - The sensitivity of conventional DNA sequencing in tumor biopsies is limited by
      stromal contamination and by genetic heterogeneity within the cancer. Here, we
      show that microreactor-based pyrosequencing can detect rare cancer-associated
      sequence variations by independent and parallel sampling of multiple
      representatives of a given DNA fragment. This technology can thereby facilitate
      accurate molecular diagnosis of heterogeneous cancer specimens and enable patient
      selection for targeted cancer therapies.

PMID- 16799557
TI  - VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin
      synthesis.
AB  - Vascular endothelial growth factor (VEGF) exerts crucial functions during
      pathological angiogenesis and normal physiology. We observed increased hematocrit
      (60-75%) after high-grade inhibition of VEGF by diverse methods, including
      adenoviral expression of soluble VEGF receptor (VEGFR) ectodomains, recombinant
      VEGF Trap protein and the VEGFR2-selective antibody DC101. Increased production
      of red blood cells (erythrocytosis) occurred in both mouse and primate models,
      and was associated with near-complete neutralization of VEGF corneal micropocket
      angiogenesis. High-grade inhibition of VEGF induced hepatic synthesis of
      erythropoietin (Epo, encoded by Epo) >40-fold through a HIF-1alpha-independent
      mechanism, in parallel with suppression of renal Epo mRNA. Studies using
      hepatocyte-specific deletion of the Vegfa gene and hepatocyte-endothelial cell
      cocultures indicated that blockade of VEGF induced hepatic Epo by interfering
      with homeostatic VEGFR2-dependent paracrine signaling involving interactions
      between hepatocytes and endothelial cells. These data indicate that VEGF is a
      previously unsuspected negative regulator of hepatic Epo synthesis and
      erythropoiesis and suggest that levels of Epo and erythrocytosis could represent
      noninvasive surrogate markers for stringent blockade of VEGF in vivo.

PMID- 16799558
TI  - Crystal structure and mechanism of human lysine-specific demethylase-1.
AB  - The reversible methylation of specific lysine residues in histone tails is
      crucial in epigenetic gene regulation. LSD1, the first known lysine-specific
      demethylase, selectively removes monomethyl and dimethyl, but not trimethyl
      modifications of Lys4 or Lys9 of histone-3. Here, we present the crystal
      structure of LSD1 at 2.9-A resolution. LSD1 forms a highly asymmetric, closely
      packed domain structure from which a long helical 'tower' domain protrudes. The
      active site cavity is spacious enough to accommodate several residues of the
      histone tail substrate, but does not appear capable of recognizing the different
      methylation states of the substrate lysine. This supports the hypothesis that
      trimethylated lysine is chemically rather than sterically discriminated. We
      present a biochemical analysis of LSD1 mutants that identifies crucial residues
      in the active site cavity and shows the importance of the SWIRM and tower domains
      for catalysis.

PMID- 16799559
TI  - Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin
      D(28K).
AB  - Calbindin-D(28K) is a Ca2+-binding protein, performing roles as both a calcium
      buffer and calcium sensor. The NMR solution structure of Ca2+-loaded calbindin
      D(28K) reveals a single, globular fold consisting of six distinct EF-hand
      subdomains, which coordinate Ca2+ in loops on EF1, EF3, EF4 and EF5. Target
      peptides from Ran-binding protein M and myo-inositol monophosphatase, along with
      a new target from procaspase-3, are shown to interact with the protein on a
      surface comprised of alpha5 (EF3), alpha8 (EF4) and the EF2-EF3 and EF4-EF5
      loops. Fluorescence experiments reveal that calbindin-D(28K) adopts discrete
      hydrophobic states as it binds Ca2+. The structure, binding interface and
      hydrophobic characteristics of Ca2+-loaded calbindin-D(28K) provide the first
      detailed insights into how this essential protein may function. This structure is
      one of the largest high-resolution NMR structures and the largest monomeric EF
      hand protein to be solved to date.

PMID- 16799560
TI  - Separate RNA-binding surfaces on the multifunctional La protein mediate
      distinguishable activities in tRNA maturation.
AB  - By sequence-specific binding to 3' UUU-OH, the La protein shields precursor (pre)
      RNAs from 3' end digestion and is required to protect defective pre-transfer RNAs
      from decay. Although La is comprised of a La motif and an RNA-recognition motif
      (RRM), a recent structure indicates that the RRM beta-sheet surface is not
      involved in UUU-OH recognition, raising questions as to its function.
      Progressively defective suppressor tRNAs in Schizosaccharomyces pombe reveal
      differential sensitivities to La and Rrp6p, a 3' exonuclease component of pre
      tRNA decay. 3' end protection is compromised by mutations to the La motif but not
      the RRM surface. The most defective pre-tRNAs require a second activity of La, in
      addition to 3' protection, that requires an intact RRM surface. The two
      activities of La in tRNA maturation map to its two conserved RNA-binding surfaces
      and suggest a modular model that has implications for its other ligands.

PMID- 16799561
TI  - Ancient evolutionary origin of diversified variable regions demonstrated by
      crystal structures of an immune-type receptor in amphioxus.
AB  - Although the origins of genes encoding the rearranging binding receptors remain
      obscure, it is predicted that their ancestral forms were nonrearranging
      immunoglobulin-type domains. Variable region-containing chitin-binding proteins
      (VCBPs) are diversified immune-type molecules found in amphioxus (Branchiostoma
      floridae), an invertebrate that diverged early in deuterostome phylogeny. To
      study the potential evolutionary relationships between VCBPs and vertebrate
      adaptive immune receptors, we solved the structures of both a single V-type
      domain (to 1.15 A) and a pair of V-type domains (to 1.85 A) from VCBP3. The
      deduced structures show integral features of the ancestral variable-region fold
      as well as unique features of variable-region pairing in molecules that may
      reflect characteristics of ancestral forms of diversified immune receptors found
      in modern-day vertebrates.

PMID- 16799562
TI  - The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell
      development, survival and function.
AB  - The kinase TAK1 is critical for innate and B cell immunity. The function of TAK1
      in T cells is unclear, however. We show here that T cell-specific deletion of the
      gene encoding TAK1 resulted in reduced development of thymocytes, especially of
      regulatory T cells expressing the transcription factor Foxp3. In mature
      thymocytes, TAK1 was required for interleukin 7-mediated survival and T cell
      receptor-dependent activation of transcription factor NF-kappaB and the kinase
      Jnk. In effector T cells, TAK1 was dispensable for T cell receptor-dependent NF
      kappaB activation and cytokine production, but was important for proliferation
      and activation of the kinase p38 in response to interleukins 2, 7 and 15. Thus,
      TAK1 is essential for the integration of T cell receptor and cytokine signals to
      regulate the development, survival and function of T cells.

PMID- 16799563
TI  - An ARC/Mediator subunit required for SREBP control of cholesterol and lipid
      homeostasis.
AB  - The sterol regulatory element binding protein (SREBP) family of transcription
      activators are critical regulators of cholesterol and fatty acid homeostasis. We
      previously demonstrated that human SREBPs bind the CREB-binding protein
      (CBP)/p300 acetyltransferase KIX domain and recruit activator-recruited co-factor
      (ARC)/Mediator co-activator complexes through unknown mechanisms. Here we show
      that SREBPs use the evolutionarily conserved ARC105 (also called MED15) subunit
      to activate target genes. Structural analysis of the SREBP-binding domain in
      ARC105 by NMR revealed a three-helix bundle with marked similarity to the
      CBP/p300 KIX domain. In contrast to SREBPs, the CREB and c-Myb activators do not
      bind the ARC105 KIX domain, although they interact with the CBP KIX domain,
      revealing a surprising specificity among structurally related activator-binding
      domains. The Caenorhabditis elegans SREBP homologue SBP-1 promotes fatty acid
      homeostasis by regulating the expression of lipogenic enzymes. We found that,
      like SBP-1, the C. elegans ARC105 homologue MDT-15 is required for fatty acid
      homeostasis, and show that both SBP-1 and MDT-15 control transcription of genes
      governing desaturation of stearic acid to oleic acid. Notably, dietary addition
      of oleic acid significantly rescued various defects of nematodes targeted with
      RNA interference against sbp-1 and mdt-15, including impaired intestinal fat
      storage, infertility, decreased size and slow locomotion, suggesting that
      regulation of oleic acid levels represents a physiologically critical function of
      SBP-1 and MDT-15. Taken together, our findings demonstrate that ARC105 is a key
      effector of SREBP-dependent gene regulation and control of lipid homeostasis in
      metazoans.

PMID- 16799564
TI  - Notch signalling regulates stem cell numbers in vitro and in vivo.
AB  - The hope of developing new transplantation therapies for degenerative diseases is
      limited by inefficient stem cell growth and immunological incompatibility with
      the host. Here we show that Notch receptor activation induces the expression of
      the specific target genes hairy and enhancer of split 3 (Hes3) and Sonic hedgehog
      (Shh) through rapid activation of cytoplasmic signals, including the
      serine/threonine kinase Akt, the transcription factor STAT3 and mammalian target
      of rapamycin, and thereby promotes the survival of neural stem cells. In both
      murine somatic and human embryonic stem cells, these positive signals are opposed
      by a control mechanism that involves the p38 mitogen-activated protein kinase.
      Transient administration of Notch ligands to the brain of adult rats increases
      the numbers of newly generated precursor cells and improves motor skills after
      ischaemic injury. These data indicate that stem cell expansion in vitro and in
      vivo, two central goals of regenerative medicine, may be achieved by Notch
      ligands through a pathway that is fundamental to development and cancer.

PMID- 16799565
TI  - Ovulated oocytes in adult mice derive from non-circulating germ cells.
AB  - Decades of research in reproductive biology have led to the generally accepted
      belief that in female mammals, all surviving germ cells enter meiosis at the end
      of fetal development and as a result, the postnatal ovary harbours a limited
      supply of oocytes that cannot be replenished or regenerated if lost to injury or
      disease. However, recent reports have challenged this view, suggesting instead
      that oocyte production is maintained through continual seeding of the ovary by
      circulating, bone-marrow-derived germ cells. To test directly the physiological
      relevance of circulating cells for female fertility, we established
      transplantation and parabiotic mouse models to assess the capacity of circulating
      bone marrow cells to generate ovulated oocytes, both in the steady state and
      after induced damage. Our studies showed no evidence that bone marrow cells, or
      any other normally circulating cells, contribute to the formation of mature,
      ovulated oocytes. Instead, cells that travelled to the ovary through the
      bloodstream exhibited properties characteristic of committed blood leukocytes.

PMID- 16799566
TI  - Assembly dynamics of microtubules at molecular resolution.
AB  - Microtubules are highly dynamic protein polymers that form a crucial part of the
      cytoskeleton in all eukaryotic cells. Although microtubules are known to self
      assemble from tubulin dimers, information on the assembly dynamics of
      microtubules has been limited, both in vitro and in vivo, to measurements of
      average growth and shrinkage rates over several thousands of tubulin subunits. As
      a result there is a lack of information on the sequence of molecular events that
      leads to the growth and shrinkage of microtubule ends. Here we use optical
      tweezers to observe the assembly dynamics of individual microtubules at molecular
      resolution. We find that microtubules can increase their overall length almost
      instantaneously by amounts exceeding the size of individual dimers (8 nm). When
      the microtubule-associated protein XMAP215 (ref. 6) is added, this effect is
      markedly enhanced and fast increases in length of about 40-60 nm are observed.
      These observations suggest that small tubulin oligomers are able to add directly
      to growing microtubules and that XMAP215 speeds up microtubule growth by
      facilitating the addition of long oligomers. The achievement of molecular
      resolution on the microtubule assembly process opens the way to direct studies of
      the molecular mechanism by which the many recently discovered microtubule end
      binding proteins regulate microtubule dynamics in living cells.

PMID- 16799567
TI  - Endothelial tubes assemble from intracellular vacuoles in vivo.
AB  - The formation of epithelial tubes is crucial for the proper development of many
      different tissues and organs, and occurs by means of a variety of different
      mechanisms. Morphogenesis of seamless, properly patterned endothelial tubes is
      essential for the development of a functional vertebrate circulatory system, but
      the mechanism of vascular lumenization in vivo remains unclear. Evidence dating
      back more than 100 years has hinted at an important function for endothelial
      vacuoles in lumen formation. More than 25 years ago, in some of the first
      endothelial cell culture experiments in vitro, Folkman and Haudenschild described
      "longitudinal vacuoles" that "appeared to be extruded and connected from one cell
      to the next", observations confirmed and extended by later studies in vitro
      showing that intracellular vacuoles arise from integrin-dependent and cdc42/Rac1
      dependent pinocytic events downstream of integrin-extracellular-matrix signalling
      interactions. Despite compelling data supporting a model for the assembly of
      endothelial tubes in vitro through the formation and fusion of vacuoles,
      conclusive evidence in vivo has been lacking, primarily because of difficulties
      associated with imaging the dynamics of subcellular endothelial vacuoles deep
      within living animals. Here we use high-resolution time-lapse two-photon imaging
      of transgenic zebrafish to examine how endothelial tubes assemble in vivo,
      comparing our results with time-lapse imaging of human endothelial-cell tube
      formation in three-dimensional collagen matrices in vitro. Our results provide
      strong support for a model in which the formation and intracellular and
      intercellular fusion of endothelial vacuoles drives vascular lumen formation.

PMID- 16799568
TI  - Mesodermal Wnt2b signalling positively regulates liver specification.
AB  - Endodermal organs such as the lung, liver and pancreas emerge at precise
      locations along the primitive gut tube. Although several signalling pathways have
      been implicated in liver formation, so far no single gene has been identified
      that exclusively regulates liver specification. In zebrafish, the onset of liver
      specification is marked by the localized endodermal expression of hhex and prox1
      at 22 hours post fertilization. Here we used a screen for mutations affecting
      endodermal organ morphogenesis to identify a unique phenotype: prometheus (prt)
      mutants exhibit profound, though transient, defects in liver specification.
      Positional cloning reveals that prt encodes a previously unidentified Wnt2b
      homologue. prt/wnt2bb is expressed in restricted bilateral domains in the lateral
      plate mesoderm directly adjacent to the liver-forming endoderm. Mosaic analyses
      show the requirement for Prt/Wnt2bb in the lateral plate mesoderm, in agreement
      with the inductive properties of Wnt signalling. Taken together, these data
      reveal an unexpected positive role for Wnt signalling in liver specification, and
      indicate a possible common theme for the localized formation of endodermal organs
      along the gut tube.

PMID- 16799569
TI  - Enzymatic activation of voltage-gated potassium channels.
AB  - Voltage-gated ion channels in excitable nerve, muscle, and endocrine cells
      generate electric signals in the form of action potentials. However, they are
      also present in non-excitable eukaryotic cells and prokaryotes, which raises the
      question of whether voltage-gated channels might be activated by means other than
      changing the voltage difference between the solutions separated by the plasma
      membrane. The search for so-called voltage-gated channel activators is motivated
      in part by the growing importance of such agents in clinical pharmacology. Here
      we report the apparent activation of voltage-gated K+ (Kv) channels by a
      sphingomyelinase.

PMID- 16799570
TI  - ATM stabilizes DNA double-strand-break complexes during V(D)J recombination.
AB  - The ATM (ataxia-telangiectasia mutated) protein kinase mediates early cellular
      responses to DNA double-strand breaks (DSBs) generated during metabolic processes
      or by DNA-damaging agents. ATM deficiency leads to ataxia-telangiectasia, a
      disease marked by lymphopenia, genomic instability and an increased
      predisposition to lymphoid malignancies with chromosomal translocations involving
      lymphocyte antigen receptor loci. ATM activates cell-cycle checkpoints and can
      induce apoptosis in response to DNA DSBs. However, defects in these pathways of
      the DNA damage response cannot fully account for the phenotypes of ATM
      deficiency. Here, we show that ATM also functions directly in the repair of
      chromosomal DNA DSBs by maintaining DNA ends in repair complexes generated during
      lymphocyte antigen receptor gene assembly. When coupled with the cell-cycle
      checkpoint and pro-apoptotic activities of ATM, these findings provide a
      molecular explanation for the increase in lymphoid tumours with translocations
      involving antigen receptor loci associated with ataxia-telangiectasia.

PMID- 16799571
TI  - Atom-by-atom analysis of global downhill protein folding.
AB  - Protein folding is an inherently complex process involving coordination of the
      intricate networks of weak interactions that stabilize native three-dimensional
      structures. In the conventional paradigm, simple protein structures are assumed
      to fold in an all-or-none process that is inaccessible to experiment. Existing
      experimental methods therefore probe folding mechanisms indirectly. A widely used
      approach interprets changes in protein stability and/or folding kinetics, induced
      by engineered mutations, in terms of the structure of the native protein. In
      addition to limitations in connecting energetics with structure, mutational
      methods have significant experimental uncertainties and are unable to map complex
      networks of interactions. In contrast, analytical theory predicts small barriers
      to folding and the possibility of downhill folding. These theoretical predictions
      have been confirmed experimentally in recent years, including the observation of
      global downhill folding. However, a key remaining question is whether downhill
      folding can indeed lead to the high-resolution analysis of protein folding
      processes. Here we show, with the use of nuclear magnetic resonance (NMR), that
      the downhill protein BBL from Escherichia coli unfolds atom by atom starting from
      a defined three-dimensional structure. Thermal unfolding data on 158 backbone and
      side-chain protons out of a total of 204 provide a detailed view of the
      structural events during folding. This view confirms the statistical nature of
      folding, and exposes the interplay between hydrogen bonding, hydrophobic forces,
      backbone conformation and side-chain entropy. From the data we also obtain a map
      of the interaction network in this protein, which reveals the source of folding
      cooperativity. Our approach can be extended to other proteins with marginal
      barriers (less than 3RT), providing a new tool for the study of protein folding.

PMID- 16799601
TI  - Classification and diagnosis of mastocytosis: current status.
AB  - Mastocytosis is a disease characterized by an abnormal increase in mast cells.
      Manifestations of the disease are provoked in large part by the resultant
      increase in mast cell-derived mediators, which have a variety of local and
      systemic effects. Mastocytosis is variable in respect to the organ systems
      involved, clinical manifestations, and association with hematologic diseases.
      This has suggested the need for an improved classification scheme to allow
      assessment of prognosis and therapy. The heterogeneity of the disease patterns in
      mastocytosis strongly suggests that more than one biologic lesion may occur in
      the developmental sequence that leads to placement of mature mast cells in
      tissues.

PMID- 16799602
TI  - Systemic mastocytosis: retrospective review of a decade's clinical experience at
      the Brigham and Women's Hospital.
AB  - The clinical experience with a group of 21 patients with systemic mastocytosis
      followed at our institution is summarized. Cutaneous and gastrointestinal
      symptoms and findings were the most prominent chronic manifestations; episodic
      vascular collapse was the most dramatic acute event. All patients had indolent
      mastocytosis. There was no mortality.

PMID- 16799603
TI  - Pediatric mastocytosis.
AB  - The onset of mastocytosis occurs between birth and 2 years of age in
      approximately 55% of all cases; an additional 10% develop the disease before the
      age of 15 years. Mastocytosis in these age groups differs in many respects from
      mastocytosis that has its onset in adulthood. The typical presentation of
      pediatric-onset mastocytosis consists of cutaneous manifestations: either a
      solitary mastocytoma, urticaria pigmentosa, or, less commonly, diffuse cutaneous
      mastocytosis. Particularly in infants, bullous eruptions may occur. Mastocytosis
      in infants and children may involve internal organs, including the bone marrow
      and the gastrointestinal tract, although such manifestations appear to be less
      common in children than in adults. Plasma histamine levels may be elevated in
      pediatric-onset mastocytosis. Treatment usually involves the use of H1 and H2
      antihistamines to control itching and to control the hypersecretion of gastric
      acid that may occur. The prognosis for children with mast cell disease is
      variable; approximately half of the children with urticaria pigmentosa may
      experience resolution of lesions and symptoms by adolescence.

PMID- 16799604
TI  - Biochemical diagnosis of systemic mast cell disorders.
AB  - Systemic mastocytosis is characterized by an abnormal proliferation of tissue
      mast cells. Symptoms of mastocytosis are primarily attributed to the release of
      mast cell mediators during episodes of systemic activation of the excessive
      numbers of mast cells. Thus, biochemical evidence for the release of increased
      quantities of mast cell secretory products can suggest or confirm, depending on
      the clinical situation, a diagnosis of systemic mastocytosis. A major advantage
      of the biochemical approach to the diagnosis of systemic mast cell disease is
      that it has allowed the recognition of a class of patients in whom episodes of
      systemic mastocyte activation can be unequivocally documented biochemically but
      in whom clear-cut evidence of abnormal mast cell proliferation is lacking by
      current histologic criteria. Although the release of increased quantities of mast
      cell mediators can be demonstrated during episodes of mast cell activation in
      such patients, mediator levels are usually normal at quiescent times. By
      contrast, patients with proliferative mast cell disease (mastocytosis) usually
      exhibit chronic overproduction of mast cell mediators. Mast cell secretory
      products that can be measured in an attempt to obtain biochemical evidence of
      systemic mast cell activation include histamine, prostaglandin D2, tryptase, and
      heparin. The analytical approaches to assessing release of those individual mast
      cell products are evaluated. In general, the diagnosis and investigation of
      patients with systemic mast cell activation can best be accomplished by concerted
      use of histologic examination of key tissues together with analysis of chemical
      markers of the mast cell.

PMID- 16799606
TI  - The skin in mastocytosis.
AB  - The most frequent site of organ involvement in patients with any form of
      mastocytosis is the skin. Cutaneous expressions include urticaria pigmentosa,
      mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia
      macularis eruptiva perstans. The cutaneous lesions tend to appear early in life.
      Although urticaria pigmentosa has been reported in 12 pairs of twins and one set
      of triplets, the majority of affected individuals have no familial association.
      Most patients with systemic mastocytosis have skin lesions; however, an
      occasional patient will have systemic disease with no other skin features than
      flushing. In lesional cutaneous sites and in non-lesional skin, there is an
      increase in the number of mast cells. Electron microscopy shows quantitative
      differences between lesional skin mast cells from patients with and without
      systemic disease. The mast cells from adult patients with systemic disease have a
      larger mean cytoplasmic area, nuclear size, and granule diameter. The granules
      contain predominantly grating/lattice structures. The cutaneous mast cells
      contain tryptase and chymase. They retain their functional reactivities to
      relevant secretory stimuli, such as C3a, morphine sulfate, and calcium ionophore
      A23187. Lesional skin contains histamine, leukotriene B4, prostaglandin D2, 5
      hydroxyeicosatetraenoic acid, platelet-activating factor, and heparin. Treatment
      of the cutaneous manifestations includes the use of H1 and H2 antihistamines,
      oral disodium cromoglycate, psoralens plus ultraviolet A photochemotherapy, and
      potent topical corticosteroid preparations.

PMID- 16799605
TI  - Ultrastructural and immunohistochemical characterization of normal mast cells at
      multiple body sites.
AB  - This article reviews the ultrastructural and immunohistochemical features of
      normal human mast cells (MC) at multiple tissue sites. Current literature
      indicates that granules containing discrete scrolls (scroll-rich morphology) are
      frequent in MC from bowel mucosa and lung, locations where the majority of MC
      show only tryptase immunoreactivity (MC(T)). In contrast, most MC from skin,
      breast parenchyma, axillary lymph nodes, and bowel submucosa are characterized by
      scroll-poor morphology (that is, granules are rimmed by incomplete scrolls
      forming parallel lamellae and containing central, amorphous granular material or
      grating/lattice-like structures) and show both tryptase and chymase
      immunoreactivity (MC(TC)). MC having granules with both scroll-rich and scroll
      poor features can occur in all tissue sites, and an occasional MC, especially in
      lung and bowel, may show only chymase immunoreactivity (MC(C)). Chymase
      immunoreactivity in MC also is closely associated with avidin binding and
      carboxypeptidase reactivity. We conclude that there is ultrastructural and
      immunophenotypic diversity among normal human MC, although certain forms
      predominate in specific tissue environments. In skin, breast tissue, axillary
      lymph nodes, and bowel submucosa MC tend to have scroll-poor granules and stain
      for avidin, chymase, tryptase, and carboxypeptidase, whereas, in lung and bowel
      mucosa MC granules tend to be scroll-rich and stain only for tryptase with
      currently available reagents.

PMID- 16799607
TI  - The role of the mast cell in clinical gastrointestinal disease with special
      reference to systemic mastocytosis.
AB  - The gastrointestinal tract is a rich source of mast cells with an enormous
      surface area that permits a high degree of interaction between the mast cell and
      intestinal luminal contents. The active metabolic products of the mast cell
      influence gastrointestinal secretion, absorption, and motility through paracrine
      effects of local mast cell degranulation and also cause systemic effects through
      the release of cellular products into the blood stream. Systemic mastocytosis
      influences physiologic function through the systemic effects of mast cell
      products released from focal (e.g., bone marrow) or wide spread increases in mast
      cell number. Local gastrointestinal proliferation of mast cells in response to
      recognized (e.g., gluten in celiac sprue) or obscure stimuli can alter
      gastrointestinal function and induce systemic symptoms. Celiac sprue,
      inflammatory bowel disease, and non-ulcer dyspepsia are three examples of
      gastrointestinal diseases in which mast cells can be implicated in the
      pathophysiology of the symptoms.

PMID- 16799608
TI  - The liver, spleen, and lymph nodes in mastocytosis.
AB  - In systemic mastocytosis the liver, spleen, and lymph nodes may be infiltrated by
      mast cells, with patterns of infiltration specific for each tissue. This may
      result in hepatosplenomegaly and enlarged lymph nodes. Extensive involvement with
      mast cells may also be associated with organ dysfunction. Specifically, in the
      case of liver, mast cell infiltration may result in fibrosis, portal
      hypertension, and abdominal ascites. Clinically significant involvement of the
      liver, spleen, and lymph nodes appears to be more common in patients with
      aggressive forms of mastocytosis, including those with a hematologic disorder.

PMID- 16799609
TI  - Hematologic aspects of mastocytosis: I: Bone marrow pathology in adult and
      pediatric systemic mast cell disease.
AB  - The typical bone marrow lesions seen in adults with systemic mast cell disease
      (SMCD) are foci of spindle-shaped mast cells in a fibrotic matrix and are found
      in up to 90% of adults with SMCD. Lymphocytes and eosinophils frequently are
      admixed with the mast cells, forming the classic MEL lesion. The mast cell
      lesions can be found in perivascular, peritrabecular, or intertrabecular
      locations and may on occasion completely replace intratrabecular regions of the
      marrow. In contrast, the mast cell lesions found in children with cutaneous mast
      cell disorders are uniformly small and subtle and are most frequently located
      perivascularly. Lymphocytes, eosinophils, and early myeloid elements may be
      associated with these lesions. Of perhaps greater specificity for SMCD is the
      finding of confluent clusters of mast cells on the marrow aspirates; such
      clusters are noted in up to 30% of patients with SMCD.

PMID- 16799610
TI  - Hematologic aspects of mastocytosis: II: Management of hematologic disorders in
      association with systemic mast cell disease.
AB  - Individuals with systemic mast cell disease (SMCD) may develop various
      hematologic abnormalities, including cytopenias, myeloproliferative or
      myelodysplastic syndromes, lymphoproliferative syndromes, and primary or
      secondary leukemias. Management of those patients is often complicated by their
      associated hematologic abnormalities. In the case of non-malignant hematologic
      syndromes, the approach to management is supportive. At present, overt
      malignancies are managed with traditional chemotherapy. The presence of leukemia
      in patients with mast cell disease usually indicates a grave prognosis.

PMID- 16799611
TI  - The treatment of mastocytosis: an overview.
AB  - The treatment of mastocytosis requires a recognition of specific disease patterns
      of involvement, with consequent institution of appropriate therapy based on the
      disease pattern manifested in a given patient. Treatment for most forms of
      mastocytosis is conservative and symptomatic. H1 and H2 antihistamines in
      combination or alone remain the primary drugs of choice. In specific cases,
      patients may require aspirin and/or steroids; some must be prepared to self
      administer epinephrine for severe anaphylactic episodes. In patients with
      associated hematologic disorders, the treatment of the disorder will depend on
      the hematologic findings. In rare cases, and in aggressive forms of mastocytosis
      only, it may be necessary to consider limited forms of chemotherapy.

PMID- 16799614
TI  - Allogeneic hematopoietic stem cell transplantation after rituximab-containing
      myeloablative preparative regimen for acute lymphoblastic leukemia.
AB  - We explored the safety and efficacy of rituximab administered in combination with
      the standard transplant conditioning regimen of cyclophosphamide (Cy) 120 mg/kg
      and total body irradiation (TBI) 12 Gy for adult patients with acute
      lymphoblastic leukemia (ALL). Patients were eligible if their disease expressed
      CD20. Rituximab was administered at 375 mg/m2 weekly for four doses beginning on
      day -7 of the conditioning regimen. Graft-versus-host-disease (GVHD) prophylaxis
      consisted of tacrolimus and methotrexate. Thirty-five patients undergoing matched
      sibling (n = 23) or unrelated donor (n = 12) transplantation were studied, with a
      median age of 30 years (range 15-55 years). At 2 years, progression-free
      survival, treatment-related mortality, and overall survival were 30, 24, and 47%,
      respectively. There was no delay in engraftment or increased incidence of
      infection. The cumulative incidence of grade II-IV acute GVHD was 17%, and
      limited and extensive chronic GVHD was 43% at 2 years. The addition of rituximab
      to the standard Cy/TBI transplant conditioning regimen in ALL was safe and well
      tolerated, and there was a suggestion of decreased incidence of acute GVHD when
      compared to historically reported GVHD rates for this group of patients.

PMID- 16799617
TI  - Southern Europe as an example of interaction between various environmental
      factors: a systematic review of the epidemiologic evidence.
AB  - Hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol consumption are
      major causes of hepatocellular carcinoma (HCC) worldwide. We performed a
      systematic review of epidemiologic studies carried out on HCC aetiology in
      Southern Europe, an area with an intermediate-high prevalence of these agents as
      well as of putative risk factors such as tobacco smoking, diabetes and obesity.
      To retrieve the articles, we performed a Medline search for titles and abstracts
      of articles. After the Medline search, we reviewed the papers and reference lists
      to identify additional articles. A synergism between HCV infection and HBV
      infection, overt (hepatitis B virus antigen (HbsAg) positivity) or occult (HBsAg
      negativity with presence of HBV DNA in liver or serum), is suggested by the
      results of some studies. The pattern of the risk for HCC due to alcohol intake
      shows a continuous dose-effect curve without a definite threshold, although most
      studies found that HCC risk increased only for alcohol consumption above 40-60 g
      of ethanol per day. Some evidence supports a positive interaction of alcohol
      intake probably with HCV infection and possibly with HBV infection. A few studies
      found that coffee has a protective effect on HCC risk due to various risk
      factors. Some data also support a role of tobacco smoking, diabetes and obesity
      as single agents or preferably co-factors in causing HCC. In countries with a
      relatively high alcohol consumption and intermediate levels of HCV and HBV
      infections (1-3% of population infected by each virus), such as Mediterranean
      countries, the three main risk factors together account for about 85% of the
      total HCC cases, leaving little space to other known risk factors, such as
      haemochromatosis, and to new, still unrecognised, factors as independent causes
      of HCC.

PMID- 16799618
TI  - Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and
      hepatitis C endemicity.
AB  - Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide.
      It evolves from several chronic liver diseases, most of which culminate in
      cirrhosis. As the most common causes, other than alcoholic cirrhosis, are chronic
      hepatitis B and C infections, its prevalence worldwide is linked to the
      prevalence of these two viruses. Thus, the highest rates are in southeast Asia
      and sub-Saharan Africa, the world's most populous nations, where hepatitis B
      virus infection is endemic. In most western countries, hepatitis C virus
      infection is the predominant cause, and hepatitis B-related liver cancer occurs
      largely among immigrants from countries of high hepatitis B endemicity. In most
      western countries, the incidence and mortality from HCC is increasing as a
      consequence of the chronic sequelae of the 'epidemic' of hepatitis C of the 1960
      1980s. In the US, modeling of this infection predicts a continued rise in liver
      cancer over the next decade. Surveillance by the National Cancer Institute and
      the Centers for Disease Control confirms the increasing incidence of and
      mortality from HCC to the year 2000, although subsequent analyses suggest a
      slowing or possibly decline in the rate of increase. Whether this trend will
      continue requires further evaluation.

PMID- 16799619
TI  - Genetics of hepatocellular tumors.
AB  - Numerous genetic alterations are accumulated during the process of
      hepatocarcinogenesis. These genetic alterations can be divided into two groups.
      The first set of genetic alterations is specific of hepatocellular tumor risk
      factors. It includes integration of hepatitis B virus (HBV) DNA, R249S TP53
      (tumor protein p53) mutation in aflatoxin B1-exposed patients, KRAS mutations
      related to vinyl chloride exposure, hepatocyte nuclear factor 1alpha (HNF1alpha)
      mutations associated to hepatocellular adenomas and adenomatosis polyposis coli
      (APC) germline mutations predisposing to hepatoblastomas. The second set of
      genetic alterations are etiological nonspecific, it includes recurrent gains and
      losses of chromosomes, alteration of TP53 gene, activation of WNT/beta-catenin
      pathway through CTNNB1/beta-catenin and AXIN (axis inhibition protein) mutations,
      inactivation of retinoblastoma and IGF2R (insulin-like growth factor 2 receptor)
      pathways through inactivation of RB1 (retinoblastoma 1), P16 and IGF2R.
      Comprehensive analyses of these genetic alterations have defined two pathways of
      hepatocarcinogenesis according to the presence or the absence of chromosomal
      instability. Hepatitis B virus and poorly differentiated tumors are related to
      chromosome instable tumors associated with frequent TP53 mutations, whereas non
      HBV and well-differentiated tumors are related to chromosomal stable samples that
      are frequently beta-catenin activated. These classifications have clinical
      relevance as genetic alterations may also be related to prognosis.

PMID- 16799620
TI  - Dysregulation of growth factor signaling in human hepatocellular carcinoma.
AB  - Dysregulation of pleiotropic growth factors, receptors and their downstream
      signaling pathway components represent a central protumorigenic principle in
      human hepatocarcinogenesis. Especially the Insulin-like Growth Factor/IGF-1
      receptor (IGF/IGF-1R), Hepatocyte Growth Factor (HGF/MET), Wingless (Wnt/beta
      catenin/FZD), Transforming Growth Factor alpha/Epidermal Growth Factor receptor
      (TGFalpha/EGFR) and Transforming Growth Factor beta (TGFbeta/TbetaR) pathways
      contribute to proliferation, antiapoptosis and invasive behavior of tumor cells.
      This review focuses on the relevant alterations in these pathways identified in
      human human hepatocellular carcinomas (HCCs). Resultant functional effects are
      modulated by multiple cross-talks between the different signaling pathways and
      additional tumor-relevant factors, such as cyclooxygenase-2 and p53. Several
      specific strategies are currently under development such as receptor kinase
      inhibitors, neutralizing antibodies and antagonistic proteins, which may improve
      the systemic treatment of human HCCs.

PMID- 16799621
TI  - Comparative and integrative functional genomics of HCC.
AB  - Global gene expression profiling of hepatocellular carcinoma (HCC) is a promising
      new technology that has already refined the diagnosis and prognostic predictions
      of HCC patients. This has been accomplished by identifying genes whose expression
      pattern is associated with clinicopathological features of HCC tumors. Molecular
      characterization of HCC from gene expression profiling studies will undoubtedly
      improve the prediction of treatment responses, selection of treatments for
      specific molecular subtypes of HCC and ultimately the clinical outcome of HCC
      patients. The research focus is now shifting toward the identification of genetic
      determinants that are components of the specific regulatory pathways altered in
      cancers, and that may constitute novel therapeutic targets. Here we review the
      recent advances in gene expression profiling of HCC and discuss the future
      strategies for analysing large and complicated data sets from microarray studies
      and how to integrate these with diverse genomic data.

PMID- 16799622
TI  - Proteomics for the early detection and treatment of hepatocellular carcinoma.
AB  - The prognosis for hepatocellular carcinoma (HCC) is poor and has not improved in
      recent years, largely owing to lack of early diagnosis, frequent recurrence after
      surgery and resistance to chemotherapy. Proteomics holds the promise of improving
      our understanding of HCC carcinogenesis and progression as well as of discovering
      novel diagnostics and therapeutics. Proteomic analyses of HCC cell lines, animal
      models and serum and tumor tissue from patients with HCC have been performed to
      date. Proteomic technologies have greatly improved in the past few years as
      reviewed here. It is anticipated that with the recent development of protein
      tagging, protein separation methods and mass spectrometry sensitivity, proteomic
      studies of HCC will allow the identification of diagnostic and prognostic
      biomarkers as well as therapeutic targets, which could greatly improve the
      clinical management of HCC patients.

PMID- 16799623
TI  - Liver stem cells and their implication in hepatocellular and cholangiocarcinoma.
AB  - In the liver, several cell types have the longevity that is needed to be the cell
      of origin of a cancer: hepatocytes, cholangiocytes and progenitor cells. The
      latter are located in the most peripheral branches of the biliary tree, the
      ductules and canals of Hering. The most important risk factors for liver cancer
      are chronic viral hepatitis B and C and alcoholic and non-alcoholic
      steatohepatitis. In these and other chronic liver diseases, progenitor cell
      activation is seen, rendering them a target cell population for carcinogenesis.
      The degree of activation is positively correlated with the inflammatory activity
      and the stage of the disease. Recently, it has been shown that in the cirrhotic
      stage of most chronic liver diseases, the hepatocytes become senescent owing to
      telomere shortening. This makes it even more plausible that at least part of the
      hepatocellular carcinomas originate from a progenitor cell. Hepatocellular
      carcinomas expressing progenitor cell/ductular markers like cytokeratin 19 have a
      more aggressive clinical course. It is therefore important to recognize this
      entity.

PMID- 16799624
TI  - Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related
      human carcinogenesis.
AB  - As discussed in detail in other chapters of this review, chronic hepatitis B
      (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most
      HCCs complicate the evolution of an active or inactive cirrhosis. However, some
      tumors occur on livers with minimal histological changes; the prevalence of such
      cases varies from one geographical region to the other, being much higher in the
      southern half of Africa (around 40% of HCCs) than in Asia, America and Europe,
      where at least 90% of HCCs are associated with the cirrhosis. This heterogeneity
      is probably a reflection of different environmental and genetic factors. This
      review will summarize the current knowledge on the mechanisms involved in HBV
      related liver carcinogenesis. It will show in particular how viruses can be
      viewed as tools to discover and dissect new cellular pathways involved in cancer
      development and emphasize the potential synergistic effects between HBV and
      hepatitis C virus, as well as between viral infections and other environmental
      factors, such as alcohol.

PMID- 16799625
TI  - Viral hepatitis and liver cancer: the case of hepatitis C.
AB  - Chronic infection with the hepatitis C virus (HCV) is a major risk factor for the
      development of hepatocellular carcinoma (HCC) worldwide. The pathogenesis of HCC
      in HCV infection has extensively been analysed. Hepatitis C virus-induced chronic
      inflammation and the effects of cytokines in the development of fibrosis and
      liver cell proliferation are considered as one of the major pathogenic
      mechanisms. Increasing experimental evidence suggests that HCV contributes to HCC
      by directly modulating pathways that promote the malignant transformation of
      hepatocytes. Hepatitis C virus is an RNA virus that does not integrate into the
      host genome but HCV proteins interact with many host-cell factors well beyond
      their roles in the viral life cycle and are involved in a wide range of
      activities, including cell signaling, transcription, cell proliferation,
      apoptosis, membrane rearrangements, vesicular trafficking and translational
      regulation. At least four of the HCV gene products, namely HCV core, NS3, NS4B
      and NS5A, have been shown to exhibit transformation potential in tissue culture
      and several potentially oncogenic pathways have been shown to be altered by the
      expression of HCV proteins. Both HCV core and NS5A induce the accumulation of
      wild-type beta-catenin and the Wnt-beta-catenin pathway emerges as a common
      target for HCV (and HBV) in human HCCs, also independently from axin/beta-catenin
      gene mutations. Induction of both endoplasmic reticulum stress and oxidative
      stress by HCV proteins might also contribute to HCV transformation. Most of the
      putative transforming functions of the HCV proteins have been defined in
      artificial cellular systems, which may not be applicable to HCV infection in
      vivo, and still need to be established in relevant infection and disease models.

PMID- 16799626
TI  - New aspects of diagnosis and therapy of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is one of the major cancer killers. It affects patients
      with chronic liver disease who have established cirrhosis, and currently is the
      most frequent cause of death in these patients. The main risk factors for its
      development are hepatitis B and C virus infection, alcoholism and aflatoxin
      intake. If acquistion of risk factors is not prevented and cirrhosis is
      established, the sole option to improve survival is to detect the tumor at an
      early stage when effective therapy may be indicated. Early detection plans should
      be based on hepatic ultrasonography every 6 months, whereas determination of
      tumor markers is not efficient. Upon detection of a hepatic nodule, there is a
      need to establish unequivocal diagnosis, either through biopsy or through the
      application of non-invasive criteria based on the specific radiology appearance
      of the tumor: fast arterial uptake of contrast followed by venous washout.
      Effective treatment for liver cancer includes surgical resection, liver
      transplantation and percutaneous ablation. These options provide a high rate of
      complete responses and are assumed to improve survival that should exceed 50% at
      5 years. If the tumor is diagnosed at an advanced stage, the sole option that
      improves survival is transarterial chemoembolization. Ongoing research should
      further advance the time at diagnosis and identify new and effective options
      targeting molecular pathways governing tumor progression.

PMID- 16799627
TI  - RNA interference-mediated prevention and therapy for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related
      death and is on the increase worldwide. Hepatocellular carcinoma results from
      chronic liver disease and cirrhosis most commonly associated with chronic
      hepatitis B (HBV) or hepatitis C (HCV) infection. The highest incidences of HCC
      are found in China and Africa, where chronic HBV infection is the major risk
      component. In the United States, Europe and Japan, the significant increase in
      HCC and HCC-related deaths within the last three decades is mainly attributed to
      the rise in the number of HCV-infected individuals; smaller increases of HCC are
      associated with HBV. Given that HCV and HBV infection account for the majority of
      HCCs, therapeutic and prophylactic approaches to control or eliminate virus
      infection may prove effective in reducing the occurrence of HCC. Although anti
      viral therapies exist for both HBV and HCV infections, they are ineffective for a
      significant number of patients. In addition, some treatments such as interferon
      therapy are dose limiting owing to toxic side effects. Clearly, new approaches
      are needed. RNA interference (RNAi)-based approaches may meet this need and have
      already shown promising preclinical results in cell culture and animal models.
      Although this paper focuses on the potential of RNAi as a prophylactic for HCC
      development, the potential use of RNAi-mediated approaches for HCC therapy will
      also be discussed.

PMID- 16799628
TI  - New therapies for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is
      often diagnosed at an advanced stage when most potentially curative therapies
      such as resection, transplantation or percutaneous and transarterial
      interventions are of limited efficacy. The fact that HCC is resistant to
      conventional chemotherapy, and is rarely amenable to radiotherapy, leaves this
      disease with no effective therapeutic options and a very poor prognosis.
      Therefore, the development of more effective therapeutic tools and strategies is
      much needed. HCCs are phenotypically and genetically heterogeneous tumors that
      commonly emerge on a background of chronic liver disease. However, in spite of
      this heterogeneity recent insights into the biology of HCC suggest that certain
      signaling pathways and molecular alterations are likely to play essential roles
      in HCC development by promoting cell growth and survival. The identification of
      such mechanisms may open new avenues for the prevention and treatment of HCC
      through the development of targeted therapies. In this review we will describe
      the new potential therapeutic targets and clinical developments that have emerged
      from progress in the knowledge of HCC biology, In addition, recent advances in
      gene therapy and combined cell and gene therapy, together with new radiotherapy
      techniques and immunotherapy in patients with HCC will be discussed.

PMID- 16799629
TI  - Differential regulation of tumor necrosis factor-alpha-converting enzyme and
      angiotensin-converting enzyme by type I and II interferons in human normal and
      leukemic myeloid cells.
AB  - The transmembrane metalloproteases angiotensin-converting enzyme (ACE) and tumor
      necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE/ADAM-17) have been
      associated with inflammation, cancer progression and angiogenesis. Few
      investigations into the regulation of these enzymes by physiological stimuli have
      been reported. In this study, we investigated the influence of interferons (IFNs)
      type I (alpha, beta) and II (gamma) on ACE and TACE expression of human leukemic
      NB4 cells and monocytes. We assessed the expression of proteases by reverse
      transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay and
      immunofluorescence analyses. IFNgamma, but not type I IFNs, upregulated membrane
      ACE in a dose- and time-dependency and this was reflected by the increase of ACE
      enzymatic activity and ACE mRNA. ACE upregulation was dependent on protein
      synthesis. Treatment of the interferon responsive factor 1 (IRF1)-unresponsive
      HepG2 cell line with IFNgamma did not affect ACE expression, thus suggesting the
      participation of the IRF1 signaling pathway in IFNgamma-mediated ACE upregulation
      in myeloid cells. In contrast, both types of IFNs, in a dose- and time-dependent
      manner, downregulated surface TACE without affecting TACE transcript. Soluble
      TACE was not detected in the medium of IFN-treated cells. IFNgamma-mediated
      decrease of surface TACE in NB4 cells was reversible, and correlated with an
      increase in intracellular TACE, suggesting that cell surface TACE was
      internalized in response to IFNs. These findings, showing the presence of IFN
      dependent controlled mechanisms by which ACE and TACE levels are regulated in
      human normal and leukemic myeloid cells, may have implications in the context of
      current investigations on the therapeutic potential of IFNs.

PMID- 16799630
TI  - ZNF185, an actin-cytoskeleton-associated growth inhibitory LIM protein in
      prostate cancer.
AB  - We have recently identified ZNF185 as a gene that is downregulated in prostate
      cancer (PCa), in part via epigenetic alteration, and maybe associated with
      disease progression. In this study, we cloned the ZNF185 cDNA from normal human
      prostate tissues and investigated its biological function. We show that ZNF185 is
      a novel actin-cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain
      containing protein that localizes to F-actin structures, and is enriched at focal
      adhesions. We find that the NH(2)-terminal region, which we designate the actin
      targeting domain, facilitates ZNF185 binding to actin in vitro and is both
      necessary and sufficient to mediate actin-cytoskeleton targeting of ZNF185,
      whereas the LIM domain, which is localized in the COOH-terminus is dispensable
      for this phenomenon. Interestingly, ectopic expression of full-length ZNF185, but
      not a mutant lacking the actin-targeting domain, could suppress proliferation and
      anchorage-independent growth of PCa cells. Together, our data suggest that ZNF185
      may function as a tumor-suppressor protein by associating with the actin
      cytoskeleton.

PMID- 16799631
TI  - Identification of a tumor suppressive critical region mapping to 3p14.2 in
      esophageal squamous cell carcinoma and studies of a candidate tumor suppressor
      gene, ADAMTS9.
AB  - A gene critical to esophageal cancer has been identified. Functional studies
      using microcell-mediated chromosome transfer of intact and truncated donor
      chromosomes 3 into an esophageal cancer cell line and nude mouse tumorigenicity
      assays were used to identify a 1.61 Mb tumor suppressive critical region (CR)
      mapping to chromosome 3p14.2. This CR is bounded by D3S1600 and D3S1285
      microsatellite markers. One candidate tumor suppressor gene, ADAMTS9, maps to
      this CR. Further studies showed normal expression levels of this gene in tumor
      suppressed microcell hybrids, levels that were much higher than observed in the
      recipient cells. Complete loss or downregulation of ADAMTS9 gene expression was
      found in 15 out of 16 esophageal carcinoma cell lines. Promoter hypermethylation
      was detected in the cell lines that do not express this gene. Re-expression of
      ADAMTS9 was observed after demethylation drug treatment, confirming that
      hypermethylation is involved in gene downregulation. Downregulation of ADAMTS9
      was also found in 43.5 and 47.6% of primary esophageal tumor tissues from Hong
      Kong and from the high-risk region of Henan, respectively. Thus, this study
      identifies and provides functional evidence for a CR associated with tumor
      suppression on 3p14.2 and provides the first evidence that ADAMTS9, mapping to
      this region, may contribute to esophageal cancer development.

PMID- 16799632
TI  - Cellular stress triggers the human topoisomerase I damage response independently
      of DNA damage in a p53 controlled manner.
AB  - The 'human topoisomerase I (htopoI) damage response' was reported to be triggered
      by various kinds of DNA lesions. Also, a high and persistent level of htopoI
      cleavage complexes correlated with apoptosis. In the present study, we
      demonstrate that DNA damage-independent induction of cell death using colcemid
      and tumor necrosis factor alpha is also accompanied by a strong htopoI response
      that correlates with the onset of apoptotic hallmarks. Consequently, these
      results suggest that htopoI cleavage complex formation may be caused by signaling
      pathways independent of the kind of cellular stress. Thus, protein interactions
      or signaling cascades induced by DNA damage or cellular stress might lead to the
      formation of stabilized cleavage complexes rather than the DNA lesion itself.
      Finally, we show that p53 not only plays a key role in the regulation of the
      htopoI response to UV-C irradiation but also to treatment with colcemid.

PMID- 16799633
TI  - MUC4 expression is regulated by cystic fibrosis transmembrane conductance
      regulator in pancreatic adenocarcinoma cells via transcriptional and post
      translational mechanisms.
AB  - MUC4 mucin is a high molecular weight transmembrane glycoprotein that plays
      important roles in tumour biology. It is aberrantly expressed in pancreatic
      adenocarcinoma, while not being detectable in the normal pancreas. Previous
      studies have demonstrated that the cystic fibrosis transmembrane conductance
      regulator (CFTR), a chloride channel that is defective in CF, is implicated in
      multiple cellular functions, including gene regulation. In the present study,
      using a CFTR-defective pancreatic cancer cell line and its derived subline
      expressing functional CFTR, we report that MUC4 expression is negatively
      regulated by CFTR. Short-interfering RNA (siRNA)-mediated silencing of CFTR also
      leads to an increased expression of MUC4. Additionally, our results suggest that
      CFTR-mediated regulation of MUC4 is cell density-dependent and is achieved by
      transcriptional and posttranslational mechanisms. Moreover, in a panel of
      pancreatic cancer cell lines and normal pancreas, we observed that CFTR was
      downregulated in pancreatic cancer cells and negatively correlated with MUC4 in
      most cases. An aberrant expression of MUC4 was also detected in the CF pancreas.
      Downregulation of CFTR in pancreatic adenocarcinoma and its inverse association
      with the tumour-linked mucin, MUC4, indicate novel function(s) of CFTR in
      pancreatic tumour biology and suggest the implication of new signalling
      pathway(s) in MUC4 regulation.

PMID- 16799634
TI  - 5-Aza-2'-deoxycytidine-mediated reductions in G9A histone methyltransferase and
      histone H3 K9 di-methylation levels are linked to tumor suppressor gene
      reactivation.
AB  - The epigenetic silencing of tumor suppressor genes is a common event during
      carcinogenesis, and often involves aberrant DNA methylation and histone
      modification of gene regulatory regions, resulting in the formation of a
      transcriptionally repressive chromatin state. Two examples include the
      antimetastatic, tumor suppressor genes, desmocollin 3 (DSC3) and MASPIN, which
      are frequently silenced in this manner in human breast cancer. Treatment of the
      breast tumor cell lines MDA-MB-231 and UACC 1179 with 5-aza-2'-deoxycytidine (5
      aza-CdR) induced transcriptional reactivation of both genes in a dose-dependent
      manner. Importantly, DSC3 and MASPIN reactivation was closely and consistently
      linked with significant decreases in promoter H3 K9 di-methylation. Moreover, 5
      aza-CdR treatment also resulted in global decreases in H3 K9 di-methylation, an
      effect that was linked to its ability to mediate dose-dependent, post
      transcriptional decreases in the key enzyme responsible for this epigenetic
      modification, G9A. Finally, small interfering RNA (siRNA)-mediated knockdown of
      G9A and DNMT1 led to increased MASPIN expression in MDA-MB-231 cells, to levels
      that were supra-additive, verifying the importance of these enzymes in
      maintaining multiple layers of epigenetic repression in breast tumor cells. These
      results highlight an additional, complimentary mechanism of action for 5-aza-CdR
      in the reactivation of epigenetically silenced genes, in a manner that is
      independent of its effects on DNA methylation, further supporting an important
      role for H3 K9 methylation in the aberrant repression of tumor suppressor genes
      in human cancer.

PMID- 16799635
TI  - TRAF4 overexpression is a common characteristic of human carcinomas.
AB  - Tumor necrosis factor receptor (TNFR) associated factor 4 (TRAF4) was initially
      identified as a gene amplified and overexpressed in breast carcinomas. Our aim
      was to evaluate whether TRAF4 protein overexpression exists in other cancer
      types. Immunohistochemistry analysis of tumor samples from 623 patients with 20
      different tumor types showed that TRAF4 was overexpressed in 268 tumors (43%),
      including 82 of 137 lung adenocarcinomas (60%). Interestingly, 32 primary tumors
      and their matching metastases exhibited mostly similar TRAF4 expression pattern.
      TRAF4 protein overexpression was limited to cancer cells and the subcellular
      localization was consistently cytoplasmic in a large majority of cases. To
      investigate changes in TRAF4 gene copy number, 125 cases from six different types
      of carcinomas were also analysed by fluorescence in situ hybridization. Out of
      the 28 cases (22%) showing an increased TRAF4 gene copy number, 23 (82%) were
      overexpressing the protein. Thus, TRAF4 gene amplification is one of the
      mechanisms responsible for TRAF4 protein overexpression in human cancers.
      Considering that TRAF4 is located at 17q11.2 in a region of amplification devoid
      of known oncogenes and is commonly overexpressed in cancer, our data support an
      oncogenic role for TRAF4.

PMID- 16799636
TI  - Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by
      histone deacetylation and methylation in colorectal cancer.
AB  - Hypoxia, via the hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2), upregulates
      many genes involved in cell survival. However, proapoptotic pathways are also
      induced. BCL-2/adenovirus E1B-19 kDa-interacting protein 3 (BNIP3) represents a
      paradigm of a cell death protein that is hypoxically upregulated via HIF-1 in
      most cancers. We found that in contrast to many other cell types, 6/8 colorectal
      cancer (CRC) cell lines show little hypoxic induction of BNIP3 despite an intact
      HIF signalling system. Colorectal tumour tissue also loses BNIP3 expression
      relative to matched normal samples. Downregulation of hypoxic BNIP3 in CRC cells
      was independent of the expression of other BCL-2 family members, or BNIP3L. That
      BNIP3 plays a functional role in hypoxic survival in CRC cells was demonstrated
      by the fact that CRC cell lines that do not upregulate BNIP3 or have been treated
      with BNIP3 RNA interference were insensitive to hypoxia-induced cell death.
      Promoter methylation and histone deacetylation were shown to silence BNIP3 in
      these CRC cell lines. Of significance, hypoxic induction of BNIP3 was restored in
      4/6 cell lines by trichostatin-A treatment alone. These data suggest that BNIP3
      plays an important role in hypoxic cell death and epigenetic mechanisms
      selectively silence its expression in CRC.

PMID- 16799637
TI  - Histone deacetylase inhibitors induce the degradation of the t(8;21) fusion
      oncoprotein.
AB  - The t(8;21) chromosomal translocation that generates the fusion oncoprotein RUNX1
      ETO predominates in leukemia patients of the French-American-British (FAB) class
      M2 subtype. The oncoprotein has the capacity to promote expansion of
      hematopoietic stem/progenitor cells and induces leukemia in association with
      other genetic alterations. Here, we show that RUNX1-ETO undergoes degradation in
      response to treatment with histone deacetylase inhibitors, one of which,
      depsipeptide (DEP), is currently undergoing phase II clinical testing in a
      variety of malignancies. These compounds induce turnover of RUNX1-ETO without
      affecting the stability of RUNX1-ETO partner proteins. In addition, RUNX1-ETO
      physically interacts with heat shock protein 90 (HSP90). DEP treatment interrupts
      the association of RUNX1-ETO with HSP90 and induces proteasomal degradation of
      RUNX1-ETO. DEP and the HSP90 antagonist 17-allylamino-geldanamycin (17-AAG) both
      triggered RUNX1-ETO degradation, but without any additive or cooperative effects.
      These findings may stimulate the development of more rational and effective
      approaches for treating t(8;21) patients using histone deacetylase inhibitors or
      HSP90 inhibitors.

PMID- 16799638
TI  - Transcription factors control invasion: AP-1 the first among equals.
AB  - Metastasis, the aggressive spread of a malignant tumor to distant organs, is a
      major cause of death in cancer patients. Despite this critical role in cancer
      outcomes, the molecular mechanisms that control this process are just beginning
      to be understood. Metastasis is largely dependent upon the ability of tumor cells
      to invade the barrier formed by the basement membrane and to migrate through
      neighboring tissues. This review will summarize the evidence that tumor cell
      invasion is the result of oncogene-mediated signal transduction pathways that
      control the expression of a specific set of genes that together mediate tumor
      cell invasion. We focus on the role of the transcription factor AP-1 to both
      induce the expression of genes that function as invasion effectors and repress
      other genes that function as invasion suppressors. This identifies AP-1 as a
      critical regulator of a complex program of gene expression that defines the
      invasive phenotype.

PMID- 16799639
TI  - Progestin-induced caveolin-1 expression mediates breast cancer cell
      proliferation.
AB  - Progestin regulation of gene expression was assessed in the progestin-dependent
      murine tumor line C4HD which requires MPA, a synthetic progestin, for in vivo
      growth and expresses high levels of progesterone receptor (PR). By using
      suppressive subtractive hybridization, caveolin-1 was identified as a gene whose
      expression was increased with in vivo MPA treatment. By Northern and Western blot
      analysis, we further confirmed that caveolin-1 mRNA and protein expression
      increased in MPA-treated tumors as compared with untreated tumors. When primary
      cultures of C4HD cells were treated in vitro with MPA, caveolin-1 levels also
      increased, effect that was abolished by pre-treatment with progestin antagonist
      RU486. In addition, MPA promoted strong caveolin-1 promoter transcriptional
      activation both in mouse and human breast cancer cells. We also showed that MPA
      regulation of caveolin-1 expression involved in activation of two signaling
      pathways: MAPK and PI-3K. Short-term MPA treatment of C4HD cells led to tyrosine
      phosphorylation of caveolin-1 protein, where Src was the kinase involved.
      Additionally, we showed that MPA-induced association of caveolin-1 and PR, which
      was detected by coimmunoprecipitation and by confocal microscopy. Finally, we
      proved that MPA-induced proliferation of C4HD cells was inhibited by suppression
      of caveolin-1 expression with antisense oligodeoxynucleotides to caveolin-1 mRNA.
      Furthermore, we observed that inhibition of caveolin-1 expression abrogated PR
      capacity to induced luciferase activity from a progesterone response element
      driven reporter plasmid. Comprehensively, our results demonstrated for the first
      time that caveolin-1 expression is upregulated by progestin in breast cancer. We
      also demonstrated that caveolin-1 is a downstream effector of MPA that is
      partially responsible for the stimulation of growth of breast cancer cells.

PMID- 16799640
TI  - Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers
      from formalin-fixed paraffin-embedded archival tissues.
AB  - Successful treatment of multiple cancer types requires early detection and
      identification of reliable biomarkers present in specific cancer tissues. To test
      the feasibility of identifying proteins from archival cancer tissues, we have
      developed a methodology, termed direct tissue proteomics (DTP), which can be used
      to identify proteins directly from formalin-fixed paraffin-embedded prostate
      cancer tissue samples. Using minute prostate biopsy sections, we demonstrate the
      identification of 428 prostate-expressed proteins using the shotgun method.
      Because the DTP method is not quantitative, we employed the absolute
      quantification method and demonstrate picogram level quantification of prostate
      specific antigen. In depth bioinformatics analysis of these expressed proteins
      affords the categorization of metabolic pathways that may be important for
      distinct stages of prostate carcinogenesis. Furthermore, we validate Wnt-3 as an
      upregulated protein in cancerous prostate cells by immunohistochemistry. We
      propose that this general strategy provides a roadmap for successful
      identification of critical molecular targets of multiple cancer types.

PMID- 16799641
TI  - Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal
      epithelial cells.
AB  - Detachment of normal epithelial cells from the extracellular matrix triggers
      apoptosis, a phenomenon called anoikis. Conversely, carcinoma cells tend to be
      relatively more anoikis-resistant than their normal counterparts, and this
      increased resistance represents a critical feature of the malignant phenotype.
      Mechanisms that control susceptibility and resistance to anoikis are not fully
      understood. It is now known that detachment of non-malignant epithelial cells
      triggers both pro- and antiapoptotic signals, and it is the balance between these
      signals and the duration of detachment that determine further fate of the cells.
      Detachment-induced antiapoptotic events delay anoikis and if cells reattach
      relatively soon after detachment they survive. Direct regulators of apoptosis
      responsible for this delay of anoikis are unknown. We found that detachment of
      non-malignant intestinal epithelial cells triggers upregulation of inhibitors of
      apoptosis protein (IAP) family, such as X-chromosome-linked inhibitor of
      apoptosis protein and cellular inhibitor of apoptosis-2 (cIAP2). We demonstrated
      that this upregulation requires detachment-dependent activation of the
      transcription factor nuclear factor-kappaB. We further observed that various IAP
      antagonists accelerate anoikis, indicating that upregulation of the IAPs delays
      detachment-triggered apoptosis. We conclude that the IAPs are important
      regulators of the balance between detachment-triggered life and death signals.
      Perhaps, not by coincidence, these proteins are often upregulated in carcinomas,
      tumors composed of cells that tend to be anoikis-resistant.

PMID- 16799642
TI  - Modulation of Wnt3a-mediated nuclear beta-catenin accumulation and activation by
      integrin-linked kinase in mammalian cells.
AB  - The Wnt gene family encodes secreted signaling molecules that play important
      roles in tumorgenesis and embryogenesis. The canonical Wnt signaling pathway
      regulates target gene expression via the stabilization and nuclear translocation
      of the cytoplasmic pool of beta-catenin. The activation of integrin-linked kinase
      (ILK) is also known to regulate the stabilization and subsequent nuclear
      translocation of beta-catenin in several epithelial cell models. We now report
      that molecular and pharmacological inhibition of ILK activity in mammalian cells
      directly modulates Wnt signaling by suppressing the stabilization and nuclear
      translocation of beta-catenin, as well as beta-catenin/Lef-mediated
      transcription. Inhibition of ILK activity, but not phosphatidylinositol-3 kinase
      (PI3K) or MEK activities suppresses nuclear beta-catenin stabilization in cells
      stably expressing Wnt3a as well as in cells exposed to either Wnt3a conditioned
      media or purified Wnt3a. Furthermore, ILK inhibition reverses the Wnt3a-induced
      suppression of beta-catenin phosphorylation that accompanies beta-catenin
      stabilization. In addition, we show that ILK can be identified in a complex with
      Wnt pathway components such as adenomatous polyposis coli and GSK-3. Upon
      treatment of L cells with Wnt3a-CM, glycogen synthase kinase-3 (GSK-3beta)
      becomes highly phosphorylated on Ser 9, which is completely abolished upon
      inhibition of ILK activity. However, acute exposure of L cells to purified Wnt3a
      does not result in the stimulation of GSK-3beta Ser 9 phosphorylation, despite
      beta-catenin stabilization. Together our data demonstrate that ILK activity can
      modulate acute Wnt3a mediated beta-catenin phosphorylation, stabilization and
      nuclear activation in a PI3K-independent manner, as well as the more prolonged
      PI3K-dependent secondary effects of Wnt signaling on GSK-3 phosphorylation.
      Finally, we suggest that a novel small molecule inhibitor of ILK, QLT-0267, may
      be a useful tool in the regulation of pathological Wnt signaling.

PMID- 16799643
TI  - Differential regulation of CXC ligand 1 transcription in melanoma cell lines by
      poly(ADP-ribose) polymerase-1.
AB  - The continuous production of the CXC ligand 1 (CXCL1) chemokine by melanoma cells
      is a major effector of tumor growth. We have previously shown that the
      constitutive expression of this chemokine is dependent upon transcription factors
      nuclear factor-kappa B (NF-kappaB), stimulating protein-1 (SP1), high-mobility
      group-I/Y (HMGI/Y), CAAT displacement protein (CDP) and poly(ADP-ribose)
      polymerase-1 (PARP-1). In this study, we demonstrate for the first time the
      mechanism of transcriptional regulation of CXCL1 through PARP-1 in melanoma
      cells. In its inactive state, PARP-1 binds to the CXCL1 promoter in a sequence
      specific manner and prevents binding of NF-kappaB (p65/p50) to its element.
      However, activation of the PARP-1 enzymatic activity enhances CXCL1 expression,
      owing to the loss of PARP-1 binding to the CXCL1 promoter, accompanied by
      enhanced binding of p65 to the promoter. The delineation of the role of NF-kappaB
      interacting factors in the putative CXCL1 enhanceosome will provide key
      information in developing strategies to block constitutive expression of this and
      other chemokines in cancer and to develop targeted therapy.

PMID- 16799644
TI  - Tamoxifen treatment promotes phosphorylation of the adhesion molecules,
      p130Cas/BCAR1, FAK and Src, via an adhesion-dependent pathway.
AB  - Reports that the adhesion-associated molecule p130Cas/BCAR1 promotes resistance
      to tamoxifen suggested that adhesion-mediated signalling may be altered by
      tamoxifen treatment. We find that p130Cas/BCAR1 phosphorylation is enhanced in
      tamoxifen-treated estrogen receptor (ER)-positive MCF-7 breast cancer cells. The
      effects of estrogen and tamoxifen were assessed independently and in combination,
      and the results demonstrate that tamoxifen antagonizes estrogen regulation of
      p130Cas/BCAR1 phosphorylation. Phosphorylation correlates with tamoxifen ER
      antagonist effects, as phosphorylation effects are replicated by the pure
      antiestrogen ICI 182, 780. Correspondingly, phosphorylation is not changed in ER
      negative cells exposed to tamoxifen. We show that deletion of the p130Cas/BCAR1
      substrate domain substantially reduces tamoxifen-induced phosphorylation of
      p130Cas/BCAR1 and confers enhanced sensitivity to tamoxifen. P130Cas/BCAR1 forms
      a phosphorylation-dependent signalling complex with focal adhesion kinase (FAK)
      and Src kinase that promotes adhesion-mediated cell survival. Therefore, we
      examined the kinetics of p130Cas/BCAR1, Src and FAK phosphorylation over a 14-day
      time course and find sustained phosphorylation of these molecules after 7 days
      exposure to tamoxifen. Inhibition of Src kinase is shown to reduce tamoxifen
      promoted p130Cas/BCAR1 phosphorylation and reduce cell viability. Stimulation of
      the Src/FAK/p130Cas/BCAR1 adhesion signalling pathway in tamoxifen-treated MCF-7
      cells does not cause increased migration; however, there is Src-dependent
      phosphorylation of the cell survival molecule Akt. Correspondingly, Akt
      inhibition reduces cell viability in cells treated with tamoxifen. We propose
      that prolonged activation of adhesion-dependent signalling may confer a survival
      advantage in response to additional cellular insults or alternatively, may poise
      cells to develop a migratory phenotype in response to additional cellular cues.

PMID- 16799646
TI  - Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition and
      apoptosis via a cell cycle-dependent mechanism.
AB  - Apoptosis and epithelial-to-mesenchymal transition (EMT) have been implicated in
      a variety of biological processes, such as embryonic development, fibrosis and
      tumor progression. Transforming growth factor-beta (TGF-beta) can induce
      simultaneously both EMT and apoptotic response of epithelial cells. However, the
      underlying mechanism of these biological events remains not well understood. In
      the present study, we show that TGF-beta1 induces apoptosis and EMT in AML-12
      cells in a cell cycle-related manner, in which apoptosis and EMT took place at
      G2/M and G1/S phases, respectively. TGF-beta1-induced apoptosis was correlated
      with different extent of caspase activation at different cell cycle phases.
      Interestingly, increased phosphorylation of protein kinase D (PKD) can be
      observed in G1/S phase in response to TGF-beta1, and inhibition of PKD by
      inhibitor or by small interference RNA blocked EMT but not apoptosis. Our data
      suggest a previously unrecognized role of cell cycle state in the regulation of
      TGF-beta-induced EMT and apoptosis, and demonstrate that PKD is involved in the
      TGF-beta1-induced EMT.

PMID- 16799645
TI  - Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis.
AB  - Wilms' tumor (WT), one of the most common pediatric solid cancers, arises in the
      developing kidney as a result of genetic and epigenetic changes that lead to the
      abnormal proliferation and differentiation of the metanephric blastema. As
      activation of signal transducers and activators of transcription (STATs) plays an
      important role in the maintenance/growth and differentiation of the metanephric
      blastema, and constitutively activated STATs facilitate neoplastic behaviors of a
      variety of cancers, we hypothesized that dysregulation of STAT signaling may also
      contribute to WT pathogenesis. Accordingly, we evaluated STAT phosphorylation
      patterns in tumors and found that STAT1 was constitutively phosphorylated on
      serine 727 (S727) in 19 of 21 primary WT samples and two WT cell lines. An
      inactivating mutation of S727 to alanine reduced colony formation of WT cells in
      soft agar by more than 80% and induced apoptosis under conditions of growth
      stress. S727-phosphorylated STAT1 provided apoptotic resistance for WT cells via
      upregulation of expression of the heat-shock protein (HSP)27 and antiapoptotic
      protein myeloid cell leukemia (MCL)-1. The kinase responsible for STAT1 S727
      phosphorylation in WT cells was identified based upon the use of selective
      inhibitors as protein kinase CK2, not p38, MAP-kinase kinase (MEK)1/2,
      phosphatidylinositol 3'-kinase, protein kinase C or Ca/calmodulin-dependent
      protein kinase II (CaMKII). The inhibition of CK2 blocked the anchorage
      independent growth of WT cells and induced apoptosis under conditions of growth
      stress. Our findings suggest that serine-phosphorylated STAT1, as a downstream
      target of protein kinase CK2, plays a critical role in the pathogenesis of WT and
      possibly other neoplasms with similar STAT1 phosphorylation patterns.

PMID- 16799647
TI  - Na+ -K+ -2Cl- cotransporter is implicated in gender differences in the response
      of the rat aorta to phenylephrine.
AB  - Inhibition of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) with bumetanide reduced
      contractile responses to phenylephrine (PE) in male rat aortas (129+/-4% of 60 mM
      KCl-induced contraction control vs 108+/-7% bumetanide; PE 10(-5) M; P<0.01) but
      did not change equivalent responses in female rat aortas. Removal of the
      endothelium blunted the effect of NKCC1 inhibition on the response to PE (10(-5)
      M) in males, whereas in denuded aorta from female rats, bumetanide reduced this
      response (162+/-5% control vs 146+/-3% bumetanide; P<0.05). NKCC1 basal activity
      did not show gender differences in intact aortic rings, but in the presence of
      PE, bumetanide-sensitive (86)Rb(+)/K(+) uptake increased more in male than female
      aortas (179+/-8 in males vs 158+/-5 nmol (86)Rb(+)/K(+) min(-1) (g aorta)(-1) in
      females; P<0.05). PE did not stimulate NKCC1 activity in denuded aorta from male
      rats. However, in female rats, PE increased NKCC1 activity similarly in both
      denuded (169+/-11 nmol (86)Rb(+)/K(+) min(-1) (g aorta)(-1)) and intact aortas.
      Ovariectomy increased the bumetanide-sensitive (86)Rb(+)/K(+) uptake increase
      elicited by PE (223+/-17 nmol (86)Rb(+)/K(+) min(-1) (g aorta)(-1)) and hormone
      replacement with 17beta-estradiol prevented this effect (159+/-29 nmol
      (86)Rb(+)/K(+) min(-1) (g aorta)(-1)). Na(+),K(+)-ATPase basal activity, measured
      as ouabain-sensitive (86)Rb(+)/K(+) uptake, was similar in male and female rats,
      but the effect of PE was significantly less in intact male aortas (232+/-16 in
      males vs 296+/-25 nmol (86)Rb(+)/K(+) min(-1) (g aorta)(-1) in females; P<0.05).
      Our results suggest that PE induced activation of NKCC1 and Na(+),K(+)-ATPase in
      the rat aorta in a gender-dependent way.

PMID- 16799648
TI  - Activation of lumbosacral 5-HT2C receptors induces bursts of rhythmic activity in
      sympathetic nerves to the vas deferens in male rats.
AB  - 1. We previously demonstrated that p-chloroamphetamine (PCA) intravenously (i.v.)
      evokes a specific patterned bursting response in the vas deferens nerve (VDN) of
      anaesthetised male rats that is associated with contraction of the vas deferens,
      and ejaculation and contraction of the bulbospongiosus muscles. The present study
      used selective 5-HT agonists to induce similar rhythmic bursting responses in the
      VDN in order to reveal the 5-HT receptor subtypes involved. 2. The 5-HT(2C)
      receptor agonist (1.0 mg kg(-1) Ro600175 i.v.) evoked the characteristic bursting
      pattern responses in the VDN. The 5-HT(1A) receptor agonist (1.0 mg kg(-1) 8-OH
      DPAT i.v.) failed to elicit any responses. However, 8-OH-DPAT coadministered in
      combination with Ro600175 induced a potentiation of the responses. 3. Responses
      were also evoked in rats with a mid-thoracic spinalisation, with a more
      predictable response being observed following the combination of agonists. This
      suggests an action of both agonists in the lumbosacral spinal cord. 4. Responses
      were blocked by 0.5 mg kg(-1) SB206553 i.v. (5-HT(2B/C) receptor antagonist) or
      0.5 mg kg(-1) WAY100635 i.v. (5-HT(1A) receptor antagonist), but not 0.1 or 1.0
      mg kg(-1) SB269970 i.v. (5-HT(7) receptor antagonist). 5. We suggest that
      activation of 5-HT(2C) and 5-HT(1A) receptor subtypes synergistically elicits
      contraction of the vas deferens through the activation of sympathetic
      preganglionic neurones in the spinal cord. 6. These data support the idea of a
      proejaculatory action of 5-HT(2C) receptors in the lumbosacral spinal cord,
      suggesting a descending 5-HT excitatory pathway in addition to a 5-HT inhibitory
      pathway. An excitatory action of 8-OH-DPAT at lumbosacral sites is also evident.

PMID- 16799649
TI  - H-89 inhibits transient outward and inward rectifier potassium currents in
      isolated rat ventricular myocytes.
AB  - 1. Voltage clamp was used to investigate the effects of N-[2-p-bromo
      cinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a potent inhibitor of PKA,
      on transient outward K(+) current (I(to)) and inward rectifying K(+) current
      (I(K1)) in rat cardiac muscle. 2. Initial experiments, performed using descending
      voltage ramps, showed that H-89 inhibited both the outward and inward ramp
      currents in a concentration-dependent manner at concentrations between 5 and 60
      micromol l(-1). A similar degree of inhibition was observed when I(to) and I(K1)
      were recorded using square wave depolarising and hyperpolarising voltage steps,
      respectively. 3. The IC(50) was 35.8 micromol l(-1) for I(to) and 27.8 micromol
      l(-1) for I(K1) compared to 5.4 micromol l(-1) for L-type Ca(2+) current (I(Ca)).
      The Hill coefficients for I(to), I(K1) and I(Ca) were -1.97, -1.60 and -1.21,
      respectively. In addition to inhibiting I(to) amplitude, H-89 also accelerated
      the time to peak and the rate of voltage-dependent inactivation so that the time
      course of I(to) was abbreviated. 4. Paired-pulse protocols were performed to
      study the effects of H-89 on steady-state activation and inactivation as well as
      recovery from voltage-dependent inactivation. H-89 produced a concentration
      dependent rightward shift in voltage-dependent activation but had no significant
      effect on steady-state inactivation. Recovery from voltage-dependent inactivation
      was delayed, although this was only visible at the highest concentration (60
      micromol l(-1)) used. In experiments investigating the effects of elevated cyclic
      AMP, the beta-adrenergic agonist isoprenaline and the phosphatase inhibitor
      calyculin A had no major effects on I(to) or I(K1). 6. Data suggest that the
      effects of H-89 on K(+) currents are more complex than simple inhibition of PKA
      mediated phosphorylation.

PMID- 16799650
TI  - The role of constitutive PKA-mediated phosphorylation in the regulation of basal
      I(Ca) in isolated rat cardiac myocytes.
AB  - 1. Pharmacological inhibitors of protein kinase A (PKA) and protein phosphatases
      1/2A were used to determine whether basal L-type Ca(2+) current (I(Ca)) observed
      in the absence of exogenous beta-adrenergic receptor stimulation is sustained by
      PKA-mediated phosphorylation. Amphotericin B was used to record whole-cell I(Ca)
      in the perforated patch-clamp configuration. 2. Calyculin A and isoprenaline
      (both 1 micromol l(-1)) increased basal I(Ca) (P<0.05), whereas H-89 inhibited
      I(Ca) in a concentration-dependent manner with an IC(50) approximately 5 micromol
      l(-1). H-89 also inhibited the response to 1.0 micromol l(-1) isoprenaline,
      although relatively high concentrations (30 micromol l(-1)) were required to
      achieve complete suppression of the response. 3. Double-pulse protocols were used
      to study the effects of 10 micromol l(-1) H-89 on time-dependent recovery of
      I(Ca) from voltage-dependent inactivation as well as the steady-state gating of
      I(Ca). T(0.5) (time for I(Ca) to recover to 50% of the preinactivation amplitude)
      increased in the presence of H-89 (P<0.05) but was unaffected by calyculin A or
      isoprenaline. 4. Steady-state activation/inactivation properties of I(Ca) were
      unaffected by 10 micromol l(-1) H-89 or 1 micromol l(-1) calyculin A, whereas
      isoprenaline caused a leftward shift in both curves so that V(0.5) for activation
      and inactivation became more negative. 5. Data show that basal I(Ca) is regulated
      by cAMP-PKA-mediated phosphorylation in the absence of externally applied beta
      receptor agonists and that relatively high concentrations of H-89 are required to
      fully suppress the response to beta-adrenergic receptor stimulation, thereby
      limiting the value of H-89 as a useful tool in dissecting signalling pathways in
      intact myocytes.

PMID- 16799651
TI  - The use of tensor fascia lata pedicled flap in reconstructing full thickness
      abdominal wall defects and groin defects following tumor ablation.
AB  - BACKGROUND: The tensor fascia lata is a versatile flap with many uses in
      reconstructive plastic surgery. As a pedicled flap its reach to the lower abdomen
      and groin made it an attractive option for reconstructing soft tissue defects
      after tumor ablation. However, debate exists on the safe dimension of the flap,
      as distal tip necrosis is common. Also, the adequacy of the fascia lata as a sole
      substitute for abdominal wall muscles has been disputable. The aim of the current
      study is to report our experience and clinical observations with this flap in
      reconstructing those challenging defects and to discuss the possible options to
      minimize the latter disputable issues. PATIENTS AND METHODS: From April 2001 to
      April 2004, 12 pedicled TFL flaps were used to reconstruct 5 central abdominal
      wall full thickness defects and 6 groin soft tissue defects following tumor
      resection. In one case, bilateral flaps were used to reconstruct a large central
      abdominal wall defect. There were 4 males and 7 females. Their age ranged from 19
      to 60. From the abdominal wall defects group, all repairs were enforced primarily
      with a prolene mesh except for one patient who was the first in this study.
      Patients presenting with groin defects required coverage of exposed vessels
      following tumor resection. All patients in the current study underwent immediate
      reconstruction. RESULTS: The resulting soft tissue defects in this study were due
      to resection of 4 abdominal wall desmoid tumors, a colonic carcinoma infiltrating
      the abdominal wall, 4 primary groin soft tissue sarcomas, a metastatic SCC of the
      leg to groin nodes, and a primary SCC of the groin. The size of the flaps used
      ranged from 20 x 10 cm to 31 x 18 cm. All flaps survived. However, distal flap
      necrosis occurred in 4 cases. Three of those cases developed in flaps
      reconstructing abdominal wall defects, and one case developed in a flap used to
      cover a groin defect. In the former 3 cases, the flap was simply transposed
      without complete islanding of the flap. In the latter case, a very large flap was
      harvested beyond the safe limits with its distal edge just above the knee. In
      addition, wound dehiscence of the flap occurred in 2 other cases from the groin
      132 group. Nevertheless, all the wounds healed spontaneously with repeated
      dressings. Out of the 5 cases that underwent abdominal wall reconstruction, one
      case developed ventral hernia, in which bilateral TFL flaps were used without
      mesh enforcement. There was minimal donor site morbidity in the form of partial
      skin graft loss in 2 cases. The average follow up period in this study ranged
      from 6 months to 2 years. Only one patient died of distant metastasis of a SCC of
      the groin skin, 8 months postoperatively and another 2 patients with abdominal
      desmoid tumors developed local recurrence. CONCLUSION: The tensor fascia lata
      flap is a reliable and a versatile flap, with minimal donor site morbidity.
      Problems with the flap's vascularity of its distal part should not be
      encountered, if the flap is harvested within the safe limits and properly
      designed and the edges comfortably insetted to the defect. A pedicled flap would
      be appropriate for lower abdominal wall defects, and is better islanded to
      achieve extra mobilization and allow a tension free closure, while for groin
      defects, simple flap transposition should be enough. Nevertheless, reconstruction
      for full thickness abdominal wall defects by this flap is a static
      reconstruction. We therefore strongly recommend enforcing the repair with a
      synthetic mesh primarily to minimize the incidence of ventral hernia. However,
      further studies with larger number of cases are needed to confirm this
      observation.

PMID- 16799652
TI  - Quadrantectomy and nipple saving mastectomy in treatment of early breast cancer:
      feasibility and aesthetic results of adjunctive latissmus dorsi breast
      reconstruction.
AB  - BACKGROUND AND PURPOSE: Breast conserving surgery has been a recognised method of
      treatment of early breast cancer. The treatment methods include quadrantectomy or
      skin sparing mastectomy combined with ipsilateral axillary nodal dissection
      followed by radiotherapy. In the current study we evaluate the feasibility and
      oncologic safety of the quadrantectomy and SSM operations with preservation of
      the nipple and areola, and the cosmetic results of immediate reconstruction by
      using the latissmus dorsi flap. MATERIALS AND METHODS: A breast conservative
      surgery (quadrantectomy or nipple sparing mastectomy) was carried out in a group
      of 55 patients with invasive breast cancer treated at the Department of Surgical
      Oncology, NCI, between January 2001 and April 2004. The selection criteria
      included those patients who presented with T1 or T2 breast cancer and were
      located at least 2 cm from the nipple as the centre for the nipple areola
      complex. RESULTS: The age of the patients ranged from 32 years to 65 years. The
      follow up period ranged from 2 to 33 months with an average of 21 months.
      Pathological assessment of the specimens showed a negative safety margin in all
      cases. Most of our cases were invasive duct carcinoma grade 1-2 (42) (75%). The
      complications of the flap reconstruction included one major sloughing of the
      latissmus dorsi flap, 4 partial flap sloughing, 4 sloughing of the nipple and fat
      necrosis in 6 patients. The donor site healed normally in all of our cases except
      for one patient who suffered from a hypertrophic scar which settled down during
      the follow up period. The aesthetic assessment of the patients, showed an
      excellent to good results in the majority of cases (42) (75%) while in 6 (12%)
      results were fair and in 7 (13%) results were poor. CONCLUSION: Breast
      conservative surgery with quadrantectomy or skin sparing technique with
      preservation of the nipple and areola combined with immediate LD flap
      reconstruction is a valid procedure for treatment of early breast cancer.
      Immediate reconstruction by using the extended latissmus dorsi is as safe,
      relatively easy procedure which can provide an adequate volume replacement for
      small to moderate sized breasts.

PMID- 16799653
TI  - Cytoreductive surgery for advanced epithelial tumors of the ovary: technical
      considerations and outcome.
AB  - PURPOSE: To study the role of cytoreductive surgery in the management of advanced
      epithelial tumors of the ovary and its effect on survival. PATIENTS AND METHODS:
      A prospective study of fifty eight female patients presenting with stage III and
      VI epithelial ovarian tumors attending the National Cancer Institute, Cairo
      University during the period from January 2003 to of December 2004. All patients
      were evaluated clinically, radiologically (including plain chest-X-ray and
      abdomino-pelvic ultrasound and/or CT), laboratory work up and CA-125. Abdominal
      exploration under general anesthesia with intent of maximum surgical
      cytoreduction was performed for all patients. Patients were followed up during
      the period of the study by history and physical examination, CA-125 measurement
      and abdomino-pelvic ultrasound or CT. RESULTS: Our study included 58 female
      patients with advanced epithelial tumors of the ovary. Their age ranged from 18
      to 73 years with a mean age of 49 years. Pathological distribution of the lesions
      were borderline malignancy in 5 patients (8.6%) and malignant in 53 patients
      (91.4%). According to FIGO classification there were 46 patients stage III (79%)
      and 12 patients stage VI disease (21%). Eighteen patients (31%) had surgery prior
      to admission to NCI. Cytoreductive surgery was done for 51 patients (88%), while
      7 patients (12%) had exploration and biopsy only, one of whom had palliative
      colostomy for large bowel obstruction. Intraoperative surgical complications were
      encountered in 5 patients (8.6%), all were managed intraoperatively. We had no
      early postoperative mortalities and 8 postoperative morbidities (13.7%). All
      patients were referred for chemotherapy. Thirteen patients (22.4%) had local
      recurrence within the follow up period of the study which was between 8-24
      months. One patient died from locally advanced disease and the rest of the
      patients were explored and lesions were surgically resected. CONCLUSION: Surgery
      remains a major line of therapy in ovarian cancer including advanced lesions.
      Extensive procedures to maintain a R0 result are crucial to reach a satisfactory
      local disease control. The NCI, as well as all tertiary cancer centers, has an
      important role in providing this quality of surgery especially in advanced cases.
      Chemotherapy remains the hope to ameliorate the survival especially in advanced
      cases. The close coordination between surgery and chemotherapy in the form of
      Intra- Peritoneal Hyperthermic Chemotherapy (IPHC) represents a hope for patients
      with advanced disease and should be introduced and established in all major
      cancer centers.

PMID- 16799654
TI  - P-gp expression and Rh 123 efflux assay have no impact on survival in Egyptian
      pediatric acute lymphoblastic leukemia patients.
AB  - PURPOSE: In a previous work we have studied MDR status in terms of P-glycoprotein
      (P-gp) expression and Rhodamine 123 efflux assay in Egyptian acute leukemia
      patients. We have reported results comparable to the literature as regards ANLL
      both in pediatric and adult cases. However, higher figures were encountered for
      the functional assay in ALL. As our ALL cases especially in pediatric age group
      show worse prognosis compared to literature, we hypothesized that the higher
      percentage of cases with positive Rh123 efflux assay might be a contributing
      factor. MATERIAL AND METHODS: A total of 108 cases were studied including 80 ALL
      and 28 ANLL. ALL cases included 48 male and 32 female with an age range of 6m to
      18 yrs and a median of 7 yrs. ANLL cases included 18 male and 10 female with an
      age range of 6m to 18 yrs and a median of 8 yrs. P-gp expression was evaluated
      using 4E3 and UIC2 mAb, analyzed by Coulter XL flow cytometer and expressed as a
      ratio at a cut off of >or= 1.1 and/or >or= 5% positive cells. For the evaluation
      of MDR function Rh123 efflux assay using cyclosporine as a blocker and expressed
      as a ratio at a cutoff of >or= 1.1 and/or >or= 10% positive cells was performed.
      MDR expression and function were correlated to age, Hb, TLC, CD34 expression,
      immunophenotype and DNA index in ALL, FAB subtypes in ANLL as well as to CR, DFS
      and EFS in ALL. RESULTS: In ALL, P-gp expression was encountered in 26.4% of
      cases. Positive Rh efflux was reported in 61.5%. No correlation was encountered
      between neither expression nor functional assay with age, Hb, TLC, CD34
      expression or immunophenotype. CR was achieved in 89.8%; neither P-gp expression
      nor Rh123 efflux had an impact on CR except for Rh123 efflux in T-ALL where a
      cutoff of 1.25 could predict CR at a total accuracy of 70.6%. DFS was 92.3% while
      EFS was 72.2% for the whole group. No significant difference was encountered
      neither between cases expressing or lacking P-gp nor between cases with negative
      or positive Rh123 efflux assay. In ANLL P-gp expression was encountered in 47.6%
      of cases, while positive Rh123 efflux assay was encountered in 75% of cases. No
      correlation as encountered between neither expression nor Rh123 efflux assay and
      neither age, Hb, TLC, CD34 expression nor FAB subtypes. CONCLUSION: Neither P-gp
      expression nor Rh123 efflux assay has any impact on survival in pediatric ALL.
      Rh123 ratio of 1.25 is predictive of CR in TALL.

PMID- 16799655
TI  - Expression and subcellular localization of maspin in human ovarian epithelial
      neoplasms: correlation with clinicopathologic features.
AB  - BACKGROUND AND PURPOSE: Maspin is an inhibitor of serine proteinases with tumor
      suppressor activity that is down-regulated in breast and prostate cancer, but
      overexpressed in pancreatic carcinoma. However, there were very few published
      data regarding the role of maspin in ovarian carcinoma. The aim of the present
      study was to evaluate maspin expression in ovarian epithelial neoplasms and
      correlate its expression with some clinicopathologic parameters. MATERIAL AND
      METHODS: Seventy eight paraffin embedded ovarian specimens from patients with
      ovarian epithelial neoplasms comprised the material of this study. They included
      18 benign, 14 low malignant potential (LMP) and 46 malignant epithelial ovarian
      neoplasms, in addition to seven specimens from normal ovarian tissues as a
      control. RESULTS: Immunohistochemical study of maspin expression using
      streptavidin biotin immunoperoxidase method revealed that, normal ovarian surface
      epithelium did not express maspin as well as benign serous and mucinous ovarian
      epithelial neoplasm. However, all benign Brenner ovarian tumors were maspin
      positive. On the other hand, 57.14% of LMP tumors showed weak maspin expression
      and 63% of malignant ovarian epithelial tumors showed maspin expression with
      39.1% over expression. The two malignant Brenner tumors studied were maspin
      negative. There was a trend for maspin expression with high grade, high stage,
      bilateral tumors and tumors with metastasis. Tumors that showed maspin over
      expression showed higher mitotic index (MI) (p=0.02). Invasive cancers were more
      likely to have predominantly cytoplasmic staining compared to LMP tumors.
      CONCLUSION: Maspin was expressed in a substantial proportion of ovarian tumors
      with poor prognostic parameters. These results may offer new insights regarding
      the role of maspin in ovarian cancer that may also impact diagnosis and treatment
      strategies. Moreover, variation in maspin expression between Brenner tumor and
      other epithelial surface ovarian tumors may indicate that the different
      histological types probably represent distinct disease entities and involve
      different molecular pathways.

PMID- 16799656
TI  - Genetic polymorphism of folate and methionine metabolizing enzymes and their
      susceptibility to malignant lymphoma.
AB  - BACKGROUND: Folate and methionine metabolism is involved in DNA synthesis and
      methylation. Polymorphisms in the genes of folate metabolism enzymes have been
      associated with some forms of cancer. In the present study, 2 polymorphisms were
      evaluated for a folate metabolic enzyme, methylene-tetrahydrofolate reductase
      (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms
      MTHFR 677 C-->T and MTHFR 1298 A-->C, are reported to reduce the enzyme activity,
      which causes intracellular accumulation of 5, 10- methylene-tetrahydrofolate and
      results in a reduced incidence of DNA double strand breakage. The MS 2756 A-->G
      polymorphism also reduces the enzyme activity and results in the hypomethylation
      of DNA. PATIENTS AND METHODS: To test this hypothesis, genetic polymorphisms in
      the folate metabolic pathway were investigated using the DNA from a case-control
      study on 31 patients having malignant lymphoma from the Oncology Outpatient
      Clinic of the New Children's Hospital, Cairo University and 30 controls who were
      actually normal children attending for vaccination to the same hospital. RESULTS:
      We found that there is a higher susceptibility with the MTHFR 677CC and MTHFR
      1298 AA genotypes (OR=4.3, 95% CI 1.12-16). When those harbor at least one
      variant allele in either polymorphism of MTHFR they were defined as reference.
      For the MS 2756 AG genotype polymorphism there was also a higher susceptibility
      to developing malignant lymphoma (OR=2.6; 95% CI 1.1- 6.4). CONCLUSION: Results
      suggest that folate and methionine metabolism may play an important role in the
      pathogenesis of malignant lymphoma. Further studies to confirm this association
      and detailed biologic mechanisms are now required.

PMID- 16799657
TI  - Comparative study of NMP-22, telomerase, and BTA in the detection of bladder
      cancer.
AB  - PURPOSE: The diagnostic efficacy of Nuclear Matrix Protein-22 (NMP-22), bladder
      tumor antigen (BTA TRAK), and telomerase activity was evaluated in urine in a
      trial to assess their value in the detection of bladder cancer and to compare it
      to that of routine urine cytology. SUBJECTS AND METHODS: The study included 46
      newly diagnosed bladder cancer patients, diagnosed by cystoscopy and
      histopathological typing, in addition to 20 patients with benign bladder lesions
      and 20 healthy age and sex matched volunteers as a control group. Fifty percent
      of the cancer patients (23/46) had proven bilharzial history. Most patients
      (27/46) had transitional cell carcinoma (TCC), 17/46 had squamous cell carcinoma
      (SCC), while only 2 patients had adenocarcinoma. A single freshly voided urine
      sample (approximately 100ml) was collected from each patient and control subject
      and aliquoted for each test. All assays were conducted according to the
      manufacturer's guidelines and the results were compared to those of urine
      cytology. RESULTS: The optimal cutoffs for NMP-22, BTA and telomerase activity as
      calculated by ROC curves were 12.1 U/ml, 78 U/ml, 0.48 (Ratio) respectively. The
      levels of the three parameters were significantly higher in the malignant group
      compared to either the benign group or normal controls, (p<0.001) and the
      positive rates were also higher in the malignant group for all 3 parameters. The
      overall sensitivity of urine cytology, NMP-22, BTA and telomerase was 54.3%,
      91.3%, 100% and 80.4% respectively. For bilharzial cancer bladder respective
      sensitivities were 69.6%, 95.6%, 100% and 73.9%, while for nonbilharzial cancer
      bladder the respective sensitivities were 39.1%, 87%, 100% and 87%. The overall
      specificities with urine cytology, NMP-22, BTA and telomerase was 100%, 87.5%,
      92.5% and 95.0%, respectively. Combined sensitivity of voided urine cytology with
      one or more of the 3 biomarkers, or the use of these biomarkers in double or
      triple combinations gave higher positivity than each biomarker alone. CONCLUSION:
      BTA showed the highest sensitivity in all the studied parameters in the bladder
      cancer group, bilharzial bladder cancer subgroup, and non bilharzial bladder
      subgroup, (100%), while the highest specificity was recorded with urine cytology
      (100%), followed by telomerase (95%), then BTA (92.5%), and lastly NMP- 22
      (87.5%). Use of markers in combination with cytology, or in a panel, improved the
      sensitivity, and specificity.

PMID- 16799659
TI  - Ru106 brachytherapy for management of choroidal melanoma: do we need to adjust
      total dose according to the new NIST calibration measurement?
AB  - PURPOSE: To detect the need of adjusting the apical total dose according to the
      new NIST calibration measurement introduced by BEBIG Isotopen und Medizintechnik
      GmbH for the treatment of choroidal melanoma. As the total radiation dose should
      not be individualized depending on errors pf previous calibration but can be
      applicable if based on a radiosensitivity test that was able to predict the final
      response of tumor to radiation for each particular patient. PATIENTS AND METHODS:
      Twenty patients with choroidal melanomas were treated between November 2002 and
      July 2004 at "Suzanne Mubarak Eye Tumor Centre", National Eye centre Rod-EL
      Farag, Cairo, Egypt. The prescribed dose was calculated according to the new
      NISTcalibrated dosimetry introduced by BEBIG, but without dose modification by
      using a conversion factor F(type,z) from the ASMW calibrated measurement to the
      NIST calibrated measurement that have been calculated depending on the plaque
      type and the distance z from the inner concave plaque surface along the central
      axis. For the treatment of choroidal melanoma in this study the apical dose
      ranged from 9000-10400cGy with a mean of 9855 +/- 385. RESULTS: After a follow up
      period from 12-28 months (median of 19 months) there was a local control rate of
      100 % and the three years actuarial disease specific survival was 95% as only one
      patient died of liver metastases. Fourteen patients had a best corrected pre
      treatment visual acuity of better than 6/60 in the affected eye. At the last
      follow up available, useful visual acuity of>0.5 was preserved in 7 of the
      patients. CONCLUSION: Recalculation of the apical total dose (mostly increasing
      of the total dose) according to the conversion factor F(type,z), suggested by
      BEBIG after the new NIST calibration measurement, does not seem to have an effect
      on both local control and survival, in this study.

PMID- 16799658
TI  - Planning of the internal mammary field based on lymphoscintigraphy localization
      before postoperative radiotherapy of breast cancer.
AB  - BACKGROUND: Internal mammary irradiation is still an issue of great debate.
      Although treatment of internal mammary lymph nodes was routinely given in the
      majority of randomized trials, data in its value are still limited. The aim of
      this study is to determine the variability of position of the internal mammary
      lymph nodes using lymphoscintigraphy and to compare the dose of radiation that
      reaches these lymph nodes, the heart and lungs if only tangential fields are
      used. MATERIAL AND METHODS: This is a prospective study that included 30 breast
      cancer patients treated in the department of radiation oncology of the Egyptian
      National Cancer Institute, Cairo University, planned for postoperative
      radiotherapy. Lymphoscintigraphy was done for all patients for detection of the
      exact site of the internal mammary lymph nodes. Dose volume histogram (DVH) was
      done to measure the dose to the heart using CT planning. Two plans were done for
      each patient, the first with internal mammary field (plan I), and the second
      without but with contralateral crossing of the midline by 1cm (plan II). RESULTS:
      The mean percentage of the internal mammary lymph nodes included in the internal
      mammary field (plan I) was 70.03% while in plan II it was 3.05%. The mean dose
      percentage reaching the heart in plan I was 54.5% of total dose, while in plan II
      it was 9.16% of total dose with significant p value<0.001. The mean dose to the
      heart decreased as the heart volume increased, this significant difference
      between the 2 plans was maintained for the different heart volumes. Also, the
      radiation dose to the heart in plan I varied significantly (p: 0.001) between the
      right side vs the left side with a mean dose of 48.02% and 63.5%, respectively.
      The mean dose percentage reaching the lungs in plan I and plan II was 46.53% and
      24.5% respectively, with significant p value<0.001. CONCLUSION: If irradiation of
      internal mammary chain is intended, then a direct internal mammary field should
      be used. The planning of internal mammary field should be adjusted according to
      lymphoscintigraphy so as to include most of the draining internal mammary lymph
      nodes. The risk of late cardiac and pulmonary complications will increase when
      using direct internal mammary field, but the risk of cardiac complications will
      be less in irradiation of right side internal mammary lymph nodes compared to
      that of irradiation of the left side.

PMID- 16799660
TI  - Numerical simulation of speckle noise in laser vibrometry.
AB  - The fundamental mechanism by which speckle noise is generated in laser vibrometry
      before describing a new numerical simulation for prediction of speckle noise
      level in a real measurement is considered. Factors within the simulation include
      rate of change of phase within individual speckle transitions, low-pass filtering
      to match the frequency range of experimental data with which comparison is to be
      made, a track-and-hold facility for periods of low signal amplitude, and
      wavefront curvature effects. The simulation data provide real insight into the
      phase and amplitude modulation of the Doppler signal, and good agreement is found
      in the final comparison with experimental data from a measurement on a rotating
      target.

PMID- 16799662
TI  - Design of high-performance supersphere solid immersion lenses.
AB  - Two types of novel solid immersion lens are designed and investigated
      theoretically using the vector diffraction theory. The advantages of these so
      called high-performance supersphere solid immersion lenses (HPSILs) are that they
      can improve the Strehl ratio of the focused spot and increase the focal depth of
      near-field optical systems. Both the spot size and the sidelobe intensity are not
      increased, however, compared with those of the standard Weierstrass solid
      immersion lens. These HPSILs will be useful for near-field optical data storage
      and photolithography.

PMID- 16799661
TI  - Simultaneous two-dimensional endoscopic pulsed digital holography for evaluation
      of dynamic displacements.
AB  - An endoscope is used in pulsed digital holography to simultaneously evaluate in
      plane and out- of-plane transient and harmonic displacements on a flat metallic
      plate. The plate is illuminated from two different directions. The optical path
      for each illumination direction is matched to its corresponding reference beam,
      but also in such a way that each object-reference beam pair optical path is
      mismatched such that they are incoherent and can be stored in a single CCD frame.
      As is typical in these types of interferometric arrangement, two digital
      holograms are needed to compare two different states of the plate. Each hologram
      is Fourier transformed and due to the incoherence introduced, two separate
      spectra are readily identified, each belonging to an object-reference beam pair.
      On comparing by subtraction the phase obtained from the two pulsed digital
      holograms, it is possible to gather quantitative in-plane and out-of- plane
      results from transient and harmonic displacements.

PMID- 16799663
TI  - Determination of optical parameters and thickness of weakly absorbing thin films
      from reflectance and transmittance spectra.
AB  - A method for determining the optical constants and the thickness of weakly
      absorbing thin films on substrates is proposed. In this method only the
      reflectance and transmittance spectra obtained at a single arbitrary angle of
      incidence are used, provided that the former reveals several interference
      extrema. The calculation procedure is based on relatively simple relations
      suitable for the programmed realization and does not call for the prescription of
      the initial values of the parameters to be determined. The method proposed is
      fairly accurate and allows one to uniquely solve the inverse problem of
      spectrophotometry. The optical constants and the thickness of an As(x)Se(y) film
      formed on a glass substrate have been determined by the proposed method in the
      visible region of the spectrum.

PMID- 16799664
TI  - Pixelated mask spatial carrier phase shifting interferometry algorithms and
      associated errors.
AB  - In both temporal and spatial carrier phase shifting interferometry, the primary
      source of phase calculation error results from an error in the relative phase
      shift between sample points. In spatial carrier phase shifting interferometry,
      this phase shifting error is caused directly by the wavefront under test and is
      unavoidable. In order to minimize the phase shifting error, a pixelated spatial
      carrier phase shifting technique has been developed by 4D technologies. This new
      technique allows for the grouping of phase shifted pixels together around a
      single point in two dimensions, minimizing the phase shift change due to the
      spatial variation in the test wavefront. A formula for the phase calculation
      error in spatial carrier phase shifting interferometry is derived. The error
      associated with the use of linear N-point averaging algorithms is presented and
      compared with those of the pixelated spatial carrier technique.

PMID- 16799665
TI  - Simple interferometric fringe stabilization by charge-coupled-device-based
      feedback control.
AB  - A method for producing stabilized interference patterns for ultraviolet
      interference lithography using a CCD camera as the detector element is described.
      Intensity data obtained from the CCD element are filtered in software to minimize
      speckle and detector noise effects as well as to determine the relative phase of
      the interfering beams. A control signal is then issued to correct the fringe
      drift. The system allows rapid reconfiguration of the lithography setup with
      minimum realignment of optical components.

PMID- 16799666
TI  - Optical fiber long-period grating humidity sensor with poly(ethylene
      oxide)/cobalt chloride coating.
AB  - A long-period fiber grating (LPFG) humidity sensor is reported utilizing
      poly(ethylene oxide)/cobalt chloride (PEO/CoCl2) as a hybrid hygrosensitive
      cladding coating. A thin overlay of the material is deposited on the LPFG and
      with exposure to different ambient humidity levels, its spectral properties are
      modified. The material parameters associated with the sensing mechanism may
      include those of refractive index, absorption, and morphological alterations of
      the overlaid material. Relative humidity variations in the range from 50% to 95%
      have been detected with a resolution better than 0.2%. The response time constant
      of the fiber sensor is of the order of a few hundred milliseconds.

PMID- 16799667
TI  - Infrared broadband 50%-50% beam splitters for s-polarized light.
AB  - Prisms and slabs made of high-refractive-index materials such as ZnSe, Ge, and Si
      can be designed as broadband, 50%-50%, beam splitters (BSs) for obliquely
      incident s- polarized light in the near- and mid-IR. The beam-splitting face of
      the prism or slab is uncoated, while the exit face is antireflection coated. The
      split beams travel in orthogonal directions when light is incident at the
      Brewster angle. A novel design is also described that uses Brewster-angle
      reflection at the SiO2-Si interface to achieve a 50%-50%s-polarization BS over
      the 1.2-3.5 microm spectral range. Such s-polarization BSs are particularly
      suited for interferometry and holography.

PMID- 16799668
TI  - Electrically tunable lens based on a dual-frequency nematic liquid crystal.
AB  - We report on an electrically controlled liquid-crystal-based variable optical
      lens filled with a dual-frequency nematic material. The lens design employs a
      hole-patterned electrode structure in a flat nematic cell. In order to decrease
      the lens switching time we maximize the dielectric torque by using a dual
      frequency nematic material that is aligned at an angle approximately 45 degrees
      with respect to the bounding plates by obliquely deposited SiO(x), and by using
      an overdrive scheme of electrical switching. Depending on the frequency of the
      applied field, the director realigns either toward the homeotropic state
      (perpendicular to the substrates) or toward the planar state (parallel to the
      substrates), which allows one to control not only the absolute value of the focal
      length but also its sign. Optical performance of the liquid-crystal lens is close
      to that of an ideal thin lens.

PMID- 16799669
TI  - Flatfielding in spatial heterodyne spectroscopy.
AB  - Spatial heterodyne spectroscopy (SHS) is a Fourier-transform spectroscopic
      technique that simultaneously records all path differences using a detector
      array. Compared to conventional Fourier-transform spectroscopy that measures
      interferogram samples sequentially in the time domain, SHS is insensitive to a
      changing scene; however, the effects caused by differences in the detector
      elements and/or the optics for each sample must be addressed with a flatfield
      correction. The flatfield correction is typically a characteristic of the
      instrument and does not change with the observed scene. We present three
      different flatfielding approaches. Each is based on different assumptions and is
      applicable depending on the instrumental effects dominating the flatfield.

PMID- 16799670
TI  - Determination of the optical constants (n and k) of inhomogeneous thin films with
      linear index profiles.
AB  - A new method for the determination of optical constants of absorbing
      inhomogeneous thin films is proposed. It requires measurements at normal
      incidence of the reflectance and transmittance of the film. In an inhomogeneous
      thin film, the optical constants vary along the thickness of the film. It has
      been reported in the literature that only the spatial integral value of the
      absorption index needs to be considered if its value is small. Therefore, in the
      proposed method, the mean value of the absorption index was used. The validity of
      this assumption was tested. On the other hand, the variation in the refractive
      index along the thickness of the film was taken into account. The method is
      discussed along with the nature of the solutions obtained and the effects of
      various parameters and assumptions. The method is applied successfully to
      inhomogeneous thin films of zirconium oxide.

PMID- 16799671
TI  - Optical properties of fluoride thin films deposited by RF magnetron sputtering.
AB  - Fluoride thin films for 193-nm lithography were deposited by three different
      types of RF magnetron sputtering. Systematic analysis of the relation between
      optical properties and deposition conditions of these thin films is discussed.

PMID- 16799672
TI  - Finite-difference field calculations for two-dimensionally confined x-ray
      waveguides.
AB  - A numerical method for calculation of the electromagnetic field in two
      dimensionally confined x-ray waveguides is presented. It is based on the
      parabolic wave equation, which is solved by means of a finite-difference scheme.
      The results are verified by a comparison to analytical theory, namely, Fresnel
      reflectivity and the weakly guiding optical fiber.

PMID- 16799673
TI  - Wolter type I x-ray focusing mirror using multilayer coatings.
AB  - A multilayer coating is a useful addition to a mirror in the x-ray region and has
      been applied to normal incidence mirrors used with soft x rays. When a multilayer
      coating is used on grazing incidence optics, higher performance can be achieved
      than without it. Cr/Sc multilayers coated on a Wolter type I mirror substrate for
      a soft x-ray microscope are considered. The reflectivity and effective solid
      angle are calculated for Wolter type I mirrors with uniform and laterally graded
      multilayer coatings. The laterally graded multilayer mirror showed superior x-ray
      performance, and the multilayer tolerances were relaxed. This multilayer mirror
      could be especially useful in the soft x-ray microscope intended for biological
      applications.

PMID- 16799674
TI  - Performance comparison of iterative algorithms for generating digital correlation
      holograms used in optical security systems.
AB  - An optical security system based on a correlation between two separate binary
      computer-generated holograms has been developed and experimentally tested. The
      two holograms are designed using two different iterative algorithms: the
      projection- onto constrained sets algorithm and the direct binary search (DBS)
      algorithm. By placing the ready-to-use holograms on a modified joint transform
      correlator input plane, an output image is constructed as a result of a spatial
      correlation between the two functions coded by the holograms. Both simulation and
      experimental results are presented to demonstrate the system's performance. While
      we concentrate mainly on the DBS algorithm, we also compare the performance of
      both algorithms.

PMID- 16799675
TI  - Single beam one-way imaging through a thick dynamic turbulent medium.
AB  - A new method to record an image through a thick dynamic phase distorting medium
      by using a photorefractive LiNbO3 crystal is demonstrated. The method uses only
      one beam of light, the object light. By making use of the photorefractive fanning
      effect, gratings are formed in the LiNbO3 crystal through the interference
      between the object light and its own fanning light. Because the time scale of the
      distorting fluctuation is much shorter than the writing time of the LiNbO3
      crystal, the fluctuated light does not induce any fanning. Therefore only the
      static portion of the image is recorded in the crystal, and the intensity
      distribution of the image can then be reconstructed at any later time.

PMID- 16799677
TI  - Deconvolution of axisymmetric flame properties using Tikhonov regularization.
AB  - We present a method based on Tikhonov regularization for solving one-dimensional
      inverse tomography problems that arise in combustion applications. In this
      technique, Tikhonov regularization transforms the ill-conditioned set of
      equations generated by onion-peeling deconvolution into a well-conditioned set
      that is less susceptible to measurement errors that arise in experimental
      settings. The performance of this method is compared to that of onion-peeling and
      Abel three-point deconvolution by solving for a known field variable distribution
      from projected data contaminated with an artificially generated error. The
      results show that Tikhonov deconvolution provides a more accurate field
      distribution than onion-peeling and Abel three-point deconvolution and is more
      stable than the other two methods as the distance between projected data points
      decreases.

PMID- 16799676
TI  - Magnification of 3D reconstructed images in integral imaging using an
      intermediate-view reconstruction technique.
AB  - A new integral imaging (II) system that can magnify 3D reconstructed images by
      employing an intermediate-view reconstruction technique (IVRT) is proposed in
      which the number of the elemental images obtained from a one-step pickup process
      can be computationally increased by use of an IVRT without mechanical movement
      and a long multistep pickup process. To show the feasibility of the proposed II
      system, some optical experiments on the magnification of 3D reconstructed images
      with a real 3D object have been carried out and results are presented.

PMID- 16799678
TI  - Fuzzy-logic optical optimization of mainframe CPU and memory.
AB  - The allocation of CPU time and memory resources is a familiar problem in
      organizations with a large number of users and a single mainframe. Usually the
      amount of resources allocated to a single user is based on the user's own
      statistics not on the statistics of the entire organization, therefore patterns
      are not well identified and the allocation system is prodigal. A fuzzy-logic
      based algorithm to optimize the CPU and memory distribution among users based on
      their history is suggested. The algorithm works on heavy and light users
      separately since they present different patterns to be observed. The result is a
      set of rules generated by the fuzzy-logic inference engine that will allow the
      system to use its computing ability in an optimized manner. Test results on data
      taken from the Faculty of Engineering of Tel Aviv University demonstrate the
      capabilities of the new algorithm.

PMID- 16799679
TI  - Threshold algorithm to recover the deformation of optical surfaces.
AB  - The global optimization threshold algorithm is reported to obtain the
      deformations of an optical surface. The advantage of these types of algorithm is
      that they can be solved for the correlation problem presented in Seidel
      polynomials. We obtain the 2D deformations of a surface test with the transversal
      aberration along one direction only. In order to apply this algorithm we used
      exact ray tracing to simulate the transversal aberration adapting the same
      mathematical theory for the Ronchi test. The error obtained in sagitta recovering
      deformation was 1 microm.

PMID- 16799680
TI  - Optical cross-connect system based on the White cell and three-state
      microelectromechanical system: experimental demonstration of the quartic cell.
AB  - We present a proof of concept (design, simulations, and experimental results) for
      an optical cross-connection device based on the optical White cell and a three
      state microelectromechanical system tilting mirror array. We describe in detail
      the implementation of an underpopulated quartic White cell configuration. We
      discuss the aberrations associated with the output of the system.

PMID- 16799681
TI  - Size determination by use of two-dimensional Mueller matrices backscattered by
      optically thick random media.
AB  - Here we are concerned with the systematic study of polarized light transport in
      thick, isotropic, homogeneous random media and of the associated inverse problem.
      An original spatial and intensity rescaling of the polarization transport allows
      one to account implicitly for the volume fraction. This parameter elimination
      permits a complete exploration, by means of Monte Carlo simulations of the
      dependence of polarized light transport on microscopic parameters. Analysis of
      the Mueller matrices obtained from the simulations show that additional
      correlations (with respect to scalar transport) are obtained between the
      microscopic parameters and the spatial distribution of specific elements of the
      Mueller matrix. As a consequence, using carefully chosen polarization states, one
      can determine an average particle size independently of the volume fraction of
      particles, with only the knowledge of the refractive-index ratio being required.
      This analysis is validated with experimental Mueller matrices obtained for
      emulsions of various size, concentration, and polydispersity.

PMID- 16799682
TI  - Photothermal effects in fiber Bragg gratings.
AB  - Writing a fiber Bragg grating in optical fiber generates an intrinsic broadband
      absorption term that can result in photothermal heating during subsequent use
      with fiber core guided light. This, in turn, can cause a significant shift of a
      grating resonance via the thermo-optic coefficient, even at low in-fiber light
      powers. The magnitude of the absorption term and its dependence on the grating
      strength are detailed. We further show how the degree of heating can be
      influenced by the particular environment in which the grating is placed and that,
      while the shift can be quite deleterious for some applications, its effect can be
      mitigated. A simple conductive model is developed.

PMID- 16799683
TI  - Impact of interferometer optical path difference speed profile on the Fourier
      transform-spectrometry-derived spectrum of a telecommunications signal.
AB  - The impact of the interferometer optical path difference (OPD) speed profile on
      the spectrum, derived through the use of Fourier-transform spectrometry (FTS), of
      a synchronous optical network (SONET) signal is found. The SONET signal carries
      high-speed data traffic. It also may be modulated by low-frequency intensity or
      frequency modulation. It is found that the SONET header, high-speed data traffic
      and low-frequency modulation all manifest themselves as artifacts in the FTS
      derived spectrum of the SONET signal. It is shown that a nonconstant OPD speed
      profile can smooth out these artifacts, making it unlikely that they will be
      mistaken for carrier signal peaks. However, it is found that smoothing out these
      artifacts lessens the achievable dynamic range of the FTS instrument in the
      frequency range of interest, the International Telecommunications Union common
      (C) and long (L) bands.

PMID- 16799684
TI  - Numerical simulation of the amplification of a short laser pulse by a ytterbium
      doped amplifier longitudinally pumped by short pump pulses.
AB  - A simple and original derivation making it possible to analytically compute the
      performances achievable with an end pumped ytterbium (Yb) amplifier pumped by a
      pump pulse and seeded by a laser pulse both shorter than the upper-level lifetime
      is presented. This may be useful when amplifiers or lasers are pumped by a
      Ti:sapphire laser. The case of a Yb:YAG amplifier is numerically investigated and
      it is shown that, in these conditions, the resulting efficiency can reach quantum
      efficiency.

PMID- 16799685
TI  - Numerical model of wavelength conversion through cross-gain modulation in
      semiconductor optical amplifiers.
AB  - A steady-state numerical model of wavelength conversion through cross-gain
      modulation in semiconductor optical amplifiers is described, which includes the
      spatial variations of the carrier density, gain coefficient, differential gain,
      and internal loss. Of particular interest is the analytic gain coefficient model,
      which is applied to the semiconductor optical amplifier converter problem for the
      first time to our knowledge. The model is used to compare performances of
      upconverters and downconverters for cases of long and short device lengths, and
      in large and small signal regimes. Comparisons with results of other studies are
      presented.

PMID- 16799686
TI  - Development of line-shaped optical system for green laser annealing used in the
      manufacture of low-temperature poly-Si thin-film transistors.
AB  - We have developed a new optical system that transforms the circle profile beam
      generated with near-Gaussian intensity distribution by a pulse green laser
      (YAG2omega laser; second harmonics of a Q-switched Nd:YAG laser) into a line
      profile beam. For homogenization in the longitudinal direction, we employed a
      waveguide plate-type homogenizer. We successfully reduced interference fringes.
      In the width direction, the laser beam was focused up to the limited M2 value.
      This transformed beam has a uniform distribution to within 5% in the longitudinal
      direction, and it is approximately 100 mm long and 40 microm wide.

PMID- 16799687
TI  - Fluorescence dynamics and rate equation analysis in Er3+ and Yb3+ doped double
      tungstates.
AB  - The fluorescence dynamics in Er3+ and Yb3+ doped KGd(WO4)2 and KY(WO4)2 has been
      investigated. Lifetimes have been measured for the Yb (2F(5/2)), Er (4I(13/2)),
      and Er (4S(3/2)) levels around 1, 1.5, and 0.55 microm, respectively. The Yb
      (2F(5/2)) lifetimes show a decreasing trend toward the limiting Er (4I(11/2))
      lifetime with increasing Er-to-Yb concentration ratio, whereas the Er (4I(13/2))
      lifetimes are mostly unaffected by the doping concentrations. A rate equation
      analysis has been performed to explain the observed behavior and gain is
      calculated for a continuous-wave laser at 1.53 microm to find the optimum doping
      concentrations for high gain.

PMID- 16799688
TI  - Underwater light polarization and radiance fluctuations induced by surface waves.
AB  - The underwater light field is an ever-changing environment. Surface waves induce
      variability in the radiance and the light's polarization. We examined the
      dependence of the polarization fluctuations associated with diffuse light (not
      including contribution from direct skylight) on the viewing zenith angle (30
      degrees, 70 degrees, and 90 degrees), solar zenith angle (23 degrees -72
      degrees), depth of 0.5-3 m, and light wavelength (380-650 nm) while observing
      within the azimuthal plane in the wind-wave direction. Polarization and radiance
      fluctuated with time. Light variability (presented by the coefficient of
      variation calculated over a series of fluctuations in the radiance and percent
      polarization, and by the standard deviation calculated over a series of
      fluctuations in the e-vector orientation) was highest at a viewing zenith angle
      of 70 degrees , depended positively on the solar zenith angle, and decreased with
      depth at viewing zenith angles of 30 degrees and 70 degrees . Additionally, the
      variability of the percent polarization was significantly higher than that of the
      radiance. The temporal light fluctuations offer possibilities, such as enhancing
      the detection of transparent and reflecting objects; however, they set
      constraints on the optimal underwater polarization vision by both animals and by
      the use of instruments.

PMID- 16799689
TI  - Group velocity dispersion using commercial optical design programs.
AB  - Three commercial optical design programs are used to model familiar geometries in
      ultrafast optics. A set of macros has been created to calculate the pulse delay,
      group velocity dispersion, and third-order dispersion caused by the components in
      an ultrafast optical system. The results correspond to published values. This
      opens the possibility of using the well-developed optimization routines to
      improve the performance of ultrafast systems.

PMID- 16799690
TI  - Effective scattering coefficient of the cerebral spinal fluid in adult head
      models for diffuse optical imaging.
AB  - An efficient computation of the time-dependent forward solution for photon
      transport in a head model is a key capability for performing accurate inversion
      for functional diffuse optical imaging of the brain. The diffusion approximation
      to photon transport is much faster to simulate than the physically correct
      radiative transport equation (RTE); however, it is commonly assumed that
      scattering lengths must be much smaller than all system dimensions and all
      absorption lengths for the approximation to be accurate. Neither of these
      conditions is satisfied in the cerebrospinal fluid (CSF). Since line-of-sight
      distances in the CSF are small, of the order of a few millimeters, we explore the
      idea that the CSF scattering coefficient may be modeled by any value from zero up
      to the order of the typical inverse line-of-sight distance, or approximately 0.3
      mm(-1), without significantly altering the calculated detector signals or the
      partial path lengths relevant for functional measurements. We demonstrate this in
      detail by using a Monte Carlo simulation of the RTE in a three-dimensional head
      model based on clinical magnetic resonance imaging data, with realistic optode
      geometries. Our findings lead us to expect that the diffusion approximation will
      be valid even in the presence of the CSF, with consequences for faster solution
      of the inverse problem.

PMID- 16799691
TI  - Effects of the surface boundary on the determination of the optical properties of
      a turbid medium with time-resolved reflectance.
AB  - Solutions of the time-dependent diffusion equation were developed to take into
      account the depth of the source and the detector inside a semi-infinite medium.
      These solutions permitted an evaluation of optical properties at different depths
      below the surface by fitting time-resolved data. Measurements were performed on
      liquid optical phantoms with optical fibers for delivering and collecting light.
      A time-correlated single-photon-counting chain was used for electronic detection.
      The determination of optical properties underlines the continuity between the
      surface model and the infinite model and shows the depth at which the derived
      solutions can be applied.

PMID- 16799692
TI  - Consideration of a spread-out source in problems of near-infrared optical
      tomography.
AB  - When the light propagates in media where absorption is not negligible and/or
      scattering is weak, a contribution to the energy density coming from ballistic
      photons cannot be neglected. A point source effectively spreads out over a
      scattering volume and its spatial distribution is described by the source
      function. We consider a boundary value problem of light propagation in half-space
      for such a source on the basis of the telegraph equation. A solution is found by
      convolution of Green's function with the source function. The final result shows
      a significant difference in the behavior of the radiant energy density between
      the solution obtained for a distributed source and the diffusion approximation.
      Our results agree well with the Monte Carlo simulations over a broad range of
      scattering and/or absorption conditions. The obtained results are of practical
      importance in luminescence optical tomography because an erroneous shape of the
      energy density function may lead to an incorrect estimate of the light source
      depth after image reconstruction. The range of applications of the diffusion
      approximation is also discussed.

PMID- 16799693
TI  - Sequential estimation of optical properties of a two-layered epithelial tissue
      model from depth-resolved ultraviolet-visible diffuse reflectance spectra.
AB  - A method for estimating the optical properties of two-layered media (such as
      squamous epithelial tissue) over a range of wavelengths in the ultraviolet
      visible spectrum is proposed and tested with Monte Carlo modeling. The method
      first used a fiber-optic probe with angled illumination and the collection fibers
      placed at a small separation (<or=300 microm) to restrict the transport of
      detected light to the top layer. A Monte Carlo-based inverse model for a
      homogeneous medium was employed to estimate the top layer optical properties from
      the measured diffuse reflectance spectrum. Then a flat-tip probe with a large
      source-detector separation (>or=1000 microm) was used to detect diffuse
      reflectance preferentially from the bottom layer. A second Monte Carlo-based
      inverse model for a two-layered medium was applied to estimate the bottom layer
      optical properties, as well as the top layer thickness, given that the top layer
      optical properties have been estimated. The results of Monte Carlo validation
      show that this method works well for an epithelial tissue model with a top layer
      thickness ranging from 200 to 500 microm. For most thicknesses within this range,
      the absorption coefficients were estimated to within 15% of the true values, the
      reduced scattering coefficients were estimated to within 20% and the top layer
      thicknesses were estimated to within 20%. The application of a variance reduction
      technique to the Monte Carlo modeling proved to be effective in improving the
      accuracy with which the optical properties are estimated.

PMID- 16799694
TI  - Techniques of EMG signal analysis: detection, processing, classification and
      applications.
AB  - Electromyography (EMG) signals can be used for clinical/biomedical applications,
      Evolvable Hardware Chip (EHW) development, and modern human computer interaction.
      EMG signals acquired from muscles require advanced methods for detection,
      decomposition, processing, and classification. The purpose of this paper is to
      illustrate the various methodologies and algorithms for EMG signal analysis to
      provide efficient and effective ways of understanding the signal and its nature.
      We further point up some of the hardware implementations using EMG focusing on
      applications related to prosthetic hand control, grasp recognition, and human
      computer interaction. A comparison study is also given to show performance of
      various EMG signal analysis methods. This paper provides researchers a good
      understanding of EMG signal and its analysis procedures. This knowledge will help
      them develop more powerful, flexible, and efficient applications.

PMID- 16799695
TI  - Cell-based expression cloning for identification of polypeptides that
      hypersensitize mammalian cells to mitotic arrest.
AB  - Microtubule inhibitors such as Vinblastine and Paclitaxel are chemotherapy agents
      that activate the mitotic spindle checkpoint, arresting cells in mitosis and
      leading to cell death. The pathways that connect mitotic arrest to cell death are
      not well characterized. We developed a mammalian cell-based cDNA cloning method
      to isolate proteins and protein fragments whose expression inhibits colony
      formation in the presence of microtubule inhibitors. Understanding how these
      proteins impact cellular responses to microtubule drugs will lead to better
      understanding of the biochemical pathways connecting mitotic arrest and cell
      death in mammalian cells and may provide novel targets that can enhance
      microtubule inhibitor-mediated chemotherapy.

PMID- 16799696
TI  - Use of chromatin immunoprecipitation (ChIP) to detect transcription factor
      binding to highly homologous promoters in chromatin isolated from unstimulated
      and activated primary human B cells.
AB  - The Chromatin Immunoprecipiation (ChIP) provides a powerful technique for
      identifying the in vivo association of transcription factors with regulatory
      elements. However, obtaining meaningful information for promoter interactions is
      extremely challenging when the promoter is a member of a class of highly
      homologous elements. Use of PCR primers with small numbers of mutations can limit
      cross-hybridization with non-targeted sequences and distinguish a pattern of
      binding for factors with the regulatory element of interest. In this report, we
      demonstrate the selective in vivo association of NF-kappaB, p300 and CREB with
      the human Igamma1 promoter located in the intronic region upstream of the Cgamma1
      exons in the immunoglobulin heavy chain locus. These methods have the ability to
      extend ChIP analysis to promoters with a high degree of homology.

PMID- 16799698
TI  - Permeability of R6G across Cx43 hemichannels through a novel combination of patch
      clamp and surface enhanced Raman spectroscopy.
AB  - We have measured the permeability of rhodamine-6G across Cx43 hemichannels
      reconstituted on a pipette tip. Cx43 hemichannels were overexpressed in Sf9
      cells, and affinity-purified. The hemichannels were reconstituted in a lipid
      bilayer on a pipette tip by the tip-dip method. R6G in the pipette permeated
      across the channels into the bath. The permeability of R6G was quantified by
      measuring R6G concentration in the bath after several hours by surface enhanced
      Raman spectroscopy (SERS) with 100 nm silver colloid particles. The ratio of the
      permeability of dye to salt, as extracted by this combined electrical-SERS
      technique, is compatible with similar ratios for other dyes across whole gap
      junction channels. The results for the permeability ratio were further compared
      to fluorescence measurements. The novel combination of patch and SERS techniques
      can be extended to quantifying the transport of biologically significant non
      fluorescent molecules, such as cAMP and IP3, across 1 nm sized pores, such as the
      gap junction channel.

PMID- 16799697
TI  - Treatment of Social Phobia: Potential Mediators and Moderators.
AB  - Although the efficacy of numerous psychosocial interventions for social phobia
      has been clearly demonstrated, little is known about the mediators and moderators
      of treatment change. Three potential mediators are discussed that are derived
      from prominent psychological theories: negative cognitive appraisal (estimated
      social costs), perceived self-efficacy (perceived social skills), and perceived
      emotional control. Furthermore, the generalized subtype of social phobia and the
      additional diagnosis of avoidant personality disorder are considered as potential
      treatment moderators.

PMID- 16799699
TI  - A PERSON-CENTERED AND ECOLOGICAL INVESTIGATION OF ACCULTURATION STRATEGIES IN
      HISPANIC IMMIGRANT YOUTH.
AB  - Understanding the processes of acculturation in ethnic minority populations is
      one of the central tasks of crosscultural research. Addressing challenges of
      theory, methods, and application in acculturation research requires ongoing
      advancements in methods and theoretical and model development. The current study
      was designed to explain a person-centered approach to investigating acculturation
      and biculturalism and to illustrate this method with a sample of 315 Hispanic
      youth. Pattern analyses of the Hispanicism and Americanism scores from the
      Bicultural Involvement Scale yielded four distinct acculturation types, including
      one characterized by moderate scores on both scales. Relations between
      acculturation types and indicators of individual, family, and peer adaptation
      were tested. Results indicated that bicultural youth tended to show the most
      adaptive pattern of functioning across multiple sociocultural domains.
      Assimilated youth did not show as strongly negative a pattern as has been
      reported elsewhere. Implications and benefits of a person-centered approach are
      discussed.

PMID- 16799700
TI  - NATIVITY AND YEARS IN THE RECEIVING CULTURE AS MARKERS OF ACCULTURATION IN ETHNIC
      ENCLAVES.
AB  - The current study was conducted to ascertain the validity of two commonly used
      markers of acculturation (nativity and years in the receiving culture) in an
      enclave context. Relationships between these markers and a bidimensional measure
      of acculturation were examined in a convenience sample of Hispanic immigrant
      adolescents and their caregivers in Miami. Nativity was examined using adolescent
      reported data; approximately half of the youth were U.S.-born and half foreign
      born, but all of the caregivers were foreign-born. Years in the receiving culture
      was examined using both adolescent and caregiver data. Results indicated that
      nativity was significantly associated with adoption of receiving-culture
      practices, with a small to moderate effect size. Years in the receiving culture
      was significantly associated with adoption of receiving-culture practices only
      for adolescent girls and for female caregivers who immigrated as youth. Neither
      nativity nor years in the receiving culture explained even moderate amounts of
      variance in retention or loss of culture-of-origin practices.

PMID- 16799701
TI  - Differential Predictors of African American and Hispanic Parent Retention in a
      Family-Focused Preventive Intervention.
AB  - Similarities and differences in predictors of retention/attendance patterns
      between African American and Hispanic parent participants (N = 143) from a family
      focused preventive intervention were examined. Three broad retention pattern
      groups, nonattenders, variable attenders, and consistent high attenders, and 2
      subgroups of the variable attendance group, decreasing low attenders and
      decreasing high attenders, were identified. In subgroup analyses, 3 significant
      discriminant functions were evident: 1 function classified Hispanic parents'
      retention patterns using sociodemographic indicators (e.g., educational
      attainment, household income) and 2 functions discriminated Hispanic and African
      American parents' patterns using family-level predictors (e.g., multiple
      caregivers attending the intervention, perceived barriers to participation).
      Implications are discussed in terms of strategies for improving methods of
      retaining participants in family-centered interventions conducted with ethnic
      minority families.

PMID- 16799702
TI  - Remyelination of spinal cord axons by olfactory ensheathing cells and Schwann
      cells derived from a transgenic rat expressing alkaline phosphatase marker gene.
AB  - Transplantation of cell suspensions containing olfactory ensheathing cells (OECs)
      has been reported to remyelinate demyelinated axons in the spinal cord with a
      Schwann cell (SC)-like pattern of myelination. However, questions have been
      raised recently as to whether OECs can form SC-like myelin. To address this issue
      we prepared SCs and OECs from transgenic rats in which a marker gene, human
      placental alkaline phosphatase (hPAP), is linked to the ubiquitously active
      promoter of the R26 gene. SCs were prepared from the sciatic nerve and OECs from
      the outer nerve-fiber layer of the olfactory bulb. Positive S100 and p75
      immunostaining indicated that >95% of cells in culture displayed either SC or OEC
      phenotypes. Suspensions of either SCs or OECs were transplanted into an X
      irradiation/ethidium bromide demyelinating lesion in the spinal cord. We observed
      extensive SC-like remyelination following either SC or OEC transplantation 3
      weeks after injection of the cells. Alkaline phosphatase (ALP) chromagen reaction
      product was associated clearly with the myelin-forming cells. Thus, cell
      suspensions that are enriched in either SCs or OECs result in peripheral-like
      myelin when transplanted in vivo.

PMID- 16799703
TI  - Enantioselective Radical Reactions. Formation of Chiral Quaternary Centers.
AB  - A novel addition/trapping radical reaction to establish all carbon chiral
      quaternary centers has been developed.

PMID- 16799704
TI  - Enantioselective radical reactions. Evaluation of nitrogen protecting groups in
      the synthesis of beta-amino acids.
AB  - We have investigated the effect of nitrogen protecting groups in radical addition
      trapping experiments leading to beta(2)-amino acids. Of the three N-protecting
      groups examined, the phthalimido group was optimal with respect to both yields
      and enantioselectivity. Additionally, radical additions to more complex acrylates
      were also investigated, which provided access to functionalized beta(2)-amino
      acids in modest selectivity.

PMID- 16799705
TI  - Leptin--from regulation of fat metabolism to stimulation of breast cancer growth.
AB  - Leptin restricts intake of calories as a satiety hormone. It probably stimulates
      neoplastic proliferation in breast cancer, too. Growth of malignant cells could
      be regulated by various leptin-induced second messengers like STAT3 (signal
      transducers and activators of transcription 3), AP-1 (transcription activator
      protein 1), MAPK (mitogen-activated protein kinase) and ERKs (extracellular
      signal-regulated kinases). They seem to be involved in aromatase expression,
      generation of estrogens and activation of estrogen receptor alpha (ERalpha) in
      malignant breast epithelium. Leptin may maintain resistance to antiestrogen
      therapy. Namely, it increased activation of estrogen receptors, therefore, it was
      suspected to reduce or even overcome the inhibitory effect of tamoxifen on breast
      cell proliferation. Although several valuable reviews have been focused on the
      role of leptin in breast cancer, the status of knowledge in this field changes
      quickly and our insight should be continuously revised. In this summary, we
      provide refreshed interpretation of intensively reported scientific queries of
      the topic.

PMID- 16799706
TI  - E-cadherin expression in transitional cell carcinomas.
AB  - The authors analyzed the expression of E-cadherin, one of the most important cell
      adhesion molecules, on histological slides of tumors of bladder cancer patients.
      The aim of the study was to see whether there is any association between E
      cadherin expression and tumor grade, stage, age and gender of the patients,
      number of recurrences, or overall survival. The samples were examined in 51
      primary bladder transitional cell carcinomas (TCC) of 50 patients, resected by
      transurethral resection (TUR) between January 1, 1996 and January 1, 1997.
      Immunoreactions were performed with monoclonal anti-human E-cadherin antibody.
      Forty of the fifty patients could be clinically followed. The analysis of the
      results on these forty patients was performed by contingency analysis and
      significance was assessed by chi2 test. No significant association between E
      cadherin expression and tumor grade, stage, age or gender of the patients, the
      number of recurrences, or overall survival could be seen.

PMID- 16799707
TI  - HLA class II polymorphism: protective or risk factors to breast cancer in
      Tunisia?
AB  - HLA system plays a key role in the tumor cells' escape from immune surveillance.
      Herein is the first report on the correlation of the susceptibility to breast
      cancer with HLA class II markers in Tunisia. Molecular typing of HLA-DRB1 and 
      DQB1 loci was undertaken for 70 Tunisian female patients. Comparison of allele
      and haplotype distribution between patients and 70 female control subjects
      reveals a negative association between HLADRB1* 07-DQB1*02 and the incidence of
      breast cancer in the Tunisian population.

PMID- 16799708
TI  - Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan.
AB  - The management and prognosis of breast cancer nowadays require the evaluation of
      Estrogen (ER), Progesterone Receptors (PR) and HER2/neu. Ethnic variation in the
      expression of these receptors is well documented. The aim of this study is to
      determine the prevalence of ER, PR and HER2/neu among Jordanian women with breast
      cancer of ductal and lobular types. A retrospective analysis was performed on 267
      cases of breast cancer referred for treatment at King Hussein Cancer Center,
      Jordan between the period of June 2003 and June 2004. Standard immune stains were
      used for evaluation of hormone receptors and HER2/neu. In addition, evaluation of
      HER2/neu was done by FISH in selected cases. Of these 267 cases, 240 (89.9%) were
      ductal carcinomas of various histological grades, 122 (50.8%) of which were ER
      positive, 138 (57.5%) PRpositive and 42 (17.5%) HER2/neu-positive. Twentytwo
      (8.2%) of all cases were lobular carcinomas, 15 (68%) of which were ER-positive,
      20 (90.9%) PRpositive and 3 (13.6%) HER2/neu-positive. Five (1.9%) of the total
      cases were of mixed lobular and ductal types, 4 (80%) of which were ER-positive,
      3 (60%) PR-positive and none were positive for HER2/neu. The prevalence of
      hormone receptor positivity in breast cancer of Jordanian women is lower than
      that of the western populations and close to other populations such as the
      Chinese and the minor ethnic groups of Northern America (African Americans).

PMID- 16799709
TI  - Immunohistochemical expression of EGFR and p-EGFR in oral squamous cell
      carcinomas.
AB  - Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB
      family, which is expressed or highly expressed in a variety of solid tumors,
      including oral cancers. High EGFR expression has been correlated with tumor size,
      metastasis and survival. In recent years, EGFR has been considered a promising
      target for monoclonal antibody therapy. A total of 52 patients with oral squamous
      cell carcinoma (OSCC) were selected for EGFR and phosphorylated EGFR (p-EGFR)
      detection. Immunohistochemical staining was performed to evaluate EGFR and p-EGFR
      expression. Positive EGFR and p-EGFR staining was present in 92.3% (48/52) and
      98.0% (51/52) of all cases, respectively. High EGFR and p-EGFR expression was
      present in 63.4% (33/52) and 69.2% (36/52) of all cases, respectively. EGFR and p
      EGFR expression did not correlate with the clinical factors tumor stage, regional
      lymph node metastasis, or distant metastasis. However, a statistically
      significant correlation was identified between high EGFR expression and the
      pathologic factor tumor invasion. As a conclusion, the majority of OSCCs highly
      express EGFR and p-EGFR, indicating the importance of studying the efficacy of
      anticancer therapy targeting these signal factors.

PMID- 16799710
TI  - Collaborative/active participation per se does not decrease anxiety in breast
      cancer.
AB  - The information needs of breast cancer patients on their disease, its treatment,
      the prognosis, and their attitude to decision-making concerning treatment were
      assessed. One hundred and fifty early and 45 metastatic breast cancer patients
      were recruited into the study. The amount of information and role in the
      treatment decision-making process preferred by the patient were independently
      estimated by the patient and the oncologist, using questionnaires. Information
      was provided in accordance with the wishes of the patient as perceived by the
      physician. Test of anxiety was performed before, and one week after the
      consultation. Most of the patients claimed to anticipate the provision of
      extensive information and an active role in the decision-making, but real
      interest during the consultation was found less frequently. The post-consultation
      anxiety test revealed a significant decrease in situational anxiety; this was not
      related to the patient's information needs or her attitude to the decision-making
      concerning treatment. Our study demonstrates that a significant decrease in
      anxiety may be achieved via a consultation tailored to the needs of the patient.
      Loading the patient with information and involvement in the decision regarding
      therapy as much as the patient seems comfortable with lowers distress.

PMID- 16799711
TI  - Pleomorphic rhabdomyosarcoma of the uterus in a postmenopausal patient.
AB  - Pure rhabdomyosarcomas occurring in the adult uterus are very rare, with poor
      prognosis. We present a case of a 67-year-old woman with postmenopausal vaginal
      bleeding caused by pleomorphic rhabdomyosarcoma of the uterus, treated with
      hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy
      and partial sigmoidectomy. Postoperative chemotherapy (Doxorubicin) was given
      according to protocol. Follow-up examinations one year after surgery revealed no
      abnormalities or tumor recurrence. The rarity of this histological entity makes
      the presented case worthy of publication.

PMID- 16799712
TI  - The nested variant of urothelial carcinoma: an aggressive tumor closely
      simulating benign lesions.
AB  - The "nested" variant is a rare form of urothelial carcinoma and its biologic
      behavior is highly aggressive. Herein two new cases of nested variant of
      urothelial carcinoma with immunohistochemical examination are presented. In one
      of the cases, the tumor extended through the bladder wall into the perivesicular
      soft tissue, prostatic urethra and left vesicula seminalis, and metastasized to
      obturator lymph nodes. In the other case, invasion of muscular layer was observed
      and three recurrences were developed during a follow-up period of 23 months. Both
      tumors of our study demonstrated high p53 and Ki-67 indices, supporting the
      aggressive nature of such tumors.

PMID- 16799713
TI  - Krukenberg tumor in pregnancy. The lethal outcome.
AB  - Krukenberg tumor refers to gastrointestinal cancer metastatic to the ovaries and
      its prognosis is uniformly poor. This case report concerns a 38-year-old pregnant
      woman suffering from abdominal pain and iterative vomiting episodes. She
      presented with a large abdominopelvic tumor. Because of suspected ovarian
      torsion, we performed urgent surgery. At laparotomy, bilateral ovarian tumors,
      ascites and gastric cancer located at the cardia and the lesser curvature
      invading the serosa were identified. We performed right ovariectomy, resection of
      the left ovary, and gastric biopsy. Histological examination of the specimen
      yielded diagnosis of Krukenberg tumor. Ten days later the patient underwent an
      elective Cesarean section in the 25th gestational week because of fetal asphyxia
      and very poor maternal life prognosis. We performed Cesarean delivery and
      extracted a vital female newborn of 31 cm, 600 g, Ap score 3, with virilization.
      Few days later the baby died at the intensive care unit. Two weeks later the
      mother died because of pulmonary failure.

PMID- 16799714
TI  - Fibrocartilaginous dysplasia (fibrous dysplasia with extensive cartilaginous
      differentiation).
AB  - Fibrocartilaginous dysplasia is a variant of fibrous dysplasia in which extensive
      cartilaginous differentiation is identified. The amount of cartilage varies from
      case to case, however, no percentage has been proposed to consider this
      diagnosis. We present a 6-year-old girl with a two-year history of hip pain.
      Initial imaging studies of the right femur revealed a lucent lesion of the
      proximal shaft that extended into the femoral neck with ill-defined borders but
      well maintained cortex. Computed tomography scan demonstrated increased density
      of the medullary cavity but the cortex appeared intact. Curettage of the lesion
      was performed and fragments with cartilaginous appearance were obtained, weighing
      45 g in total. Microscopically, the tumor revealed a cartilaginous (60%) and a
      fibro-osseous (40%) component; the former had increased cellularity and some
      chondrocytes displayed moderate atypia and binucleation, while the latter showed
      features of fibrous dysplasia. Areas of endochondral ossification and
      calcification were also identified. After five years of surgery this child is
      well and without evidence of recurrence. We discuss the differential diagnosis of
      this variant of fibrous dysplasia in the pediatric group.

PMID- 16799715
TI  - Distal myopathy with rimmed vacuoles and cerebellar atrophy.
AB  - Distal myopathies constitute a clinically and pathologically heterogeneous group
      of genetically determined neuromuscular disorders, where the distal muscles of
      the upper or lower limbs are affected. The disease of a 41-year-old male patient
      started with gait disturbances, when he was 25. The progression was slow, but
      after 16 years he became seriously disabled. Neurological examination showed
      moderate to severe weakness in distal muscles of all extremities, marked
      cerebellar sign and steppage gait. Muscle biopsy resulted in myopathic changes
      with rimmed vacuoles. Brain MRI scan showed cerebellar atrophy. This case
      demonstrates a rare association of distal myopathy and cerebellar atrophy.

PMID- 16799717
TI  - Facing the health worker crisis in developing countries: a call for global
      solidarity.

PMID- 16799716
TI  - Cancer gene therapy: combination with radiation therapy and the role of bystander
      cell killing in the anti-tumor effect.
AB  - Current anti-cancer modalities such as surgery, chemo- and radiation therapies
      have only limited success in cancer treatment. Gene therapy is a promising new
      tool to improve outcomes. In this review, first we summarize the various
      strategies to kill tumor cells, and then focus on the bystander effect of gene
      therapy. A variety of strategies, such as gene-directed enzyme pro-drug therapy,
      activation of an anti-tumor immune attack, application of replication-competent
      and oncolytic viral vectors, tumor-specific as well as radiation- and
      hypoxiainduced gene expression, might be applied to target tumor cells. We put
      special emphasis on the combination of these approaches with local tumor
      irradiation. Using the available vector systems, only a small portion of cancer
      cells contains the therapeutic genes under clinical situations. However, cells
      directly targeted by gene therapy will transfer death signals to neighboring
      cancer cells. This bystander cell killing improves the efficiency of cancer gene
      therapy. Death signals are delivered by cell-to-cell communication through gap
      junction intercellular contacts, release of toxic metabolites into the
      neighborhood or to larger distances, phagocytosis of apoptotic bodies, and the
      activation of the immune system. Bystander cell killing can be enhanced by the
      introduction of gap junction proteins into cells, by further activating the
      immune system with immune-stimulatory molecules, or by introducing genes that
      help the transfer of cytotoxic genes and/or metabolites into bystander cells. In
      conclusion, although bystander cell killing can improve therapeutic effects,
      there should be additional developments in cancer gene therapy for a more
      efficient clinical application.

PMID- 16799718
TI  - Safe in their hands? Engaging private providers in the quest for public health
      goals.

PMID- 16799719
TI  - Tuberculosis care and control.

PMID- 16799720
TI  - Giving patients better access to trial information.

PMID- 16799721
TI  - No delayed disclosure for registration of clinical trials.

PMID- 16799723
TI  - In search of a sustainable philanthropy.

PMID- 16799724
TI  - Global public health sees new crop of leaders.

PMID- 16799725
TI  - Making technology serve public health.

PMID- 16799727
TI  - Cost and cost-effectiveness of PPM-DOTS for tuberculosis control: evidence from
      India.
AB  - OBJECTIVE: To assess the cost and cost-effectiveness of the Public-Private Mix
      DOTS (PPM-DOTS) strategy for tuberculosis (TB) control in India. METHODS: We
      collected data on the costs and effects of pilot PPM-DOTS projects in Delhi and
      Hyderabad using documentary data and interviews. The cost of PPM-DOTS was
      compared with public sector DOTS (i.e. DOTS delivered through public sector
      facilities only) and non-DOTS treatment in the private sector. Costs for 2002 in
      US$ were assessed for the public sector, private practitioners, and
      patients/attendants. Effectiveness was measured as the number of cases
      successfully treated. FINDINGS: The average cost per patient treated was US$ 111
      123 for PPM-DOTS and public sector DOTS, and US$ 111-172 for non-DOTS treatment
      in the private sector. From the public sector's perspective, the cost per patient
      treated was lower in PPM-DOTS projects than in public sector DOTS programmes (US$
      24-33 versus US$ 63). DOTS implementation in either the public or private sectors
      improved treatment outcomes and substantially lowered costs incurred by patients
      and their attendants, compared to non-DOTS treatment in the private sector (US$
      50-60 for DOTS compared to over US$ 100 for non-DOTS). The average cost
      effectiveness of PPM-DOTS and public sector DOTS was similar, at US$ 120-140 per
      patient successfully treated, compared to US$ 218-338 for non-DOTS private sector
      treatment. Incremental cost-effectiveness analysis showed that PPM-DOTS can
      improve effectiveness while also lowering costs. CONCLUSION: PPM-DOTS can be an
      affordable and cost-effective approach to improving TB control in India, and can
      substantially lower the economic burden of TB for patients.

PMID- 16799728
TI  - Cross-sectional associations between intensity of animal and human infection with
      Schistosoma japonicum in Western Samar province, Philippines.
AB  - OBJECTIVE: To estimate the association between the intensity of animal infection
      with Schistosoma japonicum and human infection in Western Samar province, the
      Philippines. METHODS: We conducted an observational cross-sectional study of 1425
      households in 50 villages. Stool samples were collected on each of 1-3 days from
      5623 humans, 1275 cats, 1189 dogs, 1899 pigs, 663 rats and 873 water buffalo.
      Intensity of infection with S. japonicum was measured by the number of eggs per
      gram (EPG). Egg counts were done using the Kato-Katz method. We used a Bayesian
      hierarchical cumulative logit model, with adjustments for age, sex, occupation
      and measurement error. FINDINGS: The adjusted proportions of humans lightly
      infected (classified as 1-100 EPG) was 17.7% (95% Bayesian credible interval =
      15.3-20.2%); the proportion classified as at least moderately infected (>100 EPG)
      was 3.2% (2.2-4.6%). The crude parasitological results for animals indicated that
      37 cats (2.9%), 228 dogs (19.2%), 39 pigs (2.1%), 199 rats (30.0%) and 28 water
      buffalo (3.2%) were infected. In univariate analyses the odds ratios
      corresponding to a unit increase in the mean number of EPG at the village-level
      in dogs was 1.05 (1.01-1.09), in cats 1.35 (1.02-1.78), in pigs 1.16 (0.24- 5.18)
      and in rats 1.00 (1.00-1.01). Mean EPG values in cats, dogs, pigs and rats were
      correlated with one another. This confounding made interpreting the odds ratios
      difficult, but the odds ratios for dogs and cats were more consistent.
      CONCLUSION: S. japonicum is endemic in areas of the Philippines despite
      implementation of control programmes. This may be due to the association of
      infections in dogs and cats with human infections. Infection control in dogs and
      cats is challenging, and there is a need to develop new methods to control
      transmission across all species.

PMID- 16799729
TI  - Multicentre study of acute alcohol use and non-fatal injuries: data from the WHO
      collaborative study on alcohol and injuries.
AB  - OBJECTIVES: To study the risk of non-fatal injury at low levels and moderate
      levels of alcohol consumption as well as the differences in risk across modes of
      injury and differences among alcoholics. METHODS: Data are from patients aged 18
      years and older collected in 2001-02 by the WHO collaborative study on alcohol
      and injuries from 10 emergency departments around the world (n = 4320). We used a
      case-crossover method to compare the use of alcohol during the 6 hours prior to
      the injury with the use of alcohol during same day of the week in the previous
      week. FINDINGS: The risk of injury increased with consumption of a single drink
      (odds ratio (OR) = 3.3; 95% confidence interval = 1.9-5.7), and there was a 10
      fold increase for participants who had consumed six or more drinks during the
      previous 6 hours. Participants who had sustained intentional injuries were at a
      higher risk than participants who had sustained unintentional injuries. Patients
      who had no symptoms of alcohol dependence had a higher OR. CONCLUSION: Since low
      levels of drinking were associated with an increased risk of sustaining a non
      fatal injury, and patients who are not dependent on alcohol may be at higher risk
      of becoming injured, comprehensive strategies for reducing harm should be
      implemented for all drinkers seen in emergency departments.

PMID- 16799730
TI  - Methods for establishing a surveillance system for cardiovascular diseases in
      Indian industrial populations.
AB  - OBJECTIVE: To establish a surveillance network for cardiovascular diseases (CVD)
      risk factors in industrial settings and estimate the risk factor burden using
      standardized tools. METHODS: We conducted a baseline cross-sectional survey (as
      part of a CVD surveillance programme) of industrial populations from 10 companies
      across India, situated in close proximity to medical colleges that served as
      study centres. The study subjects were employees (selected by age and sex
      stratified random sampling) and their family members. Information on behavioural,
      clinical and biochemical determinants was obtained through standardized methods
      (questionnaires, clinical measurements and biochemical analysis). Data collation
      and analyses were done at the national coordinating centre. FINDINGS: We report
      the prevalence of CVD risk factors among individuals aged 20-69 years (n = 19 973
      for the questionnaire survey, n = 10 442 for biochemical investigations); mean
      age was 40 years. The overall prevalence of most risk factors was high, with
      50.9% of men and 51.9% of women being overweight, central obesity was observed
      among 30.9% of men and 32.8% of women, and 40.2% of men and 14.9% of women
      reported current tobacco use. Self-reported prevalence of diabetes (5.3%) and
      hypertension (10.9%) was lower than when measured clinically and biochemically
      (10.1% and 27.7%, respectively). There was marked heterogeneity in the prevalence
      of risk factors among the study centres. CONCLUSION: There is a high burden of
      CVD risk factors among industrial populations across India. The surveillance
      system can be used as a model for replication in India as well as other
      developing countries.

PMID- 16799731
TI  - Health transitions in sub-Saharan Africa: overview of mortality trends in
      children under 5 years old (1950-2000).
AB  - OBJECTIVE: To reconstruct and analyse mortality trends in children younger than 5
      years in sub-Saharan Africa between 1950 and 2000. METHODS: We selected 66
      Demographic and Health Surveys and World Fertility Surveys from 32 African
      countries for analysis. Death rates were calculated by yearly periods for each
      survey. When several surveys were available for the same country, overlapping
      years were combined. Country-specific time series were analysed to identify
      periods of monotonic trends, whether declining, steady or increasing. We tested
      changes in trends using a linear logistic model. FINDINGS: A quarter of the
      countries studied had monotonic declining mortality trends: i.e. a smooth health
      transition. Another quarter had long-term declines with some minor rises over
      short periods of time. Eight countries had periods of major increases in
      mortality due to political or economic crises, and in seven countries mortality
      stopped declining for several years. In eight other countries mortality has risen
      in recent years as a result of paediatric AIDS. Reconstructed levels and trends
      were compared with other estimates made by international organizations, usually
      based on indirect methods. CONCLUSION: Overall, major progress in child survival
      was achieved in sub-Saharan Africa during the second half of the twentieth
      century. However, transition has occurred more slowly than expected, with an
      average decline of 1.8% per year. Additionally, transition was chaotic in many
      countries. The main causes of mortality increase were political instability,
      serious economic downturns, and emerging diseases.

PMID- 16799732
TI  - Turning liabilities into resources: informal village doctors and tuberculosis
      control in Bangladesh.
AB  - In 1998, the Damien Foundation Bangladesh invited semi-qualified, private "gram
      dakter" (Bangla for "village doctors") to participate in tuberculosis (TB)
      programmes in a population of 26 million people in rural Bangladesh. The
      organization trained 12 525 village doctors to not only refer suspected TB cases
      for free diagnosis but also to provide directly observed treatment (DOT) free of
      charge. Source of referral and place of DOT was recorded as part of the
      standardized TB recording and reporting system, which enabled us to quantify the
      contribution of village doctors to case detection rates and also allowed
      disaggregated cohort analysis of treatment outcome. During 2002 and 2003, 11% of
      all TB cases with positive sputum smears in the study area had been referred by
      village doctors; the rate of positive tests in patients referred by village
      doctors was 14.4%. 18 792 patients received DOT from village doctors, accounting
      for between 20% and 45% of patients on treatment during the 1998-2003 period. The
      treatment success rate was about 90% throughout the period. Urine samples taken
      during random checks of treatment compliance were positive for isoniazid in 98%
      of patients treated by village doctors. Within the framework of Public-Private
      Mix DOTS, services provided by semi-qualified private health care providers are a
      feasible and effective way to improve access to affordable high quality TB
      treatment in poor rural populations. The large informal health workforce that
      exists in resource poor countries can be used to achieve public health goals.
      Involvement of village doctors in TB control has now become national policy in
      Bangladesh.

PMID- 16799733
TI  - Is the current public health message on UV exposure correct?
AB  - Current sun safety messages stress the importance of sun protection in avoiding
      the consequences of excessive exposure to ultraviolet radiation (UVR), such as
      skin cancers, cataracts and other eye diseases, and viral infections caused by UV
      induced immunosuppression. However, adequate exposure to UVR has an important
      role in human health, primarily through UV-induced production of vitamin D, a
      hormone essential to bone health. Vitamin D insufficiency may be associated with
      increased risks of some cancers, autoimmune diseases and mental health disorders
      such as schizophrenia. Here, we review the evolution of current sun exposure
      practices and sun-safe messages and consider not only the benefits, but also the
      detrimental effects that such messages may have. UVR-induced vitamin D production
      can be inhibited by factors such as deep skin pigmentation, indoor lifestyles,
      older age, sun avoidance behaviours and clothing habits that limit skin exposure,
      with deleterious consequences for health. There is some early evidence that sun
      safe messages are beginning to cause a decrease in skin cancer rates in young
      people. After the widespread promotion of sun safety, it may now be appropriate
      to refine public health messages to take better account of variations between
      groups and their susceptibility to the dangers and benefits of sun exposure.

PMID- 16799734
TI  - The suicide epidemic in Japan and strategies of depression screening for its
      prevention.

PMID- 16799735
TI  - Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis.

PMID- 16799736
TI  - [The carcinogenic effects of tobacco. Monatsschrift fur Krebsbekampfung Vol. 8,
      Issue 5, 1940].

PMID- 16799737
TI  - Evidence-based reproductive health care.

PMID- 16799738
TI  - Neutron capture radiography: a technique for isotopic labelling and analytical
      imaging with a few stable isotopes.
AB  - NCR (neutron capture radiography) may be used successfully for the imaging of one
      of the stable isotopes of a few chemical elements (especially 6Li and 10B,
      possibly also 14N, 17O, and others) and for labelling experiments using these
      stable isotopes. Other physical techniques compete with NCR. However, NCR can
      remain extremely useful in a certain number of cases, because it is usually more
      easily done and is less expensive than the other techniques.

PMID- 16799739
TI  - Correlation between number of retrieved oocytes and pregnancy rate after in vitro
      fertilization/intracytoplasmic sperm infection.
AB  - The implementation of safe and maximally effective ovarian stimulation is a major
      aim for in vitro fertilization (IVF) teams. The goal of controlled ovarian
      hyperstimulation (COH) is to supply enough oocytes with normal maturation to
      insure the consequent biological procedures. A variety of different stimulation
      protocols have been suggested and an individual selection of the correct
      stimulation protocol is mandatory. The aim of the present study is to evaluate
      the correlation between number of retrieved oocytes and clinical pregnancy rate
      (CPR) after IVF or intracytoplasmic sperm injection (ICSI) procedures. We
      reviewed 1017 cycles in a total of 975 patients. The study results clearly
      demonstrate that the aspiration of less than 5 oocytes significantly reduced
      pregnancy rate. The aspiration of a large number of oocytes (>15) does not lead
      to an increase of the treatment effect and, at the same time, increases the risk
      of ovarian hyperstimulation syndrome. The major goal is to obtain 5-15 oocytes as
      a "gold standard", connected to optimal pregnancy rate after assisted
      reproduction (ART).

PMID- 16799740
TI  - Ultraviolet fluorescence imaging of fingerprints.
AB  - We studied fluorescence imaging of fingerprints on a high-grade white paper in
      the deep ultraviolet (UV) region with a nanosecond-pulsed Nd-YAG laser system
      that consists of a tunable laser and a cooled CCD camera. Clear fluorescence
      images were obtained by time-resolved imaging with a 255- to 425-nm band-pass
      filter, which cuts off strong fluorescence of papers. Although fluorescence can
      be imaged with any excitation wavelength between 220 and 290 nm, 230 and 280 nm
      are the best in terms of image quality. However, the damage due to laser
      illumination was smaller for 266-nm excitation than 230- or 280-nm excitation.
      Absorption images of latent fingerprints on a high-grade white paper are also
      obtained with our imaging system using 215- to 280-nm laser light. Shorter
      wavelengths produce better images and the best image was obtained with 215 nm.
      Absorption images are also degraded slightly by laser illumination, but their
      damage is smaller than that of fluorescence images.

PMID- 16799741
TI  - Alcohol and suicide: neurobiological and clinical aspects.
AB  - Alcohol, primarily in the form of ethyl alcohol (ethanol), has occupied an
      important place in the history of humankind for at least 8,000 years. In most
      Western societies, at least 90% of people consume alcohol at some time during
      their lives, and 30% or more of drinkers develop alcohol-related problems. Severe
      alcohol-related life impairment, alcohol dependence (alcoholism), is observed at
      some time during their lives in about 10% of men and 3-5% of women. An additional
      5-10% of each sex develops persistent, but less intense, problems that are
      diagnosed as alcohol abuse. It this review, neurobiological aspects of suicidal
      behavior in alcoholism is discussed. In individuals with comorbid depression and
      alcoholism, greater serotonergic impairment may be associated with higher risk of
      completed suicide. Dopaminergic dysfunction may play an important role in the
      pathophysiology of suicidal behavior in alcoholism. Brain damage and
      neurobehavioral deficits are associated with alcohol use disorders and may
      contribute to suicidal behavior in persons with alcohol dependence or abuse.
      Aggression/impulsivity and alcoholism severity affect risk for suicide among
      individuals with alcoholism. Major depressive episodes and stressful life events
      particularly, partner-relationship disruptions, may precipitate suicidal behavior
      in individuals with alcohol use disorders. Alcohol misuse and psychosocial
      adversity can combine to increase stress on the person, and, thereby,
      potentially, increase the risk for suicidal behavior. The management of suicidal
      patients with alcohol use disorders is also discussed. It is to be hoped that the
      efforts of clinicians will reduce morbidity and mortality associated with alcohol
      misuse.

PMID- 16799742
TI  - Individual and environmental impacts on sexual health of Caribbean youth.
AB  - Individual health risk behaviors among Caribbean youth account for the majority
      of adolescent morbidity and mortality in that area. This study explores the
      associations between individual factors, socioenvironmental factors, and sexual
      health-related behaviors in Caribbean youth. Data from the 1995 Caribbean Youth
      Health Survey, a nine-country, cross-sectional study completed by 15,695 in
      school youth 10-18 years of age were analyzed. One-third of the sample (n =
      5,060) reporting sexual activity was analyzed. This study examined age at first
      sexual intercourse, number of sexual partners, history of pregnancy, and condom
      use. The predictor variables were rage, depressed mood, expectation of early
      death, self-reported school performance, parental mental health or substance
      abuse problems, and family connectedness. Bi- and multivariate analyses were done
      separately for males and females, controlling for age, to examine associations
      between individual and socioenvironmental factors and sexual health behaviors. In
      the multivariate model, there were associations between rage, abuse, family
      mental health and substance use, anticipation of early death, and many of the
      outcome variables in males and females. Family connectedness and positive self
      reported school status were correlated with greater condom use at last
      intercourse in males. Family connectedness was correlated with older age at first
      sexual intercourse. Depressed mood was not correlated with any of the outcome
      variables. The findings of the study demonstrate an association between
      individual and socioenvironmental factors and sexual health behaviors in the
      lives of Caribbean youth. Strong associations between rage and physical/sexual
      abuse and risky sexual behaviors are of notable concern.

PMID- 16799743
TI  - The astronomical pulse of global extinction events.
AB  - The linkage between astronomical cycles and the periodicity of mass extinctions
      is reviewed and discussed. In particular, the apparent 26 million year cycle of
      global extinctions may be related to the motion of the solar system around the
      galaxy, especially perpendicular to the galactic plane. The potential relevance
      of Milankovitch cycles is also explored in the light of current evidence for the
      possible causes of extinction events over a geological timescale.

PMID- 16799744
TI  - A consensus document on bowel preparation before colonoscopy: prepared by a Task
      Force from the American Society of Colon and Rectal Surgeons (ASCRS), the
      American Society for Gastrointestinal Endoscopy (ASGE), and the Society of
      American Gastrointestinal and Endoscopic Surgeons (SAGES).

PMID- 16799745
TI  - Violence in psychiatric units: a 7-year Italian study of persistently assaultive
      patients.
AB  - BACKGROUND: The problem of violence and aggressive behaviour among patients with
      psychiatric disorders need careful assessment to improve the quality of
      psychiatric care. The aim of this paper is to describe the characteristics of
      repeated episodes of violence among patients admitted to an Italian psychiatric
      ward. METHODS: All violent behaviours, which occurred in a 15-bed psychiatric
      inpatient unit over a 7-year period, were assessed by using the Staff Observation
      Aggression scale (SOAS). RESULTS: Of a total of 3.507 admissions, 409 aggressive
      episodes were recorded by 160 patients (rate per admission 11.6%). A total of 65
      patients exhibited two or more episodes and 95 patients showed a single episode.
      Repeatedly violent patients had a higher length of stay in the unit, a higher
      number of previous admissions and a higher number of previous violent episodes.
      No difference was found in terms of psychiatric diagnosis, socio-demographic
      variables, type of admission (voluntary versus involuntary), ward overcrowding
      and characteristics of violent episodes (means, aims and consequence).
      CONCLUSIONS: In spite of the low prevalence of violent incidents among Italian
      psychiatric inpatients, careful monitoring of clinical variables associated with
      repeated violent episodes may help physicians recognise and prevent violence
      episodes among acute psychiatric inpatients.

PMID- 16799747
TI  - Comparison of habitat quality and diet of Colobus vellerosus in forest fragments
      in Ghana.
AB  - The forest fragments surrounding the Boabeng-Fiema Monkey Sanctuary (BFMS) in
      central Ghana shelter small populations of Colobus vellerosus. Little is known
      about these populations or the ability of the fragments to support them, despite
      the fact that these fragments represent potentially important habitat for the
      colobus in this region. We compared the diet of three groups of C. vellerosus in
      the fragments to two groups in BFMS. We also examined the differences in plant
      species composition and food abundance among fragments. The study took place from
      June to November 2003. Dietary data were collected using scan sampling. Plant
      species composition and food abundance were evaluated using tree plots and large
      tree surveys. As in BFMS groups, leaves constituted the highest proportion of the
      diet of fragment groups, yet the colobus in fragments fed on more lianas than did
      those in BFMS. Over 50% of all species observed eaten by colobus in the fragments
      were not consumed in BFMS groups during the same season. Food abundance was
      similar between fragments and BFMS, although species composition differed. There
      was no relationship between the density of colobus and the density of food trees
      or percentage of food species, suggesting that other factors may be influencing
      the number of colobus present. This study highlights the broad dietary range of
      C. vellerosus, which may be a factor allowing its survival in these fragments.

PMID- 16799746
TI  - Polyphasic analysis of Thermus isolates from geothermal areas in Iceland.
AB  - Genetic relationships and diversity of 101 Thermus isolates from different
      geothermal regions in Iceland were investigated by using multilocus enzyme
      electrophoresis (MLEE) and small subunit ribosomal rRNA (SSU rRNA) sequence
      analysis. Ten polymorphic enzymes were used and seven distinct and genetically
      highly divergent lineages of Thermus were observed. Six of seven lineages could
      be assigned to species whose names have been validated. The most diverse lineage
      was Thermus scotoductus. In contrast to the other lineages, this lineage was
      divided into very distinct genetic sublineages that may represent subspecies with
      different habitat preferences. The least diverse lineage was Thermus brockianus.
      Phenotypic and physiological analysis was carried out on a subset of the
      isolates. No relationship was found between growth on specific single carbon
      source to the grouping obtained by the isoenzyme analysis. The response to
      various salts was distinguishing in a few cases. No relationship was found
      between temperature at the isolation site and the different lineages, but pH
      indicated a relation to specific lineages.

PMID- 16799748
TI  - Application of a PDMS microstencil as a replaceable insulator toward a single-use
      planar microelectrode array.
AB  - Here we present a novel idea for a replaceable insulator, and thus advance toward
      the goal of a single-use planar microelectrode array (MEA) for the study of
      electrogenic tissues. The concept of a replaceable insulator is motivated by
      insulator degradation after repeated usage of an MEA. Instead of fabricating a
      more durable insulator for repeated MEA usage, we propose replacing the insulator
      and effectively producing a fresh MEA for each experiment. We chose a
      polydimethylsiloxane (PDMS) microstencil as a candidate for the replaceable
      insulator as it is biocompatible, shows reversible adhesion to surfaces, and can
      be easily and controllably fabricated. As a proof-of-concept, we demonstrate two
      applications using microstencils: the rejuvenation of an old MEA and the
      fabrication of a single-use MEA. These MEAs were tested with dissociated neural
      cell cultures and neural recordings were performed at 14 days in vitro.
      Inexpensive and quick supply of insulators with micrometer-sized holes provides a
      way of constructing an MEA that can be treated as a disposable component in high
      throughput cell-based biosensor applications.

PMID- 16799749
TI  - DNA counterion current and saturation examined by a MEMS-based solid state
      nanopore sensor.
AB  - Reports of DNA translocation measurements have been increasing rapidly in recent
      years due to advancements in pore fabrication and these measurements continue to
      provide insight into the physics of DNA translocations through MEMS based solid
      state nanopores. Specifically, it has recently been demonstrated that in addition
      to typically observed current blockages, enhancements in current can also be
      measured under certain conditions. Here, we further demonstrate the power of
      these nanopores for examining single DNA molecules by measuring these ionic
      currents as a function of the applied electric field and show that the direction
      of the resulting current pulse can provide fundamental insight into the physics
      of condensed counterions and the dipole saturation in single DNA molecules.
      Expanding on earlier work by Manning and others, we propose a model of DNA
      counterion ionic current and saturation of this current based on our experimental
      results. The work can have broad impact in understanding DNA sensing, DNA
      delivery into cells, DNA conductivity, and molecular electronics.

PMID- 16799750
TI  - A low temperature bonding of quartz microfluidic chip for serum lipoproteins
      analysis.
AB  - A low-temperature bonding method for microfabrication of quartz microfluidic
      chips has been developed. The bonding process involved two steps: pre-bonding and
      post-annealing at low temperature. The bonding quality was evaluated by measuring
      the shear force at bonding interface and the electrical properties of the chips.
      Shear force of 5.66 MPa (566 N/cm(2)) was obtained in a bonded chip after a post
      annealing at 200 degrees C for 6 h. We owe the strong bonding strength to the
      formation of Si-O-Si bonds at the bonding interface during the post-annealing
      stage. The bonding procedures were not sensitive to surrounding and could be
      performed in a routine laboratory without clean room conditions. The performance
      of the fabricated microfluidic chips was tested by capillary zone electrophoresis
      (CZE) of serum lipoproteins with laser-induced fluorescence (LIF). The low
      density (LDL) and high-density (HDL) lipoproteins in the serum was separated
      completely by using tricine buffer with methylglucamine.

PMID- 16799751
TI  - Comparison between one midline cutaneous incision and two lateral incisions in
      the lumbar paraspinal approach by Wiltse: a cadaver study.
AB  - Wiltse has described in 1968 an intermuscular lumbar approach with two vertical
      incisions made at 30 mm each on both sides of the midline. Since 1988, Wiltse
      recommends to practice a single median incision because of aesthetic arguments
      and because it avoids potential difficulties in case of iterative surgery. In
      this paper, the goal of authors was to determine the advantages of two lateral
      incisions, particularly in term of cutaneous vascularization. This cadaveric
      study concerned ten specimens. Colored latex was injected into the lumbar
      segmentary arteries before taking a cutaneous flap. We calculated the mean of the
      number of vessels injected and cut on the midline, then all the 10 mm on both
      sides. The goal was to establish a cutaneous cartography, and to determine a zone
      of less vascular sacrifice. The lumbar skin was vascularized by an arteriolar
      network which spreads out from the midline. At 30 mm from the midline, the number
      of cut vessels is statistically less than in the others areas (P < 0.05). At this
      distance, the small arteries are superficial, fine, and the subcutaneous tissue
      appears poorly vascularized. The two lateral incisions have the advantage
      compared to a single median incision of being short, and of allowing a direct
      access to the muscular plan of cleavage without subcutaneous detachment, with a
      less pressure retraction. We think that an incision at 30 mm from spinous
      processes is less noxious for the skin because it is located at the border of two
      vascular territories, which depend of a median network for one, and a lateral
      network for the other. These incisions generate technical difficulties, however,
      when the approach is prolonged with the top of L2/L3, when a lateral and/or
      central canalar decompression is considered, and finally, in the event of
      iterative surgery.

PMID- 16799752
TI  - The pain associated with intraarticular hyaluronic acid injections for
      trapeziometacarpal osteoarthritis.
AB  - Trapeziometacarpal osteoarthritis predominantly affects middle-aged women. Most
      cases with rhizarthrosis can be managed successfully by conservative means. The
      purpose of this prospective study was to evaluate pain and tolerability of
      viscosupplementation therapy with hyaluronic acid (HA) for trapeziometacarpal
      osteoarthritis. Groups A and B consisted of eight patients each with Eaton stage
      3 or 4 rhizarthrosis, who underwent one cycle of three injections of (one per
      week) 0.3 cm3 sodium hyaluronate. The injections for group A were under
      fluoroscopy control, but fluoroscopy was not used in group B. Pain and
      tolerability of both groups A and B were measured and compared. The patients of
      the groups were also asked to evaluate the tolerability of the treatment. The
      results suggested that HA injection in the carpometacarpal joint is a tolerable
      procedure but the patients complained of pain and discomfort during the
      injections. The pain in group A was much greater than in group B.
      Viscosupplementation for the treatment of trapeziometacarpal osteoarthritis is a
      viable treatment option for stages 3 and 4 patients when they do not want to be
      operated on. It is a tolerable but not a painless procedure especially when it is
      done without fluoroscopy control. We recommend giving injections under
      fluoroscopy control.

PMID- 16799753
TI  - Impaired muscle strength is associated with fractures in hemodialysis patients.
AB  - INTRODUCTION: Fractures are extremely common among hemodialysis (HD) patients.
      METHODS: To assess if bone mineral density (BMD) and/or tests of muscle strength
      were associated with fractures, we studied 37 men and 15 women, 50 years and
      older, on HD for at least 1 year. We excluded subjects with prior renal
      transplants and women taking hormone replacement therapy. We inquired about low
      trauma fractures since starting dialysis. Subjects underwent BMD testing with a
      Lunar DPX-L densitometer. Tests of muscle strength included: timed up and go
      (TUG), 6-min walk, functional reach, and grip strength. Lateral and thoracic
      radiographs of the spine were obtained and reviewed for prevalent vertebral
      fractures. We used logistic regression to examine associations between fracture
      (prevalent vertebral, self-reported low trauma since starting dialysis and/or
      both) and BMD, and fracture and muscle-strength tests. Analyses were adjusted for
      age, weight, and gender. RESULTS: Mean age was 66+/-9.0 years, mean weight was
      72.9+/-15.2 kg, and most (35 of 52) participants were Caucasian. Average duration
      of dialysis was 40.2 (interquartile range: 24-61.2) months. The most common cause
      of renal failure was diabetes (16 subjects). There were no differences by gender
      or fracture. Of the 52 subjects, 27 had either a vertebral fracture or low trauma
      fracture. There was no association between fractures, hip or spine BMD, or grip
      strength. In contrast, greater functional reach [odds ratio (OR) per standard
      deviation (SD) increase: 0.29; 95% CI: 0.13-0.69), quicker TUG (OR per SD
      decrease: 0.14; 95% CI: 0.11-0.23), and a greater distance walked in 6 min (OR
      per SD increase: 0.10; 95% CI: 0.03-0.36) were all associated with a reduced risk
      of fracture. CONCLUSIONS: Impaired neuromuscular function is associated with
      fracture in hemodialysis patients.

PMID- 16799755
TI  - The direct and indirect costs of the chronic management of osteoporosis: a
      prospective follow-up of 3440 active subjects.
AB  - INTRODUCTION: The objective of this study was to estimate the direct and indirect
      costs attributable to osteoporosis (OP) from a societal and a payer's perspective
      among active subjects living in Belgium and employed in the public workforce.
      MATERIALS AND METHODS: A cohort of 3440 subjects employed by the Liege City
      Council was followed for 6 months. The City Council employees were invited to
      fill a monthly log of the data related to their utilization of health resources
      (contacts with health professionals, medical examinations, drug use,...) due to
      OP. Information on work disability (number of days of sick leave) and on informal
      care (number of days off work incurred by active subjects in helping relatives or
      friends suffering from OP) was also collected. RESULTS: Of those asked to
      participate in the study, 1,811 subjects filled in at least one questionnaire.
      The mean duration of follow-up was 3.46 months. Self-reported prevalence of OP at
      inclusion was 5.3%. OP subjects were significantly older (52.7+/-6.1 years) than
      normal subjects (45.5+/-9.8 years) (p<0.05) and included more women (85.3 vs.
      55.9%). Direct costs came to 44.6 euros per OP patient-month: 10.9 euros was
      spent on contact with health professionals, 19.0 euros on medical examinations,
      12.1 euros on drugs and 2.6 euros on hospitalizations. During this 6-month study,
      a total of 140 days of sick leave was recorded (mean: 0.4 per OP patient-month).
      From a payer's perspective, this loss in productivity yielded a mean cost of
      34.05 euros per OP patient-month. A mean number of days off work of 0.018 per
      active subject-month, attributable to informal care, was recorded. These days of
      inactivity represented, for the employer, a mean cost of 1.8 euros per active
      subject-month. CONCLUSION: The results of this survey of a large sample of active
      subjects confirm that OP-related expenditures, both for medical care and for loss
      of productivity, are significant.

PMID- 16799754
TI  - Comparative study of axial and femoral bone mineral density and parameters of
      mandibular bone quality in patients receiving dental implants.
AB  - INTRODUCTION: In view of the increase in the life expectancy of humans and in
      edentulism of the population above 50 years of age, in which the prevalence of
      osteoporosis is also higher, it is fundamental to better understand the effects
      of systemic bone mass loss on the healing process of dental implants and to
      determine the quality of the bone that surrounds them. The objective of the
      present study was to compare systemic osteoporosis (axial and femoral) and
      parameters of mandibular bone quality, and to evaluate osseointegration in
      postmenopausal women receiving dental implants. METHODS: The sample consisted of
      39 women aged 48-70 years, 19 with a densitometric diagnosis of osteoporosis in
      the lumbar spine and femoral neck and 20 controls with a normal densitometric
      diagnosis. Bone mineral density was measured in the patients and controls by dual
      energy X-ray absorptiometry. Eighty-two osseointegrated dental implants were
      placed in the mandible, 39 of them in the osteoporosis group and 43 in the
      control group. Mandibular bone quality was evaluated by classifying mandibular
      inferior cortical and trabecular bone on panoramic radiographs and by
      histomorphometric analysis of a mandibular bone biopsy. Osseointegration was
      analyzed after 9 months. RESULTS: No significant difference was observed between
      patients with osteoporosis and controls when comparing individuals with a normal
      cortex and those with a severely or moderately eroded cortex determined on
      panoramic radiographs. Histomorphometric analysis also revealed no difference in
      the parameters of bone formation or resorption between the two groups. Implant
      failure was observed in only one case. CONCLUSION: We conclude that there is no
      association between systemic osteoporosis (axial and femur) and parameters of
      poor mandibular bone quality. The loss of one implant (1.2%) is compatible with
      the literature and cannot be attributed to systemic osteoporosis.

PMID- 16799756
TI  - Agrobacterium-mediated transformation of cotton (Gossypium hirsutum L. cv.
      Zhongmian 35) using glyphosate as a selectable marker.
AB  - The most economically significant Chinese cotton cultivar (Gossypium hirsutum L.
      cv. Zhongmian 35) was transformed via Agrobacterium tumefaciens-mediated DNA
      transfer. The aroA-M1 gene that confers resistance to the glyphosate was fused
      with a chloroplast-transit peptide of Arabidopsis thaliana 5-enolpyruvyl-3
      phosphoshikimate synthase (ASP) and expressed in cotton plants under the control
      of a CaMV35S promoter. Transgenic plants were directly selected on medium
      containing glyphosate. Thirty-four independent transgenic lines were obtained
      after selection, giving a maximal 1.9% transformation frequency. The integration
      and expression of the aroA-M1 gene in T(0) plants and T(1) progeny were confirmed
      using DNA hybridization, Western blot and PCR techniques. An increased resistance
      of T(0) and T(1 )transgenic plants towards glyphosate was also observed.

PMID- 16799757
TI  - Enhancement of polyunsaturated fatty acid production by Tn5 transposon in
      Shewanella baltica.
AB  - Transposon Tn5 mutagenesis was used to generate random mutations in Shewanella
      baltica MAC1, a polyunsaturated fatty acid (PUFA)-producing bacterium. Three
      mutants produced 3-5 times more eicosapentaenoic acid (EPA 20:5 n-3) compared to
      the wild type at 10 degrees C. One of the mutants produced 0.3 mg EPA g(-1) when
      grown at high temperature (30 degrees C). Moreover, 2 mg docosahexaenoic acid
      (DHA 22:6 n-3) g(-1) was produced by S. baltica mutants at 4 degrees C.
      Sequencing of insertion mutation(s) showed 96% homology to trimethylamine N-oxide
      (TMAO) reductase gene and 85% homology to rRNA operons of E. coli. Tn5 transposon
      mutagenesis therefore is a suitable technique to increase PUFA formation in
      bacteria.

PMID- 16799758
TI  - A simple, rapid and effective method for total RNA extraction from Lentinula
      edodes.
AB  - A rapid, inexpensive and reliable method for total RNA extraction from fruiting
      bodies of Lentinula edodes containing large quantities of polysaccharides and
      secondary metabolites is described. An initial extraction step using saturated
      NaCl solution facilitates the separation of nucleic acids from contaminants and,
      after further extraction with organic solvents and precipitation with 2-propanol,
      total RNA of high purity and suitable for applications such as cDNA synthesis, RT
      PCR and Northern blot hybridization was obtained. The procedure may also have
      wider applicability for total RNA extraction from the tissues of other mushrooms.

PMID- 16799759
TI  - Improvement of expression level and bioactivity of soluble tumor necrosis factor
      related apoptosis-inducing ligand (Apo2L/TRAIL) by a novel zinc ion feeding
      strategy.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) is a
      new member of the TNF superfamily. In this work, the key role of Zn(2+) in high
      level expression of soluble TRAIL was confirmed. The yield of soluble TRAIL
      reached 1.6 g l(-1) using a novel, two-stage Zn(2+) feeding strategy, and the
      accumulation of TRAIL inclusion bodies decreased. Furthermore, the purified TRAIL
      showed stronger cytotoxicity activity against human pancreatic 1990 tumor cells
      as the molar ratio of Zn(2+) to TRAIL monomer was 2 in purified TRAIL solution.

PMID- 16799760
TI  - Functional expression of the astaxanthin biosynthesis genes from a marine
      bacterium, Paracoccus haeundaensis.
AB  - The astaxanthin biosynthesis gene cluster in Paracoccus haeundaensis consists of
      six genes: crtW, crtZ, crtY, crtI, crtB, and crtE contain 726, 486, 1158, 1503,
      912, and 879 base pairs, respectively. Individual carotenoid biosynthesis genes
      of P. haeundaensis have now been expressed in E. coli and each gene product has
      been purified to homogeneity. Their molecular characteristics, including
      enzymatic activities, are reported here.

PMID- 16799762
TI  - Immobilization of permeabilized whole cell penicillin G acylase from Alcaligenes
      faecalis using pore matrix crosslinked with glutaraldehyde.
AB  - The activity of penicillin G acylase from Alcaligenes faecalis increased 7.5-fold
      when cells were permeabilized with 0.3% (w/v) CTAB. The treated cells were
      entrapped by polyvinyl alcohol crosslinked with boric acid, and crosslinked with
      2% (v/v) glutaraldehyde to increase the stability. The conversion yield of
      penicillin G to 6-aminopenicillanic acid was 75% by immobilized system in batch
      reaction. No activity was lost after 15 cycles and about 65% enzyme activity was
      retained at the end of the 31th cycle.

PMID- 16799761
TI  - Enhanced ginsenoside productivity by combination of ethephon and methyl jasmoante
      in ginseng (Panax ginseng C.A. Meyer) adventitious root cultures.
AB  - Ethephon at 50 microM enhanced both root growth and ginsenoside accumulation in
      ginseng (Panax ginseng C.A. Meyer) adventitious root cultures, but at 100 microM
      it inhibited only ginsenoside accumulation. Ginsenoside productivity with 50
      microM ethephon was the highest at 1.7 mg l(-1) d(-1) after 8 days of
      elicitation. However, elicitation with 50 microM ethephon and 100 microM methyl
      jasmonate (MJ) improved productivity (6.3 mg l(-1) d(-1)) whereas elicitation
      with 100 microM MJ alone gave only 2.9 mg l(-1) d(-1).

PMID- 16799763
TI  - Detection of surface asialoglycoprotein receptor expression in hepatic and extra
      hepatic cells using a novel monoclonal antibody.
AB  - The asialoglycoprotein receptor (ASGPR) is a heterodimeric membrane protein which
      is involved in the internalization of desialylated glycoproteins and also in the
      binding and uptake of various pathogenic viruses. To facilitate the analysis of
      ASGPR expression, we generated a monoclonal antibody, termed ASSA-1, that is
      specific to the ASGPR H1 subunit based on ELISA and Western blots analysis. ASSA
      1 also reacted to surface-displayed ASGPR in live cells thus enabling analysis of
      ASGPR expression by immunofluorescence flow cytometry, which we used to analyze
      established human liver cell lines previously confirmed to be positive for ASGPR
      mRNA expression. In agreement with previous reports, surface ASGPR was also
      detected in extra-hepatic cells and, surprisingly, even in human T cell lines,
      which was then further confirmed in activated, but not in resting, primary human
      peripheral blood lymphocytes. These observations suggest that ASGPR has a broad
      pattern of expression that even extends into cells from the immune system, which
      biological meanings still have to be analyzed. We expect that monoclonal antibody
      ASSA-1 will serve as a new powerful tool in analyzing the biological role of
      ASGPR in hepatic and extra-hepatic cells.

PMID- 16799764
TI  - Over-expression and characterization of the recombinant small heat shock protein
      from Pyrococcus furiosus.
AB  - The gene encoding a small heat shock protein (sHSP) from Pyrococcus furiosus was
      redesigned and chemically synthesized by using bacteria-preferred codons. The
      gene product was over-expressed in Escherichia coli BL21(DE)(3) and purified to
      homogeneity. In the presence of this protein, the activities of Taq DNA
      polymerase, DNA restriction endonuclease HindIII and lysozyme were protected at
      elevated temperature, and also, thermal aggregation of lysozyme was prevented by
      this purified recombinant sHSP.

PMID- 16799765
TI  - Derivation of a growth hormone gene cassette for goat by mutagenesis of the
      corresponding bovine construct and its expression in Pichia pastoris.
AB  - Recombinant bovine growth hormone (rbGH), a 191-aa polypeptide that affects
      animal growth and lactation, has been used for several years to increase milk
      production in dairy cattle. It has also been used in goats (Capra hircus) instead
      of their own hormone (chGH), which is still not available in the market. Since
      both hormones differ in only one amino acid residue, a strategy based on PCR
      mediated site-directed mutagenesis, was used to convert the bGH expression
      cassette harbored by an integration plasmid for Pichia pastoris into a chGH.
      Transformation by homologous recombination of Pichia pastoris GS115 strain with
      the linearized new plasmid resulted in transformants that, upon fermentation and
      induction with methanol, secreted a band with the expected size and
      immunoreactivity for GH. Production of total proteins secreted into culture
      medium (50 ml) was 20 microg/ml, of which 60% was chGH as judged by densitometry
      in SDS-PAGE. Its biological activity was confirmed in vitro when 3T3 pre
      adipocytes exposed to the induced culture medium differentiated into adipocytes
      in cell culture.

PMID- 16799766
TI  - Functional evaluation of a novel constitutive promoter F1 of Bacillus pumilus, as
      a rice epiphytic strain, and construction of an efficient expression and
      secretion system under the control of F1.
AB  - To establish a constitutive, high-efficiency expression and secretion system for
      Bacillus pumilus, the function of a promoter and the abilities of three signal
      peptides in B. pumilus DX01 were tested. F1, cloned from the rice epiphyte B.
      pumilus strain DX01, had strong transcription activity and was a vegetative-phase
      constitutive promoter. The signal sequences of Bacillus subtilis levansucrase
      (sacB) and subtilisin, as well as B. pumilus DX01 RNase signal sequence could
      drive the secretion of E. coli beta-lactamase from B. pumilus DX01 efficiently,
      among which the signal sequence of B. subtilis sacB was the most effective.
      Likewise, they could also direct the secretion of green fluorescence protein
      (GFP) from DX01.

PMID- 16799767
TI  - Construction of a bacterial artificial chromosome library and characterization of
      hrp/hrc gene cluster of Pseudomonas syringae pathovar tagetis LMG5090.
AB  - Pseudomonas syringae pv. tagetis causes apical chlorosis of several plant species
      in the Asteraceae, including marigold. As a means to facilitate the isolation of
      pathogenicity genes and to characterize the genome of this bacterium, we have
      constructed a bacterial artificial chromosome library of P. syringae pv. tagetis
      strain LMG5090. The library consists of 1,536 clones with insert size ranging
      from 30 to 160 kb and an average size of 86 kb. Based upon colony hybridization,
      the BAC clone 420E23 containing the hrp/hrc gene cluster encoding the type III
      secretion system was identified from this library and subsequently shotgun
      sequenced. The hrp/hrc gene cluster of P. syringae pv. tagetis has a 23 kb
      sequence which contains 27 open reading frames. Comparative analysis of the
      hrp/hrc gene cluster of P. syringae pv. tagetis LMG5090, P. syringae pv. tomato
      DC3000, P. syringae pv. syringae B728a, and P. syringae pv. phaseolicola 1448A
      revealed that the entire hrp/hrc gene cluster of P. syringae pv. tagetis is
      conserved and identically arranged in all four pathovars.

PMID- 16799768
TI  - Ribosome-inactivating proteins: progress and problems.
AB  - Ribosome-inactivating proteins (RIPs), mostly from plants, are enzymes which
      depurinate rRNA, thus inhibiting protein synthesis. They also depurinate other
      polynucleotide substrates. The biological activity of RIPs is not completely
      clarified, and sometimes independent of the inhibition of protein synthesis.
      There are differences in the cytotoxicity of RIPs and, consequently, in their
      toxicity to animals. Some RIPs are potent toxins, the best known being ricin, a
      potential biological weapon. New toxins have recently been identified. RIPs cause
      apoptotic and necrotic lesions, and induce production of cytokines causing
      inflammation. RIPs are potentially useful in agriculture and medicine because (i)
      they have antiviral activity and (ii) they are used for the preparation of
      conjugates with antibodies ('immunotoxins') or other carriers, rendering them
      specifically toxic to the cell target of the carrier, which may be helpful in
      therapy. The distribution, mechanism of action and role in nature of RIPs are not
      completely understood, and we can expect several future developments in their
      practical application.

PMID- 16799769
TI  - Phytanic acid: production from phytol, its breakdown and role in human disease.
AB  - Phytanic acid is a branched-chain fatty acid that accumulates in a variety of
      metabolic disorders. High levels of phytanic acid found in patients can exceed
      the millimolar range and lead to severe symptoms. Degradation of phytanic acid
      takes place by alpha-oxidation inside the peroxisome. A deficiency of its
      breakdown, leading to elevated levels, can result from either a general
      peroxisomal dysfunction or from a defect in one of the enzymes involved in alpha
      oxidation. Research on Refsum disease, belonging to the latter group of disorders
      and characterized by a deficiency of the first enzyme of alpha-oxidation, has
      extended our knowledge of phytanic acid metabolism and pathology of the disease
      greatly over the past few decades. This review will centre on this research on
      phytanic acid: its origin, the mechanism by which its alpha-oxidation takes
      place, its role in human disease and the way it is produced from phytol.

PMID- 16799770
TI  - Virologists, taxonomy and the demands of logic.

PMID- 16799771
TI  - A sequential injection electronic tongue employing the transient response from
      potentiometric sensors for anion multidetermination.
AB  - Intelligent and automatic systems based on arrays of non-specific-response
      chemical sensors were recently developed in our laboratory. For
      multidetermination applications, the normal choice is an array of potentiometric
      sensors to generate the signal, and an artificial neural network (ANN) correctly
      trained to obtain the calibration model. As a great amount of information is
      required for the proper modelling, we proposed its automated generation by using
      the sequential injection analysis (SIA) technique. First signals used were steady
      state: the equilibrium signal after a step-change in concentration. We have now
      adapted our procedures to record the transient response corresponding to a sample
      step. The novelty in this approach is therefore the use of the dynamic components
      of the signal in order to better discriminate or differentiate a sample. In the
      developed electronic tongue systems, detection is carried out by using a sensor
      array formed by five potentiometric sensors based on PVC membranes. For the
      developed application we employed two different chloride-selective sensors, two
      nitrate-selective sensors and one generic response sensor. As the amount of raw
      data (fivefold recordings corresponding to the five sensors) is excessive for an
      ANN, some feature extraction step prior to the modelling was needed. In order to
      attain substantial data reduction and noise filtering, the data obtained were
      fitted with orthonormal Legendre polynomials. In this case, a third-degree
      Legendre polynomial was shown to be sufficient to fit the data. The coefficients
      of these polynomials were the input information fed into the ANN used to model
      the concentrations of the determined species (Cl-, NO3- and HCO3-). Best results
      were obtained by using a backpropagation neural network trained with the Bayesian
      regularisation algorithm; the net had a single hidden layer containing three
      neurons with the tansig transfer function. The results obtained from the time
      dependent response were compared with those obtained from steady-state
      conditions, showing the former superior performance. Finally, the method was
      applied for determining anions in synthetic samples and real water samples, where
      a satisfactory comparison was also achieved.

PMID- 16799772
TI  - Electrical impedance tomography: Ready for prime time?

PMID- 16799773
TI  - Body and head position effects on regional lung ventilation in infants: An
      electrical impedance tomography study.
AB  - OBJECTIVE: To determine the effects of body and head positions on the spatial
      distribution of ventilation in nonintubated spontaneously breathing and
      mechanically ventilated infants using electrical impedance tomography (EIT).
      DESIGN AND SETTING: Prospective study in a neonatal intensive care unit.
      PATIENTS: Ten spontaneously breathing (gestational age 38 weeks, postnatal age 13
      days) and ten mechanically ventilated infants (gestational age 35 weeks,
      postnatal age 58 days). INTERVENTIONS: Supine and prone postures with different
      head positions (midline and rotated to the left and right side). MEASUREMENTS AND
      RESULTS: The distribution of ventilation in the chest cross-section was
      repeatedly determined from EIT data in each body/head position studied. During
      spontaneous breathing the tidal volumes in the left lung region were reduced in
      the supine posture with the head turned to the left as well as in the prone
      posture with the head rotated to either side when compared with the supine
      posture with the head in the midline position. During mechanical ventilation the
      tidal volumes in the left lung region were unaffected by the body and head
      position except for the prone posture combined with the leftward head rotation
      which reduced them. In both types of ventilation the tidal volumes in the right
      lung region were unaffected by the change in body/head position. CONCLUSION: The
      results indicate that the spatial distribution of ventilation is influenced by
      the body and head position in spontaneously breathing infants. Prone posture with
      the leftward head rotation has the most prominent effect which is detectable even
      during mechanical ventilation.

PMID- 16799774
TI  - C-reactive protein concentrations during bacteraemia: A comparison between
      patients with and without liver dysfunction.
AB  - OBJECTIVE: To evaluate the value of serum C-reactive protein (CRP) concentrations
      as a marker of sepsis in patients with biochemical evidence of liver dysfunction.
      DESIGN: A retrospective case-control comparison of serum CRP concentrations
      between patients with and those without liver dysfunction (prothrombin time over
      18 s and serum bilirubin > or = 20 micromol/l) during their first episode of
      bacteraemia. SETTING: The neurosciences and general adult intensive care units of
      a university teaching hospital. PATIENTS: Any patient from the above settings
      with a first episode of bacteraemia (first isolate of pathogenic bacteria from
      blood cultures) over a 3-year period. MEASUREMENTS AND RESULTS: After exclusions
      126 first episodes of bacteraemia were identified, of which 33 were in patients
      with liver dysfunction. Serum CRP concentrations were significantly lower in
      patients with liver dysfunction (median 103 mg/l, IQR 29-204) than in those
      without (146 mg/l, 74, > 250). CONCLUSIONS: Patients with biochemical evidence of
      liver disease generate significantly lower serum CRP concentrations during
      bacteraemia than patients without liver dysfunction. Serum CRP concentrations
      should be interpreted with caution in patients with liver disease to diagnose and
      monitor bacterial sepsis.

PMID- 16799775
TI  - Increased use of noninvasive ventilation in French intensive care units.
AB  - OBJECTIVES: A prospective survey of French intensive care units (ICUs) in 1997
      showed moderate and variable use of noninvasive ventilation (NIV). This study
      examined changes in NIV use in French ICUs after the intervening 5years.
      SETTINGS: Patients were enrolled in a prospective survey in 70 French ICUs.
      METHODS: Three-week survey, with prospective inclusion of all patients requiring
      ventilatory support. MEASUREMENTS AND RESULTS: Overall 1,076 patients received
      ventilatory support (55% of admissions). First-line NIV was significantly more
      common than 5years earlier, overall (23% vs. 16%) and especially in patients not
      intubated before ICU admission (52% vs. 35%). Reasons for respiratory failure
      were coma (33%), cardiogenic pulmonary edema (8%), acute-on-chronic respiratory
      failure (17%), and de novo respiratory failure (41%). Significant increases in
      NIV use were noted for acute-on-chronic respiratory failure (64% vs. 50%) and de
      novo respiratory failure (22% vs. 14%). Among patients given NIV, 38%
      subsequently required endotracheal intubation (not significantly different).
      Independent risk factors for NIV failure were high SAPS II and de novo
      respiratory failure, whereas factors associated with success were good NIV
      tolerance and high body mass index. CONCLUSIONS: NIV use has significantly
      increased in French ICUs during the past 5years, and the success rate has
      remained unchanged. In patients not previously intubated, NIV is the leading
      first-line ventilation modality. The proportion of patients successfully treated
      with NIV increased significantly over the 5-year period (13% vs. 9% of all
      patients receiving ventilatory support).

PMID- 16799776
TI  - The reliability and validity of the Turkish version of the Western Ontario
      Rotator Cuff Index.
AB  - To adapt the Western Ontario Rotator Cuff (WORC) index for use in Turkey and to
      investigate its reliability and validity; the Turkish version of the WORC was
      developed according to the guidelines in the literature. Seventy-two patients
      with rotator cuff disease were administered the questionnaire and were also
      evaluated by using the University of California Los Angeles (UCLA) shoulder
      rating scale, Constant score, and Short Form (SF)-36 to test validity. The WORC
      questionnaire was repeated in 35 patients after a mean interval of 2.9 days
      (range 2-7 days) to evaluate test-retest reliability. Cronbach's alpha was
      calculated as 0.92 for the total questionnaire. The intraclass correlation
      coefficients were very high and ranged between 0.96 and 0.98 for each section.
      There was a significant negative correlation between the Turkish version of WORC
      and UCLA (r = -0.598, P < 0.01), Constant score (r = -0.630, P < 0.01), and all
      subscales of SF-36 (P < 0.01). The Turkish version of the WORC index is a
      reliable and valid instrument for use in clinical trials in patients with rotator
      cuff disorders.

PMID- 16799777
TI  - The treatment of the rheumatological manifestations of the inflammatory bowel
      diseases.
AB  - The strong link between the bowel and the osteo-articular system is suggested by
      many clinical and experimental observations. However, the therapeutic approach is
      still empirical. For symptomatic therapy it is better to favour the use of
      steroids and avoid non-steroidal anti-inflammatory drugs because they may induce
      intestinal ulcerations and can activate inflammatory bowel disease. Second line
      drugs (sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide)
      should be used for selected indications. In some cases (severe spondylitis,
      severe and persistent enthesopathy) anti-TNF-alpha agents (infliximab) should be
      considered as first line therapy. In all cases it is mandatory to select the best
      therapeutic option for each individual patient, considering that the optimal
      treatment of bowel inflammation may induce "per se" a remission of the musculo
      skeletal manifestations.

PMID- 16799779
TI  - The role of the determination of the CD20 antigen through quantitative flow
      cytometry in complex cases of rheumatoid arthritis treated with anti-TNF-alpha.

PMID- 16799778
TI  - Anti-tumour necrosis factor-alpha therapy over conventional therapy improves
      endothelial function in adults with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is associated with cardiovascular morbidity and
      mortality and inflammation contributes to related endothelial dysfunction. We
      aimed to investigate the effect of anti-TNFalpha therapy on endothelial function
      in subjects with rheumatoid arthritis. We measured flow-mediated (FMD) and GTN
      mediated dilation of the brachial artery before and following 36 weeks of anti
      TNFalpha therapy in nine RA patients and in a group of RA patients on
      conventional therapy. Thirty-six weeks of anti-TNFalpha therapy improved FMD
      relative to those on conventional therapy (8.65 +/- 1.50 vs. 1.70 +/- 1.36%, P =
      0.02). No significant changes in GTN responses were evident. Significant
      improvements in tender (P = 0.03) and swollen (P = 0.02) joint counts, patients'
      global self-assessment (P = 0.01) and DAS-28 scores (P = 0.04) were observed in
      the anti-TNFalpha treated group. The addition of anti-TNFalpha treatment to
      conventional therapy, in those with severe RA, reduces inflammatory symptoms and
      improves endothelial function, potentially lowering future atherosclerotic risk.

PMID- 16799780
TI  - Rosiglitazone modifies the adipogenic potential of human muscle satellite cells.
AB  - AIMS/HYPOTHESIS: Satellite cells are responsible for postnatal skeletal muscle
      regeneration. It has been demonstrated that mouse satellite cells behave as
      multipotent stem cells. We studied the differentiation capacities of human
      satellite cells and evaluated the effect of the insulin sensitiser rosiglitazone,
      a well known peroxisome proliferative activated receptor gamma (PPARG) agonist,
      on their adipogenic conversion. SUBJECTS, MATERIALS AND METHODS: We obtained
      human satellite cells from human muscle biopsies of healthy subjects by single
      fibre isolation and cultured them under myogenic, osteogenic and adipogenic
      conditions. Moreover, we compared the morphological features and the adipose
      specific gene expression profiling, as assessed by quantitative PCR, between
      adipocytes differentiated from human satellite cells and those obtained from the
      stromal vascular fraction of human visceral fat. RESULTS: We proved by
      morphological analysis, mRNA expression and immunohistochemistry that human
      satellite cells are able to differentiate into myotubes, adipocytes and
      osteocytes. The addition of rosiglitazone to the adipogenic medium strongly
      activated PPARG expression and enhanced adipogenesis in human satellite cells,
      but did not in itself trigger the complete adipogenic programme. Moreover, we
      observed a decrease in wingless-type MMTV integration site family member 10B and
      an upregulation of growth differentiation factor 8 expression, both being
      independent of PPARG activation. CONCLUSIONS/INTERPRETATION: Human satellite
      cells possess a clear adipogenic potential that could explain the presence of
      mature adipocytes within skeletal muscle in pathological conditions such as
      obesity, type 2 diabetes and ageing-related sarcopenia. Rosiglitazone treatment,
      while enhancing adipogenesis, induces a more favourable pattern of adipocytokine
      expression in satellite-derived fat cells. This could partially counteract the
      worsening effect of intermuscular adipose tissue depots on muscle insulin
      sensitivity.

PMID- 16799782
TI  - Assessment of Crohn's disease in the small bowel: Prospective comparison of
      magnetic resonance enteroclysis with conventional enteroclysis.
AB  - Our objective was to assess the diagnostic value of magnetic resonance
      enteroclysis (MRE) compared with conventional enteroclysis (CE) in patients with
      Crohn's disease. A secondary objective was to evaluate the diagnostic accuracy of
      each different MR sequence. Sixty-six consecutive patients with known Crohn's
      disease underwent MRE and CE. Fast imaging employing steady-state acquisition
      (FIESTA), single-shot fast spin-echo (ssFSE), and contrast-enhanced T1-weighted
      sequences were assessed by two radiologists who reached a consensus about the
      following findings: visualization of wall ulcers, pseudopolyps, fistulae, mural
      stenosis, and mesenteric abnormalities. Standard descriptive statistics and the
      McNemar test were used. The sensitivity, specificity and accuracy of MRE were 90
      87% and 83% for the depiction of parietal ulcers, 84%-88% and 86% for
      pseudopolyps, 100-94% and 96% for mural stenosis, 93-100% and 94% for fistulae.
      The number of detected extraluminal findings was significantly higher with MRE (P
      < 0.01). The accuracy of FIESTA sequence was statistically higher in the
      depiction of wall ulcers and fistulae than that of three-dimensional fast spoiled
      gradient echo (3D-FSPGR) (P < 0.01) and ssFSE (P < 0.05) sequences. Contrast
      enhanced 3D-FSPGR was superior for mural stenosis visualization compared to ssFSE
      (P < 0.05) and FIESTA (P < 0.05). MRE correlates accurately with CE in the
      detection of superficial and transmural abnormalities and has the advantage of
      assessing the mesenteric manifestations.

PMID- 16799781
TI  - Interobservational variation in determining fusion rates in anterior cervical
      discectomy and fusion procedures.
AB  - The fusion rate represents one of the most commonly used criteria for evaluating
      the efficacy of spinal surgical techniques and the effectiveness of newly
      developed instrumentation and spinal implants. Reported fusion rates are not
      frequently supported by adequate information regarding by whom and how fusion was
      defined. In our prospective study we examined the fusion rate in patients
      undergoing first time anterior cervical discectomy and fusion for degenerative
      disease. Separate, well-defined radiographic fusion criteria were used and the 12
      month post-operative X-rays were reviewed independently by a neurosurgeon, a
      neuroradiologist and an orthopedic surgeon, who were not involved in the
      patients' management. The observed fusion rates were 77.3, 87.8 and 84.7%
      respectively. Statistical analysis demonstrated concordance rates of 87.8, 91 and
      91.4% and Kappa coefficients of 0.585, 0.620 and 0.723 for each pair of
      evaluators. Another set of ratings of the same radiographs, by the same
      interviewers, was obtained 6 weeks after the initial one. The reported fusion
      rates were 78.2% for the neurosurgeon, 87.4% for the orthopedic surgeon, and
      86.1% for the neuroradiologist. Statistical analysis demonstrated intra-observer
      concordance rates of 98.7, 92.2 and 97.9% respectively, while the Kappa
      coefficients were 0.963, 0.677 and 0.907 for each reviewer. Our findings confirm
      the necessity of defining and describing criteria for fusion whenever this rate
      is reported in clinical series. The lack of widely accepted, well-defined
      criteria makes comparison of these results difficult. The development of a well
      organized, prospective clinical study in which fusion and outcome will be
      assessed by both clinical and radiographic parameters could significantly
      contribute to a more accurate evaluation of overall outcome of cervical spinal
      procedures.

PMID- 16799783
TI  - Preoperative assessment and follow-up of congenital abnormalities of the
      pulmonary arteries using CT and MRI.
AB  - Congenital heart disease (CHD), including complex anomalies of the pulmonary
      arteries, are now earlier diagnosed and treated. Due to improvements in
      interventional and surgical therapy, the number of patients with the need for
      follow-up examinations is increasing. Pre- and postinterventional imaging should
      be done as gently as possible, avoiding invasive techniques if possible. With the
      technical improvement of multidetector-row computed tomography (MDCT) and
      magnetic resonance imaging (MRI), both techniques are increasingly used for
      noninvasive assessment of the pulmonary vasculature in children with CHD.
      Knowledge of the most common diseases affecting the pulmonary vasculature and the
      kind of surgical and interventional procedures is essential for optimal imaging
      planning. This is especially important because interventions can be positively
      influenced by high-quality imaging. Therefore, the most common diseases and
      procedures are described and imaging modality of choice and important image
      findings are discussed.

PMID- 16799784
TI  - Coexisting secondary intraneural and vascular adventitial ganglion cysts of joint
      origin: a causal rather than a coincidental relationship supporting an articular
      theory.
AB  - OBJECTIVE: To introduce the clinical entity of an intraneural ganglion cyst
      coexisting with a vascular adventitial cyst arising from the same joint. DESIGN:
      Retrospective review. PATIENTS: Two patients presented with predominantly deep
      peroneal neuropathy due to complex superior tibiofibular joint-related cysts. In
      addition to having peroneal intraneural ganglion cysts, these patients had
      vascular adventitial cysts: one involving a capsular arterial branch, the other a
      capsular vein [as well as a large, recurrent, intramuscular (extraneural)
      ganglion]. We then reviewed MRIs of 12 other consecutive cases of intraneural
      ganglia (10 peroneal and 2 tibial) arising from the superior tibiofibular joint
      that we treated, as well as other reported cases in the literature to determine
      if there were other (unrecognized) examples supporting the combination of
      clinical findings and radiographic patterns. RESULTS: Retrospective analysis of
      MRIs in the two surgically proven cases of peroneal intraneural ganglia with
      vascular adventitial cyst extension showed a common imaging pattern that we have
      termed "the wishbone sign," consisting of the connection of the ascending limb of
      the peroneal intraneural ganglion and the longitudinal limb of the vascular
      adventitial cyst in the axial plane. Our review suggests that vascular
      adventitial cyst extension occurs in a large proportion of cases of peroneal
      intraneural ganglia. A similar growth pattern was noted in a case of a tibial
      intraneural ganglion. CONCLUSIONS: The combination of intraneural and vascular
      adventitial cysts is understandable given our knowledge of normal and pathologic
      anatomy of para-articular cysts. The combination of intraneural ganglia and
      vascular adventitial cysts broadens the spectrum of clinical presentations of
      these cysts and suggests that cysts and their content can dissect from a joint
      along neurovascular bundles. These cases provide important evidence to support
      the articular theory for the pathogenesis of not only neural but vascular
      adventitial cysts as well.

PMID- 16799785
TI  - Radiography of successful bone marrow transplantation for osteopetrosis.
AB  - Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for
      autosomal recessive infantile malignant osteopetrosis, an otherwise fatal
      disease. HSCT has also been utilized in patients with the less severe autosomal
      recessive intermediate form in an attempt to correct hematologic abnormalities
      and halt cranial nerve deficits caused by progressive cranial foraminal stenosis.
      Successful engraftment is accompanied by rapid normalization of radiographic
      signs of osteopetrosis.

PMID- 16799786
TI  - The relative biological effectiveness of densely ionizing heavy-ion radiation for
      inducing ocular cataracts in wild type versus mice heterozygous for the ATM gene.
AB  - The accelerated appearance of ocular cataracts at younger ages has been recorded
      in both astronauts and airline pilots, and is usually attributed to high-energy
      heavy ions in galactic cosmic ray radiation. We have previously shown that high
      LET 1-GeV/nucleon (56)Fe ions are significantly more effective than X-rays in
      producing cataracts in mice. We have also shown that mice haploinsufficient for
      ATM develop cataracts earlier than wild-type animals, when exposed to either low
      LET X-rays or high-LET (56)Fe ions. In this paper we derive quantitative
      estimates for the relative biological effectiveness (RBE) of high energy (56)Fe
      ions compared with X-rays, both for wild type and for mice haploinsufficient for
      ATM. There is a clear trend toward higher RBE's in haploinsufficient animals,
      both for low- and high-grade cataracts. Haploinsufficiency for ATM results in an
      enhanced sensitivity to X-rays compared with the wild type, and this enhancement
      appears even larger after exposure to high-LET heavy ions.

PMID- 16799787
TI  - Prenatal diagnosis of choledochal cyst by magnetic resonance cholangiography.

PMID- 16799788
TI  - Liver, meconium, haemorrhage: the value of T1-weighted images in fetal MRI.
AB  - BACKGROUND: Ultrafast T2-weighted (T2-W) MRI sequences are currently considered a
      routine technique for fetal MR imaging. Limited experience exists with fetal T1
      weighted (T1-W) imaging techniques. OBJECTIVE: To determine MRI patterns of some
      fetal abdominal or haemorrhagic disorders with particular respect to the
      diagnostic value of T1-W images. MATERIALS AND METHODS: In addition to standard
      T2-W single-shot sequences, T1-W single-shot and/or multislice sequences were
      employed in 25 MR examinations performed in 23 fetuses between 20 and 36 weeks of
      gestation for more detailed assessment of liver, meconium-filled digestive tract,
      haemorrhage, or further characterization of a fetal abdominal mass. Diagnostic
      value and presence of motion artefacts on T1-W images was recorded in each case.
      RESULTS: T1-W images enabled superior delineation of fetal liver and large
      intestine. They provided additional diagnostic information in 9 (39%) of 23
      fetuses. One false-positive and one false-negative MRI diagnosis of malrotation
      anomaly were encountered. Use of single-shot T1-W sequences reduced the
      occurrence of motion artefacts in 64%. CONCLUSION: Our results suggest that the
      specific signal properties of methaemoglobin, meconium and liver are sufficiently
      important for T1-W sequences to become a routine part of fetal MRI protocols when
      dealing with digestive tract anomalies, diaphragmatic and abdominal wall defects,
      intraabdominal masses, and fetal haemorrhage.

PMID- 16799789
TI  - Multiplanar angled reconstructions of reconstructions--a dangerous practice using
      multidetector CT.
AB  - This case illustrates the dangers of using reconstructions to correct for
      positioning in multiplanar CT scans and using images that have already been
      reconstructed rather than the original source images. We present a case where a
      subdural haemorrhage was simulated by reconstructing already reconstructed
      images.

PMID- 16799790
TI  - [Long-term oncological results after laparoscopic, converted and primary open
      procedures for rectal carcinoma. Results of a multicenter observational study].
AB  - BACKGROUND: The laparoscopic resection of rectal cancer shows morbidity and
      oncological safety comparable to the open approach, but morbidity increases after
      conversion to open resection. No oncological long-term results are available for
      the latter patients. METHODS: From 01/01/2000-31/12/2002, patients with
      curatively resected rectal cancer enrolled in a observational study were
      evaluated for morbidity, mortality, tumor- and local recurrence rate, paying
      attention to patients with conversion from laparoscopic to open resection.
      RESULTS: 237 (3.3%) of 7,189 patients underwent laparoscopic resection (ITT).
      These patients showed significantly more T1/2 tumors (P<0.001) in earlier UICC
      stages (P<0.001) than open resected patients. 35 (14.8%) of 237 laparoscopic
      procedures were converted. Compared with patients receiving complete laparoscopic
      or open resection, these patients showed significantly higher frequencies of
      intraoperative (P<0.001) and general postoperative complications (P=0.003) as
      well as the highest overall morbidity (P=0.031). After a median follow-up of 30.1
      months, the highest 5-year local recurrence rate was found in the converted group
      (16.0%). The laparoscopically resected patients showed a local recurrence rate of
      3.3%, patients with open resection of 12.4% (P=0.082). The disease-free survival
      rate did not differ between the groups (P=0.585). CONCLUSION: Laparoscopic
      resection of rectal cancer provides oncological results similar to open
      resection. After conversion, the short and oncological long-term outcomes were
      worse. Considering a conversion rate of 15%, only a strict indication for the
      laparoscopic approach can be allowed, and laparoscopic resection should be
      performed at centers.

PMID- 16799791
TI  - Prognostic factors of squamous cell carcinoma of the anal margin treated by
      radiotherapy: the Lyon experience.
AB  - BACKGROUND: To report our patient experience with squamous cell carcinoma of the
      anal margin and to evaluate the prognostic factors influencing outcome. MATERIALS
      AND METHODS: Between 1980 and 2001, 26 patients with anal margin squamous cell
      carcinoma were treated in Lyon-Sud: 7 T1, 14 T2, 4 T3, and 1 T4 with 20 N0, 3 N1,
      and 3 N2. The anal canal was invaded in five patients. Treatment consisted of
      definitive external irradiation in 14 patients and adjuvant irradiation (after a
      local excision) in 12 patients. External irradiation was combined with
      chemotherapy in seven patients, brachytherapy in four patients, and both
      brachytherapy and chemotherapy in one patient. RESULTS: The local control rate
      was initially 61.4%, and it was 80.8% after salvage treatment. The 5-year overall
      and specific survival rates were 71 and 88.3%, respectively. Three factors
      correlated with specific survival: cell differentiation (P=0.038) and T (P=0.001)
      and N category (P=0.0005). A salvage abdominoperineal resection was successfully
      employed in five of seven local recurrences. Four grade 3 and two grade 4
      toxicities were observed. Sphincter preservation was possible in 66% of alive
      patients. CONCLUSION: Our results confirm the dominating place of definitive
      irradiation and radiochemotherapy in the treatment of anal margin squamous cell
      carcinoma. The indications for abdominoperineal resection must be limited to
      local relapse. The prognosis of squamous cell carcinoma is correlated to T and N
      staging and cell differentiation.

PMID- 16799792
TI  - Long-term results of HA coated threaded versus HA coated hemispheric press fit
      cups: 287 hips followed for 11 to 16 years.
AB  - INTRODUCTION: There are many studies on the short and medium term results of
      hydroxyapatite (HA) coated acetabular components, but information on survival in
      the longer run is sparse. In this paper, we report 11 to 16 years follow up
      results of HA coated threaded versus HA coated hemispherical press fit cups.
      PATIENTS AND METHODS: During the years 1988-1993, we performed 323 primary total
      hip replacements in 276 patients with an HA coated acetabular component. In 128
      cases we used a HA coated threaded cup, and in 195 cases a HA coated
      hemispherical press fit cup was inserted. There were 189 women and 87 men aged 15
      79 (mean 48) years. During follow-up, 14 patients died and 21 patients would not
      come for the follow-up examination as they were doing quite well with their
      prostheses. These patients were censored at their last control examination. This
      left 241 patients (287 hips) followed for 11 to 16 (mean 13) years after the
      operation. RESULTS: During the follow-up period 48 press fit cups and 9 threaded
      cups were revised, none because of infection. Survival analyses indicated a
      cumulative survival of the threaded HA coated cup of 0.91 (95% CI: 0.86-0.97) at
      16 years with one patient at risk. The cumulative survival of the HA coated press
      fit cup was 0.74 (0.69-0.80) at 15 years with no patient at risk. The difference
      is significant (P = 0.0002). Wear and age was significantly associated with
      revision (P < 0.0001 and 0.0002, respectively), and wear was significantly (P <
      0.0001) associated with osteolysis. CONCLUSION: These results indicate that HA
      coated threaded cups provide satisfactory bony interlock to resist force loads in
      the long run whereas the HA coated hemispherical press fit cups do not.

PMID- 16799793
TI  - Does total knee joint replacement with the soft tissue balancing surgical
      technique maintain the natural joint line?
AB  - INTRODUCTION: The outcomes of 106 total knee arthroplasties implanted using a
      soft tissue balancing surgical technique at one surgical centre were used to
      assess the accuracy maintaining the knee's original joint line (JL). The aim of
      the study was to determine whether there is a shift of the presumed joint line
      after surgery. MATERIALS AND METHODS: Preoperative and post-operative radiographs
      were compared to determine any changes in the articulation height. The
      preoperative distance of the fibular head to the natural joint line was measured
      and compared with the post-operative measurement of the fibular head to the
      femoral articulation line (measured on the radiograph and defined as Rxmm). Based
      on the actual medio-lateral dimension of the tibial metal back, the measured
      difference (RXmm) could be converted into true distances (in mm). The Blackburn
      Peel index was assessed as an additional outcome prior to and following surgery.
      RESULTS: Preoperatively, the average distance from the fibular head to the joint
      line was 15.1 Rxmm (SD 4.3) while the post-surgical distance was 15.5 Rxmm (SD
      5.6). The average deviation of the post-surgical JL in relation to the original
      JL amounted to 0.4 Rxmm (SD 3.7). The average deviation of the joint line
      converted into the true distance was -0.3 mm (with a range of -5.9 mm in distal
      direction to + 8.3 mm in the proximal direction). Valgus position appeared to
      generate rather a shift in proximal direction whereas varus deformity favours a
      shift in distal direction. Seven patients exhibited a deviation of more than 5 mm
      in either the distal or proximal direction. All of the patients of this subgroup
      had a preoperative anatomical abnormality including a severe malalignment,
      serious bone destruction or had previously undergone a high tibial osteotomy.
      CONCLUSION: An exact reconstruction of the natural Joint Line is achievable when
      using the described soft tissue balancing surgical technique with the posterior
      cruciate ligament (PCL) retaining prosthesis design used in this series.

PMID- 16799794
TI  - [100 years sexual medicine].

PMID- 16799795
TI  - Iridodial: a powerful attractant for the green lacewing, Chrysopa septempunctata
      (Neuroptera: Chrysopidae).
AB  - The lacewing Chrysopa septempunctata Wesmael is an important, common predator of
      several insects in China, Japan, Russia, and many parts of Europe. Our field
      trapping experiments in northeast China showed that males of this green lacewing
      are strongly attracted to the lacewing pheromone of Chrysopa oculata Say,
      (1R,2S,5R,8R)-iridodial. The induced plant volatile, methyl salicylate, was
      unattractive to C. septempunctata by itself at the concentration tested, but
      synergistic when combined with iridodial where the lacewing population was high.
      (1R,4aS,7S,7aR)-Nepetalactol and (4aS,7S,7aR)-nepetalactone (aphid sex pheromone
      components) caught significantly more males of C. septempunctata than did blank
      control traps, but were inferior to iridodial dispensers, which remained strongly
      attractive to C. septempunctata males for at least 2.5 months. These results
      indicate that (1R,2S,5R,8R)-iridodial is a powerful attractant for C.
      septempunctata, and may have great potential for enhanced biological control of
      garden, agricultural, and forest insect pests.

PMID- 16799796
TI  - Induced resistance enzymes in wild plants-do 'early birds' escape from pathogen
      attack?
AB  - Systemic acquired resistance (SAR) of plants to pathogens is a well-defined
      phenomenon. The underlying signalling pathways and its application in crop
      protection are intensively studied. However, most studies are conducted on crop
      plants or on Arabidopsis as a model plant. The taxonomic distribution of this
      phenomenon and its dependence on life history are thus largely unknown. We
      quantified activities of three classes of resistance-related enzymes in 18 plant
      species to investigate whether plants with varying life histories differ in their
      investment in disease resistance. Enzyme activities were quantified in untreated
      plants, and in plants induced with BION, a chemical resistance elicitor. All
      species showed constitutive activities of chitinase, peroxidase, or glucanase.
      However, constitutive chitinase activities varied by 30 times, and peroxidase by
      50 times, among species. Several species did not respond to the induction
      treatment, while enzyme activities in other species increased more than threefold
      after BION application. Plant species differ dramatically in the presence and
      inducibility of resistance enzymes. This variation could be related to life
      history: While all resistance enzymes were significantly induced in larger
      perennial plants that flower during summer, spring geophytes hardly showed
      inducible resistance. These plants grow in an environment that is characterised
      by a low-pathogen pressure, and thus may simply 'escape' from infection. Our
      study presents the first comparative data set on resistance-related enzymes in
      noncultivated plants. The current view on SAR-narrowed by the concentration on
      cultivated crops-is not sufficient to understand the ecological and evolutionary
      relevance of this widespread plant trait.

PMID- 16799797
TI  - A link between eumelanism and calcium physiology in the barn owl.
AB  - In many animals, melanin-based coloration is strongly heritable and is largely
      insensitive to the environment and body condition. According to the handicap
      principle, such a trait may not reveal individual quality because the production
      of different melanin-based colorations often entails similar costs. However, a
      recent study showed that the production of eumelanin pigments requires relatively
      large amounts of calcium, potentially implying that melanin-based coloration is
      associated with physiological processes requiring calcium. If this is the case,
      eumelanism may be traded-off against other metabolic processes that require the
      same elements. We used a correlative approach to examine, for the first time,
      this proposition in the barn owl, a species in which individuals vary in the
      amount, size, and blackness of eumelanic spots. For this purpose, we measured
      calcium concentration in the left humerus of 85 dead owls. Results showed that
      the humeri of heavily spotted individuals had a higher concentration of calcium.
      This suggests either that plumage spottiness signals the ability to absorb
      calcium from the diet for both eumelanin production and storage in bones, or that
      lightly spotted individuals use more calcium for metabolic processes at the
      expense of calcium storage in bones. Our study supports the idea that eumelanin
      based coloration is associated with a number of physiological processes requiring
      calcium.

PMID- 16799798
TI  - Characteristics of HIV-infected children recently diagnosed in Paris, France.
AB  - Pediatric HIV-1 infections are still being diagnosed in France, despite the
      efficacy of prophylactic treatment to prevent mother-to-child transmission. To
      describe the characteristics and mode of infection of these children, we
      retrospectively analysed data of 59 children diagnosed with the HIV-1 infection
      between January 2000 and June 2005 in a Parisian university hospital. Twenty of
      these children had been born in France, and none had received appropriate
      prophylaxis (insufficient, not taken or given too late). Six received no
      preventive treatment due to failures in screening: three mothers were HIV
      seronegative at the start of pregnancy and no test was carried out for the other
      three. At diagnosis, four had a severe immune deficiency (CD4 cells <15%). The 39
      children born abroad were diagnosed at a median age of 3 years (range: 3 months
      16 years), sometimes several years after their arrival in France. The clinical,
      virological and immunological status of these children was poorer than that of
      the children born in France: 18 had less than 15% CD4 cells. In contrast, the
      response to treatment of the children born in France was not as good as that of
      the children born abroad. The HIV-1 screening and prevention programme for
      pregnant women could be improved. Some children infected following the failure of
      prevention are at high risk of subsequent treatment failure. HIV-1 infection
      should be taken into consideration in children born in countries with a high
      prevalence of HIV, even if they have been living in France for several years and
      present no symptoms.

PMID- 16799799
TI  - Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis
      patients?
AB  - Despite absence of clear proof of efficacy, the use of inhaled corticosteroids
      (ICS) is widespread in cystic fibrosis (CF) patients. Therefore, the effect of
      ICS on lung function and other clinical variables was studied in 27 prepubertal
      CF children with mild to moderate lung disease. In a prospective double-blind
      case-controlled study, fluticasone propionate 500 microg or placebo were
      administered twice daily during 12 months. The mean (standard error of the mean,
      SEM) patient age was 8.2 (0.6) years in the placebo group and 9.0 (0.5) years in
      the fluticasone group. The mean (SEM) forced expiratory volume in 1 s (FEV(1))
      was 91% (4%) in the placebo group and 86% (4%) in the fluticasone group. There
      was no statistically significant difference in the evolution of lung function and
      the number of respiratory exacerbations between groups. However, longitudinal
      growth in fluticasone patients was significantly slower than in placebo patients:
      3.96 (0.29) cm versus 5.49 (0.38) cm [p<0.005, analysis of variance (ANOVA)] over
      the 12-month study duration. This resulted in a significant change in height
      standard deviation score (SDS) of -0.38 (0.09) in the fluticasone group versus 
      0.01 (0.07) in the placebo group (p<0.003, ANOVA). No catch-up growth was noted 1
      2 years after discontinuation of inhaled steroids. The use of high-dose ICS in CF
      patients with mild lung disease may lead to persistent growth impairment.

PMID- 16799800
TI  - Changes in respiratory quinone profiles of enhanced biological phosphorus removal
      activated sludge under different influent phosphorus/carbon ratio conditions.
AB  - Changes in the microbial community of an enhanced biological phosphorus removal
      (EBPR) activated sludge system under different influent phosphorus/carbon (P/C)
      ratio conditions were investigated through evaluation of population respiratory
      quinone profiles. A total of 13 types of respiratory quinone homologs consisting
      of 3 types of ubiquinones (UQ) and 10 types of menaquinones (MK) were identified
      in this study. The dominant quinones were UQ-8 and MK-7 throughout the
      operational period. A higher P/C ratio (0.1) in the influent stimulated an
      increase in the mole fractions of UQ-8, MK-7, MK-8(H(4)), MK-9(H(4)) and MK
      8(H(8)), suggesting that actinobacterial polyphosphate-accumulating organisms
      (PAO) containing partially hydrogenated MK, mainly MK-8(H(4)), were contributing
      to EBPR. However, when the P/C ratio gradually decreased from 0.1 to 0.01, the
      mole fractions of UQ-8 increased from 0.46 to 0.58, while MK-7, MK-8(H(2)), MK
      8(H(4)), MK-9(H(4)), MK-8(H(8)) and MK-9(H(6)) markedly decreased. These changes
      in the respiratory quinone profiles suggest that glycogen-accumulating organisms
      corresponding to some Gammaproteobacteria had become dominant populations with a
      decrease in actinobacterial PAO. On the other hand, increasing abruptly the P/C
      ratio to 0.1 further caused an increase in the mole fraction of UQ-8, indicating
      that Rhodocyclus-related organisms were important PAO.

PMID- 16799801
TI  - A suggested clinical score to predict the severity of adenoid obstruction in
      children.
AB  - Chronic nasal obstruction in children is a very common disorder. Obstructing
      adenoid is usually the first to blame. Though the clinical assessment is
      essential, it is often considered unreliable or insufficient. We conducted a
      prospective clinical study to validate a clinical score predicting the severity
      of adenoid obstruction in symptomatic children. The clinical score (CS) included
      mouth breathing, snoring, restless sleep, frequent waking-up at night and
      obstructive breathing during sleep. Each item received a score of 0 or 1. The
      palatal airway was evaluated on a lateral nasopharyngeal x-ray. The degree of
      obstruction was assessed intra-operatively by a laryngeal mirror using a 3-grade
      scale. The volume of each adenoid specimen was measured. Eighty-six patients were
      enrolled, 51 boys and 35 girls, aged 13-181 months (mean 52, median 45). The CS
      correlated very well with the intra-operative findings (p < 0.01) and with the
      degree of palatal airway obstruction (p < 0.05) but not with the volume of the
      adenoid removed (p > 0.05). The CS was higher in children younger than 3 years
      (CS > 3 in 85.7% vs. 29.2%), having more frequent obstructive breathing during
      sleep (71.43% vs. 21.54%). A CS of three or higher, predicted severe obstruction
      in 96.5% of patients, as detected intra-operatively. The suggested CS is simple
      to use and is highly reliable in identifying children in need for adenoidectomy,
      in the context of normal anterior rhinoscopy and tonsils less than grade three.

PMID- 16799802
TI  - Otomycosis: subdermal growth in calcified mass.
AB  - Reports on clear identification of fungi in subdermal tissue in chronic fungal
      external otitis are rare in recent years. Our patient was an immunocompetent
      adult male with an 8 year history of chronic otitis externa who presented with
      pustules on the external auditory canal (EAC) and necrosis and perforation of the
      tympanic membrane. Type I tympanoplasty was performed, but wound healing was
      delayed and swelling of the EAC occurred. Incision biopsy and staining (Gomori
      Grocott and PAS) revealed fungal hyphae within small, calcified, subepidermal
      masses. A 3 month course of oral itraconazole was effective in healing the
      lesion. Calcification, a rarely reported finding in otomycosis, may represent a
      protective reaction against topical use of antifungal drugs.

PMID- 16799803
TI  - Three cases of organized hematoma of the maxillary sinus.
AB  - Organized hematoma of the maxillary sinus is a rare clinical disease. To our
      knowledge, only a few cases of organized hematoma of the maxillary sinus have
      previously been published, most coming without bleeding history and disorders. We
      report three cases of organized hematoma of the maxillary sinus presenting with
      an enlarging maxillary sinus mass. In the evaluation of a patient with recurrent
      nasal bleeding, nasal obstruction, and an enlarging maxillary mass, organized
      hematoma of the maxillary sinus should be included in the differential diagnosis.

PMID- 16799804
TI  - Laryngeal actinomycosis accompanying laryngeal carcinoma: Report of two cases.
AB  - Actinomycosis is a systemic chronic bacterial infection caused by Actinomyces
      israelii, an anaerobic organism normally resident in the human mouth. It can
      involve any organ, but cervicofacial disease is the most common. Laryngeal
      involvement is rare and usually occurs secondary to the oral, cervical or
      mandibular disease. There are only a few cases of primary laryngeal actinomycosis
      (LA) in the literature. Actinomycosis can also be a complication of head and neck
      surgery. Here we present two cases of LA accompanying laryngeal carcinoma and
      discuss in the literature about this event.

PMID- 16799805
TI  - Counselling of hearing aid users is highly cost-effective.
AB  - Hearing aids (HAs) are often left unused. Several investigations have shown that
      the use of HAs and the skills to use them can be significantly improved through
      counselling. Follow-up counselling is often restricted by increased cost. The
      objective of the study was to assess the cost and the effect of follow-up
      counselling on HA use. In a prospective pre-post design study, 98 first-time HA
      users were counselled 6 months after the fitting of a HA, and the use of and
      benefit from HAs were measured by means of an interview and the short form of the
      hearing handicap inventory for the elderly (HHIE-S) and the EuroQoL (EQ-5D)
      questionnaires. The results obtained before and 6 months after counselling were
      compared and the cost of counselling was calculated. After follow-up counselling,
      over half of the occasional users of a HA and as many as one third of the non
      users became regular users. The number of regular users increased by 16 subjects,
      and non-users decreased from 29 subjects to 17. The HHIE-S results showed a
      significant positive change, but the EQ-5D results showed practically no change.
      The additional expense of follow-up counselling at home was approximately 8.8%
      (83 euro per visit) of the calculated 942 euro cost of fitting a HA. Bringing one
      unused HA into regular use required 508 euro. The results show that HA use and
      the consequent benefit can be significantly increased through counselling. The
      expense caused by follow-up counselling at home is highly acceptable in addition
      to the cost of fitting a HA.

PMID- 16799806
TI  - The positional distribution of cell death of ray parenchyma in a conifer, Abies
      sachalinensis.
AB  - We monitored the distribution of death of secondary xylem cells in a conifer,
      Abies sachalinensis. The cell death of tracheids, which are tracheary elements,
      occurred successively and was related to the distance from cambium. Thus, it
      resembled programmed cell death. By contrast, the death of long-lived ray
      parenchyma cells had the following features: (1) ray parenchyma cells remained
      alive for several years or more; (2) in many cases, no successive cell death
      occurred even within a given radial cell line of a ray; and (3) the timing of
      cell death differed among upper and lower radial cell lines and other lines of
      cells within a ray. These results indicate that the death of long-lived ray
      parenchyma cells involves a different process from the death of tracheids. The
      initiation of secondary wall formation and the lignification of ray parenchyma
      cells in the current year's annual ring were delayed in the upper and lower
      radial cell lines of a ray. In addition, the density of distribution and
      orientation of cortical microtubules in such cells were different from those in
      cells in other radial lines. Ray parenchyma cells in the previous year's annual
      ring within the upper and lower radial cell lines of a ray contained many starch
      grains. Our results indicate that positional information is an important factor
      in the control of the pattern of differentiation and, thus, of the functions of
      ray parenchyma cells that are derived from the same cambial ray cells.

PMID- 16799807
TI  - Agrobacterium tumefaciens-mediated transformation of Rhipsalidopsis gaertneri.
AB  - A protocol for Agrobacterium tumefaciens-mediated genetic transformation of
      Rhipsalidopsis cv. CB5 was developed. Calluses derived from phylloclade explants
      and sub-cultured onto fresh callus induction medium over a period of 9-12 months
      were co-cultivated with A. tumefaciens LBA4404. Plasmid constructs carrying the
      nptII gene, as a selectable marker, and the reporter uidA gene were used.
      Transformed Rhipsalidopsis calluses with a vigorous growth phenotype were
      obtained by extended culture on media containing 600 mg l(-1) kanamycin. After 9
      months of a stringent selection pressure, the removal of kanamycin from the final
      medium together with the culture of the transformed calluses under nutritional
      stress led to the formation of several transgenic adventitious shoots.
      Transformation was confirmed by GUS staining (for uidA gene), ELISA analysis and
      Southern blot hybridization (for the nptII gene). With this approach, a
      transformation efficiency of 22.7% was achieved. Overall results described in
      this study demonstrate that Agrobacterium-mediated transformation is a promising
      approach for this cactus species.

PMID- 16799808
TI  - Genetic mapping reveals a single major QTL for bacterial wilt resistance in
      Italian ryegrass (Lolium multiflorum Lam.).
AB  - Bacterial wilt caused by Xanthomonas translucens pv. graminis (Xtg) is a major
      disease of economically important forage crops such as ryegrasses and fescues.
      Targeted breeding based on seedling inoculation has resulted in cultivars with
      considerable levels of resistance. However, the mechanisms of inheritance of
      resistance are poorly understood and further breeding progress is difficult to
      obtain. This study aimed to assess the relevance of the seedling screening in the
      glasshouse for adult plant resistance in the field and to investigate genetic
      control of resistance to bacterial wilt in Italian ryegrass (Lolium multiflorum
      Lam.). A mapping population consisting of 306 F1 individuals was established and
      resistance to bacterial wilt was assessed in glasshouse and field experiments.
      Highly correlated data (r = 0.67-0.77, P < 0.01) between trial locations
      demonstrated the suitability of glasshouse screens for phenotypic selection.
      Analysis of quantitative trait loci (QTL) based on a high density genetic linkage
      map consisting of 368 amplified fragment length polymorphism (AFLP) and simple
      sequence repeat (SSR) markers revealed a single major QTL on linkage group (LG) 4
      explaining 67% of the total phenotypic variance (Vp). In addition, a minor QTL
      was observed on LG 5. Field experiments confirmed the major QTL on LG 4 to
      explain 43% (in 2004) to 84% (in 2005) of Vp and also revealed additional minor
      QTLs on LG 1, LG 4 and LG 6. The identified QTLs and the closely linked markers
      represent important targets for marker-assisted selection of Italian ryegrass.

PMID- 16799809
TI  - An integrated SSR map of grapevine based on five mapping populations.
AB  - A grapevine (mainly Vitis vinifera L., 2n = 38) composite genetic map was
      constructed with CarthaGene using segregation data from five full-sib populations
      of 46, 95, 114, 139 and 153 individuals, to determine the relative position of a
      large set of molecular markers. This consensus map comprised 515 loci (502 SSRs
      and 13 other type PCR-based markers), amplified using 439 primer pairs (426 SSRs
      and 13 others) with 50.1% common markers shared by at least two crosses. Out of
      all loci, 257, 85, 74, 69 and 30 were mapped in 1, 2, 3, 4 and 5 individual
      mapping populations, respectively. Marker order was generally well conserved
      between maps of individual populations, with only a few significant differences
      in the recombination rate of marker pairs between two or more populations. The
      total length of the integrated map was 1,647 cM Kosambi covering 19 linkage
      groups, with a mean distance between neighbour loci of 3.3 cM. A framework
      integrated map was also built, with marker order supported by a LOD of 2.0. It
      included 257 loci spanning 1,485 cM Kosambi with a mean inter-locus distance of
      6.2 cM over 19 linkage groups. These integrated maps are the most comprehensive
      SSR-based maps available so far in grapevine and will serve either for choosing
      markers evenly scattered over the whole genome or for selecting markers that
      cover particular regions of interest. The framework map is also a useful starting
      point for the integration of the V. vinifera physical and genetic maps.

PMID- 16799810
TI  - Differential TCR gene usage between WC1- and WC1+ ruminant gammadelta T cell
      subpopulations including those responding to bacterial antigen.
AB  - Ruminant gammadelta T cells are divided into subpopulations based on the presence
      or absence of WC1 co-receptors (scavenger-receptor-cysteine-rich family members
      uniquely expressed on gammadelta T cells). Evidence suggests WC1+ are
      inflammatory while WC1- are regulatory and that they also differ in their tissue
      distribution. Recently, this paradigm was refined further as cells that produce
      interferon-gamma and proliferate to autologous antigens, leptospira antigens, or
      IL-12 were largely found within the WC1+ subpopulation that bears the WC1.1
      antigenic epitope but not that bearing the WC1.2 epitope. Here, the T cell
      receptor gene expression by these different subpopulations (WC1-, WC1.1+, and
      WC1.2+) was compared using flow cytometrically-purified cells and reverse
      transcriptase-polymerase chain reaction (RT-PCR). The WC1- gammadelta T cells had
      transcripts for all 11 possible combinations of the TRG subgroup V and C genes
      while those in both WC1+ subpopulations were restricted to TRGV3-TRGC5 and TRGV7
      TRGC5. In contrast, all three subpopulations expressed transcripts from all four
      known bovine TRDV genes. Further analysis of the WC1+ gammadelta T cells that
      proliferated in leptospira antigen-stimulated cultures indicated that they do not
      represent a unique subpopulation within the larger WC1+ population based on their
      TCR gene usage. Moreover, sequencing of 65 transcripts showed that their
      junctional regions were diverse as TRGJ5-1, TRGJ5-2, TRDJ1, and TRDJ3 were used,
      and CDR3s ranged from 9 to 24 amino acids. The restricted but shared gammadelta
      TCR gene usage for WC1.1+, WC1.2+, and WC1(+)-antigen-responsive cells leaves
      open the possibility that the WC1 co-receptor is an important determining element
      in the activation process and subsequent response.

PMID- 16799812
TI  - Irinotecan changes gene expression in the small intestine of the rat with breast
      cancer.
AB  - PURPOSE: The aetiology of mucositis is complex involving change in gene
      expression, altered apoptosis and interaction between epithelial and
      subepithelial compartments. This is the first investigation using microarray to
      assess chemotherapy-induced changes in the gut. The aims of this study were to
      identify genes that are altered by irinotecan, to determine how these genes
      contribute to apoptosis and to identify any potential gene families and pathways
      that are important for mucositis development. METHODS: Tumour-bearing female dark
      Agouti rats were administered twice with 150 mg/kg of irinotecan and killed 6 h
      after the final dose. Jejunal tissue was harvested and RNA was isolated. cDNA was
      synthesised and purified, prior to hybridisation and microarray analysis. A 5-K
      oligo clone set was used to investigate gene expression. Results from the
      microarray were quantified using RT-PCR. RESULTS: Many genes were significantly
      up- or down-regulated by irinotecan. In particular, multiple genes implicated in
      the mitogen-activated protein kinase (MAPK) signalling pathway were
      differentially regulated following treatment. These included interleukin 1
      receptor, caspases, protein kinase C and dual-specificity phosphatase 6. RT-PCR
      was used to confirm effects of irinotecan on caspase-1 expression in jejunal
      tissue and was significantly increased 6 h after treatment with irinotecan.
      CONCLUSIONS: This study has identified MAP kinase signalling as being involved
      with irinotecan-induced intestinal damage and confirms previous findings with
      radiation-induced oral mucosal damage, which also implicated this pathway.
      Microarrays are emerging as a valuable tool in mucositis research by linking such
      findings. The common pathway of chemotherapy- and radiotherapy-induced damage,
      which utilises the caspase-cascade, may be a useful target to prevent apoptosis
      following cancer treatment.

PMID- 16799813
TI  - Procamallanus (Spirocamallanus) anguillae sp. n. (Camallanidae) and some other
      nematodes from the Indonesian shortfin eel Anguilla bicolor in Thailand.
AB  - A new species of parasitic nematode, Procamallanus (Spirocamallanus) anguillae
      sp. n. (family Camallanidae), is described based on specimens recovered from the
      intestine of the Indonesian eel Anguilla bicolor McClelland (type host) from
      southern Thailand (type locality Phuket Island). It is characterized mainly by
      the presence of 10-13 spiral ridges in the buccal capsule, length of spicules
      (366-372 microm and 198-216 microm), presence of a gubernaculum, arrangement of
      caudal papillae, and by the broad female tail with a digit-like projection
      bearing two cuticular spikes. In addition, two species of larval nematodes,
      Physalopteridae gen. sp. and Anisakis cf. simplex (Rudolphi 1809), were recorded
      from A. bicolor. All species are briefly described and illustrated.

PMID- 16799811
TI  - Cisplatin's tumoricidal effect on human breast carcinoma MCF-7 cells was not
      attenuated by American ginseng.
AB  - PURPOSE: We previously observed that American ginseng berry and ginsenoside Re
      attenuated cisplatin-induced emesis in a rat model, suggesting that the herb may
      have a value in treating chemotherapy-induced nausea/vomiting. However, it is not
      clear whether consuming ginseng concurrently with chemotherapy affects the
      efficacy of chemotherapeutic agents. In this study, we explored if the ginseng
      extract and its constituents, ginsenosides Rb1, Rb3, and Re, alter tumoricidal
      activity of cisplatin in human cancer cells. METHODS: Tumoricidal effects of
      cisplatin, and/or American ginseng berry extract (AGBE) and ginsenosides Rb1,
      Rb3, and Re, on human breast carcinoma MCF-7 cells were measured as cell
      proliferation in vitro. Cell counts were performed in MCF-7 cells pretreated with
      test agents for 72 h. RESULTS: Cisplatin decreased MCF-7 cell proliferation
      significantly in a concentration-dependent manner. Compared to control group,
      cisplatin reduced the cell proliferations to 56.5+/-3.3% at 1 microg/ml, to
      36.6+/-2.4% at 5 microg/ml, and to 26.9+/-2.4% at 15 microg/ml (P<0.01). AGBE
      also inhibited the cell proliferation significantly, although in a less extended
      manner. When the berry extract at 0.5 mg/ml was used with cisplatin at 1
      microg/ml, a significant enhancement of cisplatin's activity was observed (35.8+/
      2.5%; P<0.05). We also observed that Rb1 did not change cisplatin's activity;
      Rb3, at a higher concentration, increased cisplatin's anti-proliferation activity
      (48.0+/-1.2%; P<0.05); Re increased cisplatin's activity (Re 0.1 mg/ml, 48.0+/
      2.8%; Re 0.3 mg/ml, 31.9+/-2.2%, P<0.01). CONCLUSION: Our data suggest that AGBE
      and the tested ginsenosides do not attenuate cisplatin's tumoricidal activity in
      MCF-7 cells, but in fact may actually enhance it. Additionally, the ginseng
      extract and ginsenoside Re by themselves exerted anti-proliferative activity
      against MCF-7 cells. The herb might potentially serve a complementary role with
      the chemotherapeutic agents in treating cancer, in addition to decreasing
      chemotherapy-induced nausea/vomiting.

PMID- 16799814
TI  - [Maximilian Koenigsbeck and localized pustular psoriasis].
AB  - In 1917, Maximilian Koenigsbeck in his thesis first described a localized type of
      pustular psoriasis confined to the hands and feet. That was the starting point
      for the development of the eponym "Koenigsbeck-Barber" disease for psoriasis
      pustulosa palmaris et plantaris. The present paper is the first report dealing
      with the life and work of Koenigsbeck. It includes a short biography, a
      discussion of Koenigsbeck's thesis in its historical context and the history of
      the eponym with emphasis on its current significance.

PMID- 16799815
TI  - A common coding framework in self-other interaction: evidence from joint action
      task.
AB  - Many of our actions are influenced by the social context. Traditional approach
      attributes the influence of the social context to arousal state changes in a
      socially promotive way. The ideomotor approach, which postulates common coding
      between perceived events and intended actions, uses a conceptual scheme of
      ideomotor compatibility to explain self-other interaction. In this study, we
      recorded reaction times (RTs) and event-related potentials in a Go/NoGo task with
      stimulus-response (S-R) compatibility arrangement to examine how the social
      context affects self-other interaction. Although the social facilitation theory
      predicted that RTs would be faster when acting together with audience rather than
      acting alone, the ideomotor theory predicted S-R compatibility effects only for
      the joint condition. The results revealed S-R compatibility on the RTs,
      lateralized readiness potential of the Go trials, and P3 of the NoGo trials in
      the joint condition, which were in line with the predictions of the ideomotor
      theory. Owing to the anticipation of other's actions, self and other's actions
      are internally and unintentionally coded at the representational level and their
      functional equivalency can be realized through a common coding framework between
      perception and action systems. Social facilitation theory was not supported,
      because we found no significant data differences depending on the setting.

PMID- 16799816
TI  - Effect of altered pre-exercise carbohydrate availability on selection and
      perception of effort during prolonged cycling.
AB  - This study assessed the effect of altered carbohydrate (CHO) availability on self
      selected work rate during prolonged time-trial cycling. Eight endurance-trained
      men undertook two experimental cycling time-trials after glycogen-depleting
      exercise and 2 days of: (a) high (9.3 +/- 0 g CHO kg(-1) day(-1)) (HC) and (b)
      low CHO intakes (0.6 +/- 0.1 g CHO kg(-1) day(-1)) (LC), via a double-blinded
      crossover design. All feedback regarding performance was removed during both
      exercise trials. Self-selected external power output was not different during the
      first 2 h of exercise between experimental conditions (P > 0.05), despite
      reported sensations of increased tiredness before and during exercise,
      significantly reduced whole body CHO oxidation (P < 0.05), plasma lactate
      concentrations (P < 0.05) and earlier onset of fatigue during exercise in LC
      versus HC. Perceived exertion was not different throughout exercise between
      conditions (P > 0.05). Mean power output declined significantly in LC versus HC
      (P < 0.05) after approximately 2 h of exercise, and was associated with
      significant reductions in cadence, heart rate and plasma glucose concentration (P
      < 0.05). These results demonstrate that when compared with time-trial cycling
      performed after a HC diet, reduced CHO availability does not initially alter self
      selected work rate in endurance athletes who are deceived of their CHO status
      prior to exercise. This finding suggests that reduced work rate during exercise
      following lowered CHO intake may, in part, be a consequence of the subject's
      awareness of dietary CHO restriction rather than solely a physiologically
      mediated action. Further research is required to distinguish the influence of
      circulating glucose and peripheral glycogen availability on pacing strategy
      during prolonged exercise.

PMID- 16799817
TI  - Physiological responses to nordic walking, walking and jogging.
AB  - The goal of this study was to evaluate the physiological responses during
      incremental field tests (FT) in nordic walking (NW), walking (W) and jogging (J).
      Fifteen healthy middle-aged women participated in three FT. Heart rate (HR) and
      oxygen uptake (V(O)(2)) were monitored continuously by portable analyzers.
      Capillary blood lactate (La) was analyzed at rest and after every stage of the
      FT. The disciplines showed differences during stage 1.8 and 2.1 m s(-1) for
      V(O)(2) between NW and W (P < 0.05). The maximum value was measured at 1.8 m s(-1
      )(8%). In accordance with La, V(CO)(2) was higher in NW compared with W during
      all stages (P < 0.05) and even higher in NW compared with J during 2.1 and 2.4 m
      s(-1). While there were higher HR for NW and W at 2.4 m s(-1) than in J (P <
      0.01), there were increases for HR at fixed values of 2 (La2) and 4 (La4) mmol l(
      1 )lactate for J compared with NW and W (P < 0.01). Although the speed of NW was
      slower than that of W at La2 and La4 (P < 0.05), there were no differences for
      the HR and the V(O)(2) Our results demonstrate that metabolic responses are a
      helpful instrument to assess the intensity during bipedal exercise. As NW speed
      at submaximal lactate levels is lower than in W and J, W and J test measures of
      HR and V(O)(2) are not suitable for NW training recommendations. Additionally,
      the V(O)(2) formed by performing NW is not as high as previously reported.

PMID- 16799818
TI  - Plasma Hsp72 is higher in runners with more serious symptoms of exertional heat
      illness.
AB  - Exertional heat illness is a potentially fatal disorder that primarily affects
      fit young men. Plasma Hsp72 may be important in the aetiology of this disorder,
      acting as a danger signal to the organism and leading to an inflammatory
      response. The aim of this study was to determine whether patients with exertional
      heat illness following a 14 km run show a difference in their plasma Hsp72
      concentration compared with control subjects who completed the event without
      incident. Patients (n = 22) and controls (n = 7) were all male. The patients were
      subdivided into two groups, one of which exhibited more serious symptoms
      indicating neurological impairment such as confusion (n = 13) (CNS) while the
      other group exhibited mild symptoms (MILD) (n = 9). The CNS group had a higher
      rectal temperature (T(rec)) compared with the control group (41.0 +/- 0.3 vs.
      39.8 +/- 0.2 degrees C, P < 0.05, mean +/- SE). Immediately after the run plasma
      Hsp72 was higher in the CNS group compared to controls and patients with mild
      symptoms (37.9, 17.0, and 20.9 ng/ml, respectively, P < 0.005). There was a
      correlation between plasma Hsp72 and T(rec) measured immediately after the race
      (r = 0.597, P < 0.001, n = 29). However, core temperature was not the only factor
      leading to increased plasma Hsp72 immediately post race. Plasma Hsp72 was still
      higher in CNS patients compared with the control group (P < 0.05) when T(rec )was
      included as a covariate. In conclusion, plasma Hsp72 was elevated immediately
      after a 14 km run with higher levels in patients with more serious symptoms of
      heat illness.

PMID- 16799819
TI  - Adaptations to endurance training in the healthy elderly: arm cranking versus leg
      cycling.
AB  - The effect in healthy elderly subjects of cycle ergometer or arm ergometer
      training on peak oxygen consumption (VO(2peak)) and ventilatory threshold (VT)
      was studied. The aim was to determine the benefit of each training modality on
      specific and cross exercise capacity. The cross-effect was also evaluated as an
      index of the central nature of the adaptive response to training. Twelve non
      smoking healthy males (age: 67 +/- 5 year; body mass: 75 +/- 9 kg) were randomly
      divided in two age-matched groups of six, performing an arm cranking (ARM) or a
      cycloergometer (CYC) training (12-week, 30 min, 3 times/week), while a third
      group of 6 subjects (age: 73 +/- 4 year; body mass: 80 +/- 8 kg) performed no
      training (control, C). At baseline and following the intervention, subjects
      carried out an incremental test to exhaustion both on the ergometer on which they
      trained (specific test) and on the other ergometer (cross test). Respiratory
      variables were measured breath by breath and heart rate (HR) was recorded. Peak
      oxygen consumption (VO(2peak)), ventilation (VE(peak)), oxygen pulse (O2P(peak))
      and heart rate (HR(peak)) were averaged over the last 10 s of exercise. Following
      training, while HR(peak) remained unchanged, significantly higher W(peak),
      VO(2peak), VE(peak) and O2P(peak) were obtained in both training groups, on both
      ergometers. The amplitude of the increase in W(peak), VO(2peak) and O2P(peak) was
      significantly higher for specific than for cross tests ( approximately 19% vs.
      approximately 8 % in CYC; approximately 22% vs. approximately 9% in ARM, P <
      0.01) while the increase in same test condition was similar. No change was
      observed in the C group. The results indicate that aerobic training brought about
      with different muscle masses, produce similar improvements in maximal and
      submaximal exercise capacity. Roughly half of such improvements are specific to
      exercise mode, which suggests peripheral adaptations to training. The other half
      is non-specific since it influences also the alternative exercise modality, and
      is probably due to central adaptations.

PMID- 16799820
TI  - Novel deoxycytidine kinase gene polymorphisms: a population screening study in
      Caucasian healthy volunteers.
AB  - INTRODUCTION: Deoxycytidine kinase (DCK) is the rate-limiting enzyme of the
      intracellular phosphorylation of nucleoside anticancer drugs, including
      gemcitabine and beta-arabinofuranosylcytosine, to their active triphosphates.
      This study was performed to assess the occurrence and frequency of DCK
      polymorphisms in a predominantly Caucasian population and to choose candidate
      polymorphisms for subsequent functionality studies. METHODS AND MATERIALS: All
      seven DCK exons and the promoter region were sequenced from 100 healthy
      volunteers (79 females and 21 males). With respect to ethnicity, the study cohort
      comprised 93 Caucasian, one Asian, one African, and five mixed-race individuals.
      RESULTS: Six novel single nucleotide polymorphisms (SNPs) were found (-243G>T, 
      135G>C, 261G>A, 364C>T, 727A>C, IVS6+41T>A). Two SNPs are nonsynonymous and lead
      to changes in the amino acid sequence [C364T in exon 3 (P121S) and A727C in exon
      6 (K242Q)]. The presence of the linked promoter polymorphism -360C>G/-201C>T was
      confirmed in Caucasians, but was less frequent than what has been reported from
      Asians (allele frequencies 2 versus 15.6%). The most prevalent haplotype was the
      wild-type plus IVS6+41TT (85.8%). This study found novel DCK polymorphisms,
      including nonsynonymous SNPs, in exons 3 and 6. A comparison of the data obtained
      in this study with those reported in a previous study on Asians [Shi et al.
      (2004) Pharmacogenetics 14:759-768] illustrates marked inter-ethnic differences
      in the occurrence and frequency of DCK polymorphisms. CONCLUSION: The higher
      allelic frequency of the promoter polymorphism -C360G/-C201T in Asians than in
      Caucasians might predispose Asians to nucleoside drug-associated toxicity. These
      data will be used to assess the effect of DCK candidate SNPs (promoter, exons 3
      and 6) in patients receiving gemcitabine anticancer treatment.

PMID- 16799822
TI  - Environmental monitoring of occupational exposure to N,N-dimethylformamide:
      comparison between active and diffusive sampling.
AB  - OBJECTIVES: The objective of this study is to optimize the evaluation of the
      exposure to N,N-dimethylformamide (DMF) in synthetic leather factories by
      diffusive samplers. The DMF exposure was monitored in synthetic leather factories
      by two sampler types: active and diffusive. METHODS: Air measurements were
      carried out using two different personal air samplers, a diffusive and an active
      one. The diffusive sampling method, TK200 with charcoal filters, was examined in
      comparison with pumping through NIOSH silica gel tubes workplace air as with the
      currently available "gold standard". The evaluation was carried out, in two
      different years but in the same season, for all the duration of the shift, i.e. 8
      h on workers employed in five different factories in the district of Florence and
      Prato (Italy). RESULTS: The statistical and graphical analysis of data show a
      good correlation between active and passive samplers (r = 0.96, P < 0.001, n =
      91), a good linear regression (DMF(diffusive )= 0.95 DMF(active) + 0.15, R (2) =
      0.92), a not statistically significant difference between data (tested by paired
      t test and non-parametric Wilcoxon test). Moreover, all these results are
      confirmed for data lower and higher than TLV-TWA, in particular we found a
      significant Pearson correlation (r = 0.92, P < 0.001, n = 83; r = 0.92, P < 0.05,
      n = 8, respectively) and a significant linear regression (DMF(diffusive )= 0.88
      DMF(active) + 0.73, R (2 )= 0.86; DMF(diffusive )= 0.90 DMF(active) + 3.76, R (2
      )= 0.85). Besides, the analysis of graphical representations confirmed the
      previous evidences. Finally, we can not find a significant difference between
      different types of job. CONCLUSIONS: Due to the good agreement between the two
      groups of data, the TK200 samplers can be considered as a simpler approach than
      the pump for screening worker exposures to DMF.

PMID- 16799821
TI  - Functional neuroimaging in the preoperative evaluation of children with drug
      resistant epilepsy.
AB  - FUNCTIONAL NEUROIMAGING: Although the primary imaging modality in the management
      of epilepsy is magnetic resonance imaging MRI, functional neuroimaging with
      positron-emission tomography (PET) and single photon emission computed tomography
      (SPECT) often provides complementary information and, in a number of situations,
      provides unique information that cannot be obtained with MRI. The most commonly
      used PET tracers used for epilepsy evaluation are 2-deoxy-2-[(18)F]fluoro-D: 
      glucose (FDG) and [(11)C]flumazenil (FMZ). Recently, interictal PET with alpha
      [(11)C]methyl-L: -tryptophan was found to be highly specific for the epileptic
      focus and can differentiate between epileptogenic and nonepileptogenic lesions in
      the same patient (e.g., in patients with tuberous sclerosis). DISCUSSION: In this
      review, we discuss clinical applications of these three PET tracers in drug
      resistant temporal and extratemporal lobe epilepsy, selected epilepsy syndromes
      of childhood, lesional and nonlesional epilepsy, and the challenges of imaging
      secondary epileptic foci. A brief discussion of SPECT applications in epilepsy is
      also included. With further development of new tracers highly sensitive and
      specific for epileptogenic brain regions, the presurgical evaluation of
      refractory epilepsy will be greatly facilitated. Approximately 0.5 to 1.0% of the
      population suffer from epilepsy, of which 15-20% are intractable. Infants and
      children, whose seizures have a focal onset are refractory to anticonvulsants and
      are prolonged, tend to have the worst cognitive outcome [Meador KJ, Neurology 58
      (Suppl 5):S21-S26, 2002]. Seizures themselves affect the developing brain and
      contribute to an adverse neurologic outcome (Holmes, Pediatric Neurology 33:1
      110, 2005). CONCLUSION: Therefore, in treating children with intractable
      epilepsy, it is important to consider seizure control and to give allowance for
      normal cognitive development.

PMID- 16799823
TI  - Risk factors and musculoskeletal complaints in non-specialized nurses, IC nurses,
      operation room nurses, and X-ray technologists.
AB  - OBJECTIVES: To gain more insight into the prevalence rates of musculoskeletal
      complaints of neck-shoulder and low back and to determine the relation between
      physical and psychosocial work-related risk factors and the complaints mentioned
      in non-specialized nurses, operation room nurses, Intensive Care (IC) nurses and
      X-ray technologists. METHODS: The study population consists of 3,169 employees
      affiliated to eight university hospitals in the Netherlands. The study was
      conducted using a cross-sectional survey design. The parameters under study were
      having or having had (severe) low back or neck-shoulder complaints during the
      past year. In logistic regression analyses odds ratio's and CI 95% were estimated
      for all relevant risk factors for each of the four professional groups. RESULTS:
      In all groups prevalence rates of musculoskeletal complaints were high: low back
      76%, neck-shoulder 60%. Operation room nurses perceived more neck-shoulder
      complaints (12 months prevalence) than non-specialized nurses and IC nurses
      perceived less severe low back complaints than non-specialized nurses. Four
      physical risk factors and one psychosocial factor were associated with low back
      complaints in all groups. CONCLUSIONS: The results of the present study indicate
      that both low back complaints and neck-shoulder complaints are major health
      problems in the four professional groups under study. The prevalence rate of neck
      shoulder complaints in operation room nurses is higher than in non-specialized
      nurses and IC nurses, the latter groups having high prevalence rates already. The
      exposure to risk factors is perceived differently by each of the professional
      groups. The professional groups under study all are target for preventive
      interventions; these interventions need to be specified for each of the
      professional groups.

PMID- 16799824
TI  - Stress radiography to measure posterior cruciate ligament insufficiency: a
      comparison of five different techniques.
AB  - Stress radiography presents the golden standard to quantify posterior laxity in
      posterior cruciate ligament (PCL) insufficiency. Several different techniques are
      currently available, but comparative data are insufficient. Different stress
      radiographic techniques result in different values for posterior laxity.
      Comparative controlled clinical study was designed. Prior to PCL reconstruction
      30 patients underwent a series of stress radiographs: Telos device, hamstring
      contraction, kneeling view, gravity view, and an axial view. Posterior
      displacement, side-to-side difference (SSD), condyle rotation, required time, and
      pain were measured. Posterior displacement was: Telos 12.7 +/- 3 mm (SSD 10.6 +/-
      3.1 mm), hamstring contraction 11.2 +/- 3.2 mm (SSD 8.5 +/- 3.4 mm), kneeling
      14.4 +/- 3.8 mm (SSD 10.2 +/- 3.5 mm), gravity view 10.5 +/- 2.8 mm (SSD 9.1 +/-
      2.4 mm), and axial view 19.4 +/- 6.9 mm (SSD 8.5 +/- 4.1 mm). In comparison to
      Telos the hamstring contraction, gravity, and the axial view underestimated the
      SSD by approximately 2 mm. Telos and kneeling caused significantly more pain than
      all other techniques (P < 0.001). The axial view was fastest (115 s, P < 0.001)
      and Telos longest (305 s, P < 0.001), respectively. Telos indicated the lowest
      rotational error with a significant difference between kneeling and gravity (P <
      0.003). In contrast to Telos as the golden standard, hamstring contraction,
      gravity, and axial view underestimated the SSD. Kneeling and Telos are comparable
      with respect to SSD and pain. Although kneeling indicates a greater rotational
      error than Telos, it seems to be a reliable alternative for quantifying posterior
      tibial displacement in a more simple and fast way.

PMID- 16799825
TI  - Temporal change of joint position sense after posterior cruciate ligament
      reconstruction using multi-stranded hamstring tendons.
AB  - A total of 29 patients who had undergone posterior cruciate ligament (PCL)
      reconstruction using multi-stranded hamstring tendons were prospectively followed
      up for joint stability and proprioceptive function at a minimum of 24 months
      after surgery. We measured temporal changes of the posterior laxity by stress
      radiography and the KT-2000 arthrometer, and we also measured joint position
      sense for an average of 42 months (range 24-78 months). In terms of results,
      improvement of joint stability was observed postoperatively and maintained over 2
      years after PCL reconstruction, although posterior stability in the reconstructed
      knee was not identical to the contralateral normal knee. Although joint position
      sense worsened just after reconstruction, it gradually recovered from 18 months
      after surgery. However, proprioceptive function after PCL reconstruction did not
      recover to the same level as in the contralateral normal knee even over 24 months
      after surgery.

PMID- 16799827
TI  - Chondrolysis of the glenohumeral joint following arthroscopic capsular release
      for adhesive capsulitis: a case report.
AB  - This is a case of glenohumeral chondrolysis, following arthroscopy for adhesive
      capsulitis of the shoulder, during which, capsular release has been performed
      using a bipolar radio frequency energy probe. Heat produced during the procedure
      by the radio frequency energy probe, probably was the reason behind the occurance
      of such a rare pathological entity. Chondrolysis has to be put on the top of the
      list of complications that may occur following arthroscopy, whenever radio
      frequency energy tools are used. This is not because it is a common one, but
      because of the difficulty in managing it.

PMID- 16799826
TI  - Augmentation technique with semitendinosus and gracilis tendons in chronic
      partial lesions of the ACL: clinical and arthrometric analysis.
AB  - Most of the techniques described in the literature for the repair of chronic
      partial ACL tears, don't spare the intact portion of the ligament. The aim of
      this study was to perform a prospective analysis of the results of augmentation
      surgery using gracilis and semitendinosus tendons to treat partial sub-acute
      lesions of the ACL. This technique involves an "over the top" femoral passage,
      which enables salvage and strengthening of the intact portion of the ACL. The
      study included 47 patients treated consecutively at our institute from 1993 to
      1998, with a mean injury-surgery interval of 18 weeks (range 12-36). The patients
      were followed up by clinical and instrumental assessment criteria at 3 months, 1
      and 5 years after surgery. Clinical assessment was performed using the IKDC form.
      Subjective and functional parameters were assessed by the Tegner activity scale.
      Instrumental evaluation was done using the KT-2000 instrument: the 30-pound
      passive test and the manual maximum displacement test were performed. We obtained
      good or excellent results in 95.7% of cases. No recurrences in ligamentous laxity
      were observed. We believe that the described technique has the advantage of being
      compatible with ACL anatomy, and enables very rapid functional recovery.

PMID- 16799828
TI  - Arthroscopic anterior cruciate ligament reconstruction with quadriceps tendon
      autograft: clinical outcome in 4-7 years.
AB  - Surgical reconstruction of the anterior cruciate ligament (ACL) is indicated in
      the ACL-deficient knee with symptomatic instability and multiple ligaments
      injuries. In the present study, we describe the clinical results of quadriceps
      tendon-patellar bone autograft for ACL reconstruction. From 1996 to 1998, the
      graft has been used in 38 patients. Thirty-four patients with complete final
      follow-up for 4-7 years were analyzed. The average follow-up time was 62 (48-84)
      months. Thirty-two patients (94%) achieved good or excellent results by Lysholm
      knee rating. Twenty-six patients (76%) could return to moderate or strenuous
      activity after reconstruction. Twenty-eight patients (82%) had ligament laxity of
      less than 2 mm. Finally; 31 patients (91%) were assessed as normal or nearly
      normal rating by IKDC guideline. Twenty-five patients (73%) had less than 10 mm
      difference in thigh girth between their reconstructed and normal limbs. Thirty
      two (94%) and 31 (91%) patients could achieve recovery of the extensor and flexor
      muscle strength in the reconstructed knee to 80% or more of normal knee strength,
      respectively. A statistically significant difference exists in thigh girth
      difference, extensor strength ratio, and flexor strength ratio before and after
      reconstruction. Tunnel expansion with more than 1 mm was identified in 2 (6%)
      tibial tunnels. Our study revealed satisfactory clinical subjective and objective
      results at 4-7 years follow-up. Quadriceps tendon autograft has the advantage of
      being self-available, relatively easier arthroscopic technique, and having a
      suitable size, making it an acceptable graft choice for ACL reconstruction. There
      is little quadriceps muscle strength loss after quadriceps harvest. A quadriceps
      tendon-patellar autograft is an adequate graft choice to ACL reconstruction.

PMID- 16799829
TI  - Computational simulations of the human magneto- and electroenterogram.
AB  - Many functional pathologies of the small intestine are difficult to diagnose
      clinically without an invasive surgical intervention. Often such conditions are
      associated with a disruption of the normal electrical activity occurring within
      the musculature of the small intestine. The far field electrical signals on the
      torso surface arising from the electrical activity within the small intestine
      cannot be reliably measured. However, it has been shown that abnormal electrical
      activity in the small intestine can be distinguished by recording the magnetic
      fields of intestinal origin immediately outside the torso surface. We have
      developed an anatomically-based computational model to simulate slow wave
      propagation in the small intestine, the resulting cutaneous electrical field and
      the magnetic field outside the torso. Using both a one-dimensional and a three
      dimensional model of the duodenum we investigate the degree of detail that is
      required to realistically simulate this far field activity. Our results indicate
      that some of the qualitative behavior in the far field activity can be replicated
      using a one-dimensional model, although there are clear situations where the
      greater level modeling detail is required.

PMID- 16799830
TI  - Computational approach to estimating the effects of blood properties on changes
      in intra-stent flow.
AB  - In this study various blood rheological assumptions are numerically investigated
      for the hemodynamic properties of intra-stent flow. Non-newtonian blood
      properties have never been implemented in blood coronary stented flow
      investigation, although its effects appear essential for a correct estimation and
      distribution of wall shear stress (WSS) exerted by the fluid on the internal
      vessel surface. Our numerical model is based on a full 3D stent mesh. Rigid wall
      and stationary inflow conditions are applied. Newtonian behavior, non-newtonian
      model based on Carreau-Yasuda relation and a characteristic newtonian value
      defined with flow representative parameters are introduced in this research. Non
      newtonian flow generates an alteration of near wall viscosity norms compared to
      newtonian. Maximal WSS values are located in the center part of stent pattern
      structure and minimal values are focused on the proximal stent wire surface. A
      flow rate increase emphasizes fluid perturbations, and generates a WSS rise
      except for interstrut area. Nevertheless, a local quantitative analysis discloses
      an underestimation of WSS for modelisation using a newtonian blood flow, with
      clinical consequence of overestimate restenosis risk area. Characteristic
      viscosity introduction appears to present a useful option compared to rheological
      modelisation based on experimental data, with computer time gain and relevant
      results for quantitative and qualitative WSS determination.

PMID- 16799831
TI  - Cognitive and clinical predictors of work outcomes in clients with schizophrenia
      receiving supported employment services: 4-year follow-up.
AB  - In a prior study we showed that cognitive functioning was a modest predictor of
      work and supported employment services over 2-years in 30 clients with
      schizophrenia, whereas symptoms were not (McGurk et al. (2003). Psychiatric
      Services, 58, 1129-1135). In order to evaluate whether the long-term provision of
      supported employment services reduced the impact of cognitive functioning on
      work, we examined the relationships between cognitive functioning and symptoms
      assessed after the initial 2 years of the program, and work and vocational
      services over the following 2 years (3-4 years after joining the program).
      Cognitive functioning was more predictive of work during the latter 2 years of
      the study than the first 2 years, and a similar but weaker pattern was present
      for the prediction of employment services. Symptoms remained weak predictors for
      both time periods. In addition, learning and memory and executive functions were
      strongly correlated with job task complexity during the 3-4 year follow-up, but
      not the 1-2 year follow-up, suggesting that employment specialists were able to
      improve their ability to match clients to jobs based on their cognitive skills.
      Furthermore, the specific associations between cognitive functioning, services,
      and work outcomes changed from years 1-2 to years 3-4, suggesting a dynamic
      interplay between these factors over the long-term, rather than static and
      unchanging relationships. The findings indicate that rather than supported
      employment services reducing the impact of cognitive functioning on long-term
      competitive work, the impact actually increases over time, suggesting that
      efforts to improve cognitive functioning (e.g., cognitive rehabilitation) may
      optimize employment outcomes in schizophrenia.

PMID- 16799832
TI  - Comparison of self-report and clinician-rated measures of psychiatric symptoms
      and functioning in predicting 1-year hospital readmission.
AB  - This study compared the self-report Behavior and Symptom Identification Scale
      (BASIS-32) and clinician-rated Global Assessment of Functioning (GAF) in their
      ability to predict a measure of psychiatric outcome, 1-year psychiatric hospital
      readmission. BASIS-32 and GAF were completed at admission for 1034 patients in an
      inpatient psychiatric facility. Multiple informants analysis was used to
      determine the difference between the two in predicting readmission within 1 year.
      We also examined sensitivity, specificity, and predictive value positive of the
      two measures, and whether self-report added information above clinician rating in
      predicting outcome. While the odds of 1-year readmission decreased with
      increasing BASIS-32 score, there was no association between change in GAF score
      and 1-year readmission. Although neither measure used alone demonstrated high
      predictive value, using both scores improved predictive ability over using
      clinician rating alone. In this setting, self-report was better than clinician
      rating in predicting psychiatric outcome. Differences between the two in relation
      to other outcomes need to be examined.

PMID- 16799833
TI  - Phenotyping of aggressive behavior in golden retriever dogs with a questionnaire.
AB  - Reliable and valid phenotyping is crucial for our study of genetic factors
      underlying aggression in Golden Retriever dogs. A mail questionnaire based on the
      Canine Behavioral Assessment and Research Questionnaire (CBARQ; Hsu and Serpell,
      2003, JAVMA 223(9):1293-1300) was used to assess behavioral phenotypes. Owners of
      228 Golden Retrievers completed the questionnaire. These dogs had been referred
      to our clinic for aggression problems several years earlier or they were related
      to aggressive dogs. In this paper, three sets of results are presented, which
      indicate that behavior scores from the CBARQ can be applied to genetic studies.
      First, factor analysis demonstrated that CBARQ items can be grouped into 10
      behavioral traits, including three types of aggression: stranger-directed
      aggression, owner-directed aggression, and dog-directed aggression. The results
      were remarkably similar to those reported by Hsu and Serpell. The aggression
      scores showed considerable variation in our dog families, which is a prerequisite
      for genetic studies. Second, retrospective questions enabled us to study changes
      in the aggressive behavior of the dogs in the course of time. After an average
      time interval of 4.3 years, over 50% of the dogs had become less aggressive.
      Third, we analyzed data obtained with an aggression test of 83 dogs. Two out of
      the three CBARQ aggression factors were also found in the aggression test data.

PMID- 16799835
TI  - "Any decision is better than none" decision-making about sex of rearing for
      siblings with 17beta-hydroxysteroid-dehydrogenase-3 deficiency.
AB  - Children with 17beta-hydroxysteroid-dehydrogenase-3 (17beta-HSD-3) deficiency
      have a defect of testosterone biosynthesis with subsequent diminished
      virilization in XY individuals. Some are raised as girls and some as boys. There
      were two purposes of this case report: First, it analyzed the process of decision
      making in a family with a pair of siblings with identical mutations leading to
      17beta-HSD-3 deficiency whose parents chose to raise one child as a boy and one
      as a girl. This analysis was based on narrative interviews with the parents.
      Second, we assessed the gender role behavior and gender identity in the children
      to examine if the psychosexual development of these children correspond with the
      sex of rearing their parents chose. When participating in the study, the children
      were 7 (boy) and 5 (girl) years old. Parents described a difficult process of
      decision-making and voiced concerns about lack of appropriate and understandable
      information, and anticipated decision regret. However, they did not feel that the
      decision to "normalize" the external genitalia should have been deferred. Both
      children appeared to show age-typical gender-related behavior and did not show
      any signs of physical or mental distress.

PMID- 16799834
TI  - Influence of the preimplantation embryo development (Ped) gene on embryonic
      platelet-activating factor (PAF) levels.
AB  - PURPOSE: A major gene responsible for the control of preimplantation cleavage
      rate is the Ped gene, the product of which is the Qa-2 protein. Fast, but not
      slow developing mouse embryos express the Qa-2 protein. Platelet-activating
      factor (PAF) is a novel and potent signaling phospholipid that has unique
      pleiotropic properties in addition to platelet activation. PAF plays a
      significant role in virtually every reproductive event, including ovulation,
      fertilization, implantation, and parturition. The role of the Ped gene in PAF
      production by preimplantation embryos is yet to be established. The presence of
      this gene provides embryos with a reproductive advantage over those that are Ped
      negative, and may also serve as a regulator of PAF synthesis. The study
      hypothesis is that the amount of PAF produced is dependent upon the presence or
      absence of the Ped gene. METHODS: B6.K1 (Ped negative) and B6.K2 (Ped positive)
      mouse embryo-conditioned culture media were assayed for PAF content by a PAF
      specific radioimmunoassay. RESULTS: There was a significant (p < 0.001)
      difference in blastocyst development rates between the Ped+ B6.K2 (61.0%) and the
      Ped- B6.K1 (25.3%) embryo culture groups. There was a significant difference (p <
      0.05) in PAF production between the Ped+ B6.K2 (4.70+/-0.46 pmol per embryo)
      embryo culture group and the Ped- B6.K1 (10.02+/-3.49 pmol per embryo) embryo
      group. The B6.K1 (Ped-) embryo group produced >2x more PAF than did the B6.K2
      (Ped+) group. CONCLUSIONS: The Ped gene plays a role in PAF production and
      release in preimplantation stage embryos. The use of two mouse identical strains,
      except for the Ped gene, show that its presence is associated with an increase in
      developmental potential. Embryos where the Ped gene was absent produced
      significantly higher levels of PAF, which may aid in their survival.

PMID- 16799836
TI  - Sociosexuality in women and preference for facial masculinization and somatotype
      in men.
AB  - Sociosexual orientation reflects individual differences in openness to short-term
      sexual relationships. We predicted that women with less restricted sociosexuality
      would be differentially attracted to highly masculinized male faces and bodies.
      In 2 studies, we investigated preference for male masculinization as a function
      of female sociosexuality. In Study 1, 40 female university students rated the
      attractiveness of pictures of male faces and somatotypes differing in
      masculinization level. All women preferred the faces with average levels of
      masculinity and the mesomorph somatotype; however, women with less restricted
      sociosexuality found the faces of men more attractive in general and showed
      relatively greater preference for masculinized bodies than did women with more
      restricted sociosexuality. In Study 2, 56 women met with 2 equally attractive
      male confederates, 1 highly masculinized and 1 less masculinized, in a "speed
      dating" scenario. After each date, women indicated their interest in each man for
      short-term and long-term relationships via questionnaire. In this more
      naturalistic context, sociosexuality was related to an increased interest for the
      more highly masculinized man in the context of short-term dating. Female
      sociosexuality appears to be related to preferences for higher levels of male
      masculinization.

PMID- 16799837
TI  - Condom use measurement in 56 studies of sexual risk behavior: review and
      recommendations.
AB  - Despite numerous studies that measure self-reported condom use, there is
      currently no agreed upon "gold standard" in terms of the best way to assess
      condom use. The purpose of the current study was to review measures of self
      reported condom use within correlational studies of sexual risk behavior, and to
      evaluate such measures on the basis of suggestions from the methodological
      literature. An additional purpose was to examine specifically whether measures
      published in the correlational literature have improved over time. A systematic
      review of studies was undertaken and specific review criteria were used to guide
      the inclusion of studies. A final set of 56 studies that contained 72 measures of
      self-reported condom use were included in the review. These measures were coded
      and evaluated on 12 dimensions, including measure type, number of response
      categories, recall period, sex partner specificity, and sex act specificity.
      Results indicated a great amount of diversity in terms of how condom use has been
      measured in the literature. Although results indicated that measures published
      between 1996 and 2003 were of higher quality on a number of dimensions as
      compared to 1989-1995, a number of these gains were minimal and in some cases
      measures have decreased in quality. The overall conclusion is that the sexual
      risk behavior literature should implement more of the recommendations made by
      methodological scholars in this area. Specific recommendations are summarized and
      presented in a way that may be helpful in guiding the development of future
      measures of self-reported condom use.

PMID- 16799838
TI  - Clinical and theoretical parallels between desire for limb amputation and gender
      identity disorder.
AB  - Desire for amputation of a healthy limb has usually been regarded as a paraphilia
      (apotemnophilia), but some researchers propose that it may be a disorder of
      identity, similar to Gender Identity Disorder (GID) or transsexualism.
      Similarities between the desire for limb amputation and nonhomosexual male-to
      female (MtF) transsexualism include profound dissatisfaction with embodiment,
      related paraphilias from which the conditions plausibly derive (apotemnophilia
      and autogynephilia), sexual arousal from simulation of the sought-after status
      (pretending to be an amputee and transvestism), attraction to persons with the
      same body type one wants to acquire, and an elevated prevalence of other
      paraphilic interests. K. Freund and R. Blanchard (1993) proposed that
      nonhomosexual MtF transsexualism represents an erotic target location error, in
      which men whose preferred erotic targets are women also eroticize their own
      feminized bodies. Desire for limb amputation may also reflect an erotic target
      location error, occurring in combination with an unusual erotic target preference
      for amputees. This model predicts that persons who desire limb amputation would
      almost always be attracted to amputees and would display an increased prevalence
      of gender identity problems, both of which have been observed. Persons who desire
      limb amputation and nonhomosexual MtF transsexuals often assert that their
      motives for wanting to change their bodies reflect issues of identity rather than
      sexuality, but because erotic/romantic orientations contribute significantly to
      identity, such distinctions may not be meaningful. Experience with nonhomosexual
      MtF transsexualism suggests possible directions for research and treatment for
      persons who desire limb amputation.

PMID- 16799839
TI  - Beyond sex offenses.

PMID- 16799840
TI  - Success is all in the measures: androgenousness, curvaceousness, and starring
      frequencies in adult media actresses.
AB  - The debate of whether body-mass index (BMI) or waist-to-hip ratio (WHR) is the
      primary visual cue to female physical attractiveness (FPA) has generated
      considerable interest. However, experiments addressing this question typically
      have limited ecological validity and do not capture the ultimate goal of FPA,
      which is to elicit male sexual arousal. Hence, using an unobtrusive measures
      design, we retrieved movie and magazine starring frequencies of 125 adult media
      actresses from a company's database, operationalized starring frequencies as FPA
      measures, and tested their relationship to actresses' anthropometric data. Low
      BMI was related to frequent movie starring, while WHR, waist-to-bust ratio (WBR),
      and bust size were not. Conversely, low WHR, low WBR, and larger bust size were
      related to frequent magazine starring, while BMI was not. Visual cues to FPA
      might be domain-specific, with androgenousness cues salient for attractiveness
      evaluation of moving bodies and curvaceousness cues salient for posing bodies.

PMID- 16799841
TI  - Suicidality and sexual orientation: differences between men and women in a
      general population-based sample from the Netherlands.
AB  - Homosexuality has been shown to be associated with suicidality and mental
      disorders. It is unclear whether homosexuality is related to suicidality,
      independently of mental disorders. This study assessed differences in lifetime
      symptoms of suicidality (death ideation, death wishes, suicide contemplation, and
      deliberate self-harm) between homosexual and heterosexual men and women,
      controlling for lifetime psychiatric morbidity. Interaction effects of age and
      the role of perceived discrimination were also examined. Data were collected on a
      representative sample of the Dutch population aged 18-64 years. Classification as
      heterosexual or homosexual was based upon reported sexual behavior in the
      preceding year. Of those sexually active, 2.8% of 2,878 men and 1.4% of 3,120
      women had had same-sex partners. Homosexual men differed from their heterosexual
      counterparts on all four suicide symptoms (OR ranging from 2.58 to 10.23, with
      higher ORs for more severe symptoms), and on the sum total of the four symptoms;
      homosexual women only differed from heterosexual women on suicide contemplation
      (OR=2.12). Controlling for psychiatric morbidity decreased the ORs, but among men
      all associations were still significant; the significance for suicide
      contemplation among women disappeared. Younger homosexuals were not at lower risk
      for suicidality than older homosexuals in comparison with their heterosexual
      counterparts. Among homosexual men, perceived discrimination was associated with
      suicidality. This study suggests that even in a country with a comparatively
      tolerant climate regarding homosexuality, homosexual men were at much higher risk
      for suicidality than heterosexual men. This relationship could not only be
      attributed to their higher psychiatric morbidity. In women, there was no such
      clear relationship.

PMID- 16799842
TI  - Sero-positive African Americans' beliefs about alcohol and their impact on anti
      retroviral adherence.
AB  - Alcohol consumption has been associated with HIV disease progression; yet, the
      nature of this association is poorly understood. This study sought to determine
      the influence of patient beliefs about alcohol on ART adherence, and elucidate
      clinician beliefs about drinking and taking ART. Most patients (85%) believed
      alcohol and ART do not mix. The three alcohol consumption groups, light,
      moderate, and heavy, differed in their beliefs about drinking and ART with 64% of
      light and 55% of moderate drinkers skipping ART when drinking compared to 29% of
      heavy drinkers. Beliefs were derived from folk models of alcohol-ART interaction.
      Patients 50 and older were less likely to skip ART when drinking. Alcohol appears
      to affect adherence through decisions to forgo ART when drinking not through
      drunken forgetfulness. Furthermore, over one-half of clinicians believed alcohol
      and ART should not be taken together. These findings have implications for
      patient care and physician training.

PMID- 16799843
TI  - Long-term female condom use among vulnerable populations in Brazil.
AB  - We carried out an evaluative study on factors associated with long-term use of
      female condoms for STI/HIV prevention. A total of 255 women and 29 men who were
      using female condoms for at least 4 months participated in
      qualitative/quantitative interviews. The study was conducted in six Brazilian
      cities. Four primary themes were identified as influencing acceptability and
      adoption of the female condom: (1) personal "assistance" (counseling) during the
      early adoption phase; (2) safety; (3) pleasure; and (4) increased sense of power
      for safer sex negotiation. Alternate use of male and female condoms was the norm
      among participants, but for approximately one third of the sample, the female
      condom was the preferred option for safer sex. The study findings suggest that
      providing clients with explicit and sustained intervention strategies may have a
      decisive influence on long-term adoption of female condoms.

PMID- 16799844
TI  - Time-course of semantic composition: the case of aspectual coercion.
AB  - We examine the time-course of semantic structure formation during real-time
      sentence comprehension. We do this through the lens of aspectual coercion, a
      semantic combinatorial operation that lacks morpho-syntactic reflections, yet is
      indispensable for sentence interpretation. We describe two experiments.
      Experiment 1 replicates the results of a previously published study (Pinango,
      Zurif, & Jackendoff, Journal of Psycholinguistic Research, 28(4), 395-414 1999)
      showing that the cost of implementing aspectual coercion is detectable as late as
      250 ms after the operation is licensed. Experiment 2 expands the window of
      observation by revealing that the implementation of aspectual coercion is not
      detectable immediately upon its being licensed, that is, at the point at which
      the syntactic representation is assumed to be fully formed. These findings
      suggest a dissociation in the integration of information, in which semantic
      composition--even mandatory and automatic semantic composition-takes time to
      develop after it is syntactically licensed to do so.

PMID- 16799845
TI  - A comparison of alternative strategies for cost-effective water quality
      management in lakes.
AB  - Roughly 45% of the assessed lakes in the United States are impaired for one or
      more reasons. Eutrophication due to excess phosphorus loading is common in many
      impaired lakes. Various strategies are available to lake residents for addressing
      declining lake water quality, including septic system upgrades and establishing
      riparian buffers. This study examines 25 lakes to determine whether septic
      upgrades or riparian buffers are a more cost-effective strategy to meet a
      phosphorus reduction target. We find that riparian buffers are the more cost
      effective strategy in every case but one. Large transaction costs associated with
      the negotiation and monitoring of riparian buffers, however, may be prohibiting
      lake residents from implementing the most cost-effective strategy.

PMID- 16799850
TI  - The importance of thrombophilia in the treatment of Paget-Schroetter syndrome.
AB  - Venous thoracic outlet syndrome (V-TOS) and associated subclavian vein thrombosis
      (SVT) result in significant patient morbidity and can be difficult to manage.
      Previous studies have suggested that both mechanical compressive factors and
      pathological alterations in patient coagulation may contribute to the development
      of SVT; however, no study has specifically evaluated the role of thrombophilia in
      the treatment of V-TOS and the need for long-term anticoagulation as an adjunct
      to surgical decompression. This retrospective study describes the clinical
      courses of 18 patients treated for V-TOS with and without acute SVT. In this
      review, 67% of patients with SVT are found to have relatively common coagulation
      disorders and 90% of postoperative complications were associated with some form
      of thrombophilia. This study suggests that thrombophilia may play an important
      role in the pathogenesis of V-TOS and may be a determinant of the success of
      surgical decompression. Clotting disorders should therefore be aggressively
      evaluated in this patient population and can improve therapeutic outcome.

PMID- 16799851
TI  - Type 2 endoleaks after abdominal aortic aneurysm stent grafting with systematic
      mesenteric and lumbar coil embolization.
AB  - We evaluated the results of our policy of systematic coil embolization of the
      inferior mesenteric artery (IMA) and/or lumbar arteries (LAs) prior to
      endovascular abdominal aortic aneurysm (AAA) repair (EVAR). We retrospectively
      reviewed all patients undergoing EVAR over a 4-year period at one hospital.
      Results were analyzed using uni- and multivariate analyses. Fifty-five male
      patients with an average age of 71 years were evaluated. Follow-up averaged 15 +/
      13 months. The IMA was either coiled or occluded in 30 cases. One or more LAs
      were coiled in 29 patients. An average of 1.3 LAs per patients were coiled (range
      0-6). There were no immediate or late complications from coiling. At last follow
      up, 14 AAAs showed no change in diameter, one increased by 2 mm, and the
      remainder (n = 40) decreased by 7.5 +/- 6 mm in maximal diameter. Only five (9%)
      type 2 endoleaks were detected during follow-up. Three were associated with AAA
      size increase. Four of the five were treated with additional coiling, with good
      results. By logistic regression, neither endoleak occurrence nor AAA shrinkage
      correlated with LA or IMA coiling. However, by multivariate analysis,
      completeness of lumbar coiling correlated negatively with aneurysm shrinkage (p =
      0.04) and IMA coiling correlated positively with aneurysm shrinkage (p = 0.04).
      Coil embolization of the IMA and/or LAs prior to EVAR can be safely accomplished
      in a large number of cases and is associated with a low incidence of type 2
      endoleaks. We cannot at present demonstrate a benefit to LA embolization in terms
      of endoleak prevention or AAA shrinkage. However, IMA embolization may be of
      benefit in terms of AAA shrinkage.

PMID- 16799852
TI  - Carotid endarterectomy with bovine pericardium patch angioplasty: mid-term
      results.
AB  - The objective of this study was to assess the efficacy of bovine pericardium (BP)
      as a patch material in carotid endarterectomy (CEA) in terms of peri- and
      postoperative complications and the incidence of recurrent stenosis. During a 4
      year period, 148 CEAs were performed in 138 consecutive patients. The study group
      included elective, emergency, and combined with cardiac operation CEAs in both
      symptomatic and asymptomatic carotid artery disease patients. Patch angioplasty
      using the BP followed the standard CEA in all patients. Postoperative follow-up
      included clinical examination and periodical color duplex scans at 3, 6, and 12
      months and yearly thereafter. Surgical outcome was evaluated by the operation
      related parameters, early and late mortality and morbidity rates, and the
      incidence of recurrent stenosis. All CEAs were performed without any unfavorable
      event. In the early postoperative period, there were no deaths and the morbidity
      consisted of transient cranial nerve paresis (4.7%) in seven patients and two
      ipsilateral strokes (1.4%). During the follow-up period, three patients (2%)
      developed significant carotid restenosis, though they remain asymptomatic, while
      there were no deaths related to the CEA. Patch angioplasty of the carotid artery
      using BP showed unwittingly early and mid-term surgical outcome. Our results
      demonstrate the BP to be a suitable patch material for routine use in carotid
      surgery.

PMID- 16799853
TI  - Upper extremity vascular injury: a current in-theater wartime report from
      Operation Iraqi Freedom.
AB  - Past wartime experience and recent civilian reports indicate upper extremity (UE)
      vascular injury occurs less often and with less limb loss than lower extremity
      (LE) injury. Given advances in critical care, damage control techniques, and
      military armor technology, the objective of this evaluation was to define
      contemporary patterns of UE injury and effectiveness of vascular surgical
      management in UE vascular injury during Operation Iraqi Freedom (OIF). From 1
      September 2004 through 31 August 2005, 2,473 combat-related injuries were treated
      at the central echelon III surgical facility in Iraq. Patients with UE vascular
      injuries upon arrival were reviewed. Vessels injured were delineated. Therapeutic
      interventions, early limb viability, and complication rates following vascular
      repair were recorded. Of casualties treated during the study period, 43 (1.7%) UE
      and 83 (3.3%) LE vascular injuries were identified. Of the UE injuries, 11 (26%)
      had been operated on at forward locations and six (14%) had temporary shunts in
      place upon arrival at our facility. Injury levels included 10 (23%) subclavian
      axillary, 25 (58%) brachial, and 10 (23%) distal to the brachial bifurcation. Two
      patients had multilevel injury. Twenty-eight grafts were placed, and 10 vessel
      repairs and eight ligations were performed. Two (4.7%) brachial interposition
      grafts required removal due to infection. Four (9.3%) subacute brachial graft
      thromboses occurred. Four (9.3%) patients underwent early UE amputation. In this
      most recent U.S. military evaluation of wartime UE vascular injury, UE injury
      appears rare, with LE injury twice as frequent. Yet, UE limb loss appears more
      substantial than noted previously. These findings are likely related to
      significant tissue destruction occurring with the combined mechanisms of injury
      sustained in OIF.

PMID- 16799858
TI  - Overt rectal prolapse following repair of stage IV vaginal vault prolapse.
AB  - Pelvic organ prolapse is an increasingly common problem as women are living
      longer. With the growing numbers of surgeries performed to correct this problem,
      further research is needed to understand the long-term success as well as
      possible complications of these procedures. One potential complication that needs
      further study is de novo rectal prolapse after repair of pelvic organ prolapse,
      specifically after colpocleisis. Defacography may be an important part of the
      preoperative workup in the patient with pelvic organ prolapse. Currently, there
      is a controversy as to whether internal, or occult, rectal prolapse on
      defacography should be repaired at the time of other pelvic reconstructive
      surgery. We report on a case of overt rectal prolapse after repair of Stage IV
      vaginal vault prolapse with a colpocleisis, levator ani plication, and a
      minimally invasive midurethral sling. We discuss the issues surrounding
      preoperative management of these patients and propose a theory explaining why
      prolapse in other areas of the pelvis may occur after reconstructive surgery.

PMID- 16799859
TI  - Probabilistic approach to determining unbiased random-coil carbon-13 chemical
      shift values from the protein chemical shift database.
AB  - We describe a probabilistic model for deriving, from the database of assigned
      chemical shifts, a set of random coil chemical shift values that are "unbiased"
      insofar as contributions from detectable secondary structure have been minimized
      (RCCSu). We have used this approach to derive a set of RCCSu values for 13Calpha
      and 13Cbeta for 17 of the 20 standard amino acid residue types by taking
      advantage of the known opposite conformational dependence of these parameters. We
      present a second probabilistic approach that utilizes the maximum entropy
      principle to analyze the database of 13Calpha and 13Cbeta chemical shifts
      considered separately; this approach yielded a second set of random coil chemical
      shifts (RCCSmax-ent). Both new approaches analyze the chemical shift database
      without reference to known structure. Prior approaches have used either the
      chemical shifts of small peptides assumed to model the random coil state
      (RCCSpeptide) or statistical analysis of chemical shifts associated with
      structure not in helical or strand conformation (RCCSstruct-stat). We show that
      the RCCSmax-ent values are strikingly similar to published RCCSpeptide and
      RCCSstruct-stat values. By contrast, the RCCSu values differ significantly from
      both published types of random coil chemical shift values. The differences
      (RCCSpeptide - RCCSu) for individual residue types show a correlation with known
      intrinsic conformational propensities. These results suggest that random coil
      chemical shift values from both prior approaches are biased by conformational
      preferences. RCCSu values appear to be consistent with the current concept of the
      "random coil" as the state in which the geometry of the polypeptide ensemble
      samples the allowed region of (phi, psi)-space in the absence of any dominant
      stabilizing interactions and thus represent an improved basis for the detection
      of secondary structure. Coupled with the growing database of chemical shifts,
      this probabilistic approach makes it possible to refine relationships among
      chemical shifts, their conformational propensities, and their dependence on pH,
      temperature, or neighboring residue type.

PMID- 16799860
TI  - NMR assignment of the protein nsp3a from SARS-CoV.

PMID- 16799861
TI  - Comparative effects of direct cadmium contamination on gene expression in gills,
      liver, skeletal muscles and brain of the zebrafish (Danio rerio).
AB  - The effects of cadmium (Cd) on gene expression were examined in four organs
      (gills, liver, skeletal muscles and brain) of the zebrafish. Adult male fish were
      subjected to three different water contamination pressures over periods of 7 and
      21 days: control medium (C(0): no Cd added) and two contaminated media (C(1): 1.9
      +/- 0.6 microg Cd l(-1), and C(2): 9.6 +/- 2.9 microg Cd l(-1)). Fourteen genes
      involved in antioxidant defences, metal chelation, active efflux of organic
      compounds, mitochondrial metabolism, DNA repair and apoptosis were selected and
      their expression levels investigated by quantitative real-time PCR. Cadmium
      concentrations were determined in the four organs and metallothionein (MT)
      protein levels investigated in brain, liver and gills. Although skeletal muscle
      was a poor Cd-accumulating tissue, many genes were up-regulated at day 7: mt1,
      cyt, bax, gadd and rad51 genes. Three additional genes, c-jun, pyc and tap, were
      up-regulated in muscles at day 21 whereas bax, gadd and rad51 had returned to
      basal levels. Surprisingly, mt1 and c-jun were the only genes displaying a
      differential induction after 21 days in liver, although this organ accumulated
      the highest cadmium concentration. In brain, only mt1, mt2 and c-jun genes were
      up-regulated after 21 days. In gills, the highest response was observed after 7
      days, featuring the differential expression of oxidative stress-response hsp70
      and mitochondrial sod genes, along with genes involved in mitochondrial
      metabolism and metal detoxification. Then, after 21 days, the expression of
      almost every genes returned to basal levels while both mt1 and mt2 genes were up
      regulated.

PMID- 16799862
TI  - Cytochrome c oxydase subunit I gene is up-regulated by cadmium in freshwater and
      marine bivalves.
AB  - Inhibition of the mitochondrial electron transfer chain and induction of reactive
      oxygen species (ROS) production are one of the roots of cadmium (Cd) toxicity. To
      appreciate the impact of Cd on mitochondria, we focused on the expression of CoxI
      gene which encodes the subunit I of the Cytochrome c oxidase (complex IV of the
      respiratory chain). CoxI gene expression was studied by real-time quantitative
      PCR in three species: two freshwater bivalves (Corbicula fluminea and Dreissena
      polymorpha) and one marine bivalve (diploid or triploid Crassostrea gigas).
      Bivalves were exposed for 10 or 14 days to 0.13 microM Cd(2+) and 15.3 microM
      Zn(2+) in controlled laboratory conditions. We demonstrate that in the three
      mollusk species CoxI gene was up-regulated by Cd. Zinc (Zn), which is known to
      have antioxidant properties, had no effect on CoxI gene expression. In the
      presence of Cd and Zn, CoxI gene inducibility was lower than after a single Cd
      exposure, in each species; result that could not be fully explained by a
      decreased Cd accumulation. CoxI gene induction by Cd was 4.8-fold higher in
      triploid oysters than in diploid ones, indicating a possible influence of
      triploidy on animal responses to Cd contamination.

PMID- 16799863
TI  - Prooxidant action of maltol: role of transition metals in the generation of
      reactive oxygen species and enhanced formation of 8-hydroxy-2'-deoxyguanosine
      formation in DNA.
AB  - Maltol (3-hydroxy-2-methyl-4-pyrone) produced reactive oxygen species as a
      complex with transition metals. Maltol/iron complex inactivated aconitase the
      most sensitive enzyme to oxidative stress. The inactivation of aconitase was iron
      dependent, and prevented by TEMPOL, a scavenger of reactive oxygen species,
      suggesting that the maltol/iron-mediated generation of superoxide anion is
      responsible for the inactivation of aconitase. Addition of maltol effectively
      enhanced the ascorbate/copper-mediated formation of 8-hydroxy-2'-deoxyguanosine
      in DNA. Oxidation of ascorbic acid by CuSO(4) was effectively stimulated by
      addition of maltol, and the enhanced oxidation rate was markedly inhibited by the
      addition of catalase and superoxide dismutase. These results suggest that maltol
      can stimulate the copper reduction coupled with the oxidation of ascorbate,
      resulting in the production of superoxide radical which in turn converts to
      hydrogen peroxide and hydroxyl radical. Cytotoxic effect of maltol can be
      explained by its prooxidant properties: maltol/transition metal complex generates
      reactive oxygen species causing the inactivation of aconitase and the production
      of hydroxyl radical causing the formation of DNA base adduct.

PMID- 16799864
TI  - Interaction of FurA from Anabaena sp. PCC 7120 with DNA: a reducing environment
      and the presence of Mn(2+) are positive effectors in the binding to isiB and furA
      promoters.
AB  - The Fur (ferric uptake regulator) protein is a global regulator in most
      prokaryotes that controls a large number of genes. Fur is a classical repressor
      that uses ferrous iron as co-repressor and binds to specific DNA sequences (iron
      boxes) as a dimer. Three different genes coding for Fur homologues have been
      identified in Anabaena sp. PCC 7120. FurA controls the transcription of
      flavodoxin, the product of the isiB gene, and is moderately autoregulated. In
      this work, the promoter of the furA gene was defined and the FurA protected
      regions in the furA and isiB promoters were identified, showing that the binding
      sites for Anabaena FurA contain A/T-rich sequences with a variable arrangement
      compared to the conventional 19-base pair Fur consensus. The influence of
      different factors on the interaction between FurA and the promoters was evaluated
      in vitro. The affinity of FurA for the DNA targets was significantly affected by
      the redox status of this regulator and the presence of Mn(2+). The optimal
      binding conditions were observed in the presence of both Mn(2+) and DTT. Those
      results suggest that, in addition to iron availability, FurA-DNA interaction is
      modulated by redox conditions.

PMID- 16799865
TI  - Quantification of hydroxamate siderophores in soil solutions of podzolic soil
      profiles in Sweden.
AB  - Concentrations up to 2 and 12 nM of the hydroxamate siderophores ferrichrome and
      ferricrocin, respectively, were identified in soil solutions of podzolic forest
      soils at four sites in both northern and southern Sweden. No ferrichrysin was
      detected. As with the dissolved organic carbon and low molecular mass organic
      acids, the highest concentrations of the siderophores were found in the upper
      layers i.e. the mor layer, the eluvial and upper illuvial horizons. At the
      southern sites, the concentrations of ferrichrome and ferricrocin were both of
      similar magnitude and did not differ between the two sites. In contrast, soil
      solutions at the two northern sites contained more ferricrocin than ferrichrome;
      the ferricrocin concentrations were also higher at the northern sites than at the
      southern sites. Analyses were performed by high performance liquid chromatography
      with a porous graphitic carbon column on which ferrichrome, ferricrocin and
      ferrichrysin were separated. Detection by electrospray ionization mass
      spectrometry (ESI-MS) combined with on-line sample pre-concentration, by means of
      column-switching, enabled detection limits of 0.1-0.2 nM for ferrichrome,
      ferrichrysin and ferricrocin. The structural identities of the siderophores were
      further verified by MS/MS fragmentation. Fragmentation of ferrichrome,
      ferricrocin and ferrichrysin occurred mainly via peptide cleavage. The most
      intense fragments were typified by the loss of one of the three iron(III)
      chelating hydroxamate residues, i.e N(5)-acyl-N(5)-hydroxy ornithine.

PMID- 16799866
TI  - The influence of long-term mercury exposure on selenium availability in tissues:
      an evaluation of data.
AB  - The precise mechanisms of mercury accumulation and retention are still unclear.
      Generally, the association of mercury with selenium is used to explain these
      phenomena. It seems that the presence of coaccumulated endogenous Se can protect
      cells from the harmful effects of Hg. However, as speculated by some authors,
      this binding of Se to Hg can also result in a relative deficiency of biologically
      available Se needed for selenoenzyme syntheses. Deriving from the assumption that
      Hg deposited in tissues is bound to Se in a 1:1 ratio, the quantity of non-Hg
      bound Se could be calculated by the difference between the molar contents of the
      two elements (Se(mol)-Hg(mol)). In this study we applied such an approach to the
      data from our previous investigation, where Hg and Se concentrations were
      determined in autopsy samples of mercury exposed retired Idrija mercury mine
      workers, Idrija residents living in a Hg contaminated environment and a control
      group with no known Hg exposure from the environment. Based on these data we
      tried to estimate the influence of Hg exposure on the physiologically available
      selenium content in selected tissues, particularly endocrine glands and brain
      tissues. Comparing the calculated values of (Se(mol)- Hg(mol)) it was found that
      for Idrija residents the values were similar to those of the control group and as
      expected, diminished values were found in some mercury-loaded organs of retired
      Idrija miners. It could be speculated that in Idrija residents Hg sequestration
      of selenium is sufficiently compensated by increased Se levels, but that
      particularly in active miners and in some organs of retired miners, the activity
      and/or synthesis of selenoenzymes could be disturbed.

PMID- 16799867
TI  - Stingless bee antennae: a magnetic sensory organ?
AB  - Magnetic material in the body parts of the stingless bee Schwarziana
      quadripunctata, heads, pairs of antennae, thorax and abdomens, were investigated
      by SQUID magnetometry and Ferromagnetic Resonance (FMR). The saturation, J(s) and
      remanent, J(r), magnetizations and coercive field H(c) are determined from the
      hysteresis curves. From H(c) and J(r)/J(s) the magnetic particle sizes are
      estimated. The J(s) and the FMR spectral absorption areas yield 23+/-3%, 45+/-5%,
      15+/-2% and 19+/-4% magnetic material contributions of head, pair of antennae,
      thorax and abdomen, respectively, similar to those observed in the migratory ant
      Pachycondyla marginata. This result is discussed in light of the hypothesis of
      antennae as a magnetosensor structure.

PMID- 16799868
TI  - Zinc protects rat liver histo-architecture from detrimental effects of nickel.
AB  - This study was designed to examine the protective potential of zinc on the
      histoarchitecture distortion induced by nickel in rats. Male Sprauge Dawley (S.D)
      rats received either nickel alone in the form NiSO(4) x 6H(2)O at a dose of 800
      mg/l in drinking water, zinc alone in the form of ZnSO(4) x 7H(2)O at a dose of
      227 mg/l in drinking water, or nickel plus zinc or drinking water alone for a
      total duration of eight weeks. The effects of different treatments were studied
      on rat liver histoarchitecture by using both light and transmission electron
      microscopes. Normal control and zinc treated animals revealed normal histology of
      liver, however, nickel treated animals resulted in drastic alterations of normal
      hepatic histoarchitecture, after 8 weeks of treatment. Administration of zinc to
      nickel treated rats resulted in marked improvement in the structure of
      hepatocytes, thus emphasizing the protective potential of zinc in restoring the
      altered hepatic histoarchitecture close to the histoarchitecture of normal
      animals.

PMID- 16799869
TI  - Purification and characterization of canine serum ferritin-binding proteins.
AB  - Ferritin-binding protein (FBP) is known to interact with circulating ferritins in
      mammals. Canine FBPs were purified from canine serum by affinity chromatography
      and were identified as IgM, IgG, and IgA by immunoblotting with alkaline
      phosphatase-labeled antibodies to canine IgM, IgG, and IgA heavy chains.
      Following further purification by application to a Sephacryl S-300 column, canine
      FBPs were separated into 81.3- and 27.7-kDa bands by sodium dodecyl sulfate
      polyacryamide gel electrophoresis, and the 81.3-kDa band reacted with the anti
      canine IgM heavy chain antibody. Purified canine FBP bound to canine liver
      ferritin, but not to canine albumin and transferrin. FBP showed greater binding
      to the expressed bovine ferritin H-chain homopolymer than to the expressed bovine
      ferritin L-chain homopolymer. The binding of FBP with canine liver ferritin was
      dose-dependently inhibited by anti-rat liver ferritin antibody, and the anti
      ferritin antibody dissociated the bound FBP in a dose-dependent manner, even
      after binding FBP with liver ferritin. The canine ferritin H subunit peptide
      fragment with amino acid residues 148-155 (NH(2)-GDHVTNLR-COOH) in its C-terminal
      region was recognized by FBP. These results indicate that canine serum FBPs are
      autoantibodies to ferritin (IgM, IgG, and IgA) and that anti-ferritin
      autoantibody (IgM) recognizes the C-terminal region of ferritin H subunit.

PMID- 16799870
TI  - Ascorbate-mediated iron release from ferritin in the presence of alloxan.
AB  - Release of iron from ferritin requires reduction of ferric to ferrous iron. The
      iron can participate in the diabetogenic action of alloxan. We investigated the
      ability of ascorbate to catalyze the release of iron from ferritin in the
      presence of alloxan. Incubation of ferritin with ascorbate alone elicited iron
      release (33 nmol/10 min) and the generation of ascorbate free radical, suggesting
      a direct role for ascorbate in iron reduction. Iron release by ascorbate
      significantly increased in the presence of alloxan, but alloxan alone was unable
      to release measurable amounts of iron from ferritin. Superoxide dismutase
      significantly inhibited ascorbate-mediated iron release in the presence of
      alloxan, whereas catalase did not. The amount of alloxan radical (A.(-))
      generated in reaction systems containing both ascorbate and alloxan decreased
      significantly upon addition of ferritin, suggesting that A.(-) is directly
      involved in iron reduction. Although release of iron from ferritin and generation
      of A.(-) were also observed in reactions containing GSH and alloxan, the amount
      of iron released in these reactions was not totally dependent on the amount of
      A.(-) present, suggesting that other reductants in addition to A.(-) (such as
      dialuric acid) may be involved in iron release mediated by GSH and alloxan. These
      results suggest that A.(-) is the main reductant involved in ascorbate-mediated
      iron release from ferritin in the presence of alloxan and that both dialuric acid
      and A.(-) contribute to GSH/alloxan-mediated iron release.

PMID- 16799871
TI  - Basidiochrome -- a novel siderophore of the Orchidaceous Mycorrhizal Fungi
      Ceratobasidium and Rhizoctonia spp.
AB  - A novel trishydroxamate siderophore, named basidiochrome, was isolated as the
      principal siderophore from low-iron culture filtrates of Ceratobasidium and
      Rhizoctonia species which are known as mycorrhizal fungi associated with orchid
      roots. Ion-exchange chromatography and preparative HPLC yielded a pure compound
      which contained two components according to GC-MS analysis: L: -N(5)-hydroxy
      ornithine and 3-methyl-2-cis-pentenedioic acid (3-methyl-cis-glutaconic acid).
      FTICR-ESI-MS of both the iron-free and ferric form indicated an elemental
      composition of C(33)H(47)N(6)O(16)Fe (MW = 839) for the ferric form of
      basidiochrome. The connectivity was further elucidated by 2D-NMR techniques
      (HSQC, HMBC, COSY, NOESY) indicating that basidiochrome is a novel linear
      tripeptide consisting of three L: -N(5)-hydroxy-ornithines each linked to 3
      methyl-2-cis-pentenedioic acid residues.

PMID- 16799872
TI  - Abstracts of the 1st Annual Meeting of the Society of Cardiovascular Computed
      Tomography. July 13-16, 2006. Arlington, Virginia, USA.

PMID- 16799873
TI  - Cyclin A1 is a p53-induced gene that mediates apoptosis, G2/M arrest, and mitotic
      catastrophe in renal, ovarian, and lung carcinoma cells.
AB  - We were the first to identify cyclin A1 as a p53-induced gene by cDNA expression
      profiling of p53-sensitive and -resistant tumor cells [Maxwell S. A. and Davis G.
      E. (2000) Proc. Natl. Acad. Sci. USA 97, 13009-13014]. We show here that cyclin
      A1 can induce G2 cell cycle arrest, polyploidy, apoptosis, and mitotic
      catastrophe in H1299 non-small cell lung, TOV-21G ovarian, or 786-0 renal
      carcinoma cells. More cdk1 protein and kinase activities were observed in cyclin
      A1-induced cells than in GFP control-induced cells. Thus, cyclin A1 might mediate
      apoptosis and mitotic catastrophe through an unscheduled or inappropriate
      activation of cdk1. Two primary renal cell carcinomas expressing mutated p53
      exhibited reduced or absent expression of cyclin A1 relative to the corresponding
      normal tissue. Moreover, renal carcinoma-derived mutant p53s were deficient in
      inducing cyclin A1 expression in p53-null cells. Cyclin A1 but not cyclin A2 was
      upregulated in etoposide-treated tumor cells undergoing p53-dependent apoptosis
      and mitotic catastrophe. Forced upregulation of cyclin A2 did not induce
      apoptosis. The data implicate cyclin A1 as a downstream player in p53-dependent
      apoptosis and G2 arrest.

PMID- 16799874
TI  - Analysis of travelling waves associated with the modelling of aerosolised skin
      grafts.
AB  - A previous model developed by the authors investigates the growth patterns of
      keratinocyte cell colonies after they have been applied to a burn site using a
      spray technique. In this paper, we investigate a simplified one-dimensional
      version of the model. This model yields travelling wave solutions and we analyse
      the behaviour of the travelling waves. Approximations for the rate of healing and
      maximum values for both the active healing and the healed cell densities are
      obtained.

PMID- 16799875
TI  - Fast, reversible interaction of prion protein with RNA aptamers containing
      specific sequence patterns.
AB  - One of the unsolved problems in prion diseases relates to the physiological
      function of cellular prion protein (PrP), of which a misfolded isoform is the
      major component of the transmissible spongiform encephalopathies agent. Knowledge
      of the PrP-binding molecules may help in elucidating its role and understanding
      the pathological events underlying prion diseases. Because nucleic acids are
      known to bind PrP, we attempted to identify the preferred RNA sequences that bind
      to the ovine recombinant PrP. An in vitro selection approach (SELEX) was applied
      to a pool of 80-nucleotide(nt)-long RNAs containing a randomised 40-nt central
      region. The most frequently isolated aptamer, RM312, was also the best ligand (20
      nM KD value), according to both surface plasmon resonance and filter binding
      assays. The fast rates of association and dissociation of RM312 with immobilized
      PrP, which are reminiscent of biologically relevant interactions, could point to
      a physiological function of PrP towards cellular nucleic acids. The minimal
      sequence that we found necessary for binding of RM312 to PrP presents a striking
      similarity with one previously described PrP aptamer of comparable affinity. In
      addition, we here identify the two lysine clusters contained in the N-terminal
      part of PrP as its main nucleic-acid binding sites.

PMID- 16799876
TI  - Complex tracheal stenosis related to pulmonary artery sling and VACTER
      association.

PMID- 16799877
TI  - First in-human randomized comparison of an anodized niobium stent versus a
      standard stainless steel stent--an intravascular ultrasound and angiographic two
      center study: the VELA study.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that a niobium
      stent might lower the restenosis rate in de novo coronary lesions as compared to
      a bare metal stent. BACKGROUND: Recent data have suggested that inflammatory and
      allergic reactions to certain compounds in metal stents may play a role in the
      onset of restenosis. Thus, niobium as an inert material might be beneficial in
      lowering the rate of restenosis. METHODS: In this single blind, two-center
      prospective trial patients were randomized into two groups; the first group
      (n=32) received a niobium stent (VELA STF), the second group (n=33) a bare metal
      stent (Antares STF). Clinical follow-up was performed at 1 and 6 months,
      angiographic and intravascular ultrasound analyses were performed at the 6-month
      follow-up. RESULTS: All stents were successfully deployed. There was one stent
      thrombosis in each group. There were no significant differences concerning
      minimal lumen diameter, percent stenosis, and late lumen loss as assessed by
      intravascular ultrasound (IVUS) at the 6- month follow-up. At 30 days and at 6
      months, there were no differences observed between the two groups regarding the
      rate of major cardiac adverse events. Immediately after stent implantation
      minimal lumen diameter was significantly larger (p=0.01) and residual percent
      stenosis significantly lower (p=0.01) in the niobium stent group. CONCLUSION: The
      use of a niobium stent showed comparable results with other non-drug-eluting
      stents; however the inert qualities of this first generation niobium stent did
      not translate into a mid- or long-term benefit.

PMID- 16799878
TI  - Long-term follow-up of a malpositioned ventricular pacing lead via the aortic
      valve.

PMID- 16799879
TI  - Inadequate medical treatment of patients with coronary artery disease by primary
      care physicians in Germany.
AB  - AIMS: The DETECT study was performed to obtain representative data about the
      frequency, distribution, and treatment of patients with coronary artery disease
      (CAD) in the primary care setting in Germany. METHODS AND RESULTS: The DETECT
      study was a cross-sectional clinical- epidemiological survey of a nationally
      representative sample of 3795 primary care offices and 55,518 patients. Overall,
      12.4% of patients were diagnosed with CAD. Stable angina pectoris and myocardial
      infarction were the most frequent (4.2%) subgroups, followed by status post (s/p)
      percutaneous coronary interventions (PCI, 3.0%) and s/p coronary bypass surgery
      (2.2%). Patients with CAD were prescribed AT1 receptor antagonists (in 19.4% of
      cases), beta blockers (57.2%), ACE inhibitors (49.9%), antiplatelet agents
      (52.7%), statins (43.0%), and long-term nitrates (24.5%). When comparing all CAD
      patients with social health care insurance to those who had private insurance,
      private patients had significantly higher rates of revascularisation procedures
      and use of preventive medications. CONCLUSION: Great potential remains for
      improving secondary prevention in primary care in Germany to reduce the risk of
      further coronary or vascular events, especially in patients with social health
      care insurance.

PMID- 16799880
TI  - DNA methylation as a marker for the past and future.
AB  - Aberrant methylation of CpG islands in promoter regions can permanently
      inactivate tumor-suppressor genes, as mutations and chromosomal abnormalities do.
      In gastric cancers, CDKN2A, CDH1, and MLH1 are inactivated more frequently by
      aberrant methylation than by mutations, and novel tumor-suppressor genes
      inactivated by promoter methylation are being identified. We recently found that
      Helicobacter pylori (HP), a potent gastric carcinogen, induces aberrant
      methylation in gastric mucosae. When a panel of CpG islands was examined, some
      CpG islands were consistently methylated in gastric mucosae of individuals with
      HP infection, while others were resistant. The amount of methylated DNA molecules
      in the gastric mucosae (methylation level) fluctuated while active HP infection
      was present, but decreased after it was no longer present. Among individuals
      without active HP infection, methylation levels in the gastric mucosae were
      higher in individuals with gastric cancers than in those without. DNA methylation
      is emerging as a promising marker for past exposure to carcinogens and future
      risk of cancers.

PMID- 16799881
TI  - Acupuncture for functional gastrointestinal disorders.
AB  - Functional gastrointestinal (GI) symptoms are common in the general population.
      Especially, motor dysfunction of the GI tract and visceral hypersensitivity are
      important. Acupuncture has been used to treat GI symptoms in China for thousands
      of years. It is conceivable that acupuncture may be effective in patients with
      functional GI disorders because it has been shown to alter acid secretion, GI
      motility, and visceral pain. Acupuncture at the lower limbs (ST-36) causes muscle
      contractions via the somatoparasympathetic pathway, while at the upper abdomen
      (CV-12) it causes muscle relaxation via the somatosympathetic pathway. In some
      patients with gastroesophageal reflux disease (GERD) and functional dyspepsia
      (FD), peristalsis and gastric motility are impaired. The stimulatory effects of
      acupuncture at ST-36 on GI motility may be beneficial to patients with GERD or
      FD, as well as to those with constipation-predominant irritable bowel syndrome
      (IBS), who show delayed colonic transit. In contrast, the inhibitory effects of
      acupuncture at CV-12 on GI motility may be beneficial to patients with diarrhea
      predominant IBS, because enhanced colonic motility and accelerated colonic
      transit are reported in such patients. Acupuncture at CV-12 may inhibit gastric
      acid secretion via the somatosympathetic pathway. Thus, acupuncture may be
      beneficial to GERD patients. The antiemetic effects of acupuncture at PC-6
      (wrist) may be beneficial to patients with FD, whereas the antinociceptive
      effects of acupuncture at PC-6 and ST-36 may be beneficial to patients with
      visceral hypersensitivity. In the future, it is expected that acupuncture will be
      used in the treatment of patients with functional GI disorders.

PMID- 16799882
TI  - Dietary habits and stomach cancer in Mizoram, India.
AB  - BACKGROUND: An extremely high prevalence of stomach cancer was observed in
      Mizoram (India), where the population consumes uncommon food. The relation of
      food habits and stomach cancer was examined in this study. METHODS: A hospital
      based case-control study was conducted during 2001-2004 to determine the risk
      factors among 329 patients with histologically confirmed stomach cancer and 658
      matched controls. Food habits were determined by personal interview. RESULTS: An
      elevated risk of stomach cancer was observed with frequent consumption of sa-um
      [odds ratio (OR) 3.4] (sa-um is fermented pork fat, a traditional food) and with
      frequent consumption of smoked dried salted meat (OR 2.8) and fish (OR 2.5). Soda
      (alkali), used as a food additive, increased the risk of stomach cancer (OR 2.9).
      Helicobacter pylori infection was not found to be an independent risk factor for
      carcinogenesis of stomach cancer in this study. However, when H. pylori infection
      interacted with consumption of sa-um or smoked dried meat, it showed a
      significant association. CONCLUSION: Peculiar food habits in Mizoram might be
      associated with the high prevalence of stomach cancer in Mizoram along with other
      factors. H. pylori infection might increase the risk of stomach cancer, or it may
      play a role as a promoter of stomach cancer in Mizoram.

PMID- 16799883
TI  - Late toxicity in complete response cases after definitive chemoradiotherapy for
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: We retrospectively investigated long-term toxicity after concurrent
      chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma
      (ESCC). METHODS: Concurrent chemoradiotherapy was performed in 110 patients with
      T1 to T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted
      of protracted infusion of 5-fluorouracil 400 mg/m(2) per 24 h on days 1 to 5 and
      8 to 12, combined with 2-h infusion of cisplatin 40 mg/m(2) on days 1 and 8.
      Radiation treatment of the mediastinum at a dose of 30 Gy in 15 fractions was
      administered concomitantly with chemotherapy. A course schedule with a 3-week
      treatment and a 2-week break was applied twice, with a total radiation dose of 60
      Gy. For the assessment of toxicity, the Radiation Therapy Oncology Group/European
      Organization for Research and Treatment of Cancer late radiation morbidity
      scoring schema was adopted. RESULTS: A total of 81 patients were recruited in
      patients with stage I to IVA. Of 34 patients with complete response, 1 patient
      died as a result of acute myocardial infarction. Grade 2, 3, and 4 late
      toxicities occurred with the following incidences: pericarditis in 3 patients, 1
      patient, and 2 patients, respectively; heart failure in 0, 0, and 3 patients;
      pleural effusion in 2, 3, and 0 patients; and radiation pneumonitis in 0, 0, and
      1 patient, respectively. CONCLUSIONS: Definitive chemoradiotherapy for ESCC is
      effective with substantial toxicities. Further investigation is warranted to
      minimize the normal tissue toxicities.

PMID- 16799885
TI  - Will symptomatic gastroesophageal reflux disease develop into reflux esophagitis?
AB  - BACKGROUND: The objective of this study was to ascertain whether symptomatic
      gastroesophageal reflux disease (SGERD) without endoscopic evidence of
      inflammatory findings would develop into esophagitis. METHODS: Observation by
      endoscopic examination was conducted annually for 5 years, using as subjects 497
      patients among those who underwent gastroesophageal endoscopy in their health
      examination, but patients with findings of esophagitis and those who had
      undergone Helicobacter pylori eradication therapy were excluded. Of the 497
      subjects, 47 were found to belong to the SGERD group and the remaining 450 to the
      negative GERD group. RESULTS: Hiatus hernia was observed in 31.9% of the SGERD
      group and 10.9% of the negative GERD group, with the rate being significantly
      higher in the SGERD group. Esophagitis developed in 36.2% of the SGERD group and
      in 11.3% of the negative GERD group. The risk of esophagitis was significant in
      the presence of SGERD (P < 0.01), the absence of H. pylori infection (P < 0.01),
      the absence of gastric mucosa atrophy (P < 0.01), elevated triglycerides during
      the 5-year follow-up (P < 0.05), and an elevated body mass index (P < 0.05).
      Thus, even following adjustment for other factors, SGERD, with a demonstrated
      hazard ratio of 3.07, was a significant risk of reflux esophagitis. CONCLUSIONS:
      The possibility is high that the presence of SGERD is a risk factor for
      esophagitis. In particular, individuals with hiatus hernia, those without H.
      pylori infection, and those who smoke and drink alcohol are prone to develop
      esophagitis.

PMID- 16799884
TI  - Effects of melatonin or acetylsalicylic acid on gastric oxidative stress after
      bile duct ligation in rats.
AB  - BACKGROUND: Antioxidant enzyme activities decrease after bile duct ligation. The
      aim of this study was to assess the effect of melatonin and acetylsalicylic acid
      on antioxidant enzyme activities in gastric oxidative stress induced by bile duct
      ligation. METHODS: Sixty-four animals were divided into eight groups of eight
      rats each. Male Sprague-Dawley rats were subjected to either a sham operation or
      common bile duct ligation (BDL) before treatment with melatonin (MEL) or
      acetylsalicylic acid (ASA). Gastric superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx) activities, and malondialdehyde (MDA) and nitric
      oxide (NO) levels were determined by spectrophotometers and evaluated. RESULTS:
      Our results indicated that BDL caused a significant increase in lipid
      peroxidation, whereas coadministration of MEL with ASA significantly decreased
      MDA and NO levels in BDL rats. Moreover, coadministration of MEL and ASA
      increased antioxidant enzyme activities after the BDL, and these increases were
      statistically significant for CAT and GPx. On the other hand, the increase in SOD
      activity was not significant. CONCLUSIONS: Melatonin administration, either alone
      or together with acetylsalicylic acid, decreases lipid peroxidation and increases
      antioxidant enzyme activities in gastric tissues of rats after bile duct
      ligation. ASA administration, however, either alone or with a vehicle, increases
      lipid peroxidation and decreases antioxidant enzyme activities.

PMID- 16799886
TI  - Oral dimethyl sulfoxide for systemic amyloid A amyloidosis complication in
      chronic inflammatory disease: a retrospective patient chart review.
AB  - BACKGROUND: Amyloid A amyloidosis is an obstinate disease complication in chronic
      inflammatory disease, and there are few effective therapies. The objective of
      this study was to investigate the effect of oral dimethyl sulfoxide (DMSO) on
      amyloid A amyloidosis. METHODS: Fifteen secondary amyloid A amyloidosis patients
      (4 men, 11 women; age, 23-70 years) were treated with DMSO between 1995 and 2003.
      DMSO was administered orally in all patients at a dose of 3-20 g/day. The
      clinical symptoms together with the renal and gastrointestinal functions were
      evaluated before and after treatment. RESULTS: Among the 15 patients, amyloid A
      amyloidosis was a complication of rheumatoid arthritis (RA) in 10, of Crohn's
      disease in 4, and of Adult Still's disease in 1. Nine cases mainly involved the
      kidney, with renal dysfunction and proteinuria, five mainly involved the
      gastrointestinal tract, with protein-losing gastroenteropathy and intractable
      diarrhea, and one involved both gastrointestinal and renal amyloidosis. DMSO
      treatment was successful in 10 (66.7%) of the 15 patients (RA, 6/10; Crohn's
      disease, 4/4; Adult Still's disease, 0/1). Eight weeks of DMSO administration
      improved the renal function and proteinuria in five out of ten renal amyloidosis
      patients, but had no effect on those patients with severe and/or advanced renal
      dysfunction. With regard to gastrointestinal amyloidosis, gastrointestinal
      symptoms, including diarrhea and protein-losing gastroenteropathy, were improved
      in six patients. No serious side effects were encountered with the DMSO
      treatment. CONCLUSIONS: Oral administration of DMSO is an effective treatment for
      amyloid A amyloidosis, especially for gastrointestinal involvement and the early
      stage of renal dysfunction.

PMID- 16799887
TI  - Sucralfate prevents the delay of wound repair in intestinal epithelial cells by
      hydrogen peroxide through NF-kappaB pathway.
AB  - BACKGROUND: Recent studies have shown that sucralfate (SF) has therapeutic
      effects on colonic inflammation in ulcerative colitis. The aim of this study was
      to clarify the function of SF for wound repair in intestinal epithelial cells
      (IEC). METHODS: (1) Activation of signal proteins [ERK1/2 mitogen-activated
      protein kinase (MAPK), IkappaB-alpha] in IEC-6 cells after stimulation with 10(
      4) M potassium sucrose octasulfate (SOS), which is the functional element of SF,
      was assessed by Western blot. (2) Induction of transforming growth factor (TGF)
      beta1, TGF-alpha, EGF, and cyclooxygenase-2 (COX-2) mRNA after stimulation of IEC
      6 cells with SOS was assessed by reverse transcriptase-polymerase chain reaction.
      (3) IEC-6 cells were wounded and cultured for 24 h with various concentrations of
      SOS in the absence or presence of 20 microM H(2)O(2). Epithelial migration or
      proliferation was assessed by counting migrating cells or bromodeoxyuridine
      (BrdU)-positive cells across the wound border. RESULTS: (1) SOS activated IkappaB
      alpha, but it did not activate ERK1/2 MAPK. (2) SOS enhanced the expression of
      COX-2 mRNA, but it did not change the mRNA expression of other growth factors.
      (3) SOS did not enhance wound repair in IEC-6 cells, but it decreased the number
      of dead cells (maximum, 74%) (P < 0.01) in a dose-dependent manner and prevented
      the diminishment of epithelial migration (maximum, 61%) (P < 0.01) and
      proliferation (maximum, 37%) (P < 0.05) induced by H(2)O(2). These functions of
      SOS were suppressed by the NF-kappaB and COX-2 inhibitors. CONCLUSIONS: SOS
      prevented the delay of wound repair in IEC-6 cells induced by H(2)O(2), probably
      through induction of COX-2 and an anti-apoptotic mechanism. These effects of SOS
      might be given through the activation of the NF-kappaB pathway.

PMID- 16799888
TI  - Visceral fat accumulation and insulin resistance are important factors in
      nonalcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver diseases are often associated with obesity,
      insulin resistance, and excessive visceral fat accumulation. The aims of this
      study were (1) to evaluate the relationship between the severity of fatty liver
      and visceral fat accumulation in nonalcoholic fatty liver diseases, and (2) to
      investigate the relationships of fatty liver with biochemical data and insulin
      resistance. METHODS: One hundred twenty-nine subjects (63 women) with fatty liver
      diagnosed by ultrasonography were enrolled. Subjects positive for hepatitis B
      virus, hepatitis C virus, or autoimmune antibodies and those whose alcohol intake
      was over 20 g/day were excluded. The visceral fat area at the umbilical level and
      the liver-spleen ratio were evaluated by computed tomography. RESULTS: The
      severity of fatty liver evaluated by ultrasonography showed a significant
      positive relationship with the visceral fat area and waist circumstance (fatty
      liver severity: mild, 92.0 +/- 30.9 cm(2); moderate, 122.1 +/- 32.6 cm(2);
      severe, 161.0 +/- 48.4 cm(2); P < 0.0001). The visceral fat area and liver-spleen
      ratio were negatively correlated (r = -0.605, P < 0.0001). The severity of fatty
      liver showed strong positive relationships with serum aspartate aminotransferase,
      alanine aminotransferase, fasting plasma glucose, fasting plasma insulin, and
      insulin resistance. The severity of fatty liver was positively related to the
      visceral fat area in 49 nonobese subjects (body mass index <25). CONCLUSIONS: The
      severity of fatty liver was positively correlated with visceral fat accumulation
      and insulin resistance in both obese and nonobese subjects, suggesting that
      hepatic fat infiltration in nonalcoholic fatty liver disease may be influenced by
      visceral fat accumulation regardless of body mass index.

PMID- 16799890
TI  - Comparison of three methods of nutritional assessment in liver cirrhosis:
      subjective global assessment, traditional nutritional parameters, and body
      composition analysis.
AB  - BACKGROUND: Liver cirrhosis affects the results of many of the traditional
      techniques currently used to evaluate nutritional status. Our aim was to compare
      the traditional two-compartment model (subjective global assessment and
      anthropometry and blood tests) of nutritional assessment with a
      multicompartmental model (body composition analysis) in patients with cirrhosis.
      METHODS: Seventy-nine patients and 17 control subjects were studied. Subjective
      global assessment, anthropometry and blood tests, and body composition analysis
      were performed for each. The two most important compartments were body cell mass
      and total body fat. The subjects were classified by each method as well nourished
      or moderately or severely malnourished. RESULTS: Twenty-five patients (31.6%)
      were malnourished according to the subjective global assessment, 2 (6.3%) with
      Child's class A cirrhosis, 10 (34.5%) with class B, and 13 (72.2%) with class C,
      whereas 24 (30.4%) were malnourished according to the traditional model, 5
      (15.6%) in the Child's A group, 8 (27.6%) in B, and 11 (61.1%) in C. According to
      the multicompartmental model, 48 patients (60.1%) were malnourished, 11 (34.4%)
      in Child's A, 20 (69%) in B, and 17 (94.4%) in C. The use of the
      multicompartmental model increased the prevalence of malnutrition by more than
      60% in Child's classes A and B patients and by more than 20% in Child's class C
      patients. CONCLUSIONS: Traditional nutritional assessment, although easier,
      underestimated the prevalence and severity of malnutrition in patients with
      cirrhosis. The underestimation was more pronounced in Child's class A and B
      patients.

PMID- 16799889
TI  - Efficacy of interferon monotherapy in young adult patients with chronic hepatitis
      C virus infection.
AB  - BACKGROUND: Suppression of the progression to cirrhosis and hepatocellular
      carcinoma is important, especially for young hepatitis C virus (HCV)-infected
      patients. The aim of this study was to analyze the response to interferon (IFN)
      monotherapy in young HCV patients. METHODS: Between 1989 and 2002, 1021 anti-HCV
      positive patients hospitalized at Toranomon Hospital received IFN monotherapy.
      Among these patients, 144 were < or =35 years of age, while the remaining 877
      were 36-73 years old. We retrospectively identified 209 patients with known dates
      of blood transfusion (i.e., start of HCV infection) among the 1021 patients. IFN
      treatment lasted 6 months. RESULTS: HCV RNA level (P < 0.001), HCV genotype (P <
      0.001), age (P < 0.001), and liver histology (P = 0.01) were identified as
      determinants of the response to IFN monotherapy in 1021 patients. Moreover, in
      patients with high viral load and genotype 1b, the sustained virological response
      (SVR) rate was significantly higher in those aged < or =35 years than in older
      patients (P < 0.001). In patients with genotype 1b with known date of blood
      transfusion, a longer duration of infection negatively influenced the SVR rate.
      In the 209 patients, multivariate analysis identified HCV RNA level (P < 0.001),
      age (P = 0.002), and duration of infection (P = 0.049) as determinants of SVR.
      CONCLUSIONS: The response of IFN monotherapy is better in patients aged < or =35
      years than in older patients, probably because of mild stage histology, the
      effect of host-related factors, and shorter period of infection. Long-term IFN
      monotherapy may be suitable for young women who desire to become pregnant or
      those with anemia.

PMID- 16799892
TI  - Validation of the Japanese version of the Rome II modular questionnaire and
      irritable bowel syndrome severity index.
AB  - BACKGROUND: Instruments for measuring the presence and severity of specific
      irritable bowel syndrome (IBS) symptoms, comparable to those used in Western
      countries, have been lacking in Japan. The aim of this study was to develop,
      validate, and confirm the reliability of the Japanese version of the Rome II
      modular questionnaire for IBS (RIIMQ-J) and the IBS severity index (IBSSI-J).
      METHODS: Forty-nine patients in the university hospital with chronic or recurrent
      abdominal pain and discomfort and/or altered bowel habits were enrolled. With
      Rome II criteria, 27 patients were diagnosed as having IBS, and the other 22
      patients were evaluated as having other functional bowel disorders (FBDs). The
      English versions of RIIMQ and IBSSI were translated into Japanese. After back
      translation and approval of the questionnaire, subjects completed both
      questionnaires twice within 14 days. RESULTS: Cronbach's alpha of the RIIMQ-J was
      high (0.72). The sensitivity of RIIMQ-J for the diagnosis of IBS was also high
      (89%). The specificity of RIIMQ-J for denial of IBS among patients with other FBD
      was satisfactory (73%). The IBSSI-J showed high internal consistency (0.69) and
      reproducibility (intraclass correlation coefficient, 0.86, P < 0.001).
      CONCLUSIONS: The RIIMQ-J and IBSSI-J are valid, reliable, and appropriate
      instruments for detecting and assessing the severity of IBS status in Japanese
      patients.

PMID- 16799891
TI  - New approach to diagnosing ampullary tumors by magnifying endoscopy combined with
      a narrow-band imaging system.
AB  - BACKGROUND: A newly developed narrow-band imaging (NBI) system, which uses
      modified optical filters, can yield clear images of microvessels and surface
      structure in gastric and colonic diseases. In the present study, we investigated
      the ability of magnifying endoscopy with NBI (MENBI) to diagnose and
      differentiate between benign and malignant ampullary tumors. METHODS: Fourteen
      patients, whose ampullas were noted to be significantly enlarged or protruding
      with conventional endoscopy, were enrolled in the study. Specimens, which were
      obtained by forceps biopsy, endoscopic papillectomy, and/or surgery, were
      retrieved for histopathological examination. The correlation between MENBI images
      and histopathological findings was investigated. MENBI findings were classified
      as I, oval-shaped villi; II, pinecone/leaf-shaped villi; or III,
      irregular/nonstructured. In addition, tortuous, dilated, and network-like vessels
      noted on the ampullary lesions with MENBI were defined as abnormal vessels.
      RESULTS: In 6 of 14 patients, the ampullary changes were proven to be
      inflammatory in forceps biopsy specimens, without any evidence of malignancy
      after more than 1 year of follow-up. In five patients, ampullary lesions were
      treated by endoscopic papillectomy, and in three, by pancreatoduodenectomy. All
      adenomas and adenocarcinomas had type II and/or type III surface structures, and
      patients whose ampulla had a type I surface structure had only inflammatory or
      hyperplastic changes. In addition, abnormal vessels were seen only in
      adenocarcinomas and never in adenomas. CONCLUSIONS: MENBI has the ability and
      potential to predict histological characteristics of ampullary lesions.

PMID- 16799893
TI  - Intraductal papillary neoplasm of the bile duct extending superficially from the
      intrahepatic to extrahepatic bile duct.
AB  - Intraductal papillary neoplasm of the bile duct (IPNB) or liver is a recently
      noted rare disease, and its pathogenesis remains unclear. Here we present a case
      of IPNB with an interesting morphology, which was treated by resection of the
      right hemiliver and extrahepatic bile duct. A 79-year-old woman was found to have
      a high alkaline phosphatase level and slight dilatation of the right intrahepatic
      bile duct on imaging studies. The right intrahepatic bile duct became dilated
      over a 2-year period; however, no solid mass could be detected, and tumor markers
      were not elevated. Hepatic resection was scheduled because a mucin-producing bile
      duct carcinoma of the liver was suspected. A right hemihepatectomy was conducted,
      and the extrahepatic bile duct was also resected after malignant cells were found
      in the surgical stump of the right bile duct and in the bile itself.
      Macroscopically, diffuse dilatation of the intrahepatic bile duct was noted, but
      no solid component or mucin within the duct was found. Histopathological findings
      revealed carcinoma in situ, IPNB, in the majority of intrahepatic bile ducts,
      with no lymph node metastasis, and it extended continuously to the epithelium of
      the common bile duct. No tumor recurrence or biliary dilatation was observed at
      follow-up 2 years after surgery. It is important to consider malignancy in the
      presence of a dilated bile duct and in the absence of any cause of occlusion.
      Complete resection of IPNB results in a good prognosis and no recurrence.

PMID- 16799894
TI  - Minute colonic elastosis showing endoscopic features of hyperplastic polyp.

PMID- 16799895
TI  - Two cases in one family of living donor liver transplantation for homozygous
      familial hypercholesterolemia.

PMID- 16799896
TI  - Long-term effect of bezafibrate on parameters of hepatic fibrosis in primary
      biliary cirrhosis.

PMID- 16799897
TI  - Promise of definitive chemoradiotherapy for esophageal cancer balanced with late
      radiation toxicity: an old but new issue.

PMID- 16799898
TI  - Influence of melatonin and acetylsalicylic acid on lipid peroxidation and
      antioxidant enzyme activities in gastric mucosa.

PMID- 16799899
TI  - Natural history and new conceptual framework of gastroesophageal reflux disease.

PMID- 16799900
TI  - Nutritional assessment in liver cirrhosis.

PMID- 16799901
TI  - [Test-retest and interrater reliability of Barcelona Test].
AB  - INTRODUCTION: The short version of the Barcelona Test is a clinical tool that
      covers a wide spectrum of neuropsychological skills. Since its creation in 1977,
      it has often been subject of study either for its internal aspects or in
      validation studies with other cognitive tests. The results indicate that the
      Barcelona Test is a useful instrument in detecting cognitive impairment. METHOD:
      The aim of this study is to measure the testretest reliability and the interrater
      reliability of the Abbreviated Barcelona Test in normal population. SAMPLE: the
      sample consists of 31 normal subjects (14 men and 17 women) from 20 to 65 years
      old. INSTRUMENTS: Abbreviated Barcelona Test (TBA), Mini-Mental Status
      Examination (MMSE), Syndrome-Kurztest (SKT) and Interview for Deterioration of
      Daily living in Dementia (IDDD). STATISTICAL ANALYSIS: descriptive statistics and
      intraclass correlation coefficient. RESULTS: Test-retest reliability shows good
      intraclass correlation coefficients with both direct ICC=0.92 (IC 95%: 0.85-0.96)
      or typified scores ICC=0.79 (IC 95%: 0.61-0.89). Nevertheless, when each of the
      subtests is considered, correlations clearly show two characteristics: subtest
      with no or minimal range of scores and subtest with distribution of scores (as is
      the case of memory and executive function). The intraclass coefficient found for
      the interrater reliability is ICC =0.99 (IC 95 %: 0.99-0.99) and an alpha of 0.99
      which indicate excellent reliability. As a whole, the abbreviated version of the
      Barcelona Test has excellent test-retest and interrater reliability psychometric
      characteristics.

PMID- 16799902
TI  - [Rapid Disability Rating Scale-2 in Alzheimer's disease: NORMACODEM project
      data].
AB  - INTRODUCTION: The study aimed to investigate the Rapid Disability Rating Scale-2
      (RDRS-2) in Alzheimer's disease (AD). Test retest reliability, internal
      consistency, data of discriminant validity of the scale, correlations with other
      functional and cognitive measures were analyzed. MATERIAL AND METHODS: 451
      subjects were assessed: 254 healthy controls, 86 with cognitive impairment but no
      dementia (CIND) and 111 subjects diagnosed of AD. Total and subscales scores of
      the RDRS-2 were obtained. The total score is the sum of three subscales:
      activities of daily living, disability, and special problems. To establish its
      correlation with other functional scales and cognitive instruments, the following
      tools were applied: Blessed Dementia Rating Scale (BDRS), Interview for the
      Deterioration of Daily Living in Dementia (IDDD), Alzheimer's Disease Assessment
      Scale-Cognitive (ADAS-Cog) and the Mini-Mental State Examination (MMSE).
      STATISTICAL ANALYSIS: lineal multivariate regression analysis. Crossvalidation.
      ROC curves. Intraclass coefficient. Cronbach's alpha and Pearson's Correlation
      coefficient. RESULTS: RDRS-2 scores by group were the following (mean and SD):
      Controls (18.95; 1.64), CIND (20.61; 2.88), and AD (28.96; 9.07). Results from
      regression analysis 282 demonstrated absence of influence of sociocultural
      variables such as age and education in RDRS-2 scores. Correlations with other
      instruments were as following: BDRS, r=0.820; IDDD, r=0.882; ADAS-Cog, r=0.762,
      and MMSE, r=0.742. Intraclass coefficient was 0.86 and Cronbach's alpha was 0.91.
      For the RDRS-2 the best cutoff score was 21 (82.88% sensitivity and 88.8%
      specificity). Area under the ROC curve was 0.92. CONCLUSIONS: The Spanish
      adaptation of the RDRS-2 is free of sociocultural influence, and shows very
      adequate data on internal consistency and stability. Although not specifically
      designed for its use in AD it correlates highly and significantly with other
      functional scales as well as with the degree of cognitive impairment in AD.

PMID- 16799903
TI  - [Observational study on safety, tolerability and effectiveness of galantamine in
      patients with mild to moderately severe Alzheimer's disease].
AB  - INTRODUCTION: Several controlled clinical trials have demonstrated safety,
      tolerability, and efficacy of galantamine in patients with Alzheimer's disease
      (AD). We present an observational and multicenter study carried out in Spain. Its
      main objective was the assessment of the safety and tolerability of galantamine
      in the treatment of mild to moderately severe dementia of the Alzheimer type
      under real clinical conditions. METHODS: The study had five visits over a 6-month
      period. Titration of galantamine was performed on a standard basis. All the
      adverse events (AE) reported were recorded. Serious AE were particularly
      considered. Effectiveness was also assessed covering cognitive, functional,
      behavioral and sleep domains. RESULTS: 723 patients were enrolled but 74 were
      excluded, a sample of 649 (71% women and 29% men) remaining. A total of 56.3%
      patients completed all visits. Baseline Mini-Mental mean score was 19,4 (SD:
      4,7). Up to 400 AEs were collected from 29.3% of the patients. The commonest AEs
      were: nausea (9.7%), vomiting (7.1%), dizziness (4.6%), and diarrhea (4.5%). Mini
      Mental scores were stable over time and favorable and significant differences in
      behavioral and sleep evaluations were observed. CONCLUSIONS: Galantamine is a
      safe and well-tolerated treatment, and provides cognitive, functional, and
      behavioral benefits in patients with mild to moderately severe AD.

PMID- 16799905
TI  - [Cyclic alternating pattern as a sign of brain instability during sleep].
AB  - During the last 20 years, the fact that the role of microarousal arousal is very
      involved in the pathophysiology of sleep disorders has been widely demonstrated.
      However, in spite of this, the nature of microarousal is still under debate. The
      awakening system forms a part of the relationship between activation system and
      sleep maintenance, thus providing the natural evolution of sleep and defending it
      from the stimuli of the external world. The awakening system, that includes the
      concept of microarousal, can appear isolated or periodically, then receiving the
      name of cyclic alternating pattern (CAP). CAP may be affected by different
      factors that can alter its periodicity, thus offering quantitative information on
      sleep instability. It can also serve as another new tool to understand human
      sleep and as complementary information supplied by the sleep macrostructure and
      microarousal study. This study aims to explain the concept of CAP and its
      pathophysiology studied up to the present.

PMID- 16799904
TI  - [Evidence of facial palsy and facial malformations in pottery from Peruvian Moche
      and Lambayeque pre-Columbian cultures].
AB  - INTRODUCTION: Moche (100-700 AD) and Lambayeque-Sican (750-1100 AD) are pre
      Columbian cultures from Regional States Period, developed in Northern Peru.
      Information about daily life, religion and medicine has been obtained through the
      study of Moche ceramics found in lords and priests tombs, pyramids and temples.
      OBJECTIVE: To analyze archeological evidences of Moche Medicine and neurological
      diseases through ceramics. MATERIAL AND METHODS: Representations of diseases in
      Moche and Lambayeque iconography and Moche pottery collections exposed in
      Casinelli museum from Trujillo, and Bruning National Archeological museum from
      Lambayeque, Peru, were studied. The most representative cases were analyzed and
      photographed, previous authorization from authorities and curators of the
      museums. RESULTS: The following pathologies were observed in ceramic collections:
      peripheral facial palsy, facial malformations such as cleft lip, hemifacial
      spasm, legs and arm amputations, scoliosis and Siamese patients. Male and females
      Moche doctors were also observed in the ceramics in ritual ceremonies treating
      patients. CONCLUSIONS: The main pathologies observed in Moche and Lambayeque
      pottery are facial palsy and cleft lip. These are one of the earliest registries
      of these pathologies in pre-Columbian cultures in South-America.

PMID- 16799906
TI  - [Reader's syndrome in carotid disection with response to antiepileptic drugs].

PMID- 16799907
TI  - [NMO-IgG antibodies in neuromyelitis optica: a report of 2 cases].
AB  - INTRODUCTION: Neuromyelitis optica is an inflammatory demyelination disease that
      selectively affects optic nerves and spinal cord. Recently it has been described
      that the NMO-IgG antibodies, are highly specific for the diagnosis, although they
      are also present in partial forms of the disease. The antigen responsible for
      this immune response seems to be aquaporin-4 water channel. CLINICAL CASE: We
      describe the detection in our laboratory of NMO-IgG antibodies in two patients,
      one of them with a neuromyelitis optica and the other one with a recurrent
      myelitis and subclinical involvement of the optic nerve. CONCLUSIONS: By using
      dual immunostaining, confocal microscopy showed that the antibodies of both
      patients colocalized with that of an anti-aquaporin-4.

PMID- 16799908
TI  - [Anoxic encephalopathy after ultraviolet radiation session: follow-up and
      results].
AB  - Anoxic encephalopathy is the consequence of acute cerebral oxygen deprivation
      usually generated by cardiac arrest and/or respiratory failure. Recently an
      interesting case of one patient with cerebral anoxia after ultraviolet radiation
      session has been published. This paper shows the clinical evolution of this
      patient after inclusion in a multidisciplinary rehabilitation program, which
      included treatment of the psychopathological, neuropsychological and functional
      impairments that this pathology often generates. Over successive decades cerebral
      anoxia has come to be identified principally as one of the most significant
      causes of an isolated amnesia syndrome. Our patient presented at baseline intense
      difficulties in every verbal and visual memory processes associated with moderate
      impairments in sustained, selective and shifting attention as well as temporal
      disorientation. Compensation of memory deficit was the main rehabilitation
      strategy used in this case. This rehabilitation approach was possible thanks to
      the high degree of self-awareness of memory deficits shown by the patient and the
      selective impairment of memory with partial preservation of the rest of cognitive
      functions. This particular case gives us the opportunity to show the
      multidisciplinary approach of cognitive rehabilitation and the process of
      reintegration to social activities and to productive work even when deficits
      persist.

PMID- 16799909
TI  - [Afibrinogenemia: description of a case with recurrent intracranial bleeding].
AB  - INTRODUCTION: Congenital afibrinogenemia is a very rare autosomal recessive
      disorder of the coagulation. The lack of fibrinogen makes the blood inclotting
      and patients suffer from bleeding at a minimal trauma. It is usually noticed
      within the first few days of life because of the umbilical cord bleeding.
      Intracerebral hematoma is infrequent. CASE DESCRIPTION: 46-year-old woman who
      suffers from congenital afibrinogenemia and has five episodes of intracerebral
      bleeding, all of them in the posterior circulation. As a complication, she also
      presents an epilepticus status and the therapy with concentrated fibrinogen
      caused pulmonary thromboembolism. CONCLUSIONS: After analysing the cases
      described in literature, there are evidences that the majority of the
      intracerebral hematoma are located in the posterior circulation. A few patients
      developed major thomboemolisms following infusion with concentrated fibrinogen
      and there are only isolated descriptions of beneficial prophylactic effects. So,
      it is would necessary studies more extensive research to achieve effectiveness in
      the prevention of the bleeding.

PMID- 16799911
TI  - [Inversion of the sign or signal of the cross].

PMID- 16799910
TI  - [Evolution until death of two members of a family with A3243G mutation and MELAS
      phenotype versus diabetes mellitus].
AB  - INTRODUCTION: The A3243G gene tRNALeu(UUR) mutation has different phenotypic
      expressions. The clinical outcome and survival of each phenotype are mostly
      unknown. We followed-up two of three family members, carriers of the A3243G
      mutation, until their death. CLINICAL CASE: The proband case had MELAS
      (mitochondrial myopathy, encephalopathy, lactacidosis, stroke) phenotype.
      Although he presented with a stroke-like episode, he developed recurrent
      generalized and partial epileptic seizures without associated stroke-like
      episodes over time as well as slowly progressive dementia. The cognitive
      performance greatly worsened after a complex partial epileptic status. He died
      from bronchopneumonia and septic shock eleven years after diagnosis. His sister
      remains asymptomatic. His mother was diagnosed of diabetes mellitus and deafness
      when she was 53. Seventeen years later she developed a single stroke-like
      episode. She died one year after from acute renal failure and cardiogenic shock
      following sympathectomy for ischemic angiopathy. In the MELAS case neither
      idebenone treatment nor valproate substitution by other anticonvulsants reduced
      seizure frequency nor the spreading of lesions evaluated by MRI. In the phenotype
      with diabetes and deafness the outcome diabetes mellitus was as expected.
      CONCLUSIONS: In this family with A3243G mutation, the phenotype with
      neurosensorial deafness and diabetes mellitus seems to have longer survival than
      the MELAS phenotype. The cause of death in both cases was closely related to
      medical complications prevalent in each patient at the time of death.

PMID- 16799912
TI  - Colpocephaly: a case report.
AB  - Colpocephaly is an abnormal enlargement of the occipital horn of the lateral
      ventricle, also described as persistence of the fetal configuration of the
      lateral ventricles. Since it was first described, colpocephaly has been found in
      association with several abnormalities of the brain. Various etiologies have been
      postulated, including intrauterine/perinatal injuries, genetic disorders, and an
      error of morphogenesis. We report a new case of colpocephaly associated with
      absence of the corpus callosum and review the literature.

PMID- 16799913
TI  - Advanced maternal age is an independent risk factor for intrauterine growth
      restriction.
AB  - Reports on the association between advanced maternal age (AMA) and intrauterine
      growth restriction (IUGR) are conflicting. Our objective was to determine if AMA
      is an independent risk factor for IUGR. Our case-control study compared cases
      with IUGR (birthweight<10th percentile for gestational age) and a control group
      without IUGR. Gestational ages were all confirmed by ultrasound. The study
      included only singletons and fetal anomalies were excluded. Both groups were
      evaluated for maternal demographics and clinical risk factors. AMA was defined as
      maternal age>35 years. Univariate and multivariate analyses were used to examine
      associations. During the study period, there were 824 cases with IUGR meeting the
      inclusion criteria; these were compared with 1648 controls (no IUGR) randomly
      selected from the same population during the same study period. The significant
      factors associated with IUGR multivariate analyses were black race (odds ratio
      [OR], 22.4; 95% confidence interval [CI], 17.8 to 28); chronic hypertension (OR,
      2.2; 95% CI, 1.5 to 3.2); pregestational diabetes (OR, 3.3; 95% CI, 1.6 to 7)
      illicit drug use (OR, 3.3; 95% CI, 2.2 to 5.2), and AMA (OR, 1.4; 95% CI, 1.1 to
      1.8). There was a positive dose-response association between increasing maternal
      age and increasing risk for IUGR. At maternal age of 40 years or older, the OR
      and 95% CI for IUGR was 3.2 and 1.9 to 5.4, respectively. AMA is an independent
      risk factor for IUGR. Our findings suggest that screening for IUGR is indicated
      in women age 35 years or older.

PMID- 16799914
TI  - Gestational therapy with an angiotensin II receptor antagonist and transient
      renal failure in a premature infant.
AB  - The fetotoxic effects of angiotensin converting enzyme inhibitors when used
      during the second half of pregnancy are well known. The more recently developed
      angiotensin II receptor antagonists appear to yield similar fetal abnormalities.
      We report a premature infant born to a 41-year-old mother with a long history of
      infertility who had received losartan therapy for hypertension throughout an
      undetected pregnancy. Ultrasound examination 2 days prior to delivery identified
      a single fetus at 29 weeks gestation, anhydramnios, and an empty fetal bladder.
      The neonatal course was complicated by oliguria, hyperkalemia, marked renal
      dysfunction, respiratory failure, joint contractures, and a large anterior
      fontanelle with widely separated sutures. Hypotension (mean arterial pressure<25
      torr) on day 1 responded to volume expansion, dopamine, and hydrocortisone. Serum
      creatinine reached a maximum of 2.7 mg/dL on day 6 and decreased to 0.4 by day
      56. No formal urinalysis was performed, but the urine was reported to be visually
      clear throughout the course. Although a renal ultrasound on day 2 was normal, a
      follow-up study at 7 months revealed bilateral generalized parenchymal
      echogenicity, consistent with medical renal disease. Since then, weight and
      length have been at the 5th percentile or less, with apparent renal tubular
      acidosis necessitating the addition of sodium citrate supplements. This case
      emphasizes the importance of maintaining a high index of suspicion for potential
      pregnancy when contemplating the use of a drug of this class, and considering
      serial testing for pregnancy when using such drugs, even in patients with a
      longstanding history of infertility.

PMID- 16799915
TI  - Methadone metabolism by early gestational age placentas.
AB  - The objective of this study was to identify the enzyme that metabolizes methadone
      in preterm placentas. Microsomal fractions were obtained from preterm (17 to 34
      weeks) placentas (36 total; 12 per each gestational age group) and their activity
      in metabolizing methadone to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
      (EDDP) was determined. The enzyme catalyzing the reaction was identified by using
      chemical inhibitors selective for various cytochrome P450 isozymes and monoclonal
      antibodies raised against them. The metabolism of methadone by microsomes
      revealed saturation kinetics. Methadone was N-demethylated to EDDP by aromatase.
      The affinity of methadone to aromatase (apparent Km) did not change with
      gestation, but the activity of the enzyme (Vmax) increased and varied widely
      between individual placentas. Aromatase/CYP19 is the placental enzyme
      metabolizing methadone during pregnancy. The variability in enzyme activity among
      individuals should be reflected by the concentration of methadone in the fetal
      circulation and might be one of the factors affecting the incidence and intensity
      of neonatal abstinence syndrome.

PMID- 16799916
TI  - Changing patterns of drug utilization in a neonatal intensive care population.
AB  - Newborns in the neonatal intensive care unit (NICU) typically are exposed to a
      large number of drugs and are especially vulnerable to adverse drug reactions. It
      is important to review changes in drug use patterns periodically in the NICU to
      identify newly introduced drugs as well as drugs with increasing use. The
      objective of this study was to determine the changes in drug utilization patterns
      over a 7-year period in an NICU population. Drug utilization of 2332 neonates
      treated at an intramural NICU between January 1, 1997 and December 31, 1998, and
      2691 neonates between January 1, 2001 and June 30, 2004 was analyzed using chi
      square tests, T tests, and linear regression. There was an increased utilization
      of antibiotics, central nervous system drugs, endocrine agents, cardiovascular
      and gastrointestinal drugs, and a decreased utilization of ophthalmic drugs. No
      changes in nutritional, biological, renal, and pulmonary drugs were observed.
      Some individual drug changes include an increased use of vancomycin, cefepime,
      caffeine, and a decreased use of morphine. Significant changes in drug
      utilization patterns in an NICU were observed during a 7-year period. These data
      are useful in monitoring drug resistance patterns, adverse drug reactions, and
      prioritizing areas of relevant therapeutic research and educational programs.

PMID- 16799917
TI  - Maternal exposure to endocrine-active substances and breastfeeding.
AB  - Women pass on low levels of hazardous environmental contaminants and naturally
      occurring substances during pregnancy and nursing. In addition to estrogenic
      activity, these substances exhibit antiestrogenic, antiandrogenic, and androgenic
      actions, and because they can affect thyroid metabolism, they are described as
      endocrine-active substances (EAS). Specific topics related to EAS metabolism by
      mothers, fetuses, and infants are discussed. There is strong evidence that the
      assumed risk of EAS in early human development is exacerbated by interrupting
      neonatal priming provided by breastfeeding. The benefits of breastfeeding are
      fundamental to attenuate possible EAS effects on infants due to long-term
      intrauterine exposure. Breastfeeding is a guarantor of health benefits, whereas
      its alternative (infant formula) is a predictor of some health limitations.
      Mothers concerned with exposure to environmental contaminants should be advised
      of the proven benefits of breastfeeding and the possible health limitations of
      formula feeding.

PMID- 16799918
TI  - High C-reactive protein levels during a benign neonatal outbreak of echovirus
      type 7.
AB  - Literature associates neonatal enteroviral infections with high morbidity and
      mortality. The literature also suggests that high C-reactive protein (CRP) levels
      are indicators of bacterial infection. We report on high CRP levels, not due to
      bacterial infection, during an outbreak of neonatal echovirus type 7 infections
      in the fall of 2002, which had no major complications or mortality.

PMID- 16799919
TI  - Is testing for cytomegalovirus and cystic fibrosis indicated in members of a
      nonwhite pregnant population in whom the fetus has an echogenic bowel?
AB  - The purpose of this study was to determine whether testing for cystic fibrosis
      (CF) and cytomegalovirus (CMV) infection is necessary in African-American and
      Hispanic gravidas in whom the fetus had an echogenic bowel. This retrospective
      study consisted of only African American and Hispanic patients in whom the fetus
      had an echogenic bowel, referred to the Maternal and Fetal Medicine unit at New
      Jersey Medical School for a specialized ultrasound, between June 30, 2004, and
      March 31, 2005. Sixty-five patients met the inclusion criteria for our study.
      Maternal serum testing for CF was done in 32 patients and all newborns were
      screened for the disease. There were no positive results for CF. CMV serology was
      tested in 38 patients and there were no cases of acute congenital CMV infection.
      In our population of 65 patients, there was one intrauterine growth restricted
      (IUGR) fetus and five intrauterine fetal demise (IUFD). Although all patients who
      were tested for CMV infection tested negative, the true incidence in our selected
      population may be underestimated because some of our patients were not tested.
      There were no cases of congenital CMV infection and all newborn screening tests
      for CF were negative. Prenatal diagnosis of fetal echogenic bowel was associated
      with a 7.6% incidence of IUFD and 1.6% incidence of IUGR.

PMID- 16799920
TI  - Statin therapy induces ultrastructural damage in skeletal muscle in patients
      without myalgia.
AB  - Muscle pain and weakness are frequent complaints in patients receiving 3
      hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many
      patients with myalgia have creatine kinase levels that are either normal or only
      marginally elevated, and no obvious structural defects have been reported in
      patients with myalgia only. To investigate further the mechanism that mediates
      statin-induced skeletal muscle damage, skeletal muscle biopsies from statin
      treated and non-statin-treated patients were examined using both electron
      microscopy and biochemical approaches. The present paper reports clear evidence
      of skeletal muscle damage in statin-treated patients, despite their being
      asymptomatic. Though the degree of overall damage is slight, it has a
      characteristic pattern that includes breakdown of the T-tubular system and
      subsarcolemmal rupture. These characteristic structural abnormalities observed in
      the statin-treated patients were reproduced by extraction of cholesterol from
      skeletal muscle fibres in vitro. These findings support the hypothesis that
      statin-induced cholesterol lowering per se contributes to myocyte damage and
      suggest further that it is the specific lipid/protein organization of the
      skeletal muscle cell itself that renders it particularly vulnerable.

PMID- 16799921
TI  - TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and
      Loeys-Dietz syndrome.
AB  - Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder
      characterized by manifestations in the cardiovascular, skeletal, ocular, and
      other organ systems. MFS type1 (MFS1) is caused by mutations in the gene encoding
      fibrillin (FBN1). Recently, the transforming growth factor-beta receptor-2 gene,
      TGFBR2, has been shown to be associated with a second type of this disorder with
      typically mild or absent ocular involvement (MFS type 2; MFS2). Several point
      mutations were found in the highly conserved serine/threonine kinase domain of
      TGFBR2. Mutations in both TGFBR1 and TGFBR2 are associated with Loeys-Dietz
      aortic aneurysm syndrome (LDS). We searched for TGFBR1 and TGFBR2 mutations in 41
      unrelated patients fulfilling the diagnostic criteria of Ghent nosology or with
      the tentative diagnosis of Marfan syndrome, in whom mutations in the FBN1 coding
      region were not identified. In TGFBR1, two mutations and two polymorphisms were
      detected. In TGFBR2, five mutations and six polymorphisms were identified.
      Reexamination of patients with a TGFBR1 or TGFBR2 mutation revealed extensive
      clinical overlap between patients with MFS1, MFS2, and LDS.

PMID- 16799923
TI  - Lipophilicity characterization of new N-phenylamino-azaspiranes as potential
      anticonvulsant agents.
AB  - The lipophilicity of a library of N-phenylamino-2-azaspiro[4.4]nonane- and
      [4.5]decane-1,3-dione derivatives has been determined by reversed-phase thin
      layer chromatography with n-propanol-Tris buffer (pH 7.4) mixtures as mobile
      phases. Examination of chromatographic behaviour revealed a linear correlation
      between R(M) values and the concentration of n-propanol in the mobile phase. The
      partition coefficients (logP) were also calculated by use of the PrologP module
      of the Pallas computer program. Comparison of R(M0) values and calculated
      (logP(PALLAS)) data revealed the correlation expressed by the equation:
      logP(PALLAS) = 0.9995 R(M0) + 1.3451 (n = 28; r = 0.8971; F = 107.13; p < 0.05).
      The role of the lipophilicity in the anticonvulsant activity of a set of
      compounds examined is discussed: the active anticonvulsants were less lipophilic
      than inactive ones.

PMID- 16799922
TI  - Father-to-daughter transmission of Cornelia de Lange syndrome caused by a
      mutation in the 5' untranslated region of the NIPBL Gene.
AB  - Cornelia de Lange syndrome (CdLS; also called Brachmann de Lange syndrome) is a
      developmental disorder characterized by typical facial dysmorphism, growth and
      mental retardation, microcephaly, and various malformations. Mutations in the
      NIPBL gene have been identified in approximately 40% of reported cases,
      suggesting either genetic heterogeneity or that some NIPBL mutations are not
      detected by current screening strategies. We screened a cohort of 21 patients
      with no previously identified NIPBL anomaly for mutations in the 5' untranslated
      region (5'UTR) and the proximal promoter of the NIPBL gene. We identified a
      heterozygous deletion-insertion mutation in exon 1, 321 nucleotides upstream of
      the translation initiation codon (c.-321_-320delCCinsA) in one affected girl and
      her mildly affected father. This mutation altered highly conserved nucleotides,
      was not found in 400 control alleles, arose de novo in the father, and
      cosegregated with the disease in the family. Using real-time quantitative PCR, we
      showed that NIPBL mRNA expression was lowered in patients' lymphocytes compared
      to control samples. Finally, we showed that, when subcloned into a luciferase
      reporter vector, the mutation leads to a significant reduction of reporter gene
      activity. Our results demonstrate that mutations in the 5' noncoding region of
      the NIPBL gene can be involved in the pathogenesis of CdLS. Mutations affecting
      this region of the gene might be associated with a milder phenotype.

PMID- 16799924
TI  - Evidence of a flip-flop phenomenon in acamprosate pharmacokinetics: an in vivo
      study in rats.
AB  - The pharmacokinetics of acamprosate were examined in the rat after oral and
      intravenous administration in order to detect the possible presence of a flip
      flop phenomenon. Rats received 9.3 or 73.3 mg/kg of the drug as an intravenous
      bolus. The same doses were orally administered via gastric intubation. Plasma
      samples were taken from the jugular vein for determination of acamprosate
      concentration by liquid scintillation counting. The drug content was also
      quantified in urine and faeces. The acamprosate bioavailability was close to 20%,
      the amount recovered in the faeces being around 80% of the administered dose. The
      terminal slope of the oral plasma curve was significantly lower than that
      obtained after intravenous administration of the drug at both doses tested (p<2 x
      10(-6) in both cases). Moreover, the downward slope after oral administration
      (lambda2=0.006 +/- 0.001 min(-1)) practically coincided with the first-order
      absorption rate constant, previously reported by us, obtained using an in situ
      rat gut technique. It is concluded that the acamprosate absorption rate is
      considerably slower than its elimination rate so that the drug exhibits flip-flop
      pharmacokinetics after oral administration. The lower intrinsic first-order
      absorption rate constant, ka, is responsible for this phenomenon.

PMID- 16799925
TI  - Elimination of rutaecarpine and its metabolites in rat feces and urine measured
      by liquid chromatography.
AB  - Rutaecarpine is an alkaloid isolated from the medicinal herb Evodia rutaecarpa.
      This study was to evaluate the elimination pathway of rutaecarpine in rat feces
      and urine. Rutaecarpine and its metabolites (3-, 10-, 11- and 12
      hydroxyrutaecarpine) in urine were measured after incubation with beta
      glucuronidase. After the rutaecarpine was administered (25 and 100 mg/kg) orally
      to rats, the urine and fecal samples were collected using a metabolic cage for
      five consecutive days. For determining rutaecarpine, the mobile phase consisted
      of acetontrile-10 mM NaH(2)PO(4) (60:40, v/v, pH 4.2 adjusted with
      orthophosphoric acid) with a flow rate of 1 mL/min. The calibration curve was
      linear in concentrations of 0.05-50 microg/mL in fecal and urine sample. The
      results indicated that more than 42% of the rutaecarpine was excreted by feces
      after oral administration (25 and 100 mg/kg), but only a small amount of
      rutaecarpine was detected in urine at a higher dose of rutaecarpine (100 mg/kg).
      After incubation with beta-glucuronidase, the hydroxyrutaecarpine in urine was
      eluted using methanol-acetonitrile-0.04% formic acid (6:30:64, v/v) with a flow
      rate of 1.2 mL/min. We conclude that the metabolic pathway of rutaecarpine went
      through phase I hydroxylation and phase II conjugation, and the major metabolite
      is 10-hydroxyrutaecarpine eliminated from urine of the rat.

PMID- 16799926
TI  - Determination of antihyperglycemic biguanides in serum and urine using an ion
      pair solid-phase extraction technique followed by HPLC-UV on a
      pentafluorophenylpropyl column and on an octadecyl column.
AB  - An HPLC-UV method was established for the determination of metformin and buformin
      in biological fluids. Metformin was not retained on particles packed in
      conventional solid-phase extraction cartridges; in contrast, buformin was
      retained too firmly and not eluted with a solvent for recovery. However, both
      drugs were retained on particles that had been treated with an ion-pair reagent
      of heptanesulfonate or dodecylsulfate and recovered almost completely. The
      recovered fraction was subjected to HPLC on a pentafluorophenylpropyl column
      which was suitable for the determination of both biguanides in serum and in
      urine. Limits of quantitation were low enough for clinical use, and
      reproducibility was high with an RSD of 0.9-2.3%. HPLC on a conventional
      octadecyl column was suitable only for the determination of buformin in serum
      since interfering peaks appeared on the chromatograms of urine samples. The
      method was applied to analysis of some clinical specimens.

PMID- 16799927
TI  - Determination of active constituents in Lonicera confusa DC. by capillary
      electrophoresis with amperometric detection.
AB  - A method based on capillary electrophoresis with amperometric detection has been
      developed for the determination of luteolin, chlorogenic acid, 3,5
      dicaffeoylquinic acid and caffeic acid in the dried flower buds, leaves and stems
      (three medicinal parts) of Lonicera confusa DC., respectively. The effects of
      several important factors such as detection potential, the concentration of the
      running buffer, separation voltage and injection time were investigated to
      acquire the optimum conditions. The detection electrode was a 300 microm diameter
      carbon disc electrode at a working potential of + 0.90 V (vs saturated calomel
      electrode). The four analytes can be well separated within 10 min in a 40 cm-long
      fused silica capillary at a separation voltage of 12 kV in a 50 mM borate-25 mM
      phosphate buffer (pH 8.0). The relationship between peak current and analyte
      concentration was linear over about 3 orders of magnitude with detection limits
      (S/N = 3) ranging from 0.35 to 0.52 microM for all analytes. The proposed method
      has been successfully applied to the monitoring of bioactive constituents in the
      real plant samples with satisfactory assay results.

PMID- 16799928
TI  - Verified predominance of slow acetylator phenotype N-acetyltransferase 2 (NAT2)
      in a Hmong population residing in Minnesota.
AB  - Southeast Asians known as the Hmong have a high prevalence of tuberculosis and
      select cancers. The slow acetylation (SA) phenotype for N-acetyltransferase 2
      (NAT2) has been associated with toxicity from the anti-tuberculosis drug,
      isoniazid and in increased risk of select cancers. Previous research indicates a
      74.5% prevalence of SA in Hmong which differs from other Asian populations
      including the Japanese and Thai (range: 7%-45%). Given this contrast, the purpose
      of this study was to confirm or refute this unexpected predominance of the SA
      phenotype in Hmong. Unrelated, Minnesota Hmong between 18 and 65 years of age
      consented and participated by ingesting caffeine as the probe for NAT2. A urinary
      caffeine metabolic ratio AFMU/1X (<0.6) was used to classify subjects as slow
      acetylators. Among 51 analysable samples provided by 61 enrollees (27 male, 33
      female, 1 sex unknown, age 30+/-11 years [mean+/-SD]) there were 47 (92.2%) slow
      and 4 (7.8%) rapid acetylators. The prevalence of the SA phenotype (92.2%) from
      this study exceeds the 74.5% (p<0.02 by chi-square test) previously noted in
      Minnesota Hmong (n=98). The predominance of the SA phenotype within Minnesota
      Hmong is confirmed. Further studies evaluating this unexpected prevalence, its
      genetic basis and potential clinical relevance to drug toxicity and disease are
      warranted.

PMID- 16799929
TI  - Liquid chromatographic assay for the non-peptidic protease inhibitor tipranavir
      in plasma.
AB  - Tipranavir is the most recently introduced protease inhibitor for the suppression
      of the human immunodeficiency virus (HIV). A selective reversed-phase liquid
      chromatographic assay, previously developed for atazanavir, has been extended and
      validated for tipranavir in plasma. Compounds were isolated from a 500 microL
      plasma sample using liquid-liquid extraction with dichloromethane. After
      evaporation and reconstitution of the extract the sample was analysed using
      reversed-phase liquid chromatography and ultra violet detection at 280 nm. In the
      evaluated concentration range (0.2-50 microg/mL tipranavir), intra-day precisions
      were <or=8% and inter-day precisions were <or=10%. Accuracies between 95 and 108%
      were found. The clinical applicability of the assay was demonstrated in an HIV
      infected patient who ingested 500 mg tipranavir bid in combination with 100 mg
      ritonavir.

PMID- 16799930
TI  - Comparison of supercritical fluid chromatography and liquid chromatography for
      the separation of urinary metabolites of nobiletin with chiral and non-chiral
      stationary phases.
AB  - Nobiletin (NOB), a polymethoxylated flavone found in sweet orange (Citrus
      sinensis) peel, is currently recognized as a promising anti-inflammatory and anti
      tumor agent. It is believed that, by undergoing metabolic biotransformation in
      vivo, nobiletin is demethylated by hepatic P450 enzymes, yielding multiple
      hydroxylated metabolites. However, it has not been possible to date to separate
      the two demethylated nobiletin metabolites, 3'-demethyl-NOB and 4'-demethyl-NOB
      (regio-isomers) on reversed-phase liquid chromatography (RPLC). Additionally,
      both display similar mass spectrometric fragmentation, resulting in difficulties
      to identify the dominant metabolite. A successful separation method was developed
      by utilizing supercritical fluid chromatography (SFC) with chiral stationary
      phase. The separation was also attempted with normal-phase liquid chromatography
      (NPLC) in both chiral and non-chiral modes. Chromatographic separation for the
      two nobiletin metabolites was superior by SFC than by LC, especially using chiral
      stationary phase. By comparing the SFC profile of the synthesized standards, the
      major nobiletin metabolite in mouse urine was identified as 4'-demethyl-NOB, with
      the concentration of 28.9 microg/mL.

PMID- 16799931
TI  - The uptake behaviors of kaempferol and quercetin through rat primary cultured
      cortical neurons.
AB  - The objective of this study was to investigate whether kaempferol and quercetin
      could be transported into primary cultured cerebral neurons, to establish a
      practical HPLC method with UV detection for the two flavonols in the neurons, and
      to study the uptake and transport behaviors of them through the neurons. The
      present results showed that the level of kaempferol in the neurons increased
      linearly and then reached a plateau with incubation time at the high
      concentration of 10 microg/mL, but not at the other two concentrations of 1 and
      0.1 microg/mL. However, the levels of quercetin in the neurons were not detected
      at the three incubating concentrations, and there was a new peak detected in the
      cell whose retention time was shorter (3.42 min) than that of quercetin (4.65
      min). This phenomenon suggested that quercetin might be transported into the
      neurons and then metabolized quickly to some derivative. Kaempferol could be
      transported into the neurons in a concentration- and time-dependent manner when
      the neurons were incubated with the culture medium containing kaempferol at the
      high dose. There was an apparent correlation between the concentrations of
      kaempferol in the medium and in the cell, indicating that the uptake of
      kaempferol in the cell increased along with its dose (10 microg/mL). However,
      there was a negative correlation between the concentrations of quercetin in the
      medium and in the cell. The results suggested that kaempferol and quercetin were
      disposed by the neurons at different way, and this might be an important factor
      for their different effects on primary cultured cortical cells.

PMID- 16799932
TI  - Application of microdialysis to study the in vivo release of pingyangmycin from
      in situ gels in rabbits.
AB  - Microdialysis was used together with HPLC to monitor the local concentration of
      pingyangmycin hydrochloride (PYM) after embolizing rabbit ear-veins with an
      injectable sustained release formulation, PYM-Zein/PYM-Zein-sucrose acetate
      isobutyrate (SAIB), in situ gel. The dialysis probe was perfused at 2 microL/min.
      The in vivo recovery was 46.6 3.1% (n = 4). The samples were injected directly
      into HPLC. PYM was detected using UV detector at 291 nm. Separation from other
      components in the dialysate was performed using a Discovery((R)) RP-Amide C(16)
      column within 12 min. The response for PYM in the dialysate was linear (r(2) >
      0.996) over the range of 2.5-212 microg/mL. The limit of detection and limit of
      quantitation of PYM in the dialysate were 0.4 and 1.5 microg/mL, respectively.
      The results demonstrated that the in situ gel of PYM-Zein-SAIB could extend the
      release of PYM to 4 days. SAIB could significantly cut down the initial burst of
      PYM from the in situ gels (p < 0.05).

PMID- 16799933
TI  - Direct determination of nucleosides in the urine of patients with breast cancer
      using column-switching liquid chromatography-tandem mass spectrometry.
AB  - We developed an analytical method for a simple, sensitive and simultaneous
      determination of oxidized nucleosides in urine using column-switching liquid
      chromatography-electrospray/tandem mass spectrometry (LC-ESI/MS/MS). We connected
      two columns through a six-way switching valve and effectively separated
      nucleosides in the urine from the interference by column-switching liquid
      chromatography. We monitored separated nucleosides using positive ionization
      tandem mass spectrometry in selective reaction monitoring (SRM) mode. The
      calibration ranges of nucleosides were 0.2-100 nmol/mL. The linearity of the
      method was 0.994-0.999, and the limits-of-detection (LOD) at a signal-to-noise
      (S/N) ratio of 3 were 0.1-0.2 nmol/mL. The coefficients of variation were in the
      range 2.28-11.74% for within-day variation and 4.36-11.15% for day-to-day
      variation, respectively. To explore the relationship between breast cancer and
      the nucleosides level in human urine, we measured the concentrations of
      nucleosides in female patients with breast cancer (n = 30) and in normal female
      subjects (n = 30). The concentration of nucleosides was significantly increased
      in patients with breast cancer when compared with the normal controls (1
      methyladenosine; p < 0.005, N(2),N(2)-dimethylguanosine; p < 0.01, 5
      hydroxymethyl-2'-deoxyuridine; p < 0.001, 8-hydroxy-2-deoxyguanosine; p < 0.001).
      Therefore, the elevated levels of nucleosides could be used as an important
      biomarker for breast-cancer research.

PMID- 16799934
TI  - Statistical potential-based amino acid similarity matrices for aligning distantly
      related protein sequences.
AB  - Aligning distantly related protein sequences is a long-standing problem in
      bioinformatics, and a key for successful protein structure prediction. Its
      importance is increasing recently in the context of structural genomics projects
      because more and more experimentally solved structures are available as templates
      for protein structure modeling. Toward this end, recent structure prediction
      methods employ profile-profile alignments, and various ways of aligning two
      profiles have been developed. More fundamentally, a better amino acid similarity
      matrix can improve a profile itself; thereby resulting in more accurate profile
      profile alignments. Here we have developed novel amino acid similarity matrices
      from knowledge-based amino acid contact potentials. Contact potentials are used
      because the contact propensity to the other amino acids would be one of the most
      conserved features of each position of a protein structure. The derived amino
      acid similarity matrices are tested on benchmark alignments at three different
      levels, namely, the family, the superfamily, and the fold level. Compared to
      BLOSUM45 and the other existing matrices, the contact potential-based matrices
      perform comparably in the family level alignments, but clearly outperform in the
      fold level alignments. The contact potential-based matrices perform even better
      when suboptimal alignments are considered. Comparing the matrices themselves with
      each other revealed that the contact potential-based matrices are very different
      from BLOSUM45 and the other matrices, indicating that they are located in a
      different basin in the amino acid similarity matrix space.

PMID- 16799935
TI  - Teratological study of the herbicide 4-chloro-2-methylphenoxyacetic acid in
      rabbits.
AB  - 4-Chloro-2-methylphenoxyacetic acid (MCPA) is an aryloxyacetic acid derivative
      categorised as a plant hormone herbicide. The aim of the study was to evaluate
      the effect of MCPA on pregnant females and the prenatal development of rabbits.
      The substance tested was administered orally to pregnant New Zealand White
      rabbits from day 6 to day 27 of gestation at doses of 5, 10 and 25 mg kg(-1) day(
      1). The animals were killed on day 28 of gestation and live fetuses were examined
      for gross, skeletal and visceral anomalies. Administration of MPCA did not induce
      any signs of maternal toxicity. There was a significant decrease of fetal and
      placental weight compared with controls at the highest dose of MPCA. No adverse
      effect of the substance tested was seen on uterine content variables, e.g.
      corpora lutea, pre-implantation and post-implantation loss, early, late
      resorptions, live and dead fetuses and sex ratio. Rabbit fetuses treated with the
      middle and highest doses of MPCA had a significantly elevated incidence of skull
      and pelvic bone delays. In conclusion, prenatal administration of MCPA did not
      exhibit a teratogenic effect on rabbit fetus development.

PMID- 16799936
TI  - Portal vein thrombosis: evolving techniques to attack this old nemesis.

PMID- 16799937
TI  - Resolution of severe graft steatosis following dual-graft living donor liver
      transplantation.
AB  - Although severely steatotic liver grafts are not suitable for transplantation,
      they have been used when other, more optimal donors were not available,
      especially for living donor liver transplantation (LDLT) using two liver grafts.
      Here we present two cases of dual-graft LDLT in which the recipients showed rapid
      and complete clearing of fat from livers with previously severe steatosis. In the
      first case, two left lateral segment grafts were used, one of which was 70%
      steatotic. Preoperative and posttransplant two-week liver-to-spleen computed
      tomography-value (L/S) ratios were 0.48 and 1.25, respectively. A liver biopsy
      taken two weeks after transplantation showed that the fatty changes had almost
      disappeared. The second case used one left lobe and one left lateral segment
      graft, the latter of which was 80% steatotic. Preoperative and two-week L/S ratio
      were 0.58 and 1.34, respectively, and a liver biopsy taken two weeks after
      transplantation showed less than 3% steatosis. The two donors of the severely
      steatotic liver grafts recovered uneventfully. These findings show that the fat
      content of the liver grafts was rapidly removed after transplantation. This
      observation is helpful in understanding the recovery sequences following
      transplantation of steatotic liver grafts, as well as expanding the acceptability
      of steatotic liver grafts.

PMID- 16799938
TI  - Herpes simplex in a liver transplant recipient.

PMID- 16799939
TI  - The safest way to play domino.

PMID- 16799940
TI  - Management of subcapsular hematoma of the graft after living donor liver
      transplantation.
AB  - Subcapsular hematoma of the graft is a serious complication of liver
      transplantation (LT), and there has been no discussion in the literature about
      optimal management except in sporadic case reports. The aim of this work is to
      review our experience of subcapsular hematoma in living donor liver
      transplantation (LDLT) and to introduce our management strategy. Among the 818
      cases of adult-to-adult LDLT between February 1997 and November 2005, there have
      been 4 cases of subcapsular hematoma. Two of these developed after percutaneous
      liver biopsy and the other 2 developed after percutaneous transhepatic biliary
      drainage (PTBD). Two developed immediately after the procedure, whereas the other
      2 developed 8 and 12 days after the procedure, respectively, due to rupture of a
      pseudoaneurysm. Our management strategy was as follows; after performing dynamic
      computed tomography for initial diagnosis, these 3 steps were taken: 1) hepatic
      arteriography and selective embolization of bleeding focus; 2) pigtail catheter
      drainage (PCD) of subcapsular hematoma; and 3) hepatic vein stenting if there was
      a sign of outflow disturbance due to compression by a large hematoma. All 4 of
      our patients recovered from the insult of subcapsular hematoma. In conclusion,
      our results indicate that patients who develop subcapsular hematoma after LDLT
      can be treated nonsurgically.

PMID- 16799941
TI  - Isolated liver transplantation in infants with short gut syndrome: is less
      better?

PMID- 16799942
TI  - The natural history of hepatitis C virus in pediatric liver transplant
      recipients.
AB  - Although rare in the pediatric population, the natural history of hepatitis C
      virus (HCV) recurrence in pediatric patients undergoing orthotopic liver
      transplantation (OLT) for end-stage liver disease secondary to HCV has not been
      well described. We performed an analysis of all 67 pediatric patients (< 17 years
      old) who have undergone OLT for HCV in the United States between 1/1988 and
      6/2005. The 67 pediatric patients received a total of 83 OLTs for HCV. Following
      initial OLTs performed for HCV, the patient and allograft survival rates were
      71.6% and 55.0%, respectively, at 5 years. Following retransplantation these
      rates decreased to 55.0% and 33.8%, respectively, following retransplantation.
      Recipients were listed for retransplantation after 31.3% of all OLTs, and overall
      recipients were retransplanted after 19.3% of OLTs. The overwhelming majority of
      retransplants were performed for HCV recurrence. A mean of 1.2 OLTs were
      performed per patient for HCV. The median time between OLTs for HCV was 290 days.
      In conclusion, the risk of HCV recurrence in pediatric OLT recipients is high and
      is associated with a high rate of retransplantation. Still, OLT represents the
      only treatment option that may achieve long-term survival in pediatric patients
      with end-stage liver disease secondary to HCV that is recalcitrant to medical
      management.

PMID- 16799944
TI  - Pregnancy after liver transplantation.

PMID- 16799943
TI  - Pregnancy outcome after liver transplantation: a single-center experience of 71
      pregnancies in 45 recipients.
AB  - Infertility is common in women with end-stage liver disease. Successful liver
      transplant (LT), however, can restore childbearing potential. Controversy exists
      regarding the most appropriate immunosuppressive regimen and timing of conception
      following LT. We report the outcomes of a review of all pregnancies occurring
      following LT at King's College Hospital, London, from 1988 to 2004. Seventy-one
      pregnancies were recorded in 45 women. Tacrolimus (60%) and cyclosporin A (38%)
      were the predominant primary immunosuppressive agents used. Median age at
      conception was 29 years (range, 19-42), with a median time from LT to conception
      of 40 months (range, 1-111). There were 50 live births, and no maternal or fetal
      deaths related to pregnancy. There were no graft losses. Median gestation was 37
      weeks (range, 24-42) with a median birth weight of 2,690 g (range, 554-4,260).
      Caesarean section was performed in 40% of pregnancies. Complications included
      pregnancy-induced hypertension in 20%, preeclampsia in 13%, acute cellular
      rejection in 17%, and renal impairment in 11%. There was no statistically
      significant difference in complication rates observed between immunosuppressive
      groups. Pregnancies occurring within 1-year posttransplant had an increased
      incidence of prematurity, low birth weight, and acute cellular rejection compared
      to those occurring later than 1 year. In conclusion, this study confirms that
      favorable outcomes of pregnancy post-LT can be expected for the majority of
      patients. However, delaying pregnancy until after 1-year post-LT is advisable,
      since doing so maybe associated with a lower risk of prematurity.

PMID- 16799945
TI  - Hepatitis C, liver transplantation, and why we should consider children
      separately.

PMID- 16799946
TI  - A systematic review of the performance of the model for end-stage liver disease
      (MELD) in the setting of liver transplantation.
AB  - The Model for End-Stage Liver Disease (MELD) score is now used for allocation in
      liver transplantation (LT) waiting lists, replacing the Child-Turcotte-Pugh (CTP)
      score. However, there is debate as whether it is superior to CTP score to predict
      mortality in patients with cirrhosis on the LT waiting list and after LT. We
      reviewed studies comparing the accuracy of MELD vs. CTP score in transplantation
      settings. We found that in studies of the LT waiting list (12,532 patients with
      cirrhosis), only 4 of 11 showed MELD to be superior to CTP in predicting short
      term (3-month) mortality. In addition, 2 of 3 studies (n = 1,679) evaluating the
      changes in MELD score (DeltaMELD) showed that DeltaMELD had better prediction for
      mortality than the baseline MELD score. The impact of MELD on post-LT mortality
      was assessed in 15 studies (20,456 patients); only 6 (9,522 patients) evaluated
      the discriminative ability of MELD score using the concordance (c) statistic (the
      MELD score had always a c-statistic < 0.70). In 11 studies (19,311 patients),
      high MELD score indicated poor post-LT mortality for cutoff values of 24-40
      points. In re-LT patients, 2 of 4 studies evaluated the discriminative ability of
      MELD score on post-LT mortality. Finally, several studies have shown that the
      predictive ability of MELD score increases by adding clinical variables (hepatic
      encephalopathy, ascites) or laboratory (sodium) parameters. On the basis of the
      current literature, MELD score does not perform better than the CTP score for
      patients with cirrhosis on the waiting list and cannot predict post-LT mortality.

PMID- 16799947
TI  - Portocaval hemitransposition in pediatric liver transplant recipients: a single
      center experience.
AB  - Few studies have reported a series of patients who have undergone portocaval
      hemitransposition at the time of orthotopic liver transplantation (OLT).
      Furthermore, no series report the outcome of pediatric patients who required the
      procedure. This work analyzes the experience with portocaval hemitransposition in
      the pediatric liver transplant population at a single center since the initial
      description of the procedure. We carried out a retrospective analysis of all
      pediatric liver transplants performed in our institution during the 8-year period
      from January 1, 1997, to December 31, 2004. Of 320 pediatric patients who
      received OLT during the study period, 7 underwent portocaval hemitransposition
      (2.2%). Five of the patients had biliary atresia. Four grafts were whole
      cadaveric livers, while the remaining 4 were left lateral segments from either in
      situ cadaveric split (n = 3) or living donation (n = 1). One patient received a
      whole cadaveric allograft and was retransplanted with a segment 2/3 graft; in
      both cases portocaval hemitransposition was utilized. Average warm ischemia time
      was 54 +/- 16 minutes. Three patients had primary nonfunction of the allograft; 2
      were retransplanted with successful outcome, and the remaining patient died
      before retransplantation. Another patient died from recurrent disease. Four of 7
      are long-term survivors and demonstrate good liver function as long as 8 years
      posttransplant. In conclusions, long-term survival is possible following OLT with
      portocaval hemitransposition in pediatric patients. However, rates of primary
      graft nonfunction can be high. Appropriate selection of recipient and type of
      donor graft are essential for good outcomes. Portocaval hemitransposition should
      be used cautiously and as a last resort to establish portovenous inflow.

PMID- 16799948
TI  - Acquired hepatocerebral degeneration in a patient with HCV cirrhosis: complete
      resolution with subsequent recurrence after liver transplantation.
AB  - Acquired (non-Wilsonian) hepatocerebral degeneration (AHD) is a chronic brain
      disorder caused by liver dysfunction and long-standing portal-systemic shunting.
      It typically presents with dysathria, ataxia, tremor, involuntary movements and
      altered mental status, and often does not respond to conventional medical therapy
      for hepatic encephalopathy. There is scarce and conflicting information regarding
      the clinical course of AHD after liver transplantation (OLT). We present a case
      of a 47-year-old woman with hepatitis C (HCV) cirrhosis who developed severe
      manifestations of AHD after multiple bouts of hepatic encephalopathy. Her first
      OLT was complicated with primary nonfunction requiring immediate
      retransplantation. The second OLT led to complete clinical and radiological
      resolution of the AHD. However the patient developed recurrence of AHD 11 months
      post-transplant due to recurrent HCV and chronic rejection leading to cirrhosis
      of the graft. The patient developed severe neurological symptoms, despite mild
      synthetic graft dysfunction. A third OLT led again to disappearance of the
      clinical and radiological manifestations of AHD. AHD may show complete resolution
      after OLT; however it may rapidly recur following recurrent liver disease or
      graft dysfunction.

PMID- 16799950
TI  - Hepatocellular carcinoma in the setting of liver transplantation.

PMID- 16799949
TI  - Hereditary lysozyme amyloidosis: spontaneous hepatic rupture (15 years apart) in
      mother and daughter. role of emergency liver transplantation.
AB  - Hepatic rupture is a rare condition, and treatment options are very limited. We
      report a case of hepatic rupture secondary to hereditary lysozyme amyloidosis
      that was successfully treated by liver transplantation. The mother of this
      patient had presented in an identical fashion 15 years earlier in the
      pretransplant era and died very rapidly.

PMID- 16799952
TI  - Treatment of HCV recurrence: do the pretransplantation rules apply?

PMID- 16799953
TI  - Hematopoietic stem cells mobilized by granulocyte colony-stimulating factor
      partly contribute to liver graft regeneration after partial orthotopic liver
      transplantation.
AB  - On the basis of the recently recognized potential of hematopoietic stem cells
      (HSCs) to give rise to hepatocytes, we investigated whether HSCs mobilized by
      granulocyte colony-stimulating factor (G-CSF) or G-CSF per se could contribute to
      faster recovery and promote tissue reparation after rats' (cross-sex) partial
      orthotopic liver transplantation (PLTx). Sex-mismatched (female to male)
      syngeneic rat PLTx was established. The recipients were repeatedly administrated
      recombinant G-CSF for 5 consecutive days before (G-CSF + PLTx group) and after
      PLTx (PLTx + G-CSF group). Compared with those in PLTx group, CD34+ cells in
      peripheral blood and portal tract region increased from day 1 to 7 after
      transplantation in G-CSF + PLTx group and from day 3 to 14 after transplantation
      in PLTx + G-CSF group, respectively, which suggested that CD34+ HSCs were
      mobilized and migrated into liver graft. Compared with that in G-CSF + PLTx and
      PLTx groups, there was a higher survival rate in the PLTx + G-CSF group. On day 3
      after surgery, the level of aspartate aminotransferase and alanine
      aminotransferase were lower, whereas the mitosis index, proliferating cell
      nuclear antigen-positive nuclei, bromodeoxyuridine (BrdU) incorporation, and
      graft-to-recipient weight ratio were higher in the PLTx + G-CSF group. In
      contrast, these parameters had no significant difference between G-CSF + PLTx and
      PLTx groups. To define the origin of proliferating cells reconstituting liver
      after injury, sry+ (sex-determining region for Y chromosome) and sry+/cytokeratin
      19+ (CK19) cells were quantitated. Higher percentage of sry+ and sry+/CK19+ cells
      in PLTx + G-CSF was detected than in G-CSF + PLTx groups on day 14 after surgery,
      although the liver engraftment rate still remained rather low. Some of the
      sry+/CK19+ cells in the portal tract areas were similar to hepatic oval
      cells/cholangiocytes. In conclusion, G-CSF administration after PLTx greatly
      improved survival rate and liver regeneration of partial graft, partly by its
      mobilizing HSCs into the injured liver to differentiate into hepatocytes through
      hepatic oval cells'/cholangiocytes' engraftment.

PMID- 16799955
TI  - Use of recombinant factor VIIa during orthotopic liver transplantation.

PMID- 16799957
TI  - Anonymous pilot study of hepatitis C virus prevalence in liver transplant
      surgeons.
AB  - The risk of hepatitis C virus (HCV) transmission to surgeons is related to the
      HCV prevalence in the surgical patient population. As HCV-related cirrhosis is
      the commonest indication for liver transplantation in Europe and North America,
      liver transplant surgeons are at particular risk. The prevalence of HCV infection
      in liver transplant surgeons is unknown. The aim of this study was to estimate
      the prevalence of HCV infection in liver transplant surgeons attending the 9th
      Congress of the International Liver Transplantation Society using unlinked
      anonymous testing for HCV. Surgeons attending the conference were invited to
      complete an anonymised questionnaire regarding their surgical and transplant
      practice and provide an unlinked anonymised blood spot sample by finger prick.
      Samples were screened for antibodies to HCV (enzyme-linked immunosorbent assay
      III, Ortho Diagnostics, Raritan, NJ). Polymerase chain reaction testing for HCV
      RNA was performed on reactive samples.A total of 117 liver transplant surgeons
      (79 European, 16 North American, 10 Asian, 9 South American, 3 Australasian)
      provided a blood spot sample. Two (1.7%) surgeons had antibodies to HCV, 1 (0.8%)
      had detectable HCV RNA (genotype 1a). Assuming that both infections were acquired
      during surgery, the estimated maximum rate of HCV transmission is 1 per 743 to
      1,045 years of surgical (0.96 to 1.35 HCV transmissions per 1,000 years of
      general surgical practice) and 449 to 683 years of liver transplant practice
      (1.46 to 2.23 HCV transmissions per 1,000 years of liver transplantation
      practice). In conclusion, risk of HCV transmission to liver transplant surgeons
      appears to be low despite the particular risks associated with frequently
      operating on HCV infected patients.

PMID- 16799958
TI  - Liver transplantation for patients with metastatic endocrine tumors: single
      center experience with 15 patients.
AB  - In contrast to other secondary liver malignancy, orthotopic liver transplantation
      (OLT) is considered as a treatment modality for nonresectable endocrine liver
      metastases in selected patients. However, only few series have assessed patient
      selection criteria and long-term results, and no reports have focused on the
      impact of new technologies in this regard. Between 1992 and 2004, 28 patients
      with malignant endocrine tumors underwent evaluation for OLT according to our
      protocol. Data were entered into a prospective database. During pretransplant
      evaluation, somatostatin receptor scintigraphy detected extrahepatic metastases
      not diagnosed in standard imaging in 10 patients. Of them, 3 showed aberrant Ki67
      labeling results. One patient was excluded from further evaluation due to severe
      carcinoid heart. Thus far, 15 patients, 10 men and 5 women, aged 37 to 67 years,
      were subjected to the transplant procedure (11 deceased donor OLT, 3 living donor
      liver transplantations, and 1 cluster transplantation). Four patients died during
      the hospital treatment. The median follow-up of the discharged patients was 60.8
      months. The actuarial patient survival was 78.3% at 1 year and 67.2% at 5 years.
      The actuarial 1-, 2-, and 5-year tumor-free survival amounted to 69.4%, 48.3%,
      and 48.3%, respectively. Two patients underwent surgery for isolated tumor
      recurrence. In 2 patients, peptide receptor radiotherapy was carried out because
      of multilocular recurrent disease. In conclusion, liver transplantation is a
      realistic therapeutic option for highly selected patients with hepatic metastases
      of endocrine tumors. Our strategy, which implements strict pretransplant
      selection and aggressive surgical approach, in case of disease recurrence, in
      addition to systemic radiopeptide treatment, led to an excellent long-term
      survival cure, however, is unlikely to be achieved.

PMID- 16799959
TI  - Does the Banff rejection activity index predict outcome in patients with early
      acute cellular rejection following liver transplantation?
AB  - The Banff schema incorporates a semiquantitative scoring system for grading of
      acute cellular rejection (ACR) of the liver allograft. The Banff rejection
      activity index (RAI) comprises 3 components scored from 0 to 3: venous
      endothelial inflammation (E); bile duct damage (B); and portal inflammation (P);
      the scores are combined to an overall score (the RAI). The purpose of this
      research was to determine the prognostic value of the Banff RAI score in
      predicting the response to increased immunosuppression and the long-term outcome
      of the graft. A retrospective study was done of patients undergoing primary liver
      transplantation between January 2000 and October 2004 with tacrolimus-based
      immunosuppression; 495 patients were included, 231 had histologically-confirmed
      ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation
      between the total RAI score and response to steroids, resistant rejection,
      development of chronic rejection, or graft survival. The E score was related to
      patient survival, a lower score being associated with a worse outcome (P =
      0.048). In multivariable analysis, serum bilirubin, serum aspartate
      aminotransferase, and E score were significant predictors of death (P = 0.012).
      In univariable analysis, B score and bilirubin were significantly related to
      "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was
      significant in multivariable analysis (logistic regression). In conclusion,
      although the Banff RAI score is a useful marker of the severity of rejection,
      neither the total RAI score nor any of the individual components correlated with
      response to steroids or graft survival.

PMID- 16799960
TI  - TIP30 inhibits growth of HCC cell lines and inhibits HCC xenografts in mice in
      combination with 5-FU.
AB  - Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The
      specific cellular gene alterations responsible for hepatocarcinogenesis are not
      well known. Previous works showed that loss of TIP30, also called CC3, a putative
      tumor suppressor, increased the incidence of hepatocellular carcinoma in mice,
      and some clinical samples of human HCC tissues had aberrant expression of TIP30.
      Here, we report that the introduction of TIP30 by an adenovirus vector into HCC
      cell lines that had decreased expressions of TIP30 inhibited cell proliferation,
      decreased anchorage-dependent growth, suppressed invasion through the
      extracellular matrix, and inhibited tumorigenesis in nude mice. Moreover,
      exogenous expression of Tip30 sensitized HCC cells to cytotoxic drugs and to
      apoptosis induced by tumor necrosis factor-related ligands in vitro. Ectopic
      expression of TIP30 in HCC cells enhanced p53 expression and decreased Bcl-2/Bcl
      xL expression. Treatment of nude mice bearing subcutaneously established HCC
      tumors with a combination of an adenovirus expressing TIP30 and the cytotoxic
      drug 5-fluorouracil completely suppressed tumor growth and prolonged survival. In
      conclusion, TIP30 may play an important role in the suppression of
      hepatocarcinogenesis by acting as a tumor suppressor. Overexpression of TIP30
      might be a promising candidate as a treatment for HCC that would increase
      sensitivity to chemotherapeutic drugs.

PMID- 16799961
TI  - Molecular evolution of 5' flanking regions of 87 candidate genes for
      atherosclerotic cardiovascular disease.
AB  - Inter-individual variation in quantitative traits as well as in disease
      susceptibility may be due to differences in the level and spatio-temporal pattern
      of gene expression. An evolutionary model of genetic variation in cis-regulatory
      regions may help identify loci of interest for the study of the genetic basis of
      complex diseases such as atherosclerotic cardiovascular disease (ASCVD). We
      studied the molecular evolution of 87 candidate genes for ASCVD to detect
      signatures of selection in 5' flanking regions. Resequenced data for these genes
      were available in 24 African-Americans, 23 European-Americans, and 1 chimpanzee
      (Pan troglodytes). Statistical tests of evolutionary neutrality (Tajima's D and
      Fay and Wu's H) were performed using coalescent simulations under a standard
      neutral model and a population structure model to differentiate selection from
      human demographic history. Evidence suggestive of selection was present in 5'
      flanking regions of 15 genes. A modified McDonald-Kreitman test was used to
      compare the ratio of putative functional and non-functional sites between and
      within species in 5' flanking regions. A significant excess or deficit of fixed
      changes over polymorphisms was noted in 16 genes. Of the 26 genes showing
      deviation from evolutionary neutrality based on the above two tests, 13 genes
      showed an unusual haplotype pattern in 5' flanking regions, providing supportive
      evidence of selection. These results indicate that selection may play a role in
      establishing variation in 5' flanking regions of a subset of candidate genes for
      ASCVD and motivate further studies of these loci in determining inter-individual
      susceptibility to ASCVD.

PMID- 16799963
TI  - Different anti-HCV profiles of statins and their potential for combination
      therapy with interferon.
AB  - We recently developed a genome-length hepatitis C virus (HCV) RNA replication
      system (OR6) with luciferase as a reporter. The OR6 assay system has enabled
      prompt and precise quantification of HCV RNA replication. Pegylated interferon
      (IFN) and ribavirin combination therapy is the world standard for chronic
      hepatitis C, but its effectiveness is limited to about 55% of patients. Newer
      therapeutic approaches are needed. In the present study, we used the OR6 assay
      system to evaluate the anti-HCV activity of 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitors, called statins, and their effects in combination
      with IFN-alpha. Five types of statins (atorvastatin, fluvastatin, lovastatin,
      pravastatin, and simvastatin) were examined for their anti-HCV activities.
      Fluvastatin exhibited the strongest anti-HCV activity (IC50: 0.9 micromol/L),
      whereas atorvastatin and simvastatin showed moderate inhibitory effects. However,
      lovastatin, reported recently as an inhibitor of HCV replication, was shown to
      exhibit the weakest anti-HCV activity. The anti-HCV activities of statins were
      reversed by the addition of mevalonate or geranylgeraniol. Surprisingly, however,
      pravastatin exhibited no anti-HCV activity, although it worked as an inhibitor
      for HMG-CoA reductase. The combination of IFN and the statins (except for
      pravastatin) exhibited strong inhibitory effects on HCV RNA replication. In
      combination with IFN, fluvastatin also exhibited a synergistic inhibitory effect.
      In conclusion, statins, especially fluvastatin, could be potentially useful as
      new anti-HCV reagents in combination with IFN.

PMID- 16799964
TI  - The National Commission on Digestive Diseases.

PMID- 16799965
TI  - Nodular regenerative hyperplasia: not all nodules are created equal.

PMID- 16799966
TI  - Extrahepatic replication of HCV: insights into clinical manifestations and
      biological consequences.
AB  - An estimated 170 million persons are infected with the hepatitis C virus (HCV)
      worldwide. While hepatocytes are the major site of infection, a broad clinical
      spectrum of extrahepatic complications and diseases are associated with chronic
      HCV infection, highlighting the involvement of HCV in a variety of non-hepatic
      pathogenic processes. There is a growing body of evidence to suggest that HCV can
      replicate efficiently in extrahepatic tissues and cell types, including
      peripheral blood mononuclear cells. Nonetheless, laboratory confirmation of HCV
      replication in extrahepatic sites is fraught with technical challenges, and in
      vitro systems to investigate extrahepatic replication of HCV are severely
      limited. Thus, future studies of extrahepatic replication should combine
      innovative in vitro assays with a prospective cohort design to maximize our
      understanding of this important phenomenon to the pathogenesis and treatment
      response rates of HCV.

PMID- 16799967
TI  - Favored T helper 1 response in a mouse model of hepatosteatosis is associated
      with enhanced T cell-mediated hepatitis.
AB  - Steatohepatitis enhances the severity of liver injury caused by acute
      inflammation. The purpose of this study was to test the hypothesis that fatty
      liver due to chronic choline-deficient diet exacerbates concanavalin A (ConA)
      induced liver hepatitis, which is predominantly facilitated by T cells. Male
      C57BL/6 mice were fed either control choline-sufficient diet (CSD) or choline
      deficient diet (CDD) for 6 weeks before ConA administration. Mice were sacrificed
      3, 9, and 24 hours after ConA injection. Liver injury measured by aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), pathology, and terminal
      deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining was
      minimal in mice fed either diet before ConA exposure. However, ConA-induced liver
      injury was significantly greater in CDD-fed mice compared with control-fed mice.
      Liver cytokines were assessed by quantitative real-time polymerase chain reaction
      (PCR). The expression of T helper (Th) 1 cytokines tumor necrosis factor alpha
      (TNF-alpha), interleukin 12 (IL-12), and interferon gamma (IFN-gamma) were
      dramatically elevated after ConA in CDD-fed mice compared with control-fed mice.
      CDD also enhanced ConA-induced STAT4 activation, but not STAT6. Notably,
      regulators of T-cell differentiation were strongly shifted toward a predominant
      Th1 profile. T-bet, regulator of the Th1 response, was up-regulated in CDD-fed
      mice, whereas Th2 regulator GATA-3 was significantly suppressed in CDD-fed mice
      after ConA. Moreover, the expression of suppressor of cytokine signaling (SOCS)
      1, SOCS-3, and repressor of GATA-3 (ROG) favored a predominant Th1 cytokine
      response in CDD-fed mice. In conclusion, these data support the hypothesis that
      hepatosteatosis caused by CDD is associated with more severe ConA-induced
      hepatitis due to a predominant shift toward Th1 response.

PMID- 16799968
TI  - Constitutive androstane receptor (CAR) ligand, TCPOBOP, attenuates Fas-induced
      murine liver injury by altering Bcl-2 proteins.
AB  - The constitutive androstane receptor (CAR) modulates xeno- and endobiotic
      hepatotoxicity by regulating detoxification pathways. Whether activation of CAR
      may also protect against liver injury by directly blocking apoptosis is unknown.
      To address this question, CAR wild-type (CAR+/+) and CAR knockout (CAR-/-) mice
      were treated with the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene
      (TCPOBOP) and then with the Fas agonist Jo2 or with concanavalin A (ConA).
      Following the administration of Jo2, hepatocyte apoptosis, liver injury, and
      animal fatalities were abated in TCPOBOP-treated CAR+/+ but not in CAR-/- mice.
      Likewise, acute and chronic ConA-mediated liver injury and fibrosis were also
      reduced in wild-type versus CAR(-/-) TCPOBOP-treated mice. The proapoptotic
      proteins Bak (Bcl-2 antagonistic killer) and Bax (Bcl-2-associated X protein)
      were depleted in livers from TCPOBOP-treated CAR+/+ mice. In contrast, mRNA
      expression of the antiapoptotic effector myeloid cell leukemia factor-1 (Mcl-1)
      was increased fourfold. Mcl-1 promoter activity was increased by transfection
      with CAR and administration of TCPOBOP in hepatoma cells, consistent with a
      direct CAR effect on Mcl-1 transcription. Indeed, site-directed mutagenesis of a
      putative CAR consensus binding sequence on the Mcl-1 promoter decreased Mcl-1
      promoter activity. Mcl-1 transgenic animals demonstrated little to no acute liver
      injury after administration of Jo2, signifying Mcl-1 cytoprotection. In
      conclusion, these observations support a prominent role for CAR cytoprotection
      against Fas-mediated hepatocyte injury via a mechanism involving upregulation of
      Mcl-1 and, likely, downregulation of Bax and Bak.

PMID- 16799969
TI  - Gender, fatty liver and GGT.

PMID- 16799970
TI  - Side population (SP) cells: taking center stage in regeneration and liver cancer?

PMID- 16799971
TI  - Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and
      outcome in acetaminophen-induced acute liver failure.
AB  - Acute liver failure (ALF) shares striking similarities with septic shock where a
      decrease in HLA-DR expression on monocytes is associated with disease severity
      and predicts outcome. We investigated monocyte HLA-DR expression in ALF in
      relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR
      expression was determined in 50 patients with acetaminophen-induced ALF (AALF)
      and 20 non-acetaminophen-induced ALF (NAALF). AALF patients were divided into
      dead/transplanted (AALF-NS, n = 26) and spontaneous survivors (AALF-S, n = 24).
      Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served
      as controls. Monocyte HLA-DR expression was determined by double-color flow
      cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14.
      Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-alpha
      and interferon (IFN)-gamma were concomitantly measured by ELISA. Compared to
      healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was
      lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S,
      AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of
      IL-4, IL-6, IL-10 and TNF-alpha (P < .001). HLA-DR percentage negatively
      correlated with INR, blood lactate, pH and levels of encephalopathy (r = -0.8 to 
      0.5, P < .01), IL-10 (r = -0.8, P < .0001), TNF-alpha (r = -0.4, P = .02). HLA-DR
      percentage level <or=15% has a 96% sensitivity and 100% specificity and 98%
      accuracy in predicting poor prognosis. In conclusion, the strong relationship of
      monocyte HLA-DR expression with indices of disease severity, mediators of
      inflammation and outcome indicates a key role for this molecule as a biomarker of
      disease severity and prognosis.

PMID- 16799972
TI  - Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion
      despite reduced functional capacity.
AB  - Cirrhosis of the liver is frequently accompanied by complex alterations in the
      hemostatic system, resulting in a bleeding tendency. Although many hemostatic
      changes in liver disease promote bleeding, compensatory mechanisms also are
      found, including high levels of the platelet adhesive protein von Willebrand
      Factor (VWF). However, conflicting reports on the functional properties of VWF in
      cirrhosis have appeared in literature. We have measured a panel of VWF parameters
      in plasma from patients with cirrhosis of varying severity and causes.
      Furthermore, we assessed the contribution of VWF to platelet adhesion, by
      measuring the ability of plasma from patients with cirrhosis to support adhesion
      of normal or patient platelets under flow conditions. VWF antigen levels were
      strongly increased in patients with cirrhosis. In contrast, the relative collagen
      binding activity, as well as the relative ristocetin cofactor activity, was
      significantly lower in patients as compared with controls, indicating loss of
      function. Accordingly, patients had a reduced fraction of high-molecular-weight
      VWF multimers. Both strongly elevated and reduced activity and antigen levels of
      the VWF cleaving protease ADAMTS13 were found in individual patients. Adhesion of
      either normal or patient platelets to a collagen surface was substantially
      increased when these platelets were resuspended in plasma of patients with
      cirrhosis, as compared with control plasma. In conclusion, highly elevated levels
      of VWF in patients with cirrhosis contribute to the induction of primary
      hemostasis despite reduced functional properties of the molecule. This phenomenon
      might compensate for defects in platelet number and function in patients with
      cirrhosis.

PMID- 16799973
TI  - An MLCK-dependent window in late G1 controls S phase entry of proliferating
      rodent hepatocytes via ERK-p70S6K pathway.
AB  - We show that MLCK (myosin light chain kinase) plays a key role in cell cycle
      progression of hepatocytes: either chemical inhibitor ML7 or RNA interference led
      to blockade of cyclin D1 expression and DNA replication, providing evidence that
      MLCK regulated S phase entry. Conversely, inhibition of RhoK by specific
      inhibitor Y27632 or RhoK dominant-negative vector did not influence progression
      in late G1 and S phase entry. Inhibition of either MLCK or RhoK did not block
      ERK1/2 phosphorylation, whereas MLCK regulated ERK2-dependent p70S6K activation.
      In addition, DNA synthesis was reduced in hepatocytes treated with p70S6K siRNA,
      demonstrating the key role played by the kinase in S phase entry. Interestingly,
      after the G1/S transition, DNA replication in S phase was no longer dependent on
      MLCK activity. We strengthened this result by ex vivo experiments and evidenced
      an MLCK-dependent window in late G1 phase of regenerating liver after two-thirds
      partial hepatectomy. In conclusion, our results underline an MLCK-dependent
      restriction point in G1/S transition, occurring downstream of ERK2 through the
      regulation of p70S6K activation, and highlighting a new signaling pathway
      critical for hepatocyte proliferation.

PMID- 16799975
TI  - Phenobarbital regulates nuclear expression of HNF-4alpha in mouse and rat
      hepatocytes independent of CAR and PXR.
AB  - Phenobarbital is a lipophilic molecule used as a sedative and antiepileptic drug
      that elicits a multitude of effects in the liver, including gross liver
      enlargement, hepatocyte hypertrophy, and induced expression of drug-metabolizing
      enzymes and other liver-specific genes. The constitutive androstane receptor
      (CAR; NR1I3) and to a lesser extent the pregnane X receptor (PXR; NR1I2) are
      responsible for mediating induction of many phenobarbital-responsive genes.
      However, CAR-mediated transcriptional control of some genes is critically
      dependent on hepatocyte nuclear factor 4 alpha (HNF-4alpha; NR2A1), which itself
      regulates multiple liver-specific genes involved in hepatic growth, metabolism,
      and differentiation. We studied the effects of phenobarbital on HNF-4alpha
      expression in hepatocytes and provide evidence that HNF-4alpha nuclear expression
      is regulated in response to phenobarbital. Real-time polymerase chain reaction
      analyses revealed that HNF-4alpha mRNA is modestly up-regulated by phenobarbital.
      In addition, nuclear expression of HNF-4alpha protein is significantly elevated 3
      hours after the administration of phenobarbital in wild-type, CAR-/-, and CAR-/
      /PXR-/- mice. In vitro analysis revealed that phenobarbital-induced HNF-4alpha
      expression is both time- and dose dependent. In addition, the phosphatase
      inhibitor okadaic acid and the Ca2+/calmodulin-dependent protein kinase II
      inhibitor KN62 block nuclear induction of HNF-4alpha by phenobarbital.
      Furthermore, HNF-4alpha nuclear expression is enhanced by inhibition of cyclic
      AMP-dependent protein kinase A. In conclusion, induced nuclear expression of HNF
      4alpha and CAR is an integral part of the phenobarbital response, aimed at
      coordinated regulation of genes involved in drug metabolism and detoxification as
      well as maintenance of liver function.

PMID- 16799977
TI  - Side population purified from hepatocellular carcinoma cells harbors cancer stem
      cell-like properties.
AB  - Recent advances in stem cell biology enable us to identify cancer stem cells in
      solid tumors as well as putative stem cells in normal solid organs. In this
      study, we applied side population (SP) cell analysis and sorting to established
      hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function
      as cancer stem cells and to elucidate their roles in tumorigenesis. Among four
      cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells
      (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high
      proliferative potential and anti-apoptotic properties compared with those of non
      SP cells. Immunocytochemistry examination showed that SP fractions contain a
      large number of cells presenting characteristics of both hepatocyte and
      cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency
      (NOD/SCID) xenograft transplant experiments showed that only 1 x 10(3) SP cells
      were sufficient for tumor formation, whereas an injection of 1 x 10(6) non-SP
      cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that
      SP cells generated both SP and non-SP cells and tumor-initiating potential was
      maintained only in SP cells in serial transplantation. Microarray analysis
      discriminated a differential gene expression profile between SP and non-SP cells,
      and several so-called "stemness genes" were upregulated in SP cells in HCC cells.
      In conclusion, we propose that a minority population, detected as SP cells in HCC
      cells, possess extreme tumorigenic potential and provide heterogeneity to the
      cancer stem cell system characterized by distinct hierarchy.

PMID- 16799978
TI  - Biliary drainage transiently relieves intractable pruritus in primary biliary
      cirrhosis.

PMID- 16799979
TI  - In vivo assessment of liver cell apoptosis as a novel biomarker of disease
      severity in nonalcoholic fatty liver disease.
AB  - In patients with nonalcoholic fatty liver disease (NAFLD), a liver biopsy remains
      the only reliable way to differentiate simple steatosis from nonalcoholic
      steatohepatitis (NASH). Noninvasive methods are urgently needed. Increasing
      evidence suggests hepatocyte apoptosis is a key mediator of liver injury in
      NAFLD. The aim of this study was to quantify hepatocyte apoptosis in plasma from
      patients with NAFLD and correlate it with histological severity. Plasma was
      obtained from 44 consecutive patients with suspected NAFLD at the time of liver
      biopsy. Histology was assessed blindly. Caspase-3-generated cytokeratin-18
      fragments were measured in situ via immunohistochemistry and in vivo using a
      novel enzyme-linked immunosorbent assay. Plasma cytokeratin-18 fragments were
      markedly increased in patients with NASH compared with patients with simple
      steatosis or normal biopsies (median [interquartile range]: 765.7 U/L [479.6
      991.1], 202.4 U/L [160.4-258.2], 215.5 U/L [150.2-296.2], respectively; P <
      .001). Cytokeratin-18 fragment levels independently predicted NASH (OR 1.95; 95%
      CI 1.18-3.22; P = .009 for every 50 U/L increase). A cutoff value of 395 U/L
      calculated using the receiver operating characteristic curve approach showed a
      specificity of 99.9%, a sensitivity of 85.7%, and positive and negative
      predictive values of 99.9% and 85.7%, respectively, for the diagnosis of NASH. In
      conclusion, these findings strongly suggest that determination of hepatocyte
      caspase activation in the blood is a strong and independent predictor of NASH in
      human subjects. These data highlight the potential usefulness of this test as a
      noninvasive diagnostic means of determining histological disease severity in
      patients with NAFLD.

PMID- 16799980
TI  - Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to
      hydrophobic bile salts and impairs bile salt transport.
AB  - Progressive familial intrahepatic cholestasis type 1 (PFIC1, Byler disease, OMIM
      211600) is a severe inherited liver disease caused by mutations in ATP8B1. ATP8B1
      is a member of the type 4 subfamily of P-type ATPases, which are phospholipid
      flippases. PFIC1 patients generally develop end-stage liver disease before the
      second decade of life. The disease is characterized by impaired biliary bile salt
      excretion, but the mechanism whereby impaired ATP8B1 function results in
      cholestasis is unclear. In a mouse model for PFIC1, we observed decreased
      resistance of the hepatocanalicular membrane to hydrophobic bile salts as
      evidenced by enhanced biliary recovery of phosphatidylserine, cholesterol, and
      ectoenzymes. In liver specimens from PFIC1 patients, but not in those from
      control subjects, ectoenzyme expression at the canalicular membrane was markedly
      deficient. In isolated mouse livers Atp8b1 deficiency impaired the transport of
      hydrophobic bile salts into bile. In conclusion, our study shows that Atp8b1
      deficiency causes loss of canalicular phospholipid membrane asymmetry that in
      turn renders the canalicular membrane less resistant toward hydrophobic bile
      salts. The loss of phospholipid asymmetry may subsequently impair bile salt
      transport and cause cholestasis.

PMID- 16799981
TI  - Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of
      a Monte Carlo versus partial least squares analysis based feature extraction
      technique.
AB  - BACKGROUND AND OBJECTIVE: We explored the use of diffuse reflectance spectroscopy
      in the ultraviolet-visible (UV-VIS) spectrum for the diagnosis of breast cancer.
      A physical model (Monte Carlo inverse model) and an empirical model (partial
      least squares analysis) based approach, were compared for extracting diagnostic
      features from the diffuse reflectance spectra. STUDY DESIGN/METHODS: The physical
      model and the empirical model were employed to extract features from diffuse
      reflectance spectra measured from freshly excised breast tissues. A subset of
      extracted features obtained using each method showed statistically significant
      differences between malignant and non-malignant breast tissues. These features
      were separately input to a support vector machine (SVM) algorithm to classify
      each tissue sample as malignant or non-malignant. RESULTS AND CONCLUSIONS: The
      features extracted from the Monte Carlo based analysis were hemoglobin
      saturation, total hemoglobin concentration, beta-carotene concentration and the
      mean (wavelength averaged) reduced scattering coefficient. Beta-carotene
      concentration was positively correlated and the mean reduced scattering
      coefficient was negatively correlated with percent adipose tissue content in
      normal breast tissues. In addition, there was a statistically significant
      decrease in the beta-carotene concentration and hemoglobin saturation, and a
      statistically significant increase in the mean reduced scattering coefficient in
      malignant tissues compared to non-malignant tissues. The features extracted from
      the partial least squares analysis were a set of principal components. A subset
      of principal components showed that the diffuse reflectance spectra of malignant
      breast tissues displayed an increased intensity over wavelength range of 440-510
      nm and a decreased intensity over wavelength range of 510-600 nm, relative to
      that of non-malignant breast tissues. The diagnostic performance of the
      classification algorithms based on both feature extraction techniques yielded
      similar sensitivities and specificities of approximately 80% for discriminating
      between malignant and non-malignant breast tissues. While both methods yielded
      similar classification accuracies, the model based approach provided insight into
      the physiological and structural features that discriminate between malignant and
      non-malignant breast tissues.

PMID- 16799982
TI  - Magnetic resonance imaging correlated with the histopathological effect of Pd
      bacteriopheophorbide (Tookad) photodynamic therapy on the normal canine prostate
      gland.
AB  - BACKGROUND AND OBJECTIVE: To determine the optimal magnetic resonance imaging
      (MRI) methodology to assess photodynamic therapy (PDT)-induced histopathological
      responses in the prostate. STUDY DESIGN/MATERIALS AND METHODS: Laparotomy was
      performed in five healthy dogs. Cylindrical diffuser was placed in the prostates
      to deliver light of 50-300 J/cm at 150 mW/cm and 763 nm to activate IV-injected
      Tookad (1 mg/kg b.w.). Fast spin echo (FSE) T2-weighted, post-contrast-enhanced
      T1-(CE-T1) and diffusion weighted images (DWI) were obtained pre- and 2 days, 7
      days, and 1 month post-PDT. Radiological-histopathological correlation was
      performed at 7 days (n = 4) and 1 month (n = 1) after PDT. A qualitative
      assessment of signal changes and apparent diffusion coefficient (ADC) mapping was
      performed. RESULTS: At 2 or 7 days post-PDT, there was good spatial correlation
      between PDT-induced hemorrhagic necrosis and unenhanced regions on CE-T1 images.
      There was a rapidly and persistently enhancing rim corresponding to edema and
      inflammation. FSE T2 and DWI showed altered signal but did not clearly define
      necrosis in all cases. At 1 month, it was hard to correlate MR images to
      histopathologic changes as they represented a mixture of necrosis and developing
      fibrosis, which led to a mixed signal intensity and less demarcated contrast
      enhancement. CONCLUSIONS: At 7 days after PDT, gadolinium DTPA contrast-enhanced
      MRI is superior to DWI and T2 imaging in assessing the boundary of Tookad PDT
      induced tissue necrosis in the normal canine prostate.

PMID- 16799983
TI  - A double-blind randomized trial of adefovir dipivoxil in Chinese subjects with
      HBeAg-positive chronic hepatitis B.
AB  - Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)
      positive chronic hepatitis B (CHB) were enrolled in a multicenter, double-blind,
      randomized, placebo-controlled study of adefovir dipivoxil (ADV) 10 mg once
      daily. There was a significant difference in reduction of serum hepatitis B virus
      (HBV) DNA after 12 weeks between subjects who received ADV and those who received
      the placebo (3.4 and 0.1 log10 copies/mL, respectively, P < .001). Further
      reductions in serum HBV DNA and increases in the proportion of subjects with an
      HBV DNA level of at most 10(5) copies/mL, with HBV DNA undetectable, and with ALT
      normalization were observed in ADV-treated subjects at week 52 (median HBV DNA
      reduction of 4.5 log(10) copies/mL, 67% with HBV DNA <or= 10(5) copies/mL, 28%
      with HBV DNA undetectable, and 79% with ALT normalization). Subjects who
      initially received ADV lost some treatment benefit after being rerandomized to
      the placebo in week 40. Subjects with YMDD mutant HBV at baseline had
      virological, biochemical, and serological responses to treatment that were
      similar to those of subjects with wild-type HBV. The incidence of clinically
      adverse events was similar in nature and severity between the treatment groups,
      and there was no evidence of renal toxicity. No adefovir-related HBV mutations
      were identified. In conclusion, treatment with ADV 10 mg daily over 52 weeks was
      safe and effective in Chinese subjects with HBeAg-positive CHB and did not lead
      to the emergence of drug resistance. The study is continuing for an additional 4
      years with all subjects on open-label ADV 10 mg daily.

PMID- 16799984
TI  - Enhancement by pyrazole of lipopolysaccharide-induced liver injury in mice: role
      of cytochrome P450 2E1 and 2A5.
AB  - The mechanisms by which alcohol causes liver injury are still not certain. Either
      LPS or CYP2E1 are considered independent risk factors involved in alcoholic liver
      disease, but mutual relationships or interactions between them are unknown. In
      the present study, the possible synergistic action of CYP2E1 and LPS in liver
      injury was investigated by evaluating the effects of pyrazole (inducer of
      CYP2E1), Chlormethiazole (CMZ), an inhibitor of CYP2E1, and CYP2E1-knockout mice.
      Mice were injected with pyrazole (150 mg/kg, ip) daily for 2 days, followed by
      LPS injection (4 mg/kg, ip). CMZ (50mg/kg, ip) was administered 15 h before and
      30 min after LPS treatment, respectively. LPS-induced liver injury was enhanced
      by pyrazole, as indicated by pathological changes and increases in ALT and AST,
      and positive TUNEL staining. LPS-induced oxidative stress was also enhanced by
      pyrazole as indicated by increases in 4-hydroxy-2-nonenal and 3-nitrotyrosine
      adduct formation. CMZ protected against the pyrazole enhanced LPS liver injury
      and oxidative stress. CYP2E1 but also CYP2A5 were increased by the pyrazole/LPS
      treatment. CMZ decreased the elevated CYP2E1 activity by 90%, but CYP2A5 activity
      was also lowered (30%-50%). CYP2E1-knockout mice exhibited only minor liver
      injury after treatment with pyrazole/LPS, but wild-type mice exhibited severe
      liver injury. While no CYP2E1 was present in the CYP2E1 knockout mice, CYP2A5
      activity was also lower. In conclusion, induction of CYP2E1 plays an important
      role in the enhancement of LPS liver injury by pyrazole, but some contribution by
      CYP2A5 cannot be excluded.

PMID- 16799985
TI  - The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers
      of rats with CCl4 cirrhosis.
AB  - In cirrhosis, intrahepatic endothelial dysfunction is one of the mechanisms
      involved in the increased resistance to portal blood flow and therefore in the
      development of portal hypertension. Endothelial nitric oxide synthase (eNOS)
      uncoupling due to deficiency of tetrahydrobiopterin (BH4) results in decreased
      production of NO and plays a major role in endothelial dysfunction in other
      conditions. We examined whether eNOS uncoupling is involved in the pathogenesis
      of endothelial dysfunction of livers with cirrhosis. Basal levels of
      tetrahydrobiopterin and guanosine triphosphate (GTP)-cyclohydrolase (BH4 rate
      limiting enzyme) expression and activity were determined in liver homogenates of
      control and rats with CCl4 cirrhosis. Thereafter, rats were treated with
      tetrahydrobiopterin, and eNOS activity, NO bioavailability, assessed with a
      functional assay, and the vasodilator response to acetylcholine (endothelial
      function) were evaluated. Livers with cirrhosis showed reduced BH4 levels and
      decreased GTP-cyclohydrolase activity and expression, which were associated with
      impaired vasorelaxation to acetylcholine. Tetrahydrobiopterin supplementation
      increased BH4 hepatic levels and eNOS activity and significantly improved the
      vasodilator response to acetylcholine in rats with cirrhosis. In conclusion, the
      impaired response to acetylcholine of livers with cirrhosis is modulated by a
      reduced availability of the eNOS cofactor, tetrahydrobiopterin.
      Tetrahydrobiopterin supplementation improved the endothelial dysfunction of
      cirrhotic livers.

PMID- 16799986
TI  - Management of patients with biliary atresia in France: results of a decentralized
      policy 1986-2002.
AB  - This study analyzed the results of the decentralized management of biliary
      atresia (BA) in France, where an improved collaboration between centers has been
      promoted since 1997. Results were compared to those obtained in England and
      Wales, where BA patients have been centralized in three designated centers since
      1999. According to their birth dates, BA patients were divided into two cohorts:
      cohort A, with patients born between 1986 and 1996, had 472 patients; and cohort
      B, with patients born between 1997 and 2002, had 271 patients. Survival rates
      were calculated according to the Kaplan-Meier method and compared by using the
      log rank test and the Cox model. Four-year overall BA patient survival was 73.6%
      (95% CI 69.5%-77.7%) and 87.1% (CI 82.6%-91.6%) in cohorts A and B, respectively
      (P < .001). Median age at time of the Kasai operation was 61 and 57 days in
      cohorts A and B, respectively (NS). Four-year survival with native liver after
      the Kasai operation was 40.1% and 42.7% in cohorts A and B, respectively (NS):
      33.9% (cohort A) and 33.4% (cohort B) in the centers with two or fewer caseloads
      a year, 30.9% (cohort A) and 44.5% (cohort B) in the centers with 3-5 cases/year,
      47.8% (cohort A) and 47.7% (cohort B) in the center with more than 20 caseloads a
      year. In cohorts A and B, 74 (15.7%) and 19 (7%) patients, respectively, died
      without liver transplantation (LT). Four-year survival after LT was 75.1% and
      88.8% in cohorts A and B, respectively (P = .006). In conclusion, BA patients
      currently have the same chance of survival in France as in England and Wales. The
      early success rate of the Kasai operation remains inferior in the centers with
      limited caseloads in France, leading to a greater need for LTs in infancy and
      early childhood.

PMID- 16799987
TI  - Hepatitis B virus genotype G monoinfection and its transmission by blood
      components.
AB  - An acute hepatitis B virus (HBV) infection was diagnosed in a regular apheresis
      (plasma/platelet) donor by the hepatitis B surface antigen (HBsAg) assay and
      minipool nucleic acid amplification technology (NAT). The acute infection was
      confirmed by detection of anti-HBc (IgM) and anti-HBs 2 weeks later. The donor
      showed no clinical symptoms and had normal alanine aminotransferase levels. He
      had a history of weekly apheresis plasma or platelet donations. Archived material
      from the donor and the respective recipients was investigated by sensitive HBV
      NATs as part of a look-back procedure. HBV DNA was detectable in previous
      donations as well as in two recipients transfused with platelet concentrates. The
      rare HBV genotype G was identified in all HBV-DNA-positive samples. Strong
      evidence of genotype G monoinfection was obtained by clonal sequencing, HBV
      genotype line probe assay, genotype-specific NATs, and restriction pattern
      analysis. In contrast to previously described genotype G infections, which all
      appeared as coinfections with genotype A, neither the hepatitis B e antigen
      (HBeAg) nor anti-HBe was detectable in any of the samples. This shows that HBeAg
      is dispensable for viral replication. The delay in detecting HBsAg in both the
      donor and recipient samples may be explained by either decreased genotype G
      specific synthesis of incomplete viral forms in early HBV infection or the lower
      sensitivity to genotype G of the current HBsAg assays. In conclusion, this
      reported case of an HBV infection was caused exclusively by genotype G.

PMID- 16799988
TI  - Supporting the NIH before it is too late.

PMID- 16799989
TI  - Outcome of acute hepatitis C is related to virus-specific CD4 function and
      maturation of antiviral memory CD8 responses.
AB  - A timely, efficient, and coordinated activation of both CD4 and CD8 T cell
      subsets following HCV infection is believed to be essential for HCV control.
      However, to what extent a failure of the individual T cell subsets can contribute
      to the high propensity of HCV to persist is still largely undefined. To address
      this issue, we analyzed the breadth, vigor, and quality of CD4 and CD8 responses
      simultaneously with panels of peptides covering the entire HCV sequence or
      containing the HLA-A2-binding motif, and with recombinant HCV proteins in 16
      patients with acute HCV infection by tetramer staining, ELISPOT, and
      intracellular cytokine staining for interferon gamma, interleukin (IL)-2, IL-4,
      and IL-10. Our results indicate that at clinical onset, CD8 responses are
      similarly weak and narrowly focused in both self-limited and chronically evolving
      infections. At this stage, CD4 responses are deeply impaired in patients with a
      chronic outcome as they are weak and of narrow specificity, unlike the strong,
      broad and T helper 1-oriented CD4 responses associated with resolving infections.
      Only patients able to finally control infection show maturation of CD8 memory
      sustained by progressive expansion of CD127+ CD8 cells. Thus, a poor CD8 response
      in the acute stage of infection may enhance the overall probability of chronic
      viral persistence. In conclusion, the presence of functional CD4 responses
      represents one of the factors dictating the fate of infection by directly
      contributing to control of the virus and by promoting maturation of protective
      memory CD8 responses.

PMID- 16799990
TI  - Actin organization and hepatocyte differentiation are regulated by extracellular
      matrix via PI-4,5-bisphosphate in the rat.
AB  - Cell adhesion to the extracellular matrix (ECM) plays vital roles in both
      morphogenesis and regulation of gene expression in cells of adult organisms. How
      intracellular, cytoskeletal, and signaling factors connect and communicate with
      the ECM is a fundamental question. Using a cDNA microarray analysis, we
      identified phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) phosphatase mRNA as
      being up-regulated in hepatocytes cultured on a basement membrane matrix,
      Engelbreth-Holm-Swarm (EHS) gel, which led to the finding that the PI(4,5)P2
      levels of hepatocytes decreased on EHS gel. These changes in hepatocytes on EHS
      gel were accompanied by promotion of actin depolymerization and differentiated
      phenotypes of the hepatocytes. Treatment with PI(4,5)P2 or a phospholipase C
      inhibitor, U73122, resulted in decreased mRNA expressions of albumin and
      hepatocyte nuclear factor 4 (HNF-4) in hepatocytes. In contrast, actin-disrupting
      agent gelsolin increased mRNA expressions of albumin and HNF-4. In conclusion,
      organization of the actin cytoskeleton via PI(4,5)P2 is involved in the
      regulation of hepatocyte differentiation by the ECM.

PMID- 16799991
TI  - Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell
      cycle status of hepatocytes in vivo.
AB  - Cyclin E1 controls G1/S phase transition of the eukaryotic cell cycle. We report
      the impact of alternative spliced cyclin E1 isoforms on cell cycle regulation in
      hepatocytes. We show that expression of new cyclin E1 mRNA variants IN3, Delta4,
      and Delta5 is associated with retarded proliferation in murine hepatocellular
      carcinoma. Additionally, we demonstrate that a new cyclin E1 isoform Delta3/8
      lacking the central part of wild-type mRNA is expressed predominantly in
      nonproliferating murine hepatocytes. Following partial hepatectomy, Delta3/8 is
      downregulated when hepatocytes enter the cell cycle from quiescence. The Delta3/8
      protein does not exhibit any cyclin box motif but binds cyclin-dependent kinase 2
      without stimulating kinase activity. We demonstrate that Delta3/8 lacks any
      nuclear localization signal and is exclusively located in the cytoplasm.
      Overexpression of Delta3/8 in cultured cells leads to a delayed G0-G1 transition,
      indicating that this splice variant helps to maintain a quiescent state of
      hepatocytes. In conclusion, we identified an isoform of cyclin E1 involved in G0
      maintenance and suggest an additional mechanism for cell cycle control.

PMID- 16799992
TI  - Multiple polymorphic loci determine basal hepatic and splenic iron status in
      mice.
AB  - Polymorphisms of genes linked to iron metabolism may account for individual
      variability in hemochromatosis and iron status connected with liver and
      cardiovascular diseases, cancers, toxicity, and infection. Mouse strains exhibit
      marked differences in levels of non-heme iron, with C57BL/6J and SWR showing low
      and high levels, respectively. The genetic basis for this variability was
      examined using quantitative trait loci (QTL) analysis together with expression
      profiling and chromosomal positions of known iron-related genes. Non-heme iron
      levels in liver and spleen of C57BL/6J x SWR F2 mice were poorly correlated,
      indicating independent regulation. Highly significant (P < .01) polymorphic loci
      were found on chromosomes 2 and 16 for liver and on chromosomes 8 and 9 for
      spleen. With sex as a covariate, additional significant or suggestive (P < 0.1)
      QTL were detected on chromosomes 7, 8, 11, and 19 for liver and on chromosome 2
      for spleen. A gene array showed no clear association between most loci and
      differential iron-related gene expression. The gene for transferrin and a
      transferrin-like gene map close to the QTL on chromosome 9. Transferrin
      saturation was significantly lower in C57BL/6J mice than in SWR mice, but there
      was no significant difference in the serum level of transferrin, hepatic
      expression, or functional change in cDNA sequence. beta2-Microglobulin, which,
      unlike other loci, was associated with C57BL/6J alleles, is a candidate for the
      chromosome 2 QTL for higher iron. In conclusion, the findings show the location
      of polymorphic genes that determine basal iron status in wild-type mice. Human
      equivalents may be pertinent in predisposition to hepatic and other disorders.

PMID- 16799993
TI  - Induction of Gas6 protein in CCl4-induced rat liver injury and anti-apoptotic
      effect on hepatic stellate cells.
AB  - The protein product of the growth arrest-specific gene 6 (Gas6) is a secreted
      ligand for tyrosine kinase receptors, among which Axl is the most widely
      distributed and displays the highest affinity for Gas6. The Gas6/Axl signaling
      pathway has been increasingly implicated in growth and survival processes
      occurring during development and tissue repair. In liver, after an acute or
      chronic injury, repair involves macrophages and hepatic stellate cells (HSC)
      activated into myofibroblastic cells (HSC/MFB), which produce cytokines and
      matrix proteins. We investigated the expression and the role of Gas6 and its
      receptor Axl in liver repair. Three days after CCl4-induced liver injury in the
      rat, we detected the expression of Gas6 in ED1-positive macrophages as well as in
      desmin-positive HSC, which accumulated in injured areas. Axl, the high-affinity
      receptor for Gas6, was detected in macrophages, HSC, and HSC/MFB. In vitro,
      expression of gamma-carboxylated Gas6 was strongly induced in HSC along with
      their transformation into myofibroblasts, and it exerted an anti-apoptotic effect
      on both HSC and HSC/MFB mediated by the Axl/PI3-kinase/Akt pathway. In
      conclusion, Gas6 is a survival factor for these cells and we suggest that Gas6,
      secreted by macrophages and HSC/MFB in vivo after liver injury, promotes HSC and
      HSC/MFB survival and might support transient HSC/MFB accumulation during liver
      healing.

PMID- 16799994
TI  - Lack of assessment of body temperature in mice with acetaminophen toxicity.

PMID- 16799996
TI  - Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter
      expression in human liver.
AB  - Interindividual variability in hepatic canalicular transporter expression might
      predispose to the development of hepatic disorders such as acquired forms of
      intrahepatic cholestasis. We therefore investigated expression patterns of bile
      salt export pump (BSEP, ABCB11), multidrug resistance protein 3 (MDR3, ABCB4),
      multidrug resistance associated protein 2 (MRP2, ABCC2) and multidrug resistance
      protein 1 (MDR1, ABCB1) in healthy liver tissue of a white population. Protein
      expression levels were correlated with specific single nucleotide polymorphisms
      (SNPs) in the corresponding transporter genes. Hepatic protein expression levels
      from 110 individuals undergoing liver resection were assessed by Western blot
      analysis of liver plasma membranes enriched in canalicular marker enzymes. Each
      individual was genotyped for the following synonymous (s) and nonsynonymous (ns)
      SNPs: ABCB11: (ns:1457T>C and 2155A>G), ABCB4: (ns:3826A>G) and ABCC2
      (ns:1286G>A,3600T>A and 4581G>A) and ABCB1 (ns:2677G>T/A and s:3435C>T).
      Transporter expression followed unimodal distribution. However, of all tested
      individuals 30% exhibited a high expression and 32% a low or very low expression
      phenotype for at least one of the four investigated transport proteins.
      Transporter expression levels did not correlate with age, sex, underlying liver
      disease, or presurgery medication. However, low BSEP expression was associated
      with the 1457C-allele in ABCB11 (P = .167) and high MRP2 expression was
      significantly correlated with the 3600A and 4581A ABCC2 variants (P = .006). In
      conclusion, the results demonstrate a considerable interindividual variability of
      canalicular transporter expression in normal liver. Furthermore, data suggest a
      polymorphic transporter expression pattern, which might constitute a risk factor
      for the development of acquired forms of cholestatic liver diseases.

PMID- 16799997
TI  - Development of autoimmune hepatitis in patients with typical primary biliary
      cirrhosis.
AB  - Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is a
      clinical entity characterized by the occurrence of both conditions at the same
      time in the same patient. In addition to PBC-AIH overlap syndrome, transitions
      from one autoimmune disease to another have been reported, but no systematic
      series have been published. We report a series of 12 patients with consecutive
      occurrence of PBC and AIH (i.e., PBC followed by AIH). Among 282 PBC patients, 39
      were identified who fulfilled criteria for probable or definitive AIH. AIH
      developed in 12 patients (4.3%). The baseline characteristics of the patients
      were similar to those of patients with classical PBC. Time elapsed between the
      diagnosis of PBC and the diagnosis of AIH varied from 6 months to 13 years.
      Patients with multiple flares of hepatitis at the time of diagnosis of AIH had
      cirrhosis on liver biopsy. Ten patients were given prednisone +/- azathioprine;
      short-term as well as sustained remissions were obtained in 8 of these, while two
      had multiple relapses and eventually died 8 and 7 years after diagnosis of AIH.
      In conclusion, the development of superimposed AIH could not be predicted from
      baseline characteristics and initial response to UDCA therapy. If not detected
      early, superimposed AIH can result in rapid progression toward cirrhosis and
      liver failure in PBC patients.

PMID- 16799998
TI  - Effects of low-level laser therapy (LLLT) on the nuclear factor (NF)-kappaB
      signaling pathway in traumatized muscle.
AB  - BACKGROUND AND OBJECTIVE: To investigate the effects of low-level laser therapy
      (LLLT) on nuclear factor kappa B (NF-kappaB) activation and inducible nitric
      oxide synthase (iNOS) expression in an experimental model of muscle trauma. STUDY
      DESIGN/MATERIALS AND METHODS: Injury to the gastrocnemius muscle in the rat was
      produced by a single impact blunt trauma. A low-level galium arsenide (Ga-As)
      laser (904 nm, 45 mW, and 5 J/cm2) was applied for 35 seconds duration,
      continuously. RESULTS: Histological abnormalities with increase in collagen
      concentration, and oxidative stress were observed after trauma. This was
      accompanied by activation of NF-kappaB and upregulation of iNOS expression,
      whereas protein concentration of I kappa B alpha decreased. These effects were
      blocked by LLLT. CONCLUSION: LLLT reduced the inflammatory response induced by
      trauma and was able to block the effects of reactive oxygen species (ROS) release
      and the activation of NF-kappaB. The associated reduction of iNOS overexpression
      and collagen production suggest that the NF-kappaB pathway may be a signaling
      route involved in the pathogenesis of muscle trauma.

PMID- 16799999
TI  - Correction of ear malformations by laser-assisted cartilage reshaping (LACR).

PMID- 16800000
TI  - Stratified false discovery control for large-scale hypothesis testing with
      application to genome-wide association studies.
AB  - The multiplicity problem has become increasingly important in genetic studies as
      the capacity for high-throughput genotyping has increased. The control of False
      Discovery Rate (FDR) (Benjamini and Hochberg. [1995] J. R. Stat. Soc. Ser. B
      57:289-300) has been adopted to address the problems of false positive control
      and low power inherent in high-volume genome-wide linkage and association
      studies. In many genetic studies, there is often a natural stratification of the
      m hypotheses to be tested. Given the FDR framework and the presence of such
      stratification, we investigate the performance of a stratified false discovery
      control approach (i.e. control or estimate FDR separately for each stratum) and
      compare it to the aggregated method (i.e. consider all hypotheses in a single
      stratum). Under the fixed rejection region framework (i.e. reject all hypotheses
      with unadjusted p-values less than a pre-specified level and then estimate FDR),
      we demonstrate that the aggregated FDR is a weighted average of the stratum
      specific FDRs. Under the fixed FDR framework (i.e. reject as many hypotheses as
      possible and meanwhile control FDR at a pre-specified level), we specify a
      condition necessary for the expected total number of true positives under the
      stratified FDR method to be equal to or greater than that obtained from the
      aggregated FDR method. Application to a recent Genome-Wide Association (GWA)
      study by Maraganore et al. ([2005] Am. J. Hum. Genet. 77:685-693) illustrates the
      potential advantages of control or estimation of FDR by stratum. Our analyses
      also show that controlling FDR at a low rate, e.g. 5% or 10%, may not be feasible
      for some GWA studies.

PMID- 16800001
TI  - Modulations of VEGF and iNOS in the rat heart by low level laser therapy are
      associated with cardioprotection and enhanced angiogenesis.
AB  - BACKGROUND AND OBJECTIVES: It has been shown previously that low-level laser
      therapy (LLLT) significantly reduces infarct size following induction of
      myocardial infarction in rats and dogs. The aim of the present study was to
      investigate the effect of LLLT on the expression of vascular endothelial growth
      factor (VEGF) and inducible nitric oxide synthase (iNOS). STUDY DESIGN AND
      MATERIAL AND METHODS: Myocardial infarction was induced by occlusion of the left
      descending artery in 87 rats. LLLT was applied to intact and post-infarction.
      VEGF, iNOS, and angiogenesis were determined. RESULTS: Both the laser-irradiated
      rat hearts post-infarction and intact hearts demonstrated a significant increase
      in VEGF and iNOS expression compared to non-laser-irradiated hearts. LLLT also
      caused a significant elevation in angiogenesis. CONCLUSIONS: It is concluded that
      VEGF and iNOS expression in the infarcted rat heart is markedly upregulated by
      LLLT and is associated with enhanced angiogenesis and cardioprotection.

PMID- 16800002
TI  - MTHFR C677T polymorphism and migraine with aura.

PMID- 16800003
TI  - Requirement of reversible caldesmon phosphorylation at P21-activated kinase
      responsive sites for lamellipodia extensions during cell migration.
AB  - Caldesmon is believed to be one of the key regulators for actin dynamics and
      thereby cell polarity, membrane extension, and cell motility. We have shown
      previously that stress fiber formation and cell movement are severely impaired in
      the cells expressing human fibroblast caldesmon fragment defective in Ca2+/CaM
      binding sites. Both Ser458 and Ser489, adjacent to the Ca2+/CaM-binding sites,
      are phosphorylated by p21-activated kinase (PAK) in vitro. Here we report that
      Ser458 is phosphorylated in response to cell movement. We substituted Ser458 and
      Ser489 on C-terminal caldesmon (CaD39) with alanine or glutamic acid to mimic
      under-phosphorylated (CaD39-PAKA) or constitutively phosphorylated (CaD39-PAKE)
      caldesmon. In vitro, CaD39-PAKE, but not CaD39-PAKA, fails to inhibit myosin
      ATPase activity and exhibits reduced binding to Ca2+/CaM. When stably expressed
      in Chinese Hamster Ovary cells, both CaD39-PAKA and CaD39-PAKE incorporate into
      stress fibers and localize to the leading edge of the migrating cell. Expression
      of CaD39-PAKE, but not CaD39-PAKA, fails to protect stress fibers from
      cytochalasin depolymerization. However, both mutations inhibit cell polarization
      and lead to defects in membrane extension and cell migration. We conclude that
      phosphorylation of caldesmon by PAK is a dynamic process required to regulate
      actin dynamics and membrane protrusions in wound-induced cell migration.

PMID- 16800004
TI  - The effect of reduction in cross-validation intervals on the performance of
      multifactor dimensionality reduction.
AB  - Multifactor Dimensionality Reduction (MDR) was developed to detect genetic
      polymorphisms that present an increased risk of disease. Cross-validation (CV) is
      an important part of the MDR algorithm, as it prevents over-fitting and allows
      the predictive ability of a model to be evaluated. CV is a computationally
      intensive step in the MDR algorithm. Traditionally, MDR has been implemented
      using 10-fold CV. In order to reduce computation time and therefore allow MDR
      analysis to be applied to larger datasets, we evaluated the possibility of
      eliminating or reducing the number of CV intervals used for analysis. We found
      that eliminating CV made final model selection impossible, but that reducing the
      number of CV intervals from ten to five caused no loss of power, thereby reducing
      the computation time of the algorithm by half. The validity of this reduction was
      confirmed with data from an Alzheimer's disease (AD) study.

PMID- 16800005
TI  - Contrasting multi-site genotypic distributions among discordant quantitative
      phenotypes: the APOA1/C3/A4/A5 gene cluster and cardiovascular disease risk
      factors.
AB  - Most tests of association between DNA sequence variation and quantitative
      phenotypes in samples of randomly chosen individuals rely on specification of
      genotypic strata followed by comparison of phenotypes across these strata. This
      strategy often succeeds when phenotypic differences are caused by one or two
      single nucleotide polymorphisms (SNPs) among the surveyed markers. However, when
      multiple-SNP haplotypes account for observed phenotypic variation, identification
      of the best partitioning requires examination of an inordinate number of SNP
      combinations. An alternative approach is to rank individuals by their phenotypic
      measures and ask whether attributes of the genotypic variation show a non-random
      distribution along this phenotypic ranking. One simple version of this strategy
      selects the top and bottom tails of the distribution, and then tests whether
      genotypes from these two samples are drawn from a single population. This
      framework does not require the recovery of phased haplotypes and allows contrasts
      between large numbers of sites at once. We use a method based on this approach to
      identify associations between plasma triglyceride level, a risk factor for
      cardiovascular disease, and multi-site genotypes located in the APOA1/C3/A4/A5
      cluster of apolipoprotein genes in unrelated individuals (1,071 African-American
      females, 780 African-American males, 1,036 European-American females, and 930
      European-American males) sampled from four US cities as part of the Coronary
      Artery Risk Development in Young Adults (CARDIA) study. Method performance is
      investigated using simulations that model genealogical variation and different
      genetic architectures. Results indicate that this multi-site test can identify
      genotype-phenotype associations with reasonable power, including those generated
      by some simple epistatic models.

PMID- 16800006
TI  - Causal mapping as a tool to mechanistically interpret phenomena in cell motility:
      application to cortical oscillations in spreading cells.
AB  - Biological processes that occur at the cellular level and consist of large
      numbers of interacting elements are highly nonlinear and generally involve
      multiple time and spatial scales. The quantitative description of these complex
      systems is of great importance but presents large challenges. We outline a new
      systems biology approach, causal mapping (CMAP), which is a coarse-grained
      biological network tool that permits description of causal interactions between
      the elements of the network and overall system dynamics. On one hand, the CMAP is
      an intermediate between experiments and physical modeling, describing major
      requisite elements, their interactions and paths of causality propagation. On the
      other hand, the CMAP is an independent tool to explore the hierarchical
      organization of cell and the role of uncertainties in the system. It appears to
      be a promising easy-to-use technique for cell biologists to systematically probe
      verbally formulated qualitative hypotheses. We apply the CMAP to study the
      phenomenon of contractility oscillations in spreading cells in which microtubules
      have been depolymerized. The precise mechanism by which these oscillations are
      governed by a complex mechano-chemical system is not known but the data observed
      in experiments can be described by a CMAP. The CMAP suggests that the source of
      the oscillations results from the opposing effects of Rho activation leading to a
      decreased level of myosin light chain phosphatase and a cyclic calcium influx
      caused by increased membrane tension and leading to a periodically enhanced
      activation of myosin light chain kinase.

PMID- 16800007
TI  - Fatigue in primary biliary cirrhosis is associated with excessive daytime
      somnolence.
AB  - A significant proportion of patients with primary biliary cirrhosis (PBC) suffer
      from severe fatigue. The aim of this study was to characterize patterns of
      daytime sleep in patients with PBC (using both objective and subjective
      assessment approaches) and to study the association between sleep abnormality and
      fatigue severity. Fatigue severity was assessed in 48 female subjects with PBC
      (using a disease-specific quality of life instrument (the PBC-40) and a generic
      fatigue measure (Fatigue Impact Scale [FIS]) as well as 48 case-matched normal
      controls. All participants also completed the Pittsburgh Sleep Quality Index
      (PSQI) and the Epworth Sleepiness Scale (ESS, which assesses daytime
      hypersomnolence). Objective sleep assessment was performed using accelerometry
      over 7 days. Global sleep quality assessed by the PSQI was significantly lower in
      the PBC group compared to controls (P < .0001). ESS scores were significantly
      higher in patients with PBC than controls (P = .0001), suggesting significantly
      greater daytime somnolence in the patients with PBC. Objective sleep assessment
      confirmed that subjects with PBC were sleeping on average almost twice as long as
      controls during the daytime. Both degree of daytime somnolence (ESS) and actual
      daytime sleep activity (accelerometry) correlated strongly with fatigue severity
      in the patient group (r2 = 0.5, P < .0001 and r2 = 0.2, P < .01, respectively).
      In conclusion, Sleep abnormality, in the form of excessive daytime somnolence, is
      present in a significant proportion of patients with PBC, with the degree of
      daytime somnolence correlating strongly with the degree of fatigue. Existing
      agents effective at reducing daytime somnolence (such as modafinil) hold
      potential for the treatment of fatigue in PBC.

PMID- 16800008
TI  - Regio- and stereoselective palladium-pincer complex catalyzed allylation of
      sulfonylimines with trifluoro(allyl)borates and allylstannanes: a combined
      experimental and theoretical study.
AB  - Regio- and stereoselective palladium-pincer complex catalyzed allylation of
      sulfonylimines has been performed by using substituted trifluoro(allyl)borates
      and trimethylallylstannanes. The reactions provide the corresponding branched
      allylic products with excellent regioselectivity. The stereoselectivity of these
      processes is very high when trifluoro(cinnamyl)borate and trimethyl cinnamyl
      stannane are employed as allylic precursors; however, the reaction with
      trifluoro(crotyl)borate results in poor stereoselectivity. The major diastereomer
      formed in these reactions was the syn isomer, while the (previously reported)
      reactions with aldehyde electrophiles afforded the anti products, indicating that
      the mechanism of the stereoselection is dependent on the applied electrophile.
      Therefore, we have studied the mechanistic aspects of the allylation reactions by
      experimental studies and DFT modeling. The experimental mechanistic studies have
      clearly shown that potassium trifluoro(allyl)borate undergoes transmetallation
      with palladium-pincer complex 1 a affording an eta(1)-allylpalladium-pincer
      complex (1 e). The mechanism of the transfer of the allyl moiety from palladium
      to the sulfonylimine substrate was studied by DFT calculations at the
      B3PW91/LANL2DZ+P level of theory. These calculations have shown that the
      electrophilic substitution of sulfonylimines proceeds in a one-step process with
      a relatively low activation energy. The topology of the potential energy surface
      in the vicinity of the transition-state structure proved to be rather complicated
      as nine different geometries with similar energies were located as first order
      saddle points. Our studies have also shown that the high stereoselectivity with
      cinnamyl metal reagents stems from steric interactions in the TS structure of the
      allylation reaction. In addition, these studies have revealed that the mechanism
      of the stereoselection in the allylation of aldehydes and sulfonylimines is
      fundamentally different.

PMID- 16800009
TI  - Fluorogenic 1,3-dipolar cycloaddition within the hydrophobic core of a shell
      cross-linked nanoparticle.
AB  - Using either nitroxide mediated polymerization (NMP) or reversible addition
      fragmentation transfer (RAFT) techniques, novel block copolymers that present
      terminal acetylenes, in the side chain of the styrenic block, were obtained with
      narrow polydispersities and targeted molecular weights. For the conversion of
      these acetylene-functionalized polymers to amphiphilic block copolymers, RAFT
      techniques were preferred. Mild protection/deprotection chemistries were employed
      which were compatible with the incorporation of the acetylene functionality in
      the hydrophobic segment. These acetylene-functionalized, Click-readied
      amphiphilic block copolymers were then self-assembled and cross-linked to afford
      shell cross-linked knedel-like (SCK) nanoparticles that contained acetylene
      groups in the core domain. The hydrodynamic diameters (D(h)) of the block
      copolymer micelles and nanoparticles were determined by dynamic light scattering
      (DLS), and the dimensions of the nanoparticles were characterized using tapping
      mode atomic force microscopy (AFM) and transmission electron microscopy (TEM).
      The chemical availability of the Click functionality within the core domain of
      the SCKs was investigated using the copper(I)-catalyzed 1,3-dipolar fluorogenic
      cycloaddition with a non-fluorescent 3-azidocoumarin profluorophore to afford
      intensely fluorescent nanoparticles.

PMID- 16800010
TI  - Conjecture: imines as unidirectional photodriven molecular motors-motional and
      constitutional dynamic devices.
AB  - Compounds containing the C==N group, such as imines and their derivatives, may
      undergo syn-anti isomerization by two different routes: 1) photochemically, by
      out-of-plane rotation around the carbon-nitrogen double bond through a
      "perpendicular" form, and 2) thermally, by in-plane nitrogen inversion through a
      "linear" transition state. When the two interconversions occur in sequence, a
      full, closed process is accomplished, restoring the initial state of the system
      along two different steps. In a chiral imine-type compound, for example, with an
      asymmetric center next to the C==N function, photoinduced rotation may be
      expected to occur in one sense in preference to the opposite one. Thus,
      photoisomerization followed by thermal isomerization in a chiral imine compound
      generates unidirectional molecular motion. Generally, imine-type compounds
      represent unidirectional molecular photomotors converting light energy into
      mechanical motion. As they are also able to undergo exchange of the carbonyl and
      amine partners, they present constitutional dynamics. Thus, imine-type compounds
      are double dynamic, motional, and constitutional devices.

PMID- 16800011
TI  - Deep blue mixed-valent PtIIIPtIIIPtII complex [Pt3Br2(mu-pz)6] (pz=pyrazolate)
      showing valence-detrapping behavior in solution.
AB  - The oxidation of the pyrazolate bridged cyclic PtII trimer, [Pt3(mu-pz)6] (1), in
      the presence of bromide ion gave a deep blue mixed-valent Pt(II,III,III) complex,
      [Pt3Br2(mu-pz)6] (2). The structural analysis of 2 disclosed that the complex has
      localized Pt--Pt bond. Our theoretical calculations revealed that the HOMO and
      LUMO of Pt3 (II,III,III) species mainly consists of (dsigma-dsigma) and (dsigma
      dsigma)* orbitals, respectively, and the origin of deep blue color of the bromo
      complex, 2, arises from the (dsigma-dsigma)-->(dsigma-dsigma)* transition. Unique
      fluxional behavior was observed due to valence-detrapping of 2 in solution. The
      activation parameters of the valence-detrapping of 2 obtained by Eyring analyses
      were DeltaH(not equal)=37(2) kJ mol(-1) and DeltaS(not equal)=-67(7) J mol(-1) K(
      1).

PMID- 16800012
TI  - Biocatalytic evolution of a biocatalyst marker: towards the ultrasensitive
      detection of immunocomplexes and DNA analysis.

PMID- 16800013
TI  - Visible-light photochromism of bis(ferrocenylethynyl)ethenes switches electronic
      communication between ferrocene sites.

PMID- 16800014
TI  - Stepwise solid-phase synthesis and spontaneous homodimerization of the helix-loop
      helix protein Id3.

PMID- 16800015
TI  - Endohexosaminidase M: exploring and exploiting enzyme substrate specificity.

PMID- 16800016
TI  - Calcite mesocrystals: "morphing" crystals by a polyelectrolyte.
AB  - Crystallization of calcite from different concentrated calcium chloride solutions
      by the CO(2) vapor diffusion technique in the presence of polystyrenesulfonate
      (PSS) yields defined assemblies of nanoparticles with unusual morphology. From
      the typical calcite rhombohedra, the morphology can be systematically varied via
      rounded edges and truncated triangles to concavely bent lens-like shapes.
      Although these "crystals" are apparently well facetted as observed in light
      microscopy, electron microscopy analysis and BET isotherms reveal that the
      structures are highly porous and are composed of almost perfectly three
      dimensionally aligned calcite nanocrystals, scaffolded to the final, partly
      curved structures. The formation of all mesostructures is discussed within the
      framework of a polymer-mediated structure-formation process, in which the polymer
      is acting in four different ways. The present model case also provides evidence
      for the importance of nonclassical mesoscopic processes in polymer-controlled
      crystallization in general.

PMID- 16800017
TI  - Photoinduced electron transfer in alpha-cyclodextrin-based supramolecular dyads:
      a free-energy-dependence study.
AB  - Photoinduced electron transfer (PET) between alpha-cyclodextrin-appended pyrene
      (PYCD) and a few acceptor molecules was studied in aqueous solutions. The pyrene
      moiety in PYCD is located above the narrower rim of the alpha-CD and is fully
      exposed to water. The acceptors are monocyclic organic molecules and, upon
      dissolution in water in the presence of PYCD, a fraction of the donor-acceptor
      systems is present as supramolecular dyads and the remaining fraction as free
      molecules. Free-energy-dependence studies showed that electron transfer in the
      supramolecular dyads follows the Marcus equation. The donor-acceptor coupling and
      the reorganization energy were determined from fits of the data to the Marcus
      equation. The electronic coupling was found to be similar to those reported for
      hydrogen-bonded systems. It appears that the actual lambdaout values are somewhat
      lower than values calculated with the continuum model. The experimental design
      has also allowed, for the first time, a visual demonstration of the inverted
      region on the basis of the raw fluorescence lifetime data.

PMID- 16800018
TI  - Assembly-controlled biocompatible interface on a microchip: strategy to highly
      efficient proteolysis.
AB  - A biocompatible interface was constructed on a microchip by using the layer-by
      layer (LBL) assembly of charged polysaccharides incorporating proteases for
      highly efficient proteolysis. The controlled assembly of natural polyelectrolytes
      and the enzyme-adsorption step were monitored by using a quartz-crystal
      microbalance and atomic force microscopy (AFM). Such a multilayer-assembled
      membrane provides a biocompatible interconnected network with high enzyme-loading
      capacity. The maximum digestion rate of the adsorbed trypsin in a microchannel
      was significantly accelerated to 1600 mM min(-1) microg(-1), compared with the
      tryptic digestion in solution. Based on the Langmuir isotherm model, the
      thermodynamic constant of adsorption K was calculated to be 1.6 x 10(5) M(-1) and
      the maximum adsorption loading Gammamax was 3.6 x 10(-6) mol m(-2), 30 times more
      than a monolayer of trypsin on the native surface. The tunable interface
      containing trypsin was employed to construct a microchip reactor for digestion of
      femtomoles of proteins and the produced peptides were analyzed by MALDI-TOF mass
      spectroscopy. The efficient on-chip proteolysis was obtained within a few
      seconds, and the identification of biological samples was feasible.

PMID- 16800019
TI  - Flexibility of inorganic tennis ball structures inducing anion selectivity.
AB  - Inorganic tennis balls (ITBs), [[{Pt(betmp)(dach)}(2)Cu](2)(X)][X](3) (in which
      X=ClO(4) (-) (3), NO(3) (-) (4), Cl(-) (5) and Br(-) (6); dach=trans-1,2
      diaminocyclohexane and betmp=bisethylthiomethylidenepropanedioate) and
      [[{Pt(dteym)(dach)}(2)Cu](2)(PF(6))][PF(6)](3) (7; dteym=1,3-dithiepane-2
      ylidenemalonate), were prepared as crystals. Investigation of their X-ray crystal
      structures revealed that shapes of the cavities in ITBs show significant
      distortions that depend on the properties of the encapsulated anions. The CuCu*
      distance was observed to be longest in 7 and shortest in 5, the difference
      between them being 2.05 A. The flexibility of cavity structures of ITBs makes it
      possible to encapsulate various anions inside the cavity, while their distortions
      may be a reason for the difference in the encapsulating ability for anions, that
      is, anion selectivity. Especially, the distortions observed in 7 are so severe
      that the encapsulating ability of the cavity for PF(6) (-) is very low compared
      to other anions. The shapes of ITBs with ClO(4) (-) and BF(4) (-) ions inside
      their cavities are very similar; however, ClO(4) (-) is encapsulated by the
      cavity better than BF(4) (-), which is explicable by the difference of metal
      anion interactions. This structural study on ITBs gives a clue to the origin of
      the anion selectivity of the cavity in ITBs previously investigated by (19)F NMR
      spectroscopy of the ITBs in methanol.

PMID- 16800020
TI  - Covalent connection of individualized, neutral, dendronized polymers on a solid
      substrate using a scanning force microscope.
AB  - The synthesis of a neutral, high-molar-mass, acrylamide-based, third-generation
      dendronized polymer (denpol) with a defined number of azide groups at its
      periphery is reported. An attach-to route is used in which a first-generation
      denpol is reacted with second-generation (G2) dendrons. The degree of structure
      perfection of the resulting denpol is quantified as 99.8 %. This value was
      obtained after the introduction of a fluorescence label at the sites that
      remained unaffected by the dendronization. The high coverage was independently
      confirmed for the dendronization of another first-generation polymer and a
      closely related G2 dendron. The third-generation denpol resulting from the first
      dendronization experiment was spin-coated as a sub-monolayer onto highly oriented
      graphite precoated with an ultrathin layer of C12H25NH2, which was introduced to
      provide a well-defined substrate for denpol adsorption and manipulation. Scanning
      force microscopy revealed single denpols, which could be moved across the surface
      and "welded" by covalent cross-linking induced by photochemical decomposition of
      the azides into highly reactive nitrenes. The successful formation of covalent
      bonds between two denpols was confirmed by mechanically challenging the link with
      the scanning force microscope (SFM) tip. This is the second reported case of a
      move-connect-prove sequence using polymers and the SFM, which for the first time
      employs noncharged denpols, thus widening the applicability of this method
      significantly.

PMID- 16800021
TI  - o-DPPB-directed copper-mediated and -catalyzed allylic substitution with Grignard
      reagents.
AB  - The ortho-diphenylphosphanylbenzoyl (o-DPPB) group was explored as a directing
      leaving group in copper-mediated and copper-catalyzed allylic substitution with
      Grignard reagents. Complete control of chemo-, regio- and stereoselectivity with
      complete syn-1,3-chirality transfer was observed as a result of the directed
      nature of the reaction. No excess of organometallic reagent is required and the
      directing group can be recovered quantitatively. Coordination studies in the
      solid state and in solution have shown that two substrates are bound via the
      phosphine function of the directing group at copper. Dynamic NMR experiments in
      solution are in agreement with a ligand-exchange process at copper, a
      prerequisite for the development of a substoichiometric process.

PMID- 16800022
TI  - Highly efficient synthesis of enantiopure diacetylated C(2)-symmetric diols by
      ruthenium- and enzyme-catalyzed dynamic kinetic asymmetric transformation
      (DYKAT).
AB  - Highly efficient synthesis of enantiopure diacetates of 2,4-pentanediol and 2,5
      hexanediol starting from commercially available mixtures of the diols (dl/meso
      approximately 1:1) has been realized by combining a fast ruthenium-catalyzed
      epimerization with an enzymatic transesterification. The in situ coupling of
      these two processes produces the diacetates in high yield in >99 % enantiomeric
      excess.

PMID- 16800023
TI  - S-thiazolinyl (STaz) glycosides as versatile building blocks for convergent
      selective, chemoselective, and orthogonal oligosaccharide synthesis.
AB  - In the aim of developing new procedures for efficient oligosaccharide assembly, a
      range of S-thiazolinyl (STaz) glycosides have been synthesized. These novel
      derivatives were evaluated against a variety of reaction conditions and were
      shown to be capable of being chemoselectively activated in the armed-disarmed
      fashion. Moreover, the S-thiazolinyl moiety exhibited a remarkable propensity for
      selective activation over other common leaving groups. Conversely, a variety of
      leaving groups could be selectively activated over the STaz moiety, which, in
      turn, allowed STaz/S-ethyl and STaz/S-phenyl orthogonal approaches. To
      demonstrate versatility of novel STaz derivatives, a number of oligosaccharide
      targets have been synthesized in a convergent selective, orthogonal, and
      chemoselective fashion.

PMID- 16800024
TI  - A high efficiency cloning and expression system for proteomic analysis.
AB  - The recent description of the complete genomes of the two most pathogenic species
      of Brucella opens the way for genome-based analysis of the antigenicity of their
      proteins. In the present report, we describe a bench-level high-efficiency
      cloning and expression system (HECES) that allow expression of large numbers of
      Brucella proteins based on genomic sequence information. Purified proteins are
      produced with high efficiency in a microarray format conducive to analysis of
      their sero-reactivity against serum from immunized animals. This method is
      applicable at either small or large scale of protein processing. While it does
      not require robotics, the format is amenable to robotic implementation for all
      aspects of the process and subsequent analysis of protein characteristics. This
      method will allow selection of new reagents for diagnosis of brucellosis and
      development of vaccine against Brucella, an important zoonotic disease and
      biothreat agent.

PMID- 16800025
TI  - Novel design of multicapillary arrays for high-throughput DNA sequencing.
AB  - A novel approach to design and optimize linear multicapillary arrays (LMCAs) for
      high-throughput DNA sequencing is proposed. A significant increase in the number
      of capillary lanes is obtained due to the use of composite insertions alternately
      placed between working capillaries of the array and a specific combination of
      refractive indices of the DNA separation matrix, capillary glass, the insertions
      and a medium which surrounds the capillary array. Theoretical and experimental
      studies showed that in conjunction with a dual-side laser illumination scheme,
      the proposed LMCA design allows a simultaneous uniform irradiation of as many as
      550 working capillaries.

PMID- 16800026
TI  - Effect of staining reagent on peptide mass fingerprinting from in-gel trypsin
      digestions: a comparison of SyproRuby and DeepPurple.
AB  - As the new fluorescent stains such as SyproRuby and DeepPurple are getting
      widespread recognition for proteome analyses by the traditional 2-D gel method,
      it becomes important to test the feasibility of these stains with respect to
      staining reproducibility, protein quantitation, and compatibility of the stain
      with downstream MS. The binding of epicocconone, active ingredient of DeepPurple,
      to one of the primary cleavage sites of trypsin (lysine residue) raises the
      possibility of incomplete cleavage and interference with PMF. However, the
      current study tests and concludes that the DeepPurple stain can result in
      increased peptide recovery compared to SyproRuby stain and can improve MS-based
      identification of lower intensity proteins spots.

PMID- 16800027
TI  - On-capillary derivatization and analysis of amino acids in human plasma by
      capillary electrophoresis with laser-induced fluorescence detection: application
      to diagnosis of aminoacidopathies.
AB  - A capillary electrophoresis with laser-induced fluorescence detection method for
      the analysis of free amino acids (AA) in human plasma was developed. A mixture of
      16 AA was on-capillary derivatized with 3-(2-furoyl)quinoline-2-carboxaldehyde
      (FQ) and separated inside the capillary in less than 30 min using 70 mM borax-3.5
      mM SDS pH 9.3 as running buffer. Four plasma samples from a healthy donor and
      patients suffering from phenylketonuria, propionic acidemia, and tyrosinemia type
      II were studied. Repeatabilities calculated as intra-day RSD (n = 3) values for
      the AA involved in these aminoacidopathies (glycine, phenylalanine, and tyrosine)
      were in the range of 0.3 to 1.2% for migration time and 3.7 to 8.2% for peak
      height. Reproducibilities calculated as inter-day RSD (n = 4) values for the same
      AA were between 0.7 and 1.4% for migration time and 4.7 and 9.1% for peak height.
      A fast qualitative analysis allowed the identification of the corresponding
      disease by comparing the electrophoretic profiles from the patient and the
      healthy donor and noting the increased level of the specific AA accompanying each
      individual disease. The results of the quantitative analysis for glycine,
      phenylalanine, and tyrosine in the plasma samples studied using the developed
      method showed a good agreement with those provided by the Center of Diagnosis of
      Molecular Diseases using a standard method for AA analysis.

PMID- 16800028
TI  - Highly sensitive determination of lanthanides by capillary electrophoresis with
      direct visible detection after precapillary complexation with aromatic
      polyaminocarboxylate and additionally applying dynamic ternary complexation with
      nitrilotriacetic acid.
AB  - A newly synthesized aromatic polyaminocarboxylate (NBD-ABEDTA, H(4)L) was applied
      to precapillary derivatizing capillary electrophoresis as a chelating reagent for
      lanthanide ions (Ln(3+)). The Ln-L complexes provide both kinetic stability on
      dissociation due to their methyl-EDTA coordinating structure, and high light
      absorptivity (epsilon(max) = 2.4 x 10(4) cm(-1) mol(-1) dm(3)) in the visible
      region at 469 nm thanks to their nitrobenzofurazan moiety. A ligand was employed
      for capillary zone electrophoresis based on a unique concept: both precapillary
      and dynamic on-capillary complexation were carried out on one center-metal ion to
      achieve high resolution. As a ternary complex-formation agent, iminodiacetate
      (IDA), bound to the mother complex (Ln-L), was added to the carrier buffer
      solution. The carrier buffer solution of 9.5 mmol.dm(-3) (pH 9.45) borate and
      33.5 mmol.dm(-3) IDA, drastically improved the resolution among Ln(3+) ions. Each
      of the Ln complexes was effectively separated, except for Pr-Sm. Furthermore, the
      absence of L from the carrier solution, which stabilizes the baseline
      fluctuation, provided low LOD (typically 4.2 x 10(-7) mol.dm(-3)). This strongly
      suggests that Ln-L complexes are kinetically stable even with a large excess of
      IDA. Quite unexpectedly, the order of migration differs from that of the atomic
      number, inverting at Nd. This is due to the effect of the cavity size of the
      residual coordination sites on the ternary complexation and the electronic
      density of Ln(3+).

PMID- 16800030
TI  - Perphenylcarbamoylated beta-cyclodextrin bonded-silica particles as chiral
      stationary phase for enantioseparation by pressure-assisted capillary
      electrochromatography.
AB  - Perphenylcarbamoylated beta-cyclodextrin bonded-silica particles (5 microm) were
      packed into 75-mum fused-silica capillaries, and used for the enantiomer
      separation of neutral and basic solutes by pressure-assisted capillary
      electrochromatography. Triethylammonium acetate and phosphate buffer were
      employed as the BGEs. A cathodic EOF was observed with these two BGEs. Seven
      chiral analytes were successfully resolved into their enantiomers under optimized
      conditions, and five of them could be baseline-separated within 12 min due to
      their high electrophoretic mobility. Better results were achieved with phosphate
      buffer as the BGE. The effects of organic content and pH on the enantioseparation
      were also investigated.

PMID- 16800029
TI  - Large-scale pyrosequencing of synthetic DNA: a comparison with results from
      Sanger dideoxy sequencing.
AB  - Pyrosequencing is a relatively recent method for sequencing short stretches of
      DNA. Because both Pyrosequencing and Sanger dideoxy sequencing were recently used
      to characterize and validate DNA molecular barcodes in a large yeast gene
      deletion project, a meta-analysis of those data allow an excellent and timely
      opportunity for evaluating Pyrosequencing against the current gold standard,
      Sanger dideoxy sequencing. Starting with yeast genomic DNA, parallel PCR
      amplification methods were used to prepared 4747 short barcode-containing
      constructs from 6000 Saccharomyces cerevisiae gene-deletion strains.
      Pyrosequencing was optimized for average read lengths of 25-30 bases, which
      included in each case a 20-mer barcode sequence. Results were compared with
      sequence data obtained by the standard Sanger dideoxy chain termination method.
      In most cases, sequences obtained by Pyrosequencing and Sanger dideoxy sequencing
      were of comparable accuracy, and the overall rate of failure was similar. The DNA
      in the barcodes is derived from synthetic oligonucleotide sequences that were
      inserted into yeast-deletion-strain genomic DNA by homologous recombination and
      represents the most significant amount of DNA from a synthetic source that has
      been sequenced to date. Although more automation and quality control measures are
      needed, Pyrosequencing was shown to be a fast and convenient method for
      determining short stretches of DNA sequence.

PMID- 16800031
TI  - The unified equation for the evaluation of degenerated first-order reactions in
      dynamic electrophoresis.
AB  - An analytical solution for the unified equation for degenerated (pseudo-) first
      order reactions, e.g., enantiomerization processes, in dynamic CE is presented,
      and validated with a dataset of 31 250 elution profiles covering typical
      experimental parameters. The unified equation was applied to determine the
      enantiomerization barrier of the hypnotic glutarimide derivative thalidomide
      (Contergan(R)) by dynamic capillary electrokinetic chromatography (DEKC). The
      enantiomer separation of thalidomide was performed in an aqueous 50 mM sodium
      borate buffer at pH 9.3 in the presence of the chiral mobile phase additive
      carboxymethyl-beta-CD. Interconversion profiles featuring pronounced plateau
      formation were observed. Activation parameters DeltaH( not equal) and DeltaS( not
      equal) were obtained from temperature-dependent measurements between 20.0 and
      37.5 degrees C in 2.5K steps. From the activation parameters the
      enantiomerization barrier of thalidomide at 37 degrees C under basic conditions
      were calculated to be DeltaG( not equal) = 93.2 kJ/mol. Comparison of the kinetic
      data with results obtained at pH 8.0 reveals the catalytic influence of the base
      on the enantiomerization barrier.

PMID- 16800033
TI  - Primary amine coding as a path to comparative proteomics.
AB  - Various isotope coding strategies are being used today in the field of
      comparative proteomics. This article specifically reviews the strengths and
      limitations of various N-termini-directing strategies. N-termini-directed coding
      strategy allows for use of different chromatographic enrichment techniques. Since
      N-termini-directed coding strategies are global in nature, they can be utilized
      in studying PTMs as well as protein expression. Using different N-termini
      directed coding strategies, both relative and absolute quantification of proteins
      can be achieved either in the MS mode or in the MS/MS mode. The review ends with
      the conclusion that significant improvements have been made in the last decade.
      Among various issues, a need still exists for a better understanding of the
      kinetic issues in proteomics, relative protein pool sizes for different proteins
      and the issue of stimulus-induced changes in protein aggregation. Another
      critical issue that needs to be addressed in great detail is the role of PTMs in
      regulation.

PMID- 16800032
TI  - Protein changes between dormant and dormancy-broken seeds of Prunus campanulata
      Maxim.
AB  - Seed dormancy is regulated by complex networks in order to optimize the timing of
      germination. However, the biochemical basis of the regulation of seed dormancy is
      still poorly understood. Many temperate timber species, which are of ecological
      and/or economic interest, are deeply dormant in seeds, such as Prunus
      campanulata. Freshly harvested seeds require warm plus cold stratification to
      break dormancy before they can begin to germinate. According to the results of
      germination, both warm and cold stratifications are the critical influences for
      breaking seed dormancy. Significant variations in seed proteins were observed by
      2-DE before and after the breaking of seed dormancy. Among the 320, 455, and 491
      reproducibly detected spots on the cotyledons, embryos, and testae, respectively,
      71 dramatic changes in abundances were observed following warm and/or cold
      stratification. Among these protein spots, dehydrin, prunin 1 precursor, prunin 2
      precursor, and prunin 2 were identified by MS and sequence comparison. The
      implications of protein changes in relation to the breaking of seed dormancy and
      germination are discussed. This is the first report of a proteomic analysis of
      dormancy breaking in woody plant seeds.

PMID- 16800034
TI  - Protein Equalizer Technology : the quest for a "democratic proteome".
AB  - No proteome can be considered "democratic", but rather "oligarchic", since a few
      proteins dominate the landscape and often obliterate the signal of the rare ones.
      This is the reason why most scientists lament that, in proteome analysis, the
      same set of abundant proteins is seen again and again. A host of pre
      fractionation techniques have been described, but all of them, one way or
      another, are besieged by problems, in that they are based on a "depletion
      principle", i.e. getting rid of the unwanted species. Yet "democracy" calls not
      for killing the enemy, but for giving "equal rights" to all people. One way to
      achieve that would be the use of "Protein Equalizer Technology" for reducing
      protein concentration differences. This comprises a diverse library of
      combinatorial ligands coupled to spherical porous beads. When these beads come
      into contact with complex proteomes (e.g. human urine and serum, egg white, and
      any cell lysate, for that matter) of widely differing protein composition and
      relative abundances, they are able to "equalize" the protein population, by
      sharply reducing the concentration of the most abundant components, while
      simultaneously enhancing the concentration of the most dilute species. It is felt
      that this novel method could offer a strong step forward in bringing the "unseen
      proteome" (due to either low abundance and/or presence of interference) within
      the detection capabilities of current proteomics detection methods. Examples are
      given of equalization of human urine and serum samples, resulting in the
      discovery of a host of proteins never reported before. Additionally, these beads
      can be used to remove host cell proteins from purified recombinant proteins or
      protein purified from natural sources that are intended for human consumption.
      These proteins typically reach purities of the order of 98%: higher purities
      often become prohibitively expensive. Yet, if incubated with "equalizer beads",
      these last impurities can be effectively removed at a small cost and with minute
      losses of the main, valuable product.

PMID- 16800035
TI  - Comparative proteomics of high light stress in the model alga Chlamydomonas
      reinhardtii.
AB  - High light (HL) stress adversely affects growth, productivity and viability of
      photosynthetic organisms. The green alga Chlamydomonas reinhardtii is a model
      system to study photosynthesis and light stress. Comparative proteomics of wild
      type and two very high light (VHL)-resistant mutants, VHL(R)-S4 and VHL(R)-S9,
      revealed complex alterations in response to excess light. A two-dimensional
      reference map of the soluble subproteome was constructed representing about 1500
      proteins. A total of 83 proteins from various metabolic pathways were identified
      by peptide mass fingerprinting. Quantitative comparisons of 444 proteins showed
      105 significantly changed proteins between wild type and mutants under different
      light conditions. Commonly, more proteins were decreased than increased, but
      different proteins were affected in each genotype. Proteins uniquely altered in
      either VHL(R) mutant may be involved in VHL resistance. Such candidate proteins
      similarly altered without light stress, thus possibly contributing to "pre
      adaptation" of mutants to VHL, included decreased levels of a DEAD box RNA
      helicase (VHL(R)-S4) and NAB1 and RB38 proteins (VHL(R)-S9), and increased levels
      of an oxygen evolving enhancer 1 (OEE1) isoform and an unknown protein (VHL(R)
      S4). Changes from increased levels in HL to decreased levels in excess light,
      included OEE1 (VHL(R)-S9) or the reverse change for NAB1, RB38, beta-carbonic
      anhydrase and an ABC transporter-like protein (VHL(R)-S4).

PMID- 16800036
TI  - Mass spectrometric analysis of formalin-fixed paraffin-embedded tissue: unlocking
      the proteome within.
AB  - The predominance of tissues stored worldwide in hospitals and clinical
      laboratories exist in formalin-fixed paraffin-embedded (FFPE) blocks that are
      generated by simple and well-established protocols. Although generation of FFPE
      tissues has facilitated their characterization by such techniques as
      histopathology, they have proven refractory to biomarker discovery investigations
      using state-of-the-art MS-based proteomic methodologies. Very recently new
      methods have been developed that enable proteins extracted from FFPE tissues to
      be analyzed by MS. This review will highlight and discuss those efforts that have
      led to this exciting recent progress. Although these developments are quite new,
      the ability to conduct MS-based proteomic analyses of FFPE tissues opens
      heretofore intractable clinical samples for discovery-based biomarker research.

PMID- 16800039
TI  - Primary health care and phytomedicine in Argentina.

PMID- 16800037
TI  - Optimized proteomic analysis of a mouse model of cerebellar dysfunction using
      amine-specific isobaric tags.
AB  - Recent proteomic applications have demonstrated their potential for revealing the
      molecular mechanisms underlying neurodegeneration. The present study quantifies
      cerebellar protein changes in mice that are deficient in plasma membrane calcium
      ATPase 2 (PMCA2), an essential neuronal pump that extrudes calcium from cells and
      is abundantly expressed in Purkinje neurons. PMCA2-null mice display motor
      dyscoordination and unsteady gait deficits observed in neurological diseases such
      as multiple sclerosis and ataxia. We optimized an amine-specific isobaric tags
      (iTRAQ)-based shotgun proteomics workflow for this study. This workflow took
      consideration of analytical variance as a function of ion signal intensity and
      employed biological repeats to aid noise reduction. Even with stringent protein
      identification criteria, we could reliably quantify nearly 1000 proteins,
      including many neuronal proteins that are important for synaptic function. We
      identified 21 proteins that were differentially expressed in PMCA2-null mice.
      These proteins are involved in calcium homeostasis, cell structure and chromosome
      organization. Our findings shed light on the molecular changes that underlie the
      neurological deficits observed in PMCA2-null mice. The optimized workflow
      presented here will be valuable for others who plan to implement the iTRAQ
      method.

PMID- 16800041
TI  - Humoral immune responses against minute virus of mice vectors.
AB  - BACKGROUND: Owing to their oncolytic properties, autonomous rodent parvoviruses
      and derived vectors constitute potential anti-tumor agents. METHODS: Humoral
      immune responses to minute virus of mice (MVMp) were characterized. In
      particular, the generation of neutralizing antibodies on subsequent therapeutic
      virus applications was evaluated in a mouse melanoma model. Mice bearing
      subcutaneous melanomas were injected intratumorally with virus and re-injected 10
      days later in a second tumor on the other flank. Four days after the first or
      second injection, the tumors and lymph nodes were analyzed by RT-PCR for gene
      expression. RESULTS: Injection of MVMp in tumor-bearing B6 mice resulted in viral
      gene expression in tumors and draining lymph nodes. A repeated virus
      administration did not lead to detectable viral transcription if it was preceded
      by a virus infection 10 days earlier. This protection correlated with the
      induction of virus-neutralizing antibodies following the first virus application.
      The restrictions on viral gene expression after a consecutive MVMp injection
      could be alleviated in subsequent applications by the use of viruses consisting
      of MVMp genomes packaged into capsids of a related parvovirus. Neutralizing
      antibody induction was irrespective of the route of administration and of the
      presence of a tumor and persisted at significant levels at least up to 26 weeks
      after the viral infection. MVMp infection of B6 mice stimulated the generation of
      IgM and IgG anti-viral antibodies, the latter mainly of the T-helper (Th) 1
      dependent IgG2, and the T-cell-independent IgG3 subclasses. CONCLUSIONS:
      Neutralizing antibodies impede the effectiveness of a subsequent virus
      administration, but can be overcome by pseudotyping.

PMID- 16800042
TI  - What is bursitis?

PMID- 16800043
TI  - As AIDS drugs fail thousands, "salvage" is key.

PMID- 16800044
TI  - HIV disclosure holds no added risk.

PMID- 16800045
TI  - Outbreak news. Plague, Democratic Republic of the Congo.

PMID- 16800046
TI  - Looking at biofuels and bioenergy.

PMID- 16800047
TI  - Looking at biofuels and bioenergy.

PMID- 16800048
TI  - Energy returns on ethanol production.

PMID- 16800049
TI  - Energy returns on ethanol production.

PMID- 16800050
TI  - Energy returns on ethanol production.

PMID- 16800051
TI  - Energy returns on ethanol production.

PMID- 16800052
TI  - Development of restricted-access media supports and their application to the
      direct analysis of biological fluid samples via high-performance liquid
      chromatography.
AB  - A quick overview of published methods for analyzing compounds in complex
      biological samples reveals that the most difficult step is the clean-up or
      extraction of a required compound from the matrix. The strategy required to
      analyze exogenous compounds in biological fluids depends greatly upon the nature
      of the compound and upon the biomatrix. Coupled-column separation using
      restricted-access media as the first dimension in order to exclude macromolecules
      and retain micromolecules has been successfully used for a number of biological
      fluids. This paper presents the history of the development of restricted-access
      media supports and of their application to the direct injection of biological
      fluid samples in high-performance liquid chromatography.

PMID- 16800053
TI  - Oral pathology quiz #35. Case number 3. Odontoma.

PMID- 16800054
TI  - Oral pathology quiz #35. Case number 4. Pemphigus vulgaris.

PMID- 16800055
TI  - Oral pathology quiz #45. Case number 3. Apical scar.

PMID- 16800057
TI  - Oral pathology quiz #48. Case number 3. Residual cyst.

PMID- 16800056
TI  - Oral pathology quiz #45. Case number 4. Traumatic bone cyst.

PMID- 16800058
TI  - Oral pathology quiz #43. Case number 3. Pyogenic granuloma.

PMID- 16800059
TI  - Oral pathology quiz #51. Case number 2. Mucus escape reaction or "mucocele".

PMID- 16800060
TI  - Oral pathology quiz #51. Case number 4. Focal epithelial hyperplasia.

PMID- 16800061
TI  - Breastfeeding a preterm infant and the objectification of breastmilk.
AB  - This paper presents the theme of objectification of breastmilk, which results
      from long-term breast expression by parents of hospitalised very low birth eight
      (VLBW) preterm infants. An interpretive phenomenological study, involving 17
      Australian parents was undertaken to explore parents' experiences of
      breastfeeding very low birth weight preterm infants from birth to twelve months
      of age. The discussion presented here is elicited from 45 individual interviews
      held with both mothers and fathers, which were then transcribed verbatim and
      analysed using thematic analysis. Objectification of breastmilk was one of the
      prevalent themes throughout all of the interviews. The effects of this
      objectification on the parents and their lactational experience will be
      discussed. Objectification of the breastfeeding experience, it will be shown, is
      incongruent with the parents' expectations and has a negative impact on their
      breastfeeding experience.

PMID- 16800062
TI  - Breastfeeding influences on growth and health at one year of age.
AB  - Our aim was to determine whether a longer duration of full breastfeeding in early
      infancy acts positively upon health outcomes. Women participating in a birth
      cohort study in Perth, Australia were followed-up at regular intervals to 52
      weeks. Infant feeding, socio-demographic and health-related data were collected.
      Infants fully breastfed for less than four weeks compared to infants fully
      breastfed for four weeks or longer had more health problems (odds ratio [OR]
      1.44; 95% confidence interval [CI] 1.00, 2.08; P = 0.048), more doctor visits (OR
      1.55; 95% CI 1.04, 2.33; P = 0.032) and poorer maternal rating of child health
      (OR 2.42; 95% CI 1.44, 4.06; P = 0.001) at four weeks. By 52 weeks, formula-fed
      infants were heavier (10138 g vs 9731 g, P = 0.041) and longer (75.6 cm vs 73.7
      cm, P = 0.011). An adverse effect of formula milk on infant health and postnatal
      weight gain remains of public health relevance.

PMID- 16800063
TI  - The ten steps to successful breastfeeding in Australian hospitals.
AB  - Breastfeeding is universally acknowledged as important for the well-being of
      mothers and babies. The ten steps to successful breastfeeding have been promoted
      as a means of improving breastfeeding initiation and maintenance. This study
      aimed to assess the degree of implementation of the ten steps within Australian
      maternity hospitals and collect breastfeeding rates at discharge. A 55-term
      questionnaire, modified for Australian conditions, was mailed to all Australian
      hospitals listed as providing maternity care in the 1998 Hospital and Health
      Services Yearbook. Of 432 hospitals currently providing maternity care, 387 (90%)
      responded. High rates of implementation of steps 1a, 3, 4, 5 6, 8 and 9 were
      reported. The mean rate of women breastfeeding at discharge, from 283 responses,
      was 88%. Australian hospitals compare favourably with similar studies in
      international environments. Results from this study may be used to target areas
      for improvements in steps 1b, 2, 7 and 10. Australia-wide breastfeeding rates at
      discharge have not changed since 1983.

PMID- 16800065
TI  - 5th World Workshop on Oral Health and Disease in AIDS. Proceedings of the
      Workshop. Phuket, Thailand. July 6-9, 2004.

PMID- 16800066
TI  - [Anatomic variations of the ilio-caval junction encountered in disk prosthesis
      implantation].
AB  - PURPOSE OF THE STUDY: The retroperitoneal mini-invasive anterior approach to the
      lumbar spine is widely used for disc excision and insertion of a prosthetic disc.
      A large operating window is needed. Venous wounds constitute one of the most
      serious complications. We analyzed the angle and position of the iliocaval on the
      preoperative angio-MRI in search for correlations with the intraoperative
      findings. Our aim was to determine whether the preoperative angio-MRI gives
      indications concerning the operative difficulty and the best strategy for
      prosthesis fitting. MATERIAL AND METHOD: This prospective study included 35
      consecutive patients who underwent surgery for implantation of a Maverick disc
      prosthesis. Average patient age was 46.7 years. The indication for surgery was
      isolated degenerative discopathy with invalidating chronic low back pain without
      alteration of the muscle masse or facet joints. A preoperative angio-MRI was
      performed with T1 spin-echo sequences for the coronal slices and T2 axial slices
      passing through the upper extremity of the L5-S1 disc. We searched for
      correlations between the MRI and operative findings. Elements studied were those
      used in the Capellades classification: height of the iliocaval junction (high,
      very high, low, very low), position of the common iliac vein (lateral,
      intermediate, medial), angle formed by the two common iliac veins. RESULTS: The
      lateral position was the most frequent (31.5%). The average junction angle was 65
      degrees). The only position where it was not possible to "pass" under the
      iliocaval junction was for a very low medial localization with a narrow angle (45
      degrees). DISCUSSION: Our series included a homogenous group comparable with
      other series in the literature. The junction angle for very low medial
      localizations is of considerable importance because it is impossible to fit the
      implant in the L5-S1 under the iliocaval junction if the angle is over 60
      degrees. CONCLUSION: The position of the iliocaval junction, and particularly its
      angle, are of considerable importance for insertion of an L5-S1 disc prosthesis.
      The preoperative angio-MRI provides information on the potential difficulty of
      the insertion. In addition, with this preoperative information, the patient can
      be warned that it may not be possible to insert the implant so that a therapeutic
      alternative may be proposed.

PMID- 16800067
TI  - [Metal-metal-backed polyethylene cemented hip arthroplasty: mid-term results].
AB  - PURPOSE OF THE STUDY: Metal-on-metal bearings in total hip arthroplasty may, in
      theory, provide an effective answer to osteolysis in active patients. The purpose
      of this retrospective study was to evaluate the results of a consecutive series
      of Metasul total hip arthroplasties with a cemented socket. MATERIAL AND METHODS:
      The series was composed of 28 total hip arthroplasties in 23 patients (13 women
      and 10 men). The mean age at operation was 44 +/- 8.3 years (range 22-59 years).
      The initial diagnosis was osteoarthritis (14 hips), osteonecrosis of the femoral
      head (11 hips) and rheumatoid arthritis (3 hips). Cemented cups with a metal
      articulation surface molded into the polyethylene were used. The cup was
      articulated with a 28-mm metallic head. Cemented stems were used in 27 hips,
      whereas a hydroxyapatite coated stem was implanted in one hip. RESULTS: One hip
      required revision for deep infection five months postoperatively. One patient
      (one hip) was lost to follow-up. Twenty-six hips were evaluated at an average 31
      month follow-up (range 12-47 months). All hips were rated excellent or very good.
      Radiographically, seven hips (27%) had a progressive acetabular radiolucent line,
      including three complete radiolucent lines. The latter always were located at the
      bone-cement interface. No implant migration was noted. In these cases, the mean
      socket diameter was lower than for the rest of the cohort (p < 0.001). DISCUSSION
      AND CONCLUSION: Progression of acetabular radiolucent lines remains of concern in
      this series of Metasul artificial hips. It is hypothesized that the diminution of
      polyethylene thickness has led to an increased rigidity of the socket, resulting
      in a higher rate of constraints at the bone-cement interface. Special attention
      must be given to these hips.

PMID- 16800068
TI  - [Femoral revision using cemented stem and compacted bone graft: femoral migration
      analysis].
AB  - PURPOSE OF THE STUDY: If the bone loss is significant, revision total hip
      arthroplasty can be most difficult. We present a series of 30 patients with major
      loss of bone stock treated with the X-change (Exeter) technique for revision
      total hip arthroplasty. MATERIAL AND METHODS: This prospective consecutive series
      included 30 reconstructions performed between 1996 and 2001. Compacted grafts
      with cryopreserved bone were used. Mean follow-up was 42 months (range 24-80).
      According to the SOFCOT classification, bone loss was stage II in one patient,
      stage III in 14 and stage IV in 15. The technique described by Gie, Linder and
      Ling was rigorously applied: smooth stem, no force on the Merckel, cement in the
      impacted allograft, filling of femoral bone defects. Reinforcement with plates,
      mesh, or wire was used as necessary to bridge cortical defects. The Postel-Merle
      d'Aubigne (PMA) score was used to assess clinical outcome. Digital x-rays were
      obtained before and after surgery and at last follow-up to assess implant
      position (vertical migration and frontal deviation), changes in bone stock, and
      the Pierchon classification. Thirty patients were seen at two years follow-up.
      Two patients were lost to follow-up after two years. Material had to be removed
      in two patients because of mechanical intolerance. There was one postoperative
      fracture at six months. One patient died more than two years after implantation.
      The PMA score improved from 11 to 17 at last follow-up. Radiographic results
      showed mean 7.3 mm stem migration and mean 2 degrees frontal deviation which were
      not correlated with clinical presentation. The Pierchon classification revealed
      20 situations of corticalization and eight of trabeculation. Factors affecting
      migration were modalities of graft preparation and time to first weight bearing.
      Migration was unchanged after twelve months. DISCUSSION AND CONCLUSION: The
      functional and radiographic results remained satisfactory in light of the initial
      bone loss. Implant migration did not affect outcome. We have modified the
      surgical technique in line with these results, particularly concerning
      preparation of the impacted bone graft. This technique has the advantage of
      filling bone defects and avoiding therapeutic escalation.

PMID- 16800069
TI  - [Femoral shaft bowing in valgus knees: an anatomic study].
AB  - PURPOSE OF THE STUDY: In a previous anatomic study of healthy knees, we observed
      that femoral valgus cannot be attributed to hypoplasia of the lateral femoral
      condyle. In the present study, in an attempt to determine the site of the femoral
      deformation, we examined femoral shaft bowing in the frontal plan. MATERIAL AND
      METHODS: This cadaver study included 41 lower limbs of healthy Caucasian subjects
      aged over 65 years. The following anatomic landmarks were identified: center of
      the femoral head (H), center of the intercondylar notch (K), center of the talar
      dome (A), center of the femoral shaft half way between the apex of the greater
      trochanter and the middle of the intercondylar notch (S), the tangent line of the
      femoral condyles (I). Three angles were analyzed: HKA, HKI and SKI. There were 23
      normal knees (HKA = 179.1 +/- 1.6 degrees) and 18 valgus knees (HKA = 182.7 +/-
      0.8 degrees). Skeletal analysis (the skeleton of an object being defined as the
      median points of the object) was used to describe the morphology of the femoral
      shaft then to shape it with a second degree function (y = fx2 + bx + c). The
      protocol was repeated seven times to achieve accurate measurement. Accuracy was 1
      degrees for the HKA angle and 0.45 degrees for the HKI and SKI angles. This
      accuracy was comparable to that reported in the literature. The Mann and Whitney
      U test was used to compare means. Spearman's t test was used to search for
      correlations. The first order risk was set at 0.05. RESULTS: The HKI angle of
      valgus knees (95.5 +/- 1.1 degrees) was greater than for the normally aligned
      knees (93.6 +/- 2.4 degrees), confirming the femoral origin of the valgus. The
      form parameter f for the normal knees (1.33 10(-5) +/- 1.41 10(-5)) was greater
      than for the valgus knees (5.71 10(-6) +/- 5.27 10(-6)). There was a correlation
      between the form parameter f and the HKI angle for valgus knees, reflecting a
      relationship between frontal bowing of the femoral shaft and femoral valgus in
      this group. DISCUSSION: The difference observed between the two groups of knees
      regarding the form parameter f and the correlation between f and the HKI angle in
      the valgus knees led us to consider that a considerable part of constitutional
      valgus knees can be attributed to the femoral shaft. Thus for equivalent anatomic
      valgus (SKI), minimal bowing (f) of the femoral shaft in valgus knees leads to
      greater mechanical valgus (HKI). These results confirm those obtained in our
      earlier study where we concluded that hypoplasia of the lateral femoral condyle
      does not contribute to constitutional valgus knees. We hypothesize that the same
      could be true for degenerative disease of constitutional valgus knees. For
      surgical cure, the origin of the misalignment in valgus knees dictates the
      rotation position of the femoral component of total knee arthroplasty and the
      lengthening technique for the lateral structures.

PMID- 16800070
TI  - [Intra- and postoperative fractures of the femur in total knee arthroplasty: risk
      factors in 32 cases].
AB  - PURPOSE OF THE STUDY: We reviewed fractures of the distal femur occurring during
      or after total knee arthroplasty in order to identify risk factors. MATERIAL AND
      METHODS: Twelve intraoperative fractures occurred between 1990 and 2000 among 617
      total knee arthroplasties performed during this period. The circumstances of
      these fractures were noted in comparison with other prosthetic implants. Twenty
      other fractures of the distal femur occurred in 20 patients who had had a total
      knee arthroplasty during the same time period. Mean patient age at surgery was 72
      years (range 69-77). In addition to demographic data, we noted risk factors: bone
      demineralization related to general condition, rheumatoid arthritis or
      corticosteroid therapy, trochlear notch prior to the trochlear cut, bone
      resorption under the femoral implant, repeated knee surgery, abnormal stress on
      the distal femur due to hip disease, periprosthetic osteolysis without loosening
      related to polyethylene debris or metallosis, loosening, type of prosthesis, loss
      of bone stock because of the femoral implant, life of prosthesis. RESULTS:
      Intraoperative fractures usually occurred in specific circumstances: use of a
      posterior stabilized prosthesis, probably with insufficient preparation and
      position of the stabilization element, probably excessive impaction in
      osteoporotic bone (rheumatoid arthritis), difficult exposure (arthroplasty after
      prior osteotomy), fracture starting from the separator passing over the posterior
      aspect of the tibia and reaching the intercondylar notch. Independently of these
      intercondylar fractures, supracondylar or diaphyseal fractures were essentially
      observed for revision prostheses using a femoral stem. Postoperative fractures
      were observed in patients who had prior surgery of the distal femur (revision of
      femoral osteotomy, fracture of the distal femur, arthrodesis), in patients with
      significant loss of bone stock (posterior stabilized prosthesis), or poor bone
      quality (rheumatoid arthritis), and in elderly patients with neurological
      impairment and frequent falls. The trochlear notch did not appear to be
      sufficient to be the only cause of fracture but was nevertheless an element
      frequently associated with other risk factors. DISCUSSION AND CONCLUSION: This
      study shows that fracture of the distal femur occurs in certain preferential
      circumstances. Considering these elements, a certain number of preventive
      measures can be discussed for technical modifications or choice of implants.

PMID- 16800071
TI  - [Treatment of fractures of the distal femur on total knee arthroplasty].
AB  - PURPOSE OF THE STUDY: Fractures of the distal femur near a total knee
      arthroplasty are usually observed in patients aged over 70 years victims of low
      energy trauma. The rate of complications is high: in the literature 25-75 %, even
      when treated by experienced surgeons. The purpose of this study was to detail
      therapeutic modalities used for the treatment of these fractures with their
      advantages and disadvantages and to determine the morbidity of complications
      which do occur. MATERIAL AND METHODS: Twenty distal fracture of the femur were
      treated between 1990 and 2000 in twenty patients who had a total knee
      arthroplasty. Mean patient age at surgery was 72 years (range 69-77). The
      fracture was a short oblique fracture in four, transversal in five, long and
      spiral in four and comminuted in the others. In four fractures, the preoperative
      radiographic analysis suggested concomitant loosening. Therapeutic modalities
      included suspension traction for two, femorotibial external fixation for two.
      Retrograde nailing was possible in two patients. Fixation with a screw plate or a
      blade plate was used for nine fractures. The prosthesis was revised
      systematically if loosening was observed. This was done in three cases with
      preservation of the tibial piece and in two cases, changing the complete
      prosthesis, using a long femoral stem in all. RESULTS: Mean follow-up was two to
      ten years. Immediate weight bearing was possible for four of the five patients
      for whom only the femoral piece was changed with a long stem. For the others,
      weight bearing was deferred until fracture healing was obtained after a mean five
      months (range 4-42). Bone healing required one, or two, revisions in three
      patients. Three patients died within one year of their fracture of the distal
      femur. There were no cases of infection or late healing. At last follow-up, the
      knee and function score regressed after treatment of the fracture. The two scores
      dropped 20 points compared with the pre-operative score (78 +/- 15 to 56 +/- 19
      for the knee score and 72 +/- 16 to 54 +/- 18 for the function score). The knee
      score fell because of difficulty going up and down stairs and use of crutches.
      Treatments which stiffened the knee were traction suspension and external
      fixation. Loss of joint motion was about the same with or without prosthesis
      revision. The tibiofemoral angle measured before the fractures (postoperative
      goniometry) then after fracture healing or after changing the femoral prosthesis,
      showed an alignment of 183 degrees before the fracture and 178 degrees after
      healing or revision of the femoral piece. Three patients experienced another
      fracture of the same femur after healing of the initial fracture or after
      changing the knee prosthesis. DISCUSSION: Fracture of the distal femur on a total
      knee prosthesis is a serious complications because of the mortality and the
      difficulty in achieving functional recovery after treatment. Therapeutic
      difficulties involve the type of skin incision, the position of the screws in
      relation to the femoral component, the possible need for bone graft, and finally
      the requirement to change the femoral piece with a centro-medullary stem.

PMID- 16800072
TI  - [Tillaux fractures in teenagers: a review of nineteen cases].
AB  - PURPOSE OF THE STUDY: Tillaux fractures in adolescents correspond to Salter and
      Harris type III fractures involving the anterolateral portion of the tibial
      epiphysis. These are intra-articular fractures. The objective was to determine
      the circumstances of these fractures, the radiological signs, and the therapeutic
      modalities as well as the long-term clinical and radiological outcome. MATERIAL
      AND METHODS: We reviewed 19 Tillaux fractures. Ten patients underwent surgical
      treatment and nine orthopedic treatment following importance of displacement.
      RESULTS: At mean follow-up of 33.8 months, results were rated good in 17 on 19
      cases. DISCUSSION: This fracture is often observed in teenagers victims of trauma
      with external rotation of the foot. Closure of distal growth cartilage of the
      tibia occurs medially to laterally, the anterolateral portion remaining open
      longer. Forced external rotation of the anterior tibiofibular ligament pulls off
      an anterolateral fragment of the distal tibial epiphysis. Surgical treatment is
      indicated for fractures with a displacement of more than 2 mm or a vertical
      displacement to achieve open reduction and screw fixation. Orthopedic treatment
      is used for non-displaced fractures. CONCLUSION: The prognosis of Tillaux
      fractures is good as was observed in our series and in series reported in the
      literature.

PMID- 16800073
TI  - [Optimal management of patients with stress fractures and the role of the
      orthopedic surgeon in reducing the risk of new fractures].

PMID- 16800074
TI  - [Congenital club foot: treatment in childhood, outcome and problems in
      adulthood].
AB  - PURPOSE OF THE SYMPOSIUM: Treatment of idiopathic talipes varus, or congenital
      clubfoot, is designed to re-align the foot to alleviate pain and allow
      plantigrade weight bearing with adequate joint motion despite the subnormal
      radiographic presentation. This symposium was held to review current management
      practices for congenital clubfoot in children and to analyze outcome in adults in
      order to propose the most appropriate therapeutic solutions. MANAGEMENT OF
      CONGENITAL CLUBFOOT IN CHILDREN: Idiopathic talipes varus can be suspected from
      the fetal ultrasound. Parents should be given precise information concerning
      proposed treatment after birth. Deviations must be assessed in the newborn then
      revised regularly using objective scales during and after the end of treatment.
      This enables a better apprehension of the evolution in comparison with the
      severity of the initial deformation. Conservative treatment is proposed by many
      teams: a functional approach (rehabilitation and minimal use of orthetic
      material) or the Ponseti method (progressive correction using casts associated
      with percutaneous tenotomy of the calcaneal tendon) are currently preferred. If
      such methods are insufficient or unsuccessful, surgery may be performed as needed
      at about 8 to 11 months to achieve posteromedial release. Good results are
      obtained in 80% of patients who generally present minimal residual deformations
      (adduction of the forefoot, minimal calcaneal varus, residual medial rotation,
      limitation of dorsal flexion), which must be followed regularly through growth.
      The difficulty is to distinguish acceptable from non-acceptable deformation. At
      the end of the growth phase, severe articular sequelae are rare (stiff joint,
      recurrence of initial deformation, overcorrection) but difficult to correct
      surgically: osteotomy, tendon transfer, double arthrodesis, Ilizarov fixator.
      Gait analysis is essential to quantify function and obtain an objective
      assessment of the impact on higher joints, providing valuable guidance for
      surgical correction. OUTCOME IN ADULTHOOD: There have been very few studies
      evaluating the long-term functional outcome after treatment during childhood.
      According to two studies presented at this symposium (Brussels, Lausanne),
      results have been generally good but with subnormal radiographs irrespective of
      the type of treatment or how early treatment started in childhood. Hypoplasia of
      the talar dome is a constant finding and is correlated with limitation of dorsal
      flexion of the ankle joint. A small degree under-correction is often observed but
      well tolerated while overcorrection is generally less well tolerated. Functional
      outcome depends highly on preservation of subtalar joint motion. There have been
      no reports on the results of treatment of sequelae in adults. Most problems
      (pain, stiffness, osteoarthritis) are observed in the mid or rear foot.
      Indications for conservative surgery (osteotomy) of the mid or rear foot are rare
      compared with indications for combined arthrodesis. Talocrural decompensation is
      a turning point observed in the adult. Management at this point is difficult:
      fusion of the ankle worsens the situation by increasing the stress on the
      forefoot and aggravating the disability; implantation of an ankle prosthesis is
      technically difficult and remains to be fully developed. Treatment of the dorsal
      bunion of the great toe may require tendon transfer and/or fusion. CONCLUSION: A
      child born with clubfoot will never have a normal foot in adulthood. Sequelae
      present at the end of growth will intensify during adult life; under-correction
      is easier to treat in adulthood than overcorrection. The most difficult problems
      in adulthood are: neglected clubfoot, over correction, and degradation of the
      talocrural joint.

PMID- 16800075
TI  - [Mini-invasive implantation of an uni-compartmental medial knee prosthesis].

PMID- 16800076
TI  - [Value of brain imaging in assessment of cognitive symptoms. Cognitive and
      emotional impact of antipsychotic drug treatment]].

PMID- 16800077
TI  - [Neurobiology in the neuropharmacology of antipsychotic drugs].

PMID- 16800078
TI  - [Pharmacology of antipsychotic drugs]].

PMID- 16800079
TI  - [Quotidien prescription: between references and reality].

PMID- 16800080
TI  - [Managing agitation in acute psychotic episodes of schizophrenia].

PMID- 16800081
TI  - [Current stakes in managing patients with schizophrenia].

PMID- 16800082
TI  - [Cognitive disorders and psychosocial rehabilitation in schizophrenia].

PMID- 16800083
TI  - [The mechanism of liver fibrosis become clearer. Drugs against the fibrotic
      process coming].

PMID- 16800084
TI  - [Lhx2 seems to inhibit the development of liver cirrhosis. Gene discovery makes
      the development of drugs against this enormous health problem possible].

PMID- 16800085
TI  - [Delayed sleep phase. Unknown, common and curable].

PMID- 16800086
TI  - [Work environment of anesthetists can be improved. Final report from a work
      environment project].

PMID- 16800087
TI  - [Quality-labelled specialist with 360-degree assessment. Several colleagues'
      evaluations of different kinds of competence are considered for an assessment].

PMID- 16800088
TI  - [Venous blood sample collection and handling errors can affect test results. A
      questionnaire study of pre-analytical factors at a somatic hospital ward].

PMID- 16800089
TI  - [Nasal obstruction].

PMID- 16800090
TI  - [Do breast milk and cow's milk hydrolysate protect against cow milk allergy or
      allergic disease?].

PMID- 16800091
TI  - [The role of politics in the successful fight against AIDS in Uganda].

PMID- 16800092
TI  - [Cervix cancer prevention--achieved success must be surpassed].

PMID- 16800093
TI  - [Endovascular treatment better than open surgery for many patients with abdominal
      aorta aneurysm].

PMID- 16800094
TI  - [The correct name is eczema!].

PMID- 16800095
TI  - [Prominent artist a dreaded serial killer?].

PMID- 16800096
TI  - Plant stanol and sterol esters in prevention of cardiovascular diseases: a
      review.
AB  - Plant sterol and stanol esters have been introduced as an additional dietary
      means to lower serum total and LDL cholesterol concentration. In short-term
      studies they lower LDL cholesterol by 10%, and according to a meta-analysis by
      Malcolm Law the incidence of coronary heart disease is considered to be reduced
      by over 20% in long-term use of these products. Plant stanol and sterol esters
      are not identical sterols; they have different metabolic effects and their long
      term efficacy seems to be different. The present review deals with the
      differences of the sterols and discusses what is known of their role in
      preventing the cardiovascular diseases.

PMID- 16800097
TI  - Effect of long-term atorvastatin treatment on the electrophysiological and
      mechanical functions of muscle.
AB  - OBJECTIVE: To study alterations in muscle function combining physiological,
      electrophysiological and metabolic measurements in patients receiving a statin at
      various dosages during long-term therapy. MATERIAL: A 3-month (D0, D30 and D90)
      longitudinal physiological and electrophysiological muscle study was performed in
      26 patients receiving 10, 40 or 80 mg/day atorvastatin. METHOD: All subjects
      performed maximal (MVC) and submaximal (60% MVC) isometric thumb adduction,
      handgrip and knee extension exercises during the recording of surface
      electromyograms (EMG) of the adductor pollicis (AP), flexor digitorum (FD) and
      vastus lateralis (VL). The compound muscle potential (M-wave) evoked by direct
      muscle stimulation was measured at rest and after 60% MVCs and the EMG power
      spectrum was analyzed during sustained effort. Blood was sampled from an
      antecubital vein for measurements of pH, lactate and potassium levels after thumb
      adduction and handgrip exercises. The measurements were repeated on Day 0 (D0),
      D30 and D90. RESULTS: Atorvastatin did not affect the MVC and endurance time to
      fatigue. Post-exercise M-wave alterations in the AP began at D30 with the 80
      mg/day treatment and there was a reduced or suppressed leftward shift in the EMG
      power spectrum in the AP and VL with all 3 dosages. In the AP, the EMG changes
      appeared earlier (D30) with 80 mg/day whereas they only occurred at D90 on the
      lower dosages. Atorvastatin had no effect on the maximal postexercise variations
      in pHv and lactate but it significantly reduced the maximal increase in plasma
      potassium concentration after thumb adduction and handgrip exercise, the effects
      being only present at D90 on 10 mg/day but occurring as early as D30 with higher
      dosages. CONCLUSION: A 3-month atorvastatin treatment did not affect the maximal
      performance of skeletal muscle during voluntary efforts but EMG analysis revealed
      a reduced muscle excitability and an attenuated adaptation to fatigue. These
      effects prevailed in muscles containing the largest proportion of slow-oxidative
      fibers and were associated with a reduced outward flow of potassium.

PMID- 16800098
TI  - Do intensive care patients need an individualized dosing regimen for
      levofloxacin?
AB  - OBJECTIVE: In general, the pharmacokinetics (PK) of antibiotics in intensive care
      unit (ICU) patients are known to differ from healthy subjects. These differences
      can pose challenges in developing appropriate dosing guidelines. The primary
      objective of this report was to characterize the disposition of levofloxacin in
      critically ill patients and to assess any relationships between patient
      covariates and the PK parameters. METHODS: 20 patients in the ICU were given
      levofloxacin, 500 mg, as an i.v. infusion for a half hour. Plasma samples were
      taken until 24 hours and assayed using HPLC. The concentration-time data were
      analyzed using population analysis with NONMEM. RESULTS: The data were described
      using a 2-compartment model. Creatinine clearance was determined to be a
      statistically significant predictor of variability in total levofloxacin
      clearance. For patients with higher levofloxacin clearance, the resulting
      efficacy for different strains of bacteria (expressed as free AUC/MIC ratios)
      suggested that for less sensitive pathogens, a dosage adjustment may be needed.
      CONCLUSION: A model describing the pharmacokinetics of levofloxacin in critically
      ill patients was developed. It was determined that creatinine clearance has a
      significant role in the disposition of levofloxacin. This may have significant
      implications in the clinical setting for identifying optimal dosage regimens for
      ICU patients.

PMID- 16800099
TI  - The diffusion of nimesulide gel into synovial fluid: a comparison between
      administration routes.
AB  - BACKGROUND: Nimesulide is available in gel formulation and applied mainly for
      topical pain management. However, its passage to the synovial fluid is not yet
      clear. The aim of this study was to evaluate if topical administered nimesulide
      passes into the synovial fluid and to compare its concentration with the oral
      nimesulide administration regimen. METHODS: Synovia and plasma nimesulide
      concentrations were investigated in patients after topical (Sulidin gel 1%) and
      oral (Mesulid tablet) drug administration. 34 adult outpatients who were
      scheduled to have an arthroscopic knee examination for mainly meniscal tears
      repair and who had knee pain during this period were enrolled in the first part
      of the study. One group received topical nimesulide gel to the skin of the knee
      whereas the second group received oral 2 x 100 mg nimesulide tablets, 4-7 days
      before the planned arthroscopy. Synovial fluid and plasma samples were taken
      simultaneously during the arthroscopy and analyzed using HPLC. In addition, an
      open-label pilot study was performed to investigate the efficacy and safety of 1
      week administration of nimesulide gel. 63 knee osteoarthritis patients were asked
      to complete the WOMAC Osteoarthritis Index questionnaire before and 1 week after
      use of Sulidin gel applied 3 times daily. RESULTS: Synovia and plasma nimesulide
      concentrations were 19.7 +/- 8.6, 11.8 +/- 3.0 and 1958.8 +/- 397.5, 3631.9 +/-
      799.3 ng/ ml for topical and oral administration groups, respectively. There was
      a significant (paired Student's t-test) improvement after 1 week nimesulide
      treatment in all WOMAC Osteoarthritis Index parameters measured. CONCLUSION:
      Nimesulide passes into the synovial fluid after topical administration and may
      have potential benefits in knee osteoarthritis treatment. The actual efficacy and
      safety of topical nimesulide gel administration should be investigated in a long
      term, randomized, placebo-controlled clinical trial.

PMID- 16800100
TI  - Nevirapine/lamivudine/stavudine as a combined-formulation tablet: bioequivalence
      study compared with each component administered concurrently under fasting
      condition.
AB  - OBJECTIVE: The objective of the study was to compare the bioequivalence of a
      fixed-dose combination of a nevirapine 200 mg, lamivudine 150 mg and stavudine 30
      mg combination tablet with application of the 3 medications, at the same dosage,
      concurrently as separate formulations, in healthy, adult subjects under fasting
      conditions. MATERIAL AND METHODS: An open-label, balanced, randomized, 2
      treatment, 2-period, 2-sequence, single-dose, crossover bioavailability study was
      conducted in 40 subjects with 21-day washout period between each treatment. Blood
      samples were collected for 168 hours. Plasma concentrations of nevirapine,
      lamivudine and stavudine were determined using a validated LC-MS-MS method.
      Noncompartmental pharmacokinetics and statistical analyses were performed using
      SAS (SAS Institute Inc., Cary, NC, USA) software (SAS System under Windows,
      Version 8.02). RESULTS: The ratios of least-square means and the 90% confidence
      intervals of the log-transformed data were calculated for AUC(0-t), AUC(0-inf),
      and Cmax. The 90% confidence interval for least-square mean ratio between test
      and reference formulation for log-transformed parameters Cmax, AUC(0-t) and AUC(0
      inf) were within the requirements of the 80-125% range. CONCLUSION: The test
      formulation (Ranbaxy Laboratories Ltd., Gurgaon, India) is bioequivalent to the
      reference formulations both in terms of rate and extent of absorption after
      single-dose administration under fasting condition.

PMID- 16800101
TI  - Bioequivalence of abacavir generic and innovator formulations under fasting and
      fed conditions.
AB  - OBJECTIVE: Abacavir sulfate is a synthetic carbocyclic nucleoside analogue
      indicated for the treatment of HIV-1 infection in combination with other
      antiretroviral agents. The objective of the current study was to determine the
      bioequivalence between a generic formulation of abacavir and the innovator
      product. MATERIAL AND METHODS: A total of 80 subjects were randomly assigned to
      receive a single 300 mg oral dose of abacavir sulfate as the generic (Ranbaxy
      Abacavir, Ranbaxy Laboratories Ltd., equivalent to 300 mg of abacavir) and
      innovator (Ziagen, GlaxoSmithKline) tablet formulations in 2-way crossover
      studies performed under fasting (n=40) and fed (n=40) conditions. Multiple blood
      samples were collected over 14 hours and plasma concentrations of abacavir were
      assayed using an LC/MS/MS method with a limit of quantitation of 25.0 ng/ml.
      Pharmacokinetic (PK) parameters were calculated using noncompartmental methods.
      RESULTS: Under fasting conditions, geometric mean area under the curve from time
      0 to the last measurable concentration (AUC(0-t)), area under the curve
      extrapolated to infinity (AUC(0-infinity) and maximum plasma concentrations
      (Cmax) of abacavir for the generic (5565 ng x h/ml, 5668 ng x h/ml and 2526
      ng/ml, respectively) and innovator (5675 ng x h/ml, 5770 ng x h/ml and 2528
      ng/ml, respectively) products were very similar. Under fed conditions, mean
      values of AUC(0-t) AUC(0-infinity) and Cmax for the generic (4487 ng x h/ml, 4571
      ng x h/ml and 1841 ng/ml, respectively) and innovator (4574 ng x h/ml, 4654 ng x
      h/ml and 1781 ng/ml, respectively) formulations were also very similar. Ratios of
      LSM and 90% confidence intervals of PK parameters between the 2 formulations were
      within 80.0 - 125.0% under fasting and fed conditions, suggesting that the 2
      tablet formulations resulted in similar rate and extent of bioavailability.
      Adverse events for the generic and innovator products were similar in nature and
      frequency in the fasting and fed studies. CONCLUSIONS Based on the above results,
      the generic tablet formulation of abacavir developed by Ranbaxy should be equally
      effective as the innovator product.

PMID- 16800102
TI  - Pharmacokinetic simulations and AUC: center specificity in the limited sampling
      model.

PMID- 16800103
TI  - [What a job!].

PMID- 16800104
TI  - [The goal is not to "punish" adolescents, but to avoid their marginalization].

PMID- 16800105
TI  - [The June 27 1990 Law: toward the project of the reform?].

PMID- 16800106
TI  - [The creation of mutual aid group].

PMID- 16800107
TI  - [Entering into a contact with a patient].

PMID- 16800108
TI  - [A subtle blend of flesh and body].

PMID- 16800109
TI  - [The voyage into the land of public health].

PMID- 16800110
TI  - [The sector in question... and some questions about the sector].

PMID- 16800111
TI  - [Psychiatric sector: practice and morals].

PMID- 16800112
TI  - [The influence of the political sector on the identity of public health care].

PMID- 16800113
TI  - [Stakes in clinical psychiatry stemming from an experience of the sector].

PMID- 16800114
TI  - [Psychiatric follow-up services: between specialization in Hospital 2007].

PMID- 16800115
TI  - [Specialization and community means].

PMID- 16800116
TI  - [Indispensable relations].

PMID- 16800117
TI  - [Diogenes: mental health care team and preventive care].

PMID- 16800118
TI  - Molecular systematics, phylogeny and ecology of anisakid nematodes of the genus
      Anisakis Dujardin, 1845: an update.
AB  - Advances in the taxonomy and ecological aspects concerning geographical
      distribution and hosts of the so far genetically recognised nine taxa of the
      nematodes belonging to genus Anisakis (i.e. A. pegreffii, A. simplex s.s., A.
      simplex C, A. typica, A. ziphidarum, Anisakis sp., A. physeteris, A.
      brevispiculata and A. paggiae) are here summarized. Genetic differentiation and
      phylogenetic relationships inferred from allozyme (20 enzyme-loci) and
      mitochondrial (sequences of cox-2 gene) markers, are revised and compared. The
      two genetic analyses are congruent in depicting their phylogenetic relationships.
      Two main clusters are showed to exist in the obtained trees, one encompassing the
      species A. pegreffii, A. simplex s.s., A. simplex C, A. typica, A. ziphidarum and
      Anisakis sp.; while, the second including A. physeteris, A. brevispiculata and A.
      paggiae. The existence of two clades is also supported by their morphological
      differentiation in adult and larval morphology. Comparison of phylogenetic
      relationships among Anisakis spp. with those currently available for their
      cetacean definitive hosts suggests parallelism between host and parasite
      phylogenetic tree topologies. Preliminary data for reconstruction of a possible
      co-evolutionary scenario between cetacean hosts and their Anisakis endoparasites
      suggests that cospeciation and host-switching events may have accompanied the
      evolution of this group of parasites. Finally, genetic/molecular markers for the
      identification of the so far genetically recognized taxa of Anisakis at any life
      stage and both sexes were given also in relation to human anisakiosis is
      discussed.

PMID- 16800119
TI  - Three new species of the genus Oswaldocruzia Travassos, 1917 (Nematoda,
      Trichostrongylina, Molineoidea) parasites of Enyalius spp. (Iguanidae) from
      Brazil.
AB  - Three new species of the genus Oswaldocruzia Travassos, 1917 belonging to the sub
      family Molineinae are described from the stomach and/or the small intestine of
      Enyalius spp. from Brazil. They belong to group 6 of Ben Slimane, Chabaud &
      Durette-Desset (1996). In this group they share along with O. peruensis Ben
      Slimane, Verhaag & Durette-Desset, 1995, a parasite of Iguanidae from Peru the
      followings linked characters: (i) a caudal bursa of type II; (ii) cervical alae
      present; (iii) undulated cuticular ridges. The Peruvian species differs from the
      Brasilian species by the absence of a strut in the cervical alae, by a small
      number of cuticular ridges at mid-body and by a spicular fork with a ramified
      inner twig. Oswaldocruzio fredi n. sp., a parasite of the stomach and the small
      intestine of Enyalius iheringii, mainly differs from the two other species by the
      absence of the oesophageal ventral cuticular ridges. Oswaldocruzia benslimanei n.
      sp., a parasite of the small intestine of Enyalius bilineatus, differs from
      Oswoldocruzia burseyi n. sp., a parasite of the stomach of Enyalius perditus, by
      the division of the fork at 23.4 % of spicule length (versus 32 %), and the
      length of the blade longer than the fork. Oswoldocruzia subauricularis sensu
      Freitas, 1955 nec Rudolphi, 1819 and O. mazzai sensu Vicente, 1981 nec Travassos,
      1935 should be considered as species inquirendae.

PMID- 16800120
TI  - The infective larva of Litomosoides yutajensis Guerrero et al., 2003 (Nematoda:
      Onchocercidae), a Wolbachia-free filaria from bat.
AB  - The infective larva of Litomosoides yutajensis Guerrero et al., 2003, a parasite
      of the bat Pteronotus pamellii, is described; it is distinct from congeneric
      infective larvae by the absence of caudal lappets. The life cycles of five other
      species of Litomosoides are known; three are parasites of rodents, one of a
      marsupial and one of a bat. As with these species, the experimental vector of L.
      yutoajensis used was the macronyssid mite Ornithonyssus bacoti. In nature, the
      main vectors are probably other macronyssids but transmission by O. bacoti, with
      its large host-range, could account for the characteristic host-switchings in the
      evolution of Litomosoides. Unlike the murine model L. sigmodontis Chandler, 1931,
      L. yutajensis is devoid of the endosymbiontic bacteria Wolbachia and may be of
      great interest.

PMID- 16800121
TI  - Genetic differences between Tunisian camel and sheep strains of the cestode
      Echinococcus granulosus revealed by SSCP.
AB  - Ovine and dromedary Echinococcus granulosus isolates from Tunisia were identified
      as G1 and G6 strains based on polymorphism of the mitochondrial cytochrome C
      oxydase CO1. Single strand conformation polymorphism (SSCP) was used in order to
      examine the genetic variation within and between Tunisian G1 and G6 strains and
      to estimate the extent of selfing. The dromedary isolates are genetically
      distinct from sheep isolates (high value of genetic variation between
      populations: Fst= 0.46). No significant deficiency in heterozygotes was found in
      sheep isolates, whereas heterozygote deficiency (suggesting selfing) was found in
      a limited number of camel isolates.

PMID- 16800122
TI  - Myxobolus cuneus n. sp. (Myxosporea) infecting the connective tissue of Piaractus
      mesopotamicus (Pisces: Characidae) in Brazil: histopathology and ultrastructure.
AB  - The characteristics of Myxobolus cuneus n. sp. and its relationship to the host
      Piaractus mesopotamicus are described based on light and electron microscopy and
      histological observations. Polysporic plasmodia measuring 20 microm to 2.1 mm in
      size were found in 63.3 % of the P. mesopotamicus examined. The parasite was
      found in the gall bladder, urinary bladder, gills, spleen, fins, head surface,
      liver and heart. Generative cells and disporoblastic pansporoblasts occurred
      along the periphery of the plasmodia, and mature spores were found in the
      internal region. The mature spores had a pear shaped body in frontal view, with a
      total length of 10.0 +/- 0.6 microm and a width of 5.1 +/- 0.3 microm (mean +/-
      SD). The spore wall was smooth with sutural folds. The polar capsules were
      elongated, were pear shaped, and equal in size (length 5.7 +/- 03 microm; width
      1.7 +/- 0.2 microm), with the anterior ends close to each other. The polar
      filaments were tightly coiled in 8-9 turns perpendicular to the axis of the
      capsule. The plasmodia were always found in connective tissue (wall of the
      arterioles of the gill filaments, serous capsule of the gall bladder, middle
      layer and subepithelial connective tissue of the urinary bladder, connective
      tissue between the rays of the fins, subcutaneous tissue of the head surface and
      fibrous capsule spleen). The parasite caused important damage in the gills, where
      development occurred in the wall of gill filament arterioles; a mild macrophage
      infiltrate was also observed. In advanced developmental stages, the plasmodia
      caused deformation of the arteriole structure, with a reduction and, in some
      cases, obstruction of the lumen. The parasite was found throughout the period
      studied and its prevalence was unaffected by host size, season or water
      properties.

PMID- 16800123
TI  - Characterization of Toxoplasma gondii from domestic animals from Minas Gerais,
      Brazil.
AB  - In an attempt to isolate and characterize Toxoplasma gondii from the State of
      Minas Gerais, Brazil, musculature samples from 72 pigs, 25 dogs, 28 free-range
      chickens and 50 chickens produced in industrialized farms were collected.
      Antibodies to T. gondii have not been detected in pigs, but were found in nine
      (40.9 %) out of 22 dogs, and in 15 (53.6 %) of 28 free range chickens. T. gondii
      was not isolated from pigs and industrialized chickens, but from eight dogs and
      11 free range chickens. In order to determine T. gondii virulence, female BALB/c
      mice were inoculated with 10(3), 10(2), 10(1) and 10(0) tachyzoites of the 19
      isolates. The strains RH (virulent) and ME49 (non-virulent) were used as
      references. Isolates were divided into three groups according to the virulence
      phenotype: five isolates were classified into virulent in mice, one into non
      virulent and 13 into intermediate virulent. Nested-PCR of T. gondii SAG2 locus
      amplified DNA from 21 out of 22 DNA samples directly extracted from heart of free
      range chickens. These samples were genotyped through a PCR-RFLP assay. Seventeen
      (80.9 %) were classified into type I; one (4.8 %) into type III and three (14.3
      %) into type I or II.

PMID- 16800124
TI  - [Chinius barbazani n. sp. from Thailand (Diptera: Psychodidae)].
AB  - A new species of sandfly is described from limestone caves in Thailand. The
      inclusion of this species in the genus Chinius, which up until now was
      monospecific, is discussed. It is justified on the basis of characteristics of
      the head (eyes, pharynx, cibarium, complete interocular suture and length of the
      mouth pieces), thorax (rounded wings), abdomen (presence of trumpet glands on the
      tergites 4 and 5 of the male) and genitalia (morphology of the male genitalia and
      of the spermathecae in the female). Detailed descriptions and drawings are given.
      The wing of C. barbazani n. sp. lacks of vein R2 in both sexes. This anomaly,
      regarding to Phlebotominae, is discussed and considered as a probable
      autapomorphic regression. The differential diagnosis with Chinius junlianensis
      Leng, 1987, rests on a number of characteristics of the wing venation, antennal
      formula and the length of the male and female genital ducts, which are five times
      shorter in C. barbazani n. sp.

PMID- 16800125
TI  - [Some ecological parameters of Ctenocephalides felis strongylus (Jordan, 1925)
      (Siphonaptera: Pulicidae)].
AB  - Among the fleas of medico-veterinary interest, Ctenocephalides felis (Bouche, 1
      835) is the one most studied. This taxon includes two subspecies: Ctenocephalides
      f. felis, and Ctenocephalides f. strongylus (Jordan, 1925); only C. f. felis has
      been the subject of almost all the studies available. We were, thus, interested
      in C. f. strongylus which can be regarded as the species of substitution of C. f.
      felis on the African continent. The purpose of our work was to establish some
      biological parameters such as: hatching of eggs, cycle of development and
      emergence of adults. These data were compared with those available on C. f.
      felis. With temperatures ranging between 19 degrees C and 29 degrees C and a
      relative humidity (HR) of 75 % +/- 5, the hatching rates of eggs observed from
      the two subspecies of C. felis, are higher than 88 %. The optimal temperature of
      eggs hatching for C. felis is 29 degrees C, with more than 70 % of hatching
      obtained in 1-2 days after the laying. The larval developments of the two
      subspecies are almost identical and function of the temperature 18-9 days with 27
      degrees C). Only differs the minimal duration of the progressive cycle. For C. f.
      strongylus, it lasts in 16-17 days at 29 degrees C, 20-21 days at 27 degrees C
      and 38 days at 19 degrees C. For C. f. felis, published values give report of 15
      days at 27 degrees C and 17 days at 24 degrees C. The emergence of adults of C.
      f. strongylus takes eight to ten days between 19 degrees C and 29 degrees C,
      while data published on C. f. felis are about 26 days at 19 degrees C and 15 days
      at 27 degrees C.

PMID- 16800126
TI  - Circulating fibrosis markers, eosinophil cationic protein and eosinophil protein
      X in patients with Wuchereria bancrofti infection: association with clinical
      status.
AB  - We measured the concentrations of several circulating fibrosis markers (type I
      collagen I, type III procollagen, hyaluronan) and eosinophil granule proteins
      (ECP and EPX) in lymphatic filariosis patients to investigate their relationship
      with clinical, parasitological and immunological data. This study was conducted
      in Polynesian patients with various stages of the disease (acute lymphangitis,
      chyluria, hydrocoele, elephantiasis), a closely related microbial lymphangitis
      and endemic controls. We observed modifications of the different markers in this
      pathology. Serum type I collagen and PIIINP were decreased. Serum hyaluronan,
      linked to perilymphatic granulomatous inflammation, was significantly increased
      in acute lymphangitis and elephantiasis patients. Serum ECP was also increased,
      at the limit of significance in our sample, in elephantiasis patients. These two
      last markers, already validated in another helminth disease, schistosomiasis,
      have potential interest in terms of follow-up of morbidity in these parasitic
      diseases.

PMID- 16800127
TI  - [Triatominae and Cactaceae: a risk for the transmission of the American
      trypanosomiasis in the peridomicilary space (Northeast Brazil)].
AB  - Field observations carried in semi-arid Brazil Northeast point out the frequent
      association, in the peridomiciliary space, between a cactus, Cereus jamacaru, the
      occurrence of nests in its branches and the occurrence of two species of insects
      vectors of Trypanosoma cruzi, pathogenic agent of Chagas disease: Rhodnius
      neglectus and Triatoma pseudomaculata. The analysis of the architectural
      variables of this Cactaceae shows that the presence of nests, and thus of
      insects, depends on the traditional practices of management of this cactus. This
      study underlines the relevance of an integrated approach of the ecology of
      Triatominae for the identification of factors of risk.

PMID- 16800129
TI  - [Urologic ultrasonography].

PMID- 16800128
TI  - Leucocytozoon toddi in falcons from Kuwait: epidemiology, clinical signs and
      response to melarsomine.

PMID- 16800130
TI  - [Cost-effectiveness of ultrasound in a urology department].
AB  - Ultrasonography has demonstrated to be a precise test with high sensitivity and
      specificity. The urologist is the most capable professional to obtain the maximum
      effectiveness of this technique, so that the availability of ultrasound machines
      in urology departments rationalizes and limits the demand of ultrasound tests,
      diminishes significantly the indication of radiological tests and the number of
      cystoscopies, being an indispensable element in high-resolution office
      consultations. We report the statistics of the use of ultrasound in our
      department, with the disappearance of the demand of ultrasound tests from the
      urology outpatient clinic to the radiology department. The use rate is high,
      reflecting the functional criteria for use of the ultrasound equipment. In the
      economic analysis we found there is an almost complete absence of controlled
      clinical trials comparing the cost effectiveness of imaging tests in urology.
      There are not cost studies comparing ultrasounds performed by the urologist with
      those performed by radiologists.

PMID- 16800131
TI  - [Ultrasonography for the study of small renal masses].
AB  - OBJECTIVES: To perform an update on the usefulness of ultrasound in the study of
      small size renal tumors and its current possibilities. METHODS: We review the
      results of ultrasound in this pathology with the addition of the most recent
      technological advances such as a harmonic digital converters and power color
      Doppler. We analyze its contribution to the differential diagnosis of the cystic
      pathology, to the definition of solid masses, to the detection and
      characterization of small size masses, and to the definition of the vascular
      patterns of various tumors. RESULTS: Ultrasonography offers a diagnostic safety
      of 98% in cystic masses, being able to detect them from 0.5 cm diameter in
      favourable conditions. The differential diagnosis of multiloculated masses,
      multivesicular hydatid cyst, multiloculated cystic nephroma, and multiloculated
      cystic carcinoma still poses great difficulty, the same way it happens with other
      radiological tests. For solid masses, the greater image resolution has lead to a
      progressive increase in the incidental detection of tumors and the percentage of
      patients candidates to conservative surgery due to the decrease in size. It is
      easy to differentiate between adenocarcinoma and angiomyolipoma, up to 85% of the
      cases, but the rest of the tumors do not have specific characteristics. For small
      size masses, smaller than 3 cm, ultrasound sensitivity is clearly inferior to CT
      scan. Power color Doppler helps to confirm the existence of solid masses and
      helps a better differential diagnosis with pseudo tumors. CONCLUSIONS: The modern
      ultrasound techniques provide a high cost-effectiveness both in detection and
      definition of the nature of small size renal masses.

PMID- 16800132
TI  - [The usefulness of ultrasonography and Doppler ultrasound in renal
      transplantation].
AB  - OBJECTIVES: The aim of the study is to analyze the usefulness of ultrasound and
      Doppler ultrasound for the evaluation of transplant donors and recipients, for
      renal transplant follow-up and for the resolution of surgical complications after
      renal transplant. METHODS: Abdominal ultrasound was performed in donors and
      recipients of renal grafts. In the recipients with vascular risk factors a
      Doppler ultrasound of the iliac and lower limb arteries was systematically done.
      Doppler ultrasound was performed in the first and seventh day after renal
      transplant, as well as for graft dysfunction at any moment. RESULTS: Recipient
      ultrasound informs about the existence of acquired renal cystic disease and
      Doppler ultrasound allows evaluating the vascular state of high risk recipients.
      In the immediate post-transplant period ultrasound studies are useful for
      detection of vascular complications, graft obstruction and to control the
      evolution of acute rejection and acute tubular necrosis. Finally, ultrasound is
      the technique of choice in the endourological management of surgical
      complications after renal transplant. CONCLUSION: Ultrasound under urologic
      control is essential in the evaluation of the kidney transplant recipient, post
      transplant follow-up and in the resolution of surgical complications.

PMID- 16800133
TI  - [Diagnosis and follow-up of benign prostatic hyperplasia by ultrasound].
AB  - OBJECTIVES: The aim of the study is to analyze the utility of ultrasound in the
      evaluation and treatment selection of patients with benign prostatic hyperplasia
      (BPH). METHODS: A total of 5000 patients older than 50 years and with prostatic
      symptoms were evaluated with abdominal ultrasound and in selected cases with
      transrectal ultrasound. RESULTS: The first ultrasonographic sign of BPH is the
      increase of anteroposterior and longitudinal diameters. Prostatic volume is
      measured with a safety of 80%, post-void volume and indirect signs of bladder
      obstruction are also determined by ultrasound. Upper urinary tract pathological
      conditions can be also detected. CONCLUSIONS: Ultrasound associated with PSA and
      urinary flow are adequate to evaluate and select treatment in patients with BPH.

PMID- 16800134
TI  - [Prostate cancer and transrectal ultrasound].
AB  - We describe the ultrasonographic changes prostate cancer can produce, and analyze
      the usefulness of ultrasonography in the study of this disease. Transrectal
      ultrasound does not have enough sensitivity and specificity for the diagnosis,
      metastasic study, and diagnosis of recurrences after radical prostatectomy.
      Nevertheless the ultrasound study of the morphology of the prostatic apex may be
      useful for the planning and performance of the apex dissection during radical
      prostatectomy.

PMID- 16800135
TI  - [Tridimensional ultrasound of the prostate].
AB  - OBJECTIVES: To present the examination technique of grayscale tridimensional
      transrectal prostatic ultrasound and its clinical viability. To define the
      ultrasonographic patterns and to report the clinical experience of our group.
      METHODS: We analyze selected exams from a database of more than 600 digitally
      stored tridimensional transrectal prostatic ultrasounds performed with a robotic
      probe. We collect the opinion and observations of the examiners, all of them
      experts on prostatic ultrasound. Each case has been completed with pathologic and
      clinical data. RESULTS: The time spent for each test was less than three minutes,
      achieving good quality, reproducible exams. The analysis of the front view offers
      the greatest contribution in comparison to the conventional technique, allowing a
      more clear detection of structures such as the junction with the seminal
      vesicles, the capsular contour, and urethra. CONCLUSIONS: Tridimensional
      transrectal prostatic ultrasound is an imaging test applicable in the clinical
      practice which offers quality images and may provide great benefits for the
      diagnosis and local staging of prostate cancer, by means of the analysis of the
      front view.

PMID- 16800136
TI  - [Evolution of the transrectal ultrasound guided prostatic biopsy technique].
AB  - To analyze the various techniques of transrectal ultrasound guided biopsy of the
      prostate described in the literature, as well as the anesthesia modalities for
      its performance. The diagnostic yield of the classic sextant biopsy, described 16
      years ago and considered the standard technique ever since, has been overcome by
      the extended biopsy techniques (greater number of cores from more prostatic areas
      in each biopsy). Although their intra-study yield is better than sextant biopsy,
      the scarce randomized studies have not demonstrated a statistically significant
      improvement. These new techniques of extended biopsy significantly increase the
      rate of minor complications, not the major. It has not been demonstrated an
      increase in either the perception of pain or the diagnosis of non-significant
      tumors. Any anesthetic technique employed diminishes significantly the perception
      of pain by the patient. The periprostatic nerve blockage with infiltration of
      lidocaine is better than the rest of the techniques. The best technique of
      infiltration and the most effective lidocaine dose are to be defined yet. These
      techniques do not increase complications and only prolong the procedure briefly.

PMID- 16800137
TI  - [Transrectal ultrasound-guided prostatic biopsy: contribution of an ultrasound
      diagnostic unit after ten years of experience].
AB  - OBJECTIVES: Although transrectal ultrasound-guided (TRUS) prostatic biopsy is the
      procedure of choice for the diagnosis of prostate cancer (PC), neither the ideal
      number of cores nor the number of repeated biopsies, nor the required diagnostic
      yield have been established. After our experience of ten years with TRUS biopsy
      we perform a review of the technique and its indications. METHODS: PSA,
      ultrasound features, and pathologic data of 6000 patients undergoing modified
      sextant TRUS biopsy between 1994 to December 2002 were collected. 222 patients
      undergoing ten-core TRUS biopsy were included in an experimental group to study
      the role of the extended biopsy. The contribution of the extra cores to the
      diagnostic yield in the experimental group was studied to determine the
      effectiveness of the extended biopsy, using as a control group 552 patients
      undergoing sextant TRUS biopsy during 2002. Both groups were comparable for the
      study variables at the start of the study. RESULTS: The incidence of PC in the
      first biopsy in the group of 6000 patients was 39.1% (2345/6000). Patients with
      PSA between 4 and 10 ng/ml have an incidence of PC greater than 50% among
      prostates smaller than 20 cc, diminishing down to 8.9% in those greater than 50
      cc. The percentage of PC among patients with negative digital rectal examination
      (DRE), normal TRUS, and PSA below 4 ng/ml was 16.7%. The diagnostic yield for PSA
      density lower than 0.11 ng/ml/cc was lower than 8%. The free/total PSA ratio
      shows a 13.7% incidence of PC with values higher than 0.24. Multivariate logistic
      regression analysis showed that the only non-significant parameter was free/total
      PSA. Sixty (27.15%) patients of the extended TRUS biopsy group had PC. Only 2.25%
      of the 221 patients benefited from the augmented number of biopsies. There were
      no significant differences in the figures of prostate cancer between groups. Only
      PSA and volume where significant in the multivariate logistic regression
      analysis; number of samples, PSA density and age lacked of influence in the
      detection of PC. CONCLUSIONS: The sextant biopsy model obtaining cores from the
      lateral horns of the prostate continues to be the reference for TRUS biopsy, and
      the extended biopsy is not applicable to all patients from the beginning do to
      the small increase in the diagnostic yield. Isolated PSA may not be the unique
      reference to indicate TRUS biopsy, being volume, in our experience, a definitive
      factor for the adjustment of high risk levels.

PMID- 16800138
TI  - [Local anesthesia significantly improves the tolerance of prostate biopsy].
AB  - Transrectal biopsy is one of the most frequent procedures in urological practice.
      Generally, transrectal biopsies have been practiced without anesthesia, because
      of a supposed good tolerance. Nevertheless, it is not infrequent to find patients
      with a high level of pain and adverse effects attributable to such procedure.
      OBJECTIVES: In the present article the effect of transrectal local anesthesia in
      order to significantly diminish the perception of pain by the patient is
      evaluated. METHODS: A total of 131 consecutive patients undergoing transrectal
      prostate biopsy are included in the study. After randomization, 76 patients were
      biopsiated with anesthesia and 55 represent the control group. Cases and control
      groups do not differ in age or prostate volume. Anesthesia consisted on a
      periprostatic nerve blockage with injection of 5 cc of 1% mepivacaine solution in
      the angle between prostate and seminal vesicles bilaterally. A visual analogical
      scale for pain was used; it was given to the patient at the end of the procedure.
      RESULTS: Mean pain value was 2.41 with a median of 2.0 in the group with
      anesthesia, and 4.02 with a median of 4 in the control group. A Student's t test
      comparing the means showed a statistically significant difference of 1.61 (p <
      0.0001). Pain in the scale was 66% greater in the control group. CONCLUSION: The
      use of anesthesia in the performance of transrectal biopsies significantly
      diminishes the perception of pain by patients. This effect, along with the
      tendency to increase the number of biopsies, will result in short time in a more
      generalized use of local anesthesia.

PMID- 16800139
TI  - [The role of transrectal ultrasound on prostatic cryotherapy and brachytherapy].
AB  - OBJECTIVES: Transrectal ultrasound is the method that gives a direct image of the
      prostate, its limits, structural and morphologic anomalies, and anatomical
      relations. Therefore, prostate volume is easily determined, being the first step
      for the application of certain therapeutic procedures. Prostatic cryotherapy and
      brachytherapy have been developed over the last years as minimally invasive
      options for the treatment of prostate cancer. Transrectal ultrasound of the
      prostate has allowed the application of these technologies in the daily practice,
      guaranteeing high efficacy and safety indexes. Cryosurgery is the controlled
      freezing of tissues. Prostatic transrectal ultrasound is the only method able to
      show the real-time evolution of prostatic cryoablation, allowing the urologist to
      control the evolution of the ice ball and to reach the targeted anatomical
      structures guaranteeing the oncological objectives, and diminishing complications
      and sequels. Brachytherapy, as a local intraprostatic radiotherapy, needs exact
      volume and dose calculations before the implant of the radioactive source within
      the gland. With transrectal ultrasound of the prostate, ultrasound-tomographic
      cuts are made for prostatic volume calculation and planimetry Once dosimetry is
      completed, real-time transrectal ultrasound control is necessary to perform the
      implant of the needles loaded with the seeds. Today, prostate cryotherapy and
      brachytherapy would be inconceivable without transrectal ultrasound.

PMID- 16800140
TI  - [Ultrasound for the diagnosis of female urinary incontinence].
AB  - OBJECTIVES: The value of ultrasonography for the study of female urinary
      incontinence has been redefined over the last years. METHODS: We review the
      literature about the value of ultrasound in the workup of females with urinary
      incontinence, mainly transperineal ultrasound for the female stress urinary
      incontinence (SUI). RESULTS: Many papers have been published over the last few
      years. Upper urinary tract ultrasound has not a place in the workup of genuine
      female SUI. Transperineal ultrasound allows to evaluate the mobility of the
      bladder neck and urethra, the thickness of the bladder wall, the funnel shape of
      the bladder neck, the presence of SUI or pelvic organ prolapse (POP), to
      visualize mesh implants, to help with biofeedback, and to evaluate changes after
      surgical treatment. CONCLUSIONS: Ultrasounds in general, and transperineal or
      translabial ultrasound in particular, are in the process of becoming the standard
      diagnostic method in urogynecology. Their wide availability, the standardization
      of parameters, the possibility of evaluating not only the bladder but also the
      levator ani muscle or pelvic organ prolapses (POP) contribute to this fact. It
      allows to obtain data in a non invasive way before and after therapy.

PMID- 16800141
TI  - [Testicular ultrasonography].
AB  - OBJECTIVES: To review the contribution of ultrasound to the differential
      diagnosis of scrotal pathology, both testicular and adnexal. METHODS: We
      performed a bibliographic review on the topic, adding the experience of our Unit
      over the years; we classified the pathology in testicular and extratesticular,
      separating liquid and solid lesions, and a miscellaneous group of unclassifiable
      cases. RESULTS: Currently, ultrasonography with high frequency equipment allows
      not only to differentiate between intra and extratesticular lesions, but also to
      identify specific lesions, the manage of which may include follow-up without need
      of unavoidable surgery. CONCLUSIONS: Ultrasonography is a painless simple test
      that may be repeated without inconvenience so that it is the first test to be
      indicated for any problem of the scrotal content.

PMID- 16800142
TI  - [The significance of private health insurance in future medical care].

PMID- 16800143
TI  - [Chronic pain and depression].
AB  - Pain and depression are a severe burden on the patient and on the health system.
      The diseases have many common pathophysiological aspects and a high level of
      comorbidity. In this article the different diagnostic tools and options for the
      treatment of pain and depression are described. Prognostic factors for the course
      of the diseases are given. Documentation of the disease is important for
      treatment, for questions in the field of healthcare and in order to furnish a
      medical opinion. Important diagnostic assessments and differential diagnoses are
      described.

PMID- 16800144
TI  - [Medical assessment of psychosomatic illnesses in the field of short-term
      disability compensation insurance: advantages of a multidimensional structured
      guideline].
AB  - The aim of the medical report in the area of short-term disability claims caused
      by psychological and psychosomatic disorders is to make a valid prognosis on the
      further development of absenteeism and/or to estimate the return-to-work
      probability of the claimant. An analysis of the current practice of determining
      the validity of claims caused by psychosomatic illnesses shows that it is
      inadequate and unsatisfactory, mainly as a result of its reliance on a cross
      sectional based judgement. The authors present a structured guideline (Multi
      Axial-Psychodiagnostic for short-term disability claims, MAP-KTG), which
      supports, via a multi-dimensional diagnosis process, the validation of the
      psychological and psychosomatic symptoms of the claimant. It is also used to
      assess the amount of functional disability with a higher degree of accuracy. The
      determination of the prognosis, with regard to future work prospects, can be
      obtained by applying a list of empirically generated variables proven to be
      associated with the return-to-work probability.

PMID- 16800145
TI  - [Medical insurance consultation through the medical society in the PKV--a
      quantitative analysis].
AB  - Insurance medical consultation by a medical consultant or medical director is
      well established at many companies in the German private health insurance sector.
      Nevertheless, the field of activity of the medical consultant is hardly known to
      the public and even less scientifically investigated. The present study deals
      with a quantitative analysis of insurance medical enquiries to medical
      consultants. For this, the total of all insurance medical enquiries in a whole
      year have been checked and classified. The total of 5116 enquiries shows that a
      large demand for consultation refers to the medical necessity of medicaments,
      followed by consultation on complementary and alternative medicine (CAM). Further
      important fields of consultation are the assessment of out-patient and in-patient
      psychotherapy, the verification of the extent of physical measures, the duration
      of hospital treatments, the extent of laboratory testing, the examination of new
      medical methods and the definition of cure measures in comparison with hospital
      treatment. Increasing demand exists for the definition of the necessity of out
      patient and in-patient operations, the definition of cosmetic surgery and
      medically necessary plastic surgery and for questions of reproductive medicine.
      There is also increasing demand for consultation regarding lifestyle drugs and
      anti-aging medicine.

PMID- 16800146
TI  - [Above elbow amputation due to acupuncture treatment?].
AB  - Opinions of acupuncture experts should always be sought in any lawsuit or claim
      for compensation involving sequelae of acupuncture treatment. Overall,--in the
      hands of experienced acupuncturists--acupuncture is very safe but not without
      minor adverse events. However, serious adverse events are extremely rare,
      especially the risk of a serious vascular lesion. In contrast, inflammatory bowel
      disease is an independent and disease specific risk factor for thromboembolism,
      especially if the disease is highly active.

PMID- 16800147
TI  - [Environmental medicine clarification of neurodermatitis for 3000 euro].

PMID- 16800148
TI  - [The top ten sciences in 2005].

PMID- 16800149
TI  - [Important diabetes gene detected].

PMID- 16800150
TI  - [The failure of naturopathy].

PMID- 16800151
TI  - A hybrid PHB-hydroxyapatite composite for biomedical application: production, in
      vitro and in vivo investigation.
AB  - Samples of a hybrid composite of polyhydroxybutyrate (PHB), a biodegradable
      polyester, and hydroxyapatite (HA), with different PHB/HA ratios, have been
      prepared using mechanical-physical method. Electron microscopy, X-ray structure
      analysis and differential thermal analysis have been used to investigate the
      structure and physicochemical properties of the composite, depending on the
      PHB/HA ratio. The properties of the surface of the HA-loaded composite are
      significantly different from those of the pure polymer. As the HA percentage in
      the composite increases, free interface energy, the cohesive force, i.e., the
      strength of the adhesive bond between the composite surface and the water phase,
      and surface wettability increase. The HA percentage of the composite does not
      influence its melting temperature, but affects the temperature for the onset of
      decomposition: as the HA content increases from 0 to 10% (w/w), Td decreases from
      260 degrees C to 225 degrees C. The degree of crystallinity of PHB/HA increases
      from 77% to 89% with an increase in the HA fraction from 10% to 50%. Functional
      properties of the composites have been investigated in vitro and in vivo. The
      best parameters of growth and differentiation of murine marrow osteoblasts are
      registered on PHB/HA samples containing 10% and 20% HA. In ectopic bone formation
      assay it has been proven that the hybrid PHB/HA composites can function as
      scaffolds and that bone tissue develops on their surface and in pores.

PMID- 16800152
TI  - Dextran derivatives modulate collagen matrix organization in dermal equivalent.
AB  - Dextran derivatives can protect heparin binding growth factor implied in wound
      healing, such as transforming growth factor-beta1 (TGF-beta1) and fibroblast
      growth factor-2 (FGF-2). The first aim of this study was to investigate the
      effect of these compounds on human dermal fibroblasts in culture with or without
      TGF-beta1. Several dextran derivatives obtained by substitution of
      methylcarboxylate (MC), benzylamide (B) and sulphate (Su) groups were used to
      determine the effects of each compound on fibroblast growth in vitro. The data
      indicate that sulphate groups are essential to act on the fibroblast
      proliferation. The dextran derivative LS21 DMCBSu has been chosen to investigate
      its effect on dermal wound healing process. Fibroblasts cultured in collagenous
      matrices named dermal equivalent were treated with the bioactive polymer alone or
      associated to TGF-beta1 or FGF-2. Cross-sections of dermal equivalent observed by
      histology or immunohistochemistry, demonstrated that the bioactive polymer
      accelerates the collagen matrices organization and stimulates the human type-III
      collagen expression. This bioactive polymer induces apoptosis of myofibroblast,
      property which may be beneficial in treatment of hypertrophic scar. Culture media
      analyzed by zymography and Western blot showed that this polymer significantly
      increases the secretion of zymogen and active form of matrix metalloproteinase-2
      (MMP-2), involved in granulation tissue formation. These data suggest that this
      bioactive polymer has properties which may be beneficial in the treatment of
      wound healing.

PMID- 16800153
TI  - Effect of solvent mixture on the properties of temperature- and pH-sensitive
      polysaccharide-based hydrogels.
AB  - Novel partially biodegradable, temperature- and pH-sensitive polysaccharide-based
      hydrogels (NDF) were synthesized from modified dextran (dextran-maleic acid, Dex
      MA) and N-isopropylacrylamide precursors over a wide range of mixed solvent
      ratios of dimethyl formamide (DMF) to water. N-Isopropylacrylamide monomers were
      chosen to impart thermo-responsive capability to Dex-MA, while Dex-MA was chosen
      to impart pH-responsive capability to N-isopropylacrylamide. The pH-sensitive
      precursor (Dex-MA) was synthesized by reacting dextran with maleic anhydride in
      the presence of triethylamine catalyst. To fabricate multi-stimuli hybrid
      hydrogel networks, both Dex-MA and N-isopropylarylamide precursors were photo
      cross-linked via UV at a fixed Dex-MA to N-isopropylarylamide feed ratio over a
      wide range of DMF to water mixed solvent ratios. The newly synthesized
      PNIPAAm/Dex-MA hybrid hydrogels (NDF) were characterized by Fourier transform
      infrared spectroscopy for chemical structure determination, differential scanning
      calorimetry for thermal analysis and scanning electron microscopy for
      morphological study. The properties of the hybrid hydrogels, such as thermo
      induced deswelling, pH-sensitivity, ionic strength sensitivity and thermo
      reversibility, were also examined. The swelling data obtained clearly showed that
      newly synthesized multi-stimuli NDF hydrogels exhibited multi-responsive
      capability to external stimuli like temperature and pH. The morphological data
      obtained showed that this new class of PNIPAAm/Dex-MA hybrid hydrogels had a wide
      range of unique three-dimensional porous network structures that depended on the
      composition ratio of the mixed DMF/water solvent during cross-linking reaction.
      This unique but versatile 3D porous network structures of NDF hydrogels were
      correlated to the data from thermo-induced swelling behavior, thermo
      reversibility, pH-dependent swelling and ionic strength sensitivity.

PMID- 16800154
TI  - Electrospinning of hexanoyl chitosan/polylactide blends.
AB  - The electrospinning of hexanoyl chitosan (H-chitosan), polylactide (PLA) and
      their blends was performed using chloroform, dichloromethane or tetrahydrofuran
      as a spinning solvent. The as-spun PLA fibers appeared to be cross-sectionally
      round, with rough surface morphology, while the as-spun H-chitosan fibers were
      flat with smooth surface morphology. Electrospinning of the H-chitosan/PLA blend
      solutions in chloroform with the H-chitosan solution content of less than or
      equal to 50% (w/w) produced continuous fibers without the presence of beads,
      while that of the blend solutions in dichloromethane produced beaded fibers or
      even just beads at high H-chitosan solution contents. The size of the as-spun
      fibers from blend solutions with a H-chitosan solution content of less than or
      equal to 50% (w/w) was found to decrease with increasing the H-chitosan solution
      content. Thermal characteristics and crystalline structure of selected as-spun
      fibers from pure and blend solutions in chloroform were characterized by
      thermogravimetric analysis, differential scanning calorimetry and wide-angle X
      ray diffraction (WAXD) techniques.

PMID- 16800155
TI  - Direct grafting of RGD-motif-containing peptide on the surface of
      polycaprolactone films.
AB  - Direct surface modification of biodegradable polycaprolactone (PCL) was performed
      without the necessity of synthesis of functionisable co-polymers. An easy-to
      perform three-step procedure consisting of amination, reaction with hetero
      bifunctional cross-linkers and conjugation of an RGD-motif-containing peptide was
      used to modify polymer films and improve the attachment of endothelial cells. The
      biological activity of modified surfaces was assessed by estimating microvascular
      endothelial cell attachment. Covalent coating with RGD resulted in an
      approximately 11-fold increase of endothelial cell attachment on modified PCL
      surfaces compared with untreated polymer. The specificity of the attachment
      enhancement was confirmed by using a control peptide. It is concluded that
      chemical surface modification is an appropriate method of rendering degradable
      polymers, such as PCL, cell-adhesive.

PMID- 16800156
TI  - Stabilization of gold nanoparticles by hydrophobically-modified polycations.
AB  - Surface-modified gold nanoparticles have pronounced benefits in the biomedical
      field due to their significant interaction with delivery materials. In the
      present study we used hydrophobically-modified polycations (i.e., N-acylated
      chitosan) to stabilize gold nanoparticles. Aliphatic hydrophobic groups, having
      carbon chains of different lengths, were first grafted onto the backbone of
      chitosan by N-acylation with fatty-acid chlorides in order to increase its
      hydrophobicity. Gold nanoparticles stabilized with native chitosan and N-acylated
      chitosan were prepared by the graft-onto approach. Chemical modification and its
      quantification were studied by Fourier-transform infrared (FT-IR) spectroscopy.
      Further, the stabilized gold nanoparticles were characterized by different
      physico-chemical techniques such as UV-Vis, FT-IR, TEM, TGA and DLS. Spectral
      studies of gold nanoparticles show the backbone and the side chain functional
      groups of chitosan were not cleaved during the conjugation process. TEM
      observations revealed that the modified chitosan gold nanoparticles were well
      dispersed and spherical in shape with average size around 10-12 nm in triply
      distilled water at pH 7.4, whereas the native chitosan gold nanoparticles
      appeared as clusters with 9.9 nm as average diameter and were dispersed only in
      dilute HCl. The size of modified chitosan gold nanoparticles varied depending on
      the length of grafting molecules.

PMID- 16800157
TI  - A polymeric micelle system with a hydrolysable segment for drug delivery.
AB  - A potential anti-cancer drug-delivery polymeric micelle system with an in vitro
      degradation half-life of about 48 h that releases its drug upon application of
      ultrasound was synthesized. This vehicle was composed of an amphiphilic co
      polymer, poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl
      methacrylate-lactate(n)). The degree of polymerization of the lactate side group,
      n, was 0, 3 or 5. The molar ratio of NIPAAm to HEMA-lactate(n) to PEO in
      polymerization was optimized to produce an in vitro polymeric micelle half-life
      of about 48 h at 40 degrees C. 1,6-Diphenyl-1,3,5-hexatriene (DPH) was used as a
      fluorescent probe to study the hydrophobicity of the cores of the polymeric
      micelles. The results showed that the cores of the polymeric micelles were
      hydrophobic enough to sequester DPH and the anti-cancer drug doxorubicin (Dox).
      Dox was encapsulated into the polymeric micelles having a molar feed ratio of
      NIPAAm to HEMA-lactate3 to PEO equal to 20:5:1; this drug was released upon the
      application of low-frequency ultrasound. The Dox release was about 2% at room
      temperature and 4% at body temperature, and the drug returned to the polymeric
      micelles when insonation ceased.

PMID- 16800158
TI  - Simulating the real world of antihyperglycaemic therapies in type 2 diabetes.

PMID- 16800159
TI  - A model of long-term metabolic progression of type 2 diabetes mellitus for
      evaluating treatment strategies.
AB  - AIM: To develop a novel metabolic computer model of the natural lifetime
      progression of type 2 diabetes that generates dynamic risk factor trajectories
      consistent with prespecified lifetime therapeutic strategies, in order to enhance
      the long-term economic and outcome modelling of type 2 diabetes and its
      complications. METHODS: The main model drivers of progressive disease were
      changes in insulin sensitivity and islet beta-cell function derived from an
      analysis of follow-up results from the Belfast Diet Study. These were related to
      clinical measures through an adaptation of the homeostasis model assessment.
      Established causal relationships estimating body mass index, lipids and blood
      pressure from measures of glycaemia and plasma insulin were calibrated using
      Third National Health and Nutrition Examination Survey (USA) data, standardizing
      for age, sex, ethnicity and smoking. The effects of individual interventions were
      calibrated using published trial evidence, in line with the current understanding
      of the main modes of action of each agent. RESULTS: A comparison of the effects
      of common therapies using the model showed both similarities and differences.
      Large improvements in glycaemic control from lifestyle modifications, further
      enhanced by oral glucose-lowering drugs or insulin, were reproduced. Projections
      comparing lifetime therapeutic strategies suggest that simple guidelines may not
      always be valid. CONCLUSION: This novel mathematical model using evidence from
      the long-term natural history of type 2 diabetes is able to project the expected
      effects of various antihyperglycaemic therapies. Coupled with an economic model,
      this metabolic model may provide a mechanism for healthcare professionals and
      policymakers to evaluate different long-term strategies for the management of
      type 2 diabetes.

PMID- 16800160
TI  - Cost-effectiveness of rosiglitazone combination therapy for the treatment of type
      2 diabetes mellitus in the UK.
AB  - INTRODUCTION: Recent clinical trial results have demonstrated that, in patients
      with type 2 diabetes, second-line treatment of rosiglitazone in combination with
      metformin can lead to significant improvements in the control of fasting plasma
      glucose/ glycosylated haemoglobin A1c (HbA1c) after the failure of metformin
      monotherapy. Our objective was to assess the cost-effectiveness of the use of
      rosiglitazone in combination with metformin in overweight and obese patients with
      type 2 diabetes in the UK, failing to maintain glycaemic control with metformin
      monotherapy compared with conventional care using metformin in combination with
      sulfonylurea. METHODS: The Diabetes Decision Analysis of Cost--type 2 (DiDACT)
      model, an established long-term economic model of type 2 diabetes, which projects
      the relationship between treatment and HbA1c over extended periods, was used to
      determine the health outcomes and economic impact for matched age and sex cohorts
      of 1000 patients with type 2 diabetes. The perspective was that of the UK
      National Health Service and all costs were in UK pounds sterling. RESULTS:
      Treatment with rosiglitazone in combination with metformin provides better
      glycaemic control over the remaining lifetime of patients than metformin and
      sulfonylurea combination therapy. Patients treated with rosiglitazone combination
      therapy were predicted to have a longer life expectancy, gaining 123 and 140
      additional life years per 1000 patients in the obese and overweight cohorts,
      respectively. Improvements in morbidity and a delay in the start of insulin
      therapy resulted in a projected improvement in quality of life. These effects
      combine with projected improved survival to yield 131 and 209 additional quality
      adjusted life-years (QALYs) per 1000 patients in the obese and overweight
      cohorts, respectively. Discounted incremental cost-effectiveness ratios were
      estimated at pounds 16,700 per QALY gained for the obese cohort and pounds 11,600
      per QALY gained for the overweight cohort. CONCLUSION: The model predicts that
      rosiglitazone in combination with metformin is a cost-effective treatment in the
      UK for both obese and overweight patients failing on metformin monotherapy,
      compared with conventional therapy using metformin in combination with
      sulfonylurea.

PMID- 16800161
TI  - Cost-effectiveness of rosiglitazone oral combination for the treatment of type 2
      diabetes in Germany.
AB  - AIMS/HYPOTHESIS: To assess the cost-effectiveness of rosiglitazone in combination
      with other oral agents for the treatment of overweight and obese patients with
      type 2 diabetes in Germany. METHODS: The Diabetes Decision Analysis of Cost--type
      2 model was adapted for clinical practice and healthcare financing rules in
      Germany. The model was calibrated using Cost of Diabetes in Europe Type 2 study
      data and national statistics. The perspective is that of the sickness funds, and
      includes all hospital inpatient, ambulatory, rehabilitation, and diabetes
      therapy, other medications, and sickness leave. The model simulates lifetime
      treatment histories and associated health outcomes and costs for age and sex
      matched cohorts of 1000 overweight and obese patients. The measures of
      effectiveness used in the analysis were life-years and quality adjusted life
      years (QALYs). RESULTS: The combination therapy of rosiglitazone with metformin
      or sulfonylurea produces better glycaemic control than conventional care of
      metformin with sulfonylurea and insulin in most patients, extends the viability
      of oral therapy before requiring insulin, and typically leads to lifetime cost
      increases across all treatment types. The improvements in glycaemic control lead
      to survival gains and reductions in morbidity, because of the reduced risk of
      developing or progressing to later stages of complications. Improvements in
      morbidity and mortality generate additional QALYs. Costs and health outcomes
      combine to yield favourable incremental cost-effectiveness ratios, which fall
      below international 'willingness-to-pay' thresholds in the medium term.
      CONCLUSION: The model predicts that rosiglitazone in combination with other oral
      agents is a cost-effective intervention for the treatment of normal weight,
      overweight and obese patients with type 2 diabetes when compared with
      conventional care in Germany.

PMID- 16800162
TI  - Lifetime health consequences and cost-effectiveness of rosiglitazone in
      combination with metformin for the treatment of type 2 diabetes in Spain.
AB  - OBJECTIVE: To assess the lifetime diabetes health consequences and cost
      effectiveness in Spain of rosiglitazone in combination with metformin for the
      treatment of type 2 diabetes in overweight and obese patients failing to maintain
      glycaemic control with metformin monotherapy compared with conventional care of
      metformin in combination with either sulfonylureas or bedtime insulin. RESEARCH
      DESIGN AND METHODS: The Diabetes Decision Analysis of Cost--Type 2 was adapted
      for clinical practice and healthcare funding in Spain, and was calibrated with
      Spanish epidemiological, healthcare resource use and cost data, taking the
      perspective of the Spanish National Health System. The model simulates lifetime
      treatment histories, complications and consequences of type 2 diabetes, and
      associated health outcomes and costs for age and sex-matched cohorts of 1000
      overweight and obese patients. The primary health outcome measures compared are
      glycaemic control, time to insulin, incidence and prevalence of coronary heart
      disease, stroke, clinical nephropathy, ulceration and amputation, and severe
      visual loss, and incremental life-years and quality-adjusted life-years (QALYs).
      RESULTS: Rosiglitazone in combination with metformin produces better glycaemic
      control than conventional care of metformin in combination with either
      sulfonylureas or bedtime insulin in most patients, and extends the viability of
      combination therapy by between 6 and 13 years before requiring insulin.
      Rosiglitazone patients have a longer life expectancy, gaining between 106 and 175
      additional life-years per 1000 patients, experience fewer episodes of coronary
      disease and clinical nephropathy, and live for longer periods free of
      complications. The improvements in morbidity and mortality are projected to yield
      between 134 and 238 additional QALY per 1000 patients over their lifetime.
      Discounted incremental cost-effectiveness ratios range from euro 9406 to euro
      23,514 per QALY gained. CONCLUSION: The model predicts that rosiglitazone in
      combination with metformin is a cost-effective intervention for the treatment of
      both overweight and obese patients with type 2 diabetes when compared with
      conventional care in Spain.

PMID- 16800163
TI  - Factors associated with adherence to antiretroviral therapy.
AB  - The purpose of this study was to examine the relationship of sociodemographic
      characteristics, patient perceptions, and patient characteristics including
      spirituality, self-reported adherence, and highly active antiretroviral therapy.
      The convenience sample consisted of 120 English-speaking adults (60% male, 35%
      female, 5% transgendered) with HIV/AIDS from two HIV service agencies in a large
      metropolitan city in the southeastern United States. The mean self-reported
      adherence was 83.1% (SD = 15.7%). Adherence was significantly correlated with
      perceived support and absence of barriers, strong intentions to adhere, perceived
      effectiveness of the medications, higher levels of perceived general health,
      fewer years of HIV disease, and fewer years on antiretroviral medications.
      Existential well-being (e.g., viewing life as positive and having meaning) was a
      weak significant correlate. Backward regression analysis was conducted to
      identify a parsimonious model of predictors of adherence. The final model
      included presence of support and absence of barriers, fewer years of HIV
      infection, no current alcohol use, perceived severity of HIV, existential well
      being, and male gender. This model explained 19.4% of the variance in adherence
      (observed F[6, 100] = 5.6, p < .0001).

PMID- 16800164
TI  - Relationship of emotional intelligence and adherence to combination
      antiretroviral medications by individuals living with HIV disease.
AB  - Medications are an intentional and purposeful means to the successful management
      of many chronic diseases. In the treatment of disease caused by HIV, adherence to
      medication is of particular concern because any level of nonadherence, often a
      few missed doses, will lead eventually to the development of drug resistance.
      Many predictors of poor adherence to HIV medications have been identified as
      significant factors in adherence. Among these is the emotional aspect. The
      purpose of this study was to examine emotional intelligence (EI) and adherence to
      combination antiretroviral therapy in individuals who are infected with HIV. EI
      is defined as the ability to perceive and express emotions, facilitate emotions,
      understand and reason with emotion, and manage emotions. EI has been correlated
      with various aspects of success in life. In this study, EI was measured by the
      Mayer, Salovey, Caruso Emotional Intelligence Test. Adherence to medications was
      measured by self-report and defined as less than 10% missed doses of medications.
      Eighty-two participants were recruited from an urban hospital-based HIV clinic.
      Pearson's r was used to analyze the data for significance, and no correlation was
      reported. This data set was not large enough to prove significance,
      statistically, of the research question. However, an unexpected result of this
      study was that the overall EI scores for this particular population were markedly
      lower than the test norms. Further study would be warranted and recommended to
      explore El measurement in people at risk for HIV disease or in those who have the
      disease to further understand the impact of emotions and EI in this specific
      population.

PMID- 16800165
TI  - Health-related quality of life of HIV-infected children on complex antiretroviral
      therapy at home.
AB  - The study describes quality of life as perceived by parents and measured by the
      Child Health Questionnaire (CHQ-28) for a convenience sample of 33 HIV-infected
      children age 5 to 18 years cared for at home on complex antiretroviral drug
      regimens. When compared with normative data on healthy U.S. children, parent
      reports for the HIV-infected children did not differ significantly on the
      following CHQ concepts: role/social related to emotional, behavioral or physical
      problems; bodily pain; behavior; mental health; self-esteem; impact on parental
      time; family activities; and family cohesion. Parents perceived their children to
      be functioning at a level significantly lower than the norm in general health (t 
      6.47, p = .000), physical functioning (t -2.37, p = .024), and physical summary
      (t -3.80, p = .001). Parental impact-emotional was impressively higher than the
      norm (t -3.74, p = .001). Differences were independent of gender, primary
      language, ethnicity, and Centers for Disease Control and Prevention clinical
      classifications for pediatric HIV disease.

PMID- 16800166
TI  - Reconsidering the assessment of symptom status in HIV/AIDS care.
AB  - Symptom management is one of the predominant components of HIV/AIDS care.
      Frameworks that adequately posses sufficient construct validity and that reflect
      the symptom experience related to HIV disease, treatment, and medications have
      been limited. Without validated measures, nurses and other care providers are
      limited in their ability to accurately assess symptomology and to make
      appropriate changes to care regimens. The purpose of this article is to
      demonstrate a method for evaluating symptom status based on the Sign and Symptom
      Check-List for Persons with HIV disease (SSC-HIV) as well as to provide further
      support as to the validity of the SSC-HIV. The method to evaluate symptom status
      that is shown uses a measurement model approach that allows for the assessment of
      symptom clusters and may be more appropriate than traditional approaches. The
      sample for this analysis comes from the AIDS Time-Oriented Health Outcome Study.
      Results further support the SSC-HIV as a valid measure of HIV-related symptoms.

PMID- 16800167
TI  - Symptom management of HIV-related diarrhea by using normal foods: A randomized
      controlled clinical trial.
AB  - The purpose of this randomized clinical trial was to determine the efficacy of a
      dietary intervention to reduce the frequency of bowel movements and improve stool
      consistency as compared with subjects assigned to a control group. The study
      enrolled HIV patients with a history of three or more episodes of diarrhea for 3
      weeks or more. Seventy-five subjects were enrolled, of which 38 were randomized
      to the treatment group and 37 to the control group. Six study sessions were
      scheduled over a 24-week period. At 24 weeks, the stool frequency reduced 28% in
      the treatment group and 15% in the control group (F = 9.22, p < .001) and stool
      consistency improved 20% in the treatment group and 8% in the control group (F =
      9.98, p < .001). The results showed that the intervention was effective in
      reducing stool frequency and improving stool consistency in HIV patients with
      chronic diarrhea for up to 6 months of treatment.

PMID- 16800168
TI  - Social roles and health in women living with HIV/AIDS: A pilot study.
AB  - The purpose of this report is to share results from a pilot study about the
      social role experiences and health of women living with HIV/AIDS. This pilot was
      designed as part of a larger study undertaken to ensure cultural competence of
      measures and methods proposed for testing a model of role quality and health in
      culturally diverse low-income women. Thirteen women participated in the study
      (69% African American; 77% less than dollar 10,000 annual income; range of years
      since HIV diagnosis, 3-21). Measures of physical health, role quality, and
      psychological well-being previously used to test relationships among the
      variables in women with chronic illness were administered using a face-to-face
      interview format. Results indicated that the women experienced a number of HIV
      symptoms and coexisting health problems, moderate physical limitations, positive
      perceptions of their roles, moderate levels of well-being, and high depression
      scores. The pilot study represents the first step in the development of a theory
      based approach to understanding linkages among health and role quality in women
      with HIV.

PMID- 16800169
TI  - [Psoriasis and cancer: more than a chance link].

PMID- 16800170
TI  - [Treatment of keloids with shaving and cryosurgery: preliminary reports].
AB  - INTRODUCTION: Numerous treatments have been proposed in patients with keloid
      scars. Unfortunately, most exhibit poor efficacy. The preliminary results
      obtained in ten patients with large keloid scars treated by shaving followed by
      cryosurgery are reported. PATIENTS AND METHODS: Ten patients with one or more
      keloid scars were treated by shaving of the keloid immediately followed by
      cryosurgery of underlying scar tissue using an impedance of 500 k Ohms. Minimum
      post-treatment follow-up was 12 months. "Major response" was defined as a
      reduction in keloid thickness of 80% to 100%, "moderate response" as an
      improvement of 50% to 80% or partial relapse, and failure as an improvement of
      less than 50% or complete relapse after treatment. RESULTS: A total of 16 keloids
      in ten patients (7 men, 3 women) aged from 10 to 45 years old (mean age: 25
      years) were treated. Keloids were localised on the lower lobe of the ear (n=10),
      on the ear lobe (n=3), on the neck (n=1), on the pubis (n=1), and on the
      presternal area (n=1). Mean duration of keloids was 3.1 years (18 months - 10
      years). Mean follow-up was 23 months (12-56 months). "Major responses" were
      observed in 13 cases (82%) (3 cases required further treatment); "moderate
      response" was observed in 3 cases (18%). CONCLUSION: These preliminary results
      are highly encouraging since all patients showed improvement. Shaving associated
      with cryosurgery appears to us to be a useful treatment for large keloids scars,
      particularly after otoplastic surgery.

PMID- 16800171
TI  - [Skin diseases in the elderly: a multicentre Tunisian study].
AB  - INTRODUCTION: With progressive aging of populations, geriatric health care has
      become a major international issue for health authorities. However, little data
      is available about geriatric skin diseases. The aim of this study is to determine
      the pattern of skin disorders among elderly patients seen in private and public
      skin outpatient clinics in Tunis. PATIENTS AND METHODS: We performed a
      prospective, multicentre and descriptive study of all new skin diseases diagnosed
      in dermatological outpatients aged over 65 years. This study lasted one year
      (June 1999 to July 2000) and evaluated the activity of eleven Tunisian
      dermatologists in private or public practice, who collated all cases of skin
      diseases diagnosed in their practices. RESULTS: A total of 1518 patients with
      1550 new diagnoses were examined. Mean age was 72.6 years with a sex M/F -ratio
      of 1.41. Fungal infections were the most common conditions (16.9%), followed by
      tumors 12.8% (benign 63.3%), eczema (11.9%), keratinization anomalies (8.7%),
      bacterial infections (8.7%), viral infections (6.8%) and pruritus (6.4%). Fungal
      infections were mainly represented by toe-web intertrigo and onychomycosis. Basal
      cell carcinoma and epidermoid cysts were the most common malignant and benign
      tumors respectively. DISCUSSION: This study reflects the frequency of mycoses,
      benign tumors and eczema in elderly patients. This is consistent with the results
      of other studies of the literature showing eczema as the predominant skin
      disease. The high prevalence of mycosis in our study may be explained by climatic
      conditions (heat, moisture). Pruritus seems to be frequent in geriatric patients.
      Skin disorders are an important source of morbidity in elderly patients.

PMID- 16800172
TI  - [Dermatitis artefacta: retrospective study in 31 patients].
AB  - BACKGROUND: The outcome for patients with dermatitis artefacta is not well known.
      The primary objective of this single-centre retrospective study was to describe
      the initial clinical aspects and the prognosis of the disease. The secondary
      objective was to describe the somatic and psychological management and long-term
      treatment of these patients. PATIENTS AND METHODS: Records of patients with
      dermatitis artefacta followed in the dermatology department over the 15 last
      years were reviewed independently by 2 dermatologists. Diagnostic criteria
      consisted of evocative clinical pictures and the exclusion of other forms of
      dermatosis. Data collection included: file analysis, photographs, review
      questionnaires sent to general practitioner or completed during a phone call to
      patients (follow-up data). RESULTS: Thirty-one patient files were selected: 23
      women and 8 men, mean age 31 years (SD = 14.8). Clinical aspects included:
      erythema (50%), ulceration (37%), crust (23%) and blisters (17%). The main sites
      were the face (67%) and arms (43%). Topical treatment was prescribed in all cases
      and systemic treatment was prescribed in 23% of cases. Psychological support was
      offered to 65% of the patients and was accepted by 50%. A follow-up study was
      performed for 17 patients and showed serious complications in 4 cases consisting
      of psychosis (n=2) and/or severe self-mutilation (n=3) occurring over several
      years following diagnosis (5 years for one patient and 12 years for 2 patients).
      DISCUSSION: The results confirm the usual and characteristics of dermatitis
      artefacta such as predominance in young female patients, with lesions affecting
      visible areas (face, upper legs). In contrastwith published studies, no cases of
      attempted suicide were observed in our series, although severe dermatitis
      artefacta was evidenced in only a minority of patients.

PMID- 16800173
TI  - [Skin signs associated with epidermal growth factor inhibitors].
AB  - BACKGROUND: Inhibitors of epidermal growth factor receptors (EGFR) constitute a
      new alternative treatment for patients presenting certain advanced stage solid
      cancers (bowel, breast, ovary). Adverse cutaneous effects of these drugs are now
      starting to be described. OBSERVATIONS: Our study involved 2 men and 2 women with
      no previous history of acne included in a treatment protocol comprising EGFR
      inhibitors. Mean age was 52 years. The primary cancers were breast, ovary, bowel
      and unidentified. The EGFR inhibitors used were gefitinib (ZD1839) (2 cases),
      carnetinib (Cl1033) and cetuximab (IMC-C225). Skin lesions appeared after 7 days
      and included erythematous papules and follicular pustules of the face, back and
      upper chest. No comedons were seen, and there were no nodules or cysts. The
      severity of the rash resulted in discontinuation of treatment in 2 patients with
      complete disappearance of skin lesions in both cases. In one patient, reduction
      of the dosage of gefitinib (IMC-C225) led to gradual resolution of the rash.
      Histological examination of papules and pustules concluded on an acute
      suppurative folliculitis. Smears and cultures ofa nasal lesion and pustules
      revealed coagulase-positive Staphylococcus aureus in 2 patients. Combined
      doxycycline 100 mg daily and benzoyl peroxide was prescribed for 3 months and a
      favourable outcome was achieved after a mean 2 weeks. DISCUSSION: EGFR inhibitors
      act by inhibiting mechanisms oftumour proliferation in certain cancers at
      advanced stages or refractory to other treatments. Our findings in these four
      patients are similar to the published cases in terms of rapid onset of
      monomorphous, papulopustular, follicular eruption without comedons. Rapid
      response to cyclines and benzoyl peroxide is also reported in literature. This
      treatment must be instituted rapidly and patients must be informed about the
      cutaneous side-effects of EGFR inhibitors before the start of therapy. The
      pathophysiology of these eruptions is still unknown. Skin signs are probably due
      to interaction with EGFR functions, including overexpression of EGFR in
      keratinocytes and hair follicles.

PMID- 16800174
TI  - [Hepatocellular carcinoma revealed by prurigo].
AB  - BACKGROUND: Paraneoplastic cutaneous manifestations associated with
      hepatocellular carcinoma may allow early diagnosis and curative treatment.
      Chronic prurigo alone may reveal hepatocellular carcinoma hepatocellular
      carcinoma in the absence of any other abnormal laboratory results potentially
      indicative of hepatic disease. CASE REPORT: A 79-year-old woman was referred to
      our unit for prurigo beginning 3 months earlier, occurring night and day and
      causing insomnia. The initial results were completely normal. In the absence of
      improvement under treatment with dermal corticosteroids, additional
      investigations were performed, in particular, abdominal ultrasound. The latter
      showed a liver nodule of 1.5 cm in diameter. CT scan confirmed the presence of
      this nodule and revealed morphological changes consistent with hepatocellular
      carcinoma in segment VIII. Alpha-fetoprotein was elevated. Following surgical
      treatment of this hepatocellular carcinoma, skin lesions regressed without any
      further treatment. One year later, no relapse of skin lesions was observed and
      the patient was in complete remission regarding hepatocellular carcinoma.
      DISCUSSION: Prurigo may constitute a paraneoplastic sign of hepatocarcinoma, the
      prognosis of which depends upon the stage at which it is discovered. For small
      tumors (< 3 cm), surgery may be curative. Of the few cases reported in the
      literature, our patient is the first to undergo curative surgery thanks to early
      diagnosis.

PMID- 16800175
TI  - [Necrobiotic xanthogranuloma without monoclonal gammopathy and with a rapidly
      fatal outcome].
AB  - BACKGROUND: Necrobiotic xanthogranuloma is an extremely rare form of
      histiocytosis that presents clinically as yellowish infiltrated plaques or
      nodules. Ocular involvement is seen in over 80% of cases. Histopathology reveals
      numerous xanthomous histiocytes and collagen necrobiosis. Benign monoclonal
      gammopathy associated with myeloma is found in 80% of patients, but the course is
      normally long, with 100% survival at 10 years. CASE REPORT: A 76-year-old man
      presented skin lesions that subsequently became ulcerated. The clinical
      appearance and histopathological examination resulted in diagnosis of necrobiotic
      xanthogranuloma. No monoclonal gammopathy or myeloma was seen. The disease was
      marked by sensitivity to corticosteroids with failure of other therapies
      (cyclophosphamide, alpha interferon), onset ofcorticosteroid dependency,
      iatrogenic Cushing's syndrome and diabetes, which were in part responsible for
      the infectious complications and subsequent death of the patient. DISCUSSION:
      Necrobiotic xanthogranuloma is difficult to treat, even in the absence of myeloma
      or monoclonal gammopathy. Corticosteroids are probably the most efficacious
      treatment, but can give rise to multiple complications, resulting in this
      particular case in death of the patient.

PMID- 16800176
TI  - [Bullous pemphigoid sparing acquired lymphedema].
AB  - BACKGROUND: Bullous pemphigoid is an autoimmune disease, common in the elderly
      and generally of symmetrical and systemic localization. We report a case with
      sparing of the lower limb and acquired lymphedema secondary to lymph node
      surgery. CASE REPORT: A 74-year-old woman was hospitalized for a bullous
      eruption. The left lower limb was completely spared and was unaffected by
      pruritus. Acquired lymphedema was seen in this limb secondary to lymph node
      surgery. Standard histopathology tests confirmed the diagnosis of bullous
      pemphigoid with subepidermal blistering, while a direct immunofluorescence
      antibody test showed linear binding of IgG and C3 throughout the basement
      membrane. Western blotting revealed anti-BPAg2 antibodies. Skin biopsy on the
      lymphedema spared by the disease revealed no inflammatory infiltrate in the
      dermis. However, linear binding of anti-IgG and anti-C3 autoantibodies was
      observed. DISCUSSION: Other cases of localized bullous pemphigoid appearing on
      body areas treated by UV or radiotherapy have been reported. Cases of bullous
      pemphigoid with predilection for areas of lymphedema have also been previously
      described: the hypothesis has been advanced of reduced lymphatic flow, with
      increased antigen-antibody contact enabling better binding. Our case is original
      and, given the protective nature of this lymphedema, suggests two hypotheses.
      There could be deterioration of local cellular immunity, with decreased
      activation of T lymphocytes. They could also be impairment of nervous conduction,
      as suggested by the absence of pruritus, with partial or total inhibition of
      neurogenic inflammation.

PMID- 16800177
TI  - [Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma with aggressive course].
AB  - BACKGROUND: Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma is a recently
      described rare primary cutaneous lymphoma exhibiting aggressive clinical
      behavior. Only about twenty cases have been described in the literature. Below we
      report a case involving unusual association of cutaneous vasculitis and
      lymphoproliferation. CASE REPORT: A 42-year-old senegalese man was hospitalized
      for cutaneous nodular lesions, which rapidly spread and became necrotic and
      ulcerated. he had recent weight loss with fever and multiple enlarged lymph
      nodes. Cutaneous histological analysis showed epidermotropic dermal infiltrate
      comprising medium and large cd8+ cytotoxic t-cells of unusual angiocentricity
      with cutaneous vasculitis and fibrinoid necrosis. the patient died 4 months after
      initiation of treatment with multi-agent chemotherapy. DISCUSSION: This patient
      presented the characteristics of primary cutaneous CD8+ epidermotropic cytotoxic
      T-cell lymphoma described by Berti. The clinical findings in most cases consist
      of nodular and ulcerative cutaneous lesions. Histologically, the cutaneous
      infiltrate is composed of pleomorphic lymphocytes with marked and constant
      epidermotropism. Immunohistochemistry shows lymphocytes expressing a CD8+
      phenotype and cytotoxic proteins, which probably accounts for the local and
      systemic aggressiveness of the disease, as well as the angiodestructive nature of
      the infiltrate and the necrotic lesions.

PMID- 16800178
TI  - [Precocious mediastinal lipomatosis: a rare complication of systemic
      corticosteroid therapy].
AB  - BACKGROUND: Corticosteroid-induced lipomatosis results from hypertrophy within
      adipose tissue; the condition is frequently asymptomatic and its incidence is
      underestimated. We report a case of mediastinal lipomatosis that is rare in terms
      of both site and presenting symptoms. CASE REPORT: A 46-year-old woman with no
      disease history other than obesity with a weight of 90 kg had been treated since
      2002 for mixed connective tissue disease (profound lupus and dermatomyositis).
      She had been treated with oral corti costeroids (1 mg/kg/d). Two months after the
      start of treatment, she presented chest pains, resting dyspnea particularly
      aggravated in dorsal decubitus, chest edema in the subclavicular space and
      jugular turgescence. Chest x-ray revealed widening of all levels of the
      mediastinum. The chest CT scan showed lipomatosis throughout the entire
      mediastinum with no associated chest abnormalities or pericardial effusion. Rapid
      downward dosage adjustment ofcorticosteroids to 10 mg/d coupled with synthetic
      antimalarials resulted in gradual reduction of symptoms. The chest scan performed
      two months later short stabilization of the patient's mediastinal lipomatosis.
      DISCUSSION: The effects of long-term of glucocorticosteroid therapy are well
      known, in particular Cushing's syndrome. Lipomatosis has been described more
      recently and affects different axial regions. Mediastinal localization is seen in
      15% of patients treated. This presentation is less common than orbital and
      epidural localizations. Although often asymptomatic, as in our own report, it may
      present with worrying symptoms that pose real diagnostic problems. The diagnostic
      examinations of choice are CT scan or MRI. Regression following discontinuation
      or reduction of corticosteroids is inconsistent and often gradual.

PMID- 16800179
TI  - [Cutaneous calciphylaxis treated by autologous keratinocytes graft and subtotal
      parathyroidectomy].
AB  - BACKGROUND: Cutaneous calciphylaxis, seen most often in dialysis patients, is
      characterised by skin necrosis, and is a disabling and lifethreatening disease.
      Despite intensive topical treatment, recourse to parathyroidectomy is often
      necessary. We report the case of a female patient with skin necrosis due to
      calciphylaxis: pain and necrotic lesions were controlled by grafting of cultured
      autologous keratinocytes (Epibase). CASE REPORT: A 75-year-old woman with a 5
      year history of dialysis-dependent chronic renal failure secondary to
      nephroangiosclerosis presented a very painful necrotic ulceration on her left
      leg. In spite of an autologous patch grafts, the lesions rapidly deteriorated.
      Laboratory data showed high levels of calcium, phosphate and parathyroid hormone
      and imaging suggested parathyroidal adenoma. Although cutaneous biopsy was not
      performed, the diagnosis of cutaneous necrosis due to calciphylaxis with tertiary
      hyperparathyroidism was established. Treatment consisted of a low-calcium and low
      phosphorus diet with autologous keratinocytes grafts (Epibase). After the third
      application of keratinocytes, the pain disappeared, necrosis ceased and wound
      healing began. Subtotal parathyroidectomy was performed two months after the
      start of grafts. At three months, the patient was cured. DISCUSSION: .
      Calciphylaxis is an obstructive vascular disease secondary to calcification of
      the arterioles leading to ischemic tissue necrosis. Prompt diagnosis is essential
      since this disease is disabling and life-threatening due to sepsis and ischemic
      complications. In our case, autologous keratinocyte grafts allowed pain relief to
      be achieved within large expanses of cutaneous necrosis after correction of
      calcium and phosphorus levels, thereby allowing parathyroidectomy to be performed
      under optimal conditions.

PMID- 16800180
TI  - [Steal syndrome].
AB  - BACKGROUND: Ischemic steal syndrome is a complication of arteriovenous access
      creation for hemodialysis, and is little known among dermatologists despite the
      fact is fairly common and has a cutaneous presentation. Herein we report the case
      of a man presenting with serious ischemic injuries to the fingers associated with
      steal syndrome. OBSERVATION: A 49-year-old diabetic man presented with painful
      acrosyndrome of the left hand, with a necrotic ulcer on the third finger
      appearing 5 months after the creation of an arteriovenous access. Clinical
      examination showed marked pain relief after manual compression of the fistula.
      Arteriography showed an overfunctional fistula, causing decreased distal
      perfusion pressure, and this was consistent with the diagnosis of steal syndrome.
      Banding of the anastomosis was performed but was insufficient to spare the finger
      from amputation. DISCUSSION: The aim of our case-report is to increase awareness
      among dermatologists of this fairly frequent complication of arteriovenous
      accesses. We discuss the physiopathology, risk factors, clinical features and
      therapeutic management of this condition. Since diagnosis of steal syndrome is
      fairly straightforward, early detection is essential. Only adequate surgical
      management can avoid gangrenous manifestations leading to more or less widespread
      amputation.

PMID- 16800181
TI  - [Cutaneous expression and function of Toll-like receptors].

PMID- 16800182
TI  - [Cutaneous pathology in the elderly].

PMID- 16800183
TI  - [Immunohistochemical analysis of EGFR and HER-2 in patients with metastasizing
      melanoma, Merkel carcinoma and squamous cell carcinoma of the skin].

PMID- 16800184
TI  - [Autoimmune diseases and statins].

PMID- 16800185
TI  - [Highly thrombogenic forms of Behcet's disease associated with Castleman's
      disease and renal amyloidosis].

PMID- 16800186
TI  - [Periungual trichilemmal cyst of the big toe].

PMID- 16800187
TI  - [Facial rash in a pregnant woman].

PMID- 16800188
TI  - [Treatment of systemic scleroderma: update].

PMID- 16800189
TI  - [New contraceptives].

PMID- 16800190
TI  - [Chronic vulvar herpes].

PMID- 16800191
TI  - [Psoriasis].

PMID- 16800192
TI  - [Identification of a candidate gene in disseminated superficial actinic
      porokeratosis].

PMID- 16800193
TI  - [Syringocystadenoma papilliferum at an unusual site].

PMID- 16800194
TI  - [Kaposi's sarcoma in an AIDS patient after application of tacrolimus (Protopic)].

PMID- 16800195
TI  - Work demands, job insecurity and sickness absence from work. how productive is
      the new, flexible labour force?
AB  - BACKGROUND: We investigate one aspect of productivity--sickness absence--and ask
      whether job insecurity and high work demands are associated with increased
      sickness absence and, if so, whether mental or physical health mediates this
      association. We further investigate if having control at work modifies these
      associations. METHODS: We used cross-sectional survey data from 2,248 employees
      aged 40-44 years living in two cities of south-eastern Australia. Logistic
      regressions were used to compare the associations between job insecurity and
      demands among those with short (1-3 days) or long-term (> 3 days) sickness
      absence with those who had no sickness absence in the last four weeks. The
      mediating effects of mental and physical health were assessed by evaluating
      changes in the magnitude of the association between these work conditions and
      sickness absence. RESULTS: High job insecurity (OR = 3.28; 95% CI 1.54-6.95) and
      high work demands (OR = 1.62; 95% CI 1.13-2.30) were significantly associated
      with long-term, but not with short-term, sickness absence. These associations
      were unaffected by job control. Depression and anxiety explained 61% of the
      association between high work demands and long-term sickness absence and 30% of
      the association between job insecurity and long-term sickness absence.
      CONCLUSION: Difficult working conditions may reduce productivity by contributing
      to longer absences from work. IMPLICATIONS: Reforms intended to improve economic
      performance should address any potential health costs of insecurity or
      intensification, which could inadvertently decrease productivity, possibly
      through their impact on mental health.

PMID- 16800196
TI  - Cancer due to occupation in Australia.
AB  - OBJECTIVE: This paper reviews previous attempts to estimate the proportion of
      cancers caused by occupational factors in Australia and overseas and calculates
      an estimate of the burden of occupational cancer in Australia. METHODS: A
      literature review and discussion of previous estimations of occupationally caused
      cancers is used to inform the choice of data for a calculation of Australian
      estimates. Finnish estimates of the proportion of cancers caused by occupation
      were applied to Australian numbers of cancers. European Union estimates of the
      proportion of workers exposed to carcinogens were applied to Australian
      industrial profiles. RESULTS: There are many uncertainties in the available data
      necessitating several assumptions, and the results should be interpreted
      cautiously. In Australia, we estimate that 5,000 invasive cancers and 34,000 non
      melanoma skin cancers per year are caused by occupational exposures and 1.5
      million workers are exposed to known carcinogens. CONCLUSIONS AND IMPLICATIONS:
      These estimates are considerably higher than previous Australian estimates, and
      should act as a spur to elevate the importance of occupation as a cause of cancer
      in order to decrease the population burden of cancer.

PMID- 16800197
TI  - Multiple outbreaks of dengue serotype 2 in north Queensland, 2003/04.
AB  - OBJECTIVES: To describe the various investigations and responses to multiple
      outbreaks of dengue serotype 2 that occurred in north Queensland in 2003/04.
      METHODS: Details about each case were collated so as to target mosquito-control
      responses including control of mosquito breeding sites, interior spraying of
      selected premises, and a novel 'lure and kill' approach using lethal ovitraps.
      Phylogenetic analyses were undertaken to determine the genetic relatedness of
      viruses isolated during the outbreaks. RESULTS: Except for a two-month hiatus in
      mid-2003, the outbreaks continued for 16 months and included approximately 900
      confirmed cases, with three severe cases and one death. The available evidence
      suggests that the mosquito-control measures were effective, but delays in
      recognising the outbreaks in Cairns and the Torres Strait coupled with intense
      mosquito breeding contributed to the extensive nature of the outbreaks.
      Phylogenetic analyses showed that there had been only two major outbreaks, one
      that spread from Cairns to Townsville, the other from the Torres Strait to
      Cairns; both were initiated by viraemic travellers from Papua New Guinea.
      CONCLUSIONS: Phylogenetic analyses were essential in understanding how the
      outbreaks were related to each other, and in demonstrating that dengue had not
      become endemic. Further innovative approaches to dengue surveillance and mosquito
      control in north Queensland are necessary. IMPLICATIONS: Dengue outbreaks have
      become more frequent and more severe in north Queensland in recent years, raising
      the possibility that dengue viruses could become endemic in the region leading to
      outbreaks of dengue haemorrhagic fever.

PMID- 16800198
TI  - Willingness to offer chlamydia testing in general practice in New South Wales.
AB  - OBJECTIVES: To assess willingness of general practitioners (GPs) to offer
      chlamydia testing to patients, and to identify demographic and practice
      correlates associated with willingness to offer chlamydia testing. METHODS: A
      postal survey of practising GPs in New South Wales was undertaken in 2002 to
      assess management of STIs in general practice. A 15% (n = 1,020) stratified
      random sample, based on sex and area of practice, was selected. The overall
      response rate was 45.4% (n = 409). RESULTS: More than four out of five study
      participants reported that chlamydia testing should usually be offered to
      patients who had recently changed sexual partners or inconsistently used barrier
      methods such as condoms. While 76% of GPs would like to offer testing to young
      women, 65% were in favour of testing young men. Just over half (56%) felt that
      chlamydia testing should usually be offered to patients at the time of a Pap
      smear. Multivariate analyses revealed that female GPs were more likely to offer
      testing to young patients and to female patients at the time of a Pap smear. GPs
      who had postgraduate training in STls had double the odds of offering testing to
      young men and to female patients at the time of a Pap smear. CONCLUSIONS AND
      IMPLICATIONS: This paper reveals variations in GPs' willingness to offer
      chlamydia testing to patients. Special education programs highlighting the
      adverse health effects of chlamydial infection have the potential to improve GP
      involvement in chlamydia screening.

PMID- 16800199
TI  - Non-fatal disease burden associated with excess body mass index and waist
      circumference in New Zealand adults.
AB  - OBJECTIVE: To describe the relationship between two measures of body fat and
      selected non-fatal health conditions in the New Zealand adult population in 2003.
      METHOD: Data were obtained from the 2002/03 New Zealand Health Survey. A total of
      10,026 adults aged 25 years and over were classified according to measured body
      mass index (BMI) and waist circumference (WC). BMI classes were 18.5-24.9, 25.0
      29.9, 30.0-34.9, > or = 35.0 kg/m2. WC classes were < 94, 94-102, > 102
      centimetres (cm) for males and < 80, 80-88, > 88 cm for females. Prevalence rate
      ratio estimates for selected self-reported health conditions were calculated for
      males and females separately, adjusting for age, ethnicity, deprivation and
      smoking using logistic regression. RESULTS: Increasing BMI or WC class was
      associated with increasing prevalence of cardiovascular disease, diabetes, high
      blood pressure, high blood cholesterol, osteoarthritis, asthma and sleep
      disorders in both males and females. The association with depression was not
      statistically significant in either gender. Associations were strongest for
      diabetes and blood pressure, with adults in the highest BMI or WC class at least
      3.5 times more likely to have diabetes and 2-3 times more likely to have high
      blood pressure compared with those in the lowest classes. CONCLUSIONS: Increasing
      body fatness, defined by either BMI or WC, was associated with increased
      prevalence of many important health conditions. If the obesity epidemic is not
      halted or reversed, the impact on both the New Zealand population and health
      system will be considerable.

PMID- 16800200
TI  - How valid are self-reported height and weight? A comparison between CATI self
      report and clinic measurements using a large cohort study.
AB  - OBJECTIVE: To examine the relationship between self-reported and clinical
      measurements for height and weight in adults aged 18 years and over and to
      determine the bias associated with using household telephone surveys. METHOD: A
      representative population sample of adults aged 18 years and over living in the
      north-west region of Adelaide (n = 1,537) were recruited to the biomedical cohort
      study in 2002/03. A computer-assisted telephone interviewing (CATI) system was
      used to collect self-reported height and weight. Clinical measures were obtained
      when the cohort study participants attended a clinic for biomedical tests.
      RESULT: Adults over-estimated their height (by 1.4 cm) and under-estimated their
      weight (by 1.7 kg). Using the self-report figures the prevalence of overweight/
      obese was 56.0% but this prevalence estimate increased to 65.3% when clinical
      measurements were used. The discrepancy in self-reported height and weight is
      partly explained by 1) a rounding effect (rounding height and weight to the
      nearest 0 or 5) and 2) older persons (65+ years) considerably over-estimating
      their height. CONCLUSION: Self-report is important in monitoring overweight and
      obesity; however, it must be recognised that prevalence estimates obtained are
      likely to understate the problem. IMPLICATIONS: The public health focus on
      obesity is warranted, but self-report estimates, commonly used to highlight the
      obesity epidemic, are likely to be underestimations. Self-report would be a more
      reliable measure if people did not round their measurements and if older persons
      more accurately knew their height.

PMID- 16800201
TI  - Canteen purchasing practices of year 1-6 primary school children and association
      with SES and weight status.
AB  - OBJECTIVE: To identify sources of food eaten during the school day, the types of
      foods and frequency of purchases from the canteen and association with SES and
      weight status in primary school-aged children. METHOD: This cross-sectional study
      was conducted in the Hunter region of New South Wales. Primary schools were
      randomly selected from a list of government schools and 5,206 students in years 1
      6 from the 16 participating schools were invited to participate in the study.
      RESULTS: Findings show the majority of children in the study bring their recess
      snack and lunch from home. However, the majority of children do use the school
      canteen and less healthy foods and high-sugar drinks are commonly purchased.
      CONCLUSIONS: This study confirms the relevance of the school canteen as a means
      of affecting children's eating habits. IMPLICATIONS: Improvement in the foods
      sold through schools provides an important contribution to model supportive
      environments for healthy food choices. Strategies should also be directed towards
      affecting the content of lunchboxes and the home environment.

PMID- 16800202
TI  - Cardiovascular mortality attributable to high blood cholesterol in New Zealand.
AB  - OBJECTIVE: To estimate mortality attributable to higher-than-optimal blood
      cholesterol in New Zealand in 1997, and the mortality burden that could be
      potentially avoided in 2011 if modest reductions in mean population blood
      cholesterol concentrations were achieved. DESIGN: Comparative risk assessment
      methodology was used to estimate the attributable and avoidable mortality due to
      higher-than-optimal total blood cholesterol (> 3.8 mmol/L). Disease outcomes
      assessed were deaths from ischaemic heart disease (IHD) and ischaemic stroke.
      RESULTS: Overall, higher-than-optimal blood cholesterol contributed to 4,721
      deaths in New Zealand in 1997 (17% of all deaths). This included 4,096 IHD deaths
      (64%) and 625 ischaemic stroke deaths (38%). Modest reductions in mean population
      blood cholesterol concentrations (e.g. 0.1 mmol/L) could potentially prevent 300
      deaths (261 IHD and 39 ischaemic stroke) each year from 2011. CONCLUSIONS: Higher
      than-optimal blood cholesterol concentrations are a leading cause of mortality in
      New Zealand. Modest reductions in blood cholesterol levels could have a major
      impact on population health within a decade.

PMID- 16800203
TI  - Folate intake and the primary prevention of non-neural birth defects.
AB  - OBJECTIVES: To investigate whether maternal periconceptional folate intake is
      associated with a reduction in selected non-neural birth defects in Western
      Australia (WA). METHODS: Case-control study of folate intake in women whose
      infants had orofacial clefts (62); congenital heart defects (151); urinary tract
      defects (117); limb reduction defects (26); or other major birth defects (119);
      and 578 control women. RESULTS: Neither folic acid supplements nor dietary folate
      intake in women not using supplements was significantly associated with a
      reduction in risk in any of the case groups. In contrast to neural tube defects,
      WA population data for orofacial clefts, heart defects, limb reduction defects
      and urinary tract defects showed no fall in prevalence since the introduction of
      folate promotion and voluntary food fortification. CONCLUSIONS: This study
      provides no evidence of folate being an important factor in the prevention of
      birth defects other than neural tube defects.

PMID- 16800204
TI  - Physical activity advice in the primary care setting: results of a population
      study in New Zealand.
AB  - OBJECTIVES: To determine the prevalence of physical activity advice, including
      the Green Prescription (a physical activity scripting scheme), given in the
      primary care setting, and the characteristics of New Zealanders who receive such
      advice. METHOD: Questions from a 2003 national postal survey (n = 8,291),
      'Obstacles to Action', were examined. The survey was designed to identify
      population segments to target for physical activity interventions. Binary
      logistic regression was used to examine independent factors associated with
      receiving a physician or practice nurse recommendation to increase physical
      activity and receiving a Green Prescription. RESULTS: Overall, 13.3% of the
      sample reported receiving physical activity advice while 3.0% reported receiving
      a Green Prescription from their general practitioner or practice nurse in the
      last year. Those more likely to receive physical activity advice were Maori or
      Pacific, overweight or obese, sedentary, or suffering chronic disease. Results
      were similar for Green Prescription advice. When controlling for these and other
      demographics, physical inactivity was not related to the odds of receiving a
      Green Prescription. CONCLUSIONS: One out of every eight New Zealanders reported
      being given general physical activity advice in the primary care setting. While
      the physically inactive but otherwise healthy were not specifically targeted, the
      Green Prescription was more likely to be given on the basis of existing chronic
      conditions related to physical inactivity and other high-risk populations.
      IMPLICATIONS: Primary care settings provide an important opportunity to promote
      physical activity for New Zealand adults. While those most at risk are more
      likely to receive such advice, there are many more that may benefit.

PMID- 16800205
TI  - Cervical spinal cord injury in rugby union and rugby league: are incidence rates
      declining in NSW?
AB  - OBJECTIVES: To estimate trends in incidence rates of rugby code-related severe
      cervical spinal cord injuries in New South Wales (NSW) from 1986 to 2003. To
      evaluate the Australian Spinal Cord Injury Register (ASCIR) for injury
      surveillance by comparison with two published studies. METHODS: Data were cases
      of complete and incomplete tetraplegia in rugby union and rugby league admitted
      to the two spinal units in NSW. Trends in incidence rates were estimated using
      Poisson regression modelling. RESULTS: There was a small, non-significant decline
      from 1986 to 2003 in the incidence rate of tetraplegia in rugby union (9.8 vs.
      6.1 per 100,000 player-years; p = 0.378) and rugby league (2.3 vs. 1.6 per
      100,000 player-years; p = 0.564). The most common causes of injury were scrums
      for rugby union (35%) and tackles for rugby league (78%). This did not change
      over time (rugby union, p = 0.118; rugby league, p = 0.288). The ASCIR identified
      more cases of tetraplegia than insurance claims data and at least 75% of the
      cases ascertained by medical record review. CONCLUSIONS: There remains an urgent
      need to further improve safety in rugby union and rugby league. Scrummage in
      union and tackles in league remain the leading causes of tetraplegia. Rates of
      tetraplegia were significantly higher and more variable in rugby union than in
      rugby league. IMPLICATIONS: The ASCIR is a useful tool to monitor trends in
      spinal cord injury incidence in both rugby codes. Its potential value is
      constrained by the lack of accurate estimates of player numbers.

PMID- 16800206
TI  - Reconsidering the role of a local diabetes society: patterns of membership in
      Christchurch, New Zealand.
AB  - OBJECTIVE: To investigate patterns of membership and barriers to service use in
      the Christchurch Diabetes Society. METHODS: A socio-economic profile of the
      Christchurch Diabetes Society's membership was constructed by examining the
      residential locations of society members in Christchurch City. Rates of
      membership by deprivation decile were calculated by comparing the membership data
      to the population of people diagnosed with diabetes. RESULTS: Persons living in
      deprived areas, in particular Maori and Pacific people, are under-represented in
      society membership. However, there is evidence that the relationship between
      ethnicity and membership rates is stronger in more deprived areas. CONCLUSIONS:
      This study provides further insights in understanding barriers to care and the
      role of NGOs. Given that groups in the community most likely to be affected by
      diabetes are least likely to be members of the society and to have access to the
      society's services, the results raise questions about the most appropriate role
      for local diabetes societies within a decentralised health system.

PMID- 16800207
TI  - The safety of edible fungi purchased at Melbourne markets.
AB  - OBJECTIVE: To determine if toxic mushroom species are sold at Melbourne fruit and
      vegetable markets. METHODS: We purchased a specimen of every mushroom on sale at
      six large Melbourne markets on four separate days evenly spread during the period
      April to June, 2005. These specimens were identified by a specialist mycologist
      at the Royal Botanic Gardens Melbourne. RESULTS: Ten edible mushroom species, but
      no toxic species, were identified. CONCLUSIONS: Mushrooms purchased from
      Melbourne markets appear to be safe. IMPLICATIONS: While this study provides no
      evidence that public health is at risk from mushrooms sold at Melbourne markets,
      it has important limitations. Ongoing periodic surveillance is warranted.

PMID- 16800208
TI  - Why do homeless young people leave home?
AB  - OBJECTIVE: To describe the reasons homeless young people leave home and
      differences between males and females. METHODS: Homeless young people between the
      ages of 12 and 20 years (n = 692) completed surveys conducted by trained
      interviewers using Questionnaire Delivery System on laptop computers as part of a
      large study. Participants indicated the importance of each of 22 reasons for
      leaving home on a four-point scale, from 'not important' (1) to 'very important'
      (4). RESULTS: Conflict with parents was the only reason reported as important by
      at least two-thirds of respondents. Desire for independence and/or adventure was
      rated as important by nearly one-half of young men and women. Eighteen reasons
      were rated as 'not or somewhat important' by most young people. These included
      issues associated with school, sexuality, sexual abuse and trouble with the law.
      Young women were more likely than young men to report that sexual abuse,
      anxiety/depression, and/or pregnancy were important reasons for leaving home. The
      converse held for personal alcohol and drug abuse, trouble with the police, and
      breach of community order or parole. With few exceptions, importance ratings of
      the 22 reasons were not highly correlated. CONCLUSIONS AND IMPLICATIONS: Service
      providers should consider how the diverse elements of family environment
      contribute to homelessness. A focus on familial problems may lead to other
      important reasons being overlooked, namely a desire for independence and
      adventure. Services and supports need to take into account whether young people
      leave home because of a life crisis or because they seek independence.

PMID- 16800209
TI  - An epidemic of infection, not just testing: chlamydia prevalence estimates in the
      Australian Capital Territory 1998-2004.

PMID- 16800210
TI  - Seasonal variation of participation in colorectal neoplasia screening by
      colonoscopy or CT colonography.

PMID- 16800211
TI  - Limited evidence supporting Legionella recommendation.

PMID- 16800212
TI  - Who attends skin cancer screening in the suburbs?

PMID- 16800213
TI  - Impact fever: what is it all about?

PMID- 16800214
TI  - Pre-test and post-test evaluation of students' perceptions of a collaborative
      clinical education model on the learning environment.
AB  - OBJECTIVE: This study investigated the impact of a collaborative clinical
      education model on students' perception of the psycho-social learning
      environment. DESIGN: A pre-test and post-test quasi experimental design. SETTING:
      A tertiary referral centre. SUBJECTS: Second and third year undergraduate nursing
      students were asked to rate their perceptions of the psycho-social learning
      environment at the completion of the clinical practicum. TOOL: The tool used to
      measure psycho-social perceptions of the clinical learning environment was the
      Clinical Learning Environment Inventory previously validated in Australian health
      care contexts. INTERVENTION: A collaborative arrangement with the university and
      ward staff where eight students are placed on a ward and a ward staff member is
      paid by the university to be 'off-line' from a clinical workload to supervise the
      students. This is in contrast to the standard facilitation model where students
      are placed with registered nurses in different localities under the supervision
      of a 'roving' registered nurse paid by the university. RESULTS: No significant
      differences were found in pre-test mean scores when comparing wards. Significant
      differences in post-test scores for the intervention group were identified in the
      sub scales of Student Involvement, Satisfaction, Personalisation and Task
      Orientation. CONCLUSIONS: The adoption of a collaborative clinical education
      model where students are integrated into the ward team and the team is
      responsible for student learning can positively enhance capacity for student
      learning during their clinical practicum.

PMID- 16800215
TI  - Clinical placements in residential aged care facilities: the impact on nursing
      students' perception of aged care and the effect on career plans.
AB  - OBJECTIVES: Undergraduate nursing students have often found clinical placements
      in aged care unsatisfactory and/or unsettling, dissuading them from considering
      aged care as an employment option on graduation. This study asked which elements
      of the clinical placement experience produced that outcome; and what changes
      could yield more positive outcomes. DESIGN: A descriptive qualitative pilot study
      was carried out in late 2003. A combination of nominal groups and semi-structured
      interviews was used with students and experienced nurses to identify
      commonalities and variations in issues nominated as important and in the views
      expressed on those issues. Transcripts were independently analysed by two
      experienced investigators. Themes identified were discussed among the
      researchers. SUBJECTS: Fourteen volunteer undergraduate nursing students, all of
      whom had completed clinical placements in residential care and some of whom had
      prior experience in such facilities, participated in the nominal groups. Twelve
      registered nurses who had acted as clinical teachers in aged care facilities were
      interviewed. RESULTS: Perceived issues included: unexamined assumptions about
      nursing's core skills; lack of pre-placement orientation to the residential care
      environment; the appeal of and apprehension aroused by autonomous practice; and
      status, income and career progression considerations. CONCLUSIONS: Analysis of
      the sometimes ambivalent and conflicting views expressed pointed to possible
      changes, all within the domain of training and employing institutions, capable of
      bringing submerged issues to the surface for examination and resolution as part
      of raising student understanding of gerontology as a demanding specialty and
      residential care as a rewarding career.

PMID- 16800216
TI  - The attitudes and practices of neonatal nurses in the use of kangaroo care.
AB  - OBJECTIVES: To survey the attitudes and practices of Australian neonatal nurses
      in the use of kangaroo care (KC) and identify possible concerns with promoting KC
      in the neonatal intensive care unit (NICU). DESIGN: A two-phase research approach
      was used that included a descriptive survey followed by in-depth interviews with
      a subset of survey respondents. SAMPLE: Thirty four nurses working in the NICU of
      a large public hospital in Melbourne completed a survey questionnaire. Four
      respondents were subsequently selected for follow-up interview to explore in
      greater depth issues associated with promoting KC in the NICU. OUTCOME MEASURES:
      Quantitative data were analysed to describe the attitudes, practices and role of
      the neonatal nurse in promoting KC. Analysis of qualitative responses to survey
      questions and interviews were coded and major themes identified. RESULTS: All
      neonatal nurses surveyed assisted and encouraged parents to provide KC and the
      majority agreed on the benefits of KC for both infant and parents. There was a
      general acceptance that KC can be practiced with low birth weight infants
      requiring intubation and all but two nurses found facilitating KC professionally
      satisfying. Results also identified practical concerns with the practice of KC
      and some uncertainty that KC promotes breastfeeding. Notable constraints to
      promoting KC in the NICU were heavy staff workloads, insufficient education, lack
      of organisational support and the absence of clear protocols, especially for low
      birth weight infants. CONCLUSIONS: This study confirms neonatal nurses strongly
      support the use of KC in the NICU. Although the majority of nurses reported
      positive attitudes and practices, they did identify a number of educational and
      practical concerns that need to be addressed to ensure KC with low birth weight
      infants is safe and effective.

PMID- 16800217
TI  - The effectiveness of a 15 minute weekly massage in reducing physical and
      psychological stress in nurses.
AB  - OBJECTIVE: To investigate the effectiveness of massage therapy in reducing
      physiological and psychological indicators of stress in nurses employed in an
      acute care hospital. DESIGN: Randomised controlled trial. SETTING: Acute care
      hospital in Queensland. SUBJECTS: Sixty nurses were recruited to the five week
      study and randomly assigned to two groups. INTERVENTION: A 15 minute back massage
      once a week. The control group did not receive any therapy. MAIN OUTCOME
      MEASURES: Demographic information, a life events questionnaire and a brief
      medical history of all participants was completed at enrolment. Physiological
      stress was measured at weeks one, three and five by urinary cortisol and blood
      pressure readings. Psychological stress levels were measured at weeks one and
      five with the State-Trait Anxiety Inventory (STAI). RESULTS: Differences in the
      change in urinary cortisol and blood pressure between the two groups did not
      reach statistical significance. However, STAI scores decreased over the five
      weeks for those participants who received a weekly massage. The STAI scores of
      the control group increased over the five week period. These differences between
      the groups were statistically significant. CONCLUSION: The results of this study
      suggest that massage therapy is a beneficial tool for the health of nurses as it
      may reduce psychological stress levels. It is recommended that further large
      studies be conducted to measure the symptoms of stress rather than the
      physiological signs of stress in nurses.

PMID- 16800218
TI  - Hospital in the home (HITH) care following autologous stem cell transplantation
      for lymphoma and multiple myeloma.
AB  - BACKGROUND: Advances in outpatient and supportive care and increased pressure on
      hospital bed usage has led to the investigation of hospital in the home (HITH)
      management following autologous haematologous stem cell transplantation
      (AutoHSCT) for patients with multiple myeloma or lymphoma. DESIGN: The Newcastle
      Mater Hospital Haematology Unit together with the Mater Acute Care Community
      Service (MACCS) developed a protocol for HITH care following AutoHSCT. OUTCOMES:
      Clinical outcomes of the protocol were audited: 40% (13) of patients were
      suitable candidates for HITH care post transplantation. Of these 84.6% (11) were
      readmitted to the haematology unit within seven days of discharge from hospital.
      CONCLUSION: Our preliminary experience suggests that with adequate infrastructure
      support and rigorous patient selection this model of care is both safe and
      feasible.

PMID- 16800219
TI  - Trialing collaborative nursing Models of Care: the impact of change.
AB  - OBJECTIVE: The aim of the project was to develop and trial a nursing Model of
      Care (MoC) and devise a framework to investigate the impact of nursing staff mix
      on patient outcomes and job satisfaction (nurses). SETTING AND SUBJECTS: In 2001
      2002 a pilot project was undertaken to explore issues related to the delivery of
      patient care by nurses on two medical inpatient wards, one acute and one
      subacute, at a referral teaching hospital in New South Wales (NSW), Australia.
      The framework employed was an adaptation of, and based on, the Clinical Practice
      Improvement (CPI) model developed by NSW Health. PRIMARY ARGUMENT: Countries
      across the world are seeking solutions to a shortage of registered nurses and
      their ability to sustain quality care services. It becomes imperative that
      organisations develop strategies to attract and retain nurses in the health care
      system. CONCLUSIONS: Results of the project highlighted areas related to the
      quality of care delivery: clinical supervision; continuity of staffing; trust;
      employer of choice; more effective nurse to patient ratios; educational
      preparation; and recognition of prior experience.

PMID- 16800220
TI  - Developing the future nurse leaders of Fiji.
AB  - BACKGROUND: Nurse leaders in Fiji are currently involved in meeting the
      challenges of being at the forefront of an AusAID supported Health Sector
      Improvement process. Fiji is experiencing the same shortages of health
      professionals (including nurses) as is occurring internationally, while
      simultaneously striving to improve the quality of its health services. PRIMARY
      ARGUMENT: This paper provides information about the current situation in relation
      to health services in Fiji, and describes strategies being undertaken by the
      nurse leaders of Fiji to meet the challenge of leading an exciting reform
      process. James Cook University, School of Nursing Sciences, has been privileged
      to support the provision of contemporary leadership and management education for
      current and future nurse leaders in the Fiji Health Sector as a component of a
      current education program to educate registered nurses to bachelor level. This
      paper will provide an overview of the current Fiji Health Sector Improvement
      Program, with a particular focus on the preparation of nurse leaders. CONCLUSION:
      There is an ongoing need to understand beliefs and values, and styles of
      interaction and communication, and indeed, ideas about time. With collaboration
      between Australian academics and Fiji tutors from the Fiji School of Nursing, the
      program appears to be remarkably successful.

PMID- 16800221
TI  - "The Anaesthetist" 1933--an iconic Australian medical photograph.
AB  - Harold Cazneaux was the greatest Australian photographer of the early 20th
      century. In 1933, he took this image entitled 'The Anaesthetist'. It is an
      important documentation of a clinical anaesthetist of the era and was exhibited
      internationally. Such photographs of specific medical scenarios are rare and
      valuable. The anaesthetist is Dr Frederick J. Bridges who worked at Royal Prince
      Alfred and Royal North Shore Hospitals in Sydney. He is using a Clements ether
      vaporizer which was Australian made. The patient is Cazneaux's daughter Cazneaux
      has captured perfectly the care and concern of the anaesthetist for his patient.

PMID- 16800222
TI  - Some observations on early military anaesthesia.
AB  - Although anaesthesia was discovered in 1846, pain relief had been used for many
      years previously. Opium, mandragora, and Indian hemp amongst others have been
      used since the earliest times as alluded to by many of the classical writers. The
      use of refrigeration anaesthesia is known to have been recommended a millennium
      ago although it never had much usage. Very soon after the introduction of ether
      anaesthesia, it was recommended for military use and the first use by the
      American forces was in Buena Vista early in 1847 and then again at Vera Cruz.
      Pirogoff taught and used ether anaesthesia on active service with the Russian
      forces in the Caucasus in the summer of 1847. Meanwhile Spencer Wells, who was
      serving with the Royal Navy in Malta, was the first British service medical
      officer recorded to have used anaesthesia. He went on to write up a series of 106
      anaesthetics. The Danes were probably next to use anaesthesia in battle using
      chloroform in 1848. However, it was not until the Crimean War that anaesthesia
      began to play an important part in battle surgery with many anaesthetics being
      given with varying results. The War of the Rebellion was the next war in which
      anaesthesia was important and the first one in which proper statistics were kept
      allowing useful analysis. Anaesthesia had irrevocably found its place in
      battlefield surgery.

PMID- 16800223
TI  - Brian Dwyer and the St. Vincent's Pain Clinic 1962 to 1989.
AB  - Brian Dwyer was the Director of the Department of Anaesthetics at St. Vincent's
      Hospital in Sydney from 1955 to 1985. He developed a major interest in the
      management of intractable pain and was most impressed by the multidisciplinary
      pain clinic which was commissioned at the University of Washington in Seattle by
      John Bonica in 1960. In August 1962, Dr Dwyer established the first pain clinic
      in Australia, based on the Seattle model. Initially the St. Vincent's Pain Clinic
      specialized in the management of pain of malignant origin but in the 1970s and
      1980s the work expanded to include the treatment of pain arising from a variety
      of benign conditions. The great strengths of the Pain Clinic were its
      multidisciplinary approach to pain problems and the realisation of the importance
      of psychological factors in the persistence of pain. As a result of his work,
      Brian Dwyer received international recognition as a pioneer in the field of
      chronic pain management and the St. Vincent's Pain Clinic served as a model for
      the establishment of similar units, both in Australia and overseas. Brian Dwyer
      was the first chairman of the Clinic and remained in that position until his
      retirement in 1989.

PMID- 16800224
TI  - The early development of intravenous apparatus.
AB  - Modern anaesthetists rely on the intravenous route for administration of drugs
      and fluids. This paper traces the development of intravenous equipment from the
      first, tentative experiments with the intravenous route through to the first
      intravenous cannulas.

PMID- 16800225
TI  - The introduction of halothane into clinical practice: the Oxford experience.
AB  - This paper reviews the clinical situation in anaesthesia before the introduction
      of halothane into clinical practice in 1956, emphasising the limitations of
      agents available at the time. The background to the development of halogenated
      hydrocarbon compounds as anaesthesia agents is presented, including the
      involvement of Imperial Chemical Industries in England. The Nuffield Department
      of Anaesthetics was involved in the clinical trials and the designing and
      execution of these. The results of their work and the problems encountered are
      presented.

PMID- 16800226
TI  - The inventors.
AB  - Amongst Australian anaesthetists there have been many whose ingenuity and
      mechanical knowledge produced ingenious devices. Lidwill and Geoffrey Kaye come
      immediately to mind, and their contributions are well-described elsewhere. In
      this paper, two inventions with contrasting fates are described: the Grant
      Humidifier and the Komesaroff single-use analgesia device. Graham Grant's
      invention addressed the problem of rain-out in a most ingenious manner The device
      was compact, efficient and deserved greater commercial success, but a similar
      apparatus developed in New Zealand was better supported and captured most of the
      market. Grant has a degree in engineering, acquired before his medical degree,
      but David Komesaroff spent only a year in the Engineering Faculty before
      transferring to Medicine. Nevertheless, he has remained interested and in touch
      with technical matters, and has a number of other devices to his credit. Mention
      is briefly made of others: Stokes (of the suction bullet), Bill Cole (an early
      volatile specific vaporiser), Fisk (the paediatric ventilator) and Noel Cass (the
      Cass needle) These achievements are by no means the end of the road. Already an
      Australian-designed single-use laryngoscope is being manufactured and launched on
      both the national and international markets.

PMID- 16800227
TI  - The contribution of newspapers and their advertisements to the history of
      colonial anaesthesia.
AB  - The first news to reach New Zealand about the beneficial effects of inhalation of
      ether during surgical operations arrived in Wellington on Sunday July 4 1847.
      This was 283 days after the first successful demonstration in Boston. The mail
      services that brought this news and the original source of this news are
      described. After this news had reached Wellington, it then took another 84 days
      before the first successful trial of the agent took place in the recently opened
      Wellington Colonial Hospital. This period of eighty-four days compares
      unfavourably with those for Sydney and Cape Town. The reasons for this delay are
      discussed and using information available in the local Sydney and Wellington
      newspapers, the delay is shown to have been due to the unavailability of supplies
      of the necessary chemical reagents.

PMID- 16800228
TI  - Risk factors associated with Brachyspira hyodysenteriae PCR-positivity in East
      European pig production units.
AB  - The objective of the present study was to determine the risk factors for swine
      dysentery in East-European middle-to-large sized, farrow-to-finish units, with
      separate breeding and grower-finisher facilities. Samples of faeces from 10
      breeding animals (3-10% of the female inventory) and 10 grower finisher pigs (80
      140 days of age) were collected for polymerase chain reaction testing (PCR) for
      Brachyspira hyodysenteriae (B. hyo). Of 139 farrow-to-finish units, 51 (36.7%)
      were positive, 49 (35.3%) were negative, and 39 (28.1%) were inconclusive for B.
      hyo by PCR. In breeding subunits, twelve variables passed the screening criterion
      for risk factors (P < .2) for B. hyo PCR positivity. The odds of the breeding
      subunits being B. hyo PCR positive were 3.5 times greater when the grower
      finisher subunit was positive and the fibre content of the diet was > 6%. Use of
      'all-in-all-out' farrowing policy and having >60% multiparous sows each reduced
      the odds of being B. hyo PCR-positive by 4-fold. In grower-finisher subunits,
      fourteen variables passed the screening criterion for risk factors (P < .2) for
      B. hyo PCR positivity. B. hyo PCR-positive status of the breeding subunits and
      higher fibre content of the diet were the most influential variables, with the
      odds of the grower-finisher subunits being B. hyo PCR positive being almost 8
      times greater when the breeding subunit was also B. hyo PCR positive. Grower
      finisher B. hyo PCR positivity was also associated with the percentage of pigs
      housed on concrete slats, with the odds of being positive being 7.5-times higher
      for subunits where more that 70% of the animals were kept on concrete slats
      compared with all other floor types. There was a strong association between
      grower-finisher status and whether the animals were on outdoor lots, with the
      odds of being B. hyo PCR positive being substantially lower for pigs on outdoor
      lots compared with all other surfaces. IN CONCLUSION: All-in-all-out management
      in the breeding units, B. hyo negativity of adjacent grower-finisher units, high
      fibre content of the diet, and older parity structure in a sow herd may reduce
      the risk of swine dysentery. In grower-finisher units, slatted flooring is
      associated with a higher risk, while B. hyo negativity of the breeding units, the
      fibre content of the diet, and outdoor production are associated with lower risk
      of swine dysentery.

PMID- 16800229
TI  - [Stung by the wasps?].

PMID- 16800230
TI  - [Veterinary business in Dutch missionary areas].

PMID- 16800231
TI  - [Life down under. Experiences of a Dutch cattle veterinarian in New Zealand].

PMID- 16800232
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Sperm cryopreservation].

PMID- 16800233
TI  - [The end of a partnership is coming. How do we proceed?].

PMID- 16800234
TI  - [High or low value added taxes, a clarification].

PMID- 16800235
TI  - [An interesting horse program at the Voorjaarsdagen, part II].

PMID- 16800236
TI  - [Symposium on advances in feline medicine].

PMID- 16800237
TI  - [Congress research makes teacher].

PMID- 16800238
TI  - [Professional integrity theme Year Congress 2006].

PMID- 16800239
TI  - Influenza viruses in general, human strains, shift and drift, vaccination.

PMID- 16800240
TI  - Avian influenza in swine: a threat for the human population?
AB  - Until recently, it was thought that pigs were required as intermediate hosts for
      the transmission of avian influenza viruses to humans and this hypothesis is
      based on three suppositions: (1) Pigs are more susceptible to avian influenza
      viruses than humans. (2) Pigs are the single animal species with receptors
      preferred by both avian (alpha 2-3 linked sialic acid to galactose) and human
      (alpha 2-6 linked sialic acid) influenza viruses, which supports their role as
      "mixing vessels" for reassortment between human and avian viruses. In addition,
      influenza viruses from aquatic birds can adapt to "human" receptors in the pig.
      (3) Genetic reassortment between avian and human influenza viruses, which is an
      important mechanism for the emergence of new pandemic human strains, frequently
      occurs in pigs in nature. The first part of this paper presents some critical
      (counter) arguments for these suppositions. The second part focuses on the role
      of swine in recent cases of highly pathogenic avian influenza (HPAI) in humans in
      The Netherlands and in Southeast Asia. The respective HPAI viruses have spread
      directly from infected poultry to both humans and pigs, and pigs did not serve as
      an intermediate host between birds and humans. Fortunately, it is unlikely that
      these viruses would spread widely in the human population, unless mutations or
      genetic reassortment would occur. In theory such genetic changes might occur in
      the pig. However, it is currently impossible to analyse the risk of the pig in
      the introduction of new avian influenza strains in the human population, because
      the basic questions about the replication and pathogenesis of such viruses in
      swine are still unanswered.

PMID- 16800241
TI  - Avian influenza: mini-review, European control measures and current situation in
      Asia.
AB  - Avian influenza (AI) is a highly contagious disease for birds, which can easily
      take epidemic proportions when appropriate and efficacious measures are not taken
      immediately. Influenza viruses can vary in pathogenicity from low to medium or
      highly pathogenic. A low pathogenic strain can become highly pathogenic by
      introduction of new mutations (insertions, deletions or substitutions) in the
      cleavage site of the haemagglutinin during circulation in chickens. Up till now
      only H5 and H7 strains gave rise to highly pathogenic strains in this manner. At
      present the avian H5N1 influenza virus is endemic in Southeast Asia (47) and is
      expanding westward. In addition, its virulence is extremely higher than other
      HPAI, like H7N7. Moreover, the avian host range is expanding, as species
      previously considered resistant, now get infected and can contribute to the
      dissemination of the virus. In the context of H5N1, all movements (trade, high
      international mobility, migration and smuggling) can become high risk factors of
      spreading the disease. In most European countries eradication measures are
      applied when an outbreak occurs. But such measures have great economical and
      social implications, and are no longer generally accepted. The combination of
      prophylactic measures (vaccination and medicines), hygienic measures and
      surveillance could offer an acceptable alternative.

PMID- 16800242
TI  - Influenza virus inhibitors available for the chemotherapy and/or chemoprophylaxis
      of influenza virus infections.
AB  - There are, at present, only three (classes of) compounds that could be considered
      for the chemotherapy and -prophylaxis of influenza virus infections: ribavirin,
      amantadine/rimantadine and the neuraminidase inhibitors zanamivir and
      oseltamivir. The latter, also known under the registered name of Tamiflu, seems
      to be the most indicated, as it is effective against influenza A and B virus
      infections and can be conveniently administered orally in capsule form (twice
      daily). In the wake of a potential influenza A virus pandemic it may be advisable
      to have at hand sufficient amounts of oseltamivir to affront such emerging
      infection.

PMID- 16800243
TI  - [Recommendation of the Royal Academy for Medicine of Belgium to the responsible
      policy authorities in connection with the continually increasing threat of an
      outbreak of an influenza epidemic].
AB  - In two of its regular sessions, the Royal Academy for Medicine of Belgium
      consulted with influenza experts on the current threat of a severe pandemic
      outbreak, and in particular on the eventuality that this outbreak may be caused
      by a virus identical or related to the avian influenza virus H5N1. On the basis
      of this consultation, the Academy issued an advisory statement to the Belgian
      federal and Flemish regional Health Authorities. The Academy shares the experts'
      concern that the forthcoming influenza pandemic may well affect a larger part of
      the population than previous pandemics in 1958, 1968 and 1977. The Academy found
      it satisfying that the Belgian government is developing an appropriate pandemic
      containment plan. A primary objective of the plan is to safeguard general health
      care during the pandemic. Availability of staff and infrastructure and continuity
      of medical supplies must by all means remain intact. Therefore, employees in
      these sectors are an important target group of preparatory actions, in particular
      briefing about, and field rehearsals of the containment plan. Health care
      workers, elderly people and the chronically ill constitute a priority group
      eligible for vaccination with the antigens of the pandemic virus and for the
      administration of virus inhibitors. The effectiveness of antiviral treatment and
      prophylaxis during a pandemic is, given the lack of experience, uncertain. The
      fact that such remedies will be available must not create a false sense of
      security and must certainly not lead to reduced alertness with regard to the
      preparation and implementation of other measures. Panic reactions among the
      population must be avoided. Therefore, the population must be informed in due
      course about appropriate ways of conduct when a pandemic strikes, e.g.
      recognition of the early signs of influenza, the need to consult a general
      practitioner at once, the reason why being nursed at home is to be preferred to
      being hospitalized, etc. Indifference towards vaccination must be overcome. In
      the period prior to the pandemic people must be encouraged to obtain vaccination
      against the prevalent interpandemic virus strains. Belgium does not stand alone
      in the avian influenza threat and can largely benefit from participating in the
      current international initiatives to co-ordinate measures.

PMID- 16800244
TI  - Ovarian cancer stage IIIC. Consequences of treatment level on overall and
      progression-free survival.
AB  - BACKGROUND: Maximum cytoreduction at primary surgery has been found to be one of
      the strongest prognostic factors for survival of ovarian cancer. The aim of the
      study was to investigate the influence of hospital level (primary vs secondary
      care centre), number and timing of surgery and chemotherapy on how radical the
      surgery was at primary treatment of epithelial ovarian cancer Stage IIIC.
      MATERIAL AND METHODS: A retrospective study based on record information from all
      patients with epithelial ovarian cancer Stage IIIC treated at the Norwegian
      Radium Hospital (NRH) 1985-2000, in total 776, subdivided into four groups: 1)
      Local primary surgery, no direct re-operation at NRH, no interval debulking; 2)
      local primary surgery, no direct re-operation, but interval debulking after 3-4
      courses of chemotherapy at NRH; 3) local primary surgery, direct re-operation at
      NRH, no interval debulking; 4) primary surgery at NRH. Lymph node biopsies at re
      operation in early stages and upgrading of stage where necessary were registered.
      RESULTS: Whether surgery was radical or not was an independent prognostic factor
      for overall and progression-free survival. The treatment group was an independent
      prognostic factor for overall, but not for progression-free survival. Group 3 had
      significantly the best overall and progression-free survival (p = 0.01 and 0.05).
      For macroscopically radical surgery both overall and progression-free survival
      were found significantly better for groups 3, 4 and 1 than for group 2. Most
      lymph node biopsies were performed during the last period and 28% were upgraded
      from Stage I and II to IIIC. More patients were referred for primary surgery at
      NRH during the last 5-year period during which overall survival and time to
      progression were significantly better. INTERPRETATION: Whether primary surgery is
      radical or not is a significant prognostic factor for survival and primary
      surgery is best performed by specialists in gynaecological oncology.

PMID- 16800245
TI  - Down-regulation of E-cadherin is closely associated with progression of cervical
      intraepithelial neoplasia (CIN), but not with high-risk human papillomavirus
      (HPV) or disease outcome in cervical cancer.
AB  - OBJECTIVE: E-cadherin plays a pivotal role in maintenance of normal adhesion in
      epithelial cells but has also been shown to suppress tumour invasion and
      participate in cell signalling. Known to be capable of reversing the invasive
      phenotype of high-risk human papillomavirus (HPV)-transformed keratinocytes, E
      cadherin is down-regulated in CIN and cervical cancer (CC), but still
      incompletely studied as an intermediate endpoint marker in this disease. MATERIAL
      AND METHODS: As part of our HPV-PathogenISS study, a series of 150 CCs and 152
      CIN lesions were examined using immunohistochemical (IHC) staining for E
      cadherin, and tested for HPV using PCR with three primer sets (MY09/11, GP5+/GP6,
      SPF). Follow-up data were available from all squamous cell carcinoma (SCC)
      patients, and 67 CIN lesions were monitored with serial PCR for HPV after cone
      treatment. RESULTS: Expression of E-cadherin was reduced in parallel with the
      increasing grade of CIN, with major down-regulation upon transition to CIN3 and
      further to invasive cancer (OR 6.95; 95% CI 2.67-18.09) (p = 0.0001). Negative
      markedly reduced E-cadherin expression was a 90.9% specific indicator of CIN,
      with 97.4% PPV, but suffered from low sensitivity (27.0%) and NPV (9.1%). E
      cadherin expression was completely unrelated to HR-HPV (p = 0.982), and did not
      predict clearance/persistence of HR-HPV after treatment of CIN. Similarly, E
      cadherin expression was not a prognostic predictor of CC in univariate or
      multivariate analysis. CONCLUSIONS: Down-regulation of E-cadherin was closely
      associated with progressive CIN and cell proliferation. It is tempting to
      speculate that part of this cell proliferation is mediated through the canonic
      Wnt signalling pathway, after liberation of transcriptionally competent beta
      catenin from the E-cadherin/catenin complex, most notably orchestrated by E6 and
      E7 oncoproteins of HR-HPV. Such a liberation of beta-catenin would abrogate the
      negative transcriptional control of E-cadherin on the Lef/TCF/beta-catenin
      responsive genes. The exact role of HR-HPV oncoproteins E6 and E7 in this process
      remains to be seen in future studies.

PMID- 16800246
TI  - Breast cancer treatment--later pregnancy and survival.
AB  - Although breast cancer (BC) affects patients at older age, it occurs more
      frequently in premenopausal women due to better diagnostic methods and an
      increasing trend towards delay in childbearing. The increasing population of
      women with BC delaying childbearing may be of concern regarding the effect of
      treatment on later pregnancy, as well as the influence of pregnancy on the
      prognosis of disease and survival. Radiotherapy has shown no adverse effects on
      the clinical outcome in the offspring except diminished lactation. The offspring
      of patients who became pregnant after chemotherapy have shown no congenital
      anomalies, although sometimes a high abortion rate (10-29%) has been
      demonstrated. Currently, several fertility-sparing options, including the use of
      endocrine therapy and assisted reproductive technologies, cryopreservation and
      ovarian tissue transplantation, are very promising. The survival of BC patients
      is not decreased by a subsequent pregnancy; compared with the non-pregnant group
      their survival rates are often the same or better, with favourable relative risks
      and lower recurrence of metastases.

PMID- 16800247
TI  - Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high
      risk cervical cancer: long-term follow-up.
AB  - INTRODUCTION: Chemo-potentiation of radiation improves survival in women with
      cervical cancer. Our group has previously demonstrated the tolerability of weekly
      paclitaxel combined with cisplatin during radiation therapy. We sought to
      determine the efficacy of this regimen in patients with "high risk" cervical
      cancer, and to determine the short- and long-term toxicity of this approach.
      METHODS: We prospectively enrolled surgically staged patients with positive
      peritoneal cytology, resectable nodal metastases, or primary tumor > 6 cm.
      Patients were treated using external beam radiation with concomitant cisplatin
      (50 mg/m2) during weeks 1, 4, and 7, and weekly paclitaxel (50 mg/m2), followed
      by four courses of adjuvant cisplatin (50 mg/m2) and paclitaxel (135 mg/m2).
      Toxicity, overall, and disease-free survival were evaluated. RESULTS: Twenty
      three patients were enrolled, and 21 were evaluable. Patient allotment by FIGO
      stage was: IB1 - seven, IB2 - five, IIA - two, IIB - four, IIIB - two, IV -
      three. Twenty patients (95%) completed radiation treatment (median dose to point
      A was 8278 cGy). Seventeen patients (81%) completed all chemotherapy. At a median
      follow-up of 58 months the overall survival was 68%. Overall survival for
      patients with clinical Stage I and II disease was 82% at a median of 64 months.
      Hematologic toxicity was common but rarely resulted in treatment delays. Late
      complications requiring intervention (obstruction, fistula, significant
      lymphocyst) occurred in 11 patients (52%). CONCLUSION: The combination of
      paclitaxel and cisplatin appears efficacious in "high-risk" cervical cancer
      patients. Hematologic toxicity was common but tolerable. Long-term survival was
      common in these patients, however late toxicity was significant. This regimen
      should be investigated in collaborative phase III trials.

PMID- 16800248
TI  - Radioguided occult lesion localisation in combination with detection of the
      sentinel lymph node in non-palpable breast cancer tumours.
AB  - PURPOSE OF THE INVESTIGATION: The aim of study was to determine the efficacy of
      radioguided occult lesion localisation (ROLL) for non-palpable invasive breast
      cancer combined with sentinel lymph node biopsy (SLNB) and to compare the amount
      of tissue excised by radioguided navigation versus the hook-wire technique.
      METHODS: We injected 45 MBq of radiolabelled technetium intratumourally and 15
      MBq subdermally 18 hours before surgery in 21 women with bioptically verified non
      palpable breast cancer. We identified by gamma probe non-palpable tumours, which
      were excised, followed by identification and excision of the sentinel lymph node.
      We compared our results with a group of 12 women with non-palpable lesions marked
      by hook-wire localisation. RESULTS: ROLL combined with SLNB was successful in
      100%; volume of excised tissue was smaller in the hook-wire group but expressed
      higher variability in volume than in the ROLL group although the difference was
      not statistically significant. CONCLUSION: The method of ROLL combined with SLNB
      is technically possible and safe, resulting in minimisation of the surgical
      intervention and a decrease in postoperative morbidity. ROLL was more precise
      than the hook-wire procedure even though the amount of tissue excised was the
      same in both groups.

PMID- 16800249
TI  - Efficiency of three surgical procedures in eliminating high-risk human
      papillomavirus infection in women with precancerous cervical lesions.
AB  - PURPOSE OF INVESTIGATION: To establish the efficiency of laser vaporization (LV),
      large loop excision of the transformation zone (LLETZ) and cold knife conization,
      done for precancerous cervical lesions, in eliminating high-risk human
      papillomavirus (HPV) infection. Additionally, we determined whether the same HPV
      genotype persisted after surgery. METHODS: A total of 214 women were tested for
      HPV infection by the Hybrid Capture II (HCII) test prior to surgery. HPV-positive
      women were followed by HCII test ten months after surgery. In persistently HPV
      positive women, HPV genotypes were determined by PCR - PGMY09/PGMY11. RESULTS:
      The HCII test showed elimination of HPV infection after LV, LLETZ and cold knife
      conization in 67.6%, 86.3%, and 100% (p < 0.05) of women, respectively. In seven
      (38.9%) women a different HPV genotype was found to be present after surgery, the
      corrected efficiency thus being 79.4%, 92.7% and 100% (p = NS), respectively.
      CONCLUSIONS: The three analyzed surgical procedures are effective in eliminating
      high-risk HPV infection. HPV testing is useful at follow-up, since it can
      identify a small proportion of women requiring close surveillance and potential
      treatment.

PMID- 16800250
TI  - Effective chemoradiotherapy protocol with 5-fluorouracil for cervical squamous
      cell carcinoma in vitro.
AB  - PURPOSE OF INVESTIGATION: 5-Fluorouracil (5FU) is frequently used in concurrent
      chemoradiotherapy for patients with advanced cervical cancer, although its
      optimal chemoradiotherapy protocol has not yet been established. In search of an
      optimal chemoradiotherapy protocol, some in vitro experiments were carried out.
      METHODS: The radiosensitive human cervical squamous cell carcinoma cell line
      ME180 was examined to investigate the effects of 5FU on radiosensitivity and the
      effects of irradiation on 5FU-sensitivity. RESULTS: 5FU dose-dependently enhanced
      cellular radiosensitivity at therapeutic concentrations. Although high doses of y
      ray irradiation significantly reduced the 5FU-sensitivity, a low dose of
      irradiation at therapeutic doses (< 2.5 Gy) had no effect on 5FU-sensitivity of
      the irradiated cells. Cells pretreated with 5FU eight hours before irradiation
      showed significantly higher 5FU-sensitivity than cells concurrently treated with
      5FU and irradiation. In contrast, cells treated with 5FU eight hours after
      irradiation showed significantly lower 5FU-sensitivity than cells concurrently
      treated with 5FU and irradiation. Moreover, all four post-irradiation surviving
      subclones obtained from repeatedly irradiated ME180 cells showed significantly
      lower 5FU-sensitivity than the non-irradiated parent cells. CONCLUSION: 5FU acts
      as a radiosensitizer for cervical squamous cell carcinoma and 5FU-sensitivity is
      reduced in irradiated cells. Therefore, 5FU administration immediately before
      irradiation may be a more effective treatment than concurrent chemoradiotherapy
      or post-irradiation chemotherapy with 5FU.

PMID- 16800251
TI  - Trastuzumab in metastatic breast cancer.
AB  - Metastatic breast cancer is an incurable disease in a very high percentage of
      patients. Despite new progress in endocrine and other systemic therapies, this
      evidence remains challenging for patients and clinicians. HER2 protein is a
      member of the epidermal growth factor family of transmembrane receptors. HER2 is
      overexpressed in approximately 20% to 30% of breast cancers. Overexpression of
      HER2 has been shown to be associated with increased tumor proliferation and
      relative resistance to some types of chemotherapy and hormonal therapies.
      Trastuzumab, a humanized monoclonal antibody directed against HER2 protein, has
      been shown to be an efficacious and well tolerated treatment for HER2
      overexpressing metastatic breast cancer, both as a single agent and when it is
      used in combination with chemotherapy.

PMID- 16800252
TI  - Clinicopathological features of unusual vascular lesions of the pelvis,
      retroperitoneum and colon in females: a report of five cases and review of the
      literature.
AB  - Vascular lesions comprise benign and malignant neoplasms as well as non
      neoplastic conditions that may be located in various sites but only rarely in the
      pelvis or the retroperitoneum. In our study we describe five diverse and unusual
      cases of vascular lesions of the pelvis, retroperitoneum and colon in female
      patients: a case of retroperitoneal angiosarcoma, pelvic hemangioendothelioma,
      pelvic angiomyxoma, retroperitoneal lymphangioleiomyomatosis and a case of
      diffuse cavernous hemangiomatosis of the colon, with emphasis on their
      clinicopathological features and differential diagnosis. The recent literature on
      the subject is also briefly reviewed.

PMID- 16800253
TI  - Proliferative effects of different hormone regimens on mammary glands in
      ovariectomized rats.
AB  - OBJECTIVE: To compare the proliferative effect of different hormone regimens and
      estrogen receptor modulation on mammary glands in a rat model of surgical
      menopause. DESIGN: Experimental animal study. SETTING: University Hospital.
      INTERVENTION: In a rat model of surgical menopause, 78 adult Sprague Dawley
      female rats were ovariectomized and treated with estrogen, estrogen combined with
      continuous or intermittent progesterone or the estrogen receptor modulator
      raloxifene and their respective vehicle controls. Following intraperitoneal drug
      administration for 20 days, rats were perfused, mammary glands were removed,
      tissues were processed for immunohistochemical (Ki-67) and hematoxylin-eosin
      staining, and investigated under light microscope. MAIN OUTCOME MEASURE:
      Histopathological examination of mammary glands and Ki-67 positive cells
      (proliferation index). RESULTS: Histological examination showed dilatation in the
      duct cysts and vacuolization in the epithelial cells in groups receiving
      progestin, either intermittent or continuous. Histological findings in the
      raloxifene group were no different from the control group, and the atrophic
      terminal ductal lobular unit in adipose tissue rich stroma was similar to
      postmenopausal breast. In animals with a proliferative response, increased
      proliferation started and dominated in the terminal ductal lobular unit
      epithelium. Comparison of Ki-67 proliferation indices between groups revealed
      that estrogen alone or combined with intermittent progesterone yielded
      significantly higher Ki-67 indices compared to controls; estrogen combined with
      continuous progesterone also resulted in increasing the probability of
      proliferation, but the effect was not as pronounced as the other two groups.
      Raloxifene treatment, on the other hand, did not cause proliferation. CONCLUSION:
      Estrogen alone or combined with progesterone may increase the risk of breast
      cancer by enhancing proliferation in the TDLU; raloxifen does not induce
      proliferation and may be a safe estrogen receptor modulator regarding its effects
      on mammary glands during menopause.

PMID- 16800254
TI  - Wire localisation biopsy of non-palpable breast lesions: reasons for unsuccessful
      excision.
AB  - Surgical excision following needle-wire localization of nonpalpable,
      mammographically detected breast lesions is a very valuable diagnostic and
      therapeutic procedure. No further treatment is usually required after
      establishing an accurate histological benign diagnosis of indeterminate lesions
      on preoperative assessment. On the other hand, ductal carcinoma in-situ (DCIS)
      and early invasive cancer, properly excised, may sometimes require further
      management depending on specific histologic findings. An uncommon problem of this
      procedure is the failure to identify, localize or excise the breast lesion. In
      this review article, factors that contribute to the failed needle localization
      procedure are presented.

PMID- 16800255
TI  - Cervical-vaginal disease in HIV immunosuppressed patients: management and present
      screening programme.
AB  - The aim of this study was to evaluate the rate of the cervical intraepithelial
      neoplasia (L-SIL and H-SIL) in HIV-positive patients using cytological,
      colposcopic and histological examinations. The correlations between these
      cervical lesions, the role of HPV and the clinical and immunological aspects of
      HIV infection and inflammatory cervical-vaginal disease were studied. We believe
      that HPV infection and preneoplastic and/or neoplastic lesions occur more often
      in immunodepressed HIV-positive patients, and that on the grounds of the high
      risk of precancerous lesions in this population and the low sensibility of the
      Pap test, it is advisable to perform a colposcopic examination to discover early
      lesions that must undergo a specific biopsy.

PMID- 16800256
TI  - Endometriosis and possible malignant transformation.
AB  - By examining the cause of infertility for a the period of three years in the two
      largest hospitals in Belgrade, we found 453 cases of endometriosis out of 683
      cases of laparoscopy. During the procedure, removal of endometrial foci,
      histological examination of the sample and removal of genital and peritoneum
      abnormalities by laser were carried out. Interestingly, in only 8% of the cases
      were cancerous changes of the ovary diagnosed. Out of 36 patients with
      established diagnoses, hysterectomy and bilateral salpingo-oophorectomy were
      performed in four cases.

PMID- 16800257
TI  - Uterine bizarre epithelioid lipoleiomyoma with a myxoid stroma.
AB  - The first case of uterine bizarre epithelioid lipoleiomyoma with a myxoid
      component occurring in an 86-year-old woman is described. An intramural 22 cm
      mass in the anterior wall of the uterine body had a lipoma-like appearance with
      strands of fibrous tissue. Histologically, the tumor consisted of adipocytes
      which varied in size and shape, and epithelioid smooth muscle cells with nuclear
      atypia within a myxoid stroma. No mitotic features were noted despite an
      extensive search. The patient was well without disease 24 months after
      hysterectomy. Patients with this type of tumor need close and long-term follow-up
      because of the paucity of clinical information.

PMID- 16800258
TI  - Surgical management of nipple discharge.
AB  - PURPOSE: Nipple discharge is reported in 2.5-3% of women with breast carcinoma.
      Breast carcinoma is found in approximately 8% of surgically treated patients
      presenting with bloody nipple discharge (ND). METHODS: In the present study 110
      women with ND as a presenting symptom were examined. The discharge was
      spontaneous in 76 and elicited in 11 patients. RESULTS: After surgical
      intervention benign breast disease was found in 85% of patients. Thirteen women
      (15%) were found to have malignancy and underwent additional surgery. Cytology of
      the discharge was positive or suspicious for malignancy in only seven out of 13
      patients found to have in situ or invasive carcinoma. CONCLUSION: Women with
      spontaneous, single duct ND, especially when it is darkish or bloody, should have
      cytological examination of the fluid and mammography according to their age or
      additional clinical findings. Most of them will require a microdochectomy, as the
      possibility of finding a carcinoma among those women is between 10-15%. However,
      single duct papilloma is the most common cause of bloody discharge.

PMID- 16800259
TI  - Amerindian women of the Brazilian Amazon and STD.
AB  - Papanicolaou tests, PCR for HPV, C. trachomatis, HSV-1/2 and N. gonorrhoea, and
      Hybrid Capture II were performed for high- and low-risk HPV groups during
      screening for cervical cancer in 49 women of the Parakana tribe. Cytological
      diagnoses of HPV were suggested in three samples: PCR showed 12 (22.4%) cases of
      DNA positive HPV, 16 (1), 18 (2), 58 (3), 39 (1), 61 (1), 33 (1), 35 (1), unknown
      (2), and HCII analyzed 48 samples: 19 positive (39.58%) for the high-risk group
      and four (18.33%) for the low-risk group. The prevalence of HPV was 42.85% (p =
      0.001) by molecular biology methods. The largest viral load was 1588.11 pg/ml for
      HPV 39 in a 16-year-old. PCR was positive for C. trachomatis and negative for HSV
      1/2 and N. gonorrhoea. Parakana women present a high risk for the development of
      cervical cancer.

PMID- 16800260
TI  - DCIS histopathology from a historical perspective.
AB  - Ductal carcinoma in situ (DCIS) represents a biologically and morphologically
      heterogeneous disease. It is characterized by a proliferation of presumably
      epithelial malignant cells confined within the lumens of the mammary ducts,
      without evidence of invasion beyond the basement membrane into the adjacent
      breast stroma. With the widespread use of screening mammography, a dramatic
      change has occurred in the frequency, management and types of DCIS detected.
      Historically, there has been some confusion regarding the definition of DCIS and
      the terminology associated with the histological types of DCIS. In this review,
      DCIS histopathology from a historical point of view is presented.

PMID- 16800261
TI  - Spontaneous transient rise of CD34 cells in peripheral blood after 72 hours in
      patients suffering from advanced malignancy with anemia: effect and prognostic
      implications of treatment with placental umbilical cord whole blood transfusion.
AB  - Cord blood, because of its rich mix of fetal and adult hemoglobin, platelet and
      WBC counts, and a plasma filled with cytokine and growth factors, as well as its
      hypoantigenic nature and altered metabolic profile, has all the potential of a
      real and safe alternative to adult blood during emergencies or any etiology of
      blood loss. STUDY DESIGN: In the present study transfusion-related CD34 levels of
      the peripheral blood from six randomly selected patients suffering from advanced
      clinical Stage IV malignancy were analyzed between 16 August 1999 and 16 May
      2001. This study attempts to ascertain the fate of hematopoietic stem cells
      (CD34) after placental umbilical cord whole blood transfusion, as assessed from
      the peripheral blood CD34 level 72 hours after cord blood transfusion in sex- and
      HLA-randomized patients. RESULTS AND ANALYSIS: Among the six cases, Case 2
      (breast sarcoma) received the lowest amount of card blood (6 units), while Case 6
      (breast cancer) received the largest amount (32 units). The youngest patient,
      suffering from non-Hodgkin's lymphoma (Case 3), was a 16-year-old boy who
      received eight units of cord blood to combat anemia. Other patients received
      amounts varying from 7-15 units: Case 4 received 15 units (metachronous lymph
      node metastatsis), Case 1 received 14 units (breast cancer), and Case 5 received
      seven units (lung cancer). There was no transfusion-related clinical
      immunological or nonimmunological reaction. Studies of CD34 levels showed an
      initial rise followed by a fall in two cases, two cases registered very little
      effect on the CD34 level, i.e., no change from the baseline, and one case
      demonstrated a very slow rise from the baseline. However, one case showed a
      frequent steep rise up to 99% and a sustained high CD34 level. This patient is
      alive with clinical remission of the disease. CONCLUSION: It appears from this
      preliminary study that freshly collected cord blood transfusion may cause a
      transient transplant impact of transfused cord blood CD34 stem cells on the host
      without provoking clinical graft vs host disease due to a of background immune
      suppression in advanced malignancy. The growth factor cytokine system of freshly
      collected cord blood may have a potentiating role on the immune system of the
      host.

PMID- 16800262
TI  - Third stage ovarian carcinoma--case report: the necessity of a multidisciplinary
      approach to treatment.
AB  - Ovarian carcinoma, part of a heterogeneous group of tumours, is the main cause of
      death by gynaecological neoplasms. The diagnosis, in general, is delayed.
      Multiorgan diffusion, the necessity of a surgical operation and strong
      chemotherapy, and the eventual pathology due to patient age are all factors that
      require a multidisciplinary approach. In fact the case, here reported, refers to
      a patient who came under our observation for a bilateral ovarian mass discovered
      casually during an abdominal ultrasound exam carried out for renal colic.
      Excellent cytoreduction with peritoneal cytology, total abdominal hysterectomy,
      bilateral salpingo-oophorectomy (Figure 2), bilateral pelvic lymphadenectomy,
      total omentectomy, removal of nodules from the mesentery, the colon and three
      nodules in the abdominal wall thickness was executed. The histological report was
      G3, angioinvasive bilateral ovarian endometrioid adenocarcinoma. Metastasis was
      found only in one left obturator lymph node out of 17 lymph nodes removed. All of
      the removed abdominal, mesenteric and intestinal nodules were neoplastic. It is
      concluded that the complexity of similar cases always requires a
      multidisciplinary approach as in our case, involving an oncologist, hematologist,
      surgeon, gynaecologist, radiologist, anaesthesiologist, and nursing staff in the
      management of third stage ovarian cancer patients to obtain the best treatment
      thus guaranteeing a higher survival rate and better quality of life.

PMID- 16800263
TI  - A giant uterine leiomyoma simulating an ovarian mass in a 16-year-old girl: a
      case report and review of the literature.
AB  - Uterine leiomyomas are extremely rare neoplasms in the pediatric and adolescent
      population. We report a case of a giant uterine leiomyoma measuring 30 cm in the
      largest diameter in a 16-year-old girl. To our knowledge this is the largest
      leiomyoma reported thus far in women under the age of 20 years. The patient was
      admitted to our hospital for the investigation of menstrual disorders, vaginal
      bleeding and progressive abdominal enlargement. Preoperative diagnosis was
      ovarian malignancy. Myomectomy was performed. Histopathologic study of the tumor
      showed an otherwise typical leiomyoma, both grossly and microscopically, with
      extensive hydropic and myxomatous degeneration and areas of prominent vessels,
      suggesting an angiomatous neoplasm. Leiomyomas in teenagers often exhibit
      histological features favoring the diagnosis of malignancy, and should be
      evaluated with extreme caution. The management of leiomyomas in these young
      patients should be conservative for the preservation of fertility.

PMID- 16800264
TI  - Recurrent endometrial stromal sarcoma after treatment with high-dose chemotherapy
      and autologous stem-cell support: A case report.
AB  - INTRODUCTION: The efficacy of high-dose chemotherapy plus transplantation of
      autologous hematopoetic stem cells in patients with endometrial stromal sarcomas
      is unknown. CASE REPORT: A 39-year-old woman with Stage III endometrial stromal
      sarcoma (ESS) underwent radical surgery, followed by five courses of ifosfamide,
      adriamycin and dacarbazine postoperatively. Six months after primary surgery stem
      cell priming was performed. Five months later bone marrow was aspirated and high
      dose chemotherapy with carboplatin, vepeside and holoxan were administered after
      which bone marrow was retransfused. Seven years after primary surgery the patient
      developed an abdominal recurrence which was removed surgically and adjuvant
      radiotherapy was administered. One year later the patient underwent hemicolectomy
      because of a new recurrence infiltrating the ascending colon. Treatment with 25
      mg exemestane was begun. The patient is currently alive and free of disease nine
      years after the initial diagnosis. CONCLUSION: Aggressive chemotherapy with
      autologous stem-cell support seems to be ineffective in patients with ESS.

PMID- 16800265
TI  - Metastases of the digestive tract and ovarian tumors--or vice versa: an analysis.
AB  - Ovarian carcinoma may appear regardless of age, including during childhood.
      Predisposing factors for the development of ovarian carcinoma are age (usually
      over 40), positive family history, mumps parotitis, small number of deliveries,
      environmental factors, persistant ovulation, etc. Metastases may appear in the
      ovary from almost all primary sites.

PMID- 16800266
TI  - Case study of a pregnant woman with decidualized ovarian endometriosis whose
      preoperative findings suggested malignant transformation.
AB  - BACKGROUND: Because both decidualization and malignant transformation of
      endometriosis are characterized by mural nodules on the wall of the cyst, the
      preoperative differential diagnosis is reportedly difficult. CASE: A 31-year-old
      woman was referred to our hospital at ten weeks of gestation. Sonographic
      examination revealed an intrauterine gestational sac and ovarian endometrial
      cyst. At 21 weeks of gestation, characteristic findings associated with malignant
      transformation of ovarian endometriosis were seen on color-flow Doppler
      sonography and contrast magnetic resonance imaging. Under the diagnosis of
      malignant transformation of ovarian endometriosis, right salpingo-oophorectomy
      was performed at 22 weeks' gestation. However, histopathologic examination
      revealed ovarian endometriosis with marked decidual changes but no evidence of
      malignancy. CONCLUSION: During pregnancy, intracystic vascularized excrescences
      of an endometrial cyst indicate not only malignant transformation but also
      decidualization. Thus, the preoperative differential diagnosis is reportedly
      difficult. However, the present findings of decidualization on magnetic resonance
      imaging seemed to be slightly different from those of malignant transformation,
      and therefore, might help distinguish decidualized endometriosis from malignant
      transformation preoperatively.

PMID- 16800267
TI  - Mucinous adenocarcinoma arising from the gastrointestinal epithelium in benign
      cystic teratoma of the ovary--case report.
AB  - Benign cystic teratoma of the ovary (BCTO) is the most common ovarian germ cell
      tumor occurring predominantly in early adulthood. Malignant transformation of a
      BCTO is rare, with an incidence of 2%. Most benign cystic teratomas with
      malignant transformations are squamous cell carcinomas with just 6.8% being
      adenocarcinomas. We present a rare case of adenocarcinoma arising from the
      gastrointestinal epithelial elements of BCTO based on the microscopic examination
      and immunohistochemical studies. Adenocarcinoma arising from gastrointestinal
      epithelium within BCTOs is extremely rare. This is the fifth reported case of
      adenocarcinoma arising in gastrointestinal epithelium of a BCTO.

PMID- 16800268
TI  - Double laparotomy wound recurrence of endometrial carcinoma.
AB  - INTRODUCTION: Abdominal scar recurrence of endometrial carcinoma after abdominal
      total hysterectomy is very rare. We report a case of a 65-year-old woman who had
      two recurrences in the abdominal incisional scar after total hysterectomy. CASE
      REPORT: A 65-year-old woman underwent total hysterectomy with bilateral salpingo
      oophorectomy and pelvic lymphadenectomy because of well-differentiated
      endometrial adenocarcinoma (Stage IIB). Thus, the patient was treated by external
      beam radiotherapy. She developed two recurrences in the abdominal incisional scar
      two and three years after total hysterectomy, respectively. Surgery plus
      chemotherapy and surgery plus hormonal therapy were used for treatment of the
      first and second scar recurrence, respectively. CONCLUSIONS: It is a very
      intriguing and controversial biologic question how neoplastic cells can implant
      and grow in an abdominal scar without other concomitant metastases. We report a
      review of the literature and the possible mechanism of recurrences in laparotomy
      wounds.

PMID- 16800269
TI  - Primary leiomyoma of the ovary in a young woman: literature review and report of
      a case.
AB  - Ovarian leiomyoma is a rare tumor. We present a case of ovarian leiomyoma in a 32
      year-old virgin with the complaint of dysmenorrhea for six months. On magnetic
      resonance imaging, a 6 cm x 4 cm mass in the left ovary exhibiting hypointense
      signals on both T1-weighted and T2-weighted images was initially considered to be
      fibroma and/or thecoma. However, after surgery the pathological diagnosis of the
      removed tumor was leiomyoma of the left ovary. The literature on this rare tumor
      was also reviewed.

PMID- 16800270
TI  - Female adnexal tumor of probable wolffian origin: clinicopathological,
      immunohistochemical and cytofluorimetric analyses of a 22-year-old virgin. case
      report.
AB  - The term female adnexal tumor of probable Wolffian origin "FATWO" designs this
      tumor wich arises by the rare persisting remnants of the mesonephric duct
      (Wolffian duct). About 40 cases have been reported in literature. Few cases of
      recurrence have been reported, FATWO usually shows no signs of hormonal activity.
      We report a case of the youngest patient affected by FATWO in October 2002. At
      laparotomy the left adnexa were deformed by a well-capsulated mass, totally
      removed and sent to the pathologist with a specimen of peritoneal fluid and of
      the omentum. The histological examination showed a prevalent tubular structure
      with focal retiform area, without intraluminal mucines. Immunohistochemical
      findings of the case reported are similar to those described by other authors,
      except for inhibin which has not been detected by us. The cytofluorimetry showed
      the low presence of aneuploid cells, with a very low prolifing component (< 1%).

PMID- 16800271
TI  - Sunscreen allergy: A review of epidemiology, clinical characteristics, and
      responsible allergens.
AB  - Although allergy to sunscreen represents a small proportion (< 1%) of allergic
      contact dermatitis reactions in North America, it is one of the most common
      causes of photoallergy. The epidemiology and clinical characteristics of
      sunscreen allergy are summarized in this review. In addition, a detailed
      discussion of specific chemical sunscreen allergens is provided.

PMID- 16800272
TI  - Should macular erythema reactions be counted as positive allergic patch-test
      reactions?
AB  - BACKGROUND: Positive allergic patch-test results are generally described as
      erythematous papules, vesicles, or a spreading reaction with crust and
      ulceration. This description excludes milder reactions, including macular
      erythema. OBJECTIVE: Our aim was to investigate the prevalence and relevance of
      reactions graded as macular erythema at Mayo Clinic. METHODS: Between January
      2001 and June 2004, patients suspected of having allergic contact dermatitis were
      patch-tested with our institution's standard patch test, a screening series of 68
      to 72 allergens. In total, 2,823 patients were patch-tested with 193,530 allergen
      applications. Reactions were interpreted with the North American Contact
      Dermatitis Group scale, including and excluding reactions graded as macular
      erythema. Irritant reactions were excluded from calculations. For this study,
      scores for current, questionable, and past relevance were combined. RESULTS: On
      day 5, with the exclusion of reactions graded as irritant, 7,274 allergen
      applications were associated with reactions, including 3,082 (42.4%) that were
      graded as macular erythema. Of the macular erythema reactions, 2,430 (78.8%) were
      graded as relevant. The rate of reaction in our patients was 2.2% if macular
      erythema was excluded, 3.8% if all macular erythema reactions were included, and
      3.4% if only those macular reactions deemed relevant were included. CONCLUSION:
      Patch-test reactions rated as macular erythema are common and may be of clinical
      relevance. For the purposes of patient education, they should not be disregarded.
      Consideration should be given to including these reactions when reporting
      patchtest results.

PMID- 16800273
TI  - Laser-assisted penetration of allergens for patch testing.
AB  - BACKGROUND: Patch-test patients often complain of itching and inconvenience.
      OBJECTIVE: To demonstrate (1) the usefulness of laser-assisted alteration of the
      stratum corneum to enhance allergen delivery and (2) patient satisfaction with
      this procedure. METHODS: The LAD-01 (erbium:yttrium-aluminum-garnet) laser unit
      was used to alter stratum corneum from patients with known sensitivity to nickel
      or Kathon CG. These allergens were then applied to the laser-pretreated sites for
      60 minutes. Results were observed at 24, 48, and 96 hours and at 1 week. One
      patient who refused conventional patch testing was tested with an entire modified
      North American standard series tray with the laser patch-test technique. An
      additional patient with previously demonstrated positive atopy patch-test
      reactions to environmental organisms was retested with laser pretreatment to the
      same antigens. RESULTS: Three of three patients known to be sensitive to Kathon
      CG and eight of eleven known nickel-sensitive patients had positive reactions at
      the laser-pretreated sites. The patient who was tested with the entire standard
      series demonstrated relevant positive reactions to formaldehyde and to a textile
      resin. One subject with known reactions to three environmental organisms
      reproduced patch-test responses with laser pretreatment. No irritant reactions
      were noted. Patients reported no pain. CONCLUSION: With further modification,
      laser pretreatment may improve patient convenience and decrease irritant test
      reactions owing to occlusion.

PMID- 16800274
TI  - Delayed-type hypersensitivity to fragrance materials in a select North American
      population.
AB  - BACKGROUND: In published reports from Europe, 3- and 4-(4-hydroxy-4
      methylpentyl)cyclohexene-1-carboxaldehyde (HMPCC) (Lyral) has been described as a
      common cause of allergic contact dermatitis (ACD). In Europe, the rates of
      reaction to HMPCC among patients undergoing patch testing for suspected ACD have
      varied from 1.2 to 17.0%, depending on the country. Data on the incidence of
      sensitivity to HMPCC among North Americans with suspected ACD have not been
      reported. OBJECTIVES: The goals of this study were (1) to assess the incidence of
      delayed-type hypersensitivity reactions to HMPCC among patients undergoing patch
      testing for evaluation of eczematous dermatitis at six centers throughout North
      America; (2) to determine the most appropriate concentration of HMPCC to use in
      performing patch tests; and (3) to compare and contrast the incidence rates for
      HMPCC hypersensitivity to those for other fragrance materials screened with the
      North American Contact Dermatitis Group (NACDG) screening tray, which includes
      fragrance mix, Myroxilon pereirae (balsam of Peru), cinnamic aldehyde, ylang
      ylang oil, jasmine absolute, and tea tree oil. METHODS: This report represents
      the prospective multicenter data on patients tested with the fragrance-related
      allergens on the NACDG standard screening tray and with HMPCC at 5%, 1.5%, and
      0.5% concentrations in petrolatum. Statistical analyses were performed with
      Student's t-test (two tailed) and the chi-square test. RESULTS: Data from 1,603
      patients evaluated at five US sites and one Canadian site were analyzed. Most
      patients (87.8%) were Caucasian. The majority (67%) were women, and 26.2% had a
      history consistent with atopic dermatitis. The patients ranged in age from 1 to
      88 years, and the mean +/- standard deviation was 46.3 +/- 16.5 years. Myroxilon
      pereirae (balsam of Peru) and fragrance mix were the most frequent patch-test
      positive fragrance allergens (6.6% and 5.9%, respectively). Cinnamic aldehyde
      (1.7%), ylang ylang oil (0.6%), jasmine absolute (0.4%), HMPCC (0.4% for 5%
      HMPCC, 0.3% for 1.5% HMPCC, and 0.2% for 0.5% HMPCC), and tea tree oil (0.3%)
      less frequently yielded positive reactions. Men were more likely than women to be
      allergic to cinnamic aldehyde. Women were more likely than men to be allergic to
      jasmine absolute. Atopic patients were no more likely to react to fragrance
      materials than were nonatopic patients. Patients who reacted to jasmine absolute
      tended to be older than the general population whereas those who reacted to tea
      tree oil tended to be younger than the general population. There were no other
      demographic differences between patients who reacted to a given fragrance
      material and the entire population studied. Testing with fragrance mix and balsam
      of Peru failed to identify the majority of patients in this study who were found
      to be sensitized to jasmine absolute, HMPCC, or tea tree oil. CONCLUSION: HMPCC
      is an uncommon allergen in the North American population. We recommend testing
      with 5% HMPCC in petrolatum for those patients suspected of having a fragrance
      allergy.

PMID- 16800275
TI  - Contact urticaria from carboxymethylcellulose in white chalk.
AB  - BACKGROUND: Carboxymethylcellulose (CMC) is widely used in consumer goods, foods,
      and medicaments as a binder, emulsifier, and viscosity enhancer. Cases of
      immediate and delayed allergic reactions to this anionic cellulose polymer have
      been reported. OBJECTIVE: To report a case of contact urticaria from CMC in
      chalk, with possible cross-reaction to methyl hydroxyethylcellulose (MHEC).
      METHOD: Patch tests with readings at 48 and 96 hours were performed with the
      North American Contact Dermatitis Group standard series and benzisothiazolinone.
      Open and prick tests with readings after 30 minutes were performed with two
      brands of chalk as well as with various petrolatum and aqueous dilutions of CMC,
      MHEC, oleic acid, and calcium carbonate. RESULTS: The patient developed strong
      urticarial reactions during open tests with both powdered chalks and had milder
      reactions to the open test with CMC 10% aqueous (aq) and to prick testing with
      CMC 0.1% aq. No reaction to MHEC or any of the other ingredients of the chalks
      was observed. No relevant delayed reaction was noted. CONCLUSION: CMC can cause
      contact urticaria. It remains unclear why our patient reacted more strongly to
      the chalk than to CMC itself. We speculate that the abrasive nature of the chalk
      enhances the cutaneous penetration of CMC or that calcium carbonate, the main
      ingredient of the chalk, acts as an adjuvant. It is also possible that CMC and
      MHEC cross-react and that our negative results with MHEC may be due to improper
      testing technique or concentrations.

PMID- 16800276
TI  - Pemphigus foliaceus with epidermal detachment: adverse events from patch testing.
AB  - Uncommon adverse reactions to patch testing have been reported, but few cases
      have shown patch testing to be a potential contraindication. We report a patient
      with known pemphigus foliaceus who had significant epidermal detachment of normal
      skin during the removal of patch-testing tape.

PMID- 16800277
TI  - Stevens-Johnson syndrome associated with glipizide therapy.
AB  - We describe a patient with Stevens-Johnson syndrome (erythema multiforme major)
      associated with an increase in glipizide dosage administration. Glipizide is a
      second-generation sulfonylurea commonly used to treat patients with noninsulin
      dependent diabetes mellitus. Although several reports have documented Stevens
      Johnson syndrome caused by first-generation sulfonylureas, our case appears to be
      the first report of a second-generation sulfonylurea associated with Stevens
      Johnson syndrome.

PMID- 16800278
TI  - The role of intradermal skin testing and patch testing in the diagnosis of
      autoimmune progesterone dermatitis.
AB  - Autoimmune progesterone dermatitis is a rare clinical condition in which patients
      display hypersensitivity to endogenous progesterone. It manifests as a cyclical
      cutaneous eruption that flares during the luteal phase of the menstrual cycle,
      when progesterone levels peak, and resolves partially or completely a few days
      after menses. Its cutaneous manifestations are variable and include urticaria,
      eczematous eruptions, vesiculopustular eruptions, fixed drug eruptions,
      stomatitis, erythema multiforme, and anaphylaxis. Autoimmune progesterone
      dermatitis has been diagnosed previously with intradermal skin testing or
      intramuscular progesterone challenge. Treatment of progesterone hypersensitivity
      generally consists of ovulation inhibition with pharmaceutical agents or
      oophorectomy; other therapies (eg, thalidomide) have also been used with success.
      We report a case of cyclical erythema multiforme (EM) induced by hypersensitivity
      to endogenous progesterone in a patient with a history of past oral contraceptive
      use. After herpes simplex virus was ruled out as an etiologic factor, a diagnosis
      of progesterone hypersensitivity was confirmed with intradermal skin testing.
      Results of subsequent patch testing with various progesterone derivatives were
      negative. The EM outbreaks were suppressed temporarily by continuous
      administration of Loestrin (ethinyl estradiol plus norethindrone), which also
      increased the responsiveness of the outbreaks to prednisone tapers.

PMID- 16800279
TI  - Periorbital dermatitis.

PMID- 16800280
TI  - Contact allergy presenting as erythroderma.

PMID- 16800281
TI  - The relationship of vehicle and concentration of imidazolidinylurea, with
      attention to formaldehyde allergy status.

PMID- 16800282
TI  - [Bone marrow cell as a source of hepatic stem cell].

PMID- 16800283
TI  - [Clinical significance of recurrence of hepatitis C virus after liver
      transplantation--Japanese experience--].

PMID- 16800284
TI  - [Prophylaxis and treatment for recurrent hepatitis C virus after liver
      transplantation].

PMID- 16800285
TI  - [Rumination syndrome in an adult with normal intelligence].
AB  - A 32-year-old woman visited our department because of repeated regurgitation of
      food, and was diagnosed with rumination syndrome based on possession of symptoms
      typical for it. Although rumination syndrome is classified as a functional
      esophageal disorder according to the Rome II criteria, it is not well known in
      Japan, and there have been no previous reports of it in an adult with normal
      intelligence. Since patients with rumination syndrome are often misdiagnosed and
      receive unnecessary treatment, awareness of it by physicians is important.

PMID- 16800286
TI  - [A case of primary duodenal cancer near the papilla of Vater which had initial
      symptoms of obstructive jaundice].
AB  - A 63-year-old man visited our hospital complaining of brown urine. A physical
      examination showed jaundice of the skin and conjunctiva bulbar. Blood tests
      showed elevated serum levels of bilirubin and hepatobiliary enzymes. A type 2
      like mass lesion was found near the papilla of Vater during the endoscopic
      retrograde cholangiopancreatography and was histologically proven to be a well
      differentiated adenocarcinoma. A diagnosis of obstructive jaundice due to primary
      duodenal cancer arising near the papilla of Vater was made. After the jaundice
      was decreased by endoscopic biliary stenting, a pancreatoduodenectomy was
      performed. A histopathological examination of the resected specimen concerning
      the location and manner of invasion of cancer cells revealed that the cancer
      arose from the duodenal mucosa near the papilla of Vater.

PMID- 16800287
TI  - [Bezafibrate alone is an effective first-line therapy for primary sclerosing
      cholangitis: a case report].
AB  - The patient was a 58-year-old female. Though she had been in good health,
      increased hepatobiliary enzymes were detected in a health examination. She
      visited our hospital for close examination. The serum IgG4 level was normal, but
      ERCP and MRCP showed band-like stricture and beaded appearance of the bile ducts.
      A diagnosis of primary sclerosing cholangitis (PSC) was made. Since
      hyperlipidemia was also observed, oral administration of bezafibrate (400mg/day)
      alone was performed as the initial treatment, and transaminase, ALP, and GGT
      rapidly decreased. These results suggested that the initial administration of
      bezafibrate alone is effective against PSC.

PMID- 16800288
TI  - [A case of polyarteritis nodosa with intra-abdominal bleeding due to rupture of
      the hepatic aneurysm].
AB  - A 39-year-old woman was admitted to our hospital because of abdominal pain. She
      was diagnosed as intra-abdominal bleeding and an emergency laparotomy was
      performed. On laparotomy, massive bleeding in the abdominal cavity due to a
      ruptured aneurysm of the intrahepatic artery was found. We also verified small
      aneurysm of the common hepatic artery, tinged with red, and was suspected
      systemic vasculitis. The post-operative course was uneventful, but the subsequent
      angiography revealed many other small aneurysm of hepatic, renal and lumbar
      aytery. Then it was diagnosed as polyarteritis nodosa. A case of polyarteritis
      nodosa presenting with intra-abdominal homorrhage like this case is rare, so we
      presented here together with a review of the literature.

PMID- 16800289
TI  - [A case of MALT lymphoma of the liver treated by RFA and Rituximab].
AB  - A 69 years old man was admitted to our hospital for further examinations of the
      liver tumor October, 2003. No underlying liver disease was found. Two tumors in
      the liver, 2cm in diameter respectively, were detected by abdominal
      ultrasonography and MRI scan. Ultrasonogram-guided needle biopsy from the liver
      tumor showed diffuse infiltration of CD20 positive, small lymphocytes. A distinct
      single band demonstrating clonal JH gene rearrangement was detected by southern
      blot analysis using tissues by needle biopsy. Thus, the patient was diagnosed
      with primary hepatic MALT lymphoma in the normal liver. These tumors were treated
      with percutaneus radiofrequency ablation (RFA), followed by Rituximab
      administration. No relapse has been noted until September, 2005.

PMID- 16800290
TI  - [A case of autoimmune pancreatitis complicated with immune thrombocytopenia].
AB  - A 80-year old man was referred to our hospital because of an elevation of serum
      amylase level. Diffuse enlargement of the pancreas was detected by abdominal
      computed tomography, and also diffuse narrowing of the main pancreatic duct was
      revealed using endoscopic retrograde cholangiopancreatography. The serum level of
      IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia
      developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet
      associated IgG, antiplatelet antibody and antinuclear antibody in serum were
      positive. The levels of serum complements were low. From all these findings the
      patient was diagnosed as autoimmune pancreatitis complicated with immune
      thrombocytopenia. The treatment with prednisolone was started, which was
      effective on each disease. The medication was suspended a year ago, and so far
      there is no data suggesting the recurrence of autoimmune pancreatitis or immune
      thrombocytopenia.

PMID- 16800291
TI  - Lymphangiogenesis and expression of specific molecules as lymphatic endothelial
      cell markers.
AB  - In recent years, several functional molecules specifically expressed and
      localized in lymphatic endothelial cells, such as 5'-nucleotidase, lymphatic
      vessel endothelial receptor-1, vascular endothelial growth factor receptor-3,
      podoplanin and Prox-1, have been identified. The discovery of the lymphatic
      endothelial cell markers facilitated detailed analysis of the nature and
      structural organization of the lymphatic vessels and their growth
      (lymphangiogenesis). As a result, over the past few years, advances have been
      made in understanding the cellular and molecular aspects of physiological
      lymphangiogenesis and tumor-induced lymphangiogenesis. The biology of
      lymphangiogenesis, particularly the mechanism of its regulation, is very
      important in understanding the formation of the lymphatic system as a biological
      regulation system transporting tissue fluid and wandering cells, including
      lymphocytes, and disease involving lymphangiogenesis. The understanding of the
      molecular mechanism of lymphangiogenesis and the elucidation of the development
      of normal and pathological tissues are expected to lead to the development of
      therapy for intractable diseases, such as malignant tumors and lymphedema.

PMID- 16800292
TI  - Formation and distribution of the sural nerve based on nerve fascicle and nerve
      fiber analyses.
AB  - The formation and distribution of the sural nerve are presented on the basis of
      an investigation of 31 legs of Japanese cadavers using nerve fascicle and fiber
      analyses. Nerve fibers constituting the medial sural cutaneous nerve were
      designated as 'T', whereas those constituting the peroneal communicating branch
      were designated as 'F'. In 74.2% of cases (23/31), the T and F fibers joined each
      other in the leg, whereas in 9.7% of cases (3/31) they descended separately. In
      16.1% of cases (5/31), the sural nerve was formed of only the T fibers. The sural
      nerve gave off lateral calcaneal branches and medial and lateral branches at the
      ankle. The lateral calcaneal branches always contained T fibers. The medial
      branches consisted of only T fibers, whereas most of the lateral branches
      consisted of only F fibers (71.0%; 22/31). In addition to the T and F fibers, P
      fibers, which derived from the superficial and deep peroneal nerves, formed the
      dorsal digital nerves. The P fibers were entirely supplied to the medial four and
      one-half toes. However, they were gradually replaced by the T and F fibers in the
      lateral direction. The 10th proper dorsal digital nerve consisted of T fibers
      only (38.7%; 12/31), of F fibers only (19.4%; 6/31) or of both T and F fibers
      (38.7%; 12/31). These findings suggest that the T fibers are essential nerve
      components for the skin and deep structures of the ankle and heel rather than the
      skin of the lateral side of the fifth toe. The designation of the medial sural
      cutaneous nerve should be avoided and only the T fibers are appropriate
      components for naming as the sural nerve.

PMID- 16800293
TI  - Projection field of primary afferent fibers innervating the ventral portion of
      the lumbar intervertebral disc in the spinal cord dorsal horn.
AB  - In the present study, we investigated the central projection of afferent fibers
      innervating the lumbar intervertebral disc using the fluorescent neurotracer 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). The tracer
      Dil was applied to the ventrolateral portion of the L5-L6 intervertebral disc in
      11 adult rats. Fluorescent sites were observed microscopically on spinal cord
      transverse sections. Fluorescent spots in laminae I-III were plotted on the
      central projection map of cutaneous afferents. In six of 11 rats, Dil was
      restricted to the application site. Of these six rats, three showed no evident
      fluorescent sites. In the remaining three rats, small fluorescent spots were
      scattered in the dorsal horn. Fluorescent spots in dorsal horn lamina I were
      located in the central projection fields of the low back and groin skin.
      Fluorescent spots were observed, also sporadically, in Clarke's column in T12-L1
      segments. The central projection of afferent fibers innervating the rat lumbar
      intervertebral disc was indistinct with Dil labeling. We presumed this was due to
      the scarcity of central terminal arbors of disc afferent fibers. Spotty
      projections in laminae I-IllIIere present near the central projection fields of
      the loin and groin, indicating that pain would be perceived in the groin.

PMID- 16800294
TI  - Anatomical study of the vertebral artery in Japanese adults.
AB  - The aim of the present study was to examine the vertebral arteries. The origins
      of the right and left vertebral arteries and their entrance points into the
      cervical transverse foramen were examined in dissections of 515 Japanese cadavers
      (303 males, 212 females) at Kurume University School of Medicine from 1990 to
      2003. There were 515 right vertebral arteries and 514 left vertebral arteries.
      The right vertebral artery originated from the right subclavian artery in 514 of
      515 arteries and one of the arteries arose from the bifurcation of the
      brachiocephalic trunk. The mean distance between the origin of the right
      subclavian artery and the right vertebral artery was 20.9 mm. The left vertebral
      artery originated from the left subclavian artery in 484 of 514 arteries and the
      mean distance between the origin of the left subclavian artery and the left
      vertebral artery was 32.1 mm. The remaining 30 arteries (5.8%) originated from
      the aortic arch between the left common carotid artery and the left subclavian
      artery and this frequency is similar to previously published data. There was no
      right-left difference for the entrance point of the vertebral arteries into the
      cervical transverse foramen and the 6th cervical vertebra (C6) was the most
      common entrance point. Seventy-eight percent of our cases had right and left
      vertebral arteries that originated in the subclavian arteries and entered the
      cervical transverse foramen at C6. Among the 30 left vertebral arteries that
      originated from the aortic arch, 20 arteries (66.7%) entered a cervical
      transverse foramen at a level higher than C6. This frequency was higher than that
      for the left vertebral artery that originated from the subclavian artery.

PMID- 16800295
TI  - Anatomical study of the human omohyoid muscle: regarding intermediate
      morphologies between normal and anomalous morphologies of the superior belly.
AB  - Intermediate morphologies between normal and anomalous morphologies of the
      superior belly of the omohyoid muscle (Om) were macroscopically and
      stereomicroscopically observed in 34 cadavers (24 males and 10 females aged
      between 51 and 97 years; average age 71.0 years) for anatomical practice, which
      had been preserved in the Department of Morphological Biology, Ohu University
      School of Dentistry. The intermediate morphologies were classified into four
      types on the basis of the developmental degree of the muscle fibers and the
      number and origin of the belly as follows: type 1, the anterior margin of the
      belly was unclear owing to poor myofiber development; type 2, the superior belly
      was composed of a posterior large belly and an anterior small belly; type 3,
      composed of three to five bellies, with the bellies arranged in a roof tile-like
      morphology; and type 4, the belly was composed of two bellies arranged anterior
      posteriorly parallel to each other (the anterior belly was found to be the
      inferior belly that had developed and reached the superior belly area). For the
      intermediate morphologies of the Om superior belly observed in the present study,
      although type 4 was due to the development of an inferior belly, the other three
      types were considered to be caused by the poor development of the myofibers in
      the formation process and by the division of the superior belly into two muscles,
      or secondary lamellar division of the belly with growth.

PMID- 16800296
TI  - Abnormal spermatogenesis in mice unable to synthesize ascorbic acid.
AB  - Although exposure to environmental toxicants, including endocrine-disrupting
      chemicals, is thought to be a possible cause of male infertility, the
      pathogenesis of male reproductive disorders remains unclear. In the present
      study, we used Gulo-/- mutant mice, which are unable to synthesize ascorbic acid,
      to study the importance of dietary vitamin C (VC) on spermatogenesis. Regular
      chow containing approximately 110 mg/kg VC is unable to support the growth of
      these mutant mice, but a VC supplement in their drinking water (330 mg/L) is able
      to ameliorate the VC deficiency. Testes of Gulo-/- mutants born from heterozygous
      mothers without VC supplement (VC-deficient mice) and those born from mothers
      given a VC supplement (VC-sufficient mice) were examined by morphological and
      biochemical analyses. Morphological analysis revealed that apoptosis of
      spermatocytes occurred frequently in VC-deficient mice at 20 days of age. Two
      dimensional electrophoresis analysis revealed the specific disappearance of heat
      shock protein (Hsp) 70 in the testes of 20-day-old VC-deficient mice. In the
      present study, the relationship between the apoptosis of spermatocytes and Hsp70
      in VC-deficient mice is discussed.

PMID- 16800297
TI  - Incidence of mylohyoid bridging in 13th century Byzantine mandibles.
AB  - Mylohyoid bridging on the mandible is a hyperostotic variation considered as one
      of the cranial non-metric characteristics. Most researchers have indicated that
      such non-quantitative traits can be used for the investigation of population
      history and these traits show differences according to societies. In the present
      study, we investigated the incidence of mylohyoid groove bridging on 89 half
      mandibles (48 right sides, 41 left sides; 39 complete mandibles, nine right and
      two left half-mandibles) from the Byzantine period, dated approximately eight
      centuries back. We observed that the incidence of mylohyoid bridging was 8.9% for
      the Byzantine mandibles with no side predilection. The incidence of bridging
      observed in the present sample was compared with those of earlier studies.
      Mylohyoid bridging may be useful as a non-metric feature in population studies
      when used in combination with other characteristics.

PMID- 16800298
TI  - Double innervation of the anterior belly of the digastric muscle.
AB  - We came across a very rare case in which the anterior belly of the digastric
      muscle was innervated by the twigs of the facial nerve in addition to those of
      the mylohyoid nerve. The anomaly was discovered in the cadaver of an 84-year-old
      Japanese male bequeathed for a training seminar in gross anatomy at Kumamoto
      University in 2003. One twig issued from the marginal mandibular branch of the
      facial nerve and entered the central region of the anterior belly of the
      digastric muscle on the lower surface. The other twig issued from the stylohyoid
      branch of the facial nerve, descended along the lateral margin of the stylohyoid
      muscle and entered the anterior belly of the digastric muscle on the lower
      surface near the intermediate tendon. The twig from the marginal mandibular
      branch was distributed to the shallow (lower) and central region near the medial
      margin of the anterior belly. The twig from the stylohyoid branch was distributed
      to the shallow and lateral region of the anterior belly. These two twigs
      communicated with the mylohyoid nerve at several peripheral parts. Textbooks on
      general anatomy make mention of only one nerve, the mylohyoid, supplying the
      anterior belly of the digastric muscle. However, the present case manifests that
      the anterior belly receiving twigs from the mylohyoid and facial nerves is formed
      with the second brachial component as well as the first.

PMID- 16800299
TI  - An ultrastructural study of development and reproduction in the nematode parasite
      Myzocytiopsis vermicola.
AB  - An isolate of Myzocytiopsis vermicola, a holocarpic parasite of Rhabditis
      nematodes, was studied with transmission electron microscopy (TEM) to follow
      development during infection, asexual and sexual reproduction. Nematodes became
      infected after attachment of apical cystospore buds to the nematode cuticle.
      Apical buds were packed with vesicles with dense fibrillar contents, which were
      absent from the thallus. Some thalli developed into sporangia while others became
      paired gametangial cells. Zoospore cleavage was often intrasporangial, although
      during the early stages of an epidemic partially differentiated zoospores usually
      were released via an exit tube into a fine vesicle. Packets of tripartite tubular
      hairs (TTH) were not observed in the cytoplasm of either developing or mature
      sporangia. TEM of sectioned material and whole mounts of zoospores revealed
      biflagellate zoospores, some without hairs and others with a proximal row of very
      short hairs on the anterior flagellum. Gametangial contact was via a short,
      walled fertilization tube and surplus antheridial and oogonial nuclei remained in
      their respective gametangial cells until disintegration of the periplasm. The
      mature oospores had a scalloped, electron opaque, epispore wall layer. These
      observations will be discussed in relation to the likely phylogenetic position of
      the Myzocytiopsidales within the oomycetes.

PMID- 16800300
TI  - Fungal spore diversity of arbuscular mycorrhizal fungi associated with spring
      wheat: effects of tillage.
AB  - We investigated the influence of tilling, N fertilization and crop stage on
      arbuscular mycorrhizae (AM) fungal species diversity in a wheat monoculture in
      the Pampa region of Argentina. Glomalean spores were isolated by wet sieving and
      decanting from conventionally tilled and nontilled soils cropped with wheat with
      or without N fertilization, at three phenological stages of the crop (tilling,
      flowering and grain filling) and fallow. Morphological characterization yielded
      at least 24 AM fungi taxa in the field samples, belonging to six genera of AMF:
      Acaulospora Archaeospora, Entrophospora, Gigaspora, Glomus and Scutellospora.
      Tilling and fertilization treatments did not result in decreased spore
      biodiversity. Wheat phenology influenced AM communities, with highest spore
      biodiversity during grain filling.

PMID- 16800301
TI  - Characterization and identification of field ectomycorrhizae of Boletus edulis
      and Cistus ladanifer.
AB  - Field ectomycorrhizae sampled under Boletus edulis and Cistus ladanifer have been
      characterized and described in detail based on standard morphological and
      anatomical characters. The described ectomycorrhiza has traits typical of
      Boletales: whitish with three differentiated plectenchymatous layers in the
      mantle in plan view forming ring-like structures and rhizomorphs with highly
      differentiated hyphae. The inflated, smooth cystidia-like clavate end cells on
      the surface of the rhizomorphs and their slightly twisted external hyphae are
      additional characterizing features. The Hartig net occupies 1 1/2 rows of
      cortical cells, partly reaching the endodermis. Not all hyphae have clamps. The
      identification of the fungal symbiont as B. edulis was confirmed by ITS rDNA
      sequence comparison between mycorrhizas and sporocarps. The singularity of this
      symbiotic association, as well as its ecological and practical implications, are
      discussed.

PMID- 16800302
TI  - Penicillium species endophytic in coffee plants and ochratoxin A production.
AB  - Tissues from Coffea arabica, C. congensis, C. dewevrei and C. liberica collected
      in Colombia, Hawaii and at a local plant nursery in Maryland were sampled for the
      presence of fungal endophytes. Surface sterilized tissues including roots,
      leaves, stems and various berry parts were plated on yeast-malt agar. DNA was
      extracted from a set of isolates visually recognized as Penicillium, and the
      internal transcribed spacer region and partial LSU-rDNA was amplified and
      sequenced. Comparison of DNA sequences with GenBank and unpublished sequences
      revealed the presence of 11 known Penicillium species: P. brevicompactum, P.
      brocae, P. cecidicola, P. citrinum, P. coffeae, P. crustosum, P. janthinellum, P.
      olsonii, P. oxalicum, P. sclerotiorum and P. steckii as well as two possibly
      undescribed species near P. diversum and P. roseopurpureum. Ochratoxin A was
      produced by only four isolates, one isolate each of P. brevicompactum, P.
      crustosum, P. olsonii and P. oxalicum. The role these endophytes play in the
      biology of the coffee plant remains enigmatic.

PMID- 16800303
TI  - Heterokaryon incompatibility function of barrage-associated vegetative
      incompatibility genes (vic) in Cryphonectria parasitica.
AB  - Six vegetative incompatibility (vic) loci have been identified in Cryphonectria
      parasitica based on barrage formation during mycelial interactions. We used
      hygromycin B- and benomyl-resistance as forcing markers in C. parasitica strains
      to test whether heteroallelism at each vic locus prevents heterokaryon formation
      following mycelial interactions. Paired strains that had allelic differences at
      any of vic1, 2, 3, 6 or 7 but not vic4 displayed heterokaryon incompatibility
      function, as recognized by slow growth or aberrant morphology. While clearly
      forming barrages in mycelial interactions, paired strains with different alleles
      at vic4 formed stable heterokaryons. With examples from other fungi, this
      inconsistency at vic4 suggests that barrage formation and heterokaryon
      incompatibility are not different manifestations of the same process. Rather, the
      evidence indicates that heterokaryon incompatibility represents a component of a
      vegetative incompatibility system that may also use cell-surface or extracellular
      factors to trigger programmed cell death to modulate nonself recognition in
      fungi.

PMID- 16800304
TI  - Mitochondrial inheritance patterns in Didymium iridis are not influenced by stage
      of mating competency.
AB  - To test whether the timing of transition to mating competency affected
      mitochondrial transmission patterns in D. iridis. Reciprocal crosses were made by
      combining mating compatible strains that differed in their competency to mate.
      The results were compared to crosses where both mating strains were competent at
      the time of combining and crosses where somatic fusion of plasmodia was allowed.
      The results show that the mating competency of the parental strains at the time
      of confronting a compatible mate does not affect mitochondrial transmission
      patterns, mating efficiency or the likelihood of biparental inheritance. However
      the timing of plasmodial formation is delayed when precompetent and competent
      strains are mated compared to when both strains are competent at the time of
      mixing. We also observed that somatic fusion of plasmodia did not appreciably
      increase the incidence of biparental inheritance compared to crosses where
      individual plasmodia were isolated. These results provide additional evidence of
      the variable nature of mitochondrial inheritance in D. iridis within crosses and
      between mating trials.

PMID- 16800305
TI  - A study of the genetic variability of Rhizoplaca chrysoleuca using DNA sequences
      and secondary metabolic substances.
AB  - Specimens of Rhizoplaca chrysoleuca from Mount Wuling can be divided into two
      distinct groups based on obvious differences in morphological characters. Here we
      investigated 26 specimens of R. chrysoleuca from Mount Wuling, 10 specimens of
      this species from other areas and seven specimens of other Rhizoplaca species by
      analyzing morphology, chemistry and genetics. Nine chemotypes were detected among
      the specimens of R. chrysoleuca from Mount Wuling, and five of them were reported
      for the first time. Based on the ITS phylogenetic analysis, the chemotypes and
      the insertion distribution patterns in SSU rDNA, the samples of R. chrysoleuca
      from Mount Wuling were grouped in two distinct clades corresponding to two
      phenotypic groups and no gene flow was detected between these two groups. Our
      results establish all individuals of Rhizoplaca chrysoleuca are conspecific
      although some populations have been isolated on Mount Wuling, indicating that
      they are in the process of speciation. Our study also reveals that the
      relationships between genotypes and chemotypes are complicated and should be
      avoided, and we instead recommend using single individuals or few individuals
      from the same site to represent the population or whole species in systematics
      study. The results also indicate that Rhizoplaca chrysoleuca might provide a good
      model for studying the speciation of saxicolous lichenized fungi.

PMID- 16800306
TI  - Molecular systematics of Ceratostomella sensu lato and morphologically similar
      fungi.
AB  - The systematic position and phylogenetic relationships of Ceratostomella sensu
      lato and phenotypically similar fungi using comparative morphological and culture
      studies and phylogenetic analyses of the nuclear large- and small-subunit
      ribosomal DNA were explored. In the light of inferred phylogenies and
      morphological data the genus Ceratostomella is redescribed, the generic concept
      is emended and four species are accepted (viz. C. cuspidata, C. pyrenaica, C.
      rhynchophora and C. rostrata). A new genus Xylomelasma is introduced and
      delimited from Ceratostomella, with two new species described (viz. X.
      novaezelandiae and X. sordida). In culture species of both Ceratostomella and
      Xylomelasma produced sterile mycelium. The genus Lentomitella with a phaeoisaria
      like anamorph formed in vitro is reinstated to encompass taxa formerly attributed
      to the broadly perceived Ceratostomella with three accepted species (viz. L.
      cirrhosa, L. crinigera and L. tomentosa). Lentomitella and Ceratostomella are
      clearly distinguishable by the morphology of asci, ascospores and centrum.
      Lentomitella is compared to phenotypically similar Ceratosphaeria, which formed a
      harpophora-like anamorph in vitro. In the present phylogenies Ceratostomella,
      Ceratosphaeria, Lentomitella and Xylomelasma are shown as clearly separate genera
      belonging to three different groups of perithecial ascomycetes. Ceratostomella,
      Lentomitella and Xylomelasma reside within a large unsupported clade consisting
      of members the Ophiostomatales, the freshwater Annulatascaceae and a group of
      nonstromatic, terrestrial taxa. Ceratosphaeria is well supported within the
      Magnaporthaceae. The systematic value of morphological characters of ascospores,
      paraphyses, asci, centrum and conidiogenesis in segregating taxa from
      Ceratostomella sensu lato and their relatives is discussed.

PMID- 16800307
TI  - Molecular systematics of Helicoma, Helicomyces and Helicosporium and their
      teleomorphs inferred from rDNA sequences.
AB  - Three genera of asexual, helical-spored fungi, Helicoma, Helicomyces and
      Helicosporium traditionally have been differentiated by the morphology of their
      conidia and conidiophores. In this paper we assessed their phylogenetic
      relationships from ribosomal sequences from ITS, 5.8S and partial LSU regions
      using maximum parsimony, maximum likelihood and Bayesian analysis. Forty-five
      isolates from the three genera were closely related and were within the
      teleomorphic genus Tubeufia sensu Barr (Tubeufiaceae, Ascomycota). Most of the
      species could be placed in one of the seven clades that each received 78% or
      greater bootstrap support. However none of the anamorphic genera were
      monophyletic and all but one of the clades contained species from more than one
      genus. The 15 isolates of Helicoma were scattered through the phylogeny and
      appeared in five of the clades. None of the four sections within the genus were
      monophyletic, although species from Helicoma sect. helicoma were concentrated in
      Clade A. The Helicosporium species also appeared in five clades. The four
      Helicomyces species were distributed among three clades. Most of the clades
      supported by sequence data lacked unifying morphological characters. Traditional
      characters such as the thickness of the conidial filament and whether
      conidiophores were conspicuous or reduced proved to be poor predictors of
      phylogenetic relationships. However some combinations of characters including
      conidium colour and the presence of lateral, tooth-like conidiogenous cells did
      appear to be predictive of genetic relationships.

PMID- 16800308
TI  - Aurapex penicillata gen. sp. nov. from native Miconia theaezans and Tibouchina
      spp. in Colombia.
AB  - Conidiomata of a fungus resembling Chrysoporthe cubensis, a serious canker
      pathogen of Eucalyptus spp. (Myrtaceae, Myrtales) in tropical and subtropical
      parts of the world, was found on Eucalyptus grandis in Colombia. Fruiting
      structures of the fungus could be distinguished from those of C. cubensis by
      their distinctly orange conidiomatal necks. This fungus also was found on several
      plant species native to Colombia including Tibouchina urvilleana, T. lepidota and
      Miconia theaezans (Melastomataceae, Myrtales). Morphological comparisons, as well
      as those based on sequences of the ITS1/ITS2 region of the ribosomal DNA repeat
      and the beta-tubulin gene, were used to characterize this fungus. Its
      pathogenicity was assessed on various plants from which it has been collected,
      either in field or greenhouse trials. Phylogenetic analyses showed that isolates
      reside in a clade distinct from the four clades accommodating Chrysoporthe,
      Cryphonectria, Endothia and Rostraureum. Members of this clade are distinguished
      by the presence of orange conidiomatal necks with black bases and a unique
      internal stromatal structure. No teleomorph has been found for this fungus, for
      which we have provided the name Aurapex penicillata gen. sp. nov. A. penicillata
      produced only small lesions after inoculation on young T. urvilleana, M.
      theaezans and E. grandis trees and appears not to be a serious pathogen.

PMID- 16800309
TI  - Pythiogeton zizaniae, a new species causing basal stalk rot of water bamboo in
      Taiwan.
AB  - A new species, Pythiogeton zizaniae, was isolated from diseased water bamboo
      (Zizania latifolia) in central Taiwan. The organism formed a colony with scanty
      mycelia and mycelial aggregates on rye-water bamboo medium. Special treatments
      were required for production of sporangia which were terminal, noncaducous and
      mostly ovoid. Chlamydospores were absent. The fungus was homothallic. Oogonia
      produced on V-8 water bamboo medium in water were mostly globose to subglobose
      and each was attached with a club-shaped, monoclinous antheridium by the base of
      the oogonium stalk. Oospores were plerotic and globose to subglobose. Py.
      zizaniae caused death of water bamboo suckers but did not infect seedlings of
      corn, rice, wheat, sorghum, cucumber, tomato, soybean or water spinach. It also
      did not affect cucumber and tomato fruit, carrot roots or potato tubers.

PMID- 16800310
TI  - Systematics of the genus Chaetosphaeria and its allied genera: morphological and
      phylogenetic diversity in north temperate and neotropical taxa.
AB  - Chaetosphaeria is a common saprobic pyrenomycete genus with simple, homogeneous
      teleomorphs and complex, diverse anamorphs. As currently circumscribed in the
      literature, the genus encompasses 30 species distributed in four 'natural
      groups', and includes morphological entities in 11 anamorphic genera. Species
      frequently have been defined primarily based on characters of the anamorphs
      resulting in species with almost indistinguishable teleomorphs. This study aimed
      to assess the value and significance of morphological characters in resolving
      phylogenetic relationships in Chaetosphaeria and its allied genera. Phylogenetic
      relationships of 42 taxa, representing 29 species distributed in Chaetosphaeria
      and five related genera, were estimated with partial sequences of the nuclear LSU
      rDNA and beta-tubulin genes. Sequences were analyzed with maximum parsimony,
      maximum likelihood and Bayesian methods. Phylogenetic analyses of these two genes
      combined revealed two major lineages. The Chaetosphaeria lineage includes 21
      species possessing both typical and new sexual and asexual morphologies. The
      lineage contains a strongly supported monophyletic clade of 13 species and eight
      paraphyletic taxa; the latter includes C. innumera, the type species of the
      genus. The second major lineage includes groupings concordant with the
      morphological circumscriptions of the genera Melanochaeta, Melanopsammella,
      Striatosphaeria, Zignoella and the new genus Tainosphaeria.

PMID- 16800311
TI  - Crepidotus rubrovinosus sp. nov. and Crepidotus septicoides, found in the cloud
      forest of eastern Mexico, with notes on Crepidotus fusisporus var. longicystis.
AB  - Two species of Crepidotus are recorded from cloud forest in the central region of
      Veracruz State (eastern Mexico): Crepidotus rubrovinosus sp. nov. and Crepidotus
      septicoides. The latter species was known previously only from the type locality
      in Brazil and from one record in tropical rain forest in southern Veracruz (as C.
      longicystis s. str. Singer). Descriptions, illustrations and discussions for both
      taxa are provided. A type study of C. fusisporus var. longicystis from USA is
      included, and it is concluded that the collection supporting this variety belongs
      to C. luteolus.

PMID- 16800312
TI  - A new name for Torula glutinosa in Heteroconium.
AB  - Torula glutinosa, a sooty mold on living leaves and stems of Eriodictyon spp.
      from California is illustrated and described. It shares, with the type species of
      Heteroconium, H. citharexyli, acropetal conidiogenesis of chains of conidia of
      variable length and acropetal transseptation. An unnamed synanamorph is
      recognized and described.

PMID- 16800313
TI  - A new ballistosporous species of Protostelium.
AB  - During surveys of the protostelids of the Hawaiian Islands and the South Island
      of New Zealand, an undescribed species of Protostelium was discovered fruiting on
      collections of substrates found in several sites on the southern and western
      parts of the island of Hawaii and from one site near Port Elizabeth, New Zealand.
      The new species, P. okumukumu, has a sporocarp with a bipartite stalk that
      supports a single, spherical spore. The basal portion of the stalk is straight
      and rigid. The upper part of the stalk is a nearly spherical apophysis. The
      junction between the stalk base and the apophysis is flexible such that the spore
      and apophysis swing back and forth as a unit. Spores are forcibly discharged from
      the stalk, and only the straight base of the stalk is left behind. Amoebae
      typical of the taxon Protostelium germinate from the spores, and when an amoeba
      differentiates into a prespore cell, it becomes lozenge shaped (nearly ellipsoid)
      in top view, as is typical for species of Protostelium. This represents the
      seventh species of protostelids described to have forcible spore discharge, and
      the possibility of forcible discharge needs to be examined in several other
      species.

PMID- 16800314
TI  - A new Leptographium species associated with the northern spruce engraver, Ips
      perturbatus, in western Canada.
AB  - An undescribed Leptographium species was isolated from the spruce-infesting bark
      beetle Ips perturbatus collected from felled spruce trees and logs in northern
      British Columbia and Yukon Territory. Morphologically, this fungus is similar to
      L. abietinum and L. hughesii but differed in a number of characteristics (e.g.
      the arrangement of its conidiophores). The fungus grew optimally at 25 C on 2%
      malt-extract agar and showed a high level of tolerance to cycloheximide.
      Comparison of rDNA and beta-tubulin gene sequences also confirmed that this
      Leptographium species represents an undescribed taxon. Thus we described it as a
      new species, Leptographium fruticetum sp. nov.

PMID- 16800315
TI  - Do you have the time--or the money--to offer HIV screenings?
AB  - If you want to have a successful HIV testing program, make sure you have
      sufficient financing in place, sufficient time to handle the additional testing,
      and adequate counseling staff available. New guidelines from the Centers for
      Disease Control and Prevention encourage all EDs to offer HIV testing. Plan on
      annual costs of dollar 300,000- dollar 400,000. If your hospital won't provide
      the funds, government grants are an excellent source. If you can't hire
      counselors, form a partnership with your public health department. New rapid
      testing can cut down on time constraints; be aware, however, that they are not
      100% accurate.

PMID- 16800316
TI  - CDC to change HIV test guidelines.

PMID- 16800317
TI  - Fingerprint scanners help improve record security.
AB  - Technological solutions such as fingerprint scanners and identification badges
      provide greater computer security and piece of mind for your staff, according to
      ED managers at St. John's Mercy Medical Center in Chesterfield, MO. 'Proximity
      badge' is the computer log in, and staff member's fingerprint is their password.
      Busy physicians and nurses can leave the department to see patients in waiting
      areas without worrying about someone accessing their computer. Staff has noted
      some system glitches, including the need to place fingers in the scanner several
      times.

PMID- 16800318
TI  - ED diversions banned by Seattle-area hospitals.
AB  - With the proper system, EDs truly can avoid diversions without becoming too
      overloaded to handle critically ill patients. A "fail-safe" process that allows
      EDs to go on saturation for two hours acts as a safety valve to ensure flow. When
      all EDs in the area agree to the same procedures, it avoids any single ED
      becoming overwhelmed by an influx of patients. Working in cooperation with other
      EDs gives your argument greater weight when asking administrators to take a
      hospitalwide approach to flow improvement.

PMID- 16800319
TI  - ED located next to ICU to bolster patient safety.
AB  - Thinking ahead in the design process can help eliminate potential barriers to
      optimal patient safety: Eliminating the need to transport patients to distant
      departments lessens the risk of harm--for example, IV tubes being dislodged in
      transit. Nurses don't really have to "leave" their patients to help out in
      adjacent units. Standardization of room equipment placement makes it easier for
      nurses from one department to work in another.

PMID- 16800320
TI  - Patient flow initiatives slash average LOS.
AB  - By combining several patient flow initiatives at once, you can generate better
      results, as each improvement complements the others: A rapid admit unit allows
      your staff to see a greater number of patients. Bed tracking system complements
      rapid admit unit by showing availabilities and balancing bed usage in the units.
      Bedside admission helps increase the speed at which a bed assignment can be made.

PMID- 16800321
TI  - In-house 'access center' relieves ED bed burden.
AB  - A separate "Access Center," with its own staff, can handle several tasks that
      might otherwise be done by ED staff, thereby freeing more of their time to treat
      patients. Direct admits are handled by the center immediately, so those patients
      never are seen by the ED. ED staff phone calls to primary care physicians to
      discuss unscheduled admissions are totally eliminated. ED manager says a
      significant amount of pressure is taken off her supervisors.

PMID- 16800322
TI  - SUNA: meeting the kaleidoscope of care.

PMID- 16800323
TI  - Recreating your job.

PMID- 16800324
TI  - Genital piercings: what is known and what people with genital piercings tell us.
AB  - General and subjective information about those who chose to obtain genital
      piercings was presented. Particularly, the assumptions made from the literature
      are refuted by objective and subjective data collected from intimately pierced
      individuals themselves. Professional nurses must not base practice decisions on
      assumptions but on the "best evidence with clinical experience, research, (as
      well as) associated patient values" (Sackett, Strauss, Richardson, Rosenberg, &
      Haynes, 2001, p. 10). Thus, providing clinically competent care is driven by the
      latest knowledge and evidence from research and patient sources. Data found here
      provide further empirical evidence that may help to improve client outcomes by
      advancing evidence-based nursing practice in relation to people with genital
      piercings.

PMID- 16800325
TI  - To circ or not to circ: indications, risks, and alternatives to circumcision in
      the pediatric population with phimosis.
AB  - Summary Although there continues to be considerable debate over the merits of
      circumcision, it is clear that preservation of the pediatric foreskin, even in
      the presence of phimosis, is a viable option. Steroid topical cream is a
      painless, less-complicated, and more economical alternative to circumcision for
      treating phimosis. Success rates are quite high, especially when patient
      selection is appropriate and parents are adequately instructed on application. In
      those children in whom topical steroid therapy has failed, there remains a
      variety of foreskin-preserving surgical options for treating phimosis. Compared
      to circumcision, these less-invasive techniques are associated with lower
      morbidities and cost. Furthermore, depending on the tissue-preserving technique
      used, satisfactory cosmesis is also achieved. Thus, those males who were not
      circumcised at birth now have medical and surgical options, which will decrease
      the likelihood of requiring circumcision at an older age. As health care
      providers in the United States see more and more uncircumcised male children, it
      is important for these children and their parents to understand the natural
      history of physiologic phimosis. Additionally, it is the responsibility of health
      care providers to present the management options available for the treatment of
      the persistent nonretractile foreskin and/or pathologic phimosis. These options
      are particularly important for those individuals whose religious, cultural, or
      personal preference is to retain the foreskin.

PMID- 16800326
TI  - Urinary tract infections: role of the clinical microbiology laboratory.

PMID- 16800327
TI  - Hormone ablation for the treatment of prostate cancer: the lived experience.

PMID- 16800328
TI  - Getting ready for certification: urinary tract inflammations and infections.

PMID- 16800329
TI  - The challenge of treating enuresis.

PMID- 16800330
TI  - Suprapubic catheter replacement.

PMID- 16800331
TI  - Cholesterol, cholesterol lowering agents/statins, and urologic disease: part II-
      do you know your Framingham Risk Score?

PMID- 16800332
TI  - Pay for performance: quality and cost control go arm in arm.
AB  - Is pay for performance (P4P) motivated by cost savings or the quest for quality
      care? The answer depends on whose P4P program is being discussed.

PMID- 16800334
TI  - Keeping the contract. An interview with the new AHA Chair-Elect Kevin Lofton.
      Interview by Mary Grayson.
AB  - The AHA's chair-elect talks with Health Forum Publisher and Editorial Director
      Mary Grayson about alliances, diversity, transparency and the need to renew
      health care's social contract.

PMID- 16800333
TI  - Putting change on the fast track. Could accelerated decision making help your
      board?
AB  - Following the example of West Coast high-tech companies, one Midwest health care
      system is using a process called Accelerated Decision Making to sharpen and speed
      up its approach to long- and short-term strategic planning.

PMID- 16800335
TI  - Governance challenges in the year ahead.

PMID- 16800336
TI  - Mike Kelly: renaissance man.

PMID- 16800337
TI  - Gaps in the HIPAA Chinese wall.

PMID- 16800338
TI  - Managing CEO transition.

PMID- 16800339
TI  - The audit committee and Sarbanes-Oxley.

PMID- 16800340
TI  - Avian influenza: waiting for Godot?

PMID- 16800341
TI  - Effects of tamoxifen therapy on plasma lipid profile in patients of breast
      cancer.
AB  - AIM: To evaluate the effects of tamoxifen therapy on plasma lipid profile in
      patients of breast cancer. METHOD: A total of 55 postoperative patients of breast
      cancer were given tablet tamoxifen 20mg orally daily for 6 months. Estimation of
      plasma lipid by standard method was carried out in both pre-menopausal and
      postmenopausal new patients of early stage breast cancer at 0 day, 3rd month and
      6th months of therapy. RESULTS: Suggested that in pre-menopausal and
      postmenopausal patient's TC and LDL-c levels were reduced significantly, whereas,
      TG, VLDL-c and HDL-c were not altered. Comparison of the effects of tamoxifen in
      pre-menopausal and postmenopausal patients on lipid profile revealed that fall in
      TC and LDL-c was significantly higher at both 3 and 6 months in postmenopausal
      patients. CONCLUSION: The study demonstrates that tamoxifen to favorably alter
      the markers of cardiovascular risk in both pre-menopausal and postmenopausal
      patients of breast cancer.

PMID- 16800342
TI  - Spectrum of clinico-pathological changes in Barrett oesophagus.
AB  - OBJECTIVES: Barrett oesophagus is replacement of squamous epithelium to
      specialised intestinal metaplasia. It is associated with an increased risk for
      adenocarcinoma which develops through dysplasia. The aim of this retrospective
      study was to determine the relative age of occurrence and incidence of dysplasia
      in this part of our country. METHODS: Between January 1999 and June 2002 we
      diagnosed 13 cases of Barrett oesophagus. Sections were stained with routine H
      and E and special stain alcian blue (AB)--PAS at pH 2.5. RESULTS: Out of 55
      patients with symptoms of gastro-oesophageal reflux disease, 13 cases were
      diagnosed as Barrett oesophagus. There were 8 males and 5 females. Majority of
      the patients (77%) were between 20-40 years of age. At endoscopy, in 84.6%
      patients, lesions were in the form of islands of red mucosa. On histology
      examination, in 6 cases, squamous epithelium was replaced by intestinal
      epithelium containing goblet cells and in 7 cases it was replaced by gastric
      epithelium. Associated dysplasia was not seen in any of the case, while one case
      showed associated adenocarcinoma. CONCLUSION: Barrett oesophagus is seen in a
      younger population amongst Indians. A male predominance is noted, but is not as
      high as reported in Western literature. There is a paucity of patients with pure
      dysplasia in Barrett metaplasia. Despite the fact that there are a number of
      patients presenting with Barrett esophagus and carcinoma, very few patients
      present with dysplasia, indicating that Barrett oesophagus is a silent disease
      presenting later as a carcinoma.

PMID- 16800343
TI  - Micronuclei evaluation of reduction in neoadjuvant chemotherapy related acute
      toxicity in locally advanced lung cancer: an indian experience.
AB  - BACKGROUND: Lung cancer is the most common cancer in the world accounting for
      17.6% cancers worldwide. The AAR i n I ndian population varies f r om 0.98-15.55.
      The aim of t he present study was to analyze areduction in neoadjuvant
      chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA
      and III B) using Wobe Mugos E and its evaluation using micronuclei as a
      cytogenetic marker. Micronuclei, which are cytoplasmic fragments of DNA, have
      been used as a biological dosimeter to assess DNA damage. MATERIAL AND METHODS:
      Fourty patients of locally advanced NSCLC were randomized into two study groups
      between 2001-2003. One group received neoadjuvant chemotherapy using Cisplatin
      and Etoposide. The other group received neoadjuvant chemotherapy using Cisplatin
      and Etoposide along with Wobe Mugos E which is a proteolytic enzyme preparation.
      A study of micronuclei frequency was done pre and post chemotherapy in both
      groups. RESULTS: Thirty eight patients were available for final evaluation.
      Anemia was the most common hematological toxicity observed. Nausea and vomiting
      were the most common non -hematological toxicity seen. Wobe Mugos E was found to
      reduce the incidence of leucopenia (p = 0.005), nausea (p=0.004), vomiting (p=
      0.003), sensory neuropathy (p = 0.032) and treatment related depression (p=
      0.005). A reduction in micronuclei was seen in patients in patients on Wobe Mugos
      E. (p =0.01). CONCLUSION: Neo-adjuvant chemotherapy related acute toxicity is a
      major problem in patients with advanced lung cancer. A reduction in micronuclei
      frequency shows Wobe Mugos E to be effective in reducing chemotherapy related
      acute toxicity.

PMID- 16800344
TI  - Efficacy of HIV PCR techniques to diagnose HIV in infants born to HIV infected
      mothers--an Indian perspective.
AB  - AIM: To determine the efficiency of HIV DNA PCR (qualitative) and HIV RNA PCR
      (quantitative) to detect or rule out HIV infection in infants born to HIV
      infected mothers. SETTING: Pediatric and perinatal HIV clinic in a tertiary
      pediatric hospital. STUDY DESIGN: Prospective study METHODS AND MATERIALS: 52
      infants born to HIV positive mother were tested for HIV infection by HIV DNA PCR
      or HIV-1 viral load from 1.5 to 7 months of age. Their HIV status was confirmed
      by an HIV ELISA test at 18 months of age. RESULTS: Of the 36 patients tested by
      HIV DNA PCR test, 15 patients (41.8%) had a positive test and 21 patients (58.2%)
      had a negative test. 12 patients (80%) had a false positive test (80%) and no
      patient had a false negative test. Sensitivity of HIV DNA test 100% with
      specificity of 53.9%. Of the 18 patients tested by HIV viral load, 17 patients
      (94.4%) had a negative test and 1 patient (5.6%) had a positive test. No patient
      had a false negative or false positive test. Sensitivity and specificity of HIV
      viral load was 100%, which was statistically significant (p=0.0004). CONCLUSION:
      HIV-RNA PCR (quantitative) is highly specific and sensitive test for diagnosing
      and excluding perinatal HIV infection in children in India.

PMID- 16800345
TI  - Calcified guinea worms in breast.

PMID- 16800346
TI  - Cutaneous histoplasmosis in acquired immunodeficiency.

PMID- 16800347
TI  - Imatinib mesylate: A designer drug.
AB  - Molecularly targeted therapy is a novel approach in cancer treatment. Imatinib, a
      specific tyrosine kinase inhibitor, since its inception in 1990s, has become the
      first-line drug in management of chronic myelogenous leukemia (CML) chronic
      phase. It has also shown promising results in treatment of gastro-intestinal
      stromal tumors, clonal eosinophilic disorders and Philadelphia chromosome
      positive acute lymphatic leukemia. The efficacy of imatinib has geared up further
      research into development of designer drugs with molecular targets. This review
      gives a comprehensive description of the development, biology, utility, dosing,
      and limitations of imatinib mesylate.

PMID- 16800348
TI  - Medical philately (medical theme on stamps). Paracelsus (1493-1541).

PMID- 16800349
TI  - Exjade (ICL 670): A new oral iron chelator.
AB  - ICL670(deferasirox) is a tridentate oral iron chelator that has shown high
      efficacy and theraputic safety in preclinical and currently ongoing phase III
      clinical evaluation. The drug has been just approved by US FDA for use in iron
      loading anaemias. It is an ideal once-daily oral chelator, the effective dose of
      which is between 20 and 40 mg/kg. Iron is chelated & excreted almost exclusively
      via the feces. This is a major advance in the field of iron chelation.

PMID- 16800350
TI  - API TB Consensus Guidelines 2006: Management of pulmonary tuberculosis, extra
      pulmonary tuberculosis and tuberculosis in special situations.
AB  - INTRODUCTION: The World Health Organization (WHO) has declared Tuberculosis (TB)
      a global emergency in 1993. Prevalence of TB and Human Immunodeficiency Virus
      (HIV) co-infection worldwide is 0.18% and about 8% TB cases have HIV infection.
      Effective chemotherapy has been available for treatment of TB for over 50 years
      now. In World Health Organization (WHO)-International Union Against Tuberculosis
      and Lung Disease (IUATLD) Working Group Global Anti-Tuberculosis Drug Resistance
      Surveillance (1994-1997), the incidence of MDR TB in Delhi was found to be 14%,
      of which primary multi-drug resistance was only 1.4%, indicating that most of MDR
      TB is acquired as a result of poor chemotherapy. DIAGNOSIS OF TB: Since TB is an
      infectious disease caused by Mycobacterium (M) tuberculosis the diagnosis of TB
      should (as far as possible) be by demonstration of M. tuberculosis on culture or
      acid-fast bacilli (AFB) on smear examination. The World Health Organization (WHO)
      has strongly recommended sputum smear examination as the preferred screening test
      and suggests examination of 3 deeply coughed out sputum samples - spot sample on
      day 1, overnight sample and a spot sample in the morning on day 2. Recently it
      has been shown that sputum smear positivity is greater than 90% where greater
      than 5 ml of sputum is used for smear diagnosis of pulmonary TB. Culture of M.
      tuberculosis is the gold standard for diagnosis of TB. Culture of mycobacteria is
      a much more sensitive test than smear examination and has been estimated to
      detect 10-100 viable mycobacteria per ml of sample and in case of active disease
      they are found to be 81% sensitive and 98.5% specific. Culture methods are also
      required for further drug sensitivity testing in cases of suspected drug
      resistant cases. Isoniazid and rifampicin resistance can be reliably measured;
      resistance to pyrazinamide, ethambutol, and streptomycin is more difficult due to
      limitations of technique. The therapeutic index for a given drug is low for
      certain second-line drugs such as ethionamide, cycloserine, viomycin and para
      amino salicylic acid (PAS) and it leads to misinterpretation of results due to
      failure to distinguish between sensitive and resistant strains. Misdiagnosis of
      MDR-TB due to laboratory related errors has been reported recently. MANAGEMENT OF
      TB: Chemotherapy of TB consists of prevention of infection, also called primary
      chemoprophylaxis, when isoniazid 5 mg/kg is given to prevent infection in newborn
      infants of infectious mothers till mother is sputum smear positive (2-3months).
      Treatment of latent tuberculosis, also called secondary chemoprophylaxis, when
      isoniazid 5 mg/kg is given for 6 months to prevent disease in infected persons
      (asymptomatic MT positive individuals) and treatment of disease with Short Course
      Chemotherapy (SCC), as per WHO categories. Essential anti-tuberculosis (ATT)
      drugs Isoniazid (H), Rifampicin (R), Ethambutol (E), Pyrazinamide (Z) and
      Streptomycin (S) are the essential first line anti-tuberculosis drugs. Anti TB
      regimen consists of two phases: an initial intensive phase (IIP) and a
      continuation phase (CP). Best effective SCC for treatment of TB, for adults and
      children, for pregnant and lactating females, for cases associated with diabetes
      mellitus and HIV infection, for cases with pre-existing liver diseases (but
      normal liver functions) and mild renal failure is 2EHRZ, 4HR given daily or
      thrice weekly. Higher dose SCC intermittent therapy given in thrice weekly
      (2E3H3R3Z3, 4H3R3) has now been advocated by WHO and implemented by the Revised
      National TB Control Programme. DOTS, directly observed therapy short course,
      where the patient takes the drugs under the direct observation (DO) of a health
      worker to ensure regularity of consumption of drugs. Fixed dose combinations
      (FDCs) drugs consisting of two or three antituberculosis medications, provide a
      realistic and welcome alternative to DO that minimizes the opportunity for a
      patient to selectively take only a single medication. MANAGEMENT OF TB IN SPECIAL
      SITUATIONS: Pregnancy: All drugs, that is, rifampicin, isoniazid, ethambutol, and
      pyrazinamide can be used during pregnancy. Streptomycin is not given due to
      ototoxicity to the fetus. Prophylactic pyridoxine in the dose of 10mg/day is
      recommended along with ATT. Diabetes mellitus: The drug regimen is same as in
      nondiabetic. Strict control of blood glucose is mandatory. Also, doses of oral
      hypoglycemic agents may have to be increased due to interaction with Rifampicin.
      Prophylactic pyridoxine is indicated. Renal failure: Dosages may have to be
      adjusted according to the creatinine clearance especially for streptomycin,
      ethambutol and isoniazid. In acute renal failure, ethambutol should be given 8
      hours before hemodialysis. In post renal transplant patients: Rifampicin
      containing regimens are avoided as rifampicin causes increased clearance of
      cyclosporin. Pre-existing liver disease: In stable disease with normal liver
      enzymes, all anti-tuberculous drugs may be used but frequent monitoring of liver
      function tests is required. Treatment in unconscious patient (patients unable to
      swallow): If patients are fed by Ryle's tube or gastrostomy tube, usual doses and
      drugs may be powdered and administered avoiding feeds 2-3 hours before and after
      the dose. In cases where enterostomy has been performed or parenteral nutrition
      is being used, intramuscular streptomycin and isoniazid and intravenous
      quinolones may be used and switch to oral therapy once oral feed resume.
      Treatment of TB with HIV co-infection: In early stages the presentations of TB in
      TB-HIV co-infection is the same as HIV negative but in late stages extra
      pulmonary and dissemination are common. The usual short course chemotherapy is
      indicated in HIV positive patients. The response is usually good but relapse is
      frequent. After initiating ATT or anti-retroviral therapy (ART) worsening of
      preexisting lesions or appearance of new lesions is seen, "paradoxical response"
      or "immune reconstitution phenomenon". Multidrug resistant TB can occur due to
      poor compliance to ATT due to behavioural pattern, increased incidence of side
      effects and malabsorption of drugs due to associated diarrhea. ART for HIV,
      containing protease inhibitors (PI) and non-nucleoside reverse transcriptase
      inhibitors (NNRTI) cannot be used along with R, as R induces metabolism of PI and
      reduces the efficacy. The various options are i) to postpone anti-retroviral
      therapy ii) to use no PI or NNRTI containing anti-retroviral combinations iii) to
      use certain PI/ and/or NNRTIs with modification in doses iv) Efavirenz (EFZ) or
      Saquinavir with Ritonavir, without the need to adjust the doses v) to use non R
      regimens e.g. 2SHEZ+10HE MANAGEMENT OF MDR TB: As far as possible treatment of
      MDR TB should be referred to specialized units with facilities for quality
      controlled DST and experienced in handling such cases. If such referrals are not
      possible, one must remember that while initiating or revising therapy for MDR-TB,
      drugs selection must rely on prior treatment history, results of susceptibility
      testing and an evaluation of the patient's adherence.

PMID- 16800351
TI  - Acute axonal polyneuropathy in an unventilated patient with sepsis.
AB  - Critical Illness Polyneuropathy (CIP) represents an acute axonal neuropathy that
      develops during treatment of severely ill patients and remits spontaneously once
      the critical condition is under control. Except for differences in the
      predisposing causes, it is difficult to distinguish CIP from axonal Guillain
      Barre Syndrome (GBS) on purely clinical grounds. We describe a 70 years lady who
      developed acute axonal polyneuropathy two weeks following snakebite. She
      developed this in the background of sepsis but never required ventilatory
      support. The difficulties in differentiating CIP from axonal GBS are discussed.
      The hypothesized overlap between both these syndromes is also reviewed.

PMID- 16800352
TI  - Macrophage activation syndrome.
AB  - Macrophage Activation Syndrome is a rare and potentially fatal disease, to be
      considered in patients with a SIRS like clinical presentation. Falling ESR and
      hyperferritinemia in the appropriate clinical setting can be the greatest clues.
      We report a case in which a female admitted with fever and rash, initially had
      systemic inflammatory response syndrome (SIRS) like clinical presentation, but
      eventually proved to be a rare case of fatal Macrophage Activation Syndrome.

PMID- 16800353
TI  - Renal abscess.
AB  - This study analyses the pre-disposing factors, diagnostic modalities, therapeutic
      options and prognostic factors involved in 7 subjects with renal abscess. Most
      often they presented with high fever and flank pain. USG and CT were used to
      establish the diagnosis. Urine culture yielded organisms in five cases and hence
      empirical antibiotic therapy for Gram-negative organism was offered. Complicated
      abscess in our series carried high mortality especially in immuno suppressed and
      cachectic patients.

PMID- 16800354
TI  - Sudden death due to cardiac toxoplasmosis.
AB  - The recognition of cardiac toxoplasmosis has increased in patients with acquired
      immunodeficiency syndrome. The functional consequences of toxoplasmosis of heart
      vary considerably depending on the intensity of inflammatory reaction, the extent
      of involvement of myocardial muscle fibers by necrosis and intramyocytic presence
      of tachyzoites of Toxoplasma gondii. This report describes a case of toxoplasma
      myocarditis that lead to fatal cardiac arrest. To the best of our knowledge, this
      is the first reported case of cardiac toxoplasmosis in the Indian literature,
      which has manifested as sudden death.

PMID- 16800355
TI  - Papillon Lefevre syndrome.
AB  - Papillon Lefevre syndrome is a rare disease characterized by skin lesions caused
      by palmar-plantar hyperkeratosis, and severe periodontal destruction involving
      both the primary and permanent dentitions. It is transmitted as an autosomal
      recessive condition and consanguinity of parents is evident in about one-third of
      cases. Pyogenic liver abscess is an increasingly recognized complication. We
      report a new case of this association and review the current literature.

PMID- 16800356
TI  - Melnick- needles osteodysplasty presenting with quadriparesis.
AB  - Melnick-Needles syndrome or osteodysplasty, a monogenic heritable bone dysplasia,
      is characterized by a typical facies and characteristic radiological findings.
      Less than 70 well-documented cases have been reported in literature; most of them
      were sporadic. We report the first case from Eastern India in an adolescent male,
      who had cranio-vertebral junction anomalies and presented with spastic
      quadriparesis at the age of 13 years.

PMID- 16800358
TI  - Significance of noseclips during spirometric maneuver in patients with COPD.

PMID- 16800357
TI  - Organophosphorus poisoning: a study on the effectiveness of therapy with oximes.

PMID- 16800359
TI  - Providing children with the quality dental care they deserve.

PMID- 16800360
TI  - The impact of fixed orthodontic appliances on daily life.
AB  - OBJECTIVE: i) To develop a measure of the impact of fixed orthodontic appliances
      on daily life. ii) To assess the impact of fixed appliances over time after
      initial appliance placement. iii) To investigate factors that may influence the
      impact of fixed appliances (age, gender and socioeconomic status). RESEARCH
      DESIGN: Questionnaire. CLINICAL SETTING: University Dental Hospital and Hope
      Hospital, Manchester. SAMPLE: Sixty-six patients, whose orthodontic appliances
      had just been placed. Twenty-eight patients whose orthodontic appliances were in
      place for at least six months were used for the reliability study. METHOD: The
      Impact of Fixed Appliances Questionnaire was developed using standard qualitative
      methods and pre-tested on 10 patients. This resulted in a questionnaire with nine
      conceptual impact sub-scales: aesthetic, functional limitation, dietary, oral
      hygiene, maintenance, physical, social, time constraints and travel/cost. The
      questionnaire was piloted on 66 patients, at the first, second and third visits
      after their fixed appliance had been placed, to assess the impact of fixed
      appliances over time. Questionnaire reliability, over a one-month time interval,
      was assessed on 40 patients who had been in treatment for at least six months.
      MAIN OUTCOME MEASURE: Impact of fixed appliances on daily life. RESULTS: The
      internal reliability of the questionnaire ranged from moderate to very good
      (Cronbach's alpha 0.56-0.89). Test-retest reliability was stable for most
      subscales (intra-class correlation coefficient 0.26-0.65). The questionnaire was
      said to have face validity and also content validity because of the method of
      questionnaire development through interviewing children with fixed appliances.
      None of the subscales scores reduced over time except aesthetic impact (p< 0.05)
      but this was probably not a clinically significant change. Age was the
      predominant variable to influence the impact of fixed appliances with younger
      children being less affected during their daily life (p<0.05). CONCLUSIONS: The
      questionnaire developed in this study is a reliable tool for assessing the impact
      of fixed appliances on the daily life of children. It is unlikely that the impact
      of fixed appliances on daily life reduces as the patient progresses through
      treatment. Younger patients are probably more adaptable to treatment with fixed
      appliances, in terms of reduced impact on daily life, so arguably treatment
      should be started as early as possible. This information could also be used to
      educate, reassure and motivate patients at the start of treatment.

PMID- 16800361
TI  - Service quality implications of dental undergraduate outreach teaching for
      Primary Care Trusts in England, UK.
AB  - OBJECTIVE: Primary Care Trusts (PCTs) assumed new responsibilities for dentistry
      in 2005. In dental education it has been suggested that more emphasis is made of
      primary care outreach schemes. The paper considers the service quality
      implications of dental outreach teaching for PCTs with particular reference to
      access and acceptability. RESEARCH DESIGN AND CLINICAL SETTING: A pilot of
      outreach teaching for Manchester undergraduates in relation to adult dental care
      began in 2001. Six groups of eight students, working in pairs, spent one day per
      week in one of three community dental clinics in socially deprived areas. The
      evaluation of the first year used data from 908 patient treatment summaries, 139
      patient questionnaires, and records of patient attendance. MAIN OUTCOME MEASURES:
      Access and acceptability measured by patients' demographic characteristics,
      patients' attendance at the clinics; patients' reasons for attendance, use of
      services and satisfaction with the service. RESULTS: In terms of access, the new
      service was used by local patients. Their main reasons for attending were
      convenience, a dental problem, free treatment, lack of access to a dentist, and
      lay referral. Some 41 percent attended initially because of an emergency, 30
      percent said that if they had not attended the clinic they would have gone
      nowhere or did not know where they would have gone, and 49 percent had not
      attended a dentist for more than two years. In terms of acceptability most
      patients were positive about being treated by a student, 96 percent thought the
      quality of care excellent or good, and the same percentage said they would return
      to the clinic. The main areas of criticism were waiting times and appointments.
      CONCLUSIONS: Students can provide an accessible and acceptable local primary care
      dental service for adult patients in socially deprived areas as part of their
      undergraduate learning, and in a way that complements the existing services.

PMID- 16800362
TI  - Prevalence of hypodontia and hyperdontia in paedodontic and orthodontic patients
      in Budapest.
AB  - Various publications have reported the prevalence of accessory teeth to be
      between 1 and 3%. In contrast, hypodontia has a much higher prevalence. In the
      current work, the authors studied OP radiographs on 2,219 patients aged 6 to 18
      years who presented at the Department of Paedodontics and Orthodontics at
      Semmelweis University in Budapest (patients with systemic disease were excluded).
      The examined radiographs revealed a prevalence of accessory teeth of 1.53%. The
      sequence of prevalence was as follows: mesiodens > second incisor > first
      incisor. 77.5% of the accessory teeth were located in the upper jaw, with 97.5%
      of those being present in the incisor region. Hypodontia was detected in 326
      patients (14.69%); missing wisdom germs were not considered. The sequence of
      prevalence of missing germ was as follows: upper second incisor > lower second
      premolar > upper second premolar > lower first incisor. Hypodontia in the molar
      region was observed in 15 cases (0.68%). The prevalence of oligodontia was 1.04%.

PMID- 16800363
TI  - Psychometric properties of the Arabic version of the Dental Cognition
      Questionnaire.
AB  - OBJECTIVES: This study investigates the psychometric properties of the Arabic
      version of the Dental Cognitions Questionnaire (DCQ), especially evolved for the
      purpose. STUDY DESIGN: The DCQ was administered to a total of 1,266 Kuwait
      University undergraduate students, 348 males and 918 females, achieving high
      internal consistency (alpha = .87). RESULTS: Factor analysis resulted in the
      selection of eight factors each for males and females from the DCQ. The Arabic
      DCQ significantly and positively correlated with measures of dental fear (ADFI
      and DFS), dental anxiety (CDAS and DAST) and dental opinion (DO). Significant
      gender differences were observed with regard to 16 items of the DCQ. Overall,
      females showed greater DCQ believability than males. CONCLUSION: The DCQ
      correlates with dental fear more than dental anxiety. The study provides insights
      into factor structure of the Arabic Version of the DCQ, with significant
      correlation between scores on the DCQ and CDAS, suggesting that DCQ could be used
      as a reliable research tool.

PMID- 16800364
TI  - Dental caries experience in preschool children in Veneto region (Italy).
AB  - OBJECTIVES: The aim of this study was to assess the dental caries experience in
      deciduous dentition among preschool children attending nursery-schools in the
      area of Ulss n.15 of Veneto Region (Italy). BASIC RESEARCH DESIGN AND
      PARTICIPANTS: A cross sectional survey in maternal schools in an area of North
      East of Italy was carried out between October 2002 to May 2003 enrolling 1,006 2
      6 year-old children randomly selected. WHO diagnostic criteria for dental caries
      were adopted; dmft and SiC indices were used to measure the severity of the
      disease. In this paper the "umbrella" term ECC to define caries in primary
      dentition prior to eruption of permanent teeth (Horowitz, 1998) was used as well.
      RESULTS: ECC prevalence and mean dmft by age were: 3 years: 13.28% and 0.53 (SD
      +/- 1.83); 4 years: 18.95 % and 0.83 (SD +/- 2.24) ; 5 years: 26.9% and 1.34 ( SD
      +/- 2.8). SIC index values were 1.6 at 3 years, 2.4 at 4 years and 4 at 5 years.
      CONCLUSIONS: The prevalence of dental caries increased with age: the mean dmft
      increased 2 1/2 times (0.53 to 1.34) and the percentage of children affected by
      caries doubled (13.28% to 26.9%) between ages 3 and 5 years. Comparing the data
      for 4 year-old children with those of two surveys carried out in the same area in
      the last two decades, it is concluded that as in the other industrialised
      countries, dental caries in preschool children of this area of North-East of
      Italy has declined.

PMID- 16800365
TI  - Improving access to dental care in East London's ethnic minority groups:
      community based, qualitative study.
AB  - There are few studies of access to dental care in ethnic minority groups which
      have compared their findings with those reported by the general adult population.
      Furthermore, studies have focused on either the younger or older members of these
      communities. AIM: This study aimed to identify barriers to the uptake of primary
      dental care in East London, to identify any variation in responses from the
      general adult population and to report ideas to improve access to primary dental
      care expressed by the participants. METHODS: A qualitative study using community
      based participatory methods was adopted. Data were generated through purposefully
      sampled focus groups and analysed using a grounded approach. SETTING: East London
      (UK), 2001. PARTICIPANTS: 68 volunteers aged 18-40 years, from the Bangladeshi,
      Indian, Black Caribbean communities and general adult population. RESULTS: Three
      inter-related themes were found to influence views on access: the structure of
      primary dental care, cost and anxiety. There was little evidence of differences
      in barriers to access based on ethnicity alone, reflecting the role of factors
      such as social class. Adult volunteers with young families enabled a wider
      perspective on barriers to access to be achieved, particularly with respect to
      the impact of the cost of dental care on family budgets. Proposals for reducing
      the barriers to accessing primary dental care were identified. These addressed a
      perceived need to extend services through outreach activity, develop
      communication skills within primary dental care practice and liaise with other
      primary health care services. CONCLUSION: This focus group study has confirmed
      the existence within East London's ethnic minority groups of barriers to
      accessing primary dental care reported within the general population for some
      time. That these responses are alike may be accounted for by the common levels of
      social disadvantage experienced. The rapid appraisal process enabled the
      identification of proposals to reduce access barriers. These are being
      implemented and their effectiveness in reducing barriers to accessing primary
      dental care remains to be established.

PMID- 16800366
TI  - The unequal burden related to the risk of oral cancer in the different regions of
      the Kingdom of Saudi Arabia.
AB  - OBJECTIVES: To estimate the burden and risk of oral cancer in Saudi Arabia and
      highlight differences between regions. METHODS: Using the National Cancer
      Registry Saudi Arabia, data was collated on numbers of cases of oral cancer (1996
      1998) by site, age group, gender and region, plus relative frequencies of all
      cancer cases. Using Globocan, age-standardised rate (ASR) of oral cancer in Saudi
      Arabia was compared with five other neighbouring countries in the region.
      RESULTS: A total of 208 lip, mouth and tongue cancers for men and 209 for women
      were reported to the registry during this period. ASR of oral cancer was
      1.81/100,000 for males and 2.13/100,000 for females. It was ranked 15th most
      common cancer for males and 11th for females, with a ratio of 1:1 and median age
      at diagnosis of 62 years. Very wide regional disparities in the incidence of oral
      cancer were found, with an almost thirty-fold difference in ASR between the
      regions with the lowest and highest rates. Jizan Region had the highest ASR
      (6.2/100,000 for males and 9.82/100,000 for females). Here oral cancer was ranked
      2nd for males and 1st for females, with a ratio of 0.73:1 and the median age at
      diagnosis for females was lower. The third highest ASR (4.48/100,000) was found
      in females in Najran. In these two high incidence regions oral cancer was
      commonly reported on the gingiva. CONCLUSIONS: Overall the burden and risk of
      oral cancer in Saudi Arabia are not large. However, cancer of the oral cavity is
      a significant public health problem for the residents of Jizan and the women of
      Najran. Saudi females in both these regions have a higher burden of oral cancer.

PMID- 16800367
TI  - Can oral health promotion help develop masticatory function and prevent dental
      caries?
AB  - OBJECTIVE: In an effort to promote adequate development of the masticatory system
      and prevent dental diseases, the Oral Health Promotion Project (OHPP), which
      focuses on diet, was started in 1984. The intervention was carried out over eight
      years and then followed up for a further nine years, in a district with no
      regular dental service, on Miyako Island, Okinawa, Japan. The aims of this study
      were to evaluate the project's effect on dental caries and masticatory function.
      RESEARCH DESIGN: Longitudinal data on the complete deciduous dentitions(IIA) at
      age 4 (n=163) and on the permanent dentition (IVA) at age 13-15 (n=112) were
      compared to control age-matched groups, aged 4 (n=105) and aged 13-15 (n=70). The
      control data were collected from a neighbouring district. Instructions on diet
      were gradually introduced to those in charge of the subjects' food regimes.
      RESULTS: Mothers reported that children born after the OHPP was begun took less
      snacks and caloric drinks (p<0.001) and more fibre-rich food (p<0.05) than those
      who born before the start of the project. The number of carious teeth decreased
      significantly among subjects born after the start of the project. The masticatory
      function was summarized in one factor using chewing performance, bite force,
      muscle activity duration time (using EMG) and mean amplitude of muscle activity.
      The factor score was higher for those born after 1984 than for those born in 1981
      1983 and for those in the control district (GLM, p<0.001). CONCLUSION: It is
      suggested that OHPP can promote the masticatory function and prevent dental
      caries, but that it would be crucial to begin intervention soon after birth.

PMID- 16800368
TI  - The equity of access to primary dental care for children in the North East of
      England.
AB  - OBJECTIVES: To determine the equity of access to dental care from general dental
      practitioners for children aged 0 to 17 years. BASIC RESEARCH DESIGN: Postcode
      data was obtained from the Dental Practice Board for children registered with an
      NHS dentist. There were 146,180 children aged 0 to 17 years old resident in the
      study area, these were mapped to their ward of residence. The child registration
      rate for wards was calculated, using 2001 census data. The level of deprivation
      for wards was obtained using a standard indicator, the Index of Multiple
      Deprivation. SETTING: The Durham and Tees Valley Strategic Health Authority area
      in the North East of England. The Authority has a population of 1.13 million, of
      which 260,000 were aged 0 to 17, in 2001. There are approximately 170 dental
      practices in the Authority area contained in 251 Wards. RESULTS: The range of
      child registration rates in wards was, 11% to 90%. There was a significant
      negative association between the number of children registered with a dental
      practice and increasing deprivation. For every 10 point increase in the
      deprivation score the probability of registration reduced by 5% of the overall
      rate. The probability of registration reduced less in those wards with a dental
      practice compared to those without a dental practice with increasing deprivation.
      CONCLUSIONS: There are significant inequalities in access to dental care.
      Children living in deprived wards access general dental practices less than those
      living in wealthier wards. The location of dental practices may reduce
      inequalities in access.

PMID- 16800369
TI  - Improving the oral health of young children through an evidence-based approach.

PMID- 16800370
TI  - [Brain natriuretic peptide and QRS duration as a predictor for cardiac events in
      patients with heart failure].
AB  - OBJECTIVES: Brain natriuretic peptide (BNP) and QRS duration have been reported
      as independent predictors for cardiac events in patients with heart failure. The
      present study investigated the relationships between BNP and QRS duration to
      assess the prognostic value in patients with heart failure. METHODS: We
      prospectively examined 93 patients presenting to our emergency department with
      heart failure between April 2000 and April 2003 (age 69 +/- 13 years, 53 males,
      40 females). BNP level and QRS duration were measured after treatment for heart
      failure. The efficacy end point was the composite incidence of sudden death,
      death for progressive heart failure, or readmission for worsening heart failure.
      RESULTS: During the mean follow-up period of 720 +/- 470 days, cardiac events
      occurred in 35 patients (sudden death in 6, death for progressive heart failure
      in 9, and readmission for worsening heart failure in 20). BNP level was almost
      equally higher in the three groups with cardiac events (mean +/- SEM; sudden
      death: 348 +/- 128 pg/ml, death for progressive heart failure: 390 +/- 97 pg/ml,
      readmission for worsening heart failure: 354 +/- 79 pg/ml) than in patients
      without cardiac events (213 +/- 34 pg/ml). In contrast, QRS duration was
      exclusively prolonged in patients with sudden death(mean +/- SEM, 125 +/- 10
      msec) compared with the remaining three groups (death for progressive heart
      failure: 100 +/- 5 msec, readmission for worsening heart failure: 103 +/- 4 msec,
      no cardiac events: 108 +/- 3 msec). No relationship was found between BNP level
      and QRS duration in all patients with heart failure (Spearman r = 0.13, p =
      0.22). CONCLUSIONS: Increased BNP level was associated with poor prognosis
      irrespective of mode of cardiac events, and prolonged QRS duration was related to
      sudden death in our cohort with heart failure. The combination of BNP level and
      QRS duration may have adjunctive value in predicting the prognosis in patients
      with heart failure.

PMID- 16800371
TI  - [Efficacy of additional low-dose carvedilol in maintenance hemodialysis patients
      with asymptomatic left ventricular systolic dysfunction].
AB  - OBJECTIVES: The effects of additional low-dose carvedilol were evaluated in
      maintenance hemodialysis patients with asymptomatic left ventricular systolic
      dysfunction for 2 years. METHODS: Thirteen hemodialysis patients with
      asymptomatic left ventricular systolic dysfunction (left ventricular ejection
      fraction < 45%) were given carvedilol (5 mg) at every hemodialysis period.
      Echocardiography and brain natriuretic peptide level were measured at baseline,
      3, 6, 12, and 24 months after treatment. RESULTS: There was no major complication
      with 5 mg of carvedilol during 24 months. Two-year echocardiographic data
      revealed a significant attenuation of pathophysiologic remodeling, with smaller
      left ventricular end-diastolic volume (170 +/- 33 to 157 +/- 26ml, p < 0.0001)
      and higher left ventricular ejection fraction (38 +/- 6% to 49 +/- 5%, p <
      0.0001) after 6 months. In addition, brain natriuretic peptides were
      significantly decreased after 6 months (378 +/- 174 to 181 +/- 122 pg/ml, p <
      0.0001). CONCLUSIONS: Additional low-dose carvedilol therapy in maintenance
      hemodialysis patients with asymptomatic left ventricular systolic dysfunction has
      beneficial effects on cardiac function, geometry and neurohormonal status.
      Carvedilol is excreted by the liver and there were minimal fluctuations between
      hemodialysis, so, theoretically, drug dosage of the agent should be the same as
      in non-hemodialysis patients. Our results conflicted with prior studies, possibly
      caused by decreased circulation volume or plasma albumin level of hemodialysis
      patients, which would represent the effect of other drugs such as digoxin. Dosage
      adjustment and monitoring of drug plasma levels are required if the usual dosage
      of carvedilol is not tolerated in maintenance hemodialysis patients with
      asymptomatic left ventricular systolic dysfunction.

PMID- 16800372
TI  - [Immunoglobulin stabilizes plaque formation in experimental atherosclerosis].
AB  - OBJECTIVES: Immunoglobulin treatment is known to suppress atherosclerosis in
      apolipoprotein E-deficient mice. In addition, immunoglobulin inhibits
      atherosclerosis via the Fc receptors. However, the effect of immunoglobulin
      treatment at the advanced stage of atherosclerosis is still unclear. This study
      examined the effects of immunoglobulin on apolipoprotein E-deficient mice at the
      advanced stage of the disease. METHODS: Atherosclerosis was induced in mice fed a
      high-fat diet containing 0.3% cholesterol. After confirming the presence of
      atherosclerotic lesions at 11 weeks, mice were intraperitoneally treated with
      injections of either intact type of immunoglobulin (1 g/kg/day) or F (ab') 2
      fragments of immunoglobulin (1 g/kg/day) on alternate days over 4 weeks. Oil red
      O staining and immunohistochemical staining with CD4+ cells were performed of the
      aorta, and atherosclerotic lesions was evaluated and compared between the groups.
      RESULTS: Fatty streak lesion was significantly suppressed by intact
      immunoglobulin compared with saline, and inflammatory cell infiltration and
      expression of CD4+ cells were less in mice treated with intact immunoglobulin
      compared with the control. CONCLUSIONS: Immunoglobulin treatment even at the
      advanced stage of atherosclerosis suppressed the development of fatty lesions and
      may stabilize atherosclerotic plaques by inhibiting inflammatory cell expression.
      Immunoglobulin suppression of atherosclerosis was confirmed to act via the Fc
      receptors.

PMID- 16800373
TI  - Tricuspid valve stenosis related to subvalvular adhesion of pacemaker lead: a
      case report.
AB  - Endocardial pacemaker leads may cause tricuspid valve regurgitation, but only
      four cases of tricuspid stenosis without endocarditis have been reported. A 77
      year-old woman had received three endocardial leads when aged 44, 57, and 72
      years. One lead pushed up the septal leaflet of the tricuspid valve from below
      the valve, then adhered to the leaflet, and was positioned against the
      ventricular septum. Tricuspid valve stenosis and moderate regurgitation were
      separately detected by transthoracic echocardiography. The tricuspid valve
      orifice area was 0.93 cm2 at cardiac catheterization. An excessive loop of a
      ventricular lead, especially a subvalvular loop, can cause opening limitation of
      the tricuspid valve, and the entangling of the lead in the subvalvular structures
      can easily induce reactive fibrosis and adhesions.

PMID- 16800374
TI  - [Regression of a large lipid-rich pool in the coronary artery during treatment
      with statin detected by intravascular ultrasound: a case report].
AB  - A 54-year-old man with unstable angina presented with severe stenosis of the
      middle segment of the left anterior descending coronary artery. Percutaneous
      coronary stent implantation and serial intravascular ultrasound (IVUS) were
      performed. IVUS detected a non-culprit coronary plaque with a large lipid-rich
      pool in the proximal segment of the left anterior descending coronary artery.
      Atorvastatin 10 mg/day was given to reduce his cholesterol level for 2 years
      after the stent implantation. This patient had no cardiac events, and the low
      density lipoprotein-cholesterol level reduced from 171 to 88 mg/dl at follow-up.
      Two-year follow-up IVUS examination revealed the reduction of plaque burden
      associated with regression of the lipid-rich pool size. This case may indicate
      that statin could contribute to the regression of lipid-rich plaque and to the
      stability of coronary plaque.

PMID- 16800375
TI  - [Repeated percutaneous transluminal septal myocardial ablation leads to reduction
      of left ventricular outflow-tract pressure gradient in hypertrophic obstructive
      cardiomyopathy: a case report].
AB  - A 61-year-old man with hypertrophic obstructive cardiomyopathy was treated twice
      with percutaneous transluminal septal myocardial ablation (PTSMA). The first
      procedure improved the left ventricular outflow tract pressure gradient (LVOTG)
      from 148 to 48 mmHg and the New York Heart Association (NYHA) class from III to
      II in a week. However, the LVOTG increased to 197 mmHg and the NYHA class
      worsened to III within 3 months. In spite of medical treatment with beta-blocker,
      syncope attack occurred suddenly. Repeated PTSMA was performed. Just after the
      second procedure, the LVOTG did not decrease. However, the LVOTG decreased to 81
      mmHg and the NYHA class improved to II with 3 months. The different response of
      pressure gradient in the acute and chronic phase with repeated PTSMA was
      interesting.

PMID- 16800376
TI  - [Evaluation of coronary artery Doppler by transthoracic approach].

PMID- 16800377
TI  - Mutator transposon in maize and MULEs in the plant genome.
AB  - Mutator (Mu) is by far the most mutagenic plant transposon. The high frequency of
      transposition and the tendency to insert into low copy sequences for such
      transposon have made it the primary means by which genes are mutagenized in maize
      (Zea mays L.). Mus like elements (MULEs) are widespread among angiosperms and
      multiple-diverged functional variants can be present in a single genome. MULEs
      often capture genetic sequences. These Pack-MuLEs can mobilize thousands of gene
      fragments, which may have had a significant impact on host genome evolution.
      There is also evidence that MULEs can move between reproductively isolated
      species. Here we present an overview of the discovery, features and utility of Mu
      transposon. Classification of Mu elements and future directions of related
      research are also discussed. Understanding Mu will help us elucidate the dynamic
      genome.

PMID- 16800378
TI  - Somatic cell and sperm cell cytogenetics in a patient with t(14; 21).
AB  - Approximately 15%-20% of clinically recognizable pregnancies end in spontaneous
      abortion. About half of the spontaneous abortions in the early stage of the
      pregnancy are due to chromosomal abnormalities. Using GTG chromosome banding and
      dual-color fluorescence in situ hybridization (FISH) techniques, we determined
      the cytogenetic aberration in the husband of a couple with spontaneous recurrent
      abortions. Karyotype analysis showed 46, XX in the wife and 45, XY, -14, -21,
      +t(14; 21) in the husband. We studied the mechanism of formation of the abnormal
      chromosome with Robertsonian translocation between chromosomes 14 and 21 by FISH
      and flow cytometric sorting in the sperm cells. The result showed that 71% of the
      gametes were balanced and the remaining 29% were not. As a result, the couple was
      given genetic counseling.

PMID- 16800379
TI  - Association between a functional COMT polymorphism, mental retardation and
      cognition in Qinba area children.
AB  - Catechol-O-methyl transferase (COMT) plays an important role in the metabolism of
      neurotransmitters. Two alleles of the COMT gene as a result of a G/A transition
      in the exon 4 can lead to different COMT enzymatic activities. Much genetic
      research has revealed that this COMT functional polymorphism was related to human
      psychiatric disorders. Polymerase chain reaction (PCR) and restriction fragment
      length polymorphism (RFLP) methods were used to discern the relationships among
      the functional polymorphism of COMT, mental retardation (MR), and general
      cognitive ability of children. The results of the case-control analysis showed
      that there was no association between the frequencies of genotypes of COMT and MR
      (chi2=0.776, P>0.05) or between the frequency of COMT alleles and MR (chi2=0.335,
      P>0.05). COMT polymorphism was found in children whose intelligence quotient (IQ)
      was above 55. In normal children (IQ> or =85), the frequencies of high-activity
      allele COMTH and the homozygote genotype COMTHH were 60.98% and 79.28%,
      respectively. Both were higher than those of the borderline group (46.67% and
      70.67%, 0.10 > P>0.05). Therefore, the result of this study suggests that this
      functional polymorphism is not an important risk factor for MR, but the COMTHH
      genotype may have a positive effect on cognitive performance in normal children
      in the Qinba area.

PMID- 16800380
TI  - Correlation analysis between single-nucleotide polymorphism of malate
      dehydrogenase gene 5'-flanking region and growth and body composition traits in
      chicken.
AB  - Malate dehydrogenase (MD) is a key enzyme that plays an important role in energy
      metabolism. It catalyzes the oxidative decarboxylation of L-malate to yield CO2
      and pyruvate, while simultaneously generating NADPH from NADP+. The NADPH
      generated can be utilized in de novo synthesis of palmitate, which is the
      precursor molecule for the formation of other long-chain fatty acids. And high
      levels of MD will also activate muscle development. The current study was
      designed to investigate the effects of MD gene on growth and body-composition
      traits in chicken. The eighth generation population of Northeast Agricultural
      University broiler lines divergently selected for its abdominal fat and Northeast
      Agricultural University F2 resource population were used in the research.
      Polymorphisms were detected by DNA sequencing and PCR-RFLP method was then
      developed to screen the population. A single mutation at the position of the 235
      bp (Accession No. U49693) of MD 5'-flanking region was found. The correlation
      analysis between the polymorphism of the MD gene and growth and body composition
      traits was carried out using the appropriate statistic model. Least-square
      analysis showed that the BB genotype birds had much higher pectoralis major
      weight and percentage of pectoralis major than AA genotype birds (P<0.05). The
      abdominal fat weight, percentage of abdominal fat, the liver weight and
      percentage of liver weight of the AA genotype birds were much higher than those
      of BB genotype birds (P<0.05). These results indicate that MD gene is the major
      gene or is linked to the major gene that affects the growth and body composition
      traits in chicken.

PMID- 16800381
TI  - The developmental changes and effect on IMF content of H-FABP and PPARgamma mRNA
      expression in sheep muscle.
AB  - Male Kazak sheep and Xinjiang fine wool sheep of different ages were selected to
      investigate the developmental changes and effect on intramuscular fat (IMF)
      content of heart fatty acid-binding protein (H-FABP) and peroxisome proliferator
      activated receptor gamma (PPARgamma) mRNA expression in muscle. Longissimus
      dorsal muscle was sampled to measure IMF content; and total RNA was extracted to
      determine H-FABP and PPARgamma mRNA expression levels by real-time PCR. The
      results showed that: (1) The IMF content increased continuously with growing and
      showed significant differences (P<0.05) between ages in male Kazak sheep, but no
      such differences (P>0.05) existed in Xinjiang fine wool sheep. Furthermore, the
      IMF content in Kazak sheep was very much higher (P<0.01) than that of the other
      breed from day 30 to 90; (2) H-FABP mRNA expression level was the highest on day
      2 and showed significant differences (P<0.05) between ages in male Kazak sheep as
      well as in Xinjiang fine wool sheep. In the former breed, the expression reached
      the lowest point at day 30, and then rose continuously. But in the latter breed,
      it declined continuously from day 2 to 90, and then increased; (3) Significant
      differences (P<0.05) of PPARgamma mRNA expression between ages occurred in both
      breeds. In male Kazak sheep, PPARgamma mRNA expression declined from day 2 to 90,
      while in the other breed it increased continuously from day 2 to 60, but reached
      the lowest level at day 90, then increased; (4) In male Kazak sheep, the mRNA
      expression level of H-FABP was highly positively correlated (r=0.737, P<0.01)
      with IMF content from day 30 to 90, but that of PPARgamma was highly negatively
      correlated (r=-0.835, P<0.01) with IMF content from day 2 to 90.

PMID- 16800382
TI  - Relationship among H-FABP gene polymorphism, intramuscular fat content, and
      adipocyte lipid droplet content in main pig breeds with different genotypes in
      western China.
AB  - H-FABP(Heart fatty acid-binding protein), a member of FABP family, plays an
      essential role in long-chain fatty acid uptake and metabolic homeostasis. Its
      role in pig intramuscular fat content remains poorly understood, especially in
      local pig breeds in western China. In this study, the genetic variations of 5'
      upstream region and the second intron in porcine H-FABP gene were investigated by
      PCR-RFLP in 256 pigs including Duroc, Large White, Landrace, Neijiang, Rongchang,
      Bamei pig, Hanjiang Black, Hanzhong White, and the wild ones. The effect of H
      FABP gene on the IMF content was analyzed by the least square method. Lipid
      droplet morphology and content in adipocytes cultured from pigs with different H
      FABP genotypes, were studied by oil red O staining and a triglyceride assay kit.
      Results showed a Hinf I -RFLP in these eight pig breeds and wild pigs, among
      which Large white, Bamei pig, Hanjiang Black, Hanzhong White, and wild pigs
      presented with low polymorphism while the other breeds had intermediate
      polymorphism. There was no Hae III or Msp I -RFLPs in the four Chinese local pig
      breeds tested, but Duroc, Landrace, Large White, Hanzhong White and wild pig had
      polymorphism. Landrace, Large White and wild pigs had low levels of Hae III- and
      Msp I -RFLP, whereas others had intermediate polymorphism. H-FABP genotypes
      significantly affected the IMF content (P<0.05). The IMF content ordered by H
      FABP genotypes were HH>Hh>hh, DD<Dd<dd, and AA<Aa<aa. The genetic effect values
      were 3.89, 3.42, 3.17, 2.27, 2.49, 2.91, 2.28, 2.70, and 2.95, respectively. Fat
      deposition in adipocytes was stronger in the HH, dd and aa genotypes than in
      others. The results suggest that porcine meat quality may be improved by
      increasing the frequency of genotype aa-dd-HH in pig breeds.

PMID- 16800383
TI  - Isolation and characterization of OsGSTL1 promoter from rice.
AB  - OsGSTL1 gene was isolated from the rice genomic library. Semi-quantitative RT-PCR
      analysis demonstrated that the expression of the OsGSTL1 in rice was not induced
      by chlorsulfuron, ethylene, abscisic acid, salicylic acid, and methyl jasmonate.
      In order to investigate the cis-elements of OsGSTL1 promoter, the promoter
      regions with different lengths were fused to the beta-glucuronidase (GUS)
      reporter gene. All constructs were transformed into onion epidermal cells or A.
      thaliana plants to detect the expression patterns. In onion epidermal cells, the
      160 bp fragment and longer ones were functional for directing GUS expression. In
      transgenic A. thaliana, the 2,155 bp upstream region of OsGSTL1 gene directed the
      GUS expression only in cotyledon after germination, but not in the root of young
      seedlings. In the later seedling, the 2,155 bp upstream region of OsGSTL1 gene
      directed GUS expression in roots, stems, and leaves. However, the GUS gene
      directed by a 1,224 bp upstream fragment is expressed in all the checked tissues.
      These results suggest that the spatiotemporal expression response elements of
      OsGSTL1 existed in the 5'-upstream region between -2,155 and -1,224 bp.

PMID- 16800384
TI  - Identification of quantitative trait loci for ABA sensitivity at seed germination
      and seedling stages in rice.
AB  - Abscisic acid (ABA) is one of the important plant hormones, which plays a
      critical role in seed development and adaptation to abiotic stresses. The
      sensitivity of rice (Oryza sativa L.) to exogenous ABA at seed germination and
      seedling stages was investigated in the recombinant inbred line (RIL) population
      derived from a cross between irrigated rice Zhenshan 97 and upland rice IRAT109,
      using relative germination vigor (RGV), relative germination rate (RGR) and leaf
      rolling scores of spraying (LRS) or culturing (LRC) with ABA as sensitivity
      indexes. The phenotypic correlation analysis revealed that only RGV at
      germination stage was positively correlated to ABA sensitivity at seedling stage.
      QTL detection using composite interval mapping (CIM) and mixed linear model was
      conducted to dissect the genetic basis of ABA sensitivity, and the single-locus
      QTLs detected by both methods are in good agreement with each other. Five single
      QTLs and six pairs of epistatic QTLs were detected for ABA sensitivity at
      germination stage. Eight single QTLs and five pairs of epistatic QTLs were
      detected for ABA sensitivity at seedling stage. Two QTLs were common between LRS
      and LRC; and one common QTL was detected for RGV, LRS and LRC simultaneously.
      These results indicated that both single and epistatic loci were involved in the
      ABA sensitivity in rice, and the genetic basis of ABA sensitivity at seed
      germination and seedling stage was largely different.

PMID- 16800385
TI  - Dissection of additive, epistatic effect and Q x E interaction of quantitative
      trait loci influencing stigma exsertion under water stress in rice.
AB  - Four flowering related traits, spikelet number per panicle (SNP), percentage of
      single exserted stigma (PSES), dual exserted stigma (PDES) and total exserted
      stigma (PES) of a RI population with 185 lines under water stress and non-stress
      conditions for 2 years, were investigated in a drought tolerance screening
      facility. ANOVA results showed high significance between years, lines, and water
      stress treatments, together with interactions among them in pairs. Highest
      phenotypic correlation was found between PSES and PES (r = 0.9752***), followed
      by PDES and PES (r = 0.7150***), and PSES and PDES (r = 0.5424***). Based on a
      linkage map of 203 SSR markers, six main effect QTLs were detected for SNP and
      three or four main effect QTLs were associated with PSES, PDES and PES under
      stress or non-stress conditions. There were one to nine pairs of epistatic QTLs
      influencing SNP and stigma exsertion. The contribution rates of additive and
      epistatic effects seemed to be in a low magnitude for most cases (0.76%-9.92%)
      while a few QTLs or QTL pairs explained more than 10% of total variance. Some
      main effect QTL and epistasis were commonly detected among PSES, PDES and PES,
      explaining the high positive correlation between them. Few QTLs were detected
      under both water stress and non-stress condition, implying that drought had
      severe impact on the genetic behaviors of both spikelet number and stigma
      exsertion.

PMID- 16800386
TI  - Identification of quantitative trait loci controlling drought tolerance at
      seedling stage in Chinese Dongxiang common wild rice (Oryza rufipogon Griff.).
AB  - Common wild rice (Oryza rufipogon Griff.) is the ancestor of cultivated rice (O.
      sativa L.), which has a greater genetic diversity and important traits that
      remain to be employed in cultivated rice. In this study, a set of introgression
      lines (BC4F5 and/or BC4F6) carrying various introgressed segments from common
      wild rice, collected from Dongxiang county, Jiangxi Province, China, in the
      background of an Indica (O. sativa L. ssp. indica) cultivar, Guichao 2, was used.
      A total of 12 drought-related quantitative trait loci (QTL) were identified by
      investigating drought tolerance of introgression lines under 30% PEG treatment at
      the young seedlings stage. Of these QTLs, the alleles of 4 QTLs on chromosome 2,
      6 and 12 from Dongxiang common wild rice were responsible for increased drought
      tolerance of the introgression lines. In particular, a QTL qSDT12-2, near RM17 on
      chromosome 12, was consistently detected in different replications, and expressed
      stably under PEG stress throughout the study. It was also found that the QTLs
      located on different chromosomes might express at different stages.

PMID- 16800387
TI  - Genetic analysis and histological study of red seed in rice.
AB  - Reciprocal crosses between red and achromatic rice revealed that the seed color
      of F1 was determined by its female parent. According to the seed color and plant
      segregation ratio of F1, F2, and F3 generations, the red phenotype of red double
      haploid seed was determined by a dominant, monogene with maternal effect.
      Histological study showed that the red pigments accumulated in the pericarp layer
      only. The assay of developmental timing of pigment accumulation showed that the
      red color accumulated from desiccation stage to perfectly maturation stage of the
      seeds.

PMID- 16800388
TI  - Karyotype analysis of Gossypium arboreum x G. bickii by genome in situ
      hybridization.
AB  - By using genome in situ hybridization (GISH) on root somatic chromosomes of
      allotetraploid derived from the cross Gossypium arboreum x G. bickii with genomic
      DNA (gDNA) of G. bickii as a probe, two sets of chromosomes, consisting of 26
      chromosomes each, were easily distinguished from each other by their distinctive
      hybridization signals. GISH analysis directly proved that the hybrid G. arboreum
      x G. bickii is an allotetraploid amphiploid. The karyotype formula of the species
      was 2n = 4x = 52 = 46m (4sat) + 6sm (4sat). We identified four pairs of
      satellites with two pairs in each sub-genome. FISH analysis using 45S rDNA as a
      probe showed that the cross G. arboreum x G. bickii contained 14 NORs. At least
      five pairs of chromosomes in the G sub-genome showed double hybridization (red
      and blue) in their long arms, which indicates that chromatin introgression from
      the A sub-genome had occurred.

PMID- 16800390
TI  - Herpes and HIV infection--has the time come to act?
AB  - It has been known for some years that the ulcerative and inflammatory STIs lead
      to an increased risk of HIV transmission. In particular, there is a two- to four
      fold increased risk of HIV-1 acquisition associated with prevalent herpes simplex
      virus type 2. The challenges are discussed herein.

PMID- 16800389
TI  - Human papillomavirus vaccines: challenges to implementation.
AB  - Clinical trials for prophylactic human papillomavirus (HPV) vaccines have shown
      overwhelmingly positive results. It is expected that with good coverage of the
      vaccine, 70% of cervical cancers will be prevented, as will a proportion of other
      HPV-related anogenital diseases. Issues that will require careful consideration
      will include: whether males and females should be vaccinated; the durability of
      the immune response; the proportion of attributable disease to the HPV types
      targetted by the vaccines; and accessibility and cost of the vaccine. Central to
      an effective vaccination programme will be clear, concise and consistent
      educative messages regarding HPV not only to the lay public, but also the medical
      profession.

PMID- 16800391
TI  - A clinical update on female androgen insufficiency--testosterone testing and
      treatment in women presenting with low sexual desire.
AB  - The diagnosis of female androgen deficiency syndrome is suggested by complaints
      of a diminished sense of well being, persistent unexplained fatigue and decreased
      sexual desire, sexual receptivity and pleasure in a woman who is oestrogen
      replete and in whom no other significant contributing factors can be identified.
      The diagnosis is supported by the finding of low circulating concentrations of
      free testosterone. Barriers to its recognition include the non-specificity of the
      symptoms and methodological problems due to insensitive testosterone assays.
      Barriers to its treatment include the unavailability of satisfactory forms of
      testosterone for administration to women and lack of data regarding long-term
      safety. Although several conditions lead to clear-cut androgen deficiency, such
      as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and
      use of oral contraceptives and oral oestrogens, it is important for clinicians to
      recognise that in normal women, androgen levels decline by 50% from the early 20s
      to the mid 40s, and hence age-related androgen insufficiency may occur in women
      in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements
      of free testosterone requires a sensitive and reliable assay for total
      testosterone, and quantitation of sex hormone binding globulin, from which free
      testosterone is readily calculated. Adverse effects of testosterone treatment are
      few if replacement is monitored to achieve physiological circulating testosterone
      concentrations. Currently, available methods include testosterone implants and
      testosterone creams, and transdermal patches and sprays are in development.

PMID- 16800392
TI  - The role of contact efficacy in evaluating sexual health promotion--evidence
      based outreach work within a public sex environment.
AB  - BACKGROUND: This paper explores the role of contact efficacy in evidence-based
      health promotion by evaluating a public sex environment (PSE) based sexual health
      outreach program. The service operated in situ from a dedicated mobile unit to
      promote sexual health among PSE users. METHODS: A cross-sectional survey
      (response rate 56%) measured socio-demographics, sexual health behaviours and
      outreach-service use among men sampled within the PSE (n = 216). RESULTS: Most
      participants were aware of the service and two-thirds had contacted them. Men who
      had not completed hepatitis A vaccination (odds ratio (OR) = 2.02), who had ever
      received money for sex (OR = 2.07) or who reported a diagnosed mental health
      disorder(s) (OR = 2.38) were significantly more likely to have contacted the
      service. Although 89% of service users perceived the intervention positively,
      only 26% felt it had contributed to sexual behaviour changes. CONCLUSIONS: The
      'mobile-unit' outreach model contacted a large proportion of PSE users,
      specifically men who had greater health needs. We advocate the adoption of this
      outreach model over traditional PSE-based outreach approaches. Contact efficacy
      evaluation is useful to assess ongoing health interventions. However, caution
      must be exerted when interpreting certain contact efficacy results. Since
      causality may not always be inferred, triangulation with other evaluative
      methodologies is recommended.

PMID- 16800393
TI  - Triage in a public outpatient sexual health clinic.
AB  - BACKGROUND: The increasing prevalence of sexually transmissible infections in
      Australia, coupled with a NSW Health Department requirement to target services to
      those most in need, has led many services to investigate patient triage as a way
      of better using scarce resources. In October 1997, a Triage Nurse position was
      trialled that aimed to facilitate the optimal flow of patients through the Sydney
      Sexual Health Centre (SSHC) clinic in an efficient and patient-focussed manner. A
      pre and post implementation time-flow study was conducted to analyse the effect.
      A staff survey was also completed to ascertain staff acceptance of the Nurse
      Triage system. METHODS: A time-flow data survey tool was developed and placed in
      the medical record of every person attending the SSHC in one month in 1997 and
      again in 1999. The staff survey was an 11-item likert scale questionnaire
      administered to all centre staff. Data were analysed and average visit and
      waiting times were generated. RESULTS: When comparing 1997 with 1999 data, the
      main results of note were that the length of consultation had been stable or
      decreased, the average wait time had remained stable or decreased and the wait
      time in the medical and nursing unbooked clinic had decreased. The average wait
      time for the unbooked clinic had decreased from approximately 24 minutes in 1997
      to approximately 12 minutes in 1999. CONCLUSIONS: Since the introduction of Nurse
      Triage, the average overall waiting times for those who attend without an
      appointment has halved and the wait to see a doctor and a nurse has decreased.
      The majority of staff felt that the triage process had improved patient flow.

PMID- 16800394
TI  - Prevalence of genital human papillomavirus DNA in a sample of senior school-aged
      women in the Australian Capital Territory.
AB  - BACKGROUND: A strong association between persistent infection with oncogenic
      types of human papillomavirus (HPV) and cervical cancer is well established.
      Small numbers of international studies examining adolescent HPV infection and the
      risk factors associated are published, but there is currently no evidence on the
      prevalence and risk factors for HPV in an Australian, sexually active female
      adolescent population. METHODS: To provide prevalence and risk factors for HPV in
      a female sexually active, senior high school population in the Australian Capital
      Territory (ACT), a convenience sample of 161, 16-19-year-old females attending a
      senior high school was evaluated. The sample formed part of a larger sample
      recruited for a study of sexually transmitted infections and blood-borne viruses
      in senior high school students. A clinical record was used to collect information
      about sexual and other risk behaviours, while self-collected vaginal swabs were
      tested for HPV DNA detection and genotyping using polymerase chain reaction.
      RESULTS: The prevalence of HPV DNA in this sample overall was 11.2%, with
      multiple genotypes in 38%. No statistically significant associations were found
      between HPV DNA and the number of male partners, age of coitarche, time since
      first sexually active, condom use, smoking or alcohol intake. CONCLUSIONS: This
      is the first Australian study that has examined the prevalence and risk factors
      for genital HPV in this demographic group. The prevalence of HPV infection is
      slightly lower than reported in similar age groups overseas and is lower than
      other Australian studies in older women and those attending sexual health
      centres. Of HPV-positive young women, high-risk genotypes were found in over
      half, with more than one-third of HPV existing as multiple genotypes. Large
      community-based prevalence studies are needed to guide the development of
      recommendations for the vaccination of young women against HPV and to support
      other health promotion initiatives.

PMID- 16800395
TI  - Knowledge and acceptance of human papillomavirus vaccination: perspectives of
      young Australians living in Melbourne, Australia.
AB  - BACKGROUND: This paper explores knowledge of and attitudes toward sexually
      transmissible infections, human papillomavirus (HPV) vaccination and vaccine
      acceptability among young people in Australia. It also explores factors
      influencing acceptance and attempts to identify gender differences in knowledge
      and acceptance. METHODS: The study employed a qualitative approach and involved
      14 in-depth interviews with young men and women aged between 18 and 23 years who
      reside in Melbourne, Australia. RESULTS: The findings suggest that knowledge of
      HPV is inadequate; however, this was not found to have any impact on vaccine
      acceptance, which was reported as high. No clear gender differences were found in
      virus and vaccine knowledge and vaccine acceptance. CONCLUSION: It is clear in
      the present study that vaccination is generally viewed positively by the young
      men and women involved in the study and the health beliefs of these individuals
      have been shaped largely by several factors including cost of the vaccine, access
      to the vaccine and personal susceptibility to the virus.

PMID- 16800396
TI  - Risk factors and causes of death in the Australian HIV Observational Database.
AB  - INTRODUCTION: Mortality rates in HIV-infected people remain high in the era of
      highly active antiretroviral treatment (HAART). The objective of this paper was
      to examine causes of deaths in the Australian HIV Observational Database (AHOD)
      and compare risk factors for HIV-related and HIV-unrelated deaths. METHODS: Data
      from AHOD, an observational study of people with HIV attending medical sites
      between 1999 and 2004, were analysed. Primary and underlying causes of death were
      ascertained by sites completing a standardised cause of death form. Causes of
      death were then coded as HIV-related or HIV-unrelated. Risk factors for HIV
      related and unrelated deaths were assessed using survival analysis among patients
      who had a baseline and at least one follow-up CD4 and RNA measure. RESULTS: The
      AHOD had enrolled 2329 patients between 1999 and 2004. During this time, a total
      of 105 patients died, with a crude mortality rate of 1.58 per 100 person years.
      Forty-two (40%) deaths were HIV-related (directly attributable to an AIDS event),
      55 (52%) HIV-unrelated (all other causes), and eight had unknown cause of death.
      Independent risk factors for HIV-related deaths were low CD4 count and receipt of
      a larger number of antiretroviral treatment combinations. Among HIV-unrelated
      deaths, low CD4 count and older age were independent risk factors. CONCLUSIONS:
      In AHOD in the HAART era, mortality in people with HIV remains around 10-fold
      higher than in the general population. In our analyses, HIV-unrelated deaths were
      associated with more advanced HIV disease in a similar way to HIV-related deaths.

PMID- 16800397
TI  - A clinico-aetiological and ultrasonographic study of Peyronie's disease.
AB  - BACKGROUND: Peyronie's disease is a localised connective tissue disorder that
      involves the tunica albuginea of the penis. Although long recognised as an
      important clinical entity of the male genitalia, the aetiology of this disease
      has remained poorly understood. METHODS: The epidemiology and clinical
      presentation of Peyronie's disease during a 10-year period was evaluated.
      RESULTS: Forty-two men with Peyronie's disease from Chandigarh, India were
      reviewed retrospectively. The prevalence of Peyronie's patients was 1.97/1000
      patients. Their ages ranged from 23 to 70 years. Most of them presented during
      the early phase of the disease. The most common presenting complaint was penile
      curvature in 34 (80.95%) followed by pain on erection in 28 (66.66%). History of
      penile trauma was revealed by four (9.52%) patients. Among the risk factors,
      hypercholesterolemia (60%), hypertension (33.3%) and asymptomatic hyperuricemia
      (28.34%) were the most common. Twenty-two patients with Peyronie's disease were
      studied by ultrasonography. Ultrasonogram was more accurate than clinical
      assessment in delineating the extent of lesions. In one-third of the patients,
      sonography demonstrated the plaques to be more extensive than had been detected
      by clinical examination. CONCLUSIONS: The clinical symptoms and signs in our
      study were, in general, similar to those found in the previous studies. Higher
      incidence of hypertension and diabetes in patients with Peyronie's disease may
      also be to an extent due to patients being in an older age group.

PMID- 16800398
TI  - Genital ulcer disease in central Australia: predictors of testing and outcomes.
AB  - OBJECTIVES: To identify factors associated with the uptake and outcome of testing
      for infectious causes of genital ulcer disease (GUD) in central Australia.
      METHODS: Prospective investigation of GUD cases in central Australia from
      February 2002 to August 2003. Data were collected from primary health care
      clinics in remote indigenous communities of Central Australia. RESULTS: During
      the study period, 134 cases of GUD were reported and investigated. Of these
      cases, 71 (53%) were in women (age range 14-75, median 28) and 63 (47%) in men
      (14-63, median 28). Testing for syphilis was undertaken for 111 (82.8%) cases, 75
      (56%) were tested for herpes simplex virus infection, and 82 (61.2%) for
      donovanosis. Testing for at least one of the three sexually transmissible
      pathogens of interest was undertaken in 128 (95.5%) cases, while 99 (73.9%) were
      tested for two pathogens and 41 (30.6%) for all three agents. Of subjects tested,
      19.8% had new syphilis infection, 51% had herpes simplex virus infection and 7%
      had donovanosis. In 19 of 41 (46.3%) subjects fully investigated no cause for
      genital ulceration was found. CONCLUSION: This study provides the first
      quantitative description of GUD diagnosis in central Australia. Logistic
      constraints limited the systematic application of diagnostic tests. Current
      treatment protocols may need to be reassessed in light of the higher than
      expected detection of genital herpes as a cause of GUD.

PMID- 16800399
TI  - Screening for chlamydia and gonorrhoea in men who have sex with men in clinical
      and non-clinical settings.
AB  - BACKGROUND: There are few published data on the rate of chlamydia and gonorrhoea
      infection in men who have sex with men (MSM). Our aim was to determine the rate
      of positive chlamydia and gonorrhoea tests in this population in the Australian
      Capital Territory (ACT). METHODS: Results of all chlamydia and gonorrhoea tests
      generated by Canberra Sexual Health Centre between June 2001 and September 2003,
      including those from outreach clinics, were reviewed (audit one). Between
      September 2003 and April 2004, Canberra Sexual Health Centre outreach program
      staff and a general practitioner with a high caseload of MSM offered screening of
      the throat, urethra and rectum to all MSM, irrespective of their reported
      participation in unprotected anal intercourse. Chlamydia and gonorrhoea test
      results generated during this period were reviewed (audit two). RESULTS: In the
      first audit, 1086 specimens from 314 individuals were tested and 30/314 (9.6%,
      95% CI 6.6-13.4) men were positive for chlamydia in one or more anatomical site.
      A total of 306 specimens from 118 individuals were tested for gonorrhoea. Of
      these, eight (6.8%, 95% CI 3.0-12.9) individuals tested positive. In the second
      audit, 16 of 157 men (10.2%, 95% CI 9.5-16.0) tested positive for chlamydia and
      4/155 (2.6%, 95% CI 0.7-6.5) tested positive for gonorrhoea. The rectum was the
      most commonly infected anatomical site for both infections. The overall
      proportions of positive chlamydia and gonorrhoea tests were 36/471 (7.6%, 95% CI
      5.4-10.4) and 12/273 (4.4%, 95% CI 2.2-7.6) respectively. CONCLUSIONS: These
      data, collected in a range of settings, indicate high rates of chlamydia and
      gonorrhoea in MSM in the ACT and provide support for annual testing, particularly
      of the rectum, in this population.

PMID- 16800400
TI  - An audit of contact tracing activities and records for chlamydia in an urban
      sexual health clinic.
AB  - The National Sexually Transmissible Infections Strategy 2005-2008 emphasised the
      importance of control of chlamydia and recognised contact tracing as an important
      health tool for this. This paper reports on a recent audit of contact tracing
      conducted at the Gold Coast Sexual Health Clinic.

PMID- 16800401
TI  - QuantiFERON-TB GOLD--An innovation in tuberculosis screening.

PMID- 16800402
TI  - Determinants of employee participation in physical activity: critical review of
      the literature.
AB  - The purpose of this article is to provide a review of research literature related
      to factors that influence employee participation in physical activity. Eleven
      published studies investigating physical activity in samples of adult employees
      were included in this review. Across these studies, self-efficacy, or belief in
      personal ability to perform this health behavior, was the best predictor of
      physical activity among employees. Perceived benefits of physical activity and
      perceived health status were also found to influence participation in physical
      activity. Occupational health nurses could offer self-care classes and
      intervention programs that assist employees in improving their perceptions of
      self-efficacy to perform physical activity. Additionally, occupational health
      nurses should continue to reinforce the benefits of physical activity in all
      health promotion venues.

PMID- 16800403
TI  - Promoting personal safety of building service workers: issues and challenges.
AB  - This exploratory, descriptive study conducted at a large western Canadian
      university solicited perceptions of personal safety among building service
      workers who perform night shift work alone. Ten semi-structured interviews were
      conducted at approximately 10:00 p.m. or 7:00 a.m with a convenience sample of
      night building service workers in private or semi-private locations on the
      university campus. Transcribed interview data were subjected to inductive content
      analysis using descriptive, interpretive, and pattern coding (Miles & Huberman,
      1994). Results suggest that building service night shift workers are exposed to
      personal safety hazards in their physical and psychosocial work environments. In
      addition, culturally and linguistically appropriate delivery of safety training
      and education about policies and procedures is required for culturally diverse
      building service workers. Promotion of personal safety in this heterogeneous
      worker population requires due diligence, assessment, and advocacy.

PMID- 16800404
TI  - Chemical exposures in the workplace: effect on breast cancer risk among women.
AB  - Occupational health nurses need to be aware of the current science on breast
      cancer risks in the workplace because they are risk communicators for employees
      and their families. Occupational health nurses can serve as advocates for
      necessary research ultimately leading to risk reduction and prevention strategies
      in the workplace. Current research suggests exposure to organic solvents, metals,
      acid mists, sterilizing agents (ethylene oxide), some pesticides, light at night
      (shift work), and tobacco smoke increases breast cancer risk among women in
      occupational settings. Animal cancer bioassays conducted by the National
      Toxicology Program indicate more than 40 chemicals can induce mammary tumors, and
      most of these are still in production. A variety of occupations worldwide,
      including health care providers and metal, textile, dye, rubber, and plastic
      manufacturing workers, have been identified as having some evidence of higher
      breast cancer risk. Although some chemical exposures are suspected to affect
      breast cancer risk, estimates of or actual exposures to these chemicals in the
      workplace often have not been determined. Research needed to better identify
      breast cancer risks in occupational settings includes monitoring breast cancer
      incidence in occupations with exposures to suspected carcinogens, characterizing
      chemical exposures by job type and task, determining whether potential gender
      differences affect chemical exposures, and using molecular approaches to identify
      gene-environment interactions.

PMID- 16800405
TI  - The meaning of occupational health among human resources professionals--a
      qualitative study.
AB  - The study findings provide clear rationale for employing occupational health
      nurses as specialists in understanding occupational health, particularly in the
      areas of information seeking (e.g., identifying health resources and best
      practices) and illness or disability management (e.g., managing complex cases and
      addressing psychosocial factors). Occupational health nurses can assist human
      resources professionals to direct their energies to administrative and cultural
      features within their organizations that impact the health of employees and that
      clearly fall within their realm of expertise (e.g., working to create a workplace
      climate of genuine concern for employees). Occupational health nurses can provide
      aggregate information on the health of the work force to strategically encourage,
      direct, and harness employer investments in workplace health. Finding ways to
      translate and communicate workplace health information so it is accessible and
      useable by employers to direct decision making is a key role for occupational
      health nurses.

PMID- 16800406
TI  - Adult learners reframed.

PMID- 16800407
TI  - Perioperative glucose control: how tight is just right for everyone?

PMID- 16800408
TI  - Outpatient management of cirrhosis.

PMID- 16800409
TI  - Negative pressure wound therapy: an important adjunct to wound care.

PMID- 16800410
TI  - Prevalence of peripheral arterial disease in a cohort of diabetic patients.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of peripheral
      diseases in diabetics of different age groups, the role of color Doppler in
      peripheral arterial disease in diabetics, and to compare the prevalence of
      peripheral arterial disease (PAD) in diabetics taking different therapy
      modalities. METHODS: In a hospital-based prospective study conducted over 19
      months, we screened 100 consecutive type 2 diabetic patients and 50 consecutive
      nondiabetic patients matched for demographics and ethnicity. History, physical
      examination and color Doppler results were analyzed. The degree of stenosis in
      PAD was graded according to Jager's criteria. RESULT: The prevalence of PAD was
      8% in controls and 24% in diabetics. There were 60 subjects (60%) greater than 50
      years of age in the diabetic population and 36 (72%) subjects in the nondiabetic
      group. There was male preponderance with 70% of diabetic patients and 60% of
      nondiabetic patients being male. According to mode of therapy, the prevalence of
      PAD was found to be 20% in diabetics taking oral hypoglycemic agents and insulin,
      27.2% on oral hypoglycemic agents, and 25% on insulin therapy. CONCLUSION: This
      study suggests that there is a higher prevalence of PAD in diabetics as compared
      with controls. The prevalence of PAD is directly proportional to the duration of
      diabetes and age of the person. The prevalence of PAD is not a function of
      treatment modality. The stenosis associated with PAD in diabetics is generally
      infrapopliteal.

PMID- 16800411
TI  - Adherence and persistence associated with the pharmacologic treatment of
      osteoporosis in a managed care setting.
AB  - BACKGROUND: The effectiveness of chronic therapies can be compromised by poor
      adherence and persistence. MATERIALS AND METHODS: Investigators identified a
      continuously benefit-eligible cohort of women from a large, geographically
      diverse, national managed care plan who were newly diagnosed and treated for
      osteoporosis with alendronate, risedronate, or raloxifene. Drug utilization
      parameters were evaluated over a 12-month follow-up period for the study
      population. Adherence was assessed using a medication possession ratio calculated
      as total days of therapy for medication dispensed/365 days of study follow-up.
      Persistence was defined as continuous therapy on the same drug for each month
      over the entire study period. Adherence and persistence were also evaluated for
      all three study agents in women > or = 65 years of age. RESULTS: In the study
      cohort (N = 10,566), 12-month adherence/ persistence rates were alendronate
      61%/21%, risedronate 58%/19%, and raloxifene 54%/16%. Rates in women > or = 65
      years were similar to those in the entire study cohort. Weekly bisphosphonate
      users had slightly higher 12-month adherence (63% versus 54%, P < 0.05) and
      persistence (22% versus 19%, P = NS) rates than did daily users, independent of
      agent. CONCLUSION: Chronic oral-dosed osteoporosis therapies are associated with
      poor adherence and persistence, regardless of age or dosing regimen. Drug
      therapies and patient management approaches associated with improved adherence
      and persistence could improve the likelihood of achieving the therapeutic
      benefits observed in rigorously controlled clinical trials.

PMID- 16800412
TI  - Financing and budgeting of community-based family medicine residency programs.
AB  - Using an Internet-based survey for the fiscal year 2003 to 2004, 56 community
      based family medicine residency programs participated in primary research of
      current financing and expenditures. A median of dollar 194,125 was invested in
      training each resident annually. The bulk of funding stemmed from sponsoring
      institution support and clinical care revenues. The majority of programs did not
      receive Title VII funds, state, local, or philanthropic support. Clinical care
      activity continued a historical trend of increases. There were 1,076 patient
      visits per resident full-time equivalent, producing 39.5% of program financing.
      The percentage of visits provided to those with Medicaid was 35.9%. Expenses
      included a calculated malpractice rate of dollar 17,097 per faculty full-time
      equivalent. This effort provides a database available for further expansion, a
      comparison to medical school-based residency programs, analyses for reflection on
      program characteristics, and future comparison of historical trends.

PMID- 16800413
TI  - Perioperative glucose control in the diabetic or nondiabetic patient.
AB  - Patients with diabetes are more likely to undergo surgery than nondiabetics, and
      maintaining glycemic control in subjects with diabetes can be challenging during
      the perioperative period. Surgery in diabetic patients is associated with longer
      hospital stay, higher health care resource utilization, and greater perioperative
      mortality. In addition, several observational and interventional studies have
      indicated that hyperglycemia is associated with adverse clinical outcomes in
      surgical and critically ill patients. This paper reviews the pathophysiology of
      hyperglycemia during trauma and surgical stress and will provide practical
      recommendations for the preoperative, intraoperative, and postoperative care of
      diabetic patients.

PMID- 16800414
TI  - Efficacy and central nervous system impairment of newer-generation prescription
      antihistamines in seasonal allergic rhinitis.
AB  - Allergic rhinitis is a highly prevalent disorder and oral antihistamines are
      often used to manage patient symptoms. Older-generation antihistamines, such as
      diphenhydramine and chlorpheniramine, are effective at relieving the symptoms of
      seasonal allergic rhinitis (SAR); however, they are associated with adverse
      events, including sedation and impairment, at, or above, the recommended dose.
      Newer-generation antihistamines, such as desloratadine, cetirizine and
      fexofenadine, were developed to minimize adverse events. In this article, studies
      examining newer-generation antihistamines in adults and children were reviewed.
      The clinical evidence confirms that desloratadine, cetirizine and fexofenadine
      are effective at managing the symptoms of SAR in adults and children; however,
      cetirizine is more likely to cause sedation. Physician intervention is paramount
      to SAR symptom management. It is essential that appropriate treatment relieves
      SAR symptoms with absent or minimal adverse events. This is particularly
      important for those patients involved in skilled and cognitive activities or
      safety-critical jobs.

PMID- 16800415
TI  - Outpatient management of cirrhosis: a narrative review.
AB  - Cirrhosis is the 12th leading cause of death in the United States. Individuals
      with cirrhosis are at risk for many potential complications. Complications can be
      managed or detected early with proper outpatient management. The most lethal of
      these complications is bleeding esophageal varices. All patients with cirrhosis
      should be screened for the presence of varices and treated when indicated. The
      most common complication seen in these patients is ascites. Ascites can be
      treated with dietary modifications and a diuretic regimen. Other potential
      complications include spontaneous bacterial peritonitis, hepatocellular
      carcinoma, hepatic encephalopathy, hepatorenal syndrome, and hepatopulmonary
      syndrome. The outpatient management of these complications will be discussed in
      this paper, along with the use of vaccinations, educating patients about the
      avoidance of hepatotoxic drugs, and when to refer a patient for liver transplant.

PMID- 16800416
TI  - Invasive aspergillosis with central nervous system dissemination in a presumably
      immunocompetent, non-neutropenic patient: case report and review.
AB  - We present a case of a 45-year-old gentlemen with invasive Aspergillosis who has
      no apparent immune deficiencies. Follow up imaging shows improvement after the
      initiation of therapy. The case is accompanied by a brief discussion over
      invasive aspergillosis.

PMID- 16800417
TI  - Saw palmetto-induced pancreatitis.
AB  - Saw palmetto is a frequently used botanical agent in benign prostatic enlargement
      (BPH). Although it has been reported to cause cholestatic hepatitis and many
      medical conditions, Saw palmetto has not been implicated in acute pancreatitis.
      We report a case of a probable Saw palmetto induced acute hepatitis and
      pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years,
      presented with severe non-radiating epigastric pain associated with nausea and
      vomiting. His only significant comorbidity is BPH for which he intermittently
      took Saw palmetto for about four years. Physical examination revealed normal
      vital signs, tender epigastrium without guarding or rebound tenderness. Cullen
      and Gray Turner signs were negative. Complete blood count and basic metabolic
      profile were normal. Additional laboratory values include a serum amylase: 2,152
      mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT:
      1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic
      resonance cholangiography revealed sludge without stones. A hepatic indole
      diacetic acid scan was negative. Patient responded clinically and biochemically
      to withdrawal of Saw palmetto. Two similar episodes of improvements followed by
      recurrence were noted with discontinuations and reinstitution of Saw Palmetto.
      Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto
      abstinence with reoccurrence on reinstitution strongly favors drug effect.
      "Natural" medicinal preparations are therefore not necessarily safe and the
      importance of detailed medication history (including "supplements") cannot be
      over emphasized.

PMID- 16800418
TI  - Fusarium oxysporum pneumonia in an immunocompetent host.
AB  - A case of symptomatic pulmonary infection caused by Fusarium oxysporum occurred
      in a woman after she had cleaned out bird droppings from a boat house. She was
      also a gardener who had mild, chronic obstructive lung disease, but who had no
      evidence of systemic immunosuppression. She was treated with oral voriconazole
      for four months and had marked clinical improvement and mycological cure. To the
      best of our knowledge, this is the first reported case of isolated pulmonary
      fusariosis in an apparently immunocompetent person. Oral voriconazole therapy was
      effective in this clinical setting.

PMID- 16800419
TI  - A newborn with Beals syndrome.
AB  - We present the case of a newborn with multiple connective tissue abnormalities.
      Careful examination of the infant and a detailed history from his mother
      indicated that they were both affected by Beals syndrome (congenital contractural
      arachnodactyly). A viable-term male infant was delivered to a healthy 30-year
      old. The parents had no known history of familial birth defects. After delivery,
      it was noted that the infant could not extend either elbow past 90 degrees.
      Further examination revealed a crumpled helix of the ear, ulnar deviation of the
      fingers, campylodactyly, and hyperextensible ankles. Further questioning revealed
      that the mother also had hyperflexible wrists and ankles, and several
      dislocations of both patellae in childhood. She never received a diagnosis or
      treatment for her condition. A careful examination of newborn deformities and
      extensive history-taking from the parents can reveal previously unknown genetic
      traits. Thus, initiating early screening and intervention can positively impact a
      child's future.

PMID- 16800420
TI  - Orbital hydatid cyst in childhood: a report of two cases.
AB  - Intraorbital hydatid disease (IHD) is quite rare and represents < 1% of the
      Echinococcus cases. In our current communication, we report two children with
      solitary, primary intraorbital hydatid cysts. Both children presented with
      nontender, nonpulsatile proptosis. Imaging workup, including CT and MRI scans of
      the head and the orbits, revealed a retro-bulbar cyst in both patients. Surgical
      resection was performed by employing a fronto-temporo-orbito-zygomatic (FTOZ)
      approach. Accidental intraoperative rupture occurred in one case with no further
      consequences. Albendazole was postoperatively employed for 12 weeks. Outcome was
      excellent in both cases with complete resolution of their symptoms and complete
      visual recovery. Pertinent literature was reviewed with this opportunity.

PMID- 16800421
TI  - Ceftriaxone-resistant Salmonella septicemia and osteomyelitis in sickle cell
      disease adults.
AB  - The majority of data evaluating Salmonella infections in sickle cell anemia (SCD)
      comes from studies performed in children. We report a SCD adult who presented
      with ceftriaxone-resistant Salmonella bacteremia. After appropriate initial
      therapy, persistent back pain prompted evaluation by magnetic resonance imaging
      of the spine, which revealed osteomyelitis and a psoas abscess. The patient
      responded to percutaneous drainage and antibiotics. This report summarizes some
      of the findings of large SCD studies evaluating Salmonella bacteremia and
      osteomyelitis, focusing on adults. Our case exemplifies the need for antibiotic
      coverage for Salmonella species in adult SCD patients with septicemia. We argue
      that imaging studies looking for osteomyelitis should be done routinely in SCD
      patients with Salmonella bacteremia.

PMID- 16800422
TI  - Management of a circumferential lower extremity degloving injury with the use of
      vacuum-assisted closure.
AB  - A 58-year-old male presented with a large circumferential degloving injury and
      was immediately taken to the operating room for further assessment of his wound.
      At that time, a plastic surgeon was consulted to manage the wound due to its size
      and significant soft tissue loss. The decision was made to manage the patient's
      wound with the vacuum-assisted closure (VAC) device to prepare the wound bed for
      grafting. After three weeks of VAC therapy, the wound bed was revascularized with
      granulation tissue and was ready for grafting. The patient underwent a successful
      split thickness skin graft on hospital Day 23 and was discharged home. Follow-up
      visits revealed no scar contracture or functional limitations.

PMID- 16800423
TI  - Concomitant nephrotic syndrome with antinuclear antibody seropositivity and
      Hashimoto thyroiditis in a patient with mycosis fungoides.

PMID- 16800424
TI  - Aspartame-induced Sjogren syndrome.

PMID- 16800425
TI  - CT scans and appendicitis.

PMID- 16800426
TI  - A case of acute hepatitis due to brucellosis.

PMID- 16800427
TI  - Patient's page.

PMID- 16800428
TI  - Revolutions in the care of diabetes with the help of dogs and lizards.

PMID- 16800429
TI  - Chaplains, the hidden assets.

PMID- 16800430
TI  - Ministering to patient and person.

PMID- 16800431
TI  - A physician CEO looks at Clinical Pastoral Education.

PMID- 16800432
TI  - The use of spirituality in alcohol recovery.

PMID- 16800433
TI  - A prevalence study of faith-based healing in the rural southeastern United
      States.
AB  - BACKGROUND: Although prayer and other spiritual practices are common among
      residents of the rural south, the use of faith-based healers (FBH), or healers
      who use prayer as their primary healing modality, has not been explored in this
      population. METHODS: Secondary data analysis from a random digit dialing
      telephone survey of rural adults in eight southern states. RESULTS: Our overall
      response rate was 51% and 193 subjects (4.1%) had seen an FBH practitioner within
      the previous year. FBH use was significantly more common among younger
      respondents (OR 7.21, 95% Ci 2.00, 25.94), women (OR 1.49, 95% CI 1.03, 2.14),
      those reporting poorer health (OR 1.83, 95% CI 1.19, 2.83), and those who
      believed in avoiding physicians (OR 1.82, 95% CI 1.24, 2.67). A relationship
      between FBH use and delayed or foregone medical care, and cost as a barrier to
      obtaining care was not statistically significant after controlling for other
      factors. CONCLUSIONS: Prevalence of FBH use is low, but is significantly related
      to younger age, female gender, poorer health status, barriers to medical care and
      devaluing medical care. Clinicians may consider exploring FBH usage with their
      younger, female patients, and those in poorer health. Policy makers should
      consider how FBH usage is related to various indicators of health care services
      demand, utilization and access.

PMID- 16800435
TI  - Interacting with patients of a different faith: the personal reflection of a
      Buddhist chaplain.

PMID- 16800434
TI  - Alcohol recovery and spirituality: strangers, friends, or partners?
AB  - Alcoholics Anonymous, with its steady but nonspecific promotion of belief in a
      higher power and its emphasis on the group process, long held a near-monopoly in
      the outpatient alcohol recovery field, but its hegemony has now been challenged
      by two very different perspectives. The first is a nonspiritual approach that
      emphasizes the individual's capability to find a personal pathway to sobriety,
      exemplified by Rational Recovery. The second is a faith-based method, built on a
      religious understanding of alcoholism, of which Celebrate Recovery is a prominent
      example, based upon Christianity. Most communities offer a variety of approaches,
      so clinicians who are aware of these differences are in a good position to help
      patients make intelligent choices among the competing recovery philosophies.

PMID- 16800436
TI  - Setting common standards for professional chaplains in an age of diversity.

PMID- 16800437
TI  - Best practices in professional pastoral care.

PMID- 16800438
TI  - What training should be required as an education standard for healthcare and
      hospital chaplains?
AB  - This document discusses training for hospital and healthcare chaplains in the
      light of different UK standards applied by various interested parties. It
      considers the different standards and concludes that there is no single applied
      standard for training for National Health Service (NHS) hospital chaplains across
      the UK. Those models that do exist take differing approaches, with some basing
      their systems on normatively defined views of what a chaplain needs to be
      effective on functional (NHS managerial) or interpersonal (clinical pastoral)
      levels, while others take a more hybrid approach blending these approaches with
      doctrinal concerns. Equally, there is wide variation across different
      denominations and employers. This document seeks to identify where there is
      common ground on domains of competence for chaplaincy training and suggest some
      progress for training which fits into NHS structures and systems.

PMID- 16800439
TI  - Chaplaincy in Europe.
AB  - Chaplaincy is organized in Europe in various ways, depending on the cultural,
      religious, social and governmental aspects which shape healthcare. One of the
      uniting forces in bringing national chaplaincies together into one united body
      has been the European Network of Health Care Chaplaincy (ENHCC). Chaplaincy in
      Europe faces two major difficulties: 1) the professional status of the chaplain
      within the healthcare community; 2) preserving the patient's rights for spiritual
      care. These difficulties are described and note is given to how the ENHCC is
      dealing with them. Finally, special attention is given to how chaplaincy in
      Europe and the medical community interact and what is needed to bridge the gap
      between the two worlds of science and faith.

PMID- 16800440
TI  - The development, status, and future of healthcare chaplaincy.
AB  - This review article provides insight into the evolution of professional
      healthcare chaplaincy. It identifies key historical developments identifying the
      training, qualifications, and competencies of chaplains. Consideration is given
      to both the unique character of the pastoral role in healthcare as well as the
      contribution of chaplains to the interdisciplinary care of patients and families.
      The article points to the emerging need for chaplains to pursue research within
      the clinical context.

PMID- 16800441
TI  - Eye on religion: understanding the cultural/ religious melange in treating
      Chinese patients.

PMID- 16800442
TI  - Eye on religion: confucianism, autonomy and patient care.

PMID- 16800443
TI  - Eye on religion: cultural signs and caring for Chinese patients.

PMID- 16800444
TI  - Controversies in medical ethics: training in abortion.

PMID- 16800445
TI  - Selected annotated bibliography.

PMID- 16800446
TI  - The law and foreseeability.

PMID- 16800447
TI  - Forensic handwriting comparison and other aspects of document examination.

PMID- 16800448
TI  - Complementary/Alternative medicine: medico-legal issues.

PMID- 16800449
TI  - Periodical payments--the development of a pragmatic approach.

PMID- 16800450
TI  - Negligence by the general practitioner.

PMID- 16800451
TI  - Ordered patterning of nanometric rings of single molecule magnets on polymers by
      lithographic control of demixing.
AB  - We report a new patterning process which takes place as a result of demixing of a
      binary polymer/solute mixture. An efficient, sustainable approach for ordering
      nanosized rings of so-called single molecule magnets (SMMs) is thus provided. It
      exploits the self-organization process in which SMM patterned film evolves to a
      spatially correlated pattern of nanosized rings. At long time, the anisotropic
      patterning of the film drives the ring to coalesce, into parallel lines of
      nanometric width.

PMID- 16800452
TI  - Chiroptical activity of BINAP-stabilized undecagold clusters.
AB  - Undecagold cluster compounds [Au11(BINAP)4X2]+ (X = Cl and Br) were synthesized
      by chemical reduction of the corresponding precursor complexes, Au2X2(BINAP),
      where BINAP represents the bidentate phosphine ligand 2,2'-bis(diphenylphosphino)
      1,1'-binaphthyl. The circular dichroism spectra of Au11 stabilized by the
      enantiomers [Au11(R-BINAP)4X2]+ and [Au11(S-BINAP)4X2]+ exhibited intense and
      mirror-image Cotton effect, whereas those of Au11(3+) clusters stabilized by
      achiral monodentate phosphine ligands did not. The origin of the chiroptical
      activity of [Au11(BINAP)4X2]+ is discussed in the context of the structural
      deformation of the Au11(3+) core.

PMID- 16800453
TI  - Tuning the cooperativity of the helix-coil transition by aqueous reverse
      micelles.
AB  - We show in this letter that the thermodynamic properties of helical peptides can
      be tuned by varying the degrees of backbone hydration. The latter was achieved by
      solubilizing peptides in the water pool of sodium bis(2-ethylhexyl)
      sulfosuccinate (AOT) reverse micelles with different water contents or w0 values.
      Far-UV circular dichroism measurements on a series of alanine-rich peptides
      indicate that the helicity of shorter peptides is significantly increased in AOT
      reverse micelles at low w0 values, as compared to the corresponding helical
      content in buffer. This result therefore corroborates the previous simulation
      studies suggesting that desolvation of backbone CO and NH groups increases the
      stability of monomeric helices. In addition, it was found that the thermal
      unfolding transition of these peptides can either be very noncooperative or very
      cooperative, depending on w0 and peptide chain length. A simple model, which
      considers the heterogeneous distribution of the water molecules inside the polar
      core of AOT reverse micelles as well as the geometric confinement effect exerted
      on the peptide by the reverse micelles, was used to interpret these results.

PMID- 16800454
TI  - Understanding the structural properties of a dendrimeric material directly from
      powder X-ray diffraction data.
AB  - Complete structure determination of an early-generation dendrimeric material has
      been carried out directly from powder X-ray diffraction data, using the direct
      space genetic algorithm technique for structure solution followed by Rietveld
      refinement. This work represents the first application of modern direct-space
      techniques for structure determination from powder X-ray diffraction data in the
      case of a dendrimeric material and paves the way for the future application of
      this approach to enable complete structure determination of other dendrimeric
      materials that cannot be prepared as single crystal samples suitable for single
      crystal X-ray diffraction studies.

PMID- 16800455
TI  - Cutting of single-walled carbon nanotubes by ozonolysis.
AB  - Cutting of single-walled carbon nanotubes (SWNT) has been achieved by extensive
      ozonolysis at room temperature. Perfluoropolyether (PFPE) was selected as a
      medium for cutting SWNT due to its high solubility for ozone (O3). A mixture of 9
      wt % of O3 in O2 was bubbled through a homogeneous suspension of pristine SWNT in
      PFPE, at room temperature. The intense disorder mode in the Raman spectra of
      ozonated SWNT indicates that extensive reaction with the sidewalls of SWNT occurs
      during ozonolysis. Atomic force microscopy (AFM) images of SWNT, before and after
      ozonolysis, provided a measure of the extent of the cutting effects. Monitoring
      of the evolved gases for both pristine and purified SWNT indicates CO2 was
      produced during the ozonolysis process with a dependence on both system pressure
      and temperature. During heating, FTIR analysis of gases released indicated that
      carbon oxygen groups on the sidewalls of SWNT are released as CO2. SWNT was found
      to be extensively cut after an ozone treatment with a yield of approximately 80%
      of the original carbon.

PMID- 16800456
TI  - Low temperature kinetics and energetics of the electron and hole traps in
      irradiated TiO2 nanoparticles as revealed by EPR spectroscopy.
AB  - We have monitored exclusively the dynamics of photogenerated charge carriers
      trapping in deep traps and trapped electron-hole recombination in UV irradiated
      anatase TiO2 powders by electron paramagnetic resonance (EPR) spectroscopy at 10
      K. The results reveal that the strategy of using low temperatures contributes to
      the stabilization of the charged pair states for hours by reducing the rate of
      electron-hole recombination processes. Since only the localized states such as
      holes trapped at oxygen anions and electrons trapped at coordinatively
      unsaturated cations are accessible to EPR spectroscopy, the time-dependent
      population and depopulation of these EPR signals reflect the kinetics and
      energetics of these trap states. The data support a model of sequential
      accumulation of deep trap site populations in which the initial fast direct
      trapping into a deep trap site is followed by slower carrier trap-to-trap hopping
      until a deep trap is encountered for both photogenerated electrons and holes.
      Effective modeling of the subsequent decay of trapped-holes is achieved by
      employing a first-order kinetics, whereas the decay of either surface- or inner
      trapped electrons has both a fast and a slow component. The fast component is
      attributed to a trapped-electron and a free-hole recombination, and the slow
      component is attributed to trapped electron-hole recombination. The activation
      energies for the process of diffusion of trapped electrons from their Ti3+
      trapping sites are estimated.

PMID- 16800457
TI  - Structure of electrorheological fluids under an electric field and a shear flow:
      experiment and computer simulation.
AB  - It is known that macroscopic properties of colloidal suspensions are often
      determined by the microstructure of the particles in the suspensions, depending
      on the interparticle, Brownian, and hydrodynamic (if any) forces. We take
      electrorheological (ER) fluids as an example. By using a computer simulation and
      an experimental approach, we investigate the structure of ER fluids subjected to
      both an electric field and a shear flow. The microstructure evolution from random
      structure, to chains, and then to stable lamellar patterns, observed in the
      experiments, agrees very well with that obtained in the simulations. It is shown
      that the formation of such lamellar patterns originates from the difference
      between the dipole moment induced in the particles suspended in the ER fluids
      without shear and the one with shear. The results on the relaxation process of
      structural formation and the internal structure of layers are also presented.
      Thus, it seems possible to achieve various structures and hence desired
      macroscopic properties of colloidal suspensions by adjusting external fields and,
      simultaneously, a shear flow.

PMID- 16800458
TI  - Magnetic core-shell Fe3O4@Ag nanoparticles coated carbon paste interface for
      studies of carcinoembryonic antigen in clinical immunoassay.
AB  - This study demonstrates a novel approach toward development of advanced
      immunosensors based on chemically functionalized core-shell Fe3O4@Ag magnetic
      nanoparticles, and the preparation, characterization, and measurement of relevant
      properties of the immunosensor useful for the detection of carcinoembryonic
      antigen (CEA) in clinical immunoassay. The immunosensor based on the combination
      of a magnetic nanocore and an Ag metallic shell shows good adsorption properties
      for the attachment of the CEA antibody selective to CEA. The core-shell
      nanostructure presents good magnetic properties to facilitate and modulate the
      way it was integrated into a carbon paste. Under optimal conditions, the
      resulting composite presents good electrochemical response for the detection of
      CEA, and allows detection of CEA at a concentration as low as 0.5 ng.mL(-1).
      Importantly, the proposed methodology could be extended to the detection of other
      antigens or biocompounds.

PMID- 16800459
TI  - Probing the 3d spin momentum with X-ray emission spectroscopy: the case of
      molecular-spin transitions.
AB  - We report X-ray emission spectra of Fe(III), Fe(II), and Co(II) spin-crossover
      compounds in their high-spin and low-spin forms. It is shown that all X-ray
      emission features are sensitive to the spin state. Variations of the Kbeta and
      the Kalpha emission line shapes, which are in agreement with theory, can be used
      as quantitative probes of the spin state; it is suggested that with appropriate
      reference experiments one can extract the spin momentum for a general case.
      Resonant X-ray emission spectra unveil details of the redistribution of electrons
      on the 3d levels associated with the spin-state change by revealing features at
      the X-ray absorption preedge not accessible through standard absorption
      measurements.

PMID- 16800460
TI  - The local environment of Cu+ in Cu-Y zeolite and its relationship to the
      synthesis of dimethyl carbonate.
AB  - Cu-exchanged Y zeolite was investigated in order to determine the location of the
      copper cations relative to the zeolite framework and to determine which Cu
      cations are active for the oxidative carbonylation of methanol to dimethyl
      carbonate (DMC). Cu-Y zeolite was prepared by vapor-phase exchange of H-Y with
      CuCl. The oxidation state, local coordination, and bond distances of Al and Cu
      were determined using Al K-edge and Cu K-edge X-ray absorption spectroscopy
      (XAS). Complimentary information was obtained by H2 temperature-programmed
      reduction and by in-situ infrared spectroscopy. Cu-Y has a Cu/Al ratio of unity
      and very little occluded CuCl. The average Al-O and Al-Cu bond distances are 1.67
      angstroms and 2.79 angstroms, respectively, and the average Cu-O and Cu-Si(Al)
      bond distances are 1.99 angstroms and 3.13 angstroms, respectively. All of the Cu
      exchanged is present as Cu+ in sites I', II, and III'. Cu-Y is active for the
      oxidative carbonylation of methanol, and at low reactant contact time produces
      DMC as the primary product. With increasing reactant contact time, DMC formation
      decreases in preference to the formation of dimethoxy methane (DMM) and
      methylformate (MF). The formation of DMM and MF is attributed to the
      hydrogenation of DMC and the hydrogenolysis of DMM, respectively. Observation of
      the catalyst under reaction conditions reveals that most of the copper cations
      remain as Cu+, but some oxidation of Cu+ to Cu2+ does occur. It is also concluded
      that only those copper cations present in site II and III' positions are
      accessible to the reactants, and hence are catalytically active. The dominant
      adsorbed species on the surface are methoxy groups, and adsorbed CO is present as
      a minority species. The relationship of these observations to the kinetics of DMC
      synthesis is discussed.

PMID- 16800461
TI  - An in situ Al K-edge XAS investigation of the local environment of H+- and Cu+
      exchanged USY and ZSM-5 zeolites.
AB  - Aluminum coordination in the framework of USY and ZSM-5 zeolites containing
      charge-compensating cations (NH4+, H+, or Cu+) was investigated by Al K-edge
      EXAFS and XANES. This work was performed using a newly developed in-situ cell
      designed especially for acquiring soft X-ray absorption data. Both tetrahedrally
      and octahedrally coordinated Al were observed for hydrated H-USY and H-ZSM-5, in
      good agreement with 27Al NMR analyses. Upon dehydration, water desorbed from the
      zeolite, and octahedrally coordinated Al was converted progressively to
      tetrahedrally coordinated Al. These observations confirmed the hypothesis that
      the interaction of water with Bronsted acid protons can lead to octahedral
      coordination of Al without loss of Al from the zeolite lattice. When H+ is
      replaced with NH4+ or Cu+, charge compensating species that absorb less water,
      less octahedrally coordinated Al was observed. Analysis of Al K-edge EXAFS data
      indicates that the Al-O bond distance for tetrahedrally coordinated Al in
      dehydrated USY and ZSM-5 is 1.67 angstroms. Simulation of k3chi(k) for Cu+
      exchanged ZSM-5 leads to an estimated distance between Cu+ and framework Al atoms
      of 2.79 angstroms.

PMID- 16800462
TI  - Electronic structure and photocatalytic characterization of a novel photocatalyst
      AgAlO2.
AB  - A novel photocatalyst, AgAlO2, was prepared by cation exchange reaction and
      characterized by powder X-ray diffraction. The result showed AgAlO2 crystallizes
      in the layered orthorhombic structure with space group was Pna2(1). The energy
      band and electronic structures of AgAlO2 were calculated based on the crystal
      structure. It was found that AgAlO2 is an indirect band gap semiconductor. The
      valence band top mainly consists of O-2p orbitals and Ag-4d orbitals and the
      conduction band bottom is mainly constructed of Ag-5s5p orbitals. The band gap of
      AgAlO2 was estimated to be about 2.8(1) eV with UV-vis diffuse reflectance
      spectrometry. The photocatalytic activity of AgAlO2 was characterized by
      photocatalytically decomposing the dye alizarin red (AR) under visible light
      irradiation, and AR could be decomposed about 70% under 2 h of visible light
      irradiation.

PMID- 16800463
TI  - Comparative photophysical properties of free-base, bis-Zn(II), bis-Cu(II), and
      bis-Co(II) doubly N-confused hexaphyrins(1.1.1.1.1.1).
AB  - We have comparatively investigated the photophysics of a series of bis-metal
      doubly N-confused hexaphyrins(1.1.1.1.1.1) using time-resolved fluorescence,
      femtosecond transient absorption, two-photon absorption measurements, and
      geometry-optimized ab initio calculations. Bis-Zn(II) and free-base doubly N
      confused hexaphyrins exhibit well-resolved and red-shifted B- and Q-like
      absorption bands compared with porphyrins. Their allowed transitions are (pi,pi)
      transitions of the hexaphyrin ring, as confirmed by the HOMO and LUMO frontier
      orbitals based on ab initio calculations at the B3LYP/6-31G level. On the other
      hand, the absorption spectra of bis-Cu(II) and bis-Co(II) doubly N-confused
      hexaphyrins are relatively broad, presumably due to large couplings between the
      metal d-orbitals and pi-electrons of the hexaphyrin ring. Owing to these
      couplings, bis-Cu(II) and bis-Co(II) doubly N-confused hexaphyrins have much
      shorter excited-state lifetimes of 9.4 +/- 0.3 ps and 670 fs, respectively, than
      those (267 +/- 16 and 62.4 +/- 1.2 ps, respectively) of bis-Zn(II) and free-base
      doubly N-confused hexaphyrins. The two-photon absorption cross section (sigma(2))
      values, which are believed to depend strongly on the ring planarity (pi
      conjugation), are in line with the excited-state lifetime trends.

PMID- 16800464
TI  - Photoluminescence and Raman scattering from catalytically grown Zn(x)Cd(1-x)Se
      alloy nanowires.
AB  - Zn(x)Cd(1-x)Se alloy nanowires, with composition x = 0, 0.2, 0.5, 0.7, and 1,
      have been successfully synthesized by a chemical vapor deposition (CVD) method
      assisted with laser ablation. The as-synthesized alloy nanowires, 60-150 nm in
      diameter and several tens of micrometers in length, complied with a typical vapor
      liquid-solid (VLS) growth mechanism. The Zn(x)Cd(1-x)Se nanowires are single
      crystalline revealed from high-resolution transmission electron microscopic
      (HRTEM) images, selected area electron diffraction (SAED) patterns, and X-ray
      diffraction (XRD) measurement. Compositions of the alloy nanowires can be
      adjusted by varying the precursor ratios of the laser ablated target and the CVD
      deposition temperature. Crystalline structures of the Zn(x)Cd(1-x)Se nanowires
      are hexagonal wurtzite at x = 0, 0.2, and 0.5 with the [0 1 -1 0] growth
      direction and zinc blende at x = 0.7 and 1 with the [1 -1 1] growth direction.
      Energy gaps of the Zn(x)Cd(1-x)Se nanowires, determined from micro
      photoluminescence (PL) measurements, change nonlinearly as a quadratic function
      of x with a bowing parameter of approximately 0.45 eV. Strong PL from the
      Zn(x)Cd(1-x)Se nanowires can be tuned from red (712 nm) to blue (463 nm) with x
      varying from 0 to 1 and has demonstrated that the alloy nanowires have potential
      applications in optical and sensory nanotechnology. Micro-Raman shifts of the
      longitudinal optical (LO) phonon mode observed in the Zn(x)Cd(1-x)Se nanowires
      show a one-mode behavior pattern following the prediction of a modified random
      element isodisplacement (MREI) model.

PMID- 16800465
TI  - Mg-based nanocomposites with high capacity and fast kinetics for hydrogen
      storage.
AB  - Magnesium and its alloys have shown a great potential in effective hydrogen
      storage due to their advantages of high volumetric/gravimetric hydrogen storage
      capacity and low cost. However, the use of these materials in fuel cells for
      automotive applications at the present time is limited by high hydrogenation
      temperature and sluggish sorption kinetics. This paper presents the recent
      results of design and development of magnesium-based nanocomposites demonstrating
      the catalytic effects of carbon nanotubes and transition metals on hydrogen
      adsorption in these materials. The results are promising for the application of
      magnesium materials for hydrogen storage, with significantly reduced absorption
      temperatures and enhanced ab/desorption kinetics. High level Density Functional
      Theory calculations support the analysis of the hydrogenation mechanisms by
      revealing the detailed atomic and molecular interactions that underpin the
      catalytic roles of incorporated carbon and titanium, providing clear guidance for
      further design and development of such materials with better hydrogen storage
      properties.

PMID- 16800466
TI  - Architectural control syntheses of CdS and CdSe nanoflowers, branched nanowires,
      and nanotrees via a solvothermal approach in a mixed solution and their
      photocatalytic property.
AB  - Wurtzite CdS and CdSe nanostructures with complex morphologies such as urchin
      like CdS nanoflowers, branched nanowires, and fractal nanotrees can be produced
      via a facile solvothermal approach in a mixed solution made of diethylenetriamine
      (DETA) and deionized water (DIW). The morphologies of CdS and CdSe nanocrystals
      can be easily controlled via tuning the volume ratio of DETA and DIW. Urchin-like
      CdS nanoflowers made of CdS nanorods are in a form of highly ordered hierarchical
      structures, while the nanowires are branched nanowires, and the fractal CdS
      nanotrees are a buildup of branched nanopines. The results demonstrated that
      solvothermal reaction in a mixed amine/water can access a variety of complex
      morphologies of semiconductor materials. The photocatalytic activity of CdS
      particles with different morphologies has been tested by the degradation of acid
      fuchsine under both UV and visible light, showing that the as-prepared branched
      CdS nanowires exhibit high photocatalytic activity for degradation of acid
      fuchsine.

PMID- 16800467
TI  - Synthesis of copper-core/carbon-sheath nanocables by a surfactant-assisted
      hydrothermal reduction/carbonization process.
AB  - A simple hydrothermal method has been developed for the one-step synthesis of
      copper-core/carbon-sheath nanocables in solution. The obtained nanostructures
      were characterized by X-ray diffraction (XRD), transmission electron microscopy
      (TEM), and high-resolution TEM (HRTEM), Raman, and UV-vis spectrum analysis.
      These copper@carbon nanocables formed through the hydrothermal
      reduction/carbonization in the presence of surfactant cetyltrimethylammonium
      bromide (CTAB) acting as the structure-directing agent by hydrothermal treatment.
      HRTEM and selected-area electron diffraction (SAED) indicate that the resulted Cu
      nanowires had the preferred [110] growth direction. The influence of the reaction
      temperature, reaction time, and pH on the final products was investigated in
      detail. The possible formation mechanism for copper-core/carbon-sheath nanocables
      was also proposed. Amorphous carbon nanotubes can be obtained by etching the
      copper core in the nanocables.

PMID- 16800468
TI  - Molecular dynamics study to identify the reactive sites of a liquid squalane
      surface.
AB  - Molecular dynamics simulations of liquid squalane, C30H62, were performed,
      focusing in particular on the liquid-vacuum interface. These theoretical studies
      were aimed at identifying potentially reactive sites on the surface, knowledge of
      which is important for a number of inelastic and reactive scattering experiments.
      A united atom force field (Martin, M. G.; Siepmann, J. I. J. Phys. Chem. B 1999,
      103, 4508-4517) was used, and the simulations were analyzed with respect to their
      interfacial properties. A modest but clearly identifiable preference for methyl
      groups to protrude into the vacuum has been found at lower temperatures. This
      effect decreases when going to higher temperatures. Additional simulations
      tracking the flight paths of projectiles directed at a number of randomly chosen
      surfaces extracted from the molecular dynamics simulations were performed. The
      geometrical parameters for these calculations were chosen to imitate a typical
      abstraction reaction, such as the reaction between ground-state oxygen atoms and
      hydrocarbons. Despite the preference for methyl groups to protrude further into
      the vacuum, Monte Carlo tracking simulations suggest, on geometric grounds, that
      primary and secondary hydrogen atoms are roughly equally likely to react with
      incoming gas-phase atoms. These geometric simulations also indicate that a
      substantial fraction of the scattered products is likely to undergo at least one
      secondary collision with hydrocarbon side chains. These results help to interpret
      the outcome of previous measurements of the internal and external energy
      distribution of the gas-phase OH products of the interfacial reaction between
      oxygen atoms and liquid squalane.

PMID- 16800469
TI  - What is the role of the complexant in the large first hyperpolarizability of
      sodide systems Li(NH3)(n)Na (n = 1-4)?
AB  - To explore the coordination number (around the cation) dependence of the
      nonlinear optical (NLO) properties in alkalides, this paper studies the
      structures and large NLO responses of model alkalides, Li(NH3)(n)Na (n = 1-4). At
      the MP2/aug-cc-pVDZ level, the structural characteristic is determined to be that
      the Li-Na distance increases (from 3.030 to 4.646 angstroms) with the increasing
      of the number of NH3 (n from 1 to 4). Results show that Li(NH3)(n)Na (n = 1-4)
      have considerably large first hyperpolarizabilities (beta0). Especially, a
      prominent coordination number dependence of the beta0 value is found as follows:
      beta0 = 13 669 (n = 1) < 26,840 (n = 2) < 39 764 (n = 3) < 77 921 au (n = 4) at
      the MP2 level. With the same coordination number (four N atoms) of Li+ cations,
      the beta0 value (77,921 au) of this "small" inorganic molecule Li(NH3)(n)Na is
      over five times larger than that of the "big" organic molecule Li@Calix[4]pyrrole
      Na (14,772 au). This indicates that the beta0 value is strongly related to the
      flexibility of the complexant. Obviously, the flexibility of (NH3)4 is much
      greater than that of the cup-like shaped Calix[4]pyrrole. This work suggests that
      two important factors should be taken into account to enhance the first
      hyperpolarizability of alkalide, i.e., the coordination number around the cation
      and the flexibility of the complexant.

PMID- 16800470
TI  - Dynamics of photoinduced electron transfer in a molecular donor-acceptor quartet.
AB  - The electronic structures and dynamics of photoinduced charge separation and
      recombination in a new donor/acceptor quartet molecule with bis-oligothiophene
      (BOTH) and bis-perylenediimide (BPDI) blocks attached to a benzene ring were
      described. Detailed transient spectroscopic studies were carried out on this
      compound and reference compounds at isolated molecular levels in solution. Two
      different dynamics of charge separation and recombination associated with two
      types of donor/acceptor pair conformations in solution were observed. These
      results were discussed based on Marcus theory and ascribed to both through-bond
      and through-space electron-transfer processes associated with two different
      orientations of the acceptors relative to the donor group. This molecular system
      exhibits a more efficient charge separation than charge recombination processes
      in both polar and nonpolar organic solvents, indicating that the material is an
      interesting candidate for photovoltaic studies in solid state.

PMID- 16800471
TI  - Energy migration study of random immobile anthracene derivatives by time-resolved
      fluorescence anisotropy decays.
AB  - We describe time-resolved fluorescence anisotropy measurements for a simple 2
      substituted anthracene derivative (2-An-M) as a function of concentration in
      poly(methyl methacrylate) (PMMA) films. The anisotropy decays via energy
      migration among 2-An-M molecules in the matrix. The data were interpreted in
      terms of the survival probability of the initially excited chromophores and are
      in good agreement with the plot predicted using R0 = 1.8 nm, the value of the
      Forster radius determined independently by the spectral overlap method. For all
      concentrations, we found r0 = 0.20 +/- 0.01 for the initial anisotropy at time
      zero, whereas the residual anisotropy, r(infinity), was concentration-dependent
      and higher in magnitude than the theoretically predicted value, 4% of r0. The
      higher residual anisotropy values may originate from the possibility that not all
      of the anthracene molecules are involved in the energy migration process. Similar
      anthracene anisotropy experiments were performed on anthracene-labeled
      poly(isoprene-b-methyl methacrylate) (PI-PMMA). The results show an increased
      depolarization rate for samples containing a higher fraction of polymers labeled
      at the junction with anthracene chromophores.

PMID- 16800472
TI  - Influence of aluminum doping on ferrihydrite nanoparticle reactivity.
AB  - The composition of natural ferrihydrite varies considerably, especially in terms
      of aluminum and silicon substitution. This work examines the influence of
      aluminum content on the redox reactivity of ferrihydrite nanoparticles as
      determined by kinetic studies of the reductive dissolution of the particles by
      hydroquinone. Transition state theory applied to variable-temperature experiments
      is used to measure the activation enthalpy and entropy. The presence of small
      amounts of aluminum (0-2.1 mol % substitution) causes a decrease in deltaH++ and
      an increase in deltaS++, resulting in an overall increase in reactivity.

PMID- 16800473
TI  - Mechanism of laser-induced size-reduction of gold nanoparticles as studied by
      nanosecond transient absorption spectroscopy.
AB  - Gold nanoparticles with an average diameter of approximately 8 nm (Au
      approximately 15,000) were irradiated with a tightly focused pulse laser at 355
      nm in an aqueous solution of sodium dodecyl sulfate (SDS). Transient absorption
      spectra of the solution were measured at 25-100 ns after the laser irradiation.
      The observed transient absorption around 720 nm is assignable to the 2p <-- 1s
      transition of solvated electrons produced via multiple ionization of the gold
      nanoparticles. The nascent charge state of the gold nanoparticles was estimated
      from the transient absorbance. The dependence of the charge state on the SDS
      concentration shows a gradual increase from approximately +60 to approximately
      +70 in the 2 x 10(-4) to 3 x 10(-4) M range and an abrupt increase up to
      approximately +710 at the critical micelle concentration (CMC) of SDS, 8 x 10(-3)
      M. TEM measurements after laser irradiation reveal that the gold nanoparticles
      fragment into Au(approximately 1000) at a SDS concentration of 3 x 10(-4) M,
      whereas they are significantly dissociated into Au(approximately 100) above the
      CMC. The observed correlation between the nascent charge states and the extent of
      size reduction of the gold nanoparticles after the laser treatment indicates that
      the size reduction is caused by the Coulomb explosion of the highly charged gold
      nanoparticles. The mechanism of laser-induced size reduction is quantitatively
      discussed based on the liquid drop model.

PMID- 16800474
TI  - A conclusive demonstration of vibrational pumping under surface enhanced Raman
      scattering conditions.
AB  - We provide a conclusive demonstration of vibrational pumping under Surface
      Enhanced Raman Scattering (SERS) conditions by performing anti-Stokes/Stokes
      ratio measurements over a large spatial area and low power density, down to 10 K
      with dried silver colloids, the dye rhodamine 6G, and 676 nm laser excitation.
      The method we propose allows for the measurement of the cross sections for
      different modes and also provides the determination of the asymmetry between the
      anti-Stokes and Stokes SERS cross sections for each mode.

PMID- 16800475
TI  - Synthesis of thermally stable zirconia-based mesoporous materials via a facile
      post-treatment.
AB  - A novel method of preparing thermally stable zirconia-based mesoporous materials
      was developed. The zirconia-based mesoporous materials of 2D-hexagonal structure
      were prepared using zirconium sulfate as the zirconium precursor and
      cetyltrimethylammonium (CTMA) as the pore-directing agent with the aid of salt in
      the synthesis solution to reduce the sulfate content in the final product and
      significantly improve the crystallographic ordering. Post-treatment of the
      mesoporous material with NaCl solution and lowering the ramping rate to less than
      0.2 degrees C/min during the calcination process, however, were the key steps to
      hinder the growth of the dense zirconia phase and to retain the ordered
      mesostructure up to 600 degrees C. It was found that a portion of the surfactant
      (8.9-17.4 wt %) and sulfate ions (0.5-1.2 wt %) were removed during the post
      treatment, which prevented the remaining sulfate groups from being reduced by the
      hydrogen-rich surfactant during the calcination process as confirmed by sulfur K
      edge X-ray absorption near edge structure (XANES) and infrared spectroscopy. The
      maintenance of sulfur in the sulfate state seemed to be important in stabilizing
      the mesoporous structure of zirconia materials. The mesoporous zirconia materials
      after extraction with NaCl solution three times and calcination at 550-600
      degrees C had the composition ZrO(2-x)(SO4)x with x = 0.10-0.27. The material
      possesses high surface area (approximately 200 m2/g), large pore volume
      (approximately 0.10 cm3/g), and wormlike mesopores. In comparison with the
      mesoporous zirconia materials stabilized by chemical treatment, the present route
      was simpler and more environmentally friendly and resulted in mesoporous zirconia
      materials of better thermal stability.

PMID- 16800476
TI  - High magnetization helical carbon nanofibers produced by nanoparticle catalysis.
AB  - Helical carbon nanofibers were synthesized by means of acetylene pyrolysis at 450
      degrees C using Fe nanoparticles as catalyst. There is no need to modify the Fe
      nanoparticles by a chiral reagent. The carbon nanofibers generated are
      crystalline and symmetric, with the (110) plane of Fe particle being the mirror
      plane. There would be a change in the shape of the nanofibers if the temperature
      at the beginning or during the synthesis were altered. Compared to the helical
      carbon nanofibers reported elsewhere in the literature, our samples show higher
      magnetization.

PMID- 16800477
TI  - Platinum catalysts prepared with functional carbon nanotube defects and its
      improved catalytic performance for methanol oxidation.
AB  - Carbon nanotube (CNT) supported Pt nanoparticle catalysts have been prepared by
      spontaneous reduction of PtCl6(2-) ion as a result of direct redox reactions
      between PtCl6(2-) and oxygen-containing functional groups at defect sites of
      CNTs, which were introduced by chemical and electrochemical oxidation treatment
      of CNTs. The electrocatalytic properties of as-prepared Pt-CNT catalysts for
      methanol oxidation were investigated by chronopotentiometry and cyclic
      voltammetry. Compared with Pt catalysts prepared by hydrogen reduction and
      electrochemical deposition methods, Pt catalysts synthesized by functional CNT
      defects show excellent antipoisoning ability and long-term cycle stability.

PMID- 16800478
TI  - A new self-consistent empirical interatomic potential model for oxides,
      silicates, and silica-based glasses.
AB  - A new empirical pairwise potential model for ionic and semi-ionic oxides has been
      developed. Its transferability and reliability have been demonstrated by testing
      the potentials toward the prediction of structural and mechanical properties of a
      wide range of silicates of technological and geological importance. The partial
      ionic charge model with a Morse function is used, and it allows the modeling of
      the quenching of melts, silicate glasses, and inorganic crystals at high-pressure
      and high-temperature conditions. The results obtained by molecular dynamics and
      free energy calculations are discussed in relation to the prediction of
      structural and mechanical properties of a series of soda lime silicate glasses.

PMID- 16800479
TI  - Bending contours in silver nanoprisms.
AB  - A detailed electron microscopy analysis is reported on the structure of silver
      nanoprisms synthesized by controlled photoinduced aggregation of Ag
      nanoparticles. Bending of the nanoprism (111) face is directly revealed in the
      presence of fringes in both bright and dark field TEM images, which are
      unequivocally assigned to bending contours. Such contours can be individually
      imaged through shifting of the objective aperture and selectively allowing
      transmission of the corresponding diffraction spot. The assignment of a bent
      structure is supported by images of the lateral sides of the prisms, and high
      resolution images where apparent changes in the lattice constant are observed.

PMID- 16800480
TI  - EPR and solid-state NMR studies of poly(dicarbon monofluoride) (C2F)n.
AB  - Poly(dicarbon monofluoride) (C2F)n was studied by electron paramagnetic resonance
      (EPR) and solid-state nuclear magnetic resonance (NMR). The effects of
      physisorbed oxygen on the EPR and NMR relaxation were underlined and extrapolated
      to poly(carbon monofluoride) (CF)n and semi-covalent graphite fluoride prepared
      at room temperature. Physisorbed oxygen molecules are shown to be an important
      mechanism of both electronic and nuclear relaxations, resulting in apparent spin
      lattice relaxation time and line width during NMR and EPR measurements,
      respectively. The effect of paramagnetic centers on the 19F spin-lattice
      relaxation was underlined in accordance with the high electron spin density
      determined by EPR. 19F magic angle spinning (MAS) NMR, 13C MAS NMR, and 13C MAS
      NMR with 19F to 13C cross polarization (CP) underline the presence of two types
      of carbon atoms, both sp3 hybridized: some covalently bonded to fluorine and the
      others linked exclusively to carbon atoms. Finally, a C-F bond length of 0.138 +/
      0.002 nm has been determined thanks to the re-introduction of dipolar coupling
      using cross polarization.

PMID- 16800481
TI  - pH dependence of the interaction between rhodamine B and the water-soluble
      poly(sodium 4-styrenesulfonate).
AB  - The binding of rhodamine B (RB) to the polyanion containing aromatic groups
      poly(sodium 4-styrenesulfonate) (PSS) is studied by separation and spectroscopic
      techniques at pH between 2 and 7. Significant binding is found at pH below 5,
      together with a red-shift of the RB maximum of absorbance to 564 nm, and RB
      fluorescence quenching. The dependence of the pH is related with protonation of
      RB molecules. Fluorescence quenching is a consequence of a more hydrophobic
      environment and may occur on territorially or site-specifically bound molecules,
      and/or on self-aggregated molecules in a hydrophobic polymer domain. Remarkably,
      the basicity of RB is increased by the influence of the polymer.

PMID- 16800482
TI  - Microcalorimetric Investigation on the lower critical solution temperature
      behavior of N-isopropycrylamide-co-acrylic acid copolymer in aqueous solution.
AB  - The lower critical solution temperature (LCST) behaviors of random and segmented
      copolymers of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) prepared in
      dioxane and water have been investigated by using ultrasensitive microcalorimetry
      (US-DSC). The introduction of AA increases the LCST of the former but slightly
      affects that of the latter. When the molar fraction of AA is low (approximately 2
      mol %), the LCST of the segmented copolymer shifts to a higher temperature with
      increasing pH, while the LCST of the corresponding random copolymer slightly
      changes. Below the boiling point of water, the random copolymer and segmented
      copolymer with the molar fraction of AA about 15 mol % no longer exhibit an LCST
      at pH > 5. The addition of calcium ions leads the LCST of both the segmented
      copolymer and random copolymer to decrease. Our results suggest that the LCST
      behavior of the copolymers is determined by the clustering of poly(N
      isopropylacrylamide) segments.

PMID- 16800483
TI  - Formation of porous carbon materials with in situ generated NaF nanotemplate.
AB  - Porous carbon materials with pore sizes from 3 to 200 nm were synthesized by
      reacting hexafluorobenzene with Na liquid at 623 K. NaF crystals, a byproduct
      formed in the reaction, acted as nanotemplate to assist the pore formation. By
      employing hexafluorobenzene to react with Na incorporated within the channels
      (diameter 200 nm) of anodized aluminum oxide (AAO) membranes at 323-623 K, the
      carbon material can be fabricated into aligned porous nanotube arrays (ca. 250 nm
      in diameter, ca. 20 nm in wall thickness, ca. 0.06 mm in length, and ca. 3-90 nm
      in pore diameter). These materials were characterized by X-ray diffraction,
      scanning and transmission electron microscopy, X-ray energy dispersive
      spectroscopy, electron diffraction, thermal gravimetric analysis, and nitrogen
      physical adsorption experiments.

PMID- 16800484
TI  - Correlating electronic properties of bimetallic surfaces with reaction pathways
      of C2 hydrocarbons.
AB  - The rate and selectivity of chemical reactions on transition-metal surfaces can
      be controlled by using different bimetallic combinations. The interaction of
      bimetallic components leads to a change in the electronic properties of the
      surface, which in turn produces a change in chemical reactivity. In the current
      paper, we illustrate the correlation of the electronic properties of bimetallic
      surfaces with the reaction pathways of C2 hydrocarbons. Density functional theory
      (DFT) was used to study the binding of hydrogen, ethylene, acetylene, ethyl, and
      vinyl on monometallic and bimetallic transition-metal surfaces. The binding
      energies of these species were found to correlate with the d-band centers of
      these surfaces. The binding energies for hydrogen atoms on bimetallic surfaces
      were lower than for those on the corresponding parent metal surfaces. This trend
      was consistent for ethylene and acetylene binding. Comparative studies between
      acetylene and ethylene revealed that acetylene was more strongly bonded to the
      monometallic and the bimetallic surfaces than was ethylene. Bond order
      conservation (BOC) theory was used to calculate the activation barriers for ethyl
      dehydrogenation to ethylene and vinyl dehydrogenation to acetylene. The
      activation barriers for these reactions were correlated with the surface d-band
      center of the substrates.

PMID- 16800485
TI  - Physicochemical aspects of novel surfactantless, self-templated mesoporous SnO2
      thin films.
AB  - A novel method of synthesis consisting of the production of ordered arrangements
      of tubular pores distributed inside SnO2 annealed thin films, which are prepared
      from a rotating disk process carried out at 2000-3500 rpm, is herein described.
      The main novelty is that no surfactant molecules are required in order to create
      these ordered pore structures; the templating entities are supramolecular
      assemblies of oligomeric chains formed during the extra-long aging allowed to the
      sol-gel processing of tin(IV) tetra-tert-amiloxide, Sn(OAm(t))4, chelated with
      acetylacetone molecules. Low angle X-ray diffraction peaks of SnO2 thin films
      calcined at 500 degrees C clearly certify the existence of ordered mesostructures
      when employing the right H2O/Sn(OAm(t))4 molar ratio during the SnO2 sol-gel
      synthesis. The final SnO2 ordered mesostructures are reminiscent of those linked
      to MCM-41 and SBA-15 substrates. Pore-size distribution analyses proceeding from
      N2 sorption isotherms at 76 K on the SnO2 thin films calcined at 500 degrees C
      unequivocally confirm the presence of tubular mesopores (mode pore sizes ranging
      from 5 to 7 nm). The thicknesses of the SnO2 films range from 80 to 150 nm after
      performing a drying process at 100 degrees C and from 70 to 125 nm after
      calcining in air at 500 degrees C; these film thicknesses show, in general,
      decreasing trends when either the spinning rate or the H2O/(Sn(OAm(t))4 ratio is
      increased.

PMID- 16800486
TI  - New insights on the behavior of PRODAN in homogeneous media and in large
      unilamellar vesicles.
AB  - The behavior of 6-propionyl-2-dimethylaminonaphthalene (PRODAN) was studied in
      homogeneous media and in large unilamellar vesicles (LUVs) of the phospholipid
      1,2-di-oleoyl-sn-glycero-3-phosphatidylcholine (DOPC), using absorption,
      emission, depolarization, and time-resolved spectroscopies. In homogeneous media,
      the Kamlet and Taft solvatochromic comparison method quantified solute-solvent
      interactions from the absorption and emission PRODAN bands. These studies
      demonstrate that the absorption band is sensitive to the polarity-polarizability
      (pi) and the hydrogen bond donor ability (alpha) parameters of the media. PRODAN
      in the excited state is even more sensitive to these parameters and to the
      hydrogen bond acceptor ability (beta) of the media. The transition energy
      (expressed in kcal/mol) for both absorption and emission bands gives a linear
      correlation with the well-known polarity parameter E(T30). The results from the
      absorption and emission bands also reveal that PRODAN aggregates in water. The
      monomer has two fluorescence lifetimes, 2.27 and 0.65 ns, while the aggregate has
      a lifetime of 14.6 ns. Using steady-state anisotropy measurements, the calculated
      volumes of the aggregate and the monomer are 5590 and 222 mL mol(-1),
      respectively. In DOPC LUVs, PRODAN undergoes a partition process between the
      water bulk and the DOPC bilayer. We show that the partition constant (K(p)) value
      is large enough that only at [DOPC] below 0.15 mg/mL PRODAN in water can be
      detected. PRODAN dissolved in LUVs at [DOPC] > 1 mg/mL exists completely
      incorporated in its monomer form and senses two different microenvironments
      within the bilayer: a polar region in the interface near the water and a less
      polar and also less viscous environment, between the phospholipid tails. These
      environments were characterized by their fluorescence lifetimes (tau), showing
      that PRODAN in the polar microenvironment has a tau value of approximately 4 ns
      while in the less polar region gives a value of 1.2 ns. Moreover, this probe also
      senses the micropolarity of these two different regions of the bilayer and yields
      values similar to that of methanol and tetrahydrofuran.

PMID- 16800487
TI  - Methanol adsorption on the beta-Ga2O3 surface with oxygen vacancies: theoretical
      and experimental approach.
AB  - Methanol adsorption on beta-Ga2O3 surface has been studied by Fourier transform
      infrared spectroscopy (FTIR) and by means of density functional theory (DFT)
      cluster model calculations. Adsorption sites of tetrahedral and octahedral
      gallium ions with different numbers of oxygen vacancies have been compared. The
      electronic properties of the adsorbed molecules have been monitored by computing
      adsorption energies, optimized geometry parameters, overlap populations, atomic
      charges, and vibrational frequencies. The gallia-methanol interaction has
      different behaviors according to the local surface chemical composition. The
      calculations show that methanol can react in three different ways with the gallia
      surface giving rise to a nondissociative adsorption, a dissociative adsorption,
      and an oxidative decomposition. The surface without oxygen vacancies is very
      reactive and produces the methanol molecule decomposition. The molecule is
      nondissociatively adsorbed by means of a hydrogen bond between the alcoholic
      hydrogen atom and a surface oxygen atom and a bond between the alcoholic oxygen
      atom and a surface gallium atom. Two neighbor oxygen vacancies on tetrahedral
      gallium sites produce the dissociation of the methanol molecule and the formation
      of a bridge bond between two surface gallium atoms and the methoxy group.

PMID- 16800488
TI  - Reduction features of NO over a potassium-doped C12A7-O- catalyst.
AB  - The NO reduction features over a noble-metal-free NO(x) storage/reduction
      catalyst ([Ca24Al28O64](4+*)4O-/K, defined as C12A7-O-/K), including the NO
      conversion, the N2 selectivity, and sulfur tolerance, were investigated with
      hydrogen and C3H6 as the reducing agents in a fixed-bed continuous flow reactor.
      The NO conversion and the N2 selectivity on the C12A7-O-/K catalyst mainly
      depends on the sample temperature, the percentage of potassium, the reducing
      agents, and the composition of the mixture of gases. The C12A7-O-/10%K catalyst
      possessed the highest selective reduction ability (to N2) among the catalysts
      C12A7-O-/x%K. Over 50% of NO can be reduced to N2 with H2 as the reduction agent
      at 550-700 degrees C. The C12A7-O-/K catalyst also shows higher NO(x) storage
      capacity (183.9 micromol/g at about 550 degrees C) as well as sulfur tolerance
      for both the NO(x) storage and the reduction processes. The catalyst
      characteristics and the intermediate species formed in the NO storage and
      reduction processes were investigated by the X-ray diffraction, X-ray
      photoelectron spectroscopy, Fourier transform infrared spectroscopy, and time-of
      flight mass spectrometry. The mechanism of NO(x) reduction was addressed
      according to the above investigations.

PMID- 16800489
TI  - Dynamics of energy transfer in collisions of O(3P) atoms with a 1-decanethiol
      self-assembled monolayer surface.
AB  - Chemical dynamics simulations are reported of energy transfer in collisions of
      O(3P) atoms with a 300 K 1-decanethiol self-assembled monolayer (H-SAM) surface.
      The simulations are performed with a nonreactive potential energy surface,
      developed from PMP2/aug-cc-pVTZ calculations of the O(3P) + H-SAM intermolecular
      potential, and the simulation results represent the energy transfer dynamics in
      the absence of O(3P) reaction. Collisions energies E(i) of 0.12, 2.30, 11.2,
      75.0, and 120.5 kcal/mol and incident angles theta(i) of 15, 30, 45, 60, and 75
      degrees were considered in the study (theta(i) = 0 degrees is the surface
      normal). The translational energy distribution of the scattered O(3P) atoms,
      P(E(f)), may be deconvoluted into Boltzmann and non-Boltzmann components, with
      the former fraction identified as f(B). The trajectories are also analyzed in
      terms of three types; that is, direct scattering from and physisorption on the
      top of the H-SAM and penetration of the H-SAM. There are three energy regimes in
      the scattering dynamics. For the low E(i) values of 0.12 and 2.30 kcal/mol,
      physisorption is important and both f(B) and the average final translational
      energy of the scattered O(3P) atom, E(f), are nearly independent of the incident
      angle. The dynamics is much different for hyperthermal energies of 75.0 and 120.5
      kcal/mol, where penetration of the surface is important. For hyperthermal
      collisions, the penetration probability decreases as theta(i) is increased, with
      a significant transition between theta(i) of 60 and 75 degrees . Hyperthermal
      penetration occurs upon initial surface impact and is more probable if the
      impinging O(3P) atom may move down a channel between the chains. For E(i) = 120.5
      kcal/mol, 90% of the trajectories penetrate at theta(i) = 15 degrees , while only
      3% penetrate at theta(i) = 75 degrees. For the former theta(i), the energy
      transfer to the surface is efficient with E(f) = 4.04 kcal/mol, but for the
      latter theta(i), E(f) = 85.3 kcal/mol! Particularly interesting penetrating
      trajectories are those in which O(3P) is trapped in the H-SAM for times exceeding
      60 ps, linger near the Au substrate, and strike the Au substrate and scatter
      directly. For E(i) = 11.2 kcal/mol, there is a transition between the scattering
      dynamics for the low and hyperthermal collision energies. Additional detail in
      the energy transfer dynamics is obtained from the final polar and azimuthal
      angles, the residence time on/in the H-SAM, the minimum height with respect to
      the Au substrate, and the number of inner turning points in the O-atom's
      velocity. Calculated values of E(f) vs the final polar angle, theta(f), are in
      qualitative agreement with experiment. The O(3P) + H-SAM nonreactive energy
      transfer dynamics, for E(i) of 11.2 kcal/mol and lower, are very similar to
      previously reported Ne + H-SAM simulations.

PMID- 16800490
TI  - Morphological evolution of Ba(NO3)2 supported on alpha-Al2O3(0001): an in situ
      TEM study.
AB  - A key question for the BaO-based NOx storage/reduction catalyst system is the
      morphological evolution of the catalyst particles during the uptake and release
      of NOx. Notably, because the formed product during NOx uptake, Ba(NO3)2, requires
      a lattice expansion from BaO, one can anticipate that significant structural
      rearrangements are possible during the storage/reduction processes. Associated
      with the small crystallite size of high-surface area gamma-Al2O3, it is difficult
      to extract structural and morphological features of Ba(NO3)2 supported on gamma
      Al2O3 by any direct imaging method, including transmission electron microscopy.
      In this work, by choosing a model system of Ba(NO3)2 particles supported on
      single-crystal alpha-Al2O3, we have investigated the structural and morphological
      features of Ba(NO3)2 as well as the formation of BaO from Ba(NO3)2 during the
      thermal release of NOx, using ex-situ and in-situ TEM imaging, electron
      diffraction, energy dispersive spectroscopy (EDS), and Wulff shape construction.
      We find that Ba(NO3)2 supported on alpha-Al2O3 possesses a platelet morphology,
      with the interface and facets being invariably the eight [111] planes. Formation
      of the platelet structure leads to an enlarged interface area between Ba(NO3)2
      and alpha-Al2O3, indicating that the interfacial energy is lower than the
      Ba(NO3)2 surface free energy. In fact, Wulff shape constructions indicate that
      the interfacial energy is approximately 1/4 of the [111] surface free energy of
      Ba(NO3)2. The orientation relationship between Ba(NO3)2 and the alpha-Al2O3 is
      alpha-Al2O3[0001]//Ba(NO3)2[111] and alpha-Al2O3(1-210)//Ba(NO3)2(110). Thus, the
      results clearly demonstrate dramatic morphology changes in these materials during
      NOx release processes. Such changes are expected to have significant consequences
      for the operation of the practical NOx storage/reduction catalyst technology.

PMID- 16800491
TI  - The deformation and adhesion of randomly rough and patterned surfaces.
AB  - Using a surface forces apparatus (SFA) and an atomic force microscope (AFM) we
      have studied the effects of surface roughness (root-mean-square (RMS) roughness
      between 0.3 and 220 nm) on the "contact mechanics", which describes the
      deformations and loading and unloading adhesion forces, of various polymeric
      surfaces. For randomly rough, moderately stiff, elastomeric surfaces, the force
      distance curves on approach and separation are nearly reversible and almost
      perfectly exponentially repulsive, with an adhesion on separation that decreases
      only slightly with increasing RMS. Additionally, the magnitude of the preload
      force is seen to play a large role in determining the measured adhesion. The
      exponential repulsion likely arises from the local compressions (fine-grained
      nano- or submicron-scale deformations) of the surface asperities. The resulting
      characteristic decay lengths of the repulsion scale with the RMS roughness and
      correlate very well with a simple finite element method (FEM) analysis based on
      actual AFM topographical images of the surfaces. For "patterned" surfaces, with a
      nonrandom terraced structure, no similar exponential repulsion is observed,
      suggesting that asperity height variability or random roughness is required for
      the exponential behavior. However, the adhesion force or energy between two
      "patterned" surfaces fell off dramatically and roughly exponentially as the RMS
      increased, likely owing to a significant decrease in the contact area which in
      turn determines their adhesion. For both types of rough surfaces, random and
      patterned, the coarse-grained (global, meso- or macroscopic) deformations of the
      initially curved surfaces appear to be Hertzian.

PMID- 16800492
TI  - A systematic study of the structure and bonding of halogens on low-index
      transition metal surfaces.
AB  - The structure and bonding of halogens on various transition metal low-index
      surfaces has been studied by means of density functional theory (DFT)
      calculations using periodic slabs to model the surface. This approach is shown to
      be capable of reproducing available experimental data of naked and halogen
      covered surfaces. Periodic trends are discerned and discussed for several
      properties, including metal-halogen bond distances and vibrational frequencies,
      adsorption energies, and bond ionicities, which have been evaluated by a Bader
      population analysis of the corresponding density. A simple correlation is
      discerned, relating the bond ionicity to the metal work function, so that higher
      work function surfaces are associated with more covalent bonding. Periodic trends
      in bond ionicities and metal-halogen vibrational frequencies are in harmony with
      corresponding data derived in an electrochemical environment, indicating that the
      metal-halogen bonding in vacuum share some features with the electrode metal
      surface-halogen bonding.

PMID- 16800493
TI  - The pressure- and temperature-induced wetting transitions in the binary water +
      ethylene glycol monoisobutyl ether mixture.
AB  - A homemade pendent drop/bubble tensiometer is applied to perform the
      surface/interfacial tension measurements for the binary water + ethylene glycol
      monoisobutyl ether (iso-C4E1) mixture over the temperature range from 25 to 150
      degrees C and over the pressure range up to 100 bar. The symbol C(i)E(j) is the
      abbreviation of a nonionic polyoxyethylene alcohol C(i)H(2i+1)(OCH2CH2)(j)OH. The
      wetting behavior of the iso-C4E1-rich phase at the surface of the aqueous phase
      is systematically examined according to the wetting coefficient determined from
      the experimental results of surface/interfacial tensions. It is found that the
      iso-C4E1-rich phase exhibits a sequence of wetting transitions, nonwetting -->
      partial wetting --> complete wetting, at the water surface in the water + iso
      C4E1 system along with increasing temperature. On the other hand, the iso-C4E1
      rich phase undergoes a wetting transition from partial wetting to nonwetting at
      the surface of the aqueous phase by increasing the system pressure at a fixed
      temperature near the lower critical solution temperature (LCST) of the closed
      loop miscibility gap in the water + iso-C4E1 system.

PMID- 16800494
TI  - Potential oscillations in galvanostatic electrooxidation of formic acid on
      platinum: a mathematical modeling and simulation.
AB  - We have modeled temporal potential oscillations during the electrooxidation of
      formic acid on platinum on the basis of the experimental results obtained by time
      resolved surface-enhanced infrared absorption spectroscopy (J. Phys. Chem. B
      2005, 109, 23509). The model was constructed within the framework of the so
      called dual-path mechanism; a direct path via a reactive intermediate and an
      indirect path via strongly bonded CO formed by dehydration of formic acid. The
      model differs from earlier ones in the intermediate in the direct path. The
      reactive intermediate in this model is formate, and the oxidation of formate to
      CO2 is rate-determining. The reaction rate of the latter process is represented
      by a second-order rate equation. Simulations using this model well reproduce the
      experimentally observed oscillation patterns and the temporal changes in the
      coverages of the adsorbed formate and CO. Most properties of the voltammetric
      behavior of formic acid, including the potential dependence of adsorbate
      coverages and a negative differential resistance, are also reproduced.

PMID- 16800495
TI  - EPR study of the surface basicity of calcium oxide. 3. Surface reactivity and
      nonstoichiometry.
AB  - High surface area polycrystalline calcium oxide forms ozonide O3- ions upon O2
      adsorption and NO3(2-) anions under low pressures of NO. Both radical anions,
      detected by electron paramagnetic resonance (EPR), are not observed in the case
      of the homologous magnesium oxide. This behavior reveals the presence, in CaO, of
      anomalies with respect to the ideal composition of an ionic oxide which are
      identified in terms of two main types of defects. The first type consists of
      positive holes dispersed in the bulk and originated by the unavoidable presence
      of Na+ ions in the composition of the solid. The decomposition of the surface
      ozonide shows the formation of a transient surface stabilized O- (the chemical
      notation of a positive hole associated to an oxide ion) which is for the first
      time reported at the surface of CaO. The second type of defect consists of
      surface peroxide groups (present at particular surface sites where they are
      formed by pairing of two distinct O-) which react with nitric oxide (NO) yielding
      NO3(2-) radical anions. The presence of peroxide is not related to the presence
      of impurities but, rather, to a certain propensity of the solid to form such ions
      at the surface along the dehydration process.

PMID- 16800496
TI  - Characterization and catalytic performances of three-dimensional mesoporous FeSBA
      1 catalysts.
AB  - Iron substituted cubic cage type mesoporous molecular sieves (FeSBA-1) were
      synthesized for the first time in a highly acidic media using
      cetyltriethylammonium bromide as a template. The amount of Fe incorporation in
      SBA-1 can easily be controlled by the simple adjustment of the molar hydrochloric
      acid-to-silicon ratio. All the materials were unambiguously characterized by AAS,
      XRD, N2 adsorption, UV-Vis DRS, XPS, and ESR spectroscopy. The results from AAS,
      XRD, and N2 adsorption reveal that the iron atom can be incorporated in the
      framework of SBA-1 matrix without altering the structural order and the textural
      parameters. The nature and the coordination of iron atoms were extensively
      studied by XPS spectroscopy, and the results revealed that most of the iron atoms
      in FeSBA-1 are in +3 coordination state. UV-Vis DRS and ESR studies confirmed
      that the majority of the Fe atoms in FeSBA-1 exist in a tetrahedral coordination
      environment (most probably occupying framework positions). tert-Butylation of
      phenol employing tert-butanol as the alkylation agent was carried out over FeSBA
      1 catalysts with different iron content and the results are compared with one
      dimensional mesoporous catalysts. The influence of various reaction parameters
      such as reaction temperature, reactant feed ratio, weight hourly space velocity,
      and time-on-stream affecting the activity and selectivity of FeSBA-1 were also
      studied. Under the optimized reaction conditions, the FeSBA-1(36) catalyst showed
      superior catalytic performance for the tert-butylation of phenol as compared to
      the uni-dimensional mesoporous catalysts.

PMID- 16800497
TI  - Optimal binding site of a methane molecule on the silanol covered (010) surface
      of silicalite-1: ONIOM calculations.
AB  - The binding energies and the corresponding structures of a methane molecule on
      the silanol covered (010) surface of silicalite-1 have been investigated using ab
      initio methods. Different levels of calculations, HF/6-31G(d), MP2/6-31G(d) and
      ONIOM (MP2/6-31G(d):HF/6-31G(d)) including the correction of an error due to an
      unbalance of the basis set, known as basis set super position error (BSSE), as
      well as the size of the cluster representing the silicalite-1 surface, were
      systematically examined to validate the model used. The ONIOM method with the
      BSSE correction was found to be a compromise between accuracy and computer time
      required. The optimal binding site on the silicalite-1 surface was observed at
      the configuration where the methane molecule points one H atom toward the O atom
      of the silanol group. The corresponding binding energy is -1.71 kJ/mol. This
      value is significantly higher than that of -5.65 kJ/mol when the methane molecule
      approaches the center of the straight channel. At this configuration, the C atom
      of methane was observed to locate exactly at the center of the channel. This
      leads to the conclusion that the methane molecule will relatively seldom be
      adsorbed on the silanol covered (010) surface of silicalite-1. Instead, the
      adsorption process will take place directly at the center of the straight
      channel.

PMID- 16800498
TI  - Potential-dependent sum frequency generation study of 5-methylbenzotriazole on
      polycrystalline copper, platinum, and gold.
AB  - In situ sum frequency generation vibrational spectroscopy, at varied potentials
      and polarization combinations, was performed on polycrystalline copper,
      polycrystalline platinum, and polycrystalline gold samples in 0.5 M HClO4 with 50
      mM 5-methylbenzotriazole (5-methylBTAH) added. These studies were performed to
      determine the orientation of 5-methylBTAH on the surface at different potentials.
      For copper surfaces, orientation of the molecule on the surface is not affected
      by potential within the potential window studied (-500 to -100 mV vs saturated
      calomel electrode (SCE)). Sum frequency generation spectra of 5-methylBTAH on
      platinum show a change in orientation over the potential range studied (-250 to
      750 mV vs SCE). The orientation of the methyl group tilts more toward the plane
      of the interface as the potential is scanned in the positive direction. This
      orientation change is correlated to hydrogen coadsorption on the platinum surface
      at low potentials. 5-Methylbenzotriazole lies in the surface plane or does not
      orient on gold at lower potentials but the orientation is tilted toward normal at
      more positive potentials over the potential range studied (-500 to 900 mV vs
      SCE). To compliment these results, cyclic voltammetry and electrochemical
      impedance spectroscopy measurements were performed. Cyclic voltammograms of
      copper show that addition of 5-methylBTAH protects the surface from copper
      dissolution, increasing the electrochemical window by 450 mV. Cyclic voltammetry
      of 5-methylBTAH on platinum showed a partial blockage of adsorbed hydrogen and
      also prevented the adsorption of oxygenated species at 450-600 mV. Cyclic
      voltammetry on gold shows that 5-methylBTAH blocks oxide formation for 400 mV
      thus increasing the electrochemical window. Electrochemical impedance
      spectroscopy has been performed to determine the potential of zero charge of 5
      methylBTAH on copper.

PMID- 16800499
TI  - Mechanisms of oscillations and formation of nano-scale layered structures in
      induced co-deposition of some iron-group alloys (Ni-P, Ni-W, and Co-W), studied
      by an in situ electrochemical quartz crystal microbalance technique.
AB  - We have investigated mechanisms of oscillations and formation of nano-scale
      layered structures in induced co-deposition of some iron-group alloys (Ni-P, Ni
      W, and Co-W) that have unique properties and are widely used in industries.
      Detailed in situ electrochemical quartz crystal microbalance (EQCM) experiments
      have revealed that the electrodeposition (induced co-deposition) of the alloys
      has negative differential resistances (NDRs), from which the oscillations and the
      layer-structure formation arise. The NDRs, however, cannot necessarily be seen in
      current-potential curves owing to overlap of hydrogen evolution current,
      indicating that the oscillations are of a hidden-NDR (H-NDR) type. The EQCM
      experiments have also shown that electrolyte components (such as H2PO2- and WO4(2
      )) or related species are adsorbed at the electrode (deposit) surface and act as
      a promoter for the co-deposition reaction and that the NDRs arise from desorption
      of the adsorbed promoter. Interestingly, the adsorbed promoter is drawn into the
      deposition reaction itself, thus resulting in the alloy deposits. This mechanism
      was supported by in situ EQCM investigations of the oscillation as well as Auger
      electron spectroscopic (AES) analyses of deposits formed during the oscillation.
      The present work has for the first time clarified a general mechanism for the
      induced co-deposition reactions of some industrially important iron-group alloys
      (Ni-P, Ni-W, and Co-W).

PMID- 16800500
TI  - Electrostatic stability of a large collection of charged anisotropic
      nanoparticles: a monte carlo study exploiting a hierarchical approach.
AB  - We have performed Monte Carlo simulations of the self-organization of large
      collections of charged disks of various electric charges to probe the influence
      of electrostatic coupling on the structure and the mechanical stability of
      aqueous dispersions of charged anisotropic nanoparticles in the presence of salt.
      A hierarchical approach of the long-range Coulombic potential was used to perform
      such Monte Carlo simulations of a large number of charged species. By analyzing
      the influence of the net electric charge of the disks on their self-organization,
      we detected a negative contribution to the mean force potential resulting from
      their electrostatic coupling. In addition, it has been shown that the same
      electrostatic coupling restricts the spatial extend of locally ordered
      microdomains within dilute dispersions of charged anisotropic colloids.

PMID- 16800501
TI  - Uptake of n-hexane, 1-butene, and toluene by Au/Pt bimetallic surfaces: a tool
      for selective sensing of hydrocarbons under high-vacuum conditions.
AB  - The dissociative adsorption and decomposition on a range of metal surfaces of an
      alkane, an alkene, and an aromatic, all representative of species present in an
      important technological application, has been studied under conditions relevant
      to selective gas sensing based on solid electrolyte potentiometry. At 870 K, pure
      polycrystalline Pt surfaces do not discriminate between n-hexane, toluene, and 1
      butene: graphitic carbon accumulation occurs at almost the same rate. However, by
      varying the composition of polycrystalline bimetallic Pt/Au surfaces, good
      discrimination between these species can be achieved. Thus at a nominal surface
      composition of approximately 75% Au (XPS), good selectivity toward 1-butene and
      toluene uptake is achieved, with essentially no response to n-hexane. At
      approximately 80% Au the system is selective to 1-butene alone. Particular merits
      of these systems include good high-temperature stability and good tunability of
      their chemical selectivity. This makes possible the development of array devices
      in which the elements have overlapping but different selectivity profiles.

PMID- 16800502
TI  - Ridge-bridge adsorption of molecular oxygen on Pt[110](1 x 2) from first
      principles.
AB  - The chemisorption of molecular oxygen on the missing-row reconstructed Pt[110](1
      x 2) surface has been investigated using ab initio calculations based on spin
      density functional theory. The calculated energetic, structural, vibrational, and
      electronic properties of the chemisorbed O2 species are discussed in terms of the
      available experimental data. We find that adsorption in the ridge-bridge site is
      strongly preferred on energetic grounds, relative to adsorption on the [111]
      microfacets or in the valley sites of the reconstructed surface. We argue in
      favor of initial adsorption in the ridge-bridge sites, followed by adsorption in
      the valley long-bridge sites at higher coverages, without excluding the
      possibility of bridge-site adsorption on the [111] microfacets.

PMID- 16800503
TI  - Surface segregation of dissolved salt ions.
AB  - Surface segregation of iodide, but not of fluoride or cesium ions, is observed by
      a combination of metastable impact electron spectroscopy (MIES) and ultraviolet
      photoelectron spectroscopy (UPS(HeI)) of amorphous solid water exposed to CsI or
      CsF vapor. The same surface ionic behavior is also derived from molecular
      dynamics (MD) simulations of the corresponding aqueous salt solutions. The MIES
      results show the propensity of iodide, but not fluoride, for the surface of the
      amorphous solid water film, providing thus strong evidence for the suggested
      presence of heavier halides (iodide, bromide, and to a lesser extent chloride) at
      the topmost layer of aqueous surfaces. In contrast, no appreciable surface
      segregation of ions is observed in methanol, neither in the experiment nor in the
      simulation. Furthermore, the present results indicate that, as far as the
      thermodynamic aspects of solvation of alkali halides are concerned, amorphous
      solid water and methanol surfaces behave similarly as surfaces of the
      corresponding liquids.

PMID- 16800504
TI  - Mechanism for NO2 charging on metal supported MgO.
AB  - NO2 adsorbed on MgO(100) supported by Ag or Pt is explored by density functional
      theory calculations. NO2 is weakly adsorbed on MgO(100), with a bond involving
      minor oxide to adsorbate charge transfer. However, if MgO is supported, then the
      adsorption energy is considerably enhanced and NO2 is adsorbed as a nitrite (N).
      Analysis reveals that the NO2 excess charge originates from the oxide side of the
      oxide/metal interface and that the electron abstraction increases the oxide/metal
      adhesion. The proposed mechanism is general and should apply for oxidizing
      surface species.

PMID- 16800505
TI  - On the size-dependent behavior of nanocrystal-ligand bonds.
AB  - Recent experiments have indicated that 3-mercapto-1-propanol ligands display a
      size-dependent binding energy of attachment to the surface of II-VI semiconductor
      nanocrystals. Using semiempirical calculations, we exhaustively calculate the
      energy of this bond at each surface site, for CdSe and CdSe/CdS core/shell
      nanocrystals ranging from 1.8 to 4.1 nm in diameter. Our results suggest that the
      experimentally observed changes in binding energy are due to the distribution of
      surface facets on the nanocrystals, and not related to the band gap, as proposed
      in the experimental paper.

PMID- 16800506
TI  - Microfabrication using elastomeric stamp deformation.
AB  - Elastomeric stamp deformation has been utilized for the contact printing (CP) of
      self-assembled monolayers (SAMs) and, more recently, polymers and proteins. Here,
      we take advantage of this well-studied phenomenon to fabricate a series of new
      metal thin-film patterns not present on the original stamp. The rounded patterns
      are of nanoscale thickness, long-range order, and are created from elastomeric
      stamps with only straight-edged features. The metal was printed onto the surface
      of an alpha,omega-alkanedithiol self-assembled monolayer (SAM). The new shapes
      are controlled by a combination of stamp geometry design and the application of
      external pressure. Previously published rules on stamp deformation for contact
      printing of SAMs are invalid because the coating is instead a thin-metal film.
      This method represents a new pathway to micropatterning metal thin films, leading
      to shapes with higher complexity than the original lithographic masters.

PMID- 16800507
TI  - Role of conformation in the electronic properties of chemisorbed pyridine on
      Cu(110): an STM/STS study.
AB  - Pyridine was chemisorbed on Cu(110) at 10 K and observed using STM at 5 K as
      dosed and after annealing to temperatures between 20 and 300 K. At very low
      coverage, two molecular species with different apparent heights are observed to
      coexist. The higher species is assigned to a pyridine molecule bonded with its
      symmetry axis perpendicular to the surface plane, while the lower species is
      assigned to a pyridine molecule that is tilted down toward the surface plane. At
      low coverage, the tilted pyridine species predominates on the surface, but as the
      total surface coverage of pyridine increases, the molecules stand up until the
      upright geometry becomes favored. Measurements of the STS of the two species show
      different molecular resonances derived from the lowest unoccupied pyridine pi*
      orbitals. The tilted pyridine species has a peak in the unoccupied local density
      of states at 2.6 +/- 0.1 eV, whereas the upright pyridine species has a peak at
      2.3 +/- 0.1 eV.

PMID- 16800509
TI  - FTIR spectroscopy combined with isotope labeling and quantum chemical
      calculations to investigate adsorbed bicarbonate formation following reaction of
      carbon dioxide with surface hydroxyl groups on Fe2O3 and Al2O3.
AB  - FTIR spectroscopy combined with isotope labeling experiments and quantum chemical
      calculations is used to investigate the adsorption of carbon dioxide on
      hydroxylated metal oxide surfaces. In particular, transmission FTIR spectra
      following CO2 adsorption on hydroxylated nanoparticulate Fe2O3, alpha-Al2O3, and
      gamma-Al2O3 particles at 296 K are reported. As expected, reaction of CO2 with
      these surfaces results in the formation of adsorbed bicarbonate and carbonate. In
      this study, the vibrational spectrum of the bicarbonate product is analyzed in
      detail through the use of isotope labeling experiments and quantum chemical
      calculations. The experimental and calculated vibrational frequencies of adsorbed
      HC16O3-, DC16O3-, HC18O3-, HC16O18O2-, and HC18O16O2- indicate that bicarbonate
      bonds to the surface in a bridged structure. There is some evidence from the
      mixed isotope experiments that following initial nucleophilic attack of OH, the
      formation of the final bicarbonate structure involves a proton transfer. On the
      basis of energetic considerations, the proton transfer mechanism most likely
      occurs through an intermolecular process involving either coadsorbed hydroxyl
      groups and/or carbonate.

PMID- 16800508
TI  - Biphasic tautomerization dynamics of excited 7-hydroxyquinoline in reverse
      micelles.
AB  - The excited-state tautomerization dynamics of 7-hydroxyquinoline in the water
      pools of reverse micelles has been investigated by monitoring time-resolved
      fluorescence spectra and kinetics as well as static absorption and emission
      spectra with a variation of water content and isotopic fractionation. The normal
      and the tautomeric species are found to reside preferentially in the bound- and
      the free-water regions of the micelles, respectively. The excited-state
      tautomerization of the normal species in the bound-water layers is suggested to
      occur via two different channels, depending on rotamers at the moment of
      excitation. The cis tautomerizes via proton relay from the enol group to the
      imino group along a hydrogen-bonded water bridge, unusual in water but common in
      alcohols, whereas the trans tautomerizes via the stepwise individual acid-base
      reactions of two prototropic groups as found in bulk water. Proton relay can take
      place because water in the pools has substantially reduced polarity and disrupted
      hydrogen-bond networks compared with bulk water.

PMID- 16800510
TI  - Sodium chloride-catalyzed oxidation of multiwalled carbon nanotubes for
      environmental benefit.
AB  - A sodium chloride (NaCl) catalyst (0.1 w/w %) lowers the oxidation temperature of
      graphitized multiwalled carbon nanotubes: MWCNT-20 (diameter: 20-70 nm) and MWCNT
      80 (diameter: 80-150 nm). The analysis of the reaction kinetics indicates that
      the oxidation of MWCNT-20 and MWCNT-80 mixed with no NaCl exhibits single
      reaction processes with activation energies of E(a) = 159 and 152 kJ mol(-1),
      respectively. The oxidation reaction in the presence of NaCl is shown to consist
      of two different reaction processes, that is, a first reaction and a second
      reaction process. The first reaction process is dominant at a low temperature of
      around 600 degrees C, while the second reaction process becomes more dominant
      than the first one in a higher temperature region. The activation energies of the
      first reaction processes (MWCNT-20: E(a1) = 35.7 kJ mol(-1); MWCNT-80: E(a1) =
      43.5 kJ mol(-1)) are much smaller than those of the second reaction processes
      (MWCNT-20: E(a2) = 170 kJ mol(-1); MWCNT-80: E(a2) = 171 kJ mol(-1)). The
      comparison of the kinetic parameters and the results of the spectroscopic and
      microscopic analyses imply that the lowering of the oxidation temperature in the
      presence of NaCl results from the introduction of disorder into the graphitized
      MWCNTs (during the first reaction process), thus increasing the facility of the
      oxidation reaction of the disorder-induced nanotubes (in the second reaction
      process). It is found that the larger nanopits and cracks on the outer graphitic
      layers are caused by the catalytic effect of NaCl. Therefore, the NaCl-mixed
      samples showed more rapid and stronger oxidation compared with that of the
      nonmixed samples at the same residual quantity.

PMID- 16800511
TI  - Interfacial water on Cl- and H-terminated Si(111) surfaces from first-principles
      calculations.
AB  - The properties of interfacial water on Cl- and H-terminated Si(111) surfaces are
      investigated using a first-principles approach and characterized by means of
      energetic analysis combined with hydrogen-bond counting. The interaction of water
      with both substrates is found to be significantly weak, although bonding with the
      Cl-terminated Si(111) surface is relatively stronger because of the electrostatic
      contribution. According to a molecular picture for attributing the
      hydrophilic/hydrophobic character, both surfaces should be considered
      hydrophobic, at variance with the interpretation of recent ultrafast electron
      crystallography experiments, which seems instead to support a hydrophilic nature
      of the Cl-terminated Si(111) substrate.

PMID- 16800512
TI  - Effect of substrate on surface-enhanced Raman scattering of molecules adsorbed on
      immobilized silver nanoparticles.
AB  - Silver nanoparticles were assembled on polyvinylpyridine (PVP) derivatized glass
      slides. Charge transfer between the adsorbed 4-aminothiophenol (PATP) and the
      immobilized silver nanoparticles was studied by surface-enhanced Raman
      spectroscopy with 1064 nm excitation, and compared with that of the silver
      nanoparticles in the colloid. It was demonstrated that the positive charges of
      the PVP layer could alter the charge distribution in the immobilized
      nanoparticles and induce the formation of the dipole in the nanoparticles,
      leading to less charge transfer from the metal to the adsorbed molecules. The
      coadsorption of chloride ions on the surface of the immobilized silver
      nanoparticles resulted in the redistribution of the charges in the nanoparticles
      and, in turn, altered the charge transfer between the adsorbed PATP molecules and
      the silver nanoparticles.

PMID- 16800513
TI  - Continuum solvation models in the linear interaction energy method.
AB  - The linear interaction energy (LIE) method in combination with two different
      continuum solvent models has been applied to calculate protein-ligand binding
      free energies for a set of inhibitors against the malarial aspartic protease
      plasmepsin II. Ligand-water interaction energies are calculated from both Poisson
      Boltzmann (PB) and Generalized Born (GB) continuum models using snapshots from
      explicit solvent simulations of the ligand and protein-ligand complex. These are
      compared to explicit solvent calculations, and we find close agreement between
      the explicit water and PB solvation models. The GB model overestimates the change
      in solvation energy, and this is caused by consistent underestimation of the
      effective Born radii in the protein-ligand complex. The explicit solvent LIE
      calculations and LIE-PB, with our standard parametrization, reproduce absolute
      experimental binding free energies with an average unsigned error of 0.5 and 0.7
      kcal/mol, respectively. The LIE-GB method, however, requires a constant offset to
      approach the same level of accuracy.

PMID- 16800514
TI  - Comparing the morphology and phase diagram of H-shaped ABC block copolymers and
      linear ABC block copolymers.
AB  - By using a combinatorial screening method based on the self-consistent field
      theory (SCFT) for polymers, we have investigated the morphology of H-shaped ABC
      block copolymers (A2BC2) and compared them with those of the linear ABC block
      copolymers. By changing the ratios of the volume fractions of two A arms and two
      C arms, one can obtain block copolymers with different architectures ranging from
      linear block copolymer to H-shaped block copolymer. By systematically varying the
      volume fractions of block A, B, and C, the triangle phase diagrams of the H
      shaped ABC block copolymer with equal interactions among the three species are
      constructed. In this study, we find four different morphologies (lamellar phase
      (LAM), hexagonal lattice phase (HEX), core-shell hexagonal lattice phase (CSH),
      and two interpenetrating tetragonal lattice (TET2)). Furthermore, the order-order
      transitions driven by architectural change are discussed.

PMID- 16800515
TI  - Monte Carlo simulation of cisplatin molecule in aqueous solution.
AB  - The Lennard-Jones (12-6) parameters were obtained for all atoms of cisplatin
      molecule using the ab initio quantum mechanical potential energy surface for the
      water-cisplatin interaction as reference data. The parameters found were
      (epsilon/kcal.mol(-1) and sigma/angstroms) 1.0550, 3.6590 (Pt); 0.0381, 4.6272
      (Cl); 0.0455, 3.3783 (N); and 0.0185, 0.0936 (H) and provided very good results
      for the description of the aqueous solution of cisplatin through Monte Carlo
      simulation. From statistical analysis of solute-solvent interactions, we observed
      that the NH3 groups are involved in 53% of the calculated hydrogen bonds with a
      significant contribution from chlorides (41%) and only 6% involving the Pt
      center. This is in agreement with the expected behavior for such molecules. Two
      hydration shells with 22 and 81 water molecules, respectively, centered around
      4.6 and 7.3 angstroms were found from the center of mass pair correlation
      function analysis. The cisplatin atomic Lennard-Jones parameters are reported for
      the first time, and they might be useful for studying the structure, properties,
      and processes of cisplatin-like molecules in aqueous solution, including
      explicitly the solvent effect.

PMID- 16800516
TI  - Liquid structure of the ionic liquid 1,3-dimethylimidazolium
      bis[(trifluoromethyl)sulfonyl]amide.
AB  - Neutron diffraction has been used to determine the liquid structure of 1,3
      dimethylimidazolium bis[(trifluoromethyl)sulfonyl]amide ([dmim][NTf2]).
      Significantly smaller charge ordering is found in this liquid compared with
      analogous chloride and hexafluorophosphate salts due to the diffuse charge
      density and size of the [NTf2]- anion. This is manifested in a much larger cation
      cation and cation-anion separation and an overlap of the cation-cation and cation
      anion shells. Comparison of the liquid structure with the crystal structure
      reported by Holbrey et al. (Dalton Trans. 2004, 2267) indicates little
      correlation, for example, the [NTf2]- anion adopts a trans orientation
      predominantly in the liquid whereas a cis orientation is found in the solid
      phase.

PMID- 16800517
TI  - New force field for molecular simulation of guanidinium-based ionic liquids.
AB  - An all-atom force field was proposed for a new class of room temperature ionic
      liquids (RTILs), N,N,N',N'-tetramethylguanidinium (TMG) RTILs. The model is based
      on the AMBER force field with modifications on several parameters. The
      refinements include (1) fitting the vibration frequencies for obtaining force
      coefficients of bonds and angles against the data obtained by ab initio
      calculations and/or by experiments and (2) fitting the torsion energy profiles of
      dihedral angles for obtaining torsion parameters against the data obtained by ab
      initio calculations. To validate the force field, molecular dynamics (MD)
      simulations at different temperatures were performed for five kinds of RTILs,
      where TMG acts as a cation and formate, lactate, perchlorate, trifluoroacetate,
      and trifluoromethylsulfonate act as anions. The predicted densities were in good
      agreement with the experimental data. Radial distribution functions (RDFs) and
      spatial distribution functions (SDFs) were investigated to depict the microscopic
      structures of the RTILs.

PMID- 16800518
TI  - Existence of a size-dependent diffusivity maximum for uncharged solutes in water
      and its implications.
AB  - Recent studies suggest that there exists a size-dependent diffusivity maximum in
      binary mixtures interacting via Lennard-Jones potential when the size of one of
      the two components is varied (Ghorai, P. K.; Yashonath, S. J. Phys. Chem., 2005,
      109, 5824). We discuss in the present paper the importance of the existence of a
      size-dependent maximum for an uncharged solute in liquid or amorphous solid water
      and its relation to the ionic conductivity maximum in water. We report molecular
      dynamics investigations into the size dependence of the self-diffusivity, D, of
      the uncharged solutes in water at low temperatures (30 K) with immobile as well
      as mobile water. We find that a maximum in self-diffusivity exists as a function
      of the size of solute diffusing within water at low temperatures but not at high
      temperatures. This is due to the relatively weak interactions between the solute
      and the water compared to the kinetic energy at room temperature. Previously, we
      have shown that a similar maximum exists for guests sorbed in zeolites and is
      known as the levitation effect (LE). Thus, it appears that the existence of a
      size-dependent maximum is universal and extends from zeolites to simple liquids
      to solvents of polyatomic species. We examine the implications of this for the
      size-dependent maximum in ionic conductivity in polar solvents known for over a
      hundred years. These results support the view that the size-dependent maximum
      seen for ions in water has its origin in the LE (see Ghorai, P. Kr.; Yashonath,
      S.; Lynden-Bell, R. M. J. Phys. Chem. 2005, 109, 8120).

PMID- 16800519
TI  - The Kauzmann paradox at constant volume.
AB  - The entropy of o-terphenyl in the liquid and crystalline state heated at constant
      volume in the range 250-310 K is calculated from calorimetric data at a pressure
      of 0.1 MPa and equation of state data. The specific heat is found to fit the same
      functional form as that at 0.1 MPa and leads to a vanishing of the excess entropy
      at essentially the same Kauzmann temperature as that under isobaric conditions.
      This adds confirmation to the significance of the Kauzmann extrapolation and
      contradicts the expectation that constant volume heating would show qualitatively
      different behavior from isobaric heating.

PMID- 16800520
TI  - Low-temperature vapor-liquid equilibria from parallelized molecular dynamics
      simulations. Application to 1- and 2-methylnaphthalene.
AB  - A parallelized sampling version of the Gibbs Ensemble (Mol. Phys. 2000, 98, 1887)
      has been implemented to predict low-temperature vapor-liquid equilibria of 1- and
      2-methylnaphthalene modeled by anisotropic united atom potentials. The simulation
      were performed at the low temperature of 364.2 K at which common direct
      simulation methods fail due to particle transfer problems. The simulation results
      are compared with published results obtained from the Gibbs-Duhem integration
      method and with experimental data. Both methods are compared and discussed in
      terms of computational efficiency and with respect to their future use at other
      thermodynamic conditions.

PMID- 16800521
TI  - Effect of NaCl on the self-aggregation of n-octyl beta-D-thioglucopyranoside in
      aqueous medium.
AB  - This report investigates the effect of sodium chloride (NaCl) on the
      micellization, surface activity, and the evolution in the shape and size of n
      octyl beta-D-thioglucopyranoside (OTG) aggregates. By using surface tension
      measurements, information was obtained on both changes in the critical micelle
      concentration and adsorption behavior in the air-liquid interface with the
      electrolyte concentration. These data were used to obtain the thermodynamic
      properties of micellization along with the corresponding adsorption parameters in
      the air-liquid interface. From extended static and dynamic light scattering
      measurements, the micelle molecular weight, the mean aggregation number, and the
      second virial coefficient, the apparent diffusion coefficient and the mean
      hydrodynamic radius of micelles in a range of NaCl concentrations were obtained.
      The light scattering data have shown that when the surfactant concentration is
      lower to 4.5 g/L, only spherical micelles are formed. However, an increase in the
      surfactant concentration induces an increase in micellar size, suggesting a
      rodlike growth of the micelles. This deviation of micelle geometry from spherical
      to rodlike is supported both by the ratio between the hydrodynamic radius and the
      radius of gyration and by the angular dependence of light scattering. On the
      other hand, the studies performed in the presence of high NaCl concentration (0.2
      and 0.5 M) provide strong support for the view that the micelles may overlap
      together to form an entangled network above certain crossover concentration.

PMID- 16800522
TI  - Two-component system CCl4 + (CH3)3CBr: extrema in equilibria involving
      orientationally disordered phases.
AB  - Phase equilibria involving orientationally disordered (OD) and liquid phases of
      the two-component system between carbon tetrachloride (CCl4) and 2-methyl-2
      bromomethane ((CH3)3CBr) have been determined by means of X-ray powder
      diffraction and thermal analysis techniques from 210 K up to the liquid state.
      The isomorphism relation between the OD stable face-centered cubic (FCC) phase of
      (CH3)3CBr and the metastable FCC phase of CCl4 has been demonstrated throughout
      the continuous evolution of the lattice parameters and the existence of the two
      phase equilibrium [FCC + L] for the whole range of composition, despite the
      monotropy of the FCC phase for the CCl4 component with respect to its OD
      rhombohedral (R) stable phase. A continuous series of OD R mixed crystals is
      found, which confirms the R lattice symmetry of the OD phase II of (CH3)3CBr, for
      which the crystallographic results have been long-time misinterpreted. X-ray
      patterns of such a phase were indexed according to the recent single-crystal
      results obtained by Rudman (Rudman, R. J. Mol. Struct. 2001, 569, 157). In
      addition, some experimental evidences are given to confirm the number of
      molecules per unit cell (Z = 21). The thermodynamic assessment reproduces
      coherently the phase diagram for the stable [R + L] and [R + FCC] two-phase
      equilibria as well as for the partially metastable [FCC + L] two-phase
      equilibrium and provides a set of data for the thermodynamic properties of
      nonexperimentally available phase transitions of pure components. Surprisingly,
      the phase equilibrium involving R and FCC OD phases appears as one of the very
      few showing a solid-solid equilibrium with two extremes.

PMID- 16800523
TI  - Confusing cause and effect: energy-entropy compensation in the preferential
      solvation of a nonpolar solute in dimethyl sulfoxide/water mixtures.
AB  - We performed molecular simulations to analyze the thermodynamics of methane
      solvation in dimethyl sulfoxide (DMSO)/water mixtures (298 K, 1 atm). Two
      contributions to the interaction thermodynamics are studied separately: (i) the
      introduction of solute-solvent interactions (primary contribution) and (ii) the
      solute-induced disruption of cohesive solvent-solvent interactions (secondary
      contribution). The energy and entropy changes of the secondary contribution
      always exactly cancel in the free energy (energy-entropy compensation), hence
      only the primary contribution is important for understanding changes of the free
      energy. We analyze the physical significance of the solute-solvent energy and
      solute-solvent entropy associated with the primary contribution and discuss how
      to obtain these quantities from experiments combining solvation thermodynamic and
      solvent equation of state data. We show that the secondary contribution dominates
      changes in the methane solvation entropy and enthalpy: below 30 mol % DMSO in the
      mixture, methane, because of more favorable dispersion interactions with DMSO
      molecules, preferentially attracts DMSO molecules, which, in response, release
      water molecules into the bulk, causing an increase in the entropy. This large
      energy-entropy compensating process easily causes a confusion in the cause for
      and the effect of preferred methane-DMSO interactions. Methane-DMSO dispersion
      interactions are the cause, and the entropy change is the effect. Procedures that
      infer thermodynamic driving forces from analyses of the solvation entropies and
      enthalpies should therefore be used with caution.

PMID- 16800524
TI  - Inter- and intraconfigurational transitions of Nd3+ in hexafluoroelpasolite
      lattices.
AB  - Excitation of the 4f3 ion Nd3+ in hexafluoroelpasolite lattices by synchrotron
      radiation of wavelength approximately 185 nm leads to fast 4f(2)5d --> 4f3
      emission below 52,630 cm(-1) and slower 4f3 --> 4f3 emission from the luminescent
      states (4)F(3/2) gamma8u (11 524 cm(-1)) and 2G2(9/2) gamma8u (approximately
      47,500 cm(-1)). The near-infrared emission is well-resolved, and a clear
      interpretation of the 4I(9/2) crystal field levels and of the one-phonon vibronic
      sideband is given. The excitation spectrum of the 2G2(9/2) emission enables
      clarification of the structure of the 4f(2)5d configuration (which extends from
      approximately 52,000 to 128,000 cm(-1)). Detailed energy level and intensity
      calculations have been performed, which provide simulations of the d-f emission
      and the f-d excitation spectra in good agreement with experiment. It is
      interesting that although the 4f3 2G2(9/2) gamma8u --> 4f3 4I(J) transitions are
      very weak in intensity compared with transitions terminating upon higher
      multiplet terms, most of the 4f(2)5d (3H) 4I(9/2) gamma8g --> 4f3 emission
      intensity resides in the transitions to 4I(J).

PMID- 16800525
TI  - Hydrophobic and electrostatic interactions in the adsorption of fibronectin at
      maleic acid copolymer films.
AB  - Adsorption and desorption of fibronectin (FN) were investigated at thin films of
      alternating maleic acid copolymers with octadecene (POMA) and with propene
      (PPMA). The hydrophobicity and charge density of the polymers were modulated by
      the choice of the comonomer. In consequence, the dominant forces between the
      substrate and the protein were specified as hydrophobic interaction for POMA and
      electrostatic interaction for PPMA. The adsorption kinetics were investigated in
      situ as variations of the optical thickness, adsorbed mass, and viscoelastic
      properties (detected by reflectometric interference spectroscopy and quartz
      crystal microbalance technique, respectively) while alterations of the
      electrosurface properties were derived from surface conductivity data and
      isoelectric points (by streaming potential/current measurements using a microslit
      electrokinetic setup). The results demonstrate that the interfacial mode of
      adsorbed FN depends on the predominant interactions: large amounts of FN were
      tightly bound to POMA by hydrophobic interactions. In contrast, FN adsorbed on
      PPMA was concluded to attain an unfolded structure allowing for the
      "electrostatic matching" of positively charged residues on FN with the maleic
      acid groups. This conclusion was supported by the acidic IEP of 3.2 found for FN
      on PPMA and a significant reduction of the surface conductivity of the FN-covered
      polymer film, whereas FN on POMA showed an IEP of 4.2 (close to the intrinsic IEP
      of FN), indicating a stochastic orientation of the adsorbed protein.

PMID- 16800526
TI  - Toward absolute density of states calculations for proteins.
AB  - The density of states (DOS), which gives the number of conformations with a
      particular energy E, is a prerequisite in computing most thermodynamic quantities
      and in elucidating important biological processes such as the mechanism of
      protein folding. However, current methods for computing DOS of large systems such
      as proteins generally yield only the ratios of microstate counts for different
      energies, which could yield absolute conformation counts if the total number of
      conformations in phase space is known, thus motivating this work. Here, the total
      number of energy minima of 50-mer polyalanine, whose size corresponds to
      naturally occurring small proteins, was estimated under an all-atom potential
      energy function based on the cumulative distribution function (CDF) of
      conformational differences to be approximately 10(38). This estimate can place
      any DOS function, such as the Gaussian DOS distribution in the random energy
      model, on an absolute scale. Comparing the absolute conformational counts from a
      Gaussian DOS function with those from the CDF derived from quenched molecular
      dynamics ensembles shows that the former are far greater than the latter,
      indicating far fewer low-energy minima actually exist. In addition to showing how
      CDF and relative DOS calculations can yield absolute DOS for a discrete system,
      we also show how they can yield absolute DOS for continuous variable systems to a
      specified atomic variance. In the context of protein folding, knowing this phase
      space "volume" of conformations in a DOS function, as well as characteristic
      transition times, constrains the set of possible folding mechanisms.

PMID- 16800527
TI  - Polymorphic behavior in protein-surfactant mixtures: the water-bovine serum
      albumin-sodium taurodeoxycholate system.
AB  - Mixtures containing water, bovine serum albumin (BSA), and sodium
      taurodeoxycholate (NaTDC), a component of the bile in mammals, have been
      investigated in a wide range of composition and pH. Depending on the
      concentration of both solutes and the pH, solutions, precipitates, and gels are
      formed. Under spontaneous pH conditions, the transport properties in dilute
      solutions indicate the occurrence of significant interactions between BSA and the
      surfactant. Conversely, acidic media favor the formation of nonsoluble protein
      surfactant complexes, with subsequent precipitation. The nucleation kinetics of
      the protein-surfactant complexes in solid form and the related precipitation
      processes can be slow or fast, depending on the overall solute content and the
      mole ratio. At high concentrations, a gel, extending on both sides of the charge
      neutralization line, and two-phase regions are observed. Gels shrink in open air
      and swell in the presence of excess water. Depending on concentration and
      temperature, the gels transform from an essentially liquidlike behavior to that
      peculiar to true gels (when G' > or = G''). The thermal gelation threshold, the
      temperature above which G' > or = G'', depends on BSA and NaTDC content and is
      concomitant to moderate heat effects, inferred by differential scanning
      calorimetry (DSC). The above data also indicate that the protein thermal
      denaturation in the gel is shifted to higher temperatures compared to water. Such
      a stabilizing effect is presumably related to the occurrence of both
      electrostatic and hydrophobic interactions with NaTDC. Water self-diffusion in
      the gels is slightly slower than that in the bulk and poorly sensitive to
      composition: it is about 65% the value of neat H2O in a wide concentration range,
      irrespective of the BSA, or NaTDC, concentration. A peculiar behavior is also
      observed in 23Na longitudinal and transverse relaxation rates. The T1 and T2
      values, measured at 105.75 MHz on BSA-NaTDC gels, indicate that the motions
      determining the NMR relaxation of the sodium ions in the hydration layer of the
      protein-surfactant aggregates are not slow, having frequencies comparable with
      the Larmor one. The above properties, especially the rheological and the
      spectroscopic ones, are important for understanding the behavior of gels based on
      protein-surfactant mixtures.

PMID- 16800528
TI  - Coarse-grained modeling of proline rich protein 1 (PRP-1) in bulk solution and
      adsorbed to a negatively charged surface.
AB  - Structural properties of the acidic proline rich protein PRP-1 of salivary origin
      in bulk solution and adsorbed onto a negatively charged surface have been studied
      by Monte Carlo simulations. A simple model system with focus on electrostatic
      interactions and short-ranged attractions among the uncharged amino acids has
      been used. In addition to PRP-1, some mutants were considered to assess the role
      of the interactions in the systems. Contrary to polyelectrolytes, the protein has
      a compact structure in salt-free bulk solutions, whereas at high salt
      concentration the protein becomes more extended. The protein adsorbs to a
      negatively charged surface, although its net charge is negative. The adsorbed
      protein displays an extended structure, which becomes more compact upon addition
      of salt. Hence, the conformational response upon salt addition in the adsorbed
      state is the opposite as compared to that in bulk solution. The conformational
      behavior of PRP-1 in bulk solution and at charged surfaces as well as its
      propensity to adsorb to surfaces with the same net charge are rationalized by the
      block polyampholytic character of the protein. The presence of a triad of
      positively charged amino acids in the C-terminal was found to be important for
      the adsorption of the protein.

PMID- 16800529
TI  - Theoretical study of volume changes accompanying xenon-lysozyme binding:
      implications for the molecular mechanism of pressure reversal of anesthesia.
AB  - The change in partial molar volume (PMV) accompanying the xenon-lysozyme binding
      was investigated for elucidating the molecular mechanism of the pressure reversal
      of general anesthesia, using the three-dimensional reference interaction site
      model theory of molecular solvation. An increase of the PMV from xenon binding to
      the substrate binding site of lysozyme was found, and the binding is suppressed
      by pressure, while the internal site binding did not change the PMV. The PMV
      change was analyzed by decomposing it into several contributions from geometry
      and hydration. We also analyzed the hydration change due to the binding. From the
      results, we draw a molecular picture of the PMV change accompanying xenon
      lysozyme binding, which gives a possible mechanism of pressure reversal of
      anesthesia.

PMID- 16800530
TI  - Functionally relevant electric-field induced perturbations of the prosthetic
      group of yeast ferrocytochrome c mutants obtained from a vibronic analysis of low
      temperature absorption spectra.
AB  - We have measured the low temperature (T = 20 K) absorption spectra of the N52A,
      N52V, N52I, Y67F, and N52AY67F mutants of ferrous Saccharomyces cerevisiae
      (baker's yeast) cytochrome c. All the bands in the Q0- and Q(v)-band region are
      split, and the intensity distributions among the split bands are highly
      asymmetric. The spectra were analyzed by a decomposition into Voigtian profiles.
      The spectral parameters thus obtained were further analyzed in terms of the
      vibronic coupling model of Schweitzer-Stenner and Bigman (Schweitzer-Stenner, R.;
      Bigman, D. J. Phys. Chem. B 2001, 7064-7073) to identify parameters related to
      electronic and vibronic perturbations of the heme macrocycle. We report that the
      electronic perturbation is of B(1g) symmetry and reflects the heterogeneity of
      the electric field at the heme, that is, the difference between the gradients
      along the perpendicular N-Fe-N axis of the heme core. We found that all the
      investigated mutations substantially increase this electronic perturbation, so
      that the spectral properties become similar to those of horse heart cytochrome c.
      Moreover, the electronic perturbation was found to correlate nonlinearly with the
      enthalpy changes associated with the reduction of the heme iron. Group
      theoretical arguments are invoked to propose a simple model which explains how a
      perturbation of the obtained symmetry can stabilize the reduced state of the heme
      iron. Finally, vibronic coupling parameters obtained from the analysis of the
      Q(v)-band region suggest that the investigated mutations decrease the nonplanar
      deformations of the heme group. This finding was reproduced by a normal mode
      structural decomposition (NSD) analysis of the N52V and N52VY67F heme
      conformations obtained from a 1 ns molecular dynamics simulation. We argue that
      the reduced nonplanarity contributes to the stabilization of the reduced state.

PMID- 16800531
TI  - Improved density functional theory/electrostatic calculation of the His291
      protonation state in cytochrome C oxidase: self-consistent charges for solvation
      energy calculation.
AB  - The protonation state of His291 in cytochrome c oxidase (CcO), a ligand to the
      Cu(B) center of the enzyme, has been recently studied in this group by using
      combined density functional theory (DFT)/electrostatic (QM/MM) calculations. On
      the basis of these calculations, a model of the proton pumping mechanism of CcO
      has been proposed. Due to certain technical difficulties, the procedure used in
      the previous calculation to find partial atomic charges of the QM system for the
      solvation energy evaluation was not entirely satisfactory; i.e., it was not self
      consistent. Here, we describe a procedure that resolves the problem and report on
      the improved calculations of the protonation state of the His residue. The new
      procedure fits the protein and reaction field potentials in the region of the QM
      system with artificial point charges placed on a surface of a sphere surrounding
      the QM system and a few charges inside the sphere and allows one to perform DFT
      calculations that involve an inhomogeneous dielectric environment in a self
      consistent way. The procedure improves the accuracy of calculations in comparison
      with previous work. The improved results show, however, that although the
      absolute energies change significantly the relative energies of the protonated
      and deprotonated states of His291 remain close to the previously reported ones
      and therefore do not change significantly the pK(a) values reported earlier.
      Therefore, our new improved calculations support for the proposed His291 model of
      the CcO pump.

PMID- 16800532
TI  - Photosensitization of nanostructured TiO2 with WS2 quantum sheets.
AB  - Porous, nanostructured sol gel TiO2 (100 nm) has been sensitized with WS2 quantum
      sheets (approximately 5 nm) with the help of chemical bath deposition. The
      absorber has been characterized with help of energy dispersive X-ray (EDX),
      transmission electron microscopy (TEM), scanning electron microscopy (SEM), Raman
      spectroscopy, and light absorption measurements. The photosensitization was
      confirmed via electrochemical measurements. The surface of TiO2 has been modified
      by a thin Al2O3 film, which significantly enhanced the photocurrent density to
      0.4-0.7 mA/cm2. Moire patterns suggest that the S-W-S layers of WS2 are not
      perfectly aligned in the direction of the c-axis, emphasizing the role of lateral
      electron transfer, which is also evidenced by surface passivation experiments.
      With WS2, a new, cheap, environmentally friendly, and stable absorber material
      for the sensitization of wide band gap nanomaterials has been introduced.

PMID- 16800533
TI  - Transparent perfluoropolyethers for vacuum ultraviolet applications.
AB  - After a broad scouting based on quantum chemical calculations, optical absorption
      measurements in the vacuum ultraviolet (VUV) wavelength region between 140 and
      190 nm were performed on a narrower series of commercial and experimental
      liquids. By elimination of sources of external contamination, mainly due to
      atmospheric gases, the analysis of the contributions to the absorption related to
      the backbone structure and to the chain end composition allowed the synthesis of
      a novel family of linear perfluoropolyethers (PFPEs) with optical absorbance at
      157 nm between 0.3 and 0.6 cm(-1) in a broad range of compositions and molecular
      weights. The dependence of the optical threshold on the PFPE composition
      demonstrates that -OCF2- is the most transparent segmental unit in the VUV
      region.

PMID- 16800534
TI  - Evidence in support of levitation effect as the reason for size dependence of
      ionic conductivity in water: a molecular dynamics simulation.
AB  - We report extensive molecular dynamics simulations of (i) model ions in water at
      high concentrations as a function of the size and charge of the ion as well as
      (ii) realistic simulation of Cl- and Br- ions at low concentrations in water at
      room temperature. We also analyze existing experimental data in light of the
      results obtained here. The halide ion simulations have been carried out using the
      interaction potentials of Koneshan et al. (J. Phys. Chem. B 1998, 102, 4193). We
      compute structural and dynamical properties of ions in water and explore their
      variation with size and charge of the ion. We find that ions of certain
      intermediate sizes exhibit a maximum in self-diffusivity in agreement with
      previous experimental measurements and computer simulations. We analyze molecular
      dynamics trajectories in light of the previous understanding of the levitation
      effect (LE) and the recent suggestion that ionic conductivity has its origin in
      LE (J. Phys. Chem. B 2005, 109, 8120). We report the distribution of void and
      neck radii that exist amidst water. Our analysis suggests that the ion with
      maximum self-diffusivity is characterized by a lower activation energy and a
      single-exponential decay of F(s)(k,t). The behavior of these and other related
      quantities of the ion with maximum self-diffusivity are characteristic of the
      anomalous regime of the LE. The simulation results of Br- and Cl- ions in water
      also yield results in agreement with the predictions of LE. A plot of
      experimental conductivity data in the literature for alkali ions in water by Kay
      and Evans (J. Phys. Chem. 1966, 70, 2325) also yields a lower activation energy
      for the ion with maximum conductivity in excellent agreement with the LE. To the
      best of our knowledge, none of the existing theories predict a lower activation
      energy for the ion with maximum conductivity.

PMID- 16800535
TI  - Peculiar properties of water as solute.
AB  - Water has been investigated for a long time as the most important solvent; the
      peculiar behavior of water as solute has been studied in binary mixtures with
      organic solvents, mainly exploring the whole phase diagram. In this Article, we
      studied the behavior of water in binary mixtures with propylene carbonate in the
      phase diagram region where water acts as a solute as a function of the water
      molar fraction X(water). Surface tension measurements, differential scanning
      calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) have been
      used to investigate the state of water molecules and hydrogen bonds when water is
      to be considered a solute instead of a solvent, and peculiar and interesting
      properties were discovered. The interaction of water molecules among themselves
      and between water and propylene carbonate has been shown to be dependent on the
      water concentration in the mixtures. All of the measured properties showed a
      break at X(water) approximately 0.15-0.20 similar to the break due to the
      critical micellar concentration in surfactant solutions. In particular, from the
      FTIR spectra, it was possible to deduce that at this concentration water has a
      transition from pure solute ("multimers" solvated by PC) to cosolvent
      ("intermediate" and "network" water).

PMID- 16800536
TI  - Product and pulse radiolysis studies on radical-ion splitting of N(1)-C(5')
      linked dimer hydrates of 5-substituted uracils by one-electron reduction in
      anoxic aqueous solution.
AB  - Steady-state gamma-radiolysis, pulse radiolysis, and cyclic voltammetry have been
      performed to identify the mechanism by which N(1)-C(5')-linked homodimer hydrates
      [1-(6'-hydroxy-5',6'-dihydrothymin-5'-yl)thymine (2a) and [1-(5'-fluoro-6'
      hydroxy-5',6'-dihydrouracil-5'-yl)-5-fluorouracil (2b)], N(1)-C(6')-linked dimer
      hydrate [1-(5'-hydroxy-5',6'-dihydrothymin-6'-yl)thymine (3a)], and N(1)-C(5')
      linked heterodimer hydrate [1-(6'-hydroxy-5',6'-dihydrothymin-5'-yl)-5
      fluorouracil (2ba)] undergo radiolytic reductive splitting to regenerate the
      parent monomers in anoxic aqueous solution. Radiolytic reductions of the thymine
      homodimer hydrates 2a and 3a by hydrated electrons (e(aq)-) regenerated the
      parent thymine (1a) almost quantitatively, while the 5-fluorouracil homodimer
      hydrates cis-2b and trans-2b afforded 1-(uracil-5'-yl)-5-fluorouracil efficiently
      along with a small amount of the parent 5-fluorouracil (1b). In contrast to 2b,
      the heterodimer hydrate analogue 2ba with noneliminating 5'-methyl substituent
      releases 5-fluorouracil 1b almost quantitatively in the radiolytic reduction. The
      pulse radiolysis studies suggested that the electron adducts are produced
      primarily at the thymine and 5-fluorouracil structural unit in the dimer hydrates
      2a,b, respectively, in which the resulting dimer hydrate radical anion of 2b (2b*
      ) was more stable than that of 2a (2a*-). As characterized by pulse radiolysis
      and cyclic voltammetry, the 5-fluorouracil homodimer hydrate 2b bearing F
      substituent at C(5') undergoes one-electron reduction to eliminate exclusively
      fluoride ion along with the formation of dimer hydrate C(5') radical (2b(-F)*)
      with oxidizing property. The formation of a possible dimer hydrate radical
      intermediate 2b(-F)* was also supported by the effect of amines as the reducing
      additives on the yields of 1b and 4b in the radiolytic reduction of 2b.

PMID- 16800537
TI  - Reversible formation of glassy water in slowly cooling diluted drops.
AB  - This letter presents experimental results obtained with a differential scanning
      calorimeter (DSC), which indicate that glassy water can be produced reversibly
      within slowly cooling diluted H2SO4/H2O drops.

PMID- 16800538
TI  - Dianhydride-amine hydrogen bonded perylene tetracarboxylic dianhydride and
      tetraaminobenzene rows.
AB  - We have investigated the coadsorption of perylene tetracarboxylic dianhydride
      (PTCDA) and tetraaminobenzene (TAB) on the Ag/Si(111)-square root(3) x square
      root(3) R30 degree surface using scanning tunneling microscopy. At room
      temperature, PTCDA islands with square and herringbone ordering are formed which,
      on exposure to TAB, are converted into an intermixed phase in which PTCDA and TAB
      form alternating rows. From our images, we determine the relative placement of
      TAB and PTCDA molecules and conclude that the row structure is stabilized by
      hydrogen bonding between dianhydride and diamine groups. We confirm that this
      hydrogen bonding junction is stable using ab initio calculations and show that
      the proposed geometry is consistent with calculated intermolecular dimensions.

PMID- 16800539
TI  - On the origin of a permanent dipole moment in nanocrystals with a cubic crystal
      lattice: effects of truncation, stabilizers, and medium for CdS tetrahedral
      homologues.
AB  - A large anomalous dipole moment has previously been reported for nanocrystals
      with a cubic crystal lattice. By considering truncations of a regular tetrahedral
      CdS nanocrystal, the hypothesis that shape asymmetry is responsible for the
      observed dipole moment was tested and verified. The location and degree of the
      truncations were systematically varied, and corresponding dipole moments were
      calculated by using a PM3 semiempirical quantum mechanical algorithm. The
      calculated dipole moment of 50-100 D is in good agreement with a variety of
      experimental data. This approach also affords simple evaluation of the potential
      effect of the media for aqueous dispersions of nanocrystals. The substitution of
      the truncated corner(s) by molecules of H2O typically results in a substantial
      increase of the dipole moment, and often, in the reversal of its direction. The
      molecular modeling approach presented here is suitable for detailed theoretical
      studies of the dipole moments of II-VI and other nanoparticles and interparticle
      interactions in fluids. The data obtained from these calculations can be the
      starting point for modeling of agglomeration and self-organization behavior of
      large nanoparticle ensembles.

PMID- 16800540
TI  - Kinetic stabilization of growing gold clusters by passivation with thiolates.
AB  - Small gold clusters (<1 nm), protected by monolayers of glutathione, N-(2
      mercaptopropionyl)glycine, or mercaptosuccinic acid, were prepared by reducing
      the corresponding Au(I)-thiolate polymers and were fractionated by size using
      polyacrylamide gel electrophoresis (PAGE). Mass analysis of the fractionated
      clusters revealed that their core sizes varied with the molecular structures of
      the thiolates. This finding indicates that the reduction of the Au(I)-thiolate
      polymers yields small clusters whose growth is kinetically hindered by
      passivation with thiolates. Optical spectra of the clusters with identical
      compositions exhibited different profiles depending on the thiolate molecular
      structures. This observation implies that deformation of the underlying gold
      cores is induced by interligand interactions.

PMID- 16800541
TI  - Hydrophobic hydration in cyclodextrin complexation.
AB  - We report temperature-dependent acoustic and densimetric data on changes in
      volume, expansibility, and adiabatic compressibility accompanying the binding of
      1-adamantanecarboxylic acid (AD) to beta-cyclodextrin (beta-CD). We interpret our
      volumetric results in terms of hydration. Based on our compressibility and
      expansibility data, we estimate that, at 25 degrees C, the binding of AD to beta
      CD is accompanied by displacement of 20 to 25 water molecules from the hydration
      shells of the two interacting species. Comparison of the temperature-dependent
      compressibility changes accompanying the binding of AD to beta-CD with the
      compressibility contribution of aliphatic groups suggests that displaced water
      molecules predominantly come from the hydrophobic loci of AD and beta-CD. Thus,
      we conclude that hydrophobic interactions play a major role in stabilizing the AD
      beta-CD complex. Our estimate of the number of water molecules released to the
      bulk is consistent with structural considerations. There is also good agreement
      between our volumetric data and osmotic stress results reported by Harries et al.
      (Harries, D.; Rau, D. C.; Parsegian, V. A. J. Am. Chem. Soc. 2005, 127, 2184).
      This observation is consistent with the picture in which the two techniques probe
      the same population of water molecules solvating AD and beta-CD.

PMID- 16800542
TI  - Supramolecular hydrogels induced rapidly by inclusion complexation of
      poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) block
      copolymers with alpha-cyclodextrin in aqueous solutions.
AB  - On the basis of the synthesis of water-soluble poly(epsilon-caprolactone)
      poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) block copolymers,
      the supramolecular hydrogels were fabricated rapidly in aqueous solutions by
      their inclusion complexation with alpha-cyclodextrin. X-ray diffraction (XRD)
      analyses confirmed the supramolecular self-assemblies of alpha-cyclodextrin
      threaded onto amphiphilic PCL-PEG-PCL block copolymers. The resulting hydrogels
      display a high degree of elasticity, with the storage modulus (G') greater than
      the loss modulus (G'') over the entire range of frequency. Moreover, their
      viscosity greatly diminished as they were sheared. By controlling the molecular
      weight of the PEG component in the block copolymers and the content of the block
      copolymer, their rheological properties could be modulated. Such hydrogel
      materials have the potential to be used as tissue engineered scaffolds,
      biosensors in the human body, and carriers for controlled drug delivery.

PMID- 16800543
TI  - Nonlinear transmission of a tetrabrominated naphthalocyaninato indium chloride.
AB  - The axially substituted complex chloro indium(III) 2-tetrabromo-3-tetra-(3,5-di
      tert-butylphenyloxy)naphthalocyanine [Br4(tBu2PhO)4NcInCl (1); MW = 1996] has
      been synthesized for the first time, and its nonlinear transmission properties
      have been evaluated with the Z-scan technique in both open and closed aperture
      configurations at 532 nm for nanosecond pulsed radiation. The tetrabrominated
      complex 1 displayed a larger positive nonlinear absorption coefficient when
      compared to an analogous nonbrominated naphthalocyanine [(tBu2PhO)8NcInCl (2); MW
      = 2498]. The effect of the four Br atoms on the nonlinear optical behavior of 1
      is evaluated, discussed, and compared with the nonlinear optical behavior of 2.
      It is shown that the bromination of the naphthalocyanine ring considerably
      improves the limiting properties of such a system when high-intensity radiations
      are produced by nanosecond laser pulses at 532 nm.

PMID- 16800544
TI  - Theoretical insights on O2 and CO adsorption on neutral and positively charged
      gold clusters.
AB  - With the aim of understanding the elementary steps governing the oxidation of CO
      catalyzed by dispersed or supported gold nanoclusters, the adsorption of
      molecular species, such as O2 and CO, on model neutral and positively charged
      clusters (Au(n)(m+) n = 1, 9, and 13; m = 0, 1, and 3) has been studied using an
      ab initio approach. The computed structural and thermodynamic data related to the
      binding process show that molecular oxygen interacts better with neutral
      clusters, acting as an electron acceptor, while CO more strongly binds to
      positively charged species, thus acting as an electron donor.

PMID- 16800545
TI  - Surfactant-free hydrothermal synthesis of highly tetragonal barium titanate
      nanowires: a structural investigation.
AB  - Barium titanate nanowires synthesized with a surfactant-free hydrothermal method
      have been characterized by various techniques such as transmission electron
      microscopy (TEM), scanning electron microscopy (SEM), synchrotron X-ray
      diffraction, X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. The
      TEM and SEM analyses show the uniform cylindrical nanowires. The Rietveld
      refinement with synchrotron X-ray powder diffraction showed that the lattice
      parameters of cubic and tetragonal phases were a (= b = c) = 4.0134 A and a (= b)
      = 3.9998 A, c = 4.0303 A, respectively. The final weighted R-factor, R(wp), was
      6.75% and the goodness of fit indicator was 1.30. The mass fraction of tetragonal
      and cubic phases based on the refined scale factor for the two phases were 98.4%
      and 1.6%, respectively, which clearly show the nanowires are tetragonal. The XPS
      analysis has shown that as-obtained BaTiO3 nanowires were phase pure. The Raman
      spectra confirm the tetragonal phase of the BaTiO3 nanowires. The dielectric
      constant measurement shows the shift in the transition temperature (Tc = 105
      degrees C) compared to the bulk transition temperature (Tc = 132 degrees C). The
      dielectric constant at Tc was 174 measured at 1 kHz frequency.

PMID- 16800546
TI  - Photochemically generated stable cation radical of phenothiazine aggregates in
      mildly acid buffered solutions.
AB  - This work characterizes, for the first time, the photochemical behavior of the
      antipsychotic drugs thioridazine (TR), trifluoperazine (TFP), and fluphenazine
      (FP) influenced by the aggregation state of the molecules. Samples of monomeric
      and aggregated forms of phenothiazines were submitted to 20 min of irradiation at
      254 nm for intervals of 1, 5, 10, 15, 20, or 25 days. In high phenothiazine
      concentrations, the irradiation led to the appearance of absorbance bands in the
      visible region peaking at 633 nm for TR and 509 nm for FP and TFP. In the dark,
      at room temperature and at 4 degrees C, these bands disappeared, after
      approximately 15 and approximately 60 min, respectively, but reappeared after a
      new irradiation session. These visible bands were assigned to stable cation
      radicals that were characterized by direct EPR measurements and by flash
      photolysis. Photogenerated stable cation radicals in the phenothiazine aggregates
      at room temperature are formed probably due to the stacking of the thiazine
      phenyl moieties. For the monomeric forms of phenothiazines, the spectral changes
      observed during the irradiation suggested the formation of sulfoxide and
      hydroxylated derivates. Oxidized derivates were detected by mass spectrometry of
      the aggregated forms of phenothiazines (>100 microM) only in the samples
      irradiated for more than 20 days. In contrast, monomeric phenothiazines were
      totally converted to the oxidized forms after 20 min of irradiation. Surface
      tension measurements of phenothiazines revealed that, in concentrations above 100
      microM, the drugs formed aggregates. In the case of TR, small-angle X-ray
      scattering measurements indicated that this compound forms large lamellar-like
      aggregates in aqueous solutions.

PMID- 16800547
TI  - Phase behavior of monoglycerol fatty acid esters in nonpolar oils: reverse
      rodlike micelles at elevated temperatures.
AB  - We have studied nonaqueous phase behavior and self-assemblies of monoglycerol
      fatty acid esters having different alkyl chain lengths in different nonpolar
      oils, namely, liquid paraffin (LP 70), squalane, and squalene. At lower
      temperatures, oil and solid surfactants do not mix at all compositions of mixing.
      Upon an increase in the temperature of the surfactant system, the solid melts to
      give isotropic single or two-liquid phases, depending on the nature of the oil
      and the surfactant. All monolaurin/oil systems form an isotropic single-phase
      liquid, but with a decreasing alkyl chain length of surfactant, they become less
      lipophilic and immiscible in oils. As a result, a two-phase domain is observed in
      the oil rich region of all monocaprylin/oil systems over a wide range of
      concentrations. Judging from the phase diagrams, the surfactants are the least
      miscible with squalane, and the order of miscibility tendency is squalene > LP 70
      > squalane. With a further increase of temperature, the solubility of the
      surfactant in the oil increases, and the two-liquid phase transforms to an
      isotropic single phase. This phase transformation corresponds to the reverse of
      the cloud-point phenomenon observed in aqueous nonionic surfactant systems. Small
      angle X-ray scattering (SAXS) measurements show the presence of reversed rodlike
      micelles in the isotropic single phase, and the length of the aggregates
      decreases with increasing temperature and increasing alkyl chain length of the
      surfactant. These results indicate a rod-sphere transformation with increasing
      lipophilicity of the surfactant and confirms the validity of Ninham's penetration
      model in the reversed system. An addition of a small amount of water dramatically
      enhances the elongation of the reverse micelles. Increasing the surfactant
      concentration or changing the oil from squalene to LP 70 also increases the
      length of the rodlike aggregates.

PMID- 16800548
TI  - Quantitative model of electrochemical Ostwald ripening and its application to the
      time-dependent electrode potential of nanocrystalline metals.
AB  - The contact of a metastable nanocrystalline metal ensemble with a metal ion
      electrolyte leads to an electrochemical Ostwald ripening. The kinetics is modeled
      on the level of irreversible thermodynamics for the case that the rate is
      controlled by the electrode/electrolyte transfer resistance. In particular, the
      kinetic behavior of medium-sized particles and the time dependence of the
      electromotive force is investigated. Even though it is expressed in
      electrochemical terms (mixed potential), the modeling is also applicable to
      chemical Ostwald ripening as long as it is interfacially controlled. Under these
      conditions, the kinetics exhibits, even though not self-accelerating, strong
      similarities to selection dynamics, with the competition stemming from the
      cannibalistic nature of the process.

PMID- 16800549
TI  - Confinement effect in diffusion-controlled stepwise polymerization by Monte Carlo
      simulation.
AB  - Diffusion-controlled stepwise polymerization of a linear polymer confined in
      nanoscopic slits is simulated through a Monte Carlo approach. A noticeable
      influence of the confinement on the kinetics is found. The confinement modifies
      both the spatial pair distribution function and the diffusive properties of the
      polymers. As a consequence, the confined system can show either faster or slower
      reaction kinetics with respect to the bulk system, depending on the strength of
      intermolecular interactions. The predicted polydispersity of the polymer is in
      agreement with recent theories of diffusion-controlled stepwise polymerization,
      and can be slightly affected by the confinement.

PMID- 16800550
TI  - Shear modulated percolation in carbon nanotube composites.
AB  - A novel time-dependent percolation transition has been observed in sheared carbon
      nanotube (CNT) composites. At a fixed CNT filler loading, the electrical
      conductivities of CNT composites can change abruptly as much as 8 orders of
      magnitude as the shear processing time increases. Microstructure characterization
      shows that the CNTs have aligned along the shear flow direction, which leads to
      the dramatic increase of the percolation threshold and thereby the dramatic
      decreases of the electrical conductivities. Our results highlight the great
      importance of understanding the response of CNT dispersion states to the
      processing conditions.

PMID- 16800551
TI  - One-dimensional zigzag chains of Cs-: the structures and properties of Li+
      (cryptand[2.1.1])Cs- and Cs+ (cryptand[2.2.2])Cs-.
AB  - The crystal structure and properties of lithium (cryptand[2.1.1]) ceside, Li+
      (C211)Cs-, are reported. Li+ (C211)Cs- is the second ceside and third alkalide
      with a one-dimensional (1D) zigzag chain of alkali metal anions. The distance
      between adjacent Cs- anions, 6 A, is shorter than the sum of the van der Waals
      radii, 7 A. Optical, magic angle spinning NMR, two-probe alternating and direct
      current conductivity, and electron paramagnetic resonance measurements reveal
      unique physical properties that result from the overlap of adjacent Cs- wave
      functions in the chain structure. The properties of cesium (cryptand[2.2.2])
      ceside, Cs+ (C222)Cs-, were also studied to compare the effects of the subtle
      geometric changes between the two 1D zigzag chain structures. Li+ (C211)Cs- and
      Cs+ (C222)Cs- are both low-band-gap semiconductors with anisotropic
      reflectivities and large paramagnetic 133Cs NMR chemical shifts relative to Cs-
      (g). An electronic structure model consistent with the experimental data has sp2
      hybridized Cs- within the chain and sp-hybridized chain ends. Ab initio
      multiconfiguration self-consistent field calculations on the ceside trimer, Cs3(3
      ), support this model and indicate a net bonding interaction between nearest
      neighbors. The buildup of electron density between adjacent Cs- anions is
      visualized through an electron density difference map constructed by subtracting
      the density of three cesium atoms from the short Cs3(3-) fragment.

PMID- 16800552
TI  - Plasmon modes of nanosphere trimers and quadrumers.
AB  - Using the plasmon hybridization method, we investigate the plasmon frequencies
      and optical absorption spectra of symmetric configurations of nanosphere trimers
      and quadrumers. Plasmon hybridization allows us to express the fundamental
      plasmon modes of these multinanosphere systems as linear combinations of the
      plasmons of individual nanospheres in a manner analogous to molecular orbital
      theory. We show how group theory may be used to interpret the plasmon modes of
      each multiparticle system as specific structure-dependent symmetric combinations
      of the plasmon modes of the individual nanoparticles. We compare the optical
      absorption spectra calculated using plasmon hybridization with the spectra
      obtained using finite difference time domain simulations.

PMID- 16800553
TI  - Aqueous-organic phase-transfer of highly stable gold, silver, and platinum
      nanoparticles and new route for fabrication of gold nanofilms at the oil/water
      interface and on solid supports.
AB  - A simple but effective aqueous-organic phase-transfer method for gold, silver,
      and platinum nanoparticles was developed on the basis of the decrease of the
      PVP's solubility in water with the temperature increase. The present method is
      superior in the transfer efficiency of highly stable nanoparticles to the common
      phase-transfer methods. The gold, silver, and platinum nanoparticles transferred
      to the 1-butanol phase dispersed well, especially silver and platinum particles
      almost kept the previous particle size. Electrochemical synthesis of gold
      nanoparticles in an oil-water system was achieved by controlling the reaction
      temperature at 80 degrees C, which provides great conveniences for collecting
      metal particles at the oil/water interface and especially for fabricating dense
      metal nanoparticle films. A technique to fabricate gold nanofilms on solid
      supports was also established. The shapes and sizes of gold nanoparticles as the
      building blocks may be controllable through changing reaction conditions.

PMID- 16800554
TI  - Preparation and characterization of silver-poly(vinylidene fluoride)
      nanocomposites: formation of piezoelectric polymorph of poly(vinylidene
      fluoride).
AB  - In situ Ag nanoparticles are produced on reduction of Ag+ with N,N
      dimethylformamide in the presence of poly(vinylidene fluoride) (PVF2). The
      plasmon band transition is monitored with time in the reaction mixture for three
      sets of experiments by UV-vis spectroscopy. The plasmon band absorbance increases
      sigmoidally with log(time). Analysis of the data with the Avrami equation yields
      an exponent n value between 1.5 and 2.0, indicating two-dimensional nucleation
      with linear or diffusion controlled growth. The TEM study of the polymer
      nanocomposites (PNC) indicates both spherical and rodlike morphology for PNC0.5
      and PNC2.5 samples, whereas the PNC11 sample has spherical and agglomerated
      structures (the numerical number associated with PNC indicates percentage (w/w)
      of Ag in the nanocomposite). The WAXS and FTIR studies indicate the formation of
      piezoelectric beta-polymorphic PVF2 in the nanocomposites. The DSC study
      indicates some increase of the melting point and enthalpy of fusion of PVF2 in
      the nanocomposite, although with increase in Ag nanoparticle concentration the
      increase is smaller. The crystallization temperatures of PNCs also increased,
      indicating nucleating effect of Ag nanoparticles in the composite. In the TGA
      curves, the PNCs exhibit a three-step degradation process. The degradation
      temperatures of PNCs are lower than that of PVF2. The storage modulus data
      indicate a significant reinforcement of the mechanical property in the PNCs where
      also the reinforcement effect decreases with increasing nanoparticle
      concentration. Both the loss modulus and tan delta plots indicate two peaks; the
      lower temperature peak has been attributed for glass transition temperature,
      whereas the higher one has been attributed to a similar type relaxation process
      for the crystalline-amorphous interface. The increase in the glass transition is
      marginal for the PNCs, but the increase of later transition temperature is
      somewhat higher. The FTIR study shows that the dipolar interaction of the >CF2
      dipole with the surface charges of Ag nanoparticle stabilizes the nanoparticle in
      the nanocomposite.

PMID- 16800555
TI  - Linearly polarized emission of an organic semiconductor nanobelt.
AB  - Linearly polarized emission has been observed for the nanobelts fabricated from a
      perylene diimide molecule through both solution-based and surface-supported self
      assembling. The measurement of polarized emission was performed over single
      nanobelts with use of a near-field scanning optical microscope (NSOM) adapted
      with emission polarization (by putting a planar polarizer before the detector).
      Rotating the emission polarizer (from 0 degrees to 180 degrees) changed the
      emission intensity in a way depending on the relative angle between the long axis
      of the belt and the polarizer with a minimum of intensity detected at ca. 78
      degrees, which is indicative of the tilted stacking of molecules along the belt
      direction.

PMID- 16800556
TI  - Structural selection and amorphization of small Ni-Ti bimetallic clusters.
AB  - Classical molecular dynamics simulation is used for structural thermodynamic
      analysis of Ni-Ti bimetallic clusters. Experimental observation for the
      nanoclusters synthesized by the bioreduction method is used to consolidate the
      conclusion. The results demonstrate that Ni-Ti nanoclusters as small as 2-3 nm
      are not energetically favorable for common ordered geometrical arrangements such
      as cuboctahedron, decahedron, and icosahedron, though they can be synthesized
      experimentally. For the elemental distribution, Ni and Ti tend to aggregate
      separately. In the cases under study, eutectic-like and Ni-core/Ti-shell
      structures can keep their basic shape and elemental distribution during long
      periods of relaxation at room temperature. For other cases such as solid solution
      and Ti-core/Ni-shell, the structures amorphized and the elements tend to
      distribute uniformly even though they are at temperatures as low as room
      temperature. Experimental evidence was obtained by the analysis of biosynthesized
      nanoparticles using transmission electron microscopy techniques. This allowed
      determination of the partial amorphized structures of small bimetallic particles
      with cubic and multiple twined-like structures.

PMID- 16800557
TI  - Probing local environments in paramagnetic europium-substituted Keggin solids by
      31P magic angle spinning NMR spectroscopy.
AB  - Paramagnetic Eu-substituted Keggin oxopolytungstates crystallize in different
      forms, determined by the nature of the counterions. The crystal packing is in
      turn responsible for the variations in the geometry of paramagnetic Eu sites with
      respect to the anion core. We probed the paramagnetic environments in a series of
      Eu-substituted Keggin solids, by 31P magic angle spinning NMR spectroscopy. 31P
      spinning sideband envelopes are dominated by the electron-nuclear dipolar
      interaction. For the compounds under investigation, both the magnitude and the
      asymmetry parameter of the electron-nuclear dipolar coupling tensor are sensitive
      to the mutual arrangements of paramagnetic Eu sites in the crystal lattice. and
      also report on the stoichiometry of the anion. The electron-nuclear dipolar
      coupling tensors were calculated from the crystallographic coordinates and the
      experimentally determined effective magnetic moments, assuming a point dipole
      approximation. The computed tensors are in very good agreement with the
      experimental spectra. Furthermore, the P-Eu distance estimates, accurate to
      within 0.06-0.12 A, can be obtained directly from the magnitude of the electron
      nuclear dipolar coupling. This work demonstrates that 31P MAS NMR spectroscopy is
      a useful probe for investigating local environments in paramagnetic Keggin
      solids.

PMID- 16800558
TI  - Structure of sodium glycodeoxycholate micellar aggregates from small-angle X-ray
      scattering and light-scattering techniques.
AB  - Small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS)
      measurements were accomplished on sodium glycodeoxycholate (NaGDC) aqueous
      electrolyte solutions as a function of NaGDC and NaCl concentrations with the aim
      to determine with satisfactory approximation the NaGDC micellar aggregate
      structure at a gross molecular level, assuming monodispersity. Different
      conditions of interparticle interactions by varying ionic strength (NaCl
      concentration from 0 to 0.70 M) and NaGDC concentration (from 0.02 to 0.10 M)
      were studied. Smeared scattering intensities and electron pair distance
      distribution functions, radii of gyration, and aggregate heights are in
      satisfactory agreement with the corresponding functions calculated using a 2(1)
      helix as model. It is formed by trimers, each one composed by three NaGDC and
      nine H2O molecules related by a 3-fold rotation axis, and can be described by a
      hollow cylinder, probably filled by water molecules, characterized by a
      conventional radius of 23.7 A and a trimer repeat along the helical axis of 3.6
      A. The helix is considerably inhomogeneous since the volume of the cylinder
      occupied by NaGDC molecules is less than one-third of the total. On the other
      hand, calculations performed with the average radial electronic density of the
      helix without water molecules or totally filled by water molecules (a NaGDC/H2O
      molecular ratio of about 1/50) or by using a three-shell average radial
      electronic density, independently evaluated on absolute scale, do not show
      significant differences, thus supporting the helical model. The aggregate size
      increases for all the samples by increasing either the NaCl or NaGDC
      concentration. The NaGDC low concentration (0.02 M) samples with NaCl within the
      range 0.30-0.70 M are characterized by short cylindrical aggregates that do not
      give rise to sensible interference effects. This assertion is supported by the
      satisfactory fit between the observed apparent mean hydrodynamic radii and the
      calculated ones by means of the method of Ortega and Garcia de la Torre (J. Chem.
      Phys. 2003, 119, 9914), valid for rods with a length-to-diameter ratio > or = 0.1
      in dilute solution (noninteracting rods). The NaGDC moderate concentration (0.10
      M) samples with NaCl within the range 0.20-0.60 M are characterized by
      cylindrical aggregates that, in the presence of repulsive Coulombic interactions
      progressively more and more screened, produce interference effects, due to the
      hard-body repulsion and attractive forces, but the agreement between observed and
      calculated SAXS data is satisfactory. The results of the low and moderate NaGDC
      concentration samples seem to indicate that the aggregation number increase,
      produced by adding 0.10 M NaCl, is constant within an ionic strength range and
      occurs by the addition of oligomers formed by trimers. The samples with a
      variable NaGDC concentration (0.02-0.10 M) at a fixed and high NaCl concentration
      (0.6 M) contain cylindrical aggregates that give rise to an attractive term
      effect prevailing on the hard-body repulsive one. The same situation seems to
      occur in the NaGDC moderate concentration samples.

PMID- 16800559
TI  - Development of porosity in a char during reaction with steam or supercritical
      water.
AB  - Two series of activated carbon have been prepared by reaction of a char (from
      olive stones) with supercritical water (SCW) with the objective of studying the
      effect of temperature and residence time on the development of porosity. The
      results have been compared with those obtained using the same char but with
      classical activation with steam. Both procedures develop porosity, but (i) the
      reaction rate is critical in the development of porosity for steam but not for
      SCW activation, and (ii) SCW activation produces a larger development of
      microporosity at low degrees of burnoff, whereas steam produces more meso- and
      macroporosity. The differences have been explained by assuming that the mechanism
      for the carbon-water reaction is common but the transport properties of water in
      the supercritical state are more favorable to facilitate the access of water to
      the interior of the char particles. In contrast, when steam is used for the
      activation of the char, the diffusion of the molecules cannot keep up with the
      chemical rate and, consequently, the reaction is preferentially taking place at
      the most accessible surface sites, thus facilitating the development of larger
      pores and the widening of microporosity.

PMID- 16800560
TI  - Thermally induced polytype transformations among the layered double hydroxides
      (LDHs) of Mg and Zn with Al.
AB  - The hydrotalcite-like layered double hydroxide (LDH) of Mg with Al shows dramatic
      changes in the peaks arising from the (h0l)/(0kl) family of reflections in its
      powder X-ray diffraction pattern during thermal treatment. DIFFaX simulations
      show that these changes arise due to the transformation of the disordered 3R1
      polytype into the 1H polytype on dehydration. The 1H polytype is an essential
      precursor to the decomposition reaction, which results in the formation of an
      oxide residue with the rock salt structure. In contrast, the LDH of Zn with Al
      does not undergo any such transformation, retaining the structure of the 3R1
      polytype until decomposition into the oxide residue. Given the poor octahedral
      site preference of the Zn2+ ion, the 1H polytype is neither structurally stable
      nor is it topochemically necessary for the thermal decomposition of the Zn-Al
      LDH, the end product of the decomposition reaction being an oxide with the
      wurtzite structure.

PMID- 16800561
TI  - Thermal properties and mixing state of ethylene glycol-water binary solutions by
      calorimetry, large-angle X-ray scattering, and small-angle neutron scattering.
AB  - Thermal properties and mixing states of ethylene glycol (EG)-water binary
      solutions in the entire mole fraction range of EG, 0 < or = x(EG) < or = 1, have
      been clarified by using differential scanning calorimetry (DSC), large-angle X
      ray scattering (LAXS), and small-angle neutron scattering (SANS) techniques. The
      DSC curves obtained have shown that the EG-water solutions over the range of EG
      mole fraction 0.3 < or = x(EG) < or = 0.5 are kept in the supercooling state
      until approximately 100 K, and those in the range of 0.6 < or = x(EG) < or = 0.8
      are vitrified, and those in the ranges of 0 < x(EG) < or = 0.2 and 0.9 < or =
      x(EG) < 1 are crystallized. The radial distribution function (RDF) for pure EG
      obtained from the LAXS measurements has suggested that a gauche conformation of
      an EG molecule is favorable in the liquid. The RDFs for the EG-water solutions
      have shown that the structure of the binary solutions moderately changes from the
      inherent structure of EG to the tetrahedral-like structure of water when the
      water content increases. The SANS intensities for deuterated ethylene glycol
      (HOCD2CD2OH) (EGd4)-water solutions at x(EG) = 0.4 and 0.6 have not been
      significantly observed in the temperature range from 298 to 173 K, showing that
      EG and water molecules are homogeneously mixed. On the other hand, the SANS
      intensities at x(EG) = 0.2 and 0.9 have been strengthened when the temperature
      decreases due to crystallization of the solutions. On the basis of all the
      present results, a relation between thermal properties of EG-water binary
      solutions and their mixing states clarified by the LAXS and SANS measurements has
      been discussed at the molecular level.

PMID- 16800562
TI  - Curing kinetics of o-cresol formaldehyde epoxy resin and succinic anhydride
      system catalyzed by tertiary amine.
AB  - The kinetics of the cure reaction for system of o-cresol formaldehyde epoxy resin
      (o-CFER)/succinic anhydride (SA) and tertiary amine as a catalyst was
      investigated with a differential scanning calorimeter (DSC). Autocatalytic
      behavior was shown in the first stages of the cure for the system, which was well
      described by the model proposed by Kamal that includes two rate constants, k1 and
      k2, and two reaction orders, m and n. The overall reaction order, m + n, is in
      the range 2.1-2.6, and the activation energy for k1 and k2 was 109 and 72.0
      kJ/mol, respectively. In the later stages, a cross-linked network was formed and
      the cure reaction is mainly controlled by diffusion. Diffusion factor, f(alpha),
      was introduced into Kamal's equation, then the calculated values agree very well
      with the experimental data. The molecular mechanism of this curing reaction was
      discussed.

PMID- 16800563
TI  - Electronic properties of capped, finite-length armchair carbon nanotubes in an
      electric field.
AB  - This study investigates the electronic properties of finite-length armchair
      carbon nanotubes in an electric field (E) using a single-pi-band tight-binding
      model. Three different tip configurations are considered, namely, open ends with
      hydrogen terminations (H-terminations), one end capped with half of C60 fullerene
      and the other end open with H-terminations, and both ends capped with half of C60
      fullerene. In general, the electronic states and energy gaps of low-energy
      electronic structures are highly sensitive to changes in the direction and
      magnitude of the applied electric field and to the tip configuration. The present
      results show that the electric field induces a strong modulation of the state
      energies and energy gaps of the current nanotubes, changes their energy spacings,
      and prompts the occurrence of semiconductor-metal transitions (SMTs). It is found
      that the SMTs occur more frequently as the direction of the electric field
      approaches the symmetry axis or when its magnitude becomes sufficiently large.
      The present results also indicate that the Fermi levels and energy gaps of the
      three nanotubes considered in this study are strongly influenced by the cap
      configuration. Finally, the convergent decay behavior of the energy gap which is
      observed as the length of the nanotube is increased is also strongly dependent on
      the tip configuration.

PMID- 16800564
TI  - Infrared spectroscopy of single-walled carbon nanotubes.
AB  - By using the spectral moments method, we calculate the infrared spectra of chiral
      and achiral single-walled carbon nanotubes (SWCNTs) of different diameters and
      lengths. We show that the number of the infrared modes, their frequencies, and
      intensities depend on the length and chirality of the nanotubes. Furthermore, the
      dependence of the infrared spectrum as a function of the size of the SWCNT bundle
      is analyzed. These predictions are useful to interpret the experimental infrared
      spectra of SWCNTs.

PMID- 16800565
TI  - Conductive-matrix-mediated alkaline Fe(III/VI) charge transfer: three-electron
      storage, reversible super-iron thin film cathodes.
AB  - An extended conductive matrix facilitates a 100-fold enhancement in charge
      storage for reversible Fe(III/VI) super-iron thin films. These films were
      deposited, by electrochemical reduction of Na2FeO4, with an intrinsic high
      capacity 3 e- cathodic storage of 485 mAh g(-1). Whereas 3 nm Fe(III/VI) films
      exhibited a high degree of reversibility (throughout 100 charge/discharge
      cycles), thicker films had been increasingly passive toward the Fe(VI) charge
      transfer. Films were alternatively deposited on either smooth or on extended
      conductive matrixes composed of high-surface-area Pt, Ti, and Au and probed
      galvanostatically and via cyclic voltammetry. A 100 nm Fe(VI) cathode, on the
      extended conductive matrixes, sustained 100-200 reversible three-electrode
      charge/discharge cycles, and a 19 nm thin film cathode sustained 500 such cycles.
      With a metal hydride anode, full cell storage was probed, and a 250 nm super-iron
      film cathode film sustained 40 charge/discharge cycles, and a 25 nm film was
      reversible throughout 300 cycles. Fe(VI) salts exhibit higher cathodic capacity
      and environmental advantages, and the films are of relevance toward the next
      generation charge storage chemistry for reversible cathodes.

PMID- 16800566
TI  - Porosity effects on electron transport in TiO2 films and its application to dye
      sensitized solar cells.
AB  - Porosity (P) of TiO2 film in dye-sensitized solar cells affects the light
      absorption coefficient and electron diffusion coefficient. A theoretical
      analytical expression of the intensity-modulated photocurrent spectroscopy (IMPS)
      response involving the light absorption coefficient and the electron diffusion
      coefficient as a function of the porosity has been proposed to investigate the
      influence of TiO2 film porosity on the characteristics of electron transport. The
      incident photon-to-current conversion efficiency (IPCE) and electron transit time
      depending on the porosity have been analyzed illuminating from both the
      electrolyte side (IE) and the substrate side (IS). The IPCE derived from the IMPS
      response reaches its maximum at a porosity of around 30% for IE and 41% for IS,
      respectively. Electron transit time increases with increasing the porosity for
      IE, while it declines when P < 0.41 for IS, which is attributable to the
      influence of the RC time constant. It has also been found that a larger RC time
      constant will lead to a longer transit time. The electron diffusion coefficient
      calculated from the transit time for IE corresponds to the results from the
      porosity reported in previous literature, which indicates that the dependence of
      the electron transit time tau(d) on the porosity is justifiable. The diffusion
      coefficient calculated for a larger RC time constant approaches the value from
      the literature when P > or = 0.41, while it is not practicable when P < 0.41 for
      IS.

PMID- 16800567
TI  - Pressure effects on lipidic direct phases: the dodecyl trimethyl ammonium
      chloride-water system.
AB  - The direct lyotropic polymorphism of dodecyltrimethylammonium chloride (DTAC) was
      investigated by synchrotron X-ray diffraction at different water concentrations
      under compression up to 2 kbar, i.e., in the pressure intermediate range where
      interesting biophysical transformations occur and the functional characteristics
      of cell membranes are altered. The results show that pressure induces the
      transition from the hexagonal phase to the micellar Pm3n cubic phase in hydrated
      samples (c between 0.5 and 0.6, c being the weight concentration of lipid in the
      mixture) and the transition from the bicontinuous Ia3d cubic phase to the
      hexagonal phase in drier samples (c = 0.8). By increasing the pressure on very
      dry samples, a lamellar L(alpha) phase was observed to form transitorily at the
      Ia3d cubic-hexagonal phase transition. Phase compressibility and then the lipid
      and water partial molecular compressibilities were derived as a function of
      pressure and concentration. As a result, we assessed the very low compressibility
      of the hydration water within the lipid phases, and we demonstrated that the
      compressibility of DTAC is very dependent on pressure. Moreover, the molecular
      parameters of DTAC calculated in the different phases during compression
      confirmed that pressure induces small but continuous conformational changes,
      definitely different from the large changes observed in lipid molecules forming
      type II structures.

PMID- 16800568
TI  - Voltammetric monitoring of gold nanoparticle formation facilitated by glycyl-L
      tyrosine: relation to electronic spectra and transmission electron microscopy
      images.
AB  - Voltammetric techniques have been introduced to monitor the formation of gold
      nanoparticles produced via the reaction of the amino acid glycyl-L-tyrosine with
      Au(III) (bromoaurate) in 0.05 M KOH conditions. The alkaline conditions
      facilitate amino acid binding to Au(III), inhibit the rate of reduction to Au(0),
      and provide an excellent supporting electrolyte for voltammetric studies. Data
      obtained revealed that a range of time-dependent gold solution species are
      involved in gold nanoparticle formation and that the order in which reagents are
      mixed is critical to the outcome. Concomitantly with voltammetric measurements,
      the properties of gold nanoparticles formed are probed by examination of
      electronic spectra in order to understand how the solution environment present
      during nanoparticle growth affects the final distribution of the nanoparticles.
      Images obtained by the ex situ transmission electron microscopy (TEM) technique
      enable the physical properties of the nanoparticles isolated in the solid state
      to be assessed. Use of this combination of in situ and ex situ techniques
      provides a versatile framework for elucidating the details of nanoparticle
      formation.

PMID- 16800569
TI  - Oxygen sites and network coordination in sodium germanate glasses and crystals:
      high-resolution oxygen-17 and sodium-23 NMR.
AB  - Sodium germanate glasses are well-studied materials in which, unlike silicates
      but analogous to borates, the major structural consequence of alkali addition is
      generally thought to involve a coordination number increase of the network
      forming Ge cations. However, the nature of this change, in particular quantifying
      fractions of nonbridging oxygens and of five- and/or six-coordinated Ge, has
      remained unresolved. We present here high-resolution 17O results, including
      triple-quantum MAS NMR (3QMAS), on a series of crystalline model compounds that
      allow the definition of ranges of chemical shifts corresponding to oxygens bonded
      to various coordinations of Ge. These include quartz- and rutile-structured GeO2,
      Na4Ge9O20, Na2Ge4O9, and Na2GeO3 (germanium dioxide, sodium enneagermanate,
      sodium tetragermanate, and sodium metagermanate). 3QMAS spectra of Na-germanate
      glasses ranging from 0% to 27% Na2O clearly show the development of partially
      resolved peaks as alkali is added, corresponding to signals from nonbridging
      oxygens (in the highest Na glasses) and to oxygen bridging between one four
      coordinated and one higher coordinated Ge. As in conventional models of this
      system, nonbridging oxygen contents are much lower than in corresponding
      silicates. Although we do not directly distinguish between five- and six
      coordinated Ge, modeling of bridging oxygen populations and comparison with
      measured speciation suggest that substantial proportions of both species are
      likely to be present. High-field 23Na MAS NMR shows systematic decreases in mean
      Na-O bond distance and/or coordination number with increasing alkali content that
      can be compared with published results for high-temperature liquids. These
      results, as well as comparison of molar volumes of glasses and high-temperature
      liquids, suggest the possibility of significant temperature effects on liquid
      structure.

PMID- 16800570
TI  - Influence of the structural properties of poly(vinylidene fluoride) membranes on
      the heterogeneous nucleation rate of protein crystals.
AB  - In this study, the influence of the morphological parameters of microporous
      poly(vinylidene fluoride) (PVDF) membranes on the heterogeneous nucleation rate
      of hen egg white lysozyme (HEWL) crystals has been investigated. Experiments have
      been carried out on membranes prepared by non-solvent-induced phase inversion
      method, using PVDF-co-hexafluoropropylene (Kynarflex 2800) and PVDF homopolymer
      (Kinar 460), and adding LiCl and poly(vinylpyrrolidone) (PVP) in order to
      modulate the pore structure. From a theoretical point of view, the free Gibbs
      energy balance for the formation of a critical nucleus has been adapted to
      nonporous surfaces, thus obtaining a mathematical correlation between the energy
      nucleation barrier, the membrane porosity, and the contact angle between protein
      solution and polymeric substrate. The energetic barrier to heterogeneous
      nucleation was found to increase at higher contact angles-according to the
      prediction of classical theory-and to decrease at higher porosity. For instance,
      the predicted deltaG(het)/deltaG(hom) ratio for PVDF-Kynarflex (PVP 2.5%)
      membrane with porosity of 0.11 was 0.30, 35% lower with respect to the value
      calculated by the Volmer equation for a dense polymeric matrix having the same
      contact angle (87.4 +/- 5.8 degrees). In addition, the effect of the membrane
      pore size, porosity, and thickness on the removal rate of solvent have been
      discussed. For example, the transmembrane flux through PVDF-Kynar (LiCl 5.0%)
      membrane was 12% inferior than the one measured under the same experimental
      conditions through PVDF-Kynarflex (LiCl 7.5%) membrane, the latter having similar
      pore size and thickness but higher porosity (0.44 vs 0.32). The possibility to
      achieve rapidly a high level of supersaturation is expected to increase the
      nucleation rate. In general, measurements performed during crystallization tests
      carried out at pH 4.5 in NaAc 0.05 M buffer with different precipitant (NaCl)
      concentrations agree with the predicted trends.

PMID- 16800571
TI  - Singlet energy migration along an alternating block copolymer of oligothiophene
      and oligosilylene in solution.
AB  - The singlet excited-state properties of the block copolymers of oligothiophene
      and oligosilylene in solution were investigated with several fast spectroscopic
      methods. Time-resolved fluorescence measurements at room temperature and in a
      glassy matrix revealed that the singlet excited states of the block copolymers
      are deactivated accompanying structural changes of the polymer. It became clear
      from the transient absorption spectroscopy that the absorption peak of the
      singlet excited state shifted to the longer wavelength side compared to that of
      the corresponding oligothiophenes because of the sigma-pi conjugation of the
      oligothiophene and oligosilylene. The intersystem crossing process generating the
      triplet excited state was also revealed by the transient absorption spectroscopy.
      Energy migration along the polymer chain was revealed by the fluorescence
      anisotropy measurements. The time constant for the energy migration became faster
      as the size of the oligothiophene in the polymer repeating unit became shorter.
      From comparison with the Forster theory, the energy migration process was
      attributed to an incoherent hopping mechanism.

PMID- 16800572
TI  - Reversible micelle-vesicle conversion of oleyldimethylamine oxide by pH changes.
AB  - A preliminary study on the reversible micelle-vesicle conversion of
      oleyldimethylamine oxide [Kawasaki, H. et al. J. Phys. Chem. B. 2002, 106, 1524 ]
      is extended in the present study. In the presence of 0.01 M NaCl at a surfactant
      concentration of 0.05 M, a micelle-to-vesicle conversion with increasing degree
      of ionization alpha takes place in the following sequence: growth of fibrous
      micelle (alpha < 0.2), a fused network (alpha approximately 0.3), fibrous
      micelles + (perforated) vesicles (alpha = 0.4), and vesicles + lamellae (alpha =
      0.5). Viscoelasticity correspondingly varies from the Maxwell-type behavior of
      the entangled network of fibrous micelles to the gel-like behavior of vesicle
      suspensions, via a fluid solution-like behavior of the fused network. This phase
      sequence is in contrast with the case of no added salt where no branching of
      micelles is observed, and long micelles and bilayers (vesicles + lamellae)
      coexist at alpha = 0.5. In water, a state of the lowest viscoelasticity occurs
      around alpha = 0.2 for both surfactant concentrations 0.05 and 0.15 M. Synergism
      between protonated and nonprotonated amine oxide headgroups is observed despite
      low ionic strengths. From the time course of the reversible micelle-vesicle
      conversion, vesicles seem to be formed from threadlike micelles within 25 h
      according to the shear moduli, while a longer conversion time is suggested by a
      flow property (viscosity). Shear thickening behavior is observed at alpha = 0.2
      and 0.4 in 0.01 M NaCl but not in water.

PMID- 16800573
TI  - Pt3Ru6 clusters supported on gamma-Al2O3: synthesis from Pt3Ru6(CO)21(mu3-H)(mu
      H)3, structural characterization, and catalysis of ethylene hydrogenation and n
      butane hydrogenolysis.
AB  - The supported clusters Pt-Ru/gamma-Al2O3 were prepared by adsorption of the
      bimetallic precursor Pt3Ru6(CO)21(mu3-H)(mu-H)3 from CH2Cl2 solution onto gamma
      Al2O3 followed by decarbonylation in He at 300 degrees C. The resultant supported
      clusters were characterized by infrared (IR) and extended X-ray absorption fine
      structure (EXAFS) spectroscopies and as catalysts for ethylene hydrogenation and
      n-butane hydrogenolysis. After adsorption, the nu(CO) peaks characterizing the
      precursor shifted to lower wavenumbers, and some of the hydroxyl bands of the
      support disappeared or changed, indicating that the CO ligands of the precursor
      interacted with support hydroxyl groups. The EXAFS results show that the metal
      core of the precursor remained essentially unchanged upon adsorption, but there
      were distortions of the metal core indicated by changes in the metal-metal
      distances. After decarbonylation of the supported clusters, the EXAFS data
      indicated that Pt and Ru atoms interacted with support oxygen atoms and that
      about half of the Pt-Ru bonds were maintained, with the composition of the metal
      frame remaining almost unchanged. The decarbonylated supported bimetallic
      clusters reported here are the first having essentially the same metal core
      composition as that of a precursor metal carbonyl, and they appear to be the best
      defined supported bimetallic clusters. The material was found to be an active
      catalyst for ethylene hydrogenation and n-butane hydrogenolysis under conditions
      mild enough to prevent substantial cluster disruption.

PMID- 16800574
TI  - Role of the Fermi surface in adsorbate-metal interactions: an energy
      decomposition analysis.
AB  - We present the result of a fragment-based energy decomposition analysis on some
      molecule-surface interactions. The analysis allows us to quantify the Pauli
      repulsion, its relief, and the attractive orbital interaction energy. In a metal,
      the existence of incompletely occupied energy bands causes significant relief of
      the Pauli repulsion due to escape of antibonding electrons to unoccupied states
      at the Fermi energy. This is the key electronic structure feature of metals that
      causes metal-molecule bond energies to be stronger and dissociation barriers of
      chemisorbed molecules to be much lower than those in comparable systems with no
      or one metal atom. As examples, we discuss the energy decomposition for the
      activated dissociation of hydrogen on the Cu surface and its unactivated
      dissociation on Pd, and for the (activated) chemisorption of N2 on W. We show
      that in all cases the relief of Pauli repulsion is of crucial importance for the
      chemisorption energy and for the low (or nonexistent) dissociation barriers. The
      barrier to the chemisorption well for nitrogen on tungsten is clearly related to
      a late relief of the Pauli repulsion. The relief of Pauli repulsion is important
      in lowering the barrier to dissociation of H2 on both Cu and Pd, but the
      difference in barrier heights for Cu and Pd appears to not be due to stronger
      relief of Pauli repulsion on Pd but primarily to the Pauli repulsion itself being
      stronger on Cu than on Pd, the relief energy being quite comparable on the two
      metals.

PMID- 16800575
TI  - Structural effects of electrochemical oxidation of formic acid on single crystal
      electrodes of palladium.
AB  - Structural effects on the rates of formic acid oxidation have been studied on
      Pd(111), Pd(100), Pd(110), and Pd(S)-[n(100) x (111)] (n = 2-9) electrodes in 0.1
      M HClO4 containing 0.1 M formic acid with use of voltammetry. On the low index
      planes of Pd, the maximum current density of formic acid oxidation (jP) increases
      in the positive scan as follows: Pd(110) < Pd(111) < Pd(100). This order differs
      from that on the low index planes of Pt: Pt(111) < Pt(100) < Pt(110). Pd(S)
      [n(100) x (111)] electrodes with terrace atomic rows n > or = 3 have almost the
      same jP as Pd(100), except Pd(911) n = 5. The value of jP on Pd(911) n = 5 is 20%
      higher than those of the other surfaces. Pd(311) n = 2, of which the first layer
      is composed of only step atoms, has the lowest jP in the Pd(S)-[n(100) x (111)]
      series. The adsorption geometry of the reaction intermediate (formate ion) is
      optimized by using density functional theory.

PMID- 16800576
TI  - Effect of an adsorbent on recombination and band-edge movement in dye-sensitized
      TiO2 solar cells: evidence for surface passivation.
AB  - The mechanism by which the adsorbent guanidinium affects the open-circuit
      photovoltage of dye-sensitized TiO2 nanocrystalline solar cells was investigated.
      The influence of the guanidinium cation on the rate of recombination and band
      edge movement was measured by transient photovoltage. When guanidinium is present
      in the electrolyte recombination becomes slower by a factor of about 20. At the
      same time, the adsorbent causes the band edges to move downward, toward positive
      electrochemical potentials, by 100 mV. The collective effect of both a downward
      shift of the band edges and slower recombination, owing to the presence of
      guanidinium, results in an overall improvement in the open-circuit photovoltage.

PMID- 16800577
TI  - Incorporation of Co(II) in dealuminated BEA zeolite at lattice tetrahedral sites
      evidenced by XRD, FTIR, diffuse reflectance UV-Vis, EPR, and TPR.
AB  - A CoSiBEA zeolite is prepared by a two-step postsynthesis method that consists of
      first creating vacant T-sites with associated silanol groups by dealumination of
      TEABEA zeolite with nitric acid and then impregnating the resulting SiBEA zeolite
      with an aqueous solution of Co(NO3)2. The incorporation of Co into lattice sites
      of SiBEA is evidenced by XRD. The consumption of OH groups is monitored by FTIR.
      The presence of Co in its II oxidation state and in tetrahedral coordination is
      evidenced by diffuse reflectance UV-vis and EPR spectroscopy. The very high
      reduction temperature (1120 K) of cobalt in CoSiBEA zeolite determined by TPR
      confirms that Co interacts strongly with the zeolite support, consistent with
      lattice tetrahedral (T(d)) coordination.

PMID- 16800578
TI  - FTIR spectroscopy of alcohol and formate interactions with mesoporous TiO2
      surfaces.
AB  - The effects of pH and ultraviolet (UV) light with ligated formic acid on
      mesoporous TiO2 were characterized by transmission Fourier transform infrared
      (FTIR) spectroscopy and compared with adsorbed formate complexes. Surface
      modified anatase thin films were prepared from acidic aqueous nanoparticulate
      anatase suspensions diluted with methanol and ethanol. Bands assigned to
      carboxylic acid groups displayed unique bonding character in the ligated formic
      acid on the anatase surface. For increased proton concentrations in the films,
      separation in -COO stretching bands (delta nu) for formic acid increased
      (increase in frequency for nuC=O and decrease in frequency for nuC-O). With UV
      exposure, surface-bound organics were rapidly removed by photocatalytic oxidation
      at 40 degrees C and 40% relative humidity (RH). In addition, the delta nu of the
      formic acid bands decreased as organics were mineralized to carbonates and CO2
      with UV light. Aqueous formic acid adsorption experiments showed a distinctly
      different bonding environment lacking carbonate, and the delta nu for the
      carboxylic groups indicated a bridging bidentate coordination. The delta nu of
      the bands increased with increasing proton concentration, with both bands
      shifting to higher wavenumbers. The shifts may be ascribed to the influence of
      protonation on surface charge and the effect of that charge on the
      electronegativity of carboxylate groups bound to the surface. As alcohols are
      used in the mesoporous TiO2 solar cell preparation, implications of these surface
      modifications to dye-sensitized photovoltaics are discussed.

PMID- 16800579
TI  - Hyperthermal reactions of O and O2 with a hydrocarbon surface: direct C-C bond
      breakage by O and H-atom abstraction by O2.
AB  - A C-C bond-breaking reaction has been observed when a beam containing
      hyperthermal oxygen was directed at a continuously refreshed saturated
      hydrocarbon liquid (squalane) surface. The dynamics of this C-C bond-breaking
      reaction have been investigated by monitoring time-of-flight and angular
      distributions of the volatile product, OCH3 or H2CO. The primary product is
      believed to be the methoxy radical, OCH3, but if this radical is highly
      internally excited, then it may undergo secondary dissociation to form
      formaldehyde, H2CO. Either the primary or the secondary product may scatter
      directly into the gas phase before thermal equilibrium with the surface is
      reached, or they may become trapped on the surface and desorb in thermal
      equilibrium with the surface. Direct, single-collision scattering events that
      produce a C-C bond-breaking product are described with a kinematic picture that
      allows the determination of the effective surface mass encountered by an incident
      O atom, the atom-surface collision energy in the center-of-mass frame, and the
      fraction of the center-of-mass collision energy that goes into translation of the
      scattered gaseous product and the recoiling surface fragment. The dynamical
      behavior of the C-C bond-breaking reaction is compared with that of the H-atom
      abstraction reaction, which was the subject of an earlier study. Another
      reaction, H-atom abstraction by O2 (which is present in the hyperthermal beam),
      has also been observed, and the dynamics of this reaction are compared with the
      inelastic scattering dynamics of O2 and the dynamics of H-atom abstraction by O.
      The dynamics involving direct inelastic and reactive scattering of O2 are also
      described in terms of a kinematic picture where the incident O2 molecule is
      viewed as interacting with a local region of the surface.

PMID- 16800580
TI  - Products and reaction sequences in tetrahydrofuran exposed to low-energy
      electrons.
AB  - Electron-stimulated reactions in solid films of tetrahydrofuran (THF), condensed
      on Kr spacers deposited on a Pt substrate, or directly onto the substrate, were
      induced and monitored simultaneously with use of high-resolution electron-energy
      loss spectroscopy in the ranges of vibrational and electronic excitations. The
      spectra of the molecular films obtained after a certain time of exposure to
      electrons at incident energies of 14 and 15.5 eV were analyzed and different
      products were identified. Besides an aldehyde, which is the main product,
      olefins, conjugated olefins, as well as CO were identified. Closer investigation
      of the reactions of propionaldehyde, as a model aldehyde, demonstrates that CO
      appears in THF as a secondary product (i.e., from the intermediate aldehyde). On
      the basis of the cross sections for the formation of an aldehyde from THF, of CO
      from propionaldehyde, and for the loss of propionaldehyde under electron impact,
      the reaction sequences were evaluated with the help of a kinetic model. This
      analysis suggests that some CO could also be formed directly from THF (i.e.,
      without involvement of an intermediate aldehyde).

PMID- 16800581
TI  - Modification of monomolecular self-assembled films by nitrogen-oxygen plasma.
AB  - The modification of octadecanethiolate self-assembled monolayers on Au and Ag by
      nitrogen-oxygen downstream microwave plasma with variable oxygen content (up to
      1%) has been studied by synchrotron-based high-resolution X-ray photoelectron
      spectroscopy. The primary processes were dehydrogenation, desorption of
      hydrocarbon and sulfur-containing species, and the oxidation of the alkyl matrix
      and headgroup-substrate interface. The exact character and the rates of the
      plasma-induced changes were found to be dependent on the substrate and plasma
      composition, with the processes in the aliphatic matrix and headgroup-substrate
      interface being mostly decoupled. In particular, the rates of all major plasma
      induced processes were found to be directly proportional to the oxygen content in
      the plasma, which can be, thus, considered as a measure of the plasma reactivity.
      Along with the character of the observed changes, exhibiting a clear dominance of
      the oxidative processes, this suggests that the major effect of the oxygen
      nitrogen downstream microwave plasma is provided by reactive oxygen-derived
      species in the downstream region, viz. long-living oxygen radicals and metastable
      species.

PMID- 16800582
TI  - Molecular dynamics study of 2-nitrophenyl octyl ether and nitrobenzene.
AB  - The pure organic liquids nitrobenzene (NB) and 2-nitrophenyl octyl ether (NPOE)
      have been studied by means of molecular dynamics simulations. Both solvents are
      extremely important in various interfacial processes, mainly connected with ion
      transfer taking place across the interface with water. Thermodynamic (mass
      density, enthalpy of vaporization, isothermal compressibility, dipole moment) and
      dynamic (viscosities and self-diffusion coefficients) properties of both liquids
      have been calculated and are in very good agreement with the experimental data.
      In the case of NB, several potentials have been tested and the obtained results
      compared and discussed. In most cases, the OPLS all-atom potential gives results
      that are in better agreement with available experimental values. Atomic radial
      distribution functions, dihedral and angle distributions, as well as dipole
      orientation correlation functions are used to probe the structure and
      interactions of the bulk molecules of both organic solvents. These were seen to
      be very similar in terms of structure and thermodynamics, but quite distinct in
      terms of dynamic behavior, with NPOE showing a much slower dynamic response than
      NB. A simulation study of the simple Cl- and K+ ions dissolved in both solvents
      has been also undertaken, revealing details about the diffusion and solvation
      mechanisms of these ions. It was found that in both liquids the positive
      potassium ion is solvated by the negative end of the molecular dipole, whereas
      the negative chloride ion is solvated by the positive end of the dipole.

PMID- 16800583
TI  - Bimolecular networks and supramolecular traps on Au(111).
AB  - We demonstrate the formation of intermixed phases and self assembled molecular
      templates on the Au(111) surface. The templates are stabilized by hydrogen
      bonding between melamine molecules with trigonal symmetry and linear PTCDI
      (perylene tetra-carboxylic di-imide) molecules. When annealed, these molecules
      spontaneously form either a chiral intermixed phase or a honeycomb arrangement in
      which vertexes and edges correspond respectively to melamine and PTCDI molecules.
      We also observe minority phases with more complex intermolecular junctions. The
      use of these networks as templates is demonstrated by the controlled capture of
      fullerenes within the pores of the network to form dimers, hexamers, and
      heptamers. Our results confirm that bimolecular templates can be realized on a
      range of substrates.

PMID- 16800584
TI  - Dynamics of the interaction of vapor-deposited copper with alkanethiolate
      monolayers: bond insertion, complexation, and penetration pathways.
AB  - We have investigated the interaction of vapor-deposited copper with -CH3, -OH, 
      OCH3, -COOH, and -CO2CH3 terminated alkanethiolate self-assembled monolayers
      (SAMs) adsorbed on polycrystalline Au using time-of-flight secondary ion mass
      spectrometry and density functional theory calculations. For -OH, -COOH, and 
      CO2CH3 terminated SAMs measurements indicate that for all copper coverages there
      is a competition between Cu atom bond insertion into C-O bonds, stabilization at
      the SAM/vacuum interface, and penetration to the Au/S interface. In contrast, on
      a -OCH3 terminated SAM Cu only weakly interacts with the methoxy group and
      penetrates to the Au substrate, while for a -CH3 terminated SAM deposited copper
      only penetrates to the Au/S interface. The insertion of copper into C-O terminal
      group bonds is an activated process. We estimate that the barriers for Cu
      insertion are 55 +/- 5 kJ mol(-1) for the ester, 50 +/- 5 kJ mol(-1) for the
      acid, and 55 +/- 5 kJ mol(-1) for the hydroxyl terminated SAMs. The activation
      barrier for the copper insertion is much higher for the -OCH3 SAM. Copper atoms
      with energies lower than the activation barrier partition between complexation
      (weak interaction) with the terminal groups and penetration through the monolayer
      to the Au/S interface. Weakly stabilized copper atoms at the SAM/vacuum interface
      slowly penetrate through the monolayer. In contrast to the case of Al deposition,
      C-O bond insertion is favored over C=O, C-H, and C-C bond insertion.

PMID- 16800585
TI  - The surface chemistry of propylene, 1-iodopropane, and 1,3-diiodopropane on MoAl
      alloy thin films formed on dehydroxylated alumina.
AB  - The adsorption of C3 hydrocarbons propylene, 1-iodopropane, and 1,3-diiodopropane
      is studied in ultrahigh vacuum on a molybdenum-aluminum alloy formed by
      molybdenum hexacarbonyl reaction with a planar alumina film grown on a Mo(100)
      substrate. Carbon-iodine bond scission occurs below approximately 200 K to
      deposit iodine, and form propyl species from 1-iodopropane and a C3 metallacycle
      from 1,3-diiodopropane. Propyl species either undergo beta-hydride elimination to
      yield propylene or hydrogenate to form propane. Propylene adsorbs as both pi- and
      di-sigma-bonded species, and the di-sigma form hydrogenates to yield propane,
      where the addition of the first hydrogen to form propyl species is slower than
      the second hydrogenation step to yield propane. Propylene also thermally
      decomposes on the surface to desorb hydrogen and deposit carbon where the
      methylyne group is the most, and the methyl group the least reactive. The
      metallacyclic intermediate reacts to give an allylic intermediate, which forms
      propylene, but also decomposes by C-C bond cleavage to evolve ethylene and
      deposit methylene species on the surface. This is a key step in the mechanism
      proposed for heterogeneously catalyzed olefin metathesis and this is the first
      time that this chemistry has been directly identified in ultrahigh vacuum.

PMID- 16800586
TI  - Influence of the preparation method on the surface characteristics and activity
      of boron-nitride-supported noble metal catalysts.
AB  - In this article, we report how variations in the preparation method of boron
      nitride-supported noble metal catalysts may influence the surface characteristics
      of the active phase and consequently the potential applications as catalysts for
      oxidation reactions. The deposition and the dispersion of the active phase are
      strongly influenced by the preparation process and in particular by the protic or
      aprotic solvent used as the dispersing phase; in this study, benzene, glyme,
      water, tetrahydrofuran, diglyme, 2-propanol, and glycol have been investigated.
      Characterization techniques, such as Brunauer-Emmett-Teller, X-ray diffraction,
      transmission electron microscopy, Fourier transform infrared spectroscopy, and
      thermogravimetric analysis, have been used to study the influence of the choice
      of a solvent phase on the particle size and dispersion of the metal deposited on
      the BN support. The modifications undergone by the support during the deposition
      of palladium in different solvents have also been studied. Through the use of the
      same deposition procedure, different noble metal coatings (Pt, Pd, Au, and Ag)
      have been prepared. The acidic and redox characteristics of the resulting samples
      were characterized by temperature-programmed reduction and adsorption
      microcalorimetry. The catalytic performances of these materials were tested in
      the total oxidation of methane in lean conditions (excess oxygen and presence of
      water).

PMID- 16800587
TI  - Direct measurement of ion accumulation at the electrode electrolyte interface
      under an oscillatory electric field.
AB  - The ionic charge accumulation at the metal-electrolyte interface is directly
      measured by using differential interferometry as a function of magnitude and
      frequency (2-50 kHz) of external electric field. The technique developed probes
      the ion dynamics confined to the electrical double layer. The amplitude of
      modulation of the ions is linearly proportional to the amplitude of applied
      potential. The linearity is observed up to high electrode potentials and salt
      concentrations. The frequency response of the ion dynamics at the interface is
      interpreted in terms of the classical RC model.

PMID- 16800588
TI  - Heterogeneous reactions of sulfur dioxide on typical mineral particles.
AB  - The heterogeneous reaction of SO2 on Al2O3, CaO, TiO2, MgO, FeOOH, Fe2O3, MnO2,
      and SiO2, as well as authentic aerosol sample, was investigated by using a White
      Cell coupled with in situ-FTIR and Diffuse Reflectance Infrared Fourier Transform
      Spectroscopy (DRIFTS). Simultaneous observations of reactants and products were
      performed to obtain full information on the mechanism and kinetics of the
      reactions. SO2 was irreversibly adsorbed to form surface sulfite (SO3(2-)),
      bisulfite (HSO3(-)), and sulfate (SO4(2-)). The reactivity order of these
      particles is the following: FeOOH >Al2O3 > mixture > MgO > Fe2O3 > SiO2. Field
      collected aerosol showed significant activity for the oxidation of SO2. The
      uptake coefficient of SO2 on Al2O3 with different acidity varied in the order of
      basic Al2O3 > neutral Al2O3 > acidic Al2O3. The surface-active oxygen and
      hydroxyl might be the key factors for the conversion of SO2 to SO4(2-). The
      faster reaction rate could be achieved with greater surface area on particles
      with the same mass. On the basis of the same surface area Fe2O3 could be most
      reactive in the reaction with SO2 compared with all other particles. The apparent
      rate constants were determined to be 1.35 x 10(-2) and 9.4 x 10(-3) for uptake on
      Al2O3 and MgO, respectively, which are the same as the results of other
      scientists.

PMID- 16800589
TI  - CF4 on carbon nanotubes: physisorption on grooves and external surfaces.
AB  - We present the combined results of a computer simulation and adsorption isotherm
      investigation of CF4 films on purified HiPco nanotubes. The experimental
      measurements found two substeps in the adsorption data. The specific surface area
      of the sample and the coverage dependence of the isosteric heat of adsorption of
      the films were determined from the measurements. The simulations, conducted for
      homogeneous bundles of close-ended tubes, also found two substeps in the first
      layer data: one corresponding to adsorption on the grooves and a second one, at
      higher pressures, corresponding to adsorption on the outside surface of the
      tubes. Our computer simulations are in very good agreement with the experimental
      data.

PMID- 16800590
TI  - Controlled nucleation and growth of CdS nanoparticles in a polymer matrix.
AB  - In-situ synchrotron X-ray diffraction (XRD) was used to monitor the thermal
      decomposition (thermolysis) of Cd thiolates precursors embedded in a polymer
      matrix and the nucleation of CdS nanoparticles. A thiolate precursor/polymer
      solid foil was heated to 300 degrees C in the X-ray diffraction setup of beamline
      W1.1 at Hasylab, and the diffraction curves were each recorded at 10 degrees C.
      At temperatures above 240 degrees C, the precursor decomposition is complete and
      CdS nanoparticles grow within the polymer matrix forming a nanocomposite with
      interesting optical properties. The nanoparticle structural properties (size and
      crystal structure) depend on the annealing temperature. Transmission electron
      microscopy (TEM) and photoluminescence (PL) analyses were used to characterize
      the nanoparticles. A possible mechanism driving the structural transformation of
      the precursor is inferred from the diffraction features arising at the different
      temperatures.

PMID- 16800591
TI  - Role of O2 in inducing intensive fluctuations of surface-enhanced Raman
      scattering spectra.
AB  - Confocal Raman microscopic measurements were performed on silver electrodes
      covered with hydrogenated amorphous carbon (a-C:H). When short accumulation time
      was used, the subsequently measured surface-enhanced Raman scattering (SERS)
      spectra exhibited fluctuations. As previously reported for other systems, the
      intensity of fluctuations of SERS spectra significantly decreases if O2 was
      removed from the ambient medium. In this contribution we show that intensive SERS
      fluctuations can be also observed for a-C:H/Ag samples immersed in the
      deoxygenated electrolyte after applying a negative potential pulse to the silver
      electrode. It means that the O2-mediated Burstein mechanism of SERS fluctuations,
      which has been previously proposed to explain the SERS O2 effect, is not adequate
      for these results. We suggest that oxygen chemisorbed on the silver surface
      decreases the average strength of the interaction between a-C:H clusters and the
      metal surface (and hence the speed of movement of a-C:H clusters across the metal
      surface) and that the SERS O2 effect should be rather explained using the
      "classical" model of SERS fluctuations, in which fluctuations are interpreted as
      a result of the thermally activated diffusion of carbon segments in and out of
      the SERS "hot spots". A numerical algorithm for modeling of the fluctuations of
      SERS intensity has been proposed, and some example simulations of SERS
      fluctuations have been carried out. For the first time, strongly fluctuating
      bands due to the stretching vibrations of significantly weakened C-H bonds have
      been identified.

PMID- 16800592
TI  - Imaging of atomic layer deposited (ALD) tungsten monolayers on alpha-TiO2(110) by
      X-ray standing wave Fourier inversion.
AB  - A single atomic layer of tungsten grown by atomic layer deposition (ALD) on a
      single-crystal rutile TiO2(110) support is studied by the X-ray standing wave
      (XSW) technique. The surface structural and chemical properties were also
      examined using atomic force microscopy, X-ray photoelectron spectroscopy, and low
      energy electron diffraction. The XSW measured set of hkl Fourier components for
      the W atomic distribution function are summed together to produce a model
      independent 3D map of the W atoms relative to the rutile lattice. The 3D atomic
      image shows surface tungsten atoms equally occupying the two nonequivalent Ti
      sites with a slight outward displacement. This corresponds to the atop and bridge
      sites with respect to the underlying lattice oxygen atoms. These XSW measurements
      clearly show that ALD conformal layers can be highly coherent with respect to the
      substrate lattice.

PMID- 16800594
TI  - Structures and reaction mechanisms of cumene formation via benzene alkylation
      with propylene in a newly synthesized ITQ-24 zeolite: an embedded ONIOM study.
AB  - The cumene formation via benzene alkylation with propylene on the new three
      dimensional nanoporous catalyst, ITQ-24 zeolite, has been investigated by using
      the ONIOM2(B3LYP/6-31G(d,p):UFF) method. Both consecutive and associative
      reaction pathways are examined. The contributions of the short-range van der
      Waals interactions, which are explicitly included in the ONIOM2 model, and an
      additional long-range electrostatic potential from the extended zeolite framework
      to the energy profile are taken into consideration. It is found that benzene
      alkylation with propylene in the ITQ-24 zeolite prefers to occur through the
      consecutive reaction mechanism. The benzene alkylation step is the reaction rate
      determining step with an estimated activation energy of 35.70 kcal/mol,
      comparable with an experimental report in beta-zeolite of 34.9 kcal/mol. The
      electrostatic potential from the extended zeolite framework shows a much more
      significant contribution to the transition state selectivity than the van der
      Waals interactions.

PMID- 16800593
TI  - Direct measurements of interactions between polypeptides and carbon nanotubes.
AB  - The interactions of various polypeptides with individual carbon nanotubes (CNTs),
      both multiwall (MW) and single wall (SW), were investigated by atomic force
      microscopy (AFM). While adhesion forces arising from electrostatic attraction
      interactions between the protonated amine groups of polylysine and carboxylic
      groups on the acid-oxidized multi-wall carbon nanotubes (Ox-MWCNTs) dominate the
      interaction at a low pH, weaker adhesion forces via the hydrogen bonding between
      the neutral -NH2 groups of polylysine and -COO- groups of the Ox-MWCNTs were
      detected at a high pH. The adhesion force was further found to increase with the
      oxidation time for Ox-MWCNTs and to be negligible for oxidized single-wall carbon
      nanotubes (Ox-SWCNTs) because carboxylate groups were only attached onto the
      nanotube tips in the latter whereas onto both the nanotube tips and sidewall in
      the former. Furthermore, it was demonstrated that proteins containing aromatic
      moieties, such as polytryptophan, showed a stronger adhesion force with Ox-MWCNTs
      than that of polylysine because of the additional pi-pi stacking interaction
      between the polytryptophan chains and CNTs.

PMID- 16800595
TI  - Dissociative electron transfer in donor-peptide-acceptor systems: results for
      kinetic parameters from a density functional/polarizable continuum model.
AB  - The main structural and electronic factors playing a role in intramolecular
      dissociative electron transfer of a simple donor-peptide-acceptor (D-peptide-A)
      model have been investigated by an integrated computational protocol based on the
      density functional theory, its time-dependent extension, and the polarizable
      continuum model. Our results allow us to elucidate the electronic states involved
      in the process and how they are perturbed by the orientation of the donor and the
      acceptor with respect to the peptide chain and by the presence of the solvent. We
      also report a semiquantitative estimation of the rate constant governing electron
      transfer obtained by a direct quantum mechanical evaluation of all the terms
      entering the kinetic expressions based on the Marcus theory and its extensions.

PMID- 16800596
TI  - The body-centered cubic structure of methyllithium tetramer crystal: staggered
      methyl conformation by electrostatic stabilization via intratetramer
      multipolarization.
AB  - The methyllithium tetramer (CH3Li)4 structure in the bcc crystal has been
      theoretically optimized with the use of density functional theory calculations
      under the periodic boundary condition. The X-ray structure shows that the methyl
      group conformation in tetramer in crystal takes the staggered form rather than
      the eclipsed form that is taken in the isolated tetramer, i.e., the crystal
      packing effect, and this has been reproduced for the first time. It is concluded
      that the staggered form is advantageous in crystal, as a whole, due to the larger
      electrostatic stabilization via the induced intratetramer multipolarization,
      although it should cause, simultaneously, smaller destabilization in
      intratetramer electronic energy.

PMID- 16800597
TI  - Mechanistic aspects of homogeneous and heterogeneous melting processes.
AB  - Molecular dynamics simulations have been employed to explore the response of
      crystalline Ar systems with and without a free surface to a gradual temperature
      rise. The surface-free crystalline bulk undergoes a homogeneous melting process
      at the limit of superheating, whereas the semicrystal terminating with a free
      plane surface melts with a heterogeneous mechanism at a temperature corresponding
      to the equilibrium melting point. Numerical findings suggest that the gradual
      disordering of the crystalline lattice as well as the homogeneous and
      heterogeneous melting processes are mediated by atoms with defective
      coordination. Their concentration in the regions close to the semicrystal surface
      at the equilibrium melting point is found to be approximately the same as in the
      surface-free bulk at the limit of superheating.

PMID- 16800598
TI  - New insights on anion recognition by isomers of a calix pyrrole derivative.
AB  - Two isomeric structures of meso-tetramethyltetrakis(3
      hydroxyphenyl)calix[4]pyrrole, 4-alphaalpha betabeta and 4-alphabeta alphabeta,
      have been isolated and characterized by 1H NMR in different solvents (CD3CN,
      CD3OD, and DMSO-d6) at 298 K. Standard Gibbs energies of solution derived from
      solubility data in various solvents were used to calculate the transfer Gibbs
      energy, delta(t)G(o), of these ligands using acetonitrile as the reference
      solvent. These results are consistent with the 1H NMR studies in different media
      that show chemical shift changes observed in the resonances of the NH and the OH
      protons of these ligands. Solvate formation was observed when these isomers were
      exposed to saturated atmosphere of N,N-dimethylformamide, dimethyl sulfoxide and
      propylene carbonate. Anion interaction involving 4-alphaalpha betabeta and 4
      alphabeta alphabeta was investigated by 1H NMR in CD3CN while the complex
      composition was assessed through conductance measurements. Significant
      differences are observed in the affinity of these ligands for anions as well as
      in the composition of the fluoride complexes. Thus 4-alphaalpha betabeta shows
      selectivity for H2PO4(-) in acetonitrile while its isomer 4-alphabeta alphabeta
      is selective for the fluoride anion. Again the complex composition is altered for
      the fluoride anion when complexed with 4-alphaalpha betabeta in acetonitrile (1:1
      complex) relative to 4-alphabeta alphabeta in the same solvent. The latter isomer
      shows an enhanced hosting ability for this anion. Thus two anions are taken up
      per unit of ligand. The thermodynamics of complexation of H2PO4(-) and these
      ligands in acetonitrile is discussed, and the results are compared with those
      involving calix[4]pyrrole and this anion in this solvent. It is shown that the
      isomers interact with two H2PO4(-) anions while one calix[4]pyrrole unit
      interacts with this anion. This paper demonstrates for the first time that the
      enthalpy parameter may be a suitable reporter of the number of hydrogen bonds
      formed when calix[4]pyrrole and its derivatives interact with the dihydrogen
      phosphate anion in acetonitrile. In moving from acetonitrile to N,N
      dimethylformamide, 4-alphaalpha betabeta is unable to enter complexation with
      most anions, except fluoride, with which the formation of a 1:2 (ligand:anion)
      complex is demonstrated. The rather versatile behavior of these receptors for
      anions is explained on the basis of 1H NMR evidence and solvation effects. These
      investigations highlight the importance of the medium effect on the stability of
      the complex and reflect the inherent nature of the solvent and its highly
      significant involvement in the complexation process.

PMID- 16800599
TI  - Nonionic urea surfactants: formation of inverse hexagonal lyotropic liquid
      crystalline phases by introducing hydrocarbon chain unsaturation.
AB  - The homo-interaction between urea moieties residing in close proximity to each
      other generally results in very strong intermolecular hydrogen bonding. The
      bifurcated hydrogen bonding exhibited by n-alkyl substituted ureas means that for
      those urea surfactants possessing medium and long hydrocarbon chain substituents
      the crystal to isotropic liquid melting point is high and the solubility in water
      is very low, compared to other similar chain length nonionic surfactants. In
      addition, saturated n-alkyl urea surfactants do not form lyotropic liquid
      crystalline phases in water. In this work the strong intermolecular hydrogen
      bonding of the urea headgroup has been ameliorated through the introduction of
      unsaturated hydrocarbon chains, viz., oleyl (cis-octadec-9-enyl), linoleyl (cis,
      cis-octadec-9,12-dienyl), and linolenyl (cis, cis, cis-octadec-9,12,15-trienyl)
      with one, two, and three carbon double bonds, respectively. Unsaturation in the
      C18 urea surfactants lowers the melting point and promotes an inverse hexagonal
      phase, in oleyl urea-water and linoleyl urea-water systems, which is
      thermodynamically stable in excess water. As the degree of unsaturation is
      increased to three in linolenyl urea, there is a tendency for
      autoxidation/polymerization. The occurrence of an inverse hexagonal phase in the
      nonionic urea surfactant-water systems has been rationalized in terms of both
      local molecular and global self-assembled aggregate packing constraints.

PMID- 16800600
TI  - Molecular simulation and experimental study of substituted polyacetylenes:
      fractional free volume, cavity size distributions and diffusion coefficients.
AB  - Glassy, disubstituted acetylene-based polymers exhibit extremely high gas
      permeabilities and high vapor/gas selectivities, which is quite unusual for
      conventional glassy polymers such as polysulfone. Diffusion coefficients of
      poly[1-phenyl-2-[p-(trimethylsilyl)phenyl]acetylene] (PTMSDPA) and
      poly[diphenylacetylene] (PDPA) were obtained using both molecular simulation and
      experimental techniques. PTMSDPA, a disubstituted glassy acetylene-based polymer,
      exhibits higher diffusivity than its desilylated analogue, PDPA. Simulation
      results are in good agreement with experimental data. Cavity size (free volume)
      distributions of both polymers are also obtained using an energetic-based
      algorithm (in't Veld et al., J. Phys. Chem. B 2000, 104, 12028) developed
      recently. Larger cavities in PTMSDPA contribute to its higher diffusivity, and
      higher permeability.

PMID- 16800601
TI  - Structures of DNA-linked nanoparticle aggregates.
AB  - The room-temperature structure of DNA-linked gold nanoparticle aggregates is
      investigated using a combination of experiment and theory. The experiments
      involve extinction spectroscopy measurements and dynamic light scattering
      measurements of aggregates made using 60 and 80 nm gold particles and 30 base
      pair DNA. The theoretical studies use calculated spectra for models of the
      aggregate structures to determine which structure matches the observations. These
      models include diffusion-limited cluster-cluster aggregation (DLCA), reaction
      limited cluster-cluster aggregation (RLCA), and compact (nonfractal) cluster
      aggregation. The diameter of the nanoparticles used in the experiments is larger
      than has been considered previously, and this provides greater sensitivity of
      spectra to aggregate structure. We show that the best match between experiment
      and theory occurs for the RLCA fractal structures. This indicates that DNA
      hybridization takes place under irreversible conditions in the room-temperature
      aggregation. Some possible structural variations which might influence the result
      are considered, including the edge-to-edge distance between nanoparticles,
      variation in the diameter of the nanoparticles, underlying lattice structures of
      on-lattice compact clusters, and positional disorders in the lattice structures.
      We find that these variations do not change the conclusion that the room
      temperature structure of the aggregates is fractal. We also examine the variation
      in extinction at 260 nm as temperature is increased, showing that the decrease in
      extinction at temperatures below the melting temperature is related to a
      morphological change from fractal toward compact structures.

PMID- 16800602
TI  - Dielectric response of imidazolium-based room-temperature ionic liquids.
AB  - We have used microwave dielectric relaxation spectroscopy to study the picosecond
      dynamics of five low-viscosity, highly conductive room temperature ionic liquids
      based on 1-alkyl-3-methylimidazolium cations paired with the
      bis((trifluoromethyl)sulfonyl)imide anion. Up to 20 GHz the dielectric response
      is bimodal. The longest relaxation component at the time scale of several 100 ps
      reveals strongly nonexponential dynamics and correlates with the viscosity in a
      manner consistent with hydrodynamic predictions for the diffusive reorientation
      of dipolar ions. Methyl substitution at the C2 position destroys this
      correlation. The time constants of the weak second process at the 20 ps time
      scale are practically the same for each salt. This intermediate process seems to
      correlate with similar modes in optical Kerr effect spectra, but its physical
      origin is unclear. The missing high-frequency portion of the spectra indicates
      relaxation beyond the upper cutoff frequency of 20 GHz, presumably due to
      subpicosecond translational and librational displacements of ions in the cage of
      their counterions. There is no evidence for orientational relaxation of long
      lived ion pairs.

PMID- 16800603
TI  - One-dimensional free-energy profiles of complex systems: progress variables that
      preserve the barriers.
AB  - We show that the balanced minimum-cut procedure introduced in PNAS 2004, 101,
      14766 can be reinterpreted as a method for solving the constrained optimization
      problem of finding the minimum cut among the cuts with a particular value of an
      additive function of the nodes on either side of the cut. Such an additive
      function (e.g., the partition function of the reactant region) can be used as a
      progress coordinate to determine a one-dimensional profile (FEP) of the free
      energy surface of the protein-folding reaction as well as other complex
      reactions. The algorithm is based on the network (obtained from an equilibrium
      molecular dynamics simulation) that represents the calculated reaction behavior.
      The resulting FEP gives the exact values of the free energy as a function of the
      progress coordinate; i.e., at each value of the progress coordinate, the profile
      is obtained from the surface with the minimal partition function among the
      surfaces that divide the full free-energy surface between two chosen end points.
      In many cases, the balanced minimum-cut procedure gives results for only a
      limited set of points. An approximate method based on p(fold) is shown to provide
      the profile for a more complete set of values of the progress coordinate.
      Applications of the approach to model problems and to realistic systems (beta
      hairpin of protein G, LJ38 cluster) are presented.

PMID- 16800604
TI  - Ab initio molecular dynamics study of a mixture of HF(aq) and HCl(aq).
AB  - We have studied a mixture of HF and HCl molecules in water using Car-Parrinello
      ab initio molecular dynamics (CPMD). We have done simulations with 1 HF and 3 HCl
      molecules, 3 HF and 4 HCl, 6 HF and 8 HCl (6/8 simulation), and 14 HF molecules.
      All simulations consist of 32 molecules, and they were 10-96 ps long. The HF
      dissociation probability was around 30%, and HCl's was more than 90%. The
      solvation of the HF molecule was much better than the solvation of HCl. The
      solvation environment of F, both the F- ion and the F in HF, did not depend much
      on the acids concentration, whereas the Cl coordination numbers were rather
      sensitive to the concentration. In the 6/8 simulation, all XH-Y (X, Y = F, Cl)
      type molecules were observed and the FH-F was the most probable. In general, the
      molecular structures in mixed aqueous acid systems were similar to the pure
      HF(aq) and HCl(aq) systems.

PMID- 16800605
TI  - The Kirkwood-Buff theory of solutions and the local composition of liquid
      mixtures.
AB  - The present paper is devoted to the local composition of liquid mixtures
      calculated in the framework of the Kirkwood-Buff theory of solutions. A new
      method is suggested to calculate the excess (or deficit) number of various
      molecules around a selected (central) molecule in binary and multicomponent
      liquid mixtures in terms of measurable macroscopic thermodynamic quantities, such
      as the derivatives of the chemical potentials with respect to concentrations, the
      isothermal compressibility, and the partial molar volumes. This method accounts
      for an inaccessible volume due to the presence of a central molecule and is
      applied to binary and ternary mixtures. For the ideal binary mixture it is shown
      that because of the difference in the volumes of the pure components there is an
      excess (or deficit) number of different molecules around a central molecule. The
      excess (or deficit) becomes zero when the components of the ideal binary mixture
      have the same volume. The new method is also applied to methanol + water and 2
      propanol + water mixtures. In the case of the 2-propanol + water mixture, the new
      method, in contrast to the other ones, indicates that clusters dominated by 2
      propanol disappear at high alcohol mole fractions, in agreement with experimental
      observations. Finally, it is shown that the application of the new procedure to
      the ternary mixture water/protein/cosolvent at infinite dilution of the protein
      led to almost the same results as the methods involving a reference state.

PMID- 16800606
TI  - Analysis on solvated molecules with a new energy partitioning scheme for intra-
      and intermolecular interactions.
AB  - A new partitioning scheme for the total energy of molecules is presented. In the
      scheme, the Hartree-Fock total energy of a molecular system is represented as the
      sum of one- and two-center terms exactly. The present method provides physically
      reasonable behavior for a wide range of interactions, and intermolecular
      interaction is treated equivalently with intramolecular interaction. The method
      is applied to analysis on the inter- and intramolecular interactions of molecular
      complexes both in gas phase and in aqueous solution. The results strongly
      indicate that the present method is a powerful tool to understand not only the
      bonding nature of molecules but also interaction between molecules.

PMID- 16800607
TI  - Effect of added free polymer on the swelling of neutral microgel particles: a
      thermodynamic approach.
AB  - Microgel particles based on poly (N-isopropylacrylamide) have been shown to
      display an initial swelling behavior, followed by a collapse, with increasing
      concentration of added poly(ethylene oxide), PEO, chains. This paper considers
      the thermodynamic reasons for the observed expansion and subsequent shrinkage of
      the particles. At low concentrations of PEO, the free chains permeate into the
      microgel particles and cause an increase in osmotic pressure, expanding the
      particles. At higher concentrations of PEO, the particles are saturated and an
      increase in osmotic pressure in the external phase causes the particles to
      collapse again. The calculated magnitude of swelling and the effect of PEO
      molecular weight are, at least qualitatively, in agreement with the experimental
      observations reported elsewhere.

PMID- 16800608
TI  - Role of crystal-amorphous interaction in phase equilibria of crystal-amorphous
      polymer blends.
AB  - A self-consistent theory has been developed for determination of phase diagrams
      of a crystalline polymer solution. Although the original Flory diluent theory
      captures the liquidus line, the theory is incapable of accounting for the solidus
      line due to the inherent assumption of complete immiscibility of solvent in the
      solid crystal. The present theory considers all possible interactions involving
      amorphous-amorphous and crystal-amorphous interactions. The self-consistent
      solutions predict various phase diagrams involving liquid-liquid, pure solid, and
      liquid-solid coexistence regions bound by liquidus and solidus lines. In the
      limit of complete insolubility of solvent in neat solid crystal, the original
      Flory diluent theory is recovered.

PMID- 16800609
TI  - Thermodynamics for single-molecule stretching experiments.
AB  - We show how to construct nonequilibrium thermodynamics for systems too small to
      be considered thermodynamically in a traditional sense. Through the use of a
      nonequilibrium ensemble of many replicas of the system which can be viewed as a
      large thermodynamic system, we discuss the validity of nonequilibrium
      thermodynamics relations and analyze the nature of dissipation in small systems
      through the entropy production rate. We show in particular that the Gibbs
      equation, when formulated in terms of average values of the extensive quantities,
      is still valid, whereas the Gibbs-Duhem equation differs from the equation
      obtained for large systems due to the lack of the thermodynamic limit. Single
      molecule stretching experiments are interpreted under the prism of this theory.
      The potentials of mean force and mean position, now introduced in these
      experiments in substitution of the thermodynamic potentials, correspond
      respectively to our Helmholtz and Gibbs energies. These results show that a
      thermodynamic formalism can indeed be applied at the single-molecule level.

PMID- 16800610
TI  - Repair reactions of pyrimidine-derived radicals by aliphatic thiols.
AB  - Pyrimidinyl radicals of various structures (Pyr*) were generated in aqueous and
      alcohol-containing solutions by means of pulse radiolysis to determine the rate
      constants of their repair reactions by different thiols (RSH = cysteamine, 2
      mercaptoethanol, cysteine, and penicillamine): Pyr* + RSH --> PyrH + RS*. C5-OH
      and C6-OH adduct radicals of the pyrimidines react with thiols with k9 = (1.2
      10.0) x 10(6) dm3 mol(-1) s(-1). Similar repair rate constants were found for
      uracil- and thymine-derived N1-centered radicals, k31 = (1.5-6.1) x 10(6) dm3
      mol(-1) s(-1). However, pyrimidine radical anions protonated at their C6 position
      and C6-uracilyl radicals, with carbonyl groups at their C5 position, react with
      thiols faster, with k24 = (0.5-7.6) x 10(7) dm3 mol(-1) s(-1) and k14 = (1.4-4.8)
      x 10(7) dm3 mol(-1) s(-1), respectively. Quantum chemical calculations, at the
      B3LYP/6-31G(d,p) and self-consistent reaction field polarizable continuum model
      level point to the combined effects of the energy gap between interacting
      molecular orbitals, charge distribution within different pyrimidine-derived
      radicals, and the coefficients of the atomic orbitals as the possible reasons for
      the differences in the rate constants of repair.

PMID- 16800611
TI  - A hybrid deterministic-stochastic algorithm for modeling cell signaling dynamics
      in spatially inhomogeneous environments and under the influence of external
      fields.
AB  - Cell signaling dynamics mediate myriad processes in biology. It has become
      increasingly clear that inter- and intracellular signaling reactions often occur
      in a spatially inhomogeneous environment and that it is important to account for
      stochastic fluctuations of certain species involved in signaling reactions. The
      importance of these effects enhances the difficulty of gleaning mechanistic
      information from observations of a few experimental reporters and highlights the
      significance of synergistic experimental and computational studies. When both
      stochastic fluctuations and spatial inhomogeneity must be included in a model
      simultaneously, however, the resulting computational demands quickly become
      overwhelming. In many situations the failure of standard coarse-graining methods
      (i.e., ignoring spatial variation or stochastic fluctuations) when applied to all
      components of a complex system does not exclude the possibility of successfully
      applying such coarse-graining to some components of the system. Following this
      approach alleviates computational cost but requires "hybrid" algorithms where
      some variables are treated at a coarse-grained level while others are not. We
      present an efficient algorithm for simulation of stochastic, spatially
      inhomogeneous reaction-diffusion kinetics coupled to coarse-grained fields
      described by (stochastic or deterministic) partial differential equations (PDEs).
      The PDEs could represent mean-field descriptions of reactive species present in
      large copy numbers or evolution of hydrodynamic variables that influence
      signaling (e.g., membrane shape or cytoskeletal motion). We discuss the
      approximations made to derive our algorithm and test its efficacy by applying it
      to problems that include many features typical of realistic cell signaling
      processes.

PMID- 16800612
TI  - Ultrafast heme dynamics in ferrous versus ferric cytochrome c studied by time
      resolved resonance Raman and transient absorption spectroscopy.
AB  - Cytochrome c (Cyt c) is a heme protein involved in electron transfer and also in
      apoptosis. Its heme iron is bisaxially ligated to histidine and methionine side
      chains and both ferric and ferrous redox states are physiologically relevant, as
      well as a ligand exchange between internal residue and external diatomic
      molecule. The photodissociation of internal axial ligand was observed for several
      ferrous heme proteins including Cyt c, but no time-resolved studies have been
      reported on ferric Cyt c. To investigate how the oxidation state of the heme
      influences the primary photoprocesses, we performed a comprehensive comparative
      study on horse heart Cyt c by subpicosecond time-resolved resonance Raman and
      femtosecond transient absorption spectroscopy. We found that in ferric Cyt c, in
      contrast to ferrous Cyt c, the photodissociation of an internal ligand does not
      take place, and relaxation dynamics is dominated by vibrational cooling in the
      ground electronic state of the heme. The intermolecular vibrational energy
      transfer was found to proceed in a single phase with a temperature decay of
      approximately 7 ps in both ferric and ferrous Cyt c. For ferrous Cyt c, the
      instantaneous photodissociation of the methionine side chain from the heme iron
      is the dominant event, and its rebinding proceeds in two phases, with time
      constants of approximately 5 and approximately 16 ps. A mechanism of this process
      is discussed, and the difference in photoinduced coordination behavior between
      ferric and ferrous Cyt c is explained by an involvement of the excited electronic
      state coupled with conformational relaxation of the heme.

PMID- 16800613
TI  - Decomposition of the solvation free energies of deoxyribonucleoside triphosphates
      using the free energy perturbation method.
AB  - Free energy perturbation (FEP) calculations using the Amber 95 force field and
      the TIP3P water model were carried out to evaluate the solvation free energy of
      deoxyribonucleoside triphosphates in aqueous solution. Solvation free energies of
      -307.5, -311.5, -314.1, and -317.0 kcal/mol were calculated for the (Mg x dTTP)2
      , (Mg x dATP)2-, (Mg x dCTP)2-, and (Mg x dGTP)2- complexes, respectively.
      Structural origins of the relative solvation free energies of deoxyribonucleoside
      phosphates were examined by calculating the contribution of the interaction of
      the base moiety with its surroundings. We showed that for each nucleobase the
      magnitude of this contribution is unaffected by substituting the 5'-OH group of
      the corresponding nucleoside with the charged mono- or triphosphate groups. This
      free energy contribution was further decomposed into the sum of free energies
      originating from the interactions of the base with itself, its substituent,
      water, and Na+ ions. Although the sum of these components was nearly constant
      over a wide range of solutes the individual free energy constituents varied
      significantly. Furthermore, this decomposition showed a high degree of
      additivity. Computational conditions necessary for obtaining additive free energy
      decomposition for the systems studied here within the framework of the FEP method
      included the use of a single mutation pathway and a subdivision of the FEP
      protocol into 51 or more windows.

PMID- 16800614
TI  - Steered molecular dynamics simulations of Na+ permeation across the gramicidin A
      channel.
AB  - The potential of mean forces (PMF) governing Na+ permeation through gramicidin A
      (gA) channels with explicit water and membrane was characterized using steered
      molecular dynamics (SMD) simulations. Constant-force SMD with a steering force
      parallel to the channel axis revealed at least seven energy wells in each monomer
      of the channel dimer. Except at the channel dimer interface, each energy well is
      associated with at least three and at most four backbone carbonyl oxygens and two
      water oxygens in a pseudo-hexahedral or pseudo-octahedral coordination with the
      Na+ ion. Repeated constant-velocity SMD by dragging a Na+ ion from each energy
      well in opposite directions parallel to the channel axis allowed the computation
      of the PMF across the gA channel, revealing a global minimum corresponding to Na+
      binding sites near the entrance of gA at +/-9.3 A from the geometric center of
      the channel. The effect of volatile anesthetics on the PMF was also analyzed in
      the presence of halothane molecules. Although the accuracy of the current PMF
      calculation from SMD simulations is not yet sufficient to quantify the PMF
      difference with and without anesthetics, the comparison of the overall PMF
      profiles nevertheless confirms that the anesthetics cause insignificant changes
      to the structural makeup of the free energy wells along the channel and the
      overall permeation barrier. On average, the PMF appears less rugged in the outer
      part of the channel in the presence of anesthetics, consistent with our earlier
      finding that halothane interaction with anchoring residues makes the gA channel
      more dynamic. A causal relationship was observed between the reorientation of the
      coordinating backbone carbonyl oxygen and Na+ transit from one energy well to
      another, suggesting the possibility that even minute changes in the conformation
      of pore-lining residues due to dynamic motion could be sufficient to trigger the
      ion permeation. Because some of the carbonyl oxygens contribute to Na+
      coordination in two adjacent energy wells, our SMD results reveal that the atomic
      picture of ion "hopping" through a gA channel actually involves a Na+ ion being
      carried in a relay by the coordinating oxygens from one energy well to the next.
      Steered molecular dynamics complements other computational approaches as an
      attractive means for the atomistic interpretation of experimental permeation
      studies.

PMID- 16800615
TI  - Molecular dynamics of apo-adenylate kinase: a principal component analysis.
AB  - Adenylate kinase from E. coli (AKE) is studied with molecular dynamics. AKE
      undergoes large-scale motions of its Lid and AMP-binding domains when its open
      form closes over its substrates, AMP and Mg2+-ATP. The third domain, the Core, is
      relatively stable during closing. The resulting trajectory is analyzed with a
      principal component analysis method that decomposes the atom motions into modes
      ordered by their decreasing contributions to the total protein fluctuation.
      Simulations at 303 K (normal T) and 500 K (high T) reveal that at both
      temperatures the first three modes account for 70% of the total fluctuation. The
      residues that contribute the most to these three modes are concentrated in the
      Lid and AMP-binding domains. Analysis of the normal T modes indicates that the
      Lid and AMP-binding domains sample a broad distribution of conformations
      indicating that AKE is designed to provide its substrates with a large set of
      conformations. The high T results show that the Lid initially closes toward the
      Core. Subsequently, the Lid rotates to a new stable conformation that is
      different from what is observed in the substrate-bound AKE. These results are
      discussed in the context of experimental data that indicate that adenylate
      kinases do sample more than one conformational state in solution and that each of
      these conformational states undergoes substantial fluctuations. A pair of
      residues is suggested for labeling that would be useful for monitoring distance
      fluctuations by energy transfer experiments.

PMID- 16800616
TI  - Intra- and intermolecular heavy-atom effects on the fluorescence properties of
      brominated C60 polyads.
AB  - A series of brominated mono-methano[60]fullerene malonate derivatives (two diads
      and one triad) are investigated for intramolecular and external heavy-atom
      effects on their fluorescence. Significant internal and external heavy-atom
      effects are observed in the three cases. It is shown that the internal effect
      doubles when going from the diads to the triad. In bromobenzene and in
      iodobenzene, the external effect is predominant, and diads and triad behave
      identically.

PMID- 16800617
TI  - The application of Shannon's measure of information for a complex chemical
      system.
AB  - Information theory and, specifically, Shannon's measure of information is used to
      compare the interaction parameters (beta) in regular solution theory (RST) and
      Ingram's model for the mixture of cetyltrimethylammonium bromide (CTAB) and
      Triton X-100 (TX100). Results show that beta values from regular solution theory
      are more accurate than those of Ingram's model. Additionally, the procedure
      applied in this paper for the calculation of uncertainties in the continuous
      case, prevents difficulties concerning differential entropy.

PMID- 16800618
TI  - Generalization of the friction theory for viscosity modeling.
AB  - The friction theory (FT) approach relates the viscosity of a fluid to its
      equation of state (EoS), and it is known to give good results for a large number
      of compounds over wide ranges of temperature and pressure. Previous FT versions
      were restricted to use EoS of the van der Waals type, i.e., EoS explicitly
      consisting of a repulsive and an attractive term, which limited the number of
      usable EoS as well as the accuracy of the viscosity predictions. In this work,
      the restriction is removed by means of a pragmatic generalized definition of
      repulsive and attractive terms based on the internal pressure concept. As a
      result, the FT theory can be extended to practically all types of EoS, from
      theoretical ones (e.g., EoS based on thermostatistical or renormalization
      theories) to the highly accurate empirical reference EoS. In combination with the
      later, the FT is shown to represent experimental viscosity data for several
      fluids, including water, with an accuracy as high as that required for reference
      models. Additionally, some relevant phenomena, such as the critical anomaly,
      appear to follow naturally from the physics already built into the EoS.

PMID- 16800619
TI  - The gamma-secretase complex: membrane-embedded proteolytic ensemble.
AB  - Gamma-secretase is responsible for the proteolytic processing of a variety of
      membrane-associated fragments derived from type I integral membrane proteins,
      including the amyloid beta-protein precursor and the Notch receptor. This enzyme
      is composed of four different integral membrane proteins: presenilin, nicastrin,
      Aph-1, and Pen-2. During assembly and maturation of the protease complex,
      presenilin is endoproteolyzed into two subunits, each of which contributes one
      aspartate to the active site of an aspartyl protease. Substrate apparently
      interacts with an initial docking site before passing in whole or in part between
      the two presenilin subunits to the internal water-containing active site. The
      ectodomain of nicastrin also interacts with the N-terminus of the substrate as an
      essential step in substrate recognition and processing. Sites for allosteric
      regulation on the protease complex allow selective inhibition or modulation of
      APP processing without interfering with Notch signaling, and such selective
      agents may represent promising leads for the development of Alzheimer's disease
      therapeutics. Elucidation of detailed structural features of gamma-secretase and
      other membrane-embedded proteases is the next frontier in understanding how these
      enzymes carry out hydrolysis within the lipid bilayer.

PMID- 16800620
TI  - Mechanistic inferences from the binding of ligands to LpxC, a metal-dependent
      deacetylase.
AB  - The metal-dependent deacetylase LpxC catalyzes the first committed step of lipid
      A biosynthesis in Gram-negative bacteria. Accordingly, LpxC is an attractive
      target for the development of inhibitors that may serve as potential new
      antibiotics for the treatment of Gram-negative bacterial infections. Here, we
      report the 2.7 A resolution X-ray crystal structure of LpxC complexed with the
      substrate analogue inhibitor TU-514 and the 2.0 A resolution structure of LpxC
      complexed with imidazole. The X-ray crystal structure of LpxC complexed with TU
      514 allows for a detailed examination of the coordination geometry of the
      catalytic zinc ion and other enzyme-inhibitor interactions in the active site.
      The hydroxamate group of TU-514 forms a bidentate chelate complex with the zinc
      ion and makes hydrogen bond interactions with conserved active site residues E78,
      H265, and T191. The inhibitor C-4 hydroxyl group makes direct hydrogen bond
      interactions with E197 and H58. Finally, the C-3 myristate moiety of the
      inhibitor binds in the hydrophobic tunnel of the active site. These
      intermolecular interactions provide a foundation for understanding structural
      aspects of enzyme-substrate and enzyme-inhibitor affinity. Comparison of the TU
      514 complex with cacodylate and imidazole complexes suggests a possible substrate
      diphosphate binding site and highlights residues that may stabilize the
      tetrahedral intermediate and its flanking transition states in catalysis.
      Evidence of a catalytic zinc ion in the native zinc enzyme coordinated by H79,
      H238, D242, and two water molecules with square pyramidal geometry is also
      presented. These results suggest that the native state of this metallohydrolase
      may contain a pentacoordinate zinc ion, which contrasts with the native states of
      archetypical zinc hydrolases such as thermolysin and carboxypeptidase A.

PMID- 16800621
TI  - Electrostatic environment of hemes in proteins: pK(a)s of hydroxyl ligands.
AB  - The pK(a)s of ferric aquo-heme and aquo-heme electrochemical midpoints (E(m)s) at
      pH 7 in sperm whale myoglobin, Aplysia myoblogin, hemoglobin I, heme oxygenase 1,
      horseradish peroxidase and cytochrome c oxidase were calculated with Multi
      Conformation Continuum Electrostatics (MCCE). The pK(a)s span 3.3 pH units from
      7.6 in heme oxygenase 1 to 10.9 in peroxidase, and the E(m)s range from -250 mV
      in peroxidase to 125 mV in Aplysia myoglobin. Proteins with higher in situ ferric
      aquo-heme pK(a)s tend to have lower E(m)s. Both changes arise from the protein
      stabilizing a positively charged heme. However, compared with values in solution,
      the protein shifts the aquo-heme E(m)s more than the pK(a)s. Thus, the protein
      has a larger effective dielectric constant for the protonation reaction, showing
      that electron and proton transfers are coupled to different conformational
      changes that are captured in the MCCE analysis. The calculations reveal a
      breakdown in the classical continuum electrostatic analysis of pairwise
      interactions. Comparisons with DFT calculations show that Coulomb's law
      overestimates the large unfavorable interactions between the ferric water-heme
      and positively charged groups facing the heme plane by as much as 60%. If
      interactions with Cu(B) in cytochrome c oxidase and Arg 38 in horseradish
      peroxidase are not corrected, the pK(a) calculations are in error by as much as 6
      pH units. With DFT corrected interactions calculated pK(a)s and E(m)s differ from
      measured values by less than 1 pH unit or 35 mV, respectively. The in situ aquo
      heme pK(a) is important for the function of cytochrome c oxidase since it helps
      to control the stoichiometry of proton uptake coupled to electron transfer [Song,
      Michonova-Alexova, and Gunner (2006) Biochemistry 45, 7959-7975].

PMID- 16800622
TI  - Calculated proton uptake on anaerobic reduction of cytochrome C oxidase: is the
      reaction electroneutral?
AB  - Cytochrome c oxidase is a transmembrane proton pump that builds an
      electrochemical gradient using chemical energy from the reduction of O(2).
      Ionization states of all residues were calculated with Multi-Conformation
      Continuum Electrostatics (MCCE) in seven anaerobic oxidase redox states ranging
      from fully oxidized to fully reduced. One long-standing problem is how proton
      uptake is coupled to the reduction of the active site binuclear center (BNC). The
      BNC has two cofactors: heme a(3) and Cu(B). If the protein needs to maintain
      electroneutrality, then 2 protons will be bound when the BNC is reduced by 2
      electrons in the reductive half of the reaction cycle. The effective pK(a)s of
      ionizable residues around the BNC are evaluated in Rhodobacter sphaeroides
      cytochrome c oxidase. At pH 7, only a hydroxide coordinated to Cu(B) shifts its
      pK(a) from below 7 to above 7 and so picks up a proton when heme a(3) and Cu(B)
      are reduced. Glu I-286, Tyr I-288, His I-334, and a second hydroxide on heme a(3)
      all have pK(a)s above 7 in all redox states, although they have only 1.6-3.5
      DeltapK units energy cost for deprotonation. Thus, at equilibrium, they are
      protonated and cannot serve as proton acceptors. The propionic acids near the BNC
      are deprotonated with pK(a)s well below 7. They are well stabilized in their
      anionic state and do not bind a proton upon BNC reduction. This suggests that
      electroneutrality in the BNC is not maintained during the anaerobic reduction.
      Proton uptake on reduction of Cu(A), heme a, heme a(3), and Cu(B) shows
      approximately 2.5 protons bound per 4 electrons, in agreement with prior
      experiments. One proton is bound by a hydroxyl group in the BNC and the rest to
      groups far from the BNC. The electrochemical midpoint potential (E(m)) of heme a
      is calculated in the fully oxidized protein and with 1 or 2 electrons in the BNC.
      The E(m) of heme a shifts down when the BNC is reduced, which agrees with prior
      experiments. If the BNC reduction is electroneutral, then the heme a E(m) is
      independent of the BNC redox state.

PMID- 16800623
TI  - An alternative clamp loading pathway via the T4 clamp loader gp44/62-DNA complex.
AB  - In bacteriophage T4, a clamp loading pathway that utilizes the T4 clamp loader
      (gp44/62) and ATP hydrolysis initially to form a complex with the clamp (gp45)
      has been demonstrated, followed by interaction with DNA and closing of the clamp.
      However, the recent observation that gp45 exists as an opened form in solution
      raises the possibility of other pathways for clamp loading. In this study, an
      alternative clamp loading sequence is evaluated in which gp44/62 first recognizes
      the DNA substrate and then sequesters the clamp from solution and loads it onto
      DNA. This pathway differs in terms of the initial formation of a gp44/62-DNA
      complex that is capable of loading gp45. In this work, we demonstrate ATP
      dependent DNA binding by gp44/62. Among various DNA structures that were tested,
      gp44/62 binds specifically to primer-template DNA but not to single-stranded DNA
      or blunt-end duplex DNA. By tracing the dynamic clamp closing with pre-steady
      state FRET measurements, we show that the clamp loader-DNA complex is functional
      in clamp loading. Furthermore, pre-steady-state ATP hydrolysis experiments
      suggest that 1 equiv of ATP is hydrolyzed when gp44/62 binds to DNA, and
      additional ATP hydrolysis is associated with the completion of the clamp loading
      process. We also investigated the detailed kinetics of binding of MANT-nucleotide
      to gp44/62 through stopped-flow FRET and demonstrated a conformational change as
      the result of ATP, but not ADP binding. The collective kinetic data allowed us to
      propose and evaluate a sequence of steps describing this alternative pathway for
      clamp loading and holoenzyme formation.

PMID- 16800624
TI  - Single-molecule investigation of the T4 bacteriophage DNA polymerase holoenzyme:
      multiple pathways of holoenzyme formation.
AB  - In T4 bacteriophage, the DNA polymerase holoenzyme is responsible for accurate
      and processive DNA synthesis. The holoenzyme consists of DNA polymerase gp43 and
      clamp protein gp45. To form a productive holoenzyme complex, clamp loader protein
      gp44/62 is required for the loading of gp45, along with MgATP, and also for the
      subsequent binding of polymerase to the loaded clamp. Recently published evidence
      suggests that holoenzyme assembly in the T4 replisome may take place via more
      than one pathway [Zhuang, Z., Berdis, A. J., and Benkovic, S. J. (2006)
      Biochemistry 45, 7976-7989]. To demonstrate unequivocally whether there are
      multiple pathways leading to the formation of a productive holoenzyme, single
      molecule fluorescence microscopy has been used to study the potential clamp
      loading and holoenzyme assembly pathways on a single-molecule DNA substrate. The
      results obtained reveal four pathways that foster the formation of a functional
      holoenzyme on DNA: (1) clamp loader-clamp complex binding to DNA followed by
      polymerase, (2) clamp loader binding to DNA followed by clamp and then
      polymerase, (3) clamp binding to DNA followed by clamp loader and then
      polymerase, and (4) polymerase binding to DNA followed by the clamp loader-clamp
      complex. In all cases, MgATP is required. The possible physiological significance
      of the various assembly pathways is discussed in the context of replication
      initiation and lagging strand synthesis during various stages of T4 phage
      replication.

PMID- 16800625
TI  - Structural insight into poplar glutaredoxin C1 with a bridging iron-sulfur
      cluster at the active site.
AB  - Glutaredoxins are glutathione-dependent enzymes that function to reduce disulfide
      bonds in vivo. Interestingly, a recent discovery indicates that some
      glutaredoxins can also exist in another form, an iron-sulfur protein [Lillig, C.
      H., et al. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 8168-8173]. This provides a
      direct connection between glutaredoxins and iron-sulfur proteins, suggesting a
      possible new regulatory role of iron-sulfur clusters along with the new
      functional switch of glutaredoxins. Biochemical studies have indicated that
      poplar glutaredoxin C1 (Grx-C1) is also such a biform protein. The apo form
      (monomer) of Grx-C1 is a regular glutaredoxin, and the holo form (dimer) is an
      iron-sulfur protein with a bridging [2Fe-2S] cluster. Here, we report the
      structural characterizations of poplar Grx-C1 in both the apo and holo forms by
      NMR spectroscopy. The solution structure of the reduced apo Grx-C1, which is the
      first plant Grx structure, shows a typical Grx fold. When poplar Grx-C1 forms a
      dimer with an iron-sulfur cluster, each subunit of the holo form still retains
      the overall fold of the apo form. The bridging iron-sulfur cluster in holo Grx-C1
      is coordinated near the active site. In addition to the iron-sulfur cluster
      linker, helix alpha3 of each subunit is probably involved in the direct contact
      between the two subunits. Moreover, two glutathione molecules are identified in
      the vicinity of the iron-sulfur cluster and very likely participate in cluster
      coordination. Taken together, we propose that the bridging [2Fe-2S] cluster is
      coordinated by the first cysteine at the glutaredoxin active site from each
      subunit of holo Grx-C1, along with two cysteines from two glutathione molecules.
      Our studies reveal that holo Grx-C1 has a novel structural and iron-sulfur
      cluster coordination pattern for an iron-sulfur protein.

PMID- 16800626
TI  - Endogenously nitrated proteins in mouse brain: links to neurodegenerative
      disease.
AB  - Increased abundance of nitrotyrosine modifications of proteins have been
      documented in multiple pathologies in a variety of tissue types and play a role
      in the redox regulation of normal metabolism. To identify proteins sensitive to
      nitrating conditions in vivo, a comprehensive proteomic data set identifying 7792
      proteins from a whole mouse brain, generated by LC/LC-MS/MS analyses, was used to
      identify nitrated proteins. This analysis resulted in the identification of 31
      unique nitrotyrosine sites within 29 different proteins. More than half of the
      nitrated proteins that have been identified are involved in Parkinson's disease,
      Alzheimer's disease, or other neurodegenerative disorders. Similarly,
      nitrotyrosine immunoblots of whole brain homogenates show that treatment of mice
      with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an experimental model
      of Parkinson's disease, induces an increased level of nitration of the same
      protein bands observed to be nitrated in brains of untreated animals. Comparing
      sequences and available high-resolution structures around nitrated tyrosines with
      those of unmodified sites indicates a preference of nitration in vivo for surface
      accessible tyrosines in loops, a characteristic consistent with peroxynitrite
      induced tyrosine modification. In addition, most sequences contain cysteines or
      methionines proximal to nitrotyrosines, contrary to suggestions that these amino
      acid side chains prevent tyrosine nitration. More striking is the presence of a
      positively charged moiety near the sites of nitration, which is not observed for
      non-nitrated tyrosines. Together, these observations suggest a predictive tool of
      functionally important sites of nitration and that cellular nitrating conditions
      play a role in neurodegenerative changes in the brain.

PMID- 16800627
TI  - Insulin signaling in vascular endothelial cells: a key role for heterotrimeric G
      proteins revealed by siRNA-mediated Gbeta1 knockdown.
AB  - Activation of insulin receptors stimulates the phosphoinositide 3-kinase (PI3
      K)/Akt signaling pathway in vascular endothelial cells. Heterotrimeric G proteins
      appear to modulate some of the cellular responses that are initiated by receptor
      tyrosine kinases, but the roles of specific G protein subunits in signaling are
      less clearly defined. We found that insulin treatment of cultured bovine aortic
      endothelial cells (BAEC) activates the alpha isoform of PI3-K (PI3-Kalpha) and
      discovered that purified G protein Gbeta1gamma2 inhibits PI3-Kalpha enzyme
      activity. Transfection of BAEC with a duplex siRNA targeting bovine Gbeta1 leads
      to a 90% knockdown in Gbeta1 protein levels, with no effect on expression of
      other G protein subunits. siRNA-mediated Gbeta1 knockdown markedly and
      specifically potentiates insulin-dependent activation of kinase Akt, likely
      reflecting the removal of the inhibitory effect of Gbetagamma on PI3-Kalpha
      activity. Insulin-induced tyrosine phosphorylation of insulin receptors is
      unaffected by Gbeta1 siRNA. By contrast, Gbeta1 knockdown leads to a significant
      decrease in the level of serine phosphorylation of the insulin receptor substrate
      IRS-1. We explored the effects of siRNA on several serine/threonine protein
      kinases that have been implicated in insulin signaling. Gbeta1 siRNA
      significantly attenuates phosphorylation of the 70 kDa ribosomal protein S6
      kinase (p70S6K) in the basal state and following insulin treatment. We also found
      that IGF-1-initiated activation of Akt is significantly enhanced after siRNA
      mediated Gbeta1 knockdown, while IGF-1-induced p70S6K activation is markedly
      suppressed following transfection of Gbeta1 siRNA. We propose that Gbeta1
      participates in the activation of p70S6K, which in turn promotes the serine
      phosphorylation and inhibition of IRS-1. Taken together, these studies suggest
      that Gbeta1 plays an important role in insulin and IGF-1 signaling in endothelial
      cells, both by inhibiting the activity of PI3-Kalpha and by stimulating pathways
      that lead to activation of protein kinase p70S6K and to the serine
      phosphorylation of IRS-1.

PMID- 16800628
TI  - Stimulation of P-glycoprotein ATPase by analogues of tetramethylrosamine:
      coupling of drug binding at the "R" site to the ATP hydrolysis transition state.
AB  - The multidrug resistance efflux pump P-glycoprotein (Pgp) couples drug export to
      ATP binding and hydrolysis. Details regarding drug trajectory, as well as the
      molecular basis for coupling, remain unknown. Nearly all drugs exported by Pgp
      have been assayed for competitive behavior with rhodamine123 transport at a
      canonical "R" drug binding site. Tetramethylrosamine (TMR) displays a relatively
      high affinity for Pgp when compared to other rhodamines. Here, we present the
      construction and characterization of a library of compounds based upon the TMR
      scaffold and use this set to assess the determinants of drug binding to the "R"
      site of Pgp. This set contained modifications in (1) the number, location, and
      conformational mobility of hydrogen-bond acceptors; (2) the heteroatom in the
      xanthylium core; and (3) the size of the substituent in the 9-position of the
      xanthylium core. Relative specificity for coupling to the distal ATP catalytic
      site was assessed by ATPase stimulation. We found marked ( approximately 1000
      fold) variation in the ATPase specificity constant within the library of TMR
      analogues. Using established methods involving ADP-Vi trapping by wild-type Pgp
      and ATP binding by catalytic carboxylate mutant Pgp, these effects can be
      extended to ATP hydrolysis transition-state stabilization and ATP occlusion at a
      single site. These data support the idea that drugs trigger the engagement of ATP
      catalytic site residues necessary for hydrolysis. Further, the nature of the drug
      binding site and coupling mechanism may be dissected by variation of a drug-like
      scaffold. These studies may facilitate development of novel competitive
      inhibitors at the "R" drug site.

PMID- 16800629
TI  - RNA-Binding affinities and crystal structure of oligonucleotides containing five
      atom amide-based backbone structures.
AB  - Among the hundreds of nucleic acid analogues that have been studied over the last
      two decades only very few exhibit backbones with linkers between residues that
      are either shorter or longer than the four-atom linker O3'-P-O5'-C5' connecting
      sugar ring moieties in DNA and RNA. 2'-Deoxyribonucleoside dimers connected by a
      five-atom linker O3'-CH(CH(3))-CO-NH-CH(2) (*designates a chiral center) were
      reported to lead to only a slight destabilization of RNA-DNA hybrids in which the
      DNA strand contained one or several of these amide-linked dimers (De Napoli, L.,
      Iadonisi, A., Montesarchio, D., Varra, M., and Piccialli, G. (1995) Synthesis of
      thymidine dimers containing a new internucleosidic amide linkage and their
      incorporation into oligodeoxyribonucleotides, Bioorg. Med. Chem. Lett. 5, 1647
      1652). To analyze the influence of various chemistries of such five-atom amide
      linkers on the RNA-binding affinity of modified DNA strands, we have synthesized
      five different amide-linked dimers, including structures with homochiral linkers
      of the type X3'-C*H(CH(3))-CO-NH-CH(2) (X = O, CH(2)) as well as the
      corresponding analogues carrying methoxy groups at the 2'-position of the 3'
      nucleosides. We have conducted a detailed thermodynamic analysis of duplex
      formation between the modified DNA and RNA, with the DNA strands containing
      between one and seven consecutive modified dimers. Some of the five-atom-linked
      dimers lead to significantly higher RNA-binding affinities compared with that of
      native DNA. Interestingly, the linkers with opposite stereochemistry at the
      chiral center stabilize duplexes between the modified DNA and RNA to different
      degrees. CD spectroscopy in solution and a crystal structure of an RNA-DNA duplex
      with a single amide-linked dimer demonstrate that the longer amide backbones do
      not disrupt the duplex geometry. These observations provide further evidence that
      stable cross-pairing between two different types of nucleic acids does not
      require the numbers of atoms linking their individual residues to match.

PMID- 16800630
TI  - Structural determinants of HscA peptide-binding specificity.
AB  - The Hsp70-class molecular chaperone HscA interacts specifically with a conserved
      (99)LPPVK(103) motif of the iron-sulfur cluster scaffold protein IscU. We used a
      cellulose-bound peptide array to perform single-site saturation substitution of
      peptide residues corresponding to Glu(98)-Ile(104) of IscU to determine
      positional amino acid requirements for recognition by HscA. Two mutant chaperone
      forms, HscA(F426A) with a DnaK-like arch structure and HscA(M433V) with a DnaK
      like substrate-binding pocket, were also studied. Wild-type HscA and HscA(F426A)
      exhibited a strict preference for proline in the central peptide position
      (ELPPVKI), whereas HscA(M433V) bound a peptide containing a Pro-->Leu
      substitution at this location (ELPLVKI). Contributions of Phe(426) and Met(433)
      to HscA peptide specificity were further tested in solution using a fluorescence
      based peptide-binding assay. Bimane-labeled HscA and HscA(F426A) bound ELPPVKI
      peptides with higher affinity than leucine-substituted peptides, whereas
      HscA(M433V) favored binding of ELPLVKI peptides. Fluorescence-binding studies
      were also carried out with derivatives of the peptide NRLLLTG, a model substrate
      for DnaK. HscA and HscA(F426A) bound NRLLLTG peptides weakly, whereas HscA(M433V)
      bound NRLLLTG peptides with higher affinity than IscU-derived peptides ELPPVKI
      and ELPLVKI. These results suggest that the specificity of HscA for the LPPVK
      recognition sequence is determined in part by steric obstruction of the
      hydrophobic binding pocket by Met(433) and that substitution with the Val(433)
      sidechain imparts a broader, more DnaK-like, substrate recognition pattern.

PMID- 16800631
TI  - Probing the secondary structure of expansion segment ES6 in 18S ribosomal RNA.
AB  - Expansion segment ES6 in 18S ribosomal RNA is, unlike many other expansion
      segments, present in all eukaryotes. The available data suggest that ES6 is
      located on the surface of the small ribosomal subunit. Here we have analyzed the
      secondary structure of the complete ES6 sequence in intact ribosomes from three
      eukaryotes, wheat, yeast, and mouse, representing different eukaryotic kingdoms.
      The availability of the ES6 sequence for modification and cleavage by structure
      sensitive chemicals and enzymatic reagents was analyzed by primer extension and
      gel electrophoresis on an ABI 377 automated DNA sequencer. The experimental
      results were used to restrict the number of possible secondary structure models
      of ES6 generated by the folding software MFOLD. The modification data obtained
      from the three experimental organisms were very similar despite the sequence
      variation. Consequently, similar secondary structure models were obtained for the
      ES6 sequence in wheat, yeast, and mouse ribosomes. A comparison of sequence data
      from more than 6000 eukaryotes showed that similar structural elements could also
      be formed in other organisms. The comparative analysis also showed that the
      extent of compensatory base changes in the suggested helices was low. The in situ
      structure analysis was complemented by a secondary structure analysis of wheat
      ES6 transcribed and folded in vitro. The obtained modification data indicate that
      the secondary structure of the in vitro transcribed sequence differs from that
      observed in the intact ribosome. These results suggest that chaperones, ribosomal
      proteins, and/or tertiary rRNA interactions could be involved in the in vivo
      folding of ES6.

PMID- 16800633
TI  - Asymmetric stability among the transmembrane helices of lactose permease.
AB  - Combining structure determinations from nuclear magnetic resonance (NMR) data and
      molecular dynamics simulations (MD) under the same environmental conditions
      revealed a startling asymmetry in the intrinsic conformational stability of
      secondary structure in the transmembrane domain of lactose permease (LacY).
      Eleven fragments, corresponding to transmembrane segments (TMs) of LacY, were
      synthesized, and their secondary structure in solution was determined by NMR.
      Eight of the TMs contained significant regions of helical structure. MD
      simulations, both in DMSO and in a DMPC bilayer, showed sites of local stability
      of helical structure in these TMs, punctuated by regions of conformational
      instability, in substantial agreement with the NMR data. Mapping the stable
      regions onto the crystal structure of LacY reveals a marked asymmetry,
      contrasting with the pseudosymmetry in the static structure: the secondary
      structure in the C-terminal half is more stable than in the N-terminal half. The
      relative stability of secondary structure is likely exploited in the transport
      mechanism of LacY. Residues supporting proton conduction are in more stable
      regions of secondary structure, while residues key to substrate binding are found
      in considerably unstable regions of secondary structure.

PMID- 16800632
TI  - The nondiscriminating aspartyl-tRNA synthetase from Helicobacter pylori:
      anticodon-binding domain mutations that impact tRNA specificity and heterologous
      toxicity.
AB  - Divergent tRNA substrate recognition patterns distinguish the two distinct forms
      of aspartyl-tRNA synthetase (AspRS) that exist in different bacteria. In some
      cases, a canonical, discriminating AspRS (D-AspRS) specifically generates Asp
      tRNA(Asp) and usually coexists with asparaginyl-tRNA synthetase (AsnRS). In other
      bacteria, particularly those that lack AsnRS, AspRS is nondiscriminating (ND
      AspRS) and generates both Asp-tRNA(Asp) and the noncanonical, misacylated Asp
      tRNA(Asn); this misacylated tRNA is subsequently repaired by the glutamine
      dependent Asp-tRNA(Asn)/Glu-tRNA(Gln) amidotransferase (Asp/Glu-Adt). The
      molecular features that distinguish the closely related bacterial D-AspRS and ND
      AspRS are not well-understood. Here, we report the first characterization of the
      ND-AspRS from the human pathogen Helicobacter pylori (H. pylori or Hp). This
      enzyme is toxic when heterologously overexpressed in Escherichia coli. This
      toxicity is rescued upon coexpression of the Hp Asp/Glu-Adt, indicating that Hp
      Asp/Glu-Adt can utilize E. coli Asp-tRNA(Asn) as a substrate. Finally, mutations
      in the anticodon-binding domain of Hp ND-AspRS reduce this enzyme's ability to
      misacylate tRNA(Asn), in a manner that correlates with the toxicity of the enzyme
      in E. coli.

PMID- 16800634
TI  - Ultrastructure of human erythrocyte GLUT1.
AB  - This study was undertaken to examine GLUT1 quaternary structure. Independent but
      complementary methodologies were used to investigate the influence of membrane
      solubilizing detergents on GLUT1/lipid/detergent micelle hydrodynamic radii.
      Hydrodynamic size analysis and electron microscopy of GLUT1/lipid/detergent
      micelles and freeze-fracture electron microscopy of GLUT1 proteoliposomes support
      the hypothesis that the glucose transporter is a multimeric (probably tetrameric)
      complex of GLUT1 proteins. GLUT1 forms a multimeric complex in octyl glucoside
      that dissociates upon addition of reductant. Some detergents (e.g., CHAPS and
      dodecyl maltoside) promote the dissociation of GLUT1 oligomers into smaller
      aggregation states (dimers or monomers). These complexes do not reassemble as
      larger oligomers when dissociating detergents are subsequently replaced with
      nondissociating detergents such as octyl glucoside or cholic acid. When
      dissociating detergents are replaced with lipids, the resulting proteoliposomes
      catalyze protein-mediated sugar transport, and the subsequent addition of
      solubilizing, nondissociating detergents generates higher (tetrameric) GLUT1
      aggregation states. These findings suggest that some detergents stabilize while
      others destabilize GLUT1 quaternary structure. GLUT1 does not appear to exchange
      rapidly between protein/lipid/detergent micelles but is able to self-associate in
      the plane of the lipid bilayer.

PMID- 16800635
TI  - Carboxyl terminus of Helicobacter pylori alpha1,3-fucosyltransferase determines
      the structure and stability.
AB  - Helicobacter pylori is well known as the primary cause of gastritis, duodenal
      ulcers, and gastric cancer. The pathogenic bacteria produces Lewis x and Lewis y
      epitopes in the O-antigens of lipopolysaccharides to mimic the carbohydrate
      antigens of gastric epithelial cells to avoid detection by the host's immune
      system. The enzyme alpha1,3-fucosyltransferase from H. pylori catalyzes the
      glycosyl addition of fucose from the donor GDP-fucose to the acceptor N
      acetyllactosamine. The poor solubility of the enzyme was resolved by systematic
      deletion of the C-terminus. We report here the first structural analysis using CD
      spectroscopy and analytical ultracentrifugation. The results indicate that up to
      80 residues, including the tail rich in hydrophobic and positively charged
      residues (sequence 434-478) and 5 of the 10 tandem repeats of 7 amino acids each
      (399-433), can be removed without significant change in structure and catalysis.
      Half of the heptad repeats are required to maintain both the secondary and native
      quaternary structures. Removal of more residues in the C-terminus led to major
      structural alteration, which was correlated with the loss of enzymatic activity.
      In accordance with the thermal denaturation studies, the results support the idea
      that a higher number of tandem repeats functioning to facilitate a dimeric
      structure helps to prevent the protein from unfolding during incubation at higher
      temperatures.

PMID- 16800636
TI  - Synergistic pore formation by type III toxin translocators of Pseudomonas
      aeruginosa.
AB  - Type III secretion/translocation systems are essential actors in the
      pathogenicity of Gram-negative bacteria. The injection of bacterial toxins across
      the host cell plasma membranes is presumably accomplished by a proteinaceous
      structure, the translocon. In vitro, Pseudomonas aeruginosa translocators PopB
      and PopD form ringlike structures observed by electron microscopy. We demonstrate
      here that PopB and PopD are functionally active and sufficient to form pores in
      lipid vesicles. Furthermore, the two translocators act in synergy to promote
      membrane permeabilization. The size-based selectivity observed for the passage of
      solutes indicates that the membrane permeabilization is due to the formation of
      size-defined pores. Our results provide also new insights into the mechanism of
      translocon pore formation that may occur during the passage of toxins from the
      bacterium into the cell. While proteins bind to lipid vesicles equally at any pH,
      the kinetics of membrane permeabilization accelerate progressively with
      decreasing pH values. Electrostatic interactions and the presence of anionic
      lipids were found to be crucial for pore formation whereas cholesterol did not
      appear to play a significant role in functional translocon formation.

PMID- 16800637
TI  - Topography of the hydrophilic helices of membrane-inserted diphtheria toxin T
      domain: TH1-TH3 as a hydrophilic tether.
AB  - After low pH-triggered membrane insertion, the T domain of diphtheria toxin helps
      translocate the catalytic domain of the toxin across membranes. In this study,
      the hydrophilic N-terminal helices of the T domain (TH1-TH3) were studied. The
      conformation triggered by exposure to low pH and changes in topography upon
      membrane insertion were studied. These experiments involved bimane or BODIPY
      labeling of single Cys introduced at various positions, followed by the
      measurement of bimane emission wavelength, bimane exposure to fluorescence
      quenchers, and antibody binding to BODIPY groups. Upon exposure of the T domain
      in solution to low pH, it was found that the hydrophobic face of TH1, which is
      buried in the native state at neutral pH, became exposed to solution. When the T
      domain was added externally to lipid vesicles at low pH, the hydrophobic face of
      TH1 became buried within the lipid bilayer. Helices TH2 and TH3 also inserted
      into the bilayer after exposure to low pH. However, in contrast to helices TH5
      TH9, overall TH1-TH3 insertion was shallow and there was no significant change in
      TH1-TH3 insertion depth when the T domain switched from the shallowly inserting
      (P) to deeply inserting (TM) conformation. Binding of streptavidin to
      biotinylated Cys residues was used to investigate whether solution-exposed
      residues of membrane-inserted T domain were exposed on the external or internal
      surface of the bilayer. These experiments showed that when the T domain is
      externally added to vesicles, the entire TH1-TH3 segment remains on the cis
      (outer) side of the bilayer. The results of this study suggest that membrane
      inserted TH1-TH3 form autonomous segments that neither deeply penetrate the
      bilayer nor interact tightly with the translocation-promoting structure formed by
      the hydrophobic TH5-TH9 subdomain. Instead, TH1-TH3 may aid translocation by
      acting as an A-chain-attached flexible tether.

PMID- 16800638
TI  - Alpha-synuclein can function as an antioxidant preventing oxidation of
      unsaturated lipid in vesicles.
AB  - Alpha-synuclein, a presynaptic protein associated with Parkinson's disease, is
      found as both soluble cytosolic and membrane-bound forms. Although the function
      of alpha-synuclein is unknown, several observations suggest that its association
      with membranes is important. In the present study we investigated the effect of
      alpha-synuclein on lipid oxidation in membranes containing phospholipids with
      unsaturated fatty acids. The kinetics of lipid oxidation were monitored by the
      change in fluorescence intensity of the dye C11-BODIPY. We find that monomeric
      alpha-synuclein efficiently prevented lipid oxidation, whereas fibrillar alpha
      synuclein had no such effect. Our data suggest that the prevention of unsaturated
      lipid oxidation by alpha-synuclein requires that it bind to the lipid membrane.
      The antioxidant function of alpha-synuclein is attributed to its facile oxidation
      via the formation of methionine sulfoxide, as shown by mass spectrometry. These
      findings suggest that the inhibition of lipid oxidation by alpha-synuclein may be
      a physiological function of the protein.

PMID- 16800639
TI  - New insights into the self-assembly of insulin amyloid fibrils: an H-D exchange
      FT-IR study.
AB  - The solvent protection of the amide backbone in bovine insulin fibrils was
      studied by FT-IR spectroscopy. In the mature fibrils, approximately 85 +/- 2% of
      amide protons are protected. Of those "trapped" protons, a further 25 +/- 2 or 35
      +/- 2% is H-D exchanged after incubation for 1 h at 1 GPa and 25 degrees C or 0.1
      MPa and 100 degrees C, respectively. In contrast to the native or unfolded
      protein, fibrils do not H-D exchange upon incubation at 65 degrees C. A complete
      deuteration of H(2)O-grown fibrils occurs when the beta-sheet structure is
      reassembled in a 75 wt % DMSO/D(2)O solution. Our findings suggest a densely
      packed environment around the amide protons involved in the intermolecular beta
      sheet motive. In disagreement with the concept of "amyloid fibers as water-filled
      nanotubes" [Perutz, M. F., et al. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 5591
      5595], elution of D(2)O-grown fibrils with H(2)O is complete, which is reflected
      by the vanishing of D(2)O bending vibrations at 1214 cm(-)(1). This implies the
      absence of "trapped water" within insulin fibrils. The rigid conformations of the
      native and fibrillar insulin contrast with transient intermediate states docking
      at the fibrils' ends. Room-temperature seeding is accompanied by an accelerated H
      D exchange in insulin molecules in the act of docking and integrating with the
      seeds, proving that the profound structural disruption is the sine qua non of
      forming an aggregation-competent conformation.

PMID- 16800640
TI  - Evidence for rapid inter- and intramolecular chlorine transfer reactions of
      histamine and carnosine chloramines: implications for the prevention of
      hypochlorous-acid-mediated damage.
AB  - Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and Cl(-)
      by the heme enzyme myeloperoxidase, which is released from activated leukocytes.
      HOCl possesses potent antibacterial properties, but excessive production can lead
      to host tissue damage that is implicated in a wide range of human diseases (e.g.,
      atherosclerosis). Histamine and carnosine have been proposed as protective agents
      against such damage. However, as recent studies have shown that histidine
      containing compounds readily form imidazole chloramines that can rapidly
      chlorinate other targets, it was hypothesized that similar reactions may occur
      with histamine and carnosine, leading to propagation, rather than prevention, of
      HOCl-mediated damage. In this study, the reactions of HOCl with histamine,
      histidine, carnosine, and other compounds containing imidazole and free amine
      sites were examined. In all cases, rapid formation (k, 1.6 x 10(5) M(-)(1) s(
      )(1)) of imidazole chloramines was observed, followed by chlorine transfer to
      yield more stable, primary chloramines (R-NHCl). The rates of most of these
      secondary reactions are dependent upon substrate concentrations, consistent with
      intermolecular mechanisms (k, 10(3)-10(4) M(-)(1) s(-)(1)). However, for
      carnosine, the imidazole chloramine transfer rates are independent of the
      concentration, indicative of intramolecular processes (k, 0.6 s(-)(1)). High
      performance liquid chromatography studies show that in all cases the resultant R
      NHCl species can slowly chlorinate N-alpha-acetyl-Tyr. Thus, the current data
      indicate that the chloramines formed on the imidazole and free amine groups of
      these compounds can oxidize other target molecules but with limited efficiency,
      suggesting that histamine and particularly carnosine may be able to limit HOCl
      mediated oxidation in vivo.

PMID- 16800641
TI  - Vi antigen biosynthesis in Salmonella typhi: characterization of UDP-N
      acetylglucosamine C-6 dehydrogenase (TviB) and UDP-N-acetylglucosaminuronic acid
      C-4 epimerase (TviC).
AB  - Vi antigen, the virulence factor of Salmonella typhi, has been used clinically as
      a molecular vaccine. TviB and TviC are two enzymes involved in the formation of
      Vi antigen, a linear polymer consisting of alpha-1,4-linked N
      acetylgalactosaminuronate. Protein sequence analysis suggests that TviB is a
      dehydrogenase and TviC is an epimerase. Both enzymes are expected to be NAD(+)
      dependent. In order to verify their functions, TviB and TviC were cloned,
      expressed in Escherichia coli, and characterized. The C-terminal His(6)-tagged
      TviB protein, purified from soluble cell fractions in the presence of 10 mM DTT,
      shows UDP-N-acetylglucosamine 6-dehydrogenase activity and is capable of
      catalyzing the conversion of UDP-N-acetylglucosamine (UDP-GlcNAc) to UDP-N
      acetylglucosaminuronic acid (UDP-GlcNAcA) with a k(cat) value of 15.5 +/- 1.0
      min(-)(1). The K(m) values of TviB for UDP-GlcNAc and NAD(+) are 77 +/- 9 microM
      and 276 +/- 52 microM, respectively. TviC, purified as C-terminal hexahistidine
      tagged protein, shows UDP-GlcNAcA 4-epimerase and UDP-N-acetylgalactosamine (UDP
      GalNAc) 4-epimerase activities. The K(m) values of TviC for UDP-GlcNAcA and UDP-N
      acetylgalactosaminuronic acid (UDP-GalNAcA) are 20 +/- 1 microM and 42 +/- 2
      microM, respectively. The k(cat) value for the conversion of UDP-GlcNAcA to UDP
      GalNAcA is 56.8 +/- 0.5 min(-)(1), while that for the reverse reaction is 39.1 +/
      0.6 min(-)(1). These results show that the biosynthesis of Vi antigen is
      initiated by the TviB-catalyzed oxidation of UDP-GlcNAc to UDP-GalNAc, followed
      by the TviC-catalyzed epimerization at C-4 to form UDP-GalNAcA, which serves as
      the building block for the formation of Vi polymer. These results set the stage
      for future in vitro biosynthesis of Vi antigen. These enzymes may also be drug
      targets to inhibit Vi antigen production.

PMID- 16800642
TI  - Time study of DNA condensate morphology: implications regarding the nucleation,
      growth, and equilibrium populations of toroids and rods.
AB  - It is well known that multivalent cations cause free DNA in solution to condense
      into nanometer-scale particles with toroidal and rod-like morphologies. However,
      it has not been shown to what degree kinetic factors (e.g., condensate
      nucleation) versus thermodynamic factors (e.g., DNA bending energy) determine
      experimentally observed relative populations of toroids and rods. It is also not
      clear how multimolecular DNA toroids and rods interconvert in solution. We have
      conducted a series of condensation studies in which DNA condensate morphology
      statistics were measured as a function of time and DNA structure. Here, we show
      that in a typical in vitro DNA condensation reaction, the relative rod population
      2 min after the initiation of condensation is substantially greater than that
      measured after morphological equilibrium is reached (ca. 20 min). This higher
      population of rods at earlier time points is consistent with theoretical studies
      that have suggested a favorable kinetic pathway for rod nucleation. By using
      static DNA loops to alter the kinetics and thermodynamics of condensation, we
      further demonstrate that reported increases in rod populations associated with
      decreasing DNA length are primarily due to a change in the thermodynamics of DNA
      condensation, rather than a change in the kinetics of condensate nucleation or
      growth. The results presented also reveal that the redistribution of DNA from
      rods to toroids is mediated through the exchange of DNA strands with solution.

PMID- 16800644
TI  - Nanoscale surface patterns from 10(3) single molecule helices of biodegradable
      poly(L-lactic acid).
AB  - Atomic force microscopy, reflection absorption infrared spectroscopy, and X-ray
      reflectivity studies reveal that poly(L-lactic acid) molecules in Langmuir
      Blodgett (LB) films exist as 10(3) helices over nearly the entire length of the
      polymer chain. This feature gives rise to LB films with highly ordered nanoscale
      smectic liquid crystalline-like surface patterns with low surface roughness and
      lamellar spacings that scale with molar mass. These studies provide a new
      approach for controlling surface morphology with a biodegradable polymer commonly
      used for drug delivery and tissue engineering.

PMID- 16800643
TI  - Oxygen- and glucose-dependent expression of Trhxt1, a putative glucose
      transporter gene of Trichoderma reesei.
AB  - The filamentous fungus Trichoderma reesei is adapted to nutrient-poor
      environments, in which it uses extracellular cellulases to obtain glucose from
      the available cellulose biomass. We have isolated and characterized Trhxt1, a
      putative glucose transporter gene, as judged by the glucose accumulation
      phenotype of a DeltaTrhxt1 mutant. This gene is repressed at high glucose
      concentrations and expressed at micromolar levels and in the absence of glucose.
      The gene is also induced during the growth of T. reesei on cellulose when the
      glucose concentration generated from the hydrolysis of cellulose present in the
      culture medium is in the micromolar range. We also show that oxygen availability
      controls the expression of the Trxht1 gene. In this regard, the gene is down
      regulated by hypoxia and also by the inhibition of the flow of electrons through
      the respiratory chain using antimycin A. Intriguingly, anoxia but not hypoxia
      strongly induces the expression of the gene in the presence of an otherwise
      repressive concentration of glucose. These results indicate that although the
      absence of repressing concentrations of glucose and an active respiratory chain
      are required for Trhxt1 expression under normoxic conditions these physiological
      processes have no effect on the expression of this gene under an anoxic state.
      Thus, our results highlight the presence of a novel coordinated interaction
      between oxygen and the regulatory circuit for glucose repression under anoxic
      conditions.

PMID- 16800645
TI  - Magnetic-sensitive behavior of intelligent ferrogels for controlled release of
      drug.
AB  - An intelligent magnetic hydrogel (ferrogel) was fabricated by mixing poly(vinyl
      alcohol) (PVA) hydrogels and Fe3O4 magnetic particles through freezing-thawing
      cycles. Although the external direct current magnetic field was applied to the
      ferrogel, the drug was accumulated around the ferrogel, but the accumulated drug
      was spurt to the environment instantly when the magnetic fields instantly
      switched "off". Furthermore, rapid to slow drug release can be tunable while the
      magnetic field was switched from "off" to "on" mode. The drug release behavior
      from the ferrogel is strongly dominated by the particle size of Fe3O4 under a
      given magnetic field. The best "magnetic-sensitive effects" are observed for the
      ferrogels with larger Fe3O4 particles due to its stronger saturation
      magnetization and smaller coercive force. Furthermore, the amount of drug release
      can be controlled by fine-tuning of the switching duration time (SDT) through an
      externally controllable on-off operation in a given magnetic field. It was
      demonstrated that the highest burst drug amounts and best "close" configuration
      of the ferrogel were observed for the SDT of 10 and 5 min, respectively. By
      taking these peculiar magnetic-sensitive characteristics of the novel ferrogels
      currently synthesized, it is highly expected to have a controllable or
      programmable drug release profile that can be designed for practical clinical
      needs.

PMID- 16800646
TI  - The load supported by small floating objects.
AB  - We consider the equilibrium flotation of a two-dimensional cylinder and a sphere
      at an interface between two fluids. We give conditions on the density and radius
      of these objects for them to be able to float at the interface and discuss the
      role played by the contact angle in determining these conditions. For cylinders
      with a small radius, we find that the maximum density is independent of contact
      angle but that, for spheres, the contact angle enters at leading order in the
      particle radius. Our theoretical predictions are in agreement with experimental
      results.

PMID- 16800647
TI  - Lamellar to inverted hexagonal mesophase transition in DNA complexes with
      calamitic, discotic, and cubic shaped cationic lipids.
AB  - In this study, we report on the lipid tail molecular shape/size effect on the
      mesophase self-assembly behaviors of various cationic lipids complexed with
      double-stranded DNA. The molecular shape of the cationic lipids was tailored from
      rodlike (a cyanobiphenyl imidazolium salt) to discotic (a triphenylene
      imidazolium salt), and finally to cubic [a polyhedral oligomeric silsesquioxane
      (POSS) imidazolium salt]. An increase in the cross-sectional area of the
      hydrophobic tails with respect to the hydrophilic imidazolium head induced a
      negative spontaneous curvature of the cationic lipids. As a result, a
      morphological change from lamello-columnar (L(C)(alpha)) phase for the DNA
      cyanobiphenyl imidazolium salt (DNA-rod) and DNA-triphenylene imidazolium salt
      (DNA-disk) complexes to an inverted hexagonal columnar (H(C)(II)) phase for the
      DNA-POSS imidazolium salt (DNA-cube) complex was observed. The DNA-rod complex
      had a typical smectic A (SmA) L(C)(alpha) morphology, whereas the DNA-disk
      complex had a double lamello-columnar liquid crystalline phase. However, when the
      lipid tail changed to POSS, an H(C)(II) morphology was achieved. These
      morphological changes were successfully characterized by X-ray diffraction and
      transmission electron microscopy. We expect that these liquid crystalline and
      crystalline DNA hybrid materials may become potential functional materials for
      various applications such as organic microelectronics and gene transfection.

PMID- 16800648
TI  - Microstructure, morphology, and lifetime of armored bubbles exposed to
      surfactants.
AB  - We report the behavior of particle-stabilized bubbles (armored bubbles) when
      exposed to various classes and concentrations of surfactants. The bubbles are
      nonspherical, which is a signature of the jamming of the particles on the
      interface, and are stable to dissolution prior to the addition of surfactant.
      Armored bubbles exposed to surfactants, dissolve, and exhibit distinct
      morphological, microstructural, and lifetime changes, which correlate with the
      concentration of surfactant employed. For low concentrations of surfactant, an
      armored bubble remains nonspherical while dissolving, whereas for concentrations
      close to and above the surfactant cmc a bubble reverts to a spherical shape
      before dissolving. We propose a microstructural interpretation, supported by our
      experimental observations of particle dynamics on the bubble interface, that
      recognizes the role of interfacial jamming and stresses in particle-stabilization
      and surfactant-mediated destabilization of armored bubbles.

PMID- 16800649
TI  - New method to determine the viscoelastic properties of admicelles around the
      stick-slip transition.
AB  - We report on a new method by which, for the first time, the viscoelastic
      properties of an adsorbed surfactant layer on a solid surface are measured. It is
      based on an analysis of the amplitude and the phase angle of the pressure
      fluctuations induced by a pulsating flow of a Newtonian surfactant solution
      through cylindrical pores. This method is subsequently used to determine the
      viscoelastic properties of an admicelle, formed when flushing surfactant
      solutions through nanopores, around the stick-slip transition. We find that the
      admicelle responds elastically for flow strengths below the transition and beyond
      the viscous. This is in agreement with the hypothesis formulated earlier (Cheikh,
      C.; Koper, G. J. M. Phys. Rev. Lett. 2003, 91, 156102).

PMID- 16800650
TI  - Controlling the morphology of aggregates of an amphiphilic synthetic receptor
      through host-guest interactions.
AB  - A new amphiphilic receptor containing a macrocyclic anionic headgroup and a
      single alkyl chain was prepared through an efficient templated synthesis. The
      interdependence of the aggregation behavior and the host-guest chemistry was
      studied. In the absence of any guest the terminus of the alkyl chain of the
      receptor is included inside the hydrophobic cavity of the macrocycle (as evident
      from 1H NMR studies) leading to self-assembly into micrometer-long nanotubes (as
      evident from TEM studies). The alkyl chain can be displaced by an acridizinium
      bromide guest (as evident from 1H NMR and ITC), which leads to a dramatic change
      in aggregate size and morphology (as evident from DLS). Studies of the
      solubilization of Nile red suggest that the resulting aggregates are micelles
      with a cmc of around 35 microM. These results represent a new addition to the
      still small number of water-soluble amphiphilic receptors and one of the first
      examples in which specific host-guest chemistry controls the size and shape of
      nanoscale aggregates.

PMID- 16800651
TI  - "Artificial lotus leaf" prepared using a 1945 patent and a commercial textile.
AB  - Two polyester textiles, conventional polyester and microfiber polyester fabrics,
      were hydrophobized using a simple, patented water-repellent silicone coating
      procedure. Water contact angles on these two surfaces are theta(A)/theta(R) = 151
      degrees/140 degrees and theta(A)/theta(R) = 170 degrees/165 degrees,
      respectively. A smooth surface of this of this coating exhibits theta(A)/theta(R)
      = 110 degrees/100 degrees. The binary length scale topography (approximately 2
      microm/ approximately 50 microm) of the microfiber polyester is responsible for
      relieving receding contact line pinning and promoting water repellency that is
      superior to that of the lotus leaf. The recent literature on superhydrophobic
      surfaces is criticized for neglecting literature of the 1940s.

PMID- 16800652
TI  - Micelles in mixtures of sodium dodecyl sulfate and a bolaform surfactant.
AB  - Mixtures composed of water, sodium dodecyl sulfate (SDS), and a bolaform
      surfactant with two aza-crown ethers as polar headgroups (termed Bola C-16) were
      investigated by modulating the mole ratios between the components. The two
      surfactants have ionic and nonionic, but ionizable, headgroups, respectively. The
      ionization is due to the complexation of alkali ions by the aza-crown ether
      unit(s). Structural, thermodynamic, and transport properties of the above
      mixtures were investigated. Results from surface tension, translational self
      diffusion, and small angle neutron scattering (SANS) are reported and discussed.
      Interactions between the two surfactants to form mixed micelles result in a
      combination of electrostatic and hydrophobic contributions. These effects are
      reflected in the size and shape of the aggregates as well as in transport
      properties. The translational diffusion of the components in mixed micelles, in
      particular, depends on the Bola C-16/SDS mole ratio. Nonideality of mixing of the
      two components was inferred from the dependence of the critical micelle
      concentration, cmc, on the mole fraction of Bola C-16. This behavior is also
      reflected in surface adsorption and in the area per polar headgroup at the air
      water interface. SANS data analysis for the pure components gives results in good
      agreement with previous findings. An analysis of data relative to mixed systems
      allows us to compute some structural parameters of the mixed aggregates. The
      dependence of aggregation numbers, nu(T), on the Bola C-16/SDS mole ratio
      displays a maximum that depends on the overall surfactant content and is
      rationalized in terms of the nonideality of mixing. Aggregates grow
      perpendicularly to the major rotation axis, as formerly observed in the Bola C-16
      system, and become progressively ellipsoidal in shape.

PMID- 16800653
TI  - Preparation and tribological study of a peptide-containing alkylsiloxane
      monolayer on silicon.
AB  - A peptide-containing alkylsilane self-assembled monolayer on silicon surface has
      been prepared successfully by a simple one-step strategy. The formation and
      structure of the peptide-containing SAMs were characterized by means of contact
      angle measurement, ellipsometry, FT-IR, and AFM morphology observation. It was
      found that the water content in the hydrolysis solution plays a key role in
      determining the quality of the monolayers. The micro-tribological properties of
      various films were evaluated by using AFM, while the macro-tribological study was
      performed on a ball-on-plate tribometer. It was found that the peptide-containing
      monolayers possess excellent friction-reduction and antiwear ability, which was
      attributed to its amide-containing structure. In other words, the interchain
      hydrogen bonds among the molecules enhance the stability of the monolayers
      against rubbing the counterpart ball and thus endow it an outstanding antiwear
      ability.

PMID- 16800654
TI  - Poly(dimethylamino)ethyl methacrylate for use as a surfactant in the miniemulsion
      polymerization of styrene.
AB  - A novel Y-shaped macromonomer based on poly[(dimethylamino)ethyl methacrylate]
      (PDMAEMA) with a narrow molecular weight distribution was synthesized via
      oxyanion-initiated polymerization in which a potassium alcoholate of trimethylol
      propane allyl ether (2K-TMPAE) was used as a difunctional initiator. For the
      miniemulsion polymerization of styrene, this macromonomer acted well both as a
      comonomer carrying a reactive C=C double bond in its central section and as a pH
      responsive polycationic surfactant in media with different pH values. The
      resulting microspheres composed of a hydrophobic polystyrene core and a
      hydrophilic PDMAEMA-protonated corona have shown spherical morphology and are
      quite stable. The nature of the reactive group, the amount of polymeric
      surfactant, and pH values in the aqueous medium have been systematically
      investigated during the miniemulsion polymerization by analyzing the evolution of
      the monomer conversions. The results of FTIR and (1)H NMR spectra demonstrated
      the generation of the functional particles. The analyses of TEM micrographs and
      dynamic light scattering (DLS) confirmed that the latices had a relatively narrow
      particle size distribution. The measurement of the zeta potential gave further
      evidence of the "hairy" particle structure. Because the reactive group is located
      in the central section of the macromonomer, the stabilization mechanism of the
      polymeric surfactant can be ascribed to (1) the absorption of two polycationic
      and hydrophilic tails that have electrostatic and steric stabilization to
      decrease the interface tension and (2) the copolymerization with the styrene
      monomer.

PMID- 16800655
TI  - Buckling and crumpling of drying droplets of colloid-polymer suspensions.
AB  - Spray drying of complex liquids to form solid powders is important in many
      industrial applications. One of the challenges associated with spray drying is
      controlling the morphologies of the powders produced; this requires an
      understanding of how drying mechanics depend on the ingredients and conditions.
      We demonstrate that the morphology of powders produced by spray drying colloidal
      polystyrene (PS) suspensions can be significantly altered by changing the
      molecular weight of dissolved poly(ethylene oxide) (PEO). Samples containing high
      molecular-weight PEO produce powders with more crumpled morphologies than those
      containing low-molecular-weight PEO. Observations of drying droplets suspended by
      a thin film of vapor suggest that this occurs because the samples with high
      molecular-weight PEO buckle earlier in the drying process when the droplets are
      larger. Earlier buckling times are likely caused by the decreased stability,
      demonstrated by bulk rheology experiments, of PS particles in the presence of
      high-molecular-weight PEO at elevated temperatures. We present a consistent
      picture in which decreased particle stability hastens droplet buckling and leads
      to more crumpled powder morphologies; this underscores the importance of
      interparticle forces in determining the buckling of particle-laden droplets.

PMID- 16800656
TI  - New class of aggregates in aqueous solution: an NMR, thermodynamic, and dynamic
      light scattering study.
AB  - We investigated the aggregation properties of two classes of aromatic and
      hydrophobic compounds, namely chloroacetamides and ethyl 3-phenyl-2
      nitropropionates, in moderately concentrated aqueous solution (millimolar range).
      The identification of all species present in solution under specific experimental
      conditions was performed by 1D and 2D NMR, pulsed gradient spin-echo NMR, and
      dynamic light scattering techniques. Some physical-chemical properties
      (viscosity, surface tension, and colligative properties) of the aqueous solutions
      were also determined. Both classes of compounds behave quite similarly: in
      solution, three distinct species, namely a monomeric species, small and mobile
      aggregates, and large and stiff aggregates, are observed. The results give
      insight into a new class of aggregates, held together by pi-pi interactions,
      which show an unusual associative behavior in water.

PMID- 16800657
TI  - Effect of thermal treatment, ionic strength, and pH on the short-term and long
      term coalescence stability of beta-lactoglobulin emulsions.
AB  - We present experimental results about the effects of thermal treatment, ionic
      strength, and pH on the protein adsorption and coalescence stability of freshly
      prepared (2 h after emulsification) and 6-day-stored emulsions, stabilized by the
      globular protein beta-lactoglobulin (BLG). In all emulsions studied, the volume
      fraction of the dispersed soybean oil is 30% and the mean drop diameter is d(32)
      approximately 40 microm. The protein concentration, C(BLG), is varied between
      0.02 and 0.1 wt %, the electrolyte concentration, C(EL), between 1.5 mM and 1 M,
      and pH between 4.0 and 7.0. The emulsion heating is performed at 85 degrees C,
      which is above the denaturing temperature of BLG. The results show that, at
      C(BLG) > or = 0.04 wt %, C(EL) > or = 150 mM, and pH > or = 6.2, the heating
      leads to higher protein adsorption and to irreversible attachment of the adsorbed
      molecules, which results in enhanced steric repulsion between the protein
      adsorption multilayers and to higher emulsion stability. At low electrolyte
      concentration, C(EL) < or = 10 mM, the emulsion stability is determined by
      electrostatic interactions and is not affected significantly by the emulsion
      heating. The latter result is explained by electrostatic repulsion between the
      adsorbed protein molecules, which keeps them separated from each other and thus
      precludes the formation of disulfide covalent bonds in the protein adsorption
      layer. The coalescence stability of heated and nonheated emulsions is practically
      the same and does not depend on C(EL), when pH is around the isoelectric point
      (IEP) of the protein molecules. This is explained with the adsorption of
      uncharged BLG molecules, in compact conformation, which stores the reactive
      sulfhydryl groups hidden inside the molecule interior, thus preventing the
      formation of covalent intermolecular bonds upon heating. We studied also the
      effect of storage time on the stability of heated and nonheated emulsions. The
      stability of nonheated emulsions (C(BLG) = 0.1 wt %, C(EL) > or = 150 mM, and pH
      = 6.2) significantly decreases after 1 day of storage (aging effect). In
      contrast, no aging effect is observed after emulsion heating. FTIR spectra of
      heated and nonheated, fresh and aged emulsions suggest that the aging effect is
      caused by slow conformational changes of the protein molecules in the adsorption
      layer, accompanied with partial loss of the ordered secondary structure of the
      protein and with the formation of lateral noncovalent bonds (H-bonds and
      hydrophobic interactions) between the adsorbed molecules. After thermal treatment
      of the BLG emulsions, the molecules preserve their original secondary structure
      upon storage, which eliminates the aging effect.

PMID- 16800658
TI  - The unusual micelle micropolarity of partially fluorinated gemini surfactants
      sensed by pyrene fluorescence.
AB  - New gemini surfactants having two fluorocarbon chains were prepared by refluxing
      partially fluorinated alkyl bromide with N,N,N',N'-tetramethyl-1,6-diaminohexane
      in acetonitrile. The partially fluorinated gemini surfactants containing a six
      methylene spacer chain are easily soluble in water. The critical micelle
      concentrations (cmc's) were determined by various fluorescent probe methods. The
      hydrophobicity of a CF2 group was estimated to be 1.5 times that of a CH2 group
      according to the cmc values. The micelle micropolarity of a fluorocarbon gemini
      sensed by pyrene fluorescence was unusually high, suggesting an apparent iceberg
      like environment in the location of pyrene. The significantly small micelle
      aggregation numbers of fluorinated gemini surfactants were ascertained by the
      pyrene fluorescence quenching method. The micelle ionization degree estimated by
      fluorescence quenching of 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ) gave
      tendencies similar to those of the corresponding hydrocarbon geminis.

PMID- 16800659
TI  - Self-assembled two-dimensional ordered arrays of tripod-type molecules on
      graphite.
AB  - Tripod-type molecules with long alkyl chains, 1,1,1-tris(4-alkoxyphenyl)ethanes
      with octadecyloxy or docosyloxy chains, self-assemble into two-dimensional
      crystallites on drop-casting onto the surface of highly oriented pyrolytic
      graphite. In the two-dimensional crystalline domain, the molecules are organized
      in a mortise-and-tenon motif, as revealed by scanning tunneling microscopy. The
      time evolution of the crystallite formation has been followed by the dynamic
      force mode atomic force microscopy. The tripods may be used as a basis for the
      extension of a two-dimensional order into three-dimensional molecular
      architectures.

PMID- 16800660
TI  - Small-angle neutron scattering study of concentrated colloidal dispersions: the
      electrostatic/steric composite interactions between colloidal particles.
AB  - Small-angle neutron scattering was used to investigate the interactions in
      concentrated colloidal dispersions containing silica or polystyrene latex with
      adsorbed polyethyleneoxide (PEO). In these dispersions of charged particles, both
      electrostatic and steric repulsions are present. The PEO layer was made invisible
      to neutrons through contrast matching. The effect of the interparticle repulsion
      was clearly shown in the scattering spectra by the appearance of a peak at low Q.
      The effective potentials can be well described by the Hayter-Penfold/Yukawa (HPY)
      potential. In the silica dispersions studied, the layer thickness is small, hence
      the electrostatic potential dominates and the potential has a lower concentration
      dependence. In the dispersions of polystyrene latex, the adsorbed layer is
      thicker; consequently, the electrostatic potential dominates at low volume
      fraction (the potential has a lower concentration dependence), and the steric
      potential dominates at higher volume fraction (the potential has a higher
      concentration dependence). This study also suggests that when more than one
      potential is present the stronger one has a dominant influence in determining the
      structure factor. This finding makes it possible to describe the
      multicomponential interactions by a single function.

PMID- 16800661
TI  - Different properties of H2O- and D2O-containing phospholipid-based reverse
      micelles near a critical temperature.
AB  - Dipalmitoylphosphatidylcholine (DPPC)/water/pyridine reverse micelles have been
      found to transform from a clear liquid into a glass when the DPPC-to-water volume
      fraction is in the 0.78-0.89 range at 28 or 26 degrees C depending on whether
      water is H2O or D2O. Their study by SANS, FT-IR, and 1H NMR for this composition
      has shown remarkable effects of the isotopic nature of water on their structural
      and dynamic properties. By SANS, between 38 and 43.5 degrees C, micelles appear
      as either flexible polymer-like cylinders or short rods depending on whether
      water is H2O or D2O. On the basis of this dual aspect, micelles have been
      visualized as branched cylinders whose quasi-spherical branching points would be
      prone to assemble into short rods. In addition, when water contains more than 40%
      of D2O, a Bragg reflection emerges at 0.12 A(-1) on SANS spectra, evidencing an
      organization of micelles. In addition, FT-IR spectra show that DPPC phosphate
      groups are D bonded only when water is D2O. Consequently, we assumed that forces
      prone to organize the D2O-containing micelles are D-bonded water bridges between
      neighboring micelles at the level of their branching points. In fact, ab initio
      calculations have shown that water dimers are more stable when the bridging atom
      is D rather than H. These water bridges could be formed due to the fact that
      branching points, able to slide along micelles, keep close for a longer time when
      water is D2O than when it is H2O. Indeed, it has been shown experimentally that
      the lateral diffusion of phospholipid molecules in any layer is slower in the
      first case. Formation of such bridges triggers a deuteron migration between
      micelles evidenced by the 1/T1 relaxation rate of deuterons of water in D2O
      containing micelles measured at 43 degrees C by 1H NMR.

PMID- 16800662
TI  - Structure of self-assembled multilayers prepared from water-soluble
      polythiophenes.
AB  - We have studied the structure and morphology of self-assembled polyelectrolyte
      multilayers prepared using poly(styrenesulfonate) (PSS) and four different
      cationic poly(alkoxythiophene) derivatives bearing methylimidazolium-terminated
      ionic side chain at the 3-position of the thiophene ring: poly(1-methyl-3-[3-[3
      thienyloxy]-propyl]-1H-imidazolium) (P3TOPIM), poly(1-methyl-3-[6-[3-thienyloxy]
      hexyl]-1H-imidazolium) (P3TOHIM), poly(1-methyl-3-[2-[(4-methyl-3-thienyl)oxy]
      ethyl]-1H-imidazolium ) (P4Me-3TOEIM), and poly(1-methyl-3-[6-[(4-methyl-3
      thienyl)oxy]-hexyl]-1H-imidazolium ) (P4Me-3TOHIM). All the multilayers exhibited
      regular growth. The thickness of the multilayers was measured with ellipsometry,
      their layer-by-layer growth was followed by polarization modulation infrared
      reflection-absorption spectroscopy (PM-IRRAS) and ellipsometry, and the
      morphology of the films was studied by atomic force microscopy (AFM). The length
      of the methylimidazolium-terminated side chain (C(n), n = 2, 3, 6) and the
      substituent (H or Me) at the 4-position of the thiophene ring were varied. All
      multilayers were inhomogeneous in the sub-micrometer scale and contained
      aggregates of two kinds. The large ones with a low and constant surface number
      density were attributed to PSS, whereas the small aggregates were polythiophene
      based. The surface density of these organic semiconducting nanoparticles greatly
      depended on the structure of polythiophene, being favored by polymer
      regioregularity and the length of the side chain. The side chains remained
      disordered in all the multilayers, but with polythiophenes having hexyl chains
      both the imidazolium and thiophene rings tended to orient themselves more
      perpendicular to the surface than in films containing shorter chains (C2 or C3).
      The relative water content of the multilayers (at 7.1% relative humidity) did not
      depend on the film thickness and was the lowest for P4Me-3TOHIM. As the number of
      bilayers increased the methylimidazolium-sulfonate ion pairs gradually weakened
      and became more individually hydrated.

PMID- 16800663
TI  - Charging behavior of the gibbsite basal (001) surface in NaCl solution
      investigated by AFM colloidal probe technique.
AB  - The charging behavior of the gibbsite gamma-Al(OH)3 basal (001) surface in
      aqueous solution is important for correctly modeling the overall charging
      properties of gibbsite particles which controls surface phenomena such as
      adsorption and crystal growth. However, the question of whether the hydroxyl
      groups on the basal plane are proton active has been raised recently both from
      experimental and theoretical points of view. Using gibbsite crystals prepared
      from industrial Bayer process, the surface potentials of cleaved (001) surfaces
      were calculated from forces measured by the colloidal probe technique in 1 mM
      NaCl solution with differing pH. It was surprisingly found that the basal plane
      is proton active in pH less than 7 and protonation seems to level off at about pH
      5. The potential-pH data was accurately fitted with a single pKa surface
      protonation model with pK(a) = 5.9 +/- 0.2.

PMID- 16800664
TI  - Direct determination of the thermodynamics of polyelectrolyte complexation and
      implications thereof for electrostatic layer-by-layer assembly of multilayer
      films.
AB  - Interpolyelectrolyte complex (IPEC) formation between poly(styrene sulfonate)
      (PSS) and poly(allylamine hydrochloride) (PAH) has been studied over a range of
      ionic strengths by isothermal titration calorimetry (ITC), turbidity titration,
      and electrostatic layer-by-layer assembly (ELBL). The results indicate that IPEC
      formation of PSS/PAH in aqueous solution is predominantly entropy-driven. The
      thermodynamic parameters suggest the formation of different types of complexes
      and aggregates due to salt-induced conformational changes in the polyelectrolyte
      conformation. Differences in polyelectrolyte behavior in the different salt
      concentration regimes are described in terms of changes in the Debye screening
      length of the polyelectrolytes. The relationship of the results to the effect of
      salt concentration on the assembly of polyelectrolyte multilayer films (PEMs) is
      discussed.

PMID- 16800665
TI  - Electrochemical and surface characterization of 4-aminothiophenol adsorption at
      polycrystalline platinum electrodes.
AB  - The formation of a self-assembled monolayer (SAM) of 4-aminothiophenol (4-ATP) on
      polycrystalline platinum electrodes has been characterized by surface analysis
      and electrochemistry techniques. The 4-ATP monolayer was characterized by cyclic
      voltammetry (CV), linear sweep voltammetry, Raman spectroscopy, reflection
      absorption infrared (RAIR) spectroscopy, and X-ray photoelectron spectroscopy
      (XPS). CV was used to study the dependence of the adsorption time and 4-ATP
      solution concentration on the relative degree of coverage of 4-ATP monolayers on
      polycrystalline Pt electrodes. The adsorption time range probed was 24-72 h. The
      optimal concentration of 4-ATP needed to obtain the highest surface at the lowest
      adsorption time was 10 mM. RAIR and Raman spectroscopy for 4-ATP-modified
      platinum electrodes showed the characteristic adsorption bands for 4-ATP, such as
      nuNH, nuCH(arom), and nuCS(arom), indicating the adsorption on the platinum
      surface. The XPS spectra for the modified Pt surface presented the binding energy
      peaks of sulfur and nitrogen. High energy resolution XPS studies, RAIR, and Raman
      spectrum for platinum electrodes modified with 4-ATP indicate that the molecules
      are sulfur-bonded to the platinum surface. The formation of a S-Pt bond suggests
      that ATP adsorption leads to an amino-terminated electrode surface. The thickness
      of the monolayer was evaluated via angle-resolved XPS (AR-XPS) analyses, giving a
      value of 8 A. As evidence of the terminal amino group on the electrode surface,
      the chemical derivatization of the 4-ATP SAM was done with 16-Br hexadecanoic
      acid. This surface reaction was followed by RAIR spectroscopy.

PMID- 16800666
TI  - Surface modification of EPDM rubber by plasma treatment.
AB  - The effect of argon, oxygen, and nitrogen plasma treatment of solvent cast EPDM
      rubber films has been investigated by means of atomic force microscopy (AFM), X
      ray photoelectron spectroscopy (XPS), and surface energy measurements. Plasma
      treatment leads to changes in the surface energy from 25 to 70 mN/m. Treatment
      conditions influenced both the changes in surface energy and the stability, and
      it became more difficult to obtain good contact angle measurements after longer
      (> ca. 4 min) treatment times, probably because of an increasingly uneven surface
      structure. XPS analyses revealed that up to 20 at. % oxygen can be easily
      incorporated and that variations of approximately 5% can be controlled by the
      plasma conditions. Oxygen was mainly found in hydroxyl groups, but also as
      carbonyl and carboxyl. XPS analyses showed more stable surfaces than expected
      from contact angles, probably because XPS analysis is less surface sensitive than
      contact angle measurements. AFM measurements revealed different surface
      structures with the three gases. The surface roughness increased generally with
      treatment time, and dramatic changes could be observed at longer times. At short
      times, surface energy changes were much faster than the changes in surface
      structure, showing that plasma treatment conditions can be utilized to tailor
      both surface energies and surface structure of EPDM rubber.

PMID- 16800667
TI  - Double hydrophilic block copolymer controlled growth and self-assembly of CaCO3
      multilayered structures at the air/water interface.
AB  - Double hydrophilic block copolymers PEG-b-PEI-linear with different PEI block
      lengths have been examined for CaCO3 mineralization at the air/water interface.
      The results demonstrated that either PEI length or the solution acidity had a
      significant influence on the morphogenesis of vaterite crystals at the air/water
      interface. A possible mechanism for the stratification of CaCO3 vaterite crystals
      has been proposed. Increasing either PEI length or the initial pH value of the
      solution will decrease the density of the PEG block anchored on the binding
      interface and result in exposing more space as binding interface to solution and
      favoring the subnucleation and stratification growth on the polymer-CaCO3
      interface. In contrast, higher density of PEG blocks will stabilize the growing
      crystals more efficiently and inhibit subnucleation on the polymer-CaCO3
      interface, and thus prevent the formation of stratified structures. This study
      provides an example that it is possible to access morphogenesis of calcium
      carbonate structures by a combination of a block copolymer with the air/water
      interface.

PMID- 16800668
TI  - Implications of the contact radius to line step (CRLS) ratio in AFM for
      nanotribology measurements.
AB  - Investigating the mechanisms of defect generation and growth at surfaces on the
      nanometer scale typically requires high-resolution tools such as the atomic force
      microscope (AFM). To accurately assess the kinetics and activation parameters of
      defect production over a wide range of loads (F(z)), the AFM data should be
      properly conditioned. Generally, AFM wear trials are performed over an area
      defined by the length of the slow (L(sscan)) and fast scan axes. The ratio of
      L(sscan) to image resolution (res, lines per image) becomes an important
      experimental parameter in AFM wear trials because it defines the magnitude of the
      line step (LS = L(sscan)/res), the distance the AFM tip steps along the slow scan
      axis. Comparing the contact radius (a) to the line step (LS) indicates that the
      overlap of successive scans will result unless the contact radius-line step ratio
      (CRLS) is < or =(1)/(2). If this relationship is not considered, then the scan
      history (e.g., contact frequency) associated with a single scan is not equivalent
      at different loads owing to the scaling of contact radius with load (a
      proportional variant F(z)(1/3)). Here, we present a model in conjunction with
      empirical wear tests on muscovite mica to evaluate the effects of scan overlap on
      surface wear. Using the Hertz contact mechanics definition of a, the CRLS model
      shows that scan overlap pervades AFM wear trials even under low loads. Such
      findings indicate that simply counting the number of scans (N(scans)) in an
      experiment underestimates the full history conveyed to the surface by the tip and
      translates into an error in the actual extent to which a region on the surface is
      contacted. Utilizing the CRLS method described here provides an approach to
      account for image scan history accurately and to predict the extent of surface
      wear. This general model also has implications for any AFM measurement where one
      wishes to correlate scan-dependent history to image properties as well as feature
      resolution in scanned probe lithographies.

PMID- 16800669
TI  - Forces between mica surfaces, prepared in different ways, across aqueous and
      nonaqueous liquids confined to molecularly thin films.
AB  - We have measured normal and lateral interactions across a range of different
      liquids between mica surfaces using a surface force balance (SFB). The mica
      surfaces were prepared either by melt cutting using Pt wire and standard
      procedures in our laboratories or by tearing sheets (that had not been exposed to
      Pt) off from a freshly cleaved sheet of mica. AFM micrographs revealed the
      substantial absence of Pt nanoparticles on the melt cut and torn-off mica
      surfaces. Normal-force versus surface-separation (D) profiles and shear force
      versus D measurements for purified water (no added salt), for concentrated
      aqueous NaCl solutions, and for cyclohexane revealed that in all cases the
      behavior of the highly confined liquids between melt-cut and between torn-off
      mica sheets was identical within experimental scatter. These results demonstrate
      directly that interactions measured between melt-cut mica surfaces as routinely
      prepared using established procedures in our laboratories and in other
      laboratories are free of the effect of any Pt contamination.

PMID- 16800670
TI  - Neutron reflection study of a water-soluble biocompatible diblock copolymer
      adsorbed at the air/water interface: the effects of pH and polymer concentration.
AB  - The effect of varying both the solution pH and copolymer concentration on the
      structure of layers of poly[2-(methacryloyloxy)ethyl phosphorylcholine-block-2
      (dimethylamino)ethyl methacrylate] copolymer (denoted as MPC(30)-DMA(60), M(n) =
      18,000) adsorbed at the air/water interface is studied using surface tension and
      specular neutron reflection. The surface structure of the adsorbed diblock
      copolymer is represented by a dense layer of 10-15 A on the air side, accompanied
      by a loose layer of 20-30 A extending into the aqueous phase. Although the
      uniform layer model generally provided a reasonable description of the adsorbed
      copolymer chains, some deviations were observed. A more detailed analysis showed
      that the distribution of the copolymer across the interface required a minimum of
      three layers to take into account the structural inhomogeneities. Refinement of
      the structural distributions involved the combined fitting of partially
      deuterated copolymer in null reflecting water and D(2)O and the fully
      hydrogenated copolymer in D(2)O, leading to a substantial improvement in the
      reliability of the structural profiles obtained. The data analysis showed an
      increase in surface excess at higher copolymer concentrations and at more
      alkaline pH. However, the copolymer layer was fully immersed in water under all
      conditions studied. Because the surface excess showed a steady increase across
      the cmc over the high pH range, we speculate that copolymer adsorption above the
      cmc involves the formation of surface micellar aggregates under these conditions.

PMID- 16800672
TI  - Surface morphologies of Langmuir-Blodgett monolayers of PEOnPSn multiarm star
      copolymers.
AB  - Star polymers composed of equal numbers of poly(ethylene oxide) (PEO) and
      polystyrene (PS) arms with variable lengths and a large (up to 38 total) number
      of arms, PEO(n)PS(n), have been examined for their ability to form domain
      nanostructures at the air-water and air-solid interfaces. All PEO(n)PS(n) star
      polymers formed stable Langmuir-Blodgett (LB) monolayers transferable to a solid
      substrate. A range of nanoscale surface morphologies have been observed, ranging
      from cylindrical to circular domains to bicontinuous structures as the weight
      fraction of the PEO block varied from 19% to 88% and n from 8 to 19. For the PS
      rich stars and at elevated surface pressure, a two-dimensional supramolecular
      netlike nanostructure was formed. In contrast, in the PEO-rich star polymer with
      the highest PEO content, we observed peculiar dendritic superstructures caused by
      intramolecular segregation of nonspherical core-shell micellar structures. On the
      basis of Langmuir isotherms and observed monolayer morphologies, three different
      models of possible surface behavior of the star polymers at the interfaces were
      proposed.

PMID- 16800671
TI  - Directing droplets using microstructured surfaces.
AB  - Systematic variation of microscale structures has been employed to create a rough
      superhydrophobic surface with a contact angle gradient. Droplets are propelled
      down these gradients, overcoming contact angle hysteresis using energy supplied
      by mechanical vibration. The rough hydrophobic surfaces have been designed to
      maintain air traps beneath the droplet by stabilizing its Fakir state. Dimensions
      and spacing of the microfabricated pillars in silicon control the solid-liquid
      contact area and are varied to create a gradient in the apparent contact angle.
      This work introduces the solid-liquid contact area fraction as a new control
      variable in any scheme of manipulating droplets, presenting theory, fabricated
      structures, and experimental results that validate the approach.

PMID- 16800673
TI  - The role of Azopolymer/Dendrimer layer-by-layer film architecture in photoinduced
      birefringence and the formation of surface-relief gratings.
AB  - The fabrication of nanostructured layer-by-layer (LbL) films strives for
      molecular control of the film properties directly connected with modifications in
      the film architecture. In the present report, the photoinduced birefringence and
      formation of the surface-relief gratings in LbL films obtained with an azopolymer
      (PS119) are shown to be strongly affected by the generation of the dendrimer
      employed in the alternating layers. Stronger adsorption of PS119 occurred when
      polypropylenimine tetrahexacontaamine dendrimer (DAB) of higher generations is
      used, due to a larger number of sites available to interact with azochromophores
      in PS119. In contrast, the photoinduced birefringence for LbL films made with the
      generation 1 dendrimer (DABG1) was higher, which can be explained by weaker
      interactions between adjacent layers. Strong interactions in LbL films consisting
      of PS119 and generation 3 or 5 dendrimers restrict the chromophore mobility,
      leading to a smaller birefringence. The interpretation is supported by the fact
      that surface-relief gratings with larger amplitudes were obtained for 35-bilayer
      films of DABG1/PS119 (31 nm) in comparison with films from DABG5/PS119 (5 nm).
      These gratings were formed with mass transport arising from a light-driven
      mechanism, as photoinscription was successful only with p-polarized light and not
      with s-polarized light.

PMID- 16800674
TI  - Compression/expansion rheology of oil/water interfaces with adsorbed proteins.
      Comparison with the air/water surface.
AB  - Dynamic interfacial tensions and surface dilational moduli were measured for four
      proteins at three fluid interfaces, as a function of time and concentration. The
      proteins-beta-casein, beta-lactoglobulin, bovine serum albumin, and ovalbumin
      were adsorbed from aqueous solution against air, n-tetradecane, and a
      triacylglycerol oil. The sinusoidal interfacial compression/expansion, at
      frequencies ranging from 0.005 to 0.5 Hz, was effected in a dynamic drop
      tensiometer suited to viscous oil phases. Generally, at interfacial pressures up
      to 15 mN/m, dilational moduli were purely elastic at frequencies from 0.1 Hz. In
      this elastic range, in-surface relaxation either was essentially completed or had
      not yet started within a time on the order of 10 s. Within this time span,
      protein exchange with the bulk solution was negligible. In cases where in-surface
      relaxation was completed in the imposed time, the moduli depended only on the
      equilibrium Pi(Gamma) relationship. We interpret these results in terms of a
      simple two-dimensional solution model, based on a Gibbs dividing surface,
      accounting for nonideal mixing to the first order with respect to both entropy
      and enthalpy. Interfacial mixing enthalpy is shown to have a major effect on the
      elasticity, with both quantities increasing in the sequence triacylglycerol <
      tetradecane < air. We also suggest a strong correlation between enthalpy and
      clean-interface tension that increases in the same order. At each interface, the
      enthalpy increases with increasing molecular rigidity: beta-casein < beta
      lactoglobulin < bovine serum albumin < ovalbumin. Best agreement with the
      experimental data was obtained with a recently extended version of the model
      accounting for proteins adopting smaller molecular areas with increasing surface
      pressure. For interfacial pressures above 15 mN/m, the moduli were generally no
      longer purely elastic, with viscous loss angles ranging up to 36 degrees. In this
      range of high pressures, the moduli depended on relaxation mechanisms for which
      specific kinetic models must be developed.

PMID- 16800675
TI  - Molecular dynamics simulation study of the structure of poly(ethylene oxide)
      brushes on nonpolar surfaces in aqueous solution.
AB  - The structure of poly(ethylene oxide) (PEO, M(w) = 526) brushes of various
      grafting density (sigma) on nonpolar graphite and hydrophobic (oily) surfaces in
      aqueous solution has been studied using atomistic molecular dynamics simulations.
      Additionally, the influence of PEO-surface interactions on the brush structure
      was investigated by systematically reducing the strength of the (dispersion)
      attraction between PEO and the surfaces. PEO chains were found to adsorb strongly
      to the graphite surface due primarily to the relative strength of dispersion
      interactions between PEO and the atomically dense graphite compared to those
      between water and graphite. For the oily surface, PEO-surface and water-surface
      dispersion interactions are much weaker, greatly reducing the energetic driving
      force for PEO adsorption. This reduction is mediated to some extent by a
      hydrophobic driving force for PEO adsorption on the oily surface. Reduction in
      the strength of PEO-surface attraction results in reduced adsorption of PEO for
      both surfaces, with the effect being much greater for the graphite surface where
      the strong PEO-surface dispersion interactions dominate. At high grafting density
      (sigma approximately 1/R(g)(2)), the PEO density profiles exhibited classical
      brush behavior and were largely independent of the strength of the PEO-surface
      interaction. With decreasing grafting density (sigma < 1/R(g)(2)), coverage of
      the surface by PEO requires an increasingly large fraction of PEO segments
      resulting in a strong dependence of the PEO density profile on the nature of the
      PEO-surface interaction.

PMID- 16800676
TI  - Miscibility of binary monolayers at the air-water interface and interaction of
      protein with immobilized monolayers by surface plasmon resonance technique.
AB  - The miscibility and stability of the binary monolayers of zwitterionic
      dipalmitoylphosphatidylcholine (DPPC) and cationic dioctadecyldimethylammonium
      bromide (DOMA) at the air-water interface and the interaction of ferritin with
      the immobilized monolayers have been studied in detail using surface pressure
      area isotherms and surface plasmon resonance technique, respectively. The surface
      pressure-area isotherms indicated that the binary monolayers of DPPC and DOMA at
      the air-water interface were miscible and more stable than the monolayers of the
      two individual components. The surface plasmon resonance studies indicated that
      ferritin binding to the immobilized monolayers was primarily driven by the
      electrostatic interaction and that the amount of adsorbed protein at saturation
      was closely related not only to the number of positive charges in the monolayers
      but also to the pattern of positive charges at a given mole fraction of DOMA. The
      protein adsorption kinetics was determined by the properties of the monolayers
      (i.e., the protein-monolayer interaction) and the structure of preadsorbed
      protein molecules (i.e., the protein-protein interaction).

PMID- 16800677
TI  - Assembly dynamics and detailed structure of 1-propanethiol monolayers on Au(111)
      surfaces observed real time by in situ STM.
AB  - 1-Propanethiol is chosen as a model alkanethiol to probe detailed mechanisms of
      the self-assembled monolayer (SAM) formation at aqueous/Au(111) interfaces. The
      assembly processes, including initial physi- and chemisorption, pit formation,
      and domain growth, were recorded into movies in real-time with high resolution by
      in situ scanning tunneling microscopy (STM) under potential control. Two major
      adsorption steps were disclosed in the propanethiol SAM formation. The first step
      involves weak interactions accompanied by the lift of the Au(111) surface
      reconstruction, which depends reversibly on the electrochemical potentials. The
      second step is chemisorption to form a dense monolayer, accompanied by formation
      of pits as well as structural changes in the terrace edges. Pits emerged at the
      stage of the reconstruction lift and increased to a maximum surface coverage of
      4.0 +/- 0.4% at the completion of the SAM formation. Well-defined triangular pits
      in the SAM were found on the large terraces (more than 300 nm wide), whereas few
      and small pinholes appeared at the terrace edge areas. Smooth edges were
      converted into saw-like structural features during the SAM formation, primarily
      along the Au(111) atomic rows. These observations suggest that shrinking and
      rearrangement of gold atoms are responsible for both formation of the pits and
      the shape changes of the terrace edges. STM images disclose a (2 square root 3 x
      3)R30 degrees periodic lattice within the ordered domains. Along with
      electrochemical measurements, each lattice unit is assigned to contain four
      propanethiol molecules exhibiting different electronic contrasts, which might
      originate in different surface orientations of the adsorbed molecules.

PMID- 16800678
TI  - Trapping silicon surface-based radicals.
AB  - The spontaneous one-electron reduction of diazonium salts on hydride-terminated
      porous silicon (pSi) and flat silicon produces surface radicals that can be
      trapped chemically. These silicon radicals react with reagents such as
      alkyl/arylselenoethers, alkenes, alkynes, and alkylbromide groups to generate
      covalently bound functionalities in a manner analogous to the chemistry of
      molecular-based silicon radical species, prepared via different methods. When pSi
      is exposed to an acetonitrile solution of any of the three diazonium salts
      examined in this study, aryl groups from the diazonium precursor become
      covalently bound and significant oxidation is noted; if, however, a reactive
      trapping agent is added, such as an alkyl/arylselenoether or a carbon-carbon
      unsaturated bond, no aryl group attachment is observed and oxidation is
      circumvented due to the efficiency of the trapping chemistry. The reactions
      proceed rapidly, in less than 3 h to maximum coverage, at room temperature. The
      diazonium salt-initiated radical reaction with alpha,omega-alkenes and alkynes
      tolerates various functional groups including aryl, diene, diyne, carboxylic
      acid, and hydroxyl, reacting exclusively via the carbon-carbon unsaturated bond;
      alpha,omega-bromoalkenes are not, however, compatible with this chemistry. A
      silicon-based molecule, tris(trimethylsilyl)silane, in the presence of a
      diazonium salt initiator and a primary alkyne does not lead to the
      hydrosilylation product but to tris(trimethylsilyl)silylbromide and the
      hydrogenated arene, derived from the diazonium. The difference in reactivity
      between the molecule and the surface is due to the fact that the silicon surface
      is a source of electrons to reduce the diazonium salts to aryl radicals, whereas
      a heterolytic pathway is followed in the molecular silane case.

PMID- 16800679
TI  - Coupling vs surface-etching reactions of alkyl halides on GaAs(100). 2. CH2I2
      reactions.
AB  - Surface reactions of CH2I2 on gallium-rich GaAs(100)-(4 x 1), studied by
      temperature programmed desorption and X-ray photoelectron spectroscopy (XPS),
      show CH2I2 adsorbs dissociatively at liquid nitrogen temperatures to form surface
      chemisorbed CH2(ads) and I(ads) species. Controlled hydrogenation of a fraction
      of the CH2(ads) species in the chemisorbed layer by the background hydrogen
      radicals results in a surface layer comprising both CH3(ads) and CH2(ads)
      species. This hydrogenation step initiates a plethora of further surface
      reactions involving these two species and I(ads). Thermal activation leads to
      three sequential methylene insertions (CH2(ads)) into the CH3-surface bond to
      form three higher alkyl (ethyl (C2), propyl (C3), and butyl (C4)) species, which
      undergo beta-hydride elimination to evolve the respective higher alkene (ethene,
      propene, and butene). In competition with beta-hydride elimination, reductive
      elimination of the ethyl and propyl species with I(ads) occurs to liberate the
      respective alkyl iodide. Beta-hydride elimination in the alkyls, in the
      temperature range 420-520 K, is the more dominant pathway, and it is also the
      rate-limiting step for further chain propagation. The evolution of the alkyl
      iodides represents the only pathway for the removal of surface iodines in this
      study and is different from previous investigations where gallium and arsenic
      iodide etch products (GaI(x), AsI(x) (x = 1-3)) formed instead. The desorption of
      methane and methyl iodide, formed from surface CH3(ads) species at high
      temperatures by the reaction between surface methylenes and hydrogens eliminated
      from the surface C2-C4 alkyls, terminates the chain propagation. We discuss the
      reaction mechanisms by which the observed reaction products form and postulate
      reasons for the reaction pathways adopted by the surface species.

PMID- 16800680
TI  - Contact angle hysteresis explained.
AB  - A view of contact angle hysteresis from the perspectives of the three-phase
      contact line and of the kinetics of contact line motion is given. Arguments are
      made that advancing and receding are discrete events that have different
      activation energies. That hysteresis can be quantified as an activation energy by
      the changes in interfacial area is argued. That this is an appropriate way of
      viewing hysteresis is demonstrated with examples.

PMID- 16800681
TI  - Features of nitrogen adsorption on nonporous carbon and silica surfaces in the
      framework of classical density functional theory.
AB  - Equilibrium adsorption data of nitrogen on a series of nongraphitized carbon
      blacks and nonporous silica at 77 K were analyzed by means of classical density
      functional theory to determine the solid-fluid potential. The behavior of this
      potential profile at large distance is particularly considered. The analysis of
      nitrogen adsorption isotherms seems to indicate that the adsorption in the first
      molecular layer is localized and controlled mainly by short-range forces due to
      the surface roughness, crystalline defects, and functional groups. At distances
      larger than approximately 1.3-1.5 molecular diameters, the adsorption is
      nonlocalized and appears as a thickening of the adsorbed film with increasing
      bulk pressure in a relatively weak adsorption potential field. It has been found
      that the asymptotic decay of the potential obeys the power law with the exponent
      being -3 for carbon blacks and -4 for silica surface, which signifies that in the
      latter case the adsorption potential is mainly exerted by surface oxygen atoms.
      In all cases, the absolute value of the solid-fluid potential is much smaller
      than that predicted by the Lennard-Jones pair potential with commonly used solid
      fluid molecular parameters. The effect of surface heterogeneity on the heat of
      adsorption is also discussed.

PMID- 16800682
TI  - X-ray reflectivity study of ultrathin liquid films of diphenylsiloxane
      dimethylsiloxane copolymers.
AB  - Using X-ray reflectivity, we observe drastic differences in the interfacial
      structure and molecular ordering of diphenylsiloxane-dimethylsiloxane copolymer
      thin films deposited on hydroxylated versus H-terminated (etched) silicon wafers.
      We find that substrate type and comonomer ratio determine the conformational
      arrangements in these liquid films. High-energy bonding between the substrate and
      the molecules and an increase in rigidity of the molecules due to replacement of
      methyl groups by phenyl groups leads to a specific molecular ordering at the
      liquid/solid interface and pronounced density oscillations in this region. The
      observed structural reorganizations are explained by the interplay and the
      established balance between the chain flexibility and the polymer-substrate
      interactions.

PMID- 16800683
TI  - Phenylphosphonic acid functionalization of indium tin oxide: surface chemistry
      and work functions.
AB  - The work function of indium tin oxide (ITO) substrates was modified with
      phosphonic acid molecular films. The ITO surfaces were treated prior to
      functionalization with a base cleaning procedure. The film growth and coverage
      were quantified by contact angle goniometry and XPS. Film orientation was
      determined by reflection/absorption infrared spectroscopy using ITO-on-Cr
      substrates. The absolute work functions of nitrophenyl- and cyanophenyl
      phosphonic acid films in ITO were determined by Kelvin probe measurement to be
      5.60 and 5.77 eV, respectively.

PMID- 16800684
TI  - Effects of DNA on the growth and optical properties of luminescent organic
      microcrystals.
AB  - The reprecipitation method, which is a solvent-exchange process, was used to
      prepare free-standing microcrystals from an organic fluorescent dye, 4-n
      octylamino-7-nitrobenz-2-oxa-1,3-diazole. Calf thymus DNA was introduced as an
      additive into the reprecipitation medium, strongly accelerating the process. The
      reprecipitation kinetics was monitored by UV/vis absorption spectroscopy, and the
      analysis of the rate constants allowed the role played by the additive to be
      clarified. DNA was also found to affect the shape and size of the dye
      microcrystals obtained. In particular, its presence induced the formation of a
      new type of microcrystal that displays original two-color fluorescence. The
      emission properties were first analyzed on the suspensions, using a traditional
      fluorimeter, and then on individual microcrystals by means of a space- and time
      correlated photon-counting photomutiplier installed on a microscope. The study on
      single microcrystals suggests that the dual coloration observed originates from
      the reabsorption of the blue component of the emitted light, whereas the
      remaining red component propagates through the microcrystal body and is scattered
      by the edges. However, the color of the other types of microcrystals can be
      explained only by specific arrangements of molecules at the surface of the
      crystal.

PMID- 16800685
TI  - In situ three-dimensional characterization of membrane fouling by protein
      suspensions using multiphoton microscopy.
AB  - Fouling of microfiltration membranes leads to severe flux declines and the need
      to clean or replace the membrane. In situ 3D characterization of protein fouling
      both on the surface and within the pores of the membrane was achieved using
      multiphoton microscopy. Time-lapse images of the fouled membrane were obtained
      for single suspensions and mixtures of fluorescently labeled bovine serum albumin
      and ovalbumin. Deposited protein aggregates were visible on the membrane and
      evidently play an important role in fouling. A combination of 3D images and
      resistance versus time data was used to identify the dominant fouling mechanism.
      Fouling is initially internally dominated, but after 1 and 15 min for ovalbumin
      and bovine serum albumin, respectively, the fouling becomes externally dominated.
      This is in good agreement with two-stage protein fouling models.

PMID- 16800686
TI  - Visualizing the solubilization of supported lipid bilayers by an amphiphilic
      peptide.
AB  - The effect of the presequence peptide of cytochrome c oxidase subunit IV (p25) on
      supported phospholipid bilayers (SPBs) was visualized using atomic force
      microscopy (AFM). The presequence was found to cause the complete disruption of
      supported bilayers containing neutral lipids. At relatively low concentrations of
      presequence, the peptide was found to bind to the membrane, coalescing to form
      microdomains within the liquid-crystalline bilayer that were located
      predominantly at bilayer-mica boundaries. Further increases in peptide
      concentration resulted in the formation of holes within the SPB that were spanned
      by an interpenetrating network of narrower regions of the bilayer, which, at
      higher applied peptide concentrations, were observed to disappear through a
      budding process, ultimately leading to the formation of spherical structures at
      yet higher peptide concentrations. Within this paper, the impact the presequence
      has upon the structure and order of the membrane is discussed, as is the
      potential implication of this apparent solubilization process on the
      translocation of cytochrome c oxidase into the inner mitochondrial membrane.

PMID- 16800687
TI  - Electric potential induced dissociation of hybridized DNA with hairpin motif
      immobilized on silicon surface.
AB  - DNA probes were immobilized on silicon surfaces through ester condensation
      between the -COOH group on the surface and the terminal -OH group in the
      oligonucleotide, and the surface density of DNA probes against the concentration
      of immobilization solution was measured by radioactive labeling. The dissociation
      of DNA duplex on the surface by an electric potential was studied with the
      scanning potential hairpin denaturation/dissociation (SPHD). The influence of the
      stem length in the hairpin probe on the SPHD curve was systematically
      investigated. It was found that the capability of discrimination on single
      nucleotide polymorphism (SNP) by a hairpin probe was related to the free energy
      of formation of the secondary structure in the probe (DeltaG(ss)). In our system,
      when DeltaG(ss) was around -3 kcal/mol, an optimal recognition of SNP was reached
      and the SPHD curve was sigmoid. In contrast, the equivalent SPHD curve from a
      linear probe was exponential-decay alike with a poor discrimination of SNP. The
      concentration dependent experiments showed good linearity between the melting
      potential and logarithm of target concentration in the range of 1 x 10(-9) to 5 x
      10(-7) M.

PMID- 16800688
TI  - Selective protein adsorption on a phase-separated solvent-cast polymer blend.
AB  - Polymer-based biomedical devices are growing increasingly sophisticated as
      compositions evolve toward copolymers and blends in order to satisfy complex
      design criteria. Such polymers afford opportunities for both micro- and
      macrophase separation at nano- and micro-length scales and raise questions
      concerning the role of heterogeneous surface morphology on protein adsorption.
      Adsorbed protein layers play a critical role in mediating the interaction of
      cells with polymer surfaces, and both understanding and controlling protein
      adsorption is assuming greater significance in the development of surfaces with
      enhanced physiological compatibility. Here we study the short-time adsorption of
      ferritin, a model protein highly resistant to denaturation and easily imaged in
      the transmission electron microscope (TEM), onto a phase-separated homopolymer
      blend of polycaprolactone (PCL) and a polycarbonate derived from desaminotyrosyl
      tyrosine dodecyl ester (PDTD). At physiological pH, ferritin selectively adsorbs
      onto the PDTD phase at a surface density approximately three times greater than
      that on the PCL phase. By decreasing the pH below ferritin's isoelectric point so
      its average charge becomes positive, the selective adsorption disappears and the
      surface density of adsorbed ferritin becomes independent of the phase separation.
      We attribute the selectivity to the electrostatic repulsion between ferritin and
      hydrolytically charged PCL, both of which will have a net negative charge at
      physiological pH. To perform these experiments, we solvent-cast ultrathin polymer
      films onto dissolvable salt substrates, and we characterize the morphology by TEM
      imaging and quantitative spatially resolved electron energy-loss spectroscopy
      (EELS). We find that the film morphology depends strongly on such processing
      related variables as the solvent evaporation rate and the nature of the surface
      in contact with the polymer film during casting. The adsorption of ferritin
      depends on whether the film is phase-separated as well as to which surface of the
      film the protein solution is exposed, and these findings suggest that seemingly
      small variations in polymer processing that influence both the bulk and surface
      morphology can have a profound effect on the short-time protein adsorption.

PMID- 16800689
TI  - DNA condensation and interaction with zwitterionic phospholipids mediated by
      divalent cations.
AB  - Artificial viruses are considered to be a promising tool in gene therapy. To find
      lipid-DNA complexes with high transfection efficiency but without toxicity is a
      fundamental aim. Although cationic lipids are frequently toxic for cells, neutral
      lipids are completely nontoxic. Zwitterionic lipids do not interact with DNA
      directly; however, the interaction can be mediated by divalent cations. Langmuir
      monolayers represent a well-defined model system to study the DNA-lipid complexes
      at the air/water interface (quasi-2D systems). In this work, isotherms, infrared
      reflection absorption spectroscopy (IRRAS), X-ray reflectivity (XR), grazing
      incidence X-ray diffraction (GIXD), and Brewster angle microscopy (BAM)
      measurements are used to study the interaction of calf thymus DNA with DMPE (1,2
      dimyristoyl-phosphatidylethanolamine) monolayers mediated by Ca2+ or Mg2+ ions.
      DNA adsorption is observed only in the presence of divalent cations. At low
      lateral pressure, the DNA partially penetrates into the lipid monolayer but is
      squeezed out at high pressure. The adsorption layer has a thickness of 18-19 A.
      Additionally, GIXD provides information about a one-dimensional ordering of
      adsorbed DNA. The periodic distance between DNA strands depends on the type of
      the divalent cation.

PMID- 16800690
TI  - Immobilizing single lipid and channel molecules in artificial lipid bilayers with
      annexin A5.
AB  - The effects of annexin A5 on the lateral diffusion of single-molecule lipids and
      single-molecule proteins were studied in an artificial lipid bilayer membrane.
      Annexin A5 is a member of the annexin superfamily, which binds preferentially to
      anionic phospholipids in a Ca2+-dependent manner. In this report, we were able to
      directly monitor single BODIPY 1,2-dihexadecanoyl-sn-glycero-3
      phosphoethanolamine (DHPE) and ryanodine receptor type 2 (RyR2) labeled with Cy5
      molecules in lipid bilayers containing phosphatidylserine (PS) by using
      fluorescence microscopy. The diffusion coefficients were calculated at various
      annexin A5 concentrations. The diffusion coefficients of BODIPY-DHPE and Cy5-RyR2
      in the absence of annexin A5 were 4.81 x 10(-8) cm(2)/s and 2.13 x 10(-8)
      cm(2)/s, respectively. In the presence of 1 microM annexin A5, the diffusion
      coefficients of BODIPY-DHPE and Cy5-RyR2 were 2.2 x 10(-10) cm(2)/s and 9.5 x 10(
      11) cm(2)/s, respectively. Overall, 1 microM of annexin A5 was sufficient to
      induce a 200-fold decrease in the lateral diffusion coefficient. Additionally, we
      performed electrophysiological examinations and determined that annexin A5 has
      little effect on the function of RyR2. This means that annexin A5 can be used to
      immobilize RyR2 in a lipid bilayer when imaging and analyzing RyR2.

PMID- 16800691
TI  - Drying of DNA droplets.
AB  - The evaporation kinetics of droplets containing DNA was studied, as a function of
      DNA concentration. Drops containing very low DNA concentrations dried by
      maintaining a constant base, whereas those with high concentration dried with a
      constant contact angle. To understand this phenomenon, the distribution of the
      DNA inside the droplet was measured using confocal microscopy. The results
      indicated that the DNA was condensed mostly on the surface of the droplets. In
      the case of high concentration droplets, it formed a shell, whereas isolated
      islands were found for droplets of low DNA concentrations. Rheologic results
      indicate the formation of a hydro gel in the low concentration drops, whereas
      phase separation between the self-assembled DNA structures and the water phase
      occurred at higher concentration.

PMID- 16800692
TI  - Orientation of a monoclonal antibody adsorbed at the solid/solution interface: a
      combined study using atomic force microscopy and neutron reflectivity.
AB  - Conformational orientations of a mouse monoclonal antibody to the beta unit of
      human chorionic gonadotrophin (anti-beta-hCG) at the hydrophilic silicon
      oxide/water interface were investigated using atomic force microscopy (AFM) and
      neutron reflectivity (NR). The surface structural characterization was conducted
      with the antibody concentration in solution ranging from 2 to 50 mg.L(-1) with
      the ionic strength kept at 20 mM and pH = 7.0. It was found that the antibody
      adopted a predominantly "flat-on" orientation, with the Fc and two Fab fragments
      lying flat on the surface. The AFM measurement revealed a thickness of 30-33 A of
      the layer formed in contact with 2 mg.L(-1) antibody in water, but,
      interestingly, the flat-on antibody molecules formed small nonuniform clusters
      equivalent to 2-15 antibody molecules. Parallel AFM scanning in air revealed even
      larger surface clusters, suggesting that surface drying induced further
      aggregation. The AFM study thus demonstrated that the interaction between protein
      and the hydrophilic surface is weak and indicated that surface aggregation can be
      driven by the attraction between neighboring protein molecules. NR measurements
      at the solid/water interface confirmed the flat-on layer orientation of adsorbed
      molecules over the entire concentration range studied. Thus, at 2 mg.L(-1), the
      adsorbed antibody layer was well represented by a uniform layer with a thickness
      of 40 A. This value is thicker than the 30-33 A observed from AFM, suggesting
      possible layer compression caused by the tip tapping. An increase in the antibody
      concentration to 10 mg.L(-1) led to increasing surface adsorption. The
      corresponding layer structure was well represented by a three-layer model
      consisting of an inner sublayer of 10 A, a middle sublayer of 30 A, and an outer
      sublayer of 25 A, with the protein volume fractions in each sublayer being 0.22,
      0.42, and 0.10, respectively. The structural transition can be interpreted as a
      twisting and tilting of segments of the adsorbed molecules, driven by an
      electrostatic repulsion between them that increases with the surface packing
      density. Hindrance of antigen access to antibody binding sites, resulting from
      the change in surface packing, can account for the decrease in antigen binding
      capacity (AgBC) with increasing surface density of the antibody that is observed.

PMID- 16800693
TI  - Role of surface coating in ZrO2/Eu3+ nanocrystals.
AB  - The sol-emulsion-gel method is used for the preparation of Eu3+ ion-doped and
      coated ZrO2 nanocrystals. Here, we report the role of surface coating, dopant
      concentration, and temperature of heating in the modification of their crystal
      structure and photoluminescence properties. It is found that the volume fraction
      of the tetragonal phase increases from 28.08 to 91.56% because of surface
      coating. This is a significant modification of the crystal phase in ZrO2
      nanocrystals due to surface coating by Eu2O3. It is found that the
      photoluminescence properties are sensitive to the crystal structure, which is
      again controlled by surface coating, concentration, and heating temperature. It
      is found that the decay time (tau) of Eu-doped ZrO2 nanocrystals increases with
      increasing the concentration of dopant and with increasing the temperature of
      heating because of changes in their crystal phase. The emission intensity of the
      peak at 611-617 nm (5D0 --> 7F2) of the Eu3+ ion-activated ZrO2 nanocrystals
      (doped and coated) is also found to be sensitive to the nanoenvironment. The
      average decay times are 770 and 488 mus for 1100 degrees C-heated 1.0 mol % Eu2O3
      doped and coated ZrO2 nanocrystals, respectively. Our analysis suggests that the
      site symmetry of the ions plays the most important role in the modifications of
      the radiative and nonradiative relaxation mechanisms as a result of the overall
      photoluminescence properties.

PMID- 16800694
TI  - "Sponge" nanoparticle dispersions in aqueous mixtures of diglycerol monooleate,
      glycerol dioleate, and polysorbate 80.
AB  - Lipid nanoparticles of nonlamellar lyotropic phases have a wide solubilizing and
      encapsulating spectrum for a range of substances thanks to their nanostructured
      interior featuring both lipophilic and hydrophilic domains. As a consequence,
      these systems have emerged as promising drug delivery systems in various
      pharmaceutical and diagnostic applications. Here we present the phase behavior
      and dispersion properties of a novel three-component lipid system composed of
      diglycerol monooleate (DGMO), glycerol dioleate (GDO), and polysorbate 80 (P80)
      which shows several advantageous features relating to drug delivery applications
      including: spontaneous dispersion formation with a narrow size distribution and
      tunable particle phase-structure. The obtained phase diagram shows the presence
      of lamellar (L(alpha)), hexagonal (H(2)), and reverse bicontinuous cubic (V(2))
      liquid crystalline phases and an inverse micellar (L(2)) solution. A particularly
      interesting observation is the presence of a phase region where two liquid phases
      coexist, most likely the L(2) and L(3) ("sponge phase"). These two phase
      structures appear also to coexist in the submicron particles formed in the dilute
      water region, where the L(3) element appears to stabilize nanoparticles with
      inner L(2) structure. Increasing the fraction of the dispersing P80 component
      results in the growth of the more water rich L(3) "surface phase" at the expense
      of the size of the inner L(2) core.

PMID- 16800695
TI  - Modulation of the morphology of ZnO nanostructures via aminolytic reaction: from
      nanorods to nanosquamas.
AB  - Various diversified morphology-modulated ZnO nanostructures including nanorods,
      nanotetrahedrons, nanofans, nanodumbbells, and nanosquamas have been successfully
      prepared via an effective aminolytic reaction of zinc carboxylates with
      oleylamine in noncoordinating and coordinating solvents. Their shape- and
      structural defect-dependent optical properties have been investigated as well.
      Highly crystalline defect-free nanotetrahedrons/nanorods have a sharp band-edge
      emission, and highly defective nanodumbbells/nanosquamas show a very broad deep
      trap emission, resulting from the radiative recombination of electrons with holes
      in singly ionized oxygen vacancies.

PMID- 16800696
TI  - Highly luminescent, stable, and water-soluble CdSe/CdS core-shell dendron
      nanocrystals with carboxylate anchoring groups.
AB  - A dendron ligand with two carboxylate anchoring groups at its focal point and
      eight hydroxyl groups as its terminal groups was found to efficiently convert as
      synthesized CdSe/CdS core-shell nanocrystals in toluene to water-soluble dendron
      ligand stabilized nanocrystals (dendron nanocrystals). The resulting dendron
      nanocrystals retained 60% of the photoluminescence value of the original CdSe/CdS
      core-shell nanocrystals in toluene and were significantly brighter than the
      similar dendron nanocrystals with thiolate (deprotonated thiol group) as the
      anchoring group which retained just 10% of the photoluminescence value of the
      original CdSe/CdS core-shell nanocrystals in toluene. The carboxylate-based
      dendron nanocrystals survived UV irradiation in air for at least 13 days, about 9
      times better than the thiolate-based dendron nanocrystals (35 h) and similar to
      that of the thiolate-based dendron-box stabilized CdSe/CdS core-shell
      nanocrystals (box nanocrystals). Upon UV irradiation, the dendron nanocrystals
      became even 2 times brighter than the original CdSe/CdS core-shell nanocrystals
      in toluene, and the UV-brightened PL can retain the brightness for at least
      several months. These stable and bright dendron nanocrystals were soluble in
      various aqueous media, including all common biological buffer solutions tested,
      for at least 1.5 years. In addition to their superior performance, the synthetic
      chemistry of carboxylate dendron ligands and the corresponding dendron
      nanocrystals is relatively simple and with high yield.

PMID- 16800697
TI  - Arrays of covalently bonded single gold nanoparticles on thiolated molecular
      assemblies.
AB  - A simple approach to form arrays of covalently bonded single gold nanoparticles
      (AuNPs) is demonstrated. Asymmetric molecular assemblies composed of two layers
      of rigid aromatic molecules with different structures, arranged in hexagonal
      arrays on a template produced by edge-spreading lithography, are used to guide
      the assembly of AuNPs. Arrays of single AuNPs are achieved by taking advantage of
      the interplay of electrostatic interactions and covalent bonding in conjunction
      with the positional constraint on the template. Schiff base chemistry is
      highlighted in the surface chemical reaction to selectively modify nanoscale
      surface features with high yield.

PMID- 16800698
TI  - Synthesis and aggregation behavior of thermally responsive star polymers.
AB  - To mimic the three-dimensional (3-D) globular architecture resulting from the
      precise positioning of hydrophobic/hydrophilic domains (blocks) of naturally
      occurring proteins, water-soluble linear and star homopolymers of N,N'
      dimethylacrylamide (DMA) were synthesized with prescribed molecular weights via
      reversible addition-fragmentation chain transfer (RAFT) polymerization and
      subsequently used as macro chain transfer agents for block copolymerization with
      N-isopropylacrylamide (NIPAM). For the star block copolymers, the interior block
      consisted of NIPAM while the exterior block was DMA. Since polyNIPAM thermally
      switches from hydrophilic to hydrophobic, the 3-D solution conformations of the
      polymers were studied as a function of temperature using differential scanning
      calorimetry (DSC), static light scattering (SLS), and dynamic light scattering
      (DLS). The polymers were observed to form monodisperse aggregates in an aqueous
      pH 4 buffer solution when heated above the lower critical solution temperature
      (LCST) of polyNIPAM. The temperature at which the polymers aggregated and the
      size of the aggregates were dependent on the NIPAM block length and the core
      architecture. A simple model based on an optimal area per headgroup was used to
      analyze our experimental findings and was useful for predicting the final size
      and molecular weight of the aggregates formed.

PMID- 16800699
TI  - Acceleration of laser-induced formation of gold nanoparticles in a poly(vinyl
      alcohol) film.
AB  - Gold nanoparticles (AuNps) were fabricated in a poly(vinyl alcohol) (PVA) film
      using the photochemically generated benzophenone ketyl radical and PVA radical by
      laser irradiation as a reducing agent. The measurements of the surface plasmon
      band of AuNps indicated that AuNps continued growing in the PVA film for several
      hours or days after the laser irradiation. The formation process of AuNps in the
      PVA film was investigated by using laser flash photolysis and UV-vis absorption
      spectroscopy. Additive doping (formic acid or sodium 2-mercaptoethanesulfonate)
      in the PVA film dramatically accelerated or inhibited the formation rate of the
      AuNps, respectively. The doping of formic acid accelerated the formation rate of
      the AuNps by a factor of 10-20. On the contrary, doping of 2
      mercaptoethanesulfonate inhibited the formation of AuNps. The mechanisms of the
      acceleration and inhibition were investigated by using laser flash photolysis.
      The effects of additives on the formation process of AuNps are discussed.

PMID- 16800700
TI  - Synthesis of tubular gold and silver nanoshells using silica nanowire core
      templates.
AB  - We report the synthesis of tubular gold and silver nanoshells on silica nanowire
      core templates in solution. Silica nanowires were synthesized and characterized
      with optical and NMR methods. Gold nanoparticle seeds (2 to 3 nm) with weak
      repulsive surfactants such as tetrakis-hydroxymethyl-phosphonium chloride (THPC)
      were conjugated to the surface of these nanowires. A regrowth process was
      initiated from these nanoparticles on the surface of the silica nanowires
      dispersed in gold or silver stock solutions in the presence of reducing agents.
      Micrometers-long gold and silver tubular nanoshells (80-150 nm o.d.) were made,
      fully covering the silica nanowires.

PMID- 16800701
TI  - Surfactant and polyelectrolyte gel particles that swell reversibly.
AB  - Mixing of oppositely charged surfactants and polyelectrolytes in aqueous
      solutions can lead to associative phase separation, where the concentrated phase
      is a viscous liquid, gel, or precipitate. In recent years, this phenomenon has
      been exploited to form gel-like particles, ranging from approximately 100 to 4000
      microm in diameter, whose stability depends on equilibrium phase behavior. As the
      sample composition is varied, these particles either remain stable (in a two
      phase mixture) or dissolve over time. Here, we present the formation of
      reversibly swelling gel particles from mixtures of N,N,N-trimethylammonium
      derivatized hydroxyethyl cellulose (JR-400) and sodium dodecyl sulfate (SDS),
      whose swelling is controlled by the ambient solution conditions. The effects of
      cross-linking density and surfactant concentration are investigated by gravimetry
      and confocal microscopy. The resulting particles have a core/shell morphology and
      undergo reversible swelling/collapse transitions which, depending on the cross
      link density, can be either gradual or abrupt with changing SDS concentration.

PMID- 16800702
TI  - Thermosensitive pluronic micelles stabilized by shell cross-linking with gold
      nanoparticles.
AB  - Gold nanoparticles were employed to prepare shell cross-linked Pluronic micelles
      that exhibit a reversibly thermosensitive swelling/shrinking behavior. Two
      terminal hydroxyl groups of Pluronic F127 were thiol-functionalized to form self
      assembling Pluronic micelles in aqueous solution with exposed -SH groups in an
      outer shell layer. The thiol groups present in the outer shell were cross-linked
      by gold nanoparticles synthesized through NaBH4 reduction of gold precursor
      anions. The resultant shell cross-linked gold-Pluronic micelles exhibited a
      temperature-dependent volume transition: their hydrodynamic diameter was changed
      from 157.1 +/- 15.6 nm at 15 degrees C to 53.4 +/- 5.5 nm at 37 degrees C as
      determined by dynamic light scattering. The critical micelle temperature measured
      by a pyrene solubilization technique suggested that the reversible
      swelling/shrinking behavior of the micelles was caused by hydrophobic
      interactions of cross-linked or grafted Pluronic copolymer chains in the micelle
      structure with increasing temperature. Transmission electron microscopy directly
      revealed that the shell cross-linked micelles were indeed produced by gold
      nanoparticles covalently clustered on the surface. These novel self-assembled
      organic/inorganic hybrid micelles would hold great potential for diagnostic and
      therapeutic applications.

PMID- 16800703
TI  - Molecular dynamics simulation of nanoparticle self-assembly at a liquid-liquid
      interface.
AB  - We have used molecular dynamics simulations to investigate the in situ self
      assembly of modified hydrocarbon nanoparticles (mean diameter of 1.2 nm) at a
      water-trichloroethylene (TCE) interface. The nanoparticles were first distributed
      randomly in the water phase. The MD simulation shows the in situ formation of
      nanoparticle clusters and the migration of both single particles and clusters
      from the water phase to the trichloroethylene phase, possibly due to the
      hydrophobic nature of the nanoparticles. Eventually, the single nanoparticles or
      clusters equilibrate at the water-TCE interface, and the surrounding liquid
      molecules pack randomly when in contact with the nanoparticle surfaces. In
      addition, the simulations show that the water-TCE interfacial thickness analyzed
      from density profiles is influenced by the presence of nanoparticles either near
      or in contact with the interface but is independent of the number of
      nanoparticles present. The nanoparticles, water molecules, and TCE molecules all
      exhibit diffusion anisotropy.

PMID- 16800704
TI  - Synthesis of a three-dimensional cubic mesoporous silica monolith employing an
      organic additive through an evaporation-induced self-assembly process.
AB  - We demonstrate a robust approach to the synthesis of a 3D cubic Im3m mesoporous
      silica monolith from SiO2/cetyltrimethylammoniumbromide (CTAB)/1,3,5
      triisopropylbenzene (TIPB) sols having molar compositions of
      1SiO2/0.0017HCl/5.2H2O/10EtOH/0.10CTAB/0.1-0.5TIPB by the evaporation-induced
      self-assembly (EISA) process. The addition of TIPB is aimed at altering the
      micelle geometry to spheroid from rodlike in the gel state; the change in micelle
      geometry leads to the formation of a 3D cage-type cubic mesostructure in the
      monolith. The synthesized materials exhibit BET surface areas of 800-1000 m(2)/g,
      a BJH pore diameter of 2.9-4.3 nm, and a pore volume of 0.7-1.0 cm(3)/g,
      demonstrating ultrahigh porosity of the 3D cubic mesostructure.

PMID- 16800705
TI  - Fibril formation of 1,3:2,4-di(3,4-dimethylbenzylidene) sorbitol in a
      polypropylene melt.
AB  - Binary mixtures of 1,3:2,4-di(3,4-dimethylbenzylidene) sorbitol (DMDBS) within
      the melt of polypropylene (PP) were studied at DMDBS contents of 0.4 and 1.0 wt
      %. DMDBS serves as a nucleating agent in PP crystallization by formation of a
      nanofibrillar network. The kinetics of the DMDBS solidification process within
      the PP melt and the ensuing nanofibrillar structure were studied by in situ small
      angle X-ray scattering (SAXS) analysis combined with imaging by electron
      microscopy. The dynamic lag of the fibrillar structure formation kinetics and its
      temperature dependence indicate a nucleation and growth mechanism, controlled by
      the rate of nucleation. Investigation of the fibrillar structure by electron
      microscopy indicates a complex structure in which long and thin fibrils (less
      than 100 nm in cross-section) are composed of thinner nanofibrils (less than 10
      nm in cross-section).

PMID- 16800706
TI  - A novel method for the fabrication of monodisperse hollow silica spheres.
AB  - In this paper, we report a novel method for the fabrication of small monodisperse
      hollow silica spheres. In this approach, when silica shells were coated on
      polystyrene particles by the sol-gel method, the polystyrene cores were dissolved
      subsequently, even synchronously, in the same medium to form monodisperse hollow
      spheres. Neither additional dissolution nor a calcination process was needed to
      remove the polystyrene cores. Transmission electron microscopy, scanning electron
      microscopy, and porosity measurements were used to characterize the monodisperse
      hollow silica spheres.

PMID- 16800707
TI  - Effects of ultrasmall orifices on the electrogeneration of femtoliter-volume
      aqueous droplets.
AB  - The ability to generate individual picoliter- and femtoliter-volume aqueous
      droplets on demand is useful for encapsulating and chemically manipulating
      discrete chemical and biological samples. This paper characterizes the effects of
      orifice dimensions and material choices on generating such droplets in an
      immiscible oil phase by using single high-voltage pulses with various amplitudes
      and durations. We have examined microfluidic orifices as small as 1.7 microm in
      equivalent radii and found that the electrohydrodynamic jet lengths and the
      subsequent formation of droplets are affected by the axial aspect ratios of the
      orifices (length of an orifice divided by its equivalent radius). As higher
      voltages were used to compensate for the increased capillary pressure and
      hydrodynamic resistance in ultrasmall orifices, we observed secondary jet
      protrusions and droplet formations that were not of classical electrohydrodynamic
      origin. The droplets generated from secondary jets traveled at relatively lower
      velocities as compared to those of electrohydrodynamic origin, and these slow
      individual droplets are potentially more useful for applications in microscale
      chemical reactions.

PMID- 16800708
TI  - Modification of the surface adsorption properties of alumina-supported Pd
      catalysts for the electrocatalytic hydrogenation of phenol.
AB  - The electrocatalytic hydrogenation (ECH) of phenol has been studied using
      palladium supported on gamma-alumina (10% Pd-Al2O3) catalysts. The catalyst
      powders were suspended in aqueous supporting electrolyte solutions containing
      methanol and short-chain aliphatic acids (acetic acid, propionic acid, or butyric
      acid) and were dynamically circulated through a reticulated vitreous carbon
      cathode. The efficiency of the hydrogenation process was measured as a function
      of the total electrolytic charge and was compared for different types of
      supporting electrolyte and for various solvent compositions. Our results show
      that these experimental parameters strongly affect the overall ECH efficiency of
      phenol. The ECH efficiency and yields vary inversely with the quantity of
      methanol present in the electrolytic solutions, whereas the presence of aliphatic
      carboxylic acids increased the ECH efficiency in proportion to the chain length
      of the specific acids employed. In all cases, ECH efficiency was directly
      correlated with the adsorption properties of phenol onto the Pd-alumina catalyst
      in the studied electrolyte solution, as measured independently using dynamic
      adsorption isotherms. It is shown that the alumina surface binds the aliphatic
      acids via the carboxylate terminations and transforms the catalyst into an
      organically functionalized material. Temperature-programmed mass spectrometry
      analysis and diffuse-reflectance infrared spectroscopy measurements confirm that
      the organic acids are stably bound to the alumina surface below 200 degrees C,
      with coverages that are independent of the acid chain length. These reproducibly
      functionalized alumina surfaces control the adsorption/desorption equilibrium of
      the target phenol molecules and allow us to prepare new electrocatalytic
      materials to enhance the efficiency of the ECH process. The in situ grafting of
      specific aliphatic acids on general purpose Pd-alumina catalysts offers a new and
      flexible mechanism to control the ECH process to enhance the selectivity,
      efficiency, and yields according to the properties of the specific target
      molecule.

PMID- 16800709
TI  - Preparation of high catalyst utilization electrodes for polymer electrolyte fuel
      cells.
AB  - We have developed a novel preparation procedure for an electrocatalyst layer with
      high utilization of catalyst for polymer electrolyte fuel cells. A commercial Pt
      catalyst supported on high surface area carbon black (Pt/CB) and Nafion ionomer
      solution was heated in an autoclave at 200 degrees C, followed by quenching to
      form the ink of the mixture. It was found that the cathode prepared with the new
      catalyst ink exhibited very high performance, i.e., high catalyst utilization and
      improved gas diffusivity. The microstructure analysis indicated that the
      autoclave treatment promoted an effective introduction of Nafion ionomer into
      primary pores of Pt/CB agglomerates, in which ca. 90% of Pt catalysts were
      supported. It was clearly observed by scanning transmission electron microscopy
      that Nafion ionomer was distributed more uniformly inside Pt/CB agglomerates,
      compared with those simply mixed with a ball mill in a conventional manner.

PMID- 16800710
TI  - Surface-directed boundary flow in microfluidic channels.
AB  - Channel geometry combined with surface chemistry enables a stable liquid boundary
      flow to be attained along the surfaces of a 12 microm diameter hydrophilic glass
      fiber in a closed semi-elliptical channel. Surface free energies and triangular
      corners formed by PDMS/glass fiber or OTS/glass fiber surfaces are shown to be
      responsible for the experimentally observed wetting phenomena and formation of
      liquid boundary layers that are 20-50 microm wide and 12 microm high. Viewing
      this stream through a 20 microm slit results in a virtual optical window with a 5
      pL liquid volume suitable for cell counting and pathogen detection. The geometry
      that leads to the boundary layer is a closed channel that forms triangular
      corners where glass fiber and the OTS coated glass slide or PDMS touch. The
      contact angles and surfaces direct positioning of the fluid next to the fiber.
      Preferential wetting of corner regions initiates the boundary flow, while the
      elliptical cross-section of the channel stabilizes the microfluidic flow. The
      Young-Laplace equation, solved using fluid dynamic simulation software, shows
      contact angles that exceed 105 degrees will direct the aqueous fluid to a
      boundary layer next to a hydrophilic fiber with a contact angle of 5 degrees. We
      believe this is the first time that an explanation has been offered for the case
      of a boundary layer formation in a closed channel directed by a triangular
      geometry with two hydrophobic wetting edges adjacent to a hydrophilic surface.

PMID- 16800711
TI  - Viscosimeter on a microfluidic chip.
AB  - In this work, a viscosimeter implemented on a microfluidic chip is presented. The
      physical principle of this system is to use laminar parallel flows in a
      microfluidic channel. The fluid to be studied flows side by side with a reference
      fluid of known viscosity. By using optical microscopy, the shape of the interface
      between both fluids can be determined. Knowing the flow rates of the two liquids
      and the geometrical features of the channel, the mean shear rate sustained by the
      fluid and its viscosity can thus be computed. Accurate and precise measurements
      of the viscosity as a function of the shear rate can be made using less than 300
      microL of fluid. Several complex fluids are tested with viscosities ranging from
      10(-)(3) to 70 Pa.s.

PMID- 16800712
TI  - Designing highly specific biosensing surfaces using aptamer monolayers on gold.
AB  - To build highly specific surfaces using aptamer affinity reagents, the effects of
      linker and coadsorbents were investigated for maximizing target binding and
      specificity for aptamer-based self-assembled monolayers (SAMs) supported on gold.
      An aptamer that binds the protein thrombin was utilized as a model system to
      compare different mixed monolayer systems toward maximizing binding and
      selectivity to the immobilized aptamer. Important factors used to optimize
      binding characteristics of thrombin to the aptamer-based monolayer films include
      changes in design elements of the linker and different coadsorbent thiols.
      Binding events measured by surface plasmon resonance (SPR) and ellipsometry
      showed that the binding performance of the aptamer SAMs depends principally on
      the linker and to a lesser extent on the coadsorbent. SAMs formed with HS-(CH2)6
      OP(O)2O-(CH2CH2O)6-TTTTT-aptamer exhibited a 4-fold increase in binding capacity
      versus SAMs made using HS-(CH2)6-TTTTT-aptamer. Furthermore, SAMs made using HS
      (CH2)6-OP(O)2O-(CH2CH2O)6-TTTTT-aptamer showed nearly complete specificity for
      thrombin versus bovine serum albumin (BSA, less than 2% bound), while a SAM
      incorporating a random DNA fragment (HS-(CH2)6-OP(O)2O-(CH2CH2O)6-TTTTT-RANDOM)
      showed little binding of thrombin. Irrespective of the aptamer-linker system, use
      of HS-(CH2)11(OCH2CH2)3OH, referred to as EG(3), as a coadsorbent enhanced
      binding of thrombin by approximately 2.5-fold compared to that of HS-(CH2)6-OH
      (mercaptohexanol, MCH).

PMID- 16800713
TI  - Influence of humidity on the fabrication of high-quality colloidal crystals via a
      capillary-enhanced process.
AB  - Three-dimensional colloidal crystals have attracted a great deal of attention
      because of their potential use in photonic crystal, sensors, and other
      applications, but the bottlenecks in fabricating colloidal crystals include
      longer processing time and the lack of large-area ordered samples. A proposed
      capillary-enhanced method, which is a novel, efficient process for fabricating
      high-quality colloidal crystals in 24 h, is reported. It is necessary for
      increasing the processing rate by elevating the evaporation temperature but
      commonly resulted in the deposition of less-ordered crystals. However, high
      quality colloidal crystals can be obtained in a controlled high-humidity system,
      resulting from the existence of secondary capillary forces present in high
      ambient humidity. Furthermore, the effect of secondary capillary forces will be
      confirmed, and it will increase with increasing humidity levels according to the
      semiquantitative analysis view of the surface thermodynamic behavior of small
      particles, including the modified Kelvin and Young-Laplace equations. Therefore,
      it can fine tune the relative position of the neighboring particles in the
      microarray and efficiently decrease the number of defects, resulting in the
      formation of perfect colloidal crystals with the assistance of enhanced secondary
      capillary forces.

PMID- 16800714
TI  - Are there differential symptom profiles that improve in response to different
      pharmacological treatments of premenstrual syndrome/premenstrual dysphoric
      disorder?
AB  - Current evidence suggests that the accepted treatments for premenstrual syndrome
      (PMS)/premenstrual dysphoric disorder (PMDD) have similar overall efficacy. While
      these treatments are more effective than placebo, response rates associated with
      them are far from satisfactory (<60%), such that, irrespective of treatment
      modality, there remain a significant number of women who are unresponsive to
      current conventional pharmacological therapy. The available data on response
      rates of specific types of premenstrual symptoms to, or symptom profiles that are
      most amenable to, each treatment modality are limited and not well defined
      because most studies were not designed to assess specific symptom profiles. Those
      studies that have attempted to evaluate which symptom profiles respond to
      specific therapies have revealed variations within the individual modalities, as
      well as between the different modalities. It appears that suppression of
      ovulation ameliorates a broad range of behavioural as well as physical
      premenstrual symptoms. SSRIs are most effective for irritability and anxiety
      symptoms, with lesser efficacy for 'atypical' premenstrual symptoms. GABAergic
      compounds are most efficacious for anxiety and anxious/depressive symptoms, while
      dopamine agonists, particularly bromocriptine, are perhaps most efficacious for
      mastalgia. Overall treatment response rates may improve if treatments are
      targeted at well-defined subgroups of patients. Re-analysis of available datasets
      from randomised clinical trials may shed more light on the notion that targeting
      women with specific premenstrual symptom profiles for specific treatment
      modalities would improve response rates beyond the current ceiling of
      approximately 60%. Such information would also improve understanding of the
      putative pathophysiological mechanisms underlying PMS and PMDD, and may point to
      a more specific diagnosis of these conditions.

PMID- 16800715
TI  - Pharmacological aspects of the treatment of conduct disorder in children and
      adolescents.
AB  - In recent years, the rates of psychosocial disorders in children and adolescents
      have increased, with behavioural manifestations of conduct disorder being one of
      the most common reasons for referrals to community psychiatrists. Childhood
      conduct problems are associated with a variety of psychiatric disorders in adult
      life that extend beyond antisocial behaviour. An increased awareness of the costs
      of conduct disorder to individuals, families and society has led to advancements
      in the pharmacological and nonpharmacological therapeutic modalities for this
      disorder. Despite this, patients with conduct disorder are difficult to treat as
      the patterns of maladaptive behaviours they exhibit are diverse and can vary as a
      function of age and sex. A multidisciplinary approach to the treatment of conduct
      disorder, which includes behavioural parent training, interpersonal skills
      training, family therapy and the use of psychotropic agents targeted at a
      particular cluster of symptoms, can increase the overall effectiveness of each of
      the applied interventions. Aggression, hyperactivity, impulsivity and mood
      symptoms are the most sensitive proximal targets. Evidence suggests that
      antipsychotics, antidepressants, mood stabilisers, antiepileptic drugs,
      stimulants and adrenergic drugs can be well tolerated and effective therapeutic
      options for individuals with conduct disorder and comorbid psychiatric
      conditions. However, the most successful therapeutic outcomes are likely to be
      achieved by combining the current advances in psychopharmacology with behavioural
      and psychosocial interventions, aimed at modifying the excessive patterns of
      maladaptive behaviours observed in conduct disorder.

PMID- 16800718
TI  - Retigabine: in partial seizures.
AB  - Retigabine has anticonvulsant properties that appear to be primarily mediated by
      opening neuronal voltage-gated potassium channels. This action has been shown in
      neuronal KCNQ2/3 and KCNQ3/5 potassium channels. In addition to this unique
      action, retigabine also potentiates GABA-evoked currents in cortical neurons at
      high concentrations. When used as adjunctive therapy in patients with partial
      seizures, retigabine 600-1200 mg/day (200-400 mg three times daily) was
      associated with significant linear dose-dependent reductions in monthly seizure
      frequency compared with placebo in a large 16-week randomised phase II trial.
      Median monthly seizure frequency decreased from baseline by up to 35% among
      patients in the retigabine treatment arms compared with 13% in the placebo group.
      Retigabine 1200 mg/day was also significantly more effective than retigabine 600
      mg/day. Responder rates, defined as the proportion of patients with > or = 50%
      reduction in seizure frequency, were significantly higher among patients in the
      retigabine 900 and 1200 mg/day groups than in those who received placebo. CNS
      related adverse events were the most commonly reported treatment-emergent adverse
      events associated with retigabine in clinical trials. Across all three retigabine
      groups in the large phase II trial, somnolence (20.3%), dizziness (14.6%),
      confusion (12.3%) and speech disorder (11.3%) were the most frequent CNS-related
      adverse events.

PMID- 16800717
TI  - Economics of atypical antipsychotics in bipolar disorder: a review of the
      literature.
AB  - Economic evaluations are increasingly being used by policy makers to evaluate the
      relative costs and benefits of healthcare interventions. These analyses provide
      economic and clinical evidence to decision makers seeking to make recommendations
      on treatment alternatives for patients. This article describes the economic
      evidence on the atypical antipsychotics currently approved for the treatment of
      bipolar disorder. This area remains under-researched. A literature search
      identified only six relevant studies of atypical antipsychotics in bipolar
      disorder: two retrospective database analyses, three economic analyses alongside
      clinical trials and one cost-effectiveness analysis. Based on the limited
      available studies, there appears to be no significant difference in healthcare
      resource use between olanzapine, quetiapine, risperidone and valproate semisodium
      (divalproex sodium; an antiepileptic drug and a standard treatment for mania
      associated with bipolar disorder). While a cost-effectiveness study for the UK
      found haloperidol (a conventional antipsychotic) to be more cost effective than
      atypical antipsychotics, these results must be considered with caution because of
      the non-inclusion of adverse effects in the model. No economic data are available
      for aripiprazole, clozapine or ziprasidone in bipolar disorder. Until more
      economic evidence becomes available, the economic implications of atypical
      antipsychotic treatment in patients with bipolar disorder are unlikely to
      significantly impact on prescribing and treatment patterns. Future economic
      studies evaluating atypical antipsychotics in bipolar disorder should address the
      issue of long-term costs and effectiveness to reflect the chronic nature of the
      disease, the variety of health states that patients may experience and the range
      of treatments they may receive. A better understanding of the complex interplay
      between effectiveness, safety, quality of life, adherence and resource use should
      ultimately contribute to improving the treatment of bipolar disorder.

PMID- 16800716
TI  - Sleep disturbances in patients with post-traumatic stress disorder: epidemiology,
      impact and approaches to management.
AB  - Subjective reports of sleep disturbance indicate that 70-91% of patients with
      post-traumatic stress disorder (PTSD) have difficulty falling or staying asleep.
      Nightmares are reported by 19-71% of patients, depending on the severity of their
      PTSD and their exposure to physical aggression. Objective measures of sleep
      disturbance are inconsistent, with some studies that used these measures
      indicating poor sleep and others finding no differences compared with non-PTSD
      controls. Future research in this area may benefit from examining measures of
      instability in the microstructure of sleep. Additionally, recent findings suggest
      that sleep disordered breathing (SDB) and sleep movement disorders are more
      common in patients with PTSD than in the general population and that these
      disorders may contribute to the brief awakenings, insomnia and daytime fatigue in
      patients with PTSD. Overall, sleep problems have an impact on the development and
      symptom severity of PTSD and on the quality of life and functioning of patients.
      In terms of treatments, SSRIs are commonly used to treat PTSD, and evidence
      suggests that they have a small but significant positive effect on sleep
      disruption. Studies of serotonin-potentiating non-SSRIs suggest that nefazodone
      and trazodone lead to significant reductions in insomnia and nightmares, whereas
      cyproheptadine may exacerbate sleep problems in patients with PTSD. Prazosin, a
      centrally acting alpha1-adrenoceptor antagonist, has led to large reductions in
      nightmares and insomnia in small studies of patients with PTSD. Augmentation of
      SSRIs with olanzapine, an atypical antipsychotic, may be effective for treatment
      resistant nightmares and insomnia, although adverse effects can be significant.
      Additional medications, including zolpidem, buspirone, gabapentin and
      mirtazapine, have been found to improve sleep in patients with PTSD. Large
      randomised, placebo-controlled trials are needed to confirm the above findings.
      In contrast, evidence suggests that benzodiazepines, TCAs and MAOIs are not
      useful for the treatment of PTSD-related sleep disorders, and their adverse
      effect profiles make further studies unlikely. Cognitive behavioural
      interventions for sleep disruption in patients with PTSD include strategies
      targeting insomnia and imagery rehearsal therapy (IRT) for nightmares. One large
      randomised controlled trial of group IRT demonstrated significant reductions in
      nightmares and insomnia. Similarly, uncontrolled studies combining IRT and
      insomnia strategies have demonstrated good outcomes. Uncontrolled studies of
      continuous positive airway pressure for SDB in patients with PTSD show that this
      treatment led to significant decreases in nightmares, insomnia and PTSD symptoms.
      Controlled studies are needed to confirm these promising findings.

PMID- 16800723
TI  - Proceedings of the 1st International Symposium on Kallikreins, Lausanne,
      Switzerland, September 1-3 , 2005.

PMID- 16800722
TI  - Mechanism of G-protein activation by rhodopsin.
AB  - Rhodopsin is a member of the family of G-protein-coupled receptors (GPCRs), and
      is an excellent molecular switch for converting light signals into electrical
      response of the rod photoreceptor cells. Light initiates cis-trans isomerization
      of the retinal chromophore of rhodopsin and leads to the formation of several
      thermolabile intermediates during the bleaching process. Recent investigations
      have identified spectrally distinguishable two intermediate states that can
      interact with the retinal G-protein, transducin, and have elucidated the
      functional sharing of these intermediates. The initial contact with GDP-bound G
      protein occurs in the meta-Ib intermediate state, which has a protonated Schiff
      base as its chromophore. The meta-Ib intermediate in the complex with the G
      protein converts to the meta-II intermediate with releasing GDP from the alpha
      subunit of the G protein. Meta-II has a de-protonated Schiff base chromophore and
      induces binding of GTP to the alpha-subunit of the G-protein. Thus, the GDP-GTP
      exchange reaction, namely G-protein activation, by rhodopsin proceeds through at
      least two steps, with conformational changes in both rhodopsin and the G-protein.

PMID- 16800721
TI  - Predicting survival within the lung cancer histopathological hierarchy using a
      multi-scale genomic model of development.
AB  - BACKGROUND: The histopathologic heterogeneity of lung cancer remains a
      significant confounding factor in its diagnosis and prognosis-spurring numerous
      recent efforts to find a molecular classification of the disease that has
      clinical relevance. METHODS AND FINDINGS: Molecular profiles of tumors from 186
      patients representing four different lung cancer subtypes (and 17 normal lung
      tissue samples) were compared with a mouse lung development model using principal
      component analysis in both temporal and genomic domains. An algorithm for the
      classification of lung cancers using a multi-scale developmental framework was
      developed. Kaplan-Meier survival analysis was conducted for lung adenocarcinoma
      patient subgroups identified via their developmental association. We found multi
      scale genomic similarities between four human lung cancer subtypes and the
      developing mouse lung that are prognostically meaningful. Significant association
      was observed between the localization of human lung cancer cases along the
      principal mouse lung development trajectory and the corresponding patient
      survival rate at three distinct levels of classical histopathologic resolution:
      among different lung cancer subtypes, among patients within the adenocarcinoma
      subtype, and within the stage I adenocarcinoma subclass. The earlier the genomic
      association between a human tumor profile and the mouse lung development
      sequence, the poorer the patient's prognosis. Furthermore, decomposing this
      principal lung development trajectory identified a gene set that was
      significantly enriched for pyrimidine metabolism and cell-adhesion functions
      specific to lung development and oncogenesis. CONCLUSIONS: From a multi-scale
      disease modeling perspective, the molecular dynamics of murine lung development
      provide an effective framework that is not only data driven but also informed by
      the biology of development for elucidating the mechanisms of human lung cancer
      biology and its clinical outcome.

PMID- 16800724
TI  - A comprehensive nomenclature for serine proteases with homology to tissue
      kallikreins.
AB  - The human kallikrein locus on chromosome 19q13.3-13.4 contains kallikrein 1--the
      tissue kallikrein--and 14 related serine proteases. Recent investigations into
      their function and evolution have indicated that the present nomenclature for
      these proteins is inadequate or insufficient. Here we present a new nomenclature
      in which proteins without proven kininogenase activity are denoted kallikrein
      related peptidase. Names are also given to the unique rodent proteins that are
      closely related to kallikrein 1.

PMID- 16800725
TI  - The kallikrein world: an update on the human tissue kallikreins.
AB  - Human tissue kallikreins (hKs) are attracting increased attention owing to their
      association with various forms of cancer and other diseases. Human tissue
      kallikrein genes represent the largest contiguous group of proteases within the
      human genome. There are many areas of kallikrein research that need to be further
      explored, including their tissue expression patterns, their regulation,
      identification of specific substrates, their participation in proteolytic
      cascades, and their clinical applicability as cancer biomarkers and therapeutic
      targets. In this review, we briefly describe the current status of kallikrein
      research and identify future avenues that will enhance our understanding of their
      function and involvement in human diseases.

PMID- 16800726
TI  - Cellular distribution of human tissue kallikreins: immunohistochemical
      localization.
AB  - We have studied the immunohistochemical expression (IE) of eight non-tissue
      specific human kallikreins (hKs) (hK5, 6, 7, 10, 11, 12, 13, and 14) in different
      normal tissues. The IE was always cytoplasmic, showing a characteristic pattern
      in some tissues. Comparison of the IE of all hKs studied in the different tissues
      revealed no major differences, suggesting that they share a common mode of
      regulation. Furthermore, hKs were immunohistochemically revealed in a variety of
      tissues, indicating that no protein is tissue-specific (except for hK2 and hK3,
      which have tissue-restricted expression). In general, our results correspond well
      with data from RT-PCR and ELISA assays. Glandular epithelia constitute the main
      kallikrein IE sites, and the staining in their secretions confirms that these
      proteases are secreted. A variety of other tissues express the proteins as well.
      We have also immunohistochemically evaluated all the above hKs in several
      malignant tissues. Tumors arising from tissues expressing kallikreins tested
      positive. Corresponding to the IE in normal glandular tissues, most hKs were
      expressed in adenocarcinomas. The prognostic value of several hKs was studied in
      series of prostate, renal cell, colon and urothelial carcinomas.

PMID- 16800727
TI  - The tissue kallikrein-kinin system protects against cardiovascular and renal
      diseases and ischemic stroke independently of blood pressure reduction.
AB  - Tissue kallikrein (hK1) cleaves low-molecular-weight kininogen to produce kinin
      peptide, which binds to kinin receptors and triggers a wide spectrum of
      biological effects. Tissue kallikrein levels are reduced in humans and in animal
      models with hypertension, cardiovascular and renal diseases. Transgenic mice or
      rats over-expressing human tissue kallikrein or kinin B2 receptor are permanently
      hypotensive, and somatic kallikrein gene delivery reduces blood pressure in
      several hypertensive rat models. Moreover, kallikrein gene delivery or kallikrein
      protein infusion can directly improve cardiac, renal and neurological function
      without blood pressure reduction. Kallikrein has pleiotropic effects in
      inhibiting apoptosis, inflammation, proliferation, hypertrophy and fibrosis, and
      promoting angiogenesis and neurogenesis in different experimental animal models.
      Kallikrein's effects can be blocked by kinin B2 receptor antagonists.
      Mechanistically, tissue kallikrein/kinin leads to increased nitric oxide levels
      and Akt activation, and reduced reactive oxygen species formation, TGF-beta1
      expression, MAPK and nuclear factor-kappaB activation. Our studies indicate that
      tissue kallikrein, through the kinin B2 receptor and nitric oxide formation, can
      protect against oxidative damage in cardiovascular and renal diseases and
      ischemic stroke. These novel findings suggest that kallikrein/kinin may serve as
      new drug targets for the prevention and treatment of heart failure, renal disease
      and stroke in humans.

PMID- 16800728
TI  - Proteinase-mediated cell signalling: targeting proteinase-activated receptors
      (PARs) by kallikreins and more.
AB  - Serine proteinases, like trypsin, can play a hormone-like role by triggering
      signal transduction pathways in target cells. In many respects these hormone-like
      actions of proteinases can now be understood in terms of the pharmacodynamics of
      the G protein-coupled 'receptor' responsible for the cellular actions of thrombin
      (proteinase-activated receptor-1, or PAR1). PAR1, like the other three members of
      this receptor family (PAR2, PAR3 and PAR4), has a unique mechanism of activation
      involving the proteolytic unmasking of an N-terminally tethered sequence that can
      activate the receptor. The selective activation of each PAR by short synthetic
      peptides representing these sequences has demonstrated that PAR1, PAR2 and PAR4
      play important roles in regulating physiological responses ranging from
      vasoregulation and cell growth to inflammation and nociception. We hypothesise
      that the tissue kallikreins may regulate signal transduction via the PARs.
      Although PARs can account for many of their biological actions, kallikreins may
      also cause effects by mechanisms not involving the PARs. For instance, trypsin
      activates the insulin receptor and thrombin can act via a mechanism involving its
      non-catalytic domains. Based on the data we summarise, we propose that the
      kallikreins, like thrombin and trypsin, must now be considered as important
      'hormonal' regulators of tissue function.

PMID- 16800729
TI  - Recombinant kallikrein expression: site-specific integration for hK6 production
      in human cells.
AB  - Kallikreins have been implicated in carcinogenesis and are promising biomarkers
      for the diagnosis and follow-up of various cancers. To evaluate the functions and
      clinical interest of kallikreins, it is important to be able to produce them as
      recombinant proteins. Here we summarize the various strategies used to produce
      kallikreins, emphasizing their advantages and limitations. We also describe an
      approach to achieve high-level production of kallikreins, such as hK6, with
      correct folding and activity, combining an expression system with targeted
      transgene integration and an efficient cultivation device to increase yield, the
      CELLine bioreactor. This novel method for recombinant kallikrein production will
      be useful to study their bio-pathological functions and to develop anti-bodies.

PMID- 16800730
TI  - Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in
      hormone-related cancers: do they have a function?
AB  - The kallikrein-related peptidase (KLK) gene family of 15 serine proteases encodes
      many proteins, including prostate specific antigen (PSA or KLK3), that are well
      described and/or are potential biomarkers for hormone-related cancers. Variant
      mRNA transcripts produced by alternative splicing, polyadenylation or AUG sites,
      or intron retention have been found for each of the KLK genes. The predicted
      protein for many of these alternative transcripts is different from that of the
      classical kallikrein-related peptidases and would not be an active serine
      protease. The majority of these novel protein isoforms have not been studied in
      vivo. The possible function(s) of the variant transcripts/protein isoforms and
      potential roles that they may play in hormone-related cancers are still unknown
      and are the focus of this short review.

PMID- 16800731
TI  - The role of kallikrein-related peptidases in prostate cancer: potential
      involvement in an epithelial to mesenchymal transition.
AB  - Several members of the kallikrein-related peptidase family of serine proteases
      have proteolytic activities that may affect cancer progression; however, the in
      vivo significance of these activities remains uncertain. We have demonstrated
      that expression of PSA or KLK4, but not KLK2, in PC-3 prostate cancer cells
      changed the cellular morphology from epithelial to spindle-shaped, markedly
      reduced E-cadherin expression, increased vimentin expression and increased
      cellular migration. These changes are indicative of an epithelial to mesenchymal
      transition (EMT), a process important in embryonic development and cancer
      progression. The potential novel role of kallikrein-related peptidases in this
      process is the focus of this brief review.

PMID- 16800733
TI  - Activation and enzymatic characterization of recombinant human kallikrein 8.
AB  - Human kallikrein 8 (hK8), whose gene was originally cloned as the human ortholog
      of a mouse brain protease, is known to be associated with diseases such as
      ovarian cancer and Alzheimer's disease. Recombinant human pro-kallikrein 8 was
      activated with lysyl endopeptidase-conjugated beads. Amino-terminal sequencing of
      the activated enzyme demonstrated the cleavage of a 9-aa propeptide from the pro
      enzyme. The substrate specificity of activated hK8 was characterized using
      synthetic fluorescent substrates. hK8 showed trypsin-like specificity, as
      predicted from sequence analysis and enzymatic characterization of the mouse
      ortholog. All synthetic substrates tested containing either arginine or lysine at
      P1 position were cleaved by hK8. The highest kcat/Km value of 20x10(3)M-1 s-1 was
      observed with Boc-Val-Pro-Arg-7-amido-4-methylcoumarin. The activity of hK8 was
      inhibited by antipain, chymostatin, and leupeptin. The concentration for 50%
      inhibition by the best inhibitor, antipain, was 0.46 microM. The effect of
      different metal ions on the enzyme activity was analyzed. Whereas Na+ had no
      effect on hK8 activity, Ni2+ and Zn2+ decreased the activity and Ca2+, Mg2+, and
      K+ had a stimulatory effect. Ca2+ was the best activator, with an optimal
      concentration of approximately 10 microM.

PMID- 16800732
TI  - Human kallikrein 10, a predictive marker for breast cancer.
AB  - Our laboratory is involved in identifying genes that can be used as early
      diagnostic or prognostic markers in breast cancer. We previously identified a
      gene (NES1) that is expressed in normal but not in transformed mammary epithelial
      cells (MECs). NES1 is located on chromosome 19q13.4 within the kallikrein locus
      and thus was designated as human kallikrein 10 (hK10), although we have been
      unable to detect any protease activity. Importantly, hK10 expression is decreased
      in a majority of breast cancer cell lines. Transfection of hK10 into hK10
      negative breast cancer cells reduces the tumorigenicity. Using methylation
      specific PCR and subsequent sequencing, we demonstrate a strong correlation
      between hypermethylation of hK10 and loss of mRNA expression. Further analysis
      showed that essentially 100% of normal breast specimens had hK10 expression,
      whereas 46% of ductal carcinoma in situ (DCIS) and the majority of infiltrating
      ductal carcinoma (IDC) samples lacked the hK10 mRNA. Importantly, hK10-negative
      DCIS diagnosed at the time of biopsy were subsequently diagnosed as IDC at the
      time of definitive surgery. It has been shown that hK10 protein expression is
      regulated by steroids. In addition to breast cancers, hK10 is downregulated in
      cervical cancer, prostate cancer and acute lymphocytic leukemia, whereas it is
      upregulated in ovarian cancers. These results point to the paradoxical role of
      hK10 in human cancers and underscore the importance of further studies of this
      kallikrein.

PMID- 16800734
TI  - Human tissue kallikrein 9: production of recombinant proteins and specific
      antibodies.
AB  - Human tissue kallikreins (genes, KLKs; proteins, hKs) are a subgroup of
      hormonally regulated serine proteases. Two tissue kallikreins, namely hK2 and hK3
      (prostate-specific antigen, PSA), are currently used as serological biomarkers of
      prostate cancer. Human tissue kallikrein 9 (KLK9) is a newly identified member of
      the tissue kallikrein gene family. Recent reports have indicated that KLK9 mRNA
      is differentially expressed in ovarian and breast cancer and has prognostic
      value. Here, we report the production of recombinant hK9 (classic form) using
      prokaryotic and mammalian cells and the generation of polyclonal antibodies.
      Total testis tissue mRNA was reverse-transcribed to cDNA, amplified, cloned into
      a pET/200 TOPO plasmid vector, and transformed into E. coli cells. hK9 was
      purified and used as an immunogen to generate polyclonal antibodies. Full-length
      KLK9 cDNA was also cloned in the vector pcDNA3.1 and was expressed in CHO cells.
      The identity of hK9 was confirmed by mass spectrometry. hK9 rabbit antiserum
      displayed no cross-reactivity with other tissue kallikreins and could
      specifically recognize E. coli- and CHO-derived hK9 on Western blots. hK9 was
      mainly detected in testis and seminal vesicles by Western blotting. The reagents
      generated here will help to define the physiological role of this tissue
      kallikrein and its involvement in human disease.

PMID- 16800735
TI  - The human kallikrein 10 promoter contains a functional retinoid response element.
AB  - Human kallikrein 10 (hK10) protein is expressed in normal breast but is
      significantly downregulated in a majority of invasive breast cancers. Thus,
      understanding how hK10 expression is regulated is of substantial significance. In
      this study, we analyzed the promoter region of hK10 using a website software
      (TRANSFAC 3.0), which predicted three possible retinoic acid response elements
      (RAREs), RARE1 at -1041 (TGACCTCGTGATCC), RARE2 at -859 (TGACCTCCTATGA) and RARE3
      at -765 (TGACCTCCTGTGA), each with a half-site of a canonical sequence (TGACCT;
      reverse complement AGGTCA). Using electrophoretic mobility shift assays and
      nucleotide competition analysis, as well as chromatin immunoprecipitation of the
      native hK10 promoter, we demonstrated specific binding of RXR only to RARE1. The
      functional importance of RARE in the hK10 promoter was demonstrated by retinoid
      induction of hk10 promoter-reporters; furthermore, mutation of RARE1 but not of
      RARE2 or RARE3 abolished the induction of the reporter. Finally, we demonstrated
      the induction of hK10 mRNA and protein expression upon retinoid treatment of
      cells. In view of the correlation of the downregulation of hK10 mRNA and protein
      with breast cancer progression, these findings suggest a potential approach to
      restore hK10 expression in cancer patients.

PMID- 16800736
TI  - Human kallikrein 4: enzymatic activity, inhibition, and degradation of
      extracellular matrix proteins.
AB  - Human kallikrein 4 (hK4) is a member of the expanded family of human kallikreins,
      a group of 15 secreted proteases. While this protein has been associated with
      ovarian and prostate cancer prognosis, only limited functional information
      exists. Therefore, we have undertaken an investigation of its enzymatic
      properties regarding substrate preference, degradation of extracellular matrix
      proteins, and its inhibition by various inhibitors. We successfully expressed and
      purified active recombinant hK4 from supernatants of the Pichia pastoris
      expression system. This enzyme seems to cleave more efficiently after Arg
      compared to Lys at the P1 position and exhibits modest specificity for amino
      acids at positions P2 and P3. hK4 forms complexes with alpha1-antitrypsin, alpha2
      antiplasmin and alpha2-macroglobulin. The protease mediates limited degradation
      of extracellular matrix proteins such as collagen I and IV, and more efficient
      degradation of the alpha-chain of fibrinogen. The cleavage of extracellular
      matrix proteins by hK4 suggests that this enzyme may play a role in tissue
      remodeling and cancer metastasis.

PMID- 16800737
TI  - Kallikrein-related peptidase 14 may be a major contributor to trypsin-like
      proteolytic activity in human stratum corneum.
AB  - We have previously presented evidence that two human kallikrein-related
      peptidases, KLK5 (hK5, stratum corneum tryptic enzyme, SCTE) and KLK7 (hK7,
      stratum corneum chymotryptic enzyme, SCCE), which are abundant in the stratum
      corneum, may be involved in desquamation. Since we had noted that not all trypsin
      like activity in the plantar stratum corneum could be ascribed to KLK5, we set
      out to identify other skin proteases with similar primary substrate specificity.
      Here we describe purification of a protease identified as KLK14 from plantar
      stratum corneum, and show that this enzyme may be responsible for as much as 50%
      of the total trypsin-like activity in this tissue, measured as activity towards a
      chromogenic substrate cleaved by a wide variety of enzymes with trypsin-like
      specificity. This was in spite of very low levels of KLK14 protein compared to
      KLK5 and KLK7. KLK14 could be detected by immunoblotting in normal superficial
      stratum corneum of all individuals examined. The majority of KLK14 in the plantar
      stratum corneum is present in its catalytically active form. KLK14 could be
      immunohistochemically detected in sweat ducts, preferentially in the
      intraepidermal parts (the acrosyringium), and in sweat glands. The role played by
      this very efficient protease under normal and disease conditions in the skin
      remains to be elucidated.

PMID- 16800738
TI  - A sensitive proximity ligation assay for active PSA.
AB  - Prostate-specific antigen (PSA) is a widely used marker for prostate cancer. The
      utility of PSA tests is limited by their inability to differentiate prostate
      cancer from non-malignant conditions such as benign prostatic hyperplasia and
      prostatitis. In circulation, PSA occurs in various complexed and free forms, and
      specific determination of some of these can be used to improve the diagnostic
      accuracy of PSA tests. We have previously identified peptides that specifically
      bind to enzymatically active PSA and using such a peptide we have developed an
      immunopeptidometric assay for this form of PSA. However, the sensitivity of that
      assay is too low to measure active PSA at clinically important levels. Recently a
      novel sensitive immunoassay for analysis of proteins, termed the proximity
      ligation assay, has been established. Here we describe a sensitive implementation
      of the proximity ligation assay, which utilizes a PSA-binding peptide and
      antibody as probes to detect active PSA. The assay has a sensitivity of 0.07
      microg/l, which is approximately ten-fold lower than that of our previous assay.
      It does not cross-react with inactive proPSA or the highly similar kallikrein
      hK2. Our results show that a highly sensitive immunopeptidometric assay can be
      developed using proximity ligation. This principle should facilitate
      establishment of specific assays for active forms of other proteases.

PMID- 16800739
TI  - Multiple mechanisms underlie the aberrant expression of the human kallikrein 6
      gene in breast cancer.
AB  - Human kallikrein 6 (KLK6) was identified based on its transient upregulation in a
      primary breast tumor and its subsequent silencing in a metastatic tumor from the
      same patient. The molecular mechanism(s) underlying the deregulated expression of
      KLK6 during cancer progression are currently unknown. Here, we provide evidence
      that aberrant expression of KLK6 is regulated at the level of transcription by
      multiple cooperating mechanisms. KLK6 can be reactivated in non-expressing breast
      cancer cells by treatment with 5-aza-2'-deoxycytidine (5-aza-dC), a compound
      causing DNA demethylation. Trichostatin A (TSA), an inhibitor of histone
      deacetylases, resulted in moderate induction of KLK6 only in MDA-MB-231 cells.
      However, combined 5-aza-dC/TSA treatment resulted in synergistic activation of
      KLK6. We show that KLK6 inactivation is associated with hypermethylation of
      specific CpG dinucleotides located in the KLK6 proximal promoter and
      overexpression with complete demethylation. These results indicate a causal role
      of DNA methylation and chromatin structure in cancer-associated loss of KLK6
      expression. In some breast cancer cell lines, KLK6 expression could be restored
      by the vitamin D3 analog EB1089. Our data indicate that transcriptional
      deregulation of KLK6 in cancer cells during breast cancer progression is complex
      and certainly not uniform in different tumors, involving epigenetic mechanisms as
      well as pathways regulated by nuclear receptors. This allows for the
      pharmacological modulation of KLK6 with potential therapeutic implications.

PMID- 16800740
TI  - Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous
      and non-cancerous lung tissues.
AB  - Only one transcript for KLK10 was identified by RT-PCR in lung tissue, whereas
      KLK11 expressed at least four alternative transcripts. Quantitative analysis of
      KLK10 and KLK11 expression levels was assessed by real-time PCR, in a cohort of
      47 patients with non-small-cell lung cancer (NSCLC). Expression levels of these
      genes were widely distributed in the population studied. Multivariate analysis
      revealed a correlation between KLK10 over-expression and the squamous cell
      carcinoma histotype (p=0.034). There was no correlation between gene expression
      and patient survival. Overall, both genes behaved similarly (p<0.001). These
      results suggest a co-regulation of KLK10 and KLK11 expression in lung and a lack
      of KLK10 suppressor role in NSCLC. Finally, our findings indicate that these
      genes are likely involved in normal physiology processes in bronchus.

PMID- 16800741
TI  - mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the
      discrimination of benign prostatic hyperplasia from prostate cancer after needle
      prostate biopsy.
AB  - Kallikrein 11 (KLK11, TLSP, hippostatin) is a member of the human kallikrein gene
      family, which includes PSA, KLK2 and 12 other members, all localized on
      chromosome 19q13.4. The aim of this study was to investigate whether KLK11
      expression could be used to discriminate prostate cancer (CaP) from benign
      prostatic hyperplasia (BPH) in needle prostate biopsies. We analyzed the
      expression of the prostate-type variant of the KLK11 gene in 64 CaP and BPH
      tissues obtained by transrectal ultrasound-guided needle biopsy. Reverse
      transcription (RT), PCR and image analysis methodologies were developed and used.
      Of the 42 BPH tissues examined, only 10 (23.8%) were positive for prostate-type
      KLK11 expression, while of the 22 CaP patients, 12 (54.5%) were KLK11-positive
      (p=0.025). Logistic regression and receiver operating characteristic curve
      analyses demonstrated that KLK11 expression has a significant discriminatory
      value (crude odds ratio=3.84, p=0.016; area under the curve, 0.65, 95% CI 0.51
      0.80) between CaP and BPH in needle prostate biopsies.

PMID- 16800742
TI  - The epigenetic basis for the aberrant expression of kallikreins in human cancers.
AB  - The tissue kallikrein gene family consists of 15 genes tandemly arranged on human
      chromosome 19q13.4. Most kallikrein genes are characterized by aberrant
      expression patterns in various human cancers, a feature that makes them ideal
      cancer biomarkers. In the present study, we investigated the effect of the
      epigenetic drug compound 5-aza-2'-deoxycytidine on the expression of
      downregulated kallikrein genes in prostate, breast, and ovarian cancer cell
      lines. Reactivation of multiple kallikrein genes was observed, although some of
      these genes do not contain CpG islands in their genomic sequence. Epigenetic
      regulation provides a new mechanism for the pharmacological modulation of
      kallikreins in human cancers with putative therapeutic implications.

PMID- 16800743
TI  - Improved prostate cancer detection with a human kallikrein 11 and percentage free
      PSA-based artificial neural network.
AB  - Human kallikrein 11 (hK11) was evaluated in a percentage free PSA-based
      artificial neural network (ANN) to reduce unnecessary prostate biopsies. Serum
      samples from 357 patients with (n=132) and without (n=225) prostate cancer (PCa)
      were analyzed and ANN models were constructed and compared to all parameters. The
      discriminatory power of hK11 was lower than that of PSA, but receiver operator
      characteristic (ROC) analyses demonstrated significantly larger areas under the
      curves for the ANN compared to all other parameters. ANNs with hK11 may lead to a
      further reduction in unnecessary prostate biopsies, especially when analyzing
      patients with less than 15% free PSA.

PMID- 16800744
TI  - Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases
      the malignant phenotype of ovarian cancer cells.
AB  - The human tissue kallikrein family of serine proteases (hK1-hK15 encoded by the
      genes KLK1-KLK15) is involved in several cancer-related processes. Accumulating
      evidence suggests that certain tissue kallikreins are part of an enzymatic
      cascade pathway that is activated in ovarian cancer and other malignant diseases.
      In the present study, OV-MZ-6 ovarian cancer cells were stably co-transfected
      with plasmids expressing hK4, hK5, hK6, and hK7. These cells displayed similar
      proliferative capacity as the vector-transfected control cells (which do not
      express any of the four tissue kallikreins), but showed significantly increased
      invasive behavior in an in vitro Matrigel invasion assay (p<0.01; Mann-Whitney U
      test). For in vivo analysis, the cancer cells were inoculated into the peritoneum
      of nude mice. Simultaneous expression of hK4, hK5, hK6, and hK7 resulted in a
      remarkable 92% mean increase in tumor burden compared to the vector-control cell
      line. Five out of 14 mice in the 'tissue kallikrein overexpressing' group
      displayed a tumor/situs ratio greater than 0.198, while this weight limit was not
      exceeded at all in the vector control group consisting of 13 mice (p=0.017; chi2
      test). Our results strongly support the view that tumor-associated overexpression
      of tissue kallikreins contributes to ovarian cancer progression.

PMID- 16800745
TI  - Inhibition profiles of human tissue kallikreins by serine protease inhibitors.
AB  - Accumulated evidence has shown that human tissue kallikreins (hKs), a group of 15
      homologous secreted serine proteases, are novel cancer biomarkers. We report here
      the inhibition profiles of selected hKs, including hK5, hK7, hK8, hK11, hK12,
      hK13, and hK14, by several common serine protease inhibitors (serpins) found in
      plasma. The association constants for the binding of serpins to kallikreins were
      determined and compared. Protein C inhibitor was found to be the fastest-binding
      serpin for most of these hKs. alpha2-Antiplasmin, alpha1-antichymotrypsin, and
      alpha1-antitrypsin also showed rapid inhibition of certain hKs. Kallistatin
      exhibited fast inhibition only with hK7. Our data demonstrate that these hKs are
      specifically regulated by certain serpins and their distinct inhibition profiles
      will be valuable aids in various aspects of kallikrein research.

PMID- 16800746
TI  - Kallikrein-mediated cell signalling: targeting proteinase-activated receptors
      (PARs).
AB  - We tested the hypothesis that human tissue kallikreins (hKs) may regulate signal
      transduction by cleaving and activating proteinase-activated receptors (PARs). We
      found that hK5, 6 and 14 cleaved PAR N-terminal peptide sequences representing
      the cleavage/activation motifs of human PAR1 and PAR2 to yield receptor
      activating peptides. hK5, 6 and 14 activated calcium signalling in rat PAR2
      expressing (but not background) KNRK cells. Calcium signalling in HEK cells co
      expressing human PAR1 and PAR2 was also triggered by hK14 (via PAR1 and PAR2) and
      hK6 (via PAR2). In isolated rat platelets that do not express PAR1, but signal
      via PAR4, hK14 also activated PAR-dependent calcium signalling responses and
      triggered aggregation. The aggregation response elicited by hK14 was in contrast
      to the lack of aggregation triggered by hK5 and 6. hK14 also caused
      vasorelaxation in a phenylephrine-preconstricted rat aorta ring assay and
      triggered oedema in an in vivo model of murine paw inflammation. We propose that,
      like thrombin and trypsin, the kallikreins must now be considered as important
      'hormonal' regulators of tissue function, very likely acting in part via PARs.

PMID- 16800747
TI  - A long-wavelength fluorescent glucose biosensor based on bioconjugates of
      galactose/glucose binding protein and Nile Red derivatives.
AB  - BACKGROUND: Fluorescent biosensors based on galactose/glucose binding protein
      (GGBP) and environmentally sensitive derivatives of the phenoxazine dye Nile Red
      are described. These biosensors are proposed as the sensing platform for a
      minimally invasive, continuous glucose monitoring system that can be implanted
      under the skin and read transdermally using an external fluorometer. METHODS: To
      construct the biosensors, the thiol-reactive Nile Red derivatives INR and IANR
      were prepared and conjugated to GGBP proteins possessing cysteine mutations that
      were designed for optimal site-specific fluorophore attachment. The attachment
      sites were selected to maximize the local environment change for attached dyes
      between the bound and unbound conformations of GGBP. RESULTS: Fluorescence
      responses at the selected cysteine sites of GGBP upon binding to glucose showed
      that the conjugates typically yielded fluorescence emission around 640-650 nm
      with up to 50% changes in fluorescence intensity. Conjugate E149C/A213C/L238S INR
      GGBP also displayed glucose binding in the human physiological range (K (D) = 7.4
      mM). CONCLUSIONS: The phenoxazine derivatives fluoresced at longer wavelengths
      (>600 nm) approaching the near-infrared spectral window, where interference from
      scattering and tissue absorbance are minimal. Ultimately, we expect that
      monitoring systems based on GGBP and longwavelength dyes will be implanted for up
      to 6 months and can be used to transmit information through the skin to an
      external monitor.

PMID- 16800748
TI  - Glucose sensors based on microcapsules containing an orange/red competitive
      binding resonance energy transfer assay.
AB  - Fluorescent sensing systems offer the potential for noninvasive monitoring with
      implantable devices, but they require carrier technologies that provide suitable
      immobilization, accessibility, and biocompatibility while maintaining adequate
      response characteristics. A recent development towards this goal is a highly
      specific and sensitive competitive binding assay for glucose using apo-glucose
      oxidase (apo-GOx) as the recognition element and dextran as the competing ligand;
      this has been demonstrated as a glucose sensor system by encapsulating the
      competitive binding assay in semipermeable microcapsule carriers. This paper
      describes the extension of this sensor design to longer wavelengths in an attempt
      to increase the applicability to in vivo monitoring. The glucose sensitivity of
      the tetramethylrhodamine isothiocyanate-dextran (TD) and cyanine Cy5-apo-GOx
      (CAG) complexes showed five to 10 times greater specificity for beta-D-glucose
      over other sugars. Microcapsules loaded with TD/CAG complexes exhibited a linear,
      totally reversible response in the range of 0-720 mg/dL, with a sensitivity
      (percent change in intensity ratio) of 0.06%/(mg/dL). The decrease in sensitivity
      observed with the use of longer-wavelength dyes is most likely to be compensated
      with the deeper penetration of light and reduced tissue scattering. These
      findings imply that the encapsulation of sensing assay elements in microcapsules
      is a simple and translatable method for the fabrication of stable biosensors, and
      optimization of resonance energy transfer pairs and assay component preparation
      will further improve the response to approach clinically relevant performance.

PMID- 16800749
TI  - Continuous glucose sensing with fluorescent thin-film hydrogels. 2. Fiber optic
      sensor fabrication and in vitro testing.
AB  - BACKGROUND: There continues to be a need for better sensors for continuous
      glucose monitoring. We are working on a two-component sensing system based on a
      viologen boronic acid and a fluorescent dye, which are immobilized in a hydrogel.
      This system has the potential for further development into a real-time glucose
      monitoring device. The current study reports the fabrication of sensors using
      preformed hydrogels and the first in vitro monitoring of glucose concentrations
      in a prototype sensor configuration. METHODS: Glucose sensing hydrogels
      containing a fluorescent dye and viologen boronic acid quencher were preformed in
      a mold. These preformed hydrogels were then attached to the distal end of a
      plastic fiber optic cable using different adhesives to prepare the in vitro
      sensors. These sensors were connected to a flow cell and monitored using a
      fluorescence spectrometer. The fluorescence emitted by the hydrogel changes
      depending on the glucose concentration. Hydrogel components were modified in
      order to optimize the performance of the sensors. RESULTS: A soft tissue adhesive
      used by veterinarians was found to be an effective adhesive for bonding the
      hydrogel to the fiber tip. This adhesive did not affect the glucose sensing
      ability of the hydrogels after fabrication. Several sensors were fabricated with
      varying composition of sensing elements, and all of them showed stable and
      reversible glucose response. The glucose signal was found to be stable over
      months on repeated testing. Glucose sensing studies using the sensors with
      hydrogels containing different compositions of sensing elements showed that the
      ratio of dye to quencher is an important parameter in determining the magnitude
      and linearity of glucose response in the biological range. The response time of
      the sensor was shown to be dependent on the hydrophilicity of the hydrogels.
      Modifying the hydrogels with ionic comonomers shortened the response time.
      CONCLUSIONS: The combination of the anionic dye 2 and viologen-based boronic acid
      1 immobilized in a 2-hydroxyethyl methacrylate hydrogel functions well in a fiber
      optic configuration. This preliminary study suggests that the two-component
      sensing system has several advantages in terms of stability and ease of
      fabrication. Improvement of the configuration of the sensor and further
      development of the sensor towards application for in vitro study are underway.

PMID- 16800750
TI  - Enzymatic fluorescent microsphere glucose sensors:evaluation of response under
      dynamic conditions.
AB  - Most previous attempts at the development of a "smart tattoo" for glucose
      monitoring in diabetes--implantable fluorescent microspheres that can be
      implanted intradermally and interrogated transdermally using light--have focused
      on the encapsulation of a competitive binding assay for glucose within hydrogel
      microspheres or polyelectrolyte microcapsules. We recently reported on the
      development of a microsphere sensor based on an enzymatic scheme, combined with
      an oxygen-quenched fluorescent reporter element. A novel feature of this design
      is the use of polyelectrolyte multilayer nanofilms, which are assembled stepwise
      on the surface of the microspheres, for modulation of glucose and oxygen mass
      transport, allowing them to be designed for sensitive and safe operation within
      the "oxygen deficit" present in the skin. In this work, a flow-through sensor
      testing apparatus was used to demonstrate the reversible response of the sensors
      under controlled, dynamic conditions. The sensors were shown to be sensitive over
      at least 0-140 mg/dL glucose, with a response time of less than 2 min. This
      report also identifies some current problems with the approach, and gives
      potential solutions towards the development of a practical implantable sensor for
      glucose monitoring in diabetes.

PMID- 16800751
TI  - In vivo performance evaluation of a transdermal near- infrared fluorescence
      resonance energy transfer affinity sensor for continuous glucose monitoring.
AB  - The in vivo performance of a transdermal near-infrared fluorescence resonance
      energy transfer (FRET) affinity sensor was investigated in hairless rats, in
      order to validate its feasibility for glucose monitoring in humans. The sensor
      itself consists of a small hollow fiber implanted in dermal skin tissue,
      containing glucose-sensitive assay chemistry composed of agarose-immobilized
      Concanavalin A (ConA) and free dextran. The glucose-dependent fluorescence change
      is based on FRET between near-infrared-compatible donor and quencher dyes that
      are chemically linked to dextran and ConA, respectively. We conducted an acute in
      vivo evaluation of transdermal sensors with an optical fiber-coupled setup over 4
      h, and a chronic in vivo evaluation of fully implanted sensors for up to 16 days.
      The fiber-coupled sensors followed trends of blood glucose concentrations very
      well with a delay of less than 5 min. The acute performance of the implanted
      sensors at the day of implantation was similar to that of the fiber-coupled
      sensors. After 2 weeks the implanted sensors remained functional, evidenced by an
      adequate correlation between sensor signal and changes in blood glucose
      excursions, but exhibited delays of approximately 10-15 min. Preliminary
      characterization of host response showed signs of mild inflammations around the
      implanted sensor, which were characterized by formation of a 10-20-microm-thick
      collagen band, typical for capsule formation. An acute study of systemic ConA
      biotoxicity was also conducted. A histological analysis of various organs and of
      clinical chemistry data showed no significant differences between rats receiving
      intradermal injections of ConA at 10 times the concentration in the sensor and
      rats in a control group (injection of saline solution). The absence of a
      toxicological or systemic response to ConA at a 10-fold larger amount than in the
      sensor should dispel concerns over the in vivo safety of ConA-based sensors. This
      study clearly demonstrates the feasibility of the proposed transdermal FRET-based
      sensor interrogation concept for glucose monitoring.

PMID- 16800752
TI  - Fluorescent measurement in the non-invasive contact lens glucose sensor.
AB  - BACKGROUND: The purpose of the present study was to determine the effectiveness
      of software in the hand-held photofluorometer permitting the monitoring of a
      second fluorescent signal to improve a contact lens glucose sensor for the non
      invasive monitoring of glucose. METHODS: One fasting normal patient was given an
      oral challenge consisting of 75 mL of Sustacol (Thomson Micromedex, Greenwood,
      CO). The two contact lens fluorescent signals and fingerstick blood glucose were
      measured over a 3-h period. RESULTS: Subtracting the second fluorescent signal
      from the main signal produced a product that appeared to track blood glucose
      well. The contact lens was comfortable and well tolerated. CONCLUSION: The
      biwavelength contact lens glucose sensor shows promise as a non-invasive home
      glucose monitor.

PMID- 16800753
TI  - Evaluation of factors affecting CGMS calibration.
AB  - BACKGROUND: The optimal number/timing of calibrations entered into the CGMS
      (Medtronic MiniMed, Northridge, CA) continuous glucose monitoring system have not
      been previously described. METHODS: Fifty subjects with Type 1 diabetes mellitus
      (10-18 years old) were hospitalized in a clinical research center for
      approximately 24 h on two separate days. CGMS and OneTouch Ultra meter (LifeScan,
      Milpitas, CA) data were obtained. The CGMS was retrospectively recalibrated using
      the Ultra data varying the number and timing of calibrations. Resulting CGMS
      values were compared against laboratory reference values. RESULTS: There was a
      modest improvement in accuracy with increasing number of calibrations. The median
      relative absolute deviation (RAD) was 14%, 15%, 13%, and 13% when using three,
      four, five, and seven calibration values, respectively (P < 0.001). Corresponding
      percentages of CGMS-reference pairs meeting the International Organisation for
      Standardisation criteria were 66%, 67%, 71%, and 72% (P < 0.001). Nighttime
      accuracy improved when daytime calibrations (pre-lunch and pre-dinner) were
      removed leaving only two calibrations at 9 p.m. and 6 a.m. (median difference, -2
      vs. -9 mg/dL, P < 0.001; median RAD, 12% vs. 15%, P = 0.001). Accuracy was better
      on visits where the average absolute rate of glucose change at the times of
      calibration was lower. On visits with average absolute rates <0.5, 0.5 to <1.0,
      1.0 to <1.5, and >or=1.5 mg/dL/min, median RAD values were 13% versus 14% versus
      17% versus 19%, respectively (P = 0.05). CONCLUSIONS: Although accuracy is
      slightly improved with more calibrations, the timing of the calibrations appears
      more important. Modifying the algorithm to put less weight on daytime
      calibrations for nighttime values and calibrating during times of relative
      glucose stability may have greater impact on accuracy.

PMID- 16800754
TI  - Evaluation of the accuracy of a microdialysis-based glucose sensor during insulin
      induced hypoglycemia, its recovery, and post-hypoglycemic hyperglycemia in
      humans.
AB  - BACKGROUND: These studies were designed to evaluate the accuracy of a
      microdialysis-based subcutaneous glucose sensor (GlucoDay, A. Menarini
      Diagnostics, Firenze, Italy) compared with a standard reference method of plasma
      glucose measurement during insulin-induced hypoglycemia. RESEARCH DESIGN AND
      METHODS: Nine subjects without diabetes were studied in eu-, hypo-, and
      hyperglycemia (clamp technique). The GlucoDay was calibrated against one
      arterialized plasma glucose measurement (Glucose Analyzer, Beckman, Brea, CA),
      and plasma glucose estimates every 3 min were compared with paired plasma glucose
      values. RESULTS: Accuracy of glucose estimates was not homogeneously distributed
      among subjects and depended on stability of the sensor's current signal during
      spontaneous euglycemia (R +/- -0.68). Linear regression analysis showed a good
      correlation between the two methods of measurement (R = 0.9), Deming regression
      showed the inclusion of the unit in the confidence interval of the slope (slope
      0.95, 95% confidence interval 0.87-1.02), and the accuracy of the GlucoDay
      reached 40 +/- 15% (American Diabetes Association criteria). The mean relative
      difference was 6 +/- 8% in euglycemia, 13 +/- 14% during plasma glucose fall, 5
      +/- 22% in the hypoglycemic plateau, and -14 +/- 16% during recovery from
      hypoglycemia. The Bland-Altman analysis indicated a bias of -1.9 +/- 16.6 mg/dL,
      whereas the Error Grid Analysis showed 94% of the Gluco- Day measurements in the
      acceptable zones of the grid. The time to reach the glycemic nadir was longer
      when measured with the GlucoDay (90 +/- 5 vs. 72.5 +/- 9 min, P < 0.05). However,
      absolute values of glycemic nadir, time spent in hypoglycemia, and the rate of
      fall of glycemia and the rate of recovery from the hypoglycemia were not
      statistically different. CONCLUSIONS: GlucoDay closely monitors changes in plasma
      glucose before, during, and after hypoglycemia. However, these results can be
      achieved only if calibration of the GlucoDay is performed under conditions of
      sensor signal stability. Similar studies have to be performed in subjects with
      diabetes to validate the GlucoDay system.

PMID- 16800756
TI  - Improving the quality of self-monitoring blood glucose measurement: a study in
      reducing calibration errors.
AB  - BACKGROUND: Two independent studies reported that 16% of people who self-monitor
      blood glucose used incorrectly coded meters. The degree of analytical error,
      however, was not characterized. Our study objectives were to demonstrate that
      miscoding can cause analytical errors and to characterize the potential amount of
      bias that can occur. The impact of calibration error with three selfblood glucose
      monitoring systems (BGMSs), one of which has an autocoding feature, is reported.
      METHODS: Fresh capillary fingerstick blood from 50 subjects, 18 men and 32 women
      ranging in age from 23 to 82 years, was used to measure glucose with three BGMSs.
      Two BGMSs required manual coding and were purposely miscoded using numbers
      different from the one recommended for the reagent lot used. Two properly coded
      meters of each BGMS were included to assess within-system variability. Different
      reagent lots were used to challenge a third system that had autocoding capability
      and could not be miscoded. RESULTS: Some within-system comparisons showed
      deviations of greater than +/-30% when results obtained with miscoded meters were
      compared with data obtained with ones programmed using the correct code number.
      Similar erroneous results were found when the miscoded meter results were
      compared with those obtained with a glucose analyzer. For some miscoded meter and
      test strip combinations, error grid analysis showed that 90% of results fell into
      zones indicating altered clinical action. Such inaccuracies were not found with
      the BGMS having the autocoding feature. CONCLUSIONS: When certain meter code
      number settings of two BGMSs were used in conjunction with test strips having
      code numbers that did not match, statistically and clinically inaccurate results
      were obtained. Coding errors resulted in analytical errors of greater than +/-30%
      (-31.6 to +60.9%). These results confirm the value of a BGMS with an automatic
      coding feature.

PMID- 16800755
TI  - Transient and steady-state euglycemic clamp validation of a model for glycemic
      control and insulin sensitivity testing.
AB  - BACKGROUND: There is an urgent need for a simple and accurate measure of insulin
      sensitivity to diagnose insulin resistance in the general population and quantify
      changes due to clinical intervention. A new physiological control model of
      glucose and insulin metabolism is validated with the euglycemic-hyperinsulinemic
      clamp during steady and transient states. METHODS: The data consist of n = 60 (15
      lean, 15 overweight, 15 obese, and 15 morbidly obese) euglycemic-hyperinsulinemic
      clamp trials performed on normoglycemic insulin-resistant individuals. The
      glucose and insulin model is fitted using an integral-based method. Correlations
      between clamp-derived insulin sensitivity index (ISI) and the model's insulin
      sensitivity parameter (SI) are obtained during steady and transient states.
      Results are compared with log-homeostasis model assessment (HOMA), a widely used
      fasting surrogate for insulin sensitivity. RESULTS: Correlation between model
      based insulin sensitivity, SI, and ISIG (ISI normalized by steady-state glucose)
      is r = 0.99 (n = 60) at steady state and r = 0.97 at transient state,
      respectively. Correlations did not significantly change across subgroups, with
      narrow 95% confidence intervals. Log-HOMA correlations are r=-0.72 to SI and r=
      0.71 to ISIG for the overall population but are significantly lower in the
      subgroups, with wide 95% confidence intervals. CONCLUSIONS: The model-based
      insulin sensitivity parameter, SI, highly correlates to ISIG in all subgroups,
      even when only considering a transient state. The high correlation of SI offers
      the potential for a short, simple yet highly correlated, model-based assessment
      of insulin sensitivity that is not currently available.

PMID- 16800757
TI  - In vitro stability of insulin lispro in continuous subcutaneous insulin infusion.
AB  - BACKGROUND: The stability of insulin lispro for use in continuous subcutaneous
      insulin infusion (CSII) therapy was evaluated using a stress test incorporating
      high temperature and mechanical agitation combined with simulated basal/bolus
      administration. METHODS: Insulin lispro formulation contained in MiniMed 507c
      (Medtronic MiniMed, Sylmar, CA), H-TRONplus (Disetronic Medical Systems, St.
      Paul, MN), and D-TRON CSII (Disetronic Medtronic Systems) devices was subjected
      to a stress test involving exposure to elevated temperature (37 degrees C) and
      mechanical agitation (shaking at 100 strokes/min) for 7 days. CSII devices were
      programmed for continuous infusion at 0.8 U/h (19.2 U/day), and three 6-U bolus
      doses were also manually delivered each day (18 U/day). Formulation infused from
      the devices was collected every 24 h over the 7-day study. The material obtained
      from each 24-h period was analyzed to assess the physicochemical properties of
      insulin lispro and the overall formulation. Insulin lispro potency, purity, high
      molecular-weight protein (HMWP), and m-cresol content were determined using high
      performance liquid chromatographic methods. Solution pH, delivered volume, and
      formulation physical appearance were also evaluated. RESULTS: The pH of the
      infused formulation remained unchanged throughout the entire study. Insulin
      lispro potency for each device remained within 95-105% of label claim each day of
      the stress test, indicating that adsorption or surface-induced denaturation of
      insulin lispro did not occur. Levels of insulin lispro deamidated at position 21
      in the A-chain were essentially constant during the 7-day stress test. A time
      dependent increase in HMWP and other insulin lispro chemical transformation
      products was observed over the testing period for each device. However, the
      levels of these known degradation products remained well below published
      specifications for these analytical properties. The concentration of the
      antimicrobial agent, m-cresol, was decreased because of absorption, but the
      levels remained sufficient to provide protection against microbial contamination.
      Total delivered volume results were in good agreement with expected values and
      confirmed that formulation viscosity remained unchanged. Samples collected from
      the infusion sets were clear and free of precipitates. Occlusion alarms did not
      occur, and no other electronic or mechanical malfunctions of the CSII devices
      were encountered. CONCLUSIONS: Insulin lispro demonstrates appropriate
      physicochemical stability for use in MiniMed 507c, H-TRONplus, and D-TRON CSII
      devices.

PMID- 16800758
TI  - Transdermal delivery of CaCO3-nanoparticles containing insulin.
AB  - BACKGROUND: This study evaluates the pharmacokinetic and pharmacodynamic effects
      of a transdermally delivered insulin using novel CaCO(3)-nanoparticles in normal
      mice and those with diabetes. METHODS: CaCO3-nanoparticles encapsulating insulin
      (nanoinsulin) were transdermally applied to the back skin of normal ddY mice and
      dB/dB and kkAy mice with diabetes after fasting for 1 h. Serum insulin levels of
      ddY mice were analyzed by enzyme immunoassay, and blood glucose of normal mice
      and those with diabetes was monitored. RESULTS: Maximum serum insulin was 67.1 +/
      25.9 microIU/mL at 4 h with 200 microg of transdermal nanoinsulin in ddY mice,
      whereas that after subcutaneous injection of 3 microg of monomer insulin was 462
      +/- 20.9 microIU/mL at 20 min. Transdermal nanoinsulin decreased glucose levels
      in a dose-dependent manner. A maximum decrease in blood glucose of 48.3 +/- 3.9%
      (ddY), 32.5 +/- 9.8% (dB/dB), and 26.2 +/- 7.6% (kkAy) after 6 h was observed
      with 200 microg of transdermal nanoinsulin, compared with 64.1+/-1.0% (ddY), 57.9
      +/-3.4% (dB/dB), and 24.1 +/- 6.7% (kkAy) after 1 h with 3 microg of subcutaneous
      monomer insulin. Insulin bioavailability until 6 h with transdermal nanoinsulin
      in ddY mice was 0.9% based on serum insulin level and 2.0% on pharmacodynamic
      blood glucose-lowering effects. CONCLUSIONS: This CaCO(3)-nanoparticle system
      successfully delivered insulin transdermally, as evidenced by a significant
      sustained decrease in blood glucose in normal mice and those with diabetes. These
      results support the feasibility of developing transdermal nanoinsulin for human
      applications.

PMID- 16800760
TI  - Incretin mimetics and dipeptidyl peptidase-IV inhibitors: a review of emerging
      therapies for type 2 diabetes.
AB  - Type 2 diabetes is thought to develop as a result of progressive beta-cell
      dysfunction in the setting of insulin resistance, leading to increased risks of
      microvascular and macrovascular complications. Type 2 diabetes is currently
      treated with diet and exercise, followed by oral drug therapy, and finally
      exogenous insulin. While this approach is known to improve glycemic control, none
      of the currently available therapies significantly improve beta-cell function. In
      addition, this approach does not address defects in hormonal secretion thought to
      play key roles in the pathophysiology of type 2 diabetes. Type 2 diabetes is
      characterized by excess glucagon secretion and insufficient secretion of the
      hormone amylin from the pancreatic beta-cell. In addition, individuals with type
      2 diabetes demonstrate insufficient secretion of the incretin hormone glucagon
      like peptide-1 (GLP-1). Novel therapies that leverage the so-called "incretin
      effect" of GLP-1 (including the incretin mimetics and dipeptidyl peptidase-IV
      (DPP-IV) inhibitors) are being actively developed for the management of type 2
      diabetes. Incretin mimetics are either derivatives of GLP-1, modified to resist
      proteolysis, or are novel peptides that share glucoregulatory functions with GLP
      1 and are naturally resistant to proteolysis. DPP-IV inhibitors enhance the
      concentration of endogenous GLP-1 by limiting proteolysis of native GLP-1. With
      the approval of exenatide- the first "incretin mimetic"-treatment of type 2
      diabetes will no doubt be changed. An understanding of the effects of these
      compounds will be needed to enhance the clinical approach to diabetes treatment.

PMID- 16800759
TI  - The switch from sulfonylurea to preprandial short- acting insulin analog
      substitution has an immediate and comprehensive beta-cell protective effect in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Supplementary insulin therapy provides assistance to meal-time
      insulin secretion in patients with type 2 diabetes and may have protective
      effects on beta-cell function. METHODS: This study explored the immediate effect
      of supplementary insulin therapy on beta- cell function in patients with
      glimepiride monotherapy (five women, 15 men; 61.8 +/- 6.4 years old; body mass
      index, 31.1 +/- 4.4 kg/m(2); hemoglobin A1c, 7.0 +/- 1.3%). After 1 week of
      continued glimiperide therapy, the patients were randomized either to continue
      with their oral treatment or to switch to a fixed-dose supplementary insulin
      therapy (8 U of insulin aspart subcutaneously before each meal) for another week.
      Oral glucose tolerance tests (OGTTs) after drug uptake were performed at days 7
      and 14, with measurement of glucose, insulin, C-peptide, intact and total
      proinsulin, glucagon, lactate, free fatty acids, and adiponectin. RESULTS:
      Significant reductions from baseline were seen in the supplementary insulin
      therapy group for the fasting values of insulin (from 13.1 +/- 5.1 microU/mL to
      10.6 +/- 5.2 microU/mL, P < 0.01), intact proinsulin (from 18.3 +/- 11.2 pmol/L
      to 10.3 +/- 4.6 pmol/L, P micro 0.05), total proinsulin (from 43.3 +/- 22.7
      pmol/L to 29.7 +/- 14.5 pmol/L, P < 0.01), split proinsulin (from 24.9 +/- 13.8
      pmol/L to 19.4 +/- 10.8 pmol/L, P micro 0.01), and the degree of beta-cell
      dysfunction (P < 0.05). Also, lower values for intact and total proinsulin and
      split proinsulin in the OGTT were observed in this group during the OGTT at the
      end point, while no changes at all occurred in the glimepiride group.
      CONCLUSIONS: A fixed low-dose preprandial insulin aspart therapy resulted in an
      overall beta-cell protection with an improved fasting beta-cell secretion profile
      already within 1 week. Our study indicates that supplementary insulin therapy
      might be a reasonable alternative to bedtime basal insulin injections for
      initiation of insulin therapy in patients with type 2 diabetes.

PMID- 16800761
TI  - Implantable insulin pump therapy: an unusual presentation of a catheter-related
      complication.
AB  - We report the case of a 63-year-old man who has a 19-year history of involvement
      in the implantable insulin pump program at Johns Hopkins University. After his
      most recent pump implantation in February 2004, his 24-h insulin requirement
      gradually increased from a baseline of 75 units to a peak of almost 500 units in
      June 2005. Surprisingly, insulin delivery from the pump and glycemic control
      remained satisfactory despite the dramatic change in insulin requirement.
      Laparotomy revealed a fibrous mass in the peritoneal cavity, with the track of
      the catheter extending into the mass. Insulin requirement declined post-resection
      of the mass and relocation of the catheter tip.

PMID- 16800762
TI  - Continuous glucose monitoring in normal mice and mice with prediabetes and
      diabetes.
AB  - It is well established that the key to minimizing diabetes-associated
      complications, in both type 1 and type 2 diabetes, is tight regulation of blood
      glucose levels. Currently the major approach to regulating blood glucose levels
      in patients with diabetes relies on external blood glucose monitors. However,
      poor patient compliance usually results in limited insights into the dynamic
      range of blood glucose levels (i.e., hyperglycemia vs. hypoglycemia), and
      inadequate prediction and control of blood glucose levels in these patients.
      Implantable glucose sensors hold promise for controlling blood glucose levels,
      but currently these sensors have only limited in vivo life span. Recently we have
      developed an extremely robust murine model for implantable glucose sensors. In
      the present study, we have extended this model by developing a complete system
      for real-time continuous glucose monitoring in normal mice and mice with
      prediabetes and diabetes (type 1). These studies demonstrated that (1) glucose
      sensors can be implanted and maintained subcutaneously in the mice; (2)
      continuous glucose sensor data can be obtained for at least 5 days; and (3)
      subcutaneous blood glucose sensing paralleled blood glucose levels in normal mice
      and mice with prediabetes and diabetes. Subcutaneous blood glucose sensing also
      successfully tracked changes in blood glucose levels induced in the mice with
      diabetes by administration of oral glucose or insulin. These results mirror the
      results for subcutaneous blood glucose sensing seen in both normal subjects and
      patients with diabetes, and therefore validate both our continuous glucose
      monitoring system in the mouse, and the use of the mouse as a model for
      implantable glucose sensing in vivo.

PMID- 16800763
TI  - Analysis: overcoming the "valley of death": mouse models to accelerate
      translational research.

PMID- 16800766
TI  - Retrospective pilot feedback survey of 200 users of the AIDA Version 4
      Educational Diabetes Program. 1--Quantitative Survey Data.
AB  - This column reports a detailed, questionnaire-based, post-release feedback survey
      of 200 users of the AIDA version 4 educational diabetes simulator. AIDA is a
      freeware computer program that permits the interactive simulation of plasma
      insulin and blood glucose profiles for educational, demonstration, self-learning,
      and research purposes. Since its Internet launch in 1996 over 700,000 visits have
      been logged to the AIDA Websites-including www.2aida.org-and over 200,000 program
      copies have been downloaded free-of-charge. The main goals of the current study
      were: (1) to establish what people have thought about the AIDA program, (2) to
      assess the utility of the software, and (3) to ascertain how much people have
      actually used it. An analysis was therefore undertaken of the first 200 feedback
      forms that were returned by AIDA users. The questionnaire-based survey
      methodology was found to be robust and reliable. Feedback forms were received
      from participants in 21 countries. One hundred six of 209 responses (50.7%) were
      received from people with diabetes, and 36 of 209 (17.2%) from relatives of
      patients, with lesser numbers from doctors, students, diabetes educators, nurses,
      pharmacists, and other end users. Please note some respondents fulfilled more
      than one end-user category, hence the denominator <200; for example, someone with
      diabetes who was also a doctor. This study has established the feasibility of
      using a simple feedback form to survey a substantial number of diabetes software
      users. In addition, it has yielded interesting data in terms of who are the main
      users of the AIDA program, and has also provided technical (computer) information
      that has aided the release of a freeware upgrade to the software. In general,
      users reported finding the program to be of educational value. The majority also
      felt it would be of interest to diabetes educators and people with diabetes. Most
      were clear about its limitations as a simulator-based learning tool. The
      implications of these findings will be discussed.

PMID- 16800768
TI  - Intact anthocyanins and metabolites in rat urine and plasma after 3 months of
      anthocyanin supplementation.
AB  - Anthocyanins are polyphenols responsible for most red to purple colors in plants.
      Human consumption of these pigments is increasing because of their potential
      health benefits and use as natural colorants. With more than 600 different
      anthocyanins found in nature, the impact of chemical structure on their
      absorption and metabolism needs to be investigated. Urine and plasma samples were
      collected from 32 rats receiving control diet or chokeberry-, bilberry-, and
      grape-enriched (3.85 g cyanidin 3-galatoside equivalent/kg) diet for 14 wk. Below
      2 micromol/l of anthocyanins and relatively higher levels of presumable
      metabolites were detected by high-performance liquid chromatography-photodiode
      array in the plasma. In the urine the total concentration of intact anthocyanins
      and methylated derivatives ranged from 17.4 (bilberry) to 52.6 (chokeberry)
      nmol/l. The type and number of anthocyanin glycosylations affected the absorption
      remarkably. Detection of an acylated anthocyanin in plasma and urine suggests
      bioavailability of these anthocyanin derivatives that are commonly found in
      commercially available colorants.

PMID- 16800769
TI  - Bioavailability of quercetin from berries and the diet.
AB  - Berries are a rich source of various polyphenols, including the flavonoid
      quercetin. In this article, the results of three intervention studies
      investigating the bioavailability of quercetin from berries are reviewed. In the
      first study, we investigated the short-term kinetics of quercetin after
      consumption of black currant juice and showed that quercetin is rapidly absorbed
      from it. In the second study, we showed that plasma quercetin levels increase up
      to 50% in subjects consuming 100 g/day of bilberries, black currants, and
      lingonberries as a part of their normal diets for 2 mo. In the third study,
      healthy subjects consumed a diet high or low in vegetables, berries, and other
      fruit for 6 wk. Quercetin concentrations nearly doubled in the high-vegetable, 
      berry, and -other fruit group and decreased by 30% in subjects consuming less of
      these foods than normally. The results showed that plasma quercetin is
      bioavailable from a diet containing berries and indicate that it may be a good
      biomarker of fruit and vegetable intake in general.

PMID- 16800770
TI  - Berry phenolics: antimicrobial properties and mechanisms of action against severe
      human pathogens.
AB  - Antimicrobial activity and mechanisms of phenolic extracts of 12 Nordic berries
      were studied against selected human pathogenic microbes. The most sensitive
      bacteria on berry phenolics were Helicobacter pylori and Bacillus cereus.
      Campylobacter jejuni and Candida albicans were inhibited only with phenolic
      extracts of cloudberry, raspberry, and strawberry, which all were rich in
      ellagitannins. Cloudberry extract gave strong microbicidic effects on the basis
      of plate count with all studied strains. However, fluorescence staining of liquid
      cultures of virulent Salmonella showed viable cells not detectable by plate count
      adhering to cloudberry extract, whereas Staphylococcus aureus cells adhered to
      berry extracts were dead on the basis of their fluorescence and plate count.
      Phenolic extracts of cloudberry and raspberry disintegrated the outer membrane of
      examined Salmonella strains as indicated by 1-N-phenylnaphthylamine (NPN) uptake
      increase and analysis of liberation of [14C]galactose- lipopolysaccharide. Gallic
      acid effectively permeabilized the tested Salmonella strains, and significant
      increase in the NPN uptake was recorded. The stability of berry phenolics and
      their antimicrobial activity in berries stored frozen for a year were examined
      using Escherichia coli and nonvirulent Salmonella enterica sv. Typhimurium. The
      amount of phenolic compounds decreased in all berries, but their antimicrobial
      activity was not influenced accordingly. Cloudberry, in particular, showed
      constantly strong antimicrobial activity during the storage.

PMID- 16800771
TI  - Protection against esophageal cancer in rodents with lyophilized berries:
      potential mechanisms.
AB  - For several years, our laboratory has been evaluating the ability of lyophilized
      (freeze-dried) black raspberries (Rubus occidentalis, BRBs), blackberries (R.
      fructicosus, BBs), and strawberries (Fragaria ananasia, STRWs) to inhibit
      carcinogen-induced cancer in the rodent esophagus. To assure "standardized" berry
      preparations for study, each berry type is of the same cultivar, picked at about
      the same degree of ripeness, washed and frozen within 2-4 h of the time of
      picking, and freeze-dried under conditions that preserve the components in the
      berries. Some of the known chemopreventive agents in berries include vitamins A,
      C, and E and folic acid; calcium and selenium; beta-carotene, alpha-carotene, and
      lutein; polyphenols such as ellagic acid, ferulic acid, p-coumaric acid,
      quercetin, and several anthocyanins; and phytosterols such as beta-sitosterol,
      stigmasterol, and kaempferol. In initial bioassays, freeze-dried STRW, BRB, and
      BB powders were mixed into AIN-76A synthetic diet at concentrations of 5% and 10%
      and fed to Fischer 344 rats before, during, and after treatment with the
      esophageal carcinogen N-nitrosomethylbenzylamine (NMBA). At 25 wk of the
      bioassay, all three berry types were found to inhibit the number of esophageal
      tumors (papillomas) in NMBA-treated animals by 24-56% relative to NMBA controls.
      This inhibition correlated with reductions in the formation of the NMBA-induced
      O6-methylguanine adduct in esophageal DNA, suggesting that the berries influenced
      the metabolism of NMBA leading to reduced DNA damage. Studies are ongoing to
      determine the mechanisms by which berries influence NMBA metabolism and DNA
      adduct formation. BRBs and STRWs were also tested in a postinitiation scheme and
      were found to inhibit NMBA-induced esophageal tumorigenesis by 31-64% when
      administered in the diet following treatment of the animals with NMBA. Berries,
      therefore, inhibit tumor promotion and progression events as well as tumor
      initiation. In vivo mechanistic studies with BRBs indicate that they reduce the
      growth rate of premalignant esophageal cells, in part, through down-regulation of
      cyclooxygenase-2 leading to reduced prostaglandin production and of inducible
      nitric oxide synthase leading to reduced nitrate/nitrite levels in the esophagus.
      Based upon the preclinical data on rodents, we have initiated prevention trials
      in humans to determine if berries might exhibit chemopreventive effects in the
      esophagus.

PMID- 16800772
TI  - Modulation of N-nitrosomethylbenzylamine metabolism by black raspberries in the
      esophagus and liver of Fischer 344 rats.
AB  - Dietary freeze-dried black raspberries (BRBs) inhibit N-nitrosomethylbenzylamine
      (NMBA)-induced tumorigenesis in the Fischer 344 rat esophagus. To determine the
      mechanistic basis of the anti-initiating effects of BRBs, NMBA metabolism was
      studied in esophageal explant cultures and in liver microsomes taken from rats
      fed with AIN-76A diet or AIN-76A diet containing 5% or 10% BRBs. Five percent and
      10% dietary BRBs inhibited NMBA metabolism in explants (26% and 20%) and in
      microsomes (22% and 28%), but the inhibition was not dose dependent. To identify
      active inhibitory component(s) in BRBs, esophageal explants and liver microsomes
      from control rats were treated in vitro with an ethanol extract of BRBs or with
      individual components of BRBs [ellagic acid (EA) and two anthocyanins (cyanidin-3
      glucoside and cyanidin-3-rutinoside)]. NMBA metabolism in explants was inhibited
      maximally by cyanidin-3-rutinoside (47%) followed by EA (33%), cyanidin-3
      glucoside (23%), and the extract (11%). Similarly, in liver microsomes, the
      inhibition was maximal by cyanidin-3-rutinoside (47%) followed by EA (33%) and
      cyanidin-3-glucoside (32%). Phenylethylisothiocyanate (PEITC), a potent inhibitor
      of NMBA tumorigenesis in rat esophagus, was a stronger inhibitor of NMBA
      metabolism in vivo and in vitro than BRBs or their components. Dietary BRBs and
      PEITC induced glutathione S-transferase activity in the liver.

PMID- 16800773
TI  - Suppression of the tumorigenic phenotype in human oral squamous cell carcinoma
      cells by an ethanol extract derived from freeze-dried black raspberries.
AB  - Despite focused efforts to improve therapy, 5-yr survival rates for persons with
      advanced-stage oral squamous cell carcinoma (SCC) remain discouragingly low.
      Clearly, early detection combined with strategies for local intervention, such as
      chemoprevention prior to SCC development, could dramatically improve clinical
      outcomes. Previously conducted oral cavity human chemoprevention trials, however,
      have provided mixed results. Although some therapies showed efficacy, they were
      often accompanied by either significant toxicities or circulating antiadenoviral
      antibodies. It is clearly apparent that identification of nontoxic, effective
      treatments is essential to prevent malignant transformation of oral epithelial
      dysplasias. This study employed cell lines isolated from human oral SCC tumors to
      investigate the effects of a freeze-dried black raspberry ethanol extract (RO-ET)
      on cellular growth characteristics often associated with a transformed phenotype
      such as sustained proliferation, induction of angiogenesis, and production of
      high levels of reactive species. Our results demonstrate that RO-ET suppresses
      cell proliferation without perturbing viability, inhibits translation of the
      complete angiogenic cytokine vascular endothelial growth factor, suppresses
      nitric oxide synthase activity, and induces both apoptosis and terminal
      differentiation. These data imply that RO-ET is a promising candidate for use as
      a chemopreventive agent in persons with oral epithelial dysplasia.

PMID- 16800774
TI  - Molecular mechanisms involved in chemoprevention of black raspberry extracts:
      from transcription factors to their target genes.
AB  - Berries have attracted attention for their chemopreventive activities in last a
      few years. Dietary freeze-dried blackberries have been shown to reduce esophagus
      and colon cancer development induced by chemical carcinogen in rodents. To
      elucidate molecular mechanisms involved in chemoprevention by berry extracts, we
      employed mouse epidermal Cl 41 cell line, a well-characterized in vitro model in
      tumor promotion studies. Pretreatment of Cl 41 cells with methanol-extracted
      blackberry fraction RO-ME resulted in a dramatical inhibition of B(a)PDE-induced
      activation of AP-1 and NFkB, and expression of VEGF and COX-2. The inhibitory
      effects of RO-ME on B(a)PDE-induced activation of AP-1 and NFkappaB appear to be
      mediated via inhibition of MAPKs and IkappaBalpha phosphorylation, respectively.
      In view of the important roles of AP-1, NFkappaB, VEGF and COX-2 in tumor
      promotion/progression, and VEGF and COX-2 are target of AP-1 and NFkappaB, we
      anticipate that the ability of black raspberries to inhibit tumor development may
      be mediated by impairing signal transduction pathways leading to activation of AP
      1 and NFkappaB, subsequently resulting in down-regulation of VEGF and COX-2
      expression. The RO-ME fraction appears to be the major fraction responsible for
      the inhibitory activity of black raspberries.

PMID- 16800775
TI  - Ellagic acid and natural sources of ellagitannins as possible chemopreventive
      agents against intestinal tumorigenesis in the Min mouse.
AB  - Ellagic acid has been shown to have chemopreventive effects in various
      experimental cancer models. We wanted to see whether pure ellagic acid and
      natural ellagitannins from cloudberry (Rubus chamaemorus) seed and pulp have any
      effect on adenoma formation in Apc-mutated Min mice. From the age of 5 wk, the
      mice were fed either a control diet, a diet containing pure ellagic acid at 1,564
      mg/kg, or diets containing 4.7% (wt/wt) cloudberry seeds or 5.3% cloudberry pulp.
      The concentrations of ellagitannins and free ellagic acid in the seed diet were
      807 and 42 mg/kg and in the pulp diet 820 and 34 mg/kg, respectively. After the
      10-wk feeding period, ellagic acid had no effect on the number or size of
      adenomas in the distal or total small intestine, but it increased adenoma size in
      the duodenum when compared with the control diet (1.50+/-0.29 vs. 1.16+/-0.31 mm;
      P=0.029). Neither cloudberry seed nor pulp diets had any effect on the adenoma
      formation. Chemopreventive effects and mechanisms of whole cloudberry and other
      similar sources of phenolic compounds should, however, be studied, further taking
      into account food matrix and interactions with other dietary constituents that
      may be involved in the bioavailability and metabolism of ellagitannins.

PMID- 16800776
TI  - Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats.
AB  - The aim of the present study was to investigate the chemoprotective activity of
      anthocyanin-rich extracts (AREs) from bilberry (Vaccinium myrtillus L.),
      chokeberry (Aronia meloncarpa E.), and grape (Vitis vinifera) by assessing
      multiple biomarkers of colon cancer in male rats treated with a colon carcinogen,
      azoxymethane. Fischer 344 male rats were fed the AIN-93 diet (control) or AIN-93
      diet supplemented with AREs for 14 wk. Biomarkers that were evaluated included
      the number and multiplicity of colonic aberrant crypt foci (ACF), colonic cell
      proliferation, urinary levels of oxidative DNA damage, and expression of
      cyclooxygenase (COX) genes. To assess the bioavailability, levels of anthocyanins
      in serum, urine, and feces were evaluated. Total ACF were reduced (P<0.05) in
      bilberry, chokeberry, and grape diet groups compared with the control group. The
      number of large ACF was also reduced (P<0.05) in bilberry and chokeberry ARE-fed
      rats. Colonic cellular proliferation was decreased in rats fed bilberry ARE and
      chokeberry ARE diets. Rats fed bilberry and grape ARE diets had lower COX-2 mRNA
      expression of gene. High levels of fecal anthocyanins and increased fecal mass
      and fecal moisture occurred in ARE-fed rats. There was also a significant
      reduction (P<0.05) in fecal bile acids in ARE-fed rats. The levels of urinary 8
      hydroxyguanosine were similar among rats fed different diets. These results
      support our previous in vitro studies suggesting a protective role of AREs in
      colon carcinogenesis and indicate multiple mechanisms of action.

PMID- 16800777
TI  - Bilberry extracts induce gene expression through the electrophile response
      element.
AB  - A number of genes important for detoxification and antioxidant defense induced by
      mild stress generated by, for example, physical activity/exercise, caloric
      restriction, or alcohol may provide health benefits by causing the organism to
      mount such a defense response. More recently, induction of these defenses has
      also been attributed to phytochemicals or secondary metabolites from dietary
      plants. Many polyphenols, which constitute a large fraction of these
      phytochemicals, increase cellular levels of antioxidants, such as glutathione and
      other components of the detoxification systems, via the transactivation of genes
      containing electrophile response elements (EpREs) within their promoters. One
      such gene, gamma-glutamylcysteine synthetase, has previously been shown to be
      positively regulated by quercetin, a flavonoid found in high concentrations in
      onions, apples, and bilberries through EpRE transactivation. As a further step,
      we have investigated whether bilberries and quercetin have the ability to induce
      transcription of Fos-related antigen 1 (Fra-1), which contains two EpREs in its
      promoter. Fra-1 is a member of the activator protein 1 (AP-1) family of
      transcription factors and, due to the lack of transactivation domain Fra-1, can
      suppress activation of AP-1. We present results demonstrating that extracts from
      bilberries, and the flavonoid quercetin, abundant in bilberries, induce the fra-1
      promoter and the cellular content of Fra-1 mRNA. We further provide evidence that
      this induction is mediated through EpREs.

PMID- 16800778
TI  - Dietary modulation of the multistage, multimechanisms of human carcinogenesis:
      effects on initiated stem cells and cell-cell communication.
AB  - Diet can influence the risk to cancer in both negative and positive ways.
      Worldwide, more than 10 million persons develop cancer annually. Diet could
      prevent many cancers. Carcinogenesis is a multistage, multimechanism process,
      consisting of "initiation," "promotion," and "progression" phases. Although diet
      could affect each phase, an efficacious strategy for dietary chemoprevention
      would be intervention during the promotion phase. The tumor-promotion process
      requires sustained exposure to agents that stimulate the growth and inhibition of
      apoptosis of initiated cells in the absence of antipromoters. Chronic
      inflammation has been associated with the promotion process. The mechanism
      affecting the promotion process appears to be the inhibition of cell-cell
      communication between normal and initiated cells. Most, if not all, tumor
      promoting agents and conditions, reversibly, inhibit cell-cell communication,
      whereas antipromoters, antioxidants, and anti-inflammatory agents have been shown
      to ameliorate the effects of tumor promoters on cell-cell communication.
      Additionally, adult stem cells are hypothesized to be the target cells for
      initiating the carcinogenic process. A new paradigm has been presented that
      postulates the first function of the carcinogenic process is to block the
      "mortalization" of a normal, "immortal" adult stem cell rather than the induction
      of "immortalization" of a normal mortal cell.

PMID- 16800779
TI  - Fruit and vegetables in cancer prevention.
AB  - Our aim was to review the epidemiological literature on possible cancer
      preventive effects of the consumption of fruits and vegetables in humans, to
      quantify the effect of high versus low consumption of fruits and vegetables, and
      to give an overall assessment of the existing evidence. We based our work on an
      expert meeting conducted by the International Agency for Research on Cancer in
      2003. A qualitative reading and evaluation of relevant articles on the cancer
      preventive effect of the consumption of fruits and vegetables was made followed
      by the calculation of the mean relative risk and range for cohort and case
      control studies separately. The possible population-preventable fraction for
      modifying diet in relation to fruit and vegetable consumption was calculated as
      well as an overall statement about the degree of evidence for the cancer
      preventive effect of fruit and vegetable consumption for each cancer site. There
      is limited evidence for a cancer-preventive effect of the consumption of fruits
      and vegetables for cancer of the mouth and pharynx, esophagus, stomach, colon
      rectum, larynx, lung, ovary (vegetables only), bladder (fruit only), and kidney.
      There is inadequate evidence for a cancer-preventive effect of the consumption of
      fruits and vegetables for all other sites. Applying this range of risk difference
      to the range of prevalence of low intake, the preventable fraction for low fruit
      and vegetable intake would fall into the range of 5-12%. It is important to
      recognize that this is only a crude range of estimates and that the proportion of
      cancers that might be preventable by increasing fruit and vegetable intake may
      vary beyond this range for specific cancer sites and across different regions of
      the world.

PMID- 16800780
TI  - Markers of oxidative DNA damage in human interventions with fruit and berries.
AB  - Diets rich in fruit and vegetables are associated with a decreased risk of
      several cancers via numerous possible mechanisms. For example, phytochemicals may
      decrease oxidative DNA damage and enhance DNA repair. Markers of oxidative DNA
      damage in human dietary intervention trials used most frequently include oxidized
      nucleosides such as 7-hydro-8-oxo-2'-deoxyguanosine, which can be analyzed from
      isolated DNA or urine. Single-cell gel electrophoresis has been widely used to
      measure baseline or H2O2-induced DNA strand breaks or sites of modified bases
      sensitive to repair enzymes recognizing oxidized purines or pyrimidines.
      Recently, markers of DNA repair also have been used. Few controlled human dietary
      interventions have investigated the specific effects of fruit or berries. There
      are indications that kiwifruit can decrease H2O2 sensitivity of lymphocyte DNA ex
      vivo and enhance DNA repair. Carefully controlled studies with flavonoid-rich
      fruit or berry juices found only few significant differences; less rigorously
      controlled studies gave more optimistic results. Data on the effects of fruit and
      berries on DNA damage in humans are scarce and inconclusive; adequately
      controlled studies with validated markers are needed. Because levels of DNA
      damage are usually low in young healthy volunteers, groups with an enhanced risk
      of DNA damage should be studied.

PMID- 16800781
TI  - Transitioning from preclinical to clinical chemopreventive assessments of
      lyophilized black raspberries: interim results show berries modulate markers of
      oxidative stress in Barrett's esophagus patients.
AB  - Increased fruit and vegetable consumption is associated with decreased risk of a
      number of cancers of epithelial origin, including esophageal cancer. Dietary
      administration of lyophilized black raspberries (LBRs) has significantly
      inhibited chemically induced oral, esophageal, and colon carcinogenesis in animal
      models. Likewise, berry extracts added to cell cultures significantly inhibited
      cancer-associated processes. Positive results in preclinical studies have
      supported further investigation of berries and berry extracts in high-risk human
      cohorts, including patients with existing premalignancy or patients at risk for
      cancer recurrence. We are currently conducting a 6-mo chemopreventive pilot study
      administering 32 or 45 g (female and male, respectively) of LBRs to patients with
      Barrett's esophagus (BE), a premalignant esophageal condition in which the normal
      stratified squamous epithelium changes to a metaplastic columnar-lined
      epithelium. BE's importance lies in the fact that it confers a 30- to 40-fold
      increased risk for the development of esophageal adenocarcinoma, a rapidly
      increasing and extremely deadly malignancy. This is a report on interim findings
      from 10 patients. To date, the results support that daily consumption of LBRs
      promotes reductions in the urinary excretion of two markers of oxidative stress,
      8-epi-prostaglandin F2alpha (8-Iso-PGF2) and, to a lesser more-variable extent, 8
      hydroxy-2'-deoxyguanosine (8-OHdG), among patients with BE.

PMID- 16800782
TI  - A novel gene of beta chain of the IFN-gamma receptor of Huiyang chicken: cloning,
      distribution, and CD assay.
AB  - The beta chain of the interferon-gamma receptor (IFNGR-2) plays a critical role
      in signal transmission to the nucleus by IFN-gamma. Here, we cloned the full
      length cDNA of IFNGR-2 of Huiyang chicken using RACE. mRNA transcripts of IFNGR-2
      were detected in peripheral blood leukocytes (PBL) and various organs using
      Northern blot analysis. The extracellular region of IFNGR-2 (IFNGR-2EC) was
      expressed in Pichia pastoris, and its secondary structure was investigated by
      circular dichroism (CD). The Huiyang chicken IFNGR-2 gene is 2221 bp with a
      polyA+ tail, and it encodes 334 amino acids sharing 30%-33% identity with that of
      rat, mouse, and human IFNGR-2. IFNGR-2 is localized on chromosome 1 of chicken in
      tandem with IFNAR-1, interleukin- 10 receptor (IL-10R-2), and IFNAR-2. IFNGR-2
      was highly expressed in PBL, muscle, spleen, thymus, and cecal tonsil, whereas
      its expression in cardiac muscle, cloacal bursa, liver, and kidney was
      comparatively low. Recombinant protein of IFNGR-2EC expressed in P. pastoris
      formed the secondary structure including 19.8% alpha-helix, 29.6% beta-sheet,
      19.7% turn, and 30.9% random. The data show that Huiyang chicken IFNGR-2 shares
      properties of the IFN receptor family in gene structure and distribution in
      multiple tissues and PBL. CD analysis indicated that the recombinant protein of
      IFNGR-2EC resembles the known structure of human IFN receptors.

PMID- 16800783
TI  - Gene-based delivery of IFN-beta is efficacious in a murine model of experimental
      allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is a model of central nervous
      system (CNS) inflammation that follows immunization with certain CNS antigens.
      The course and clinical manifestations of EAE are similar to those of multiple
      sclerosis (MS) in humans; therefore, EAE has become an accepted animal model to
      study MS. The purpose of this study was to demonstrate that systemic expression
      of murine interferon-beta (IFN-beta) (MuIFN-beta), following intramuscular (i.m.)
      delivery of plasmid DNA encoding MuIFN-beta to the hind limb of mice, is
      effective in reducing the clinical manifestations of disease in a model of EAE.
      The results of the study demonstrate that gene-based delivery of MuIFN-beta
      caused significantly decreased clinical scores compared with delivery of the null
      vector. A single injection of the MuIFN-beta plasmid was as effective in reducing
      the severity of the disease as an every other day injection of MuIFN-beta
      protein.

PMID- 16800784
TI  - The human papillomavirus type 16 E7 protein binds human interferon regulatory
      factor-9 via a novel PEST domain required for transformation.
AB  - It is critical that viruses are able to avoid the antiviral activities of
      interferon (IFN). We have shown previously that the human papillomavirus (HPV) is
      able to avoid IFN-alpha via interaction of the HPV-16 E7 protein with IFN
      regulatory factor-9 (IRF-9). Here, we investigated the details of the interaction
      using HPV-16 E7 peptide mapping to show that IRF-9 binds HPV-16 E7 in a domain
      encompassing amino acids 25-36. A closer examination of this region indicates
      this is a novel proline, glutamate, serine, and threonine-rich (PEST) domain,
      with a PEST score of 8.74. We have also mapped the region of interaction within
      IRF-9 and found that amino acids 354-393 play an important role in binding to HPV
      16 E7. This region of IRF-9 encompasses the IRF association domain (IAD), a
      region important for protein-protein interaction central to IRF function.
      Finally, we used alanine-scanning mutagenesis to determine if E7-IRF-9
      interaction was important for E7-mediated cellular transformation and found that
      the HPV-16 E7 mutants Y25A, E26A, S31A, S32A, and E35A, but not L28A and N29A,
      caused loss of transformation ability. Preliminary data suggest loss of IRF-9
      interaction with E7 mutants correlated with transformation. Our work suggests E7
      IRF-9 interaction is important for the transforming ability of HPV-16 E7 and that
      HPV-16 E7 may interact with other IRF proteins that have IAD domains.

PMID- 16800785
TI  - Differential gene induction by type I and type II interferons and their
      combination.
AB  - Type I and type II interferons (IFNs) bind to different cell surface receptors
      but activate overlapping signal transduction pathways. We examined the effects of
      a type I IFN (IFN-alphacon1) and a type II IFN (IFN-gamma1b) on gene expression
      in A549 cells and demonstrate that there is a common set of genes modulated by
      both IFNs as well as a set of genes specifically regulated by each, reflecting
      the activation of different signaling pathways. In particular, IFN-gamma induced
      many more genes of the signaling pathways, apoptosis, and cytokine interactions
      than did IFN-alpha. Even with genes induced by both IFNs there were distinctive
      quantitative differences in expression. IFN-gamma1b plays a major role in the
      induction and regulation of the complement pathway. Previous work has shown a
      synergistic antiviral and antiproliferative effect of type I and type II IFNs in
      cell culture and in the treatment of tumors in mice. We demonstrate that a
      majority of genes showed an additive effect of IFN-alphacon1 and IFN-gamma1b, but
      a subset of genes is synergistically induced; these include ISG20, MX2, OAS2, and
      other genes known to be involved in the antiviral response, TRAIL (TNFSF10) and
      caspases involved in apoptosis and chemokine genes RANTES, CXCL10, and CXCL11.
      Greater than additive transcription of some of these genes in the presence of
      both IFNs was confirmed by real-time kinetic RT-PCR. Elevated induction of many
      of these genes may be sufficient to explain the synergistic antiviral and
      antitumor effects of this combination of IFNs in vivo.

PMID- 16800786
TI  - Immunomodulatory activities of IFN-gamma1b in combination with type I IFN:
      implications for the use of IFN-gamma1b in the treatment of chronic HCV
      infections.
AB  - The standard of care for chronic hepatitis C, pegylated interferon-alpha (IFN
      alpha) and ribavirin (RBV), causes a sustained virologic response (SVR) in
      approximately 50% of patients. SVR is correlated with innate and adaptive immune
      system responses, such as natural killer (NK) cell activation, production of IFN
      alpha from immature plasmocytoid dendritic cells (pDC), and polarization of
      CD4(+) cells to a T helper 1 (Th1) cell phenotype. To examine how these
      immunologic responses vary with currently available regimens for chronic
      hepatitis C, cell populations purified from human peripheral blood mononuclear
      cells (PBMC) were treated with the clinically available combinations of pegylated
      IFN-alpha2b (PEG-IFN-alpha2b) + RBV, IFN-alphacon1 + RBV, or IFN- alphacon1 + IFN
      gamma1b, and activation of cellular immune system components was monitored. The
      magnitude of NK cell activation depended on regimen, with IFN-alphacon1 + IFN
      gamma1b > IFN-alphacon1 + RBV > PEG-IFN- alphaa2b + RBV. The maximum human serum
      concentrations of IFN-alphacon1 + IFN-gamma1b saturated NK cell activation,
      whereas the maximum human serum concentrations of IFN-alphacon1 + RBV or PEG-IFN
      alpha2b + RBV did not. IFN-gamma1b also enhanced the production of IFN-alpha from
      immature pDCs, which are the dominant source of IFN-alpha upon viral infection.
      The rank order for induction of Th1 cell phenotype and repression of Th2 cell
      phenotype by the cocktails described was identical to that observed for NK cell
      activation. Additionally, IFN- gamma1b suppressed the ability of the hepatitis C
      virus (HCV) NS4 protein to enhance monocyte secretion of interleukin- 10 (IL-10),
      a cytokine whose expression level is correlated with viral persistence. These
      results suggest that addition of IFN-gamma1b to HCV treatment regimens may
      provide unique benefits.

PMID- 16800787
TI  - Diagnostic accuracy of ascitic fluid IFN-gamma and adenosine deaminase assays in
      the diagnosis of tuberculous ascites.
AB  - In this study, we evaluated the diagnostic accuracy and cost-effectiveness of
      ascitic fluid interferon-gamma (IFN-gamma) and adenosine deaminase (ADA) assays
      in the diagnosis of tuberculous ascites. Ascitic fluid from patients with proven
      tuberculosis (TB) (n = 31) and non-TB ascites (n = 88) was analyzed for IFN-gamma
      and ADA levels. Areas under the receiver operative characteristic (ROC) curves
      (AUCs) for the two biologic markers were compared. Levels of ascitic fluid IFN
      gamma, median (range): 560 (104-1600) pg/mL vs. 4.85 (0-320) pg/mL (p < 0.001),
      and ADA, median (range): 58 (16-331) IU/L vs. 10 (0-59) IU/L (p = 0.001), were
      significantly different between TB and non-TB groups. IFN-gamma and ADA assays
      showed equal sensitivity (0.97) and differed marginally in specificity (0.97 vs.
      0.94). Difference in AUCs was not significant (0.99 vs. 0.98, p < 0.62). For
      differentiating TB from non-TB ascites, optimal cutoff points were 112 pg/mL for
      IFN-gamma and 37 IU/L for ADA. The accuracy of the ADA assay was similar to that
      of the IFN-gamma assay in differentiating of TB from non-TB ascites. Because both
      material and human costs of the ADA assay are far less than those of the IFN
      gamma assay, the former is probably the most appropriate diagnostic test for
      analysis of peritoneal fluid in resource- limited settings.

PMID- 16800788
TI  - Oral administration of lactoferrin increases NK cell activity in mice via
      increased production of IL-18 and type I IFN in the small intestine.
AB  - Evidence that lactoferrin (LF) influences various immune functions is now
      accumulating. Recent reports have shown that bovine LF (BoLF) enhances
      antimicrobial, antiviral, and antitumor immune activities when orally
      administered. Here, we report that orally administered BoLF increases natural
      killer (NK) cell populations in peripheral blood and spleen in a dose-dependent
      manner and enhances interferon-gamma (IFN-gamma) production by NK cells. Using
      intraperitoneal (i.p.) injection of poly(I:C) to induce NK cell trafficking into
      the peritoneum, oral BoLF increased NK cell migration. Oral BoLF also produced an
      immediate increase in the levels of interleukin-18 (IL-18) in the portal
      circulation. In IL-18 knockout (KO) mice, BoLF did not increase the numbers of NK
      cells, although NK cell cytotoxic activity and poly(I:C)-induced trafficking
      activity were both enhanced by oral BoLF, even in IL-18 KO mice. Furthermore,
      oral BoLF increased the expression of IFN-alpha and IFN-beta in Peyer's patches
      (PP) and mesenteric lymph nodes (MLN). Oral administration of 2- chloroadenosine
      selectively depleted the PP cells and blocked the ability of oral BoLF to
      increase NK cell accumulation in the peritoneum following poly(I:C) i.p.
      injection. Collectively, these results demonstrate that orally administered BoLF
      stimulates intestine-associated immune functions, including the production of IL-
      18 and type I IFNs and increased NK cell activity.

PMID- 16800792
TI  - Recent advances in protein and peptide chemistry related to cellular regulation.

PMID- 16800793
TI  - In vitro folding/unfolding of insulin/single-chain insulin.
AB  - Insulin is a double-chain (designated A and B chain respectively) protein hormone
      containing three disulfides, while insulin is synthesized in vivo as a single
      chain precursor and folded well before being released from B-cells. Although the
      structure and function of insulin have been well characterized, the progress in
      oxidative folding pathway studies of insulin has been very slow, mainly due to
      the difficulties brought about by its disulfide-linked double-chain structure. To
      overcome these difficulties, we recently studied the in vitro oxidative folding
      process of two single-chain insulins: porcine insulin precursor (PIP) and human
      proinsulin (HPI). Based on the analysis of the intermediates captured during
      folding process, the folding pathways have been proposed for PIP and HPI
      separately. Similarities between the two folding pathways disclose some common
      principles that govern the insulin folding process. The following unfolding
      studies of PIP and HPI further indicate that C-peptide might also function during
      the folding of proinsulin. Here, we gave a brief review on in vitro
      folding/unfolding process of insulin and single-chain insulin. The implication of
      these studies on protein folding has also been discussed.

PMID- 16800794
TI  - Increased solubility of integrin betaA domain using maltose-binding protein as a
      fusion tag.
AB  - In proteomics research, generation of recombinant proteins in their native,
      soluble form with large quantity is often a challenging task. To tackle the
      expression difficulties, different expression vectors with distinct affinity
      fusion tags, i.e. pET-43.1a (N-utilization substance A tag), pMAL-cRI (maltose
      binding protein tag) (MBP tag), pGEX-4T-2 (glutathione S-transferase tag), and
      pET-15b (hexahistidine tag) were compared for their effects on the productivity
      and solubility, which were assessed by SDS-PAGE and immunoblotting, of the
      integrin betaA domain. The incubation temperatures were tested for its effects on
      these parameters. Our data suggested that MBP tag enhanced the yield and
      solubility of the betaA domain protein, which can also be recognized using an
      anti-CD18 antibody, at room temperature incubation. Thus, the nature of fusion
      partner chosen for expression in bacteria and its incubation temperature would
      significantly affect the yield and solubility of the recombinant target protein.

PMID- 16800795
TI  - Opioid receptor-like (ORL1) receptor utilizes both G(oA) and G(oB) for signal
      transduction.
AB  - The ORL1 receptors stably expressed in HEK 293 cells can utilize PTX-resistant
      mutants of Galpha(oA/B) to inhibit adenylyl cyclase (AC) and stimulate
      extracellular signal-regulated protein kinases (ERKs). However, development of AC
      superactivation and loss of ERK1/2 responsiveness induced by chronic activation
      of the ORL1 receptors remained PTX-sensitive.

PMID- 16800796
TI  - Identification of histidine-60 interaction with copper in activation of
      Chironomidae ferrochelatase.
AB  - Site-directed mutagenesis study of the conserved residue in ferrochelatase of
      chironomidae showed the binding interaction of copper with histidine-60. The
      activities of the variants increase by > 4-fold with H60N and 2 fold with H60D.
      The study identifies for the first time that the highly conserved H60 is a key
      molecular determinant in directing a catalytically competent mode of metal
      binding in the active site.

PMID- 16800797
TI  - Structure and function of bovine pancreatic deoxyribonuclease I.
AB  - Bovine pancreatic deoxyribonuclease I (bpDNase), the first DNase discovered, is
      the best characterized among various types of DNase. A catalytic mechanism has
      been suggested based on the X-ray structure of the bpDNase-octamer complex. In
      this review, we will focus on three aspects: 1) the distinctive functions of the
      two structural calcium atoms; 2) the biological functions of the two disulfides;
      and 3) the involvement of the N- and C-terminal fragments in the enzyme folding
      for activity.

PMID- 16800799
TI  - Deciphering signaling control by phosphoproteome using mass spectrometry.
AB  - Analysis of changes in genes and protein profiles provides invaluable information
      to understand the activities and functions of proteins. However, their activities
      are further regulated by post-translational modifications, such as glycosylation
      and phosphorylation. Cell growth and apoptotic pathways are good examples of
      demonstrating the roles of phosphorylation in activation of protein cascades upon
      stimulation.

PMID- 16800798
TI  - Protein-peptide interaction studies demonstrate the versatility of calmodulin
      target protein binding.
AB  - Calmodulin (CaM) is a prototypical Ca2+-sensor protein that can control many
      important biological functions by binding to hundreds of target proteins. To gain
      insight into the versatility of CaM-target recognition, we have analyzed the
      complex structures for many types of CaM-binding peptides and some target
      proteins. In particular, some recently reported novel complex structures reveal
      that the versatile target binding of CaM is accommodated by its flexible domain
      arrangement and the malleability of its interfaces.

PMID- 16800800
TI  - Structure formation in short designed peptides probed by proteolytic cleavage.
AB  - The formation of local structure, in short peptides has been probed by examining
      cleavage patterns and rates of proteolysis of designed sequences with a high
      tendency to form beta-hairpin structures. Three model sequences which bear
      fluorescence donor and acceptor groups have been investigated: [see text].
      Fluorescence resonance energy transfer (FRET) provides a convenient probe for
      peptide cleavage. MALDI mass spectrometry has been used to probe sites of
      cleavage and CD spectroscopy to access the overall backbone conformation using
      analog sequences, which lack strongly absorbing donor and acceptor groups. The
      proteases trypsin, subtilisin, collagenase, elastase, proteinase K and
      thermolysin were used for proteolysis and the rates of cleavage determined.
      Peptide 3 is the most susceptible to cleavage by all the enzymes except
      thermolysin, which cleaves all three peptides at comparable rates. Peptides 1 and
      2 are completely resistant to the action of trypsin, suggesting that beta-turn
      formation acts as a deterrent to proteolytic cleavage.

PMID- 16800801
TI  - Thermostability of the HIV gp41 wild-type and loop mutations.
AB  - The HIV and SIV gp41 ectodomains are extremely stable to chemical and thermal
      denaturation and the observed stability has been proposed to be an important
      thermodynamic driving force for gp41-mediated fusion of the viral and target cell
      membranes. The importance of the disulphide bond and surrounding residues within
      the HIV gp41 loop have been assayed by DSC studies of wild type and mutant HIV
      gp41. Based on the thermal transition temperature, the disulphide bond and
      surrounding residues do not contribute to the thermal stability of gp41 and thus
      do not contribute to gp41-mediated membrane fusion.

PMID- 16800802
TI  - Proteome analysis of resting human neutrophils.
AB  - Neutrophils constitute the first line of host defense against pathogens. In the
      present study 2-D gel electrophoresis-mass spectrometry technology was employed
      to analyze the human resting neutrophils proteome. One hundred and two conserved
      spots were subjected to peptide mass fingerprinting, yielding 22 identifications.
      Among the identified proteins, nine are related to the inflammatory process, two
      polypeptides are assigned to metabolic functions and five are classified as
      structural.

PMID- 16800803
TI  - Predicting protein structural class with AdaBoost Learner.
AB  - The structural class is an important feature in characterizing the overall
      topological folding type of a protein or the domains therein. Prediction of
      protein structural classification has attracted the attention and efforts from
      many investigators. In this paper a novel predictor, the AdaBoost Learner, was
      introduced to deal with this problem. The essence of the AdaBoost Learner is that
      a combination of many 'weak' learning algorithms, each performing just slightly
      better than a random guessing algorithm, will generate a 'strong' learning
      algorithm. Demonstration thru jackknife cross-validation on two working datasets
      constructed by previous investigators indicated that AdaBoost outperformed other
      predictors such as SVM (support vector machine), a powerful algorithm widely used
      in biological literatures. It has not escaped our notice that AdaBoost may hold a
      high potential for improving the quality in predicting the other protein features
      as well, such as subcellular location and receptor type, among many others. Or at
      the very least, it will play a complementary role to many of the existing
      algorithms in this regard.

PMID- 16800804
TI  - Synthesis of peptidyl ureas employing O-succinimidyl-(9H-fluoren-9
      ylmethoxycarbonylamino) methylcarbamate derivatives as activated monomers.
AB  - A convenient and efficient method for the synthesis of dipeptidyl ureas and urea
      acids employing O-succinimidyl-(9H-fluoren-9-ylmethoxycarbonyl
      amino)methylcarbamates has been described. All the compounds, obtained in good
      yields, have been fully characterized by mass and NMR spectra.

PMID- 16800805
TI  - Design and synthesis of novel chemokine analogs derived from vMIP-II.
AB  - Stepwise solid phase synthesis using the Fmoc chemistry is reported for a panel
      of 71-residue and novel unnatural chemokine analogs derived from vMIP-II. This
      demonstrates the feasibility of using this synthetic method to generate de novo
      designed protein ligand molecules to study the biology and pharmacology of
      chemokine receptors.

PMID- 16800806
TI  - Important contributions of a new quantitative preparative native continuous
      polyacrylamide gel electrophoresis (QPNC-PAGE) procedure for elucidating metal
      cofactor metabolisms in protein-misfolding diseases--a theory.
AB  - The quantitative analysis of metallochaperone proteins in biofluids (e.g. blood,
      liquor) may be a major prerequisite for clinical investigations concerning the
      structure-function relationships of biologically-active metal cofactor-containing
      chaperones in protein-misfolding diseases (e.g. Alzheimer's or related diseases).
      For these purposes, a new state-of-the-art gel electrophoresis [quantitative
      preparative native continuous polyacrylamide gel electrophoresis procedure (QPNC
      PAGE)] combined with biological mass and NMR spectrometries might essentially
      contribute to provide fundamental insights into the metabolisms of important
      metal cofactors in biological systems and the proper folding of metallochaperones
      in conformational diseases.

PMID- 16800807
TI  - N-terminus leader sequence of Shiga toxin (Stx) 1 is essential for production of
      active recombinant protein in E. coli.
AB  - Escherichia coli clones expressing recombinant shiga toxin (Stx1) and its
      derivatives Stx1-A and Stx1-B subunits were established to release the proteins
      into periplasmic space. The expression was examined by SDS-PAGE to visualize the
      subunits. The secreted assembled subunits were extracted with polymyxin B and
      assessed for biological activity. The results showed that the presence of N
      terminus leader sequence of the gene is essential for assembly of the subunits to
      yield biologically active holotoxin (AB5). The absence of the leader sequence did
      not affect the expression of the subunits but did disrupt the holotoxin assembly.

PMID- 16800808
TI  - A periplasmic glutamate/aspartate binding protein from Shigella flexneri: Gene
      cloning, over-expression, purification and preliminary crystallographic studies
      of the recombinant protein.
AB  - Periplasmic substrate binding proteins (PSBPs) are essential components of the
      bacterial periplasmic transport system, which transports a wide variety of
      nutrients from the periplasmic space to the cytoplasm. The glutamate/aspartate
      binding protein SfGlu/AspBP is a unique PSBP consisting of 279 amino acid
      residues. The SfGlu/AspBP gene was cloned, over-expressed, and purified by
      immobilized metal ion affinity chromatography and size-exclusion chromatography.
      The recombinant protein SfGlu/AspBP has been crystallized by the hanging-drop
      vapor-diffusion method and its X-ray diffraction data were collected at an atomic
      resolution of 1.15 A. The crystals belong to the space group P2(1) with unit cell
      parameters: a = 48.41 A, b = 68.18 A, c = 80.21 A and beta = 98.78 degrees. There
      are two molecules per asymmetric unit.

PMID- 16800809
TI  - Rattlesnake hemoglobins: Functional properties and tetrameric stability.
AB  - The present work analyzed the tetrameric stability of the hemoglobins from the
      rattlesnake C. durissus terrificus using analytical gel filtration
      chromatography, SAXS and osmotic stress. We show that the dissociation mechanism
      proposed for L. miliaris hemoglobin does not apply for these hemoglobins, which
      constitute stable tetramers even at low concentrations.

PMID- 16800810
TI  - Contribution of halophilic nucleoside diphosphate kinase sequence to the heat
      stability of chimeric molecule.
AB  - A halophilic nucleoside diphosphate kinase from a moderate halophile, Halomonas
      sp. 593 (593NDK), was found to be resistant to heat treatment, as indicated by
      the high level of activity recovery after heating at high temperatures. This is
      due to reversibility of thermal unfolding, not the high melting temperature, of
      the protein. The highly homologous NDK from non-halophilic organism, Pseudomonas
      aeruginosa, showed instability against heat treatment. Chimeric molecules
      consisting of each half of these two NDKs were constructed and characterized for
      their heat stability. The results showed that the N-terminal half of 593NDK
      contributes to the heat stability of the proteins. We discuss the possible reason
      for the observed difference in resistance to heat treatment between the 593NDK
      and PaNDK and between two chimeric proteins.

PMID- 16800811
TI  - Crystallization and preliminary X-ray studies of the DNA-binding domain of
      hepatocyte nuclear factor-6alpha complexed with DNA.
AB  - Hepatocyte nuclear factor 6 (HNF-6)/OC-1, a part of liver-enriched transcription
      factor, controls pancreas and liver development and regulates expression of
      several hepatic genes. DNA-binding region of HNF-6alpha bound to a 14-mer DNA
      fragment has been crystallized by the hanging drop vapor diffusion method. The
      crystals belong to space group P2 with unit cell parameters of a = 73.0 A, b =
      39.0 A, c = 106.5 A, beta = 107.6 degrees. X-ray diffraction data were collected
      to 2.0 A resolution.

PMID- 16800813
TI  - A macrokinetic model for myeloma cell culture based on stoichiometric balance.
AB  - A macrokinetic model for a myeloma cell line is proposed. The model describes the
      dynamic balances of lactate, alanine, ATP and NADH during the metabolsim of
      glucose, glutamine and other amino acids. The metabolic pathways mainly include
      glycolysis, glutaminolysis, the trcicarboxylic acid cycle, the formation and
      utilization of amino acids, the respiratory chain, cell growth and cell death.
      The metabolic shift of glucose is especially considered because of a change in
      the rate of glycolysis. Thus the model functions in three modes to describe the
      behaviour of the myeloma cell line. On the basis of this model the macrokinetic
      bioreaction rates such as the specific substrate consumption rate, the specific
      growth rate, the specific acetyl-CoA formation rate, as well as the specific
      oxygen uptake rate, are estimated. The specific substrate consumption rate and
      the specific growth rate are then coupled into a bioreactor model such that the
      key variables, i.e., the cell density, the substrate and metabolite
      concentrations, are obtained. Experiments with batch and fed-batch cultures of a
      myeloma cell line (X63-Ag8.653) were used to validate the model. The prediction
      of the model was simulated by the rolling prediction approach.

PMID- 16800812
TI  - Chinese-scorpion (Buthus martensi Karsch) toxin BmK alphaIV, a novel modulator of
      sodium channels: from genomic organization to functional analysis.
AB  - In the present study, BmK alphaIV, a novel modulator of sodium channels, was
      cloned from venomous glands of the Chinese scorpion (Buthus martensi Karsch) and
      expressed successfully in Escherichia coli. The BmK alphaIV gene is composed of
      two exons separated by a 503 bp intron. The mature polypeptide contains 66 amino
      acids. BmK alphaIV has potent toxicity in mice and cockroaches. Surface-plasmon
      resonance analysis found that BmK alphaIV could bind to both rat cerebrocortical
      synaptosomes and cockroach neuronal membranes, and shared similar binding sites
      on sodium channels with classical AaH II (alpha-mammal neurotoxin from the
      scorpion Androctonus australis Hector), BmK AS (beta-like neurotoxin), BmK IT2
      (the depressant insect-selective neurotoxin) and BmK abT (transitional
      neurotoxin), but not with BmK I (alpha-like neurotoxin). Two-electrode voltage
      clamp recordings on rNav1.2 channels expressed in Xenopus laevis oocytes revealed
      that BmK alphaIV increased the peak amplitude and prolonged the inactivation
      phase of Na+ currents. The structural and pharmacological properties compared
      with those of other scorpion alpha-toxins suggests that BmK alphaIV represents a
      novel subgroup or functional hybrid of alpha-toxins and might be an evolutionary
      intermediate neurotoxin for alpha-toxins.

PMID- 16800814
TI  - RNAi-mediated silencing of prohormone convertase (PC) 5/6 expression leads to
      impairment in processing of cocaine- and amphetamine-regulated transcript (CART)
      precursor.
AB  - Understanding the functions of the widely expressed PCs (prohormone/proprotein
      convertases), including PC5/6, furin and PACE4 (paired basic amino acid cleaving
      enzyme 4), in animal models is difficult since individual knockouts of these PCs
      in mice exhibit early embryonic lethality. To investigate the roles of PC5/6 in
      processing pro-CART (pro-cocaine- and amphetamine-regulated transcript), an
      important anorexigenic peptide precursor, we have generated GH3 cells silenced
      for PC5/6 expression by RNAi (RNA interference). We show, following transient
      knockdown of PC5/6 in these neuroendocrine cells, that generation of the two
      bioactive forms, CART I (amino acids 42-89/55-102) and CART II (amino acids 49
      89/62-102), from pro-CART is impaired due to a lack particularly of the A isoform
      of PC5/6. The results indicate that PC5/6A shares specificities primarily with
      PC2 (PC5/6A<PC2) in cleaving the pairs of basic residues, KR (40, 41 //53, 54/)
      and KK (47, 48//60, 61/), within the pro-CART isoforms [see Dey, Zhu, Carroll,
      Turck, Stein and Steiner (2003) J. Biol. Chem. 278, 15007-15014]. We do not find
      any significant role of PC5/6A in processing the RXXR (29-32/) site for
      production of intermediate CART (amino acids 33-102) from long pro-CART. The
      findings taken altogether indicate that PC5/6 participates in normal processing
      of pro-CART.

PMID- 16800815
TI  - Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver
      cells.
AB  - We have investigated the mechanism of COX-2 (cyclo-oxygenase 2)-dependent
      inhibition of apoptosis in liver, a key pathway underlying proliferative actions
      of COX-2 in liver cancers, cirrhosis, chronic hepatitis C infection and
      regeneration after partial hepatectomy. Stable expression of COX-2 in CHL (Chang
      liver) cells induced proliferation, with an increase in the proportion of cells
      in S-phase, but no other significant changes in cell-cycle distribution. This was
      associated with a marked inhibition of the apoptotic response to serum
      deprivation, an effect mimicked by treating empty-vector-transfected control
      cells (CHL-V cells) with prostaglandin E2 and prevented in COX-2-expressing cells
      (CHL-C cells) treated with selective inhibitors of COX-2. Serum-deprived CHL-V
      cells displayed several indicators of activation of intrinsic apoptosis: caspases
      9 and 3 activated within 6 h and caspase 8 within 18 h, Bax expression was
      induced, cytochrome c was released to the cytosol, and PARP-1 [poly(ADP-ribose)
      polymerase 1] cleavage was evident in nuclei. COX-2 expression blocked these
      events, concomitant with reduced expression of p53 and promotion of Akt
      phosphorylation, the latter indicating activation of survival pathways. CHL cells
      were resistant to stimulation of the extrinsic pathway with anti-Fas antibody.
      Moreover, in vivo expression of GFP (green fluorescent protein)-labelled COX-2 in
      mice by hydrodynamics-based transient transfection conferred resistance to
      caspase 3 activation and apoptosis induced by stimulation of Fas.

PMID- 16800816
TI  - Recruitment of the SWI/SNF protein Brg1 by a multiprotein complex effects
      transcriptional repression in murine erythroid progenitors.
AB  - SWI/SNF complexes are involved in both activation and repression of
      transcription. While one of two homologous ATPases, Brg1 [Brm (Brahma)-related
      gene 1] or Brm, is required for their chromatin remodelling function, less is
      known about how these complexes are recruited to DNA. We recently established
      that a DNA-binding complex containing TAL1/SCL, E47, GATA-1, LMO2 and Ldb1
      stimulates P4.2 (protein 4.2) transcription in erythroid progenitors via two E
      box-GATA elements in the gene's proximal promoter. We show here that the SWI/SNF
      protein Brg1 is also associated with this complex and that both the E box and
      GATA DNA-binding sites in these elements are required for Brg1 recruitment.
      Further, Brg1 occupancy of the P4.2 promoter decreased with terminal erythroid
      differentiation in association with increased P4.2 transcription, while enforced
      expression of Brg1 in murine erythroleukaemia cells reduced P4.2 gene expression.
      Overexpression of Brg1 was associated with increased occupancy of the P4.2
      promoter by the nuclear co-repressor mSin3A and HDAC2 (histone deacetylase 2) and
      with reduced histone H3 and H4 acetylation. Finally, a specific HDAC inhibitor
      attenuated Brg1-directed repression of P4.2 promoter activity in transfected
      cells. These results provide insight into the mechanism by which SWI/SNF proteins
      are recruited to promoters and suggest that transcription of P4.2, and most
      likely other genes, is actively repressed until the terminal differentiation of
      erythroid progenitors.

PMID- 16800818
TI  - Effect of dietary antioxidants and risk of oral, pharyngeal and laryngeal
      squamous cell carcinoma according to smoking and drinking habits.
AB  - Several intervention trials and prospective studies have reported that beta
      carotene supplementation is not associated with a decreased risk of several
      cancers among smokers and drinkers, and that it may even have adverse effects in
      these groups. The relationship between dietary antioxidant intake and the risk of
      head and neck squamous cell carcinoma (HNSCC) has been examined intensively, but
      little is known about the effects of antioxidants on HNSCC with respect to
      smoking and drinking habits. Here, we conducted a case-control study of 385
      histologically confirmed cases of HNSCC (193 oral, 132 pharyngeal and 60
      laryngeal), excluding nasal and paranasal cancer, and 1925 age-matched and sex
      matched cancer-free outpatient controls using data from the Hospital-based
      Epidemiologic Research Program at Aichi Cancer Center, Japan. The intake of
      nutrients and food groups was assessed with a food frequency questionnaire, and
      multivariate-adjusted odds ratios for cancer were estimated for smoking and
      drinking habits using logistic models. The results showed an overall inverse
      association between the intake of dietary antioxidants, including carotene, and
      vitamins C and E, and risk of HNSCC. The protective effect of these antioxidants
      was seen in both men and women. High consumption of antioxidants was associated
      with a decreased risk of HNSCC among smokers, drinkers and those with both
      smoking and drinking habits. These findings suggest that dietary antioxidant
      intake prevents HNSCC in smokers and drinkers.

PMID- 16800817
TI  - Hepatocyte nuclear factor-4alpha contributes to carbohydrate-induced
      transcriptional activation of hepatic fatty acid synthase.
AB  - Refeeding a carbohydrate-rich meal after a fast produces a co-ordinated induction
      of key glycolytic and lipogenic genes in the liver. The transcriptional response
      is mediated by insulin and increased glucose oxidation, and both signals are
      necessary for optimal induction of FAS (fatty acid synthase). The glucose
      regulated component of FAS promoter activation is mediated in part by ChREBP
      [ChoRE (carbohydrate response element)-binding protein], which binds to a ChoRE
      between -7300 and -7000 base-pairs in a carbohydrate-dependent manner. Using in
      vivo footprinting with nuclei from fasted and refed rats, we identify an
      imperfect DR-1 (direct repeat-1) element between -7110 and -7090 bp that is
      protected upon carbohydrate refeeding. Electrophoretic mobility-shift assays
      establish that this DR-1 element binds HNF-4alpha (hepatocyte nuclear factor
      4alpha), and chromatin immunoprecipitation establishes that HNF-4alpha binding to
      this site is increased approx. 3-fold by glucose refeeding. HNF-4alpha
      transactivates reporter constructs containing the distal FAS promoter in a DR-1
      dependent manner, and this DR-1 is required for full glucose induction of the FAS
      promoter in primary hepatocytes. In addition, a 3-fold knockdown of hepatocyte
      HNF-4alpha by small interfering RNA produces a corresponding decrease in FAS gene
      induction by glucose. Co-immunoprecipitation experiments demonstrate a physical
      interaction between HNF-4alpha and ChREBP in primary hepatocytes, further
      supporting an important complementary role for HNF-4alpha in glucose-induced
      activation of FAS transcription. Taken together, these observations establish for
      the first time that HNF-4alpha functions in vivo through a DR-1 element in the
      distal FAS promoter to enhance gene transcription following refeeding of glucose
      to fasted rats. The findings support the broader view that HNF-4alpha is an
      integral component of the hepatic nutrient sensing system that co-ordinates
      transcriptional responses to transitions between nutritional states.

PMID- 16800819
TI  - Different susceptibility to peroxisome proliferator-induced hepatocarcinogenesis
      in rats with polymorphic glutathione transferase genes.
AB  - Although peroxisomal bifunctional enzyme (enoyl-CoA hydratase/L-3-hydroxyacyl-CoA
      dehydrogenase; BE) is a positive marker for peroxisome proliferation, it is
      completely absent or expressed very weakly in rat hepatic preneoplastic and
      neoplastic lesions induced by peroxisome proliferators (PP). After administration
      of PP for 8-15 weeks, some rats exhibit BE-negative preneoplastic foci but other
      rats do not. In the present study, to investigate the involvement of glutathione
      S-transferase (GST) M1 gene polymorphism in interindividual differences in
      susceptibility to PP, we developed a method to determine the genotypes of rats.
      We then examined whether rats with one type encoding 198Asn-199Cys (NC-type) or
      another encoding 198Lys-199Ser (KS-type) exhibit differences in clofibrate (CF)
      susceptibility. After administration of 0.3% CF for 6 weeks or more, BE-negative
      foci were found immunohistochemically in KS/KS-type rats, but not in NC/NC-type
      rats. The number of BE-negative foci in KS/KS rats was 15.3 +/- 9.0 foci/cm2 of
      liver section after 6 weeks of CF administration, and the values did not alter
      thereafter. The mean areas of BE-negative foci in KS/KS rat livers increased
      during the period from 6 to 60 weeks. At weeks 30 and 60, almost all BE-negative
      foci exhibited a clear cell phenotype, a type of preneoplastic hepatic lesion. BE
      negative foci were devoid of peroxisome proliferator-activated receptor alpha,
      whereas surrounding tissues were positive for the receptor. These results
      indicate that rats that are polymorphic for the GST M1 gene exhibit different
      susceptibilities to CF in vivo.

PMID- 16800820
TI  - ERK MAP kinase in G cell cycle progression and cancer.
AB  - The extracellular-signal-regulated kinase (ERK) mitogen-activated protein (MAP)
      kinase signaling pathway plays an important role in various cellular responses,
      including cell proliferation, cell differentiation and cell survival. Recent
      studies have identified a number of Ras/ERK signaling-related proteins, such as
      scaffold proteins and inhibitors. These proteins modulate ERK signaling and
      thereby could give variations in ERK signaling outputs that regulate cell fate
      decisions. Here we focus on the role of ERK signaling in cell cycle progression
      from G0/G1 to S phase and cancer.

PMID- 16800821
TI  - Two-step transcriptional amplification-lipid-based nanoparticles using PSMA or
      midkine promoter for suicide gene therapy in prostate cancer.
AB  - A two-step transcriptional amplification system (TSTA) was used to enhance the
      efficacy of suicide gene therapy for treatment of prostate cancer. We designed a
      TSTA system and constructed two types of plasmid: one containing GAL4-VP16 fusion
      protein under the control of a tumor-specific promoter, the other containing
      luciferase or herpes simplex virus thymidine kinase (HSV-tk) under the control of
      a synthetic promoter. The TSTA systems using nanoparticles based on lipids were
      evaluated by measuring the amount of induced luciferase activity as a function of
      prostate-specific membrane antigen (PSMA) and midkine (Mk) promoters, specific
      for LNCaP and PC-3 prostate cancer cells, respectively. In LNCaP cells that were
      PSMA-positive, the TSTA system featuring the PSMA enhancer and promoter exhibited
      activity that was 640-fold greater than a system consisting of one-step
      transcription with the PSMA promoter. In contrast, this difference in activity
      did not occur in PSMA-negative PC-3 cells. In Mk-positive PC-3 cells, the TSTA
      system with the Mk promoter exhibited a five-fold increase in activity over one
      step transcription, but such activity was not induced in Mk-negative LNCaP cells.
      When using HSV-tk for suicide gene therapy, TSTA systems featuring the PSMA or Mk
      promoter inhibited in vitro cell growth in the presence of ganciclovir.
      Furthermore, the TSTA system featuring the Mk promoter suppressed in vivo growth
      of PC-3 tumor xenografts to a greater extent than one-step transcription. These
      findings show that TSTA systems can enhance PSMA and Mk promoter activities and
      selectively inhibit PC-3 cell growth in tumors. This suggests that TSTA systems
      featuring tumor-specific promoters are suitable for cancer treatment by gene
      therapy.

PMID- 16800822
TI  - Effects of genetic polymorphisms of MDR1, FMO3 and CYP1A2 on susceptibility to
      colorectal cancer in Koreans.
AB  - The aim of the present study was to evaluate the effects on the susceptibility to
      colorectal cancer (CRC) of genetic polymorphisms in P-glycoprotein (PGP) and the
      metabolic enzymes cytochrome P450 1A2 (CYP1A2) and flavin-containing
      monooxygenase 3 (FMO3). We analyzed five single-nucleotide polymorphisms (SNP) in
      93 cancer-free volunteers and 111 patients with CRC: one common genetic variant
      of the PGP-encoding MDR1 gene and four SNP in genes for metabolic enzymes (two
      SNP in FMO3 and two SNP in CYP1A2). The genotypes and allele frequencies of the
      MDR1/C3435T, FMO3/G488A, FMO3/A923G and CYP1A2/G-3860 A polymorphisms were not
      significantly different in cancer-free subjects and CRC patients. However, a
      significant association was found between the CYP1A2/A-163C polymorphism and the
      risk of CRC, particularly in elderly (>55 years) subjects and smokers. A
      phenotyping study in normal smokers showed that the CYP1A2 activity of subjects
      with the CYP1A2/-163 AA genotype was significantly lower than that of subjects
      carrying the CYP1A2/-163C allele. Combined results show that the CYP1A2/-163C
      allele is significantly associated with an increase in CYP1A2 activity and a
      consequent increased risk of CRC in Koreans, particularly in elderly people and
      smokers.

PMID- 16800823
TI  - Association of the OGG1-Ser326Cys polymorphism with lung adenocarcinoma risk.
AB  - Adenocarcinoma (ADC) is the most frequent histological type of lung cancer and
      comprises the majority of lung cancers in non-smokers. Thus, genetic factors
      responsible for ADC susceptibility need to be determined to establish efficient
      ways of preventing the disease. The OGG1 gene, encoding a glycosylase for 8
      hydroxyguanine, an oxidatively damaged promutagenic base, has the polymorphism
      Ser326Cys, and OGG1-326Cys protein was indicated to have a lower ability to
      prevent mutagenesis than the OGG1-326Ser protein. Case-control studies to date
      suggest that the OGG1-326Cys allele is associated with a higher risk for several
      types of cancers, including overall lung cancer. However, the contribution of
      this polymorphism to lung ADC risk is unclear. In the present study, the OGG1
      Ser326Cys polymorphism was assessed for association with lung ADC risk using a
      case-control study of a Japanese population consisting of 1097 cases and 394
      controls. Odds ratios (OR) of the 326Cys allele carriers increased in a dose
      dependent manner with allele number (P for the trend test = 0.04). The OR of
      homozygotes for the 326Cys allele was increased significantly when homozygotes
      for the 326Ser allele were used as a reference (OR = 1.5, 95% confidence interval
      [CI] = 1.0-2.1, P = 0.04). Furthermore, the overall OR for lung ADC of the
      Cys/Cys homozygotes out of a total of 1925 ADC patients and 3449 controls from
      six case-control studies reported up to the present were 1.43 (95% CI = 1.11
      1.84, P = 0.0045). These results indicate that OGG1-326Cys functions as a risk
      allele for lung ADC development.

PMID- 16800825
TI  - Different effects of chronic phencyclidine on brain-derived neurotrophic factor
      in neonatal and adult rat brains.
AB  - The N-methyl-D-aspartate (NMDA) receptor and brain-derived neurotrophic factor
      (BDNF) are both known to play major roles in the normal development of the brain.
      We have hypothesized that the chronic blockade of NMDA with phencyclidine (PCP)
      may have a different effect on BDNF synthesis at different stages of development.
      In an acute experiment, rat pups and adult rats were injected with PCP (2.5, 5 or
      10 mg/kg) at postnatal day (PD) 15 or 49, respectively. In a chronic experiment,
      rat pups were injected daily from PD 5 to PD 14 with PCP (2.5, 5 or 10 mg/kg),
      while adult rats were injected daily with the same dose from PD 39 to PD 48. BDNF
      levels in the hippocampus, striatum and frontal cortex were determined by ELISA
      assay 24 hours after the last injection. Chronic PCP treatment of neonatal rats
      induced a dose-dependent decrease in BDNF in the hippocampus but not in the
      frontal cortex and striatum. Single injection of PCP to rat pups showed a slight
      reduction of BDNF in the hippocampus but only at higher doses. In contrast to
      neonatal brain, neither acute nor chronic injection of PCP influenced BDNF in
      adult brain. These findings suggest that chronic blockade of NMDA receptor in the
      early neonatal period has an inhibitory effect on BDNF synthesis in the
      hippocampus and may impair normal neurodevelopment in rat pups.

PMID- 16800824
TI  - Movement disorders and alcohol misuse.
AB  - Many movement disorders, including tics, chorea, tremor, myoclonus and
      parkinsonism, may result from substance abuse. However, alcohol in particular is
      associated in a more complex manner with two specific movement disorders,
      essential tremor (ET) and myoclonus-dystonia (M-D). In this review we discuss the
      comorbidity of alcohol abuse in both ET and M-D, the ameliorative effects of
      alcohol in both diseases, and review the data evaluating alcohol abuse secondary
      to self-medication. We also discuss shared pathophysiologic mechanisms in the
      understanding of both of these disorders, as the elucidation of the mechanisms by
      which alcohol exerts its effects may lead to novel therapeutic approaches.

PMID- 16800826
TI  - Long-term voluntary consumption of MDMA and THC in rats is modified by individual
      and situational factors.
AB  - Factors influencing long-term voluntary intake of 3,4
      methylenedioxymethamphetamine (MDMA; ecstasy) and Delta9-tetrahydrocannabinol
      (THC; cannabis) were studied in a rat model. Sixty-four male Wistar rats were
      given free choice for 49 weeks between (1) water and MDMA solution, (2) water and
      THC solution or (3) water, MDMA solution and THC solution. After the first
      experiences with the drugs, animals of both monodrug and polydrug group developed
      an individually stable pattern of MDMA consumption, whereas the individual
      predictability of THC consumption remained poor. While THC consumption was
      maintained for the whole experimental period, MDMA consumption decreased with
      time and was nearly ceased after 3-7 months. Intake of both drugs was adapted to
      social changes, with THC consumption being more sensitive to social changes than
      MDMA consumption. In the re-test after 4 months of abstinence, all animals ceased
      drug consumption when the drug solutions were adulterated with bitter tasting
      quinine. The results show that the rats had maintained a flexible mode of drug
      consumption and had not become addicted. Response to novelty of the rats in test
      trials before the start of drug supply correlated with later MDMA intake. In
      conclusion, although very low amounts of MDMA and/or THC were consumed, the
      findings that drug-experienced animals responded differentially to a stressor and
      that housing conditions influenced drug intake suggests that MDMA and THC can
      induce psychopharmacological effects in our long-term voluntary consumption
      paradigm.

PMID- 16800827
TI  - Effects of aqueous, methanolic and chloroform extracts of rhizome and aerial
      parts of Valeriana officinalis L. on naloxone-induced jumping in morphine
      dependent mice.
AB  - In the present study, the effects of rhizomes and aerial parts extracts of
      Valeriana officinalis L. on morphine dependence in mice have been investigated.
      Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three
      times daily (10 am, 1 pm and 4 pm) for 3 days, and a last dose of morphine (50
      mg/kg) was administered on the fourth day. Withdrawal syndrome (jumping) was
      precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2
      hours after the last dose of morphine. To study the effects of the aqueous,
      methanolic and chloroform extracts of both aerial parts and rhizome of the V.
      officinalis L. on naloxone-induced jumping in morphine-dependent animals, 10
      injections of morphine (three administrations each day) for dependence and a dose
      of 5 mg/kg of naloxone for withdrawal induction were employed. Intraperitoneal
      injection of different doses (1, 5, 25 and 50 mg/kg) of aqueous, methanolic and
      chloroform extracts of the rhizome of V. officinalis L. 60 minutes before
      naloxone injection decreased the jumping response dose-dependently. Pre-treatment
      of animals with different doses (1, 5, 25, 50 and 100 mg/kg) of aqueous and
      methanolic extracts of aerial parts of V. officinalis L. 60 minutes before
      naloxone injection caused a significant decrease on naloxone-induced jumping. The
      chloroform extract of the aerial parts of V. officinalis L. did not show any
      significant changes on jumping response in morphine-dependent animals. It is
      concluded that the extracts of V. officinalis L. could affect morphine withdrawal
      syndrome via possible interactions with inhibitory neurotransmitters in nervous
      system.

PMID- 16800828
TI  - The polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene is not
      associated with the diagnosis of alcoholism or alcohol withdrawal seizures.
AB  - As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates
      ethanol consumption, alcohol withdrawal symptoms and seizure generation by
      interacting with the GABAB receptor, the genes encoding for the GABAB receptor
      can be considered as candidate genes for alcoholism and alcohol withdrawal
      seizures (AWS). As the polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor
      gene had been associated with alcoholism and EEG abnormalities in prior studies,
      the present examination investigated if the polymorphism is associated with the
      diagnosis of alcoholism or AWS. After genotyping the allele and genotype
      frequencies of a group of alcoholics with a history of AWS (n = 69) were compared
      with the results of a group of alcoholics with only mild withdrawal symptoms (n =
      97). Additionally a group of healthy controls (n = 101) was compared with
      individuals with the diagnosis of alcoholism (n = 220). As no significant
      differences were found between the compared groups, this study gave no further
      evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.

PMID- 16800829
TI  - Cortisol concentrations, stress-coping styles after withdrawal and long-term
      abstinence in alcohol dependence.
AB  - Alcohol-dependent patients face a substantial risk of relapse after
      detoxification. A major risk factor for relapse is stress which is reflected
      biologically by various physiological changes that include an activation of the
      hypothalamic-pituitary-adrenal (HPA) axis and release of glucocorticoids. The
      prospective study examined cortisol concentrations and stress-coping styles in
      relation to abstinence 1 year following discharge from treatment. Cortisol
      concentrations were measured in the plasma of 46 alcohol-dependent patients (12
      women) on initial presentation for treatment (day 1), and again in plasma and in
      cerebrospinal fluid (CSF) after 6 weeks of abstinence (day 40). These results
      were compared with those of 26 age- and sex-matched, healthy control subjects.
      After withdrawal, the patients completed a comprehensive baseline assessment
      including a stress-coping questionnaire (Stressverarbeitungsfragebogen SVF120)
      and were monitored for 1 year after discharge. Negative stress-coping styles
      (e.g. flight, resignation) positively correlated with higher cortisol
      concentration in plasma and in CSF after withdrawal (day 40). Compared with
      relapsers after 1 year, abstainers had significantly lower levels for cortisol in
      CSF, whereas the stress-coping styles did not differ between abstainers and
      relapsers in this sample. These findings suggest that relatively stable
      personality traits like stress-coping styles have no measurable influence on
      abstinence. The lower cortisol concentration in CSF as an indicator for HPA axis
      functioning is associated with long-term abstinence in detoxified alcoholics.

PMID- 16800830
TI  - Quantification of breath carbon disulphide and acetone following a single dose of
      disulfiram (Antabuse) using selected ion flow tube mass spectrometry (SIFT-MS).
AB  - Selected ion flow tube mass spectrometry (SIFT-MS) has been used to measure
      simultaneously the concentrations of both carbon disulphide and acetone in
      exhaled breath following the ingestion of a single dose of disulfiram (Antabuse).
      Carbon disulphide is a product of the metabolism of disulfiram and is excreted
      mainly through the lungs. Acetone is a product of normal metabolism and appears
      in the breath of all individuals. These breath analyses were performed in single
      exhalations and the results were available in real time. The levels of breath
      acetone and carbon disulphide were compared with levels obtained from a control
      subject who had not ingested disulfiram. Breath carbon disulphide was seen to
      increase from 15 p.p.b. to 618 p.p.b. over a 28-hour period, in the single
      individual tested, following ingestion of disulfiram, while acetone levels
      increased from 300 p.p.b. (normal) to over 4000 p.p.b. (greatly elevated). No
      such increases were seen in the breath of the control subject over the same
      period. An obvious positive correlation between breath carbon disulphide and
      acetone concentrations following disulfiram ingestion is seen and discussed.

PMID- 16800831
TI  - Fluctuations in (R,S)-methadone pharmacokinetics and response among long-term
      methadone maintenance patients.
AB  - Knowledge of how methadone disposition may fluctuate during the course of
      maintenance treatment is presently limited. This study investigated long-term
      fluctuations in methadone pharmacokinetics in five methadone maintenance patients
      who participated in two 24-hour testing sessions separated by at least one year.
      Results indicated substantial fluctuations between sessions in dose-corrected
      average steady-state plasma (R)-methadone concentrations (Cav), ranging from a
      51% decrease to a 466% increase. These fluctuations were not consistently
      associated with changes in methadone dose or self-reported withdrawal status. The
      plasma (S)-:(R)-methadone Cav ratio increased significantly (12%, P = 0.04)
      between the sessions, suggesting a different pattern of long-term change in the
      pharmacokinetics of each enantiomer over time. The pronounced and variable
      fluctuations in methadone disposition evident in these patients highlight the
      need for an individualized approach to patient dosing and monitoring.

PMID- 16800832
TI  - Endocrine alterations during a detoxification treatment with carbamazepine in
      male alcoholics.
AB  - This study aimed to evaluate the prevalence and time-course of endocrine
      alterations in male alcohol addicts during a detoxification treatment and to
      examine a possible relation between endocrine alterations and depressive symptoms
      and overall mental distress. Blood samples were drawn in 54 male alcohol addicts
      on admission, at day 7 of treatment and at day 14 on discharge. Endocrine
      analysis was performed for cortisol, luteinizing hormone, prolactin, androgens,
      free testosterone and 17beta-estradiol. Psychometric measures (Beck's depression
      inventory and the symptom checklist-90-R) were taken on admission and on
      discharge and were correlated with endocrine measures. Cortisol plasma levels
      were substantially increased at the beginning of the detoxification, whereas all
      other endocrine parameters were within the normal range. Although subjects
      depicted mild to moderate levels of depressive symptoms and mental distress,
      there were no correlations with endocrine variables. Further analysis revealed a
      high variation in sex steroid levels with approximately 55% of participants
      showing initial (n = 19) or developing (n = 11) hypogonadal values during
      detoxification. In conclusion, chronic alcohol consumption induces disturbances
      of gonadal function which are reversible in the majority of cases. However, few
      patients develop a hypogonadal state during detoxification. Initially increased
      cortisol levels indicate a bodily stress response with the onset of alcohol
      withdrawal but are not related to mental disturbances.

PMID- 16800833
TI  - Suppression of cue-induced heroin craving and cue-reactivity by single-trial
      transcutaneous electrical nerve stimulation at 2 Hz.
AB  - The purpose of the present study was to investigate the efficacy of 2 Hz
      transcutaneous electrical nerve stimulation (TENS) to reduce cue-induced heroin
      craving and the corresponding cardiovascular responses. Seventy heroin addicts
      with at least 1 month of abstinence were enrolled and randomly divided into two
      groups of 35, to receive single-trial 2 Hz TENS (TENS group) or mock TENS (mock
      group) during experimental procedure, respectively. They were required to express
      their degree of craving by visual analog scale before and after the presentation
      of a video-cue, and after TENS treatment, which lasted for 30 minutes. Heart rate
      and arterial blood pressure were simultaneously monitored in 56 cases, with 28 in
      each group. Results show that in mock group, video-cue induced a dramatic
      increase of craving score, which did not return to baseline in 150 minutes,
      whereas in the TENS group, 2 Hz TENS treatment produced a significant decrease of
      craving, reaching baseline in 90 minutes. Video-cue induced a significant
      increase of heart rate and systolic and diastolic blood pressure, which remained
      elevated for at least 60 minutes in the mock group; whereas in the TENS group,
      they returned to baseline immediately after the termination of TENS. These
      results indicate that the craving induced by a heroin-related cue can be
      immediately and significantly suppressed, and the cardiovascular activation
      totally abolished by a single-trial 2 Hz TENS for 30 minutes.

PMID- 16800837
TI  - Treatment persistence with once-monthly ibandronate and patient support vs. once
      weekly alendronate: results from the PERSIST study.
AB  - Osteoporosis is a common and debilitating condition associated with significant
      morbidity and mortality. The efficacy and safety of oral bisphosphonates for the
      treatment of osteoporosis are well established. However, patient adherence and
      persistence on treatment are suboptimal. This randomised open-label multi-centre
      study of 6-months' duration compared persistence on treatment in postmenopausal
      women with osteoporosis receiving either once-monthly ibandronate plus a patient
      support programme (PSP), or once-weekly alendronate. To avoid falsely elevated
      persistence rates often associated with clinical trials, the study was designed
      to reflect everyday clinical practice in the UK and follow-up visits were limited
      to be consistent with the primary care setting. Analysis of the primary endpoint
      showed that persistence was significantly higher in the ibandronate/PSP group
      compared with the alendronate group (p < 0.0001). The estimated proportion of
      patients persisting with treatment at 6 months was 56.6% (306/541) and 38.6%
      (198/513) in the ibandronate/PSP and alendronate groups, respectively. Therefore,
      compared with alendronate, there was a 47% relative improvement in the proportion
      of patients persisting with treatment in the ibandronate/PSP group. Secondary
      endpoint measurements of adherence (e.g. proportion of patients remaining on
      treatment at study end; proportion of patients discontinuing from the study) were
      also significantly different in favour of ibandronate plus patient support. In
      summary, the PERSIST study demonstrated that persistence on treatment was
      increased in patients receiving once-monthly ibandronate plus patient support
      compared with once-weekly alendronate. Increased persistence on bisphosphonate
      treatment is expected to improve patient outcomes and decrease the social and
      economic burden of osteoporosis.

PMID- 16800839
TI  - Identification of HIV-1 Tat peptides for future therapeutic angiogenesis.
AB  - Therapeutic angiogenesis represents a novel approach to treat critical limb
      ischemia when revascularization is no more an option. The clinical use of the
      vascular endothelial growth factor is questioned, because of its side effects.
      This study was designed to identify and characterize human immunodeficiency virus
      type 1 (HIV-1) Tat-derived peptides based on their pro-angiogenic properties. A
      series of Tat-derived peptides were synthesized containing mutations in the basic
      domain. To minimize side effects Tat peptides were selected exerting no effects
      on the proteasome and on the viability of human umbilical vein endothelial cells
      (HUVEC). Tatpep5, 15, and 16 increased the endogenous levels of the pro
      angiogenic transcription factors c-Jun and SP-1 as well as the production of the
      plasminogen activator inhibitor-1 (PAI-1) by HUVEC. A significant induction of
      endothelial cell invasion was observed upon treatment of HUVEC with Tat peptides.
      In addition, selected Tat peptides induced tube formation by HUVEC as visualized
      and quantified in a Matrigel matrix. Our data demonstrate that the selected Tat
      peptides fulfill essential criteria for pro-angiogenic substances. They represent
      the basis for the development of novel pro-angiogenic drugs for future
      therapeutic angiogenesis, which might be applied for treatment of
      unreconstructible critical limb ischemia.

PMID- 16800841
TI  - Serum levels of sCD137 (4-1BB) ligand are prognostic factors for progression in
      acute myeloid leukemia but not in non-Hodgkin's lymphoma.
AB  - CD178 (Fas/APO-1 ligand) and CD137 ligand (CD137L) have previously been described
      in sera of patients with various malignancies and play an important role in the
      pathogenesis of various diseases. Recently, we demonstrated that low levels of
      soluble (s) CD137L and high levels of sCD178 correlate significantly with a long
      progression free survival in patients with myelodysplastic syndrome (MDS). In
      this study, we correlated sCD137L and sCD178 levels in sera of 42 samples of
      patients with acute myeloid leukemia (AML) and 46 samples of patients with non
      Hodgkin's lymphoma (NHL) with stages, subtypes, and the clinical course of the
      diseases and determined cut-off values with maximum probability for significant
      differentiation between cases with higher/lower probability for progress free
      survival. In contrast to patients with MDS, surprisingly no correlation between
      sCD178 levels and different subtypes and stages or with prognosis in AML or NHL
      were observed. Regarding sCD137L, NHL-patients displayed lower levels compared
      with AML. Statistically significant higher median levels of sCD137L are present
      in patients with undifferentiated AML (M1/M2, 1,470 pg/mL), poor cytogenetic risk
      (288 pg/mL) and higher levels of BM-blasts (186 pg/mL) compared with patients
      with monocytoid AML (M4/M5, 89 pg/mL), intermediate cytogenetic risk (59 pg/mL)
      and lower levels of BM-blasts (14 pg/mL) respectively. Furthermore, in AML
      patients sCD137L levels correlate significantly with the probabilities to achieve
      complete remission (CR), stay in CR or with progress of the disease. Taken
      together, our data demonstrate that sCD137L can be used as a prognostic factor
      not only in MDS but also in AML.

PMID- 16800840
TI  - The impact of genotype on endocrine complications in thalassaemia major.
AB  - BACKGROUND: The clinical severity in thalassaemia major (TM) depends on the
      underlying mutations of the beta-globin gene and the degree of iron overload.
      OBJECTIVE: The aim of the study was to investigate the impact of genotype on the
      development of endocrine complications in TM in our center. SUBJECTS AND METHODS:
      126 (62 males, 64 females) thalassaemic patients of Greek Cypriot origin with a
      mean age of 31.2 (17-68) yr were included in the study. All patients, who were on
      the standard treatment protocol, were subsequently divided into two groups
      according to their genotype, group A (92): TM with no mitigating factor and group
      B (34): TM carrying one or more mitigating factors in the beta- and/or alpha
      globin genes. Iron overload calculation was based on the amount of red cell
      consumption and the mean ferritin level over a 12-year period. Statistical
      analysis was performed with the SPSS program. RESULTS: Patients in group A, who
      were consuming larger amounts of blood on transfusions, were more likely to
      develop hypogonadism (P = 0.001) compared with patients in group B, despite their
      similar mean ferritin levels. The incidence of other endocrinopathies (short
      stature, hypothyroidism, and diabetes mellitus) was similar in the two groups.
      The prevalence of hypothyroidism in splenectomized patients was significantly
      higher (P = 0.005), whereas the presence of hypogonadism, impaired glucose
      homeostasis and insulin resistance, although more frequent, was not statistically
      significant. The clinical severity of TM had no impact on bone mineral density
      (BMD) in both men and women. BMD was only influenced by gonadal function.
      CONCLUSIONS: This study demonstrates that the underlying genetic defect in TM is
      a contributing factor for gonadal dysfunction, because the patients with the more
      severe defects have a greater rate of iron loading through higher red cell
      consumption.

PMID- 16800842
TI  - Effect of drug-induced cytotoxicity on glucose uptake in Hodgkin's lymphoma
      cells.
AB  - BACKGROUND: In Hodgkin's lymphoma, F-18-fluoro-deoxy-d-glucose positron emission
      tomography (FDG-PET) is used for staging and response evaluation after
      chemotherapy. However, drug-mediated downregulation of glucose uptake in viable
      Hodgkin's lymphoma cells might limit the use of FDG-PET. METHODS: We analyzed the
      effect of etoposide on cell viability and uptake of F-18-fluoro-deoxy-D-glucose
      or the glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2
      deoxyglucose (2-NBDG) in vitro. RESULTS: Etoposide induced a dose-dependent
      cytotoxicity in HDLM-2 cells which was significantly correlated with reduced FDG
      uptake. However, it also significantly increased the portion of viable cells
      which did not take up 2-NBDG. Interestingly, etoposide-induced cytotoxicity was
      mainly mediated via caspase-dependent mechanisms, whereas the cell death induced
      by deprivation of glucose was mediated via caspase-independent mechanisms.
      CONCLUSION: Etoposide-mediated reduction of glucose uptake by Hodgkin's lymphoma
      cells is mainly caused by cell death. In a small fraction of viable cells,
      etoposide might downregulate glucose transporters and/or hexokinase activity and
      by that inhibit glucose uptake. This, however, might not lead to false-negative
      results of response evaluation in Hodgkin's lymphoma patients after chemotherapy,
      because inhibition of glucose uptake itself seems to be a strong inducer of cell
      death. Altogether, this study provides important in vitro evidence to clarify the
      mechanisms by which FDG-PET monitors the effect of anti-cancer treatment in
      Hodgkin's lymphoma patients.

PMID- 16800843
TI  - Prophylactic ankle bracing reduces rearfoot motion during sudden inversion.
AB  - The purpose of this study was to evaluate the effects of ankle bracing on
      rearfoot angular displacement and angular velocity during a sudden inversion
      movement. A 1 x 3 factorial design was used. The single independent variable was
      ankle brace condition with three levels: semi-rigid, lace-up and control. The two
      dependent variables were rearfoot average angular displacement and average
      angular velocity. Twenty-four healthy volunteers participated in this study. A
      motion analysis system was used to capture, model and calculate two-dimensional
      rearfoot motion while the subjects' ankle/foot complex was inverted to 35 degrees
      on a platform device. All subjects performed five trials of each ankle brace
      condition, and the average of these trials was used for statistical analysis. The
      semi-rigid brace significantly reduced rearfoot angular displacement and angular
      velocity compared with the lace-up (P<0.05) and control conditions (P<0.05).
      Additionally, the lace-up style brace demonstrated significantly less rearfoot
      angular displacement and angular velocity compared with the control condition
      (P<0.05). These results demonstrate that a semi-rigid ankle brace is more
      superior then a lace-up style brace in limiting rearfoot angular displacement and
      angular velocity. Moreover, the lace-up style brace offers significant
      restriction of these measures compared with no support.

PMID- 16800845
TI  - Dynamics of the male germline stem cell population during aging of Drosophila
      melanogaster.
AB  - Drosophila melanogaster has emerged as an important model system for the study of
      both stem cell biology and aging. Much is known about how molecular signals from
      the somatic niche regulate adult stem cells in the germline, and a variety of
      environmental factors as well as single point mutations have been shown to affect
      lifespan. Relatively little is known, however, about how aging affects specific
      populations of cells, particularly adult stem cells that may be susceptible to
      aging-related damage. Here we show that male germline stem cells (GSCs) are lost
      from the stem cell niche during aging, but are efficiently replaced to maintain
      overall stem cell number. We also find that the division rate of GSCs slows
      significantly during aging, and that this slowing correlates with a reduction in
      the number of somatic hub cells that contribute to the stem cell niche.
      Interestingly, slowing of stem cell division rate was not observed in long-lived
      methuselah mutant flies. We finally investigated whether two mechanisms that are
      thought to be used in other adult stem cell types to minimize the effects of
      aging were operative in this system. First, in many adult tissues stem cells
      exhibit markedly fewer cell cycles relative to transit-amplifying cells,
      presumably protecting the stem cell pool from replication-associated damage.
      Second, at any given time not all stem cells actively cycle, leading to 'clonal
      succession' from the reserve pool of initially quiescent stem cells. We find that
      neither of these mechanisms is used in Drosophila male GSCs.

PMID- 16800846
TI  - Methionine restriction decreases visceral fat mass and preserves insulin action
      in aging male Fischer 344 rats independent of energy restriction.
AB  - Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction
      (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are
      unclear, both regimens feature lower body weight and reductions in adiposity.
      Reduced fat deposition in CR is linked to preservation of insulin responsiveness
      in older animals. These studies examine the relationship between insulin
      responsiveness and visceral fat in MR and test whether, despite lower food intake
      observed in MR animals, decreased visceral fat accretion and preservation of
      insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf)
      control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks
      exhibit insulin, glucose, and leptin levels similar to control-fed animals and
      comparable amounts of visceral fat. Conversely, MR rats show significantly
      reduced visceral fat compared to CF and PF with concomitant decreases in basal
      insulin, glucose, and leptin, and increased adiponectin and triiodothyronine.
      Daily energy expenditure in MR animals significantly exceeds that of both PF and
      CF. In a separate cohort, insulin responses of older MR animals as measured by
      oral glucose challenge are similar to young animals. Longitudinal assessments of
      MR and CF through 112 weeks of age reveal that MR prevents age-associated
      increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in
      insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1
      levels decline much later, beginning at 112 weeks. Collectively, the results
      indicate that MR reduces visceral fat and preserves insulin activity in aging
      rats independent of energy restriction.

PMID- 16800847
TI  - Functional dissection of SseF, a type III effector protein involved in
      positioning the salmonella-containing vacuole.
AB  - Intracellular replication of Salmonella enterica requires the formation of a
      unique organelle termed Salmonella-containing vacuole (SCV). The type III
      secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2-T3SS)
      has a crucial role in the formation and maintenance of the SCV. The SPI2-T3SS
      translocates a large number of effector proteins that interfere with host cell
      functions such as microtubule-dependent transport. We investigated the function
      of the effector SseF and observed that this protein is required to maintain the
      SCV in a juxtanuclear position in infected epithelial cells. The formation of
      juxtanuclear clusters of replicating Salmonella required the recruitment of
      dynein to the SCV but SseF-deficient strains were highly reduced in dynein
      recruitment to the SCV. We performed a functional dissection of SseF and defined
      domains that were important for translocation and the specific effector functions
      of this protein. Of particular importance was a hydrophobic domain in the C
      terminal half that contains three putative transmembrane (TM) helices. Deletion
      of one of these TM helices ablated the effector functions of SseF. We observed
      that this domain was essential for the proper intracellular positioning of the
      SCV to a juxtanuclear, Golgi-associated localization. These data show that SseF,
      in concert with the effector proteins SifA and SseG mediate the precise
      positioning of the SCV by differentially modulating the recruitment of
      microtubule motor proteins to the SCV.

PMID- 16800848
TI  - Activation of D1 dopamine receptors increases surface expression of AMPA
      receptors and facilitates their synaptic incorporation in cultured hippocampal
      neurons.
AB  - Considerable evidence indicates that neuroadaptations leading to addiction
      involve the same cellular processes that enable learning and memory, such as long
      term potentiation (LTP), and that psychostimulants influence LTP through dopamine
      (DA)-dependent mechanisms. In hippocampal CA1 pyramidal neurons, LTP involves
      insertion of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)
      receptors into excitatory synapses. We used dissociated cultures to test the
      hypothesis that D1 family DA receptors influence synaptic plasticity in
      hippocampal neurons by modulating AMPA receptor trafficking. Brief exposure (5
      min) to a D1 agonist increased surface expression of glutamate receptor (GluR)1
      containing AMPA receptors by increasing their rate of externalization at
      extrasynaptic sites. This required the secretory pathway but not protein
      synthesis, and was mediated mainly by protein kinase A (PKA) with a smaller
      contribution from Ca2+-calmodulin-dependent protein kinase II (CaMKII). Prior D1
      receptor stimulation facilitated synaptic insertion of GluR1 in response to
      subsequent stimulation of synaptic NMDA receptors with glycine. Our results
      support a model for synaptic GluR1 incorporation in which PKA is required for
      initial insertion into the extrasynaptic membrane whereas CaMKII mediates
      translocation into the synapse. By increasing the size of the extrasynaptic GluR1
      pool, D1 receptors may promote LTP. Psychostimulants may usurp this mechanism,
      leading to inappropriate plasticity that contributes to addiction-related
      behaviors.

PMID- 16800849
TI  - Tissue-type plasminogen activator rescues neurones from serum deprivation-induced
      apoptosis through a mechanism independent of its proteolytic activity.
AB  - Although the mechanism of action of tissue-type plasminogen activator (tPA) in
      excitotoxic necrosis is well documented, whether this serine protease can
      influence the apoptotic cascade remains a subject of debate. Here, we report that
      tPA protects cultured cortical neurones against apoptotic cell death induced by
      serum deprivation, an effect associated with a reduction of caspase-3 activation.
      Interestingly, blocking tPA proteolytic activity by either tPA stop or
      neuroserpin did not prevent this neuroprotection. Similarly, prevention of the
      interaction between tPA and its receptor low-density lipoprotein receptor-related
      protein (LRP) could not alter tPA anti-apoptotic activity. Interestingly, the
      survival-promoting effect of tPA was blocked by the phosphatidylinositol-3 (PI-3)
      kinase inhibitor, LY294002, but not by the mitogen-activated protein (MAP) kinase
      inhibitor, U0126. In conclusion, the present demonstration of an anti-apoptotic
      effect of tPA, independent of its enzymatic activity, reveals an additional level
      of complexity in our understanding of this critical mediator of brain physiology
      and pathology.

PMID- 16800850
TI  - The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a
      major actor at the brain excitatory synapse?
AB  - EAAC1/EAAT3 is a transporter of glutamate (Glu) present at the post-synaptic
      neuronal element, in opposition to the two other main transporters, GLAST/EAAT1
      and GLT1/EAAT2, expressed at the excitatory amino acid (EAA) synapse by
      surrounding astrocytes. Although, in the adult, EAAC1/EAAT3 exhibits a rather low
      expression level and is considered to make a minor contribution to Glu removal
      from the synapse, its early expression during brain development, before the
      astrocytes are functional, suggests that such a neuronal transporter is involved
      in the developmental effects of EAA and, possibly, in the biosynthesis and
      trophic role of GABA, which is excitatory in nature in different brain regions
      during the earlier stages of brain development. This neuronal Glu transporter is
      considered to have a dual action as it is apparently involved in the neuronal
      uptake of cysteine, which acts as a key substrate for the synthesis of
      glutathione, a major anti-oxidant, because the neurones do not express the Xc(-)
      transport system in the mature brain. Interestingly, EAAC1/EAAT3
      activity/expression was shown to be highly regulated by neuronal activity as well
      as by intracellular signalling pathways involving primarily alpha protein kinase
      C (alphaPKC) and phosphatidylinositol-3-kinase (PI3K). Such regulatory processes
      could act either at the post-traductional level or at the transcriptional level.
      It is worth noting that EAAC1/EAAT3 exhibits specificity, compared with other EAA
      transporters, because it is present mainly in the intracellular compartment and
      only for about 20% at the plasma membrane. Variations in neuronal Glu uptake were
      shown to be associated with rapid changes in the trafficking of the transporter
      protein altering the membranar location of the transporter. More recent data show
      that astrocyte-secreted factors such as cholesterol could also influence rapid
      changes in the location of EAAC1/EAAT3 between the plasma membrane and the
      cytoplasmic compartment. Such a highly regulated process of EAAC1/EAAT3
      activity/expression may have implications in the physiopathology of major
      diseases affecting EAA brain signalling, which is further supported by data
      obtained in animal models of hypoxia-anoxia, for example.

PMID- 16800851
TI  - Multiple promoter elements required for leukemia inhibitory factor-stimulated M2
      muscarinic acetylcholine receptor promoter activity.
AB  - Treatment of neuronal cells with leukemia inhibitory factor (LIF) results in
      increased M(2) muscarinic acetylcholine receptor promoter activity. We
      demonstrate here that multiple promoter elements mediate LIF stimulation of M(2)
      gene transcription. We identify a LIF inducible element (LIE) in the M(2)
      promoter with high homology to a cytokine-inducible ACTG-containing sequence in
      the vasoactive intestinal peptide promoter. Mutagenesis of both a STAT (signal
      transducers and activators of transcription) element and the LIE in the M(2)
      promoter is required to attenuate stimulation of M(2) promoter activity by LIF
      completely. Mobility shift assays indicate that a LIF-stimulated complex binds to
      a 70 base pair M(2) promoter fragment. Furthermore, a STAT element within this
      fragment can bind to LIF-stimulated nuclear STAT1 homodimers in vitro.
      Mutagenesis experiments show that cytokine-stimulated activation of M(2) promoter
      activity requires tyrosine residues on glycoprotein 130 (gp130) that are also
      required for both STAT1 and STAT3 activation. Dominant negative STAT1 or STAT3
      can block LIF-stimulated M(2) promoter activity. Real-time RT-PCR analysis
      indicates that LIF-stimulated induction of M(2) mRNA is partially dependent on
      protein synthesis. These results show that regulation of M(2) gene transcription
      in neuronal cells by LIF occurs through a complex novel mechanism that is
      dependent on LIE, STAT and de novo protein synthesis.

PMID- 16800852
TI  - One slow pathway or two?

PMID- 16800853
TI  - Marshall vein as arrhythmogenic source in patients with atrial fibrillation:
      correlation between its anatomy and electrophysiological findings.
AB  - BACKGROUND: Atrial fibrillation (AF) may originate from catecholamine-sensitive
      vein of Marshall (VOM) or its ligament in addition to pulmonary veins (PVs). The
      anatomy of VOM and its relation to arrhythmogenic foci in the left atrium are
      unknown. We studied the anatomy of VOM and its relation to foci in patients with
      AF. METHODS: The study population consisted of 100 patients with AF (mean age, 62
      years; chronic AF, n = 15). AF sources were determined at baseline and after
      isoproterenol administration without sedation. VOM was identified by balloon
      occluded coronary sinus (CS) angiography. We determined its anatomy in relation
      to left PVs. RESULTS: VOM was visualized in 73 patients (73%). Ninety-seven
      patients had 269 arrhythmogenic foci (PV, n = 77; non-PV, n = 48). Non-PV foci
      included left atrial posterior wall (24, 9%), left lateral area (12, 4.5%), roof
      (6, 2.2%), superior vena cava (28, 10.4%), crista terminalis (8, 3.0%), CS (10,
      3.7%), and others (10, 3.7%). The incidence of PV foci in the left superior PV
      (LSPV) was significantly higher in patients with well-developed VOM than in those
      without (66% vs 42%, P < 0.05). Twenty-eight patients had 30 non-PV foci around
      the LSPV ostium. We successfully ablated the non-PV foci at the distal end of VOM
      in 11 patients. The ends of the VOM branches were good markers to search for non
      PV foci. Seven of 11 (64%) patients with successful ablation of non-PV foci were
      free from arrhythmia, whereas only 6 of 17 (35%) were free from arrhythmia in
      those with residual non-PV foci. CONCLUSIONS: To determine VOM anatomy is
      important to identify non-PV foci around the ends of VOM.

PMID- 16800854
TI  - Ankyrins and human disease: what the electrophysiologist should know.
AB  - The coordinate activity of ion channels and transporters in cardiac muscle is
      critical for normal excitation-contraction coupling and cardiac rhythm. In the
      past decade, human gene variants, which alter ion channel biophysical properties,
      have been linked with fatal cardiac arrhythmias. Ankyrins are a family of
      "adaptor" proteins, which play critical roles in the proper expression and
      membrane localization of ion channels and transporters in excitable and
      nonexcitable cells. Recent findings demonstrate a new paradigm for human cardiac
      arrhythmia based not on gene mutations that affect channel biophysical
      properties, but instead on mutations that affect ion channel/transporter
      localization at excitable membranes in heart. Human ANK2 mutations are associated
      with "ankyrin-B syndrome" (an atypical arrhythmia syndrome with risk of sudden
      cardiac death). Human gene mutations, which affect ankyrin-G-based pathways for
      voltage-gated Na(v) channel localization, are associated with Brugada syndrome, a
      second potentially fatal arrhythmia. Together, these data demonstrate the
      importance of the molecular events involved in the cellular organization of
      membrane domains in excitable cells. Moreover, these data define an exciting new
      field of cardiac "channelopathies" due to defects in proper channel
      targeting/localization.

PMID- 16800855
TI  - Right and left ventricular outflow tract tachycardias: evidence for a common
      electrophysiologic mechanism.
AB  - INTRODUCTION: "Idiopathic" ventricular arrhythmias most often arise from the
      right ventricular outflow tract (RVOT), although arrhythmias from the left
      ventricular outflow tract (LVOT) are also observed. While previous work has
      elucidated the mechanism and electropharmacologic profile of RVOT arrhythmias, it
      is unclear whether those from the LVOT share these properties. The purpose of
      this study was to characterize the electropharmacologic properties of RVOT and
      LVOT arrhythmias. METHODS AND RESULTS: One hundred twenty-two consecutive
      patients (61 male; 50.9 +/- 15.2 years) with outflow tract arrhythmias comprise
      this series, 100 (82%) with an RVOT origin, and 22 (18%) with an LVOT origin. The
      index arrhythmia was similar: sustained ventricular tachycardia (VT) (RVOT = 28%,
      LVOT = 36%), nonsustained VT (RVOT = 40%, LVOT = 23%), and premature ventricular
      complexes (RVOT = 32%, LVOT = 41%) (P = 0.32). Cardiac magnetic resonance imaging
      and microvolt T-wave alternans results (normal/indeterminate) were also
      comparable. In addition, 41% with RVOT foci and 50% with LVOT foci were inducible
      for sustained VT (P = 0.48), and induction of VT was catecholamine dependent in a
      majority of patients in both groups (66% and 73%; RVOT and LVOT, respectively; P
      = 1.0). VT was sensitive to adenosine (88% and 78% in the RVOT and LVOT groups,
      respectively, P = 0.59) as well as blockade of the slow-inward calcium current
      (RVOT = 70%, LVOT = 80%; P = 1.00) in both groups. CONCLUSIONS:
      Electrophysiologic and pharmacologic properties, including sensitivity to
      adenosine, are similar for RVOT and LVOT arrhythmias. Despite disparate sites of
      origin, these data suggest a common arrhythmogenic mechanism, consistent with
      cyclic AMP-mediated triggered activity. Based on these similarities, these
      arrhythmias should be considered as a single entity, and classified together as
      "outflow tract arrhythmias."

PMID- 16800856
TI  - Implantation of bilateral carotid artery filters to allow safe removal of left
      atrial thrombus during ablation of atrial fibrillation.
AB  - Left atrial clot formation is a feared complication of catheter ablation for
      atrial fibrillation. We report a case of left atrial thrombus that formed around
      the circular mapping catheter before the delivery of RF. Successful retrieval of
      the clot was obtained by withdrawing the catheters while protecting the anterior
      cerebral circulation by positioning temporary carotid artery filters.

PMID- 16800857
TI  - Ablation for atrioventricular nodal reentrant tachycardia with a prolonged PR
      interval during sinus rhythm: the risk of delayed higher-degree atrioventricular
      block.
AB  - INTRODUCTION: Delayed higher-degree atrioventricular (AV) block can develop after
      slow pathway ablation for AV nodal reentrant tachycardia with a preexisting first
      degree AV block. Retrograde fast pathway ablation is considered as an alternative
      approach for patients with a markedly prolonged PR interval and no demonstrable
      anterograde fast pathway function at baseline. This study aimed to determine the
      long-term reliability of AV conduction after retrograde fast pathway ablation in
      comparison to slow pathway ablation in patients with AV nodal reentrant
      tachycardia and a first-degree AV block at baseline. METHODS AND RESULTS: Among
      43 patients with AV nodal reentrant tachycardia and a prolonged PR interval
      (defined as >or=200 msec), 10 patients without demonstrable dual pathway
      physiology underwent ablation of the retrograde fast pathway, and 33 patients
      with dual pathway physiology underwent slow pathway ablation. Persisting
      intraprocedural second- or third-degree AV block requiring pacemaker implantation
      occurred in one patient (10%) after retrograde fast pathway ablation and in one
      patient (3%) after slow pathway ablation. During the long-term follow-up of 61 +/
      39 months after retrograde fast pathway ablation, no delayed second- or third
      degree AV block occurred, and the PR interval remained unchanged (308 +/- 60 msec
      vs 304 +/- 52 msec). During the follow-up of 37 +/- 25 months after slow pathway
      ablation, a delayed complete heart block developed in two patients, and a second
      degree AV block developed in two patients. Three patients aged 66, 75, and 76
      years died suddenly of unknown cause 4, 16, and 48 months following slow pathway
      ablation, respectively. CONCLUSIONS: Slow pathway ablation was associated with a
      significant risk of a delayed higher-degree AV block in patients with AV nodal
      reentrant tachycardia and a prolonged PR interval at baseline. Retrograde fast
      pathway ablation for patients with a first-degree AV block and no demonstrable
      dual pathway physiology was associated with a higher intraprocedural risk of
      complete AV block but did not result in the development of higher-degree AV block
      during the long-term follow-up of up to 9 years.

PMID- 16800858
TI  - Phrenic nerve injury after catheter ablation: should we worry about this
      complication?
AB  - INTRODUCTION: Phrenic nerve injury (PNI) is a complication that can occur with
      catheter ablation. METHODS: Data from 17 patients with PNI following different
      catheter ablation techniques were reviewed. PNI was defined as decreased motility
      (transient) or paralysis (persistent) of the hemi-diaphragm on fluoroscopy or
      chest X-ray. Patient's recovery was monitored. Normalization of chest images and
      sniff test would be considered as complete clinical recovery. RESULTS: Out of the
      17 PNI patients (16 right, 1 left), 13 (11 persistent, 2 transient) occurred
      after pulmonary veins isolation with or without superior vena cava ablation.
      Three patients had persistent PNI after sinus node modification and one other
      patient experienced PNI after epicardial ventricular tachycardia ablation.
      Ablation was performed with different energy source including radiofrequency (n =
      13), cryothermal (n = 1), ultrasound (n = 2) and laser (n = 1). Patient's
      symptoms varied broadly from asymptomatic to dyspnea, and even to respiratory
      insufficiency that required temporary mechanical ventilation support. Two
      patients with transient PNI resolved immediately after the procedure and the
      other 15 persistent PNI patients resolved within a mean time of 8.3 +/- 6.6
      months. CONCLUSIONS: PNI caused by catheter ablation appears to functionally
      recover over time regardless of the energy sources used for the procedure.

PMID- 16800859
TI  - Heritability of indices for cardiac contractility in ambulatory recordings.
AB  - INTRODUCTION: Overactivity of the sympathetic nervous system (SNS) plays a
      pivotal role in the development of cardiovascular disease. This involvement
      suggests that the genetic susceptibility to adverse cardiovascular events may
      derive in part from individual differences in SNS activity. METHODS AND RESULTS:
      To establish a genetic contribution to SNS activity, we measured sympathetic
      effects on cardiac contractility in 755 healthy adult twins and their singleton
      siblings. The preejection period (PEP) and the ratio of PEP to the left
      ventricular ejection time (PEP/LVET ratio) were derived from ambulatory
      recordings of the ECG and thorax impedance. During this type of prolonged
      recordings in a real life setting, the extent of cardiac sympathetic activity
      will vary with the demands of daily activities. Therefore, the genetic
      architecture of both indices was examined separately across three daytime periods
      (morning, afternoon, evening), and during nighttime sleep. Results showed
      significant genetic contribution to PEP (48-62%) over all daily periods.
      Heritability estimates for PEP/LVET ratio ranged between 35% and 58%. Cardiac
      sympathetic activity during the waking and sleep periods was largely influenced
      by genetic factors that were common to the entire 24-hour period. During sleep,
      additional genetic influences emerged that accounted for 8% of the variance in
      PEP. CONCLUSION: Impedance-derived measures of sympathetic effects on cardiac
      contractility show substantial heritability across all periods of the day and
      during sleep.

PMID- 16800861
TI  - Blood-CSF barrier function in the rat embryo.
AB  - Blood-cerebrospinal fluid (CSF) barrier function and expansion of the ventricular
      system were investigated in embryonic rats (E12-18). Permeability markers
      (sucrose and inulin) were injected intraperitoneally and concentrations measured
      in plasma and CSF at two sites (lateral and 4th ventricles) after 1 h. Total
      protein concentrations were also measured. CSF/plasma concentration ratios for
      endogenous protein were stable at approximately 20% at E14-18 and subsequently
      declined. In contrast, ratios for sucrose (100%) and inulin (40%) were highest at
      the earliest ages studied (E13-14) and then decreased substantially. Between E13
      and E16 the volume of the lateral ventricles increased over three-fold.
      Decreasing CSF/plasma concentration ratios for small, passively diffusing
      molecules during embryonic development may not reflect changes in permeability.
      Instead, increasing volume of distribution appears to be important in this
      decline. The intracellular presence of a small marker (3000 Da biotin
      dextranamine) in plexus epithelial cells following intraperitoneal injection
      indicates a transcellular route of transfer. Ultrastructural evidence confirmed
      that choroid plexus tight junctions are impermeable to small molecules at least
      as early as E15, indicating the blood-CSF barrier is morphologically and
      functionally mature early in embryonic development. Comparison of two albumins
      (human and bovine) showed that transfer of human albumin (surrogate for
      endogenous protein) was 4-5 times greater than bovine, indicating selective blood
      to-CSF transfer. The number of plexus epithelial cells immunopositive for
      endogenous plasma protein increased in parallel with increases in total protein
      content of the expanding ventricular system. Results suggest that different
      transcellular mechanisms for protein and small molecule transfer are operating
      across the embryonic blood-CSF interface.

PMID- 16800860
TI  - Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a
      murine model of asthma.
AB  - Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidases and in contact with mucosal surfaces generate superoxide anion (O2*-).
      In the presence of iron, O2*- may be converted to more reactive oxygen radicals,
      such as to H2O2 and/or *OH, which may augment antigen-induced airway
      inflammation. The aim of the study was to examine the impact of lactoferrin (LF),
      an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract
      (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial
      cells and accumulation of inflammatory and mucin-producing cells in airways in a
      mouse model of allergic airway inflammation. Results show that LF lowered RWE
      induced increase in cellular reactive oxygen species (ROS) levels in bronchial
      epithelial cells. Most importantly, LF significantly decreased accumulation of
      eosinophils into airways and subepithelium of intranasally challenged, sensitized
      mice. LF also prevented development of mucin-producing cells. Amb a 1, the major
      allergenic ragweed pollen antigen lacking NADPH oxidase activity, induced low
      grade airway inflammation. When administered along with glucose oxidase (G-ox), a
      superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which
      was significantly lowered by LF. Surprisingly, LF decreased also inflammation
      caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal
      effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced
      inflammation. We postulate that free iron in the airways chemically reduces O2*-
      to more reactive species which augment antigen-induced inflammation in a mouse
      model of asthma. Our results suggest the utility of LF in human allergic
      inflammatory disorders.

PMID- 16800862
TI  - Ultrastructural organization of medial prefrontal inputs to the rhinal cortices.
AB  - Accumulating evidence suggests that the medial prefrontal cortex (mPFC) plays a
      critical role in the formation, retrieval and long-term storage of hippocampal
      dependent memories. Consistent with this, there are direct hippocampal
      projections to the mPFC. Moreover, the mPFC sends robust projections to the
      perirhinal and entorhinal cortices, two interconnected cortical fields that
      funnel information into and out of the hippocampus. However, the significance of
      the latter projection remains unclear because no data are available regarding the
      rhinal targets of mPFC axons. This question was examined in the present study
      using a combination of anterograde tracing with Phaseolus vulgaris
      leucoagglutinin and pre-embedding gamma-aminobutyric acid (GABA)
      immunocytochemistry in guinea pigs. Following Phaseolus vulgaris leucoagglutinin
      injections in the mPFC, anterogradely labeled axons were seen in the perirhinal
      (mainly superficial layers) and lateral entorhinal (mainly deep layers) cortices.
      In the electron microscope, the synaptic articulation of anterogradely labeled
      mPFC axon terminals with perirhinal and entorhinal neurons was found to be nearly
      identical. In these two rhinal fields, mPFC axon terminals only formed asymmetric
      synapses, typically with GABA-immunonegative spines ( approximately 70%) but
      occasionally with dendritic profiles ( approximately 30%), half of which were
      GABA immunopositive. In the light of earlier observations, these findings
      indicate that mPFC inputs exert mainly excitatory effects in the rhinal cortices,
      prevalently on principal neurons. Thus, these results suggest that the mPFC may
      affect hippocampal-dependent memories by enhancing impulse traffic into and out
      of the hippocampus at the level of the rhinal cortices.

PMID- 16800863
TI  - TRPV1, but not P2X, requires cholesterol for its function and membrane expression
      in rat nociceptors.
AB  - We examined the importance of membrane cholesterol for the function and
      expression of TRPV1 (vanilloid receptor subtype 1) and P2X(3) in adult rat dorsal
      root ganglion (DRG) neurons. Cholesterol, an essential component of lipid rafts,
      was depleted using methyl beta-cyclodextrin (MCD). We found that MCD
      significantly reduced TRPV1-mediated capsaicin- and proton-activated currents. By
      contrast, inward currents activated by alpha,beta-methylene ATP (alpha,beta
      meATP), a non-hydrolysable ATP analogue, were not altered. Immunoreactivity for
      TRPV1, but not P2X(3), in the plasma membrane was markedly reduced by MCD. A
      reduction of TRPV1 protein in membrane fractions was found following cholesterol
      depletion. Our data show that the level of cholesterol determines the activity
      and the amount of membrane TRPV1, suggesting that TRPV1 might be localized in
      cholesterol-rich microdomains in nociceptors. The differential dependence on the
      membrane cholesterol of TRPV1 and P2X(3) may have physiological significance in
      nociception during inflammation.

PMID- 16800864
TI  - Ethanol withdrawal induces hyperalgesia mediated by PKCepsilon.
AB  - Symptoms of ethanol withdrawal include heightened responses to sensory stimuli,
      as well as tremors and convulsions. We tested the hypothesis that repeated
      episodes of ethanol intake and withdrawal exacerbate the symptoms of alcohol
      induced peripheral neuropathy. In contrast to the hyperalgesia produced when an
      alcohol (6.5%)-containing diet was fed continuously to male rats which took 4
      weeks to develop (Dina et al., 2000), feeding alcohol (6.5%) in repeated cycles
      of 4 days of alcohol followed by 3 days without alcohol resulted in a withdrawal
      induced hyperalgesia that began at the end of one weekly cycle and reached a
      maximum during the fourth cycle. For ethanol withdrawal to produce hyperalgesia,
      ethanol consumption needed to be terminated for a period of 2 days.
      Paradoxically, as the amount of alcohol consumed decreased, the hyperalgesia
      induced by withdrawal developed more rapidly, being maximal between 1.4 and 1.6%
      ethanol. These results suggest that continued exposure to ethanol also has a
      neuroprotective effect. Withdrawal-induced hyperalgesia, similar to the
      hyperalgesia induced by continuous, chronic alcohol intake, was inhibited
      reversibly by intrathecal administration of an antisense oligodeoxynucleotide to
      protein kinase C (PKC)epsilon.

PMID- 16800865
TI  - Negative cross-talk between presynaptic adenosine and acetylcholine receptors.
AB  - Functional interactions between presynaptic adenosine and acetylcholine (ACh)
      autoreceptors were studied at the frog neuromuscular junction by recording
      miniature end-plate potentials (MEPPs) during bath or local application of
      agonists. The frequency of MEPPs was reduced by adenosine acting on presynaptic
      adenosine A1 receptors (EC(50) = 1.1 microm) or by carbachol acting on muscarinic
      M2 receptors (EC(50) = 1.8 microm). However, carbachol did not produce the
      depressant effect when it was applied after the action of adenosine had reached
      its maximum. This phenomenon implied that the negative cross-talk (occlusion) had
      occurred between A1 and M2 receptors. Moreover, the occlusion was receptor
      specific as ATP applied in the presence of adenosine continued to depress MEPP
      frequency. Muscarinic antagonists [atropine or 1-[[2-[(diethylamino)methyl)-1
      piperidinyl]acetyl]-5,11-dihydro-6H-pyrido [2,3-b][1,4]benzodiazepine-6-one)
      (AFDX-116)] had no effect on the inhibitory action of adenosine and adenosine
      antagonists [8-(p-sulfophenyl)theophylline (8-SPT) or 1,3-dipropyl-8
      cyclopentylxanthine (DPCPX)] had no effect on the action of carbachol. These data
      suggested that membrane-delimited interactions did not occur between A1 and M2
      receptors. Both carbachol and adenosine similarly inhibited quantal release
      triggered by high potassium, ionomycin or sucrose. These results indicated a
      convergence of intracellular pathways activated by M2 and A1 receptors to a
      common presynaptic effector located downstream of Ca(2+) influx. We propose that
      the negative cross-talk between two major autoreceptors could take place during
      intense synaptic activity and thereby attenuate the presynaptic inhibitory
      effects of ACh and adenosine.

PMID- 16800866
TI  - Neuropeptide Y in the olfactory microvillar cells.
AB  - This paper examines a possible role of microvillar cells in coordinating cell
      death and regeneration of olfactory epithelial neurons. The olfactory
      neuroepithelium of mammals is a highly dynamic organ. Olfactory neurons
      periodically degenerate by apoptosis and as a consequence of chemical or physical
      damage. To compensate for this loss of cells, the olfactory epithelium maintains
      a lifelong ability to regenerate from a pool of resident multipotent stem cells.
      To assure functional continuity and histological integrity of the olfactory
      epithelium over a period of many decades, apoptosis and regeneration require to
      be precisely coordinated. Among the factors that have been implicated in
      mediating this regulation is the neuropeptide Y (NPY). Knockout mice that lack
      functional expression of this neurogenic peptide show defects in embryonic
      development of the olfactory epithelium and in its ability to regenerate in the
      adult. Here we show that, in postnatal olfactory epithelia, NPY is exclusively
      expressed by a specific population of microvillar cells. We previously
      characterized these cells as a novel type of putative chemosensory cells, which
      are provided with a phosphatidyl-inositol-mediated signal transduction cascade.
      Our findings allow for the first time to suggest that microvillar cells are
      involved in connecting apoptosis to neuronal regeneration by stimulus-induced
      release of NPY.

PMID- 16800867
TI  - Calcium-regulated potassium currents secure respiratory rhythm generation after
      loss of glycinergic inhibition.
AB  - Mutant oscillator mice (Glra1(spd -/-)) are characterized by a developmental loss
      of glycinergic inhibition. These mice die during the third postnatal week
      presumably due to gradually increasing disturbances of breathing and motor
      behaviour. Some irregular rhythmic respiratory activity, however, is persevered
      until they die. Here we analysed cellular mechanisms that compensate for the loss
      of glycinergic inhibition and contribute to the maintenance of the respiratory
      rhythm. In a medullary slice preparation including the pre-Botzinger complex we
      performed a comparative analysis of after-hyperpolarizations following action
      potentials (AP-AHP) and burst discharges (burst-AHP) in identified respiratory
      neurons from oscillator and control mice. Both AHP forms were increased in
      neurons from oscillator mice. These changes were combined with an augmented
      adaptation of firing frequency. Assuming that oscillator mice might upregulate
      calcium-activated K currents (BKCa) in compensation for the loss of glycinergic
      inhibition, we blocked the big KCa conductances with iberiotoxin and verified
      that the respiratory rhythm was indeed arrested by BK channel blockade.

PMID- 16800868
TI  - Internationally recruited nurses in London: a survey of career paths and plans.
AB  - BACKGROUND: The paper reports on a survey of recently arrived international
      nurses working in London, to assess their demographic profile, motivations,
      experiences and career plans. METHODS: A postal survey was conducted in October
      December 2004 on a sample of 1000 nurses who were London-based international
      members of the Royal College of Nursing (RCN). The usable response rate was 40%.
      Registration data from the Nurses and Midwives Council (NMC) were also analysed.
      RESULTS: The Philippines, Nigeria and South Africa were the three most commonly
      reported countries of training (in total, more than 30 countries of training were
      reported). Sixty per cent of the nurses from sub-Saharan Africa and more than 40%
      from South Africa and India/Pakistan/Mauritius were aged 40 or older; the
      youngest age profile was reported by the Australia/New Zealand/USA nurses. Two
      thirds of all the respondents indicated that a recruitment agency had been
      involved in their move to the United Kingdom (UK). Three quarters of the
      respondents (76%) reported that they were required to complete a supervised
      practice course/period of adaptation in the UK in order to be eligible to
      practice as a nurse in the UK. Two thirds (69%) of respondents were working in
      NHS hospitals in London, 13% were working in the private sector hospitals and 10%
      were working in private sector nursing homes. Most of the nurses reported they
      were the major or sole wage-earner contributing to household income. More than
      half of the respondents (57%) reported that they regularly sent remittances to
      their home country. The majority of respondents (60%) indicated that they planned
      to stay for at least five years, but just under half (43%) also reported that
      they were considering a move to another country. CONCLUSION: One critical issue
      for UK policy-makers is to determine if internationally recruited nurses will
      stay on in the UK, move back to their home country, or move on to another. That
      these nurses have made at least one international move means they are likely to
      have the propensity to move again. As such, retention efforts in the UK will have
      to take account of their career aspirations.

PMID- 16800869
TI  - Design of the New Life(style) study: a randomised controlled trial to optimise
      maternal weight development during pregnancy. [ISRCTN85313483].
AB  - BACKGROUND: Preventing excessive weight gain during pregnancy is potentially
      important in the prevention of overweight and obesity among women of childbearing
      age. However, few intervention studies aiming at weight management during
      pregnancy have been performed and most of these interventions were not as
      successful as expected. In this paper the design of the New Life(style) study is
      described as well as the content of the individually tailored intervention
      program, which focuses on controlling weight development during pregnancy.
      METHODS: The effectiveness of the New Life(style) intervention program versus
      usual care by midwives is evaluated in a randomised controlled trial. Women who
      expect their first child and visit one of the participating midwifery practices
      are included. The intervention is standardised in a protocol and executed by
      trained counsellors with the women who are randomised in the intervention group.
      During 5 sessions--at 18, 22, 30 and 36 weeks of pregnancy and at 8 weeks
      postpartum--individual weight gain is discussed in relation to weight gain
      guidelines for pregnant women of the American Institute of Medicine. Counsellors
      coach the women to maintain or optimise a healthy lifestyle, in a period of
      drastic physical and mental changes. Data is collected at 15, 25, 35 weeks of
      pregnancy and at 6, 26, and 52 weeks after delivery. Primary outcome measures are
      body weight, BMI, and skinfold thickness. Secondary outcome measures include
      physical activity, nutrition and blood levels of factors that are associated with
      energy homeostasis. DISCUSSION: Results of the current RCT will improve the
      knowledge of determinants of weight gain during pregnancy, weight retention after
      childbirth and of the effectiveness of the intervention program that is
      described. Caregivers and researchers in the field of health promotion are
      offered more insight in specific elements of the New Life(style) intervention
      program.

PMID- 16800870
TI  - Microvillous inclusion disease (microvillous atrophy).
AB  - Microvillous inclusion disease (MVID) or microvillous atrophy is a congenital
      disorder of the intestinal epithelial cells that presents with persistent life
      threatening watery diarrhea and is characterized by morphological enterocyte
      abnormalities. MVID manifests either in the first days of life (early-onset form)
      or in the first two months (late-onset form) of life. MVID is a very rare
      disorder of unknown origin, probably transmitted as an autosomal recessive trait.
      To date, no prevalence data are available. Ultrastructural analyses reveal: 1) a
      partial to total atrophy of microvilli on mature enterocytes with apical
      accumulation of numerous secretory granules in immature enterocytes; 2) the
      highly characteristic inclusion bodies containing rudimentary or fully
      differentiated microvilli in mature enterocytes. Light microscopy shows
      accumulation of PAS-positive granules at the apical pole of immature enterocytes,
      together with atrophic band indicating microvillus atrophy and, in parallel, an
      intracellular PAS or CD10 positive line (marking the microvillous inclusion
      bodies seen on electron microscopy). Intestinal failure secondary to diarrhea is
      definitive. To date, no curative therapy exists and children with MVID are
      totally dependent on parenteral nutrition. Long-term outcome is generally poor,
      due to metabolic decompensation, repeated states of dehydration, infectious and
      liver complications related to the parenteral nutrition. As MVID is a very rare
      disorder, which is extremely difficult to diagnose and manage, children with MVID
      should be transferred to specialized pediatric gastro-intestinal centers, if
      possible, a center equipped to perform small bowel transplantation. Early small
      bowel transplantation resulting in intestinal autonomy gives new hope for disease
      management and outcome.

PMID- 16800871
TI  - A comparative evaluation of pharmacy services in single and no pharmacy towns.
AB  - BACKGROUND: Recent attention has focused on access of communities to pharmacy
      services in rural areas. To increase access to pharmacy services in rural Western
      Australia some doctors have been granted a licence to dispense medication on the
      rationale that a pharmacy would not be economically viable in that community.
      However, there have been no studies conducted on whether a doctor dispensing
      service adequately provides a pharmacy service with respect to access and
      quality. METHOD: Residents of seven single pharmacy towns and seven non-pharmacy
      rural towns were surveyed to evaluate pharmacy services delivered by a pharmacist
      and doctor. The towns were chosen to match closely on key demographic features,
      with an average population of 1,246 and 1,263 respectively. A random sample of
      150 households from each town was sent the questionnaire on pharmacy services
      (1050 in each group). Data was also collected from the Health Insurance
      Commission (HIC) on dispensing locations for the residents of the two groups of
      towns. RESULTS: There was a significant difference in access to pharmacy services
      with 82.4% of participants from pharmacy towns accessing medications within their
      town compared to 51.3% of non-pharmacy town participants. The HIC data supported
      these trends with pharmacy town residents having relatively higher prescription
      rates within their town compared to non-pharmacy town residents where they were
      more likely to access prescriptions out of their town. CONCLUSION: Pharmacy town
      participants were more satisfied with access to health and pharmacy services
      within their town. Continuation of the doctor dispensing policy requires a
      greater consideration of the pharmacy needs of rural residents.

PMID- 16800872
TI  - The visible touch: in planta visualization of protein-protein interactions by
      fluorophore-based methods.
AB  - Non-invasive fluorophore-based protein interaction assays like fluorescence
      resonance energy transfer (FRET) and bimolecular fluorescence complementation
      (BiFC, also referred to as "split YFP") have been proven invaluable tools to
      study protein-protein interactions in living cells. Both methods are now
      frequently used in the plant sciences and are likely to develop into standard
      techniques for the identification, verification and in-depth analysis of
      polypeptide interactions. In this review, we address the individual strengths and
      weaknesses of both approaches and provide an outlook about new directions and
      possible future developments for both techniques.

PMID- 16800874
TI  - Zinc, oxidative stress, genetic background and immunosenescence: implications for
      healthy ageing.
AB  - The relevance of zinc for proper functioning of the entire immune system is
      already well documented. However, the identification of individuals who really
      need zinc supplementation is still debated in view of the fact that excessive
      zinc may also be toxic. The risk of developing zinc deficiency in people from
      industrialized countries is relatively low, except for elderly subjects where
      zinc intake may be suboptimal and inflammation is chronic. Thus, the role of zinc
      on the immune system and on the health of European elderly people is becoming of
      paramount importance, considering also that the elderly population is rapidly
      increasing. In particular, the factors contributing to and the biochemical
      markers of zinc deficiency in the elderly are still remain to be established.
      Epidemiological, functional, and genetic studies aimed at formulating a rationale
      for the promotion of healthy ageing through zinc supplementation was the subject
      of an International Conference held in Madrid from 11-13 February 2006 (3rd
      ZincAge Meeting) at the CNIO Institute (local organizer: Maria Blasco, partner of
      ZincAge).

PMID- 16800873
TI  - Cytokine response to lipoprotein lipid loading in human monocyte-derived
      macrophages.
AB  - BACKGROUND: Macrophage foam cell formation is a prominent feature of human
      atherosclerotic plaques, usually considered to be correlated to uptake of and
      inflammatory response to oxidized low density lipoproteins (OxLDL). However,
      there are alternative pathways for formation of macrophage foam cells and the
      effect of such lipid loading on macrophage function remains to be fully
      characterized. In the present study we investigated basal and inducible cytokine
      expression in primary human macrophages either loaded with triglycerides through
      incubation with very low density lipoproteins (VLDL) or with cholesterol through
      incubation with aggregated LDL (AgLDL). We then analyzed how foam cell lipid
      content affected secretion of three pro-inflammatory cytokines: interleukin-1beta
      (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and
      of one chemokine: interleukin-8 (IL-8), all of which are considered pro
      inflammatory, pro-atherosclerotic, and are expressed by cells in atherosclerotic
      tissue. RESULTS: Formation of triglyceride-loaded foam cells resulted in a four
      fold increase in basal IL-1beta secretion, whereas cholesterol loading lacked
      significant effect on IL-1beta secretion. In contrast, secretion of TNF-alpha and
      IL-6 decreased significantly following both cholesterol and triglyceride loading,
      with a similar trend for secretion of IL-8. Lipid loading did not affect cell
      viability or expression of caspase-3, and did not significantly affect macrophage
      ability to respond to stimulation with exogenous TNF-alpha. CONCLUSION: Lipid
      loading of primary human macrophages resulted in altered cytokine secretion from
      cells, where effects were similar regardless of neutral lipid composition of
      cells. The exception was IL-1beta, where triglyceride, but not cholesterol, lipid
      loading resulted in a stimulation of basal secretion of the cytokine. It is
      apparent that macrophage cytokine secretion is affected by lipid loading by
      lipoproteins other than OxLDL. As both VLDL and AgLDL have been found in the
      vessel wall, macrophage cytokine response to uptake of these lipoproteins may
      have a direct effect on atherosclerotic development in vivo. However, macrophage
      neutral lipid amount and composition did not affect cellular activation by
      exogenous TNF-alpha, making it likely that lipoprotein lipid loading can affect
      foam cell cytokine secretion during basal conditions but that the effects can be
      overruled by TNF-alpha during acute inflammation.

PMID- 16800875
TI  - Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis.
AB  - BACKGROUND: Detecting serum antibody against inhaled antigens is an important
      diagnostic adjunct for hypersensitivity pneumonitis (HP). We sought to validate a
      quantitative fluorimetric assay testing serum from bird fanciers. METHODS:
      Antibody activity was assessed in bird fanciers and control subjects using
      various avian antigens and serological methods, and the titer was compared with
      symptoms of HP. RESULTS: IgG antibody against pigeon serum antigens, quantified
      by fluorimetry, provided a good discriminator of disease. Levels below 10 mg/L
      were insignificant, and increasing titers were associated with disease. The assay
      was unaffected by total IgG, autoantibodies and antibody to dietary hen's egg
      antigens. Antigens from pigeon serum seem sufficient to recognize immune
      sensitivity to most common pet avian species. Decreasing antibody titers
      confirmed antigen avoidance. CONCLUSION: Increasing antibody titer reflected the
      likelihood of HP, and decreasing titers confirmed antigen avoidance. Quantifying
      antibody was rapid and the increased sensitivity will improve the rate of false
      negative reporting and obviate the need for invasive diagnostic procedures.
      Automated fluorimetry provides a method for the international standardization of
      HP serology thereby improving quality control and improving its suitability as a
      diagnostic adjunct.

PMID- 16800876
TI  - Metabolic engineering of potato tuber carotenoids through tuber-specific
      silencing of lycopene epsilon cyclase.
AB  - BACKGROUND: Potato is a major staple food, and modification of its provitamin
      content is a possible means for alleviating nutritional deficiencies. beta
      carotene is the main dietary precursor of vitamin A. Potato tubers contain low
      levels of carotenoids, composed mainly of the xanthophylls lutein,
      antheraxanthin, violaxanthin, and of xanthophyll esters. None of these
      carotenoids have provitamin A activity. RESULTS: We silenced the first dedicated
      step in the beta-epsilon- branch of carotenoid biosynthesis, lycopene epsilon
      cyclase (LCY-e), by introducing, via Agrobacterium-mediated transformation, an
      antisense fragment of this gene under the control of the patatin promoter. Real
      Time measurements confirmed the tuber-specific silencing of Lcy-e. Antisense
      tubers showed significant increases in beta-beta-carotenoid levels, with beta
      carotene showing the maximum increase (up to 14-fold). Total carotenoids
      increased up to 2.5-fold. These changes were not accompanied by a decrease in
      lutein, suggesting that LCY-e is not rate-limiting for lutein accumulation. Tuber
      specific changes in expression of several genes in the pathway were observed.
      CONCLUSION: The data suggest that epsilon-cyclization of lycopene is a key
      regulatory step in potato tuber carotenogenesis. Upon tuber-specific silencing of
      the corresponding gene, beta-beta-carotenoid and total carotenoid levels are
      increased, and expression of several other genes in the pathway is modified.

PMID- 16800877
TI  - Highly variable sperm precedence in the stalk-eyed fly, Teleopsis dalmanni.
AB  - BACKGROUND: When females mate with different males, competition for
      fertilizations occurs after insemination. Such sperm competition is usually
      summarized at the level of the population or species by the parameter, P2,
      defined as the proportion of offspring sired by the second male in double mating
      trials. However, considerable variation in P2 may occur within populations, and
      such variation limits the utility of population-wide or species P2 estimates as
      descriptors of sperm usage. To fully understand the causes and consequences of
      sperm competition requires estimates of not only mean P2, but also intra-specific
      variation in P2. Here we investigate within-population quantitative variation in
      P2 using a controlled mating experiment and microsatellite profiling of progeny
      in the multiply mating stalk-eyed fly, Teleopsis dalmanni. RESULTS: We genotyped
      381 offspring from 22 dam-sire pair families at four microsatellite loci. The
      mean population-wide P2 value of 0.40 was not significantly different from that
      expected under random sperm mixing (i.e. P2 = 0.5). However, patterns of
      paternity were highly variable between individual families; almost half of
      families displayed extreme second male biases resulting in zero or complete
      paternity, whereas only about one third of families had P2 values of 0.5, the
      remainder had significant, but moderate, paternity skew. CONCLUSION: Our data
      suggest that all modes of ejaculate competition, from extreme sperm precedence to
      complete sperm mixing, occur in T. dalmanni. Thus the population mean P2 value
      does not reflect the high underlying variance in familial P2. We discuss some of
      the potential causes and consequences of post-copulatory sexual selection in this
      important model species.

PMID- 16800878
TI  - A rare differential diagnosis to occupational neck pain: bilateral stylohyoid
      syndrome.
AB  - Chronic neck pain is widely prevalent and a common source of disability in the
      working-age population. Etiology of chronic neck pain includes neck sprain,
      mechanical or muscular neck pain, myofascial pain syndrome, postural neck pain as
      well as pain due to degenerative changes. We report the case of a 42 year old
      secretary, complaining about a longer history of neck pain and limited movement
      of the cervical spine. Surprisingly, the adequate radiologic examination revealed
      a bilateral ossification of the stylohyoid ligament complex. Her symptoms
      remained intractable from conservative treatment consisting of anti-inflammatory
      medication as well as physical therapy. Hence the patient was admitted to
      surgical resection of the ossified stylohyoid ligament complex. Afterwards she
      was free of any complaints and went back to work. Therefore, ossification of the
      stylohyoid ligament complex causing severe neck pain and movement disorder should
      be regarded as a rare differential diagnosis of occupational related neck pain.

PMID- 16800879
TI  - Adhesive properties of Enterobacter sakazakii to human epithelial and brain
      microvascular endothelial cells.
AB  - BACKGROUND: Enterobacter sakazakii is an opportunistic pathogen that has been
      associated with sporadic cases and outbreaks causing meningitis, necrotizing
      enterocolitis and sepsis especially in neonates. However, up to now little is
      known about the mechanisms of pathogenicity in E. sakazakii. A necessary state in
      the successful colonization, establishment and ultimately production of disease
      by microbial pathogens is the ability to adhere to host surfaces such as mucous
      membranes, gastric and intestinal epithelial or endothelial tissue. This study
      examined for the first time the adherence ability of 50 E. sakazakii strains to
      the two epithelial cell lines HEp-2 and Caco-2, as well as the brain
      microvascular endothelial cell line HBMEC. Furthermore, the effects of bacterial
      culture conditions on the adherence behaviour were investigated. An attempt was
      made to characterize the factors involved in adherence. RESULTS: Two distinctive
      adherence patterns, a diffuse adhesion and the formation of localized clusters of
      bacteria on the cell surface could be distinguished on all three cell lines. In
      some strains, a mixture of both patterns was observed. Adherence was maximal
      during late exponential phase, and increased with higher MOI. The adhesion
      capacity of E. sakazakii to HBMEC cells was affected by the addition of blood to
      the bacteria growth medium. Mannose, hemagglutination, trypsin digestion
      experiments and transmission electron microscopy suggested that the adhesion of
      E. sakazakii to the epithelial and endothelial cells is mainly non-fimbrial
      based. CONCLUSION: Adherence experiments show heterogeneity within different E.
      sakazakii strains. In agreement with studies on E. cloacae, we found no
      relationship between the adhesive capacities in E. sakazakii and the eventual
      production of specific fimbriae. Further studies will have to be carried out in
      order to determine the adhesin(s) involved in the interaction of E. sakazakii
      with cells and to enhance knowledge of the pathogenesis of E. sakazakii
      infection.

PMID- 16800880
TI  - The effect of imposing a higher, uniform tobacco tax in Vietnam.

PMID- 16800881
TI  - Place-of-residence errors on death certificates for two contiguous U. S.
      counties.
AB  - BACKGROUND: Based on death certificate data, the Texas Department of Health
      Bureau of Vital Statistics calculates age adjusted all-cause mortality rates for
      each Texas county yearly. In 1998 the calculated rates for two adjacent Texas
      counties was disparate. These counties contain one city (Amarillo) and are
      identical in size. This study examined the accuracy of recorded county of
      residence for deaths in the two counties in 1998. In our jurisdiction, the county
      of residence is assigned by funeral homes. METHODS: A random sample of 20% of
      death certificates was selected. The accuracy of the county of residence was
      verified by using a large area map, Tax Appraisal District records, and U.S.
      Census Bureau databases. Inaccuracies in recording the county or zip code of
      residence was recorded. RESULTS: Eighteen of 354 (5.4%) death certificates
      recorded the incorrect county and 21 of 354 (5.9%) of death certificates recorded
      the zip code improperly. There was a 14.4% county recording error rate for one
      county compared to a 0.82% for the other county. The zip code error rate was
      similar for the two counties (5.9% vs. 5.8%). Of the county errors, 83% occurred
      for addresses within a zip code that contained addresses in both counties.
      CONCLUSION: This study demonstrated a large error rate (14%) in recording county
      of residence for deaths in one county. A similar rate was not seen in an adjacent
      county. This led to significant miscalculation of mortality rates for two
      counties. We believe that errors may have arisen in part from use of internet
      programs by funeral homes to assign the county of residence. With some of these
      programs, the county is determined by zip code, and when a zip code straddles two
      counties, the program automatically assigns the county whose name appears first
      in the alphabet. This type of error could be avoided if funeral homes determined
      the county of residence from Tax Appraisal District or Census Bureau records,
      both of which are available on the internet. This type of error could also be
      avoided if vital statistics offices verified the county and zip code of residence
      using official sources.

PMID- 16800882
TI  - Distinct expression profiles of TGF-beta1 signaling mediators in pathogenic
      SIVmac and non-pathogenic SIVagm infections.
AB  - BACKGROUND: The generalized T-cell activation characterizing HIV-1 and SIVmac
      infections in humans and macaques (MACs) is not found in the non-pathogenic
      SIVagm infection in African green monkeys (AGMs). We have previously shown that
      TGF-beta1, Foxp3 and IL-10 are induced very early after SIVagm infection. In
      SIVmac-infected MACs, plasma TGF-beta1 induction persists during primary
      infection 1. We raised the hypothesis that MACs are unable to respond to TGF
      beta1 and thus cannot resorb virus-driven inflammation. We therefore compared the
      very early expression dynamics of pro- and anti-inflammatory markers as well as
      of factors involved in the TGF-beta1 signaling pathway in SIV-infected AGMs and
      MACs. METHODS: Levels of transcripts encoding for pro- and anti-inflammatory
      markers (tnf-alpha, ifn-gamma, il-10, t-bet, gata-3) as well as for TGF-beta1
      signaling mediators (smad3, smad4, smad7) were followed by real time PCR in a
      prospective study enrolling 6 AGMs and 6 MACs. RESULTS: During primary SIVmac
      infection, up-regulations of tnf-alpha, ifn-gamma and t-bet responses (days 1-16
      p.i.) were stronger whereas il-10 response was delayed (4th week p.i.) compared
      to SIVagm infection. Up-regulation of smad7 (days 3-8 p.i.), a cellular mediator
      inhibiting the TGF-beta1 signaling cascade, characterized SIV-infected MACs. In
      AGMs, we found increases of gata-3 but not t-bet, a longer lasting up-regulation
      of smad4 (days 1-21 p.i), a mediator enhancing TGF-beta1 signaling, and no smad7
      up-regulations. CONCLUSION: Our data suggest that the inability to resorb virus
      driven inflammation and activation during the pathogenic HIV-1/SIVmac infections
      is associated with an unresponsiveness to TGF-beta1.

PMID- 16800883
TI  - Nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that
      cover the surface and line the nasopharynx. The annual incidence of NPC in the UK
      is 0.3 per million at age 0-14 years, and 1 to 2 per million at age 15-19 years.
      Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC
      accounts for about one third of childhood nasopharyngeal neoplasms. Three
      subtypes of NPC are recognized in the World Health Organization (WHO)
      classification: 1) squamous cell carcinoma, typically found in the older adult
      population; 2) non-keratinizing carcinoma; 3) undifferentiated carcinoma. The
      tumor can extend within or out of the nasopharynx to the other lateral wall
      and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or
      oropharynx. It then typically metastases to cervical lymph nodes. Cervical
      lymphadenopathy is the initial presentation in many patients, and the diagnosis
      of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor
      include trismus, pain, otitis media, nasal regurgitation due to paresis of the
      soft palate, hearing loss and cranial nerve palsies. Larger growths may produce
      nasal obstruction or bleeding and a "nasal twang". Etiological factors include
      Epstein-Barr virus (EBV), genetic susceptibility and consumption of food with
      possible carcinogens--volatile nitrosamines. The recommended treatment schedule
      consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant
      interferon (IFN)-beta therapy.

PMID- 16800884
TI  - Genetic modification and genetic determinism.
AB  - In this article we examine four objections to the genetic modification of human
      beings: the freedom argument, the giftedness argument, the authenticity argument,
      and the uniqueness argument. We then demonstrate that each of these arguments
      against genetic modification assumes a strong version of genetic determinism.
      Since these strong deterministic assumptions are false, the arguments against
      genetic modification, which assume and depend upon these assumptions, are
      therefore unsound. Serious discussion of the morality of genetic modification,
      and the development of sound science policy, should be driven by arguments that
      address the actual consequences of genetic modification for individuals and
      society, not by ones propped up by false or misleading biological assumptions.

PMID- 16800885
TI  - Deviation of eyes and head in acute cerebral stroke.
AB  - BACKGROUND: It is a well-known phenomenon that some patients with acute left or
      right hemisphere stroke show a deviation of the eyes (Prevost's sign) and head to
      one side. Here we investigated whether both right- and left-sided brain lesions
      may cause this deviation. Moreover, we studied the relationship between this
      phenomenon and spatial neglect. In contrast to previous studies, we determined
      not only the discrete presence or absence of eye deviation with the naked eye
      through clinical inspection, but actually measured the extent of horizontal eye
      in-head and head-on-trunk deviation. In further contrast, measurements were
      performed early after stroke onset (1.5 days on average). METHODS: Eye-in-head
      and head-on-trunk positions were measured at the bedside in 33 patients with
      acute unilateral left or right cerebral stroke consecutively admitted to our
      stroke unit. RESULTS: Each single patient with spatial neglect and right
      hemisphere lesion showed a marked deviation of the eyes and the head to the
      ipsilesional, right side. The average spontaneous gaze position in this group was
      46 degrees right, while it was close to the saggital body midline (0 degrees ) in
      the groups with acute left- or right-sided stroke but no spatial neglect as well
      as in healthy subjects. CONCLUSION: A marked horizontal eye and head deviation
      observed approximately 1.5 days post-stroke is not a symptom associated with
      acute cerebral lesions per se, nor is a general symptom of right hemisphere
      lesions, but rather is specific for stroke patients with spatial neglect. The
      evaluation of the patient's horizontal eye and head position thus could serve as
      a brief and easy way helping to diagnose spatial neglect, in addition to the
      traditional paper-and-pencil tests.

PMID- 16800886
TI  - Cancer during pregnancy alters the activity of rat placenta and enhances the
      expression of cleaved PARP, cytochrome-c and caspase 3.
AB  - BACKGROUND: The presence of cancer makes it difficult to predict the progress of
      pregnancy and can be deleterious to the maternal-foetal relationship. Apoptosis
      may affect a range of placental functions and result in the retardation of foetal
      growth. In this work, we investigated the placental alterations produced by
      tumour growth and the effects on the expression of apoptotic factors in placental
      tissue. METHODS: Adult female Wistar rats (90 days old, n = 54) were allocated to
      control (C), tumour-bearing (W), or ascitic fluid-injected (A) groups and were
      killed on the 16th, 19th or 21st day of pregnancy. Placental tissues were
      analysed using biochemical and histochemical assays. RESULTS: The placental
      protein content and glutathione-S-transferase activity were decreased in groups W
      and A. Histochemical analysis showed an increase in the number of cells with
      cleaved PARP, caspase 3 and cytochrome-c in groups W and A, indicating that the
      tumour growth clearly damaged placental tissue and affected the levels of
      apoptotic factors. These results were confirmed by western blotting. CONCLUSION:
      Since trophoblastic cells are responsible for maintaining a normal placental
      function, the uncontrolled death of these cells in response to tumour cell growth
      or substances derived from ascitic fluid could have a negative impact on foetal
      development. Further knowledge of these events may help to preserve the foetus
      and placenta during development.

PMID- 16800887
TI  - Characterization of the minimum domain required for targeting budding yeast
      myosin II to the site of cell division.
AB  - BACKGROUND: All eukaryotes with the exception of plants use an actomyosin ring to
      generate a constriction force at the site of cell division (cleavage furrow)
      during mitosis and meiosis. The structure and filament forming abilities located
      in the C-terminal or tail region of one of the main components, myosin II, are
      important for localising the molecule to the contractile ring (CR) during
      cytokinesis. However, it remains poorly understood how myosin II is recruited to
      the site of cell division and how this recruitment relates to myosin filament
      assembly. Significant conservation between species of the components involved in
      cytokinesis, including those of the CR, allows the use of easily genetically
      manipulated organisms, such as budding yeast (Saccharomyces cerevisiae), in the
      study of cytokinesis. Budding yeast has a single myosin II protein, named Myo1.
      Unlike most other class II myosins, the tail of Myo1 has an irregular coiled
      coil. In this report we use molecular genetics, biochemistry and live cell
      imaging to characterize the minimum localisation domain (MLD) of budding yeast
      Myo1. RESULTS: We show that the MLD is a small region in the centre of the tail
      of Myo1 and that it is both necessary and sufficient for localisation of Myo1 to
      the yeast bud neck, the pre-determined site of cell division. Hydrodynamic
      measurements of the MLD, purified from bacteria or yeast, show that it is likely
      to exist as a trimer. We also examine the importance of a small region of low
      coiled coil forming probability within the MLD, which we call the hinge region.
      Removal of the hinge region prevents contraction of the CR. Using fluorescence
      recovery after photobleaching (FRAP), we show that GFP-tagged MLD is slightly
      more dynamic than the GFP-tagged full length molecule but less dynamic than the
      GFP-tagged Myo1 construct lacking the hinge region. CONCLUSION: Our results
      define the intrinsic determinant for the localization of budding yeast myosin II
      and show it to be an oligomer of tentatively 3 monomers. We suggest that this is
      the minimum oligomeric unit (rather than the traditional myosin II dimer) that
      would allow specific assembly to the site of cytokinesis in a manner similar to
      the full length molecule. The flexible hinge region also contributes to CR
      structural integrity and contractility.

PMID- 16800888
TI  - Clustering of Pseudomonas aeruginosa transcriptomes from planktonic cultures,
      developing and mature biofilms reveals distinct expression profiles.
AB  - BACKGROUND: Pseudomonas aeruginosa is a genetically complex bacterium which can
      adopt and switch between a free-living or biofilm lifestyle, a versatility that
      enables it to thrive in many different environments and contributes to its
      success as a human pathogen. RESULTS: Transcriptomes derived from growth states
      relevant to the lifestyle of P. aeruginosa were clustered using three different
      methods (K-means, K-means spectral and hierarchical clustering). The culture
      conditions used for this study were; biofilms incubated for 8, 14, 24 and 48 hrs,
      and planktonic culture (logarithmic and stationary phase). This cluster analysis
      revealed the existence and provided a clear illustration of distinct expression
      profiles present in the dataset. Moreover, it gave an insight into which genes
      are up-regulated in planktonic, developing biofilm and confluent biofilm states.
      In addition, this analysis confirmed the contribution of quorum sensing (QS) and
      RpoS regulated genes to the biofilm mode of growth, and enabled the
      identification of a 60.69 Kbp region of the genome associated with stationary
      phase growth (stationary phase planktonic culture and confluent biofilms).
      CONCLUSION: This is the first study to use clustering to separate a large P.
      aeruginosa microarray dataset consisting of transcriptomes obtained from diverse
      conditions relevant to its growth, into different expression profiles. These
      distinct expression profiles not only reveal novel aspects of P. aeruginosa gene
      expression but also provide a growth specific transcriptomic reference dataset
      for the research community.

PMID- 16800889
TI  - Splenic peliosis with spontaneous splenic rupture: report of two cases.
AB  - BACKGROUND: Peliosis is a rare condition characterised by multiple cyst-like,
      blood-filled cavities within the parenchyma of solid organs. Most commonly
      affecting the liver, isolated splenic peliosis is an even more unique phenomenon.
      Patients with the condition are often asymptomatic. However, this potentially
      lethal condition can present with spontaneous organ rupture. We present two such
      cases, discuss their management and review what is currently known in the
      existing literature. CASE PRESENTATION: A previously well twenty-six year old
      woman presented with abdominal pain following a trivial episode of coughing. A
      diagnosis of spontaneous splenic rupture was made following clinical and
      radiological examination. She underwent emergency splenectomy and made a full,
      uneventful recovery. Histopathological examination confirmed splenic peliosis.
      The second case describes an eighty six year old lady who sustained a trivial
      fall and developed pain in her left side. A CT confirmed splenic rupture. She
      became haemodynamically unstable during her admission and underwent emergency
      splenectomy. Histopathological examination revealed splenic peliosis. She went on
      to make an uneventful recovery. CONCLUSION: Splenic peliosis is very rare. It has
      a number of associations including immunosuppression, drug therapy and infection.
      Although patients are often asymptomatic, life-threatening spontaneous organ
      rupture may occur. If the diagnosis of peliosis is confirmed, additional
      investigations should be considered to detect its presence in other organs.
      Furthermore, the presence of the condition may be relevant if further medical or
      surgical intervention is planned.

PMID- 16800890
TI  - The paradoxical effects of splenectomy on tumor growth.
AB  - BACKGROUND: There is a vast and contradictory literature concerning the effect of
      the spleen and particularly of splenectomy on tumor growth. Sometimes splenectomy
      seems to inhibit tumor growth, but in other cases it seems, paradoxically, to
      facilitate both oncogenesis and the growth of established tumors. APPROACH: In
      this essay I have selected from this large literature a few papers that seem
      particularly instructive, in the hope of extracting some understanding of the
      rules governing this paradoxical behavior. CONCLUSION: In general, whether
      splenectomy enhances or inhibits tumor growth seems to depend primarily upon the
      ratio of spleen to tumor. Small proportions of spleen cells usually stimulate
      tumor growth, in which case splenectomy is inhibitory. Larger proportions of the
      same cells, especially if they are from immunized animals, usually inhibit tumor
      growth, in which case splenectomy results in tumor stimulation.

PMID- 16800891
TI  - A general method for the unbiased improvement of solution NMR structures by the
      use of related X-ray data, the AUREMOL-ISIC algorithm.
AB  - BACKGROUND: Rapid and accurate three-dimensional structure determination of
      biological macromolecules is mandatory to keep up with the vast progress made in
      the identification of primary sequence information. During the last few years the
      amount of data deposited in the protein data bank has substantially increased
      providing additional information for novel structure determination projects. The
      key question is how to combine the available database information with the
      experimental data of the current project ensuring that only relevant information
      is used and a correct structural bias is produced. For this purpose a novel fully
      automated algorithm based on Bayesian reasoning has been developed. It allows the
      combination of structural information from different sources in a consistent way
      to obtain high quality structures with a limited set of experimental data. The
      new ISIC (Intelligent Structural Information Combination) algorithm is part of
      the larger AUREMOL software package. RESULTS: Our new approach was successfully
      tested on the improvement of the solution NMR structures of the Ras-binding
      domain of Byr2 from Schizosaccharomyces pombe, the Ras-binding domain of RalGDS
      from human calculated from a limited set of NMR data, and the immunoglobulin
      binding domain from protein G from Streptococcus by their corresponding X-ray
      structures. In all test cases clearly improved structures were obtained. The
      largest danger in using data from other sources is a possible bias towards the
      added structure. In the worst case instead of a refined target structure the
      structure from the additional source is essentially reproduced. We could clearly
      show that the ISIC algorithm treats these difficulties properly. CONCLUSION: In
      summary, we present a novel fully automated method to combine strongly coupled
      knowledge from different sources. The combination with validation tools such as
      the calculation of NMR R-factors strengthens the impact of the method
      considerably since the improvement of the structures can be assessed
      quantitatively. The ISIC method can be applied to a large number of similar
      problems where the quality of the obtained three-dimensional structures is
      limited by the available experimental data like the improvement of large NMR
      structures calculated from sparse experimental data or the refinement of low
      resolution X-ray structures. Also structures may be refined using other available
      structural information such as homology models.

PMID- 16800892
TI  - Conditional gene expression in the mouse using a Sleeping Beauty gene-trap
      transposon.
AB  - BACKGROUND: Insertional mutagenesis techniques with transposable elements have
      been popular among geneticists studying model organisms from E. coli to
      Drosophila and, more recently, the mouse. One such element is the Sleeping Beauty
      (SB) transposon that has been shown in several studies to be an effective
      insertional mutagen in the mouse germline. SB transposon vector studies have
      employed different functional elements and reporter molecules to disrupt and
      report the expression of endogenous mouse genes. We sought to generate a
      transposon system that would be capable of reporting the expression pattern of a
      mouse gene while allowing for conditional expression of a gene of interest in a
      tissue- or temporal-specific pattern. RESULTS: Here we report the systematic
      development and testing of a transposon-based gene-trap system incorporating the
      doxycycline-repressible Tet-Off (tTA) system that is capable of activating the
      expression of genes under control of a Tet response element (TRE) promoter. We
      demonstrate that the gene trap system is fully functional in vitro by introducing
      the "gene-trap tTA" vector into human cells by transposition and identifying
      clones that activate expression of a TRE-luciferase transgene in a doxycycline
      dependent manner. In transgenic mice, we mobilize gene-trap tTA vectors, discover
      parameters that can affect germline mobilization rates, and identify candidate
      gene insertions to demonstrate the in vivo functionality of the vector system. We
      further demonstrate that the gene-trap can act as a reporter of endogenous gene
      expression and it can be coupled with bioluminescent imaging to identify genes
      with tissue-specific expression patterns. CONCLUSION: Akin to the GAL4/UAS system
      used in the fly, we have made progress developing a tool for mutating and
      revealing the expression of mouse genes by generating the tTA transactivator in
      the presence of a secondary TRE-regulated reporter molecule. A vector like the
      gene-trap tTA could provide a means for both annotating mouse genes and creating
      a resource of mice that express a regulable transcription factor in temporally-
      and tissue-specific patterns for conditional gene expression studies. These mice
      would be a valuable resource to the mouse genetics community for purpose of
      dissecting mammalian gene function.

PMID- 16800893
TI  - Liver metastases of neuroendocrine tumours; early reduction of tumour load to
      improve life expectancy.
AB  - BACKGROUND: Neuroendocrine tumours frequently metastasize to the liver. Although
      generally slowly progressing, hepatic metastases are the major cause of carcinoid
      syndrome and ultimately lead to liver dysfunction, cardiac insufficiency and
      finally death. METHODS: A literature review was performed to define the optimal
      treatment strategy and work-up in patients with neuroendocrine hepatic
      metastases. Based on this, an algorithm for the management of these patients was
      established. RESULTS: Platelet serotonin and chromogranin A are useful biomarkers
      for detection and follow-up of neuroendocrine tumour. Helical computed tomography
      and somatostatin receptor scintigraphy are the most sensitive diagnostic
      modalities. Surgical debulking is an accepted approach for reducing hormonal
      symptoms and to establish better conditions for medical treatment, but is
      frequently impossible due to the extent of disease. A novel approach is the local
      ablation of tumour by thermal coagulation using therapies such as radiofrequency
      ablation (RFA) or laser induced thermotherapy (LITT). These techniques preserve
      normal liver tissue. There is a tendency to destroy metastases early in the
      course of disease, thereby postponing or eliminating the surgically untreatable
      stage. This can be combined with postoperative radioactive octreotide to
      eliminate small multiple metastases. In patients with extensive metastases who
      are not suitable for local destruction, systemic therapy by octreotide, 131I-MIBG
      treatment or targeted chemo- and radiotherapy should be attempted. A final option
      for selective patients is orthotopic liver transplantation. CONCLUSION: Treatment
      for patients with neuroendocrine hepatic metastases must be tailored for each
      individual patient. When local ablative therapies are used early in the course of
      the disease, the occurrence of carcinoid syndrome with end stage hepatic disease
      can be postponed or prevented.

PMID- 16800894
TI  - Wild-type and central DNA flap defective HIV-1 lentiviral vector genomes:
      intracellular visualization at ultrastructural resolution levels.
AB  - HIV-1 and other lentiviruses have the unique ability among retroviruses to
      efficiently replicate in non-dividing cells as a result of the active nuclear
      import of their DNA genome across an interphasic nuclear membrane. Previous work
      has shown that a three-stranded DNA structure synthesized during HIV-1 reverse
      transcription, called the central DNA flap, acts as a cis-determinant of HIV-1
      genome nuclear import. Concordantly, DNA Flap re-insertion in lentiviral-derived
      gene therapy vectors stimulates gene transfer efficiencies and complements the
      level of nuclear import to wild-type levels quantitatively indistinguishable from
      wild-type virus in all cell types and tissues examined so far. In order to define
      the precise nature of the replicative defect of DNA flap mutant viruses, we
      carried out in situ DNA hybridization experiments with electron microscopy to
      determine the subcellular localization of DNA flap mutant and wild-type HIV-1
      genomes. We found that Flap defective DNA genomes accumulate at the cytoplasmic
      face of the nuclear membrane with no overlap across the nuclear membrane, whereas
      wild-type genomes localize throughout the nuclear compartment. These data provide
      an unequivocal confirmation of the role of the DNA flap in HIV-1 nuclear import
      and further establish that the DNA flap controls a step that immediately precedes
      translocation through the nuclear pore. Further, the widespread distribution of
      wild-type genomes within the open chromatin confirms the recent genome-wide
      mapping of HIV-1 cDNA integration sites and points to an as-yet poorly understood
      step of intranuclear transport of HIV-1 pre-integration complexes.

PMID- 16800895
TI  - Prospective screening study of 0.5 Tesla dedicated magnetic resonance imaging for
      the detection of breast cancer in young, high-risk women.
AB  - BACKGROUND: Evidence-based screening guidelines are needed for women under 40
      with a family history of breast cancer, a BRCA1 or BRCA2 mutation, or other risk
      factors. An accurate assessment of breast cancer risk is required to balance the
      benefits and risks of surveillance, yet published studies have used narrow risk
      assessment schemata for enrollment. Breast density limits the sensitivity of film
      screen mammography but is not thought to pose a limitation to MRI, however the
      utility of MRI surveillance has not been specifically examined before in women
      with dense breasts. Also, all MRI surveillance studies yet reported have used
      high strength magnets that may not be practical for dedicated imaging in many
      breast centers. Medium strength 0.5 Tesla MRI may provide an alternative economic
      option for surveillance. METHODS: We conducted a prospective, nonrandomized pilot
      study of 30 women age 25-49 years with dense breasts evaluating the addition of
      0.5 Tesla MRI to conventional screening. All participants had a high quantitative
      breast cancer risk, defined as > or = 3.5% over the next 5 years per the Gail or
      BRCAPRO models, and/or a known BRCA1 or BRCA2 germline mutation. RESULTS: The
      average age at enrollment was 41.4 years and the average 5-year risk was 4.8%.
      Twenty-two subjects had BIRADS category 1 or 2 breast MRIs (negative or probably
      benign), whereas no category 4 or 5 MRIs (possibly or probably malignant) were
      observed. Eight subjects had BIRADS 3 results, identifying lesions that were
      "probably benign", yet prompting further evaluation. One of these subjects was
      diagnosed with a stage T1aN0M0 invasive ductal carcinoma, and later determined to
      be a BRCA1 mutation carrier. CONCLUSION: Using medium-strength MRI we were able
      to detect 1 early breast tumor that was mammographically undetectable among 30
      young high-risk women with dense breasts. These results support the concept that
      breast MRI can enhance surveillance for young high-risk women with dense breasts,
      and further suggest that a medium-strength instrument is sufficient for this
      application. For the first time, we demonstrate the use of quantitative breast
      cancer risk assessment via a combination of the Gail and BRCAPRO models for
      enrollment in a screening trial.

PMID- 16800896
TI  - Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor
      density and electrical activation pattern in a rabbit model of non-ischemic heart
      failure.
AB  - BACKGROUND: Since only little is known on stem cell therapy in non-ischemic heart
      failure we wanted to know whether a long-term improvement of cardiac function in
      non-ischemic heart failure can be achieved by stem cell transplantation. METHODS:
      White male New Zealand rabbits were treated with doxorubicin (3 mg/kg/week; 6
      weeks) to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained
      autologous bone marrow stem cells (BMSC) and injected 1.5-2.0 Mio cells in 1 ml
      medium by infiltrating the myocardium via a left anterolateral thoracotomy in
      comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was
      determined in-vivo using a Millar catheter. Thereafter, the heart was excised and
      processed for radioligand binding assays to detect beta1- and beta2-adrenoceptor
      density. In addition, catecholamine plasma levels were determined via HPLC. In a
      subgroup we investigated cardiac electrophysiology by use of 256 channel mapping.
      RESULTS: In doxorubicin-treated animals beta-adrenoceptor density was
      significantly down-regulated in left ventricle and septum, but not in right
      ventricle, thereby indicating a typical left ventricular heart failure. Sham
      operated rabbits exhibited the same down-regulation. In contrast, BMSC
      transplantation led to significantly less beta-adrenoceptor down-regulation in
      septum and left ventricle. Cardiac contractility was significantly decreased in
      heart failure and sham-operated rabbits, but was significantly higher in BMSC
      transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced
      in heart failure and sham-operated animals, while these were not different from
      normal in BMSC-transplanted animals. Electrophysiological mapping revealed
      unaltered electrophysiology and did not show signs of arrhythmogeneity.
      CONCLUSION: BMSC transplantation improves sympathoadrenal dysregulation in non
      ischemic heart failure.

PMID- 16800898
TI  - Tuberculous abdominal cocoon--a report of 6 cases and review of the Literature.
AB  - The abdominal cocoon is a rare cause of intestinal obstruction that is usually
      diagnosed at the time of laparotomy. It is usually of unknown origin, although at
      times, it may be seen secondary to a variety of conditions. Tuberculosis is an
      infrequently implicated cause of abdominal cocoon, and has only occasionally been
      reported previously in the Literature. This paper presents our experience with
      tubercular cocoon as a cause of intestinal obstruction, and discusses the
      surgical implications of the same.

PMID- 16800897
TI  - Identification of putative domain linkers by a neural network - application to a
      large sequence database.
AB  - BACKGROUND: The reliable dissection of large proteins into structural domains
      represents an important issue for structural genomics/proteomics projects. To
      provide a practical approach to this issue, we tested the ability of neural
      network to identify domain linkers from the SWISSPROT database (101602
      sequences). RESULTS: Our search detected 3009 putative domain linkers adjacent to
      or overlapping with domains, as defined by sequence similarity to either Protein
      Data Bank (PDB) or Conserved Domain Database (CDD) sequences. Among these
      putative linkers, 75% were "correctly" located within 20 residues of a domain
      terminus, and the remaining 25% were found in the middle of a domain, and
      probably represented failed predictions. Moreover, our neural network predicted
      5124 putative domain linkers in structurally un-annotated regions without
      sequence similarity to PDB or CDD sequences, which suggest to the possible
      existence of novel structural domains. As a comparison, we performed the same
      analysis by identifying low-complexity regions (LCR), which are known to encode
      unstructured polypeptide segments, and observed that the fraction of LCRs that
      correlate with domain termini is similar to that of domain linkers. However,
      domain linkers and LCRs appeared to identify different types of domain boundary
      regions, as only 32% of the putative domain linkers overlapped with LCRs.
      CONCLUSION: Overall, our study indicates that the two methods detect independent
      and complementary regions, and that the combination of these methods can
      substantially improve the sensitivity of the domain boundary prediction. This
      finding should enable the identification of novel structural domains, yielding
      new targets for large scale protein analyses.

PMID- 16800899
TI  - Recurrence in skeletal muscle from squamous cell carcinoma of the uterine cervix:
      a case report and review of the literature.
AB  - BACKGROUND: The occurrence of skeletal muscle metastases is a very rare event.
      Only two cases of late skeletal muscle recurrence from cervical cancer have been
      documented until now. CASE PRESENTATION: A 38-year old patient, submitted to
      radical hysterectomy and pelvic lymphadenectomy for a squamous FIGO stage IB1
      cervical carcinoma, presented after 76 months with a palpable, and painless
      swelling on the left hemithorax. MRI showed a nodule located in the context of
      the intercostal muscles. Pathology revealed the presence of metastasis of
      squamous cell carcinoma of similar morphology as the primary. On the basis of FDG
      PET findings, which excluded other sites of disease, surgical excision of the
      lesion was performed. The patient was triaged to chemotherapy plus external
      radiotherapy. CONCLUSION: A case of skeletal muscle recurrence from cervical
      cancer after a very long interval from primary diagnosis is reported. Muscular
      pain or weakness, or just a palpable mass in a patient with a history of cancer
      has always to raise the suspicion of muscle metastasis.

PMID- 16800900
TI  - Integration of chemotherapy into current treatment strategies for brain
      metastases from solid tumors.
AB  - Patients with brain metastases represent a heterogeneous group where selection of
      the most appropriate treatment depends on many patient- and disease-related
      factors. Eventually, a considerable proportion of patients are treated with
      palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy
      in combination with chemotherapy has recently gained increasing attention and is
      hoped to augment the palliative effect of whole-brain radiotherapy alone and to
      extend survival in certain subsets of patients with controlled extracranial
      disease and good performance status. The randomized trials of whole-brain
      radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this
      concept deserves further study, although they failed to improve survival.
      However, survival might not be the most relevant endpoint in a condition, where
      most patients die from extracranial progression. Sometimes, the question arises
      whether patients with newly detected brain metastases and the indication for
      systemic treatment of extracranial disease can undergo standard systemic
      chemotherapy with the option of deferred rather than immediate radiotherapy to
      the brain. The literature contains numerous small reports on this issue, mainly
      in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very
      few sufficiently powered randomized trials. With chemotherapy alone, response
      rates were mostly in the order of 20-40%. The choice of chemotherapy regimen is
      often complicated by previous systemic treatment and takes into account the
      activity of the drugs in extracranial metastatic disease. Because the blood-brain
      barrier is partially disrupted in most macroscopic metastases, systemically
      administered agents can gain access to such tumor sites. Our systematic
      literature review suggests that both chemotherapy and radiochemotherapy for newly
      diagnosed brain metastases need further critical evaluation before standard
      clinical implementation. A potential chemotherapy indication might exist as
      palliative option for patients who have progressive disease after radiotherapy.

PMID- 16800901
TI  - Problems with forehead reflectance pulse oximetry.

PMID- 16800902
TI  - Of time and temperature, plastic and glass: specimen handling in the blood-gas
      laboratory.

PMID- 16800903
TI  - Interpretation of spirometry: we can do better than the GOLD standard.

PMID- 16800904
TI  - On the power and risks of the percent of predicted.

PMID- 16800905
TI  - Comparison of a new forehead reflectance pulse oximeter sensor with a
      conventional digit sensor in pediatric patients.
AB  - BACKGROUND: During conditions of poor perfusion, the accuracy of conventional
      extremity-based pulse oximeters may be limited. Limited evidence suggests that
      forehead perfusion may be better preserved during such periods, but pediatric
      experience with newer forehead reflectance sensors is limited. We prospectively
      compared the accuracy of a forehead reflectance sensor, the Max-Fast, with a new
      generation digit sensor in pediatric patients. METHODS: Pediatric patients > 10
      kg and who had arterial catheters were eligible for enrollment. Blood oxygen
      saturation was simultaneously measured with forehead and digit sensors, and
      compared to corresponding CO-oximetry-measured arterial oxygen saturation values
      (S(aO2)) taken at the same times. We used Bland-Altman analysis to calculate the
      bias and precision of the forehead sensor and the digit sensor relative to the
      S(aO2) values. RESULTS: We obtained 116 sample sets from 28 patients. The S(aO2)
      values ranged from 84.1% to 99.2%. The bias and precision of the forehead-to
      S(aO2) difference were 0.6% and 2.7%, respectively, versus 1.4% and 2.6%,
      respectively, for the digit-to-S(aO2) difference (p < 0.05). Bias and precision
      were 0.7% and 2.6% versus 1.7% and 2.3% for the forehead and digit sensors,
      respectively, (p < 0.05) in patients who received vasoactive medications,
      compared with 0.5% and 2.8% versus 1.1% and 2.8% (p = not significant),
      respectively, in patients who did not receive vasoactive medications.
      CONCLUSIONS: The Max-Fast sensor estimated S(aO2) as accurately as did a new
      generation digit sensor in well-perfused pediatric patients.

PMID- 16800906
TI  - Effects of syringe material, sample storage time, and temperature on blood gases
      and oxygen saturation in arterialized human blood samples.
AB  - BACKGROUND: The practice of on-ice storage of arterial-blood samples in plastic
      syringes for delayed analysis continues, and the effects of storage time and
      temperature on the measurement of blood-oxygen-saturation values (S(aO2)) have
      not been adequately described. OBJECTIVE: To determine the effects of syringe
      material, storage time, and storage temperature on normal arterialized blood gas
      and S(aO2) values. METHODS: We used a temperature-controlled extracorporeal
      circuit to "arterialize" 500 mL of fresh, whole human blood at 37 degrees C, and
      we used certified calibration gases of 12% O2 and 5% CO2 to produce normal blood
      gas values. From that arterialized blood we took 90 samples and randomly assigned
      them to 6 groups, until there were 15 samples in each group. The groups were (1)
      plastic syringe, analyzed immediately, (2) plastic syringe, stored 30 min at 0-4
      degrees C, (3) plastic syringe, stored 30 min at 22 degrees C, (4) glass syringe,
      analyzed immediately, (5) glass syringe, stored 30 min at 0-4 degrees C, and (6)
      glass syringe, stored 30 min at 22 degrees C. RESULTS: Compared to the samples
      that were analyzed immediately, the P(O2) of the samples stored in plastic
      syringes for 30 min at 22 degrees C and at 0-4 degrees C was significantly
      higher, with a clinically important magnitude of 11.9-13.7 mm Hg. The P(CO2) of
      blood stored in glass for 30 min at 0-4 degrees C was significantly lower,
      although the magnitude of the difference (1.5 mm Hg) was not clinically
      important. There were no statistically significant differences in pH or oxygen
      saturation among the 6 groups. CONCLUSION: For accurate arterial-blood-gas
      results, samples drawn in plastic syringes should be analyzed immediately. If the
      analysis is going to be delayed, the samples should be drawn and stored in glass.

PMID- 16800907
TI  - Comparison of fixed percentage method and lower confidence limits for defining
      limits of normality for interpretation of spirometry.
AB  - BACKGROUND: The use of the lower 90% confidence limit of the lower limit of
      normal (LLN(CI)), rather than a fixed percentage of the predicted value (LLN(%)),
      appears to be statistically more appropriate for interpretation of spirometry
      results. There has been no comparative assessment of these 2 definitions of the
      LLN in routine clinical practice. METHODS: We studied results of spirometry
      interpretations made with these 2 approaches, and assessed various factors that
      influence discordant classification of spirometry results. Spirometry records
      from 18,112 consecutive adult patients referred for spirometry were interpreted
      as normal, obstructive, or restrictive, based on both LLN(CI) and LLN(%).
      Discordant results were analyzed using multiple logistic regression techniques to
      identify variables that significantly affected discordant classification of
      results. RESULTS: Overall, 11.7% of the results were discordant between the 2
      methods. Agreement between the 2 methods, calculated using the kappa estimate,
      was poorer with spirometry values from women and from patients at the extremes of
      height and age. Age, sex, and height independently influenced discordant
      classification. Limits of agreement between LLN(CI) and LLN(%) were wide for all
      the spirometric variables studied--more so in women and in shorter and older
      patients. CONCLUSIONS: LLN(CI) and LLN(%) yielded different interpretations of
      spirometry data in several instances, and the 2 methods cannot be used
      interchangeably. When interpreting spirometry data in routine clinical practice,
      LLN(CI) should be preferred over LLN(%).

PMID- 16800908
TI  - Hospital discharge of respiratory-technology-dependent children: role of a
      dedicated respiratory care discharge coordinator.
AB  - BACKGROUND: Preparation of respiratory-technology-dependent children for hospital
      discharge presents many challenges. Adequate training and education of parental
      caregivers, discharge planning, and coordination with the durable-medical
      equipment and home-nursing companies must be completed. A process using multiple
      respiratory therapists (RTs) to achieve this may not be efficient. METHODS: We
      evaluated our model, in which a dedicated RT discharge coordinator provides
      education and coordinates discharge planning of respiratory-technology-dependent
      pediatric patients. This system provides a single contact for caregivers and
      outside agencies, a single respiratory-care educator for the caregivers, and a
      clinical pathway that involves the entire multidisciplinary team. Patient length
      of stay and customer satisfaction were evaluated before and after implementation
      of the discharge-coordinator program. RESULTS: Our dedicated-RT-discharge
      coordinator model was associated with rapid initiation of frequent family
      training sessions. Durable-medical-equipment-company personnel reported that they
      had increased satisfaction with the quality of training of the family caregivers.
      The members of the hospital multidisciplinary team had increased satisfaction
      with the discharge process. Patient length of stay nonsignificantly decreased
      after the implementation of the discharge-coordinator program. CONCLUSIONS: There
      are several advantages to using a dedicated RT-discharge-coordinator system for
      home-discharge preparation of respiratory-technology-dependent children.

PMID- 16800909
TI  - Immediate effects of thixotropy conditioning of inspiratory muscles on chest-wall
      volume in chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Thixotropy is a passive property of the skeletal muscle that
      depends on the muscle's immediate history of contraction and length change.
      Inspiratory-muscle thixotropy affects the end-expiratory position of the rib cage
      in normal subjects. OBJECTIVE: To determine whether a reduction in end-expiratory
      chest-wall volume occurs after thixotropy conditioning of inspiratory muscles in
      patients with chronic obstructive pulmonary disease. METHODS: Ten male subjects
      with chronic obstructive pulmonary disease (mean +/- SD forced expiratory volume
      in the first second 70+/-20% of predicted) showed an increased ratio of residual
      volume to total lung capacity (49 +/- 4.7%). The subjects conducted inspiratory
      muscle thixotropy conditioning maneuvers at 3 different chest-wall volumes (end
      expiratory volume of baseline breathing, residual volume plus 40% of expiratory
      reserve volume, and residual volume) and with 3 levels of inspiratory effort (0%,
      30%, and 100% of maximal inspiratory mouth pressure at each volume), with airway
      closure, in the sitting position. Using respiratory induction plethysmography, we
      measured the effect of effort-intensity and volume at the time of the
      conditioning maneuver on the end-expiratory chest-wall volume of the 5
      respiratory cycles immediately following the conditioning maneuver. RESULTS:
      There was a reduction in end-expiratory chest-wall volume after the conditioning
      maneuver, except when conditioning was performed at end-expiratory baseline with
      0% effort. The reduction increased as effort intensity increased (p = 0.011) and
      as volume decreased (p < 0.001), and the reduction was attained by rib-cage
      movement rather than abdominal movement. CONCLUSIONS: Thixotropy conditioning of
      inspiratory muscles, at a reduced chest-wall volume, decreased end-expiratory
      chest-wall volume in the 5 subsequent breaths in patients with chronic
      obstructive pulmonary disease.

PMID- 16800910
TI  - Use of a noninvasive pulse CO-oximeter to measure blood carboxyhemoglobin levels
      in bingo players.
AB  - BACKGROUND: Though smokers are known to have elevated blood carboxyhemoglobin
      (COHb), due to inhalation of carbon monoxide (CO) in cigarette smoke, limited
      data exist regarding COHb levels in nonsmokers exposed to secondhand smoke.
      METHODS: COHb was measured using a new noninvasive pulse CO-oximeter (Rad-57,
      Masimo, Irvine, California) in 38 subjects entering a bingo hall where smoking
      was allowed, then again as they exited 3 hours later. RESULTS: The mean +/- SD
      baseline COHb for the entire group was 3.3 +/- 1.8%, for the 23 nonsmokers it was
      2.2 +/- 0.7%, and for the 15 smokers it was 4.9 +/- 1.9%. The nonsmokers' mean
      COHb was unchanged, at 2.2 +/- 0.8%, whereas the smokers' mean COHb fell to 3.2
      +/- 1.9%. CONCLUSIONS: The nonsmokers were not significantly exposed to CO from
      secondhand smoke in the setting we tested. The smokers probably consumed fewer
      cigarettes while playing bingo than they did prior to arrival. The Rad-57 pulse
      CO-oximeter is easy to use in the ambulatory setting.

PMID- 16800911
TI  - Qualitative studies to explore barriers to spirometry use: a breath of fresh air?

PMID- 16800912
TI  - [New principles in tumor antigens and their significance in future
      immunotherapies for lymphomas and other malignancies--editorial].
AB  - The molecular characterization of self-antigens expressed by human malignancies
      that are capable of elicitation of anti-tumor immune responses in patients has
      been an active field in hematology, oncology, and tumor immunology. More than
      2000 tumor antigens have been identified. These significant progresses have led
      to the renaissance of tumor immunology and studies on novel anti-tumor
      immunotherapies in lymphomas, other hematologic malignancies and tumors. However,
      despite of the progress in the identification of these self-tumor antigens,
      current antigen-specific immunotherapies for tumors are far less satisfactory
      than that expected, which reflects the urgent need to improve our understanding
      on the basic principles underlying the selection of these self-tumor antigens. In
      order to develop more effective antigen-specific anti-tumor immunotherapies and
      to monitor the responses to these immunotherapies in patients with lymphomas and
      other malignancies, many additional questions need to be addressed. In this brief
      review, the progress in the identification of tumor antigens in lymphomas and
      other malignancies was outlined and the new principles of self-tumor antigens and
      their significance for future immunotherapies to these malignancies were
      summarized.

PMID- 16800913
TI  - [Application of CD123 in detection of minimal residual disease in acute
      promyelocytic leukemia].
AB  - The study was aimed to investigate the role and significance of CD123 with other
      immunological markers in detecting minimal residual disease (MRD) of APL
      patients. The immunophenotypes of 186 newly diagnosed APL patients and the
      percentages of cells identical with APL cell immunophenotypes in 20 normal bone
      marrow samples were analyzed using four-color flow cytometry. MRD in 172
      specimens were monitored by mainly using CD34/CD117/CD123/HLA-DR four-color
      antibody panels, meanwhile 18 specimens were analyzed with the second antibody
      combination: CD9/CD117/CD34/CD33, simultaneously and the results were compared
      with real-time PCR. One hundred and sixteen of 172 bone marrow (BM) or peripheral
      blood (PB) specimens were from follow-up 19 newly diagnosed APL patients and the
      rest 56 samples were from 47 patients treated 3 to 24 months later. Among them,
      117 samples and 55 samples were collected after achieving morphologic complete
      remission (mCR) and before achieving mCR respectively. The results of
      immunophenotyping demonstrated that except CD9, CD33 and CD117 were high
      expressed and CD34 and HLA-DR were rarely expressed, the CD123 was expressed in
      30/30 (100%) APL patients. The percentages of CD117(+)CD34(-)CD123(+)HLA-DR(-)
      and CD117(+)CD34(-)CD9(+)CD33(+) cells in nucleated cells were 0.066% +/- 0.012%
      and 0.089% +/- 0.066% in 20 normal bone marrow samples. The median time of
      achieving morphology complete remission in 19 APL patients was 4 weeks (3 - 6
      weeks). The median time of FCM and PCR results turned to be negative in 13 APL
      patients was 7.5 weeks (5 - 11) and the median time of PCR results turned to be
      negative in 11 APL patients was 8 weeks (5 - 12). 41/117 (35.04%) samples were
      MRD positive by FCM after achieving mCR. The ratio of CD117(+)CD34(-)CD123(+)HLA
      DR(-) cells was < 5% in 33 specimens, but > 5% in another 8 specimens, their
      median percentages of CD117(+)CD34(-)CD123(+)HLA-DR(-) cells were 0.48% (range
      0.02% - 4.70%) and 9.02% (range 5.26% - 18.14%) respectively. The median relative
      percentages of CD123(+)HLA-DR(-) cells in CD117(+)CD34(-) population were 63.59%
      (range 15.11% - 98.36%) and 86.77% (range 63.29% - 92.62%) respectively. In FCM
      MRD positive samples, 95.9% (93/97) were PCR positive, the false positive rate of
      FCM and the false negative rate of PCR were 4.1% (4/97) and 8.75% (7/93)
      respectively. In FCM negative samples, 92% (69/75) were PCR negative and 8%
      (6/75) were PCR positive. The percentages of CD117(+)CD34(-)CD123(+)HLA-DR(-)
      cells in 116 consecutive specimens and 117 specimens of mCR were related to
      PML/RARalpha quantified by real-time PCR (r = 0.824, P < 0.001 and r = 0.754, P <
      0.001 respectively). It is concluded that the detection of APL patients by means
      of two sets of antibody panels is simple and suitable, which is complementary to
      PCR in monitoring MRD of APL patients.

PMID- 16800914
TI  - [Expressions of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 in chronic
      myeloid leukemia cells].
AB  - This study was aimed to explore the expression of MIP-1alpha, MCP-1 and their
      receptors CCR-1, CCR-2 in bcr/abl fusion gene positive CML cells, and to study
      the effects of P210(bcr/abl) fusion protein tyrosine kinase on expression of MIP
      1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNAs in chronic myeloid leukemia
      cells. The expression levels of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR
      2 mRNA were detected by semi-quantitative RT-PCR in bcr/abl negative cells,
      bcr/abl positive cells, and P210(bcr/abl)-Rb-C-Box positive cells. The results
      showed that MIP-1alpha and CCR-1 mRNAs were expressed in bcr/abl negative cells,
      but not in positive cells. Both MCP-1 and CCR-2 mRNA cannot be detected in both
      bcr/abl positive and negative cells. After inhibiting P210(bcr/abl) tyrosine
      kinase activity by Rb-C-Box, expressions of MIP-1alpha and CCR-1 mRNAs were
      restored to normal (similar to P210(bcr/abl) negative cells). It is concluded
      that P210(bcr/abl) fusion protein inhibits the expression of MIP-1alpha and CCR-1
      in chronic myeloid leukemia cells, but does not inhibit MCP-1 and CCR-2 mRNA
      expressions in these leukemia cells.

PMID- 16800915
TI  - [Long-term survival analysis in 170 cases of acute promyelocytic leukemia].
AB  - This study was aimed to investigate various factors influencing long-term
      survival in patients with acute promyelocytic leukemia. A single institutional
      retrospective study with long-term follow-up was performed to better define the
      prognostic factors and a rationale for the use of ATRA, chemotherapy, and
      As(2)O(3) in the treatment of newly diagnosed APL patients. Newly diagnosed
      patients with APL entering complete remission (CR) were followed up for 6 to 185
      months (n = 170) from January 1990 to December 2004. Univariate and multivariate
      analysis of 8 potential factors influencing survival and prognosis were carried
      out with Log-Rank and Cox regression method, including sex, age, initial WBC
      count, the level of lactic hydrogenase (LDH), first induction regimen, time from
      induction therapy to CR, post-remission therapy, negative or positive rate of PML
      RAR alpha and follow-up of reverse transcription-polymerase chain reaction (RT
      PCR). The results showed that the estimated 5-year overall survival (OS) and
      relapse-free survival (RFS) were 80.9% +/- 4.0% and 71.0% +/- 4.0% respectively.
      The 23 patients relapsed at the median time of 15 months (6 - 70) after CR.
      Univariate analysis revealed that initial WBC count, first induction regimen,
      time from induction therapy to CR, type of post-remission therapy and persistent
      negative RT-PCR in remission were important prognostic factors for long-term
      survival. Multivariate study demonstrated that only type of post-remission
      therapy was associated with RFS and OS. It is concluded that the post-remission
      treatment combining ATRA, As(2)O(3) and chemotherapy would significantly improve
      the long-term survival of APL patients entering CR(1).

PMID- 16800916
TI  - [Expression of midkine in patients with acute myeloid leukemia and its
      significance].
AB  - The study was aimed to investigate the expression of midkine (MK) in bone marrow
      mononuclear cells (BM MNC) from 65 acute myeloid leukemia patients and 15 normal
      controls. The method of RT-PCR was used to examine the expression of MK mRNA in
      BM MNC. Parts of samples were incubated for 24 hours and the gene expression of
      MK in the BM MNC was detected by means of Western blot. The results showed that
      the expression of MK of BM MNCs in 50 newly diagnosed AML patients (0.331 +/-
      0.436) and 15 AML patients in relapse (0.374 +/- 0.463) were markedly higher than
      that in 15 CR cases (0.067 +/- 0.190), and 15 normal controls (0), respectively.
      The complete remission in MK positive patients (63.16%) was significantly lower
      than that in MK negative group (93.55%). The patients with positive MK expression
      had a higher relapse rate than those with negative MK expression. The positive
      rate of MK gene expression in drug-resistant patients and drug-sensitive patients
      were 57.69% and 25.64% respectively and there was positive correlation between
      the gene expressions of MK and bcl-2 (P < 0.01) (r = 0.0556, P < 0.001). It is
      concluded that MK can be secreted by AML cells and involved in drug-resistant,
      its positive expression may be associated with the poor prognosis in newly
      diagnosed AML patients. The inhibitory effect of MK on apoptosis of leukemic
      cells is induced by upregulating bcl-2 expression.

PMID- 16800917
TI  - [Analysis of Flt-3 expression and Flt-3/ITD mutation in acute myeloid leukemia
      cells].
AB  - This study was aimed to explore the relationship between Flt-3 expression, Flt
      3/ITD mutation in acute leukemia (AL) cell line and pathogenesis of AL,
      especially AML. The Flt-3 expression and Flt-3/ITD mutation were detected by RT
      PCR and sequencing method in 82 leukemia cell lines including 20 AML, 57 ALL and
      5 CML cell lines. The results indicated that positive results of Flt-3 expression
      were obtained in 48 out of 77 AL cell line, the positive rate was 62%; 12 cell
      lines were positive in 20 AML cell lines, the positive rate was 60%; 33 cell
      lines was positive in 57 ALL cell lines, the positive rate was 58%; 3 cell lines
      were positive in 5 CML cell lines, the positive rate was 60%. There was abnormal
      gene product in 1 AMOL cell line out of 12 AML cell lines with Flt-3 positive
      expression (positive rate 8.3%). DNA sequencing of abnormal gene product showed
      two coding duplication sequence with 29 bp long. The positive rate of Flt-3
      expression in undifferentiated cell line was prominently higher than that in
      mature B cell ALL (P < 0.05). It is concluded that the Flt-3 expression is
      different in various leukemia cells. Flt-3/ITD duplication was found in one AML
      cell line. The detection of Flt-3 gene and Flt-3/ITD mutation may contribute to
      the diagnosis of ALL, especially to AML.

PMID- 16800918
TI  - [Biological characteristics of hyperleukocytic acute leukemia].
AB  - The study was to investigate the biological characteristics of hyperleucocyte
      acute leukemia (HAL) and its clinical significance. Immunophenotyping was
      performed in 48 HAL patients and 73 NHAL patients by three-color flow cytometry
      analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed
      in 74 patients. The results showed that as compared with NHAL group, HAL group
      had lower proportion of eryth-lineage in bone marrow (P < 0.05); in AML, the CD14
      expression of HAL group was apparently higher than that of NHAL group (P < 0.05);
      in ALL, HAL group had higher expression of CD8 and lower expression of CD22,
      cCD79a compared with NHAL group (P < 0.05); the two groups had no significant
      difference in expression of special lineage antigens and overlapping lineage
      antigens (P > 0.05). The CR rate of HAL group was lower than that of NHAL group.
      It is concluded that bone marrow inhibition of HAL group is more severe than that
      of NHAL group. In AML, monocytic leukemia is easier to become into HAL than other
      leukemias. In ALL, T-lineage antigens of HAL group are more easily expressed than
      those of NHAL group; the leukemia cells of HAL group are naiver than those of
      NHAL group, meanwhile the prognosis of HAL is poor.

PMID- 16800919
TI  - [Effects of acute myeloid leukemia cell supernatant on the proliferation and
      apoptosis of CD4+ and CD8+ T cell subsets].
AB  - To study the effects of supernatant derived from acute myeloid leukemia (AML)
      cell lines on proliferation and apoptosis of CD4(+) and CD8(+) T cell subsets and
      to investigate the mechanism by which AML escapes from immune recognition,
      lymphocytes were labeled with CFSE and were stimulated with anti-CD3 and anti
      CD28 in presence or absence of supernatants from three AML cell lines (HL-60,
      NB4, U937). After culture, cell suspensions were labeled with 7AAD and CD4 PE (or
      CD8 PE). Cells were then detected by flow cytometry and their proliferation and
      apoptosis were analyzed. The results showed that supernatants from two of three
      cell lines (HL-60 and NB4) inhibited the proliferation of CD4(+) and CD8(+) T
      cells, and the degree of inhibition showed a dose-dependent way. Similarly, the
      apoptosis of stimulated CD4(+) T cells was inhibited, but stimulated CD8(+) T
      cells remained unaffected by supernatant from HL-60 and NB4. In contrary, the
      apoptosis of proliferative CD8(+) T cells were increased significantly by HL-60
      and NB4 supernatant. It is concluded that soluble factors derived from AML cell
      lines inhibit the proliferation of CD4(+) and CD8(+) T cells and induce the
      apoptosis of proliferative CD8(+) T cells, that may be one of the mechanisms by
      which the immunity was suppressed.

PMID- 16800920
TI  - [Expression and role of beta-catenin in acute leukemia bone marrow cells].
AB  - The aim of this study was to explore the expression of beta-catenin in acute
      leukemia bone marrow cells and its role in the development of acute leukemia. The
      expression of beta-catenin of bone marrow cells was detected by
      immunocytochemistry and flow cytometry in 20 cases of newly diagnosed acute
      leukemia. Meanwhile the expression of the proliferating index Ki-67 was detected
      by immunocytochemistry. The results showed that the expression of beta-catenin
      and Ki-67 in acute leukemia bone marrow cells was significantly higher than those
      in control group (P < 0.05). The migration of beta-catenin from cytoplasm to
      nuclear was observed in acute leukemia bone marrow cells. There was a positive
      correlation between the expressions of beta-catenin and Ki-67 in all the cases
      and the Pearson correlation coefficient was 0.845. In conclusion, the expression
      of beta-catenin was significantly high in acute leukemia bone marrow cells and
      showed a positive correlation with the cell proliferation. It suggests that beta
      catenin may be involved in the development of acute leukemia through promoting
      the excessive proliferation of cells.

PMID- 16800921
TI  - [Expressions of ki-67 and bcl-2 in 29 cases of chronic lymphocytic leukemia and
      their clinical significance].
AB  - To investigate the expressions of proliferative antigen Ki-67 and apoptosis
      antagonizing protein Bcl-2 in patients with chronic lymphocytic leukemia (CLL)
      and their clinical significance, immunohistochemistry method was used for
      detection of Ki-67 and Bcl-2 in bone marrow or peripheral blood of 29 patients
      with CLL. The results showed that the level of Ki-67 expression in advanced stage
      of CLL was higher than that in early stage of CLL and there was significant
      difference between these stages of CLL, but there was no significant difference
      between expression levels of Bcl-2 in two stages. The survival time in the group
      with Ki-67 expression < or = 8% was longer than that in the group of Ki-67 > 8%,
      and there was no significant difference of survival time between high and low
      groups in terms of Bcl-2 expression. It is concluded that detection of Ki-67
      antigen and Bcl-2 protein for CLL patients can reflect the status of
      proliferation activity and apoptosis suppression of leukemia cells in patients;
      the level of Ki-67 expression closely correlate with the Binet stage and
      prognosis of CLL.

PMID- 16800922
TI  - [Detection of the labile iron pool in leukemia cells and its significance].
AB  - To explore a rapid and easy method to detect labile iron of pool (LIP) in cells,
      HL-60 and K562 cells were cultured at a concentration 1 x 10(6)/ml in RPMI 1640
      containing 10% heat-inactivated fetal bovine serum. The iron deprivation was
      induced by adding desferrioxamine (DFO) 10 - 100 micromol/L for 0 - 48 hours. The
      intracellular LIP was measured by probe calcein-AM. Calcein fluorescence was
      monitored in 1420 multilabel counter. The results indicated that when HL-60 and
      K562 cells were incubated with different concentrations of DFO, the calcein
      fluorescence intensity was higher than that of control group at 12, 24 and 48
      hours (P < 0.05). Fluorescence value of representing LIP in DFO groups was lower
      than that in the control group. In conclusion, DFO can decrease LIP in leukemia
      cells. The approach used in this study may provide a simple and reliable method
      for detection of intracellular iron homeostasis.

PMID- 16800923
TI  - [Effect of aminopeptidase inhibitor on differentiation induction activity of all
      trans retinoic acid in human acute promyelocytic leukemia NB4 cells and its
      mechanism].
AB  - This study was purposed to investigate whether aminopeptidase inhibitor,
      bestatin, can potentiate all-trans retinoic acid (ATRA)-inducing differentiation
      in NB4 cells, and to explore its mechanism. The NB4 cells were exposed to either
      bestatin and ATRA alone or in combination, the morphological changes of NB4 cells
      were observed by optical microscopy, the CD11b expression was measured by flow
      cytometry, the function of defferentiation cells was analyzed by nitroblue
      tetrazolium (NBT) reduction assay, the mRNA expressions of c-myc and c-EBPepsilon
      in NB4 cells were detected by RT-PCR, the c-Myc protein expression was determined
      by Western blot. The results showed that treatment with bestatin alone induced no
      significant changes in morphology, NBT reduction activity and CD11b expression in
      NB4 cells. NB4 cells incubated with 10 nmol/L ATRA plus 100 microg/ml bestatin
      showed more morphologic feature of metamyelocyte and band neutrophil than ATRA
      alone treated cells. 100 microg/ml bestatin enhanced the NBT reduction activity
      in NB4 cells induced by various concentrations of ATRA (10, 20, 40 nmol/L). The
      effects of various concentrations of ATRA in combination with 100 microg/ml
      bestatin were statistically different from the effect of ATRA alone (P < 0.01).
      From 48 to 96 hours, 100 microg/ml bestatin time-dependently increased NBT
      reduction in NB4 cells induced by 10 nmol/L ATRA (P < 0.01). 10 nmol/L ATRA plus
      100 microg/ml bestatin for 72 hours prominently elevated CD11b expression in NB4
      cells as compared with ATRA alone treated NB4 cells (P < 0.01). There was a
      substantial decrease in c-myc mRNA levels when 100 microg/ml bestatin was added
      to 10 nmol/L ATRA (P < 0.05). Various concentrations (50, 75, 100 microg/ml) of
      bestatin combined with 10 nmol/L ATRA down-regulated the expression of c-Myc
      protein, which was negatively correlated with the NBT reduction activity of NB4
      cells induced by 10 nmol/L ATRA alone or plus bestatin at various concentrations
      (r = -0.940, P = 0.017). However, 100 microg/ml bestatin plus 10 nmol/L ATRA
      could not induce any significant changes in the levels of c-EBPepsilon mRNA as
      compared with ATRA alone treated NB4 cells. It is concluded that an
      aminopeptidase inhibitor bestatin can potentiate ATRA-inducing differentiation of
      NB4 cells, possibly by down-regulating c-myc expression in synergy with ATRA.

PMID- 16800924
TI  - [Effects of recombinant human tumor necrosis factor-alpha on HL-60 cells in vitro
      and in vivo].
AB  - To study the effects of recombinant human tumor necrosis factor-alpha (rhTNF
      alpha) on HL-60 cells in vitro and in vivo, MTT and colony forming assay were
      used to examine the effects of rhTNF-alpha on proliferation of HL-60 cells; AO/EB
      (acridine orange-ethidium bromide) staining, Annexin-V flow cytometry analysis
      and TUNEL assay were used to detect apoptotic cells. The effect of rhTNF-alpha on
      xenograft growth of HL-60 cells was evaluated by tumor inhibition rate,
      histology, ultrastructure and TUNEL assay. The results showed that rhTNF-alpha
      inhibited the proliferation of HL-60 cells in a dose-dependent manner. Staining
      of cells with AO/EB revealed that rhTNF-alpha induced nuclear chromatin
      condensation and fragmentation. Positive Annexin V-FITC on cell membrane showed
      that rhTNF-alpha induced apoptosis of HL-60 cells in a dose-dependent manner.
      TUNEL assay showed that the apoptotic percentage of HL-60 cells reached 37.5%
      when incubated with 3200 U/ml rhTNF-alpha for 48 hours. In vivo rhTNF-alpha
      inhibited xenograft growth of HL-60 cells with the highest inhibition rate of
      60.33%. Pathologically it was found that there were necrotic areas in the tumors
      of groups treated with rhTNF-alpha. There were more apoptotic cells in treatment
      groups than in that control group by transmission electron microscopy (TEM) and
      TUNEL assay. It is concluded that rhTNF-alpha is able to inhibit the
      proliferation of HL-60 cells and to induce apoptosis of HL-60 cells in vitro and
      in vivo.

PMID- 16800925
TI  - [Influence of chemotherapy on expression of TRAIL in primary acute leukemic
      cells].
AB  - In order to explore the expression of TRAIL in primary acute leukemic cells and
      the effect of chemotherapeutic drug on TRAIL expression in acute leukemic cells,
      the expression of TRAIL was assessed by flow cytometry on day 0, day 1, day 3 and
      day 5 in 16 patients with acute leukemia received chemotherapy. Meanwhile, the
      bone marrow mononuclear cells of acute leukemia patients were cultured in vitro
      with VP-16 and INFalpha-2a. Expression of TRAIL was analyszed by flow cytometry
      at 24, 48 and 72 hours after treatment. The results showed that the expression of
      TRAIL in the peripheral blood mononuclear cells was upregulated significantly
      from day 1 after chemotherapy (P < 0.05). In in vitro culture test, VP-16
      upregulated the expression of TRAIL on acute leukemia bone marrow mononuclear
      cells (P < 0.05). Compared with VP-16 alone, the combination of VP-16 with
      IFNalpha-2a showed no synergic effects on the expression of TRAIL. It is
      concluded that the expression of TRAIL increases after chemotherapy in vivo and
      after treatment with VP-16 and IFN in vitro, which suggests that the apoptosis
      induced by TRAIL may play an important role in chemotherapy of leukemia.

PMID- 16800926
TI  - [Deferoxamine induces apoptosis of HL-60 cells by activating caspase-3].
AB  - This study was purposed to observe the changes of caspase-3 activity during
      apoptosis of HL-60 cells induced by an iron chelator, DFO (deferoxamine), and to
      explore the mechanism underlying apoptosis in HL-60 cells. The HL-60 cells
      treated with DFO were examined by light microscopy, flow cytometry (FCM) and DNA
      agarose gel electrophoresis; the activity of caspase-3 was determined by cellular
      immunohistochemistry; the transcription of the apoptotic gene of bax was detected
      by hybridization in situ. The results showed that the typical morphological
      character of apoptosis cells, DNA ladder and FCM assay confirmed that DFO could
      induce the apoptosis in HL-60 cells. The apoptotic rate increased in dose-and
      time-dependent manner. When cells had been cultivated with 100 micromol DFO for
      12 hours, a few caspase-3 positive cells were found. In the process of time, the
      rate of caspase-3 positive cells was progressively higher than that in control (P
      < 0.05), while the level of bax transcription was also higher than that in the
      control. It is concluded the activation of caspase-3 and gene bax may be involved
      in the apoptosis of HL-60 cells induced by DFO.

PMID- 16800927
TI  - [Effect of the NHE-1-specific inhibitor DMA on pHi, proliferation and apoptosis
      of HL-60/ADM cells in vitro].
AB  - The aim of this study was to evaluate the effect of dimethyl amiloride (DMA), a
      specific inhibitor of Na(+)/H(+) exchanger-1 (NHE-1), on intracellular pH value
      (pHi), proliferation and apoptosis of HL-60/ADM cells in vitro. After treatment
      with DMA at different doses, pHi of HL-60 and HL-60/ADM cell lines were
      determined by using pH-sensitive fluorescence dye BECEF-AM; the rate of growth
      inhibition of cells was detected with MTT assay; cell cycle was detected by flow
      cytometric DNA analysis; cell apoptosis was observed with terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The results
      showed that pHi in HL-60/ADM cells was higher than that in HL-60 cells. After
      treatment with DMA at different doses, pHi decreased, the rate of growth
      inhibition and the rate of apoptotic cells in HL-60/ADM cells were all higher
      than those in HL-60 cells. Meanwhile, after treatment with DMA during 100
      micromol/L to 150 micromol/L, the increase amplitude of G(0)/G(1) phase cells and
      the decrease amplitude of S + G(2)/M cells in HL-60/ADM cells were higher than
      those in HL-60 cells. It is concluded that by causing intracellular
      acidification, the NHE-1-specific inhibitor DMA inhibits proliferation of HL
      60/ADM cells and induces apoptosis of HL-60/ADM cells, and the degree of this
      growth inhibition of HL-60/ADM cells is higher than that of HL-60 cells.

PMID- 16800929
TI  - [ERK pathway change in the differentiation of human MDS cell lines SKM-1 induced
      by sodium butyrate].
AB  - The study was purposed to investigate the role of extracellular signal-regulated
      kinase (ERK) pathway in the differentiation of human MDS cell lines SKM-1 induced
      by sodium butyrate (NaB), and to elucidate the molecular mechanism of
      differentiation in SKM-1 cells induced by NaB. The expression levels of total ERK
      and phosphorylated-ERK were determined by Western blot. The effect of NaB in
      combination with the ERK inhibitor PD98059 on the proliferation/differentiation
      of SKM-1 cells was studied, and then the expression levels of the P21 and HDAC
      protein were detected by Western blot. The results showed that the expression
      level of phosphorylated ERK was down-regulated by the 1 mmol/L NaB, and the level
      of total ERK had not changed. NaB or combination of the MEK inhibitor PD98059
      with NaB could increase the differentiation of the SKM-1 cells and up-regulated
      the levels of the P21 and HDAC protein, but the effect of combination of NaB with
      PD98059 was higher than that of NaB alone. It is concluded that the inhibition of
      ERK may be involved in sodium butyrate inducing differentiation in SKM-1 cells.

PMID- 16800928
TI  - [Difference of gene expression profiles between HL-60/VCR and HL-60 cells
      detected by human genome genechip].
AB  - This study was aimed to detect the gene expression profile changes between human
      acute leukemia cell line HL-60 and VCR-resistance HL-60, and to investigate the
      underlying mechanisms of MDR by using genechip technology. In experiments, mRNA
      were harvested using TrizoL reagent from these two cell lines, through RT-PCR,
      the biotinylated nucleotide were incorporated into the cRNA during the in vitro
      transcription reaction. The high quality RNA was hybridized to the gene
      expression array--human genome U133A developed by Affymetrix. It was scanned by
      G2500A GeneArray Scanner and the acquired image was analysed by a series of
      softwares. The results showed that 5,507 genes were differentially expressed
      between human acute leukemia cell line HL-60 and VCR-resistant HL-60. Compared
      with HL-60, 3,100 genes were up-regulated and 2,407 genes were down-regulated in
      VCR-resistant cell line. These genes were involved in different cell activities
      such as growth regulation and signal transduction. Among the genes with
      remarkable differential expression between the two cell lines, 435 were up
      regulated and 605 were down-regulated. It is concluded that many different kinds
      of genes are involved in the mechanism of MDR and there is an intricate molecular
      network that controls the sensitivity of leukemia cells to the chemotherapeutic
      agents. Genechip is an efficient tool for parallel gene expression analysis.

PMID- 16800930
TI  - WT1 gene expression lowered by IL-12 In vitro in peripheral blood mononuclear
      cells from patients with leukemia or myelodysplastic syndromes.
AB  - Previous studies demonstrated that interleukin-12 (IL-12) enhances the non-MHC
      restricted cytotoxic activity of NK cells and facilitate specific allogeneic
      human cytotoxic T lymphocyte responses against fresh leukemia cells and cell
      lines. The Wilms' tumor gene, WT1 mRNA, has been used as a marker of minimal
      residual disease (MRD) for evaluating therapeutic efficacy of patients with
      leukemia or myelodysplastic syndrome (MDS). This study was aimed to investigate
      whether in vitro IL-12 can lower WT1 gene expression in peripheral blood
      monuclear cells (PBMNC) from patients with leukemia or MDS. PBMNC from these 30
      patients and 5 healthy volunteers were cultured at 5 x 10(5) cells/ml alone with
      or without 100 units/ml of IL-12 for 3 days. WT1 mRNA was measured by competitive
      reverse transcription polymerase chain reaction (RT-PCR) since WT1 mRNA is
      considered as a marker of minimal residual disease (MRD) in leukemia and MDS. The
      results demonstrated that WT1 mRNA in PBMNC of 5 healthy volunteers was less than
      10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1
      mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in 6
      CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from
      10(5.0) to 10(4.2) copies/microg in 5 AML patients in CR, but not reduced in 5 of
      7 AML in non-CR. It is concluded that IL-12 significantly decrease the quantity
      of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12
      may be of considerable benefit in the elimination of MRD in patients with
      hematological malignancies.

PMID- 16800931
TI  - [Expression of P120ctn in non-Hodgkin's lymphoma and its significance].
AB  - To evaluate the expression of P120ctn in non-Hodgkin's lymphoma (NHL) and to
      explore its clinical significance, immunohistochemistry stain method was applied
      to comparatively investigate the protein expression of P120ctn in paraffin
      embedded lymph node tissue slices from 40 cases of NHL and 10 cases of reactive
      hyperplasia of lymph node. The results showed that P120ctn was not detected in
      reactive hyperplasia of lymph node, but was detected in 55% (22/40) cases of NHL.
      P120ctn expression increased with the tumor malignancy of NHL, there was a
      significant difference between the expression rates of P120ctn in low grade
      (16.7%, 2/12) and intermediate to high grade malignant (71.4%, 20/28) NHL (P <
      0.001). Moreover, P120ctn was also detected in vascular endothelial cells of NHL.
      It is concluded that the level of P120ctn expression is closely related to the
      malignant grade of NHL, it suggests that P120ctn possibly plays an important role
      in the malignant proliferation of lymphoma with a certain significance in
      diagnosis and therapy of lymphoma.

PMID- 16800932
TI  - [Renin angiotensin system in bone marrow of patients with aplastic anemia].
AB  - Renin-angiotensin system (RAS) has been shown to be involved in the growth,
      production, proliferation and differentiation of the bone marrow (BM)
      hematopoietic cells, while aplastic anemia (AA) is a disease in which
      proliferation ability of the BM hematopoietic cells is damaged with defective
      hematopoietic microenvironment. To investigated the pathogenesis of AA, the
      rennin activity, angiotensin I (Ang I) and angiotensin II (Ang II) concentration
      in peripheral blood and BM of 22 AA patients were detected by radioimmunoassay,
      16 nonhematological disease patients with normal blood counts and BM picture were
      used as control, and the difference between two groups was compared. The results
      showed that BM Ang II concentration in the AA patients was significantly lower
      than that in the control (P < 0.01). In nonhematological disease patients, Ang II
      concentration in BM was significantly higher than that in peripheral blood, the
      renin activities and Ang I concentrations were not significantly different in the
      two groups (P > 0.05). In conclusion, the decreased BM Ang II concentration in AA
      patients may be involved to the pathogenesis of AA.

PMID- 16800933
TI  - [Variant fusion transcript in ALL children with E2A-PBX1 fusion gene positive].
AB  - The study was aimed to investigate the expression of E2A-PBX1 fusion gene in
      children with acute lymphoblastic leukemia (ALL). The primers located at
      different sites of E2A and PBX1 gene were used to screen for the fusion gene in
      410 children with ALL, including 362 cases of B cell ALL and 48 cases of T cell
      ALL. The results showed that 17 children carried the fusion gene. The positive
      rate was 4.1%. Furthermore, all the positive cases expressed a variant type of
      fusion transcript. It resulted from different splicing of the 13th exon (159 bp)
      of E2A gene. Analyses with BLASTn indicated that the variant type of transcript
      retained the open reading frame. However, the loss of 53 amino acid residues
      which were located at the 2nd activation domain resulted in the partial deletion
      of the putative loop-helix (LH) structure as well as the complete deletion of the
      heptad leucine repeat. It is concluded that all the children with ALL positive
      for the E2A-PBX1 fusion gene express typical and variant fusion transcripts. The
      latter resulted from different splicing of the 13th exon (159 bp) of E2A gene.
      The loss of 53aa would lead to the partial deletion of the putative loop-helix
      (LH) structure as well as the complete deletion of the heptad leucine repeat.

PMID- 16800934
TI  - [Cloning of Human beta2-microglobulin gene and efficient expression in
      Escherichia coli].
AB  - Human beta(2)-microglobulin (beta(2)m) is the light chain of major
      histocompatibility complex (MHC) class I molecule. High-yield production of this
      protein is a prerequisite to the preparation of MHC class I tetramer. The present
      study was aimed to obtain recombinant human beta(2)m expressed in Escherichia
      coli (E. coli) for preparing MHC class I tetramers. For cloning of human beta(2)m
      gene, a pair of specific primers was designed based on the published sequence of
      this gene. A 300 bp specific DNA fragment corresponding to the encoding region of
      beta(2)m lack of the signal peptide sequence was obtained by RT-PCR from the
      total RNA of human leukocytes. The amplified cDNA was inserted into the IPTG
      inducible expression plasmid pET-17b by Nde I and Bam H I sites and its sequence
      was confirmed by DNA sequence analysis. The recombinant plasmid pET-beta(2)m was
      transformed to the competent cells of E. coli BL21 (DE3). The results showed that
      beta(2)m was expressed in the form of inclusion body and amounted to over 32% of
      total cell proteins after IPTG induction. After washing with triton X-100 and
      urea, the inclusion body was dissolved with 4 mol/L urea and then purified with
      Sephacryl S-200 HR, and the final purity reached above 95%. The denatured protein
      was renatured by dilution method. Western blot assay indicated that the
      monoclonal antibody against human native beta(2)m could react specifically with
      the recombinant protein. In conclusion, the human beta(2)m gene was cloned
      successfully and expressed efficiently in E. coli BL21 (DE3). This work
      establishes a convenient approach for renaturation and purification of large
      quantity of recombinant beta(2)m. This provides the basis for the preparation of
      MHC tetramers.

PMID- 16800935
TI  - [Transfection efficiency of adenoviral vector AD5/F35 to malignant hematopoietic
      cells of different origins].
AB  - This study was aimed to investigate the transfection efficiency of adenoviral
      vector AD5/F35 to hematopoietic malignant cells lines of various origins and
      AD5/F35 cytotoxicity. The hematologic malignant cell lines of various origins
      were transfected by AD5/F35-EGFP at different multiple of infection (MOI) and AD5
      EGFP was used as control; the proportion of fluorescence positive cells was
      detected by flow cytometry; the killing effect of virus on infective target cells
      was assayed by MTT and observed by fluorescence microscopy. The results showed
      that the transfection efficiency of AD5/F35 vector to cell line of myeloid origin
      was > 99% at MOI = 30, the transfective efficiency of AD5 vector was 26.4% at MOI
      = 1,000; the transfection efficiency of AD5/F35 vector and AD5 vector to cell
      line of B cell origin were 11.7% and 5.7%, respectively, at MOI = 1,000. AD5/F35
      and AD5 vectors could not effectively transfect cells of T cell origin, no
      fluorescence positive cells were detected at MOI = 1,000; no significant killing
      effect of AD5/F35 vector on infective target cells was observed at MOI = 1,000.
      It is concluded that AD5/F35 vector infection has definite selectivity to
      hematologic malignant cells of various origin, the infection ability of AD5/F35
      vector to cells of myeloid origin is stronger than that to cells of B cell
      origin, the cytotoxicity of AD5/F35 vector to infective target cells is small.
      The AD5/F35 vector is preferable to AD5 vector in respect of infection ability
      and offers good prospects of application in gene therapy for myeloid leukemia
      cells as target cells.

PMID- 16800936
TI  - [Preparation of placental-eluted gamma globulin and its immunosuppressive effect
      in vitro and in vivo].
AB  - The aim of this study was to establish a simple, convenient and efficient method
      of producing placental-eluted gamma globulin (PEGG) from human placenta, explore
      its inhibitory effect on the function of T lymphocyte in vitro and graft-versus
      host disease (GVHD) in vivo. PEGG was prepared by elution at acid pH from human
      placental tissues that were extensively washed. Its effects on T lymphocyte
      proliferation induced by PHA and mixed lymphocyte reaction (MLR) were analysed by
      BrdU ELISA, its effect on the CD25 and CD69 expression on T cells was observed by
      flow cytometry, and the interferon gamma (IFN-gamma) and interleukin-4 (IL-4)
      quantification in MLR supernatant were assayed by ELISA. A murine GVHD model was
      established, the effect of PEGG on the manifestation and pathologic change of
      GVHD and 45-day survival rate were observed. The results showed that considerable
      level of immunoglobulin could be eluted from placenta at acid PH, of which the
      main components were IgG checked by SDS-PAGE analysis. In vitro study indicated
      that PEGG significantly inhibited both the proliferative response of T cells to
      PHA and the MLR, down-regulated the expression of CD25 and CD69 on T cells
      stimulated by PHA, and decreased the secretion of IFN-gamma but increased the
      production of IL-4 in MLR supernatant. In vivo, recipient mice treated with PEGG
      had a markedly increased survival rate with less histopathological evidence of
      GVHD. It is concluded that PEGG can inhibit the proliferation and activation of T
      cells, regulate the direction of T helper cells differentiating towards Th2 type,
      and effectively prevent GVHD in a murine model. In short, PEGG may be a potent
      therapeutic agent for GVHD.

PMID- 16800937
TI  - [Expression of immune response molecules and function of fas ligand on surface of
      AML WEHI-3 cells].
AB  - The purpose of this study was to investigate the expression of Fas, Fas ligand
      (FasL) and CD80 and function of FasL on the surface of acute myelomonocytic
      leukemia cells from WEHI-3 line. The expression of Fas, FasL and CD80 on the
      surface of WEHI-3 were detected by flow cytometry, the apoptosis of YAC-1 cell
      induced by FasL on the surface of WEHI-3 were detected by (3)H-TdR incorporation.
      The results showed that the expression rate of Fas, FasL and CD80 on the surface
      of WEHI-3 cells were (6.75 +/- 2.31)% (n = 5), (63.73 +/- 5.23)% (n = 5) and
      (5.06 +/- 0.41)% (n = 5) respectively. The apoptosis rate of YAC-1 cells (target
      cells) co-cultured with WEHI-3 cells (Effector cells) at the rate of 1:3, 1:10
      and 1:30 were (26 +/- 4.5)%, (35 +/- 3.2)% and (43 +/- 2.7)% (n = 5)
      respectively. It is concluded that WEHI-3 cells have high expression of FasL and
      low expression of Fas and CD80 on their cell membrane, and can induce the
      apoptosis of Fas(+) YAC-1 cells.

PMID- 16800938
TI  - [Indoleamine 2, 3-dioxygenase activity in acute myeloid leukemia cells
      contributing to tumor immune escape].
AB  - This study was aimed to investigate the mechanism of indoleamine 2, 3-dioxygenase
      (IDO) activity in acute myeloid leukemia cells contributing to tumor immune
      escape. Myeloid leukemia cells were isolated from bone marrow of 23 patients with
      acute myeloid leukemia (AML) and IDO expression was detected by immunochemistry
      and RT-PCR methods. Then mixed lymphocyte reaction (MLR) of one way was carried
      out, leukemia cells were used as stimulating cells and T-lymphocytes were used as
      reactive cells in culture with or without 1-MT. T-lymphocyte proliferation rate
      was determined by MTT assay and IDO activity in supernatant of MLR was detected
      by high-performance liquid chromatography (HPLC). The results showed that IDO
      expression was found in 17 out of 23 cases of acute myeloid leukemia cells; IDO
      enzyme activity in leukemia cells inhibited T-lymphocyte proliferation in MLR
      cultures. It is concluded that IDO activity expressing in leukemia cells can
      suppress T-lymphocyte proliferation responses, which may be contributing to tumor
      immune escape.

PMID- 16800939
TI  - [Killing activity in DC and CIK co-culture against hepatocarcinoma cells].
AB  - This study was aimed to investigate the proliferation activities and phenotype
      changes of DC, CIK and DC-CIK, and their cytotoxicity against hepatocarcinoma
      cells in co-culture of DC with CIK. Peripheral blood mononuclear cells (PBMNC)
      were isolated from healthy adult donors. After incubation of PBMNC for 2 hours,
      DCs were induced from adherent cells by some cytokines and CIKs were generated
      from non-adherent cells. Mature DCs were harvested after incubation for 9 days,
      and then were co-cultured with CIK at ratio of 1:5 for 3 days. The cytotoxicity
      activity against SMMC-7721 hepatocellular carcinoma cell line was detected by MTT
      assay. The results showed that CIK cells were able to lyse SMMC-7721
      hepatocellular carcinoma cells at low ratios of effector to target. This effect
      was significantly enhanced by co-culture with DCs. It is concluded that CIK cells
      have high lytic activity against 7721 hepatocellular carcinoma cell line, which
      can be enhanced by co-culture with DC. DC-CIK cells are highly effective immune
      cells.

PMID- 16800940
TI  - [Anti-CD28 antibody costimulation enhances anti-CD3 antibody activating T cells
      and lowering TGF-beta expression in vitro].
AB  - In order to study how to activate T cells and their immunological
      characteristics, the anti-CD3 and anti-CD28 McAbs were used to stimulate PBMNC,
      then their related immunological changes, such as lymphocyte transformation
      function, the percentage of CD8(+)CD25(+) cells and TGF-beta expression were
      deleted by lymphocyte transformation assay, flow cytometry and RT-PCR
      respectively. The results showed that in costimulation with anti-CD28 antibody
      stimulation, the activity of anti-CD3 antibody was significantly enhanced, the
      ratio of CD8(+)CD25(+) cells of T cells was obviously increased, while TGF-beta
      expression was down-regulated. It was concluded that the anti-CD28 antibody
      costimulation could provide stimulatory signal II, which make T cells more
      active, while the expression of TGF-beta significantly down-regulated.

PMID- 16800941
TI  - [Osteoblasts differentiated from human marrow bone mesenchymal stem cells support
      hematopoietic stem/progenitor cells from umbilical cord blood].
AB  - This study was aimed to construct a two-dimensional culture system by using
      osteoblasts induced from human marrow mesenchymal stem cells (MSC) and to
      investigate its support effect on survival of hematopoietic stem/progenitor cells
      for umbilical cord blood (UCB) ex vivo. MSCs were isolated from adult human bone
      marrow and were cultured, the second generation of MSCs were induced into
      osteoblasts which were irradiated with 20 Gy gamma rays in a Cobalt 60 source and
      confluenced into a feeder layer. CD34(+) cells were selected from fresh umbilical
      cord blood samples by using Microbead Kit of MiniMACS and seeded into the two
      dimensional culture system to culture ex vivo without exogenous cytokines. By
      using colony-forming assay, high proliferative potential colony-forming cell
      assay, and long-term culture initiating cell assay, the ability of the two
      dimensional system to culture HSCs/HPCs was observed. The results showed that the
      osteoblasts induced from bone marrow MSC in constructed two-dimensional culture
      system displayed more significant support effect on survival of hematopoietic
      stem/progenitor cells from umbilical cord blood (UCB) ex vivo, compared with
      other culture systems, especially on long term HSCs survival ex vivo. It is
      concluded that the two-dimensional culture system constituted by osteoblasts
      induced from human MSCs has certain ability of supporting maintenance and
      multipotency of HSCs/HPCs from umbilical cord blood in vitro, especially
      sustaining survival of HSC in long-term culture. It has also been proved that
      osteoblasts play a crucial role in regulation of HSC growth.

PMID- 16800942
TI  - [A modified method to isolate and identify the adult mesenchymal stem cells from
      human bone marrow].
AB  - The study was aimed to establish a protocol of isolating and culturing adult
      mesenchymal stem cells (MSC) from human bone marrow aspirate and identify them by
      surface antigen analysis and committed differentiation in order to provide an
      experimental foundation for achieving a therapeutic benefit in applying MSC in
      hematopoietic stem cell transplantation. MSCs were obtained from fresh human bone
      marrow aspirate by gradient centrifugation with Percoll (1.073 g/ml) and
      anchoring culture in L-DMEM with 10% fetal bovine serum by a full medium exchange
      every 3 days. The MSC surface antigens, including CD34, CD45, CD73, CD105, CD166,
      were analyzed on FACScan flow cytometer. Under culture in conditioned medium for
      osteogenesis (the hormone cocktail containing 0.1 micromol/L dexamethasone, 10
      mmol/L glycerol-2-phosphate and 50 micromol/L ascorbic acid) and adipogenesis
      (the cocktail containing 1 micromol/L dexamethasone, 5 mg/L insulin, 0.5 mmol/L 1
      methyl-3-isobutylxanthine and 60 micromol/L indomethacin), MSCs committedly
      differentiated into osteoblasts and adipocytes. The differentiated mesenchymal
      stem cells were identified by morphological observation and immunohistochemical
      staining. The results showed that by gradient centrifugation and adhesion
      culture, MSCs could be isolated and culture-expanded from human bone marrow
      aspirate. These cells were uniformly negative for CD34, CD45 and positive for
      CD73, CD105 and CD166. The osteogenic differentiated cells were positive for
      alkaline phosphatase (ALP) and the adipogenic differentiated cells displayed
      accumulation of lipid vacuoles, as detected by oil red O. It is concluded that
      MSC can be isolated and expand-cultured from adult human bone marrow aspirate and
      committedly differentiate into osteoblasts and adipocytes. MSC primary
      identification can be accomplished by flow cytometry and induced differentiation.
      The set of methods in current experiment shows somewhat practical value for basic
      research and clinical application.

PMID- 16800943
TI  - [Platelet-derived microparticles stimulate proliferation of granulocyte
      macrophage progenitor cells from umbilical cord blood].
AB  - This study was aimed to investigate the effect of platelet-derived microparticles
      (PMP) on stimulating the proliferation of granulocyte-macrophage progenitors (CFU
      GM) from umbilical cord blood. Different concentrations of thrombin were adopted
      to activate the platelets for releasing PMP. Flow cytometry was adopted to
      evaluate the efficiencies of different concentrations of thrombin to produce PMP.
      Umbilical cord blood mononuclear cells (MNC) were obtained from healthy donors
      and the MNC were isolated by Ficoll density gradient centrifugation. MNC were
      cultured in 2.7% methylcellulose containing different concentration of PMP and
      colonies were counted under an inverted microscope after 7 days. The result
      showed that the release rate of PMP activated by 2.0, 1.5, 1.0 and 0.5 U/ml
      thrombin were 28.7%, 47.7%, 50.1% and 43.9% respectively. The PMP enhanced colony
      formation in dose-dependent manner. The number of colonies per 2 x 10(5) MNCs in
      groups of PMP at different concentrations (10, 50 and 100 microg/ml) were 119.8
      +/- 32.2,142.8 +/- 45.2 and 180.8 +/- 85.1 respectively. The number of colonies
      in the groups of PMP at 100 microg/ml and 50 microg/ml were statistically
      significant when compared with control group (103.0 +/- 24.8) (P < 0.05). The
      number of colonies per 2 x 10(5) MNC in the group of PMP (10 microg/ml) was 119.8
      +/- 32.2 which was higher than that in control group, but there was no
      statistical significance between two groups. It is concluded that platelet
      activated with 1.0 U/ml thrombin can get the best release efficiency of PMP and
      PMP can enhance the proliferation of granulocyte-macrophage progenitor cells of
      umbilical cord blood.

PMID- 16800944
TI  - [Overexpression of hypoxia inducible factor-1alpha (HIF-1alpha) promotes the
      differentiation of endothelial progenitor cell ex vivo].
AB  - To investigate the influence of HIF-1alpha overexpression on the differentiation
      of endothelial progenitor cells (EPCs) ex vivo, EPCs were isolated from human
      peripheral blood by density gradient centrifugation, overexpressed HIF-1alpha was
      transfected to EPCs by electroporation; HIF1alpha, HIF1beta, vascular endothelial
      growth factor (VEGF) mRNA level were measured with RT-PCR; HIF-1alpha protein was
      detected with immunohistochemistry in a time course. CD31(+) cells were measured
      with flow cytometry. Cell morphology was observed after transfection. The results
      showed that the transfection efficiency of HIF-1alpha to EPCs was about 20%. HIF
      1alpha and its controlled target gene VEGF were markedly induced by HIF-1alpha
      vector (P < 0.05). HIF1beta had its same level as it before interference (P >
      0.05). HIF-1alpha protein was induced by HIF-1alpha transfection after 12 hours
      but was undetectable at 24 hours. After 7 - 14 days cultured in 21% oxygen
      pressure, fluorescence-trace experiments revealed that CD31 + EPCs/EC could be
      generated more efficiently from overexpressed HIF-1alpha than that from pEGFP
      transfected group (P > 0.05). EPC morphology was observed by light microscopy.
      HIF-1alpha-transfected cells under normoxia sprouted more rapidly from the EPC
      colonies than the untransfected cells or cells transfected with an GFP vector,
      which essentially maintained the original colony formation. HIF-1alpha
      transfected cells took on an array-like arrangement rather than random dispersal,
      suggesting that they were in an advanced state of differentiation. It is
      concluded that the utility of overexpression of HIF-1alpha can induce target
      genes which have influence on cell differentiation. HIF-1alpha transfection was
      found to give a prospected way to do the insight research on ischemic treatment
      in vivo.

PMID- 16800945
TI  - [Kinetic study of various cytokine mRNA expressions in rhesus treated with
      haploidentical peripheral blood stem cell transplantation].
AB  - This study was aimed to analyze the mRNA expression of cytokines (TGF-beta, IL-2,
      IL-6, IL-10, IFN-gamma, TNF-alpha, FAS-L) in five rhesus treated with
      haploidentical peripheral blood stem cell transplantation after nonmyeloablative
      preparative regimens and to explore the role of these cytokines in the
      development and pathology of acute graft-versus-host-disease (aGVHD). Five rhesus
      monkeys received nonmyeloablative haploidentical peripheral blood stem cells
      transplantation. Semi-quantitative reversed transcription polymerase chain
      reaction (RT-PCR) was used to analyze the kinetics of cytokine mRNA expression in
      the transplantation and aGVHD. The results showed that five rhesus monkeys
      acquired hematopoietic reconstitution successfully. The graft was rejected in one
      monkey which survived without disease, the other four achieved mixed chimerism
      and full donor chimerism. Chimerism of low centigrade in one monkey achieved high
      centigrade at 35 days after donor stem cell infusion. Intestinal aGVHD grade III
      developed in one monkey. Cytokines of Th1 and Th2 changed after transplantation.
      In period of aGVHD, expression of TGF-beta decreased but all others increased in
      various levels. When donor chimerism decreased, the cytokines decreased
      accordingly. It is concluded that the decrease of TGF-beta mRNA may be an
      indicator to predict aGVHD, and can be used as a differential diagnostic
      indicator for intestinal GVHD.

PMID- 16800946
TI  - [Monitoring of bcr/abl fusion gene by interphase-dual-color and dual-fusion
      fluorescence in situ hybridization in CML after allo-HSCT].
AB  - This study was aimed to investigate the sensitivity and clinical application
      value of interphase-dual-color and dual-fusion fluorescence in situ hybridization
      (DD-FISH). The minimal residual disease (MRD) in 19 patients with chronic
      myelogenous leukemia (CML) after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) was detected by DD-FISH, and the detected results
      were compared with those of conventional cytogenetics (CC) and reverse
      transcription-polymerase chain reaction (RT-PCR). The samples were collected from
      bone marrow or peripheral blood or smears of bone marrow. The results indicated
      that 14 out of 19 patients achieved and maintained continuous complete molecular
      remission after transplantation. In these patients, CC assay displayed normal
      donor karyotype, result of RT-PCR was negative, complete donor chimerism was
      detected after 2 months of transplantation, result of DD-FISH was negative,
      average time of the follow-up survey was 11.25 months, MRD did not increase.
      Results of CC and RT-PCR in 1 patient showed negative, while FISH of sex
      chromosome showed mixed chimerism, result of DD-FISH was positive, MRD did not
      increase, no therapy was given for this patient, clinical state of patient was
      stable. Three patients with hematological relapse demonstrated obvious increase
      of MRD detected by DD-FISH and sex FISH, result of RT-PCR was found positive in
      them, but the abnormal result of CC was observed only in 1 patient. After donor
      lymphocyte infusion and imatinib mesylate treatment, these 3 patients achieved
      cytogenetic remission again, results of DD-FISH, CC and PCR were negative in
      them. DD-FISH, CC and PCR in bone marrow and peripheral blood from one patient
      with extramedullary relapse revealed negative results, and the complete chimerism
      was found in this patient. It is concluded that interphase-dual-color and dual
      fusion fluorescence in situ hybridization is a more reliably sensitive and
      practicable method for monitoring MRD in patients with CML after allo-HSCT, and
      can be used in detection of chromosome sample and blood or bone marrow smears.
      Dynamic detection of bcr/abl fusion gene level by FISH may predict disease
      changes and guide individual therapy.

PMID- 16800947
TI  - [Expressions of homing-related adhesion molecules in hematopoietic
      stem/progenitor cells derived from human placenta, umbilical cord arterial and
      venous blood].
AB  - The aim of this study was to evaluate the homing capabilities of hematopoietic
      stem/progenitor cells (HSPCs) derived from human placenta tissues (PT). Single
      cell suspension of human PT was prepared by mechanical method. The expression
      levels of homing-related adhesion molecules (HRAM) including CD11a, CD49d, CD44,
      CD49e, CD62L and CD54 on CD34(+) cells and the percentages of CD34(+) cells and
      their subpopulations in nucleated cells (NC) from fresh human PT, umbilical cord
      arterial blood (UCAB) and umbilical cord venous blood (UCVB) were detected by
      using flow cytometry. The results showed that the percentage of CD34(+) cells and
      CD34(+)CD38(-) cells in placenta were higher than those in UCAB and UCVB. There
      were no significant difference in percentage of HSPC between UCAB and UCVB.
      Placenta-derived CD34(+) cells strongly expressed CD11a, CD49d, CD44, CD49e and
      CD54, among which expression levels of CD49e and CD54 on placenta-derived CD34(+)
      cells were significantly higher than those on UCAB and UCVB-derived CD34(+)
      cells. While the percentage of CD34(+)CD62L(+) cells in placenta was only lower
      than that in UCVB. It is concluded that human placenta is rich in HSPC. Moreover,
      the expression levels of most HRAM in CD34(+) cells from PT are higher than those
      from UCAB and UCVB or are close to them. It suggested that HSPCs derived from PT
      might have stronger homing capabilities than those from UCB.

PMID- 16800948
TI  - [Molecular basis of partial D phenotypes in Chinese].
AB  - To investigate the molecular basis of partial D phenotypes in Chinese, D variants
      with weak D expression was screened by using indirect anti-human globulin test
      (IAT) method, the polymerase chain reaction-sequence specific primer (PCR-SSP)
      method was employed to amplify RHD specific exons and their flanking regions. The
      amplification products were sequenced directly to determine the molecular basis
      of D variants. The results showed that ten cases of partial D phenotypes,
      including one case of D Va (Kou.), one case of D Va (Hus.), one case of D Va-like
      (YH.), and seven cases of D VI type III, were detected from 22 cases of weak D
      phenotype respectively. All ten cases of partial D phenotypes had one RHD allele
      deleted. In conclusion, the molecular basis of ten cases of partial D phenotype
      was confirmed, including D Va (Kou.) and D Va-like (YH.) phenotypes reported
      firstly in Chinese population.

PMID- 16800949
TI  - [Regularity of sugar-uptake in human red blood cells].
AB  - Lyophilization of human red blood cells has important significance in clinical
      application. Some sugars, especially trehalose, can be more tolerant of some
      organism or cells to dry environments, But, how to bring sugars into cells is a
      challenge. This study was aimed to investigate the regularity of sugar-uptake in
      human red blood cells. The absorption rate of trehalose and glucose in red blood
      cells, free hemoglobin level and erythrocyte deformation index were determined at
      different incubation temperature (4, 25 and 37 degrees C), different sugar
      concentration (0, 0.2, 0.4, 0.6, 0.8 and 1 mol/L) and different incubation time
      (1, 3, 5, 7 and 9 hours). The results showed that with increase of temperature
      and extracellular sugar concentration, the uptake of sugar in red blood cells
      also increased, the intracellular trehalose and glucose concentrations were over
      30 mmol/L and 40 mmol/L respectively. The effects of incubation time on uptake of
      trehalose and glucose were different. With prolonging of incubation time, the
      uptake of trehalose showed firstly increase and then decrease, however, the
      uptake of glucose showed a constant increase. But the loading process had side
      effect on free hemoglobin and maximum deformation index (MAXDI) of red blood
      cells, especially for trehalose, which mainly come from high osmotic pressure. It
      is concluded that the uptake of sugars in red blood cells is closely dependent on
      incubation temperature, extracellular sugar concentration and incubation time. In
      certain condition, the efficiency of sugar uptake is very high, but this process
      also damages red blood cells so as to affect the application of sugars in
      lyophilization of red blood cells. The research in the future should focus on how
      to deal with the relation between cell injury and uptake efficiency of sugar in
      red blood cells.

PMID- 16800950
TI  - [Effect of beta-lactam antibiotics in drug-induced hemolysis].
AB  - The study was purposed to evaluate synergistic effect of beta-lactam antibiotics
      in drug-induced hemolysis. The general information, including primary diseases,
      therapeutic drugs, infection pathogens in 6 patients with pulmonary infection and
      unknown reason anemia were integrated and analyzed. The leukocyte and
      reticulocyte counts, total bilirubin (TB), direct bilirubin (DB), fasting blood
      glucose (Glu in peripheral blood) were all determined by conventional method. At
      the same time, the erythrocyte direct antiglobulin test (DAT), complement
      fixation test (CFT), cell culture and smear examination were carried out. The
      antibodies in plasma were also detected by indirect antiglobulin test (IAT). The
      result showed that levels of WBC, TB, DB, Glu and reticulocyte in six patients
      treated with beta-lactam antibiotics were raised remarkably. DAT was strongly
      positive, but no RBC antibodies were detected in the plasma by IAT. The binding
      of red cells by monocytes or lymphocytes was great, and the hemolysis of red
      cells by alexin not appeared. After stopping above-mentioned beta-lactam
      antibiotic administration, patient's WBC, TB, DB, and Glu levels returned to
      normal values. Furthermore, DAT test result turned to negative. It is concluded
      that beta-lactam antibiotics lead to drug-induced hemolysis by non-specific
      adsorption of some proteins onto RBC surface, and their proteins may be
      considered as direct cause for this hemolysis.

PMID- 16800951
TI  - [FUT3 gene polymorphism associated with Lewis blood group in Chinese Zhejiang
      population].
AB  - To investigate the alpha-1, 3/4-fucosyltransferase gene (FUT3) polymorphism
      associated with Lewis blood group in Zhejiang population, the Lewis phenotypes of
      183 random samples from Chinese blood donors in Zhejiang province were identified
      by standard serological techniques. The entire coding region of FUT3 gene were
      amplified by PCR from genomic DNA of 39 Lewis negative and 9 Lewis positive
      phenotype samples and sequenced directly. The haplotypes of FUT3 allele were
      identified by TOPO cloning sequencing method. The results showed that the
      frequency of true Le (a-b-) phenotype in Zhejiang population was 10.4% according
      to serological and molecular biological methods. Five nucleotide acid variant
      sites (59T > G, 202T > C, 314C > T, 508G > A and 1067T > A) were detected in all
      48 sequencing samples. Besides the wild type Le allele, 2 common (le(59, 1067)
      and le(59, 508) and 3 rare non-functional le alleles (le(59), le(1067) and
      le(202, 314) were found in this population. In conclusion, the polymorphism of
      non-functional FUT3 allele was found to be relatively variable in Chinese
      Zhejiang population.

PMID- 16800952
TI  - [Trehalose loading red blood cells and freeze-drying preservation].
AB  - This study was aimed to investigate the feasibility of cryopreserving red blood
      cells (RBCs) by loading with trehalose and to evaluate the effect of trehalose on
      lyophilized RBCs. Based on the thermal properties of RBC plasma membrane, the
      RBCs were incubated in 0.8 mol/L trehalose solution at 37 degrees C for 7 hours,
      and RBCs incubated in phosphate-buffered saline were used as control. The
      morphology of RBCs was observed by light and scanning electron microscopy, the
      hemolysis rate of loaded RBCs was detected by using cyanohemoglobin kit, the
      intracellular trehalose levels were assayed by sulfate anthrone method, the
      intracellular ATP and 2, 3-DPG levels were determined by bioluminescence assay
      and 2, 3-DPG kit respectively, meanwhile the deformation and osmotic fragility of
      RBCs were measured. The results showed that the intracellular trehalose
      concentration was 36.56 +/- 7.95 mmol/L, the electronical microscopic images of
      trehalose-loaded RBCs showed the membrane integrity, the hemolysis rate in
      trehalose-loaded RBCs was 15.663 +/- 3.848%, while hemolysis rate in controlled
      RBC was 5.03 +/- 1.85% (P < 0.05). Maximum index of deformation in trehalose
      loaded RBC was 0.0289 +/- 0.00738, while maximum index of deformation in control
      group was 0.1200 +/- 0.0121 (P < 0.05), The level of ATP in trehalose-loaded RBC
      was 2.67 +/- 0.54 micromol/gHb, while the level of ATP in control group was 5.22
      +/- 1.10 micromol/gHb (P > 0.05). Osmotic fragility data showed that trehalose
      exerted osmotic protection on RBC. During loading period the level of 2, 3-DPG in
      trehalose-loaded RBC was maintained close to the level in control. When trehalose
      loaded RBCs were lyophilized and rehydrated, the recovery rate of hemoglobin was
      about 46.44 +/- 4.14% and that in control was 8.33 +/- 2.34% (P < 0.001). The
      recovery rate of hemoglobin of trehalose-loaded RBC was higher than that of
      control. It is concluded that trehalose can be integrated in the membrane of RBC
      in lyophilization state, maintain the integrity of RBC membrane, and
      significantly enhance the recovery rate of hemoglobin of cryopreserved RBCs.
      Cryopreserving RBCs by loading with trehalose is feasible.

PMID- 16800953
TI  - [Ph+ acute lymphoblastic leukemia combined with lung and brain invasive
      aspergillosis].
AB  - This study was aimed to investigate the clinical features and therapy of Ph(+)
      acute lymphoblastic leukemia (Ph(+)ALL) combined with invasive aspergillosis. A
      series of examination, including routine blood and bone marrow picture analysis,
      chest roentgenography, cranial computerized tomography and detection of cell
      genetics etc were carried out for a Ph(+)ALL patient combined with invasive
      aspergillosis. This patient received chemotherapy with DVCP, idarubicin and
      imatinib mesylate and was treated with sporanox and amphotericin B (Amb;
      including Amb-L) and cerebrotomy for drainage because the invasive aspergillosis
      occurred during myelosuppression. The results showed that patient gained complete
      remission and the invasive aspergillosis was controlled successfully. It is
      concluded that patient with Ph(+)ALL has poor prognosis despite intensive
      conventional chemotherapy, imatinib mesylate may prove to be an effective
      treatment for Ph(+)ALL. Because detection rate of the fungus is very low,
      itraconazole in combination with surgical excision of focus is the best treatment
      of lung and brain invasive aspergillosis.

PMID- 16800954
TI  - [Evaluation of two methods for counting residual white blood cells in
      thrombocytaphoresis concentrates].
AB  - To evaluate flow-cytometry and Nageotte method for counting residual WBC in
      thrombocytaphoresis concentrates, their accuracies were determined by dilution
      studies separately; the repeatability was determined by measuring the interassay
      coefficient of variation for 14 replicates of a sample with known leukocyte
      concentration. 102 samples of leukocyte-depleted thrombocytaphoresis concentrates
      were detected by the above mentioned two methods, and the results were compared
      each other. The results showed that no difference was observed between two
      methods over a range of leukocyte concentrations from 0.8 to 10 WBC/microl (P >
      0.05). In conclusion, flow-cytometry and Nageotte methods can be used for quality
      control of WBC-reduced blood components.

PMID- 16800955
TI  - [Technique of detection of hepatitis C core antigen used in safety blood
      transfusion].
AB  - This study was purposed to investigate the feasibility to screen donor with HCV
      infection by means of HCV-cAg ELISA. The first and repeat assays were performed
      for detection of serum anti-HCV in 8677 donor's serum specimens from January 2003
      to December 2005. All serum anti-HCV specimens with positive anti-HCV from first
      and repeat assays were finally identified by using HCV-cAg ELISA and HCV RT-PCR
      methods. The results showed that only 5 serum specimens were positive anti-HCV by
      HCV-cAg ELISA identification in 29 specimens including 15 specimens with positive
      ant-HCV in first assays and 14 specimens with positive anti-HCV in repeat assays,
      the positive rate detected by HCV cAg ELISA was 17.24%. 5 serum specimens were
      positive anti-HCV by HCV RT-PCR detection also in 29 specimens mentioned above,
      the positive rate detected by HCV RT-PCR was 17.24% too. It is concluded that
      sensitivity of HCVcAg ELISA is similar to HCV RT-PCR and may be useful for the
      early diagnosis of hepatitic C or used as a reliable method to screen donor with
      HCV infection in blood transfusion medicine.

PMID- 16800956
TI  - [Application of spectral karyotyping in leukemia--review].
AB  - Spectral karyotyping (SKY) is a novel cytogenetic technique, has been developed
      to unambiguously display and identify all 24 human chromosomes at one time
      without a priori knowledge of any abnormalities involved. SKY discerns the
      aberrations that can not be detected very well by conventional banding technique
      and fluorescent in situ hybridization (FISH). So SKY is hyper-accurate,
      hypersensitive, and hyper-intuitional. In this paper the basic principle of SKY
      technique and its application in leukemia cytogenetics were reviewed.

PMID- 16800957
TI  - [Progress of studies on animal model of immune thrombocytopenic purpura--review].
AB  - Human ITP clinical trials have been performed based on observations of clinical
      uses of drugs, other than on mechanism studies in preclinical models, many
      studies were stopped because of unexpected complications. So there was need to
      develop ideal animal model of ITP to improve the understanding of the
      pathophysiology and the mechanisms of action of therapeutics. In this review, the
      history of animal models of ITP was retrospected, two modeling methods inducing
      passive and active models, especially transgenic rice model which can more
      accurately represent human disease pathophysiology, and their application in
      study of ITP were summarized. An animal model for human immune thrombocytopenia
      allows detailed studies of the mechanism, kinetics, and therapy of human immune
      thrombocytopenia.

PMID- 16800958
TI  - [KIRs on human NK cells and in relation with HLA class I antigen--review].
AB  - The interaction of killer cell immunoglobin-like receptors (KIR) with HLA
      molecules has particular relevance to the genetics, immune responses and
      allogeneic stem cell transplantation. The genes of KIR and HLA are located in
      different chromosomes and segregate independently. The repertoire of KIR
      molecules varies among NK cells and is determined by the KIR genotype. The HLA
      genotype has only subtle impact on the KIR phenotype. Three major HLA specificity
      groups are recognized by KIRs. Donor versus recipient NK-cell alloreactivity,
      when recipients lack HLA ligand for their donor inhibitory KIR, can benefit
      allogeneic stem cell transplantation, especially the HLA haploidentical
      hematopoietic stem cell transplantation. The outcome of stem cell transplantation
      can be best predicted by the presence of KIRs on the donor's NK cells and the
      absence of corresponding KIR ligand in the recipient's HLA repertoire-a receptor
      ligand model. In this paper the interaction of KIR and HLA in hematopoietic stem
      transplantation, the genetic basis of KIR and HLA, the relation of KIR expression
      on NK cells with HLA and the role of KIR and HLA in immune responses were
      reviewed.

PMID- 16800959
TI  - [Role of B-cell-activating-factor in immune regulation--review].
AB  - B cell activating factor (BAFF) is one of the TNF family member, regulates the
      survival and maturation of B lymphocyte. BAFF binds to three receptors: BCMA,
      TACI and BAFF-R. In recent years, studies have revealed important roles of BAFF
      and its receptors in immune regulation of antibody isotype switching, germinal
      center maintenance, and T cell co-stimulation, that may provide new drugs in the
      future for the treatment of autoimmune disorders, lymphoma and B cell
      immunodeficiencies. Therefore, the structure, expression, receptors, biological
      function and clinical application of BAFF are briefly summarized in this review.

PMID- 16800960
TI  - Smoking history: tumor biology and clinical pharmacokinetic implications in
      patients with lung cancer.

PMID- 16800962
TI  - Clinical development of SRC tyrosine kinase inhibitors in lung cancer.
AB  - Src tyrosine kinases regulate a large number of important mechanisms in normal
      and cancerous cells, are overexpressed in a broad range of tumors including lung
      cancer, and thus represent a potential target for cancer therapy. Preclinical
      experiments indicate that small-molecule inhibitors of Src block tumor growth,
      metastasis, and angiogenesis. Phase I data from healthy volunteers also suggest
      that inhibitors of Src prevent bone resorption. Several phase II trials with
      small-molecule inhibitors of Src are under way or have been initiated in lung
      cancer and in other malignancies, as discussed herein.

PMID- 16800963
TI  - Pharmacodynamic separation of epidermal growth factor receptor tyrosine kinase
      inhibitors and chemotherapy in non-small-cell lung cancer.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) given
      concurrently with chemotherapy do not improve patient outcomes compared with
      chemotherapy alone in advanced-stage non-small-cell lung cancer (NSCLC). One
      potential explanation for this lack of benefit is a negative interaction or
      antagonism between chemotherapy and EGFR TKIs when delivered concomitantly.
      Support for this line of reasoning is provided by preclinical data demonstrating
      that EGFR TKIs induce primarily a cytostatic effect resulting from a G1 cell
      cycle arrest in cell lines with wild-type EGFR, reducing cell cycle phase
      dependent activity of chemotherapy, whereas they induce apoptotic cell death in
      tumors with EGFR-activating mutations. Because the great majority of NSCLC tumors
      consist of wild-type EGFR, sequence-specific interactions of EGFR
      TKI/chemotherapy combinations might negatively influence the efficacy of these
      regimens in patients with NSCLC. Further evidence is provided by EGFR mutational
      analysis in patient tumor specimens from the TRIBUTE study. Herein we provide the
      preclinical and clinical rationale for studies examining the concept of
      pharmacodynamic separation as a means for overcoming hypothesized antagonism of
      EGFR TKIs and chemotherapy.

PMID- 16800964
TI  - Smoking history and epidermal growth factor receptor expression as predictors of
      survival benefit from erlotinib for patients with non-small-cell lung cancer in
      the National Cancer Institute of Canada Clinical Trials Group study BR.21.
AB  - BACKGROUND: Erlotinib is an oral, reversible inhibitor of the HER1/epidermal
      growth factor receptor (EGFR) tyrosine kinase. A survival advantage for erlotinib
      compared with placebo was demonstrated in the National Cancer Institute of Canada
      Clinical Trials Group study BR.21, a randomized double-blind study of 731
      patients with advanced-stage non-small-cell lung cancer. PATIENTS AND METHODS: In
      this retrospective, exploratory investigation, univariate and multivariate
      analyses of survival of the 311 patients with available EGFR status by
      immunohistochemistry and known smoking history were performed to determine which
      factor might be more important for predicting clinical outcome. RESULTS: A
      marginally significant interaction was observed between smoking history and
      treatment (P = 0.054). The hazard ratios (HRs) were 0.42 among never-smokers and
      0.87 for smokers, indicating that erlotinib was beneficial in both subsets but
      more effective in patients who had never smoked. The HRs for patients with EGFR
      positive and EGFR-negative tumors were 0.65 and 0.83, respectively; however, the
      interaction between EGFR status and treatment was not significant in univariate
      or multivariate analyses. Patients with EGFR-positive tumors who never smoked had
      the greatest survival benefit from erlotinib relative to placebo (HR, 0.28; P =
      0.0007). CONCLUSION: These data suggest that never-smokers and patients with EGFR
      positive tumors might experience an enhanced benefit from erlotinib compared with
      placebo but that smoking history might be more predictive of survival benefit
      than EGFR expression. Subset analyses of ever-smokers revealed significant
      survival advantages for men and patients with squamous cell histology. Male ever
      smokers with squamous cell non-small-cell lung cancer derived a significant
      survival benefit from erlotinib (HR, 0.66; P = 0.015) despite a very low tumor
      response rate.

PMID- 16800966
TI  - Second-line chemotherapy with a modified schedule of docetaxel in elderly
      patients with advanced-stage non-small-cell lung cancer.
AB  - PURPOSE: In patients with advanced-stage non-small-cell lung cancer (NSCLC)
      pretreated with chemotherapy, docetaxel 75 mg/m2 every 3 weeks prolongs survival
      compared with best supportive care alone or chemotherapy with ifosfamide or
      vinorelbine. Neutropenia is the dose-limiting toxicity of this schedule, and thus
      limits its use in elderly patients. Therefore, we studied a modified schedule of
      docetaxel in order to reduce the toxicity of this regimen and to improve the
      compliance to treatment in an elderly population, while maintaining the same dose
      intensity of the original regimen. PATIENTS AND METHODS: Thirty-three elderly
      patients (aged > or = 70 years) with advanced-stage NSCLC, Eastern Cooperative
      Oncology Group performance status 0-2, and a median age of 74 years (range, 70-83
      years) who had progressed after 1 line of chemotherapy were treated with
      docetaxel 37.5 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 courses.
      RESULTS: Seven of 33 patients (21.2%; 95% confidence interval, 8.98%-38.91%)
      exhibited a partial response (according to the intent-to-treat analysis), 12
      patients (36.3%) exhibited stable disease, and 14 patients (42.4%) exhibited
      progression. Grade 3 (National Cancer Institute Common Toxicity Criteria)
      neutropenia and anemia were observed in 9% and 3% of patients, respectively. The
      main nonhematologic toxicity consisted of grade 3 nausea/vomiting, diarrhea, and
      asthenia in 6% of patients each, and grade 3 nail toxicity in 3% of patients.
      CONCLUSION: Our modified schedule of docetaxel is an active and well-tolerated
      second-line treatment in elderly patients with advanced-stage NSCLC and has a
      favorable toxicity profile.

PMID- 16800965
TI  - Prognostic role of protease-activated receptors 1 and 4 in resected stage IB non
      small-cell lung cancer.
AB  - BACKGROUND: Protease-activated receptor (PAR)-1 and PAR-4 are involved in
      extracellular matrix invasion and angiogenesis. PATIENTS AND METHODS: A series of
      60 resected stage IB non-small-cell lung cancers (NSCLCs), including 30
      adenocarcinomas (ADCs) and 30 squamous cell carcinomas (SCCs), were processed by
      immunohistochemistry with antibodies to PAR-1, PAR-4, vascular endothelial growth
      factor (VEGF), and CD34. RESULTS: Protease-activated receptor-1 was expressed in
      37 cases (62%) and PAR-4 in 39 (65%). Adenocarcinomas were significantly more
      positive than SCC for PAR-1 (17 vs. 8 cases) and PAR-4 (10 vs. 5 cases). Vascular
      endothelial growth factor was expressed in 42 cases (70%): 22 ADC and 20 SCC. A
      significant correlation emerged between PAR-1 and/or PAR-4 expression and VEGF
      but not with microvessel density. Median follow-up was 38 months; actuarial 5
      year survival was 43%. At univariate analysis, 3-year survival was shorter in
      patients expressing PAR-4 versus negative cases (29% vs. 60%; P = 0.002). In 46
      patients expressing PAR-1 and/or PAR-4, 3-year survival was 30% versus 68% in 14
      patients with no PAR expression (P = 0.002). A trend toward shorter 3-year
      survival was seen in PAR-1-positive versus PAR-1-negative cases (34% vs. 46%; P =
      0.06). Multivariate analysis identified expression of PAR-1 and/or PAR-4 as an
      independent prognostic factor for reduced survival in resected stage IB NSCLC.
      CONCLUSION: Expression of PAR-1 and PAR-4 in early-stage NSCLC could be included
      in a molecular algorithm for the selection of patients eligible for adjuvant
      studies.

PMID- 16800967
TI  - Gefitinib monotherapy in chemotherapy-naive patients with inoperable stage III/IV
      non-small-cell lung cancer.
AB  - BACKGROUND: Gefitinib is an orally active epidermal growth factor receptor
      tyrosine kinase inhibitor with activity in previously treated patients with
      advanced-stage non-small-cell lung cancer (NSCLC). However, little is known of
      its activity as monotherapy in chemotherapy-naive patients. This phase II study
      (1839IL/0456) evaluated first-line gefitinib in patients with advanced-stage
      NSCLC. PATIENTS AND METHODS: Eligible patients with proven inoperable stage
      III/IV NSCLC, no previous chemotherapy, and a performance status of 0-2 received
      gefitinib 250 mg per day until disease progression. Patient reevaluation was
      performed by radiography and computed tomography at regular intervals. RESULTS:
      Fifty-eight of 59 patients were available for analysis. Response rate (complete
      plus partial responses) was 5% (3 of 58 patients); 40% (23 of 58 patients)
      exhibited stable disease (overall disease control rate, 45% [26 of 58 patients]).
      Median progression-free survival was 7 weeks, and median overall survival was 29
      weeks. All responders were women and/or nonsmokers with adenocarcinoma or
      bronchoalveolar carcinoma. Gefitinib treatment was well tolerated; skin
      toxicities occurred in 71% of patients, including severe skin toxicities in 2
      patients, and mild to moderate diarrhea occurred in 50% of patients. CONCLUSION:
      Gefitinib monotherapy has some efficacy in chemotherapy-naive patients with
      advanced-stage or metastatic NSCLC. However, activity seems to be limited to
      particular patient groups.

PMID- 16800968
TI  - Decreased fragile histidine triad gene messenger RNA expression in lung cancer.
AB  - BACKGROUND: The fragile histidine triad (FHIT) gene is located at 3p14.2, a
      region frequently lost in various tumor types. Lack of FHIT expression has been
      found to occur frequently in multiple tumor types including lung cancer. We have
      investigated FHIT messenger RNA (mRNA) levels and other clinicopathologic data,
      including FHIT and p21 expression in lung cancer. PATIENTS AND METHODS: The study
      included 97 lung cancer cases. The FHIT mRNA levels were quantified by
      quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using
      LightCycler. RESULTS: The FHIT/glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      mRNA levels were decreased in tumor tissues from lung cancer (13.844 +/- 33.047)
      compared with adjacent nonmalignant lung tissues (195.763 +/- 678.469; P <
      0.0001). No significant difference in FHIT/GAPDH mRNA levels was found among age,
      T status, or lymph node metastasis. The FHIT/GAPDH mRNA level was less in
      squamous cell carcinoma (0.144 +/- 0.246), a smoking-related cancer, than in
      adenocarcinoma (0.72 +/- 1.321; P = 0.0355). FHIT/GAPDH mRNA levels were
      correlated with FHIT protein (P = 0.0139) and p21 protein (P = 0.0484) expression
      by immunohistochemistry. The prognosis for patients with lung cancer with low
      FHIT/GAPDH levels (< 0.26; n = 57) was significantly worse than in the patients
      with high FHIT/GAPDH levels (> 0.26; n = 40; log-rank test, P = 0.0404).
      CONCLUSION: Using the LightCycler RT-PCR assay, decreased FHIT gene expression
      might occur early and play an important role in lung tumorigenesis and also
      correlate with the prognosis of lung cancer. However, further studies are needed
      to confirm the impact of FHIT in the biologic behavior of the tumor.

PMID- 16800969
TI  - PIONEER: a phase III randomized trial of paclitaxel poliglumex versus paclitaxel
      in chemotherapy-naive women with advanced-stage non-small-cell lung cancer and
      performance status of 2.

PMID- 16800970
TI  - Hormonal therapy: still much to learn.

PMID- 16800971
TI  - Risk of cancer treatment-associated bone loss and fractures among women with
      breast cancer receiving aromatase inhibitors.
AB  - BACKGROUND: Aromatase inhibitors (AIs) are a novel hormonal therapy for patients
      with breast cancer. However, AIs can cause bone loss by blocking estrogen
      production. This study aims to assess the association between AIs and treatment
      related bone loss in a large managed-care population of women with breast cancer.
      PATIENTS AND METHODS: With use of medical and pharmacy claims, data from > 5
      million beneficiaries between January 1, 1998, and January 31, 2005, we
      identified 12,368 patients with > or = 2 breast cancer claims in a 6-month period
      who also had no bone metastases and no previous osteoporosis or fracture claims.
      Patients who had received antiestrogen (eg, tamoxifen) therapy were also
      excluded. One thousand three hundred fifty-four patients receiving an AI
      (anastrozole, exemestane, or letrozole) were compared with 11,014 controls who
      did not receive an AI with respect to their risk of bone loss. The observation
      start date for the AI and control groups was defined as the service date of the
      first AI claim and breast cancer claim, respectively. The endpoints include (1)
      bone loss, consisting of osteoporosis or osteopenia, and (2) clinical fractures.
      RESULTS: The univariate analysis found that the prevalence of bone loss was 8.7%
      in the AI group versus 7.1% in the control group, resulting in a significant
      relative risk of 1.3 (95% confidence interval [CI], 1.1-1.6; P = 0.01). The
      prevalence of bone fracture was also significantly increased in the AI group
      compared with the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI,
      1.2-1.6, P = 0.001). Multivariate Cox proportional hazards regressions showed
      that after adjusting for age and comorbidities, the risk of bone loss remained
      significantly higher in the AI group than in the non-AI group, with a 27% (95%
      CI, 4%-55%; P = 0.02) and 21% (95% CI, 3%-43%; P = 0.02) increase in the risk of
      bone loss and fractures, respectively. CONCLUSION: This retrospective
      longitudinal analysis of a large cohort of patients with breast cancer
      corroborates previous findings from smaller clinical trials and demonstrates that
      AI therapies carry an increased risk of bone loss. Monitoring and treatment
      management strategies to reduce bone loss risk are warranted in women receiving
      an AI for breast cancer.

PMID- 16800972
TI  - Disease-specific survival in patient-detected breast cancer.
AB  - BACKGROUND: Patient-detected breast cancer is not well described, and its
      association with survival is not known. PATIENTS AND METHODS: Initial breast
      cancer detection methods were extracted from patient chart notes in a registry
      cohort of women aged 40-93 with primary invasive breast cancer seen at the
      community-based regional cancer center between 1990 and 1999 (N = 2228). Patients
      were followed for vital status and recurrence (current as of 2003/2004) with a
      mean follow-up of 7.6 years. Physician-detected breast cancers were excluded from
      the analysis (n = 231). RESULTS: Forty-six percent of cases were patient detected
      (n = 1019), and 54% were mammography detected (n = 1209). Those with patient
      detected disease received more aggressive treatment (combined radiation and
      chemotherapy; 49% vs. 23%; P < 0.001) and were twice as likely to have a modified
      radical mastectomy (41% vs. 20%; P < 0.001). Patient-detected cases were more
      likely to have a disease recurrence (5-year recurrence rate: 13% vs. 6%; log-rank
      test, 30.51; P < 0.001) and were more likely to die of disease (5-year disease
      specific mortality rate: 8% vs. 3%; log-rank test, 34.7; P < 0.001). In a Cox
      proportional hazards model, detection method was not associated with risk of
      breast cancer-related death. CONCLUSION: Patient-detected breast cancer appears
      to be a more virulent form of breast cancer than mammography-detected breast
      cancer with higher recurrence and mortality risk despite more aggressive
      treatment.

PMID- 16800973
TI  - Phase II study of weekly docetaxel and capecitabine in patients with metastatic
      breast cancer.
AB  - PURPOSE: This phase II study evaluated the safety and efficacy of weekly
      docetaxel and capecitabine in patients with metastatic breast cancer. PATIENTS
      AND METHODS: Thirty-nine patients with metastatic breast cancer received 30 mg/m2
      of docetaxel on days 1, 8, and 15 in combination with capecitabine 800 mg/m2
      twice daily on days 1-21, repeated every 28 days. RESULTS: The median number of
      treatment cycles was 4 (range, 1-20 cycles). Grade 3 toxicities per patient were
      asthenia (n = 7; 18%), diarrhea (n = 7; 18%), nausea/vomiting (n = 5; 13%),
      stomatitis (n = 5; 13%), neutropenia (n = 5; 13%), and hand-foot syndrome (n = 4;
      10%). There were only 2 grade 4 toxicities, febrile neutropenia and pulmonary
      embolism. The overall response rate was 44% (95% confidence interval (CI), 28%
      60%), median duration of response was 9.1 months (95% CI, 6.2-12 months), and
      median time to progression was 5.5 months (95% CI, 3.7-7.3 months). CONCLUSION:
      Weekly docetaxel with capecitabine was active with acceptable toxicities.
      Additional trials to define the optimal schedule of docetaxel and capecitabine
      are justified.

PMID- 16800974
TI  - Prognostic significance of disseminated tumor cells as detected by quantitative
      real-time reverse-transcriptase polymerase chain reaction in patients with breast
      cancer.
AB  - BACKGROUND: In this study we have validated the feasibility of detecting
      disseminated tumor cells (DTC) by real-time reverse-transcriptase polymerase
      chain reaction (RT-PCR) analysis. Bone marrow samples from a large cohort of
      patients with breast cancer were analyzed for the presence of DTC by
      immunocytochemistry (ICC) or a molecular-based method. PATIENTS AND METHODS: Bone
      marrow samples were collected from 170 patients with breast cancer with stage I
      IV disease before the initiation of any local or systemic treatment. Staining for
      cytokeratin (CK)-positive cells was performed with the Epimet kit. Disseminated
      tumor cells were also quantified by measuring relative gene expression for CK19
      and mammaglobin (MAM) using a quantitative RT-PCR detection method. The mean
      follow-up time was 30 months. Kaplan-Meier analysis was used for predicting
      overall survival. RESULTS: Despite an excellent quantitative correlation and
      qualitative concordance between ICC and RT-PCR, survival analysis suggested an
      improved prognostic significance of DTC as detected by quantitative RT-PCR.
      Univariate survival analysis computed a relative risk of death of 2.87 for women
      with ICC-positive cells in the bone marrow, as compared with those without
      positive cells. The relative risk for women with RT-PCR-positive bone marrow was
      even higher: 3.5 (CK19) and 3.39 (MAM). In multivariate analysis, bone marrow
      CK19 was a stronger prognostic factor than bone marrow ICC. CONCLUSION: Reverse
      transcriptase polymerase chain reaction-detected DTC is shown to be
      prognostically significant in untreated patients with breast cancer. Furthermore,
      it seems to be a more sensitive method for detecting DTC in bone marrow samples
      when compared with ICC.

PMID- 16800975
TI  - Concordance between central and local laboratory HER2 testing from a community
      based clinical study.
AB  - BACKGROUND: Women with HER2-overexpressing breast cancer have an unfavorable
      prognosis. Trastuzumab improves survival when combined with chemotherapy in the
      first-line treatment of patients with HER2-overexpressing metastatic breast
      cancer and decreases the rate of disease relapse by 52% and the rate of death by
      33% in women with HER2-overexpressing early-stage breast cancer. HER2 testing can
      be performed using immunohistochemistry (IHC) or fluorescence in situ
      hybridization (FISH) and can be performed at local pathology laboratories or at
      central/reference laboratories. Because of the significant benefit seen with
      trastuzumab, it is critical to accurately identify women most likely to benefit.
      The method and the location of HER2 testing contribute to the accuracy of test
      results. PATIENTS AND METHODS: HER-First, a prospective, community-based, phase
      IV study of first-line trastuzumab/taxane therapy, enrolled patients with HER2
      overexpressing metastatic breast cancer. Retesting of all tumor specimens by HER2
      IHC and FISH at a high-volume, experienced laboratory was required. RESULTS:
      Concordance between local and central laboratory HER2 IHC testing was highest for
      local IHC 3+ samples (n = 377; 77%) and lowest for IHC 2+ samples (n = 184; 26%).
      Thirty-three percent of samples testing IHC 2+ at a local laboratory tested FISH
      positive at the central laboratory. Concordance between HER2 IHC and FISH results
      was higher when both tests were performed at the central laboratory. CONCLUSION:
      Accurate HER2 test results are critical to identify patients who are appropriate
      candidates for trastuzumab, a therapy with significant clinical benefits in HER2
      overexpressing breast cancer. These data show that HER2 testing is most accurate
      when performed at a high-volume reference laboratory.

PMID- 16800976
TI  - Inadvertent use of aromatase inhibitors in patients with breast cancer with
      residual ovarian function: cases and lessons.
AB  - Aromatase inhibitors (AIs) are important adjunctive therapy for postmenopausal
      women with hormone receptor-positive, early-stage breast cancer. At the present
      time, AIs have no role for the management of breast cancer in premenopausal
      women. We report on several cases of the inadvertent use of AI therapy among
      women with residual ovarian function. A common experience in these cases was the
      onset of chemotherapy-related amenorrhea before initiation of AI therapy, which
      confounded assessment of true menopausal status. We believe clinicians should be
      aware of the potential ovarian reserve among women with treatment-related
      amenorrhea so as to avoid use of AI therapy in patients in whom there is
      uncertainty about menopausal status.

PMID- 16800977
TI  - A durable complete remission between two isolated presentations of metastatic
      breast cancer, the second with intracardiac disease.
AB  - We report a case of a postmenopausal patient with hormone receptor-positive
      breast cancer who, while receiving tamoxifen, experienced relapse with isolated
      ovarian metastases 4.5 years after her primary treatment. After resection of her
      pelvic disease, she commenced anastrozole, and while receiving this, remained
      disease free for an additional 7.5 years before experiencing relapse again with
      isolated metastatic disease in an unusual location: intracardiac disease causing
      superior vena cava obstruction.

PMID- 16800978
TI  - Long-term clinical response in leptomeningeal metastases from breast cancer
      treated with capecitabine monotherapy: a case report.
AB  - Brain and leptomeningeal metastases from breast cancer carry a poor prognosis and
      are often less responsive to systemic therapy. It is often thought that systemic
      therapy has a minimal role in the management of central nervous system (CNS)
      metastases because of the impermeability of the blood-brain barrier. However,
      treatments directed to the CNS such as radiation or intrathecal chemotherapy are
      not effective in managing concurrent non-CNS metastases. We report the long-term
      control of a woman receiving capecitabine with brain and leptomeningeal
      metastases. After 3.7 years of capecitabine therapy after whole-brain radiation,
      the patient remains without neurologic symptoms or deficits, has no evidence of
      disease on neuroimaging studies, but has a persistent positive cytology. This
      case report demonstrates that, in principle, systemic therapy can provide long
      term complete responses for some patients with CNS metastases. The significance
      of persistent circulating tumor cells in the CNS in patients without evidence of
      disease is unclear but should be investigated further.

PMID- 16800979
TI  - Chemotherapy with taxanes in breast cancer during pregnancy: case report and
      review of the literature.
AB  - Two patients with breast cancer received docetaxel-containing chemotherapy as
      adjuvant or neoadjuvant therapy during pregnancy. The first pregnant patient
      began neoadjuvant therapy with doxorubicin/cyclophosphamide at 14 weeks of
      gestation. After 4 cycles of doxorubicin/cyclophosphamide and surgery, she
      received adjuvant docetaxel for 4 cycles. The second patient began neoadjuvant
      therapy with doxorubicin/docetaxel at 14 weeks of gestation and received 6
      cycles. The fetus of the first patient had hydrocephalus on ultrasound at 17
      weeks of gestation (before docetaxel therapy) that persisted on serial follow-up
      ultrasounds and spontaneously regressed over several months after delivery. No
      fetal malformations were detected in the second fetus. These 2 cases add to the
      existing data on the use of taxanes during pregnancy. Although the data are
      limited with case reports, pregnant patients with cancer can be treated with
      chemotherapy including taxanes during the second and third trimesters without
      significant risks to the fetus. Taxanes should not be excluded, if indicated, in
      pregnant patients with cancer.

PMID- 16800980
TI  - A case of chylous fistula after axillary dissection in breast-conserving
      treatment for breast cancer.
AB  - Chyle fistula is not a well-known complication of axillary dissection in patients
      with breast cancer. Although rare, this complication can occur as a result of
      anatomic variation of the thoracic duct and its venous anastomosis. Injury to the
      lateral terminating branches or lymphatic trunk, leading to retrograde chyle
      flow, is more likely than direct injury to the duct. We report a case of chylous
      fistula after axillary dissection in a patient with breast cancer, review the
      literature, and discuss the management of this rare complication.

PMID- 16800981
TI  - Pregnancy after the diagnosis of breast cancer.

PMID- 16800982
TI  - A randomized phase II study of docetaxel alone or in combination with PANVAC-V
      (vaccinia) and PANVAC-F (fowlpox) in patients with metastatic breast cancer (NCI
      05-C-0229).

PMID- 16800983
TI  - Abscess as initial presentation of pure primary squamous cell carcinoma of the
      breast.

PMID- 16800984
TI  - Status and prospect in preventing and treating HIV/AIDS with traditional Chinese
      medicine.

PMID- 16800985
TI  - Advance in basic and clinical research of Xuezhikang Capsule.

PMID- 16800986
TI  - Effects of Kanlijian on exercise tolerance, quality of life, and frequency of
      heart failure aggravation in patients with chronic heart failure.
AB  - OBJECTIVE: To observe the effects of conventional therapy combined with Kanlijian
      (KLJ) on exercise tolerance, quality of life and frequency of heart failure
      aggravation in patients with chronic heart failure (CHF). METHODS: Sixty CHF
      patients differentiated as sufferring from the syndrome of Xin-Shen Yang
      deficiency were included in the study and randomly assigned at the ratio of 2:1
      into the KLJ group (n = 39) and the control group (n = 21). All the patients were
      treated with conventional therapy of Western medicine, but to those in the KLJ
      group, KLJ was medicated additionally one dose daily with 24 wks as one
      therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM
      syndrome were observed after treatment. The indexes, including 6-minute walking
      distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade,
      hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before
      and after treatment were recorded and compared. Also the frequency of re
      admission due to aggravation of heart failure in one year's time were observed.
      RESULTS: (1) The efficacy on TCM syndrome, improvement on scores of TCM syndrome,
      therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior
      to those in the control group. (2) Hemodynamic indexes after treatment, left
      ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two
      groups had no significant difference, while left ventricular ejection fraction
      (LVEF) was increased significantly in the KLJ group, but with no obvious change
      in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in
      the KLJ group was significantly higher than that in the control group. (4) The 1
      year frequency of re-admission significantly decreased in the KLJ group.
      CONCLUSION: The adjuvant treatment of KLJ on the basis of Western conventional
      therapy can significantly improve CHF patients' exercise tolerance, quality of
      life and cardiac function, reduce the dosage of diuretic and digoxin needed, and
      decrease the re-admission frequency due to aggravation of heart failure.

PMID- 16800987
TI  - Effects of choleretics on bile compositions drained from patients with pigment
      gallstone.
AB  - OBJECTIVE: To provide evidence for three-level prevention of cholelithiasis by
      means of observing the effects of some choleretics on bile compositions drained
      from patients with pigment gallstone. METHODS: Twenty-seven patients suffering
      from primary pigment gallstones and having received treatment of
      choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were
      divided equally into three groups, and administered respectively with Lidanling
      (the LDL group), ursodesoxycholic acid (the UDA group) and combination of LDL and
      UDA (the LDL + UDA group) through oral intake (7 patients in each group).
      Besides, 6 post-operational patients got no treatment with any drug were
      allocated in the control group. Bile of all the patients was collected before
      treatment and on the 1, 3, 5, 7 th day after the treatment started to detect
      levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA),
      glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined
      bilirubin (UCB), concentration of calcium ion (Ca(2+)) as well as the bacterio
      genetic and endogenous beta-glucuronidase activity for comparing. RESULTS: Levels
      of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL +
      UDA group after treatment (P < 0.05), while those in the LDL group remained
      unchanged, showing an insignificant difference as compared with those in the
      control group. In the LDL group and the LDL + UDA group, TBIL gradually increased
      while UCB gradually decreased in the course of treatment (P < 0.05). Moreover,
      levels of Ca(2+) and endogenous beta-glucuronidase activity got significantly
      lowered (P < 0.05). CONCLUSION: Combined use of LDL and UDA could elevate levels
      of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment
      gallstone after bile drainage, lower levels of UCB and Ca(2+) and the activity of
      endogenous beta-glucuronidase in the bile, so as to reduce the possibility of
      stone formation of bile, and therefore, it could be used to prevent the
      production of pigment gallstone, especially to prevent post-operative recurrence
      of stones.

PMID- 16800988
TI  - Clinical study on Ganbi decoction in treating antituberculotic agent-caused liver
      injury.
AB  - OBJECTIVE: To study the effect and mechanism of Ganbi decoction (GBD) in treating
      patients with antituberculotic agent caused liver injury (ATB-LI). METHODS: One
      hundred and twenty-eight patients with ATB-LI were randomly assigned to the
      treated group (n = 66) and the control group (n = 62) with the envelop method.
      Meanwhile, 60 healthy persons were selected as the healthy control group. The
      treated group was treated by GBD one dose every day with the constituents
      modified depending on patients' symptoms, and the control group was treated with
      glucuronolactone tablets and inosine injection. One week was taken as one
      treatment course. The changes of clinical syndromes, physical signs, T-lymphycyte
      sub-groups and serum level of nitric oxide (NO) were observed before and after
      treatment and the recovery time of liver function was recorded. The outcome was
      compared with that in the healthy control group. RESULTS: In the treated group,
      28 patients (42.4%) were cured, 30 (45.5%) improved and 8 (12.1%) ineffectively
      cured, the total effective rate being 87.9% (58/66). In the control group, 17
      patients (27.4%) were cured, 24 (38.7%) improved, and 21 (33.9%) ineffectively
      cured, the total effective rate being 66.1% (41/62). The total effective rate in
      the treated group was significantly higher than that in the control group (P <
      0.05). Liver function was improved in both groups, recovery time in the treated
      group was 12.0 +/- 7.0 days, which was significantly shorter than that in the
      control group (16.0 +/- 8.0 days), showing significant difference between the two
      groups (P < 0.05). The levels of CD3, CD4 and CD8 were significantly higher and
      level of NO significantly lower in the two groups of patients than those in the
      healthy control group (P < 0.05), but these parameters were improved more
      significantly in the treated group after treatment, when compared with those
      before treatment or with those in the control group, all showing significant
      difference (P < 0.05). CONCLUSION: GBD could prevent ATB-LI, and its mechanism
      could be by way of reducing NO production induced by endotoxin of macrophage and
      stimulating the proliferation of T-lymphycyte to elevate immunity.

PMID- 16800989
TI  - Clinical study on effect of Xiaoyao Nose Drops in stopping episode of migraine.
AB  - OBJECTIVE: To observe the effect of Xiaoyao Nose Drops (XYND) in stopping episode
      of migraine. METHODS: Adopted was the randomized double-blinded placebo-controled
      method, with the 126 patients equally assigned to two groups, the treated group
      treated with XYND and the control group with placebo, and the therapeutic course
      was 30 days for all. The clinical total effective rate and effect in alleviating
      headache were observed. And hemorrheological parameters as well as the blood flow
      of the anterior cerebral artery (ACA), median cerebral artery (MCA) and posterior
      cerebral artery (PCA) were measured before and after treatment. RESULTS: The
      clinical total effective rate and headache alleviating rate in the treated group
      were 93.33% and 96.67% respectively, while those in the control group were 18.33%
      and 20.00% respectively, and comparison between the two groups showed significant
      difference (all P < 0.01). The blood viscosity (high, middle and low shear),
      plasma viscosity and fibrinogen got lowered significantly in the treated group
      after treatment, showing significant difference in comparison either with those
      before treatment or with those in the control group after treatment (P < 0.05 or
      P < 0.01). The velocity of blood flow in all cerebral arteries lowered
      significantly, also showing significant difference in comparison either with
      those before treatment or with those in the control group after treatment (P <
      0.05 or P < 0.01). CONCLUSION: XYND is effective in stopping the headache of
      patients with migraine, and worth applying in clinical practice.

PMID- 16800990
TI  - Effect of Wuye Decoction on lymphocyte phenotype in patients with non-small cell
      lung cancer.
AB  - OBJECTIVE: To investigate the effect of Chinese recipe, Wuye Decoction (WYD), on
      immune function in patients with non-small cell lung cancer (NSCLC). METHODS:
      Eighty-two patients of NSCLC with pathologically confirmed diagnosis, who had
      received operative treatment and completed the post-operational chemotherapy,
      were randomly assigned into 2 groups. Group A (42 cases) received WYD and Group B
      (40 cases) received no specific medicine. Positive rate of various peripheral
      lymphocyte subsets, including CD3, CD4, CD8, CD16, CD19 and CD25, in both groups
      was observed immediately after chemotherapy (T(0)) and 3 months later (T(1)), the
      same indexes of 20 healthy volunteers allocated in Group C were also determined
      at T(0) for control. RESULTS: The positive rates of CD4, CD4/CD8, CD16, CD19 and
      CD25 were significantly lower (P < 0.05) while that of CD8 was significantly
      higher (P < 0.05) in Group A and B at T(0) than those in Group C; at T(1), these
      indexes, except CD25, got significantly restored in Group A with the level
      approaching normal range (P > 0.05), and showed significant difference from those
      in Group B (P < 0.05), since these indexes in that group remained unchanged at
      the corresponding period. As for CD25, it was insignificantly changed in Group A
      after WYD treatment, and thus, at T(1), it was still lower than that in Group C
      (P < 0.05) and showed insignificant difference as compared with that in Group B
      (P > 0.05). Comparison of CD3 among the 3 groups showed no significant difference
      (P > 0.05). CONCLUSION: WYD could activate the immune function of NSCLC patients,
      and so it is recommended to be used in the treatment of NSCLC in clinical
      practice.

PMID- 16800991
TI  - Clinical study on therapy of clearing hallow viscera in treating critical
      patients with gastro-enteric function disorder.
AB  - OBJECTIVE: To explore the clinical effect of therapy of clearing hallow viscera
      in treating critical patients with gastro-enteric function disorder (GEFD).
      METHODS: Retrospective analysis was carried out on 96 critical patients. They
      were 48 patients in the treated group treated with Dachengqi Decoction and 48
      patients in the control group treated with Western medicine for promoting gastric
      dynamic force. The recovery rate, recovery time of gastro-enteric function,
      incidence rate and fatality rate of multiple organ dysfunction syndrome (MODS),
      as well as the level of plasma endotoxin (ET) before and after treatment between
      the two groups were compared. RESULTS: Comparison between the two groups in
      gastro-enteric function recovery rate (81.3% vs 45.8%), functional disorder
      sustaining time in patients who got recovered (1.2 +/- 0.3 days vs 4.0 +/- 1.1
      days), incidence rate (29.17% vs 52.08%) and fatality rate (28.57% vs 56.00%) of
      MODS all showed significant difference (P < 0.05 or P < 0.01). The plasma level
      of ET after treatment in the treated group was significantly lower than that in
      the control group (P < 0.05). CONCLUSION: Therapy of clearing hallow viscera has
      a good effect in treating critical patients with gastro-enteric function
      disorder, and could reduce the incidence and fatality of MODS.

PMID- 16800992
TI  - Growth inhibition and apoptosis inducing mechanisms of curcumin on human ovarian
      cancer cell line A2780.
AB  - OBJECTIVE: To explore the growth inhibition effects and apoptosis inducing
      mechanisms of curcumin on human ovarian cancer cell line A2780. METHODS: After
      treatment with 10 - 50 micromol/L curcumin for 6 - 24 h, the growth activity of
      A2780 cancer cells were studied by [4, 5-dimethylthiazol-2-yl]-2, 5
      diphenyltetrazolium bromide (MTT) colorimetry. Cellular apoptosis was inspected
      by flow cytometery and acridine orange-ethidium bromide fluorescent staining
      methods. The fragmentation of cellular chromosome DNA was detected by DNA ladder,
      the ultrastructural change was observed under a transmission electron microscope,
      and the protein levels of nuclear factor-kappa B (NF-kappaB, P65) and cysteinyl
      aspartate specific protease-3 (Caspase-3) in ovarian cancer cells were measured
      by immunohistochemistry. RESULTS: After treatment with various concentrations of
      curcumin, the growth inhibition rates of cancer cells reached 62.05% - 89.24%,
      with sub-G(1) peaks appearing on histogram. Part of the cancer cells showed
      characteristic morphological changes of apoptosis under fluorescence and electron
      microscopes, and the rate of apoptosis was 21.5% - 33.5%. The protein expression
      of NF-kappaB was decreased, while that of Caspase-3 was increased in a time
      dependent manner. CONCLUSION: Curcumin could significantly inhibit the growth of
      human ovarian cancer cells; inducing apoptosis through up-regulating Caspase-3
      and down-regulating gene expression of NF-kappaB is probably one of its molecular
      mechanisms.

PMID- 16800993
TI  - Effect of Gengnianchun Recipe on bone mineral density, bone biomechanical
      parameters and serum lipid level in ovariectomized rats.
AB  - OBJECTIVE: To observe the effect of Gengnianchun Recipe (GNC) on bone mineral
      density (BMD), bone biomechanical parameters and serum lipid level in the
      bilaterally ovariectomized (OVX) rats and to explore the prophylactic and
      therapeutic action of GNC on ovariectomy induced osteoporosis and hyperlipidemia.
      METHODS: OVX SD rats, 10 - 12 months old, were divided into different groups and
      fed with GNC 2 g/d, GNC 1 g/d and Nilestriol 0.125 mg/week, respectively for 4
      months to observe the change of BMD and bone biomechanical parameters of the
      lumbar vertebrae, and the serum levels of total cholesterol (TC), triglyceride
      (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein
      cholesterol (LDL-C), and to compare the effect of the two drugs on the morphology
      of the uterus. RESULTS: There was marked reduction in BMD and biomechanical
      parameters in lumbar vertebrae (P < 0.01) and increase of serum TC and LDL-C
      levels (P < 0.01) in rats after OVX. GNC or Nilestriol significantly improved the
      decreased BMD and biomechanical parameters of the lumbar vertebrae (P < 0.05 or P
      < 0.01), and reduced the serum TC and LDL-C levels (P < 0.01). In the Nilestriol
      group, the wet weight of uterus got increased obviously (P < 0.01), the number of
      uterine glands increased, uterine columnar epithelium thickened, and the mitotic
      figures in the epithelial stroma and myointimal cells augmented. But no such
      effect in wet weight and morphology of uterus was found in the GNC group.
      CONCLUSION: GNC could increase the BMD and biomechanical parameters of the lumbar
      vertebrae, reduce the serum TC and LDL-C levels, yet produce no adverse reaction
      in stimulating proliferation and hypertrophy of uterus.

PMID- 16800994
TI  - Effects of Yizhi Capsule on learning and memory disorder and beta-amyloid peptide
      induced neurotoxicity in rats.
AB  - OBJECTIVE: To explore the effects of Yizhi Capsule (YZC) on learning and memory
      disorder and beta-amyloid peptide induced neurotoxicity in rats. METHODS: Various
      doses of YZC were administered to Sprague-Dawley (SD) rats for 8 consecutive
      days, twice a day. On the 8th day of the experiment, scopolamine hydrobromide was
      intraperitoneally injected to every rat and Morris water maze test and shuttle
      dark avoidance test were carried out respectively to explore the changes of
      learning and memory capacities in the rats. Besides, after the cerebral cortical
      neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days,
      drug serum containing YZC was added to the cultured neurons before or after beta
      amyloid peptide(25 - 35) (Abeta(25 - 35)) intoxication to observe the protective
      effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in
      the supernatant. RESULTS: Compared with those untreated with YZC, the rats having
      received YZC treatment got superiority in shorter time of platform seeking in
      Morris water maze test, as well as elongated latent period and less times of
      error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum
      could effectively increase the survival rate of Abeta(25 - 35) intoxicated
      neurons and reduce the LDH contents in cultured supernatant. CONCLUSION: YZC has
      an action of improving learning and memory disorder, and good protective effect
      on Abeta(25 - 35) induced neurotoxicity in SD rats.

PMID- 16800996
TI  - Effect of electro-acupuncture in treating patients with lingual hemangioma.
AB  - OBJECTIVE: To explore the clinical effect of electro-acupuncture (EA) in treating
      patients with lingual hemangioma (LHG). METHODS: EA therapy was applied on 36
      patients by directly inserting the platinum needles into LHG through a trocar
      with plastic insulating cannula to protect the normal tissues and connecting the
      needles with the electro-chemical therapeutic apparatus of model ZAY-B. Then
      electricity was given until the tumor body got contracted and rigid. The result
      was assessed 6 months after EA was started. RESULTS: All patients were treated
      effectively, namely, the effective rate was 100%, with the therapeutic effect
      reaching grade I in 29 patients (80.6%), grade II in 7 (19.4%), and all having
      the function of tongue recovered to normal. CONCLUSION: EA shows special
      superiorities in treating LHG, proved to bring about less injury and quick
      recovery and being simple in operation. Especially when applied on huge LHG, it
      could not only remove the tumor, but also preserve the function of the tongue, so
      it is a brand-new approach that is likely to be accepted by patients.

PMID- 16800995
TI  - Clinical observation on treatment of chronic aplastic anemia by Shengxuening and
      cyclosporin A.
AB  - OBJECTIVE: To explore the therapy to further elevate the efficacy of the
      treatment of chronic aplastic anemia (CAA). METHODS: Forty-five patients with CCA
      were assigned into two groups, the 26 patients in the treated group were treated
      by Shengxuening (a Chinese herbal preparation) and cyclosporin A (CsA), and the
      19 patients in the control group were treated with androgen alone, with the
      therapeutic course lasting for over 3 months. Changes of peripheral blood
      picture, and the colony productivity of burst forming unit-erythroid (BFU-E),
      colony forming unit-erythroid (CFU-E) and colony forming unit-granulocyte
      macrophage (CFU-GM) in bone marrow were observed before and after 3 months
      treatment. The amount of erythrocyte and platelet infusion, frequency of
      infection, condition of hemorrhage and relevant death were also observed. The
      follow-up study was conducted for over half a year. RESULTS: The total effective
      rate in the treated group was 84.6%, which was significantly higher than that in
      the control group (52.6%, P < 0.05). Levels of hemoglobin, reticulocyte,
      neutrophil and platelet increased after treatment in the treated group, as
      compared with those before treatment, with significant difference (P < 0.05), and
      the colony productivity of BFU-E, CFU-E and CFU-GM in bone marrow also got
      significantly increased (P < 0.01), and showed significant difference from those
      in the control group (P < 0.05). CONCLUSION: Shengxuening-assisting CsA therapy
      is an effective measure for treatment of CAA.

PMID- 16800997
TI  - ZHANG Ting-dong - a pioneer in treating leukemia with arsenous acid.

PMID- 16800999
TI  - A survey on treatment of dry eye by traditional chinese medicine and integrative
      chinese and Western medicine.
AB  - Dry eye is now one of the most common superficial disorders in ophthalmology at
      home and abroad, and more and more people attach importance to the study. The
      ideal approach for treatment of dry eye is to normalize the condition by
      rebuilding the superficial circumstance of the eye, and to make tear film work as
      well as possible so as to relieve the irritating symptoms in the eye. The authors
      are making a comprehensive discussion on the methods and curative effects of
      treating dry eye by traditional Chinese medicine and by integrative Chinese and
      Western medicine in recent years, so as to introduce the distinctive features of
      the traditional Chinese medicine and integrative Chinese and Western medicine in
      this field.

PMID- 16801001
TI  - [Diagnostic value of fecal calprotectin in predicting an abnormal colonoscopy].
AB  - BACKGROUND AND OBJECTIVE: Abdominal pain and diarrhoea are common symptoms in the
      general population. The colonoscopy is the gold standard method of detecting an
      organic pathology in the colon. However, it is invasive; it can not be repeated
      frecuently; it is expensive; and the system is overloaded. Fecal calprotectin
      (FCP) is a marker that may detect organic pathologies of the colon. The aims of
      this study were to analyze the usefulness of FCP to predict an abnormal
      colonoscopy and to correlate the levels of FCP with the degree of activity in
      inflammatory bowel disease (IBD). PATIENTS AND METHOD: 190 people were included
      in the study. All of them underwent a colonoscopy and a stool sample. People were
      divided in: normal colonoscopy: 117 people, and 28 colon adenomas, 20 colorectal
      cancer (CRC) and 25 IBD. RESULTS: The mean (SD) FCP concentration was 2,171.1
      (2,133.6) mg/kgin patients with IBD and 726.6 mg/kg (533) in CRC. Both results
      were significantly elevated compared with those of healthy controls [114 (113)]
      mg/kg In patients with IBD, their levels correlated directly with the activity of
      the inflammation. 217 mg/kg was the best cut-off for discriminating patients with
      organic colon disorders. The sensibility was 85% and NPV was 93%. NSAIDs use was
      a clinical variable which was connected with a high FCP concentration in patients
      with normal colonoscopy. CONCLUSIONS: The higher levels of FCP were found in
      people with IBD and CRC. The measurement of FCP is a non-invasive, inexpensive,
      reliable and easily measured test. Among people with abdominal pain and
      diarrhoea, testing for FCP allows us to select those who must undergo a
      colonoscopy. NSAIDs can raise the levels of FCP in people with normal
      colonoscopies.

PMID- 16801002
TI  - [Clinical and pharmacokinetic interactions between methadone and nelfinavir
      (Nemesia study)].
AB  - BACKGROUND AND OBJECTIVE: Patients on methadone maintenance therapy who are
      administered nelfinavir show a decrease in methadone plasma levels. However, the
      clinical relevance of this fact is seldom significant because it does not
      correlate with the appearance of opioid withdrawal symptoms (OWS). The objective
      of this study was to assess the clinical and pharmacokinetic interactions between
      methadone and nelfinavir. PATIENTS AND METHOD: A prospective multicenter study of
      human immunodeficiency virus (HIV) positive patients on stable methadone therapy
      who initiated nelfinavir was performed. To determine the presence of OWS, 2
      questionnaires, objective and subjective, were administered at weeks 1, 2, 3 and
      4. A pharmacokinetic study measuring the minimal plasmatic concentration of
      methadone was done at baseline and at week 4. RESULTS: 29 patient were included.
      In 7 patients who underwent pharmacokinetic studies, the minimal plasmatic
      concentration of methadone decreased after 4 weeks of nelfinavir treatment from
      6.889 ng/ml to 4.354 ng/ml (37%; p = 0.046). However the results of the
      questionnaires did not show the significant OWS, which precluded an increase in
      the dose of methadone. CONCLUSIONS: In patients under stable methadone treatment,
      antiretroviral therapy including nelfinavir does not require any significant
      modification of methadone dose. The decrease in methadone plasmatic levels does
      not correlate with OWS.

PMID- 16801003
TI  - [Continuous glucose monitoring in high-risk subjects for developing type 2
      diabetes].
AB  - BACKGROUND AND OBJECTIVE: To assess the relevance of unrecognised hyperglycaemia
      among high-risk subjects for developing type 2 diabetes. SUBJECTS AND METHOD:
      Cross-sectional multicentre study in primary care. Subjects aged 40 to 75 years
      with previous evidence of impaired glucose metabolism were screened according to
      the World Health Organization rules by means of an oral glucose tolerance test
      (OGTT). Those with diabetes diagnostic criteria were excluded. An individualized
      48-h ambulatory continuous glucose monitoring (CGM) calibrated by plasma values
      (Glucoday) was performed. Data from biosensor activity were computerized in order
      to identify hyperglycaemic records. RESULTS: 50 out of 64 screened subjects were
      included and evaluated; there were 30 female (60%). Mean age was 59 years; body
      mass index, 30.9; HbA1c, 5.3%, and HOMA, 2.8. Regarding the CGM results, 9 whole
      registers (18%) were rejected because of technical problems and 41 continuous
      profiles (72%) were analysed, corresponding to 17 (41.5%) subjects with normal
      OGTT and 24 (58.5%) with non-diabetic hyperglycaemia on OGTT. Mean CGM time with
      hyperglycaemia (fasting > or = 6.1 mmol/l or non-fasting > or = 7.8 mmol/l)
      accounted for 5.8 h, a 17.2% of the effective register per subject (33.8 h). Both
      groups matched the World Health Organization diabetes diagnostic interval
      (fasting > or = 7 mmol/l or non-fasting > or = 11.1 mmol/l): 1.1 h of effective
      register (3.6%) and 1.2 h (3.3%), respectively. CONCLUSIONS: The CGM evidenced a
      high degree of unrecognised hyperglycaemia among high-risk individuals.
      Therefore, casual plasma glucose measurements should be recommended to achieve
      early screening.

PMID- 16801004
TI  - [Hereditary hyperferritinemia and iron overload: they are not synonymous].

PMID- 16801005
TI  - [Should patients included in clinical trials be paid?].

PMID- 16801006
TI  - [Pharmacological treatment of bleeding peptic ulcer].

PMID- 16801007
TI  - [More on therapeutic options in fibromyalgia].

PMID- 16801008
TI  - [Calculation of risks of passive smoking].

PMID- 16801010
TI  - [Alternatives to the excess of premature hospital mortality in weekends].

PMID- 16801011
TI  - [Effectiveness of vaccination in high risk population].

PMID- 16801012
TI  - [Histiocytic sarcoma].

PMID- 16801013
TI  - [Thyroid cancer detection by PET].

PMID- 16801014
TI  - [Neuroleptic malignant-like syndrome following abrupt withdrawal of baclofen].

PMID- 16801015
TI  - [Genetic predisposition in cutaneous melanoma].
AB  - The incidence of cutaneous melanoma has increased worldwide in the last 20 years.
      Research on potential risk factors, both environmental and genetic, has led us to
      some new and interesting conclusions. Ultraviolet radiation is clearly the main
      environmental risk factor for melanoma, but its relationship is complex and
      controversial. With regard to genetic factors, the discovery of two types of
      genes was a great advance in further understanding the biology of the melanocyte.
      CDKN2A (p16) is the prototype of the high-penetrance, low-prevalence gene related
      to melanoma. This gene has been studied in some families in which several members
      have been diagnosed with melanoma. In the general population with non-familial
      melanoma, low-penetrance, high-prevalence genes such as MC1R seem to be more
      interesting. Studies on the MC1R gene have not only shown its importance in skin
      and hair pigmentation, but also in the development of melanoma. Functional
      studies on CDKN2A and MC1R have led us to new and important conclusions. The
      analysis of data from studies on families, twins and control cases, with the
      collaboration of several countries, will lead us to new discoveries. For the
      primary and secondary prevention of this tumor, we must promote public health
      campaigns on the dangers of sun exposure and the identification of individuals at
      high risk.

PMID- 16801016
TI  - [Study of variables associated with skin cancer in Chile using principal
      component analysis].
AB  - BACKGROUND: The incidence of skin cancer in Chile has increased in recent years.
      OBJECTIVE: To associate variables with skin cancer in Chile through indices
      generated using multivariate descriptive statistical techniques. MATERIAL AND
      METHOD: During May 2004, information was gathered from demographic,
      meteorological and clinical data from Chile corresponding to fiscal year 2001,
      the latest complete, official information available for the country's Health
      Services as a whole. The variables developed by the following were studied: the
      National Statistics Institute (INE), the Ministry of Health (MINSAL), the
      Ministry of Planning and Cooperation (MIDEPLAN), the National Health Fund
      (FONASA), the Chilean Meteorological Directorate, Federico Santa Maria Technical
      University and the Directorate-General for Water. A Principal Component Analysis
      (PCA) was then performed on the data obtained. RESULTS: The first three principal
      components were selected, with a cumulative explained variance percentage of
      54.48 %. The first principal component explains 24.92 % of the variance, and is
      related to climatic and geographic variables. The second principal component
      explains 15.77 % of the variance, and is mainly related to FONASA's beneficiary
      population and the poverty rate. The mortality rate from skin cancer runs
      significantly against this component. The third principal component explains
      13.79 % of the variance, and is related to population characteristics, such as
      total catchment population, female population and urban population. CONCLUSION:
      Performing PCA is useful in studying the factors associated with skin cancer.

PMID- 16801017
TI  - [Prognosis for cutaneous melanoma according to surgical department: comparative
      study at a tertiary care hospital].
AB  - INTRODUCTION: Surgical treatment of melanoma is performed by dermatologists and
      general or plastic surgeons. It is not known whether the type of specialist
      treating the melanoma results in a different prognosis for these patients.
      MATERIAL AND METHODS: A retrospective study was carried out on the
      epidemiological, clinical/histological and evolutional characteristics of all
      patients diagnosed with melanoma at Hospital Gregorio Maranon over a 10-year
      period (1994-2003). The differences by hospital department where the patients
      were treated (dermatology, general surgery and plastic surgery) were noted.
      RESULTS: Over 90 % of the patients with melanoma were treated by the Dermatology
      Department. The thickness of the tumors and the presence of histologic ulceration
      were significantly higher in the melanomas treated by general and plastic
      surgeons (p <0.05). The differences in overall average survival (105, 55 and 77
      months) and disease-free time (88, 24 and 51.3 months) in the melanomas operated
      on by dermatologists, general surgeons and plastic surgeons, respectively, were
      significant (p <0.001). CONCLUSIONS: This study confirms that there are
      significant differences in the clinical and histological characteristics and the
      life prognosis of patients with cutaneous melanoma treated by different
      specialists. The melanomas treated by general or plastic surgeons have usually
      been developing for a longer time, and therefore are thicker and more often
      ulcerated than those treated by dermatologists, resulting in a lower survival
      period. With appropriate medical and surgical training, dermatologists are the
      most suitable specialists for early diagnosis and treatment.

PMID- 16801018
TI  - [Blastic NK-cell lymphoma].
AB  - Blastic NK (<<natural killer>>) cell lymphoma is a rare type of lymphoma,
      recognized as an independent entity in the new World Health Organization-European
      Organization for Research and Treatment of Cancer (WHO-EORTC) classification for
      cutaneous lymphomas. Its clinical, morphological and immunophenotypical
      characteristics are relatively well defined. It frequently starts with extranodal
      involvement (primarily cutaneous), often presents with splenomegaly and
      pancytopenia, and initially responds well to chemotherapy, although the medium
      term prognosis is usually poor. It was first considered to originate from
      immature NK lymphocytes, but now its origin is thought to be plasmacytoid
      dendritic cell precursors. We present the clinicopathological characteristics of
      a new case of this entity in a 78-year-old male patient.

PMID- 16801019
TI  - [Pseudovascular squamous cell carcinoma].
AB  - The adenoid form of squamous cell carcinoma is a neoplasm that is characterized
      by the fact that it presents a pseudoglandular pattern in the histological study.
      The biological phenomenon that explains this histological pattern is
      acantholysis; when the latter is massive, the tumor may even mimic a vascular
      proliferation, and is known as pseudovascular squamous cell carcinoma. This tumor
      has the clinical characteristics of a squamous cell carcinoma, but
      histologically, it may mimic an angiosarcoma. Most cases of pseudovascular
      squamous cell carcinoma of the skin have a poor prognosis.

PMID- 16801020
TI  - [Desmoplastic trichoepithelioma: presentation of two cases].
AB  - Trichoepithelioma is a benign neoformation with hair follicle differentiation
      that may clinically present in solitary, multiple or desmoplastic form. From a
      histopathological standpoint, it poses some diagnostic difficulties with basal
      cell carcinoma. We present two cases of desmoplastic trichoepithelioma, a rare
      adnexal tumor whose incidence is estimated at 2 per 10,000. Desmoplastic
      trichoepithelioma is a benign lesion, clinically and histologically similar to
      other dermatoses, and presents a true diagnostic challenge.

PMID- 16801021
TI  - [Merkel cell carcinoma in a patient with chronic lymphocytic leukemia].
AB  - Merkel cell carcinoma (MCC) is an infrequent neuroendocrine tumor of the skin
      with a high potential for local recurrence, lymphatic dissemination and distant
      dissemination. We present a case of MCC in a male patient with chronic
      lymphocytic leukemia (CLL). The immunosuppression induced by the leukemia or by
      the chemotherapy could play a pathogenic role in the association of these
      diseases. Positron emission tomography (PET) was a useful staging technique in
      this patient, and made the differential diagnosis of the lymph node involvement
      from MMC and CLL possible.

PMID- 16801022
TI  - [Spindle-cell carcinoma in situ treated with 5% imiquimod].
AB  - We present the case of a 70-year-old woman with no personal history of interest
      who presented to her physician with a plaque in the right infraumbilical region
      whose largest diameter measured nine centimeters. The clinical and histological
      diagnosis was Bowen's disease. She was treated with 5 % imiquimod cream, once a
      day, four times a week, for eight weeks, with an excellent response. One year
      after treatment, no new lesions have appeared in the treated area.

PMID- 16801023
TI  - [Cutaneous leukocytoclastic vasculitis and renal carcinoma].
AB  - The association between leukocytoclastic vasculitis and solid tumors like renal
      carcinoma has been infrequently described. We present the case of a 76-year-old
      woman who began with skin lesions on the legs that were clinically and
      histologically diagnosed as leukocytoclastic vasculitis. During analysis of the
      symptoms, she was diagnosed with renal carcinoma. After the tumor was excised,
      the vasculitis lesions disappeared, with no recurrence during the follow-up
      period.

PMID- 16801024
TI  - [Aquagenic syringeal acrokeratoderma. Presentation of two cases].
AB  - Aquagenic syringeal acrokeratoderma is an infrequently described acquired,
      transitory keratoderma that is exacerbated when the palms and/or soles are
      immersed in water. It manifests as whitish or yellowish flattened, translucent
      papules and plaques, located in areas of pressure or trauma on the palms and/or
      soles. Involvement is usually bilateral. The histologic features are non
      specific, showing a slight dilation of the intraepidermal portion of the eccrine
      sweat duct. The process tends to remit spontaneously. We present the case of two
      women, aged 20 and 21.

PMID- 16801025
TI  - [Skin infection with Fusarium in an immunocompetent patient].
AB  - Fusarium spp. are fungi found throughout the world and can cause a great variety
      of skin infections, mainly in immunodepressed individuals. We present a case of
      skin infection with Fusarium sp. which manifested as painful superficial ulcers
      on the legs of an immunocompetent female patient, who had applied <<medicinal
      mud>> as a <<natural remedy>> for leg pain. The condition was cured with oral
      itraconazole and local treatments.

PMID- 16801027
TI  - [Bleeding perianal tumor].

PMID- 16801026
TI  - [Pruritic papules in the axillae].

PMID- 16801028
TI  - [Scleredema].

PMID- 16801029
TI  - [Recurrent varicella in a woman with mantle cell lymphoma].

PMID- 16801030
TI  - [Complications of varicella for which dermatologists are rarely consulted,
      another argument in favor of systematic immunization].

PMID- 16801031
TI  - Hematological and biochemical factors predicting SARS fatality in Taiwan.
AB  - BACKGROUND/PURPOSE: Severe acute respiratory syndrome (SARS) has a high fatality
      rate worldwide. We examined the epidemiologic and clinical factors associated
      with death for all laboratory-confirmed SARS patients in Taiwan. METHODS: Using
      initial data in medical records reported by hospitals to the Center for Disease
      Control in Taiwan, we analyzed whether hematological, biochemical and arterial
      blood gas measures could predict fatality in 346 SARS patients. RESULTS: Both
      fatalities (n = 73; 21.1%) and survivors had elevated plasma concentration of
      initial C-reactive protein (CRP), but the mean CRP concentration was higher in
      fatalities (47.7 +/- 43.3 mg/L) than in survivors (24.6 +/- 28.2 mg/L). Initial
      lymphocyte counts were low in both fatalities (814 +/- 378/microL) and survivors
      (1019 +/- 480/microL). After controlling for age and sex, multiple logistic
      regression analysis showed that hematological factors significantly associated
      with fatality included initial neutrophil count > 7000/microL (odds ratio [OR] =
      6.4), initial CRP concentration > 47.5 mg/L (OR = 5.8) and lactic acid
      dehydrogenase (LDH) > 593.5 IU/L (OR = 4.2). Factors significantly associated
      with initial CRP concentration > 47.5 mg/L included dyspnea (OR = 4.3), red blood
      cell count < 4.1 x 106/microL (OR = 4.3) and serum aspartate aminotransferase >
      57 IU/L (OR = 3.1). CONCLUSION: Initial neutrophil count, CRP and LDH levels are
      important predictors of mortality from SARS.

PMID- 16801032
TI  - Outcome of primary percutaneous coronary intervention in octogenarians with acute
      myocardial infarction.
AB  - BACKGROUND/PURPOSE: Acute myocardial infarction (AMI) results in more
      complications and increased mortality in octogenarians compared to patients in
      younger age groups. This study investigated the short- and long-term outcomes in
      octogenarians after primary percutaneous coronary intervention (PCI). METHODS:
      During the study period from May 1997 to August 2004, 54 patients > or = 80 years
      old with ST-elevation myocardial infarction (STEMI) were eligible for primary
      PCI. Data collected included baseline clinical characteristics and usage of
      cardiovascular medications. Diagnostic coronary angiography and revascularization
      procedures were performed using standard practices. During hospitalization, the
      clinical course including serial changes in cardiac enzymes, adverse events
      associated with myocardial infarction or treatment, and inhospital or long-term
      mortality of patients were recorded. RESULTS: The mean age of the 54 patients (35
      men, 19 women) was 82.8 +/- 2.5 years (range, 80-89 years). Among them, 27 (50%)
      had anterior infarction, six (11%) had anterolateral infarction, and 21 (39%) had
      inferior infarction, inclusive of three patients with accompanying right
      ventricular infarction. Among them, 20 (37%) patients were in Killip class I,
      nine (17%) were in class II, two (4%) in class III, and 23 (43%) in class IV. The
      mean delay from onset of symptoms to arrival in hospital was 220 +/- 167 minutes,
      and 189 +/- 169 minutes from hospital arrival to reperfusion. Diagnostic coronary
      angiography revealed that 48 (89%) patients had multivessel disease. Inhospital
      death occurred in 23 (43%) patients, with the leading causes of death being
      profound cardiogenic shock (61%), and free wall rupture (26%). CONCLUSION:
      Octogenarian patients who developed STEMI tended to have multivessel disease.
      These patients had a high inhospital mortality rate that was most likely to be
      due to cardiogenic shock.

PMID- 16801033
TI  - Six-month nocturnal nasal positive pressure ventilation improves respiratory
      muscle capacity and exercise endurance in patients with chronic hypercapnic
      respiratory failure.
AB  - BACKGROUND/PURPOSE: This study was designed to investigate the effects of 6
      months of nocturnal nasal positive pressure ventilation (NNPPV) on respiratory
      muscle function and exercise capacity in patients with chronic respiratory
      failure. METHODS: A prospective, randomized, controlled design was used. Twenty
      nine patients with chronic respiratory failure were enrolled and allocated to
      either the NNPPV (n = 14) or control group (n = 15). Patients in the NNPPV group
      received bi-level positive pressure ventilation via nasal mask for 6 consecutive
      months. Arterial blood gas, respiratory muscle assessment and 6-minute walk test
      (6MWT) were performed before and after the 6-month NNPPV intervention.
      Respiratory muscle function was assessed using the variables of maximal
      inspiratory pressure (Pimax), maximal expiratory pressure (Pemax), and maximum
      voluntary ventilation (MVV). RESULTS: Subjects in the NNPPV group showed a
      significant improvement in blood gas exchange and increased 6-minute walk
      distance (6MWD) compared to baseline and the control group. The 6MWD was
      significantly increased from 257.1 +/- 114.1 to 345.2 +/- 109.9 m (34.3%) in the
      NNPPV group. NNPPV also significantly improved MVV and Pimax relative to
      baseline. MVV was significantly increased from 19.2 +/- 6.5 to 22.3 +/- 7.1 L/min
      (16.1%) in the NNPPV group (p < 0.05). Furthermore, there was a significant
      correlation between the magnitude of MVV improvement and 6MWD change. CONCLUSION:
      The 6-month NNPPV treatment significantly decreased the partial pressure of
      carbon dioxide and improved daytime respiratory muscle function, thus
      contributing to exercise-capacity increase in patients with chronic respiratory
      failure.

PMID- 16801034
TI  - Kinematic navigation in total knee replacement--experience from the first 50
      cases.
AB  - BACKGROUND/PURPOSE: Proper alignment of the prosthesis is critical in total knee
      replacement (TKR) to minimize long-term wear, risk of osteolysis, and loosening
      of the prosthesis. This study examined the accuracy of lower limb alignment
      obtained using a kinematic navigation system for TKR, and the extra time needed
      to adopt this system. METHODS: From August 2002 to April 2003, 71 patients with
      knee osteoarthritis underwent 79 primary TKR operations by the same surgical
      team. Fifty of these operations were performed with the aid of the CT-free
      kinematic navigation system, and the remaining 29 were performed with
      conventional manual methods. Results, including operation time, radiographic
      alignment of the prosthesis and complications, for the two groups were compared.
      RESULTS: Patients in the kinematic navigation group achieved better accuracy in
      the coronal plane than the conventional group in terms of postoperative
      mechanical axis (1.89 +/- 0.63 degrees vs. 3.38 +/- 1.07 degrees ). Less
      variation was noted in the navigation group (femur: SD 1.88 degrees vs. 7.12
      degrees ; tibia: SD 1.54 degrees vs. 2.99 degrees ), although the difference in
      the mean values was not significant (p = 0.475 and 0.55, respectively). The
      operation time (from skin to skin) in the navigation group (100.6 +/- 4.3
      minutes) was longer than that in the conventional group (92.7 +/- 5.1 minutes; p
      = 0.027). Two perioperative fractures occurred in the navigation group, both of
      which were attributed to patient factors as opposed to operation procedures. No
      major complications such as infection or pulmonary embolism occurred during this
      study. CONCLUSION: Use of a kinematic navigation system in TKR provides better
      accuracy than conventional manual methods. The technique is easy to use, has a
      short learning curve, and requires an additional operation time of less than 10
      minutes. Precise alignment can be achieved with the aid of navigation in most
      cases.

PMID- 16801035
TI  - Clinical features of Ehlers-Danlos syndrome.
AB  - BACKGROUND/PURPOSE: Ehlers-Danlos syndrome (EDS) is a clinically and genetically
      heterogeneous connective tissue disorder characterized by hyperextensibility of
      the skin, hypermobility of joints, and tissue fragility. This retrospective study
      analyzed the characteristics of patients with EDS. METHODS: Review of medical
      records identified 16 cases of EDS during the study period from November 1997 to
      October 2002. Data on these patients, including clinical presentation, physical
      examinations, Beighton score, echocardiogram, bone mineral density findings and
      clinical classification, were analyzed. RESULTS: The age of the patients ranged
      from 13 months to 36 years. All patients had skin hyperextensibility, joint
      hypermobility (Beighton score > 5 points), and tissue fragility. Complete bone
      mineral density study was performed in 11 patients and revealed that all had
      osteoporosis. Echocardiographic study was performed in 14 patients and showed
      aortic root dilatation/valve prolapse in 6/14 (43%). Other common features of EDS
      had the following prevalence: premature rupture of membranes in 3/16 (19%);
      prematurity in 3/16 (19%); neonatal hypotonia in 5/16 (31%); congenital hip
      dislocation in 3/16 (19%); unstable gait in 7/16 (44%); bone fracture(s) in 3/16
      (19%); motor delay in 3/16 (19%); scoliosis in 3/16 (19%); short stature in 7/16
      (44%); and positive family history in 8/16 (50%). All patients had a Beighton
      score of more than 5 points. CONCLUSION: The results of this study emphasize the
      importance of echocardiographic monitoring of aortic size and valvular condition,
      and assessment of bone mineral density in patients with EDS. Clinical evaluation
      and counseling should be undertaken prior to pregnancy in patients with EDS
      because of the risk from labor and vaginal delivery in patients with type IV and
      the inability to distinguish EDS subtypes in Taiwan due to the unavailability of
      biochemical assay or molecular mutation analysis as part of standard care.

PMID- 16801036
TI  - Alcohol-related Injuries at an emergency department in Eastern Taiwan.
AB  - BACKGROUND/PURPOSE: Injuries are major causes of mortality and morbidity in
      Taiwan. Alcohol involvement often plays a role in injuries. The purpose of this
      study was to determine the prevalence of alcohol-related injuries at an emergency
      department in Eastern Taiwan and their associated factors. METHODS: All injured
      patients who made emergency visits between October 2002 and September 2003 were
      enrolled. For each patient, the attending nurse completed an injury-coding sheet,
      which included the results of an assessment of whether the patient had an alcohol
      odor or alcohol consumption related behavior. Nurses recorded suspicion of
      alcohol consumption based on possible categories of "no alcohol odor", "alcohol
      odor", "intoxicated", "suspected" or "unknown". Blood alcohol testing was also
      performed based on the decision of the attending physician. Injuries were defined
      as alcohol-related based on the report of "alcohol odor" or "intoxicated" by the
      nurse or a positive blood alcohol test. Logistic regression was used to assess
      the significance of the association of possible related factors with alcohol
      related injury. RESULTS: A total of 8822 eligible visits were studied and 14%
      were classified as alcohol-related. The proportion of alcohol-related injuries
      was 14.9% for vehicle-related injuries, and 51.3% for assaults. Male, young to
      middle aged, aboriginal ethnicity and visits after midnight were factors
      associated with increased likelihood of alcohol-related injuries. Multiple
      logistic regression analysis revealed that the three factors most significantly
      associated with alcohol-related injuries were visits after midnight (odds ratio,
      OR, 7.5; 95% confidence interval, CI, 6.4-8.9], assaults (OR, 3.4; 95% CI, 2.3
      4.8), and head injuries (OR, 2.7; 95% CI, 2.3-3.2). CONCLUSION: Injuries were
      alcohol related in one out of seven patients this study from an emergency
      department in eastern Taiwan. Ongoing epidemiologic monitoring of the prevalence
      and nature of alcohol abuse among patients visiting the ED are urgently needed.

PMID- 16801037
TI  - Factors influencing medical students' choice of specialty.
AB  - BACKGROUND/PURPOSE: Medical school graduates are the source of a country's
      physicians. Determining how the graduates of these schools select their areas of
      specialization is the key to achieving a balanced distribution of doctors among
      all specialties. The purposes of this study were to determine the factors that
      influence medical students' choice of medical specialty, and to derive the
      relative weight of each factor. METHODS: We constructed a two-tiered analytic
      hierarchy process (AHP) model which was represented in a questionnaire sent to
      500 senior medical students to survey their opinions. The relative weight of each
      factor in the model was calculated. Analysis of variance and t test were applied
      to test for any significant differences in opinion among the students. RESULTS:
      On the first tier of the AHP model, the aspect of "personal preferences and work
      achievement" had the highest weight of 0.460, followed by "specialty
      characteristics" with 0.291, and then the "specialty training process" with
      0.249. Of the 14 criteria on the second tier, "personal intelligence/ability
      preference" had the highest weight of 0.197, followed by "career opportunities"
      with 0.107 and "lifestyle after completion of training" with 0.094. CONCLUSION:
      This study found that personal intelligence/ability preference and career
      opportunities were more important factors to the current generation of students
      in choosing a specialty. Knowledge of these students' attitudes could form the
      basis for the development of strategies to enhance the attractiveness of
      specialties facing the problem of a shortage of manpower.

PMID- 16801039
TI  - Paralysis periodica paramyotonica caused by SCN4A Arg1448Cys mutation.
AB  - Paralysis periodica paramyotonica is an overlapping disease that shares the
      features of paramyotonia characteristic of paramyotonia congenita (PC) and
      periodic paralysis characteristic of hyperkalemic periodic paralysis. We report
      the case of a 23-year-old man with paralysis periodica paramyotonica. His father
      and a younger brother also exhibited a similar phenotype. A SCN4A Arg1448Cys
      mutation was detected in this family. The affected family members exhibited
      marked shifts in compound muscle action potential amplitudes on exercise test,
      and muscle weakness could be induced by potassium loading and cold exposure. This
      case demonstrates that SCN4A Arg1448Cys can produce paralysis periodica
      paramyotonica. Other genetic or environmental factors may modulate the
      manifestation of SCN4A Arg1448Cys mutation.

PMID- 16801038
TI  - Retinoblastoma with spinal recurrence presenting as spinal cord compression.
AB  - Central nervous system (CNS) involvement is not rare in extraocular
      retinoblastoma, and it is not surprising to find it in view of its route of
      spread. However, although spinal recurrence presenting as spinal cord compression
      (SCC) is a form of CNS involvement, it is extremely rare. This report describes
      two patients with unilateral retinoblastoma with spinal recurrence presenting as
      SCC. The first patient developed erythematous swelling of the right foot and
      weakness of the bilateral lower limbs at 7 months after left enucleation.
      Examination revealed pitting edema of bilateral feet and muscle power of 2+ to
      3+, with intact sensory function. The second patient developed weakness of the
      bilateral lower limbs, and defecative and urinary difficulty for 2 days at 8
      months after left enucleation. Examination revealed pitting edema of bilateral
      feet and muscle power of 2+, with defective sensory function. Both patients
      received surgery and local irradiation after SCC. The first patient refused
      chemotherapy and survived only 4 months due to disease progression. The second
      patient received systemic and intrathecal chemotherapy, and survived 19.5 months
      without disease progression. Spinal recurrence with SCC should be suspected when
      leg weakness or bowel or bladder disturbance occurs in patients with
      retinoblastoma.

PMID- 16801040
TI  - Virtual bronchoscopy for diagnosis of recurrent respiratory papillomatosis.
AB  - Virtual bronchoscopy is a new method for viewing helical/spiral computed
      tomography (CT) images of the tracheobronchial trees. Using commercially
      available software to process the CT data, the tracheobronchial trees can be
      inspected through a series of three-dimensional images. Recently, this technique
      has been increasingly used to detect benign and malignant airway stenosis. We
      report the findings of virtual bronchoscopy in a 41-year-old man with recurrent
      respiratory papillomatosis (RRP). Several tiny nodules were evident in the lower
      trachea. Fiberoptic bronchoscopy was performed 1 month later during a planned
      surgery for laryngeal papillomas, and the findings were in agreement with virtual
      bronchoscopy. Detection of intrabronchial spreading in RRP is important since
      peripheral seeding of RRP can cause complications, including recurrent pneumonia,
      obstructive atelectasis, hemoptysis, and, rarely, may degenerate to squamous cell
      carcinoma. Virtual bronchoscopy is an alternative method for inspecting the
      tracheobronchial trees in patients with RRP when laryngeal papillomas impede
      fiberoptic bronchoscopy.

PMID- 16801041
TI  - Differential diagnosis of cystic lymphangioma of the pancreas based on imaging
      features.
AB  - Lymphangioma is a benign tumor, which is a consequence of lymphatic malformation
      with blockage of lymphatic flow. Most lymphangiomas occur in the neck and
      axillary region, and < 1% occur in the mesentery or retroperitoneum.
      Lymphangiomas arising from the pancreas are extremely rare. We report the case of
      a 34-year-old woman with cystic lymphangioma of the pancreas without major
      symptoms or signs. A 6 x 6 cm intra-abdominal cystic mass was incidentally
      revealed by sonography during a health examination. It is always a challenge to
      differentiate the lesion from other possible cystic-like pancreatic neoplasms.
      Differential diagnosis of cystic lymphangioma from other cystic-like tumors of
      the pancreas can be performed based on their imaging characteristics, including
      presence of septa, cystic or wall calcification, soft tissue, wall thickness,
      single or multiple loculation, and dilatation of the pancreatic duct. Post
      gadolinium magnetic resonance imaging is excellent in defining the origin of
      intra-abdominal cystic mass and intracystic septa.

PMID- 16801042
TI  - Treacher Collins syndrome with a de Novo 5-bp deletion in the TCOF1 gene.
AB  - Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial
      development with features including malar hypoplasia, micrognathia, microtia,
      downward slanting palpebral fissures, lower eyelid coloboma, conductive hearing
      loss, and cleft palate. TCS is caused by mutations in the TCOF1 gene, which
      encodes the nuclear phosphoprotein treacle. Here, we describe a 1-day-old male
      infant with classical TCS presentation. A 5-bp deletion in exon 22 of the TCOF1
      gene (3469del ACTCT) was found to cause a premature stop codon. This is the first
      report of TCOF1 gene mutation in the Taiwanese population.

PMID- 16801043
TI  - Treatment of pulp floor and stripping perforation by mineral trioxide aggregate.
AB  - Mineral trioxide aggregate (MTA) has been widely used to repair various kinds of
      tooth perforations, but its use for obturation of the entire root canal has not
      been reported. We report two cases of tooth perforation successfully repaired
      with MTA. The first patient was a 78-year-old male with calcified canal and pulp
      floor perforation in the left maxillary first premolar. After bypass of the
      calcified palatal canal, both buccal and palatal canals were filled with gutta
      percha, and the pulp floor perforation was repaired with MTA. Clinical success
      with no evident radicular lesion was found at the 18-month follow-up. The second
      patient was a 51-year-old female with a stripping perforation in a C-shaped root
      canal of the right mandibular second molar detected after removal of a post.
      Following root canal debridement and calcium hydroxide therapy to control
      inflammation at the stripping perforation site, apical and furcation bone healing
      were observed by radiographic examination. The stripping perforation was repaired
      by obturation of the entire C-shaped root canal with MTA. Observation at the 9
      month follow-up revealed bone healing without any clinical symptoms and signs.
      These cases suggest that MTA is an alternative root canal obturation material for
      treatment of stripping perforation in a C-shaped root canal and for repair of
      pulp floor perforation.

PMID- 16801045
TI  - Anterior tentorium-based epidermoid tumours: results of radical surgical
      treatment in 96 cases.
AB  - A retrospective analysis of 96 surgically treated tentorium and anterior
      tentorial hiatus-based epidermoid tumours from 1997 - 2004 is presented. The most
      prominent symptoms were headache (53.1%) and ataxia (44.8%). The average tumour
      size was 4.4 cm. Surgical approaches included posterior cranial fossa route (85
      cases), basal subtemporal middle fossa route (9 cases) and combined posterior
      fossa and subtemporal routes in two cases. Total tumour resection was performed
      in 46 patients. Eight and four patients developed transient and sustained
      postoperative neurological deficits respectively. There was mortality in two
      patients. There was non-symptomatic recurrence of the tumour in two cases. Ninety
      four patients are leading active functional lives. Radical and safe resection of
      anterior tentorium-based epidermoid tumours is associated with symptomatic relief
      and lasting cure. Extensive drilling of the petrous bone can be avoided. Gentle
      dissection of the tumour and capsule from the critical neurovascular structures
      can limit post-operative morbidity.

PMID- 16801044
TI  - Surgical management of tuberculum sellae meningioma: role of selective extradural
      anterior clinoidectomy.
AB  - A retrospective analysis of 32 patients with tuberculum sellae meningiomas who
      underwent surgery via a unilateral pterional approach was performed. A selective
      extradural anterior clinoidectomy (SEAC) technique was added in 20 patients. All
      patients had visual dysfunction preoperatively. Macroscopically complete removal
      with Simpson grade II was performed in 28 patients (87.5%). The postoperative
      visual function improved in 25 (78.1%), did not change in 3 (9.4%), and worsened
      in 4 patients (12.5%). The SEAC technique was effective, especially for removal
      of the tumour extending into the sellae/pituitary stalk (9 patients), the optic
      canal (4 patients) and hypothalamus (4 patients) with preservation of the visual
      and endocrinological function. These results were superior to those of surgery
      without SEAC technique. This technique is therefore recommended for complete
      resection of the tuberculum sellae meningiomas extending to the surrounding
      anatomical structures as the SEAC procedure reduces the risk of intraoperative
      optic nerve injury considerably.

PMID- 16801046
TI  - Surgical indications for arteriovenous malformations in patients over the age of
      60 years: retrospective analysis of 33 patients.
AB  - This retrospective study investigated the surgical indications in 33 patients
      aged > 60 years with brain arteriovenous malformation (AVM) taken from a group of
      294 cases between 1981 and 2004. These 33 patients were further classified to two
      age groups: 60 - 64 years (A group) and > or = 65 years (B group). The overall
      haemorrhagic rate at initial presentation was 46.6% in the 294 patients. The rate
      was 48.5% in patients aged > 60 years, and 72.2 and 20% in the A and B groups,
      respectively. In three of four cases with extremely poor outcome with modified
      Rankin Scale 5 and 6, the cause of poor outcome was haemorrhage in those aged >
      65 years. Because of the high haemorrhagic rate and poor outcome after
      haemorrhage, surgical treatment is indicated for patients aged > 60 years.

PMID- 16801047
TI  - In-vivo measurement of brain relaxation after lobectomies.
AB  - Very little data exists on the visco-elastic properties of the living human brain
      tissue and collection of such data is vital for mechanical modelling. The purpose
      of this study was to measure the rate of relaxation of brain that has been
      compressed by tumour after surgical decompression. Seven patients who underwent a
      lobectomy for an intracranial space occupying lesion were included in the study.
      All underwent two CT scans within the first 24 h after the surgery. Volumes of
      the residual void on the serial CT scan were calculated using tools in the image
      acquisition software. There was a rapid expansion of the brain to fill up the
      void space in the first 24 h after surgery. The average rate of relaxation of the
      compressed brain is 2.25(0.76 - 6.64) ml/h. The graphs plotted for the volume of
      the void space against the time after surgery when the CT scans were done can be
      used to further explore the dynamics of brain relaxation. The rate of brain
      relaxation in the first 24 h after removal of a mass lesion averages 2.25(0.76 -
      6.64) ml/h in this study. Further studies using more frequent data collection
      would allow for more accurate definition of the rate of relaxation.

PMID- 16801048
TI  - Intracranial plasma cell-granuloma with extensive ossification.
AB  - Intracranial plasma-cell granuloma is non-neoplastic proliferation of plasma
      cells which occurs rarely. We present an unusual case of an 18-year-old female
      patient with extensively ossified intracranial plasma-cell granuloma. Computed
      Tomography (CT) and Magnetic Resonance Image (MRI) demonstrated a left
      frontoparietal mass with extensive calcification. The lesion was removed
      subtotally. Histopathological findings revealed diffuse inflammatory cells
      consisting mostly of reactive plasma cells, histiocytes and neutrophils, several
      lymphocytes, lymphoplasmacytic cells, a few eosinophils throughout the dura and
      adjacent brain. Widespread psammomatous and dystrophic calcifications, and very
      extensive ossification with trabecular bone formation were present within the
      lesion. In the case of an intracranial mass lesion with calcification, plasma
      cell granuloma, although rare, should be included in the differential diagnosis.

PMID- 16801050
TI  - Giant traumatic pseudoaneurysm of the superficial temporal artery: treatment
      challenges and case review.
AB  - Traumatic pseudoaneurysms of the superficial temporal artery are uncommon. They
      present to a variety of specialities - orthopaedics, ear, nose and throat,
      neurosurgery, maxillofacial, plastic surgery, vascular surgery and dermatology.
      Experience managing these lesions is therefore limited and diluted. We present a
      case of a giant, traumatic pseudoaneurysm of the superficial temporal artery,
      which required the unusual approach of staged surgical excision.

PMID- 16801049
TI  - Psychosis-like syndrome associated with intermittent intracranial hypertension
      caused by a large arachnoid cyst of the left temporal lobe.
AB  - Lesions on certain brain areas can cause psychiatric signs. Symptomatic arachnoid
      cysts can produce a variety of symptoms like headache, seizures, increased ICP,
      and rarely psychiatric disorders. We report a case of a young woman with a left
      temporal lobe arachnoid cyst, presented with headache and an atypical psychosis.
      A 72-h epidural ICP recording revealed incidental elevation of ICP. After a
      permanent shunt was placed, patient's symptoms improved substantially, and
      antipsychotic medication was significantly reduced.

PMID- 16801051
TI  - Hemifacial spasm associated with focal bone hyperostosis.
AB  - We present a very rare case of hemifacial spasm in a 58-year-old patient who was
      predisposed by focal temporal bone hyperostosis. The patient presented with a 6
      year history of progressive left hemifacial spasm, unresponding to the
      conservative treatment. She underwent a typical microvasular decompression
      procedure, during which an unusual local hyperostosis of the interior surface of
      the left temporal bone was found, distorting the adjacent AICA and causing
      significant pressure on the facial nerve. The postoperative course was uneventful
      and in the 24-month follow up, the patient is spasm free.

PMID- 16801052
TI  - Aneurysmal subarachnoid haemorrhage in a patient with thyrotoxicosis.
AB  - A case of subarachnoid haemorrhage secondary to rupture of an intracranial
      aneurysm occurring in a patient with new-onset, frank thyrotoxicosis is
      described. This unusual case highlights the dilemma of whether to continue beta
      blockers such as propanolol for frank thyrotoxicosis, or whether to assign higher
      priority to maintaining adequate cerebral perfusion pressure in established
      ischaemic deficit due to vasospasm. In a complicated case such as this, the
      Maudsley Mentation Test score and perfusion CT scanning are two useful adjuncts
      for the early detection and evaluation of the course of ischaemic deficit.

PMID- 16801053
TI  - Intracranial metastasis from medullary carcinoma of the thyroid 25 years after
      primary surgery.
AB  - Medullary carcinoma of the thyroid is an uncommon tumour. In most patients, it is
      confined to the neck with or without involvement of the local cervical nodes. It
      rarely metastasizes to the mediastinum, lungs or liver. Intracranial metastasis
      is extremely rare with very few reported cases in the literature. We report an
      unusual case of an intracranial metastasis from a medullary carcinoma of the
      thyroid that occurred 25 years after primary surgery. We discuss the unusual
      features of our case together with a review of the literature.

PMID- 16801054
TI  - A healthy lifestyle leading to a rare ventriculo-peritoneal shunt complication.

PMID- 16801055
TI  - Cervical cord presyrinx.

PMID- 16801056
TI  - Dealing with dysfunctional doctors.

PMID- 16801058
TI  - Reanalysis of the timing of cauda equina surgery.

PMID- 16801065
TI  - Multiple functions of tissue inhibitors of metalloproteinases (TIMPs): new
      aspects in hematopoiesis.
AB  - The extracellular matrix (ECM), the product of stromal cells, is now thought to
      make a dynamic network in tissues. Stromal cells can support other cells not only
      by direct contact but also via this ECM network. The regulated turnover and
      remodeling of ECM needs both ECM degrading enzymes named matrix
      metalloproteinases (MMPs) and their inhibitors called tissue inhibitors of
      metalloproteinases (TIMPs). Through an understanding of their molecular
      structure, the nature of the enzymic activity of MMPs and the inhibitory action
      of TIMPs against MMPs have been well elucidated. Considering their potent
      inhibitory action against MMPs, TIMPs are thought to play an important role in
      maintaining ECM. However, other unique functions of TIMPs have been reported,
      such as erythroid potentiating activity, cell growth-promoting activity,
      embryogenesis-stimulating activity, steroidogenesis-stimulating activity and so
      on. This review covers this new field, and discusses what role TIMPs can play in
      controlling life. In the second part, we briefly introduce our recent date on
      TIMPs and hematopoiesis. Because TIMPs have a dual function, i.e. a potent
      inhibitory action against MMPs and cell growth promoting action, TIMPs are good
      candidates for tissue fibrosis. Our recent measurements of TIMP-1 and TIMP-2
      levels using serum and plasma from patients with platelet number disorders and
      cultured medium from various leukemia cell lines, shows that platelets are a rich
      source of TIMPs and that TIMP-1 is secreted in large amounts by megakaryoblastic-
      and erythro-leukemia cell lines. Proliferation of bone marrow fibroblasts can be
      stimulated by TIMP-1 and TIMP-2. Taken together, TIMPs might be one of the
      important factors for the process of myelofibrosis in some pathological
      conditions.

PMID- 16801066
TI  - Serum levels of thrombopoietin and stem cell factor in acute leukemia patients
      with chemotherapy-induced cytopenia and complicating infections.
AB  - Thrombopoietin (Tpo) and stem cell factor (SCF) are growth factors for
      megakaryocyte progenitor cells and can also modulate platelet function. We have
      characterized variations in serum levels of these two cytokines in acute leukemia
      patients undergoing intensive chemotherapy. Compared with healthy controls, serum
      Tpo levels were significantly increased prior to consolidation chemotherapy, and
      serum levels were correlated to peripheral blood platelet counts. Serum Tpo
      levels increased when the patients developed chemotherapy-induced cytopenia, and
      a further increase was observed during complicating bacterial infections. In
      contrast to Tpo, SCF serum levels in leukemia patients did not differ from
      healthy controls neither before chemotherapy nor during the period of
      chemotherapy-induced cytopenia. Serum levels of Tpo (and possibly SCF) may
      influence thrombopoiesis and/or platelet functions in patients undergoing
      intensive chemotherapy for acute leukemia.

PMID- 16801067
TI  - The interaction of ancrod with human platelets.
AB  - Ancrod, a serine protease purified from the venom of Agkistrodon rhodostoma, has
      been used as a therapeutic anticoagulant for a number of indications, including
      replacement of heparin in patients with heparin-induced thrombocytopenia. Ancrod
      has similar fibrinolytic activity to thrombin, but ancrod specifically cleaves
      only the alpha chain of fibrinogen, producing the characteristic fibrinopeptides
      A, AP and AY. Because ancrod has been used in patients with heparin-induced
      thrombocytopenia, it is important to ensure that ancrod does not directly affect
      the platelets and potentially increase the hemostatic effect. The effect of
      ancrod on platelets has not been well established, and there is not agreement in
      published studies. Additionally, some of the studies are over 15 years old and
      pre-date sensitive assays such as glycoprotein analysis. For these reasons, we
      investigated the interaction of ancrod with human platelets using direct and
      indirect, functional and biochemical techniques. Incubation of platelets with
      ancrod alone did not induce platelet aggregation or the release of dense-granule
      contents. Pre-incubation of platelets with ancrod did not augment or inhibit the
      maximal aggregation achieved with thrombin, nor did it affect the amount of
      serotonin release from dense granules caused by activation by thrombin. Studies
      of ancrod-treated platelets using monoclonal antibody-mediated
      radioimmunoprecipitation demonstrated that high concentrations of ancrod did not
      cause measurable cleavage of either the glycoproteins Ib-IX or IIb-IIIa.
      Incubation of radiolabeled platelets with ancrod-treated plasma also had no
      effect on the platelet glycoproteins, indicating that ancrod does not indirectly
      affect the major surface receptors. Direct binding studies using radiolabeled
      ancrod did not demonstrate specific binding to the platelet surface. Together
      these studies indicate that ancrod does not directly affect nor bind to platelets
      in vitro. The hypo-coagulant state and subsequent platelet function defect
      resulting from the use of ancrod appears to be limited to the removal of
      fibrinogen from the circulation.

PMID- 16801068
TI  - White cell retention compared with platelet retention in the filterometer:
      controls and abnormal states.
AB  - Platelets and white cells contribute to thrombus formation. In the filterometer,
      platelet retention in normal citrated blood increases from 47.5% at 0-5 s to
      81.5% at 20-40 s. White cell retention is normally closely related to platelet
      retention at 0-5 s but less so at 20-40 s. However at 20-40 s the number of white
      blood cells (WBC) retained has decreased relative to 0-5 s. This apparent paradox
      is now further explored using antibodies to glycoprotein (GP) Ib, to von
      willebrand factor (vWf) and to GPIIb-IIIa together with observations on a number
      of clinical conditions with abnormal platelet retention. In citrated blood,
      platelet retention of 0-5 s was significantly decreased relative to normal in von
      Willebrand's disease, in aortic valve stenosis and with the addition of anti-vWf
      GPIb and minimally with anti-GPIIb-IIIa antibodies. WBC retention of 0-5 s in
      these groups was always 41 2%. However when platelet retention 0-5 s was raised
      (pregnancy and venous occlusion), white cell retention was also raised. At 20-40
      s in all the nine conditions studied, the white cell and platelet retention were
      closely related, but the percentage WBC retained decreased relative to the
      platelet retention. Granulocyte retention was higher than lymphocyte retention,
      but both cell types were similarly affected. We conclude that the platelets are
      retained as previously described. The white cells (all types) initially bind at
      least in part in an independent unexplained way (0-5 s). Thereafter the degree of
      platelet activity (retention %) largely determines the degree of WBC retention.
      This is probably due to a proportional amount of P-selectin liberated by the
      activated platelets.

PMID- 16801069
TI  - Activated platelets mediate Staphylococcus aureus deposition on subendothelial
      extracellular matrix: the role of glycoprotein Ib.
AB  - Extracellular matrix (ECM) derived from bovine corneal endothelial cells was used
      as a model to study the role of platelets in Staphylococcus aureus interaction
      with the vascular subendothelium. In whole blood, S. aureus activated platelets,
      as demonstrated by P-selectin expression on the platelet membrane. Subjecting
      platelet-rich plasma (PRP) to the ECM under oscillatory conditions resulted in
      platelet adhesion and aggregation. S. aureus increased platelet deposition on ECM
      depending on the bacterium-platelet ratio. Scanning electron microscopy revealed
      that S. aureus adhered to and formed clusters on ECM-bound platelets. These
      findings were confirmed by using [3H]thymidine-labeled bacteria that adhered to
      the surface more extensively after deposition of platelets on ECM. Platelet pre
      treatment with prostaglandin E1 resulted in inhibition of bacterial adherence.
      Glycoprotein (GP)Ib was involved in the bacterium-platelet interaction, as
      indicated by the following: (i) S. aureus diminished the binding of GPIb but not
      of GPIX or GPIIb-IIIa monoclonal antibodies (Mab) to washed fixed platelets; (ii)
      GPIb Mab inhibited S. aureus -induced platelet aggregation in a dose-dependent
      fashion; (iii) blockade of von Willebrand factor (vWf) binding to GPIb by a
      recombinant vWf fragment reversed the enhanced platelet deposition on ECM in the
      presence of S. aureus but did not affect platelet deposition in the absence of
      bacteria. The results indicate that S. aureus activates platelets and promotes
      their deposition on ECM via GPIb-dependent mechanism and that adherent platelets
      mediate S. aureus deposition on the subendothelium. These interactions might play
      a role in the pathogenesis of bacterial endocarditis.

PMID- 16801070
TI  - Inhibitory effect of glyburide on thrombin-induced platelet aggregation and
      phosphoinositide metabolism in normal human platelets.
AB  - We previously reported the effects of diet, sulphonylureas or insulin on thrombin
      induced platelet aggregation, phosphoinositide metabolism and protein
      phosphorylation in non-insulin-dependent diabetes mellitus (NIDDM) patients. To
      clarify the mechanism of glyburide and insulin on platelet function, here we
      studied the in vitro effects of glyburide and insulin on thrombin-induced
      metabolic changes using normal human platelets. Platelet aggregation stimulated
      with <0.5 U/ml thrombin, 0.75-3 microM adenosine diphosphate (ADP) or 1 microg/ml
      collagen was significantly lower in glyburide-treated platelets, but not in
      insulin-treated platelets, than in untreated ones (control). Thrombin-induced
      incorporation of 32P radioactivity into phosphatidic acid (PA) in glyburide
      treated platelets was lower than that in control but not in insulin-treated
      platelets. Phosphorylated proteins of platelets induced by thrombin and 12- O 
      tetradecanoylphorbol 13-acetate (TPA) in glyburide-treated platelets were
      suppressed, but not in insulin-treated platelets, compared with control. These
      results suggest that glyburide induces suppression of thrombin-induced activation
      of phospholipase C, which mediates hydrolysis of PIP and PIP(2) and production of
      PA, and subsequently inhibits platelet aggregation.

PMID- 16801071
TI  - Possible mechanisms of the altered platelet volume distribution in type 2
      diabetes: does increased platelet activation contribute to platelet size
      heterogeneity?
AB  - A direct consequence of increased platelet sensitivity in diabetes mellitus might
      be augmented release of platelet granule contents, which, in turn, may lead to
      the formation of a platelet volume gradient, increased platelet turnover and
      reduced survival of platelets from diabetic individuals. In this study we
      addressed the question whether diabetes-induced and lipid fluidity-mediated
      changes in platelet receptor exposure and accessibility might be part of a
      general mechanism underlying the increased rate of platelet ageing and reduced
      platelet survival in diabetes. Diabetic individuals showed higher numbers of
      platelets of extreme dimensions: very small platelets and larger platelets were
      more frequent compared to controls ( P(chi(2))< 0.03). The shifts in platelet
      volume distributions were paralleled by decreased expression of the alpha subunit
      of glycoprotein Ib (by up to 17%, P < 0.01) in platelet membranes from diabetic
      patients, increased expression of P-selectin in thrombin-stimulated diabetic
      platelets (P< 0.02), an increased number of platelet microparticles in diabetic
      individuals (P< 0.05 or P< 0.03 for resting or stimulated platelets,
      respectively), and reduced platelet membrane fluidity (by 5.2 +/- 0.6%, P< 0.01).
      We suggest that the distinct bimodality of platelet distribution in diabetic
      patients might arise from accelerated thrombopoiesis in diabetic subjects, and
      this is supported by the demonstration of elevated fractions of reticulated (rich
      with residual RNA) platelets in diabetic patients (14.6 +/- 5.6% vs 8.1 + 2.1%
      p(u) < 0.025). Overall, our results point to a fluidity-mediated platelet
      hypersensitivity and accelerated rate of platelet production in subjects with
      type 2 diabetes mellitus, which results in a greater number of very large and
      hypersensitive younger platelets and a more abundant fraction of small exhausted
      platelets.

PMID- 16801072
TI  - Platelet density in essential thrombocythemia and polycythemia vera.
AB  - This study aims to compare platelet density in myeloproliferative disorders
      (essential thrombocythemia (ET) and polycythemia vera (PV)) with platelet density
      of healthy subjects. Platelet density peaks were determined using a specially
      designed apparatus for scanning light transmission variations along test tubes
      containing density-separated platelets. Eighteen patients with myeloproliferative
      disorders (nine ET and nine PV) were compared with a control group consisting of
      12 healthy volunteers. Compared with healthy volunteers, patients with
      myeloproliferative disorders had significantly lower platelet peak density ( P<
      0.001). It is concluded that determination of peak platelet density may be a
      useful tool for excluding ET and PV. A high platelet density peak makes a clonal
      disorder less likely and a low density peak would confirm the suspicion.

PMID- 16801073
TI  - Unstable signal of aequorin-indicated free (Ca(2+))(i) in EGTA-permeabilized
      human platelets.

PMID- 16801074
TI  - Effect of naftazone on in vivo platelet function in the rat.
AB  - The aim of this study was to investigate the in vivo effects of 50 mg/kg (i.p.)
      naftazone or ticlopidine on platelet functions in the rat. An automated isotope
      monitoring system (Aims plus) was used to determine the height of platelet
      aggregation and disaggregation (measured by the area under the curve, AUC) of
      111indium-labelled platelets activated by ADP (10 microg/kg i.v.) or collagen (50
      microg/kg i.v.). Fibrinogen-binding experiments were carried out with activated
      platelets in whole blood and measured by flow cytometry. Naftazone reduced the
      height of platelet aggregation induced by ADP compared with controls (P = 0.024).
      Ticlopidine-treated rats gave similar results (P = 0.008). Platelet
      disaggregation, following the aggregation induced by collagen, was significantly
      increased in naftazone-treated rats compared with controls (P = 0.003). Similar
      results were observed with ticlopidine-treated rats (P = 0.002). Fibrinogen
      binding to 2.5 or 5 microM ADP-stimulated platelets, from naftazone-treated rats,
      were significantly reduced compared with controls (P = 0.05 and 0.04
      respectively). These results show that naftazone has similar inhibitory effects
      on rat platelet functions as ticloplidine. In conclusion, naftazone could be a
      useful agent to modulate platelet function in patients with cardiovascular
      disease.

PMID- 16801075
TI  - 'Association of platelet function in hypertensive patients with left ventricular
      hypertrophy'.

PMID- 16801076
TI  - The significance of platelet-derived growth factors for proliferation of vascular
      smooth muscle cells.
AB  - Platelets are important in acute thrombotic occlusion of injured vessels, e.g.,
      subsequent to angioplasty. In contrast to these acute events of thrombus
      formation, much less is known about the significance of platelets for the control
      of smooth muscle cell (SMC) proliferation. A body of experimental and clinical
      evidence indicates an involvement of platelets in the pathology of
      atherosclerosis and restenosis. However, the precise role of platelet-derived
      growth factors for SMC proliferation in atherosclerotic and restenotic vessels is
      not clear and many questions remain unresolved. Platelet-dependent SMC
      mitogenesis is determined by a coordinate action of several classes of mitogenic
      factors which are either released from storage pools or generated upon platelet
      activation. Although platelet-derived growth factor (PDGF) is considered to be
      the most important platelet mitogen it is very likely that yet unknown factors
      and mechanisms are involved. Differential (stimulatory or inhibitory) effects on
      SMC growth and differentiation have been reported for different platelet-derived
      growth factors. Thus, for the overall response, complex interactions between
      multiple factors need to be considered. In addition, multicellular interactions,
      e.g., between platelets and endothelial cells may modulate the effects of
      platelet-derived factors on SMC mitogenesis. Taken together, the mechanisms of
      platelet-dependent SMC proliferation need to be reevaluated. The assessment of
      the precise role of platelet mitogens in the complex proliferative repair
      mechanisms of an injured vessel wall clearly requires further studies.

PMID- 16801077
TI  - Benzalkonium chloride interferes with energy production, secretion and morphology
      in human blood platelets.
AB  - Benzalkonium chloride (BC) is a bactericidal compound used as a topical
      antiseptic and as a preservative in various products for local treatment, e.g.,
      eye and nose drops. BC is toxic to human cells, including those of the
      respiratory mucosa. Few studies have, however, focused on what cellular functions
      BC interferes with. The effects of BC were studied on washed human blood
      platelets in vitro . Cellular energy production as well as secretion were
      studied. Incubation of platelets with BC resulted in rapid swelling and toxic
      morphological changes. After incubation with BC oxidation of [1-14C] palmitate
      was inhibited, and both lactate dehydrogenase and endogenous serotonin were
      spontaneously released. Thrombin-induced secretion of serotonin was strongly
      reduced after BC exposure. Histological changes with increased size, spherical
      form, decreased numbers of pseudopodia, loss of an intact continuous tubulus
      system and reduced number of granules were found by scanning and transmission
      electron microscopy. It is concluded that the toxic effects of BC are because of
      interference with membrane function and energy production.

PMID- 16801078
TI  - Differences in the platelet proaggregatory activity of immune complexes isolated
      from patients with myocardial infarction or pulmonary cancer.
AB  - Immune complexes were isolated immediately after the onset of the symptoms of
      myocardial infarction on an anti-Clq affinity column. The platelet proaggregatory
      effects of these immune complexes were compared with those isolated from patients
      suffering from pulmonary cancer. A markedly increased proaggregatory effect of
      immune complexes derived from patients with myocardial infarction and changes in
      the sensitivity of platelets from healthy volunteers to PGI(2) (prostacyclin) and
      PGD(2) were found. In contrast, immune complexes from patients with pulmonary
      cancer did not show any significant effect. The antigenic part of immune
      complexes is probably relevant in the induction of platelet aggregation.

PMID- 16801079
TI  - Studies on the biological effects of ozone: 9. Effects of ozone on human
      platelets.
AB  - During the course of ozonated autohaemotherapy (O3-AHT) using heparin as an
      anticoagulant, it was occasionally observed that a few clots were retained in the
      filter during blood reinfusion. This observation prompted an investigation on the
      effect of ozone (O3) on human platelets. We have now shown, both by biochemical
      and morphological criteria, that heparin in the presence of O3 can promote
      platelet aggregation. In contrast, after Ca(2+) chelation with citrate, platelet
      aggregation is much reduced. The potential role of the transient formation of
      hydrogen peroxide (H2O2) in the presence of Ca2+ with the possible expression of
      adhesion molecules is briefly discussed.

PMID- 16801080
TI  - Phorbol ester induces a transient increase in alpha(5)beta(1)-mediated adhesion
      of the megakaryoblastic cell line CHRF 288-11.
AB  - This study investigated the mechanism by which treatment of the CHRF 288-11
      megakaryoblastic cell line with phorbol myristate acetate caused a transient
      increase in adhesion. The adhesion to tissue culture plastic occurred within 4 h
      and could be reversed by treatment with RGDS-peptide suggesting the involvement
      of one or more RGD-binding integrins. Ligand-binding adhesion assays suggested
      that PMA-induced CHRF 288-11 cells had very little affinity for fibrinogen, a low
      affinity for vitronectin and a much higher affinity for fibronectin. Further
      adhesion assays performed in the presence of various integrin antagonists or
      inhibiting monoclonal antibodies demonstrated that the fibronectin-mediated cell
      adhesion is via the alpha beta , fibronectin receptor, integrin. Flow
      cytometrical investigations showed that this increase in alpha(5)beta(1)-adhesion
      on CHRF 288-11 cells following PMA stimulation was not brought about by an
      increase in alpha(5)beta(1)-integrin expression and inferred that increased
      adhesion is achieved by an increase in alpha(5)beta(1) ligand-binding function.
      These findings confirm other reports using different cells that the expression
      and function of integrins may play an important role in megakaryocytopoiesis.
      Modulation of integrin function may facilitate the migration of maturing
      megakaryoblasts in the bone marrow stroma before their movement through the sinus
      wall and into the blood stream. The report demonstrates that the CHRF 288-11
      megakaryoblastic cell line is a useful model for investigating some aspects of
      these phenomena.

PMID- 16801081
TI  - Increased platelet reactivity to the aggregatory effect of platelet activating
      factor, in vitro, in patients with heterozygous familial hypercholesterolaemia.
AB  - Patients with familial hypercholesterolaemia (FH) present with high plasma total-
      and low density lipoprotein (LDL)-cholesterol levels and develop premature and
      often severe atherosclerosis. Elevations of total- and LDL cholesterol levels are
      not only related to an increased risk of atherosclerosis, but may also exert
      prothrombotic effects via platelet activation leading to acute coronary events.
      In the present work, the platelet response to the aggregatory effect of platelet
      activating factor (PAF) in relation to the plasma PAF-acetylhydrolase (PAF-AH)
      activity and to their lipidemic profile was studied in 20 heterozygous FH
      patients. The PAF EC(50) aggregation values in the patient group were
      significantly decreased ( P < 0.03) compared with the control group (19.5 5.2 nM
      and 30.4 7.2 nM, respectively). Moreover, the maximal percentage of aggregation
      to 100 nM PAF was significantly increased in the patient group compared with
      controls (26.5 8.2% vs 15.2 3.1%, respectively, P < 0.03). Both platelet
      aggregation parameters were correlated to the plasma total- and LDL-cholesterol
      levels, as well as to the apolipoprotein B (apo B) levels. The maximal percentage
      of aggregation to 10 microM ADP was also significantly increased in the patient
      group compared with controls (51.5 10.3% vs 32.4 9.0%, respectively, P < 0.02)
      but was not correlated to any plasma lipid parameter. The total plasma PAF-AH
      activity in the heterozygous FH patients was significantly higher compared with
      controls (109.8 15.9 nmol/ml per min vs 68.4 18.0 nmol/ml per min, respectively,
      P < 0.0001), whereas the HDL-associated PAF-AH activity did not differ
      significantly between the two groups. Our results suggest that the increased
      aggregatory response of platelets to PAF despite the significantly higher plasma
      PAF-AH activity, could be an important factor contributing to the higher
      atherogenicity and incidence of acute coronary events observed in patients with
      heterozygous FH.

PMID- 16801082
TI  - Can the Platelet Function Analyzer (PFA)-100 test substitute for the template
      bleeding time in routine clinical practice?
AB  - The bleeding time (BT) is widely used in clinical medicine as a screening test of
      platelet function, although its deficiencies in such a role are well recognized.
      The Platelet Function Analyzer (PFA)-100 measures the ability of platelets
      activated in a high-shear environment to occlude an aperture in a membrane
      treated with collagen and epinephrine (CEPI) or collagen and ADP (CADP). The time
      taken for flow across the membrane to stop (closure time) is recorded. This study
      compared the PFA-100 with the BT as a screening test of platelet dysfunction in
      113 hospital inpatients. The PFA-100 test was performed initially using the CEPI
      cartridge; CADP tests were performed on those with abnormal (> 163 s) CEPI
      closure times. Whole blood platelet aggregation studies and chart review were
      performed on patients in whom the BT and PFA-100 results did not agree.Abnormal
      bleeding times and PFA-100 results were obtained in 20.4% and 35.4% of patients,
      respectively. The results of BT and PFA-100 agreed in 74.3% of patients. Of the
      29 patients in whom the BT and PFA-100 results were discordant, whole blood
      platelet aggregation studies supported the PFA-100 result in 25 (86.2%). The PFA
      100 was more sensitive to aspirin-induced platelet dysfunction and was more
      rapidly and cheaply performed than the BT. Since the PFA-100 test reflects
      platelet function better than the BT, we conclude that this test could replace
      the BT as a first-line screening test for platelet dysfunction in clinical
      practice.

PMID- 16801083
TI  - 5-Fluorouracil induces defects in platelet function.
AB  - Platelet factor-3 (PF(3)) availability and platelet aggregation to ADP (4
      micromol/l) and adrenaline (1.2 micromol/l) were evaluated in patients being
      treated with 5-fluorouracil (5-FU) for gastrointestinal malignancy. It produced a
      significant reduction in platelet aggregation and platelet factor-3 (PF(3))
      availability ( P < 0.001) without being associated with thrombocytopenia. The
      changes in platelet aggregation occurred during the first week of chemotherapy
      and continued with subsequent courses. This acquired abnormality may be
      responsible for a haemorrhagic diathesis even without obvious thrombocytopenia.
      Study of platelet function is important and may be considered to assess the
      haematological toxicity in patients being treated with systemic 5-FU therapy.

PMID- 16801085
TI  - The influence of organic peroxides on platelet aggregation and sensitivity to
      nitric oxide.
AB  - The effects of oxidative stress, induced by water-soluble and lipid peroxides, on
      platelet reactivity and platelet sensitivity to nitric oxide were investigated.
      Hydrogen peroxide and cumene hydroperoxide potentiated thrombin-induced platelet
      aggregation. In contrast, 15(S)-hydroperoxyeicosatetraenoic acid had no such
      effect, while 12(S)-hydroperoxyeicosatetraenoic acid inhibited platelet
      reactivity. All of the peroxides tested were found to decrease platelet
      sensitivity to nitric oxide, although the mechanisms by which the various
      peroxides altered platelet sensitivity to nitric oxide were different. The water
      soluble peroxides opposed the actions of nitric oxide without affecting cyclic
      GMP levels, while 15(S)-hydroperoxyeicosatetraenoic acid caused a significant
      reduction in the concentration of cyclic GMP formed in response to NO. The data
      from this study demonstrate that water-soluble and lipid peroxides both affect
      platelet reactivity and regulation, but by different mechanisms. Thus, caution
      should be exercised when selecting peroxides to be used as models of oxidative
      stress.

PMID- 16801084
TI  - 1-Deamino (8-D-arginine) vasopressin infusion partially corrects platelet
      deposition on subendothelium in Bernard-Soulier syndrome: the role of factor
      VIII.
AB  - The mechanism of the transient beneficial effect of 1-deamino(8-D-arginine)
      vasopressin (dDAVP) infusion in the hemostasis of some BSS patients is not fully
      understood. We have studied the effect of dDAVP infusion in a BSS patient using
      an ex vivo perfusion system. Additional coagulation and flow cytometry studies
      were also performed. Prolonged bleeding time (> 30 min) was not affected by dDAVP
      infusion. However, perfusion experiments performed with low molecular weight
      heparin anticoagulated blood (which permits the study of fibrin deposition on
      perfused subendothelium) showed a significant increase in platelet deposition
      (6.2% before dDAVP infusion; 20.3% after) and fibrin formation. dDAVP infusion
      also caused an increase in prothrombin consumption compared with base line values
      (33 vs 46%). Flow cytometry studies of the patients platelets showed no changes
      in binding of monoclonal antibodies against CD41, CD36, CD62P or CD63. The
      increase in thrombus formation observed in perfusions may be dependent on FVIII
      since it could be reproduced by adding purified free or von Willebrand factor
      (vWf)-associated FVIII to the patient's blood in vitro. The shortening effect of
      dDAVP on bleeding time observed in some Bernard-Soulier syndrome patients might
      be related to an increase in factor FVIII levels induced by dDAVP infusion.

PMID- 16801086
TI  - A flow cytometric assay for the study of dense granule storage and release in
      human platelets.
AB  - The clinical manifestations of platelet dense ( delta ) granule defects are easy
      bruising, as well as epistaxis and bleeding after delivery, tooth extractions and
      surgical procedures. The observed symptoms may be explained either by a decreased
      number of granules or by a defect in the uptake/release of granule contents. We
      have developed a method to study platelet dense granule storage and release. The
      uptake of the fluorescent marker, mepacrine, into the platelet dense granule was
      measured using flow cytometry. The platelet population was identified by the size
      and binding of a phycoerythrin-conjugated antibody against GPIb. Cells within the
      discrimination frame were analysed for green (mepacrine) fluorescence. Both
      resting platelets and platelets previously stimulated with collagen and the
      thrombin receptor agonist peptide SFLLRN was analysed for mepacrine uptake. By
      subtracting the value for mepacrine uptake after stimulation from the value for
      uptake without stimulation for each individual, the platelet dense granule
      release capacity could be estimated. Whole blood samples from 22 healthy
      individuals were analysed. Mepacrine incubation without previous stimulation gave
      mean fluorescence intensity (MFI) values of 83+/-6 (mean +/- 1 SD, range 69-91).
      The difference in MFI between resting and stimulated platelets was 28+/-7 (range
      17-40). Six members of a family, of whom one had a known delta -storage pool
      disease, were analysed. The two members (mother and son) who had prolonged
      bleeding times also had MFI values disparate from the normal population in this
      analysis. The values of one daughter with mild bleeding problems but a normal
      bleeding time were in the lower part of the reference interval.

PMID- 16801087
TI  - Influence of intracellular chelating agents on formation of spike-like pseudopods
      by human platelets.
AB  - Recent reports have suggested that spike-like pseudopods develop on platelets
      loaded with intracellular chelating agents during glass activation, and proposed
      that the extensions are caused by an unusual organization of newly assembled
      actin filaments. The present study has reexamined this hypothesis. Platelets
      loaded with one of the chelating agents, Quin II or BAPTA, seldom formed spike
      like pseudopods when exposed to glass at 37 C for 30-60 min. However, when
      chilled and rewarmed the Quin II-or BAPTA-loaded platelets readily developed one
      or several spike-like extensions after a 30-60-min exposure to glass or on
      shaking in suspension. Thin section and negative-stain electron microscopy
      demonstrated that the major constituents of spike-like pseudopods were
      microtubules. Unusual coils of actin filaments were not observed. The observation
      was confirmed by immunofluorescence microscopy employing an anti-tubulin antibody
      and fluorescein-conjugated antimouse IgG. Cytochalasin B, an agent that inhibits
      new actin filament formation had virtually no effect on spike formation by
      chilled-rewarmed, Quin II- or BAPTA-loaded cells, whereas prior exposure to
      vincristine, an agent that dis-assembles microtubules and prevents their
      reformation, blocked spike development. Taxol, a drug that stabilizes
      microtubules and prevents their disassembly by cold or vincristine, prevented
      spike formation. Results indicate that microtubule assembly is the major cause of
      spike-like pseudo-pod formation, and the increased assembly may be due to binding
      of free cytoplasmic calcium by intracellular chelating agents.

PMID- 16801088
TI  - Do determinants of platelet function co-segregate with genetic markers of type 1
      diabetes mellitus?
AB  - This study examined the significance of selected parameters of primary
      haemostasis to discriminate between relatives of children with insulin-dependent
      diabetes mellitus (IDDM). Platelet function, including markers of spontaneous and
      agonist-induced platelet activation (CD62), platelet consumption (microparticles)
      and clumping (aggregates), as well as selected parameters of the fibrinolytic
      system (t-PA and PAI-1), were studied in IDDM children ( n = 45), their parents (
      n = 65), siblings ( n = 17) and unrelated healthy controls ( n = 51). The
      fraction of activated platelets circulating in whole blood amounted to 4.3 +/-
      2.1% in IDDM children, and significantly exceeded the level found in parents (1.3
      +/- 0.7%, P < 0.002), siblings (1.2 +/- 1.0%, P < 0.002), and controls (1.2 +/-
      0.6%, P < 0.002). Furthermore, an enhanced formation of platelet microparticles
      was observed in the IDDM group, both in resting platelets and also when platelets
      were stimulated with thrombin. Significantly decreased total PAI-1 occurred in
      IDDM children ( P < 0.02 versus parents); also slightly lowered active PAI-1 and
      t-PA antigen were noticed in IDDM subjects compared to other groups, however, the
      differences were not statistically significant. To assess dissimilarities between
      the groups of subjects we applied the forward stepwise model of discriminant
      function analysis, which included platelet flow cytometry parameters. The best
      separation and the highest discrepancy (expressed as the so called squared
      Mahalanobis distances, d ) was M revealed between controls and IDDM patients ( P
      < < 0.0001) and between controls and parents ( P < < 0.0001). The values of d
      found between IDDM children and their siblings (P < 0.001), as well as parents (
      P < 0.01), were M of much lower significance. The finding that the control group,
      representing unrelated subjects, remains particularly well separated from the
      other groups, more or less clustered together, implies the possible involvement
      of genetic factor(s) which might potentially affect platelet activation and
      reactivity. In addition, the distinguished distribution of HLA DQAI(52) and HLA
      DQBI(57) genotypes in the groups further validates the suspicion that the altered
      platelet function and response in diabetes might be associated with some
      independent genetic factor(s), and is not likely to result from HLA DQAI(52) and
      HLA DQBI(57) impact.

PMID- 16801089
TI  - A shear-induced in vitro platelet function test can assess clinically relevant
      anti-thrombotic effects.
AB  - Morphological features of haemostatic plugs formed in vitro under high shear
      forces were investigated. Electron microscopy confirmed the relevance of such
      haemostatic plug to a platelet-rich arterial thrombus, which is formed in vivo .
      In rat blood samples, the effects of anticoagulants and various antiplatelet
      agents on platelet reactivity (rate of haemostatic plug formation) and subsequent
      coagulation of the flowing blood were investigated. Haemostasis did not occur in
      citrated blood, and heparin greatly inhibited the shear-induced platelet
      reaction. Aspirin (1 mM), a thromboxane A(2) receptor antagonist (5 microM), a
      stable prostacyclin (0.55 nM), a stable prostaglandin E(1) (141 nM) and a
      phosphodiesterase inhibitor (100 microM) were tested. All these agents exerted
      significant inhibitory effect on shear-induced platelet reaction, including the
      inhibition of the very first phase of platelet plug formation, due to aggregation
      of shear-activated platelets. Except for the phosphodiesterase inhibitor, which
      prolonged clotting time, none of the above agents affected dynamic coagulation.
      These results suggest that the employed in vitro shear-induced
      thrombosis/haemostasis test can reveal in vivo the antithrombotic effect of
      various agents independently of their mechanism of action.

PMID- 16801090
TI  - Selenium compounds inhibit the biological activity of blood platelets.
AB  - The action of inorganic forms of selenium (Se) on blood platelet aggregation,
      secretion and the arachidonate pathway in vitro was studied. It was shown that
      sodium selenite, after 30 min preincubation, inhibited platelet aggregation
      induced by 0.1 U/ml of thrombin and by 10 microM ADP (about 30% inhibition of
      aggregation after pretreatment of platelets with 10(-4) M of Se). Contrary to
      sodium selenite, sodium selenate did not affect the platelet aggregation induced
      by either agonist. Pretreatment of blood platelets with sodium selenite resulted
      in a statistically significant decrease in adenine nucleotide secretion ( P <
      0.01) and release of malonyldialdehyde (MDA), produced in equal amounts to TXA(2)
      , in thrombin-stimulated platelets ( P <0.001). However, selenite did not change
      the level of MDA/TXA(2) in sodium arachidonate-stimulated platelets. We conclude
      that the inhibitory effects of sodium selenite on platelet activation could be
      the result of decreased synthesis and release of secondary agonists (TXA(2), ADP)
      in stimulated platelets. It is also possible that sodium selenite blocks the
      release of arachidonic acid from platelet membranes via phospholipases.

PMID- 16801091
TI  - Aspirin increases platelet sensitivity to adenosine diphosphate in patients with
      coronary artery disease.

PMID- 16801092
TI  - Functional and fibrinogen receptor studies in platelets in pre-eclamptic toxaemia
      of pregnancy.
AB  - It is believed that platelets play a key role in the production of pre-eclamptic
      toxaemia and toxaemia of pregnancy. Toxaemia of pregnancy is described as a
      condition of chronic DIC where there is thrombocytopenia as well as raised fibrin
      degradation products. Since fibrinogen receptors are involved in the final stage
      of the platelet aggregation reaction, we wanted to investigate the platelet
      receptors for fibrinogen in normal and abnormal pregnancy. Thirty-six normal
      pregnant women (12 in their 2nd trimester, 24 in their 3rd trimester), 24
      pregnant pre-eclamptic toxaemia cases and 16 non-pregnant controls were included
      in the present study. All patients with pre-eclamptic toxaemia had oedema,
      proteinuria and hypertension. Flow cytometric study of platelets was undertaken
      utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen
      antibody in unstimulated and ADP-stimulated (final concentration 0.02 M)
      platelets. The intensity of platelet fluorescence was classified into three
      groups and expressed in arbitrary units. The results indicate that there are a
      higher number of stimulated platelets expressing fibrinogen receptors in the
      circulation of patients with pre-eclampsia. Thus, it is possible to hypothesize
      that platelets showing increased fibrinogen receptors aggregate and form
      microthrombi in smaller vessels in women with pre-eclamptic toxaemia.

PMID- 16801093
TI  - Docosahexaenoic acid and docosapentanoic acid incorporation into human platelets
      after 24 and 72 hours: inhibitory effects on platelet reactivity.
AB  - Short-term in vitro platelet membrane lipid enrichment studies and feeding trials
      of human subjects with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      have shown a decreased reactivity in the platelet response to collagen. In this
      study, exogenous albumin-bound n-3 polyunsaturated fatty acids (PUFAs), namely
      EPA, DHA and docosapentanoic acid (DPA) were added to platelet suspensions and
      maintained at 22 degrees C for 24 and 72 hours. Subsequently, the aggregation
      response to agonist stimulation and the morphological appearance of the platelets
      were evaluated. A significant enrichment of platelet phospholipids (PL) in n-3
      fatty acids occurred upon incubation with n-3 PUFAs in vitro, which was
      accompanied by a decrease in the aggregation response to collagen and
      preservation of platelet morphology compared with non-supplemented control
      platelet preparations. The inhibitory effect of the n-3 PUFAs appeared to be
      surface mediated in the case of DHA and DPA because the platelet response to
      agonist returned when the fatty acids were removed by washing. The platelet
      aggregation response after storage at 22 degrees C was also evaluated in platelet
      suspensions collected from healthy individuals before and after 42 days of
      dietary supplementation with seal oil, rich in DPA and DHA. Unlike the in vitro
      supplementation, in vivo modification and enrichment of platelet PLs by ingestion
      of seal oil did not appear to improve platelet function during storage relative
      to the placebo group.

PMID- 16801094
TI  - Inhibitory mechanism of human platelet aggregation by nafamostat mesilate.
AB  - We found that nafamostat mesilate (NM) inhibits platelet aggregation induced by
      all agonists tested, including ADP, collagen, arachidonic acid, thromboxane A
      analog, A23187, phorbol 12-myristate 13-acetate (PMA), NaF and thrombin. The IC50
      values were in the range of 9.3-17.8 microM. NM inhibited agonists-induced
      aspirin-treated platelet aggregation at >10 microM, suggesting that the action
      site lies beyond thromboxane (TXA)2 formation. However, NM inhibited thrombin
      (0.5 IU/ml)-induced TXB2 formation (IC50 = 1.9 +/- 0.6 microM, mean +/- SD).
      Intracellular Ca2+ mobilization was also inhibited only when platelets were
      challenged by thrombin, but the effect was found at NM concentrations >50 microM.
      This finding suggests that NM reduces the responses to thrombin by inhibiting its
      proteolytic activity on the platelet thrombin receptor (PAR1). NM did not affect
      the intracellular cAMP concentration or A-kinase activity. Agonists-induced
      surface expression of activated glycoprotein (GP)IIb-IIIa was inhibited by 10
      microM NM and was completely inhibited by 50 microM NM. Since this inhibitory
      effect was parallel to the inhibition of platelet aggregation, the main
      inhibitory mechanism of NM against platelet aggregation seemed to be the
      suppression of activated GPIIb-IIIa expression, which makes it able to bind
      fibrinogen.

PMID- 16801095
TI  - Prevalence of anti-beta(2) glycoprotein-I antibody in patients with primary or
      secondary immune thrombocytopenia.
AB  - We determined the prevalence of antibodies to beta(2) glycoprotein-I (beta(2)
      GPI) in sera of 57 patients with primary or secondary immune thrombocytopenia
      positive for platelet antibody (PAIgG) and in 16 healthy control subjects. Both
      isotypes (IgG and IgM) of anti-beta(2) GPI were detected by means of
      semiquantitative ELISA and platelet antibodies were measured by means of flow
      cytometry using FITC-labeled anti-human IgG. Six (10.5%) of 57 patients with
      immune thrombocytopenia had anti-beta(2) GPI, whereas none of the 16 healthy
      subjects had anti-beta(2) GPI. Four were positive for IgM anti-beta(2) GPI, one
      for IgG anti-beta(2) GPI, and one was positive both for IgM and IgG anti-beta(2)
      GPI. There was no significant association between the presence of anti-beta(2)
      GPI and the severity of thrombocytopenia. Our findings suggest that some patients
      with immune thrombocytopenia have anti-beta(2) GPI in addition to the increased
      PAIgG; however, the results do not support a major role for anti-beta(2) GPI in
      the pathogenesis of immune thrombocytopenia.

PMID- 16801096
TI  - Increased platelet activation in renal transplant patients.
AB  - BACKGROUND: Patients with functioning renal transplants are at risk of graft
      thrombosis in the postoperative period, and of fistula thrombosis and other
      thrombotic events thereafter. Investigation and therapeutic manipulation of
      haemostasis in these patients offers a means to counter this thrombotic tendency.
      METHODS: Platelet aggregation in whole blood, plasma von Willebrand factor and
      plasma fibrinogen levels were measured in 32 stable renal transplant patients
      (creatinine <200 micromol/litre, age of graft >4 months) and in 32 age, sex and
      smoking-habit matched normal controls. RESULTS: In both patient and control
      groups, seven patients were smokers and the remaining 25 were non-smokers. There
      was no significant difference in age between patients and controls [patients,
      median: 39 (20-64) years; controls: 38 (24-60) years]. Spontaneous platelet
      aggregation was significantly higher in the patients at all time points studied
      [30s-6 min; at 4 min: patients median (interquartile range) 19.4 (11.3-27.3)%;
      controls, 8.0 (5.1-15.0)%, P < 0.0005]. ADP-induced aggregation was also
      increased at a concentration range of 0.1-3 microM (at 1 microM, 1 min, patients
      median (interquartile range) was 52.4 (30.5-70.0)%; controls was 16.5 (1.4
      31.4)%, P < 0.0001). Transplant patients had significantly higher von Willebrand
      factor and fibrinogen levels compared with the controls (von Willebrand factor,
      patients median (range): 158 (13-269)%; controls: 85 (43-223)%, P < 0.00001;
      fibrinogen, patients: 3.29 (2.12-7.39) g/litre; controls: 2.81 (1.84-4.65)
      g/litre, P < 0.0002). CONCLUSION: Patients with stable renal transplants have in
      vitro evidence of enhanced platelet activation, and increased plasma von
      Willebrand factor and fibrinogen levels.

PMID- 16801097
TI  - Binding of polymerizing fibrin to integrin alpha(IIb)beta(3) on chymotrypsin
      treated rabbit platelets decreases phosphatidylinositol 4,5-bisphosphate and
      increases cytoskeletal actin.
AB  - Incubation of polymerizing fibrin with washed, chymotrypsin-treated (CT) rabbit
      platelets resulted in the formation of platelet-fibrin clots, a decrease of 27.4%
      (P < 0.001, n = 20) in the amount of phosphatidylinositol 4,5-bisphosphate (PIP)
      and an increase of 37.2% (P < 0.001, n = 20) in phosphatidylinositol 4-phosphate
      (PIP(2)), apparently because of a shift in the equilibria between PIP(2) and PIP
      toward PIP. In contrast, incubation of fibrinogen with CT-platelets resulted in
      agglutination of platelets, but no changes in the phosphoinositides.
      Preincubation of CT-platelets with staurosporine (1 microM) to inhibit protein
      phosphorylation, okadaic acid (1 microM) to inhibit protein phosphatases,
      genistein (100 microM) to inhibit protein tyrosine phosphorylation, PGE (10
      microM) to increase cAMP and cause Ca2+ sequestration or with wortmannin (50 nM)
      to inhibit phosphoinositide 3-kinase, did not inhibit the polymerizing fibrin
      induced decrease in PIP2 and increase in PIP. Preincubation with cytochalasin E
      (CE, 5 microM) inhibited the decrease in PIP(2) by 57% (P < 0.01, n = 8), but not
      completely. CE did not affect the resting levels of PIP2. Thus, the state of the
      actin cytoskeleton appears to affect signalling from the integrin receptor
      alpha(IIb)beta(3) to the enzymes of phosphoinositide interconversion. Platelet
      cytoskeleton actin content increased by 16.4 4.1% (P < 0.01, n = 5) because of
      polymerizing fibrin binding to CT-platelets. This is the first demonstration of a
      pathway involving a decrease in PIP(2) caused by binding of polymerizing fibrin
      to alpha(IIb)beta(3) and an associated increase in cytoskeletal actin, which may
      be involved in reorganization of the cytoskeleton for platelet-mediated clot
      retraction.

PMID- 16801098
TI  - cAMP is an important messenger for ADP-induced platelet aggregation.
AB  - In rat platelets, basal cAMP levels were not changed upon stimulation with ADP
      and it was concluded that cAMP is not an important messenger for ADP-induced
      aggregation (Savi et al., Blood Coagul Fibrinolysis, 1996; 7: 249-52). In the
      present study, the effects of prostaglandin E(1) (PGE(1)) and ADP on human
      platelet aggregation, cAMP generation and VASP phosphorylation were studied.
      Phosphorylation of the protein kinase A (PKA) substrate VASP and inhibition of
      platelet aggregation by PGE(1) occurred without measurable changes in cellular
      cAMP levels. In addition, a marked inhibition of basal VASP phosphorylation by
      ADP was observed. It is concluded that cAMP determinations do not necessarily
      detect a possible activation or inhibition of the cAMPPKA pathway in platelets.
      Thus, cAMP might well be an important second messenger for ADP-induced platelet
      aggregation.

PMID- 16801099
TI  - Platelet glycosomes.
AB  - Most of the structural constituents of human platelets have been well
      characterized in ultrastructural studies over the past five decades. However,
      some structures occur rarely and have not been reported previously. The present
      article describes an organelle bounded by a unit membrane and filled with
      particles of glycogen. For that reason we have called this organelle the
      'glycosome'. Similarities and differences between glycosomes, alpha-granules and
      tubular inclusions are discussed.

PMID- 16801100
TI  - Response of blood platelets to resveratrol.
AB  - The phytochemical resveratrol (3,4',5-trihydroxystilbene), which is found in
      grapes and wine, has been reported to have a variety of anti-inflammatory, anti
      platelet and anti-carcinogenic effects. The aim of the present study was to
      evaluate the effects of trans-resveratrol on adhesion of blood platelets to
      collagen, as well as on thrombininduced platelet aggregation and
      malonyldialdehyde (MDA) production in vitro. Pretreatment of platelets with
      resveratrol (50 microg/ml) inhibited their adhesion to collagen (by 32% in
      resting platelets and by 57% in thrombin-activated platelets after 1 h of
      preincubation) and thrombin-induced platelet aggregation (by 59% after 30 min
      preincubation). Resveratrol also had an inhibitory effect on the generation of
      malonyldialdehyde (a marker of thromboxane A(2) synthesis) measured as
      thiobarbituric reactive substance in thrombin-activated platelets.

PMID- 16801101
TI  - The generation of the F(2)-isoprostane 8-epi-PGF(2alpha) by human platelets on
      collagen stimulation.
AB  - F(2)-isoprostanes are prostaglandin (PG) F(2)-like compounds formed via non
      enzymatic peroxidation of arachidonic acid, although some F(2)-isoprostane
      production may be cyclo-oxygenase (COX)-mediated. Of these substances 8-epi
      prostaglandin F(2)alpha (8-epi-PGF(2alpha)) has received the most attention as it
      induces vasoconstriction and mitogenesis, and influences pathophysiological
      mechanisms relevant to arterial disease. Using improved methods for F(2)
      isoprostane determination we examined collagen-stimulated platelet production of
      F(2)-isoprostanes in platelet-rich plasma (PRP), distinguishing between the free
      and esterified forms of these substances. Collagen stimulation caused marked
      release to the plasma (platelet-poor; PPP) of free 8-epi-PGF(2alpha) (2 +/- 2
      pg/mg platelet protein vs 174 +/- 53 pg/mg protein, control (i.e. non-stimulated)
      vs collagen-stimulated, P < 0.05) and of free 9alpha ,11alpha-PGF (37 +/- 19
      pg/mg protein vs 1948 +/- 643 pg/mg protein, control vs stimulated, P < 0.05), a
      COX derived product. Neither free nor esterified 9alpha, 11beta-PGF and 9beta,
      11alpha-PGF(2alpha) were detectable in control or collagen stimulated samples.
      Sample concentrations of the esters of 8-epi-PGF(2alpha) and 9alpha, 11alpha
      PGF(2alpha) were unaltered by collagen stimulation. These data confirm a previous
      report that activated platelets release the F2-isoprostane 8-epi-PGF(2alpha),
      accompanying the release of a COX-derived product, 9alpha, 11alpha-PGF(2alpha).

PMID- 16801103
TI  - Platelets and lipoprotein (a): a brief overview of their role in the pathogenesis
      of atherothrombosis.
AB  - The relationship between lipids and the haemostatic mechanisms participating in
      the evolution of the atherosclerotic plaque have been undergoing extensive
      investigation for over a century. Circulating lipoproteins can enhance platelet
      activity. Among these lipid fractions, lipoprotein (a) (Lp(a)), a predictor of
      atherosclerotic disease, has been proposed as a link between lipids and
      haemostasis. In this review, we briefly consider lipid-platelet, and particularly
      Lp(a)-platelet, interactions which may be relevant to the pathogenesis of
      atherosclerotic disease and its complications.

PMID- 16801104
TI  - Blockade of GpIIb/IIIa inhibits the release of vascular endothelial growth factor
      (VEGF) from tumor cell-activated platelets and experimental metastasis.
AB  - Evidence that platelets play a role in tumor metastasis includes the observation
      of circulating tumor cell-platelet aggregates and the anti-metastatic effect of
      thrombocytopenia and anti-platelet drugs. Platelets have recently been shown to
      contain vascular endothelial growth factor (VEGF) which is released during
      clotting. We therefore studied the effects of (1) tumor cell-platelet adherence
      and tumor cell TF activity on platelet VEGF release; and (2) the effects of
      GpIIb/IIIa blockade on tumor cell-induced platelet VEGF release, tumor cell
      induced thrombocytopenia and experimental metastasis. Adherent A375 human
      melanoma cells (TF+) and KG1 myeloid leukemia (TF-) cells were cultured in RPMI
      containing 10% fetal bovine serum. Platelet-rich plasma was obtained from normal
      citrated whole blood and the presence of VEGF (34 and 44 kDa isoforms) confirmed
      by immunoblotting. Platelet-rich plasma with or without anti-GpIIb/IIIa
      (Abciximab) was added to A375 monolayers and supernatant VEGF measured by ELISA.
      Tumor cell-induced platelet activation and release were determined by CD62P
      expression and serotonin release respectively. In vitro, tumor cell-platelet
      adherence was evaluated by flow cytometry. In vivo, thrombocytopenia and lung
      seeding were assessed 30 min and 18 days, respectively, after i.v. injection of
      Lewis Lung carcinoma (LL2) cells into control or murine 7E3 F(ab')(2) (6 mg/ kg)
      athymic rats. Maximal in vitro platelet activation (72% serotonin release)
      occurred 30 min after adding platelets to tumor cells. At this time, 87% of the
      A375 cells had adhered to platelets. Abciximab significantly (P<0.05) reduced
      platelet adherence to tumor cells as evidenced by flow cytometry. Incubation of
      A375 cells with platelets induced VEGF release in a time-dependent manner. This
      release was significantly inhibited by Abciximab (81% at 30 min; P<0.05). In the
      presence of fibrinogen and FII, VEGF release induced by A375 (TF+) cells was
      significantly higher than that induced by KG1 (TF-) cells (105.5+/-24 vs. 42+/-7
      pg/ml; P<0.001). Omitting fibrinogen or FII from the reaction mixture markedly
      decreased VEGF release. In vivo, GpIIb/IIIa blockade with murine 7E3 F(ab')(2)
      reduced LL2 tumor cell-induced thrombocytopenia by 90% (P<0.001) and lung seeding
      by 82% (P<0.05). We conclude that TF-bearing tumor cells can activate platelets
      largely via thrombin generation, and that such activation is associated with
      release of VEGF. This may enhance metastasis, possibly by increasing
      extravasation at points of adhesion to vascular endothelium.

PMID- 16801105
TI  - Evaluation of angiographic contrast media and platelet function with impedance
      aggregometry and the PFA-100 'platelet function analyser'.
AB  - BACKGROUND: Angiographic contrast media are used in balloon angioplasty and may
      influence thrombotic complications of the procedure. We studied the effect of
      different media on platelet aggregation in whole blood using impedance
      aggregometry and the PFA-100 'platelet function analyser' (Dade, USA). METHODS:
      Venous blood samples from 18 healthy volunteers were split into four aliquots and
      mixed with 10% normal saline control, non-ionic medium (iohexol), low-molecular
      weight ionic medium (ioxaglate) and high-molecular weight ionic medium
      (diatrizoate). Samples were studied with impedance aggregometry and the PFA-100.
      RESULTS: All media caused significant inhibition of aggregation compared with
      control with both methods (P<0.001). Antiplatelet potency was greatest with
      diatrizoate, intermediate with ioxaglate and least with iohexol with both methods
      (P<0.01). Electron microscopy of the PFA-100 membrane demonstrated occlusion of
      the experimental aperture with platelet thrombus in the control. Inhibition of
      platelet thrombus was seen with all media, greatest with diatrizoate,
      intermediate with ioxaglate and least with iohexol. CONCLUSIONS: The media
      studied significantly inhibited platelet aggregation in vitro and potency was
      greater with ionic than non-ionic media. These methods use a combination of shear
      and chemical agonist with whole blood and may reproduce in vivo arterial
      conditions better than other techniques.

PMID- 16801106
TI  - Inhibitory effect of Ginkgo biloba extract on human platelet aggregation.
AB  - The effect of pure flavonoids and Gingko biloba extract (GBE) on human platelet
      aggregation was investigated. Most of the flavonoids and vitamin E did not affect
      platelet aggregation in platelet-rich plasma (PRP); however some of these
      flavonoids inhibited platelet aggregation in gel-filtered platelets (GFP). GBE
      inhibited both ADP- and collagen-induced platelet aggregation in PRP, GFP and in
      whole blood in a dose-dependent manner. GBE at very low concentrations inhibited
      whole blood aggregation induced by ADP compared with those used for PRP or GFP.
      Flavonoids and GBE decreased the production of TxA(2) induced by collagen and ADP
      in PRP. However, no correlation was observed between the inhibition of platelet
      aggregation and the decrease of TxA(2) synthesis. GBE and flavonoids did not
      affect platelet membrane fluidity. However, the incubation of PRP with GBE
      increased cAMP levels in platelets, which is known to inhibit platelet activation
      by lowering intracellular Ca2+ levels. GBE is a mixture of many compounds,
      including flavonoids and gingkoglides, which affect metabolism of cAMP, TxA(2)
      and Ca2+ in platelets. It is effective in the inhibition of platelet aggregation,
      both in PRP and whole blood, and thus may be potentially used as an effective
      oral anti-platelet therapeutic agent.

PMID- 16801107
TI  - Suppression of aggregation and calcium mobilisation in bovine platelets by
      external magnesium.
AB  - We have examined the effect of increasing external Mg2+ and removing external
      Ca2+ on bovine platelet activation (measured by time taken for OD to recover to
      basal following shape change) and thrombin-induced Ca2+ transients. Increasing
      Mg2+ prolonged the duration of the recovery, both with and without external Ca2+,
      whereas Mg2+ removal shortened this parameter. In resting platelets, increasing
      external Mg2+ to 2.5 mM or above reduced basal [Ca2+](i), but had no significant
      effect when external Ca2+ was removed. Increasing external Mg2+ altered the time
      course of the thrombin-induced rise in [Ca2+](i) with or without [Ca2+](o). There
      was no significant change in OD in a platelet suspension exposed to the highest
      dose (20 mM) of [Mg2+](o), indicating that the observed effects were not
      accompanied by significant changes in cell volume. These results suggest that (a)
      the effect of Mg2+ on bovine platelet function and Ca2+ mobilisation occurs
      through Ca2+-dependent and Ca2+-independent mechanisms, and (b) significant
      aggregation can occur in bovine platelets even in the absence of external Ca2+.

PMID- 16801108
TI  - Unexpected changes in the catecholamine content of platelets and plasma during
      exercise.
AB  - Catecholamines are retained within platelets for several hours after plasma
      catecholamine concentrations have returned to baseline. To determine whether
      platelet catecholamine concentrations may provide an index of short-term
      elevations in plasma adrenaline (A) and noradrenaline (NA), the response of
      plasma and platelet catecholamines to an interval supramaximal, Max (107% VO(2)
      Max), and submaximal, Submax (37% VO(2) Max), cycling protocol was examined in
      seven healthy male volunteers, 22-34 years. Despite large rises in plasma NA and
      A in the Max study (12- and 8-fold increases above baseline, respectively) and
      smaller rises in the Submax study, the baseline platelet concentrations of A and
      NA fell significantly in the first 15 min of exercise in both groups. This fall
      was greater in the SubMax protocol. Catecholamine concentrations then increased
      slowly in the second half of exercise, but never returned to baseline. The
      circulating platelet count almost doubled during the exercise period, increasing
      from 308 to 569 X 10(3) platelets/ml plasma in both studies, returning close to
      baseline in recovery. These results indicate that at the beginning of exercise
      there is large rise in plasma catecholamines and the circulating platelet count,
      with a fall in the platelet catecholamine concentrations. This suggests that a
      sequestered platelet population, free of catecholamines, is released at the
      beginning of exercise. This release most probably occurs from the spleen. If this
      is the case, the reason for a propagation of platelets in the spleen, free of
      catecholamines, requires further investigation.

PMID- 16801109
TI  - Generation of platelet-derived microparticles and procoagulant activity by
      heparin-induced thrombocytopenia IgG/serum and other IgG platelet agonists: a
      comparison with standard platelet agonists.
AB  - Heparin-induced thrombocytopenia (HIT) is a relatively common, immunoglobulin
      mediated adverse drug reaction associated with in vivo thrombin generation and
      both venous and arterial thrombosis. Serum and purified IgG from patients with
      HIT induce normal platelets to generate procoagulant platelet-derived
      microparticles, but the magnitude of this response in comparison with other IgG
      and standard platelet agonists is unknown. We describe a comparison of IgG
      platelet agonists, including HIT-IgG/serum, heat-aggregated IgG, and platelet
      activating murine monoclonal antibodies, with standard 'strong' and 'weak'
      platelet agonists, and have determined their relative ability to generate
      platelet procoagulant activity. Using washed normal platelets as targets, we
      observed that HIT sera as well as other IgG agonists produced similar or even
      greater numbers of microparticles and procoagulant activity than the standard
      strong platelet agonists (thrombin, collagen, and thrombin receptor agonist
      peptide). The only exception was the non-physiological platelet agonist, calcium
      ionophore, which consistently produced a platelet procoagulant response even
      greater than the IgG agonists. We conclude that the IgG class of platelet
      agonists (including pathogenic HIT antibodies) is an effective trigger of the
      platelet procoagulant response comparable at least to strong physiological
      platelet agonists. These results help to explain the association between HIT, in
      vivo thrombin generation, and thrombosis.

PMID- 16801110
TI  - EDTA induced changes in platelet structure and function: influence on particle
      uptake.
AB  - Ethylenediaminetetraacetic acid (EDTA) causes structural, biochemical and
      functional damage to blood platelets. The alterations induced are considered
      irreversible. However, the degree of irreversibility, and whether all functions
      are similarly compromised by EDTA have not been fully evaluated. The present
      study has examined platelets treated with EDTA to produce the structural changes
      in channels of the open canalicular system (OCS) associated with irreversible
      dissociation of the fibrinogen receptor, GPIIb-IIIa (alpha(IIb)beta(3)), for
      their ability to interact with particulates in suspension. Despite severe
      narrowing and near occlusion of peripherally oriented OCS channels by EDTA,
      treated cells were able to bind, translocate and take up fibrinogen-coated gold
      particles (Fgn/Au), colloidal gold and latex spheres. Thus exposure to EDTA may
      compromise some aspects of platelet function, but not others which may be
      important for participation in hemostatic events.

PMID- 16801111
TI  - Some characteristics of platelet concentrates contaminated with Staphylococcus
      epidermidis.
AB  - The study investigates platelet concentrates (PCs) contaminated with
      Staphylococcus epidermidis. The work was conducted using 12 pairs of PCs. Light
      transmission through the PCs was observed over 7 days. Immediately after
      preparation, one PC was inoculated with Staphylococcus epidermidis (17-43 colony
      forming units (CFU)/ ml) and the other served as a non-contaminated control. In
      the contaminated PCs the CFU/ml and swirling were determined on days 1, 3 and 7.
      In all PCs determination of pH and the extent of shape change (ESC) was carried
      out on days 3 and 7. All contaminated PCs had visible swirling on day 3 but they
      contained 2.0 X 10 4 to 9.0 X 10 8 CFU/ml. pH (P=0.05) and ESC (P<0.05) then were
      slightly lower. On day 7, eight of 12 of the contaminated PCs failed to display
      transmission changes despite deranged analytical results and impaired swirling.
      During early storage the contaminated units had unimpaired swirling and only
      slightly impaired in vitro quality. They appear to be difficult to identify in
      the routine.

PMID- 16801112
TI  - Platelet aggregation in atopic dermatitis.
AB  - Many observations suggest the active role of platelets in allergic inflammation.
      However, this problem is poorly researched in atopic dermatitis. The aim of study
      was to examine the intensity and velocity of platelet aggregation and a potential
      relationship with some immunological parameters (total IgE and specific-IgE serum
      levels) in atopic dermatitis patients. Platelet aggregation was evaluated in 12
      subjects with atopic dermatitis and 12 healthy, nonatopic persons, according to
      the Born method, in a dual-channel aggregometer, in response to three exogenous
      stimulators (ADP, thrombin and collagen). The intensity and velocity of platelet
      aggregation and total platelet counts did not differ between the two groups
      irrespective of the type of extrinsic stimulator used. In contrast to other
      atopic diseases, in atopic dermatitis platelet aggregation is not impaired.

PMID- 16801113
TI  - Effects of copper-aspirin complex on plasma 6-keto-prostaglandin F(1alpha) level
      and platelet cytosolic calcium in rabbits.
AB  - Effects of copper-aspirin complex on washed platelet aggregation, thromboxane
      B(2) formation and 6-ketoprostaglandin F(1alpha) level were monitored by Born's
      and Terashita's methods, respectively. The influence of copper-aspirin complex on
      cytosolic free calcium was examined using the fluorescent indicator, Fura 2-AM.
      Copper-aspirin complex significantly inhibited arachidonic acid-induced
      aggregation in washed platelets. The IC(50) value was 9.6 micromol L(-1). Copper
      aspirin complex significantly decreased arachidonic acid-induced thromboxane B(2)
      formation by 87.1% in washed platelets. Ten mg kg(-1) of copper-aspirin complex
      given intragastrically markedly increased the plasma level of 6-keto
      prostaglandin F(1alpha). Aspirin, however, reduced both thromboxane B(2)
      formation and 6-keto-prostaglandin F(1alpha) level. In the presence of CaCl2 1
      mmol L(-1), copper-aspirin complex (20, 40 and 80 micromol L(-1)) markedly
      lowered arachidonic acid-induced increase in platelet calcium from the resting
      level (270+/-36 nmol L(-1)) to 213+/-14, 170+/-20 and 135+/-17 nmol L(-1),
      respectively. In the presence of ethylene glycol-bis (beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid 1 mmol L(-1), copper-aspirin complex (20, 40 and 80
      micromol l L(-1)) significantly suppressed the release of intracellular calcium
      induced by arachidonic acid from 127+/-23 nmol L-1 to 108+/-17, 93+/-12 and 70+/
      13 nmol L(-1).

PMID- 16801114
TI  - Aspirin increases platelet sensitivity to adenosine diphosphate in patients with
      coronary artery disease.

PMID- 16801115
TI  - Platelet function and lipid-lowering interventions.
AB  - Platelets play an important role in the process of atherothrombosis, and
      antiplatelet therapy is of proven efficacy in the prevention of vascular events
      in high-risk patients. In this review, we briefly consider the studies reporting
      that circulating atherogenic lipoproteins enhance platelet activity. We also
      evaluate the evidence showing that lipid-lowering interventions (including the
      use of statins) are associated with the normalisation of platelet activity. This
      beneficial effect should enhance the anti-atherogenic and anti-thrombotic
      potential of lipid-lowering interventions.

PMID- 16801116
TI  - Platelet membrane interactions.
AB  - The term 'viscous metamorphosis' was coined in early studies to describe the
      fusion and disintegration of platelets into an amorphous mass sealing sites of
      vascular injury. Improvements in morphological techniques revealed that
      disintegration was not involved in the platelet hemostatic reaction, and that
      part of the definition was eliminated. Fusion was retained, however, even though
      platelet fusion was never observed. The present study has examined the different
      forms of platelet membrane interaction to determine if fusion is an appropriate
      term for any aspect of platelet physiology or pathology. Fusion was not observed
      during platelet-platelet, platelet-surface or platelet-fibrin interaction at any
      stage in the development. Only fusion of secretory organelles with channels of
      the open canalicular system (OCS) during the release reaction represents
      involvement of the phenomenon. Pathological fusion occurs during long-term
      storage when alpha granules bind together to form giant organelles. The only
      examples of surface membrane fusion develops when platelets are incubated with
      the cholinergic agent, carbachol (carbamyl choline chloride). Ethylenediamine
      tetraacetic acid also causes intimate associations of OCS channels and
      interacting surface membranes, but not the fusion of lipid bilayers that
      carbachol induces. Thus, fusion does not appear to be an appropriate term to
      describe platelet-membrane interactions, except for the process of secretion.

PMID- 16801117
TI  - Inhalation of nitric oxide inhibits ADP-induced platelet aggregation and alpha
      granule release.
AB  - To gather further information about the effects on blood platelet activation of
      in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood
      from healthy, non-smoking male volunteers before and after 30 min inhalation of
      40 ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or
      thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non
      anticoagulated blood was exposed to immobilised collagen at arterial blood flow
      conditions (2600 s(-1)). Blood samples from both the in vitro and ex vivo
      experiments were stained with fluorochrome-labelled Annexin-V and antibodies
      against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three
      colour flow cytometry technique. NO inhalation reduced the platelet activation
      response to adenosine diphosphate (ADP) stimulation by decreasing platelet
      platelet aggregation, alpha-granule release and platelet-leukocyte conjugate
      formation. TRAP-stimulated platelet activation, collagen-induced platelet
      activation and thrombus growth was unaffected by NO inhalation. We therefore
      suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the
      newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results
      demonstrate that blood platelet activation in healthy subjects is modulated by
      inhalation of NO in therapeutically relevant doses, although the clinical impact
      of our findings remains unclear.

PMID- 16801118
TI  - Decreased arachidonic acid liberation participates in the anti-aggregatory effect
      of the histamine H(1)-receptor antagonist Bromadryl.
AB  - The in vitro effect of the histamine H(1)-receptor antagonist Bromadryl on
      aggregation of human blood platelets was studied. Bromadryl inhibited stimulated
      platelet aggregation in a dose-dependent way. Depending on the aggregation
      stimulus used, its mean inhibitory concentrations were 16 micromol/litre
      (thrombin), 18 micro mol/litre (A23187), 92 micromol/litre (adrenaline) and 395
      micromol/litre (adenosine diphosphate). The inhibitory effect was most pronounced
      in aggregation stimulated with phorbol 12-myristate 13-acetate (IC(50) = 3
      micromol/litre), suggesting interference of Bromadryl with protein kinase C
      activity. In Bromadryl-treated platelets, a very good correlation was found
      between aggregation and liberation of arachidonic acid; the correlation
      coefficients calculated for thrombin- and A23187-stimulated platelets were
      0.94123 and 0.98611, respectively. This indicates that interaction of Bromadryl
      with phospholipase A(2) (an enzyme liberating arachidonic acid) may be involved
      in the anti-aggregatory effect. However, in platelets stimulated with thrombin,
      thromboxane formation was decreased at a lower mean inhibitory concentration of
      Bromadryl (6 micromol/litre) than arachidonic acid liberation (72
      micromol/litre); thus, phospholipase A(2) does not seem to be the only site in
      the arachidonate metabolism cascade affected by Bromadryl. Although specific
      interference of Bromadryl with histamine receptors could not be excluded,
      alterations in platelet membrane structure and functions are supposed to be
      principal in the anti-aggregatory effect of Bromadryl.

PMID- 16801119
TI  - The P2Y1 receptor is essential for ADP-induced shape change and aggregation in
      mouse platelets.
AB  - Adenosine diphosphate (ADP) is an important platelet agonist, causing the shape
      change and aggregation required for physiological hemostasis. We have recently
      demonstrated that the P2Y1 receptor plays an important role in ADP-induced shape
      change and aggregation in human platelets. The role of the P2Y1 receptor in these
      physiological responses can be conclusively delineated with gene-knockout
      approaches in transgenic mice. However, before proceeding to the P2Y1 gene
      knockout mice generation, it is important to demonstrate that the P2Y1 receptor
      plays an essential role in ADP-induced shape change and aggregation in mouse
      platelets. We examined platelets pooled from twenty 129J mice, a strain used in
      the generation of knockout mice. Immunofluorescence experiments using P2Y1
      specific antiserum detected the presence of the P2Y1 receptor on mouse platelets.
      ARL 66096, a potent P2T(AC) receptor antagonist, caused a dose-dependent
      inhibition of both ADP-induced aggregation and ADP-induced inhibition of adenylyl
      cyclase, without affecting shape change or calcium mobilization. On the other
      hand, adenosine-2'-phosphate-5'-phosphate (A2P5P), a P2Y1 receptor-selective
      antagonist, caused a dose-dependent inhibition of ADP-induced aggregation and
      shape change, as well as inhibiting the mobilization of calcium from
      intracellular stores. A2P5P had no effect on the inhibition of adenylyl cyclase
      by ADP. These findings clearly demonstrate the existence of two distinct ADP
      receptors, the P2Y1 and P2T(AC), in mouse platelets with similar function as in
      human platelets.

PMID- 16801120
TI  - ATP does not affect fibrinogen binding to platelet GPIIbIIIa in systems free of
      signal transduction.
AB  - Recent studies have suggested that the platelet fibrinogen (Fg) receptor,
      platelet membrane glycoprotein IIbIIIa (GPIIbIIIa, or integrin alpha(IIb)beta(3))
      is also an adenosine triphosphate (ATP) binding site, and that the binding of ATP
      can directly inhibit the Fg-binding function of GPIIbIIIa. However, any direct
      effect of ATP on GPIIbIIIa function in intact fresh platelets is difficult to
      distinguish from indirect inhibitory effects via competition with ADP or
      elevation of platelet cyclic AMP levels. We therefore studied effects of ATP on
      Fg binding to activated GPIIbIIIa on the following model particles: externally
      activated and fixed platelets, as well as latex particles and liposomes
      containing functionally competent activated GPIIbIIIa receptors for Fg. These
      particles have 'normal', activated GPIIbIIIa in terms of: (1) binding affinity,
      (2) specificity to Fg, and (3) conformational change(s) after Fg binding. These
      particles neither require nor respond to further activation in order to bind Fg.
      With these model particles, we showed that ATP does not have any direct effect on
      the binding of Fg to platelet GPIIbIIIa and platelet aggregation. These
      simplified model particles are useful tools in the mechanistic study of platelet
      GPIIbIIIa function and the interaction between platelet GPIIbIIIa and its
      ligands.

PMID- 16801121
TI  - Role of tyrosine phosphorylation in regulation of inositol 1,4,5-trisphosphate
      mediated Ca2+ release in human platelets.
AB  - Thrombin activation of human platelets is accompanied by tyrosine phosphorylation
      of many cellular proteins, as well as changes in the cytosolic Ca2+
      concentration. Consequently, we assessed tyrosine phosphorylation of the platelet
      inositol 1,4,5-trisphosphate receptor (IP(3)R) to determine if phosphorylation
      modulates Ca2+ release from internal stores. Stimulation of platelets with
      thrombin resulted in tyrosine phosphorylation of the type 1 IP(3)R, which peaked
      at 3 min followed by dephosphorylation to the basal level by 10 min. Thrombin
      also increased the extent of IP(3)R-mediated Ca2+ release 1.6-fold in crude
      platelet membranes isolated from thrombin-stimulated (3 min) platelets. Since we
      have previously shown that the plasma membrane Ca2+-ATPase (PMCA) is also
      phosphorylated on tyrosine residues during thrombin-stimulated platelet
      activation, resulting in inhibition of the pump (Dean et al., J Biol Chem 1997;
      272: 15113-9), the present results suggest that early in thrombin-stimulated
      platelet activation, tyrosine phosphorylation of PMCA and IP(3)R results in
      transient enhancement in platelet cytosolic Ca2+, but that this enhancement is
      attenuated by subsequent dephosphorylation.

PMID- 16801122
TI  - International symposium on enhancing the effectiveness of alcohol ignition
      interlock programs.

PMID- 16801123
TI  - The alcohol interlock: an underutilized resource for predicting and controlling
      drunk drivers.
AB  - This report summarizes evidence presented during the Third Annual Ignition
      Interlock Symposium at Vero Beach, Florida, 29 October 2002. The ignition
      interlock prevents a car from starting when blood alcohol concentration (BAC) is
      elevated. We review some of our prior work as well as introduce previously
      unpublished results to demonstrate the manner in which the data recorded by the
      alcohol ignition interlock device can serve as an advance predictor of future
      driving under the influence (DUI) of alcohol risks. Data used in this current
      report represent approximately 2,200 ignition interlock users from Alberta,
      Canada, and about 8,000 interlock users from Quebec, Canada; the Alberta data set
      contained 5.5 million breath tests and the Quebec data 18.8 million breath tests.
      All tests are time and date stamped and this information was used to characterize
      patterns of BAC and vehicle use, and the relationship between BAC elevations and
      DUI offenses that accumulated after the interlock was removed from the vehicles.
      Findings from Cox regression (Marques et al., 2003) show that BAC elevations >
      .02-.04% are more potent predictors of repeat DUI (p < .0001) than even prior DUI
      (p < .006), usually found to be the strongest indicator of driver risk. Prior DUI
      obviously has no use for scaling the risk of first-time offenders. Drivers who
      are both multiple offenders and who have more than a few elevated interlock BAC
      tests are much more likely to repeat DUI. The timing and pattern of elevated BAC
      tests provided during the time drivers were required to use an alcohol ignition
      interlock device are remarkably similar on both a daily basis and an hourly basis
      when the interlock programs from the two provinces are compared directly. Both
      provinces had higher rates of elevated tests on Saturday and Sunday, and the
      fewest elevated tests on Tuesdays. The absolute rate of elevated tests is similar
      despite the two provinces adhering to different interlock lockout points (.02%
      Quebec; .04% Alberta). Charts tracking the Monday-Friday timing of elevated BAC
      tests by hour are nearly identical for both provinces. The most elevated BAC
      tests occurred between 7 and 9 A.M. Monday to Friday, even though most vehicle
      start attempts occurred much later in the day. This higher rate of elevated
      morning BAC likely represents drinking from the prior evening with alcohol not
      yet cleared from circulation; those with elevated BAC in the early morning were
      more likely to have a repeat offense even after accounting for prior DUI and the
      higher overall rate of elevated BAC tests. This is viewed as evidence of a
      drinking problem that will lead to impaired driving after the controlling
      function of the interlock is removed. Policy changes are discussed that might
      take better advantage of interlock information to improve the public response to
      drunk driving.

PMID- 16801124
TI  - Barriers to interlock implementation.
AB  - This commentary reviews current and past vehicle interlock programs for impaired
      driving offenders with a focus on the challenges that courts and motor vehicle
      departments face in attempting to implement mandatory programs as required by
      current federal legislation. There are few offenders in interlock programs
      compared to the large number of impaired drivers arrested each year. This
      suggests that, to increase participation, courts will have to threaten more
      severe sanctions for those offenders who reject interlock programs. A combination
      of electronic house arrest with interlock programs is suggested as a method of
      maximizing interlock use.

PMID- 16801125
TI  - An evaluation of the Swedish ignition interlock program.
AB  - The Swedish alcohol ignition interlock program for driving while intoxicated
      (DWI) offenders, both first-time as well as multiple offenders, was launched as a
      pilot project in 1999. It is a volunteer program and differs in some respects
      from other programs: It covers a period of 2 years, it includes very strict
      medical regulations entailing regular checkups by a physician, it does not
      require a prior period of hard suspension, and it focuses strongly on changes in
      alcohol habits. Records from the 5 years prior to the offence showed that DWI
      offenders are generally in a high-risk category long before their offense, with a
      four to five times higher accident rate (road accidents reported by the police)
      and a three to four times higher rate of hospitalization due to a road accident.
      Only 12% of the eligible DWI offenders took part in the program and, of these,
      60% could be diagnosed as alcohol dependent or alcohol abusers. During the
      program, alcohol consumption is monitored through self-esteem questionnaires
      (AUDIT) and five different biological markers. Our data show a noticeable
      reduction in alcohol consumption among the interlock users. This, combined with
      the high rate of compliance with the regulations, probably accounts for the fact
      that there was no case of recidivism during the program. Preliminary findings
      also suggest a reduction in the annual accident rate for interlock users while in
      the program. It still is too early to draw any conclusions concerning the rate of
      recidivism after completion of the program due to an insufficient amount of data
      for analysis. Nevertheless, the preliminary results are so promising that the
      program will now be expanded to cover all of Sweden as well as to include all
      driver's license categories.

PMID- 16801126
TI  - The impact of mandatory versus voluntary participation in the Alberta ignition
      interlock program.
AB  - Research has demonstrated that participation in an interlock program
      significantly reduces the likelihood of subsequent driving while intoxicated
      (DWI) convictions at least so long as the interlock device is installed in the
      vehicle. Despite the growing number of jurisdictions that allow interlock
      programs and the demonstrated success of these programs, the proportion of DWI
      offenders who actually have the device installed is minimal. In an effort to
      increase the proportion of offenders using interlocks, some jurisdictions require
      offenders to install an interlock as a condition of license reinstatement whereas
      others merely offer offenders a reduction in the period of hard suspension if
      they voluntarily participate in an interlock program. The objective of the
      present study was to determine the extent to which voluntary interlock
      participants are more or less successful in terms of subsequent recidivism than
      those for whom interlock program participation has been mandated. The issue was
      addressed using data from the interlock program in Alberta, Canada, which
      provides for both mandatory and voluntary participation. The recidivism
      experience of voluntary and mandatory interlock participants was examined both
      during and after the period of interlock installation. Cox regression revealed
      that, after controlling for (or equating) the number of prior DWI offenses, the
      survival rates of DWI offenders who were ordered to participate in the interlock
      program did not differ from those of voluntary participants. These results
      suggest that further use of mandatory interlock programs should be just as
      successful as voluntary programs when offenders share characteristics with those
      studied in Alberta.

PMID- 16801127
TI  - Breath alcohol ignition interlock devices: controlling the recidivist.
AB  - This study compares the recidivism rates of two groups of Illinois drivers who
      had their driver's licenses revoked for alcohol-impaired driving and who received
      restricted driving permits. Drivers in both groups had more than two driving
      under the influence (DUI) actions against their record within 5 years or were
      classed as level III alcohol dependents. Drivers in one group were required to
      install breath alcohol ignition interlock devices in their vehicles and drivers
      in the other group were not. The research found that drivers with the interlock
      were one-fifth as likely to be arrested for DUI during the 1 year the device was
      installed as the comparison group, which did not have the device. However, once
      the ignition interlock was removed, drivers in this group rapidly returned to DUI
      arrest rates similar to those in the comparison group. These findings echo
      previous literature. Additionally, the study showed that this voluntary program
      in Illinois reached only 16% of the drivers who met the requirements for
      installing the interlock device. Finally, this study found that individuals who
      were removed from the interlock program and returned to revoked status continued
      to drive. Within 3 years, approximately 50% of this latter group were involved in
      a crash or were arrested for DUI or with an invalid driver's license. Conclusions
      drawn from the study suggest that the breath alcohol ignition interlock device is
      effective in preventing continued driving while impaired. However, the large
      scale effectiveness of the device is limited since most of the drivers eligible
      for the device do not have it installed. To have a significant impact, the
      interlock device must represent a better alternative to drivers whose licenses
      were suspended or revoked because of alcohol arrests compared to remaining on
      revoked status without having the device installed. Finally the research suggests
      that, given the rapid return to predevice recidivism, the devices should remain
      installed until drivers can demonstrate an extended period of being alcohol free.

PMID- 16801128
TI  - Preventing alcohol crashes: the role of ignition interlocks.

PMID- 16801129
TI  - Stromal cells selectively reduce the growth advantage of human committed CD34+
      hematopoietic cells ectopically expressing HOXB4.
AB  - Key players in self-renewal of hemopoietic stem cells are homeobox (HOX)
      transcription factors. In murine cells, overexpression of HOXB4 results in
      expansion of hematopoietic stem- and committed progenitor cells in vitro without
      obvious hematopoietic alterations. In vivo, HOXB4 induced HSC expansion continued
      until stem cell regeneration reached pretransplantation levels. HOXB4 is thus an
      attractive candidate for amplification of stem cells provided that human HOXB4
      overexpressing cells can also be restricted to normal growth in vivo. The stromal
      microenvironment provides the regulatory mechanisms controlling the balance of
      stem cell self-renewal and differentiation. Here, we compared the response of
      HOXB4- and GFP-control vector transduced human CD34(+) cells to stroma encoded
      signals in vitro. In serum-sustained cocultures MS-5 stroma contact reduced the
      output of late CD34- HOXB4(+) cells in relation to GFP-controls 9-fold whereas
      the expansion of early CD34(+)HOXB4(+) cells remained unchanged as compared to
      liquid cultures. In presence of insulin HOXB4 overexpressing cells do not react
      to stroma encoded growth-restricting signals. Our results show that ectopic
      expression of HOXB4 in combination with MS-5 stroma exerts different effects in
      early and late human cord blood CD34(+) cells resulting in an enhanced
      proliferation of early CD34(+) cells in absence or presence of MS-5 stroma and an
      impaired output of late committed CD34(+) cells on MS-5 stroma.

PMID- 16801130
TI  - Implication of stem cell factor in human liver regeneration after transplantation
      and resection.
AB  - The stem cell factor (SCF), besides regulating hemopoietic stem cells homing and
      proliferation, has proliferative effects on hepatocytes and may be involved in
      liver regeneration. We investigate if liver transplantation (LT) and hepatic
      resection (HR) modify the concentration of soluble SCF (s-SCF) in peripheral
      blood of 15 LT and 7 HR. s-SCF was measured by ELISA as ng/ml. s-SCF basal levels
      were higher in LT that in HR (818 +/- 349 vs. 479 +/- 79, p = 0.005). A
      significant increase of s-SCF, peaking at postoperative day +3, was seen after LT
      (from 818 +/- 349 to 1212 +/- 461, p = 0.01) and HR (from 479 +/- 79 to 698 +/-
      122, p = 0.004). s-SCF peak levels were higher after LT than HR (p = 0.0008). At
      day +7 s-SCF concentration returned to baseline values. LT have a higher basal s
      SCF level than HR. These data show for the first time that liver injury affects s
      SCF level and suggest that SCF may be involved also in clinical liver
      regeneration.

PMID- 16801131
TI  - Reduced binding of FGF1 to mutant fibroblast growth factor receptor 3.
AB  - The activating mutation FGFR3-R248C in the D2-D3 linker region of fibroblast
      growth factor receptor 3 leads as germline mutation to the neonatal lethal
      syndrome thanatophoric dysplasia type I (TD1). As somatic mutation it has been
      found in cancer. We introduced into the murine FGFR3 the mutation R242C that is
      orthologoues to the human mutation R248C. A strong reduction in binding of the 16
      and 18 kDa forms of FGF1 to the mutant receptor was found, highlighting the
      importance of D2-D3 linker region of FGFR3 in determination of binding affinity
      to ligands. Another mutant, G374R, introduced into the murine FGFR3, is
      orthologoues to the human mutant FGFR3-G380R, and leads to achondroplasia (ACH).
      The binding of the 16 kDa and 18 kDa forms of FGF1 to this mutant receptor was
      the same as for wild-type FGFR3 in a cell-free system, but it was reduced in
      living cells. The data indicate a minor changes in conformation of FGFR3-G374R
      receptors at the cell surface that lead to reduced binding to FGF1.

PMID- 16801132
TI  - Control of ErbB signaling through metalloprotease mediated ectodomain shedding of
      EGF-like factors.
AB  - Epidermal growth factor (EGF)-like proteins comprise a group of structurally
      similar growth factors, which contain a conserved six-cysteine residue motif
      called the EGF-domain. EGF-like factors are synthesized as transmembrane
      precursors, which can undergo proteolytic cleavage at the cell surface to release
      a mature soluble ectodomain; a process often referred to as "ectodomain
      shedding". Ectodomain shedding of EGF-like factors has been linked to multiple
      zinc-binding metalloproteases of the matrix metalloprotease (MMP) and a
      disintegrin and metalloprotease (ADAM) families. Shedding can be activated by a
      variety of pharmacological and physiological stimuli and these activation events
      have been linked to the enhancement of metalloprotease activity, possibly via the
      action of intracellular signaling modules. Once shed from the cell surface, EGF
      like factors bind to a family of four cell surface receptors named ErbB-1, -2, -3
      and -4. Heterodimerization or homodimerization of these receptors following
      ligand binding drives intracellular signal transduction cascades, which eventuate
      in diverse cell fates including proliferation, differentiation, migration and
      inhibition of apoptosis. In addition to its role in driving normal developmental
      processes, a wealth of evidence now exists showing that de-regulated ErbB
      signaling is associated with the formation of tumors in a variety of tissues and
      that ectodomain shedding of EGF-like factors plays a critical event in this
      process. Thus, knowledge of the molecular mechanisms by which EGF-like factors
      are shed from the cell surface and the nature of the proteases and cellular
      signals that govern this process is crucial to understanding ErbB receptor
      signaling and potentially also in the development of novel cancer therapeutics
      targeting the ErbB pathway. This review focuses on the structure and function of
      EGF-like factors, and the mechanisms that govern the shedding of these
      transmembrane molecules from the cell surface.

PMID- 16801133
TI  - The duplicitous nature of the Lyn tyrosine kinase in growth factor signaling.
AB  - The Lyn tyrosine kinase is a unique member of the Src family of non-receptor
      protein tyrosine kinases whose principal role is to regulate signals through
      inhibitory receptors thereby promoting signal attenuation. Lyn is renowned for
      its role in B cell antigen receptor and FcepsilonRI signaling; however, it is
      becoming increasingly apparent that Lyn also functions in signal transduction
      from growth factor receptors including the receptors for GM-CSF, IL-3, IL-5, SCF,
      erythropoietin, CSF-1, G-CSF, thrombopoietin and Flt3 ligand. Numerous studies
      have implicated Lyn in growth factor receptor signal amplification, while a
      number also suggest that Lyn participates in negative regulation of growth factor
      signaling. Indeed Lyn-deficient mice are hyper-responsive to myeloid growth
      factors and develop a myeloproliferative disorder that predisposes the mice to
      macrophage tumours, with loss of negative regulation through SHP-1 and SHIP-1
      thought to be the major contributing factor to this phenotype. Developing a clear
      understanding of Lyn's role in establishing signaling thresholds in growth factor
      receptor signal amplification and signal inhibition may have important
      implications in the management of leukemias that may depend on Lyn activity.

PMID- 16801134
TI  - Syndecan-1 regulates FGF8b responses in S115 mammary carcinoma cells.
AB  - In murine mammary carcinoma cells Shionogi 115 (S115) testosterone induces
      phenotypical transformation which is largely due to expression of fibroblast
      growth factor (FGF) 8b. Concomitantly, the expression of the cell surface heparan
      sulfate proteoglycan syndecan-1 is down-regulated. However, if syndecan-1
      expression is maintained by transfection with a testosterone-driven syndecan-1
      construct, transformation does not occur. Here we have investigated how the down
      regulation of syndecan-1 expression in testosterone-treated S115 cells and the
      high level of expression in syndecan-1 transfected cells influence the cellular
      responses toward FGF8b. Our results show that high level of syndecan-1 is
      associated with a decreased magnitude and duration of the FGF8b induced Erk
      phosphorylation. This effect was observed regardless whether the cells were
      stimulated directly with exogenous FGF8b or with testosterone to induce autocrine
      FGF8b production. Moreover, syndecan-1 transfected cells did not respond to FGF8b
      stimulation by increase in the intracellular free calcium, whereas untransfected
      cells displayed a rapid (10 s) induction. These data suggest that, in S115 cells,
      syndecan-1 acts as a modulator of FGF8b signaling that can limit cellular
      responses to FGF receptor activation. The decreased levels of syndecan-1
      expression and upregulation of the FGF signaling system seen in many cancers may
      contribute to the proliferation of the malignant cells in vivo.

PMID- 16801135
TI  - Systemic corticosteroid therapy for acute asthma exacerbations.
AB  - Acute exacerbations of asthma may represent reactions to airway irritants or
      failures of chronic treatment. The costs to both the patient and society are
      high. Exacerbations often are frightening episodes that can cause significant
      morbidity and sometimes death. The emergency department (ED) visits and
      hospitalizations often required lead to significant health care expenses. Thus,
      preventing and optimizing management of acute exacerbations is critical.
      Corticosteroids are a cornerstone of asthma therapy. They have been shown to
      lower admission rates and reduce risk of relapse. This article provides an
      overview of the role of corticosteroids (including betamethasone, dexamethasone,
      methylprednisolone, and prednisolone) in the management of acute asthma
      exacerbations, with an aim toward effective decision making about the choice of
      therapy.

PMID- 16801136
TI  - A unique cause of asthma in a baker.
AB  - Occupational asthma has been a recognized cause of respiratory disease for
      centuries, and bakers' asthma, in particular, has been well described. This case
      report identifies egg white protein as the trigger of asthma in an atopic baker.
      It highlights the clinical spectra of bakers' asthma, emphasizing the importance
      of occupational exposures in adult onset asthma.

PMID- 16801137
TI  - A longitudinal analysis of the efficacy of environmental interventions on asthma
      related quality of life and symptoms among children in urban public housing.
AB  - In an environmental intervention study in public housing, we examined monthly
      Juniper Paediatric Asthma Quality of Life (QOL) Questionnaires for 51 children.
      Longitudinal analysis and spline models were used to identify time periods with
      significant improvements in QOL to inform judgments about causality. We found
      significant improvements in QOL, with moderate improvements before environmental
      interventions, increased rates of improvement immediately after, and reduced
      rates more than 5 months post-intervention. Effect modification analyses
      identified high-risk subpopulations and emphasized the importance of
      environmental, social, and economic conditions. Our results demonstrate the value
      of longitudinal techniques in evaluating the benefits of environmental
      interventions for asthma.

PMID- 16801139
TI  - Risk factors for respiratory symptoms and asthma in the residential environment
      of 5th grade schoolchildren in Taipei, Taiwan.
AB  - This study examined the association of residential environmental factors with
      respiratory symptoms and asthma in 2,290 fifth graders in Taipei, Taiwan. A self
      report survey questionnaire elicited experiences of respiratory symptoms, disease
      history, and characteristics of residential environmental factors from
      schoolchildren. The proportion of schoolchildren having physician-diagnosed
      asthma was 9.8% and suspected asthma was 16.1%. The proportions of having
      respiratory symptoms in the past 12 months ranged from 9.8% for wheezing without
      a cold to 40.5% for exercise-induced cough. Higher proportions of boys had non
      exercise-induced respiratory symptoms, physician-diagnosed asthma, and suspected
      asthma than girls (p < 0.05). Exposure to odoriferous chemical vapor was
      significantly associated with all seven respiratory symptoms considered in the
      study (p < 0.05). After adjusting for confounding factors including residential
      districts, gender, diagnosed allergy, and parental history of respiratory
      symptoms, odoriferous chemical vapors, gas leaks, dehumidifier use, presence of
      cockroaches at home, and leaky water/water puddle at home were significantly
      associated with the proportions of physician-diagnosed asthma or suspected asthma
      of the schoolchildren. The adjusted odds ratio (aOR) of physician-diagnosed
      asthma was 2.35 (95% confidential interval = 1.45-3.82) for odoriferous chemical
      vapor. The aOR of suspected asthma measure was 2.14 (95% CI = 1.40-3.26) for
      odoriferous chemical vapor. Odoriferous chemical vapor was the major risk factor
      of respiratory illness in the residential environment of schoolchildren in
      Taipei. Other household risk factors included gas leaks, dampness, and
      cockroaches at home.

PMID- 16801138
TI  - Co-administration of vaccination with DNA encoding T cell epitope on the Der p
      and BCG inhibited airway remodeling in a murine model of chronic asthma.
AB  - Therapeutic modalities of airway remodeling in asthma have proved to be
      unsuccessful regarding reversing the previously established chronic airway
      changes. Recently, the potential of plasmid DNA to inhibit the Th2 immune
      response has been demonstrated in animal models of asthma. Bacillus Calmette
      Guerin (BCG) immunization also induced immunomodulation, which appeared to be
      reliant on the properties of the interferon-gamma that was produced. Mice were
      immunized with house dust mite extract (HDM). At the 3 week point, we injected
      BCG subcutaneously into mice on three successive weeks. One week after the BCG
      injection, we immunized mice with the DNA plasmid encoding for murine T-cell
      epitope on Dermatophagoide pteronyssinus 2 thrice weekly. At 9 weeks after
      immunization, we measured airway responsiveness. Twenty four hours later, we
      performed bronchoalveolar lavage and histological examinations. Co-administration
      of DNA vaccination and BCG resulted in a partial suppression of the
      overproduction of goblet cells and the thickness of the peribronchial smooth
      muscle in ongoing allergic responses. In the bronchoalveolar lavage fluid, the
      number of total cells and eosinophils was reduced, and regarding the change of
      cytokines, the concentration of IL-4 was also decreased, but interferon-gamma was
      increased in the co-administration group, opposed to the asthma group. These
      results suggest that co-administration of vaccination with the DNA encoding T
      cell epitope and BCG are effective regarding ongoing allergic response and might
      constitute an ideal method for combating allergic disease in the future.

PMID- 16801140
TI  - Gender differences in asthma experience and disease care in a managed care
      organization.
AB  - The purpose of this study was to describe gender differences in asthma in a
      managed care organization. We collected data from a patient survey, electronic
      administrative data, and hard-copy chart reviews. Women reported significantly
      lower general health status, more symptoms and greater severity of asthma, more
      activity limitations, more use of asthma-relieving medications, and more acute
      visits for asthma than men. Conversely, women tended to report better asthma care
      measures. These gender disparities warrant further study to support appropriate
      adjustment of clinical care and health-care-related services for women.

PMID- 16801141
TI  - Reducing home triggers for asthma: the Latino community health worker approach.
AB  - This study assessed the ability of a community health worker asthma intervention
      to change home asthma triggers. A total of 56 children and 47 adults with asthma
      were enrolled. Home trigger scores for the children averaged 2.8 at the initial
      home visit and then 2.3, 2.1, and 2.0 at 3, 6, and 12 months. Home trigger scores
      for the adults showed a similar trend. Every home visit was associated with a
      0.32 reduction in home trigger score (p < 0.01) for children and a 0.41 reduction
      (p < 0.01) for adults. This intervention shows promise as a way to reduce asthma
      triggers in urban low-income Latino communities.

PMID- 16801142
TI  - Readability characteristics of consumer medication information for asthma
      inhalation devices.
AB  - PURPOSE: Successful control of asthma relies heavily on patient adherence to
      prescribed inhalation therapies. Many patients are unable to use inhalers
      correctly and, therefore, do not reap the full therapeutic benefits. The purpose
      of this study was to assess the readability and related characteristics of
      Consumer Medication Information (CMI) for all prescription asthma inhalation
      devices currently available in the United States. METHODS: We identified all
      brand-name (n = 18) and generic (n = 2) asthma inhalation devices currently
      available in the United States. English language CMI was obtained from
      pharmaceutical manufacturers of each identified product. The CMI from these
      products was evaluated for readability characteristics, including reading grade
      level using the Fry formula, text point size, dimensions (length and width),
      diagrams, and directions. RESULTS: The mean Fry readability of the CMI was at
      grade level 8.2 +/- 1.5 (range = 5-11), while the average text point size was 9.2
      +/- 2.2 (range = 6-12). The mean length of the pages on which the CMI was printed
      was 33.7 +/- 21.5 cm, while the average width of pages was 12.9 +/- 9.5 cm. There
      was an average of 6.2 +/- 3.6 (range = 2-12) illustrations per CMI, while a
      device overview diagram was included in 14 (70%). Eleven (n = 11) instructions
      included detailed step-by-step diagrams to supplement directions. CONCLUSIONS:
      Overall, most CMI for prescription inhalers is presented with a reading
      difficulty level, text size, diagrams, and instructions that make it suboptimal
      for patient education. Prescription inhaler manufacturers should consider
      revising their CMI to comply with generally accepted guidelines preparing patient
      education information.

PMID- 16801143
TI  - Differences in the evaluation and management of exercise-induced bronchospasm
      between family physicians and pulmonologists.
AB  - Previous studies have demonstrated that specialists and generalists differ in the
      evaluation and management of asthma especially in terms of use of objective
      testing. We speculated that there also may be differences in the diagnosis and
      management of exercise-induced respiratory complaints. An Internet survey was
      sent to samples of pulmonologists and family physicians. Our data suggests that
      pulmonologists are much more likely to order bronchoprovocation testing than
      family physicians, and family physicians are more likely to start any empiric
      therapy than perform bronchoprovocation testing when exercise-induced
      bronchospasm is suspected. These differences may lead to inaccurate or missed
      diagnoses and unnecessary morbidity.

PMID- 16801144
TI  - Treatment regimens and health care utilization in children with persistent asthma
      symptoms.
AB  - This study evaluated the anti-inflammatory medication regimens in children with
      persistent asthma, determined their health care utilization patterns, and
      evaluated factors associated with failure to seek and/or receive appropriate
      treatment. Parents of 68% of children who qualified for anti-inflammatory
      medications by National Asthma Education and Prevention Program (NAEPP)
      guidelines reported their use. However, only 14% received an optimal regimen
      (mild intermittent symptoms), while 55% were still symptomatic despite reported
      medications (suboptimal regimen). Nearly half of symptomatic children did not
      have a health care visit; of those who did, 61% had no corrective action
      documented. Factors contributing to variations in regimen and utilization are
      discussed.

PMID- 16801145
TI  - Childhood asthma under the north face of Mount Everest.
AB  - We assessed prevalences of symptoms of asthma, allergic rhinitis, and atopic
      eczema and their associations with environmental exposures among school children
      living in high altitude and rural Tibet. After watching an asthma symptom video,
      2.8% of the children reported ever wheezing at rest and 1.4% ever severe
      wheezing. Residential dampness problems were the only environmental exposure that
      was clearly associated with children's symptoms (odds ratios 1.3 to 2.5), even if
      several other exposures were common. The low symptom prevalences are in
      accordance with the hypothesis that the western lifestyle in some way increases
      the risk of asthma.

PMID- 16801146
TI  - Pediatric asthmatic patients have low serum levels of monocyte chemoattractant
      protein-1.
AB  - Serum levels of MCP-1 were measured in children with and without asthma in order
      to determine a possible correlation between the MCP-1-2518A/G polymorphism, serum
      levels of MCP-1 and asthma. Two groups of subjects -160 children with asthma and
      158 healthy children were screened with a PCR-based genotyping assay. Serum MCP-1
      level was measured by ELISA. The -2518G allele occurred at a significantly higher
      frequency in asthmatic children than in controls. The mean serum MCP-1 level was
      significantly lower in the asthmatic than in the control children. There was no
      significant association between the MCP-1 genotypes and the serum MCP-1 levels.

PMID- 16801148
TI  - Prism adaptation changes perceptual awareness for chimeric visual objects but not
      for chimeric faces in spatial neglect after right-hemisphere stroke.
AB  - Prism adaptation can ameliorate some symptoms of left spatial neglect after right
      hemisphere stroke. The mechanisms behind this remain unclear. Prism therapy may
      increase exploration towards the contralesional side, yet without improving
      perceptual awareness, as apparently for the left side of chimeric face stimuli
      (Ferber et al. 2003). However, other prism studies suggest that perceptual
      awareness might be improved (e.g., Maravita et al., 2003). We tested the impact
      of prism therapy on visual awareness for the left side of chimeric objects as
      well as chimeric faces, in three neglect patients. Prism therapy dramatically
      improved awareness for the identity of the left side of chimeric non-face
      objects, but had no effect on judging expressions for chimeric faces. The latter
      may thus be unique in showing no prism benefit.

PMID- 16801149
TI  - The understanding of quantifiers in semantic dementia: a single-case study.
AB  - This study investigates the processing of quantifiers in a patient (AM) with
      semantic dementia. Quantifiers are verbal expressions such as "many" or "a few",
      which refer semantically to quantity concepts although lexically they are like
      non-quantity words. Patient AM presented with preserved understanding of
      quantifier words and impaired understanding of non-quantifier words of the same
      frequency. In parallel to this, he showed preserved numerical knowledge and
      impaired comprehension of the meaning of words, objects, and of linguistic
      concepts. These results suggest that the neural organization of quantifiers is
      within the numerical domain as they pattern with numerical concepts rather than
      linguistic concepts. These data reinforce the evidence that numerical knowledge
      is functionally distinct from non-numerical knowledge in the semantic system and
      indicate that the semantic referent rather than the stimulus format is more
      relevant for semantic processing.

PMID- 16801150
TI  - Measuring the hemodynamic response in chronic hypoperfusion.
AB  - Although structural brain scans help assess brain injury in stroke, they cannot
      identify regions that are functionally disabled due to disrupted perfusion.
      Perfusion and functional MRI have the potential for determining the functional
      consequences of stroke. Here we examine the effectiveness of functional MRI to
      measure brain function in a single patient (LB) with chronic hypoperfusion. When
      LB made sustained hand movements we observed a sustained decrease in the fMRI
      signal, while normal individuals exhibit a sustained increase in signal while
      conducting this task. This work has clear implications for understanding stroke
      using functional MRI.

PMID- 16801151
TI  - The different frameworks underlying abstract and concrete knowledge: evidence
      from a bilingual patient with a semantic refractory access dysphasia.
AB  - We report the case of a bilingual patient (IRQ) who acquired a semantic
      refractory access dysphasia following a middle cerebral artery stroke. In a
      series of spoken word-written word matching tasks, the degree of semantic
      similarity between target and distractor items was found to affect the accuracy
      of IRQ's identification of concrete but not abstract words. By contrast, the
      degree of semantic association between target and distractor items was found to
      affect response accuracy when identifying abstract but not concrete words. These
      results provide further corroboration for the notion that abstract concepts are
      supported by an associative representational network whereas concrete concepts
      are supported by a categorical representational framework. We also demonstrate an
      equivalent refractory deficit of comprehension in both English and Arabic. In
      addition, we provide the first documented evidence of a category-specific
      refractory deficit of knowledge for abstract words.

PMID- 16801152
TI  - Divergent patterns of aggressive and neurocognitive characteristics in acquired
      versus developmental psychopathy.
AB  - An analogy is often drawn between patients with personality changes following
      orbitofrontal cortex lesions and individuals with developmental psychopathy. We
      present patient CL, who had acquired psychopathy following an orbitofrontal
      cortex lesion. Unlike previous studies, CL was assessed on a valid and reliable
      measure of psychopathy and was compared with controls and patients with
      developmental psychopathy on measures of instrumental (re)learning, extinction,
      emotional processing, and social cognition. The results provide further support
      for the notion that acquired and developmental forms of psychopathy are
      associated with dissociable neurocognitive deficits that leave each at different
      levels of risk for reactive and instrumental aggression.

PMID- 16801153
TI  - Suggestive evidence for an involvement of the right hemisphere in the recovery
      from childhood aphasia: a 3-year follow-up case study.
AB  - We describe the case of an 11-year-old, previously healthy, pre-puberal, right
      handed girl with acquired aphasia following an extensive cerebral hemorrhage into
      a left hemisphere brain tumor. A 3-year follow-up evaluation of the girl's
      communicative performance showed an incomplete recovery of linguistic abilities
      with a good recovery of comprehensive components, but persisting severe
      impairment in expressive language. At the end of the follow-up period, with the
      aim of assessing the lateralization of some linguistic abilities, we carried out
      an experimental investigation using tachistoscopic reading and object naming
      tests along with a dichotic listening test. All these tests showed a clear left
      field/left ear-right hemisphere advantage. We discuss both clinical and
      experimental results with regard to implications for the linguistic abilities of
      the right hemisphere in late versus early childhood and its interaction with
      aetiology in the recovery from acquired childhood aphasia.

PMID- 16801154
TI  - Long-term habituation of the smile response with deep brain stimulation.
AB  - Human and animal research has shown that the ventral striatum, including the
      nucleus accumbens, may play a critical role in mediating positive emotions.
      Recently we described a subject with obsessive-compulsive disorder who intra
      operatively exhibited the acute onset of an asymmetric smile and acute positive
      emotional change with contralateral deep brain stimulation (DBS) in either the
      right or left nucleus accumbens and anterior limb of the internal capsule region.
      The purpose of the present study was to examine the stability of the stimulation
      induced smile(s) over a 12-month period. Custom computer software objectively
      quantified left and right facial movement during DBS. Although stimulation
      induced smiles were elicited at one and two months post-surgery, they were no
      longer present from 3-12 months following chronic high frequency DBS. The smiles
      could not be elicited even with long washout periods. These findings imply
      potential long-term habituation and changes in the neural chemistry (possibly
      neuroplasticity) induced by chronic DBS.

PMID- 16801155
TI  - Left ipsilesional neglect for visual imagery: a mental image generation
      impairment?
AB  - In this article, we describe a patient, CN, with unilateral left posterior brain
      damage, who shows a rare occurrence of left ipsilesional neglect limited to
      mental representations. CN's clinical pattern is consistent with the hypothesis
      that different mechanisms underlie perceptual and representational neglect. We
      also discuss an interpretation of representational neglect based on the different
      involvement of the two hemispheres in visual imagery processes. In particular,
      left brain lesions do not present the typical strong contralesional bias and may
      lead to an impairment of mental generation of either side of the image, depending
      on pre-morbid and methodological factors.

PMID- 16801157
TI  - Growth hormone therapy-established uses in short children.
AB  - Since the first reported efficacious use of human growth hormone in 1958,
      numerous children have been treated with this hormone. This review discusses the
      five indications for use of human growth hormone in children that have been
      approved to date by the United States Food and Drug Administration. CONCLUSION:
      Further, long-term studies will be needed to address the optimal use of this
      hormone in each of these conditions.

PMID- 16801158
TI  - Non-conventional use of growth hormone therapy.
AB  - Human growth hormone therapy is allowed in certain clinical conditions according
      to national healthcare criteria. Growth hormone, however, produces a wide
      spectrum of effects. Linear growth is only one of the many expected results, and
      there are interesting possibilities to explore which could provide additional
      means of improving the quality of life for the ever-increasing numbers of chronic
      paediatric patients. CONCLUSION: In this review, we discuss the rationale for and
      possibility of using growth hormone therapy in some conditions not strictly
      related to growth hormone deficiency.

PMID- 16801159
TI  - Dilated cardiomyopathy in children.
AB  - Dilated cardiomyopathy (DCM) is a rare disease in the paediatric population. We
      analysed the epidemiology, clinical features and role of immunotherapy in the
      treatment of myocarditis. On the basis of experimental evidence, indicating that
      autoimmunity might play a role in the development of myocarditis, we treated
      children affected by myocarditis with immunosuppressive therapy, and we present
      here our series. The future availability of reliable prognostic markers should
      allow treatment of only those children with myocarditis who do not spontaneously
      recover. The possibility that DCM with myocarditis is a distinct pathological
      entity from the non-inflammatory form of DCM is suggested. CONCLUSION: The high
      long-term survival rate observed in our children with myocarditis is probably due
      to the effect of short-term immunosuppression. This result is at odds with
      previously published series of conventionally treated children, whose survival
      probability at 1 y was approximately 0.60.

PMID- 16801160
TI  - What makes the heart fail? New insights from defective genes.
AB  - Dilated cardiomyopathy (DCM) is an idiopathic, genetically heterogeneous disorder
      characterized by heart failure and arrhythmia. Over the past decade, the
      molecular basis for DCM has been partially uncovered by discovery of mutation in
      genes encoding cystoskeletal, sarcomeric, nuclear membrane, and sarcoplasmic
      reticulum proteins. These findings have implicated pathogenic mechanisms whereby
      structural integrity, contractile force dynamics, and calcium regulation within
      the cardiac myocyte are perturbed. Recognition of dilated and hypertrophic
      cardiomyopathies as allelic disorders has provided the opportunity to identify
      genotype-phenotype relationships and to gain new insight into pathways leading to
      cardiac failure and hypertrophy. CONCLUSION: Collectively, family-based studies
      of DCM provide the rationale for clinical screening in first-degree relatives,
      regardless of family history or age of the index case.

PMID- 16801161
TI  - Unifocalization and repair of pulmonary atresia with ventricular septal defect
      and major aortopulmonary collateral arteries.
AB  - AIM: To correlate anatomic and genetic features of paediatric patients with
      pulmonary atresia, ventricular septal defect (VSD) and multiple aortopulmonary
      collateral arteries with surgical outcome. METHODS: 44 consecutive patients aged
      33 +/- 40 mo underwent either primary one-stage unifocalization (n = 32) or
      palliative right ventricular outflow tract reconstruction (n = 12) followed by
      secondary unifocalization and repair (n = 10) based on preoperative morphometric
      and functional evaluation of pulmonary blood sources. Chromosome 22q11.2
      microdeletion occurred in 41% of cases. Combined VSD closure during one-stage
      procedures was guided by an intraoperative pulmonary flow study. Complete repair
      was accomplished in 35 cases (83%, 95% CI 72-95%). Variables examined included
      occurrence of confluent intrapericardial pulmonary arteries, central pulmonary
      arteries, confluent intraparenchymal pulmonary arteries, dominant collateral or
      pulmonary arteries, and chromosome 22q11.2 microdeletion. The sensitivity and
      specificity of the pulmonary flow study in predicting postoperative pulmonary
      haemodynamics were also tested. RESULTS: Eight-year actuarial survival and
      freedom from reoperation were 85% and 63%, respectively. Sensitivity and
      specificity of the pulmonary flow study were 94% and 100%, respectively. None of
      the anatomical variables examined was significantly related to the outcome of
      treatment. The only statistically relevant association was detected between
      survival and occurrence of 22q11.2 microdeletion (p < 0.003). Logistic analysis
      showed an increased likelihood of positive outcome in relation to first- (p <
      0.02) or second-stage (p < 0.04) complete correction. CONCLUSION: Morphology of
      pulmonary blood supply has no major impact on surgical outcome. Pulmonary flow
      study is a highly specific and sensitive intraoperative test. Chromosome 22q11.2
      microdeletion remains the only variable significantly affecting survival.

PMID- 16801162
TI  - Stones, bones, and heredity.
AB  - Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and
      osteodystrophy. Most are rare, such that the full spectrum of clinical expression
      is difficult to appreciate. Diagnosis is further complicated by overlap of
      clinical features. Dent's disease and primary hyperoxaluria, inherited causes of
      calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis
      in early childhood and renal failure that can occur at any age but is seen more
      often in adulthood. Bone disease is an inconsistent feature of each. Dent's
      disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific
      CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of
      Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule
      dysfunction, including phosphate wasting, are primarily responsible for the
      clinical manifestations. Low-molecular-weight proteinuria is characteristic.
      Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria,
      type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine
      glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic
      cells results in the hyperoxaluria responsible for clinical features. Definitive
      diagnosis is by liver biopsy with measurement of enzyme activity, with DNA
      mutation analysis used increasingly as mutations and their frequency are defined.
      These disorders of calcium urolithiasis illustrate the value of molecular
      medicine for diagnosis and the promise it provides for innovative and more
      effective future treatments.

PMID- 16801163
TI  - Cystinuria.
AB  - Cystinuria is an autosomal recessive disorder characterized by impaired transport
      of cystine, lysine, ornithine and arginine in the proximal renal tubule and in
      the epithelial cells of the gastrointestinal tract. Following recent progress in
      the genetic understanding of the disease, the traditional classification, based
      on the excretion of cystine and dibasic amino acids in obligate heterozygotes,
      may no longer be considered valid. A new classification is therefore needed: type
      A due to two mutations of SLC3A1 on chromosome 2, and type B due to two mutations
      of SLC7A9 on chromosome 19. The possibility of a third type, AB, with one
      mutation on each of the above-mentioned genes, is left open, but is unlikely.
      Clinical data show that cystinuria is more severe in males than in females in
      terms of stone production and early age of onset. The two types of cystinuria (A
      and B) have a similar outcome. A mild renal failure is present in 17% of
      patients. Medical treatment of this disorder is possible, but requires a
      composite approach: urine dilution and alkalization, and the use of drugs to form
      chemical bonds with the sulphydryl domains of the cystine molecule, which lower
      the amount of free cystine in the urine. CONCLUSION: Following new achievements
      in the genetics of cystinuria, a new classification has been proposed. Cystinuria
      is more severe in males than in females, but only rarely leads to renal
      insufficiency. The two types of cystinuria have a similar clinical outcome. A
      combined medical treatment may be effective in reducing renal stone incidence.

PMID- 16801164
TI  - Surgery in disabled children: general gastroenterological aspects.
AB  - Cerebral palsy (CP) is a non-progressive but not unchanging disorder of movement
      and/or posture, due to an insult to or anomaly of the developing brain.
      Gastrointestinal surgery can play a role in the treatment of pathologies
      frequently associated with a condition of neurological impairment such as gastro
      oesophageal reflux disease (antireflux procedure), feeding difficulties
      (percutaneous endoscopic gastrostomy/jejunostomy) and swallowing difficulties
      (ligation of salivary gland ducts). Gastro-oesophageal reflux occurs in up to 70
      75% of children with cerebral palsy. Children with gastro-oesophageal reflux
      disease (GERD) may present with feeding difficulties, recurrent vomiting and
      recurrent chest infection associated with poor growth and nutrition, reactive
      airway disease particularly nocturnal asthma, choking attacks, anaemia, and
      wheezing. Nutritional deprivation in children with cerebral palsy is the
      summation of several factors which result in reduced intake. Percutaneous
      endoscopic gastrostomy (PEG) has radically changed the handling of children with
      nutritional problems who, before the introduction of this procedure, were force
      fed parenterally or enterally, by nasogastric tube, conventional surgical
      gastrostomy or central venous access. In children with CP, PEG is the preferred
      technique for long-term enteral feeding. Swallowing dysfunction is the main cause
      of drooling in cerebral palsy, and medical treatment is often inefficient.
      Surgical treatment involves neurectomy, translocation of the salivary duct,
      salivary gland resection or salivary duct (parotid and submandibular) ligation.
      CONCLUSION: This review focuses on the role of surgery in managing
      gastrointestinal aspects in children with CP and, in particular, surgical
      experience at our department with fundoplication, PEG placement and ligation of
      salivary ducts.

PMID- 16801165
TI  - Macrophage activation syndrome in juvenile idiopathic arthritis.
AB  - Macrophage activation syndrome (MAS) is a rare and potentially lethal
      complication of chronic rheumatic diseases of childhood, in particular of
      systemic-onset juvenile idiopathic arthritis (s-JIA), resulting from uncontrolled
      activation and proliferation of T lymphocytes and macrophages. The onset, acute
      and dramatic, may mimic a flare of the underlying disease or a severe sepsis.
      Diagnosis is difficult and, until now, no specific criteria have been developed.
      Laboratory data show pancytopenia, coagulopathy, low ESR and low concentrations
      of serum albumin, and high levels of ferritin, liver enzymes and triglycerides.
      Activated macrophages are found in various organs, particularly in bone marrow.
      Most hypotheses on the mechanism underlying MAS are based on the data obtained in
      primary haemophagocytic lymphohistiocytosis (HLH), a genetic disease very similar
      to MAS. Prompt diagnosis is essential because prognosis is highly related to
      early treatment. The first approach was to use intravenous methylprednisolone
      pulse therapy; cyclosporin A was proposed in patients resistant to steroids. We
      describe nine patients affected by haemophagocytosis: seven patients developed
      MAS and two patients developed HLH. A child with s-JIA developed three episodes
      of MAS. After the third episode, as there was no improvement with pulses of
      methylprednisolone and cyclosporine, he was successfully given etanercept.
      CONCLUSION: Our data, together with a similar, published observation, suggest
      that the TNF inhibitor etanercept is potentially useful for obtaining remission
      in children not responding to steroids and cyclosporin A.

PMID- 16801166
TI  - Ethical issues in neonatal intensive care and physicians' practices: a European
      perspective.
AB  - An international project (EURONIC) was carried out to explore the end-of-life
      decision-making process in a large, representative sample of neonatal intensive
      care units (NICUs) in eight western European countries: France, Germany, Great
      Britain, Italy, Luxembourg, the Netherlands, Spain and Sweden. Structured
      questionnaires were used to record data on NICU organization and policies, and to
      survey staff views and practices regarding ethical decision-making. One hundred
      and twenty-two NICUs were recruited by census or random sampling (response rate
      86%); 1235 physicians and 3115 nurses completed the staff questionnaire (response
      rates 89 and 85%, respectively). This paper focuses on the physicians' answers.
      In all countries but Italy, most physicians reported having been involved at
      least once in setting limits to intensive care because of a baby's incurable
      condition and/or poor neurological prognosis. Adopted strategies varied between
      countries. Practices such as the continuation of current treatment without
      intensifying it and the withholding of emergency manoeuvres appeared widespread.
      In contrast, the frequency of doctors reporting withdrawal of mechanical
      ventilation was highest in the Netherlands (93%), Sweden (91%) and the Great
      Britain (88%), intermediate in France and Germany, and lowest in Spain and Italy
      (34 and 21%, respectively). CONCLUSION: Ethically problematic clinical cases are
      approached differently in the various countries. The findings of this study may
      provide an opportunity for physicians to review their practices critically, in
      light of how other colleagues proceed, and foster an open discussion about these
      difficult issues.

PMID- 16801167
TI  - Infant leukaemia: clinical, biological and therapeutic advances.
AB  - Infant acute lymphoid leukaemia (IALL) represents a distinct subset with an
      extremely poor response to therapy, despite major progress in the treatment of
      childhood leukaemia. However, several studies have shown that, even in this
      generally considered homogeneous group, a distinction could be made with regard
      to prognosis. The outcome of IALL patients with ALL-1/MLL rearrangements at the
      11q23 cytogenetic band, early pre-B immunophenotype, high WBC count and age below
      6 mo is significantly worse than in patients without these characteristics, and
      current therapies appear inadequate in a significant number of cases. Therefore,
      an international protocol (Interfant 99) was recently started, using a more
      aggressive approach, which included lymphoid- and myeloid-specific drugs, and
      indications for stem-cell transplantation. We reviewed the clinical
      characteristics of the disease, the results of several recent international
      clinical trials, and our experience with 16 infants with acute lymphoid leukaemia
      diagnosed and treated at our institution. CONCLUSION: It is extremely important
      to stratify patients for prognosis, taking into account clinical and biological
      variables with independent prognostic value. The aim is to select more adequate,
      risk-adapted, therapeutic strategies which also consider related or unrelated
      bone marrow transplant consolidation for patients with very poor prognosis.

PMID- 16801168
TI  - The Nobel Prize for 1904 to Ivan Petrovich Pavlov (1849-1936): Function of the
      gastrointestinal tract.

PMID- 16801169
TI  - Time to screen for proteinuria?
AB  - Screening for proteinuria in childhood is performed in some countries but remains
      a controversial subject. During the last decade, a greater understanding of the
      importance of proteinuria for the long-term prognosis of children with renal
      diseases has been gained. Exciting new data also show that proteinuria is a
      prognostic factor for long-term cardiovascular outcome. CONCLUSION: In my
      opinion, there are still not strong enough reasons to support the routine
      screening of healthy children for proteinuria.

PMID- 16801170
TI  - General vaccination of children against influenza?
AB  - Due to the high incidence of influenza in children, general vaccination has been
      discussed. There are, however, reasons to believe that general vaccination of
      children will not solve the influenza problem because influenza vaccines induce
      type-specific immunity of short duration. CONCLUSION: Vaccination of several
      cohorts of children will be a tremendous commitment, probably with little hope of
      success in decreasing the morbidity and spread of influenza.

PMID- 16801171
TI  - Influenza in children.
AB  - Excess mortality associated with annual influenza epidemics is highest among
      persons over 65 y of age, and therefore influenza is often regarded as an illness
      of the elderly population. Ample evidence indicates, however, that the burden of
      influenza is also substantial in children, and that children have a central role
      in the spread of influenza in the community during epidemics. Vaccination of
      children against influenza could bring about substantial health benefits not only
      to children themselves but also to persons in other age groups. CONCLUSION:
      General awareness about the total impact of influenza in children should be
      increased among both healthcare personnel and the parents of children. More
      widespread vaccination of children should be considered to decrease the burden of
      influenza on children and wider society.

PMID- 16801172
TI  - Urological complications and copper replacement therapy in childhood Menkes
      syndrome.
AB  - BACKGROUND: Urological complications are frequent in Menkes syndrome, a very rare
      X-linked recessive disorder of copper (Cu) metabolism. AIM: To evaluate the role
      of Cu therapy in preventing the progression of urological complications. SUBJECTS
      AND METHODS: We retrospectively enrolled 57 patients with Menkes syndrome (55
      published case reports and two of our own unpublished cases) and investigated the
      reported urological complications, distinguishing the patients with or without Cu
      replacement therapy and evaluating the efficacy of this therapy in the prevention
      of urological complications. RESULTS: The most frequent urological complication
      was bladder diverticulum (38.6% of the total patients); obstruction bladder
      outflow and rupture of the kidney were less frequent (both 1.8% of the total).
      The number of congenital urological complications increased progressively by age
      category; in fact, 77.8% of patients did not report urological complications at
      the age of 0.4+/-0.2 y, and 28.6% of them displayed > or = two congenital
      urological complications at the age of 9.3+/-2.6 y. The percentage of urological
      complications found in younger patients not on Cu therapy did not differ from
      that of older patients treated with Cu therapy. A comparison between patients of
      the same age interval, who were or were not treated with Cu, showed that treated
      children had fewer urological complications than untreated children. CONCLUSION:
      Our investigation suggests that Cu therapy in patients with Menkes syndrome does
      not prevent the progression of urological complications; however, it might delay
      their worsening.

PMID- 16801173
TI  - Pleural effusions in the neonate.
AB  - INTRODUCTION: Pleural effusions are rare in the neonate and may be associated to
      several clinical conditions. Only a few series of pleural effusions in the fetus
      and newborn are described in the literature. AIM: This study was undertaken to
      determine more accurately the causes and prognostic significance of pleural
      effusions in a population of high-risk neonates. MATERIALS AND METHODS: A
      retrospective chart review of 62 neonates admitted to the neonatal intensive care
      unit of six medical centers in the north of Portugal, between 1997 and 2004, that
      presented the diagnosis of pleural effusion. RESULTS: 33M/29F newborns; preterms
      47 (76%); GA 33 (25-40) wk; BW 1830 (660-4270) g; C-section 39 (63%). Pleural
      effusions were congenital in 20 (32%) newborns and acquired in 42 (68%).
      Congenital pleural effusions occurred as fetal hydrops in 11 (18%) patients and
      as chylothorax in 9 (15%). In four cases of hydrops, the cause was a congenital
      chylothorax. Congenital chylothorax (n=13) was the most common (65%) congenital
      pleural effusion in this study. The incidence of congenital chylothorax was
      1:8.600 deliveries and male:female ratio was 2:1. Mortality occurred in five
      newborns due to pulmonary hypoplasia. Traumatic (iatrogenic) were the most
      frequent (n=31) acquired pleural effusions. These included 8 (13%) cases of
      hemothorax and 8 (13%) cases of total parenteral nutrition leakage. Pleural
      effusions after intra-thoracic surgery were mainly (79%) chylothoraces. There
      were 11 (26%) non-iatrogenic acquired pleural effusions. No mortality was
      associated with acquired pleural effusions. CONCLUSIONS: Congenital pleural
      effusions usually occur as hydrops or congenital chylothorax. Traumatic
      (iatrogenic) are the most frequent acquired pleural effusions in a tertiary NICU.
      Pleural effusions after intra-thoracic surgery are mainly chylothoraces. Non
      iatrogenic acquired pleural effusions are associated to several clinical
      conditions, and mortality is usually associated to the underlying condition.

PMID- 16801174
TI  - Inflicted traumatic brain injury (ITBI) or shaken baby syndrome (SBS) in Estonia.
AB  - BACKGROUND: Inflicted traumatic brain injury (ITBI) or shaken baby syndrome (SBS)
      is recognized as a major cause of disability and death in the paediatric
      population. AIM: To find out the incidence of ITBI in Estonia. METHODS: 26 cases
      of ITBI were recognized: four children died, 22 survived. RESULTS: Of 26
      children, 20 (77%) were boys and six (23%) were girls. Median age at admission to
      hospital was 3.9 mo, and the boys were younger than the girls. CONCLUSION: The
      overall incidence of ITBI was 28.7 per 100,000 infants. In the prospective group
      the incidence was 40.5 per 100,000, and in retrospective group 13.5 per 100,000.
      ITBI is not rare but not always a recognized form of child abuse. Healthcare
      professionals should be more aware of this condition.

PMID- 16801175
TI  - Decreasing ratio of plasma N-terminal pro-B-type natriuretic peptide and B-type
      natriuretic peptide according to age.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and the N-terminal fragment of
      proBNP (NT-proBNP) seem to be useful diagnostic tools also in children with
      cardiac disease. Recent data suggest that plasma levels of both peptides show
      different patterns from infancy to adolescence. AIM: To investigate the
      relationship of BNP and NT-proBNP in children and adolescents according to age.
      SUBJECTS AND METHODS: In 46 individuals without cardiac disease (22 males, 24
      females, aged 0.4-17.5 years) and 30 patients with congenital heart disease (17
      males, 13 females, aged 0.2-18.4 years), plasma levels of BNP and NT-proBNP were
      measured in the same sample (triage BNP assay, Biosite and Elecsys NT-proBNP
      assay, Roche Diagnostics). RESULTS: The range of BNP plasma levels was 5-32 pg/ml
      in individuals without heart disease and 5-1300 pg/ml in the patient group, the
      range of NT-proBNP was 10-298 pg/ml and 30-18,966 pg/ml, respectively. In both
      groups, the ratio NT-proBNP/BNP decreased with increasing age (P<0.001).
      CONCLUSION: Although proBNP is cleaved into the two fragments NT-proBNP and BNP,
      there is a decreasing ratio of NT-proBNP/BNP with increasing age caused probably
      by age-dependent differences in the metabolic clearance of both peptides. This
      has to be considered in comparison studies on BNP and NT-proBNP regarding their
      benefit to paediatric cardiology.

PMID- 16801176
TI  - ApoB-100 and ApoB/ApoA-1 ratio in children and adolescents from families with
      very early myocardial infarction.
AB  - AIM: The relationship between apolipoprotein B, LDL/ApoB, ApoB/ApoA-1, lipids and
      a family history of very early myocardial infarction (parent and/or grandparent
      <45 years) was studied in 46 children compared with 64 controls. METHODS: 19
      children came out of families with a myocardial infarction (MI) of the father and
      27 children with MI of a grandparent. RESULTS: In the whole risk group LDL-C,
      ApoB and ApoB/ApoA-1 ratio showed the most significant relationship, whereas in
      children from families with MI of the father ApoB level showed the strongest
      association with family history of MI. No relationship could be found for ApoA1,
      HDL-C and LDL/ApoB. CONCLUSION: Our results show that levels of ApoB, LDL-C and
      ApoB/ApoA-1 might be better predictors in children from families of very early MI
      as compared with ApoA-1, HDL-C and LDL/ApoB.

PMID- 16801177
TI  - pH and nitric oxide synthase activity and expression in bovine aortic endothelial
      cells.
AB  - AIM: Nitric oxide (NO) plays an important role in the transition from
      intrauterine to extrauterine life. If this transition fails, a condition called
      persistent pulmonary hypertension of the neonate (PPHN) may develop. The current
      treatment modalities for this disease include induction of alkalosis by
      hyperventilation or alkali infusion, inhaled nitric oxide (iNO) and
      extracorporeal membrane oxygenation. There is evidence from animal studies that
      the elevated pH, not the low pCO2 is responsible for the resultant pulmonary
      vasodilatation. In this study, we examined the effect of pH on the activity and
      expression of endothelial nitric oxide synthase (eNOS) in cultured bovine aortic
      endothelial cells (BAEC) as a possible explanation for the pH dependent drop in
      pulmonary vascular resistance. METHODS: BAEC were exposed to a pH gradient of 7.1
      7.6 for 4 h (short-term) and 16 h (long-term). Standard Western blotting
      technique was used to detect expression of eNOS. Activity was measured by an
      indirect assay using bovine aortic smooth muscle cells (BASM) as reporter cells
      and measuring cGMP levels as a marker of NO production. The cells were exposed to
      the pH gradient for a total of 4 h and measurement were made at 30, 60 and 90
      min, and 2, 3 and 4 hours. RESULTS: eNOS activity and expression remained
      unchanged during the four and sixteen hours of exposure. CONCLUSION: In this in
      vitro experiment, we could not demonstrate an alkalosis-induced increase in eNOS
      activity and expression. The clinically observed pH dependent vasodilatation does
      not appear to be directly mediated through the induction of eNOS.

PMID- 16801178
TI  - The timing of complementary feeding of infants in Switzerland: compliance with
      the Swiss and the WHO guidelines.
AB  - BACKGROUND: The importance of adequate complementary feeding of infants is
      increasingly acknowledged. Little is known of the actual complementary feeding
      practices in Switzerland. AIM: To report the prevalence of adequate timing of
      complementary feeding, comparing the compliance to Swiss and World Health
      Organization (WHO) guidelines, and to investigate factors influencing infant
      complementary feeding. METHODS: In 2003 a cross-sectional study was conducted of
      mother-and-infant pairs in Switzerland. The mothers, randomly chosen by local
      community mother-and-child health services, completed a 24-h dietary recall
      questionnaire and reported the infant's age at the first introduction of various
      foods. Descriptive analysis, group testing and regression analysis of data
      collected were conducted. RESULTS: Introduction of solids mainly occurred between
      the 5th and 6th months. Five per cent of the mothers introduced complementary
      food before the age of 4 mo. The main influencing factors for infant feeding were
      maternal age, language regions, mother's BMI and smoking status, the presence of
      siblings, and an allergic predisposition of the infant. CONCLUSION: The timing of
      the introduction of complementary foods meets with Swiss guidelines. WHO
      recommendations, however, are not met. This may be due to a misunderstanding of
      the Swiss Paediatric Association's age-range recommendations or insufficient
      promotion of the WHO recommendations.

PMID- 16801179
TI  - Case-control study of breast milk calcium in mothers of children with and without
      nutritional rickets.
AB  - AIM: Despite similarly low calcium intakes and normal vitamin D status, only some
      Nigerian children develop nutritional rickets. We hypothesized that mothers with
      children who had developed rickets might have lower breast-milk calcium
      concentration than mothers with normal children and compared the breast-milk
      calcium concentration of mothers who had had children with rickets with those who
      had not (controls). METHODS: We collected breast milk from 35 Nigerian mothers
      who had previously had children with nutritional rickets. For each case mother,
      we collected breast milk from three matched control mothers at the same stage of
      lactation (+/-4 weeks) who had had no children with rickets. Data were collected
      about parity, stage of lactation, and the infant's intake. The mother's bone
      density was measured. RESULTS: The mean breast milk calcium concentration of
      mothers of children with rickets (4.30+/-1.24 mmol/L) was less than that of
      control mothers (4.65+/-1.03 mmol/L; P=0.034 in multivariate regression
      controlling for duration of lactation and resumption of menses). Forearm bone
      mineral content was significantly related to breast milk calcium concentration
      (r=0.20) after adjusting for height, weight, and bone area (P=0.028). CONCLUSION:
      Reduced breast-milk calcium concentration may contribute to a reduced calcium
      intake in infancy and predispose children to nutritional rickets.

PMID- 16801180
TI  - Non-alcoholic fatty liver disease in obese children evaluated by magnetic
      resonance imaging.
AB  - AIM: To investigate the prevalence of non-alcoholic fatty liver disease (NAFLD)
      in a group of obese children (BMI > 97th %) and to establish correlations between
      the severity of hepatic fatty infiltration, auxological findings and parameters
      of insulin resistance. METHODS: 44 obese children, aged 6-16 years, with a BMI
      above the 97th centile were selected for analysis. Hepatic fat content was
      assessed by phase contrast MRI. Demographic data included weight, height, body
      mass index, body fat mass and waist circumference. Blood tests included fasting
      blood glucose, fasting insulin and lipid profile. Insulin sensitivity was
      evaluated with QUICKI. RESULTS: Elevated hepatic fat fraction (FF) was identified
      in 14 subjects (31.8%; 0.07 SEM). Children with fatty liver (FF > 9%) had higher
      ALT (P<0.0001), AST (P=0.002) and triglycerides (P=0.008) values compared to the
      children without NAFLD. All the children showed a decreased insulin sensitivity
      (P<0.0001), but no difference was found between children with or without NAFLD.
      The degree of liver fatty infiltration was positively correlated with ALT
      (P<0.0001), AST (P<0.002) and gammaGT (P<0.0001), with height (P<0.006) and BMI
      (P<0.05) but not with estimates of body fat mass or fat distribution. CONCLUSION:
      Obese children are frequently affected by NAFLD, which cannot be predicted by
      clinical and/or anthropometrical findings. There is however a strict correlation
      between the degree of liver fatty infiltration and elevation of liver enzymes.

PMID- 16801181
TI  - Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction in
      the diagnosis of biliary dyskinesia in children.
AB  - AIM: Biliary dyskinesia (BD) is characterized by symptoms of biliary disease, no
      evidence of gallstones on ultrasonography (USG), and diminished gallbladder
      ejection fraction. The diagnosis is based on findings of abnormal gallbladder
      ejection fraction diagnosed by hepatobiliary scintigraphy before and after
      stimulation of gallbladder contraction with cholecystokinin (CCK). We used an
      easier diagnostic technique defined as ultrasonographic evaluation of fatty meal
      stimulated gallbladder contraction, employing USG with the diagnosis of biliary
      dyskinesia in children. The study was conducted by USG to investigate the volume
      and contractility of the gallbladder (GB) in fasting conditions and 45 min after
      a standardized fatty meal (SFM) in normal children and in a group of BD patients,
      and to compare the diagnostic value of this test with scintigraphy and to
      evaluate its use as a new method in the diagnostic algorithm of BD. METHODS: We
      assessed the volume changes and contractility of the GB in response to SFM by USG
      in 14 patients with BD diagnosed by cholecystokinin stimulated hepatobiliary
      scintigraphy (CCKs-HBS); and compared them with 14 control patients matched for
      age and gender before cholecystectomy. After an overnight fasting, GB volume was
      measured by USG then the GB volume was again measured after the SFM ingestion.
      Using USG, length, width and height of GB were measured, and volume of the GB was
      calculated using the 'Dodds' formula. These volume measurements were used to
      calculate the percentage of gallbladder emptying (ejection fraction). Fasting,
      after SFM and EF values comparisons between groups were done with student's t
      test. RESULTS: No statistically significant difference of fasting GB volumes were
      demonstrated between BD and control groups (14.1+/-6.7 cm3 and 13.4+/-4.0 cm3
      respectively). GB volumes of the BD group after SFM were significantly greater
      than in healthy controls (13.1+/-1.8 cm3 and 3.4+/-0.9 cm3 respectively,
      P<0.0005). The calculated percentage of gallbladder contraction (ejection
      fraction) was found to be lower in BD patients than in healthy controls (7.1%+/
      1.8% and 73.8%+/-6.4%, respectively, P<0.0005). CONCLUSION: Ultrasonographic
      evaluation of fatty meal stimulated gallbladder contraction provides relatively
      reliable and reproducible results. Thus it can be used for scanning in patients
      with biliary symptoms as a prior modality to CCK-HBS since it is a relatively
      easier, safer and available method with which to make a definitive diagnosis of
      BD. The patients with symptoms of biliary disease and no evidence of gallstones
      on USG should be evaluated by the method proposed in this study before the
      routine laboratory and radiologic tests.

PMID- 16801182
TI  - Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal
      transport in preterm infants.
AB  - AIM: To investigate whether a mixture of prebiotic non-digestible
      oligosaccharides (GosFos; referring to galacto- and fructo-oligosaccharides)
      would improve feeding tolerance in preterm infants on full enteral formula
      feeding. We hypothesized that GosFos would: (1) reduce stool viscosity and (2)
      accelerate gastrointestinal transport. METHODS: In a placebo-controlled double
      blind trial 20 preterm infants on full enteral nutrition (gestational age 27 (24
      31) weeks, postnatal age 42 (11-84) days, and weight at study entry 1570 (1080
      2300) g were randomly allocated to have their feedings supplemented with either
      GosFos (1 g/100 mL) or placebo for 14 days. Stool viscosity was measured by high
      pressure capillary rheometry. Gastrointestinal transport time was assessed as the
      time from feeding carmine red to its appearance in the diaper. The hypotheses
      were tested as a priori ordered hypotheses. Data are shown as median (range).
      RESULTS: Birth weight, gestational age, postnatal age, and weight at study entry
      did not differ between groups. GosFos significantly reduced both stool viscosity,
      as measured by extrusion force (32 (2-67) versus 158 (24-314) N), and
      gastrointestinal transit time (12 (4-33) versus 26 (5-52) h). No adverse effects
      were observed. CONCLUSION: Formula supplementation with GosFos reduced stool
      viscosity and accelerated gastrointestinal transport. Further trials are required
      to investigate whether GosFos facilitates enteral feeding advancement and early
      enteral nutrition thereby eventually reducing the incidence of catheter-related
      nosocomial infections and improving long-term outcome.

PMID- 16801183
TI  - Analysis of renal biopsies performed in children with abnormal findings in
      urinary mass screening.
AB  - BACKGROUND: School urinary mass screening tests are performed to make early
      diagnosis and provide proper treatment for chronic renal diseases. However, very
      few systemic analyses or studies have been reported regarding final diagnosis
      made on children with abnormal urinary screening results. AIM: To study the cases
      of renal biopsy in children detected in urinary screening. METHODS: We
      retrospectively analysed 461 cases of renal biopsy performed on children referred
      to us with abnormal school urinary mass screening results who satisfied
      indications for renal biopsy. RESULTS: Pathologically abnormal findings were
      observed in 285 (61.8%) patients. Thin glomerular basement membrane disease was
      detected in 127 (27.5%) cases and IgA nephropathy in 121 (26.2%) cases. Among
      those 461 children, microscopic haematuria was observed in 289 (62.7%) patients,
      proteinuria in nine (2.0%), and both in 163 (35.4%). In addition, a statistically
      higher rate of pathological abnormalities on renal biopsy was noted in the group
      with microscopic haematuria combined with proteinuria and also in cases with more
      severe haematuria. CONCLUSION: School urinary mass screening has greatly
      contributed to diagnosing chronic renal diseases. Continuous medical observation
      is required when abnormal urinalysis is observed, and a more aggressive medical
      approach such as renal biopsy should also be performed if necessary.

PMID- 16801184
TI  - Serum neopterin levels in children with primary nephrotic syndrome.
AB  - AIM: To assess the changes that occurs in serum neopterin levels in children with
      primary nephrotic syndrome. METHODS: Serum neopterin levels were measured by
      ELISA in 38 children with active primary nephrotic syndrome (group I) and 17
      children with primary nephrotic syndrome in remission (group II) and 20 healthy
      controls. All patients had normal creatinine clearance. Among group I, 28
      patients were steroid-sensitive while 10 patients were steroid-resistant.
      RESULTS: Serum neopterin levels were significantly elevated in group I patients
      (median = 30, 7.2-43.2 nmol/l) compared with group II (median = 6, 2-10 nmol/l,
      P<0.001) and controls (median = 3.2, range: 0.4-1.8 nmol/l, P<0.001). Group II
      patients had similar neopterin levels compared with controls (P=0.71). There was
      a significant positive correlation between serum neopterin levels and the degree
      of proteinuria in group I patients (r = 0.4, P=0.01). No significant differences
      in serum neopterin levels were noted between steroid-sensitive and steroid
      resistant patients (P=0.4). CONCLUSION: Serum neopterin could be used as a marker
      of the activity of primary nephrotic syndrome but it could not be used to
      differentiate between steroid-sensitive and steroid-resistant patients.

PMID- 16801185
TI  - Effects of cyclosporine A in hyperzincaemia and hypercalprotectinaemia.
AB  - INTRODUCTION: Hyperzincaemia and hypercalprotectinaemia with systemic
      inflammation, recurrent infections, hepatosplenomegaly, arthritis, anemia,
      cutaneous inflammation, and failure to thrive is an extremely rare disease and no
      therapy is reported. AIM: To evaluated the effects of cyclosporine A in
      hyperzincaemia and hypercalprotectinaemia in terms of serum cytokine level
      changes before and after treatment. METHODS: A 10-year-old girl was admitted
      suffering from pyoderma gangrenosum, hepatosplenomegaly, anemia that was
      unresponsive to iron supplementation, persistent inflammation, arthritis, and
      increased serum zinc. The level of serum calprotectin was extremely high;
      therefore, we diagnosed hyperzincaemia and hypercalprotectinaemia and started
      cyclosporine A treatment. Twelve cytokines in serum were measured before and one
      year after treatment. RESULTS: Cyclosporine A was very effective. Her skin lesion
      and joint pain were alleviated and quality of life was markedly improved. C
      reactive protein had decreased and anemia had improved. While zinc levels had
      fallen, calprotectin remained at an extremely high level. Of the cytokines
      examined, interleukin -6 serum levels had fallen and interleukin -8 showed a
      marked reduction after treatment. CONCLUSION: Cyclosporine A is effective for
      hyperzincaemia and hypercalprotectinaemia. Serum interleukin -8 may be useful in
      assessing the therapeutic effects of cyclosporine A in hyperzincaemia and
      hypercalprotectinaemia.

PMID- 16801186
TI  - Partial cerebellar hypoplasia in a patient with Prader-Willi syndrome.
AB  - We report a 3-y-old male infant with Prader-Willi syndrome (PWS) caused by a de
      novo interstitial deletion of 15q11-q13. Additional features included a right
      cerebellar hemisphere hypoplasia. The extent of deletion was determined by FISH
      analysis using an SNRPN PW/AS probe that maps in the PWS/AS critical region (CR)
      and with specific 15q BACs. We unravelled an interstitial 15q11.2-q13.1 deletion
      spanning about 3 Mb. CONCLUSION: To date only a few other PWS patients--including
      autopsy cases--with CNS structural anomalies have been described. Our case report
      adds knowledge to the issue of brain involvement in Prader-Willi syndrome.
      Further MRI studies of PWS patients will be helpful to clarify a correlation
      between PWS and brain abnormalities.

PMID- 16801187
TI  - Fetal stroke and congenital parvovirus B19 infection complicated by activated
      protein C resistance.
AB  - Parvovirus B19 infection in gestation has been associated with severe fetal
      complications such as anaemia, hydrops and fetal demise. Fetal infection in the
      first trimester poses the greatest risk for these complications, but infection
      during the third trimester is more common than previously appreciated and can be
      associated with severe complications, i.e. fetal death, in the absence of hydrops
      or classical clinical symptoms. Parvovirus B19 infection has been associated with
      vasculitis and pathological changes in the central nervous system, which may
      cause stroke. We report a newborn infant with a rare combination of a recent
      central nervous system infection with parvovirus B19 and a factor V Leiden
      mutation, who developed fetal stroke. CONCLUSION: Factor V Leiden mutation leads
      to activated protein C resistance and increases the risk of thromboembolism.
      Thromboembolism occurs rarely in newborns with activated protein C resistance,
      but can be precipitated by dehydration, asphyxia and infection. Although
      parvovirus B19 infection of the central nervous system may be a precipitant in
      neonatal and/or fetal stroke, it can also cause stroke independent of a
      thrombophilic mutation. In this case, both causative factors may have coincided.

PMID- 16801188
TI  - Respiratory tract malacia: possible cause of sudden death in infancy and early
      childhood.
AB  - AIM: To stress the importance of considering Laryngo-tracheo-bronchomalacia
      (LTBM) as a cause of death in infancy and early childhood. METHODS: A case of
      Tracheo-bronchomalacia diagnosed at autopsy is presented, with a short review of
      the literature. RESULTS: The condition causes functional weakness of the airways
      due to congenital or acquired abnormalities of airway cartilage. The etiology of
      the congenital variant is uncertain; the acquired may be caused by localized
      external pressure. Morphologically, cartilage rings are shorter and softer than
      normal, causing collapse, especially during forced expirations. The defect can be
      an isolated finding, but there are a number of associations with other
      malformations. LTBM may be misdiagnosed as asthma. Symptoms include wheezing,
      barking cough, frequent respiratory infections and cyanotic episodes. Treatment
      might be conservative or include surgery, depending on etiology and severity.
      CONCLUSION: Laryngo-tracheo-bronchomalacia (LTBM) is usually not considered a
      sufficient cause of death in infancy and early childhood, but airway malacia may
      be an unrecognized cause of sudden death in infancy and early childhood, and
      should be considered, especially in cases where there is a history of respiratory
      distress.

PMID- 16801189
TI  - Identification of the 5T-12TG allele of the cystic fibrosis transmembrane
      conductance regulator gene in hypertrypsinaemic newborns.
AB  - In order to increase knowledge of the pathogenic effect of the 5T-12TG allele of
      the cystic fibrosis transmembrane conductance regulator (CFTR) gene, we evaluated
      its presence in 24 hypertrypsinaemic newborns with borderline sweat tests. Among
      20 CFTR-identified alterations, the 5T-12TG haplotype was the second most
      frequent mutation (14.6%) over F508del. CONCLUSION: Our study suggests the need
      for searching for this allele in hypertrypsinaemic infants with inconclusive
      sweat tests.

PMID- 16801190
TI  - Hypoglycaemia and seizures in large-for-gestational-age (LGA) full-term neonates.
AB  - AIM/METHODS: To assess the risk of hypoglycaemia-associated seizures in large-for
      gestational-age (LGA) full-term neonates data from the Netherlands Perinatal
      Registry were analysed. RESULTS: From 1997 to 2002 hypoglycaemia was recorded in
      1513 of 9318 (16.2%) admitted LGA (defined as birthweight > or = 97.7 percentile)
      full-term neonates without maternal diabetes, of whom 20 (1.3%) had seizures. In
      six of these 20, hypoglycaemia was the single cause of seizures. CONCLUSION:
      Symptomatic hypoglycaemia occurs in healthy LGA full-term neonates.

PMID- 16801191
TI  - The anal position index: a simple method to define the normal position of the
      anus in neonate.
AB  - AIM: The purpose of this study was to determine the normal position of anus using
      anal position index (API) and the modified measurement method and to emphasize
      the importance of ectopic anus. This cross-sectional study was performed on 400
      neonates equally, boys and girls who were all delivered at full term without any
      malformations. Anal position index, which is the ratio of anus-fourchette
      distance in girls and anus-scrotum distance in boys to the distance between
      coccyx and fourchette/scrotum, was calculated in all cases. To make correct
      measurements, transparent adhesive tape was used longitudinally on midperinum in
      a way that it covered the anus. Then fourchette/scrotum, anus center and the
      lower margin of coccyx were marked on it. Distances marked on each tape were then
      measured with the standard ruler. Mean+/-SD of API in girls was 0.45+/-0.08 (95%
      CI: 0.44-0.46) and in boys 0.54+/-0.07 (95% CI: 0.53-0.55). Mean+/-2 SD was
      considered as the normal range for an anus position. Six female and five male
      neonates who had abnormal APIs were investigated further. CONCLUSIONS: Our
      findings suggested a simple method for determination of normal position of anus
      in children, especially those who are referred for chronic constipation. API can
      never be considered as the sole indication for the surgical intervention.

PMID- 16801192
TI  - Case 1: External ear anatomic anomaly in a newborn.

PMID- 16801193
TI  - Case 2: Two young children with polydipsia, polyuria and severe hypertension.

PMID- 16801194
TI  - Rectal sunflower seed bezoar.

PMID- 16801195
TI  - Growth acceleration in prepubertal obese children: role of hyperinsulinaemia.

PMID- 16801196
TI  - Barium-associated appendicitis in a childhood case with Crohn's disease.

PMID- 16801197
TI  - Infantile erythema multiforme following hepatitis B vaccine.

PMID- 16801198
TI  - A case of Shwachman-Diamond syndrome in a male neonate.

PMID- 16801201
TI  - Rehabilitation medicine in Croatia -- sources and practice.
AB  - Sources of rehabilitation medicine, the need for rehabilitation and its practice
      in Croatia were studied, based on available data. The study revealed that current
      practice has advanced since the country's independence, but that there are many
      shortcomings; adequate care is not provided to all who could benefit from it, and
      there is wastage of resources.

PMID- 16801202
TI  - Does fascicular neurotomy have long-lasting effects?
AB  - OBJECTIVE: To determine whether fascicular neurotomy has long-lasting effects on
      spasticity. DESIGN: We present 4 clinical cases and a critical analysis of the
      literature. PATIENTS: This is a retrospective study on 4 patients referred to our
      department for spastic equinovarus foot deformity. For all 4, neurotomy was
      successful not long after surgery, but spasticity reappeared after a few months.
      METHODS: We compared our results with those in the PubMed database. RESULTS: Most
      publications acknowledge the immediate effectiveness of this surgery, but do not
      study the long-term effects of neurotomy. No publication proved long-lasting
      effects of neurotomy for spastic equinovarus foot deformity. The only long-term
      follow-up with a sufficient population is the one of Berard et al. who reported
      61% recurrence. CONCLUSION: There is no study showing that tibial nerve neurotomy
      has long-lasting effects. The 4 cases reported are an illustration that
      recurrence of spasticity may occur after neurotomy. These findings have to be
      taken into account for treatment decision-making and for provision of information
      to patients.

PMID- 16801203
TI  - Predicting mobility outcome one year after stroke: a prospective cohort study.
AB  - OBJECTIVE: To develop a prognostic model to predict mobility outcome one year
      post-stroke. DESIGN: Prospective cohort study in patients with a first-ever
      stroke admitted for inpatient rehabilitation. PATIENTS: A total of 217 patients
      with stroke (mean age 58 years) following inpatient rehabilitation in 4
      rehabilitation centres across the Netherlands. METHODS: Mobility was measured
      using the Rivermead Mobility Index at one year poststroke. Included independent
      variables were: patient and stroke characteristics, functional status, urinary
      incontinence, sitting balance, motor and cognitive function. Univariate and
      multivariate linear regression analyses were performed in a model-developing set
      (n=174) and the model was validated in cross-validation set (n=43). RESULTS:
      Total Rivermead Mobility Index score at one year post-stroke was predicted by
      functional status, sitting balance, time between stroke onset and measurement,
      and age. The derived model predicted 48% of the variance, while validation in the
      cross-validation set resulted in an adjusted R(2) of 0.47. CONCLUSION: The
      present prospective study shows that outcome of mobility one year after stroke
      can be predicted validly by including functional status, sitting balance, moment
      of admission to the rehabilitation centre after stroke onset and age.

PMID- 16801205
TI  - Use of healthcare, patient satisfaction and burden of care in Guillain-Barre
      syndrome.
AB  - OBJECTIVE: The aim of this study was to investigate, in an unselected sample of
      patients with Guillain-Barre syndrome in Sweden, the utilization of healthcare
      resources, satisfaction with these resources, informal help and the burden of
      care on family caregivers during the first 2 years after onset. SUBJECTS: Forty
      four patients were enrolled from 8 hospitals, and 42 of them were followed for 2
      years. METHODS: Data on the utilization of hospital inpatient and outpatient
      care, primary care and community-based services were collected via computerized
      registry information, medical records and a specific protocol. Patient
      satisfaction and the burden on family caregivers were studied using
      questionnaires. RESULTS: Forty-one patients required inpatient hospitalization
      for a mean of 82 days. Patients with persistent dependency during activities of
      daily living had significantly longer hospital stays and more days of outpatient
      rehabilitation. The majority of patients were satisfied with their care, but
      dissatisfaction was found regarding information and finances. At 2 years after
      onset, 26% of patients still depended on informal help. The spouses expressed
      increased concern and responsibility for household and family. CONCLUSION:
      Patients with persistent disability due to Guillain-Barre syndrome were found to
      have long-term need for services from the healthcare system and informal help.

PMID- 16801204
TI  - Motor performance in physically well-recovered men with traumatic brain injury.
AB  - OBJECTIVE: The primary aim of this study was to compare the motor performance of
      physically well-recovered men with traumatic brain injury with that of healthy
      men. DESIGN: Cross-sectional study in a national rehabilitation centre. METHODS:
      Static and dynamic balance, agility and rhythm co-ordination of men with
      traumatic brain injury (n=34) and healthy controls (n=36) were assessed. Between
      group differences in dynamic balance and agility were analysed by analysis of
      covariance and differences in static balance and rhythm co-ordination by logistic
      regression analysis. Cut-off points for clinical screening were determined by
      receiver operating characteristics analyses. RESULTS: Men with traumatic brain
      injury had impaired balance and agility compared with healthy men and in a rhythm
      co-ordination test they had difficulties in starting and sustaining simultaneous
      rhythmical movements of hands and feet. In receiver operating characteristics
      analyses a running figure-of-eight test (agility), tandem walking forwards
      (dynamic balance) and rhythm co-ordination test with fast tempo were found the
      most sensitive and specific for distinguishing between men with traumatic brain
      injury and the healthy men. CONCLUSIONS: The impairments in motor performance of
      physically well-recovered patients with traumatic brain injury were obvious. The
      results of this study extend the knowledge of problems in motor performance among
      patients with traumatic brain injury and provide further information for clinical
      rehabilitation.

PMID- 16801206
TI  - Measuring patient-reported outcomes after discharge from inpatient rehabilitation
      settings.
AB  - OBJECTIVE: To examine the sensitivity of the Short Form Activity Measure for Post
      Acute Care (AM-PAC) in comparison to the Functional Independence Measure (FIM)
      across a 12-month period after discharge from rehabilitation hospital. DESIGN:
      Prospective longitudinal study. Patients were recruited while receiving inpatient
      services from facilities in the north-east USA and interviewed 1, 6 and 12 months
      thereafter. PATIENTS: Convenience sample of 516 patients at baseline (65%
      retention at the final follow-up) receiving rehabilitation services for
      neurological, lower extremity orthopedic, or complex medical conditions. Mean age
      68.3 years; 47% male. MAIN OUTCOME MEASURES: AM-PAC Physical and Movement,
      Personal Care and Instrumental, and Applied Cognitive Activity scales; FIM Motor
      and Cognitive scales. RESULTS: All 3 AM-PAC scales were sensitive to both
      positive and negative change across the follow-up period. Standardized response
      means for the AM-PAC were consistently larger than for the FIM across patient and
      severity groups. A greater percentage of patients showed positive change that
      exceeded the minimal detectable change on the AM-PAC than on the FIM both 6- and
      12-month follow-ups. CONCLUSION: The short-form AM-PAC scales are more sensitive
      measures of change in functional activity performance over time in the general
      population of persons who receive inpatient rehabilitation services compared to
      the FIM. Thus, the AM-PAC offers a short, comprehensive, and sensitive measure of
      positive and/or negative change in patients' ability to perform important
      activities of daily life.

PMID- 16801207
TI  - Correlation between impairment and motor performance during reaching tasks in
      subjects with spastic hemiparesis.
AB  - OBJECTIVE: The main purposes of this study were to examine, in subjects with
      chronic hemiparesis following a stroke: (i) the correlations between tests of
      muscle tone, stiffness, spasticity, paresis and co-contraction, and (ii) the
      correlations of these tests and measurements of impairment to upper extremity
      motor performance. DESIGN: Prospective, cross-sectional, correlation matrix using
      sample of convenience. SUBJECTS: Thirteen subjects with chronic hemiparesis
      secondary to a cerebrovascular accident (stroke) were tested. METHODS: Subjects
      were assessed using the Fugl-Meyer Upper Extremity Motor Assessment, modified
      Ashworth scale, deep tendon reflexes, and muscle characteristics that included
      quantification of muscle stiffness, paresis and co-contraction during a voluntary
      reaching task and during passive movements. Surface electromyographic and
      myotonometric muscle stiffness data were obtained during movement trials.
      RESULTS: Biceps and triceps brachii muscle paresis and excess biceps brachii co
      contraction during voluntary reaching had the highest correlations to decreased
      motor performance. Muscle tone measurements did not have significant correlations
      to upper extremity performance. CONCLUSION: Paresis of elbow flexors and
      extensors and excess co-contraction of the biceps brachii during voluntary
      reaching appear to be most predictive of upper extremity motor performance.
      Results are discussed in relation to the specific challenges these findings pose
      for spastic paresis clinical management.

PMID- 16801208
TI  - Symptoms, clinical and physiological findings motivating home mechanical
      ventilation in patients with neuromuscular diseases.
AB  - OBJECTIVE: To clarify the relationship between symptoms, clinical signs and
      physiological abnormalities that were motivating the initiation of home
      mechanical ventilation in patients suffering from neuromuscular diseases.
      METHODS: From The Swedish Home Mechanical Ventilation Register we identified 352
      patients with neuromuscular diseases and we looked at circumstances (acute vs
      elective) and clinical motives for starting ventilatory support. RESULTS: Home
      mechanical ventilation was commenced electively in 268 patients (76%) and among
      these daytime sleepiness was the most common motive, being reported in 56% of the
      patients. In the 24 children with spinal muscular atrophy, however, 96% started
      ventilation electively and cough insufficiency was the most common motive. The
      patients were moderately hypercapnic (PaCO(2): 7.0 kPa, SD 1.3). None of the
      clinical motives were related to the PaCO(2) level. Average PaO(2) was above 8
      kPa in all groups, but lowest in the patients with post-polio and dystrophia
      myotonica. Mean vital capacity was close to 40% of predicted, but significantly
      lower in the Duchenne patients (26% of predicted). CONCLUSION: Daytime sleepiness
      was the most common clinical symptom motivating home mechanical ventilation in
      this group of patients with chronic hypercapnic respiratory insufficiency
      secondary to neuro/myopathies. Respiratory function testing is therefore
      suggested to be included in the diagnostic work up of daytime sleepiness in these
      patients.

PMID- 16801209
TI  - What is "the good back-consultation"? A combined qualitative and quantitative
      study of chronic low back pain patients' interaction with and perceptions of
      consultations with specialists.
AB  - OBJECTIVE: To identify core elements of what patients with chronic low back pain
      perceive as good clinical communication and interaction with a specialist ("The
      Good Back-Consultation"). DESIGN: Qualitative study including observation of
      consultations and a subsequent patient interview. Quantitative data were also
      recorded. SUBJECTS: Thirty-five patients with chronic low back pain referred to a
      specialist. METHODS: Thirty-five consultations were observed with respect to
      history-taking, clinical examination and interaction between patient and doctor.
      Patients were subsequently interviewed about how they perceived the consultation.
      Fourteen specialists with various specialty branches and 35 patients (18 males)
      participated. For 3 of the specialists a positive effect (return to work) on
      patients with chronic low back pain had been documented in previous randomized
      controlled trials. Qualitative data analysis was performed using a template
      method. RESULTS: Most patients thought that the history-taking and clinical
      examination had been thorough and satisfactory. Patients emphasized the
      importance of being given an explanation during the examination of what was being
      done and found, of receiving understandable information on the causes of the
      pain, of receiving reassurance, discussing psychosocial issues and discussing
      what can be done. The most important characteristic of "The Good Back
      Consultation" was that the specialist took the patient seriously. CONCLUSION: The
      findings may represent an important potential for enhancing clinical
      communication with patients.

PMID- 16801210
TI  - Development of a clinical examination in non-specific low back pain: a Delphi
      technique.
AB  - OBJECTIVE: To establish the discriminatory items of the clinical examination of
      non-specific low back pain, important to physiotherapists. DESIGN: A focus group
      and Delphi technique with UK physiotherapists. SUBJECTS: A purposive sample of 30
      physiotherapists attended a focus group and completed 3 rounds of Delphi
      questionnaires. METHODS: Data were analysed using mixed qualitative and
      quantitative approaches. A frequency content analysis identified commonly
      identified tests and questions, whilst the Delphi consensus technique assumed
      consensus had been reached with greater than 80% agreement on item inclusion or
      exclusion. RESULTS: The focus group established the structure of the clinical
      examination with 15 domains of questioning or physical testing. Three rounds of
      Delphi questionnaires established the important items of the clinical
      examination. The list of tests and questions included items evaluating both the
      psychosocial and biomedical status of the patient as well as questions screening
      for red flags. CONCLUSION: This is the first work to establish discriminatory
      tests in the clinical examination of non-specific low back pain, important to
      physiotherapists. The clinical examination will subsequently be evaluated for
      item validity and data will undergo cluster analysis. The items of this clinical
      examination may provide evidence for the existence of homogenous sub-groups
      within the heterogeneous non-specific low back pain diagnosis.

PMID- 16801211
TI  - Marma therapy for stroke rehabilitation -- a pilot study.
AB  - OBJECTIVE: To examine feasibility and acceptability issues and to gather
      preliminary outcome data to ascertain the numbers needed for a trial of Marma
      massage therapy for stroke rehabilitation. DESIGN: Pilot non-randomized
      controlled trial, comparing standard care with standard care plus Marma therapy
      in post-stroke patients with a nested qualitative study. PARTICIPANTS: Adult
      patients who had an infarction or haemorrhage at any brain location with a
      Barthel Index score of 75/100 or less. METHODS: Feasibility was assessed in terms
      of recruitment and response rates and loss to follow-up, and acceptability was
      assessed by patient interviews (n=13). The main outcome measure was the Barthel
      Index. RESULTS: The recruitment rate was 0.53 patients per week in a stroke unit
      with an admission rate of 15.1 per week, the response rate was 91% and the loss
      to follow-up 30%. Most patients believed that the massage was beneficial, and
      although some reported pain, all interviewed would choose it again. The
      effectiveness data showed no significant differences in changed scores. However,
      the secondary measure follow-up score differences of the Motricity Index at 6 and
      12 weeks and the trunk control test at 6 weeks suggest a possible greater
      improvement in the intervention group (p<0.05, p<0.01). CONCLUSION: There are
      grounds for a future trial of Marma therapy (n=172), which would be feasible and
      acceptable to patients.

PMID- 16801213
TI  - Putative dual role of ephrin-Eph receptor interactions in inflammation.
AB  - Inflammation is associated with a decreased adhesion between endothelial cells in
      blood vessels and an increased adhesion of circulating leukocytes to vascular
      endothelium and to epithelia of internal organs. These changes lead to leukocyte
      extravasation and tissue transmigration. We propose that ephrins and Eph
      receptors play important, but underappreciated, signaling roles in these
      processes. At early stages of inflammation, EphA2 receptor and ephrin-B2 are
      overexpressed in endothelial and epithelial cells, thus leading to those events
      (expression of adhesion molecules on the cell surface and reorganization of the
      intracellular cytoskeleton) that cause cell repulsion and disruption of
      endothelial and epithelial barriers. At later stages of inflammation, expression
      of EphA1, EphA3, EphB3, and EphB4 on leukocytes and endothelial cells decreases,
      thus promoting adhesion of leukocytes to endothelial cells. Taking into
      consideration the abundance of ephrins and Eph receptors in tissues and the
      robustness of their signaling effects, the proposed involvement is likely to be
      substantial and may constitute a novel therapeutic target.

PMID- 16801214
TI  - Radiation-induced lysosomal iron reactivity: implications for radioprotective
      therapy.
AB  - A novel mechanism of radiosensitization involves radiation-enhanced autophagy of
      damaged mitochondria and various metalloproteins, by which iron accumulates
      within lysosomes. Hydrogen peroxide, formed by the radiolytic cleavage of water,
      generates in the presence of lysosomal redox-active iron extremely reactive
      hydroxyl radicals by Fenton-type chemistry. Subsequent peroxidative damage of
      lysosomal membranes initiates release of harmful content from ruptured lysosomes
      that triggers a cascade of events eventuating in DNA damage and apoptotic or
      necrotic cell death. This article reviews the role of lysosomal destabilization
      in radiation-induced cell damage and death. The potential effects of iron
      chelation therapy targeted to the lysosomes for protection of normal tissues
      against unwanted effects by radiation is also discussed.

PMID- 16801212
TI  - Hyperglycemia and glucosamine-induced mesangial cell cycle arrest and
      hypertrophy: Common or independent mechanisms?
AB  - The Hexosamine Pathway (HP) is one hypothesis proposed to explain glucose
      toxicity and the alterations observed during the course of diabetic microvascular
      complication development. Glucosamine is a precursor of UDP-N-Acetylglucosamine
      (UDP-GlcNAc), the main product of the HP that has often been used to mimic its
      activation. The transfer of a UDP-GlcNAc residue onto proteins (O-GlcNAc
      modification) represents the final step of the HP and is considered as a major
      mechanism by which this pathway exerts its signalling effects. While it is well
      accepted that the HP promotes extracellular matrix accumulation in the context of
      diabetic nephropathy, its involvement in the perturbations of cell cycle
      progression and hypertrophy of renal cells has been poorly investigated.
      Nevertheless, in a growing number of studies, the HP and O-GlcNAc modification
      are emerging as important regulators of cell cycle progression. This review will
      focus on the role of glucosamine and O-GlcNAc modification in cell cycle
      regulation in the context of diabetic nephropathy. Special emphasis will be given
      into the role of the HP as a potential mediator of the effects of high glucose on
      the perturbations of renal cell growth.

PMID- 16801215
TI  - Mitochondrial AZT metabolism.
AB  - AZT remains an important drug to combat HIV infection in combination with other
      nucleoside analogs. However, long-term treatment with nucleoside analogs can
      result in mitochondrial toxicity, which can be fatal in some forms. We review the
      metabolic pathway for AZT transport and phosphorylation within mitochondria and
      its interaction with the mitochondrial DNA polymerase, Pol-gamma. Suggested
      mechanisms for the mitochondrial toxicity of AZT related to this metabolism are
      discussed. Finally we review recent evidence that the HIV virus itself is
      involved in the toxicity of AZT.

PMID- 16801216
TI  - Pannexin: to gap or not to gap, is that a question?
AB  - Vertebrates express two families of gap junction proteins: the well characterized
      connexins and the recently discovered pannexins. The latter are related to
      invertebrate innexins. Here we present the hypothesis that pannexins, rather than
      providing a redundant system to gap junctions formed by connexins, exert a
      physiological role as nonjunctional membrane channels. Specifically, we propose
      that pannexins can serve as ATP release channels. This function presumptively is
      also performed by innexins in invertebrates, in addition to their traditional gap
      junction role.

PMID- 16801217
TI  - Heterogeneity of Escherichia coli-expressed human muscle creatine kinase.
AB  - Creatine kinase (CK) plays an important role in maintaining a constant ATP:ADP
      ratio during periods of high energy usage. Elevated levels of CK give an early
      indication of myocardial infarction. The enzyme has four major isozymes with
      heterogeneity being observed for each of them. In many cases the source of the
      heterogeneity is unclear. However, some of the isoforms are known to result from
      exposure to serum proteases, and analysis of the plasma isoforms provides an
      estimate of the time of onset of the infarction. Somewhat surprisingly,
      isoelectric focusing (IEF) experiments provided evidence of heterogeneity in
      human muscle CK (HMCK) expressed in E. coli. To investigate this further, HMCK
      was purified to apparent homogeneity utilizing Blue Sepharose affinity
      chromatography and HiPrep Q anion exchange chromatography. Additional
      purification on a PBE 94 chromatofocusing column resulted in four fractions,
      three of which, HMCK I - III, were characterized. The three isoforms are all
      active and have similar kinetic parameters. They exhibited identical bands on SDS
      PAGE but different anodal mobility on non-denaturing gels. Modification of C
      terminal and/or cysteine residues has been ruled out, and deamidation of
      asparagine or glutamine residue(s) is proposed to be the cause of isoform
      formation. In addition each of these isoforms showed a similar four-band pattern
      on a carrier ampholytes-based IEF gel. Two-dimensional IEF analysis showed that
      an equilibrium was established between the four bands, suggesting that the four
      components were unstable and generated only when the protein was subjected to
      IEF.

PMID- 16801218
TI  - Effects of cyclosporin A, FK506 and rapamycin on calcineurin phosphatase activity
      in mouse brain.
AB  - Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase expressed at high
      levels in brain. The immunosuppressive drugs cyclosporin A and FK506, but not
      rapamycin are specific inhibitors of calcineurin, the inhibitory effects of which
      have been elucidated in the immune system. Here by using these compounds as
      inhibitors, we assayed the enzyme in mouse brain after injection of 12.5 nmol
      cyclosporin A, FK506, or rapamycin into the left lateral ventricle of mouse
      brain. Data from calcineurin activity assay suggest that infusion of cyclosporin
      A or FK506, rather than rapamycin inhibited calcineurin activity in brain and in
      a substrate noncompetitive manner, which is revealed by the in vitro enzyme
      kinetic analysis. Cyclosporin A or FK506 injected into brains also affected the
      inhibitory effects of cyclosporin A or FK506 added to brain extracts on
      calcineurin activity. The results may be ascribed to the decreased free
      immunophilin in brain after infusion of corresponding immunosuppressant, or the
      fact that two immunophilin-immunosuppressant complexes have not completely
      identical interaction sites on calcineurin.

PMID- 16801219
TI  - Expression analysis of genes involved in fat assimilation in human monocytes.
AB  - The metabolic syndrome X is characterized by a group of risk factors such as
      obesity, atherogenic dyslipidemia, hypertension, and insulin resistance. To study
      the functional alterations resulting from genetic variations, ex vivo studies are
      one option to be carried out. Since it is not an easy procedure to obtain cells
      from the related tissues ex vivo, the aim of the present study was to investigate
      whether monocytes can serve as model cells. The purpose was to check if monocytes
      are insulin target cells or not and to elucidate the expression of genes involved
      in fat assimilation. Human monocytes were drawn from venous blood of healthy
      donors, aged 25 - 30, using density gradient separation and antibody-based
      magnetic cell sorting of CD14-positive cells. An expression analysis of genes was
      performed using RT-PCR and Western Blot. Transcripts of the three splice-variants
      of the Acyl-CoA binding protein (ACBP), the Medium-chain Acyl-CoA Synthetase 1
      (MACS1), the Insulin Receptor (INSR) and the Peroxisome Proliferator-activated
      Receptor gamma (PPARgamma) are consistently expressed in monocytes of all donors.
      Differences in gene expression between donors are found for two other members of
      the MACS-family, the fatty acid transport protein 3 (FATP3) and the FATP4. On
      protein level, we tested for ACBP expression. The ACBP protein is consistently
      expressed in monocytes of all donors. Human monocytes are insulin target cells
      and capable of fatty acid metabolism to some extent. Ex vivo-derived monocytes
      could be used in additional studies for analyzing differences in genotype
      dependent expression levels of genes involved in fat assimilation such as ACBP,
      MACS1 or PPARgamma.

PMID- 16801220
TI  - What is the biological significance of the two mitofusin proteins present in the
      outer mitochondrial membrane of mammalian cells?

PMID- 16801221
TI  - How I became a biochemist.

PMID- 16801222
TI  - The role of gender and sexual relations for young people in identity construction
      and youth suicide.
AB  - The suicide rate among young people in Australia has caused considerable concern
      and been the focus of research and intervention. Issues related to sexuality and
      gender can be the source of conflict for young people within their communities,
      and have been implicated in suicide attempts. This paper examines the cultural
      context of youth suicide, and asks how youth suicide may be related to emerging
      sexual identity, which all young people must negotiate through the customs,
      discourse and taboos of their society. In particular, it focuses on the situation
      of young heterosexual women. The findings are based on interviews with 41 young
      people, parents and youth service providers regarding youth suicide. Interviews
      were semi-structured and open-ended, and conducted in a suburban community. They
      included the use of scenarios or vignettes. Finding, suggest that traditional
      constructions of gender remain widespread, and that these are often
      disadvantageous to both young women and young men. Parents may be unaware that
      they have little control over, or even knowledge about, their teenagers'
      behaviour. Young people are more inclined to confide in their friends, who may
      not be equipped to deal with crises.

PMID- 16801223
TI  - Love, lifestyles and the risk of AIDS: the moral worlds of young people in Bobo
      Dioulasso, Burkina Faso.
AB  - The HIV epidemic has had a profound impact on people's everyday life in most
      African societies. A large proportion of all new HIV infections involves young
      people between 15 and 25 years. The objective of this paper is to explore local
      moral worlds of young people in Bobo-Dioulasso, Burkina Faso, and discuss how the
      HIVS epidemic affects their reflections on their everyday life and their
      perceptions of sexual relationships. Based on anthropological fieldwork,
      including focus-group discussions, in-depth interviews and participant
      observation, a total of 57 young people between 15 and 25 years were followed
      over a 3-month period. Using the notion of 'lifestyle', the paper shows how
      structural factors of unemployment and poverty paired with global discourse on
      AIDS present the young people with frustrations and quandaries in relation to
      their hopes and images of love, faithfulness and modern living. The data shows
      that the HIV epidemic contributes to and accelerates their feeling of living in a
      risk society and of being at risk. In order to cope with these uncertainties and
      contingencies, local discourses of trust and fidelity become extremely important
      and to most young people HIV prevention is synonymous with finding a faithful
      partner and/or using condoms.

PMID- 16801224
TI  - Filipino experience of ritual male circumcision: knowledge and insights for anti
      circumcision advocacy.
AB  - Male circumcision is a well-publicised phenomenon, but much of what is known at
      the international level concerns neonatal medical circumcision in some Western
      countries and ritual circumcision among young men entering into adulthood in
      certain countries in Africa. This paper aims to add to this understanding by
      focusing on Filipino men's experience of ritual circumcision. Data were derived
      from a 2002 Philippine circumcision study-a component in a Southeast Asian
      research study of genital enhancement practices with an advocacy purpose. As part
      of the study, interviews were conducted with 114 circumcised Filipino males, of
      varying ages, who were selected purposively. The report highlights the important
      links in this context between circumcision, masculinity and male identity. It
      points too the role of the broader community in sustaining such practices and the
      challenges that must be faced by anti-circumcision campaigners in making their
      efforts culturally appropriate.

PMID- 16801226
TI  - Barriers to and facilitators for female participation in an HIV prevention
      project in rural Ethiopia: findings from a qualitative evaluation.
AB  - Ethiopian women face complex social and cultural factors that influence their
      probability of HIV infection. HIV prevention efforts among this population are
      particularly important; however, female participation in a rural, HIV prevention
      project has been minimal. This programme evaluation investigated barriers and
      facilitators influencing women's ability to participate in project activities.
      Evaluation data were collected through nine focus groups and 20 semi-structured
      interviews, which were conducted between October and November 2003. The main
      themes found to negatively influence women's decisions to participate in this HIV
      prevention activity included: domestic workloads, lack of education and
      awareness, and cultural norms that have discouraged discussions about HIV and
      sexuality. Domestic chores, which are labour intensive and limit time and energy,
      were found to be the primary barrier to participation among women. Respondents
      also indicated that female illiteracy and limited educational attainment occur
      within a social context that traditionally supports education for men but
      discourages formal knowledge among women, including HIV prevention. Lack of
      education and inability to freely discuss sexuality denies women access to health
      information, potentially exposing women to adverse consequences such as HIV
      infection. Identified facilitators of participation included a radio serial drama
      and the one female peer educator associated with the project.

PMID- 16801225
TI  - Race, social support, and coping strategies among HIV-positive gay and bisexual
      men.
AB  - Few studies have examined the relation between race, social support, and coping,
      particularly among HIV-infected individuals. We examined the relation of race and
      social support to coping with HIV infection in a sample of 121 gay and bisexual
      men (64 African American, 57 White). Compared to White participants, African
      Americans reported higher use of multiple coping strategies. High levels of
      perceived social support were related to greater use of positive coping and
      seeking support; lower levels of social support were related to greater use of
      self-destructive coping. There were no race-related differences in social
      support, and no race by social support interactions. Possible explanations for
      observed cultural differences and coping challenges of African American gay and
      bisexual men with HIV are discussed.

PMID- 16801227
TI  - Who's right? Human rights, sexual rights and social change in Barbados.
AB  - Currently, in a number of public and semi-public forums in Barbados, the idea of
      'sexual rights' is being discussed and debated. However, different meanings are
      attached to 'rights'. This paper examines how these meanings demonstrate that
      different interpretations of sexuality, society, and morality are circulating
      through Barbados today. It also addresses whether or not sexual rights discourses
      are the best way to advocate for social justice or bring about changes to socio
      sexual attitudes in the Caribbean. It is argued that framing justice and equality
      through rights talk may have deleterious effects for its advocates, as there is
      no 'clear' or transparent universality as to what rights means. It is suggested
      that it may be more efficacious for groups who are stigmatized based on sexual
      orientation to develop vernacular strategies with values and/or logics stressing
      elements of justice, equality, dignity and respect for personhood, which include
      but also move beyond sexual orientation as a principal identification.

PMID- 16801229
TI  - Initial force and postural adaptations when pushing and pulling on floor surfaces
      with good and reduced resistance to slipping.
AB  - The objective of the present study was to determine whether differences in the
      frictional properties of a floor surface may affect the kinematics and kinetics
      of pushing and pulling. Eight male participants were required to push and pull a
      four-wheeled trolley over two level surfaces, on which were mounted floor
      coverings with good (safety floor) and reduced (standard floor) frictional
      properties. A psychophysical approach was used to determine the initial maximum
      acceptable horizontal force required to move the trolley over a short distance (3
      m). Three-dimensional (3D) hand and ground reaction forces and 3D postures were
      measured during initial force exertions. The results showed that psychophysically
      derived measures of initial horizontal force and horizontal components of hand
      forces did not differ significantly between floor surfaces. Despite the ability
      to exert similar forces, the measured maximum coefficient of friction varied
      according to floor surface. These changes reflected significant alterations in
      vertical and horizontal components of ground reaction and vertical hand forces,
      suggesting that participants had maximized the frictional properties available to
      them. Postures also changed as a consequence of floor surface, with significant
      changes occurring in knee flexion and trunk extension. This study has shown that
      handlers involved in the pushing and pulling of trolleys are capable of adjusting
      posture and the direction of hand and foot forces in order to compensate for
      reduced levels of floor friction. This has particular relevance when assessing
      the musculoskeletal loads imposed on the handler and the likely mechanisms of
      injury resulting from variations in floor conditions when workers undertake
      pushing and pulling tasks in the workplace.

PMID- 16801230
TI  - Effects of a thermal-insulating mouse pad on temperature of forearm and hand
      during computer tasks.
AB  - This laboratory experiment studied the effects of a thermal-insulating mouse pad
      on arm temperature and comfort during computer work. Fourteen subjects performed
      two 20-min computer tasks (a mouse task and a combined task alternating keyboard
      and mouse use), under three conditions, namely with: 1) a thermal-insulating pad;
      2) a placebo pad; 3) no pad (desktop). The temperatures of the forearm, wrist,
      hand and fingers were measured with four thermocouples. Comfort and discomfort
      were determined by two visual analogue scales. No arm temperature differences
      were found between the experimental conditions after performing the combination
      task in any location. After the mouse task, however, arm temperature decreased
      significantly less with the thermal-insulating mouse pad than with the placebo
      pad. The thermal-insulating pad was rated as more comfortable and less
      uncomfortable than a regular desktop during mouse tasks. A large size is
      recommended for the thermal-insulating pad.

PMID- 16801231
TI  - An evaluation of a lane support system for bus rapid transit on narrow shoulders
      and the relation to bus driver mental workload.
AB  - The use of dedicated bus shoulders is a key method for implementing bus rapid
      transit (BRT) in areas that do not have the space for additional infrastructure.
      However, the narrow width of the bus shoulder and the need to anticipate traffic
      hazards in the adjacent lane can both be significant stressors for bus drivers.
      Bus driver mental workload and stress in response to these conditions should be a
      significant concern both for operational safety and driver health. This pilot
      study evaluated the potential stressors of traffic density and shoulder width in
      the context of an express BRT service in a large US metropolitan area. In
      addition, the study considered the potential role of a prototype lane support
      system (LSS) to support vehicle control within the narrow shoulder boundaries.
      Ten experienced bus drivers drove an actual route with an instrumented bus
      equipped with and without LSS. Self-reported effort was recorded along with
      performance measures of speed and position control relevant to mobility and
      safety objectives. Bus drivers did note stressors in the BRT environment and the
      prototype LSS. However, the use of the shoulder during high-density traffic
      conditions did improve mobility. Moreover, the LSS did enhance safety on the
      shoulder when there was high-density traffic in the adjacent lane. However, there
      was no evidence that the LSS reduced bus driver workload while operating in the
      narrow shoulder. Future research should consider the impact of BRT operations and
      support systems on bus driver mental workload and stress, and support the
      deployment of such devices for bus operations on shoulders during high traffic
      volumes.

PMID- 16801232
TI  - The feasibility of repositioning ability as a tool for ergonomic evaluation:
      effects of chair back inclination and fatigue on head repositioning.
AB  - Poor posture has been suggested as one of the main factors contributing to the
      high prevalence of neck pain in video display unit (VDU) users, but no clear
      association between pain and any particular resting neck posture has been found.
      Postural awareness of the neck, as indicated by the repositioning accuracy, may
      therefore be an appropriate measure and potentially useful assessment tool. The
      objective of this study is to examine whether posture and fatigue affect the head
      repositioning ability in typical VDU usage. A group of 20 healthy participants
      reproduced a normal comfortable posture for forward, upright and backward chair
      back inclinations in random order both before and after fatigue of the upper
      trapezius muscles. Ten repetitions of the posture were recorded for 2 s each, and
      the angular and translational deviations from the original head position were
      measured with regard to the external environment (head in space repositioning)
      and with regard to the trunk (head on trunk repositioning). Analysis by repeated
      measures ANOVA showed significant effects and interactions of fatigue and chair
      back inclination on the repositioning errors in the sagittal plane, which
      typically showed systematic trends towards certain postures rather than random
      errors around a mean position. While further work is required to examine the
      ergonomic impact of impaired repositioning ability, head repositioning is
      sensitive to ergonomic factors such as seating configuration and fatigue, and may
      therefore be a useful tool for evaluation of static working postures.

PMID- 16801233
TI  - Linear temporal characteristics of heart interbeat interval as an index of the
      pilot's perceived risk.
AB  - The concept of adaptive automation is the first commendable step towards machine
      monitoring and support of the human operator behaviour and performance. Despite a
      large number of studies, the concept is still not sufficiently mature and more
      experimental studies are required to enable its application in the real world. As
      a small contribution in this direction, this experimental study made an effort to
      develop some techniques for online assessment of the pilot's perceived risk of
      the consequences resulting from their inability to execute a task adequately.
      Linear dynamical characteristics of 60 pilot's heart interbeat intervals were
      used for the assessment. Past research has shown that such 'perceived risk'
      influences the pilot's need for an automation aid. The preliminary results of
      this study suggested that the frequency and power of the heart interbeat interval
      dominant cycle, together with the characteristics of the energy contained in the
      power spectrum, can be sensitive indices of the level of perceived risk. The
      study techniques and preliminary results appear promising for incorporation into
      the algorithm of an intelligent online monitoring and alerting system on future
      aerospace vehicles to define the moments when the human supervisory controllers
      require an automation aid.

PMID- 16801234
TI  - Changes in gait kinematics and posture with the use of a front pack.
AB  - The objective of this study was to determine if posture during gait can be
      affected by position of the load. It was hypothesized that the front pack would
      result in postural changes in the gait cycle, compared to a similarly loaded
      backpack. Thirteen healthy adults, free of any injury, volunteered to participate
      in this study. Two dimensional video data were collected at 50 Hz using a
      MacReflex video system. A backpack and a front pack were compared using loads of
      10 and 15% of body weight. Markers were placed on the ear, acromion, greater
      trochanter and lateral joint line of the knee, lateral malleolus and fifth
      metatarsophalangeal joint. Data were collected while the participants walked at
      0.75 stride/s. The data were used to calculate joint angles and displacements
      during each gait cycle. There was a significant difference noted in angles of the
      hip flexion, with the backpack condition demonstrating a greater flexion in each
      stride than either the control or front pack. Both backpack and front pack
      conditions demonstrated a significant change in neck motion compared to the
      control condition. The results of the position analysis over time also revealed
      an increase in the forward head position when participants were wearing the
      backpack compared to either the control or the front pack condition. It was
      concluded that the use of a front pack results in a more upright posture in gait,
      when compared to a backpack carrying the same load.

PMID- 16801235
TI  - Pushing and pulling: personal mechanics influence spine loads.
AB  - This study assessed several mechanical issues related to low back loading during
      pushing and/or pulling tasks. Nine male participants performed two-handed pushing
      and pulling tasks at two handle heights with three loads, using a cable pulley
      system. Four of these men were professional firefighters trained in performing
      pushing and pulling tasks while the other five were graduate students who lacked
      manual work experience. The more experienced firefighters produced less spinal
      compression and shearing forces when compared to the less experienced students
      under the same conditions. The firefighters were able to create less muscle
      activation as compared to the students, which indicated a more efficient
      technique. The main contributing factors to the forces produced on the low back
      were the quantity of the load being pushed or pulled, handle height, experience
      level and the technique of the participant. Thus, attempts to set load limits for
      pushing and pulling tasks are difficult, since technique has such a large
      influence on back loading. In order to create safer working environments,
      education on proper pushing and pulling techniques is very important--more
      important than the physical variables in many cases.

PMID- 16801237
TI  - Review and current status of emulsion/dispersion technology using an internal
      gelation process for the design of alginate particles.
AB  - Emulsification/internal gelation has been suggested as an alternative to
      extrusion/external gelation in the encapsulation of several compounds including
      sensitive biologicals such as protein drugs. Protein-loaded microparticles offer
      an inert environment within the matrix and encapsulation is conducted at room
      temperature in a media free of organic solvents. Recently, the concept of
      internal gelation has been applied to formulating nanoparticles as drug delivery
      systems. Emulsification/internal gelation technologies available for
      microparticles preparation, particularly that involving alginate polymer, are
      described as well as recent advances towards applications in nanotechnology.
      Those methods show great promise as a tool for the development of encapsulation
      processes, especially for the new field of nanotechnology using natural polymers.

PMID- 16801238
TI  - Emulsification preparation of chitosan-urethane microbeads in the presence of a
      water-soluble blocked diisocyanate, containing furanone homosyrine lactone
      bacterial inhibitors.
AB  - Chitosan is an abundant naturally occurring biopolymer that is biocompatible, of
      low toxicity and is well suited as a carrier for a range of active agents.
      Restrictions imposed by this biopolymers unique solubility requirements make if
      difficult to process. One approach to an internal setting system is to employ the
      water-soluble blocked isocyanate hexamethylene-1,6-di(aminocarboxysulphonate)
      (HDACS) in order to cross-link the chitosan and form microspheres in situ
      utilizing simple emulsion systems. Chitothane microspheres are capable of
      delivering active agents at controlled release rates and offers a viable
      alternative to external set methodologies utilizing aldehydes or similar cross
      linking agents.

PMID- 16801239
TI  - Micronization and microencapsulation of felodipine by supercritical carbon
      dioxide.
AB  - Felodipine (FLD) is a poorly water-soluble drug. To improve its dissolution rate,
      the rapid expansion of supercritical solutions (RESS) technique was used to
      prepare micronized FLD drug particles, which were encapsulated in poly-(ethylene
      glycol) 4000 (PEG 4000). The physical properties of the encapsulated drug
      particles were characterized by a variety of analytical methods, including
      optical light microscopy, scanning electron microscopy (SEM), differential
      scanning calorimetry (DSC) and powder X-ray diffraction (powder-XRD) and the
      dissolution behaviour of FLD was studied in the microparticles. The supercritical
      condition of micronized FLD occurred at a relatively high pressure and moderate
      temperature. FLD-PEG 4000 microparticles compared well with micronized FLD. RESS
      was effective in reducing the particle size of FLD; spot-shaped micronized FLD
      and popcorn-shaped FLD-PEG 4000 microparticles were observed. The particulate
      properties of the microparticles included a narrow distribution and uniform size.
      Thermodynamic analysis showed an implantation interaction between FLD and PEG
      4000 molecules, but no polymorphism in the micronized FLD or FLD-PEG 4000
      microparticles. FLD-PEG 4000 microparticles had a significantly faster drug
      dissolution rate than micronized FLD. These data show that RESS can be used to
      prepare FLD-PEG 4000 microparticles with small particle size (2-6 microm) and
      enhanced dissolution rate.

PMID- 16801240
TI  - Wound dressings containing bFGF-impregnated microspheres.
AB  - The primary objective was to synthesize a novel wound dressing containing basic
      fibroblast growth factor (bFGF)-loaded microspheres for promoting healing and
      tissue regeneration. Gelatin sponge was chosen as the underlying layer and
      elastomeric polyurethane membranes were used as the external layer. To achieve
      prolonged release, bFGF addition was loaded in microspheres. The microspheres
      were characterized for particle size, in vitro protein release and bioactivity.
      The bilayer dressings were tested in in vivo experiments on full-thickness skin
      defects created on pigs. Average size of the microspheres was 14.36 +/- 3.56
      microm and the network sponges were characterized with an average pore size of 80
      160 microm. Both the in vitro release efficiency and the protein bioactivity
      revealed that bFGF was released in a controlled manner and it was biologically
      active as assessed by its ability to induce the proliferation of fibroblasts. It
      was observed that sustained release of bFGF provided a higher degree of reduction
      in the wound areas. Histological investigations showed that the dressings were
      biocompatible and did not cause any mononuclear cell infiltration or foreign body
      reaction. The structure of the newly formed dermis was almost the same as that of
      the normal skin. The application of these novel bilayer wound dressings provided
      an optimum healing milieu for the proliferating cells and regenerating tissues in
      pig's skin defect models.

PMID- 16801241
TI  - Preparation of stable alginate microcapsules coated with chitosan or
      polyethyleneimine for extraction of heavy metal ions.
AB  - Stable alginate microcapsules in dried form containing bis(2,4,4-trimethylpentyl)
      monothiophosphinic acid (HA) were prepared by coating of fresh alginate
      microcapsules with chitosan or polyethyleneimine (PEI). The thickness of coatings
      was estimated by electron probe microanalysis (EPMA), along with electron
      microscopy (SEM), as well as comparison of uptake percentage of coated and
      uncoated hollow capsules. Characterization of microcapsules was carried out by
      Ag(+) uptake experiments, destructive chemical analyses and thermogravimetric
      methods (TG and DTA). Chemical stability tests in HNO(3) and NaNO(3) media
      indicated that the coating with 4-double layer chitosan or mono-layer PEI led to
      an appreciable enhancement of impermeability in the range of pH > 1 or [Na(+)] <
      1 M (mol dm(-3)). Unfortunately, multiple coating causes some extractant losses
      due to effect of physical stress during the coating; however, PEI-coated
      microcapsules nearly completely hold their extractant content. Stable extractive
      microcapsules have an appreciable potential for the selective removal of heavy
      metal ions.

PMID- 16801242
TI  - Zein microspheres as drug/antigen carriers: a study of their degradation and
      erosion, in the presence and absence of enzymes.
AB  - In the laboratory, zein microspheres are being investigated as drug/vaccine
      delivery systems. Preliminary experiments revealed that the release of an
      entrapped solute (ovalbumin, a model antigen) was limited when particles were
      incubated in phosphate buffered saline over a number of days. To understand the
      slow and limited release of the guest molecule and predict microsphere fate in
      vivo, the degradation of zein microspheres in different media, in the presence
      and in the absence of enzymes, was investigated in vitro. Zein microspheres were
      incubated in five different media: chloride Buffer (pH 2), Acetate Buffer (pH 5),
      Phosphate Buffered Saline (pH 7.4), gastric simulated fluid and gastro-intestinal
      simulated fluid for 1 week. Changes in suspension turbidity and pH, microsphere
      morphology and zein composition in the release medium was followed with time. The
      results showed that zein microspheres were extremely resistant to degradation in
      the absence of enzymes (which explains the slow release of entrapped solute), but
      were degraded by pepsin and pancreatin enzymes in simulated gastric and
      intestinal fluids, respectively (which indicates that release is likely to be
      much faster following oral microsphere administration). However, when
      administered via routes where enzymes are not present, e.g. intra-muscular,
      release is likely to be slow.

PMID- 16801244
TI  - Colon-specific delivery of mesalazine chitosan microspheres.
AB  - Mesalazine (5-ASA) is a cyclo-oxygenase inhibitor and anti-inflammatory drug
      effective in Crohn's disease and ulcerative-colitis. As 5-ASA is rapidly absorbed
      from the small intestine and it is necessary to develop a colon-specific delivery
      system for it. Coated chitosan microspheres were used for this purpose by an
      emulsion-solvent evaporation technique based on a multiple w/o/w emulsion. Four
      hundred milligrams of chitosan solution (3%) in dilute acetic acid (0.5 M)
      containing 12% 5-ASA was dispersed into 2 ml solution of cellulose acetate
      butyrate (CAB) in methylene chloride. The primary induced w/o emulsion was
      dispersed into a 1% PVA aqueous solution to produce a w/o/w multiple emulsion and
      was stirred for approximately 2.5 h. The produced microspheres were separated,
      washed and dried. Release of 5-ASA from microspheres was studied in different pHs
      1.2, 7.4, 6.8 and 6.8 in the presence of caecal contents of rat. The average size
      of microspheres was 200 microm. The highest yield efficiency (80%) was seen in
      medium molecular weight (MW) chitosan with a 1 : 2 core/coat ratio and the
      greatest loading efficiency (85%) related to the microspheres of the same type of
      chitosan but with a 1 : 1 core/coat ratio. Decreasing the coat content and
      increasing chitosan Mw increased the bioadhesion significantly (p < 0.05).
      Microspheres of chitosan with medium Mw and 1 : 1 core/coat that showed the
      greatest release of drug (near 80%) in the presence of caecal secretions with a
      zero-order mechanism, near zero per cent in pH 1.2 after 2 h, max 20% in pH 7.4
      after 3 h and near 60% in pH 6.8 after 8 h seem suitable for site-specific
      delivery of 5-ASA in vitro.

PMID- 16801243
TI  - DEET-loaded solid lipid particles for skin delivery: in vitro release and skin
      permeation characteristics in different vehicles.
AB  - DEET (N,N-diethyl m-toluamide) is a lipophilic compound which has a common use as
      an insect repellent and causes not only skin irritation but also systemic side
      effects at high concentrations in long-term skin application. In this study, DEET
      is incorporated into solid lipid particles, a colloidal drug delivery system, in
      order to reduce the percutaneous permeation and avoid toxic effects and also
      maintain drug effectiveness on the skin surface for a long duration of insect
      repellence. Solid lipid particles were prepared based on emulsion systems at
      different concentrations and after the characterization studies, the formulation
      with 20% lipid phase and 1:1 drug:lipid ratio was carried to in vitro release and
      skin permeation studies. Solid lipid particles with DEET were compared to free
      DEET using cream and hydrophilic gel vehicles. Results showed that incorporation
      of DEET into solid lipid particles reduced the release rate and skin permeation
      of DEET. Imaging studies using scanning electron microscopy showed that there
      were still solid lipid particles on skin surface after 2 h indicating that DEET
      could be present for a longer time on the application site.

PMID- 16801245
TI  - Lipid microencapsulation in starch.
AB  - Short microwave heating of granular potato, waxy corn and tapioca starches with
      such lipids as cis-9-octadecenoic acid (oleic acid), cis,cis-9,12-octadecadienoic
      acid (linoleic acid), octadecanoic acid (stearic acid), ethyl cis-9
      octadecenoate, ethyl cis,cis-9,12-octadecadienoate and methyl octadecanoate
      provided microcapsules in which encapsulated guest molecules did not interact
      with starch microcapsules. On the formation of microcapsules, the lipid guest
      molecules did not react to starches. The encapsulation yield varied between
      almost 11-94%.

PMID- 16801246
TI  - Patent briefing.

PMID- 16801247
TI  - Literature alerts.

PMID- 16801249
TI  - School-based peer support groups: a new approach to the prevention of disordered
      eating.
AB  - The goal of the present study was to evaluate the effectiveness of a school-based
      peer support group designed to improve body esteem and global self-esteem and to
      reduce negative eating attitudes and behaviors. A total of 214 girls in grades 7
      and 8, 115 of whom were in the control group, completed self-report
      questionnaires immediately before and following the intervention, and three
      months later. The findings revealed that participation in the 10-session group,
      facilitated by public health nurses, led to increases in weight-related esteem
      and decreases in dieting. The role of peer support groups in the prevention of
      disordered eating is discussed.

PMID- 16801250
TI  - Replication of a peer support program designed to prevent disordered eating: is a
      life skills approach sufficient for all middle school students?
AB  - The evaluation of a school-based peer support group previously shown to improve
      body esteem and global self-esteem and reduce dieting in young adolescent girls
      was replicated in the present study. A total of 282 girls in grades 7 and 8, 196
      of whom were in the control group, completed self-report questionnaires
      immediately before and after the life skills intervention, and 3 months later.
      Contrary to the findings reported in the original study, participation in the 10
      session peer support group did not lead to improvements in body esteem or eating
      attitudes and behaviors beyond what was experienced by the control group.
      Interestingly, participants of the current intervention group exhibited higher
      disordered eating scores at baseline than those participants in the original
      study. Implications for matching prevention curriculum with the developmental and
      symptom levels of students are discussed.

PMID- 16801251
TI  - A health service perspective on anorexia nervosa.
AB  - This article reviews anorexia nervosa from a health services perspective. From
      such a perspective, costs of care, changes in insurance types, lack of
      empirically supported treatments, and involvement of legislative and judicial
      processes are discussed. Based on this review, processes for designing optimal
      insurance strategies are outlined, needs for treatment, service, and prevention
      development suggested, and the need for systematic evaluation of effective
      treatments identified.

PMID- 16801252
TI  - Nutrition and eating in female college athletes: a survey of coaches.
AB  - The purpose of the present study was to gather information from coaches regarding
      their monitoring/management of athlete eating and weight, knowledge of
      nutritional health issues, availability of prevention/intervention services for
      athletes at their school, experience with athletes exhibiting symptoms of eating
      and body image disturbances, and their attitudes toward eating and weight in the
      sport. A total of 303 coaches (51% response rate) involved in six sports (i.e.,
      gymnastics, swimming, basketball, softball, track, and volleyball) at all levels
      of collegiate competition (NCAA Divisions I, II, III, and NAIA) completed a 40
      item survey. Gender was found to be related to differential responding on only
      one of the 40 items, while sport and level of competition were related to
      responses on multiple items. Gymnastics coaches and NCAA Division I coaches
      differed significantly from coaches of other sports and divisions in that they
      reported more monitoring/management behaviors, had more experience with athletes
      exhibiting eating disturbances, and had more resources available for preventing
      and treating athletes with eating disorders. Gymnastics coaches also differed
      from other coaches on a number of items related to their attitudes toward eating
      and weight in the sport. Many coaches have encountered disturbed eating among
      their athletes, and some of their coaching attitudes and behaviors may
      inadvertently increase the risk for such disturbances. Implications for clinical
      and sport psychologists providing prevention or intervention services to
      intercollegiate athletes are discussed.

PMID- 16801254
TI  - Healing through connection: self-disclosure in psychotherapy.

PMID- 16801253
TI  - Drive for thinness and fear of fat: separate yet related constructs?
AB  - The terms drive for thinness and fear of fat are consistently used in the
      literature to describe eating disorders in their clinical and sub-clinical forms,
      yet distinct definitions of each are not provided. Although similar on first
      examination, these terms may represent two distinct constructs in the
      motivational factors of persons at risk for developing eating disorders. The
      following article presents the notion that drive for thinness and fear of fat are
      separate yet related constructs, perhaps representing approach and avoidance
      mechanisms in persons at risk. The implications for counseling and practice and
      directions for further research are provided.

PMID- 16801255
TI  - Evaluating treatment outcomes: a pragmatic approach.

PMID- 16801257
TI  - Stories I tell my patients. Radio station FATT.

PMID- 16801258
TI  - Characterization of the skin penetration of a hydrocarbon-based weapons
      maintenance oil.
AB  - Break-Free CLP is a commercial petroleum-based liquid used for cleaning,
      lubricating, and protecting firearms that is used in the United States by
      military personnel, police, and individual gun owners for maintaining a wide
      variety of firearms. According to its material safety data sheet (MSDS), Break
      Free CLP is predominately polyalphaolefin oil but also contains dibasic ester and
      isoparaffinic hydrocarbons; all of these ingredients are known to induce skin
      irritation in laboratory animals. Studies completed in our labs found that
      repeated topical application of Break-Free CLP to the backs of CD-1 mice produced
      evidence of systemic effects. Studies were conducted to characterize the dermal
      penetration of Break-Free CLP in mouse, rat, and pig skin to provide insight on
      possible factors or causes of skin irritation and systemic effects observed in
      previous studies. Mouse skin was 37 times more permeable to Break-Free CLP than
      pig skin and 6 times more permeable than rat skin. Flux measurements from static
      diffusion cells showed an inverse correlation with mouse, rat, and pig skin
      thickness. The concentration of Break-Free CLP in mouse skin was 4.5 times higher
      than the amount found in rat skin and about 17 times higher than the amount
      absorbed by pig skin. These results support the idea that Break-Free CLP causes
      skin irritation and systemic effects in the mouse by both penetrating through and
      accumulating in the skin. The findings for rat and pig skin are probably most
      representative of Break-Free CLP flux into and through unprotected human skin and
      suggest that dermal toxicity studies in CD-1 mice overestimate the risk to
      humans. These results, nevertheless, suggest that persons handling or using Break
      Free CLP should protect the skin from possible exposure.

PMID- 16801263
TI  - History of trauma field triage development and the American College of Surgeons
      criteria.
AB  - The use of trauma field triage criteria is designed to match a patient's injury
      type and severity to prioritized transport and an institution with the resources
      to provide timely, definitive care. Triage schemes used in austere environments
      created by war or mass casualty events are less applicable to day-to-day civilian
      trauma. Civilian triage criteria, developed and refined over the past 25 years,
      rely on physiologic, anatomic, and mechanistic indicators of severe injury in an
      attempt to optimize overtriage and undertriage. As organized trauma systems
      continue to mature, the need for more accurate direction of high- versus low
      acuity patients to regional centers, stratified by their capabilities, becomes
      more apparent and is essential in avoiding a completely 'exclusive' trauma
      system. New technology utilizing vehicular telemetry and Web-based information
      systems may simplify the seemingly simple but often formidable task of creating
      destination decision rules for victims of major injury.

PMID- 16801264
TI  - Trauma triage: New York experience.
AB  - New York State developed a statewide trauma program in the early 1990s.
      Designation of trauma centers and prehospital triage of patients by emergency
      medical services are pillars of the system. Outcomes are evaluated as part of the
      quality improvement system. New York has a statewide trauma registry with
      population-based data for all of the state but New York City. Studies made
      possible because of the trauma registry provided evidence to guide revision of
      the emergency medical services trauma triage protocol for adult patients. For
      example, pulse < 50 or > 120 beats/min was retained as a physiologic criteria,
      while crumple zone and crash speed were eliminated as mechanism criteria.
      Patients with certain physiologic criteria treated in regional centers showed a
      considerably reduced mortality rate when compared with patients treated in area
      trauma centers and noncenters. Other "high-risk" populations were identified for
      special consideration by emergency medical technicians for trauma center
      transport because of their associated higher mortality. One "high-risk" group,
      patients older than 55 years or younger than 5 years, has associated 11%
      mortality (compare with a statewide average of 7.43%) and represents 41% of all
      registry patients. Population-based trauma registries and structured prehospital
      trauma records that accurately record the presence or absence of trauma criteria
      are essential to evaluate trauma triage criteria; improve quality, efficiency,
      and access; and guide care.

PMID- 16801265
TI  - Studies evaluating current field triage: 1966-2005.
AB  - The American College of Surgeons (ACS) field triage guidelines are used to
      determine which patients require prompt transport to a trauma center and which
      can be transported to a lower-level facility. The objective of this report was to
      conduct a literature review to determine the sensitivity and specificity of the
      ACS field triage criteria and each step of the criteria. The bibliographic
      database MEDLINE was used to conduct a literature search for relevant English
      language articles published between 1966 and 2005. The search was conducted by
      combining the Medical Subject Headings (MeSH) "emergency medical services,"
      "triage," and "wounds and injury." To ensure that the search was comprehensive,
      the reference sections of all selected articles were searched for additional
      relevant references and searches by other organizations were reviewed to identify
      additional relevant articles. The MEDLINE search identified 542 titles. The
      author reviewed the titles, and 107 abstracts were selected for further review.
      Through the MEDLINE search, the reference section review, and the review of other
      searches, 80 articles were identified as relevant. Of those, five studies
      evaluated the full ACS criteria. Two of these calculated the specificity (8%)
      and/or sensitivity (95%-97%) of the ACS criteria. The remaining studies looked at
      the percentage of patients transported or admitted to a trauma center. Three
      studies looked at the predictive value of the physiologic step, and one of these
      calculated the sensitivity (56%) and specificity (86%). Two studies specifically
      analyzed the anatomic step. One of these calculated the sensitivity (45%). This
      search found that there is insufficient evidence to support the overall ACS field
      triage criteria. However, of the various steps, the physiologic and anatomic
      steps had the best evidence to support them.

PMID- 16801266
TI  - Trauma triage: concepts in prehospital trauma care.
AB  - This report examines the efficacy of current trauma triage rules to determine the
      exigency of field care and transport of severely injured patients from a variety
      of medical populations.

PMID- 16801267
TI  - Prehospital triage of trauma patients: a trauma surgeon's perspective.
AB  - A number of triage tools have been developed and used to make triage decisions.
      Studies have demonstrated better outcomes in patients who receive care in trauma
      centers. The field triage decision scheme from the American College of Surgeons
      Committee on Trauma involves patient triage based on the presence of physiologic
      derangement, specific anatomic injuries, mechanism of injury, and comorbid
      factors. Issues such as distance to a trauma center (rural areas) and methods of
      transport (e.g., air, ground) complicate the prehospital triage of trauma
      patients. The best system for a given community or region is one that begins with
      a triage scheme that is evidence based to the greatest extent possible but is
      then modified based on community or regional resources and geography. Delivering
      the severely injured trauma patient to a facility that can provide optimal care,
      in the shortest amount of the time, remains the overarching principle.

PMID- 16801268
TI  - National Emergency Medical Services Information System (NEMSIS).
AB  - The absence of emergency medical services (EMS) patient care data has hindered
      development and evaluation of EMS systems. The National Highway Traffic Safety
      Administration (NHTSA), in cooperation with the Health Resources and Services
      Administration (HRSA), has provided funding to the National Association of State
      EMS Directors to develop a National EMS Information System (NEMSIS). NEMSIS is
      being designed to provide a uniform national EMS dataset, with standard terms,
      definitions, and values, as well as a national EMS database, with aggregated data
      from all states on a limited number of data elements. Forty-eight of the states,
      the District of Columbia, and three territories signed a memorandum of agreement
      documenting support for the NEMSIS project and expressing a desire for full
      implementation of the NEMSIS dataset. NHTSA has agreed to house the National EMS
      Database at its National Center for Statistics and Analysis. NHTSA, in
      cooperation with HRSA and the Centers for Disease Control and Prevention,
      recently entered into a cooperative agreement with the University of Utah School
      of Medicine to operate a NEMSIS Technical Assistance Center that will provide
      related assistance to official EMS agencies and to commercial software vendors.
      The Technical Assistance Center will also biannually assess state and territorial
      capabilities to provide data to the national EMS database. NEMSIS will provide a
      uniform national EMS dataset, with standard terms, definitions, and values, as
      well as a national EMS database, with aggregated data from all states on a
      limited number of data elements. Many of the potential benefits of implementation
      of NEMSIS are enumerated in this report.

PMID- 16801270
TI  - Telematics.
AB  - This report provides an overview of the public safety-related capabilities of fee
      based, in-vehicle wireless communications.

PMID- 16801269
TI  - Innovation possibilities for prehospital providers.
AB  - The national interest in disaster management and a burgeoning technology field
      are leading to the development of new approaches to emergency evaluation, triage,
      and treatment in prehospital and all hospital arenas. The ability to bring "hands
      on" expertise, both physically and technologically, as quickly as possible to the
      trauma patient brings the potential for real advancement in the field. This
      descriptive report presents several such concepts that are moving into reality.

PMID- 16801271
TI  - Field triage in disasters.
AB  - In man-made and natural disasters, prehospital providers and their emergency
      medical services systems may find it necessary to shift their triage methodology
      from a daily operational framework of treating the most severely injured patient
      first and providing the highest level of care for each patient to the concept of
      providing the greatest good for the greatest number of casualties. In a scenario
      where there are an overwhelming number of casualties, this shift will be
      necessary, both to identify critically injured patients who can benefit from
      immediate, life-saving interventions and to preserve prehospital and hospital
      resources. This report examines triage issues as they apply to mass casualty
      events.

PMID- 16801272
TI  - Air medical transport of trauma patients.
AB  - This report reviews the current status of air medical transportation of trauma
      patients. Aspects reviewed include patient care, dispatch, safety, and possible
      future directions in air medical patient care.

PMID- 16801273
TI  - Development of trauma care systems.
AB  - The modern-day history of trauma care system development encompasses a 45-year
      period. This report provides a timeline that highlights significant
      organizational and legislative initiatives that established the foundation of the
      current trauma system in the United States. The rationale for moving toward a
      public health approach in addressing trauma system development is explored and
      supported. Finally, the present-day issues confronting continued trauma system
      evolution and future opportunities are presented.

PMID- 16801275
TI  - HIPAA privacy and security implications for field triage.
AB  - The Health Insurance Portability and Accountability Act (HIPAA) of 1996 addresses
      insurance reforms, medical savings accounts, fraud and abuse provisions, and
      health information standards. This report discusses HIPAA issues that could
      impact field triage and emergency medical services.

PMID- 16801274
TI  - Emergency Medical Treatment and Active Labor Act and trauma triage.
AB  - The Emergency Medical Treatment and Active Labor Act (EMTALA) was conceived as a
      means to ensure that patients with emergent conditions would receive stabilizing
      care and to avert the potentially dangerous, economically driven, interhospital
      transfer of patients. This legislation and its subsequent application arrived
      near the time that regional and statewide trauma systems were established. Trauma
      systems were developed to guide optimal resource use for the injured patient
      regardless of the patient's ability to pay. Unfortunately, when coupled with
      current economic and litigation threats to community emergency and surgical
      practitioners, EMTALA represents a threat to the continuation of the trauma
      system concept. Trauma systems are dependent on a tiered hospital network where
      severely injured patients are taken to a hospital with resources aligned to
      manage the worst of injuries. When primary triage from the field cannot
      accomplish this task, secondary triage from a nondesignated or lower-level
      hospital to the higher-level trauma center is needed. EMTALA has served as a
      driver to change the priority for secondary triage from addressing the needs of
      the severely injured patient to filling community hospital surgical specialist
      emergency department on-call coverage gaps for less severely injured patients.
      Further, legal action associated with claims of EMTALA violations has needlessly
      extended medical examination and "stabilization" efforts at community emergency
      departments prior to needed secondary triage. Higher-level trauma centers will
      benefit from codifying system-wide emergency medical services practices related
      to primary and secondary triage, establishing trauma center capacity and divert
      practices, and initiating "transfer center" operations that control transfer of
      patients to these centers.

PMID- 16801276
TI  - Specialty coverage at non-tertiary care centers.
AB  - The fundamental tenet of a trauma system is to get the right patient to the right
      hospital at the right time. Although most injuries are minor or moderate and can
      be managed at local community hospitals, a significant minority of injured
      patients require extensive and expensive care to survive or minimize injury. Most
      prehospital trauma triage criteria address a combination of factors to consider,
      but this approach sometimes fails to identify patients with severe injuries and
      often burdens trauma centers with patients suffering minor injuries. It is
      critical to utilize a method to differentiate those injury victims who need the
      specialized expertise and resources available in trauma centers from those who
      can be adequately cared for locally. Although trauma centers assume the
      leadership role, in a truly inclusive system, all health care providers
      (prehospital, community hospitals, and trauma centers) have a defined role in
      providing care to patients with trauma. All these institutions should establish
      and maintain transfer agreements for the transfer of patients meeting system
      trauma triage criteria. Because prehospital triage criteria are not 100%
      sensitive, there should be a mechanism in place for the secondary triage of
      patients. Initial management of patients should continue while efforts are made
      to transfer the patient.

PMID- 16801277
TI  - Field triage, and the fragile supply of "optimal resources" for the care of the
      injured patient.
AB  - Conventional field triage schemes, including those discussed in this series of
      reports, assume a high degree of consistency in the availability of resources at
      designated receiving hospitals. In an organized trauma system, designated trauma
      receiving facilities of all levels are typically required to maintain a high
      level of consistency in terms of available facility and human resources for the
      care of the injured patient. These resources, both facility and provider, are
      becoming increasingly vulnerable to gaps in availability, however, for a variety
      of reasons. When gaps in resource availability do occur, their often
      unpredictable nature nullifies the effectiveness of any established triage
      protocol, may result in trauma center closures or downgrades, and undermines the
      entire system of care. It may be necessary in some regions to develop more
      flexible triage processes, creating a time-sensitive responsiveness to
      fluctuations in resource availability in a way that dynamically minimizes
      overtriage and undertriage.

PMID- 16801278
TI  - The effect of ambulance diversions on the development of trauma systems.
AB  - This report examines the complex relationship between the diversion of ambulances
      within an emergency medical services system and the management of trauma
      patients.

PMID- 16801279
TI  - Deliberations and recommendations.

PMID- 16801280
TI  - Predictors of intubation success and therapeutic value of paramedic airway
      management in a large, urban EMS system.
AB  - BACKGROUND: Endotracheal intubation (ETI) is commonly used by paramedics for
      definitive airway management. The predictors of success and therapeutic value
      with regard to oxygenation are not well studied. OBJECTIVES: 1) To explore the
      relationship between intubation success and perfusion status, Glasgow Coma Scale
      (GCS) score, and end-tidal carbon dioxide (EtCO2); 2) to describe the incidence
      of unrecognized esophageal intubations with use of continuous capnometry; and 3)
      to document the incremental benefit of invasive versus noninvasive airway
      management techniques in correcting hypoxemia. METHODS: This was a prospective,
      observational study conducted in a large urban emergency medical services system.
      Paramedics completed a telephone debriefing interview with quality assurance
      personnel following delivery of all patients in whom invasive airway management
      had been attempted. Continuous capnometry was used for confirmation of tube
      position in all patients. Descriptive statistics were used to document airway
      management performance, including first-attempt ETI success, overall ETI success,
      and Combitube insertion (CTI) success. In addition, the incidence of unrecognized
      esophageal intubation was recorded. The relationship between intubation success
      and perfusion status, GCS score, and initial EtCO2 value was explored using
      logistic regression. Finally, recorded SpO2 values and the incidence of hypoxemia
      (SpO2 < 90%) at baseline, following noninvasive airway maneuvers, and after
      invasive airway management were compared for perfusing patients. RESULTS: A total
      of 703 patients were enrolled over 12 months. First-attempt ETI success was 61%,
      and overall ETI success was 81%; invasive airway management (ETI or CTI) was
      unsuccessful in 11% of patients. A single unrecognized esophageal intubation was
      observed (0.1%). A clear relationship between airway management success and
      perfusion status, GCS score, and initial EtCO2 value was observed. Only EtCO2
      demonstrated an independent association with ETI success after adjusting for the
      other variables. Significant improvements in mean SpO2 and the incidence of
      hypoxemia over baseline were observed with both noninvasive and invasive airway
      management techniques in 168 perfusing patients. CONCLUSIONS: A relationship
      between intubation success and perfusion status, GCS score, and initial EtCO2
      value was observed. Capnometry was effective in eliminating unrecognized
      esophageal intubations. Both noninvasive and invasive airway management
      strategies were effective in increasing SpO2 values and decreasing the incidence
      of hypoxemia, with additional benefit observed with invasive airway maneuvers in
      some patients.

PMID- 16801282
TI  - Predictors of stroke during 9-1-1 calls: opportunities for improving EMS
      response.
AB  - OBJECTIVE: Only 31%-52% of stroke calls are accurately identified by 9-1-1
      dispatchers according to prior studies. Recognizing the time-dependent nature of
      acute stroke, better identification of stroke patients at the time of their 9-1-1
      calls may allow an improved prehospital response. We sought to identify any
      words/phrases that 9-1-1 dispatchers could use to identify more stroke calls.
      METHODS: Potential stroke calls were identified from emergency medical services
      run sheets, and the discharge diagnosis for each of these patients was obtained.
      The emergency medical services tapes were independently reviewed by two listeners
      who were blinded to the final diagnosis. Words/phrases previously associated with
      9-1-1 stroke calls mentioned by the caller were recorded. Other pertinent
      words/phrases were also recorded. Using the final diagnosis of stroke as the gold
      standard, the sensitivity, specificity, and positive likelihood ratio of each
      word and phrase were calculated. Cohen's kappa was calculated to assess
      interrater agreement. Data were collected for runs from October 2003 to July
      2004. RESULTS: A total of 176 tapes were reviewed (40 strokes, 136 nonstrokes).
      The presence of at least one of four criteria predicted 80% of all stroke calls:
      the word "stroke," facial droop, weakness/fall, and impaired communication. All
      criterion elements had very good interrater agreement (kappa > 0.7). The word
      "stroke" was highly predictive of actual stroke (positive likelihood ratio,
      2.27). CONCLUSIONS: The majority of stroke patients in this study could be
      identified by 9-1-1 dispatchers if the caller reported any one of the following
      four complaints: stroke, facial droop, weakness/fall, or impaired communication.

PMID- 16801281
TI  - What happens to SpO2 during air medical crew intubations?
AB  - OBJECTIVES: Studies finding adverse outcomes associated with emergency medical
      services intubation (ETI) have prompted recommendations for prehospital services
      to improve tracking of oxygenation during airway management. Our goals were to 1)
      implement a documentation requirement for helicopter EMS (HEMS) crews, entailing
      tracking and notation of the lowest SpO2 value (peri-ETI SpO2 nadir) occurring
      during HEMS crew ETI, and 2) assess the findings associated with the peri-ETI
      SpO2 documentation parameter. METHODS: This was a prospective study conducted at
      an urban HEMS program with flight nurse/flight paramedic staffing and protocol
      driven care. There were 200 consecutive cases undergoing HEMS ETI between April
      2004 and July 2005. Univariate logistic regression with odds ratio (OR) was used
      to assess for association between ETI-related hypoxemia (decrease in SpO2 value
      to < 90% during ETI) and patient/intubator characteristics. RESULTS: HEMS crew
      ETI was successful in 189 (95.4%) of the 200 patients. The lowest peri-ETI SpO2
      value was specifically documented in 170 patients (85%) in the study group. In
      univariate analysis, successful crew ETI was correlated with avoidance of crew
      recorded SpO2 value decreasing to < 90% (OR, 0.23; 95% confidence interval, 0.07
      0.83). Similarly, requirement for multiple attempts at ETI was correlated with
      higher likelihood that crews recorded peri-ETI SpO2 value decreasing to < 90%
      (OR, 7.8; 95% confidence interval, 3.2-18.8). However, in nearly two thirds of
      cases in which multiple attempts were executed, the peri-ETI SpO2 value remained
      > 90%. Of the seven patients in whom rescue laryngeal mask airways were placed,
      the peri-ETI SpO2 value remained > 90% in three (42.9%). CONCLUSION:
      Documentation of crew-recorded peri-ETI SpO2 nadir is a useful and practical
      prehospital data point.

PMID- 16801284
TI  - The in-hospital interval: a description of EMT time spent in the emergency
      department.
AB  - OBJECTIVE: We conducted a time-motion study of emergency medical technician (EMT)
      flow in an urban, academic emergency department (ED). Our objective was to
      describe the activity of the EMTs during their time in the ED. Secondary
      objectives included the association of time of day, age, and triage code with the
      various time intervals. METHODS: In this descriptive study, we combined
      information from two databases: prospectively collected time-motion data of EMTs
      presenting to one ED and an electronically collected prehospital call database of
      time data. The pretriage, triage, and posttriage time intervals were calculated,
      as well as total time spent in the ED as a proportion of total call time. Mean
      times with 95% confidence intervals (CIs) were reported. Analysis of variance was
      performed to examine the associations of time of day, age, and triage code with
      time intervals. RESULTS: Data were available for 152 calls. The mean pretriage
      interval was 8.79 (95% CI, 7.55-10.04) minutes, the mean triage interval was 5.14
      (95% CI, 4.49-5.79) minutes, and the mean posttriage interval was 31.33 (95% CI,
      29.08-33.58) minutes. The proportion of the total call time that was spent in the
      ED was 45%. Subgroup analysis showed significant differences only between total
      time spent in the ED in the 7:30-10:00 AM period as compared with the other
      periods. CONCLUSIONS: More time was spent in the pretriage and posttriage
      intervals as compared with the triage interval. Further time-motion studies in
      the ED will be necessary to plan interventions aimed at decreasing the time spent
      in-hospital by EMTs.

PMID- 16801283
TI  - Prehospital 12-lead ECG: efficacy or effectiveness?
AB  - INTRODUCTION: Previous literature has documented that prehospital 12-lead
      electrocardiography (ECG) decreases the time to reperfusion in patients with an
      acute ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: To compare
      time to ECG, time to angioplasty suite (laboratory), and time to reperfusion in
      emergency medical services (EMS) STEMI patients, who received care through three
      different processes. METHODS: The setting was a large suburban community teaching
      hospital with emergency department (ED)-initiated single-page acute myocardial
      infarction (AMI) team activation for STEMI patients. The population was STEMI
      patients transported by EMS from January 2003 to October 2005. Not all EMS
      agencies had prehospital 12-lead ECG capability. Paramedics interpret and
      verbally report clinical assessment and ECG findings via radio. The AMI team is
      activated at the discretion of the emergency physician 1) before patient arrival
      to the ED based on EMS assessment, 2) after ED evaluation with EMS ECG, or 3)
      after ED evaluation and ED ECG. Time intervals were calculated from ED arrival.
      To assess the impact of interventions on performance targets, we also report the
      proportion of patients who arrived in laboratory within 60 minutes and
      reperfusion within 90 minutes of arrival. Parametric and nonparametric statistics
      are used for analysis. RESULTS: During the study period, there were 164 STEMI
      patients transported by EMS; mean age was 66.1 years, and 56% were male. Of
      these, 93 (56.7%) had an EMS ECG and 31 (33%) had AMI team activation before ED
      arrival. Mean time to laboratory for all patients was 49.8 +/- 34.4 minutes and
      time to reperfusion was 93.2 +/- 34.5 min. Patients with prearrival activation
      were transported to laboratory sooner (mean, 24.3 vs. 53. 4 minutes; p < 0.001)
      and received reperfusion sooner than all other patients (mean, 70.4 vs. 96.3
      minutes; p = 0.007). More prearrival activation patients met performance targets
      to laboratory (96.7% vs. 73.7%; p = 0.009) and reperfusion (85.2% vs. 51.0%; p =
      0.003). There was no difference in time to laboratory or to reperfusion for
      patients who received EMS ECG but no prearrival activation compared with those
      who received EMS transport alone. CONCLUSIONS: A minority of patients with EMS
      ECGs had prearrival AMI team activation. EMS ECGs combined with systems that
      activate hospital resources, but not EMS ECGs alone, decrease time to laboratory
      and reperfusion.

PMID- 16801285
TI  - Performance analysis of a medical decision algorithm to mitigate spread of SARS
      due to interfacility patient transfers.
AB  - OBJECTIVE: To determine performance of a medical decision algorithm to mitigate
      spread of severe acute respiratory syndrome (SARS) from interfacility patient
      transfers during the Toronto SARS outbreak. METHODS: Records from the Provincial
      Transfer Authorization Centre and Toronto Public Health from April 1 to July 31,
      2003, were linked using probabilistic methods. Authorization decision (transfer
      authorized or denied) and SARS status (probable case, suspect case, or patient
      under investigation for SARS; or non-SARS case) were obtained for linked records.
      Primary outcome was the number of patients where correct authorization decisions
      were made based on SARS status at the time of request. Secondary outcome was the
      number for whom, in retrospect, authorization decision was correct knowing final
      SARS status. Algorithm sensitivity, specificity, and predictive values were
      determined. RESULTS: There were 14,571 requests for transfer and 2,132 patients
      investigated for SARS during the study period. The algorithm authorized 14,551
      and did not authorize 20 requests. Sensitivity and specificity to make
      appropriate authorization decisions at the time of request were 100% (95%
      confidence interval [CI], 77.2%-100%) and 99.95% (95% CI, 99.9-100%),
      respectively. Positive and negative predictive values were 65% (95% CI, 44.1%
      85.9%) and 100% (95% CI, 98.4%-100%), respectively. Sensitivity and specificity,
      in retrospect, within ten days of the transfer request were 100% (95% CI, 80.6%
      100%) and 99.97% (95% CI, 99.9%-100%), respectively. Positive and negative
      predictive values were 80% (95% CI, 62.5%-97.5%) and 100% (95% CI, 98.4%-100%),
      respectively. Seven of the 20 patients with nonauthorized requests were not known
      to have SARS at the time of request. Within ten days, three of seven were under
      investigation for, a suspect case of, or a probable case of SARS. CONCLUSIONS:
      The medical decision algorithm was highly sensitive and specific in correctly
      authorizing transfers. Despite its highly sensitive and specific algorithm, it
      did incorrectly deny authorization to a very small number of patients without
      SARS.

PMID- 16801286
TI  - Evaluating an emergency medical services-initiated nontransport system.
AB  - OBJECTIVE: To evaluate both factors predicting nontransport and mortality rates
      in an emergency medical services system with a nontransport policy. METHODS: We
      reviewed data from 1,581 transported and nontransported patients from October
      2001 to July 2003. Patients who refused transport against medical advice were
      excluded. Extracted data included demographics, run characteristics, chief
      complaint, and clinical impression. Transported and nontransported patients were
      compared using Mann-Whitney U or chi-square tests. Logistic regression identified
      factors predictive of nontransport. A Social Security Death Index search
      determined 30-day mortality. RESULTS: A total of 1,501 runs involving 1,059
      patients were included. Median age was 60 years (range, 0-97 years). A total of
      427 (40.4%) were male; 107 (10.2%) were nonwhite. Older patients were more likely
      to be transported (odds ratio, 1.03; confidence interval, 1.02-1.03). Race,
      frequency of calls, mutual aid, or time of day did not significantly influence
      probability of transport. Patients with cardiovascular, respiratory, and
      gastrointestinal complaints were more likely to be transported than those with
      other conditions (P < 0.005); patients with endocrine, trauma, and miscellaneous
      complaints were less likely to be transported (P < 0.003). Patients with renal,
      obstetrics/gynecology, and hema matology/oncology were complaints all
      transported. Mortality was 4.9% (confidence interval, 3.9%-6.2%) for transported
      patients and 1.0% for those not transported (confidence interval, 0.2%-3.7%).
      CONCLUSIONS: Age is a determinant when deciding on transporting patients.
      Patients with complaints with potentially higher acuity were transported most
      often. Only two nontransported patients died within 30 days, although it is
      unknown whether initial transport would have changed their mortality. Our data
      suggest that emergency medical services-initiated nontransport is influenced only
      by age and chief complaint and may not result in significant mortality.

PMID- 16801287
TI  - Paramedic compliance with ACLS epinephrine guidelines in out-of-hospital cardiac
      arrest.
AB  - OBJECTIVE: The purpose of this observational study was to determine the baseline
      rate of adherence to current American Heart Association guidelines with regard to
      use of epinephrine in out-of-hospital cardiac arrests. METHODS: A structured
      explicit retrospective review of all adult victims of cardiac arrest logged in
      the EMSCQI.com database during its first 20 months in operation from February
      2004 to October 2005. Noncompliance was defined as epinephrine administration on
      average less than every three minutes or greater than every five minutes
      regardless of dosage. Primary determination of noncompliance was calculated by
      dividing the time from first epinephrine dose to hospital arrival by the number
      of subsequent doses given during that time frame. RESULTS: Seventy-five of 11,000
      advanced life support calls were identified as out-of-hospital cardiac arrests.
      The overall rate of noncompliance was 86% (95% confidence interval, 75-93%). The
      average time from the first epinephrine administration to hospital arrival was
      22.6 minutes. The median number of epinephrine doses per patient was three. All
      patients in the noncompliant group received epinephrine less often than every
      five minutes. The data did not allow for examination of noncompliance predictors.
      CONCLUSIONS: Epinephrine administration in accordance with current advanced
      cardiac life support guidelines occurred in 14% of out-of-hospital cardiac arrest
      patients.

PMID- 16801288
TI  - Determination of infant-safe homes in a community injury prevention program.
AB  - BACKGROUND: The home is the most common site of childhood injury. To address this
      problem, Orange County Emergency Management developed the novel "Welcome to the
      World" program to provide paramedic-delivered home safety inspections and
      interventions to improve early childhood safety. OBJECTIVES: To determine the
      prevalence of infant-safe homes and to examine differences in home infant safety
      based on the number of children in the home. METHODS: Paramedics visited
      households with newborns or expectant mothers for a home visit at their request.
      Each visit included a home safety inspection, correction of certain safety
      practices, one-on-one teaching of injury prevention topics, and distribution of
      educational materials and safety devices. A retrospective analysis of data
      recorded during these visits included criteria used in defining an infant-safe
      home, including 1) presence of a functioning smoke detector, 2) bathwater
      temperature measured < 120 degrees F, 3) correct crib slat spacing, and 4)
      presence of a car seat. RESULTS: Paramedics conducted 110 home visits, of which
      57% were first-time parents. Only 33% (n = 10) of multiple-child homes and 38% (n
      = 14) of one-child homes were defined as infant safe by meeting all four
      criteria. CONCLUSIONS: An alarmingly low number of homes were infant safe (n =
      24) and the number of children in the home did not seem to affect home safety.
      Further research is needed to determine the efficacy of the "Welcome to the
      World" program.

PMID- 16801289
TI  - Intermittent bolus dosing of lidocaine in emergency medical services-an
      alternative to bolus followed by a drip.
AB  - OBJECTIVE: To determine the effectiveness and safety, in an emergency medical
      services setting, of intermittent bolus dosing of lidocaine versus a bolus
      followed by a drip. METHODS: This was a prechange and postchange observational
      study, following a protocol change. Patients 18 years or older treated with
      lidocaine for cardiac dysrhythmia were included in the study. Patients were
      excluded for lidocaine for intubation, cardiac arrest without return of
      spontaneous circulation, trauma, interhospital transport, and incomplete charts.
      Patients were divided into two groups. The drip group (January 1, 2002, to
      January 14, 2003) was treated with lidocaine 1.0-1.5 mg/kg intravenous bolus up
      to 3 mg/kg until the dysrhythmia resolved and then a 2-4 mg/min drip. The bolus
      group (January 15, 2003 to December 31, 2003) was treated with lidocaine 1.5
      mg/kg intravenous bolus, followed by 0.75 mg/kg bolus every five minutes up to 3
      mg/kg until the dysrhythmia resolved; once the dysrhythmia resolved, intermittent
      boluses of 0.75 mg/kg every 10 minutes were adminstered. Outcome variables
      studied were maintenance of rhythm of nonventricular origin, occurrence of
      complications, and adherence to written protocols. Complications considered were
      seizures, respiratory depression, and cardiac arrest. RESULTS: The study included
      146 patients in the drip group and 113 patients in the bolus group. Overall, 119
      of 146 patients (81.5%) in the drip group and 101 of 113 patients (89.3%) in the
      bolus group maintained a rhythm of nonventricular origin (p = 0.079). There was
      no statistical difference between the two groups in complications or protocol
      variance: one of 146 patients (0.7%) in the drip group and one of 113 patients
      (0.9%) in the bolus group had a serious complication; 64 of 146 patients (43.8%)
      in the drip group and 54 of 113 patients (47.8%) in the bolus group had a
      protocol variance. CONCLUSIONS: Intermittent bolus dosing protocol was associated
      with an equivalent effectiveness in maintaining rhythms of nonventricular origin
      without an increase in complications.

PMID- 16801292
TI  - Assessing tobacco dependence: a guide to measure evaluation and selection.
AB  - Tobacco dependence is a key construct in tobacco research. This paper describes a
      construct validation approach to dependence assessment and describes key
      conceptual and psychometric criteria on which to evaluate putative measures of
      dependence. Five current dependence scales-the Fagerstrom Test for Nicotine
      Dependence; the Diagnostic and Statistical Manual of Mental Disorders (4th ed.);
      the Cigarette Dependence Scale; the Nicotine Dependence Syndrome Scale; and the
      Wisconsin Inventory of Smoking Dependence Motives-are examined with respect to
      these critical dimensions. Recommendations are made regarding the use of each
      measure.

PMID- 16801293
TI  - Correlates of home smoking restrictions among rural smokers.
AB  - The prevalence of smoking is greater and smoking restrictions are less common in
      rural areas in comparison to urban areas. Consequently, rural smokers and their
      families are at increased risk for adverse health consequences from smoking. The
      presence of home smoking restrictions (i.e., limiting or banning cigarette
      smoking in the home) can be a mediator for smoking cessation and can reduce
      health risks for those who live with smokers. The purpose of the present study
      was to identify correlates of home smoking restrictions among rural smokers. We
      surveyed 472 smokers from 40 rural Kansas primary care practices who were
      enrolled in a smoking cessation intervention study. We assessed the prevalence of
      home smoking restrictions and examined the relationship between such
      restrictions, demographic variables, comorbid diagnoses, and psychosocial
      measures of smoking abstinence self-efficacy and motivation to quit. Complete
      home smoking restrictions were found among 25.4% of rural smokers with an
      additional 28.3% reporting some restrictions. Restrictions were associated with
      younger age, higher controlled motivation to quit (i.e., motivation from external
      pressure), the presence of children under age 6 years living in the home, fewer
      friends who smoke, and a partner who does not smoke. Smokers with a comorbid
      diagnosis of high cholesterol, chronic lung disease, or heart disease were less
      likely to have restrictions. Most smokers in rural primary care practices do not
      have home smoking restrictions, particularly those without children or a
      nonsmoking partner and those with significant risk factors for smoking-related
      illnesses. These patients may be critical targets for broaching issues of home
      smoking restrictions.

PMID- 16801294
TI  - A psychometric evaluation of cigarette stimuli used in a cue reactivity study.
AB  - Laboratory studies have demonstrated that cigarette smokers react with
      significant subjective and autonomic responses (e.g., increased craving and
      increased heart rate) in the presence of stimuli associated with smoking.
      Although cue reactivity effects are typically robust, a number of methodological
      considerations make interpretation and design of cue reactivity studies
      problematic. Previous research has paid scant attention to the psychometric
      properties of the cigarette cues presented, and standard cues would enhance
      comparison and synthesis of studies. In the present study, we evaluated 12
      cigarette photos (compared with positive, negative, and neutral photos), used in
      a separate study, for their ability to evoke self-report of craving in both
      nicotine-deprived and nondeprived smokers. These photos performed as expected,
      with cigarette pictures evoking significantly higher craving than neutral
      pictures and deprived smokers showing a trend toward higher craving than
      nondeprived smokers. The cigarette picture set was evaluated for internal
      consistency (Cronbach's alpha = .97) as a 12-item scale and further reduced to
      multiple 2-item scales with reliability estimates ranging from .70 to .93. A
      cluster analysis of all pictures showed that, when rated for craving, cigarette
      pictures clustered together, indicating they had distinct properties compared
      with positive, negative, and neutral pictures. Effect sizes were calculated for
      each cigarette picture in both deprived and nondeprived smokers. The craving
      effect sizes ranged from .57 to .98 for nondeprived smokers, and from .61 to .99
      for deprived smokers. The analyses suggest these cigarette pictures have
      excellent psychometric properties for use in future cue reactivity studies.

PMID- 16801295
TI  - The long-term effect of local policies to restrict retail sale of tobacco to
      youth.
AB  - Many adolescent smokers rely significantly on retail tobacco sources to initiate
      or maintain their smoking behavior. Though promising, the results from various
      interventions aimed at curtailing retail tobacco access have been mixed. In the
      present study, 14 communities were randomly assigned to intervention and control
      groups in an attempt to determine the long-term effect of local youth access laws
      and policies on adolescent smoking. The intervention continued for 32 months.
      Assessments were conducted at baseline (1991) and at years 3, 5, and 7. The
      intervention was based on a community-organizing approach that mobilized
      community members to support adoption and enforcement of local ordinances to
      restrict minors' access to commercial sources of tobacco. The major outcome
      measure for the study was cross-sectional prevalence of daily tobacco use among
      all students in grades 8, 9, and 10 in each community, measured by a self
      administered student survey. A short-term significant intervention effect was
      observed and reported previously. That difference between intervention and
      control communities was maintained through the year 5 assessment but had
      dissipated by the year 7 assessment, very likely related to adoption of
      ordinances by control communities. Restricting commercial access to tobacco
      through local ordinances is effective in reducing adolescent smoking both
      immediately after the intervention (year 3) and 2 years later (year 5). Longer
      term results are still inconclusive, because control communities adopted
      ordinances similar to those in the intervention communities.

PMID- 16801296
TI  - The effects of smoking deprivation and nicotine administration on emotional
      reactivity.
AB  - Although converging lines of evidence suggest that nicotine and mood are related
      at a fundamental biological level, this link has not been reliably demonstrated
      in laboratory studies. In this study, startle probe methodology was used to
      examine the effects of nicotine administration and deprivation on emotional
      processes associated with motivation. Smokers (N = 115) completed four laboratory
      sessions crossing deprivation (12-hr deprived vs. nondeprived) with nicotine
      spray (active vs. placebo). Participants viewed affective pictures (positive,
      negative, neutral) and pictures involving cigarette cues, while startle probes
      were administered. Deprivation decreased startle responding to cigarette cues,
      suggesting an activation of appetitive processes. Nicotine administration
      suppressed overall startle responding during deprivation. In addition, during
      deprivation, random exposure to negative stimuli over two blocks of trials
      resulted in decreased adaptation of the startle response, suggesting that some
      sensitization to negative emotional cues may take place during nicotine
      withdrawal. These effects are consistent with formulations of addiction,
      stressing that withdrawal may both increase the reinforcement salience of smoking
      stimuli and decrease habituation to negative emotional stimuli.

PMID- 16801297
TI  - Changes in health care costs before and after smoking cessation.
AB  - Previous research on health care costs among former smokers suggests that
      quitters incur greater health care costs for up to 4 years after cessation
      compared with continuing smokers. However, little is known about the relationship
      between health care costs and utilization in the periods before as well as after
      cessation. The present study used a retrospective cohort design with automated
      health plan and primary data to examine the health care costs and clinical
      experiences before and after smoking cessation among former smokers compared with
      a sample of continuing smokers. Subjects were a random sample of adults (aged 25
      and older) whose smoking status was identified by a physician during a primary
      care visit to the Group Health Cooperative (GHC), a nonprofit, integrated health
      care delivery system in western Washington state. Total direct health care costs
      among former smokers began to rise in the quarter prior to cessation and were
      significantly greater (p < .001) than those of continuing smokers in the quarter
      immediately following cessation. This difference dissipated within one quarter
      following cessation. We replicated the postquit cost spike among former smokers
      found by other research and showed that this spike dissipated within the first
      year postquit. Smoking cessation did not result in sustained cost increases among
      former smokers.

PMID- 16801298
TI  - Are menthol cigarettes a starter product for youth?
AB  - This study assessed the relationship between menthol use and nicotine dependence.
      Data from the National Youth Tobacco Survey indicated that menthol cigarette use
      was significantly more common among newer, younger smokers. Additionally, youth
      who smoked menthol cigarettes had significantly higher scores on a scale of
      nicotine dependence compared with nonmenthol smokers, controlling for demographic
      background and the length, frequency, and level of smoking. The study suggests
      that menthol cigarettes are a starter product that may be associated with smoking
      uptake by youth.

PMID- 16801299
TI  - Does a failed quit attempt reduce cigarette consumption following resumption of
      smoking? The effects of time and quit attempts on the longitudinal analysis of
      self-reported cigarette smoking intensity.
AB  - California Tobacco Survey respondents were asked the intensity of their cigarette
      smoking 1 year previously and at the time of the survey. Respondents reported a
      generally lower smoking intensity at survey time compared with 1 year previously.
      Multivariable statistical models on the change in smoking intensity in the past
      year were fitted to assess the effects of low-tar cigarette use, a quit attempt
      in the past year, smoking intensity 1 year previously, and demographic variables
      (age, education, income, and race). The most important predictor of change in
      intensity was the intensity 1 year previously. The next most important predictor
      was whether a quit attempt had been made in the previous year. The demographic
      variables also were found to have a significant effect, although their effects
      were of smaller magnitude. Low-tar cigarette use was not a significant predictor
      of change in intensity in multivariable analysis. The effect of a quit attempt on
      the reduction in intensity of smoking suggests that periods of cessation may
      reduce the intensity of smoking and the level of addiction for several months
      following relapse. Consequently, it may be important to control for cessation
      activity in studies comparing exposures from conventional tobacco products to
      exposures from new products that purport to offer lower harm.

PMID- 16801300
TI  - Effects of information processing load in abstinent and nonabstinent smokers'
      psychomotor task performance.
AB  - Recent evidence has indicated that nicotine, the active agent in tobacco, may
      affect mental abilities of smokers. To better understand the effects of nicotine
      on central processing, we used a basic chronometric approach to studying
      information processing. This chronometric approach allowed for the independent
      examination of nicotine's effects on two theoretically nonoverlapping information
      processing stages, stimulus identification and response programming. Two stimulus
      intensity and four distance traversed conditions were used to affect the stimulus
      identification and response programming stages, respectively. The 11 subjects
      completed two experimental sessions (nicotinized and denicotinized), which were
      conducted 1 week apart. Each experimental session comprised two tests. The first
      test consisted of abstinent baseline measures, and the second test was
      administered after subjects smoked an investigator-supplied nicotinized or
      denicotinized cigarette. Data analysis revealed that the higher intensity
      stimulus elicited faster reaction times, as did the shorter movement distances,
      thus confirming successful manipulation of both the stimulus identification and
      response programming stages of the information-processing model. Furthermore, the
      significant improvement in reaction-time performance over baseline abstinent
      levels was consistent despite the manipulations made within the stimulus
      identification stage of processing, demonstrating that no interaction existed
      between stimulus intensity and the administration of nicotine. Interestingly,
      these data provide initial evidence that although nicotine may not affect the
      programming of very simple movements, it has a more pronounced effect on more
      complex movements. Although distance traversed had a reliable effect on movement
      time, nicotine had no observable effect.

PMID- 16801301
TI  - Attitudes and knowledge about nicotine and nicotine replacement therapy.
AB  - Nicotine replacement therapies (NRTs) represent an effective means of promoting
      smoking cessation, but they remain underutilized. Negative attitudes and false
      beliefs about nicotine and nicotine replacement may cause NRT underutilization.
      In a randomized, controlled, single-blind study of nicotine gum, 97 smokers were
      assessed on their attitudes and knowledge about nicotine, nicotine replacement,
      and smoking cessation therapy. Information from these self-report measures was
      used in an intervention that provided tailored, brief feedback to promote
      positive attitudes and accurate knowledge about NRT. Considerable variability in
      pretreatment attitudes and knowledge was observed across individuals. Moreover,
      attitudes and knowledge showed a consistent pattern of intercorrelation and were
      systematically related to smoking characteristics (e.g., prior use of NRT,
      nicotine dependence, treatment completion). The brief feedback intervention led
      to a significant global elevation in attitudes about nicotine, NRT, and assisted
      cessation but not knowledge about nicotine. Changes in attitudes and knowledge
      were not significantly related to gum use or smoking cessation. Recommendations
      for the appropriate application of brief feedback are offered.

PMID- 16801302
TI  - Adolescent smokers screened for a nicotine replacement treatment trial:
      correlates of eligibility and enrollment.
AB  - The enrollment process determines the study sample and external validity of
      clinical trial results; however, few reports describe the process and outcome of
      screening efforts for smoking cessation studies among adolescents. We describe
      and evaluate a screening protocol to enroll adolescent smokers for a randomized
      clinical trial of nicotine replacement therapy. Adolescent smokers obtained the
      recruitment call-in number (1-800-NO-SMOKE) via media and other advertisements.
      Trained recruitment staff collected information using an internally developed,
      targeted telephone screening interview, which was used to determine pre
      eligibility for the clinical trial. Correlates of qualification and of study
      enrollment were determined. Among 1,347 adolescents screened, 329 (24.4%) were
      eligible to participate in the trial. Light smoking (39.1%) and lack of parental
      support (14.8%) were the biggest contributors to ineligibility. Eligible
      adolescents were more likely to be female (66.9% vs. 58.2%, p = .0052) and more
      likely to be European American (63.5% vs. 52.2%, p = .0003). The higher rates of
      ineligibility for African Americans and boys were partly explained by lower
      scores on the Fagerstrom Test for Nicotine Dependence. Of those eligible to
      participate in the trial, 159 (48.3%) enrolled. Results underscore the need for
      screening instruments that are measurement-invariant across ethnicities and
      gender, and for enrollment strategies that maximize inclusion of eligible
      participants.

PMID- 16801303
TI  - Longitudinal effects of pro-tobacco and anti-tobacco messages on adolescent
      smoking susceptibility.
AB  - We examined the longitudinal impact of self-reported exposure to pro- and anti
      tobacco media on adolescents' susceptibility to smoking, using in-school surveys
      from a culturally diverse sample. Ethnicity and acculturation also were examined
      as potential moderators. Middle-school students (N = 2,292) completed self-report
      questionnaires during the 6th, 7th, and 8th grades. Chi-square analyses were
      conducted to determine whether reported exposure to pro- and anti-tobacco media
      varied according to ethnicity, acculturation, and immigration status. Logistic
      regression models were used to examine whether pro- and anti-tobacco media
      exposure in 6th grade was associated with susceptibility to smoking by later
      grades. Recall of people smoking in television programs and pro-tobacco
      advertisements in stores was associated with adolescent smoking susceptibility.
      Exposure to anti-tobacco advertisements on television protected against
      susceptibility. No significant interaction effects between pro- and anti-tobacco
      media exposure on smoking susceptibility were found. Ethnicity and acculturation
      did not moderate these associations. Our longitudinal study provides evidence
      that pro-tobacco media and advertising increases susceptibility to smoking over
      time. More important, anti-tobacco advertisements are not sufficient to reduce
      the harmful effects of adolescent exposure to pro-tobacco media. Policy-level
      interventions such as restrictions in tobacco advertising may be necessary to
      prevent adolescent smoking.

PMID- 16801304
TI  - Consequences of marketing exceptions in the Master Settlement Agreement: exposure
      of youth to adult-only tobacco promotions.
AB  - The Master Settlement Agreement between a consortium of tobacco companies and 46
      states contains many restrictions on tobacco sales and advertising that were
      designed to reduce youth exposure to tobacco promotions. Most of the restrictions
      include an exception for "adult-only" facilities. The present study investigated
      the extent to which youth are being exposed to marketing that is presumably
      limited to adults. Using data from a statewide random-digit-dialed survey of
      3,863 Massachusetts youth aged 12-17 years, we found that about half of all youth
      in this age group reported seeing cigarettes advertised at events, concerts,
      bars, or clubs in the past 12 months, and that about 5% of youth in this age
      group reported being present at a venue where free samples of cigarettes were
      being distributed. Youth exposed to this marketing were those most at risk for
      progression to established smoking. To our knowledge, this is the first study to
      estimate youth exposure to advertisements designed for adult-only venues. In
      light of the large body of evidence that exposure to tobacco advertising and
      promotion increases tobacco use among youth, our findings demonstrate the need to
      close the "adult-only" loophole.

PMID- 16801305
TI  - Brief report: pain and readiness to quit smoking cigarettes.
AB  - This study explored the relationship between smoking and significant pain. It was
      hypothesized that readiness to quit smoking would be negatively affected by pain
      issues. A cross-sectional design was used in this phone-based survey with
      randomly selected adult smokers. A total of 307 adult participants in the control
      group from a larger Quit and Win Study participated in the interview.
      Participants were contacted at home and completed a 20-min phone survey including
      measures of pain, stress, depressive symptoms, social support, tobacco use
      status, and readiness to quit smoking. A total of 28% reported significant pain
      in the past week. Participants who experienced significant pain smoked more
      cigarettes per day than those who did not report significant pain. However, pain
      was not associated with readiness to quit. More than half (58%) of those with
      significant pain were in the contemplation stage of change or higher. The fact
      that smokers with pain were just as likely as those without significant pain to
      be ready to quit demands that each individual patient with pain be assessed for
      readiness to quit so that a tailored approach can be adopted either to motivate
      the patient to quit or to assist the patient with evidence-based tobacco
      dependence treatment strategies if he or she wants such treatment. Placing formal
      tobacco dependence treatment programs within pain clinics and addressing pain in
      smoking cessation programs is recommended.

PMID- 16801306
TI  - The twentieth century: The century of progress and medicine.

PMID- 16801307
TI  - The potential for the use of insulin lispro in pregnancy complicated by diabetes.
AB  - The target of improved perinatal outcome in diabetic pregnancies may be achieved
      by new insulin preparations that more closely mirror the physiological response
      of insulin and not exclusively the traditional means of strict adherence to diet
      and frequent blood glucose testing.No insulin preparation has been systematically
      tested in pregnancy; it is a responsibility of all clinicians who look after
      pregnant diabetic women to record the outcomes of IL-treated pregnancies. More
      data is needed before this preparation can be either recommended in pregnancy or
      alternatively avoided.

PMID- 16801308
TI  - The interval to spontaneous delivery following discontinuation of maintenance
      tocolysis.
AB  - OBJECTIVE: To determine the interval to spontaneous delivery following
      discontinuation of continuous subcutaneous terbutaline (SQT). METHODS: Singleton
      and twin gestations receiving outpatient preterm labor management services with
      SQT were identified from a database. Patients having SQT discontinued at 33.0
      35.9 weeks (in a stable condition, not hospitalized and with known cervical
      status at discontinuation) with subsequent spontaneous labor and delivery were
      included (n = 1420). Data were compared by gestation type, week of SQT
      discontinuation and cervical dilatation using Kruskal-Wallis and Fisher's exact
      test analyses (p < 0.05 statistically significant). RESULTS: Spontaneous preterm
      delivery occurred in 63.0% of singletons and 87.9% of twins. Although stable at
      SQT discontinuation, 32.5% of singletons and 59.9% of twins delivered within
      three days. The interval from discontinuation of SQT to delivery was less for
      twin than singleton gestations (5.1 +/- 6.5 vs. 11.0 +/- 10.5 days, respectively,
      p < 0.001). CONCLUSIONS. Preterm discontinuation of SQT should be avoided if
      additional pregnancy prolongation is desired.

PMID- 16801309
TI  - Non-invasive fetal sex determination using real-time PCR.
AB  - OBJECTIVE: The aim of this study was to evaluate the specificity and sensitivity
      of the real-time quantitative PCR method for fetal gender determination in early
      pregnancy. METHODS: Blood samples were collected from 46 pregnant women prior to
      amniocentesis. DNA was extracted from maternal plasma using a QIAmp DNA Blood
      Mini Kit. DNA samples were subjected to real-time quantitative PCR amplification
      of SRY (as a fetus-specific marker) and beta-globin (as a marker for total plasma
      DNA) genes. RESULTS: The beta-globin gene sequence was detected in all samples.
      The SRY gene was detected in 25 of 28 plasma samples from women with male fetuses
      and in none of the 18 samples from women with female fetuses (sensitivity 89.2%
      and specificity 100%). The fetal gender was correctly determined in 43 (93.5%) of
      46 maternal plasma samples. The concentration of the beta-globin gene ranged from
      161 to 25,568 genome-equivalents (GE)/mL (median 1051.1), while the concentration
      of the SRY gene ranged from 5 to 166 GE/mL (median 27.4). The percentage of free
      fetal DNA ranged from 0.1% to 46.1% (median 2.0%). CONCLUSION: Amplification of
      fetal DNA from maternal plasma by real-time quantitative PCR is a promising
      method for fetal sex determination in early pregnancy. However, further studies
      are necessary before this procedure can be included into a clinical routine.

PMID- 16801310
TI  - Lack of effect of dietary nucleotide supplementation on erythrocyte 2,3
      diphosphoglycerate concentration. A study on preterm neonates.
AB  - BACKGROUND: Recently we demonstrated an increased 2,3-diphosphoglycerate (2,3
      DPG) erythrocyte concentration in rat pups subjected to nucleotide-enriched
      artificial feeding. DESIGN: The present study was carried out to test the
      hypothesis that a possible increase in 2,3-DPG concentration can also be obtained
      in human neonates who are fed nucleotide-enriched formula. Preterm neonates born
      or referred to the neonatal intensive care unit of the G. Gaslini Hospital, Genoa
      University, with a gestational age >30 weeks and <37 weeks were enrolled in our
      randomized trial. Recruitment took place within 48-72 hours from birth. Only
      newborns of mothers deciding not to breast-feed were eligible to be randomized
      for the supplemented group (FN) or non-supplemented group (RF). Breast-fed
      newborns were considered the control group (C). The study window (for
      supplementation and blood samples) was restricted to the first two weeks
      following birth (from the 2nd (t1) to the 16th (t2) day of life). At the end of
      our study, only 21 neonates were eligible for statistical analysis. RESULTS: The
      stimulating action of dietary nucleotides on 2,3-DPG concentration failed to be
      demonstrated; increases in 2,3-DPG concentration that were observed in newborns
      fed with nucleotide supplemented formula (FN) were comparable to those observed
      in newborns fed with regular formula (RF) and breast-fed newborns. CONCLUSIONS:
      The EC recommendation for the amount of nucleotides allowed in formula milk does
      not seem to be high enough to have positive effects on 2,3-DPG synthesis. Whether
      this possible 'pharmacological' effect can be achieved by a higher intake of
      ingested nucleotides and/or a change in the proportions of single nucleotides
      contained in milk formulas remain interesting end points to be elucidated.

PMID- 16801311
TI  - Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic
      pregnancies in the intrauterine normal and growth-restricted fetus.
AB  - OBJECTIVE: The aim of this study was to carry out a comparative analysis of the
      maternal and umbilical cord TNFalpha serum levels in pregnancies complicated by
      severe preeclampsia with normal intrauterine fetal growth, in preeclamptic
      pregnancies with intrauterine growth restriction (IUGR), and in normotensive
      pregnant patients. PATIENTS AND METHODS: The study was carried out on eight
      patients with severe preeclampsia complicated by IUGR and 18 preeclamptic
      patients with normal intrauterine fetal growth. The control group consisted of 18
      healthy normotensive patients with singleton uncomplicated pregnancies. Maternal
      and umbilical serum TNFalpha concentrations were estimated using a sandwich ELISA
      assay. RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had
      significantly higher maternal and umbilical serum TNFalpha levels than those in
      the normotensive controls. Our findings and other reports indicate that TNFalpha
      may participate in the pathogenesis and sequelae of preeclampsia with and without
      IUGR. The results of excessive umbilical serum activity of tumor necrosis factor
      alpha (TNFalpha) in preeclamptic pregnancy complicated by intrauterine growth
      restriction (IUGR) may suggest additional changes and dysfunction of the
      placental-fetal unit and deterioration of placental function, leading to fetal
      hypotrophia in the course of preeclampsia.

PMID- 16801312
TI  - Maternal mortality rates in the last eight years: A university hospital-based
      study from Turkey.
AB  - OBJECTIVE: To analyze the cause of changing maternal mortality ratios (MMRs) in a
      tertiary women's health center in Turkey in the last eight years. MATERIALS AND
      METHODS: Charts of patients seen between 1998 and 2005 were retrospectively
      reviewed. Statistical analysis was performed using the Chi-square test. The
      results were accepted to be significant when the p value was <0.05. RESULTS:
      During this period, 27 pregnancy-related deaths were identified via hospital
      death records. The MMR was found to have decreased in rate by approximately 50%
      from 822.2/100,000 live births in the previous report including the years 1978
      1997 to 412.0/100,000 during the last eight years (p < 0.01). Pregnancy-induced
      hypertension was still the most frequent cause of maternal death. The decrease in
      MMR was due to the decrease in the ratio of maternal infection (26.4% in 1978
      1997 to 7.4% in 1998-2005, p < 0.01). CONCLUSION: Although treatment in the
      antenatal care and health service has decreased maternal deaths, it was
      discovered that the MMR has not reached the optimum levels found in developed
      countries in the last eight years. Also the percentage of direct obstetric deaths
      (with the exception of those caused by infection) showed no change and was
      similar to that found in the previous report (1978-1997).

PMID- 16801313
TI  - Assessing the relationship between preterm delivery and various microorganisms
      recovered from the lower genital tract.
AB  - OBJECTIVE: To determine if the likelihood of preterm delivery is more dependent
      on the specific organisms present in the vagina than on the presence of bacterial
      vaginosis. METHODS: We evaluated the vaginal fluid of a prospective cohort of
      women at 23-32 weeks of gestation with signs and symptoms of preterm labor and
      intact membranes. Forward stepwise logistic regression models were used to
      evaluate the relationship between preterm delivery and the presence of anaerobic
      bacteria, Gardnerella, ureaplasmas and mycoplasmas, and sialidase. RESULTS: The
      cohort included 137 women, and complete delivery information was available for
      134 of them. The rate of preterm delivery was 28% (37 of 134). Mycoplasma
      genitalium independently was associated with spontaneous preterm delivery (OR
      3.48; 95% CI 1.41, 8.57). After controlling for this factor, none of the other
      variables were significantly prognostic for spontaneous preterm delivery
      (residual overall p = 0.19). CONCLUSION: The presence of Mycoplasma genitalium in
      the vagina of pregnant women is an independent risk factor for spontaneous
      preterm delivery.

PMID- 16801314
TI  - The first 48 hours: Comparing 12-hour and 24-hour betamethasone dosing when
      preterm deliveries occur rapidly.
AB  - OBJECTIVE: To compare neonatal outcomes when dosing betamethasone every 12 hours
      compared to the standard 24-hour dosing regimen when premature deliveries occur
      within 48 hours of presentation. METHODS: A retrospective chart review was
      performed on preterm deliveries from January 1, 1996 to July 1, 2000. Deliveries
      that occurred less than 48 hours after initiation of antenatal steroids were
      analyzed for neonatal outcomes. RESULTS: Betamethasone was given to 562 women, of
      whom 166 delivered less than 48 hours after beginning therapy. There were no
      statistically significant differences in the rates of respiratory distress
      syndrome, surfactant use, chronic lung disease, intraventricular hemorrhage,
      neonatal death, or other outcomes between the two groups. The only statistically
      significant difference between the two groups was for venous cord blood pH (7.27
      vs. 7.32, p = 0.01). Separating the results into delivery from 0-24 and 24-48
      hour groups, there were no significant differences between the 12-hour and 24
      hour dosing groups, although small sample size limited conclusions. CONCLUSION:
      Dosing betamethasone in 12-hour intervals may result in similar neonatal outcomes
      compared to the standard 24-hour regimen when delivery occurs within 48 hours of
      therapy initiation.

PMID- 16801315
TI  - Rupture of uterine scar 3 weeks after vaginal birth after cesarean section
      (VBAC).
AB  - Uterine scar rupture in vaginal birth after cesarean section (VBAC) usually
      occurs during labor or after placental extraction. We report herein the case of a
      patient who had a cesarean section in her first pregnancy and a VBAC in her
      second. The present one also ended with a normal VBAC and a documented intact
      scar, which then ruptured three weeks later.

PMID- 16801316
TI  - Breast-feeding in a woman with cystic fibrosis undergoing antibiotic intravenous
      treatment.
AB  - We report the case of a 30-year-old woman with cystic fibrosis (CF) chronically
      infected with Pseudomonas aeruginosa who delivered and breast-fed a healthy boy.
      While breast-feeding the woman had to undergo an i.v. antibiotic course with
      tobramycin, due to pulmonary exacerbation. Tobramycin was not detected in her
      milk and lactation could be continued. This is the first time that the presence
      of tobramycin in the milk of a CF woman during i.v. administration has been
      investigated.

PMID- 16801317
TI  - Prenatal diagnosis of a cervical teratoma with a cytogenetic study.
AB  - We describe a cervical teratoma revealed in the prenatal period that was studied
      cytogenetically. We were recently confronted with the case of a fetal solid neck
      mass suggestive of a teratoma. After termination of pregnancy the tumor was
      studied cytogenetically. This is the first case in the recent literature where a
      clone of cells with an additional chromosome marker has been detected.
      Cytogenetic study of the fetal blood in addition to cytogenetic study of the
      tumor after the termination of pregnancy showed the karyotypes 46,XY and
      46,XY/47,XY + m, respectively. Fetal cervical teratoma is a rare condition.
      Genetic investigation in the case should be considered in order to reveal
      chromosome rearrangements.

PMID- 16801318
TI  - Effects of visual environment on quiet standing by young and old adults.
AB  - The authors manipulated the circumstances in which individuals are typically
      embedded when standing upright by manipulating the intensity of light and the
      stationary structure of the environment. They expected that the manipulations
      would affect 12 older participants (aged 65-82 years) more than it would 12
      younger participants (aged 22-24 years). Linear (e.g., total path length) and
      nonlinear (e.g., maximum line length of recurrent points in phase space) measures
      of the center of pressure time series confirmed that expectation. Moreover, for
      some measures, there was a suggestion that participants' visual contrast
      sensitivity (an index of neurophysiological age) was a more important
      contributing factor overall than was their chronological age. In the Discussion,
      the authors highlight the significance of interactive effects of environmental,
      organismic, and task constraints on quiet standing.

PMID- 16801319
TI  - A deficit in older adults' effortful selection of cued responses.
AB  - J. J. Adam et al. (1998) provided evidence for an "age-related deficit in
      preparing 2 fingers on 2 hands, but not on 1 hand" (p. 870). Instead of having an
      anatomical basis, the deficit could result from the effortful processing required
      for individuals to select cued subsets of responses that do not coincide with
      left and right subgroups. The deficit also could involve either the ultimate
      benefit that can be attained or the time required to attain that benefit. The
      authors report 3 experiments (Ns = 40, 48, and 32 participants, respectively) in
      which they tested those distinctions by using an overlapped hand placement
      (participants alternated the index and middle fingers of the hands), a normal
      hand placement, and longer precuing intervals than were used in previous studies.
      The older adults were able to achieve the full precuing benefit shown by younger
      adults but required longer to achieve the maximal benefit for most pairs of
      responses. The deficit did not depend on whether the responses were from
      different hands, suggesting that it lies primarily in the effortful processing
      required for those subsets of cued responses that are not selected easily.

PMID- 16801320
TI  - Simultaneous specification of amplitudes and directions of bimanual reversal
      movements.
AB  - Intermanual interactions are modulated by task requirements in the course of
      motor preparation. In particular, amplitude coupling is strong when identical
      amplitudes are specified concurrently for the 2 hands but relaxed when different
      amplitudes are specified. Similarly, directional coupling is symmetric when
      symmetric directions are specified concurrently but turns to parallel when
      parallel directions are specified. Here, the author investigated whether the
      modulations of amplitude coupling and directional coupling in the course of motor
      preparation are independent or interact. Application of the timed-response
      procedure, which enables one to manipulate the time available for motor
      preparation, in 9 participants revealed a weakly interactive pattern. Directional
      coupling tended to be reduced when different rather than same amplitudes were
      specified concurrently, and amplitude coupling tended to be reduced when parallel
      rather than symmetric directions were specified concurrently. In general,
      interactive effects were also apparent in the rates at which directions and
      amplitudes were specified. Those observations are consistent with the notion that
      intermanual amplitude and direction interference are mediated by different but
      partially overlapping neural structures.

PMID- 16801321
TI  - Dynamics of learning new postural patterns: influence on preexisting spontaneous
      behaviors.
AB  - In stance, rotations around the hips and ankles typically exhibit a relative
      phase close to 20 degrees or 180 degrees . In 2 experiments, the authors studied
      the reciprocal influence of those coordination tendencies with learning an ankle
      hip relative phase of 135 degrees . Before, during, and after learning a new mode
      of coordination, they assessed participants' (N = 24 in each experiment)
      spontaneous postural patterns with a tracking task in which no specific
      coordination was required. Learning the 135 degrees phase relation led to
      persistent modifications of the spontaneous in-phase and antiphase modes.
      Contrary to the theoretical predictions of the dynamical approach, the initial
      stability of the preexisting patterns did not influence the difficulty of
      producing the new mode or the improvement in performance during learning. Initial
      stability did, however, influence the rate and type of modification of
      spontaneous patterns. The authors discuss the results in relation to conclusions
      drawn from bimanual studies.

PMID- 16801322
TI  - The role of segmental mass and moment of inertia in dynamic-contact task
      construction.
AB  - The authors examined whether differences between children and adults in the
      application of muscle forces during a dynamic-contact task (cycling) can be
      attributed to children's relatively lower segmental mass and moment of inertia.
      They examined pedal-force construction as adults and younger and older children
      (n = 7 in each group), with and without mass added to their limbs, pedaled an
      appropriately scaled bicycle ergometer. When mass was added to their limbs,
      children adjusted muscular forces on the pedal in a way that began to approach
      the pattern demonstrated by adults. Because age, neuromotor maturation, and motor
      experience were held constant, it seems plausible that by 6 to 8 years of age,
      and perhaps younger, physical size and growth limit children's production of
      adult-like muscle forces on the pedal.

PMID- 16801324
TI  - Observation of family functioning at mealtime: a comparison between families of
      children with and without overweight.
AB  - OBJECTIVE: To examine differences between families of children with and without
      overweight on parental control and support. METHODS: Twenty-eight families with
      an overweight child and a control group of 28 families with a normal weight child
      (age range 7-13 years) participated in the study. Observations and self-reports
      of mealtime family functioning were administered and analyzed. RESULTS: Parents
      of children with overweight reported to exert more control on their children's
      feeding behavior and an equal amount of parental support in comparison with
      parents of children without overweight. However, observations at mealtime
      indicated that in families with an overweight child, maladaptive control
      strategies were twice as prevalent, and less parental support was displayed.
      CONCLUSIONS: Self-reports and observations provide complementary information on
      how parents interact with their overweight children. Family-based treatment
      programs should include discussions on the adequate amount of parental control
      and support.

PMID- 16801323
TI  - Binge eating in overweight treatment-seeking adolescents.
AB  - OBJECTIVE: To examine the frequency and recency of binge eating in relation to
      psychopathology in overweight, treatment-seeking adolescents. METHODS: We
      investigated psychological correlates of the frequency and recency of reported
      loss of control (LOC) eating episodes in 160 overweight (body mass index [BMI]:
      40.7 +/- 8.8 kg/m(2)) adolescents. On the basis of the responses to the eating
      disorder examination (EDE), participants were categorized into one of four
      groups: full-syndrome binge eating disorder (BED); recent but infrequent binge
      eating (episodes within the 3 months before interview; RECENT-BINGE); remote and
      infrequent LOC eating (episodes occurring >3 months before assessment; PAST-LOC),
      or no history of LOC episodes (NE). RESULTS: The BED group reported higher EDE
      scores (global, p < .01), and more negative mood and anxiety than all other
      groups (p's < .01). Compared with NE, RECENT-BINGE also reported more anxiety and
      higher EDE scores (p's < .01). CONCLUSIONS: Overweight, treatment-seeking
      adolescents with BED are clearly distinguishable from teens without the disorder
      on measures of eating-related psychopathology, mood, and anxiety. RECENT-BINGE,
      but not PAST-LOC, is also associated with significantly greater eating-related
      and general psychopathology.

PMID- 16801325
TI  - The influences of demographics and individual differences on children's selection
      of risky pedestrian routes.
AB  - OBJECTIVE: Thousands of American children under the age of 10 are injured
      annually as pedestrians. Despite the scope of this public health problem,
      knowledge about behavioral factors involved in the etiology of child pedestrian
      injury remains sparse. The present study considered the roles of age, gender,
      ethnicity, family income, and inhibitory control on children's selection of safe
      pedestrian routes. METHODS: Children's selections of risky pedestrian routes were
      examined in two laboratory analogue tasks. Multiple behavioral and self-report
      methods were used to measure temperamental inhibitory control. RESULTS: Children
      from lower-income families, children of ethnic minority background, younger
      children, and those with less temperamental control selected riskier pedestrian
      routes. CONCLUSIONS: Prevention efforts might be tailored to focus on children at
      higher risk for pedestrian injury, such as younger, under-controlled children.

PMID- 16801326
TI  - Alcohol relaxes the stiff heart.

PMID- 16801327
TI  - Prasugrel, clopidogrel, and combining Swedish apples with American oranges.

PMID- 16801328
TI  - Transgenic mice expressing the myotilin T57I mutation unite the pathology
      associated with LGMD1A and MFM.
AB  - Myotilin is a muscle-specific Z-disc protein with putative roles in myofibril
      assembly and structural upkeep of the sarcomere. Several myotilin point mutations
      have been described in patients with limb-girdle muscular dystrophy type 1A
      (LGMD1A), myofibrillar myopathy (MFM), spheroid body myopathy (SBM), three
      similar adult-onset, progressive and autosomal dominant muscular dystrophies. To
      further investigate myotilin's role in the pathogenesis of these muscle diseases,
      we have characterized three independent lines of transgenic mice expressing
      mutant (T57I) myotilin under the control of the human skeletal actin promoter.
      Similar to LGMD1A and MFM patients, these mice develop progressive myofibrillar
      pathology that includes Z-disc streaming, excess myofibrillar vacuolization and
      plaque-like myofibrillar aggregation. These aggregates become progressively
      larger and more numerous with age. We show that the mutant myotilin protein
      properly localizes to the Z-disc and also heavily populates the aggregates, along
      with several other Z-disc associated proteins. Whole muscle physiological
      analysis reveals that the extensor digitorum longus muscle of transgenic mice
      exhibits significantly reduced maximum specific isometric force compared with
      littermate controls. Intriguingly, the soleus and diaphragm muscles are spared of
      any abnormal myopathology and show no reductions in maximum specific force. These
      data provide evidence that myotilin mutations promote aggregate-dependent
      contractile dysfunction. In sum, we have established a promising patho
      physiological mouse model that unifies the phenotypes of LGMD1A, MFM and SBM.

PMID- 16801329
TI  - Severe pancreas hypoplasia and multicystic renal dysplasia in two human fetuses
      carrying novel HNF1beta/MODY5 mutations.
AB  - Heterozygous mutations in the HNF1beta/vHNF1/TCF2 gene cause maturity-onset
      diabetes of the young (MODY5), associated with severe renal disease and abnormal
      genital tract. Here, we characterize two fetuses, a 27-week male and a 31.5-week
      female, carrying novel mutations in exons 2 and 7 of HNF1beta, respectively.
      Although these mutations were predicted to have different functional
      consequences, both fetuses displayed highly similar phenotypes. They presented
      one of the most severe phenotypes described in HNF1beta carriers: bilateral
      enlarged polycystic kidneys, severe pancreas hypoplasia and abnormal genital
      tract. Consistent with this, we detected high levels of HNF1beta transcripts in 8
      week human embryos in the mesonephros and metanephric kidney and in the
      epithelium of pancreas. Renal histology and immunohistochemistry analyses of
      mutant fetuses revealed cysts derived from all nephron segments with multilayered
      epithelia and dysplastic regions, accompanied by a marked increase in the
      expression of beta-catenin and E-cadherin. A significant proportion of cysts
      still expressed the cystic renal disease proteins, polycystin-1, polycystin-2,
      fibrocystin and uromodulin, implying that cyst formation may result from a
      deregulation of cell-cell adhesion and/or the Wnt/beta-catenin signaling pathway.
      Both fetuses exhibited a severe pancreatic hypoplasia with underdeveloped and
      disorganized acini, together with an absence of ventral pancreatic-derived
      tissue. beta-catenin and E-cadherin were strongly downregulated in the exocrine
      and endocrine compartments, and the islets lacked the transporter essential for
      glucose-sensing GLUT2, indicating a beta-cell maturation defect. This study
      provides evidence of differential gene-dosage requirements for HNF1beta in normal
      human kidney and pancreas differentiation and increases our understanding of the
      etiology of MODY5 disorder.

PMID- 16801330
TI  - Successful treatment using tacrolimus (FK506) in a patient with TNF receptor
      associated periodic syndrome (TRAPS) complicated by monocytic fasciitis.

PMID- 16801331
TI  - Association of mannose-binding lectin gene polymorphisms with antiphospholipid
      syndrome, cardiovascular disease and chronic damage in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To investigate the association of mannose-binding lectin (MBL)
      deficient genotypes with cardiovascular disease in a large series of patients
      with systemic lupus erythematosus (SLE). METHODS: A total of 114 patients
      diagnosed with SLE were included in the study. MBL polymorphisms were
      investigated by sequencing-based DNA typing of the promoter and exon 1 of the
      MBL2 gene. The genotypes 0/0, 0/XA and XA/XA were considered as MBL-low
      genotypes. RESULTS: A higher prevalence of cardiovascular disease was observed in
      patients carrying MBL-low genotypes compared with those carrying MBL-high
      genotypes [30 vs 9%, P = 0.012, odds ratio (OR) 4.54, 95% confidence interval
      (CI) 1.20-16.46]. Patients with MBL-low genotypes also presented higher mean
      values for total cholesterol (228.6 vs 202.3 mg/dl, P = 0.017) and low-density
      lipoprotein (LDL) cholesterol (139.9 vs 121.9 mg/dl, P = 0.045), a higher
      frequency of chronic renal failure (30 vs 4%, P = 0.001), vasculitis (30 vs 11%,
      P = 0.043), heart valve lesions (71 vs 32%, P = 0.026), cardiac valve dysfunction
      (57 vs 7%, P = 0.0004) and associated APS (39 vs 12%, P = 0.005), a higher mean
      Systemic Lupus International Collaborating Clinics score (2.09 vs 1.26, P =
      0.029) and a lower prevalence of low C4 levels (43 vs 71%, P = 0.015).
      Multivariate analysis of genetic, clinical and immunological variables showed
      that only antiphospholipid syndrome (APS) was independently associated with
      cardiovascular events (P = 0.001). CONCLUSION: Although the prevalence of
      cardiovascular disease in our SLE patients carrying MBL-deficient genotypes was
      3.3 times higher than in patients with non-deficient genotypes, only APS was
      independently associated with cardiovascular events. This suggests that the
      higher frequency of thrombotic events in SLE patients carrying MBL-deficient
      genotypes might be related to coexisting APS.

PMID- 16801332
TI  - A dermatotoxicokinetic model of human exposures to jet fuel.
AB  - Workers, both in the military and the commercial airline industry, are exposed to
      jet fuel by inhalation and dermal contact. We present a dermatotoxicokinetic
      (DTK) model that quantifies the absorption, distribution, and elimination of
      aromatic and aliphatic components of jet fuel following dermal exposures in
      humans. Kinetic data were obtained from 10 healthy volunteers following a single
      dose of JP-8 to the forearm over a surface area of 20 cm2. Blood samples were
      taken before exposure (t = 0 h), after exposure (t = 0.5 h), and every 0.5 h for
      up to 3.5 h postexposure. The DTK model that best fit the data included five
      compartments: (1) surface, (2) stratum corneum (SC), (3) viable epidermis, (4)
      blood, and (5) storage. The DTK model was used to predict blood concentrations of
      the components of JP-8 based on dermal-exposure measurements made in occupational
      exposure settings in order to better understand the toxicokinetic behavior of
      these compounds. Monte Carlo simulations of dermal exposure and cumulative
      internal dose demonstrated no overlap among the low-, medium-, and high-exposure
      groups. The DTK model provides a quantitative understanding of the relationship
      between the mass of JP-8 components in the SC and the concentrations of each
      component in the systemic circulation. The model may be used for the development
      of a toxicokinetic modeling strategy for multiroute exposure to jet fuel.

PMID- 16801333
TI  - Factors that influence cancer patients' anxiety following a medical consultation:
      impact of a communication skills training programme for physicians.
AB  - BACKGROUND: No study has yet assessed the impact of physicians' skills
      acquisition after a communication skills training programme on the evolution of
      patients' anxiety following a medical consultation. This study aimed to compare
      the impact, on patients' anxiety, of a basic communication skills training
      programme (BT) and the same programme consolidated by consolidation workshops
      (CW), and to investigate physicians' communication variables associated with
      patients' anxiety. PATIENTS AND METHODS: Physicians, after attending the BT, were
      randomly assigned to CW or to a waiting list. The control group was not a non
      intervention group. Consultations with a cancer patient were recorded. Patients'
      anxiety was assessed with the State Trait Anxiety Inventory before and after a
      consultation. Communication skills were analysed according to the Cancer Research
      Campaign Workshop Evaluation Manual. RESULTS: No statistically significant change
      over time and between groups was observed. Mixed-effects modelling showed that a
      decrease in patients' anxiety was linked with screening questions (P = 0.045),
      physicians' satisfaction about support given (P = 0.004) and with patients'
      distress (P < 0.001). An increase in anxiety was linked with breaking bad news (P
      = 0.050) and with supportive skills (P = 0.013). No impact of the training
      programme was observed. CONCLUSIONS: This study shows the influence of some
      communication skills on the evolution of patients' anxiety. Physicians should be
      aware of these influences.

PMID- 16801334
TI  - Rationale for the use of somatostatin analogs as antitumor agents.
AB  - BACKGROUND: There is a need for novel antitumor agents that demonstrate efficacy
      in currently refractory tumors without adding to the toxicity of therapy. The
      somatostatin analogs, which have demonstrated antineoplastic activities in
      experimental tumor models, and good tolerability and safety profiles are
      attractive candidates. MATERIALS AND METHODS: Data from preclinical studies
      provide evidence for direct and indirect mechanisms by which somatostatin analogs
      exert antitumor effects. RESULTS: Direct antitumor activities, mediated through
      somatostatin receptors (sst(1)-sst(5)) expressed in tumor cells, include blockade
      of autocrine/paracrine growth-promoting hormone and growth factor production,
      inhibition of growth factor-mediated mitogenic signals and induction of
      apoptosis. Indirect antitumor effects include inhibition of growth-promoting
      hormone and growth factor secretion, and antiangiogenic actions. Many human
      tumors express more than one somatostatin receptor subtype, with sst(2) being
      predominant. Somatostatin analogs such as octreotide and lanreotide, which
      present a high affinity for sst(2), are in current clinical use to alleviate
      symptoms in patients with endocrine tumors, and radiolabeled somatostatin analogs
      have been developed for diagnosis and radiotherapy. CONCLUSIONS: While the
      rationale exists for the use of somatostatin analogs as antitumor agents, studies
      are ongoing to identify analogs with activity across the range of receptor
      subtypes to maximize the potential of such treatment.

PMID- 16801335
TI  - The rising burden of cancer in the developing world.
AB  - Cancer remains one of the leading causes of morbidity and mortality worldwide. It
      is predicted that by 2020, the number of new cases of cancer in the world will
      increase to more than 15 million, with deaths increasing to 12 million. Much of
      the burden of cancer incidence, morbidity, and mortality will occur in the
      developing world. This forms part of a larger epidemiological transition in which
      the burden of chronic, non-communicable disease-once limited to industrialized
      nations-is now increasing in less developed countries. In addition to the
      accumulating risks associated with diet, tobacco, alcohol, lack of exercise, and
      industrial exposures, the developing world is already burdened by cancers some of
      which are attributable to infectious diseases. These disparities in cancer risk
      combined with poor access to epidemiological data, research, treatment, and
      cancer control and prevention combine to result in significantly poorer survival
      rates in developing countries for a range of specific malignancies. This paper
      summarizes the recent trends in the epidemiology and survival of cancers in the
      developing and developed world, and explores potential causes and policy
      responses to the disproportionate and growing cancer burden in less developed
      countries. Such responses may include raising awareness as well as education and
      training to foster better informed decision-making, together with improved cancer
      surveillance, early detection and emphasis on prevention. Improved health care
      financing and international initiatives and/or partnerships could also provide
      additional impetus in targeting resources where needed urgently.

PMID- 16801336
TI  - Cancer initiatives in developing countries.
AB  - The coming decades will bring dramatic increases in morbidity and mortality from
      cancer in the developing world. The burden of cancer is increasing globally, with
      an expected 20 million new cases per year in 2020, half of which will be in low-
      and middle-income countries. Despite an already overwhelming burden of health
      problems, developing countries must somehow address this cancer pandemic and
      their alarming share of cancer illness. Many large-scale and innovative worldwide
      initiatives have been launched in the fight against cancer. These programs
      represent colossal efforts to expand resources for health education among people
      and healthcare workers in developing countries and to increase awareness of
      cancer prevention. Many novel evidence-based and culturally-relevant programs are
      being implemented for screening and early prevention of common cancers. Several
      key initiatives are supporting clinical research, guideline development, oncology
      training, and appropriate technology transfer, such as access to electronic
      medical literature. Treatment programs are expanding access and quality of
      radiologic and pharmacologic therapies for cancer. These initiatives represent an
      unprecedented level of and cooperation among international agencies, governmental
      and nongovernmental organizations, international foundations, scientific
      societies, local institutions, and industry. This review examines the scope of
      need in response to the increasing burden of cancer in the developing world and
      major initiatives that have been created to respond to these needs.

PMID- 16801337
TI  - Cancer initiatives in Sudan.
AB  - The broad ethnic and climatic diversity of Sudan makes it in many ways a
      microcosm of Africa. Sudan is experiencing a burgeoning cancer epidemic that
      carries many challenges that are characteristic of developing countries. These
      include a high incidence of advanced, difficult-to-treat disease at presentation,
      and a high cancer burden that is related to infectious diseases. To address this
      problem, Sudan has instituted a comprehensive national cancer control programme
      which is focused on prevention, early detection, improved treatment and
      palliative care. This programme focuses on three common cancers for which
      effective prevention, screening and treatments are available; breast, cervical
      and oral cancer. This article describes some preventive approaches through public
      awareness campaigns and education of medical professionals, and screening
      programmes that are being instituted in Sudan. Sudan provides an example of how
      the implementation of a comprehensive and carefully planned national cancer
      control programme in a very low-resource setting can improve the lives of cancer
      patients.

PMID- 16801338
TI  - Cancer diagnosis and telemedicine: a case study from Cambodia.
AB  - Cambodia is one of the least developed countries in the world, and presents major
      challenges to the provision of effective healthcare. Partners Telemedicine, a non
      profit organization based in Boston, MA, is leading a pilot project to assess
      whether accurate diagnosis and treatment can be provided by email to patients in
      remote locales in the developing world. This project, in rural Cambodia, has had
      a beneficial impact on the public health of the communities served. There has
      been a reduced demand for acute care services, with patients seeking treatment
      earlier and adhering better to their prescribed treatment regimens for chronic
      diseases, and the project illustrates the potential for simple communications
      technology to improve care, even to some of the most impoverished communities.
      However, infrastructure must be improved in Cambodia to enable patients, in
      particular cancer patients, to receive acute care that can only be provided in
      distant Phnom Penh.

PMID- 16801340
TI  - Perceptions of cancer in developing countries.

PMID- 16801339
TI  - Ongoing challenges of a global international patient assistance program.
AB  - The Glivec International Patient Assistance Program (GIPAP) that is supported by
      Novartis Oncology provides Glivec (imatinib), an innovative oral therapy for
      chronic myelogenous leukemia and gastrointestinal stromal tumours, at no cost to
      patients in developing countries who could otherwise not afford treatment. Using
      a novel direct-to-patient approach this program is currently successfully
      providing Glivec to underserved patients in 81 countries. A number of challenges
      were faced in the implementation of this program in countries where cancer is not
      a priority, and where the healthcare and other infrastructure can be very
      limited. By working within the existing healthcare system of each country, and
      with any national cancer control programme that may be in place, through careful
      selection of qualified institutions and physicians, while maintaining a global
      approach to ensure consistency and quality, GIPAP has become an efficient and
      sustainable access program. Novartis has made a long-term commitment to GIPAP,
      and is currently exploring new patient access programs for other drugs.

PMID- 16801341
TI  - Cancer in developing countries: challenges and solutions.

PMID- 16801342
TI  - World Health Organization cancer priorities in developing countries.
AB  - The burden of cancer in developing countries is growing and threatens to exact a
      heavy morbidity, mortality, and economic cost in these countries in the next 20
      years. The unfolding global public health dimensions of the cancer pandemic
      demand a widespread effective international response. The good news is that the
      majority of cancers in developing countries are preventable, and the efficacy of
      treatment can be improved with early detection. Currently, the knowledge exists
      to implement sound, evidence-based practices in cancer prevention,
      screening/early detection, treatment, and palliation. It is estimated that the
      information at hand could prevent up to one-third of new cancers and increase
      survival for another one-third of cancers detected at an early stage. To achieve
      this, knowledge must be translated into action. To facilitate the call to action
      in the fight against cancer, the World Health Organization (WHO) has developed a
      comprehensive approach to cancer control. The WHO has produced many valuable
      guidelines and resources for the effective implementation of national cancer
      control programs. Several milestones in the WHO's efforts include the Framework
      Convention for Tobacco Control, and global strategies for diet and exercise,
      reproductive health, and cervical cancer. This review examines the strategies and
      approaches that have successfully resulted into global action to confront the
      rising global burden of cancer in the developing world.

PMID- 16801343
TI  - Hospitals' responses to nurse staffing shortages.
AB  - Hospitals have used a mix of short-term and long-term strategies to deal with
      nurse shortages, particularly efforts emphasizing nurse education, competitive
      compensation, and temporary staff. Interviews with health care leaders from Round
      Five of the Community Tracking Study indicate that these activities, in
      conjunction with other factors, have assisted in reducing shortages of hospital
      nurses. However, hospitals' actions have increased costs and raised concerns
      about their potential impact on patient care. Additionally, a large degree of
      doubt exists among hospitals about their ability to meet future nursing needs.

PMID- 16801344
TI  - Polyalanine and polyserine frameshift products in Huntington's disease.
AB  - Codon reiteration disorders are caused by abnormal expansions of either
      polyglutamine or polyalanine tracts within the coding region of a protein. These
      mutations impair normal protein folding, resulting in aggregate formation in the
      affected tissues. Huntington's disease is the most common of the nine disorders
      caused by polyglutamine expansion mutations. The most extensively studied
      polyalanine expansion disorder is oculopharyngeal muscular dystrophy. There may
      be a link between diseases caused by polyglutamine and polyalanine expansion
      mutations as it has been shown that the expanded CAG/polyglutamine tract within
      the SCA3 gene can shift to the GCA[corrected]/polyalanine frame. Here, we show
      that this frameshifting phenomenon is more widespread and occurs in Huntington's
      disease. We have shown both +1 frameshift and +2 frameshift products (which may
      contain polyalanine or polyserine tracts, respectively) in human postmortem
      Huntington's disease brains and in a transgenic mouse model of Huntington's
      disease. Our data suggest that +1 and +2 frameshift products are generated at low
      levels. This may be relevant to the pathogenesis of human Huntington's disease,
      as we have previously shown that both polyserine and polyalanine-containing
      proteins are modifiers of mutant huntingtin toxicity, with low expression levels
      of polyalanine-containing proteins having a protective effect.

PMID- 16801345
TI  - A molecular and clinical study of Larsen syndrome caused by mutations in FLNB.
AB  - BACKGROUND: Larsen syndrome is an autosomal dominant osteochondrodysplasia
      characterised by large-joint dislocations and craniofacial anomalies. Recently,
      Larsen syndrome was shown to be caused by missense mutations or small inframe
      deletions in FLNB, encoding the cytoskeletal protein filamin B. To further
      delineate the molecular causes of Larsen syndrome, 20 probands with Larsen
      syndrome together with their affected relatives were evaluated for mutations in
      FLNB and their phenotypes studied. METHODS: Probands were screened for mutations
      in FLNB using a combination of denaturing high-performance liquid chromatography,
      direct sequencing and restriction endonuclease digestion. Clinical and
      radiographical features of the patients were evaluated. RESULTS AND DISCUSSION:
      The clinical signs most frequently associated with a FLNB mutation are the
      presence of supernumerary carpal and tarsal bones and short, broad, spatulate
      distal phalanges, particularly of the thumb. All individuals with Larsen syndrome
      associated FLNB mutations are heterozygous for either missense or small inframe
      deletions. Three mutations are recurrent, with one mutation, 5071G-->A, observed
      in 6 of 20 subjects. The distribution of mutations within the FLNB gene is non
      random, with clusters of mutations leading to substitutions in the actin-binding
      domain and filamin repeats 13-17 being the most common cause of Larsen syndrome.
      These findings collectively define autosomal dominant Larsen syndrome and
      demonstrate clustering of causative mutations in FLNB.

PMID- 16801346
TI  - CDH1/E-cadherin germline mutations in early-onset gastric cancer.
AB  - BACKGROUND: Gastric cancer remains a leading cause of cancer deaths worldwide.
      Genetic factors, including germline mutations in E-cadherin (CDH1, MIM#192090) in
      hereditary diffuse gastric cancer (HDGC, MIM#137215), are implicated in this
      disease. Family studies have reported CDH1 germline mutations in HDGC but the
      role of CDH1 germline mutations in the general population remains unclear. AIMS:
      To examine the frequency of CDH1 germline mutations in a population-based series
      of early-onset gastric cancer (EOGC <50 years old). METHODS: 211 cases of EOGC
      were identified in Central-East Ontario region from 1989 to 1993, with archival
      material and histological confirmation of non-intestinal type gastric cancer
      available for 81 subjects. Eligible cases were analysed for CDH1 germline
      mutations by single-strand conformation polymorphism, variants were sequenced,
      and tumours from cases with functional mutations were stained for E-cadherin
      (HECD-1) using immunohistochemistry. RESULTS: 1155 (89%) of 1296 polymerase chain
      reactions amplified successfully. One new germline deletion (nt41delT) was
      identified in a 30-year-old patient with isolated cell gastric cancer. The
      overall frequency of germline CDH1 mutations was 1.3% (1/81) for EOGC and 2.8%
      (1/36) for early-onset isolated cell gastric cancer. CONCLUSION: This is the
      first population-based study, in a low-incidence region, of genetic
      predisposition to gastric cancer. Combined with our previous report of germline
      hMLH1 mutations in two other subjects from this series, it is suggested that 2-3%
      of EOCG cases in North Americans may be owing to high-risk genetic mutations.
      These data should inform cancer geneticists on the utility of searching for
      specific genetic mutations in EOGC.

PMID- 16801347
TI  - AMP-kinase alpha2 subunit gene PRKAA2 variants are associated with total
      cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein
      cholesterol in normal women.
AB  - BACKGROUND: 5'-AMP-activated protein kinase (AMPK) inactivates critial ensymes in
      fatty acid and cholesterol synthesis. We hypothesised that the serum lipid
      profile may be influenced by genetic variation in the AMPK catalytic alpha2
      subunit. METHOD: We examined association of 5 tagging SNPs (tSNPs) in the PRKAA2
      gene with serum lipids in 2777 normal Caucasian females (mean age 47.4+/-12.5
      years). RESULTS: All tSNPs were associated with total- and LDL-cholesterol,
      (p<0.001 to 0.034), explaining variances of 0.13-0.59% and 0.11-0.55%
      respectively. One haplotype (frequency 34.7%) showed lower total- and LDL
      cholesterol compared with the most common haplotype (frequency 45.7%) (p< or
      =0.001), explaining 0.78% of total- and 0.75% of LDL-cholesterol. Another
      haplotype (frequency 10.5%) was significantly associated with lower HDL
      cholesterol (p = 0.005), explaining 0.59% of variance. CONCLUSIONS: PRKAA2 gene
      variants are significantly associated with serum lipoproteins in a large sample
      of normal female Caucasians.

PMID- 16801349
TI  - Protein kinase Cgamma autoimmunity in paraneoplastic cerebellar degeneration and
      non-small-cell lung cancer.
AB  - BACKGROUND: The clinical and immunological profiles of patients with
      paraneoplastic cerebellar degeneration (PCD) and non-small-cell lung cancer
      (NSCLC) are not well known. OBJECTIVE: To review the clinical and immunological
      features of patients with PCD, NSCLC and without well-characterised onconeural
      antibodies. METHODS: The clinical features of nine patients with the diagnosis of
      classical PCD and NSCLC, included in our archives, were retrospectively reviewed.
      The presence of antibodies to cerebellar components was determined by
      immunohistochemistry and immunoblot of rat cerebellum. A cDNA library of human
      cerebellum was screened with the positive sera to identify the antigen. RESULTS:
      Nine patients with PCD and NSCLC were identified. Six patients were men, and the
      median age at diagnosis of PCD was 63 (range 47-73) years. PCD was completely
      reversed in two patients, and partially in one, after treatment of the tumour.
      The serum of one of the patients with PCD showed a unique reactivity with
      Purkinje cells. The screening of a cerebellar-expression library resulted in the
      isolation of protein kinase Cgamma (PKCgamma). PKCgamma immunoreactivity was not
      observed in the serum of 170 patients with non-paraneoplastic neurological
      syndromes, 27 patients with PCD, no onconeural antibodies and small-cell lung
      cancer, and 52 patients with NSCLC without paraneoplastic neurological syndromes.
      The NSCLC from 11 patients without PCD did not express PKCgamma at either the RNA
      or protein level. However, many cells of the NSCLC of the patient with PKCgamma
      antibodies expressed PKCgamma. CONCLUSION: PCD occurs in patients with NSCLC
      without typical onconeural antibodies and is associated with immune reactions
      against key proteins of the Purkinje cells.

PMID- 16801350
TI  - Antipsychotics and cognitive decline in Alzheimer's disease: the LASER
      Alzheimer's disease longitudinal study.
AB  - OBJECTIVE: To investigate in a longitudinal cohort of people with Alzheimer's
      disease whether taking antipsychotics is associated with more rapid cognitive
      deterioration. METHOD: From a sample of 224 people with Alzheimer's disease
      recruited as epidemiologically representative, those taking antipsychotic drugs
      for more than 6 months were compared with those who were not, in terms of change
      in three measures of cognition. The effects of potential mediators and
      confounders (demographic factors, neuropsychiatric symptoms, cognitive severity
      and cholinesterase inhibitors) were also examined. RESULTS: No significant
      difference was observed in cognitive decline between those taking antipsychotics
      (atypical or any) and others on any measure of cognition. The only predictor of
      more cognitive decline was greater baseline cognitive severity (B = 3.3, 95%
      confidence interval 0.6 to 6.1, t = 2.4, p<0.05). Although mortality was higher
      in those treated with antipsychotics, this reflected their greater age and
      severity of dementia. The results were the same when the whole cohort was
      included rather than the select group with potential to change who had been
      taking antipsychotics continuously. CONCLUSIONS: In this, the first cohort study
      investigating the effects of atypical antipsychotics on cognitive outcome in
      Alzheimer's disease, those taking antipsychotics were no more likely to decline
      cognitively over 6 months. Although clinicians should remain cautious when
      prescribing antipsychotic drugs to people with Alzheimer's disease, any increase
      in cognitive deterioration is not of the magnitude previously reported. There is
      a need for cohort studies that follow up patients from first prescription in
      clinical practice for a period of months rather than weeks to determine "real
      life" risks and benefits.

PMID- 16801351
TI  - Attentional deficits affect activities of daily living in dementia-associated
      with Parkinson's disease.
AB  - OBJECTIVE: To investigate the effects of attentional deficits on activities of
      daily living (ADL) in patients with dementia associated with Parkinson's disease
      (PDD). METHOD: 461 patients were assessed neuropsychologically. Factor analyses
      were used to differentiate attention from other cognitive functions and to
      differentiate different aspects of ADL functions. The effects of the attentional
      measure on ADL were examined using sequential multiple regression, controlling
      for age, sex, education, severity of motor symptoms and other cognitive
      functions. RESULTS: Three cognitive factors were identified, with one factor
      emerging as a measure of vigilance and focused attention. This factor predicted
      different aspects of ADL status even after controlling for motor functions and
      other cognitive factors. The attention factor was the single strongest cognitive
      predictor of ADL status, matching the strength of the effects of motor functions
      on ADL status. CONCLUSION: Impaired attention is an important determinant of ADL
      functions in patients with PDD.

PMID- 16801352
TI  - Structural anatomy of pure and hemianopic alexia.
AB  - BACKGROUND: The two most common types of acquired reading disorder resulting from
      damage to the territory of the dominant posterior cerebral artery are hemianopic
      and pure alexia. Patients with pronounced hemianopic alexia have a right
      homonymous hemianopia that encroaches into central or parafoveal vision; they
      read individual words well, but generate inefficient reading saccades when
      reading along a line of text. Patients with pure alexia also often have a
      hemianopia but are more disabled, making frequent errors on individual words;
      they have sustained damage to a brain region that supports efficient word
      identification. OBJECTIVE: To investigate the differences in lesion site between
      hemianopic alexia and pure alexia groups, as rehabilitative techniques differ
      between the two conditions. METHODS: High-resolution magnetic resonance images
      were obtained from seven patients with hemianopic alexia and from six patients
      with pure alexia caused by a left occipital stroke. The boundary of each lesion
      was defined and lesion volumes were then transformed into a standard stereotactic
      space so that regional comparisons could be made. RESULTS: The two patient groups
      did not differ in terms of damage to the medial left occipital lobe, but those
      with pure alexia had additional lateral damage to the posterior fusiform gyrus
      and adjacent tissue. CONCLUSIONS: Clinicians will be able to predict the type of
      reading disorder patients with left occipital lesions have from simple tests of
      reading speed and the distribution of damage to the left occipital lobe on brain
      imaging. This information will aid management decisions, including
      recommendations for reading rehabilitation.

PMID- 16801353
TI  - Which electroencephalography (EEG) for epilepsy? The relative usefulness of
      different EEG protocols in patients with possible epilepsy.
AB  - BACKGROUND AND AIMS: Electroencephalography (EEG) is an essential investigative
      tool for use in young people with epilepsy. This study assesses the effects of
      different EEG protocols on the yield of EEG abnormalities in young people with
      possible new epilepsy. METHODS: 85 patients presenting to the unit underwent
      three EEGs with differing protocols: routine EEG (r-EEG), sleep-deprived EEG (SD
      EEG), EEG carried out during drug-induced sleep (DI-EEG). The yield of EEG
      abnormalities was compared using each EEG protocol. RESULTS: 98 patients were
      recruited to the study. Of the 85 patients who completed the study, 33 (39%)
      showed no discernible abnormality on any of their EEG recordings. 36 patients
      (43%) showed generalised spike and wave during at least one EEG recording,
      whereas 15 (18%) had a focal discharge evident at some stage. SD-EEG had a
      sensitivity of 92% among these patients, whereas the sensitivity of DI-EEG and r
      EEG was 58% and 44%, respectively. The difference between the yield from SD-EEG
      was significantly higher than that from other protocols (p < 0.001). Among the 15
      patients showing focal discharges, SD-EEG provoked abnormalities in 11 (73%). r
      EEG and DI-EEG each produced abnormalities in 40% and 27%, respectively. 7
      patients (47%) had changes seen only after sleep deprivation. In 2 (13%), the
      only abnormalities were seen on r-EEG. In only 1 patient with focal discharges
      (7%) was the focal change noted solely after drug-induced sleep. These
      differences did not reach significance. CONCLUSION: EEG has an important role in
      the classification of epilepsies. SD-EEG is an easy and inexpensive way of
      increasing the yield of EEG abnormalities. Using this as the preferred protocol
      may help reduce the numbers of EEGs carried out in young patients presenting with
      epilepsy.

PMID- 16801354
TI  - Time-to-event analyses for long-term treatments--the APPROVe trial.

PMID- 16801355
TI  - Adverse cardiovascular effects of rofecoxib.

PMID- 16801356
TI  - Circles of research.

PMID- 16801357
TI  - Psychometric properties of the Post-Fall Index.
AB  - Evaluation and prevention of falls begin with a thorough understanding of their
      occurrence. Post-fall assessment (PFA) tools should be available to sufficiently
      guide nursing staff in identification of all possible causes. Absence of
      empirically tested PFA tools led to the development of the Post-Fall Index (PFI).
      Developed and validated in three phases, a 76-item PFI was first tested for
      content validity by national experts. Next, it was tested for feasibility with
      registered nurses practicing in nursing homes. Last, it was piloted with a sample
      of 30 falls by older residents of a skilled nursing unit in a continuing care
      retirement community. Review of data from these 30 falls provided the item
      analysis. Reflective of evidenced-based guidelines, a 30-item PFI emerged,
      containing essential items causing falls. Although lengthier than incident
      reports, its comprehensiveness was deemed of higher value. Large absolute
      agreement of items (70%-100%) indicates good interrater reliability. The PFI is
      valid, reliable, and feasible and has clinical utility for the secondary
      prevention of falls.

PMID- 16801358
TI  - HIV/AIDS peer counselors' perspectives on intervention delivery formats.
AB  - This research sought to elicit HIV/AIDS peer counselors' perspectives about
      delivery formats for a counseling intervention. Peer counselors identified
      personal contact as the major advantage of the face-to-face format. Personal
      contact afforded counselors better opportunities to understand and assess
      clients' physical, emotional, and environmental status and allowed them to
      connect with peers in more concrete and personal ways. Being physically present
      was also a very direct and effective way to role model for other HIV-positive
      women. Peer counselors identified a number of inherent barriers and challenges to
      telephone interventions but also recognized potential logistic and personal
      advantages. Despite the overwhelming preference for the face-to-face intervention
      format, counselors acknowledged the potential for conducting successful peer
      counseling over the telephone. A significant finding was that the value and
      meaning of HIV/AIDS peer counselors' work transcended the limitations of either
      delivery format.

PMID- 16801359
TI  - Hand dermatitis risk factors among clinical nurses in Japan.
AB  - The purpose of this study was to establish hand dermatitis (HD) risk factors
      among Japanese nurses. A questionnaire was administered to 1,162 clinical nurses,
      from whom 860 replies were received (response rate of 74.0%). Their overall HD
      prevalence was 53.3%. Several risk factors were identified: using latex gloves
      (odds ratio [OR] 1.9), allergies in adulthood (OR 2.7), urticaria as an adult (OR
      1.5), atopic dermatitis as an adult (OR 2.7), any allergies to latex products (OR
      5.2), skin irritation following contact with latex (OR 4.1), contact dermatitis
      following contact with latex (OR 3.5), family history of hay fever (OR 1.6), and
      family history of atopic dermatitis (OR 1.9). The use of hand cream was
      associated with a 50% reduction in HD risk (OR 0.5). In this study, we found that
      Japanese clinical nurses suffer a significant occupational burden from HD. As
      such, it is essential that hospital managers consider interventions to reduce
      this troublesome occupational disease among clinical nurses in Japan, as
      elsewhere.

PMID- 16801360
TI  - The construction of hepatitis C as a chronic illness.
AB  - The purpose of the article is to present one aspect of the findings of a
      descriptive, exploratory investigation of the self-care decision making of 33
      adults diagnosed with chronic hepatitis C (Hep C), specifically how they
      experienced living with this disease as a chronic illness. The findings were
      interpreted from a social constructivist perspective in which Hep C was viewed as
      both a biomedical entity and a social construction. The authors will suggest that
      although Hep C is constructed by people with the disease as a chronic illness,
      the care of this disease is often based on an acute model that acknowledges its
      chronicity only in terms of the persistence of the virus. The article points to
      the need for a model of Hep C care that incorporates the dimensions of the
      chronic illness experience.

PMID- 16801361
TI  - Novel differential neuroproteomics analysis of traumatic brain injury in rats.
AB  - Approximately two million traumatic brain injury (TBI) incidents occur annually
      in the United States, yet there are no specific therapeutic treatments. The
      absence of brain injury diagnostic endpoints was identified as a significant
      roadblock to TBI therapeutic development. To this end, our laboratory has studied
      mechanisms of cellular injury for biomarker discovery and possible therapeutic
      strategies. In this study, pooled naive and injured cortical samples (48 h
      postinjury; rat controlled cortical impact model) were processed and analyzed
      using a differential neuroproteomics platform. Protein separation was performed
      using combined cation/anion exchange chromatography-PAGE. Differential proteins
      were then trypsinized and analyzed with reversed-phase LC-MSMS for protein
      identification and quantitative confirmation. The results included 59
      differential protein components of which 21 decreased and 38 increased in
      abundance after TBI. Proteins with decreased abundance included collapsin
      response mediator protein 2 (CRMP-2), glyceraldehyde-3-phosphate dehydrogenase,
      microtubule-associated proteins MAP2A/2B, and hexokinase. Conversely C-reactive
      protein, transferrin, and breakdown products of CRMP-2, synaptotagmin, and
      alphaII-spectrin were found to be elevated after TBI. Differential changes in the
      above mentioned proteins were confirmed by quantitative immunoblotting. Results
      from this work provide insight into mechanisms of traumatic brain injury and
      yield putative biochemical markers to potentially facilitate patient management
      by monitoring the severity, progression, and treatment of injury.

PMID- 16801362
TI  - Breast masses: computer-aided diagnosis with serial mammograms.
AB  - PURPOSE: To retrospectively evaluate effects of computer-aided diagnosis (CAD)
      involving an interval change classifier (which uses interval change information
      extracted from prior and current mammograms and estimates a malignancy rating) on
      radiologists' accuracy in characterizing masses on two-view serial mammograms as
      malignant or benign. MATERIALS AND METHODS: The data collection protocol had
      institutional review board approval. Patient informed consent was waived for this
      HIPAA-compliant retrospective study. Ninety temporal pairs of two-view serial
      mammograms (depicting 47 malignant and 43 benign biopsy-proved masses) were
      obtained from 68 patient files and were digitized. Biopsy was the reference
      standard. Eight Mammography Quality Standards Act of 1992-accredited radiologists
      and two breast imaging fellows assessed digitized two-view temporal pairs (in
      preselected regions of interest only) by estimating likelihood of malignancy and
      Breast Imaging Reporting and Data System (BI-RADS) category without and with CAD.
      Observers' rating data were analyzed with Dorfman-Berbaum-Metz (DBM) multireader
      multicase method. Statistical significance of differences was estimated with the
      DBM method and Student two-tailed paired t test. RESULTS: Average area under the
      receiver operating characteristic curve for likelihood of malignancy across the
      10 observers was 0.83 (range, 0.74-0.88) without CAD and improved to 0.87 (range,
      0.80-0.92) with CAD (P < .05). The average partial area index above a sensitivity
      of 0.90 for likelihood of malignancy was 0.35 (range, 0.13-0.54) without CAD and
      0.49 (range, 0.18-0.73) with CAD--a nonsignificant improvement (P = .11). For BI
      RADS assessment, it was estimated that with CAD, six radiologists would correctly
      recommend additional biopsies for malignant masses (range, 4.3%-10.6%) and five
      would correctly recommend reduction of biopsy (ie, fewer biopsies) for benign
      masses (range, 2.3%-9.3%). However, five radiologists would incorrectly recommend
      additional biopsy for benign masses (range, 2.3%-14.0%), and one would
      incorrectly recommend reduction of biopsy (4.3%). CONCLUSION: CAD involving
      interval change analysis of preselected regions of interest can significantly
      improve radiologists' accuracy in classifying masses on digitized screen-film
      mammograms as malignant or benign.

PMID- 16801363
TI  - Cartilaginous defects of the femorotibial joint: accuracy of coronal short
      inversion time inversion-recovery MR sequence.
AB  - PURPOSE: To retrospectively assess the diagnostic performance of the short
      inversion time inversion-recovery (STIR) magnetic resonance (MR) sequence for
      depiction and classification of articular cartilaginous lesions in femorotibial
      joint, with arthroscopy as reference standard. MATERIALS AND METHODS:
      Institutional review board did not require approval and informed consent for
      review of patients' records or images. All patients (and parents of underage
      patients) agreed to use of their data. Two musculoskeletal radiologists
      independently analyzed femorotibial cartilage on coronal STIR images from 84 knee
      MR examinations in 83 patients (48 male patients [49 knees], 35 female patients;
      mean age, 39.5 years). Slightly modified Outerbridge classification was used:
      grade 0, normal cartilage; grade 1, softening or swelling; grade 2, partial
      thickness defect; grade 3, fissuring to the level of the subchondral bone; and
      grade 4, exposed subchondral bone. Arthroscopy performed within 15 weeks was the
      standard of reference. Classification for arthroscopy differed only in definition
      of grade 1 (softening or swelling of cartilage). Sensitivity, specificity,
      accuracy, positive and negative predictive values, and weighted kappa values were
      calculated to assess interobserver reliability. RESULTS: At arthroscopy, 212
      (63%) of 336 surfaces were classified as grade 0 (normal); 37 (11%), as grade 1
      abnormalities; 30 (9%), as grade 2 lesions; 25 (7%), as grade 3 lesions; and 32
      (10%), as grade 4 lesions. Grades 0 and 1 were considered normal; grades 2-4, as
      abnormal. For detection of contour defects of the cartilaginous surface, coronal
      STIR MR imaging had sensitivity values of 77% and 76%, specificity values of 96%
      and 89%, accuracy values of 91% and 85%, positive predictive values of 86% and
      70%, and negative predictive values of 92% and 91% for readers 1 and 2,
      respectively. Weighted kappa value was 0.63. CONCLUSION: Contour defects of
      femorotibial cartilage can be detected with reasonable accuracy with routine STIR
      sequence.

PMID- 16801364
TI  - Relapsing polychondritis: prevalence of expiratory CT airway abnormalities.
AB  - PURPOSE: To retrospectively determine the prevalence of expiratory computed
      tomographic (CT) abnormalities, including malacia and air trapping, in patients
      with relapsing polychondritis and to retrospectively determine the frequency with
      which expiratory abnormalities are accompanied by inspiratory abnormalities on CT
      scans. MATERIALS AND METHODS: Institutional review board approval was obtained,
      and informed consent was not required for this retrospective HIPAA-compliant
      study. A computerized hospital information system was used to identify all
      patients with clinically diagnosed or biopsy-proved relapsing polychondritis who
      were referred for CT airway imaging during a 17-month period. The study cohort
      comprised 18 patients (15 women, three men; mean age, 47 years; age range, 20-71
      years). Multidetector helical CT was performed in all patients by using a
      standard protocol, which included end-inspiratory and dynamic expiratory
      volumetric imaging. Two observers who were blinded to the original scan
      interpretations simultaneously reviewed CT scans. Findings were recorded in
      consensus. Dynamic expiratory CT scans were assessed for malacia that involved
      the trachea and main bronchi (reduction in cross-sectional area of more than 50%)
      and for air trapping (failure of lung parenchyma to increase in attenuation
      during expiration). Air trapping was visually classified according to pattern and
      extent (lobular, segmental, lobar, or whole lung). Inspiratory CT scans were
      evaluated for tracheal and bronchial stenosis (>25% luminal diameter narrowing
      compared with a corresponding uninvolved segment), wall thickening (>2 mm), and
      calcification. RESULTS: Expiratory CT abnormalities were present in 17 (94%) of
      18 patients and included malacia in 13 patients (72%) and air trapping in 17
      patients (94%). Inspiratory CT abnormalities were found in eight (47%) of 17
      patients who had expiratory CT abnormalities. Calcification of the airway walls
      was present in seven (39%) of 18 patients. All patients who had inspiratory CT
      abnormalities demonstrated expiratory CT abnormalities. CONCLUSION: Expiratory CT
      abnormalities were present in the majority of patients with relapsing
      polychondritis who were referred for airway imaging, yet only half of these
      patients demonstrated abnormalities on routine inspiratory CT scans. Thus,
      dynamic expiratory CT should be a standard component of imaging assessment in
      patients with relapsing polychondritis.

PMID- 16801365
TI  - Renovascular impedance correlates with portal pressure in patients with liver
      cirrhosis.
AB  - PURPOSE: To prospectively evaluate, in patients with liver cirrhosis, the
      correlation between the renovascular impedance measured by using color flow and
      pulsed wave Doppler ultrasonography (US) and the portal pressure measured by
      using the hepatic venous pressure gradient (HVPG). MATERIALS AND METHODS: The
      study was approved by the senior staff committee (comparable to institutional
      review board) of the university hospital, and written informed consent was
      obtained from all patients. Thirty-one patients with cirrhosis (22 men, nine
      women; mean age, 57.6 years +/- 8.8 [standard deviation]) and esophageal varices
      were consecutively enrolled in the study. Having fasted, the patients underwent
      color flow and pulsed wave Doppler US of the right interlobar renal artery (RRA)
      and the left interlobar renal artery (LRA). The resistance index (RI) and
      pulsatility index (PI) were determined. On the same day, with fluoroscopic
      guidance, a 5-F balloon-tipped catheter was advanced, via the right basilic vein,
      into the right hepatic vein; HVPG was calculated as the difference between the
      wedged and free hepatic pressures. All measurements were performed in triplicate,
      and permanent tracings were recorded. Correlations were made by using the Pearson
      test. The positive predictive value of renovascular impedance for detection of
      severe portal hypertension was determined. RESULTS: Mean RI and PI values were
      0.67 +/- 0.07 and 1.21 +/- 0.25, respectively, for the RRA, and 0.68 +/- 0.07 and
      1.24 +/- 0.26, respectively, for the LRA. All patients had portal hypertension
      (mean HVPG, 19.3 mm Hg +/- 4.7; range, 11.5-33.5 mm Hg). Neither portal pressure
      nor renal impedance correlated with Child-Pugh score for cirrhosis. Renal artery
      impedance indexes correlated with the HVPG (for RRA RI: R = 0.424, P = .03; for
      RRA PI: R = 0.402, P = .04; for LRA RI: R = 0.352, P = .05; for LRA PI: R =
      0.393, P = .02). A higher-than-normal renal impedance had a high positive
      predictive value (RRA RI and PI, 100%; LRA RI, 92%; LRA PI, 84%) for the
      detection of severe portal hypertension. CONCLUSION: Renovascular impedance had a
      direct correlation with HVPG.

PMID- 16801366
TI  - MR defecography in patients with fecal incontinence: imaging findings and their
      effect on surgical management.
AB  - PURPOSE: To retrospectively evaluate magnetic resonance (MR) defecography
      findings in patients with fecal incontinence who were evaluated for surgical
      treatment and to assess the influence of MR defecography on surgical therapy.
      MATERIALS AND METHODS: Institutional review board approval was obtained. Informed
      consent was waived; however, written informed consent for imaging was obtained.
      Fifty patients (44 women, six men; mean age, 61 years) with fecal incontinence
      were placed in a sitting position and underwent MR defecography performed with an
      open-configuration MR system. Midsagittal T1-weighted MR images were obtained at
      rest, at maximal contraction of the sphincter, and at defecation. Images were
      prospectively and retrospectively reviewed by two independent observers for a
      variety of findings. Interobserver agreement was analyzed by calculating kappa
      statistics. Prospective interpretation of MR defecography findings was used to
      influence surgical therapy, and retrospective interpretation was used for
      concomitant pelvic floor disorders. RESULTS: MR defecography revealed rectal
      descent of more than 6 cm (relative to the pubococcygeal line) in 47 (94%) of 50
      patients. A bladder descent of more than 3 cm was present in 20 (40%) of 50
      patients, and a vaginal vault descent of more than 3 cm was present in 19 (43%)
      of 44 women. Moreover, 17 (34%) anterior proctoceles, 16 (32%) enteroceles, and
      10 (20%) rectal prolapses were noted. Interobserver agreement was good to
      excellent (kappa = 0.6-0.91) for image analysis results. MR defecography findings
      led to changes in the surgical approach in 22 (67%) of 33 patients who underwent
      surgery. CONCLUSION: MR defecography may demonstrate a variety of abnormal
      findings in patients who are considered candidates for surgical therapy for fecal
      incontinence, and the findings may influence the surgical treatment that is
      subsequently chosen. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/2402050648/DC1

PMID- 16801367
TI  - Quantification of lung tumor volume and rotation at 3D dynamic parallel MR
      imaging with view sharing: preliminary results.
AB  - The purpose of this study was to prospectively evaluate the volumes and rotations
      of pulmonary nodules during respiration by using three-dimensional fast low-angle
      shot dynamic magnetic resonance (MR) imaging (1.5/0.6 [repetition time msec/echo
      time msec], 3.8 x 3.8 x 3.8-mm voxel size, imaging time per three-dimensional
      data set of 1 second). The feasibility of the technique was verified by using 130
      , 40-, and 12-cm3 phantoms made of meatballs and in five patients with solitary
      intrapulmonary tumors (four men, one woman; median age, 60 years) at computed
      tomography and histologic analysis. All patients provided written informed
      consent, and the study was institutional review board approved. It was proved
      that there were no substantial differences among the 21 algorithms used to
      correct partial volume effects. The most precise algorithm (r > 0.9, P < .01)
      used to correct partial volume effects--with which mean phantom volumes of 120.8
      cm3 +/- 4.1, 36.1 cm3 +/- 3.98, and 13.1 cm3 +/- 1.5 were calculated--yielded a
      root mean square error of 14%. The MR imaging-derived nodule volume and rotation
      during respiration could be quantified by using oriented bounding box techniques.

PMID- 16801368
TI  - Adrenal lesions: attenuation measurement differences between CT scanners.
AB  - PURPOSE: To retrospectively compare unenhanced computed tomographic scans of the
      same adrenal lesion obtained with two different manufacturers' multidetector
      scanners to assess whether there are differences in attenuation measurements.
      MATERIALS AND METHODS: The study was approved by the local ethical committee,
      which waived patient consent, and was conducted in compliance with HIPAA.
      Electronic searching revealed patients with adrenal nodules scanned with both a
      Siemens 16-detector row scanner and one of eight GE Medical Systems multi
      detector row scanners between January 2000 and September 2004 without the use of
      intravenous contrast material. Lesions were characterized by using histologic
      findings, fat content, or size stability. Size stability for 6 months was
      required unless both scans were obtained within 21 days of each other. Two
      radiologists independently measured lesion attenuation for regression analysis.
      Lesions considered benign (< or = 10 HU) on one scan and indeterminate (> 10 HU)
      on the other were separately analyzed, and technical parameters of scanning were
      compared. RESULTS: There were 47 patients (27 men, 20 women; age range, 40-86
      years; mean age, 64 years) with four metastases, 42 adenomas, and one myelolipoma
      (long-axis length, 10-85 mm; mean, 24 mm). GE scans were obtained with four
      detector row scanners (n = 32), an eight-detector row scanner (n = 2), and 16
      detector row scanners (n = 13). Correlation between the two readers was 0.99 for
      both Siemens and GE scan attenuation measurements. The slope of regression lines
      for both readers plotting GE attenuation (y-axis) against Siemens attenuation (x
      axis) was less than 1, which indicated a slight but statistically significant
      tendency for GE scans to have lower attenuations than do Siemens scans. For both
      readers, there were more lesions indeterminate (> 10 HU) on Siemens scans but
      benign (< or = 10 HU) on GE scans than the reverse (McNemar test, P < .02 for
      reader 1, not significant for reader 2). Average Siemens and GE scan technical
      parameters were similar. CONCLUSION: There are only slight differences in
      attenuation of adrenal nodules measured on scans obtained with different
      scanners.

PMID- 16801369
TI  - Articular cartilage of the knee: rapid three-dimensional MR imaging at 3.0 T with
      IDEAL balanced steady-state free precession--initial experience.
AB  - Institutional review board approval and informed consent were obtained for this
      HIPAA-compliant study. In this study, iterative decomposition of water and fat
      with echo asymmetry and least-squares estimation (IDEAL) balanced steady-state
      free precession (bSSFP), fat-suppressed bSSFP, and fat-suppressed spoiled
      gradient-echo (GRE) sequences for 3.0-T magnetic resonance (MR) imaging of
      articular knee cartilage were prospectively compared in five healthy volunteers.
      Cartilage and fluid signal-to-noise ratio (SNR), cartilage-fluid contrast-to
      noise ratio (CNR), SNR efficiency, CNR efficiency, image quality, and fat
      suppression were compared. Fat-suppressed bSSFP and IDEAL bSSFP had higher SNR
      efficiency of cartilage (P < .01) than did GRE. IDEAL bSSFP had higher cartilage
      fluid CNR efficiency than did fat-suppressed bSSFP or GRE (P < .01). Fat
      suppressed bSSFP and IDEAL bSSFP had higher image quality than did GRE (P < .01).
      GRE and IDEAL bSSFP had significantly better fat-water separation or fat
      saturation than did fat-suppressed bSSFP (P < .05). IDEAL bSSFP is a promising
      method for imaging articular knee cartilage.

PMID- 16801370
TI  - Virtual autopsy: preliminary experience in high-velocity gunshot wound victims.
AB  - PURPOSE: To retrospectively assess virtual autopsy performed with multidetector
      computed tomography (CT) for the forensic evaluation of gunshot wound victims.
      MATERIALS AND METHODS: The institutional review board approved this HIPAA
      compliant study and did not require informed consent of the next of kin. Thirteen
      consecutive male gunshot wound victims (mean age, 27 years) were scanned with 16
      section multidetector CT prior to routine autopsy. Retrospectively, the total
      body nonenhanced scans were interpreted at a three-dimensional workstation by
      radiologists blinded to autopsy findings. Images were evaluated for lethal wound,
      number and location of wound tracks, injured structures, and metal fragment
      location. After image review, autopsy reports and photographs were compared with
      the images and interpretations to validate the multidetector CT determinations.
      RESULTS: Multidetector CT aided in correct identification of all lethal wounds,
      and metallic fragment location was always precise. In four cases, multidetector
      CT aided in accurate assessment of organ injuries and lethal wounds but led to
      underestimation of the number of wounds if comingling paths occurred. In two
      cases of a chest wound, multidetector CT aided in accurate assessment of the
      chest as having the lethal wound but failed to help identify specific sites of
      hemorrhage. In two cases of craniofacial injury, the path of the wound was not
      clear. Autopsy revealed a total of 78 wound tracks (mean, 6; range, 1-24). Ten
      (13%) wound tracks were not identified at multidetector CT (six upper extremity
      wounds and four thigh wounds). In two cases, findings missed at autopsy (fracture
      of the cervical spine, bullet fragments in the posterior area of the neck) were
      identified at multidetector CT. CONCLUSION: Multidetector CT can aid prediction
      of lethal wounds and location of metallic fragments.

PMID- 16801371
TI  - MR guidance of targeted injections into border and core of scarred myocardium in
      pigs.
AB  - PURPOSE: To use (a) dysprosium-based contrast agent (sprodiamide) to confirm the
      site of myocardial injection and (b) T1-enhancing magnetic resonance (MR)
      contrast media to mark the myocardial target and T2*-enhancing contrast media to
      demonstrate injection sites in the margins or core of infarction on delayed
      contrast-enhanced images. MATERIALS AND METHODS: Approval of the institutional
      committee on animal research was obtained. A phantom and six pigs subjected to
      chronic infarction (8 weeks) underwent MR-guided experiments. At inversion
      recovery gradient-echo imaging, gadoterate meglumine (0.1 mmol/kg) was
      intravenously administered to delineate scar tissue. A catheter fitted with
      multiple receiver coils was used to visualize catheter navigation and injection
      sites. A steady-state free precession (balanced fast field-echo) sequence was
      used for MR fluoroscopy. A high-resolution multiphase balanced gradient-echo cine
      MR sequence was used after intramyocardial deposition of sprodiamide. The border
      and core of scarred myocardium were characterized histopathologically. The 95%
      confidence interval (CI) was used to demonstrate the range, extent of
      hyperenhanced and hypoenhanced regions after contrast media administration.
      RESULTS: In the phantom and in vivo, the actively guided catheter produced a high
      signal intensity at the terminal portion of the shaft and tip. Scarred myocardium
      was recognized as a bright region on gadoterate meglumine-enhanced images.
      Intramyocardial injection of sprodiamide caused local and persistent signal
      intensity loss, and the extent was volume dependent on balanced fast field-echo
      and T2-weighted turbo spin-echo images. At 5 minutes after administration of 0.2,
      0.4, and 0.6 mL of sprodiamide, the 95% CIs of the extents of the hypoenhanced
      regions were 0.08%, 0.23%; 0.27%, 0.51%; and 0.46%, 0.70%, respectively, of left
      ventricular (LV) surface area (P < .05, paired t test). Failure of
      intramyocardial injection was confirmed by a brief signal loss of LV chamber
      blood. CONCLUSION: Sprodiamide allows visualization of injection sites within
      enhanced infarction. A catheter with integrated receiver coils aided in effective
      catheter guidance and precise intramyocardial injection.

PMID- 16801372
TI  - Effect of obesity on image quality: fifteen-year longitudinal study for
      evaluation of dictated radiology reports.
AB  - PURPOSE: To retrospectively assess the effect of obesity on image quality, as
      determined from dictated radiology reports filed between 1989 and 2003. MATERIALS
      AND METHODS: Institutional review board approval was obtained for this HIPAA
      compliant study; informed consent was not required. Electronic records were
      searched for radiology reports with the phrase "limited due to body habitus"
      (hereafter, "habitus limited") filed between 1989 and 2003; reports were
      retrospectively reviewed. Habitus limited was qualified as the search phrase by
      auditing radiologic images and patient weights. Trends in the number of habitus
      limited reports were calculated for each year, and linear regression analysis was
      performed. The number of habitus-limited reports was also compared between
      modalities within a year and within each modality across 15 years. The trend was
      correlated with the prevalence of obesity in Massachusetts by using the Pearson
      correlation coefficient. RESULTS: There was a significant difference (P < .001)
      between the weight of patients with habitus-limited reports and the weight of
      patients with reports that were not habitus limited. Overall, 7778 (0.15%) of 5
      253 014 reports were habitus limited. Between 1989 and 2003, there was a linear
      increase of 0.010% per year (95% confidence interval: 0.007%, 0.013%; P < .001).
      There was a positive correlation between the increased number of habitus-limited
      reports and the increased prevalence of obese individuals in Massachusetts
      between 1991 and 2001. The modality most commonly associated with habitus-limited
      reports was abdominal ultrasonography. CONCLUSION: There was a small but
      progressive increase in the number of habitus-limited radiology reports between
      1989 and 2003.

PMID- 16801373
TI  - Contrast enhancement of central nervous system lesions: multicenter
      intraindividual crossover comparative study of two MR contrast agents.
AB  - PURPOSE: To prospectively compare gadobenate dimeglumine with gadopentetate
      dimeglumine (0.1 mmol per kilogram body weight) for enhanced magnetic resonance
      (MR) imaging of central nervous system (CNS) lesions. MATERIALS AND METHODS: This
      study was HIPAA-compliant at U.S. centers and was conducted at all centers
      according to the Good Clinical Practice standard. Institutional review board and
      regulatory approval were granted; written informed consent was obtained. Seventy
      nine men and 78 women (mean age, 50.5 years +/- 14.4 [standard deviation]) were
      randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally
      separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed
      by gadopentetate was administered in group A; order of administration was
      reversed in group B. Contrast agent administration (volume, speed of injection),
      imaging parameters before and after injection, and time between injections and
      postinjection acquisitions were identical for both examinations. Three blinded
      neuroradiologists evaluated images by using objective image interpretation
      criteria for diagnostic information end points (lesion border delineation,
      definition of disease extent, visualization of internal morphologic features of
      the lesion, enhancement of the lesion) and quantitative parameters (percentage of
      lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference
      in terms of lesion conspicuity, detectability, and diagnostic confidence was
      assessed. Between-group comparisons were performed with Wilcoxon signed rank
      test. RESULTS: Readers 1, 2, and 3 demonstrated overall preference for gadobenate
      in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10,
      and six patients, respectively (P < .0001). Significant (P < .0001) preference
      for gadobenate was demonstrated for diagnostic information end points, percentage
      of lesion enhancement, and CNR. Superiority of gadobenate was significant (P <
      .001) in patients with intraaxial and extraaxial lesions. CONCLUSION: Gadobenate
      compared with gadopentetate at an equivalent dose provides significantly better
      enhancement and diagnostic information for CNS MR imaging.

PMID- 16801374
TI  - Occupational exposure and laryngeal and hypopharyngeal cancer risk in central and
      eastern Europe.
AB  - A multicenter case-control study was conducted during 1999-2002 in four European
      countries (Poland, Romania, Russia, and Slovakia) to evaluate the role of
      occupational exposures in risk of laryngeal/hypopharyngeal cancer. Male cancer
      cases (34 hypopharyngeal, 316 laryngeal) with full data on occupational history
      and nonoccupational factors were compared with 728 hospital controls for
      occupational exposure to 73 suspected carcinogens. Occupational history was
      evaluated by industrial hygienists blinded to case/control status. Elevated risks
      for ever exposure to coal dust were found for both hypopharyngeal (odds ratio
      (OR) = 4.19, 95% confidence interval (CI): 1.18, 14.89) and laryngeal (OR = 1.81,
      95% CI: 0.94, 3.47) cancer, with clear dose-response patterns. Inclusion of a 20
      year lag in the analysis strengthened these associations. Hypopharyngeal cancer
      risk was also significantly associated with exposure to mild steel dust (OR =
      3.04, 95% CI: 1.39, 6.64) and iron compounds and fumes (OR = 2.74, 95% CI: 1.29,
      5.84), without clear dose-response relations. Laryngeal cancer was significantly
      associated with exposure to hard-alloys dust (OR = 2.23, 95% CI: 1.08, 4.57) and
      chlorinated solvents (OR = 2.18, 95% CI: 1.03, 4.61), without dose-response
      relations. A possible link between high formaldehyde exposure and laryngeal
      cancer was suggested. No association was found for exposure to asbestos or
      inorganic acid mists. These data indicate that occupational exposure to coal dust
      may play a role in laryngeal and hypopharyngeal cancer. Other possible relations
      need further evaluation.

PMID- 16801376
TI  - Factors associated with colorectal cancer risk perception: the role of polyps and
      family history.
AB  - It is unclear how objective risk factors influence the factors associated with
      colorectal cancer (CRC) risk perception. The goals of this study were to
      investigate factors associated with perceived risk of CRC and to explore how
      these relationships were modified by personal history of polyps or family history
      of CRC. The study involved a mailed questionnaire completed by 1646 men and women
      aged 50-75 years, which assessed perceived risk, demographic and health history
      variables and CRC worry. Participants were patients of primary care providers in
      a community medical group in central Massachusetts. The study sample seemed to
      have a generally accurate perception of CRC risk, which was appropriately
      increased in the presence of known risk factors. In multivariable analyses that
      controlled for all measured covariates, financial situation modified the
      association between perceived risk and a personal history of polyps, while age
      and insurance status modified the association between perceived risk and family
      history of CRC. CRC worry, self-reported health, personal history of other cancer
      and compliance with screening guidelines remained significant predictors of
      perceived risk. Potential interactions between objective risk factors and
      socioeconomic characteristics should be further explored in longitudinal studies.

PMID- 16801375
TI  - Plasma lycopene, other carotenoids, and the risk of type 2 diabetes in women.
AB  - The authors conducted a nested case-control study from 1992 to 2003 among US
      women aged 45 years or older and free from cardiovascular disease and cancer to
      examine the prospective association among plasma lycopene, other carotenoids, and
      the risk of developing type 2 diabetes. During 10 years of follow-up, 470 cases
      of incident type 2 diabetes were selected and individually matched on age (+/- 1
      year) and follow-up time to 470 nondiabetic controls. Baseline plasma levels of
      lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, and
      lutein/zeaxanthin were similar in cases and controls (all p > 0.05). A possible
      crude inverse association between plasma lycopene and risk of type 2 diabetes was
      attenuated upon multivariate adjustment. After control for plasma total
      cholesterol and known diabetes risk factors, the multivariate odds ratios of type
      2 diabetes in the highest versus the lowest quartile of plasma carotenoids were
      1.13 (95% confidence interval (CI): 0.60, 2.13) for lycopene, 1.27 (95% CI: 0.63,
      2.57) for alpha-carotene, 1.10 (95% CI: 0.57, 2.13) for beta-carotene, 0.91 (95%
      CI: 0.46, 1.81) for beta-cryptoxanthin, and 1.35 (95% CI: 0.68, 2.69) for
      lutein/zeaxanthin. There was no prospective association between baseline plasma
      carotenoids and the risk of type 2 diabetes in middle-aged and older women.

PMID- 16801377
TI  - Brain activity related to working memory and distraction in children and adults.
AB  - In order to retain information in working memory (WM) during a delay, distracting
      stimuli must be ignored. This important ability improves during childhood, but
      the neural basis for this development is not known. We measured brain activity
      with functional magnetic resonance imaging in adults and 13-year-old children.
      Data were analyzed with an event-related design to isolate activity during cue,
      delay, distraction, and response selection. Adults were more accurate and less
      distractible than children. Activity in the middle frontal gyrus and
      intraparietal cortex was stronger in adults than in children during the delay,
      when information was maintained in WM. Distraction during the delay evoked
      activation in parietal and occipital cortices in both adults and children.
      However, distraction activated frontal cortex only in children. The larger
      frontal activation in response to distracters presented during the delay may
      explain why children are more susceptible to interfering stimuli.

PMID- 16801378
TI  - Additive effects of serotonin transporter and tryptophan hydroxylase-2 gene
      variation on emotional processing.
AB  - Prior studies reported that functional variants of both the serotonin transporter
      (5-HTT) and tryptophan hydroxylase-2 genes (TPH2), 2 key regulators of the
      serotonergic signaling pathway, modulate amygdala activation during emotional
      processing. We addressed the question whether these 2 gene variants modulate each
      other, using an emotional picture-processing task. Specifically, we measured
      event-related potentials (ERPs) during a passive emotional picture perception
      task, focusing on ERPs for the early posterior negativity (EPN) around 240 ms and
      for the slow wave starting at 315 ms. We found evidence for increased neural
      activity at 240 ms in individuals who carried 1 or 2 copies of the low-expression
      short variant of the 5-HTT. Carriers of T variant of the TPH2 also showed a
      tendency toward increased neural activity at 240 ms. Moreover, we observed an
      additive effect of both genotypes for EPN, with highest neural activity to
      emotional stimuli in individuals carrying combination of both short variant of 5
      HTT and T variant of TPH2. Our results indicate that both the 5-HTT and the TPH2
      genotypes modulate the sensory encoding of affective stimuli during early steps
      of visual processing and reveal additive effects of 2 genes in the serotonergic
      control of emotion regulation.

PMID- 16801379
TI  - Variation in the human TAS1R taste receptor genes.
AB  - We have performed a comprehensive evaluation of single-nucleotide polymorphisms
      (SNPs) and haplotypes in the human TAS1R gene family, which encodes receptors for
      sweet and umami tastes. Complete DNA sequences of TAS1R1-, TAS1R2-, and TAS1R3
      coding regions, obtained from 88 individuals of African, Asian, European, and
      Native American origin, revealed substantial coding and noncoding diversity:
      polymorphisms are common in these genes, and polymorphic sites and SNP
      frequencies vary widely in human populations. The genes TAS1R1 and TAS1R3, which
      encode proteins that act as a dimer to form the umami (glutamate) taste receptor,
      showed less variation than the TAS1R2 gene, which acts as a dimer with TAS1R3 to
      form the sweet taste receptor. The TAS1R3 gene, which encodes a subunit common to
      both the sweet and umami receptors, was the most conserved. Evolutionary genetic
      analysis indicates that these variants have come to their current frequencies
      under natural selection during population growth and support the view that the
      coding sequence variants affect receptor function. We propose that human
      populations likely vary little with respect to umami perception, which is
      controlled by one major form of the receptor that is optimized for detecting
      glutamate but may vary much more with respect to sweet perception.

PMID- 16801382
TI  - Mechanism of the inhibition of Ca2+-activated Cl- currents by phosphorylation in
      pulmonary arterial smooth muscle cells.
AB  - The aim of the present study was to provide a mechanistic insight into how
      phosphatase activity influences calcium-activated chloride channels in rabbit
      pulmonary artery myocytes. Calcium-dependent Cl- currents (I(ClCa)) were evoked
      by pipette solutions containing concentrations between 20 and 1000 nM Ca2+ and
      the calcium and voltage dependence was determined. Under control conditions with
      pipette solutions containing ATP and 500 nM Ca2+, I(ClCa) was evoked immediately
      upon membrane rupture but then exhibited marked rundown to approximately 20% of
      initial values. In contrast, when phosphorylation was prohibited by using pipette
      solutions containing adenosine 5'-(beta,gamma-imido)-triphosphate (AMP-PNP) or
      with ATP omitted, the rundown was severely impaired, and after 20 min dialysis,
      I(ClCa) was approximately 100% of initial levels. I(ClCa) recorded with AMP-PNP
      containing pipette solutions were significantly larger than control currents and
      had faster kinetics at positive potentials and slower deactivation kinetics at
      negative potentials. The marked increase in I(ClCa) was due to a negative shift
      in the voltage dependence of activation and not due to an increase in the
      apparent binding affinity for Ca2+. Mathematical simulations were carried out
      based on gating schemes involving voltage-independent binding of three Ca2+, each
      binding step resulting in channel opening at fixed calcium but progressively
      greater "on" rates, and voltage-dependent closing steps ("off" rates). Our model
      reproduced well the Ca2+ and voltage dependence of I(ClCa) as well as its kinetic
      properties. The impact of global phosphorylation could be well mimicked by
      alterations in the magnitude, voltage dependence, and state of the gating
      variable of the channel closure rates. These data reveal that the phosphorylation
      status of the Ca2+-activated Cl- channel complex influences current generation
      dramatically through one or more critical voltage-dependent steps.

PMID- 16801381
TI  - Regulation of maximal open probability is a separable function of Ca(v)beta
      subunit in L-type Ca2+ channel, dependent on NH2 terminus of alpha1C
      (Ca(v)1.2alpha).
AB  - beta subunits (Ca(v)beta) increase macroscopic currents of voltage-dependent Ca2+
      channels (VDCC) by increasing surface expression and modulating their gating,
      causing a leftward shift in conductance-voltage (G-V) curve and increasing the
      maximal open probability, P(o,max). In L-type Ca(v)1.2 channels, the Ca(v)beta
      induced increase in macroscopic current crucially depends on the initial segment
      of the cytosolic NH2 terminus (NT) of the Ca(v)1.2alpha (alpha1C) subunit. This
      segment, which we term the "NT inhibitory (NTI) module," potently inhibits long
      NT (cardiac) isoform of alpha1C that features an initial segment of 46 amino acid
      residues (aa); removal of NTI module greatly increases macroscopic currents. It
      is not known whether an NTI module exists in the short-NT (smooth muscle/brain
      type) alpha(1C) isoform with a 16-aa initial segment. We addressed this question,
      and the molecular mechanism of NTI module action, by expressing subunits of
      Ca(v)1.2 in Xenopus oocytes. NT deletions and chimeras identified aa 1-20 of the
      long-NT as necessary and sufficient to perform NTI module functions. Coexpression
      of beta2b subunit reproducibly modulated function and surface expression of
      alpha1C, despite the presence of measurable amounts of an endogenous Ca(v)beta in
      Xenopus oocytes. Coexpressed beta2b increased surface expression of alpha1C
      approximately twofold (as demonstrated by two independent immunohistochemical
      methods), shifted the G-V curve by approximately 14 mV, and increased P(o,max)
      2.8-3.8-fold. Neither the surface expression of the channel without Ca(v)beta nor
      beta2b-induced increase in surface expression or the shift in G-V curve depended
      on the presence of the NTI module. In contrast, the increase in P(o,max) was
      completely absent in the short-NT isoform and in mutants of long-NT alpha1C
      lacking the NTI module. We conclude that regulation of P(o,max) is a discrete,
      separable function of Ca(v)beta. In Ca(v)1.2, this action of Ca(v)beta depends on
      NT of alpha1C and is alpha1C isoform specific.

PMID- 16801383
TI  - An electrically coupled network of skeletal muscle in zebrafish distributes
      synaptic current.
AB  - Fast and slow skeletal muscle types are readily distinguished in larval zebrafish
      on the basis of differences in location and orientation. Additionally, both
      muscle types are compact, rendering them amenable to in vivo patch clamp study of
      synaptic function. Slow muscle mediates rhythmic swimming, but it does so purely
      through synaptic drive, as these cells are unable to generate action potentials.
      Our patch clamp recordings from muscle pairs of zebrafish reveal a network of
      electrical coupling in slow muscle that allows sharing of synaptic current within
      and between segmental boundaries of the tail. The synaptic current exhibits slow
      kinetics (tau(decay) approximately 4 ms), which further facilitates passage
      through the low pass filter, a consequence of the electrically coupled network.
      In contrast to slow muscle, fast skeletal muscle generates action potentials to
      mediate the initial rapid component of the escape response. The combination of
      very weak electrical coupling and synaptic kinetics (tau(decay) <1 ms) too fast
      for the network low pass filter minimizes intercellular sharing of synaptic
      current in fast muscle. These differences between muscle types provide insights
      into the physiological role(s) of electrical coupling in skeletal muscle. First,
      intrasegmental coupling among slow muscle cells allows effective transfer of
      synaptic currents within tail segments, thereby minimizing differences in
      synaptic depolarization. Second, a fixed intersegmental delay in synaptic current
      transit, resulting from the low pass filter properties of the slow muscle
      network, helps coordinate the rostral-caudal wave of contraction.

PMID- 16801384
TI  - Palytoxin-induced effects on partial reactions of the Na,K-ATPase.
AB  - The interaction of palytoxin with the Na,K-ATPase was studied by the
      electrochromic styryl dye RH421, which monitors the amount of ions in the
      membrane domain of the pump. The toxin affected the pump function in the state P
      E2, independently of the type of phosphorylation (ATP or inorganic phosphate).
      The palytoxin-induced modification of the protein consisted of two steps: toxin
      binding and a subsequent conformational change into a transmembrane ion channel.
      At 20 degrees C, the rate-limiting reaction had a forward rate constant of 10(5)
      M(-1)s(-1) and a backward rate constant of about 10(-3) s(-1). In the palytoxin
      modified state, the binding affinity for Na+ and H+ was increased and reached
      values between those obtained in the E1 and P-E2 conformation under physiological
      conditions. Even under saturating palytoxin concentrations, the ATPase activity
      was not completely inhibited. In the Na/K mode, approximately 50% of the enzyme
      remained active in the average, and in the Na-only mode 25%. The experimental
      findings indicate that an additional exit from the inhibited state exists. An
      obvious reaction pathway is a slow dephosphorylation of the palytoxin-inhibited
      state with a time constant of approximately 100 s. Analysis of the effect of
      blockers of the extracellular and cytoplasmic access channels, TPA+ and Br2
      Titu3+, respectively, showed that both access channels are part of the ion
      pathway in the palytoxin-modified protein. All experiments can be explained by an
      extension of the Post-Albers cycle, in which three additional states were added
      that branch off in the P-E2 state and lead to states in which the open-channel
      conformation is introduced and returns into the pump cycle in the occluded E2
      state. The previously suggested molecular model for the channel state of the Na,K
      ATPase as a conformation in which both gates between binding sites and aqueous
      phases are simultaneously in their open state is supported by this study.

PMID- 16801385
TI  - Binding of a gating modifier toxin induces intersubunit cooperativity early in
      the Shaker K channel's activation pathway.
AB  - Potassium currents from voltage-gated Shaker K channels activate with a sigmoid
      rise. The degree of sigmoidicity in channel opening kinetics confirms that each
      subunit of the homotetrameric Shaker channel undergoes more than one
      conformational change before the channel opens. We have examined effects of two
      externally applied gating modifiers that reduce the sigmoidicity of channel
      opening. A toxin from gastropod mucus, 6-bromo-2-mercaptotryptamine (BrMT), and
      divalent zinc are both found to slow the same conformational changes early in
      Shaker's activation pathway. Sigmoidicity measurements suggest that zinc slows a
      conformational change independently in each channel subunit. Analysis of
      activation in BrMT reveals cooperativity among subunits during these same early
      steps. A lack of competition with either agitoxin or tetraethylammonium indicates
      that BrMT binds channel subunits outside of the external pore region in an
      allosterically cooperative fashion. Simulations including negatively cooperative
      BrMT binding account for its ability to induce gating cooperativity during
      activation. We conclude that cooperativity among K channel subunits can be
      greatly altered by experimental conditions.

PMID- 16801387
TI  - Numerical simulation of a Campbell-like stochastic delay model for bacteriophage
      infection.
AB  - In this work, we consider a delay differential equations model for bacteriophage
      infection and discuss the robustness of the positive equilibrium with respect to
      stochastic perturbations of the environment using two different approaches.
      First, we provide analytical estimates of the population intensities of
      fluctuations by Fourier transform methods. Next, we simulate the strong solutions
      of the arising stochastic delay differential equations by numerical methods of
      order 1. Extensive numerical experiments suggest that a noisy environment for the
      bacteria population is much more destabilizing on the concentrations at the
      equilibrium point than a noisy environment for the phage.

PMID- 16801386
TI  - Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
AB  - Ion channels are membrane-spanning proteins that allow ions to permeate at high
      rates. The kinetic characteristics of the channels present in a cell determine
      the cell signaling profile and therefore cell function in many different
      physiological processes. We found that Kv1.7 channels from mouse heart muscle
      have two putative translation initiation start sites that generate two channel
      isoforms with different functional characteristics, mKv1.7L (489 aa) and a
      shorter mKv1.7S (457 aa). The electrophysiological analysis of mKv1.7L and
      mKv1.7S channels revealed that the two channel isoforms have different
      inactivation kinetics. The channel resulting from the longer protein (L)
      inactivates faster than the shorter channels (S). Our data supports the
      hypothesis that mKv1.7L channels inactivate predominantly due to an N-type
      related mechanism, which is impaired in the mKv1.7S form. Furthermore, only the
      longer version mKv1.7L is regulated by the cell redox state, whereas the shorter
      form mKv1.7S is not. Thus, expression starting at each translation initiation
      site results in significant functional divergence. Our data suggest that the
      redox modulation of mKv1.7L may occur through a site in the cytoplasmic N
      terminal domain that seems to encompass a metal coordination motif resembling
      those found in many redox-sensitive proteins. The mRNA expression profile and
      redox modulation of mKv1.7 kinetics identify these channels as molecular entities
      of potential importance in cellular redox-stress states such as hypoxia.

PMID- 16801388
TI  - Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase-mediated apoptosis of HeLa
      cells.
AB  - We show that caspase-3 cleaves Cdc6 at D(290)/S and D(442)/G sites, producing p32
      tCdc6 (truncated Cdc6) and p49-tCdc6, respectively, during etoposide- or tumor
      necrosis factor (TNF)-alpha-induced apoptosis. The expression of these tCdc6
      proteins, p32- and p49-tCdc6, promotes etoposide-induced apoptosis. The
      expression of tCdc6 perturbs the loading of Mcm2 but not Orc2 onto chromatin and
      activates ataxia telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR)
      kinase activities with kinetics similar to that of the phosphorylation of Chk1/2.
      The activation kinetics are consistent with elevated cellular levels of p53 and
      mitochondrial levels of Bax. The tCdc6-induced effects are all suppressed to
      control levels by expressing a Cdc6 mutant that cannot be cleaved by caspase-3
      (Cdc6-UM). Cdc6-UM expression attenuates the TNF-alpha-induced activation of ATM
      and caspase-3 activities. When ATM or ATR is down-expressed by using the small
      interfering RNA technique, the TNF-alpha- or tCdc6-induced activation of caspase
      3 activities is suppressed in the cells. These results suggest that tCdc6
      proteins act as dominant-negative inhibitors of replication initiation and that
      they disrupt chromatin structure and/or induce DNA damage, leading to the
      activation of ATM/ATR kinase activation and p53-Bax-mediated apoptosis.

PMID- 16801389
TI  - Interneurite affinity is regulated by heterophilic nectin interactions in concert
      with the cadherin machinery.
AB  - Neurites recognize their specific partners during the formation of interneuronal
      connections. In hippocampal pyramidal neurons, axons attach to dendrites for
      their synaptogenesis, but the dendrites do not form stable contacts with each
      other, suggesting the presence of a mechanism to allow their selective
      associations. Nectin-1 (N1), an immunoglobulin domain adhesive protein, is
      preferentially localized in axons, and its heterophilic partner, N3, is present
      in both axons and dendrites; we tested their potential roles in interneurite
      recognition. The overexpression of N1, causing its mislocalization to dendrites,
      induced atypical dendrodendritic as well as excessive axodendritic associations.
      On the contrary, the genetic deletion of N1 loosened the contacts between axons
      and dendritic spines. Those actions of nectins required cadherin-catenin
      activities, but the overexpression of cadherin itself could not accelerate
      neurite attachment. These results suggest that the axon-biased localization of N1
      and its trans-interaction with N3 in cooperation with the cadherin machinery is
      critical for the ordered association of axons and dendrites.

PMID- 16801391
TI  - Peroxisome biogenesis: the peroxisomal endomembrane system and the role of the
      ER.
AB  - Peroxisomes have long been viewed as semiautonomous, static, and homogenous
      organelles that exist outside the secretory and endocytic pathways of vesicular
      flow. However, growing evidence supports the view that peroxisomes actually
      constitute a dynamic endomembrane system that originates from the endoplasmic
      reticulum. This review highlights the various strategies used by evolutionarily
      diverse organisms for coordinating the flow of membrane-enclosed carriers through
      the peroxisomal endomembrane system and critically evaluates the dynamics and
      molecular mechanisms of this multistep process.

PMID- 16801390
TI  - Microclusters of inhibitory killer immunoglobulin-like receptor signaling at
      natural killer cell immunological synapses.
AB  - We report the supramolecular organization of killer Ig-like receptor (KIR)
      phosphorylation using a technique applicable to imaging phosphorylation of any
      green fluorescent protein-tagged receptor at an intercellular contact or immune
      synapse. Specifically, we use fluorescence lifetime imaging (FLIM) to report
      Forster resonance energy transfer (FRET) between GFP-tagged KIR2DL1 and a Cy3
      tagged generic anti-phosphotyrosine monoclonal antibody. Visualization of KIR
      phosphorylation in natural killer (NK) cells contacting target cells expressing
      cognate major histocompatibility complex class I proteins revealed that
      inhibitory signaling is spatially restricted to the immune synapse. This explains
      how NK cells respond appropriately when simultaneously surveying susceptible and
      resistant target cells. More surprising, phosphorylated KIR was confined to
      microclusters within the aggregate of KIR, contrary to an expected homogeneous
      distribution of KIR signaling across the immune synapse. Also, yellow fluorescent
      protein-tagged Lck, a kinase important for KIR phosphorylation, accumulated in a
      multifocal distribution at inhibitory synapses. Spatial confinement of receptor
      phosphorylation within the immune synapse may be critical to how activating and
      inhibitory signals are integrated in NK cells.

PMID- 16801392
TI  - Disposable colorimetric carbon dioxide detector use as an indicator of a patent
      airway during noninvasive mask ventilation.
AB  - Colorimetric carbon dioxide detectors are useful indicators of proper
      endotracheal tube placement. We have found that they also are helpful during bag
      and mask ventilation as an indicator of a patent airway. In this report, we
      describe our experience with these devices for use during preintubation airway
      stabilization as observed during videotaped performances from a prospective,
      randomized trial of intubation premedication.

PMID- 16801393
TI  - Multidisciplinary surgical approach to a surviving infant with sirenomelia.
AB  - Sirenomelia is an extremely complex and rare malformation with different degrees
      of lower-extremities fusion associated with gastrointestinal, musculoskeletal,
      vascular, cardiopulmonary, and central nervous system malformations. In the
      English literature, there are only 5 reports of infants surviving with this
      condition. In our case, a 2540-g female infant was born with normal vital signs,
      no facial dysmorphism, and a complete soft tissue fusion of the lower limbs, from
      perineum to ankles. Radiologic examinations revealed an intestinal atresia and a
      single pelvic kidney, with a unique ureter, 2 femurs, 2 tibias, 2 fibulas, and 2
      feet (simpus dipus). At 7 months of age, a multidisciplinary surgical team
      achieved complete separation of the lower limbs, with independent vascular and
      nerve supplies. At the time of this writing, the infant was 28 months old and had
      a regular growth curve. Many future reconstructive surgeries have been planned to
      achieve an acceptable quality of life for this infant.

PMID- 16801394
TI  - Spontaneous tracheal rupture after severe coughing in a 7-year-old boy.
AB  - Tracheal lacerations are rare but potentially life-threatening. They are
      recognized sequelae of cervical or thoracic injuries or complications of
      endotracheal intubation. Spontaneous tracheal rupture is extremely uncommon and
      has not been reported in a pediatric patient. This report is the first pediatric
      case of a spontaneous longitudinal laceration of the posterior membranous
      cervical trachea, which occurred after violent coughing in a 7-year-old boy with
      acute tracheobronchitis. The tracheal rupture was detected early with an
      endoscopic examination and computed tomography. The rupture and emphysema were
      small, with no major complications, and disappeared with conservative management.
      This rare case is presented with a review of the possible mechanism, diagnosis,
      and treatment.

PMID- 16801395
TI  - Evidence that the root of the tree of life is not within the Archaea.
AB  - The Archaea occupy uncommon and extreme habitats around the world. They
      manufacture unusual compounds, utilize novel metabolic pathways, and contain many
      unique genes. Many suspect, due to their novel properties, that the root of the
      tree of life may be within the Archaea, although there is little direct evidence
      for this root. Here, using gene insertions and deletions found within protein
      synthesis factors present in all prokaryotes and eukaryotes, we present
      statistically significant evidence that the root of life is outside the Archaea.

PMID- 16801396
TI  - Comparison of polyethylene glycol-conjugated recombinant human
      acetylcholinesterase and serum human butyrylcholinesterase as bioscavengers of
      organophosphate compounds.
AB  - Comparative protection studies in mice demonstrate that on a molar basis,
      recombinant human acetylcholinesterase (rHuAChE) confers higher levels of
      protection than native human butyrylcholinesterase (HuBChE) against
      organophosphate (OP) compound intoxication. For example, mice challenged with 2.5
      LD50 of O-isopropyl methylphosphonofluoridate (sarin), pinacolylmethyl
      phosphonofluoridate (soman), and O-ethyl-S-(2-isopropylaminoethyl)
      methylphosphonothiolate (VX) after treatment with equimolar amounts of the two
      cholinesterases displayed 80, 100, and 100% survival, respectively, when pre
      treatment was carried out with rHuAChE and 0, 20, and 60% survival, respectively,
      when pretreatment was carried out with HuBChE. Kinetic studies and active site
      titration analyses of the tested OP compounds with acetylcholinesterases (AChEs)
      and butyrylcholinesterases (BChEs) from different mammalian species demonstrate
      that the superior in vivo efficacy of acetyl-cholinesterases is in accordance
      with the higher stereoselectivity of AChE versus BChE toward the toxic
      enantiomers comprising the racemic mixtures of the various OP agents. In
      addition, we show that polyethylene glycol-conjugated (PEGy-lated) rHuAChE, which
      is characterized by a significantly extended circulatory residence both in mice
      and monkeys ( Biochem J 357: 795-802, 2001 ; Biochem J 378: 117-128, 2004 ),
      retains full reactivity toward OP compounds both in vitro and in vivo and
      provides a higher level of protection to mice against OP poisoning, compared with
      native serum-derived HuBChE. Indeed, PEGylated rHuAChE also confers superior
      prophylactic protection when administered intravenously or intramuscularly over
      20 h before exposure of mice to a lethal dose of VX (1.3-1.5 LD50). These
      findings together with the observations that the PEGylated rHuAChE exhibits
      unaltered biodistribution and high bioavailability present a case for using
      PEGylated rHuAChE as a very efficacious bioscavenger of OP agents.

PMID- 16801397
TI  - The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human
      melanoma cells.
AB  - The mitogen-activated protein kinase (MAPK) pathway is frequently activated in
      human cancers, leading to malignant phenotypes such as autonomous cellular
      proliferation. Here, we demonstrate a novel role of the activated MAPK pathway in
      immune evasion by melanoma cells with the mutation of BRAF, which encodes a
      MAPKKs, (BRAF(V600E)). MEK inhibitor U0126 or RNA interference (RNAi) for
      BRAF(V600E) decreased production of the immunosuppressive soluble factors
      interleukin (IL)-10, VEGF, or IL-6 from melanoma cells to levels comparable to
      those after signal transducer and activator of transcription (STAT)3
      inactivation. The suppressive activity of the culture supernatants from the
      melanoma cells on the production of inflammatory cytokines IL-12 and tumor
      necrosis factor alpha by dendritic cells upon lipopolysaccharide stimulation was
      markedly reduced after transduction with BRAF(V600E) RNAi, comparable to the
      effects observed with STAT3 RNAi transduction. No additive or synergistic effects
      were observed by the simultaneous transduction of RNAi for both BRAF(V600E) and
      STAT3. Furthermore, specific DNA binding and transcriptional activity of STAT3
      were not affected by down-regulation of the MAPK signaling with the BRAF RNAi.
      These results indicate that the MAPK signal, along with the STAT3 signal, is
      essential for immune evasion by human melanomas that have constitutively active
      MAPK signaling and is a potential molecular target for overcoming melanoma cell
      evasion of the immune system.

PMID- 16801398
TI  - Light chain editing generates polyreactive antibodies in chronic graft-versus
      host reaction.
AB  - The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused
      by alloreactive CD4(+) T cells from a Bm-12 mouse in a C57BL/6 recipient. We used
      this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to
      understand the structure, specificity, and origin of the induced autoantibodies
      (auto-Abs). We found anti-DNA Abs that reacted to several different antigens,
      such as phosphatidylserine, myelin basic protein, thyroglobulin, histone,
      insulin, cytochrome C, and beta-galactosidase. This polyreactivity was found for
      Abs from B cells that expressed the 56R H chain transgene with "editor" L chains
      that did not completely veto autoreactivity. We suggest that such incomplete
      editing results in polyreactivity and that incompletely edited polyreactive B
      cells influence the subsequent expression of pathogenic auto-Abs in disease. We
      also found B cells that coexpress kappa and lambda L chain. These B cells
      contributed to the autoimmune response and are possibly in the marginal zone of
      the spleen.

PMID- 16801399
TI  - An autosomal dominant major gene confers predisposition to pulmonary tuberculosis
      in adults.
AB  - The molecular basis of genetic predisposition to pulmonary tuberculosis in adults
      remains largely elusive. Few candidate genes have consistently been implicated in
      tuberculosis susceptibility, and no conclusive linkage was found in two previous
      genome-wide screens. We report here a genome-wide linkage study in a total sample
      of 96 Moroccan multiplex families, including 227 siblings with microbiologically
      and radiologically proven pulmonary tuberculosis. A genome-wide scan conducted in
      half the sample (48 families) identified five regions providing suggestive
      evidence (logarithm of the odds [LOD] score >1.17; P < 0.01) for linkage. These
      regions were then fine-mapped in the total sample of 96 families. A single region
      of chromosome 8q12-q13 was significantly linked to tuberculosis (LOD score =
      3.49; P = 3 x 10(-5)), indicating the presence of a major tuberculosis
      susceptibility gene. Linkage was stronger (LOD score = 3.94; P = 10(-5)) in the
      subsample of 39 families in which one parent was also affected by tuberculosis,
      whereas it was much lower (LOD score = 0.79) in the 57 remaining families without
      affected parents, supporting a dominant mode of inheritance of the major
      susceptibility locus. These results provide direct molecular evidence that human
      pulmonary tuberculosis has a strong genetic basis, and indicate that the genetic
      component involves at least one major locus with a dominant susceptibility
      allele.

PMID- 16801400
TI  - FOXO3a-dependent regulation of Puma in response to cytokine/growth factor
      withdrawal.
AB  - Puma is an essential mediator of p53-dependent and -independent apoptosis in
      vivo. In response to genotoxic stress, Puma is induced in a p53-dependent manner.
      However, the transcription factor driving Puma up-regulation in response to p53
      independent apoptotic stimuli has yet to be identified. Here, we show that FOXO3a
      up-regulates Puma expression in response to cytokine or growth factor
      deprivation. Importantly, dysregulated Akt signaling in lymphoid cells attenuated
      Puma induction upon cytokine withdrawal. Our results suggest that Puma, together
      with another BH3 only member, Bim, function as FOXO3a downstream targets to
      mediate a stress response when PI3K/Akt signaling is down-regulated.

PMID- 16801401
TI  - Essential role of membrane cholesterol in accelerated BCR internalization and
      uncoupling from NF-kappa B in B cell clonal anergy.
AB  - Divergent hypotheses exist to explain how signaling by the B cell receptor (BCR)
      is initiated after antigen binding and how it is qualitatively altered in anergic
      B cells to selectively uncouple from nuclear factor kappaB and c-Jun N-terminal
      kinase pathways while continuing to activate extracellular signal-regulated
      kinase and calcium-nuclear factor of activated T cell pathways. Here we find that
      BCRs on anergic cells are endocytosed at a very enhanced rate upon binding
      antigen, resulting in a large steady-state pool of intracellularly sequestered
      receptors that appear to be continuously cycling between surface and
      intracellular compartments. This endocytic mechanism is exquisitely sensitive to
      the lowering of plasma membrane cholesterol by methyl-beta-cyclodextrin, and,
      when blocked in this way, the sequestered BCRs return to the cell surface and
      RelA nuclear accumulation is stimulated. In contrast, when plasma membrane
      cholesterol is lowered and GM1 sphingolipid markers of membrane rafts are
      depleted in naive B cells, this does not diminish BCR signaling to calcium or
      RelA. These results provide a possible explanation for the signaling changes in
      clonal anergy and indicate that a chief function of membrane cholesterol in B
      cells is not to initiate BCR signaling, but instead to terminate a subset of
      signals by rapid receptor internalization.

PMID- 16801402
TI  - Population pharmacokinetic assessment of a new regimen of mefloquine used in
      combination treatment of uncomplicated falciparum malaria.
AB  - A fixed artesunate-mefloquine combination, comprising three daily doses of 8 mg
      of mefloquine/kg of body weight and 4 mg of artesunate/kg, has been developed
      recently. This study was designed to construct a population pharmacokinetic model
      describing this new dosage regimen of mefloquine given as loose tablets together
      with artesunate. In two randomized trials in Thailand which evaluated the
      efficacy, safety, and tolerability of this new regimen, the members of a subgroup
      of 50 patients were randomized to have capillary blood sampling before treatment
      and at five randomly assigned time points during the 63-day follow-up period.
      Mefloquine levels in capillary whole blood were assayed by liquid chromatography
      with UV detection. A pharmacokinetic model for mefloquine was constructed using
      mixed-effects modeling. A one-compartment model with first-order absorption and
      elimination was selected to describe the kinetic properties of mefloquine. For
      capillary whole-blood mefloquine, the area under the concentration curve (AUC)
      was 40% higher than previous estimates for patients given the equivalent
      conventional-dose regimen (mefloquine given as 15 mg/kg and then 10 mg/kg on the
      second and third days of treatment). The half-life (t1/2) of the carboxylic acid
      metabolite was estimated as 26 days, and the metabolite was eliminated more
      slowly than the parent drug (population t1/2 estimate, 10.5 days). Splitting the
      25 mg/kg dose of mefloquine into three doses of 8 mg/kg each resulted in improved
      oral bioavailability compared to the conventional split-dose regimen results.
      This new regimen is well tolerated and results in an equivalent therapeutic
      response.

PMID- 16801403
TI  - Antimicrobial activity and spectrum of cefovecin, a new extended- spectrum
      cephalosporin, against pathogens collected from dogs and cats in Europe and North
      America.
AB  - Cefovecin is a new extended-spectrum semisynthetic cephalosporin indicated for
      the treatment of bacterial infections in dogs and cats. This study evaluated the
      in vitro activity and spectrum of cefovecin against 2,641 recent clinical
      isolates (1,660 canine and 981 feline isolates) from Europe and the United
      States. MIC determinations against cefovecin and other reference antimicrobials
      were performed by broth microdilution methods recommended by the Clinical and
      Laboratory Standards Institute (CLSI, formerly NCCLS). Cefovecin demonstrated
      bactericidal activity against both gram-positive and gram-negative pathogens.
      Cefovecin exhibited in vitro activity against all major aerobic and anaerobic
      bacterial pathogens associated with skin, urinary tract, and periodontal
      infections in dogs and cats. The MIC90 values of cefovecin against Staphylococcus
      intermedius, Escherichia coli, and Pasteurella multocida were 0.25 microg/ml, 1.0
      microg/ml, and 0.06 microg/ml, respectively. No significant differences were
      observed in terms of the activities of cefovecin against pathogens from different
      European countries and against pathogens of European and U.S. origin.

PMID- 16801404
TI  - Absence of cochleotoxicity measured by standard and high-frequency pure tone
      audiometry in a trial of once- versus three-times-daily tobramycin in cystic
      fibrosis patients.
AB  - We undertook assessment of hearing in patients with cystic fibrosis who were
      taking part in a large randomized controlled trial of once- versus three-times
      daily tobramycin for pulmonary exacerbations of cystic fibrosis (the TOPIC
      study). All patients were eligible to have standard pure tone audiometry
      performed across the frequency range of 0.25 to 8 kHz. High-frequency pure tone
      audiometry over 10 to 16 kHz was also performed with a subset of patients.
      Audiometry was undertaken at the start of tobramycin treatment, at the end of a
      14-day course of treatment, and at follow-up 6 to 8 weeks later. We enrolled 244
      patients, of whom 219 (125 children and 94 adults) completed treatment. Nineteen
      patients were excluded from analysis due to abnormal baseline audiometry.
      Complete pre- and posttreatment standard audiological data were obtained for
      168/219 patients. We found no significant differences in hearing thresholds when
      they were assessed at the baseline, at the end of treatment, and at follow-up 6
      to 8 weeks later were compared. In addition, no significant differences in
      hearing thresholds were detected between treatment regimens. Similar results were
      obtained for the subset of 63/168 patients who underwent high-frequency
      audiometry. We conclude that for a single 14-day course of tobramycin treatment
      in patients with cystic fibrosis with no preexisiting auditory deficit, no
      measurable effect on hearing was apparent with either once- or three-times-daily
      treatment. Estimation of the cumulative cochleotoxic risk in cystic fibrosis
      patients due to repeated aminoglycoside therapy, as evidenced by the patients
      excluded from this study due to hearing loss, also requires further
      characterization.

PMID- 16801405
TI  - Multiple cis-acting sequences mediate upregulation of the MDR1 efflux pump in a
      fluconazole-resistant clinical Candida albicans isolate.
AB  - Overexpression of the MDR1 gene, which encodes a multidrug efflux pump of the
      major facilitator superfamily, is a frequent cause of resistance to the
      antimycotic agent fluconazole and other metabolic inhibitors in clinical Candida
      albicans strains. Constitutive MDR1 overexpression in such strains is caused by
      mutations in as yet unknown trans-regulatory factors. In order to identify the
      cis-acting sequences in the MDR1 regulatory region that mediate constitutive MDR1
      upregulation, we performed a promoter deletion analysis in the genetic background
      of an MDR1-overexpressing clinical C. albicans isolate. We found that several
      different regions in the MDR1 promoter can mediate MDR1 overexpression in this
      isolate. In contrast, deletion of one of these regions abolished benomyl-induced
      MDR1 expression in a C. albicans laboratory strain. These results suggest that
      multiple transcription factors control expression of the MDR1 efflux pump in C.
      albicans and that the mutation(s) that causes constitutive MDR1 overexpression
      and drug resistance in clinical C. albicans isolates affects the activities of
      several of these transcription factors.

PMID- 16801406
TI  - Pharmacokinetics of telbivudine in healthy subjects and absence of drug
      interaction with lamivudine or adefovir dipivoxil.
AB  - Two phase I studies were conducted to assess the plasma pharmacokinetics of
      telbivudine and potential drug-drug interactions between telbivudine (200 or 600
      mg/day) and lamivudine (100 mg/day) or adefovir dipivoxil (10 mg/day) in healthy
      subjects. Study drugs were administered orally. The pharmacokinetics of
      telbivudine were characterized by rapid absorption with biphasic disposition. The
      maximum concentrations in plasma (Cmax) were reached at median times ranging from
      2.5 to 3.0 h after dosing. Mean single-dose Cmax and area under the plasma
      concentration-time curve from time zero to infinity (AUC0-infinity) were 1.1 and
      2.9 microg/ml and 7.4 and 21.8 microg . h/ml for the 200- and 600-mg telbivudine
      doses, respectively. Steady state was reached after daily dosing for 5 to 7 days.
      The mean steady-state Cmax and area under the plasma concentration-time curve
      over the dosing interval (AUCtau) were 1.2 and 3.4 microg/ml and 8.9 and 27.5
      microg . h/ml for the 200- and 600-mg telbivudine repeat doses, respectively. The
      steady-state AUCtau of telbivudine was 23 to 57% higher than the single-dose
      values. Concomitant lamivudine or adefovir dipivoxil did not appear to
      significantly alter the steady-state plasma pharmacokinetics of telbivudine; the
      geometric mean ratios and associated 90% confidence interval (CI) for the AUCtau
      of telbivudine alone versus in combination were 106.3% (92.0 to 122.8%) and 98.6%
      (86.4 to 112.5%) when coadministered with lamivudine and adefovir dipivoxil,
      respectively. Similarly, the steady-state plasma pharmacokinetics of lamivudine
      or adefovir were not markedly affected by the coadministration of telbivudine;
      the geometric mean ratios and associated 90% CI, alone versus in combination with
      telbivudine, were 99.0% (87.1 to 112.4%) and 92.2% (84.0 to 101.1%),
      respectively, for the lamivudine and adefovir AUCtau values. Moreover, the
      combination regimens studied were well tolerated in all subjects. The results
      from these studies provide pharmacologic support for combination therapy or
      therapy switching involving telbivudine, lamivudine, and adefovir dipivoxil for
      the treatment of chronic hepatitis B virus infection.

PMID- 16801407
TI  - Proteolytic degradation of human antimicrobial peptide LL-37 by Bacillus
      anthracis may contribute to virulence.
AB  - In this paper we report on the susceptibilities of a range of Bacillus species to
      the human antimicrobial peptide LL-37. B. subtilis showed a low level of
      resistance to killing by LL-37 (50% growth-inhibitory concentration [GI50], 1
      microg/ml). B. cereus and B. thuringiensis showed intermediate levels of
      resistance to killing (GI50s, 33 microg/ml and 37 microg/ml, respectively). B.
      anthracis showed the highest level of resistance (GI50s, 40 to 66 microg/ml). The
      degradation of LL-37 by B. anthracis culture supernatant was blocked by the
      metalloprotease inhibitors EDTA and 1,10-phenanthroline, and the gene encoding
      the protease responsible for LL-37 degradation was not plasmid borne. Our
      findings suggest that alongside the classical plasmid-based virulence
      determinants, extracellular metalloproteases of B. anthracis may play a role in
      survival in the host.

PMID- 16801408
TI  - Activity of LBM415 compared to those of 11 other agents against Haemophilus
      species.
AB  - When tested against 254 Haemophilus influenzae strains, LBM415, a peptide
      deformylase inhibitor, gave MIC50 and MIC90 values of 2.0 microg/ml and 8.0
      microg/ml, respectively. The MICs were independent of beta-lactam or quinolone
      susceptibility and the presence or absence of macrolide efflux or ribosomal
      protein mutations. The MICs of LBM415 against 23 H. parainfluenzae strains were
      similar to those against H. influenzae. In contrast, erythromycin, azithromycin,
      and clarithromycin gave unimodal MIC distributions, and apart from beta-lactamase
      negative, ampicillin-resistant strains, all strains were susceptible to the beta
      lactams tested. Apart from selected quinolone-resistant strains, all strains were
      susceptible to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and
      gemifloxacin. Resistance to trimethoprim-sulfamethoxazole was common. The
      potencies of all drugs against 23 H. parainfluenzae strains were similar to those
      against H. influenzae. Time-kill studies with 10 Haemophilus strains showed
      LBM415 to be bactericidal at 2 x the MIC against 8 of 10 strains after 24 h. For
      comparison, the macrolides and beta-lactams were bactericidal against 8 to 10
      strains each at 2 x the MIC after 24 h. Quinolones were bactericidal against all
      10 strains tested at 2 x the MIC after 24 h. Against six H. influenzae strains,
      postantibiotic effects for LBM415 lasted between 0.8 and 2.2 h. In multistep
      resistance selection studies, LBM415 produced resistant clones in 7 of the 10
      strains tested, with MICs ranging from 4 to 64 microg/ml. No mutations in
      deformylase (def) and formyltransferase (fmt) genes were detected in any of the
      LBM415-resistant mutants.

PMID- 16801409
TI  - Daptomycin bactericidal activity and correlation between disk and broth
      microdilution method results in testing of Staphylococcus aureus strains with
      decreased susceptibility to vancomycin.
AB  - A total of 207 Staphylococcus aureus strains, including 105 well-characterized
      strains with decreased susceptibility to vancomycin (17 vancomycin-intermediate
      S. aureus [VISA] and 88 heteroresistant VISA [hVISA] strains) and 102 wild-type
      methicillin-resistant S. aureus (MRSA-WT) strains were tested by
      reference/standardized broth microdilution and disk diffusion methods, as well as
      by Etest (AB BIODISK, Solna, Sweden), against daptomycin and vancomycin. The
      lowest concentration of antimicrobial agent that killed > or = 99.9% of the
      initial inoculum was defined as the minimum bactericidal concentration (MBC)
      endpoint, and time-kill curves were performed in selected strains to further
      evaluate bactericidal activity. All MRSA-WT and hVISA strains were inhibited by <
      or = 1 microg/ml of daptomycin, while the VISA strains showed slightly higher
      daptomycin MICs (range, 0.5 to 4 microg/ml). All daptomycin MBC results were at
      the MIC or twofold higher. In contrast, 14.7% of MRSA-WT, 69.3% of hVISA, and all
      VISA strains showed a vancomycin MBC/MIC ratio of > or = 32 or an MBC of > or =
      16 microg/ml (tolerant). The correlation coefficients between broth microdilution
      and disk diffusion method results were low for daptomycin (0.07) and vancomycin
      (0.11). Eight (3.8%) strains (all hVISA or VISA) were "nonsusceptible" to
      daptomycin by broth microdilution methods but susceptible by the disk diffusion
      method. For vancomycin, 35 (16.9%) strains were nonsusceptible by broth
      microdilution methods but susceptible by disk diffusion methods. In conclusion,
      daptomycin was highly bactericidal against S. aureus strains, and its
      bactericidal activity was not affected by decreased susceptibility to vancomycin.
      In contrast, many (one in seven) contemporary MRSA-WT, the majority of hVISA, and
      all VISA strains showed vancomycin MBC/MIC ratios consistent with tolerance, a
      predictor of poor clinical response. Disk diffusion tests generally failed to
      detect strains categorized as nonsusceptible to daptomycin or vancomycin by the
      reference broth microdilution method or Etest, and reassessment of breakpoints
      should be immediately attempted for MIC methods suggested as the test of choice.

PMID- 16801410
TI  - In vitro selection and in vivo efficacy of piperazine- and alkanediamide-linked
      bisbenzamidines against Pneumocystis pneumonia in mice.
AB  - Bisbenzamidines, such as pentamidine isethionate, are aromatic dicationic
      compounds that are active against Pneumocystis and other microbes but are
      oftentimes toxic to the host. To identify potential anti-Pneumocystis agents, we
      synthesized bisbenzamidine derivatives in which the parent compound pentamidine
      was modified by a 1,4-piperazinediyl, alkanediamide, or 1,3-phenylenediamide
      moiety as the central linker. Several of the compounds were more active against
      P. carinii and less toxic than pentamidine in cytotoxicity assays. For this
      study, we evaluated nine bisbenzamidine derivatives representing a range of in
      vitro activities, from highly active to inactive, for the treatment of
      pneumocystosis in an immunosuppressed mouse model. Six of these in vitro-active
      compounds, 01, 02, 04, 06, 100, and 101, exhibited marked efficacies against
      infection at a dose of 10 mg/kg of body weight, and four compounds, 01, 04, 100,
      and 101, showed significant increases in survival versus that of untreated
      infected control mice. Compound 100 was highly efficacious against the infection
      at 20 mg/kg and 40 mg/kg, with > 1,000-fold reductions in burden, and resulted in
      improved survival curves versus those for pentamidine-treated mice (at the same
      doses). All six bisbenzamidine compounds that exhibited high in vitro activity
      significantly decreased the infection in vivo; two compounds, 12 and 102, with
      marked to moderate in vitro activities had slight or no activity in vivo, while
      compound 31 was inactive in vitro and was also inactive in vivo. Thus, the
      selection of highly active compounds from in vitro cytotoxicity assays was
      predictive of activity in the mouse model of Pneumocystis pneumonia. We conclude
      that a number of these bisbenzamidine compounds, especially compound 100, may
      show promise as new anti-Pneumocystis drugs.

PMID- 16801411
TI  - Use of probabilistic modeling within a physiologically based pharmacokinetic
      model to predict sulfamethazine residue withdrawal times in edible tissues in
      swine.
AB  - The presence of antimicrobial agents in edible tissues of food-producing animals
      remains a major public health concern. Probabilistic modeling techniques
      incorporated into a physiologically based pharmacokinetic (PBPK) model were used
      to predict the amounts of sulfamethazine residues in edible tissues in swine. A
      PBPK model for sulfamethazine in swine was adapted to include an oral dosing
      route. The distributions for sensitive parameters were determined and were used
      in a Monte Carlo analysis to predict tissue residue times. Validation of the
      distributions was done by comparison of the results of a Monte Carlo analysis to
      those obtained with an external data set from the literature and an in vivo pilot
      study. The model was used to predict the upper limit of the 95% confidence
      interval of the 99th percentile of the population, as recommended by the U.S.
      Food and Drug Administration (FDA). The external data set was used to calculate
      the withdrawal time by using the tolerance limit algorithm designed by FDA. The
      withdrawal times obtained by both methods were compared to the labeled withdrawal
      time for the same dose. The Monte Carlo method predicted a withdrawal time of 21
      days, based on the amounts of residues in the kidneys. The tolerance limit method
      applied to the time-limited data set predicted a withdrawal time of 12 days. The
      existing FDA label withdrawal time is 15 days. PBPK models can incorporate
      probabilistic modeling techniques that make them useful for prediction of tissue
      residue times. These models can be used to calculate the parameters required by
      FDA and explore those conditions where the established withdrawal time may not be
      sufficient.

PMID- 16801412
TI  - In vivo survival of teicoplanin-resistant Staphylococcus aureus and fitness cost
      of teicoplanin resistance.
AB  - Glycopeptide resistance, in a set of in vitro step-selected teicoplanin-resistant
      mutants derived from susceptible Staphylococcus aureus SA113, was associated with
      slower growth, thickening of the bacterial cell wall, increased N
      acetylglucosamine incorporation, and decreased hemolysis. Differential
      transcriptome analysis showed that as resistance increased, some virulence
      associated genes became downregulated. In a mouse tissue cage infection model, an
      inoculum of 10(4) CFU of strain SA113 rapidly produced a high-bacterial-load
      infection, which triggered MIP-2 release, leukocyte infiltration, and reduced
      leukocyte viability. In contrast, with the same inoculum of the isogenic
      glycopeptide-resistant derivative NM67, CFU initially decreased, resulting in the
      elimination of the mutant in three out of seven cages. In the four cages in which
      NM67 survived, it partially regained wild-type characteristics, including
      thinning of the cell wall, reduced N-acetylglucosamine uptake, and increased
      hemolysis; however, the survivors also became teicoplanin hypersusceptible. The
      elimination of the teicoplanin-resistant mutants and selection of teicoplanin
      hypersusceptible survivors in the tissue cages indicated that glycopeptide
      resistance imposes a fitness burden on S. aureus and is selected against in vivo,
      with restoration of fitness incurring the price of resistance loss.

PMID- 16801413
TI  - Quinolones sensitize gram-negative bacteria to antimicrobial peptides.
AB  - The treatment of infections caused by bacteria resistant to the vast majority of
      antibiotics is a challenge worldwide. Antimicrobial peptides (APs) make up the
      front line of defense in those areas exposed to microorganisms, and there is
      intensive research to explore their use as new antibacterial agents. On the other
      hand, it is known that subinhibitory concentrations of antibiotics affect the
      expression of numerous bacterial traits. In this work we evaluated whether
      treatment of bacteria with subinhibitory concentrations of quinolones may alter
      the sensitivity to APs. A 1-h treatment of Klebsiella pneumoniae with 0.25 x the
      MIC of ciprofloxacin rendered bacteria more sensitive to polymyxins B and E,
      human neutrophil defensin 1, and beta-defensin 1. Levofloxacin and nalidixic acid
      at 0.25 x the MICs also increased the sensitivity of K. pneumoniae to polymyxin
      B, whereas gentamicin and ceftazidime at 0.25 x the MICs did not have such an
      effect. Ciprofloxacin also increased the sensitivities of K. pneumoniae
      ciprofloxacin-resistant strains to polymyxin B. Two other pathogens, Pseudomonas
      aeruginosa and Haemophilus influenzae, also became more sensitive to polymyxins B
      and E after treatment with 0.25 x the MIC of ciprofloxacin. Incubation with
      ciprofloxacin did not alter the expression of the K. pneumoniae loci involved in
      resistance to APs. A 1-N-phenyl-naphthylamine assay showed that ciprofloxacin and
      levofloxacin increased the permeabilities of the K. pneumoniae and P. aeruginosa
      outer membranes, while divalent cations antagonized this action. Finally, we
      demonstrated that ciprofloxacin and levofloxacin increased the binding of APs to
      the outer membrane by using dansylated polymyxin B.

PMID- 16801414
TI  - Absorption, metabolism, and excretion of [14C]viramidine in humans.
AB  - Absorption, metabolism, and excretion of [14C]viramidine, a prodrug of ribavirin,
      were studied in humans following a single oral dose (600 mg). Viramidine was
      rapidly absorbed, with a time to maximum concentration of the drug in plasma of
      1.5 h. Viramidine and ribavirin accounted for only 4.3% and 42% of plasma area
      under the concentration-time curve (AUC) for radioactivity, respectively,
      indicating extensive conversion of viramidine to ribavirin, followed by further
      metabolism of ribavirin. The drug was largely trapped in red blood cells (RBC),
      with an RBC-to-plasma radioactivity AUC0-infinity ratio of 108. Excretion of
      total radioactivity in urine and feces accounted for 50.8% and 26.1% of the dose,
      respectively. The metabolic profile in urine (0 to 24 h) indicated that
      viramidine was excreted primarily as triazole carboxamide (TCONH2), triazole
      carboxylic acid nucleoside (TCOOH), and ribavirin with a small amount of
      unchanged viramidine, which each accounted for 64.1%, 17.0%, 15.7%, and 3.2% of
      urinary radioactivity, respectively. The amounts of unchanged viramidine (3.4% of
      dose) and ribavirin (10% of dose) in urine were small after oral administration
      of viramidine.

PMID- 16801415
TI  - Impact of antimicrobial dosing regimen on evolution of drug resistance in vivo:
      fluconazole and Candida albicans.
AB  - Numerous factors have been theorized to affect the development of antimicrobial
      resistance, including those specific to the host, the organism, the environment,
      the drug, and the drug prescriber. One variable under the control of the
      prescriber is the drug dosing regimen. Dosing regimens can vary in dose level,
      dosing interval, and treatment duration. The current studies examined the
      relationships between antimicrobial dosing regimens and resistance development by
      use of an in vivo model. A murine model of systemic Candida albicans infection
      was used to examine resistance emergence during exposure to the triazole
      antifungal fluconazole. Data from this experimental model demonstrated that the
      more frequently administered dosing prevented selection of the isogenic resistant
      cell populations. Conversely, dosing regimens producing prolonged sub-MIC effects
      appeared to contribute to the outgrowth of isogenic resistant strains. The
      association between dosing and resistance emergence observed in the current
      investigation is disparate from that described for antimicrobial compounds with
      cidal killing characteristics. The inhibitory or static antimicrobial activity of
      the triazole compounds may explain these differences.

PMID- 16801416
TI  - In vivo fluconazole pharmacodynamics and resistance development in a previously
      susceptible Candida albicans population examined by microbiologic and
      transcriptional profiling.
AB  - Antimicrobial drug resistance can limit the ability to effectively treat
      patients. Numerous factors have been proposed to impact the development of
      antimicrobial resistance, including those specific to the drug and the dosing
      regimen. The field of investigation that examines the relationship between dosing
      regimen and outcome is termed antimicrobial pharmacokinetics and
      pharmacodynamics. Our prior in vivo investigations examined the relationship
      between fluconazole pharmacodynamics and the modulation of isogenic resistant and
      susceptible Candida albicans populations in a mixed-inoculum design (1). The goal
      of the current studies was to examine the impact of fluconazole pharmacodynamics
      on resistance emergence from a susceptible parent population over time using a
      murine systemic-candidiasis model. Both microbiologic and transcriptional
      endpoints were examined during the evolution of cell populations. As in our
      previous investigation, the more frequently administered dosing regimen prevented
      the emergence of a resistant cell phenotype. Conversely, dosing regimens that
      produced prolonged sub-MIC concentrations were associated with resistance
      development. The studies also demonstrated a striking relationship between
      fluconazole pharmacodynamic exposures and the mRNA abundance of drug resistance
      associated efflux pumps. Global transcriptional profiling of cell populations
      during the progressive emergence of a resistance phenotype provides insight into
      the mechanisms underlying this complex physiologic process.

PMID- 16801417
TI  - Detection of influenza viruses resistant to neuraminidase inhibitors in global
      surveillance during the first 3 years of their use.
AB  - Emergence of influenza viruses with reduced susceptibility to neuraminidase
      inhibitors (NAIs) develops at a low level following drug treatment, and person-to
      person transmission of resistant virus has not been recognized to date. The
      Neuraminidase Inhibitor Susceptibility Network (NISN) was established to follow
      susceptibility of isolates and occurrence of NAI resistance at a population level
      in various parts of the world. Isolates from the WHO influenza collaborating
      centers were screened for susceptibilities to oseltamivir and zanamivir by a
      chemiluminescent enzyme inhibition assay, and those considered potentially
      resistant were analyzed by sequence analysis of the neuraminidase genes. During
      the first 3 years of NAI use (1999 to 2002), 2,287 isolates were tested. Among
      them, eight (0.33%) viruses had a >10-fold decrease in susceptibility to
      oseltamivir, one (0.22%) in 1999 to 2000, three (0.36%) in 2000 to 2001, and four
      (0.41%) in 2001 to 2002. Six had unique changes in the neuraminidase gene
      compared to neuraminidases of the same subtype in the influenza sequence
      database. Although only one of the mutations had previously been recognized in
      persons receiving NAIs, none were from patients who were known to have received
      the drugs. During the 3 years preceding NAI use, no resistant variants were
      detected among 1,054 viruses. Drug use was relatively stable during the period,
      except for an approximate 10-fold increase in oseltamivir use in Japan during the
      third year. The frequency of variants with decreased sensitivity to the NAIs did
      not increase significantly during this period, but continued surveillance is
      required, especially in regions with higher NAI use.

PMID- 16801418
TI  - CMT-type beta-lactamase TEM-125, an emerging problem for extended-spectrum beta
      lactamase detection.
AB  - The clinical strain Escherichia coli TO799 was resistant to penicillin
      clavulanate combinations and ceftazidime and was not reproducibly detected as an
      extended-spectrum beta-lactamase (ESBL) according to the standards of the
      Clinical Laboratory Standards Institute (CLSI; formerly NCCLS) and the national
      guidelines of the French Society for Microbiology (Comite de l'Antibiogramme de
      la Societe Francaise de Microbiologie). A novel beta-lactamase, designated TEM
      125, was responsible for this phenotype. TEM-125 harbors a complex association of
      mutations previously described in the ESBL TEM-12 and in the inhibitor-resistant
      beta-lactamase TEM-39. TEM-125 is the first complex mutant TEM to present
      hydrolytic activity against ceftazidime (kcat, 3.7 s(-1)) together with a high
      level of resistance to clavulanate (50% inhibitory concentration, 13.6 microM).
      The discovery of such an ESBL, which is difficult to detect by the usual ESBL
      detection methods, confirms the emergence of a complex mutant TEM subgroup and
      highlights the need to evaluate detection methods so as to avoid possible
      therapeutic failures.

PMID- 16801419
TI  - Enteroviral meningitis: natural history and outcome of pleconaril therapy.
AB  - Enteroviral meningitis causes appreciable morbidity in adults, including
      hospitalization, decreased activity, and headache. Limited data define the
      natural history of disease. No antiviral therapeutic agent has demonstrated
      improved outcome in controlled clinical trials. Pleconaril, an inhibitor of
      enterovirus replication, was tested in two placebo-controlled clinical trials. Of
      607 randomized patients in a multicenter, double-blind placebo-controlled study
      of pleconaril (200 mg three times daily versus an identical-appearing placebo),
      240 patients were confirmed to have enterovirus infection. The time to headache
      resolution was evaluated by using Kaplan-Meier survival methodology. A Cox
      regression model evaluated multivariate factors associated with disease
      resolution. Resolution of headache in patients with concomitant moderate to
      severe nausea at baseline occurred at a median of 9.5 days in the absence of
      therapy and was reduced to 7.0 days for pleconaril recipients (P = 0.009). For a
      headache score of > 5 alone, treated patients resolved headache significantly
      more rapidly (P = 0.005). Males resolved headache 50% faster than females.
      Regardless of randomization group, patients with a baseline headache score of 5
      or greater resolved headache 50% more slowly than patients with a baseline
      headache score of 4. No differences in either clinical or laboratory adverse
      events were noted. Over 50% of untreated patients had a persistent headache that
      was greater than 1 week in duration. Pleconaril shortened the course of illness
      compared to placebo recipients, especially in the early disease course. However,
      the benefit was achieved only modestly in a subgroup analysis of patients with
      more severe disease after adjusting for confounding variables.

PMID- 16801420
TI  - Accelerated denaturation of hemoglobin and the antimalarial action of
      chloroquine.
AB  - To study the antimalarial action of chloroquine, normal mouse erythrocytes were
      used as surrogates for erythrocytoid bodies. These bodies form in the endosomes
      of intraerythrocytic malaria parasites as they feed on their host and consist of
      erythrocyte cytoplasm enclosed in a vestige of the erythrocyte membrane. In
      suspensions of normal erythrocytes or lysates (equivalent to 5 microl of
      erythrocytes per ml in each case), hemoglobin underwent denaturation when it was
      incubated at 38 degrees C in 150 mM sodium acetate (pH 5). It is reasonable to
      assume that the same phenomenon occurs in acidic endosomes. Addition of 100
      microM chloroquine to the incubation mixture caused the rate of hemoglobin
      denaturation to double to 40 nanomoles per hour per ml of packed erythrocytes.
      This effect required the presence of erythrocyte stroma and was inhibited by
      reducing the temperature to 24 degrees C or increasing the pH to 6. We propose
      that the primary antimalarial action of chloroquine is to bind to
      ferriprotoporphyrin IX (FP) and remove it from oxidized hemoglobin, thus
      producing toxic FP-chloroquine complexes and an excess of denatured globin.
      Furthermore, we suggest that these substances inhibit endosomal maturation and
      thereby cause hemoglobin accumulation in immature endosomes and masking of the
      lipids needed for FP dimerization. The term "masking" is used to signify that
      unsaturated lipids are present in parasitized erythrocytes but are specifically
      unavailable to promote FP dimerization.

PMID- 16801421
TI  - The antimalarial artemisinin synergizes with antibiotics to protect against
      lethal live Escherichia coli challenge by decreasing proinflammatory cytokine
      release.
AB  - In the present study artemisinin (ART) was found to have potent anti-inflammatory
      effects in animal models of sepsis induced by CpG-containing oligodeoxy
      nucleotides (CpG ODN), lipopolysaccharide (LPS), heat-killed Escherichia coli
      35218 or live E. coli. Furthermore, we found that ART protected mice from a
      lethal challenge by CpG ODN, LPS, or heat-killed E. coli in a dose-dependent
      manner and that the protection was related to a reduction in serum tumor necrosis
      factor alpha (TNF-alpha). More significantly, the administration of ART together
      with ampicillin or unasyn (a complex of ampicillin and sulbactam) decreased
      mortality from 100 to 66.7% or 33.3%, respectively, in mice subjected to a lethal
      live E. coli challenge. Together with the observation that ART alone does not
      inhibit bacterial growth, this result suggests that ART protection is achieved as
      a result of its anti-inflammatory activity rather than an antimicrobial effect.
      In RAW264.7 cells, pretreatment with ART potently inhibited TNF-alpha and
      interleukin-6 release induced by CpG ODN, LPS, or heat-killed E. coli in a dose-
      and time-dependent manner. Experiments utilizing affinity sensor technology
      revealed no direct binding of ART with CpG ODN or LPS. Flow cytometry further
      showed that ART did not alter binding of CpG ODN to cell surfaces or the
      internalization of CpG ODN. In addition, upregulated levels of TLR9 and TLR4 mRNA
      were not attenuated by ART treatment. ART treatment did, however, block the NF
      kappaB activation induced by CpG ODN, LPS, or heat-killed E. coli. These findings
      provide compelling evidence that ART may be an important potential drug for
      sepsis treatment.

PMID- 16801422
TI  - Mechanism of drug resistance in clonally related clinical isolates of Vibrio
      fluvialis isolated in Kolkata, India.
AB  - The molecular mechanisms of drug resistance in 19 strains of Vibrio fluvialis
      isolated from 1998 to 2002 in Kolkata, India, were investigated. Class 1
      integrons were detected in eight strains, and four strains were found to carry
      SXT integrases. In the presence of carbonyl cyanide m-chlorophenylhydrazone or
      reserpine, all nalidixic acid- and ciprofloxacin-resistant strains became
      sensitive, suggesting that drug efflux plays a major role in quinolone resistance
      in V. fluvialis. It was further seen that strains which had MICs of > 25
      microg/ml for nalidixic acid had a sense mutation (Ser to Ile) at position 83 of
      the quinolone resistance-determining region of gyrA. All except one of the
      integron- and SXT integrase-bearing strains belonged to the same ribotype.

PMID- 16801423
TI  - Clonal dissemination of a CTX-M-15 beta-lactamase-producing Escherichia coli
      strain in the Paris area, Tunis, and Bangui.
AB  - One hundred twenty CTX-M-15-producing Escherichia coli strains isolated in 10
      different hospitals from Paris (France), in the Hospital Charles Nicolle in Tunis
      (Tunisia), and in the Pasteur Institute in Bangui, Central African Republic
      (CAR), between 2000 and 2004 were studied. Eighty isolates, recovered from the
      three countries, were clonally related by repetitive extragenic palindromic PCR
      and pulsed-field gel electrophoresis. Various resistance profiles were identified
      among these clonal strains. After conjugation or electroporation of plasmids from
      E. coli strains representative of each profile and each geographic region, we
      observed seven resistance profiles in the recipient strains. Incompatibility
      typing showed that all the plasmids transferred from the clonal strains studied,
      except one, belonged to the incompatibility group FII. They all shared a
      multidrug resistance region (MDR) resembling the MDR region located in pC15-1a, a
      plasmid associated with an outbreak of a CTX-M-15-producing E. coli strain in
      Canada. They also shared the common backbone of an apparent mosaic plasmid,
      including several features present in pC15-1a and in pRSB107, a plasmid isolated
      from a sewage treatment plant. This study suggests that although the plasmid
      borne blaCTX-M-15 gene could be transferred horizontally, its dissemination
      between France, Tunisia, and CAR was due primarily to its residence in an E. coli
      clone with a strong propensity for dissemination.

PMID- 16801424
TI  - Aziridine-2,3-dicarboxylates, peptidomimetic cysteine protease inhibitors with
      antileishmanial activity.
AB  - Chemotherapy of leishmaniasis is mainly based on antimonials. However, they are
      extremely toxic and cause serious side effects, and there is a worldwide
      increasing frequency of chemoresistance to antimonials. These issues emphasize
      the urgent need for affordable alternative drugs against leishmaniasis.
      Leishmania cysteine proteases are essential for parasite growth, differentiation,
      pathogenicity, and virulence and are thus attractive targets for combating
      leishmaniasis. Herein we demonstrate that the cysteine protease inhibitors
      aziridine-2,3-dicarboxylates 13b and 13e impaired promastigote growth at mid
      micromolar concentrations and decreased the infection rate of peritoneal
      macrophages at concentrations 8- to 13-fold lower than those needed to inhibit
      parasite replication. Simultaneous treatment of infected cells with compound 13b
      and gamma interferon resulted in an even further reduction of the concentration
      needed for a significant decrease in macrophage infection rate. Notably,
      treatment with the compounds alone modulated the cytokine secretion of infected
      macrophages, with increased levels of interleukin-12 and tumor necrosis factor
      alpha. Furthermore, the decreased infection rate in the presence of compound 13b
      correlated with increased nitric oxide production by macrophages. Importantly, at
      the concentrations used herein, compounds 13b and 13e were not toxic against
      fibroblasts, macrophages, or dendritic cells. Together, these results suggest
      that the aziridine-2,3-dicarboxylates 13b and 13e are potential antileishmanial
      lead compounds with low toxicity against host cells and selective antiparasitic
      effects.

PMID- 16801425
TI  - Low-level resistance of Staphylococcus aureus to thrombin-induced platelet
      microbicidal protein 1 in vitro associated with qacA gene carriage is independent
      of multidrug efflux pump activity.
AB  - Thrombin-induced platelet microbial protein 1 (tPMP-1), a cationic antimicrobial
      polypeptide released from thrombin-stimulated rabbit platelets, targets the
      Staphylococcus aureus cytoplasmic membrane to initiate its microbicidal effects.
      In vitro resistance to tPMP-1 correlates with survival advantages in vivo. In S.
      aureus, the plasmid-carried qacA gene encodes a multidrug transporter, conferring
      resistance to organic cations (e.g., ethidium [Et]) via proton motive force (PMF)
      energized export. We previously showed that qacA also confers a tPMP-1-resistant
      (tPMP-1r) phenotype in vitro. The current study evaluated whether (i)
      transporters encoded by the qacB and qacC multidrug resistance genes also confer
      tPMP-1r and (ii) tPMP-1r mediated by qacA is dependent on efflux pump activity.
      In contrast to tPMP-1r qacA-bearing strains, the parental strain and its isogenic
      qacB- and qacC-containing strains were tPMP-1 susceptible (tPMP-1s). Efflux pump
      inhibition by cyanide m-chlorophenylhydrazone abrogated Etr, but not tPMP-1r, in
      the qacA-bearing strain. In synergy assays, exposure of the qacA-bearing strain
      to tPMP-1 did not affect the susceptibility of Et (ruling out Et-tPMP-1
      cotransport). The following cytoplasmic membrane parameters did not differ
      significantly between the qacA-bearing and parental strains: contents of the
      major phospholipids; asymmetric distributions of the positively charged species,
      lysyl-phosphotidylglycerol; fatty acid composition; and relative surface charge.
      Of note, the qacA-bearing strain exhibited greater membrane fluidity than that of
      the parental, qacB-, or qacC-bearing strain. In conclusion, among these families
      of efflux pumps, only the multidrug transporter encoded by qacA conferred a tPMP
      1r phenotype. These data suggest that qacA-encoded tPMP-1r results from the
      impact of a specific transporter upon membrane structure or function unrelated to
      PMF-dependent peptide efflux.

PMID- 16801426
TI  - Pharmacokinetics of unbound linezolid in plasma and tissue interstitium of
      critically ill patients after multiple dosing using microdialysis.
AB  - The antimicrobial agent linezolid is approved for the treatment of severe
      infections caused by, e.g., methicillin-resistant Staphylococcus strains. In
      order to evaluate the penetration of linezolid into the interstitial space fluid
      (ISF) of subcutaneous adipose tissue and skeletal muscle of the target
      population, a microdialysis study was performed with 12 patients with sepsis or
      septic shock after multiple intravenous infusions. Unbound linezolid
      concentrations were determined for plasma and microdialysates by use of a
      validated high-performance liquid chromatography method. Individual compartmental
      pharmacokinetic (PK) analysis was performed using WinNonlin. In vivo
      microdialysis was found to be feasible for the determination of unbound linezolid
      concentrations at steady state in the ISF of critically ill patients. On average,
      linezolid showed good distribution into ISF but with high interindividual
      variability. A two-compartment model was fitted to unbound concentrations in
      plasma with a geometric mean distribution volume of 62.9 liters and a mean
      clearance of 9.18 liters/h at steady state. However, disposition characteristics
      changed intraindividually within the time course. In addition, an integrated
      model for simultaneous prediction of concentrations in all matrices was developed
      and revealed similar results. Based on the model-predicted unbound concentrations
      in ISF, a scheme of more-frequent daily dosing of linezolid for some critically
      ill patients might be taken into consideration to avoid subinhibitory unbound
      concentrations in the infected tissue. The developed integrated model will be a
      valuable basis for further PK data analysis to explore refined dosing guidelines
      that achieve effective antimicrobial therapy in all patients by use of the
      population PK approach.

PMID- 16801427
TI  - Results obtained with various antifungal susceptibility testing methods do not
      predict early clinical outcome in patients with cryptococcosis.
AB  - The in vitro susceptibilities of Cryptococcus neoformans isolates from
      consecutive human immunodeficiency virus-positive and -negative patients to the
      antifungal agents fluconazole, amphotericin B, and flucytosine were determined by
      different techniques, including the CLSI method, Etest, and broth microdilution
      in yeast nitrogen base (YNB) medium, during a multicenter prospective study in
      France. The relationship between the in vitro data and the clinical outcome 2
      weeks after the initiation of antifungal therapy was assessed. In addition, the
      correlation between the strain serotype and the in vitro activities of the
      antifungals was determined, and the susceptibility results obtained with the
      different techniques were also compared. Thirty-seven patients received a
      combination of amphotericin B with flucytosine as first-line therapy, 22 were
      treated with amphotericin B alone, and 15 received fluconazole alone. Whatever
      the antifungal tested, there was no trend toward higher MICs for strains isolated
      from patients who failed to respond to a given therapy compared to those from
      patients who did not with either the CLSI method, Etest, or broth microdilution
      in YNB medium. The MICs obtained by the CLSI or Etest method were significantly
      lower for serotype D strains than for serotype A strains for both fluconazole and
      amphotericin B, while flucytosine MICs were not different according to serotype.
      These findings suggest that the in vitro antifungal susceptibility of C.
      neoformans, as determined with the techniques used, is not able to predict the
      early clinical outcome in patients with cryptococcosis.

PMID- 16801428
TI  - Intracellular metabolism and in vitro activity of tenofovir against hepatitis B
      virus.
AB  - Tenofovir is an acyclic nucleotide analog with activity against human
      immunodeficiency virus (HIV) and hepatitis B virus (HBV). Tenofovir disoproxil
      fumarate (tenofovir DF), a bis-alkoxyester prodrug of tenofovir, is approved for
      the treatment of HIV and is currently being developed to treat chronic hepatitis
      B. In this report, we further characterize the in vitro activity of tenofovir
      against HBV as well as its metabolism in hepatic cells. We show that tenofovir is
      efficiently phosphorylated to tenofovir diphosphate (TFV-DP) in both HepG2 cells
      and primary human hepatocytes. TFV-DP has a long intracellular half-life (95 h)
      and is a potent and competitive inhibitor of HBV polymerase (Ki = 0.18 microM).
      Tenofovir has a 50% effective concentration of 1.1 microM against HBV in cell
      based assays, and potency is improved > 50-fold by the addition of bis-isoproxil
      progroups. Tenofovir has previously demonstrated full activity against lamivudine
      resistant HBV in vitro and clinically. Here we show that the major adefovir
      resistance mutation, rtN236T, confers three- to fourfold-reduced susceptibility
      to tenofovir in cell culture; the clinical significance of this susceptibility
      shift has not yet been determined. The rtA194T HBV polymerase mutation recently
      identified in tenofovir DF-treated HIV/HBV-coinfected patients did not confer in
      vitro resistance to tenofovir as a single mutation or in a lamivudine-resistant
      viral background. Overall, the antiviral and metabolic profile of tenofovir
      supports its development for the treatment of chronic hepatitis B.

PMID- 16801430
TI  - Molecular evolution of beta-lactam-resistant Haemophilus influenzae: 9-year
      surveillance of penicillin-binding protein 3 mutations in isolates from Japan.
AB  - A total of 621 clinical isolates of Haemophilus influenzae collected in Japan
      between 1995 and 2003 were studied for their susceptibilities to several
      antimicrobial agents, beta-lactamase production, and amino acid substitutions in
      penicillin-binding protein 3 (PBP 3). Over the four study periods (first period,
      1995 to 1996; second period, 1997 to 1998; third period, 2000 to 2001; fourth
      period, 2002 to 2003), the susceptibilities to beta-lactam agents decreased and
      the incidence of isolates with substitutions at positions 377, 385, 389, 517,
      and/or 526 in PBP 3 increased from 28.8% to 52.0%. Five hundred seventy-one beta
      lactamase-nonproducing isolates were grouped into 18 classes, based on the
      pattern of the five mutations in PBP 3. The Asp526Lys substitution led to 6.0-,
      4.3-, 2.4-, and 5.4-fold increases in amoxicillin-clavulanic acid, cefdinir,
      cefditoren, and faropenem resistance, respectively. PBP 3 with multiple
      substitutions (Met377Ile, Ser385Thr, and/or Leu389Phe) together with Asp526Lys
      resulted in increased resistance compared to that for PBP 3 with the Asp526Lys
      substitution alone. These results indicate that mutations at these five positions
      increased resistance to most beta-lactams. Although a significant change in the
      prevalence of beta-lactamase-producing strains was not observed, the proportions
      of those possessing both PBP 3 alterations and beta-lactamase production have
      slightly increased (from 1.4% to 5.0%). The ROB-1 beta-lactamase was rare, but
      this is the first report of this beta-lactamase in Japan.

PMID- 16801429
TI  - Interaction of antimicrobial peptide temporin L with lipopolysaccharide in vitro
      and in experimental rat models of septic shock caused by gram-negative bacteria.
AB  - Sepsis remains a major cause of morbidity and mortality in hospitalized patients,
      despite intense efforts to improve survival. The primary lead for septic shock
      results from activation of host effector cells by endotoxin, the
      lipopolysaccharide (LPS) associated with cell membranes of gram-negative
      bacteria. For these reasons, the quest for compounds with antiendotoxin
      properties is actively pursued. We investigated the efficacy of the amphibian
      skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro
      and counteracting its effects in vivo. Temporin L strongly bound to purified E.
      coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and
      readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity
      of temporin L against E. coli was progressively inhibited by increasing
      concentrations of LPS added to the medium, further confirming the peptide's
      affinity for endotoxin. Antimicrobial assays showed that temporin L interacted
      synergistically with the clinically used beta-lactam antibiotics piperacillin and
      imipenem. Therefore, we characterized the activity of temporin L when combined
      with imipenem and piperacillin in the prevention of lethality in two rat models
      of septic shock, measuring bacterial growth in blood and intra-abdominal fluid,
      endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma,
      and lethality. With respect to controls and single-drug treatments, the
      simultaneous administration of temporin L and beta-lactams produced the highest
      antimicrobial activities and the strongest reduction in plasma endotoxin and TNF
      alpha levels, resulting in the highest survival rates.

PMID- 16801431
TI  - New cluster of plasmid-located class 1 integrons in Vibrio cholerae O1 and a
      dfrA15 cassette-containing integron in Vibrio parahaemolyticus isolated in
      Angola.
AB  - The resistance profile and its correlation with mobile genetic elements were
      investigated in 11 Vibrio cholerae O1 and 2 Vibrio parahaemolyticus clinical
      isolates, as well as in 1 V. cholerae O1 and 1 V. cholerae non-O1 environmental
      isolate, isolated between 1991 and 1996 in different provinces of Angola. All
      clinical isolates of V. cholerae O1 were resistant to ampicillin,
      chloramphenicol, trimethoprim, sulfamethoxazole, and tetracycline. They also
      contained a large conjugative plasmid (p3iANG) with a set of three class 1
      integrons harboring dfrA15, blaP1, and qacH-aadA8 cassettes, which code for
      resistance to trimethoprim, beta-lactams, quaternary ammonium compounds, and
      aminoglycosides, clustered in a 19-kb region. Chloramphenicol (cat1), kanamycin
      (aph), sulfonamide (sul2), and tetracycline (tetG) resistance genes were also
      carried on the plasmid within the same 19-kb region. A chromosomal integron
      containing the dfrA15 cassette was also revealed in V. parahaemolyticus strains.
      SXT integrase genes were present in six V. cholerae isolates but apparently were
      not associated with known SXT-associated resistance genes. This study indicates
      that plasmids and integrons contributed mainly to the circulation of multiple
      drug resistance determinants in Vibrio strains from Angola.

PMID- 16801432
TI  - The Cfr rRNA methyltransferase confers resistance to Phenicols, Lincosamides,
      Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics.
AB  - A novel multidrug resistance phenotype mediated by the Cfr rRNA methyltransferase
      is observed in Staphylococcus aureus and Escherichia coli. The cfr gene has
      previously been identified as a phenicol and lincosamide resistance gene on
      plasmids isolated from Staphylococcus spp. of animal origin and recently shown to
      encode a methyltransferase that modifies 23S rRNA at A2503. Antimicrobial
      susceptibility testing shows that S. aureus and E. coli strains expressing the
      cfr gene exhibit elevated MICs to a number of chemically unrelated drugs. The
      phenotype is named PhLOPSA for resistance to the following drug classes:
      Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A
      antibiotics. Each of these five drug classes contains important antimicrobial
      agents that are currently used in human and/or veterinary medicine. We find that
      binding of the PhLOPSA drugs, which bind to overlapping sites at the peptidyl
      transferase center that abut nucleotide A2503, is perturbed upon Cfr-mediated
      methylation. Decreased drug binding to Cfr-methylated ribosomes has been
      confirmed by footprinting analysis. No other rRNA methyltransferase is known to
      confer resistance to five chemically distinct classes of antimicrobials. In
      addition, the findings described in this study represent the first report of a
      gene conferring transferable resistance to pleuromutilins and oxazolidinones.

PMID- 16801433
TI  - Reverse engineering antibiotic sensitivity in a multidrug-resistant Pseudomonas
      aeruginosa isolate.
AB  - Antibiotic resistance is a pervasive and growing clinical problem. We describe an
      evaluation of a reverse engineering approach for identifying cellular mechanisms
      and genes that could be manipulated to increase antibiotic sensitivity in a
      resistant Pseudomonas aeruginosa isolate. We began by chemically mutating a
      broadly resistant isolate of P. aeruginosa and screening for mutants with
      increased sensitivity to the aminoglycoside amikacin, followed by performing
      whole-genome transcriptional profiling of the mutant and wild-type strains to
      characterize the global changes occurring as a result of the mutations. We then
      performed a series of assays to characterize the mechanisms involved in the
      increased sensitivity of the mutant strains. We report four primary results: (i)
      mutations that increase sensitivity occur at a high frequency (10(-2)) relative
      to the frequency of those that increase resistance (10(-5) to 10(-10)) and occur
      at a frequency 10(4) higher than the frequency of a single point mutation; (ii)
      transcriptional profiles were altered in sensitive mutants, resulting in overall
      expression patterns more similar to those of the sensitive laboratory strain PAO1
      than those of the parental resistant strain; (iii) genes found from
      transcriptional profiling had the more dramatic changes in expression-encoded
      functions related to cellular membrane permeability and aminoglycoside
      modification, both of which are known aminoglycoside resistance mechanisms; and
      finally, (iv) even though we did not identify the specific sites of mutation,
      several different follow-up MIC assays suggested that the mutations responsible
      for increased sensitivity differed between sensitive mutants.

PMID- 16801434
TI  - Crystal structure of the Mycobacterium fortuitum class A beta-lactamase:
      structural basis for broad substrate specificity.
AB  - beta-Lactamases are the main cause of bacterial resistance to penicillins and
      cephalosporins. Class A beta-lactamases, the largest group of beta-lactamases,
      have been found in many bacterial strains, including mycobacteria, for which no
      beta-lactamase structure has been previously reported. The crystal structure of
      the class A beta-lactamase from Mycobacterium fortuitum (MFO) has been solved at
      2.13-A resolution. The enzyme is a chromosomally encoded broad-spectrum beta
      lactamase with low specific activity on cefotaxime. Specific features of the
      active site of the class A beta-lactamase from M. fortuitum are consistent with
      its specificity profile. Arg278 and Ser237 favor cephalosporinase activity and
      could explain its broad substrate activity. The MFO active site presents
      similarities with the CTX-M type extended-spectrum beta-lactamases but lacks a
      specific feature of these enzymes, the VNYN motif (residues 103 to 106), which
      confers on CTX-M-type extended-spectrum beta-lactamases a more efficient
      cefotaximase activity.

PMID- 16801435
TI  - Emergence of a Candida krusei isolate with reduced susceptibility to caspofungin
      during therapy.
AB  - Clinical failure associated with reduced susceptibility to caspofungin has been
      described in Candida albicans and C. parapsilosis. We report a case of Candida
      krusei infection that progressed despite caspofungin therapy. Reduced microbial
      susceptibility to all three echinocandins (caspofungin, anidulafungin, and
      micafungin) was noted but was not associated with mutations in FKS1.

PMID- 16801436
TI  - Activities of alkoxyalkyl esters of cidofovir (CDV), cyclic CDV, and (S)-9-(3
      hydroxy-2-phosphonylmethoxypropyl)adenine against orthopoxviruses in cell
      monolayers and in organotypic cultures.
AB  - The potencies of several alkoxyalkyl esters of acyclic nucleoside phosphonates
      against vaccinia virus and cowpox virus were evaluated in cell monolayers and
      three-dimensional epithelial raft cultures. Prodrugs were at least 20-fold more
      active than their parent compounds. Octadecycloxyethyl-(S)-9-(3-hydroxy-2
      phosphonylmethoxypropyl)adenine emerged as the most potent derivative.

PMID- 16801437
TI  - Activities of ceftobiprole and other beta-lactams against Streptococcus
      pneumoniae clinical isolates from the United States with defined substitutions in
      penicillin-binding proteins PBP 1a, PBP 2b, and PBP 2x.
AB  - The activities of ceftobiprole and other beta-lactams were examined with 30
      Streptococcus pneumoniae isolates containing multiple pbp1a, pbp2b, and pbp2x
      mutations. The highest ceftobiprole MIC was 1 microg/ml, while the comparator
      MICs were 16 to 64 microg/ml. Fifty percent inhibitory concentrations for
      penicillin-binding protein 2x were 0.5 microg/ml (ceftobiprole) and 4 microg/ml
      (ceftriaxone) in a penicillin- and ceftriaxone-resistant isolate.

PMID- 16801438
TI  - A Phe389Leu substitution in ergA confers terbinafine resistance in Aspergillus
      fumigatus.
AB  - Replacement of phenylalanine with leucine at position 391 in squalene epoxidase
      was identified as being responsible for terbinafine resistance in mutants of
      Aspergillus nidulans. The equivalent mutation was engineered into the ergA gene
      of Aspergillus fumigatus, resulting in an F389L substitution that also conferred
      resistance to this pathogenic mold.

PMID- 16801439
TI  - Effect of a selective decontamination of the digestive tract regimen including
      parenteral cefepime on establishment of intestinal colonization with vancomycin
      resistant Enterococcus spp. and Klebsiella pneumoniae in mice.
AB  - In mice, a selective decontamination of the digestive tract regimen consisting of
      orogastric tobramycin, polymyxin E, and amphotericin B in combination with
      subcutaneous cefepime inhibited gram-negative bacilli, including Klebsiella
      pneumoniae, and did not promote vancomycin-resistant Enterococcus spp. (VRE)
      colonization. However, concurrent administration of subcutaneous ampicillin
      sulbactam resulted in promotion of VRE.

PMID- 16801440
TI  - Risk factors for isolation of strains susceptible only to polymyxin among
      patients with Pseudomonas aeruginosa bacteremia.
AB  - We conducted a case-control study to identify risk factors associated with the
      isolation of Pseudomonas aeruginosa strains susceptible only to polymyxin from
      blood by comparing data between 16 patients with blood isolates that were
      susceptible only to polymyxins and 40 patients with blood isolates that were
      susceptible to carbapenems. The multivariable analysis showed that exposure to
      carbapenems was associated with the development of P. aeruginosa bacteremia
      susceptible only to polymyxin (odds ratio, 9.0; 95% confidence interval, 2.4 to
      34.3; P = 0.001).

PMID- 16801441
TI  - Common region CR1 for expression of antibiotic resistance genes.
AB  - The CR1 element defined by an orf513 gene encoding a putative recombinase and a
      recombination crossover site has been identified upstream of several antibiotic
      resistance genes in Enterobacteriaceae. This CR1 element was shown to bring
      promoter sequences that play a role in the expression of unrelated antibiotic
      resistance genes.

PMID- 16801442
TI  - In vitro and in vivo assessment of linezolid combined with ertapenem: a highly
      synergistic combination against methicillin-resistant Staphylococcus aureus.
AB  - Linezolid in combination with ertapenem showed in vitro synergy against
      methicillin-resistant Staphylococcus aureus strains. We confirmed this
      interaction in vivo by using a rabbit endocarditis experimental model and
      simulation of the human pharmacokinetics in animals for both antibiotics.
      Linezolid plus ertapenem exhibited highly synergistic activity in vivo after 4
      days of treatment.

PMID- 16801443
TI  - Polyphenols reduce gastritis induced by Helicobacter pylori infection or VacA
      toxin administration in mice.
AB  - Helicobacter pylori colonizes the human gastric mucosa, causing inflammation that
      leads to atrophic gastritis, and it can cause peptic ulcer and gastric cancer. We
      show that polyphenol administration to mice experimentally infected by H. pylori
      or treated with VacA toxin can limit gastric epithelium damage, an effect that
      may be linked to VacA inhibition.

PMID- 16801444
TI  - Risk factors for selection of the L74I reverse transcriptase mutation in human
      immunodeficiency virus type 1-infected patients.
AB  - We analyzed 3,475 human immunodeficiency virus sequences and 241 therapeutic
      histories. The L74I mutation was carried by 7% of viruses. L74I was strongly
      associated with T215F, K70R, and V75M/S/T/A mutations and increased with the
      number of thymidine analog mutations. It seemed to be linked to the use of
      abacavir or efavirenz.

PMID- 16801445
TI  - Effect of cell culture conditions on the anticytomegalovirus activity of
      maribavir.
AB  - The cytomegalovirus UL97 kinase inhibitor maribavir suppressed viral growth more
      effectively in lung fibroblasts than in skin fibroblasts, and some cellular
      kinase inhibitors enhanced its antiviral activity. These effects influence the
      phenotypic assay of drug susceptibility and suggest the possibility of
      therapeutically useful combinations of maribavir and cellular kinase inhibitors.

PMID- 16801446
TI  - Intrinsic macrolide resistance of the Mycobacterium tuberculosis complex is
      inducible.
AB  - Mycobacterium tuberculosis is intrinsically resistant to macrolides, a
      characteristic associated with expression of the erm(37) gene. This intrinsic
      resistance was found to be inducible with clarithromycin and the ketolide
      HMR3004. Furthermore, underlying the phenotypic induction was an increase in
      erm(37) mRNA levels.

PMID- 16801447
TI  - Prospective determination of plasma imipenem concentrations in critically ill
      children.
AB  - Plasma imipenem concentrations were measured in 19 critically ill children
      (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual
      variations (2 to 4x at peak and >10x at trough concentrations) resulted in
      unpredictable plasma levels in several children. To avoid subtherapeutic drug
      levels, we recommend treatment with at least 100 mg/kg of body weight/day of
      imipenem-cilastatin for critically ill children requiring such therapy.

PMID- 16801448
TI  - Characterizing the effects of caspofungin on Candida albicans, Candida
      parapsilosis, and Candida glabrata isolates by simultaneous time-kill and
      postantifungal-effect experiments.
AB  - We measured time-kills and postantifungal effects (PAFEs) of caspofungin against
      Candida albicans, C. parapsilosis, and C. glabrata isolates. One-hour exposure to
      caspofungin during PAFE experiments accounted for the majority of killing during
      time-kill experiments. Regrowth of all isolates was inhibited for at least 24 h
      following drug washout.

PMID- 16801449
TI  - Naturally occurring extended-spectrum cephalosporinases in Escherichia coli.
AB  - Genetic and functional characterization of the cephalosporinases produced by 65
      clonally unrelated clinical Escherichia coli isolates revealed genetic diversity
      of the ampC genes and showed that Gln287, Cys287, Pro296, Leu298, and Phe350
      substitutions were involved in extension of the hydrolysis spectrum to include
      ceftazidime and cefepime.

PMID- 16801450
TI  - Interactions between glycopeptides and beta-lactams against isogenic pairs of
      teicoplanin-susceptible and -resistant strains of Staphylococcus haemolyticus.
AB  - Four isogenic derivatives with stably increased glycopeptide MICs (all become
      resistant to teicoplanin) were obtained from four glycopeptide-susceptible
      clinical isolates of Staphylococcus haemolyticus. All strains were extensively
      analyzed and compared for a number of distinctive features. In particular, the
      results provided insights into the puzzling issue of antistaphylococcal
      interactions between glycopeptides and beta-lactams, especially the paradox of
      double zones around beta-lactam disks and the relationships between autolysis
      rate and type of interaction.

PMID- 16801451
TI  - Activity of retapamulin (SB-275833), a novel pleuromutilin, against selected
      resistant gram-positive cocci.
AB  - Retapamulin (SB-275833), the first pleuromutilin to be developed for human
      topical use, was tested against a selected population of staphylococci and beta
      hemolytic streptococci. The MIC90 results for retapamulin were 0.12 microg/ml for
      Staphylococcus aureus and < or = 0.03 microg/ml for Streptococcus pyogenes; no
      cross-resistance was observed for organism subsets resistant to oxacillin,
      erythromycin, or mupirocin.

PMID- 16801452
TI  - Interaction between posaconazole and caspofungin in concomitant treatment of mice
      with systemic Aspergillus infection.
AB  - The interaction of posaconazole and caspofungin was evaluated in concomitant
      treatment of Aspergillus fumigatus (two strains) or A. flavus (one strain)
      systemic infections in immunocompetent mice. Survival curves for mice treated
      with the combinations were compared statistically with those for mice treated
      with the component monotherapies. No antagonism was observed.

PMID- 16801453
TI  - A death-promoting role for extracellular signal-regulated kinase.
AB  - Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), which are
      members of the mitogen-activated protein kinase superfamily, have been well
      characterized and are known to be involved in cell survival; however, recent
      evidence suggests that the activation of ERK1/2 also contributes to cell death in
      some cell types and organs under certain conditions. For example, ERK1/2 is
      activated in neuronal and renal epithelial cells upon exposure to oxidative
      stress and toxicants and deprivation of growth factors, and inhibition of the ERK
      pathway blocks apoptosis. ERK activation also occurs in animal models of ischemia
      and trauma-induced brain injury and cisplatin-induced renal injury, and
      inactivation of ERK reduces the extent of tissue damage. In some studies, ERK has
      been implicated in apoptotic events upstream of mitochondrial cytochrome c
      release, whereas other studies have suggested the converse that ERK acts
      downstream of mitochondrial events and upstream of caspase-3 activation. ERK also
      can contribute to cell death through the suppression of the antiapoptotic
      signaling molecule Akt. Here we summarize the evidence and mechanism of ERK
      induced apoptosis in both cell culture and in animal models.

PMID- 16801454
TI  - Separation of binding affinity and intrinsic activity of the potent mu-opioid 14
      methoxymetopon.
AB  - Receptor binding studies of 5,14-O-dimethyloxymorphone (14-methoxymetopon) in
      brain membranes have established its high affinity for mu-binding sites, but its
      analgesic potency far exceeds the modest increase in binding affinity relative to
      other opioids. The current study has established the selectivity of [(3)H]14
      methoxymetopon for mu sites in calf striatal membranes and for a number of full
      length splice variants of the cloned murine mu-opioid receptor 1 (mMOR-1) in
      transfected cell lines. The binding affinity of [(3)H]14-methoxymetopon for the
      variants expressed in Chinese hamster ovary cells was quite high, with K(D)
      values around 0.2 nM for all of the variants with the exception of mMOR-1F (K(D)
      of 1.2 nM). The affinity for most of the expressed variants was greater than that
      seen in the brain membranes (K(D) of 0.99 nM). Functionally, in guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding assays with the MOR-1
      variants, 14-methoxymetopon and the mu-opioid peptide [d-Ala(2),N-Me
      Phe(4),Gly(5)-ol]-enkephalin (DAMGO) showed similar efficacies, as determined by
      maximal stimulation, but 14-methoxymetopon was up to 65-fold more potent than
      DAMGO. The greatest difference was seen with mMOR-1E and the least with mMOR-1C,
      which displayed only a 10-fold difference. These potency differences in the
      stimulation of [(35)S]GTPgammaS binding far exceeded the differences in binding
      affinity. The differences between 14-methoxymetopon and DAMGO remained after
      normalizing the potency shifts based upon receptor binding affinities and varied
      from 1.2-fold with mMOR-1C to 21-fold for mMOR-1 and 42-fold with mMOR-1F. Thus,
      14-methoxymetopon is a potent agonist against all of the mMOR-1 splice variants,
      but its potency ranged widely despite similar binding affinities for most of the
      variants and may give insight into its unusual pharmacological profile.

PMID- 16801455
TI  - Mitochondrial arginase II modulates nitric-oxide synthesis through nonfreely
      exchangeable L-arginine pools in human endothelial cells.
AB  - Reduced synthesis of nitric oxide (NO) contributes to the endothelial dysfunction
      and may be related to limited availability of L-arginine, the common substrate of
      constitutive nitric-oxide synthase (NOS) and cytosolic arginase I and
      mitochondrial arginase II. To determine whether arginases modulate the
      endothelial NO synthesis, we investigated the effects of the competitive arginase
      inhibitor N(omega)-hydroxy-nor-L-arginine (Nor-NOHA) on the activity of NOS,
      arginases, and L-arginine transporter and on NO release at surface of human
      umbilical vein endothelial cells (HUVECs). In unstimulated cells, Nor-NOHA dose
      dependently reduced the arginase activity with maximal inhibition at 20 microM.
      When HUVECs were stimulated by thrombin without extracellular L-arginine, Nor
      NOHA dose-dependently increased the NOS activity and the NO release with maximal
      effects at 20 microM. Extracellular L-arginine also dose-dependently increased NO
      release and arginase activity. When HUVECs were stimulated by thrombin in the
      presence of 100 microM L-arginine, NOS activity and NO release were similar in
      untreated and Nor-NOHA-treated cells. However, despite activation of L-arginine
      uptake, the inhibition of arginase activity by Nor-NOHA was still significant.
      The depletion of freely exchangeable L-arginine pools with extracellular L-lysine
      did not prevent Nor-NOHA from increasing the NO release. This indicates the
      presence of pools, which are accessible to NOS and arginase, but not
      exchangeable. Interestingly, the mitochondrial arginase II was constitutively
      expressed, whereas the cytosolic arginase I was barely detectable in HUVECs.
      These data suggest that endothelial NO synthesis depends on the activity of
      arginase II in mitochondria and l-arginine carriers in cell membrane.

PMID- 16801456
TI  - Greater susceptibility of the sarcoplasmic reticulum to H2O2 injuries in
      diaphragm muscle from mdx mice.
AB  - The aim of the present study was to investigate the direct effects of a reactive
      oxygen species, H(2)O(2), on the contractile function and sarcoplasmic reticulum
      properties of dystrophin-deficient diaphragm using chemically skinned fibers and
      sarcoplasmic reticulum vesicle preparations. The results obtained using Triton X
      100-skinned fibers demonstrate that exposure to 1 mM H(2)O(2) had similar effects
      on the maximal Ca(2+)-activated tension and on the Ca(2+) sensitivity of the
      contractile apparatus of diaphragm fibers in Bl10 and mdx mice. The effects of
      H(2)O(2) were also assessed on sarcoplasmic reticulum function using saponin
      skinned fibers and sarcoplasmic reticulum vesicle preparations. We found that
      H(2)O(2) induced changes in sarcoplasmic reticulum properties, particularly in
      the Ca(2+) pump function. The most important finding was that diaphragm muscle
      from mdx mice displayed increased sensitivity to the oxidant. Furthermore, in
      isolated superfused diaphragm muscle from mdx mice, the data demonstrate that the
      amount of superoxide anion produced under fatiguing conditions was increased. Our
      study shows that the sarcoplasmic reticulum, and the Ca(2+) pump in particular,
      in dystrophin-deficient muscles display increased susceptibility to H(2)O(2)
      injuries. This suggests that free radicals might, therefore, be involved in the
      pathophysiological pathway and dysregulation of Ca(2+) homeostasis of muscular
      dystrophy.

PMID- 16801457
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 16801458
TI  - Reducing delay in seeking treatment by patients with acute coronary syndrome and
      stroke: a scientific statement from the American Heart Association Council on
      cardiovascular nursing and stroke council.
AB  - Patient delay in seeking treatment for acute coronary syndrome and stroke
      symptoms is the major factor limiting delivery of definitive treatment in these
      conditions. Despite decades of research and public education campaigns aimed at
      decreasing patient delay times, most patients still do not seek treatment in a
      timely manner. In this scientific statement, we summarize the evidence that (1)
      demonstrates the benefits of early treatment, (2) describes the extent of the
      problem of patient delay, (3) identifies the factors related to patient delay in
      seeking timely treatment, and (4) reveals the inadequacies of our current
      approaches to decreasing patient delay. Finally, we offer suggestions for
      clinical practice and future research.

PMID- 16801459
TI  - Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double
      blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Eisenmenger syndrome is characterized by the development of pulmonary
      arterial hypertension with consequent intracardiac right-to-left shunt and
      hypoxemia in patients with preexisting congenital heart disease. Because
      Eisenmenger syndrome is associated with increased endothelin expression, patients
      may benefit from endothelin receptor antagonism. Theoretically, interventions
      that have some effect on the systemic vascular bed could worsen the shunt and
      increase hypoxemia. METHODS AND RESULTS: The Bosentan Randomized Trial of
      Endothelin Antagonist Therapy-5 (BREATHE-5) was a 16-week, multicenter,
      randomized, double-blind, placebo-controlled study evaluating the effect of
      bosentan, a dual endothelin receptor antagonist, on systemic pulse oximetry
      (primary safety end point) and pulmonary vascular resistance (primary efficacy
      end point) in patients with World Health Organization functional class III
      Eisenmenger syndrome. Hemodynamics were assessed by right- and left-heart
      catheterization. Secondary end points included exercise capacity assessed by 6
      minute walk distance, additional hemodynamic parameters, functional capacity, and
      safety. Fifty-four patients were randomized 2:1 to bosentan (n=37) or placebo
      (n=17) for 16 weeks. The placebo-corrected effect on systemic pulse oximetry was
      1.0% (95% confidence interval, -0.7 to 2.8), demonstrating that bosentan did not
      worsen oxygen saturation. Compared with placebo, bosentan reduced pulmonary
      vascular resistance index (-472.0 dyne.s.cm(-5); P=0.0383). The mean pulmonary
      arterial pressure decreased (-5.5 mm Hg; P=0.0363), and the exercise capacity
      increased (53.1 m; P=0.0079). Four patients discontinued as a result of adverse
      events, 2 (5%) in the bosentan group and 2 (12%) in the placebo group.
      CONCLUSIONS: In this first placebo-controlled trial in patients with Eisenmenger
      syndrome, bosentan was well tolerated and improved exercise capacity and
      hemodynamics without compromising peripheral oxygen saturation.

PMID- 16801460
TI  - Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in
      macrophages in vivo.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) in inflamed atherosclerotic plaques
      may contribute to extracellular matrix remodeling and the onset of acute
      thrombotic complications. METHODS AND RESULTS: To test the hypothesis that
      optical molecular imaging with the use of an activatable near-infrared
      fluorescence (NIRF) probe can detect enzymatic action of MMP in atherosclerotic
      plaques, we used a NIRF substrate for gelatinases (MMP-2/gelatinase-A and MMP
      9/gelatinase-B) in apolipoprotein E-deficient (apoE-/-) mice that consumed a high
      cholesterol diet for 12 weeks and age-matched apoE+/+ mice as control. The aortas
      of apoE-/- mice at 24 hours after probe yielded intense NIRF signals, as detected
      by NIRF reflectance ex vivo, compared with negligible signals in aortas of
      apoE+/+ mice with/without probe administration or atherosclerotic apoE-/- aortas
      without probe. Gelatinase inhibitor treatment abolished NIRF signals in apoE-/-
      mouse aortas ex vivo. Sites of gelatinase activity visualized by NIRF colocalized
      with macrophage accumulation, immunoreactive MMP-2 and MMP-9, and gelatinolytic
      activity detected by in situ zymography. Furthermore, fluorescence molecular
      tomography indicated in vivo that atherosclerotic aortas of apoE-/- mice produced
      NIRF signals for gelatinase action, whereas aortas of apoE+/+ mice injected with
      the probe or apoE-/- aortas with no probe exhibited negligible NIRF signals.
      CONCLUSIONS: These results suggest the feasibility of noninvasively imaging the
      enzymatic action of MMPs in vivo, an approach that may gauge inflammatory foci in
      atherosclerosis, assess cardiovascular risk, and evaluate the effects of
      therapeutic interventions.

PMID- 16801461
TI  - Effect of cardiac resynchronization on the incidence of atrial fibrillation in
      patients with severe heart failure.
AB  - BACKGROUND: Atrial fibrillation/flutter (AF) and heart failure often coexist;
      however, the effect of cardiac resynchronization therapy (CRT) on the incidence
      of AF and on the outcome of patients with new-onset AF remains undefined. METHODS
      AND RESULTS: In the CArdiac REsynchronisation in Heart Failure (CARE-HF) trial,
      813 patients with moderate or severe heart failure were randomly assigned to
      pharmacological therapy alone or with the addition of CRT. The incidence of AF
      was assessed by adverse event reporting and by ECGs during follow-up, and the
      impact of new-onset AF on the outcome and efficacy of CRT was evaluated. By the
      end of the study (mean duration of follow-up 29.4 months), AF had been documented
      in 66 patients in the CRT group compared with 58 who received medical therapy
      only (16.1% versus 14.4%; hazard ratio 1.05; 95% confidence interval, 0.73 to
      1.50; P=0.79). There was no difference in the time until first onset of AF
      between groups. Mortality was higher in patients who developed AF, but AF was not
      a predictor in the multivariable model (hazard ratio 1.17; 95% confidence
      interval, 0.82 to 1.67; P=0.37). In patients with new-onset AF, CRT significantly
      reduced the risk for all-cause mortality and all other predefined end points and
      improved ejection fraction and symptoms (no interaction between AF and CRT; all
      P>0.2). CONCLUSIONS: Although CRT did not reduce the incidence of AF, CRT
      improved the outcome regardless of whether AF developed.

PMID- 16801462
TI  - Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic
      resonance imaging is a powerful predictor of post-myocardial infarction
      mortality.
AB  - BACKGROUND: Accurate risk stratification is crucial for effective treatment
      planning after myocardial infarction (MI). Previous studies suggest that the peri
      infarct border zone may be an important arrhythmogenic substrate. In this pilot
      study, we tested the hypothesis that the extent of the peri-infarct zone
      quantified by contrast-enhanced cardiac magnetic resonance (CMR) is an
      independent predictor of post-MI mortality. METHODS AND RESULTS: We studied 144
      patients with documented coronary artery disease and abnormal myocardial delayed
      enhancement (MDE) consistent with MI. A computer-assisted, semiautomatic
      algorithm quantified the total infarct size and divided it into the core and peri
      infarct regions based on signal-intensity thresholds (>3 SDs and 2 to 3 SDs above
      remote normal myocardium, respectively). The peri-infarct zone was normalized as
      a percentage of the total infarct size (%MDE(periphery)). After a median follow
      up of 2.4 years, 29 (20%) patients died. Patients with an above-median
      %MDE(periphery) were at higher risk for death compared with those with a below
      median %MDE(periphery) (28% versus 13%, log-rank P<0.01). Multivariable analysis
      showed that left ventricular systolic volume index and %MDE(periphery) were the
      strongest predictors of all-cause mortality (adjusted hazard ratio [HR] for
      %MDE(periphery), 1.45 per 10% increase; P=0.002) and cardiovascular mortality
      (adjusted HR, 1.51 per 10% increase; P=0.009). Similarly, after adjusting for age
      and left ventricular ejection fraction, %MDE(periphery) maintained strong and
      independent associations with all-cause mortality (adjusted HR, 1.42; P=0.005)
      and cardiovascular mortality (adjusted HR, 1.49; P=0.01). CONCLUSIONS: In
      patients with a prior MI, the extent of the peri-infarct zone characterized by
      CMR provides incremental prognostic value beyond left ventricular systolic volume
      index or ejection fraction. Infarct characteristics by CMR may prove to be a
      unique and valuable noninvasive predictor of post-MI mortality.

PMID- 16801463
TI  - Cardiovascular outcomes with atrial-based pacing compared with ventricular
      pacing: meta-analysis of randomized trials, using individual patient data.
AB  - BACKGROUND: Several randomized trials have compared atrial-based (dual-chamber or
      atrial) pacing with ventricular pacing in patients with bradycardia. No trial has
      shown a mortality reduction, and only 1 small trial suggested a reduction in
      stroke. The goal of this review was to determine whether atrial-based pacing
      prevents major cardiovascular events. METHODS AND RESULTS: A systematic review
      was performed of publications since 1980. For inclusion, trials had to compare an
      atrial-based with a ventricular-based pacing mode; use a randomized, controlled,
      parallel design; and have data on mortality, stroke, heart failure, or atrial
      fibrillation. Individual patient data were obtained from 5 of the 8 identified
      studies, representing 95% of patients in the 8 trials, and a total of 35 000
      patient-years of follow-up. There was no significant heterogeneity among the
      results of the individual trials. There was no significant reduction in mortality
      (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87 to 1.03; P=0.19) or
      heart failure (HR, 0.89; 95% CI, 0.77 to 1.03; P=0.15) with atrial-based pacing.
      There was a significant reduction in atrial fibrillation (HR, 0.80; 95% CI, 0.72
      to 0.89; P=0.00003) and a reduction in stroke that was of borderline significance
      (HR, 0.81; 95% CI, 0.67 to 0.99; P=0.035). There was no convincing evidence that
      any patient subgroup received special benefit from atrial-based pacing.
      CONCLUSIONS: Compared with ventricular pacing, the use of atrial-based pacing
      does not improve survival or reduce heart failure or cardiovascular death.
      However, atrial-based pacing reduces the incidence of atrial fibrillation and may
      modestly reduce stroke.

PMID- 16801464
TI  - Routine thrombectomy in percutaneous coronary intervention for acute ST-segment
      elevation myocardial infarction: a randomized, controlled trial.
AB  - BACKGROUND: Distal embolization during primary percutaneous coronary intervention
      (PCI) for ST-elevation myocardial infarction may result in reduced myocardial
      perfusion, infarct extension, and impaired prognosis. METHODS AND RESULTS: In a
      prospective randomized trial, we studied the effect of routine thrombectomy in
      215 patients with ST-segment-elevation myocardial infarction lasting <12 hours
      undergoing primary PCI. Patients were randomized to thrombectomy pretreatment or
      standard PCI. The primary end point was myocardial salvage measured by sestamibi
      SPECT, calculated as the difference between area at risk and final infarct size
      determined after 30 days (percent). Secondary end points included final infarct
      size, ST-segment resolution, and troponin T release. Baseline variables,
      including ST-segment elevation and area at risk, were similar. Salvage was not
      statistically different in the thrombectomy and control groups (median, 13%
      [interquartile range, 9% to 21%] and 18% [interquartile range, 7% to 25%];
      P=0.12), but 24 patients in the thrombectomy group and 12 patients in the control
      group did not have an early SPECT scan, mainly because of poor general or cardiac
      condition (P=0.04). In the thrombectomy group, final infarct size was increased
      (median, 15%; [interquartile range, 4% to 25%] versus 8% [interquartile range, 2%
      to 18%]; P=0.004). CONCLUSIONS: Thrombectomy performed as routine therapy in
      primary PCI for ST-elevation myocardial infarction does not increase myocardial
      salvage. The study suggests a possible deleterious effect of thrombectomy,
      resulting in an increased final infarct size, and does not support the use of
      thrombectomy in unselected primary PCI patients.

PMID- 16801465
TI  - Renal function and effectiveness of angiotensin-converting enzyme inhibitor
      therapy in patients with chronic stable coronary disease in the Prevention of
      Events with ACE inhibition (PEACE) trial.
AB  - BACKGROUND: Patients with reduced renal function are at increased risk for
      adverse cardiovascular outcomes. In the post-myocardial infarction setting,
      angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective
      in patients with impaired renal function as in those with preserved renal
      function. METHODS AND RESULTS: We assessed the relation between renal function
      and outcomes, the influence of ACE inhibition on this relation, and whether renal
      function modifies the effectiveness of ACE inhibition in patients with stable
      coronary artery disease and preserved systolic function enrolled in the
      Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were
      randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical
      creatinine measures were available for 8280 patients before randomization. The
      estimated glomerular filtration rate (eGFR) was calculated with the 4-point
      Modification of Diet in Renal Disease equation. Renal function was related to
      outcomes, and the influence of ACE-inhibitor therapy was assessed with formal
      interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%)
      patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed
      a significant interaction between eGFR and treatment group with respect to
      cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with
      a reduction in total mortality in patients with reduced renal function (adjusted
      HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function
      (adjusted HR, 0.94; 95% CI, 0.78 to 1.13). CONCLUSIONS: Although trandolapril did
      not improve survival in the overall PEACE cohort, in which mean eGFR was
      relatively high, trandolapril reduced mortality in patients with reduced eGFR.
      These data suggest that reduced renal function may define a subset of patients
      most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.

PMID- 16801466
TI  - South Asians and cardiovascular risk: what clinicians should know.

PMID- 16801467
TI  - Images in cardiovascular medicine. Coronary-subclavian steal syndrome
      demonstrated by cardiovascular magnetic resonance.

PMID- 16801468
TI  - Images in cardiovascular medicine. Massive biventricular thrombosis as a
      consequence of myocarditis: findings from 2-dimensional and real-time 3
      dimensional echocardiography.

PMID- 16801469
TI  - Images in cardiovascular medicine. Transcatheter right ventricular outflow tract
      intervention: the risk to the coronary circulation.

PMID- 16801471
TI  - Viewpoint: megatrials and the development of antithrombotics.

PMID- 16801470
TI  - Letter by Saul and Haemmerich regarding article "Comparison of electrode cooling
      between internal and open irrigation in radiofrequency ablation lesion depth and
      incidence of thrombus and steam pop".

PMID- 16801472
TI  - Overcoming the defects of a virtue: dual-chamber versus single-chamber detection
      enhancements for implantable defibrillator rhythm diagnosis: the detect
      supraventricular tachycardia study.

PMID- 16801473
TI  - The aspirin resistance controversy: clinical entity or platelet heterogeneity?

PMID- 16801474
TI  - Vascular biomarkers and surrogates in cardiovascular disease.
AB  - Cardiovascular biomarker research efforts have resulted in the identification of
      new risk factors and novel drug targets, as well as the establishment of
      treatment guidelines. Government agencies, academic research institutions,
      diagnostic industries, and pharmaceutical companies all recognize the importance
      of biomarkers in advancing therapies to improve public health. In drug
      development, biomarkers are used to evaluate early signals of efficacy and
      safety, to select dose, and to identify the target population. The United States
      Food and Drug Administration has relied on biomarkers to support clinical
      applications in many therapeutic fields, including cardiovascular disease. The
      appropriate application of cardiovascular biomarkers requires an understanding of
      disease natural history, the mechanism of the intervention, and the
      characteristics and limitations of the biomarker. Channels of communication among
      researcher, developer, and regulator must remain open to maximize the success of
      future biomarker efforts. In 2003, 2004, and 2005, an international panel of
      cardiovascular biomarker experts convened at the "Cardiovascular Biomarker and
      Surrogate Endpoints Symposia" held in Bethesda, Md, to discuss the use of
      biomarkers in the development of improved cardiovascular diagnostics and
      therapeutics. The information presented in the present report summarizes the
      authors' perspective distilled from these proceedings.

PMID- 16801475
TI  - Preventing cardiovascular disease and diabetes: a call to action from the
      American Diabetes Association and the American Heart Association.

PMID- 16801477
TI  - Influence of saturated fat and linolenic acid on the association between intake
      of dairy products and blood pressure.
AB  - Data on the association between dairy consumption and blood pressure have been
      inconsistent. We sought to examine the relation between dairy consumption and
      prevalent hypertension (HTN) among 4797 participants of the National Heart, Lung,
      and Blood Institute Family Heart Study. We used generalized estimating equations
      to estimate prevalence odds ratios of HTN across categories of dairy consumption.
      From the lowest to the highest sex-, age-, and energy-adjusted quartile of dairy
      consumption, there was an inverse association between dairy intake and prevalent
      HTN: odds ratios (95% CIs) were 1.0 (reference), 0.82 (0.64 to 1.05), 0.68 (0.53
      to 0.89), and 0.62 (0.45 to 0.84), respectively, in a model adjusting for age,
      sex, energy intake, field center, body mass index, dietary linolenic acid,
      saturated and monounsaturated fat, sodium intake, potassium, caffeine, fiber, and
      fruits and vegetables (P for trend = 0.002). This association was independent of
      calcium intake and was mainly observed among subjects consuming fewer calories
      from saturated fat (P for interaction = 0.014). Dairy consumption was inversely
      associated with systolic (P for trend = 0.003) but not diastolic (P for trend =
      0.09) blood pressure. Although subjects consuming > or = 2 servings per day of
      dairy products and higher total linolenic acid had the lowest prevalence odds of
      HTN, there was no evidence for interaction between linolenic acid and dairy
      consumption on HTN (P for interaction = 0.65). In conclusion, our data indicate
      an inverse association between dairy consumption and prevalent HTN that was
      independent of dietary calcium, mainly among individuals consuming less saturated
      fat. This suggests that consumption of low-fat dairy products might be more
      beneficial for preventing HTN.

PMID- 16801478
TI  - Effects of a new hormone therapy, drospirenone and 17-beta-estradiol, in
      postmenopausal women with hypertension.
AB  - Drospirenone (DRSP), a progestin with antialdosterone activity, has been
      developed for hormone therapy in combination with 17-beta-estradiol (E2) in
      postmenopausal women. We evaluated the antihypertensive efficacy and safety of
      various doses of DRSP and E2 and estradiol alone in postmenopausal women with
      hypertension using ambulatory and clinic blood pressure (BP) monitoring. This was
      a randomized, double-blind clinical trial of 3 doses of DRSP combined with
      estradiol, estradiol alone, and placebo in 750 postmenopausal women with stage 1
      to 2 hypertension between 45 to 75 years. Ambulatory and clinic BPs, potassium,
      aldosterone, and lipid measurements and adverse events were evaluated in
      postmenopausal women with stages 1 to 2 hypertension during 8 weeks of double
      blind therapy. DRSP and E2 induced dose-related reductions in the ambulatory and
      clinic systolic BP with physiological increases in serum aldosterone. Significant
      decreases in 24-hour systolic pressure were observed at doses of 2 and 3 mg of
      DRSP combined with estradiol but not by estradiol alone or 1 mg of DRSP with
      estradiol. There were no significant changes from baseline in potassium in any
      treatment group. Small, significant reductions in total and low-density
      lipoprotein cholesterol occurred on all of the active treatments, and serum
      triglycerides did not change. Adverse event rates were low and similar across
      treatment groups. In conclusion, these data show that DRSP combined with E2
      significantly reduces BP in postmenopausal women with hypertension and did not
      induce significant increases in serum potassium. These characteristics may lead
      to a new benefit for this novel hormone therapy in postmenopausal women with
      hypertension.

PMID- 16801479
TI  - Thiazide-associated glucose abnormalities: prognosis, etiology, and prevention:
      is potassium balance the key?

PMID- 16801480
TI  - Development of hypertension and kidney hypertrophy in transgenic mice
      overexpressing ARAP1 gene in the kidney.
AB  - Angiotensin II regulates blood pressure via activation of the type 1 receptor. We
      previously identified a novel angiotensin II type 1 receptor-associated protein
      and demonstrated that it promotes receptor recycling to the plasma membrane. To
      delineate the pathophysiological function of the ARAP1 in the kidneys, we
      generated transgenic mice that overexpress rat ARAP1 cDNA specifically in
      proximal tubules and tested the hypothesis that proximal tubule-specific
      overexpression of ARAP1 causes hypertension. Two lines of male transgenic mice,
      650 and 670, displayed kidney-specific transgene expression. Systolic blood
      pressure was significantly elevated by &20 to 25 mm Hg in these lines of mice at
      20 weeks of age compared with their nontransgenic litter mates. Urine volume, but
      not water intake, was significantly decreased in both lines compared with
      nontransgenic controls. The kidney/body weight ratio was significantly increased
      in both lines compared with their nontransgenic litter mates at 12 and 20 weeks
      of age. In contrast, no difference was observed in the ratio of brain, spleen,
      heart, and testis to body weight between male transgenic and nontransgenic
      animals. Inhibitions of the renin-angiotensin system completely normalized the
      systolic blood pressure of transgenic mice. Moreover, low salt intake prevented
      the development of hypertension, whereas high salt intake exacerbated the
      increase in blood pressure in transgenic mice. Therefore, our data show that
      proximal tubule-specific overexpression of ARAP1 leads to hypertension,
      suggesting that renal ARAP1 plays an important role in the regulation of blood
      pressure and renal function via activation of the intrarenal renin-angiotensin
      system.

PMID- 16801481
TI  - Aldosterone, dietary salt, and renal disease.

PMID- 16801482
TI  - Renal damage in primary aldosteronism: results of the PAPY Study.
AB  - Primary aldosteronism (PA) has been associated with cardiovascular hypertrophy
      and fibrosis, in part independent of the blood pressure level, but deleterious
      effects on the kidneys are less clear. Likewise, it remains unknown if the kidney
      can be diversely involved in PA caused by aldosterone-producing adenoma (APA) and
      idiopathic hyperaldosteronism (IHA). Hence, in the Primary Aldosteronism
      Prevalence in Italy (PAPY) Study, a prospective survey of newly diagnosed
      consecutive patients referred to hypertension centers nationwide, we sought signs
      of renal damage in patients with PA and in comparable patients with primary
      hypertension (PH). Patients (n = 1180) underwent a predefined screening protocol
      followed by tests for confirming PA and identifying the underlying adrenocortical
      pathology. Renal damage was assessed by 24-hour urine albumin excretion (UAE)
      rate and glomerular filtration rate (GFR). UAE rate was measured in 490 patients;
      all had a normal GFR. Of them, 31 (6.4%) had APA, 33 (6.7%) had IHA, and the rest
      (86.9%) had PH. UAE rate was predicted (P < 0.001) by body mass index, age,
      urinary Na+ excretion, serum K+, and mean blood pressure. Covariate-adjusted UAE
      rate was significantly higher in APA and IHA than in PH patients; there were more
      patients with microalbuminuria in the APA and IHA than in the PH group (P =
      0.007). Among the hypertensive patients with a preserved GFR, those with APA or
      IHA have a higher UAE rate than comparable PH patients. Thus, hypertension
      because of excess autonomous aldosterone secretion features an early and more
      prominent renal damage than PH.

PMID- 16801483
TI  - Clarifying endothelin type B receptor function.

PMID- 16801484
TI  - Deletion of endothelial cell endothelin B receptors does not affect blood
      pressure or sensitivity to salt.
AB  - Endothelin B receptors in different tissues regulate diverse physiological
      responses including vasoconstriction, vasodilatation, clearance of endothelin-1,
      and renal tubular sodium reabsorption. To examine the role of endothelial cell
      endothelin B receptors in these processes, we generated endothelial cell-specific
      endothelin B receptor knockout mice using a Cre-loxP approach. We have
      demonstrated loss of endothelial cell endothelin B receptor expression and
      function and preservation of nonendothelial endothelin B receptor-mediated
      responses through binding and functional assays. Ablation of endothelin B
      receptors exclusively from endothelial cells produces endothelial dysfunction in
      the absence of hypertension, with evidence of decreased endogenous release of NO
      and increased plasma endothelin-1. In contrast to models of total endothelin B
      receptor ablation, the blood pressure response to a high-salt diet is unchanged
      in endothelial cell-specific endothelin B receptor knockouts compared with
      control floxed mice. These findings suggest that the endothelial cell endothelin
      B receptor mediates a tonic vasodilator effect and that nonendothelial cell
      endothelin B receptors are important for the regulation of blood pressure.

PMID- 16801485
TI  - Differentiation of cyclooxygenase 1- and 2-derived prostanoids in mouse kidney
      and aorta.
AB  - Accumulating evidence indicates cyclooxygenase (COX) 1 and COX2 differentially
      regulate cardiovascular and renal function. We have demonstrated previously in
      mice that COX2 inhibition enhances angiotensin II-induced hypertension, and COX1
      inhibition attenuates the pressor effect of angiotensin II. To further elucidate
      the mechanism underlying the functional difference of COX1 versus COX2
      inhibition, the present studies examined the prostaglandin (PG) profiles derived
      in COX1- or COX2-inhibited mouse kidney and aorta using gas chromatographic/mass
      spectrometric assays. PGE2 is the most abundant prostanoid in both renal cortex
      and medulla in normal C57BL/6J mice, followed by PGI2, PGF2alpha and thromboxane
      A2. In contrast PGI2 was most abundant in aorta followed by thromboxane A2, PGE2,
      and PGF2alpha. PGD2 was undetectable in control kidney or aorta. At baseline,
      inhibition of COX1 decreased total prostaglandins in renal cortex, medulla, and
      aorta, whereas COX2 inhibition decreased total prostaglandins only in renal
      medulla. Angiotensin II infusion significantly increased COX2-dependent/COX1
      independent PGE2 and PGI2 in renal cortex and medulla. Angiotensin II also
      significantly increased renal PGF2alpha in cortex, but not in medulla, through
      both COX1- and COX2-dependent mechanisms. These studies demonstrate that although
      COX1 primarily contributes to basal prostanoid production in the kidney and
      aorta, angiotensin II increases renal vasodilator prostanoids predominately via
      COX2 activity. These effects may contribute to the specific effect of COX2
      inhibitors to increase blood pressure.

PMID- 16801487
TI  - Are narrower or wider retinal venules associated with incident hypertension?

PMID- 16801488
TI  - Thiazide diuretics, potassium, and the development of diabetes: a quantitative
      review.
AB  - National guidelines and a recent clinical trial have supported the use of
      thiazide diuretics as the preferred initial pharmacological treatment for
      hypertension. However, evidence from this and other clinical trials have also
      found an increased incidence of new onset diabetes among those patients receiving
      thiazide diuretics. The mechanisms responsible for the increased incidence of
      diabetes with thiazide diuretics have not been fully elucidated. This article
      provides a review of intervention studies that included data on the relation
      between thiazide-induced hypokalemia and glucose intolerance. We conducted a
      literature search from 1966 to June 2004 to identify clinical trials using
      thiazide diuretics where the metabolic effects on potassium and glucose are
      reported. A total of 59 clinical trials constituting 83 thiazide diuretic study
      arms were identified. Trial size, length, type of thiazide diuretic, and dose
      varied substantially among the studies. The association between average changes
      in potassium and glucose in the study arms is considered jointly in a weighted
      statistical model. The Pearson's correlation coefficient, weighted by study
      sample size, for the relationship between glucose and potassium was -0.54 (95%
      CI, -0.67 to -0.36; P < 0.01). A sensitivity analysis, which considered subset
      analyses and effect of covariates, as well as inverse-variance weighting,
      supported this finding. These data suggest that thiazide-induced hypokalemia is
      associated with increased blood glucose. Treatment of thiazide-induced
      hypokalemia may reverse glucose intolerance and possibly prevent the future
      development of diabetes.

PMID- 16801489
TI  - Adverse effects of cigarette smoke on NO bioavailability: role of arginine
      metabolism and oxidative stress.
AB  - Endothelial dysfunction is a hallmark of cardiovascular disease, and the l
      arginine:NO pathway plays a critical role in determining endothelial function.
      Recent studies suggest that smoking, a well-recognized risk factor for vascular
      disease, may interfere with l-arginine and NO metabolism; however, this remains
      poorly characterized. Accordingly, we performed a series of complementary in vivo
      and in vitro studies to elucidate the mechanism by which cigarette smoke
      adversely affects endothelial function. In current smokers, plasma levels of
      asymmetrical dimethyl-arginine (ADMA) were 80% higher (P = 0.01) than nonsmokers,
      whereas citrulline (17%; P < 0.05) and N-hydroxy-l-arginine (34%; P < 0.05) were
      significantly lower. Exposure to 10% cigarette smoke extract (CSE) significantly
      affected endothelial arginine metabolism with reductions in the intracellular
      content of citrulline (81%), N-hydroxy-l-arginine (57%), and arginine (23%),
      while increasing ADMA (129%). CSE significantly inhibited (38%) arginine uptake
      in conjunction with a 34% reduction in expression of the arginine transporter,
      CAT1. In conjunction with these studies, CSE significantly reduced the activity
      of eNOS and NO production by endothelial cells, while stimulating the production
      of reactive oxygen species. In conclusion, cigarette smoke adversely affects the
      endothelial l-arginine NO synthase pathway, resulting in reducing NO production
      and elevated oxidative stress. In conjunction, exposure to cigarette smoke
      increases ADMA concentration, the latter being a risk factor for cardiovascular
      disease.

PMID- 16801490
TI  - Circulating microparticles: a potential prognostic marker for atherosclerotic
      vascular disease.

PMID- 16801493
TI  - Molecular mechanisms of memory storage in Aplysia.
AB  - Cellular studies of implicit and explicit memory suggest that experience
      dependent modulation of synaptic strength and structure is a fundamental
      mechanism by which these memories are encoded, processed, and stored within the
      brain. In this review, we focus on recent advances in our understanding of the
      molecular mechanisms that underlie short-term, intermediate-term, and long-term
      forms of implicit memory in the marine invertebrate Aplysia californica, and
      consider how the conservation of common elements in each form may contribute to
      the different temporal phases of memory storage.

PMID- 16801494
TI  - Signaling to the enemy? Body pattern expression and its response to external cues
      during hunting in the cuttlefish Sepia officinalis (Cephalopoda).
AB  - Cuttlefish can rapidly alter their appearance by using neurally controlled
      chromatophore organs. This ability may provide a window into their cognitive
      capacity. We test whether the changes in body pattern that occur during hunting
      depend on context. If they do, then it may be possible to use these changes to
      study cephalopod cognition while the animal is engaged in ecologically relevant
      tasks. We found consistent individual differences in the tendency of cuttlefish
      to hunt with the first two arms raised. We also found that cuttlefish usually
      darken their skin after they seize a prey item. This darkening is observed
      regardless of the identity of the prey (fish, crab, or shrimp), prey context
      (buried in sand, in a bare tank, or on top of a rock pile), or the presence of a
      sudden stimulus. The sudden stimulus was created by presenting an overhead model
      bird to the cuttlefish. The model induced components of the Deimatic Display,
      which is a form of antipredator behavior, suggesting that the model was perceived
      as a potential threat. Passing Cloud displays and the Darkening of the arms were
      significantly reduced after exposure to the model bird. The effect of a potential
      predator on body pattern expression during hunting suggests it may be possible to
      use these changes as a sensitive indicator of ecologically relevant learning.

PMID- 16801495
TI  - Bryostatin enhancement of memory in Hermissenda.
AB  - Bryostatin, a potent agonist of protein kinase C (PKC), when administered to
      Hermissenda was found to affect acquisition of an associative learning paradigm.
      Low bryostatin concentrations (0.1 to 0.5 ng/ml) enhanced memory acquisition,
      while concentrations higher than 1.0 ng/ml down-regulated the pathway and no
      recall of the associative training was exhibited. The extent of enhancement
      depended upon the conditioning regime used and the memory stage normally fostered
      by that regime. The effects of two training events (TEs) with paired conditioned
      and unconditioned stimuli, which standardly evoked only short-term memory (STM)
      lasting 7 min, were--when bryostatin was added concurrently--enhanced to a long
      term memory (LTM) that lasted about 20 h. The effects of both 4- and 6-paired TEs
      (which by themselves did not generate LTM), were also enhanced by bryostatin to
      induce a consolidated memory (CM) that lasted at least 5 days. The standard
      positive 9-TE regime typically produced a CM lasting at least 6 days. Low
      concentrations of bryostatin (<0.5 ng/ml) elicited no demonstrable enhancement of
      CM from 9-TEs. However, animals exposed to bryostatin concentrations higher than
      1.0 ng/ml exhibited no behavioral learning. Sharp-electrode intracellular
      recordings of type-B photoreceptors in the eyes from animals conditioned in vivo
      with bryostatin revealed changes in input resistance and an enhanced long-lasting
      depolarization (LLD) in response to light. Likewise, quantitative
      immunocytochemical measurements using an antibody specific for the PKC-activated
      Ca2+/GTP-binding protein calexcitin showed enhanced antibody labeling with
      bryostatin. Animals exposed to the PKC inhibitor bisindolylmaleimide-XI (Ro-32
      0432) administered by immersion prior to 9-TE conditioning showed no training
      induced changes with or without bryostatin exposure. However, if animals received
      bryostatin before Ro-32, the enhanced acquisition and demonstrated recall still
      occurred. Therefore, pathways responsible for the enhancement effects induced by
      bryostatin were putatively mediated by PKC. Overall, the data indicated that PKC
      activation occurred and calexcitin levels were raised during the acquisition
      phases of associative conditioning and memory initiation, and subsequently
      returned to baseline levels within 24 and 48 h, respectively. Therefore, the
      protracted recall measured by the testing regime used was probably due to
      bryostatin-induced changes during the acquisition and facilitated storage of
      memory, and not necessarily to enhanced recall of the stored memory when tested
      many days after training.

PMID- 16801496
TI  - Target-specific regulation of synaptic efficacy in the feeding central pattern
      generator of Aplysia: potential substrates for behavioral plasticity?
AB  - The contributions to this symposium are unified by their focus on the role of
      synaptic plasticity in sensorimotor learning. Synaptic plasticities are also
      known to operate within the central pattern generator (CPG) circuits that produce
      repetitive motor programs, where their relation to adaptive behavior is less well
      understood. This study examined divergent synaptic plasticity in the signaling of
      an influential interneuron, B20, located within the CPG that controls
      consummatory feeding-related behaviors in Aplysia. Previously, B20 was shown to
      contain markers for catecholamines and GABA (Diaz-Rios et al., 2002), and its
      rapid synaptic signaling to two follower motor neurons, B16 and B8, was found to
      be mediated by dopamine (Diaz-Rios and Miller, 2005). In this investigation, two
      incremental forms of increased synaptic efficacy, facilitation and summation,
      were both greater in the signaling from B20 to B8 than in the signaling from B20
      to B16. Manipulation of the membrane potentials of the two postsynaptic motor
      neurons did not affect facilitation of excitatory postsynaptic potentials (EPSPs)
      to either follower cell. Striking levels of summation in B8, however, were
      eliminated at hyperpolarized membrane potentials and could be attributed to
      distinctive membrane properties of this postsynaptic cell. GABA and the GABAB
      agonist baclofen increased facilitation and summation of EPSPs from B20 to B8,
      but not to B16. The enhanced facilitation was not affected when the membrane
      potential of B8 was pre-set to hyperpolarized levels, but GABAergic effects on
      summation were eliminated by this manipulation. These observations demonstrate a
      target-specific amplification of synaptic efficacy that can contribute to
      channeling the flow of divergent information from an intrinsic interneuron within
      the buccal CPG. They further suggest that GABA, acting as a cotransmitter in B20,
      could induce coordinated and target-specific pre- and postsynaptic modulation of
      these signals. Finally, we speculate that target-specific plasticity and its
      modulation could be efficient, specific, and flexible substrates for learning
      related modifications of CPG function.

PMID- 16801497
TI  - Long-term habituation in the marine mollusc Tritonia diomedea.
AB  - Tritonia diomedea is one of several gastropod molluscs used to study cellular
      mechanisms of learning and memory. Previous studies in this organism have focused
      on short-term habituation and sensitization. This report presents the first
      detailed description of long-term habituation in Tritonia. Experimental animals
      were given 11 swim sessions, each consisting of 10 trials, over 6 days, during
      which they typically displayed an initial sensitization, followed by short-term,
      within-session habituation. Responses were compared to controls, which were given
      a single stimulus per day. Cycle number habituation steadily accumulated over the
      days of training, and then persisted for at least 2 days after the end of
      training. These findings will permit comparative studies of the cellular
      mechanisms of short- and long-term memory in this highly tractable model system.

PMID- 16801498
TI  - Essential role of somatic and synaptic protein synthesis and axonal transport in
      long-term synapse-specific facilitation at distal sensorimotor connections in
      Aplysia.
AB  - To investigate further the cellular mechanisms underlying long-term facilitation
      (LTF) and long-term synapse-specific facilitation (LTSSF), we studied the role of
      axonal transport and somatic and synaptic protein synthesis at proximal and
      distal synapses of Aplysia siphon sensory neurons (SNs). The long soma-synapse
      distances (2.5 to 3 cm) of the SN distal synapses impose important temporal and
      mechanistic constraints on long-term facilitation and on intracellular signaling.
      Excitatory postsynaptic potentials (EPSPs) evoked by SNs in central and
      peripheral siphon motor neurons were used to assay LTF 24-30 h after various
      pharmacological treatments. Inhibition of protein synthesis via anisomycin
      application at either the SN soma or distal synapses blocked the induction of LTF
      and LTSSF normally produced by synaptic application of the facilitating
      transmitter serotonin (5-hydroxytryptamine). Further, disruption of axonal
      transport by application of nocodazole to the isolated siphon nerve completely
      blocked LTF at distal synapses. These results indicate an essential role for
      somatic and synaptic protein synthesis and active axonal transport in LTSSF at
      distal synapses, and raise intriguing questions for current synaptic
      marking/capture models of synapse specificity and LTF.

PMID- 16801499
TI  - Molecular characterization of NMDA-like receptors in Aplysia and Lymnaea:
      relevance to memory mechanisms.
AB  - The N-methyl-D-aspartate (NMDA) receptor belongs to the group of ionotropic
      glutamate receptors and has been implicated in synaptic plasticity, memory
      acquisition, and learning in both vertebrates and invertebrates, including
      molluscs. However, the molecular identity of NMDA-type receptors in molluscs
      remains unknown. Here, we cloned two NMDA-type receptors from the sea slug
      Aplysia californica, AcNR1-1 and AcNR1-2, as well as their homologs from the
      freshwater pulmonate snail Lymnaea stagnalis, LsNR1-1 and LsNR1-2. The cloned
      receptors contain a signal peptide, two extracellular segments with predicted
      binding sites for glycine and glutamate, three recognized transmembrane regions,
      and a fourth hydrophobic domain that makes a hairpin turn to form a pore-like
      structure. Phylogenetic analysis suggests that both the AcNR1s and LsNR1s belong
      to the NR1 subgroup of ionotrophic glutamate receptors. Our in situ hybridization
      data indicate highly abundant, but predominantly neuron-specific expression of
      molluscan NR1-type receptors in all central ganglia, including identified motor
      neurons in the buccal and abdominal ganglia as well as groups of mechanosensory
      cells. AcNR1 transcripts were detected extrasynaptically in the neurites of
      metacerebral cells of Aplysia. The widespread distribution of AcNR1 and LsNR1
      transcripts also implies diverse functions, including their involvement in the
      organization of feeding, locomotory, and defensive behaviors.

PMID- 16801500
TI  - The cellular mechanisms of learning in Aplysia: of blind men and elephants.
AB  - Until recently, investigations of the neurobiological substrates of simple forms
      of learning and memory in the marine snail Aplysia have focused mostly on plastic
      changes that occur within the presynaptic sensory neurons. Here, I summarize the
      results of recent studies that indicate that exclusively presynaptic processes
      cannot account for simple forms of learning in Aplysia. In particular, I present
      evidence that postsynaptic mechanisms play a far more important role in
      nonassociative learning in Aplysia than has been appreciated before now.
      Moreover, I describe recent data that suggests the intriguing hypothesis that the
      persistent, learning-induced changes in Aplysia sensory neurons might depend
      critically on postsynaptic signals for their induction. Finally, I discuss the
      potential applicability of this hypothesis to learning-related synaptic
      plasticity in the mammalian brain.

PMID- 16801501
TI  - Lessons from a crab: molecular mechanisms in different memory phases of
      Chasmagnathus.
AB  - Consolidation of long-term memory requires the activation of several transduction
      pathways that lead to post-translational modifications of synaptic proteins and
      to regulation of gene expression, both of which promote stabilization of specific
      changes in the activated circuits. In search of the molecular mechanisms involved
      in such processes, we used the context-signal associative learning paradigm of
      the crab Chasmagnathus. In this model, we studied the role of some molecular
      mechanisms, namely cAMP-dependent protein kinase (PKA), extracellular-signal
      regulated kinase (ERK), the nuclear factor kappa B (NF-kappaB) transcription
      factor, and the role of synaptic proteins such as amyloid beta precursor protein,
      with the object of describing key mechanisms involved in memory processing. In
      this article we review the most salient results obtained over a decade of
      research in this memory model.

PMID- 16801502
TI  - Pavlovian conditioning in Hermissenda: a circuit analysis.
AB  - An understanding of associative learning requires (1) an adequate description of
      the experimental conditions under which learning is produced, (2) a knowledge of
      what is learned or the determination of the content of learning, and (3) an
      explanation of how learning generates changes in behavior (Rescorla, 1980). These
      basic issues are being addressed at both the behavioral and cellular/molecular
      levels by the analysis of associative learning in animals with relatively
      uncomplex nervous systems. Use of Pavlovian conditioning of invertebrates as a
      model for associative learning has led to the identification of cellular and
      synaptic mechanisms underlying the formation of basic associations. However, an
      understanding of the associative processes that form the basis for Pavlovian
      conditioning requires an explanation not only of the mechanisms of temporal
      contiguity or predictability between the conditioned stimulus (CS) and the
      unconditioned stimulus (US), but also of how changes produced in the nervous
      system by conditioning are expressed in behavior. Studies with invertebrates have
      provided the opportunity to examine how associative learning is expressed in the
      neural circuitry that supports the generation of learned behavior.

PMID- 16801503
TI  - Comparative study of visuo-vestibular conditioning in Lymnaea stagnalis.
AB  - In this review, we compare the current understanding of visuo-vestibular
      conditioning in Hermissenda crassicornis and Lymnaea stagnalis on the basis of
      behavioral, electrophysiologic, and morphologic studies. Paired presentation of a
      photic conditioned stimulus (CS) and an orbital rotation unconditioned stimulus
      (US) results in conditioned escape behavior in both species. In Hermissenda,
      changes in excitability of type B photoreceptors and morphologic modifications at
      the axon terminals follow conditioning. Caudal hair cells, which detect
      mechanical turbulence, have reciprocal inhibition with type B photoreceptors. In
      Lymnaea, the interaction between photoreceptors and hair cells is dependent on
      statocyst location. Furthermore, the organization of the Lymnaea eye is complex,
      with more than 100 photoreceptors distributed in a uniquely folded retina.
      Although the optimal conditions to produce long-term memory (memory persistent
      for >1 week) are almost identical in Hermissenda and Lymnaea, physiologic and
      morphologic differences suggest that the neuronal mechanisms underlying learning
      and memory are distinct.

PMID- 16801504
TI  - The octopus: a model for a comparative analysis of the evolution of learning and
      memory mechanisms.
AB  - Comparative analysis of brain function in invertebrates with sophisticated
      behaviors, such as the octopus, may advance our understanding of the evolution of
      the neural processes that mediate complex behaviors. Until the last few years,
      this approach was infeasible due to the lack of neurophysiological tools for
      testing the neural circuits mediating learning and memory in the brains of
      octopus and other cephalopods. Now, for the first time, the adaptation of modern
      neurophysiological methods to the study of the central nervous system of the
      octopus allows this avenue of research. The emerging results suggest that a
      convergent evolutionary process has led to the selection of vertebrate-like
      neural organization and activity-dependent long-term synaptic plasticity. As
      octopuses and vertebrates are very remote phylogenetically, this convergence
      suggests the importance of the shared properties for the mediation of learning
      and memory.

PMID- 16801505
TI  - Squid (Loligo pealei) giant fiber system: a model for studying neurodegeneration
      and dementia?
AB  - In many neurodegenerative disorders that lead to memory loss and dementia, the
      brain pathology responsible for neuronal loss is marked by accumulations of
      proteins in the form of extracellular plaques and intracellular filamentous
      tangles, containing hyperphosphorylated cytoskeletal proteins. These are assumed
      to arise as a consequence of deregulation of a normal pattern of topographic
      phosphorylation-that is, an abnormal shift of cytoskeletal protein
      phosphorylation from the normal axonal compartment to cell bodies. Although
      decades of studies have been directed to this problem, biochemical approaches in
      mammalian systems are limited: neurons are too small to permit separation of cell
      body and axon compartments. Since the pioneering studies of Hodgkin and Huxley on
      the giant fiber system of the squid, however, the stellate ganglion and its giant
      axons have been the focus of a large literature on the physiology and
      biochemistry of neuron function. This review concentrates on a host of studies in
      our laboratory and others on the factors regulating compartment-specific patterns
      of cytoskeletal protein phosphorylation (primarily neurofilaments) in an effort
      to establish a normal baseline of information for further studies on
      neurodegeneration. On the basis of these data, a model of topographic regulation
      is proposed that offers several possibilities for further studies on potential
      sites of deregulation that may lead to pathologies resembling those seen in
      mammalian and human brains showing neurodegeneration, dementia, and neuronal cell
      death.

PMID- 16801507
TI  - Vitamin K and the prevention of fractures: systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Observational and some experimental data suggest that low intake of
      vitamin K may be associated with an increased risk of fracture. OBJECTIVE: To
      assess whether oral vitamin K (phytonadione and menaquinone) supplementation can
      reduce bone loss and prevent fractures. DATA SOURCES: The search included the
      following electronic databases: MEDLINE (1966 to June 2005), EMBASE (1980 to June
      2005), the Cochrane Library (issue 2, 2005), the ISI Web of Science (1945 to June
      2005), the National Research Register (inception to the present), Current
      Controlled Trials, and the Medical Research Council Research Register. STUDY
      SELECTION: Randomized controlled trials that gave adult participants oral
      phytonadione and menaquinone supplements for longer than 6 months were included
      in this review. DATA EXTRACTION: Four authors extracted data on changes in bone
      density and type of fracture. All articles were double screened and double data
      extracted. DATA SYNTHESIS: Thirteen trials were identified with data on bone
      loss, and 7 reported fracture data. All studies but 1 showed an advantage of
      phytonadione and menaquinone in reducing bone loss. All 7 trials that reported
      fracture effects were Japanese and used menaquinone. Pooling the 7 trials with
      fracture data in a meta-analysis, we found an odds ratio (OR) favoring
      menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral
      fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19
      (95% CI, 0.11-0.35) for all nonvertebral fractures. CONCLUSIONS: This systematic
      review suggests that supplementation with phytonadione and menaquinone-4 reduces
      bone loss. In the case of the latter, there is a strong effect on incident
      fractures among Japanese patients.

PMID- 16801508
TI  - Severe hot flashes are associated with chronic insomnia.
AB  - BACKGROUND: Because hot flashes can occur during the night, their presence has
      been frequently associated with insomnia in women with symptoms of menopause.
      However, many factors other than hot flashes or menopause can be responsible for
      insomnia, and several factors associated with insomnia in the general population
      are also commonly observed in perimenopausal and postmenopausal women who have
      hot flashes. METHODS: A random sample of 3243 subjects (aged > or =18 years)
      representative of the California population was interviewed by telephone.
      Included were 982 women aged 35 to 65 years. Women were divided into 3 groups
      according to menopausal status: premenopause (57.2%), perimenopause (22.3%), and
      postmenopause (20.5%). Hot flashes were counted if they were present for at least
      3 days per week during the last month and were classified as mild, moderate, or
      severe according to their effect on daily functioning. Chronic insomnia was
      defined as global sleep dissatisfaction, difficulty initiating sleep, difficulty
      maintaining sleep, or nonrestorative sleep, for at least 6 months. Diagnoses of
      insomnia were assessed according to the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, classification. RESULTS: Prevalence of hot
      flashes was 12.5% in premenopause, 79.0% in perimenopause, and 39.3% in
      postmenopause. Prevalence of chronic insomnia was reported as 36.5% in
      premenopause, 56.6% in perimenopause, and 50.7% in postmenopause (P<.001).
      Prevalence of symptoms of chronic insomnia increased with the severity of hot
      flashes, reaching more than 80% in perimenopausal women and postmenopausal women
      who had severe hot flashes. In multivariate analyses, severe hot flashes were
      significantly associated with symptoms and a diagnosis of chronic insomnia. Poor
      health, chronic pain, and sleep apnea were other significant factors associated
      with chronic insomnia. CONCLUSIONS: Severe hot flashes are strongly associated
      with chronic insomnia in midlife women. The presence of hot flashes should be
      systematically investigated in women with insomnia. Treating hot flashes could
      improve sleep quality and minimize the deleterious consequences of chronic
      insomnia.

PMID- 16801509
TI  - Mixed comparison of stroke prevention treatments in individuals with nonrheumatic
      atrial fibrillation.
AB  - BACKGROUND: We aimed to identify different stroke prevention treatments for
      atrial fibrillation assessed in randomized controlled trials and to compare them
      within a single evidence synthesis framework. METHODS: We updated the Cochrane
      review on anticoagulants and antiplatelet therapy for nonrheumatic atrial
      fibrillation to include randomized controlled trials published between January
      2000 and March 2005 identified via the CENTRAL database and MEDLINE. A mixed
      treatment comparison method was used to combine direct within-trial, between
      treatment comparisons with indirect trial evidence while maintaining
      randomization. RESULTS: Data were combined from 19 clinical trials that included
      17 833 patients randomized to 9 treatment strategies, including placebo. For
      prevention of ischemic stroke, adjusted standard-dose warfarin sodium (relative
      rate [RR], 0.35; 95% credible interval [CrI], 0.24 to 0.52), adjusted low-dose
      warfarin (RR, 0.35; 95% CrI, 0.19 to 0.60), ximelagatran (RR, 0.34; 95% CrI, 0.18
      to 0.61), and aspirin (RR, 0.64; 95% CrI, 0.44 to 0.88) were all associated with
      a significantly lower rate of ischemic stroke compared with placebo. For major
      and fatal bleeding episodes, there was some evidence of an increased risk for all
      treatments but none were statistically significant. Assuming a baseline risk of
      51 ischemic stroke events per 1000 person-years, it can be estimated that
      adjusted standard-dose warfarin could prevent 28 (95% CrI, -37 to -19) ischemic
      strokes at the expense of 11 (95% CrI, -1 to +39) major or fatal bleeding
      episodes. In comparison, aspirin could prevent 16 (95% CrI, -26 to -5) ischemic
      strokes at the expense of 6 (95% CrI, -3 to +27) major or fatal bleeding
      episodes. CONCLUSIONS: A lower rate of ischemic stroke and a higher rate of major
      bleeding episodes were found to be associated with oral anticoagulants compared
      with aspirin, and both anticoagulants and aspirin were found to be associated
      with a reduction in the rate of stroke compared with placebo.

PMID- 16801510
TI  - Drug-induced long QT syndrome in injection drug users receiving methadone: high
      frequency in hospitalized patients and risk factors.
AB  - BACKGROUND: Drug-induced long QT syndrome is a serious adverse drug reaction.
      Methadone prolongs the QT interval in vitro in a dose-dependent manner. In the
      inpatient setting, the frequency of QT interval prolongation with methadone
      treatment, its dose dependence, and the importance of cofactors such as drug-drug
      interactions remain unknown. METHODS: We performed a systematic, retrospective
      study comparing active or former intravenous drug users receiving methadone and
      those not receiving methadone among all patients hospitalized over a 5-year
      period in a tertiary care hospital. A total of 167 patients receiving methadone
      fulfilled the inclusion criteria and were compared with a control group of 80
      injection drug users not receiving methadone. In addition to methadone dose, 15
      demographic, biological, and pharmacological variables were considered as
      potential risk factors for QT prolongation. RESULTS: Among 167 methadone
      maintenance patients, the prevalence of QTc prolongation to 0.50 second((1/2)) or
      longer was 16.2% compared with 0% in 80 control subjects. Six patients (3.6%) in
      the methadone group presented torsades de pointes. QTc length was weakly but
      significantly associated with methadone daily dose (Spearman rank correlation
      coefficient, 0.20; P<.01). Multivariate regression analysis allowed attribution
      of 31.8% of QTc variability to methadone dose, cytochrome P-450 3A4 drug-drug
      interactions, hypokalemia, and altered liver function. CONCLUSIONS: QT interval
      prolongation in methadone maintenance patients hospitalized in a tertiary care
      center is a frequent finding. Methadone dose, presence of cytochrome P-450 3A4
      inhibitors, potassium level, and liver function contribute to QT prolongation.
      Long QT syndrome can occur with low doses of methadone.

PMID- 16801511
TI  - Reemergence of gram-negative health care-associated bloodstream infections.
AB  - BACKGROUND: Primary health care-associated bloodstream infections (PHA-BSIs)
      affect as many as 350 000 patients in the United States annually. Whereas gram
      negative organisms were the leading cause before the 1970s, gram-positive
      organisms have been the predominant microbial isolates since then. METHODS: We
      identified all PHA-BSIs among adult inpatients in a 625-bed quaternary care
      hospital from January 1, 1996, through December 31, 2003, and evaluated trends in
      the microbial etiology, geographic distribution within the institution, and
      antimicrobial susceptibilities. RESULTS: A total of 3662 PHA-BSIs caused by 4349
      bacterial and fungal isolates were identified. From 1999 to 2003, the proportion
      of PHA-BSIs due to gram-negative organisms increased from 15.9% to 24.1% (P<.001
      for trend). This trend was not significantly different across various units of
      the hospital, and no specific gram-negative species contributed
      disproportionately to the increase. With few exceptions, there were no
      significant increases in antimicrobial resistance. The increase in gram-negative
      organisms was accompanied by a decline in the proportion of PHA-BSIs from
      coagulase-negative staphylococci (from 33.5% in 1999 to 29.9% in 2003, P = .007)
      and from Staphylococcus aureus (from 18.8% in 1999 to 11.8% in 2003, P = .004).
      The proportion of PHA-BSIs from Candida species almost doubled from 5.8% in 1999
      to 11.3% in 2003 (P = .002). CONCLUSIONS: To our knowledge, this is the first US
      study to report a reemergence of gram-negative organisms as a cause of PHA-BSIs.
      This finding does not seem to be related to changes in specific gram-negative
      organisms or to antimicrobial resistance. If this trend continues, it will have
      important implications for the management of bloodstream infections.

PMID- 16801512
TI  - Potentially modifiable resident characteristics that are associated with physical
      or verbal aggression among nursing home residents with dementia.
AB  - BACKGROUND: Physical aggression by nursing home residents is a burden to
      residents and staff. The identification of modifiable correlates would facilitate
      developing preventive strategies. The objectives of the study were to determine
      potentially modifiable resident characteristics that are associated with physical
      aggression and to correlate these characteristics with verbal aggression.
      METHODS: This was a cross-sectional study of nursing home residents in 5 states
      who had at least 1 annual Minimum Data Set assessment completed during 2002. Case
      subjects were defined as nursing home residents 60 years and older with dementia
      who were reported to have been physically aggressive in the week before their
      assessment. Control subjects were all other residents 60 years and older with
      dementia. The main outcome measure was being physically aggressive during the
      past week. RESULTS: A total of 103 344 residents met study criteria, of whom 7120
      (6.9%) had been physically aggressive in the week before their annual Minimum
      Data Set assessment. After adjustment for potential confounders, including age,
      sex, severity of cognitive impairment, and dependence in activities of daily
      living, physical aggression was associated with depressive symptoms (adjusted
      odds ratio [AOR], 3.3; 99% confidence interval [CI], 3.0-3.6), delusions (AOR,
      2.0; 99% CI, 1.7-2.4), hallucinations (AOR, 1.4; 99% CI, 1.1-1.8), and
      constipation (AOR, 1.3; 99% CI, 1.2-1.5). Urinary tract infections, respiratory
      tract infections, fevers, reported pain, and participation in recreational
      activities were not significantly associated with physical aggression in
      multivariate analyses (P >.01 for all). Except for constipation, the correlates
      of verbal aggression were similar to those of physical aggression. CONCLUSION: If
      the associations we have estimated are causal, then treatment of depression,
      delusions, hallucinations, and constipation may reduce physical aggression among
      nursing home residents.

PMID- 16801513
TI  - No association between immunization and Guillain-Barre syndrome in the United
      Kingdom, 1992 to 2000.
AB  - BACKGROUND: Our goal was to determine whether immunization is associated with the
      incidence of Guillain-Barre syndrome (GBS). METHODS: We analyzed data for all
      patients registered with 253 general practices in the United Kingdom General
      Practice Research Database from 1992 to 2000, with a mean of 1.8 million
      registered patients. We identified new occurrences of GBS and estimated age- and
      sex-specific and age-standardized incidence rates. We then determined whether the
      date of diagnosis was made within 42 days of any immunization and estimated the
      relative risk of diagnosis following immunization after adjusting for age and
      sex. RESULTS: There were 228 incident cases of GBS, including 107 women and 121
      men. The age-standardized incidence rate per 100 000 person-years was 1.22 (95%
      confidence interval [CI], 0.98-1.46) in women and 1.45 (95% CI, 1.19-1.72) in
      men. Age-specific incidence rates per 100 000 person-years were highest in men
      aged 65 to 74 years (3.86; 95% CI, 2.50-5.70) and women aged 75 to 84 years
      (2.54; 95% CI, 1.39-4.27). There were 7 cases (3.1%) in which the onset occurred
      within 42 days of any immunization; 3 of the 7 cases occurred after influenza
      immunization. There were 221 cases (97.0%) that were not associated with
      immunization. The adjusted relative risk during the 42 days after immunization
      was 1.03 (95% CI, 0.48-2.18; P = .94). CONCLUSIONS: There is either minimal or no
      risk of GBS associated with routine immunization practice in the United Kingdom.
      Obtaining a precise estimate of any potential risk associated with an individual
      vaccine would require a study with more GBS cases.

PMID- 16801514
TI  - Effectiveness of foot orthoses to treat plantar fasciitis: a randomized trial.
AB  - BACKGROUND: Plantar fasciitis is one of the most common foot complaints. It is
      often treated with foot orthoses; however, studies of the effects of orthoses are
      generally of poor quality, and to our knowledge, no trials have investigated long
      term effectiveness. The aim of this trial was to evaluate the short- and long
      term effectiveness of foot orthoses in the treatment of plantar fasciitis.
      METHODS: A pragmatic, participant-blinded, randomized trial was conducted from
      April 1999 to July 2001. The duration of follow-up for each participant was 12
      months. One hundred and thirty-five participants with plantar fasciitis from the
      local community were recruited to a university-based clinic and were randomly
      allocated to receive a sham orthosis (soft, thin foam), a prefabricated orthosis
      (firm foam), or a customized orthosis (semirigid plastic). RESULTS: After 3
      months of treatment, estimates of effects on pain and function favored the
      prefabricated and customized orthoses over the sham orthoses, although only the
      effects on function were statistically significant. Compared with sham orthoses,
      the mean pain score (scale, 0-100) was 8.7 points better for the prefabricated
      orthoses (95% confidence interval, -0.1 to 17.6; P = .05) and 7.4 points better
      for the customized orthoses (95% confidence interval, -1.4 to 16.2; P = .10).
      Compared with sham orthoses, the mean function score (scale, 0-100) was 8.4
      points better for the prefabricated orthoses (95% confidence interval, 1.0-15.8;
      P = .03) and 7.5 points better for the customized orthoses (95% confidence
      interval, 0.3-14.7; P = .04). There were no significant effects on primary
      outcomes at the 12-month review. CONCLUSIONS: Foot orthoses produce small short
      term benefits in function and may also produce small reductions in pain for
      people with plantar fasciitis, but they do not have long-term beneficial effects
      compared with a sham device. The customized and prefabricated orthoses used in
      this trial have similar effectiveness in the treatment of plantar fasciitis.

PMID- 16801515
TI  - Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective
      study of 28 812 postmenopausal women.
AB  - BACKGROUND: Coffee intake may be associated with reduced risk of type 2 diabetes
      mellitus because of minerals, phytochemicals, and antioxidants in coffee, but the
      role of caffeine is unclear. Our objective was to examine the association between
      total, caffeinated, and decaffeinated coffee intake, as assessed by food
      frequency questionnaire at baseline, and risk of incident type 2 diabetes
      mellitus. METHODS: This prospective analysis of the Iowa Women's Health Study
      (1986-1997) included 28 812 postmenopausal women free of diabetes and
      cardiovascular disease in the general community. The main outcome measure was
      incident type 2 diabetes mellitus as determined by mailed questionnaire. RESULTS:
      Coffee intake was categorized as 0, less than 1, 1 to 3, 4 to 5, and 6 or more
      cups per day. During 11 years of follow-up, there were 1418 incident cases of
      diabetes. Relative risks (RRs) were adjusted for a variety of demographic,
      adiposity, and lifestyle measures. Compared with women who reported 0 cups of
      coffee per day, women who consumed 6 or more cups per day had a 22% lower risk
      (RR = 0.78; 95% confidence interval [CI], 0.61-1.01) of diabetes (P for linear
      trend across categories, .06). This association appeared to be largely explained
      by decaffeinated coffee (RR = 0.67; 95% CI, 0.42-1.08; P for trend, .006) rather
      than regular coffee (RR = 0.79; 95% CI, 0.59-1.05; P for trend, .90). Intake of
      magnesium and phytate did not explain these associations. Intakes of caffeine
      from all sources was not associated with risk of diabetes. CONCLUSION: Coffee
      intake, especially decaffeinated, was inversely associated with risk of type 2
      diabetes mellitus in this cohort of postmenopausal women.

PMID- 16801516
TI  - A community-wide pertussis outbreak: an argument for universal booster
      vaccination.
AB  - BACKGROUND: Pertussis incidence has increased in the United States since 1980,
      punctuated by outbreaks that involve adults and adolescents. We investigated a
      community-wide outbreak and studied risk factors among adults to identify
      prevention and control opportunities. METHODS: We analyzed surveillance data,
      interviewed patients, visited outbreak sites, and conducted a case-control study
      of risk factors for first-in-household adult infection during a Jackson County,
      Oregon, outbreak in 2003. RESULTS: In Jackson County, 135 pertussis cases were
      reported; the incidence was 71 per 100 000 population compared with 0 to 1 per
      100 000 population from 1995 through 2001. Case investigations identified 2658
      close contacts (19.7 per case); 1050 (40%) received antibiotic prophylaxis. Older
      children and adolescents (aged 10-17 years) and adults (aged > or =18 years)
      accounted for 67% of cases. Five infants were hospitalized (192 hospitalizations
      per 100 000 infants) compared with 18 in the remainder of the state (33 per 100
      000 infants). Many cases occurred among epidemiologically linked clusters of
      varied composition, such as jail inmates and employees, methamphetamine users,
      low-income housing residents, school students and employees, and employees in
      certain work settings. Adult patients were more likely than controls to live with
      children aged 6 to 10 years (odds ratio, 6.4; 95% confidence interval, 1.8-23.4)
      and less likely to report a complete childhood vaccination history (odds ratio,
      0.1; 95% confidence interval, 0.003-0.9). CONCLUSION: The predominance of
      adolescent and adult cases, appearance of new clusters despite aggressive control
      efforts, clustering of cases in hard-to-reach populations, and absence of
      modifiable risk factors for adult disease in this outbreak all suggest that
      universal booster vaccination of adolescents and adults might offer the only
      effective means to prevent such events in the future.

PMID- 16801517
TI  - Erectile dysfunction and thyroid disorders.

PMID- 16801518
TI  - Declining estrogen use in young women with Turner syndrome.

PMID- 16801519
TI  - Potential impact of sleep disorder treatment in fibromyalgia patients.

PMID- 16801520
TI  - The ethical requirement to provide hydration and nutrition.

PMID- 16801521
TI  - Mechanism of action of ranolazine.

PMID- 16801522
TI  - Good outcomes in coronary artery disease without invasive procedures.

PMID- 16801523
TI  - Diabetes, fitness, and body mass index.

PMID- 16801524
TI  - C-reactive protein and cardiovascular risk in the Framingham Study.

PMID- 16801525
TI  - Expression of prostasin and protease nexin-1 in rhesus monkey (Macaca mulatta)
      endometrium and placenta during early pregnancy.
AB  - Serine proteases have been documented to play key roles in uterine matrix
      turnover and trophoblastic invasion during implantation. Roles of prostasin
      serine protease in these processes, however, are currently unclear. The present
      study was first conducted to investigate the colocalization of prostasin and its
      cognate serpin, protease nexin-1 (PN-1), in rhesus monkey endometrium and
      placenta on days 12, 18, and 26 of pregnancy by using in situ hybridization (ISH)
      and immunohistochemistry. With ISH, expression of prostasin mRNA was intensely
      localized in the glandular epithelium on days 12 and 18 and in the placental
      villi, trophoblastic column, trophoblastic shell, and fetal-maternal border on
      days 18 and 26. With the progress of pregnancy, expression level in the glandular
      epithelium was significantly decreased, and the accumulation in the placental
      compartments was further increased. In addition, the stroma and arterioles
      exhibited modest levels of prostasin signals. However, expression level of PN-1
      in these compartments on adjacent sections in the three stages of early pregnancy
      was weak or below the level of detection. Prostasin protein expression in the
      endometrium was found to be consistent with the distribution patterns revealed in
      the ISH experiments. It may be suggested from these results that prostasin is
      involved in endometrial epithelial morphology establishment, tissue remodeling,
      and trophoblastic invasion during early pregnancy. The cognate serpin PN-1 was
      not coordinately expressed along with prostasin, creating a tissue environment
      favorable for proteolytic activities of prostasin during early pregnancy events.

PMID- 16801526
TI  - HuD distribution changes in response to heat shock but not neurotrophic
      stimulation.
AB  - Cellular stress leads to a change in distribution of RNA-binding proteins. HuR, a
      member of the ELAV/Hu family of RNA-binding proteins, is nuclear in distribution
      and following heat shock is found in large cytoplasmic stress granules where
      translation is inhibited. HuD, another ELAV/Hu RNA-binding protein, stabilizes
      the GAP-43 mRNA in response to nerve growth factor (NGF) stimulation in PC12
      cells. We were interested in determining the nuclear distribution of HuD and if
      neurotrophic stimulation induced changes in the distribution of HuD. In PC12
      cells, we found, as expected, that HuR translocates from the nucleus to the
      cytoplasm in response to heat shock. In response to heat shock, HuD forms large
      cytoplasmic stress granules, consistent with a role for HuD in the cessation of
      translation. In unstimulated cells, HuD is distributed in small granules in the
      cytoplasm and is consistently present at low levels in the nucleus. Stimulation
      of PC12 cells with NGF induces neuronal differentiation including outgrowth of
      neurites and increased levels of GAP-43 protein, whereas HuD remains localized in
      small cytoplasm granules and is still present in the nucleus. These results
      suggest that, following neurotrophic stimulation, the lack of changes in HuD
      distribution are due to continued steady state of HuD nuclear shuttling in PC12
      cells, or that HuD is not normally shuttled from the nucleus in response to NGF.

PMID- 16801527
TI  - Tubular stress proteins and nitric oxide synthase expression in rat kidney
      exposed to mercuric chloride and melatonin.
AB  - Stress proteins such as HSP70 members (HSP72 and GRP75) and metallothionein (MT)
      protect the kidney against oxidative damage and harmful metals, whereas inducible
      nitric oxide synthase (iNOS) regulates tubular functions. A single dose of
      mercuric chloride (HgCl(2)) can cause acute renal failure in rats, its main
      target being the proximal tubule. Oxidative damage has been proposed as one of
      its pathogenic mechanisms. In this study we tested whether melatonin (MEL), a
      powerful antioxidant compound, is effective against HgCl(2) nephrotoxicity. Rats
      were treated with saline, HgCl(2) (3.5 mg/kg), MEL (5 mg/kg), and MEL + HgCl(2)
      and examined after 24 hr for HSP72, GRP75, MT, and iNOS by immunohistochemistry
      and immunoblotting. Tubular effects of the treatment were then characterized by
      ultrastructure. In the HgCl(2) group, all markers were overexpressed in
      convoluted proximal tubules and sometimes in distal tubules. In the MEL + HgCl(2)
      group, GRP75 and iNOS decreased in convoluted and straight proximal tubules,
      whereas HSP72 and MT persisted more than the saline and MEL-only groups. Tubular
      damage and mitochondrial morphometry were improved by MEL pretreatment. In
      conclusion, the beneficial effect of MEL against HgCl(2) nephrotoxicity was
      outlined morphologically and by the reduction of the tubular expression of stress
      proteins and iNOS. These markers could represent sensitive recovery index against
      mercury damage.

PMID- 16801528
TI  - Epithelial trafficking of Sonic hedgehog by megalin.
AB  - We present here evidence of in vivo epithelial endocytosis and trafficking of non
      lipid-modified Sonic hedgehog (ShhN) when infused into rat efferent ducts via
      microinjection. Initially, exogenous ShhN is detected in endocytic vesicles and
      early endosomes located near the apical plasma membrane of non-ciliated cells.
      Within 30-60 min following infusion, ShhN can be detected in lysosomes and at
      basolateral regions of non-ciliated cells. Basolaterally, ShhN was observed along
      the extracellular surfaces of interdigitated plasma membranes of adjacent cells
      and in the extracellular compartment underlying the efferent duct epithelium.
      Uptake and subcellular trafficking of infused ShhN by non-ciliated cells could be
      blocked by either anti-megalin IgG or the megalin antagonist, RAP. Ciliated
      cells, which do not express megalin, displayed little if any apical
      internalization of ShhN even though they were found to express Patched-1.
      However, ShhN was found in coated pits of lateral plasma membranes of ciliated
      cells as well as in underlying endocytic vesicles. We conclude that megalin
      mediated endocytosis of ShhN can occur in megalin-expressing epithelia in vivo,
      and that the internalized ShhN can be targeted to the lysosome or transcytosed in
      the plane of the epithelium or across the epithelium. These findings highlight
      the multiple mechanisms by which megalin may influence Shh morphogen gradients in
      vivo.

PMID- 16801529
TI  - In situ localization of P-glycoprotein (ABCB1) in human and rat brain.
AB  - Transport of several xenobiotics including pharmacological agents into or out of
      the central nervous system (CNS) involves the expression of ATP-dependent,
      membrane-bound efflux transport proteins such as P-glycoprotein (P-gp) at the
      blood-brain barrier (BBB). Previous studies have documented gene and protein
      expression of P-gp in brain microvessel endothelial cells. However, the exact
      localization of P-gp, particularly at the abluminal side of the BBB, remains
      controversial. In the present study we examined the cellular/subcellular
      distribution of P-gp in situ in rat and human brain tissues using immunogold
      cytochemistry at the electron microscope level. P-gp localizes to both the
      luminal and abluminal membranes of capillary endothelial cells as well as to
      adjacent pericytes and astrocytes. Subcellularly, P-gp is distributed along the
      nuclear envelope, in caveolae, cytoplasmic vesicles, Golgi complex, and rough
      endoplasmic reticulum (RER). These results provide evidence for the expression of
      P-gp in human and rodent brain capillary along their plasma membranes as well as
      at sites of protein synthesis, glycosylation, and membrane trafficking. In
      addition, its presence at the luminal and abluminal poles of the BBB, including
      pericytes and astrocyte plasma membranes, suggests that this glycoprotein may
      regulate drug transport processes in the entire CNS BBB at both the cellular and
      subcellular level.

PMID- 16801530
TI  - Profile of Susan Band Horwitz.

PMID- 16801531
TI  - Monocyte accumulation in mouse atherogenesis is progressive and proportional to
      extent of disease.
AB  - Monocytes participate importantly in the pathogenesis of atherosclerosis, but
      their spatial and temporal recruitment from circulation remains uncertain. This
      study tests the hypothesis that monocyte accumulation in atheroma correlates with
      the extent of disease by using a sensitive and simple quantitative assay that
      allows tracking of highly enriched populations of blood monocytes. A two-step
      isolation method yielded viable and functionally intact highly enriched
      peripheral blood monocyte populations (>90%). Recipient mice received syngeneic
      monocytes labeled in two ways: by transgenically expressing EGFP or with a
      radioactive tracer [(111)In]oxine. After 5 days, more labeled cells accumulated
      in the aorta, principally the aortic root and ascending aorta, of 10-wk-old ApoE(
      /-) compared with 10-wk-old C57BL/6 mice (223 +/- 3 vs. 87 +/- 22 cells per
      aorta). Considerably more monocytes accumulated in 20-wk-old ApoE(-/-) mice on
      either chow (314 +/- 41 cells) or high-cholesterol diet (395 +/- 53 cells). Fifty
      week-old ApoE(-/-) mice accumulated even more monocytes in the aortic root,
      ascending aorta, and thoracic aorta after both chow (503 +/- 67 cells) or high
      cholesterol diet (648 +/- 81 cells). Labeled monocyte content in the aorta
      consistently correlated with lesion surface area. These data indicate that
      monocytes accumulate continuously during atheroma formation, accumulation
      increases in proportion to lesion size, and recruitment is augmented with
      hypercholesterolemia. These results provide insights into mechanisms of
      atherogenesis and have implications for the duration of therapies directed at
      leukocyte recruitment.

PMID- 16801532
TI  - CD28-stimulated ERK2 phosphorylation is required for polarization of the
      microtubule organizing center and granules in YTS NK cells.
AB  - Activation of natural killer (NK) cell cytotoxicity requires adhesion and
      formation of a conjugate with a susceptible target cell, followed by actin
      polymerization, and polarization of the microtubule organizing center (MTOC) and
      cytolytic granules to the NK cell immune synapse. Here, by using the YTS NK cell
      line as a model, CD28 is shown to be an activating receptor. It signals
      cytotoxicity in a process dependent on phosphoinositide-3 kinase activation,
      leading to sustained extracellular signal-regulated kinase 2 (ERK2)
      phosphorylation. ERK and phospho-ERK localize to microtubule filaments. Neither
      conjugation with targets nor actin polymerization is affected by blocking ERK2
      activation. However, both polarization of the MTOC and cytolytic granules to the
      synaptic region and NK cell cytotoxicity are strongly reduced by blocking ERK2
      activation. A role for the CD28/CD80 interaction in cytotoxicity of human
      peripheral NK cells also was established. By contrast, lymphocyte function
      associated antigen 1 (LFA-1) ligation transduces only a transient ERK2 activation
      and fails to induce killing in YTS cells. Thus, in YTS cells, a CD28 signal is
      used to polarize the MTOC and cytolytic granules to the NK cell immune synapse by
      stimulating sustained ERK2 activation.

PMID- 16801534
TI  - STAT3: a multifaceted oncogene.

PMID- 16801533
TI  - Death-receptor activation halts clathrin-dependent endocytosis.
AB  - Endocytosis is crucial for various aspects of cell homeostasis. Here, we show
      that proapoptotic death receptors (DRs) trigger selective destruction of the
      clathrin-dependent endocytosis machinery. DR stimulation induced rapid, caspase
      mediated cleavage of key clathrin-pathway components, halting cellular uptake of
      the classic cargo protein transferrin. DR-proximal initiator caspases cleaved the
      clathrin adaptor subunit AP2alpha between functionally distinct domains, whereas
      effector caspases processed clathrin's heavy chain. DR5 underwent ligand-induced,
      clathrin-mediated endocytosis, suggesting that internalization of DR signaling
      complexes facilitates clathrin-pathway targeting by caspases. An endocytosis
      blocking, temperature-sensitive dynamin-1 mutant attenuated DR internalization,
      enhanced caspase stimulation downstream of DRs, and increased apoptosis. Thus, DR
      triggered caspase activity disrupts clathrin-dependent endocytosis, leading to
      amplification of programmed cell death.

PMID- 16801535
TI  - Holocene elephant seal distribution implies warmer-than-present climate in the
      Ross Sea.
AB  - We show that southern elephant seal (Mirounga leonina) colonies existed proximate
      to the Ross Ice Shelf during the Holocene, well south of their core sub-Antarctic
      breeding and molting grounds. We propose that this was due to warming (including
      a previously unrecognized period from approximately 1,100 to 2,300 (14)C yr B.P.)
      that decreased coastal sea ice and allowed penetration of warmer-than-present
      climate conditions into the Ross Embayment. If, as proposed in the literature,
      the ice shelf survived this period, it would have been exposed to environments
      substantially warmer than present.

PMID- 16801536
TI  - Chromophore regeneration: melanopsin does its own thing.

PMID- 16801537
TI  - Thermal fluctuations of grafted microtubules provide evidence of a length
      dependent persistence length.
AB  - Microtubules are hollow cylindrical structures that constitute one of the three
      major classes of cytoskeletal filaments. On the mesoscopic length scale of a
      cell, their material properties are characterized by a single stiffness
      parameter, the persistence length l(p). Its value, in general, depends on the
      microscopic interactions between the constituent tubulin dimers and the
      architecture of the microtubule. Here, we use single-particle tracking methods
      combined with a fluctuation analysis to systematically study the dependence of
      l(p) on the total filament length L. Microtubules are grafted to a substrate with
      one end free to fluctuate in three dimensions. A fluorescent bead is attached
      proximally to the free tip and is used to record the thermal fluctuations of the
      microtubule's end. The position distribution functions obtained with this assay
      allow the precise measurement of l(p) for microtubules of different contour
      length L. Upon varying L between 2.6 and 47.5 mum, we find a systematic increase
      of l(p) from 110 to 5,035 mum. At the same time we verify that, for a given
      filament length, the persistence length is constant over the filament within the
      experimental accuracy. We interpret this length dependence as a consequence of a
      nonnegligible shear deflection determined by subnanometer relative displacement
      of adjacent protofilaments. Our results may shine new light on the function of
      microtubules as sophisticated nanometer-sized molecular machines and give a
      unified explanation of seemingly uncorrelated spreading of microtubules'
      stiffness previously reported in literature.

PMID- 16801538
TI  - TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and
      induction of changes in cellular morphology.
AB  - Small GTPases of the Rho family play key roles in the formation of neuronal axons
      and dendrites by transducing signals from guidance cues, such as neurotrophins,
      to the actin cytoskeleton. However, there is little insight into the mechanism by
      which neurotrophins regulate Rho GTPases. Here, we show the crucial role of the
      ubiquitous Rac1-specific guanine nucleotide exchange factor, Tiam1 (T lymphoma
      invasion and metastasis 1), in transducing a neurotrophin-mediated change in cell
      shape. We demonstrate that BDNF, acting through TrkB, directly binds and
      specifically activates Tiam1 by phosphorylating Tyr-829, leading to Rac1
      activation and lamellipodia formation in Cos-7 cells and increased neurite
      outgrowth from cortical neurons. A point mutation in Tiam1, Tyr-829 to Phe-829,
      blocked these BDNF-induced changes in cellular morphology. The findings are
      evidence of a previously uncharacterized mechanism for the activation of Tiam1
      and of a role for this effector in neurotrophin-mediated signal transduction
      leading to changes in cellular morphology.

PMID- 16801539
TI  - Effective gene therapy in an authentic model of Tay-Sachs-related diseases.
AB  - Tay-Sachs disease is a prototypic neurodegenerative disease. Lysosomal storage of
      GM2 ganglioside in Tay-Sachs and the related disorder, Sandhoff disease, is
      caused by deficiency of beta-hexosaminidase A, a heterodimeric protein. Tay-Sachs
      related diseases (GM2 gangliosidoses) are incurable, but gene therapy has the
      potential for widespread correction of the underlying lysosomal defect by means
      of the secretion-recapture cellular pathway for enzymatic complementation.
      Sandhoff mice, lacking the beta-subunit of hexosaminidase, manifest many signs of
      classical human Tay-Sachs disease and, with an acute course, die before 20 weeks
      of age. We treated Sandhoff mice by stereotaxic intracranial inoculation of
      recombinant adeno-associated viral vectors encoding the complementing human beta
      hexosaminidase alpha and beta subunit genes and elements, including an HIV tat
      sequence, to enhance protein expression and distribution. Animals survived for >1
      year with sustained, widespread, and abundant enzyme delivery in the nervous
      system. Onset of the disease was delayed with preservation of motor function;
      inflammation and GM2 ganglioside storage in the brain and spinal cord was
      reduced. Gene delivery of beta-hexosaminidase A by using adeno-associated viral
      vectors has realistic potential for treating the human Tay-Sachs-related
      diseases.

PMID- 16801540
TI  - Insights into the mechanism of microtubule stabilization by Taxol.
AB  - The antitumor drug Taxol stabilizes microtubules and reduces their dynamicity,
      promoting mitotic arrest and cell death. Upon assembly of the alpha/beta-tubulin
      heterodimer, GTP bound to beta-tubulin is hydrolyzed to GDP reaching a steady
      state equilibrium between free tubulin dimers and microtubules. The binding of
      Taxol to beta-tubulin in the polymer results in cold-stable microtubules at the
      expense of tubulin dimers, even in the absence of exogenous GTP. However, there
      is little biochemical insight into the mechanism(s) by which Taxol stabilizes
      microtubules. Here, we analyze the structural changes occurring in both beta- and
      alpha-tubulin upon microtubule stabilization by Taxol. Hydrogen/deuterium
      exchange (HDX) coupled to liquid chromatography-electrospray ionization MS
      demonstrated a marked reduction in deuterium incorporation in both beta-and alpha
      tubulin when Taxol was present. Decreased local HDX in peptic peptides was mapped
      on the tubulin structure and revealed both expected and new dimer-dimer
      interactions. The increased rigidity in Taxol microtubules was distinct from and
      complementary to that due to GTP-induced polymerization. The Taxol-induced
      changes in tubulin conformation act against microtubule depolymerization in a
      precise directional way. These results demonstrate that HDX coupled to liquid
      chromatography-electrospray ionization MS can be effectively used to study
      conformational effects induced by small ligands on microtubules. The present
      study also opens avenues for locating drug and protein binding sites and for
      deciphering the mechanisms by which their interactions alter the conformation of
      microtubules and tubulin dimers.

PMID- 16801541
TI  - Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression
      independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6.
AB  - Recently, it has been suggested that hepcidin, a peptide involved in iron
      homeostasis, is regulated by bone morphogenetic proteins (BMPs), apparently by
      binding to hemojuvelin (Hjv) as a coreceptor and signaling through Smad4. We
      investigate the role of Hfe, Tfr2 (transferrin receptor 2), and IL-6 in BMP2-,
      BMP4-, and BMP9-stimulated up-regulation of murine hepcidin, because these
      molecules, like Hjv, are known to be involved in hepcidin signaling. We show that
      the BMP signaling pathway acts independently of Hfe, Tfr2, and IL-6: The response
      to BMP2, BMP4, and BMP9 is similar in isolated hepatocytes of wild-type, Hfe(-/
      ), IL-6(-/-), and Tfr2(m) mutant mice. The potency of different human BMPs in
      stimulating hepcidin transcription by murine primary hepatocytes is BMP9 > BMP4 >
      BMP2. However, in human HepG2 cells, BMP4 and BMP9 are equally potent, whereas
      BMP2 requires a higher dose to become an effective hepcidin activator. Moreover,
      all of the tested BMPs are more potent regulators of hepcidin than IL-6 and thus
      are the most potent known stimulators of hepcidin transcription.

PMID- 16801542
TI  - Therapy of ovarian cancers with targeted cytotoxic analogs of bombesin,
      somatostatin, and luteinizing hormone-releasing hormone and their combinations.
AB  - The aim of this study was to investigate the effect of treatment of experimental
      ovarian cancers with targeted cytotoxic analogs as single compounds and in
      combination. Targeted cytotoxic analogs of bombesin (AN-215), somatostatin (AN
      238), and luteinizing hormone-releasing hormone (AN-207) consisted of 2
      pyrrolinodoxorubicin (AN-201) linked to the respective peptide carrier. AN-238 at
      200 nmol/kg significantly inhibited growth of UCI-107, ES-2 and OV-1063 ovarian
      cancers. AN-215 alone at 200 nmol/kg and its combination with AN-238 at one-half
      of the dose were also able to inhibit the growth of UCI-107 tumors. A combination
      of AN-238 with AN-207at 50% of the dose strongly suppressed the proliferation of
      ES-2 and OV-1063 ovarian tumors. Cytotoxic radical AN-201 was toxic and had no
      significant effect on tumor growth. In contrast, the toxicity of the conjugated
      peptide analogs was low. Because ovarian cancers tend to acquire chemoresistance,
      we used real-time PCR to measure the mRNA expression of multidrug resistance
      protein 1, multidrug resistance-related protein 1, and breast cancer resistance
      protein after treatment. Low or no induction of multidrug resistance protein 1,
      multidrug resistance-related protein, and breast cancer resistance protein
      occurred after treatment with AN-238, AN-215, and the combination of AN-238 with
      AN-207 or AN-215. These results demonstrate that a therapy with cytotoxic analogs
      such as single agents and combinations is effective and nontoxic. Our work
      suggests that cytotoxic peptide analogs of luteinizing hormone-releasing hormone,
      somatostatin, and bombesin could be used for the therapy of ovarian cancers,
      considering the lack of induction of chemoresistance.

PMID- 16801543
TI  - Controlling interlayer diffusion to achieve sustained, multiagent delivery from
      layer-by-layer thin films.
AB  - We present the fabrication of conformal, hydrolytically degradable thin films
      capable of administering sustained, multiagent release profiles. Films are
      constructed one molecular layer at a time by using the layer-by-layer, directed
      deposition technique; the subsequent hydrolytic surface erosion of these systems
      results in the release of incorporated materials in a sequence that reflects
      their relative positions in the film. The position of each species is determined
      by its ability to diffuse throughout the film architecture, and, as such, the
      major focus of this work is to define strategies that physically block interlayer
      diffusion during assembly to create multicomponent, stratified films. By using a
      series of radiolabeled polyelectrolytes as experimental probes, we show that
      covalently crosslinked barriers can effectively block interlayer diffusion,
      leading to compartmentalized structures, although even very large numbers of
      ionically crosslinked (degradable or nondegradable) barrier layers cannot block
      interlayer diffusion. By using these principles, we designed degradable films
      capable of extended release as well as both parallel and serial multiagent
      release. The ability to fabricate multicomponent thin films with nanoscale
      resolution may lead to a host of new materials and applications.

PMID- 16801544
TI  - Physical training and metabolic supplementation reduce spontaneous
      atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice.
AB  - Moderate physical exercise (PE) combined with metabolic treatment (MT)
      (antioxidants and l-arginine) are well known to reduce atherosclerotic lesion
      formation in hypercholesterolemic mice. However, the long-term beneficial effects
      on unstable atheroma remain poorly understood. We started early PE training in
      large groups of 6-week-old hypercholesterolemic mice (by graduated swimming)
      alone or in combination with nutritional supplementation (1.0% vitamin E added to
      the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water).
      Inactive controls did not receive PE. The spontaneous development of
      atherosclerotic plaque rupture (associated with advanced atherosclerosis) and
      survival rates were evaluated. Moderate PE elicited an increase in plasma levels
      of nitric oxide. Early combined treatment with PE and MT in the
      hypercholesterolemic mice significantly reduced lesions (also detected
      noninvasively at 10 months) and spontaneous atherosclerotic plaque rupture and
      prolonged survival more effectively than each intervention alone. Thus, early
      concerted actions of MT and PE improve the natural history of atherosclerotic
      lesions and reduce the plaque instability in hypercholesterolemic mice.

PMID- 16801545
TI  - Snail family genes are required for left-right asymmetry determination, but not
      neural crest formation, in mice.
AB  - Snail family genes encode zinc finger transcriptional repressors that are key
      regulators of epithelial-mesenchymal transitions in vertebrates, including the
      transitions that generate the mesoderm and neural crest. Here, we show that,
      contrary to observations in frog and avian embryos, the Snail family genes Snail
      (Snai1) and Slug (Snai2) are not required for formation and delamination of the
      neural crest in mice. However, embryos with conditional inactivation of Snai1
      function exhibit defects in left-right asymmetry determination. This work
      demonstrates that although some aspects of Snail family gene function, such as a
      role in left-right asymmetry determination, appear to be evolutionarily
      conserved, their role in neural crest cell formation and delamination is not.

PMID- 16801546
TI  - Island radiation on a continental scale: exceptional rates of plant
      diversification after uplift of the Andes.
AB  - Species radiations provide unique insights into evolutionary processes underlying
      species diversification and patterns of biodiversity. To compare plant
      diversification over a similar time period to the recent cichlid fish radiations,
      which are an order of magnitude faster than documented bird, arthropod, and plant
      radiations, we focus on the high-altitude flora of the Andes, which is the most
      species-rich of any tropical mountains. Because of the recent uplift of the
      northern Andes, the upland environments where much of this rich endemic flora is
      found have been available for colonization only since the late Pliocene or
      Pleistocene, 2-4 million years (Myr) ago. Using DNA sequence data we identify a
      monophyletic group within the genus Lupinus representing 81 species endemic to
      the Andes. The age of this clade is estimated to be 1.18-1.76 Myr, implying a
      diversification rate of 2.49-3.72 species per Myr. This exceeds previous
      estimates for plants, providing the most spectacular example of explosive plant
      species diversification documented to date. Furthermore, it suggests that the
      high cichlid diversification rates are not unique. Lack of key innovations
      associated with the Andean Lupinus clade suggests that diversification was driven
      by ecological opportunities afforded by the emergence of island-like habitats
      after Andean uplift. Data from other genera indicate that lupines are one of a
      set of similarly rapid Andean plant radiations, continental in scale and island
      like in stimulus, suggesting that the high-elevation Andean flora provides a
      system that rivals other groups, including cichlids, for understanding rapid
      species diversification.

PMID- 16801548
TI  - Discovery of aminoacyl-tRNA synthetase activity through cell-surface display of
      noncanonical amino acids.
AB  - The incorporation of noncanonical amino acids into recombinant proteins in
      Escherichia coli can be facilitated by the introduction of new aminoacyl-tRNA
      synthetase activity into the expression host. We describe here a screening
      procedure for the identification of new aminoacyl-tRNA synthetase activity based
      on the cell surface display of noncanonical amino acids. Screening of a
      saturation mutagenesis library of the E. coli methionyl-tRNA synthetase (MetRS)
      led to the discovery of three MetRS mutants capable of incorporating the long
      chain amino acid azidonorleucine into recombinant proteins with modest
      efficiency. The Leu-13 --> Gly (L13G) mutation is found in each of the three
      MetRS mutants, and the MetRS variant containing this single mutation is highly
      efficient in producing recombinant proteins that contain azidonorleucine.

PMID- 16801547
TI  - A high-throughput gene knockout procedure for Neurospora reveals functions for
      multiple transcription factors.
AB  - The low rate of homologous recombination exhibited by wild-type strains of
      filamentous fungi has hindered development of high-throughput gene knockout
      procedures for this group of organisms. In this study, we describe a method for
      rapidly creating knockout mutants in which we make use of yeast recombinational
      cloning, Neurospora mutant strains deficient in nonhomologous end-joining DNA
      repair, custom-written software tools, and robotics. To illustrate our approach,
      we have created strains bearing deletions of 103 Neurospora genes encoding
      transcription factors. Characterization of strains during growth and both asexual
      and sexual development revealed phenotypes for 43% of the deletion mutants, with
      more than half of these strains possessing multiple defects. Overall, the
      methodology, which achieves high-throughput gene disruption at an efficiency >90%
      in this filamentous fungus, promises to be applicable to other eukaryotic
      organisms that have a low frequency of homologous recombination.

PMID- 16801549
TI  - The solid-state architecture of a metallosupramolecular polyelectrolyte.
AB  - Self-assembly of Fe(II) and the ditopic ligand 1,4-bis(2,2':6',2''-terpyridine-4'
      yl)benzene results in equilibrium structures in solutions, so-called
      metallosupramolecular coordination polyelectrolytes (MEPEs). It is exceedingly
      difficult to characterize such macromolecular assemblies, because of the dynamic
      nature. Therefore, hardly any structural information is available for this type
      of material. Here, we show that from dilute solutions, where small aggregates
      predominate, it is possible to grow nanoscopic crystals at an interface. A near
      atomic resolution structure of MEPE is obtained by investigating the nanoscopic
      crystals with electron diffraction in combination with molecular modeling. The
      analysis reveals a primitive monoclinic unit cell (P2(1)/c space group, a = 10.4
      A, b = 10.7 A, c = 34.0 A, alpha = gamma = 90 degrees , beta = 95 degrees , rho =
      1.26 g/cm(3), and Z = 4). The MEPE forms linear rods, which are organized into
      sheets. Four sheets intersect the unit cell, while adjacent sheets are rotated by
      90 degrees with respect to each other. The pseudooctahedral coordination geometry
      of the Fe(II) centers is confirmed by Mossbauer spectroscopy. The combination of
      diffraction and molecular modeling presented here may be of general utility to
      address problems in structural materials science.

PMID- 16801550
TI  - Distinct structural and mechanical properties of the nuclear lamina in Hutchinson
      Gilford progeria syndrome.
AB  - The nuclear lamina is a network of structural filaments, the A and B type lamins,
      located at the nuclear envelope and throughout the nucleus. Lamin filaments
      provide the nucleus with mechanical stability and support many basic activities,
      including gene regulation. Mutations in LMNA, the gene encoding A type lamins,
      cause numerous human diseases, including the segmental premature aging disease
      Hutchinson-Gilford progeria syndrome (HGPS). Here we show that structural and
      mechanical properties of the lamina are altered in HGPS cells. We demonstrate by
      live-cell imaging and biochemical analysis that lamins A and C become trapped at
      the nuclear periphery in HGPS patient cells. Using micropipette aspiration, we
      show that the lamina in HGPS cells has a significantly reduced ability to
      rearrange under mechanical stress. Based on polarization microscopy results, we
      suggest that the lamins are disordered in the healthy nuclei, whereas the lamins
      in HGPS nuclei form orientationally ordered microdomains. The reduced
      deformability of the HGPS nuclear lamina possibly could be due to the inability
      of these orientationally ordered microdomains to dissipate mechanical stress.
      Surprisingly, intact HGPS cells exhibited a degree of resistance to acute
      mechanical stress similar to that of cells from healthy individuals. Thus, in
      contrast to the nuclear fragility seen in lmna null cells, the lamina network in
      HGPS cells has unique mechanical properties that might contribute to disease
      phenotypes by affecting responses to mechanical force and misregulation of
      mechanosensitive gene expression.

PMID- 16801551
TI  - Endocytic vesicle scission by lipid phase boundary forces.
AB  - Endocytosis in budding yeast is thought to occur in several phases. First, the
      membrane invaginates and then elongates into a tube. A vesicle forms at the end
      of the tube, eventually pinching off to form a "free" vesicle. Experiments show
      that actin polymerization is an active participant in the endocytic process,
      along with a number of membrane-associated proteins. Here we investigate the
      possible roles of these components in driving vesiculation by constructing a
      quantitative model of the process beginning at the stage where the membrane
      invagination has elongated into a tube encased in a sheath of membrane-associated
      protein. This protein sheath brings about the scission step where the vesicle
      separates from the tube. When the protein sheath is dynamin, it is commonly
      assumed that scission is brought about by the constriction of the sheath. Here,
      we show that an alternative scenario can work as well: The protein sheath acts as
      a "filter" to effect a phase separation of lipid species. The resulting line
      tension tends to minimize the interface between the tube region and the vesicle
      region. Interestingly, large vesicle size can further facilitate the reduction of
      the interfacial diameter down to a few nanometers, small enough so that thermal
      fluctuations can fuse the membrane and pinch off the vesicle. To deform the
      membrane into the tubular vesicle shape, the membrane elastic resistance forces
      must be balanced by some additional forces that we show can be generated by actin
      polymerization and/or myosin I. These active forces are shown to be important in
      successful scission processes as well.

PMID- 16801552
TI  - Base pair motions control the rates and distance dependencies of reductive and
      oxidative DNA charge transfer.
AB  - In 1999, Wan et al. [Proc. Natl. Acad. Sci. USA 96, 6014-6019] published a
      pioneering paper that established the entanglement between DNA base pair motions
      and the transfer time of the charge carrier. The DNA assemblies contained an
      ethidium covalently bound via a flexible alkyl chain to the 5' hydroxyl group of
      the DNA backbone. Although covalently attached, the loose way in which the
      ethidium was linked to DNA allowed for large degrees of conformational freedom
      and thus raised some concern with respect to conformational inhomogeneity. In
      this letter, we report studies on a different set of ethidium DNA conjugates. In
      contrast to the "Caltech systems," these conjugates contain ethidium tightly
      incorporated (as a base pair surrogate) into the DNA base stack, opposite to an
      abasic site analog. Despite the tight binding, we found that charge transfer from
      the photoexcited ethidium base pair surrogate across two or more base pairs is
      several orders of magnitude slower than in case of the DNA systems bearing the
      tethered ethidium. To further broaden the scope of this account, we compared
      (oxidative) electron hole transfer and (reductive) electron transfer using the
      same ethidium chromophore as a charge donor in combination with two different
      charge acceptors. We found that both electron and hole transfer are characterized
      by similar rates and distance dependencies. The results demonstrate the
      importance of nuclear motions and conformational flexibility and underline the
      presence of a base gating mechanism, which appears to be generic to electronic
      transfer processes through pi-stacked nucleic acids.

PMID- 16801553
TI  - Economic, neurobiological, and behavioral perspectives on building America's
      future workforce.
AB  - A growing proportion of the U.S. workforce will have been raised in disadvantaged
      environments that are associated with relatively high proportions of individuals
      with diminished cognitive and social skills. A cross-disciplinary examination of
      research in economics, developmental psychology, and neurobiology reveals a
      striking convergence on a set of common principles that account for the potent
      effects of early environment on the capacity for human skill development. Central
      to these principles are the findings that early experiences have a uniquely
      powerful influence on the development of cognitive and social skills and on brain
      architecture and neurochemistry, that both skill development and brain maturation
      are hierarchical processes in which higher level functions depend on, and build
      on, lower level functions, and that the capacity for change in the foundations of
      human skill development and neural circuitry is highest earlier in life and
      decreases over time. These findings lead to the conclusion that the most
      efficient strategy for strengthening the future workforce, both economically and
      neurobiologically, and improving its quality of life is to invest in the
      environments of disadvantaged children during the early childhood years.

PMID- 16801554
TI  - Butyrophilin controls milk fat globule secretion.
AB  - The molecular mechanism underlying milk fat globule secretion in mammary
      epithelial cells ostensibly involves the formation of complexes between plasma
      membrane butyrophilin and cytosolic xanthine oxidoreductase. These complexes bind
      adipophilin in the phospholipid monolayer of milk secretory granules, the
      precursors of milk fat globules, enveloping the nascent fat globules in a layer
      of plasma membrane and pinching them off the cell. However, using freeze-fracture
      immunocytochemistry, we find these proteins in locations other than those
      previously inferred. Significantly, butyrophilin in the residual plasma membrane
      of the fat globule envelope is concentrated in a network of ridges that are
      tightly apposed to the monolayer derived from the secretory granule, and the
      ridges coincide with butyrophilin labeling in the globule monolayer. Therefore,
      we propose that milk fat globule secretion is controlled by interactions between
      plasma membrane butyrophilin and butyrophilin in the secretory granule
      phospholipid monolayer rather than binding of butyrophilin-xanthine
      oxidoreductase complexes to secretory granule adipophilin.

PMID- 16801555
TI  - Breakup of a homeobox cluster after genome duplication in teleosts.
AB  - Several families of homeobox genes are arranged in genomic clusters in metazoan
      genomes, including the Hox, ParaHox, NK, Rhox, and Iroquois gene clusters. The
      selective pressures responsible for maintenance of these gene clusters are poorly
      understood. The ParaHox gene cluster is evolutionarily conserved between
      amphioxus and human but is fragmented in teleost fishes. We show that two basal
      ray-finned fish, Polypterus and Amia, each possess an intact ParaHox cluster;
      this implies that the selective pressure maintaining clustering was lost after
      whole-genome duplication in teleosts. Cluster breakup is because of gene loss,
      not transposition or inversion, and the total number of ParaHox genes is the same
      in teleosts, human, mouse, and frog. We propose that this homeobox gene cluster
      is held together in chordates by the existence of interdigitated control regions
      that could be separated after locus duplication in the teleost fish.

PMID- 16801556
TI  - On the origin and robustness of power-law species-area relationships in ecology.
AB  - We present an explanation for the widely reported power-law species-area
      relationship (SAR), which relates the area occupied by a biome to the number of
      species that it supports. We argue that power-law SARs are a robust consequence
      of a skewed species abundance distribution resembling a lognormal with higher
      rarity, together with the observation that individuals of a given species tend to
      cluster. We show that the precise form of the SAR transcends the specific details
      of organism interactions, enabling us to characterize its broad trends across
      taxa.

PMID- 16801557
TI  - Just one cross appears capable of dramatically altering the population biology of
      a eukaryotic pathogen like Toxoplasma gondii.
AB  - Toxoplasma gondii, an obligate intracellular protozoan of the phylum Apicomplexa,
      is estimated to infect over a billion people worldwide as well as a great many
      other mammalian and avian hosts. Despite this ubiquity, the vast majority of
      human infections in Europe and North America are thought to be due to only three
      genotypes. Using a genome-wide analysis of single-nucleotide polymorphisms, we
      have constructed a genealogy for these three lines. The data indicate that types
      I and III are second- and first-generation offspring, respectively, of a cross
      between a type II strain and one of two ancestral strains. An extant T. gondii
      strain (P89) appears to be the modern descendant of the non-type II parent of
      type III, making the full genealogy of the type III clonotype known. The
      simplicity of this family tree demonstrates that even a single cross can lead to
      the emergence and dominance of a new clonal genotype that completely alters the
      population biology of a sexual pathogen.

PMID- 16801558
TI  - Multiple routes lead to the native state in the energy landscape of the beta
      trefoil family.
AB  - In general, the energy landscapes of real proteins are sufficiently well designed
      that the depths of local energetic minima are small compared with the global bias
      of the native state. Because of the funneled nature of energy landscapes, models
      that lack energetic frustration have been able to capture the main structural
      features of the transition states and intermediates found in experimental studies
      of both small and large proteins. In this study we ask: Are the experimental
      differences in folding mechanisms among members of a particular structural family
      due to local topological constraints that deviate from the tertiary fold common
      to the family? The beta-trefoil structural family members IL-1beta,
      hisactophilin, and acidic/basic FGFs were chosen to address this question. It has
      been observed that the topological landscape of the beta-trefoils allows for the
      population of diverse, geometrically disconnected routes that provide
      energetically similar but structurally distinct ways for this family to fold.
      Small changes in topology or energetics can alter the preferred route. Taken
      together, these results indicate that the global fold of the beta-trefoil family
      determines the energy landscape but that the routes accessed on that landscape
      might differ as a result of functional requirements of the individual family
      members.

PMID- 16801559
TI  - CD4+ T cells and CXC chemokines modulate the pathogenesis of Staphylococcus
      aureus wound infections.
AB  - T cells are critical for the formation of intraabdominal abscesses by
      Staphylococcus aureus. We hypothesized that T cells modulate the development of
      experimental staphylococcal infections by controlling polymorphonuclear leukocyte
      (PMN) trafficking. In models of staphylococcal s.c. abscess formation, hindpaw
      infection, and surgical wound infection, S. aureus multiplied in the tissues of
      WT C57BL/6J mice and elicited a marked inflammatory response. CD4(+) alphabeta T
      cells homed to the surgical wound infection site of WT animals. In contrast,
      significantly fewer S. aureus were recovered from the tissues of mice deficient
      in alphabeta T cells, and the inflammatory response was considerably diminished
      compared with that of WT animals. Alphabeta T cell receptor (-/-) mice had
      significantly lower concentrations of PMN-specific CXC chemokines in wound tissue
      than did WT mice. The severity of the wound infection was enhanced by
      administration of a CXC chemokine and abrogated by antibodies that blocked the
      CXC receptor. An acapsular mutant was less virulent than the parental S. aureus
      strain in both the s.c. abscess and the surgical wound infection models in WT
      mice. These data reveal an important and underappreciated role for CD4(+)
      alphabeta T cells in S. aureus infections in controlling local CXC chemokine
      production, neutrophil recruitment to the site of infection, and subsequent
      bacterial replication.

PMID- 16801561
TI  - Turbulent flow properties of large-scale vortex systems.
AB  - Large-scale computations of dynamically interacting vortex tubes forming
      filaments are performed with a view toward investigating their relationship to
      turbulent fluid flow. It is shown that the statistical properties of the tubes
      are consistent with commonly accepted observations about turbulence such as the
      Kolmogorov inertial range spectrum and lognormality of the vorticity
      distribution. A loop-removal algorithm is demonstrated to reduce the nominally
      exponential growth rate in the number of tubes to linear growth without apparent
      harm to the underlying physics. In this form, a vortex tube method may become a
      practical means for simulating high Reynolds number turbulent flows.

PMID- 16801560
TI  - Nanog binds to Smad1 and blocks bone morphogenetic protein-induced
      differentiation of embryonic stem cells.
AB  - ES cells represent a valuable model for investigating early embryo development
      and hold promise for future regenerative medicine strategies. The self-renewal of
      pluripotent mouse ES cells has been shown to require extrinsic stimulation by the
      bone morphogenetic protein (BMP) and leukemia inhibitory factor signaling
      pathways and the expression of the transcription factors Oct4 and Nanog. However,
      the network of interactions among extrinsic and intrinsic determinants of ES cell
      pluripotency is currently poorly understood. Here, we show that Nanog expression
      is up-regulated in mouse ES cells by the binding of T (Brachyury) and STAT3 to an
      enhancer element in the mouse Nanog gene. We further show that Nanog blocks BMP
      induced mesoderm differentiation of ES cells by physically interacting with Smad1
      and interfering with the recruitment of coactivators to the active Smad
      transcriptional complexes. Taken together, our findings illustrate the existence
      of ES cell-specific regulatory networks that underlie the maintenance of ES cell
      pluripotency and provide mechanistic insights into the role of Nanog in this
      process.

PMID- 16801562
TI  - Identification of novel antimicrobials using a live-animal infection model.
AB  - The alarming increase of antibiotic-resistant bacterial pathogens points to the
      need for novel therapeutic approaches to combat infection. To discover novel
      antimicrobials, we devised a screen to identify compounds that promoted the
      survival of the model laboratory nematode Caenorhabditis elegans infected with
      the human opportunistic pathogen Enterococcus faecalis. E. faecalis colonizes the
      nematode intestinal tract, forming a persistent lethal infection. Infected
      nematodes were rescued by antibiotic treatment in a dose-dependent manner, and
      antibiotic treatment markedly reduced the number of bacteria colonizing the
      nematode intestine. To facilitate high throughput screening of compound
      libraries, we adapted a previously developed agar-based C. elegans-E. faecalis
      infection assay so that it could be carried out in liquid medium in standard 96
      well microtiter plates. We used this simple infection system to screen 6,000
      synthetic compounds and 1,136 natural product extracts. We identified 16
      compounds and 9 extracts that promoted nematode survival. Some of the compounds
      and extracts inhibited E. faecalis growth in vitro, but, in contrast to
      traditional antibiotics, the in vivo effective dose of many of these compounds
      was significantly lower than the minimum inhibitory concentration needed to
      prevent the growth of E. faecalis in vitro. Moreover, many of the compounds and
      extracts had little or no affect on in vitro bacterial growth. Our findings
      indicate that the whole-animal C. elegans screen identifies not only traditional
      antibiotics, but also compounds that target bacterial virulence or stimulate host
      defense.

PMID- 16801563
TI  - Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits
      as an atheroprotective mechanism.
AB  - We evaluated the effects of a 0.5% cholesterol-enriched diet (HCD) on nitric
      oxide synthase (NOS) and arginase expression and the modulating role of 17beta
      estradiol (E(2)) on this phenomenon. Thirty oopherectomized rabbits were divided
      into three groups and treated for 15 weeks. Group I received normal chow; group
      II, HCD; and group III, HCD plus E(2) pellets. Animals in group II showed an
      increase in plasma lipids, and they demonstrated atheromatous lesions as well as
      expression of arginase I and II accompanied by a significant number of BrdU
      positive cells in endothelial cells and intimal muscle cells, suggestive of an
      increase in cellular proliferation. There was significant expression of inducible
      NOS and increased staining of nitrotyrosine-positive areas. These were not
      observed in group I animals. In both groups, E(2) levels were low. In group III
      animals, E(2) supplementation led to a decrease in atheromatous lesions and BrdU
      positive cells and reduced expression of both inducible NOS and arginase I and II
      accompanied by a decrease in nitrotyrosine staining. E(2) levels were increased.
      Our results suggest that E(2) was responsible for these effects, despite the
      animals being hyperlipidemic, similar to those in group II. Because arginase is
      responsible for cell proliferation by converting l-arginine to polyamines, our
      results indicate that expression of arginase may play an important role in
      cellular proliferation in atherosclerosis, and inhibition of arginase expression
      by E(2) may be another potential mechanism in attenuating atherogenesis.

PMID- 16801564
TI  - Combined treatment with exercise training and acarbose improves metabolic control
      and cardiovascular risk factor profile in subjects with mild type 2 diabetes.
AB  - OBJECTIVE: The effect of exercise training and acarbose on glycemic control,
      insulin sensitivity, and phenotype was investigated in mild type 2 diabetes.
      RESEARCH DESIGN AND METHODS: Sixty-two men and women with type 2 diabetes were
      randomized to 12 weeks of structured exercise training with or without acarbose
      treatment or to acarbose alone. Glycemic control was determined by HbA(1c) (A1C),
      insulin sensitivity (M value) by euglycemic-hyperinsulinemic clamp, and regional
      fat distribution by computerized tomography and dual X-ray absorptiometry.
      Physical fitness was determined as maximal oxygen uptake (Vo(2max)). All
      investigations were performed before and after the intervention. RESULTS: Forty
      eight subjects completed the study. Exercise improved M value by 92% (P = 0.017)
      and decreased total and truncal fat (P = 0.002, 0.001) and systolic blood
      pressure (P = 0.01) but had no significant effect on Vo(2max) or A1C level. The
      combination of exercise and acarbose significantly decreased fasting plasma
      glucose, A1C, lipids, and diastolic blood pressure and increased Vo(2max),
      whereas effects on M value and body composition were comparable with that of
      exercise alone. Acarbose alone had no significant effect on either M value or A1C
      but decreased systolic (P = 0.001) and diastolic blood pressure (P = 0.001) and
      fasting proinsulin level (P = 0.009). Multiple regression analysis showed that
      addition of acarbose to exercise improved glycemic control. CONCLUSIONS: In
      subjects with mild type 2 diabetes, exercise training improved insulin
      sensitivity but had no effect on glycemic control. The addition of acarbose to
      exercise, however, was associated with significant improvement of glycemic
      control and possibly cardiovascular risk factors.

PMID- 16801565
TI  - Efficacy and safety of atorvastatin in the prevention of cardiovascular end
      points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of
      Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus
      (ASPEN).
AB  - OBJECTIVE: Cardiovascular disease (CVD) risk is increased in type 2 diabetes. The
      purpose of this study was to assess the effect of 10 mg of atorvastatin versus
      placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol
      levels below contemporary guideline targets. RESEARCH DESIGN AND METHODS:
      Subjects were randomly assigned to receive 10 mg of atorvastatin or placebo in a
      4-year, double-blind, parallel-group study. The composite primary end point
      comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke,
      recanalization, coronary artery bypass surgery, resuscitated cardiac arrest, and
      worsening or unstable angina requiring hospitalization. RESULTS: A total of 2,410
      subjects with type 2 diabetes were randomized. Mean LDL cholesterol reduction in
      the atorvastatin group over 4 years was 29% versus placebo (P < 0.0001). When we
      compared atorvastatin versus placebo, composite primary end point rates were 13.7
      and 15.0%, respectively (hazard ratio 0.90 [95% CI 0.73-1.12]). In the subset of
      1,905 subjects without prior myocardial infarction or interventional procedure,
      10.4% of atorvastatin- and 10.8% of placebo-treated subjects experienced a
      primary end point (0.97 [0.74-1.28]). In the 505 subjects with prior myocardial
      infarction or interventional procedure, 26.2% of atorvastatin- and 30.8% of
      placebo-treated subjects experienced a primary end point (0.82 [0.59-1.15]).
      Relative risk reductions in fatal and nonfatal myocardial infarction were 27%
      overall (P = 0.10) and 19% (P = 0.41) and 36% (P = 0.11) for subjects without and
      with prior myocardial infarction or interventional procedure, respectively.
      CONCLUSIONS: Composite end point reductions were not statistically significant.
      This result may relate to the overall study design, the types of subjects
      recruited, the nature of the primary end point, and the protocol changes required
      because of changing treatment guidelines. For these reasons, the results of the
      Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non
      Insulin-Dependent Diabetes Mellitus (ASPEN) did not confirm the benefit of
      therapy but do not detract from the imperative that the majority of diabetic
      patients are at risk of coronary heart disease and deserve LDL cholesterol
      lowering to the currently recommended targets.

PMID- 16801566
TI  - The effect of glucose variability on the risk of microvascular complications in
      type 1 diabetes.
AB  - OBJECTIVE: It is not known whether glycemic instability may confer a risk of
      microvascular complications that is in addition to that predicted by the mean
      blood glucose (MBG) value alone. This study has analyzed data from the Diabetes
      Control and Complications Trial (DCCT) to assess the effect of glucose
      variability on the risk of retinopathy and nephropathy in patients with type 1
      diabetes. RESEARCH DESIGN AND METHODS: Pre- and postprandial seven-point glucose
      profiles were collected quarterly during the DCCT in 1,441 individuals. The mean
      area under the curve glucose and the SD of glucose variability within 24 h and
      between visits were compared with the risk of retinopathy and nephropathy, having
      adjusted for age, sex, disease duration, treatment group, prevention cohort, and
      phase of treatment. RESULTS: Multivariate Cox regression showed that within-day
      and between-day variability in blood glucose around a patient's mean value has no
      influence on the development or progression of either retinopathy (P = 0.18 and P
      = 0.72, respectively) or nephropathy (P = 0.32 and P = 0.57). Neither preprandial
      (P = 0.18) nor postprandial (P = 0.31) glucose concentrations preferentially
      contribute to the probability of retinopathy. CONCLUSIONS: This study has shown
      that blood glucose variability does not appear to be an additional factor in the
      development of microvascular complications. Also, pre- and postprandial glucose
      values are equally predictive of the small-vessel complications of type 1
      diabetes.

PMID- 16801567
TI  - Glucose control influences glomerular filtration rate and its prediction in
      diabetic subjects.
AB  - OBJECTIVE: Hyperglycemia increases glomerular filtration rate (GFR), but the
      influence of HbA(1c) (A1C) on GFR and GFR's prediction by recommended equations
      remains to be determined. RESEARCH DESIGN AND METHODS: In 193 diabetic patients,
      we searched for an association between A1C and isotopically measured GFR (51Cr
      EDTA) and their predictions by the Cockcroft and Gault formula (CG) and the
      modification of diet in renal disease (MDRD) equation. Their accuracy for the
      diagnosis of moderate (GFR <60 ml/min per 1.73 m(2)) or severe (GFR <30 ml/min
      per 1.73 m(2)) renal failure was compared from receiver operating characteristic
      (ROC) curves, before and after categorizing the patients as well (A1C <or=8%) or
      poorly controlled. RESULTS: The mean GFR was 57.0 +/- 34.8 ml/min per 1.73 m(2)
      and was well correlated with both estimations (CG r = 0.75, MDRD r = 0.83; P <
      0.05). The areas under the ROC curves were higher with the MDRD (P < 0.05). A1C
      was correlated (P < 0.001) with the GFR (r = 0.29), MDRD (r = 0.38), CG (r =
      0.26), and the absolute differences between the GFR and their CG but not MDRD
      estimations (r = 0.17, P < 0.05). Each +1% A1C was associated with +6.0 ml/min
      per 1.73 m(2) GFR (CG +5.6, MDRD +5.3). After separating well-controlled (n = 88,
      A1C 7.0 +/- 0.7%) and poorly controlled (n = 105, 9.6 +/- 1.3%) patients, the
      diagnostic accuracies were better (P < 0.05) for the MDRD, except for the
      diagnosis of moderate renal failure in well-controlled patients (NS).
      CONCLUSIONS: GFR and its estimations correlate with A1C. Although the relations
      between GFR and its estimations were not affected by the degree of glucose
      control, the precision and diagnostic accuracy of the CG formula were diminished
      for A1C >8%. The MDRD equation was more accurate and robust in diabetic patients
      with impaired renal function.

PMID- 16801568
TI  - Impact of glycemic control on survival of diabetic patients on chronic regular
      hemodialysis: a 7-year observational study.
AB  - OBJECTIVE: To investigate the impact of glycemic control during regular
      hemodialysis on the survival of diabetic patients with chronic kidney disease
      (CKD) in a longitudinal observational study. RESEARCH DESIGN AND METHODS: A total
      of 114 diabetic CKD patients on hemodialysis at Inoue Hospital (Suita, Japan)
      were surveyed from May 1995 to December 2002 (survey period 45.5 +/- 29.3 [means
      +/- SD] months). All subjects were categorized into three groups by mean HbA(1c)
      (A1C) level during the 3-month period on hemodialysis preceding entry, as
      follows: good (A1C <6.5%, 5.7 +/- 0.4%, n = 34), fair (6.5 <or= A1C < 8.0%, 7.2
      +/- 0.4%, n = 39), and poor (A1C >or=8.0%, 9.2 +/- 0.9%, n = 41) A1C groups.
      RESULTS: There were no significant differences in age at entry, initiation of
      hemodialysis, duration of hemodialysis, blood pressure, cardiothoracic ratio,
      serum creatinine level, or hemoglobin level among the three groups. The
      cumulative survival of the poor A1C group during the survey was significantly
      lower than that of the fair and good A1C groups as determined by Kaplan-Meier
      estimation (P = 0.041, log-rank test). In a multivariate Cox proportional hazard
      model, both poor A1C group (hazard ratio 2.889, P = 0.010) and mean A1C (1.260
      per 1.0%, P = 0.003) were significant predictors of survival. CONCLUSIONS: In
      diabetic CKD patients on regular hemodialysis, poor glycemic control is an
      independent predictor of prognosis. This finding indicates the importance of
      careful management of glycemic control even after initiation of hemodialysis.

PMID- 16801570
TI  - Assessing the impact of visual acuity on quality of life in individuals with type
      2 diabetes using the short form-36.
AB  - OBJECTIVE: We sought to ascertain quality-of-life measures and utility values
      associated with visual acuity in type 2 diabetes. RESEARCH DESIGN AND METHODS:
      The Medical Outcome Study Short Form with 36 items (SF-36) was administered to
      4,051 individuals with type 2 diabetes who were enrolled in the Lipids in
      Diabetes Study, and their best attainable vision was determined using an Early
      Treatment of Diabetic Retinopathy Study chart, expressed as a LogMAR score. Eight
      domain scores and a utility value representing an overall quality-of-life score
      were calculated using predefined algorithms. The associations between quality of
      life measured and best-eye visual acuity were assessed graphically and by
      regression analysis. RESULTS: All eight SF-36 domain scores were negatively
      associated with reduced visual acuity. The impact of lower levels of visual
      acuity ranged from a decline of 1.3 units for a 0.1-LogMAR increase for physical
      functioning and 0.6 units in mental health. Regression analysis indicated a
      negative association (P < 0.001) between utility and reduced visual acuity after
      controlling for sex, BMI, smoking status, and history of diabetes complications.
      Patients whose LogMAR scores equated to legally blind had, on average, 0.054 (95%
      CI 0.034-0.074) lower utility compared with patients with normal visual acuity.
      CONCLUSIONS: Reduced visual acuity is negatively associated with quality of life.
      The utility scores estimated here should inform studies quantifying the burden of
      diabetes and those evaluating potential therapies for treating or preventing
      diabetic eye diseases.

PMID- 16801569
TI  - Dietary fibers and glycemic load, obesity, and plasma adiponectin levels in women
      with type 2 diabetes.
AB  - OBJECTIVE: The purpose of this study was to examine the associations of dietary
      fibers and glycemic load with plasma adiponectin in diabetic women and
      investigate the modification effect of obesity. RESEARCH DESIGN AND METHODS: We
      conducted a cross-sectional analysis in 902 women with type 2 diabetes from the
      Nurses' Health Study. Dietary information was obtained using semiquantitative
      food frequency questionnaires. RESULTS: After adjustment for age, smoking,
      alcohol consumption, physical activity, aspirin use, HbA(1c), history of
      hypertension and hypercholesterolemia, and postmenopausal hormone use, intakes of
      cereal fiber and fruit fiber (P for trend = 0.002 and 0.036, respectively) were
      significantly associated with an increasing trend of plasma adiponectin
      concentrations. Further adjustment for BMI did not appreciably change the
      associations for cereal fiber but attenuated the associations for fruit fiber.
      Adiponectin concentrations were 24% higher in the highest compared with the
      lowest quintile of cereal fiber. Dietary glycemic load and glycemic index were
      significantly associated with lower plasma adiponectin levels, after adjustment
      for BMI and other covariates (P for trend = 0.01 and 0.03, respectively). The
      percent differences in adiponectin concentration between the highest and the
      lowest quintiles of dietary glycemic load and glycemic index were 17 and 18%,
      respectively. The associations between dietary factors and plasma adiponectin
      were consistent across lean (BMI <25 kg/m(2)), overweight (25 <or= BMI <30
      kg/m(2)), and obese subjects (BMI >or=30 kg/m(2)). CONCLUSIONS: Our data indicate
      that dietary cereal fiber and glycemic load/index are associated with the
      circulating adiponectin concentration. Such associations were not modified by
      obesity status.

PMID- 16801571
TI  - Continuous glucose monitoring-guided insulin adjustment in children and
      adolescents on near-physiological insulin regimens: a randomized controlled
      trial.
AB  - OBJECTIVE: This randomized controlled trial assesses the effect on glycemic
      control of continuous glucose monitoring system (CGMS)-guided insulin therapy
      adjustment in young people with type 1 diabetes on intensive diabetes treatment
      regimens with continuous subcutaneous insulin infusion (CSII) or glargine.
      RESEARCH DESIGN AND METHODS: Pediatric subjects were recruited if they had an
      HbA(1c) (A1C) <10% and had been on CSII or glargine for at least 3 months. Thirty
      six subjects were randomized to insulin adjustment on the basis of 72 h of CGMS
      every 3 weeks or intermittent self-monitoring of blood glucose (SMBG) for 3
      months. A1C and fructosamine were measured at baseline and 6 and 12 weeks. Follow
      up A1C was measured at 6 months. Mean baseline A1C was 8.2% (n = 19) in the CGMS
      group and 7.9% (n = 17) in the control group. RESULTS: There was a significant
      improvement in A1C from baseline values in both groups, but there was no
      difference in the degree of improvement in A1C at 12 weeks between the CGMS (
      0.4% [95% CI -0.7 to -0.1]) and the control group (-0.4% [-0.8 to 0.2]). In the
      CGMS group, improved A1C was at the cost of increased duration of hypoglycemia.
      CONCLUSIONS: CGMS is no more useful than intermittent fingerstick SMBG and
      frequent review in improving diabetes control in reasonably well-controlled
      patients on near-physiological insulin regimens when used in an outpatient clinic
      setting.

PMID- 16801572
TI  - The prevalence, severity, and impact of painful diabetic peripheral neuropathy in
      type 2 diabetes.
AB  - OBJECTIVE: To determine the prevalence of painful diabetic peripheral neuropathy
      (PDPN) in a population-based sample and to estimate its severity and impact.
      RESEARCH DESIGN AND METHODS: A cross-sectional descriptive study consisting of
      two phases: phase 1, a postal survey to patients with type 2 diabetes (an initial
      screening questionnaire including one question about pain); phase 2, neurological
      history and examination using the Toronto Clinical Scoring System. Subjects with
      PDPN or mixed (PDPN and nonneuropathic) pain completed the Neuropathic Pain Scale
      and Neuroqol to assess severity and nature of the pain and impact on quality of
      life. Those without PDPN completed the Neuroqol only. RESULTS: In phase 1, there
      was a 92.7% response (n = 326), with 208 (63.8%) subjects reporting pain. In
      phase 2, 269 (82.5%) subjects attended and 51 (19.0%) were found to have PDPN: 99
      (36.8%) nonneuropathic pain, 20 (7.4%) mixed pain, and 99 (36.8%) no pain (PDPN
      prevalence 26.4%). Of those with PDPN, 80% stated that their pain was moderate or
      severe. Those affected had poorer quality of life than those with no pain
      (difference in mean scores 3.6 [95% CI 2.5-4.6%]) compared with those with
      nonneuropathic pain (1.7 [0.4-2.9%]). Both pain and neuropathy score were
      independently associated with quality of life, and subjects with PDPN had
      significantly higher neuropathy scores. CONCLUSIONS: Our study showed a
      prevalence of PDPN of 26.4%. Having PDPN has a significant negative effect on
      quality of life, and increasing neuropathy is associated with an increasing risk
      of developing PDPN.

PMID- 16801573
TI  - Blood pressure and hematocrit in diabetes and the role of endothelial responses
      in the variability of blood viscosity.
AB  - OBJECTIVE: To investigate the relationship between mean arterial blood pressure
      and hematocrit in a population of treated diabetic patients and a control
      population of healthy individuals. RESEARCH DESIGN AND METHODS: Data on
      hematocrit and blood pressure were obtained from 129 diabetic subjects (87 women
      and 42 men) and 103 healthy subjects (76 women and 27 men) enrolled in a cross
      sectional study. Alcohol consumption, ischemic heart disease, stroke, neoplasia,
      renal, hepatic, and chronic inflammatory disease were exclusion criteria.
      RESULTS: The hematocrit of diabetic patients ranged from 0.35 to 0.52, and blood
      pressure had a bimodal distribution described by a second-order polynomial (P <
      0.001), whereby elevated pressures correlated with low and high hematocrit, while
      the minimum average pressure was at hematocrit 0.43. Hematocrit of normal control
      subjects (range 0.28-0.55) was uncorrelated to blood pressure (averaged 99.7 +/-
      9.7 mmHg). High blood pressure, low hematocrit diabetic subjects up to the
      minimum average hematocrit of 0.43 had a negative correlation (P < 0.0001)
      between these variables. CONCLUSIONS: Our findings are compatible with the
      hypothesis that diabetic patients present normal responses to hematocrit
      variation and therefore blood viscosity and shear stress in mediating the release
      of vasodilators and lack the ability to autoregulate blood pressure relative to
      differences in hematocrit by comparison to nondiabetic subjects. These findings
      also suggest that the treatment of diabetes should target maintaining an optimal
      hematocrit in order to lower cardiovascular risk.

PMID- 16801574
TI  - Cerebral blood flow velocity and periventricular white matter hyperintensities in
      type 2 diabetes.
AB  - OBJECTIVE: Diabetes increases the risk for cerebromicrovascular disease, possibly
      through its effects on blood flow regulation. The aim of this study was to assess
      the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle
      cerebral arteries and to determine the relationship between white matter
      hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs. RESEARCH
      DESIGN AND METHODS: We measured BFVs in 28 type 2 diabetic and 22 control
      subjects (aged 62.3 +/- 7.2 years) using transcranial Doppler ultrasound during
      baseline, hyperventilation, and CO(2) rebreathing. WMHs were graded, and their
      volume was quantified from fluid-attenuated inversion recovery images on a 3.0
      Tesla MRI. RESULTS: The diabetic group demonstrated decreased mean BFVs and
      increased cerebrovascular resistance during baseline, hypo- and hypercapnia (P <
      0.0001), and impaired CO(2) reactivity (P = 0.05). WMH volume was negatively
      correlated with baseline BFV (P < 0.0001). A regression model revealed that
      baseline BFVs were negatively associated with periventricular WMHs, HbA(1c)
      (A1C), and inflammatory markers and positively associated with systolic blood
      pressure (R(2) = 0.86, P < 0.0001). CONCLUSIONS: Microvascular disease in type 2
      diabetes, which manifests as white matter abnormalities on MRI, is associated
      with reduced cerebral BFVs, increased resistance in middle cerebral arteries, and
      inflammation. These findings are clinically relevant as a potential mechanism for
      cerebrovascular disease in elderly with type 2 diabetes.

PMID- 16801575
TI  - IGF-binding protein-1 levels are related to insulin-mediated glucose disposal and
      are a potential serum marker of insulin resistance.
AB  - OBJECTIVE: IGF-binding protein (IGFBP)-1 is negatively regulated by insulin. We
      determined whether the measurement of IGFBP-1 in serum is a useful marker of
      insulin resistance. RESEARCH DESIGN AND METHODS: Twenty-three subjects underwent
      a euglycemic insulin clamp. Glucose disposal rates (M) were then correlated with
      measurements of IGFBP-1, fasting insulin levels, homeostasis model assessment
      (HOMA), and BMI. RESULTS: IGFBP-1 levels more strongly correlated with M (R =
      0.73) than the other parameters such as BMI or HOMA. The level of this protein
      decreased in individuals who became more insulin sensitive by exercise training.
      CONCLUSIONS: These studies show a strong correlation between insulin sensitivity
      and the serum levels of IGFBP-1. These studies suggest, therefore, that
      measurement of this protein may be valuable in identifying those individuals with
      insulin resistance and those individuals who respond to interventional
      strategies.

PMID- 16801576
TI  - Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on
      diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose
      Reductase Inhibitor-Diabetes Complications Trial.
AB  - OBJECTIVE: We sought to evaluate the long-term efficacy and safety of epalrestat,
      an aldose reductase inhibitor, on diabetic peripheral neuropathy. RESEARCH DESIGN
      AND METHODS: Subjects with diabetic neuropathy, median motor nerve conduction
      velocity (MNCV) >or=40 m/s, and HbA(1c) <or=9% were enrolled in this open-label,
      multicenter study and randomized to 150 mg/day epalrestat or a control group.
      After excluding the withdrawals, 289 (epalrestat group) and 305 (control group)
      patients were included in the analyses. The primary end point was change from
      baseline in median MNCV at 3 years. Secondary end points included assessment of
      other somatic nerve function parameters (minimum F-wave latency [MFWL] of the
      median motor nerve and vibration perception threshold [VPT]), cardiovascular
      autonomic nerve function, and subjective symptoms. RESULTS: Over the 3-year
      period, epalrestat prevented the deterioration of median MNCV, MFWL, and VPT seen
      in the control group. The between-group difference in change from baseline in
      median MNCV was 1.6 m/s (P < 0.001). Although a benefit with epalrestat was
      observed in cardiovascular autonomic nerve function variables, this did not reach
      statistical significance compared with the control group. Numbness of limbs,
      sensory abnormality, and cramping improved significantly with epalrestat versus
      the control group. The effects of epalrestat on median MNCV were most evident in
      subjects with better glycemic control and with no or mild microangiopathies.
      CONCLUSIONS: Long-term treatment with epalrestat is well tolerated and can
      effectively delay the progression of diabetic neuropathy and ameliorate the
      associated symptoms of the disease, particularly in subjects with good glycemic
      control and limited microangiopathy.

PMID- 16801577
TI  - Effect of peroxisome proliferator-activated receptor gamma agonist treatment on
      subclinical atherosclerosis in patients with insulin-requiring type 2 diabetes.
AB  - OBJECTIVE: To determine the effect of thiazolidinedione treatment on subclinical
      atherosclerosis progression in insulin-requiring patients with clinical
      characteristics suggesting type 2 diabetes. RESEARCH DESIGN AND METHODS: Eligible
      participants (n = 299) were randomized within strata of baseline common carotid
      artery (CCA) intima-media thickness (IMT) (<0.8 mm, >or=0.8 mm) to 400 mg
      troglitazone daily or placebo for 2 years. A general linear mixed-effects model
      was used to compare the rate of change in CCA-IMT between treatment groups.
      RESULTS: Overall, average rates of CCA-IMT change were not significantly
      different between troglitazone- and placebo-treated subjects (0.0030 +/- 0.021
      vs. 0.0066 +/- 0.021 mm/year; P = 0.17). In the stratum of subjects with CCA-IMT
      >or=0.8 mm, troglitazone significantly reduced the progression of CCA-IMT
      relative to placebo (0.0013 +/- 0.022 vs. 0.0084 +/- 0.023 mm/year; P = 0.03).
      Fasting glucose, insulin, and HbA(1c) were significantly lower in troglitazone-
      versus placebo-treated subjects (P < 0.01). Whereas blood pressure significantly
      differed between treatment groups in the >or=0.8-mm stratum, there was no
      difference between treatment groups in the <0.8-mm stratum. CONCLUSIONS: Insulin
      sensitization and reduction in blood pressure may be contributory mechanisms by
      which troglitazone reduced subclinical atherosclerosis progression in this cohort
      of well-controlled insulin-dependent patients with clinical characteristics
      suggesting type 2 diabetes.

PMID- 16801578
TI  - Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by
      islet hyperplasia or increased beta-cell turnover.
AB  - OBJECTIVE: The purpose of this study was to establish whether hypoglycemia after
      gastric bypass surgery (GBS) for morbid obesity is due to increased fractional
      beta-cell area or inappropriately increased insulin secretion. RESEARCH DESIGN
      AND METHODS: We examined pancreata obtained at partial pancreatectomy from 6
      patients with post-GBS hypoglycemia and compared these with 31 pancreata from
      obese subjects and 16 pancreata from lean control subjects obtained at autopsy.
      We addressed the following questions. In patients with post-GBS hypoglycemia, is
      beta-cell area increased and is beta-cell formation increased or beta-cell
      apoptosis decreased? RESULTS: We report that in patients with post-GBS
      hypoglycemia, beta-cell area was not increased compared with that in obese or
      even lean control subjects. Consistent with this finding, there was no evidence
      of increased beta-cell formation (islet neogenesis and beta-cell replication) or
      decreased beta-cell loss in patients with post-GBS hypoglycemia. In control
      subjects, mean beta-cell nuclear diameter correlated with BMI (r(2) = 0.79, P <
      0.001). In patients with post-GBS hypoglycemia, beta-cell nuclear diameter was
      increased (P < 0.001) compared with that for BMI in matched control subjects but
      was appropriate for BMI before surgery. CONCLUSIONS: We conclude that post-GBS
      hypoglycemia is not due to increases in beta-cell mass or formation. Rather,
      postprandial hypoglycemia after GBS is due to a combination of gastric dumping
      and inappropriately increased insulin secretion, either as a failure to
      adaptively decrease insulin secretion after GBS or as an acquired phenomenon.

PMID- 16801579
TI  - Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase
      in intrarenal vascular disease?
AB  - OBJECTIVE: To investigate the role of intrarenal vascular disease in the
      pathogenesis of nonalbuminuric renal insufficiency in type 2 diabetes. RESEARCH
      DESIGN AND METHODS: We studied 325 unselected clinic patients who had sufficient
      clinical and biochemical information to calculate an estimated glomerular
      filtration rate (eGFR) using the Modified Diet in Renal Disease six-variable
      formula, at least two estimations of urinary albumin excretion rates (AER), and a
      renal duplex scan to estimate the resistance index of the interlobar renal
      arteries. The resistance index, measured as part of a complications surveillance
      program, was compared in patients with an eGFR < or >or=60 ml/min per 1.73 m(2)
      who were further stratified into normo- (AER <20), micro- (20-200), or
      macroalbuminuria (> 200 microg/min) categories. RESULTS: Patients with an eGFR
      <60 ml/min per 1.73 m(2) had a higher resistance index of the renal interlobar
      arteries compared with patients with an eGFR >or=60 ml/min per 1.73 m(2).
      However, the resistance index was elevated to a similar extent in patients with
      an eGFR <60 ml/min per 1.73 m(2) regardless of albuminuric status (normo- 0.74 +/
      0.01, micro- 0.73 +/- 0.01, and macroalbuminuria resistance index 0.75 +/-
      0.11). Multiple regression analysis revealed that increased age (P < 0.0001),
      elevated BMI (P = 0.0001), decreased eGFR (P < 0.01), and decreased diastolic
      blood pressure (P < 0.01), but not an increased AER, were independently
      associated with an elevated resistance index in patients with impaired renal
      function. CONCLUSIONS: Subjects with type 2 diabetes and reduced glomerular
      filtration rate had similar degrees of intrarenal vascular disease, as measured
      by the intrarenal arterial resistance index, regardless of their AER status. The
      pathological mechanisms that determine the relationship between impaired renal
      function and AER status in subjects with type 2 diabetes remain to be elucidated.

PMID- 16801580
TI  - Physical activity, cardiovascular fitness, and insulin sensitivity among U.S.
      adolescents: the National Health and Nutrition Examination Survey, 1999-2002.
AB  - OBJECTIVE: The purpose of this study was to examine the association of physical
      activity and cardiovascular fitness (CVF) with insulin sensitivity in a
      nationally representative sample of U.S. youth. RESEARCH DESIGN AND METHODS: The
      study included 1,783 U.S. adolescents (11% Mexican American, 14% non-Hispanic
      black, 63% non-Hispanic white, and 12% other) aged 12-19 years who were examined
      in the 1999-2002 National Health and Nutrition Examination Survey. Physical
      activity was assessed by questionnaire and expressed in units of MET hours per
      week. Predicted maximal oxygen uptake (Vo(2max), expressed in milliliters per
      kilogram of body weight per minute), a measure of CVF, was determined by a
      submaximal multistage treadmill test. Insulin sensitivity was defined by the
      Quantitative Insulin Sensitivity Check Index. RESULTS: Boys were more likely than
      girls to be highly active (>or=30 MET h/week; 51 vs. 37%, P < 0.001) and had
      higher levels of CVF (mean Vo(2max) 47 vs. 39 ml x kg(-1) x min(-1), P < 0.001).
      Sex-specific multiple regression models controlled for age, race/ethnicity, and
      BMI showed that in boys, high levels of physical activity and high levels of CVF
      were significantly and positively associated with insulin sensitivity (beta =
      0.84, P < 0.001 and beta = 0.82, P = 0.01, respectively). Among girls, insulin
      sensitivity was not significantly associated with physical activity or with CVF
      but was inversely and significantly associated with BMI. CONCLUSIONS: Increasing
      physical activity and CVF may have an independent effect of improving insulin
      sensitivity among boys. For girls, the primary role of physical activity may be
      in weight maintenance.

PMID- 16801581
TI  - Prospective study of diabetes and risk of hip fracture: the Nurses' Health Study.
AB  - OBJECTIVE: The purpose of this study was to determine whether women with type 1
      and type 2 diabetes are at higher risk of hip fractures. RESEARCH DESIGN AND
      METHODS: A total of 109,983 women aged 34-59 years in 1980 were followed through
      2002 for the occurrence of hip fracture. At baseline and through biennial follow
      up, women were asked about their history and treatment of diabetes and other
      potential risk factors for hip fracture. RESULTS: During 2.22 million person
      years of follow-up, 1,398 women had a hip fracture. Compared with women without
      diabetes, the age-adjusted relative risk (RRs) of hip fracture was 7.1 (95% CI
      4.4-11.4) for women with type 1 diabetes and 1.7 (1.4-2.0) for those with type 2
      diabetes. After further adjustment for BMI, smoking, physical activity,
      menopausal status, daily intake of calcium, vitamin D, protein, and
      postmenopausal hormone use, the multivariate RR of incident hip fracture in
      individuals with type 1 diabetes compared with individuals without diabetes was
      6.4 (3.9-10.3) and with type 2 diabetes was 2.2 (1.8-2.7). The RRs increased with
      longer duration of type 2 diabetes (3.1 [2.3-4.0] for >or=12 years compared with
      no diabetes, P for trend < 0.001) and ever use of insulin. CONCLUSIONS: These
      data indicate that both type 1 and type 2 diabetes are associated with an
      increased risk of hip fracture. The results of this study highlight the need for
      fracture-prevention strategies in women with diabetes.

PMID- 16801582
TI  - A prospective study of dairy intake and the risk of type 2 diabetes in women.
AB  - OBJECTIVE: Although studies have indicated that increased dairy intake may reduce
      risk of overweight and insulin resistance syndrome, data directly relating dairy
      intake to type 2 diabetes remain sparse. RESEARCH DESIGN AND METHODS: We
      prospectively examined the associations between intake of dairy foods and calcium
      and incident type 2 diabetes in 37,183 women without a history of diabetes,
      cardiovascular disease, and/or cancer at baseline. RESULTS: During an average of
      10 years of follow-up, we documented 1,603 incident cases. After adjusting for
      potential confounders including BMI, smoking status, physical activity, family
      history of diabetes, alcohol consumption, history of hypertension, use of
      hormones, and high cholesterol, the relative risk for type 2 diabetes among women
      in the highest quintile of dairy intake was 0.79 (95% CI 0.67-0.94; P for trend =
      0.007) compared with those in the lowest quintile. Each serving-per-day increase
      in dairy intake was associated with a 4% lower risk (0.96 [0.93-1.01]). The
      inverse association with type 2 diabetes appeared to be mainly attributed to low
      fat dairy intake; the multivariate relative risks comparing the highest to the
      lowest quintiles was 0.79 (0.67-0.93; P for trend = 0.002) for low-fat dairy. The
      inverse relation between dairy intake and incident type 2 diabetes remained
      unchanged after further adjustment for dietary calcium, vitamin D, glycemic load,
      fat, fiber, and magnesium intake. These associations also did not vary
      significantly according to BMI. CONCLUSIONS: A dietary pattern that incorporates
      higher low-fat dairy products may lower the risk of type 2 diabetes in middle
      aged or older women.

PMID- 16801583
TI  - Ethnicity, obesity, and risk of type 2 diabetes in women: a 20-year follow-up
      study.
AB  - OBJECTIVE: To examine ethnic differences in risk of type 2 diabetes, taking
      dietary and lifestyle risk factors into account. RESEARCH DESIGN AND METHODS: A
      prospective (1980-2000) cohort (from The Nurses' Health Study) including 78,419
      apparently healthy women (75,584 whites, 801 Asians, 613 Hispanics, and 1,421
      blacks) was studied. Detailed dietary and lifestyle information for each
      participant was repeatedly collected every 4 years. RESULTS: During 1,294,799
      person-years of follow-up, we documented 3,844 incident cases of diabetes.
      Compared with whites, the age-adjusted relative risks (RRs) were 1.43 (95% CI
      1.08-1.90) for Asians, 1.76 (1.32-2.34) for Hispanics, and 2.18 (1.82-2.61) for
      blacks. After adjustment for BMI, the RRs changed to 2.26 (1.70-2.99) for Asians,
      1.86 (1.40-2.47) for Hispanics, and 1.34 (1.12-1.61) for blacks. For each 5-unit
      increment in BMI, the multivariate RR of diabetes was 2.36 (1.83-3.04) for
      Asians, 2.21 (1.75-2.79) for Hispanics, 1.96 (1.93-2.00) for whites, and 1.55
      (1.36-1.77) for blacks (P for interaction <0.001). For each 5-kg weight gain
      between age 18 and the year 1980, the risk of diabetes was increased by 84% (95%
      CI 58-114) for Asians, 44% (26-63) for Hispanics, 38% (28-49) for blacks, and 37%
      (35-38%) for whites. A healthy diet high in cereal fiber and polyunsaturated fat
      and low in trans fat and glycemic load was more strongly associated with a lower
      risk of diabetes among minorities (RR 0.54 [95% CI 0.39-0.73]) than among whites
      (0.77 [0.72-0.84]). CONCLUSIONS: The risk of diabetes is significantly higher
      among Asians, Hispanics, and blacks than among whites before and after taking
      into account differences in BMI. Weight gain is particularly detrimental for
      Asians. Our data suggest that the inverse association of a healthy diet with
      diabetes is stronger for minorities than for whites.

PMID- 16801584
TI  - The metabolic syndrome is frequent in Klinefelter's syndrome and is associated
      with abdominal obesity and hypogonadism.
AB  - OBJECTIVE: Klinefelter's syndrome is associated with an increased prevalence of
      diabetes, but the pathogenesis is unknown. Accordingly, the aim of this study was
      to investigate measures of insulin sensitivity, the metabolic syndrome, and sex
      hormones in patients with Klinefelter's syndrome and an age-matched control
      group. RESEARCH DESIGN AN METHODS: In a cross-sectional study, we examined 71
      patients with Klinefelter's syndrome, of whom 35 received testosterone treatment,
      and 71 control subjects. Body composition was evaluated using dual-energy X-ray
      absorptiometry scans. Fasting blood samples were analyzed for sex hormones,
      plasma glucose, insulin, C-reactive protein (CRP), and adipocytokines. We
      analyzed differences between patients with untreated Klinefelter's syndrome and
      control subjects and subsequently analyzed differences between testosterone
      treated and untreated Klinefelter's syndrome patients. RESULTS: Of the patients
      with Klinefelter's syndrome, 44% had metabolic syndrome (according to National
      Cholesterol Education Program/Adult Treatment Panel III criteria) compared with
      10% of control subjects. Insulin sensitivity (assessed by homeostasis model
      assessment 2 modeling), androgen, and HDL cholesterol levels were significantly
      decreased, whereas total fat mass and LDL cholesterol, triglyceride, CRP, leptin,
      and fructosamine levels were significantly increased in untreated Klinefelter's
      syndrome patients. In treated Klinefelter's syndrome patients, LDL cholesterol
      and adiponectin were significantly decreased, whereas no difference in body
      composition was found in comparison with untreated Klinefelter's syndrome
      patients. Multivariate analyses showed that truncal fat was the major determinant
      of metabolic syndrome and insulin sensitivity. CONCLUSIONS: The prevalence of
      metabolic syndrome was greatly increased, whereas insulin sensitivity was
      decreased in Klinefelter's syndrome. Both correlated with truncal obesity.
      Hypogonadism in Klinefelter's syndrome may cause an unfavorable change in body
      composition, primarily through increased truncal fat and decreased muscle mass.
      Testosterone treatment in Klinefelter's syndrome only partly corrected the
      unfavorable changes observed in untreated Klinefelter's syndrome, perhaps due to
      insufficient testosterone doses.

PMID- 16801585
TI  - Are obesity-related metabolic risk factors modulated by the degree of insulin
      resistance in adolescents?
AB  - OBJECTIVE: Obesity is often associated with insulin resistance and the components
      of the metabolic syndrome. However, wide variations in insulin sensitivity are
      noted in obese youth. It is not clear if greater insulin resistance confers a
      higher risk of cardiovascular comorbidities and risk for type 2 diabetes.
      RESEARCH DESIGN AND METHODS: We investigated physical and metabolic features of
      54 obese adolescents. Subsequently, we pair matched 17 moderately insulin
      resistant (MIR group) to 17 severely insulin-resistant (SIR group) youth based on
      cut points for insulin sensitivity (MIR group insulin sensitivity within 2 SDs
      and SIR group <2 SDs of normal-weight adolescent values). We evaluated
      differences in body composition (dual-energy X-ray absorptiometry), abdominal fat
      (computed tomography scan), cardiorespiratory fitness (CRF) (Vo(2max) on a
      treadmill), insulin sensitivity and secretion (hyperinsulinemic-euglycemic and
      hyperglycemic clamps), substrate utilization (indirect calorimetry), and fasting
      adiponectin and lipid profile. RESULTS: SIR youth had higher visceral adiposity
      (78.3 +/- 6.9 vs. 60.3 +/- 6.9 cm(2), P = 0.017) and waist-to-hip ratio (0.91 +/-
      0.01 vs. 0.86 +/- 0.02, P = 0.026) and lower HDL (1.0 +/- 0.03 vs. 1.16 +/- 0.06
      mmol/l, P = 0.015) than pair-matched MIR subjects. There was a tendency for
      adiponectin (6.1 +/- 0.5 vs. 8.6 +/- 1.1 microg/ml, P = 0.079) and CRF (49.9 +/-
      3.2 vs. 55.2 +/- 3.5 ml x min(-1) x kg(-1) fat-free mass, P = 0.09) to be lower
      in SIR subjects. SIR youth also had an impaired balance between insulin
      sensitivity and beta-cell compensation with a lower glucose disposition index.
      CONCLUSIONS: Despite similar BMI, the degree of insulin resistance impacts the
      risk for obesity-related metabolic comorbidities. The SIR youth are at greater
      risk for type 2 diabetes and cardiovascular disease.

PMID- 16801586
TI  - Promoting physical activity in a low-income multiethnic district: effects of a
      community intervention study to reduce risk factors for type 2 diabetes and
      cardiovascular disease: a community intervention reducing inactivity.
AB  - OBJECTIVE: The aim was to assess the net effects on risk factors for type 2
      diabetes and cardiovascular disease of a community-based 3-year intervention to
      increase physical activity. RESEARCH DESIGN AND METHODS: A pseudo-experimental
      cohort design was used to compare changes in risk factors from an intervention
      and a control district with similar socioeconomic status in Oslo, Norway, using a
      baseline investigation of 2,950 30- to 67-year-old participants and a follow-up
      investigation of 1,776 (67% of those eligible, 56% women, 18% non-Western
      immigrants) participants. A set of theory-based activities to promote physical
      activity were implemented and tailored toward groups with different psychosocial
      readiness for change. All results reported are net changes (the difference
      between changes in the intervention and control districts). At both surveys, the
      nonfasting serum levels of lipids and glucose were adjusted for time since last
      meal. RESULTS: The increase in physical activity measured by two self-reported
      questionnaires was 9.5% (P = 0.008) and 8.1% (P = 0.02), respectively. The
      proportion who increased their body mass was 14.2% lower in the intervention
      district (P < 0.001), implying a 50% relative reduction compared with the control
      district, and was lower across subgroups. Beneficial effects were seen for
      triglyceride levels (0.16 mmol/l [95% CI 0.06-0.25], P = 0.002), cholesterol-to
      HDL cholesterol ratio (0.12 [0.03-0.20], P = 0.007), systolic blood pressure (3.6
      mmHg [2.2-4.8], P < 0.001), and for men also in glucose levels (0.35 mmol/l [0.03
      0.67], P = 0.03). The net proportion who were quitting smoking was 2.9% (0.1-5.7,
      P = 0.043). CONCLUSIONS: Through a theory-driven, low-cost, population-based
      intervention program, we observed an increase in physical activity levels,
      reduced weight gain, and beneficial changes in other risk factors for type 2
      diabetes and cardiovascular disease.

PMID- 16801587
TI  - Risk of progression to type 2 diabetes based on relationship between postload
      plasma glucose and fasting plasma glucose.
AB  - OBJECTIVE: We sought to assess the risk of progression to type 2 diabetes in
      normal glucose tolerance (NGT) subjects based on the relationship between the
      plasma glucose concentration during oral glucose tolerance tests (OGTTs) and the
      fasting plasma glucose (FPG) concentration. RESEARCH DESIGN AND METHODS: Subjects
      with NGT (n = 1,282) from the San Antonio Heart Study received an OGTT with
      measurement of the plasma glucose concentration at 0, 30, 60, and 120 min at
      baseline and after 7-8 years of follow-up. Subjects were divided into four groups
      based on the relationship between the plasma glucose concentration during the
      OGTT and the FPG concentration on the same day as the OGTT. Insulin resistance
      was calculated by the homeostasis model assessment of insulin resistance (HOMA
      IR) and Matsuda index. Early-phase insulin secretion was calculated as the ratio
      between the incremental plasma insulin and glucose concentrations during the
      first 30 min of the OGTT (DeltaI(0-30)/DeltaG(0-30)). Total insulin secretion was
      calculated as the ratio between the incremental areas under the insulin and
      glucose curves during the OGTT [DeltaG(AUC)/DeltaI(AUC)]. RESULTS: In 23 subjects
      (group I), the plasma glucose concentration during the OGTT returned to levels
      below the FPG concentration at 30 min; in 111 subjects (group II) and in 313
      subjects (group III), the plasma glucose concentration during the OGTT returned
      to levels below the FPG concentration at 60 and 120 min, respectively. In the
      remaining 835 subjects (group IV), the plasma glucose concentration during the
      OGTT never fell below the FPG concentration. Insulin resistance, measured by HOMA
      IR and the Matsuda index, increased progressively from group I through group IV,
      while insulin secretion measured by DeltaI(0-30)/DeltaG(0-30) and
      DeltaG(AUC)/DeltaI(AUC) decreased progressively from group I through group IV.
      The incidence of type 2 diabetes was 0% in group I and progressively increased to
      0.9% in group II, 3.2% in group III, and 6.4% in group IV. CONCLUSIONS: Subjects
      whose postload plasma glucose concentration returned to baseline (i.e., FPG
      level) more quickly had greater insulin sensitivity, a higher insulinogenic
      index, and a lower risk of developing type 2 diabetes after 8 years of follow-up
      compared with subjects whose postload glucose concentration returned to baseline
      more slowly.

PMID- 16801588
TI  - Use of HbA1c in predicting progression to diabetes in French men and women: data
      from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR).
AB  - OBJECTIVE: Early identification of subjects at high risk for diabetes is
      essential, and random HbA(1c) (A1C) may be more practical than fasting plasma
      glucose (FPG). The predictive value of A1C, in comparison to FPG, is evaluated
      for 6-year incident diabetes. RESEARCH DESIGN AND METHODS: From the French cohort
      study Data from an Epidemiological Study on the Insulin Resistance Syndrome
      (DESIR), 1,383 men and 1,437 women, aged 30-65 years, were volunteers for a
      routine health check-up. Incident diabetes was defined by FPG >or=7.0 mmol/l or
      treatment by antidiabetic drugs. Multivariate logistic regression models were
      used to predict diabetes at 6 years. Receiver operating characteristic curves
      compared the predictive values of A1C and FPG. RESULTS: At 6 years, 30 women
      (2.1%) and 60 men (4.3%) had developed diabetes. Diabetes risk increased
      exponentially with A1C in both sexes (P < 0.001). After stratifying on FPG, A1C
      predicted diabetes only in subjects with impaired fasting glucose (IFG) (FPG
      >or=6.10 mmol/l): the odds ratio (95% CI) for a 1% increase in A1C was 7.20 (3.00
      17.00). In these subjects, an A1C of 5.9% gave an optimal sensitivity of 64% and
      specificity of 77% to predict diabetes. CONCLUSIONS: A1C predicted diabetes, even
      though the diagnosis of diabetes was based on FPG, but it was less sensitive and
      specific than FPG. It could be used as a test if fasting blood sampling was not
      available or in association with FPG. In subjects with IFG, A1C is better than
      glucose to evaluate diabetes risk, and it could be used to select subjects for
      intensive early intervention.

PMID- 16801589
TI  - Hypoadiponectinemia and proinflammatory state: two sides of the same coin?:
      results from the Cooperative Health Research in the Region of Augsburg Survey 4
      (KORA S4).
AB  - OBJECTIVE: Previous studies have yielded conflicting results on the association
      of adiponectin levels and inflammation. Low systemic concentrations of
      adiponectin, as well as elevated levels of immune mediators, represent risk
      factors for the development of type 2 diabetes and coronary artery disease. The
      major aim of this cross-sectional study was to investigate the interdependence of
      hypoadiponectinemia and low-grade systemic inflammation. RESEARCH DESIGN AND
      METHODS: The study sample consisted of 606 participants aged 55-74 years (244
      with normal glucose tolerance, 242 with impaired glucose tolerance, and 120 with
      newly diagnosed type 2 diabetes) of the population-based KORA S4 (Cooperative
      Health Research in the Region of Augsburg Survey 4; 1999-2001). Systemic
      concentrations of adiponectin and a wide range of anthropometric, metabolic, and
      inflammatory variables were available for analyses. The association of
      adiponectin with 15 immunological markers, including leukocyte count, acute-phase
      proteins, cytokines, cytokine receptors, and chemokines, was assessed using
      univariable and multivariable models. RESULTS: No evidence for a significant
      correlation between adiponectin and all immunological parameters except eotaxin
      could be found after multivariable adjustments, whereas multiple strong
      correlations with obesity and metabolic factors were present. CONCLUSIONS: From
      these data, we conclude that hypoadiponectinemia and a proinflammatory state are
      largely independent from each other.

PMID- 16801590
TI  - Short stature and the risk of adiposity, insulin resistance, and type 2 diabetes
      in middle age: the Third National Health and Nutrition Examination Survey (NHANES
      III), 1988-1994.
AB  - OBJECTIVE: To investigate the association between stature-related measurements
      (height, leg length, and leg length-to-height ratio) and adiposity, insulin
      resistance, and glucose intolerance. RESEARCH DESIGN AND METHODS: We conducted a
      cross-sectional analysis of a nationally representative sample of 7,424 adults
      aged 40-74 years, from the Third National Health and Nutrition Examination Survey
      (1988-1994). The main outcome measures were percent body fat, homeostasis model
      assessment of insulin resistance (HOMA-IR), and glucose intolerance based on the
      World Health Organization's 1985 criteria for an oral glucose tolerance test.
      RESULTS: Shorter height and leg length, and lower leg length-to-height ratio,
      were associated with higher percent body fat, especially in women. Lower leg
      length-to-height ratio was associated with greater insulin resistance estimated
      by HOMA-IR. In multinomial regression models adjusting for potential confounders,
      including percent body fat, the relative prevalence of type 2 diabetes per 1-SD
      lower values in height, leg length, and leg length-to-height ratio were 1.10 (95%
      CI 0.94-0.29), 1.17 (0.98-1.39), and 1.19 (1.02-1.39), respectively. CONCLUSIONS:
      Our study supports the hypothesis that adult markers of prepubertal growth,
      especially leg length-to-height ratio, are associated with adiposity, insulin
      resistance, and type 2 diabetes in the general U.S. population.

PMID- 16801592
TI  - Hypoadiponectinemia is associated with progression toward type 2 diabetes and
      genetic variation in the ADIPOQ gene promoter.
AB  - OBJECTIVE: Adiponectin encoded by the ADIPOQ gene modulates insulin sensitivity
      and glucose homeostasis. The aim of the current study was to investigate whether
      ADIPOQ gene variants in the promoter region predict adiponectin levels and type 2
      diabetes progression. RESEARCH DESIGN AND METHODS: A total of 550 subjects with
      increased risk of type 2 diabetes were investigated; they underwent a 75-g oral
      glucose tolerance test, repeated after 3 years. Adiponectin levels were analyzed,
      and two ADIPOQ promoter variant single nucleotide polymorphisms, -11391G>A and 
      11377C>G, were genotyped. RESULTS: Tertiles of the adjusted adiponectin levels
      were associated with single nucleotide polymorphism -11391G>A and -11377C>G
      haplotypes (P < 0.0001). Carriers of the intermediate/high-level haplotype
      combination showed a bisected diabetes risk at the 3-year follow-up and were
      characterized by a "regression" of glucose tolerance. Evolution of disease status
      correlates with preexisting low adiponectin levels at inclusion rather than with
      variation in adiponectin levels. CONCLUSIONS: We present data that gene variants
      in the ADIPOQ promoter region are associated with variations in adiponectin
      levels and thus with future type 2 diabetes and disease progression.

PMID- 16801591
TI  - A strong dose-response relation between serum concentrations of persistent
      organic pollutants and diabetes: results from the National Health and Examination
      Survey 1999-2002.
AB  - OBJECTIVE: Low-level exposure to some persistent organic pollutants (POPs) has
      recently become a focus because of their possible link with the risk of diabetes.
      RESEARCH DESIGN AND METHODS: Cross-sectional associations of the serum
      concentrations of POPs with diabetes prevalence were investigated in 2,016 adult
      participants in the National Health and Nutrition Examination Survey 1999-2002.
      Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p
      dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'
      dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they
      were detectable in >or=80% of participants. RESULTS: Compared with subjects with
      serum concentrations below the limit of detection, after adjustment for age, sex,
      race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes
      prevalence was strongly positively associated with lipid-adjusted serum
      concentrations of all six POPs. When the participants were classified according
      to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0,
      14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent
      in stratified analyses and stronger in younger participants, Mexican Americans,
      and obese individuals. CONCLUSIONS: There were striking dose-response relations
      between serum concentrations of six selected POPs and the prevalence of diabetes.
      The strong graded association could offer a compelling challenge to future
      epidemiologic and toxicological research.

PMID- 16801593
TI  - Increased adiposity at diagnosis in younger children with type 1 diabetes does
      not persist.

PMID- 16801594
TI  - Walking faster: distilling a complex prescription for type 2 diabetes management
      through pedometry.

PMID- 16801595
TI  - Should group education classes be separated by type of diabetes?

PMID- 16801596
TI  - The relationship between diabetes and infectious hospitalizations in renal
      transplant recipients.

PMID- 16801597
TI  - Lipoprotein(a) as a predictor of cardiovascular disease in a prospectively
      followed cohort of patients with type 1 diabetes.

PMID- 16801598
TI  - Elevated serum osteoprotegerin levels are associated with vascular endothelial
      dysfunction in type 2 diabetes.

PMID- 16801599
TI  - Absence of sexual dimorphism in the symptomatic responses to hypoglycemia in
      adults with and without type 1 diabetes.

PMID- 16801600
TI  - Kidney graft and patient survival with and without a simultaneous pancreas
      utilizing contralateral kidneys from the same donor.

PMID- 16801601
TI  - Risk associated with the metabolic syndrome versus the sum of its individual
      components.

PMID- 16801602
TI  - A systematic review of interventions to improve diabetes care in socially
      disadvantaged populations.
AB  - OBJECTIVE: To identify and synthesize evidence about the effectiveness of
      patient, provider, and health system interventions to improve diabetes care among
      socially disadvantaged populations. RESEARCH DESIGN AND METHODS: Studies that
      were included targeted interventions toward socially disadvantaged adults with
      type 1 or type 2 diabetes; were conducted in industrialized countries; were
      measured outcomes of self-management, provider management, or clinical outcomes;
      and were randomized controlled trials, controlled trials, or before-and-after
      studies with a contemporaneous control group. Seven databases were searched for
      articles published in any language between January 1986 and December 2004. Twenty
      six intervention features were identified and analyzed in terms of their
      association with successful or unsuccessful interventions. RESULTS: Eleven of 17
      studies that met inclusion criteria had positive results. Features that appeared
      to have the most consistent positive effects included cultural tailoring of the
      intervention, community educators or lay people leading the intervention, one-on
      one interventions with individualized assessment and reassessment, incorporating
      treatment algorithms, focusing on behavior-related tasks, providing feedback, and
      high-intensity interventions (>10 contact times) delivered over a long duration
      (>or=6 months). Interventions that were consistently associated with the largest
      negative outcomes included those that used mainly didactic teaching or that
      focused only on diabetes knowledge. CONCLUSIONS: This systematic review provides
      evidence for the effectiveness of interventions to improve diabetes care among
      socially disadvantaged populations and identifies key intervention features that
      may predict success. These types of interventions would require additional
      resources for needs assessment, leader training, community and family outreach,
      and follow-up.

PMID- 16801605
TI  - Preventing cardiovascular disease and diabetes: a call to action from the
      American Diabetes Association and the American Heart Association.

PMID- 16801603
TI  - Does the metabolic syndrome exist?

PMID- 16801606
TI  - Third Annual World Congress on the Insulin Resistance Syndrome: mediators,
      antecedents, and measurement.

PMID- 16801607
TI  - Glucose variability and complications.

PMID- 16801608
TI  - Possible problem with Optipen Pro-1: should diabetic patients continue to use
      this product?

PMID- 16801609
TI  - Implantable pump therapy restores metabolic control and quality of life in type 1
      diabetic patients with Buschke's nonsystemic scleroderma.

PMID- 16801610
TI  - Insulin allergy and immunologic insulin resistance caused by interleukin-6 in a
      patient with lung cancer.

PMID- 16801611
TI  - Improvement of type 2 diabetes in a lung cancer patient treated with Erlotinib.

PMID- 16801612
TI  - Relapse of diabetes after interruption of chronic administration of anti-tumor
      necrosis factor-alpha antibody infliximab: a case observation.

PMID- 16801613
TI  - Gestational diabetes mellitus in Sardinia: results from an early, universal
      screening procedure.

PMID- 16801614
TI  - An epidemiologic study on the prevalence of diabetes, glucose intolerance, and
      metabolic syndrome in the adult population of the Republic of Cyprus.

PMID- 16801615
TI  - Areca nut chewing is associated with metabolic syndrome: role of tumor necrosis
      factor-alpha, leptin, and white blood cell count in betel nut chewing-related
      metabolic derangements.

PMID- 16801616
TI  - The metabolic syndrome and glucose tolerance status deterioration over 23-year
      follow-up.

PMID- 16801617
TI  - A Rare but serious side effect of Levofloxacin: hypoglycemia in a geriatric
      patient.

PMID- 16801618
TI  - The prevalence and management of diabetes in rural India.

PMID- 16801619
TI  - Cigarette smoking affects urinary liver-type fatty acid-binding protein
      concentration in patients with early diabetic nephropathy.

PMID- 16801620
TI  - Validity of glycemic index estimates in the Insulin Resistance Atherosclerosis
      Study: response to Liese et al.

PMID- 16801621
TI  - A single factor underlies the metabolic syndrome: a confirmatory factor analysis:
      response to Pladevall et al.

PMID- 16801625
TI  - The health care response to pandemic influenza.
AB  - The threat of an H5N1 influenza virus (avian flu) pandemic is substantial. The
      success of the current U.S. influenza pandemic response plan depends on effective
      coordination among state and local public health authorities and individual
      health care providers. This article is a summary of a public policy paper
      developed by the American College of Physicians to address issues in the U.S.
      Department of Health and Human Services Pandemic Influenza Plan that involve
      physicians. The College's positions call for the following: 1) development of
      local public health task forces that include physicians representing all
      specialties and practice settings; 2) physician access to 2-way communication
      with public health authorities and to information technology tools for diagnosis
      and syndrome surveillance; 3) clear identification and authorization of agencies
      to process licensing and registration of volunteer physicians; 4) clear
      guidelines for overriding standard procedures for confidentiality and consent in
      the interest of the public's health; 5) clear and fair infection control measures
      that do not create barriers to care; 6) analysis of and solutions to current
      problems with seasonal influenza vaccination programs as a way of developing a
      maximally efficient pandemic flu vaccine program; 7) federal funding to provide
      pandemic flu vaccine for the entire U.S. population and antiviral drugs for 25%
      of the population; and 8) planning for health care in alternative, nonhospital
      settings to prevent a surge in demand for hospital care that exceeds supply.
      *This paper is an abridged version of a full-text position paper (available at
      http://www.acponline.org/college/pressroom/as06/pandemic_policy.pdf) written by
      Laura Barnitz, BJ, MA, and updated and adapted for publication in Annals of
      Internal Medicine by Michael Berkwits, MD, MSCE. The original position paper was
      developed for the Health and Public Policy Committee of the American College of
      Physicians: Jeffrey P. Harris, MD (Chair); David L. Bronson, MD (Vice Chair); CPT
      Julie Ake, MD; Patricia P. Barry, MD; Molly Cooke, MD; Herbert S. Diamond, MD;
      Joel S. Levine, MD; Mark E. Mayer, MD; Thomas McGinn, MD; Robert M. McLean, MD;
      Ashley E. Starkweather; and Frederick E. Turton, MD. It was approved by the Board
      of Regents on 3 April 2006.

PMID- 16801626
TI  - Influenza in 1918: recollections of the epidemic in Philadelphia. 1976.
AB  - When the great influenza epidemic struck Philadelphia in 1918, the author was
      just starting his third year at the University of Pennsylvania School of
      Medicine. After a single lecture on influenza, classes for the third and fourth
      year students were suspended while he and his mates manned an emergency hospital,
      in which they worked under little or no medical supervision and in the presence
      of an alarming patient mortality. This essay describes what happened in the
      hospital, and in the city as a whole, during the pandemic. Certain features of
      the clinical course of most patients permit the hope that modern therapy will
      prevent a repetition of the horrendous mortality.

PMID- 16801627
TI  - Planning for avian influenza.
AB  - Avian influenza, or influenza A (H5N1), has 3 of the 4 properties necessary to
      cause a serious pandemic: It can infect people, nearly all people are
      immunologically naive, and it is highly lethal. The Achilles heel of the virus is
      the lack of sustained human-human transmission. Fortunately, among the 124 cases
      reported through 30 May 2006, nearly all were acquired by direct contact with
      poultry. Unfortunately, the capability for efficient human-human transmission
      requires only a single mutation by a virus that is notoriously genetically
      unstable, hence the need for a new vaccine each year for seasonal influenza.
      Influenza A (H5N1) is being compared to another avian strain, the agent of the
      "Spanish flu" of 1918-1919, which traversed the world in 3 months and caused an
      estimated 50 million deaths. The question is, are we ready for this type of
      pandemic? The answer is probably no. The main problems are the lack of an
      effective vaccine, very poor surge capacity, a health care system that could not
      accommodate even a modest pandemic, and erratic regional planning. It's time to
      get ready, and in the process be ready for bioterrorism, natural disasters, and
      epidemics of other infectious diseases.

PMID- 16801628
TI  - Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in
      situ: ten-year results of European Organisation for Research and Treatment of
      Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer
      Cooperative Group and EORTC Radiotherapy Group.
AB  - PURPOSE: The European Organisation for Research and Treatment of Cancer conducted
      a randomized trial investigating the role of radiotherapy (RT) after local
      excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the
      efficacy of RT with 10 years follow-up on both the overall risk of local
      recurrence (LR) and related to clinical, histologic, and treatment factors.
      PATIENTS AND METHODS: After complete LE, women with DCIS were randomly assigned
      to no further treatment or RT (50 Gy). One thousand ten women with mostly (71%)
      mammographically detected DCIS were included. The median follow-up was 10.5
      years. RESULTS: The 10-year LR-free rate was 74% in the group treated with LE
      alone compared with 85% in the women treated by LE plus RT (log-rank P < .0001;
      hazard ratio [HR] = 0.53). The risk of DCIS and invasive LR was reduced by 48% (P
      = .0011) and 42% (P = .0065) respectively. Both groups had similar low risks of
      metastases and death. At multivariate analysis, factors significantly associated
      with an increased LR risk were young age (< or = 40 years; HR = 1.89),
      symptomatic detection (HR = 1.55), intermediately or poorly differentiated DCIS
      (as opposed to well-differentiated DCIS; HR = 1.85 and HR = 1.61 respectively),
      cribriform or solid growth pattern (as opposed to clinging/micropapillary
      subtypes; HR = 2.39 and HR = 2.25 respectively), doubtful margins (HR = 1.84),
      and treatment by LE alone (HR = 1.82). The effect of RT was homogeneous across
      all assessed risk factors. CONCLUSION: With long-term follow-up, RT after LE for
      DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years. All
      patient subgroups benefited from RT.

PMID- 16801629
TI  - The case for individualized screening recommendations for breast cancer.

PMID- 16801630
TI  - Overcoming resistance to interferon-induced apoptosis of renal carcinoma and
      melanoma cells by DNA demethylation.
AB  - Epigenetic editing of gene expression by aberrant methylation of DNA may help
      tumor cells escape attack from the innate and acquired immune systems. Resistance
      to antiproliferative effects and apoptosis induction by interferons (IFNs) was
      postulated to result from silencing of IFN response genes by promoter
      hypermethylation. Treatment of human ACHN renal cell carcinoma (RCC) and A375
      melanoma cells with the DNA demethylating nucleoside analog 5-AZA-2'
      deoxycytidine (5-AZA-dC) synergistically augmented antiproliferative effects of
      IFN- alpha (alpha) 2 and IFN-beta (beta). Either 5-AZA-dC or an antisense to DNA
      methyltransferase 1 (DNMT1) overcame resistance to apoptosis induction by IFNs
      with up to 85% apoptotic cells resulting from the combinations. No similar
      potentiation occurred in normal kidney epithelial cells. IFN response genes were
      augmented more than 10 times in expression by 5-AZA-dC. Demethylation by 5-AZA-dC
      of the promoter of the prototypic, apoptosis-associated IFN response gene XAF1
      was confirmed by methylation-specific polymerase chain reaction. siRNA to XAF1
      inhibited IFN-induced apoptosis; conversely, overexpression of XAF1 overcame
      resistance to apoptosis induction by IFN-beta. As occurred with apoptosis
      resistant melanoma cells in vitro, tumor growth inhibition in the nude mouse of
      human A375 melanoma xenografts resulted from treatment with 5-AZA-dC in
      combination with IFN-beta, an effect not resulting from either single agent. The
      importance of epigenetic remodeling of expression of immune-modifying genes in
      tumor cells was further suggested by identifying reactivation of the cancer
      testis antigens MAGE and RAGE in ACHN cells after DNMT1 depletion. Thus,
      inhibitors of DNMT1 may have clinical relevance for immune modulation by
      augmentation of cytokine effects and/or expression of tumor-associated antigens.

PMID- 16801631
TI  - Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation
      carriers in the international BRCA1/2 carrier cohort study: a report from the
      EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators' Group.
AB  - PURPOSE: Women who carry germline mutations in the BRCA1 and BRCA2 genes are at
      greatly increased risk of breast cancer (BC). Numerous studies have shown that
      moderate to high doses of ionizing radiation are a risk factor for BC. Because of
      the role of the BRCA proteins in DNA repair, we hypothesized that BRCA carriers
      might be more sensitive to ionizing radiation than women in the general
      population. PATIENTS AND METHODS: A retrospective cohort study of 1,601 female
      BRCA1/2 carriers was performed. Risk of breast cancer from exposure to chest x
      rays, as assessed by questionnaire data, was analyzed using a weighted Cox
      proportional hazards model. RESULTS: In this cohort, any reported exposure to
      chest x-rays was associated with an increased risk of BC (hazard ratio [HR] =
      1.54; P = .007). This risk was increased in carrier women aged 40 years and
      younger (HR = 1.97; P < .001) and in women born after 1949 (HR = 2.56; P < .001),
      particularly those exposed only before the age of 20 years (HR = 4.64; P < .001).
      CONCLUSION: In our series of BRCA carriers, we detected a relatively large effect
      on BC risk with a level of radiation exposure that is at least an order of
      magnitude lower than in previously studied medical radiation-exposed cohorts.
      Although part of this increase may be attributable to recall bias, the observed
      patterns of risk in terms of age at exposure and attained age are consistent with
      those found in previous studies. If confirmed, the results have important
      implications for the use of x-ray imaging in young BRCA1/2 carriers.

PMID- 16801632
TI  - The influence of race and gender on time to initial electrocardiogram for
      patients with chest pain.
AB  - OBJECTIVES: To determine whether race or gender affected time to initial
      electrocardiogram (ECG) for patients who presented to an emergency department
      with chest pain. METHODS: This was a prospective cohort study of patients with
      chest pain. Patients were divided into three groups based on final diagnosis of
      acute myocardial infarction or unstable angina and all others with noncardiac
      chest pain. Data were analyzed using ranks in a two-way analysis of covariance
      adjusted for age. RESULTS: A total of 4,358 patients were studied; 58.6% were
      women and 41.4% men, and 70.3% were African American, 26.0% white, and 3.6%
      other. Overall, nonwhite patients had longer times to initial ECG compared with
      white patients. These effects were consistent regardless of ultimate diagnosis.
      Overall, women had longer times to initial ECG than men. However, ECG time
      differed by final diagnosis. There were no differences in time to ECG for women
      compared with men with acute myocardial infarction or unstable angina, but women
      received an ECG significantly slower than men for noncardiac chest pain.
      CONCLUSIONS: The first screening test for acute coronary syndrome, the ECG, took
      longer to obtain for nonwhite patients, regardless of final diagnosis. This was
      unfortunately consistent with the literature that shows racial disparities in all
      aspects of emergent cardiac care. For women, the overall delay in ECG time can be
      explained by delays for those women with noncardiac chest pain.

PMID- 16801633
TI  - Equipment, supplies, and pharmaceuticals: how much might it cost to achieve basic
      surge capacity?
AB  - The ability to deliver optimal medical care in the setting of a disaster event,
      regardless of its cause, will in large part be contingent on an immediately
      available supply of key medical equipment, supplies, and pharmaceuticals.
      Although the Department of Health and Human Services Strategic National Stockpile
      program makes these available through its 12-hour "push packs" and vendor-managed
      inventory, every local community should be funded to create a local cache for
      these items. This report explores the funding requirements for this suggested
      approach. Furthermore, the response to a surge in demand for care will be
      contingent on keeping available staff close to the hospitals for a sustained
      period. A proposal for accomplishing this, with associated costs, is discussed as
      well.

PMID- 16801634
TI  - Safety testing of automated external defibrillators with humans in
      electromagnetic fields and relevance for public access defibrillation.

PMID- 16801635
TI  - Theory and reality for software patents: good in concept, not so good in
      practice.

PMID- 16801636
TI  - Patient page. Chronic migraine and medication-overuse headache.

PMID- 16801637
TI  - Clinical findings of the phakomatoses: hypomelanosis of Ito.

PMID- 16801638
TI  - STN DBS in PD: selection criteria for surgery should include cognitive and
      psychiatric factors.

PMID- 16801639
TI  - Alzheimer neuropathology in nondemented aging: keeping mind over matter.

PMID- 16801640
TI  - Perforator stroke following intracranial stenting: a sacrifice for the greater
      good?

PMID- 16801641
TI  - Practice Advisory: utility of surgical decompression for treatment of diabetic
      neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of
      the American Academy of Neurology.
AB  - Surgical decompression at the site of anatomic narrowing has been promoted as an
      alternative treatment for patients with symptomatic diabetic neuropathy.
      Systematic review of the literature revealed only Class IV studies concerning the
      utility of this therapeutic approach. Given the current evidence available, this
      treatment alternative should be considered unproven (Level U). Prospective
      randomized controlled trials with standard definitions and outcome measures are
      necessary to determine the value of this therapeutic intervention.

PMID- 16801642
TI  - Neurosurgery in Parkinson disease: a distressed mind in a repaired body?
AB  - OBJECTIVE: To prospectively evaluate the impact of subthalamic nucleus (STN)
      stimulation on social adjustment in patients with Parkinson disease (PD).
      METHODS: Before and 18 to 24 months after bilateral STN stimulation, the authors
      assessed 29 patients with PD for motor disability, cognition (Mattis dementia
      rating scale, frontal score), psychiatric morbidity (Mini-5.0.0, MADRS, BAS),
      quality of life (PDQ-39), social adjustment (Social Adjustment Scale), and
      psychological status using unstructured in-depth interviews. RESULTS: Despite
      marked improvement in parkinsonian motor disability, the absence of significant
      changes in cognitive status, and improvement of activities of daily living and
      quality of life by the end of the study, social adjustment did not improve.
      Several kinds of problems with social adjustment were observed, affecting the
      patients' perception of themselves and their body, marital situation, and
      professional life. Marital conflicts occurred in 17/24 couples. Only 9 out of 16
      patients who had a professional activity before the operation went back to work
      after surgery. CONCLUSION: After STN stimulation, patients experienced
      difficulties in their relations with themselves, their spouses, their families,
      and their socio-professional environment. The authors suggest a multidisciplinary
      psychosocial preparation and follow-up to help patients and their entourage cope
      with the sudden changes in their existence following successful neurosurgery.

PMID- 16801643
TI  - The thalamus and behavior: effects of anatomically distinct strokes.
AB  - Data on behavioral changes after thalamic lesion are sparse and largely based on
      isolated reports of patients with thalamic strokes. However, recent findings
      suggest that behavioral patterns can be delineated on the basis of the four main
      arterial thalamic territories. The anterior pattern consists mainly of
      perseverations and superimposition of unrelated information, apathy, and amnesia.
      After paramedian infarct, the most frequent features are disinhibition syndromes,
      with personality changes, loss of self-activation, amnesia, and, in the case of
      extensive lesions, thalamic "dementia"; this pattern may often be difficult to
      distinguish from primary psychiatric disorders, especially when neurologic
      dysfunction is lacking. After inferolateral lesion, executive dysfunction may
      develop but is often overlooked, although it may occasionally lead to severe long
      term disability. After posterior lesion, whereas cognitive dysfunction with
      neglect and aphasia are well known, no specific behavioral syndrome has been
      reported. In the future, perfusion CT, functional MRI, and tractography using
      diffusion imaging in stroke patients may provide a better understanding of the
      role of the corticothalamic relationship in behavioral changes associated with
      thalamic stroke.

PMID- 16801644
TI  - Helicobacter pylori eradication and l-dopa absorption in patients with PD and
      motor fluctuations.
AB  - OBJECTIVE: To investigate if Helicobacter pylori (HP) eradication could make an
      effective and long-lasting improvement in the pharmacokinetic and clinical
      response to l-dopa in patients with Parkinson disease (PD) and motor
      fluctuations. METHODS: In a group of 34 HP-infected, motor-fluctuating patients
      with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP
      eradication (n = 17) was investigated in a double-blind fashion in comparison
      with a generic antioxidant treatment (n = 17), by means of pharmacokinetic,
      clinical, and gastrointestinal assessments. Results were compared with placebo
      treatment. RESULTS: Differently from the antioxidant-treated patients, the HP
      eradicated patients showed a significant increase of l-dopa absorption, which was
      coupled with a significant improvement of clinical disability and with a
      prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly
      decreased in line with a better l-dopa pharmacokinetics. CONCLUSIONS: These data
      demonstrate a reversible Helicobacter pylori (HP)-induced interference with l
      dopa clinical response related to the impaired drug absorption, probably due to
      active gastroduodenitis. Therefore, the authors suggest that HP eradication may
      improve the clinical status of infected patients with Parkinson disease and motor
      fluctuations by modifying l-dopa pharmacokinetics.

PMID- 16801645
TI  - Neuropsychological effects of bilateral STN stimulation in Parkinson disease: a
      controlled study.
AB  - OBJECTIVE: To evaluate the cognitive and behavioral effects of bilateral
      subthalamic nucleus (STN) stimulation in patients with Parkinson disease (PD).
      METHODS: The authors included 103 patients; 99 patients were evaluated 6 months
      after surgery. A control group of 39 patients with PD was formed and 36 patients
      were evaluated 6 months later. At baseline and at follow-up we administered
      neuropsychological tests of language, memory, visuospatial function, mental
      speed, and executive functions. A depression rating scale, a quality of life
      scale, self and proxy ratings of memory and dysexecutive symptoms, and a
      neuropsychiatric interview were also administered. RESULTS: Six months after
      surgery, the STN group showed a larger decline than the control group on measures
      of verbal fluency, color naming, selective attention, and verbal memory.
      Moreover, the STN group showed a decrease in positive affect, and an increase in
      emotional lability and cognitive complaints. On the other hand, the STN group
      showed an increase in quality of life and a slight decrease in depressive
      symptoms. Nine percent of the STN patients had psychiatric complications (vs 3%
      of controls). CONCLUSIONS: Bilateral subthalamic nucleus stimulation has an
      adverse effect on executive functions with implications for daily life of the
      patients and their relatives.

PMID- 16801646
TI  - Solitary pyogenic abscess of the medulla oblongata: survival after aspiration and
      antibiotics.

PMID- 16801648
TI  - Voxel-based detection of white matter abnormalities in mild Alzheimer disease.
AB  - OBJECTIVE: To detect white matter abnormalities in patients with mild Alzheimer
      disease (AD) by diffusion tensor imaging and to determine their topographic
      relationship with gray matter atrophy. METHODS: Thirteen patients with mild AD
      and 16 normal age-matched volunteers underwent diffusion tensor imaging and three
      dimensional spoiled gradient-recalled sequence scanning. Voxel-based morphometry
      was conducted to detect regions of gray matter atrophy in the AD group relative
      to the control group. Fractional anisotropy (FA) maps were processed using SPM2
      to make voxel-wise comparison of anisotropy in whole brain between the two
      groups. The relationship between locations of abnormalities in the white and gray
      matter was examined. RESULTS: Significant reductions in anisotropy were found in
      the white matter of both medial temporal lobes, bilateral temporal stems,
      bilateral superior longitudinal fasciculi, bilateral internal capsules, and
      cerebral peduncles, as well as the white matter of left middle temporal gyrus and
      right superior parietal lobule, the body and genu of the corpus callosum, and the
      right lateral capsule in patients with AD. Although the decrease in FA was
      consistent with cortical volumetric reduction in both temporal lobes, the
      widespread involvement of bilateral superior longitudinal fasciculi was dominant
      in these white matter findings. CONCLUSIONS: Voxel-wise comparison of whole-brain
      anisotropy revealed widely distributed disintegration of white matter in mild
      Alzheimer disease (AD). The white matter shows a different pattern of
      degeneration from gray matter and may be an independent factor in the progress of
      AD.

PMID- 16801647
TI  - Neuropathology of older persons without cognitive impairment from two community
      based studies.
AB  - OBJECTIVE: To examine the relation of National Institute on Aging-Reagan (NIA
      Reagan) neuropathologic criteria of Alzheimer disease (AD) to level of cognitive
      function in persons without dementia or mild cognitive impairment (MCI). METHODS:
      More than 2,000 persons without dementia participating in the Religious Orders
      Study or the Memory and Aging Project agreed to annual detailed clinical
      evaluation and brain donation. The studies had 19 neuropsychological performance
      tests in common that assessed five cognitive domains, including episodic memory,
      semantic memory, working memory, perceptual speed, and visuospatial ability. A
      total of 134 persons without cognitive impairment died and underwent brain
      autopsy and postmortem assessment for AD pathology using NIA-Reagan
      neuropathologic criteria for AD, cerebral infarctions, and Lewy bodies. Linear
      regression was used to examine the relation of AD pathology to level of cognitive
      function proximate to death. RESULTS: Two (1.5%) persons met NIA-Reagan criteria
      for high likelihood AD, and 48 (35.8%) met criteria for intermediate likelihood;
      29 (21.6%) had cerebral infarctions, and 18 (13.4%) had Lewy bodies. The mean
      Mini-Mental State Examination score proximate to death was 28.2 for those meeting
      high or intermediate likelihood AD by NIA-Reagan criteria and 28.4 for those not
      meeting criteria. In linear regression models adjusted for age, sex, and
      education, persons meeting criteria for intermediate or high likelihood AD scored
      about a quarter standard unit lower on tests of episodic memory (p = 0.01). There
      were no significant differences in any other cognitive domain. CONCLUSIONS:
      Alzheimer disease pathology can be found in the brains of older persons without
      dementia or mild cognitive impairment and is related to subtle changes in
      episodic memory.

PMID- 16801649
TI  - Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD.
AB  - OBJECTIVE: To evaluate the diagnostic reliability of cardiac iodine-123
      metaiodobenzylguanidine ((123)I-MIBG) radioactivity in discriminating dementia
      with Lewy bodies (DLB) from Alzheimer disease (AD) regardless of parkinsonism.
      BACKGROUND: The diagnosis of DLB may be confounded by the absence of
      parkinsonism. This highlights the need to improve the accuracy of antemortem
      diagnosis of DLB without parkinsonism. METHODS: Cardiac sympathetic denervation
      was examined using myocardial (123)I-MIBG scintigraphy in 37 patients with DLB,
      42 patients with AD, and 10 normal elderly controls. The DLB patients consisted
      of seven patients without parkinsonism (DLB/P-) and 30 patients with parkinsonism
      (DLB/P+) at the time of the study. RESULTS: The heart-to-mediastinum uptake ratio
      (H/M ratio) of myocardial MIBG uptake was decreased in both the DLB groups vs the
      AD group (p < 0.0001) and control group (p < 0.0001). The washout rate (WR) was
      higher in the DLB group than in the control group (p < 0.0001) and AD group (p <
      0.0001). No differences were found between the AD and control groups or between
      the DLB/P+ and DLB/P- groups in either the early or delayed H/M ratio or WR. In
      discriminating between DLB and AD, regardless of parkinsonism, the delayed H/M
      ratio had a sensitivity of 100%, a specificity of 100%, and a positive predictive
      value of 100% at a cutoff value of 1.68. CONCLUSIONS: Our results indicate that
      dementia with Lewy bodies results in cardiac sympathetic denervation and that
      iodine-123 metaiodobenzylguanidine myocardial scintigraphy is a sensitive tool
      for discriminating dementia with Lewy bodies from Alzheimer disease even in
      patients without parkinsonism.

PMID- 16801650
TI  - Degree of handedness and cerebral dominance.
AB  - OBJECTIVE: To examine the relationship between the degree of handedness and
      hemispheric language dominance in patients with epilepsy. METHODS: The authors
      examined the relationship between degree of handedness and hemispheric language
      dominance in 174 epilepsy surgery candidates using the intracarotid amobarbital
      procedure and results from a modified version of the Edinburgh Handedness
      Inventory. RESULTS: The incidence of atypical language dominance increased
      linearly with the degree of left-handedness, from 9% in strong right-handers
      (laterality quotient [LQ] = +100) to 46% in ambidextrous individuals and 69% in
      strong left-handers (LQ = -100). CONCLUSIONS: The incidence of atypical language
      dominance depends not only on the direction but also on the degree of handedness.
      In addition, direction of language dominance varies with hemisphere of seizure
      focus and degree of handedness. A familial history of sinistrality may have an
      additional effect on the likelihood of atypical dominance.

PMID- 16801651
TI  - Functional anatomy of the therapeutic effects of prism adaptation on left
      neglect.
AB  - OBJECTIVE: To investigate the anatomic substrates underlying the beneficial
      effect of prism adaptation in five patients with persistent left neglect
      following right stroke. METHODS: In a functional imaging PET study, we used a
      covariation analysis to examine linear changes of regional cerebral blood flow
      over sessions as a function of left neglect improvement. RESULTS: The network of
      significant brain regions associated with improvement of left neglect performance
      produced by prism adaptation involved the right cerebellum, the left thalamus,
      the left temporo-occipital cortex, the left medial temporal cortex, and the right
      posterior parietal cortex. CONCLUSION: Our results suggest that the realignment
      of visuomotor coordinates is processed by the cerebellum and that low level
      sensorimotor adaptation actively modulates cerebral areas, albeit now relying on
      intact cerebellocerebral connections. Hence, our data support the hypothesis that
      the beneficial effect of prism adaptation on the clinical presentation of left
      neglect derives from modulation of cortical regions implicated in spatial
      cognition.

PMID- 16801653
TI  - Detection of intracranial venous reflux in patients of transient global amnesia.
AB  - BACKGROUND: The mechanism of transient global amnesia (TGA) is not clear.
      Attempting to support the hypothesis that retrograde venous hypertension causing
      cerebral venous ischemia plays a role in the pathogenesis of TGA, the authors
      used cranial three-dimensional time-of-flight (TOF) MR angiography (MRA) to
      detect a possible intracranial retrograde venous flow in TGA patients. METHODS:
      The frequency of abnormal venous signals on cranial three-dimensional TOF MRA was
      compared in 10 TGA patients with the signals in 50 age- and gender-matched normal
      individuals. In TGA patients with abnormal venous signals, other examinations
      (cerebral digital subtraction angiography, upper extremity digital subtraction
      venography [DSV], and thoracic inlet MRI) were performed to elucidate the
      etiology of these abnormal intracranial venous flow patterns. RESULTS: Abnormal
      venous signals on three-dimensional TOF MRA were found in five (50%) of the TGA
      patients and none of the control subjects (p < 0.001). Compression leading to
      occlusion of the left brachiocephalic vein by the sternum and aorta during
      regular breathing, as depicted by upper extremity DSV and thoracic inlet MRI,
      occurred consistently among these five TGA patients with abnormal venous signals.
      CONCLUSIONS: Retrograde intracranial venous flow caused by left brachiocephalic
      vein occlusion was found only in patients with transient global amnesia (TGA).
      This result suggests that TGA patients may have an underlying impairment of
      cerebral venous outflow that increases their vulnerability to TGA attack.

PMID- 16801652
TI  - Perforator stroke after elective stenting of symptomatic intracranial stenosis.
AB  - OBJECTIVE: To study the frequency, clinical course, and functional outcome of
      perforator stroke (PS) resulting from elective stenting of symptomatic
      intracranial stenosis. METHODS: Between September 2001 and November 2004, 169
      consecutive patients with 181 symptomatic intracranial stenoses underwent
      stenting procedure at our institute. The preoperative perforator infarct adjacent
      to the stenotic segment (PIAS) on MRI was evaluated blindly. Patients who
      developed PS after stenting were enrolled. Each patient was assessed by an
      experienced stroke neurologist by neurologic examination and NIH Stroke Scale
      score every day until discharge and at day 30, and by modified Rankin Scale (mRS)
      score at the end of the first, third, and sixth month, and then at intervals of 6
      months. RESULTS: PS frequency was 3.0% (5/169 patients). The patients with
      preoperative PIAS had a higher frequency of PS and PS exacerbation, resulting
      from intracranial stenting (8.2%, 4/49), vs patients without preoperative PIAS
      (0.8%, 1/120; p = 0.031). Four PSs occurred during the procedure and one 10 hours
      after stenting. Four PSs reached the maximum deficit almost at once, and one
      after 2 hours from onset. All five patients were functionally independent (mRS
      <or= 1) within 12 months. CONCLUSION: Patients with preoperative perforator
      infarct adjacent to the stenotic segment have a higher perforator stroke
      frequency after elective stenting of intracranial stenosis. Most perforator
      strokes occur during the procedure and reach the maximum deficit almost
      immediately. Functional outcomes are relatively good.

PMID- 16801654
TI  - Impact of acute blood pressure variability on ischemic stroke outcome.
AB  - BACKGROUND: The authors previously reported a low initial emergency department
      (ED) blood pressure (BP) to be associated with a significantly increased risk of
      death at 90 days. In this article, they examine the impact of acute BP
      variability following onset of ischemic stroke. METHODS: The study cohort
      consisted of 71 patients with stroke onset less than 24 hours. BP measurements
      were obtained every 5 minutes for the duration of the patient's ED stay. During
      the first 180 minutes, the median number of readings per patient was 9 (range 2
      to 30). RESULTS: The baseline median systolic (sBP) and diastolic (dBP) BPs were
      not different for the patients that died within 90 days compared with those that
      were alive (p = 0.91 for sBP and p = 0.27 for dBP). Patients who died within 90
      days had a greater differential in their dBP during the first 180 minutes than
      the patients that were alive after 90 days (median 44.5 vs 25 mm Hg; Wilcoxon
      rank sum test, p < 0.001). A similar result was observed for sBP (median 47 vs 30
      mm Hg; p = 0.047). CONCLUSION: Wide fluctuation of blood pressure in the first 3
      hours of the emergency department stay in patients with acute ischemic stroke
      appears to be associated with an increased risk of death at 90 days.

PMID- 16801655
TI  - Patient-perceived impact of resective epilepsy surgery.
AB  - OBJECTIVE: To evaluate the patient-perceived impact of resective epilepsy
      surgery, a key outcome to consider in evaluating such a highly invasive, elective
      procedure. METHODS: Impact measures obtained from 396 patients in a multicenter
      cohort study of resective epilepsy surgery included (1) willingness to undergo
      surgery if that decision could be made again and (2) the overall impact of
      surgery on the patient's life. Predictors of impact were analyzed using
      multivariate ordinal logistic regression. RESULTS: Of study participants, 73.8%,
      77.4%, and 75.5% would definitely undergo surgery again and 78.2%, 80.2%, and
      79.1% reported a very strong or strong positive overall impact of surgery at 3,
      12, and 24 months. Multivariate ordinal logistic regression showed that seizure
      freedom predicted more positive perceptions at 3, 12, and 24 months (all p <
      0.04). Becoming employed was uniquely associated with willingness to undergo
      surgery again and with overall impact at 24 months (all p < 0.05), but only a net
      7% of the cohort improved their employment status. Right-sided resection (at 12
      and 24 months, p < 0.005) and female gender (at 3 and 12 months, p = 0.006) were
      each positively associated with perceived overall impact. CONCLUSIONS: Most
      epilepsy surgery patients report a positive overall impact of the procedure on
      their lives and a high willingness to undergo surgery again if that choice could
      be made. Seizure-free individuals express consistently more positive perceptions
      of the procedure. Findings suggest that it is important to make early efforts to
      reintegrate epilepsy surgery patients into employment.

PMID- 16801656
TI  - A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster
      headache cohort.
AB  - OBJECTIVE: To investigate the molecular genetic basis of cluster headache (CH),
      using a genome-wide scan and candidate gene strategy. METHODS: Northern European
      CH families and a case-control cohort of Danish, Swedish, and British origin
      (total n = 259 sporadic CH patients), including 267 control subjects matched for
      ancestry, participated in the study. A genome-wide genetic screen using
      approximately 400 microsatellite markers was performed for five informative
      Danish CH families. Additional markers were typed for those loci generating
      statistical evidence suggestive of linkage, together with genotypes for 111
      individuals from further Danish and Italian kindreds. Sporadic CH patients and
      controls were investigated by association analysis for variation in the candidate
      gene, HCRTR2. Finally, complete HCRTR2 sequencing was undertaken for eight
      independent probands. RESULTS: Potential linkage was identified at four possible
      disease loci in Danish kindreds, yet no single chromosome location generated a
      lod or NPL score of recognized significance. No deleterious sequence variants of
      the HCRTR2 gene were detected by comparison to wild-type sequence. Association of
      the HCRTR2 gene was not replicated in this large dataset, even when the data were
      stratified into distinct populations. CONCLUSIONS: Cluster headache is a complex
      genetic disorder, with possible phenotypic and genetic heterogeneity compounding
      attempts at gene identification.

PMID- 16801657
TI  - Diagnostic performance of spectroscopic and perfusion MRI for distinction of
      brain tumors.
AB  - OBJECTIVE: To assess the value of spectroscopic and perfusion MRI for glioma
      grading and for distinguishing glioblastomas from metastases and from CNS
      lymphomas. METHODS: The authors examined 79 consecutive patients with first
      detection of a brain neoplasm on nonenhanced CT scans and no therapy prior to
      evaluation. Spectroscopic MRI; arterial spin-labeling MRI for measuring cerebral
      blood flow (CBF); first-pass dynamic, susceptibility-weighted, contrast-enhanced
      MRI for measuring cerebral blood volume; and T1-weighted dynamic contrast
      enhanced MRI were performed. Receiver operating characteristic analysis was
      performed, and optimum thresholds for tumor classification and glioma grading
      were determined. RESULTS: Perfusion MRI had a higher diagnostic performance than
      spectroscopic MRI. Because of a significantly higher tumor blood flow in
      glioblastomas compared with CNS lymphomas, a threshold value of 1.2 for CBF
      provided sensitivity of 97%, specificity of 80%, positive predictive value (PPV)
      of 94%, and negative predictive value (NPV) of 89%. Because CBF was significantly
      higher in peritumoral nonenhancing T2-hyperintense regions of glioblastomas
      compared with metastases, a threshold value of 0.5 for CBF provided sensitivity,
      specificity, PPV, and NPV of 100%, 71%, 94%, and 100%. Glioblastomas had the
      highest tumor blood flow values among all other glioma grades. For discrimination
      of glioblastomas from grade 3 gliomas, sensitivity was 97%, specificity was 50%,
      PPV was 84%, and NPV was 86% (CBF threshold value of 1.4), and for discrimination
      of glioblastomas from grade 2 gliomas, sensitivity was 94%, specificity was 78%,
      PPV was 94%, and NPV was 78% (CBF threshold value of 1.6). CONCLUSION: Perfusion
      MRI is predictive in distinguishing glioblastomas from metastases, CNS lymphomas
      and other gliomas vs MRI and magnetic resonance spectroscopy.

PMID- 16801658
TI  - The localization of facial motor impairment in sporadic Mobius syndrome.
AB  - OBJECTIVE: To investigate the neurophysiologic aspects of facial motor control in
      patients with sporadic Mobius syndrome defined as nonprogressive congenital
      facial and abducens palsy. METHODS: The authors assessed 24 patients with
      sporadic Mobius syndrome by performing a complete clinical examination and
      neurophysiologic tests including facial nerve conduction studies, needle
      electromyography examination of facial muscles, and recording of the blink reflex
      and of the trigeminofacial inhibitory reflex. RESULTS: Two distinct groups of
      patients were identified according to neurophysiologic testing. The first group
      was characterized by increased facial distal motor latencies (DMLs) and poor
      recruitment of small and polyphasic motor unit action potentials (MUAPs). The
      second group was characterized by normal facial DMLs and neuropathic MUAPs. It is
      hypothesized that in the first group, the disorder is due to a rhombencephalic
      maldevelopment with selective sparing of small-size MUs, and in the second group,
      the disorder is related to an acquired nervous injury during intrauterine life,
      with subsequent neurogenic remodeling of MUs. The trigeminofacial reflexes showed
      that in most subjects of both groups, the functional impairment of facial
      movements was caused by a nuclear or peripheral site of lesion, with little
      evidence of brainstem interneuronal involvement. CONCLUSION: Two different
      neurophysiologically defined phenotypes can be distinguished in sporadic Mobius
      syndrome, with different pathogenetic implications.

PMID- 16801659
TI  - Erasmus Darwin (1731-1802): neurologist.
AB  - Erasmus Darwin was the founder of evolutionary biology, a renown poet, an
      inventor, and a general medical practitioner. Erasmus Darwin wrote specifically
      about the evolutionary and phylogenetic development of the nervous system,
      neuroembryology, psychiatric illness (including delusions and depression), and
      electrical therapy for childhood hemiplegia. He conducted experiments in neuro
      ophthalmology and wrote about color vision, afterimages, the blind spot, and
      visual memory.

PMID- 16801660
TI  - Response of cluster headache to psilocybin and LSD.
AB  - The authors interviewed 53 cluster headache patients who had used psilocybin or
      lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26
      psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin
      users and 7 of 8 LSD users reported cluster period termination; 18 of 19
      psilocybin users and 4 of 5 LSD users reported remission period extension.
      Research on the effects of psilocybin and LSD on cluster headache may be
      warranted.

PMID- 16801661
TI  - Multifocal axonal polyneuropathy in celiac disease.
AB  - The authors report six patients with multifocal axonal polyneuropathy and the
      subsequent diagnosis of celiac disease (CD). Five patients did not improve or had
      only modest improvement following dietary intervention or immune therapies; one
      patient with marked weakness and mild electrodiagnostic findings had complete
      resolution of the neuropathy following immunomodulatory therapy. CD may be a
      cause of multifocal axonal polyneuropathy.

PMID- 16801662
TI  - Dysphagia in facioscapulohumeral muscular dystrophy.
AB  - Dysphagia is not considered a symptom of facioscapulohumeral muscular dystrophy
      (FSHD). In this study, the authors found that dysphagia does occur in patients
      with advanced FSHD showing mild involvement of the jaw and lingual muscles.
      Dysphagia is seldom life threatening in these patients. The authors conclude that
      dysphagia should not be considered an exclusion criterion for FSHD.

PMID- 16801663
TI  - Possible gender-dependent association of vascular endothelial growth factor
      (VEGF) gene and ALS.
AB  - Individuals homozygous for haplotypes -2578-A/-1154-A/-634-G or -2578-A/-1154-G/
      634-G in the promoter/5'UTR of the VEGF gene have a 1.8-fold increased risk of
      ALS in several European populations. We did not observe any significant
      association with single markers, or haplotype pairs, in a German sample of 580
      sporadic ALS patients and 628 controls. However, the promoter SNP-1154
      (rs1570360) was associated with affection status in women (p = 0.036), suggesting
      that the VEGF effect may be dependent on the sex ratio of the sample.

PMID- 16801664
TI  - Mitochondrial disease in adults: a scale to monitor progression and treatment.
AB  - The natural history of mitochondrial diseases is poorly understood, limiting our
      ability to offer prognostic advice to patients or to evaluate therapy. One major
      obstacle to improving our understanding is the lack of a clinical rating scale to
      monitor the extensive clinical spectrum of mitochondrial disease. In this
      article, the authors describe the development and validation of a practical and
      semiquantitative rating scale, the Newcastle Mitochondrial Disease Adult Scale.

PMID- 16801665
TI  - Brain atrophy after immunoablation and stem cell transplantation in multiple
      sclerosis.
AB  - The authors measured brain atrophy in nine patients undergoing immunoablation and
      autologous hematopoietic stem cell transplantation for multiple sclerosis. From
      baseline to 1 month after treatment, atrophy was 10 times faster than before
      treatment. A patient with non-CNS lymphoma showed comparable acute brain atrophy
      after analogous therapy. These observations suggest that brain atrophy after
      immunoablation may not be due entirely to the resolution of edema but may be
      related to chemotoxicity.

PMID- 16801666
TI  - Intracranial dermoid cyst rupture with subarachnoid and intraventricular fat
      dissemination.

PMID- 16801667
TI  - Predictors of outcome after temporal lobectomy for the treatment of intractable
      epilepsy.
AB  - To assess short- and long-term seizure freedom, the authors reviewed 371 patients
      who underwent anterior temporal lobectomy to treat pharmacoresistant epilepsy.
      The mean follow-up duration was 5.5 years (range 1 to 14.1 years). Fifty-three
      percent of patients were seizure free at 10 years. The authors identified
      multiple predictors of recurrence. Results of EEG performed 6 months
      postoperatively correlated with occurrence and severity of seizure recurrence, in
      addition to breakthrough seizures with discontinuation of antiepileptic drugs.

PMID- 16801668
TI  - Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized
      controlled study.
AB  - Elevated homocysteine is associated with increased risk of heart disease, stroke,
      and dementia. Therapy of Parkinson disease (PD) with levodopa elevates
      homocysteine. The authors conducted a 6-week, multicenter, randomized, double
      blind, placebo-controlled trial to test whether folate 1 mg/vitamin B(12) 500
      microg or entacapone reduced serum homocysteine in 35 levodopa-treated PD
      patients. Levodopa initiation caused a small elevation in homocysteine. Vitamin
      therapy, but not entacapone, resulted in a decrease in homocysteine compared to
      placebo.

PMID- 16801669
TI  - Anti-inflammatory cytokines in subclinical carotid atherosclerosis.
AB  - Some studies have shown correlations between selected proinflammatory factors and
      carotid atherosclerosis. It has not been established whether anti-inflammatory
      cytokines are associated with carotid intima-media thickness (IMT), an ultrasound
      surrogate marker of atherosclerosis. Therefore, the authors studied the
      relationship between the carotid IMT and serum levels of interleukin (IL)-10 and
      transforming growth factor-beta1 in 76 subjects. They discovered that lower IL-10
      levels were associated with increased mean IMT in common carotid arteries.

PMID- 16801670
TI  - Family history of dementia is a risk factor for Lewy body disease.
AB  - Genetic factors are important in Alzheimer disease (AD) and Parkinson disease but
      have not been well characterized in Lewy body dementia (LBD). The authors
      obtained family history in patients from an autopsy series of AD and LBD and in
      living healthy controls. A family history of dementia was more common in both LBD
      and AD compared with controls, suggesting that genetic factors are as important
      in LBD as they are in AD.

PMID- 16801671
TI  - Distinguishing early-onset PD from dopa-responsive dystonia with transcranial
      sonography.

PMID- 16801672
TI  - Dextromethorphan-induced neurologic illness in a patient with negative toxicology
      findings.

PMID- 16801673
TI  - Relapsing demyelinating disease after chicken pox in a child.

PMID- 16801674
TI  - Unmasking of autoimmune hepatitis in a patient with MS following interferon beta
      therapy.

PMID- 16801675
TI  - The Thr354Ile substitution in PSEN1:: disease-causing mutation or polymorphism?

PMID- 16801676
TI  - Isolated inferior rectus palsy due to midbrain infarction detected by diffusion
      weighted MRI.

PMID- 16801678
TI  - Clipping vs coiling of posterior communicating artery aneurysms with third nerve
      palsy.

PMID- 16801680
TI  - Personal history: the pipes of pan.

PMID- 16801679
TI  - Treatment and prevention of the amyloidoses: can the lessons learned be applied
      to sporadic inclusion-body myositis?

PMID- 16801681
TI  - Significance of phrenic nerve electrophysiological abnormalities in Guillain
      Barre syndrome.

PMID- 16801683
TI  - Neurotrophic enhancers as therapy for behavioral deficits in rodent models of
      Huntington's disease: use of gangliosides, substituted pyrimidines, and
      mesenchymal stem cells.
AB  - The interest in using neurotrophic factors as potential treatments for
      neurodegenerative disorders, such as Huntington's disease, has grown in the past
      decade. A major impediment for the clinical utility of neurotrophic factors is
      their inability to cross the blood-brain barrier in therapeutically significant
      amounts. Although several novel mechanisms for delivering exogenous neurotrophins
      to the brain have been developed, most of them involve invasive procedures or
      present significant risks. One approach to circumventing these problems is using
      therapeutic agents that can be administered systemically and have the ability to
      enhance the activity of neurotrophic factors. This review highlights the use of
      gangliosides, substituted pyrimidines, and mesenchymal stem cells as neurotrophic
      enhancers that have significant therapeutic potential while avoiding the pitfalls
      of delivering exogenous neurotrophic factors through the blood-brain barrier. The
      review focuses on the potential of these neurotrophic enhancers for treating the
      behavioral deficits in rodent models of Huntington's disease.

PMID- 16801682
TI  - The phosphoinositide kinase PIKfyve/Fab1p regulates terminal lysosome maturation
      in Caenorhabditis elegans.
AB  - Membrane dynamics is necessary for cell homeostasis and signal transduction and
      is in part regulated by phosphoinositides. Pikfyve/Fab1p is a phosphoinositide
      kinase that phosphorylates phosphatidylinositol 3-monophosphate into
      phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] and is implicated in
      membrane homeostasis in yeast and in mammalian cells. These two phosphoinositides
      are substrates of myotubularin phosphatases found mutated in neuromuscular
      diseases. We studied the roles of phosphatidylinositol phosphate kinase 3 (PPK
      3), the orthologue of PIKfyve/Fab1p, in a multicellular organism, Caenorhabditis
      elegans. Complete loss of ppk-3 function induces developmental defects
      characterized by embryonic lethality, whereas partial loss of function leads to
      growth retardation. At the cellular level, ppk-3 mutants display a striking
      enlargement of vacuoles positive for lysosome-associated membrane protein 1 in
      different tissues. In the intestine, RAB-7-positive late endosomes are also
      enlarged. Membranes of the enlarged lysosomes originate at least in part from
      smaller lysosomes, and functional and genetic analyses show that the terminal
      maturation of lysosomes is defective. Protein degradation is not affected in the
      hypomorphic ppk-3 mutant and is thus uncoupled from membrane retrieval. We
      measured the level of PtdIns(3,5)P2 and showed that its production is impaired in
      this mutant. This work strongly suggests that the main function of PPK-3 is to
      mediate membrane retrieval from matured lysosomes through regulation of
      PtdIns(3,5)P2.

PMID- 16801685
TI  - Perception of emotional prosody: moving toward a model that incorporates sex
      related differences.
AB  - The overall purpose of this article is to review the literature that addresses
      the theoretical models, neuroanatomical mechanisms, and sex-related differences
      in the perception of emotional prosody. Specifically, the article focuses on the
      right-hemisphere model of emotion processing as it pertains to the perception of
      emotional prosody. This article also reviews more recent research that implicates
      a role for the left hemisphere and subcortical structures in the perception of
      emotional prosody. The last major section of this article addresses sex-related
      differences and the potential influence of hormones on the perception of
      emotional prosody. The article concludes with a section that offers directions
      for future research.

PMID- 16801684
TI  - Neuronal implementation of hippocampal-mediated spatial behavior: a comparative
      evolutionary perspective.
AB  - The hippocampal formation (HF) of mammals and birds plays a strikingly similar
      role in the representation of space. This evolutionarily conserved property,
      however, belies the contrasting spatial ecology of animals such as rats and
      homing pigeons, differing spatial ecologies that should have promoted the
      evolution of group-specific adaptations to the HF representation of space.
      However, the spatial response properties of pigeon and rat HF neurons reveal
      surprising similarity in the contribution of position, direction, and trajectory
      toward explaining spatial variation in firing rate. By contrast, the asymmetrical
      distribution of neuronal response properties in the left and right HF of homing
      pigeons, but not rats, indicates a difference in network organization. The
      authors propose that hippocampal evolution may be characterized by inertia with
      respect to changes in the basic spatial elements that determine the response
      properties of neurons but considerable plasticity in how the neuronal response
      elements are organized into functional networks.

PMID- 16801686
TI  - Re: Recalcitrant patellar tendinosis in elite athletes: surgical treatment in
      conjunction with aggressive postoperative rehabilitation.

PMID- 16801687
TI  - Re: Femoral press-fit fixation technique in anterior cruciate ligament
      reconstruction using bone-patellar tendon-bone graft: a prospective clinical
      evaluation of 285 patients.

PMID- 16801689
TI  - Postoperative subscapularis muscle insufficiency after primary and revision open
      shoulder stabilization.
AB  - BACKGROUND: Postoperative subscapularis muscle insufficiency after open shoulder
      stabilization procedures represents an unrecognized condition. HYPOTHESIS:
      Primary and revision open shoulder stabilization using the inverted L-shaped
      tenotomy approach impairs subscapularis muscle recovery and affects final
      clinical outcome. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS:
      Twenty-five patients who underwent primary (group 1: n = 13; mean age, 36.5
      years; follow-up, 48 months) or revision (group 2: n = 12; mean age, 34.2 years;
      follow-up, 52 months) open shoulder stabilization procedures were followed up
      clinically (clinical subscapularis tests and signs, Constant score, and Rowe
      score) and by magnetic resonance imaging (tendon integrity, defined muscle
      diameters, and signal intensity analysis [ratio infraspinatus/upper subscapularis
      muscle and infraspinatus/lower subscapularis muscle]). A third group (group 0) of
      12 healthy volunteers served as a control. RESULTS: Clinical signs for
      subscapularis muscle insufficiency were present in 53.8% of cases in group 1 and
      91.6% of cases in group 2. There were no significant differences between groups
      with regard to Constant and Rowe scores (P > .05). On magnetic resonance imaging,
      no complete tendon ruptures were found. The mean vertical diameter of the
      subscapularis muscle and the mean transverse diameter of the upper subscapularis
      muscle portion were significantly greater in group 0 than in group 1 and greater
      in group 1 than in group 2 (P < .05). The mean transverse diameter of the lower
      subscapularis muscle was comparable in all groups (P > .05). The signal intensity
      analysis revealed the infraspinatus/upper subscapularis muscle ratio was greater
      in group 0 than in group 1 and greater in group 1 than in group 2 (P < .05). The
      infraspinatus/lower subscapularis muscle ratio was lower in group 0 than in
      groups 1 and 2 (P < .05). CONCLUSION: Open shoulder stabilization using an
      inverted L-shaped tenotomy approach may lead to atrophy and fatty infiltration,
      particularly of the upper part of the subscapularis muscle, resulting in
      postoperative subscapularis muscle insufficiency. Revision procedures using the
      same approach may further compromise clinical subscapularis muscle function and
      structure. The lower portion of the subscapularis muscle seems to have a
      compensating effect that may, in addition to a meticulous capsulolabral
      reconstruction, account for the uncompromised overall clinical outcome.

PMID- 16801690
TI  - Dynamic ultrasound as a selection tool for reducing achilles tendon reruptures.
AB  - BACKGROUND: The optimal method of treatment for acute tendo-Achilles ruptures
      continues to be debated. HYPOTHESIS: The reported lower rerupture rate for
      operatively treated patients is an effect of tendon end apposition during the
      healing process, and patients in whom apposition can be demonstrated using
      ultrasound will have a similar rate of rerupture if treated nonoperatively. STUDY
      DESIGN: Cohort study; Level of evidence, 2. METHOD: The authors reviewed all
      patients with an Achilles tendon rupture who were treated to a standard protocol
      during a 5-year period (2000-2005). Patients with a gap of 5 mm or more in
      equinus on ultrasound underwent surgery; those with a gap of less than 5 mm
      received nonoperative treatment. All patients were followed up to a minimum of 12
      months. RESULTS: After exclusions, 125 patients were included: 67 treated
      operatively and 58 nonoperatively. There were 2 reruptures in the nonoperative
      group and 1 with surgery. There was no significant difference between the groups
      for any complication. CONCLUSION: Reduction of rerupture and surgery risks may be
      possible using dynamic ultrasound case selection. Further studies are needed to
      show whether functional results are the same with surgical and nonsurgical
      treatment when dynamic ultrasound criteria are used for case selection.

PMID- 16801691
TI  - A prospective, randomized clinical investigation of the treatment of first-time
      ankle sprains.
AB  - BACKGROUND: Acute ankle ligament sprains are treated with the use of controlled
      mobilization with protection provided by external support (eg, functional
      treatment); however, there is little information regarding the best type of
      external support to use. HYPOTHESIS: There is no difference between elastic
      wrapping, bracing, bracing combined with elastic wrapping, and casting for
      treatment of acute, first-time ankle ligament sprains in terms of the time a
      patient requires to return to normal function. STUDY DESIGN: Randomized
      controlled clinical trial; Level of evidence, 1. METHODS: Patients suffering
      their first ligament injury were stratified by the severity of the sprain (grades
      I, II, or III) and then randomized to undergo functional treatment with different
      types of external supports. The patients completed daily logs until they returned
      to normal function and were followed up at 6 months. RESULTS: Treatment of grade
      I sprains with the Air-Stirrup brace combined with an elastic wrap returned
      subjects to normal walking and stair climbing in half the time required for those
      treated with the Air-Stirrup brace alone and in half the time required for those
      treated with an elastic wrap alone. Treatment of grade II sprains with the Air
      Stirrup brace combined with the elastic wrap allowed patients to return to normal
      walking and stair climbing in the shortest time interval. Treatment of grade III
      sprains with the Air-Stirrup brace or a walking cast for 10 days followed by
      bracing returned subjects to normal walking and stair climbing in the same time
      intervals. The 6-month follow-up of each sprain severity group revealed no
      difference between the treatments for frequency of reinjury, ankle motion, and
      function. CONCLUSION: Treatment of first-time grade I and II ankle ligament
      sprains with the Air-Stirrup brace combined with an elastic wrap provides earlier
      return to preinjury function compared to use of the Air-Stirrup brace alone, an
      elastic wrap alone, or a walking cast for 10 days.

PMID- 16801692
TI  - Digital radiographic evaluation of medial joint space narrowing after partial
      meniscectomy of bucket-handle medial meniscus tears in anterior cruciate ligament
      intact knees.
AB  - BACKGROUND: Few studies exist that evaluate the effect of partial medial
      meniscectomy in knees with intact anterior cruciate ligaments. HYPOTHESIS:
      Partial meniscectomy of bucket-handle medial meniscus tears will cause joint
      space narrowing. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Between 1982 and 2001, 135 patients met the study criteria of a partial medial
      meniscectomy, intact ligaments, no surgery to the contralateral knee, and no
      chondromalacia greater than grade II. Seventy-nine patients living within 150
      miles of the clinic were asked to return for physical examination. Joint space
      narrowing was measured from the middle of the femoral condyle to the middle of
      the tibial plateau using digitally magnified weightbearing 45 degrees flexed
      posteroanterior and full-extension anteroposterior radiographs. Measurements were
      performed twice with the observer blinded to the previous measurements.
      Subjective follow-up was obtained prospectively on an annual basis with
      International Knee Documentation Committee and modified Noyes knee
      questionnaires. RESULTS: Forty-nine patients were examined at a mean of 11.8
      years postoperatively. Mean medial joint space narrowing was 1.2 +/- 0.5 mm on 45
      degrees flexed posteroanterior radiograph and 0.2 +/- 0.9 mm on full-extension
      anteroposterior radiographs (P < .001). Four patients had 2 mm or more of joint
      space narrowing. Subjective surveys obtained from 95 patients showed a mean
      subjective score of 89.9 points. Subjective scores did not decrease through time,
      and there was no correlation of joint space narrowing to lower subjective scores.
      CONCLUSION: Partial medial meniscectomy in stable knees causes only mild joint
      space narrowing (mean, 1.2 mm) at a mean 12-year follow-up. Digitally magnified
      45 degrees flexed posteroanterior radiographs are more likely to demonstrate
      joint space narrowing than are full-extension anteroposterior radiographs.

PMID- 16801693
TI  - Outbreak of human listeriosis associated with tomme cheese in northwest
      Switzerland, 2005.
AB  - During an eight week period in spring 2005, 10 cases of listeriosis were reported
      in a small area of northwest Switzerland (150,000 inhabitants). Eight cases were
      in older immunocompromised patients who became ill with bacteraemia (three
      deaths), and two cases were in pregnant women who had septic abortion. All cases
      were due to a serotype 1/2a isolate with one of two pulsovars found by PFGE.
      Patient interviews quickly revealed that a locally made and distributed soft
      cheese (known as 'tomme') was the food source responsible for the outbreak.
      Samples of this cheese, and of butter made in the same factory, revealed Listeria
      monocytogenes sv 1/2a of the same pulsovar in amounts of 1000-10 000 and 10-100
      cfu/g, respectively. The prompt suspension of production, the market recall of
      the product, and a public alert terminated the outbreak. However, two cases of
      febrile gastroenteritis due to the same strains were reported within 10 days of
      product recall. The restricted distribution area of the contaminated cheese and
      the collaboration of local physicians, medical microbiologists and food health
      services all contributed to a rapid and successful investigation. This small
      outbreak of listeriosis reinforces the need for a laboratory-based surveillance
      system with rapid typing, as well as collaboration between physicians and
      microbiologists.

PMID- 16801694
TI  - Listeria outbreak associated with sandwich consumption from a hospital retail
      shop, United Kingdom.
AB  - An outbreak of listeriosis occurred in the Swindon area of the UK in autumn 2003.
      Five cases were detected in pregnant women. Four of these women were thought to
      have eaten prepacked sandwiches from a retail outlet in one particular hospital.
      Sampling at the supplier detected Listeria monocytogenes, which was
      indistinguishable on molecular testing from the patients isolates. Recent changes
      in UK food legislation should help diminish the risk of further outbreaks/cases
      such as ours occurring.

PMID- 16801695
TI  - Significant increase of listeriosis in Germany--epidemiological patterns 2001
      2005.
AB  - Listeriosis has been a mandatorily notifiable disease in Germany since January
      2001. Clinical cases with isolation of Listeria monocytogenes from sterile
      specimens or neonates are reported to the Robert Koch-Institut. Listeriosis
      incidence significantly increased from 0.26 per 100 000 inhabitants (217 cases)
      in 2001 to 0.62 per 100 000 (519 cases) in 2005. The increase only occurred among
      non pregnancy-associated cases and was mainly due to a rise in cases in the age
      group > or =60 years. The highest incidences were observed in neonates and adults
      > or =70 years. Male cases predominated, except for cases occurring in adults of
      child-bearing age. The overall case fatality rate was 9%. No temporal or spatial
      clusters of cases were observed and no outbreaks with a common source vehicle
      were identified. In 46% of the cases malignancies were reported as predisposing
      factor. Reasons for the increase of listeriosis in Germany remain unclear. The
      newly implemented surveillance system, and raised diagnostic awareness, cannot
      explain the particularly high increase in incidence from 2004 to 2005. Increased
      contamination of common foodstuffs or changes in underlying medical conditions or
      treatment options may have contributed to the increase. A project for enhanced
      listeriosis surveillance was begun in 2005 to obtain more detailed information
      about the clinical course, underlying conditions, medical treatment, knowledge
      about listeriosis and possible food risk factors from all newly diagnosed cases.
      For better outbreak detection, a nationwide system for molecular subtyping of
      listeria strains from humans and food is necessary. Recommendations for
      prevention should be extended to all risk groups with predisposing conditions

PMID- 16801696
TI  - Surveillance of listeriosis in Finland during 1995-2004.
AB  - We analysed the surveillance data from listeriosis cases notified to the Finnish
      National Infectious Diseases Register between 1995 and 2004 and describe our
      recent experience in investigating clusters of listeriosis cases. The number of
      annual cases varied between 18 and 53 but no trends in incidence were identified
      (average annual incidence was 7 cases per million inhabitants). Only a few cases
      affected pregnant women or newborns. Most of the patients were elderly people
      with non-malignant underlying illnesses; 25% of them died from their infections.
      By routine sero- and genotyping of the listeria isolates, we detected several
      clusters; the vehicle for infection was only identified for two outbreaks. At
      least one quarter of listeriosis cases (78/315) was caused by a certain sero
      genotype or closely related genotypes, which have also been found from vacuum
      packed cold-smoked or cold-salted fish products. During 2000-2003, Finnish
      consumers were repeatedly informed about food precautions for risk groups. The
      information was also given to attending physicians and prenatal clinics.

PMID- 16801697
TI  - Surveillance of human listeriosis in France, 2001-2003.
AB  - Mandatory notification of listeriosis began in France in 1999. Enhanced public
      health surveillance, including routine molecular characterisation of Listeria
      monocytogenes strains, epidemiologic follow up of cases, and collection of food
      samples, has improved the sensitivity of outbreak detection and response. The
      incidence of listeriosis declined from 4.5 cases/million in 1999-2000 to
      approximately 3.5 cases/million during the period 2001-2003. Clinical,
      demographic and microbiological characteristics of listeriosis in France remained
      stable during this time period. Maternal-fetal infections accounted for 24% of
      all cases. Serovar 4b accounted for 49% of cases and 60% of case clusters. The
      incidence of listeriosis in France has declined and is now lower than in several
      other European countries.

PMID- 16801698
TI  - Listeria in Europe: the need for a European surveillance network is growing.

PMID- 16801699
TI  - Two fatal human infections with avian influenza H5, Turkey, January 2006.

PMID- 16801700
TI  - Very little influenza activity in Europe up until the end of 2005.

PMID- 16801702
TI  - More cases of avian influenza infection in humans and poultry in Turkey.

PMID- 16801703
TI  - Research suggests avian influenza may affect more humans than previously thought.

PMID- 16801704
TI  - Ensuring prudent use of antimicrobials in human medicine: forceful action needed
      in Europe.

PMID- 16801705
TI  - SeqNet.org: a European laboratory network for sequence-based typing of microbial
      pathogens.

PMID- 16801707
TI  - Avian influenza in Turkey: 21 confirmed human cases.

PMID- 16801708
TI  - Human cases of avian influenza in eastern Turkey: the weather factor.

PMID- 16801709
TI  - Tularaemia outbreak in hare hunters in the Darmstadt-Dieburg district, Germany.

PMID- 16801710
TI  - Substantial reduction of human Salmonella Enteritidis infections in Luxembourg in
      2005.

PMID- 16801711
TI  - New rotavirus vaccines protect against diarrhoea in children.

PMID- 16801712
TI  - Management of potential human cases of influenza A/H5N1: lessons from Belgium.

PMID- 16801713
TI  - Clostridium difficile PCR ribotype 027 outbreaks in the Netherlands: recent
      surveillance data indicate that outbreaks are not easily controlled but
      interhospital transmission is limited.

PMID- 16801714
TI  - Urgent action needed to stop spread of hepatitis B and C in Estonian drug users.

PMID- 16801715
TI  - Variant Creutzfeldt-Jakob disease in the United Kingdom and elsewhere: situation
      at the end of 2005.

PMID- 16801716
TI  - HIV and AIDS in the United Kingdom African communities: guidelines produced for
      prevention and care.

PMID- 16801717
TI  - HBV viral load is an independent predictor of progression to hepatocellular
      carcinoma in chronic HBV patients.

PMID- 16801719
TI  - National Institute on Alcohol Abuse and Alcoholism and the study of fetal alcohol
      spectrum disorders. The International Consortium.
AB  - Fetal alcohol syndrome (FAS) is a large and rapidly increasing public health
      problem worldwide. Aside the full-blown FAS, multiple terms are used to describe
      the continuum of effects that result from prenatal exposure to alcohol, including
      the whole fetal alcohol spectrum disorders (FASD). The revised Institute of
      Medicine (IOM) Diagnostic Classification System and the diagnostic criteria for
      FAS and FASD are reported, as well as the formation of the four-state FAS
      International Consortium and its aims, as the development of an information base
      that systematizes data collection that helps to determine at-high-risk
      populations, and to implement and test a scientific-based prevention/intervention
      model for at risk women. The Consortium was further enlarged, with the inclusion
      of some more states (including Italy), leading to the formation of the
      International Consortium for the Investigation of FASD. The objectives of the
      Consortium are reported, as well as its previous activities, the South Africa and
      Italy Projects (active case ascertainment initiatives), and its future
      activities.

PMID- 16801720
TI  - Individual susceptibility and alcohol effects:biochemical and genetic aspects.
AB  - The large interethnic and interindividual variability in alcohol-induced toxic
      effects comes from a combination of genetic and environmental factors,
      influencing ethanol toxicokinetics. The hepatic enzymatic systems involved in
      ethanol metabolism are alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)
      and microsomal P4502E1 (CYP2E1). ADH oxidizes ethanol to acetaldehyde, which is
      very efficiently oxidized to acetate by ALDH. About 10% of moderate quantities of
      ethanol is metabolised by CYP2E1; the percentage increases when ADH is saturated.
      During ethanol metabolism reactive oxygen species and hydroxyethyl radicals are
      generated, causing oxidative stress, responsible for most ethanol-induced liver
      damage. For their critical role in detoxifying radicals, glutathione S
      transferase are gaining attention in the etiology of alcoholism. All these
      enzymes have been shown to be polymorphic, giving rise to altered phenotypes. For
      this reason recent studies have looked for a correlation between metabolic
      variability and differences in alcohol abuse-related effects.

PMID- 16801721
TI  - Alcohol intake during prenatal life affects neuroimmune mediators and brain
      neurogenesis.
AB  - Several lines of evidence suggest that alcohol exposure during prenatal
      gestation, or during early postnatal life may be a risk factor for the
      manifestation of neurological and for immune-related disorders in later life. The
      cellular, biochemical and molecular mechanisms of ethanol toxicity, however, have
      not been yet clearly established. Recent studies indicated that neurotrophin
      signaling pathways may be involved in ethanol mediated cell death. The present
      investigation addressed the question of whether nerve growth factor (NGF), which
      is the first and best characterized member of the neurotrophin family, and NGF
      target cells are affected by prenatal exposure to alcohol. The result of our
      study indicates that NGF synthesis and the functional activity of NGF-target
      cells localized in the brain are markedly influenced by ethanol intake. The
      possible link between such changes and the hypothesis that these alterations may
      contribute to certain of the neuropathology observed following alcohol exposure
      would be discussed.

PMID- 16801722
TI  - Exposure to low and moderate doses of alcohol on late gestation modifies
      infantile response to and preference for alcohol in rats.
AB  - Several studies in rats have found that maternal administration of low or
      moderate doses of ethanol result in fetal perception of the chemosensory and
      toxic effects of ethanol. This prenatal experience with the drug enhances the
      palatability of ethanol's flavor and increases ethanol consumption during infancy
      and adolescence. The acquired preference for ethanol seems to be a conditioned
      response established prenatally, by the association of ethanol's sensory and
      reinforcing aspects, the latter mediated by the opioid system. These results are
      in accordance with data of studies in humans, and should be taken into account
      for clinical studies analyzing the relationship between prenatal ethanol exposure
      and later ethanol abuse problems.

PMID- 16801723
TI  - Female drinking, environment and biological markers.
AB  - The rate of women involved in alcohol abuse is rapidly increasing and the age of
      first use tends dramatically to decrease. The health and social costs are high
      both for the adverse effects on physical and psychological woman health, and for
      the teratogenic effect of alcohol on fetal development. The review takes in
      account physiological aspects of alcohol effects according to age and gender
      differences. Interaction between alcohol habit and environment are discussed
      together with the risk of co-exposure to alcohol and pollutants. The role of
      biomarkers may be invaluable for clinical utility, prevention and early
      intervention above all to avoid prenatal, not reversible damages. The update of
      alcohol studies shows the greater severity of alcohol damage in female and the
      need of gender-targeted intervention.

PMID- 16801724
TI  - Diagnosis of fetal alcohol spectrum disorder (FASD): fatty acid ethyl esters and
      neonatal hair analysis.
AB  - Measuring levels of fatty acid ethyl esters (FAEE) in hair has been recently
      shown to discriminate between adult heavy and non-drinkers. Here, we review the
      potential of neonatal FAEE measurement in detecting infants exposed to alcohol in
      utero by outlining current progress in the development of a neonatal hair test
      for the diagnosis of fetal alcohol spectrum disorder (FASD). Developing a
      reproducible, accurate and predictable hair test for FAEE measurements in
      neonatal hair may prove to be a powerful tool in the detection of in utero
      alcohol exposure which is needed for the diagnosis of FASD. Such a neonatal hair
      test can revolutionize current FASD diagnostic methodology by providing early
      diagnosis, allowing intervention and treatment at stages where the adverse
      effects of alcohol can still be mitigated.

PMID- 16801725
TI  - Brain imaging and fetal alcohol spectrum disorders.
AB  - Over thirty years of research has revealed that prenatal exposure to alcohol has
      a devastating impact on the structure and function of the developing central
      nervous system. Imaging studies over the past ten years have improved our
      understanding of the structural alterations related to prenatal alcohol exposure
      and provided researchers with potential hypotheses for brain-behavior
      relationships. Structural alterations associated with prenatal alcohol exposure
      have been found in overall brain size, shape, and symmetry, along with regional
      decreases in white and gray matter. In addition, abnormalities have been noted in
      specific structures such as the cerebellum, basal ganglia, and corpus callosum.
      This review demonstrates that specific areas of the brain may be more vulnerable
      to prenatal exposure to alcohol.

PMID- 16801727
TI  - Educational planning for children with fetal alcohol syndrome.
AB  - It has now been thirty-two years since Jones and Smith first identified fetal
      alcohol syndrome (FAS) in the United States. Since then, numerous epidemiology
      studies have been conducted to determine prevalence rates of this disorder. More
      recently, the research focus has concentrated on studies to elucidate a
      neurobehavioral phenotype for the alcohol-exposed population. As a result, the
      FAS field has learned what types of neurobehavioral issues occur most frequently
      with these children. This paper discusses the results of neurobehavioral research
      with alcohol exposed children and how that information can be used to inform
      school assessment, intervention planning, and support.

PMID- 16801726
TI  - Fetal alcohol syndrome disorders: experience on the field. The Lazio study
      preliminary report.
AB  - In Italy, little is known about the problems related to alcohol drinking during
      pregnancy. In this paper, the Italian literature about this subject is briefly
      reviewed. This first Italian experience of a field study, aimed to the assessment
      of the prevalence of fetal alcohol syndrome (FAS) and fetal alcohol spectrum
      disorders (FASD) in an area in the Rome province (Lazio region) is reported. This
      in-field study was performed in the school years 2003-2004 and 2004-2005 in
      cooperation with American researchers, most from University of New Mexico
      (Albuquerque), and Italian researchers from University "la Sapienza" of Rome.
      First grade children (n(o) = 1,086) of primary school were contacted to enter in
      the in-school study for the detection of FAS and FASD and were examined by the
      experts team of clinicians, pediatrics, psychologists. Preliminary consideration
      and the implications of this study for FASD prevention are discussed.

PMID- 16801728
TI  - Work-related injuries in young workers: an Italian multicentric epidemiological
      survey.
AB  - Emergency departments records from 33 hospitals were reviewed to disclose work
      related injuries occurred in teen-subjects living in 14 Italian cities. During
      January-June 2000, 317 work-related injuries were reported. Male subjects, 17
      year old, working in the industrial field, resulted the most affected, probably
      due to the fact that among young workers this sex and age class is the most
      represented one. Cluster analysis identified two groups of work-related injuries:
      one includes mainly transportation injuries causing lower extremities or multiple
      body sites traumas. The other is more strictly related to specific working tasks
      and includes mostly traumas and cut wounds in hand/wrist and head, together with
      eye lesions. A more intensive supervision on the use of protective equipment, a
      more appropriate training in hazard recognition and safe work practices,
      including operation of vehicles in the work site, must be implemented to reduce
      work-related injuries.

PMID- 16801729
TI  - Italian survey on human behaviour for inhalation exposure assessment.
AB  - In order to support risk management in identifying effective mitigation measures,
      exposure assessment related to environmental pollution needs to integrate
      monitoring of pollution levels and control data with information on population
      behaviour and lifestyle. With this aim, a sample population survey was carried
      out in a Northern Italian city, collecting data on human behavioural factors
      influencing inhalation exposure. Questionnaires gathering data on dwelling
      characteristics, and weekly individual diaries on personal behaviour, such as
      places frequented and daily activities, were used. Data collection was carried
      out in two different seasons, spring-summer and fall-winter. A sample of 270
      families, randomly selected from the municipal registry, was enrolled for each
      seasonal observation. The study allowed quantification of variability in human
      behaviour revealing seasonal variation and differences due to age and gender.
      Daily activity patterns were described and probability distributions of
      inhalation rates were obtained for all observed population groups. A
      probabilistic exposure model was developed and the resulting exposure
      distributions for the two seasonal periods were compared. Results confirm that
      exposure estimates are strongly biased if variability in human behaviour is not
      taken into account.

PMID- 16801730
TI  - [Statistical methods for the analysis of twin data].
AB  - The most important statistical methods currently used for the analysis of twin
      data are described. The main objective of these methods is to estimate the
      contribution of the genetic and environmental factors to the variability of
      normal or pathological human traits, by means of the information obtained from
      monozygotic and dizygotic twin pairs. In this context, the concept of
      heritability becomes relevant. Not only the simple comparison between monozygotic
      and dizygotic twins, based on measures such as the concordance and the
      correlation, but also new and more complex approaches are presented, with a
      special emphasis on the structural equation models, and a synthetic view on the
      DF-analysis and the correlated frailty models. Some examples of applications to
      the data of the Italian Twin Registry are also illustrated.

PMID- 16801731
TI  - [The nerve growth factor induces cutaneous ulcer healing in "non-responder"
      tranplanted skin].
AB  - Nerve growth factor (NGF) is an endogenously produced growth factor regulating
      survival not only of nerve cells, but also of cutaneous tissues. We have recently
      reported that NGF can promote healing of human corneal ulcer, and cutaneous
      diabetic and pressure ulcers. In this study, we present a case report showing
      that NGF can induce recovery of a chronic cutaneous ulcer that failed to respond
      to all available therapies, including autologous skin transplantation. The result
      showed that topical application of NGF for 3 consecutive months induced skin
      ulcer healing and reduced the local inflammation. This finding supports and
      extents previous studies suggesting the cutaneous healing action and the
      potential therapeutic role of NGF.

PMID- 16801732
TI  - [Development of a Japanese Version of the Work-Family Conflict Scale (WFCS), and
      examination of its validity and reliability].
AB  - The purposes of this study were to develop a Japanese version of the multi
      dimensional Work-Family Conflict Scale (WFCS) and to examine its reliability and
      validity. The original 18-item WFCS (Carlson, et al., 2000) has six dimensions of
      conflict which consist of time-based work interference with family (WIF), time
      based family interference with work (FIW), strain-based WIF, strain-based FIW,
      behavior based WIF, and behavior-based FIW. We developed a Japanese version of
      the WFCS from the original WFCS which is written in English by the following
      procedure: forward translation and back translation by several researchers
      including a native English speaker, and finally, gaining the approval of Carlson
      et al., the original authors. A self-administered questionnaire including the
      WFCS was distributed to 180 permanent contract, information technology (IT)
      engineers with pre-school children, who were employed at 24 IT companies, each
      with over 300 employees. Test-retest was conducted on a different group of 34
      parents whose children were attending nursery school. Cronbach's reliability
      coefficients for the six subscales ranged from 0.77 to 0.92, showing sufficiently
      high internal consistency. Only the internal correlation coefficient between
      behavior-based WIF and behavior-based FIW was above 0.60, indicating that
      discriminant validity exists among most of the sub-scales. Also, upon comparison
      of confirmatory factor analysis results among five models, the six-factor model,
      which is the same model used in the original WFCS, showed the best fit (chi
      square=231.82, df=129, CFI=0.95, AIC=315.82, RMSEA=0.07), demonstrating construct
      validity. On test-retest, weighted kappa coefficients of each item and the intra
      class correlations of six subscales, indicated adequate reproducibility. These
      results suggest that the Japanese version of the WFCS may be a reliable and valid
      instrument for assessing the conflict between work and family in Japanese
      workers.

PMID- 16801733
TI  - Exploring the association between anorexia nervosa and geographical latitude.
AB  - OBJECTIVE: This paper explores the relationship between anorexia nervosa (AN) and
      climate by mapping the distribution of references of AN in the literature at
      different latitudes. METHOD: The distributions of the bibliographic references of
      two medical disorders -psoriasis and cataracts-, and four mental disorders -AN,
      anxiety disorders, seasonal affective disorders, and schizophrenia- were mapped
      according to the institutional affiliation of their first author. RESULTS: The
      distribution of references to AN was quite similar to the mental and medical
      disorders associated to high latitudes, although references to AN were more
      frequent in the range of 40 masculine-55 masculine in the Northern Hemisphere.
      DISCUSSION: The psychosocial and sociocultural features of 'cultures' do not
      exhaust the factors defining the environment in which we live. Our findings
      indicate that climatic parameters, such as latitude may be a relevant factor in
      the occurrence of AN.

PMID- 16801734
TI  - Obesity is associated with memory deficits in young and middle-aged adults.
AB  - Recent findings suggest obesity is associated with reduced memory performance in
      older adults. The present study examined whether similar deficits also exist in
      younger adults and the degree to which the relationship between body mass index
      (BMI) and memory varies as a function of age. Prior to inclusion, participants
      were rigorously screened and excluded for medical conditions known to impact
      cognitive functioning, including neurological disorders, head injury,
      cardiovascular disease, and diabetes. A total of 486 healthy adults completed a
      verbal list-learning task. Participants were categorized into normal weight,
      overweight, and obese groups based on their BMI. Performance on learning, delayed
      recall, and recognition performance were compared across BMI groups. Results
      showed obese individuals had poorer memory performance when comparing persons
      across the adult lifespan (age 21-82 yr), but also when examining only younger
      and middle-aged adults (age 21-50 yr). Regression analyses found no evidence of
      an interaction between BMI and age on any memory variable, suggesting the
      relationship between BMI and memory does not vary with age. These findings
      provide further support for an independent relationship between obesity and
      reduced memory performance and suggest these effects are not limited to older
      adults. Further research is needed to identify etiological factors.

PMID- 16801735
TI  - Amenorrhea after weight recover in anorexia nervosa: role of body composition and
      endocrine abnormalities.
AB  - Hypothalamic amenorrhea in anorexia nervosa often precedes weight loss and may
      persist after re-feeding and restoration of a stable normal weight. AIM: To
      assess the rate of persistent amenorrhea in anorexia nervosa (AN) after re
      feeding and the relations of this condition with body composition changes and
      other endocrine parameters. METHODS: A cohort of 250 female outpatients was
      studied to assess persistent amenorrhea prevalence after stable weight recovery.
      Among these, we selected 20 AN female patients (age 16.5-35), 10 with amenorrhea
      (group 1) and 10 with normal menses (group 2). We collected data such as age, age
      at menarche, age at onset of AN, actual body mass index (BMI) and at onset of AN,
      duration of disease. Physical activity has been evaluated as minute per day. The
      following data were obtained: prolactin, growth hormone, estradiol, luteinizing
      hormone, follicle stimulating hormone, thyroid stimulating hormone, free
      triiodothyronine, free thyroxine, free urinary cortisol, serum calcium and
      phosphates, urinary calcium, phosphaturia and alkaline phosphatase. Body
      composition was assessed with a dual energy x-ray absorptiometry (DEXA). RESULTS:
      Thirty-five patients (14%) over a cohort of 250 where still amenorrhoic after
      stable weight recovery. No significance was found in the evaluation of blood
      biochemical tests of the 2 groups. Free urinary cortisol was significantly higher
      in amenorrhoic patients (58.14+/-0.4 vs 15.91+/-9.5), p=0.02. The analysis of
      body composition has shown a percentage of fat of 22.23+/-5.32% in group 1 and of
      26.03%+/-9.1% in group 2, respectively, showing no significant differences.
      Amenorrhoic patients carried on doing a significantly heavier physical activity
      than eumenorrhoic patients. CONCLUSIONS: An adequate body composition and a well
      represented fat mass are certainly a necessary but not sufficient condition for
      the return of the menstrual cycle. Such menstrual cycle recovery would probably
      need other conditions at present being studied and evaluated to occur, such as
      secretory patterns of leptin and its correlations with adrenal function.

PMID- 16801736
TI  - Persistence of anorectic cognitions following a moderate calorie restricted diet.
AB  - Cognitive attitudes and beliefs towards food and body shape are repeatedly
      reported as a maintaining factor of obesity. In order to assess evolution of
      those cognitions following a dietary treatment 18 overweight and obese females
      undergoing a dietary treatment were assessed using the Mizes Anorectic Cognitions
      questionnaire (revised form) before and after a 3-month moderate calorie
      restricted diet. Binge eating status was also assessed in pre-treatment. The main
      finding of the present study is persistence of anorectic cognitions following a
      moderate calorie restricted diet treatment, and furthermore a more pejorative
      evolution of those cognitions in patients with binge symptomatology.

PMID- 16801737
TI  - Fluid intake, personality and behaviour in patients with eating disorders.
AB  - OBJECTIVE: To examine psychological and behavioural variables associated with the
      disordered fluid intake of 112 eating disorder patients. METHOD: Fluid intake
      history for previous seven days, and standardized psychological and behavioural
      measures of eating disorders, mood, personality and health, were completed on
      admission to hospital. RESULTS: Only behaviours associated with eating disorders
      were associated with fluid intake. Greater amounts of total and energy-free
      fluids are consumed if patients report overeating, binge eating and dieting
      between overeating more frequently, drinking more caffeine-containing energy free
      drinks, vomiting and using laxatives. Energy-containing fluid intake is higher if
      patients feel their body weight is less important and if they binge eat. There is
      a significant difference in the amount of fluid drunk (ml or ml/kg) by patients
      with bulimia nervosa (BN) when compared to patients with no current diagnosis but
      not compared with anorexia nervosa (AN) or eating disorders not otherwise
      specified (EDNOS) patients. DISCUSSION: Fluid intake is associated with eating
      disorder behaviour rather than personality and psychological variables. Patients
      eating more drink more.

PMID- 16801738
TI  - Does metabolic syndrome mitigate weight loss in overweight Mexican American women
      treated for 1-year with orlistat and lifestyle modification?
AB  - AIMS: To investigate the effects of a pharmacotherapy (orlistat) plus lifestyle
      management (OLM) intervention on weight loss in Mexican American women with and
      without metabolic syndrome (MS). METHODS: One hundred and seven female
      participants aged 21-65 years and of Mexican origin were randomized to either OLM
      or a wait-list control group (WLC) for one year. The lifestyle interventions were
      tailored to exhibit features of the Mexican culture. Within each group, subjects
      with MS were compared to those without MS to assess whether its presence
      mitigates weight loss. Risk factors for MS also were assessed. RESULTS:
      Participants with MS in the OLM group experienced significant decreases in weight
      and body mass index (BMI) as compared to participants without MS. Participants
      with MS in the OLM group and who completed the study lost 9.3+/-7.5 kg (20.5+/
      16.5 lb) as compared to participants with MS in the WLC group, who only lost
      0.2+/-3.1 kg (0.4+/-6.8 lb). Further, participants with MS in the OLM group who
      completed the study experienced a 3.1+/-3.9 kg/m2 decrease in BMI whereas
      participants with MS in the WLC group only experienced a 0.1+/-1.2 kg/m2 decrease
      in BMI. No changes in other MS risk factors were significant. CONCLUSIONS:
      Patients with MS experienced significant weight loss and decreases in BMI as a
      result of a lifestyle and pharmacotherapy intervention.

PMID- 16801739
TI  - Dynamic monitoring of restricted eating disorders by indirect calorimetry: a
      useful cognitive approach.
AB  - OBJECTIVE: Outpatient treatment in restricted eating disorder: indirect
      calorimetry during dynamic monitoring. DESIGN: A retrospective observational
      study. SUBJECTS: Twenty seven women affected by restricted eating disorder
      (essentially anorexia nervosa) with a body mass index [weight (kg)/height (m2)]
      of 17.29+/-2.47 were studied. The sample was compared as itself control during
      rehabilitative way. INTERVENTIONS: Fat mass (FM) and fat free mass (FFM) were
      determined by anthropometry technique. REE/day and respiratory quotient
      (RQ,VCO2/VO2) were measured by indirect calorimetry using a Calorimeter Vmax 29n
      Sensor Medics-California. Skinfold thickness and circumferences were also
      measured. Arm muscle area (AMA) and fat area were calculated by formulas reported
      in Frisancho. RESULTS: The data indicated a positive correlation between AMA,
      VO2/ml/min and resting energy expenditure (REE)/day values examined during follow
      up of patients. The increase of these parameters indicated a good monitoring
      index correlated to a FFM recovery during psychonutritional rehabilitation.
      CONCLUSION: Indirect calorimetry represents a useful approach for determining REE
      and prescribing diets in these patients. Moreover, the combined use of
      anthropometric techniques allows to accurately assess and adjust therapy
      according to the patient's progress. This study shows that restricted eating
      disorders are characterized by a recovery of FFM related to improvement of body
      weight and REE/day. On the contrary, the increase of AFA revealed a recovery of
      fat-metabolism (corresponding to RQ decrease) and lipid/carbohydrates oxidation
      improvement, only in the presence, at the same time, of O2 consumption increase.

PMID- 16801740
TI  - The Body Uneasiness Test (BUT): development and validation of a new body image
      assessment scale.
AB  - OBJECTIVE: To investigate the psychometric properties of the Body Uneasiness Test
      (BUT), a 71-item self-report questionnaire that consists of two parts: BUT*A
      which measures weight phobia, body image concerns, avoidance, compulsive self
      monitoring, detachment and estrangement feelings towards one's own body
      (depersonalization); and BUT*B which looks at specific worries about particular
      body parts or functions. METHODS: We recruited a clinical sample of 531 subjects
      (491 females) suffering from eating disorders and a general population sample of
      3273 subjects (2016 females) with BMI <25 and Eating Attitudes Test-26 scores
      under the cut-off 20. RESULTS: The exploratory and confirmatory analyses
      confirmed a structural five-factor model for BUT*A and an eight-factor model for
      BUT*B. Internal consistency was satisfactory. The test-retest correlation
      coefficients were highly significant. Concurrent validity with other tests
      (Eating Disorder Inventory, EDI-2; Eating Attitudes Test, EAT-26; Symptom Check
      List, SCL-90R and Coopersmith Self-Esteem Inventory, SEI) was evaluated.
      Normative values for BUT scores in non-clinical samples of normal-weight non
      eating disordered subjects, from adolescence to old age, males and females, were
      calculated. The differences between males and females were highly significant,
      above all in the 18-39-age range. As for the comparison between women with eating
      disorders and controls, the results demonstrated a good predictive validity for
      anorexia nervosa and bulimia nervosa. CONCLUSIONS: The BUT is psychometrically
      sound. It can be a valuable tool for the screening and the clinical assessment of
      abnormal body image attitudes and eating disorders.

PMID- 16801741
TI  - Alexithymia in female patients with eating disorders.
AB  - Previous studies indicate that patients with eating disorders have alexithymic
      characteristics, as revealed by the Toronto Alexithymia Scale (TAS). The aim of
      the present study was to investigate the role of negative affect (anxiety and
      depression) in the relationship between eating disorders and alexithymia. In
      addition, we have evaluated whether the relationship between negative affect and
      alexithymia varies according to the type of eating disorder (anorexia and
      bulimia). Eighteen female patients and 16 female patients who met the Diagnostic
      and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnostic
      criteria for restrictive anorexia nervosa and bulimia nervosa, respectively, and
      18 healthy female controls matched by age and education were submitted to Beck
      Depression Inventory and Spielberger State-Trait Anxiety Inventory to assess
      depression and anxiety and the Toronto Alexithymia Scale (TAS-20) and the Bermond
      Vorst Alexithymia Questionnaire (BVAQ) to evaluate alexithymic characteristics.
      The findings indicated that, although anorexic and bulimic patients showed higher
      alexithymia scores compared to controls, this result could be mainly related to
      negative affect. In fact, taking negative affect into account, anorexic and
      bulimic patients did not show higher TAS-20 and BVAQ scores compared to controls.
      The only variable useful to discriminate among anorexics, bulimics and controls
      is the perceived inability to experience emotional feelings, which is higher in
      anorexic patients compared to the other two groups.

PMID- 16801742
TI  - Conservative treatment of obesity in an academic obesity unit. Long-term outcome
      and drop-out.
AB  - OBJECTIVE: The aim of this study was to explore the outcome and the problems of
      drop-out in the treatment of obese outpatients at an academic obesity unit.
      DESIGN: A two-year clinical treatment evaluation. SUBJECTS: A total of 117 obese
      subjects, 83 women and 34 men, mean aged 50 (23-70) years, with an average body
      mass index (BMI) of 39.0 kg/m2 (28.8- 64.7). INTERVENTION: All treatment was
      based on group therapy and included behaviour modification and nutrition
      counselling. A team of nurses, dieticians, a physiotherapist, a psychotherapist
      and a physician supervised the treatment. Two programmes were used. Group 1
      initially received a low-calorie diet (LCD) for seven weeks combined with the
      behaviour treatment programme. Group 2 was treated with the behaviour treatment
      programme only. All subjects were offered complementary treatment according to
      their medical needs. RESULTS: There was a continuous drop-out of subjects during
      the two-year treatment period with an overall drop-out rate of 53%.
      Anthropometric characteristics, medical history or reasons for drop-out had no
      impact on the drop-out rate. In completers the weight reduction after two years
      was 9.2 [+/-10.8 standard deviation (S.D.) kg. In non-completers the weight
      reduction of the last observed weight measurement was 4.7 (+/-7.9 S.D.) kg. After
      year two, the weight reduction in Group 1 was 8.8 (+/-12.2 S.D.) kg, and in Group
      2 was 9.7 (+/-8.0 S.D.) kg. CONCLUSION: This study has showed the difficulties of
      long-term clinical treatment of obese outpatients, even in a specialised obesity
      clinic. The findings demonstrate that educated and experienced staff together
      with an extended package of treatment options is not enough to keep patients in
      treatment for two years. However though the drop-out rate was high, two thirds of
      the included subjects reduced their weight, which is a satisfactory result in a
      clinical setting. The drop-out rate and the reasons for dropping out could give a
      clue in which direction the diagnostics and analysis of the subject's individual
      needs in health care should be directed.

PMID- 16801743
TI  - Thin-ideal internalization, body dissatisfaction and symptoms of eating disorders
      in Croatian adolescent girls.
AB  - The aim of this investigation was to study the relationship between unhealthy
      eating habits and behaviors, perception and acceptance of societal standards
      regarding thinness, body dissatisfaction, and family and peer pressure to be
      thin. One hundred and twentythree high school girls from Rijeka (Croatia) were
      surveyed using Eating Attitudes Test (EAT- 26), Sociocultural Attitudes Towards
      Appearance Questionnaire (SATAQ), Body Esteem Questionnaire for Adolescents and
      Adults (BES), and Scale of perceived pressure to be thin from family and peers.
      The results of path analyses showed that social pressure from family and peers,
      experience of weight-related teasing and criticism by family members, contributed
      to development of eating disturbance. The acceptance of social standards related
      to appearance, contributed to onset of disturbed eating habits. Weight
      satisfaction alone influences the development of some eating disorder symptoms,
      but it is also a mediator of higher body mass index (BMI) and internalization of
      societal appearance standards. Girls with higher BMI, who accepted societal
      standards of thin-ideal, perceived major social pressure to be thin through
      direct and persuasive comments designed to establish the importance of dieting,
      and probably develop eating disturbed habits, or some symptoms of anorexia (AN)
      or bulimia nervosa (BN).

PMID- 16801744
TI  - Severity of bulimic symptoms is the best predictor of interference on an
      emotional Stroop paradigm.
AB  - OBJECTIVE: The goal of the current study was to further investigate whether an
      emotional Stroop effect exists among patients with bulimia nervosa. METHOD:
      Performances of 30 female controls, 30 females with subclinical eating disordered
      symptoms, and 30 females diagnosed with bulimia nervosa were compared on an
      emotional Stroop color naming task using stimuli separated into three areas of
      concern (eating, weight, and shape words). RESULTS: Results indicated that
      overall the three groups differed significantly on the emotional Stroop task,
      with the interference latency for disorder salient words progressively increasing
      as the severity of bulimic symptoms increased. Severity of bulimic symptoms was
      the best predictor of interference on the emotional Stroop paradigm. DISCUSSION:
      Results provide further evidence that interference on the emotional Stroop is
      uniquely related to the symptoms of bulimia nervosa and bear credence to the
      possibility of its use as an additional tool in the diagnosis of bulimia nervosa.

PMID- 16801745
TI  - Eating disorder traits in obese children and adolescents.
AB  - The aim of the present study was to investigate the prevalence of eating disorder
      (ED) traits among obese children and adolescents. The Swedish version of the
      Eating Disorder Inventory for Children, consisting of 11 subscales, was
      administered to 150 obese patients during an extensive investigation of causes
      and risk factors in obesity at the Karolinska University Hospital at Huddinge.
      Patients aged 17-18 years (N=24) had a mean body mass index (BMI) of 40.7, SD
      5.31, and patients aged 8-16 (N=126) had a mean body mass index standard
      deviation score (BMI SDS) of 6.18, SD 1.69. These patients were compared with 201
      girls with a diagnosed ED from the COEAT project and with a control group of
      schoolchildren. The comparison between obese girls and boys showed that
      adolescent obese girls scored higher than obese boys on Drive for Thinness,
      Bulimia and Body Dissatisfaction. They also scored higher on Ineffectiveness,
      Interoceptive Awareness and Impulse Regulation. Obese girls were close to the
      girls with an ED on six of the subscales. Obese boys had a lower score of
      Asceticism than boys in the control group. The conclusion is that psychological
      traits associated with disordered eating appear among obese patients,
      particularly among the girls. However, these patients rarely satisfy any
      diagnostic criteria for ED during childhood or adolescence. Since obesity
      treatment currently assumes rational behavior, i.e. no EDs, it is important to
      discover ED traits at an early age in order to adapt treatment accordingly.

PMID- 16801747
TI  - [Management of serious bacterial infections: general considerations].
AB  - Many efforts have been made in the recent years to improve the prognosis of
      severe bacterial infections by reducing the risk of treating the patients
      inadequately. The reasons responsible for inadequate treatment have been
      intensively studied and antibiotic resistance has been identified as one of the
      main risks. Currently different strategies are considered to optimize antibiotic
      therapy, such as the adoption of local guidelines, de-escalation, rotation and
      association therapies. Each appears to prove efficacy in the containment of
      resistance and improvement of outcome; however, further studies, continuous
      monitoring of the epidemiology of severe infections and antibiotic resistance,
      and finally, availability of new drugs are needed. It is the authors' opinion
      that, despite the importance of guidelines for the optimal treatment and most
      appropriate management of severe infections, closer collaboration should be
      established between the medical staff in the wards and IDS, who can bridge the
      gap between the guidelines and the individual needs of the patient, thereby
      improving the decision-making process. The IDS, as consultant in different
      medical and surgical wards and as a member of the Infectious Diseases Control
      local Committees, can interact at different levels and can improve the management
      of severe bacterial infections.

PMID- 16801746
TI  - Relationship between spiritual well-being and binge eating in college females.
AB  - The aim of this study was to examine the relationship of spiritual well-being in
      college female non-binge, objective binge and binge-trait eaters. Therefore, this
      study aimed to measure spiritual well-being in non-binge, objective binge and
      partial/full-syndrome binge eating disorder college females. Survey research was
      conducted using a randomized sample of 809 female students. The sample was
      categorized into three binge eating categories: nonbinge, objective binge, and
      binge eating trait. Chi-Squares and Analysis of Variance determined binge eating
      group differences on demographics, global spiritual well-being, religious well
      being, and existential well-being. Significant differences were found among
      groups for global spiritual well-being (p< or = 0.000), religious well-being (p<
      or = 0.000), and existential well-being (p< or = 0.000). Higher levels of binge
      eating severity were associated with lower global spiritual and existential well
      being scores. On measures of religious well-being, significant differences
      existed between the non-binge and the binge eating trait groups. The results
      suggest that spiritual well-being and especially existential well-being may be
      indirectly associated with the severity of binge eating.

PMID- 16801748
TI  - [Guidelines for treatment of pneumonia in intensive care units].
AB  - Patients affected by pneumonia can be admitted in Intensive Care Units (ICUs)
      independently by the setting where the infection has been acquired (community,
      hospital, long-term care facilities); even more frequently pneumonia can develop
      in patients already hospitalized in ICU especially in those requiring mechanical
      ventilation for different reasons. Within the severe community acquired pneumonia
      requiring admission in ICU, the most frequently responsible micro-organisms are
      mainly represented by Streptococcus pneumoniae, but also by Legionella and
      Haemophilus. Pseudomonas aeruginona, anyway, cannot be excluded. The most recent
      Canadian and American guidelines for treatment of the above mentioned infections
      suggest the use of a combination therapy with beta-lactams (ceftriaxone,
      cefotaxime, ampicillin/sulbactam, piperacillin/tazobactam) and a new generation
      macrolide or respiratory fluoroquinolone. In case of allergy to beta-lactams, the
      association fluoroquinolone-clindamycin should be preferred. Whenever a
      Pseudomonas etiology is suspected because of the presence of risk factors such as
      COPD, cystic fibrosis, bronchiectasis, previous and/or frequent therapies with
      antibiotics and/or steroids, the same guidelines suggest the use of an anti
      pseudomonas beta-lactam (such as piperacillin/tazobactam, carbapenems, cefepime)
      associated with an anti-pseudomonas fluoroquinolone (high doses ciprofloxacin).
      An anti-pseudomonas beta-lactam plus an aminoglycoside or aminoglicosyde plus
      fluoroquinolone can be an alternative. Early onset Hospital Acquired Pneumonia
      (HAP) and early onset Ventilator Associated Pneumonia (VAP) in patients without
      risk factors for multi-resistant etiological agents are generally sustained by S.
      pneumoniae, H. influenzae, methicillin-susceptible Staphylocccus aureus e Gram
      negative enteric rods. These infections can be treated with one of the following
      antibiotics: ceftriaxone or fluoroquinolones (moxifloxacin or ciprofloxacin or
      levofloxacin) or ampicillin/sulbactam or ertapenem. Late onset VAP and HAP in
      patients with risk factors for multi-resistant, by contrast, should be treated
      with a combination therapy: in case of defined or suspected P. aeruginosa,
      Klebsiella pneumoniae (ESbL+), Acinetobacter sp etiology, it is required the use
      of an anti-pseudomonas cephalosporin or an anti-pseudomonas carbapenem or b
      lactam + beta-lactamase inhibitor associated with an anti-pseudomonas
      fluoroquinolone or an aminoglicoside. The possible presence of MRSA or Legionella
      pneumophila suggests the use of anti-Gram positive antibiotics such as
      glycopeptides or linezolid. These quidelines confirm the role of ciprofloxacin
      combined with beta-lactams whenever P. aeruginosa, Klebsiella pneumoniae (ESbL+),
      Acinetobacter sp. etiology is suspected.

PMID- 16801749
TI  - [Antibiotic treatment of intra-abdominal and post-surgical infections].
AB  - During the last years we observed a significant decrease of the mortality
      following the intra-abdominal infections thanks the improvement of surgical
      techniques and because of the improved approach of antibiotic treatments. The
      antibiotic therapy for the treatment of intra-abdominal infections greatly varies
      according to the infection severity. It is, in fact, possible to distinguish the
      intra-abdominal infections in three different categories. Mild infections should
      be treated promptly with surgical drainage and a short term therapy with a wide
      range antibiotic including anaerobes (ampicillin/sulbactam, cefoxitin). Mild
      moderate infections which are largely the most frequent in the clinical practice
      should be also treated with a single drug which include anaerobes in its
      spectrum. Finally severe infections require a more aggressive therapeutic
      approach with a combination treatment covering anaerobes (clyndamicin,
      metronidazole), Gram negative rods (ciprofloxacin, aminoglycosides) and Gram
      positive cocci (penicillins, cephalosporins) including MRSA (glycopetides) and/or
      VRE (linezolid). By the surgical point of view the control of intra-abdominal
      infections can require different procedures such as laparatomy, relaparotomy or
      less frequently laparostomy (totally or partially open abdomen). A strong synergy
      between the surgical procedures and antibiotic therapy represents the best way to
      approach and resolve even the most severe intra-abdominal infections.

PMID- 16801752
TI  - The Sauve-Kapandji procedure.

PMID- 16801750
TI  - Wound healing: an overview.
AB  - Understanding wound healing today involves much more than simply stating that
      there are three phases: inflammation, proliferation, and maturation. Wound
      healing is a complex series of reactions and interactions among cells and
      "mediators." Each year, new mediators are discovered and our understanding of
      inflammatory mediators and cellular interactions grows. This article will attempt
      to provide a concise overview on wound healing and wound management.

PMID- 16801753
TI  - Osteotomy for phalangeal malunion.

PMID- 16801755
TI  - Subfascial anterior transposition: a modified method for the treatment of cubital
      tunnel syndrome (CuTS).

PMID- 16801754
TI  - Treatment of syndactyly.

PMID- 16801756
TI  - Surgical treatment of dystrophic epidermolysis bullosa of the hand.

PMID- 16801757
TI  - Arthroscopic excision of dorsal wrist Ganglia.

PMID- 16801758
TI  - Resection of the distal ulna from a volar approach: Darrach revisited!

PMID- 16801760
TI  - "Custom-made" toe transfer for partial thumb amputation.

PMID- 16801759
TI  - New method in the treatment of mallet fracture.

PMID- 16801761
TI  - Postoperative management following thumb reconstruction.

PMID- 16801765
TI  - Postpartum depression.

PMID- 16801763
TI  - The Hospital as Sanctuary. An Arab nurse who cared for Israel's stricken prime
      minister.

PMID- 16801766
TI  - The eyes of the pediatric nurse.

PMID- 16801768
TI  - New Orleans redux.

PMID- 16801769
TI  - After the earthquake.

PMID- 16801770
TI  - Long hours.

PMID- 16801771
TI  - Cognitive changes in child cancer survivors.

PMID- 16801780
TI  - NCSBN 'Vision Paper' ignites controversy. Second licensure exam proposed;
      clinical nurse specialists excluded from advanced practice model.

PMID- 16801782
TI  - The Medicare prescription drug program. It's off to a confusing and expensive
      start.

PMID- 16801783
TI  - The increasing risk of Salmonella infections. Food industry practices, inadequate
      regulation, and antimicrobial resistance heighten concerns.

PMID- 16801784
TI  - Promises to keep. A 'routine' organ harvesting and a family's request.

PMID- 16801785
TI  - Can the use of LPNs alleviate the nursing shortage? Yes, the authors say, but the
      issues--involving recruitment, education, and scope of practice--are complex.
AB  - OVERVIEW: LPNs may be able to help fill some of the gaps caused by the nursing
      shortage, but little research has been conducted on the demographic
      characteristics of LPNs, their education and scope of practice, and the demand
      for their services, all of which vary from state to state. In 2002 and 2003, the
      authors conducted a comprehensive national study, Supply, Demand, and Use of
      Licensed Practical Nurses, and have summarized that study's findings in this
      article. They found that RNs and LPNs are similar in age and tend to have similar
      numbers of children, but that racial and ethnic minorities, particularly African
      Americans, and those who are single, widowed, divorced, or separated are better
      represented among LPNs. Expanding LPN educational programs might draw more people
      into nursing. Some LPNs would like to become RNs, so expanding LPN-to-RN "ladder"
      programs could also be beneficial. LPNs can't replace RNs entirely, but they
      could perform much of the work now performed by RNs. While long-term care
      facilities already depend heavily on LPNs, hospitals could benefit from employing
      more LPNs. The authors make several specific policy recommendations to improve
      the education and employment of LPNs.

PMID- 16801789
TI  - Trauma and intraabdominal hypertension. To prevent potentially lethal effects,
      monitor intraabdominal pressure.

PMID- 16801790
TI  - Mother-to-child transmission of HIV in the United States. Many HIV-infected women
      are now planning to have children. What are the risks to mother and infant?
AB  - OVERVIEW: With the rise in the number of HIV-infected women of childbearing age
      in the United States, nurses are increasingly likely to be caring for such women.
      Although the exact mechanism of mother-to-child HIV transmission is unknown,
      experts believe that it can occur during any of three stages: before birth by
      microtransfusion of maternal blood across the placenta, during labor and delivery
      by exposure to maternal cervicovaginal secretions and blood, and after birth
      through breastfeeding. Treating pregnant women with highly active antiretroviral
      therapy dramatically reduces the risk of such transmission, but little is known
      about long-term effects of such therapy on the children. This article reviews the
      literature on the risk of mother-to-child HIV transmission in the United States
      and the factors that influence that risk, details current practice
      recommendations, and discusses implications for nursing.

PMID- 16801792
TI  - Pain Control. A call to action to protect range orders. A consensus statement
      supports this important nursing responsibility.

PMID- 16801794
TI  - Nightingale nurses return. Nurse activists make the tobacco industry their
      target.

PMID- 16801800
TI  - Certification and magnet hospitals. Will certification advance your career and
      improve patient outcomes?

PMID- 16801801
TI  - Staying Power? Retaining mature RNs in the workforce.

PMID- 16801803
TI  - Pugilist nurse. She answers to a different bell.

PMID- 16801804
TI  - Handwashing. Going back to basics in infection control.

PMID- 16801805
TI  - The DAVES (Disfunzione Asintomatica VEntricolare Sinistra) study by the Italian
      Society of Cardiovascular Echography: rationale and design.
AB  - BACKGROUND: Diagnosis of heart failure (HF) is based on clinical signs,
      instrumental findings and response to treatment. The recent classification of the
      European Society of Cardiology identifies early stages of ventricular dysfunction
      not associated with symptoms of HF (Stage A-B). However, only few data are
      available on the prevalence and prognostic value of asymptomatic left ventricular
      dysfunction. METHODS: The SIEC (Societa Italiana di Ecografia Cardiovascolare -
      Italian Society of Cardiovascular Echography) has planned a national multicenter
      observational study aimed to assess: (1) the prevalence of left ventricular (LV)
      systolic and diastolic dysfunction in asymptomatic subjects without a history of
      HF (transversal phase); (2) the relationship between cardiovascular risk factors
      and LV asymptomatic dysfunction; (3) the relationship between comorbidities and
      LV asymptomatic dysfunction; and (4) the incidence of cardiac events at follow-up
      (longitudinal phase). Data from 75 echocardiographic laboratories were recorded,
      merged, and analyzed using a dedicated software. CURRENT STATUS: Recruitment
      started in June 2003 and closed in February 2004. Overall, 16 099 patients (men,
      8496; women, 7603; male: female ratio, 1.11) have been screened and 6679 (men,
      3504; women, 3175; male: female ratio, 1.10) were enrolled. The follow-up is
      currently ongoing.

PMID- 16801806
TI  - A medical therapy for aortic valve sclerosis and aortic valve stenosis? Rationale
      of the ASSIST study (Asymptomatic aortic Sclerosis/Stenosis: Influence of
      STatins): a large, observational, prospective, multicenter study of the Italian
      Society of Cardiovascular Echography.
AB  - Progression of sclerosis and stenosis is substantially unpredictable in the
      individual patient: in some cases it is very slow, in others it is accelerated.
      In addition, different patterns of progression (linear and non-linear) are
      possible. It has been suggested that the aortic valve lesion can be considered a
      form within the spectrum of the same atherosclerotic disease. In this context it
      seemed reasonable to hypothesize that targeted medical therapy could retard the
      progression of the disease. In particular HMG-CoA reductase inhibitors (statins)
      and angiotensin-converting enzyme inhibitors have been tested. The first
      experimental and clinical studies are now available, even though they are not
      conclusive to date. Large, prospective, randomized trials are ideally needed, but
      they are quite difficult, if not even impossible, to realize in practice. The
      ASSIST study (Asymptomatic aortic Sclerosis/Stenosis: Influence of STatins) of
      the Italian Society of Cardiovascular Echography aims to create a large,
      prospective, observational investigation, involving many centers of
      echocardiography and thousands of patients, in order to provide from the real
      clinical world at least some of the answers to this unsolved question.

PMID- 16801807
TI  - Stress echocardiography: refining the diagnosis of coronary artery disease.

PMID- 16801808
TI  - Coronary flow reserve evaluation in stress-echocardiography laboratory.
AB  - The assessment of coronary flow reserve by transthoracic echocardiography has
      recently been introduced into clinical practice with good results for the
      diagnosis of left anterior descending artery disease and fairly promising results
      for posterior descending coronary artery disease. By looking at what is behind
      wall motion, we may realize a sonographer's dream and, in particular, the
      addition of coronary flow reserve to regional wall motion analysis allows us to
      have - in the same sitting - high specificity (regional wall motion) and a highly
      sensitive (coronary flow reserve) diagnostic marker, with an improvement in
      overall diagnostic accuracy. Coronary flow reserve evaluation may shift the
      balance of stress choice in favor of vasodilators, which are easier to perform
      with dual imaging than dobutamine or exercise coronary flow reserve evaluation
      and may shift the choice in favor of dipyridamole or adenosine stress tests,
      which are also easier to perform with dual imaging than those using dobutamine or
      exercise. Lastly, it adds quantitative support to the exquisitely qualitative
      assessment of wall motion analysis, thereby facilitating the communication of
      stress echo results to the cardiological world outside the echo laboratory.

PMID- 16801809
TI  - Potential clinical perspectives of Doppler myocardial imaging and strain rate
      imaging during stress echocardiography.
AB  - Stress echocardiography has become a common non-invasive test in patients with
      chest pain and known or suspected coronary artery disease, but, as with exercise
      electrocardiography, it shows several major limitations. Analysis of gray-scale
      images based on subjective visual interpretation of wall motion and thickening
      has considerable variability even among experts. Doppler myocardial imaging and
      strain rate imaging echocardiography provides additional information in
      comparison with conventional echocardiography. These techniques provide
      quantification of regional wall motion at rest and during stress. Quantification
      of both systolic and diastolic myocardial function by either Doppler myocardial
      imaging or strain rate imaging mapping during dobutamine stress test has been
      shown to be a feasible, accurate, non-invasive tool that should be considered to
      be a sensitive alternative to the present echocardiographic and scintigraphic
      imaging techniques for stress tests. Time consuming off-line analysis of color
      images is required in the present state of technology. However, these non
      invasive techniques are rapidly evolving and expanding. Further refinements in
      signal processing and quantitative analysis are likely in the near future.

PMID- 16801810
TI  - New technologies applied to stress echocardiography: myocardial contrast
      echocardiography.
AB  - The development of new echocardiographic contrast agents that can be injected
      intravenously and can opacify left-sided cardiac chambers has offered a
      contribution in the field of stress-echocardiography for two main reasons: (1)
      the improvement of visualization of the endocardial border and thus facilitating
      recognition of wall motion abnormalities during pharmacological stress or
      physical exercise; and (2) the obtaining of information on myocardial perfusion
      during stress examinations. This review will consider: (1) the improvement of
      diagnostic accuracy during pharmacological stress or physical exercise obtained
      with the administration of echo-contrast agents; (2) the results of major studies
      for comparison of the myocardial contrast echocardiography technique versus
      single-photon emission computed tomography (SPECT) and coronary angiography; (3)
      the added value for studying perfusion other than wall motion analysis during
      stress echo; and (4) the advantages and limitations of different stress
      modalities. New multicenter studies should now definitively clarify the choice of
      the best contrast agents and create protocols for myocardial contrast
      echocardiography using different methods of image acquisition in order to unify
      the diagnostic process before a 'label approved' for perfusion of contrast
      echocardiographic agents. Finally, caution should be considered when contrast
      agents are used in the acute phase of myocardial infarction or ischemia.

PMID- 16801811
TI  - Echocardiography in atrial fibrillation.
AB  - Atrial fibrillation is the most commonly encountered sustained arrhythmia.
      Echocardiography has augmented the knowledge about etiology and complications of
      atrial fibrillation. Transthoracic echocardiography allows rapid, safe and
      comprehensive assessment of cardiac structure and function, and is recommended
      for all subjects with atrial fibrillation. The use of transesophageal
      echocardiography has contributed to a better understanding of the thromboembolic
      risk in patients with atrial fibrillation, especially in the setting of
      electrical cardioversion. Several investigators have demonstrated the feasibility
      and safety profile of early cardioversion with short-term anticoagulation in
      patients with atrial fibrillation and a transesophageal echocardiography negative
      for atrial thrombi. More recently, transesophageal and intracardiac
      echocardiography have been employed in patients with atrial fibrillation to
      monitor percutaneous procedures such as pulmonary veins radiofrequency ablation
      or left atrial appendage obliteration. In this review the available
      echocardiographic imaging modalities and their specific role in the evaluation
      and management in atrial fibrillation are described.

PMID- 16801812
TI  - Antithrombotic therapy in atrial fibrillation: beyond the AFFIRM study.
AB  - In the last few decades several clinical studies evaluated the efficacy and
      safety of different strategies for antithrombotic prophylaxis to prevent
      thromboembolic events in patients with atrial fibrillation (AF). Nowadays, a
      frequently debated point is related to the high embolic risk deriving from the
      asymptomatic and symptomatic AF recurrence after cardioversion or in paroxysmal
      AF, especially in patients with a large number of prolonged episodes of AF. In
      fact, after the recent AFFIRM and RACE trials, patients after successful
      cardioversion at risk for thromboembolism could also need lifelong
      anticoagulation. Considering this, should we anticoagulate all patients with
      clinical risk factors for thromboembolism with a single episode of AF, without
      considering the hemorrhagic risk? Based on recent trials, it is reasonable to
      hypothesize that long AF recurrences (> 48 h), both symptomatic and asymptomatic,
      are present mostly (if not exclusively) in patients with structural left atrial
      appendage (LAA) dysfunction and remodeling. Conversely, AF recurrences in
      patients without LAA dysfunction and remodeling, could be too short to allow
      thrombi formation in the LAA, and the anticoagulation could also be avoided. Once
      other clinical and echocardiographic determinants of stroke have been excluded,
      the LAA velocity could select patients with a normal appendage function at low
      embolic risk who could benefit from anti-aggregation and patients with
      irreversible appendage dysfunction, at high embolic risk, who need lifelong
      anticoagulation.

PMID- 16801813
TI  - Functional mitral regurgitation in heart failure.
AB  - Mitral regurgitation commonly occurs in patients with heart failure. Systolic
      dysfunction is the hallmark of dilated cardiomyopathy. Mitral functional
      regurgitation is mitral incompetence in the absence of intrinsic lesions of the
      mitral valve apparatus. Echocardiography can make a major contribution to the
      diagnosis of cardiomyopathies. A more careful anatomic and hemodynamic evaluation
      of mitral regurgitation mechanisms is possible with spectral Doppler, color
      Doppler, three-dimensional echocardiography and transesophageal echocardiography.
      Functional mitral regurgitation is due to the incomplete closure of mitral
      leaflets and is based on alterations of mitral annulus, left ventricular
      dimensions, function and geometry, left atrial dimensions and function. Knowledge
      of the mechanisms of mitral regurgitation helps us to gain an insight into
      therapeutic interventions that modify the mechanistic factors. Medical therapy
      reduces the tethering forces and also augments transmitral pressure; surgical
      approaches can modify geometric relationships in the left ventricular chamber and
      resynchronization therapy can improve co-ordinated timing of mechanical
      activation of papillary muscles.

PMID- 16801814
TI  - Clinical and hemodynamic implications of supra-annular implant of biological
      aortic valves.
AB  - The use of stented bioprostheses in elderly patients with degenerative aortic
      stenosis, despite being desirable, raises concerns about the harmful effects of
      residual obstruction to left ventricular outflow. To overcome this limitation new
      stented and stentless bioprostheses have been designed for supra-annular implant.
      However, the actual hemodynamic advantage of supra-annular implant over the intra
      annular one remains incompletely understood. This review focuses on the geometry
      of biological valve prostheses designed for supra-annular implant and its
      implications for the echocardiographic assessment of valve hemodynamics.
      Available data about the hemodynamic performance of these valves implanted in the
      supra-annular position in comparison with the usual intra-annular implant are
      also reviewed. Other issues related to biological heart valve performance, such
      as biomaterials, tissue mechanics, durability, and clinical outcome are not
      addressed in this review.

PMID- 16801815
TI  - Echocardiography in the diagnosis and management of pericardial disease.
AB  - This review covers the role of echocardiography in the diagnosis and management
      of the main pericardial disorders. The sensitivity of echocardiography in
      detecting pericardial fluid is very high and this technique allows the detection
      of effusion as well as the definition of the size of effusion (small, moderate
      and severe). The evaluation of the pericardial sac should be carefully performed
      through all the echocardiographic windows, differentiating diffuse from loculated
      (regional) effusions. Several echocardiographic and Doppler signs allow an
      accurate diagnosis of cardiac tamponade. The role of echocardiography is
      extremely important in atypical clinical presentation such as in patients in the
      postoperative period after cardiac surgery. Moreover, drainage of the effusion is
      mandatory in the presence of cardiac tamponade and in this regard echo-guided
      pericardiocentesis is the gold-standard method. Finally this review covers the
      echocardiographic diagnosis of pericardial cysts and masses and constrictive
      pericarditis.

PMID- 16801816
TI  - Echocardiographic estimation of pulmonary pressures.
AB  - Cardiac ultrasound plays a pivotal role in assessing pulmonary artery pressures.
      Estimation of right atrial pressure can be derived from the dimensions and
      respiratory variation of the inferior vena cava and Doppler modalities provide an
      accurate and comprehensive evaluation of right ventricular and pulmonary artery
      pressures. Peak pulmonary artery pressure can be calculated from continuous wave
      Doppler sampling of the tricuspid regurgitant jet, while pulsed wave Doppler
      sampling of the pulmonary regurgitant jet allows evaluation of mean and diastolic
      pulmonary artery pressures. In patients with tricuspid regurgitation that is
      either absent or not adequately detectable by Doppler method, Doppler right
      ventricular outflow tract investigation can be helpful. Recent data indicate that
      analysis of right ventricular function using myocardial Doppler echocardiography
      may also provide new insights for the non-invasive estimation of pulmonary artery
      pressures. In particular, right ventricular isovolumic relaxation time measured
      by myocardial Doppler echocardiography at the tricuspid annulus may provide an
      alternative method for estimating pulmonary artery pressure, especially in
      patients with tricuspid regurgitation not detectable or spectral Doppler not
      properly interpretable.

PMID- 16801817
TI  - Carotid intima-media thickness.
AB  - In advanced countries the incidence of cardiovascular diseases is constantly
      increasing. During the last century many resources were employed to investigate
      atherosclerosis in relation to the main risk factors and to modification of
      lifestyles. Technologies have been developed to identify atherosclerosis in the
      sub-clinical phase. Measurement of the carotid intima-media thickness (IMT) by B
      mode ultrasound is a well-validated procedure to detect the early stages of
      atherosclerosis and to track progression of atherosclerosis whereas other
      techniques have limited utility because of their invasive nature or limited
      sensitivity and reproducibility. In comparison with angiography, B-mode
      ultrasound has greater sensitivity for detecting early atherosclerosis and
      plaques at risk of rupture. IMT is associated with the severity of
      atherosclerosis in different vascular districts and has been measured in several
      clinical studies in order to assess the influence of risk factors, therapies and
      diet. It is also validated for drug evaluation. In spite of this evidence IMT
      measurement is not routinely performed in patients with high and middle levels of
      risk for cardiovascular diseases. Scientific societies and specifically those
      involved in ultrasonography should promote wider recognition of the diagnostic
      power of ultrasonic IMT by emphasizing the low costs and low risk of use of the
      instruments and its major contribution to knowledge, evaluation and monitoring of
      the progression of atherosclerosis.

PMID- 16801818
TI  - Echocardiographic evaluation of coronary artery fistula connecting the right
      coronary artery to the coronary sinus: a case report.
AB  - Coronary artery fistula is a rare incidental finding during routine cardiac
      catheterization. It is usually congenital but it may also be a consequence of
      chest trauma or iatrogenic procedures. Patients may be asymptomatic or experience
      signs and symptoms of myocardial ischemia. In this article we report a casual
      echocardiographic finding of a coronary artery anomaly in an asymptomatic patient
      who underwent successful surgical closure and remained well several years after
      the procedure.

PMID- 16801819
TI  - A rare case of isolated left ventricular non-compaction. Importance of image
      technology and disease awareness for a correct diagnosis.
AB  - In 1999 a 50-year-old man with sustained monomorphic ventricular tachycardia came
      to our institution for investigation using fundamental echocardiographic imaging.
      A diagnosis of hypertrophic cardiomyopathy with dilatation and apical thrombus
      was made. In 2003, a new echocardiographic machine equipped with second harmonic
      imaging modality became available and after a second investigation the diagnosis
      was changed to isolated left ventricular non-compaction. The echocardiogram
      showed hypertrabeculations involving not only the mid-septum but also the basal
      septum (anterior and posterior) and a thin epicardial layer without the thickened
      endocardial component.

PMID- 16801820
TI  - Improved delineation of morphological features of arrhythmogenic right
      ventricular cardiomyopathy with the use of contrast-enhanced echocardiography.
AB  - A case of an already diagnosed arrhythmogenic right ventricular cardiomyopathy in
      which the use of contrast improved the echocardiographic characterization of
      morphologic abnormalities of the right ventricle is reported.

PMID- 16801821
TI  - Refusal versus reluctance.

PMID- 16801822
TI  - Fixed high-dose electroconvulsive therapy in the elderly with depression: a
      double-blind, randomized comparison of efficacy and tolerability between
      unilateral and bilateral electrode placement.
AB  - OBJECTIVE: To evaluate efficacy and tolerability of unilateral (RUL) and
      bilateral (BL) electroconvulsive therapy (ECT) in the elderly with depression.
      METHODS: Thirty-nine elderly inpatients with major depression referred to ECT
      were randomized into RUL or BL ECT, using high, fixed electrical doses. Cognition
      and depression severity were assessed before, during, and 1 month after
      treatment. Adverse effects were assessed after each session. RESULTS: Remission
      rates for RUL ECT (88.2%) and BL ECT (68.2%) were similar (P = 0.25). Reduction
      rates of depressive symptoms were also similar. There were no serious adverse
      events. There were more adverse effects in the BL ECT group (P = 0.05). BL ECT
      showed more short-term cognitive impairment, whereas improvements in
      neuropsychological scores were seen in both groups. CONCLUSION: In elderly
      depressive subjects, high-dose RUL ECT is as effective as BL ECT yet produces
      less adverse effects and less cognitive impairment.

PMID- 16801823
TI  - Determinants of seizure threshold of electroconvulsive therapy in Chinese.
AB  - OBJECTIVES: Debates continue whether dose-titration, formula-based or fixed
      dosage method should be used during ECT. Regardless of the dosing method used,
      the range and the determinants of seizure threshold in different ethnic groups
      are useful clinical information. METHOD: Seizure threshold was quantified at the
      first ECT session using standardized dose titration and anesthetic protocols in
      165 Chinese patients. One-hundred and five patients were treated with bilateral
      ECT and 60 with unilateral ECT. RESULTS: The mean seizure threshold was 95.9 mC
      (range = 32-403 mC). The mean and range of seizure threshold for bilateral ECT
      were 115.1 mC and 48-403 mC, for unilateral ECT, the mean and range were 62.1 mC
      and 32-192 mC. Stepwise regression analysis showed that electrode placement and
      age were the two most important predictors of seizure threshold and accounted for
      32 and 20% of its variance respectively. Of lesser significance greater body mass
      index and concurrent use of antiepileptic were associated with higher seizure
      threshold. Unlike previous Western studies, we showed that gender had no
      significant relationship with seizure threshold for the total sample and
      unilateral ECT while for bilateral ECT interpretation is limited by the higher
      starting dose in men. CONCLUSION: Our finding added to the database on ECT in
      different ethnic groups and would be useful for the clinical practice of ECT in
      Chinese.

PMID- 16801824
TI  - Ketamine appears associated with better word recall than etomidate after a course
      of 6 electroconvulsive therapies.
AB  - Ten patients treated with electroconvulsive therapy (ECT) for depressive illness
      received anesthesia with either etomidate or ketamine. Three patients received
      both etomidate and ketamine anesthesia for ECT during separate episodes of
      depression. Patients anesthetized with ketamine for ECT had significantly less
      impairment of short-term memory function than did patients who received ECT with
      etomidate anesthesia. All patients who received both anesthetics for ECT during 2
      different episodes had less memory loss during ECT with ketamine than with
      etomidate. These results show the importance of studying the effects of all
      anesthetic agents used during ECT on cognitive functions. The results imply that
      the effect of ECT on memory may be largely caused by effects mediated by
      glutamate at N-methyl-d-aspartate receptors and suggest that N-methyl-d-aspartate
      antagonists may offer protection from memory dysfunction during ECT.

PMID- 16801825
TI  - Memory, attention, and executive functions before and after sine and pulse wave
      electroconvulsive therapies for treatment-resistant major depression.
AB  - OBJECTIVE: Studies of the cognitive effects of electroconvulsive therapy (ECT)
      have resulted in controversial findings up to now, partly because researchers and
      reviewers have not always made a clear distinction among various aspects of
      cognition and because there are many parameters involved in the administration of
      ECT that have a potential impact on cognition. The present study focused on the
      impact of sine and pulse waveforms on anterograde memory and nonmemory cognitive
      functions. METHODS: We assigned 18 patients with unipolar major depression or
      bipolar I or II disorder, most recent episode depressed, to receive sine wave or
      pulse wave ECT and assessed their cognitive function before and after ECT, using
      a neuropsychologic test battery that measured anterograde memory, attention, and
      executive functions. Outcomes were measured, on average, 8.2 days after the last
      ECT session. RESULTS: Both waveforms were equally effective in alleviating
      depression. Those who received sine wave ECT showed statistically significant
      deterioration in attention and executive tasks, such as the Stroop test, which
      measures selective attention (P = 0.02), and the dual task, which taps divided
      attention (P = 0.01). On the other hand, those who received pulse wave ECT
      improved to a significant degree in certain memory tasks, such as visual memory
      (P = 0.01) and general memory (P = 0.01) of the Wechsler Memory Scale-Revised
      (WMS-R), as well as in the dual task (P = 0.01). The between-group comparison
      revealed robust superiority of the pulse wave over the sine wave in terms of the
      dual task (P = 0.004). CONCLUSIONS: Anterograde memory improved to a
      statistically significant or nonsignificant degree at 1 week post-ECT in
      comparison with pre-ECT regardless of waveforms. Attention/executive functions
      tended to deteriorate with sine wave ECT but improved with pulse wave ECT.

PMID- 16801826
TI  - Should electroconvulsive therapy be an early consideration for suicidal patients?
AB  - INTRODUCTION: This article describes a quality management project undertaken for
      the purpose of ensuring that the most appropriate patients were being selected
      for electroconvulsive therapy (ECT) at an 80-bed, state-operated, civil
      psychiatric facility for the seriously mentally ill. METHOD: Thirty mentally ill
      patients, including patients with comorbid substance abuse diagnoses, were
      treated with ECT. Pre-ECT and post-ECT scores on the 24-item Brief Psychiatric
      Rating Scale (BPRS-24) were compared with admission and discharge BPRS-24 scores
      of a control group treated with psychotropic medication. RESULTS: ECT-treated
      patients demonstrated greater improvement in BPRS scores during a shorter period
      than did non-ECT-treated patients. Furthermore, the greatest improvement was seen
      in the areas of depression and expressed suicidal intent. An unanticipated result
      was that patients with comorbid substance abuse diagnoses treated with ECT showed
      the most improvement in these areas. CONCLUSION: ECT was shown to be particularly
      useful in the treatment of suicidally inclined depressed patients, suggesting
      that ECT should be an early consideration for suicidal patients.

PMID- 16801827
TI  - Patterns of psychotropic medication use among patients with severe depression
      referred for electroconvulsive therapy: data from the Consortium for Research on
      Electroconvulsive Therapy.
AB  - Most studies of trends in antidepressant pharmacotherapy have focused on
      relatively mildly ill, nonpyschotic outpatients. In this report, we provide
      detailed information on psychotropic use among patients with unipolar depression
      participating in a large, multisite electroconculsive therapy (ECT) study.
      Adequacy of antidepressant medication trials was assessed with the Antidepressant
      Treatment History Form. Among patients with nonpsychotic depression, 27% (60/220)
      had not had an adequate trial of an antidepressant before ECT, and 63% (139/220)
      had had at least one inadequate trial. Surprisingly, 33% (79/243) of nonpsychotic
      patients had been prescribed an antipsychotic. Among patients with psychotic
      depression, 95% (101/106) had not been given an adequate combination of an
      antidepressant and antipsychotic agent, mostly due to low doses of the latter
      class. Among all patients in the trial, 61% (213/352) had been prescribed at
      least one benzodiazepine, and only 7% (24/352) had been given a lithium
      augmentation trial. Use of hypnotic agents and anticonvulsants was common. In
      conclusion, patients with severe depression referred for ECT with a unipolar
      depressive episode have high rates of psychotropic usage, much of which is
      inadequate.

PMID- 16801828
TI  - Blood glucose before and after ECT treatments in Type 2 diabetic patients.
AB  - Electroconvulsive therapy (ECT) is often performed for patients with psychiatric
      disorders who also have diabetes mellitus. Some research has suggested that the
      course of ECT treatments does not have a consistent effect on blood glucose, but
      little data exist to inform the clinician about the effects of individual ECT
      treatments on blood glucose. In this study, 18 patients with type 2 diabetes
      mellitus were treated with ECT for severe depressive illness. For each patient, a
      fingerstick blood glucose was routinely obtained before and approximately 20
      minutes after each ECT treatment. We found a mean rise of blood glucose after
      each treatment of approximately 9%, similar to the mean rise of blood glucose
      among nondiabetic patients undergoing ECT found in a previous study. There were
      no cases of clinically significant rise or fall in blood glucose. We provide
      recommendations for management of diabetics during ECT.

PMID- 16801829
TI  - Electroconvulsive therapy: predictors and trends in utilization from 1976 to
      2000.
AB  - BACKGROUND: Use of electroconvulsive therapy (ECT) may have changed during the
      last decades due to advances in psychopharmacology and organizational changes of
      psychiatric care. OBJECTIVES: To identify predictors for receiving ECT for the
      first time and to describe temporal trends in ECT utilization. METHODS: A
      register-based case-control study. The sample included 2010 cases treated with
      ECT between 1976 and 2000 and 148,284 controls. RESULTS: Predictors for receiving
      first ECT were unipolar affective disorders, long admissions, and no previous
      admissions. Significantly fewer patients with bipolar and schizoaffective
      disorders received the treatment in 2000 compared with 1976. CONCLUSIONS:
      Unipolar affective disorders, long duration of admissions, and no history of
      previous admissions are strong predictors of receiving first ECT. Despite a
      decrease in available inpatient beds, the treatment is used in 5.5% of
      admissions, and during the last 15 years of the study period, ECT utilization has
      been remarkably stable.

PMID- 16801830
TI  - Knowledge and attitudes toward electroconvulsive therapy among health care
      professionals and students.
AB  - Widespread variations in electroconvulsive therapy (ECT) prescription between and
      within countries have led many researchers to study professionals' attitudes to
      the procedure. A questionnaire looking at knowledge and attitudes was
      administered to 593 medical and nursing students, psychiatrists and anesthetists,
      and theater and psychiatric nurses. Respondents were based in 2 Irish cities,
      Dublin and Cork. Poorer knowledge of ECT was found in the nursing group, and this
      included psychiatric nurses: a third overestimate ECT mortality, most did not
      know if it caused permanent brain damage, and only 1 psychiatric nurse (2.9%)
      expressed positive attitudes to its use. Nursing students had significantly lower
      knowledge and more negative attitudes than medical students, and exposure to the
      procedure of ECT failed to improve their attitudes. The strongest predictor of
      better knowledge and more positive ECT attitudes was membership of the medical
      group. There were direct associations between better knowledge and more positive
      attitudes in the medical group but not among the nursing group. Low ECT knowledge
      among psychiatric nurses has implications in obtaining patients' valid consent.
      Our failure to link exposure to ECT to better nursing attitudes is discussed
      along with other educational lessons.

PMID- 16801831
TI  - Combined use of ECT with duloxetine and olanzapine: a case report.
AB  - A 38-year-old woman with medication-resistant major depression and posttraumatic
      stress disorder was treated with electroconvulsive therapy (ECT) concurrent with
      a duloxetine-olanzapine combination. The treatment resulted in complete
      resolution of major depression without any complications. This case report
      suggests that treatment with the combination of duloxetine and olanzapine
      concurrently with ECT was found safe and uncomplicated. The literature on the
      combined use of antidepressants and ECT is briefly reviewed.

PMID- 16801832
TI  - Combined use of lamotrigine and electroconvulsive therapy in bipolar depression:
      a case series.
AB  - OBJECTIVE: Lamotrigine and electroconvulsive therapy (ECT) are both safe and
      effective treatments for bipolar depression. Concerns exist that anticonvulsants
      may interfere with seizure expression during ECT or may exacerbate cognitive side
      effects, potentially affecting clinical response. This report examines the
      clinical use of concurrent ECT and lamotrigine for acute bipolar depression and
      the transition to maintenance therapy. METHODS: Nine patients with acute bipolar
      depression were simultaneously treated with a course of ECT while titrating
      lamotrigine for maintenance therapy. We compared mean stimulus intensity, mean
      seizure duration, and mean time to orientation after treatment for each patient
      during treatment with their highest and lowest lamotrigine dose. RESULTS: All 9
      patients were treated to remission. From the lowest daily dose to the highest
      daily dose, mean increase in lamotrigine was 102.8 mg. Clinically adequate
      seizures were obtained in each patient. Lamotrigine had minimal effect on each
      measured ECT parameter. The interval between ECT treatments was spaced to a mean
      of 15.2 days. The treatment combination was well tolerated, with no serious
      adverse events, no rashes, and no worsening of cognitive side effects.
      CONCLUSIONS: Concurrent use of lamotrigine with ECT in bipolar depression seems
      safe, did not interfere with routine ECT practice, and allowed for transition to
      maintenance pharmacotherapy.

PMID- 16801833
TI  - Electroconvulsive therapy after coil embolization of cerebral aneurysm: a case
      report and literature review.
AB  - We report a case of an uneventful course after electroconvulsive therapy (ECT) of
      a patient who had undergone coil embolization for an intracranial aneurysm 37
      days earlier. There have been no reports until now of ECT after coil
      embolization. According to histopathologic examinations, it takes approximately 2
      weeks after coil embolization for the aneurysm to become fixed. The ECT can be a
      therapeutic option even in patients with a previous history of coil embolization,
      as long as it is performed under proper anesthetic management.

PMID- 16801834
TI  - Ischemic stroke after electroconvulsive therapy.
AB  - Stroke is an exceptionally rare complication of electroconvulsive therapy since
      modern anesthesia and appropriate medical screening were instituted in the 1950s.
      Postictal focal neurological deficits mimicking stroke are common, but the advent
      of acute stroke therapies has made the differentiation of these from true
      cerebrovascular events critical. We present the first case report of ischemic
      stroke after electroconvulsive therapy with radiographic confirmation.

PMID- 16801835
TI  - Gastric rupture after electroconvulsive therapy.
AB  - We report on a rare complication, gastric rupture, which developed during
      electroconvulsive therapy (ECT) under general anesthesia. The patient developed
      symptoms of gastric rupture immediately after recovery from the first ECT
      session. An x-ray confirmed the clinical diagnosis, and an emergency laparotomy
      was conducted. The patient recovered without further complications. We review the
      literature and discuss ECT and potential risk factors relevant to the
      pathophysiology of gastric rupture. Furthermore, recommendations are proposed for
      clinical management.

PMID- 16801836
TI  - Cortical blindness associated with electroconvulsive therapy.
AB  - BACKGROUND: Neurological syndromes arising in the context of electroconvulsive
      therapy (ECT) have rarely been reported in literature. METHODS: We report an
      adult man who received ECT during a manic episode and who developed prolonged
      confusion and transient (1 day) bilateral loss of vision immediately after the
      eighth treatment. RESULTS: Except for the blindness and the patient's lack of
      awareness of the symptom, the neurological examination was within normal limits.
      No abnormality was evident on brain computed tomographic scan. These findings
      suggest the diagnosis of cortical blindness. The patient was able to see normally
      when he awoke the next morning. He had complete amnesia for the events of the
      previous day. CONCLUSION: Transient cortical blindness is probably a very rare
      adverse effect of ECT. The findings are discussed in the context of visual
      impairment associated with epileptic seizures.

PMID- 16801837
TI  - Awareness under anesthesia during electroconvulsive therapy treatment.
AB  - Awareness under general anesthesia is an infrequent phenomenon during which
      patients become cognizant of some or all events during surgery or any procedure
      conducted under anesthesia. Awareness experiences can frighten patients and
      impact their memories in ways that can leave emotional and psychological problems
      that, over time, may develop into posttraumatic stress disorder. Inadequate
      anesthesia has been implicated in the causation of awareness under anesthesia. We
      report first case of patient gaining awareness while under anesthesia undergoing
      electroconvulsive therapy treatment. The case reported here would suggest that
      clinicians administering electroconvulsive therapy should be alert to the
      possibility of awareness during anesthesia and take appropriate measures to
      maintain professional conduct and adjust anesthetic medication dose to avoid
      reoccurrence.

PMID- 16801838
TI  - Vomiting of liquid corticosteroids in children with asthma.
AB  - BACKGROUND: Oral corticosteroids are an essential part of the management of
      children with acute asthma exacerbations. Vomiting is a frequently cited problem
      attributed to oral corticosteroids. A new formulation of prednisolone, Orapred,
      claims to have improved palatability that may decrease the incidence of vomiting.
      OBJECTIVE: To compare the incidence of vomiting and taste between patients who
      are given the generic preparation of prednisolone with those given Orapred.
      DESIGN/METHODS: A randomized, double blind clinical trial was conducted at a
      tertiary care children s hospital emergency department. Children age 2 to 10
      years presenting with acute asthma exacerbation were eligible. Patients with
      allergy to prednisolone, corticosteroid use within 2 weeks, history of vomiting
      in the last 24 hours, requirement for vascular access, and preference for other
      forms of corticosteroid were excluded. Enrolled patients were randomized and
      given either generic prednisolone (15 mg/5 ml) or Orapred (15 mg/5 ml). In
      children 6 years or older, a taste score was obtained using a 5 point hedonic
      face scale (1 = bad to 5 = great). After the administration, patients were
      observed for 30 minutes for vomiting. The Mann-Whitney U test was used to compare
      the median taste score between the two study groups. Relative risk (RR) of
      vomiting was calculated. Other confidence intervals were calculated when
      appropriate. RESULTS: During the study period, 211 eligible children were
      enrolled, of whom 23 were excluded. Of the remaining 188 subjects, 96 received
      generic prednisolone and 92 received Orapred. All baseline characteristics were
      similar in both groups. In the generic prednisolone group, 17 (17.7%) children
      vomited compared with 5 (5.4%) in the Orapred group (RR = 3.26, 95% CI, 1.25,
      8.47). Taste scores were obtained from 18 children in the generic prednisolone
      group and from 19 children in the Orapred group. The median taste score was 2 for
      the generic prednisolone group and 4 for the Orapred group (Delta = -2.0, 95% CI,
      -3.0, -1.0) (P = 0.0001). CONCLUSIONS: In our study population, Orapred was
      associated with a significant less incidence of vomiting and better taste score
      compared to the generic prednisolone.

PMID- 16801839
TI  - Risk of pediatric back-over injuries in residential driveways by vehicle type.
AB  - OBJECTIVE: Research suggests that children experience driveway back-over injuries
      at a significant rate and the severity of the resulting injuries differ by type
      of vehicle. Yet, no US study attempted to quantify "back-over risk" for classes
      of vehicles because of the difficulties with determining exposure. Using vehicle
      registration information, we set out to estimate the relative risk of driveway
      back-over injuries to children by type of vehicle. METHODS: Driveway back-over
      events were identified from state police reports and medical records from the
      state level 1 pediatric trauma center and compared with vehicle registration
      information to estimate injury incidence for 4 classes of vehicles (passenger
      cars, trucks, sport utility vehicles, and minivans) over 6 years in the state of
      Utah. RESULTS: Reported driveway back-over injuries represent an incidence of
      7.09 per 100,000 children (<10 years old) per year. Overall, passenger cars
      account for 1.62 injuries per 100,000 registered vehicles. Compared with
      passenger cars, children were 53% more likely to be injured by a truck (P = 0.01)
      and 2.4 times more likely to be injured by a minivan (P < 0.001). Among children
      transported to a trauma center, admission (P = 0.01) and need for surgery (P =
      0.03) were greater among children backed over by trucks, sport utility vehicles,
      and minivans compared with passenger cars. CONCLUSIONS: Findings suggest that
      when assessing driveway back-over injuries, larger high-profile vehicles are
      associated with a higher incidence and severity of injuries when compared with
      injuries resulting from passenger cars.

PMID- 16801840
TI  - Adverse events in pediatric ketamine sedations with or without morphine
      pretreatment.
AB  - OBJECTIVE: To assess outcomes between 2 groups of patients receiving ketamine for
      procedural sedations in our pediatric emergency department. Our hypothesis is
      that there is no difference in the number of adverse events in ketamine sedations
      with and without morphine pretreatment. METHODS: This was a retrospective cohort
      study of all ketamine sedation records over 15 months. The number and types of
      adverse events between patients with and without morphine pretreatment were
      examined. The numbers of adverse events in each group were compared using a z
      test. We also examined the possible influence of midazolam coadministration. P
      values were calculated using Pearson chi2 or Fisher exact tests. RESULTS: A set
      of 858 sedations were reviewed. Age, weight, and medication dosages were similar
      in each group. Twenty-one adverse events were recorded in the group of patients
      without morphine pretreatment. There were 13 adverse events in the group with
      morphine pretreatment. No significant differences were found for the number or
      types of events. There was no difference in the frequency of midazolam
      coadministration, Pearson chi2, P = 0.994, nor for the number of adverse events
      in each group, Fisher exact test, P = 0.465. The mean time from morphine
      administration to procedural sedation was 114.7 minutes. One adverse event
      occurred in the 15-minute or less time interval. CONCLUSIONS: We found no
      increase in the number of adverse events with morphine pretreatment in ketamine
      sedations for children. Prospective studies to validate these findings, including
      an effect of timing of analgesia administration, are warranted.

PMID- 16801841
TI  - Decrease in emergency department length of stay as a result of triage pulse
      oximetry.
AB  - OBJECTIVES: Many emergency departments do not perform pulse oximetry in triage,
      in spite of its potential for altering management decisions. We attempted to
      quantify the decrease in patient throughput time in a pediatric emergency
      department following the introduction of triage pulse oximetry. METHODS: One
      hundred fifty-nine bronchiolitis patients from 2004 served as the preintervention
      group, and were evaluated against 89 severity-matched postintervention
      bronchiolitis patients from 2005. Their mean lengths of ED stay were compared by
      a t test. RESULTS: The preintervention group had a mean length of stay of 4 hours
      and 59 minutes, and the postintervention group had a mean length of stay of 4
      hours and 9 minutes, which was significantly different (P = 0.03). The
      sensitivity of respiratory distress on the triage exam for predicting hypoxia was
      fair (74%). CONCLUSIONS: Institution of triage pulse oximetry significantly
      decreases ED throughput times. Clinical exam alone is not a replacement for
      measurement of oxygen saturation.

PMID- 16801842
TI  - Impact of a pediatric primary care office-based mock code program on physician
      and staff confidence to perform life-saving skills.
AB  - BACKGROUND: Previous studies have described that pediatric offices are ill
      prepared for medical emergencies. Pediatric "mock codes" have been utilized to
      increase the emergency preparedness of inpatient medical units for several
      decades. These practice drills have been shown to both increase practitioners'
      confidence and decrease anxiety during actual resuscitations. Although the use of
      mock codes is recommended in the outpatient setting, these benefits have yet to
      be demonstrated for office-based practitioners. OBJECTIVE: We conducted this
      study to determine whether mock codes performed in pediatric primary care offices
      increase practitioner confidence to perform life-saving skills. METHODS:
      Pediatric group practices participated in a clinical trial of an office-based, 2
      step, emergency preparedness training. First, physicians and staffs attended a 1
      hour didactic program which included staff education, office emergency protocols,
      emergency equipment and medications, and guidelines on instituting a mock code
      program. Second, each practice participated in a 10-15-minute mock code exercise.
      The drill was conducted by pediatric advanced life support instructors. After the
      code, a 30-minute feedback session was conducted which reviewed office
      coordination, individual skill performance, and approach to resuscitation. Each
      participating practice also received an infant manikin and a text complete with
      several mock codes scenarios written specifically for the pediatric primary care
      office. Evaluation of the intervention consisted of 2 components. (1) Pre- and
      postintervention completion of a self-administered survey assessed participants'
      comfort in emergency situations and confidence to perform specific life-saving
      skills, using an ordinal scale: 1 = "strongly agree" to 5 = "strongly disagree".
      (2) Practices were contacted by telephone 12 months after the training to
      determine whether they had implemented improvements in emergency preparedness,
      including instituting mock codes, preparing a written emergency protocol and
      purchasing new emergency equipment and medications. RESULTS: Eleven group
      pediatric practices participated, which were representative of urban, suburban,
      and rural offices in southwestern Pennsylvania. Ninety-seven of a total 164 (59%)
      physicians and staff members completed both pre- and postintervention surveys.
      Practitioner participants were analyzed in 2 groups. Group 1 consisted of
      physicians, nurse practitioners, and physician assistants; group 2 consisted of
      registered nurses, licensed practical nurses, and medical assistants. Comparison
      of pre- versus postintervention surveys in both of these groups revealed
      significant improvement in reported confidence to perform resuscitation skills
      that were included in the mock code after the training: airway positioning (group
      1, 67% vs. 94%, P < 0.001; group 2, 55% vs. 75%, P = 0.003), airway suctioning,
      (group 1, 64% vs. 88%, P = 0.005; group 2, 27% vs. 51%, P < 0.001), and bag-mask
      assisted ventilation (group 1, 82% vs. 91%, P = 0.003; group 2, 39% vs. 71%, P <
      0.001). In addition, group 1 reported more confidence in their ability to place
      an intraossesous line (24% vs. 39%, P = 0.003) and group 2 showed a significant
      increase in their confidence to administer oxygen (65% vs. 84%, P < 0.001). As a
      result of the mock code, 83% of all participants, both medical and nonmedical
      staffs, and 96% of physicians felt less anxious about medical emergencies in the
      office. Twelve months after the conclusion of the program, 18% of offices had
      conducted 1 or more mock codes, 64% of offices had written an emergency protocol,
      and 27% of offices had acquired essential resuscitation medications or equipment.
      CONCLUSIONS: The results of this study support the recommendation that mock codes
      should be performed in the pediatric primary care setting to improve practitioner
      confidence and decrease practitioner anxiety.

PMID- 16801843
TI  - Visit-level acuity and resource-based relative value unit utilization in a
      pediatric emergency department.
AB  - OBJECTIVE: There is currently limited data on the distribution of evaluation and
      management (E&M) codes and resource utilization in pediatric emergency
      departments. We sought to ascertain the following: (1) the distribution of visit
      level acuity among patients who sought care in our pediatric emergency department
      (PED); (2) mean relative value units per physician hour (RVUs/h) as a measure of
      health care provider productivity; (3) the extent of correlation between the mean
      number of patients seen per hour and RVUs/h; and (4) the difference in RVU's
      generated using observation codes versus a higher level E&M code for diagnoses
      that require an extended level of service. DESIGN/METHODS: The study was
      conducted at an urban tertiary level, university-affiliated PED in a freestanding
      children's hospital. After obtaining data from patient encounters during the
      period from January through December 2004, we calculated total RVUs by using 2004
      national Medicare data that pertained to facility coding, adjusted for data from
      Tennessee. We also reviewed the frequency of 3 diagnoses that usually require
      extended care to determine disposition (status asthmaticus [International
      Classification of Disease-9 Diagnosis Code 493.91], volume depletion [276.5], and
      sickle cell disease with crisis [282.62]). Utilizing a high-level E&M code
      (99285) and high-level, same day observation code (99236), we compared RVUs
      generated for each of the earlier said diagnoses. RESULTS: During the study
      period, 61,444 patient encounters occurred. Of the patients seen, 4678 (7.6%)
      were admitted. The most common E&M code used was 99283 (53.7%). The mean RVU's/h
      for pediatric emergency medicine physicians and for pediatricians (and nurse
      practitioners) were 4.36 and 3.08, respectively. There was high correlation
      between RVU's/h and the number of patients seen per hour (r = 0.85). The
      cumulative frequency of the 3 diagnoses that required extended care was 2602.
      Total RVUs generated when the high-level E&M code 99285 and the high-level
      observation code 99236 were used was 10,408 and 15,143, respectively.
      CONCLUSIONS: Our descriptive study provides PED benchmarking data on E&M code
      distribution and RVU utilization. RVU's/h may serve as a reliable measure of
      productivity. Although the use of observational codes in the PED requires
      additional documentation, their use for select diagnoses may appropriately
      reflect the level of service and have a favorable impact on the total number of
      RVU's generated.

PMID- 16801844
TI  - An unusual case of knee pain.
AB  - Osteomyelitis of the patella is a rare disease, which primarily affects the
      pediatric population. We present a case of hematogenous osteomyelitis of the
      patella with secondary development of septic arthritis of the knee. There is
      often a delay in diagnosis, as illustrated by our case report, due to the rarity
      of the condition and nonspecific presentation. There is usually no history of
      trauma. Focal tenderness over the patella is the most helpful clinical sign. A
      small joint effusion may be present which is usually sterile and reactionary due
      to inflammation of the patella. Treatment of osteomyelitis of the patella is
      similar to treatment of osteomyelitis in other areas. Function and range of
      motion of the knee usually returns to normal after completion of treatment. A
      delay in diagnosis may lead to progression of disease and complications such as
      septic arthritis of the knee.

PMID- 16801845
TI  - Multiple cardiac arrhythmias in a previously healthy child: a case of accidental
      digitalis intoxication?
AB  - We present a case of multiple arrhythmias in a 3-year-old child who was presented
      to the emergency department with emesis. Initial vital signs were significant for
      a heart rate from 40 to 60 beats per minute with stable blood pressure. An
      electrocardiogram showed complete atrioventricular block with a junctional escape
      rhythm of 40 to 55 bpm that subsequently progressed to atrial
      flutter/fibrillation and then to a junctional escape rhythm. She was given
      intravenous atropine, resulting in acceleration of the junctional rhythm. Sinus
      rhythm resumed with a prolonged PR interval a few hours later with normalization
      of the electrocardiogram the following day. Routine laboratory tests, toxicology
      screens, and tests for other cardiac medications in the home were negative.
      However, at 20 hours after presentation, her digoxin level was 2.9 ng/mL. Parents
      denied that the child had access to any digoxin-containing substances. This case
      illustrates that digoxin toxicity can manifest with multiple arrhythmias and that
      recognition of this can be very difficult, especially when there is no witness to
      ingestion. Clinicians should be suspicious for digoxin toxicity when a child
      presents with persistent emesis, altered level of consciousness, and
      bradyarrhythmias with or without hemodynamic instability.

PMID- 16801846
TI  - Syncope, seizure, or surprise? A teenager's school trip gone awry: case report of
      torsades de pointes and a review of long QT syndrome.

PMID- 16801847
TI  - Myocarditis presenting as gastritis in children.
AB  - Vomiting and abdominal pain are common pediatric complaints encountered by
      emergency physicians. The differential diagnosis of abdominal pain is extensive.
      Herein, we report 2 cases with fatal myocarditis who initially presented with
      abdominal pain and vomiting. Both cases were presented with abdominal pain,
      vomiting, and loose stools. On arrival at our emergency department, hypotension,
      tachycardia, and cyanotic extremities were found. Their serum troponin-I levels
      were elevated. The echocardiogram demonstrated poor left ventricular performance
      and a decreased ejection fraction. In both cases, an arrhythmia and a coma
      developed within hours and were shortly followed by death. The clinical
      presentations of acute myocarditis are variable, ranging from an initial mild
      discomfort to acute progressive heart failure, and at times, even death.
      Abdominal pain may be a manifestation of systemic disease, an extra-abdominal
      lesion, or myocarditis. Although myocarditis associated with abdominal pain or
      vomiting remains a diagnostic challenge to physicians, it should be considered in
      the differential diagnosis of children with gastritis and hypotension or who are
      refractory to rehydration therapy.

PMID- 16801848
TI  - Latex-induced anaphylactic reaction in a child with spina bifida.
AB  - Allergy to natural rubber latex presents a unique challenge in the emergency
      department. Latex allergy in children is most commonly identified in patients who
      have undergone multiple operations for neural tube defects or genitourinary
      anomalies. We report a life-threatening anaphylactic reaction to latex in a
      patient with spina bifida even with latex-free precautions.

PMID- 16801849
TI  - The dramatic change in the epidemiology of pediatric epiglottitis.
AB  - OBJECTIVE: To review the epidemiology of epiglottitis in a large children's
      hospital from 1995-2003 and to compare the findings with a previous report
      published 27 years previously from the same hospital. METHODS: Chart review.
      RESULTS: Two cases identified. Both children were 18 years old. Group F and group
      A streptococci were causative agents. CONCLUSIONS: Over the past 27 years, the
      admission rate for acute epiglottitis declined ten fold. Streptococci are
      becoming major pathogens in acute epiglottitis.

PMID- 16801850
TI  - Decontamination and the use of personal protective equipment.

PMID- 16801852
TI  - ECGs in the ED.

PMID- 16801853
TI  - Motor vehicle accident, loss of consciousness, and back pain.

PMID- 16801854
TI  - Not a basic case.

PMID- 16801857
TI  - Recurrent intracortical mass causing elbow pain.

PMID- 16801858
TI  - A slow growing mass on the back in a 63-year-old man.

PMID- 16801859
TI  - Forearm mass in an 11-year-old.

PMID- 16801860
TI  - Intraarticular knee mass in a 30-year-old woman.

PMID- 16801861
TI  - Importance of biopsy of new bone lesions in patients with previous carcinoma.
AB  - Development of destructive bone lesions in a patient with a history of visceral
      carcinoma may be assumed to be meta-static disease. However, this assumption may
      lead to inappropriate treatment. We prospectively enrolled 50 patients (54
      previous malignancies) from the South Australian Musculoskeletal Tumour Service
      with new metastases to bone after a previous diagnosis of localized visceral
      carcinoma. We performed biopsies on the new lesions and reviewed the patients'
      histories. The most common diagnosis was breast carcinoma (24 patients), followed
      by prostate (11 patients) carcinoma. The mean time between the first primary
      malignancy and the development of a bony lesion was 84 months (range, 30-83
      years). The longest latency was with breast carcinoma and the shortest was with
      lung carcinoma. The bone abnormality was a new tumor in nine patients (15%),
      necrotic tissue in two patients, and normal tissue in one patient. A new tumor
      was most likely in patients with breast carcinoma (five patients) or prostate
      carcinoma (three patients). The bone lesion was always the same malignancy in
      patients with a history of renal or lung carcinoma. Failure to do a biopsy would
      have resulted in serious treatment errors in two of the three patients who had
      new tumors develop. We recommend performing biopsies for new bone lesions,
      especially if breast carcinoma was the previous primary malignancy.

PMID- 16801862
TI  - Infiltrative MRI pattern and incomplete initial surgery compromise local control
      of myxofibrosarcoma.
AB  - Myxofibrosarcoma (MFS) has a high local failure rate of up to 79%. We conducted a
      retrospective analysis on all patients with the diagnosis of myxofibrosarcoma
      seen between 1990 and 2004 to assess whether improved imaging with MRI reduced
      local recurrence, increased survival, and whether radiotherapy following
      resection influenced outcome. Twenty-one patients were treated for MFS with a
      median followup of 52 months (range, 18-122). All patients were surgically
      treated, with 19 receiving limb-sparing surgery. All patients with high grade
      disease, positive margins, or a pre-referral procedure received radiation
      therapy. The local recurrence rate was 57% for patients with a prior outside
      procedure (8 of 14), while patients with no prior surgery had a rate of 14% (1 of
      7). Prior marginal excision and diffuse fascial spread on MRI predicted an
      increased local recurrence rate. The disease-free survival at 5 years was 43%
      (SE, 22%) for low-grade disease and 39% (SE, 18%) for high- grade disease.
      Magnetic resonance imaging observations suggest a unique pattern of diffuse
      spread along fascial planes that could be responsible for the high local
      recurrence. Radiation did not compensate for positive margins, nor did it reduce
      recurrence after negative margins. LEVEL OF EVIDENCE: Therapeutic study, level IV
      (case series).

PMID- 16801863
TI  - Knee arthritis in congenital short femur after Wagner lengthening.
AB  - Knee anomalies are common in patients with congenital short femurs who require
      lengthening to correct limb-length discrepancies. We retrospectively reviewed the
      incidence of knee arthritis and the factors influencing its occurrence after
      femoral lengthening using the Wagner method. Twenty-three patients with
      congenital short femurs treated with the Wagner method were followed up until
      skeletal maturity (minimum, 5 years postoperatively). The mean age of the
      patients at lengthening was 10.8 years (range, 8.4-14.5 years). The mean leg
      length discrepancy at the time of surgery was 9.7 cm (femur, 7.6 +/- 3.7 cm;
      tibia, 2.1 +/- 1.8 cm). Femoral lengthening (mean, 7.9 cm) was performed in 17
      patients. Femoral lengthening and tibial lengthening were performed
      simultaneously in six patents (mean, 11.8 cm). The mean age of the patients at
      the last followup was 16.8 years (range, 14-20.3 years). Eighteen patients had
      arthritis at followup. Nine patients had severe arthritis develop, seven of whom
      had knee instability preoperatively and temporary subluxation during the
      lengthening procedure. Seventy-eight percent of patients had arthritis develop in
      the knee after lower-limb lengthening using the Wagner method for congenital
      short femurs. Patients who had an unstable knee before surgery had temporary knee
      subluxation develop during the lengthening procedure, and patients who had
      simultaneous lengthening of the femur and tibia had a high association with
      degenerative arthritis changes in the knee.

PMID- 16801865
TI  - Therapeutic hypothermia for anoxic brain injury following cardiac arrest: a
      "cool" transition toward cardiopulmonary cerebral resuscitation.

PMID- 16801866
TI  - The spice of life: curcumin reduces the mortality associated with experimental
      sepsis.

PMID- 16801867
TI  - Dalteparin: only protective in hepatic ischemia-reperfusion or also capable of
      preventing injury in liver hyperperfusion syndrome?

PMID- 16801868
TI  - Blood avoidance for the critically ill: another blow to liberalism?

PMID- 16801869
TI  - Retention of critical care nurses: Important to the future of critical care.

PMID- 16801870
TI  - RIFLE criteria provide robust assessment of kidney dysfunction and correlate with
      hospital mortality.

PMID- 16801871
TI  - Cooling after cardiac arrest: have we reached the tipping point?

PMID- 16801872
TI  - Is measuring B-type natriuretic peptide in critically ill patients ever useful?

PMID- 16801873
TI  - Beyond sepsis: activated protein C and heat stroke.

PMID- 16801874
TI  - Sepsis and the BBB: brain injury, biomarkers, and the bedside.

PMID- 16801875
TI  - Blood pressure control after intracerebral hemorrhage: have we reached the
      target?

PMID- 16801876
TI  - Editorial response: evoked potentials can be used as a prognosis factor for
      awakening.

PMID- 16801878
TI  - Rat or human-based blood therapy in acute myocardial infarction?

PMID- 16801879
TI  - Selective decontamination of the digestive tract does not increase resistance in
      critically ill patients: evidence from randomized controlled trials.

PMID- 16801882
TI  - When failure to intubate is failure to oxygenate.

PMID- 16801883
TI  - Does the addition of glutamine to enteral feeds affect patient mortality?

PMID- 16801886
TI  - [Should we continue to publish clinical research in French?].

PMID- 16801887
TI  - Technical and functional results after laparoscopic rectopexy to the promontory
      for complete rectal prolapse. Prospective study in 54 consecutive patients.
AB  - INTRODUCTION: Laparoscopic rectopexy for complete rectal prolapse offers short
      term advantages compared with operations performed by laparotomy. The aim of this
      prospective study was to report technical and functional outcome after
      laparoscopic rectopexy to the promontory in consecutive patients operated on by a
      single surgeon. PATIENTS AND METHODS: From May 1996 to July 2004, 54 consecutive
      patients (47 women), median age 53 years (range: 16-84 years), underwent
      laparoscopic rectopexy to the promontory for complete rectal prolapse.
      Preoperative evaluation included physical examination, dynamic videoproctography
      and, in patients with constipation, colonic transit time (with radiopaque
      markers). Postoperative evaluation included the same examinations and a simple
      global quality-of-life questionnaire. RESULTS: Conversion to laparotomy was
      required for three patients during the learning curve. Median duration of
      operation was 157 minutes (range: 50-370). There was no mortality and morbidity
      was 5.5% (brachial plexus palsy in two patients and urinary tract infection in
      one). Median hospital stay was 3.5 days (range: 1-11). There were 4 recurrences
      (7.4%). Functional outcome at 12 months showed the presence of constipation in
      20.3% of patients (persistence in eight and de novo in three) and the presence of
      outlet obstruction in 25.9% of patients (persistence in six and de novo in
      eight). Anal continence improved in 72.4% of the 29 patients who complained of
      this symptom. The global quality-of-life questionnaire showed a satisfactory
      result in 96% of patients. CONCLUSION: Laparoscopic rectopexy to the promontory
      is a safe and efficient procedure to treat complete rectal prolapse; morbidity is
      low. Functional outcome is at least equivalent to that obtained with open
      procedures in terms of continence, constipation and outlet obstruction.

PMID- 16801888
TI  - Gastrointestinal endoscopes cleaned without detergent substance following an
      automated endoscope washer/disinfector dysfunction.
AB  - OBJECTIVE: To report cases of gastrointestinal endoscopies performed with
      endoscopes that were reprocessed without detergent substance during a period of
      dysfunction of the automated endoscope reprocessor (AER). METHOD: A dysfunction
      of the AER for the cycles requiring detergent substance was reported at the
      Grenoble University Hospital on March 2005. During this period, 72 patients had
      potentially been exposed to a contaminated endoscope. A recall procedure was
      organized and serologic tests (HIV, HCV, HBV) were performed 3 and 6 months after
      the AER incident. RESULTS: Within the 72 patients convened, 56 (77.8%) were seen
      in consultation and accepted the serologic screening. Finally, serologic
      screening was done for 59 patients (81.9%) and no seroconversion for HIV, HCV, or
      HBV was observed. The final attrition rate was 13 patients (18.1%). CONCLUSION:
      No viral infection was transmitted during the AER dysfunction. After this AER
      incident, the monitoring of the endoscopic procedures and the traceability of the
      cleaning process were both improved to prevent further incidents.

PMID- 16801889
TI  - Sacral neuromodulation in the treatment of severe anal incontinence. Forty
      consecutive cases treated in one institution.
AB  - INTRODUCTION: Sacral neuromodulation is a recognized therapeutic option in severe
      anal incontinence from neurogenic origins, when medical treatment has failed.
      METHODS: We report the results of this procedure applied in 40 consecutive
      patients operated on by a single surgeon from August 2001 to June 2004. Mean
      duration of incontinence was 5 years. There were 33 women and 7 men of mean age
      59 (range 29-89). All patients had had medical treatment, 26 had had
      physiotherapy and 9 had been previously operated on for that problem.
      Neuromodulation consisted in a temporary electrical stimulation test followed by
      implantation of a stimulator in case of efficacy. RESULTS: Twenty nine patients
      had a positive test and were implanted. Ten had a negative test and one is
      waiting for implantation. From the 29 patients, 23 had uneventful postoperative
      course. Incontinence score varied from 17 before neuromodulation to 6 after in
      the 24 patients who were improved. Mean resting pressure, mean maximum squeeze
      pressure and mean duration of squeeze pressure did not change from pre to
      postoperative period. CONCLUSION: Sacral neuromodulation is a safe and
      efficacious procedure in properly selected anal incontinent patients. However, we
      observed no correlation between clinical and manometric data.

PMID- 16801890
TI  - Applicability and efficacy of qualifying criteria for an appropriate use of
      diagnostic upper gastrointestinal endoscopy.
AB  - Appropriate indication for upper gastrointestinal endoscopy (UGE) may be
      facilitated by referring to qualifying criteria such as those devised by the
      European Panel (EPAGE) and French Experts (ANAES). This prospective study
      evaluates the applicability and efficacy of these criteria in clinical practice.
      PATIENTS AND METHODS: A total of 522 patients was included (55% inpatients, 57%
      male, mean age 55 years). Appropriateness of referral was evaluated using EPAGE
      and ANAES criteria sets by a single independent expert. RESULTS: EPAGE criteria
      were applicable in 71% of cases. Indications for UGE were appropriate,
      inappropriate and uncertain in 62%, 27% and 11% respectively; 74%, 16% and 10% of
      clinically significant lesions detected by UGE were disclosed in patients having
      appropriate, inappropriate and uncertain indications respectively. ANAES criteria
      were applicable in 81% of cases. Indications for UGE were appropriate in 74%,
      inappropriate in 26%; 76% and 24% of clinically significant lesions detected by
      UGE were disclosed in patients having appropriate and inappropriate indications
      respectively. Whatever the criteria set used, all cancers and most of the severe
      lesions were observed in patients with appropriate indications: those patients
      were more often in-patients and were significantly older than patients belonging
      to the inappropriate group. CONCLUSION: Reference to EPAGE and ANAES qualifying
      criteria facilitates patient selection for UGE. Final decision must however rely
      upon practitioner advice. ANAES criteria are significantly more often applicable
      than EPAGE ones. However EPAGE referential when applicable is more predictive of
      the UGE findings.

PMID- 16801892
TI  - [Botulinum toxin and chronic anal fissure].
AB  - Lateral internal sphincterotomy is widely used in the treatment of chronic anal
      fissure. However, it is associated with a high rate of irreversible incontinence.
      For this reason the botulinum toxin has become a medical means of reversible
      sphincterotomy. Indeed, this neurotoxin induces relaxation of the smooth internal
      anal sphincter lasting one to three months after one injection. We reviewed the
      published studies about the use of this technique in the management of chronic
      anal fissure. Healing occurred in more than 70% of fissures without irreversible
      incontinence. Although further studies are needed to determine the best
      modalities of administration, especially due to the remaining significant
      recurrence rate, this toxin may be a valuable treatment for chronic anal fissure
      in the future.

PMID- 16801891
TI  - [Descending perineum in women].
AB  - Physiopathological and clinical interpretation of the descending perineum as
      described by A. Parks in 1970 remains difficult. This review is based on the
      literature between 1966 and 2004. The observed symptoms are more often due to
      associated lesions. The descending perineum on X-ray is not always symptomatic.
      Colpocystography shows the descent of the perineum and pelvic disorders from the
      anterior and middle parts of the perineum whereas defecography seems to provide a
      better diagnosis of dyschesia due to posterior damage (such as rectocele or endo
      anal intussusception). The first step of treatment is reeducation and medical
      treatment because there is no consensus for surgical therapy. Soft sacrocolpopexy
      by the abdominal approach with three meshes, one under the bladder, one in front
      of and one behind the rectum can be proposed for complete descending perineum.
      Transanal rectal resection by staple could be useful when the descending perineum
      is only associated with a rectocele and/or an intra-anal intussusception.

PMID- 16801893
TI  - [What examinations should be performed before mucosectomy?].

PMID- 16801895
TI  - [Positron emission tomography (PET) in gastrointestinal cancer].

PMID- 16801894
TI  - [Colonography].

PMID- 16801896
TI  - [Functional exploration of esophageal reflux].

PMID- 16801897
TI  - Videocapsule investigation of small bowel.

PMID- 16801898
TI  - [Is there a risk to prescribe paracetamol at therapeutic doses in patients with
      acute or chronic liver disease?].

PMID- 16801899
TI  - Hepatitis E is an autochthonous disease in industrialized countries. Analysis of
      23 patients in South-West France over a 13-month period and comparison with
      hepatitis A.
AB  - OBJECTIVES: Hepatitis E virus (HEV) is responsible for acute hepatitis
      predominantly in developing countries. In Western Europe and in the US, cases of
      acute HEV infection are uncommon and occur primarily in travelers returning from
      endemic countries. The aim of this study was to describe patients with acute
      hepatitis E in South West France and compare them with patients with acute
      hepatitis A. METHODS: 23 consecutive patients over 13 months were analysed. Acute
      hepatitis E was diagnosed on the presence of specific serum antibodies or viral
      RNA detection in serum or stools. Real time PCR products from viraemic patients
      were sequenced. RESULTS: All the HEV sequences belonged to genotype 3. Two
      patients (8%) died during their hospital stay, both suffered from severe
      underlying disease. Only 3 patients (13%) had travelled outside of Europe, within
      3 months of the onset of disease. When compared to 23 patients with acute
      hepatitis A at the same hospital and during the same time frame, HEV-infected
      patients were older (54.4 +/- 16.6 vs 24.5 +/- 16.6, P<0.05), had lower ALT
      levels (55.4 X upper normal limit +/- 48.6 vs 107.8 X upper normal limit +/-
      82.8, P<0.05) and had lower incidence of recent travel outside of Europe (13% in
      the hepatitis E group vs 60% in the hepatitis A group, P<0.05). CONCLUSIONS:
      Hepatitis E can be considered an autochthonous infection in South West France.
      All strains sequenced were related to genotype III. When compared to hepatitis A,
      HEV-infected patients were older, had lower ALT levels and had a lower incidence
      of travel outside of Europe.

PMID- 16801901
TI  - [Problems with therapeutic acetaminophen use in excessive drinkers].

PMID- 16801900
TI  - Influence of acetaminophen at therapeutic doses on surrogate markers of severity
      of acute viral hepatitis.
AB  - OBJECTIVES: Data on the influence of acetaminophen intake on acute viral
      hepatitis is scarce, but it could play a role in the worsening of this disease.
      The aim of this study was to determine whether the intake of acetaminophen at
      therapeutic doses affects the severity of acute viral hepatitis. METHODS: This
      was a prospective study concerning 37 consecutive patients hospitalized for acute
      viral hepatitis. Acetaminophen consumption and time since last intake were
      assessed by a questionnaire. Parameters of severity were studied in comparison to
      time related serum concentrations of acetaminophen. RESULTS: Patients
      hospitalized for acute viral hepatitis (18 male, 19 female patients) had a mean
      age of 29.2 +/- 11.5 years. The causal virus was HAV (n=23), HBV (n=7) and other
      viruses (n=8). The mean cumulated dose of acetaminophen was 7.7 +/- 5.65 g. The
      daily dose did not exceed the therapeutic dosage and the mean was 1.95 +/- 0.81 g
      (1-3 g). Patients who received 7.5 g of acetaminophen or more had a lower
      prothrombin index 52.4 +/- 30.3% vs 74.2 +/- 17.2% (P=0.039), and a lower factor
      V 54.7 +/- 33.2% vs 83.3 +/- 19.6% (P=0.033). Prothrombin index and bilirubinemia
      were negatively correlated with time related plasma acetaminophen concentrations.
      CONCLUSIONS: The use of acetaminophen at therapeutic doses was associated with
      greater alterations of surrogate markers of the severity of acute viral hepatitis
      especially hepatitis A. This was related to cumulated dosages and correlated to
      the time related acetaminophen plasma concentrations. Acetaminophen use should be
      interrupted when acute hepatitis is suspected.

PMID- 16801902
TI  - [Digestive actinomycosis: three cases and review].
AB  - Actinomycosis is a chronic suppurative disease. It is caused by an anaerobic
      bacterium, generally Actinomyces israelii. Cervical and thoracic localizations
      are most frequent. Digestive actinomycosis is rare and can simulate cancer
      leading to resection. We report 3 cases of surgical abdominal actinomycosis.
      Localization was colic in 2 cases and hepatic in 1 case. The diagnosis of
      actinomycosis was made after resection in the 3 cases. The evolution was
      favourable under medical treatment. These observations illustrate the difficulty
      of diagnosing this rare and unrecognised disease which can be cured by long term
      penicillin therapy.

PMID- 16801903
TI  - [Subcutaneous emphysema, pneumomediastinum, pneumoperitoneum and
      retropneumoperitoneum following a colonoscopy with mucosectomy].
AB  - The occurrence of associated intraperitoneal and retroperitoneal colonic
      perforation is uncommon after colonoscopy. We report a case of this complication
      revealed by subcutaneous emphysema, pneumomediastinum, pneumoperitoneum and retro
      pneumoperitoneum after colonic mucosectomy.

PMID- 16801904
TI  - [Bleeding from rectal varices in a patient with severe decompensated cirrhosis:
      success of endoscopic band ligation. A case report and review of the literature].
AB  - In patients with cirrhosis, portal hypertension can be complicated by bleeding
      rectal varices. Treatment of bleeding rectal varices is not well established
      because clinical therapeutic trials are scarce in the literature and there are
      only a few case reports. In most cases, first line treatment is endoscopic (band
      ligation or sclerotherapy) and in case of failure or rebleeding, portosystemic
      shunts are the second line treatment. The indication of endoscopic treatment is
      not always easy in patients with cirrhosis and impaired liver function as well as
      major haemostatic problems. We report the case of a patient with severe
      decompensated cirrhosis and bleeding rectal varices who was successfully treated
      by endoscopic band ligation.

PMID- 16801905
TI  - Acute hepatitis C during the third trimester of pregnancy.
AB  - A pregnant woman presented at 32 weeks of amenorrhea with jaundice secondary to
      acute hepatitis C. Spontaneous delivery took place 3 days later. The infant's
      serum tested negative for C viral RNA 6 months after delivery. Treatment with
      high doses of interferon-alpha for a period of 4 weeks was begun 4 days after
      delivery. Although a virological response was noted at the end of the treatment,
      the hepatitis relapsed and progressed toward chronicity. Case reports of acute
      hepatitis C during pregnancy are very rare, as the methods used for the follow-up
      of pregnant women render the diagnosis of asymptomatic forms difficult. In one
      case, the acute hepatitis C was severe. The occurrence of acute hepatitis C
      during pregnancy seems to increase the risk of premature delivery, but not that
      of vertical transmission. Given the frequency of side effects, it seems
      preferable not to begin interferon treatment until after delivery.

PMID- 16801906
TI  - [Delayed recurrence of an endobiliary hepatocellular carcinoma without detectable
      intra-parenchymatous tumor].
AB  - Obstructive jaundice is uncommon in patients with hepatocellular carcinoma. It
      can be due to compression of the common bile duct by the liver tumor or by
      enlarged lymph node metastases in the porta hepatis. Obstructive jaundice can
      also be due to direct extension of hepatocellular carcinoma into the bile ducts
      with or without a detectable primary hepatic tumor. These particular
      hepatocellular carcinoma have been termed "icteric type hepatoma" by Lin et al.
      in 1975, who emphasized their poor prognosis. We report a similar case of
      endobiliary hepatoma without a detectable intraparenchymal hepatic tumor in a
      seventy year-old man. This case is unusual because of its positive evolution and
      late recurrence.

PMID- 16801907
TI  - [Major hemorrhage following colonic cold biopsies].

PMID- 16801908
TI  - [Imaging of polyps of the colon by PET Scan].

PMID- 16801909
TI  - Oxaliplatin-induced immune thrombocytopenia.

PMID- 16801910
TI  - [How to treat well differentiated endocrine carcinoma with a high proliferative
      index? A case of gastric endocrine carcinoma].

PMID- 16801911
TI  - [Acquired hemophilia and viral hepatitis B infection].

PMID- 16801912
TI  - Women in neuroscience: a numbers game.

PMID- 16801914
TI  - Fool me once, shame on me--fool me twice, blame the ACC.

PMID- 16801915
TI  - Fractalkine: moving from chemotaxis to neuroprotection.

PMID- 16801916
TI  - When is enough enough?

PMID- 16801917
TI  - The ebb and flow of attention in the human brain.

PMID- 16801918
TI  - Nitro-PDI incites toxic waste accumulation.

PMID- 16801919
TI  - Trailblazers of the cortex.

PMID- 16801923
TI  - Effect of obesity on posture and hip joint moments during a standing task, and
      trunk forward flexion motion.
AB  - OBJECTIVE: Effects of obesity on trunk forward flexion motion in sitting and
      standing, and postural adaptations and hip joint moment for a standing work task.
      DESIGN: Cross-sectional comparison of obese and normal weight groups. SUBJECTS:
      Ten obese subjects (waist girth 121.2+/-16.8 cm, body mass index (BMI) 38.9+/-6.6
      kg m(-2)) and 10 age- and height-matched normal weight subjects (waist girth
      79.6+/-6.4 cm, BMI 21.7+/-1.5 kg m(-2)). METHODS: Trunk motion during seated and
      standing forward flexion, and trunk posture, hip joint moment and hip-to-bench
      distance during a simulated standing work task were recorded. RESULTS: Forward
      flexion motion of the thoracic segment and thoracolumbar spine was decreased for
      the obese group with no change in pelvic segment and hip joint motion. Obese
      subjects showed a more flexed trunk posture and increased hip joint moment and
      hip-to-bench distance for a simulated standing work task. CONCLUSIONS: Decreased
      range of forward flexion motion, differing effects within the trunk, altered
      posture during a standing work task and concomitant increases in hip joint moment
      give insight into the aetiology of functional decrements and musculoskeletal pain
      seen in obesity.

PMID- 16801924
TI  - Perinatal overfeeding in rats results in increased levels of plasma leptin but
      unchanged cerebrospinal leptin in adulthood.
AB  - OBJECTIVE: To study the effect of perinatal programming and overfeeding on the
      hypothalamic control mechanisms of food intake in adult rats. DESIGN: Neonatal
      programming effects on body weight, food intake, central and peripheral leptin
      levels, hypothalamic neuropeptides, leptin receptors and central leptin
      responsiveness in adult rats. MEASUREMENTS: Plasma and cerebrospinal fluid (CSF)
      leptin levels were analyzed using radioimmunoassay. Neuropeptide mRNA levels were
      analyzed using in situ hybridization. Leptin receptor mRNA levels were analyzed
      using reverse transcriptase-polymerase chain reaction. RESULTS: Perinatally
      overfed rats growing up in small litters (SL) maintain their obese and
      hyperleptinemic phenotype in adulthood. However, leptin levels in CSF are
      abnormally low considering the plasmatic hyperleptinemia. In contrast to the
      already reported changes in perinatally overfed juvenile rats, perinatally
      overfed adult rats did not show any alteration in the expression of leptin
      receptor isoforms and evaluated neuropeptides. Moreover, SL adult rats showed a
      normal sensitivity regarding the inhibitory effect of intracerebroventricular
      leptin administration on food intake. CONCLUSION: Perinatal overfeeding does not
      induce alterations in either the anorectic response to central leptin
      administration or expression of leptin receptors and neuropeptides in adulthood.
      The leptin resistance to peripheral leptin in SL adult rats may be related to
      impaired leptin transport across the blood-brain barrier.

PMID- 16801925
TI  - beta-Adrenergic control of stearoyl-CoA desaturase 1 repression in relation to
      sympathoadrenal regulation of thermogenesis.
AB  - Mice lacking beta-adrenoceptors, which mediate the thermogenic effects of
      norepinephrine and epinephrine, show diminished thermogenesis and high
      susceptibility to obesity, whereas mice lacking stearoyl-CoA desaturase 1 (SCD1),
      which catalyzes the synthesis of monounsaturated fatty acids, show enhanced
      thermogenesis and high resistance to obesity. In testing whether beta-adrenergic
      control of thermogenesis might be mediated via repression of the SCD1 gene, we
      found that in mice lacking beta-adrenoceptors, the gene expression of SCD1 is
      elevated in liver, skeletal muscle and white adipose tissue. In none of these
      tissues/organs, however, could a link be found between increased sympathetic
      nervous system activity and diminished SCD1 gene expression when thermogenesis is
      increased in response to diet or cold, nor is the SCD1 transcript repressed by
      the administration of epinephrine. Taken together, these studies suggest that the
      elevated SCD1 transcript in tissues of mice lacking beta-adrenoceptors is not a
      direct effect of blunted beta-adrenergic signalling, and that beta-adrenergic
      control of SCD1 repression is unlikely to be a primary effector mechanism in
      sympathoadrenal regulation of thermogenesis. Whether approaches that target both
      SCD1 and molecular effectors of thermogenesis under beta-adrenergic control might
      be more effective than targeting SCD1 alone are potential avenues for future
      research in obesity management.

PMID- 16801926
TI  - The glucose clamp reveals an association between adiponectin gene polymorphisms
      and insulin sensitivity in obese subjects.
AB  - Results concerning the association of adiponectin gene polymorphisms (single
      nucleotide polymorphisms, SNPs) with obesity, type 2 diabetes (T2DM), metabolic
      disorders and insulin resistance have not lead to definite conclusions. The aim
      of our study was to investigate a possible association between the -11391G>A and 
      11377C>G SNPs of adiponectin gene and measure of insulin sensitivity evaluated by
      the hyperinsulinemic-euglycemic clamp in a group of 'uncomplicated' obese
      subjects (with no associated comorbidities) (n=99, mean age 35 years) with a
      history of obesity lasting at least 10 years. The study of uncomplicated obese
      subjects, free of possible confounding factors that could interfere with insulin
      sensitivity, such as pharmacological treatment, provides a good model to assess
      insulin sensitivity per se. We observed that subjects homozygous for the G allele
      at locus -11391 had lower M (mg/kg min)/fat-free mass (FFM) index and adiponectin
      levels compared to subjects with GA+AA genotypes (P=0.002 and P=0.03,
      respectively) and subjects carrying the -11377G variant had lower M (mg/kg
      min)/FFM index and adiponectin levels compared to noncarriers (P=0.003 and
      P=0.03, respectively). Our results imply that the two promoter SNPs, -11391G>A
      and -11377C>G, of the adiponectin gene are associated with a reduced insulin
      sensitivity evaluated by hyperinsulinemic-euglycemic clamp in obese subjects.

PMID- 16801927
TI  - Successful weight maintenance preserves lower levels of oxidized LDL achieved by
      weight reduction in obese men.
AB  - OBJECTIVE: We studied the association between weight maintenance, oxidized low
      density lipoprotein (ox-LDL) and other lipoproteins in obese men. METHODS: A 2
      month weight reduction phase (WRP) with a very-low-energy diet was followed by a
      6-month weight maintenance period and an unsupervised 2-year follow-up. Ninety
      men entered and 68 (76%) completed the study. Subjects were analyzed as one group
      and after division into two subgroups: 20 most successful men in maintaining the
      lost weight (subgroup 1) and the remaining (n=48) men (subgroup 2). Ox-LDL was
      measured by quantifying the amount of conjugated dienes in LDL particles.
      RESULTS: The mean (+/-s.d.) weight reduction at the end of the WRP (n=68) was 14%
      (confidence interval (CI) 12.9-14.7%, 14.5+/-4.2 kg, P<0.001). Ox-LDL decreased
      by 22% (CI 16.9-28.1, 12.3+/-15.4 micromol/l, P<0.001). At the end of the 2-year
      follow-up, the regain in weight from the end of the WRP was 11% (CI 9.0-12.4,
      9.6+/-6.2 kg, P<0.001). The regain in ox-LDL was 30% (CI 18.7-41.2, 8.2+/-15.4
      micromol/l, P<0.001). In subgroup 1 vs 2, the respective regains were 3% (CI 0.9
      4.2, 2.2+/-3.0 kg, P=0.006) vs 14% (CI 12.7-15.6, 12.9+/-4.0 kg, P<0.001)
      regarding weight and 9% (2.0+/-6.9 micromol/l, P=NS) vs 39% (CI 23.7-53.9, 11.2+/
      17.2 micromol/l, P</=0.001) in ox-LDL. CONCLUSION: The favorable changes seen in
      ox-LDL particles and serum lipids during weight reduction could be maintained by
      keeping the weight reduced, which may indicate decreased risk of atherosclerosis.
      But weight regain causes a resurge of ox-LDL.

PMID- 16801928
TI  - Regulation of ghrelin is related to estimated insulin sensitivity in obese
      children.
AB  - OBJECTIVE: To investigate whether ghrelin concentrations and their changes during
      weight loss in obese children are associated with parameters of glucose and
      insulin metabolism. DESIGN: Total plasma ghrelin, insulin and glucose were
      measured during oral glucose tolerance testing before and after diet-induced
      weight loss over 6 weeks. SETTING: In-patient rehabilitation program in a
      pediatric hospital. PARTICIPANTS: Twenty-three obese children (age 10-16 years)
      and 11 normal weight controls (age 10-15 years). OUTCOME MEASURES: Changes in
      ghrelin concentrations during weight loss and correlation analysis of changes in
      ghrelin and changes in parameters of glucose and insulin metabolism. After data
      collection, subgroup analysis of obese patients with high, medium and low
      estimated insulin sensitivity whole-body insulin sensitivity index (WBISI) was
      performed. RESULTS: Weight loss increased the area under the curve (AUC) of
      ghrelin by 26% (P<0.001). The increase in ghrelin AUC correlated significantly
      with improved estimated insulin sensitivity (WBISI) (r=0.69, P<0.001). The
      independent predicting effect of WBISI was confirmed in multivariate analysis. In
      children with low WBISI, ghrelin reached the level of control values after weight
      loss. In children with high WBISI, ghrelin increased markedly above control
      levels. CONCLUSIONS: Changes in ghrelin are independently associated with changes
      in glucose and insulin metabolism. The increase in plasma ghrelin above control
      levels was limited to obese children with high WBISI.

PMID- 16801929
TI  - Co-twin control designs for testing behavioral economic theories of child
      nutrition: methodological note.
AB  - OBJECTIVE: To illustrate the use and potential efficiency of the co-twin control
      design for testing behavioral economic theories of child nutrition. DESIGN: Co
      twin control design, in which participating twins ate an ad libitum lunch on two
      laboratory visits. At visit 1, child food choices were not reinforced. On visit
      2, twins were randomized to conditions such that one twin was reinforced for each
      fruit and vegetable serving consumed during lunch ('contingent') while his co
      twin was reinforced irrespective of food intake ('non-contingent'). SUBJECTS: Six
      male twins, 5 years old, from three monozygotic twin pairs. MEASUREMENTS: Ad
      libitum intake of total energy (kcals), fat (kcals), and fruits and vegetables
      (servings) from the protocol test meals on the two visits. RESULTS: Compared to
      twins receiving non-contingent reinforcement, twins receiving contingent
      reinforcement increased fruit and vegetable intake by 2.0 servings, reduced fat
      intake 106.3 kcals, and reduced total energy intake by 112.7 kcals. The relative
      efficiency of the co-twin control design compared to a conventional between
      groups design of unrelated children was most powerful for detecting 'substitution
      effects' (i.e., reduced total energy and fat intake) more so than for detecting
      increased fruit and vegetable intake. CONCLUSION: Genetically informative
      studies, including the co-twin control design, can provide conceptually elegant
      and efficient strategies for testing environmental theories of child nutrition
      and obesity.

PMID- 16801930
TI  - Putative contributors to the secular increase in obesity: exploring the roads
      less traveled.
AB  - OBJECTIVE: To investigate plausible contributors to the obesity epidemic beyond
      the two most commonly suggested factors, reduced physical activity and food
      marketing practices. DESIGN: A narrative review of data and published materials
      that provide evidence of the role of additional putative factors in contributing
      to the increasing prevalence of obesity. DATA: Information was drawn from
      ecological and epidemiological studies of humans, animal studies and studies
      addressing physiological mechanisms, when available. RESULTS: For at least 10
      putative additional explanations for the increased prevalence of obesity over the
      recent decades, we found supportive (although not conclusive) evidence that in
      many cases is as compelling as the evidence for more commonly discussed putative
      explanations. CONCLUSION: Undue attention has been devoted to reduced physical
      activity and food marketing practices as postulated causes for increases in the
      prevalence of obesity, leading to neglect of other plausible mechanisms and well
      intentioned, but potentially ill-founded proposals for reducing obesity rates.

PMID- 16801931
TI  - Some mathematical and technical issues in the measurement and interpretation of
      open-circuit indirect calorimetry in small animals.
AB  - Indirect calorimetry is increasingly used to investigate why compounds or genetic
      manipulations affect body weight or composition in small animals. This review
      introduces the principles of indirect (primarily open-circuit) calorimetry and
      explains some common misunderstandings. It is not widely understood that in open
      circuit systems in which carbon dioxide (CO2) is not removed from the air leaving
      the respiratory chamber, measurement of airflow out of the chamber and its oxygen
      (O2) content paradoxically allows a more reliable estimate of energy expenditure
      (EE) than of O2 consumption. If the CO2 content of the exiting air is also
      measured, both O2 consumption and CO2 production, and hence respiratory quotient
      (RQ), can be calculated. Respiratory quotient coupled with nitrogen excretion
      allows the calculation of the relative combustion of the macronutrients only if
      measurements are over a period where interconversions of macronutrients that
      alter their pool sizes can be ignored. Changes in rates of O2 consumption and CO2
      production are not instantly reflected in changes in the concentrations of O2 and
      CO2 in the air leaving the respiratory chamber. Consequently, unless air-flow is
      high and chamber size is small, or rates of change of O2 and CO2 concentrations
      are included in the calculations, maxima and minima are underestimated and will
      appear later than their real times. It is widely appreciated that bigger animals
      with more body tissue will expend more energy than smaller animals. A major issue
      is how to compare animals correcting for such differences in body size.
      Comparison of the EE or O2 consumption per gram body weight of lean and obese
      animals is misleading because tissues vary in their energy requirements or in how
      they influence EE in other ways. Moreover, the contribution of fat to EE is lower
      than that of lean tissue. Use of metabolic mass for normalisation, based on
      interspecific scaling exponents (0.75 or 0.66), is similarly flawed. It is best
      to use analysis of covariance to determine the relationship of EE to body mass or
      fat-free mass within each group, and then test whether this relationship differs
      between groups.

PMID- 16801932
TI  - Effects of level and degree of spinal cord injury on male orgasm.
AB  - DESIGN: Controlled, laboratory-based analysis. OBJECTIVE: To determine the impact
      of spinal cord injuries (SCIs) on the ability to achieve male orgasm. SETTING: US
      academic medical center. METHODS: A laboratory-based analysis of the ability of
      45 men with SCIs and 16 able-bodied control subjects to achieve orgasm coupled
      with a detailed neurologic examination, history and physical examination, and
      administration of the International Index of Erectile Function. RESULTS: Men with
      SCIs were less likely than controls to achieve orgasm. Mean latency to orgasm,
      blood pressure and heart rates at orgasm were not significantly different between
      controls and SCI subjects. Men with incomplete SCIs were more likely to achieve
      orgasm than those with complete SCIs. A disconnect was noted between the presence
      of orgasm and the presence of ejaculation. Men with complete lower motor neuron
      dysfunction affecting their sacral segments were less likely to achieve orgasm
      than men with any other patterns of SCI. CONCLUSION: These results document the
      ability of men with complete SCIs to achieve orgasm. Characteristics of orgasm in
      men with SCIs as compared to able-bodied subjects are similar. Although orgasm
      and ejaculation are more likely to occur together, a number of men with SCIs
      achieve orgasm without ejaculation. Further research should explore the
      possibility of retraining ejaculatory and orgasmic responses in men with SCIs.

PMID- 16801933
TI  - Ossification of the proximal thoracic ligamenta flava causing acute myelopathy in
      a Caucasian: case report and literature review.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVE: To illustrate that
      ossification of the proximal thoracic ligamenta flava can be a rare cause of
      acute myelopathy in a Caucasian patient and that timely surgery can lead to a
      good outcome. SETTING: Nottingham, UK. METHODS: Proximal multiple contiguous
      ossified thoracic ligamenta flava from T3/T4 to T5/T6 causing acute myelopathy
      was diagnosed in a Caucasian man based on history and examination followed by
      magnetic resonance imaging and computed tomography scanning. The literature is
      reviewed for all reported cases of ossified ligamenta flava causing myelopathy in
      Caucasians. RESULTS: Following prompt diagnosis and T3 to T5 laminectomies, our
      patient made near-complete neurological recovery over a 10-month period. This
      condition usually affects the lower thoracic spine. Although chronic and subacute
      myelopathy secondary to this circumstance has been reported in Caucasians, acute
      myelopathy has not been reported and proximal thoracic involvement has been
      reported twice. CONCLUSION: Ossification of the proximal thoracic ligamenta flava
      can be a rare cause of acute myelopathy in Caucasians. Prognosis following
      decompressive surgery is usually good.

PMID- 16801934
TI  - Effect of harness application and postural changes on cardiovascular parameters
      of individuals with spinal cord injury.
AB  - STUDY DESIGN: Prospective assessment of cardiovascular parameters in individuals
      with spinal cord injury (SCI) in response to harness application and postural
      changes including orthostatic stress. OBJECTIVE: To evaluate arterial blood
      pressure and heart rate (HR) with and without harness application during sitting,
      supine, and standing positions in able-bodied and SCI individuals. METHODS:
      Measurements were obtained in all SCI research participants (n=11) before a
      locomotor training intervention and compared to data with able-bodied individuals
      (n=9). During standing, all research participants wore a harness and were
      suspended by an overhead, pneumatic body weight support system. RESULTS: Resting
      arterial blood pressure and HR in individuals with cervical SCI were
      significantly lower during sitting than in thoracic SCI and able-bodied
      individuals (P<0.05). Orthostatic stress significantly decreased arterial blood
      pressure only in individuals with cervical SCI (P<0.05). Harness application had
      no effect on cardiovascular parameters in able-bodied individuals, whereas
      diastolic blood pressure was significantly increased in those with SCI.
      Orthostatic changes in cervical SCI when sitting were ameliorated by harness
      application. However, while standing with harness, individuals with cervical SCI
      still developed orthostatic hypotension. CONCLUSIONS: Level of injury to the
      spinal cord influences baseline cardiovascular parameters. Application of harness
      in individuals with SCI could alter baseline cardiovascular parameters and the
      response to orthostatic stress. This should be carefully considered when
      assessing effects of therapeutic interventions using body weight support in
      individuals with SCI.

PMID- 16801935
TI  - Phosphodiesterase inhibitors in the treatment of erectile dysfunction in spinal
      cord-injured men.
AB  - STUDY DESIGN: Open, before-after study. OBJECTIVE: To assess the efficacy and
      safety of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction
      (ED) in spinal cord-injured (SCI) patients. SETTING: Home- and clinic-based
      assessments in the outpatient department at the Centre Bouffard Vercelli, Cerbere
      France. METHODS: Clinic trials with Sildenafil (Viagra) on 120 patients,
      Tadalafil (Cialis) on 54 patients and Vardenafil (Levitra) on 66 patients were
      performed. Flexible doses of PDE5 inhibitors were given depending on efficacy and
      tolerability, from 50 to 100 mg for Sildenafil, and from 10 to 20 mg for
      Vardenafil and Tadalafil. Each trial was performed after a week's interval. The
      efficacy was self-assessed by the patients on a six-point quantitative scale
      assessment. The response to treatment was assessed at home in 90 patients (57
      patients on Sildenafil, 12 patients on Vardenafil and 21 patients on Tadalafil)
      using the International Index of Erectile Function (IIEF). RESULTS: In clinic
      trials, PDE5 inhibitors were effective (rigidity enough for penetration) in 85%
      of the patients on Sildenafil, 74% of the patients on Vardenafil and 72% of the
      patients on Tadalafil. The mean duration of erection was 34, 28 and 26 min,
      respectively. Adverse effects were mild, usually attenuated with continued
      dosing. More than 70% of the patients on Vardenafil and Tadalafil required higher
      doses of 20 mg, whereas 50 mg of Sildenafil was effective in 55% of the patients.
      Two-thirds of our patients on Tadalafil reported a duration of action longer than
      24 h. The presence of an upper motor neuron lesion was significantly associated
      with therapeutic success, lower motor neuron lesions and cauda equina patients
      were poor responders. Other variables such as completeness of lesion had no
      impact. In the follow-up visits, the IIEF global scores and three IIEF domains
      (erectile function, intercourse satisfaction and overall satisfaction) were
      significantly improved in all patients. Patients on Sildenafil showed a
      significant improvement of orgasmic function, ejaculation (Question 9) and orgasm
      (Question 10). CONCLUSION: Sildenafil, Vardenafil and Tadalafil are all effective
      and well-tolerated treatments for ED in SCI patients. Although no statistical
      analysis could be applied on these data, these results might indicate that
      Sildenafil is more effective in treating ED. Clinic trials are important for
      proper dose titration and appropriate education of the patients.

PMID- 16801936
TI  - The individual relationship between heart rate and oxygen uptake in people with a
      tetraplegia during exercise.
AB  - STUDY DESIGN: Descriptive study. OBJECTIVE: To examine the individual heart rate
      oxygen uptake (HR-VO(2)) relationship during exercise in persons with tetraplegia
      (TP). SETTING: Rehabilitation Centre Heliomare, Wijk aan Zee, The Netherlands.
      METHODS: The HR-VO(2) relationship was determined in untrained subjects with
      motor complete TP (C5 or C6, n=10 and C7 or C8, n=10) during a discontinuous
      graded exercise hand cycle test. The mean HR and VO(2) of the final 60 s of 2-min
      exercise blocks were used for calculation of the individual correlation
      coefficient and the standard error of the estimate (SEE). RESULTS: Two subjects
      of the C5-C6 group were not able to complete the test. Individual Pearson's
      correlation coefficients (r) ranged from 0.68 to 0.97 and SEE from 2.6 to 22.4%
      VO(2)-Reserve (VO(2)R). The mean Pearson's r and SEE were 0.81+/-0.12 and 10.6+/
      5.6% VO(2)R in the C5-C6 group and 0.91+/-0.07 and 7.0+/-3.2% VO(2)R in the C7-C8
      group, respectively. Two subjects of the C5-C6 group and six subjects of the C7
      C8 group attained a linear HR-VO(2) relationship with an acceptable SEE (< or
      =6.0%) and r (>0.90). CONCLUSIONS: The HR-VO(2) relationship appeared linear in
      only eight out of 18 subjects. An individual analysis of the HR-VO(2)
      relationship is necessary to determine whether HR can be used to quantify
      exercise intensity. The use of HR to prescribe training intensity should be
      reconsidered in persons with TP. SPONSORSHIP: This study is supported from a
      grant by ZON-MW.

PMID- 16801937
TI  - Clinical implications of genetic polymorphisms on stomach cancer drug therapy.

PMID- 16801938
TI  - Genetic diversity and function in the human cytosolic sulfotransferases.
AB  - Amino-acid substitutions, which result from common nonsynonymous (NS)
      polymorphisms, may dramatically alter the function of the encoded protein.
      Gaining insight into how these substitutions alter function is a step toward
      acquiring predictability. In this study, we incorporated gene resequencing,
      functional genomics, amino-acid characterization and crystal structure analysis
      for the cytosolic sulfotransferases (SULTs) to attempt to gain predictability
      regarding the function of variant allozymes. Previously, four SULT genes were
      resequenced in 118 DNA samples. With additional resequencing of the remaining
      eight SULT family members in the same DNA samples, a total of 217 polymorphisms
      were revealed. Of 64 polymorphisms identified within 8785 bp of coding regions
      from SULT genes examined, 25 were synonymous and 39 were NS. Overall, the
      proportion of synonymous changes was greater than expected from a random
      distribution of mutations, suggesting the presence of a selective pressure
      against amino-acid substitutions. Functional data for common variants of five
      SULT genes have been previously published. These data, together with the SULT1A1
      variant allozyme data presented in this paper, showed that the major mechanism by
      which amino acid changes altered function in a transient expression system was
      through decreases in immunoreactive protein rather than changes in enzyme
      kinetics. Additional insight with regard to mechanisms by which NS single
      nucleotide polymorphisms alter function was sought by analysis of evolutionary
      conservation, physicochemical properties of the amino-acid substitutions and
      crystal structure analysis. Neither individual amino-acid characteristics nor
      structural models were able to accurately and reliably predict the function of
      variant allozymes. These results suggest that common amino-acid substitutions may
      not dramatically alter the protein structure, but affect interactions with the
      cellular environment that are currently not well understood.

PMID- 16801939
TI  - The changing pattern of management for hormone-refractory, metastatic prostate
      cancer.
AB  - Prostate cancer responds initially to hormonal manipulation by androgen
      withdrawal and peripheral androgen blockade. The inevitable progression to a
      hormone-refractory state is accompanied by an exacerbation of local symptoms and
      metastatic spread, principally to the bones, which has a considerable impact on
      quality of life and survival. Treatment of hormone-refractory prostate cancer is
      palliative, and surgery and radiotherapy are used for the relief of lower urinary
      tract symptoms and localized painful bony metastases. Systemic treatments are not
      widely accepted in this setting, but clinical trials have demonstrated the
      potential for bone targeting agents such as strontium-89 and the bisphosphonates
      to palliate painful bone metastases and to delay progression in certain settings.
      Chemotherapy with mitozantrone in combination with steroids has previously been
      shown to have palliative benefits and to delay progression. The additional costs
      incurred by the use of chemotherapy or bone-targeting therapies may be offset by
      gains in overall care with fewer in-patient admissions compared with steroid
      monotherapy. Recent clinical trials have demonstrated that docetaxel
      significantly improves patient quality of life, and importantly, increases
      survival. Future studies investigating the timing of chemotherapy, combinations
      with existing treatments or other novel therapies are underway.

PMID- 16801940
TI  - Have we been barking up the wrong tree: can a good night's sleep make us slimmer?

PMID- 16801941
TI  - Endothelial dysfunction and arterial abnormalities in childhood obesity.
AB  - Rates of overweight and obesity in both adults and children have risen sharply
      during the past 20 years. The reasons for this escalation in obesity are not
      fully determined, however, sedentary lifestyle and dietary changes in combination
      with genetic predisposition are probably involved. Clinical cardiovascular
      disease, including myocardial infarction and stroke, are usually only manifest in
      the fifth decade of life or beyond. However, the earliest physical signs of
      atherosclerosis, the underlying disease process that leads to these events, may
      be present from early childhood. There are now a variety of noninvasive tests
      used to assess both the structural and functional properties of the vasculature
      and in vivo changes suggestive of 'early atherosclerosis' have now been
      characterised. These have allowed not only an increased understanding of the
      atherosclerotic changes to the vasculature that accompany overweight and obesity
      in children, but have also allowed serial study of the effects of diet and
      exercise interventions on early atherosclerosis changes, in childhood obesity.

PMID- 16801942
TI  - Variation in physical activity lies with the child, not his environment: evidence
      for an 'activitystat' in young children (EarlyBird 16).
AB  - OBJECTIVE: There is currently wide interest in the physical activity of children,
      but little understanding of its control. Here, we use accelerometers to test the
      hypothesis that habitual activity in young children is centrally, rather than
      environmentally, regulated. By central regulation we mean a classic biological
      feedback loop, with a set-point individual to the child, which controls his/her
      activity independently of external factors. DESIGN: Non-intervention,
      observational and population-based, set in the home and at school. RESULTS: Girls
      were systematically less active than boys, and both weekday/weekend day and year
      on-year activities were correlated (r=0.43-0.56). A fivefold variation in
      timetabled PE explained less than 1% of the total variation in physical activity.
      The activity cost of transport to school was only 2% of total activity, but over
      90% of it was recovered elsewhere in the day. The weekly activity recorded by
      children in Plymouth was the same (to within <0.3%) as that recorded
      independently in Glasgow, 800 km away. Total daily activity was unrelated to time
      reportedly spent watching TV. INTERPRETATION: The correlations within groups and
      the similarities between them suggest that physical activity in children is under
      central biological regulation. There are implications both for public health
      planners and for the potentially novel signalling pathways involved.

PMID- 16801943
TI  - The gender insulin hypothesis: why girls are born lighter than boys, and the
      implications for insulin resistance.
AB  - Girls are born lighter than boys. The consistency of this observation across
      different populations is striking, suggesting that it may have fundamental
      significance for those conditions linked with lower birth weight, such as
      diabetes. Previous hypotheses relating low birth weight to subsequent diabetes
      have addressed differences in insulin resistance within the sexes, not between
      them. Here, we propose that gender-specific genes affecting insulin sensitivity
      are responsible for the gender difference in birth weight--the genetically more
      insulin resistant female fetus is less responsive to the trophic effects of
      insulin and is therefore smaller. These genes also render female subjects more
      susceptible to diabetes, explaining why reports of type 2 diabetes (T2D) in
      younger populations show a female preponderance. Consistent with our proposal,
      concentrations of insulin and/or its propeptides are higher at birth in female
      populations and they are intrinsically more insulin resistant throughout life,
      with attendant impact on their metabolism, and the regressions describing the
      relationship between insulin resistance and adiposity in female and male subjects
      have similar gradients, but different constants. These gender-specific genes have
      a demonstrable impact on fetal growth and insulin resistance. Diabetes and
      cardiovascular disease are thought to be driven by insulin resistance, and the
      observations reported here may help to focus the search for genes that control
      it.

PMID- 16801944
TI  - Influence of extracurricular sport activities on body composition and physical
      fitness in boys: a 3-year longitudinal study.
AB  - OBJECTIVE: To analyse the effect of extracurricular physical activities on fat
      mass accumulation and physical fitness during growth in early pubertal males.
      DESIGN: Longitudinal study. SUBJECTS: A total of 42 male children (9.4+/-1.4
      years, Tanner I-II and 12.7+/-1.5 years, Tanner III-IV, before and after the 3.3
      years follow-up, respectively), randomly sampled from the population of Gran
      Canaria (Spain), 26 of them physically active (PA, at least 3 h per week during 3
      years) and 16 non-physically active (non-PA). MEASUREMENTS: Body composition
      (dual-energy X-ray absorptiometry), anthropometrics (body circumferences and
      skinfolds) and physical fitness variables (dynamic and isometric force, anaerobic
      capacity and maximal aerobic power) were determined in all subjects. RESULTS:
      Both groups had comparable body sizes at the start and the end of the study. Body
      mass index increased with growth more in the PA than in the non-PA group
      (P<0.05). However, fat mass accumulation with growth was lower in the PA than in
      the non-PA (P<0.05). There was a positive relationship between the increment of
      total and trunkal fat mass, especially in non-active children (r2=0.93). In
      contrast, there was an inverse relationship between the total lean mass growth
      and the accumulation of total and regional fat mass (r=-0.37 to -0.41, all
      P<0.05). Physical fitness was maintained in the PA, while it worsened in the non
      PA children. CONCLUSIONS: Without any dietary intervention, children who
      regularly participate in at least 3 h per week of sports activities are more
      protected against total and regional fat mass accumulation. They also increase
      their total lean and bone mass to a greater extent than children who do not
      participate in extracurricular sport activities. In addition, PA children
      maintain their physical fitness during growth, while it deteriorates in the non
      PA children.

PMID- 16801945
TI  - Obesity in Korean pre-adolescent school children: comparison of various
      anthropometric measurements based on bioelectrical impedance analysis.
AB  - OBJECTIVES: To examine the relationships between body mass index (BMI),
      percentage-weight-for-height (PWH) and percentage body fat (PBF), and to compare
      their validity based on PBF with the BMI criteria of International Obesity Task
      Force (IOTF) for childhood obesity in Korean pre-adolescent school children.
      DESIGN: Statistical comparative analysis for anthropometric measures. SUBJECTS:
      Korean pre-adolescent children (438 boys and 454 girls, aged 8-12 years, mean BMI
      19.5+/-3.4 kg/m2). MEASUREMENTS: Body mass index and PWH were calculated as body
      size indices from height and weight. Hand-to-foot bioelectrical impedance
      analysis (BIA) was performed to obtain PBF values, with obese children defined as
      PBF above 35%. Sensitivity and specificity were displayed with the gold standard
      of PBF, and receiver operating characteristic (ROC) curves were used to assess
      the performance of BMI and PWH in detecting obesity. RESULTS: The prevalence of
      obesity varied by the criteria: 18.8% by Korean BMI standards for 95 percentile,
      11% by the IOTF-BMI 30 kg/m2 and 29.4% by Korean PWH cutoffs. Body mass index and
      PWH were significantly correlated with PBF after adjusting for age, 0.910
      (P<0.01) and 0.915 (P<0.01), respectively. The sensitivity and specificity of the
      PWH cutoffs were 0.909 and 0.882, respectively. The local BMI 95 percentiles had
      lower sensitivity (0.714) and specificity (0.790). The IOTF-BMI definition showed
      much lower sensitivity (0.457) and higher specificity (0.990). The BMI cutoffs
      corresponding with the highest accuracy were smaller than IOTF-BMI 30 kg/m2 for
      all age groups in both boys and girls. CONCLUSION: The prevalence of obesity
      among Korean pre-adolescent children widely varied according to the diagnostic
      criteria applied. Universally recommended cutoffs for children by IOTF showed the
      lowest sensitivity among the criteria used, and may therefore underestimate
      obesity in this population.

PMID- 16801946
TI  - Soft drink consumption and excess weight gain in Australian school students:
      results from the Nepean study.
AB  - We studied the relation between soft drink/cordial (a sweet, flavoured,
      concentrated syrup that is mixed with water to taste), fruit juice/drink and milk
      consumption in mid-childhood, and body mass index (BMI) status in early
      adolescence in a contemporary Australian cohort. In 1996/7, 268 children (136
      males) were recruited from western Sydney at baseline (mean+/-s.d.: 7.7+/-0.6
      years), and at follow-up 5 years later (13.0+/-0.2 years). Height and weight were
      measured at both time periods and overweight and obesity defined using the
      International Obesity TaskForce criteria. Beverage consumption was calculated
      from a 3-day food record at baseline. Median carbohydrate intake from soft
      drink/cordial was 10 g higher (P=0.002) per day in children who were
      overweight/obese at follow-up compared to those who had an acceptable BMI at both
      baseline and follow-up. Intakes of soft drink/cordial in mid-childhood, but not
      fruit juice/fruit drink and milk, were associated with excess weight gain in
      early adolescence.

PMID- 16801947
TI  - Is infant growth changing?
AB  - Weight gain between birth and 9 months of 12 903 term Millennium Cohort Study
      infants was investigated in order to determine differences according to sex,
      ethnicity and country of birth. The standardised weights and weight gains were
      also compared with a cohort of mainly white infants born 10 years earlier to
      determine whether weight gain has changed over the last decade. There were
      significant differences between ethnic groups, with black infants showing the
      largest weight gain and Asians the smallest. White boys born in England and
      Scotland grew relatively faster than girls, but there were no significant gender
      differences among the other ethnic groups or among infants born in Ireland and
      Wales. There was very little difference in weight gain between white English
      Millennium cohort infants and the earlier cohort, suggesting that the current
      epidemic of childhood obesity starts after 9 months of age.

PMID- 16801949
TI  - The SNAP-25 gene is associated with cognitive ability: evidence from a family
      based study in two independent Dutch cohorts.
AB  - The synaptosomal-associated protein of 25 kDa (SNAP-25) gene plays an integral
      role in synaptic transmission, and is differentially expressed in the mammalian
      brain in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra
      and cerebellar granular cells. Recent studies have suggested a possible
      involvement of SNAP-25 in learning and memory, both of which are key components
      of human intelligence. In addition, the SNAP-25 gene lies in a linkage area
      implicated previously in human intelligence. In two independent family-based
      Dutch samples of 391 (mean age 12.4 years) and 276 (mean age 37.3 years)
      subjects, respectively, we genotyped 12 single-nucleotide polymorphisms (SNPs) in
      the SNAP-25 gene on 20p12-20p11.2. From all individuals, standardized
      intelligence measures were available. Using a family-based association test, a
      strong association was found between three SNPs in the SNAP-25 gene and
      intelligence, two of which showed association in both independent samples. The
      strongest, replicated association was found between SNP rs363050 and performance
      IQ (PIQ), where the A allele was associated with an increase of 2.84 PIQ points
      (P=0.0002). Variance in this SNP accounts for 3.4% of the phenotypic variance in
      PIQ.

PMID- 16801950
TI  - Evidence for association of DNA sequence variants in the phosphatidylinositol-4
      phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia.
AB  - Linkage studies in schizophrenia have identified a candidate region on chromosome
      10p14-11 as reported for several independent samples. We investigated association
      of DNA sequence variants in a plausible candidate gene located in this region,
      the gene for phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A), in a
      sample of 65 sib-pair families for which linkage had been reported. Evidence for
      association was obtained for 15 polymorphisms spanning 73.6 kb in the genomic
      region of the gene between intron 4 and the 3' untranslated region, a region with
      high degree of linkage disequilibrium. Single nucleotide polymorphism (SNP)
      rs10828317 located in exon 7 and causing a non-synonymous amino-acid exchange
      (asparagine/serine) produced a P-value of 0.001 (experiment-wide significance
      level 0.00275) for over-transmission of the major allele coding for serine,
      analysed by transmission disequilibrium test using FAMHAP. Association of this
      SNP with schizophrenia has been also described in a sample of 273 Dutch
      schizophrenic patients and 580 controls (P=0.0004). PIP5K2A is involved in the
      biosynthesis of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), one of the key
      metabolic crossroads in phosphoinositide signalling. PI(4,5)P2 plays a role in
      membrane transduction of neurotransmitter signals as well as in intracellular
      signalling, pathways that may be impaired in schizophrenia.

PMID- 16801951
TI  - Cellular and molecular mechanisms of hippocampal activation by acute stress are
      age-dependent.
AB  - The effects of stress, including their putative contribution to pathological
      psychiatric conditions, are crucially governed by the age at which the stress
      takes place. However, the cellular and molecular foundations for the impact of
      stress on neuronal function, and their change with age, are unknown. For example,
      it is not known whether 'psychological' stress signals are perceived by similar
      neuronal populations at different ages, and whether they activate similar or age
      specific signaling pathways that might then mediate the spectrum of stress-evoked
      neuronal changes. We employed restraint and restraint/noise stress to address
      these issues in juvenile (postnatal day 18, [P18]) and adult rats, and used
      phosphorylation of the transcription factor CREB (pCREB) and induction of c-fos
      as markers of hippocampal neuronal responses. Stress-activated neuronal
      populations were identified both anatomically and biochemically, and selective
      blockers of the stress-activated hippocampal peptide, corticotropin-releasing
      hormone (CRH) were used to probe the role of this molecule in stress-induced
      hippocampal cell activation. Stress evoked strikingly different neuronal response
      patterns in immature vs adult hippocampus. Expression of pCREB appeared within
      minutes in hippocampal CA3 pyramidal cells of P18 rats, followed by delayed
      induction of Fos protein in the same cell population. In contrast, basal pCREB
      levels were high in adult hippocampus and were not altered at 10-120 min by
      stress. Whereas Fos induction was elicited by stress in the adult, it was
      essentially confined to area CA1, with little induction in CA3. At both age
      groups, central pretreatment with either a nonselective blocker of CRH receptors
      (alpha-helical CRH [9-41]) or the CRF1-selective antagonist, NBI 30775, abolished
      stress-evoked neuronal activation. In conclusion, hippocampal neuronal responses
      to psychological stress are generally more rapid and robust in juvenile rats,
      compared to fully mature adults, and at both ages, CRH plays a key role in this
      process. Enhanced hippocampal response to stress during development, and
      particularly the activation of the transcription factor CREB, may contribute to
      the enduring effects of stress during this period on hippocampal function.

PMID- 16801952
TI  - Subtyping schizophrenia: implications for genetic research.
AB  - Phenotypic variability and likely extensive genetic heterogeneity have been
      confounding the search for the causes of schizophrenia since the inception of the
      diagnostic category. The inconsistent results of genetic linkage and association
      studies using the diagnostic category as the sole schizophrenia phenotype suggest
      that the current broad concept of schizophrenia does not demarcate a homogeneous
      disease entity. Approaches involving subtyping and stratification by covariates
      to reduce heterogeneity have been successful in the genetic study of other
      complex disorders, but rarely applied in schizophrenia research. This article
      reviews past and present attempts at delineating schizophrenia subtypes based on
      clinical features, statistically derived measures, putative genetic indicators,
      and intermediate phenotypes, highlighting the potential utility of multidomain
      neurocognitive endophenotypes.

PMID- 16801953
TI  - MAOA, maltreatment, and gene-environment interaction predicting children's mental
      health: new evidence and a meta-analysis.
AB  - Previous research on adults has shown that a functional polymorphism in the
      promoter region of the monoamine oxidase A (MAOA) gene moderates the impact of
      childhood maltreatment on risk for developing antisocial behavior. Thus far,
      attempts to replicate this finding have been mixed. The current study (i)
      presents new data investigating this finding in a sample of 975 seven-year-old
      boys, and (ii) evaluates the extant data by conducting a meta-analysis of
      published findings. We replicated the original finding by showing that the MAOA
      polymorphism moderates the development of psychopathology after exposure to
      physical abuse, we extended the finding to childhood closer in time to the
      maltreatment experience, and we ruled-out the possibility of a spurious finding
      by accounting for passive and evocative gene-environment correlation. Moreover,
      meta-analysis demonstrated that across studies, the association between
      maltreatment and mental health problems is significantly stronger in the group of
      males with the genotype conferring low vs high MAOA activity. These findings
      provide the strongest evidence to date suggesting that the MAOA gene influences
      vulnerability to environmental stress, and that this biological process can be
      initiated early in life.

PMID- 16801954
TI  - Tissue differential expression of lycopene beta-cyclase gene in papaya.
AB  - Carotene pigments in flowers and fruits are distinct features related to fitness
      advantages such as attracting insects for pollination and birds for seed
      dispersal. In papaya, the flesh color of the fruit is considered a quality trait
      that correlates with nutritional value and is linked to shelf-life of the fruit.
      To elucidate the carotenoid biosynthesis pathway in papaya, we took a candidate
      gene approach to clone the lycopene beta-cyclase gene, LCY-B. A papaya LCY-B
      ortholog, cpLCY-B, was successfully identified from both cDNA and bacterial
      artificial chromosome (BAC) libraries and complete genomic sequence was obtained
      from the positive BAC including the promoter region. This cpLCY-B shared 80%
      amino acid identity with citrus LCY-B. However, full genomic sequences from both
      yellow- and red-fleshed papaya were identical. Quantitative real-time PCR (qPCR)
      revealed similar levels of expression at six different maturing stages of fruits
      for both yellow- and red-fleshed genotypes. Further expression analyses of cpLCY
      B showed that its expression levels were seven- and three-fold higher in leaves
      and, respectively, flowers than in fruits, suggesting that cpLCY-B is down
      regulated during the fruit ripening process.

PMID- 16801955
TI  - What is the optimal gestational age for delivery?

PMID- 16801956
TI  - The impact of the interaction between increasing gestational age and obstetrical
      risk on birth outcomes: evidence of a varying optimal time of delivery.
AB  - OBJECTIVE: To estimate the gestational age ranges that result in optimal birth
      outcomes for each of four risk-defined groups. STUDY DESIGN: Retrospective cohort
      study of singleton late third-trimester deliveries at a large urban teaching
      hospital between July 1995 and September 2003. Low-risk, advanced maternal age,
      hypertensive and diabetic patients were identified and grouped. Rates, by day of
      gestation at delivery, of cesarean delivery, major maternal perineal trauma, low
      5-min APGAR score and NICU admission were determined for each study group.
      RESULTS: Each study group had meaningful changes in rates of obstetric outcomes
      as a function of gestational age at delivery and these patterns differed from
      group to group. A unique optimal time of delivery (OTD) was estimated for each
      group. The low-risk group OTD was calculated to be 37 weeks 1 day to 41 weeks 0
      day; the advanced maternal age group OTD was 38 weeks 5 days to 39 weeks 6 days;
      the hypertension group OTD was 39 weeks 2 days to 40 weeks 1 day; and the
      diabetes mellitus group OTD was 40 weeks 3 days to 41 weeks 1 day. CONCLUSIONS:
      The OTD varied based on obstetrical risk. Strategies to increase the proportion
      of deliveries that occur within the OTD for specific risk-defined groups could
      theoretically improve birth outcomes.

PMID- 16801957
TI  - Seeing baby: women's experience of prenatal ultrasound examination and unexpected
      fetal diagnosis.
AB  - OBJECTIVE: Although prenatal ultrasound (US) is a common clinical undertaking
      today, little information is available about women's experience of the procedure
      from the perspective of women themselves. The objective of this study was to
      explore women's experience of undergoing a routine prenatal US examination
      associated with an unexpected fetal diagnosis. STUDY DESIGN: Qualitative methods
      were used to explore the prenatal US experience of 13 women. Five women were
      given unexpected news of multiple pregnancy and eight women were given unexpected
      news of congenital fetal abnormality. One in-depth audio-taped interview was
      conducted with each woman. Content analysis of interview data identified themes
      common to women's experience of US. RESULTS: Identified themes of women's
      experience of routine prenatal US examination associated with an unexpected fetal
      diagnosis are: experiencing the setting, sensing information, feeling
      connected/disconnected, the power of the image, and communication rules.
      CONCLUSIONS: Women's experience of prenatal US examination is influenced by
      physical and environmental factors and by the behaviors of the US examiner.
      Behaviors of the examiner contribute to a woman's labeling of the US experience
      as positive or negative. Women identify being objectified by the examination and
      experience poor communication patterns after a fetal US diagnosis. Women's
      description of the US screen image as a baby suggests it is a powerful influence
      on subsequent clinical and ethical decision-making about the pregnancy.

PMID- 16801958
TI  - Early and aggressive nutritional strategy (parenteral and enteral) decreases
      postnatal growth failure in very low birth weight infants.
AB  - OBJECTIVE: To compare postnatal growth and nutritional deficits after the
      implementation of two different nutritional strategies in two consecutives
      periods of time. METHODS: An early and aggressive nutritional regimen was used in
      a cohort of 117 very low birth weight (VLBW) infants. Amino acids were
      administered at the rate of 1.5 g/kg/day along with 5.6 mg/k/min of glucose flow
      on day 1 of life, and progressively increased to 4 g/kg/day and 13 mg/kg/min.
      Intravenous lipids were started at 0.5 g/kg/day at 24 h from birth, and increased
      to 3.5 g/kg/day; enteral feeding was begun at day 1 of life. Uni- and
      multivariate analyses were used to compare this group with the conventional group
      of 65 VLBW infants conservatively fed. RESULTS: Univariate analysis showed that
      in the aggressive group there was a 66% reduction in the risk of post natal
      malnutrition at 40 weeks of postmenstrual age (OR 0.34; 95% CI 0.17-0.67). This
      difference persisted in the multivariate analysis. Energy and protein deficits
      were lower in the aggressive group (P < 0.001). CONCLUSIONS: Early and aggressive
      introduction of total parenteral nutrition and enteral feeding resulted in better
      growth in weight, length and head circumference, and a reduction of nutritional
      deficits at 40 weeks of postmenstrual age.

PMID- 16801959
TI  - Dietary nucleotides and preterm infant nutrition.

PMID- 16801960
TI  - Caudal regression sequence: vascular origin?
AB  - Caudal regression sequence (CRS) is a rare congenital defect of the lower spinal
      segments and the neural tube. Motor symptoms as well as neurological deficits and
      loss of bladder and bowel function are usually present. CRS is also associated
      with anomalies in other systems such as the gastrointestinal and genitourinary
      tract. Etiology and pathogenesis are poorly understood.A newborn presented with
      anomalies of the spinal column (lumbosacral) with absence/hypoplasia of the 12th
      thoracic and first lumbar vertebral anomaly body. Bladder and bowel initially
      were functional. MR-angiography exhibited an anomaly of the unpaired vessels
      originating from the aorta, a likely relict of a persisting vitelline artery.
      These findings indicate a potential vascular genesis of CRS, much as in
      sirenomelia.

PMID- 16801962
TI  - Early postnatal nutritional requirements of the very preterm infant based on a
      presentation at the NICHD-AAP workshop on research in neonatology.
AB  - Normal fetal nutrition is a useful guide for understanding postnatal nutrition of
      infants born very preterm. Fetal lipid uptake gradually increases towards term
      and is primarily used to produce fat in adipose tissue, with essential fatty acid
      uptake providing necessary structural and functional elements in membranes of
      cells in the central nervous system. Fetal glucose uptake and utilization rates
      are nearly twice as high at 23-26 weeks gestation as they are at term,
      contributing primarily to energy production and glycogen formation. Amino-acid
      uptake by the fetus is two-to threefold greater at 23-26 weeks gestation than at
      term and is required to meet the very high fractional protein synthesis and
      growth rates at this gestational period; amino acids also contribute
      significantly to fetal energy production. In contrast, after birth most of the
      very preterm infants are fed more lipid and glucose and less amino acids and
      protein than they need. Not surprisingly, therefore, very preterm infants
      accumulate fat but remain relatively growth restricted at term gestational age
      compared to those infants who grew normally in utero, and this postnatal growth
      restriction has long-term adverse growth, development, and health consequences.
      More thorough understanding of the unique nutritional, metabolic, and growth
      requirements of the normally growing fetus and the very preterm infant, once
      born, are needed to determine optimal nutritional strategies to improve the
      outcome of preterm infants.

PMID- 16801963
TI  - NICHD: AAP workshop on neonatology research and training areas of research in
      neonatal gastroenterology.
AB  - Future research in neonatal and developmental gastroenterology should include
      inquiry well beyond finding a cure or better preventative measures against
      necrotizing enterocolitis. The gastrointestinal (GI) tract acts not only as a
      digestive-absorptive organ; it also serves major endocrine and neural functions.
      It encompasses a vast surface area exposed to the external environment and plays
      a major role in both innate and adaptive immunity. Numerous short- and long-term
      health benefits could be derived from a better understanding of the developing GI
      tract.

PMID- 16801964
TI  - Basic and translational neonatal neuroscience research: whither goest the future
      of physician-scientists?
AB  - OBJECTIVES: In light of declining numbers of physician-scientists, the goal of
      this project was to identify strategies to invigorate and attract new talent to
      clinical research in the field of pediatric neurosciences. DESIGN: To develop a
      broad perspective, a program of direct questions was addressed to both US and non
      US physicians at all stages of career development. RESULTS: Respondents
      identified numerous promising avenues of research but also indicated obstacles to
      research progress at all stages of career development including medical students,
      resident physicians, junior medical faculty, mid-career faculty, and senior
      faculty. At each career stage, ideas were offered to attract resources for, build
      prestige for, and motivate commitment for participation in clinical research.
      CONCLUSIONS: Creative promotion of clinical research at all stages of medical
      education and career development offers great promise to expand current physician
      scientist numbers, and thereby stimulate many exciting advances in medicine.

PMID- 16801965
TI  - National Institute of Child Health and Human Development (NICHD) and American
      Academy of Pediatrics (AAP) workshop on research in neonatal and perinatal
      medicine.

PMID- 16801966
TI  - Neonatology fellowship training in research pertaining to development and follow
      up.
AB  - The methodology of the study of the short- and long-term outcomes has changed
      over the 30-40 years since the indroduction of neonatal intensive care. The
      training of neonatal fellows in research pertaining to development and follow-up
      currently needs to include study of epidemiology and biostatistics, knowledge
      concerning normal and abnormal growth and development throughout the life span
      and clinical skills and/or knowledge concerning the assessment of neurologic and
      developmental outcomes.

PMID- 16801967
TI  - Operational research on perinatal epidemiology, care and outcomes.
AB  - Traditionally, neonatal-perinatal medicine has been concerned with two areas of
      research: basic and translational. A third area, perinatal epidemiology/health
      outcomes research addresses those factors that impede and promote the clinical
      actualization of the advances developed by basic and translational research.
      Unfortunately, research and training in perinatal epidemiology and outcomes
      analysis have not kept pace with our need to understand the interplay between
      risk, intervention, structure and outcome. This knowledge is essential to the
      development of the clinical/organizational and training strategies that will
      enable perinatal medicine to fully realize the promise of basic and translational
      research.

PMID- 16801968
TI  - Survey of neonatology training programs: 2002 to 2003.
AB  - The Committee on Research in Neonatology from the Section on Perinatal
      Pediatrics, American Academy of Pediatrics presents an overview of the update of
      the Neonatal-Perinatal Training Program Survey obtained in 2002 to 2003. Our goal
      was to update the last survey in 1996 and to begin to assess research resources
      and the potential for training life-career physician scientists (basic and
      clinical investigators).

PMID- 16801969
TI  - Training and retaining of underrepresented minority physician scientists - an
      African-American perspective: NICHD AAP workshop on research in neonatal and
      perinatal medicine.

PMID- 16801970
TI  - Training and retaining of underrepresented minority physician scientists - a
      Hispanic perspective: NICHD-AAP workshop on research in neonatology.
AB  - In a workshop organized by NICHD and the AAP in January 2004, we addressed and
      discussed issues related to a Hispanic perspective in Training and Retaining of
      underrepresented minority physician scientists in the United States. A review of
      the literature related to training of underrepresented minority physicians in the
      United States (US) was performed, giving emphasis to those related to the
      Hispanic population. Success and failure in training and retention of Hispanic
      physician scientists and trainees was examined. An underrepresentation of
      Hispanic minorities in medical research workforce was found. This fact has
      recently resulted in efforts to increase their recruitment and there is a mandate
      by the National Institute of Health (NIH) for their inclusion. The Hispanic
      population in the US has increased rapidly, with diversity among the Hispanics in
      their personal and professional behavior. Significant disparities in health,
      health risk factors and access to health care manifested by an increased burden
      of illness and death have been documented. There in an undersupply of academic
      Hispanic neonatologist. Factors such as availability of academic employment,
      limited research funding in pediatrics, managed care and large debt burden of the
      US medical graduates interfere with recruitment of Hispanic trainees and academic
      physician scientist. Possible solutions, including recognition research awards,
      revision of NIH policies in awarding funds for neonatology, establishing
      strategies to improve minorities' acceptance, participation in research and
      increase accrual of Hispanic population in clinical trials should be given
      priority.

PMID- 16801971
TI  - The cardiopulmonary system: research and training opportunities.
AB  - The new biology has the potential to provide mechanistic insights into the causes
      and progression of complex cardiopulmonary diseases such as congenital heart
      disease and bronchopulmonary dysplasia. Such research requires collaborative
      investigation supported by sophisticated infrastructures and core facilities.
      Translating basic observations to clinical outcomes will require networks for
      collaborative translational research. The research initiatives require
      excellently trained and motivated clinician-scientists, but there are numerous
      barriers to the training and support of clinician-scientists in cardiology and
      neonatology.

PMID- 16801972
TI  - Perspectives of recent trainees on career choices in neonatology.
AB  - A major goal for neonatology training programs is to produce neonatologists who
      will pursue careers that combine clinical and research responsibilities. However,
      there appears to be a continuing decline in the number of trainees who choose
      academic, as opposed to private sector, jobs. The reason for this decline is
      perhaps best addressed by the people making career choices now, the recent
      trainees. Although many factors influence any individual's career choice,
      information from recent fellows indicates that several major factors play a
      strong role: finances; time demands; adequacy of research training; and academic
      institutions' attitudes toward recent trainees. Whereas the first two factors
      have been addressed by prior studies, the latter two factors have been less
      explored. The responses of a few recent trainees to an informal survey will be
      used to guide a discussion that focuses on the factors of research training and
      academic status. Ways to improve the success of training programs in producing
      academic neonatologists will be suggested, including the proposal of a research
      training curriculum, changes in the structure of post-fellowship academic status
      and increased encouragement of collaborative research efforts. A future survey of
      a broad group of recent trainees about their career choices and about proposals
      for training changes, such as those considered here, is needed to evaluate
      programs aimed at increasing the number of neonatologists engaged in research.
      Journal of Perinatology (2006) 26, S53-S56. doi:10.1038/sj.jp.7211527.

PMID- 16801973
TI  - Basic and translational research in neonatal pharmacology.
AB  - Pharmacologic study is needed in the extremely immature newborns who currently
      survive. Study is needed of both the drug treatment previously established in
      more mature neonates and of novel drug therapy. Carefully controlled studies are
      needed to identify accurately both beneficial and harmful drug therapy and the
      mechanisms of that toxicity. Careful pharmacologic study of drug disposition and
      its mechanisms might lead to dosing paradigms or patient selection that minimize
      toxicity and maximize efficacy. In vivo, translational models of neonatal
      diseases are limited, but can be used to identify novel treatments and study
      mechanisms of established, successful therapy. Findings from such studies can
      generate hypotheses for study in humans leading to a continuing scientific
      interchange from bedside to bench to bedside. Similarly, clinical observations
      can generate hypotheses for study in translational models where more invasive
      analyses are possible. Specific areas of drug treatment should focus on neonatal
      disorders with long-term, adverse outcomes, such as chronic lung disease, that is
      amenable to translational study with animal models. National data show a
      progressive decrease in the clinician-scientist pool entering biomedical
      research. The future of neonatal pharmacology studies requires an increase in
      training programs for the physician-scientist whose clinical education in
      neonatology can be complemented by rigorous basic-science training. Success as a
      clinician-scientist will require collaboration with full-time basic scientists
      who can continue studies during periods of clinical work and provide critical
      study methodology to the overall study design. Such a work environment must be
      supported by academic institutions and may require more flexibility in the
      promotion and tenure schedule and process, such as the nature of what it rewards.
      To complement this, the NIH could modify its grant reporting process to identify
      co-investigators in studies who may provide unique input to the study concepts
      and design, such as clinical correlations or clinical investigations.

PMID- 16801975
TI  - First in vivo evidence of microRNA-induced fragile X mental retardation syndrome.

PMID- 16801976
TI  - Response to paper by Molloy et al.: linkage on 21q and 7q in autism subset with
      regression.

PMID- 16801977
TI  - The procholinergic effects of the atypical antipsychotic olanzapine are
      independent of muscarinic autoreceptor inhibition.

PMID- 16801980
TI  - A New Alkylation-Elimination Method for Synthesis of Antiviral
      Fluoromethylenecyclopropane Analogues of Nucleosides.
AB  - A new method for the synthesis of fluoromethylenecyclopropane nucleosides by
      alkylation-elimination procedure is described. Fluorination of
      methylenecyclopropane carboxylate 6 gave fluoroester 7. Treatment of 7 with
      phenylselenenyl bromide afforded the desired ethyl (E)-2-bromomethyl-1-fluoro-2
      phenylselenenylcyclopropane-1-carboxylate 11 in 85% yield. DIBALH reduction of 11
      gave 13, which after acetylation to 14 was reacted with 2-amino-6-chloropurine to
      give the 9-alkylated product 15 in 87% yield. Se-oxydation of 15 with hydrogen
      peroxide afforded 16, which underwent smooth elimination in a mixture of THF-DMF
      at 60 degrees C giving rise to a Z,E mixture of protected nucleosides 17.
      Deacetylation gave Z-1a and E-1a which were separated on a silica gel column.
      Both Z-1a and E-1a were converted into the respective guanine analogues Z-1b and
      E-1b.

PMID- 16801981
TI  - Potential use of freeze-drying technique for estimation of tissue water content.
AB  - Desiccation and freeze-drying methods were used for the estimation of water
      content of various rat tissues. In the desiccation method, the tissue samples
      were cut into small pieces and subsequently dried at 40 degrees C to constant
      weight. In the freeze-drying method, the prefrozen tissue samples were freeze
      dried (-50 degrees C) for 24 h. Tissue water contents obtained by the desiccation
      and freeze-drying methods were very similar, with no significant difference
      between them. Regardless of the method, the highest tissue water content was
      found in testes (0.841 +/- 0.010 ml/g for freeze-drying and 0.865 +/- 0.002 ml/g
      for desiccation); the lowest values were obtained in bone (0.254 +/- 0.007 ml/g
      for freeze-drying and 0.267 +/- 0.003 ml/g for desiccation). Upon correction for
      the water content of residual tissue blood, regardless of the drying method,
      significant differences were found between corrected and uncorrected tissue water
      values of all tissues. However, for a given method, the difference between the
      tissue water contents was not significant after correcting for residual blood.
      The water content values for all tissues (except bone) agree well with those
      published previously and obtained by desiccation. All these clearly suggest that
      the freeze-drying method can be used as an alternative to desiccation for
      estimation of tissue water content.

PMID- 16801984
TI  - Variant alleles and genotypes of alcohol dehydrogenase 3 in a Turkish population.
AB  - Alcohol dehydrogenase (ADH) is a genetically polymorphic dimeric enzyme that is
      responsible for the metabolism of alcohol. ADH3 gene encodes for the gamma
      subunit of dimeric ADH and has an important role in the function of the enzyme.
      The aim of this study was to determine the frequencies of ADH3 alleles and
      genotypes in a healthy Turkish population sample. Genotypic assay was carried out
      in 102 unrelated volunteers. DNA samples were genotyped for the ADH3*2 allele.
      The ADH3*1 and ADH3*2 allele frequencies were determined as 0.66 (95% confidence
      interval [CI] = 0.57-0.75) and 0.34 (95% CI = 0.25-0.43), respectively. The
      genotype frequencies of ADH3*1/*1, *1/*2, and *2/*2 were 39% (95% CI = 30-49),
      54% (95% CI = 44-64), and 7% (95% CI = 2-12), respectively. According to our
      results, the frequencies of variant ADH3 alleles and genotypes are similar to
      that in the other Caucasian populations.

PMID- 16801983
TI  - Effects of oral administration of some herbal extracts on food consumption and
      blood glucose levels in normal and streptozotocin-treated diabetic rats.
AB  - Previous studies in our laboratories suggest that oral administration of some
      herbal extracts reduce blood glucose concentrations in rats, possibly by
      interfering with food consumption and/or gastrointestinal absorption of food.
      Accordingly, we monitored the amounts of food consumed and body weights in
      separate groups of nondiabetic and streptozotocin-treated diabetic rats, orally
      treated with some plant extracts (20 mg 100 g -1 body weight) daily for 5 weeks.
      Control animals were administered the vehicle, citrate buffer (0.1 ml 100 g -1
      body weight). Separate groups of rats administered allopathic hypoglycemic drugs
      metformin (50 mg 100 g -1 body weight) or glibenclamide (5 microg 100 g -1 body
      weight) acted as positive control animals. After 5 weeks, blood glucose
      concentrations were reduced in all the groups. Tapinanthus nyasicus leaf, Ficus
      thoningii bark, Solanum incanum fruit, and Morus alba leaf extracts decreased
      weekly food consumption throughout the 5-week study period. Similar results were
      obtained for the groups treated with metformin or glibenclamide. However, food
      consumption was increased by S. incanum root, Aloe chabaudii leaf, or Allium
      sativum bulb extracts, and this was associated with high prevalence of diarrhea.
      The herbal extracts and metformin did not affect serum insulin concentration in
      nondiabetic rats, while glibenclamide increased serum insulin concentration. In
      conclusion, it may be inferred that the herbal extracts examined produced
      hypoglycemia, probably by interfering with either food intake or gastrointestinal
      glucose absorption (as reported for metformin). These findings merit long-term
      investigation.

PMID- 16801982
TI  - Effect of captopril in the presence of kinin B2 receptor antagonist on duration
      of survival after prolonged coronary artery ligation in hypertensive rats.
AB  - In the present investigation, we evaluated the potential effects of captopril, an
      angiotensin-converting enzyme inhibitor, in the absence and presence of kinin
      B(2) receptor antagonist (D-Arg-[Hyp3-D-Phe7]-BK) on the duration of survival
      after prolonged coronary artery ligation in spontaneously hypertensive rats
      (SHR). The captopril treatment (16 and 32 microg/kg; i.v.) resulted in a
      significant (p < 0.05) increase in survival time of SHR when compared with that
      of saline-treated control SHR. Kinin B(2) receptor antagonist (4 microg/kg; i.v.)
      pretreatment abolished (p > 0.05) the beneficial effect of captopril on the
      survival time when compared with that in saline-treated control SHR. Both the
      ligation of coronary artery and captopril treatment resulted in a significant (p
      < 0.001) fall in systolic blood pressure (SBP), diastolic blood pressure (DBP),
      and heart rate (HR) of SHR when compared with those of the saline-treated control
      SHR. In addition, captopril administration caused a significant (p < 0.05) fall
      in SBP, DBP, and HR of SHR before ligation of the coronary artery (preligation).
      However, there was no significant change (p > 0.05) in SBP, DBP, and HR between
      saline- and kinin B(2) receptor antagonist plus captopril-treated SHR during
      preligation. These finding might indicate that captopril possesses a
      cardioprotective property as demonstrated by an increase in the survival time of
      SHR. This beneficial effect of captopril is mediated via the kinin B(2) receptor
      pathway because kinin B(2) receptor antagonist pretreatment blocked the captopril
      induced increase in the survival time of SHR.

PMID- 16801985
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: Adalimumab, adenosine triphosphate,
      alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007,
      aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole,
      atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone
      dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet
      hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride,
      Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase,
      desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride,
      dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab,
      eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium,
      escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux
      sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin;
      Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin
      subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin,
      ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate,
      lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa,
      levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin,
      melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral
      insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium,
      PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole,
      prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab,
      ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus-eluting stent,
      sitaxsentan sodium, solifenacin succinate, Staphylococcus aureus vaccine;
      Tadalafil, talactoferrin alfa, talaporfin sodium, Taxus, tecadenoson, tegaserod
      maleate, telithromycin, temsirolimus, tenofovir disoproxil fumarate,
      teriparatide, terutroban sodium, tesaglitazar, tesmilifene hydrochloride, TG
      100115, tigecycline, torcetrapib; Ularitide; Valproic acid, sodium, voriconazole;
      Zotarolimus, zotarolimus-eluting stent.

PMID- 16801986
TI  - Clinical pharmacokinetics of dexketoprofen trometamol: recent studies.

PMID- 16801987
TI  - Clinical pharmacokinetics of parenteral dexketoprofen trometamol in healthy
      subjects.
AB  - Dexketoprofen trometamol, a highly water-soluble salt of the active enantiomer of
      rac-ketoprofen, is a nonsteroidal antiinflammatory drug used for pain relief. Two
      studies were conducted to determine the pharmacokinetics of the drug in healthy
      subjects following single intravenous (i.v.) and intramuscular (i.m.) doses of
      dexketoprofen. In the first study, 6 male and 6 female volunteers received 50 mg
      dexketoprofen (74 mg dexketoprofen trometamol) by i.v. bolus. In the second one,
      another 6 male and 6 female subjects received 25 mg and 50 mg of dexketoprofen by
      the i.m. route. Dexketoprofen plasma concentrations were determined by reverse
      phase high-performance liquid chromatography (HPLC). No serious adverse events
      were observed and all volunteers completed the study. The main pharmacokinetic
      parameters were determined by a noncompartmental approach. Following the i.v.
      bolus, mean (+/- SEM) area under the curve AUC0-x and clearance (CL) were 9005 +/
      422 ng.h/ml and 0.089 +/- 0.004 l/h/kg. Volumes of distribution Vi and Vss
      averaged 0.060 +/- 0.006 l/kg and 0.104 +/- 0.003 l/kg. Mean elimination half
      life (t1/2e) and MRT were 1.05 +/- 0.04 h and 1.18 +/- 0.05 h. Following single
      i.m. 25 mg and 50 mg dexketoprofen, a rapid absorption was observed, with tmax
      values ranging from 0.17 h to 0.75 h. The corresponding Cmax averaged 1851 +/-
      182 ng/ml and 3813 +/- 169 ng/ml, and mean AUC0-x were 3033 +/- 193 ng.h/ml and
      5878 +/- 228 ng.h/ml, respectively. No significant differences by gender were
      obtained following both parenteral routes. A dose proportionality in Cmax and
      AUC0-x was observed. Dexketoprofen pharmacokinetics following i.v. and i.m.
      routes, together with the availability of a single 2 ml formulation, allows for a
      potential advantageous rapid switch to the oral formulation when clinically
      possible.

PMID- 16801988
TI  - Single and repeated dose pharmacokinetics of dexketoprofen trometamol in young
      and elderly subjects.
AB  - Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of
      rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) widely used for
      pain relief. This study was conducted to determine the pharmacokinetics of this
      analgesic agent in elderly subjects and to compare them with young volunteers
      following single and repeated oral doses. Twelve healthy young and 12 elderly
      subjects received 25 mg oral dexketo- profen (equivalent to 37 mg of its
      tromethamine salt) as a single dose (day 1) and 3-day repeated doses (1 dose
      every 8 h for a total of 10 doses). Serial concentrations of dexketoprofen were
      determined in plasma and urine by a reverse-phase HPLC/ultraviolet procedure over
      24 h on day 1 and after the last 10th repeated t.i.d. dose. Compared to young
      subjects, elderly subjects showed significant increases in AUC and t1/2,z and
      decreases in CL/F following single and repeated doses. After single dosing, the
      corresponding mean +/- SD values were 5106.6 +/- 1873.0 vs. 3605.4 +/- 897.9
      ng.h/ml (p = 0.015); 1.59 +/- 0.40 vs. 1.12 +/- 0.20 h (p < 0.001); and 1.11 +/-
      0.29 vs. 1.63 +/- 0.36 ml/min/kg (p < 0.001). After the repeated dose, AUC,
      t1/2,z and CL/F averaged 5067.8 +/- 1373.4 vs. 3194.4 +/- 694.3 ng.h/ml (p <
      0.001); 1.65 +/- 0.44 vs. 1.11 +/- 0.29 h (p < 0.005); and 1.12 +/- 0.23 vs. 1.87
      +/- 0.42 ml/min/kg (p < 0.001). Median tmax was 0.5 h. Cumulative excretions in
      urine up to 24 h of unbound, conjugated and total dexketoprofen were similar
      among the groups. These results suggest that dexketoprofen elimination is reduced
      in the elderly. Although no drug accumulation in plasma was observed after single
      and repeated dosing, the renal function decline in elderly patients calls for a
      cautious dose-adjustment in this population.

PMID- 16801989
TI  - Pharmacokinetics of dexketoprofen trometamol in subjects with mild and moderate
      chronic renal insufficiency.
AB  - The influence of mild to moderate chronic renal insufficiency on the
      pharmacokinetics of dexketoprofen trometamol was evaluated. Dexketoprofen was
      administered to volunteers with mild (n = 8) or moderate (n = 8) renal impairment
      and to healthy subjects (n = 8), as a single 12.5 mg oral dose (equivalent to
      18.5 mg of the tromethamine salt). All subjects completed the study and no
      serious adverse events were recorded. Mild and moderate renal insufficiency
      increased Cmax by approximately 22% and 37%, respectively, as related to normal
      subjects (p < 0.05 for moderate renal dysfunction). No statistically significant
      differences between groups were obtained for tmax, AUC, CL/F, renal CL and V/F.
      The cumulative urinary excretion of unchanged dexketoprofen, assessed up to 24
      hours postdose, was similar in all groups (median values of 7.0%, 8.1% and 9.7%
      of the administered dose). On the contrary, cumulative urinary excretions of
      conjugated dexketoprofen decreased in subjects with mild or moderate renal
      insufficiency when compared to healthy controls (median and 95% CI for
      differences: -3.3% (-14.8% to 2.6%) and -7.3% (-22.2% to -0.2%), respectively).
      Conservatively, a dose adjustment of dexketoprofen in patients with impaired
      renal function is recommended.

PMID- 16801990
TI  - Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients
      with impaired liver function.
AB  - Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of
      rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain
      relief. This study compared the pharmacokinetics of dexketoprofen in patients
      with impaired liver function and normal subjects following single and repeated
      oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n
      = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label
      and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its
      tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8
      hours for a total of 10 doses). Dexketoprofen concentrations were determined in
      plasma and urine by reverse-phase high performance liquid chromatography (HPLC).
      Model-independent pharmacokinetic parameters were obtained. All subjects
      completed the study. No serious adverse events were recorded. Following the
      single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects),
      2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B).
      Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33
      1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and
      3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9
      ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/
      0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration,
      similar results were obtained showing no drug accumulation. As related to the
      administered dose, median excretions of unchanged and conjugated dexketoprofen in
      urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A
      subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced
      urinary excretion of conjugated dexketoprofen in hepatic patients, more evident
      in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared
      with healthy volunteers (median and 95% CI for differences: -5.4% [-19.9% to
      2.0%] and -19.4% [-45.6% to 0.4%]). Conservatively, a dose adjustment of
      dexketoprofen trometamol in patients with impaired hepatic function is
      recommended.

PMID- 16801991
TI  - Extended-release carbamazepine for acute bipolar mania: a review.
AB  - In December 2004, an extended-release capsule formulation of carbamazepine was
      approved by the U.S. Food and Drug Administration for the treatment of acute
      manic or mixed episodes associated with bipolar I disorder. This formulation
      allows twice-daily dosing and minimizes plasma carbamazepine fluctuations. The
      efficacy, safety and tolerability of the product were demonstrated with two
      pivotal randomized, placebo-controlled, double-blind monotherapy trials. These
      studies showed efficacy in bipolar I mania in patients with acute manic or mixed
      episodes. Pooled post hoc analyses documented a significant onset of effect
      within seven days, an incremental response of about 25% over placebo and a
      moderate effect size of 0.61 with no treatment-emergent depression.
      Carbamazepine's mode of action in mania is unknown, but a variety of effects on
      receptors, neurotransmitters, ion channels and binding sites have been
      documented. It has a complex pharmacokinetic profile due to autoinduction and a
      long-acting active metabolite. Carbamazepine's most frequent adverse events
      comprise dizziness, somnolence, nausea and vomiting, although these tend to
      diminish over time. It is effectively weight neutral and can provide an
      acceptable and efficacious treatment option for bipolar I mania.

PMID- 16801992
TI  - Tramiprosate.
AB  - Current treatment options for patients with Alzheimer's disease are limited to
      providing symptomatic relief, with no effects on the underlying pathophysiology.
      However, a greater understanding of the importance of beta-amyloid peptides
      (Abeta) in the pathogenesis of this disease has led to the investigation of a
      number of potential antiamyloid therapies, of which tramiprosate (Neurochem Inc.)
      is in the most advanced stage of development. Tramiprosate is a glycosaminoglycan
      (GAG) mimetic designed to interfere with the actions of Abeta early in the
      cascade of amyloidogenic events. Preclinical data have shown that tramiprosate
      reduces brain and plasma levels of Abeta, prevents fibril formation and exerts
      cytoprotective effects in the brain. The pharmacological effects have also been
      demonstrated in clinical trials of patients with mild to moderate Alzheimer's
      disease. Promising findings for the efficacy of tramiprosate, indicated by
      improvement or stabilization of cognitive function, have been shown in phase II
      clinical trials and open-label extensions of these studies. Furthermore,
      tramiprosate appears to be well tolerated with no reports of safety concerns.
      This article reviews the unique mode of action of tramiprosate and summarizes the
      available clinical information on the effects of tramiprosate in patients with
      Alzheimer's disease.

PMID- 16801993
TI  - Atrasentan: a rationally designed targeted therapy for cancer.
AB  - Endothelin axis deregulation triggers a series of events that ultimately
      activates proliferation, invasion, escape from programmed cell death, new vessel
      formation, abnormal osteogenesis and alteration of nociceptive stimuli.
      Atrasentan is a novel agent that effectively targets this pathway and is able to
      inhibit and/or reverse several of these events. Biologic and clinical activity in
      patients with prostate cancer have been demonstrated in a phase III, placebo
      controlled setting by the suppression of markers of biochemical prostate cancer
      progression and a delay in time to disease progression. Atrasentan may represent
      a therapeutic option in the management of prostate and other cancers that is
      worthy of continued investigation.

PMID- 16801994
TI  - Pentavalent human-bovine reassortant rotavirus vaccine: a review of its efficacy
      and safety in preventing acute rotavirus gastroenteritis in healthy infants.
AB  - Acute rotavirus gastroenteritis can be successfully managed with oral and
      intravenous rehydration solutions; however, it is still a major cause of
      childhood mortality and morbidity in developing countries and is responsible for
      significant morbidity and health-care costs in developed countries. Pentavalent
      human-bovine rotavirus vaccine (HBRV) is an oral vaccine containing five live
      attenuated human-bovine reassortant strains containing the human serotypes
      responsible for the majority of rotavirus cases worldwide. Approximately three
      quarters of all acute rotavirus gastroenteritis cases and almost all cases of
      severe gastroenteritis were prevented by pentavalent HBRV in a phase III clinical
      trial. Pentavalent HBRV has a favorable safety profile, with fever, irritability,
      vomiting and diarrhea generally reported in similar proportions of infants who
      received either vaccine or placebo. Results from a large phase III study indicate
      that there was no excess risk of intussusception among those vaccinated compared
      with placebo recipients. This review summarizes the current data on the clinical
      efficacy and safety of HBRV in healthy infants.

PMID- 16801995
TI  - A new combination vaccine for measles, mumps, rubella and varicella.
AB  - ProQuad is a recently approved combination vaccine for simultaneous vaccination
      against measles, mumps, rubella and varicella in children aged 12 months to 12
      years. It combines two well-established vaccines: Measles, Mumps, Rubella Virus
      Vaccine Live (M-M-R II) and Varicella Virus Vaccine Live (Varivax with higher
      varicella-zoster titer). Whereas vaccination against measles, mumps and rubella
      has almost 100% coverage, vaccination against varicella shows a significantly
      lower uptake of approximately 84%. Clinical studies on the immunogenicity and
      efficacy of ProQuad demonstrated seroconversion rates and a magnitude of antibody
      response similar to those observed after administration of its individual
      components, M-M-R II and Varivax vaccines. The incidence of local side effects
      (pain/tenderness/soreness, erythema, swelling, ecchymosis and rash) and systemic
      adverse effects (fever, irritability, rash, upper respiratory infection, viral
      exanthema and diarrhea) is similar to or lower than that observed in component
      vaccines. ProQuad is a highly immunogenic combination vaccine with a good safety
      profile. The use of ProQuad combination vaccine will simplify immunization
      delivery by providing protection against more diseases with fewer injections and
      less pain, improve timely vaccination coverage and reduce the health-care costs
      for additional health visits. The ProQuad combination vaccine facilitates
      implementation of varicella vaccination into routine childhood immunization
      schedules and will help to protect children against these four potentially
      serious diseases.

PMID- 16801996
TI  - Role of current and emerging antithrombotics in thrombosis and cancer.
AB  - In the nearly 130 years since Trousseau first described migratory
      thrombophlebitis in cancer patients, thromboembolism has become a well
      established presenting sign and complication of cancer. The coagulation system is
      activated in cancer and is further amplified by treatment with chemotherapy,
      radiation or surgery. Hypercoagulation is documented in virtually all cancer
      types, albeit at different rates, and is the second leading cause of death in
      cancer patients. The relationship between clotting activation and carcinogenesis
      supports the view of cancer as a hypercoagulable state and holds implications for
      the development of thrombosis, enhancement of tumor growth and risk of poor
      clinical outcomes. Although it is well recognized that cancer can activate the
      coagulation cascade, it is less well known that activation of the coagulation
      system may also support tumor progression. Additionally, platelet activation in
      cancer patients and its impact on tumor progression and metastasis further expand
      the role of the hemostatic system in malignancy. The problem of thrombosis in
      patients with metastatic diseases is a serious concern for clinicians. This
      review explores the mechanisms and clinical implications of coagulation and
      platelet activation in cancer. The prevention and treatment of venous
      thromboembolism in cancer will also be discussed by reviewing data from key
      clinical investigations. Finally, the emerging role of low-molecular-weight
      heparin as an antineoplastic agent will be explored. Warfarin and unfractionated
      heparin have been in clinical use for more than 50 years. Both are effective
      anticoagulants, but their use is associated with a number of impediments,
      including the need for intensive coagulation monitoring, wide variation in dose
      response relationships, multiple drug interactions (in the case of warfarin), and
      serious immune-mediated thrombocytopenia (in the case of heparin). The
      introduction of low-molecular weight heparin advanced anticoagulation therapy by
      enhancing efficacy and eliminating the need for intensive coagulation monitoring.
      Fondaparinux, the first selective factor Xa inhibitor, represents yet another
      improvement in anticoagulation therapy. By binding rapidly and strongly to
      antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes
      specifically the inhibition of factor Xa, which results in effective and linear
      dose-dependent inhibition of thrombin generation. Additionally, efficient
      inhibition of factor Xa activity impairs the activation of tissue factor/factor
      VIIa complex leading to downregulation of procoagulant state, pro-angiogenesis,
      and proinflammatory factors induced by tissue factor/factor VIIa. Furthermore, a
      number of orally active direct antithrombin and anti-factor Xa are in advanced
      clinical development for various thromboembolic disorders.

PMID- 16801998
TI  - Treating the right patient at the right time: Access to cardiac catheterization,
      percutaneous coronary intervention and cardiac surgery.
AB  - The Canadian Cardiovascular Society Access to Care Working Group was formed with
      a mandate to use the best science and information available to establish
      reasonable triage categories and safe wait times for common cardiovascular
      services and procedures through a series of commentaries. The present commentary
      discusses the rationale for access benchmarks for cardiac catheterization and
      revascularization procedures for patients with stable angina, and access
      benchmarks for cardiac catheterization and surgery for patients with valvular
      heart disease. Literature on standards of care, wait times and wait list
      management was reviewed. A survey of cardiac centres in Canada was performed to
      develop an inventory of current practices in identifying and triaging patients.
      The Working Group recommends the following medically acceptable wait times for
      access to cardiac catheterization: 14 days for symptomatic aortic stenosis and
      six weeks for patients with stable angina and other valvular disease. For
      percutaneous coronary intervention in stable patients with high-risk anatomy,
      immediate revascularization or a wait time of 14 days is recommended; six weeks
      is recommended for all other patients. The target for bypass surgery in those
      with high-risk anatomy or valve surgery in patients with symptomatic aortic
      stenosis is 14 days; for all others, the target is six weeks. All stakeholders
      must affirm the appropriateness of these standards and work continuously to
      achieve them. There is an ongoing need to continually reassess current risk
      stratification methods to limit adverse events in patients on waiting lists and
      assist clinicians in triaging patients for invasive therapies.

PMID- 16801999
TI  - Presentation, management and outcomes of thrombosis for children with
      cardiomyopathy.
AB  - BACKGROUND: Thrombosis in children with dilated and inflammatory cardiomyopathy
      is an unpredictable complication with potentially important morbidity. OBJECTIVE:
      To determine the prevalence, associated factors, management and outcomes of
      thrombosis in this setting. METHODS: Data were obtained from review of medical
      records. Factors associated with thrombosis and the impact on outcome were
      sought. RESULTS: From 1990 to 1998, 66 patients that presented with dilated
      cardiomyopathy were followed for a median interval of 1.4 years (range 0 to 9.79
      years) from first presentation. Thrombosis was diagnosed in four patients at
      presentation and in four patients during follow-up. Thrombosis was noted in one
      additional patient at examination after death. The overall nine-year period
      prevalence of thrombosis was 14%. Anticoagulation was started at presentation in
      31% of patients. The mean left ventricular ejection fraction at presentation was
      significantly lower in those given anticoagulation (19+/-8%) versus those who
      were not (32+/-15%; P < 0.001). The mean ejection fraction at presentation was
      similar in those patients with (25+/-10%) versus those without thrombosis (28+/
      15%; P = 0.44). During follow-up, 11 patients died and seven underwent cardiac
      transplantation. Kaplan-Meier estimates of freedom from death or transplantation
      were 88% at three months, 81% at one year and 70% at five years. Survival free of
      transplantation was not affected by thrombosis. CONCLUSIONS: Thrombosis is common
      in children with cardiomyopathy, can occur at any time in the patients' clinical
      course and is not related to clinical features or survival free of
      transplantation. The relevance and prevention of thrombosis in this setting
      remains unclear.

PMID- 16801997
TI  - Non ST segment elevation acute coronary syndromes: A simplified risk-orientated
      algorithm.
AB  - Non-ST segment elevation acute coronary syndromes (NSTE ACS) include a clinical
      spectrum that ranges from unstable angina to NSTE myocardial infarction.
      Management goals aim to prevent recurrent ACS and improve long-term outcomes by
      choosing a treatment strategy according to an estimate of the risk of an adverse
      outcome. Recent registry data suggest that patients with NSTE ACS frequently do
      not receive recommended treatment, and that risk stratification is not used to
      determine either the choice of treatment or the speed of access to coronary
      angiography. The present article evaluates the evidence for recommended treatment
      using information from recent trials and guidelines published by the major
      cardiac organizations in Europe and North America. Using this information, a
      multidisciplinary group developed a simplified algorithm that uses risk
      stratification to select an optimal early management strategy. Long-term outcomes
      are improved by a multi-faceted vascular protection strategy that is initiated at
      the time of hospitalization for NSTE ACS.

PMID- 16802001
TI  - A cost comparison of off-pump CABG versus on-pump CABG at one-year: The Canadian
      off-pump CABG registry.
AB  - BACKGROUND: Evidence suggests that off-pump coronary artery bypass graft surgery
      (CABG) is as safe and effective as on-pump CABG, and the cost of initial
      hospitalization for off-pump CABG is less expensive than on-pump CABG. However,
      it is uncertain whether the cost savings are sustained over a longer period of
      time. OBJECTIVE: To assess in-hospital and one-year direct medical costs of off
      pump CABG versus on-pump CABG in the context of the Canadian health care system.
      METHODS AND RESULTS: From March 2001 to December 2002, 1657 consecutive patients
      enrolled in the Canadian Off-Pump CABG Registry were compared with 1693
      consecutive on-pump patients from Hamilton Health Sciences CABG database. At one
      year, patients of both groups were followed by telephone interview. An economic
      analysis was conducted from the perspective of the Ontario Ministry of Health and
      Long-Term Care, and the data analysis was based on propensity score-matched
      registry patients (1233 pairs) to ensure the comparability of the two study
      groups. Clinical event and resource use information was collected from all
      patients. Unit costs from the Hamilton Health Sciences case-costing system were
      used to estimate hospital costs; all costs were reported in 2003 Canadian
      dollars. Sensitivity analyses were performed to account for uncertainties. The
      cost of initial hospitalization for off-pump CABG was significantly less than on
      pump CABG (11,744 dollars versus 13,720 dollars, P < 0.001). Although follow-up
      costs were similar between the groups, the one-year total cost per patient for
      off-pump CABG remained significantly less than on-pump CABG (12,063 dollars
      versus 14,141 dollars, P < 0.001). CONCLUSION: Off-pump CABG offers significant
      savings during initial hospitalization that are also sustained after one year.

PMID- 16802002
TI  - Profound regression of coronary atherosclerosis with statins.

PMID- 16802000
TI  - Coronary artery disease progression is associated with C-reactive protein and
      conventional risk factors but not soluble CD40 ligand.
AB  - BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide.
      Epidemiological studies have documented conventional risk factors; however, no
      studies to date have addressed the roles of soluble CD40 ligand (sCD40L) and
      monocyte chemoattractant protein-1 (MCP-1), and there have been few reports on
      other novel risk factors in CAD progression. The aim of the present study was to
      explore the roles of novel and conventional risk factors in CAD progression.
      METHODS: Patients with stable angina pectoris who underwent repeat coronary
      angiograms and had serum samples at the time of their first catheterization
      between March 1999 and January 2004 were enrolled. Those who had progression of
      coronary atherosclerosis were classified into the progression group (n = 66).
      Those who did not have CAD progression were classified into the nonprogression
      group (n = 124). RESULTS: There were more cases of diabetes mellitus (36% versus
      20%; P = 0.024) and more men (92% versus 81%; P = 0.040) in the CAD progression
      group than in the nonprogression group, respectively. The progression group also
      had poorer lipid profiles than the nonprogression group, including higher total
      cholesterol (188+/-42 mg/dL versus 173+/-39 mg/dL, respectively; P = 0.014) and
      low density lipoprotein cholesterol (122+/-38 mg/dL versus 112+/-36 mg/dL,
      respectively; P = 0.025). In terms of inflammatory markers, progression patients
      had higher baseline high-sensitivity C-reactive protein (hs-CRP) concentrations
      (P = 0.018), which was also related to the subsequent angiographic severity score
      changes; however, sCD40L (6182+/-4352 pg/mL versus 6244+/-4602 pg/mL; P = 0.961),
      MCP-1 (427+/-540 pg/mL versus 341+/-128 pg/mL; P = 0.580) and adhesion molecules
      concentrations were indifferent between the progression group and the
      nonprogression group, respectively. Using a multivariate logistical regression
      model, the ORs for predicting progression were 2.19 for diabetes mellitus, 2.04
      for hypercholesterolemia and 1.52 for hs-CRP (P < 0.05). CONCLUSION: In the
      present study, only conventional risk factors, and particularly hs-CRP, were
      markers for predicting CAD progression. Novel risk factors, such as
      concentrations of sCD40L, MCP-1 and adhesion molecules, did not play significant
      roles.

PMID- 16802003
TI  - New perspectives on the role of the intestinal flora in health and disease.

PMID- 16802004
TI  - Trends of mortality rates from gastric cancer and colorectal cancer in Romania,
      1955-2003.
AB  - BACKGROUND: Steady and persisting falls in gastric cancer (GC) mortality rates
      have been observed worldwide in the last 50 years, and in Romania too. Colorectal
      cancer (CRC) is presently the most frequent digestive neoplasia in the Western
      countries. An increase of CRC incidence and mortality rates has been reported
      recently in Eastern European countries, including Romania. METHODS: Mortality
      data from GC and CRC, derived from population based mortality statistics, have
      been available on a national scale for 1955-2003. The data were identified from
      the statistics of the Ministry of Health (Bucharest, Romania) and of IARC/OMS
      (Lyon, France). GC and CRC mortality rates global and/or per gender were
      registered by time intervals. After 1995, only data on general mortality rates
      were available. RESULTS: Between 1955-59 and 1990-92, GC mortality rates/100,000
      decreased from 33.14 to 17.70 in males and from 18.77 to 7.00 in females. Between
      1995 and 2003, general mortality rates/100,000 from GC remained stable (17.54 and
      17.74, respectively). Between 1955-59 and 1990-92, CRC mortality
      rates/100,000/gender increased from 4.65 to 10.10 in males and from 4.57 to 7.40
      in females. Between 1995 and 2003, CRC general mortality rates/100 000 increased
      from 14.90 to 19.20. CONCLUSIONS: Our study reports opposite trends in GC and CRC
      mortality rates in the period under study, with GC declining and CRC increasing.
      A male predominance was registered in both neoplasms under study, more obvious in
      GC (male/female ratio: 2-3/1) than in CRC (male/female ratio: 1.5/1).

PMID- 16802005
TI  - Steatosis in hepatitis C virus infection. Response to anti-viral therapy.
AB  - BACKGROUND: Steatosis is a frequent feature of hepatitis-C-virus (HCV) infection.
      Steatosis may be an important cofactor in both accelerating fibrosis and
      increasing liver necroinflammatory activity in chronic hepatitis C. Several
      studies suggested that steatosis induces resistance to interferon and ribavirin
      combination treatment. AIM: to assess the prevalence of steatosis in chronic HCV
      infection and the host factors associated with steatosis, to estimate the impact
      of steatosis on liver fibrosis, and to evaluate the response to antiviral therapy
      in patients with HCV-infection and steatosis. MATERIAL AND METHOD: A
      retrospective study was performed on 37 patients with chronic active HCV
      infection treated with interferon and ribavirin: 21 women and 16 men, mean age
      46.97 years. Presence of metabolic syndrome was assessed according to the ATPIII
      criteria. Cobas Amplicor HCV-Test was used to detect HCV-RNA. Steatosis was
      graded using the Brunt system. RESULTS: Prior to the antiviral treatment,
      steatosis was present in 26 out of 37 patients (70%). Patients with steatosis
      were older, especially those with associated metabolic syndrome. Fibrosis stage
      was significantly advanced in patients with steatosis. Lower baseline viremia
      correlated with sustained response both in patients with and without steatosis.
      Absence of baseline steatosis was associated with higher biochemical and
      virological sustained response. None of the patients with metabolic syndrome had
      a sustained response to antiviral therapy. In all patients, the stage of fibrosis
      did not significantly improve 6 months after cessation of the antiviral
      treatment. CONCLUSION: Steatosis is a frequently encountered histological feature
      in chronic HCV-infection. It is associated with older age, lower virologic
      response and worsening fibrosis irrespective of antiviral treatment.

PMID- 16802006
TI  - Comparative study concerning the efficacy of Peg-IFN alpha-2a versus Peg-IFN
      alpha-2b on the early virological response (EVR) in patients with chronic viral C
      hepatitis.
AB  - BACKGROUND: Pegylated interferons (Peg-IFNs) represent, in association with
      Ribavirin, the first line of treatment in chronic C viral hepatitis. The AIM of
      our paper was to compare the efficacy of Peg-IFN alpha 2a (Pegasys) and Peg-IFN
      alpha 2b (PegIntron) in a group of patients from the Department of
      Gastroenterology in Timisoara. MATERIAL AND METHOD: 116 patients with chronic C
      viral hepatitis were treated. The patients were randomized in chronological order
      (1:1), so that 58 patients were treated with Peg-IFN alpha 2a 180 microg/kg/week
      + Ribavirin (group 1) and 58 were treated with Peg-IFN alpha 2b 1.5
      microg/kg/week + Ribavirin (group 2). Ribavirin was administered in the
      recommended doses, according to weight. The mean age was: group 1 -- 49.3 years,
      group 2 -- 50.9 years (p=0.37). Group 1 consisted of 37 women and 21 men and
      group 2 of 44 women 14 men (p=0.22). In group 1, 48 patients were naive (N1), 7
      were relapsers after previous treatment (RL1) and 3 non-responders to previous
      treatment (NR1). In group 2, 33 patients were naive (N2), 18 relapsers (RL2) and
      7 non-responders (NR2). After 12 weeks of treatment we evaluated the early
      virological response (EVR), defined as a drop in the viral load with 2 logs
      compared to the baseline viremia. RESULTS: The following EVR rates were found: in
      group 1 (Pegasys) - 82.2% (48/58); in group 2 (PegIntron) -- 67.2% (39/58)
      (p=0.08). There were also no significant statistical differences between the
      response rates in the subgroups: naive patients [89.6% vs. 75.2%, p = 0.61],
      relapsers [57.1% vs. 66.6%, p = 0.67] and non responders [33.3% vs. 28.6%, p =
      1]. CONCLUSION: Our head to head comparative study showed that there are no
      statistically significant differences in the EVR between the patients treated
      with Peg-IFN alpha 2a and Peg-IFN alpha 2b.

PMID- 16802008
TI  - Preoperative noninvasive EUS evaluation in patients with esophageal cancer
      considered for esophagectomy.
AB  - BACKGROUND: Worldwide, esophageal cancer ranks fifth in the mortality rate
      regarding tumor locations. EUS is an essential tool in the evaluation of these
      patients allowing accurate staging and permitting stratified treatment options.
      AIM. We have studied prospectively the impact of EUS in the evaluation and
      decision for therapy of patients with esophageal cancer diagnosed in our center.
      MATERIAL AND METHODS: From March 2001 through March 2006, 220 patients were
      hospitalized at the Center of Gastroenterology and Hepatology, Fundeni Clinical
      Institute, with the diagnosis of esophageal cancer. Out of the 220 patients, 41
      patients, with no major comorbidities contraindicating esophagectomy already
      having been screened by abdominal and thoracic CT to disclose distant metastases,
      had EUS with the definite purpose of staging esophageal carcinoma and selecting
      adequate therapy. Assuming that without preoperative staging by EUS, all 41
      patients in the study group would have been offered surgical treatment, we
      evaluated the number of patients and the modality in which EUS resulted in
      changes to the therapeutic plan. RESULTS: Depth of invasion was recorded for the
      41 patients as follows: T1 in 2 patients (4.9%), T2 in 6 patients (14.6%), T3 in
      24 patients (58.5%), and T4 in 10 patients (22%). Regional lymph node (N) status
      as determined by EUS criteria was as follows: N0 in 7 patients (17%) and N1 in 34
      patients (83%). Assessment of distant metastases (M) was recorded showing 4
      patients with celiac axis lymph nodes metastases (M1). Preoperative EUS staging
      changed the decision for surgery in 18 of 41 patients (44%) (p<0.0001) and
      allowed primary esophagectomy in only 6 patients (15%) (p<0.0001). Compared to
      histopathology, the overall accuracy of EUS staging for pT1 and pT2 was 80% for
      staging pT3 and pT4 77% and for lymph node evaluation was approximately 75%.
      CONCLUSION: Esophageal EUS offers useful information to clinicians caring for
      patients with esophageal cancer, impacts clinical decision making, and should be
      used in appropriate settings to plan patients' care.

PMID- 16802007
TI  - Molecular analysis of A1AT (S and Z) and HFE (C282Y and H63D) gene mutations in
      Egyptian cases with HCV liver cirrhosis.
AB  - BACKGROUND: Alpha-1-antitrypsin (A1AT) S and Z deficiency alleles and
      hemochromatosis (HFE) mutant C282Y, H63D alleles were reported to potentially
      affect the liver even if present in a heterozygous state. OBJECTIVES: This is a
      cross-sectional, randomized, case controlled study for evaluation of the
      frequency of these alleles in Egyptian patients with HCV liver cirrhosis and of
      their association with the disease. SUBJECTS: This study included 48 cases with
      viral C cirrhosis recruited from the Hepatology Unit, Mansoura University
      Hospital, Egypt, and 70 unrelated healthy controls. METHODS: PCR amplification of
      relevant gene segment followed by restriction enzyme digestion Taq1 for detection
      of A1AT gene S and Z alleles, digestion with Rsa I and Bcl I for HFE gene C282Y
      and H63D alleles. These alleles were then characterized through analysis of
      resulting restriction fragment length polymorphism (RFLP). RESULTS: Both
      heterozygous (MS) and homozygous (SS) genotypes were significantly more frequent
      in cases than in controls ( P<0.05, RR= 2.23 and 2.17 respectively). Gene
      frequency of S allele was higher in cases than controls (P<0.05, RR=2.17).
      Homozygosity (ZZ) genotype, present only in cases (6.3% vs 0.0% in controls,) did
      not reach statistical significance. HFE gene heterozygosity for H63D allele was
      detected in 20.0% of cases and 21.4% of controls, whereas C282Y allele was
      detected neither among cases nor in controls. CONCLUSION: The presence of the
      relatively high frequency of A1AT S and HFE H63D allele carriers in Egyptian
      cases of HCV liver cirrhosis suggest the necessity to implement routine molecular
      analysis of these genes for detection of risk genotypes among affected families.

PMID- 16802009
TI  - Lateral subcutaneous internal sphincterotomy in the treatment of chronic anal
      fissure: our experience.
AB  - BACKGROUND: Chronic anal fissure is the most common cause of anal pain associated
      with internal anal sphincter hypertonia. Reduction of hypertonia favours fissure
      healing. Temporary reduction in sphincter tone can be achieved by conservative
      treatment. Surgical sphincterotomy achieves permanent reduction of sphincter
      hypertonia and is very successful at healing anal fissures, but requires an
      operation with associated small morbidity. METHODS: A study was undertaken on 246
      patients (120 men, 126 women, mean age 48.3 years), undergoing subcutaneous
      lateral internal sphincterotomy for a chronic fissure-in-ano from January 1, 1981
      to December 31, 2004. Therapeutical outcome, postoperative course and early and
      long-term results were recorded. RESULTS: During the study period, the 246
      patients underwent total subcutaneous lateral internal sphincterotomy, 62 of them
      under general anesthesia (1981-1991), and the remainder under local anesthesia.
      Two-hundred-forty-two patients returned for their postoperative visits at 2, 6,
      24 and 48 weeks, while four patients were lost to follow-up. At 3 months
      postoperatively, 97.5% of fissures had healed; 224 fissures were healed by 6
      weeks, 10 by 7 weeks and 2 by 3 months. Pain was significantly reduced in all
      patients at Day 1 postoperative. Minor complications included hematoma (0.8%) and
      pain (0.4%). New minor incontinence was seen in 7.02% of patients at 48-week
      follow up. Patients' satisfaction was 91.7%. CONCLUSIONS: Total subcutaneous
      internal sphincterotomy is a safe and effective treatment for chronic anal
      fissures, that only rarely impairs continence to flatus.

PMID- 16802010
TI  - Noninvasive biochemical markers of liver fibrosis.
AB  - The assessment of liver fibrosis provides useful information not only for
      diagnosis but also for therapeutic decision. Although needle biopsy of the liver
      is the gold standard for fibrosis assessment, it has some technical limitations
      and risks. This has led to the development of noninvasive biochemical markers of
      liver fibrosis: direct markers which reflect extracellular matrix turnover and
      indirect markers which reflect alterations in hepatic function. Markers
      associated with matrix deposition or degradation and some cytokines implied in
      fibrosis may be used as individual markers or as combination of markers to
      generate an algorithm to evaluate the stage of fibrosis. Also, fibrosis may be
      predicted by using indirect markers as a single routine laboratory test or
      multicomponent indirect fibrosis tests. Serum markers are of great value not only
      in patients at risk for liver biopsy, but also as a part of the assessment of
      patients with chronic liver disease avoiding the invasive methods.

PMID- 16802011
TI  - Endoscopic ultrasound elastography-- a new imaging technique for the
      visualization of tissue elasticity distribution.
AB  - Endoscopic ultrasound (EUS) elastography is an imaging procedure used for the
      visualization of tissue elasticity during usual EUS examinations. EUS
      elastography can be accomplished real-time with state-of-the-art ultrasound
      systems, with the images being represented in transparent color superimposed on
      the conventional gray-scale B-mode scans. The aim of this review was to introduce
      the potential range of applications of EUS elastography. EUS elastography might
      be useful for the differentiation of benign and malignant lymph nodes, with a
      qualitative pattern analysis and a quantitative histogram analysis of the color
      images being used to adequately classify the lesions. Mapping of the tissue
      elasticity distribution might be useful for the differential diagnosis of focal
      pancreatic masses, especially in the setting of chronic pancreatitis where the
      accuracy of EUS-guided fine needle aspiration is also low. EUS elastography might
      also enhance the detection and differentiation of various solid tumors (adrenal
      tumors, submucosal tumors, etc.) situated nearby the gastrointestinal tract.
      Routine use of EUS elastography thus offers supplemental information that
      enhances conventional EUS imaging, with a possible decrease in the number of un
      necessary EUS-FNA procedures used for tissue confirmation. However, future
      enhancements of the EUS elastography technology, as well as prospective,
      randomized studies will probably establish the clinical impact of dynamic
      elasticity imaging.

PMID- 16802012
TI  - Long-lasting effect of endoscopic dilatation of an esophageal stenosis due to
      eosinophilic esophagitis.
AB  - Eosinophilic esophagitis is a rare disorder mainly affecting pediatric patients,
      although the number of cases reported in adults, especially young males with
      dysphagia, is on the increase. The most severe complication is esophageal
      stenosis. We report the case of a 26 year old white male who presented with
      dysphagia in 2001. Endoscopy revealed an esophageal stenosis 35 cm aboral without
      signs of mucosal inflammation, that was dilated once. The patient was
      asymptomatic until 2004, when he presented again with dysphagia. Eosinophilic
      esophagitis was diagnosed. Dilatation was repeated. The further clinical course
      was uneventful with no more episodes of dysphagia.

PMID- 16802013
TI  - A rare form of isolated mesenteric Castleman's disease presenting as an abdominal
      mass (isolated mesenteric Castleman's disease).
AB  - Castleman's disease is a rare disorder characterized by proliferation of the
      lymphoid tissue. The most frequent location of the disease is the mediastinum.
      The location of the disease in the mesentery is rare and it is usually associated
      with the generalized form of the disease. We report a case of a 22-year old woman
      with isolated mesenteric Castleman's disease of the lymphoid variant, which
      presented as a palpable abdominal mass. The final diagnosis was reached after
      exploratory laparotomy and resection of the tumor. The described case is the
      first reported case of Castleman's disease of the lymphoid subtype, located in
      the mesentery.

PMID- 16802014
TI  - Pyloric stenosis as a presenting symptom of Crohn's disease.
AB  - We report a rare case of pyloric stenosis as a presenting symptom of Crohn's
      disease. Clinical improvement and long-term relief of pyloric obstruction were
      obtained following a short course treatment of corticostroids and total
      parenteral nutrition. In contrast to most of the cases described previously in
      the literature, surgical treatment was not required.

PMID- 16802015
TI  - Minimally invasive esophagectomy by video-assisted thoracoscopic approach for
      esophageal carcinoma. A case report.
AB  - Esophageal carcinoma represents a pathological entity with a bad prognosis even
      if adequate multimodal treatment is applied. Because of the high operative
      morbidity and mortality, due especially to respiratory and infectious
      complications, the tendency nowadays is to mobilize the thoracic esophagus and to
      perform esophagectomy and mediastinal lymphadenectomy by thoracoscopy instead of
      thoracotomy. We present the case of a 55-year-old male patient who was diagnosed
      with a mediothoracic esophageal spinocellular carcinoma, in whom we successfully
      performed subtotal esophagectomy by cervico-thoraco-abdominal approach, the
      dissection of the thoracic esophagus being performed entirely by thoracoscopy.

PMID- 16802016
TI  - Congenital diaphragmatic hernia as a cause of cardiorespiratory failure and
      visceral obstruction in late pregnancy.
AB  - BACKGROUND: Diaphragmatic hernia complicating pregnancy is rare and results in a
      high mortality rate, particularly if early surgical intervention is not
      undertaken. CASE PRESENTATION: A woman at 23 week gestation was admitted with
      symptoms of respiratory failure and bowel obstruction due to incarceration of
      viscera through a left posterolateral defect of the diaphragm (Bochdalek's
      hernia). Surgery (left thoracoabdominal incision) demonstrated compression
      atelectasis, mediastinal shift, strangulation and gangrene of the herniated
      viscera which led to segmental resection of the involved portion of large
      intestine with re-establishment of bowel continuity by end to end anastomosis.
      The greater omentum was partly necrotic necessitating resection. The
      diaphragmatic defect was closed with interrupted sutures. Postoperative period
      was uncomplicated. Pregnancy was allowed to continue until 39 weeks' gestation at
      which time elective cesarean delivery was performed. CONCLUSION: Symptomatic
      maternal diaphragmatic hernia during pregnancy is a surgical emergency and
      requires a high index of suspicion.

PMID- 16802017
TI  - Ultrasonography contribution to the detection and characterization of hepatic
      restructuring: is the "virtual biopsy" taken into consideration?
AB  - Generally, the evolution of diffuse liver diseases is variable but quite long.
      Even the severe types of chronic hepatitis have a slow progression which implies
      decades, often over 20-30 years. Cirrhosis is the principal long time
      complication of chronic hepatopathies. It represents a major risk factor for the
      development of hepatocellular carcinoma. Ultrasonography plays an important role
      among the methods used for detecting diffuse liver diseases, for placing them and
      identifying supplementary risk factors for carcinogenesis and of hepatocellular
      carcinoma itself. The two- and especially the three-dimensional exploration allow
      the characterization of hepatic texture and the identification of certain changes
      which may suggest hepatic restructuring.

PMID- 16802019
TI  - Synchronous gastric adenocarcinoma and carcinoid.

PMID- 16802020
TI  - Asymptomatic achalasia mimicking a mediastinal mass.

PMID- 16802021
TI  - Richard Compton, University of Oxford.
AB  - The Analyst profiles Richard Compton, Professor of Chemistry at the University of
      Oxford and the first and only recipient of both the RSC Medals in
      Electrochemistry and in Electroanalytical Chemistry.

PMID- 16802022
TI  - Solid-supported room temperature phosphorescence from aflatoxins for analytical
      detection of Aspergillus spp. strains.
AB  - A simple, direct and rapid analytical methodology for the detection of aflatoxin
      producing Aspergillus spp. strains based on the measurement of room temperature
      phosphorescence from aflatoxins is presented here.

PMID- 16802023
TI  - Capacitance immunosensors based on an array biotape.
AB  - A new array immunosensing system with high-throughput has been developed, based
      on the principle of a biotape that could be used to make a biocassette recorder.

PMID- 16802024
TI  - A simplified multidimensional approach for analysis of complex biological
      samples: on-line LC-CE-MS.
AB  - Information on protein expression, disease biomarkers or surrogate markers and
      genetic disorders can nowadays be achieved from analysis of complex biological
      samples by liquid separation coupled to mass spectrometric (MS) detection. This
      paper describes fast multidimensional separation by on-line liquid chromatography
      (LC) and capillary electrophoresis (CE), followed by electrospray ionization
      (ESI) Fourier transform ion cyclotron resonance (FTICR) MS detection. This
      detector provides ultrahigh resolution of the detected ions, mass accuracy at the
      ppm-level and high sensitivity. Most of the challenge of this system lies in the
      development of a new interface for the on-line coupling of LC to CE. The
      interface developed in poly(dimethylsiloxane) provides a RSD for injection
      repeatability of <3.5% and surface control for unspecific binding by deactivation
      with a cationic polymer, PolyE-323. We have evaluated the interface, as well as
      the overall system, with respect to robustness and deconvolution ability.
      Sequence coverage for bovine serum albumin (BSA) of 93% showed a high recovery of
      sample in the different transfer steps through the system. The detection limit
      for identification is 277 ng mL(-1) (or 280 nM) on average for peptides. In the
      future, we expect LC-CE-MS to be a novel strategy for elucidating the chemistry
      of biological matrices.

PMID- 16802025
TI  - Immobilization of proteins on agarose beads, monitored in real time by bead
      injection spectroscopy.
AB  - A novel approach to real-time monitoring of protein immobilization resulted in
      the surprising finding that current immobilization protocols are far from
      optimized.

PMID- 16802026
TI  - Bead injection for biomolecular assays: Affinity chromatography enhanced by bead
      injection spectroscopy.
AB  - Selective capture of target biomolecules by ligands immobilized on a solid
      support is a cornerstone of two seemingly unrelated techniques: micro-Affinity
      Chromatography (microAC) and micro-Bead Injection Spectroscopy (microBIS). This
      work shows, for the first time, how these techniques can be carried out using the
      same instrument and how the data obtained this way complement each other,
      yielding complete information on retention and elution of target biomolecules.
      Biomolecular association and dissociation were investigated by microAC and
      microBIS, using computer-controlled programmable flow and the same instrument for
      automated bead transport, packing of a micro-column, assay of the analyte, and
      bead disposal. The absorbance of the analyte was monitored within the fiber optic
      flow cell configured either for monitoring directly on the beads or post-column
      after elution. The separation, binding, and elution of immunoglobulins (human
      IgG, rabbit IgG, and horse IgG) on protein G-coated Sepharose beads were studied
      as model systems. The limit of detection of the microAC technique was determined
      to be 5 ng microL(-1) IgG, and that of the microBIS technique was 50 ng microL(
      1) IgG.

PMID- 16802027
TI  - Needle enzyme electrode based glucose diffusive transport measurement in a
      collagen gel and validation of a simulation model.
AB  - Rapid response needle enzyme electrodes were fabricated to measure the glucose
      concentration at the centre of a cylindrical spiralled collagen gel, which is a
      relevant constituent for tissue engineering scaffolds. The experimental data were
      based on a low consumption glucose sensor which minimised the distorting effect
      of enzymatic degradation. As the measurement was carried out within a collagen
      gel the stirring independence was compulsory for the biosensor. Glucose
      concentration changes were derived from a model based on the solution to Fick's
      Second Law. This had two different expressions for different dimensionless time
      (T) domains. The expression for large T and a first order approximation for small
      T were known. The expression for high order approximation for small T was then
      derived. An analytical expression consisting of fast convergent parts of these
      two expressions is proposed, which operates for the entire time region. A
      computational model for glucose concentration evolution where an electrode is
      located is proposed to operate for extended time periods. The model was confirmed
      by agreement between the simulated and observed data. An experimental technique
      is developed here to determine glucose diffusion coefficient by fitting the
      simulated concentration profile to the observed one. The glucose diffusion
      coefficient within the collagen gel was estimated to be 1.3 x 10(-6) cm(2) s(-1);
      higher accuracy is achieved here because errors due to noise, baseline and zero
      time determination are minimised with best fit.

PMID- 16802028
TI  - Investigation of binding event perturbations caused by elevated QCM-D oscillation
      amplitude.
AB  - We report measurements with the quartz crystal microbalance with dissipation
      monitoring (QCM-D) technique, with focus on how the shear oscillation amplitude
      of the sensor surface influences biorecognition binding events. Technically, this
      is made as reported recently (M. Edvardsson, M. Rodahl, B. Kasemo, F. Hook, Anal.
      Chem., 2005, 77(15), 4918-4926) by operating the QCM in dual frequency mode; one
      harmonic (n = n1) is utilized for continuous excitation of the QCM-D sensor at
      resonance at variable driving amplitudes (1-10 V), while the second harmonic (n
      not equaln(1)) is used for combined f and D measurements. By using one harmonic
      as a "probe" and the other one as an "actuator", elevated amplitudes can be used
      to perturb - or activate - binding reactions in a controlled way, while
      simultaneously maintaining the possibility of probing the adsorption and/or
      desorption events in a non-perturbative manner using combined f and D
      measurements. In this work we investigate the influence of oscillation amplitude
      variations on the binding of NeutrAvidin-modified polystyrene beads (slashed
      circle approximately 200 nm) to a planar biotin-modified lipid bilayer supported
      on an SiO2-modified QCM-D sensor. These results are further compared with data on
      an identical system, except that the NeutrAvidin-biotin recognition was replaced
      by fully complementary DNA hybridization. Supported by micrographs of the binding
      pattern, the results demonstrate that there exists, for both systems, a unique
      critical oscillation amplitude, A(c), below which binding is unaffected by the
      oscillation, and above which binding is efficiently prevented. Associated with
      A(c), there is a critical crystal radius, r(c), defining the central part of the
      crystal where binding is prevented. From QCM-D data, A(c) for the present system
      was estimated to be approximately 6.5 nm, yielding a value of r(c) of
      approximately 3 mm--the latter number was nicely confirmed by fluorescent- and
      dark-field micrographs of the crystal. Furthermore, the fact that A(c) is
      observed to be identical for the two types of biorecognition reactions suggests
      that it is neither the strength, nor the number of contact points, that determine
      the amplitude at which binding is prevented. Rather, particle size seems to be
      the determining parameter.

PMID- 16802029
TI  - Molecularly imprinted on-line solid-phase extraction combined with flow-injection
      chemiluminescence for the determination of tetracycline.
AB  - A molecularly imprinted polymer solid phase extraction (MISPE) method combined
      with flow-injection chemiluminescence (FI-CL) for the determination of residual
      tetracycline (TC) in fish samples is presented. The molecularly imprinted polymer
      (MIP) of TC was synthesized and particles of this MIP were packed into a
      polytetrafluoroethylene (PTFE) tube, which was connected into the sampling loop
      of an eight-way injection valve and served as the MISPE column for on-line
      selective adsorption of TC. The eluent (CH3CN : HNO3 (0.01 mol L(-1)) = 4 ratio
      1, v ratio v) was used for extracting the adsorbed TC, which could be detected by
      its good enhancing effect on the CL reaction between Ce(iv) and rhodamine B. The
      CL intensity is linear to TC concentration in the range from 4 x 10(-9) to 4 x
      10(-7) g mL(-1). The detection limit is 1 x 10(-9) g mL(-1) (3 sigma) and the
      relative standard deviation is 2.4% (n = 9). The conditions of preconcentration,
      extraction and CL reaction were carefully studied. The selectivity experiment
      shows that the selectivity and sensitivity of the CL method could be improved
      greatly when MIP was used as a recognition material in SPE. However, the MISPE
      column interacted indiscriminately with oxytetracycline (OTC) with a 49 +/- 2%
      binding. An intermediate differential pulsed elution (DPE) step using 3% acetic
      acid as eluent was employed to remove OTC and other interfering substances. The
      proposed MISPE-CL method has been applied successfully to the determination of TC
      in fish samples. At the same time, the binding characteristics of the polymer to
      tetracycline were evaluated by batch and dynamic methods.

PMID- 16802030
TI  - Analysis of linear alkylbenzene sulfonate homologues in environmental water
      samples by mixed admicelle-based extraction and liquid chromatography/mass
      spectrometry.
AB  - Hemimicelles and admicelles of cetyltrimethylammonium bromide (CTAB) and
      cetylpyridinium chloride (CPC), adsorbed onto silica, were tested as sorbents for
      the solid phase extraction (SPE) of linear alkylbenzene sulfonate (LAS)
      homologues from environmental water samples. LASs were quantitatively retained on
      both surfactants due to high hydrophobic and ionic interactions, which led to the
      formation of analyte-extractant mixed aggregates. Parameters affecting the SPE of
      LASs were optimised. Recoveries of analytes from wastewater influent and effluent
      and river water samples ranged between 86 and 110%. Combination of SPE with
      liquid chromatography/mass spectrometry provided detection limits for the
      different LAS homologues of about 4 ng L(-1). The precision of the method,
      expressed as relative standard deviation, ranged from 5 to 9%. The method was
      applied to the analysis of LASs in wastewater and river samples using sample
      volumes between 10 and 25 mL. The LAS concentrations found ranged from 9 to 503
      microg L(-1). No cleaning step was required to get accurate results.

PMID- 16802031
TI  - HPLC analysis of functionalized poly(amidoamine) dendrimers and the interaction
      between a folate-dendrimer conjugate and folate binding protein.
AB  - Poly(amidoamine) (PAMAM) dendrimers of different generations with carboxyl,
      acetyl, and hydroxyl terminal groups and a folic acid (FA)-dendrimer conjugate
      were separated and analyzed using reverse-phase high performance liquid
      chromatography (HPLC). Analysis of both the individual PAMAM derivatives and the
      separation of mixed generations can be achieved using a linear gradient 0-50%
      acetonitrile (ACN) (balance water) within 40 min. We also show that PAMAMs with
      defined acetylation and carboxylation degrees can be analyzed using HPLC.
      Furthermore, a generation 5 dendrimer-FA conjugate (G5.75Ac-FA4; Ac denotes
      acetyl) was analyzed and its specific binding with a bovine folic acid binding
      protein (FBP) was monitored. The HPLC and sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) results indicate the formation of three complexes
      after the binding of G5.75Ac-FA4 with FBP. Dendrimers with FA moieties show much
      higher specific binding capability with FBP than those without FA moieties.
      Findings from this study indicate that HPLC is an effective technique not only
      for characterization and separation of functionalized PAMAM dendrimers and
      conjugates but also for investigation of the interaction between dendrimers and
      biomolecules.

PMID- 16802032
TI  - Making "wheels" and "cubes" from triangles.
AB  - [Mn(IV)Mn(II)3] triangular units directed by the presence of tripodal alcohols
      self-assemble in the presence of azide and acetate ligands to form either a
      [Mn24] "wheel" or a [Mn32] "cube".

PMID- 16802033
TI  - Electronic coupling in 1,4-(COS)2C6H4 linked MM quadruple bonds (M = Mo, W): the
      influence of S for O substitution.
AB  - Electronic structure calculations employing density functional theory on the
      compounds [(HCO2)3M2]2(mu-X-C6H4-X) where M = Mo and W and -X = -CO2, -COS and 
      CS2 reveal that the successive substitution of oxygen by sulfur leads to enhanced
      electronic coupling as evidenced by the increased energy separation of the metal
      delta orbital combinations which comprise the HOMO and HOMO-1. This enhanced
      coupling arises principally from a lowering of the LUMO of the X-C6H4-X bridge
      which, in turn, increases mixing with the in-phase combination of the M2 delta
      orbitals. The compounds [(Bu(t)CO2)3M2]2(mu-SOC-C6H4-COS), where M = Mo and W,
      have been prepared from the reactions between M2(O2CBu(t))4 and the
      thiocarboxylic acid 1,4-(COSH)2C6H4 in toluene and the observed spectroscopic and
      electrochemical data indicate stronger electronic coupling of the M2 centers in
      comparison to the closely related terephthalate compounds.

PMID- 16802034
TI  - Syntheses and structures of metal tetrazole coordination polymers.
AB  - Two salts and seven copper(I/II) and silver(I) coordination polymers containing
      tetrazolyl ligands have been hydro(solvo)thermal synthesized by metal salts, NaN3
      and various nitriles generated via [2 + 3] cycloaddition reactions of
      organonitriles and sodium azide. The study also shows that in some cases the
      azide can play a dual role in the in situ syntheses of metal tetrazole complexes,
      namely, starting material for tetrazole ligand and co-ligand in the tetrazole
      based coordination complexes. Compounds and are simple salts of ammonium and
      sodium 5-methyltetrazolate. Compound has a 3-D framework with intersecting
      channel and unprecedented (4(9).6(6)) topology constructed from mixed-valent Cu8
      clusters. Compounds and are isomorphous, and have 3-D organic-inorganic
      frameworks constructed by [M2(mtta)]+ (Hmtta = 5-methyltetrazole) ribbon and
      [M2(N3)]+ (M = Cu, Ag) layer two types of structural motifs, which contains an
      mu(4)-1,1,1,3 azide. Compound is a 3-D four-connected chiral complex with
      (4(2).8(4))(Cu)(4(2).8(2).10(2))(tta) topology. The structure of consists of 2-D
      three-connected layers that are linked by ligand-unsupported Ag(I)...Ag(I)
      interactions to form a 3-D supramolecular array. Compound shows a 3-D chiral
      framework containing tetrahedrally and linearly coordinated Ag(I) ions and mu3-
      and mu4-two types of 5-propyltetrazolate. Compound has a 2-D layered structure
      formed by linkage of [Ag(tetrazolyl)] ribbons via C-C and N-Ag bonds. Magnetic
      measurement confirmed that there are two Cu(II) ions and six Cu(I) ions per Cu8
      unit consistent with a mixed-valent Cu(I,II) complex.

PMID- 16802036
TI  - The chemistry of nitrogen coordinated tertiary carboxamides: a spectroscopic
      study on bis(picolyl)amidecopper(II) complexes.
AB  - Metal coordination of the electrically neutral nitrogen atom of a tertiary
      carboxamide reduces the barrier to C-N-bond rotation and activates the amide
      towards methanolysis. X-Ray crystallographic studies indicate that this
      reactivity is correlated to a lifting of the amide resonance structure and
      concurrent pyramidalization at nitrogen. However, mechanistic data in solution
      have not been obtained. It became evident that structural mobility is
      characteristic of the complexes and the crystallographic data do not fully
      account for relevant reactive species. In this report we summarize IR, UV-vis,
      and EPR spectra of amide nitrogen coordinated bis(picolyl)amide complexes with
      copper(II) triflate and copper(II) chloride. A comparison between spectra sampled
      in the aprotic solvents dichloromethane and acetonitrile, as well as under
      methanolysis conditions reveals the nature of several species formed in solution.
      The key reactions are (I) ligand exchange involving either CH3CN or CH3OH, or, in
      IR experiments, bromide ions from KBr, (II) coordination-dissociation equilibria
      involving the urethane protecting groups of amino acid substituted ligands Boc
      Xaa-bpa (Boc = tert-butoxycarbonyl, Xaa = glycine, alanine, and leucine,
      respectively, bpa = bis(picolyl)amine), (III) dissociation of a chloro ligand
      from LCuCl2 complexes and formation of square-pyramidal complex cations [LCuCl]+,
      and finally (IV) complete dissociation of the polydentate tertiary amide ligand
      to produce free copper ions in solution. Taken together, the results provide a
      fairly detailed qualitative picture of the processes which accompany the amide
      bond methanolysis.

PMID- 16802035
TI  - meso-[{Ru(phen)2}2(mu-HAT)]4+: a high-affinity DNA hairpin probe {HAT =
      1,4,5,8,9,12-hexaazatriphenylene; phen = 1,10-phenanthroline}.
AB  - 1H NMR spectroscopy and fluorescent intercalator displacement (FID) assays have
      been used to investigate the DNA-binding abilities of two series of dinuclear
      polypyridyl ruthenium(II) complexes of the form [{Ru(L)2}2(mu-BL)]4+ {L = 2,2'
      bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (Me2bpy), 1,10-phenanthroline
      (phen), or 4,7-dimethyl-1,10-phenanthroline (Me2phen); BL = 2,2'-bipyrimidine
      (bpm) or 1,4,5,8,9,12-hexaazatriphenylene (HAT)}. Preliminary FID surveys of
      these metal complexes against a variety of different oligonucleotides revealed
      that those complexes based upon the HAT bridging ligand induced greater
      fluorescence decreases in dye-bound DNA than did their bpm-bridged counterparts,
      suggesting a higher binding affinity by the HAT-bridged species. Furthermore, the
      greatest fluorescence decreases were typically observed in an oligonucleotide
      featuring a six-base hairpin loop. The apparent binding affinity of the metal
      complexes was also found to be a function of the stereochemistry and identity of
      the terminal ligands of the complex. The meso (DeltaLambda) stereoisomer
      generally induced greater fluorescence decreases than did either enantiomer
      (DeltaDelta or LambdaLambda), phen-based terminal ligands performed better than
      bpy-based terminal ligands, and those terminal ligands with methyl substituents
      demonstrated stronger apparent binding than did their non-methylated analogues.
      NMR experiments on meso-[{Ru(phen)2}2(mu-HAT)]4+ and meso-[{Ru(Me2phen)2}2(mu
      HAT)]4+ demonstrated that both complexes bound with high affinity to the six-base
      hairpin oligonucleotide at the stem-loop interface and provided evidence to
      support stronger binding by the methylated species. meso-[{Ru(phen)2}2(mu-HAT)]4+
      was found to bind poorly to duplex DNA and smaller four-base hairpin loops in FID
      and NMR experiments, whereas FID data suggest that the methylated analogue binds
      relatively strongly to most oligonucleotide sequences (the four- and six-base
      hairpins in particular). These results demonstrate that binding affinity can come
      at the expense of selectivity, with meso-[{Ru(phen)2}2(mu-HAT)]4+ proving to be
      an efficient compromise between the two as a high-affinity DNA hairpin probe.

PMID- 16802037
TI  - Carbohydrate-metallocene conjugates: selective formation of a
      zirconadioxacyclopentane-type dimer from the reaction of a bis(enolate)ZrCp2
      reagent with a glucofuranoside derivative.
AB  - The zirconocene enolate complex bis(2-propenolato)ZrCp2 (1) reacts with two molar
      equivalents of the 1,2,3,4-O-tetramethyl-alpha-D-glucopyranoside (2) with
      liberation of two equivalents of acetone to yield cleanly the
      bis(carbohydrate)zirconcene complex (3). Alternatively 1 and the "bifunctional"
      glucose derivative 3-O-benzyl-1,2-O-isopropylidene-glucofuranoside (4) react to
      the corresponding zirconadioxacyclopentane-type metallacyclic product that was
      isolated as the respective dimer (5) featuring a sequence of linearly anellated
      five-, four-, five-membered metallacycles. Both carbohydrate zirconocene
      complexes 3 and 5 were characterized by NMR experiments as well as by X-ray
      diffraction.

PMID- 16802038
TI  - Effect of methylation on the coordination of copper by small azacryptands; the
      role of geometrically constrained hydrogen bonding in stabilizing terminally
      coordinated oxygen species.
AB  - Treatment of N-methyl substituted aminocryptand hosts with copper(II) generates
      monocopper(II) cryptates where copper(II) coordinates an oxygen-centered species,
      formally H3O+, which is also strongly hydrogen bonded to three aminocryptand N
      methyl atoms via bonds which may best be viewed as NH(delta+)...O(delta-) in
      consequence of charge transfer. The strength of this hydrogen bonding precludes
      successful competition of another copper ion for the second coordination site
      thus suppressing formation of any Cu-Cu bonded average-valent system.

PMID- 16802039
TI  - The subtle effects of iron-containing metal surfaces on the reductive
      carbonylation of RuCl3.
AB  - The use of iron-containing metal surfaces, Fe, Fe-Cr-alloy and stainless steel,
      for the synthesis of mixed metal Ru-Fe compounds has been studied. The studied
      process was reductive carbonylation of RuCl3 in the presence of a metal surface.
      Reactions were carried out in ethanol solutions under 10-50 bar carbon monoxide
      pressure at 125 degrees C using an autoclave. During the reaction the metal
      surface was oxidized, releasing iron into the solution and acting as a
      sacrificial source of iron. Under these conditions the corrosion of the metal
      surface was facile and produced a series of iron-containing species. In addition
      to the formation of most obvious iron(II) products, such as [Fe(H2O)6]2+ or
      [FeCl2(H2O)4] the use of the metal surface also provided a route to novel labile
      trinuclear [Ru2Cl2(mu-Cl)4(CO)6FeL2] (L = H2O, EtOH) complexes. The stability and
      reactivity of the [Ru2Cl2(mu-Cl)4(CO)6FeL2] complexes were further studied using
      computational DFT methods. Based on the computational results a reaction route
      has been suggested for the formation and decomposition of [Ru2Cl2(mu
      Cl)4(CO)6FeL2].

PMID- 16802040
TI  - Equilibrium and structure of the Al(III)-ethylenediamine-N,N'-bis(3-hydroxy-2
      propionate) (EDBHP) complex. A multi-method study by potentiometry, NMR, ESI MS
      and X-ray diffraction.
AB  - The equilibrium and structure of the complex formed by Al(III) and
      ethylenediamine-N,N'-bis(3-hydroxy-2-propionate) (EDBHP2-) have been studied
      using pH-potentiometry, 1H and 27Al NMR, ESI MS and single crystal X-ray
      diffraction methods. The EDBHP ligand is a strong Al-binder in aqueous solution
      for pH between 4 and 8 and for c(Al) = c(EDBHP)> or = 0.1 mmol dm(-3). The
      dominating complex identified by ESI MS and potentiometry is a neutral dimer,
      Al2L2(OH)2, with logbeta(22-2) = 14.16 +/- 0.03. In the solid
      Al2(EDBHP)2(OH)2.2H2O the Al(III) ions are connected through a double hydroxo
      bridge. Both four-dentate organic ligands are coordinated terminally through two
      carboxylate groups and two N-donors forming three five-membered chelate rings.
      The hydroxyl groups of the ligand EDBHP remain protonated and are not coordinated
      to the aluminium ions. The structure and composition of the dimer are very likely
      the same in solution and the solid state.

PMID- 16802041
TI  - Dinuclear and layered copper 2-pyridylphosphonates with weak ferromagnetism
      observed in layer compound Cu(C5H4NPO3).
AB  - This paper reports the syntheses and structures of three new copper phosphonates
      based on 2-pyridylphosphonate, namely, Cu(C(5)H(4)NPO(3)H)2 (1),
      Cu3(OH)2(C(5)H(4)NPO(3))2.2H2O (2) and Cu(C(5)H(4)NPO(3)) (3). Compound 1 has a
      discrete dimeric structure in which the {CuO(4)N} square pyramids are linked by
      the {CPO(3)} tetrahedra through corner-sharing. The dimers are further connected
      into a chain through hydrogen bonds. In compound 2, edge-sharing {Cu(1)O(4)N}
      square pyramids and {Cu(2)O(4)} planes are found to form an infinite chain with
      composition {Cu(3)(mu-OH)(2)(mu-O)(4)}. Neighboring chains are linked by the
      phosphonate groups of the 2-pyridylphosphonate ligands, resulting in inorganic
      layers containing 4-, 8- and 12-membered rings. The pyridyl groups and the
      lattice water molecules occupy the inter-layer space. In compound 3, the
      {Cu(1)O(4)} and {Cu(2)O(2)N(2)} planes are each corner-shared with the {CPO(3)}
      tetrahedra, forming an inorganic layer containing 8- and 16-membered rings. The
      pyridyl groups reside between the layers. Crystal data for 1: space group P(-)1,
      a = 8.4045(19), b = 8.751(2), c = 10.632(2) A, alpha = 66.673(4), beta =
      72.566(4), gamma = 70.690(4) degrees , V = 664.7(2) A(3), Z = 2. Crystal data for
      2: space group P2(1)/c, a = 7.9544(17), b = 21.579(4), c = 5.0243(10) A, beta =
      105.332(3) degrees , V = 831.7(3) A(3), Z = 2. Crystal data for 3: space group
      P2(1)/c, a = 4.7793(11), b = 15.319(3), c = 8.6022(19) A, beta = 97.156(4)
      degrees , V = 624.9(2) A(3), Z = 4. Magnetic measurements reveal that dominant
      antiferromagnetic interactions are propagated between the copper centers in
      compounds 1-3. For 3, spin canting is observed with a ferromagnetic transition
      occurring at 9 K.

PMID- 16802042
TI  - Synthesis and structural characterization of lanthanide(III) nitrate complexes of
      a tetraiminodiphenol macrocycle in the solid state and in solution.
AB  - The lanthanide(III) complexes [Ln(LH2)(NO3)3] 1-11(La-Er), 15(Y) and
      [Ln(LH2)(NO3)2(H2O)](NO3) 12-14 (Tm-Lu) of the tetraiminodiphenolate macrocycle
      L2- have been prepared by the transmetallation reaction between [Pb(LH2)(NO3)2]
      and Ln(NO3)3.nH2O. In these compounds, the uncoordinated imino nitrogens are
      protonated and are hydrogen bonded to the phenolate oxygens. The X-ray crystal
      structures of the La (1), Ho (10) and Lu (14) compounds have been determined.
      Compounds 1 and 10, in which all the three nitrates are bound in bidentate
      fashion, are isostructural with distorted bicapped square antiprism geometry for
      the metal centre. In [Lu(LH2)(NO3)2(H2O)](NO3) 14, of the two metal bound
      nitrates one is bidentate and the other is unidentate, while the metal centre
      obtains a distorted square antiprism coordination environment. Proton NMR spectra
      of the paramagnetic lanthanide complexes have been studied in detail.
      Contributions of contact and pseudo-contact shifts to the lanthanide induced
      isotropic shifts (LIS) of the macrocycle protons have been separated and good
      agreement has been obtained between the calculated LIS values and the
      experimentally observed values. Analysis of the NMR data has led us to conclude
      that all the complexes in dimethyl sulfoxide solution attain similar
      configurations. The absorption and emission spectral characteristic of several
      compounds have been investigated. The complexes of samarium (5) and europium (6)
      on photoexcitation at 400 nm exhibit well-resolved luminescence spectra at 77 K
      both in the solid state and a methanol-ethanol (1 : 4) glassy matrix. For the
      terbium (8) and dysprosium (9) complexes, however, the observed luminescence
      peaks are less resolved and weak in intensity.

PMID- 16802043
TI  - Weak antiferromagnetic coupling for novel linear hexanuclear nickel(II) string
      complexes (Ni6 12+) and partial metal-metal bonds in their one-electron reduction
      products (Ni6 11+).
AB  - The preparation, crystal structures, magnetic properties and electrochemistry of
      novel linear hexanuclear nickel string complexes (Ni6(12+)) and their
      corresponding 1-e(-) reduction products (Ni6(11+)) are reported. In these
      complexes, the hexanickel chain is in a symmetrical arrangement (approximately
      D(4) symmetry) and is helically supported by four bpyany(2-) ligands [bpyany(2-)
      = the dianion of 2,7-bis(alpha-pyridylamino)-1,8-naphthyridine]. The Ni6(12+)
      complexes show that the two terminal nickel ions have high-spin states (S = 1)
      and the four inner ones have low-spin states (S = 0). The two terminal nickel
      ions exhibit weak antiferromagnetic coupling of ca.-5 cm(-1). All of Ni6(12+)
      complexes display three reversible redox couples at about -0.70, -0.20 and +1.10
      V (vs. Ag/AgCl). The first reduction wave at about -0.20 V suggests facility of 1
      e(-) reduction for the Ni(6)(12+) compounds. The reaction of Ni(6)(12+) complexes
      with hydrazine afforded the 1-e(-) reduction products (Ni6(11+)). As far as we
      are aware, the shortest bond distance of 2.202 A with a partial metal-metal bond
      was observed in Ni6(11+) compounds. The magnetic results of these Ni6(11+)
      compounds are in agreement with a localized model, in which the two terminal
      nickel ions are in a spin state of S = 1 whereas the central Ni3-Ni4 pair in a
      spin state of S = 1/2. The N6(11+) compounds show relatively strong
      antiferromagnetic coupling of about 60 cm(-1) between the terminal and the
      central dinickel ions.

PMID- 16802044
TI  - Metal thiophosphonates and related compounds: an emerging area of supramolecular
      coordination chemistry.
AB  - Nine new compounds containing PS ligands of the types [P(OtBu)S3]2-,
      [ArP(StBu)S2]- and [ArP(OtBu)S2]- are reported (Ar = 4-anisyl). It is
      demonstrated that the topology of alkali metal ion and ligand composition
      influence the structure of supramolecular arrangements.

PMID- 16802045
TI  - [Characteristics of heart failure with preserved ejection fraction: results of
      the Chilean national registry of heart failure, ICARO].
AB  - BACKGROUND: Heart failure (HF) with preserved ejection fraction (EF) is a
      condition of growing interest due to its high prevalence and difficult
      management. AIM: To evaluate the clinical profile of patients hospitalized with
      HF and preserved EF in Chilean hospitals. MATERIAL AND METHODS: Prospective
      registry of 15 centers. Among 649 patients hospitalized in functional class III
      and IV, an echocardiogram was performed to 353. Preserved EF was defined
      quantitatively as an EF >50%. RESULTS: Out the 353 patients, 45% presented an EF
      >50%. Mean age in patients with EF >50 and -50% was 66+/-13 and 67+/-13 years,
      respectively. Among patients with HF and EF >50%, the proportion of women was
      higher (73.7 and 36.3%, p <0.001), the proportion of patients with a history of
      hypertension (76.8 and 65.5%, p <0.05) and the presence of atrial fibrillation
      was also higher (62.3 and 47.8%, p <0.01) and a history of myocardial infarction
      was lower (17.1 and 29.5%, p <0.05). The diastolic diameter of the left ventricle
      was significantly lower in HF with preserved EF (51.0+10 and 63.5+10 mm
      respectively, p <0.001). No differences in the length of hospital stay and
      mortality were observed between HF with depressed and preserved EF. Female gender
      was an independent predictor for the presence of HF with preserved EF (Odds
      ratio: 2.62; confidence intervals: 1.1-6.1). CONCLUSIONS: HF and preserved EF is
      common among hospitalized patients, particularly in women and subjects with a
      history of hypertension and atrial fibrillation. Hospitalization length and
      mortality were similar in patients with either preserved or depressed EF.

PMID- 16802046
TI  - [Social inequities and diabetes among adolescents].
AB  - BACKGROUND: Diseases are not randomly distributed across society. Although the
      results of several studies consistently report higher occurrence of diabetes
      among disadvantaged groups in adult populations, rather sparse and contradictory
      findings have been reported for the young. AIM: To explore whether the
      distribution of self reported diabetes among high school students from the
      Province of Santiago is associated to their socioeconomic position. MATERIAL AND
      METHODS: Data originated from a randomly selected sample of 9,203 Chilean high
      school students. Students answered questionnaires on demographic variables; self
      reported diabetes status; and several dimensions of social position. We used
      logistic regression analyses to study the association between diabetic status and
      the variables 'number of cars owned by the family'; 'paternal income' (in Chilean
      pesos); and 'maternal' and 'paternal achieved education'. RESULTS: Univariate
      analyses suggest the existence of social gradients for the variables number of
      cars owned and parental education. Multivariable [corrected] analyses indicate
      that paternal achieved education is the most influential variable. Students
      coming from families in which the father has only primary school education, are
      significantly more likely to report having diabetes (odds ratio=2.03 confidence
      intervals 1.02-4.04). CONCLUSIONS: In this adolescent population, there is a
      positive association between several indicators of socioeconomic position and
      reported diabetes.

PMID- 16802047
TI  - [Inspiratory muscle function, hemodynamic parameters and dyspnea in patients with
      mitral valve stenosis].
AB  - BACKGROUND: The mechanism involved in dyspnea in patients with mitral valve
      stenosis (MS) is not completely understood. AIM: To evaluate in patients with MS,
      changes in hemodynamic parameters during the assessment of inspiratory muscle
      endurance (IME) and the relationship between IME, hemodynamics and dyspnea.
      SUBJECTS AND METHODS: We studied 13 patients (9 in NYHA class II and 4 in class
      III). Endurance was evaluated using a two minute incremental threshold loading
      test, to obtain the maximal sustainable inspiratory pressure (SIP), and maximal
      inspiratory load (MIL). During the test, cardiac output (CO), mean pulmonary and
      capillary pressures (PAP and PCP, respectively), were evaluated. RESULTS:
      Compared to six normal subjects, MS patients had reduced SIP and MIL (p <0.01),
      which correlated with baseline index of dyspnea (r= 0.57 and r=0.52,
      respectively, p <0.05). At the end of the test period, basal CO, cardiac index
      (CI), PAP and PCP increased from 3.4 to 4.0 l/min-1; 2.1 to 2.5 l/min-1/m-2; 15
      to 25 and 11 to 18 mmHg, respectively (p <0.01). No relationship between IME and
      hemodynamic parameters was found. CONCLUSIONS: IME is reduced and is closely
      related to dyspnea in these patients with MS. The observed low CI, suggests that
      muscle underperfusion could contribute to this dysfunction during the
      inspiratory.

PMID- 16802048
TI  - [Gallbladder cancer: trend and risk distribution in Chile].
AB  - BACKGROUND: Gallbladder cancer (GBC) is the first cause of death by cancer among
      Chilean women and mortality has not improved in the last 20 years. AIM: To study
      GBC mortality trend from 1985-2002, analyze risk differentials by age, sex,
      geographic region and accessibility to surgery. MATERIAL AND METHODS: Mortality
      data was obtained from death certificate databases. Population data was obtained
      from the census and biliary surgery information, from Ministry of Health
      registries. Standardized Mortality rates were based in the world population;
      trend was analyzed with point of change methods. RESULTS: From 1985 to 2002,
      27,183 GBC deaths occurred, 1,510 per year. The absolute number of deaths
      increased in 65% but standardized mortality rates remained unchanged at 11.3 per
      100,000. These were higher among women than men (15.6 and 7.0, respectively, with
      a risk ratio of 2.2). Sex ratio peaked at ages 35-54 with risk ratio of 4.1.
      Death risk increased from North to South, peaking in poorer areas, especially in
      places with rural population and Mapuche ethnic admixture. Mortality appear to
      correlate with the rate of people waiting for gallbladder surgery, but not
      reaching statistical significance (r(2) 0.27, ns). Compared with other countries,
      Chile has a higher rate of GBC deaths in relation to its gross domestic product
      per capita. CONCLUSIONS: There is a high and persistent persistent risk for GBC
      in Chile, particularly among women, from the Southern regions where gallbladder
      surgery is insufficient for the needs, as reflected by the rates of people
      waiting for biliary surgery. GBC rates could be dropped by offering gallbladder
      surgery to everyone waiting for it and to those incident cases with gallstones.

PMID- 16802049
TI  - [Partial or total replacement of the aortic arch. Experience in 23 patients].
AB  - BACKGROUND: Surgery of the aortic arch is a very complex procedure since it
      requires protective strategies for the brain, heart and rest of the body. AIM: To
      communicate our experience in the first 23 total or partial replacements of
      aortic arch. MATERIAL AND METHODS: Retrospective search in the database of the
      Cardiovascular Surgery Unit for patients subjected to partial or total
      replacement of the aortic arch since 1998. RESULTS: Between 1988 and 2002, 23
      patients were operated. Seventeen had aortic dissection (10 acute and 7 chronic),
      five had an atherosclerotic aneurysm and one had a traumatic lesion. Thirteen
      patients were subjected to a replacement of the arch plus ascending aorta, six to
      a replacement of the arch plus descending aorta and four to a replacement of the
      arch, ascending and descending aorta. Seven patients had previous operation of
      the thoracic aorta. Arterial perfusion was done via the femoral artery, axillary
      artery or a combination of both. A hypothermic circulatory arrest was induced in
      22; it was associated with cerebral retro perfusion alone in 8 patients,
      antegrade cerebral perfusion in 5; isolated or associated axillary perfusion was
      used in five patients. In seven, procedures on the aortic or mitral valve, or
      coronary artery operations were added. Operative mortality was 26%, 3 of the 8
      patients operated as an emergency and 3 of 15 elective operations. There was no
      mortality among those without dissection and of 7 chronic dissections, one died.
      All patients were followed for an average of 45 months. Two patients required
      reinterventions on the aorta and one for colon cancer. There was one late death
      of unknown cause. Postoperative complications were agitation, bleeding and
      temporary vocal cord dysfunction. CONCLUSIONS: There is a learning curve, where
      more extensive operations, particularly those done as emergency or for
      dissections, had an increased operative risk.

PMID- 16802050
TI  - [Evolution of mortality and current status of an HIV-infected population cared
      for at a comprehensive HIV/AIDS center in Chile].
AB  - BACKGROUND: Chile, a middle-income country with an HIV epidemic of moderate
      proportions (global infection rate 0.2%) began a government sponsored, free,
      highly active antiretroviral therapy (HAART) for patients from the public health
      system in 2001 reaching in 2004 a 100% coverage. Arriaran Foundation (AF) is the
      largest public AIDS care center for adults in the country. AIM: To show the
      present status of the AF population and the evolution of mortality. MATERIAL AND
      METHODS: Review of AF database from 1991-2004 that at 12/31/2004 had a total
      cumulative population of 2,259 adult patients; an active census of 1,065 patients
      and admitting rate 160-190 patients per years. RESULTS: The global mortality
      registered was 33.4%, with decreasing annual mortality from 15.7% of its active
      population in 1995 to 1.9% in 2004. As of 12/31/2004, 817 patients (76.7%) were
      receiving antiretroviral therapy (ART); and 19.3% either did not require nor
      accept it. Thirty one percent received Combivir and nevirapine, with undetectable
      viral load (<400 copies per ml) in 78%. Thirty percent received Combivir and
      efavirenz with undetectable viral load in 80% at last count. Both regimens were
      used mainly as first therapy. Lopinavir/ritonavir was received by 6.3% of
      patients, mainly for post failure therapy and 58% had undetectable viral load. A
      baseline CD4 count <200 x mm(3) was present in 70% of patients, 45.3% had a count
      below 100 and 47.8% had clinical AIDS. At the last follow up assessment, CD4
      count was <200 in 36.8%, <100 in 10.6% and 200-350 in 44.9%. CONCLUSION: The
      expanded access program to ART in a public, comprehensive AIDS care center in
      Chile has been highly successful in reaching high undetectability (75%), reducing
      mortality and improving immune status despite very advanced baseline disease.

PMID- 16802051
TI  - [Clinical, functional and hemodynamic features of patients with pulmonary
      arterial hypertension].
AB  - BACKGROUND: Pulmonary Arterial Hypertension is a rare, progressive and
      devastating disease with severe consequences in quality of life and survival.
      AIM: A clinical, functional and hemodynamic assessment of patients with pulmonary
      arterial hypertension and categorization according to severity. MATERIAL AND
      METHODS: Prospective registry of patients with arterial pulmonary hypertension,
      hemodynamically defined. Clinical evaluation was performed using World Health
      Organization functional score (I to IV) and Borg dyspnea scale. Six minute
      walking test, echocardiography and right heart catheterization were used for
      functional and hemodynamic assessment. Intravenous Adenosine was used to assess
      vascular reactivity during the hemodynamic evaluation. RESULTS: Twenty nine
      patients were included (25 women, age range 16-72 years). Pulmonary hypertension
      was idiopathic in 11, associated to connective tissue disease in seven,
      associated to congenital heart disease in nine and associated to chronic
      thromboembolism in two. The mean lapse of symptoms before assessment was 2.9
      years and 100% had dyspnea (Borg 5.1). Functional class I, II, III and IV was
      observed in 0, 5, 21 and 3 patients respectively. Six minutes walking test was
      378+/-113 m. Mean pulmonary pressure was 59.4+/-12.2 mmHg, cardiac index was
      2.57+/-0.88 and pulmonary vascular resistance index: 1798.4+/-855 (dyne.sec)/cm5.
      Nine patients had a mean pulmonary arterial pressure >55 mmHg and a cardiac index
      <2.1, considered as bad prognosis criteria. Adenosine test was positive in 17%.
      CONCLUSIONS: This group of patients with Pulmonary Arterial Hypertension was
      mainly conformed by young females, with a moderate to severe disease.

PMID- 16802053
TI  - [Expectancy of vacation as a determining factor of the annual rhythm of
      menarche].
AB  - BACKGROUND: Our previous studies have shown that the monthly rhythm of menarche
      is associated to the expectancy of holidays or vacations. If this hypothesis is
      true, menarche episodes in Chile should cluster in December, the month prior to
      summer vacations. AIM: To study whether the expectancy of holidays or vacations
      is the main determinant of the annual rhythm of menarche. MATERIAL AND METHODS:
      During 1990 and 1991, a questionnaire about the date of birth and date of
      menarche, was applied to girls living in Santiago (Chile) and Medellin
      (Colombia), aged 8 to 18.5 years. They were requested to register the year, month
      or day of menarche, only if they recalled it precisely. RESULTS: Discarding
      clerical errors, data was obtained from 3,225 Chilean and 3,435 Colombian girls.
      Of these 73 and 63% of Chilean and Colombian girls recalled the day of menarche.
      Among Chilean girls an excess of menarche episodes was observed in December,
      January and February. The mean age per month of menarche reached its highest
      value of 155.6+/-15 months in December and fell to 148+/-17 months in January (p
      <0.001). Among Colombian girls, mean age per month of menarche was also higher in
      December and lower in January (152+/-15 and 147+/-14 months respectively, p
      <0.001). However a peak of 152+/-15 months was also observed in June.
      CONCLUSIONS: A similar distribution of menarche episodes was observed among
      Chilean and Colombian girls, with a peak in the months preceding holidays. The
      influence of the photoperiod is unlikely since Medellin is located in parallel 6
      and there are little variations in daylight exposure in the different seasons.
      Therefore, our data supports the hypothesis that the prospect of holidays is a
      determinant of menarche.

PMID- 16802052
TI  - [Etiology and prognostics factors of community-acquired pneumonia among adults
      patients admitted to a regional hospital in Chile].
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious illness in
      Chile. AIM: To evaluate the etiology, severity, prognostic factors and blood
      culture yield of CAP requiring hospitalization in Puerto Montt in Southern,
      Chile. PATIENTS AND METHODS: All non immunocompromised adults with CAP admitted
      at Puerto Montt Hospital during one year, were prospectively studied. Clinical
      and radiological assessment was done in all patients. Blood and sputum cultures
      were obtained and serology for atypical agents was determined. RESULTS: We
      studied 200 patients, aged 63+/-19 years (109 males). The prognostic factors
      associated with mortality were an age over 65 years, an altered mental status,
      shock and acute renal failure. Etiology was demonstrated in 29% of patients. The
      most frequent pathogens were Streptococcus pneumoniae (40.7%), Haemophilus
      influenzae (23.7%) and Chlamydia pneumoniae (16.9%). Mixed infections were found
      in 17%. Fifteen atypical pathogens were identified in 12 patients. Of these only
      two received a specific treatment but no one died and their length hospital stay
      was similar than in the rest of the patients. Overall, blood cultures were
      positive in 12.5% of patients, but among alcoholics, 58% were positive. In only
      one percent of cases, positive cultures motivated therapeutic changes among
      clinicians. Eight percent of S pneumoniae strains were penicillin resistant.
      CONCLUSIONS: Atypical agents were a common cause of CAP in this group of
      patients, but their pathogenic role and treatment requirements are debatable.
      Focusing blood cultures on specific groups could improve their yield. The rate of
      Penicillin resistance for S pneumoniae was.

PMID- 16802054
TI  - [Prospective evaluation of the safety and tolerance of colonoscopy in children].
AB  - BACKGROUND: Colonoscopy is a well established diagnostic and therapeutic
      procedure in pediatrics. AIM: To evaluate colon preparation alternatives for
      colonoscopy or sigmoidoscopy, type of sedation, clinical indications and
      findings. PATIENTS AND METHODS: Prospective study of 123 children referred for
      colonoscopy. Demographic data, type of colon preparation, sedation, type of
      endoscope and endoscopic results were obtained. The following day, a phone
      interview was carried out inquiring about duration, quality and adverse effects
      of the sedation and procedure. RESULTS: Seventy one boys (58%) and 52 girls (42%)
      with a mean age of 6.7+/-4.4 years, were recruited. The main indication was lower
      gastrointestinal bleeding (71%). The different colon preparations produced
      elimination of clear liquid stools in 50%, non transparent liquid in 23%, semi
      liquid in 22% and solid in 6% of the patients. Most common side effects were
      abdominal distension (20%) and nausea (16.8%). The most commonly used drugs were
      midazolam (76%) and demerol (43%). The average duration of the procedure was 18.3
      minutes (range: 4-50). The most common findings were rectal polyps (18.7%) and
      hemorrhagic colitis (14.6%). In 77% of cases, the sedation was considered very
      good or good. Colon visualization was described as very good (51%) or good (36%).
      Seventy three percent of children had complete amnesia. The most common adverse
      effect was vomiting (7.5%). CONCLUSION: Lower endoscopies are feasible procedures
      to carry out in children, in an ambulatory basis, with intravenous sedation and
      minimum adverse effects.

PMID- 16802055
TI  - [High prevalence of thyroid dysfunction among psychiatric inpatients].
AB  - BACKGROUND: Thyroid dysfunction is frecuent in psychiatric outpatients and in the
      general Chilean population but there is no information about the prevalence of
      thyroid diseases in Chilean psychiatric inpatients. AIM: To retrospectively
      assess the frequency of thyroidal diseases in psychiatric inpatients. MATERIAL
      AND METHODS: Clinical charts and thyroid assessment of 241 psychiatric inpatients
      (147 women, mean age 33+/-16 years) attended in a University Psychiatric Clinic,
      were reviewed. Psychiatric diagnosis at discharge was made according to DSM IV
      criteria and endocrine diagnosis was made based on international criteria.
      RESULTS: Forty nine patients (20.7%) had thyroid abnormalities. Forty four
      patients had hypothyroidism (18.3%) and five had hyperthyroidism (2.35%). No
      specific associations were found between gender or psychiatric diagnosis and
      endocrine abnormalities. CONCLUSIONS: In this sample, the prevalence of thyroid
      abnormalities was similar to other reports in psychiatric inpatiens and higher
      than in the general population in Chile.

PMID- 16802056
TI  - [Multisite right ventricular stimulation for cardiac failure refractory to
      biventricular resynchronization therapy. Case report].
AB  - The prevalence of congestive heart failure has increased in the world. Despite
      advances in pharmacological treatment, some patients have progression of the
      disease and deterioration of their functional class. In this group of patients
      cardiac resynchronization therapy has been accepted as a treatment option.
      However, some patients are non-responders to cardiac resynchronization, and
      others who respond favorably, will experience reappearance of their symptoms. For
      these patients, multisite stimulation with the implant of a second electrode in
      the right ventricle has been published as a new option. We report a 76 year-old
      woman with a dilated cardiomyopathy, who was treated with resynchronization
      therapy with good clinical response during two years, but symptoms of congestive
      heart failure reappeared and her functional class deteriorated to NYHA class IV.
      She was successfully treated with right ventricular multisite stimulation, with a
      reduction of symptoms that has lasted during the two months of follow up after
      the procedure.

PMID- 16802057
TI  - [Recurrent left atrial myxoma. Report of a case in a 2 year-old boy].
AB  - Primary cardiac tumors are uncommon in pediatric patients. We report a two year
      old boy, who presented a recurrent left atrial myxoma. He was referred for
      cardiologic evaluation because of cardiomegaly on a chest X-ray. An
      echocardiography showed a big left atrial tumor attached to the atrial septum.
      The tumor was uneventfully removed and the pathological examination confirmed a
      myxoma. He remained asymptomatic and during a follow up echocardiography two
      years later, a recurrent tumor was noted. He was successfully operated again,
      remaining free of a new recurrence after 3 years of follow up.

PMID- 16802058
TI  - [Intensive cholesterol lowering therapy to reduce cardiovascular risk].
AB  - Primary and secondary prevention trials have clearly demonstrated that lowering
      serum cholesterol levels with statins reduces the incidence of cardiovascular
      events. Recent studies plus post hoc analysis of previous clinical trials show
      that risk reduction is proportional to the magnitude of LDL cholesterol lowering.
      Therefore, new recommendations of the National Cholesterol Education Program
      (USA) have defined a category of patients with very high cardiovascular risk, who
      should achieve serum LDL cholesterol levels below 70 mg/dl. This proposal will
      require new and more efficient pharmacologic strategies to attain the
      increasingly strict therapeutic goals for LDL cholesterol. This article reviews
      the clinical studies that support the use of intensive lipid lowering therapy to
      reduce cardiovascular risk. An effective reduction of serum cholesterol can be
      obtained using statins in high doses or a combination of hypolipidemic drugs with
      different mechanisms of action.

PMID- 16802059
TI  - [Oxidative stress in critically ill patients].
AB  - Among critically ill patients, several physio-pathological processes such as
      global and local hypo-perfusion, hypoxia, endothelial injury and acidosis have
      been associated with the production and release of large amounts of reactive
      oxygen species (ROS) in a non regulated fashion. Although in physiologic
      conditions ROS influence intracellular processes and participate in the defense
      against infectious organism, in critically ill conditions they are associated
      with potential oxidative damage over cellular structures and with persistent
      activation of the inflammatory response. Mechanisms associated with oxidative
      damage are activation of the macrophage-monocyte system and neutrophils, ischemia
      reperfusion events and intracellular ROS production. Endogenous compounds, mainly
      enzymes, and dietary components act as antioxidant. Several studies show that in
      critically ill patients increase levels of ROS or reduction of antioxidant levels
      are related to disease severity. In animal models of critical diseases,
      antioxidant therapy has shown to reduce mortality. Nevertheless, there are few
      studies in humans that only show improvements in hemodynamic variables, reduction
      in inflammatory mediators levels, decreases in oxidized compounds and that
      suggest a lower incidence of multiple organ failure.

PMID- 16802060
TI  - [Dimensions of medical professionalism. Perspectives for the 21st. Century].
AB  - Medicine is progressively loosing its prestige and efficacy and needs to rebuild
      the moral values that maintain the tacit social contract subscribed between
      doctors and patients. This altruistic commitment to serve people has been
      devaluated by changes in health systems, by advances in knowledge and by social
      and economical changes. The perspective with which humanity faces its future,
      harmed by radical environmental transformations also has contributed to this
      devaluation. Notwithstanding, requirements to provide high quality health care
      and demands to reinstall those fundamental attributes of professional work,
      commit us to introduce or increase the selective learning of those competences to
      health professionals. This new, or renewed form of improving the teaching of
      health sciences, seems to be the unique way to stop the reduction on health care
      professional effectiveness, to maintain quality of care and to accomplish the
      goal of medical profession to serve and take care of humankind health.

PMID- 16802061
TI  - [Grapefruit juice interaction with drugs].

PMID- 16802063
TI  - Ecotoxicological modeling and risk assessment using chemometric tools.

PMID- 16802062
TI  - Megavariate analysis of environmental QSAR data. Part II--investigating very
      complex problem formulations using hierarchical, non-linear and batch-wise
      extensions of PCA and PLS.
AB  - Three extensions of the basic PCA and PLS methodologies are described. These
      extensions are hierarchical, non-linear and batch-based in nature. The objectives
      of these methods are to assist in problem understanding and problem solving in
      very complex (QSAR) problem formulations. The method extensions are illustrated
      using two example QSAR data sets containing many X- and Y-variables.

PMID- 16802064
TI  - A novel RBF neural network training methodology to predict toxicity to Vibrio
      fischeri.
AB  - This work introduces a neural network methodology for developing QSTR predictors
      of toxicity to Vibrio fischeri. The method adopts the Radial Basis Function (RBF)
      architecture and the fuzzy means training strategy, which is fast and repetitive,
      in contrast to most traditional training techniques. The data set that was
      utilized consisted of 39 organic compounds and their corresponding toxicity
      values to Vibrio fischeri, while lipophilicity, equalized electronegativity and
      one topological index were used to provide input information to the models. The
      performance and predictive ability of the RBF model were illustrated through
      external validation and various statistical tests. The proposed methodology can
      be used to successfully model toxicity to Vibrio fischeri for a heterogeneous set
      of compounds.

PMID- 16802065
TI  - Prediction of genotoxicity of various environmental pollutants by artificial
      neural network simulation.
AB  - In order to evaluate human carcinogenic risks, genotoxicity data such as animal
      cancer bioassay are often not available. In this study, to assess the relevance
      of indicator of carcinogenic risks, we used the "molecular diversity approach" to
      estimate the genotoxicity based upon Salmonella genotoxicity test using the umu
      test and systemic toxicity data of the 82 environmental chemicals predicted by
      neural network simulation. The 82 environmental chemicals were randomly selected
      for this study according to the production and usage in Japan. Even in this
      challenging trial for QSTR (Quantitative Structure Toxicity Relationship) study,
      approaches using artificial neural networks can account for about 94% of the
      variation in the genotoxicity results derived by the umu-test.

PMID- 16802066
TI  - Laparoscopic en bloc resection of the right colon and VI hepatic segment for
      locally advanced colon cancer.

PMID- 16802067
TI  - Intensity-modulated radiotherapy with a belly board for rectal cancer.
AB  - BACKGROUND AND AIM: Intensity-modulated radiotherapy (IMRT) techniques can reduce
      the irradiated small bowel volume in rectal cancer patients, but combined use of
      IMRT and a belly board is yet to be reported on for rectal cancer patients. The
      aim of this study was to determine whether additional use of a belly board
      reduced the irradiated small bowel volume observed using IMRT alone in rectal
      cancer patients. MATERIALS AND METHODS: Twenty patients scheduled to receive
      preoperative radiotherapy for rectal cancer underwent two series of CT scans,
      with and without a belly board. IMRT planning was performed using 6-MV photon
      beams and seven equispaced fields. The bladder, small bowel, and planning target
      volume (PTV) were analyzed for doses between 10% and 100% of the prescribed dose
      at 10% intervals. Data were analyzed using Wilcoxon signed rank tests. RESULTS:
      There were no significant differences between patients undergoing IMRT with a
      belly board and those without a belly board in terms of total small bowel
      volumes, bladder, and PTV (p=0.571, p=0.841, and p=0.870, respectively).
      Statistical analysis showed that the irradiated small bowel volume with a belly
      board was smaller than that without a belly board (p<0.05 at 20-100% dose
      levels), with the mean relative reduction in the irradiated small bowel volume
      being 37.8+/-32.8%. CONCLUSION: IMRT with a belly board is more effective than
      IMRT alone in reducing the irradiated small bowel volume. These findings suggest
      that the use of a belly board with IMRT may reduce small bowel complications in
      preoperative radiotherapy.

PMID- 16802068
TI  - [Bamboo nodes as the cause of dysphonias in autoimmune diseases].
AB  - BACKGROUND: In rare cases, dysphonia can be caused by vocal fold deposits called
      "bamboo nodes." They often feature a transverse yellowish appearance of the
      middle third of the vocal cord, resembling a bamboo node. Typical histologic
      signs are similar to rheumatoid nodules. CASE REPORT: We report on a 43-year-old
      woman with known Sharp syndrome and dysphonia. Laryngoscopy showed transverse
      deposits on both vocal folds. The diagnosis of bamboo nodes was made and
      treatment initiated. DISCUSSION/CONCLUSION: Laryngeal deposits should be
      suspected and a thorough laryngostroboscopic examination carried out whenever a
      patient with an autoimmune disease presents with a rough and unstable voice.
      Because the patients may have hoarseness as their primary symptom, it is
      important for otolaryngologists to be familiar with this disorder. Further
      autoimmune investigation should be established. A combination of local laryngeal
      therapy with steroids and subsequent surgery seems to be a useful treatment
      approach for bamboo nodes. To our knowledge this is the first description of a
      patient with Sharp syndrome and bamboo nodes.

PMID- 16802069
TI  - Structure and interaction potentials in solid-supported lipid membranes studied
      by X-ray reflectivity at varied osmotic pressure.
AB  - Highly oriented solid-supported lipid membranes in stacks of controlled number N
      approximately 16 (oligo-membranes) have been prepared by spin-coating using the
      uncharged lipid model system 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC).
      The samples have been immersed in aqueous polymer solutions for control of
      osmotic pressure and have been studied by X-ray reflectivity. The bilayer
      structure and fluctuations have been determined by modelling the data over the
      full q-range. Thermal fluctuations are described using the continuous smectic
      Hamiltonian with the appropriate boundary conditions at the substrate and at the
      free surface of the stack. The resulting fluctuation amplitudes and the pressure
      distance relation are discussed in view of the inter-bilayer potential.

PMID- 16802070
TI  - Chronic cobalt treatment decreases hyperglycemia in streptozotocin-diabetic rats.
AB  - Diabetes is a metabolic disorder characterized by elevated blood glucose levels.
      Although conventional treatments such as insulin and other drugs reduce blood
      glucose, there is still a therapeutic need for effective orally administered
      drugs. Trace elements like vanadium and tungstate have been successfully
      demonstrated to reduce blood glucose in experimental diabetes with minimal
      chronic complications. We investigated the anti-hyperglycemic effects of cobalt
      in streptozotocin-diabetic rats. Normal and diabetic rats were provided with
      drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM
      for four weeks. Body weights and fluid consumption were monitored on a daily
      basis, while food intake was recorded twice every week. Prior to termination, an
      oral glucose tolerance test was performed on the animals. Diabetic rats lost
      significant body weight (357 +/- 2 gm) compared to controls (482 +/- 3 gm). Body
      weight was further reduced by cobalt treatment (290 +/- 2 gm). Although it was
      difficult to establish a dosing regimen without weight loss, food and fluid
      consumption in cobalt-treated diabetic rats improved significantly compared to
      untreated diabetics. Plasma glucose levels were significantly reduced with
      reference to diabetic controls (29.3 +/- 0.9 mM) by the fourth week to a lower
      but still hyperglycemic level (13.6 +/- 3.4 mM). Cobalt-treated diabetic rats
      demonstrated an enhanced ability to clear a glucose load compared to untreated
      diabetics. Cobalt treatment neither affected the feeding and drinking patterns
      nor plasma glucose in normoglycemic animals although body weights decreased
      compared to untreated controls. We conclude that chronic cobalt treatment
      decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to
      glucose.

PMID- 16802071
TI  - Effects of acute and chronic cadmium administration on the vascular reactivity of
      rat aorta.
AB  - The effect of acute and chronic cadmium (Cd) administration on the vascular
      function of the rat aorta was studied. The rats were randomly divided into four
      main groups (A: saline controls under chronic administration, B: Cd-treated rats
      under chronic administration, C: saline controls under acute administration, D:
      Cd-treated rats under acute administration). After their sacrifice, the aortic
      rings were divided into rings with endothelium (E+) and without (E-), and
      suspended in an isolated organ bath with Krebs - Henseleit buffer. Maximal
      tension (T max, in g) was measured in response to potassium chloride (KCl) and
      phenylephrine (PE) in all aortic rings. Relaxation response to acetylcholine
      (ACh) administration was expressed as percent of maximal tension induced by PE.
      Chronic administration: A statistically significant increase of the contraction
      was observed between groups B (i.m. Cd 0.5 mg/kg for 120 days) and A (i.m. 0.9%
      NaCl for 120 days) in response to KCl (20-60 mM) and the T max as well (in both
      the E+ and the E- subgroups). No statistically significant difference was
      observed in response to PE and ACh exposure. Acute administration: A
      statistically significant increase was observed between group D(E+) (i.m. Cd 2
      mg/kg, 8 h before sacrifice) and group C(E+) (i.m. 0.9% NaCl, 8 h before
      sacrifice) in response to 10-30 mM of KCl, and a significant decrease between D(E
      ) and C(E-) in response to 10(-7)-10(-6) M of PE, though T (max) was increased
      between D(E-) and C(E-) with PE exposure. The contractile response levels of the
      E+ aortic rings to PE and ACh showed no statistically significant difference.

PMID- 16802073
TI  - Parent-child development center follow-up project: child behavior problem
      results.
AB  - The long-term effectiveness of the Parent-Child Development Centers (PCDCs) as
      programs to prevent behavior problems in children was examined with follow-up
      data collected 6-13 years after program completion. Data were collected for 581
      children who had been in the programs with their mothers (Ns: Birmingham, 151;
      New Orleans, 186; Houston, 244). Mothers and teachers were interviewed. There
      were few significant differences between program and control groups. Only the
      early cohorts of the Houston program showed significant differences between
      groups on the Child Behavior Checklist (CBCL). EDITORS' STRATEGIC IMPLICATIONS:
      This is a rare example of long-term longitudinal evaluation of a cross-site
      prevention program with a large sample size. Practitioners and program designers
      will be interested in the author's descriptions of cohort and site implementation
      differences. The absence of major effects at follow-up (despite significant short
      term effects) in this well-designed study must caution us against thinking of
      early prevention programs as inoculations.

PMID- 16802072
TI  - Retaining ethnic minority parents in a preventive intervention: the quality of
      group process.
AB  - This study examined relations between group process variables and retention of
      ethnic minority (African American and Hispanic) caregivers in a family-focused
      preventive intervention. Data from the Familias Unidas/SEPI project (Coatsworth,
      Pantin, & Szapocznik, 2002), a randomized, controlled intervention trial, were
      used to cluster participants according to their patterns of retention over 30
      intervention sessions. These person-centered analyses identified three broad
      patterns: (a) dropouts; (b) variable-attenders; and (c) consistent-high
      attenders. Two subgroups of the variable-attender group were also identified: (a)
      intermittent-attenders, and (b) continual-attenders. Discriminant Function
      Analysis (DFA) with follow-up Analysis of Variance tested for differences among
      the three main retention groups on facilitator ratings of participants' general
      level of participation, leadership, positive alliance with the group, and
      negative alliance with the group during the first half of the intervention.
      Leadership and positive alliance significantly discriminated the broad retention
      patterns. Mean level of participation was not significantly different across
      retention groups. Results of DFA and ANOVA analyses using leadership, alliance,
      and participation variables from the first and second halves of the intervention
      indicated only leadership and positive alliance during the second half of the
      intervention discriminated continual-attenders from intermittent-attenders.
      EDITORS' STRATEGIC IMPLICATIONS: The authors describe a promising approach to
      studying facilitators' assessments of client involvement in a family-focused
      preventive intervention. The quality of the participants' behavior during
      sessions, rather than their absolute levels of participation, predicted their
      pattern of retention in the program. Future comparisons of facilitator and parent
      views may prove helpful.

PMID- 16802075
TI  - Right cervical aortic arch and pseudocoarctation of the aorta associated with
      aneurysms and steal phenomena: US, CTA, and MRA findings.
AB  - A 55-year-old woman presented with right cervical aortic arch with
      pseudocoarctation of the aorta further complicated by the presence of multiple
      aneurysms and a high-grade stenosis at the origin of the left subclavian trunk
      from the aorta causing a discrepancy in blood pressure between the right and left
      arms. The branching pattern and the resulting complex steal syndromes involving
      the left carotid and the subclavian system are unique. The computed tomography
      angiography, magnetic resonance angiography, and Doppler ultrasound findings are
      described.

PMID- 16802074
TI  - The effects of two different incentives on recruitment rates of families into a
      prevention program.
AB  - This study experimentally manipulated two incentives for participation (monetary:
      paid participation for sessions and setting: group vs. individual) in a child
      behavior problem prevention program to analyze their effects on recruitment and
      retention of families. A population of 690 eligible families from 15 preschools
      located in socially disadvantaged neighborhoods was invited to participate in a
      parent training (PT) program. The study recruited parents by using advertisements
      that had information describing only the indicated condition (i.e., PT in group
      unpaid, or PT individual-unpaid, or PT in group-paid, or PT individual-paid).
      Results demonstrate significant impact of payment on recruitment and initial
      attendance. Training setting alone (individual or group) did not significantly
      influence these rates. Editors' Strategic Implications: A compelling case is made
      for the utility of monetary incentives to increase proportions of low-income
      families in prevention research and programs. Evaluators and program designers
      should note the impressive use of the experimental design and hierarchical linear
      modeling to test the effects on recruitment.

PMID- 16802076
TI  - Retrograde rotablator in limb salvage: a new technique using an open approach.
AB  - Conventional vascular surgery and balloon angioplasty have poor results in severe
      and diffuse atherosclerotic disease of the infrapopliteal arteries. High-speed
      rotational atherectomy (Auth Rotablator) has not succeeded either, because of
      poor long-term patency and the non-reflow phenomenon. We report a case of limb
      salvage with long occlusion of the three infrapopliteal vessels. The anterior
      tibial artery was treated with retrograde Auth Rotablator atherectomy by an open
      approach through the pedal artery, resulting in full patency of the anterior
      tibial artery and healing of the skin lesions. The microparticulate debris from
      the ablation was drained out through the pedal arteriotomy, avoiding the
      complications associated with conventional antegrade high-speed rotational
      atherectomy.

PMID- 16802077
TI  - Radiation exposure to patient and staff in hepatic chemoembolization: risk
      estimation of cancer and deterministic effects.
AB  - The purpose of the study was to determine the risks of radiation-induced cancer
      and deterministic effects for the patient and staff in transarterial
      chemoembolization (TACE) of hepatocellular carcinoma (HCC). Sixty-five patients
      with HCC underwent the first cycle of TACE. Thermoluminescence dosemeters and
      conversion factors were used to measure surface doses and to calculate organ
      doses and effective dose. For the patient, the risk of fatal cancer and severe
      genetic defect was in the magnitude of 10(-4) and 10(-5), respectively. Five
      patients showed surface doses over the first lumbar vertebra exceeding 2000 mSv
      and 45 patients showed doses over the spine or the liver region above 500 mSv.
      The risk of fatal cancer and severe genetic defect for the radiologist and
      assistant was in the magnitude of 10(-7) to 10(-8). They could exceed the
      threshold for lens opacity in the case of more than 490 and 1613 TACE yearly for
      a period of many years, respectively. Radiation dose could lead to local
      transient erythema and/or local depression of hematopoiesis in many patients
      after TACE. For the radiologist and assistant, risk of fatal cancer and genetic
      defect and lens opacity might arise when they perform interventions such as TACE
      intensively.

PMID- 16802078
TI  - Lower limb arteriovenous communications in diabetes mellitus: a potential reason
      for aggravation of ischemic symptoms.
AB  - The aim of this study was to assess the prevalence and to evaluate the clinical
      associations of arteriovenous communications in patients with diabetes mellitus
      (DM) and lower limb peripheral arterial ischemia. Peripheral arteriography of DM
      patients from an eight-year period (1993-2000) was evaluated retrospectively by
      two observers. The presence of arteriovenous communications, defined as occurring
      without evidence of a preceding precipitating event, and the distribution and
      severity of the vascular disease were evaluated. The type (non-insulin-dependent
      DM or insulin-dependent DM) and the duration of the DM, the presenting symptoms,
      and the presence of a peripheral neuropathy were documented by a review of the
      clinical records. A total of 348 arteriography studies in 285 DM patients were
      evaluated (duration of DM: median, 16 years; range, 7-42 years); an arteriovenous
      communication was present in 14/285 patients (4.9%), 9 male and 5 female (median
      age, 71 years; range, 17-84 years). Symptoms were those of a peripheral leg ulcer
      (n = 11), claudication (n = 3), and gangrene (n = 1), with symptoms ipsilateral
      to the side of the arteriovenous communication in 13/14 patients. The sites of
      the arteriovenous communications were infra popliteal (n = 7), popliteal (n = 3),
      superficial femoral artery (n = 3), and common femoral artery (n = 1). Features
      of a peripheral neuropathy were found in 12/14 and ipsilateral to the side of the
      communication in 11/12. Arteriovenous communications in the peripheral femoral
      arterial system of patients with DM is an uncommon finding. Although not proven
      in the current study, arteriovenous communications might be associated with more
      severe symptoms than that attributable to the underlying vascular disease alone.

PMID- 16802079
TI  - Thermal protection with 5% dextrose solution blanket during radiofrequency
      ablation.
AB  - A serious complication for any thermal radiofrequency ablation is thermal injury
      to adjacent structures, particularly the bowel, which can result in additional
      major surgery or death. Several methods using air, gas, fluid, or thermometry to
      protect adjacent structures from thermal injury have been reported. In the cases
      presented in this report, 5% dextrose water (D5W) was instilled to prevent injury
      to the bowel and diaphragm during radiofrequency ablation. Creating an Insulating
      envelope or moving organs with D5W might reduce risk for complications such as
      bowel perforation.

PMID- 16802080
TI  - Performance of laparoscopy in identifying malignant ovarian cysts.
AB  - BACKGROUND: Peroperative identification of malignancy is crucial to management
      planning for ovarian cysts. The aim of this study was to evaluate the performance
      of laparoscopy in identifying malignant ovarian cysts. METHODS: Patients
      undergoing laparoscopy for ovarian cysts from 1998 to 2001 were enrolled
      prospectively. Physical findings, Doppler ultrasonography, and serum CA 125
      served to compute two risk-of-malignancy indexes (RMI-1 and RMI-2), and
      laparoscopy findings served to categorize lesions as benign, possibly malignant,
      or malignant. Frozen sections were examined as needed. Final histology was the
      reference. RESULTS: Of 313 patients, 294 had benign cysts, six borderline
      lesions, and 13 malignancies. Sensitivity and specificity were respectively 84
      and 93% for RMI-1, 92 and 80% for RMI-2, 100 and 99% for laparoscopy, 91 and 100%
      for frozen sections, and 100 and 100% for laparoscopy plus frozen sections, which
      had 100% negative predictive value. Six (1.8%) adverse events occurred.
      CONCLUSIONS: Laparoscopy reliably identifies ovarian cancer and borderline
      disease. Morbidity is low compared to oncologic surgery.

PMID- 16802081
TI  - 2D autocorrelation modelling of the inhibitory activity of cytokinin-derived
      cyclin-dependent kinase inhibitors.
AB  - The inhibitory activity towards p34(cdc2)/cyclin b kinase (CBK) enzyme of 30
      cytokinin-derived compounds has been successfully modelled using 2D spatial
      autocorrelation vectors. Predictive linear and non-linear models were obtained by
      forward stepwise multi-linear regression analysis (MRA) and artificial neural
      network (ANN) approaches respectively. A variable selection routine that selected
      relevant non-linear information from the data set was employed prior to networks
      training. The best ANN with three input variables was able to explain about 87%
      data variance in comparison with 80% by the linear equation using the same number
      of descriptors. Similarly, the neural network had higher predictive power. The
      MRA model showed a linear dependence between the inhibitory activities and the
      spatial distributions of masses, electronegativities and van der Waals volumes on
      the inhibitors molecules. Meanwhile, ANN model evidenced the occurrence of non
      linear relationships between the inhibitory activity and the mass distribution at
      different topological distance on the cytokinin-derived compounds. Furthermore,
      inhibitors were well distributed regarding its activity levels in a Kohonen self
      organizing map (SOM) built using the input variables of the best neural network.

PMID- 16802082
TI  - Cellular modelling of secondary radial growth in conifer trees: application to
      Pinus radiata (D. Don).
AB  - The radial growth of conifer trees proceeds from the dynamics of a merismatic
      tissue called vascular cambium or cambium. Cambium is a thin layer of active
      proliferating cells. The purpose of this paper was to model the main
      characteristics of cambial activity and its consecutive radial growth. Cell
      growth is under the control of the auxin hormone indole-3-acetic. The model is
      composed of a discrete part, which accounts for cellular proliferation, and a
      continuous part involving the transport of auxin. Cambium is modeled in a two
      dimensional cross-section by a cellular automaton that describes the set of all
      its constitutive cells. Proliferation is defined as growth and division of
      cambial cells under neighbouring constraints, which can eliminate some cells from
      the cambium. The cell-growth rate is determined from auxin concentration,
      calculated with the continuous model. We studied the integration of each
      elementary cambial cell activity into the global coherent movement of macroscopic
      morphogenesis. Cases of normal and abnormal growth of Pinus radiata (D. Don) are
      modelled. Abnormal growth includes deformed trees where gravity influences auxin
      transport, producing heterogeneous radial growth. Cross-sectional microscopic
      views are also provided to validate the model's hypothesis and results.

PMID- 16802083
TI  - Information capacity of nucleotide sequences and its applications.
AB  - The information capacity of nucleotide sequences is defined through the specific
      entropy of frequency dictionary of a sequence determined with respect to another
      one containing the most probable continuations of shorter strings. This measure
      distinguishes a sequence both from a random one, and from ordered entity. A
      comparison of sequences based on their information capacity is studied. An order
      within the genetic entities is found at the length scale ranged from 3 to 8. Some
      other applications of the developed methodology to genetics, bioinformatics, and
      molecular biology are discussed.

PMID- 16802084
TI  - Markov model of haploid random mating with given distribution of population size.
AB  - An exact Markov chain model is formulated and computed for random mating in a
      haploid gamete pool. There are two versions of the gamete, and there is a finite
      number of diploid monoecious organisms. The founder population is given, and the
      subsequent generations allow a prescribed statistical distribution over different
      population sizes. The non-homogeneous Markov chain works on the haploid gamete
      level provided the probability of self-fertilization is 1/n, where n is the
      number of diploid individuals. Standard deviations of gamete frequencies and
      fixation probabilities are calculated. Effective population sizes for different
      population size distributions are estimated, including periodic bottlenecks.

PMID- 16802085
TI  - Conflicting immune responses can prolong the length of infection in Plasmodium
      falciparum malaria.
AB  - We have recently proposed a new model for antigenic variation in Plasmodium
      falciparum that relies on a network of partially cross-protective immune
      responses to orchestrate this complex immune evasion process. In addition to
      exhibiting prolonged oscillations of single variants that resemble the sequential
      dominance of immunologically distinct antigenic types, the model implies that a
      higher efficacy of cross-reactive immunity actually increases the length of
      infection while reducing severity of disease. Here, we analyse the behaviour of a
      reduced system under conditions of perfect synchrony between variants to
      demonstrate that these features of this system can be attributed to the
      antagonism between cross-reactive and variant-specific responses.

PMID- 16802086
TI  - Two continuum models for the spreading of myxobacteria swarms.
AB  - We analyze the phenomenon of spreading of a Myxococcus xanthus bacterial colony
      on plates coated with nutrient. The bacteria spread by gliding on the surface. In
      the first few hours, cell growth is irrelevant to colony spread. In this case,
      bacteria spread through peninsular protrusions from the edge of the initial
      colony. We analyze the diffusion through the narrowing reticulum of cells on the
      surface mathematically and derive formulae for the spreading rates. On the time
      scale of tens of hours, effective diffusion of the bacteria, combined with cell
      division and growth, causes a constant linear increase in the colony's radius.
      Mathematical analysis and numerical solution of reaction-diffusion equations
      describing the bacterial and nutrient dynamics demonstrate that, in this regime,
      the spreading rate is proportional to the square root of both the effective
      diffusion coefficient and the nutrient concentration. The model predictions agree
      with the data on spreading rate dependence on the type of gliding motility.

PMID- 16802087
TI  - Modelling the effect of caveolae on G-protein activation.
AB  - In this paper, we study the effects on G-protein activation of a non-uniform
      distribution of signalling components. The spatial heterogeneity is attributed to
      caveolae, a specific membrane microdomain which has been observed to redistribute
      and concentrate signalling molecules. Diffusive coagulation-fragmentation
      equations are used to describe the aggregation of caveolin homo-oligomers and the
      subsequent formation of caveolae. A system of reaction-diffusion equation is thus
      formulated and, in order to describe the restrictions imposed by caveolae on the
      movement of receptors and G-protein, a segregation coefficient is introduced
      which serves to regulate the preference of the species to segregate according to
      the concentration of caveolae. The results demonstrate that the heterogeneous
      distribution of the signalling components and the efficiency of G-protein
      activation can vary significantly, depending on the concentration of caveolae.

PMID- 16802088
TI  - Bayesian modelling of an epidemic of severe acute respiratory syndrome.
AB  - This paper analyses data arising from a SARS epidemic in Shanxi province of China
      involving a total of 354 people infected with SARS-CoV between late February and
      late May 2003. Using Bayesian inference, we have estimated critical
      epidemiological determinants. The estimated mean incubation period was 5.3 days
      (95% CI 4.2-6.8 days), mean time to hospitalisation was 3.5 days (95% CI 2.8-3.6
      days), mean time from symptom onset to recovery was 26 days (95% CI 25-27 days)
      and mean time from symptom onset to death was 21 days (95% CI 16-26 days). The
      reproduction ratio was estimated to be 4.8 (95% CI 2.2-8.8) in the early part of
      the epidemic (February and March 2003) reducing to 0.75 (95% CI 0.65-0.85) in the
      later part of the epidemic (April and May 2003). The infectivity of symptomatic
      SARS cases in hospital and in the community was estimated. Community SARS cases
      caused transmission to others at an estimated rate of 0.4 per infective per day
      during the early part of the epidemic, reducing to 0.2 in the later part of the
      epidemic. For hospitalised patients, the daily infectivity was approximately 0.15
      early in the epidemic, but fell to 0.0006 in the later part of the epidemic.
      Despite the lower daily infectivity level for hospitalised patients, the long
      duration of the hospitalisation led to a greater number of transmissions within
      hospitals compared with the community in the early part of the epidemic, as
      estimated by this study. This study investigated the individual infectivity
      profile during the symptomatic period, with an estimated peak infectivity on the
      ninth symptomatic day.

PMID- 16802089
TI  - Unique reconstruction of tree-like phylogenetic networks from distances between
      leaves.
AB  - In this paper, a class of rooted acyclic directed graphs (called TOM-networks) is
      defined that generalizes rooted trees and allows for models including
      hybridization events. It is argued that the defining properties are biologically
      plausible. Each TOM-network has a distance defined between each pair of vertices.
      For a TOM-network N, suppose that the set X consisting of the leaves and the root
      is known, together with the distances between members of X. It is proved that N
      is uniquely determined from this information and can be reconstructed in
      polynomial time. Thus, given exact distance information on the leaves and root,
      the phylogenetic network can be uniquely recovered, provided that it is a TOM
      network. An outgroup can be used instead of a true root.

PMID- 16802090
TI  - Integrin activation--the importance of a positive feedback.
AB  - Integrins mediate cell adhesion and are essential receptors for the development
      and functioning of multicellular organisms. Integrin activation is known to
      require both ligand and talin binding and to correlate with cluster formation but
      the activation mechanism and precise roles of these processes are not yet
      resolved. Here mathematical modeling, with known experimental parameters, is used
      to show that the binding of a stabilizing factor, such as talin, is alone
      insufficient to enable ligand-dependent integrin activation for all observed
      conditions; an additional positive feedback is required.

PMID- 16802091
TI  - An ESS for the height of a plant population, or an optimal height for an
      individual?--Rethinking game-theoretic models for plant height.
AB  - Plants only interact with neighbors over restricted distances, so local
      conditions are of great significance for plants. It is therefore important to
      consider spatial structure and neighborhood effects if we are to understand
      plants' strategies. We constructed a spatially-explicit, game theory model to
      explore optimal height growth at the individual-level. In the model, there is no
      ESS for height growth at the population level, because there is an
      "instantaneous" optimal height growth strategy for the individual plant that
      changes depending on the local light environment. The optimal strategy is
      plasticity in response to local conditions. Game-theoretic models for plant
      phenotypic traits should move from "mean-field approximations" towards explicit
      modeling of local interactions.

PMID- 16802092
TI  - Cloning and characterization of a novel, human cellular retinaldehyde-binding
      protein CRALBP-like (CRALBPL) gene.
AB  - Cellular retinaldehyde-binding protein (CRALBP) plays a role in the vertebrate
      visual process as a substrate-routing protein. It belongs to a widespread lipid
      binding SEC14-like protein family. All the members of the family have the lipid
      binding domain called CRAL-TRIO. Here we have isolated a new human CRAL-TRIO
      domain containing a CRALBP-like (CRALBPL) gene from the cDNA library of human
      adult brain. The CRALBPL gene consisted of 1,694 bp and had an ORF encoding
      putatively 354 amino acids with a CRAL-TRIO domain from 118 to 279 aa. The
      expression pattern in 18 human tissues indicated that CRALBPL gene was mainly
      expressed in brain. The alignment of CRAL-TRIO domain showed that CRALBPL had 45%
      identity with human CRALBP. Subcellular location revealed that CRALBPL protein
      was located in the cytoplasm of HeLa cells. Western blotting indicated that the
      CRALBPL had a molecular weight of about 40 kDa.

PMID- 16802093
TI  - Direct estimation of the oxygen requirements of Achromobacter xylosoxidans for
      aerobic degradation of monoaromatic hydrocarbons (BTEX) in a bioscrubber.
AB  - The O2 requirements for biomass production and supplying maintenance energy
      demands during the degradation of both benzene and ethylbenzene by Achromobacter
      xylosoxidans Y234 were measured using a newly proposed technique involving a
      bioscrubber. Using this approach, relevant microbial parameter estimates were
      directly and simultaneously obtained via linear regression of pseudo steady-state
      data. For benzene and ethylbenzene, the biomass yield on O2, Y(X/O2), was
      estimated on a cell dry weight (CDW) basis as 1.96 +/- 0.25 mg CDW mgO2(-1) and
      0.98 +/- 0.17 mg CDW mgO2(-1), while the specific rate of O2 consumption for
      maintenance, m(O2), was estimated as 0.041 +/- 0.008 mgO(2) mg CDW(-1) h(-1) and
      0.053 +/- 0.022 mgO(2) mg CDW(-1) h(-1), respectively.

PMID- 16802094
TI  - Monitoring the formation of an Aureobasidium pullulans biofilm in a bead-packed
      reactor via flow-weighted magnetic resonance imaging.
AB  - The biofilm-forming fungus, Aureobasidium pullulans DSM 2404, was grown in a bead
      packed reactor. Alterations within the reactor were analysed in several cross
      sectional slices by magnetic resonance imaging (MRI) with flow contrast. For the
      first time, biofilm accumulation could be continuously elucidated without using
      any contrast agents, and the non-stationary flow through the fixed-bed reactor
      could be visualized. The results indicate that the non-stationary flow through
      the biofilm reactor changes significantly due to the changing reactor morphology.
      Preferential flow lines arise during biofilm formation. The accumulation of the
      biomass was determined and compared to gravimetrical biomass data. The described
      technique can be used to monitor hydrodynamic transport, and to combine flow
      field characteristics with morphological data for the prediction of undesirable
      reactor processes, e.g. clogging.

PMID- 16802095
TI  - Biodegradation of cyanide by a white rot fungus, Trametes versicolor.
AB  - The cyanide degradation abilities of three white rot fungi, Trametes versicolor
      ATCC 200801, Phanerochaete chrysosporium ME 496 and Pleurotus sajor-caju, were
      examined. T. versicolor was the most effective with 0.35 g dry cell/100 ml
      degrading 2 mM KCN (130 mg/l) over 42 h, at 30 degrees C, pH 10.5 with stirring
      at 150 rpm.

PMID- 16802096
TI  - Cloning, expression and characterization of a thiolase gene from Clostridium
      pasteurianum.
AB  - A thl gene encoding the thiolase (EC 2.3.1.9) of Clostridium pasteurianum was
      cloned by thermal asymmetric interlaced (TAIL) PCR. It consists of 1179 bp with
      36.8% GC content and encodes 392 amino acids with a deduced molecular mass of
      40,954 Da and shows 77% identity and 88% similarity to that of Clostridium tetani
      E88 and should be classified as a biosynthetic thiolase with three conserved
      residues Cys89, Cys382 and His352. The gene was over-expressed in Escherichia
      coli and the thiolase was purified with Ni-NTA agarose column to homogeneity. The
      K(m) of this thiolase for acetoacetyl-CoA is 0.13 mM with 0.06 mM CoASH at pH
      8.2, 25 degrees C and a V(max) value of 46 micromol min(-1) mg(-1).

PMID- 16802097
TI  - Functional purification of the monocarboxylate transporter of the yeast Candida
      utilis.
AB  - Plasma membranes of the yeast, Candida utilis, were solubilized with octyl-beta-D
      glucopyranoside and a fraction enriched in the lactate carrier was obtained with
      DEAE-Sepharose anion-exchange chromatography, after elution with 0.4 M NaCl. The
      uptake of lactic acid into proteoliposomes, containing the purified protein
      fraction and cytochrome c oxidase, was dependent on a proton-motive force and the
      transport specificity was consistent with the one of C. utilis intact cells.
      Overall, we have obtained a plasma membrane fraction enriched in the lactate
      carrier of C. utilis in which the transport properties were preserved. Given the
      similarities between the lactate transport of C. utilis and the one of mammalian
      cells, this purified system could be further explored to screen for specific
      lactate inhibitors, with potential therapeutic applications.

PMID- 16802098
TI  - Novel hydrogel obtained by chitosan and dextrin-VA co-polymerization.
AB  - A novel hydrogel was obtained by reticulation of chitosan with dextrin
      enzymatically linked to vinyl acrylate (dextrin-VA), without cross-linking
      agents. The hydrogel had a solid-like behaviour with G' (storage modulus) >> G''
      (loss modulus). Glucose diffusion coefficients of 3.9 x 10(-6) +/- 1.3 x 10(-6)
      cm(2)/s and 2.9 x 10(-6) +/- 0.5 x 10(-6) cm(2)/s were obtained for different
      substitution degrees of the dextrin-VA (20% and 70% respectively). SEM
      observation revealed a porous structure, with pores ranging from 50 microm to 150
      microm.

PMID- 16802099
TI  - Tailoring tropane alkaloid accumulation in transgenic hairy roots of Atropa
      baetica by over-expressing the gene encoding hyoscyamine 6beta-hydroxylase.
AB  - Atropa baetica hairy roots, over-expressing cDNA from Hyoscyamus niger encoding
      the gene for hyoscyamine 6beta-hydroxylase (H6H), were produced by Agrobacterium
      rhizogenes infection. The transgenic roots over-expressing h6h had an altered
      alkaloid profile in which hyoscyamine was entirely converted into scopolamine. In
      the best h6h clone, scopolamine accumulation increased 9-fold compared to plants,
      amounting to 5.6 mg g dry wt(-1), some of which was released into the liquid
      medium. Only negligible amounts of hyoscyamine were detected. In contrast, the
      gus control culture contained a much higher amount of hyoscyamine than
      scopolamine, mimicking the situation in the plant. At the molecular level, a
      higher conversion of hyoscyamine into scopolamine was related to a higher level
      of h6h mRNA; in some instances this was 5 - 10-fold higher.

PMID- 16802100
TI  - Starch-branching enzyme I gene (IbSBEI) from sweet potato (Ipomoea batatas);
      molecular cloning and expression analysis.
AB  - The cDNA of the starch-branching enzyme I gene (IbSBEI) in the sweet potato
      (Ipomoea batatas) has been cloned and sequenced. The IbSBEI amino acid sequence
      was 81% identical to that of potato StSBEI. DNA gel-blot analyses demonstrated
      that at least two copies of IbSBEI are present in the sweet potato genome. IbSBEI
      was strongly expressed in tuberous roots. Transcript levels in the roots of
      single leaf cuttings were extremely low during the first 15-40 d after planting
      and continuously increased up to 50 d, by which time the tuberous roots had
      almost completely developed. This indicates that IbSBEI may work in concert with
      the AGPase large subunit during the primary phase of starch granule formation.

PMID- 16802101
TI  - Whole genome phage display selects for proline-rich Boi polypeptides against
      Bem1p.
AB  - Interaction selection by biopanning from a fragmented yeast proteome displayed on
      filamentous phage particles was successful in identifying proline-rich fragments
      of Boi1p and Boi2p. These proteins bind to the second "src homology region 3''
      (SH3) domain of Bem1p, a protein of Saccharomyces cerevisiae involved in bud
      formation. Target Bem1p was a doubly-tagged recombinant, Bem1([Asn142-Ile551]),
      which strongly interacts in ELISA with a C-terminal 75 amino acids polypeptide
      from Cdc24p exposed on phage. The whole yeast genomic display library contained
      approximately 7.7 x 10(7) independent clones of sheared S. cerevisiae genomic DNA
      fused to a truncated M13 gene III. This study corroborates the value of
      fragmented-proteome display to identify strong and direct interacting protein
      modules.

PMID- 16802102
TI  - Chemical-induced autoexcision of selectable markers in elite tomato plants
      transformed with a gene conferring resistance to lepidopteran insects.
AB  - Marker-free transgenic tomato plants harboring a synthetic Bacillus thuringiensis
      endotoxin gene, cryIAc, were obtained by using a chemically regulated, Cre/loxP
      mediated site-specific DNA recombination system, in which the selectable marker
      neomycin phosphotransferase gene flanked by two directly oriented loxP sites was
      located between the cauliflower mosaic virus 35S promoter and a promoterless
      cryIAc. Upon induction by 2 microM beta-estradiol, sequences encoding the
      selectable marker and cre sandwiched by two loxP sites were excised from the
      tomato genome, leading to activation of the downstream endotoxin gene cryIAc with
      high expression levels as shown by Northern blot and ELISA assay (250-790 ng g(
      1) fresh wt) in T(1) generation. For transgenic line with single transgenic loci,
      15% of T(1) progenies were revealed marker-free. This autoexcision strategy
      provides an effective approach to eliminate a selectable marker gene from
      transgenic tomato, thus expediting the public acceptance of genetically modified
      crop.

PMID- 16802103
TI  - Biodesulfurization of dibenzothiophene by growing cells of Gordonia sp. in batch
      cultures.
AB  - A new isolate, identified as Gordonia sp. ZD-7 by 16S rDNA sequence analysis,
      grew in n-hexadecane containing dibenzothiophene (DBT) which was degraded from
      2.8 mM to 0.2 mM within 48 h. Biodesulfurization could be repeatedly performed
      for more than 190 h, with average desulfurization rates of 5 mmol DBT kg cells
      (dry wt)(-1) h(-1).

PMID- 16802104
TI  - A novel in vitro cultivation system to produce and isolate soluble factors
      released from hyphae of arbuscular mycorrhizal fungi.
AB  - The Petri plate dual in vitro culture system for arbuscular mycorrhizal fungi
      (AMF) is ill-suited for the production and isolation of extraradically released
      soluble factors, thereby preventing the further characterization of such
      compounds. To overcome this technical bottleneck, we here describe a novel
      cultivation system using the standard AMF Glomus intraradices-carrot dual culture
      as a model. This new system is capable of producing soluble factors in copious
      amounts without any interference from host roots. The greatest advantages of this
      culture method include ease of handling and reusability of the culture vessel,
      thus making it a very cost effective system.

PMID- 16802105
TI  - Protective effects of beta-glucan extracted from Agaricus brasiliensis against
      chemically induced DNA damage in human lymphocytes.
AB  - beta-Glucans (BGs) are polysaccharides that are found in the cell walls of
      organisms such as bacteria, fungi, and some cereals. The objective of the present
      study was to investigate the genotoxic and antigenotoxic effects of BG extracted
      from the mushroom Agaricus brasiliensis (=Agaricus blazei Murrill ss. Heinemann).
      The mutagenic activity of BG was tested in single-cell gel electrophoresis assays
      with human peripheral lymphocytes. In addition, the protective effects against
      the cooked food mutagen 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and (+/
      )-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), which is the main metabolite of
      B[a]P, and against ROS (H(2)O(2))-induced DNA damage, were studied. The results
      showed that the compound itself was devoid of mutagenic activity, and that a
      significant dose-dependent protective effect against damage induced by hydrogen
      peroxide and Trp-P-2 occurred in the dose range 20-80 microg/ml. To investigate
      the prevention of Trp-P-2-induced DNA damage, a binding assay was carried out to
      determine whether BG inactivates the amine via direct binding. Since no such
      interactions were observed, it is likely that BG interacts with enzymes involved
      in the metabolism of the amine.

PMID- 16802106
TI  - Biochemical, ultrastructural and molecular characterization of the triphenyltin
      acetate (TPTA)-induced apoptosis in primary cultures of mouse thymocytes.
AB  - Triphenyltin acetate (TPTA), a triorganotin compound used in agriculture as a
      biocide, is immunotoxic in vivo and in vitro. The present study was undertaken to
      ascertain whether apoptosis might play a role in the TPTA toxicity in vitro.
      Mouse thymocyte primary cultures were exposed to 0, 4 and 8 micromol/L TPTA;
      methyl prednisolone (1 micromol/L) was used as a positive control. Cell aliquots
      were harvested after 0, 1, 2, 4, and 8 h and the presence of early or late
      apoptotic phenomena was checked by (a) morphological investigations; (b)
      spectrophotometric quantification of fragmented DNA and agarose gel
      electrophoresis; (c) cell flow cytofluorometry, using an annexin V-FITC kit; and
      (d) detection of in situ apoptosis by a colorimetric detection kit (Titer-Tacs).
      TPTA cytotoxicity was also evaluated using the trypan blue dye exclusion test.
      Morphological investigation indicated apoptosis and/or necrosis. After 8 h of
      incubation, cells exposed to 4 micromol/L TPTA showed an increase in DNA
      fragmentation (on electrophoresis), which was confirmed by spectrophotometry (p <
      0.05). Flow cytofluorometry pointed out an early (p < 0.05) increase of annexin V
      positive (apoptotic) cells in TPTA-exposed flasks, whereas at least partly
      contradictory, results were obtained with the Titer-Tacs kit. Overall, these
      results provide evidence that TPTA, at low concentrations (4 micromol/L) induces
      early and late apoptotic phenomena, whereas cells exposed to the highest
      concentrations (8 micromol/L) are likely to undergo necrosis rather than
      apoptosis.

PMID- 16802108
TI  - Ornithine transcarbamoylase deficiency presenting with acute liver failure.
AB  - Ornithine transcarbamoylase (OTC) deficiency is the most common hereditary urea
      cycle disorder. It is an X-linked recessive disorder that usually presents with
      encephalopathy and hyperammonaemia. We report a 14-month-old female carrier of
      OTC deficiency, who presented with a history of intermittent vomiting for 5 weeks
      and irritability and lethargy for 1 week. She was found to be in acute liver
      failure, with elevated transaminases, coagulopathy and a consistently low urea.
      Identifying an OTC mutation and ruling out other possible causes of acute hepatic
      failure confirmed the diagnosis. She was placed on low-protein diet supplemented
      with essential amino acids, and her liver enzymes, hyperammonaemia and
      coagulopathy corrected. Three other female patients have been reported with OTC
      deficiency presenting with severe cryptogenic hepatitis; our patient is unique in
      that the presentation of her disease was dominated by acute liver failure on a
      back ground of normal growth and development, no liver enlargement, and mild
      hyperammonaemia. OTC deficiency should be considered in the differential
      diagnosis of infants presenting with acute hepatocellular dysfunction, especially
      in females.

PMID- 16802107
TI  - Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or
      underdiagnosed disorder?
AB  - We present the third case of Niemann-Pick disease type C without neurological
      symptoms. The patient was a 53-year-old woman without significant prior health
      problems who died of acute pulmonary embolism. Autopsy findings of
      hepatosplenomegaly, lymphadenopathy and ceroid-rich foam cells raised the
      suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann-Pick
      disease type B; NPB) or a much rarer disorder, variant adult visceral form of
      Niemann-Pick disease type C (NPC). To verify the histopathological findings,
      SMPD1, NPC1 and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A
      (S666N) and c.2882A>G (N961S) were detected in the NPC1 gene. No pathogenic
      sequence variants were found either in the SMPD1 gene mutated in NPB or in NPC2
      gene. The pathogenicity of both NPC1 variants was supported by their location in
      regions important for the protein function. Both variations were not found in
      more than 300 control alleles. Identified sequence variations confirm the
      diagnosis of the extremely rare adult visceral form of Niemann-Pick disease type
      C, which is otherwise dominated by neurovisceral symptoms. Although only three
      patients have been reported, this (most probably underdiagnosed) form of NPC
      should be considered in differential diagnosis of isolated hepatosplenomegaly
      with foam cells in adulthood.

PMID- 16802109
TI  - Normal pregnancy outcome in L-2-hydroxyglutaric aciduria.
AB  - L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare progressive neurometabolic
      disease, defined as a characteristic clinical and radiological entity, mainly
      including mental retardation, cerebellar dysfunction and involvement of the
      subcortical white matter, cerebellum and basal ganglia on brain MRI. The
      biochemical hallmark is an increased urinary excretion of L-2-hydroxyglutaric
      acid. Management is only supportive. A child born to a Turkish mother in whom L-2
      HGA was previously diagnosed is reported. Although pregnancy was repeatedly
      advised against because of the important degree of mental retardation and the
      potential risk of a toxic effect on the embryo and/or fetus (at that time no
      reports of maternal L-2-HGA were available), she became pregnant at 30 years of
      age and the pregnancy passed uneventfully. On amniocentesis, performed at 5
      months of gestational age, elevated 2-hydroxyglutarate, previously shown to be
      almost exclusively the L-2-stereoisomer, was present in the amniotic fluid:
      27.5mu mol/L (controls <1.3; n=5). The child, not affected by the disease as
      shown by a normal urinary excretion of 2-hydroxyglutaric acid, was normal at
      birth. When last examined at the age of 3 years, both somatic and mental
      development were excellent. As the pathogenesis of the extensive brain damage in
      affected persons remains largely unknown, notwithstanding the recent
      identification of the mutated gene and the deficient enzyme, one can only
      speculate on the mechanism by which embryo and fetus from a L-2-HGA mother are
      spared, at least in this case.

PMID- 16802110
TI  - Age-related alterations of Apolipoprotein E and interleukin-1beta in the aging
      brain.
AB  - With normal aging, the brain undergoes several alterations including reduced
      neuronal functioning and alterations in glia homeostasis. An increase in
      inflammatory signaling has also been reported in some studies of the aging brain,
      with inflammation potentially mediating age-related changes in the brain.
      Apolipoprotein E (ApoE) is produced in the brain and has been shown to possess
      anti-inflammatory properties in a variety of paradigms. In the present study, we
      correlated age-related alterations in ApoE expression with age-related changes in
      the cytokine interleukin-1 beta (IL-1beta), in the brain of rats of increasing
      age. No significant alteration in ApoE mRNA was found in any region examined. A
      significant increase in IL-1beta mRNA with age was observed only in the cortex.
      Neither ApoE nor IL-1beta protein expression was significantly altered with age
      in the brain. A significant linear correlation between ApoE and IL-1beta mRNA was
      found in the cortex but not in the striatum or hippocampus. No correlation was
      found between ApoE and IL-1beta protein in any region examined. Taken together,
      these studies demonstrate that ApoE expression is not altered during normal brain
      aging, but suggest that there may be a relationship between ApoE and IL-1beta
      transcription in the cerebral cortex.

PMID- 16802111
TI  - Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions.
AB  - This study investigated the influence of chronically administered curcumin on
      normal ageing-related parameters: lipid peroxidation, lipofuscin concentration
      and intraneuronal lipofuscin accumulation, activities of the enzymes superoxide
      dismutase (SOD), glutathione peroxidase (GPx), and Na(+), K(+), -adenosine
      triphosphatase (Na(+), K(+), -ATPase) in different brain regions (cerebral
      cortex, hippocampus, cerebellum and medulla) of 6- and 24-month-old rats. In
      normal ageing, lipid peroxidation and lipofuscin concentration were found to
      increase with ageing, the activities of SOD, GPx and Na(+), K(+), -ATPase,
      however, decreased with ageing. Chronic curcumin treatment of both 6 and 24
      months old rats resulted in significant decreases in lipid peroxide and the
      lipofuscin contents in brain regions, the activities of SOD, GPx and Na(+), K(+),
      -ATPase however, showed significant increase in various brain regions. The
      present study, thus, demonstrated the antioxidative, antilipofusinogenesic and
      anti-ageing effects of curcumin in the brain.

PMID- 16802112
TI  - Chronic treatment with physiological doses of estradiol affects the GH-IGF-1 axis
      and fat metabolism in young and middle-aged ovariectomized rats.
AB  - Estrogen deficiency may be partly responsible for the metabolic syndrome and the
      condition may be reversible with hormone replacement therapy. However, after the
      heart and estrogen/progestin replacement study and the women's health initiative
      study the prospect of HRT on CVD has changed dramatically. As the pituitary and
      the liver are targets for estrogen action we assessed the effect of ovariectomy
      (OVX) and long-term (3 months) estradiol (E2) treatment by means of
      subcutaneously (s.c.) implanted silastic capsules on pituitary and liver function
      in young and middle-aged female rats. Our results demonstrate that triglyceride
      serum levels increased, whereas insulin-like growth factor-1 (IGF-1), high
      density lipoprotein cholesterol (HDL), and glucose levels decreased during the
      transition from young to middle-age. E2 treatment increased dose-independently
      growth hormone (GH) secretion. IGF-1 levels were increased upon OVX in middle
      aged rats and the high dose of E2 decreased IGF-1 concentrations in both age
      groups. Cholesterol concentrations increased after OVX and were attenuated by E2
      administration in middle-aged rats. Both, low density lipoprotein cholesterol
      (LDL) and HDL levels raised after castration and both parameters decreased in
      response to E2 in young and middle-aged rats. Glucose serum concentrations
      decreased after E2 treatment in all animals. Taken together, our results clearly
      demonstrate that the pituitary and the liver metabolism of middle-aged rats
      remain susceptible to the influence of OVX and E2 treatment.

PMID- 16802113
TI  - Carnitine and lipoic acid alleviates protein oxidation in heart mitochondria
      during aging process.
AB  - Oxidative modification alters the function of proteins and is thought to play an
      important role in the decline of cellular function during aging process. In the
      present study, we have evaluated the levels of oxidant production, protein
      oxidation, reduced and oxidized glutathione in young, middle aged and aged rats.
      The animals were divided into six groups, each group consisting of six animals
      each. Groups I and II were young rats, Groups III and IV were middle-aged rats
      and Groups V and VI were aged rats. Groups II, IV and VI were treated with
      carnitine (300 mg/kg bw) and Dl-alpha-Lipoic acid (100 mg/kg bw) for 28 days.
      Statistical significance was carried out using ANOVA. There was a significant
      reduction in the levels of reduced glutathione and Redox ratio (P<0.05) in aged
      rats whereas elevation in the levels of oxidant production, protein carbonyls,
      advanced oxidation protein products and oxidized glutathione were observed. Co
      supplementation of carnitine and lipoic acid improved these levels to near
      normalcy. Thus we conclude that the utilization of carnitine and lipoic acid will
      lead to an improvement in the quality of living during the later stages of life
      by preventing free radical induced damage to the proteins.

PMID- 16802114
TI  - Oxidative stress and DNA single strand breaks in skeletal muscle of aged rats:
      role of carnitine and lipoicacid.
AB  - The exposure of biological system to various conditions of oxidative stress is
      the major contributor for aging process. Oxidative stress in turn increases the
      cellular levels of oxidatively modified proteins, lipids and nucleic acids
      resulting in a loss of physical activity and metabolic integrity. In this study,
      we evaluated the role of L-carnitine and DL-alpha-lipoic acid in minimizing
      oxidant generation and macromolecular damage in skeletal muscle of aged rats. We
      found that the oxidant generation was increased in aged rat skeletal muscle when
      compared to young rats. There was a simultaneous increase in the levels of lipid
      peroxidation, protein carbonyl content and DNA strand breaks in aged rat skeletal
      muscle. Administration of L-carnitine (300 mg/kg body wt/day) and DL-alpha-lipoic
      acid (100 mg/kg body wt/day) to aged rats for 30 days, decreased the oxidant
      generation, lipid peroxidation, protein carbonylation and DNA strand breaks. We
      concluded that co-administration of carnitine and lipoic acid to aged rats has
      the potential to prevent oxidative stress mediated macromolecular damage in
      skeletal muscle of aged rats by their putative role as efficient antioxidants.

PMID- 16802115
TI  - The failure of dose-response models to predict low dose effects: a major
      challenge for biomedical, toxicological and aging research.
AB  - Recent detailed evaluations of the pharmacological, toxicological, and
      biogerontological literature indicate that the hormetic dose-response is quite
      common and highly generalizable by biological model, endpoint, and chemical
      class. Head-to-head comparisons of the hormetic model with the traditional
      threshold model have revealed the hormetic model to occur with considerably
      greater frequency in the biomedical literature. Despite these developments, the
      history of both pharmacology and toxicology reflects a strong acceptance and
      centralizing of the threshold model concept while profoundly marginalizing of the
      hormetic dose-response. This commentary will address why the biomedical community
      especially those in the areas of pharmacology and toxicology made an incorrect
      judgment that the most fundamental nature of the dose-response was threshold
      rather than hormetic and why this conclusion has continued to dominate these
      fields and their numerous applications despite convincing evidence to the
      contrary. These findings have particular relevance to the area of biogerontology
      since this discipline often resides at the pharmacological-toxicological
      interface.

PMID- 16802116
TI  - WITHDRAWN: "Florigenesis": a novel pathway of plant regeneration in soybean.
AB  - Ahead of Print article withdrawn by publisher

PMID- 16802117
TI  - Transgenic peas (Pisum sativum) expressing polygalacturonase inhibiting protein
      from raspberry (Rubus idaeus) and stilbene synthase from grape (Vitis vinifera).
AB  - The pea (Pisum sativum L.) varieties Baroness (United Kingdome) and Baccara
      (France) were transformed via Agrobacterium tumefaciens-mediated gene transfer
      with pGPTV binary vectors containing the bar gene in combination with two
      different antifungal genes coding for polygalacturonase-inhibiting protein (PGIP)
      from raspberry (Rubus idaeus L.) driven by a double 35S promoter, or the stilbene
      synthase (Vst1) from grape (Vitis vinifera L.) driven by its own elicitor
      inducible promoter. Transgenic lines were established and transgenes combined via
      conventional crossing. Resveratrol, produced by Vst1 transgenic plants, was
      detected using HPLC and the PGIP expression was determined in functional
      inhibition assays against fungal polygalacturonases. Stable inheritance of the
      antifungal genes in the transgenic plants was demonstrated.

PMID- 16802119
TI  - Optional deductibles in social health insurance systems: findings from Germany.
AB  - A fundamental aspect of the German health insurance system is the principle of
      solidarity. At the same time, it is possible for certain socio-economic groups to
      opt out of the otherwise compulsory system. To determine whether rates
      incorporating deductibles are compatible with the principles of solidarity and
      have the ability to heighten the appeal of statutory health insurance (SHI) funds
      compared with private health insurance companies, Germany's third largest SHI
      fund, Techniker Krankenkasse, implemented a pilot scheme involving the use of
      deductibles. Preliminary scientific evaluations of the pilot scheme indicate
      three main results for these deductibles: Firstly, they are compatible with the
      principles of solidarity in the statutory health insurance system; secondly, they
      provide an effective means of preventing defection to private health insurance
      companies and thirdly, they reduced the volume of insurance claims (moral
      hazard).

PMID- 16802118
TI  - Genes expressed during the development and ripening of watermelon fruit.
AB  - A normalized cDNA library was constructed using watermelon flesh mRNA from three
      distinct developmental time-points and was subtracted by hybridization with leaf
      cDNA. Random cDNA clones of the watermelon flesh subtraction library were
      sequenced from the 5' end in order to identify potentially informative genes
      associated with fruit setting, development, and ripening. One-thousand and forty
      six 5'-end sequences (expressed sequence tags; ESTs) were assembled into 832 non
      redundant sequences, designated as "EST-unigenes". Of these 832 "EST-unigenes",
      254 ( approximately 30%) have no significant homology to sequences published so
      far for other plant species. Additionally, 168 "EST-unigenes" ( approximately
      20%) correspond to genes with unknown function, whereas 410 "EST-unigenes" (
      approximately 50%) correspond to genes with known function in other plant
      species. These "EST-unigenes" are mainly associated with metabolism, membrane
      transport, cytoskeleton synthesis and structure, cell wall formation and cell
      division, signal transduction, nucleic acid binding and transcription factors,
      defense and stress response, and secondary metabolism. This study provides the
      scientific community with novel genetic information for watermelon as well as an
      expanded pool of genes associated with fruit development in watermelon. These
      genes will be useful targets in future genetic and functional genomic studies of
      watermelon and its development.

PMID- 16802120
TI  - [Unclear atrophy of the optic nerve].

PMID- 16802121
TI  - Soft material-based microculture system having air permeable cover sheet for the
      protoplast culture of Nicotiana tabacum.
AB  - In plant cell culture, the delivery of nutrition and gas (mainly oxygen) to the
      cells is the most important factor for viability. In this paper, we propose a
      polydimethylsiloxane (PDMS)-based microculture system that is designed to have
      good aeration. PDMS is known to have excellent air permeability, and through the
      experimental method, we investigated the relation between the degree of air
      delivery and the thickness of the PDMS sheet covering the culture chamber. We
      determined the proper thickness of the cover sheet, and cultured protoplasts of
      Nicotiana tabacum in a culture chamber covered with a PDMS sheet having thickness
      of 400 microm. The cells were successfully divided, and lived well inside the
      culture chamber for 10 days. In addition, protoplasts were cultured inside the
      culture chambers covered with the cover glass and the PDMS sheet, respectively,
      and the microcolonies were formed well inside the PDMS covered chamber after 10
      days.

PMID- 16802122
TI  - An eco-friendly and sustainable process for enzymatic hydrolysis of penicillin G
      in cloud point system.
AB  - Enzymatic hydrolysis of penicillin G by immobilized penicillin acylase in a
      nonionic surfactant mediated cloud point system was presented. The effect of the
      operation parameters on equilibrium pH of this enzymatic hydrolysis process
      without pH control was examined. A relatively high equilibrium pH in cloud point
      system without pH control can be obtained. The feasibility of recycling
      utilization of the nonionic surfactant, a novel green solvent, was also
      investigated experimentally. Enzymatic hydrolysis of penicillin G in a discrete
      semi-batch mode, which simulates a semi-continuous process, envisages a
      completely eco-friendly, sustainable and efficient process for production of 6
      aminopenicillanic acid.

PMID- 16802123
TI  - Bio-assay based on single molecule fluorescence detection in microfluidic
      channels.
AB  - A rapid bioassay is described based on the detection of colocalized fluorescent
      DNA probes bound to DNA targets in a pressure-driven solution flowing through a
      planar microfluidic channel. By employing total internal reflection excitation of
      the fluorescent probes and illumination of almost the entire flow channel, single
      fluorescent molecules can be efficiently detected leading to the rapid analysis
      of nearly the entire solution flowed through the device. Cross-correlation
      between images obtained from two spectrally distinct probes is used to determine
      the target concentration and efficiently reduces the number of false positives.
      The rapid analysis of DNA targets in the low pM range in less than a minute is
      demonstrated.

PMID- 16802124
TI  - Interfacial behavior of sulforhodamine 101 at the polarized water/1,2
      dichloroethane interface studied by spectroelectrochemical techniques.
AB  - The transfer mechanism of an amphoteric rhodamine, sulforhodamine 101 (SR101),
      across the polarized water/1,2-dichloroethane (DCE) interface was investigated
      using cyclic voltammetry, differential voltfluorometry and potential-modulated
      fluorescence (PMF) spectroscopy. The voltammetric response for the ion transfer
      of SR101 monoanion from water to DCE was observed as the diffusion-controlled
      transfer process. An unusual voltammetric response was found at 0.15 V more
      negative than the formal transfer potential of SR101(-) (deltaW(O)phi degrees')
      in the cyclic voltammogram and voltfluorogram. The frequency dependence of the
      PMF responses confirmed the presence of the adsorption processes at negative
      potentials. In addition, a further transient adsorption step was uncovered at
      deltaW(O)phi degrees'. The interfacial mechanism of SR101 is discussed by
      comparing the results obtained from each technique.

PMID- 16802125
TI  - Late myocardial enhancement assessed by 64-MSCT in reperfused porcine myocardial
      infarction: diagnostic accuracy of low-dose CT protocols in comparison with
      magnetic resonance imaging.
AB  - The purpose was to assess the practicability of low-dose CT imaging of late
      enhancement in acute infarction. Following temporary occlusion of the second
      diagonal branch, seven pigs were studied by multislice computed tomography (MSCT)
      and magnetic resonance imaging (MRI). Thus, 64-slice CT was performed at 3, 5, 10
      and 15 min following the injection of contrast medium according to a bolus/low
      flow protocol. Standard parameters of 120 kV and 800 mAs were compared with 80 kV
      and 400 mAs in various combinations. Infarct volumes were assessed as percentage
      of the ventricle for both MSCT and MR images. CT density values for viable and
      infarcted myocardium were obtained and image quality assessed. Mean infarct
      volume as measured by MRI was 12.33+/-7.06%. MSCT achieved best correlation of
      volumes at 5 and 10 min. Whilst lowering of tube current resulted in poor
      correlation, tube voltage did not affect accuracy of infarct measurement (r
      (2)=0.92 or 0.93 at 5 min, 800 mAs and 80 or 120 kV). In terms of image quality,
      greater image noise with 80 kV was compensated by significantly better contrast
      enhancement between viable and non-viable myocardium at lower voltage. Myocardial
      viability can accurately be assessed by MSCT at 80 kV, which ensures higher
      contrast for late enhancement and yields good correlation with MRI.

PMID- 16802126
TI  - MR imaging of osteochondral grafts and autologous chondrocyte implantation.
AB  - Surgical articular cartilage repair therapies for cartilage defects such as
      osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or
      matrix associated autologous chondrocyte transplantation (MACT) are becoming more
      common. MRI has become the method of choice for non-invasive follow-up of
      patients after cartilage repair surgery. It should be performed with cartilage
      sensitive sequences, including fat-suppressed proton density-weighted T2 fast
      spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences,
      which provide good signal-to-noise and contrast-to-noise ratios. A thorough
      magnetic resonance (MR)-based assessment of cartilage repair tissue includes
      evaluations of defect filling, the surface and structure of repair tissue, the
      signal intensity of repair tissue and the subchondral bone status. Furthermore,
      in osteochondral autografts surface congruity, osseous incorporation and the
      donor site should be assessed. High spatial resolution is mandatory and can be
      achieved either by using a surface coil with a 1.5-T scanner or with a knee coil
      at 3 T; it is particularly important for assessing graft morphology and
      integration. Moreover, MR imaging facilitates assessment of complications
      including periosteal hypertrophy, delamination, adhesions, surface incongruence
      and reactive changes such as effusions and synovitis. Ongoing developments
      include isotropic 3D sequences, for improved morphological analysis, and in vivo
      biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging,
      which make functional analysis of cartilage possible.

PMID- 16802127
TI  - Bringing palliative care to a Canadian cancer center: the palliative care program
      at Princess Margaret Hospital.
AB  - It is increasingly recognized that complete care of the patient with cancer
      includes palliative care, which is applicable early in the course of illness, in
      conjunction with life-prolonging treatment. Princess Margaret Hospital (PMH) is
      Canada's largest center for cancer care and research, and it is an international
      referral center for patients with cancer. The Palliative Care Program at PMH has
      developed into a comprehensive clinical, educational, and research program, with
      an acute palliative care unit, daily palliative care clinics, a cancer pain
      clinic, and a consultation service that sees urgent consultations on a same-day
      basis in inpatient and outpatient areas. We will describe the components,
      successes, and challenges of our program, which may be useful for others, who are
      developing palliative care programs in an academic setting.

PMID- 16802128
TI  - Clinical and economic impact of epoetin in adjuvant-chemotherapy for breast
      cancer.
AB  - INTRODUCTION: Anaemia is a common toxicity in cancer patients and epoetins (EPOs)
      are now an established treatment. The economic profile of EPO treatment was
      assessed in patients with breast cancer treated by adjuvant-chemotherapy.
      MATERIALS AND METHODS: Two strategies were compared: without treatment by EPO and
      with the possible use of treatment by EPO (epoetin alfa) when required. The
      clinical effectiveness criterion was time adjusted to quality of life and
      economic data included only direct medical costs. MAIN RESULTS: One hundred
      ninety-two patients were included. In the group with the strategy containing the
      possible use of EPO, 45.5% of patients effectively received EPO. A significant
      difference in the haemoglobin level profile over time was observed which provided
      a significant overall benefit of 0.0052 (p<10(-4)) quality-adjusted life year
      (QALY) associated with an extra cost of <euro>1,615 (p<10(-4)). In the base case
      analysis, the cost per added QALY was estimated as <euro>310,577 with the
      strategy containing the possible use of EPO. CONCLUSION: This robust result seems
      to be unacceptable, but the only relevant point of discussion might be the level
      of acceptable incremental cost-effectiveness ratio (ICER) for a patient.

PMID- 16802129
TI  - Clonal variability of group B Streptococcus among different groups of carriers in
      southern Israel.
AB  - A high prevalence of maternal group B Streptococcus (GBS) carriage and an
      extremely low incidence of invasive neonatal disease have been reported from
      southern Israel. In order to obtain insight into this discrepancy, this study was
      performed to determine the population structure of GBS from asymptomatic pregnant
      women living in this area. Seventy-two strains from maternal GBS carriers were
      characterized using multilocus sequence typing (MLST). Epidemiologic
      characteristics of the carriers and their newborns, including demographic
      variables, obstetric status, and general health parameters, were collected by
      means of a postpartum interview and a review of the relevant medical records. The
      MLST analysis grouped the bacteria into six different lineages (clonal
      complexes). Lineage ST-2 was prevalent among Bedouin-Arabs (p=0.01) and lineage
      ST-22 among Jews (p=0.001). Lineage ST-17 was prevalent among carriers who
      emigrated after 1997 from western nations of the former USSR (p<0.001). Lineage
      ST-22 was associated with carriage of surface-protein C (p=0.01) and lineage ST
      17 with surface-protein R (p<0.01). Lineage ST-2 was prevalent among consumers of
      antibiotics (p=0.02) and was associated with erythromycin-resistant strains
      (p<0.001). Each subgroup of the southern Israeli maternal population has a
      different distribution of GBS clones. The clones prevalent among the Bedouin
      Arabs and the Jews are known to be of low virulence. Lineage ST-17, which is
      associated with invasive disease, is prevalent among women who emigrated from
      western Soviet nations. Therefore, a different policy of GBS prophylaxis,
      resembling the one executed in endemic areas, should be considered in this
      population.

PMID- 16802130
TI  - Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the
      initiation and adjustment of therapy. A consensus statement from the American
      Diabetes Association and the European Association for the Study of Diabetes.

PMID- 16802131
TI  - Effects of dipeptidyl peptidase IV on the satiety actions of peptide YY.
AB  - AIMS/HYPOTHESIS: Dipeptidyl peptidase IV (DP IV) inhibitors are currently being
      developed to prolong the biological activity of insulinotropic peptides as a
      novel approach in the treatment of diabetes. We hypothesised that DP IV
      inhibition could attenuate the satiety actions of peptide YY (PYY) by altering
      the conversion of PYY(1-36) to PYY(3-36). MATERIALS AND METHODS: The effects of
      PYY delivered by osmotic mini-pumps were assessed in rats treated with a DP IV
      inhibitor and in a rat model deficient in DP IV. RESULTS: Pharmacological levels
      of total PYY were found in the circulation after the exogenous administration of
      PYY(3-36). While both PYY(1-36) and PYY(3-36) reduced food intake in normal rats,
      PYY(1-36) was ineffective in rats deficient in DP IV. When re-fed after a 24-h
      fast, DP IV-deficient rats exhibited higher food intake and weight gain than
      normal rats. Moreover, unlike controls, there was no postprandial increase in PYY
      levels in DP IV-deficient rats. Despite these findings, administration of a DP IV
      inhibitor, Pro-boroPro, did not alter the acute anorectic effects of exogenous
      PYY(1-36) in normal rats. This could be the result of the protection of other
      appetite regulatory peptides or the generation of PYY(3-36) by remaining DP IV
      activity or other dipeptidyl peptidases. CONCLUSIONS/INTERPRETATION: Although DP
      IV inhibition with Pro-boroPro attenuated the generation of PYY(3-36), our
      results indicate that short-term DP IV inhibition does not eliminate the satiety
      actions of exogenously administered PYY(1-36) at the doses tested.

PMID- 16802132
TI  - Direct evidence of attempted beta cell regeneration in an 89-year-old patient
      with recent-onset type 1 diabetes.
AB  - AIMS/HYPOTHESIS: We investigated whether there was evidence of attempted beta
      cell regeneration in the pancreas obtained from a patient with recent-onset type
      1 diabetes, and if so by what mechanism this occurred. SUBJECTS, MATERIALS AND
      METHODS: We examined pancreas tissue from a lean 89-year-old patient (BMI 18.0
      kg/m(2)) with recent-onset type 1 diabetes who had had a distal pancreatectomy to
      remove a low-grade pancreatic intraepithelial neoplasia. RESULTS: In the tumour
      free tissue, the fractional beta cell area was 0.54+/-0.2% of pancreas area
      (about one-third of that in non-diabetic humans). CD3-positive T lymphocytes and
      macrophages had infiltrated the majority of the islets. Subclassification of the
      T cell population revealed a predominance of CD8-positive cells over CD4-positive
      cells. Beta cell apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick-end labelling [TUNEL] staining) was greatly increased, consistent
      with ongoing immune-mediated beta cell destruction. There was also a marked
      increase (more than approximately 100-fold) in the frequency of beta cell
      replication (0.69+/-0.15% Ki67-positive beta cells) in all blocks examined.
      CONCLUSIONS/INTERPRETATION: The present report provides direct evidence of
      attempted beta cell regeneration through the mechanism of beta cell replication
      in a case of newly diagnosed type 1 diabetes, and affirms that beta cell
      apoptosis is an important mechanism for beta cell loss in type 1 diabetes.

PMID- 16802133
TI  - Early vitrectomy for fundus-obscuring dense vitreous haemorrhage from presumptive
      retinal tears.
AB  - BACKGROUND: Published literature on the management of patients with fundus
      obscuring dense vitreous haemorrhage due to presumptive retinal tears is sparse
      and advocates waiting for spontaneous resolution. Surgery is indicated only when
      a definite retinal tear or retinal detachment is identified. METHODS: A
      retrospective review of all patients who underwent early vitrectomy for vitreous
      haemorrhage associated with posterior vitreous detachment was carried out. A
      comparison of initial visual acuity versus final visual acuity after vitrectomy
      was performed. The number of eyes that were found to have retinal tears and
      retinal detachment were documented. Initial and final Snellen acuities were used
      for statistical analysis. Categorical data were analysed using Fisher's exact
      test and statistical significance was considered to be p < 0.05. RESULTS: Sixteen
      eyes were identified and all these patients presented or were referred soon after
      the onset of vitreous haemorrhage. Associated ocular pathology (choroidal
      neovascular membrane, retinal branch vein occlu-sion, macroaneurysm) was
      suspected to be the source of the haemorrhage in 4 eyes. Vitrectomy was carried
      out in 12 eyes soon after presentation (mean time 6.3 days, range 1-28 days).
      Nineteen retinal breaks were seen in these eyes and 5 eyes had more than two
      breaks. None of the eyes were found to have proliferative vitreoretinopathy at
      the time of surgery. Two eyes needed repeat surgery for new retinal breaks.
      Excluding the eyes found to have an ocular pathology as the cause of vitreous
      haemorrhage, the mean visual acuity improved from hand movements to 6/12 (p <
      0.001). CONCLUSIONS: Early vitrectomy for spontaneous dense fundus-obscuring
      vitreous haemorrhage and posterior vitreous detachment is safe. Since the number
      of patients in this study was small, a prospective randomised controlled study
      comparing early versus late vitrectomy is needed to see whether early surgery
      also prevents proliferative vitreoretinopathy formation.

PMID- 16802134
TI  - Termination and beyond: acetylcholinesterase as a modulator of synaptic
      transmission.
AB  - Termination of synaptic transmission by neurotransmitter hydrolysis is a
      substantial characteristic of cholinergic synapses. This unique termination
      mechanism makes acetylcholinesterase (AChE), the enzyme in charge of executing
      acetylcholine breakdown, a key component of cholinergic signaling. AChE is now
      known to exist not as a single entity, but rather as a combinatorial complex of
      protein products. The diverse AChE molecular forms are generated by a single gene
      that produces over ten different transcripts by alternative splicing and
      alternative promoter choices. These transcripts are translated into six different
      protein subunits. Mature AChE proteins are found as soluble monomers, amphipatic
      dimers, or tetramers of these subunits and become associated to the cellular
      membrane by specialized anchoring molecules or members of other heteromeric
      structural components. A substantial increasing body of research indicates that
      AChE functions in the central nervous system go far beyond the termination of
      synaptic transmission. The non-enzymatic neuromodulatory functions of AChE affect
      neurite outgrowth and synaptogenesis and play a major role in memory formation
      and stress responses. The structural homology between AChE and cell adhesion
      proteins, together with the recently discovered protein partners of AChE, predict
      the future unraveling of the molecular pathways underlying these multileveled
      functions.

PMID- 16802135
TI  - [Regeneration instead of reparation: a critical review of the autogenous bone
      transplant as "golden standard" of reconstructive oral surgery].
AB  - Autogenous bone transfer is still regarded as the "golden standard" for many
      indications in oral and cranio-maxillofacial surgery. In this overview, the
      status of the autogenous bone is re-evaluated under consideration of current
      research results, clinical long-term studies, risks and safety of the patient as
      well as the costs. Due to the further development of modern bone substitute
      materials, which reveal in parts superior long-term results for special
      indications, the routine use of autogenous bone has to be critically reviewed.

PMID- 16802136
TI  - Identification of a glycine-rich protein from the tick Rhipicephalus
      haemaphysaloides and evaluation of its vaccine potential against tick feeding.
AB  - A cDNA coding a glycine-rich protein was identified from the Rhipicephalus
      haemaphysaloides tick. The cDNA named here as RH50 was 1,823 bp, including a
      single open reading frame (ORF) of 1,518 nucleotides. The ORF encodes a
      polypeptide of 506 amino acid residues with a size of 50 kDa, as calculated by a
      computer. The predicted amino acid sequence of RH50 showed a low homology to
      sequences of some known extracellular matrix-like proteins. The native protein
      was identified in both the fed tick salivary gland lysates and extracts of cement
      material using the serum against the recombinant protein. Reverse transcription
      polymerase chain reaction results showed that RH50 mRNA was only transcribed in
      partially fed tick salivary glands, not in unfed tick salivary glands or
      partially fed tick midgut, fat body, or ovary. The differential expression of
      RH50 protein in fed tick salivary glands was confirmed by immunofluorescence. The
      low attachment rate both in the adult and nymphal tick, and the high mortality of
      immature ticks (nymph) feeding on recombinant RH50-immunized rabbits were found.
      These results show that the RH50 protein could be a useful candidate for anti
      tick vaccine development.

PMID- 16802137
TI  - The second cysteine protease inhibitor, EhICP2, has a different localization in
      trophozoites of Entamoeba histolytica than EhICP1.
AB  - The genome of Entamoeba histolytica contains two genes encoding inhibitors of
      cysteine proteases of the chagasin family. In contrast to that of EhICP1, the
      derived primary structure of the second inhibitor, EhICP2, possesses a typical N
      terminal signal sequence. Processed EhICP2 is as weakly related to amoebiasin-1
      (27% identity) as to chagasin (identity 30%), indicating a different evolutionary
      origin of both amebic genes. By Northern blots, we confirmed the expression of
      the ehicp2 gene, and in Western blots, the presence of the 11.5-kDa protein in
      trophozoite extracts was demonstrated. The inhibitor localized to large
      intracellular structures clearly differs from those containing EhICP1 as shown by
      indirect immunofluorescence. Recombinant EhICP2 significantly inhibited the
      cysteine protease activity of the amebic cell extract but with a lower extent
      than EhICP1. An overlay assay using a crude trophozoite extract demonstrated
      binding affinity of the amebic cysteine protease EhCP1 to EhICP2.

PMID- 16802138
TI  - Alternatives to systemic steroid therapy for refractory immune-mediated inner ear
      disease: A physiopathologic approach.
AB  - Immune-mediated inner ear disease (IMIED) is one of the few forms of reversible
      sensorineural hearing loss. Corticosteroids-responsive patients are usually
      associated with hearing improvement. Due to the long clinical course of IMIED
      that frequently present recurrences (hearing loss and vertigo), alternatives to
      corticosteroids such as methotrexate and recently TNF-alpha blockers have been
      proposed. Likewise new procedures for delivering corticosteroids to the inner ear
      have been developed. The aim of this article is to assess the efficacy of
      methotrexate and transtympanic 6-methylprednisolone in refractory IMIED. From a
      database of 200 patients affected by IMIED, 16 selected patients with refractory
      disease were included in the present study. Five patients were treated with
      methotrexate and 11 by means of transtympanic injection of 6-methylprednisolone.
      All patients treated with methotrexate had an improvement in their vestibular
      symptoms. However, hearing loss did not improve. Most patients treated with local
      6-methylprednisolone (68.75%) showed an improvement in hearing loss and
      vestibular symptoms. Methotrexate has been shown to be ineffective in maintaining
      long-term remissions of hearing relapses although patients presented an
      improvement in vestibular symptoms. However, transtympanic 6-methylprednisolone
      has been shown to be a safe, easy and useful therapy in refractory IMIED and it
      may actually become the first-line treatment for these patients based on the
      existence of glucocorticoid receptors and the possible targets of immune-mediated
      damage within the inner ear.

PMID- 16802139
TI  - The role of sleep position in obstructive sleep apnea syndrome.
AB  - We analyzed the role of sleep position in obstructive sleep apnea syndrome
      (OSAS). The polysomnograms of 120 patients with sleep apnea syndrome were
      analyzed. We associated the apnea hypopnea index (AHI) of the supine position
      with the AHI of the other positions. Patients were stratified in a group of
      positional patients (PP) (AHI supine >or= 2 x AHI other positions) and a group of
      non-positional patients (NPP). In 55.8% of our patients, OSAS was position
      dependent. PP patients were significantly (6.7 years) younger. BMI and AHI were
      higher in the NPP group, but the difference was not significant. Level of
      obstruction in the upper airway (retropalatinal vs retrolingual vs both levels)
      as assessed by sleep endoscopy was not significantly different between the two
      groups. Total sleep time (TST) was equal in both groups, but the average time in
      supine position was 37 min longer in the PP group. This study confirms the
      finding that in more than 50% of patients, OSAS is position dependent. Apart from
      age, no patient characteristics were found indicating the position dependency.
      Overall AHI does not identify positional OSAS.

PMID- 16802140
TI  - Metastatic Ewing sarcoma masquerading as olfactory neuroblastoma.
AB  - Ewing sarcoma is a malignant tumor of bone that rarely spreads to the head and
      neck. We describe an unusual case of metastatic Ewing sarcoma involving the
      calvarium mimicking olfactory neuroblastoma, an uncommon neuroectodermal tumor of
      the anterior skull base. Pertinent clinical, radiological, and pathologic
      features of these tumors are described, with particular attention to their
      imaging characteristics.

PMID- 16802141
TI  - A novel deletion in TNNI2 causes distal arthrogryposis in a large Chinese family
      with marked variability of expression.
AB  - Distal arthrogryposis (DA) is composed of a group of clinically and genetically
      heterogeneous disorders, characterized by multiple congenital contractures of the
      limbs. Point mutations in three genes encoding contractile fast-twitch myofibers,
      TPM2, TNNI2 and TNNT3, were recently identified in DA type 1 (DA1; MIM 108120)
      and DA type 2B (DA2B; MIM 601680). We have described a large Chinese DA family in
      which different individuals had phenotypes similar to DA1 or DA2B. To map the
      disease locus in this family, two-point linkage analysis was first performed
      using microsatellite markers selected from the genomic regions close to the TPM2,
      TNNI2/TNNT3 and TNNC2 genes. A positive LOD score of 3.61 at theta = 0 was
      obtained with the marker close to the TNNI2/TNNT3 genes, corresponding to the
      genetic mapping site of DA2B. Direct sequencing of the PCR-amplified DNA fragment
      spanning exon 8 of the TNNI2 gene showed a heterozygous deletion, c.523_525delAAG
      (p.K175del), in the proband. This novel mutation was confirmed to cosegregate
      with the DA phenotype in affected individuals but not detected in all unaffected
      individuals of the family and not in 50 healthy controls. In summary, we have
      found a novel TNNI2 mutation in a Chinese family with DA2B. Our work represents
      the first report on the link between TNNI2 and the DA phenotype in Chinese.

PMID- 16802142
TI  - Mucocele of the sphenoid sinus.
AB  - The sphenoid sinus is the least common site of mucocele of all paranasal sinuses.
      It is very rare in children, especially in those younger than 12 years when
      pneumatization of the sphenoid sinus is completed. We report a case of
      histologically proven sphenoidal mucocele in a 5-year-old child. The child
      presented with an acute onset of significant visual impairment and headache. His
      vision gradually improved after trans-nasal sphenoidotomy and drainage of the
      sinus content with return of complete normal baseline vision after 2 months.

PMID- 16802143
TI  - Myelination process in preterm subjects with periventricular leucomalacia
      assessed by magnetization transfer ratio.
AB  - BACKGROUND: Magnetization transfer imaging assesses the myelination status of the
      brain. OBJECTIVES: To study the progress of myelination in children with
      periventricular leucomalacia (PVL) by measuring the magnetization transfer ratio
      (MTR) and to compare the MTR values with normal values. MATERIALS AND METHODS:
      Brain MTR in 28 PVL subjects (16 males, 12 females, gestational age 30.7+/-2.5
      weeks, corrected age 3.1+/-2.9 years) was measured using a 3D gradient echo
      sequence (TR/TE 32/8 ms, flip angle 60 degrees, 4 mm/2 mm overlapping sections)
      without and with magnetization transfer prepulse and compared with normal values
      for preterm subjects. RESULTS: MTR of white-matter structures followed a
      monoexponential function model (y=A-B*exp(-x/C)) while the thalamus and caudate
      nucleus had a poor goodness of fit. MTR of the splenium of the corpus callosum
      reached a final value lower than normal (0.67 versus 0.70) at a younger age
      [t(99%) at 10.32 versus 18.90 months; P<0.05]. MTR of the normal-appearing
      occipital white matter and of the genu of the corpus callosum reached a normal
      final MTR but at a younger age than normal preterm infants [t(99%) at 8.51 versus
      14.50 months and 12.51 versus 20.85 months, respectively]. CONCLUSION: In PVL
      subjects, myelination of the splenium is characterized by early arrest and
      deficient maturation. Accelerated myelination in unaffected white matter might
      suggest a compensatory process of reorganization.

PMID- 16802144
TI  - Audience effects on food caching in grey squirrels (Sciurus carolinensis):
      evidence for pilferage avoidance strategies.
AB  - If food pilferage has been a reliable selection pressure on food caching animals,
      those animals should have evolved the ability to protect their caches from
      pilferers. Evidence that animals protect their caches would support the argument
      that pilferage has been an important adaptive challenge. We observed naturally
      caching Eastern grey squirrels (Sciurus carolinensis) in order to determine
      whether they used any evasive tactics in order to deter conspecific and
      heterospecific pilferage. We found that grey squirrels used evasive tactics when
      they had a conspecific audience, but not when they had a heterospecific (corvid)
      audience. When other squirrels were present, grey squirrels spaced their caches
      farther apart and preferentially cached when oriented with their backs to other
      squirrels, but no such effect was found when birds were present. Our data provide
      the first evidence that caching mammals are sensitive to the risk of pilferage
      posed by an audience of conspecifics, and that they utilise evasive tactics that
      should help to minimise cache loss. We discuss our results in relation to recent
      theory of reciprocal pilferage and compare them to behaviours shown by caching
      birds.

PMID- 16802145
TI  - Dogs recall their owner's face upon hearing the owner's voice.
AB  - We tested whether dogs have a cross-modal representation of human individuals. We
      presented domestic dogs with a photo of either the owner's or a stranger's face
      on the LCD monitor after playing back a voice of one of those persons. A voice
      and a face matched in half of the trials (Congruent condition) and mismatched in
      the other half (Incongruent condition). If our subjects activate visual images of
      the voice, their expectation would be contradicted in Incongruent condition. It
      would result in the subjects' longer looking times in Incongruent condition than
      in Congruent condition. Our subject dogs looked longer at the visual stimulus in
      Incongruent condition than in Congruent condition. This suggests that dogs
      actively generate their internal representation of the owner's face when they
      hear the owner calling them. This is the first demonstration that nonhuman
      animals do not merely associate auditory and visual stimuli but also actively
      generate a visual image from auditory information. Furthermore, our subject also
      looked at the visual stimulus longer in Incongruent condition in which the
      owner's face followed an unfamiliar person's voice than in Congruent condition in
      which the owner's face followed the owner's voice. Generating a particular visual
      image in response to an unfamiliar voice should be difficult, and any expected
      images from the voice ought to be more obscure or less well defined than that of
      the owners. However, our subjects looked longer at the owner's face in
      Incongruent condition than in Congruent condition. This may indicate that dogs
      may have predicted that it should not be the owner when they heard the unfamiliar
      person's voice.

PMID- 16802146
TI  - Active attention modulates passive attention-related neural responses to sudden
      somatosensory input against a silent background.
AB  - To reveal whether active attention modulates neuronal responses related to
      passive attention to somatosensory stimuli presented suddenly against a silent
      background, we examined the passive attention-related change in amplitude of the
      event-related brain potentials (ERPs), caused by temporal infrequency of stimuli.
      Eighteen healthy subjects performed passive and active attention tasks in two
      stimulus conditions. In the oddball condition, frequent (80%, standard) and
      infrequent (20%, deviant) electrical stimuli were randomly delivered to the
      second and third digits of the left hand. In the deviant-alone condition, the
      deviant stimulus (deviant-alone stimulus) was delivered with the same timing and
      sequence as in the oddball condition without standard stimuli. The P100, N140,
      and P200 elicited by the deviant-alone stimulus were enhanced in amplitude
      compared to those evoked by the oddball deviant stimulus in both the active and
      passive tasks. Moreover, active attention increased the enhancement of P100 and
      N140. The difference waveform (deviant-alone minus oddball deviant) provided
      similar findings. In conclusion, active attention enhances neural responses
      related to passive shifts of attention to somatosensory signals suddenly
      presented against a silent background. The results indicate that top-down signals
      for detecting target stimuli interact with passive shifts of attention caused by
      bottom-up signals.

PMID- 16802147
TI  - Planning and online control of goal directed movements when the eyes are
      'relocated'.
AB  - We investigated the effects of different viewpoints on remapping visuo-motor
      space, and whether remapping happens differently during the planning and the
      online control phase of goal-directed movements. Participants tapped targets on a
      monitor that was placed horizontally flat and flush with the table in front of
      them. They viewed the layout of the scene, including the monitor, and their hand,
      through video goggles attached to a camera. The camera could be moved along a
      semi-circle with the monitor as the circle's center. On each trial, the camera
      was randomly positioned at one of seven locations on the semi-circle (-90 to +90
      degrees in 30 degrees steps), always at eye height. The time needed to tap the
      target was quickest when the camera was approximately facing the participant and
      progressively increased when the camera was located more to the sides (Experiment
      1). There was no effect of camera location on performance when participants only
      saw the static layout of the scene and were not allowed to see the scene or their
      hand during the movement (Experiment 2). By comparison, the dependency of
      performance on camera location increased when participants did not have
      information about the layout of the scene at the start of the trial, and could
      only perform remapping when their hand was visible during the movement
      (Experiment 3). These results indicate that visuo-motor remapping happens
      differently during the planning phase when only static information about the
      layout is available, and during the control phase when dynamic information about
      the moving hand is also available.

PMID- 16802148
TI  - CT analysis of the axis for transarticular screw fixation of rheumatoid
      atlantoaxial instability.
AB  - OBJECTIVE: To investigate the morphological characteristics of the axis of
      rheumatoid arthritis (RA) patients with atlantoaxial instability and to
      determine, by means of sagittal reconstructed computed tomography (CT), the
      suitability for atlantoaxial transarticular screw fixation. DESIGN AND PATIENTS:
      Twenty-seven patients, who had undergone reconstructed cervical spine CT scanning
      preoperatively and posterior atlantoaxial arthrodesis for atlantoaxial
      instability, were identified from a database for inclusion in this study. The
      isthmus height and internal height of the lateral mass of the axis were measured
      using digital imaging software. RESULTS: The mean isthmus height and internal
      height of the lateral mass of the axis in RA patients (n=14) were significantly
      lower than in non-RA patients (n=13) (P<0.01). A high-riding vertebral artery
      (VA) was present in 54% (15 joints, 9 patients) of the 28 atlantoaxial joints in
      the RA group and in 12% (3 joints, 2 patients) of the 26 atlantoaxial joints in
      the non-RA group (P<0.01). CONCLUSIONS: In RA patients, the axis showed more
      extensive thinning of the isthmus and lateral mass than in non-RA patients. A
      precise preoperative evaluation of screw trajectory using reconstruction CT
      imaging may be useful in atlantoaxial transarticular fixation, particularly for
      RA patients with atlantoaxial instability.

PMID- 16802149
TI  - Lack of in vivo mutagenicity and oxidative DNA damage by flumequine in the livers
      of gpt delta mice.
AB  - Flumequine (FLU), an anti-bacterial quinolone agent, has been recognized as a non
      genotoxic carcinogen for the mouse liver, but recent reports have suggested that
      some genotoxic mechanism involving oxidative DNA damage may be responsible for
      its hepatocarcinogenesis. In the present study, we investigated this possibility
      in the mouse liver using male and female B6C3F1 gpt delta mice fed diet
      containing 0.4% FLU, a carcinogenic dose, for 13 weeks. Measurements of 8
      hydroxydeoxyguanosine levels in liver DNA, and gpt point and deletion mutations
      revealed no significant increases in any of these parameters in either sex.
      Histopathologically, centrilobular swelling of hepatocytes with vacuolation was
      apparent, however, together with significant increase in bromodeoxyuridine
      labeling indices in the treated males and females. These results suggest that
      genotoxicity, including oxidative DNA damage, is not involved in mouse
      hepatocarcinogenesis by FLU, which might rather solely exert tumor-promoting
      effects in the liver.

PMID- 16802150
TI  - Current state and perspectives of truffle genetics and sustainable biotechnology.
AB  - Mycorrhizal fungi belonging to the genus Tuber produce, after the establishment
      of a productive interaction with a plant host, hypogeous fruitbodies of great
      economic value known as ''truffles''. This review summarizes the state of art on
      life cycle, genetic, and biotechnological investigations of Tuber spp. The
      ascocarp formation in truffles is a consequence of the activation of the sexual
      phase of the biological cycle. The formation of a dikaryotic secondary mycelium
      and the karyogamy in the ascal cell (followed by meiosis with ascospores
      formation) have been hypothesized by several authors but some doubts yet arise
      from the Tuber cycle by considering that a series of abnormalities have been
      pointed out in respect to other Ascomycetes. It is unclear if binucleated hyphal
      cells are derived from the fusion of mononucleated cells belonging to mycelia
      from different mating types or from one only. According to the karyotypes of
      Tuber melanosporum, Tuber magnatum, and Tuber borchii, the numbers of hyphal
      chromosomes suggest a chromosome number of eight (2n); these values are in the
      range of those of several Ascomycetes and observed for Tuber aestivum (2n=10).
      The importance and growth in interest during the last years in the fungi
      protoplasts isolation and transformation techniques can be related to current
      developments in Tuber genetics and biotechnology. T. borchii could be transformed
      through liposome-mediated delivery of genetic material as mycelial protoplasts
      isolation and fusion with liposomes has already been established. On the other
      hand, Agrobacterium-mediated transformation has been successfully established for
      T. borchii.

PMID- 16802151
TI  - Expression of gentisate 1,2-dioxygenase (gdoA) genes involved in aromatic
      degradation in two haloarchaeal genera.
AB  - Gentisate-1,2-dioxygenase genes (gdoA), with homology to a number of bacterial
      dioxygenases, and genes encoding a putative coenzyme A (CoA)-synthetase subunit
      (acdB) and a CoA-thioesterase (tieA) were identified in two haloarchaeal
      isolates. In Haloarcula sp. D1, gdoA was expressed during growth on 4
      hydroxybenzoate but not benzoate, and acdB and tieA were not expressed during
      growth on any of the aromatic substrates tested. In contrast, gdoA was expressed
      in Haloferax sp. D1227 during growth on benzoate, 3-hydroxybenzoate, cinnamate
      and phenylpropionate, and both acdB and tieA were expressed during growth on
      benzoate, cinnamate and phenylpropionate, but not on 3-hydroxybenzoate. This
      pattern of induction is consistent with these genes encoding steps in a CoA
      mediated benzoate pathway in this strain.

PMID- 16802152
TI  - Optimization of multienzyme production by two mixed strains in solid-state
      fermentation.
AB  - F(3) and F(4) strains of Aspergillus niger were screened from five strains of
      fungi to produce multienzyme preparations (containing cellulase, hemicellulase,
      glucoamylase, pectinase, and acidic proteinase) as dietary supplementation.
      Enzyme activities indicated that 1:4 (F(3) to F(4)) was the optimum mixture
      proportion, and 0.3% (W/W) was the preferable pitching rate. In bran mash
      containing 54.5% (W/W) water, F(3) and F(4) could produce the supplementation
      better when cultured 30 to 36 h at 30 degrees C. Monofactorial and orthogonal
      experiments were performed to optimize media. Results of the variance and range
      analysis showed that the optimum medium contained 80 g of bran, 20 g of
      cottonseed powder, 1 g of (NH(4))(2)SO(4), and 0.1 g of KH(2)PO(4). When F(3) and
      F(4 )strains were cultured in the optimum medium containing 54.5% (W/W) water,
      the activity of cellulase, hemicellulase, glucoamylase, pectinase, and acidic
      proteinase reached 996; 15,863; 13,378; 7,621; and 5,583 U/g, respectively.

PMID- 16802153
TI  - Tetramethylpyrazine production from glucose by a newly isolated Bacillus mutant.
AB  - 2,3,5,6-Tetramethylpyrazine (TTMP) was produced using a newly isolated Bacillus
      mutant. Culture medium optimization studies showed that soytone, an enzyme
      hydrolysate of soybean meal, with the supplementation of vitamins, can fully
      replace yeast extract plus peptone in supporting TTMP production from glucose. In
      a 5-l fermenter, using the optimized medium which contained 20% glucose, 5%
      soytone, 3% (NH(4))(2)HPO(4), and vitamin supplements, fermentations were carried
      out with stirring at 700 rpm, air flow at 1.0 vvm, controlled pH at 7.0, and
      temperature at 37 degrees C. TTMP reached 4.33 g l(-1) after 64.6 h cultivation.
      A product recovery method was described, which involved evaporation,
      crystallization, and lyophilization. The product purity was 99.88%, determined by
      GC with the normalization method. The main impurities were 2,3,5
      trimethylpyrazine (0.09%) and 2-ethyl-3,5,6-trimethylpyrazine (0.02%), which were
      identified by GC/MS. (13)C NMR determination also gave a consistent result.
      Natural and high purity of the product and the utilization of cheap green
      renewable materials make this process promising to compete with TTMP chemical
      synthetic methods.

PMID- 16802154
TI  - Enhanced productivity of protease-sensitive heterologous proteins by disruption
      of multiple protease genes in the fission yeast Schizosaccharomyces pombe.
AB  - The creation of protease-deficient mutants to avoid product degradation is one of
      the current strategies employed to improve productivity and secretion efficiency
      of heterologous protein expression. We previously constructed a set of single
      protease-deficient mutants of the fission yeast Schizosaccharomyces pombe by
      respective disruption of 52 protease genes, and we succeeded in confirming useful
      disruptants (Idiris et al., Yeast 23:83-99, 2006). In the present study, we
      attempted multiple deletions of 13 protease genes, single deletions of which were
      previously confirmed as being beneficial for reducing extracellular product
      degradation. Using PCR-based gene replacement, a series of multiple deletion
      strains was constructed by multiple disruption of a maximum of seven protease
      genes. Effects of the resultant multiple deletion strains on heterologous
      expression were then measured by practical expression of a proteolytically
      sensitive model protein, the human growth hormone (hGH). Time profiles of hGH
      secretion from each resultant mutant demonstrated significantly enhanced hGH
      productivity with processing of the multiple protease deletions. The data clearly
      indicated that disruption of multiple protease genes in the fission yeast is an
      effective method for controlling proteolytic degradation of heterologous proteins
      particularly susceptible to proteases.

PMID- 16802156
TI  - Towards on-line adaptation of neuro-prostheses with neuronal evaluation signals.
AB  - Many experiments have successfully demonstrated that prosthetic devices for
      restoring lost body functions can in principle be controlled by brain signals.
      However, stable long-term application of these devices, required for paralyzed
      patients, may suffer substantially from on-going signal changes for example
      adapting neural activities or movements of the electrodes recording brain
      activity. These changes currently require tedious re-learning procedures which
      are conducted and supervised under laboratory conditions, hampering the everyday
      use of such devices. As an efficient alternative to current methods we here
      propose an on-line adaptation scheme that exploits a hypothetical secondary
      signal source from brain regions reflecting the user's affective evaluation of
      the current neuro- prosthetic's performance. For demonstrating the feasibility of
      our idea, we simulate a typical prosthetic setup controlling a virtual robotic
      arm. Hereby we use the additional, hypothetical evaluation signal to adapt the
      decoding of the intended arm movement which is subjected to large non
      stationarities. Even with weak signals and high noise levels typically
      encountered in recording brain activities, our simulations show that prosthetic
      devices can be adapted successfully during everyday usage, requiring no special
      training procedures. Furthermore, the adaptation is shown to be stable against
      large changes in neural encoding and/or in the recording itself.

PMID- 16802155
TI  - PET/CT in patients with hepatocellular carcinoma using [(18)F]fluorocholine:
      preliminary comparison with [(18)F]FDG PET/CT.
AB  - PURPOSE: The diagnostic accuracy of [(18)F]fluorodeoxyglucose (FDG) PET is
      insufficient to characterise hepatocellular carcinoma (HCC) in liver masses and
      to diagnose all cases of recurrent HCC. HCC has been reported to take up
      [(11)C]acetate, but routine use of this tracer is difficult. Choline is another
      tracer of lipid metabolism, present in large amounts in HCC. In a proof-of
      concept study, we evaluated [(18)F]fluorocholine (FCH) uptake by HCC and compared
      FCH PET/CT with FDG PET/CT. METHODS: Twelve patients with newly diagnosed (n=8)
      or recurrent HCC (n=4) were prospectively enrolled. HCC was assessed by histology
      in eight cases and by American Association for the Study of Liver Diseases
      (AASLD) criteria in four cases. All patients underwent whole-body PET/CT 10 min
      after injection of 4 MBq/kg FCH. Within 1 week, 9 of the 12 patients also
      underwent whole-body FDG PET/CT 1 h after injection of 5 MBq/kg FDG. RESULTS: The
      per-patient analysis showed a detection rate of 12/12 using FCH PET/CT for both
      newly diagnosed and recurrent HCC. The median signal to noise ratio was 1.5+/
      0.38. There was a trend towards a higher FCH SUV(max) in well-differentiated HCC
      (15.6+/-7.9 vs 11.9+/-0.9, NS). Of the nine patients who underwent FCH and FDG
      PET/CT, all nine were positive with FCH whereas only five were positive with FDG.
      CONCLUSION: FCH provides a high detection rate for HCC, making it potentially
      useful in the initial evaluation of HCC or in the detection of recurrent disease.
      The favourable result of this proof-of-concept study opens the way to a phase III
      prospective study.

PMID- 16802157
TI  - Subcellular localization, expression patterns, SNPs and association analyses of
      the porcine HUMMLC2B gene.
AB  - Myosin regulatory light chain (MLC) regulates myofilament activation via
      phosphorylation by Ca(2+) dependant myosin light chain kinase. In order to
      further understand the functions of the porcine fast myosin regulatory light
      chain gene (HUMMLC2B) in muscle, the subcellular localization, the temporal and
      spatial distributions of its gene product were analyzed, and the association
      between the presence of specific polymorphisms and commercial meat traits in pig
      was also examined. HUMMLC2B was demonstrated to localize both in the cytoplasm
      and the nucleus by confocal fluorescence microscopy. Real-time PCR further
      revealed HUMMLC2B expression variation in a waveform manner in the skeletal
      muscle of both Chinese Tongcheng and Western Landrace pig breeds at days 33, 65
      and 90 post coitum (pc). After birth, the expression levels of HUMMLC2B were also
      found to decrease gradually with age. Our spatial expression analysis showed that
      HUMMLC2B was highly expressed in the semitendinosus, gastrocnemius, biceps
      femoris and longissimus dorsi muscles. In contrast, only low levels of expression
      of this gene were evident in fat, and no expression was detectable in brain,
      heart, kidney, lung, liver, lymph node, spleen, stomach, or in either large or
      small intestine. A total of 23 potential polymorphisms, comprising 3 exonic and
      20 intronic, were detectable in the porcine HUMMLC2B gene and the G1094A, T1513C,
      G1876A and T2005G polymorphisms were further analyzed. The significant
      associations between the T1513C, G1876A and T2005G polymorphisms with marbling
      score, dressing percent and meat color, respectively, were identified (P < 0.05).
      Associations with the percentage of leaf fat could also be demonstrated by
      analysis of haplotypes harboring these three polymorphisms. Our current results
      thus shed further light on the roles and functions of the HUMMLC2B gene in
      muscle.

PMID- 16802158
TI  - Wide mutational spectrum of a gene involved in hormone action and insecticide
      resistance in Drosophila melanogaster.
AB  - The Methoprene-tolerant (Met) bHLH-PAS gene in Drosophila melanogaster is
      involved in the molecular action of juvenile hormone (JH), and mutants result in
      resistance to the toxic and morphogenetic effects of JH and JH agonist
      insecticides such as methoprene. A detailed study of Met mutants can shed light
      on the poorly understood action of JH as well as the molecular basis of Met
      resistance to JH insecticides. Nine mutant alleles bearing point mutations in Met
      were examined for penetrance and expressivity of three phenotypic characters:
      resistance, defective oogenesis, and a novel eye defect. The collection ranged
      from two weak alleles having less severe phenotypes to strong alleles with severe
      phenotypes similar to that of a null allele. The point mutations were located in
      both conserved and nonconserved domains. Both the eye defect, seen as severely
      malformed ommatidial facets in the posterior margin of the compound eye, and the
      oogenesis phenotype are nonconditional, whereas expression of the resistance
      phenotype requires treatment with JH or JH analogs (JHAs) during early
      metamorphosis. A proposed basis for all the phenotypic characters centers on MET
      action as a transcriptional regulator of ecdysone secondary-response target genes
      during metamorphosis. Disruption of MET function either by mutation or by JHA
      presence during early metamorphosis results in transcriptional misregulation of
      different target genes, resulting in the pathology seen in either instance. The
      variety of amino acid changes in MET that resulted in resistance may portend a
      rapid rise in resistance in response to increased use of JH insecticides in field
      insect populations.

PMID- 16802159
TI  - The future of sleep medicine and the business of sleep.

PMID- 16802160
TI  - Mobilization and recovery of energy stores in traira, Hoplias malabaricus Bloch
      (Teleostei, Erythrinidae) during long-term starvation and after re-feeding.
AB  - In some neotropical environments, fishes often experience periods of poor food
      supply, especially due to extreme fluctuations in rainfall regime. The fish
      species that experience periods of drought such as the traira Hoplias malabaricus
      (Bloch 1794), may stand up to long-term food deprivation. In this study,
      experiments were performed in order to determine the dynamic of utilization of
      endogenous reserves in this species during starvation. Adult traira were both
      fasted for 30-240 days and re-fed for 30 days following 90 and 240 days of
      fasting. Glycogen and perivisceral fat were primary energy substrates consumed.
      During the first 30 days, fish consumed hepatic and muscular glycogen, without
      exhausting these reserves, and used lipids from perivisceral fat. Hepatic lipids
      were an important energy source during the first 60 days of starvation and
      perivisceral fat were consumed gradually, being exhausted after 180 days. Protein
      mobilization was noticeable after 60 days of fasting, and became the major energy
      source as the lipid reserves were decreased (between 90 and 180 days). Following
      the longest periods of food deprivation, fish had utilized hepatic glycogen
      again. Fish re-fed for 30 days after 90 and 240 days of fasting were able to
      recover hepatic glycogen stores, but not the other energy reserves.

PMID- 16802161
TI  - Timing and efficacy of transmitter release at mossy fiber synapses in the
      hippocampal network.
AB  - It is widely accepted that the hippocampus plays a major role in learning and
      memory. The mossy fiber synapse between granule cells in the dentate gyrus and
      pyramidal neurons in the CA3 region is a key component of the hippocampal
      trisynaptic circuit. Recent work, partially based on direct presynaptic patch
      clamp recordings from hippocampal mossy fiber boutons, sheds light on the
      mechanisms of synaptic transmission and plasticity at mossy fiber synapses. A
      high Na(+) channel density in mossy fiber boutons leads to a large amplitude of
      the presynaptic action potential. Together with the fast gating of presynaptic
      Ca(2+) channels, this generates a large and brief presynaptic Ca(2+) influx,
      which can trigger transmitter release with high efficiency and temporal
      precision. The large number of release sites, the large size of the releasable
      pool of vesicles, and the huge extent of presynaptic plasticity confer unique
      strength to this synapse, suggesting a large impact onto the CA3 pyramidal cell
      network under specific behavioral conditions. The characteristic properties of
      the hippocampal mossy fiber synapse may be important for pattern separation and
      information storage in the dentate gyrus-CA3 cell network.

PMID- 16802162
TI  - Quetiapine augmentation in treatment-resistant depression: a naturalistic study.
AB  - RATIONALE: Treatment-resistant depression (TRD) is a common clinical problem,
      often complicated with suicidal ideations and greater lifetime functional
      impairment, and represents a considerable challenge to management and treatment.
      OBJECTIVE: The aim of a prospective, open-label, noncomparative, flexible-dosed
      20-week study was to evaluate the effects of quetiapine, as an add-on therapy, in
      patients with TRD who were refractory to previous treatments. METHOD: Eighteen
      patients with major depressive disorder (DSM-IV criteria) were treated for 20
      weeks with quetiapine (mean dose 315+/-109 mg/day). Patients were evaluated at
      baseline, weekly from 1 to 9 weeks, and then after 12, 16, and 20 weeks of
      treatment, using Hamilton rating scale for depression-17 items (HAMD) scale.
      RESULTS: Fourteen patients with TRD completed the 20-week open trial with
      quetiapine. The augmentation with quetiapine significantly reduced total scores
      and scores listed in the anxiety subscale on the HAMD, and these effects were
      observed after the fourth week of treatment, while the depressed mood scores were
      significantly reduced after the fifth week of treatment. Quetiapine add-on
      treatment significantly decreased the scores listed in the insomnia subscale on
      the HAMD subscale after the second week of treatment. CONCLUSION: Our preliminary
      data indicate that quetiapine add-on therapy appears to have beneficial effects
      in the treatment of patients with TRD.

PMID- 16802163
TI  - Comparison of pramipexole and amisulpride on alertness, autonomic and endocrine
      functions in healthy volunteers.
AB  - RATIONALE: In a previous study in healthy volunteers, the anti-Parkinsonian drug
      pramipexole caused sedation and pupil dilatation, consistent with the stimulation
      of inhibitory D(2)/D(3) autoreceptors on the ventral tegmental area dopaminergic
      neurones. The sedation may be related to the removal of the dopaminergic
      excitation of the locus coeruleus (via the meso-coerulear pathway), whereas the
      pupil dilatation may be due to the removal of the dopaminergic excitation of the
      Edinger-Westphal nucleus (via a putative meso-pupillomotor pathway). OBJECTIVES:
      We investigated the hypothesis that amisulpride, a D(2)/D(3) receptor antagonist,
      would have effects opposite to those of pramipexole on alertness, pupillary and
      endocrine functions. MATERIALS AND METHODS: Pramipexole (0.5 mg), amisulpride (50
      mg), and their combination were administered to 16 healthy males in a balanced,
      cross-over, double-blind design. Tests included measures of alertness
      (Pupillographic Sleepiness Test, critical flicker fusion frequency, visual
      analogue scales), pupillary functions (resting pupil diameter, light and darkness
      reflex responses), non-pupillary autonomic functions (heart rate, blood pressure,
      salivation, core temperature), and endocrine functions [blood concentrations of
      prolactin, growth hormone (GH) and thyroid stimulating hormone (TSH)]. Data were
      analysed by ANOVA. RESULTS: Pramipexole reduced alertness and pupillary light
      reflex response amplitude, tended to reduce core temperature, reduced prolactin
      levels and increased GH levels. Amisulpride reduced pupil diameter, increased the
      amplitude of the light reflex response and prolactin and TSH levels. CONCLUSIONS:
      The opposite effects of pramipexole and amisulpride on alertness, pupillary
      function and pituitary hormone levels are consistent with their interactions with
      inhibitory D(2)/D(3) receptors on VTA neurones and in the tuberoinfundibular
      system.

PMID- 16802164
TI  - Atypical anxiolytic-like response to naloxone in benzodiazepine-resistant
      129S2/SvHsd mice: role of opioid receptor subtypes.
AB  - RATIONALE: Mice of many 129 substrains respond to environmental novelty with
      behavioural suppression and high levels of anxiety-like behaviour. Although
      resistant to conventional anxiolytics, this behavioural phenotype may involve
      stress-induced release of endogenous opioids. OBJECTIVES: To assess the effects
      of opioid receptor blockade on behavioural reactions to novelty stress in a
      chlordiazepoxide-resistant 129 substrain. MATERIALS AND METHODS: Experiment 1
      contrasted the effects of the broad-spectrum opioid receptor antagonist naloxone
      (1.0-10.0 mg/kg) in C57BL/6JOlaHsd and 129S2/SvHsd mice exposed to the elevated
      plus-maze. Experiments 2-4 examined the responses of 129S2/SvHsd mice to the mu
      selective opioid receptor antagonist beta-funaltrexamine (2.5-10.0 mg/kg), the
      delta-selective antagonist naltrindole (2.5-10.0 mg/kg) and the kappa-selective
      antagonist nor-binaltorphimine (2.5-5.0 mg/kg). RESULTS: 129 mice displayed
      higher levels of anxiety-like behaviour and lower levels of general exploration
      relative to their C57 counterparts. Although naloxone failed to alter the
      behaviour of C57 mice, both doses of this antagonist produced behaviourally
      selective reductions in open-arm avoidance in 129 mice. Surprisingly, none of the
      more selective opioid receptor antagonists replicated this effect of naloxone:
      beta-funaltrexamine was devoid of behavioural activity, naltrindole suppressed
      rearing (all doses) and increased immobility (10 mg/kg), while nor
      binaltorphimine (5 mg/kg) nonspecifically increased percent open arm entries.
      CONCLUSIONS: Recent evidence suggests differential involvement of opioid receptor
      subtypes in the anxiolytic efficacy of diverse compounds including conventional
      benzodiazepines. The insensitivity of 129 mice to the anxiolytic action of
      chlordiazepoxide, coupled with their atypical anxiolytic response to naloxone
      (but not more selective opioid receptor antagonists), suggests an abnormality in
      anxiety-related neurocircuitry involving opioid-GABA interactions.

PMID- 16802165
TI  - Use of tricyclic antidepressants in older patients with painful neuropathies.
AB  - OBJECTIVE: To describe patterns of use of tricyclic antidepressants (TCAs) (e.g.,
      amitriptyline, nortriptyline) in older patients with painful neuropathies.
      RESEARCH DESIGN AND METHODS: Using a large US health insurance claims database,
      we identified all persons who: (1) received a TCA between 1 January 1999 and 30
      June 2001, (2) were aged > or =65 years as of the date of their first
      prescription for a TCA during this period, and (3) had one or more health care
      encounters for the treatment of a painful neuropathy in the 30-day period
      immediately preceding their initial receipt of a TCA. We then examined the
      prevalence of selected comorbidities and/or concurrent use of medications that
      might render the prescribing of a TCA inappropriate, based on a listing of
      contraindications, warnings, and precautions found in the package inserts for
      these agents. Patterns of TCA use also were examined, based on information on
      paid claims. RESULTS: A total of 1,732 patients met all inclusion and exclusion
      criteria for the study. Their mean age was 74.6 years; 60.3% were women.
      Amitriptyline was the most frequently prescribed TCA (79.4% of patients). Forty
      one percent of study subjects receiving TCAs had conditions--primarily
      cardiovascular--that render the use of such agents potentially inappropriate. The
      mean daily dose of TCAs was universally low (about 23 mg). CONCLUSIONS: The high
      prevalence of conditions rendering the use of TCAs potentially inappropriate,
      along with relatively low daily dosages, suggest that many older patients with
      painful neuropathies who are prescribed these agents may be suboptimally treated.

PMID- 16802166
TI  - Effect of psychotropic medication on the in vitro metabolism of buprenorphine in
      human cDNA-expressed cytochrome P450 enzymes.
AB  - OBJECTIVE: The aim of the present study was to estimate the drug interaction
      potential of psychtropic medication on buprenorphine (BUP) N-dealkylation using
      cDNA-expressed cytochrome P450 (CYP) enzymes. METHODS: BUP was incubated with
      psychotropic drugs and cDNA-expressed CYP 3A4 and CYP 2C8 enzymes. Seven
      substances were screened for their inhibition potency. To check for a mechanism
      based component in inhibition, all substances were tested with and without
      preincubation, respectively. Norbuprenorphine (NBUP) concentrations were
      determined by liquid chromatography/tandem mass spectrometry, following
      liquid/liquid extraction. RESULTS: Midazolam and zolpidem demonstrated greatest
      inhibition in screening experiments. As expected, IC(50) values without
      preincubation were higher than those after 30-min preincubation, with zolpidem
      113.1 microM and midazolam 20.25 microM. Following a 30-min preincubation period
      in the absence of the probe substrate BUP, the apparent IC(50) values for
      zolpidem and midazolam were 20.17 microM and 3.5 microM. CONCLUSION: Both
      midazolam and zolpidem showed a distinct inhibitory potency towards NBUP
      formation by CYP 3A4, implicating a decreased conversion of BUP. When
      preincubated, the inhibitory potency was increased, which strongly suggests a
      metabolically activated component in inhibition.

PMID- 16802167
TI  - No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of
      the Alzheimer's disease brain.
AB  - Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R
      tau) and without (3R tau) exon 10, is believed to be a pathological consequence
      of certain tau mutations causing frontotemporal dementia. By assessing protein
      and mRNA levels of 4R tau and 3R tau in 27 AD and 20 control temporal cortex, we
      investigated whether altered tau splicing is a feature also in Alzheimer's
      disease (AD). However, apart from an expected increase of sarcosyl-insoluble tau
      in AD, there were no significant differences between the groups. Next, by laser
      capture microscopy and quantitative PCR, we separately analyzed CA1 hippocampal
      neurons with and without neurofibrillary pathology from six of the AD and seven
      of the control brains. No statistically significant differences in 4R tau/3R tau
      mRNA were found between the different subgroups. Moreover, we confirmed the
      absence of significant ratio differences in a second data set with laser-captured
      entorhinal cortex neurons from four AD and four control brains. Finally, the 4R
      tau/3R tau ratio in CA1 neurons was roughly half of the ratio in temporal cortex,
      indicating region-specific differences in tau mRNA splicing. In conclusion, this
      study indicated region-specific and possibly cell-type-specific tau splicing but
      did not lend any support to overt changes in alternative splicing of tau exon 10
      being an underlying factor in AD pathogenesis.

PMID- 16802168
TI  - High levels of diversity characterize mandrill (Mandrillus sphinx) Mhc-DRB
      sequences.
AB  - The major histocompatibility complex (MHC) is highly polymorphic in most primate
      species studied thus far. The rhesus macaque (Macaca mulatta) has been studied
      extensively and the Mhc-DRB region demonstrates variability similar to humans.
      The extent of MHC diversity is relatively unknown for other Old World monkeys
      (OWM), especially among genera other than Macaca. A molecular survey of the Mhc
      DRB region in mandrills (Mandrillus sphinx) revealed extensive variability,
      suggesting that other OWMs may also possess high levels of Mhc-DRB polymorphism.
      In the present study, 33 Mhc-DRB loci were identified from only 13 animals.
      Eleven were wild-born and presumed to be unrelated and two were captive-born
      twins. Two to seven different sequences were identified for each individual,
      suggesting that some mandrills may have as many as four Mhc-DRB loci on a single
      haplotype. From these sequences, representatives of at least six Mhc-DRB loci or
      lineages were identified. As observed in other primates, some new lineages may
      have arisen through the process of gene conversion. These findings indicate that
      mandrills have Mhc-DRB diversity not unlike rhesus macaques and humans.

PMID- 16802169
TI  - Inheritance and mapping of a powdery mildew resistance gene introgressed from
      Avena macrostachya in cultivated oat.
AB  - The powdery mildew resistance from Avena macrostachya was successfully
      introgressed into hexaploid oat (A. sativa). Genetic analysis of F(1), F(2), F(3)
      and BC(1) populations from two powdery-mildew resistant introgression lines
      revealed that the resistance is controlled by a dominant gene, tentatively
      designated Eg-5. Molecular marker analysis was conducted using bulked-segregant
      analysis in two segregating F(3) populations. One codominant simple sequence
      repeats (SSR) marker AM102 and four AFLP-derived PCR-based markers were
      successfully developed. The SSR marker AM102 and the STS marker ASE41M56 were
      linked to the gene Eg-5, with genetic distances of 2 and 0.4 cM, respectively, in
      both mapping populations. Three STS markers (ASE45M56, ASE41M61, ASE36M55) co
      segregated with Eg-5 in one population while two (ASE45M56, ASE36M55) of them
      linked to Eg-5 with a genetic distance of 1 cM in another population. The gene
      was further mapped to be in a region corresponding to linkage group 22_44+18 in
      the Kanota x Ogle (KO) hexaploid oat map by comparative mapping. To our
      knowledge, this is the first report of mapping powdery-mildew resistance in
      hexaploid oat. The new resistance source of A. macrostachya, together with the
      tightly linked markers identified here, could be beneficial in oat breeding
      programmes.

PMID- 16802170
TI  - Regression of white matter hypodensities with age in Aicardi-Goutieres syndrome:
      a case report.
AB  - BACKGROUND: Aicardi-Goutieres syndrome (AGS) is a severe and progressive familial
      encephalopathy that is characterized by acquired microcephaly, intracranial
      calcification, white matter lesions, and chronic lymphocytosis with elevated
      levels of interferon-alpha in the cerebrospinal fluid. Although the degree of
      calcification and the severity of brain atrophy are variable, typically, the
      brain lesions appear to progress on successive examinations. CASE REPORT: We
      report a 7-year-old male patient who showed relative regression of white matter
      lesions with nonprogression of basal ganglia calcification and atrophy on follow
      up magnetic resonance imaging and computed tomography scans. RESULTS: Magnetic
      resonance spectroscopy findings were normal. This, to our knowledge, is the first
      case report, which describes relative regression of the white matter changes in
      AGS.

PMID- 16802171
TI  - Novel thermostable single-stranded DNA-binding protein (SSB) from Deinococcus
      geothermalis.
AB  - To study the biochemical properties of single-stranded DNA-binding (SSB) protein
      from Deinococcus geothermalis (DgeSSB), we have cloned the ssb gene obtained by
      PCR and developed an overexpression system. The gene consists of an open reading
      frame of 900 nucleotides encoding a protein of 300 amino acids with a calculated
      molecular weight of 32.45 kDa. The amino acid sequence exhibits 43, 44 and 75%
      identity with Thermus aquaticus, Thermus thermophilus and Deinococcus radiodurans
      SSBs, respectively. We show that DgeSSB is similar to Thermus/Deinococcus SSB in
      its biochemical properties. DgeSSB includes two oligonucleotide/oligosaccharide
      binding folds per monomer and functions as a homodimer. In fluorescence
      titrations with poly(dT), DgeSSB bound about 30 nt independent of the salt
      concentration, and the fluorescence was quenched by about 65%. In a
      complementation assay in Escherichia coli, DgeSSB took over the in vivo function
      of EcoSSB. DgeSSB is thermostable with half-lives of 50 min at 70 degrees C and 5
      min at 90 degrees C. Hence, DgeSSB offers an attractive alternative for TaqSSB
      and TthSSB in their applications for molecular biology methods and for analytical
      purposes.

PMID- 16802172
TI  - Effects of N-starvation and C-source on Bradyrhizobium japonicum
      exopolysaccharide production and composition, and bacterial infectivity to
      soybean roots.
AB  - The exopolysaccharide (EPS) is an extracellular molecule that in Bradyrhizobium
      japonicum affects bacterial efficiency to nodulate soybean. Culture conditions
      such as N availability, type of C-source, or culture age can modify the amount
      and composition of EPS. To better understand the relationship among these
      conditions for EPS production, we analyzed their influence on EPS in B. japonicum
      USDA 110 and its derived mutant DeltaP22. This mutant has a deletion including
      the 3' region of exoP, exoT, and the 5' region of exoB, and produces a shorter
      EPS devoid of galactose. The studies were carried out in minimal media with the N
      source at starving or sufficient levels, and mannitol or malate as the only C
      source. Under N-starvation there was a net EPS accumulation, the levels being
      similar in the wild type and the mutant with malate as the C-source. By contrast,
      the amount of EPS diminished in N-sufficient conditions, being poyhydroxybutyrate
      accumulated with culture age. Hexoses composition was the same in both N
      situations, either with mannitol or malate as the only C-source, in contrast to
      previous observations made with different strains. This result suggests that the
      change in EPS composition in response to the environment is not general in B.
      japonicum. The wild type EPS composition was 1 glucose:0.5 galactose:0.5
      galacturonic acid:0.17 mannose. In DeltaP22 the EPS had no galactose but had
      galacturonic acid, thus indicating that it was not produced from oxidation of UDP
      galactose. Infectivity was lower in DeltaP22 than in USDA 110. When the mutant
      infectivity was compared between N-starved or N-sufficient cultures, the N
      starved were not less infective, despite the fact that the amounts of altered EPS
      produced by this mutant under N-starvation were higher than in N-sufficiency.
      Since this altered EPS does not bind soybean lectin, the interaction of EPS with
      this protein was not involved in increasing DeltaP22 infectivity under N
      starvation.

PMID- 16802173
TI  - Iron nutrition and physiological responses to iron stress in Nitrosomonas
      europaea.
AB  - Nitrosomonas europaea, as an ammonia-oxidizing bacterium, has a high Fe
      requirement and has 90 genes dedicated to Fe acquisition. Under Fe-limiting
      conditions (0.2 microM Fe), N. europaea was able to assimilate up to 70% of the
      available Fe in the medium even though it is unable to produce siderophores.
      Addition of exogenous siderophores to Fe-limited medium increased growth (final
      cell mass). Fe-limited cells had lower heme and cellular Fe contents, reduced
      membrane layers, and lower NH3- and NH2OH-dependent O2 consumption activities
      than Fe-replete cells. Fe acquisition-related proteins, such as a number of TonB
      dependent Fe-siderophore receptors for ferrichrome and enterobactin and diffusion
      protein OmpC, were expressed to higher levels under Fe limitation, providing
      biochemical evidence for adaptation of N. europaea to Fe-limited conditions.

PMID- 16802174
TI  - Growth substrate dependent localization of tetrachloroethene reductive
      dehalogenase in Sulfurospirillum multivorans.
AB  - Sulfurospirillum multivorans is a dehalorespiring organism, which is able to
      utilize tetrachloroethene as terminal electron acceptor in an anaerobic
      respiratory chain. The localization of the tetrachloroethene reductive
      dehalogenase in dependence on different growth substrates was studied using the
      freeze-fracture replica immunogold labeling technique. When the cells were grown
      with pyruvate plus fumarate, a major part of the enzyme was either localized in
      the cytoplasm or membrane associated facing the cytoplasm. In cells grown on
      pyruvate or formate as electron donors and tetrachloroethene as electron
      acceptor, most of the enzyme was detected at the periplasmic side of the
      cytoplasmic membrane. These results were confirmed by immunoblots of the enzyme
      with and without the twin arginine leader peptide. Trichloroethene exhibited the
      same effect on the enzyme localization as tetrachloroethene. The data indicated
      that the localization of the enzyme was dependent on the electron acceptor
      utilized.

PMID- 16802175
TI  - Phylogeny of nodulation genes and symbiotic properties of Genista tinctoria
      bradyrhizobia.
AB  - Pairwise comparisons of Genista tinctoria (dyer's weed) rhizobium nodA, nodC, and
      nodZ gene sequences to those available in databanks revealed their highest
      sequence identities to nodulation loci of Bradyrhizobium sp. (Lupinus) strains
      and rhizobia from other genistoid legumes. On phylogenetic trees, genistoid
      microsymbionts were grouped together in monophyletic clusters, which suggested
      that their nodulation genes evolved from a common ancestor. G. tinctoria
      nodulators formed symbioses not only with the native host, but also with other
      plants of Genisteae tribe such as: Lupinus luteus, Sarothamnus scoparius, and
      Chamaecytisus ratisbonensis, and they were classified as the genistoid cross
      inoculation group. The dyer's weed root nodules were designated as indeterminate
      with apical meristem consisting of infected and uninfected cells.

PMID- 16802176
TI  - N-acetyltaurine dissimilated via taurine by Delftia acidovorans NAT.
AB  - The naturally occurring sulfonate N-acetyltaurine was synthesized chemically and
      its identity was confirmed. Aerobic enrichment cultures for bacteria able to
      utilize N-acetyltaurine as sole source of fixed nitrogen or as sole source of
      carbon were successful. One representative isolate, strain NAT, which was
      identified as a strain of Delftia acidovorans, grew with N-acetyltaurine as
      carbon source and excreted stoichiometric amounts of sulfate and ammonium.
      Inducible enzyme activities were measured in crude extracts of this organism to
      elucidate the degradative pathway. Cleavage of N-acetyltaurine by a highly active
      amidase yielded acetate and taurine. The latter was oxidatively deaminated by
      taurine dehydrogenase to ammonium and sulfoacetaldehyde. This key intermediate of
      sulfonate catabolism was desulfonated by the known reaction of sulfoacetaldehyde
      acetyltransferase to sulfite and acetyl phosphate, which was further degraded to
      enter central metabolism. A degradative pathway including transport functions is
      proposed.

PMID- 16802177
TI  - Organ specific analysis of the anaerobic primary metabolism in rice and wheat
      seedlings II: light exposure reduces needs for fermentation and extends survival
      during anaerobiosis.
AB  - Low oxygen stress in plants can occur during flooding and compromise the
      availability and utilization of carbohydrates in root and shoot tissues. Low
      oxygen-tolerant rice and -sensitive wheat plants were analyzed under anaerobiosis
      in light to evaluate main factors of the primary metabolism that affect
      sensitivity against oxygen deprivation: activity of glycolysis and the rate of
      photosynthesis. Relatively stable ATP contents (93 and 58% of aerated control
      levels after 24 h anaerobiosis) in illuminated shoot tissues account for enhanced
      tolerance of rice and wheat seedlings to anaerobiosis upon light exposure in
      comparison to anoxia in darkness. Although the photosynthetic process was
      inhibited during low oxygen stress, which was partly due to CO(2) deficiency,
      more light-exposed than dark-incubated seedlings survived. Illuminated plants
      could tolerate a 70% lower anaerobic ethanol production in shoots in comparison
      to darkness, although still an 18-times higher ethanol production rate was
      determined in rice than in wheat leaves. In conclusion, light-exposed plants
      grown under anaerobiosis may recycle low amounts of generated oxygen between
      photosynthesis and dissimilation and generate additional energy not only from
      substrate phosphorylation during glycolysis but also from other sources like
      cyclic electron transport.

PMID- 16802178
TI  - Candesartan cilexetil in children with hypertension or proteinuria: preliminary
      data.
AB  - The angiotensin II receptor blockers irbesartan and losartan effectively reduce
      blood pressure and proteinuria in childhood. We were impressed by the neutral
      taste and the small size of the candesartan cilexetil tablets. This angiotensin
      II receptor blocker was used during 4 months in 17 pediatric patients (aged 0.5
      16, median 4.5 years) with chronic arterial hypertension (n=6), overt proteinuria
      (n=2), or both (n=9). The initial candesartan dose of 0.23 (0.16-0.28) mg/kg body
      weight once daily (median and interquartile ranged) was doubled in ten patients
      [final dose 0.35 (0.22-0.47) mg/kg body weight]. No adverse clinical experiences
      were noted on candesartan. Candesartan increased plasma potassium by 0.3 (0.0
      0.8) mmol/l (P<0.01). In children with arterial hypertension, blood pressure
      decreased by 9 (3-13)/9 (3-18) mmHg (P<0.01); in those with overt proteinuria the
      urinary albumin/creatinine ratio decreased by 279 (33-652) mg/mmol (P<0.05). In
      conclusion, in children candesartan reduces blood pressure and proteinuria with
      an excellent short-term tolerability profile.

PMID- 16802179
TI  - Pilot survey of subway and bus stop noise levels.
AB  - Excessive noise exposure is a serious global urban health problem, adversely
      affecting millions of people. One often cited source of urban noise is mass
      transit, particularly subway systems. As a first step in determining risk within
      this context, we recently conducted an environmental survey of noise levels of
      the New York City transit system. Over 90 noise measurements were made using a
      sound level meter. Average and maximum noise levels were measured on subway
      platforms, and maximum levels were measured inside subway cars and at several bus
      stops for comparison purposes. The average noise level measured on the subway
      platforms was 86 +/- 4 dBA (decibel-A weighting). Maximum levels of 106, 112, and
      89 dBA were measured on subway platforms, inside subway cars, and at bus stops,
      respectively. These results indicate that noise levels in subway and bus stop
      environments have the potential to exceed recommended exposure guidelines from
      the World Health Organization (WHO) and U.S. Environmental Protection Agency
      (EPA), given sufficient exposure duration. Risk reduction strategies following
      the standard hierarchy of control measures should be applied, where feasible, to
      reduce subway noise exposure.

PMID- 16802180
TI  - Power and action in critical theory across disciplines: implications for critical
      community psychology.
AB  - Although critical scholarship and community psychology share similar aspirations,
      the links between them remain unexplored and under-theorized. In this article we
      explore the implications of critical scholarship in various specialties for the
      field of community psychology. To understand the contributions of critical
      scholarship to a theory of power and action for social change, we conducted a
      systematic analysis of a ten-year period of publications in seven journals
      associated with the critical scholarship tradition. We created precise criteria
      for the concepts of power and action and applied them to the publications.
      Results indicate an interesting paradox at play. Whereas community psychology is
      more action oriented than critical scholarship, its actions fall short of
      challenging institutionalized power structures and the status quo; and whereas
      critical scholarship is more challenging of the status quo than community
      psychology in theory, it has failed to produce viable actions that challenge the
      status quo. We discuss the implications of this state of affairs for the
      development of a more critical community psychology.

PMID- 16802181
TI  - External, not internal challenges to interdisciplinary research.
AB  - This commentary draws on personal experience with interdisciplinary
      collaborations to suggest that Maton, Perkins, and Saegert (this issue) may
      overstate the challenges internal to interdisciplinary work groups. It supports
      their discussion of external challenges, and comments on the efforts they suggest
      to further interdisciplinary work.

PMID- 16802182
TI  - Two monozygotic twin pairs discordant for female-to-male transsexualism.
AB  - Two monozygotic female twin pairs discordant for transsexualism are described.
      These reports double the number of such case studies in the current scientific
      literature. Interviews with the twins and their families indicated that unusual
      medical and life history factors did not play causal roles. However, inspection
      of medical records for one transsexual twin suggested that some early life
      experiences may have exacerbated tendencies toward male gender identification. In
      both pairs, the twins' gender identity differences emerged early, consistent
      with, but not proof of, co-twin differences in prenatal hormonal influences. The
      identification of additional discordant MZ female twin pairs can advance
      biological and psychological understanding of transsexualism. Suggestions for
      future research, based upon findings from these two twin pairs and from studies
      of female-to-male transsexuals, are provided.

PMID- 16802183
TI  - Pubertal onset and sexual orientation in an adolescent national probability
      sample.
AB  - Using 6-year longitudinal data from the National Longitudinal Survey of
      Adolescent Health (Add Health) and multiple measures of puberty as it occurs and
      of sexual orientation (romantic attraction, sexual identity), the present study
      attempted to replicate previous research which reported that homosexuals and
      heterosexuals differed in their age of pubertal onset. The study hypotheses were
      not confirmed for either males or females: on most pubertal measures, same-sex
      oriented groupings did not differ from heterosexuals. The only significant
      findings regarding homosexual males indicated that they were more likely to
      report having a later rather than an earlier onset of puberty, and the
      significant findings regarding homosexual females were contradictory--they tended
      to have an earlier onset of puberty. These findings are attributed to
      methodological improvements in the present study that reduced retrospective bias,
      used multiple indicators of sexual orientation and puberty timing, and assessed
      less eroticized measures of puberty.

PMID- 16802184
TI  - Keyboard use and musculoskeletal outcomes among computer users.
AB  - BACKGROUND: In this review, the epidemiological evidence examining associations
      between upper extremity musculoskeletal symptoms and disorders and keyboard use
      intensity (hours of computer use-per day or per-week) and computer user posture
      was explored. METHODS: An OVID Medline literature search was conducted to
      identify papers published in the peer-reviewed medical literature between 1966
      and November, 2005. A total of 558 citations were found and reviewed. Those
      papers in which associations between musculoskeletal outcomes and (1) posture
      (ascertained by a study investigator) or (2) computer use, in units of hours-per
      day, hours-per-week, or as a percent of work-time, were included in the review.
      RESULTS: Thirty-nine epidemiological studies examining associations between
      computer use and MSD outcomes were identified. While the observational
      epidemiological literature was heterogeneous, some trends did emerge. It appears
      that the most consistent finding was the association observed between hours
      keying and hand/arm outcomes. Associations between some postural effects and
      musculoskeletal outcomes may also be inferred from the literature. In particular,
      placing the keyboard below the elbow, limiting head rotation, and resting the
      arms appears to result in reduced risk of neck/shoulder outcomes. Minimizing
      ulnar deviation and keyboard thickness appears to result in reduced risk of
      hand/arm outcomes. CONCLUSIONS: Several methodological limitations, including non
      representative samples, imprecise or biased measures of exposure and health
      outcome, incomplete control of confounding, and reversal of cause and effect, may
      contribute to the heterogeneity of observed results. Suggestions are made for
      improving the validity of future investigations.

PMID- 16802185
TI  - Secondary prevention of work-related upper extremity disorders: recommendations
      from the Annapolis conference.
AB  - INTRODUCTION: Efforts to improve the secondary prevention of work-related upper
      extremity (WRUE) symptoms continue to present a challenge. As with many
      occupational musculoskeletal pain disorders no single, direct cause-effect
      relationship exists among specific exposures, pathologic processes, and symptoms.
      The field has yet to create truly effective and efficient interventions for these
      problems that are based on current epidemiological and clinical knowledge.
      METHODS: A working conference was held in Annapolis, Maryland on September 23rd
      and 24th, 2005 with leaders in research and application related to upper
      extremity disorders to address this challenge. The intent of the meeting was to
      review "state of the art" evidence in epidemiology and intervention research in
      order to develop suggestions regarding next steps in intervention research and
      application. On day 2 a number of stakeholders were present to discuss what they
      perceived as the missing pieces in both epidemiological research and applied
      intervention research in order to generate more effective workplace
      interventions. RESULTS: The papers in this series of the Journal of Occupational
      Rehabilitation indicate that scientifically sound progress has been made over the
      past decade in identifying ergonomic, workplace psychosocial, and individual
      factors in both the etiology and exacerbation of these symptoms/disorders.
      However, there is a gap between this knowledge and the development and practical
      implementation of comprehensive interventions for these problems. The conference
      also highlighted the paucity of economic analyses of the impact of these
      disorders as well as the economic study of the impact of intervention. Approaches
      for such evaluations were presented and are included in this special section of
      the journal. CONCLUSIONS: This series of papers and the summary of the invited
      group's discussions provided in this paper clearly emphasize the need for
      innovative ways to think about these problems and specific research topics that
      can help translate this knowledge into effective secondary prevention efforts.

PMID- 16802186
TI  - Preconception care and treatment with assisted reproductive technologies.
AB  - Couples with fertility problems seeking treatment with assisted reproductive
      technologies (ART) such as in vitro fertilization should receive preconception
      counseling on all factors that are provided when counseling patients without
      fertility problems. Additional counseling should address success rates and
      possible risks from ART therapies. Success rates from ART are improving, with the
      highest live birth rates averaging about 40% per cycle among women less than 35
      years old. A woman's age lowers the chance of achieving a live birth, as do
      smoking, obesity, and infertility diagnoses such as hydrosalpinx, uterine
      leiomyoma, or male factor infertility. Singletons conceived with ART may have
      lower birth weights. Animal studies suggest that genetic imprinting disorders may
      be induced by certain embryo culture conditions. The major risk from ovarian
      stimulation is multiple gestation. About one-third of live-birth deliveries from
      ART have more than one infant, and twins represent 85% of these multiple-birth
      children. There are more complications in multiple gestation pregnancies, infants
      are more likely to be born preterm and with other health problems, and families
      caring for multiples experience more stress. Transferring fewer embryos per cycle
      reduces the multiple birth rate from ART, but the patient may have to pay for
      additional cycles of ART because of a lower likelihood of pregnancy.

PMID- 16802187
TI  - Modifiable risk factors for low birth weight and their effect on cerebral palsy
      and mental retardation.
AB  - OBJECTIVE: to estimate the effect of modifiable risk factors on low birth weight
      and two of its sequelae-cerebral palsy and mental retardation. METHODS: The
      population attributable risk percent (PARP) was used as a measure of effect. A
      literature search was conducted to determine estimates of the percent of CP and
      MR attributable to low birth weight. Data from the 1996-1997 Georgia Pregnancy
      Risk Assessment Monitoring System (PRAMS), a population based surveillance
      system, were used to estimate the percent of low birth weight attributable to
      modifiable risk factors. The PARP was calculated for smoking and unwanted
      conception. RESULTS: Unwanted pregnancy and smoking were statistically
      significant risk factors for LBW. Four percent of all LBW births were
      attributable to unwanted pregnancy. If all unwanted pregnancies were prevented,
      13% of cases of CP (27 cases per year in GA) and 14% of cases of MR (151 cases
      per year in GA) would be prevented. In wanted or mistimed pregnancies, 6% of LBW
      births were attributable to smoking. If all smoking during wanted or mistimed
      pregnancy was prevented, an additional 2.5% (5 cases) of CP and an additional
      0.8% (8 cases) of MR would be prevented in Georgia each year. If all unwanted
      pregnancies and all smoking during wanted or mistimed pregnancies were prevented,
      1692 LBW births could be prevented per year and the rate of LBW in Georgia would
      fall from 7.6% to 6.8%. Additionally, 32 cases of cerebral palsy and 159 cases of
      mental retardation could be prevented each year in Georgia. CONCLUSIONS: The PARP
      approach is useful in estimating the benefit of evidence-based prevention
      services. Preventing unwanted pregnancy and smoking during pregnancy would
      substantially reduce the burden of cerebral palsy and mental retardation in
      Georgia.

PMID- 16802188
TI  - Public finance policy strategies to increase access to preconception care.
AB  - Policy and finance barriers reduce access to preconception care and, reportedly,
      limit professional practice changes that would improve the availability of needed
      services. Millions of women of childbearing age (15-44) lack adequate health
      coverage (i.e., uninsured or underinsured), and others live in medically
      underserved areas. Service delivery fragmentation and lack of professional
      guidelines are additional barriers. This paper reviews barriers and opportunities
      for financing preconception care, based on a review and analysis of state and
      federal policies. We describe states' experiences with and opportunities to
      improve health coverage, through public programs such as Medicaid, Medicaid
      waivers, and the State Children's Health Insurance Program (SCHIP). The potential
      role of Title V and of community health centers in providing primary and
      preventive care to women also is discussed. In these and other public health and
      health coverage programs, opportunities exist to finance preconception care for
      low-income women. Three major policy directions are discussed. To increase access
      to preconception care among women of childbearing age, the federal and state
      governments have opportunities to: (1) improve health care coverage, (2) increase
      the supply of publicly subsidized health clinics, and (3) direct delivery of
      preconception screening and interventions in the context of public health
      programs.

PMID- 16802189
TI  - Prevalence and correlates of pregnancy loss history in a national sample of
      children and families.
AB  - Public health prevalence data has consistently illustrated disparities in fetal
      mortality prevalence on a yearly basis, yet few studies have examined the
      prevalence and correlates of pregnancy loss history during the reproductive life
      span. Using nationally representative data from the Early Childhood Longitudinal
      Study, Birth Cohort, approximately 25% of childbearing women in the United States
      were found to have experienced one or more fetal deaths prior to the current live
      birth. An examination of the demographic correlates of singular and multiple loss
      history in age-controlled models reveals that a history of multiple loss was
      significantly related to African-American race, lower socioeconomic status,
      income below poverty, and lower maternal education. Singular loss history risk
      was relatively consistent across social and demographic groups with some
      increased risk noted only for African-American women. Predictive correlates of
      fetal mortality varied by racial-ethnic subpopulation in multivariate analysis.
      Findings from this study are discussed for their contribution to existing public
      health knowledge and the potential for future research focused on the experience
      of multiple loss and demographic groups at elevated risk.

PMID- 16802190
TI  - A comparison of maternal interview and medical record ascertainment of violence
      among women who had poor pregnancy outcomes.
AB  - OBJECTIVES: This study investigated the agreement between self-reported and
      medical record assessment of exposure to violence and the impact of
      misclassification on the estimation of the association between exposure to
      violence and infant death and very low birthweight. METHODS: The study population
      consisted of women who participated in two case-control studies on infant death
      and very low birthweight. There were 254 pairs of interviews and medical record
      reviews available for comparison. RESULTS: A total of 153 women (60.2%) reported
      ever being exposed to violence--92 (60.1%) based on the interview only, 18
      (11.8%) based on the medical record only, and 43 (28.1%) in both sources. The
      sensitivity of the violence variables was low, ranging from 16.9% to 31.9% and
      kappa statistics showed poor agreement. Lower rates of all types of violence were
      found through the medical record than through the interview. CONCLUSION:
      Prevalence of violence based on medical record alone had a high degree of
      misclassification and some odds ratios were biased toward the null. Studies in
      which violence is an exposure, outcome, or confounder must use participant
      interviews in order to gather accurate information. A combination of sources may
      be the most accurate.

PMID- 16802191
TI  - Endogenous signaling complexity in neuropeptides- leucine- and methionine
      enkephalin.
AB  - 1. In addition to his many fine contributions in furthering our understanding of
      the neurochemical action of ecosanoids, catchelomines, steroids, anandamines,
      cannabinoids, endorphins, and the many modifications made to these neural
      factors, twenty years ago Julius Axelrod published a noteworthy paper concerning
      the nature of neuropeptides and their potential for multiple neurophysiological
      effects (Redgate et al., 1986). 2. In that report, Axelrod and coworkers
      described the neurological actions of the then recently discovered leucine- and
      methionine-enkephalins, and their biological functions which were novel,
      atypical, and in possession of neurological effects that were significantly "much
      more than additive." 3. In this short communication I would like to expand on
      this observation concerning the "additive effects" contained within the amino
      acid sequence of the atypical neurotransmitter peptides leucine- and methonine
      enkephalin.

PMID- 16802192
TI  - Hyperthermia-induced seizures modify the GABA(A) and benzodiazepine receptor
      binding in immature rat brain.
AB  - Effects of hyperthermia-induced seizures (HS) on GABA(A) and benzodiazepine (BDZ)
      receptor binding in immature rat brain were evaluated using in vitro
      autoradiography. HS were induced in 10-days-old rats by a regulated stream of
      moderately heated air directed 50 cm above the animals. Rats were killed 30 min,
      24 h or 20 days after HS and their brains were used for in vitro autoradiography
      experiments to determine GABA(A) and BDZ receptor binding. GABA(A) binding was
      significantly enhanced in all brain areas evaluated 30 min after HS, an effect
      that endures 24 h and 20 days after seizures. Concerning BDZ receptor binding, a
      significant increase was detected in entorhinal and perirhinal cortices and
      decreased in basolateral amygdala 30 min following HS. One day after HS, animals
      demonstrated enhanced BDZ binding in the cingulate, frontal, posterior parietal,
      entorhinal, temporal and perirhinal cortices; striatum, accumbens, substantia
      nigra pars compacta and amygdala nuclei. Twenty days after HS enhanced BDZ
      binding was restricted in the cingulated, frontal, anterior and posterior
      parietal cortices, as well as in substantia nigra pars reticulata, whereas
      decreased values were found in accumbens nucleus and substantia nigra pars
      compacta. Our data indicate differential effects of HS in GABA(A) and BDZ binding
      in immature brain. HS-induced GABA(A) and BDZ changes are different from those
      previously described in experimental models of temporal lobe epilepsy in adult
      animals.

PMID- 16802193
TI  - Obituary--Evgenia Davydovna Homskaya.

PMID- 16802194
TI  - Change trajectories in women's STD/HIV risk behaviors following intervention.
AB  - Three 16-month sexual risk-taking trajectories were identified in 287 women in an
      STD/HIV intervention study. The Risk Eliminator group reported no sex risk
      following intervention while the Risk Reducer group reported continuous drops
      over time. The High Risk group reported higher initial risk than the other two
      and no subsequent changes. The trajectory groups showed no between- or within
      group effects of intervention exposure. Trajectory groups were compared on
      baseline characteristics. No differences were seen in demographics or STD/HIV
      knowledge. Compared to one or both of the other groups, the High Risk women
      reported more lifetime partners, recent paying partners, adult rape, and recent
      substance use. Their steady partners were more likely to be abusive, intoxicated
      during sex (as were the women themselves), and believed to be non-monogamous. The
      Risk Eliminator group differed from the other two by being less likely to report
      a history of childhood sexual abuse.

PMID- 16802195
TI  - Depression and CD4 cell count among persons with HIV infection in Uganda.
AB  - Despite the importance of mental illness and the high prevalence of HIV in
      Africa, few studies have documented depressive symptoms among HIV-infected
      persons in Africa. We assessed factors associated with depression among HIV
      infected adults undergoing anti-retroviral eligibility screening in Eastern
      Uganda. Depressive symptoms were measured using the Center for Epidemiologic
      Studies Depression Scale (CES-D). Univariate and multiple regression analyses
      were conducted to identify socio-demographic characteristics and disease-related
      factors associated with depression. Among 1017 HIV-infected participants assessed
      for depression, 47% (476/1017) reported depressive symptoms (CES-D >/= 23).
      Adjusting for age, gender, education, and source of income, patients with CD4
      counts <50 cells/microl were more likely to be depressed (odds ratio 2.34, 95%
      confidence interval, 1.39-3.93, P = 0.001). Women, participants >50 years, and
      those without an income source were more likely to be depressed. Depression was
      common among HIV-infected persons in rural Uganda and was associated with low CD4
      cell counts. Appropriate screening and treatment for depression should be
      considered for comprehensive HIV care.

PMID- 16802196
TI  - Liquid courage: alcohol fosters risky sexual decision-making in individuals with
      sexual fears.
AB  - The interaction of sexual fear and acute alcohol intoxication on the likelihood
      of risky sexual behavior was explored. Participants (Ps; N = 115) completed a
      measure of sexual fears and were randomly assigned to no-, low-, or high-dose
      alcohol conditions. Ps then read an eroticized vignette, where they were the
      protagonist, and rated their likelihood of sex with a new partner when no condom
      was available. Controlling for gender and social desirability, compared to sober
      Ps, highly intoxicated Ps indicated that they were more likely to engage in risky
      sexual behaviors. Sexual fear was modestly negatively related to risky sex
      likelihood among sober or mildly intoxicated Ps but strongly positively related
      to risky sex likelihood among highly intoxicated Ps. Findings underscore the
      notion that alcohol affects different types of individuals differently and
      indicate that alcohol may foster sexual risk-taking, in part, by attenuating or
      counteracting fear or anxiety.

PMID- 16802197
TI  - Potential bridges for HIV infection to men who have sex with men in Guangzhou,
      China.
AB  - To assess the potential for HIV acquisition among men who have sex with men (MSM)
      in Guangzhou, China, we conducted a cross-sectional, anonymous, face-to-face
      survey of MSM in the metropolitan area of Guangzhou, China. As a pilot
      recruitment for a cohort study, participants were recruited by convenience
      sampling through newspaper and television advertising, website information, and
      respondent referral. Blood samples were tested for HIV, hepatitis B (HBV),
      hepatitis C (HCV), and syphilis. Client-centered HIV and STD counseling was
      provided.A total of 201 MSM were interviewed and 200 blood samples were tested.
      The prevalence of HIV antibody was 0% (97.5% CI 0-1.8%); 17.5% of MSM were HBV
      surface antigen positive; 1.0% had HCV antibodies; 10.5% had antibodies to
      syphilis. Syphilis seropositivity was associated with sex with a foreign MSM in
      the last six months and 10.4% reported sex with a foreign MSM overall. The
      majority (54.7%) reported unprotected anal sex with other men. Nearly one-third
      (31.8%) had regular female partners; 25.9% were currently married to a woman; 6%
      had casual female partners; 4.5% had sex with a female sex worker; 4.5% had sex
      with a male sex worker; and 12.9% had unprotected vaginal sex and unprotected
      anal sex with a man in the past six months. Only one MSM reported injection drug
      use (0.5%). The currently low prevalence of HIV but high level of unprotected
      anal sex, high prevalence of syphilis infection, and sexual networks that include
      foreign MSM point to a transient window for HIV prevention among MSM in
      Guangzhou. We recognize challenges to recruiting a representative sample of MSM
      and retaining them in longitudinal cohort studies.

PMID- 16802198
TI  - Hematospermia: imaging findings.
AB  - Hematospermia is an anxiety provoking but otherwise generally benign and self
      limited condition that is infrequently associated with significant underlying
      pathology, and is most often considered to be idiopathic in nature. Management
      with routine clinical evaluation, watchful waiting, and reassurance generally
      suffice without further diagnostic workup or treatment. Noninvasive imaging may
      play an important role in the diagnostic workup of men with hematospermia,
      particularly in those who are >40 years old, have other associated symptoms or
      signs of disease, or have persistence of hematospermia. Many entities may be
      encountered in association with hematospermia at imaging, and specific
      therapeutic interventions may be used if certain treatable underlying pathologies
      are coincidentally detected. In this comprehensive review, we discuss the
      potential etiologies, diagnostic workup, imaging techniques, relevant male pelvic
      anatomy, imaging appearance of specific associated pathologies, and treatment for
      hematospermia.

PMID- 16802199
TI  - A new 3-D diagnosis strategy for duodenal malignant lesions using multidetector
      row CT, CT virtual duodenoscopy, duodenography, and 3-D multicholangiography.
AB  - Recent advances in multidetector row computed tomography (MD-CT) technology
      provide new opportunities for clinical diagnoses of various diseases. Here we
      assessed CT virtual duodenoscopy, duodenography, and three-dimensional (3D)
      multicholangiography created by MD-CT for clinical diagnosis of duodenal
      malignant lesions. The study involved seven cases of periduodenal carcinoma (four
      ampullary carcinomas, two duodenal carcinomas, one pancreatic carcinoma). Biliary
      contrast medium was administered intravenously, followed by intravenous
      administration of an anticholinergic agent and oral administration of
      effervescent granules for expanding the upper gastrointestinal tract. Following
      intravenous administration of a nonionic contrast medium, an upper abdominal MD
      CT scan was performed in the left lateral position. Scan data were processed on a
      workstation to create CT virtual duodenoscopy, duodenography, 3D
      multicholangiography, and various postprocessing images, which were then
      evaluated for their effectiveness as preoperative diagnostic tools. Carcinoma
      location and extent were clearly demonstrated as defects or colored low-density
      areas in 3-D multicholangiography images and as protruding lesions in virtual
      duodenography and duodenoscopy images. These findings were confirmed using
      multiplanar or curved planar reformation images. In conclusion, CT virtual
      duodenoscopy, doudenography, 3-D multicholangiography, and various images created
      by MD-CT alone provided necessary and adequate preoperative diagnostic
      information.

PMID- 16802200
TI  - Role of percutaneous transhepatic obliteration for special types of varices with
      portal hypertension.
AB  - The treatment of special types of varices with portal hypertension has not yet
      been established. We were able to control 13 cases of special types of varices by
      percutaneous transhepatic obliteration (PTO). These 13 cases consisted of 2
      esophagojejunal varices after total gastrectomy for gastric cancer, 1 stoma
      varices after abdominoperineal excision for rectal cancer, 2 mesenteric varices
      with encephalopathy, 1 gastric variceal rupture, 1 gastrorenal and gastroazygos
      shunt with encephalopathy, 3 giant bar-type esophageal varices, 2 isolated
      gastric varices with gastropericardiac shunts, and 1 isolated gastric varices
      with gastrophrenic shunt. The special types of varices were successfully
      embolized in all cases and there were no complications. We conclude that the PTO
      is still an effective and safe treatment for special types of varices with portal
      hypertension.

PMID- 16802201
TI  - Focal liver lesions: sinusoidal phase of CEUS.
AB  - Ultrasound examination is the first imaging modality for hepatic study in
      neoplastic and chronic liver diseases. Focal liver lesions frequently cause
      diagnostic problems in terms of characterization, especially when small and
      hypoechoic to the rest of the parenchyma. Contrast--enhanced ultrasonography
      (CEUS) has shown its value in the characterization of focal liver lesions. This
      study assessed the value of the sinusoidal phase of CEUS with a second-generation
      contrast agent in the characterization of focal liver lesions to distinguish
      benign from malignant. Two hundred hepatic lesions with suspicious features at
      baseline ultrasound were prospectively studied with CEUS. Sensitivity,
      specificity, positive and negative predictive values, and diagnostic accuracy of
      the sinusoidal phase in the characterization of benign versus malignant liver
      lesions were evaluated. Hypoechogenicity of the focal liver lesion, during the
      sinusoidal phase of CEUS, allowed the diagnosis of malignancy with a sensitivity
      of 85%, specificity of 88%, positive predictive value of 92%, negative predictive
      value of 77%, and diagnostic accuracy of 86%. The diagnostic confidence in the
      diagnosis of malignancy significantly increased, with receiver operating
      characteristic curve areas from 0.536 for baseline ultrasound to 0.902 for the
      sinusoidal phase of CEUS.

PMID- 16802202
TI  - The production of Bacillus cereus enterotoxins is influenced by carbohydrate and
      growth rate.
AB  - Enterotoxin production is a key factor in Bacillus cereus food poisoning. Herein,
      the effect of the growth rate (mu) on B. cereus toxin production when grown on
      sucrose was studied and the Hemolytic BL enterotoxin (HBL) and nonhemolytic
      enterotoxin (Nhe) production by B. cereus was compared according to carbohydrate
      at mu = 0.2 h(-1). The anaerobic growth was carried out on continuous cultures in
      synthetic medium supplemented with glucose, fructose, sucrose, or an equimolar
      mixture of glucose and fructose. Concerning the HBL and Nhe enterotoxin
      production: (1) the highest enterotoxin production has occurred at mu = 0.2 h(-1)
      when growing on sucrose; (2) HBL production was repressed when glucose was
      consumed and the presence of fructose (alone or in mixture) cancelled glucose
      catabolite repression; (3) the consumption of sucrose increased Nhe production,
      which was not affected by the catabolite repression. Furthermore, analysis of the
      fermentative metabolism showed that whatever the mu or the carbon source, B.
      cereus used the mixed acid fermentation to ferment the different carbohydrates.
      The enterotoxin productions by this strain at mu = 0.2 h(-1) are highly
      influenced by the carbohydrates that do not involve any fermentative metabolism
      changes.

PMID- 16802204
TI  - High prevalence of multidrug resistance and random distribution of mobile genetic
      elements among uropathogenic Escherichia coli (UPEC) of the four major
      phylogenetic groups.
AB  - One hundred and ten UTI Escherichia coli strains, from Ljubljana, Slovenia, were
      analyzed for antibiotic resistances, mobile DNA elements, serotype, and
      phylogenetic origin. A high prevalence of drug resistance and multidrug
      resistance was found. Twenty-six percent of the isolates harbored a class 1
      integron, while a majority of the strains (56%) harbored rep sequences
      characteristic of F-like plasmids. int as well as rep sequences were found to be
      distributed in a random manner among strains of the four major phylogenetic
      groups indicating that all groups have a similar tendency to acquire and maintain
      mobile genetic elements frequently associated with resistance determinants.

PMID- 16802205
TI  - Spectroscopic and scanning electron microscopy studies of bioaccumulation of
      pollutants by algae.
AB  - The ability of Chlorella species and two other algal blooms collected locally to
      take up Cu(+2) and Ni(+2) was investigated using infrared and scanning electron
      microscopy (SEM) data. The percentage of metal uptake was determined with atomic
      absorption spectroscopy. The effects of pH and initial concentrations of metal
      ions on bioaccumulation were examined. The uptake of methyl orange dye by
      Chlorella species was also studied using Langmuir and Freundlich adsorption
      isotherms.

PMID- 16802206
TI  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) serves as a carbon and energy
      source for a mixed culture under anaerobic conditions.
AB  - We studied the anaerobic biodegradation of hexahydro-1,3,5-trinitro-1,3,5
      triazine (RDX) in a mineral medium by a mixed culture. RDX degradation activity
      was maintained for more than a year with only the addition of RDX. We observed a
      steady increase in the protein concentration of the culture from 4.8 microg mL(
      1) to more than 24.4 microg mL(-1), a >400% increase. There was only a slight
      increase in protein in the RDX unamended control bottles containing live culture,
      increasing from 4.8 microg mL(-1) to 7.8 microg mL(-1). Radiolabeled (14)C-RDX
      confirmed mineralization of the cyclic nitramine to (14)CO(2). After 164 days,
      35% of the radiolabel was recovered as 14CO2. This is the first report
      demonstrating the mineralization of RDX when it serves as a growth substrate for
      a mixed culture.

PMID- 16802207
TI  - Purification and characterization of an alginate lyase from marine Bacterium
      Vibrio sp. mutant strain 510-64.
AB  - Marine Vibrio sp. 510 was chosen as a parent strain for screening high producers
      of alginate lyase using the complex mutagenesis of Ethyl Methanesulphonate and UV
      radiation treatments. The mutant strain Vibrio sp. 510-64 was selected and its
      alginate lyase activity was increased by 3.87-fold (reaching 46.12 EU/mg) over
      that of the parent strain. An extracellular alginate lyase was purified from
      Vibrio sp. 510-64 cultural supernatant by successive fractionation on DEAE
      Sepharose FF and two steps of Superdex 75. The purified enzyme yielded a single
      band on SDS-PAGE with the molecular weight of 34.6 kDa. Data of the N-terminal
      amino acid sequence indicated that this protein might be a novel alginate lyase.
      The substrate specificity results demonstrated that the alginate lyase had the
      specificity for poly G block.

PMID- 16802208
TI  - Investigation of the role of a conserved glycine motif in the Saccharomyces
      cerevisiae xylose reductase.
AB  - All yeast xylose reductases, with the exception of that from Schizosaccharomyces
      pombe, possess the catalytic and coenzyme-binding elements from both the aldo
      keto reductase and short-chain dehydrogenase-reductase (SDR) enzyme families in
      their primary sequences. In the Saccharomyces cerevisiae xylose reductase (XR),
      the SDR-like coenzyme-binding GXXXGXG motif (Gly motif) is located between
      residues 128 and 134, with the third Gly residue being replaced by an Asp. We
      used site-directed mutagenesis to study the role of this SDR-like Gly motif in
      the S. cerevisiae xylose reductase. Site-directed mutagenesis of the individual
      conserved Gly residue positions (G128A, G132A, D134G, and D134A) did not
      significantly affect the specific activity, kinetic constants (K(m), K(cat), and
      K(cat)/K(m)), or dissociation constants (K(d)) in any of the variants compared
      with the wild type. Deletion of the entire Gly motif produced an unstable protein
      that could not be purified. These results indicate that the SDR-like Gly motif
      likely provides support to the overall structure of the enzyme, but it does not
      contribute directly to coenzyme binding in this XR.

PMID- 16802209
TI  - Screening of compactin-resistant microorganisms capable of converting compactin
      to pravastatin.
AB  - A simple method of using compactin for effective screening of microbial strains
      with high hydroxylation activity at the 6beta position of compactin was
      developed. Agar plates containing different carbon sources and 500 microg
      compactin mL(-1) were used to screen the microorganisms that can convert
      compactin to pravastatin. About 100 compactin-resistant strains were isolated
      from the Basal agar containing 7% (w/v) mannitol as a carbon source, in which two
      bacteria, Pseudomocardia autotrophica BCRC 12444 and Streptomyces griseolus BCRC
      13677, capable of converting compactin to pravastatin with the yield of 20 and
      32% (w/w), respectively, were found. High-performance liquid chromatography using
      C-18 column and two sequential mobile phases, 30% and 50% (v/v) acetonitrile, was
      also established to simultaneously determine the concentration of compactin and
      pravastatin in the culture broth. As such, about 2% of target microorganisms
      could be obtained from the screening program.

PMID- 16802210
TI  - Subintimal angioplasty of supra- and infrageniculate arteries.
AB  - We retrospectively reviewed our experience with subintimal angioplasty for
      chronic limb ischemia. Hospital records and films of all subintimal angioplasty
      procedures performed between October 2002 and December 2004 were reviewed and
      analyzed for demographic data, clinical data, and comorbid condition status.
      Thirty-nine subintimal angioplasties were performed in 37 patients (65% male, 35%
      female), with a median age of 73 years. Median follow-up was 9 months. The 30-day
      mortality rate was 8%. All-cause mortality was 33% after 24 months. In 23 cases
      (59%), a subintimal angioplasty of the superficial femoral artery (SFA) alone was
      performed. Both the SFA and popliteal/crural vessels were used in nine limbs
      (23%), the popliteal artery alone in three limbs (8%), and the crural arteries
      alone in four limbs (10%). Initial technical and clinical success rates were 67%
      and 49%, respectively. The complication rate was 28%. Twenty-four additional
      surgical interventions were performed after the initial angioplasty procedure, of
      which 12 were major amputations. Amputation-free survival (limb-salvage rate) was
      69% at 12 months [95% confidence interval (CI) 52-85%], and overall survival was
      69% (95% CI 52-85%) at 12 months. In patients with critical limb ischemia,
      subintimal angioplasty is feasible and in most cases technically successful. In
      these high-risk patients, often with combined cardiac, pulmonary, and diabetic
      risk and considered unfit for bypass surgery, subintimal angioplasty offers a
      safe and effective alternative.

PMID- 16802211
TI  - A nonrandomised controlled trial of endovenous laser therapy and surgery in the
      treatment of varicose veins.
AB  - Endovenous laser therapy (EVLT) is a minimally invasive treatment for varicose
      veins. This study compares early quality-of-life (QoL) outcomes following EVLT
      and surgery. Two nonrandomized groups were studied: an EVLT group with 70
      patients, median age 49 (interquartile range [IQR] 35-58) years, and a surgery
      group with 62 patients, median age 49 (IQR 35-61) years. Patients were assessed
      prior to and at 1, 6, and 12 weeks following the procedure using the Short Form
      36 (SF-36), the Aberdeen Varicose Veins Questionnaire (AVVQ), and the Venous
      Clinical Severity Score (VCSS). Follow-up at 1, 6, and 12 weeks was 100%, 77%,
      and 70% following EVLT and 100%, 85%, and 47% following surgery. SF-36 scores
      were significantly better in the EVLT group at 1 week (Physical Functioning, Role
      Physical, Bodily Pain, Vitality, and Social Functioning domains) and at 6 weeks
      (Physical Functioning and Role Physical). At 12 weeks, no significant differences
      were evident between the groups. AVVQ scores were significantly better in the
      EVLT group at 6 and 12 weeks. VCSS scores were significantly improved in both
      groups at 12 weeks. EVLT and surgery provide similar QoL improvements in patients
      with varicose veins. EVLT, however, removes the QoL limitations experienced by
      patients in the early postoperative period.

PMID- 16802212
TI  - EUS 2006. Proceedings of the 15th International Symposium on Endoscopic
      Ultrasound, 28-30 June 2006, Amsterdam, The Netherlands.

PMID- 16802213
TI  - EUS and EMR/ESD: is EUS in patients with Barrett's esophagus with high-grade
      dysplasia or intramucosal adenocarcinoma necessary prior to endoscopic mucosal
      resection?

PMID- 16802214
TI  - Nodal staging: number or site of nodes? How to improve accuracy? Is FNA always
      necessary? Junctional tumors--what's N and what's M?

PMID- 16802215
TI  - Staging stenotic oesophageal tumours: are CT and/or PET enough? Dilate or not?

PMID- 16802216
TI  - Reassessment of patients with esophageal cancer after neoadjuvant therapy.

PMID- 16802217
TI  - State of the art lecture: EUS for esophageal tumors.

PMID- 16802218
TI  - Acute pancreatitis: the acute attack. Acute recurrent pancreatitis.

PMID- 16802219
TI  - Choledocholithiasis--a practical approach from the endosonographer.

PMID- 16802220
TI  - Chronic pancreatitis: focal pancreatitis or cancer? Is there a role for
      FNA/biopsy? Autoimmune pancreatitis.

PMID- 16802221
TI  - State of the art lecture: lithiasis and pancreatitis.

PMID- 16802222
TI  - Cystic pancreatic lesions: can we diagnose them accurately what to look for? FNA
      marker molecular analysis resection, surveillance, or endoscopic treatment?

PMID- 16802223
TI  - Bile duct cancers: what can EUS offer? Intraductal US, 3D-IDUS? FNA--is it
      possible?

PMID- 16802224
TI  - Molecules and markers for endosonographers: what do we need to know and measure?

PMID- 16802225
TI  - Small pancreatic lesions: is there need for EUS-FNA preoperatively? What to do
      with the incidental lesions?

PMID- 16802226
TI  - State of the art lecture: endoscopic ultrasound (EUS) and FNA in pancreatico
      biliary tumors.

PMID- 16802227
TI  - Teaching and credentialing in France.

PMID- 16802228
TI  - The role of simulators, models, phantoms. Where's the evidence?

PMID- 16802229
TI  - Quality, competency and endosonography.

PMID- 16802230
TI  - State of the art lecture: endoscopic ultrasonography: training and competence.

PMID- 16802231
TI  - EUS for unexplained mediastinal lesions.

PMID- 16802232
TI  - Lung cancer patients with small nodes on CT--what's the next step?

PMID- 16802233
TI  - Competition for EUS (a) EBUS-TBNA (b) video assisted thoracoscopy.

PMID- 16802234
TI  - State of the art lecture: mediastinal EUS.

PMID- 16802235
TI  - EUS-guided fine needle injection (FNI) and anti-tumor therapy.

PMID- 16802236
TI  - Interventional EUS: difficult pancreaticobiliary access.

PMID- 16802237
TI  - EUS--experimental and evolving techniques.

PMID- 16802238
TI  - Looking forward--what will EUS be doing in 10 years?

PMID- 16802239
TI  - EBUS-TBNA for the diagnosis and staging of lung cancer.

PMID- 16802240
TI  - EUS-FNA and EBUS-TBNA; the pulmonologist's and surgeon's perspective.

PMID- 16802241
TI  - Towards complete endoscopic staging of the mediastinum?

PMID- 16802242
TI  - EUS-FNA and biomarkers for the staging of non-small cell lung cancer.

PMID- 16802243
TI  - State of the art lecture: EUS and EBUS in pulmonary medicine.

PMID- 16802244
TI  - Standard visualization of biliopancreatic system by EUS.

PMID- 16802245
TI  - Effects of vascular occlusion on maximal force, exercise-induced T2 changes, and
      EMG activities of quadriceps femoris muscles.
AB  - The purpose of our study was to determine the effect of vascular occlusion on
      neuromuscular activation and/or the energy metabolic characteristics of the
      quadriceps femoris (QF) muscles during muscle contractions. Seven men
      participated in the study. An occlusion cuff was attached to the proximal end of
      the right thigh, so that blood flow in the anterior medial malleolar artery was
      reduced to approximately 88 % of the non-occluded flow. Muscle functional
      magnetic resonance imaging and maximal voluntary contraction (MVC) were carried
      out before and immediately after 5 sets of 10 repetitions of knee extension
      exercises at 50 % of the 10 repetitions maximum, from which transverse relaxation
      times (T2) and maximal force were measured, respectively. Integrated
      electromyography (iEMG) activity was recorded from the belly of the rectus
      femoris, vastus lateralis, and vastus medialis muscles during MVC and repetitive
      exercises. The percentage change in T2 was significantly increased for individual
      QF muscles, and there was a significant increase in iEMG activity over the 5 sets
      of repetitive exercises under conditions of vascular occlusion, but there was no
      significant effect on isometric force and iEMG activity during MVC. These results
      are consistent with the idea that there is greater osmolite accumulation during
      exercise with occlusion, although increased neural activation cannot be ruled
      out.

PMID- 16802246
TI  - Oxygen uptake kinetics during heavy submaximal exercise: Effect of sickle cell
      trait with or without alpha-thalassemia.
AB  - Sickle cell trait (SCT) is a genetic disease affecting the synthesis of normal
      hemoglobin (Hb) marked by the heterozygous presence of HbA and HbS. It is thought
      that exercise tolerance and aerobic capacity could be limited in SCT carriers,
      but that the co-existence of alpha-thalassemia with SCT (SCTAT) could improve
      exercise response. To examine these issues, we compared the characteristics of
      VO2 kinetics during a constant heavy exercise among athletes carrying either the
      SCT (n = 6), the SCTAT (n = 9), or the normal Hb (control group; n = 10). After
      determination of maximal power output (Ppeak), all subjects underwent a constant
      heavy cycling exercise lasting 9 min at approximately 70 % Ppeak. Pulmonary VO2
      and cardio-respiratory parameters were measured breath-by-breath and the VO2
      response was modelled using non-linear regression techniques. The time constant
      of the VO2 primary component and oxygen deficit were not significantly different
      among the three groups. The VO2 slow component was 28 % and 33 % higher (p <
      0.05) in SCT and SCTAT than in the control groups, respectively. Altogether,
      athletes with the SCT and the SCTAT had higher heart rate at the beginning (+ 5.2
      %) and the end (+ 7.4 %) of the slow component compared to the control group (p <
      0.05). These results suggest that SCT and SCTAT subjects are not limited during
      the first exercise minutes, but are prone to exercise intolerance and to lower
      aerobic capacity thereafter, due to a higher VO2 slow component, and that alpha
      thalassemia does not improve exercise response. The finding of a higher slow
      component in SCT and SCTAT athletes was possibly due to the loss of O2
      availability to muscles, additional fiber recruitment and/or higher cardiac load
      with time.

PMID- 16802247
TI  - Rapid detection of anabolic steroids in urine by protein arrays.
AB  - The purpose of this study was to develop a rapid and sensitive method utilizing
      the state-of-the-art protein arrays technique to detect urinary anabolic steroids
      (ASs) in athletes. Three experiments were designed to investigate the feasibility
      of the protein arrays for ASs testing. Firstly, androgen receptor (AR) and
      estrogen receptor (ER) protein arrays were prepared on polysaccharide-coated
      slides to investigate whether they can bind to ASs (affinity tests). Secondly, in
      comparison to adrenergic receptor (the receptor of beta-blockers) and opioid
      receptor (the receptor of narcotic analgesics) arrays, AR and ER protein arrays
      were used to test whether they can determine the ASs positive urine sample
      specifically (specific binding tests). At last protein arrays were used to
      estimate qualitatively the ASs in positive urine samples (qualitative tests).
      From the results of the affinity tests the shape of the dose-dependence curve
      suggested a positive cooperative binding of ASs with the protein arrays. The AR
      and ER protein arrays showed affinities for fluorescence labelled testosterone
      and estradiol that were similar to those of literatures (0.65 vs. 0.89 nM, 5.96
      vs. 10.3 nM, respectively). Based on the data, the sensitivity of testing can
      reach 0.1 nM that was much better than the World Anti-Doping Code (WADA)
      standard. Specific binding tests showed that the prohibited substance in positive
      urine samples belonged to the anabolic estrogenic inhibitor of ASs. From the
      results of qualitative tests, we could estimate that there were anabolic
      androgenic steroids in the positive urine samples and their concentration was
      lower than 50 microM Methyltestosterone. The total time of the test process for
      ASs in urine needed less than 1 h. In summary, the present study showed that the
      protein arrays method provided a highly sensitive and rapid alternative to screen
      urine samples for the detection of the misuse of ASs in athletes and was suitable
      for testing in both weekly training sessions as well as large-scale competition
      events.

PMID- 16802248
TI  - Electromyostimulation and plyometric training effects on jumping and sprint time.
AB  - This study compared the effects of four-week training periods of
      electromyostimulation (EMS), plyometric training (P), or combined EMS and P
      training of the knee extensor muscles on 20 m sprint time (ST), jumping ability
      (Squat jump [SJ] and Countermovement jump [CMJ]), maximal isometric strength
      (MVC), and muscle cross-sectional area (CSA). Forty subjects were randomly
      assigned to one of the four treatment groups: electromyostimulation (EG),
      plyometric (PG), combined EMG, and P (EPG), that took place 4 times per week, and
      a control group (CG). Subjects were tested before and after the training program,
      as well as once more after 2 wk of detraining. A significant improvement (p <
      0.05) in ST was observed after training (2.4 %) in EG while a significant slowing
      (p < 0.05) was observed (- 2.3 %) in EPG. Significant increases in EPG (p < 0.05)
      were observed in SJ (7.5 %) and CMJ (7.3 %) after training, while no significant
      changes in both jumps were observed after training and detraining for EG. A
      significant increase (p < 0.05) in MVC was observed after training (9.1 %) and
      after detraining (8.1 %) in EG. A significant increase (p < 0.05) in MVC was
      observed after training (16.3 %) in EPG. A significant increase (p < 0.01) in CSA
      was observed after training in EG (9.0 %) and in EPG (7.1 %). EMS combined with
      plyometric training increased the jumping height and sprint run in physically
      active men. In addition, EMS alone or EMS combined with plyometric training leads
      to increase maximal strength and to some hypertrophy of trained muscles. However,
      EMS training alone did not result in any improvement in jumping explosive
      strength development or even interfered in sprint run.

PMID- 16802249
TI  - Spectral analysis of skin blood flowmotion before and after exercise in healthy
      trained and in sedentary subjects.
AB  - Cutaneous blood flowmotion (CBF) can contribute to a reduction in the resistance
      in skin microvascular networks. The increase of CBF during exercise can improve
      the capacity of skin microvascular networks to transport and eliminate heat. In
      order to verify if the physical training could increase the skin blood flowmotion
      during exercise, we performed spectral analysis of cutaneous forearm laser
      Doppler signal, before and after acute maximal exercise in 15 healthy trained
      subjects (TS) and in 15 control sedentary subjects (SS). Within the total
      spectrum of 0.009 - 2.3 Hz, five frequency intervals of CBF were analysed: 0.009 
      0.02 Hz (endothelial activity), 0.02 - 0.06 Hz (sympathetic activity), 0.06 -
      0.2 Hz (vascular myogenic activity), 0.2 - 0.6 Hz (respiratory activity), and 0.6
      - 2.3 Hz (heart activity). In basal conditions, no difference between TS and SS
      was observed in the cutaneous blood perfusion (CBP), expressed in conventional
      perfusion units (PU), and in the mean value of CBF total spectrum power density
      (PD), measured in PU/Hz, while the absolute PD of the endothelial and myogenic
      CBF components was significantly higher (p < 0.05) in TS (0.69 +/- 0.62 PU/Hz and
      0.47 +/- 0.43 PU/Hz, respectively) than in SS (0.29 +/- 0.16 PU/Hz and 0.23 +/-
      0.16 PU/Hz, respectively). In both TS and SS, acute exercise induced a
      significant increase of CBP mean value (30.91 +/- 20.28 PU, p < 0.0005 and 16.45
      +/- 7.02 PU, p < 0.0005; respectively) and of CBF total spectrum PD (6.65 +/-
      4.13 Hz/PU, p < 0.001 and 4.17 +/- 1.86 Hz/PU, p < 0.05; respectively), with a
      significant difference of these two parameters between the two groups (p < 0.05).
      After exercise, CBF components regarding endothelial and myogenic activities
      maintained a higher PD mean value in TS in respect to SS (1.69 +/- 1.34 PU/Hz and
      1.59 +/- 0.93 versus 0.91 +/- 0.44 and 0.98 +/- 0.48 PU/Hz respectively, p <
      0.05). These findings suggest that physical training is associated with the
      increase of CBF and particularly on its endothelial and myogenic components in
      response to exercise. This can favour a greater reduction of resistance in skin
      microvascular networks during exercise and consequently an increase of its
      capacity to transport and eliminate heat.

PMID- 16802250
TI  - Bioenergetics of a slalom kayak (k1) competition.
AB  - The aim of this study was: i) to compute an energy balance of a slalom kayak
      competition by measuring the percentage contributions of the aerobic and
      anaerobic energy sources to total metabolic power (E(tot)); and ii) to compare
      these data with those obtained, on the same subjects, over a flat-water course
      covered at maximal speed in a comparable time. Experiments were performed on
      eight middle- to high-class slalom kayakers (24.8 +/- 8.1 years of age, 1.75 +/-
      0.04 m of stature, and 69.8 +/- 4.7 kg of body mass) who completed the slalom
      race in 85.8 +/- 5.3 s and covered the flat water course in 88.1 +/- 7.7 s.
      E(tot) was calculated from measures of oxygen consumption and of blood lactate
      concentration: it was about 30 % larger during the flat water all-out test (1.72
      +/- 0.18 kW) than during the slalom race (1.35 +/- 0.12 kW). However, in both
      cases, about 50 % of E(tot) derives from aerobic and about 50 % from anaerobic
      energy sources. These data suggest that, besides training for skill acquisition
      and for improving anaerobic power, some high intensity, cardiovascular
      conditioning should be inserted in the training programs of the athletes
      specialised in this sport.

PMID- 16802251
TI  - Highly demanding resistive vibration exercise program is tolerated during 56 days
      of strict bed-rest.
AB  - Several studies have tried to find countermeasures against musculoskeletal de
      conditioning during bed-rest, but none of them yielded decisive results. We
      hypothesised that resistive vibration exercise (RVE) might be a suitable training
      modality. We have therefore carried out a bed-rest study to evaluate its
      feasibility and efficacy during 56 days of bed-rest. Twenty healthy male
      volunteers aged 24 to 43 years were recruited and, after medical check-ups,
      randomised to a non-exercising control (Ctrl) group or a group that performed RVE
      11 times per week. Strict bed-rest was controlled by video surveillance. The diet
      was controlled. RVE was performed in supine position, with a static force
      component of about twice the body weight and a smaller dynamic force component.
      RVE comprised four different units (squats, heel raises, toe raises, kicks), each
      of which lasted 60 - 100 seconds. Pre and post exercise levels of lactate were
      measured once weekly. Body weight was measured daily on a bed scale. Pain
      questionnaires were obtained in regular intervals during and after the bed-rest.
      Vibration frequency was set to 19 Hz at the beginning and progressed to 25.9 Hz
      (SD 1.9) at the end of the study, suggesting that the dynamic force component
      increased by 90 %. The maximum sustainable exercise time for squat exercise
      increased from 86 s (SD 21) on day 11 of the BR to 176 s (SD 73) on day 53 (p =
      0.006). On the same days, post-exercise lactate levels increased from 6.9 mmol/l
      (SD2.3) to 9.2 mmol/l (SD 3.5, p = 0.01). On average, body weight was unchanged
      in both groups during bed-rest, but single individuals in both groups depicted
      significant weight changes ranging from - 10 % to + 10 % (p < 0.001). Lower limb
      pain was more frequent during bed-rest in the RVE subjects than in Ctrl (p =
      0.035). During early recovery, subjects of both groups suffered from muscle pain
      to a comparable extent, but foot pain was more common in Ctrl than in RVE (p =
      0.013 for plantar pain, p = 0.074 for dorsal foot pain). Our results indicate
      that RVE is feasible twice daily during bed-rest in young healthy males, provided
      that one afternoon and one entire day per week are free. Exercise progression,
      mainly by progression of vibration frequency, yielded increases in maximum
      sustainable exercise time and blood lactate. In conclusion, RVE as performed in
      this study, appears to be safe.

PMID- 16802252
TI  - Changes in mucosal and humoral atopic-related markers and immunoglobulins in
      elite cyclists participating in the Vuelta a Espana.
AB  - Atopic-related factors, humoral and mucosal immunoglobulins (Ig), and cortisol
      were measured in 17 professional cyclists competing in the 2003 Vuelta a Espana
      (a three-week multi-stage race). Venous blood and saliva samples were obtained
      the morning before the start of the race (T0), on the first rest day after 10
      days of racing (T1), and before the start of the last stage after 21 days of
      racing (T2). Atopic-related factors, IgE, eosinophil cationic protein (ECP), and
      eosinophils, were significantly altered during the race. Serum IgE (T1: + 10 %)
      and ECP (salivary, T1: 113 % and serum, T2: 155 %) were significantly increased,
      while eosinophils (T1: - 32 %, T2: - 55 %) were significantly lower, than pre
      race levels. Salivary sIgA secretion rate was significantly decreased at T2 (- 36
      %). Pearson product-moment correlations revealed a modest correlation between
      salivary sIgA and salivary ECP (T1: r = 0.30; T2: r = 0.48; p < 0.01). Serum IgM,
      total IgG, IgG1, IgG2, IgA levels, at T1 and T2, and cortisol at T2, were
      significantly lower than pre-race levels. In conclusion, the elevation in IgE and
      ECP suggests an up-regulation of atopic-related factors in professional cyclists
      participating in the Vuelta a Espana. The correlation between salivary sIgA and
      salivary ECP indicates a role for sIgA in mediating mucosal inflammation. The
      alterations in Ig levels may indicate Ig isotype switching. An increasing state
      of hormonal fatigue may have influenced the observed immune alterations.

PMID- 16802253
TI  - Chronic L-arginine supplementation enhances endurance exercise tolerance in heart
      failure patients.
AB  - The purpose of the study was to determine the potential beneficial effect of six
      weeks oral L-arginine supplementation (LAS) on endurance exercise, an important
      determinant of daily-life activity in patients with chronic stable heart failure
      (CHF). After an initial incremental maximal exercise test, CHF patients performed
      an identical thirty-minute interval endurance exercise test before and after six
      weeks with (L-arginine group; ARG) or without LAS (control group; CTL).
      Hemodynamic, respiratory, and metabolic parameters were determined at rest,
      during exercise, and during recovery. Mean heart rate decreased throughout
      exercise and recovery after LAS (- 8.2 +/- 1.4 b x min(-1); p = 0.003 and - 6.7
      +/- 1.6 b x min(-1); p < 0.001, respectively), systemic blood pressure and
      respiratory parameters remaining unchanged. Resting L-argininaemia increased from
      102 +/- 11 to 181 +/- 37 micromol x l(-1) (p < 0.004) and exercise-induced peak
      increase in plasma lactate was blunted after LAS (4.13 +/- 0.75 vs. 3.13 +/- 0.39
      mmol x l(-1); p = 0.02). No significant change was observed in the control group.
      In heart failure patients, six weeks oral LAS enhances endurance exercise
      tolerance, reducing both heart rate and circulating lactates. This suggests that
      chronic LAS might be useful as a therapeutic adjuvant in order to improve the
      patient's physical fitness.

PMID- 16802254
TI  - Combined aerobic and resistance training in breast cancer survivors: A
      randomized, controlled pilot trial.
AB  - The purpose of this pilot study was to examine the effects of a combined
      cardiorespiratory and resistance exercise training program of short duration on
      the cardiorespiratory fitness, strength endurance, task specific functional
      muscle capacity, body composition and quality of life (QOL) in women breast
      cancer survivors. Sixteen subjects were randomly assigned to either a training (n
      = 8; age: 50 +/- 5 yrs) or control non-exercising group (n = 8; age: 51 +/- 10
      yrs). The training group followed an 8-week exercise program consisting of 3
      weekly sessions of 90-min duration, supervised by an experienced investigator and
      divided into resistance exercises and aerobic training. Before and after the
      intervention period, all of the subjects performed a cardiorespiratory test to
      measure peak oxygen uptake (VO2peak), a dynamic strength endurance test (maximum
      number of repetitions for chest and leg press exercise at 30 - 35 % and 100 - 110
      % of body mass, respectively) and a sit-stand test. Quality of life was assessed
      using the European Organization for Research and Treatment of Cancer QLQ-C30
      (EORTC-C30) questionnaire. In response to training, QOL, VO2peak (mean 3.9
      ml/kg/min; 95 % CI, 0.93, 6.90) performance in leg press (17.9 kg; 95 % CI, 12.8,
      22.4) and sit-stand test (- 0.67 s; 95 % CI, - 0.52, - 1.2) improved (p < or =
      0.05). We observed no significant changes in the control group. Combined
      cardiorespiratory and resistance training, even of very brief duration, improves
      the QOL and the overall physical fitness of women breast cancer survivors.

PMID- 16802255
TI  - Snuff use and smoking in Finnish olympic athletes.
AB  - This study aimed to assess the prevalence of smoking and snuff use in Finnish
      elite athletes. Of all the athletes (n = 494) financially supported by the
      National Olympic Committee, 446 completed a structured questionnaire (response
      rate 90.3 %) in 2002. A control group (n = 1504, response rate 80.2 %) comprised
      an age-matched sample from the population-based sample collected by the National
      Public Health Institute. Any smoking was reported by 11.4 % of the athletes (3.6
      % daily and 7.8 % occasionally) and by 38.3 % of the controls (28.1 % and 10.2
      %). After adjusting for age, sex, and education, OR (95 % CI) for any smoking was
      highest 0.42 (0.23 - 0.77) for athletes in skill-based events and lowest 0.06
      (0.02 - 0.17) for endurance athletes as compared with controls. Snuff use was
      reported by 24.6 % of the athletes (9.6 % daily and 15.0 % occasionally) and by
      3.7 % of the controls (1.8 % and 1.9 %). The adjusted OR (95 % CI) for any snuff
      use was highest 15.6 (9.55 - 25.6) for team-sport athletes and lowest 3.33 (1.54 
      7.21) for endurance athletes as compared with controls. Although snuff use in
      the general female population is rare, also female athletes did use snuff. Though
      prevalence of daily smoking among athletes was one-seventh of the respective
      figure for the general population, prevalence of daily snuff use was five-fold
      that of controls. Tobacco free elite athletes are valuable in health counselling
      because athletes are considered role models influencing their peers and the
      sport. Sport associations are challenged to ban all forms of tobacco.

PMID- 16802256
TI  - Increased susceptibility to plasma lipid peroxidation in untrained subjects after
      an extreme mountain bike challenge at moderate altitude.
AB  - The purpose of this study was to determine whether acute strenuous physical
      exercise, partially performed under moderate altitude, influences the
      susceptibility of plasma lipids to peroxidation. Eleven male amateur cyclists
      took part in a 95-km mountain bike challenge with a cumulative altitude
      difference of 2340 m. Blood samples were obtained before and immediately after
      the race in order to determine plasma lipid and lipoprotein concentrations, and
      to assess the susceptibility of the former to peroxidation. Neither plasma lipid
      nor lipoprotein levels changed significantly after the race. However, the
      susceptibility of plasma lipids to peroxidation increased by 71.8 %. We concluded
      that strenuous physical exercise partially performed under hypoxic conditions
      increases the susceptibility of plasma lipids to peroxidation in untrained
      subjects.

PMID- 16802257
TI  - [The police - there to serve and protect].

PMID- 16802258
TI  - [For: is monotherapy the gold standard of psychopharmacology?].

PMID- 16802259
TI  - [Predictive diagnostics in chorea huntington: psychotherapeutic implications for
      counselling].
AB  - The progress in molecular genetic research leads to an increased availability of
      predictive diagnosis of inherited diseases. However, the prediction of an
      incurable illness is inevitably related with severe psychic conflicts. Based on
      the relevant literature, the psychological implications of predictive diagnostics
      are outlined, and counselling strategies for persons vulnerable for an inherited
      disease are summarized. In spite of numerous studies with persons at risk the
      prediction of the individual reaction remains rather difficult. Unconscious
      expectations play an essential, but underestimated role for the test motivation
      and coping strategies. Relieving the pressure of time supposed by most of the
      risk persons seems necessary to allow a deeper understanding of motivation and
      development of sound coping strategies. After disclosure of the test result, an
      ongoing counselling should be offered to all family members.

PMID- 16802260
TI  - [How to care for homeless mentally ill men in the community - a randomised
      intervention study].
AB  - OBJECTIVE: The aim of the present study was to clarify whether the mediation of
      homeless persons identified as mentally ill into the sociopsychiatric or the help
      seeking system can be facilitated by a short-term intervention. METHOD: Probands
      with at least one psychiatric diagnosis according to ICD-10 (73 % of the sample)
      were randomized to the intervention group (manualized procedure with five brief
      contacts) or to the control group (no intervention). The course of the contacts
      and the further help-seeking behavior after 4 and 8 months were registered.
      RESULTS: The very sporadic participation of the patients in the therapeutic
      discussion permitted a manualized procedure in individual cases only. The
      establishment of contact was very successful, but the problem-centered procedure
      only within limits. The intergroup comparison revealed no fundamental differences
      in the utilization of offers of support during the course of the study. Overall,
      however, the number of users tended to increase, with an increased contact
      frequency being recorded especially among those participating in therapeutic
      discussions. CONCLUSIONS: Only a relatively small proportion of the clientele can
      be reached through short-term behavior therapy. Fundamentally a low-profile,
      primarily outreach-based offer founded on longer-term contact appears to be more
      promising.

PMID- 16802261
TI  - [Predictors of the discharge status in acute day-hospital and inpatient care - a
      comparison between the two settings within a randomised controlled trial].
AB  - OBJECTIVE: To search for predictors of the discharge status in day-hospital
      patients and inpatients, within a randomized controlled trial on the
      effectiveness of acute psychiatric day hospital treatment as compared to
      inpatient treatment. METHOD: The study was conducted at the Department of
      Psychiatry and Psychotherapy, Dresden University of Technology. Regression
      analyses assessing the relationship between theoretically chosen predictor
      variables and the discharge status as measured using the Brief Psychiatric Rating
      Scale (BPRS 4.0) were conducted on a sample of 69 day-hospital patients and a
      sample of 76 inpatients. RESULTS: In both settings, admission status was the
      strongest predictor of discharge status. As concerns day-hospital patients, those
      suffering from a personality disorder as well as those showing a higher degree of
      social disability were discharged with a higher level of psychopathological
      symptoms. Among inpatients, those suffering from an anxiety, obsessive
      compulsive, or adjustment disorder as well as those being retired or unemployed
      benefited less from treatment. CONCLUSIONS: Given the explorative character of
      the present study, further prospective studies are needed in order to cross
      validate findings on the potential criteria for allocating acute mentally ill
      either to day-hospital or inpatient treatment.

PMID- 16802262
TI  - [Social psychiatry and psychoanalysis - "immature, jostling and rivaling
      siblings"?].
AB  - AIM: We want to determine the influence of psychoanalysis on social psychiatry
      today and 30 years ago. METHOD: Systematic analyses of all articles appearing in
      Psychiatrische Praxis in 1974, 1975, 2004, and 2005. RESULTS: While almost one in
      five articles referred to psychoanalysis or Freud 30 years ago, currently this
      hardly occurs at all. CONCLUSION: The social-scientific claims of psychoanalysis
      often heard in the 1970 s play no role in current social psychiatry.
      Psychoanalysis is also losing significance as a method of social psychiatric
      patient care.

PMID- 16802263
TI  - [Diagnosis and treatment of the attention-deficit/hyperactivity syndrome (ADHS)
      in adults with drug addiction in in-patient and out-patient setting].
AB  - OBJECTIVE: Children with untreated ADHS have a high risk of becoming adult
      addicts and often present as problem patients on psychiatric detoxification
      units. We present our experience with the task of recognizing ADHS and initiating
      treatment during the short period of in-patient detoxification. METHODS: Typical
      case histories illustrate the structural framework of the setting, the diagnosis
      and therapeutic process and the course of treatment. RESULTS: Assessment of ADHS
      and initiation of specific treatment during in-hospital care is practical and
      useful to stop further chronification of illness. CONCLUSION: This work requires
      a new approach to these often difficult patients by establishing a continuous
      therapeutic milieu.

PMID- 16802264
TI  - [To hide and to reveal - how to manage the stigma of mental illness].
AB  - The biography of a social-worker shows a positive development in her professional
      life in spite of several severe episodes of psychotic illness. The author knows
      her personally over three decades, partly as her psychiatrist. Whether to hide or
      reveal her psychotic illness as a stigma in professional life is discussed with
      her own examples. Her "management of the secret" is shown as a combination of
      hiding and revealing. A slow process of taking again the "risk of trust" with a
      few friends and within the therapeutic process helps her gain back selfconfidence
      and trust in others. This process is discussed with Luhmanns approach to trust
      and the current literature as a way to overcome the inner process of
      stigmatisation.

PMID- 16802265
TI  - A randomized controlled trial comparing the accuracy of general diagnostic upper
      gastrointestinal endoscopy performed by nurse or medical endoscopists.
AB  - BACKGROUND AND STUDY AIMS: Rising demand for general diagnostic upper
      gastrointestinal endoscopy in the UK is outgrowing the capacity of doctors to
      provide this service within a reasonable time. One solution is to train nurses to
      carry out the procedure, but it is not known whether nurses can perform general
      diagnostic upper gastrointestinal endoscopy as competently as doctors. PATIENTS
      AND METHODS: A randomized controlled non-inferiority trial compared the adequacy
      and the accuracy of diagnostic upper gastrointestinal endoscopies performed by
      five medical and two nurse endoscopists. The videotaped procedures were assessed
      by a consultant gastroenterologist blinded to the identity of the endoscopist.
      RESULTS: 641 patients were randomly allocated (before attendance and consent
      procedure) to endoscopy carried out either by a doctor or a nurse. Of these, 412
      were enrolled and 367 (89 %) were included in the analysis. An adequate view was
      obtained throughout in 53.4 % (93/177) of doctor endoscopies and 91.6 % (174/190)
      of nurse endoscopies (difference 38.2 %, 95 % CL 30.5 %, 47.2 %). In adequately
      viewed areas, the mean agreement between doctor and expert was 81.0 % and between
      nurse and expert it was 78.3 % (difference between the means 2.7 %, 95 % CL - 1.0
      %, 6.4 %). There was no difference between doctors and nurses in the rate of
      biopsy performance (90.4 % and 91.1 %, respectively, P = 0.862). Nurses took
      longer (8.1 minutes vs. 4.6 minutes, P < 0.001) and used intravenous sedation
      more often (57.6 %, P = 0.027). Adequacy of view correlated positively with
      endoscopy duration ( P < 0.001), but diagnostic accuracy correlated inversely
      with duration ( P < 0.001). Neither adequacy or accuracy correlated significantly
      with use of intravenous sedation. CONCLUSIONS: In endoscopies performed by
      nurses, the proportion of adequate examinations was much higher than that found
      for doctors. In areas with an adequate view, there is no significant difference
      in accuracy between nurses and doctors. Nurses can provide an accurate general
      diagnostic upper gastrointestinal endoscopy service as competently as doctors.

PMID- 16802266
TI  - Diagnostic and prognostic implications of DNA ploidy and S-phase evaluation in
      the assessment of malignancy in biliary strictures.
AB  - BACKGROUND AND STUDY AIMS: Brush cytology of biliary strictures has a low
      sensitivity for diagnosing malignancy, and additional diagnostic tools are
      needed. The aim of the present study was to assess the diagnostic and prognostic
      importance of DNA measurements as an adjunct to brush cytology in patients with
      biliary strictures. PATIENTS AND METHODS: All patients (n = 225) with bile duct
      strictures who underwent endoscopic retrograde cholangiopancreatography (ERCP)
      between January 1997 and October 2003 at the Department of Radiology at
      Karolinska University Hospital, Huddinge, Sweden, were included in the study.
      While 66 patients had an unclear final diagnosis and were therefore excluded, the
      remaining 159 patients were assessed with brush cytology and DNA flow cytometry.
      RESULTS: Sensitivity and specificity of DNA aneuploidy for tumor detection were
      43 % and 96 %. Using DNA analysis in addition to brush cytology, the sensitivity
      was 62 % compared with 57 % for brush cytology alone (not significant). Patients
      with diploid DNA tumors had a significantly better survival than patients with
      aneuploid DNA tumors ( P = 0.02). The mean survival was 10 months for diploid
      cancers and 6 months for aneuploid cancers. CONCLUSION: DNA ploidy measurement
      may be a diagnostic method that could supplement brush cytology in the
      identification of malignancy in biliary strictures. DNA aneuploidy is a marker of
      poor prognosis in patients with malignant biliary strictures.

PMID- 16802267
TI  - Argon plasma ablation of gastric inlet patches in the cervical esophagus may
      alleviate globus sensation: a pilot trial.
AB  - BACKGROUND AND STUDY AIMS: Globus sensation and/or sore throat have been
      associated with both gastroesophageal reflux disease and the presence of a
      gastric inlet patch. There have been no reports, however, on whether ablation of
      heterotopic mucosa in the cervical esophagus leads to improvement of chronic
      globus sensation. PATIENTS AND METHODS: Ten patients with a histologically proved
      gastric inlet patch who complained of chronic globus sensation and/or sore throat
      were included in this prospective pilot study. After a thorough assessment,
      including videofluoroscopy, laryngoscopy, manometry, and 24-hour two-channel pH
      monitoring, patients underwent argon plasma coagulation (APC) to ablate the
      heterotopic mucosa. A questionnaire with a visual analog scale ranging from 0 to
      10 was used for assessment of globus sensation, sore throat, and other typical or
      atypical reflux symptoms. Follow-up examinations (including symptom assessment)
      were performed 4 weeks and 8 weeks after APC therapy. RESULTS: Ablation of the
      gastric inlet patch resulted in a significant reduction of median symptom scores
      for globus sensation (from 2.7 to 0) and sore throat (from 2.8 to 0) 8 weeks
      after therapy ( P < 0.05), but there was no improvement in other reflux-related
      symptoms. Acid reflux in the distal and proximal esophagus, determined by two
      channel pH monitoring, did not change after therapy. CONCLUSIONS: Our preliminary
      data suggest that ablation of gastric inlet patches by APC can alleviate chronic
      globus sensation or sore throat. Acid reflux or its treatment is unlikely to
      influence these results. A randomized and blinded study is warranted.

PMID- 16802268
TI  - Recurrence rate of anastomotic biliary strictures in patients who have had
      previous successful endoscopic therapy for anastomotic narrowing after orthotopic
      liver transplantation.
AB  - BACKGROUND AND STUDY AIMS: The development of anastomotic strictures is one of
      the most common complications of orthotopic liver transplantation (OLT) with
      choledochocholedochostomy anastomosis. Endoscopic therapy with balloon dilation
      and/or stent placement is an effective therapy. The aim of this study was to
      assess the recurrence rate of anastomotic strictures and the features that
      predict recurrence after previously successful endoscopic therapy. PATIENTS AND
      METHODS: We searched the endoscopic retrograde cholangiopancreatography (ERCP)
      database for all patients who had had an OLT who were undergoing ERCP. The study
      cohort consisted of post-OLT patients who had a recurrence of anastomotic
      stricture after initial resolution following a course of endoscopic therapy.
      RESULTS: A total of 916 OLT operations were performed during the study period
      from June 1994 to November 2004. Out of this group, 143 patients (15.6 %) were
      diagnosed with anastomotic stricture and underwent a total of 423 ERCPs for
      endoscopic treatment. Twelve patients who are still undergoing endoscopic therapy
      were excluded from the analysis. The technical success rate was 96.6 %, and the
      endoscopic therapy was successful in 82 % of patients; 18 % had a recurrence of
      cholestasis and ERCP revealed a recurrence of the anastomotic stricture that
      required intervention. The mean time of follow-up after stent removal was 28
      months (range 1 - 114 months). The study did not reveal any clinical or
      endoscopic parameters that could predict recurrence, though the presence of a
      biliary leak at initial ERCP and a longer time to initial presentation were
      factors that showed a trend toward an increased likelihood of recurrence.
      CONCLUSIONS: Biliary strictures remain a common complication after OLT, and in
      nearly one in five patients these strictures recur after initially successful
      endoscopic therapy. There were no clinical or endoscopic parameters identified in
      this study that predicted recurrence. Further study is needed to determine what
      type of endoscopic therapy would minimize the risk of stricture recurrence.

PMID- 16802269
TI  - "Hemodynamic efficacy" of two endoscopic clip devices used in the treatment of
      bleeding vessels, tested in an experimental setting using the compact Erlangen
      Active Simulator for Interventional Endoscopy (compactEASIE) training model.
AB  - BACKGROUND AND STUDY AIMS: Hemoclip therapy is a well-established procedure in
      the treatment of gastrointestinal bleeding. Although new products are provided
      periodically by the industry, comparative investigations are lacking. We compared
      two different hemoclip devices in an experimental setting, assessing them using
      objective hemostatic parameters. MATERIALS AND METHODS: We compared two
      disposable clip devices (Olympus HX-200L-135 (n = 40) vs. Wilson-Cook Tri-Clip (n
      = 40)) in an experimental setting using the compact Erlangen Active Simulator for
      Interventional Endoscopy (compactEASIE) training model equipped with an upper
      gastrointestinal-organ package for bleeding simulation. This was a randomized,
      prospective, controlled trial. Four investigators with different levels of
      endoscopic experience applied ten hemoclip devices of each type to the spurting
      vessels, the clips allocated using a randomized list for each investigator. The
      efficacy of hemostasis was determined by continuous measurement of the pressure
      within the afferent vessel before and after clip application and calculation of
      the relative reduction of vessel diameter by the clip device. The system pressure
      was recorded over the period from 1 minute before to 1 minute after clip
      application. A secondary end point was a subjective assessment of the whole clip
      application procedure by the endoscopist and the assisting nurse, using a visual
      analog scale (0 - 100, with 100 representing the best experience). RESULTS: A
      total of 39/40 clips of each type were applied successfully. Both clip devices
      led to a significant increase in system pressure, representing significant
      relative reduction of vessel diameter (Olympus 5.4 +/- 7.5 %, p < 0.001; Cook 4.9
      +/- 8.0 %, p < 0.001). Overall, there was no significant difference between the
      two devices ( P = 0.756). However, the investigator with the least experience in
      endoscopy (< 100 procedures) produced significantly inferior results compared
      with the other three investigators, who had performed between 2000 and 6000
      procedures each ( P < 0.05). We found no evidence of a learning curve from the
      intra-observer results. The devices received good, but not significantly
      different, overall ratings by the endoscopists (Olympus 69 +/- 24 vs. Wilson-Cook
      65 +/- 16) and by the assisting nurses (Olympus 77 +/- 9 vs. Wilson-Cook 70 +/-
      22). CONCLUSIONS: Using an established cadaveric training model, no significant
      difference was found between the two types of hemoclip devices with respect to
      their "hemostatic efficacy". However, the experience of the endoscopist appears
      to play a major role in successful clip application. The use of a feedback
      mechanism in emergency endoscopy training, using continuous intravessel pressure
      monitoring, may substantially enhance the efficacy of training, resulting in a
      similar improvement in clinical results.

PMID- 16802270
TI  - Playing games: doctors and nurses and musical chairs.

PMID- 16802271
TI  - Autofluorescence imaging and narrow-band imaging for the detection of early
      neoplasia in patients with Barrett's esophagus.
AB  - High-resolution endoscopy (HRE), magnifying endoscopy, auto-fluorescence
      endoscopy, and narrow-band imaging (NBI) are promising techniques that could
      improve the detection of early neoplasia and the efficacy of endoscopic
      surveillance in patients with Barrett's esophagus. HRE improves the detection of
      lesions by white light, and video autofluorescence imaging (AFI) may have
      additional value in terms of sensitivity. The strengths ofAFI are its high
      sensitivity and a high negative predictive value,while potential limitations are
      its moderate specificity and positive predictive value. NBI enhances the mucosal
      and vascular patterns (i. e. the mucosal morphology) without the need for
      chromoendoscopy. The mucosal morphology features may be used to distinguish early
      neoplasia from nondysplastic Barrett's esophagus. Magnification is required for
      optimal use of NBI,which is a limitation of this technique. NBI with magnifying
      endoscopy could, however, be used for targeted inspection of lesions detected
      first by HRE or AFI. This approach has been shown to reduce the false-positive
      rate associated with AFI while maintaining its high sensitivity. To date, AFI and
      NBI have been used separately in two different prototypes, but a prototype
      endoscope that incorporates all of these techniques has recently become
      available. It is expected that future refinement of the autofluorescence and
      narrow-band modules may further increase their diagnostic value and ultimately
      improve the effectiveness of surveillance of Barrett's esophagus.

PMID- 16802272
TI  - Endoscopic transgastric debridement and drainage for splenic necrosis following
      an acute episode in chronic alcoholic pancreatitis.
AB  - Management of the complications and sequelae of acute and chronic pancreatitis is
      a clinical challenge. We report a case of successful transgastric drainage of
      splenic necrosis after occlusion of the splenic vessels during an acute episode
      in chronic pancreatitis.

PMID- 16802273
TI  - Long-Segment early squamous cell carcinoma of the proximal esophagus: curative
      treatment and long-term follow-up after 5-aminolevulinic acid (5-ALA)
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) is an established treatment for the ablation of
      dysplastic Barrett's epithelium and early esophageal carcinoma, but no data have
      been published on curative 5-aminolevulinic acid (5-ALA)-PDT for long-segment
      early esophageal cancer with infiltration of the upper sphincter. We describe
      successful curative treatment of an unusual early long-segment squamous cell
      carcinoma (uT1a,N0) of the proximal esophagus (18 - 28 cm aborally), with three
      sessions of 5-ALA-PDT. Endoscopic and endosonographic follow-up macroscopically
      showed a complete remission of the tumor, proven by biopsy showing total
      histological ablation. After a follow-up period of 23 months, there has been no
      indication of tumor recurrence. Early superficial (< 3 mm) squamous cell
      carcinomas of the esophagus can be ablated completely by 5-ALA-PDT. However, long
      term follow-up is required in order to prove the effectiveness of endoscopic
      ablation therapy for early esophageal cancer.

PMID- 16802274
TI  - Endoscopic resection of large colonic lipomas assisted by a prototype single-use
      Endoloop device.
AB  - Colonic lipomas are benign adipose tumors that occasionally cause symptoms.
      Endoscopic resection of large lipomas may be associated with the risk of
      hemorrhage or perforation. Experience with endoscopic resection of colonic
      lipomas with the assistance of a prototype single-use ligating Endoloop device,
      with a detachable snare unit, has not been previously reported. Three patients
      with a total of four large symptomatic colonic lipomas successfully underwent
      endoscopic resection with the aid of this device. One patient had self-limiting
      minor rectal bleeding which settled without consequence. All patients were well
      on follow-up, with resolution of their symptoms. This novel endoscopic technique
      should be considered during resection of large lipomas (> 10 mm diameter) to
      reduce the potential risk of bleeding.

PMID- 16802275
TI  - Endoscopic band ligation for Dieulafoy lesions: disadvantages and risks.

PMID- 16802276
TI  - The prevalence of esophageal cardiac glands: relationship with erosive
      esophagitis and nonerosive reflux disease (NERD) in Japanese patients.

PMID- 16802277
TI  - Retrograde endoscopic delivery of botulinum toxin for anal fissures.

PMID- 16802278
TI  - Multiple esophageal papillomas: a unique image.

PMID- 16802279
TI  - A tiered model of psychogeriatric service delivery: an evidence-based approach.
AB  - BACKGROUND: Previous models of mental health care for older persons have not
      considered the full spectrum of mental disorders. AIM: To describe a tiered model
      for comprehensive evidence-based planning of service delivery for mental
      disorders in late life. METHOD: The model depicts tiers of mental disorders in
      ascending order of severity and consequent interventions required. RESULTS:
      Interventions aim both to avert individuals from moving up tiers (prevention) and
      to move individuals down tiers (treatment). Individuals in the lower tiers have
      no mental disorders and prevention strategies are targeted at known risk factors.
      In the middle tiers, individuals with mild-moderate mental disorders will mainly
      be treated in primary care, often in collaboration with specialist mental health
      services for older people. Individuals in the top tiers with severe mental
      disorders usually require institutional care. CONCLUSION: The tiered model
      provides a basis for planning comprehensive service delivery.

PMID- 16802280
TI  - Lay perceptions regarding the competence of persons with Alzheimer's disease.
AB  - OBJECTIVE: The aim of the present study was to assess lay persons' perceptions
      about the competence of a person with AD and its relationship to social distance.
      METHODS: Face-to-face interviews were conducted with a total of 206 Jewish
      Israeli adults (mean age = 59.7) using an experimental vignette methodology,
      varying in the severity of the disease. Participants were requested to rate the
      competence of the person described in the vignette in the areas of driving,
      health-decision making, financial decisions, and the performance of instrumental
      activities of daily living. RESULTS: Results of the study showed that lay persons
      are able to make a distinction between different types of competence, and that
      their perceptions about competence affect greatly their behavioral discrimination
      toward a person with AD. CONCLUSIONS: Findings of this study stress the
      importance of clarifying the concept of competence among the lay public, in order
      to reduce the stigmatization of persons with Alzheimer's disease.

PMID- 16802281
TI  - Personality and behaviour changes mark the early stages of Alzheimer's disease in
      adults with Down's syndrome: findings from a prospective population-based study.
AB  - BACKGROUND: Research based on retrospective reports by carers suggests that the
      presentation of dementia in people with Down's syndrome may differ from that
      typical of Alzheimer's disease (AD) in the general population, with the earliest
      changes tending to be in personality or behaviour rather than in memory. This is
      the first long-term prospective study to test the hypothesis that such changes,
      which are more typical of dementia of frontal type (DFT) in the general
      population, mark the preclinical stage of AD in DS. METHODS: A previously
      identified population sample of older people with DS, first assessed in 1994 and
      followed-up 18 months later, were reassessed after a further 5 years. This study
      focuses on the 55 individuals who took part in the second follow-up. Dementia
      diagnosis was made using the modified CAMDEX informant interview and
      neuropsychological assessment was undertaken using the CAMCOG. Progression in
      clinical presentation was examined and degree of cognitive decline over time (on
      the CAMCOG and derived measures of executive function (EF) and memory) was
      compared across groups based on diagnosis and age: AD, DFT, personality/behaviour
      changes insufficient for a diagnosis of DFT (PBC), no diagnosis <50 years and no
      diagnosis 50 + years. RESULTS: Progression was observed from early changes in
      personality and behaviour to an increase in characteristics associated with
      frontal lobe dysfunction and/or a deterioration in memory, prior to the
      development of full AD. Individuals who met criteria for DFT were significantly
      more likely to progress to a diagnosis of AD over the following 5 years than
      those who did not and those with PBC were significantly more likely to progress
      to a more severe diagnosis (DFT or AD) than those without. In the 5 years prior
      to diagnosis, participants with PBC and DFT had shown a degree of global
      cognitive decline intermediate between those with no dementia and those with AD.
      Both these groups had shown a significant decline in EF but not in memory, while
      the AD group had shown significant decline on both measures, with a significantly
      greater degree of decline in memory. Older participants without informant
      reported changes showed a more generalised pattern of decline. CONCLUSIONS: These
      findings confirm that the early presentation of AD in DS is characterized by
      prominent personality and behaviour changes, associated with executive
      dysfunction, providing support for the notion that the functions of the frontal
      lobes may be compromised early in the course of the disease in this population.
      This has important implications for the diagnosis, treatment and management of
      dementia in people with DS.

PMID- 16802282
TI  - Validation analysis of informant's ratings of cognitive function in African
      Americans and Nigerians.
AB  - OBJECTIVES: To examine informant validity using the Community Screening Interview
      for Dementia (CSI 'D') both cross-sectionally and longitudinally in two very
      different cultures and to explore the effects of informants and study
      participants' characteristics on the validity of informants' reports. METHODS:
      Elderly African Americans age 65 years and older residing in Indianapolis, USA
      and elderly Yoruba Nigerians age 65 years and older residing in Ibadan, Nigeria
      were assessed on cognitive functioning using the CSI 'D' at baseline (1992-1993)
      and five-year follow-up (1997-1998). At baseline, the informant validity in both
      samples was evaluated against participants' cognitive tests using Pearson
      correlation and regular regression models. At follow-up, informants ratings on
      cognitive decline were assessed against participants' cognitive decline scores
      from baseline to follow-up using biserial correlation and logistic regressions.
      RESULTS: At baseline, informants' reports on cognitive functioning significantly
      correlated with cognitive scores in both samples (Indianapolis:r = -0.43, p <
      0.001; Ibadan:r = -0.47, p < 0.001). The participant-informant relationships
      significantly affected the informants' reports in the two samples with different
      patterns (p = 0.005 for Indianapolis and p < 0.001 for Ibadan) at a given level
      of cognitive functioning. African Americans spouses reported more cognitive
      problems, while siblings reported more problems for the Yoruba Nigerians. At
      follow-up, informants' ratings on cognitive decline significantly correlated with
      the cognitive decline scores (Indianapolis r = 0.38, p < 0.001; Ibadan r = 0.32,
      p < 0.001). The characteristics of study participants and informants had little
      impact on the informants' ratings on cognitive decline. CONCLUSIONS: Informant
      reports are valid in assessing the cognitive functioning of study participants
      both cross-sectionally and longitudinally in two very different cultures,
      languages and environments.

PMID- 16802283
TI  - Cerebral amyloid angiopathy and cortical microinfarcts as putative substrates of
      vascular dementia.
AB  - BACKGROUND AND PURPOSE: Vascular dementia (VaD) has occasionally been associated
      with cerebral amyloid angiopathy (CAA), but the prevalence and significance of
      this counterintuitive relationship are poorly known. Therefore, we investigated
      the presence and characteristics of CAA in brains of VaD cases. METHODS: We
      examined temporal and parietal regions of the cerebral cortex of 26 consecutive
      VaD cases from the Lund Longitudinal Dementia Study. We carried out
      immunohistochemistry and routine stainings, determined Apolipoprotein E (ApoE)
      genotypes, and obtained clinical characteristics on the studied group for
      retrospective analysis. RESULTS: CAA was marked in eight out of 26 cases, and
      correlated strongly with the presence of cortical microinfarcts, both in the
      temporal lobe and in the parietal lobe. Based on comparisons with eight age
      matched VaD cases without CAA, the clinical records suggested that VaD cases with
      CAA as a group exhibited less pronounced neurological symptoms. A clear
      contribution of the ApoE genotype could not be identified. CONCLUSIONS: Based on
      a combination of the clinical and pathological data, we suggest that
      microinfarcts in the cerebral cortex associated with severe CAA may be the
      primary pathological substrate in a significant proportion of VaD cases. Future
      studies should be undertaken to confirm or dismiss the hypothesis that these
      cases exhibit a different symptom profile than VaD cases without CAA.

PMID- 16802285
TI  - The neurobiology of neurooncology.
AB  - The histological classification of brain tumors currently is based on the
      morphological appearance and protein expression patterns that reflect specific
      cell types within the central nervous system. Recent studies have suggested that
      the cells of origin for brain tumors may persist in the fully formed tumors, and
      that these "cancer stem cells" might represent the relevant cellular targets for
      anticancer therapy. In this regard, insights into the developmental neurobiology
      of brain tumors has significant impact on our understanding of the molecular and
      cellular pathogenesis of these devastating cancers, as well as the development of
      new strategies for treating brain tumors.

PMID- 16802286
TI  - Progressive spinal axonal degeneration and slowness in ALS2-deficient mice.
AB  - OBJECTIVE: Homozygous mutation in the ALS2 gene and the resulting loss of the
      guanine exchange factor activity of the ALS2 protein is causative for autosomal
      recessive early-onset motor neuron disease that is thought to predominantly
      affect upper motor neurons. The goal of this study was to elucidate how the motor
      system is affected by the deletion of ALS2. METHODS: ALS2-deficient mice were
      generated by gene targeting. Motor function and upper and lower motor neuron
      pathology were examined in ALS2-deficient mice and in mutant superoxide dismutase
      1 (SOD1) mice that develop ALS-like disease from expression of an ALS-linked
      mutation in SOD1. RESULTS: ALS2-deficient mice demonstrated progressive axonal
      degeneration in the lateral spinal cord that is also prominent in mutant SOD1
      mice. Despite the vulnerability of these spinal axons, lower motor neurons in
      ALS2-deficient mice were preserved. Behavioral studies demonstrated slowed
      movement without muscle weakness in ALS2(-/-) mice, consistent with upper motor
      neuron defects that lead to spasticity in humans. INTERPRETATION: The combined
      evidence from mice and humans shows that deficiency in ALS2 causes an upper motor
      neuron disease that in humans closely resembles a severe form of hereditary
      spastic paralysis, and that is quite distinct from amyotrophic lateral sclerosis.

PMID- 16802287
TI  - Patient treatment preferences in localized prostate carcinoma: The influence of
      emotion, misconception, and anecdote.
AB  - BACKGROUND: Multiple therapeutic options exist for localized prostate carcinoma,
      without conclusive evidence to guide the choice of treatment. Thus, treatment
      should reflect trade-offs between the probability of curing disease and the
      desire to avoid treatment-associated side effects. Factors that actually
      influence patient treatment preferences are poorly understood. METHODS: We
      reviewed medical records and carried out in-depth, semistructured interviews of
      20 men with newly-diagnosed, clinically-localized prostate carcinoma in a
      Veterans Affairs Hospital following their first consultations with urologists and
      before treatments were initiated. Six to eight months after treatment, we carried
      out follow-up interviews. Interviews explored beliefs and attitudes about
      prostate cancer and treatment options, emotional reactions to the diagnosis,
      treatment preferences, information sources, and perceptions of interactions with
      urologists. RESULTS: Patient treatment preferences were not based on careful
      assessments of numerical risks for various clinical outcomes. Instead, feelings
      of fear and uncertainty contributed to a desire for rapid treatment, and specific
      preferences were profoundly influenced by misconceptions, especially about
      prostatectomy, and by anecdotes about the experiences of others with cancer. Few
      patients wanted to seek second opinions. Most patients received treatments that
      matched their initial preferences. Afterwards, they justified their choices in
      terms of the same misconceptions and anecdotal influences invoked during
      treatment deliberation. CONCLUSIONS: For men with localized prostate carcinoma,
      the treatment decision-making process would benefit from interventions that
      moderate feelings of fear and a desire for rapid treatment, dispel common and
      powerful misconceptions about prostate cancer and its therapies, and help
      patients avoid over-reliance on anecdotes.

PMID- 16802288
TI  - Influence of obesity on biochemical and clinical failure after external-beam
      radiotherapy for localized prostate cancer.
AB  - BACKGROUND: Several reports have shown that obesity is associated with increased
      risk of biochemical failure after radical prostatectomy. However, limited
      information is available regarding the impact of obesity on prostate cancer
      progression after radiotherapy. The current study sought to determine whether
      obesity was an independent predictor of biochemical failure (BF) and clinical
      recurrence (CF) among patients treated with external-beam radiotherapy (EBRT).
      METHODS: A retrospective analysis was performed on 873 patients receiving EBRT as
      the sole treatment for localized prostate cancer between 1988 and 2001. The
      Kaplan-Meier method, log-rank test, and Cox proportional hazards analyses were
      performed. RESULTS: Of the 873 patients, 18% were mildly obese and 5% were
      moderately to severely obese. Obesity was related to younger age at diagnosis (P
      < .001), more recent year of diagnosis (P = .03), and race (P = .03), with
      African-American men having the highest obesity rates. During a mean follow-up of
      96 months, 295 patients experienced BF and 127 had CF. On multivariate analysis,
      controlling for clinical and treatment characteristics, increased body mass index
      (BMI) significantly predicted BF (hazards ratio [HR] = 1.04; 95% confidence
      interval [95% CI], 1.02-1.07) with a positive trend by BMI category (P = .001).
      Similar results were found when the outcome was CF; BMI remained an independent
      predictor of progression (HR = 1.05; 95% CI, 1.01-1.09), with a statistically
      significant trend by increased BMI category (P = .03). CONCLUSIONS: The current
      findings validate the important role of obesity, not only on BF but also on CF,
      and suggest a link to the biologic basis of tumor progression that can be
      therapeutically exploited.

PMID- 16802289
TI  - Mobile phone emissions and human brain excitability.
AB  - OBJECTIVE: To test-via Transcranial Magnetic Stimulation (TMS)-the excitability
      of each brain hemisphere after 'real' or 'sham' exposure to the electromagnetic
      field (EMF) generated by a mobile phone operating in the Global System for Mobile
      Communication (GSM). METHODS: Fifteen male volunteers attended two experimental
      sessions, one week apart, in a cross-over, double-blind paradigm. In one session
      the signal was turned ON (EMF-on, real exposure), in the other it was turned OFF
      (EMF-off, sham exposure), for 45 minutes. Motor Evoked Potentials (MEPs) were
      recorded using a paired-pulse paradigm (testing intracortical excitability with 1
      to 17 ms interstimulus intervals), both before and at different times after
      exposure to the EMF. Short Intracortical Inhibition (SICI) and Facilitation (ICF)
      curves were evaluated both on the exposed and non-exposed hemispheres. Tympanic
      temperature was collected during each session. RESULTS: The intracortical
      excitability curve becomes significantly modified during real exposure, with SICI
      being reduced and ICF enhanced in the acutely exposed brain hemisphere as
      compared to the contralateral, non-exposed hemisphere or to sham exposure.
      Tympanic temperature showed no significant main effect or interactions.
      INTERPRETATION: These results demonstrate that GSM-EMFs modify brain
      excitability. Possible implications and applications are discussed.

PMID- 16802290
TI  - Pesticide exposure and risk for Parkinson's disease.
AB  - OBJECTIVE: Chronic, low-dose exposure to pesticides is suspected to increase the
      risk for Parkinson's disease (PD), but data are inconclusive. METHODS: We
      prospectively examined whether individuals exposed to pesticides have higher risk
      for PD than those not exposed. The study population comprised participants in the
      Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation of US
      men and women initiated in 1992 by the American Cancer Society. Follow-up surveys
      were conducted in 1997, 1999, and 2001. The 143,325 individuals who returned the
      2001 survey and did not have a diagnosis or symptoms of PD at baseline (1992)
      were included in the analyses. RESULTS: Exposure to pesticides was reported by
      7,864 participants (5.7%), including 1,956 farmers, ranchers, or fishermen.
      Individuals exposed to pesticides had a 70% higher incidence of PD than those not
      exposed (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.3; p =
      0.002). The relative risk for pesticide exposure was similar in farmers and
      nonfarmers. No relation was found between risk for PD and exposure to asbestos,
      chemical/acids/solvents, coal or stone dust, or eight other occupational
      exposures. INTERPRETATION: These data support the hypothesis that exposure to
      pesticides may increase risk for PD. Future studies should seek to identify the
      specific chemicals responsible for this association.

PMID- 16802291
TI  - Trial of celecoxib in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To determine whether chronic treatment with celecoxib, a
      cyclooxygenase-2 inhibitor that has been shown to be beneficial in preclinical
      testing, is safe and effective in amyotrophic lateral sclerosis (ALS). METHODS: A
      double-blind, placebo-controlled, clinical trial was conducted. Three hundred
      research subjects with ALS were randomized (2:1) to receive celecoxib (800
      mg/day) or placebo for 12 months. The primary outcome measure was the rate of
      change in upper extremity motor function measured by the maximum voluntary
      isometric contraction strength. Secondary end points included safety, survival,
      change in cerebrospinal fluid prostaglandin E(2) levels, and changes in the rate
      of decline of leg and grip strength, vital capacity, ALS Functional Rating Scale
      Revised, and motor unit number estimates. RESULTS: Celecoxib did not slow the
      decline in muscle strength, vital capacity, motor unit number estimates, ALS
      Functional Rating Scale-Revised, or affect survival. Celecoxib was well tolerated
      and was not associated with an increased frequency of adverse events.
      Prostaglandin E(2) levels in cerebrospinal fluid were not elevated at baseline
      and did not decline with treatment. INTERPRETATION: At the dosage studied,
      celecoxib did not have a beneficial effect on research subjects with ALS, and it
      was safe. A biological effect of celecoxib was not demonstrated in the
      cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg/day in
      ALS are not warranted.

PMID- 16802292
TI  - Alsin/Rac1 signaling controls survival and growth of spinal motoneurons.
AB  - OBJECTIVE: Recessive mutations in alsin, a guanine-nucleotide exchange factor for
      the GTPases Rab5 and Rac1, cause juvenile amyotrophic lateral sclerosis (ALS2)
      and related motoneuron disorders. Alsin function in motoneurons remained unclear
      because alsin knock-out mice do not develop overt signs of motoneuron
      degeneration. METHODS: To generate an alsin loss-of-function model in an ALS
      relevant cell type, we developed a new small interfering RNA electroporation
      technique that allows efficient knock down of alsin in embryonic rat spinal
      motoneurons. RESULTS: After small interfering RNA-mediated alsin knockdown,
      cultured motoneurons displayed a reduced apparent size of EEA1-labeled early
      endosomes and an increased intracellular accumulation of transferrin and L1CAM.
      Alsin knockdown induced cell death in 32 to 48% of motoneurons and significantly
      inhibited axon growth in the surviving neurons. Both cellular phenotypes were
      mimicked by expression of a dominant-negative Rac1 mutant and were completely
      blocked by expression of a constitutively active Rac1 mutant. Expression of
      dominant-negative or constitutively active forms of Rab5 had no such effects.
      INTERPRETATION: Our data demonstrate that alsin controls the growth and survival
      of motoneurons in a Rac1-dependant manner. The strategy reported here illustrates
      how small interfering RNA electroporation can be used to generate cellular models
      of neurodegenerative disease involving a loss-of-function mechanism.

PMID- 16802293
TI  - How to successfully apply animal studies in experimental allergic
      encephalomyelitis to research on multiple sclerosis.
AB  - In their Point of View entitled "Experimental Allergic Encephalomyelitis: A
      Misleading Model of Multiple Sclerosis," Sriram and Steiner(1) wrote, "The most
      disappointing aspect of EAE [experimental allergic encephalomyelitis] as a
      potential model for MS is its almost total inability to point toward a meaningful
      therapy or therapeutic approach for MS." Actually, EAE has led directly to the
      development of three therapies approved for use in multiple sclerosis (MS):
      glatiramer acetate, mitoxantrone, and natalizumab. Several new approaches to MS
      are in clinical trials based on positive indications in preclinical work relying
      on EAE. New clues to the pathogenesis of MS and new potential surrogate markers
      for MS are shown from research involving EAE when it is critically coupled with
      actual findings in MS. There are pitfalls in overreliance on the EAE model, or on
      any animal model for any human disease. Nevertheless, over the past 73 years, the
      EAE model has proved itself remarkably useful for aiding research on MS.

PMID- 16802294
TI  - Amyloid load and cerebral atrophy in Alzheimer's disease: an 11C-PIB positron
      emission tomography study.
AB  - To determine the relationship between cerebral amyloid plaque load and rates of
      cerebral atrophy in Alzheimer's disease. (11)C-PIB((11)C-6-OH benzothiazole)PET
      (positron emission tomography) findings were correlated with volumetric magnetic
      resonance imaging (MRI) measurements in nine subjects with mild to moderate AD.
      Analysis revealed a positive correlation between rates of whole brain atrophy and
      whole brain (p = 0.019) and regional (11)C-PIB uptake. This provides support for
      the central role of amyloid deposition in the pathogenesis of AD.

PMID- 16802295
TI  - Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension.
AB  - To report two unrelated patients with a new phenotype of nonketotic
      hyperglycinemia associated with idiopathic pulmonary hypertension. Clinical
      findings included rapidly progressive neurological deterioration with onset in
      the first year of life characterized by developmental regression without seizures
      or electroencephalogram abnormalities during follow-up. Both patients died before
      the age of 18 months. Glycine cleavage system deficiency was confirmed by
      enzymatic studies in frozen liver. Molecular analysis in the related genes showed
      no pathogenic mutation. Radiological and pathological findings were consistent
      with progressive vacuolating encephalopathy. Our patients with biochemical and
      enzymatic parameters consistent with atypical nonketotic hyperglycinemia. The
      clinical and radiological evolution, as progressive vacuolating
      leukoencephalopathy and the association with pulmonary hypertension constitute a
      previously unrecognized variant.

PMID- 16802296
TI  - Follow-up of four narcolepsy patients treated with intravenous immunoglobulins.

PMID- 16802299
TI  - Recovery from paralysis in adult rats using embryonic stem cells.
AB  - OBJECTIVE: We explored the potential of embryonic stem cell-derived motor neurons
      to functionally replace those cells destroyed in paralyzed adult rats. METHODS:
      We administered a phosphodiesterase type 4 inhibitor and dibutyryl cyclic
      adenosine monophosphate to overcome myelin-mediated repulsion and provided glial
      cell-derived neurotrophic factor within the sciatic nerve to attract transplanted
      embryonic stem cell-derived axons toward skeletal muscle targets. RESULTS: We
      found that these strategies significantly increased the success of transplanted
      axons extending out of the spinal cord into ventral roots. Furthermore,
      transplant-derived axons reached muscle, formed neuromuscular junctions, were
      physiologically active, and mediated partial recovery from paralysis.
      INTERPRETATION: We conclude that restoration of functional motor units by
      embryonic stem cells is possible and represents a potential therapeutic strategy
      for patients with paralysis. To our knowledge, this is the first report of the
      anatomical and functional replacement of a motor neuron circuit within the adult
      mammalian host.

PMID- 16802300
TI  - Basic and clinical research: what is the most appropriate weighting in a public
      investment portfolio?

PMID- 16802301
TI  - Statins and the blood-brain barrier: plugging the holes.

PMID- 16802302
TI  - Cognitive prognosis in chronic temporal lobe epilepsy.
AB  - OBJECTIVE: First, to determine whether patients with chronic temporal lobe
      epilepsy have a different cognitive trajectory compared to control subjects over
      a prospective 4-year interval; second, to determine the proportion of patients
      who exhibit abnormal cognitive change and their profile of demographic, clinical
      epilepsy, and baseline quantitative magnetic resonance imaging characteristics;
      and third, to determine the most vulnerable cognitive domains. METHODS:
      Participants with chronic temporal lobe epilepsy (n = 46) attending a tertiary
      referral clinic and healthy control subjects (n = 65) underwent
      neuropsychological assessment and reevaluation 4 years later. Analysis of test
      retest patterns identified individual patients with adverse cognition outcomes.
      RESULTS: The prospective cognitive trajectory of patients with chronic temporal
      lobe epilepsy differs from age- and sex-matched healthy control subjects. Lack of
      practice effects is common, but frank adverse cognitive outcomes are observed in
      a subset of patients (20-25%), particularly in vulnerable cognitive domains that
      include memory. Cognitive declines are associated with a profile of abnormalities
      in baseline quantitative magnetic resonance volumetrics, lower baseline
      intellectual capacity, as well as longer duration of epilepsy and older
      chronological age. INTERPRETATION: Cognitive prognosis is poor for a subset of
      patients characterized by chronicity of epilepsy, older age, lower intellectual
      ability, and more baseline abnormalities in quantitative magnetic resonance
      volumetrics.

PMID- 16802303
TI  - N-methylation of N(alpha)-acylated, fully C(alpha)-methylated, linear, folded
      peptides: synthetic and conformational aspects.
AB  - Peptides characterized by single or multiple N-methylated, C(alpha)
      trisubstituted (e.g., protein) amino acids are of great interest in medicinal
      chemistry. Several naturally occurring peptides, remarkably stable to enzymatic
      attacks, are based on N-methylated residues. The classical conditions
      (CH(3)I/Ag(2)O in DMF, 24 h, room temperature) for N-methylation of the peptide
      function are useful tools for distinguishing solvent exposed from
      intramolecularly H-bonded -CO-NH- groups in peptides. In this work we have
      extended this reaction to N(alpha)-acylated, linear peptides based exclusively on
      helicogenic C(alpha)-tetrasubstituted alpha-amino acids, e.g., Aib (alpha
      aminoisobutyric acid) or (alphaMe)Nva (C(alpha)-methyl norvaline) residues. Under
      the experimental conditions used, only amide monomethylation (on the N-terminal,
      acylated, residue) takes place. Methylation of internal peptide groups linking
      two C(alpha)-tetrasubstituted residues was not observed. Our FT-IR absorption,
      NMR, and X-ray diffraction investigations support the view that the beta-turn and
      3(10)-helical conformations preferred by the original peptides are not
      dramatically perturbed in the derivatives monomethylated at position 1. In
      particular, the tertiary amide bonds are trans. Conversely, the packing modes in
      the crystals are strongly influenced by the reduction of the number of H-bonding
      donors. The MeXxx-Xxx peptide bond is readily disrupted under mild acidic
      conditions.

PMID- 16802304
TI  - Solvent-induced lysozyme gels: effects of system composition and temperature on
      structural and dynamic characteristics.
AB  - The gelation process of lysozyme in water/tetramethylurea in the presence of salt
      was investigated as a function of temperature and system composition by rheology,
      infrared spectroscopy, and microcalorimetry. Times and temperatures of gelation
      were determined from the variation of the storage (G') and loss (G'') moduli. It
      was found that gelation times follow exponential decays with both protein and
      tetramethylurea (TMU) concentrations and with temperature. The activation energy
      for the overall process shows a linear dependence on TMU mass fraction. A
      strongly increased beta-sheet content and reduced alpha-helix occur with the
      increase of TMU concentration in the binary solvent. Also, a linear decrease of
      lysozyme denaturation temperature and enthalpy on TMU concentration is found for
      the TMU mass fraction up to 0.5, above which no denaturation signal can be
      detected.

PMID- 16802306
TI  - Promoting the skills of knowledge translation in an online master of science
      course in primary health care.
AB  - We present 4 key arguments: (1) knowledge translation requires tacit and explicit
      knowledge that must be introduced into the organization as well as simply
      acquired by individuals; (2) educating for knowledge translation must go beyond
      conveying facts and developing capability; (3) a constructivist and collaborative
      approach to education can address the needs of learners for knowledge
      translation; and (4) the online environment, if appropriately used, has many
      useful features for supporting constructivist and collaborative learning. We
      illustrate these arguments with reference to a part-time online master of science
      course whose learners are mostly senior health care professionals engaged in
      knowledge translation.

PMID- 16802307
TI  - Facilitating interpersonal interaction and learning online: linking theory and
      practice.
AB  - INTRODUCTION: An earlier study of physicians' perceptions of interactive online
      learning showed that these were shaped both by program design and quality and the
      quality and quantity of interpersonal interaction. We explore instructor roles in
      enhancing online learning through interpersonal interaction and the learning
      theories that inform these. METHODS: This was a qualitative study using focus
      groups and interviews. Using purposive sampling, 50 physicians were recruited
      based on their experience with interactive online CME and face-to-face CME.
      Qualitative thematic and interpretive analysis was used. RESULTS: Two
      facilitation roles appeared key: creating a comfortable learning environment and
      enhancing the educational value of electronic discussions. Comfort developed
      gradually, and specific interventions like facilitating introductions and sharing
      experiences in a friendly, informative manner were helpful. As in facilitating
      effective small-group learning, instructors' thoughtful use of techniques that
      facilitated constructive interaction based on learner's needs and practice
      demands contributed to the educational value of interpersonal interactions.
      DISCUSSION: Facilitators require enhanced skills to engage learners in meaningful
      interaction and to overcome the transactional distance of online learning. The
      use of learning theories, including behavioral, cognitive, social, humanistic,
      and constructivist, can strengthen the educational design and facilitation of
      online programs. Preparation for online facilitation should include instruction
      in the roles and techniques required and the theories that inform them.

PMID- 16802308
TI  - Organizational change in management of hepatitis C: evaluation of a CME program.
AB  - INTRODUCTION: Effective treatment regimens exist for the hepatitis C virus (HCV);
      however, clinicians are often resistant to evaluation or treatment of patients
      with alcohol or substance abuse problems. We describe a continuing medical
      education (CME) program for clinicians in a nationwide health care system, with
      emphasis on current treatment practices, multispecialty collaboration, and
      organizational change. METHODS: Quantitative measures were used to assess changes
      in knowledge and treatment confidence, and site-specific organizational changes
      were qualitatively evaluated. The CME program included a preassessment of current
      HCV knowledge and care; a 2-day preceptorship; and follow-up with coaching calls
      at 1, 3, and 6 months. Program attendees included 54 medical and mental health
      providers from 28 Veterans Affairs Medical Centers. RESULTS: Knowledge following
      the CME program increased significantly. In 93% of the sites, there were
      organizational changes such as HCV support group-initiated group education, in
      service training, improvement in patient notification or scheduling processes,
      hiring of new clinical staff, development of a business plans, and discussions
      about changes with administration. Of all sites, 15 (54%) changed existing
      antiviral treatment protocols, 18 (64%) established collaborative relationships,
      and almost half (13/28) established regular use of depression and alcohol use
      screening tools. Major barriers to change included lack of administrative support
      or resources (or both) and difficulty collaborating with mental health
      colleagues. DISCUSSION: This multifaceted CME program with follow-up coaching
      calls significantly increased individual knowledge and confidence scores and
      resulted in improved clinic processes and structures. Organizational change was
      facilitated by the development of an action plan. The major change agent was a
      nurse; the primary deterrent was an administrator.

PMID- 16802310
TI  - Exploring relationships of knowledge to action.

PMID- 16802312
TI  - Promoting physicians' self-assessment and quality improvement: the ABIM diabetes
      practice improvement module.
AB  - INTRODUCTION: The American Board of Internal Medicine (ABIM) recognized that
      certification and recertification must be based on an assessment of performance
      in practice as well as an examination of medical knowledge. Physician self
      assessment of practice performance is proposed as one method that certification
      boards may use to evaluate competence in practice-based learning and improvement
      and systems-based practice. METHODS: Sixteen practicing general internists and
      endocrinologists with 10-year time-limited certification participated in a beta
      test of the ABIM's diabetes practice improvement module (PIM) as part of their
      recertification program. A PIM consists of a self-directed medical record audit,
      practice system survey, and patient survey. A quality improvement education
      specialist from the Connecticut Quality Improvement Organization provided on-site
      and distance consultation on quality improvement methods and tools. An
      independent audit assessed the reliability of physician self-audit. Qualitative
      interviews were conducted at 2 time points to assess for physician satisfaction
      and behavioral change in quality improvement. RESULTS: Fourteen physicians
      completed the diabetes PIM. All but 1 physician found the medical record audit to
      provide important information about the practice. Of the 11 physicians who
      completed a follow-up interview, 10 stated that the quality improvement education
      specialist helped improve their practice. DISCUSSION: Self-assessment using the
      ABIM diabetes PIM as part of recertification provides valuable practice
      information and can lead to meaningful behavioral change by physicians.
      Collaboration with an educator in quality improvement appears to facilitate the
      effects of the practice improvement module. Future work should investigate the
      effect on patient outcomes.

PMID- 16802313
TI  - Information-seeking behaviors and reflective practice.
AB  - INTRODUCTION: As they care for patients, physicians raise questions, but they
      pursue only a portion of them. Without the best information and evidence, care
      and patient safety may be compromised. Understanding when and why problems prompt
      physicians to look for information and integrate results into their knowledge
      base is critical and shapes one part of reflection about care. This study
      explores the role of the Internet in gathering medical information as one step in
      that reflective practice, the barriers to its use, and changes in utilization
      over time. METHODS: A questionnaire with 18 items adapted from previous studies
      was sent by facsimile to a randomly selected sample of U.S. physicians in all
      specialties and active in practice. RESULTS: Specific patient problems and latest
      research in a specific topic most often prompt physicians to search on the
      Internet. Younger physicians and female physicians were most likely to seek
      information on a specific patient problem. Only 9% of all respondents (n = 2,500)
      searched for information during a patient encounter. When unsure about diagnostic
      and management issues for a complex case, 41.3% chose to consult with a colleague
      or read from a text (22.8%). Searching most often occurred at home after work
      (38.2%) or during breaks in the day (35.7%). Most (68.7%) found the information
      they were looking for more than 51% of the time. Searching was facilitated by
      knowing preferred sites and access in the clinical setting. The greatest barriers
      to answering clinical questions included a lack of specific information and too
      much information to scan. DISCUSSION: Although physicians are increasingly
      successful and confident in their Internet searching to answer questions raised
      in patient care, few choose to seek medical information during a patient
      encounter. Internet information access may facilitate overall reflection on
      practice; physicians do not yet use this access in a just-in-time manner for
      immediately solving difficult patient problems but instead continue to rely on
      consultation with colleagues. Professional association Web sites and point-of
      care databases are helpful. From physicians' use of the Internet, professionals
      in continuing medical education must learn which search engines and sites are
      trusted and preferred.

PMID- 16802314
TI  - Evaluation of an online bioterrorism continuing medical education course.
AB  - INTRODUCTION: Much of the international community has an increased awareness of
      potential biologic, chemical, and nuclear threats and the need for physicians to
      rapidly acquire new knowledge and skills in order to protect the public's health.
      The present study evaluated the educational effectiveness of an online
      bioterrorism continuing medical education (CME) activity designed to address
      clinical issues involving suspected bioterrorism and reporting procedures in the
      United States. METHODS: This was a retrospective survey of physicians who had
      completed an online CME activity on bioterrorism compared with a nonparticipant
      group who had completed at least 1 unrelated online CME course from the same
      medical school Web site and were matched on similar characteristics. An online
      survey instrument was developed to assess clinical and systems knowledge and
      confidence in recognition of illnesses associated with a potential bioterrorism
      attack. A power calculation indicated that a sample size of 100 (50 in each
      group) would achieve 90% power to detect a 10% to 15% difference in test scores
      between the two groups. RESULTS: Compared with nonparticipant physicians,
      participants correctly diagnosed anthrax (p = .01) and viral exanthem (p = .01),
      but not smallpox, more frequently than nonparticipants. Participants knew more
      frequently than nonparticipants who to contact regarding a potential bioterrorism
      event (p = .03) Participants were more confident than nonparticipants about
      finding information to guide diagnoses of patients with biologic exposure (p =
      .01), chemical exposure (p = .02), and radiation exposure (p = .04). DISCUSSION:
      An online bioterrorism course shows promise as an educational intervention in
      preparing physicians to better diagnose emerging rare infections, including those
      that may be associated with a bioterrorist event, in increasing confidence in
      diagnosing these infections, and in reporting of such infections for practicing
      physicians.

PMID- 16802315
TI  - What constitutes commercial bias compared with the personal opinion of experts?
AB  - INTRODUCTION: The presence of commercial messages in continuing medical education
      (CME) is an ongoing cause of concern. This study identifies actions perceived by
      CME participants to convey commercial bias from CME faculty. METHODS: A
      questionnaire listing actions associated with CME activities was distributed to
      230 randomly selected participants from 7 CME activities designated for AMA PRA
      Category 1 Credit. The activities were held over an 8-month period. Participants
      were asked to complete the questionnaire before participating in the live
      activity. RESULTS: Nine actions identified by over 50% of all respondents were
      perceived to convey commercial bias. The most critical ones reflecting commercial
      bias were speaking about only one agent, not providing a balanced presentation of
      all agents, and faculty relationships with commercial supporters. Ten actions
      identified by over 50% of the respondents were perceived to convey personal
      opinion of the faculty. The most prevalent actions were the influence of mentors
      or teachers, relating general practice habits from the faculty member's own
      experience, and cultural differences among patient populations. More than half
      the respondents who indicated they perceived commercial bias in certified
      activities attributed this perception to an overall impression, instead of 1 or 2
      specific actions. DISCUSSION: Actions were identified that conveyed differences
      between commercial messages and personal opinion. CME providers should define
      commercial bias for participants, faculty, and planners and provide education
      about that definition.

PMID- 16802316
TI  - Apparent diffusion coefficients from high angular resolution diffusion imaging:
      estimation and applications.
AB  - High angular resolution diffusion imaging has recently been of great interest in
      characterizing non-Gaussian diffusion processes. One important goal is to obtain
      more accurate fits of the apparent diffusion processes in these non-Gaussian
      regions, thus overcoming the limitations of classical diffusion tensor imaging.
      This paper presents an extensive study of high-order models for apparent
      diffusion coefficient estimation and illustrates some of their applications.
      Using a meaningful modified spherical harmonics basis to capture the physical
      constraints of the problem, a new regularization algorithm is proposed. The new
      smoothing term is based on the Laplace-Beltrami operator and its closed form
      implementation is used in the fitting procedure. Next, the linear transformation
      between the coefficients of a spherical harmonic series of order l and
      independent elements of a rank-l high-order diffusion tensor is explicitly
      derived. This relation allows comparison of the state-of-the-art anisotropy
      measures computed from spherical harmonics and tensor coefficients. Published
      results are reproduced accurately and it is also possible to recover voxels with
      isotropic, single fiber anisotropic, and multiple fiber anisotropic diffusion.
      Validation is performed on apparent diffusion coefficients from synthetic data,
      from a biological phantom, and from a human brain dataset.

PMID- 16802317
TI  - Rapid cardiac-output measurement with ungated spiral phase contrast.
AB  - An ungated spiral phase-contrast (USPC) method was used to measure cardiac output
      (CO) rapidly and conveniently. The USPC method, which was originally designed for
      small peripheral vessels, was modified to assess CO by measuring flow in the
      ascending aorta (AA). The modified USPC used a 12-interleaf spiral trajectory to
      acquire full-image data every 283 ms with 2-mm spatial resolution. The total scan
      time was 5 s. For comparison, a triggered real-time (TRT) method was used to
      indirectly calculate CO by measuring left-ventricular (LV) volume. The USPC and
      TRT measurements from all normal volunteers agreed. In a patient with patent
      ductus arteriosus (PDA), high CO was measured with USPC, which agreed well with
      the invasive cardiac-catheterized measurement. In normal volunteers, CO dropped
      about 20-30% with Valsalva maneuvering, and increased about 100% after exercise.
      Continuous 28-s cycling between Valsalva maneuvering and free-breathing showed
      that USPC can temporally resolve physiological CO changes.

PMID- 16802318
TI  - Defining the fold space of membrane proteins: the CAMPS database.
AB  - Recent progress in structure determination techniques has led to a significant
      growth in the number of known membrane protein structures, and the first
      structural genomics projects focusing on membrane proteins have been initiated,
      warranting an investigation of appropriate bioinformatics strategies for optimal
      structural target selection for these molecules. What determines a membrane
      protein fold? How many membrane structures need to be solved to provide
      sufficient structural coverage of the membrane protein sequence space? We present
      the CAMPS database (Computational Analysis of the Membrane Protein Space)
      containing almost 45,000 proteins with three or more predicted transmembrane
      helices (TMH) from 120 bacterial species. This large set of membrane proteins was
      subjected to single-linkage clustering using only sequence alignments covering at
      least 40% of the TMH present in a given family. This process yielded 266 sequence
      clusters with at least 15 members, roughly corresponding to membrane structural
      folds, sufficiently structurally homogeneous in terms of the variation of TMH
      number between individual sequences. These clusters were further subdivided into
      functionally homogeneous subclusters according to the COG (Clusters of
      Orthologous Groups) system as well as more stringently defined families sharing
      at least 30% identity. The CAMPS sequence clusters are thus designed to reflect
      three main levels of interest for structural genomics: fold, function, and
      modeling distance. We present a library of Hidden Markov Models (HMM) derived
      from sequence alignments of TMH at these three levels of sequence similarity.
      Given that 24 out of 266 clusters corresponding to membrane folds already have
      associated known structures, we estimate that 242 additional new structures, one
      for each remaining cluster, would provide structural coverage at the fold level
      of roughly 70% of prokaryotic membrane proteins belonging to the currently most
      populated families.

PMID- 16802319
TI  - The reaction mechanism of iron and manganese superoxide dismutases studied by
      theoretical calculations.
AB  - We have studied the detailed reaction mechanism of iron and manganese superoxide
      dismutase with density functional calculations on realistic active-site models,
      with large basis sets and including solvation, zero-point, and thermal effects.
      The results indicate that the conversion of O2- to O2 follows an associative
      mechanism, with O2- directly binding to the metal, followed by the protonation of
      the metal-bound hydroxide ion, and the dissociation of 3O2. All these reaction
      steps are exergonic. Likewise, we suggest that the conversion of O2- to H2O2
      follows an at least a partly second-sphere pathway. There are small differences
      in the preferred oxidation and spin states, as well as in the geometries, of Fe
      and Mn, but these differences have little influence on the energetics, and
      therefore on the reaction mechanism of the two types of superoxide dismutases.
      For example, the two metals have very similar reduction potentials in the active
      site models, although they differ by 0.7 V in water solution. The reaction
      mechanisms and spin states seem to have been designed to avoid spin conversions
      or to facilitate them by employing nearly degenerate spin states.

PMID- 16802320
TI  - Neurovascular and neuronal protection by E64d after focal cerebral ischemia in
      rats.
AB  - Calpains and cathepsins are two families of proteases that play an important role
      in ischemic cell death. In this study, we investigated the effect of E64d, a mu
      calpain and cathepsin B inhibitor, in the prevention of neuronal and endothelial
      apoptotic cell death after focal cerebral ischemia in rats. Rats underwent 2 hr
      of transient focal ischemia from middle cerebral artery occlusion (MCAO) and were
      sacrificed 24 hr later. E64d (5 mg/ kg intraperitoneally) was administered 30 min
      before MCAO. Assessment included neurological function, infarction volume, brain
      water content, blood-brain barrier permeability, histology, and
      immunohistochemistry. The E64d-treated rats had significant brain protection
      against ischemic damage. We observed a reduction of infarction volume, brain
      edema, and improved neurological scores in E64d-treated rats compared with the
      nontreated control. Furthermore, there was a remarkable reduction in both
      proteases and caspase-3 activation and apoptotic changes in both neurons and
      endothelial cells in E64d-treated rats. These results suggest that E64d protects
      the brain against ischemic/reperfusion injury by attenuating neuronal and
      endothelial apoptosis.

PMID- 16802321
TI  - PTEN, Akt, and GSK3beta signalling in rat primary cortical neuronal cultures
      following tumor necrosis factor-alpha and trans-4-hydroxy-2-nonenal treatments.
AB  - PTEN is a dual phosphatase that negatively regulates the phosphatidylinositol 3
      kinase (PI3K)/Akt signalling pathway important for cell survival. We determined
      effects of the inflammation and oxidative stresses of tumor necrosis factor-alpha
      (TNFalpha) and trans-4-hydroxy-2-nonenal (HNE), respectively, on PTEN, Akt, and
      GSK3beta signalling in rat primary cortical neurons. The inhibitors
      bisperoxovanadium [bpV(Pic)] and LY294002 were also used to determine PTEN and
      PI3K involvement in TNFalpha and HNE modulation of neuronal cell death. PTEN
      inhibition with bpV(Pic) alone did not affect Ser(473)Akt or Ser(9)GSK3beta
      phosphorylation. Instead, effects of this inhibitor were manifest when it was
      used together with TNFalpha and to a lesser extent with HNE. TNFalpha together
      with PTEN inhibition increased phosphorylation of Ser(473)Akt and Ser(9)GSK3beta.
      TNFalpha and HNE both gave decreased numbers of viable and increased numbers of
      early apoptotic neurons. PTEN inhibition partially reversed the toxic effect of
      TNFalpha as shown by an increased number of viable and a decreased number of
      early apoptotic neurons. All effects were reversed by PI3K inhibition. HNE
      together with inhibition of PTEN gave increased Ser(473)Akt but not
      Ser(9)GSK3beta phosphorylation and no effects on the number of viable or early
      apoptotic cells. In conclusion, PTEN inhibition gives a mild reversal of TNFalpha
      but not HNE-induced cell death via the PI3K pathway.

PMID- 16802322
TI  - Enhanced activation of Ca2+/calmodulin-dependent protein kinase II upon
      downregulation of cyclin-dependent kinase 5-p35.
AB  - Cyclin-dependent kinase 5 (Cdk5)-p35 is downregulated in cultured neurons by N
      methyl-D-aspartate (NMDA) via the proteasomal degradation of p35. However, it is
      not known where in neurons this downregulation occurs or the physiologic meaning
      of the reaction. We show the enrichment of Cdk5 and p35 in the postsynaptic
      density and the NMDA-induced degradation of postsynaptic p35 using brain slices
      and cultured neurons. To evaluate the role of this downregulation, we examined
      the relationship between Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      activation and Cdk5 downregulation, as events downstream from NMDA stimulation.
      Glutamate or NMDA stimulation induced CaMKII autophosphorylation over a time
      course that mirrored the time course of p35 degradation. To simulate the
      downregulation of postsynaptic Cdk5 in invitro experiments, we used the Cdk5
      inhibitor roscovitine. The inhibition of Cdk5 activity by roscovitine enhanced
      CaMKII autophosphorylation and activation in cultured neurons, and in an isolated
      postsynaptic-density-enriched fraction. These results suggest that Cdk5 activity
      suppresses CaMKII activation, and that the downregulation of Cdk5 activity after
      treatment withNMDA facilitates CaMKII activation, leading to the easier induction
      of long-term potentiation.

PMID- 16802323
TI  - Rural/nonrural differences in colorectal cancer incidence in the United States,
      1998-2001.
AB  - BACKGROUND: Few studies of colorectal cancer incidence by rural, suburban, and
      metropolitan residence have been published. METHODS: The authors examined
      colorectal cancer incidence among men and women in U.S. counties classified as
      rural, suburban, and metropolitan for the period 1998-2001. They examined
      rural/suburban/metropolitan differences in incidence by age, race, Hispanic
      ethnicity, stage at diagnosis, histology, and percentage of the total county
      population below the poverty level, using data from the CDC's National Program of
      Cancer Registries, the NCI's Surveillance, Epidemiology, and End Results Program,
      and the 2000 U.S. Census. RESULTS: A total of 495,770 newly diagnosed or incident
      cases of colorectal cancer were included in this analysis (249,919 among men and
      245,851 among women). Over the period 1998-2001, the colorectal cancer incidence
      rates among men tended to be lower among those who resided in rural areas, for
      each of the subgroups examined, with the exception of Asians and Pacific
      Islanders and those living in more affluent counties. Among women aged 75 years
      and older, the colorectal cancer incidence rates tended to be lower among rural
      than metropolitan or suburban residents, though the differences were slight. In
      multivariate analysis, the incidence of colorectal cancer was higher in
      metropolitan, suburban, and rural areas for blacks than that for whites
      (incidence rate ratios [RR] = 1.12, 1.07, and 1.06, respectively, all P < 0.015).
      CONCLUSIONS: This study suggests that black men who reside in metropolitan areas
      have a higher risk of colorectal cancer than black men who reside in rural areas.
      This finding suggests the need for diverse approaches for reducing colorectal
      cancer when targeting rural compared with metropolitan areas.

PMID- 16802324
TI  - Associations of subsite-specific colorectal cancer incidence rates and stage of
      disease at diagnosis with county-level poverty, by race and sex.
AB  - BACKGROUND: This study examined associations of subsite-specific colorectal
      cancer incidence rates and stage of the disease with county-level poverty.
      METHODS: The 1998-2001 colorectal cancer incidence data, covering 75% of the
      United States population, were from 38 states and metropolitan areas. The county
      level poverty data were categorized into 3 groups according to the percentage of
      the population below the poverty level in 1999: <10% (low-poverty), 10%-19%
      (middle-poverty), and >or=20% (high-poverty). Age-adjusted subsite-specific
      incidence rates (for all ages) and stage-specific incidence rates (for ages
      >or=50) were examined by race (whites and blacks), sex, and the county's poverty
      level. The differences in the incidence rates were examined using the 2-tailed z
      statistic. RESULTS: The incidence rates of proximal colon cancer were higher
      among white males (11% higher) and white females (15% higher) in the low-poverty
      than in the high-poverty counties. No differences across county poverty levels
      were observed among whites for distal colon and rectal cancers or among blacks
      for all the subsites. The late-to-early stage incidence rate ratios were higher
      in the high-poverty than in the low-poverty counties among white and black males
      for distal colon and rectal cancers, among white females for distal colon cancer,
      and among black females for rectal cancer. For proximal colon cancer, however,
      the late-to-early stage rate ratios were similar across all county poverty
      levels. CONCLUSIONS: Higher incidence rates of proximal cancer were observed
      among white males and females in the low-poverty counties relative to the high
      poverty counties. The higher late-to-early stage rate ratios in high-poverty than
      in low-poverty counties is observed for distal colon and rectal cancers, but not
      for proximal colon cancer.

PMID- 16802325
TI  - A population-based study of colorectal cancer histology in the United States,
      1998-2001.
AB  - BACKGROUND: Histology is an important factor in the etiology, treatment, and
      prognosis of cancer. The purpose of this study was to descriptively characterize
      colorectal cancer (CRC) histology in the United States population. METHODS: Data
      from cancer registries in the National Program of Cancer Registries (NPCR) or
      Surveillance, Epidemiology and End Results (SEER) program, representing 88% of
      the U.S. population, were used in the study. The analysis included 522,630
      microscopically confirmed CRC cases diagnosed from 1998-2001. RESULTS: About 96%
      of CRCs were adenocarcinomas, approximately 2% were other specified carcinomas
      (including carcinoid tumors), about 0.4% were epidermoid carcinomas, and about
      0.08% were sarcomas. The proportion of epidermoid carcinomas, mucin-producing
      carcinomas, and carcinoid tumors was greater among females. Several histologic
      patterns with regard to race and ethnicity existed, including a higher percentage
      of carcinoid tumors among most non-white populations. With respect to age, higher
      percentages of sarcomas, mucin-producing adenocarcinomas, signet ring cell
      tumors, and carcinoid tumors were found in individuals under age 40. Overall,
      adenocarcinomas were more likely to be diagnosed at regional stages with moderate
      differentiation. Compared with other adenocarcinomas, signet ring cell tumors
      were more often poorly differentiated and were at distant stage at diagnosis.
      Carcinoid tumors and sarcomas were mainly poorly differentiated and were at
      localized stage at diagnosis. Small cell carcinomas were more likely
      undifferentiated and were at distant stage at diagnosis. CONCLUSIONS: To date,
      this is the largest population-based study to analyze CRC histology in the United
      States. Distinct demographic and clinical patterns associated with different
      histologies may be helpful for future epidemiologic, laboratory, and clinical
      studies.

PMID- 16802326
TI  - CDC-funded intervention research aimed at promoting colorectal cancer screening
      in communities.
AB  - BACKGROUND: Although strong scientific evidence has shown that screening for
      colorectal cancer saves lives, most U.S. adults who are at the recommended age
      are not being screened. Prior studies suggest that barriers to routine screening
      vary by race, ethnicity, socioeconomic status, urban/rural residence, health
      insurance status, and factors related to health care providers and the health
      care environment. Relatively few studies, however, have identified and tested
      intervention approaches to promote routine colorectal cancer screening among
      diverse populations. METHODS: The Division of Cancer Prevention and Control at
      CDC has funded ongoing projects to develop and test interventions to promote
      routine colorectal cancer screening among medically underserved populations in
      Appalachia, the Lower Rio Grande Valley in Texas, the High Plains region of
      Colorado, and other U.S. communities. RESULTS: This article provides an overview
      of colorectal cancer screening intervention studies currently funded by CDC that
      focus on a wide range of populations, including medically underserved persons who
      live in predominately rural areas, Hispanic and non-Hispanic persons, urban
      African Americans, persons with low health literacy, and persons enrolled in
      managed care organizations. CONCLUSIONS: These CDC-funded intervention research
      projects are likely to contribute importantly to evidence about what works to
      promote colorectal cancer screening in diverse U.S. communities. .

PMID- 16802327
TI  - Pre- and postnatal findings in trisomy 17 mosaicism.
AB  - Trisomy 17 mosaicism is one of the rarest autosomal trisomies in humans. Thus
      far, only 23 cases have been described, most of them detected prenatally. In only
      five instances has mosaicism been demonstrated in lymphocytes and/or fibroblasts
      postnatally, and only in these have multiple congenital anomalies (MCA), facial
      dysmorphisms, and mental retardation been reported. Patients with trisomy 17
      mosaicism at amniocentesis and a normal karyotype in blood and fibroblasts (n =
      17) were always healthy. Here, we report on pre- and postnatal clinical,
      cytogenetic, molecular-cytogenetic, and molecular findings in four patients with
      trisomy 17 mosaicism. The first case was detected in cultured but not in short
      term chorionic villi and amniocytes. Due to MCA on prenatal ultrasound
      examination the pregnancy was terminated. The second patient is a 13-month-old
      healthy boy, in whom low level trisomy 17 mosaicism was detected in cultured
      chorionic villi only. The third patient is a 2-year-old girl with growth
      retardation, developmental delay, MCA, and trisomy 17 mosaicism in amniocytes,
      fibroblasts, and placenta, but not in blood and buccal smear. The fourth patient
      is a 9-year-old boy with growth and mental retardation, sensoneurinal hearing
      loss, and MCA. Cytogenetic analyses showed trisomy 17 mosaicism in amniocytes,
      skin fibroblasts, and urinary sediment cells, whereas in blood and buccal smear a
      46,XY karyotype was found. Molecular investigations in all four cases indicated
      biparental inheritance of chromosome 17. Formation of trisomy was most likely due
      to a maternal meiosis I error in Patient 1 and a postzygotic non-disjunction of
      the paternal chromosome 17 in Patient 4. Cerebellar malformations, reported in
      two cases from the literature and in two reported here may be a specific feature
      of trisomy 17 mosaicism. Since the aberration has rarely been reported in
      lymphocytes, chordocentesis is not indicated in prenatal diagnosis. Prenatal
      genetic counseling for trisomy 17 mosaicism in chorionic villi or amniocytes
      should consider that the clinical significance remains uncertain.

PMID- 16802328
TI  - Quantification of astaxanthin in shrimp waste hydrolysate by HPLC.
AB  - In the present study, a simple and rapid reversed-phase HPLC method for the
      determination of astaxanthin in shrimp waste hydrolysate has been developed and
      validated. The analytical procedure involves the direct extraction of astaxanthin
      from the lipid fraction with methanol. The analytical column, SS Exil ODS, was
      operated at 25C. The mobile phase consisted of a mixture of
      water:methanol:dichloromethane:acetonitrile (4.5:28:22:45.5 v/v/v/v) at a flow
      rate of 1.0 mL/min. Detection and identification were performed using a
      photodiode array detector (lambda(detection) = 476 nm). The proposed HPLC method
      showed adequate linearity, repeatability and accuracy.

PMID- 16802330
TI  - EphA4 regulates central nervous system vascular formation.
AB  - Molecules involved in axon guidance have recently also been shown to play a role
      in blood vessel guidance. To examine whether axon guidance molecules, such as the
      EphA4 receptor tyrosine kinase, might also play a role in development of the
      central nervous system (CNS) vasculature and repair following CNS injury, we
      examined wild-type and EphA4 null mutant (-/-) mice. EphA4-/- mice exhibited an
      abnormal CNS vascular structure in both the cerebral cortex and the spinal cord,
      with disorganized branching and a 30% smaller diameter. During development, EphA4
      was expressed on endothelial cells. This pattern of expression was not maintained
      in the adult. After spinal cord injury in wild-type mice, expression of EphA4 was
      markedly up-regulated on activated astrocytes, many of which were tightly
      associated with blood vessels. In EphA4-/- spinal cord following injury,
      astrocytes were not as tightly associated with blood vessels as the wild-type
      astrocytes. In uninjured EphA4-/- mice, the blood-brain barrier (BBB) appeared
      normal, but it showed prolonged leakage following spinal cord injury. These
      results support a role for EphA4 in CNS vascular formation and guidance during
      development and an additional role in BBB repair.

PMID- 16802329
TI  - Distribution, morphology, and synaptic targets of corticothalamic terminals in
      the cat lateral posterior-pulvinar complex that originate from the posteromedial
      lateral suprasylvian cortex.
AB  - The lateral posterior (LP) nucleus is a higher order thalamic nucleus that is
      believed to play a key role in the transmission of visual information between
      cortical areas. Two types of cortical terminals have been identified in higher
      order nuclei, large (type II) and smaller (type I), which have been proposed to
      drive and modulate, respectively, the response properties of thalamic cells
      (Sherman and Guillery [1998] Proc. Natl. Acad. Sci. U. S. A. 95:7121-7126). The
      aim of this study was to assess and compare the relative contribution of driver
      and modulator inputs to the LP nucleus that originate from the posteromedial part
      of the lateral suprasylvian cortex (PMLS) and area 17. To achieve this goal, the
      anterograde tracers biotinylated dextran amine (BDA) or Phaseolus vulgaris
      leucoagglutinin (PHAL) were injected into area 17 or PMLS. Results indicate that
      area 17 injections preferentially labelled large terminals, whereas PMLS
      injections preferentially labelled small terminals. A detailed analysis of PMLS
      terminal morphology revealed at least four categories of terminals: small type I
      terminals (57%), medium-sized to large singletons (30%), large terminals in
      arrangements of intermediate complexity (8%), and large terminals that form
      arrangements resembling rosettes (5%). Ultrastructural analysis and postembedding
      immunocytochemical staining for gamma-aminobutyric acid (GABA) distinguished two
      types of labelled PMLS terminals: small profiles with round vesicles (RS
      profiles) that contacted mostly non-GABAergic dendrites outside of glomeruli and
      large profiles with round vesicles (RL profiles) that contacted non-GABAergic
      dendrites (55%) and GABAergic dendritic terminals (45%) in glomeruli. RL profiles
      likely include singleton, intermediate, and rosette terminals, although future
      studies are needed to establish definitively the relationship between light
      microscopic morphology and ultrastructural features. All terminals types appeared
      to be involved in reciprocal corticothalamocortical connections as a result of an
      intermingling of terminals labelled by anterograde transport and cells labelled
      by retrograde transport. In conclusion, our results indicate that the origin of
      the driver inputs reaching the LP nucleus is not restricted to the primary visual
      cortex and that extrastriate visual areas might also contribute to the basic
      organization of visual receptive fields of neurons in this higher order nucleus.

PMID- 16802331
TI  - Synaptogenesis in the mushroom body calyx during metamorphosis in the honeybee
      Apis mellifera: an electron microscopic study.
AB  - The goals of this study are to determine relationships between synaptogenesis and
      morphogenesis within the mushroom body calyx of the honeybee Apis mellifera and
      to find out how the microglomerular structure characteristic for the mature calyx
      is established during metamorphosis. We show that synaptogenesis in the mushroom
      body calycal neuropile starts in early metamorphosis (stages P1-P3), before the
      microglomerular structure of the neuropile is established. The initial step of
      synaptogenesis is characterized by the rare occurrence of distinct synaptic
      contacts. A massive synaptogenesis starts at stage P5, which coincides with the
      formation of microglomeruli, structural units of the calyx that are composed of
      centrally located presynaptic boutons surrounded by spiny postsynaptic endings.
      Microglomeruli are assembled either via accumulation of fine postsynaptic
      processes around preexisting presynaptic boutons or via ingrowth of thin neurites
      of presynaptic neurons into premicroglomeruli, tightly packed groups of spiny
      endings. During late pupal stages (P8-P9), addition of new synapses and
      microglomeruli is likely to continue. Most of the synaptic appositions formed
      there are made by boutons (putative extrinsic mushroom body neurons) into small
      postsynaptic profiles that do not exhibit presynaptic specializations (putative
      intrinsic mushroom body neurons). Synapses between presynaptic boutons
      characteristic of the adult calyx first appear at stage P8 but remain rare toward
      the end of metamorphosis. Our observations are consistent with the hypothesis
      that most of the synapses established during metamorphosis provide the structural
      basis for afferent information flow to calyces, whereas maturation of local
      synaptic circuitry is likely to occur after adult emergence.

PMID- 16802332
TI  - Localization of nerve growth factor, neurotrophin-3, and glial cell line-derived
      neurotrophic factor in nestin-expressing reactive astrocytes in the caudate
      putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/Bl mice.
AB  - To address the hypothesis that reactive astrocytes in the basal ganglia of an
      animal model of Parkinson's disease serve neurotrophic roles, we studied the
      expression pattern of neurotrophic factors in the basal ganglia of C57/Bl mice
      that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to
      induce the degeneration of nigral dopamine neurons and parkinsonism. MPTP induced
      significant neuronal degeneration in the substantia nigra pars compacta as
      detected with Fluoro-Jade B staining, and this was accompanied by an increase in
      nestin-expressing astrocytes within the caudate-putamen. The number of nestin
      positive reactive astrocytes in the caudate-putamen peaked within 3-5 days
      following MPTP treatment and then declined progressively toward the basal level
      by 21 days after treatment. Immunofluorescence and confocal microscopy confirmed
      coexpression of nestin or Ki-67 (cell proliferation marker) in glial fibrillary
      acid protein-positive astrocytes in the caudate-putamen. Double immunolabeling
      further revealed immunoreactivities for nerve growth factor (NGF), neurotrophin-3
      (NT3), and glial cell line-derived neurotrophic factor (GDNF) in nestin-positive
      reactive astrocytes. Semiquantification of data obtained from mice 5 days after
      MPTP injection indicated that the majority of nestin-expressing cells expressed
      NGF (92%), NT3 (90%), or GDNF (86%). Our results present novel evidence of
      neurotrophic features among reactive astrocytes in the dopamine-depleted
      striatum. These nestin-expressing reactive astrocytes may therefore play
      neurotrophic roles in neural remodeling of the basal ganglia in Parkinson's
      disease.

PMID- 16802333
TI  - Characterization of neurons in the rat central nucleus of the amygdala: cellular
      physiology, morphology, and opioid sensitivity.
AB  - The central nucleus of the amygdala (CeA) orchestrates autonomic and other
      behavioral and physiological responses to conditioned stimuli that are aversive
      or elicit fear. As a related CeA function is the expression of hypoalgesia
      induced by conditioned stimuli or systemic morphine administration, we examined
      postsynaptic opioid modulation of neurons in each major CeA subdivision.
      Following electrophysiological recording, biocytin-filled neurons were precisely
      located in CeA regions identified by chemoarchitecture (enkephalin
      immunoreactivity) and cytoarchitecture (DAPI nuclear staining) in fixed adult rat
      brain slices. This revealed a striking distribution of physiological types, as
      92% of neurons in capsular CeA were classified as late-firing, whereas no neurons
      in the medial CeA were of this class. In contrast, 60% or more of neurons in the
      lateral and medial CeA were low-threshold bursting neurons. Mu-opioid receptor
      (MOPR) agonists induced postsynaptic inhibitory potassium currents in 61% of CeA
      cells, and this ratio was maintained in each subdivision and for each
      physiological class of neuron. However, MOPR agonists more frequently inhibited
      bipolar/fusiform cells than triangular or multipolar neurons. A subpopulation of
      MOPR-expressing neurons were also inhibited by delta opioid receptor agonists,
      whereas a separate population were inhibited kappa opioid receptors (KOPR). The
      MOPR agonist DAMGO inhibited 9/9 CeM neurons with projections to the parabrachial
      nucleus identified by retrograde tracer injection. These data support models of
      striatopallidal organization that have identified striatal-like and pallidal-like
      CeA regions. Opioids can directly inhibit output from each subdivision by
      activating postsynaptic MOPRs or KOPRs on distinct subpopulations of opioid
      sensitive neurons.

PMID- 16802334
TI  - Systematic analysis of the visual projection neurons of Drosophila melanogaster.
      I. Lobula-specific pathways.
AB  - In insects, visual information is processed in the optic lobe and conveyed to the
      central brain. Although neural circuits within the optic lobe have been studied
      extensively, relatively little is known about the connection between the optic
      lobe and the central brain. To understand how visual information is read by the
      neurons of the central brain, and what kind of centrifugal neurons send the
      control signal from the central brain to the optic lobe, we performed a
      systematic analysis of the visual projection neurons that connect the optic lobe
      and the central brain of Drosophila melanogaster. By screening approximately
      4,000 GAL4 enhancer-trap strains we identified 44 pathways. The overall
      morphology and the direction of information of each pathway were investigated by
      expressing cytoplasmic and presynapsis-targeted fluorescent reporters. A
      canonical nomenclature system was introduced to describe the area of projection
      in the central brain. As the first part of a series of articles, we here describe
      14 visual projection neurons arising specifically from the lobula. Eight pathways
      form columnar arborization in the lobula, whereas the remaining six form
      tangential or tree-like arborization. Eleven are centripetal pathways, among
      which nine terminate in the ventrolateral protocerebrum. Terminals of each
      columnar pathway form glomerulus-like structures in different areas of the
      ventrolateral protocerebrum. The posterior lateral protocerebrum and the optic
      tubercle were each contributed by a single centripetal pathway. Another pathway
      connects the lobula on each side of the brain. Two centrifugal pathways convey
      signals from the posterior lateral protocerebrum to the lobula.

PMID- 16802335
TI  - Focal projections of cat auditory cortex to the pontine nuclei.
AB  - The pontine nuclei (PN) receive projections from the auditory cortex (AC) and
      they are a major source of mossy fibers to the cerebellum. However, they have not
      been studied in detail using sensitive neuroanatomical tracers, and whether all
      AC areas contribute to the corticopontine (CP) system is unknown. We
      characterized the projection patterns of 11 AC areas with WGA-HRP. We also
      compared them with their corticothalamic and corticocollicular counterparts. A
      third objective was to analyze the structure of the CP axons and their terminals
      with BDA. Both tracers confirm that all AC areas projected to lateral, central,
      and medial ipsilateral pontine divisions. The strongest CP projections were from
      nontonotopic and polymodal association areas. Preterminal fibers formed single
      terminal fields having many boutons en passant as well as terminal endings, and
      there was a specific morphological pattern for each pontine target, irrespective
      of their areal origin. Thus, axons in the medial division had a simpler terminal
      architecture (type 1 terminal plexus); both the central and lateral pons received
      more complex endings (type 2 terminal plexus). Auditory CP topographical
      distribution resembled visual and somatosensory CP projections, which preserve
      retinotopy and somatotopy in the pons, respectively. However, the absence of
      pontine tonotopy suggests that the AC projection topography is unrelated to
      tonotopy. CP input to the medial and central pons coincides with the
      somatosensory and visual cortical inputs, respectively, and such overlap might
      subserve convergence in the cerebellum. In contrast, lateral pontine input may be
      exclusively auditory.

PMID- 16802336
TI  - Embryonic origin of the Drosophila brain neuropile.
AB  - Neurons of the Drosophila larval brain are formed by a stereotyped set of
      neuroblasts. As differentiation sets in, neuroblast lineages produce axon bundles
      that initially form a scaffold of unbranched fibers in the center of the brain
      primordium. Subsequently, axons elaborate interlaced axonal and dendritic arbors,
      which, together with sheath-like processes formed by glial cells, establish the
      neuropile compartments of the larval brain. By using markers that visualize
      differentiating axons and glial cells, we have analyzed the formation of
      neuropile compartments and their relationship to neuroblast lineages. Neurons of
      each lineage extend their axons as a cohesive tract ("primary axon bundle"). We
      generated a map of the primary axon bundles that visualizes the location of the
      primary lineages in the brain cortex where the axon bundles originate, the
      trajectory of the axon bundles into the neuropile, and the relationship of these
      bundles to the early-formed scaffold of neuropile pioneer tracts (Nassif et al.
      [1998] J. Comp. Neurol. 402:10-31). The map further shows the growth of neuropile
      compartments at specific locations around the pioneer tracts. Following the time
      course of glial development reveals that glial processes, which form prominent
      septa around compartments in the larval brain, appear very late in the embryonic
      neuropile, clearly after the compartments themselves have crystallized. This
      suggests that spatial information residing within neurons, rather than glial
      cells, specifies the location and initial shape of neuropile compartments.

PMID- 16802337
TI  - Patterning of coronary arteries in wildtype and connexin43 knockout mice.
AB  - Abnormal patterning of coronary arteries (CAs) is a clinically significant
      problem, and as yet, few animal models have been systematically investigated for
      coronary patterning defects. Here we characterized coronary artery (CA) insertion
      and branching patterns of the proximal coronary stems in the hearts of wildtype
      and heterozygous connexin43 knockout (Cx43alpha1 KO) mice. This study entailed
      the use of high-resolution micro CT imaging for three-dimensional coronary
      reconstructions. MicroCT of 17 wildtype mice showed a remarkably consistent
      pattern of CA deployment in the normal mouse heart. Two main CA stems are
      inserted from the left and right into the aorta. The right coronary artery then
      branches immediately into the right main and the septal-conal branch, while the
      left coronary artery branches further distally into the circumflex and the
      anterior descending CA. This patterning of CA anatomy was confirmed by histology,
      and by using a vascular smooth muscle or endothelial cell specific lacZ reporter
      gene to delineate the CAs. A parallel analysis of 25 heterozygous Cx43alpha1 KO
      mouse hearts showed 22 had defects in patterning of the CAs. They exhibited a
      wide variation in CA anatomy, including abnormal origin and course of the main CA
      stems, multiple accessories, and dual septal-conal branches. Overall, these
      studies show loss of one Cx43alpha1 allele (haploinsufficiency) leads to a high
      incidence of coronary patterning defects. These findings suggest CA patterning is
      sensitive to Cx43alpha1 gene dosage.

PMID- 16802338
TI  - Formation of three-dimensional fetal myocardial tissue cultures from rat for long
      term cultivation.
AB  - Three-dimensional cardiomyocyte cultures offer new possibilities for the analysis
      of cardiac cell differentiation, spatial cellular arrangement, and time-specific
      gene expression in a tissue-like environment. We present a new method for
      generating homogenous and robust cardiomyocyte tissue cultures with good long
      term viability. Ventricular heart cells prepared from fetal rats at embryonic day
      13 were cultured in a scaffold-free two-step process. To optimize the cell
      culture model, several digestion protocols and culture conditions were tested.
      After digestion of fetal cardiac ventricles, the resultant cell suspension of
      isolated cardiocytes was shaken to initialize cell aggregate formation. In the
      second step, these three-dimensional cell aggregates were transferred onto a
      microporous membrane to allow further microstructure formation. Autonomously
      beating cultures possessed more than 25 cell layers and a homogenous distribution
      of cardiomyocytes without central necrosis after 8 weeks in vitro. The
      cardiomyocytes showed contractile elements, desmosomes, and gap junctions
      analyzed by immunohistochemistry and electron microscopy. The beat frequency
      could be modulated by adrenergic agonist and antagonist. Adenoviral green
      fluorescent protein transfer into cardiomyocytes was possible and highly
      effective. This three-dimensional tissue model proved to be useful for studying
      cell-cell interactions and cell differentiation processes in a three-dimensional
      cell arrangement.

PMID- 16802339
TI  - Tumor necrosis factor-neutralizing therapies improve altered hormone axes: an
      alternative mode of antiinflammatory action.

PMID- 16802340
TI  - Increased case fatality rates following a first acute cardiovascular event in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: Among patients with rheumatoid arthritis (RA), cardiovascular
      mortality is increased compared with the rate among unaffected peers. In this
      study, 30-day mortality rates following a first acute cardiovascular event
      (myocardial infarction or stroke) were compared between RA patients and the
      general population. METHODS: All cases of a first acute cardiovascular event
      between July 1, 2001 and November 30, 2003 in Victoria, Australia were identified
      from hospital discharge data. Individuals were classified as having RA when an
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) or an International Statistical Classification of Diseases and Related
      Health Problems, Tenth Revision, Australian Modification code for RA was recorded
      at the index admission or during the previous 5 years. Thirty-day mortality rates
      were determined from linkage to the state death registry. RESULTS: A total of
      29,924 patients experienced a first cardiovascular event during the study period,
      359 (1.2%) of whom had RA. Thirty-day cardiovascular mortality was 17.6% in RA
      patients versus 10.8% in non-RA patients. In fully adjusted models, the odds
      ratio (OR) for cardiovascular death in RA patients following a first acute
      cardiovascular event was 1.6 (95% confidence interval [95% CI] 1.2-2.2). Analysis
      of index event subgroups revealed that this increased case fatality rate in
      patients with RA was accounted for almost entirely by excess deaths following
      myocardial infarction. The adjusted ORs for cardiovascular death in RA after
      myocardial infarction and stroke were 1.9 (95% CI 1.3-2.7) and 1.2 (95% CI 0.7
      2.0), respectively. CONCLUSION: RA patients have a substantially increased risk
      of 30-day case fatality following myocardial infarction, but not stroke, compared
      with non-RA patients. This higher case fatality rate is likely to contribute to
      the observed overall excess of cardiovascular deaths in RA populations.

PMID- 16802341
TI  - Effect of valine on the efficiency and precision at S4 cleavage of the Notch-1
      transmembrane domain.
AB  - Presenilin-dependent intramembranous proteolysis mediates the dual cleavage of
      the Notch-1 protein (S4 and S3) as well as the beta amyloid precursor protein
      (betaAPP) (gamma40 and epsilon-site). betaAPP has a valine residue just before
      the gamma40 (amyloid beta [Abeta] numbering) site and after the epsilon-site.
      Both gamma40 and epsilon have multiple cleavage sites, and the varieties of
      gamma40 cleavage are associated with Alzheimer's disease (AD). These lines of
      evidence suggest that valine plays a role in the intramembranous proteolysis. S4
      cleavage in the middle of the Notch-1 transmembrane domain (TMD) corresponds to
      the gamma40 cleavage of betaAPP. The cleavage site is in the center of four
      sequential alanine residues between Ala1731 and Ala1732, neither of which has a
      valine residue. To investigate the effects of valine on presenilin-dependent
      intramembranous proteolysis, we replaced the transmembrane domain residue of
      Notch-1 with valine and analyzed the efficiency and precision at S4 and S3. We
      observed that all valine-mutated Notch-1 proteins have a dominant cleavage site
      (S4) between Ala1731 and Ala1732 with some variations of cleavage precision,
      suggesting that valine is not indispensable for determining the cleavage site of
      the Notch-1 transmembrane domain, but affects the efficiency and precision at S4
      cleavage of the Notch-1 transmembrane domain.

PMID- 16802342
TI  - Direct modulation of rheumatoid inflammatory mediator expression in
      retinoblastoma protein-dependent and -independent pathways by cyclin-dependent
      kinase 4/6.
AB  - OBJECTIVE: It is known that the cyclin-dependent kinase inhibitor (CDKI) gene
      p21(Cip1) suppresses rheumatoid inflammation by down-modulating type I
      interleukin-1 receptor (IL-1RI) expression and inhibiting JNK activity. The
      purpose of this study was to determine whether CDK activity directly modulates
      the production of inflammatory molecules in patients with rheumatoid arthritis
      (RA). METHODS: Genes for the CDKIs p16(INK4a) and p18(INK4c), a constitutively
      active form of retinoblastoma (RB) gene product, cyclin D1, and CDK-4, were
      transferred into RA synovial fibroblasts (RASFs). RASFs were also treated with a
      synthetic CDK-4/6 inhibitor (CDK4I). Levels of matrix metalloproteinase 3 (MMP
      3), monocyte chemoattractant protein 1 (MCP-1), and IL-1RI expression were
      determined by Northern blotting, real-time polymerase chain reaction analysis,
      and enzyme-linked immunosorbent assay. CDKIs were immunoprecipitated to reveal
      their association with JNK. RESULTS: Transfer of the p16(INK4a) and p18(INK4c)
      genes and CDK4I suppressed the production of MMP-3 and MCP-1. Unlike p21(Cip1),
      neither CDKI gene inhibited IL-1RI or JNK. The expression of MMP-3 was up
      regulated when CDK-4 activity was augmented. This regulation functioned at the
      messenger RNA (mRNA) level in MMP-3, but not in MCP-1. Transfer of active RB
      suppressed the production of MMP-3 and MCP-1 without changing their mRNA levels.
      CONCLUSION: CDK-4/6 modulated the production of MMP-3 and MCP-1. MMP-3 production
      was regulated primarily at the mRNA level in an RB-independent manner, whereas
      MCP-1 production was controlled posttranscriptionally by RB. These results show
      that cell cycle proteins are associated with control of mediators of inflammation
      through multiple pathways.

PMID- 16802343
TI  - Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin
      6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether interleukin-6 (IL-6) trans-signaling directs the
      expression of pre-B cell colony-enhancing factor (PBEF) in vitro and in vivo.
      METHODS: Complementary DNA from rheumatoid arthritis (RA) synovial fibroblasts
      treated with IL-6 and soluble IL-6 receptor (sIL-6R) was used to probe a cytokine
      microarray. PBEF regulation by the IL-6-related cytokines, IL-6, sIL-6R,
      oncostatin M (OSM), IL-11, and leukemia inhibitory factor (LIF) was determined by
      reverse transcription-polymerase chain reaction analysis. IL-6-mediated STAT-3
      regulation of PBEF was determined using a cell-permeable STAT-3 inhibitor
      peptide. Antigen-induced arthritis (AIA) was induced in wild-type (IL-6(+/+)) and
      IL-6-deficient (IL-6(-/-)) mice. PBEF and STAT were detected by
      immunohistochemistry, immunoblotting, and electrophoretic mobility shift assay.
      Synovial levels of PBEF were quantified by enzyme immunoassay. RESULTS: IL-6
      trans-signaling regulated PBEF in a STAT-3-dependent manner. In addition, PBEF
      was regulated by the IL-6-related cytokine OSM, but not IL-11 or LIF. Flow
      cytometric analysis of the IL-6-related cognate receptors suggested that OSM
      regulates PBEF via its OSM receptor beta and not its LIF receptor. The
      involvement of PBEF in arthritis progression was confirmed in vivo, where
      induction of AIA resulted in a 4-fold increase in the synovial expression of
      PBEF. In contrast, little or no change was observed in IL-6(-/-) mice, in which
      the inflammatory infiltrate was markedly reduced and synovial STAT-1/3 activity
      was also impaired. Analysis of human RA synovial tissue confirmed that PBEF
      immunolocalized in apical synovial membrane cells, endothelial cells, adipocytes,
      and lymphoid aggregates. Synovial fluid levels of PBEF were significantly higher
      in RA patients than in osteoarthritis patients. CONCLUSION: Experiments presented
      herein demonstrate that PBEF is regulated via IL-6 trans-signaling and the IL-6
      related cytokine OSM. PBEF is also actively expressed during arthritis. Although
      these data confirm an involvement of PBEF in disease progression, the consequence
      of its action remains to be determined.

PMID- 16802344
TI  - Differential survival of leukocyte subsets mediated by synovial, bone marrow, and
      skin fibroblasts: site-specific versus activation-dependent survival of T cells
      and neutrophils.
AB  - OBJECTIVE: Synovial fibroblasts share a number of phenotype markers with
      fibroblasts derived from bone marrow. In this study we investigated the role of
      matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and
      skin) to test the hypothesis that synovial fibroblasts share similarities with
      bone marrow-derived fibroblasts in terms of their ability to support survival of
      T cells and neutrophils. METHODS: Matched synovial, bone marrow, and skin
      fibroblasts were established from 8 different patients with rheumatoid arthritis
      who were undergoing knee or hip surgery. Resting or activated fibroblasts were
      cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte
      survival, apoptosis, and proliferation were measured. RESULTS: Fibroblasts
      derived from all 3 sites supported increased survival of CD4 T cells, mediated
      principally by interferon-beta. However, synovial and bone marrow fibroblasts
      shared an enhanced site-specific ability to maintain CD4 T cell survival in the
      absence of proliferation, an effect that was independent of fibroblast activation
      or proliferation but required direct T cell-fibroblast cell contact. In contrast,
      fibroblast-mediated neutrophil survival was less efficient, being independent of
      the site of origin of the fibroblast but dependent on prior fibroblast
      activation, and mediated solely by soluble factors, principally granulocyte
      macrophage colony-stimulating factor. CONCLUSION: These results suggest an
      important functional role for fibroblasts in the differential accumulation of
      leukocyte subsets in a variety of tissue microenvironments. The findings also
      provide a potential explanation for site-specific differences in the pattern of T
      cell and neutrophil accumulation observed in chronic inflammatory diseases.

PMID- 16802345
TI  - Inflammatory cytokine regulation of transgene expression in human fibroblast-like
      synoviocytes infected with adeno-associated virus.
AB  - OBJECTIVE: An ideal gene transfer vector for chronic inflammatory diseases such
      as rheumatoid arthritis (RA) would provide local transgene expression only when
      the disease is active. To determine whether adeno-associated virus (AAV)
      possesses this ability, the effects of inflammatory cytokines on transgene
      expression were evaluated in human RA fibroblast-like synoviocytes (FLS).
      METHODS: Human FLS were infected with AAV in the presence or absence of
      inflammatory cytokines or synovial fluid obtained from patients with RA.
      Transgene expression was monitored by either enzyme-linked immunosorbent assay or
      flow cytometry. Transgene messenger RNA (mRNA) was measured by real-time
      quantitative reverse transcription-polymerase chain reaction. RESULTS:
      Inflammatory cytokines increased transgene expression in FLS by up to 60-fold.
      Synovial fluid from patients with RA, but not from patients without arthritis,
      was also able to increase expression in synoviocytes. Protein expression
      correlated with transgene mRNA levels. The enhanced expression required the
      continued presence of cytokines because, upon removal, transgene expression
      returned to baseline levels. Expression could be repeatedly reinduced by
      reexposure to cytokines. The effect was not promoter specific and was
      demonstrated to be phosphatidylinositol 3-kinase-dependent. CONCLUSION: These
      results suggest that expression of a therapeutic transgene can be controlled by
      the presence of inflammation following AAV gene transfer, making it an attractive
      vector for chronic inflammatory diseases such as RA.

PMID- 16802346
TI  - Overexpression of synoviolin in peripheral blood and synoviocytes from rheumatoid
      arthritis patients and continued elevation in nonresponders to infliximab
      treatment.
AB  - OBJECTIVE: Synoviolin is a novel E3 ubiquitin ligase that has been implicated in
      the pathogenesis of rheumatoid arthritis (RA). The purpose of this study was to
      examine the expression and regulation of synoviolin by tumor necrosis factor
      alpha (TNFalpha), both in vivo and in vitro. METHODS: A total of 54 RA patients
      and 23 healthy control subjects were analyzed before, 4 hours after the first
      infusion, and at week 22 of infliximab treatment. Clinical response was assessed
      by the American College of Rheumatology criteria for 20% improvement and the
      Disease Activity Score in 28 joints (DAS28) at 6 months. Synoviolin messenger RNA
      expression was measured by real-time reverse transcription-polymerase chain
      reaction in peripheral blood (PB) and fibroblast-like synoviocytes (FLS) and with
      and without TNFalpha or interleukin-1beta (IL-1beta) stimulation. RESULTS:
      Synoviolin expression was increased in whole PB obtained from RA patients as
      compared with that from healthy controls and was significantly reduced early and
      late after infliximab treatment in responders, but in not nonresponders.
      Reduction in synoviolin expression was associated with reduced levels of markers
      of disease activity, including C-reactive protein levels. Nonresponders to
      infliximab therapy had significantly higher synoviolin expression at baseline as
      compared with responders, and this elevation persisted despite infliximab
      therapy. PB CD14+ monocytes expressed increased synoviolin levels compared with
      CD3+ lymphocytes, and TNFalpha or IL-1beta induced a further increase in
      expression in CD3+ cells. TNFalpha or IL-1beta induced sustained synoviolin
      expression in RA FLS. CONCLUSION: Elevated PB levels of synoviolin were
      identified in circulating PB mononuclear cells and were associated with
      nonresponse to infliximab treatment. Sustained up-regulation of synoviolin by IL
      lbeta and TNFalpha may contribute to prolonged survival of immune cells and
      dysregulated FLS proliferation, leading to RA chronicity.

PMID- 16802347
TI  - Differentiation of a human neuroblastoma into neuron-like cells increases their
      susceptibility to transduction by herpesviral vectors.
AB  - Gene transfer is a powerful tool for functional gene analysis in human cells. In
      this respect, there is a need to develop experimental models that involve
      homogeneous cultures of human neuron-like cells susceptible to gene transduction
      and that are easy to handle. Here we describe an optimized and reproducible
      procedure to differentiate human SH-SY5Y neuroblastoma cells into a homogeneous
      population of neuron-like cells. The fully differentiated cells are postmitotic
      and resemble primary cultured neurons in terms of their cytoskeletal polarity.
      Notably, differentiated SH-SY5Y cells are far more susceptible to transduction by
      herpes simplex virus (HSV-1)-based vectors than proliferating SH-SY5Y cells. This
      increase in transduction efficiency after neuronal differentiation may be due to
      the up-regulation of cell surface receptors for herpesvirus entry. In summary, we
      propose that fully differentiated human neuron-like cells obtained from the SH
      SY5Y neuroblastoma may constitute an excellent and versatile experimental tool
      for gene transfer and functional genomic studies with HSV-1 vectors.

PMID- 16802348
TI  - Apomorphine protects against 6-hydroxydopamine-induced neuronal cell death
      through activation of the Nrf2-ARE pathway.
AB  - NF-E2-related factor-2 (Nrf2), a basic leucine zipper transcription factor, is
      involved in the expression of numerous detoxifying and antioxidant genes via the
      antioxidant response element (ARE). Apomorphine (Apo), a dopamine D(1)/D(2)
      receptor agonist, is used for clinical therapy of Parkinson's disease. On the
      other hand, Apo is a potent radical scavenger and has protective effects on
      oxidative stress-induced cell death. Previously, we have reported that
      pretreatment of human neuroblastoma SH-SY5Y cells with Apo enhances protection
      against 6-hydroxydopamine (6-OHDA)-induced cell death. In this study, we
      investigated whether the Nrf2-ARE system is involved in the protection by Apo.
      Pretreatment of SH-SY5Y cells with Apo suppressed 6-OHDA-induced cell death in a
      dose-dependent manner. However, neither SCH23390, a dopamine D(1) receptor
      antagonist, nor sulpiride, a dopamine D(2) receptor antagonist, prevented the
      protective effect of Apo. Apo stimulated the translocation of Nrf2 into the
      nucleus and the transactivation of the ARE. The expression of heme oxygenase-1
      (HO-1) was dose dependently induced by Apo. Moreover, we found that the
      activation of the ARE and the induction of HO-1 mRNA caused by Apo were
      suppressed in the presence of the antioxidant N-acetylcysteine and also that Apo
      produced intracellular reactive oxygen species (ROS), indicating that the low
      level of ROS produced by Apo may play a critical role in this phenomenon. Taken
      together, our findings suggest that not only the function as a radical scavenger
      but also the function as an Nrf2-ARE pathway activator may be involved in the
      neuroprotective effects of Apo.

PMID- 16802349
TI  - Regulation of JNK by MKK-7 in fibroblast-like synoviocytes.
AB  - OBJECTIVE: JNK regulates matrix metalloproteinase (MMP) gene expression and joint
      destruction in rheumatoid arthritis (RA). Previous studies demonstrated that the
      2 upstream MAPK kinases (MKK-4 and MKK-7) are phosphorylated in RA synovium and
      form a complex with JNK in fibroblast-like synoviocytes (FLS). However, the
      functional hierarchy of MKK-4 and MKK-7 in FLS has not been determined. We
      determined the relative contributions of these MKKs by evaluating the effect of
      MKK-4 and MKK-7 gene knockdown in cultured FLS. METHODS: FLS were transfected
      with MKK-4 and/or MKK-7 small interfering RNA, and protein levels were determined
      by immunoblotting. After stimulation with interleukin-1/beta (IL-1beta), tumor
      necrosis factor alpha(TNFalpha, or anisomycin, kinase function was determined by
      in vitro kinase assay. Activator protein 1 (AP-1) binding and transcriptional
      activity were determined by electrophoretic mobility shift assay and AP-1
      luciferase promoter assay, respectively. MMP-3 expression was determined by
      enzyme-linked immunosorbent assay and quantitative polymerase chain reaction.
      RESULTS: IL-1beta-induced JNK phosphorylation was dependent on MKK-7 but not on
      MKK-4; however, anisomycin-activated JNK required both kinases. In vitro kinase
      assay demonstrated that IL-1beta-or TNFalpha induced JNK activity was only MKK-7
      dependent, while anisomycin-activated JNK was both MKK-4 and MKK-7 dependent. IL
      1beta-induced AP-1 binding activity and AP-1-driven gene expression were strictly
      MKK-7 dependent. Finally, MMP-3 production only required MKK-7, and there was no
      effect of MKK-4 deficiency. CONCLUSION: These data indicate that only MKK-7 is
      required for JNK activation in FLS after cytokine stimulation; however, other
      forms of cellular stress utilize MKK-4. Thus, JNK function might be modulated by
      targeting MKK-7 to suppress cytokine-mediated FLS activation while leaving other
      stress responses intact.

PMID- 16802350
TI  - Efficacy and safety of adalimumab in patients with ankylosing spondylitis:
      results of a multicenter, randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of adalimumab, a fully human
      recombinant IgG1 monoclonal antibody that specifically targets human tumor
      necrosis factor, in patients with active ankylosing spondylitis (AS). METHODS:
      This was a multicenter, randomized (2:1 ratio), double-blind, placebo-controlled
      study to evaluate a subcutaneous injection of adalimumab, 40 mg every other week,
      compared with placebo for 24 weeks. The primary efficacy end point was the
      percentage of patients with a 20% response according to the ASsessment in
      Ankylosing Spondylitis International Working Group criteria for improvement
      (ASAS20) at week 12. Secondary outcome measures included the ASAS20 at week 24
      and multiple measures of disease activity, spinal mobility, and function, as well
      as ASAS partial remission. RESULTS: At week 12, 58.2% of adalimumab-treated
      patients (121 of 208) achieved an ASAS20 response, compared with 20.6% of placebo
      treated patients (22 of 107) (P < 0.001). More patients in the adalimumab group
      (45.2% [94 of 208]) than in the placebo group (15.9% [17 of 107]) had at least a
      50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index at week
      12 (P < 0.001). Significant improvements in the ASAS40 response and the response
      according to the ASAS5/6 criteria at weeks 12 and 24 were also demonstrated (P <
      0.001). Partial remission was achieved by more adalimumab-treated patients than
      placebo-treated patients (22.1% versus 5.6%; P < 0.001). Adalimumab-treated
      patients reported more adverse events (75.0% versus 59.8% of placebo-treated
      patients; P < 0.05), but there was no statistically significant difference in the
      incidence of infections. Most adverse events were mild or moderate in severity.
      CONCLUSION: Adalimumab was well-tolerated during the 24-week study period and was
      associated with a significant and sustained reduction in the signs and symptoms
      of active AS.

PMID- 16802351
TI  - The heritable determinants of cartilage oligomeric matrix protein.
AB  - OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a cartilage matrix
      macromolecule. The protein is detectable in serum and has been investigated as a
      biomarker of osteoarthritis (OA). An association between COMP and OA has been
      shown, yet the precise factors governing serum levels of COMP remain unclear. The
      aim of this study was to determine whether genetic factors influence serum levels
      of COMP. METHODS: A classic twin study was conducted using COMP levels in serum
      obtained from healthy female twin volunteers. COMP levels were determined by an
      inhibition enzyme-linked immunosorbent assay method. The heritability of COMP was
      determined by comparing correlation among 160 monozygotic and 349 dizygotic twin
      pairs. Data on potential confounding factors, including age, body mass index, and
      the presence of OA as assessed by hand, hip, and knee radiographs, were included
      in the analysis. RESULTS: Serum levels of COMP showed a correlation of 0.72 (95%
      confidence interval [95% CI] 0.65-0.80) among monozygotic twin pairs and 0.47
      (95% CI 0.39-0.55) in dizygotic pairs. This equated to an estimated heritability
      for COMP of 40% (95% CI 20-60%). Although age and body mass index were found to
      be significantly associated with COMP in regression analysis, taking the effects
      of these factors into account did not influence the estimate of heritability.
      CONCLUSION: This study showed that heritable factors influence serum levels of
      the cartilage matrix biomarker COMP. Together with other published data, the
      results suggest that genetic factors operate at an early stage in the etiologic
      pathways that influence the development of radiographically discernible OA.

PMID- 16802352
TI  - Clinical images: B cell depletion in the appendix following rituximab treatment.

PMID- 16802353
TI  - The catabolic pathway mediated by Toll-like receptors in human osteoarthritic
      chondrocytes.
AB  - OBJECTIVE: To examine the catabolic pathways mediated by Toll-like receptor (TLR)
      ligands in human osteoarthritic (OA) chondrocytes. METHODS: The presence of TLRs
      in OA and non-OA articular cartilage was analyzed by immunohistochemistry. The
      regulation of TLR messenger RNA (mRNA) by interleukin-1 (IL-1) and tumor necrosis
      factor alpha (TNFalpha) was analyzed by reverse transcription-polymerase chain
      reaction. For stimulation of TLR-2 and TLR-4, chondrocytes were treated with
      Staphylococcus aureus peptidoglycan and lipopolysaccharides (LPS), respectively.
      Production of matrix metalloproteinases (MMPs) 1, 3, and 13 and prostaglandin E2
      (PGE2) was evaluated by enzyme-linked immunosorbent assay. Production of nitric
      oxide (NO) was analyzed by the Griess reaction. Regulation of cyclooxygenase 2
      protein and phosphorylation of MAPKs (p38, ERK, and JNK) were evaluated by
      Western blotting or solid-phase kinase assay. NF-kappaB activation was evaluated
      by electrophoretic mobility shift assay. RESULTS: Expression of TLRs 2 and 4 was
      up-regulated in lesional areas of OA cartilage. Treatment with IL-1, TNFalpha,
      peptidoglycan, and LPS all significantly up-regulated TLR-2 mRNA expression in
      cultured chondrocytes. Production of MMPs 1, 3, and 13 and of NO and PGE2 was
      significantly increased after treating chondrocytes with either of the TLR
      ligands. Prolonged culture of cartilage explants with TLR ligands also led to a
      significant increase in the release of proteoglycan and type II collagen
      degradation product. Treatment with TLR ligands led to phosphorylation of all 3
      MAPKs and activation of NF-kappaB. CONCLUSION: We found that TLRs are increased
      in OA cartilage lesions. TLR-2 and TLR-4 ligands strongly induce catabolic
      responses in chondrocytes. Modulation of TLR-mediated signaling as a therapeutic
      strategy would require detailed elucidation of the signaling pathways involved.

PMID- 16802354
TI  - Effects of interleukin-1 on calcium signaling and the increase of filamentous
      actin in isolated and in situ articular chondrocytes.
AB  - OBJECTIVE: To determine whether interleukin-1 (IL-1) initiates transient changes
      in the intracellular concentration of [Ca2+]i and the organization of filamentous
      actin (F-actin) in articular chondrocytes. METHODS: Articular chondrocytes within
      cartilage explants and enzymatically isolated chondrocytes were loaded with
      Ca(2+)-sensitive fluorescence indicators, and [Ca2+]i was measured using confocal
      fluorescence ratio imaging during exposure to 10 ng/ml IL-1alpha. Inhibitors of
      Ca2+ mobilization (Ca(2+)-free medium, thapsigargin [inhibitor of Ca-ATPases],
      U73122 [inhibitor of phospholipase C], and pertussis toxin [inhibitor of G
      proteins]) were used to determine the mechanisms of increased [Ca2+]i. Cellular F
      actin was quantified using fluorescently labeled phalloidin. Toxin B was used to
      determine the role of the Rho family of small GTPases in F-actin reorganization.
      RESULTS: In isolated cells on glass and in in situ chondrocytes within explants,
      exposure to IL-1 induced a transient peak in [Ca2+]i that was generally followed
      by a series of decaying oscillations. Thapsigargin, U73122, and pertussis toxin
      inhibited the percentage of cells responding to IL-1. IL-1 increased F-actin
      content in chondrocytes in a manner that was inhibited by toxin B. CONCLUSION:
      Both isolated and in situ chondrocytes respond to IL-1 with transient increases
      in [Ca2+]i via intracellular Ca2+ release mediated by the phospholipase C and
      inositol trisphosphate pathways. The influx of Ca2+ from the extracellular space
      and the activation of G protein-coupled receptors also appear to contribute to
      these mechanisms. These findings suggest that Ca2+ mobilization may be one of the
      first signaling events in the response of chondrocytes to IL-1.

PMID- 16802355
TI  - Anti-20S proteasome autoantibodies inhibit proteasome stimulation by proteasome
      activator PA28.
AB  - OBJECTIVE: The ubiquitin-proteasome system plays a central role in cellular
      homeostasis as well as in regulation of the inflammatory and stress responses.
      However, the occurrence of autoantibodies against 20S proteasome has, to date,
      been considered to be a non-specific epiphenomenon in patients with autoimmune
      disorders. This study was undertaken to analyze the properties of antiproteasome
      antibodies by investigating their influence on the proteolytic activity of the
      proteasome complex. METHODS: The 20S proteasome, with or without addition of the
      proteasome activator (PA28), was preincubated with affinity-purified human
      antiproteasome antibodies. Proteolytic activity was estimated using fluorogenic
      peptides as substrate. RESULTS: The baseline proteolytic properties of the 20S
      proteasome core complex were not influenced by the autoantibodies in vitro. In
      contrast, all human antiproteasome antibodies analyzed efficiently blocked the
      enhanced proteasomal substrate cleavage provided by PA28. A similar influence of
      proteasome activation was observed upon preincubation with affinity-purified
      sheep polyclonal or mouse monoclonal antiproteasome antibody, whereas human
      immunoglobulin controls exhibited no effect. CONCLUSION: Autoantibodies against
      20S proteasomes are able to block proteasome activation by PA28, binding to their
      native antigen in vitro. Antibody targeting of the interaction between 20S
      proteasome and PA28 represents a novel mechanism of proteasome inhibition.

PMID- 16802356
TI  - Abnormal differentiation of memory T cells in systemic lupus erythematosus.
AB  - OBJECTIVE: The chemokine receptor CCR7 and the tumor necrosis factor receptor
      family member CD27 define 3 distinct, progressively more differentiated
      maturational stages of CD4 memory subpopulations in healthy individuals: the
      CCR7+, CD27+, the CCR7-, CD27+, and the CCR7-, CD27- populations. The goal of
      this study was to examine maturational disturbances in CD4 T cell differentiation
      in systemic lupus erythematosus (SLE), using these phenotypic markers. METHODS:
      Phenotypic analysis by flow cytometry, in vitro stimulation experiments, telomere
      length measurement, and determination of inducible telomerase were carried out.
      RESULTS. In SLE patients, significant increases of CCR7-, CD27- and CCR7-, CD27+
      and a reduction of CCR7+, CD27+ CD4 memory T cells were found. In vitro
      stimulation of SLE T cells showed a stepwise differentiation from naive to CCR7+,
      CD27+ to CCR7-, CD27+ to CCR7-, CD27-; telomere length and inducible telomerase
      decreased in these subsets in the same progressive sequence. The in vitro
      proliferative response of these populations progressively declined as their
      susceptibility to apoptosis increased. Interestingly, a significant reduction in
      inducible telomerase was noted in SLE naive and CCR7+, CD27+ CD4+ memory T cells.
      Additionally, SLE CCR7-, CD27+ and CCR7-, CD27- CD4 memory T cells proliferated
      poorly in response to in vitro stimulation and underwent significantly more
      apoptosis than their normal counterparts. Finally, expression of CXCR4 was
      significantly reduced in all SLE subsets compared with normal. CONCLUSION:
      Together these data indicate an increased degree of in vivo T cell stimulation in
      SLE, resulting in the accumulation of terminally differentiated memory T cells
      with a decreased proliferative capacity and an increased tendency to undergo
      apoptosis upon stimulation.

PMID- 16802357
TI  - Association between serum total cholesterol level and renal outcome in systemic
      lupus erythematosus.
AB  - OBJECTIVE: To determine whether an elevated serum total cholesterol level in a
      first-available sample obtained at a systemic lupus erythematosus (SLE) clinic is
      associated with worse renal outcome in patients with SLE. METHODS: Survival
      analysis methods were used on prospectively gathered data on 1,060 patients with
      SLE who were registered in the University of Toronto Lupus Databank. The effect
      of total cholesterol and 15 additional variables on the outcomes of renal
      deterioration, end-stage renal disease (ESRD), and death was assessed using Cox
      proportional hazards methods. RESULTS: In 474 (45%) of the 1,060 patients, the
      total cholesterol level exceeded 5.2 mmoles/liter. In the entire study group, the
      median total cholesterol level was 5.1 mmoles/liter (range 1.6-17.1). During a
      mean followup period of 8.8 years, 93 patients (9%) experienced renal
      deterioration, 42 patients (4%) had ESRD, and 161 deaths occurred, 48 (30%) of
      which were associated with renal dysfunction (renal death), and 113 (70%) of
      which were not associated with renal dysfunction (nonrenal death). Kaplan-Meier
      survival estimates for each outcome were statistically significantly different
      between patients with normal versus those with elevated total cholesterol levels
      (cutoff 5.2 mmoles/ liter), with a worse outcome observed among those with an
      elevated total cholesterol concentration. In multivariate analyses, total
      cholesterol level (hazard ratio [HR] 1.17, 95 confidence interval [95% CI] 1.01
      1.36), serum creatinine level (HR 1.06, 95% CI 1.04-1.07), proteinuria (HR 2.44,
      95% CI 1.25-4.76), the Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index (HR 1.44, 95% CI 1.16
      1.80), and corticosteroid dose (HR 1.01, 95% CI 1.00-1.02) were associated with
      renal deterioration. Significant predictors of ESRD were baseline proteinuria (HR
      6.24, 95% CI 1.96-19.88) and serum creatinine level (HR 1.15, 95% CI 1.08-1.22).
      The total cholesterol level was correlated with death (HR 1.20, 95% CI 1.11
      1.29), retaining statistical significance for renal death (HR 1.33, 95% CI 1.20
      1.47) but not for nonrenal death (HR 1.12, 95% CI 0.99-1.25). CONCLUSION: Those
      results indicate that an elevated serum total cholesterol level in a first
      available sample obtained at an SLE clinic is associated with adverse renal
      outcomes and mortality.

PMID- 16802358
TI  - Homocysteine levels and disease duration independently correlate with coronary
      artery calcification in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To compare the incidence and extent of coronary artery calcification
      (CAC) as measured by electron beam computed tomography (EBCT) in patients with
      systemic lupus erythematosus (SLE) and controls, and to identify variables
      associated with CAC in patients with SLE. METHODS: Female patients with SLE and
      matched controls were recruited; EBCT of the coronary arteries was performed, and
      laboratory values (including the homocysteine concentration, the lipid level, the
      high-sensitivity C-reactive protein [hsCRP] concentration, the glomerular
      filtration rate [GFR], and the level of soluble CD154 [sCD154]) were determined.
      For patients, the Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology Damage Index and the SLE Disease Activity Index scores
      were recorded. Tests of association between the CAC score and the above-mentioned
      variables were performed. RESULTS: The incidence of CAC was higher in patients
      with SLE than in controls (P = 0.009), and patients had a higher mean raw CAC
      (rCAC) score (87.9 versus 9.6 in controls; P = 0.02). In particular, more CAC
      positive patients than CAC-positive controls had rCAC scores above the 75th
      percentile (P = 0.003). Among both patients and controls, those with CAC were
      approximately 10 years older than those without CAC. In addition to age, a
      significant determinant of positive CAC status in both groups was the number of
      cardiovascular risk factors. In patients with SLE, CAC was associated with a
      higher homocysteine concentration, a lower GFR, and longer disease duration. In
      controls, the total cholesterol level correlated positively with CAC. When
      multivariate logistic regression methods were applied to candidate explanatory
      variables, homocysteine concentration, age, and disease duration (but not the
      levels of sCD154 or hsCRP) contributed significantly to CAC status. The
      methylenetetrahydrofolate reductase C677T genotype was not a predictor of
      hyperhomocysteinemia or CAC status. CONCLUSION: Among patients with SLE, the
      homocysteine concentration, the GFR, age, and disease duration were associated
      with CAC. CAC occurred more frequently and was more extensive in patients with
      SLE than in controls, suggesting that EBCT could be used to detect premature
      atherosclerosis in the former group. An elevated homocysteine concentration might
      identify patients with SLE who are likely to have premature atherosclerosis and
      who would benefit from evaluation of CAC by EBCT.

PMID- 16802359
TI  - Anti-La/SSB antiidiotypic antibodies in maternal serum: a marker of low risk for
      neonatal lupus in an offspring.
AB  - OBJECTIVE: The anti-La/SSB response to major B cell epitopes of La/SSB can be
      blocked by an active idiotypic/antiidiotypic network, which can be identified
      using synthetic complementary epitopes deduced from the sequence of the major B
      cell epitopes of the molecule. This study evaluated the role of this network in
      pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies in the development
      of neonatal lupus syndrome (NLS). METHODS: Sixty-three serum samples collected
      from anti-Ro/anti-La-positive women during pregnancy or within 6 months after
      delivery were obtained from the Research Registry for Neonatal Lupus and the PR
      Interval Dexamethasone Evaluation study. These samples, as well as 30 sera from
      healthy individuals, were tested in a blinded manner by enzyme-linked
      immunosorbent assay against synthetic peptides corresponding to major B cell
      epitopes and complementary epitopes of La/SSB. RESULTS: Sera from mothers giving
      birth to a healthy child and having no history of a child with NLS exhibited
      higher antiidiotypic antibody activity compared with mothers carrying a child
      with NLS (P < 0.0001) or mothers giving birth to a healthy child but who
      previously gave birth to a child with NLS (P = 0.0151). Sera from mothers of
      healthy children, which exhibited no apparent epitope activity against amino
      acids 349-364, revealed a significantly greater frequency of hidden anti-349
      364aa epitope responses, blocked by antiidiotypic antibodies, as compared with
      sera from women pregnant with an affected child (P = 0.0094). CONCLUSION: The
      presence of antiidiotypic antibodies to autoantibodies against La/SSB may protect
      the fetus by blocking pathogenic maternal autoantibodies. Testing for these
      antiidiotypic responses may be useful in predicting a decreased risk of NLS.

PMID- 16802360
TI  - A randomized controlled trial of calcium supplementation to increase bone mineral
      density in children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To examine the effects of daily supplementation with calcium (Ca) in
      combination with vitamin D on total body and lumbar spine bone mineral density
      (BMD) in patients with juvenile rheumatoid arthritis (JRA) who had not taken
      corticosteroids for at least 3 months prior to the beginning of the study.
      METHODS: One hundred ninety-eight children and adolescents (141 girls and 57
      boys) with JRA, ages 6 to 18 years, with a mean +/- SD age of 11.7 +/- 3.3 years
      and a mean +/- SD disease duration of 5.6 +/- 3.8 years at the beginning of the
      study, were enrolled in this randomized double-blind, placebo-controlled trial to
      receive either daily oral supplements of 1,000 mg of Ca and 400 IU of vitamin D
      (n = 103) or matched placebo tablets and 400 IU of vitamin D (n = 95) for 24
      months. Total body BMD (TBBMD) was measured by dual x-ray absorptiometry at
      baseline and every 6 months for 24 months. RESULTS: At baseline, the mean +/- SD
      TBBMD was 0.89 +/- 0.14 gm/cm2 among patients randomized to the Ca group and 0.87
      +/- 0.14 gm/cm2 among those randomized to placebo (P = 0.445). At 24 months, the
      mean +/- SD TBBMD among those receiving Ca was 0.95 +/- 0.13 gm/cm2, compared
      with 0.92 +/- 0.14 gm/cm2 among those receiving placebo. A longitudinal random
      effects mixed model analysis that controlled for differences in the subject's
      initial BMD, sex, Tanner stage, adherence to the study medication regimen, and
      body composition revealed significantly higher TBBMD among patients who received
      Ca compared with patients who received placebo during the study period (P =
      0.03). CONCLUSION: Ca supplementation resulted in a small, but statistically
      significant, increase in TBBMD compared with placebo in children with JRA.

PMID- 16802361
TI  - Clinical image: Coexistence of diffuse idiopathic skeletal hyperostosis and
      ossification of the posterior longitudinal ligament of the cervical spine in a
      patient with ankylosing spondylitis.

PMID- 16802362
TI  - Analytical techniques for quantification of amorphous/crystalline phases in
      pharmaceutical solids.
AB  - The existence of different solid-state forms such as polymorphs, solvates,
      hydrates, and amorphous form in pharmaceutical drug substances and excipients,
      along with their downstream consequences in drug products and biological systems,
      is well documented. Out of these solid states, amorphous systems have attracted
      considerable attention of formulation scientists for their specific advantages,
      and their presence, either by accident or design is known to incorporate distinct
      properties in the drug product. Identification of different solid-state forms is
      crucial to anticipate changes in the performance of the material upon storage
      and/or handling. Quantitative analysis of physical state is imperative from the
      viewpoint of both the manufacturing and the regulatory control aimed at assuring
      safety and efficacy of drug products. Numerous analytical techniques have been
      reported for the quantification of amorphous/crystalline phase, and implicit in
      all quantitative options are issues of accuracy, precision, and suitability.
      These quantitative techniques mainly vary in the properties evaluated, thus
      yielding divergent values of crystallinity for a given sample. The present review
      provides a compilation of the theoretical and practical aspects of existing
      techniques, thereby facilitating the selection of an appropriate technique to
      accomplish various objectives of quantification of amorphous systems.

PMID- 16802363
TI  - Systemic sclerosis-associated Sjogren's syndrome and relationship to the limited
      cutaneous subtype: results of a prospective study of sicca syndrome in 133
      consecutive patients.
AB  - OBJECTIVE: To determine the prevalence of sicca symptoms and Sjogren's syndrome
      (SS) in a 2-center prospective series of patients with systemic sclerosis (SSc),
      using the American-European Consensus Group criteria for SS. METHODS: Consecutive
      SSc patients hospitalized for followup care were evaluated for sicca symptoms.
      When the initial clinical evaluation yielded positive findings, a labial salivary
      gland biopsy was performed; histologic analysis evaluated focal lymphocytic
      sialadenitis and/or glandular fibrosis. Computed tomography and respiratory
      function tests were used to assess pulmonary fibrosis. RESULTS: We included 133
      SSc patients (mean +/- SD age 55 +/- 13 years; mean +/- SD disease duration 6.5
      +/- 6 years). Eighty-one patients had limited cutaneous SSc (lcSSc). Ninety-one
      patients (68%) had sicca syndrome. Histologic analysis revealed fibrotic
      involvement in 50 of these 91 patients, but labial salivary gland fibrosis was
      not associated with any organ involvement we evaluated. Nineteen of the 133
      patients (14%) had SS. In this subgroup, lcSSc was present at a significantly
      higher frequency (18 of 19 patients) than in the remaining patients with sicca
      syndrome (39 of 72 patients) and the patients without sicca syndrome (24 of 42
      patients). This subgroup also had a significantly higher frequency of
      anticentromere antibodies (18 of 19 patients) than did the remaining patients
      with sicca syndrome (19 of 72 patients) and the patients without sicca syndrome
      (5 of 42 patients). In addition, this subgroup had a significantly lower
      prevalence of pulmonary fibrosis (2 of 19 patients) than did the remaining
      patients with sicca syndrome (29 of 72 patients) and the patients without sicca
      syndrome (19 of 42 patients). CONCLUSION: There was a 68% prevalence of sicca
      syndrome in this prospective series of SSc patients. Sicca syndrome was related
      primarily to glandular fibrosis, the hallmark of SSc. The prevalence of secondary
      SS, as defined by the American-European Consensus Group criteria, was 14% and was
      markedly associated with lcSSc. We believe that lcSSc should be regarded as a
      specific autoimmune subgroup of SSc.

PMID- 16802364
TI  - Induction of apoptosis and fibrillin 1 expression in human dermal endothelial
      cells by scleroderma sera containing anti-endothelial cell antibodies.
AB  - OBJECTIVE: Sera from patients with scleroderma (systemic sclerosis [SSc]) contain
      anti-endothelial cell antibodies (AECAs) capable of inducing endothelial cell
      apoptosis. We sought to determine whether SSc sera containing anticentromere
      antibodies (ACAs) or anti-topoisomerase I antibodies (or, anti-Scl-70 antibodies)
      contain subsets of AECAs that trigger distinct pathways of apoptosis and gene
      expression in normal adult human dermal endothelial cells (HDECs). METHODS: Adult
      HDECs were grown to subconfluence and treated with control or SSc patient sera.
      Apoptosis was investigated by differential interference contrast (DIC)
      microscopy, microarrays of proapoptotic gene expression, caspase 3 protease
      activity, and flow cytometry for phosphatidyl serine translocation. RESULTS: Flow
      cytometry and DIC microscopy demonstrated that HDECs exposed to SSc sera
      containing either SSc autoantibody underwent apoptosis at much higher levels than
      those treated with control sera. While unique gene expression profiles were
      induced in HDECs by stimulation with SSc sera containing the respective
      autoantibody, similar patterns of increased gene expression of transcripts for
      the proapoptotic protease caspase 3 as well as the SSc autoantigen fibrillin 1
      were demonstrated. Caspase 3 gene expression correlated with increased protease
      activity, and targeted inhibition of this protease partly blocked SSc serum
      induced apoptosis. Immunohistochemistry studies of serum-stimulated HDECs
      demonstrated the aberrant expression of fibrillin 1 protein only in apoptotic
      endothelial cells treated with SSc sera containing AECAs. CONCLUSION: There are
      distinct AECA subsets in the sera of patients with limited SSc (with ACAs) and
      diffuse SSc (with anti-Scl-70) that induce unique patterns of HDEC gene
      expression in the setting of apoptosis associated with increased caspase 3
      activity and the reexpression of endothelial cell fibrillin 1.

PMID- 16802365
TI  - Hemorheologic profile in systemic sclerosis: role of NOS3 -786T > C and 894G >T
      polymorphisms in modulating both the hemorheologic parameters and the
      susceptibility to the disease.
AB  - OBJECTIVE: Microvascular disorders are relevant in systemic sclerosis (SSc).
      Hyperviscosity, due to alterations of blood cells and plasma components, may play
      a role in the pathogenesis of microcirculatory disorders. An impaired
      availability of nitric oxide, related to polymorphisms in NOS3, the gene for
      endothelial cell nitric oxide synthase, might influence erythrocyte
      deformability. We undertook this study to investigate the hemorheologic profile
      in SSc and the role of NOS3 polymorphisms in modulating the hemorheologic status
      of SSc patients. METHODS: We studied 113 consecutive SSc patients (75 with
      limited cutaneous SSc [lcSSc] and 38 with diffuse cutaneous SSc [dcSSc]) and 113
      healthy controls. The hemorheologic profile was obtained by assessing whole blood
      viscosity (WBV; at shear rates of 0.512 and 94.5 seconds(-1)), plasma viscosity
      (PLV; at a shear rate of 94.5 seconds(-1)), and erythrocyte deformability index
      (DI). We determined NOS3 polymorphisms by molecular analysis. RESULTS: A marked
      alteration of hemorheologic parameters was found both in patients with lcSSc and
      in those with dcSSc compared with controls (P < 0.0001). In multivariate
      analysis, rheologic variables were significantly associated with the disease (for
      WBV at a shear rate of 94.5 seconds(-1), odds ratio [OR] 5.4, 95% confidence
      interval [95% CI] 1.4-19.9, P = 0.01; for PLV, OR 2.8, 95% CI 1.2-6.5, P = 0.01;
      for DI, OR 3.9, 95% CI 1.4-10.8, P = 0.007), and NOS3 -786C and 894T alleles
      significantly affected the DI (for -786C allele, OR 2.3, 95% CI 1.01-5.4, P =
      0.04; for 894T allele, OR 2.2, 95% CI 1.01-4.8, P = 0.04). The simultaneous
      presence of the -786C and 894T alleles represented a susceptibility factor for
      SSc (OR 2.8, 95% CI 1.4-5.7, P = 0.004). CONCLUSION: Our findings document an
      altered rheologic profile in SSc and demonstrate a relationship between this
      alteration and NOS3 polymorphisms, thus shedding light on a potential novel
      mechanism influencing the microcirculation in this disease.

PMID- 16802366
TI  - Association between enhanced type I collagen expression and epigenetic repression
      of the FLI1 gene in scleroderma fibroblasts.
AB  - OBJECTIVE: Scleroderma (systemic sclerosis; SSc) is an autoimmune disease
      characterized by vasculopathy and widespread organ fibrosis. Altered fibroblast
      function, both in vivo and in vitro, is well documented and illustrated by
      augmented synthesis and deposition of extracellular matrix proteins. We undertook
      this study to investigate the possibility that epigenetic mechanisms mediate the
      emergence and persistence of the altered SSc fibroblast phenotype. METHODS: The
      effects of DNA methyltransferase and histone deacetylase inhibitors on collagen
      expression and the level of epigenetic mediators in fibroblasts were examined.
      The effects of transient transfection of SSc fibroblasts with FLI1 gene and
      normal cells with FLI1 antisense construct on collagen expression were
      determined. The methylation status of the FLI1 promoter was tested in cultured
      cells and in SSc and normal skin biopsy specimens. RESULTS: Increased levels of
      epigenetic mediators in SSc fibroblasts were noted. The addition of epigenetic
      inhibitors to cell cultures normalized collagen expression in SSc fibroblasts.
      The augmented collagen synthesis by SSc fibroblasts was linked to epigenetic
      repression of the collagen suppressor gene FLI1. Heavy methylation of the CpG
      islands in the FLI1 promoter region was demonstrated in SSc fibroblasts and skin
      biopsy specimens. CONCLUSION: The results of this study indicate that epigenetic
      mechanisms may mediate the fibrotic manifestations of SSc. The signal
      transduction leading to the SSc fibrotic phenotype appears to converge on DNA
      methylation and histone deacetylation at the FLI1 gene.

PMID- 16802367
TI  - Identification of transitional type II B cells in the salivary glands of patients
      with Sjogren's syndrome.
AB  - OBJECTIVE: To identify B cell subpopulations participating in the lymphocyte
      infiltrate of salivary glands from patients with primary Sjogren's syndrome. A
      special emphasis was placed on those B lymphocytes included in the ectopic
      germinal centers (GCs). METHODS: The presence of B cells in salivary glands and
      their polyclonality were ascertained by phenotyping and reverse transcription
      polymerase chain reaction in salivary gland samples from 18 patients. Their
      phenotype was thoroughly analyzed using a number of double-staining combinations.
      The results obtained in tissue sections were confirmed by fluorescence-activated
      cell sorting analysis of B cells eluted from salivary glands, and these findings
      were compared with those in tonsils. RESULTS: Memory-type B cells were defined as
      CD20+, CD27+ and were seen in all specimens, whereas GCs were found in only 7
      specimens. Furthermore, B cells found in these GCs lacked certain characteristics
      of centroblasts and centrocytes. Instead, they fulfilled the criteria for
      transitional type II (TII) B cells and resembled marginal-zone B cells. BAFF (the
      assistance of which is required for proper transformation of transitional TI B
      cells into transitional TII B cells) accumulated adjacent to transitional and
      marginal-zone-like B lymphocytes. Further evidence for the involvement of BAFF
      came from the expression of its receptors on infiltrating B cells. CONCLUSION:
      These transitional TII and marginal-zone-like B cells are probably instrumental
      in the local production of autoantibodies and possibly influential in the ensuing
      destruction of epithelial cells.

PMID- 16802368
TI  - Increased extracellular levels of the novel proinflammatory cytokine high
      mobility group box chromosomal protein 1 in minor salivary glands of patients
      with Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the expression of the novel proinflammatory cytokine
      high mobility group box chromosomal protein 1 (HMGB-1) in the salivary glands of
      patients with Sjogren's syndrome (SS) and patients with sicca symptoms. METHODS:
      Biopsy samples from the minor labial salivary glands of patients with SS,
      patients with sicca symptoms but no diagnosis of SS, and healthy controls were
      investigated. Expression of HMGB-1, tumor necrosis factor (TNF), and interleukin
      1beta (IL-1beta) was analyzed using immunohistochemical staining on consecutive
      cryosections. RESULTS: Increased expression of HMGB-1 was observed among the
      large infiltrates of mononuclear cells found in biopsy samples from patients with
      SS, and the degree of extracellular HMGB-1 was significantly higher in patients
      with SS compared with patients with sicca symptoms and with healthy controls (P <
      0.05 and P < 0.01, respectively). Cellular expression of TNF was increased in
      patients with SS and in patients with sicca symptoms. In addition, the level of
      secreted TNF was significantly higher in patients with SS than in healthy
      controls (P < 0.05). Intracellular expression of IL-1beta was detected in all
      groups, while extracellular IL-1beta was observed almost exclusively among the
      infiltrating mononuclear cells of patients with SS. CONCLUSION: The increased
      amount of extracellular HMGB-1 observed in salivary glands of patients with SS
      indicates that HMGB-1 is involved in the inflammatory process of the disease.
      This cytokine, along with TNF and IL-1beta, may form a proinflammatory loop that
      promotes the chronic features of the glandular inflammation in SS.

PMID- 16802369
TI  - Salivary gland epithelial cells: a new source of the immunoregulatory hormone
      adiponectin.
AB  - OBJECTIVE: Adiponectin is an adipocytokine that displays insulin-sensitizing and
      immunoregulatory properties. Adipocyte development in association with fibrosis
      is frequently detected in primary Sjogren's syndrome lesions, connoting a healing
      process. The aim of this study was to examine the expression of adiponectin in
      minor salivary gland biopsy specimens obtained from patients with primary SS and
      controls. METHODS: The expression of adiponectin in minor salivary gland biopsy
      specimens and in long-term-cultured non-neoplastic salivary gland epithelial cell
      (SGEC) lines obtained from patients with primary SS and control subjects was
      examined, using immunohistochemistry and immunoblotting, respectively. The
      expression of adiponectin, adiponectin receptor 1 (AdipoR1), and AdipoR2
      messenger RNA (mRNA) by SGECs was investigated by reverse transcription
      polymerase chain reaction. RESULTS: Immunohistochemical analysis for adiponectin
      revealed positive staining of adipocytes from primary SS lesions as well as
      ductal epithelial cells from both patients with primary SS and controls. All of
      the SGEC lines tested were shown to express adiponectin, AdipoR1, and AdipoR2
      mRNA, whereas adiponectin protein expression was detected by immunoblotting in
      SGECs from patients with primary SS but not in those from controls. The analysis
      of concentrated culture supernatants also revealed increased adiponectin
      expression by SGECs from patients with SS compared with controls. CONCLUSION: Our
      findings provide novel evidence that adiponectin is produced by SGECs. The high
      constitutive expression of adiponectin by SGECs from patients with primary SS is
      likely attributable to aberrant activation of these cells. Although the
      significance of adiponectin expression remains unknown, it is possible that
      adiponectin functions in an autocrine manner, as suggested by concurrent
      expression of the relevant receptors.

PMID- 16802370
TI  - Impaired salivary gland function in NOD mice: association with changes in
      cytokine profile but not with histopathologic changes in the salivary gland.
AB  - OBJECTIVE: To characterize the chronologic disease course and possible
      interrelationships between salivary gland inflammation, hyposalivation, and
      cytokine levels in NOD mice, a model for Sjogren's syndrome (SS). METHODS: NOD
      mice of different ages were used to mimic different disease stages of SS.
      Histopathologic findings and rates of salivary secretion were compared between 8
      week-old, 17-week-old, and 24-week-old female mice. In addition, 10 cytokines
      were analyzed in serum and saliva obtained from NOD and BALB/c mice. RESULTS: In
      NOD mice, the salivary flow rate did not change between 8 weeks and 17 weeks of
      age, while a significant decrease in the salivary flow rate occurred between 17
      weeks and 24 weeks of age (P < 0.001). In contrast, significant histopathologic
      changes in the salivary glands occurred before 17 weeks of age. Chronic
      inflammatory cell infiltrates were characterized by T and B cell infiltration.
      Interestingly, in one-third of the mice, proliferating cells were observed in the
      focal infiltrates. Significant changes in the levels of interleukin-2 (IL-2), IL
      5, and granulocyte-macrophage colony-stimulating factor in serum, and in the
      levels of IL-4 and tumor necrosis factor alpha (TNFalpha) in saliva occurred
      contemporarily with the decrease in salivary flow. Correlation analyses revealed
      a negative association between salivary secretion and the levels of IL-4,
      interferon-gamma, and TNFalpha in saliva obtained from NOD mice, while the
      correlation with inflammatory changes in the glands was consistently weak.
      CONCLUSION: Consistent with previous findings, our results indicate at least 2
      phases of SS-like disease in NOD mice. Hyposalivation was preceded by
      inflammatory changes in the salivary glands, whereas abrupt changes in secretion
      occurred without significant progression of inflammation. Changes in cytokine
      levels are an indication of the mechanisms involved in the adaptive immune
      response in the transition from early to overt disease.

PMID- 16802371
TI  - Manipulation of isoprenoid biosynthesis as a possible therapeutic option in
      mevalonate kinase deficiency.
AB  - OBJECTIVE: In cells from patients with the autoinflammatory disorder mevalonate
      kinase (MK) deficiency, which includes the hyperimmunoglobulin D with periodic
      fever syndrome, MK becomes the rate-limiting enzyme in the isoprenoid
      biosynthesis pathway. This suggests that up-regulation of residual MK activity in
      these patients could be a way in which to prevent or alleviate the associated
      symptoms. We studied the effect of 2 specific inhibitors of isoprenoid
      biosynthetic enzymes on the residual activity of MK in cells from patients with
      MK deficiency. METHODS: Skin fibroblasts from MK-deficient patients and from
      controls were cultured for 7 days with either simvastatin, an inhibitor of 3
      hydroxy-3-methylglutaryl coenzyme A reductase, or zaragozic acid A, an inhibitor
      of squalene synthase. Following culture, MK activity, MK protein levels, MVK
      messenger RNA levels, and the effect on the pathway flux toward non-sterol
      isoprenoid biosynthesis were determined. RESULTS: Treatment of the fibroblasts
      with either of the inhibitors led to a marked increase in residual MK enzyme
      activity, which was largely attributable to increased MVK gene transcription.
      This effect was even more pronounced when the cells were cultured in lipoprotein
      depleted medium. The flux toward nonsterol isoprenoid end-product synthesis was
      reduced when cells were treated with simvastatin but was partly restored by
      concomitant treatment with zaragozic acid A. CONCLUSION: Our results indicate
      that manipulations of the isoprenoid biosynthesis pathway that promote the
      synthesis of nonsterol isoprenoids may provide an interesting therapeutic option
      for the treatment of MK deficiency.

PMID- 16802372
TI  - A severe case of chronic infantile neurologic, cutaneous, articular syndrome
      treated with biologic agents.
AB  - In this report we describe a case of severe chronic infantile neurologic,
      cutaneous, articular (CINCA) syndrome with a novel G307V cryopyrin mutation and
      all of the characteristic clinical and laboratory features of this
      autoinflammatory disease. There was no clear response to standard therapies,
      including human interleukin-1 (IL-1) receptor antagonist (anakinra) and soluble
      tumor necrosis factor receptor (etanercept). The patient finally had a partial
      clinical response (reduction in fever and irritability) and complete laboratory
      response (improved C-reactive protein and serum amyloid A levels) to humanized
      anti-IL-6 receptor antibody (MRA), but died from congestive heart failure and
      interstitial pneumonia 2 months after initiation of therapy. We serially measured
      the serum cytokine levels and expression of NF-kappaB activation in the patient's
      peripheral blood mononuclear cells before and during consecutive therapies.
      Pathologic examination of autopsy specimens was also performed. This case
      illustrates the continued difficulty in management of patients with CINCA
      syndrome and the complexity of the inflammatory pathways in this disorder.

PMID- 16802373
TI  - Antigenic targets and pathogenicity of anti-aortic endothelial cell antibodies in
      Takayasu arteritis.
AB  - OBJECTIVE: Anti-endothelial cell antibodies are considered to have an important
      role in the pathogenesis of Takayasu arteritis (TA). Previously, these antibodies
      were detected using human umbilical vein endothelial cells, which do not
      completely represent the antigenicity/functions of aortic endothelial cells, the
      specific targets in TA. To delineate the precise role of antigenic targets, we
      investigated such targets as well as the pathogenic mechanism of antibodies
      directed against aortic endothelial cells (AAECAs) in TA. METHODS: AAECAs were
      detected using a cellular enzyme-linked immunosorbent assay (ELISA), and their
      antigenic targets were detected by immunoblotting. AAECA-mediated induction of
      endothelial adhesion molecule expression and cytokine production was studied by
      ELISA, and apoptosis was studied using the TUNEL method. RESULTS: AAECAs were
      detected in 86% of patients with TA and in 9% of controls. Sera obtained from
      AAECA-positive patients with TA recognized a total of 9 antigens ranging in size
      from 18 kd to 200 kd, of which the 60-65-kd triplet was recognized most often.
      The aortic endothelial cell reactivity of Hsp60-absorbed sera was reduced by
      approximately 50% as compared with that of unabsorbed sera (mean +/- SD 0.488 +/-
      0.08 versus 0.838 +/- 0.116). Sera from AAECA-positive patients with TA, compared
      with sera from AAECA-negative patients with TA and that from controls, induced
      increased expression of E-selectin (mean +/- SD 0.833 +/- 0.063 versus 0.217 +/-
      0.081 and 0.221 +/- 0.101 optical density [OD] units, respectively) and vascular
      cell adhesion molecule 1 (0.620 +/- 0.144 versus 0.165 +/- 0.005 and 0.177 +/-
      0.055 OD units, respectively) and increased production of interleukin-4 (IL-4)
      (6.8 +/- 2.4 versus 1.2 +/- 1.6 and 1.3 +/- 2.5 pg/ml, respectively), IL-6 (24.3
      +/- 2.4 versus 4.5 +/- 6.7 and 5.9 +/- 5.1 pg/ml, respectively), and IL-8 (36.8
      +/- 10.3 versus 10.1 +/- 6.7 and 7.8 +/- 2.1 pg/ml, respectively). Sera from
      AAECA-positive patients with TA induced 29 +/- 6% (median +/- SEM) apoptosis of
      aortic endothelial cells. CONCLUSION: Our data show that the AAECAs that are
      present in patients with TA are directed mainly against 60-65-kd antigen(s) and
      may cause vascular dysfunction by inducing expression of endothelial adhesion
      molecules, cytokine production, and apoptosis.

PMID- 16802374
TI  - Association of intermittent hydrarthrosis with MEFV gene mutations.

PMID- 16802375
TI  - Concomitant interferon-alpha therapy and tumor necrosis factor alpha inhibition
      for rheumatoid arthritis and hepatitis C.

PMID- 16802376
TI  - How should best strategy and tight control be translated into clinical practice?
      Comment on the article by Goekoop-Ruiterman et al.

PMID- 16802378
TI  - Clinical significance of the long-term symptom-modifying effects of glucosamine
      sulfate: comment on the article by Brandt and Mazzuca.

PMID- 16802380
TI  - Usefulness of the British Isles Lupus Assessment Group index in pediatric
      clinical trials: comment on the article by Ruperto et al.

PMID- 16802381
TI  - B cell therapy with the anti-CD22 monoclonal antibody epratuzumab: comment on the
      editorial by St. Clair and Tedder.

PMID- 16802383
TI  - Cortisol secretion and symptoms in patients with fibromyalgia: comment on the
      article by McLean et al.

PMID- 16802384
TI  - Further support for the statins as antiinflammatory and immunomodulatory agents:
      comment on the review by Abeles and Pillinger and the editorial by Arnaud and
      Mach.

PMID- 16802385
TI  - Possible role of tick-borne infection in "cat-scratch disease": comment on the
      article by Giladi et al.

PMID- 16802387
TI  - Subtle myelin defects in PLP-null mice.
AB  - This study explores subtle defects in the myelin of proteolipid protein (PLP)
      null mice that could potentially underlie the functional losses and axon damage
      known to occur in this mutant and in myelin diseases including multiple
      sclerosis. We have compared PLP-null central nervous system (CNS) myelin with
      normal myelin using ultrastructural methods designed to emphasize fine
      differences. In the PLP-null CNS, axons large enough to be myelinated often lack
      myelin entirely or are surrounded by abnormally thin sheaths. Short stretches of
      cytoplasm persist in many myelin lamellae. Most strikingly, compaction is
      incomplete in this mutant as shown by the widespread presence of patent
      interlamellar spaces of variable width that can be labeled with ferricyanide,
      acting as an aqueous extracellular tracer. In thinly myelinated fibers,
      interlamellar spaces are filled across the full width of the sheaths. In thick
      myelin sheaths, they appear filled irregularly but diffusely. These patent spaces
      constitute a spiral pathway through which ions and other extracellular agents may
      penetrate gradually, possibly contributing to the axon damage known to occur in
      this mutant, especially in thinly myelinated fibers, where the spiral path length
      is shortest and most consistently labeled. We show also that the "radial
      component" of myelin is distorted in the mutant ("diagonal component"), extending
      across the sheaths at 45 degrees instead of 90 degrees. These observations
      indicate a direct or indirect role for PLP in maintaining myelin compaction along
      the external surfaces of the lamellae and to a limited extent, along the
      cytoplasmic surfaces as well and also in maintaining the normal alignment of the
      radial component.

PMID- 16802388
TI  - The conformations of alkanes adsorbed on zeolitic cations.

PMID- 16802389
TI  - Single-molecule dynamic triangulation.
AB  - A proposal for using single molecules as nanoprobes capable of detecting the
      trajectory of an elementary charge is discussed in detail. Presented numerical
      simulations prove that this single-molecule technique allows determination of a
      three-dimensional single-electron displacement within a few seconds with an
      accuracy better than 0.006 nm. Surprisingly, this significantly exceeds the
      accuracy with which the probe molecule itself can be localized (given the same
      measuring time) by means of single-molecule microscopy. It is also shown that the
      optimal concentration of probe molecules in the vicinity of the electron (i.e.
      the concentration which provides the best accuracy of the inferred electron
      displacement) is of the order of 10(-5) m.

PMID- 16802390
TI  - Diels-Alder reactions are faster in water than in ionic liquids at room
      temperature.

PMID- 16802391
TI  - Efficient construction of the clerodane decalin core by an asymmetric Morita
      Baylis-Hillman reaction/Lewis acid promoted annulation strategy.

PMID- 16802392
TI  - Ruthenium-catalyzed propargylic reduction of propargylic alcohols with silanes.

PMID- 16802393
TI  - The roles of hydrogen bonding and sterics in RNA interference.

PMID- 16802394
TI  - Dinuclear double-stranded metallosupramolecular ruthenium complexes: potential
      anticancer drugs.

PMID- 16802395
TI  - Total synthesis of (+/-)-symbioimine.

PMID- 16802396
TI  - Generalized fabrication of multifunctional nanoparticle assemblies on silica
      spheres.

PMID- 16802397
TI  - Asymmetric heterogeneous catalysis.
AB  - Limited natural resources and an increasing demand for enantiomerically pure
      compounds render catalysis and especially heterogeneous asymmetric catalysis a
      key technology. The field has rapidly advanced from the initial use of chiral
      biopolymers, such as silk, as a support for metal catalysts to the modern
      research areas. Mesoporous supports, noncovalent immobilization, metal-organic
      catalysts, chiral modifiers: many areas are rapidly evolving. This Review shows
      that these catalysts have more to them than facile separation or recycling.
      Better activities and selectivities can be obtained than with the homogeneous
      catalyst and novel, efficient reaction mechanisms can be employed. Especially
      fascinating is the outlook for highly ordered metal-organic catalysts that might
      allow a rational design, synthesis, and the unequivocal structural
      characterization to give tailor-made catalysts.

PMID- 16802398
TI  - Multiple length-scale patterning of DNA by stamp-assisted deposition.

PMID- 16802399
TI  - Bioconjugated Ag nanoparticles and CdTe nanowires: metamaterials with field
      enhanced light absorption.

PMID- 16802400
TI  - Fatty acid-induced effect on glucagon secretion is mediated via fatty acid
      oxidation.
AB  - BACKGROUND: While the effect of fatty acids and ectopic triglyceride storage in
      pancreatic beta cells has been well-defined, only limited information is
      available on alpha cells. This study evaluates the long-term impact of fatty
      acids on alpha cell function and proliferation as well as fatty acid oxidation.
      METHODS: Clonal alpha cells were cultured with fatty acids in the presence of
      high glucose for up to 3 days. The influence of fatty acids on glucagon
      secretion, glucagon content and triglyceride accumulation from 24 to 72 h was
      investigated. After a - 72 h culture, cell proliferation, carnitine palmitoyl
      transferase-1 mRNA level and the effect of etomoxir were also elucidated.
      RESULTS: Fatty acids stimulated glucagon secretion and increased triglyceride
      accumulation in a time- and dose-dependent manner, but inhibited alpha cell
      proliferation. Lower concentrations (0.125-0.25 mM) of fatty acids significantly
      increased glucagon secretion at 48 and 72 h, but did not affect triglyceride
      content. However, a marked increment in triglyceride accumulation occurred in the
      presence of 0.5 mM fatty acids. Fatty acids caused an up-regulation of the
      expression of carnitine palmitoyl transferase-1 gene. Etomoxir (1 microM)
      reversed fatty acid-induced glucagon hypersecretion, but did not inhibit
      carnitine palmitoyl transferase-1 mRNA level. CONCLUSIONS: Our data indicates
      that compared with triglyceride accumulation, glucagon secretion is more
      sensitive to changes in fatty acid concentration. The effect of fatty acids on
      the glucagon response is mediated through their oxidation. The high carnitine
      palmitoyl transferase-1 gene expression and the accumulation of triglyceride may
      initially be a compensatory oxidation reaction to elevated fatty acids.

PMID- 16802401
TI  - Cancer-specific targeting of an adenovirus-delivered herpes simplex virus
      thymidine kinase suicide gene using translational control.
AB  - Two technical hurdles, gene delivery and target specificity, have hindered the
      development of effective cancer gene therapies. In order to circumvent the
      problem of tumor specificity, the suicide gene, HSV-1 thymidine kinase (HSV-Tk),
      was modified with a complex 5' upstream-untranslated region (5'-UTR) that limits
      efficient translation to cells expressing high levels of the translation
      initiation factor, eIF4E. Since previous studies have shown that most tumor cells
      express elevated levels of eIF4E, tumor-specific gene delivery was optimized by
      incorporation of the 5'-UTR-modified suicide gene (HSV-UTk) into an adenovirus
      vector (Ad-CMV-UTk). The efficacy of this novel approach of targeting suicide
      gene expression and limiting cytotoxicity by means of translational restriction
      was tested in vitro with the use of the human breast cancer cell lines (MCF-7,
      MDA-MB435, and ZR-75-1). As controls, normal MCF10A, HMEC, and HMSC cell lines
      that express relatively low levels of eIF4E were used. Real-time reverse
      transcription polymerase chain reaction (RT-PCR) was used to quantify HSV-Tk mRNA
      for cells infected with Ad-CMV-UTk as well as with Ad-CMV-Tk (a control
      adenovirus in which HSV-Tk is not regulated at the level of translation).
      Translation of HSV-Tk in the Ad-infected cells was measured by Western blot
      analysis. In addition, cytotoxicity was determined following treatment with the
      pro-drug ganciclovir (GCV) using an MTT viability assay. Finally, microPET
      imaging was used to assess cancer cell-specific expression of HSV-Tk and
      expression in normal tissues in vivo after intraperitoneal injection of Ad-CMV-Tk
      or Ad-CMV-UTk. These data collectively showed enhanced cancer cell-specific gene
      expression and reduced normal tissue gene expression for the Ad-HSV-UTk compared
      to the Ad-CMV-Tk, leading to increased cancer cell-enhanced GCV cytotoxicity.
      These results indicate that translational targeting of suicide gene expression in
      tumor cells in vitro and in vivo is effective and may provide a platform for
      enhanced cancer gene therapy specificity.

PMID- 16802402
TI  - UK doctors' anger over NHS cash crisis.

PMID- 16802403
TI  - Peru's epidemiological transition.

PMID- 16802404
TI  - A rapidly convergent series for calculation of the interaction between two
      similar plane double-layers for z+/z- = -2 asymmetric electrolytes at positive
      surface potential.
AB  - A rapidly convergent series for calculation of the interaction energies between
      two similar plane double-layers for z+/z- = -2 asymmetric electrolytes at
      positive surface potential are obtained by introducing a parameter lambda in
      elliptical integral. When dimensionless surface potential is less or equal to 20,
      the number of the series terms required to obtain the interaction energies with
      six significant digits are not more than 4. The accurate numeral results are
      given and they can be used to check up the validity of approximate expressions
      people obtain. The present results are also fit for z+/z- = -1/2 asymmetric
      electrolytes at negative surface potential.

PMID- 16802405
TI  - Whither medical botany?

PMID- 16802407
TI  - [Respiratory medicine and new techniques].

PMID- 16802408
TI  - [Biology and physiology].

PMID- 16802409
TI  - [Epidemiology].

PMID- 16802410
TI  - [Addiction to smoking].

PMID- 16802411
TI  - [Respiratory infections].

PMID- 16802412
TI  - [Asthma].

PMID- 16802413
TI  - [Chronic obstructive pulmonary disease].

PMID- 16802414
TI  - [Diffuse infiltrative lung diseases].

PMID- 16802415
TI  - [Lung diseases in children].

PMID- 16802416
TI  - [Thoracic oncology].

PMID- 16802417
TI  - [Development of a short version of the Insecurity Questionnaire (U-Bogen-24) by
      Ullrich & Ullrich de Muynck].
AB  - The psychometric properties of a newly developed short version of the
      "Unsicherheitsfragebogen" (Insecurity Questionnaire) by Ullrich & Ullrich de
      Muynck are examined using data drawn from a nationally representative survey of
      652 former East and 1283 former West Germans. In addition, the questionnaire was
      tested on a clinical sample of 318 psychotherapy inpatients. The study
      demonstrates good test-theoretical features regarding parameters of items and
      subscales. In the population sample woman score higher on subscales fear of
      criticism and incapacity in saying NO and lower on scale being able to demand.
      Female psychotherapy patients score higher on scale fear of criticism and lower
      on scale being able to demand than male psychotherapy patients. When comparing
      psychotherapy patients to the population sample with respect to gender, male and
      female psychotherapy patients score higher on scales fear of criticism, fear of
      contact and incapacity in saying NO and lower on scale being able to demand.
      Scale means as reference values for the population sample as well as for the
      psychotherapy patients are reported.

PMID- 16802418
TI  - [Duration of inpatient depression treatment--fair benchmarking between
      hospitals].
AB  - Process and outcome quality of inpatient treatment of depression in Germany was
      described in a multicenter study of 10 hospitals in North-Rhine Westphalia, Baden
      Wurttemberg and Bavaria. The treatment of more than 2000 depressive patients was
      assessed by quality indicators and outcome was compared between the hospitals
      (benchmarking). Results show great variance in length of stay between the
      hospitals. While in one hospital patients with depressive episodes were
      discharged after 36.8 days (average), the average length of stay in another
      hospital was 64.3 days. Furthermore the study revealed that hospitals differ
      strongly regarding their case-mix. Using stepwise multiple regression analyses
      potential confounding variables (sociodemographics, history of previous
      treatment, severity of depression) were identified and their influence on length
      of stay was calculated. After cross validation the regression analyses model
      explained 7% of the variance and included 5 predictors. Length of stay is
      prolonged by patients with a recurrent depressive disorder, by patients with
      impairment of social functioning and by severity of the depression. Length of
      stay is reduced if the indication of inpatient treatment was crisis intervention
      and if there was a previous suicide attempt. It was shown that differences in
      patient case-mix only account for a small percentage of hospital differences in
      length of stay. Method, effort and benefit of the regression analyses approach
      are discussed.

PMID- 16802419
TI  - [E-mail in psychotherapy--an aftercare model via electronic mail for
      psychotherapy inpatients].
AB  - We introduce an aftercare program for psychotherapy inpatients, which is based on
      regular communication via E-mail. The organizational and operational structure of
      the program are described within the context of computer mediated communication.
      First results on utilization and acceptance are reported. In comparison to
      patients who did not participate in either aftercare program of the clinic, the E
      mail participants are younger and higher educated. Inpatient treatment of the
      participants was three days shorter in duration than that of non participants.
      Both groups were similar with regard to symptom distress at discharge from
      hospital. A low dropout rate of 8%, the high activity and satisfaction emphasize
      the positive acceptance of the program. Therapists' E-mail activity turned out to
      be important for the participants. Neither age, internet experience or symptom
      related variables nor the own E-mail activity were associated with participants'
      evaluation of the new service. Based on these first positive experiences the
      perspectives of using E-mail in psychotherapy will be discussed.

PMID- 16802420
TI  - [The relevance of personality and sexual traumata for sexual offenders in
      forensic psychiatry].
AB  - BACKGROUND: Studies in forensic psychiatry indicate that persons in prison and
      psychologically disturbed sexual offenders have a high degree of traumatic
      experiences. But less is known about other specific risk factors. The aim of this
      study was to investigate the extent to which the diagnoses and traumata of sexual
      offenders differ from those of non-sexual offenders. METHOD: 51-male, German,
      forensic psychiatric patients were examined. Various self-evaluation
      questionnaires served to ascertain dissociative and general psychopathology and
      interpersonal problems. RESULTS: No significant correlations were found between
      sexual offences and forensic or socio-demographic variables. Nor was it possible
      to identify any differences in dissociative and psychopathological factors
      between sexual offenders and non-sexual offenders. However, the comparison
      between these groups showed that the former more frequently reported sexual abuse
      in their biographies and the diagnosis more frequently indicated a narcissistic
      personality disorder. But the logistic regression analysis coupled with age
      pointed to only sexual abuse in childhood as a significant factor. CONCLUSION:
      Our data support the idea that one's own traumatic experiences are reproduced
      later. That indicates the significance of dealing with traumatic experiences in
      childhood for this group of offenders.

PMID- 16802421
TI  - [Sleeping problems and attachment quality in toddlers].
AB  - The study presented addresses the association between 18-months-olds' attachment
      quality and subsequent sleeping problems at 30 months. The sample consisted in 62
      healthy, firstborn children and their primary caregivers. Attachment quality was
      assessed using Ainsworths' Strange Situation Procedure. Sleeping disorders were
      diagnosed conducting a standardized psychiatric interview with the mothers.
      Securely attached toddlers showed sleeping problems more often than insecurely
      avoidant attached ones. Attachment disorganization was not related to sleeping
      problems. Analyzing the impact of self-stimulation behavior (i.e. thumb or
      pacifier sucking) it could be demonstrated that all 30-months-olds who showed
      self-stimulating behavior were insecurely-avoidant attached to their primary
      caregiver. Thus, insecure-avoidant toddlers might incline to suppress attachment
      behavior and negative emotions when being separated from parent in the evening
      and night hours.

PMID- 16802422
TI  - [Psychiatric disorders of environmental outpatients--results of the standardized
      psychiatric interview (CIDI) from the German multi-center study on Multiple
      Chemical Sensitivity (MCS)].
AB  - BACKGROUND: A nationwide, environmental outpatient-based multi-center two-phase
      study on Multiple Chemical Sensitivity (MCS) was conducted from 1999 until 2004.
      The aim of the study was to characterize more precisely the health-complaints
      relevant for the MCS-phenomenon. A standardized psychiatric interview (CIDI),
      used to identify frequency, character and duration of psychiatric disorders and
      their chronological relation to the environment-related health complaints of the
      patients, formed part of the extensive diagnostic procedure. METHOD: 251 (86.3%)
      of the 291 attendees of the environmental outpatient departments in Aachen,
      Berlin, Bredstedt, Freiburg, Giessen and Munich, were examined using the German
      version (M-CIDI/DIA-X) of the Composite International Diagnostic Interview.
      RESULTS: 83.7% (lifetime prevalence rate) fulfilled the diagnostic criteria of at
      least one psychiatric disorder, with the 12-month and 4-week prevalence rates
      being 76.5% and 64.5%, respectively. Environmental outpatients, in all prevalence
      periods, had significantly higher rates of psychiatric disorders than the
      comparable general population. Somatoform disorders were most frequently
      diagnosed, followed by depressive and phobic disorders. For 81.2% of the patients
      the psychiatric disorder started long before the environment-related health
      complaints (average 17 years). CONCLUSIONS: This study confirms the results of
      earlier studies, i.e. that patients with environment-related health complaints
      suffer from psychiatric disorders more frequently than the general population.
      The high environmental outpatients really suffer from psychosomatic complaints,
      but attribute the causes to the environment. Application of specific therapeutic
      regimen is recommended for those patients, whose psychiatric disorders are
      safeguarded diagnostically and for whom a relevant exposure is unlikely.

PMID- 16802423
TI  - [Validation and standardization of the "Questionnaire for Assessing Subjective
      Physical Well-Being" by Kolip and Schmidt in a representative German sample].
AB  - The "Questionnaire for Assessing Subjective Physical Well-Being" by Kolip and
      Schmidt is examined using data drawn from a nationally representative survey of
      573 former East and 1900 former West Germans. In this non-clinical sample the
      construct "subjective physical well-being" assessed by the "Questionnaire for
      Assessing Subjective Physical Well-Being" seems to have just one dimension. As
      women and probands with growing age score lower for "subjective physical well
      being" a differentiated standardization was done for gender and age. Connections
      between "subjective physical well-being" and body-image assessed by the "Body
      Image Questionnaire" (FKB-20), quality of life ("EURO-HIS-QOL"), and questions
      for concerns about financial situation, family and health give hints for validity
      of the questionnaire.

PMID- 16802424
TI  - [Post-traumatic Stress Disorder: history of a politically unwanted diagnosis].
AB  - Severe psychological responses to war and violence were already described in
      Greek antiquity. However, an officially acknowledged diagnosis was introduced
      only as recently as 1980. This paper describes the historical development of the
      diagnosis "Posttraumatic Stress Disorder", and investigates why it took so long
      for the diagnosis to be officially accepted. A first concept goes back to the
      London Surgeon Eric Erichsen, who in 1866 developed the influential hypotheses
      that psychological symptoms after railway accidents were caused by a concussion
      of the spine followed by "molecular changes" in the spinal cord ("railway spine
      syndrome"). At the same time, Pierre Janet and Sigmund Freud investigated the
      aetiology of hysteria. In World War I and II, up to 10% of the soldiers were
      exempted from further service because they suffered from nervous breakdowns
      caused by the experience of war ("shell shock"). Insights into the psychological
      long-term effects of Nazi Germany's concentration camps, the political activities
      of the Vietnam Veterans, and evidence from clinical studies resulted in the
      introduction of the newly defined diagnosis "Post-traumatic Stress Disorder" into
      DSM-III in 1980. In the past few years, several aspects of this diagnostic
      concept were legitimately criticized. Nevertheless, the official introduction of
      the diagnosis led to the acknowledgement of personal suffering and to the
      development of specific and efficacious therapies.

PMID- 16802425
TI  - [Abdominal infection: surgical domain].

PMID- 16802426
TI  - [Revision of the G-DRG system exemplified by proximal femoral fractures].

PMID- 16802427
TI  - [Typical performance of the established physician].

PMID- 16802428
TI  - [Revision of the (model) occupational regulation for physicians].

PMID- 16802429
TI  - [Legal decision for monetary compensation due to lack of team involvement.
      Judgment of the Lower Saxony Medical Court of 17 November 2004 - BG 17/02].

PMID- 16802430
TI  - [Brief report of the Hamburg Area Society].

PMID- 16802431
TI  - [Report on the work of the Brandenburg Area Society].

PMID- 16802432
TI  - [Report on the membership meeting of the Westphalia Area Society of BDC 19
      October 2005].

PMID- 16802433
TI  - [Report on the 19th Annual Surgeon Day].

PMID- 16802434
TI  - [Principle statement of the German Association of Specialist Medical Societies.
      Enduring safety of specialist medical care with a high quality level].

PMID- 16802435
TI  - [Malpractice risk of the physician. Unawareness does not protect from penalty-
      safety is more important than ever].

PMID- 16802436
TI  - [Day for Physicians. "The federal 'stinginess is proud' mentality has already
      produced enough damage"].

PMID- 16802437
TI  - Expanding role of MR angiography in clinical practice.
AB  - MRA has higher accuracy, less operator dependence, a larger field-of-view, three
      dimensionality and superior contrast resolution than ultrasonography.
      Additionally, MRA offers a safer alternative to the patient than CTA as neither
      ionizing radiation nor iodinated contrast agents are used. Contrast-enhanced MRA
      with extra cellular contrast agents is fast and flow-independent, offers
      substantially higher spatial and temporal resolution compared to non-contrast
      techniques and has become the standard of practice. The highly accurate but
      static anatomical road-map thus generated can be supplemented with time-resolved
      MRA and blood flow measurement techniques for a more comprehensive assessment of
      systemic vascular disease. In the context of burgeoning technological advances
      with rapid translation into clinical MRA practice, this review explores the
      current position of MRA and the potential role for the new and exciting blood
      pool contrast agents for diagnosing and characterizing vascular disease. Blood
      pool agents offer the potential to take MRA to the next level by combining first
      pass arterial phase imaging with steady state high-resolution images that exploit
      the persistent high intravascular enhancement generated by blood-pool agents and
      which is significantly greater than with extra cellular agents. Additional
      benefits derive from the ability to characterize plaque and to detect internal
      bleeding. These advantages place MRA in a prime position to comprehensively and
      non-invasively evaluate both vascular anatomy and function with anticipated
      further expansion into more and more clinical applications.

PMID- 16802438
TI  - Vasovist-enhanced MR angiography.
AB  - Vasovist (MS-325) is the first intravascular contrast agent approved for use with
      magnetic resonance angiography in the European Union. Vasovist reversibly binds
      to albumin, providing extended intravascular enhancement compared to existing
      extracellular magnetic resonance contrast agents. Prior to approval, Vasovist
      underwent extensive testing to evaluate the safety and efficacy of the drug; the
      clinical trials program included blinded, placebo-controlled dose ranging,
      efficacy in a variety of vascular beds (AIOD, renal, pedal), examination of
      potential drug interaction with warfarin and comparison with XRA. The clinical
      trials show that Vasovist-enhanced MR angiography is safe and well-tolerated in
      patients with vascular disease, effective for the detection of vascular stenosis
      and aneurysms, significantly more accurate (both more sensitive and specific)
      than non-contrast MR angiography for the diagnosis of vascular stenoses, and
      similar to conventional angiography for the overall characterization of vascular
      disease, without the need for catheterization.

PMID- 16802439
TI  - Initial imaging recommendations for Vasovist angiography.
AB  - Vasovist is a newly developed blood pool contrast agent for MR angiogiography
      (MRA). It consists of a low molecular weight molecule, chelated to Gadolinium,
      that strongly binds to plasma proteins, thus increasing its relaxivity and
      retention time in the vascular system. Due to its high efficiency, a smaller dose
      compared to existing Extracellular Fluid Contrast Agents is sufficient for
      diagnostic purposes, resulting in a lower injection volume. With appropriate
      adjustments of standard extracellular contrast injection protocols, a dynamic
      phase MRA can be achieved using routine MRA parameters. For extended phase
      imaging, ('steady-state') starting approximately 3 to 5 min post injection,
      repetition time (TR) and flip angle may be adjusted for optimization of
      intravascular signal. Preliminary technical recommendations for the optimization
      of contrast-enhanced MRA with Vasovist can be deducted from current clinical
      trial experience in various vessel beds.

PMID- 16802440
TI  - Mind the gap.

PMID- 16802441
TI  - German firms resort to consolidation to restore glory days.

PMID- 16802442
TI  - Chemistry outsourcing going global.

PMID- 16802443
TI  - Anti-obesity therapies.

PMID- 16802444
TI  - Inhaled human insulin.

PMID- 16802445
TI  - Changes in the welfare caseload and the health of low-educated mothers.
AB  - Declines in the welfare caseload in the late 1990s brought significant change to
      the lives of many low-educated, single mothers. Many single mothers left welfare
      and entered the labor market and others found different ways to avoid going on
      public assistance. These changes may have affected the health and health
      behaviors of these women. To date, there has been little study of this issue. In
      this paper, we obtained estimates of the association between changes in the
      welfare caseload caused by welfare policy, and four health behaviors--smoking,
      drinking, diet, and exercise--and four self-reported measures of health--weight,
      days in poor mental health, days in poor physical health, and general health
      status. The results of our study reveal that recent declines in the welfare
      caseload were associated with less binge drinking, but otherwise welfare reform
      had little effect on health and health behaviors.

PMID- 16802446
TI  - [The 48th annual meeting of the Japanese Society of Child Neurology.  Chiba,
      Japan. June 1-3, 2006. Program and Abstracts].

PMID- 16802447
TI  - [The 47th annual meeting of the Japanese Society of Neuropathology.  Okayama,
      Japan. May 24-26, 2006. Program and Abstracts].

PMID- 16802448
TI  - [The 48th Congress of the Japanese Geriatric Society. Kanazawa, Japan. June 7-9,
      2006. Abstracts].

PMID- 16802449
TI  - Analytical challenges in molecular electronics.

PMID- 16802450
TI  - Affinity-based strategies for protein purification.

PMID- 16802451
TI  - Quiz page. Arterial-venous fistulas from kidney biopsies.

PMID- 16802452
TI  - Update of the editorial governance plan for JAMA.

PMID- 16802453
TI  - Adsorption and oxidation of aniline and anisidine by chromium ferrocyanide.
AB  - The interaction of aniline and p-anisidine with chromium ferrocyanide has been
      studied. Maximum uptake of both anilines was observed around pH 7. The adsorption
      data obtained at neutral pH were found to follow Langmuir adsorption. Anisidine
      was a better adsorbate because of its higher basicity. In alkaline medium (pH>8)
      both aniline and anisidine reacted with chromium ferrocyanide to give colored
      products. Analysis of the products by GC-MS showed benzoquinone and azobenzene as
      the reaction products of aniline while p-anisidine afforded a dimer. IR analysis
      of the amine-chromium ferrocyanide adduct suggests that the outer metal ion of
      chromium ferrocyanide and amino group of amines are responsible for the
      interaction. A possible reaction mechanism for the product formation in alkaline
      medium has been proposed. The present study suggests that metal ferrocyanides
      might have played an important role in the stabilization of organic molecules
      through their surface activity in the prebiotic condensation reactions.

PMID- 16802456
TI  - Phase behavior of polyglycerol didodecanoates in water.
AB  - A phase diagram of a water-polyglyceryl didodecanoate ((C11)2Gn) system was
      constructed as a function of polyglycerol chain length (n) at 25 degrees C. The
      average number of dodecanoic acid residues attached to polyglycerol is in the
      range of 1.6-2.3, and unlike commercial long-chain polyglycerol surfactants,
      unreacted polyglycerols were removed in the surfactants used. With an increase in
      the polyglycerol chain, the surfactant changes from lipophilic to hydrophilic,
      and the type of self-organized structure also changes from lamellar liquid
      crystals to the aqueous micellar solution phase via hexagonal liquid crystals.
      However, a discontinuous micellar cubic phase does not appear in the phase
      diagram, while it is formed in a long poly(oxyethylene)-chain nonionic surfactant
      system. In a dilute region, a cloud point is observed at a moderate polyglycerol
      chain length, n approximate to 7. The cloud temperature is dramatically increased
      with a slight increase in hydrophilic chain because the dehydration of the
      hydrophilic chain length at high temperature is low compared with that of the
      poly(oxyethylene) chain. In other words, the phase behavior of (C11)2Gn is not
      very temperature sensitive. Three-phase microemulsion is formed in a
      water/(C11)2.3G7.3/m-xylene system. The three-phase temperature or HLB
      temperature is highly dependent on the polyglycerol chain length.

PMID- 16802457
TI  - Pesticides in cigarette smoke.

PMID- 16802458
TI  - Microfluidic IEF without carrier molecules.

PMID- 16802459
TI  - Gel electrophoresis and MEKC join forces on chip.

PMID- 16802460
TI  - Methylphenols removal from water by low-cost adsorbents.
AB  - A comparative study on the adsorption of methylphenols on adsorbents prepared
      from several industrial wastes has been carried out. The results show that extent
      of adsorption on carbonaceous adsorbent prepared from fertilizer industry waste
      has been found to be 37.3, 40.5, 65.9, and 88.5 mg/g for 2-methylphenol, 4
      methylphenol, 2,4-dimethylphenol, and 2,4,6-trimethylphenol, rspectively. As
      compared to carbonaceous adsorbent, the other three adsorbents viz. blast furnace
      sludge, dust, and slag adsorb methylphenols to a much smaller extent. This has
      been accounted for due to the carbonaceous adsorbent having a larger porosity and
      consequently higher surface area. The adsorption of phenols on this carbonaceous
      adsorbent as a function of contact time, concentration, and temperature has been
      studied by the batch method. The adsorption has been found to be endothermic and
      data conform to the Langmuir equation. The analysis of data indicates that
      adsorption is a first-order process and pore diffusion-controlled. The efficiency
      of the carbonaceous adsorbent was assessed by comparing the results with those on
      a standard activated charcoal sample. It was found that the carbonaceous
      adsorbent is about 45% as efficient as standard activated charcoal and can
      therefore be employed for the removal of methylphenols from wastewaters.

PMID- 16802461
TI  - Unraveling the mystery of the solar system.

PMID- 16802463
TI  - Building microfluidic devices one drop at a time.

PMID- 16802462
TI  - The new era of SAW devices. Commercial SAW sensors move beyond military and
      security applications.

PMID- 16802464
TI  - Ionic liquids in analytical chemistry.

PMID- 16802466
TI  - Village tensions in early Virginia: sex, land, and status at the Neck of Land in
      the 1620s.

PMID- 16802467
TI  - The dynamics of health insurance coverage: 1996 to 2000.

PMID- 16802468
TI  - Current awareness on yeast.

PMID- 16802469
TI  - Medicine in colonial America.  [Review of: Reiss, O.  Medicine in colonial
      America.  Lanham, Md.: U. Pr. of America, 2000].

PMID- 16802470
TI  - Drug diplomacy in the twentieth century: an international history.  [Review of:
      McAllister, W.B.  Drug diplomacy in the twentieth century: an international
      history.  New York: Routledge, 2000].

PMID- 16802471
TI  - Dietary sodium intake and its relation to human health: a summary of the
      evidence.

PMID- 16802472
TI  - Teaching sex: the shaping of adolescence in the 20th century.  [Review of: Moran,
      J.P.  Teaching sex: the shaping of adolescence in the 20th century.  Cambridge,
      Mass.: Harvard U. Pr., 2000].

PMID- 16802473
TI  - Committed to the state asylum: insanity and society in nineteenth-century Quebec
      and Ontario.  [Review of: Moran, J.E.  Committed to the state asylum: insanity
      and society in nineteenth-century Quebec and Ontario.  Montreal: McGill-Queen's
      U. Pr., 2000].

PMID- 16802474
TI  - Doing good: the life of Toronto's General Hospital.  [Review of: Connor, J.T.H. 
      Doing good: the life of Toronto's General Hospital.  Toronto: U. of Toronto Pr.,
      2000].

PMID- 16802475
TI  - A social contract for the coal fields: the rise and fall of United Mine Workers
      of America Welfare and Retirement Fund.  [Review of: Mulcahy, R.P.  A social
      contract for the coal fields: the rise and fall of United Mine Workers of America
      Welfare and Retirement Fund.  Knoxville: U. of Tennessee Pr., 2000].

PMID- 16802476
TI  - Authorized to heal: gender, class, and the transformation of medicine in
      Appalachia, 1880-1930.  [Review of: Barney, S.L.  Authorized to heal: gender,
      class, and the transformation of medicine in Appalachia, 1880-1930.  Chapel Hill:
      U. of North Carolina Pr., 2000].

PMID- 16802477
TI  - Clean living movements: American cycles of health reform.  [Review of: Engs, R.C.
      Clean living movements: American cycles of health reform.  Westport, Conn.:
      Praeger, 2000].

PMID- 16802478
TI  - Chlorpyrifos: ecological risk assessment in North American aquatic environments.

PMID- 16802479
TI  - Muscle relaxants--atracurium and other recent developments.

PMID- 16802480
TI  - Safety in anaesthesia.

PMID- 16802481
TI  - Fluid deficits and hypotension during colonoscopy.

PMID- 16802482
TI  - Data linkage enables evaluation of long-term survival after intensive care.
AB  - Outcomes of intensive care are important to the patient and for assessment of
      benefit. Short-term outcomes after critical illness are well described, but less
      is known about long-term outcomes. This study describes the use of data linkage,
      combining intensive care unit (ICU) clinical data with administrative morbidity
      and mortality data, to assess long-term outcomes after treatment in ICU. The
      hospital-based cohort study was conducted in a 22-bed general ICU in a
      metropolitan teaching hospital. All patient admissions admitted to ICU from 1
      January 1987 to 31 December 2002 were included. The prospective ICU clinical
      database with patient demographics, ICU diagnoses, severity of illness, daily
      assessment of organ failures and common daily treatments used was linked using
      probabilistic methods to the state-wide hospital morbidity and mortality
      databases to describe long-term survival. There were 26,019 ICU admissions
      (22,980 patients) with 25,972 records (99.8%) linked to a hospitalization event
      that included the index ICU admission. Unadjusted survival was 84.7% at 1 year
      decreasing progressively to 50.7% at 15 years. Age, type of admission, severity
      of illness (measured by Acute Physiologic and Chronic Health Evaluation (APACHE)
      II and the presence of organ failure), ICU length of stay, comorbidity (Chronic
      Health Evaluation and Charlson comorbidity index) and ICU admission diagnosis,
      were all associated with survival at 1, 3, 5, 10, and 15 year follow-up (P<0.001
      at all time points). Linkage of clinical and administrative data provides a
      feasible method for ascertaining long-term survival after critical illness. Age,
      admission severity of illness, diagnosis and comorbidity influenced long-term
      unadjusted survival.

PMID- 16802483
TI  - Intravenous fluid to prevent hypotension in patients undergoing elective
      colonoscopy.
AB  - Colonoscopy may be associated with hypotension during sedation leading to
      postoperative morbidity. However, no treatment is proven to ameliorate
      intraoperative hypotension for this procedure. We therefore conducted a
      randomized trial to determine the effect of intravenous fluid infusion on the
      incidence of hypotension during sedation for colonoscopy. With institutional
      approval, 160 patients presenting for elective colonoscopy were randomized to 1.5
      ml/kg or 15 ml/kg Hartmann's solution before colonoscopy. All observers were
      blind to group allocation. The incidence of hypotension during sedation (29% vs
      25%; P=0.59) and postoperative morbidity (nausea, vomiting, headache, drowsiness
      and dizziness) (41% vs 39%; P= 0.75) did not differ between the two groups.
      Hypotensive patients were older, had a higher baseline systolic blood pressure,
      and were thirstier after fluid infusion than normotensive patients. This study
      does not support the use of 15 ml/kg Hartmann's solution to reduce the incidence
      of hypotension or postoperative morbidity in patients undergoing elective
      colonoscopy.

PMID- 16802484
TI  - A pilot study to test the use of a checklist in a tertiary intensive care unit as
      a method of ensuring quality processes of care.
AB  - This pilot study aimed to test the use of a checklist as a method of ensuring
      that certain processes of care are performed routinely and systematically in a
      tertiary intensive care unit. The pilot involved the development of a process
      indicator checklist, its implementation and review. The checklist contained 16
      items sourced from the literature or deemed important by local clinicians.
      Checklists were completed on the morning round for all adult patients admitted to
      the unit for approximately one month. Baseline and evaluation surveys were
      conducted with medical staff to assess both the benefits and shortcomings of
      using the checklist. Results demonstrated good compliance in completing the
      checklist (81%) and that when checked, certain aspects of care were not always
      delivered when appropriate. At the conclusion of the study the majority of
      medical staff believed that care in the intensive care unit actually improved
      with the use of the checklist, and all thought that it assisted in ensuring that
      good quality care was delivered. The checklist is a useful tool that can be
      readily applied to facilitate best practice and quality in everyday clinical
      care, ultimately leading to better health outcomes for patients.

PMID- 16802485
TI  - Positive end-expiratory pressure ventilation increases extravascular lung water
      due to a decrease in lung lymph flow.
AB  - Positive end-expiratory pressure (PEEP) is used to improve gas exchange, increase
      functional residual capacity, recruit air spaces, and decrease pulmonary shunt in
      patients suffering from respiratory failure. The effect of PEEP on extravascular
      lung water (EVLW), however, is still not fully understood. This study was
      designed as a prospective laboratory experiment to evaluate the effects of PEEP
      on EVLW and pulmonary lymph flow (QL) under physiologic conditions. Twelve adult
      sheep were operatively prepared to measure haemodynamics of the systemic and
      pulmonary circulation, and to assess EVLW In addition, the lung lymphatic duct
      was cannulated and a tracheostomy performed. The animals were then mechanically
      ventilated in the awake-state without end-expiratory pressure (PEEP 0). After a
      two-hour baseline period, PEEP was increased to 10 cmH2O for the duration of two
      hours, and then reduced back to 0 cmH2O. Cardiopulmonary variables, QL, and
      arterial blood gases were recorded intermittently; EVLW was determined two hours
      after each change in PEEP. The increase in PEEP resulted in a decrease in QL (7
      +/- 1 vs 5 +/- 1 ml/h) and an increase in EVLW (498 +/- 40 vs 630 +/- 58 ml;
      P<0.05 each) without affecting cardiac output. As PEEP was decreased back to
      baseline, QL increased significantly (5 +/- 1 vs 10 +/- 2 ml/h), whereas EVLW
      returned back to baseline. This study suggests that institution of PEEP produces
      a reversible increase in EVLW that is linked to a decrease in QL.

PMID- 16802486
TI  - Skin temperature during sympathetic block: a clinical comparison of bupivacaine
      0.5% and ropivacaine 0.5% or 0.75%.
AB  - Measurement of skin temperature can be used as an indicator of sympathetic
      blockade induced by neuraxial anaesthesia. The aim of the study was to test the
      skin temperature response to epidural administration of bupivacaine and different
      concentrations of ropivacaine. Forty-eight ASA class I-II patients undergoing
      herniorraphy were enrolled into a prospective, randomized, double-blind clinical
      trial. Patients were randomly allocated to receive epidural anaesthesia with a
      single dose of 18 ml of bupivacaine 0.5% (n=16); ropivacaine 0.5% (n=16), or
      ropivacaine 0.75% (n=16). A temperature probe was positioned on the skin of the
      thigh and skin temperature registered before epidural anaesthesia, every 10
      minutes for the first hour after the epidural injection and every hour for the
      following four hours. Sensory blockade was assessed by pinprick and motor
      blockade using the Bromage scale. No significant difference was observed in
      sensory or motor blockade. A skin temperature rise of 1 to 1.8 degrees C compared
      with basal values was observed in all patients within the first hour. Temperature
      returned to basal values within four hours in the ropivacaine 0.5% group, within
      five hours in the ropivacaine 0.75% group, and remained 1 degrees C higher after
      five hours in the bupivacaine 0.5% group (P<0.01). The duration of sympathetic
      block is significantly shorter with ropivacaine than with bupivacaine.

PMID- 16802487
TI  - Recovery after prolonged anaesthesia for acoustic neuroma surgery: desflurane
      versus isoflurane.
AB  - In this study, 33 patients were randomly assigned to receive desflurane (D) or
      isoflurane (I) for acoustic neuroma surgery. The time from end of the procedure
      to spontaneous breathing, extubation, eye-opening, hand-squeezing to command, and
      ability to state name, birthdate and phone number were recorded. The Steward
      recovery score was also recorded every five minutes during the first 20 minutes
      postoperatively and then every 10 to 15 minutes. Groups were similar regarding
      patient characteristics, depth of anaesthesia, sufentanil total dose, anaesthesia
      duration (D: 349.1 +/- 19.1 min; I: 349.2 +/- 22.9 min), haemodynamic/respiratory
      parameters, and surgical conditions (assessed by a bleeding score). The emergence
      time in the D group was significantly faster than the I group (D: 14.9 +/- 2.4
      min vs I: 29.2 +/- 2.4 min for eye-opening). Full recovery also occurred earlier
      in the D group (D: 22.1 +/- 3.1 min vs I: 37.6 +/- 4.0 min, P<0.005 for stating
      name). Steward recovery scores were also better during the first postoperative
      hour in the D group (D: 40 min vs I: 90 min, P<0.005 for 100% of patients with
      Steward score of 6). The results indicate that desflurane is associated with
      similar operating conditions and faster postoperative recovery following acoustic
      neuroma surgery. The faster recovery following desflurane may be desirable after
      long surgical procedures, enabling the patient's full cooperation and
      facilitating early diagnosis of any potential neurological deficit.

PMID- 16802488
TI  - Protein contamination of the Laryngeal Mask Airway and its relationship to re
      use.
AB  - The Laryngeal Mask Airway is a reusable device for maintaining the patency of a
      patient's airway during general anaesthesia. The device can be reused after it
      has been cleaned and sterilized. Protein contamination of medical instruments is
      a concern and has been found to occur despite standard sterilization techniques.
      The reason for the concern relates to the possibility of the transmission of
      prions and the risk of developing a neurodegenerative disorder such as
      Creutzveldt-Jacob disease. The purpose of this study was to quantify the amount
      of protein contamination that occurs, and to relate this to the number of times
      the Laryngeal Mask Airway has been used. Fifty previously used Classic Laryngeal
      Masks were collected after routine sterilization and packaging. The devices were
      immersed in protein detecting stain and then visual inspection performed to
      assess the degree and distribution of the staining. The researcher was blinded to
      the number of times the Laryngeal Mask Airway had been used. Linear regression
      analysis of the degrees of staining of the airway revealed that protein
      contamination occurs after the first use of the device and this increases with
      each subsequent use. This finding highlights the concern that the currently used
      cleaning and sterilization methods do not prevent the accumulation of
      proteinaceous material on Laryngeal Mask Airways. Consideration should be given
      to the search for more efficient cleaning and sterilization techniques or the use
      of disposable devices.

PMID- 16802489
TI  - 10,000 reasons to step out--exercise patterns and pedometer evaluation of
      consultant anaesthetists.
AB  - Major international bodies recommend that adults should accumulate at least 30
      minutes of moderate intensity physical activity every day. Ten thousand steps a
      day has been found to approximate 30 minutes of exercise. A questionnaire
      regarding exercise patterns was sent to all (584) Victorian consultant
      anaesthetists, and 30 consultants wore a pedometer for one week, during working
      hours only. The questionnaire response rate was 59.4% (347). Of these
      respondents, 58% indicated that they had a formal exercise program. There were no
      significant differences between people with a set exercise program and those
      without, with respect to age, gender, working hours or smoking. Those with a set
      exercise program exercised a median of four times per week and the commonest
      exercise listed was gymnasium attendance (40%). The main reasons cited for having
      a regular exercise program were maintenance of physical health (77%), mental
      health (71%) and weight control (35%). The main reasons for not having an
      exercise program were fatigue (40%), too busy (70%), family commitments (67%) or
      just not interested (18%). The overall median steps per day for the pedometer
      group was 4770 with a range of 1667 to 9630, fitting into the classification of
      'sedentary'. In summary this study has shown that a significant number of
      anaesthetists do not achieve adequate physical activity in or out of working
      hours and has identified some reasons for this behaviour. This will hopefully
      provide motivation and information for the implementation of useful strategies to
      increase the level of physical activity performed by anaesthetists.

PMID- 16802490
TI  - Comparison of remifentanil and fentanyl in anaesthesia for elective
      cardioversion.
AB  - This prospective, randomized, double-blind study was designed to compare the
      recovery characteristics of remifentanil and fentanyl in combination with
      propofol for direct current cardioversion. Patients undergoing elective
      cardioversion received either intravenous fentanyl 1 microg/kg (n=33) or
      remifentanil 0.25 microg/kg (n=30) and propofol was titrated to a Ramsay sedation
      score of 5 by slow intravenous injection. Heart rate, systolic, diastolic and
      mean blood pressures decreased significantly following sedation in both groups
      but did not show a significant difference between the groups. Time to answer a
      question (306 +/- 83 vs 383 +/- 131s, mean +/- SD, P=0.014) and time to sit up
      (412 +/- 90 vs 511 +/- 126s, P=0.002) were significantly shorter in the
      remifentanil group compared to the fentanyl group. Side-effects and patient
      discomfort were similar for both groups. Remifentanil can be used as a suitable
      supplement to propofol for direct current cardioversion and may provide a faster
      recovery profile than fentanyl.

PMID- 16802491
TI  - Patients' understanding of pre-operative fasting.
AB  - We aimed to assess elective day surgery patients' understanding of the reason for
      pre-operative fasting. One hundred adult patients presenting to the peri
      operative unit for day procedures requiring general anaesthesia were surveyed
      before discharge. All day-stay, adult patients able to complete a questionnaire
      in English were included. Only 22% (95%CI [14,31]) of patients correctly
      understood why fasting was necessary. Patients who did not understand were nearly
      five times more likely to underrate the importance of compliance (risk ratio
      4.65, 95%CI [1.2,18]). Two per cent (95%CI [0.2,7]) of patients reported actual
      non-compliance, and 4% (95%CI [1,10]) stated they would consider misrepresenting
      their fasting status if it was inconvenient for them to have their surgery
      postponed. The results of this study suggest a need to better inform day surgery
      patients about the reason for pre-operative fasting. A better understanding of
      the need for pre-operative fasting may lead to improved compliance and patient
      safety.

PMID- 16802492
TI  - Propofol EDTA and reduced incidence of infection.
AB  - Propofol formulated in a lipid vehicle supports the growth of microorganisms.
      There have been worldwide reports of extrinsic microbial contamination of
      propofol leading to outbreaks of serious postoperative nosocomial infections.
      Therefore it is essential that medical professionals follow strict aseptic
      precautions when handling propofol, as recommended by manufacturers of propofol
      and the Centers for Disease Control and Prevention. Non-adherence to these
      recommendations increases the risk of nosocomial postoperative infections, which
      impose a heavy burden of morbidity and mortality and have serious economic
      consequences. It has also been recommended that the use of EDTA-containing
      formulations of propofol be considered. In vitro studies have confirmed that EDTA
      added to propofol retards microbial growth. Data on the incidence of nosocomial
      infections before and after the introduction of propofol with EDTA indicates that
      there have been no further cluster outbreaks and individual nosocomial infections
      appear to have been reduced. The addition of EDTA is an additional safety
      precaution to good aseptic practice.

PMID- 16802493
TI  - Mixed opioid--mixed message?
AB  - By exposing the mu-receptor (MOP-R) to more than one exogenous ligand, the
      administration during general anaesthesia of more than one opioid with principal
      action on the receptor may confound and lead to complications or unexpected
      outcomes. The giving of such a 'mixed message' can result in respiratory
      depression, excess sedation and delayed recovery to an unusual degree. We present
      a case of apparent extreme opioid sensitivity and discuss a possible mechanism.
      Such occurrences may be more common than previously realised.

PMID- 16802494
TI  - Anaesthetic management of a patient with relapsing polychondritis undergoing
      laparoscopic surgery.
AB  - We describe the anaesthetic management of a patient with relapsing polychondritis
      who underwent laparoscopic cholecystectomy. We failed to secure a patent airway
      with a ProSeal laryngeal mask airway, probably because of the deformity of the
      larynx. The glottis was small and it was only possible to pass a 5.5 mm cuffed
      endotracheal tube into the trachea. Positive pressure ventilation with 5 cm H2O
      positive end-expiratory pressure and surgery were safely performed. In relapsing
      polychondritis, recurrent inflammation and destruction of laryngeal and
      tracheobronchial cartilage causes airway obstruction, and various sizes of
      tracheal tubes and other airway manipulation devices should be prepared.

PMID- 16802495
TI  - Use of recombinant activated factor VII after axillofemoral bypass grafting.
AB  - Recombinant activated factor VII (rFVIIa) is a powerful prohaemostatic agent that
      theoretically predisposes to thrombosis after peripheral vascular surgery. We
      report the use of rFVIIa to reduce bleeding in a patient after axillofemoral
      bypass grafting for ruptured aorto-iliac pseudoaneurysm. Despite the increased
      risk of thrombosis, the patient made an uneventful recovery with preserved graft
      patency. The favourable result suggests that rFVIIa should be considered even in
      vascular surgical patients, if the risks of continued bleeding outweigh those of
      thrombosis. Better risk estimation is only possible if reports of rFVIIa use in
      vascular patients continue to appear and through controlled trials.

PMID- 16802496
TI  - Upper airway obstruction caused by ingestion of concentrated acetic acid.
AB  - We report a case of rapidly progressive severe upper airway obstruction in a
      small child caused by accidental ingestion of 80% acetic acid. Emergency
      cricothyrotomy was necessary after both endotracheal intubation and bag-valve
      mask ventilation were not possible. Although intubation was eventually achieved,
      a tracheostomy was necessary. Toxin spilled over the anterior chest and abdomen
      caused third degree skin burns which required grafting. Mild liver dysfunction
      was observed. Complete recovery occurred.

PMID- 16802497
TI  - Development of bilateral herpes zoster following thoracoscopic splanchnicectomy.
AB  - A 39-year-old female presented for elective bilateral thoracoscopic
      splanchnicectomy for chronic severe visceral pain. Surgery and anaesthesia were
      uneventful and she gained good symptomatic relief. Postoperative recovery was
      complicated by the development on day four of bilateral herpes zoster at the T8
      dermatome level. This was treated immediately with oral acyclovir. She
      subsequently developed severe post-herpetic neuralgia requiring the
      recommencement of gabapentin and amitriptyline. Further benefit was gained from a
      course of calcitonin. This case report examines the possible causative factors in
      the development of post-surgical herpes zoster.

PMID- 16802498
TI  - Cricothyroidotomy: a short-term measure for elective ventilation in a patient
      with challenging neck anatomy.
AB  - Cricothyroidotomy is a well established technique of airway management in
      emergency situations where translaryngeal intubation cannot be achieved. This
      case report describes a case where cricothyroidotomy was used for elective
      ventilation for short period of 48 hours in a patient who had a vocal cord palsy,
      supraglottic oedema and inflammation. Surgical tracheostomy was considered the
      preferred option, but this was deemed impossible due to the challenging neck
      anatomy in this case.

PMID- 16802499
TI  - Systemic capillary leak syndrome associated with compartment syndrome and
      rhabdomyolysis.
AB  - Systemic capillary leak syndrome (SCLS) is a rare disorder characterized by
      recurrent spontaneous episodes of hypovolaemic shock due to marked plasma shifts
      from the intravascular to the extravascular space. This presents as the
      characteristic triad of hypotension, haemoconcentration and hypoalbuminemia often
      with an associated monoclonal gammopathy. We describe a patient with SCLS who
      required aggressive fluid resuscitation and emergency fasciotomies for
      compartment syndrome with rhabdomyolysis. At presentation the patient was
      considered to have severe erythrocytosis and was therefore initially referred to
      a haematologist, which appears to be a frequent sequence of presentation for
      patients with SCLS. This patient also highlights the importance of muscle
      compartment pressure monitoring during volume resuscitation in patients with
      SCLS.

PMID- 16802500
TI  - A serious and repeatable electrical hazard--compressed electrical cord and an
      operating table.
AB  - We describe a previously unreported hazard resulting from compression of an
      electrical cable by an operating theatre table. This resulted in a live wire
      contact to the operating table. Intermittent connection of the table to earth
      during a procedure resulted in triggering of a residual current device mitigating
      the effects of the hazard. The actual cause was not readily identified as the
      devices connecting the table to earth were considered most likely to be the
      source of the current. There was potential for significant injury to the patient
      and theatre staff which would have been diminished if staff had had a better
      understanding of the electrical safety equipment in use. We examine the
      underlying causes of the accident, discuss electrical safety and correct use of
      safety devices in the operating theatre, and propose guidelines for appropriate
      management.

PMID- 16802501
TI  - Enhancement of pulse oximeter plethysmographic waveform in a patient with
      Takayasu's arteritis.

PMID- 16802502
TI  - Simplified format of cardiac risk stratification: assisting the physician in
      decision-making.

PMID- 16802503
TI  - Anaesthesia for neurosurgery in sitting position.

PMID- 16802504
TI  - Mivacurium in multicore disease.

PMID- 16802505
TI  - The utility of fluoroscopic guidance in thoracic epidural placement.

PMID- 16802506
TI  - [Arterial hypertension 2: Secondary forms of arterial hypertension].

PMID- 16802507
TI  - [Echocardiographic analysis in cardiac amyloidosis].
AB  - Systemic amyloidosis with cardiac involvement may clinically be suspected in the
      presence of heart failure or arrhythmia of unknown origin. Herein two cases of
      cardiac amyloidosis are described with a clinical presentation of heart failure
      refractory to usual treatment. The key role of echocardiography in the diagnosis
      and prognosis evaluation of cardiac amyloidosis is discussed. A treatment
      targeted against the generation of amyloid fibril should ideally be initiated
      before apparition of heart failure.

PMID- 16802508
TI  - [Systemic sclerosis and cancer].
AB  - The combination of skin induration with clinical features such as dyspnea, facial
      telangiectasia, digital infarctions and/or dysphagia supports the diagnosis of
      systemic sclerosis. The oesophageal dysmotility is associated with symptoms which
      may delay the diagnosis of gastro-oesophageal cancer. Herein we report a case of
      long standing systemic sclerosis with heartburn and dysphagia symptoms which were
      monitored closely. Unfortunately, these symptoms delayed the diagnosis of gastric
      adenocarcinoma. This case prompted us to review the evidence of the association
      of cancer and systemic sclerosis and if any oncologic evaluation is required
      during the follow-up of patients affected with systemic sclerosis.

PMID- 16802510
TI  - [Microscopic polyangiitis: an unusual case report].
AB  - A 56-year-old woman was referred to our hospital because persistence of fever and
      inflammatory syndrome after antibiotic treatment for pneumonia. In the past, no
      special feature. Physical examination revealed only--at first--a pneumonia. Two
      weeks after, associated with the cough, she developed an acute renal failure. The
      laboratory revealed an inflammatory syndrome associated with proteinuria,
      hematuria and anti-neutrophil cytoplasmic antibodies. The CT of thorax shows
      aspecific infiltrations. The renal biopsy, in the context of the patient,
      diagnosed an microscopic polyangiitis. All the symptom resolved with the
      initiation of corticoid and cyclophosphamide treatment.

PMID- 16802512
TI  - [Introduction to the 180th Rhine-Westphalia Society of Internal Medicine e.V.
      Dusseldorf 24-26 November 2005].

PMID- 16802513
TI  - [Thoughts on the current status of medical education].

PMID- 16802514
TI  - [Hypertension and heart].
AB  - The term hypertensive heart disease covers the entities left ventricular
      hypertrophy, microangiopathy, diastolic and systolic dysfunction, und increased
      risk of arrhythmias. From the pathophysiological point of view this is caused by
      hypertrophy of cardiac myocytes, interstitial fibrosis and media hypertrophy of
      the arterioles. As an earliest sign of hypertensive heart disease a
      microangiopathy can be diagnosed. Also a diastolic dysfunction can be found as an
      early change. In further persisting arterial hypertension left ventricular
      hypertrophy develops (often asymmetric), and later a systolic dysfunction.
      Clinically, the patients suffer from angina pectoris, dyspnea and rhythm
      disorders. Left ventricular hypertrophy is associated with an increased risk of
      ventricular malignant arrhythmias. Thus, the main therapeutic principle should be
      antihypertensive therapy with the goal of regression of hypertrophy and, as a
      consequence, a decreased mortality risk.

PMID- 16802515
TI  - [Cardiac disease in patients with tumors and tumor therapy].
AB  - Cardiac disease may occur as direct complications of heart tumors or indirect
      complications of malignancies related to antineoplastic therapy. While primary
      cardiac neoplasias are rare, metastases to various cardiac structures are common.
      Cardiac tumors may cause a wide variety of clinical signs and symptoms. Benign
      myxomas are the most common primary tumors and often can be cured by total
      excision. Nearly all primary cardiac malignancies are sarcomas with a poor
      prognosis. The cardiotoxicity of anticancer agents can lead to significant
      complications that can affect patients being treated for various noncardiac
      neoplasias. Cancer treatment, most frequently anthracyclines, but also
      trastuzumab, cyclophosphamide and others may compromise cardiac function. The
      severity of such toxicity depends on many factors such as the molecular site of
      action, the immediate and cumulative dose, the method of administration, the
      presence of any underlying cardiac condition, and the patient's demographics.
      Moreover, toxicity can be affected by current or previous treatment with other
      antineoplastic agents or by concomitant irrradiation. Cardiotoxic effects can
      occur immediately during administration of the drug, or they may not manifest
      themselves until months or years after the patient has been treated. Radiation
      ports that include the heart may produce late coronary artery disease or
      constrictive pericarditis. Since cardiovascular disease and cancer are both
      common, precise knowledge of therapeutic interactions and complications is
      warranted.

PMID- 16802516
TI  - [Myocardial disease in viral infections. Myocarditis--cardiomyopathy].
AB  - Inflammation of the myocardium is a common cardiac disease. Molecular and
      immunhistological techniques help to assure myocarditis in terms of persistence
      of chronic viral infection and myocardial inflammation activity. The connection
      between viral myocarditis and development of dilative cardiomyopathy is of great
      interest. Thus, new possibilities arise for assessment of the disease prognosis
      and the strategy of specific immunosuppressive, immunomodulating and antiviral
      therapy.

PMID- 16802517
TI  - [Cardiac manifestations of rheumatic diseases].
AB  - Inflammatory rheumatic diseases potentially involve organs and structures far
      beyond the musculoskeletal system including skin and blood vessels. A broad
      spectrum of neurologic, renal, pulmonary, hematologic and cardiac manifestations
      contributes to the complex clinical picture of connective tissue diseases and
      vasculitides. Regarding cardiac disease all structures of the heart may be
      involved. 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 better
      long-term prognosis in connective tissue diseases, cardiovascular complications
      as a consequence of chronic disease- and therapy-related damage gain increasing
      attention.

PMID- 16802518
TI  - [Sequels of lung diseases on cardiac function].
AB  - The most severe cardiac sequel of lung diseases is the load of the right
      ventricle due to pulmonary hypertension with the development of a cor pulmonale.
      This is characterized by hypertrophy and/or dilatation of the right ventricle
      because of a primary impairment of lung function and/or lung structure. The most
      important pathomechanisms of the development of pulmonary hypertension are vessel
      obliteration, mechanical lesions, primary vascular or extravascular inflammation
      and hypoxic vasoconstriction. Chronic obstructive pulmonary disease (COPD) is one
      of the most important reasons of chronic cor pulmonale. A further very common
      reason is obstructive sleep apnea syndrome (OSAS), especially, if combined with a
      COPD. In this case prevalence of cor pulmonale rises up to 80%. The development
      of a chronic cor pulmonale is the most striking negative prognostic factor for
      these patients. Just 30% of COPD patients with cor pulmonale survive longer than
      5 years. Only the early detection of respiratory disturbances, which potentially
      might lead to cor pulmonale, and their consequent therapy are able to improve the
      patients' prognosis.

PMID- 16802519
TI  - [Therapy of heart failure in the elderly].
AB  - Chronic heart failure is one of the most common diseases in internal medicine.
      Systolic and diastolic heart failure can be distinguished. According to the
      guidelines therapy consists of beta-blockers, ACE inhibitors/AT1 receptor
      antagonists, diuretics, aldosterone antagonists, and glycosides. Older patients
      should also be treated following the guidelines. However, side effects and
      interactions between drugs are more frequent and require special attention. The
      majority of concomitant diseases are no contraindication to heart failure
      treatment.

PMID- 16802520
TI  - [Coronary artery disease: what's different in women?].
AB  - Cardiovascular disease remains the leading cause of mortality for women and men
      in developed countries. Although coronary artery disease is the major cause of
      morbidity and mortality in women, coronary heart disease in women is still
      clinically underestimated. Although the incidence of coronary heart disease
      increases with age in women, the clinical presentation of the disease lags 10
      years behind that in men. Unfortunately, the routinely available noninvasive
      tests used to screen the presence of coronary artery disease have been relatively
      insensitive and nonspecific for women. However, recent advances in device
      application, adjunctive therapies and surgical techniques suggest that coronary
      revascularization strategies are safe and effective for women and men.

PMID- 16802521
TI  - [Chronic inflammatory bowel disease and cardiovascular complications].
AB  - The most common extraintestinal manifestations of Crohn's disease and ulcerative
      colitis are iritis and uveitis, primary sclerosing cholangitis (PSC) and nodal
      erythema and pyoderma gangrenosum. Complications within the cardiovascular system
      seem to be uncommon, but there are no systematic investigations concerning the
      epidemiology of these manifestations. There are more than 100 cases reported
      about pericarditis and perimyocarditis in patients with inflammatory bowel
      disease. Other patients with Crohn's disease or ulcerative colitis suffer from
      vasculitis, representing a further mechanism of inflammatory diseases of the
      cardiovascular system. There are several case reports showing a combination of
      Takayasu's arteritis and Crohn's disease, and cross-reacting antibodies against
      gut mucosa and aortic tissue were found. Some patients developed thrombotic
      complications by activating the coagulation system, which can result in atrial
      thrombi, embolism of the pulmonary arteries, myocardial infarction and
      disseminated intravascular coagulopathy (DIC). Furthermore, a few case were
      reported about atrio ventricular blocks, amyloidosis of the heart, dilative
      cardiomyopathy and endomyocardial fibrosis in patients with chronic inflammatory
      bowel disease. Here, a 27-year-old patient with known ulcerative colitis for 2
      years is reported, who presented in the authors' department with unstable angina
      pectoris. Coronary angiographic examination was immediately performed and diffuse
      intracoronary thrombi were found, which could be removed by the catheter
      procedure. A myocardial infarction did not develop. Because of positive anti
      neutrophil cytoplasmic antibodies (p-ANCA) a p-ANCA-positive arteritis of the
      coronary vessels with intracoronary thromboembolism due to ulcerative colitis was
      diagnosed. Systematic studies or investigations concerning the epidemiology of
      the cardiovascular complications are still lacking, so that an overview about the
      published data is given.

PMID- 16802522
TI  - [Physical activity, hypertension, and cardiac and circulatory system].
AB  - Because of its increasing incidence hypertension is--as one of the most important
      risk factor of diseases of the cardiac and circulatory system--a challenge for
      prevention and rehabilitation. Besides the established pharmacological therapy
      regular physical activity is one of the effective nonpharmacological therapies;
      particularly, there are also effects on other risk factors. Meta-analyses show a
      decreasing effect of physical activity both on the systolic and diastolic value.
      With a nonresponder rate of 25% the effects are similar to pharmacological
      therapy. Modulators can be found in the pathology of the disease itself, in the
      age, and in genetic polymorphisms. The mechanisms for blood pressure reduction
      might be the diuretic effect of physical activity, the reorganization of the
      vegetative reaction toward a sympathicolysis, the humeral modifications like
      changes in glucose metabolism and the improvement of endothelial function.
      Recommendations concerning the nature, the intensity and duration of physical
      activity refer more to consent statements than to evidence-based studies.
      Nevertheless, the following recommendations can be given. Endurance events with
      cyclic movements should be performed at a moderate intensity between 40% and 60%
      VO2(max). Though a duration of 60-90 min has the highest effect on blood pressure
      reduction, a duration of only 30 min per unit is favored to reach a higher
      compliance. No influence has yet been verified concerning the frequency of
      physical activity. Because of its effects on risk factors other than hypertension
      physical activity represents an all-embracing treatment concept. Therefore it is
      desirable to integrate physical activity in the treatment routine, especially in
      the therapy of patients with different risk factors.

PMID- 16802523
TI  - [Mind and heart--heart and mind].
AB  - In common parlance, the close relationship between the heart and the mind is well
      known. Epidemiologic investigations of the last 20 years have put this
      relationship on an empirically confirmed basis: patients with heart disease,
      especially coronary artery disease, suffer from major depression at a rate
      exceeding chance alone. The reasons are still unknown, but current hypotheses
      focus on the influence of depression on endothelial function, blood coagulation,
      cardiac arrhythmias, inflammatory reactions, and lifestyle factors. Major
      depression worsens the prognosis of cardiologic disorders. Depression in patients
      with heart disease must be treated equally vigorously as in patients without
      heart disease. In patients with coronary artery disease and depression, only few
      controlled clinical studies are available, but have shown that selective
      serotonin reuptake inhibitors are effective and safe. They are therefore
      currently the drugs of choice. It is important for the clinician to consider
      major and minor depression in the differential diagnosis of psychiatric and
      somatic symptoms in patients with heart disease, to diagnose depression without
      delay, and promptly initiate an appropriate therapy according to current
      treatment guidelines.

PMID- 16802524
TI  - [Cardiac alterations caused by renal failure].
AB  - Cardiac disease is the most common cause of death in patients with endstage renal
      disease. It was assumed that the high rate of cardiovascular mortality was based
      on accelerated atherosclerosis. Recently published articles, however,
      demonstrated that only 30-50% of all cardiac deaths in patients with uremia was
      due to myocardial infarction. On the other hand 30-40% of all patients with renal
      insufficiency, angina pectoris and documented ischemia have normal coronary
      arteries. Therefore, it is suggested that in patients with chronic uremia apart
      from accelerated atherosclerosis further abnormalities of the heart lead to
      myocardial ischemia. Recently published papers report functional and structural
      changes, which affect myocardial perfusion reserve. These structural changes
      include left ventricular hypertrophy, interstitial myocardial fibrosis, and
      microvascular disease.

PMID- 16802525
TI  - [Sleep apnea syndrome--hypertension--cardiac failure].
AB  - Especially middle-aged persons frequently suffer from sleep-related breathing
      disorders. In particular, in sleep apnea syndrome various interactions are known
      concerning the development or deterioration of hypertension. Cardiac failure may
      as well be a consequence of a sleep apnea syndrome. It may negatively influence
      sleep apnea. The causes of cardiovascular secondary and concomitant diseases are
      blood gas alterations, intrathoracic fluctuations in pressure and consecutive
      arousal reactions, which again cause various secondary and concomitant disorders.
      The various and partly incompletely discovered relationships between sleep apnea
      syndrome on the one hand and hypertension and cardiac failure on the other hand
      offer the possibility of causal treatment for these disorders.

PMID- 16802526
TI  - [Autonomic dysfunction and orthostatic intolerance. Cardiologic diagnosis and
      treatment options].
AB  - Various disorders of autonomic circulatory control are characterized by symptoms
      of orthostatic intolerance and syncope. Since the introduction of tilt-table
      testing as a cardiac diagnostic tool by Kenny et al., definition of these
      disorders has changed significantly. This review summarizes the current knowledge
      of diagnosis and treatment of the syndromes of orthostatic intolerance.

PMID- 16802527
TI  - [Future perspectives of cardiovascular intensive care medicine].
AB  - The future perspectives of cardiovascular intensive care medicine (CVICM) are
      affected by an ever increasing number of elderly (> 65 years), old (> 75 years)
      and very old (> 85 years) patients with the incidental clinical consequences, by
      an increase in inpatient days due to the increasing number of patients who have
      to be treated despite cost pressure, and by the attempts to integrate CVICM into
      one interdisciplinary intensive care unit (ICU) including medical and surgical
      patients, although proof of equal or even superior outcome, process or structural
      quality is lacking presently. To overcome all the problems mentioned, CVICM must
      develop from a mainly consensus-oriented to a more evidence-oriented medicine;
      CVICM must find ways to improve the poorly validated hemodynamic monitoring
      concept by pulmonary artery catheter and look for additional, less invasive
      monitoring techniques and better monitoring parameters; CVICM must support the
      search for new and hopefully better pharmacotherapeutic agents and cardiovascular
      assist devices as presently available to support the failing heart and the
      impaired vascular system; and CVICM must also learn to control noncardiac
      processes like inflammation and multi-organ failure, which often are responsible
      for the fatal outcome of the ICU patient with cardiovascular disease. Real
      challenges for the cardiovascular intensivist are refractory shock and refractory
      septic cardiomyopathy, these cardiovascular disease entities being responsible
      for every other fatality in the wake of severe sepsis and septic shock. To handle
      these tremendous challenges of CVICM, training of the young cardiologists in
      CVICM must be intensified, and much more attention to cardiovascular topics and
      techniques must be paid when training our colleagues in medical intensive care
      medicine.

PMID- 16802528
TI  - [Methods and pharmacology in cardiopulmonary resuscitation. What's new?].
AB  - BACKGROUND: Initiation of effective cardiopulmonary resuscitation (CPR) at the
      earliest possible time is the most important determinant of prognosis for
      patients with prehospital cardiac arrest. Basic life support CPR, defibrillation
      by emergency medical systems or first responders as well as vasopressor drugs or
      antiarrhythmics are essential. RESULTS: Today, cardiocompression seems to be
      superior to ventilation. Defibrillation is the most effective treatment for
      ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT). The
      effectiveness of defibrillation diminishes rapidly over time. The use of
      automated external defibrillators (AED) by first responders is very promising
      with excellent results caused by a short "call-to-arrival" time. Epinephrine and
      vasopressin are pressor drugs used in the treatment of cardiac arrest with
      similar success rates. Among antiarrhythmic drugs, lidocaine should no longer be
      used in patients with cardiac arrest, whereas amiodarone has high efficacy rates
      in VF or pulseless VT. CONCLUSION: Technique and methods of resuscitation are
      ranging from CPR to additional drugs. Fast and consequent work is essential.
      Among the "chain of survival" there is an increased value of first responders.

PMID- 16802529
TI  - [Management of acute renal failure in intensive care patients].
AB  - Crucial for the management of acute renal failure is the differentiation in a
      prerenal, renal and postrenal form. Prerenal acute renal failure, i.e.,
      hypovolemia, and postrenal acute renal failure, i.e., urinary obstruction, can be
      treated specifically, and generally, these forms of acute renal failure resolve
      quickly. By contrast, for intrinsic acute renal failure with acute tubular
      necrosis, there is no specific therapy and supportive care is necessary until
      renal function resumes. Prevention of intrinsic acute renal failure is important,
      i.e., avoidance of nephrotoxic substances, maintenance of adequate hydration and
      perfusion, cure of septic foci. However, in intensive care patients the
      development of acute renal failure often cannot be prevented. With the incidence
      of acute renal failure, the prognosis of intensive care patients deteriorates
      significantly. Temporary extracorporeal detoxification is often necessary, until
      eventually, there is a restitution of renal function. The prognosis of acute
      renal failure in intensive care patients is poor, if there is preexisting renal
      disease or the cause of the acute renal failure cannot be eliminated.

PMID- 16802530
TI  - [Diagnosis and therapy of pulmonary embolism].
AB  - Pulmonary embolism (PE) as a potentially life-threatening condition requires
      immediate medical intervention. Even the mere suspicion of a PE demands the
      initiation of a therapy with heparin. According to the patient's hemodynamic
      stability further diagnostic and therapeutic steps have to be taken. In case of a
      stable hemodynamic situation both the clinical probability of a PE and diagnostic
      imaging as well as the determination of D-dimers lead to the diagnosis. These
      patients should be anticoagulated with heparin. Unstable hemodynamic patients
      need to be monitored on the intensive care unit; echocardiography and, if needed,
      spiral computed tomography are the most important diagnostic tools. Due to this
      serious situation lung artery perfusion needs to be restituted by thrombolysis.
      Additionally, secondary prevention with vitamin K antagonists (INR [International
      Normalized Ratio] 2.0-3.0) is recommended depending on anamnesis and accordance
      to a risk group.

PMID- 16802531
TI  - Diabetic ketoacidosis and hyperosmolar hyperglycemic state.
AB  - Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the
      two most serious metabolic complications of diabetes mellitus (DM). These
      disorders can occur in both type 1 and type 2 DM. DKA is characterized by
      hyperglycemia, ketone body formation and metabolic acidosis. Precipitating causes
      are usually infection or insulin omission. Over the past 20 years, there has been
      no reduction in the DKA mortality rates, which remain between 3.4% and 4.6%. HHS
      is manifested by marked elevation of blood glucose, hyperosmolality and little or
      no ketosis. Precipitating causes of HHS are infection, undiagnosed diabetes and
      substance abuse. The mortality rates of the HHS remain high at approximately 15%.
      Basic common pathophysiological mechanisms in both conditions, which differ only
      in the magnitude of dehydration and degree of ketoacidosis, are the reduction in
      the effective insulin action combined with increased counterregulatory hormones
      (glucagon, catecholamines, cortisol, and growth hormone). While in DKA the lack
      of insulin combined with increased catecholamines results in accelerated
      lipolysis and thus production of excess fatty acids, leading to beta-oxidation
      and ketogenesis, in HHS residual beta-cell function is adequate to prevent
      lipolysis but not hyperglycemia. The prognosis of both conditions is
      substantially worsened in patients > 65 years of age and in the presence of coma
      and hypotension. Mainstays of therapy are intravenous insulin and fluid
      replacement as well as the concomitant treatment of the precipitating factors.
      Improved patient education and implementation of measures such as home glucose
      and ketone monitoring might decrease the number of hospital admissions due to DKA
      and HHS, which are, in their majority, preventable).

PMID- 16802532
TI  - [Noninvasive ventilation in medical intensive care medicine].
AB  - Noninvasive ventilation refers to mechanical respiratory assist not requiring an
      endotracheal airway. Potential advantages include the reduction of complications
      resulting from intubation and invasive long-term mechanical ventilation and
      possibly a reduced time demand on medical personnel in the long run. Patients
      with additional severe organ failure, lacking ability to cooperate or high risk
      of aspiration are not suitable for noninvasive ventilation. Noninvasive
      ventilation has proven to be effective in reducing symptoms, need for intubation
      and mortality in selected patients with exacerbations of chronic obstructive lung
      disease. For pulmonary edema noninvasive CPAP (continuous positive airway
      pressure) reduces the symptoms and the need for intubation, although studies have
      not demonstrated a reduction in mortality. In other forms of acute respiratory
      failure noninvasive ventilation may be helpful, but its final role still has to
      be established. In these patients a trial of noninvasive ventilation appears to
      be safe as long as patients are carefully selected and intubation is not
      prolonged.

PMID- 16802533
TI  - [Specific therapy in acute liver failure].
AB  - Acute liver failure is defined as hepatic insufficiency (icterus and
      coagulopathy), hepatorenal syndrome and encephalopathy, associated with a high
      mortality. A number of conditions can cause this sudden severe liver failure,
      which finally triggers a multi-organ response. Its etiology shows considerable
      geographic variation, with viral hepatitis being the most common cause worldwide,
      whilst drugs, especially acetaminophen-induced hepatotoxicity, form the most
      common precipitant in many developed countries. The essential feature of a wide
      variety of agents is apoptosis and/or necrosis of liver cells which is associated
      with liver injury and insufficiency. Based on new experimental data, the
      identification of target molecules involved in apoptosis may offer new
      therapeutic options and improvement of prognosis scores in patients with acute
      liver failure.

PMID- 16802534
TI  - [Quality assurance and guidelines in intensive care medicine].
AB  - Although validated instruments are readily available for structured outcome
      assessment, this has been rarely employed in German intensive care units yet.
      Analysis of the effectiveness or efficiency of intensive care medicine without
      systematic assessment of outcomes and underlying structures and processes is
      impossible. Detailed knowledge of outcomes is mandatory, when continuous quality
      improvement is warranted. In the future, German intensive care units should
      implement regular outcome assessment to allow objective comparisons considering
      the particular case mix. Evidence-based guidelines may facilitate both,
      development of objectives, and assessment of outcomes. Owing to the advancement
      of medicine regular updates of guidelines are mandatory. Moreover, targets for
      the quality assessment need to be adjusted accordingly. This finally leads toward
      a continuous quality improvement process.

PMID- 16802535
TI  - [Therapy of acute decompensated heart failure with levosimendan].
AB  - PURPOSE: To determine the short-term hemodynamic and clinical effects of
      levosimendan, a calcium-sensitizing agent, in patients with decompensated heart
      failure. PATIENTS AND METHODS: Seven patients with cardiogenic shock requiring
      catecholamines (two patients with acute myocardial infarction, two patients with
      decompensated hypertensive heart disease, one patient with low cardiac output
      with ischemic cardiomyopathy, two patients with dilated cardiomyopathy [ethyl
      toxic, polymyositis] with a cardiac index < or = 2.5 ) 1 x min(-1) x m(-2) and a
      pulmonary wedge pressure > or = 15 mmHg received levosimendan with an initial
      loading dose of 12 microg/kg over 10 min followed by a continuous infusion of 0.1
      microg/kg/min for 24 h. RESULTS: During levosimendan infusion an increase in
      cardiac index (30% after 6 h and 24 h), a decrease in heart rate (4% after 6 h
      and 10% after 24 h, respectively), and a decrease in systemic vascular resistance
      (27% after 6 h and 41% after 24 h, respectively) appeared. In combination with
      volume resuscitation the pulmonary capillary wedge pressure increased. Under
      therapy with levosimendan no relevant adverse events occurred; there was no
      increase in severe cardiac arrhythmias and QT interval duration. CONCLUSION:
      Levosimendan causes rapid improvement in hemodynamic function in patients with
      cardiogenic shock. These hemodynamic effects are not associated with relevant
      adverse events. Levosimendan may be of value in the short-term management of
      patients with cardiogenic shock.

PMID- 16802536
TI  - [Myelodysplastic syndromes--new treatment options].
AB  - Myelodysplastic syndromes (MSD) are acquired disorders of the bone marrow,
      characterized by defects in maturation and function of hematopoietic stem cells,
      ineffective hemopoiesis and risk of evolution to acute leukemia. Using prognostic
      scoring systems like the IPSS (International Prognostic Scoring System) or the
      Dusseldorf Score allows to predict the course of the disease, separating low-risk
      patients from high-risk patients. In the past, transfusion of red cells was the
      only treatment in the vast majority of patients. Today, there are promising drugs
      available, either within treatment studies or in the near future approved by
      health authorities. Low-risk patients may respond to antithymocyte globulin,
      valproic acid and Revlimid in 5q-patients. Erythropoietin (EPO) +/- granulocyte
      colony-stimulating factor (G-CSF) should be administered in patients with a low
      EPO level. High-risk patients aged < 60 years can be cured by allogeneic stem
      cell transplantation. Older high-risk patients are likely to respond to
      epigenetic treatment with 5-azacytidine or decitabine, even in case of
      chromosomal anomalies. After exact diagnosis using FAB and/or WHO classification
      and evaluation of prognosis, patients should be treated according to their
      individual profile. In the near future, the aim is not only to improve quality of
      life but also to prolong life expectancy.

PMID- 16802537
TI  - [Update hepatitis D].
AB  - The relevance of chronic hepatitis delta results from its high morbidity.
      Prevalence of hepatitis D decreases in classic endemic areas of the Mediterranean
      Basin, but increases in Eastern European countries. Hepatitis D is mainly a
      disease of immigrants in Germany. Hepatitis D virus (HDV) is an incomplete virus,
      which needs the hepatitis B surface protein (HBsAg) but not hepatitis B virus
      (HBV) replication for its propagation. In case of HBsAg detection a screening for
      HDV antibodies should be performed. Simultaneous HDV/HBV infection leading to
      spontaneous virus clearance in the majority of cases has to be differentiated
      from HDV superinfection with a high rate of chronification. Chronic hepatitis D
      is difficult to treat. Treatment regimens for hepatitis D are interferon-based so
      far. Pegylated interferons, a prolongation of treatment beyond 12 months,
      combination therapies with ribavirin and prenylation inhibitors are possibly new
      therapeutic options in chronic hepatitis C.

PMID- 16802538
TI  - HFE mutations in idiopathic dilated cardiomyopathy.
AB  - BACKGROUND AND PURPOSE: Dilated cardiomyopathy is a typical complication of
      hereditary hemochromatosis (HH). The present study investigated, whether
      mutations of the hemochromatosis (HFE) gene might be etiologic and disease
      modifying factors in idiopathic dilated cardiomyopathy PATIENTS AND METHODS:
      Clinical and biochemical assessment and HFE gene analysis were perfomed in 46
      patients with IDCM and 350 healthy controls. Cardiomyopathy was angiographically
      defined according to the criteria of the Collaborative Research Group of the
      European Human and Capital Mobility Project of Familial Dilated Cardiomyopathy.
      RESULTS: A higher prevalence of C282Y homozygosity was found among patients with
      IDCM compared to healthy subjects (4.3% vs. 0.6%; p < 0.02). A total of 6.5% of
      the patients with IDCM were either C282Y homozygotes or C282Y/H63D compound
      heterozygotes. The C282Y allele frequency was somewhat higher among patients with
      IDCM (8.7%) compared to healthy controls (5.4%; p < 0.2), whereas the H63D allele
      frequency was not increased. No significant differences of serum iron, ferritin
      or transferrin saturation, cardiac iron loading, NYHA classification, Lown's
      classification, the history of cardiopulmonary resuscitation, LVEDD (left
      ventricular end-diastolic diameter), EF (ejection fraction), LADD (left atrial
      end-diastolic diameter) and CI (cardiac index) were seen between HFE carriers and
      noncarriers. CONCLUSION: The present study indicates that it is worth screening
      patients with IDCM for iron parameters given the increased prevalence of disease
      predisposing HFE constellations. It remains unclear, to what extent iron or
      immune-mediated processes contribute to the pathomechanism of IDCM.

PMID- 16802539
TI  - [Functional and inflammatory bowel disorders].
AB  - BACKGROUND: Current investigations suggest that postinflammatory mechanisms might
      induce subtle changes in the mucosa and enteric nervous system which cannot be
      readily detected by routine diagnostic measures in subgroups of functional bowel
      disorders, especially in postinfectious irritable bowel syndrome (PI-IBS).
      DEFINITION OF PI-IBS: Characteristic of IBS is a symptom cluster with abdominal
      pain/discomfort and altered bowel movement without pathologic findings during
      routine work-up. PI-IBS is characterized by acute onset of symptoms, fever,
      vomiting, diarrhea and/or positive stool culture. EPIDEMIOLOGY: The incidence of
      PI-IBS is 10-17% in unselected IBS patients of whom 70% develop diarrhea, 26%
      alternating bowel movement and 8% constipation. PATHOPHYSIOLOGY: Initial
      gastrointestinal infections might induce subtle ongoing inflammation with
      consecutive altered mucosal function. Pathomechanisms include mutations within
      the interleukin-(IL-) 10 promoter polymorphism, hyperplasia of specialized cells
      including Paneth and enteroendocrine cells (EC) through cytokines as well as
      inflammatory-mediated modulation of neurones and neurotransmitters within the
      enteric nervous system. DIAGNOSIS, DIFFERENTIAL DIAGNOSIS, AND THERAPY: It is
      essential to exclude alarm symptoms. IBS can be positively diagnosed with a
      sensitivity and specificity of > 90% by standardized questionnaires. Indications
      of PI-IBS are the acute onset of symptoms, fever, vomiting, diarrhea and/or
      positive stool culture. Differential diagnoses include lactose intolerance, small
      bowel bacterial overgrowth, bile acid malabsorption, celiac disease, giardiasis,
      chronic inflammatory bowel disease, collagenous colitis, and diverticulitis.
      Therapeutic options in PI-IBS remain symptomatic. So far, no specific anti
      inflammatory treatment modalities are available.

PMID- 16802540
TI  - [New strategies in diagnosis and therapy of vasculitides].
AB  - Vasculitides are a heterogeneous group of diseases, with an incidence of 38-54
      cases per 1 million people. These diseases are characterized by an inflammatory
      infiltration of the vessel wall. The clinical diagnosis is difficult to establish
      because of the lack of diagnostic criteria, despite the fact, that such criteria
      are increasingly being developed. The established therapy of primary vasculitic
      syndromes is still the combination of cyclophosphamide and corticosteroids. This
      drug combination is highly effective but correlated with a wide range of side
      effects. During recent years two research paths have been followed: (1) to find a
      medication, which is as effective as cyclophosphamide, but potentially less
      toxic; (2) to investigate the use of rituximab in case of a poor response to the
      classic treatment or in case of unacceptable side effects.

PMID- 16802541
TI  - [Atrial fibrillation: current therapeutic options].
AB  - The treatment of atrial fibrillation still remains challenging in everyday
      practice. Even after the introduction of catheter ablation, the decision making
      about the type of therapy became more complex. The recently published guidelines
      of the American Heart Association, the American College of Cardiology, and the
      European Society of Cardiology clearly show therapeutic approaches for different
      types of atrial fibrillation. The fear of thromboembolism still forces the
      physician to restore sinus rhythms and perform a perfect anticoagulation. Based
      on large studies, we are able to decide for each patient individually whether
      oral anticoagulation or acetylsalicylic acid/clopidogrel are required. Future
      studies in a large cohort of patients are still necessary to clarify the value of
      interventional therapy in conjunction with antiarrhythmic drug therapy. These
      will provide patients with a safe therapy and high quality of life despite
      presenting paroxysmal or persistent atrial fibrillation.

PMID- 16802542
TI  - [Possibilities of reducing heart rate by I(f)-channel inhibitors].
AB  - The heart rate represents a marker of cardiac workload and oxygen demand. It is
      an expression of increased sympathetic tone und thus an important prognostic
      parameter. The heart rate is modulated at the sinus node by the slew rate of the
      slow diastolic depolarization. This is determined by the activation of the I(f)
      channel. A new approach is the specific inhibition of this channel by ivabradine.
      Clinically, this drug leads to a decrease of heart rate and ischemic phases, more
      pronounced as by atenolol. For the future ivabradine represents a new possibility
      for the therapy of coronary heart disease, maybe also of heart failure or
      specific arrhythmias involving the sinus node.

PMID- 16802543
TI  - [Diagnosis, treatment, and prognosis of renal artery stenosis].
AB  - With the increasing age of the population we must be prepared for a higher number
      of patients with renal artery occlusive disease. The clinical importance of renal
      artery stenosis is the induction of severe hypertension and renal dysfunction or
      even dialysis dependency. In this context it is of importance to realize that the
      presence of renal artery stenosis is not always responsible for hypertension and
      renal dysfunction in the individual patient and that only a stenosis > 60-70%
      diameter reduction can be considered hemodynamically significant. Typical
      clinical symptoms are helpful to select patients for further screening methods.
      In this setting a prominent role of color duplex sonography is seen.
      Nevertheless, intraarterial angiography remains the gold standard. All treatment
      options (surgery, angioplasty and medical treatment alone) have specific
      advantages and disadvantages which should be considered in the individual case
      and must be reconsidered during follow-up. Independent of the treatment chosen,
      control of all cardiovascular risk factors needs consideration. The selection for
      invasive treatment requires a careful assessment of the hemodynamic significance
      of the stenosis, the presence of irreversible parenchymatous damage and the
      clarification of the treatment goals in the patient. The practical challenge for
      the clinician is to carefully consider the benefit and the risks associated with
      the various types of treatment and to select the best treatment for the
      individual patient.

PMID- 16802544
TI  - [Early diagnosis of chronic kidney disease. New insights into creatinine and
      proteinuria].
AB  - The progression of chronic kidney disease (CKD) is more than just a simple,
      creeping loss of kidney function finally resulting in end-stage renal disease
      (ESRD). First, the growing incidence of CKD implies an exploding socioeconomic
      burden. Second, clear evidence indicates that CKD is associated with an
      independent massive increase in the patient's cardiovascular risk. Concerning
      screening and early diagnosis of CKD serum creatinine alone is an inadequate
      parameter for the evaluation of renal function. Proteinuria is both an indicator
      of renal damage as well as a progression factor for ongoing loss of renal
      function. Optimized treatment of arterial hypertension is of outstanding
      importance in the management of CKD patients, since high blood pressure is
      directly as well indirectly, via proteinuria, related to progression of CKD.
      Agents interfering with the renin-angiotensin system have been proven to be
      especially effective in antiproteinuric treatment and in slowing the progression
      of CKD. Our current understanding of optimized antihypertensive and
      antiproteinuric therapy favors a multimodal treatment regimen. Reduction of
      proteinuria toward levels < 0.5 g per day would be ideal. By this intervention
      the risk for both ongoing renal function loss as well as the risk of
      cardiovascular disease can be markedly reduced.

PMID- 16802545
TI  - [Vitamins and trace elements in nutrition. Update 2005].
AB  - In Germany sales of vitamin and trace element supplements are 1,2 billion Euros
      per year. In the light of this dimension and the increasing tendency toward food
      fortification, medicine and nutritional science have to state their point of
      view, where supplementation is useful, where it might be useful, and where it is
      useless or possibly dangerous. Supposing a balanced diet, nutritional
      requirements are covered in adults. Only in the area of calcium, folic acid,
      iodine, and vitamin D a gap in supplies can be discovered in average nutrition.
      Those requirements should be covered with a balanced diet. The intention of
      supplementation in this field is the potential health benefit of a requirement
      exceeding supplementation. Especially antioxidants are sometimes suggested to
      have such effects. From a scientific view a general recommendation, especially
      for multivitamin supplementation, cannot be given. In contrast to young adults,
      elderly persons frequently suffer from single or general micronutrient
      deficiencies. The intention of supplementation in this field is the coverage of
      nutritional requirements and the therapy of specific nutritional deficiencies,
      which should be compensated, even though scientific evidence in some fields is
      weak.

PMID- 16802546
TI  - [Headaches in nonneurologic diseases].
AB  - Headaches can be classified into primary and secondary headaches. Typical
      examples of primary headaches are migraine, tension-type headache and cluster
      headache. Secondary headaches in internal medicine might be due to hypertensive
      encephalopathy, lung diseases, metabolic and endocrine diseases and disturbances
      of electrolytes like increased and decreased serum calcium levels. Ibuprofen,
      immunoglobulins, and antibiotics might lead to aseptic meningitis. Drug-induced
      headaches are seen after use of nitroglycerine, calcium channel blockers and
      immunoglobulins.

PMID- 16802547
TI  - [Diagnosis and therapy of endocrine hypertension].
AB  - Once the diagnosis of hypertension is established, secondary forms should be
      considered. Especially hormonally active adrenal tumors may allow specific
      treatment. For primary hyperaldosteronism plasma aldosterone to active renin
      concentration ratio in patients with plasma aldosterone levels > or = 200 ng/l is
      a reliable screening method under random conditions. A salt loading test may
      confirm a primary aldosteronism. A unilateral adrenal adenoma has to be separated
      from bilateral adrenal hyperplasia. To exclude Cushing's syndrome, the
      dexamethasone challenge is a reliable screening parameter. Patients with
      Cushing's syndrome may have an elevated urinary free cortisol and the circadian
      rhythm may be abolished resulting in an elevated 23:00 h serum cortisol.
      Alternatively, cortisol may be measured in saliva using specific cutoffs.
      Determinations of 24-h urinary epinephrine and norepinephrine levels are
      established diagnostic tools for the diagnosis of pheochromocytoma.
      Metanephrines, which are metabolites of catecholamines, have been suggested as an
      alternative more sensitive and specific diagnostic tool. In conclusion, recently
      established biochemical methods are reliable screening parameters for the
      diagnosis of adrenal hypertension. Endocrine hypertension due to adrenal tumors
      may be treated by minimally invasive surgery or specific antihypertensive
      treatment.

PMID- 16802548
TI  - [Pharmacotherapy of osteoporosis: evidence-based clinical practice].
AB  - Since the foundation of the DVO ("Dachverband Osteologie") in 1999, it has been
      the continuous ambition to implement evidence-based medicine in the clinical
      course for the effective diagnosis and treatment of osteoporosis. This aim was
      addressed by the implementation of general guidelines (DVO) in 2003. These
      guidelines (DVO) offer strategies for diagnosis and treatment of osteoporosis in
      postmenopausal women, osteoporosis in elderly women and glucocorticoid-induced
      osteoporosis. Evidence-based treatment of osteoporosis recommends the
      supplementation with calcium and vitamin D, considering antiresorptive therapy
      antifracture efficacy is proven for the bisphosphonates alendronate, ibandronate
      and risedronate on the one hand and the SERM raloxifen on the other hand. On the
      basis of valid data from randomized, placebo-controlled clinical trials, new
      therapy regimen like rhPTH1-34 (teriparatide) or strontium ranelate fulfill the
      recommendation criteria for the guidelines (DVO). Effective treatment of
      glucocorticoid-induced osteoporosis includes supplemental calcium and vitamin D
      and antiresorptive agents like the bisphosphonates alendronate, risedronate and
      etidronate according to the guidelines (DVO).

PMID- 16802549
TI  - [Chemoreflexsensitivity is reduced in obstructive sleep apnea and might be
      modulated by the autonomic system].
AB  - BACKGROUND: Chemoreflexes are important mechanisms for regulating ventilatory and
      cardiovascular function, which are supposed to be influenced in obstructive sleep
      apnea (OSA). PATIENTS AND METHODS: For determination of chemoreflexsensitivity
      (CHRS) the ratio of the RR-interval shift in the surface ECG during 5 min
      inhalation of oxygen via a nose mask was formed in 15 patients with suspected
      OSA. Noradrenaline plasma concentrations were measured and were correlated to
      CHRS. RESULTS: Patients with OSA showed a reduced CHRS. CHRS was correlated to
      the severity of sleep apnea (respiratory disturbance index [RDI]; r = -0.622; p =
      0.013), and to minimal nocturnal oxygen saturation (r = 0.594; p = 0.032).
      Reduced CHRS was associated with higher noradrenaline concentrations (r = -0.542;
      p = 0.037). CONCLUSION: CHRS is reduced in patients with OSA and correlates with
      the severity of OSA. Further on, CHRS might be modulated by the autonomic system.
      Therefore, the determination of CHRS enables to estimate sympathetic activation
      in these patients.

PMID- 16802550
TI  - [Differentiation potential of stem cells from bone marrow].
AB  - Hematopoietic organs such as bone marrow contain various stem and progenitor
      cells with a differentiation capability exceeding hematopoiesis, a process also
      referred to as plasticity. Stem cells in bone marrow are hematopoietic stem
      cells, mesenchymal stem cells, and multipotent progenitor cells. Several examples
      for the development of stem cells of hematopoietic organs into nonhematopoietic
      tissue open novel ways in regenerative medicine. Animal experiments showed
      generation of neuronal tissue, cardiomyocytes and functional hepatocytes in
      injured tissue from bone marrow stem cells. Interpreting these results one has to
      keep in mind that besides transdifferentiation also cell fusion or heterogeneous
      stem cell populations might contribute to tissue regeneration. First clinical
      studies on therapy with bone marrow stem cells in myocardial infarction or liver
      embolization showed promising results.

PMID- 16802551
TI  - [The therapeutic effect of autologous bone marrow cells in ischemic heart
      disease].
AB  - Adult human bone marrow and peripheral blood contain diverse stem and progenitor
      cells with some properties resembling those of embryonic stem cells, as this has
      been revealed by an increasing body of evidence within the near past. Numerous in
      vitro experiments and subsequent animal studies have already demonstrated that
      these adult progenitor cells considerably contribute to the regeneration of
      ischemic or injured tissue. Over the last 4 years, several clinical studies
      employing such a hypothesis in the context of myocardial repair after acute
      infarction or during chronic ischemic heart disease have been published. These
      studies have used autologous bone marrow- as well as peripheral blood-derived
      progenitor cells, which were delivered via intracoronary or intramyocardial
      routes near the ischemic area. The initial results demonstrated the safety and
      possible benefit of this strategy, which appears to be relatively inexpensive and
      free of side effects. However, the present clinical studies were small in size so
      that the overall therapeutic efficacy remains open to debate and evaluation.
      Furthermore, a major part of the underlying repair mechanisms has been proposed
      but not yet elaborated. Hence, larger case-controlled, randomized and double
      blinded trials in addition to experimental investigations on the primary
      molecular mechanisms of myocardial repair are crucial for the future.

PMID- 16802552
TI  - [Mobilization of stem cells in cardiovascular disease. Improvement of
      vascularization, cardiac function and arrhythmias].
AB  - Besides re-injecting mostly autologous stem cells also the mobilization of stem
      cells from the bone marrow is increasingly evaluated. Mobilization of bone marrow
      cells can be induced by drugs, e.g., growth factors, or by physical exercise.
      Exercise leads to a number of physiological cardiopulmonary changes, and an
      improved vascularization of the heart and skeletal muscle, initiated by
      endothelial progenitor cells derived from the bone marrow. Particularly, duration
      exercise activates not only the release of CD34-positive cells, it also leads to
      increased pro- and anti-inflammatory cytokines, granulocyte colony-stimulating
      factor (G-CSF) being one of them. Originally, it was believed that therapeutic
      effects following bone marrow mobilization were based on the homing and
      transdifferentiation of bone marrow cells into cardiomyocytes, new data support
      the notion that the most important mechanism might be via paracrine and/or direct
      effects of G-CSF.

PMID- 16802553
TI  - [Myocardial infarct trial of Dusseldorf. Short- and long-term results after
      intracoronary stem cell transplantation in acute and chronic myocardial
      infarction].
AB  - Adult autologous bone marrow-derived cells contribute to the healing of
      myocardial infarction. At the author's institution patients after acute
      myocardial infarction and patients with chronic coronary heart disease and old
      infarction were treated. In both patient groups a significant decrease of the
      infarct area, an improvement of regional contractility and global left
      ventricular function could be demonstrated. Additional tests with SPECT and
      positron emission tomography could show an improved myocardial perfusion and an
      increased glucose uptake in the infarcted area after intracoronary bone marrow
      cell transplantation. Long-term controls of both patient groups could
      demonstrate, that the left ventricular pump function was not only increased after
      3 months, but also after 12 and 24 (-36) months, respectively. These results
      demonstrate that functional and metabolic regeneration of infarcted and
      chronically avital tissue can be released in humans by bone marrow-derived cell
      transplantation.

PMID- 16802554
TI  - [Transplantation of autologous adult bone marrow stem cells in patients with
      severe peripheral arterial occlusion disease].
AB  - BACKGROUND: For many patients with severe peripheral arterial occlusion disease
      (PAOD) an interventional or surgical treatment is not feasible. The regenerative
      potential of adult autologous mononuclear stem cells could contribute to
      neoangiogenesis. PATIENTS AND METHODS: Ten patients with severe PAOD were
      included. The walking distance was < 200 m and no interventional or surgical
      treatment was possible. After harvesting of 80 ml of bone marrow the mononuclear
      cell fraction was separated. Thereafter, intraarterial (10 ml into the common
      femoral artery) and intramuscular (5 ml into the muscles of the thigh and the
      lower leg) transplantation of the cell suspension was performed. RESULTS: After 2
      months the walking distance was enhanced significantly in all patients.
      Furthermore, a significant improvement of ankle-brachial index at rest, capillary
      venous oxygen saturation and parameters of venous occlusion plethysmography was
      seen. No complications or side effects could be monitored. CONCLUSION: These
      results demonstrate, that the combined intraarterial and intramuscular
      transplantation of autologous adult bone marrow stem cells leads to a significant
      improvement of perfusion indices in patients with severe PAOD.

PMID- 16802555
TI  - [Effects of exercise training on mobilization of BM-CPCs and migratory capacity
      as well as LVEF after AMI].
AB  - BACKGROUND AND PURPOSE: Bone marrow-derived circulating progenitor cells (BM
      CPCs) are mobilized in adult peripheral blood (PB) during the acute myocardial
      infarction (AMI) period and contribute to the regeneration of infarcted
      myocardium. In this study, the influence of physical training on the mobilization
      and the migratory activity of the BM-CPCs as well as on the left ventricular
      function (LVEF) after AMI was examined. PATIENTS AND METHODS: 26 patients with
      AMI were analyzed in two groups. The first group comprised 17 patients with
      standardized exercise training for 3 weeks 14 +/- 4 days after AMI, the second
      group nine control subjects without exercise training. PB concentrations of
      CD34/45+ and CD133/45+ were measured by FACS. The migratory activity of BM-CPCs
      was analyzed by migration assay. B-type natriuretic peptide (BNP) in PB and the
      functional investigations spiroergometry (VO2 and PaO2) and stress
      echocardiography (LVEF) were determined in both groups. RESULTS: A significant
      increase in both concentrations, CD34/45+ and CD133/45+, as well as in migratory
      capacity of BM-CPCs was found after 3 weeks of exercise training, which was
      significantly decreased 3 months after completion of exercise training. No
      significant difference was observed in the control group without exercise
      training. In the functional investigations a significant increase in VO2 as well
      as PaO2 was shown spiroergometrically after exercise training. There was no
      difference in stress echocardiographic LVEF at rest in both groups. On the other
      hand, interestingly, the findings showed that the increase of LVEF at peak stress
      was significantly higher after exercise training as compared to the control
      group. Moreover, a significant decrease in BNP values was found after exercise
      training as well as 3 months after AMI. No difference was found in the control
      group. CONCLUSION: This study demonstrates that exercise training for 3 weeks
      after AMI leads to a significant mobilization as well as increase of functional
      activation of BM-CPCs in humans. Moreover, regular exercise training might
      contribute to the positive effects on the regenerative potency after AMI.

PMID- 16802556
TI  - [Mesenchymal stem cells for cardiac regeneration].
AB  - Since physiological regeneration of cardiac muscle is limited, scar tissue
      replaces damaged myocardial tissue leading to impaired cardiac function. Whether
      stem cell therapy can prevent this process and regenerate cardiac tissue is the
      issue of many research projects at present. Some studies investigate mesenchymal
      stem cells (MSC) from bone marrow, which are known to have the potential to
      differentiate into various tissues. Under certain conditions the formation of
      cardiomyocytes was observed in vitro and in vivo, which, however, is a
      controversial issue. Nevertheless many investigators found an improvement of
      cardiac function after transplantation of MSC into damaged heart tissue. Since
      only few cells survive mid-term after transplantation, the impact of real cell
      replacement might be limited. Instead of or besides the replacement of lost cells
      by transdifferentiated MSC, the secretion of paracrine factors by MSC may be
      important for functional improvement. Thus, MSC show promising experimental
      results, and may be of therapeutic value for heart disease in the future.
      However, there are many unanswered questions and problems, which need to be
      resolved before.

PMID- 16802557
TI  - Wanted! Expert clinical advice on seating.

PMID- 16802558
TI  - A cost analysis of monoplace hyperbaric oxygen therapy with and without
      recirculation.
AB  - OBJECTIVE: Hyperbaric oxygen therapy is covered by the NHS under Specialist
      Services Definition Set 28. The indications and availability of the therapy have
      been influenced by educational failures, perceived costs and, compared with drug
      studies, the small number of controlled trials. This study aimed to inform this
      debate by calculating the direct costs to the health service of hyperbaric oxygen
      therapy for inpatients using a single, one-person chamber. METHOD: The costs
      included in this cost analysis were: hyperbaric chambers, staff, oxygen, property
      and cleaning, miscellaneous and general overheads. All costs are for 2004.
      RESULTS: Lower and upper costs were calculated. Start-up costs range from pounds
      64,800 to pounds 110,000 depending on the hardware selected. Annual costs,
      including 10-year amortisation of capital costs, range from pounds 40,069 to
      pounds 57,618 and per-treatment costs range from pounds 30 to pounds 41. Oxygen
      recirculation becomes cost effective after four to six years. CONCLUSION:
      Hyperbaric oxygen therapy is an inexpensive treatment that should be routinely
      available for conditions where evidence indicates that tissue hypoxia is a
      significant component of the injury or disease.

PMID- 16802559
TI  - The safety and efficacy of topical negative pressure in non-healing wounds: a
      systematic review.
AB  - Evidence on topical negative pressure from randomised controlled trials, non
      randomised comparative studies and case studies is considered. This is the first
      systematic review on this therapy to consider results by wound type.

PMID- 16802560
TI  - Do malnutrition and nutritional supplementation have an effect on the wound
      healing process?
AB  - Although nutrition is an extrinsic factor regulating wound healing, nutritional
      supplementation for the modulation of wound healing remains experimental.
      Evidence on the efficacy of supplementation in animals and humans is reviewed.

PMID- 16802561
TI  - Honey dressings: the need for specification.

PMID- 16802562
TI  - Accurate diagnosis and effective treatment of leg ulcers reduce prevalence, care
      time and costs.
AB  - OBJECTIVE: This long-term follow-up recorded the prevalence, aetiology and
      treatment of hard-to-heal leg and foot ulcers, and an estimated nurses' time
      spent providing care, for the years 1994-2005. METHOD: A questionnaire was sent
      to all district and community nurses in the county of Blekinge, Sweden, during
      one week in 1994, 1998, 2004 and 2005. Calculating the costs of hard-to-heal leg
      and foot ulcer care was not a primary aim, but the reduction in prevalence and
      time spent on wound management suggested it was important to illustrate the
      economic consequences of these changes over time. RESULTS: Estimated prevalence
      of hard-to-heal leg and foot ulcers reduced from 0.22% in 1994 to 0.15% in 2005.
      Treatment time decreased from 1.7 hours per patient per week in 1994 to 1.3 hours
      in 2005. Annual costs of leg and foot ulcer care reduced by SEK 6.96 million in
      the study area from 1994 to 2005. CONCLUSION: Improved wound management was
      demonstrated; leg and foot ulcer prevalence and treatment time were reduced. The
      results could be attributed to an increased interest in leg and foot ulcer care
      among staff, which was maintained by repeated questionnaires, continuous
      education, establishment of a wound healing centre in primary care and wound
      management recommendations from a multidisciplinary group. The improved ulcer
      care reduced considerably the annual costs of wound management in the area.

PMID- 16802563
TI  - Epidemiology, risk and prevention of pressure ulcers in critically ill patients:
      a literature review.
AB  - New nursing interventions and pressure-redistributing devices in intensive care
      units, and specific risk factors affecting critically ill patients, mean that
      different factors must be taken into consideration in preventing pressure ulcers.

PMID- 16802564
TI  - Unstable acute and chronic Charcot's deformity: staged skeletal and soft-tissue
      reconstruction.
AB  - Acute and chronic Charcot's foot deformity is a progressive, disabling and
      disfiguring condition that is prone to ulceration and infection. If conservative
      treatment is ineffective, bone and soft-tissue reconstruction is a viable option.

PMID- 16802565
TI  - [Women in natural sciences--Nobel Prize winners].
AB  - Alfred Bernhard Nobel was the founder of the Nobel Foundation, which has been
      awarding world-known scientists since 1901, for their contribution to the welfare
      of mankind. The life and accomplishments of Alfred Bernhard Nobel are described
      as well as scientific achivements of 11 women, Nobel prize winners in the field
      of physics, chemistry, physiology and/or medicine. They are Marie Sklodowska
      Curie, Maria Goeppert Mayer, Irene Joliot-Curie, Dorothy Crowfoot Hodgkin, Gerty
      Theresa Radnitz Cori, Rosalyn Sussman Yalow, Barbara McClintock, Rita Levi
      Montalcini, Gertrude Elion, Christine Nusslein-Volhard and Linda B. Buck.

PMID- 16802566
TI  - [Blood transfusion in patients with pertrochanteric femoral fracture].
AB  - AIM: The aim of the study was to investigate the pattern of transfusion in
      patients with pertrochanteric femoral fracture, and to compare the results
      obtained with literature data. METHODS: It was a retrospective study including
      246 consecutive patients operated on for pertrochanteric femoral fracture at
      University Hospital for Traumatology in Zagreb from January 1, 2001 to December
      31, 2003. The analysis included the method of operative treatment, type of
      anesthesia, physical status according to the American Society of Anesthesiology
      (ASA), preoperative hemoglobin levels, use of thromboprophylaxis, transfusion,
      and mortality. RESULTS: There were 246 patients with pertrochanteric femoral
      fracture; 244 (99.2%) underwent surgery and only 2 (0.8%) were treated
      conservatively. The method of treatment was DHS in 90.2%, and gamma nail in 8.9%
      of patients. Most patients were classified as ASA II, III and ASA IV (26.4%,
      54.9% and 18.7%, respectively), and most were operated on in spinal anesthesia.
      Thromboprophylaxis with low molecular weight heparins was administered to 98.4%
      of patients. The mean preoperative hemoglobin was 120 (88-152) g/L, and estimated
      blood loss during surgery was 300 (100-500) mL. Transfusion of packed
      erythrocytes was administered 135 (54.9%) patients, 62 (25.2%) during surgery.
      Fifteen (6.1%) patients received transfusion of blood plasma. DISCUSSION:
      Fractures in trochanteric region usually occur at age over 60 (80% of patients).
      Due to the patients' cardiovascular status the "transfusion trigger" remains
      undefined. Even relatively small alterations of the circulating volume make
      intraoperative blood pressure control rather challenging. CONCLUSION: The
      preoperative level of hemoglobin, clinical status of the patient, type of
      surgery, and anesthesia are useful predictors of transfusion therapy in patients
      with pertrochanteric hip fracture.

PMID- 16802567
TI  - [Infant mortality in Croatia 1993-2002].
AB  - In Croatia, infant mortality has been registered since 1874. During this period
      of time, a tremendous decline was recorded from 295.2/1000 live births in 1874 to
      7.0/1000 live births in 2002. A tenfold decline was recorded during the second
      half of the 20th century. In the last years, the decline has been slower.
      Significant differences were found among counties according to different years.
      AIM OF THE STUDY: The aim of the study was to analyze data on a ten-year period
      (1993-2002), to calculate total mortality rate for the country as a whole and for
      each county in separate, and to discuss the leading causes of infant death.
      METHODS: Mortality statistics data (death registers supplied by the Central
      Bureau of Statistics and Croatian National Institute of Public Health) were
      analyzed. The rate per 1000 and percentage were calculated for the four main
      death causes in each county. RESULTS AND DISCUSSION: The mortality rate for
      Croatia was 8.4 for the ten-year study period. Nine counties had rates above and
      11 counties below the rate for whole Croatia. The highest mortaliry rate was in
      Medimurje County (13.3) and lowest in Zagreb County (6.7). The leading causes of
      infant deaths in the whole country except for Medimurje County were perinatal
      causes (XVI according to ICD 10), followed by congenital malformations (XVII),
      symptoms (XVIII) and injuries (XlX). In four counties (Karlovacka, Bjelovarsko
      Bilogorska, Viroviticko-Podravska and Istarska), the third and fourth causes
      exchanged their places. The exception was Medimurje County where respiratory
      diseases ranked second (X), congenital malformations third and symptoms fourth.
      During ten years, 96 infants died because of injuries, calling for additional
      intervention to decrease the rate of these avoidable deaths in mainly healthy
      children. Data on ethnicity of dead infants were not available, so we could only
      presume that the difference in the Medimurje County was due to the greater
      proportion of Gypsies in the area. CONCLUSION: Further analysis is needed, taking
      into account the socioeconomic and ethnic data which are usually lacking in death
      certificates although anticipated to collect them. In conclusion, there is space
      for further decreasing infant mortality in Croatia. Analysis and intervention
      because of the great differences between counties are necessary, with special
      reference to Medimurje County because of its highest rate and quite a different
      pattern of infant deaths from other counties.

PMID- 16802568
TI  - [Characteristics of hyperhomocysteinemia in dialysis patients].
AB  - AIM: The aim of the study was to determine the prevalence of hyperhomocysteinemia
      and its relationship with other cardiovascular risk factors in dialysis patients.
      METHODS: Blood pressure and biochemical indicators (creatinine, urea, total
      cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) were determined
      by standard methods in 46 dialysis patients. Homocysteine (Hcy) was determined by
      the method of stable isotopic dilution mass spectrometry. ECHO of the heart was
      used for the parameters necessary for calculation of the left ventricular mass
      index. Left ventricular hypertrophy was defined as a left ventricular mass index
      higher than 109 +/- 20 g/m2 for males and higher than 89 +/- 15 g/m2 for females.
      Delivered dosage of dialysis (Kt/V) was calculated by Daugirdas formula. RESULTS:
      Arterial hypertension was present in 72% and left ventricular hypertrophy in 82%
      of study subjects. An increased concentration of total homocysteine (tHcy) (mean
      24.76 +/- 11.04 micromol/L) was observed in 85% of subjects. Dyslipemia was
      manifested by increased concentration of tChol in 22%, elevated values of LDL
      Chol in 26%, decreased concentration of HDL Chol in 50%, and hypertriglyceridemia
      in 46% of study subjects. There was no statistically significant correlation of
      plasma tHcy concentration with age (p > 0.5), creatinine (p > 0.2), time on
      dialysis (p > 0.9), dosage of dialysis (p > 0.78) and left ventricular mass index
      (p > 0.19). DISCUSSION: Numerous studies have shown that mild to moderate
      elevation of plasma tHcy concentration (tHcy 15-30 micrtomol/L, and 30-100
      micromol/L) occurs in 5%-7% of the general population and in 85%-90% of dialysis
      patients. In our study, hyperhomocysteinemia was present in 85% of patients.
      Increased tHcy concentration in plasma of uremic patients is one of non
      traditional atherosclerosis risk factors, acting synergestically with traditional
      risk factors for cardiovascular diseases in uremic patients. In patients on
      hemodialysis, dyslipidemia is generally characterized by increased concentrations
      of LDL cholesterol and triglycerides, and a decreased concentration of HDL
      cholesterol, as also confirmed by our study. In 43.5% of patients, inadequate
      dosage of dialysis is the consequence of insufficient function of the A-V fistula
      and lack of patient cooperation. Left ventricular hypertrophy is an independent
      risk factor for cardiovascular disease, while hypertension is one of its main
      causes. Literature data indicate that elevated arterial pressure and Hcy affect
      the degree of cardiac hypertrophy independently, and that Hcy is in direct
      correlation with heart failure for which decreased diastolic function is not
      responsible. Some 57%-93% of hemodialysis patients have left ventricular
      hypertrophy. In our study, left ventricular hypertrophy was observed in 81% of
      patients, of which 86% had arterial hypertension. CONCLUSION: The study has
      confirmed hyperhomocysteinemia in as many as 85% of patients. There was no
      positive correlation of Hcy concentration with patient age, time on dialysis,
      serum creatinine, adequacy of dialysis, left ventricular mass index.
      Cardiovascular diseases are common in dialyzed patients with
      hyperhomocysteinemia, suggesting a causal relationship since Hcy is an
      independent atherosclerosis risk factor. However, additional studies in a large
      number of subjects will hopefully provide more comprehensive answers.

PMID- 16802569
TI  - [Evaluation of examination stress based on the changes of sinus arrhythmia
      parameters].
AB  - AIM: The aim of this study was to assess changes during the pre-examination,
      examination and postexamination period investigation in the sinus arrhythmia
      parameters. EXAMINEES AND METHODS: Twelve female subjects, first year students of
      Psychology, matched by age and previous experience in taking exams, participated
      in the study. The state of anxiety, high activation and exam apprehension were
      assessed. The R-R cardiac intervals were continuously recorded by an eight
      channel polygraph (Powerlab). The measurements were made four times in the pre
      examination period (days-20, -10, -1 and immediately before the exam), and on two
      occasions after the exam (days 1 and 10 days of the exam). The recording of R-R
      intervals also began five minutes before the exam and continued during the exam
      and five minutes after the exam. RESULTS AND DISCUSSION: The level of anxiety,
      exam apprehension and high activation changed in a similar way, showing almost
      linear increase with the approaching of the exam. The changes of R-R interval
      parameters showed that stress was highest during the exam. The measurements and
      analysis of results showed a decrease of stress in the postexamination period.

PMID- 16802570
TI  - [Analysis of prognostic factors in breast cancer at University Hospital for
      Tumors].
AB  - Breast cancer is the most common malignant disease in women. It is rare before
      age 30, whereafter its prevalence rises to reach peak at age 50. Prognostic
      factors have a very important role in choosing the most appropriate treatment
      option and making long-term disease prognosis. Currently, the classic prognostic
      factors such as histologic type, tumor grade, tumor size, regional lymph node
      involvement, estrogen and progesterone receptor status still are of high
      prognostic value allowing for reliable prognosis. This retrospective study
      included female patients treated at Department of Surgery, University Hospital
      for Tumors in Zagreb over a two-year period (2002-2003). Only patients with
      histologically diagnosed invasive ductal breast cancer (NOS) undergoing radical
      modified mastectomy were included in the study. Analysis of the generally
      accepted prognostic parameters (tumor size, regional lymph node status, tumor
      grade, hormone receptor status) confirmed their known prognostic value. Study
      results were consistent with internationally reported data, reflecting
      appropriate approach by the surgery-pathology team of the hospital in the
      management of breast cancer.

PMID- 16802571
TI  - [Role of yeasts in diabetic foot ulcer infection].
AB  - AIMS: The aim was to assess the incidence of isolation of individual fungal
      species and interpret the meaning of fungal isolates from foot ulcers of 509
      diabetic outpatients using mycologic and histopathologic methods. Another aim was
      to explore risk factors for the development of fungal infections in foot ulcer.
      METHODS: Fungus isolation was made on selective media and their identification by
      standard mycologic methods. Histopathologic diagnosis of fungal ulcer infections
      was made on PAS-stained histopathologic preparations and imprint preparations
      (PAS and Papanicolaou staining) of foot wound biopsy specimens. RESULTS: Fungal
      and mixed foot ulcer infections were found in 14.9% of diabetic patients. In
      33.8% of patients, these infections were confirmed by a finding of fungal
      elements in histopathologic preparations of ulcer biopsy specimens, as follows:
      in 16.9% of patients, by finding fungal elements in imprint preparations of ulcer
      biopsy specimens and by isolation fungus from the swab of the same ulcer; in 2.3%
      by fungus isolation from ulcer biopsy specimens; in 36.9% by fungus isolation
      from ulcer swabs in pure culture and/or in a large number of colonies and/or from
      several ulcers on the foot of the same patient. More than 89% of patients had a
      single foot ulcer with fungal or mixed infection, big toe and the plantar
      metatarsal region in one foot or both feet being the most common sites of ulcer.
      Fifteen species from the genera Candida, Cryptococcus, Trichosporon and
      Rhodotorula were the causative agents of fungal and mixed foot ulcer infections.
      C. parapsilosis (in 61.5% of patients), and C. albicans and C. tropicalis (in
      10.8% of patients each) were the most common causes of these infections. The
      presence of yeasts and/or dermatophytes in the toe web of the same or other foot,
      or of both feet, did not influence the incidence of fungal and mixed foot ulcer
      infections. Patient sex and age, type and length of diabetes, or clinical picture
      of diabetic foot did not affect it either. In IDDM patients, the risk factor for
      the development of fungal and mixed foot ulcer infections was ulcer infection
      lasting for more than 13 weeks, whereas in NIDDM patients the length of ulcer
      infection did not contribute to the incidence of fungal and mixed foot ulcer
      infection. DISCUSSION: Our results and other reports suggest that Candida species
      are the most common fungal isolates (between 93.2% and 100% of all fungal
      isolates) from diabetic foot ulcer, with C. parapsilosis being the most common
      causative agent of fungal and mixed infection. From diabetic foot ulcer,
      bacterial isolation was 5 times as common as that of yeasts (327 vs. 65
      patients). Nevertheless, this investigation showed fungal isolates, originating
      not only from a primarily sterile ulcer sample (biopsy specimen) but also from
      foot ulcer swabs to be the causative agents (not ulcer colonizers or
      contaminants) of the foot ulcer infection. The pathogen c effect of yeasts in
      foot ulcer is indicated by the severity of clinical finding, chronic course of
      infection, and infection progression despite antibiotic therapy. Equally
      indicative are microbiologic diagnostic parameters (isolation in pure culture,
      and/or isolation in a large number of colonies, and/or isolation from several
      ulcers in the foot of the same patient). CONCLUSIONS: In diabetic patients at
      highest risk of developing fungal and mixed foot ulcer infections (IDDM patients
      with ulcer infection persisting for more than 13 weeks, and NIDDM patients with
      the clinical picture of deep ulcer and abscess in the plantar region,
      irrespective of the duration of ulcer infection), routine bacteriologic diagnosis
      should be supplemented with targeted mycologic and histopathologic methods.

PMID- 16802572
TI  - [Erectile dysfunction and cardiovascular disease].
AB  - Erectile dysfunction (ED) is a highly prevalent disorder worldwide. ED and
      cardiovascular disease (CVD) share many risk factors, the former often being the
      presenting symptom. The knowledge of the relationship between CVD and ED, the
      cardiovascular implications of phosphodiesterase type 5 inhibitors for the
      treatment of ED can help improve the quality of life of patients with both
      conditions. Cardiologists have a prominent role in treating ED.

PMID- 16802573
TI  - [Anderson-Fabry disease].
AB  - Anderson-Fabry disease is a rare inherited X-linked lysosomal storage disease
      caused by deficiency of the enzyme alpha-galactosidase A. The deficiency of alpha
      galactosidase activity leads to progressive, abnormal accumulation of neutral
      glycosphingolipids in the lysosome. With increasing age globotriaosylceramide
      (Gb3) progressively accumulates in different cells, tissues and organs throughout
      the body. The overall prevalence of Anderson-Fabry disease is 1:117.00 or 1:
      40.000 in (male) population. Typically, the clinical onset of Anderson-Fabry
      disease occurs during childhood or adolescence, with early symptoms of
      neuropathic pain (recurrent episodes of severe pain in the extremities),
      angiokeratomas (characteristic cutaneous lesions), oedematous upper eyelids,
      peripheral vasospasm and ophthalmological abnormalities. The disease progresses
      through adulthood and by the age of 30-40 years several major organ systems may
      be affected; cardiac disease, renal insufficiency, cerebrovascular attacks and
      neurologic findings are common. Death usually occur secondary to renal, cardiac
      or cerebrovascular complications during the fourth or fifth decade of life.
      Enzyme replacement therapy is a major advance in the treatment of rare diseases.
      In 2001 two formulations have been approved by the European Medical Evaluation
      Agency, agalsidase alpha and agalsidase beta. Agalsidase alpha is produced on the
      human fibroblast cell line, and agalsidase beta from the Chinese hamster ovary
      cell line.

PMID- 16802574
TI  - [Severe respiratory distress due to ileal duplication cyst in the newborn].
AB  - Differential diagnosis of neonatal respiratory distress includes pulmonary and
      systemic disorders and anatomic problems compromising respiratory system. We
      report on a 2770-g female born to a 29-year-old gravida 3, para 2 woman after 34
      weeks of gestation. Antenatal ultrasound performed in week 8 and 21 was normal.
      The infant was delivered by cesarean section after amniotic membranes had been
      ruptured for less than 12 hours due to signs of fetal distress. The Apgar score
      was 3 and 3 at 1 and 5 minutes, respectively. The infant was intubated and
      resuscitated, and transferred immediately to the neonatal intensive care unit.
      She had an extremely protuberant and cyanotic abdomen. Dilated cutaneous
      collateral vessels were apparent in the periumbilical region. Abdominal
      sonography showed cystic multiloculated tumorous mass filled with dense,
      flocculent content at the level of hepatic portal. The tumorous mass occupied the
      majority of the abdomen with caudal extension toward the pelvis and dorsally
      toward the spine. The liver was displaced high under the diaphragm with the left
      liver lobe in the left hemiabdomen. On x-ray the lung were collapsed due to a
      large abdominal mass in the right hemiabdomen that displaced the right diaphragm
      and intestines contralaterally. She soon developed bilateral pneumothoraces.
      Drainage and continuous suction were started. The infant failed to improve
      despite all attempts and died. On autopsy, an extremely large, mobile,
      multichambered, solitary cyst was found. It was attached to the mesenteric side
      of the ileum by its own thin peduncular stalk and had no communication with the
      remainder of the gut. It occupied the majority of the abdomen. Histologic section
      revealed a well-developed smooth muscle wall and inner mucosa of small bowel
      type. Respiratory distress is a common problem in premature infants. The majority
      of cases are due to pulmonary disorders (e. g., hyaline membrane disease,
      meconium aspiration syndrome, pneumonia), hypothermia, metabolic acidosis,
      anemia, and congenital heart disease. Anatomic problems including space occupying
      lesions are less common. Duplications of the alimentary tract in infants and
      children are rare congenital anomalies. Although symptoms can occur at any age,
      they usually present during the first year. In our patient, intraabdominal mass
      caused severe respiratory distress and respiratory failure in the first hours of
      postnatal life. This had been seen before only as a complication of intrathoracic
      lesions extending into the abdominal cavity. Pathology revealed spherical
      intestinal duplication that was completely separated from the alimentary tract.
      Embryologically, it was a localized duplication. Respiratory distress in our
      patient was refractory to all means of mechanical ventilation. Poor lung
      compliance was the consequence of prenatal lung hypoplasia and inadequate
      postnatal lung expansion due to the duplication cyst space occupying character
      and its compressive effect. Prenatal diagnosis was the child's only chance for
      survival but it was not made. Duplications of the alimentary tract can present a
      diagnostic challenge even in the first hours of life. They should be included in
      the differential diagnosis of severe respiratory distress, especially in
      premature infants in which timely prenatal diagnosis cannot be always made. We
      propose their inclusion among other space occupying lesions that might be the
      cause of severe respiratory distress even in the earliest neonatal period.

PMID- 16802575
TI  - [Uveitis caused by Toxocara canis].
AB  - The course of disease in a 64-year-old man with toxocariasis and ocular
      manifestations of the disease, treated at Departments of Ophthalmology and of
      Infectious Diseases, Dr. Josip Bencevic General Hospital in Slavonski Brod,
      Croatia, is presented. The patient was hospitalized for bilateral uveitis of
      unknown etiology. In several days, the patient developed high fever with
      respiratory tract involvement and hepatomegaly. Worsening of the patient's
      general condition and laboratory findings of leukocytosis and eosinophilia
      indicated clinical examinations for parasitosis, in consultation with a
      specialist for infectious diseases. Specific serologic testing pointed to
      toxocariasis. The patient's general condition and ophthalmologic status improved
      in response to specific therapy with anthelmintics and corticosteorids.
      Toxocariasis is an acute infectious disease that primarily affects animals and
      less frequently humans. Clinically, toxocariasis manifests as a systemic disease,
      and on the eye as parasitic posterior uveitis. The disease is caused by the
      nematodes Toxocara canis and Toxocara cati, the species parasitic in the
      intestine of dogs and cats, respectively. When the parasite eggs reach human
      intestine, larvae are released and migrate via blood and lymphatic system to the
      liver, lungs, eyes, and other organs. Considering the mechanism of disease
      transmission, the potential preventive measures should include treatment and
      appropriate anthelmintic management of infected animals, and due control of
      public areas such as public gardens, promenades, playgrounds, along with taking
      pets for exercise to the sites specially intended for this purpose.

PMID- 16802576
TI  - [Coronary artery surgery in women].
AB  - Cardiovascular diseases are the leading cause of morbidity and mortality for
      women in developed countries. Numerous studies have shown that women have higher
      morbidity and mortality rates than men following coronary artery bypass graft
      surgery (CABG). Having this evidence as our starting point, we compared the
      outcomes of CABG procedures in women and men. The analysis included patient
      preoperative risk factors (age, left ventricular ejection fraction, diabetes
      mellitus, arterial hypertension, hypercholesterolemia, myocardial infarction and
      cerebrovascular insult), number of grafts and perioperative complications
      (reopening for bleeding, perioperative myocardial infarction, sternal wound
      infections--both superficial and deep, atrial and ventricular fibrillation,
      cardiac decompensation), and mortality. Women had more risk factors and
      comorbidities than man, including arterial hypertension and hypercholesterolemia,
      but less severe atherosclerosis and higher left ventricular ejection fraction.
      Off-pump myocardial revascularization was done in 48% of women and in 42% of men.
      There was no statistically significant difference in perioperative complications
      between women and men. Comparison of the mean values showed the perioperative
      mortality to be higher in women than in men (3.4% vs. 2.9%), but the difference
      was not statistically significant (p = 0.724).

PMID- 16802577
TI  - [Obstruction icterus--our experience].
AB  - INTRODUCTION: The most common causes of extrahepatic obstruction are
      choledocholithiasis, malignant and benign stenosis of biliary ducts, pancreatic
      head carcinoma, and chronic cephalic pancreatitis. Differentiation between
      hepatocellular icterus with intrahepatic obstruction and extrahepatic mechanical
      obstruction is of utmost importance. Differential diagnosis usually includes a
      combination of clinical examination, biochemical testing, ultrasonography,
      endoscopic retrograde cholangiopancreatography (ERCP), transhepatic
      cholangiography, computed tomography (CT), nuclear magnetic resonance (NMR) and
      endoscopic ultrasonography (EUS). Choledocholithiasis mostly develops due to
      concrement migration from the gallbladder. The treatment of choice is operative
      therapy by either conventional method with laparotomy or endoscopic concrement
      extraction, the latter being preferred in case of residual concrements. Malignant
      stenoses of extrahepatic ducts can involve any segment of the biliary ducts or
      the gallbladder. The main symptom is so-called painless icterus. The condition is
      treated surgically by radical (various types of resection) or palliative
      (biliodigestive anastomoses) methods. Intraoperative lesion occurring on biliary
      duct procedures is generally involved in the etiology of benign stenoses of
      extrahepatic biliary ducts. The treatment is surgical and consists of the
      creation of hepaticojejunal anastomosis. PATIENTS AND METHODS: The study included
      151 patients admitted during a 5-year period (1999-2003) to Department of
      Surgery, Zabok General Hospital. Icterus was caused by choledocholithiasis in
      112, carcinoma of extrahepatic biliary ducts in seven, carcinoma of the
      gallbladder in five, and carcinoma of the head of pancreas in 18 patients.
      Cephalic pancreatitis, malposition of a clamp placed during laparoscopic
      procedure, postoperative choledochus stricture, stricture of choledochoduodenal
      anastomosis and multiple cystic liver disease caused icterus in nine patients. In
      106 choledocholithiasis patients, the concrement was removed by
      choledocholithotomy; duodenotomy and papillotomy in addition to choledochotomy
      were required in four patients; and creation of biliodigestive anastomosis was
      needed in two patients due to impossible concrement removal. Biliodigestive
      anastomosis was created in another 20 patients with the findings of inoperable
      tumor of the head of pancreas, inoperable tumor of the papilla of Vater,
      postoperative choledochus stenosis, stenosis of choledochoduodenal anastomosis,
      and chronic cephalic pancreatitis. Cephalic duodenopancreatectomy was performed
      in two patients, whereas other methods consistent with the etiologic substrate
      were employed in 17 patients. The following complications were observed in 151
      patients operated on: T drain fall off (n = 2), lesion of retroduodenal
      choledochus (n = 1), and loosening of the cholecystojejunal anastomosis suture
      line (n = 1). The hospital mortality rate was 3.31% (n = 5). DISCUSSION:
      Impairment in the biliary duodenal drainage is an etiologic factor in the
      development of obstructive icterus. It is of utmost importance to differentiate
      hepatocellular icterus with intrahepatic obstruction from extrahepatic mechanical
      obstruction. The treatment depends on the etiologic factor involved. Operative
      treatment can be fully successful in cases caused by lithiasis or benign
      stenosis, whereas in cases due to malignant disease a variety of radical and
      operative procedures associated with a variable level of success are available.
      CONCLUSION: Mechanical obstructive icterus of extrahepatic biliary ducts ranks
      high in the morbidity and mortality in the Krapina--Zagorje County. Timely
      diagnosis, well planned and properly performed operative procedures could
      considerably improve the results achieved by the operative treatment of the
      disease.

PMID- 16802578
TI  - Does pesticide risk assessment in the European Union assess long-term effects?
AB  - Current methods would allow reasonable predictions of long-term effects of
      pesticide application if three changes were instituted. First, more population
      based laboratory studies should be applied in predictive pesticide risk
      assessment. Second, ERA should include as much effort on collating and
      integrating ecological knowledge into the assessment in Tier 1 as is currently
      expended on gathering chemical and toxicological information on exposure and
      effects. Production of a formal conceptual ecological risk assessment model for
      each product or active substance for which authorization is sought would provide
      an appropriate framework for integrating and applying such knowledge. Third, in
      acknowledgment of the uncertainties in the predictive risk assessment process,
      more postauthorization monitoring should be done. The application of Occam's
      razor to pesticide risk assessment makes good sense, as it does in any other
      field of science. However, we must take care that simplicity in risk assessment
      process does not lead to oversimplification: Essentially all science is the study
      of either very small bits of reality or simplified surrogates for complex whole
      systems. How we simplify can be critical. Careless simplification leads to
      misleading simplistic conclusions. (Slobodkin 1994).

PMID- 16802579
TI  - Sulfonamides in the environment as veterinary drugs.
AB  - SAs, a structurally related group of antibiotics containing a similar 4
      aminobenzene sulfonamide backbone, are used in agriculture, aquaculture, animal
      husbandry, and also as human medicines. Competing with p-aminobenzoic acid in the
      enzymatic synthesis of dihydrofolic acid, SAs inhibit the growth and reproduction
      of bacteria. Once released to the environment, SAs distribute themselves among
      different environmental compartments, along with their degradation products, and
      are transported to surface water and groundwater. The physicochemical properties,
      the dosage applied and the nature of the environmental components with which they
      interact, govern the whole process. SAs, as a class, are less sorptive,
      impersistent, and leachable. They cannot be characterized as readily
      biodegradable. Their adsorption to soil increases with the aromaticity and
      electronegativity of functional groups attached to the sulfonyl phenyl amine
      core. Preferential flow in clay soils has been identified as a mechanism
      responsible for surface water contamination by SAs.

PMID- 16802580
TI  - Terminology of gonadal anomalies in fish and amphibians resulting from chemical
      exposures.
AB  - Given the recent increase in the number of studies describing the ability of
      chemicals to exert endocrine-disrupting effects, not only in fish but in a
      variety of other oviparous groups such as amphibians and reptiles, there is an
      urgent need to harmonize the terminology currently used in describing
      pathological changes of the gonads. In addition to difficulties in comparing
      results from different studies, there is also the risk of miscommunication by
      using terms that imply a certain clinical relevance which may not be true for the
      species examined. Especially in the case of the recent and controversial issue
      about potential effects of the triazine herbicide atrazine on amphibians,
      clinical terminology has been utilized beyond its true meaning by using terms
      such as "chemical castration" to describe occurrence of TOs or ovarian tissue in
      the testis of male frogs exposed to environmental chemicals (Hayes 2004). In
      clinical terminology, castration is defined as the removal of the gonads or their
      destruction by an external influence, resulting in a nonfertile organism.
      However, Hayes (2004) did not investigate any possible effects on the fertility
      of the test animals and thus did not know if these animals were truly castrated.
      Similarly, terms such as intersex, hermaphrodite, and sex reversal have been used
      in ways that appear inappropriate with regard to their clinical meaning in a
      series of different studies with fish or frogs (see previous sections for a
      detailed discussion). To ensure the appropriate use of certain terminology in a
      field as controversial and complex as the study of endocrine disruption, we have
      attempted, in this chapter, to harmonize the terminology used to describe changes
      in gonadal development of vertebrates such as fish and amphibians, especially
      frogs (see Table 3). Where appropriate, the terminology suggested was adopted
      directly from the clinical terminology. However, as outlined here there are
      substantial differences between the developmental biology of oviparous
      vertebrates and mammals, and especially humans, that necessitate modification of
      the definitions of some of the clinical terms. Where appropriate, therefore, the
      terminology proposed in this manuscript was redefined based on the biological
      meanings of the terms used in clinical diagnosis. Considering the large increase
      in research in the area of reproductive endocrine disruption over the past
      decades, the authors see an increasing need for a harmonization of terms to be
      used to describe effects observed in the investigated species. Agreement on a
      common terminology will allow scientists to better communicate and compare their
      work, and will enable risk assessors to conduct large-scale evaluations of
      environmental endocrine disruption by fitting the information from individual
      studies into a synthesis of normal and abnormal conditions of gonadal tissues.

PMID- 16802581
TI  - Behavior of pesticides in water-sediment systems.
AB  - Many experimental reports on the fate of pesticides in either laboratory or
      outdoor water-sediment systems have been obtained from both research and
      regulatory aspects that show some trends in distribution and degradation for each
      chemical class of pesticides. Adsorption, diffusion, hydrolysis, and
      biodegradation processes are important in controlling the behavior of pesticides
      in these water-sediment systems. Through these investigations, the contribution
      of suspended particles and dissolved organic matter has become more accepted in
      relation to these processes. Not only the physicochemical properties and
      degradability of a pesticide but also the characteristics of the many phases
      composing a water-sediment system determine the actual pesticide behavior, and
      therefore we should appropriately design an experimental system by considering
      the real situation of the natural aqueous environment to be examined. Many
      factors controlling experimental results in a laboratory system such as water
      sediment ratio, depth of water and sediment phases, and mixing of water column
      have been clarified; however, there are still many issues to be examined. For
      example, a pesticide is always used as a formulation, but its effects on
      pesticide behavior in a water-sediment system have not been extensively examined.
      When its behavior in a natural aquatic system is considered, the effect and
      importance of photolysis are necessary to examine as an individual degradation
      process, but photolysis has been only briefly discussed in outdoor microcosm and
      mesocosm studies. Many studies discuss the distribution and degradation pathways
      of a pesticide, but its transport between water and sediment phases has scarcely
      been investigated because of its complexity, especially for a pesticide that is
      moderately or easily degraded in a water-sediment system. This form of
      investigation would be very useful when metabolites or degradates having more
      toxicological impact on aquatic species and sediment dwellers are found. From
      this point of view, the behavior of a pesticide and its metabolite(s) in an
      interstitial sediment porewater should become another critical point to be
      examined in the future. Other issues to be investigated further are the relevant
      processes in the neighborhood of interfaces. In an air-water interface, the
      effect of a surface microlayer has been examined mainly through microcosm and
      mesocosm studies, but the contribution of interfaces to either volatilization or
      photodegradation should be examined in more detail to precisely estimate
      dissipation profiles of a pesticide in the real aquatic environment. Furthermore,
      the enrichment of a pesticide in this interface should be investigated in
      relation to an emergence of chironomids. Recently, many kinetic approaches have
      been attempted to more effectively use experimental data in prediction of the
      fate of a pesticide by the aid of a simulation model. Most existing rate data
      usually represent apparent dissipation rates but not degradation rates, and
      therefore separation of the degradation rate from dissipation by considering
      adsorption-desorption and transport processes would be of immense value.

PMID- 16802583
TI  - Pregnant pause for teenage mums.

PMID- 16802584
TI  - World Cup fever.

PMID- 16802585
TI  - Hungry for help.
AB  - While obesity is the hot topic in dietetics, malnutrition costs the NHS far more.
      Recent guidelines from the National Institute for Health and Clinical Excellence
      (NICE) have addressed the problem but with the NHS strapped for cash, it is
      unlikely to be a high priority. Older people, especially those with long-term
      conditions, are vulnerable to malnutrition. Malnutrition is estimated to cost the
      UK pounds 73 billion a year. Malnourished people take longer to recover from
      illness and are more prone to complications.

PMID- 16802586
TI  - Get with the program.
AB  - For those who find it tough to stick to a healthy lifestyle, help is at hand.
      Desktop DAN--an animated computer program from the British Dietetic Association
      and Canned Food UK--will pop up on your computer screen and offer messages to
      strengthen your resolve.

PMID- 16802587
TI  - Hidden hatreds.

PMID- 16802589
TI  - Addressing problematic behaviour in learners.

PMID- 16802588
TI  - Under-reporting of violent incidents against nursing staff.
AB  - This article examines factors that contribute to nurses failing to report
      incidents of violence and aggression in the clinical area and it develops the
      information published in a previous article (Ferns and Chojnacka 2005). Broader
      social factors are considered, including gender, violence experienced by women,
      the status of the nursing profession and bureaucratic structures that contribute
      to under-reporting. The life experiences of individual nursing staff play a
      significant role in how they react to violence in the clinical area. Strategies
      to minimise violence against nurses should consider the social, political and
      personal issues that limit the reporting of violent incidents. Only by reporting
      such incidents can the extent of violence towards nurses be determined and
      minimised.

PMID- 16802590
TI  - The risk of infection from toys in the intensive care setting.
AB  - The risk of cross-transmission of infection for patients in intensive care is
      substantial. The increasing use of new technologies and invasive procedures
      increases the risk of acquiring a healthcare-associated infection. The routine
      and effective disinfection of toys, unlike other equipment, is often overlooked
      and research into toys as a potential source of infection is sparse. A small
      scale study measured the prevalence of micro-organisms on toys in the intensive
      care setting. It was conducted in a paediatric intensive care unit (ICU) at a
      large teaching hospital but the results will have resonance with adult ICUs. The
      study involved swabbing toys that had been brought in by families and those that
      were provided by the hospital. Recommendations for future practice are identified
      to ensure that toys can still be made available in hospital and are safe in
      relation to the transmission of infection.

PMID- 16802592
TI  - Diabetes in South Asian communities.

PMID- 16802591
TI  - Prevention and control of infection in non-acute healthcare settings.
AB  - This article discusses the main principles of infection prevention and control in
      non-acute healthcare settings. It explores the use of a set of ten tools
      developed by the Infection Control Nurses Association (ICNA) to audit infection
      prevention and control, using the standard statements and criteria within the
      tools as a checklist. The results of the audit of facilities, commodities and
      practice using the ICNA audit tools will help staff to identify areas of best
      practice and areas where improvements are needed to enhance patient care.

PMID- 16802593
TI  - Researching questions.

PMID- 16802594
TI  - Step up to success.

PMID- 16802595
TI  - Protein kinase C-theta (PKCtheta): new perspectives on its functions in T cell
      biology.

PMID- 16802596
TI  - Travel informations on the Tec kinases during lymphocyte activation.

PMID- 16802597
TI  - Inducible T cell tyrosine kinase (ITK): structural requirements and actin
      polymerization.

PMID- 16802598
TI  - Differential requirements of PI3K subunits for BCR or BCR/CD19-induced ERK
      activation.

PMID- 16802599
TI  - Protein tyrosine phosphatases in human disease.

PMID- 16802600
TI  - The T cell-specific adapter protein functions as a regulator of peripheral but
      not central immunological tolerance.

PMID- 16802601
TI  - Proximal signals controlling B-cell antigen receptor (BCR) mediated NF-kappaB
      activation.

PMID- 16802602
TI  - The adapter 3BP2: how it plugs into leukocyte signaling.

PMID- 16802603
TI  - CTLA-4 regulation of T cell function via RAP-1-mediated adhesion.

PMID- 16802604
TI  - Protein crosstalk in lipid rafts.

PMID- 16802605
TI  - Role of lipid rafts in activation-induced cell death: the fas pathway in aging.

PMID- 16802606
TI  - T cell response in aging: influence of cellular cholesterol modulation.

PMID- 16802607
TI  - Lymphocyte signaling and the translatability of mRNA.

PMID- 16802608
TI  - Protein arginine methylation: a new frontier in T cell signal transduction.

PMID- 16802609
TI  - Immune regulation by ubiquitin conjugation.

PMID- 16802610
TI  - CTIB (C-Terminus protein of IkappaB-beta): a novel factor required for acidic
      adaptation.

PMID- 16802611
TI  - HIV may deplete most CD4 lymphocytes by a mechanism involving signaling through
      its receptors on non-permissive resting lymphocytes.

PMID- 16802612
TI  - Integrating traditional and postgenomic approaches to investigate lymphocyte
      development and function.

PMID- 16802613
TI  - Phosphoproteomic analysis of lymphocyte signaling.

PMID- 16802614
TI  - Warfare and the state of the world's children.

PMID- 16802615
TI  - How do we treat children with severe malaria?

PMID- 16802616
TI  - The neglected tropical diseases: the ancient afflictions of stigma and poverty
      and the prospects for their control and elimination.

PMID- 16802617
TI  - Viral haemorrhagic fevers caused by Lassa, Ebola and Marburg viruses.

PMID- 16802618
TI  - Rotavirus and rotavirus vaccines.
AB  - Two new rotavirus vaccines have recently been licensed that will provide the
      intervention needed to diminish the huge burden of rotavirus disease among all
      children. In many upper and middle income countries, these vaccines will soon be
      available for the routine immunization of children. The impact should be a rapid
      and measurable reduction in hospitalizations and doctor visits for acute diarrhea
      in children, especially in the winter rotavirus season. While few deaths occur in
      these settings, the illness has consequences in terms of both medical costs and
      indirect costs, including parents work time lost. In the developing world,
      clinical trials are still needed to ensure that the vaccines being licensed will
      work as expected in children living in poor settings. In these settings, other
      enteric flora, micronutrient malnutrition, higher titers of maternal antibody and
      other factors still poorly defined have compromised other live oral vaccines and
      have required the developers to alter vaccine formulation, dose, or schedule.
      Until these trials are completed, we can only hope that the efficacy will be
      comparable and that the vaccine will prove to be life-savers. Once the efficacy
      and safety have been established, rotavirus vaccines could provide a major boost
      to programs for child survival.

PMID- 16802619
TI  - Transient deficiencies of T-cell-mediated immunity in the neonate.

PMID- 16802620
TI  - Controversies in neonatal sepsis: immunomodulation in the treatment and
      prevention of neonatal sepsis.

PMID- 16802621
TI  - Chlamydia trachomatis genital infection in adolescents and young adults.

PMID- 16802622
TI  - The role of inflammation and infection in the development of chronic lung disease
      of prematurity.
AB  - CLD is a significant cause of infant morbidity and mortality. The lung injury is
      multifactorial in origin with supplemental oxygen and ventilatory damage being
      only part of the picture. Antenatal and postnatal infection and inflammation are
      also important in the development of CLD, although their precise role has still
      to be fully ascertained. In the future, therapeutic strategies need to be
      considered to decrease the incidence and severity of CLD. In particular a
      definitive trial investigating the role of antibiotics against Ureaplasma
      urealyticum in preventing CLD needs to be performed. Increased use of newer
      microbiological methods will also improve our understanding of the role of
      infection in CLD and further guide research and clinical management.

PMID- 16802623
TI  - Streptococcus pneumoniae: infection, inflammation and disease.

PMID- 16802624
TI  - Impact of antimicrobial resistance on therapy of bacterial pneumonia in children.

PMID- 16802625
TI  - Diagnosis and prevention of pneumococcal disease.

PMID- 16802626
TI  - New antibiotics for Gram-positive infections.

PMID- 16802627
TI  - Clinical manifestations of nontuberculous mycobacteria.

PMID- 16802628
TI  - Kingella kingae: an emerging pediatric pathogen.

PMID- 16802629
TI  - How to treat acute musculoskeletal infections in children.
AB  - Timely diagnosis of musculoskeletal infections is essential to prevent severe
      complications of this disease. Important symptoms that lead to the diagnosis
      include high fever, malaise, local pain and loss of function of the involved
      extremity. In the case of arthritis, swelling of the affected joint may develop
      quickly in the course of disease. Imaging techniques include ultrasound and MRI.
      Both are useful in determining the exact site of infection. Infectious
      parameters, C-reactive protein and/or sedimentation rate of erythrocytes (ESR)
      are used in following disease activity during treatment. The gold standard for
      diagnosing musculoskeletal infection is microbiological isolation of the
      organism. Bone-biopsy of an involved metaphysis or aspiration of joint-fluid
      gives the highest chance of a positive culture. Usually S. aureus is the
      causative micro-organism, although specific underlying diseases may predispose to
      other bacterial infections. Antibiotic treatment is aimed at the most likely
      causative micro-organism. In some instances surgical treatment is necessary,
      especially in cases of focal and chronic osteomyelitis and when the adjacent
      joint is involved in the inflammatory process. Collaboration between
      paediatrician and orthopaedic surgeon is essential to achieve the best treatment
      for the patient.

PMID- 16802630
TI  - Prevention of transmission of HIV-1 from mothers to infants in Africa.

PMID- 16802631
TI  - Practical aspects of antiretroviral treatment in children.

PMID- 16802632
TI  - Antibiotic treatment for acute otitis media in children.

PMID- 16802633
TI  - Antibiotic prophylaxis for the prevention of recurrent urinary tract infections
      in children.

PMID- 16802634
TI  - Human metapneumovirus: an important cause of acute respiratory illness.

PMID- 16802635
TI  - If you have it on the shelf, you can deliver it.

PMID- 16802636
TI  - DIAGNOdent measurements and correlation with the depth and volume of minimally
      invasive cavity preparations.
AB  - In this clinical study, DIAGNOdent (KaVo) was used to assess previously diagnosed
      carious lesions in the pits and fissures of first and second molars. The
      measurements from this device were correlated with the depth and volume of the
      cavity preparations that resulted from minimal intervention to remove occlusal
      carious lesions. Twenty-five patients, 18 years of age and older, who were
      previously scheduled for an occlusal restoration due to caries, were recruited
      and enrolled in this clinical study. These patients had 48 qualifying teeth
      without previous restorations, sealants or other carious lesions. The occlusal
      surface of each study tooth was cleaned utilizing ProphyFlex2 (KaVo). Two
      dentists separately traced the pit and fissure system of each tooth using
      DIAGNOdent for two 15-second periods each. The peak reading of each of the four
      measurements was recorded. An impression of the occlusal surface of each tooth
      was recorded with a polyvinyl siloxane bite registration material. The carious
      lesions were removed with an air abrasion unit employing a 0.015-inch nozzle
      opening utilizing minimal operative intervention. A low viscosity polyvinyl
      siloxane was used to take an impression of the cavity preparation impression,
      using the bite registration impression to form the occlusal surface of the
      preparation impression. The preparation impression volume was calculated from its
      weight, using the known density of the impression material. The greatest depth of
      the preparation was measured. The Pearson correlation coefficient was used to
      investigate any relationship between depth or volume of the preparation
      impression and the DIAGNOdent measurements. The correlation for preparation
      volume and maximum DIAGNOdent measurement was 0.191 (p = 0.189). Other logical
      subsets of cases also did not result in any statistically significant
      correlations between the DIAGNOdent readings and the depth or volume of the final
      cavity preparations.

PMID- 16802637
TI  - Direct pulp capping with a dentin bonding system in human teeth: a clinical and
      histological evaluation.
AB  - This study evaluated the pulpal response in human dental pulp to direct pulp
      capping with the Single Bond Adhesive System (SBAS) after 10% or 37% phosphoric
      acid etching and after capping with Calcium Hydroxide (CH). The degree of
      bleeding and hemostasis conditions was considered during the adhesive technique.
      The pulps of 78 sound premolars were capped with SBAS after 37% phosphoric acid
      etching (Group I) or 10% phosphoric acid etching (Group II) and CH (Group III
      control). The cavities were restored with a resin composite (Charisma). After 1,
      3, 7 and 30 days, the teeth were extracted and processed for light microscopical
      examination (H/E, AgNOR silver stain and Brown-Brenn). The patients were followed
      for postoperative symptomatology evaluation. Clinical results showed the
      possibility of hemostasis with saline solution only. There was no statistical
      difference between bleeding generated by 10% and 37% acid solutions. In some
      cases, contact of the pulp tissue with SASB started the bleeding process, thus
      damaging the adhesive technique. The histological response was similar in Groups
      I and II, without signs of cellular differentiation and dentin neoformation up to
      30 days. Bacteria were not observed in any specimens. In the control group (CH)
      at day 7, the pulps exhibited cells with high synthetic activity (Ag-NOR
      positive) underneath the area of coagulation necrosis. Dentin bridging was
      observed at the thirtieth day. The postoperative period was asymptomatic for all
      groups. In conclusion, SBAS should be avoided for vital pulp therapy, while CH
      remains the capping agent of choice for mechanically exposed human dental pulp.

PMID- 16802638
TI  - Randomized clinical trial on the efficacy of a new bleaching lacquer for self
      application.
AB  - BACKGROUND: This study evaluated the clinical efficacy and duration of
      effectiveness of a new bleaching lacquer for self-application without the use of
      mouth guards. It compared two different application times. METHODS: Forty-six
      adult subjects who requested bleaching treatment were selected to participate in
      this randomized, single-blind (examiner-blinded), single center, two-group trial.
      The subjects were randomly divided into two groups (n=23 each), each being
      instructed to bleach (8% carbamide peroxide) their six maxillary anterior teeth
      for two weeks. Daily contact time in Group 1 was 20 minutes once a day and, in
      Group 2, the time was 20 minutes twice a day. Efficacy was measured subjectively
      using the Chromascop Complete shade scores obtained at baseline and after one,
      two and three weeks, as well as after one, three, six and nine months. RESULTS:
      After two weeks of treatment, the teeth in the Group 1 subjects exhibited a 2.4
      +/- 0.2 mean shade scores improvement compared to baseline (p < 0.001; t-test for
      paired samples), and the subjects' teeth in Group 2 exhibited a 3.5 +/- 0.1 mean
      shade scores improvement (p < 0.001). However, the difference between both groups
      was not statistically significant (p > 0.05). The observed effects were stable
      for six months. CONCLUSIONS: It can be concluded that the new bleaching lacquer
      is efficacious; however, a double application does not seem to be obligatory.

PMID- 16802639
TI  - Effect of different bur grinding on the bond strength of self-etching adhesives.
AB  - This study compared the microtensile bond strength (MTBS) of three all-in-one
      adhesive systems and a two-step system using two types of burs to prepare the
      dentin surfaces. Flat coronal surfaces of 24 extracted human molars were produced
      using either regular-grit or superfine-grit diamond burs. Resin composite was
      then bonded to equal numbers of these surfaces using one of the four adhesives:
      Clearfil SE Bond (CSE), G-Bond (GB), SSB-200 (SSB) or Prompt L-Pop (PLP). After
      storage for 24 hours in 37 degrees C distilled water, the bonded teeth were
      sectioned into slices (0.7-mm thick) perpendicular to the bonded surface. The
      specimens were then subjected to microtensile testing and the bond strengths were
      calculated at failure. Bond strength data were analyzed by two-way ANOVA and the
      GamesHowell test for interaction between adhesive and type of cut dentin. The
      fractured surfaces were observed by SEM to determine the failure mode. In
      addition, to observe the effect of conditioning, equal numbers of the two bur-cut
      dentin surfaces of eight additional teeth were conditioned with the adhesives and
      observed by SEM. Based on the results, when CSE and SSB were bonded to dentin cut
      with a regular-grit diamond bur, the MTBS values were significantly lower than
      that of superfine bur-cut dentin; whereas, GB and PLP showed no significant
      differences in MTBS between the two differently cut surfaces. SEM observation of
      the fractured surfaces revealed a mixed mode (adhesive in some areas and cohesive
      in others in the same sample) of failure in all specimens except PLP, which
      showed cohesive failure within the adhesive for both types of bur preparation.
      Generally, SEMs of the conditioned surfaces using both types of burs showed
      partial removal of the smear layer for CSE, minimal for GB and SSB and complete
      removal for PLP. In conclusion, when cutting dentin, selecting the proper bur
      type is important for improving the bond strength of some self-etching adhesive
      systems.

PMID- 16802640
TI  - Step-cure polymerization: effect of initial light intensity on resin/dentin bond
      strength in class I cavities.
AB  - This in vitro study assessed the effect of a step-cure light curing method on
      resin/dentin bond strength on the buccal wall of Class I cavities in human teeth.
      Occlusal enamel was removed to expose a flat dentin surface. Twenty four box
      shaped cavities (C-factor = 4.5) were prepared in dentin. Prime&Bond 2.1 was
      applied and TPH Spectrum (Dentsply) was inserted using a bulk-filling increment.
      The composite was light-cured using either a step-cure photoactivation technique
      or a one-step continuous curing method. For step-cure polymerization, the initial
      cure intensity was varied by changing the distance between the light source and
      the resin surface. The light-cured resins were cured using four low light
      intensities: 150(G1), 200(G2), 250(G3) and 300(G4) mW/cm2. In the continuous
      exposure curing method, the samples were light-activated for 40 seconds at 740
      mW/cm2 and irradiation was applied in a box-shaped cavity and a flat cavity
      (exposed buccal wall, C-factor = 0.22). Samples were prepared for TBS testing by
      creating bonded beams (of approximately 0.8 mm2) obtained from the buccal wall.
      The data were analyzed using one-way ANOVA, Tukey Test and Dunnett's Test at a
      significance level of 0.05. The mean TBS values for the continuous exposure group
      in the flat and box-shaped cavities were 24.31 and 10.23 MPa, respectively. The
      corresponding TBS for step-cure polymerization was 23.13 (G3), 18.83 (G2), 14.87
      (G1) and 13.26 MPa (G4). Bond strength values to the cavity wall were lower in
      the three-dimensional cavities and dependent on the light curing method (p <
      0.05). The use of a low initial light intensity (200-250 mW/cm2) for 10 seconds
      followed by high irradiation intensity provided the best bond strengths, similar
      to bonding in a flat cavity.

PMID- 16802641
TI  - The microtensile bond strength of self-etching adhesives to ground enamel.
AB  - It is uncertain whether single-phase self-etching adhesives form bonds to enamel
      as reliable as those of etch-and-rinse adhesives. This study compared the
      microtensile bond strengths to ground enamel of three self-etching adhesive
      systems, a self-etching primer system and an etchand-rinse adhesive system. Human
      enamel was ground flat with 320-grit silicone carbide paper. The self-etching
      adhesives iBond (Heraeus Kulzer), Prompt L-Pop (3M ESPE) and Xeno III
      (Caulk/Dentsply), the adhesive with a self-etching primer Clearfil SE Bond
      (Kuraray) and the etch-and-rinse adhesive Scotchbond Multipur-pose (3M/ESPE) were
      applied as directed, followed by a core of the same manufacturers' hybrid resin
      composite. A microtensile bond strength evaluation was performed after 48 hours
      of water storage, using untrimmed beams approximately 0.9 mm2 in cross-sectional
      area at a crosshead speed of 0.6 mm/minute. There were no pretest failures in any
      group, and failures were predominately adhesive or mixed. Adhesion to enamel of
      Clearfil SE was not significantly different from Scotchbond Multi-Purpose, while
      the three self-etching adhesive systems demonstrated significantly lower bond
      strengths (One-way ANOVA, Tukey-Kramer Multiple-Comparison Test, p < 0.00001).

PMID- 16802642
TI  - Inhibition of lesion progression by the penetration of resins in vitro: influence
      of the application procedure.
AB  - This study compared the progression of sealed initial enamel lesions penetrated
      with a fissure sealant (Helioseal, Vivadent) or various adhesives (Heliobond,
      Excite, Vivadent; Resulcin, Merz; Solobond M, Voco; Prompt L-Pop, 3M-ESPE) after
      exposure to a demineralizing solution, in vitro. From 27 bovine teeth, 54 enamel
      specimens were prepared and covered with nail varnish (control), thus obtaining
      three windows for treatment. After demineralization (pH 5.0; 14 days), two of the
      windows (A, B) were etched with phosphoric acid (20%; 5 seconds); whereas, the
      third area served as the control (C). The specimens were divided randomly into
      six groups (n=9), and the material was applied (90 seconds) either once (A) or
      twice (B). Light-curing followed each application. Half of the area of each
      specimen window was then covered with nail varnish, and the samples were again
      stored in the demineralizing solution (pH 5.0; 14 days). The specimens were cut
      perpendicular to the surface, and both enamel slabs were studied after
      infiltration using a fluorescent, low viscous resin (VIRIN) and confocal
      microscopy (CLSM). Lesion depths were calculated (ImageJ) from the surface to
      that point in the lesion where the grey values clearly changed to a darker grey.
      After demineralization, mean lesion depths (SD) (14 days) were measured at 105
      (21) microm. The second demineralization led to a mean progression of the lesion
      depths of 52 (31)%. Adper Prompt L-Pop and Solobond M could not significantly
      prevent lesion progression after a single application (p > 0.05; t-test);
      however, the second application of Solobond M significantly decreased lesion
      progression (p < 0.05; t-test). Helioseal, Heliobond, Resulcin Monobond and
      Excite showed significantly better inhibition of the demineralization compared to
      the other materials (p < 0.05; Bonferroni). It can be concluded that the
      penetration of adhesives into initial lesions inhibited a further
      demineralization in vitro.

PMID- 16802643
TI  - Quantitative comparison of the water permeable zone among four types of dental
      adhesives used with a dual-cured composite.
AB  - This study compared silver penetration in the adhesive interface among four
      versions of adhesives from the same manufacturer: OptiBond FL, OptiBond Solo
      Plus, OptiBond Solo Plus Dual Cure, and OptiBond Solo Plus Self-Etch, when
      coupled with dual-cured composite, CoreRestore 2 (Kerr). Twenty flat dentin
      surfaces were prepared using one of the adhesives and bonded with the composite,
      following the manufacturer's instructions. The surfaces were sectioned into 2-mm
      slabs and immersed in ammoniacal silver nitrate for 24 hours. Each specimen was
      exposed to a photodeveloping solution for eight hours and examined with a
      scanning electron microscope (SEM). The water permeable area occupied by the
      silver nitrate tracer was determined, and the relative weight of silver was
      analyzed by wavelength dispersive spectrometry (WDS). The OptiBond FL group had a
      significantly lower silver content than the other groups (p < 0.0001). Each group
      demonstrated different patterns of silver deposition within the adhesive layer
      and within various features of artifactual fracture from dehydration stress of
      the SEM. This may be indicative of weak links in the bonded interfaces.
      Simplified-step adhesives showed increased permeability, which can lead to
      disruption of coupling with composites.

PMID- 16802644
TI  - Curing capability of halogen and LED light curing units in deep class II cavities
      in extracted human molars.
AB  - Class II cavities were prepared in extracted lower molars filled and cured in
      three 2-mm increments using a metal matrix. Three composites (Spectrum TPH A4,
      Ceram X mono M7 and Tetric Ceram A4) were cured with both the SmartLite PS LED
      LCU and the Spectrum 800 continuous cure halogen LCU using curing cycles of 10,
      20 and 40 seconds. Each increment was cured before adding the next. After a seven
      day incubation period, the composite specimens were removed from the teeth,
      embedded in self-curing resin and ground to half the orofacial width. Knoop
      microhardness was determined 100, 200, 500, 1000, 1500, 2500, 3500, 4500 and 5500
      microm from the occlusal surface at a distance of 150 microm and 1000 microm from
      the metal matrix. The total degree of polymerization of a composite specimen for
      any given curing time and curing light was determined by calculating the area
      under the hardness curve. Hardness values 150 microm from the metal matrix never
      reached maximum values and were generally lower than those 1000 microm from the
      matrix. The hardest composite was usually encountered between 200 microm and 1000
      microm from the occlusal surface. For every composite-curing time combination,
      there was an increase in microhardness at the top of each increment (measurements
      at 500, 2500 and 4500 microm) and a decrease towards the bottom of each increment
      (measurements at 1500, 3500 and 5500 microm). Longer curing times were usually
      combined with harder composite samples. Spectrum TPH composite was the only
      composite showing a satisfactory degree of polymerization for all three curing
      times and both LCUs. Multiple linear regression showed that only the curing time
      (p < 0.001) and composite material (p < 0.001) had a significant association with
      the degree of polymerization. The degree of polymerization achieved by the LED
      LCU was not significantly different from that achieved by the halogen LCU (p =
      0.54).

PMID- 16802645
TI  - Correlation between the amount of linear polymerization shrinkage and cuspal
      deflection.
AB  - This study evaluated the relationship between the amount of cuspal deflection and
      linear polymerization shrinkage in resin composites and polyacid modified resin
      composites (compomers). Materials included were Dyract AP, Compoglass F, Z100,
      SureFil, Pyramid, Synergy Compact, Heliomolar and Heliomolar HB. To measure
      polymerization shrinkage, a custom-made linometer (R&B, Daejon) was used. Ten
      measurements were made for each group, and the amount of linear shrinkage that
      occurred in 60 seconds was statistically compared by one-way ANOVA analysis and
      Tukey's test. To measure the cuspal deflection of teeth, standardized MOD
      cavities were prepared in extracted maxillary premolars. After a self-etching
      adhesive was applied, the cavities were bulk filled with one of the filling
      materials. Fifteen teeth were used for each material. Cuspal deflection was
      measured by a custom-made cuspal-deflection measuring device. One-way ANOVA
      analysis and Tukey's test were used to determine differences between the
      materials. The correlation of polymerization shrinkage vs cuspal deflection was
      analyzed by regression analysis. The amount of polymerization shrinkage from
      least to greatest was Heliomolar, SureFil < Heliomolar HB < Z100, Synergy Compact
      < Dyract AP < Pyramid, Compoglass F (p < 0.05). The amount of cuspal deflection
      from least to greatest was Z100, Heliomolar, Heliomolar HB, Synergy Compact,
      SureFil, < Compoglass F < Pyramid, Dyract AP (p < 0.05). Both the amount of
      polymerization shrinkage and cuspal deflection were highly correlated (p <
      0.001).

PMID- 16802646
TI  - The effectiveness of alumina powder on carious dentin removal.
AB  - This study determined the size of aluminum oxide particles used in an air
      abrasion system that is able to remove carious dentin tissue with maximum
      preservation of sound structure. Thirty extracted and carious-free third molars
      were used in this study. The dentin sample was obtained by sectioning the middle
      of the crown longitudinal to the long axis of the tooth in a mesio-distal
      direction. One half of the crown corresponded to the sound dentin group (SD),
      while the other half was used to develop artificial caries, constituting the
      carious dentin group (CD). The specimens were air abraded for 15 seconds. The SD
      and CD groups were each randomly divided into three subgroups (N=10) according to
      the particle diameter employed (27, 50 and 125 microm). The prepared cavity was
      perpendicularly cut in half, and the profiles of all hemi-fragments were observed
      using SEM microscopy. The cavity measurements were made using a modified
      cephalometric analysis. The 27, 50 and 125 microm aluminum oxide particles did
      not present selectivity in the removal of carious dentin. However, when using the
      air abrasive technique for carious dentin treatment, the use of 27 and 50 microm
      aluminum oxide particles is recommended, due to their capacity to remove less
      sound tissue than the 125 microm particles.

PMID- 16802647
TI  - Microleakage in conventional and bonded amalgam restorations: influence of cavity
      volume.
AB  - This study verified the relationship between the volume and microleakage of
      conventional and bonded amalgam restorations. Also, the microleakage influence of
      intermediate materials, substrates and the direction of sectioning was
      investigated. Fifty-six bovine incisors were selected. Standard Class V cavities
      were prepared in buccal and lingual surfaces. For each tooth, two cavity sizes
      were prepared, corresponding to two cavity volumes: one larger (A) and the other
      smaller (B). The cervical wall was located in cementum/dentin and the incisal
      wall in enamel. The teeth were distributed in four groups (n=28) according to the
      intermediate material employed (glass-ionomer cement, resin cement, adhesive
      system and copal varnish-control). The materials were applied following
      manufacturers' directions. After restoration, the teeth were submitted to thermal
      cycling. They were then immersed in a dye solution and sectioned in two
      directions inciso-cervical (IC) and mesio-distal (MD) sections to evaluate the
      microleakage. Data were subjected to non-parametric statistical analysis
      (Wilcoxon's paired test and Kruskal-Wallis test). No significant difference was
      found between the two cavity sizes. Leakage in enamel was statistically lower
      than in the cementum/dentin interface (p < 0.05). In some situations, glass
      ionomer or resin cement lined amalgam restorations presented less dye leakage
      than copal varnish lined restorations (p < 0.05). No significant difference was
      observed in microleakage between IC or MD sectioning. Within the limitations of
      this study, it was concluded that cavity size and direction of section were not
      significant factors for microleakage, while substrate and intermediate materials
      had a significant effect on the sealing ability in amalgam restorations.

PMID- 16802648
TI  - Influence of the feldspathic ceramic thickness and shade on the microhardness of
      dual resin cement.
AB  - This study evaluated the microhardness of a dual resin cement under the influence
      of thickness and shade of a feldspathic ceramic. Ninety-five bovine incisors were
      selected; the crowns, with the roots removed, were embedded in a polystyrene
      resin and were randomly divided into 19 groups (n=5). On the buccal surface, a
      standardized cavity, 4.0 mm in diameter and 1.0 mm in depth, was prepared.
      Ceramic restorations (Noritake Ex 3) were manufactured with 4.0 mm diameter and
      1, 2 and 4-mm thicknesses at shades A1, A2, A3, A3.5 and A4. A dual resin cement
      (Rely X-ARC) was inserted into the prepared cavity. A mylar strip was positioned
      over the prepared cavity, and light curing was performed for 40 seconds following
      the protocols: controls-without insertion of the restoration at distances of 0.0,
      1.0, 2.0 and 4.0 mm. The remaining groups had the restorations positioned between
      the resin cement and light source during polymerization. The Vickers hardness
      test was performed on the cement layer with 50 g of load application for 30
      seconds, with 5 indentations for each sample. Two-way ANOVA (5 x 3) and Tukey
      test (alpha = 0.05) were used to compare the results. The chemical curing of the
      dual resin cement was not sufficient to compensate for the energy attenuation
      promoted by the interposition of A3.5 and A4 ceramic material with 4-mm of
      thickness. The thickness had a greater influence on the cement microhardness than
      the ceramic restoration shade.

PMID- 16802649
TI  - Individualized wedge.
AB  - The preparation of an individualized wedge in the gingival embrasure before
      cavity preparation using photo-cured resin permits rehabilitation of the
      interproximal space and the original contact point position. Because the
      individualized wedge completely fills the embrasure, the adaptation to the
      gingival and proximal walls of the molar to be restored is perfect, avoiding any
      overextension of obturation material during insertion. Furthermore, the original
      position of the contact point is preserved.

PMID- 16802650
TI  - Light protection of fiber-reinforced strip using aluminum foil for the direct
      splinting technique.
AB  - The critical point of the clinical procedure of direct splinting is the placement
      of the fiber-reinforced strip, which has to be well adapted to tooth surfaces.
      This article describes the use of aluminum foil to cover and protect the fiber
      reinforced strip from light polymerization during the direct splinting technique.
      The advantage of using aluminum foil is to prevent premature curing of the fiber
      reinforced strip, which would necessitate repetition of the procedure. With this
      technique, the strip is gradually exposed and adapted to the lingual/palatal
      surfaces of the teeth and light cured, allowing for ample working time.

PMID- 16802652
TI  - To belong or not to belong.

PMID- 16802651
TI  - The long and winding road.

PMID- 16802653
TI  - Pressure sores and end of life considerations.

PMID- 16802654
TI  - New rules for radiologist assistants?

PMID- 16802655
TI  - MedTenn 2006: health insurance, expert witness, MLR dominate debate.

PMID- 16802656
TI  - Cancer coalition: "taking it to the streets".

PMID- 16802657
TI  - How healthy is organized medicine? A "checkup" on medical societies.

PMID- 16802658
TI  - Fundamental technical error.

PMID- 16802659
TI  - Dealing with malpractice stress, Part I.

PMID- 16802660
TI  - Anti-trust implications of independent practice or associations.

PMID- 16802661
TI  - New pilot program helps physicians monitor chronically ill patients between
      office visits.

PMID- 16802662
TI  - Surgeon-performed ultrasound in the diagnosis and management of pericardial
      tamponade in a 20-month-old blunt injured toddler.
AB  - The contents of the thorax, although less frequently injured in children than in
      adults, remain a source of substantial potential morbidity and mortality in
      traumatized children. Disparate problems such as rib fractures, lung injury,
      hemothorax, pneumothorax, mediastinal injuries and others may present in
      isolation or in combination with one another. Knowledge of the manner in which
      pediatric anatomy, physiology and injury patterns change with age may expedite
      evaluating pediatric chest after trauma. We present the case of a 20-month-old
      toddler with blunt myocardial injury and pericardial tamponade diagnosed with
      surgeon-performed Focused Abdominal Sonography for Trauma (FAST).

PMID- 16802663
TI  - Readability of Notices of Privacy Practices in Tennessee.

PMID- 16802664
TI  - The ADA and alcohol use disorders among physicians.

PMID- 16802665
TI  - Medical topography.

PMID- 16802666
TI  - The future of voluntary governance.
AB  - Opinions about whether or not trustees should be paid waver between the belief
      that the need for sharpened board expertise demands compensation to the
      philosophy that payment is an affront to trustees' altruism.

PMID- 16802667
TI  - Gimme five. Community hospitals collaborate in the midst of competition.
AB  - Community Care 5, a collaboration among five Ohio hospitals, proves that hospital
      leaders can come together for the common good and still maintain a healthy
      competition with one another.

PMID- 16802668
TI  - Back to basics 2. The role of the board in the IT discussion.

PMID- 16802669
TI  - Attention investors. The Q-revolution is spreading.
AB  - Although there is no hard proof that higher quality and better patient safety
      translate into a better bottom line, the benefits are still clear and powerful.

PMID- 16802670
TI  - Assessing the IT health of your hospital.

PMID- 16802671
TI  - James Ho: his heart is in San Francisco.

PMID- 16802672
TI  - The board's role with impaired physicians.

PMID- 16802673
TI  - Governance. Vetting for succession.

PMID- 16802674
TI  - Decision making: in mothers' own voices.

PMID- 16802675
TI  - The Neonatal Bowel Output Study: indicators of adequate breast milk intake in
      neonates.
AB  - PURPOSE: This study describes the bowel habits of neonates who were exclusively
      breastfed during the first 14 days following birth to determine whether bowel
      output (frequency and character) could be used as a proxy measure for adequate
      breast milk intake. STUDY DESIGN: A prospective, descriptive study was conducted.
      During the 14-day study period, mothers kept a log of their infants' daily naked
      weight, number of feedings, number of daily bowel movements, and color of all
      bowel movements. PARTICIPANTS: One hundred thirty-one participants were enrolled
      in the study; 73 participants completed the study. FINDINGS: Findings indicate
      that more bowel movements per day during the first 5 days following birth were
      significantly associated with less initial weight loss, earlier transition to
      yellow bowel movements, earlier return to birth weight, and heavier weight at 14
      days. CONCLUSIONS: These findings suggest that scant bowel output during the
      first 5 days following birth, or delayed transition of bowel movements to yellow,
      warrant weighing the infant in a health care professional's office.

PMID- 16802676
TI  - Jaundice in the full-term newborn.
AB  - Jaundice is a common problem affecting over half of all full-term and most
      preterm infants. Jaundice describes the yellow orange hue of the skin caused by
      excessive circulating levels of bilirubin that accumulate in the skin. In most
      healthy full-term newborns, jaundice is noticed during the first week of life.
      Shortened hospital stays and inconsistent follow up, especially for first-time
      breastfeeding mothers, prompted the American Academy of Pediatrics (AAP) to
      update management guidelines. Health care providers need to be familiar with the
      diagnosis and management of jaundice to prevent brain, vision, and hearing
      damage. Treatment of choice for jaundice remains close observation and frequent
      feeding followed by phototherapy, and finally exchange transfusion for severe or
      refractory cases.

PMID- 16802677
TI  - Adolescent postpartum care: what daughters want and what their mothers expect to
      provide.
AB  - A cross sectional survey design was used to measure mothers' (n=36) expected
      involvement in the care of their parenting adolescent daughters and grandchildren
      after postpartum discharge, and to measure adolescents' (n=36) expectations about
      their mothers' involvement in the care of themselves and their newborns.
      Adolescents were first-time low-risk English-speaking mothers 15-19 years of age
      with low-risk newborns. No difference was found between the amount of care
      mothers expected to give their daughters and the amount of care that daughters
      expected to receive from their mothers, z = -.500, p = .62. No difference was
      found between the amount of newborn care mothers expected to give their
      grandchildren and the amount of newborn care that daughters expected their
      mothers to provide, z = -1.000, p = .32. Involvement of mothers in the postpartum
      care of their daughters and grandchildren needs further study, but with
      precautions, nurses may consider including mothers in the maternal and newborn
      care of adolescents.

PMID- 16802678
TI  - Observation of behavior in sedated, mechanically ventilated children.
AB  - This observation study examined the behaviors of 20 sedated, mechanically
      ventilated children, ages 1 month to 14 years. Observations were made using the
      Comfort Scale at the beginning and end of the two-hour observation period and of
      body and facial movements, behavior state, and environmental activity occurring
      during the 2-hour period. Mean Comfort scores at both measurement points were 16,
      below the target sedation level. In addition, while most children were in sleep
      states, they exhibited many body movements, particularly of the upper
      extremities. Body movements were related to behavior state but not to Comfort
      scores. Environmental activity was not significantly related to child activity,
      behavior state, or Comfort scores. Sedation scales in children may be best used
      in conjunction with behavior observations although further research is needed to
      determine the predictive capabilities of either scales or behavior on actual
      ventilation outcomes.

PMID- 16802679
TI  - Care and management of the child with shunted hydrocephalus.
AB  - This article reviews the physiology of cerebrospinal fluid formation and flow,
      the causes of hydrocephalus in the pediatric patient, symptoms of increased
      intracranial pressure, recent advances in shunt technology, the medical and
      surgical management of hydrocephalus, and potential complications of ventricular
      shunting devices. Nursing care in the post-operative period and for the child
      with shunt malfunction is discussed, as well as the long-term management needs
      and anticipatory guidance issues as related to a child with a ventricular
      shunting device. A case study of an infant with hydrocephalus illustrates key
      concepts.

PMID- 16802680
TI  - Nursing the child who is alone in the hospital.
AB  - Because of advances in medical technology, many critically burned children now
      survive horrendous injures that they would not have survived less than 10 years
      ago. Pediatric burn intensive care unit (BICU) nurses provide around the clock
      care, giving them greater contact with the children than any other health care
      professional. Often the children are alone in the hospital because their parents
      or care providers were injured or killed in the accident, live in another
      country, or are at home caring for other family members. Thematic analysis of
      data obtained during 112 hours of interviews and 134 hours of observation with 16
      BICU nurses resulted in the identification of four categories of nurses'
      practices that helped the holistic healing of children who were alone on the BICU
      of a hospital in the southwestern United States: (a) being a parent-minded nurse;
      (b) sustaining human connections; (c) receiving the patient as a child; and (d)
      renewing the spirit of the child.

PMID- 16802681
TI  - Mother of ex-premature infant instructed to measure head circumference daily.

PMID- 16802682
TI  - In their own voices: families discuss end-of-life decision making--part 2.
AB  - This two part series of articles presents poignant narratives based on interviews
      done with two mothers who suffered the worst pain imaginable--the pain of losing
      a child. Each woman describes an insensitive health care system with providers
      unaware of parental views and needs when confronted with difficult decisions
      during their children's illnesses and subsequent deaths. Each woman also hoped
      that telling her story might help nurses and other health care providers better
      understand how to help. Part 1 of the series is the story of a professional,
      highly educated mother who experienced periods of extreme distress while she
      tried to give her premature daughter an identity and meaningful life in the
      neonatal intensive care unit and the difficulties faced when she was transferred
      to another unit as she became more ill Part 2 of the series is the story of a
      highly devoted working mother who tried to understand the information that was
      rarely offered to her as she lived through the extreme surgical and uncertain
      medical interventions given her toddler daughter with a fast-growing brain tumor.
      Both women faced hard decisions along their daughters' illness trajectories. Both
      hoped for support from their health care providers in being active in decision
      making. These narratives are in their own voices, from their own points of view.

PMID- 16802683
TI  - Effects on parents of an intervention to resolve infant behavioral sleep
      problems.
AB  - PURPOSE: Because behavioral sleep problems affect a large proportion of infants
      and can result in health issues for children and their parents, the study
      evaluated the effects of a sleep intervention for infants from 6 to 12 months
      old. METHOD: For this quasi-experimental one group pre-test and post-test design,
      39 eligible families were recruited through a newborn hotline. Seventy parents
      with healthy 6 to 12-month old infants completed the intervention. The
      intervention involved information about infant sleep and strategies for sleep
      problems in classes of up to 6 couples, chart completion, and bi-weekly telephone
      calls for 2 weeks. The primary outcome measures were parents' sleep quality,
      fatigue, cognitions about infant sleep, depression, marital harmony, and
      sleepiness. FINDINGS: Following the intervention, there was a significant
      improvement in parents' sleep quality, cognitions about infant sleep, fatigue,
      and depressed mood. CONCLUSIONS: The study findings demonstrated that providing
      parents with information and support to assist with infant behavioral sleep
      problems can improve parental psychological well being.

PMID- 16802684
TI  - A successful public health experiment: school nursing.

PMID- 16802685
TI  - A new role for pediatric nurses: teaching teen drug users how to sterilize their
      equipment for prevention of infectious disease; a course outline.
AB  - This article discusses a sensitive issue that is complex and provocative, and
      will undoubtedly stimulate a variety of opinions. What do you think? Post your
      comments about this topic on the Pediatric Nursing Web site and read what others
      have to say as well. Visit our homepage at www.pediatricnursing.net and click on
      "Discussion". The opinions and assertions contained herein are the private views
      of the contributors and do not necessarily reflect the views of Pediatric Nursing
      Journal or the publisher.

PMID- 16802686
TI  - Evidence-based practice: noninvasive blood pressure measurement in children.

PMID- 16802687
TI  - Dietary hydrogenated soybean oil affects lipid and vitamin E metabolism in rats.
AB  - Fatty acids containing stearic acid, which are found in hydrogenated fat, may
      have a detrimental effect on the cholesterol and triacylglycerol (TAG) content of
      plasma lipoproteins, and on the absorption of fatty acids and fat-soluble
      vitamins. The aim of our study was to examine the tissue concentration of lipids
      and vitamins A and E after feeding a hydrogenated soybean oil (HSO) diet to rats.
      Twenty male Sprague-Dawley rats were randomly divided into two groups, fed on
      coconut oil (control) and HSO, respectively in amounts corresponding to 15% of
      the total feed. Plasma total cholesterol, VLDL- and LDL-cholesterol, lipid
      peroxidation and daily excretion of the TAG and cholesterol in feces were higher
      in the HSO than in the control group. TAG values in plasma and liver, and HDL
      cholesterol levels in plasma were lower in the HSO than in the control group. The
      same was true for phospholipids in plasma and for saturated fatty acids, mono-
      and polyunsaturated fatty acids levels in the liver and vitamin E in plasma, LDL
      and adipose tissue. The results of this study provide new evidence concerning the
      effect of dietary hydrogenated fat on lipid, TAG and vitamin E status, which are
      important for maintenance of good health. Consumption of dietary HSO may be
      associated with cardiovascular disease.

PMID- 16802688
TI  - Heterologous expression of dehydroascorbate reductase from rice and its
      application to determination of dehydroascorbate concentrations.
AB  - We constructed an expression vector for rice dehydroascorbate reductase (DHAR)
      (EC 1.8.5.4) with a polyhistidine tag at the amino terminus and introduced the
      vector into several strains of Escherichia coli. On conventional induction
      treatment with isopropylthiol-beta-D-galactoside, E. coli harboring rice DHAR
      cDNA produced doublet polypeptides of about 27 kDa. Induction duration or growth
      temperature did not affect the ratio of these polypeptides. Only the larger
      polypeptide, corresponding to full-length recombinant DHAR, was produced in E.
      coli supplemented with tRNAs for several minor codons. Most of the enzymatic
      characteristics of the recombinant DHAR were similar to those of the native one,
      although the recombinant protein showed increased heat susceptibility. Using
      recombinant DHAR, we developed a method for simple and precise determination of
      dehydroascorbate concentrations in tissue extracts by spectrophotometry, and we
      successfully applied the method to several fruit juices and vegetables.

PMID- 16802689
TI  - Effects of dietary corn bran hemicellulose and neomycin on hepatic caspase-3
      activity and glycoprotein concentration in rats treated with or without D
      galactosamine.
AB  - The effects of dietary corn bran hemicellulose (CBH) and neomycin (Neo) on
      hepatic caspase-3 activity and glycoprotein concentration were investigated to
      explore the possible mechanism of the alleviative action of dietary CBH and Neo
      on the development of D-galactosamine (GalN)-hepatitis. Rats were fed a diet
      containing 5% CBH with or without neomycin (Neo) for 7 or 14 d. On the last day
      of feeding, the rats were treated with GalN (400 mg/kg body weight, i.p.), and
      their plasma transaminase activities, hepatic glycoprotein concentrations and
      hepatic caspase-3 activities were determined 6 or 24 h later. Although the
      elevations of plasma transaminase activities were suppressed by CBH or Neo 24 h
      after GalN-treatment, the activities were not affected by CBH or Neo at an early
      stage (6 h) of GalN action. At 6 h, hepatic caspase-3 activity was elevated by
      CBH diet alone as high as that of the GalN-injected control-diet group, and the
      activity was not elevated further by GalN. At the same time, both GalN-treatment
      and CBH feeding reduced the hepatic glycoprotein (Mw. 64,000-74,000)
      concentration, but Neo did not affect the caspase activity or the glycoprotein
      concentration. These results suggest that dietary CBH elevates hepatic caspase-3
      activity and reduces hepatic glycoprotein concentration, and may imply that CBH
      would suppress GalN-hepatitis not at the early- or middle-step of apoptosis but
      at the late-step of apoptosis or necrosis, although the relation between these
      phenomena and the alleviative effects of CBH and Neo on GalN-induced hepatitis is
      yet to be clarified.

PMID- 16802690
TI  - Sucrase-isomaltase gene expression is inhibited by mutant hepatocyte nuclear
      factor (HNF)-1alpha and mutant HNF-1beta in Caco-2 cells.
AB  - Hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta are concerned in sucrase
      isomaltase (SI) gene expression, and directly bind two sites (SIF2, SIF3) of the
      promoter of the SI gene. However, it is not completely clear that HNF-1alpha and
      HNF-1beta play a role in regulation of SI gene expression. To clarify mechanisms
      of SI gene expression regulated by HNF-1alpha and HNF-1beta, we established four
      stable cell lines based on enterocyte-like cell line Caco-2, in which wild HNF
      1alpha or wild HNF-1beta, or else mutant HNF-1alphaT539fsdelC or mutant HNF
      1betaR177X was overexpressed. In the HNF-1alphaT539fsdelC cells and HNF
      1betaR177X cells, but not in the wild HNF-1alpha cells and wild HNF-1beta cells,
      SI gene expression and enzyme activity were significantly diminished compared
      with that in Caco-2 cells. Moreover, to clarify whether or not stable cell
      differentiation was influenced by overexpression of these transgenes, alkaline
      phosphatase (ALP) gene expression and enzyme activity were measured. There were
      no changes in ALP gene expression or enzyme activity in these cells. These
      observations suggest that mutant HNF-1alphaT539fsdelC and mutant HNF-1betaR177X
      inhibits SI gene at the transcriptional level, resulting in decreased SI enzyme
      activity in Caco-2 cells. We propose that both HNF-1alpha and HNF-1beta would
      contribute to constitutive expression of the SI gene in the differentiated state
      in Caco-2 cells.

PMID- 16802691
TI  - Modulation of oral tolerance to ovalbumin by dietary protein in mice.
AB  - This study sought to determine whether oral tolerance to ovalbumin (OVA),
      responsible for food allergy, is affected by different amounts of protein intake.
      For this, 6-wk-old BALB/c mice were fed with low protein (5%, LP), normal protein
      (20%, NP) and high protein (40%, HP) diets, orally given either OVA (OVA-fed) or
      water (Water-fed) for 4 d, and then immunized intraperitoneally twice at a 3-wk
      interval with alum-precipitated OVA. After the last immunization, sera were
      collected to measure total and OVA-specific IgE by enzyme assay (ELISA).
      Splenocytes were cultured and stimulated with concanavalin A (Con A),
      lipopolysaccharide (LPS) or OVA and assayed for 3H-thymidine incorporation. The
      culture supernatants from their splenocytes stimulated with OVA were analyzed for
      interleukin (IL)-4, interferon (IFN)-gamma, and IL-12. Total IgE was
      significantly higher in OVA-fed HP groups as compared to NP and LP groups
      (p<0.05). The highest and the lowest OVA-specific IgE were observed in HP and LP
      diet groups, respectively (p<0.05). OVA-fed mice receiving the LP diet
      demonstrated significantly lower IL-4 as compared to the other two groups
      (p<0.05), while IFN-gamma was significantly higher in the LP compared to the HP
      group (p<0.05). Levels of IL-12 did not differ among the OVA-fed groups.
      Splenocytes of OVA-fed mice kept on the LP and HP diet showed significant
      impairment of proliferation to OVA as compared to the NP group (p<0.01).
      Proliferation against Con A was impaired in the LP group compared to the NP group
      (p<0.05) but not in Water-fed groups. However, it was higher against LPS in the
      HP than the LP group (p<0.05) both in Water-fed and OVA-fed animals. All these
      findings indicate that established oral tolerance to OVA is clearly affected by
      the amount of protein diet. They support the suggestion that dietary protein
      plays an important role(s) in IgE-mediated food allergies.

PMID- 16802692
TI  - Moisture and mineral content of human feces--high fecal moisture is associated
      with increased sodium and decreased potassium content--.
AB  - BACKGROUND: The origin of moisture in diarrhea feces is unknown but may represent
      the unabsorbed part of intestinal contents or alternatively, body fluid excreted
      into the digestive canal. If the latter mechanism contributes to moisture in the
      feces, active transport of water (H2O) associated with ion exchange channels may
      be involved. OBJECTIVE: To investigate this possibility we measured the content
      of moisture and minerals (sodium [Na], potassium [K], calcium [Ca], magnesium
      [Mg], phosphorus [P], zinc [Zn], iron [Fe], copper [Cu] and manganese [Mn]) in
      feces collected during a 12-d metabolic study on 11 young Japanese female
      students. DESIGN: The study was carried out as part of a human mineral balance
      study. The same quantity of food was supplied to each of the subjects throughout
      the study without consideration of body weight. Fecal specimens were collected
      throughout the study and were separated into those originating from the diet
      during the balance period based on the appearance of the ingested colored marker
      in the feces. RESULTS: The moisture content of the feces ranged between 53 and
      92%. Na content in the feces was low and stable when the moisture content was
      below 80%, whereas it increased up to serum levels when the moisture content
      increased above 80%. On the other hand, K content increased when compared to dry
      matter base. However, when comparing concentration/g moisture, K content
      increased when moisture was below 70%, but decreased when this rose above 70%.

PMID- 16802693
TI  - Dietary 5-campestenone (campest-5-en-3-one) enhances fatty acid oxidation in
      perfused rat liver.
AB  - The effect of dietary 5-campestenone (campest-5-en-3-one), a chemical
      modification product of a naturally-occurring plant sterol, campesterol, on lipid
      metabolism was examined using a rat liver perfusion system. Male Sprague-Dawley
      rats weighing about 140 g were fed a diet supplemented with or without 0.2% 5
      campestenone for 14 d. 5-Campestenone feeding resulted in a marked reduction in
      the concentrations of serum lipids, such as triacylglycerol (TG), cholesterol,
      phospholipid, and free fatty acid, without influencing food intake or growth.
      Then, isolated livers from both groups were perfused for 4 h in the presence of
      an exogenous linoelaidic acid substrate. Dietary 5-campestenone markedly elevated
      hepatic ketone body production, while cumulative secretions of TG, cholesterol,
      and phospholipid by the livers of rats fed 5-campestenone were all significantly
      lowered as compared to those fed without the compound: the extent of the
      reduction was more prominent in the secretion of TG than other lipid components.
      In addition, the reduction of TG secretion was concomitantly accompanied by the
      reduced incorporation of both exogenous and endogenous fatty acids into this
      lipid molecule. These results suggest that dietary 5-campestenone exerts its
      hypotriglyceridemic effect, at least, in part through an enhanced metabolism of
      endogenous and exogenous fatty acids to oxidation at the expense of
      esterification in rat liver.

PMID- 16802694
TI  - Retrograded tapioca starch prevents ovarian hormone deficiency-induced
      hypercholesterolemia.
AB  - The purpose of this study was to examine whether retrograded tapioca starch (RS3
      tapioca) prevents ovarian hormone deficiency-induced hypercholesterolemia. Six
      month-old Wistar female rats were subjected to sham-operation or ovariectomy, and
      fed a cholesterol-free purified diet with or without RS3-tapioca (150 g/kg diet)
      instead of digestible cornstarch for 28 d. Body weight gain and food intake
      increased in ovariectomized rats (OVX-rats). Plasma total cholesterol
      concentration was lowered by RS3-tapioca in OVX rats, but not in sham-operated
      rats. Liver lipids increased in OVX-rats, but liver cholesterol concentration was
      not affected by ovariectomy and RS3-tapioca. CYP7A1 activity, small intestinal
      and cecal bile acid content, and fecal bile acid excretion were increased by RS3
      tapioca. The ratio of cholic acid groups to chenodeoxycholic acid groups in the
      bile acid of the small intestine was increased by RS3-tapioca. Thus, the
      preventive effect of RS3-tapioca on the ovarian hormone deficiency-associated
      increase in plasma cholesterol concentration appears to be mediated by
      accelerated fecal excretion of bile acid and an increase in the intestinal pool
      of bile acid.

PMID- 16802695
TI  - Comparison of metabolic fates of nicotinamide, NAD+ and NADH administered orally
      and intraperitoneally; characterization of oral NADH.
AB  - Since NADH has been implicated in medication for some symptoms and as a possible
      supplement for health, we characterized the metabolic fate of NADH orally given
      to mice by comparing with those of nicotinamide (Nam), NAD+ and NADH
      intraperitoneally or orally administered. Mice were individually housed in
      metabolic cages, and divided into two sets of four groups. Within each set, one
      group was intraperitoneally or orally administered saline and the other three
      groups received intraperitoneal or oral administration of a pharmacological dose
      of Nam, NAD+ or NADH (5 micromol/mouse). Twenty-four hour urine samples for the
      day before and days 1 to 4 after administration were collected and analyzed for
      Nam and its metabolites. When mice were administered saline alone, urinary
      excretion of Nam and its metabolites, such as nicotinamide N-oxide (Nam N-oxide),
      N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py), and N1
      methyl-4-pyridone-3-carboxamide (4-Py), was unchanged from day 0 to day 4.
      Intraperitoneal injection of Nam, NAD+ and NADH produced significant increases in
      urinary excretion of Nam and its metabolites. Similar results were obtained when
      Nam and NAD+ were given orally. On the other hand, oral administration of NADH
      did not bring about an increase in urinary excretion of Nam and its metabolites,
      suggesting that NADH in digestive organs has been decomposed to a compound(s)
      that cannot yield Nam. In fact, incubation of NADH at acidic pH to mimic the
      stomach resulted in rapid conversion of NADH to an unknown compound. Better
      understanding of the fate of oral NADH is needed for its therapeutic and
      supplemental use.

PMID- 16802696
TI  - Inhibition of alpha-glucosidase and alpha-amylase by flavonoids.
AB  - The inhibitory activity of six groups of flavonoids against yeast and rat small
      intestinal alpha-glucosidases and porcine pancreatic alpha-amylase was compared,
      and chemical structures of flavonoids responsible for the inhibitory activity
      were evaluated. Yeast alpha-glucosidase was potently inhibited by the
      anthocyanidin, isoflavone and flavonol groups with the IC50 values less than 15
      microM. The following structures enhanced the inhibitory activity: the
      unsaturated C ring, 3-OH, 4-CO, the linkage of the B ring at the 3 position, and
      the hydroxyl substitution on the B ring. Rat small intestinal alpha-glucosidase
      was weakly inhibited by many flavonoids, and slightly by the anthocyanidin and
      isoflavone groups. 3-OH and the hydroxyl substitution on the B ring increased the
      inhibitory activity. In porcine pancreatic alpha-amylase, luteolin, myricetin and
      quercetin were potent inhibitors with the IC50 values less than 500 microM. The
      2,3-double bond, 5-OH, the linkage of the B ring at the 3 position, and the
      hydroxyl substitution on the B ring enhanced the inhibitory activity, while 3-OH
      reduced it.

PMID- 16802697
TI  - Accuracy of body fat assessment by bioelectrical impedance in Japanese middle
      aged and older people.
AB  - Bioelectrical impedance analysis (BIA) is commonly used to measure the percentage
      of body fat (%BF), but its accuracy is controversial. In addition, the equations
      are specific to the group for which they were established. As far as we know,
      there is no study examining the accuracy of BIA in Japanese middle-aged and older
      people. We compared %BF assessed using BIA with that of dual-energy X-ray
      absorptiometry (DEXA) in 102 female and 51 male local residents aged 40 to 78 y.
      Simple correlation coefficients were 0.79 for females and 0.69 for males, which
      are statistically significant (p<0.001). However, BIA tended to overestimate %BF
      in the lower BF group and underestimate it in the BF higher group, and only 45.1%
      for female and 47.1% for male subjects were measured accurately, i.e., within 10%
      of the measurement by DEXA. This result suggests that this model of BIA is an
      alternative for estimating %BF in Japanese middle-aged and older people as well
      as when subjects are within a normal body fat range, but greater accuracy is
      needed for lean and overweight subjects.

PMID- 16802698
TI  - Antibacterial activity of citrus fruit juices against Vibrio species.
AB  - Lemon, lime and sudachi juices were tested for antibacterial activity against
      seven strains of Vibrio species. All juices were effective in inhibiting the
      growth of the Vibrio strains. Citric acid, the major organic acid in these
      juices, was found to be responsible for inhibiting the growth of Vibrio
      parahaemolyticus. Sauce prepared from sudachi juice showed a strong bactericidal
      activity against Vibrio parahaemolyticus, whereas the sauce adjusted to higher pH
      values had no bacterial activity. Diluted sudachi juice or citric acid solution
      also had antibacterial activity independently. These results suggest that citrus
      fruit juices are effective in preventing infection with Vibrio species.

PMID- 16802699
TI  - Folate determination in human milk.

PMID- 16802700
TI  - Preface: a brief review of N-acetylaspartate.

PMID- 16802701
TI  - A brief overview of N-acetylaspartate and N-acetylaspartylglutamate.

PMID- 16802702
TI  - Expression of N-acetylaspartate and N-acetylaspartylglutamate in the nervous
      system.

PMID- 16802703
TI  - N-acetylaspartate metabolism in neural cells.

PMID- 16802704
TI  - NAA synthesis and functional roles.

PMID- 16802705
TI  - Identity of the high-affinity sodium/carboxylate cotransporter NaC3 as the N
      acetyl-L-aspartate transporter.

PMID- 16802706
TI  - Canavan disease: studies on the knockout mouse.
AB  - Canavan disease (CD) is an autosomal recessive disorder, characterized by spongy
      degeneration of the brain. Patients with CD have aspartoacylase (ASPA)
      deficiency, which results accumulation of N-acetylaspartic acid (NAA) in the
      brain and elevated excretion of urinary NAA. Clinically, patients with CD have
      macrocephaly, mental retardation and hypotonia. A knockout mouse for CD which was
      engineered, also has ASPA deficiency and elevated NAA. Molecular studies of the
      mouse brain showed abnormal expression of multiple genes in addition to ASPA
      deficiency. Adenoassociated virus mediated gene transfer and stem cell therapy in
      the knockout mouse are the latest attempts to alter pathophysiology in the CD
      mouse.

PMID- 16802707
TI  - Functions of N-acetylaspartate and N-acetylaspartylglutamate in brain: evidence
      of a role in maintenance of higher brain integrative activities of information
      processing and cognition.

PMID- 16802708
TI  - Control of brain volume during hypoosmolality and hyperosmolality.
AB  - Multiple studies over several decades have provided evidence that both
      electrolytes and organic osmolytes play crucial roles in regulating brain volume,
      both during increases as well as during decreases in extracellular fluid
      osmolality. In both situations, rapidly, and however, changes in brain
      electrolyte contents appear to occur more represent the first line of defense of
      brain volume during acute perturbations of body fluid tonicity, while organic
      osmolytes allow adaptation to more chronic perturbations. For both
      hyperosmolality and hypoosmolality, the rate of development of the disorder is an
      important determinant of neurological morbidity and mortality, since sufficiently
      rapid changes in tonicity can exceed the brain's capacity to regulate its volume
      leading to more severe degrees of brain edema or dehydration. Recovery from both
      hyper- and hypoosmolality requires reversal of the adaptive processes that
      enabled regulation of brain volume in response to the initial insult. However,
      adaptation and recovery are not symmetrical processes. Marked differences occur
      in the speed with which the brain is able to lose or to reaccumulate different
      types of solutes after recovery from chronic disturbances of body fluid tonicity.
      In general, accumulation, or reaccumulation, of organic solutes by brain tissue
      is a much slower process than volume regulatory losses of such solutes. As with
      the adaptation process, the rate of recovery is an important determinant of
      subsequent morbidity and mortality, since rapid corrections of osmolality can
      also exceed the capacity of the brain to readjust its solute content, and
      consequently its volume, back to normal levels. Whether or not transient excesses
      or deficiencies of either electrolytes or specific organic osmolytes in brain
      intracellular or extracellular fluid contribute to functional disturbances
      independently of changes in brain volume is an intriguing question that has not
      been sufficiently evaluated. Also remaining to be answered are questions
      regarding other physiological, pathophysiological, and pharmacological factors
      that either impair or enhance volume regulatory processes, and thereby modify the
      neurological manifestations accompanying disorders of body fluid osmolality in
      humans. Finally, a complete understanding of the cellular mechanisms underlying
      adaptation to and deadaptation from acute and chronic perturbations of body
      osmolality will be essential to design the most enlightened, and therefore
      appropriate, treatments for these disorders.

PMID- 16802709
TI  - Physiological role of N-acetylaspartate: contribution to myelinogenesis.

PMID- 16802710
TI  - Defective myelin lipid synthesis as a pathogenic mechanism of Canavan disease.

PMID- 16802711
TI  - Mutation analysis of the aspartoacylase gene in non-Jewish patients with Canavan
      disease.

PMID- 16802712
TI  - Does ASPA gene mutation in Canavan disease alter oligodendrocyte development? A
      tissue culture study of ASPA KO mice brain.

PMID- 16802713
TI  - Quantitation of NAA in the brain by magnetic resonance spectroscopy.

PMID- 16802714
TI  - N-acetyl-L-aspartate in multiple sclerosis.

PMID- 16802715
TI  - NAA and higher cognitive function in humans.

PMID- 16802716
TI  - In vivo NMR measures of NAA and the neurobiology of schizophrenia.

PMID- 16802718
TI  - Regulation of NAA-synthesis in the human brain in vivo: Canavan's disease,
      Alzheimer's disease and schizophrenia.

PMID- 16802717
TI  - N-acetylaspartate as a marker of neuronal injury in neurodegenerative disease.

PMID- 16802719
TI  - Magnetic resonance spectroscopy for monitoring neuronal integrity in amyotrophic
      lateral sclerosis.

PMID- 16802720
TI  - Hypoacetylaspartia: clinical and biochemical follow-up of a patient.

PMID- 16802721
TI  - Cellular localization of NAAG.

PMID- 16802722
TI  - Synthesis of N-acetylaspartyl-glutamate (NAAG) and N-acetylaspartate (NAA) in
      axons and glia of the crayfish medial giant nerve fiber.

PMID- 16802723
TI  - NAAG as a neurotransmitter.

PMID- 16802724
TI  - Glutamate carboxypeptidase II (NAALADase) inhibition as a novel therapeutic
      strategy.
AB  - GCP II inhibition decreases extracellular excitotoxic glutamate and increases
      extracellular NAAG, both of which provide neuroprotection. We have demonstrated
      with our potent and selective GCP II inhibitors efficacy in models of stroke, ALS
      and neuropathic pain. GCP II inhibition may have significant potential benefits
      over existing glutamate-based neuroprotection strategies. The upstream mechanism
      seems selective for excitotoxic induced glutamate release, as GCP II inhibitors
      in normal animals induced no change in basal glutamate. This suggestion has
      recently been corroborated by Lieberman and coworkers24 who found that both NAAG
      release and increase in GCP II activity appear to be induced by electrical
      stimulation in crayfish nerve fibers and that subsequent NAAG hydrolysis to
      glutamate contributes, at least in part, to subsequent NMDA receptor activation.
      Interestingly, even at relatively high doses of compounds, GCP II inhibition did
      not appear to be associated with learning/memory deficits in animals.
      Additionally, quantitative neurophysiological testing data and visual analog
      scales for 'psychedelic effects' in Phase I single dose and repeat dose studies
      showed GCP II inhibition to be safe and well tolerated by both healthy volunteers
      and diabetic patients. GCP II inhibition may represent a novel glutamate
      regulating strategy devoid of the side effects that have hampered the development
      of postsynaptic glutamate receptor antagonists.

PMID- 16802725
TI  - N-acetylaspartylglutamate (NAAG) in spinal cord injury and disease.

PMID- 16802726
TI  - N-acetylaspartylglutamate (NAAG) in Pelizaeus-Merzbacher disease.

PMID- 16802727
TI  - [Development and evaluation of a prosthetic valved conduit dilated by
      percutaneous approach: experimental study in the lamb].
AB  - This study was undertaken to develop a dilated valved conduit for reconstruction
      of the right ventricular outflow tract in the animal. The conduits were made by
      sewing a valved tube (Medtronic Inc) inside a vascular stent (Numed Inc). After
      preparation, they were inserted surgically in five lambs. The conduits were then
      dilated 6 weeks and 3 months after their implantation. Before sacrificing the
      animals at 3 months, a 22 mm valved stent was implanted percutaneously inside the
      surgical conduits. One animal died suddenly due to kinking of the conduit.
      Balloon dilatation was performed in the surviving animals. The first dilatation
      only had a modest impact on valvular function but it was much aggravated after
      the second dilatation. A valved stent was successfully inserted percutaneously.
      At sacrifice, all the conduits were completely engulfed in an intense fibrosis.
      In conclusion, a valved biological conduit for reconstruction of the right
      ventricular ejection tract has been developed and can be dilated sequentially to
      follow growth. The new product could have an important role to play in the
      management of congenital malformations involving the right ventricular outflow
      tract.

PMID- 16802728
TI  - [Percutaneous angioplasty of native coarctation of the aorta. Results in children
      and young adults].
AB  - The authors report the experience of one centre in the treatment of native
      coarctation of the aorta by percutaneous angioplasty. Between 1999 and August
      2005, 22 patients (7 girls, 15 boys) underwent dilatation of their coarctation by
      a balloon catheter at an average age of 11.8 +/- 5 years and body weight of 44 +/
      21 kg. In 20 patients, balloon angioplasty alone was performed and, in the other
      two, the angioplasty was associated with the insertion of a covered CP stent. The
      dilatation was performed with a balloon/coarctation ratio of 2.18 +/- 0.6 (1.7 to
      3.5) and a balloon/isthmus ratio of 1.0 +/- 0.23 (0.7 to 1.87). After the
      procedure, ascending aortic pressure decreased from 134.7 +/- 23.4 mmHg to 125 +/
      22.7 mmHg (p= 0.0003); descending aortic pressure increased from 93.4 +/- 14.9
      mmHg to 104.8 +/- 21.7 mmHg (p= 0.003); transisthmic pressure gradient decreased
      from 41.7 +/- 14.1 mmHg to 19.8 +/- 9.5 mmHg (p< 0.0001) and the diameter of the
      coarctation increased from 5.9 +/- 2.6 mm to 9.3 +/- 2.6mm (p= 0.0015). The two
      patients treated by covered CP stents had excellent immediate results without
      significant residual gradients. After dilatation (sometimes repeated, N= 13), a
      gradient > 20 mmHg persisted in ten patients (36% of cases) but no predictive
      factor was found on statistical analysis. There were no cases of acute aneurysm.
      In one patient, the femoral pulse decreased but returned to normal with heparin
      therapy. No patient required emergency surgical treatment after the angioplasty.
      During the clinical follow-up, echocardiography and MRI showed no signs of
      aneurysm and one patient had mild irregularity of the isthmic region. Three
      patients underwent surgery by resection suture for persistent coarctation (one
      combined with a Ross procedure); another patient was treated by a CP stent. In
      conclusion, percutaneous angioplasty of native coarctation of the aorta gives
      satisfactory results with few complications in bigger children and young adults.
      The results can be improved by using a slightly higher balloon/coarctation ratio.

PMID- 16802729
TI  - [Use of covered stents to occlude extracardiac Fontan fenestration].
AB  - INTRODUCTION: A fenestration is usually surgically created to improve the post
      operative course of patients undergoing total cavopulmonary connection. It,
      however, has a potentially deleterious effect on the long-term period. Closure of
      these fenestrations is usually performed by interventional catheterization. No
      device has been specially designed and closure of extracardiac fenestration, in
      particular, can be challenging. We report our experience in occlusion of such
      fenestrations using covered stents (Numed Inc). METHODS: From July 2005 to
      October 2005, we attempted to occlude extracardiac Fontan fenestration using CP
      covered stents in 4 consecutive patients. RESULTS: All patients had a successful
      occlusion of the fenestration. The procedure was performed from femoral or
      jugular vein respectively in three and one patient. Mean central venous pressure
      did not increase significantly (from 11.25 to 12.75 mmHg) whereas mean oxygen
      saturation increased significantly from 92% to 99% (p=0.0047). Abolition of shunt
      was obtained immediately after insertion of the covered stent in all patients. No
      early complications were observed. All patients were ambulatory the day after the
      procedure. CONCLUSION: The insertion of a covered stent inside the extracardiac
      Fontan conduit allowed the exclusion of the fenestration in all patients without
      the need of crossing the fenestration and with no early mortality or morbidity.
      Long-term follow-up are needed before considering the use of such device as the
      device of choice in that application.

PMID- 16802730
TI  - [Large atrial septal defects in adults: results of attempted systematic
      percutaneous closure].
AB  - Percutaneous closure of ostium secundum atrial septal defects became routine
      practice from 1998 but remained limited by the size of their diameter at balloon
      calibration. In March 2004, after an experience of 551 patients, the maximum
      admissible diameter (40 mm), the biggest size available of the Amplatzer
      prosthesis, could often be exceeded. The essential anatomical condition was the
      presence of a circumferential edge--even minimal--except adjacent to the aorta
      where its absence was not a problem. From 31/03/04 to 31/12/05, 17 patients, 17
      to 58 years of age, were included and underwent attempted percutaneous closure by
      the usual protocol. The insertion of the prosthesis was difficult in every case.
      It required the use of several techniques to orientate the prosthesis in a
      satisfactory plane without risking tearing part of the residual atrial septum.
      The attempt was successful in 16 of the 17 patients. The one failure occurred in
      a patient with complete absence of a posterior edge. The postoperative course was
      uncomplicated without residual shunt or displacement of the occluder in the
      follow-up studies. The authors conclude that very big atrial septal defects with
      diameters of over 40 mm may be closed percutaneously with the Amplatzer device
      with a reasonable chance of success. These attempts do not expose the patient to
      any particular risk and the results, in successful attempts, are comparable to
      those observed in smaller atrial septal defects.

PMID- 16802731
TI  - [Implantable cardioverter defibrillators in pediatric patients: results in a
      series of 33 cases].
AB  - Implantable defibrillator is the recognized treatment of sudden cardiac death.
      Miniaturization of the devices allows implantation in children. METHODS: This
      multicentric retrospective study analyzed data of 33 children aged 18 years and
      less who were implanted from 1990 to 2005. RESULTS: Age of patients are 10 to 18
      years, 20 patients were implanted after a resuscitation of sudden death, 10 after
      a syncope, 2 after a ventricular tachycardia and 1 in a prophylactic way.
      Tachycardias on primary electrical disease are most frequent (46%). Hypertrophic
      cardiomyopathy accounts for 22%, DAVD for 14%, congenital cardiopathies for 12%.
      Seventeen patients received appropriate shocks and 14 patients had inappropriate
      shocks. There were two unexplained deaths. Five leads fractures and two device
      infections were noted. CONCLUSION: Implantable defibrillator is an effective
      treatment for children high-risk of sudden death. Occurrence of inappropriate
      shocks due to sinusal tachycardia, infections and leads fractures are frequent.

PMID- 16802732
TI  - [The role of aortic morphology in the occurrence of hypertension in patients
      undergoing surgery for coarctation of the aorta before the age of 1 year].
AB  - OBJECTIVE: Hypertension on effort can be observed following surgical treatment of
      coarctation of the aorta even if the operation has been performed early and has
      been judged to be satisfactory. The pathophysiology of this hypertension has not
      been completely elucidated. The aim of our study was to look for a residual
      morphological anomaly of the aortic arch which might be responsible. METHODS:
      This was a retrospective study of patients aged over 10 years who had undergone
      surgery for coarctation of the aorta before the age of 1 year, consecutively
      between 1979 and 1993, and free from re-coarctation clinically or with Doppler.
      All of them had a blood pressure effort test on a cycling machine,
      echocardiography and an MRI of the thoracic aorta. RESULTS: 61 patients were
      included. Their median age was 15 years, 59% were male, 15% were hypertensive at
      rest and 56% on effort. With univariate analysis, only the average blood pressure
      (p=0.03) and the resting pulse pressure (p=0.001) were associated with
      hypertension on effort. With multivariate analysis the only factors that
      correlated independently with maximum arterial pressure on effort were the height
      of the patient (p=0.02) and the pulse pressure (p<0.0001). The surgical technique
      and the age at intervention were not associated with hypertension on effort
      (p=0.96 and 0.69 respectively). The diameter of the horizontal aorta and the
      aorta at the site of repair, measured on MRI, added to the diameter of the
      descending aorta at the diaphragm were not lower in patients with hypertension on
      effort (p=0.77 and 0.38). There were proportionally more Roman type aortic arches
      than Gothic types in patients with hypertension on effort, but this difference
      was not significant (p=0.18). CONCLUSION: In our study, the patients with
      hypertension on effort following correction of coarctation of the aorta did not
      display any residual obstruction at the level of the aortic cross on MRI.
      However, they had a resting pulse pressure that was significantly higher than the
      non hypertensive patients, reflecting an increase in the aortic wall rigidity.

PMID- 16802733
TI  - [Medium and long-term results of anatomical correction of transposition of the
      great arteries in Marseille].
AB  - The object of this study was to evaluate the results of anatomical correction of
      transposition of the great arteries (TGA) in an inter-regional centre. The
      characteristics of 220 patients operated between 1985 and 2002 were analysed.
      Prenatal diagnosis of TGA was made in 38 patients (17%) including 36 of the 109
      patients operated since 1995 (33%) and leading to earlier atrial septostomy in
      this situation (p= 0.046). Since 1995, the global early mortality of 12.3% has
      been significantly reduced to 5.5% (N= 6) including 4.4% (3/68 cases) of simple
      TGA (p= 0.002). In multivariate analysis, the only independent risk factor for
      early mortality was the occurrence of a major per-operative complication (p<
      0.0001). The average follow-up was 4.8 +/- 4.5 years with an 86% survival at 5,
      10 and 15 years and 97% survival at 5 years for patients operated after 1995.
      There were 22 reoperations including 14 on the right ventricular outflow tract.
      The non-reoperation rate at 10 years was 80% for simple TGA versus 70% in complex
      TGA (p= 0.0001). Survivors are asymptomatic with a normal ECG and normal LV
      function on echocardiography. Five patients have significant pulmonary stenosis
      and 4 have mild aortic regurgitation. The exercise stress tests performed between
      the ages of 7 and 10 were all normal. The authors conclude that that modern and
      reproducible management of TGA is possible in an inter-regional centre with
      results comparable to those of surgical centres of reference.

PMID- 16802734
TI  - [Value of the Norwood-Sano compared with the classical Norwood procedure in
      hypoplastic left heart syndrome].
AB  - Palliative treatment of the hypoplastic left heart syndrome is rarely practiced
      in France because of the poor prognosis of the first surgical stage of the
      Norwood procedure. The recent modification proposed by Sano seems to give more
      promising results. The authors report their experience with the Norwood-Sano
      procedure compared with the classical Norwood procedure in 13 neonates with
      hypoplasia of the left heart. From 1999 to 2005, 8 patients underwent the
      classical Norwood procedure (1999-2001) and 5 had the Sano modification (2002
      2005). During the preoperative period, there was 1 case of a very restrictive
      interatrial septum and 5 patients required mechanical ventilation. The patients
      were operated at an average age of 8.5 +/- 12 days. The results showed that
      survival after the first surgical stage was significantly better with the Sano
      modification (12.5% versus 80%; p= 0.03). All patients who survived the first
      stage went on to the second stage with a bi-directional right superior cavo
      pulmonary derivation at an average of 6.1 +/- 2.4 months. Despite the
      infundibulotomy of the Sano modification, no arrhythmia or right ventricular
      dysfunction was observed after an average follow-up of 21.7 +/- 7.6 months. The
      authors conclude that the Sano modification improved survival of patients with
      hypoplasia of the left heart after the first palliative surgical procedure. The
      long-term follow-up of patients operated by this technique should particularly
      look out for arrhythmias and right ventricular dysfunction.

PMID- 16802735
TI  - [The effect of an endothelin receptor antagonist in Eisenmenger syndrome: a
      single-center experience of 11 patients].
AB  - The Eisenmenger syndrome is a complication of congenital heart disease with
      significant left-to-right shunts, such as large ventricular septal defects, and
      corresponds to fixed pulmonary hypertension with shunt reversal. Bosentan, an
      inhibitor of endothelin A and B receptors, is a new molecule previously validated
      in the treatment of primary pulmonary hypertension. The authors report their
      monocentric experience of bosentan in 11 consecutive patients with the
      Eisenmenger syndrome treated for at least one year. This retrospective study
      comprised 7 females and 4 males with an average age of 34 years (range 17 to 51
      years). The underlying lesion was ventricular septal defect (n = 4), atrial
      septal defect (n = 3), pulmonary atresia with septal defect (n = 4 of which 2
      were treated palliatively). Before treatment, the patients were classified
      according to the NHYA functional class (I, II, IIIa and IIIb, IV or, respectively
      from 1 to 5) with a distribution in this series between Classes IIIa and IV
      (average 3.81 +/- 0.75) and from 3 to 10 on Borg's dyspnoea scale (average 6.54
      +/- 2.29). The ambient oxygen saturation (SaO2) at rest was, on average 77 +/-
      9%, the haemoglobin concentration 16.6 +/- 2.4 g/dl; hepatic transaminase levels
      were normal. The 6 minute walk test before treatment was 216 +/- 111 m with
      marked desaturation on exercise (49 +/- 18%). With Bosentan, patients were
      globally much better clinically with a decrease in dyspnoea, improvement in NHYA
      class and increased 6 minute walking perimeter. Improvement in NYHA class was
      observed from 3 months' treatment (3.0 +/- 0.8, p = 0.0002) and was sustained to
      one year (2.54 +/- 0.7, p< 0.001). An improvement of dyspnoea on Borg's scale was
      observed from the second month's treatment (5.56 +/- 1.65, p = 0.0201) and
      persisted throughout follow up to one year (3.81 +/- 1.32, p < 0.0001).
      Similarly, the 6 minute walking perimeter increased from the first control at 6
      months (323 +/- 82 m, p < 0.0001) and at one year (322 +/- 62 m, p <0.0004).
      Finally, although a significant increase in SaO2 was observed at 6 months (p =
      0.0032), this was hardly significant at one year (82 +/- 10 %, p = 0.0512).
      Transaminase levels did not rise significantly at the follow up visits (p = ns)
      and the haemoglobin concentration was unchanged. No patient died during the study
      period. This study showed a clear functional improvement in patients with
      Eisenmenger's syndrome treated with bosentan. The drug was well tolerated
      clinically with few adverse effects and a good safety margin of usage.

PMID- 16802736
TI  - [Quality of life of patients with total cavopulmonary anastomosis].
AB  - INTRODUCTION: Total cavo-pulmonary connection (TCPC) represents the current
      surgery standard for congenital univentricular heart disease (CUHD) patients. We
      studied the health related quality of life (HRQOL) expressed by TCPC operated
      patients. PATIENTS AND METHODS: This transversal study is based on 24 children
      and 10 adult TCPC patients aged from 5 to 41 years old. The HRQOL evaluation
      relies on generic self report instruments such as the PedsQL 4.0 for the children
      and their parents, and the Duke Health profile for the adult patients. Additional
      questions were specifically designed for this study as well. RESULTS AND
      DISCUSSION: The estimated HRQOL is 68.15 for the children and 68.71 for their
      parents. In these young cases, the global HRQOL or some specific score are
      altered when any comorbidity or scholar difficulties are present, or when TCPC
      was performed more than 10 years ago. The estimated HRQOL is 74.67 in adulthood.
      In these patients, the young age, the lifestyle, the onset of more than 2 early
      complications ans the necessity of anti-arrhythmia therapy decrease various HRQOL
      scores. The physical handicap is considered as the major limitation for children
      and adult patients. Thanks to adaptative and cognitive compensatory mechanisms,
      such as resilience, both groups express a satisfying HRQOL assessment.
      CONCLUSION: Our study indicates that TCPC provides a good HRQOL in CUHD patients
      despite the complex management and follow-up of these diseases, the risk of
      complication onset and the physical handicap usually observed.

PMID- 16802737
TI  - [New approach to perimembranous ventricular septal defect by real-time 3D
      echocardiography].
AB  - Perimembranous ventricular septal defects (VSD) have a close anatomical
      relationship to the aortic and tricuspid valve which may make percutaneous
      closure difficult. The authors' objective was to study the anatomy of
      perimembranous VSD by real-time 3D echocardiography. Fourteen patients aged 1 day
      to 3 years (mean 3 months) underwent transthoracic 2D and 3D echocardiography.
      Two patients (> 10 kg) underwent closure of the perimembranous VSD with an
      Amplatzer occluder. The other 12 patients were operated (surgical closure in 11
      and circling suture with resorbable thread in 1 patient). The 3D echocardiography
      showed variations in the geometry of the perimembranous VSD (eccentric, oval,
      cleft). The maximal diameter of the septal defect by 3D echocardiography was on
      average 2 mm greater than the diameter by 2D echocardiography. The 3D echo
      enabled visualisation of the close relationship of the septal tricuspid leaflet,
      the aortic valve and the perimembranous VSD, showing the mechanism of its closure
      and the associated aortic regurgitant lesions. The profile of the prosthesis
      implanted percutaneously was well shown in the different 3D views. The authors
      conclude that real-time 3D echocardiography is a technique which allows accurate
      anatomic description of perimembranous VSD. As a complement to classical 2D
      methods, it gives a better appreciation of the maximal diameter of the septal
      defect and of its relationship to the aortic and tricuspid valves.

PMID- 16802738
TI  - [B-natriuretic peptide and cardiological emergencies in childhood].
AB  - The increase in B-natiuretic peptide (BNP) is well correlated with cardiovascular
      symptoms in adults. Its use in children is recent and only partially evaluated.
      The authors undertook a prospective study of BNP concentrations and its kinetics
      in 54 children with an average age of 15 months (5 days to 11 years) admitted as
      paediatric emergencies. The symptoms were dyspnoea (60%), shock (15%), suspicion
      of Kawasaki disease (15%) and other (10%). Twenty children had BNP levels of more
      than 100 pg/ml related to decompensation of known congenital heart disease in 7
      patients (average BNP 462 +/- 323 pg/ml), due to neonatal coarctation in 2
      patients (BNP > 3000 pg/ml), due to cardiomyopathy in 6 patients (BNP= 2576 +/-
      1215 pg/ml), due to an arrhythmia in 1 patient (BNP= 3754 pg/ml) and to Kawasaki
      disease in 4 patients (BNP= 521 +/- 448 pg/ml). Thirty-four children had BNP
      values of less than 100 pg/ml; 29 had no cardiac disease and 5 had known
      congenital heart disease with other symptoms. Measuring BNP is quick and
      economical and is a valuable aid in the diagnosis of cardiac dysfunction in
      symptomatic children in the emergency room. High BNP values seem to be correlated
      with the severity of the cardiac disease. Low BNP values seem to have a good
      negative predictive value in children without underlying cardiac disease. The
      interpretation of intermediary values, especially when there is previous cardiac
      disease, is more difficult in view of the absence of known threshold values for
      different haemodynamic situations. Further studies are required to determine the
      value of this test for the follow-up and setting up of prognostic values in
      children with congenital heart disease.

PMID- 16802739
TI  - [Fetal haemodynamic and left heart dysfunction].
AB  - Foetal cardiology is a well established field of paediatric cardiology. It is no
      longer a simple exercise of prenatal diagnosis of cardiac malformations. It also
      covers the investigation and treatment of arrhythmias and functional and dynamic
      cardiocirculatory evaluation of the foetus which does not always have primary
      organic cardiac disease. It is this aspect which will be described in this
      article. The interactions of the left heart / foetal haemodynamics are classified
      in two main groups according to whether the left myocardial dysfunction is
      primary or secondary to changes of pre- or afterload. The haemodynamics
      singularities of the normal foetal circulation are and essential basis for the
      understanding of the phenomena observed.

PMID- 16802740
TI  - [Left heart defects and genetics].
AB  - The obstructive cardiac defects of the left heart are an heterogeneous group of
      malformations. These past years their molecular bases have been partially
      understood. The associated chromosomal anomalies are mainly represented by the
      Turner syndrome, the microdeletion of the chromosome 11q and the 7q23 deletion in
      Williams syndrome. In isolated obstructive left heart diseases, new insights into
      their genetic bases have been made because the dominant inheritance has been
      demonstrated and the notion of a phenotypic continuum between bicuspid aortic
      valve and the complete form of hypoplastic left heart has been proposed. Finally,
      mutations in genes involved in heart development, namely NKX2.5 and NOTCH1, have
      been identified in these defects and support the former hypotheses. The low
      penetrance and the variable expression of these known mutations did not
      completely solved prenatal genetic counselling.

PMID- 16802741
TI  - [Multislice CT scan in congenital heart disease].
AB  - The management of congenital cardiovascular malformations is a diagnostic
      challenge. It requires accurate assessment of the intra- and extra-cardiac
      malformations. Three-dimensional imaging by the multislice CT scanner is now a
      routine investigation for congenital heart disease, complementary to
      echocardiography, and, increasingly, an alternative to conventional angiography.
      Three dimensional imaging is particularly useful in the diagnosis of complex
      congenital heart disease, in the preparation of complex investigations of
      interventional cardiac catheterisation and the postoperative evaluation of
      surgical repair. This report describes the different acquisition protocols
      adapted for children and illustrates the present role of volumic CT scanner in
      congenital heart disease by clinical examples of everyday clinical practice.

PMID- 16802742
TI  - [Transcatheter exclusion of a giant aneurysm of the left pulmonary artery using
      covered stents].
AB  - An 11 year-old boy with an Alagille syndrome was referred for an urgent
      echocardiography because of new onset of febrile hemoptysis. Follow-up in our
      institution to that point had shown severe hypoplastic pulmonary arteries. The
      diagnosis of tricuspid endocarditis complicated by pulmonary embolisms and
      aneurysm of the left pulmonary artery was done. Despite effective antiobiotics,
      the evolution was marked by rapid progression in size of the left pulmonary
      aneurysm. Since the surgery was not an option because of high risk of death, this
      aneurysm was treated by a trans-catheter technique using covered stents (CP
      stents, Numed Inc). Its exclusion allowed to stop its progression in size and to
      avoid its rupture.

PMID- 16802743
TI  - [Implantation of mechanical pulmonary and tricuspid valve prostheses at a
      distance from complete repair of Tetralogy of Fallot].
AB  - The authors report the case of a 39 years old woman operated for tetralogy of
      Fallot at the age of 6. Multiple complications due to postoperative
      atrioventricular block and a poor surgical result on the pulmonary outflow tract
      led to several reoperations. Right ventricular dysfunction with pulmonary
      regurgitation and mitral tricuspid valve disease in a context of endocarditis on
      the pacing catheter led to double pulmonary and tricuspid valve replacement with
      mechanical prostheses. The outcome at follow-up at 3 years is good. To the
      authors' knowledge, this is the first reported case of double mechanical valve
      replacement of the right heart after complete repair of tetralogy of Fallot.

PMID- 16802744
TI  - [Mycoplasma pneumoniae myopericarditis in children].
AB  - Mycoplasma pneumoniae myocarditis is a rare condition, potentially very serious
      and seldom described in children. It is classically attributed to direct invasion
      or to an indirect immunological mechanism. The authors report the case of a 10
      year old boy with myopericarditis, proved by authentic seroconversion,
      complicating congenital mitro-aortic valvular disease. In this case, the
      spectacular response to steroid therapy was in favour of an indirect
      immunological causal mechanism of the left ventricular dysfunction and
      pericardial involvement.

PMID- 16802745
TI  - [Fulminant influenza type A associated myocarditis: a fatal case in an 8 year old
      child].
AB  - Fulminant Influenza type A-associated myocarditis are very rare in children. The
      clinical presentation is non specific, like flu illness, cardiogenic shock or
      sudden cardiac arrest. We report the case of a eight years old girl with a
      fulminant Influenza A-associated myocarditis with a fatal evolution despite the
      use of an extracorporeal membrane oxygenation (ECMO). The aim of this observation
      is to remind that influenza in children, usually considered as a benign illness,
      can exceptionally be complicated by a fulminant myocarditis. Because the
      possibility to recover a full myocardial function, the persistence of severe
      heart failure despite the medical treatment should conduct rapidly to a
      mechanical circulatory assistance.

PMID- 16802746
TI  - [Unusual outcome of mitral valve infectious endocarditis in a premature infant].
AB  - The authors report a case of Staphylococcus Aureus infectious endocarditis in a
      premature baby. Echocardiography on the 8th day of life showed a large vegetation
      on the anterior mitral leaflet without significant regurgitation. Intravenous
      antibiotics and platelet antiaggregant therapy were given. At three weeks of age
      the vegetation split into two, one part attached to the foramen ovale and the
      other to the anterior mitral leaflet. At one month, the development of severe
      mitral regurgitation led to surgical valvuloplasty in a 2 kg neonate, the
      vegetation on the foramen ovale having spontaneously fragmented. The ablation of
      the mitral vegetation associated with commissuroplasty reduced the mitral
      regurgitation. At 3 months after surgery, the child was asymptomatic with a
      minimal mitral regurgitation.

PMID- 16802747
TI  - [Neonatal hypocalcaemic dilated myocardiopathy due to a 22q11 microdeletion].
AB  - Here we report 2 cases of hypocalcemic cardiomyopathy revealing a 22q11
      microdeletion syndrome. This presentation at diagnosis is rare as the cardiac
      phenotype is mainly made of conotruncal congenital heart defects in this
      condition. Cardiac failure was diagnosed during the neonatal period in the 2
      cases and was associated with profound hypocalcemia. As usual, treatment with
      calcium and vitamin D led to the regression of the hypocalcemia and the left
      ventricular function was fully restored. While this circumstances are unusual, we
      recommend that screening for 22q11 deletion should be performed when confronted
      to hypocalcemic cardiomyopathy or left ventricular systolic dysfunction in
      conotruncal defects in neonates.

PMID- 16802748
TI  - [A rare association of double discordance with aortic arch anomalies: value of
      multislice CT scan].
AB  - The authors report the case of a 14 month old infant admitted for intermittent
      stridor. Routine echocardiography showed atrioventricular and ventriculo-arterial
      discordance with an intact septum and situs solitus with levocardia. Multislice
      CT scan showed tracheal compression due to a Neuhauser anomaly of the aortic
      arches. The paucity of symptoms led to surgical abstention.

PMID- 16802749
TI  - [Coarctation of the aorta presenting as a pulsatile occipital mass].
AB  - A healthy 18 months old boy, is referred to our hospital for a thrilling
      pulsatile mass behind the left ear. Aortography in the ascending aorta shows a
      severe coarctation with almost interruption of the aorta between the left carotid
      and left subclavian artery. Both external carotid arteries provide an important
      collateral pathway through occipital arteries to two dilated vertebral arteries.
      Descending aorta is feeding by a reverse blood flow into vertebral and subclavian
      arteries. The child has been operated. This is an original presentation of severe
      coarctation of the aorta with development of an important and vital collateral
      pathway.

PMID- 16802750
TI  - [Spontaneous idiopathic chylopericardium in childhood].
AB  - Here we report a case of a primary idiopathic chylopericardium in a 13 years old
      child. Pericardial effusion was diagnosed because the child suffered chest pain
      and fatigue. Pericardial drainage was performed and 800mL of chylous fluid was
      evacuated. Extensive investigations were performed but no cause could be found.
      Thoracic CT scan, lymphoscintigraphy and MRI did not evidence any communication
      between the thoracic duct and pericardium. After 2 recurrences of pericardial
      effusion while the child was on a medium chain triglycerides regimen, it was
      decided to ligate the thoracic duct and to do a partial pericardectomy. The
      result was excellent with complete resolution of the pericardial effusion and no
      recurrence since 3 years.

PMID- 16802752
TI  - Correction: Accreditation Participation Requirement 8.

PMID- 16802751
TI  - [Recommendations for the medical management of aortic complications of Marfan's
      syndrome].

PMID- 16802753
TI  - Clarification: Standard QC.1.40, element of performance 4.

PMID- 16802754
TI  - Revisions to standard LD.3.110.

PMID- 16802755
TI  - Revisions to the Management of Human Resources chapter, credentialing and
      privileging standards, and laboratory standards.

PMID- 16802756
TI  - Revisions to standard EC.7.40.

PMID- 16802757
TI  - New infection control requirement for offering influenza vaccination to staff and
      licensed independent practitioners.

PMID- 16802758
TI  - Perennial ryegrass.

PMID- 16802759
TI  - The inner-city asthma epidemic reaches far and wide.

PMID- 16802760
TI  - Vocal cord dysfunction: ready for prime-time?

PMID- 16802761
TI  - How well do counts add up?

PMID- 16802762
TI  - Do HLA genes play a role in the genetics of peanut allergy?

PMID- 16802763
TI  - Osteoporosis and asthma.
AB  - OBJECTIVE: To summarize the etiology, evaluation, prevention, and management of
      osteoporosis in a patient with asthma and worsening osteoporosis, a problem that
      is frequently encountered in an allergy-immunology practice, and the incidence,
      risk factors, screening guidelines, and recommended prevention and treatment
      options for this disease. DATA SOURCES: MEDLINE was searched for relevant English
      language review articles published between January 1993 and March 2006 using the
      keyword osteoporosis in combination with asthma or COPD (chronic obstructive
      pulmonary disease). Additional sources and studies cited include relevant
      references from the official guidelines of the national medical associations,
      including the National Osteoporosis Foundation, the American College of
      Rheumatology, the World Health Organization, and the National Institutes of
      Health Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and
      Therapy. STUDY SELECTION: The authors selected the most relevant and recent
      sources for inclusion in this review. RESULTS: As the population ages,
      osteoporosis continues to increase in prevalence and severity. Screening rates of
      patients at risk of osteoporosis are suboptimal. A variety of effective treatment
      options are available for osteoporosis prevention and therapy. CONCLUSION:
      Patients with asthma and chronic obstructive pulmonary disease are at risk of
      osteoporosis, especially those patients who are treated with high doses of
      corticosteroids. Specialist physicians should be knowledgeable about the
      screening guidelines, counseling, and therapeutic options for the prevention and
      management of osteoporosis.

PMID- 16802764
TI  - The role of antileukotriene therapy in seasonal allergic rhinitis: a systematic
      review of randomized trials.
AB  - OBJECTIVE: To evaluate the effect of oral leukotriene receptor antagonists as
      monotherapy or combined with other drugs in the treatment of seasonal allergic
      rhinitis. DATA SOURCES: The MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing
      and Allied Health), and Cochrane databases; review articles; and references of
      included trials. STUDY SELECTION: Published (1966-2005) randomized controlled
      trials with nasal and eye symptoms and quality-of-life scores as primary
      outcomes. RESULTS: Seventeen studies including 6,231 adults with seasonal
      allergic rhinitis were selected. Oral leukotriene antagonists significantly
      reduced daytime nasal symptoms (standardized mean difference [SMD], -0.24; 95%
      confidence interval [CI], -0.33 to -0.16), nighttime nasal symptoms (SMD, -0.23;
      95% CI, -0.30 to -0.16), and eye symptoms and significantly improved quality of
      life compared with placebo. There were no significant differences between oral
      leukotriene antagonists and oral histamine H1 antagonists on nasal and eye
      symptoms and quality-of-life overall score. We also found that leukotriene
      receptor antagonists were inferior to intranasal corticosteroids for decreasing
      daytime (SMD, 0.41; 95% CI, 0.27 to 0.56) and nighttime nasal symptoms. The
      combination of leukotriene receptor antagonists plus histamine H1 antagonists
      produced greater relief of eye symptoms compared with histamine H1 antagonists
      alone. Finally, intranasal corticosteroids significantly reduced nasal congestion
      compared with leukotriene receptor antagonists plus histamine H1 antagonists.
      CONCLUSIONS: Leukotriene receptor antagonists were better than placebo,
      equivalent to oral histamine H1 antagonists, and inferior to intranasal
      corticosteroids for treating seasonal allergic rhinitis. Alternatively,
      leukotriene receptor antagonists plus histamine H1 antagonists were more
      effective than histamine H1 antagonists alone but inferior to intranasal
      corticosteroids.

PMID- 16802765
TI  - Symptom profile and asthma control in school-aged children.
AB  - BACKGROUND: Children with poorly controlled asthma are at high risk of airway
      remodeling, sleep disruption, school absenteeism, and limited participation in
      activities. OBJECTIVE: To determine asthma prevalence and characterize disease
      severity and burden in school-aged children. METHOD: A case-finding study was
      conducted via a multiple-choice questionnaire and asthma algorithm. Items used
      for analysis include physician diagnosis of asthma, symptom severity, and health
      care utilization. The chi2 test was used to determine the significance of
      differences among cases. Logistic regression was used to evaluate the association
      of patient factors and asthma indicators. RESULTS: Of the 5,417 children
      surveyed, 1,341 (25%) were classified as being at risk of asthma. Of these asthma
      cases, 55% were positive by diagnosis and algorithm (active), 10% were positive
      per algorithm alone (suspected), and 35% were positive per diagnosis alone
      (nonactive). Only 14% of all asthma cases reported experiencing no respiratory
      symptoms (< 1% active, 2% suspected, and 40% nonactive) compared with 75% of
      noncases. Also, 75% of noncases reported never missing school compared with 19%,
      33%, and 54% of active, suspected, and nonactive asthma cases. African American
      race, Medicaid enrollment, and male sex were independent predictors of asthma
      risk. Similarly, African American race, Medicaid enrollment, age, and persistent
      asthma were independent predictors of emergency department use among asthma
      cases. DISCUSSION: Prevalence of active symptoms suggestive of poor asthma
      control was extremely high among urban, minority children enrolled in Arkansas'
      largest public school district. Poor asthma control greatly affects quality of
      life, including school attendance and performance. Interventions should raise
      expectations and emphasize the importance of achieving asthma control.

PMID- 16802766
TI  - Long-term outcome of vocal cord dysfunction.
AB  - BACKGROUND: Vocal cord dysfunction (VCD) is an involuntary functional disorder
      commonly misdiagnosed as asthma. Previous reports describe the disorder and
      treatment but not the long-term outcome. OBJECTIVE: To determine the long-term
      outcome of VCD. METHODS: A retrospective medical record review identified 49
      patients, ages 8 to 25 years, diagnosed as having VCD from 1989 to 2002.
      Telephone contact was attempted in all. RESULTS: Of the 49 patients, 41 had
      previously been treated for asthma; that diagnosis was confirmed by us as a
      comorbidity in only 12 patients. Two distinct phenotypes of VCD were observed.
      Symptoms were limited to exercise-induced VCD (EIVCD) in 29 and spontaneously
      occurring VCD (SVCD) in 20, only 4 of whom additionally had EIVCD. Twenty-eight
      of the 49 were successfully contacted by telephone. Eight of the 11 contacted
      patients with SVCD followed the recommendation to see our speech therapist, all
      of whom learned to control symptoms. However, 2 who also had EIVCD continued with
      that problem. Pretreatment with an anticholinergic inhaler prevented EIVCD in 6
      patients in whom this was tried. Complete absence of symptoms, at times ranging
      from 1 week to 5 years (median, 5 months), was reported in 26 of the 28 contacted
      patients. CONCLUSIONS: VCD continues to be frequently misdiagnosed as asthma. Two
      phenotypes of VCD are apparent: EIVCD and SVCD. Speech therapy provides relief of
      symptoms for SVCD. Prevention of EIVCD with an anticholinergic inhaler in 6
      patients suggests that a controlled clinical trial is warranted. Regardless of
      treatment, eventual spontaneous resolution was common.

PMID- 16802767
TI  - Linear growth in prepubertal asthmatic children treated with montelukast,
      beclomethasone, or placebo: a 56-week randomized double-blind study.
AB  - BACKGROUND: Antileukotrienes and inhaled corticosteroids are asthma controller
      agents widely used in the treatment of pediatric asthma. OBJECTIVE: To evaluate
      the effects of montelukast and beclomethasone on linear growth in prepubertal
      asthmatic children for 1 year. METHODS: This was a 30-center study of boys (6.4
      9.4 years old) and girls (6.4-8.4 years old) at Tanner stage I with mild,
      persistent asthma. After a placebo run-in period, 360 patients were randomized in
      equal ratios to double-blind, double-dummy treatment with 5 mg of montelukast,
      200 microg of beclomethasone twice daily (positive control), or placebo for 56
      weeks; 90% of the patients completed the study. The primary end point was linear
      growth velocity, measured using a stadiometer. RESULTS: Linear growth rates were
      similar between the montelukast and placebo groups; the mean difference for the
      year was 0.03 cm. The mean growth rate with beclomethasone was significantly less
      than with placebo (-0.78 cm) or montelukast (0.81 cm) (P < .001 for both). Median
      percentage of days with beta-agonist use was greater with placebo (14.58%) vs
      montelukast (10.55%) or beclomethasone (6.65%) (P < .05 for all). More patients
      used oral corticosteroid rescue with placebo (34.7%) than with montelukast
      (25.0%) or beclomethasone (23.5%). An imbalance in bone marker levels was seen
      with beclomethasone but not with montelukast. CONCLUSION: In prepubertal
      asthmatic children, montelukast did not affect linear growth, whereas the growth
      rate with beclomethasone was significantly decreased during 1 year of treatment.

PMID- 16802768
TI  - Efficacy and safety of inhaled fluticasone propionate chlorofluorocarbon in 2- to
      4-year-old patients with asthma: results of a double-blind, placebo-controlled
      study.
AB  - BACKGROUND: Current asthma guidelines recommend inhaled glucocorticoids
      administered via pressurized metered-dose inhaler (MDI) with a holding chamber as
      the preferred therapy for young children with asthma. OBJECTIVE: To evaluate the
      efficacy and safety of fluticasone propionate chlorofluorocarbon MDI use in
      preschool-aged children with asthma. METHODS: Randomized, double-blind, placebo
      controlled, parallel-group study of 332 children aged 24 to 47 months with
      asthma. Fluticasone propionate chlorofluorocarbon, 44 or 88 microg twice daily,
      or placebo (chlorofluorocarbon propellant alone) administered for 12 weeks via
      MDI with a valved holding chamber and an attached face mask. The primary efficacy
      measure was average change in 24-hour daily asthma symptom scores. Safety
      assessments included adverse events, 12-hour urinary cortisol excretion, and
      growth. RESULTS: Treatment failure (ie, asthma exacerbation) occurred in
      approximately half as many fluticasone propionate-treated patients (13%-14%) as
      placebo-treated patients (24%). Compared with placebo users, patients treated
      with fluticasone propionate, 88 microg twice daily, had a 13% greater improvement
      in the mean proportion of symptom- and albuterol-free days (P = .02); asthma
      symptom scores and albuterol use were also significantly reduced. Patients
      treated with fluticasone propionate, 44 microg twice daily, had greater
      improvements than placebo-treated patients; however, differences did not reach
      statistical significance. At end point, the growth velocities of fluticasone
      propionate-treated patients were within the range of those of placebo-treated
      patients. No clinically relevant changes in 12-hour overnight urinary cortisol
      excretion were observed. CONCLUSION: Compared with placebo use, fluticasone
      propionate, 88 microg administered twice daily, significantly reduced asthma
      exacerbations, asthma symptoms, and rescue albuterol use and was well tolerated,
      with no clinically relevant systemic effects, as measured by growth velocity or
      12-hour urinary cortisol excretion levels.

PMID- 16802770
TI  - Interpreting quality-of-life data: methods for community consensus in asthma.
AB  - BACKGROUND: Change in health-related quality of life (HRQoL) is an important
      outcome in asthma treatment. Patient and provider consensus on how to determine
      thresholds for identifying important improvements and declines, however, has not
      been achieved. OBJECTIVE: To search for consensus in clinically important
      difference (CID) thresholds for HRQoL change from 3 points of view: (1) an expert
      panel of physicians who treat patients with asthma and measure the HRQoL of their
      patients, (2) asthmatic patients, and (3) the primary care physicians (PCPs) of
      these asthmatic patients. METHODS: The expert panel used Delphi and consensus
      methods to agree on CID levels for the Asthma Quality of Life Questionnaire and
      the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2.0. A total
      of 396 patients attending midwestern primary care clinic sites completed these
      interviews bimonthly for 1 year. The 46 PCPs treating these patients completed
      baseline assessments on each patient's asthma and then evaluated the change in
      each patient's condition at subsequent office visits during the next year.
      RESULTS: The patient-perceived estimates were consistent with results of previous
      studies but were notably lower than those derived from the expert panel and the
      PCPs. The Short-Form Health Survey generally did not provide sufficient
      sensitivity to detect important changes. CONCLUSIONS: Although consensus on the
      interpretation of change in HRQoL measures was not achieved, this evidence-based
      approach demonstrates the value of patient and physician perspectives and the
      need for improved dialogue and understanding to optimize the HRQoL of patients
      with asthma.

PMID- 16802769
TI  - The role of chemokines in exercise-induced bronchoconstriction in asthma.
AB  - BACKGROUND: The pathogenesis of exercise-induced bronchoconstriction in asthma is
      incompletely understood, and the role of chemokines has not been investigated.
      OBJECTIVE: To investigate the involvement of the CC chemokines eotaxin, regulated
      upon activation normal T-cell expressed and secreted (RANTES), thymus and
      activation-regulated chemokine (TARC), and the CXC chemokine interferon-gamma
      inducible protein 10 (IP-10) in exercise-induced bronchoconstriction. METHODS:
      Four groups were enrolled: asthmatic children with positive (n = 15) and negative
      (n = 15) responses to exercise, children with cystic fibrosis (n = 14), and
      healthy children (n = 11). Levels of eotaxin, RANTES, TARC, and IP-10 were
      determined in plasma before, immediately after, and 6 and 24 hours after exercise
      challenge using enzyme-linked immunosorbent assay. Transcriptional activity was
      measured using reverse transcriptase-polymerase chain reaction. RESULTS: Exercise
      did not induce any significant changes in systemic chemokine levels. A
      significant difference was observed only in the preexercise IP-10 levels among
      groups (P = .045). There was a significant difference in peripheral blood
      eosinophil counts among groups (P = .003). In asthmatic children with a positive
      response to exercise, there was an inverse correlation between eosinophil counts
      and eotaxin levels (r = -0.616; P = .01) and between forced expiratory volume in
      1 second and TARC levels (r = -0.865; P = .001). Reverse transcriptase-polymerase
      chain reaction studies did not show any difference in the transcription of the
      chemokines. CONCLUSIONS: Exercise does not cause any changes in the systemic
      expression of eosinophilic chemokines. Peripheral blood eosinophils may be a
      determinant of the exercise response, and eotaxin and TARC may be associated with
      eosinophil counts and forced expiratory volume in 1 second in children with a
      bronchoconstrictor response to exercise.

PMID- 16802771
TI  - Allergy skin test responses during experimental infection with respiratory
      syncytial virus.
AB  - BACKGROUND: Allergy skin testing is one of the most frequently performed
      physician office procedures. Many factors can affect the results of those tests,
      including the well-defined suppressive effect of systemic antihistamines. False
      positive allergen skin test results are known to occur; however, contributing
      factors are not well understood. OBJECTIVE: To determine whether a viral upper
      respiratory tract infection affects allergy skin test responsiveness. METHODS: We
      performed skin tests with histamine and a panel of geographically relevant
      inhalant allergens on 16 adults before and 3, 6, and 21 days after experimental
      exposure to respiratory syncytial virus (RSV), a virus that causes signs and
      symptoms of a cold. RESULTS: The RSV exposure, with and without documented
      infection, caused increased wheal and flare areas to histamine and allergen and
      de novo positive allergen test responses in individuals with no measurable
      responses at baseline. These were noted as late as 21 days after RSV exposure and
      may be consistent with mediation by up-regulated neurogenic inflammation during
      RSV infection. CONCLUSION: These results may have implications for explaining the
      cause of such well-known complications of RSV infection as otitis media,
      bronchiolitis, and asthmatic exacerbation.

PMID- 16802772
TI  - Latex allergen IgE assays in the assessment of Veterans Affairs health care
      workers.
AB  - BACKGROUND: A previous multicenter study of Veterans Affairs health care workers
      evaluated hospital participants for latex hypersensitivity. Well-defined groups
      from that study allowed us to explore the diagnostic utility of newer antilatex
      allergen IgE immunoassays in the present study. OBJECTIVES: To determine whether
      an enhanced CAP (ENHCAP) assay or an enzyme-linked immunosorbent assay (ELISA)
      identifies latex glove symptomatic individuals with antilatex allergen IgE that
      had not been detected by the CAP assay used in the original study and to
      determine the specificity of the ENHCAP assay. METHODS: The ELISA measured IgE
      antibody to Malaysian nonammoniated natural rubber latex extract (MNA), Hev b1,
      Hev b5, and Hev b6. Four patient groups were tested: confirmed latex glove
      allergic, latex glove symptomatic, latex glove sensitized/asymptomatic, and latex
      glove nonallergic. RESULTS: The ENHCAP assay and the MNA ELISA were highly
      concordant with the original CAP assay. In the subgroup with latex glove symptoms
      that were previously negative by the CAP assay, the ENHCAP assay value was
      elevated in 7 (11%) of 64 samples, only 3 of which were class 2 or higher. The
      MNA ELISA result was positive in only 4 (6%) of these 64 samples, and 3 of these
      were fractionally above the cutoff value for this assay. CONCLUSIONS: The ENHCAP
      assay and the MNA ELISA identified a few additional positive individuals in the
      group that was latex glove symptomatic and originally CAP assay negative. The
      ENHCAP assay and the MNA ELISA produced only a modest improvement in diagnostic
      sensitivity over that of the original CAP assay.

PMID- 16802773
TI  - Effect of a Chinese herbal formula, Shi-Bi-Lin, on an experimental model of
      allergic rhinitis.
AB  - BACKGROUND: Jia Wei Cang Er Zi San, a traditional Chinese herbal formula, has
      been used to treat allergic rhinitis (AR) for several centuries. However, its
      effect on experimental animal models and its therapeutic mechanism remain
      unclear. OBJECTIVE: To study the effect of Shu-Bi-Lin, a modified Jia Wei Cang Er
      Zi San, on an animal model of AR. METHODS: Shu-Bi-Lin was administered to the
      guinea pig model of AR. Meanwhile, an antihistamine-treated group for the
      treatment control, an ovalbumin-sensitized and untreated group for the positive
      control, and a sham-sensitized, sham-challenged group for the sham control were
      studied in parallel. Symptomatic and some pathophysiologic variables were
      evaluated. RESULTS: Sneezing and nasal scratching after challenges were
      significantly ameliorated in the Shu-Bi-Lin-treated group compared with the
      ovalbumin-sensitized and untreated group, but rhinorrhea volume was not reduced.
      Shu-Bi-Lin significantly suppressed the production of IgG1 in the passive
      cutaneous anaphylaxis test. The thromboxane B2 level in nasal lavage fluid was
      significantly deceased in the Shu-Bi-Lin-treated group; however, the reduction in
      histamine and peptide leukotriene levels did not reach statistical significance.
      In addition, eosinophil infiltration and endothelial nitric oxide synthase
      immunoreactivity in the nasal tissues were reduced in the Shu-Bi-Lin-treated
      group. CONCLUSIONS: Shu-Bi-Lin could alleviate the nasal symptoms of AR, and its
      mechanism might be related to its inhibitory effect on type I anaphylaxis
      reactions and eosinophil infiltration in the nasal tissues, as well as the
      inhibition of some mediators related to AR.

PMID- 16802774
TI  - Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for
      the treatment of seasonal allergic rhinitis symptoms.
AB  - BACKGROUND: Few studies have directly compared the efficacy of intranasal
      corticosteroids with that of leukotriene receptor antagonists for the treatment
      of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE:
      To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with
      oral montelukast, 10 mg daily, for the relief of SAR symptoms. METHODS: Patients
      with SAR 15 years or older were randomized to receive either fluticasone
      propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy,
      parallel-group study. The primary efficacy measure was the mean change from
      baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime
      individual nasal symptom scores [INSSs] assessing nasal congestion, itching,
      rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy
      measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime
      INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime
      awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2. RESULTS:
      Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P <
      .001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed
      significant differences favoring fluticasone propionate over montelukast across 2
      weeks of treatment. CONCLUSION: Compared with montelukast, fluticasone propionate
      provided significantly greater improvement in daytime and nighttime SAR symptoms.

PMID- 16802775
TI  - Correlation between Olea europaea and Parietaria judaica pollen counts and
      quantification of their major allergens Ole e 1 and Par j 1-Par j 2.
AB  - BACKGROUND: In patients with pollinosis, allergic symptoms are often correlated
      with the number of airborne pollen grains, although this correlation is not
      always close. The direct measurement of the concentration of aeroallergens has
      only recently been introduced and is an important advance in public health
      information systems. OBJECTIVE: To compare specific quantification of
      aeroallergens Ole e 1 and Par j 1-Par j 2 Olea and Urticaceae pollen counts.
      METHODS: The Hirst method sampler and the Burkard Cyclone sampler were used for
      pollen count and allergen quantification, respectively. The aerosol was extracted
      and quantified for Ole e 1 and Par j 1-Par j 2 content using enzyme-linked
      immunosorbent assay procedures. RESULTS: Day-to-day variations were observed in
      both the pollen count and the amount of allergens. Pollen counts and aeroallergen
      quantification were closely correlated with 99% significance (Olea/Ole e 1: R =
      0.892, P < .001; Urticaceae/Par j 1-Par j 2: R = 0.734, P < .001). CONCLUSION:
      The technique for the sampling and quantification of aeroallergens presented in
      this article, based on enzyme-linked immunosorbent assay and applied to the
      protein extracts directly obtained from the bioaerosol, represents an important
      advance in the epidemiologic study of allergic respiratory diseases.

PMID- 16802776
TI  - Lack of association of HLA class II alleles with peanut allergy.
AB  - BACKGROUND: Peanut allergy is a common and severe phenotype of food allergy with
      a strong genetic component; HLA class II polymorphisms are attractive candidate
      genes for this disorder. OBJECTIVE: To determine possible genotypic associations
      of HLA class II with peanut allergy and attempt replication of previously
      reported associations. METHODS: Sibling pairs discordant for peanut allergy were
      genotyped (low resolution) by polymerase chain reaction-based methods to 7 DQ and
      18 DR allele groups. A chi2 analysis was undertaken against sibling controls with
      statistical adjustment for multiple analyses. RESULTS: Seventy-three children
      with confirmed peanut allergy (mean age, 6.5 years; male, 72%; asthma, 58%;
      atopic dermatitis, 62%; allergic rhinitis, 67%; other food allergies, 41%) and 75
      of their siblings who eat peanut (mean age, 8 years; male, 52%; asthma, 12%;
      atopic dermatitis, 22%; allergic rhinitis, 37%; other food allergy, 7%) were
      genotyped. Distribution of DQ7 (29% of children with peanut allergy vs 47%
      sibling controls) was statistically significantly different (P = .04) before
      statistical correction for multiple comparisons was made by multiplying them by
      the number of alleles tested (and not statistically significant after correction;
      P = .30). Distribution of DR11 was nearly statistically significant without
      statistical adjustment (26% with peanut allergy vs 41% of sibling controls; P =
      .07; corrected P = 1.3). Alleles that were previously reported to have a weak
      association with peanut allergy (DRB1 *03, *08; DQB1 *0302, *04) were not
      verified in this cohort (unadjusted P > .44). CONCLUSIONS: We could not establish
      an association between the HLA class II alleles evaluated in this cohort of
      sibling pairs discordant for peanut allergy.

PMID- 16802777
TI  - Anaphylaxis to Cyphomandra betacea Sendth (tamarillo) in an obeche wood
      (Triplochiton scleroxylon)--allergic patient.
AB  - BACKGROUND: Anaphylaxis after the first exposure to a food allergen is uncommon
      unless a cross-reaction is present. OBJECTIVE: To investigate a possible
      relationship between the fruit Cyphomandra betacea Sendth (commonly known as
      tamarillo) and the wood of Triplochiton scleroxylon (obeche) in a patient with
      allergic occupational bronchial asthma due to obeche wood who began to experience
      anaphylaxis episodes after eating tamarillo. METHODS: A 33-year-old carpenter
      exposed to obeche wood in his occupation was initially seen with rhinitis and
      bronchial asthma. The causal relationship of these symptoms to obeche wood
      exposure was investigated by means of peak flow monitoring and bronchial
      inhalation testing. Furthermore, the patient had 2 acute episodes of anaphylaxis
      a few minutes after eating salad containing tamarillo. He had never tasted
      tamarillo before. The allergologic study included skin prick tests, serum
      specific IgE determinations, bronchial challenges, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and immunoblotting. RESULTS: Results of skin
      prick tests with common aeroallergens were negative. Strong skin prick test
      responses were obtained with obeche and tamarillo. Results of bronchial challenge
      testing with obeche extract were positive. In tamarillo extract, a 28-kDa band
      appeared as the most relevant IgE-binding antigen. A similar band of 28 kDa
      happens to be frequently detected in obeche-allergic patients. CONCLUSION: To our
      knowledge, this is the first reported case of anaphylaxis to tamarillo presented
      in a patient allergic to obeche, which raises the question of a new cross
      reactivity antigen.

PMID- 16802778
TI  - Contemporaneous occurrence of allergic bronchopulmonary aspergillosis, allergic
      Aspergillus sinusitis, and aspergilloma.
AB  - BACKGROUND: The clinical categories of Aspergillus-related respiratory disorders
      usually remain mutually exclusive. The coexistence of allergic bronchopulmonary
      aspergillosis (ABPA) with aspergilloma is uncommon, whereas concurrent ABPA and
      allergic Aspergillus sinusitis (AAS) is rare. The association of these 3 clinical
      entities has previously been documented only once in a patient who had earlier
      been operated on for an aspergilloma before the diagnoses of ABPA and AAS were
      established. OBJECTIVE: To describe an adult in whom ABPA, AAS, and aspergilloma
      were diagnosed simultaneously. METHODS: Spirometry, radiography, computed
      tomography, skin allergy testing with Aspergillus antigens, serum precipitins
      against Aspergillus, total and specific IgE, functional endoscopic sinus surgery,
      and fungal culture were performed. RESULTS: A 26-year-old man who had asthma and
      rhinitis since childhood presented with hemoptysis. Serial chest radiographs
      revealed transient pulmonary infiltrates and an aspergilloma. Computed tomography
      of the thorax confirmed the aspergilloma and showed bilateral central
      bronchiectasis along with patchy infiltrates. Strong bands of precipitins were
      detected against Aspergillus fumigatus, and intradermal testing with Aspergillus
      antigens elicited strong type I and III hypersensitivity reactions. Specific IgE
      and IgG antibodies against A fumigatus were positive, and total IgE levels were
      significantly elevated. Peripheral blood eosinophilia was also detected. Sinus
      involvement was confirmed on computed tomography, and pathologic material
      obtained by functional endoscopic sinus surgery demonstrated allergic mucin that
      contained fungal elements. In addition, A fumigatus was cultured. CONCLUSIONS:
      ABPA, AAS, and aspergilloma can occur simultaneously in the same patient.

PMID- 16802779
TI  - The use of patch formulation of tulobuterol, a long-acting beta2-adrenoreceptor
      agonist, in the treatment of severe pediatric asthma.

PMID- 16802780
TI  - Atomic-scale deformation in N-doped carbon nanotubes.
AB  - We present the N-doping induced atomic-scale structural deformation in N-doped
      carbon nanotubes by using density functional theory calculations. For
      substitutional N-doped nanotube clusters, the N dopant with an excess electron
      lone pair exhibits the high negative charge, and the homogeneously distributed
      dopants enlarge the tube diameter in both zigzag and armchair cases. On the other
      hand, in pyridine-like N-doped ones, the concentrated N atoms result in a
      positively curved graphene layer and, thus, can be responsible for tube wall
      roughness and the formation of interlinked structures.

PMID- 16802781
TI  - Cycloaddition reaction of 1,3-butadiene with a symmetric Si adatom pair on the
      Si(111)7x7 surface.
AB  - We first found experimentally a cycloaddition reaction of a molecule on a
      symmetry Si pair, 1,3-butadiene on the Si adatom pair of Si(111)7x7, while up to
      now only asymmetric Si pairs were reported to be involved in cycloaddition
      reactions on Si surfaces. As the symmetry of a Si pair is expected to influence
      significantly a cycloaddition product and a reaction pathway, the [4+2]-like
      cycloaddition product of 1,3-butadiene on the Si adatom pair is suggested to form
      through a concerted reaction pathway in comparison to a stepwise reaction
      pathway, which is favorable in the formation of the [4+2]-like cycloaddition
      product on the asymmetric Si pair (the Si adatom-restatom pair).

PMID- 16802782
TI  - 2'-hydroxyl proton positions in helical RNA from simultaneously measured
      heteronuclear scalar couplings and NOEs.
AB  - The 2'-hydroxyl group in RNA plays an important structural role; it defines
      hydration in the minor groove, impacts thermodynamic stability of RNA, and often
      participates in RNA catalysis. To better study this important functional group in
      RNA, we describe a constant-time HMQC-IPAP-NOESY 3D NMR experiment. It
      simultaneously yields highly resolved 13C-separated NOEs from ribose protons to
      the 2'OH proton, as well as E.COSY-type measurement of JC-OH couplings, thereby
      permitting a quantitative study of the orientation of the 2'OH proton in RNA. The
      observed NOE patterns indicate that the 2'OH bonds in A-form helical RNA are
      primarily oriented toward the base domain, as further supported by small (1.3 +/-
      0.7 Hz) 3JC1'-2'OH and relatively large (4.2 +/- 0.7 Hz) 3JC3'-2'OH couplings.
      The constant-time HMQC-IPAP-NOESY is suitable for measurement of interactions of
      rapidly exchanging protons in proteins and nucleic acids.

PMID- 16802783
TI  - Preparation, characterization, and substrate metabolism of gold-immobilized
      cytochrome P450 2C9.
AB  - The cytochrome P450 enzymes represent an important class of heme-containing
      enzymes. There is considerable interest in immobilizing these enzymes on a
      surface so that interactions between a single enzyme and other species can be
      studied with respect to electron transfer, homodimer or heterodimer interactions,
      or for construction of biological-based chips for standardizing cytochrome P450
      metabolism or for high-throughput screening of pharmaceutical agents. Previous
      studies have generally immobilized P450 enzymes in a matrix or on a surface.
      Here, we have attached CYP2C9 to gold substrates such that the resulting
      construct maintains the ability to bind and metabolize substrates in the presence
      of NADPH and cytochrome P450 reductase. The activity of these chips is directly
      dependent upon the linkers used to attach CYP2C9 and to the presence of key
      molecules in the active site during enzyme attachment. A novel method to detect
      substrate-enzyme binding, namely, superconducting quantum interference device
      (SQUID) magnetometry, was used to monitor the binding of substrates. Most
      significantly, conditions that allow measurable CYP2C9 metabolism to occur have
      been developed.

PMID- 16802784
TI  - Particle-particle interactions between layered double hydroxide nanoparticles.
AB  - Changes in chemical properties of nanoscale particles include quantum size
      effect, changes in the cell parameters and lattice symmetry, and surface and
      interface effects. In the case of layered double hydroxides (LDHs), surface and
      interface effects dominate for nanoparticles of MgAl LDHs. Using TEM micrographs
      of nanoparticle-sized LDHs, we have found that the increased number of surface
      atoms relative to the internal atoms increases the surface-to-surface
      interparticle attractions. As a result, nanosize LDH particles are able to form
      continuous oriented films that adhere well to a polar substrate.

PMID- 16802785
TI  - Multiplexed detection of protein cancer markers with biobarcoded nanoparticle
      probes.
AB  - We have developed the chemistry for preparing a universal probe and the
      appropriate nano- and microparticle labels that can be used to do highly
      selective multiplexed detection of three protein cancer markers at low-femtomolar
      concentration in buffer and serum media. The approach relies on a new multiplexed
      version of the biobarcode amplification method and offers new opportunities for
      studying multiple protein markers in a single sample. This could lead to new
      forms of disease diagnosis and monitoring disease recurrence in a variety of
      settings.

PMID- 16802786
TI  - Conjugated chromophore arrays with unusually large hole polaron delocalization
      lengths.
AB  - We report variable temperature X-band EPR spectroscopic data for the cation
      radical states of meso-to-meso ethyne-bridged (porphinato)zinc(II) (PZnn)
      oligomers. These [PZn2-PZn7]+ species span an average 18-75 A length scale and
      display peak-to-peak EPR line widths (DeltaBp-p) that diminish with conjugation
      length. Analysis of these EPR data show that PZnn+ structures possess the largest
      hole polaron delocalization lengths yet measured; experiments carried out over a
      4-298 K temperature domain demonstrate remarkably that the charge delocalization
      length remains invariant with temperature. These cation radical EPR data are well
      described by a stochastic, near barrierless, one-dimensional charge hopping model
      developed by Norris for N equivalent sites on a polymer chain, where the
      theoretical EPR line width is given by DeltaBp-p(N-mer) = (1/N1/2)DeltaBp
      p(monomer); PZnn+ oligomers are the first such systems to verify a Norris-type
      hole delocalization mechanism over a substantial ( approximately 75 A) length
      scale. Given the time scale of the EPR measurement, these data show that either
      (i) Franck-Condon effects are incapable of driving charge localization in [PZn2
      PZn7]+, resulting in cation radical wave functions which are globally delocalized
      over a spatial domain that is large with respect to established benchmarks for
      hole-doped conjugated materials, or (ii) polaron hopping rates in these oligomers
      exceed 107 s-1, even at 4 K. Finally, this study demonstrates that polymeric
      building blocks having low magnitude inner sphere reorganization energies enable
      the development of electronic materials having long polaron delocalization
      lengths.

PMID- 16802787
TI  - Synthesis of amphiphilic superparamagnetic ferrite/block copolymer hollow
      submicrospheres.
AB  - Self-assembly can be a powerful, but simple, synthetic method for the fabrication
      and surface modification of nanometer- to micrometer-sized hollow spheres. Here
      we report a facile route for preparation of submicrometer ferrite hollow spheres
      which are amphiphilic and superparamagnetic. This unique approach involves the
      formation of ferrite nanocrystals and the simultaneous self-assembly of
      nanocrystals and block copolymer PEO-PPO-PEO into hollow spheres. Furthermore,
      this approach is general for the preparation of a series of ferrite hollow
      spheres, including Fe3O4, Co1-xFe2+xO4, and Mn1-xFe2+xO4. Unlike conventional
      hollow spheres, which are either hydrophobic or hydrophilic, the products we
      obtained exhibit excellent dispersibility in both polar and nonpolar solvents.

PMID- 16802788
TI  - Oxide hemostatic activity.
AB  - The tunable in vitro blood clotting activity of high-surface-area hemostatic
      bioactive glass is evaluated by Thromboelastograph, a clinical instrument for
      quantifying changes in blood during coagulation. The hemostatic trends associated
      with hemostatic bioactive glass and a new preparation of spherical hemostatic
      bioactive glass, along with similar Si- and Ca-containing oxides, are described
      and related to Si:Ca ratios, Ca2+ availability and coordination environment,
      porosity, DeltaHHydration, and surface area. Hemostatic bioactive glass is a new
      material with an excellent efficacy for inducing hemostasis and is chemically
      distinct from the traditional bioglass employed for bone growth.

PMID- 16802789
TI  - Model compounds of ruthenium-alkene intermediates in olefin metathesis reactions.
AB  - The development of a model system to study ruthenium-olefin complexes relevant to
      the mechanism of olefin metathesis is reported. Upon addition of 1,2
      divinylbenzene to (H2IMes)(py2)(Cl)2Ru=CHPh (H2IMes = 1,3-dimesityl-4,5
      dihydroimidazol-2-ylidene), two ruthenium-olefin adducts are formed. On the basis
      of 1H NMR spectroscopy experiments and X-ray crystallographic analysis, these
      complexes are assigned as side-bound isomers in which the olefin and H2IMes
      ligands are coordinated cis to each other. The dynamic interconversion of these
      two ruthenium complexes was determined to have a barrier of 19.1 +/- 0.1
      kcal/mol.

PMID- 16802790
TI  - Radical trapping by gold chlorides forming organogold intermediates.
AB  - Organogold compounds arising from the trapping of carbon-centered radicals by
      gold chlorides (AuCl, AuCl3, and HAuCl4) and colloidal gold have been
      characterized by different spectroscopic techniques. Laser flash photolysis has
      provided kinetic evidence of the occurrence of radical trapping in the
      microsecond time scale, while theoretical calculations give the energetics of the
      elementary steps. The trapping of carbon radicals by gold species observed here
      may explain why the presence of radical initiators enhance dramatically the
      activity of gold catalysts for some reactions occurring through radical
      intermediates.

PMID- 16802791
TI  - Sn12(2-): stannaspherene.
AB  - Stannaspherene. The Sn122- cluster is discovered to be a highly stable and highly
      symmetric icosahedral cage bonded by four delocalized radial pi bonds and nine
      delocalized on-sphere sigma bonds from the 5p orbitals of the Sn atoms. It has a
      diameter of 6.1 A, with a large empty interior volume, and can host most
      transition metal atoms inside, giving rise to a large class of endohedral
      chemical building blocks for cluster-assembled nanomaterials.

PMID- 16802792
TI  - Charge flipping at work: a case of pseudosymmetry.
AB  - Charge flipping (CF) is an amazingly simple structure solution method that uses
      single-crystal X-ray diffraction data. It is truly ab initio, no preliminary
      information on atom types, chemical composition, or space group symmetry is
      required. The algorithm is iterative and alternates between real and reciprocal
      spaces. Its simplest version only changes (flips) the sign of the electron
      density below a threshold, while in reciprocal space, it prescribes the moduli of
      observed structure factors. In this communication, we apply the algorithm in
      practice. The selected example presents a whole range of difficulties: it is
      large, contains only light atoms, is noncentrosymmetric, and shows a particularly
      awkward pseudosymmetry. To solve it with any of the traditional methods requires
      many hours of computer time, followed by a day of expert's handwork to find
      missing and to remove spurious atoms. In contrast, the CF algorithm provides the
      complete structure in a few seconds and without human intervention. It is also
      remarkable that the success rate is 100%, that is, any starting point in the high
      dimensional phase space leads to the solution. The treatment of translational
      pseudosymmetry is obviously a favorable case. Similar resistant structures with
      pseudosymmetries or ambiguous space groups are the practical applications where
      the CF method could well complement standard software procedures.

PMID- 16802793
TI  - New mechanistic insights regarding Pd/Cu catalysts for the Sonogashira reaction:
      HRMAS NMR studies of silica-immobilized systems.
AB  - The title technique, high-resolution magic angle spinning NMR of suspensions,
      constitutes a powerful new tool for investigating the structures and mobilities
      of immobilized species and, thus, for optimizing heterobimetallic catalyst
      systems, such as the Sonogashira coupling of terminal alkynes and aryl halides.

PMID- 16802794
TI  - Dielectrophoresis field flow fractionation of single-walled carbon nanotubes.
AB  - We report a study on Dielectrophoresis Field Flow Fractionation of Single-Wall
      Carbon Nanotubes (SWNTs). SWNTs, individually suspended in 1% SDBS solution, were
      separated by type when they passed a dielectrophoresis field flow fractionation
      device where 1 MHz AC voltage was supplied and the field strength was well below
      1 V per mum. Furthermore, we uniquely observed enrichment of semiconductive SWNTs
      based on their band gap. In addition to Raman spectrum, UV-vis absorption and NIR
      fluorescence spectra were used for solution samples for characterization.

PMID- 16802795
TI  - Crystal structure, dissolution, and deposition of a 5 nm functionalized metal
      organic great rhombicuboctahedron.
AB  - A metal-organic great rhombicuboctahedron (termed MOP-18) was functionalized with
      extended alkyl chains and crystallized. It has 12 rigid square-shaped Cu2(CO2)4
      paddle-wheel building units and 24 5-dodecoxybenzene-1,3-dicarboxylate links. MOP
      18 is soluble in a variety of organic solvents, such as tetrahydrofuran,
      chloroform, and toluene, which enabled its assembly on graphite substrate and its
      observation by scanning tunneling microscopy.

PMID- 16802796
TI  - Optical sensing of parts per million levels of water in organic solvents using
      redox-active osmium chromophore-based monolayers.
AB  - Optical sensing of parts per million (ppm)-levels of H2O (10-300 ppm) in an
      organic solvent with robust, osmium chromophore-based monolayers is demonstrated.
      The H2O-induced reduction of the covalently bound osmium(III) complex is fully
      reversible and can be readily monitored by UV/vis absorption spectroscopy. The
      thermally robust sensor can be reactivated chemically within 3 min.

PMID- 16802797
TI  - Accounting for spin relaxation in quantitative pulse gradient spin echo NMR
      mixture analysis.
AB  - Pulsed gradient spin-echo (PGSE) NMR is intrinsically nonquantitative. Because
      the experiment is echo-based, differences in the relaxation behavior of the
      nuclei among the components give rise to varied intensities and lead to
      nonquantitative spectra. A method is presented that restores resolved,
      quantitative spectra from mixtures by processing data from several PGSE NMR
      experiments with varied delay times. The approach incorporates a simple data
      acquisition scheme and leads to a computationally fast, linear least-squares
      analysis. It is anticipated the method will be of much interest for performing
      mixture analysis of polymer solutions and the characterization of surface
      modified nanoparticulate dispersions.

PMID- 16802798
TI  - Toward a protecting-group-free halogen-metal exchange reaction: practical,
      chemoselective metalation of functionalized aromatic halides using dianion-type
      zincate, tBu4ZnLi2.
AB  - A versatile preparation method for aromatic zincate compounds through a halogen
      zinc exchange reaction using dilithium tetra-tert-butylzincate (tBu4ZnLi2) has
      been developed. This reagent permits efficient preparation of highly
      functionalized aromatic zincates, particularly, those with electrophilic
      functional groups, such as ester, amide, alcohol, and phenol. Halogen-zinc
      exchange reactions followed by electrophilic trapping (with allyl bromide or
      benzaldehyde) proved to be a powerful tool for C-C bond formation on
      functionalized aromatic rings. The functionalized aromatic zincate intermediate
      was also found to undergo copper- and palladium-catalyzed C-C bond-forming
      reactions with good yields and high chemoselectivity.

PMID- 16802799
TI  - Mapping allostery through equilibrium perturbation NMR spectroscopy.
AB  - The understanding of allostery relies on the comparative analysis of
      macromolecules in their free and bound states. However, the direct free versus
      bound comparison is often challenging due to the instability of one of the two
      forms. This problem is effectively circumvented by using minor free/bound
      equilibrium perturbations which are tolerated without compromising sample
      stability. The subtle equilibrium perturbations are still able to reveal
      significant apo/holo differences if monitored by NMR experiments that are
      sensitive to minor populations within dynamic equilibria, such as NMR relaxation
      dispersion (NMRD) and hydrogen exchange (H/D and H/H) rates. These measurements
      are complementary to each other as they unmask how a ligand affects both the
      stable and the excited states of the free energy landscape for its protein
      receptor. The proposed equilibrium perturbation approach therefore significantly
      expands the scope of applicability of NMRD and hydrogen exchange experiments to
      the investigation of ligand-protein interactions, in general, unveiling
      allosteric "hot spot" maps for systems that have been traditionally elusive to
      direct free/bound comparisons.

PMID- 16802800
TI  - Magnetic field effects and radical pair mechanisms in enzymes: a reappraisal of
      the horseradish peroxidase system.
AB  - Reinvestigation by stopped-flow spectrophotometry of the previously observed
      influence of a static magnetic field on the horseradish peroxidase (HRP)
      catalyzed reduction of hydrogen peroxide by Taraban et al. (J. Am. Chem. Soc.
      1997, 119, 5768) did not reproduce the originally observed effects. No magnetic
      field effect was observed for static fields of up to 75 mT. Field-induced changes
      in both k1 and k2 reported in the original work were found to produce equal and
      opposite effects on the shape of the observed kinetic decay of the 418 nm
      spectroscopic signal as a result of the difference in the relative absorbances of
      Native HRP and Compound II.

PMID- 16802801
TI  - C-C bond-forming reductive elimination from a zirconium(IV) redox-active ligand
      complex.
AB  - Carbon-carbon bond-forming reductive elimination of biphenyl is observed upon two
      electron oxidation of the [ZrIVPh2(ap)2]2- dianion. Crossover experiments confirm
      that the C-C bond-forming step occurs at a single zirconium metal center. The
      reactivity is enabled by the participation of a redox-active amidophenolate
      ligand set.

PMID- 16802802
TI  - 2-azaadamantane N-oxyl (AZADO) and 1-Me-AZADO: highly efficient organocatalysts
      for oxidation of alcohols.
AB  - Development of a stable nitroxyl radical class of catalysts, 2-azaadamantane N
      oxyl (AZADO) and 1-Me-AZADO, for highly efficient oxidation of alcohols is
      described. AZADO and 1-Me-AZADO exhibit superior catalytic proficiency to TEMPO,
      converting various sterically hindered alcohols to the corresponding carbonyl
      compounds in excellent yields.

PMID- 16802803
TI  - A highly efficient preparative method of alpha-ylidene-beta-diketones via Au(III)
      catalyzed acyl migration of propargylic esters.
AB  - A highly efficient synthesis of alpha-alkylidene or benzylidene-beta-diketones
      from readily available propargylic esters has been developed. The proposed key
      transformation is a novel intramolecular acyl migration to nucleophilic AuIII
      C(sp2) bonds. Noteworthy features of this method are its efficiency and
      stereoselectivity. The yields of this reaction were mostly close to quantitative,
      and high to excellent stereoselectivities were observed in the cases of dienyl
      beta-diketones.

PMID- 16802804
TI  - Copper-catalyzed asymmetric conjugate addition of Grignard reagents to
      trisubstituted enones. Construction of all-carbon quaternary chiral centers.
AB  - The copper-catalyzed asymmetric conjugate addition of Grignard reagents to
      trisubstituted cyclic enones affords enantioenriched all-carbon quaternary
      centers with up to 96% ee. The chiral ligand is a diaminocarbene, directly
      generated in situ. The combination of Grignard reagent and diaminocarbene is
      unprecedented in conjugate addition, and the additon of the phenyl group, on such
      enones, cannot be done by other conjugate addition methods.

PMID- 16802805
TI  - Highly enantioselective azadiene Diels-Alder reactions catalyzed by chiral N
      heterocyclic carbenes.
AB  - Highly enantioselective, N-heterocyclic carbene (NHC)-catalyzed aza-Diels-Alder
      reactions are described. A novel chiral triazolium salt based on the cis-1,2
      aminoindanol platform serves as an efficient precatalyst for the NHC-catalyzed
      redox generation of enolate dienophiles that undergo LUMOdiene-controlled Diels
      Alder reactions with N-sulfonyl-alpha,beta-unsaturated imines in good yields and
      with exceptional diastereo- and enantioselectivities (>99% ee). In contrast to
      uncatalyzed variants, this organocatalytic process proceeds at room temperature
      without stoichiometric reagents, producing synthetically valuable,
      enantiomerically pure cis-3,4-disubstituted dihydropyridinone products.

PMID- 16802806
TI  - Unveiling the "booster effect" of fluorinated alcohol solvents: aggregation
      induced conformational changes and cooperatively enhanced H-bonding.
AB  - The influence of conformation and aggregation on the hydrogen bond donor ability
      of fluorinated alcohol solvents [1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 1
      phenyl-2,2,2-trifluoroethanol (PhTFE)] was explored theoretically (DFT) and
      experimentally (NMR, kinetics, crystal structure analyses). The detailed DFT
      analysis revealed a pronounced dependence of the H-bond donor ability on the
      conformation along the CO-bond of the monomeric alcohols. The donor orbital
      energy (sigma*(OH)) decreases and the molecular dipole moment (mu) increases
      drastically from the antiperiplanar (ap) to the synperiplanar (sp) H(C)COH
      conformation. The kinetics of olefin epoxidation with H(2)O(2) in HFIP indicate
      higher order solvent aggregates (2-3 monomers) to be responsible for the
      activation of the oxidant. Single-crystal X-ray analyses of HFIP and PhTFE
      confirmed the existence of H-bonded aggregates (infinite helices, ribbons, and
      cyclic oligomers) and the predominance of sc to sp conformations of the
      fluoroalcohol monomers. These aggregate structures served as the basis for a DFT
      analysis of the H-bond donor ability at the terminal hydroxyl group of HFIP mono-
      to pentamers. Both the LUMO energy and the natural charge of the terminal
      hydroxyl proton indicated a substantial cooperative influence of dimerization and
      trimerization on the H-bond donor ability. We therefore conclude that dimers and
      trimers, with the individual monomers in their sc to sp conformation, play a
      crucial role for the solvolytic and catalytic effects exerted by HFIP, rather
      than monomers.

PMID- 16802808
TI  - Electronic properties of furyl substituents at phosphorus and their influence on
      31P NMR chemical shifts.
AB  - The electronic properties of 2-furyl and 3-furyl substituents attached to
      phosphanes and phosphonium salts were studied by means of IR spectroscopy and
      experimental and computational (31)P NMR spectroscopy. The heteroaromatic systems
      proved to be electron withdrawing with respect to phenyl substituents. However,
      phosphorus atoms with attached furyl substituents are strongly shielded in NMR.
      The reason for this phenomenon was studied by solid state (31)P MAS NMR
      experiments. The chemical shift tensor was extracted, and the orientation within
      the molecules was determined. The tensor component sigma(33), which is effected
      the most by furyl systems, is oriented perpendicular to the P-C bonds of the
      substituents. P-furyl bonds are shorter than P-phenyl bonds. We assume therefore
      a lower ground-state energy of the molecules, because of the electron withdrawing
      properties of the 2-furyl systems. The sigma(para) component of the (31)P NMR
      magnetic shielding is therefore smaller, which results in an overall increase of
      the magnetic shielding.

PMID- 16802807
TI  - Charging behavior of single-stranded DNA polyelectrolyte brushes.
AB  - DNA monolayers are widely used in fundamental and applied genomics and are
      versatile experimental models for elucidating the behavior of charged polymers at
      interfaces. The physical behavior of these systems is to a large extent governed
      by their internal ionic microenvironment, which is investigated here for layers
      of end-tethered, single-stranded DNA oligonucleotides (DNA brushes). Retention of
      counterions by the DNA brush manifests as lowered susceptibility of the
      interfacial capacitance to external salt conditions. A physical model based on
      concepts adapted from polymer science was used to further elucidate the
      connection between monolayer organization and its charging behavior. The data
      indicate a reorganization of the monolayer with changes in ionic strength and
      strand coverage that is consistent with that expected for a polyelectrolyte
      brush. A method for electrochemical quantification of strand coverage, based on
      shift of reduction potential for redox counterions associated with the DNA
      monolayer, is also described. These results provide guidance for development of
      label-free electrochemical diagnostics employing DNA monolayers and formulate a
      description of monolayer behavior within a polymer science framework.

PMID- 16802809
TI  - Abundant polymorphism in a system with multiple hydrogen-bonding opportunities:
      oxalyl dihydrazide.
AB  - To date, only one crystal structure has been reported in the literature for
      oxalyl dihydrazide [H(2)N.NH.CO.CO.NH.NH(2)]. In the present paper, we report the
      discovery of four new polymorphs of oxalyl dihydrazide, obtained by
      crystallization from solution under different conditions, including the use of
      different crystallization solvents. All polymorphs have the trans-trans-trans
      conformation of the N-N-C-C-N-N backbone, but the positions of the hydrogen atoms
      of the NH(2) groups relative to this backbone differ between the different
      polymorphs through variation of the torsion angle around each NH-NH(2) bond. The
      different polymorphs display a range of different hydrogen-bonding arrangements,
      constructed from different types of hydrogen-bonded array. The existence of
      several different potential hydrogen-bond donor and hydrogen-bond acceptor groups
      in the oxalyl dihydrazide molecule, together with the fact that the N-H bonds of
      the NH(2) groups adopt different orientations with respect to the molecular
      plane, leads to several possible geometric permutations for hydrogen-bonding
      arrangements in the solid state. It would not be surprising if even more
      polymorphs of oxalyl dihydrazide are discovered in the future.

PMID- 16802810
TI  - Tremendous spin-splitting effects in open boron nitride nanotubes: application to
      nanoscale spintronic devices.
AB  - Our calculations demonstrate that the intrinsic magnetism of boron nitride
      nanotubes (BNNTs) can be induced by their open ends, and the resulting magnetic
      moment is sensitive to the chirality of BNNTs. It is found that BNNTs, a pure sp
      electron system, present a tremendous spin-splitting larger than 1 eV and that B
      rich-ended and N-rich-ended BNNTs exhibit "conjugate", spin-polarized, deep-gap
      states. Tremendous spin-splitting effects combined with considerable local spin
      polarizations at the open ends make BNNTs significant for applications of
      nanoscale spintronics such as spin-polarized electron emitters.

PMID- 16802811
TI  - Discovery of glutathione S-transferase inhibitors using dynamic combinatorial
      chemistry.
AB  - Protein-directed dynamic combinatorial chemistry (DCC) relies on reversible
      chemical reactions that can function under the near-physiological conditions
      required by the biological target. Few classes of reaction have so far proven
      effective at generating dynamic combinatorial libraries (DCLs) under such
      constraints. In this study, we establish the conjugate addition of thiols to
      enones as a reaction well-suited for the synthesis of dynamic combinatorial
      libraries (DCLs) directed by the active site of the enzyme glutathione S
      transferase (GST). The reaction is fast, freely reversible at basic pH, and
      easily interfaced with the protein, which is a target for the design of
      inhibitors in cancer therapy and the treatment of parasitic diseases such as
      schistosomiasis. We have synthesized DCLs based on glutathione (GSH, 1) and the
      enone ethacrynic acid, 2a. By varying either set of components, we can choose to
      probe either the GSH binding region ("G site") or the adjacent hydrophobic
      acceptor binding region ("H site") of the GST active site. In both cases the
      strongest binding DCL components are identified due to molecular amplification by
      GST which, in the latter system, leads to the identification of two new
      inhibitors for the GST enzyme.

PMID- 16802812
TI  - Unexpected four-membered over six-membered ring formation during the synthesis of
      azaheterocyclic phosphonates: experimental and theoretical evaluation.
AB  - The cyclization of functionalized aminophosphonates is studied on both
      experimental and theoretical grounds. In a recently described route to phosphono
      beta-lactams [Stevens C. V.; Vekemans, W.; Moonen, K.; Rammeloo, T. Tetrahedron
      Lett. 2003, 44, 1619], it was found that starting from an ambident allylic anion
      only four-membered rings were formed without any trace of six-membered lactams.
      New anion trapping experiments revealed that the gamma-anion is highly reactive
      in intermolecular reactions. Ab initio calculations predict higher reaction
      barriers for the gamma-anion due to restricted rotation about the C-N bond and
      due to highly strained transition states during ring closure. The sodium or
      lithium counterion, explicit dimethyl ether solvent molecules, and bulk solvent
      effects were properly taken into account at various levels of theory.

PMID- 16802813
TI  - Replacement of a proline with silaproline causes a 20-fold increase in the
      cellular uptake of a Pro-rich peptide.
AB  - The results presented here show that elementary design enhancements have led to a
      20-fold increase in the cellular uptake properties of a Pro-rich cell-penetrating
      peptide. These results are relevant not only due to the increasing interest in
      using CPPs as molecular shuttles for intracellular drug delivery but also because
      they illustrate the power of combining conformational analysis with rational
      design to modulate the behavior of biologically active compounds.

PMID- 16802814
TI  - PNA/dsDNA complexes: site specific binding and dsDNA biosensor applications.
AB  - The ability of peptide nucleic acids (PNA) to form specific higher-order (i.e.,
      three- and four-stranded) complexes with DNA makes it an ideal structural probe
      for designing strand-specific dsDNA biosensors. Higher-order complexes are formed
      between a dye-labeled charge-neutral PNA probe and complementary dsDNA. Addition
      of a light-harvesting cationic conjugated polymer (CCP) yields supramolecular
      structures held together by electrostatic forces that incorporate the CCP and the
      dye-labeled PNA/DNA complexes. Optimization of optical properties allows for
      excitation of the CCP and subsequent fluorescence resonance energy transfer
      (FRET) to the PNA-bound dye. In the case of noncomplementary dsDNA, complexation
      between the probe and target does not occur, and dye emission is weak. The
      binding between PNA and noncomplementary and complementary dsDNA was examined by
      several methods. Gel electrophoresis confirms specificity of binding and the
      formation of higher-order complexes. Nano-electrospray mass spectrometry gives
      insight into the stoichiometric composition, including PNA/DNA, PNA(2)/DNA,
      PNA/DNA(2), and PNA(2)/DNA(2) complexes. Finally, structural characteristics and
      binding-site specificity were examined using ion mobility mass spectrometry in
      conjunction with molecular dynamics. These results give possible conformations
      for each of the higher-order complexes formed and show exclusive binding of PNA
      to the complementary stretch of DNA for all PNA/DNA complexes. Overall, the
      capability and specificity of binding indicates that the CCP/PNA assay is a
      feasible detection method for dsDNA and eliminates the need for thermal
      denaturing steps typically required for DNA hybridization probe assays.

PMID- 16802815
TI  - Coverage dependent supramolecular structures: C60:ACA monolayers on Ag(111).
AB  - The dependence of supramolecular structure on fractional molecular coverage has
      been investigated for acridine-9-carboxylic acid (ACA) and the C(60):ACA binary
      molecular system. The coverage-dependent phase diagram for ACA is first
      determined from room-temperature STM imaging. At low molecular coverages (theta <
      0.4 ML, ML = monolayer), ACA forms a 2-D gas phase. Ordered ACA structures appear
      with increasing coverage: first a chain structure composed of ACA molecules
      linked by consecutive O-H...N hydrogen bonds (theta > 0.4 ML), then a dimer
      structure composed of ACA dimers linked by paired carboxyl-carboxyl hydrogen
      bonds (theta approximately equal to 1.0 ML). Structures of the C(60):ACA binary
      system depend on the coverage of predeposited ACA. At intermediate (0.4 ML
      approximately 0.8 ML) ACA coverages, C(60) deposition results in a hexagonal
      cooperative structure with the C(60) periodicity nearly 3 times that of the
      normal C(60) 2-D packing of 1 nm and exists in enantiopure domains. At higher ACA
      coverages, a C(60) quasi-chain structure is formed in which parallel C(60) chains
      are spaced by ACA dimer domains. The mechanistic role of the initial ACA phase in
      the formation of C(60):ACA supramolecular structures is described. Chemically
      intuitive molecular packing models are presented based on the observed STM
      images.

PMID- 16802816
TI  - An infrared nuNH scale for weakly basic anions. Implications for single-molecule
      acidity and superacidity.
AB  - The N-H stretching frequencies of tri-n-octylammonium salts are reported for a
      series of weakly basic anions (A(-)), many of which are the conjugate bases of
      known strong acids and superacids. Data have been collected primarily in carbon
      tetrachloride, where Oct(3)N(+)-H...A(-) contact ion pairs are formed. In the
      more polar solvent 1,2-dichloroethane, some salts form both contact and solvent
      separated ion pairs. Salts have also been studied in crystalline form or as oils.
      In general, the nuNH frequencies decrease in the order fluoroanions > carboranes
      > oxyanions, reflecting the relative basicities of the anions. By inference, the
      data reflect differences in the acidity of the corresponding conjugate acids
      (HA). This qualitative indicator of acid strength is useful because it reflects
      acidity on an individual molecule basis rather than in bulk. In this respect, it
      provides a condensed-phase analogy to gas-phase ("intrinsic") acidity and gives
      insight into the aggregation phenomena that determine bulk acidity. The data also
      reveal the importance of the chemical stability of conjugate base anions in
      attaining high acidity and suggest where acids stronger than those presently
      known may be discovered.

PMID- 16802817
TI  - Cobalt-mediated cyclic and linear 2:1 cooligomerization of alkynes with alkenes:
      a DFT study.
AB  - The mechanism of the cobalt-mediated [2 + 2 + 2] cycloaddition of two alkynes to
      one alkene to give CpCo-complexed 1,3-cyclohexadienes (cyclic oligomerization)
      has been studied by means of DFT computations. In contrast to the mechanism of
      alkyne cyclotrimerization, in which final alkyne inclusion into the common
      cobaltacyclopentadiene features a direct "collapse" pathway to the complexed
      arene, alkene incorporation proceeds via insertion into a Co-C sigma-bond rather
      than inter- or intramolecular [4 + 2] cycloaddition. The resulting seven-membered
      metallacycle 7 is a key intermediate which leads to either CpCo-complexed
      cyclohexadiene 5 or hexatriene 13. The latter transformation, particularly
      favorable for ethene, accounts, in part, for the linear oligomerization observed
      occasionally in these reactions. With aromatic double bonds, a C-H activation
      mechanism by the cobaltacyclopentadiene seems more advantageous in hexatriene
      product formation. Detailed investigations of high- and low-spin potential energy
      surfaces are presented. The reactivity of triplet cobalt species was found
      kinetically disfavored over that of their singlet counterparts. Moreover, it
      could not account for the formation of CpCo-complexed hexatrienes. However,
      triplet cobalt complexes cannot be ruled out since all unsaturated species
      appearing in this study were found to exhibit triplet ground states.
      Consequently, a reaction pathway that involves a mixing of both spin-state energy
      surfaces is also described (two-state reactivity). Support for such a pathway
      comes from the location of several low-lying minimum-energy crossing points
      (MECPs) of the two surfaces.

PMID- 16802818
TI  - pH-induced hysteretic gating of track-etched polycarbonate membranes:
      swelling/deswelling behavior of polyelectrolyte multilayers in confined geometry.
AB  - pH-induced hysteretic gating of track-etched polycarbonate membranes (TEPC) has
      been achieved by depositing layer-by-layer assembled polyelectrolyte multilayers
      comprising poly(allylamine hydrochloride) (PAH) and poly(sodium 4
      styrenesulfonate) (PSS) at a high pH condition (pH > 9.0). Scanning electron
      microscopy and transmission electron microscopy showed that the average bilayer
      thickness of multilayers was greater within the cylindrical pores of track-etched
      polycarbonate membranes compared to the multilayers on planar substrates (e.g.,
      Si wafers and the face of TEPC membranes). Swelling/deswelling properties of
      multilayers and gating properties of the multilayer-modified TEPC membranes were
      studied by measuring the flux of pH-adjusted deionized water. Large discontinuous
      changes in the transmembrane flux were observed, indicating that the multilayers
      within the cylindrical pores of TEPC membranes exhibit the discontinuous
      swelling/deswelling behavior observed previously for planar systems. The degree
      of swelling as estimated by simple models, however, showed that (PAH/PSS)
      multilayers in the confined geometry swelled to smaller extents compared to the
      same multilayers on planar substrates under the same conditions. Multilayer
      modified membranes showed reversible gating properties as the pH condition of
      feed solution was alternated between pH 2.5 and 10.5. In situ atomic force
      microscopy (AFM) was used to visualize the closing of the pores as a function of
      time. The hysteretic gating property of the multilayer-modified TEPC membrane was
      utilized to achieve either a "closed" or "open" state at one pH condition
      depending on the pretreatment history, thereby enabling either the retention or
      passage of high-molecular weight polymers by varying the membrane pretreatment
      condition.

PMID- 16802819
TI  - Structural chemistry and metamagnetism of an homologous series of layered
      manganese oxysulfides.
AB  - An homologous series of layered oxysulfides Sr2MnO2Cu(2m-delta)S(m+1) with
      metamagnetic properties is described. Sr2MnO2Cu(2-delta)S2 (m = 1), Sr2MnO2Cu(4
      delta)S3 (m = 2) and Sr2MnO2Cu(6-delta)S4 (m = 3), consist of MnO2 sheets
      separated from antifluorite-type copper sulfide layers of variable thickness by
      Sr(2+) ions. All three compounds show substantial and similar copper deficiencies
      (delta approximately equal to 0.5) in the copper sulfide layers, and single
      crystal X-ray and powder neutron diffraction measurements show that the copper
      ions in the m = 2 and m = 3 compounds are crystallographically disordered,
      consistent with the possibility of high two-dimensional copper ion mobility.
      Magnetic susceptibility measurements show high-temperature Curie-Weiss behavior
      with magnetic moments consistent with high spin manganese ions which have been
      oxidized to the (2+delta)+ state in order to maintain a full Cu-3d/S-3p valence
      band, and the compounds are correspondingly p-type semiconductors with
      resistivities around 25 Omega cm at 295 K. Positive Weiss temperatures indicate
      net ferromagnetic interactions between moments. Accordingly, magnetic
      susceptibility measurements and low-temperature powder neutron diffraction
      measurements show that the moments within a MnO(2) sheet couple ferromagnetically
      and that weaker antiferromagnetic coupling between sheets leads to A-type
      antiferromagnets in zero applied magnetic field. Sr2MnO2Cu(5.5)S4 and
      Sr2MnO2Cu(3.5)S3 are metamagnets which may be driven into the fully ordered
      ferromagnetic state below 25 K by the application of fields of 0.06 and 1.3 T
      respectively. The relationships between the compositions, structures, and
      physical properties of these compounds, and the prospects for chemical control of
      the properties, are discussed.

PMID- 16802820
TI  - Mimicking cAMP-dependent allosteric control of protein kinase A through
      mechanical tension.
AB  - We report the activation of an enzyme complex by mechanical tension. Protein
      kinase A, a tetrameric enzyme that, in the cell, is allosterically controlled by
      cAMP, has been modified by the insertion of a "molecular spring" on the
      regulatory subunit. The spring is made of DNA, and its stiffness can be varied
      externally by hybridization to a complementary strand. This allows us to exert a
      controlled mechanical tension between the two points on the protein's surface
      where the spring is attached. We show that upon applying the tension, we can
      activate the enzyme with efficiency comparable to the activation by its natural
      regulatory molecule, cAMP.

PMID- 16802821
TI  - High triplet energy polymer as host for electrophosphorescence with high
      efficiency.
AB  - We report the conjugated polymer P(tBu-CBP) as a host with high triplet energy
      (E(T) 2.53 eV) and suitable HOMO (5.3 eV) and LUMO (2.04 eV) energy levels. Upon
      doping with green and red emission Ir-complexes, it gives devices with high
      luminous and external quantum efficiencies for green emission (23.7 cd/A, 6.57%)
      and for red emission (5.1 cd/A, 4.23%), respectively, and low turn-on voltage (3
      V). For both devices, the efficiencies are higher than those of the corresponding
      devices with the same backbone P(3,6-Cz) as a host by a factor of 4, even though
      the latter has an E(T) (2.6 eV) slightly higher than that of the former. The
      results reflect that, in phosphorescent devices, the difference in E(T) between
      the host and guest is not the only factor that determines the device efficiency,
      and the present side group modification via the 9 position of carbazole also
      plays an important role, which allows a tuning of HOMO and LUMO levels to provide
      more balance in electron and hole fluxes and provides prevention from formation
      of excimer.

PMID- 16802822
TI  - Regio- and stereoselective nickel-catalyzed homoallylation of aldehydes with 1,3
      dienes.
AB  - Ni(acac)(2) catalyzes homoallylation of aldehydes with 1,3-dienes in the presence
      of triethylborane. Triethylborane serves as a reducing agent delivering a formal
      hydride to the C2 position of 1,3-dienes, thus generating a formal homoallyl
      anion species and enabling the novel homoallylation of aldehydes. The reaction
      proceeds smoothly at room temperature in the absence of any phosphane or nitrogen
      ligands and is highly regioselective and stereoselective for a wide variety
      combination of aldehydes and 1,3-dienes: e.g., isoprene and benzaldehyde combine
      to give a mixture of anti- and syn-1-phenyl-3-methyl-4-penten-1-ol (2.2) in a
      ratio of 15:1 in 90% yield. Under the conditions, sterically congested aliphatic
      aldehydes and ketones show low yields. In such cases, diethylzinc serves as a
      substitute for triethylborane and yields the expected products in good yields
      with similarly high regio- and stereoselectivity. 1,3-Cyclohexadiene is one
      exception among 24 kinds of dienes examined and undergoes allylation (not
      homoallylation) selectively.

PMID- 16802823
TI  - Structural factors controlling the self-assembly of columnar liquid crystals.
AB  - A series of disc-shaped molecules were prepared by the condensation of 1,2
      diamines with 2,3,6,7-tetrakis(hexyloxy)phenanthrene-9,10-dione to investigate
      the relationship between changes in molecular structure and the self-assembly of
      columnar liquid crystalline phases. A comparison of compounds with different core
      sizes indicated that molecules with larger aromatic cores had a greater
      propensity to form columnar phases, as did compounds substituted with electron
      withdrawing groups. In contrast, molecules with electron-donating substituents
      were nonmesogenic. The clearing temperature of columnar phases increased linearly
      with the electron-withdrawing ability of the substituents, as quantified by
      Hammett sigma-values. The observed trends can be rationalized in terms of the
      strength of pi-pi interactions between aromatic cores in the liquid crystalline
      phases and suggest that both electrostatic interactions and dispersion forces
      play important roles in the self-assembly of these materials.

PMID- 16802824
TI  - Sequence-specific detection of femtomolar DNA via a chronocoulometric DNA sensor
      (CDS): effects of nanoparticle-mediated amplification and nanoscale control of
      DNA assembly at electrodes.
AB  - We herein report a novel nanoparticle-based electrochemical DNA detection
      approach. This DNA sensor is based on a "sandwich" detection strategy, which
      involves capture probe DNA immobilized on gold electrodes and reporter probe DNA
      labeled with gold nanoparticles that flank the target DNA sequence.
      Electrochemical signals are generated by chronocoulometric interrogation of
      [Ru(NH(3))(6)](3+) that quantitatively binds to surface-confined capture probe
      DNA via electrostatic interactions. We demonstrated that the incorporation of a
      gold nanoparticle in this sensor design significantly enhanced the sensitivity
      and the selectivity. Nanoscale control of the self-assembly process of DNA probes
      at gold electrodes further increased the sensor performance. As a result of these
      two combined effects, this DNA sensor could detect as low as femtomolar
      (zeptomoles) DNA targets and exhibited excellent selectivity against even a
      single-base mismatch. In addition, this novel DNA sensor showed fairly good
      reproducibility, stability, and reusability.

PMID- 16802825
TI  - Structure and enhanced reactivity rates of the D5h Sc3N@C80 and Lu3N@C80
      metallofullerene isomers: the importance of the pyracylene motif.
AB  - In this paper we report enhanced reactivity of the D(5h) isomers in comparison
      with the more common I(h) isomers of Sc(3)N@C(80) and Lu(3)N@C(80) toward Diels
      Alder and 1,3-dipolar tritylazomethine ylide cycloaddition reactions. Also, the
      structure of the D(5h) isomer of Sc(3)N@C(80) has been determined through single
      crystal X-ray diffraction on D(5h)-Sc(3)N@C(80).Ni(OEP).2benzene (OEP =
      octaethylporphyrin). The Sc(3)N portion of D(5h)-Sc(3)N@C(80) is strictly planar,
      but the plane of these four atoms is tipped out of the noncrystallographic,
      horizontal mirror plane of the fullerene by 30 degrees . The combination of short
      bond length and high degree of pyramidization for the central carbon atoms of the
      pyracylene sites situated along a belt that is perpendicular to the C(5) axis
      suggests that these are the sites of greatest reactivity in the D(5h) isomer of
      Sc(3)N@C(80). Consistent with the observation of higher reactivity observed for
      the D(5h) isomers, cyclic voltammetry and molecular orbital (MO) calculations
      demonstrate that the D(5h) isomers have slightly smaller energy gaps than those
      of the I(h) isomers. The first mono- and bis-adducts of D(5h) Sc(3)N@C(80) have
      been synthesized via 1,3-dipolar cycloaddition of tritylazomethine ylide. The NMR
      spectrum for the monoadduct 2b is consistent with reaction at the 6,6-ring
      juncture in the pyracylene unit of the D(5h) Sc(3)N@C(80) cage and is the
      thermodynamically stable isomer. On the other hand, monoadduct 2a undergoes
      thermal conversion to other isomeric monoadducts, and three possible structures
      are proposed.

PMID- 16802826
TI  - Two-state reactivity in alkane hydroxylation by non-heme iron-oxo complexes.
AB  - Density functional theory is used to explore the mechanisms of alkane
      hydroxylation for four synthetic non-heme iron(IV)-oxo complexes with three
      target substrates (Kaizer, J.; Klinker, E. J.; Oh, N. Y.; Rohde; J.-U.; Song, W.
      J.; Stubna, A.; Kim, J.; Munck, E.; Nam, W.; Que, L., Jr. J. Am. Chem. Soc. 2004,
      126, 472-473; Rohde, J.-U.; Que, L., Jr. Angew. Chem. Int. Ed. 2005, 44, 2255
      2258.). The iron-oxo reagents possess triplet ground states and low-lying quintet
      excited states. The set of experimental and theoretical reactivity trends can be
      understood if the reactions proceed on the two spin states, namely two-state
      reactivity (TSR); an appropriate new model is presented. The TSR model makes
      testable predictions: (a) If crossing to the quintet state occurs, the
      hydroxylation will be effectively concerted; however, if the process transpires
      only on the triplet surface, stepwise hydroxylation will occur, and side products
      derived from radical intermediates would be observed (e.g., loss of
      stereochemistry). (b) In cases of crossing en route to the quintet transition
      state, one expects kinetic isotope effects (KIEs) typical of tunneling. (c) In
      situations where the two surfaces contribute to the rate, one expects
      intermediate KIEs and radical scrambling patterns that reflect the two processes.
      (d) Solvent effects on these reactions are expected to be very large.

PMID- 16802827
TI  - Chloride selective calix[4]arene optical sensor combining urea functionality with
      pyrene excimer transduction.
AB  - A neutral 2-site chloride selective compound has been developed (3), based on a
      1,3-alternate tetrasubstituted calix[4]arene providing a preorganized
      supramolecular scaffold. The resultant supramolecular cavity is among the first
      to combine urea functional groups bridged with single methylene spacers to pyrene
      moieties. It combines a naturally and synthetically proven H-bonding system with
      the elegant ratiometric fluorescent signaling properties of an intramolecular
      pyrene excimer system, triggered by conformational changes upon anion
      coordination. The excimer emission of 3 is quenched, with a simultaneous rise in
      the monomer emission solely by the chloride anion among a wide variety of anions
      tested. 3 has an association constant of 2.4 x 10(4) M(-1) with chloride. The
      suitability and advantages of ratiometric optical sensor compounds like 3 for use
      in practical sensor devices is discussed. 3 has an LOD of 8 x 10(-6) M with
      chloride in acetonitrile-chloroform (95:5 v/v). A dynamic fluorescence study
      revealed a response time of < 3 s. A recently developed and simple HPLC-based
      purification method complimented conventional organic work up methods to yield
      pure product.

PMID- 16802828
TI  - Optimization of bivalent glutathione S-transferase inhibitors by combinatorial
      linker design.
AB  - Dimeric glutathione S-transferases (GSTs) are pharmacological targets for several
      diseases, including cancer. Isoform specificity has been difficult to achieve due
      to their overlapping substrate selectivity. Here we demonstrate the utility of
      bivalent GST inhibitors and their optimization via combinatorial linker design. A
      combinatorial library with dipeptide linkers emanating symmetrically from a
      central scaffold (bis-3,5-aminomethyl benzoic acid, AMAB) to connect two
      ethacrynic acid moieties was prepared and decoded via iterative deconvolution,
      against the isoforms GSTA1-1 and GSTP1-1. The library yielded high affinity GSTA1
      1 selective inhibitors (70-120-fold selectivity) and with stoichiometry of one
      inhibitor: one GSTA1-1 dimer. Saturation Transfer Difference (STD) NMR with one
      of these inhibitors, with linker structure (Asp-Gly-AMAB-Gly-Asp) and K(D) = 42
      nM for GSTA1-1, demonstrates that the Asp-Gly linker interacts tightly with GSTA1
      1, but not P1-1. H/D exchange mass spectrometry was used to map the protein
      binding site and indicates that peptides within the intersubunit cleft and in the
      substrate binding site are protected by inhibitor from solvent exchange. A model
      is proposed for the binding orientation of the inhibitor, which is consistent
      with electrostatic complementarity between the protein cleft and inhibitor linker
      as the source of isoform selectivity and high affinity. The results demonstrate
      the utility of combinatorial, or "irrational", linker design for optimizing
      bivalent inhibitors.

PMID- 16802829
TI  - Chemistry of mangana- and rhenatricarbadecaboranyl tricarbonyl complexes:
      evidence for an associative mechanism of ligand substitution involving an eta6
      eta4 cage-slippage process analagous to eta5-eta3-cyclopentadienyl ring-slippage.
AB  - The reaction of the tricarbadecaboranyl anion, 6-Ph-nido-5,6,9-C(3)B(7)H(9)(-),
      with M(CO)(5)Br [M = Mn, Re] or [(eta(6)-C(10)H(8))Mn(CO)(3)(+)]BF(4)(-) yielded
      the half-sandwich metallatricarbadecaboranyl analogues of (eta(5)
      C(5)H(5))M(CO)(3) [M = Mn, Re]. For both 1,1,1-(CO)(3)-2-Ph-closo-1,2,3,4
      MC(3)B(7)H(9) [M = Mn (2) and Re (3)], the metal is eta(6)-coordinated to the
      puckered six-membered open face of the tricarbadecaboranyl cage. Reactions of 2
      and 3 with isocyanide at room temperature produced complexes 8-(CNBu(t))-8,8,8
      (CO)(3)-9-Ph-nido-8,7,9,10-MC(3)B(7)H(9) [M = Mn (4), Re (5)], having the cage
      eta(4)-coordinated to the metal. Photolysis of 4 and 5 then resulted in the loss
      of CO and the formation of 1-(CNBu(t))-1,1-(CO)(2)-2-Ph-closo-1,2,3,4
      MC(3)B(7)H(9) [M = Mn, Re (6)], where the cage is again eta(6)-coordinated to the
      metal. Reaction of 2 and 3 with 1 equiv of phosphine at room temperature produced
      the eta(6)-coordinated monosubstituted complexes 1,1-(CO)(2)-1-P(CH(3))(3)-2-Ph
      closo-1,2,3,4-MC(3)B(7)H(9) [M = Mn (7), Re (9)] and 1,1-(CO)(2)-1-P(C(6)H(5))(3)
      2-Ph-closo-1,2,3,4-MC(3)B(7)H(9) [M = Mn (8), Re (10)]. NMR studies of these
      reactions at -40 degrees C showed that substitution occurs by an associative
      mechanism involving the initial formation of intermediates having structures
      similar to those of the eta(4)-complexes 4 and 5. The observed eta(6)-eta(4) cage
      slippage is analogous to the eta(5)-eta(3) ring-slippage that has been proposed
      to take place in related substitution reactions of cyclopentadienyl-metal
      complexes. Reaction of 9 with an additional equivalent of P(CH(3))(3) gave 8,8
      (CO)(2)-8,8-(P(CH(3))(3))(2)-9-Ph-nido-8,7,9,10-ReC(3)B(7)H(9) (11), where the
      cage is eta(4)-coordinated to the metal. Photolysis of 11 resulted in the loss of
      CO and the formation of the disubstituted eta(6)-complex 1-CO-1,1
      (P(CH(3))(3))(2)-2-Ph-closo-1,2,3,4-ReC(3)B(7)H(9) (12).

PMID- 16802830
TI  - Nonchelated alkene and alkyne complexes of d(0) zirconocene pentafluorophenyl
      cations.
AB  - This paper describes the generation and properties of nonchelated d(0)
      zirconocene-aryl-alkene and alkyne adducts that are stabilized by the presence of
      beta-SiMe(3) substituents on the substrates and the weak nucleophilicity of the 
      C(6)F(5) ligand. The cationic complexes
      [(C(5)H(4)R)(2)Zr(C(6)F(5))][B(C(6)F(5))(4)] (4a: R = H, 4b: R = Me) were
      generated by methide abstraction from (C(5)H(4)R)(2)Zr(C(6)F(5))Me by Ph(3)C(+).
      NMR studies show that 4a,b contain an o-CF...Zr dative interaction and probably
      coordinate a PhCl molecule in PhCl solution. Addition of allyltrimethylsilane
      (ATMS) to 4a,b in C(6)D(5)Cl solution at low temperature produces an equilibrium
      mixture of (C(5)H(4)R)(2)Zr(C(6)F(5))(H(2)C=CHCH(2)SiMe(3))(+) (7a,b), 4a,b, and
      free ATMS. Similarly, addition of propargyltrimethylsilane (PTMS) to 4a produces
      an equilibrium mixture of Cp(2)Zr(C(6)F(5))(HCCCH(2)SiMe(3))(+) (8a), 4a, and
      free PTMS. The NMR data for 7a,b,and 8a are consistent with highly unsymmetrical
      substrate coordination and substantial polarization of the substrate multiple
      bond with significant positive charge buildup at C(int) and negative charge
      buildup at C(term). PTMS binds to 4a more strongly than ATMS does. The ATMS
      adducts undergo nondissociative alkene face exchange ("alkene flipping"), i.e.,
      exchange of the (C(5)H(4)R)(2)Zr(C(6)F(5))(+) unit between the two alkene
      enantiofaces without decomplexation of the alkene, on the NMR time scale.

PMID- 16802831
TI  - Magnetic spin effects in enzymatic reactions: radical oxidation of NADH by
      horseradish peroxidase.
AB  - A description of the elementary steps of the horseradish peroxidase (HRP)
      catalyzed oxidation of NADH is presented, along with a quantitative analysis of
      the magnetic-field dependence of the enzymatic reaction. In the absence of
      H(2)O(2), the catalytic cycle begins with single-electron transfer from NADH to
      native HRP to form the NADH(.+) radical cation and the ferroperoxidase
      intermediate (Per(2+)). The theoretical framework for the magnetic-field
      dependent recombination of radical pairs has been extended to describe the
      magnetic-field dependence of reaction rate constants for multi-spin paramagnetic
      pairs, including the NADH(.+) radical cation and Per(2+) that exist in a
      correlated quartet electronic spin state. Good agreement between the
      experimentally observed and the theoretically calculated magnetic-field
      dependences of the effective rate constants underlines the importance of the
      initial single-electron-transfer step and supports a model in which the catalytic
      cycle begins with the one-electron reduction of HRP by NADH.

PMID- 16802832
TI  - Counterion-controlled transition of a cationic gemini from submicroscopic to
      giant vesicles.
AB  - While much is known about the self-assembly of lipids on nanoscale, our
      understanding of their biologically relevant mesoscale organization remains
      incomplete. Here, we show for a cationic gemini lipid a sharp and reversible
      transition from small vesicles with an average diameter of approximately 40 nm to
      giant vesicles (GVs) with an average diameter of approximately 11 microm. This
      transition is dependent on proper [NaCl] and specific temperature. Below this
      transition and in the vicinity of the air/water interface, a series of mesoscale
      morphological transitions was observed, revealing complex structures resembling
      biological membranes. On the basis of microscopy experiments, a tentative [NaCl]
      versus temperature shape/size phase diagram was constructed. To explain this
      unprecedented transition, we propose a novel mechanism whereby a specific
      interaction of Cl(-) counterion with the cationic gemini surfactant initiates the
      formation of a commensurate solute counterion lattice with low spontaneous
      curvature. In keeping with the high bending rigidity of NaCl crystal, this
      tightly associated ionic lattice enslaves membrane curvature and the mesoscale 3
      D organization of this lipid.

PMID- 16802833
TI  - Single oligomer spectra probe chromophore nanoenvironments of tetrameric
      fluorescent proteins.
AB  - When analyzing the emission of a large number of individual chromophores embedded
      in a matrix, the spread of the observed parameters is a characteristic property
      for the particular chromophore-matrix system. To quantitatively assess the
      influence of the matrix on the single molecule emission parameters, it is
      imperative to have a system with a well-defined chromophore nanoenvironment and
      the possibility to alter these surroundings in a precisely controlled way. Such a
      system is available in the form of the visible fluorescent proteins, where the
      chromophore nanoenvironment is defined by the specific protein sequence. We
      analyze the influence of the chromophore embedding within this defined protein
      environment on the distribution of the emission maximum wavelength for a number
      of variants of the fluorescent protein DsRed, and show that this parameter is
      characteristic of the chromophore-protein matrix combination and largely
      independent of experimental conditions. We observe that the chemical changes in
      the vicinity of the chromophore of different variants do not account for the
      different distributions of emission maximum positions but that the flexibility of
      the chromophore surrounding has a dominant role in determining the distribution.
      We find, surprisingly, that the more rigid the chromophore surrounding, the
      broader the distribution of observed maximum positions. We hypothesize that,
      after a thermally induced reorientation in the chromophore surrounding, a more
      flexible system can easily return to its energetic minimum position by fast
      reorientation, while in more rigid systems the return to the energetic minimum
      occurs in a stepwise fashion, leading to the broader distribution observed.

PMID- 16802834
TI  - Nucleophilic additions of trimethylsilyl cyanide to cyclic oxocarbenium ions:
      evidence for the loss of stereoselectivity at the limits of diffusion control.
AB  - The limitations of stereoelectronic models in assessing the stereoselective
      nucleophilic substitution reactions of cyclic oxocarbenium ions at high reaction
      rates are discussed. Evidence is provided suggesting that the
      diastereoselectivity of nucleophilic substitution reactions is attenuated at the
      limits of diffusion control. The low diastereoselectivities observed in the
      reactions of trimethylsilyl cyanide with five- and six-membered ring oxocarbenium
      ions are attributed to the high reactivity of the nucleophile and its reactions
      with these electrophiles at diffusion control rates.

PMID- 16802835
TI  - Enantioselective total synthesis of avrainvillamide and the stephacidins.
AB  - In this article, full details regarding our total synthesis of avrainvillamide
      and the stephacidins are presented. After an introduction and summary of prior
      synthetic studies in this family of structurally complex anticancer natural
      products, the evolution of a final synthetic approach is described. Thus, a
      thorough description of three separate model studies is provided for construction
      of the characteristic bicyclo[2.2.2]diazaoctane ring system common to these
      alkaloids. The first and second approaches sought to build the core using formal
      Diels-Alder and vinyl radical pathways, respectively. Although these strategies
      failed in their primary objective, they fostered the development of a new and
      mechanistically intriguing method for the synthesis of indolic enamides such as
      those found in numerous bioactive natural products. The scope and generality of
      this simple method for the direct dehydrogenation of tryptophan derivatives is
      described. Finally, details of a third and successful route to the core of these
      alkaloids are described which features oxidative C-C bond formation.
      Specifically, the first heterocoupling of two different types of carbonyl species
      (ester and amide) is accomplished in good yield, on a preparative scale, and with
      complete stereocontrol. The information gained in these model studies enabled an
      enantioselective total synthesis of stephacidin A. The absolute configuration of
      these alkaloids was firmly established in collaboration with Professor William
      Fenical. A full account of our successful efforts to convert stephacidin A into
      stephacidin B via avrainvillamide is presented. Finally, the first analogues of
      these natural products have been prepared and evaluated for anticancer activity.

PMID- 16802836
TI  - Demonstrating oxygen loss and associated structural reorganization in the lithium
      battery cathode Li[Ni0.2Li0.2Mn0.6]O2.
AB  - The cathode in rechargeable lithium-ion batteries operates by conventional
      intercalation; Li+ is extracted from LiCoO2 on charging accompanied by oxidation
      of Co3+ to Co4+; the process is reversed on discharge. In contrast, Li+ may be
      extracted from Mn4+-based solids, e.g., Li2MnO3, without oxidation of Mn4+. A
      mechanism involving simultaneous Li and O removal is often proposed. Here, we
      demonstrate directly, by in situ differential electrochemical mass spectrometry
      (DEMS), that O2 is evolved from such Mn4+ -containing compounds,
      Li[Ni(0.2)Li(0.2)Mn(0.6)]O2, on charging and using powder neutron diffraction
      show that O loss from the surface is accompanied by diffusion of transition metal
      ions from surface to bulk where they occupy vacancies created by Li removal. The
      composition of the compound moves toward MO(2). Understanding such unconventional
      Li extraction is important because Li-Mn-Ni-O compounds, irrespective of whether
      they contain Co, can, after O loss, store 200 mAhg(-1) of charge compared with
      140 mAhg(-1) for LiCoO(2).

PMID- 16802838
TI  - NICE says no to inhaled insulin: what lessons should we learn?

PMID- 16802839
TI  - Economic models of antiretroviral therapy: searching for the optimal strategy.
AB  - The diffusion of protease inhibitors and non-nucleoside reverse transcriptase
      inhibitors in the US in 1996 and 1997 reduced the number of deaths attributable
      to HIV disease and changed the way we think about the illness. Today, HIV disease
      may be deemed a fairly expensive chronic condition rather than an intolerably
      expensive fatal illness. Although most studies have found that patients receiving
      new drug therapies are hospitalised less frequently than patients who received
      early drug therapies, it is unclear whether the diffusion of new drug therapies
      has increased or decreased the annual cost of care. However, it is evident that
      the diffusion of new drug therapies has increased the lifetime cost of care.
      Analysts rely on models to simulate the course and cost of HIV disease. This
      study reviews the evolution of these models, paying particular attention to how
      these models estimate the cost of care. The primary findings of this review are
      that the economic data used in these models are often too imprecise to accurately
      identify the cost of each disease stage and are almost always outdated. Moreover,
      it was found that estimates of drug costs in these models may not accurately
      reflect actual expenditures.

PMID- 16802840
TI  - Developing health-related quality-of-life instruments for use in Asia: the
      issues.
AB  - About half of the world's population live in Asia. Mandarin (the official
      language of China), Hindi and Japanese are among the ten languages spoken by the
      largest number of primary speakers. The numbers of Tamil and Malay speakers are
      expected to grow rapidly in the next few decades. Most health-related quality-of
      life (HR-QOL) instruments currently used in Asia are translations and/or
      adaptations of instruments developed in North America and Western Europe. We
      illustrate and discuss several major issues in the development of HR-QOL
      instruments for use in Asia. We have seen insufficient quality in translation and
      semantic equivalence, which is not a uniquely Asian problem. This problem will be
      alleviated by putting recently proposed guidelines for translation and adaptation
      of patient-reported outcomes into practice and formally conducting equivalence
      studies. For copyright or other reasons it is rare to see major adaptations, such
      as exclusion of a domain in the original instrument or inclusion of a new domain,
      made to existing instruments. Evidence is limited and mixed as to whether there
      are differences in the concepts of HR-QOL between Asian and North
      American/Western European cultures that are important enough to justify such
      major adaptations, or the development of indigenous instruments, as opposed to
      the translation/adaptation of existing instruments. There are substantial
      cultural differences concerning what questions are appropriate to ask and answer.
      Many HR-QOL instruments are designed for self-completion. This mode of
      administration is often not feasible in Asia because of low literacy rates and
      the presence of many different regional languages. Alternative administration
      methods and analytic strategies that allow for pooling data collected by
      different modes are needed. The availability of HR-QOL instruments in various
      Asian countries seems to reflect the status of economic development of the
      countries rather than their disease burden. For instance, many important HR-QOL
      instruments are available in Japanese but not in Hindi or Tamil.

PMID- 16802841
TI  - Cost of lung cancer: a methodological review.
AB  - Cost of illness (COI) studies estimate the overall economic burden of a specific
      disease, rather than simply treatment-related costs. While having been criticised
      for not allowing resource prioritisation, COI studies can provide useful
      guidance, so long as they adhere to accepted methodology. The aim of this review
      is to analyse the methods used to evaluate the cost of lung cancer. Because of
      the increasing incidence and high direct and indirect costs of lung cancer, it is
      an important disease in terms of economic implications, and therefore provides a
      relevant example with which to review COI study methodologies. First, the key
      points of the methodology relating to COI studies were identified. COI studies
      relating to lung cancer were then reviewed, focussing on an analysis of the
      different methods used and an identification of the strengths and weaknesses of
      each approach. The COI studies that were analysed confirmed that lung cancer is a
      costly illness, and that hospitalisation and treatments account for a large part
      of direct costs, while indirect costs represent a large part of the total costs.
      The review also showed that COI studies adopted significantly different
      approaches to estimate the costs of lung cancer, reflecting a lack of consensus
      on the methodology of COI studies in this area. Hence, to increase the
      credibility of COI studies, closer agreement among researchers on methodological
      principles would be desirable.

PMID- 16802843
TI  - Usefulness of the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL)
      questionnaire in patients with diabetes in a multi-ethnic Asian country.
AB  - INTRODUCTION: Asia will be at the forefront of the current epidemic of diabetes
      mellitus. Quality of life (QOL) is an important outcome measure in the assessment
      of diabetes care. However, few QOL instruments are culturally suitable for use in
      Asian countries. The Audit of Diabetes-Dependent Quality-of-Life (ADDQoL)
      questionnaire is a third-generation individualised QOL instrument. Individualised
      instruments such as the ADDQoL have the potential to be useful and less costly
      alternatives to computerised adaptive testing (CAT), which may not be practical
      in developing countries. OBJECTIVE: To evaluate and validate the ADDQoL
      questionnaire in English-speaking patients with diabetes in Singapore, a multi
      ethnic Asian country. METHODS: The ADDQoL and EQ-5D were administered to English
      speaking respondents with type 1 or 2 diabetes (aged > or =18 years) recruited
      from a tertiary acute-care referral hospital by convenience sampling. The
      usefulness of the key design features of the ADDQoL were assessed by measuring
      the number of zero-importance responses, the change in item ranking with and
      without weighting for importance, and the frequency of utilisation of the 'not
      applicable' (NA) options. The acceptability, factor structure and internal
      consistency (Cronbach's alpha) of the ADDQoL were also assessed. Data were
      subjected to unforced factor analysis with oblimin rotation and then the
      condition was set to force a one-factor solution. The validity of the ADDQoL was
      tested with the following hypotheses: those with moderate or severe problems on
      the EQ-5D would have worse ADDQoL average weighted impact (AWI) scores than those
      with a perfect health rating on the EQ-5D; those with better Present QOL scores
      on the ADDQoL would have better EQ-5D utility and visual analogue scale (VAS)
      scores; on the ADDQoL, AWI scores would correlate better with diabetes-dependent
      QOL than with Present QOL scores; and female respondents, those who required
      insulin or had longer duration of known diabetes would have worse ADDQoL AWI
      scores (known-group validity). RESULTS: We analysed data from 152 respondents
      (49% Chinese, 34% Indian; 45% female; mean age 52 years, range 18-80; mean
      duration of known diabetes 10 years, range 0-62). There were few missing data.
      Weighted scoring and NA options were shown to be necessary, thus supporting the
      usefulness of individualised health-related QOL measures. Factor structure of the
      ADDQoL was supported and internal consistency was high (alpha = 0.94). All
      hypotheses were fulfilled except for one that was partially fulfilled;
      respondents with longer duration of known diabetes did not report worse ADDQoL
      AWI scores. CONCLUSIONS: The ADDQoL is culturally appropriate, valid, reliable
      and well accepted among Singaporean patients with diabetes. Individualised
      measures such as the ADDQoL allow one to obtain precise score estimates and may
      offer developing countries a useful alternative to CAT.

PMID- 16802842
TI  - Hepatitis C: cost of illness and considerations for the economic evaluation of
      antiviral therapies.
AB  - Chronic hepatitis C virus (HCV) infection affects 170 million individuals
      worldwide. As it is detected incidentally through the evaluation of liver
      function tests or at the time of blood donor testing, it is usually clinically
      silent until the advanced stages of liver disease have occurred, when treatment
      is less effective and shortages of donor liver organs limit the therapeutic
      options. Combination therapy with ribavirin and pegylated interferon has resulted
      in sustained viral negative response rates of 54-61%. Because treatment is
      expensive and not uniformly effective, and because not all chronically infected
      patients will develop complications, concerns have arisen regarding the cost
      effectiveness of combination therapy. This paper reviews the public health and
      individual implications of HCV infections. Because of the latency of infection,
      numerous country-specific population analyses suggest that HCV will cause an
      increasing number of liver-related deaths over the next 10 years, despite the
      dramatic drop in incidence over the past 10-15 years. These deaths will be
      related to prevalent HCV infection from transfusion and injection drug use prior
      to identification of the virus and availability of screening tests in the late
      1980s and early 1990s. HCV can reduce life expectancy and impair quality of life,
      yet not all patients will develop progressive liver disease, and antiviral
      treatment may have associated adverse effects. Finally, to assess the value of
      antiviral drugs for HCV infection, this paper reviews studies examining the costs
      of antiviral drugs and of the disease itself along with response to antiviral
      therapy and the cost effectiveness of antiviral therapy. Although antiviral
      therapy appears to be expensive, when also considering the likelihood of
      sustained viral response to therapy, and the cost savings, quality-of-life
      improvement and prolongation of life expectancy from the prevention of HCV
      complications, antiviral treatment for HCV appears to be cost effective when
      compared with other well accepted medical interventions.

PMID- 16802844
TI  - Tapering off benzodiazepines in long-term users: an economic evaluation.
AB  - BACKGROUND: Discontinuation of benzodiazepine usage has never been evaluated in
      economic terms. This study aimed to compare the relative costs and outcomes of
      tapering off long-term benzodiazepine use combined with group cognitive
      behavioural therapy (TO+CBT), tapering off alone (TOA) and usual care. METHOD: A
      randomised controlled trial was conducted, incorporating a cost-effectiveness
      analysis from a societal as well as a pharmaceutical perspective. The cost of
      intervention treatment, prescribed drugs, healthcare services, productivity loss,
      and patients' costs were measured using drug prescription data and cost diaries.
      Costs were indexed at 2001 prices. The principal outcome was the proportion of
      patients able to discontinue benzodiazepine use during the 18-month follow-up. A
      secondary outcome measure was quality of life (Health Utility Index Mark III [HUI
      3] and the Medical Outcomes Study 36-item Short-Form Health Survey [SF-36]).
      RESULTS: A total of 180 patients were randomised to one of TO+CBT (n = 73), TOA
      (n = 73) or usual care (n = 34). Intervention treatment costs were an average of
      172.99Euro per patient for TO+CBT and 69.50Euro per patient for TOA. Both
      treatment conditions significantly reduced benzodiazepine costs during follow-up
      compared with usual care. The incremental cost-effectiveness ratios (ICERs)
      showed that, for each incremental 1% successful benzodiazepine discontinuation,
      TO+CBT cost 10.30-62.53Euro versus usual care, depending on the study
      perspective. However, TO+CBT was extendedly dominated or was dominated by TOA.
      This resulted in ICERs of 0.57Euro, 10.21Euro and 48.92Euro for TOA versus usual
      care from the limited pharmaceutical, comprehensive pharmaceutical and societal
      perspective, respectively. CONCLUSIONS: TO+CBT and TOA both led to a reduction in
      benzodiazepine costs. However, it remains uncertain which healthcare utilisation
      has a causal relationship with long-term benzodiazepine consumption or its
      treatment. Although the ICERs indicated better cost effectiveness for TOA than
      for TO+CBT, the differences were relatively small. The addition of group CBT to
      tapering off had no clinical or economic advantages. Extrapolation of our data
      showed that the investment in TOA was paid back after 19 months when corrected
      for treatment gain with usual care.

PMID- 16802845
TI  - Cost effectiveness of budesonide/formoterol for maintenance and reliever therapy
      versus salmeterol/fluticasone plus salbutamol in the treatment of asthma.
AB  - INTRODUCTION: Budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy
      (SMART) is an effective and well tolerated treatment option for patients with
      asthma. We compared the cost effectiveness from a societal perspective of this
      one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate
      (Seretide) plus salbutamol (albuterol) as needed (Seretide) Fixed Combination
      [SFC]). STUDY DESIGN: A cost-effectiveness analysis was performed based on
      effectiveness and resource-utilisation data collected prospectively in a
      randomised, 12-month study performed in 2143 patients in 16 countries. Resource
      utilisation data were pooled and unit costs (euro, year 2003 values) from Italy,
      France, the UK and Germany were used to generate estimates of direct and total
      costs per patient per year and cost per severe exacerbation avoided. METHODS:
      Adolescents and adults with asthma (n = 2143; mean forced expiratory volume in 1
      second [FEV(1)] 73% predicted; mean inhaled corticosteroid [ICS] dose 884
      microg/day) were randomised to SMART or SFC. The effectiveness measure used was
      the number of severe exacerbations per patient per year. Direct costs included
      medication use (budesonide/formoterol 160microg/4.5microg or
      salmeterol/fluticasone 50microg/100microg, 50microg/250microg or
      50microg/500microg plus salbutamol) and nonmedication-related resource use,
      including days in hospital, emergency room visits, specialist or primary care
      physician visits and other healthcare provider contacts. Indirect costs,
      including the number of days when the patient or their carer was unable to attend
      to their normal daily activities, were also assessed. The study assumed a
      European societal perspective (i.e. including direct and indirect costs).
      RESULTS: Treatment with SMART resulted in significantly fewer severe
      exacerbations per patient per year compared with SFC (0.24 vs 0.31 events per
      patient per year; p = 0.0025). Resource use was low in both groups. Medication
      costs accounted for the majority of the total costs. The increased effectiveness
      of SMART was achieved at a reduced or similar cost compared with SFC. SMART
      dominated when German unit costs were applied (i.e. there was a statistically
      significant reduction in both costs and number of exacerbations). In all other
      countries, the incremental cost-effectiveness ratios showed that there was a
      reduction in mean total cost per exacerbation avoided; however, this difference
      was not statistically significant. CONCLUSION: This analysis demonstrates that,
      compared with SFC, SMART may be cost effective from a societal perspective for
      the treatment of patients with asthma in Italy, Germany, France and the UK. SMART
      provided a reduction in the number of severe exacerbations per patient per year,
      at no statistically significant increase in cost - or even at a lower cost -
      compared with SFC plus as-needed reliever salbutamol.

PMID- 16802846
TI  - Clopidogrel: a pharmacoeconomic review of its use in patients with non-ST
      elevation acute coronary syndromes.
AB  - Clopidogrel (Plavix) is a selective inhibitor of adenosine diphosphate-induced
      platelet aggregation. In patients with acute coronary syndromes (ACS) [unstable
      angina or non-ST-segment elevation myocardial infarction], clopidogrel plus
      aspirin (acetylsalicylic acid) for up to 1 year significantly reduced the risk of
      cardiovascular events relative to placebo plus aspirin in the well designed
      clinical trial CURE (Clopidogrel in Unstable angina to prevent Recurrent Events)
      and its substudy in patients undergoing percutaneous coronary intervention (PCI)
      [PCI-CURE]. In pharmacoeconomic evaluations based on data from these trials
      conducted in a number of countries that used a variety of models, methods and/or
      type of costs, clopidogrel plus aspirin was consistently predicted to be cost
      effective relative to aspirin alone in the management of patients with ACS,
      including those undergoing PCI. Clopidogrel plus aspirin in patients with ACS
      reduced the incremental cost per cardiovascular event prevented and/or life-year
      gained (LYG) relative to aspirin alone in analyses using within-trial data
      (including longer-term analyses incorporating life-expectancy estimates) from the
      CURE or PCI-CURE studies. In Markov models of cost effectiveness with a lifetime
      horizon from a healthcare payer perspective based on the CURE trial, relative to
      aspirin alone, clopidogrel plus aspirin for 1 year was predicted to have
      incremental costs per LYG of 8132Euro in Spain (2003 values) and 1365Euro in
      Sweden (2000 values). In similar Swedish analyses from a healthcare payer
      perspective, clopidogrel plus aspirin for 1 year was predicted to have
      incremental costs per LYG of 10,993Euro (2004 values) relative to aspirin alone
      based on data from the PCI-CURE substudy. Broadly similar results have also been
      reported in modelled analyses from other countries. Cost-utility analyses based
      on the CURE trial suggest that, relative to lifelong aspirin alone, clopidogrel
      plus aspirin for 1 year followed by aspirin alone is associated with incremental
      costs per QALY gained that are below the traditional threshold of cost utility in
      Spain, the UK and the US. In patients with ACS, including those undergoing PCI,
      the addition of clopidogrel to standard therapy with aspirin is clinically
      effective in preventing cardiovascular events. Available pharmacoeconomic data
      from several countries, despite some inherent limitations, support the use of
      clopidogrel plus aspirin for up to 1 year as a cost-effective treatment relative
      to aspirin alone in this patient population.

PMID- 16802848
TI  - Pharmacokinetic/pharmacodynamic profile of voriconazole.
AB  - Voriconazole is the first available second-generation triazole with potent
      activity against a broad spectrum of clinically significant fungal pathogens,
      including Aspergillus,Candida, Cryptococcus neoformans, and some less common
      moulds. Voriconazole is rapidly absorbed within 2 hours after oral administration
      and the oral bioavailability is over 90%, thus allowing switching between oral
      and intravenous formulations when clinically appropriate. Voriconazole shows
      nonlinear pharmacokinetics due to its capacity-limited elimination, and its
      pharmacokinetics are therefore dependent upon the administered dose. With
      increasing dose, voriconazole shows a superproportional increase in area under
      the plasma concentration-time curve (AUC). In doses used in children (age < 12
      years) voriconazole pharmacokinetics appear to be linear. Steady-state plasma
      concentrations are reached approximately 5 days after both intravenous and oral
      administration; however, steady state is reached within 24 hours with
      voriconazole administered as an intravenous loading dose. The volume of
      distribution of voriconazole is 2-4.6 L/kg, suggesting extensive distribution
      into extracellular and intracellular compartments. Voriconazole was measured in
      tissue samples of brain, liver, kidney, heart, lung as well as cerebrospinal
      fluid. The plasma protein binding is about 60% and independent of dose or plasma
      concentrations. Clearance is hepatic via N-oxidation by the hepatic cytochrome
      P450 (CYP) isoenzymes, CYP2C19, CYP2C9 and CYP3A4. The elimination half-life of
      voriconazole is approximately 6 hours, and approximately 80% of the total dose is
      recovered in the urine, almost completely as metabolites. As with other azole
      drugs, the potential for drug interactions is considerable. Voriconazole shows
      time-dependent fungistatic activity against Candida species and time-dependent
      slow fungicidal activity against Aspergillus species. A short post-antifungal
      effect of voriconazole is evident only for Aspergillus species. The predictive
      pharmacokinetic/pharmacodynamic parameter for voriconazole treatment efficacy in
      Candida infections is the free drug AUC from 0 to 24 hour : minimum inhibitory
      concentration ratio.

PMID- 16802849
TI  - Tipranavir: a novel nonpeptidic protease inhibitor of HIV.
AB  - Tipranavir is a novel nonpeptidic protease inhibitor (PI) with activity against
      wild-type and multidrug-resistant HIV-1 both in vitro and in HIV-infected
      patients. Tipranavir/ritonavir 500 mg/200 mg administered twice daily for 3 weeks
      to healthy volunteers produced a median (range) maximum plasma concentration and
      minimum plasma concentration of 79.1 (34.9-111.7) mg/L and 19.5 (0.43-42.8) mg/L,
      respectively. Concomitant administration with low-dose ritonavir significantly
      increases tipranavir plasma concentrations; therefore, the recommended dose is
      tipranavir 500 mg and ritonavir 200 mg twice daily. Tipranavir is a substrate and
      inducer of cytochrome P450 3A4 isoenzyme, thus is predisposed to interactions
      with other agents that are substrates, inducers or inhibitors of this enzyme
      family. Significant drug-drug interactions have been reported with co
      administration of tipranavir/ritonavir and other PIs but not with the non
      nucleoside reverse transcriptase inhibitors, efavirenz and nevirapine.
      Tipranavir/ritonavir 500 mg/200 mg twice daily in combination with an optimised
      background regimen was more effective than a ritonavir-boosted comparator PI plus
      an optimised background regimen. The adverse effect profile for tipranavir is
      similar to other boosted PI regimens and most commonly includes gastrointestinal
      complaints. Severe adverse events that require close monitoring include
      hepatotoxicity and lipid abnormalities. Tipranavir retains activity in many
      highly treatment-experienced patients with a large number of protease mutations.
      Therefore, this novel PI in combination with ritonavir represents an important
      new choice in the treatment of multiple-PI-experienced patients.

PMID- 16802851
TI  - Morphine metabolite pharmacokinetics during venoarterial extra corporeal membrane
      oxygenation in neonates.
AB  - OBJECTIVE: To examine morphine metabolite serum concentrations in neonates
      undergoing venoarterial extra corporeal membrane oxygenation (ECMO) and to
      quantify clearance differences between these neonates and those subjected to
      noncardiac major surgery. PATIENTS AND METHODS: This was an observational study
      in level III referral centre. Fourteen neonates (< 7 days old) undergoing ECMO
      were included. Morphine and concomitant medications were given by protocol,
      adapted to the clinical conditions of the neonates. Pharmacokinetic findings were
      compared with those from a previous study in infants after noncardiac major
      surgery. Nonlinear mixed-effect modelling was used. Parameter estimates were
      standardised to a 70 kg person using allometric modeling RESULTS: Morphine-3
      glucuronide (M3G) was the predominant metabolite. Formation clearance to M3G at
      the start of ECMO on day 1 was lower than those in postoperative children, but
      matured more rapidly. After 10 days formation clearances of M3G in neonates on
      ECMO equalled those of postoperative children. Higher ECMO flows were associated
      with reduced formation clearances. Elimination clearances of M3G, but not
      morphine-6-glucuronide (M6G), were lower in the ECMO neonates; this was
      attributable to reduced renal clearance. These elimination clearances were
      correlated positively with ECMO flow and negatively with dopamine dose.
      Haemofiltration cleared M3G and M6G, but not morphine. CONCLUSION: Formation
      clearance to M3G, the predominant metabolite, is reduced during the first 10 days
      of ECMO. Elimination clearance of M3G and M6G is related to creatinine clearance.
      ECMO flow had a small effect on metabolite clearance. Higher flows were
      associated with decreased formation clearances, possibly reflecting illness
      severity. Dopamine dose reflected decreased renal clearance.

PMID- 16802852
TI  - Modelling the anti-migraine effects of BIBN 4096 BS: a new calcitonin gene
      related peptide receptor antagonist.
AB  - BACKGROUND AND OBJECTIVE: Migraine attacks are associated with release of the
      calcitonin gene-related peptide (CGRP) from trigeminal nerves. BIBN 4096 BS is
      the first CGRP receptor antagonist tested in humans showing response rates
      similar to those reported for triptans, together with very good safety and
      tolerability profiles. The objective of the current study is to develop a
      population pharmacokinetic/pharmacodynamic model resembling the mechanism of
      action of BIBN 4096 BS, and to extract by model-based simulations dosage
      formulations and pharmacodynamic properties that can assist in the development of
      CGRP receptor antagonists. METHODS: 126 patients with an acute moderate to severe
      migraine attack lasting not more than 6 hours were enrolled in this phase IIa
      study. BIBN 4096 BS was given as a single intravenous 10-minute infusion at
      different dose levels ranging from 0.25 to 10 mg. Severity of headache was
      measured up to 24 hours. Patients who did not show pain relief by 2 hours were
      allowed to take rescue medication. Severity of headache and time to rescue
      medication measurements were fitted simultaneously using logistic regression and
      time-to-event analysis with nonlinear mixed-effect modelling software NONMEM
      version V. RESULTS: Severity of headache and time to rescue medication were
      described as a function of the fraction of the CGRP receptors blocked by BIBN
      4096 BS, and controlled by the second- and first-order rate constants
      representing the onset (k(on)) and offset (k(off)) of the anti-migraine effects.
      The model predicted a slow rate of offset of the anti-migraine effect (half-life
      of k(off) = 21 hours). The model developed described the data well and was
      validated properly. DISCUSSION: A semi-mechanistic population
      pharmacokinetic/pharmacodynamic model has been developed for the anti-migraine
      effects of BIBN 4096 BS, characterised by the severity of headache and time to
      rescue medication. Simulations exploring the effect of the rate of absorption,
      bioavailability after an extravascular administration and the rate of
      activation/inactivation of the anti-migraine effect were performed. The rate of
      absorption seems to play a minor role; however, at least bioavailability
      fractions of 0.2-0.3 should be obtained. With regard to the kinetics of the anti
      migraine effect, and to achieve a response rate of 60% at 2 hours, values of
      k(on) should be > 0.081 mL/ng/h. At later times after administration higher
      values of k(off) are associated with faster offset of the response. The
      simulations showed that molecules with high k(on) and low k(off) values are the
      most promising.

PMID- 16802850
TI  - A mechanistic approach for the scaling of clearance in children.
AB  - BACKGROUND AND OBJECTIVE: Clearance is an important pharmacokinetic concept for
      scaling dosage, understanding the risks of drug-drug interactions and
      environmental risk assessment in children. Accurate clearance scaling to children
      requires prior knowledge of adult clearance mechanisms and the age-dependence of
      physiological and enzymatic development. The objective of this research was to
      develop and evaluate ontogeny models that would provide an assessment of the age
      dependence of clearance. METHODS: Using in vitro data and/or in vivo clearance
      values for children for eight compounds that are eliminated primarily by one
      process, models for the ontogeny of renal clearance, cytochrome P450 (CYP) 3A4,
      CYP2E1, CYP1A2, uridine diphosphate glucuronosyltransferase (UGT) 2B7, UGT1A6,
      sulfonation and biliary clearance were developed. Resulting ontogeny models were
      evaluated using six compounds that demonstrated elimination via multiple
      pathways. The proportion of total clearance attributed to each clearance pathway
      in adults was delineated. Each pathway was individually scaled to the desired
      age, inclusive of protein-binding prediction, and summed to generate a total
      plasma clearance for the child under investigation. The paediatric age range
      included in the study was premature neonates to sub-adults. RESULTS: There was
      excellent correlation between observed and predicted clearances for the model
      development (R2 = 0.979) and test sets (Q2 = 0.927). Clearance in premature
      neonates could also be well predicted (development R2 = 0.951; test Q2 = 0.899).
      CONCLUSION: Paediatric clinical trial development could greatly benefit from
      clearance scaling, particularly in guiding dosing regimens. Furthermore, since
      the proportion of clearance via different elimination pathways is age-dependent,
      information could be gained on the developmental extent of drug-drug
      interactions.

PMID- 16802853
TI  - Equivalent pharmacokinetics of the active metabolite of ciclesonide with and
      without use of the AeroChamber Plus spacer for inhalation.
AB  - BACKGROUND: Ciclesonide is an inhaled corticosteroid that provides safe and
      effective control of persistent asthma. Ciclesonide is administered as an aerosol
      solution in a metered-dose inhaler, using hydrofluoroalkane-134a as a propellant.
      It is activated in the lung to form its only active metabolite, desisobutyryl
      ciclesonide (des-CIC). A spacer may be used in combination with the
      hydrofluoroalkane metered-dose inhaler (HFA-MDI) to maintain inhaled
      corticosteroid delivery to the lung in patients with poor inhalation technique.
      OBJECTIVE: To determine if the pharmacokinetics of des-CIC and ciclesonide are
      altered when a spacer is used for ciclesonide inhalation. METHODS: A randomised,
      open-label, 2-period crossover, single-center pharmacokinetic study was conducted
      in 30 patients with asthma (forced expiratory volume in 1 second > or = 70%
      predicted). A single dose of ciclesonide (320 microg ex-actuator; equivalent to
      400 microg ex-valve) was administered via the HFA-MDI with and without an
      AeroChamber Plus spacer (Trudell Medical International, London, ON, Canada).
      Serum concentrations of ciclesonide and des-CIC were measured before inhalation
      and at various intervals until 14 hours after treatment using high-performance
      liquid chromatography with tandem mass spectrometric detection. RESULTS: The
      pharmacokinetic properties of the active metabolite, des-CIC, were equivalent
      after inhalation of ciclesonide with and without the AeroChamber Plus spacer.
      Point estimates and 90% confidence intervals (CIs) for the ratio of des-CIC
      pharmacokinetic properties in the presence or absence of a spacer were within the
      conventional bioequivalence range of 0.80-1.25 (area under the serum
      concentration time curve from time zero to infinity 0.96 [0.85, 1.07]; peak serum
      concentration 1.05 [0.94, 1.18]; elimination half-life 1.04 [0.92, 1.18]).
      Furthermore, there was no relevant difference in the point estimate and 90% CI of
      the difference of the time to reach peak serum concentration of des-CIC with or
      without a spacer. CONCLUSION: The AeroChamber Plus spacer did not influence the
      pharmacokinetics of the pharmacologically active des-CIC. Thus, systemic exposure
      to the active metabolite is similar when ciclesonide is inhaled with or without a
      spacer. Furthermore, these results are indicative of comparable lung deposition
      of ciclesonide in both the presence and absence of a spacer.

PMID- 16802854
TI  - Cerebrospinal fluid distribution of ketoprofen after intravenous administration
      in young children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the cerebrospinal fluid
      (CSF) distribution of an NSAID, ketoprofen, in children. Ketoprofen
      concentrations were determined from the CSF, plasma and protein-free plasma
      samples. METHODS: Children (n = 21), aged 13-94 months, were given intravenous
      ketoprofen (1 mg/kg) prior to surgery under spinal anaesthesia. Single venous
      blood and CSF samples from each patient were collected simultaneously 7-67
      minutes after the drug administration. Ketoprofen concentrations in the samples
      were determined using gas chromatography-mass spectrometry. RESULTS: Ketoprofen
      entered the CSF and was detectable in all samples. However, CSF delivery was
      limited; the ratio of ketoprofen concentration in CSF to plasma remained below
      0.006 at all times. Ketoprofen was highly bound (> 98%) to plasma proteins. The
      free ketoprofen fraction was not in equilibrium with the CSF, and no clear peak
      drug concentration in the CSF was observed. CONCLUSION: This study shows that
      ketoprofen is able to enter the CSF of children, which enables central analgesic
      effects of ketoprofen. However, the slow distribution of ketoprofen into the CSF
      and the apparently low absolute concentrations has to be taken into account when
      central analgesic effects are desired.

PMID- 16802855
TI  - Comparison of oxycodone pharmacokinetics after buccal and sublingual
      administration in children.
AB  - OBJECTIVE: We evaluated and compared the pharmacokinetics of two oral
      administration routes of oxycodone parenteral liquid (10 mg/mL)--single buccal
      and sublingual administration--in 30 generally healthy awake children, aged 6-91
      months. METHODS: Two groups of children undergoing inpatient surgery were
      enrolled. In a randomised fashion, children received a single dose of oxycodone
      0.2 mg/kg buccally (n = 15) or sublingually (n = 15). Regular blood samples were
      collected for up to 12 hours, and plasma was analysed for oxycodone, oxymorphone
      and noroxycodone using gas chromatography-mass spectrometry. RESULTS:
      Bioavailability was similar after administration at the two instillation sites.
      The area under the plasma concentration-time curve from time zero extrapolated to
      infinity (AUCinfinity) was 2400-8000 ng x min/mL (median 4200 ng x min/mL) in the
      buccal group and 2700-7900 ng x min/mL (median 5500 ng x min/mL) in the
      sublingual group. After buccal administration, maximum plasma concentration
      (Cmax) was 5.4-39 ng/mL (16 ng/mL) after buccal and 5.5-42 ng/mL (22 ng/mL) after
      sublingual administration. Twelve of the 15 children in both groups reached the
      oxycodone analgesic concentration of 12 ng/mL, which was sustained for 43-209
      minutes (median 160 minutes) in the children with buccal oxycodone and for 32-262
      minutes (median 175 minutes) in the children with sublingual oxycodone. The
      terminal elimination half-lives were closely similar in the two groups: 104-251
      minutes (median 140 minutes) in the buccal group and 110-190 minutes (150
      minutes) in the sublingual group. CONCLUSION: The results of this study show that
      in young children the absorption of oxycodone is similar after buccal and
      sublingual instillation.

PMID- 16802856
TI  - Is avoiding an aversive outcome rewarding? Neural substrates of avoidance
      learning in the human brain.
AB  - Avoidance learning poses a challenge for reinforcement-based theories of
      instrumental conditioning, because once an aversive outcome is successfully
      avoided an individual may no longer experience extrinsic reinforcement for their
      behavior. One possible account for this is to propose that avoiding an aversive
      outcome is in itself a reward, and thus avoidance behavior is positively
      reinforced on each trial when the aversive outcome is successfully avoided. In
      the present study we aimed to test this possibility by determining whether
      avoidance of an aversive outcome recruits the same neural circuitry as that
      elicited by a reward itself. We scanned 16 human participants with functional MRI
      while they performed an instrumental choice task, in which on each trial they
      chose from one of two actions in order to either win money or else avoid losing
      money. Neural activity in a region previously implicated in encoding stimulus
      reward value, the medial orbitofrontal cortex, was found to increase, not only
      following receipt of reward, but also following successful avoidance of an
      aversive outcome. This neural signal may itself act as an intrinsic reward,
      thereby serving to reinforce actions during instrumental avoidance.

PMID- 16802859
TI  - Primary processes during the light-signal transduction of phototropin.
AB  - Phototropin is a blue-light photoreceptor in plants that mediates phototropism,
      chloroplast relocation, stomata opening and leaf expansion. Phototropin molecule
      has two photoreceptive domains named LOV1 (light-oxygen-voltage) and LOV2 in the
      N-terminus and a serine/threonine kinase domain in the C-terminus, and acts as a
      blue light-regulated kinase. Each LOV domain binds a flavin mononucleotide as a
      chromophore and undergoes unique cyclic reactions upon blue-light absorption that
      comprises a cysteinyl-flavin adduct formation through a triplet-excited state and
      a successive adduct break to revert to the initial ground state. The molecular
      reactions underlying the photocycle are reviewed and one of the probable
      molecular schemes is presented. Adduct formation alters the secondary protein
      structure of the LOV domains. This structural change could be transferred to the
      linker between the kinase domain and involved in the photoregulation of the
      kinase activity. The structural changes as well as the oligomeric structures seem
      to differ between LOV1 and LOV2, which may explain the proposed roles of each
      domain in the photoregulation of the kinase activity. The photoregulation
      mechanism of phototropin kinase is reviewed and discussed in reference to the
      regulation mechanism of protein kinase A, which it resembles.

PMID- 16802857
TI  - Prevalence and evolution of core photosystem II genes in marine cyanobacterial
      viruses and their hosts.
AB  - Cyanophages (cyanobacterial viruses) are important agents of horizontal gene
      transfer among marine cyanobacteria, the numerically dominant photosynthetic
      organisms in the oceans. Some cyanophage genomes carry and express host-like
      photosynthesis genes, presumably to augment the host photosynthetic machinery
      during infection. To study the prevalence and evolutionary dynamics of this
      phenomenon, 33 cultured cyanophages of known family and host range and viral DNA
      from field samples were screened for the presence of two core photosystem
      reaction center genes, psbA and psbD. Combining this expanded dataset with
      published data for nine other cyanophages, we found that 88% of the phage genomes
      contain psbA, and 50% contain both psbA and psbD. The psbA gene was found in all
      myoviruses and Prochlorococcus podoviruses, but could not be amplified from
      Prochlorococcus siphoviruses or Synechococcus podoviruses. Nearly all of the
      phages that encoded both psbA and psbD had broad host ranges. We speculate that
      the presence or absence of psbA in a phage genome may be determined by the length
      of the latent period of infection. Whether it also carries psbD may reflect
      constraints on coupling of viral- and host-encoded PsbA-PsbD in the
      photosynthetic reaction center across divergent hosts. Phylogenetic clustering
      patterns of these genes from cultured phages suggest that whole genes have been
      transferred from host to phage in a discrete number of events over the course of
      evolution (four for psbA, and two for psbD), followed by horizontal and vertical
      transfer between cyanophages. Clustering patterns of psbA and psbD from
      Synechococcus cells were inconsistent with other molecular phylogenetic markers,
      suggesting genetic exchanges involving Synechococcus lineages. Signatures of
      intragenic recombination, detected within the cyanophage gene pool as well as
      between hosts and phages in both directions, support this hypothesis. The
      analysis of cyanophage psbA and psbD genes from field populations revealed
      significant sequence diversity, much of which is represented in our cultured
      isolates. Collectively, these findings show that photosynthesis genes are common
      in cyanophages and that significant genetic exchanges occur from host to phage,
      phage to host, and within the phage gene pool. This generates genetic diversity
      among the phage, which serves as a reservoir for their hosts, and in turn
      influences photosystem evolution.

PMID- 16802860
TI  - Functional insights gained from structural analyses of DNA duplexes that contain
      UV-damaged photoproducts.
AB  - Ultraviolet photolesions endow DNA with distinct structural and dynamic
      properties. Biophysical studies of photoproduct-containing DNA have shown that
      these lesions affect the mutagenic properties of DNA and damage recognition by
      DNA repair systems. Recently obtained high-resolution cocrystal structures of
      damaged DNA bound to either DNA polymerase or DNA repair enzymes have enriched
      our understanding of the mechanisms by which DNA lesions are bypassed or
      recognized by DNA metabolizing proteins. Here, we summarize the results of these
      structural studies and discuss their implications for DNA metabolism.

PMID- 16802858
TI  - Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration
      guidance.
AB  - Saccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads
      cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes
      emphasizes a conserved role in regulating sister chromatid cohesion, but homologs
      of Scc4 have not hitherto been identified outside certain fungi. Some metazoan
      orthologs of Scc2 were initially identified as developmental gene regulators,
      such as Drosophila Nipped-B, a regulator of cut and Ultrabithorax, and delangin,
      a protein mutant in Cornelia de Lange syndrome. We show that delangin and Nipped
      B bind previously unstudied human and fly orthologs of Caenorhabditis elegans MAU
      2, a non-axis-specific guidance factor for migrating cells and axons. PSI-BLAST
      shows that Scc4 is evolutionarily related to metazoan MAU-2 sequences, with the
      greatest homology evident in a short N-terminal domain, and protein-protein
      interaction studies map the site of interaction between delangin and human MAU-2
      to the N-terminal regions of both proteins. Short interfering RNA knockdown of
      human MAU-2 in HeLa cells resulted in precocious sister chromatid separation and
      in impaired loading of cohesin onto chromatin, indicating that it is functionally
      related to Scc4, and RNAi analyses show that MAU-2 regulates chromosome
      segregation in C. elegans embryos. Using antisense morpholino oligonucleotides to
      knock down Xenopus tropicalis delangin or MAU-2 in early embryos produced similar
      patterns of retarded growth and developmental defects. Our data show that sister
      chromatid cohesion in metazoans involves the formation of a complex similar to
      the Scc2-Scc4 interaction in the budding yeast. The very high degree of sequence
      conservation between Scc4 homologs in complex metazoans is consistent with
      increased selection pressure to conserve additional essential functions, such as
      regulation of cell and axon migration during development.

PMID- 16802861
TI  - Publishing negative results: the problem of publication bias.

PMID- 16802862
TI  - Gene expression does not change significantly in C3H 10T(1/2) cells after
      exposure to 847.74 CDMA or 835.62 FDMA radiofrequency radiation.
AB  - In vitro experiments with C3H 10T(1/2) mouse cells were performed to determine
      whether Frequency Division Multiple Access (FDMA) or Code Division Multiple
      Access (CDMA) modulated radiofrequency (RF) radiations induce changes in gene
      expression. After the cells were exposed to either modulation for 24 h at a
      specific absorption rate (SAR) of 5 W/ kg, RNA was extracted from both exposed
      and sham-exposed cells for gene expression analysis. As a positive control, cells
      were exposed to 0.68 Gy of X rays and gene expression was evaluated 4 h after
      exposure. Gene expression was evaluated using the Affymetrix U74Av2 GeneChip to
      detect changes in mRNA levels. Each exposure condition was repeated three times.
      The GeneChip data were analyzed using a two-tailed t test, and the expected
      number of false positives was estimated from t tests on 20 permutations of the
      six sham RF-field-exposed samples. For the X-ray-treated samples, there were more
      than 90 probe sets with expression changes greater than 1.3-fold beyond the
      number of expected false positives. Approximately one-third of these genes had
      previously been reported in the literature as being responsive to radiation. In
      contrast, for both CDMA and FDMA radiation, the number of probe sets with an
      expression change greater than 1.3-fold was less than or equal to the expected
      number of false positives. Thus the 24-h exposures to FDMA or CDMA RF radiation
      at 5 W/kg had no statistically significant effect on gene expression.

PMID- 16802863
TI  - Microarray gene expression profiling of a human glioblastoma cell line exposed in
      vitro to a 1.9 GHz pulse-modulated radiofrequency field.
AB  - The widespread use of mobile phones has led to public concerns about the health
      effects associated with exposure to radiofrequency (RF) fields. The paramount
      concern of most persons relates to the potential of these fields to cause cancer.
      Unlike ionizing radiation, RF fields used for mobile telecommunications (800-1900
      MHz) do not possess sufficient energy to directly damage DNA. Most rodent
      bioassay and in vitro genotoxicity/mutation studies have reported that RF fields
      at non-thermal levels have no direct mutagenic, genotoxic or carcinogenic
      effects. However, some evidence has suggested that RF fields may cause detectable
      postexposure changes in gene expression. Therefore, the purpose of this study was
      to assess the ability of exposure to a 1.9 GHz pulse-modulated RF field for 4 h
      at specific absorption rates (SARs) of 0.1, 1.0 and 10.0 W/kg to affect global
      gene expression in U87MG glioblastoma cells. We found no evidence that non
      thermal RF fields can affect gene expression in cultured U87MG cells relative to
      the nonirradiated control groups, whereas exposure to heat shock at 43 degrees C
      for 1 h up-regulated a number of typical stress-responsive genes in the positive
      control group. Future studies will assess the effect of RF fields on other cell
      lines and on gene expression in the mouse brain after in vivo exposure.

PMID- 16802864
TI  - Nuclear translocation and DNA-binding activity of NFKB (NF-kappaB) after exposure
      of human monocytes to pulsed ultra-wideband electromagnetic fields (1 kV/cm)
      fails to transactivate kappaB-dependent gene expression.
AB  - The objective of this study was to investigate whether exposure of human
      monocytes to a pulsed ultra-wideband electromagnetic field (EMF) of 1 kV/cm
      average peak power triggers a signaling pathway responsible for the
      transcriptional regulation of NFKB (NF-kappaB)-dependent gene expression. Human
      Mono Mac 6 (MM6) cells were exposed intermittently to EMF pulses for a total of
      90 min. The pulse width was 0.79+/-0.01 ns and the pulse repetition rate was 250
      pps. The temperature of the medium was maintained at 37 degrees C in both sham-
      and EMF-exposed flasks. Total NFKB DNA-binding activity was measured in the
      nuclear extracts by the electrophoretic mobility shift assay. Cells exposed to
      the EMFs and incubated for 24 h postexposure showed a 3.5+/-0.2-fold increase in
      the NFKB DNA-binding activity. Since activation of NFKB was observed, the
      possibility of kappaB-dependent gene expression in response to exposure to the
      EMFs was investigated using NFKB signal-specific gene arrays. The results
      revealed no difference in the NFKB-dependent gene expression profiles at 8 or 24
      h postexposure, indicating that activated NFKB does not lead to the differential
      expression of kappaB-dependent target genes. To determine whether the absence of
      the kappaB-dependent gene expression was due to compromised transcriptional
      regulation of NFKB, the functional activity of NFKB was examined in cells
      transiently transfected with Mercury Pathway constructs containing 4x NFKB
      binding sites associated either with the luciferase reporter system or a control
      vector. Pulsed EMF exposure did not induce NFKB-driven luciferase activity in
      these cells, indicating that the activation of NFKB at 24 h after the 1 kV/cm EMF
      exposure is functionally inactive. From these results, it is clear that the EMF
      induced NFKB activation is only a transient response, with minimal or no
      downstream effect.

PMID- 16802865
TI  - Exposure to radiofrequency radiation (900 MHz, GSM signal) does not affect
      micronucleus frequency and cell proliferation in human peripheral blood
      lymphocytes: an interlaboratory study.
AB  - The objective of this study was to investigate whether 24 h exposure to
      radiofrequency electromagnetic fields similar to those emitted by mobile phones
      induces genotoxic effects and/or effects on cell cycle kinetics in cultured human
      peripheral blood lymphocytes. The effect of 900 MHz exposure (GSM signal) was
      evaluated at four specific absorption rates (SARs, 0, 1, 5 and 10 W/kg peak
      values). The exposures were carried out in wire patch cells under strictly
      controlled conditions of both temperature and dosimetry, and the induction of
      genotoxic effects was evaluated in lymphocyte cultures from 10 healthy donors by
      applying the cytokinesis-block micronucleus assay. Positive controls were
      provided by using mitomycin C. Two research groups were involved in the study,
      one at ENEA, Rome, and the other at CNR-IREA, Naples. Each laboratory tested five
      donors, and the resulting slides were scored by both laboratories. Following this
      experimental scheme, it was also possible to compare the results obtained by
      cross-scoring of slides. The results obtained provided no evidence for the
      existence of genotoxic or cytotoxic effects in the range of SARs investigated.
      These findings were confirmed in the two groups of five donors examined in the
      two laboratories and when the same slides were scored by two operators.

PMID- 16802866
TI  - Effects of GSM-modulated radiofrequency electromagnetic fields on B-cell
      peripheral differentiation and antibody production.
AB  - We examined the effects of in vivo exposure to a GSM-modulated 900 MHz RF field
      on B-cell peripheral differentiation and antibody production in mice. Our results
      show that exposure to a whole-body average specific absorption rate (SAR) of 2
      W/kg, 2 h/day for 4 consecutive weeks does not affect the frequencies of
      differentiating transitional 1 (T1) and T2 B cells or those of mature follicular
      B and marginal zone B cells in the spleen. IgM and IgG serum levels are also not
      significantly different among exposed, sham-exposed and control mice. B cells
      from these mice, challenged in vitro with LPS, produce comparable amounts of IgM
      and IgG. Moreover, exposure of immunized mice to RF fields does not change the
      antigen-specific antibody serum level. Interestingly, not only the production of
      antigen-specific IgM but also that of IgG (which requires T-B-cell interaction)
      is not affected by RF-field exposure. This indicates that the exposure does not
      alter an ongoing in vivo antigen-specific immune response. In conclusion, our
      results do not indicate any effects of GSM-modulated RF radiation on the B-cell
      peripheral compartment and antibody production and thus provide no support for
      health-threatening effects.

PMID- 16802867
TI  - Increased radioresistance, g(2)/m checkpoint inhibition, and impaired migration
      of bone marrow stromal cell lines derived from Smad3(-/-) mice.
AB  - Smad3 protein is a prominent member of the Tgfb receptor signaling pathway.
      Smad3(-/-) mice display decreased radiation-induced skin fibrosis, suggesting a
      defect in both Tgfb-mediated fibroblast proliferation and migration. We
      established bone marrow stromal cell lines from Smad3(-/-) mice and homozygous
      littermate(+/+) mice. Smad3(-/-) cells displayed a significant increase in
      radiation resistance with a D(0)=2.25+/- 0.14 Gy compared to Smad3(+/+) cells
      with a D(0)=1.75+/- 0.03 (P=0.023). Radioresistance was abrogated by reinsertion
      of the human SMAD3 transgene, resulting in a D(0)=1.49 0.10 (P=0.028) for Smad3(
      /-)(3) cells. More Smad3(-/-) cells than Smad3(+/+) cells were in the G(2)/M
      phase; Smad3(-/-)(3) cells were similar to Smad3(+/+) cells. Smad3(+/+) cells
      exhibited increased apoptosis 24 h after 5 Gy (15%) or 8 Gy (43%) compared to
      less than 1% in Smad3(-/-) cells exposed to either dose. The movement of Smad3(-/
      ) cells, measured in an automated cell tracking system, was slower than that of
      Smad3(+/+) cells. Smad3(-/-)(3) cells resembled Smad3(+/+) cells. These studies
      establish concordance of a defective Tgfb signal transduction pathway, an
      increased proportion of G(2)/M cells, and radioresistance. The decreased
      migratory capacity of Smad3(-/-) cells in vitro correlates with decreased
      radiation fibrosis in vivo in mice deficient in Tgfb signaling.

PMID- 16802868
TI  - Decreased saliva secretion and down-regulation of AQP5 in submandibular gland in
      irradiated rats.
AB  - The molecular mechanisms of radiation-induced xerostomia remain unclear. The
      purpose of this study was to investigate the alterations of aquaporins (AQPs) and
      Na(+)/K(+)-ATPase in irradiated rat submandibular glands and to test the
      hypothesis that down-regulation of AQP5 expression in irradiated salivary glands
      is one of the mechanisms of radiation-induced xerostomia. Saliva from control and
      irradiated rat submandibular glands was analyzed. The mRNA level of AQP5 in the
      submandibular glands was assessed by semi-quantitative RT-PCR and in situ
      hybridization. The protein expression of AQP5, AQP1 and Na(+)/K(+)-ATPase was
      determined by Western blotting and immunohistochemistry. The body weight,
      submandibular gland weight, and saliva secretion of irradiated rats significantly
      decreased by 12, 24 and 32% on day 3 and 24, 16 and 38% on day 30
      postirradiation, respectively. There was a significant increase in the protein
      concentration and osmolality of saliva in irradiated rats on days 3 and 30
      postirradiation. However, there was no significant difference between irradiated
      and control rats in total saliva protein secretion. RT-PCR analysis showed that
      mRNA expression of AQP5 was significantly down-regulated by 37 and 51% in
      irradiated rats on days 3 and 30 postirradiation, respectively. Immunoblotting
      showed that the AQP5 protein level was decreased by 40 and 60% in irradiated
      glands, in contrast to the slight reductions of AQP1 and Na(+)/K(+)-ATPase
      proteins. Immunohistochemical analysis demonstrated that loss of AQP5 protein
      occurred throughout the irradiated glands, while no significant reduction was
      detected in AQP1 and Na(+)/ K(+)-ATPase labeling density. These results suggest
      that the preferential down-regulation of AQP5 with minor effects on AQP1 and
      Na(+)/K(+)-ATPase may contribute to radiation-induced salivary dysfunction.

PMID- 16802869
TI  - Inhibitory and stimulatory bystander effects are differentially induced by Iodine
      125 and Iodine-123.
AB  - The bystander effect, originating from cells irradiated in vitro, describes
      responses of surrounding cells not targeted by the radiation. Previously we
      demonstrated that the subcutaneous injection into nude mice of human
      adenocarcinoma LS174T cells lethally irradiated by Auger electrons from the decay
      of DNA-incorporated (125)I inhibits growth of co-injected LS174T cells
      (inhibitory bystander effect; Proc. Natl. Acad. Sci. USA 99, 13765-13770, 2002).
      We have repeated these studies using cells exposed to lethal doses of (123)I, an
      Auger electron emitter whose emission spectrum is identical to that of (125)I,
      and report herein that the decay of (123)I within tumor cell DNA stimulates the
      proliferation of neighboring unlabeled tumor cells growing subcutaneously in nude
      mice (stimulatory bystander effect). Similar inhibitory bystander effects
      ((125)I) and stimulatory bystander effects ((123)I) are obtained in vitro.
      Moreover, supernatants from cultures with (125)I-labeled cells are positive for
      tissue inhibitors of metalloproteinases (TIMP1 and TIMP2), and those from
      cultures with (123)I-labeled cells are positive for angiogenin. These findings
      call for the re-evaluation of current dosimetric approaches for the estimation of
      dose-response relationships in individuals after radiopharmaceutical
      administration or radiocontamination and demonstrate a need to adjust all
      "calculated" dose estimates by a dose modification factor (DMF), a radionuclide
      specific constant that factors in hitherto not-so-well recognized biophysical
      processes.

PMID- 16802870
TI  - Comparison of (125)I stereotactic brachytherapy and LINAC radiosurgery modalities
      based on physical dose distribution and radiobiological efficacy.
AB  - The goal of this study was to make a comparison between stereotactic
      brachytherapy implants and linear accelerator-based radiosurgery of brain tumors
      with respect to physical dose distributions and radiobiological efficacy. Twenty
      four treatment plans made for irradiation of brain tumors with low-dose-rate
      (125)I brachytherapy and multiple-arc LINAC-based radiosurgery were analyzed.
      Using the dose-volume histograms and the linear-quadratic model, the
      brachytherapy doses were compared to the brachytherapy-equivalent LINAC
      radiosurgery doses with respect to the predicted late effects of radiation on
      normal brain tissue. To characterize the conformity and homogeneity of dose
      distributions, the conformal index, external volume index, and relative
      homogeneity index were calculated for each dose plan and the mean values were
      compared. The average tumor volume was 5.6 cm(3) (range: 0.1-19.3 cm(3)). At low
      doses, the calculated radiobiological late effect on normal tissue was equivalent
      for external-beam and brachytherapy dose delivery. For brachytherapy at doses
      greater than 30 Gy, the calculated equivalent dose to normal tissues was less
      than for external-beam radiosurgery. However, the dose-calculated homogeneity was
      better for the LINAC radiosurgery, with a mean relative homogeneity index of 0.62
      compared to the calculated value of 0.19 for the brachytherapy (P=0.0002). These
      results are only predictions based on calculations concerning normal tissue
      tolerance. More data and research are needed to understand the clinical relevance
      of these findings.

PMID- 16802871
TI  - Contribution of indirect action to radiation-induced mammalian cell inactivation:
      dependence on photon energy and heavy-ion LET.
AB  - The contribution of indirect action mediated by OH radicals to cell inactivation
      by ionizing radiations was evaluated for photons over the energy range from 12.4
      keV to 1.25 MeV and for heavy ions over the linear energy transfer (LET) range
      from 20 keV/microm to 440 keV/microm by applying competition kinetics analysis
      using the OH radical scavenger DMSO. The maximum level of protection provided by
      DMSO (the protectable fraction) decreased with decreasing photon energy down to
      63% at 12.4 keV. For heavy ions, a protectable fraction of 65% was found for an
      LET of around 200 keV/microm; above that LET, the value stayed the same. The
      reaction rate of OH radicals with intracellular molecules responsible for cell
      inactivation was nearly constant for photon inactivation, while for the heavy
      ions, the rate increased with increasing LET, suggesting a reaction with the
      densely produced OH radicals by high-LET ions. Using the protectable fraction,
      the cell killing was separated into two components, one due to indirect action
      and the other due to direct action. The inactivation efficiency for indirect
      action was greater than that for direct action over the photon energy range and
      the ion LET range tested. A significant contribution of direct action was also
      found for the increased RBE in the low photon energy region.

PMID- 16802872
TI  - DNA fragmentation induced in human fibroblasts by accelerated (56)fe ions of
      differing energies.
AB  - DNA fragmentation was studied in the fragment size range 0.023-5.7 Mbp after
      irradiation of human fibroblasts with iron-ion beams of four different energies,
      i.e., 200 MeV/nucleon, 500 MeV/nucleon, 1 GeV/nucleon and 5 GeV/nucleon, with
      gamma rays used as the reference radiation. The double-strand break (DSB) yield
      (and thus the RBE for DNA DSB induction) of the four iron-ion beams, which have
      LETs ranging from 135 to 442 keV/mum, does not vary greatly as a function of LET.
      As a consequence, the variation of the cross section for DSB induction mainly
      reflects the variation in LET. However, when the fragmentation spectra were
      analyzed with a simple theoretical tool that we recently introduced, the results
      showed that spatially correlated DSBs, which are absent after gamma irradiation,
      increased markedly with LET for the iron-ion beams. This occurred because iron
      ions produce DNA fragments smaller than 0.75 Mbp with a higher probability than
      gamma rays (a probability that increases with LET). These sizes include those
      expected from fragmentation of the chromatin loops with Mbp dimensions. This
      result does not exclude a correlation at distances smaller than the lower size
      analyzed here, i.e. 23 kbp. Moreover, the DSB correlation is dependent on dose,
      decreasing when dose increases; this can be explained with the argument that at
      increasing dose there is an increasing fraction of fragments produced by DSBs
      caused by separate, uncorrelated tracks.

PMID- 16802873
TI  - Base release in nucleosides induced by low-energy electrons: a DFT study.
AB  - Low-energy electrons are known to induce strand breaks and base damage in DNA and
      RNA through fragmentation of molecular bonding. Recently the glycosidic bond
      cleavage of nucleosides by low-energy electrons has been reported. These
      experimental results call for a theoretical investigation of the strength of the
      C(1)'-N link in nucleosides (dA, dC and dT) between the base and deoxyribose
      before and after electron attachment. Through density functional theory (DFT)
      calculations, we compare the C(1)'-N bond strength, i.e., the bond dissociation
      energy of the neutral and its anionic radical, and find that an excess electron
      effectively weakens the C(1)'- N bond strength in nucleosides by 61-75 kcal/mol
      in the gas phase and 76-83 kcal/mol in the solvated environment. As a result,
      electron-induced fragmentation of the C(1)'-N bond in the gas phase is exergonic
      for dA (DeltaG=-14 kcal/mol) and for dT (DeltaG=-6 kcal/mol) and is endergonic
      (DeltaG=+1 kcal/ mol) only for dC. In the gas phase all the anionic nucleosides
      are found to be in valence states. Solvation is found to increase the exergonic
      nature by an additional 20 kcal, making the fragmentation both exothermic and
      exergonic for all nucleoside anion radicals. Thus C(1)'-N bond breaking in
      nucleoside anion radicals is found to be thermodynamically favorable both in the
      gas phase and under solvation. The activation barrier for the C(1)'-N bond
      breaking process was found to be about 20 kcal/mol in every case examined,
      suggesting that a 1 eV electron would induce spontaneous cleavage of the bond and
      that stabilized anion radicals on the DNA strand would undergo base release at
      only a modest rate at room temperature. These results suggest that base release
      from nucleosides and DNA is an expected consequence of low-energy electron
      induced damage but that the high barrier would inhibit this process in the stable
      anion radicals.

PMID- 16802874
TI  - Radiolytic transformation of 2,2',4'-trihydroxychalcone.
AB  - Radiolysis of 2,2',4'-trihydroxychalcone, a natural antioxidant present in fruit
      and vegetables, was performed in ethanol in the absence or in the presence of
      dioxygen. The degradation process of chalcone was followed in de-aerated solution
      by HPLC, NMR, FAB-LSIMS mass spectroscopy and analytical TLC. Under anaerobic
      conditions, six new products (three couples of diastereoisomers) were identified.
      Four of them kept the chalcone skeleton with OCH(2)CH(3), CH(OH)CH(3) and H
      substitutions on C(alpha) and C(beta). Thus the target was the alpha-beta double
      bond on which ethanol radicals were added. The two other compounds were formed in
      a second stage and exhibited a cyclization between the substituent on C(beta) and
      the carbonyl group. In the presence of dioxygen, these reactions were prevented
      and chalcone was protected. This study was the first step toward understanding of
      the behavior chalcone in irradiated fruits and vegetables.

PMID- 16802875
TI  - Can promotion of initiated cells be explained by excess replacement of radiation
      inactivated neighbor cells?
AB  - Recently, the observed promotion in the clonal expansion of a two-stage cancer
      model was attributed to a small excess replacement probability for the initiated
      cells. The proposed mechanism of excess replacement was evaluated for single
      intermediate cells surrounded by normal cells. This paper investigates this
      mechanism further using the same biological parameters. If the formation of
      clones of intermediate cells is taken into account in a quantitative analysis of
      the proposed mechanism, it turns out that (1) for the initial strong increase of
      the promotional effect with exposure, a much larger and unlikely excess
      replacement probability is needed, and (2) the leveling of the promotional effect
      for high exposures cannot be explained by multiple normal neighbors of an
      intermediate cell being inactivated within one cell cycle, as it had been
      suggested. Perhaps these discrepancies could be partly resolved by a re-scaling
      of the original parameters, but this should be investigated further.

PMID- 16802876
TI  - Some statistical issues in microarray gene expression data.
AB  - In this paper we discuss some of the statistical issues that should be considered
      when conducting experiments involving microarray gene expression data. We discuss
      statistical issues related to preprocessing the data as well as the analysis of
      the data. Analysis of the data is discussed in three contexts: class comparison,
      class prediction and class discovery. We also review the methods used in two
      studies that are using microarray gene expression to assess the effect of
      exposure to radiofrequency (RF) fields on gene expression. Our intent is to
      provide a guide for radiation researchers when conducting studies involving
      microarray gene expression data.

PMID- 16802878
TI  - The soft constraints hypothesis: a rational analysis approach to resource
      allocation for interactive behavior.
AB  - Soft constraints hypothesis (SCH) is a rational analysis approach that holds that
      the mixture of perceptual-motor and cognitive resources allocated for interactive
      behavior is adjusted based on temporal cost-benefit tradeoffs. Alternative
      approaches maintain that cognitive resources are in some sense protected or
      conserved in that greater amounts of perceptual-motor effort will be expended to
      conserve lesser amounts of cognitive effort. One alternative, the minimum memory
      hypothesis (MMH), holds that people favor strategies that minimize the use of
      memory. SCH is compared with MMH across 3 experiments and with predictions of an
      Ideal Performer Model that uses ACT-R's memory system in a reinforcement learning
      approach that maximizes expected utility by minimizing time. Model and data
      support the SCH view of resource allocation; at the under 1000-ms level of
      analysis, mixtures of cognitive and perceptual-motor resources are adjusted based
      on their cost-benefit tradeoffs for interactive behavior.

PMID- 16802877
TI  - Value from hedonic experience and engagement.
AB  - Recognizing that value involves experiencing pleasure or pain is critical to
      understanding the psychology of value. But hedonic experience is not enough. I
      propose that it is also necessary to recognize that strength of engagement can
      contribute to experienced value through its contribution to the experience of
      motivational force--an experience of the intensity of the force of attraction to
      or repulsion from the value target. The subjective pleasure/pain properties of a
      value target influence strength of engagement, but factors separate from the
      hedonic properties of the value target also influence engagement strength and
      thus contribute to the experience of attraction or repulsion. These additional
      sources of engagement strength include opposition to interfering forces,
      overcoming personal resistance, using the right or proper means of goal pursuit,
      and regulatory fit between the orientation and manner of goal pursuit.
      Implications of the contribution of engagement strength to value are discussed
      for judgment and decision making, persuasion, and emotional experiences.

PMID- 16802879
TI  - Neural dynamics of autistic behaviors: cognitive, emotional, and timing
      substrates.
AB  - What brain mechanisms underlie autism, and how do they give rise to autistic
      behavioral symptoms? This article describes a neural model, called the Imbalanced
      Spectrally Timed Adaptive Resonance Theory (iSTART) model, that proposes how
      cognitive, emotional, timing, and motor processes that involve brain regions such
      as the prefrontal and temporal cortex, amygdala, hippocampus, and cerebellum may
      interact to create and perpetuate autistic symptoms. These model processes were
      originally developed to explain data concerning how the brain controls normal
      behaviors. The iSTART model shows how autistic behavioral symptoms may arise from
      prescribed breakdowns in these brain processes, notably a combination of
      underaroused emotional depression in the amygdala and related affective brain
      regions, learning of hyperspecific recognition categories in the temporal and
      prefrontal cortices, and breakdowns of adaptively timed attentional and motor
      circuits in the hippocampal system and cerebellum. The model clarifies how
      malfunctions in a subset of these mechanisms can, through a systemwide vicious
      circle of environmentally mediated feedback, cause and maintain problems with
      them all.

PMID- 16802880
TI  - The place of white in a world of grays: a double-anchoring theory of lightness
      perception.
AB  - The specific gray shades in a visual scene can be derived from relative luminance
      values only when an anchoring rule is followed. The double-anchoring theory I
      propose in this article, as a development of the anchoring theory of Gilchrist et
      al. (1999), assumes that any given region (a) belongs to one or more frameworks,
      created by Gestalt grouping principles, and (b) is independently anchored, within
      each framework, to both the highest luminance and the surround luminance. The
      region's final lightness is a weighted average of the values computed, relative
      to both anchors, in all frameworks. The new model accounts not only for all
      lightness illusions that are qualitatively explained by the anchoring theory but
      also for a number of additional effects, and it does so quantitatively, with the
      support of mathematical simulations.

PMID- 16802882
TI  - Elemental representations of stimuli in associative learning.
AB  - This article reviews evidence and theories concerning the nature of stimulus
      representations in Pavlovian conditioning. It focuses on the elemental approach
      developed in stimulus sampling theory (R. C. Atkinson & W. K. Estes, 1963; R. R.
      Bush & F. Mosteller, 1951b) and extended by I. P. L. McLaren and N. J. Mackintosh
      (2000, 2002) and contrasts this with models that invoke notions of configural
      representations that uniquely code for different patterns of stimulus inputs
      (e.g., J. M. Pearce, 1987, 1994; R. A. Rescorla & A. R. Wagner, 1972; A. R.
      Wagner & S. E. Brandon, 2001). The article then presents a new elemental model
      that emphasizes interactions between stimulus elements. This model is shown to
      explain a range of behavioral findings, including those (e.g., negative
      patterning and biconditional discriminations) traditionally thought to be beyond
      the explanatory capabilities of elemental models. Moreover, the model offers a
      ready explanation for recent findings reported by R. A. Rescorla (2000, 2001,
      2002b) concerning the way that stimuli with different conditioning histories
      acquire associative strength when conditioned in compound.

PMID- 16802883
TI  - Talking nets: a multiagent connectionist approach to communication and trust
      between individuals.
AB  - A multiagent connectionist model is proposed that consists of a collection of
      individual recurrent networks that communicate with each other and, as such, is a
      network of networks. The individual recurrent networks simulate the process of
      information uptake, integration, and memorization within individual agents, and
      the communication of beliefs and opinions between agents is propagated along
      connections between the individual networks. A crucial aspect in belief updating
      based on information from other agents is the trust in the information provided.
      In the model, trust is determined by the consistency with the receiving agents'
      existing beliefs and results in changes of the connections between individual
      networks, called trust weights. These weights lead to a selective propagation and
      thus to the filtering out of less reliable information, and they implement H. P.
      Grice's (1975) maxims of quality and quantity in communication. The unique
      contribution of communicative mechanisms beyond intrapersonal processing of
      individual networks was explored in simulations of key phenomena involving
      persuasive communication and polarization, lexical acquisition, spreading of
      stereotypes and rumors, and a lack of sharing unique information in group
      decisions.

PMID- 16802881
TI  - Conceptualizing changes in behavior in intervention research: the range of
      possible changes model.
AB  - An international movement has focused on identifying evidence-based interventions
      that were developed to change psychological constructs and that are supported by
      controlled studies. However, inconsistent findings within individual intervention
      studies and among multiple studies raise critical problems in interpreting the
      evidence, and deciding when and whether an intervention is evidence-based. A
      theoretical and methodological framework (Range of Possible Changes [RPC] Model)
      is proposed to guide the study of change in intervention research. The authors
      recommend that future quantitative reviews of the research literature use the RPC
      Model to conceptualize, examine, and classify the available evidence for
      interventions. Future research should adopt the RPC Model to both develop theory
      driven hypotheses and conduct examinations of the instances in which
      interventions may or may not change psychological constructs.

PMID- 16802884
TI  - Modularity in cognition: framing the debate.
AB  - Modularity has been the subject of intense debate in the cognitive sciences for
      more than 2 decades. In some cases, misunderstandings have impeded conceptual
      progress. Here the authors identify arguments about modularity that either have
      been abandoned or were never held by proponents of modular views of the mind. The
      authors review arguments that purport to undermine modularity, with particular
      attention on cognitive architecture, development, genetics, and evolution. The
      authors propose that modularity, cleanly defined, provides a useful framework for
      directing research and resolving debates about individual cognitive systems and
      the nature of human evolved cognition. Modularity is a fundamental property of
      living things at every level of organization; it might prove indispensable for
      understanding the structure of the mind as well.

PMID- 16802885
TI  - Decision-making models of remember-know judgments: comment on Rotello, Macmillan,
      and Reeder (2004).
AB  - The sum-difference theory of remembering and knowing (STREAK) provides a
      sophisticated account of many interactions in the remember-know (R-K) area (C. M.
      Rotello, N. A. Macmillan, & J. A. Reeder, 2004). It assumes 2 orthogonal strength
      dimensions and oblique criterion planes. Another dual-process model (J. T. Wixted
      & V. Stretch, 2004) with one decision axis has also been applied to R-K judgments
      with considerable success and provides new insights into the processes involved.
      An analysis of the 4 major R-K interactions can also be explained by a simpler
      one-dimensional signal detection theory (J. C. Dunn, 2004a). However these models
      do not make contact with standard work on recognition memory, so their scope is
      limited. To bridge this gap, a global-matching model (a theory of distributed
      associative memory [TODAM]) for R-K judgments is proposed. This model can produce
      good fits to the data, and there are established experimental manipulations with
      which to test it. It provides further support for the idea that R judgments are
      based on associative information, whereas K judgments are based on item
      information.

PMID- 16802886
TI  - Deciding about decision models of remember and know judgments: a reply to Murdock
      (2006).
AB  - B. B. Murdock (2006) has interpreted remember-know data within a decision space
      defined by item and associative information, the fundamental variables in his
      general recognition memory model TODAM (B. B. Murdock, 1982). He has related
      parameters of this extended model to stimulus characteristics for several classic
      remember-know data sets. The authors show that this accomplishment is shared by
      both one- and two-dimensional signal-detection-based remember-know models (J. C.
      Dunn, 2004; C. M. Rotello, N. A. Macmillan, & J. A. Reeder, 2004; J. T. Wixted &
      V. Stretch, 2004), which can be represented in this same decision space and can
      be related to stimulus characteristics with similar success. Murdock claims that
      his model, unlike its competitors, is a process model; however, the process
      aspects of TODAM are not used in his application, and the decision aspects are
      identical to a previously proposed model. Murdock's claim that one competing
      model (STREAK; C. M. Rotello et al., 2004) is not fully specified is shown to be
      false. The new model is not superior to existing ones, but comparisons among the
      models to date are not definitive. The authors describe several strategies that
      might be applied to distinguish among them.

PMID- 16802887
TI  - Should Kohlberg's cognitive developmental approach to morality be replaced with a
      more pragmatic approach? Comment on Krebs and Denton (2005).
AB  - Krebs and Denton (2005) proposed that Kohlberg's cognitive developmental approach
      to morality be replaced by a pragmatic approach more relevant to everyday social
      behavior and the cooperative moral orders of society. Although the Krebs and
      Denton article raises some legitimate questions, their proposal is at best
      premature and provokes some serious concerns. Their starting point, that
      Kohlberg's model of morality is inadequate, is an evaluation shared by many neo
      Kohlbergians. Before the cognitive developmental approach is replaced, however,
      important contributions (e.g., Rest's schema interpretation of the stages) toward
      refining or improving the approach must be adequately considered. Evidence
      suggests that Krebs and Denton may have underestimated relations between moral
      judgment stages and social behavior, including sudden behavior in emergency
      situations.

PMID- 16802888
TI  - Explanatory limitations of cognitive-developmental approaches to morality.
AB  - In response to Gibbs' defense of neo-Kohlbergian models of morality, the authors
      question whether revisions in Kohlberg's model constitute a coherent refinement
      of the cognitive-developmental approach. The authors argue that neo-Kohlbergian
      measures of moral development assess an aspect of morality (the most
      sophisticated forms of moral reasoning available to people) that plays a
      relatively minor role in determining the moral judgments and behavioral decisions
      people make in their everyday lives. Attempts to conceptualize stages as schema
      and to redefine moral decision-making in terms of automaticity will not solve
      these problems. Flexibility is an important aspect of moral maturity. Observed
      relations between stages of moral development and various forms of social conduct
      do not establish that the structures of moral reasoning that define stages of
      moral development exert a significant causal impact on moral behavior. Although
      cognitive-developmental approaches are equipped to account for some aspects of
      morality, a more general framework that organizes the insights from other
      theoretical approaches is needed.

PMID- 16802889
TI  - Modeling drivers' visual attention allocation while interacting with in-vehicle
      technologies.
AB  - In 2 experiments, the authors examined how characteristics of a simulated traffic
      environment and in-vehicle tasks impact driver performance and visual scanning
      and the extent to which a computational model of visual attention (SEEV model)
      could predict scanning behavior. In Experiment 1, the authors manipulated task
      relevant information bandwidth and task priority. In Experiment 2, the authors
      examined task bandwidth and complexity, while introducing infrequent traffic
      hazards. Overall, task priority had a significant impact on scanning; however,
      the impact of increasing bandwidth was varied, depending on whether the relevant
      task was supported by focal (e.g., in-vehicle tasks; increased scanning) or
      ambient vision (e.g., lane keeping; no increase in scanning). The computational
      model accounted for approximately 95% of the variance in scanning across both
      experiments.

PMID- 16802891
TI  - Emotional intelligence, personality, and task-induced stress.
AB  - Emotional intelligence (EI) may predict stress responses and coping strategies in
      a variety of applied settings. This study compares EI and the personality factors
      of the Five Factor Model (FFM) as predictors of task-induced stress responses.
      Participants (N = 200) were randomly assigned to 1 of 4 task conditions, 3 of
      which were designed to be stressful. Results confirmed that low EI was related to
      worry states and avoidance coping, even with the FFM statistically controlled.
      However, EI was not specifically related to task-induced changes in stress state.
      Results also confirmed that Neuroticism related to distress, worry, and emotion
      focused coping, and Conscientiousness predicted use of task-focused coping. The
      applied utility of EI and personality measures is discussed.

PMID- 16802890
TI  - Play it again with feeling: computer feedback in musical communication of
      emotions.
AB  - Communication of emotions is of crucial importance in music performance. Yet
      research has suggested that this skill is neglected in music education. This
      article presents and evaluates a computer program that automatically analyzes
      music performances and provides feedback to musicians in order to enhance their
      communication of emotions. Thirty-six semi-professional jazz /rock guitar players
      were randomly assigned to one of 3 conditions: (1) feedback from the computer
      program, (2) feedback from music teachers, and (3) repetition without feedback.
      Performance measures revealed the greatest improvement in communication accuracy
      for the computer program, but usability measures indicated that certain aspects
      of the program could be improved. Implications for music education are discussed.

PMID- 16802892
TI  - Effects of implementation intentions on the self-reported frequency of drivers'
      compliance with speed limits.
AB  - This study tested the efficacy of implementation intentions in the context of
      drivers' speeding behavior. Participants (N = 300) completed self-report measures
      of goal intention and behavior, and they were randomly assigned to an
      experimental condition, which required them to specify an implementation
      intention, or a control condition. One month post-baseline, self-reported
      compliance with speed limits significantly increased for experimental
      participants but not for control participants. The effects of specifying an
      implementation intention on behavior increased with the strength of drivers' goal
      intentions. Finally, analysis of participants' implementation intentions revealed
      that specifying more behavioral strategies increased the frequency with which
      participants reported complying with the speed limit. Implications of the
      findings are discussed in relation to enhancing road safety interventions.

PMID- 16802893
TI  - Searching for signs, symbols, and icons: effects of time of day, visual
      complexity, and grouping.
AB  - Searching for icons, symbols, or signs is an integral part of tasks involving
      computer or radar displays, head-up displays in aircraft, or attending to road
      traffic signs. Icons therefore need to be designed to optimize search times,
      taking into account the factors likely to slow down visual search. Three factors
      likely to adversely affect visual search were examined: the time of day at which
      search was carried out, the visual complexity of the icons, and the extent to
      which information features in the icon were grouped together. The speed with
      which participants searched icon arrays for a target was slower early in the
      afternoon, when icons were visually complex and when information features in
      icons were not grouped together to form a single object. Theories of attention
      that account for both feature-based and object-based search best explain these
      findings and are used to form the basis for ways of improving icon design.

PMID- 16802894
TI  - What makes a girl (or a boy) popular (or unpopular)? African American children's
      perceptions and developmental differences.
AB  - Open-ended questions were used to obtain narrative accounts of what makes a girl
      (or a boy) popular (or unpopular) at school. The participants were 489 African
      American students in Grades 1, 4, and 7 recruited from high-risk inner-city
      neighborhoods. Appearance and self-presentation were mentioned the most in Grades
      4 and 7. Prosocial characteristics were especially relevant for popularity in
      Grade 1, as were studentship in Grade 4 and peer affiliations in Grade 7. Deviant
      behaviors were nominated for popularity more frequently in Grade 7 than in the
      younger grades and more for boys' popularity than for girls'. The mean deviance
      scores were negative in all grade levels, suggesting a normative peer culture.
      Male groups in Grade 7 showed significant homophily in reports of deviant
      behaviors.

PMID- 16802895
TI  - Emotional reminiscing and the development of an autobiographical self.
AB  - According to autobiographical memory theorists, past event conversations provide
      children with a framework for evaluating and connecting past events into a
      coherent autobiography (R. Fivush, 1994; K. Nelson, 1993; M. K. Welch-Ross,
      1995). Two studies were conducted to empirically examine the association between
      past event conversation style and an independent measure of children's self
      concept consistency. In Study 1, 50 New Zealand mothers discussed everyday past
      events with their children at 51 and 65 months of age. In Study 2, 51 New Zealand
      parents discussed 1 positive and 3 negative past events with their 5- and 6-year
      old children. The consistency of children's self-views was assessed in both
      studies using the Children's Self-View Questionnaire (R. Eder, 1990). Children's
      self-concept consistency was moderately associated with greater explanation of
      the causes and consequences of children's negative emotions, resolution through
      social contact, and evaluation of positive events but not with simple
      attributions of emotion. These findings implicate parent-child conversations as a
      medium through which children can begin to understand the personal meaning of
      past experiences.

PMID- 16802896
TI  - Responsive parenting: establishing early foundations for social, communication,
      and independent problem-solving skills.
AB  - Mothers whose infants varied in early biological characteristics (born at term, n
      = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target
      group (n = 133) or developmental feedback comparison group (n = 131) to determine
      whether learning responsive behaviors would facilitate infant development. The
      target condition included videotaped examples, problem-solving activities, and
      mothers' critique of their own behaviors through video procedures across 10 home
      visits. All target versus comparison mothers showed greater increases across
      multiple responsiveness behaviors observed in 4 assessments conducted across 6-13
      months of age; changes in emotionally supportive behaviors were strongest for
      target mothers of infants born at VLBW. Increased maternal responsiveness
      facilitated greater growth in target infants' social, emotional, communication,
      and cognitive competence, supporting a causal role for responsiveness on infant
      development. Although benefits were generally comparable across risk groups,
      aspects of social and emotional skills showed greater change for those born at
      VLBW. Evidence for responsiveness as a multidimensional construct was provided as
      well as the importance of different aspects of responsiveness mediating the
      effect of the intervention on different infant skill domains.

PMID- 16802897
TI  - Infants' early ability to segment the conversational speech signal predicts later
      language development: a retrospective analysis.
AB  - Two studies examined relationships between infants' early speech processing
      performance and later language and cognitive outcomes. Study 1 found that
      performance on speech segmentation tasks before 12 months of age related to
      expressive vocabulary at 24 months. However, performance on other tasks was not
      related to 2-year vocabulary. Study 2 assessed linguistic and cognitive skills at
      4-6 years of age for children who had participated in segmentation studies as
      infants. Children who had been able to segment words from fluent speech scored
      higher on language measures, but not general IQ, as preschoolers. Results suggest
      that speech segmentation ability is an important prerequisite for successful
      language development, and they offer potential for developing measures to detect
      language impairment at an earlier age.

PMID- 16802898
TI  - Reticent behavior and experiences in peer interactions in Chinese and Canadian
      children.
AB  - In this study, the authors examined relations between reticent behavior in
      unfamiliar peer situations and experiences in interactions in Chinese and
      Canadian children. Observational data were collected from samples of children at
      4 years of age in the People's Republic of China and Canada. The results
      indicated that relations between reticent behavior and peer initiations were
      similar in the 2 samples. The differences between the samples were mainly in peer
      responses. Reticent behavior was associated with peer rejection such as overt
      refusal and disagreement in the Canadian sample but with positive responses such
      as approval in the Chinese sample, particularly when children made low-power
      initiations. The results suggest that reticent children in China and Canada may
      have similar as well as different experiences in social interactions.

PMID- 16802899
TI  - Perception precedes computation: can familiarity preferences explain apparent
      calculation by human babies?
AB  - Two studies of 5-month-old infants explored whether a phenomenon reported by K.
      Wynn (1992) reflects a familiarity preference instead of a mathematical
      competence. Experiment 1 was a conceptual replication of Wynn's study. When data
      were analyzed with the relatively liberal statistical approach used by Wynn, the
      original phenomenon was replicated. However, an analysis of variance revealed
      that girls and boys behaved in different ways, and that boys did not behave as
      Wynn would have predicted. Experiment 2 was identical to Experiment 1, with one
      exception that should not have influenced computation: Infants in this study were
      completely familiarized with the test displays before testing. Again, the data
      revealed an interaction involving sex: Boys tended to be influenced by their
      familiarity with the test displays, whereas girls tended to behave as Wynn would
      have predicted. These findings are discussed with reference to the literature on
      sex differences--specifically the finding that male infants are typically
      immature relative to their female peers--as well as to articles that have been
      critical or supportive of Wynn's conclusions.

PMID- 16802900
TI  - The developmental and cultural contexts of objectified body consciousness: a
      longitudinal analysis of two cohorts of women.
AB  - Longitudinal analysis of 10-year follow-up data on objectified body
      consciousness, body esteem, weight-related attitudes and behaviors, and
      psychological well-being in 74 middle-aged and 72 young women tested hypotheses
      developed from age-related change and cohort differences models of body
      experience. Young women's body surveillance and body shame decreased, and their
      body esteem increased, supporting an age-related changes model. Relationships
      between variables were relatively consistent with the 2 cohorts across data
      waves, supporting a cohort differences model, although nonoverlapping cohorts
      limit the interpretation of the data. The importance of developmental context in
      understanding women's body experience is discussed.

PMID- 16802902
TI  - Is extracurricular participation associated with beneficial outcomes? Concurrent
      and longitudinal relations.
AB  - The authors examined the relations between participation in a range of high
      school extracurricular contexts and developmental outcomes in adolescence and
      young adulthood among an economically diverse sample of African American and
      European American youths. In general, when some prior self-selection factors were
      controlled, 11th graders' participation in school clubs and organized sports was
      associated with concurrent indicators of academic and psychological adjustment
      and with drug and alcohol use. In addition, participation in 11th grade school
      clubs and prosocial activities was associated with educational status and civic
      engagement at 1 year after high school. A few of the concurrent and longitudinal
      relations between activity participation and development were moderated by race
      and gender. Finally, breadth of participation, or number of activity contexts,
      was associated with positive academic, psychological, and behavioral outcomes.

PMID- 16802903
TI  - Life's little (and big) lessons: identity statuses and meaning-making in the
      turning point narratives of emerging adults.
AB  - A longitudinal study examined relations between 2 approaches to identity
      development: the identity status model and the narrative life story model.
      Turning point narratives were collected from emerging adults at age 23 years.
      Identity statuses were collected at several points across adolescence and
      emerging adulthood, as were measures of generativity and optimism. Narratives
      were coded for the sophistication of meaning-making reported, the event type in
      the narrative, and the emotional tone of the narrative. Meaning-making was
      defined as connecting the turning point to some aspect of or understanding of
      oneself. Results showed that less sophisticated meaning was associated
      particularly with the less advanced diffusion and foreclosure statuses, and that
      more sophisticated meaning was associated with an overall identity maturity
      index. Meaning was also positively associated with generativity and optimism at
      age 23, with stories focused on mortality experiences, and with a redemptive
      story sequence. Meaning was negatively associated with achievement stories.
      Results are discussed in terms of the similarities and differences in the 2
      approaches to identity development and the elaboration of meaning-making as an
      important component of narrative identity.

PMID- 16802901
TI  - Reactivity and regulation in children prenatally exposed to cocaine.
AB  - Children prenatally exposed to cocaine may be at elevated risk for adjustment
      problems in early development because of greater reactivity and reduced
      regulation during challenging tasks. Few studies have examined whether cocaine
      exposed children show such difficulties during the preschool years, a period
      marked by increased social and cognitive demands and by rapid changes in
      reactivity and regulation. The authors addressed this question by examining
      frustration reactivity and regulation of behavior during a problem-solving task
      in cocaine-exposed and -unexposed preschoolers. Participants were 174 4.5-year
      olds (M age = 4.55 years, SD = 0.09). Frustration reactivity was measured as
      latency to show frustration and number of disruptive behaviors, whereas
      regulation was measured as latency to approach and attempt the problem-solving
      task and number of problem-solving behaviors. Results indicated that cocaine
      exposed children took longer to attempt the problem-solving task but that cocaine
      exposed boys showed the most difficulties: They were quicker to express
      frustration and were more disruptive. Effect sizes were relatively small,
      suggesting both resilience and vulnerabilities.

PMID- 16802904
TI  - Precision of imitation as a function of preschoolers' understanding of the goal
      of the demonstration.
AB  - The authors argue that imitation is a flexible and adaptive learning mechanism in
      that children do not always reproduce all of the details they can from a
      demonstration. Instead, they vary their replications depending on their
      interpretation of the situation. Specifically, the authors propose that when
      children do not understand the overall reason for a model's behavior, they will
      be more likely to imitate precisely. By copying conservatively in these
      situations, children may have a good chance of reproducing the action of the
      model correctly. In contrast, when the reason for an action is clear, children
      will be more likely to deviate from the manners and flourishes of the model and
      use their own means to complete the action.

PMID- 16802905
TI  - The influence of another's perspective on children's recall of previously
      misconstrued events.
AB  - Children's abilities to reframe their memories of events after hearing another
      child's perspective of the same events were examined, and links between memory
      reframing, cognitive ability, and social competence were explored. Nine- to 11
      year-olds (N = 79) were told to imagine that the events in a narrated story
      happened to them. Next, they heard another story that described either the same
      events (experimental condition) or unrelated events (control condition) from
      another child's perspective. The children in the experimental group reframed
      their memories in light of the alternative perspective, whereas the children in
      the control condition did not. Children with higher cognitive scores had higher
      memory reframing scores and received higher social competence ratings than
      children with lower cognitive scores.

PMID- 16802906
TI  - S shape of a granular pile in a rotating drum.
AB  - The shape of a granular pile in a rotating drum is investigated. Using discrete
      elements method (DEM) simulations we show that the "S shape" obtained for high
      rotation speed can be accounted for by the friction on the end plates. A
      theoretical model which accounts for the effect of the end plates is presented
      and the equation of the shape of the free surface is derived. The model reveals a
      dimensionless number which quantifies the influence of the end plates on the
      shape of the pile. Finally, the scaling laws of the system are discussed and
      numerical results support our conclusions.

PMID- 16802907
TI  - Transverse instability of avalanches in granular flows down an incline.
AB  - Avalanche experiments on an erodible substrate are analyzed using the "partial
      fluidization" model of dense granular flows. The model identifies a family of
      propagating solitonlike avalanches with shape and velocity controlled by the
      inclination angle and the depth of the substrate. At high inclination angles, the
      solitons display a transverse instability, followed by coarsening and fingering
      similar to recent experimental observation. A primary cause for the transverse
      instability is directly related to the dependence of the soliton velocity on the
      granular mass trapped in the avalanche.

PMID- 16802908
TI  - Sensitivity of arrest in mode-coupling glasses to low-q structure.
AB  - We quantify, within mode coupling theory, how changes in the liquid structure
      affect that of the glass. Apart from the known sensitivity to the structure
      factor S(q) at wave vectors around the first sharp diffraction peak q0, we find a
      strong (and inverted) response to structure at wave vectors below this peak: an
      increase in S(q0/2) lowers the degree of arrest over a wide q-range. This strong
      sensitivity to "caged cage" packing effects, on length scales of order 2d, is
      much weaker in attractive glasses where short-range bonding dominates the steric
      caging effect.

PMID- 16802909
TI  - Dielectric dispersion for short double-strand DNA.
AB  - A complex dielectric constant for double-strand DNA molecules with a length of
      not greater than 120 base pairs in an aqueous solution containing 30 mM NaCl was
      systematically measured as a function of chain length in such a way that
      experimental uncertainties associated with the molecular-weight distribution of
      specimens were virtually excluded. In contrast to the past experimental and
      theoretical studies for much longer DNA molecules, both the molar specific
      dielectric increment and the relaxation time are proportional to the chain
      length. These scaling rules cannot be accounted for by any theory so far proposed
      that gives analytical expressions for those two quantities in the long-chain
      limit.

PMID- 16802910
TI  - Force-induced deformations and stability of biological bonds.
AB  - A deformation model of the forced-induced dissociation of biological bonds is
      developed. A simple illustration shows that protein deformations can change the
      receptor-ligand interaction linearly with applied force at small forces, either
      increasing or decreasing the bond stability, and that a minor external work can
      lead to notable changes in the interaction energy. The deformation-induced
      increase of bond stability is illustrated with the remarkable catch-bond
      phenomenon in P and L selections. Additionally, the model rationalizes the
      frequently seen disparity between the bond dissociation rates of many free
      complexes and the zero-force asymptotic rates measured by force spectroscopy.

PMID- 16802911
TI  - Effects of the eye phase in DNA unzipping.
AB  - The onset of the "eye phase" (a phase consisting of configurations of eye-type
      conformations or bubbles in the double-stranded DNA) and its role during the DNA
      unzipping is studied when a force is applied to the interior of the chain. The
      directionality of the hydrogen bond introduced here shows oscillations in force
      extension curve similar to a "sawtooth" kind of oscillations seen in the protein
      unfolding experiments. The effects of intermediates (hairpins) and stacking
      energies on the melting profile have also been discussed.

PMID- 16802912
TI  - Escape rate from a metastable state weakly interacting with a heat bath driven by
      external noise.
AB  - Based on a system-reservoir model, where the reservoir is driven by an external
      stationary, Gaussian noise with arbitrary decaying correlation function, we study
      the escape rate from a metastable state in the energy diffusion regime. For the
      open system we derive the Fokker-Planck equation in the energy space and
      subsequently calculate the generalized non-Markovian escape rate from a
      metastable well in the energy diffusion domain. By considering the dynamics in a
      model cubic potential we show that the results obtained from numerical simulation
      are in good agreement with the theoretical prediction. It has been also shown
      numerically that the well-known turnover feature can be restored from our model.

PMID- 16802913
TI  - Statistical properties of functionals of the paths of a particle diffusing in a
      one-dimensional random potential.
AB  - We present a formalism for obtaining the statistical properties of functionals
      and inverse functionals of the paths of a particle diffusing in a one-dimensional
      quenched random potential. We demonstrate the implementation of the formalism in
      two specific examples: (1) where the functional corresponds to the local time
      spent by the particle around the origin and (2) where the functional corresponds
      to the occupation time spent by the particle on the positive side of the origin,
      within an observation time window of size t. We compute the disorder average
      distributions of the local time, the inverse local time, the occupation time, and
      the inverse occupation time and show that in many cases disorder modifies the
      behavior drastically.

PMID- 16802914
TI  - Multiscaling of correlation functions in single species reaction-diffusion
      systems.
AB  - We derive the multi-scaling of probability distributions of multi-particle
      configurations for the binary reaction-diffusion system in A + A --> O in d < or
      =2 and for the ternary system in 3A --> O in d=1. For the binary reaction we find
      that the probability Pt(N, Delta V) of finding N particles in a fixed volume
      element Delta V at time t decays in the limit of large time as (ln t/t)N(ln t)
      N(N-1)/2 for d=2 and t-Nd/2 t-N(N-1)epsilon/4+O(epsilon2) for d<2. Here epsilon=2
      d. For the ternary reaction in one dimension we find that Pt(N, delta V)
      approximately (ln t/t)N/2(ln t)-N(N-1)(N-2)/6 . The principal tool of our study
      is the dynamical renormalization group. We compare predictions of epsilon
      expansions for Pt(N, Delta V) for a binary reaction in one dimension against the
      exact known results. We conclude that the epsilon corrections of order two and
      higher are absent in the previous answer for Pt(N, Delta V) for N=1, 2, 3, 4.
      Furthermore, we conjecture the absence of epsilon2 corrections for all values of
      N.

PMID- 16802915
TI  - Analytic solution of neural network with disordered lateral inhibition.
AB  - The replica method has played a key role in analyzing systems with disorder,
      e.g., the Sherrington-Kirkpatrick (SK) model, and associative neural networks.
      Here we study the influence of disorder in the lateral inhibition type
      interactions on the cooperative and uncooperative behavior of recurrent neural
      networks by using the replica method. Although the interaction between neurons
      has a dependency on distance, our model can be solved analytically. Bifurcation
      analysis identifies the boundaries between paramagnetic, ferromagnetic, spin
      glass, and localized phases. In the localized phase, the network shows a bump
      like activity, which is often used as a model of spatial working memory or
      columnar activity in the visual cortex. Simulation results show that disordered
      interactions can stabilize the drift the of bump position, which is commonly
      observed in conventional lateral inhibition type neural networks.

PMID- 16802916
TI  - Long-time behavior of spreading solutions of Schrodinger and diffusion equations.
AB  - We investigate the asymptotic time behavior of the solutions of a large class of
      linear differential equations that generalize the free-particle Schrodinger and
      diffusion equations, containing the standard ones as particular cases. We find
      general scalings that depend only on characteristic features of both the
      arbitrary initial condition and the Green function associated with the evolution
      equation. Basically, the amplitude of a long-time solution can be expressed in
      terms of low order moments of the initial condition (if finite) and low order
      spatial derivatives of the Green function. These derivatives can also be of the
      fractional type, which naturally arise when moments are divergent. We apply our
      results to a large class of differential equations that includes the fractional
      Schrodinger and Levy diffusion equations. In particular, we show that, except for
      threshold cases, the amplitude of a packet may follow the asymptotic law t-alpha,
      with arbitrary positive alpha.

PMID- 16802917
TI  - Mechanical coupling in flashing ratchets.
AB  - We consider the transport of rigid objects with internal structure in a flashing
      ratchet potential by investigating the overdamped behavior of a rodlike chain of
      evenly spaced point particles. In one dimension, analytical arguments show that
      the velocity can reverse direction multiple times in response to changing the
      size of the chain or the temperature of the heat bath. The physical reason is
      that the effective potential experienced by the mechanically coupled objects can
      have a different symmetry than that of individual objects. All analytical
      predictions are confirmed by Brownian dynamics simulations. These results may
      provide a route to simple, coarse-grained models of molecular motor transport
      that incorporate an object's size and rotational degrees of freedom into the
      mechanism of transport.

PMID- 16802918
TI  - Brownian motor with time-delayed feedback.
AB  - An inertial Brownian motor with time-delayed feedback driven by an unbiased time
      periodic force is investigated. It is found that the mean velocity and the
      rectification efficiency are decreased when the noise intensity is increased.
      While the shape of the mean velocity and the rectification efficiency can be
      changed from one peak to two peaks when the time delay is increased, the symmetry
      in the velocity probability distribution function is broken when the delay time
      is increased.

PMID- 16802919
TI  - Diffusion enhancement in a periodic potential under high-frequency space
      dependent forcing.
AB  - We study the long-time behavior of an underdamped Brownian particle moving
      through a viscous medium and in a systematic potential, when it is subjected to a
      space-dependent high-frequency periodic force. When the frequency is very large,
      much larger than all other relevant system-frequencies, there is a Kapitsa time
      window wherein the effect of frequency-dependent forcing can be replaced by a
      static effective potential. Our analysis includes the case in which the forcing,
      in addition to being frequency-dependent, is space-dependent as well. The results
      of our analysis then lead to additional contributions to the effective potential.
      These are applied to the numerical calculation of the diffusion coefficient (D)
      for a Brownian particle moving in a periodic potential. Presented are numerical
      results, which are in excellent agreement with theoretical predictions and which
      indicate a significant enhancement of D due to the space-dependent forcing terms.
      In addition, we study the transport property (current) of an underdamped Brownian
      particle in a ratchet potential.

PMID- 16802920
TI  - Reaction-diffusion front width anomalies in disordered media.
AB  - We study the front characteristics of the A + B --> C reaction-diffusion system
      with initially separated reactants in disordered media, exemplified by two
      dimensional (2D) percolation. We investigate the front characteristics as a
      function of the disorder degree in this system, in particular close to
      criticality. We show that the front width exponent is larger than the mean-field
      (MF) exponent of 1/6, and at criticality it approaches 1/4, which is the one
      dimensional (1D) exponent. We show that previous predictions in the literature
      for the 2D percolation cluster at criticality are wrong. The results are
      discussed in the context of other systems with attenuated transport where the
      front width exponent is smaller than the MF exponent. We also study the short
      time behavior of the front width exponent, and discuss the validity of the
      scaling relations between the relevant exponents.

PMID- 16802921
TI  - Quantitative approach to small-scale nonequilibrium systems.
AB  - In a nanoscale system out of thermodynamic equilibrium, it is important to
      account for thermal fluctuations. Typically, the thermal noise contributes
      fluctuations, e.g., of distances that are substantial in comparison to the size
      of the system and typical distances measured. If the thermal fluctuations are
      ignored, misinterpretation of measured quantities such as interaction forces,
      potentials, and constants may result. Here, we consider a particle moving in a
      time-dependent landscape, as, e.g., in an optical tweezers or atomic force
      nanoscopic measurement. Based on the Kramers equation [H. A. Kramers, Physica 7,
      284 (1940)], we propose an approximate but quantitative way of dealing with such
      an out-of-equilibrium system. The limits of this approximate description of the
      escape process are determined through optical tweezers experiments and comparison
      to simulations. Also, this serves as a recipe for how to use the proposed method
      to obtain knowledge about the underlying energy landscape from a set of
      experimental measurements. Finally, we perform estimates of the error made if
      thermal fluctuations are ignored.

PMID- 16802922
TI  - Oscillation of viscous drops with smoothed particle hydrodynamics.
AB  - We investigate the nonlinear oscillations of heat-conductive, viscous, liquid
      drops in vacuum with zero gravity, using smoothed particle hydrodynamics (SPH).
      The liquid drops are modeled as a van der Waals fluid in two dimensions so that
      the models apply to flat, disklike drops. Attention is focused on small- to large
      amplitude oscillations of drops that are released from a static elliptic shape.
      We find that for small-amplitude motions the combined dissipative effects of
      finite viscosity and heat conduction induce rapid decay of the oscillations after
      a few periods, while for large-amplitude motions wave damping is governed by the
      action of both viscous dissipation and surface tension forces. The transition
      from periodic to aperiodic decay at Re approximately 1 as well as the quadratic
      decrease of the frequency with the initial aspect ratio at large Re are
      reproduced in good agreement with previous theoretical predictions and
      experimental results.

PMID- 16802923
TI  - Electrical impedance for an electrolytic cell.
AB  - We analyze in which experimental conditions the concept of electrical impedance
      is useful for an electrolytic cell. The analysis is performed by solving
      numerically the differential equations governing the phenomenon of the
      redistribution of the ions in the presence of an external electric field and
      comparing the results with the ones obtained by solving the linear approximation
      of these equations. The control parameter in our study is the amplitude of the
      applied voltage, assumed a simple harmonic function of the time. We show that the
      bulk distribution of ions close to the electrodes differs from the one obtained
      by means of the linear analysis already for small amplitudes of the applied
      voltage. Nevertheless, the concept of electrical impedance remains valid. For
      larger amplitudes, the current in the circuit is no longer harmonic at the same
      frequency of the applied voltage. Therefore the concept of electrical impedance
      is no longer meaningful.

PMID- 16802924
TI  - Molecular dynamics simulation of electro-osmotic flows in rough wall
      nanochannels.
AB  - We performed equilibrium and nonequilibrium molecular dynamics simulation to
      study electro-osmotic flows inside charged nanochannels with different types of
      surface roughness. We modeled surface roughness as a sequence of two-dimensional
      subnanoscale grooves and ridges (step function-type roughness) along the flow
      direction. The amplitude, spatial period, and symmetry of surface roughness were
      varied. The amplitude of surface roughness was on the order of the Debye length.
      The walls have uniform negative charges at the interface with fluids. We included
      only positive ions (counterions) for simplicity of computation. For the smooth
      wall, we compared our molecular dynamics simulation results to the well-known
      Poisson-Boltzmann theory. The density profiles of water molecules showed
      "layering" near the wall. For the rough walls, the density profiles measured from
      the wall are similar to those for the smooth wall except near where the steps are
      located. Because of the layering of water molecules and the finite size effect of
      ions and the walls, the ionic distribution departs from the Boltzmann
      distribution. To further understand the structure of water molecules and ions, we
      computed the polarization density. Near the wall, its z component dominates the
      other components, indicating the preferred orientation ("ordering") of water
      molecules. Especially, inside the groove for the rough walls, its maximum is 10%
      higher (stronger ordering) than for the smooth wall. The dielectric constant,
      computed with a Clausius-Mosotti-type equation, confirmed the ordering near the
      wall and the enhanced ordering inside the groove. The residence time and the
      diffusion coefficient, computed using the velocity autocorrelation function,
      showed that the diffusion of water and ions along the direction normal to the
      wall is significantly reduced near the wall and further decreases inside the
      groove. Along the flow direction, the diffusion of water and ions inside the
      groove is significantly lowered while it is similar to the bulk value elsewhere.
      We performed nonequilibrium molecular dynamics simulation to compute electro
      osmotic velocities and flow rates. The velocity profiles correspond to those for
      overlapped electric double layers. For the rough walls, velocity inside the
      groove is close to zero, meaning that the channel height is effectively reduced.
      The flow rate was found to decrease as the period of surface roughness decreases
      or the amplitude of surface roughness increases. We defined the zeta potential as
      the electrostatic potential at the location of a slip plane. We computed the
      electrostatic potential with the ionic distribution and the dielectric constant
      both from our molecular dynamics simulation. We estimated the slip plane from the
      velocity profile. The zeta potential showed the same trend as the flow rate: it
      decreases with an increasing amplitude and a decreasing period of surface
      roughness.

PMID- 16802925
TI  - Family of tunable spherically symmetric potentials that span the range from hard
      spheres to waterlike behavior.
AB  - We investigate the equation of state, diffusion coefficient, and structural order
      of a family of spherically symmetric potentials consisting of a hard core and a
      linear repulsive ramp. This generic potential has two characteristic length
      scales: the hard and soft core diameters. The family of potentials is generated
      by varying their ratio, lambda. We find negative thermal expansion (thermodynamic
      anomaly) and an increase of the diffusion coefficient upon isothermal compression
      (dynamic anomaly) for 0< or =lambda<6/7. As in water, the regions where these
      anomalies occur are nested domes in the (T, p) or (T, P) planes , with the
      thermodynamic anomaly dome contained entirely within the dynamic anomaly dome. We
      calculate translational and orientational order parameters (t and Q6), and
      project equilibrium state points onto the (t, Q6) plane, or order map. The order
      map evolves from waterlike behavior to hard-sphere-like behavior upon varying
      lambda between 4/7 and 6/7. Thus, we traverse the range of liquid behavior
      encompassed by hard spheres (lanbda=1) and waterlike (lambda approximately 4/7)
      with a family of tunable spherically symmetric potentials by simply varying the
      ratio of hard to soft-core diameters. Although dynamic and thermodynamic
      anomalies occur almost across the entire range 0< or=lambda< or=1, waterlike
      structural anomalies (i.e., decrease in both t and Q6 upon compression and
      strictly correlated T and Q6 in the anomalous region) occur only around
      lambda=4/7. Waterlike anomalies in structure, dynamics and thermodynamics arise
      solely due to the existence of two length scales, with their ratio lambda being
      the single control parameter, orientation-dependent interactions being absent by
      design.

PMID- 16802926
TI  - Ion exchange phase transitions in water-filled channels with charged walls.
AB  - Ion transport through narrow water-filled channels is impeded by a high
      electrostatic barrier. The latter originates from the large ratio of the
      dielectric constants of the water and the surrounding media. We show that
      "doping," i.e., immobile charges attached to the walls of the channel,
      substantially reduces the barrier. This explains why most of the biological ion
      channels are "doped." We show that at rather generic conditions the channels may
      undergo ion exchange phase transitions (typically of the first order). Upon such
      a transition a finite latent concentration of ions may either enter or leave the
      channel, or be exchanged between the ions of different valences. We discuss
      possible implications of these transitions for the Ca-vs-Na selectivity of
      biological Ca channels. We also show that transport of divalent Ca ions is
      assisted by their fractionalization into two separate excitations.

PMID- 16802927
TI  - Structure of plastically compacting granular packings.
AB  - In this paper we present results of structural studies of compacting experimental
      systems of ductile grains in two and three dimensions. The high precision of our
      two-dimensional experiments enables a detailed study of the evolution of
      coordination numbers and local crystalline arrangements as a function of the
      packing fraction. The structure in both dimensions deviates considerably from
      that of hard disks and spheres, although geometrically, crystalline arrangements
      dominate on a local scale (in two dimensions). In three dimensions, the evolution
      of the coordination number is compared to experimental packings of hard and
      ductile grains from the literature. This comparison shows that the evolution of
      coordination number with packing fraction is not unique for ductile systems in
      general, but must depend on rheology and grain size.

PMID- 16802928
TI  - Arching in tapped deposits of hard disks.
AB  - We simulate the tapping of a bed of hard disks in a rectangular box by using a
      pseudodynamic algorithm. In these simulations, arches are unambiguously defined
      and we can analyze their properties as a function of the tapping amplitude. We
      find that an order-disorder transition occurs within a narrow range of tapping
      amplitudes as has been seen by others. Arches are always present in the system
      although they exhibit regular shapes in the ordered regime. Interestingly, an
      increase in the number of arches does not always correspond to a reduction in the
      packing fraction. This is in contrast with what is found in three-dimensional
      systems.

PMID- 16802929
TI  - Granular clustering: self-consistent analysis for general coefficients of
      restitution.
AB  - We study the equilibrium behavior of one-dimensional granular clusters and one
      particle granular gases for a variety of velocity-dependent coefficients of
      restitution r. We obtain equations describing the long-time behavior for the
      cluster's pressure, rms velocity, and granular interspacing. We show that for
      extremely long times, clusters with velocity-dependent coefficients of
      restitution are unstable and dissolve into homogeneous, quasielastic gases, but
      clusters with velocity-independent r are permanent. This is in accordance with
      hydrodynamic studies pointing to the transient nature of density instabilities
      for granular gases with velocity-dependent r.

PMID- 16802930
TI  - Shear strength properties of wet granular materials.
AB  - We investigate shear strength properties of wet granular materials in the
      pendular state (i.e., the state where the liquid phase is discontinuous) as a
      function of water content. Sand and glass beads were wetted and tested in a
      direct shear cell and under various confining pressures. In parallel, we carried
      out three-dimensional molecular dynamics simulations by using an explicit
      equation expressing capillary force as a function of interparticle distance,
      water bridge volume, and surface tension. We show that, due to the peculiar
      features of capillary interactions, the major influence of water content over the
      shear strength stems from the distribution of liquid bonds. This property results
      in shear strength saturation as a function of water content. We arrive at the
      same conclusion by a microscopic analysis of the shear strength. We propose a
      model that accounts for the capillary force, the granular texture, and particle
      size polydispersity. We find fairly good agreement of the theoretical estimate of
      the shear strength with both experimental data and simulations. From numerical
      data, we analyze the connectivity and anisotropy of different classes of liquid
      bonds according to the sign and level of the normal force as well as the bond
      direction. We find that weak compressive bonds are almost isotropically
      distributed whereas strong compressive and tensile bonds have a pronounced
      anisotropy. The probability distribution function of normal forces is
      exponentially decreasing for strong compressive bonds, a decreasing power-law
      function over nearly one decade for weak compressive bonds, and an increasing
      linear function in the range of tensile bonds. These features suggest that
      different bond classes do not play the same role with respect to the shear
      strength.

PMID- 16802931
TI  - Voronoi neighbor statistics of homogeneously sheared inelastic hard disks and
      hard spheres.
AB  - In this work we extend our earlier Voronoi neighbor analysis [J. Chem. Phys. 123,
      074502 (2005)] to homogeneously sheared inelastic hard-particle structures, the
      simplest model for rapid granular matter. The pair distribution function is
      partitioned into the nth neighbor coordination number (Cn), and the nth neighbor
      position distribution [fn(r)]. The distribution of the number of Voronoi faces
      (Pn) is also considered since C1 is its mean. We report the Cn and Pn for the
      homogeneously sheared inelastic hard-disk and hard-sphere structures. These
      statistics are sensitive to shear ordering transition, the nonequilibrium
      analogue of the freezing transition. In the near-elastic limit, the sheared fluid
      statistics approach that of the thermodynamic fluid. On shear ordering, due to
      the onset of order, the Cn for sheared structures approach that of the
      thermodynamic solid phase. The suppression of nucleation by the homogeneous shear
      is evident in these statistics. As inelasticity increases, the shear ordering
      packing fraction increases. Due to the topological instability of the
      isotropically perturbed face-centered cubic lattice, polyhedra with faces 12 to
      18, with a mean at 14, coexist even in the regular close packed limit for the
      thermodynamic hard-sphere solid. In shear ordered inelastic hard-sphere
      structures there is a high incidence of 14-faceted polyhedra and a consequent
      depletion of polyhedra with faces 12, 13, 15-18, due to the formation of body
      centered-tetragonal (bct) structures. These bct structures leave a body-centered
      cubic-like signature in the Cn and Pn data. On shear ordering, close-packed
      layers slide past each other. However, with a velocity-dependent coefficient of
      restitution, at a critical shear rate these layers get disordered or amorphized.
      We find that the critical shear rate for amorphization is inversely proportional
      to the particle diameter, as compared to the inverse square scaling observed in
      dense colloidal suspensions.

PMID- 16802932
TI  - Dynamics of random packings in granular flow.
AB  - We present a multiscale simulation algorithm for amorphous materials, which we
      illustrate and validate in a canonical case of dense granular flow. Our algorithm
      is based on the recently proposed spot model, where particles in a dense random
      packing undergo chainlike collective displacements in response to diffusing
      "spots" of influence, carrying a slight excess of interstitial free volume. We
      reconstruct the microscopic dynamics of particles from the "coarse grained"
      dynamics of spots by introducing a localized particle relaxation step after each
      spot-induced block displacement, simply to enforce packing constraints with a
      (fairly arbitrary) soft-core repulsion. To test the model, we study to what
      extent it can describe the dynamics of up to 135,000 frictional, viscoelastic
      spheres in granular drainage simulated by the discrete-element method (DEM). With
      only five fitting parameters (the radius, volume, diffusivity, drift velocity,
      and injection rate of spots), we find that the spot simulations are able to
      largely reproduce not only the mean flow and diffusion, but also some subtle
      statistics of the flowing packings, such as spatial velocity correlations and
      many-body structural correlations. The spot simulations run over 100 times faster
      than the DEM and demonstrate the possibility of multiscale modeling for amorphous
      materials, whenever a suitable model can be devised for the coarse-grained spot
      dynamics.

PMID- 16802934
TI  - Fluid-mechanical and electrical fluctuation forces in colloids.
AB  - Fluctuations in fluid velocity and fluctuations in electric fields may both give
      rise to forces acting on small particles in colloidal suspensions. Such forces in
      part determine the thermodynamic stability of the colloid. At the classical
      statistical thermodynamic level, the fluid velocity and electric field
      contributions to the forces are comparable in magnitude. When quantum fluctuation
      effects are taken into account, the electric-fluctuation-induced van der Waals
      forces dominate those induced by purely fluid-mechanical motions. The physical
      principles are applied in detail for the case of colloidal particle attraction to
      the walls of the suspension container and more briefly for the case of forces
      between colloidal particles.

PMID- 16802933
TI  - Aggregation in a mixture of Brownian and ballistic wandering particles.
AB  - In this paper, we analyze the scaling properties of a model that has as limiting
      cases the diffusion-limited aggregation (DLA) and the ballistic aggregation (BA)
      models. This model allows us to control the radial and angular scaling of the
      patterns, as well as their gap distributions. The particles added to the cluster
      can follow either ballistic trajectories, with probability Pba, or random ones,
      with probability Prw=1-Pba. The patterns were characterized through several
      quantities, including those related to the radial and angular scaling. The
      fractal dimension as a function of Pba continuously increases from df
      approximately 1.72 (DLA dimensionality) for Pba=0 to df approximately 2 (BA
      dimensionality) for Pba. However, the lacunarity and the active zone width
      exhibit a distinct behavior: they are convex functions of Pba with a maximum at
      Pba approximately 1/2. Through the analysis of the angular correlation function,
      we found that the difference between the radial and angular exponents decreases
      continuously with increasing Pba and rapidly vanishes for Pba>1/2, in agreement
      with recent results concerning the asymptotic scaling of DLA clusters.

PMID- 16802935
TI  - Phenomenological model for a melt-freeze phase of sliding bilayers.
AB  - Simulations show that sliding bilayers of colloidal particles can exhibit a
      phase, the "melt-freeze" phase, where the layers stochastically alternate between
      solidlike and liquidlike states. We introduce a mean field phenomenological model
      with two order parameters to understand the interplay of two adjacent layers
      while the system is in this remarkable phase. Predictions from our numerical
      simulations of a system in the melt-freeze phase include the tendency of two
      adjacent layers to be in opposite states (solid and liquid) and the difference
      between the fluctuation of the order parameter in one layer while the other layer
      is in the same phase compared to the fluctuation while the other layer is in the
      opposite phase. We expect this behavior to be seen in future simulations and
      experiments.

PMID- 16802936
TI  - Entropic forces in dilute colloidal systems.
AB  - Depletion forces can be accounted for by a contraction of the description in the
      framework of the integral equations theory of simple liquids. This approach
      includes, in a natural way, the effects of the concentration on the depletion
      forces, as well as energetic contributions. In this paper we systematically study
      this approach in a large variety of dilute colloidal systems composed of
      spherical and nonspherical hard particles, in two and in three dimensions, in the
      bulk and in front of a hard wall with a relief pattern. We show by this way the
      form in which concentration and geometry determine the entropic interaction
      between colloidal particles. The accuracy of our results is corroborated by
      comparison with computer simulations.

PMID- 16802937
TI  - Static shear modulus of electrorheological fluids.
AB  - We report measurements of the static shear modulus of electrorheological (ER)
      fluids consisting of water-wetted silica microspheres in silicone oil. A shear
      annealing method, using creep-recovery (CR) cycles under an external electric
      field, is used to enhance ER properties of the fluid. The shear-annealing method
      enables the silica spheres in the ER fluid to form better aligned and denser
      column microstructures. A stable state with elastic shear deformation is obtained
      after a sufficient number of CR cycles, with an optimal combination of stress
      duration and shear strength. Static shear modulus is obtained by measuring the
      elastic deformations at different shear stresses for an electric field frequency
      from 10 to 1000 Hz. A water-bridge model is proposed to explain the enhanced
      shear modulus.

PMID- 16802938
TI  - Phase behavior and structure of model colloid-polymer mixtures confined between
      two parallel planar walls.
AB  - Using Gibbs ensemble Monte Carlo simulations and density functional theory we
      investigate the fluid-fluid demixing transition in inhomogeneous colloid-polymer
      mixtures confined between two parallel plates with separation distances between
      one and ten colloid diameters covering the complete range from quasi-two
      dimensional to bulklike behavior. We use the Asakura-Oosawa-Vrij model in which
      colloid-colloid and colloid-polymer interactions are hard-sphere like, while the
      pair potential between polymers vanishes. Two different types of confinement
      induced by a pair of parallel walls are considered--namely, either through two
      hard walls or through two semipermeable walls that repel colloids but allow
      polymers to freely penetrate. For hard (semipermeable) walls we find that the
      capillary binodal is shifted towards higher (lower) polymer fugacities and lower
      (higher) colloid fugacities as compared to the bulk binodal; this implies
      capillary condensation (evaporation) of the colloidal liquid phase in the slit. A
      macroscopic treatment is provided by a symmetric Kelvin equation for general
      binary mixtures based on the proximity in chemical potentials of statepoints at
      capillary coexistence and the reference bulk coexistence. Results for capillary
      binodals compare well with those obtained from the classic version of the Kelvin
      equation due to [Evans and Marini Bettolo Marconi, J. Chem. Phys. 86, 7138
      (1987)] and are quantitatively accurate away from the fluid-fluid critical point,
      even at small wall separations. However, the significant shift of the critical
      polymer fugacity towards higher values upon increasing confinement, as found in
      simulations, is not reproduced. For hard walls the density profiles of polymers
      and colloids inside the slit display oscillations due to packing effects for all
      statepoints. For semipermeable walls either similar structuring or flat profiles
      are found, depending on the statepoint considered.

PMID- 16802939
TI  - Nonlinear dynamics of semiflexible magnetic filaments in an ac magnetic field.
AB  - Flexible spontaneously magnetized filaments exist in the living world
      (magnetotactic bacteria) and arise in magnetic colloids with large magnetodipolar
      interaction parameter. We demonstrate that these filaments possess variety of
      novel nonlinear phenomena in an ac magnetic field: orientation of the filament in
      the direction perpendicular to the field and the development of the oscillating U
      like shapes, which presumably can lead to the formation of rings of magnetic
      filaments. It is found that these phenomena are determined by the development of
      the localized boundary modes of the filament deformation. We have illustrated by
      qualitative estimates that the phenomena found may be useful for insight into the
      complex pattern formation phenomena in ensembles of magnetic particles under the
      action of an ac magnetic field.

PMID- 16802940
TI  - Noise-reduced electroless deposition of arrays of copper filaments.
AB  - We report here a self-organized electroless deposition of copper in an ultrathin
      layer CuSO4 of electrolyte. Microscopically the branching rate of the copper
      deposits is significantly decreased, forming an array of smooth polycrystalline
      filaments. Compared with a conventional electrodeposition system, no macroscopic
      electric field is involved and the thickness of the electrolyte layer is greatly
      decreased. Therefore the electroless deposition takes place in a nearly ideal,
      two-dimensional diffusion-limited environment. We suggest that restriction of the
      thickness of the electrolyte film is responsible for the generation of smoother
      branches of the electrodeposits. Our data also show that even in a diffusion
      limited scenario the aggregate morphology is not necessarily very ramified and
      fractal-like.

PMID- 16802941
TI  - Gap-size distribution functions of a random sequential adsorption model of
      segments on a line.
AB  - We performed extensive simulations accompanied by a detailed study of a two
      segment size random sequential model on the line. We followed the kinetics
      towards the jamming state, but we paid particular attention to the
      characterization of the jamming state structure. In particular, we studied the
      effect of the size ratio on the mean-gap size, the gap-size dispersion, gap-size
      skewness, and gap-size kurtosis at the jamming state. We also analyzed the above
      quantities for the four possible segment-to-segment gap types. We ranged the
      values of the size ratio from one to twenty. In the limit of a size ratio of one,
      one recovers the classical car-parking problem. We observed that at low size
      ratios the jamming state is constituted by short streaks of small and large
      segments, while at high values of the size ratio the jamming state structure is
      formed by long streaks of small segments separated by a single large segment.
      This view of the jamming state structure as a function of the size ratio is
      supported by the various measured quantities. The present work can help provide
      insight, for example, on how to minimize the interparticle distance or minimize
      fluctuations around the mean particle-to-particle distance.

PMID- 16802942
TI  - Strongly anisotropic roughness in surfaces driven by an oblique particle flux.
AB  - Using field theoretic renormalization, an MBE-type growth process with an
      obliquely incident influx of atoms is examined. The projection of the beam on the
      substrate plane selects a "parallel" direction, with rotational invariance
      restricted to the transverse directions. Depending on the behavior of an
      effective anisotropic surface tension, a line of second-order transitions is
      identified, as well as a line of potentially first-order transitions, joined by a
      multicritical point. Near the second-order transitions and the multicritical
      point, the surface roughness is strongly anisotropic. Four different roughness
      exponents are introduced and computed, describing the surface in different
      directions, in real or momentum space. The results presented challenge an earlier
      study of the multicritical point.

PMID- 16802943
TI  - Scaling properties in the average number of attempts until saturation in random
      sequential adsorption processes.
AB  - In the present paper we investigate the exact average number of attempts until
      saturation when a square lattice is ceaselessly bombarded with beta-bell (beta>
      or =1) particles, i.e., linear particles that require beta consecutive lattice
      sites to be adsorbed. When that average number is normalized with the
      corresponding single-particle average, a scale invariant behavior is revealed
      with a scaling exponent alpha=0.017 +/- 0.001, independent of beta (beta>1). The
      scale behavior is suggested by the branching characteristics governing the
      sequential random adsorption of beta-bell (beta>1) particles, which is indeed a
      consequence of configurational correlations.

PMID- 16802944
TI  - Orientational ordering of linear n-alkanes in silicon nanotubes.
AB  - Orientational ordering of short and intermediate -alkanes confined to silicon
      nanotubes has been studied using 1H NMR. The measured residual nuclear dipolar
      couplings characterizing the degree of molecular ordering were found to depend on
      the pore size and the molecular length in a complex way. It is inferred from the
      experimental results that the observed behavior is governed by concomitance of
      surface and intermolecular interactions as well as the effect of confinement.

PMID- 16802945
TI  - Measurements of the three-dimensional shape of ice crystals in supercooled water.
AB  - Experimentally grown ice crystals from ultrapure supercooled water are imaged by
      means of Mach-Zehnder interferometry. By analyzing the fringe patterns the phase
      information and thus the three-dimensional shape of the ice crystals is recovered
      quantitatively. The integral parameters height of the basal plane, volume, and
      surface of the crystals are measured as a function of time and supercooling. It
      is found that all measured parameters follow a power law as a function of time
      and the exponents are found to be independent of the supercooling. The shape
      transition from the prismatic to the basal face along the main growth direction
      of the ice dendrites as a function of the distance from the tip is found to be a
      power law as well. Our findings support the validity of universal growth laws in
      pattern forming systems.

PMID- 16802946
TI  - Domain growth dynamics and local viscosity in stratifying foam films.
AB  - We present a quantitative theory and experiments for the expansion dynamics of
      domains in stratifying foam films. Foam films containing micelles, colloidal
      particles or polymer-surfactant complexes often form layered structures and thin
      in a stepwise fashion: circular domains of lower thickness are formed and expand
      following a R(t) proportional variant t1/2 law. In the present paper the film is
      modeled by an incompressible three-dimensional fluid with incompressible
      surfaces. The film tension difference between the film and domains results in the
      formation of a rim at the domain boundary and a gradient in film thickness and
      pressure in the surrounding film. The material transport due to this gradient
      lets the domains grow. We present experiments utilizing the thin balance method
      to qualitatively confirm the thinning mechanism and to determine material
      parameters including local film viscosity of a film composed of 4400 ppm
      acrylamide/acrylamidomethylpropanesulfonate-copolymer and 0.006 mmol/l
      dodecyltrimethylammonium bromide solution. We found a film viscosity of about 60
      times the bulk viscosity, consistent with previous measurement in the same system
      but using another method.

PMID- 16802947
TI  - Growth of a collapsing Langmuir monolayer.
AB  - Langmuir monolayers of stearic acid on Co ions in the aqueous subphase have been
      deposited at different stages of constant pressure collapse, on hydrophilic
      Si(001) using a modified version of the inverse Langmuir-Schaefer method of
      horizontal deposition. The electron density profiles (EDPs) along the depth of
      the deposited films, extracted from the x-ray reflectivity data, show that a
      monolayer to bi-molecular layer transformation takes place after collapse. The
      molecules in the lower monolayer have asymmetric configurations with head groups
      touching water and tails in air, whereas molecules in the upper layer are in
      symmetric configurations with tails on both sides of the heads. Atomic force
      microscopy images of the deposited films after collapse, however, show nearly
      circular islands of height more than that of the bimolecular layer observed in
      the EDP. As pressure increases, ridges are seen to coexist with these islands.
      Although the coverage of such islands and ridges is low, they play an important
      role in determining the growth mode. The growth of the wetting and island layers,
      taken together, has a striking similarity with the Stranski-Krastanow mode,
      observed usually for heteroepitaxial growth.

PMID- 16802948
TI  - Ferroelectricity of a bent-core material with cholesteryl terminal chain.
AB  - We have studied the phase sequence and physical properties of an asymmetric bent
      core material with a chiral rigid cholesteryl moiety, and a flexible achiral
      alkyl side chain at the other end. The combination of the achiral bent core with
      the chiral cholesteryl unit results in properties different from those of both
      the usual calamitic and bent-core materials. We find that the presence of the
      bent core unit induces a wide-temperature-range optically isotropic (probably
      BPIII) mesophase between the isotropic and cholesteric (chiral nematic) phases.
      Below the cholesteric phase a ferroelectric smectic-C* structure occurs in which
      the bent-core units do not seem to form a polar close packing.

PMID- 16802949
TI  - Orientational order and dynamics of the dendritic liquid crystal organo-siloxane
      tetrapodes determined using dielectric spectroscopy.
AB  - The dielectric measurements have been carried out on the two zeroth generation
      dendrimers with four branched arms (called tetrapodes) based on the siloxane
      cores. The results are analyzed in the framework of the molecular theory of
      dielectric permittivity by Maier and Meier for nematogens. At least four
      molecular processes are resolved in the dielectric relaxation spectra in the
      nematic phase for each of the two tetrapodes. Three of them are assigned to the
      reorientation of the monomeric unit whereas the fourth is assigned to the
      rotation of the molecular segments in the individual arms of the monomeric unit
      around the long molecular axis. The dielectric relaxation strength of the low
      frequency process has been used to calculate the orientational order parameter.
      The dynamics of the resolved processes has been quantitatively analyzed using the
      results of the microscopic model of the rotational diffusion, given by Coffey and
      Kalmykov [W. T. Coffey and Yu. P. Kalmykov, Adv. Chem. Phys. 113, 487 (2000)]
      using the calculated order parameter. All molecular processes: the rotation
      around the short molecular axis (end-over-end rotation), precession around the
      director and the rotation around the long molecular axis (also called the
      spinning motion) are shown to have successfully been reproduced by the model. The
      anisotropy of the rotational diffusion coefficients gradually increases with a
      reduction in temperature, to a factor of 3 in the nematic phase relative to its
      isotropic phase.

PMID- 16802950
TI  - Molecular self-organization in cylindrical nanocavities.
AB  - We studied molecular organization in cylindrical nanocavities using liquid
      crystals. NMR analysis shows high surface-induced ordering way above the bulk
      critical temperature. The surface-order evolution reveals replacement of the
      isotropic phase by a paranematic phase and surface-induced disordering in the
      nematic phase. Due to strong surface potential and nanoconfinement, complete
      wetting and continuous evolution of the surface-order parameter are observed
      through the nematic-paranematic transition. As we show, the counter-intuitive
      absence of complete phase transition at the interface while an abrupt phase
      transition was measured in the averaged order parameter is in good agreement with
      established theories.

PMID- 16802951
TI  - Stochastic molecular motions in the nematic, smectic-A, and solid phases of p,p'
      di-n-heptyl-azoxybenzene as seen by quasielastic neutron scattering and 13C cross
      polarization magic-angle-spinning NMR.
AB  - Molecular rotational dynamics in p,p'-di-n-heptyl-azoxybenzene was studied by
      means of quasielastic neutron scattering (QENS) and 13C cross-polarization magic
      angle-spinning (CPMAS) NMR. Fast reorientation of the hydrogen nuclei was
      observed by QENS in the two liquid crystalline (LC) phases nematic and smectic A,
      as well as in the crystalline phase. The latter could not be restricted to the 
      CH3 rotations alone, and a clear indication was found of some other reorientation
      motions persisting in the crystal. Two Lorentz-type components convoluted with
      the resolution function gave an excellent fit to the QENS spectra in both LC
      phases. The narrow (slow) component was attributed to the reorientation of the
      whole molecule around the long axis. The corresponding characteristic time of
      approximately 130 ps agreed well with the values obtained in recent dielectric
      relaxation and 2H NMR studies. The full width at half maximum of the broader
      (fast) component shows a quadratic Q dependence (Q is the momentum transfer).
      Hence the corresponding motions could be described by a stretched exponential
      correlation function and were interpreted as various "crankshaft-type" motions
      within the alkyl tails. The 13C CPMAS experiments fully corroborated the QENS
      results, sometimes considered ambiguous in complex systems.

PMID- 16802952
TI  - Textural transformations in islands on free standing smectic-C* liquid crystal
      films.
AB  - We report on and analyze the textural transformations in islands, thicker
      circular domains, floating in very thin free standing chiral Smectic-C* liquid
      crystal films. As an island is growing, an initial pure bend texture of the
      director changes into a reversing spiral at a critical size. Another distinct
      spiral texture is induced by changing the boundary condition at the central point
      defect in the island. To understand these transformations from a pure bend
      island, a linear stability analysis of the c-director free energy is developed,
      which predicts a state diagram for the island. Our observations are consistent
      with the theoretical phase diagram.

PMID- 16802953
TI  - Nematic membranes: shape instabilities of closed achiral vesicles.
AB  - We consider the coupling between the local curvature tensor of a membrane and the
      local two-dimensional nematic order parameter, deriving it from a quasi
      microscopic argument. This coupling makes the nematic director aligned along the
      lowest curvature eigenvector in a local metric. Local bending of a membrane may
      then generate nematic ordering. Alternatively, emerging nematic order leads to
      shape instabilities of closed vesicles. The theory is applied to a spherical
      isotropic vesicle, which turns into a prolate shape with two +1 disclinations on
      its poles as the nematic order sets in the membrane, described within the Landau
      de Gennes continuum model.

PMID- 16802954
TI  - Light-induced rotation of dye-doped liquid crystal droplets.
AB  - We investigate both theoretically and experimentally the rotational dynamics of
      micrometric droplets of dye-doped and pure liquid crystal induced by circularly
      and elliptically polarized laser light. The droplets are dispersed in water and
      trapped in the focus of the laser beam. Since the optical torque acting on the
      molecular director is known to be strongly enhanced in light-absorbing dye-doped
      materials, the question arises whether a similar enhancement takes place also for
      the overall optical torque acting on the whole droplets. We searched for such
      enhancement by measuring and comparing the rotation speed of dye-doped droplets
      induced by a laser beam having a wavelength either inside or outside the dye
      absorption band, and also comparing it with the rotation of pure liquid crystal
      droplets. No enhancement was found, confirming that photoinduced dye effects are
      only associated with an internal exchange of angular momentum between
      orientational and translational degrees of freedom of matter. Our result provides
      also direct experimental proof of the existence of a photoinduced stress tensor
      in the illuminated dye-doped liquid crystal. Finally, peculiar photoinduced
      dynamical effects are predicted to occur in droplets in which the molecular
      director is not rigidly locked to the flow, but so far they could not be
      observed.

PMID- 16802955
TI  - Lateral and normal forces between patterned substrates induced by nematic
      fluctuations.
AB  - We consider a nematic liquid crystal confined by two parallel flat substrates
      whose anchoring conditions vary periodically in one lateral direction. Within the
      Gaussian approximation, we study the effective forces between the patterned
      substrates induced by the thermal fluctuations of the nematic director. The shear
      force oscillates as a function of the lateral shift between the patterns on the
      lower and the upper substrates. We compare the strength of this fluctuation
      induced lateral force with the lateral van der Waals force arising from
      chemically structured adsorbed monolayers. The fluctuation-induced force in the
      normal direction is either repulsive or attractive, depending on the model
      parameters.

PMID- 16802956
TI  - Universal mean-field phase diagram for biaxial nematics obtained from a minimax
      principle.
AB  - We study a class of quadratic Hamiltonians which describe both fully attractive
      and partly repulsive molecular interactions, characteristic of biaxial liquid
      crystal molecules. To treat the partly repulsive interactions we establish a
      minimax principle for the associated mean-field free energy. We show that the
      phase diagram described by Sonnet [Phys. Rev. E 67, 061701 (2003)] is universal.
      Our predictions are in good agreement with the recent observations on both V
      shaped and tetrapodal molecules.

PMID- 16802957
TI  - Exact solution for a one-dimensional model for reptation.
AB  - We discuss the exact solution for the properties of the recently introduced
      "necklace" model for reptation. The solution gives the drift velocity, diffusion
      constant, and renewal time for asymptotically long chains. Its properties are
      also related to a special case of the Rubinstein-Duke model in one dimension.

PMID- 16802958
TI  - Corrections to scaling in multicomponent polymer solutions.
AB  - We calculate the correction-to-scaling exponent omegaT that characterizes the
      approach to the scaling limit in multicomponent polymer solutions. A direct Monte
      Carlo determination of omegaT in a system of interacting self-avoiding walks
      gives omegaT=0.415+/-0.020. A field-theory analysis based on five- and six-loop
      perturbative series leads to omegaT=0.41+/-0.04. We also verify the
      renormalization-group predictions for the scaling behavior close to the ideal
      mixing point.

PMID- 16802959
TI  - Surface transition in athermal polymer solutions.
AB  - According to a recently developed density functional theory, athermal polymer
      solutions, in which the solvent particles are smaller than the monomers, may
      undergo a bulk fluid-fluid phase separation, driven by excluded volume effects.
      In recent work, we showed that an inert surface immersed in the dilute polymer
      phase can, in principle, be wetted by the condensed phase. However, we show here
      that the "prewetting transition" we assumed in our earlier studies is in fact a
      different type of surface transition. Rather than completely wet the surface at
      coexistence, the condensed phase layer which forms in the presence of the dilute
      bulk remains globally stable (and is finite in width) even as the bulk
      coexistence conditions are approached. Hence, the adsorbed phase inhibits
      complete wetting of the surface by the dilute phase. The surface transition is
      first order for the systems we study here and, for longer polymers, the surface
      phase coexistence line meets the bulk coexistence curve nontangentially to give
      rise to a lower transition point. For short polymers, we find that the surface
      transition can occur for a supercritical bulk. We develop a simple one-component
      thermal model, which displays analogous behavior at an adsorbing surface and
      provides us with some insight into the qualitative mechanisms responsible.

PMID- 16802960
TI  - Stability of toroid and rodlike globular structures of a single stiff-chain
      macromolecule for different bending potentials.
AB  - We study the effect of the bending potential on the stability of toroidal and
      rodlike globules which are typical collapsed conformations of a single stiff
      chain macromolecule. We perform numerical calculations in the framework of the
      bead-stick model of a polymer chain. The intrinsic structure of globules is also
      analyzed. It was shown that the bending potential affects the packing geometry of
      bundles in a toroidal globule in the ground state. This potential also influences
      the bends at the ends of a rodlike globule: both the shape of the loops and the
      number of bonds in each loop have been investigated numerically as well as by
      Monte Carlo computer simulations performed for a separate loop. Our main results
      are (1) the shape of the bending potential could be possibly seen from the
      geometry of a globule; (2) toroidal globules are always more favorable than the
      rodlike ones.

PMID- 16802961
TI  - Multiscale dynamics of biological cells with chemotactic interactions: from a
      discrete stochastic model to a continuous description.
AB  - The cellular Potts model (CPM) has been used for simulating various biological
      phenomena such as differential adhesion, fruiting body formation of the slime
      mold Dictyostelium discoideum, angiogenesis, cancer invasion, chondrogenesis in
      embryonic vertebrate limbs, and many others. We derive a continuous limit of a
      discrete one-dimensional CPM with the chemotactic interactions between cells in
      the form of a Fokker-Planck equation for the evolution of the cell probability
      density function. This equation is then reduced to the classical macroscopic
      Keller-Segel model. In particular, all coefficients of the Keller-Segel model are
      obtained from parameters of the CPM. Theoretical results are verified numerically
      by comparing Monte Carlo simulations for the CPM with numerics for the Keller
      Segel model.

PMID- 16802962
TI  - Healing length and bubble formation in DNA.
AB  - It has been suggested that thermally induced separations ("bubbles") of the DNA
      double-strand may play a role in the initiation of gene transcription, and an
      accurate understanding of the sequence dependence of thermal strand separation is
      therefore desirable. Based on the Peyrard-Bishop-Dauxois model, we show here that
      the bubble forming ability of DNA can be quantified in terms of a healing length
      L(n), defined as the length (number of base-pairs) over which a base-pair defect
      affects bubbles involving n consecutive base-pairs. The probability for a bubble
      of size n is demonstrated to be proportional to the number of adenine-thymine
      base-pairs found within this length. The method for calculating bubble
      probabilities in a given sequence derived from this notion requires several order
      of magnitude less numerical effort than direct evaluation.

PMID- 16802963
TI  - Reconstructing DNA replication kinetics from small DNA fragments.
AB  - In higher organisms, DNA replicates simultaneously from many origins. Recent in
      vitro experiments have yielded large amounts of data on the state of replication
      of DNA fragments. From measurements of the time dependence of the average size of
      replicated and nonreplicated domains, one can estimate the rate of initiation of
      DNA replication origins, as well as the average rate at which DNA bases are
      copied. One problem in making such estimates is that, in the experiments, the DNA
      is broken up into small fragments, whose finite size can bias downward the
      measured averages. Here, we present a systematic way of accounting for this bias
      by deriving theoretical relationships between the original domain-length
      distributions and fragment-domain length distributions. We also derive unbiased
      average-domain-length estimators that yield accurate results, even in cases where
      the replicated (or nonreplicated) domains are larger than the average DNA
      fragment. Then we apply these estimators to previously obtained experimental data
      to extract improved estimates of replication kinetics parameters.

PMID- 16802964
TI  - Vesicle-to-micelle transition in aqueous solutions of amphiphilic calixarene
      derivatives.
AB  - Structure and conformation of spontaneous self-assembled calix[8]arenes
      derivatives are studied by means of static and dynamic light scattering and
      electrophoretic mobility. These amphiphilic molecules are in the aggregated form
      in aqueous solution, in a wide range of pH; they take a vesicle structure in
      neutral and basic pH environment, but, in relatively strong acidic conditions
      (below pH=4.5), a transition from vesicle to micelle occurs. The structural
      change is driven by the surface charge density. At neutral pH calix[8]arenes take
      a negative surface charge, which prevents coagulation and ensures stability; at
      acidic pH the surface charge tend to become positive because of the protonation
      of the hydrophilic head. These pH-responsive aggregates, able to release an
      encapsulated hydrophilic guest, are promising systems for application as
      nanocarriers.

PMID- 16802965
TI  - Hydration dependence of the mass fractal dimension and anomalous diffusion of
      vibrational energy in proteins.
AB  - Vibrational dynamics of proteins and energy flow depend on protein geometry as
      well as interactions of a protein molecule with the surrounding solvent. We
      compute the mass fractal dimension D of proteins ranging from 100 to over 10,000
      amino acids comparing values for the bare protein with those computed when buried
      and hydration waters are included in the calculation. Including water in the
      calculation increases D by about 0.3 to 2.87 on average above D computed for the
      dehydrated protein. The mass fractal dimension of proteins that are partially
      unfolded by molecular dynamics (MD) simulation is also computed and found to vary
      little when the radius of gyration changes within about 10% of that for the
      Protein Data Bank structure. MD simulations of vibrational energy diffusion in
      proteins reveal that the exponent characterizing anomalous diffusion of
      vibrational energy does not change much with hydration, which is seen to be due
      to an increase in the spectral dimension with hydration by a factor similar to
      the increase in D.

PMID- 16802966
TI  - Growth of cortical neuronal network in vitro: modeling and analysis.
AB  - We present a detailed analysis and theoretical growth models to account for
      recent experimental data on the growth of cortical neuronal networks in vitro
      [Phys. Rev. Lett. 93, 088101 (2004)]. The experimentally observed synchronized
      firing frequency of a well-connected neuronal network is shown to be proportional
      to the mean network connectivity. The growth of the network is consistent with
      the model of an early enhanced growth of connection, but followed by a retarded
      growth once the synchronized cluster is formed. Microscopic models with dominant
      excluded volume interactions are consistent with the observed exponential decay
      of the mean connection probability as a function of the mean network
      connectivity. The biological implications of the growth model are also discussed.

PMID- 16802967
TI  - Persistent dynamic attractors in activity patterns of cultured neuronal networks.
AB  - Three remarkable features of the nervous system--complex spatiotemporal patterns,
      oscillations, and persistent activity--are fundamental to such diverse functions
      as stereotypical motor behavior, working memory, and awareness. Here we report
      that cultured cortical networks spontaneously generate a hierarchical structure
      of periodic activity with a strongly stereotyped population-wide spatiotemporal
      structure demonstrating all three fundamental properties in a recurring pattern.
      During these "superbursts," the firing sequence of the culture periodically
      converges to a dynamic attractor orbit. Precursors of oscillations and persistent
      activity have previously been reported as intrinsic properties of the neurons.
      However, complex spatiotemporal patterns that are coordinated in a large
      population of neurons and persist over several hours--and thus are capable of
      representing and preserving information--cannot be explained by known oscillatory
      properties of isolated neurons. Instead, the complexity of the observed
      spatiotemporal patterns implies large-scale self-organization of neurons
      interacting in a precise temporal order even in vitro, in cultures usually
      considered to have random connectivity.

PMID- 16802968
TI  - From spiking neurons to rate models: a cascade model as an approximation to
      spiking neuron models with refractoriness.
AB  - A neuron that is stimulated repeatedly by the same time-dependent stimulus
      exhibits slightly different spike timing at each trial. We compared the exact
      solution of the time-dependent firing rate for a stochastically spiking neuron
      model with refractoriness (spike response model) with that of an inhomogeneous
      Poisson process subject to the same stimulus. To arrive at a mapping between the
      two models we used alternatively (i) a systematic parameter-free Volterra
      expansion of the exact solution or (ii) a linear filter combined with nonlinear
      Poisson rate model (linear-nonlinear Poisson cascade model) with a single free
      parameter. Both the cascade model and the second-order Volterra model showed
      excellent agreement with the exact rate dynamics of the spiking neuron model with
      refractoriness even for strong and rapidly changing input. Cascade rate models
      are widely used in systems neuroscience. Our method could help to connect
      experimental rate measurements to the theory of spiking neurons.

PMID- 16802969
TI  - Brownian dynamics simulation of directional sliding of histone octamers caused by
      DNA bending.
AB  - Chromatin-remodeling complexes such as SWI/SNF and RSC of yeast can perturb the
      structure of nucleosomes in an ATP-dependent manner. Experimental results prove
      that this chromatin remodeling process involves DNA bending. We simulate the
      effect of DNA bending, caused by chromatin-remodeling complexes, on directional
      sliding of histone octamers by Brownian dynamics simulation. The simulation
      results show that, after a DNA loop being generated at the side of a nucleosome,
      the histone octamer slides towards this DNA loop until the loop disappears. The
      DNA loop size is an important factor affecting the process of directional sliding
      of the histone octamer.

PMID- 16802970
TI  - Scaling laws at the phase transition of systems with divergent order parameter
      and/or internal length: the example of DNA denaturation.
AB  - We used the transfer-integral method to compute, with an uncertainty smaller than
      5%, the six fundamental characteristic exponents of two dynamical models for DNA
      thermal denaturation and investigate the validity of the scaling laws. Doubts
      concerning this point arise because the investigated systems (i) have a divergent
      internal length, (ii) are described by a divergent order parameter, and (iii) are
      of dimension 1. We found that the assumption that the free energy can be
      described by a single homogeneous function is robust, despite the divergence of
      the order parameter, so that Rushbrooke's and Widom's identities are valid
      relations. Josephson's identity is instead not satisfied. This is probably due to
      the divergence of the internal length, which invalidates the assumption that the
      correlation length is solely responsible for singular contributions to
      thermodynamic quantities. Fisher's identity is even more wrong. We showed that
      this is due to the d=1 dimensionality and obtained an alternative law, which is
      well satisfied at DNA thermal denaturation.

PMID- 16802971
TI  - Model of low-pass filtering of local field potentials in brain tissue.
AB  - Local field potentials (LFPs) are routinely measured experimentally in brain
      tissue, and exhibit strong low-pass frequency filtering properties, with high
      frequencies (such as action potentials) being visible only at very short
      distances (approximately 10 microm) from the recording electrode. Understanding
      this filtering is crucial to relate LFP signals with neuronal activity, but not
      much is known about the exact mechanisms underlying this low-pass filtering. In
      this paper, we investigate a possible biophysical mechanism for the low-pass
      filtering properties of LFPs. We investigate the propagation of electric fields
      and its frequency dependence close to the current source, i.e., at length scales
      in the order of average interneuronal distances. We take into account the
      presence of a high density of cellular membranes around current sources, such as
      glial cells. By considering them as passive cells, we show that under the
      influence of the electric source field, they respond by polarization. Because of
      the finite velocity of ionic charge movements, this polarization will not be
      instantaneous. Consequently, the induced electric field will be frequency
      dependent, and much reduced for high frequencies. Our model establishes that this
      situation is analogous to an equivalent RC circuit, or better yet a system of
      coupled RC circuits. We present a number of numerical simulations of an induced
      electric field for biologically realistic values of parameters, and show the
      frequency filtering effect as well as the attenuation of extracellular potentials
      with distance. We suggest that induced electric fields in passive cells
      surrounding neurons are the physical origin of frequency filtering properties of
      LFPs. Experimentally testable predictions are provided allowing us to verify the
      validity of this model.

PMID- 16802972
TI  - Application of a random network with a variable geometry of links to the kinetics
      of drug elimination in healthy and diseased livers.
AB  - This paper discusses an application of a random network with a variable number of
      links and traps to the elimination of drug molecules from the body by the liver.
      The nodes and links represent the transport vessels, and the traps represent
      liver cells with metabolic enzymes that eliminate drug molecules. By varying the
      number and configuration of links and nodes, different disease states of the
      liver related to vascular damage have been simulated, and the effects on the rate
      of elimination of a drug have been investigated. Results of numerical simulations
      show the prevalence of exponential decay curves with rates that depend on the
      concentration of links. In the case of fractal lattices at the percolation
      threshold, we find that the decay of the concentration is described by
      exponential functions for high trap concentrations but transitions to stretched
      exponential behavior at low trap concentrations.

PMID- 16802973
TI  - Identifying interactions in mixed and noisy complex systems.
AB  - We present a technique that identifies truly interacting subsystems of a complex
      system from multichannel data if the recordings are an unknown linear and
      instantaneous mixture of the true sources. The method is valid for arbitrary
      noise structure. For this, a blind source separation technique is proposed that
      diagonalizes antisymmetrized cross-correlation or cross-spectral matrices. The
      resulting decomposition finds truly interacting subsystems blindly and suppresses
      any spurious interaction stemming from the mixture. The usefulness of this
      interacting source analysis is demonstrated in simulations and for real
      electroencephalography data.

PMID- 16802974
TI  - Harmonic generation by yeast cells in response to low-frequency electric fields.
AB  - We report on harmonic generation by budding yeast cells (Saccharomyces
      cerevisiae, 10(8) cells/ml) in response to sinusoidal electric fields with
      amplitudes ranging from zero to 5 V/cm in the frequency range 10-300 Hz. The cell
      generated harmonics are found to exhibit strong amplitude and frequency
      dependence. Sodium metavanadate, an inhibitor of the proton pump known as H+
      ATPase, and glucose, a substrate of H+-ATPase, are found to increase harmonic
      production at low amplitudes while reducing it at large amplitudes. This P-type
      proton pump can be driven by an oscillatory transmembrane potential, and its
      nonlinear response is believed to be largely responsible for harmonic production
      at low frequencies in yeast cells. We find that the observed harmonics show
      dramatic changes with time and in their field and frequency dependence after
      perturbing the system by adding an inhibitor, substrate, or membrane depolarizer
      to the cell suspension.

PMID- 16802975
TI  - Effect of external fluctuations on the affinity-specificity negative correlation
      in DNA-probe interactions.
AB  - We show that the site-specific interaction of a probe DNA with the template DNA
      can be well modeled as an unbiased random jump process, where the probe molecule
      first nonspecifically binds to the template DNA and then searches for the
      specific site via unbiased random jump motion on the template DNA. By
      investigating the effects of increasing the jump size, and the fluctuations in
      the position of the specific site and the fluctuations in the specific site
      interval on the affinity-specificity negative correlation, we show that (1)
      increasing the jump size will in turn increase the affinity of the probe toward
      its target site on the template DNA, however, with a limiting value--the maximum
      affinity condition; (2) the degree of supercoiling or condensation of the
      template DNA as well as the electrostatic interactions between the probe and the
      template in turn control the jump size associated with the dynamics of the probe
      on the template DNA; (3) under a maximum specificity condition (therefore with
      minimum affinity), by introducing an external fluctuation in the relative
      position of the target site on the template DNA with respect to the probe, one
      can still improve the affinity rate; (4) on the other hand, one can improve the
      specificity of the probe toward the target site on the template DNA by
      introducing external fluctuations in the target-site interval. Finally, we
      propose the design strategies and optimum experimental conditions to
      simultaneously enhance the affinity as well as the specificity of probe toward
      its target site on the template DNA.

PMID- 16802976
TI  - Nonlinear dynamics and self-organization of rotary molecular motor ensembles.
AB  - The coupled nonlinear dynamics of rotary motor ensembles and an embedding fluid
      medium are simulated on the basis of Navier-Stokes equations. The model
      description considers space-dependent rotation of motors and a spatially
      inhomogeneous motor distribution as well as spatial fluctuations in molecular
      properties. The mutual influence of motor rotations and fluid dynamics as well as
      spatial inhomogeneities of their molecular properties are self-consistently
      included. Space-time simulations visualize the complex interplay between the
      fluid dynamics and motor rotation and show that the dynamic coupling to the
      environment via the velocity field as well as the spatial inhomogeneity and
      distribution of rotors determines the overall behavior of the motor complex.
      Depending on the initial molecular distribution, rotation frequency, and fluid
      dynamics a spatial self-organization or a chaotic behavior may arise.

PMID- 16802977
TI  - Empirical mode decomposition and synchrogram approach to cardiorespiratory
      synchronization.
AB  - We use the empirical mode decomposition method to decompose experimental
      respiratory signals into a set of intrinsic mode functions (IMFs), and consider
      one of these IMFs as a respiratory rhythm. We then use the Hilbert spectral
      analysis to calculate the instantaneous phase of the IMF. Heartbeat data are
      finally incorporated to construct the cardiorespiratory synchrogram, which is a
      visual tool for inspecting synchronization. We perform analysis on 20 data sets
      collected by the Harvard medical school from ten young (21-34 years old) and ten
      elderly (68-81 years old) rigorously screened healthy subjects. Our results
      support the existence of cardiorespiratory synchronization. We also investigate
      the origin of the cardiorespiratory synchronization by addressing the problem of
      correlations between regularities of respiratory and cardiac signals. Our
      analysis shows that regularity of respiratory signals plays a dominant role in
      the cardiorespiratory synchronization.

PMID- 16802978
TI  - Multielectrode electroencephalogram power spectra: theory and application to
      approximate correction of volume conduction effects.
AB  - Using a physiologically based model of brain activity, electroencephalogram (EEG)
      power spectra are calculated for signals derived from general linear combinations
      of voltages from multiple electrodes, with and without filtering by volume
      conduction. Two simple methods of combining scalp measurements to estimate
      unfiltered EEG power spectra are then proposed and their accuracy and robustness
      are explored, using the model predictions as an illustration. It is found that
      these methods, including a case that uses just three electrodes, enable improved
      estimation of the underlying spectrum relative to each of several widely used
      combinations alone.

PMID- 16802979
TI  - Paradox of simple limiter control.
AB  - Chaos control by simple limiters is an easy-to-implement and effective method of
      stabilizing irregular fluctuations. Here we show that applying limiter control to
      a state variable can significantly shift its mean value. In many situations, this
      is a countereffective as well as unexpected result, when the aim of control is
      also to restrict the dynamics. We discuss this effect on the basis of a model of
      population dynamics and conclude that it can have severe implications for the
      management of pest species and epidemic spread.

PMID- 16802980
TI  - Dynamical complexity detection in short-term physiological series using base
      scale entropy.
AB  - Physiological systems generate complex fluctuations in their output signals that
      reflect the underlying dynamics. The base-scale entropy method was proposed as a
      complexity measure to investigate the complexity of time series. The advantages
      of this method are simplicity and extremely fast calculation for very short data
      sets. This method enables analyzing very short, nonstationary, and noisy data
      sets. We employed this method for short-term physiological time series for
      analysis of heart-rate variability signals. The results show that the simple and
      easily calculated measure can effectively detect the complexity dissimilarity of
      physiological time series in different physiological or pathological states,
      which is convenient for clinical applications.

PMID- 16802981
TI  - Dielectric dispersion of erythrocyte ghosts.
AB  - The underlying mechanism of the low-frequency dielectric dispersion, called the
      alpha dispersion, of osmotically lysed erythrocytes (erythrocyte ghosts) has
      remained open since its finding [H. P. Schwan and E. L. Carstensen, Science 125,
      985 (1957)]. The alpha dispersion is peculiar to erythrocyte ghosts and has never
      been observed for intact erythrocytes. Numerical calculation based on interfacial
      polarization revealed that the alpha dispersion is due to the presence of a hole
      of about 30 nm in radius in the plasma membrane.

PMID- 16802982
TI  - Partition functions and finite-size scalings of Ising model on helical tori.
AB  - The exact closed forms of the partition functions of a two-dimensional Ising
      model on square lattices with twisted boundary conditions are given. The
      constructions of helical tori are unambiguously related to the twisted boundary
      conditions by virtue of the SL(2, Z) transforms. The numerical analyses on the
      deviations of the specific-heat peaks away from the bulk critical temperature
      reveal that the finite-size effect of herical tori is independent of the
      chirality.

PMID- 16802983
TI  - Correlation and response in a driven dissipative model.
AB  - We consider a simple dissipative system with spatial structure in contact with a
      heat bath. The system always exhibits correlations except in the cases of zero
      and maximal dissipation. We explicitly calculate the correlation function and the
      nonlocal response function of the system and show that they have the same spatial
      dependence.

PMID- 16802984
TI  - Frequency versus relaxation oscillations in a semiconductor laser with coherent
      filtered optical feedback.
AB  - We investigate the dynamics of a semiconductor laser subject to coherent delayed
      filtered optical feedback. A systematic bifurcation analysis reveals that this
      system supports two fundamentally different types of oscillations, namely
      relaxation oscillations and external roundtrip oscillations. Both occur stably in
      large domains under variation of the feedback conditions, where the feedback
      phase is identified as a key quantity for controlling this dynamical complexity.
      We identify two separate parameter regions of stable roundtrip oscillations,
      which occur throughout in the form of pure frequency oscillations.

PMID- 16802985
TI  - Universal behavior in populations composed of excitable and self-oscillatory
      elements.
AB  - We study the robustness of self-sustained oscillatory activity in a globally
      coupled ensemble of excitable and oscillatory units. The critical balance to
      achieve collective self-sustained oscillations is analytically established. We
      also report a universal scaling function for the ensemble's mean frequency. Our
      results extend the framework of the "aging transition" [Phys. Rev. Lett. 93,
      104101 (2004)] including a broad class of dynamical systems potentially relevant
      in biology.

PMID- 16802986
TI  - Photoacoustic study of relaxation dynamics in multibubble systems in laser
      superheated water.
AB  - Microsecond relaxation dynamics in a cavitating surface layer of bulk water
      superheated by a TEA CO(2) laser was studied using contact broadband
      photoacoustic spectroscopy. Damped nanosecond and microsecond oscillatory
      pressure-tension cycles recorded by an acoustic transducer are related to
      oscillations of steam bubbles of different sizes exhibiting strong dissipative
      losses and collective (coalescence and percolation) phenomena. These measurements
      also give important insight into basic parameters, characteristic spatial and
      temporal scales, and the mechanism of laser ablation of absorbing liquids in the
      thermal confinement regime.

PMID- 16802987
TI  - Grid states and nonlinear selection in parametrically excited surface waves.
AB  - Interacting surface waves, parametrically excited by two commensurate frequencies
      (Faraday waves), yield a rich family of nonlinear states, which result from a
      variety of three-wave resonant interactions. By perturbing the system with a
      third frequency, we selectively favor different nonlinear wave interactions.
      Where quadratic nonlinearities are dominant, the only observed patterns
      correspond to "grid" states. Grid states are superlattices in which two corotated
      sets of critical wave vectors are spanned by a sublattice whose basis states are
      linearly stable modes. Specific driving phase combinations govern the selection
      of different grid states.

PMID- 16802988
TI  - Elliptic model for space-time correlations in turbulent shear flows.
AB  - An elliptic model for space-time correlations in turbulent shear flows is
      proposed based on a second order approximation to the iso-correlation contours,
      while Taylor's hypothesis implies a first-order approximation. It is shown that
      the space-time correlations are mainly determined by their space correlations and
      the convection and sweeping velocities. This model accommodates two extreme
      cases: Taylor's hypothesis at vanishing sweeping velocity and the sweeping
      hypothesis at vanishing convection velocity. The result is supported by the data
      from the direct numerical simulation of turbulent channel flows.

PMID- 16802989
TI  - Fully nonlinear evolution of a cylindrical vortex sheet in incompressible
      Richtmyer-Meshkov instability.
AB  - Fully nonlinear motion of a circular interface in incompressible Richtmyer
      Meshkov instability is investigated by treating it as a nonuniform vortex sheet
      between two different fluids. There are many features in cylindrical geometry
      such as the existence of two independent spatial scales, radius and wavelength,
      and the ingoing and outgoing growth of bubbles and spikes. Geometrical
      complexities lead to the results that nonlinear dynamics of the vortex sheet is
      determined from the inward and outward motion rather than bubbles and spikes, and
      that the nonlinear growth strongly depends on mode number.

PMID- 16802990
TI  - Stabilization of vector soliton complexes in nonlocal nonlinear media.
AB  - We introduce vector soliton complexes in nonlocal Kerr-type nonlinear media. We
      discover that under proper conditions the combination of nonlocality and
      vectorial coupling has a remarkable stabilizing action on multihumped solitons.
      In particular, we find that stable bound states featuring several field
      oscillations in each soliton component do exist. This affords stabilization of
      vector soliton trains incorporating a large number of humps, a class of
      structures known to self-destroy via strong instabilities in scalar settings.

PMID- 16802991
TI  - Simulation of a microfluidic flow-focusing device.
AB  - We present a model of microfluidic flow of several completely immiscible fluids
      and use it to simulate a whole flow focusing device chamber. Our efficient,
      practical model supports a large parameter space, spanned by surface wetting,
      surface tension, liquid-liquid wetting, viscosity ratio, and inlet velocity. It
      is based upon an N-component lattice Boltzmann method with interrupted
      coalescence [Dupin, Philos. Trans. R. Soc. London, Ser. A 362, 1885 (2004)], here
      adapted for calculations at low capillary and Reynolds numbers, with wetting and
      significantly reduced spurious flow. Results over 2 orders of magnitude in
      Reynolds number are presented.

PMID- 16802992
TI  - k-core (bootstrap) percolation on complex networks: critical phenomena and
      nonlocal effects.
AB  - We develop the theory of the -core (bootstrap) percolation on uncorrelated random
      networks with arbitrary degree distributions. We show that the -core percolation
      is an unusual, hybrid phase transition with a jump emergence of the k-core as at
      a first order phase transition but also with a critical singularity as at a
      continuous transition. We describe the properties of the -core, explain the
      meaning of the order parameter for the k-core percolation, and reveal the origin
      of the specific critical phenomena. We demonstrate that a so-called "corona" of
      the k-core plays a crucial role (corona is a subset of vertices in the k-core
      which have exactly neighbors in the -core). It turns out that the k-core
      percolation threshold is at the same time the percolation threshold of finite
      corona clusters. The mean separation of vertices in corona clusters plays the
      role of the correlation length and diverges at the critical point. We show that a
      random removal of even one vertex from the k-core may result in the collapse of a
      vast region of the k-core around the removed vertex. The mean size of this region
      diverges at the critical point. We find an exact mapping of the k-core
      percolation to a model of cooperative relaxation. This model undergoes critical
      relaxation with a divergent rate at some critical moment.

PMID- 16802993
TI  - Condensation phase transitions of symmetric conserved-mass aggregation model on
      complex networks.
AB  - We investigate condensation phase transitions of the symmetric conserved-mass
      aggregation (SCA) model on random networks (RNs) and scale-free networks (SFNs)
      with degree distribution P(k) approximately k(-gamma). In the SCA model, masses
      diffuse with unit rate, and unit mass chips off from mass with rate omega. The
      dynamics conserves total mass density rho. In the steady state, on RNs and SFNs
      with gamma > 3 for omega is not equal to infinity, we numerically show that the
      SCA model undergoes the same type of condensation transitions as those on regular
      lattices. However, the critical line rho(c)(omega) depends on network structures.
      On SFNs with gamma < or = 3, the fluid phase of exponential mass distribution
      completely disappears and no phase transitions occurs. Instead, the condensation
      with exponentially decaying background mass distribution always takes place for
      any nonzero density. For the existence of the condensed phase for gamma < or = 3
      at the zero density limit, we investigate one lamb-lion problem on RNs and SFNs.
      We numerically show that a lamb survives indefinitely with finite survival
      probability on RNs and SFNs with gamma > 3, and dies out exponentially on SFNs
      with gamma< or = 3. The finite lifetime of a lamb on SFNs with gamma < or = 3
      ensures the existence of the condensation at the zero density limit on SFNs with
      gamma < or = 3, at which direct numerical simulations are practically impossible.
      At omega = infinity, we numerically confirm that complete condensation takes
      place for any rho > 0 on RNs. Together with the recent study on SFNs, the
      complete condensation always occurs on both RNs and SFNs in zero range process
      with constant hopping rate.

PMID- 16802994
TI  - Universal asymptotic statistics of maximal relative height in one-dimensional
      solid-on-solid models.
AB  - We study the probability density function P(h(m), L) of the maximum relative
      height h(m) in a wide class of one-dimensional solid-on-solid models of finite
      size L. For all these lattice models, in the large-L limit, a central limit
      argument shows that, for periodic boundary conditions, P(h(m), L) takes a
      universal scaling form P(h(m), L) approximately radical(12w(L))(-1)
      f(h(m)radical(12w(L))(-1), with w(L) the width of the fluctuating interface f(x)
      and the Airy distribution function. For one instance of these models,
      corresponding to the extremely anisotropic Ising model in two dimensions, this
      result is obtained by an exact computation using the transfer matrix technique,
      valid for any L > 0. These arguments and exact analytical calculations are
      supported by numerical simulations, which show in addition that the subleading
      scaling function is also universal, up to a nonuniversal amplitude, and simply
      given by the derivative of the Airy distribution function f'(x).

PMID- 16802995
TI  - Universal mean moment rate profiles of earthquake ruptures.
AB  - Earthquake phenomenology exhibits a number of power law distributions including
      the Gutenberg-Richter frequency-size statistics and the Omori law for aftershock
      decay rates. In search for a basic model that renders correct predictions on long
      spatiotemporal scales, we discuss results associated with a heterogeneous fault
      with long-range stress-transfer interactions. To better understand earthquake
      dynamics we focus on faults with Gutenberg-Richter-like earthquake statistics and
      develop two universal scaling functions as a stronger test of the theory against
      observations than mere scaling exponents that have large error bars. Universal
      shape profiles contain crucial information on the underlying dynamics in a
      variety of systems. As in magnetic systems, we find that our analysis for
      earthquakes provides a good overall agreement between theory and observations,
      but with a potential discrepancy in one particular universal scaling function for
      moment rates. We primarily use mean field theory for the theoretical analysis,
      since it has been shown to be in the same universality class as the full three
      dimensional version of the model (up to logarithmic corrections). The results
      point to the existence of deep connections between the physics of avalanches in
      different systems.

PMID- 16802996
TI  - Scaling and universality in the counterion-condensation transition at charged
      cylinders.
AB  - Counterions at charged rodlike polymers exhibit a condensation transition at a
      critical temperature (or, equivalently, at a critical linear charge density for
      polymers), which dramatically influences various static and dynamic properties of
      charged polymer solutions. We address the critical and universal aspects of this
      transition for counterions at a single charged cylinder in two and three spatial
      dimensions using numerical and analytical methods. By introducing a Monte Carlo
      sampling method in logarithmic radial scale, we are able to numerically simulate
      the critical limit of infinite system size (corresponding to the infinite
      dilution limit) within tractable equilibration times. The critical exponents are
      determined for the inverse moments of the counterionic density profile (which
      play the role of the order parameters and represent the mean inverse localization
      length of counterions) both within mean-field theory and within Monte Carlo
      simulations. In three dimensions (3D), we demonstrate that correlation effects
      (neglected within mean-field theory) lead to an excessive accumulation of
      counterions near the charged cylinder below the critical temperature (i.e., in
      the condensation phase), while surprisingly, the critical region exhibits
      universal critical exponents in accordance with mean-field theory. Also in
      contrast with the typical trend in bulk critical phenomena, where fluctuations
      become more enhanced in lower dimensions, we demonstrate, using both numerical
      and analytical approaches, that mean-field theory becomes exact for the two
      dimensional (2D) counterion-cylinder system at all temperatures (Manning
      parameters), when the number of counterions tends to infinity. For a finite
      number of particles, however, the 2D problem displays a series of peculiar
      singular points (with diverging heat capacity), which reflect successive
      delocalization events of individual counterions from the central cylinder. In
      both 2D and 3D, the heat capacity shows a universal jump at the critical point
      and the internal energy develops a pronounced peak. The asymptotic behavior of
      the energy peak location is used to determine the critical temperature, which is
      also found to be in agreement with the mean-field prediction.

PMID- 16802997
TI  - Statistics of low energy excitations for the directed polymer in a random medium.
AB  - We consider a directed polymer of length L in a random medium of space dimension
      d = 1,2,3. The statistics of low energy excitations as a function of their size l
      is numerically evaluated. These excitations can be divided into bulk and boundary
      excitations, with respective densities rho(bulk)(L) (E = 0,l) and
      rho(boundary)(L)(E=0,l). We find that both densities follow the scaling behavior
      rho(bulk, boundary)(L)(E = 0,l)=L(-1-theta)(d)R(bulk,boundary)(x = l/L), where
      theta(d) is the exponent governing the energy fluctuations at zero temperature
      (with the well-known exact value theta(1)= 1/3 in one dimension). In the limit x
      = l/L --> 0, both scaling functions R(bulk)(x) and R(boundary)(x) behave as
      R(bulk,boundary)(x) approximately x(-1-theta)(d), leading to the droplet power
      law rho(bulk, boundary)(L) (E = 0,l) approximately l(-1-theta)(d) in the regime 1
      << l << L. Beyond their common singularity near x --> 0, the two scaling
      functions R(bulk,boundary)(x) are very different: whereas R(bulk)(x) decays
      monotonically for 0 < x < 1, the function R(boundary)(x) first decays for 0 < x <
      x(min), then grows for x(min) < x < 1, and finally presents a power law
      singularity R(boundary)(x) approximately (1-x)(-sigma)(d) near x -->1. The
      density of excitations of length l = L accordingly decays as rho(boundary)(L)(E =
      0,l = L) approximately L(-lambda)(d) where gamma(d) = 1+ theta(d) - lambda(d). We
      obtain lambda(1) approximately 10.67, lambda(2) = 0.53, and lambda(3)
      approximately 0.39, suggesting the possible relation lambda(d) = 2theta(d).

PMID- 16802998
TI  - Rotating states of self-propelling particles in two dimensions.
AB  - We present particle-based simulations and a continuum theory for steady rotating
      flocks formed by self-propelling particles (SPPs) in two-dimensional space. Our
      models include realistic but simple rules for the self-propelling, drag, and
      interparticle interactions. Among other coherent structures, in particle-based
      simulations we find steady rotating flocks when the velocity of the particles
      lacks long-range alignment. Physical characteristics of the rotating flock are
      measured and discussed. We construct a phenomenological continuum model and seek
      steady-state solutions for a rotating flock. We show that the velocity and
      density profiles become simple in two limits. In the limit of weak alignment, we
      find that all particles move with the same speed and the density of particles
      vanishes near the center of the flock due to the divergence of centripetal force.
      In the limit of strong body force, the density of particles within the flock is
      uniform and the velocity of the particles close to the center of the flock
      becomes small.

PMID- 16802999
TI  - Hybrid graphs as a framework for the small-world effect.
AB  - In this paper we formalize the small-world effect which describes the surprising
      fact that a hybrid graph composed of a local graph component and a very sparse
      random graph has a diameter of O(ln n) whereby the diameter of both components
      alone is much higher. We show that a large family of these hybrid graphs shows
      this effect and that this generalized family also includes classic small-world
      models proposed by various authors although not all of them are captured by the
      small-world definition given by Watts and Strogatz. Furthermore, we give a
      detailed upper bound of the hybrid's graph diameter for different choices of the
      expected number of random edges by applying a new kind of proof pattern that is
      applicable to a large number of hybrid graphs. The focus in this paper is on
      presenting a flexible family of hybrid graphs showing the small-world effect that
      can be tuned closely to real-world systems.

PMID- 16803000
TI  - Generalized local-world models for weighted networks.
AB  - Based on the weighted scale-free network model proposed by Barrat, Barthelemy,
      and Vespignani [Phys. Rev. Lett. 92, 228701 (2004)] and enlightened by our local
      world concept [Li and Chen, Physica A 328, 274 (2003)], we propose two
      generalized local-world (GLW) models for weighted complex networks. Theoretical
      analysis and numerical simulations show that the GLW models generate weighted
      networks as a crossover between exponential and scale-free weighted networks, and
      exhibit an alteration from assortative networks to disassortative networks.

PMID- 16803001
TI  - Universality and quantum effects in one-component critical fluids.
AB  - Nonuniversal scale transformations of the physical fields are extended to pure
      quantum fluids and used to calculate the susceptibility, the specific heat, and
      the order parameter density along the critical isochore of near its liquid-vapor
      critical point. Within the so-called preasymptotic domain, where the Wegner
      expansion restricted to the first term of confluent corrections to scaling is
      expected to be valid, the results are in agreement with the experimental
      measurements and recent predictions, either based on the minimal-substraction
      renormalization and the massive renormalization schemes within phi (4)(d = 3) (n
      = 1)the model, or based on the crossover parametric equation of state for Ising
      like systems.

PMID- 16803002
TI  - Two-dimensional small-world networks: navigation with local information.
AB  - A navigation process is studied on a variant of the Watts-Strogatz small-world
      network model embedded on a square lattice. With probability , each vertex sends
      out a long-range link, and the probability of the other end of this link falling
      on a vertex at lattice distance away decays as r(-a). Vertices on the network
      have knowledge of only their nearest neighbors. In a navigation process, messages
      are forwarded to a designated target. For alpha < 3 and alpha not equal to 2, a
      scaling relation is found between the average actual path length and , where is
      the average length of the additional long range links. Given pL > 1, a dynamic
      small world effect is observed, and the behavior of the scaling function at large
      enough is obtained. At alpha = 2 and 3, this kind of scaling breaks down, and
      different functions of the average actual path length are obtained. For alpha >
      3, the average actual path length is nearly linear with network size.

PMID- 16803003
TI  - Maximum independent set on diluted triangular lattices.
AB  - Core percolation and maximum independent set on random graphs have recently been
      characterized using the methods of statistical physics. Here we present a
      statistical physics study of these problems on bond diluted triangular lattices.
      Core percolation critical behavior is found to be consistent with the standard
      percolation values, though there are strong finite size effects. A transfer
      matrix method is developed and applied to find accurate values of the density and
      degeneracy of the maximum independent set on lattices of limited width but large
      length. An extrapolation of these results to the infinite lattice limit yields
      high precision results, which are tabulated. These results are compared to
      results found using both vertex based and edge based local probability recursion
      algorithms, which have proven useful in the analysis of hard computational
      problems, such as the satisfiability problem.

PMID- 16803004
TI  - Hydrogen bond topology and the ice VII/VIII and Ih/XI proton ordering phase
      transitions.
AB  - Ice Ih, ordinary ice at atmospheric pressure, is a proton-disordered crystal that
      when cooled under special conditions is believed to transform to ferroelectric
      proton-ordered ice XI, but this transformation is still subject to controversy.
      Ice VII, also proton disordered throughout its region of stability, transforms to
      proton-ordered ice VIII upon cooling. In contrast to the ice Ih/XI transition,
      the VII/VIII transition and the crystal structure of ice VIII are well
      characterized. In order to shed some light on the ice Ih proton ordering
      transition, we present the results of periodic electronic density functional
      theory calculations and statistical simulations. We are able to describe the
      small energy differences among the innumerable H-bond configurations possible in
      a large simulation cell by using an analytic theory to extrapolate from
      electronic DFT calculations on small unit cells to cells large enough to
      approximate the thermodynamic limit. We first validate our methods by comparing
      our predictions to the well-characterized ice VII/VIII proton ordering
      transition, finding agreement with respect to both the transition temperature and
      structure of the low-temperature phase. For ice Ih, our results indicate that a
      proton-ordered phase is attainable at low temperatures, the structure of which is
      in agreement with the experimentally proposed ferroelectric structure. The
      predicted transition temperature of is in qualitative agreement with the observed
      transition at on KOH-doped ice samples.

PMID- 16803005
TI  - Universal features and tail analysis of the order-parameter distribution of the
      two-dimensional Ising model: an entropic sampling Monte Carlo study.
AB  - We present a numerical study of the order-parameter probability density function
      (PDF) of the square Ising model for lattices with linear sizes L = 80 - 140. A
      recent efficient entropic sampling scheme, combining the Wang-Landau and broad
      histogram methods and based on the high levels of the Wang-Landau process in
      dominant energy subspaces is employed. We find that for large lattices there
      exists a stable window of the scaled order-parameter in which the full ansatz
      including the pre-exponential factor for the tail regime of the universal PDF is
      well obeyed. This window is used to estimate the equation of state exponent and
      to observe the behavior of the universal constants implicit in the functional
      form of the universal PDF. The probability densities are used to estimate the
      universal Privman-Fisher coefficient and to investigate whether one could obtain
      reliable estimates of the universal constants controlling the asymptotic behavior
      of the tail regime.

PMID- 16803006
TI  - Effects of preference for attachment to low-degree nodes on the degree
      distributions of a growing directed network and a simple food-web model.
AB  - We study the growth of a directed network, in which the growth is constrained by
      the cost of adding links to the existing nodes. We propose a preferential
      attachment scheme, in which a new node attaches to an existing node i with
      probability II(k(i)) approximately k(-1), where k(i) is the number of outgoing
      links at i. We calculate the degree distribution for the outgoing links in the
      asymptotic regime t --> infinity, n(k) both analytically and by Monte Carlo
      simulations. The distribution decays like kmu(k)/Tau(k) for large k, where is a
      constant. We investigate the effect of this preferential-attachment scheme, by
      comparing the results to an equivalent growth model with a degree-independent
      probability of attachment, which gives an exponential outdegree distribution.
      Also, we relate this mechanism to simple food-web models by implementing it in
      the cascade model. We show that the low-degree preferential-attachment mechanism
      breaks the symmetry between in- and outdegree distributions in the cascade model.
      It also causes a faster decay in the tails of the outdegree distributions for
      both our network growth model and the cascade model.

PMID- 16803007
TI  - Bulk and surface phase transitions in the three-dimensional O4 spin model.
AB  - We investigate the O(4) spin model on the simple-cubic lattice by means of the
      Wolff cluster algorithm. Using the toroidal boundary condition, we locate the
      bulk critical point at coupling K(c) = 0.935 856(2), and determine the bulk
      thermal magnetic renormalization exponents as y(t) = 1.337 5(15) and y(h) = 2.482
      0(2), respectively. The universal ratio Q=m(2)(2)/m(4) is also determined as
      0.9142(1). The precision of these estimates significantly improves over that of
      the existing results. Then, we simulate the critical O(4) model with two open
      surfaces on which the coupling strength K(1) can be varied. At the ordinary
      transitions, the surface magnetic exponent is determined as y((o))(h1) = 1.020
      2(12). Further, we find a so-called special surface transition at (k) = K(1)/K-1
      = 1.258(20). At this point, the surface thermal exponent y(s)(t1) is rather close
      to zero, and we cannot exclude that the corresponding surface transition is
      Kosterlitz-Thouless-like. The surface magnetic exponent is y((s))/h1 = 1.816(2).

PMID- 16803008
TI  - Fluctuation-dissipation theorem and the linear Glauber model.
AB  - We obtain exact expressions for the two-time autocorrelation and response
      functions of the -dimensional linear Glauber model. Although this linear model
      does not obey detailed balance in dimensions d > or = 2, we show that the usual
      form of the fluctuation-dissipation ratio still holds in the stationary regime.
      In the transient regime, we show the occurrence of aging, with a special limit of
      the fluctuation-dissipation ratio, x(infinity) = 1/2, for a quench at the
      critical point.

PMID- 16803009
TI  - Critical behavior of a colloid-polymer mixture confined between walls.
AB  - We investigate the influence of confinement on phase separation in colloid
      polymer mixtures. To describe the particle interactions, the colloid-polymer
      model of Asakura and Oosawa [J. Chem. Phys. 22, 1255 (1954)] is used. Grand
      canonical Monte Carlo simulations are then applied to this model confined between
      two parallel hard walls, separated by a distance D = 5 colloid diameters. We
      focus on the critical regime of the phase separation and look for signs of
      crossover from three-dimensional (3D) Ising to two-dimensional (2D) Ising
      universality. To extract the critical behavior, finite size scaling techniques
      are used, including the recently proposed algorithm of Kim et al [Phys. Rev.
      Lett. 91, 065701 (2003)]. Our results point to "effective" critical exponents
      that differ profoundly from 3D Ising values, and that are already very close to
      2D Ising values. In particular, we observe that the critical exponent of the
      order parameter in the confined system is smaller than in 3D bulk, yielding a
      "flatter" binodal. Our results also show an increase in the critical colloid
      packing fraction in the confined system with respect to the bulk. The latter
      seems consistent with theoretical expectations, although subtleties due to
      singularities in the critical behavior of the coexistence diameter cannot be
      ruled out.

PMID- 16803010
TI  - Superstatistical random-matrix-theory approach to transition intensities in mixed
      systems.
AB  - We study the fluctuation properties of transition intensities applying a recently
      proposed generalization of the random matrix theory, which is based on Beck and
      Cohen's superstatistics. We obtain an analytic expression for the distribution of
      the reduced transition probabilities that applies to systems undergoing a
      transition out of chaos. The obtained distribution fits the results of a previous
      nuclear shell model calculations for some electromagnetic transitions that
      deviate from the Porter-Thomas distribution. It agrees with the experimental
      reduced transition probabilities for the nucleus better than the commonly used
      chi(2) distribution.

PMID- 16803011
TI  - Fracture spacing in layered materials and pattern transition from parallel to
      polygonal fractures.
AB  - We perform three-dimensional simulations of fracture growth in a three-layered
      plate model with an embedded heterogeneous layer under horizontal biaxial stretch
      (representing stretch from directional to isotropic) by the finite element
      approach. The fractures develop under a quasistatical, slowly increasing biaxial
      strain. The material inhomogeneities are accounted for by assigning each element
      a failure threshold that is defined by a given statistical distribution. A
      universal scale law of fracture spacing to biaxial strain in terms of principal
      stress ratio is well demonstrated in a three-dimensional fashion. The numerically
      obtained fracture patterns show a continuous pattern transition from parallel
      fractures, laddering fracture to polygonal fractures, which depends strongly on
      the far-field loading conditions in terms of principal stress ratio lambda =
      sigma(2)/sigma(1), from uniaxial (lambda = 0), anisotropic (0 < lambda < 1) to
      isotropic stretch (lambda = 1). We find that, except for further opening of
      existing fractures after they are well-developed (saturation), new fractures may
      also initiate and propagate along the interface between layers, which may serve
      as another mechanism to accommodate additional strain for fracture saturated
      layers.

PMID- 16803012
TI  - Generation of long-range correlations in large systems as an optimization
      problem.
AB  - We propose an efficient method of generating long-range correlations in large
      systems. The development of this method was motivated by the problem of
      constructing an optimal model for a large-scale porous medium. There are
      typically long-range correlations in the properties of such porous media, such as
      their permeability and porosity, for which there are usually only limited data.
      The optimal model must not only honor (preserve) the available data and their
      correlation function, but also accurately predict the future behavior of fluid
      flow in the media. We formulate the problem of generating the long-range
      correlations as one of optimization, and utilize simulated annealing to generate
      a d-dimensional array which contains the correlations and honors the existing
      data. The optimization process is based on the data's correlation function. The
      method is, therefore, free of the many numerical difficulties and/or limitations
      that most previous techniques suffer from. It is completely general and may be
      used for generating long-range correlations with any type of correlation
      function, in both isotropic and anisotropic media. Representative examples are
      presented, and the method's efficiency and accuracy are discussed.

PMID- 16803013
TI  - Degree-dependent intervertex separation in complex networks.
AB  - We study the mean length (l)(k) of the shortest paths between a vertex of degree
      k and other vertices in growing networks, where correlations are essential. In a
      number of deterministic scale-free networks we observe a power-law correction to
      a logarithmic dependence, (l)(k) = A ln[N/k((gamma-1)/2)]-Ck(gamma-1)/N+ in a
      wide range of network sizes. Here N is the number of vertices in the network,
      gamma is the degree distribution exponent, and the coefficients A and C depend on
      a network. We compare this law with a corresponding (l)(k) dependence obtained
      for random scale-free networks growing through the preferential attachment
      mechanism. In stochastic and deterministic growing trees with an exponential
      degree distribution, we observe a linear dependence on degree,
      (l)(k)approximately A ln N-Ck. We compare our findings for growing networks with
      those for uncorrelated graphs.

PMID- 16803014
TI  - Noise-induced spatiotemporal patterns in a bistable reaction-diffusion system:
      photoelectron emission microscopy experiments and modeling of the oxidation
      reaction on Ir(111).
AB  - We use photoelectron emission microscopy (PEEM) measurements to study the
      spatiotemporal patterns obtained for the CO oxidation reaction on Ir(111) as a
      function of the noise strength we superpose on the CO and the oxygen fractions of
      the constant total reactant gas flux. The investigations are focused on the
      bistable regime this reaction displays including its monostable vicinity.
      Simultaneously we analyze numerically the underlying reaction-diffusion (RD)
      equations in two spatial dimensions. For intrinsic and/or small strength of the
      external noise we find transitions from the locally stable to the globally stable
      branch via slow nucleation and growth of islands of the globally stable state:
      oxygen or CO, respectively. With increasing noise strength the number of islands
      as well as their growth rate increases. These phenomena are very well reproduced
      by numerical calculations of the RD model. For sufficiently large noise strength
      we observe bursts from CO rich to oxygen rich and back as well as switching
      between the two states. While such phenomena are also obtained from the model
      calculations, their experimentally observed spatial scales were not
      satisfactorily reproduced using the same approach as for the lower noise
      strengths.

PMID- 16803015
TI  - From scale-free to Erdos-Renyi networks.
AB  - We analyze a model that interpolates between scale-free and Erdos-Renyi networks.
      The model introduced generates a one-parameter family of networks and allows one
      to analyze the role of structural heterogeneity. Analytical calculations are
      compared with extensive numerical simulations in order to describe the transition
      between these two important classes of networks. Finally, an application of the
      proposed model to the study of the percolation transition is presented.

PMID- 16803016
TI  - Dissipative sandpile models with universal exponents.
AB  - We consider a dissipative variant of the stochastic-Abelian sandpile model on a
      two-dimensional lattice. The boundaries are closed and the dissipation is due to
      the fact that each toppled grain is removed from the lattice with probability
      epsilon. It is shown that the scaling properties of this model are in the
      universality class of the stochastic-Abelian models with conservative dynamics
      and open boundaries. In particular, the dissipation rate epsilon can be adjusted
      according to a suitable function epsilon = f(L), such that the avalanche size
      distribution will coincide with that of the conservative model on a finite
      lattice of size L.

PMID- 16803018
TI  - Sleep dynamics: a self-organized critical system.
AB  - In psychiatric and neurological diseases, sleep is often perturbed. Moreover,
      recent works on humans and animals tend to show that sleep plays a strong role in
      memory processes. Reciprocally, sleep dynamics following a learning task is
      modified [Hubert, Nature (London) 02663, 1 (2004), Peigneux, Neuron 44, 535
      (2004)]. However, sleep analysis in humans and animals is often limited to the
      total sleep and wake duration quantification. These two parameters are not fully
      able to characterize the sleep dynamics. In mammals sleep presents a complex
      organization with an alternation of slow wave sleep (SWS) and paradoxical sleep
      (PS) episodes. Moreover, it has been shown recently that these sleep episodes are
      frequently interrupted by micro-arousal (without awakening). We present here a
      detailed analysis of the basal sleep properties emerging from the mechanisms
      underlying the vigilance states alternation in an animal model. These properties
      present a self-organized critical system signature and reveal the existence of
      two W, two SWS, and a PS structure exhibiting a criticality as met in sand piles.
      We propose a theoretical model of the sleep dynamics based on several interacting
      neuronal populations. This new model of sleep dynamics presents the same
      properties as experimentally observed, and explains the variability of the
      collected data. This experimental and theoretical study suggests that sleep
      dynamics shares several common features with critical systems.

PMID- 16803017
TI  - Phenomenological theory giving the full statistics of the position of fluctuating
      pulled fronts.
AB  - We propose a phenomenological description for the effect of a weak noise on the
      position of a front described by the Fisher-Kolmogorov-Petrovsky-Piscounov
      equation or any other traveling-wave equation in the same class. Our scenario is
      based on four hypotheses on the relevant mechanism for the diffusion of the
      front. Our parameter-free analytical predictions for the velocity of the front,
      its diffusion constant and higher cumulants of its position agree with numerical
      simulations.

PMID- 16803019
TI  - Dynamics of opinion formation in a small-world network.
AB  - The dynamical process of opinion formation within a model using a local majority
      opinion updating rule is studied numerically in networks with the small-world
      geometrical property. The network is one in which shortcuts are added to randomly
      chosen pairs of nodes in an underlying regular lattice. The presence of a small
      number of shortcuts is found to shorten the time to reach a consensus
      significantly. The effects of having shortcuts in a lattice of fixed spatial
      dimension are shown to be analogous to that of increasing the spatial dimension
      in regular lattices. The shortening of the consensus time is shown to be related
      to the shortening of the mean shortest path as shortcuts are added. Results can
      also be translated into that of the dynamics of a spin system in a small-world
      network.

PMID- 16803021
TI  - Winding number locking on a two-dimensional torus: synchronization of
      quasiperiodic motions.
AB  - We propose a new autonomous dynamical system of dimension N = 4 that demonstrates
      the regime of stable two-frequency motions and period-doubling bifurcations of a
      two-dimensional torus. It is shown that the period-doubling bifurcation of the
      two-dimensional torus is not followed by the resonance phenomenon, and the two
      dimensional ergodic torus undergoes a period-doubling bifurcation. The
      interaction of two generators is also analyzed. The phenomenon of external and
      mutual synchronization of two-frequency oscillations is observed, for which
      winding number locking on a two-dimensional torus takes place.

PMID- 16803020
TI  - Nontwist non-Hamiltonian systems.
AB  - We show that the nontwist phenomena previously observed in Hamiltonian systems
      exist also in time-reversible non-Hamiltonian systems. In particular, we study
      the two standard collision-reconnection scenarios and we compute the parameter
      space breakup diagram of the shearless torus. Besides the Hamiltonian routes, the
      breakup may occur due to the onset of attractors. We study these phenomena in
      coupled phase oscillators and in non-area-preserving maps.

PMID- 16803022
TI  - Quantum resonance and antiresonance for a periodically kicked Bose-Einstein
      condensate in a one-dimensional box.
AB  - We investigate the quantum dynamics of a periodically kicked Bose-Einstein
      condensate (BEC) confined in a one-dimensional (1D) box both numerically and
      theoretically, emphasizing on the phenomena of quantum resonance and
      antiresonance. The quantum resonant behavior of BEC is different from the single
      particle case but the antiresonance condition (Tau = 2pi and alpha = 0) is not
      affected by the atomic interaction. For the antiresonance case, the nonlinearity
      (atom interaction) causes the transition between oscillation and quantum beating.
      For the quantum resonance case, because of the coherence of BEC, the energy
      increase is oscillating and the rate is dramatically affected by the many-body
      interaction. We also discuss the relation between the quantum resonant behavior
      and the Kolmogorov-Arnold-Moser (KAM) or non-KAM property of the corresponding
      classical system.

PMID- 16803023
TI  - Analyzing memory effects of complex systems from time series.
AB  - A numerical algorithm is presented in order to determine all coefficients of the
      Mori-Zwanzig equation from a given finite time series. The algorithm is
      applicable to observables of arbitrary complex systems. Meteorological and
      financial systems are investigated. By analyzing directional variables and
      amplitudes we are able to observe and discuss memory effects on different time
      scales. We show that analyzing the memory kernel provides important insights into
      the dynamics of a complex system.

PMID- 16803024
TI  - Stochastic phase dynamics: multiscale behavior and coherence measures.
AB  - A multiscale approach is used to derive stochastic amplitude and phase dynamics
      for a canonical noise-sensitive model exhibiting coherence resonance. Explicit
      expressions for the dependence on noise levels and model type are compared with
      computational coherence measures.

PMID- 16803025
TI  - Stability of simple periodic orbits and chaos in a Fermi-Pasta-Ulam lattice.
AB  - We investigate the connection between local and global dynamics in the Fermi
      Pasta-Ulam (FPU) beta model from the point of view of stability of its simplest
      periodic orbits (SPO's). In particular, we show that there is a relatively high-q
      mode [q = 2(N + 1)/3] of the linear lattice, having one particle fixed every two
      oppositely moving ones (called SPO2 here), which can be exactly continued to the
      nonlinear case for N = 5 + 3m, m = 0,1,2,, and whose first destabilization E(2u),
      as the energy (or beta) increases for any fixed N, practically coincides with the
      onset of a "weak" form of chaos preceding the breakdown of FPU recurrences, as
      predicted recently in a similar study of the continuation of a very low (q = 3)
      mode of the corresponding linear chain. This energy threshold per particle
      behaves like E(2u)/N alpha N(-2). We also follow exactly the properties of
      another SPO [with q = (N + 1)/2] in which fixed and moving particles are
      interchanged (called SPO1 here) and which destabilizes at higher energies than
      SPO2, since E(1u)/N alpha N(-1). We find that, immediately after their first
      destabilization, these SPO's have different (positive) Lyapunov spectra in their
      vicinity. However, as the energy increases further (at fixed N), these spectra
      converge to the same exponentially decreasing function, thus providing strong
      evidence that the chaotic regions around SPO1 and SPO2 have "merged" and large
      scale chaos has spread throughout the lattice. Since these results hold for N
      arbitrarily large, they suggest a direct approach by which one can use local
      stability analysis of SPO's to estimate the energy threshold at which a
      transition to ergodicity occurs and thermodynamic properties such as Kolmogorov
      Sinai entropies per particle can be computed for similar one-dimensional
      lattices.

PMID- 16803026
TI  - Spatial recurrence plots.
AB  - We propose an extension of the recurrence plot concept to perform quantitative
      analyzes of roughness and disorder of spatial patterns at a fixed time. We
      introduce spatial recurrence plots (SRPs) as a graphical representation of the
      pointwise correlation matrix, in terms of a two-dimensional spatial return plot.
      This technique is applied to the study of complex patterns generated by coupled
      map lattices, which are characterized by measures of complexity based on SRPs. We
      show that the complexity measures we propose for SRPs provide a systematic way of
      investigating the distribution of spatially coherent structures, such as
      synchronization domains, in lattice profiles. This approach has potential for
      many more applications, e.g., in surface roughness analyzes.

PMID- 16803027
TI  - Periodic spatiotemporal patterns in a two-dimensional two-variable reaction
      diffusion model.
AB  - Periodic spatiotemporal two-dimensional (2D) asymptotic patterns in an excitable
      two-variable thermochemical (reaction-diffusion) system are shown. In a one
      dimensional system the traveling impulse which reflects from impermeable
      boundaries is a stable asymptotic solution if the diffusion coefficient of the
      reactant is greater than the thermal diffusivity of the system. Periodic patterns
      of two symmetries are presented in the 2D system: the impulse of excitation
      propagating along the diagonal of a square spatial domain and a structure
      consisting of curved impulses which propagate in the direction perpendicular to
      one side of a rectangular domain.

PMID- 16803028
TI  - Regular patterns in dichotomically driven activator-inhibitor dynamics.
AB  - We investigate Turing pattern formation in the presence of additive dichotomous
      fluctuations in the context of an extended system with diffusive coupling and
      FitzHugh-Nagumo kinetics. The fluctuations vary in space and/or time. Depending
      on the realization of the dichotomous switching the system is, at a given time
      (for spatial disorder at a given position) in one of two possible excitable
      dynamical regimes. Each of the two excitable dynamics for itself does not support
      pattern formation. With proper dichotomous fluctuations, however, the homogeneous
      steady state is destabilized via a Turing instability. We investigate the
      influence of different switching rates (different correlation length of the
      spatial disorder) on pattern formation. We find three distinct mechanisms: For
      slow switching existing boundaries become unstable, for high rates the system
      exhibits "effective bistability" which allows for a Turing instability. For
      medium rates the fluctuations create spatial structures via a new mechanism where
      the influence of the fluctuations is twofold. First they produce local
      inhomogeneities, which then grow (again caused by fluctuations) until the whole
      space is covered. Utilizing a nonlinear map approach we show bistability of a
      period-one and a period-two orbit being associated with the steady homogeneous
      and the Turing pattern state, respectively. Finally, for purely static
      dichotomous disorder we find destabilization of homogeneous steady states for
      finite nonzero correlation length of the disorder resulting again in Turing
      patterns.

PMID- 16803029
TI  - Conserved quantities and adaptation to the edge of chaos.
AB  - Certain dynamical systems, such as the shift map and the logistic map, have an
      edge of chaos in their parameter spaces. On one side of this edge, the dynamics
      are chaotic for many parameter values, on the other side of the edge they are
      periodic. We find that discrete-time dynamical systems with wavelet filtered
      feedback from the dynamical variable to the parameters are attracted to a narrow
      parameter range near the edge of chaos, the periodic boundary regime. We show
      that the migration from the chaotic regime to the periodic boundary regime can be
      attributed to a conserved quantity, and find that such adaptation to the edge of
      chaos is accompanied by a depopulation of the chaotic regime. We use this
      conserved quantity to determine the location of the periodic boundary regime and
      show that its size is proportional to the size of the feedback. Further, we
      compute the dynamics of the probability density for the parameter for a specific
      example.

PMID- 16803030
TI  - Localized states in the generalized Swift-Hohenberg equation.
AB  - The Swift-Hohenberg equation with quadratic and cubic nonlinearities exhibits a
      remarkable wealth of stable spatially localized states. The presence of these
      states is related to a phenomenon called homoclinic snaking. Numerical
      computations are used to illustrate the changes in the localized solution as it
      grows in spatial extent and to determine the stability properties of the
      resulting states. The evolution of the localized states once they lose stability
      is illustrated using direct simulations in time.

PMID- 16803031
TI  - Turbulent mixing with physical mass diffusion.
AB  - Simulated mixing rates of the Rayleigh-Taylor instability for miscible fluids
      with physical mass diffusion are shown to agree with experiment; for immiscible
      fluids with physical values of surface tension the numerical data lie in the
      center of the range of experimental values. The simulations are based on an
      improved front tracking algorithm to control numerical surface tension and on
      improved physical modeling to allow physical values of mass diffusion or surface
      tension. Compressibility, after correction for variable density effects, has also
      been shown to have a strong influence on mixing rates. In summary, we find
      significant dependence of the mixing rates on scale breaking phenomena. We
      introduce tools to analyze the bubble merger process and confirm that bubble
      interactions, as in a bubble merger model, drive the mixing growth rate.

PMID- 16803032
TI  - Theory of light emission in sonoluminescence as thermal radiation.
AB  - Based on the model proposed by Hilgenfeldt [Nature (London) 398, 401 (1999)], we
      present here a comprehensive theory of thermal radiation in single-bubble
      sonoluminescence (SBSL). We first invoke the generalized Kirchhoff's law to
      obtain the thermal emissivity from the absorption cross section of a multilayered
      sphere (MLS). A sonoluminescing bubble, whose internal structure is determined
      from hydrodynamic simulations, is then modeled as a MLS and in turn the thermal
      radiation is evaluated. Numerical results obtained from simulations for argon
      bubbles show that our theory successfully captures the major features observed in
      SBSL experiments.

PMID- 16803033
TI  - Controlling drift-wave turbulence using time-delay and space-shift
      autosynchronization feedback.
AB  - Drift-wave turbulence control in a one-dimensional nonlinear drift-wave equation
      driven by a sinusoidal wave is considered. We apply time-delay and space-shift
      feedback signals, to suppress turbulence. By using global and local pinning
      strategies, we show numerically that the turbulent state can be controlled to
      periodic states effectively if appropriate time-delay length and space-shift
      distance are chosen. The physical mechanism of the control scheme is understood
      based on the energy-minimum principle.

PMID- 16803034
TI  - Oscillating large-scale circulation in turbulent Rayleigh-Benard convection.
AB  - We report on the dynamics and structure of the turbulent velocity field in a high
      Rayleigh-number (Ra = 5.9 x 10(8))thermal convection cell with an aspect ratio of
      4. Spectral density functions (measured with laser Doppler velocimetry) indicated
      the existence of a large-scale periodic component. The long-time mean flow field
      (measured with particle image velocimetry) revealed that the large-scale
      circulation in the aspect-ratio-4 cell consists of two corotating rolls. The
      periodicity in the flow could be traced back to the alternating growth and decay
      of these rolls.

PMID- 16803035
TI  - Electro-osmotic flow and mixing in heterogeneous microchannels.
AB  - Analytical and numerical studies of secondary electro-osmotic flow (EOF) and its
      mixing in microchannels with heterogeneous zeta potentials are carried out in the
      present work. The secondary EOFs are analyzed by solving the Stokes equation with
      heterogeneous slip velocity boundary conditions. The analytical results obtained
      are compared with the direct numerical simulation of the Navier-Stokes equations.
      The secondary EOFs could transport scalar in larger areas and increase the scalar
      gradients, which significantly improve the mixing rate of scalars. It is shown
      that the heterogeneous zeta potentials could generate complex flow patterns and
      be used to enhance scalar mixing.

PMID- 16803036
TI  - Thin double layer approximation to describe streaming current fields in complex
      geometries: analytical framework and applications to microfluidics.
AB  - We set up an analytical framework that allows one to describe and compute
      streaming effects and electro-osmosis on an equal footing. This framework relies
      on the thin double layer approximation commonly used for description of
      electroosmotic flows, but rarely used for streaming problems. Using this
      framework we quantitatively assess the induction of bulk streaming current
      patterns by topographic or charge heterogeneities on surfaces. This too also
      permits analytical computation of all linear electrokinetic effects in complex
      microfluidic geometries, and we discuss a few immediate applications.

PMID- 16803037
TI  - Sporadic feedback control of flow turbulence.
AB  - In this work we consider the problem of flow turbulence control in a two
      dimensional Navier-Stokes equation. We suggest a control strategy which
      sporadically applies global feedback to a single velocity component of the
      velocity field. It is found that this control strategy can significantly enhance
      the control efficiency when the optimal fraction for the control period is
      suitably chosen, both larger and smaller control time fractions may reduce the
      control precision. The physical mechanism underlying this interesting and strange
      behavior is heuristically analyzed, based on mode-mode interactions.

PMID- 16803038
TI  - Inversion formula of multifractal energy dissipation in three-dimensional fully
      developed turbulence.
AB  - The concept of inverse statistics in turbulence has attracted much attention in
      recent years. It is argued that the scaling exponents of the direct structure
      functions and the inverse structure functions satisfy an inversion formula. This
      proposition has already been verified by numerical data using the shell model.
      However, no direct evidence was reported for experimental three-dimensional
      turbulence. We propose to test the inversion formula using experimental data of
      three-dimensional fully developed turbulence by considering the energy
      dissipation rates instead of the usual efforts on the structure functions. The
      moments of the exit distances are shown to exhibit nice multifractality. The
      inversion formula between the direct and inverse exponents is then verified.

PMID- 16803039
TI  - Dense bubble flow in a silo: an unusual flow of a dispersed medium.
AB  - The dense flow of air bubbles in a two-dimensional silo (through an aperture D)
      filled with a liquid is studied experimentally. A particle tracking technique has
      been used to bring out the main properties of the flow: displacements of the
      bubbles, transverse, and axial velocities. The behavior of the air bubbles is
      observed to present similarities with nondeformable solid grains in a granular
      flow. Nevertheless, a correlation between the bubble velocities and their
      deformations has been evidenced. Moreover, a new discharge law (Beverloo like)
      must be considered for such a system, where the flow rate is observed to vary as
      D(1/2) and depends on the deformability of the particles.

PMID- 16803040
TI  - Effect of compaction history on the fluidization behavior of fine cohesive
      powders.
AB  - Fine particles agglomerate in the fluidized state due to the strength of
      interparticle attractive forces as compared to particle weight. Interparticle
      adhesion can be largely increased by consolidation stresses applied during powder
      handling. As a consequence, fragments of the consolidated powder may persist when
      the powder is fluidized, which gives rise to large agglomerates of strongly
      adhered particles in fluidization. This history-dependent effect can be minimized
      by coating the particles with surface additives such as silica nanoparticles. In
      this paper, we investigate the effect of high consolidation stresses sigma(c)
      previously applied to samples of silica-coated fine particles on their
      fluidization behavior. Our experimental measurements show that, even though
      homogeneous fluidization is still observed, the average agglomerate size and
      fractal dimension of the agglomerates increase as sigma(c) is increased. Bed
      expansion in the fluidized state is hindered by previously applied high
      consolidations, which we attribute to an increase of the largest stable size of
      mesoscopic fluid pockets. As a consequence, we observe that the initiation of
      macroscopic bubbling is delayed up to larger values of the fluid velocity.

PMID- 16803041
TI  - Mean electromotive force due to turbulence of a conducting fluid in the presence
      of mean flow.
AB  - The mean electromotive force caused by turbulence of an electrically conducting
      fluid, which plays a central part in mean-field electrodynamics, is calculated
      for a rotating fluid. Going beyond most of the investigations on this topic, an
      additional mean motion in the rotating frame is taken into account. One
      motivation for our investigation originates from a planned laboratory experiment
      with a Ponomarenko-type dynamo. In view of this application the second-order
      correlation approximation is used. The investigation is of high interest in
      astrophysical context, too. Some contributions to the mean electromotive are
      revealed which have not been considered so far, in particular contributions to
      the effect and related effects due to the gradient of the mean velocity. Their
      relevance for dynamo processes is discussed. In a forthcoming paper the results
      reported here will be specified to the situation in the laboratory and partially
      compared with experimental findings.

PMID- 16803042
TI  - Azimuthal motion of the mean wind in turbulent thermal convection.
AB  - We present an experimental study of the azimuthal motion of the mean wind in
      turbulent thermal convection. The experiments were conducted with cylindrical
      convection cells of unity aspect ratio and over the range of the Rayleigh number
      from 1 x 10(9) to 1 x 10(10). The azimuthal angle of the circulation plane of the
      mean wind was measured using both the particle image velocimetry and flow
      visualization techniques. It is found that the azimuthal motion consists of
      erratic fluctuations and a time-periodic oscillation. The orientation of the wind
      is found to be "locked," i.e., it fluctuates about a preferred direction most of
      the time with all other orientations appearing as "transient states," and large
      excursions of the azimuthal angle often result in a net rotation which takes the
      wind back to the preferred orientation. The rate of erratic rotation of the
      circulation plane is found to have a strong dependence on Ra. Our result suggests
      that the oscillatory motion of the wind in its vertically oriented circulation
      plane and the orientational oscillation of the circulation plane itself have the
      same dynamic origin.

PMID- 16803043
TI  - ac electrokinetic micropumps: the effect of geometrical confinement, Faradaic
      current injection, and nonlinear surface capacitance.
AB  - Recent experiments have demonstrated that ac electrokinetic micropumps permit
      integrable, local, and fast pumping (velocities approximately mm/s) with low
      driving voltage of a few volts only. However, they also displayed many
      quantitative and qualitative discrepancies with existing theories. We therefore
      extend the latter theories to account for three experimentally relevant effects:
      (i) vertical confinement of the pumping channel, (ii) Faradaic currents from
      electrochemical reactions at the electrodes, and (iii) nonlinear surface
      capacitance of the Debye layer. We report here that these effects indeed affect
      the pump performance in a way that we can rationalize by physical arguments.

PMID- 16803044
TI  - Wave interaction in relativistic harmonic gyro-traveling-wave devices.
AB  - In gyro-traveling-wave devices, several waves can be excited at different
      cyclotron harmonics simultaneously. This paper analyzes the interaction between
      three waves synchronous with gyrating electrons at different cyclotron harmonics
      in two relativistic gyro-amplifier configurations; viz., gyro-traveling-wave
      tubes and gyrotwystrons. Two types of nonlinear interactions are considered: (a)
      excitation of two waves at cyclotron harmonics by a wave excited at the
      fundamental resonance, and (b) excitation of a wave at the fundamental resonance
      and another wave at the third harmonic by a wave excited at the second cyclotron
      harmonic. The effect of the overlapping of electron cyclotron resonances on the
      performance of relativistic gyrodevices is investigated as well.

PMID- 16803045
TI  - Nonlocal kinetics of the electrons in a low-pressure afterglow plasma.
AB  - Low-pressure pulsed plasmas are widely used in various technological
      applications. Understanding of the phenomena taking place in afterglow phase of
      the discharge makes possible the optimization of the operation conditions and
      improvement of the technical parameters. At low pressure the electron component
      of the plasma determines the main features of the discharge since its behavior
      dominates all other plasma properties. We study the electron kinetics in a low
      pressure afterglow plasma of an inductively coupled discharge by means of a self
      consistent model which uses the nonlocal kinetic approach. The main features of
      the model are given. Special attention is paid to determination of the steady
      state of the discharge from which the decay of the plasma begins. Emphasis is
      also put on the description of the collisional interaction between the electrons
      and gas. Results of theoretical investigations for argon at a pressure of 2-4 Pa
      are presented. Calculated temporal evolutions of the isotropic part of the
      electron velocity distribution function, electron density, mean electron energy,
      and wall potential are discussed in comparison with experimental data.

PMID- 16803046
TI  - Electronic structure and equation of state data of warm dense gold.
AB  - Equation of state data and electrical resistivity of warm dense gold were
      measured in the internal energy range 8 - 12 MJ/kg. Experimental results were
      compared with quantum molecular dynamics simulations. The theoretical results
      match well the experimental data, allowing a detailed interpretation of the
      theoretical thermodynamic properties and frequency-dependent conductivities.

PMID- 16803047
TI  - Zigzag transition of finite dust clusters.
AB  - Experiments on the zigzag transition of finite dust clusters are presented.
      There, microspheres have been confined in an anisotropic trap in the sheath of a
      radio-frequency discharge plasma. Transitions of the clusters from a linear chain
      into a zigzag configuration are observed by increasing the particle number in the
      chain or by variation of the anisotropy of the confinement. The equilibrium
      configurations of the finite clusters, as well as the dynamical properties and
      the stability behavior near the transition have been investigated from a normal
      mode analysis. Furthermore, the longitudinal and transverse dispersion of the
      normal modes in the one-dimensional (1D) chain has been derived.

PMID- 16803048
TI  - Neutral helium spectral lines in dense plasmas.
AB  - Shift and broadening of isolated neutral helium lines 7281 angstroms (2(1)P
      3(1)S), 7065 angstroms (2(3)P-3(3)S), 6678 angstroms (2(1)P-3(1)D), 5048
      angstroms (2(1)P-4(1)S), 4922 angstroms (2(1)P-4(1)D), and 4713 angstroms (2(3)P
      4(3)S) in a dense plasma are investigated. Based on a quantum statistical theory,
      the electronic contributions to the shift and width are considered, using the
      method of thermodynamic Green functions. Dynamic screening of the electron-atom
      interaction is included. Compared to the width, the electronic shift is more
      affected by dynamical screening. This effect increases at high density. A cut-off
      procedure for strong collisions is used. The contribution of the ions is taken
      into account in a quasi-static approximation, with both the quadratic Stark
      effect and the quadrupole interaction included. The results for shift and width
      agree well with the available experimental and theoretical data.

PMID- 16803049
TI  - Highly charged ions in a dilute plasma: an exact asymptotic solution involving
      strong coupling.
AB  - The ion sphere model introduced long ago by Salpeter is placed in a rigorous
      theoretical setting. The leading corrections to this model for very highly
      charged but dilute ions in thermal equilibrium with a weakly coupled, one
      component background plasma are explicitly computed, and the subleading
      corrections shown to be negligibly small. This is done using the effective field
      theory methods advocated by Brown and Yaffe. Thus, corrections to nuclear
      reaction rates that such highly charged ions may undergo can be computed
      precisely. Moreover, their contribution to the equation of state can also be
      computed with precision. Such analytic results for very strong coupling are
      rarely available, and they can serve as benchmarks for testing computer models in
      this limit.

PMID- 16803050
TI  - Crystal nucleation in the one-component plasma.
AB  - We have performed molecular dynamics simulations to study the kinetics of crystal
      nucleation in the one-component plasma. We have monitored nucleation in the
      supercooled liquid phase by following the time evolution of the size distribution
      of crystal nuclei formed during the phase transition. Although several
      observations are consistent with classical nucleation theory such as transient
      effects and the existence of a free-energy barrier to crystallization, we could
      not unambiguously identify a critical size for the crystal nuclei formed within
      the metastable phase.

PMID- 16803051
TI  - Coupled dipole method for radiation dynamics in finite photonic crystal
      structures.
AB  - We present a coupled-dipole treatment of radiation dynamics in the weak-coupling
      regime in a finite three-dimensional photonic crystal structure. The structure is
      discretized in real space and the self-consistent local field is computed. We
      illustrate the computation of radiation dynamics by calculating the spontaneous
      emission rate for a source located in a defect cavity inside a slab photonic
      crystal structure. We compute the cavity spectral response, the near-field modal
      structure, and the far-field radiation pattern of the microcavity. We also
      discuss our results in light of the recent experimental near-field observations
      of the optical modes of a photonic crystal microcavity.

PMID- 16803052
TI  - Partially coherent accessible solitons in strongly nonlocal media.
AB  - We study the propagation of incoherent accessible solitons in strongly nonlocal
      media with arbitrary response function. Based on the linear propagation equation
      and the mutual coherence function approach, we obtain an exact analytical
      solution of such incoherent accessible solitons. The solitons radius is related
      to the total power as well as the coherence characteristics of the incoherent
      beam. We find that there is not a threshold for incoherent solitons exist in
      strongly nonlocal media because the model is linear. Evolution behaviors of the
      solitons width and the coherence radius are also described when the solitons
      undergo linear harmonic oscillation.

PMID- 16803053
TI  - Domain wall dynamics in expanding spaces.
AB  - We study the effects on the dynamics of kinks due to expansions and contractions
      of the space. We show that the propagation velocity of the kink can be
      adiabatically tuned through slow expansions and/or contractions, while its width
      is given as a function of the velocity. We also analyze the case of fast
      expansions and/or contractions, where we are no longer on the adiabatic regime.
      In this case the kink moves more slowly after an expansion-contraction cycle as a
      consequence of the loss of energy through radiation. All these effects are
      numerically studied in the nonlinear Klein-Gordon equations (both for the sine
      Gordon and for the potential), and they are also studied within the framework of
      the collective coordinate evolution equations for the width and the center of
      mass of the kink. These collective coordinate evolution equations are obtained
      with a procedure that allows us to consider even the case of large expansions
      and/or contractions.

PMID- 16803054
TI  - Radiation pressure of light pulses and conservation of linear momentum in
      dispersive media.
AB  - We derive an expression for the Minkowski momentum under conditions of dispersive
      susceptibility and permeability, and compare it to the Abraham momentum in order
      to test the principle of conservation of linear momentum when matter is present.
      We investigate cases when an incident pulse interacts with a variety of
      structures, including thick substrates, resonant, free-standing, micron-sized
      multilayer stacks, and negative index materials. In general, we find that for
      media only a few wavelengths thick the Minkowski and Abraham momentum densities
      yield similar results. For more extended media, including substrates and Bragg
      mirrors embedded inside thick dielectric substrates, our calculations show
      dramatic differences between the Minkowski and Abraham momenta. Without
      exception, in all cases investigated the instantaneous Lorentz force exerted on
      the medium is consistent only with the rate of change of the Abraham momentum. As
      a practical example, we use our model to predict that electromagnetic momentum
      and energy buildup inside a multilayer stack can lead to widely tunable
      accelerations that may easily reach and exceed 10(10) m/s(2) for a mass of 10(-5)
      g. Our results suggest that the physics of the photonic band edge and other
      similar finite structures may be used as a testing ground for basic
      electromagnetic phenomena such as momentum transfer to macroscopic media.

PMID- 16803055
TI  - Effect of microscopic disorder on magnetic properties of metamaterials.
AB  - We analyze the effect of microscopic disorder on the macroscopic properties of
      composite metamaterials and study how weak statistically independent fluctuations
      of the parameters of the structure elements can modify their collective magnetic
      response and left-handed properties. We demonstrate that even a weak microscopic
      disorder may lead to a substantial modification of the metamaterial magnetic
      properties, and a 10% deviation in the parameters of the microscopic resonant
      elements may lead to a substantial suppression of the wave propagation in a wide
      frequency range. A noticeable suppression occurs also if more than 10% of the
      resonant magnetic elements possess strongly different properties, and in the
      latter case the defects can create an additional weak resonant line. These
      results are of a key importance for characterizing and optimizing novel composite
      metamaterials with the left-handed properties at terahertz and optical
      frequencies.

PMID- 16803056
TI  - Formation and propagation of coupled ultraslow optical soliton pairs in a cold
      three-state double- system.
AB  - We investigate the simultaneous formation and propagation of coupled ultraslow
      optical soliton pairs in a cold, lifetime-broadened three-state double-Lambda
      atomic system. Starting from the equations of motion of atomic response and two
      mode probe-control electromagnetic fields, we derive coupled nonlinear
      Schrodinger equations that govern the nonlinear evolution of the envelopes of the
      probe fields in this four-wave mixing scheme by means of the standard method of
      multiple scales. We demonstrate that for weak probe fields and with suitable
      operation conditions, a pair of coupled optical solitons moving with remarkably
      slow propagating velocity can be established in such a highly resonant atomic
      medium. The key elements to such a shape preserving, well matched yet interacting
      soliton pair is the balance between dispersion effect and self- and cross-phase
      modulation effects of the system.

PMID- 16803057
TI  - Resolution of subwavelength transmission devices formed by a wire medium.
AB  - The restrictions on the resolution of transmission devices formed by wire media
      (arrays of conductive cylinders) recently proposed in Phys. Rev. B 71, 193105
      (2005) and experimentally tested in Phys. Rev. B 73, 033108 (2006) are studied in
      this paper using both analytical and numerical modeling. It is demonstrated that
      such transmission devices have subwavelength resolution that can in principle be
      made as fine as required by a specific application by controlling the lattice
      constant of the wire medium. This confirms that slabs of the wire medium are
      unique imaging devices at the microwave frequency range, and are capable of
      transmitting distributions of TM-polarized electric fields with nearly unlimited
      subwavelength resolution to practically arbitrary distances.

PMID- 16803058
TI  - Incoherent white-light solitons in nonlinear periodic lattices.
AB  - We predict the existence of lattice solitons made of incoherent white light:
      lattice solitons made of light originating from an ordinary incandescent light
      bulb. We find that the intensity structure and spatial power spectra associated
      with different temporal frequency constituents of incoherent white-light lattice
      solitons (IWLLSs) arrange themselves in a characteristic fashion, with the
      intensity structure more localized at higher frequencies, and the spatial power
      spectrum more localized at lower frequencies; the spatial correlation distance is
      larger at lower frequency constituents of IWLLSs. This characteristic shape of
      incoherent white-light lattice solitons reflects the fact that diffraction is
      stronger for lower temporal frequency constituents, while higher frequencies
      experience stronger effective nonlinearity and deeper lattice structure.

PMID- 16803059
TI  - Energy localization in the phi4 oscillator chain.
AB  - We study energy localization in a finite one-dimensional phi(4) oscillator chain
      with initial energy in a single oscillator of the chain. We numerically calculate
      the effective number of degrees of freedom sharing the energy on the lattice as a
      function of time. We find that for energies smaller than a critical value, energy
      equipartition among the oscillators is reached in a relatively short time. On the
      other hand, above the critical energy, a decreasing number of particles sharing
      the energy is observed. We give an estimate of the effective number of degrees of
      freedom as a function of the energy. Our results suggest that localization is due
      to the appearance, above threshold, of a breather-like structure. Analytic
      arguments are given, based on the averaging theory and the analysis of a discrete
      nonlinear Schrodinger equation approximating the dynamics, to support and explain
      the numerical results.

PMID- 16803060
TI  - Persistent breathers in long-ranged discrete nonlinear Schrodinger models.
AB  - The DNLS model including Kac-Baker long-range interactions and nonlinear damping
      exhibits prominent effects in computer simulations. The combination of long-range
      forces and damping yields a periodic pattern of stationary breathers from an
      originally uniformly distributed background. The inverse interaction radius
      determines the periodicity which can be understood in the quasicontinuum
      approximation of the system. For the undamped system, we investigate the impact
      of the long-range interactions on the transition to the persistent-breather
      phase, which only depends on the energy and the norm of the DNLS. Using Monte
      Carlo techniques, we can monitor the localization strength as a function of the
      the long-range radius and the system temperature, which is formally negative in
      the persistent-breather phase.

PMID- 16803061
TI  - Class of solitary wave solutions of the one-dimensional Gross-Pitaevskii
      equation.
AB  - We present a large family of exact solitary wave solutions of the one-dimensional
      Gross-Pitaevskii equation, with time-varying scattering length and gain or loss,
      in both expulsive and regular parabolic confinement regimes. The consistency
      condition governing the soliton profiles is shown to map onto a linear
      Schrodinger eigenvalue problem, thereby enabling one to find analytically the
      effect of a wide variety of temporal variations in the control parameters, which
      are experimentally realizable. Corresponding to each solvable quantum mechanical
      system, one can identify a soliton configuration. These include soliton trains in
      close analogy to experimental observations of Streckeret al. [Nature (London)
      417, 150 (2002)], spatiotemporal dynamics, solitons undergoing rapid
      amplification, collapse and revival of condensates, and analytical expression of
      two-soliton bound states, to name a few.

PMID- 16803062
TI  - Near-field dynamics of ultrashort pulsed Bessel beams in media with Kerr
      nonlinearity.
AB  - The near-field dynamics of a femtosecond Bessel beam propagating in a Kerr
      nonlinear medium (fused silica) is investigated both numerically and
      experimentally. We demonstrate that the input Bessel beam experiences strong
      nonlinear reshaping. Due to the combined action of self-focusing and nonlinear
      losses the reshaped beam exhibits a radial compression and reduced visibility of
      the Bessel oscillations. Moreover, we show that the reshaping process starts from
      the intense central core and gradually replaces the Bessel beam profile during
      propagation, highlighting the conical geometry of the energy flow.

PMID- 16803063
TI  - Electromagnetic energy flux vector for a dispersive linear medium.
AB  - The electromagnetic energy flux vector in a dispersive linear medium is derived
      from energy conservation and microscopic quantum electrodynamics and is found to
      be of the Umov form as the product of an electromagnetic energy density and a
      velocity vector.

PMID- 16803064
TI  - Modes of nonlinear acoustic transparency in the strained paramagnetic crystal.
AB  - The propagation of transverse-longitudinal acoustic pulses through a strained
      cubic crystal containing resonant paramagnetic impurities with effective spin S
      =1 is investigated. It is supposed that the pulses propagate under arbitrary
      angle with respect to the direction of the external static deformation parallel
      to the fourth-order symmetry axis. In this geometry, both the transverse and
      longitudinal components of the acoustic field have high-frequency and zero
      frequency spectral components. We show that a pulse can propagate in modes
      different from the acoustic self-induced transparency. In particular, a pulse
      propagating in the mode of an acoustic self-induced supertransparency
      substantially changes the populations of the spin sublevels, but its group
      velocity remains almost equal to the linear velocity of the sound. If a pulse
      propagates in the acoustic extraordinary transparency mode, then its group
      velocity is substantially lower while the sublevel populations remain virtually
      invariant. Also, the modes of propagation under conditions of weakly excited spin
      transitions and large detuning of the pulse high-frequency components are
      identified.

PMID- 16803065
TI  - Disorder effect on the focus image of sonic crystals in air.
AB  - When acoustic waves propagate in two-dimensional sonic crystals composed of
      parallel rigid cylinders in air, anisotropic band gaps, such as a partial gap and
      deaf band, forbid the waves within certain frequency regions from propagating
      along certain directions, thus forming a stable imaging focus effect. If the
      introduced disorder has not destroyed the original anisotropic band gap, this
      unique effect still exists, although the focused image becomes blurred. Once the
      sample reaches complete disorder, the anisotropic band gap is destroyed, and this
      effect also disappears.

PMID- 16803066
TI  - Statistics of the eigenmodes and optical properties of one-dimensional disordered
      photonic crystals.
AB  - The eigenmode spectrum and transmission properties of a certain class of one
      dimensional disordered photonic crystals have been studied statistically. It is
      shown that the relative fluctuation of the optical width of the period of the
      photonic crystal is a universal parameter allowing a quantitative description of
      the disordered photonic crystal for various models of disorder. It is shown that
      the tail of the density of states is characterized by a certain penetration depth
      and a quantitative relation between the penetration depth, the relative band gap
      width, and the disorder parameter is obtained. It is found that a threshold level
      of disorder exists, below which the density of states in the center of the
      photonic band gap vanishes, and the ensemble-averaged transmission coefficient
      does not change significantly with increasing disorder. Also, the standard
      deviation of the transmission coefficient is less than its mean value. Above
      threshold, the ensemble averaged transmission coefficient and density of states
      increase with the level of disorder rapidly, and the standard deviation of the
      transmission coefficient exceeds its mean value. A scaling formula is presented,
      which relates the logarithm of the transmission to the periodic refractive index
      modulation and the disorder.

PMID- 16803067
TI  - Large positive and negative lateral optical beam shift in prism-waveguide
      coupling system.
AB  - In this paper, the lateral beam shift in a prism-waveguide coupling system at
      wavelengths ranging from visible to near infrared is theoretically examined. A
      simple theoretical formula is derived to analyze the behavior of the beam shift.
      We demonstrate that large positive and negative lateral optical beam shifts can
      be obtained when guided modes are excited. It is also found that the magnitude of
      the beam shift is closely related to the intrinsic and radiative damping. When
      the intrinsic damping is larger than the radiative damping, negative lateral beam
      shift occurs. Numerical calculations confirm the theoretical analysis and show
      that a beam shift of the order of millimeters is possible.

PMID- 16803068
TI  - Simulation of the density of states in isothermal and adiabatic ensembles.
AB  - This paper provides a unified treatment of the fundamental methods used to obtain
      the density of states via molecular simulations with isothermal ensembles (IEs)
      and adiabatic ensembles (AEs). Our analysis and results show that provides a
      natural bridge to go back and forth between IE and AE simulation data. They also
      underline the difference between the density of states of potential energy
      macrostates and that of total energy macrostates Omega, even though both provide
      access to the thermodynamic properties of the system. Visited-states approaches
      and transition matrix methods are described and applied to the Lennard-Jones
      fluid to target omega and Omega as functions of energy and volume macrostates. It
      is shown that one can obtain omega via a generalized acceptance-ratio formula
      that is applicable regardless of the conditions at which the ensemble is
      simulated. In this way, one can obtain while performing conventional IE or AE
      simulations, and do it at no extra cost and with a higher accuracy than is
      achievable with histogram methods.

PMID- 16803069
TI  - From the continuous to the lattice Boltzmann equation: the discretization problem
      and thermal models.
AB  - The velocity discretization is a critical step in deriving the lattice Boltzmann
      (LBE) from the continuous Boltzmann equation. This problem is considered in the
      present paper, following an alternative approach and giving the minimal discrete
      velocity sets in accordance with the order of approximation that is required for
      the LBE with respect to the continuous Boltzmann equation and with the lattice
      structure. Considering to be the order of the polynomial approximation to the
      Maxwell-Boltzmann equilibrium distribution, it is shown that solving the
      discretization problem is equivalent to finding the inner product in the discrete
      space induced by the inner product in the continuous space that preserves the
      norm and the orthogonality of the Hermite polynomial tensors in the Hilbert space
      generated by the functions that map the velocity space onto the real numbers
      space. As a consequence, it is shown that, for each order N of approximation, the
      even-parity velocity tensors are isotropic up to rank 2N in the discrete space.
      The norm and the orthogonality restrictions lead to space-filling lattices with
      increased dimensionality when compared with presently known lattices. This
      problem is discussed in relation with a discretization approach based on a finite
      set of orthogonal functions in the discrete space. Two-dimensional square
      lattices intended to be used in thermal problems and their respective equilibrium
      distributions are presented and discussed.

PMID- 16803070
TI  - Quantum Monte Carlo simulation in the canonical ensemble at finite temperature.
AB  - A quantum Monte Carlo method with a nonlocal update scheme is presented. The
      method is based on a path-integral decomposition and a worm operator which is
      local in imaginary time. It generates states with a fixed number of particles and
      respects other exact symmetries. Observables like the equal-time Green's function
      can be evaluated in an efficient way. To demonstrate the versatility of the
      method, results for the one-dimensional Bose-Hubbard model and a nuclear pairing
      model are presented. Within the context of the Bose-Hubbard model the efficiency
      of the algorithm is discussed.

PMID- 16803071
TI  - Performances of Wang-Landau algorithms for continuous systems.
AB  - The relative performances of different implementations of the Wang-Landau method
      are assessed on two classes of systems with continuous degrees of freedom,
      namely, two polypeptides and two atomic Lennard-Jones clusters. Parallel
      tempering Monte Carlo simulations serve as a reference, and we pay particular
      attention to the variations of the multiplicative factor f during the course of
      the simulation. For the systems studied, the Wang-Landau method is found to be of
      comparable accuracy as parallel tempering, but has significant difficulties in
      reproducing low-temperature transitions exhibited by the Lennard-Jones clusters
      at low temperature. Using a complementary order parameter and calculating a two
      dimensional joint density of states significantly improves the situation,
      especially for the notoriously difficult LJ(38) system. However, while parallel
      tempering easily converges for LJ(31), we have not been able to get data of
      comparable accuracy with Wang-Landau multicanonical sampling.

PMID- 16803072
TI  - Semi-implicit-linearized multiple-relaxation-time formulation of lattice
      Boltzmann schemes for mixture modeling.
AB  - A lattice Boltzmann model for mixture modeling is developed by applying the
      multiple-relaxation-time (MRT) approach to the Hamel model, which allows one to
      derive from a general framework different model equations independently proposed,
      like the Gross-Krook model and the Sirovich model. By imposing some physical
      constraints, the MRT lattice-Boltzmann Hamel model reduces to the generalized MRT
      lattice-Boltzmann Gross-Krook model (involving the local Maxwellian centered on
      the barycentric velocity), which allows one to tune independently the species
      diffusivity, the mixture kinematic viscosity, and the mixture bulk viscosity.
      Reducing the number of moving particles over the total is possible to deal
      effectively with mass particle ratios far from unity and, for this reason, to
      model the pressure-driven diffusion. A convenient numerical approach is proposed
      for solving the developed model, which essentially widens the stability range of
      conventional schemes in terms of dimensionless relaxation frequencies, by solving
      explicitly the advection operator together with the nonlinear terms of the
      collisional operator and solving implicitly the residual linear terms. In this
      way, the calculations are drastically reduced and the operative matrices can be
      computed once for all, at the beginning of the calculation (implying moderate
      additional computational demand). Following this approach, a semi-implicit
      linearized backward Euler scheme, ideal for parallel implementations, is
      proposed. In order to achieve the previous results, the asymptotic analysis,
      recently suggested for analyzing the macroscopic equations corresponding to
      lattice-Boltzmann schemes in the low-Mach-number limit, proves to be an effective
      tool. Some numerical tests are reported for proving the consistency of the
      proposed method with both the Fick model and Maxwell-Stefan model in the
      macroscopic limit.

PMID- 16803073
TI  - Population size bias in descendant-weighted diffusion quantum Monte Carlo
      simulations.
AB  - We consider the influence of population size on the accuracy of diffusion quantum
      Monte Carlo simulations that employ descendant weighting or forward walking
      techniques to compute expectation values of observables that do not commute with
      the Hamiltonian. We show that for a simple model system, the d-dimensional
      isotropic harmonic oscillator, the population size must increase rapidly with d
      in order to ensure that the simulations produce accurate results. When the
      population size is too small, expectation values computed using descendant
      weighted diffusion quantum Monte Carlo simulations exhibit significant systematic
      biases.

PMID- 16803074
TI  - Coarse-grained simulation of chaotic mixing in laminar flows.
AB  - A model for chaotic mixing has been formulated and tested. The advection of a
      passive scalar by laminar flows with high Peclet numbers is modeled by a finite
      volume method on a coarse grid. The scales which are smaller than the increment
      of the grid are modeled by an approximate subgrid model. The artificial
      diffusivity of the finite-difference method plays a twofold role. It prevents the
      formation of spurious oscillations of the solution and also models the transport
      of the variation of the scalar from the large to subgrid modes.

PMID- 16803075
TI  - Improved simulation of drop dynamics in a shear flow at low Reynolds and
      capillary number.
AB  - The simulation of multicomponent fluids at low Reynolds number and low capillary
      number is of interest in a variety of applications such as the modeling of venule
      scale blood flow and microfluidics; however, such simulations are computationally
      demanding. An improved multicomponent lattice Boltzmann scheme, designed to
      represent interfaces in the continuum approximation, is presented and shown (i)
      significantly to reduce common algorithmic artifacts and (ii) to recover full
      Galilean invariance. The method is used to model drop dynamics in shear flow in
      two dimensions where it recovers correct results over a range of Reynolds and
      capillary number greater than that which may be addressed with previous methods.

PMID- 16803076
TI  - Global persistence exponent of the double-exchange model.
AB  - We obtained the global persistence exponent for a continuous spin model on the
      simple cubic lattice with double-exchange interaction by using two different
      methods. First, we estimated the exponent theta(g) by following the time
      evolution of probability P(t) that the order parameter of the model does not
      change its sign up to time t[P(t) approximately t(-theta(g)]. Afterwards, that
      exponent was estimated through the scaling collapse of the universal function
      L(theta(g)(z)P(t) for different lattice sizes. Our results for both approaches
      are in very good agreement with each other.

PMID- 16803077
TI  - Mean number of visits to sites in Levy flights.
AB  - Formulas are derived to compute the mean number of times a site has been visited
      during symmetric Levy flights. Unrestricted Levy flights are considered first,
      for lattices of any dimension: conditions for the existence of finite asymptotic
      maps of the visits over the lattice are analyzed and a connection is made with
      the transience of the flight. In particular it is shown that flights on lattices
      of dimension greater than 1 are always transient. For an interval with absorbing
      boundaries the mean number of visits reaches stationary values, which are
      computed by means of numerical and analytical methods; comparisons with Monte
      Carlo simulations are also presented.

PMID- 16803078
TI  - Linear irreversible thermodynamics and coefficient of performance.
AB  - Following the recent proposal by Van den Broeck for a heat engine [Phys. Rev.
      Lett. 95, 190602 (2005)], we analyze the coefficient of performance of a
      refrigerator in two working regimes using the tools of linear irreversible
      thermodynamics. In particular, one of the analyzed regimes gives a coefficient of
      performance which could be considered as the equivalent to the Curzon-Ahlborn
      efficiency. Also we consider the relation with the Clausius inequality, and some
      results for the relevant thermodynamic magnitudes in this formalism are
      confronted with those obtained using the finite-time thermodynamics framework.

PMID- 16803079
TI  - Early time evolution of Freedericksz patterns generated from states of
      electroconvection.
AB  - We report on the early time ordering in a nematic liquid crystal subjected to a
      sudden change in an external ac electric field. We compare time evolution for two
      different initial states of electroconvection. Electroconvection is a highly
      driven state of a nematic liquid crystal involving convective motion of the fluid
      and periodic variations of the molecular alignment. By suddenly changing either
      the voltage or the frequency of the applied ac field, the system is brought to
      the same thermodynamic conditions. The time ordering of the system is
      characterized by the evolution of features of the power spectrum, including the
      average wave number, total power, and shape of the power spectrum. We observe
      that ordering of the system occurs faster after a sudden change in frequency than
      it does after a sudden change in voltage.

PMID- 16803080
TI  - Quantum chaotic patterns in the E (b1 + b2) Jahn-Teller model.
AB  - We study statistical properties of excited levels of the E (b(1) + b(2) Jahn
      Teller model. The multitude of avoided crossings of energy levels is generally
      claimed to be a testimony of quantum chaos. We found that apart from two limiting
      cases (E e and Holstein model) the distribution of nearest-neighbor spacings is
      rather stable as to the change of parameters and different from the Wigner one.
      This limiting distribution assumably shows approximately radical S scaling at
      small and resembles the semi-Poisson law P(S) = 4S exp(-2S) at S > or = 1. The
      latter is believed to be universal and characteristic, e.g., at the transition
      between metal and insulator phases.

PMID- 16803081
TI  - Antiphase synchronization in coupled chaotic oscillators.
AB  - Anti-phase synchronization (AS) in coupled chaotic oscillators is investigated.
      The necessary condition for AS is given and the stability of AS is studied.
      Results are demonstrated with numerical simulations and electronic circuits.

PMID- 16803082
TI  - Generation of sub-Mbar pressure by converging shock waves produced by the
      underwater electrical explosion of a wire array.
AB  - We report a demonstration of a generation of sub-Mbar pressure on the axis of the
      implosion wave produced by an underwater electrical explosion of a cylindrical
      wire array. The array was exploded by microsecond time scale discharge of a
      capacitor bank having a stored energy of 4.5 kJ and discharge current amplitude
      of up to 90 kA. Optical diagnostics were used to determine the time of flight and
      the trajectory of the converging shock wave. This data were applied for a
      calculation of the water flow parameters using one-dimensional (1D) and 2D
      hydrodynamic calculations and the Whitham method. All three methods have shown
      that the shock wave pressure at 0.1 mm from the axis reaches .

PMID- 16803083
TI  - Modulational instability of partially coherent signals in electrical transmission
      lines.
AB  - We present an investigation of the modulational instability of partially coherent
      signals in electrical transmission lines. Starting from the modified Ginzburg
      Landau equations and the Wigner-Moyal representation, we derive a nonlinear
      dispersion relation for the modulational instability. It is found that the effect
      of signal broadbandness reduces the growth rate of the modulational instability.

PMID- 16803084
TI  - Undular bore solution of the Camassa-Holm equation.
AB  - Modulation theory is developed for a periodic peakon solution of the Camassa-Holm
      equation. An explicit simple wave solution of these modulation equations is then
      derived; this simple wave describing the evolution into an undular bore of an
      initial step. The characteristic on which the expansion fan occurs (propagating
      at a nonlinear group velocity) has a turning point, illustrating the fact that
      there is a minimum nonlinear group velocity at which the waves can propagate. A
      linear analytical solution, based on an integral of the Airy function, is then
      derived to describe the evanescent portion of the undular bore behind the turning
      point. Good agreement is found between the modulation theory plus Airy integral
      solution and numerical solutions.

PMID- 16803085
TI  - Comment on "Maximal planar networks with large clustering coefficient and power
      law degree distribution".
AB  - This Comment corrects the error which appeared in the calculation of the degree
      distribution of random Apollonian networks [T. Zhou, G. Yan, and B. H. Wang,
      Phys. Rev. E. 71, 046141 (2005)]. As a result, the expression of P(k), which
      gives the probability that a randomly selected node has exactly k edges, has the
      form P(k) alpha 1/[k(k + 1)(k + 2)].

PMID- 16803087
TI  - Integrable nonlinear evolution partial differential equations in 4 + 2 and 3 + 1
      dimensions.
AB  - The derivation and solution of integrable nonlinear evolution partial
      differential equations in three spatial dimensions has been the holy grail in the
      field of integrability since the late 1970s. The celebrated Korteweg-de Vries and
      nonlinear Schrodinger equations, as well as the Kadomtsev-Petviashvili (KP) and
      Davey-Stewartson (DS) equations, are prototypical examples of integrable
      evolution equations in one and two spatial dimensions, respectively. Do there
      exist integrable analogs of these equations in three spatial dimensions? In what
      follows, I present a positive answer to this question. In particular, I first
      present integrable generalizations of the KP and DS equations, which are
      formulated in four spatial dimensions and which have the novelty that they
      involve complex time. I then impose the requirement of real time, which implies a
      reduction to three spatial dimensions. I also present a method of solution.

PMID- 16803088
TI  - Quantum magnetism with multicomponent dipolar molecules in an optical lattice.
AB  - We consider bosonic dipolar molecules in an optical lattice prepared in a mixture
      of different rotational states. The 1/R(3) interaction between molecules for this
      system is produced by exchanging a quantum of angular momentum between two
      molecules. We show that the Mott states of such systems have a large variety of
      quantum phases characterized by dipolar orderings including a state with an
      ordering wave vector that can be changed by tilting the lattice. As the Mott
      insulating phase is melted, we also describe several exotic superfluid phases
      that will occur.

PMID- 16803089
TI  - Phase diagram of Bose-Fermi mixtures in one-dimensional optical lattices.
AB  - The ground state phase diagram of the one-dimensional Bose-Fermi Hubbard model is
      studied in the canonical ensemble using a quantum Monte Carlo method. We focus on
      the case where both species have half filling in order to maximize the pairing
      correlations between the bosons and the fermions. In case of equal hopping we
      distinguish among phase separation, a Luttinger liquid phase, and a phase
      characterized by strong singlet pairing between the species. True long-range
      density waves exist with unequal hopping amplitudes.

PMID- 16803090
TI  - Spin-3 chromium Bose-Einstein condensates.
AB  - We analyze the physics of spin-3 Bose-Einstein condensates, and, in particular,
      the new physics expected in ongoing experiments with condensates of chromium
      atoms. We first discuss the ground-state properties, which, depending on still
      unknown chromium parameters, and for low magnetic fields, can present various
      types of phases. We also discuss the spinor dynamics in chromium spinor
      condensates, which present significant qualitative differences when compared to
      other spinor condensates. In particular, dipole-induced spin relaxation may lead
      for low magnetic fields to transfer of spin into angular momentum similar to the
      well-known Einstein-de Haas effect. Additionally, a rapid large transference of
      population between distant magnetic states also becomes possible.

PMID- 16803091
TI  - 52Cr spinor condensate: a biaxial or uniaxial spin nematic.
AB  - We show that the newly discovered 52Cr Bose condensate in zero magnetic field can
      be a spin nematic of the following kind: a "maximum" polar state, a "colinear"
      polar state, or a biaxial nematic ferromagnetic state. We also present the phase
      diagram with a magnetic field in the interaction subspace containing the chromium
      condensate. It contains many uniaxial and biaxial spin nematic phases, which
      often but not always break time reversal symmetry, and can exist with or without
      spontaneous magnetization.

PMID- 16803092
TI  - Complete deterministic linear optics Bell state analysis.
AB  - We show how hyperentanglement allows us to deterministically distinguish between
      all four polarization Bell states of two photons. In this proof-of-principle
      experiment, we employ the intrinsic time-energy correlation of photon pairs
      generated with high temporal definition in addition to the polarization
      entanglement obtained from parametric down-conversion. For the identification, no
      nonlinear optical elements or auxiliary photons are needed. The new possibilities
      this complete Bell measurement offers are demonstrated by realizing an optimal
      dense coding protocol.

PMID- 16803093
TI  - Giant colloidal diffusivity on corrugated optical vortices.
AB  - A single colloidal sphere circulating around a periodically modulated optical
      vortex trap can enter a dynamical state in which it intermittently alternates
      between freely running around the ringlike optical vortex and becoming trapped in
      local potential energy minima. Velocity fluctuations in this randomly switching
      state still are characterized by a linear Einstein-like diffusion law, but with
      an effective diffusion coefficient that is enhanced by more than 2 orders of
      magnitude.

PMID- 16803094
TI  - Demonstration of a controllable three-dimensional Brownian motor in symmetric
      potentials.
AB  - We demonstrate a Brownian motor, based on cold atoms in optical lattices, where
      isotropic random fluctuations are rectified in order to induce controlled atomic
      motion in arbitrary directions. In contrast to earlier demonstrations of ratchet
      effects, our Brownian motor operates in potentials that are spatially and
      temporally symmetric, but where spatiotemporal symmetry is broken by a phase
      shift between the potentials and asymmetric transfer rates between them. The
      Brownian motor is demonstrated in three dimensions and the noise-induced drift is
      controllable in our system.

PMID- 16803095
TI  - Hidden supersymmetry of domain walls and cosmologies.
AB  - We show that all domain-wall solutions of gravity coupled to scalar fields for
      which the world-volume geometry is Minkowski or anti-de Sitter admit Killing
      spinors, and satisfy corresponding first-order equations involving a
      superpotential determined by the solution. By analytic continuation, all flat or
      closed Friedmann-Lemaitre-Robertson-Walker cosmologies are shown to satisfy
      similar first-order equations arising from the existence of "pseudo Killing"
      spinors.

PMID- 16803096
TI  - Dipole of the luminosity distance: a direct measure of H(z).
AB  - We show that the dipole of the luminosity distance is a useful observational tool
      which allows us to determine the Hubble parameter as a function of redshift H(z).
      We determine the number of supernovae needed to achieve a given precision for
      H(z) and to distinguish between different models for dark energy. We analyze a
      sample of nearby supernovae and find a dipole consistent with the cosmic
      microwave background at a significance of more than 2alpha.

PMID- 16803098
TI  - Clean prediction of CP-violating processes psi, phi, and Gamma decay to KSKS and
      KLKL.
AB  - The ratio of K(S)K(S) (K(L)K(L)) and K(L)K(L) production rates is calculated by
      considering K(0) - K(0) oscillation in J/psi --> K(0)K(0) decay. The theoretical
      uncertainty due to strong interaction in J/psi decay is completely canceled in
      the ratio; therefore, the absolute branching fractions of the CP-violating
      processes of J/psi --> K(S)K(S) and K(L)K(L) can be cleanly and model
      independently determined in the case that J/psi K(S)K(L) decay is precisely
      measured. In the future tau-charm factory, the expected CP violating process of
      J/psi --> K(S)K(S) should be reached. It is important to measure J/psi to
      K(S)K(S) and K(S)K(L) decays simultaneously, so that many systematic errors will
      be canceled. More precise measurements are suggested to examine the predicted
      isospin relation in J/psi --> KK decays. All results can be extended to decays of
      other vector quarkonia, phi, psi(2S), and gamma(1S), etc.

PMID- 16803099
TI  - Partial photoneutron cross sections for the isomeric state 180Tam.
AB  - Photoneutron cross sections for (181)Ta(y, n) (180)Ta(m) were determined from
      simultaneous measurements of total cross sections (sigma(tot) and ground-state
      cross sections (sigma(gs)) for (180)Ta in photodisintegration of with laser
      Compton-backscattered rays. Techniques of direct neutron counting and
      photoactivation were used for the measurement of sigma(tot) and sigma(gs),
      respectively. The partial cross sections for the isomeric state serves as a novel
      probe of the nuclear level density of (180)Ta. Implications for the p- and s
      process nucleosynthesis of (180)Ta(m) are given.

PMID- 16803100
TI  - Signatures for multi-alpha-condensed states.
AB  - An experimental way of testing Bose-Einstein condensation of alpha clusters in
      the atomic nucleus is reported. The enhancement of cluster emission and the
      multiplicity partition of possible emitted clusters could be direct signatures
      for the condensed states. The barrier for the emission of clusters, such as (8)Be
      and (12)C(O(+)(2)), is calculated and compared with the barrier for the
      sequential emission of 2 or 3alpha particles from the compound nucleus. For the
      calculations, a simple approach using a folded Woods-Saxon potential is used.

PMID- 16803101
TI  - Electric quadrupole moments of the D states of alkaline-earth-metal ions.
AB  - The electric quadrupole moment for the 4d(2)D(5/2) state of (88)Sr(+); one of the
      most important candidates for an optical clock, has been calculated using the
      relativistic coupled-cluster theory. This is the first application of this theory
      to determine atomic electric quadrupole moments. The result of the calculation is
      presented and the important many-body contributions are highlighted. The
      calculated electric quadrupole moment is (2.94 +/- 0.07)ea(2)(0), where a(o) is
      the Bohr radius and the electronic charge while the measured value is (2.6 +/-
      0.3) ea(2)(0). This is so far the most accurate determination of the electric
      quadrupole moment for the above mentioned state. We have also calculated the
      electric quadrupole moments for the metastable 4d(2)D(3/2) state of 88(Sr(+) and
      for the 3d(2)D(3/2.5/2) and 5d(2)D(3/2.5/2) states of (43)Ca(+) and (138)Ba(+),
      respectively.

PMID- 16803102
TI  - Conical emission, pulse splitting, and X-wave parametric amplification in
      nonlinear dynamics of ultrashort light pulses.
AB  - The precise observation of the angle-frequency spectrum of light filaments in
      water reveals a scenario incompatible with current models of conical emission
      (CE). Its description in terms of linear X-wave modes leads us to understand
      filamentation dynamics requiring a phase- and group-matched, Kerr-driven four
      wave-mixing process that involves two highly localized pumps and two X waves. CE
      and temporal splitting arise naturally as two manifestations of this process.

PMID- 16803103
TI  - Determination of a coupling function in multicoupled oscillators.
AB  - A new method to determine a coupling function in a phase model is theoretically
      derived for coupled self-sustained oscillators and applied to Belousov
      Zhabotinsky (BZ) oscillators. The synchronous behavior of two coupled BZ reactors
      is explained extremely well in terms of the coupling function thus obtained. This
      method is expected to be applicable to weakly coupled multioscillator systems, in
      which mutual coupling among nearly identical oscillators occurs in a similar
      manner. The importance of higher-order harmonic terms involved in the coupling
      function is also discussed.

PMID- 16803104
TI  - Bulk flow in ferrofluids in a uniform rotating magnetic field.
AB  - Direct measurements of the bulk flow of a ferrofluid in a uniform rotating
      magnetic field were obtained using the ultrasonic velocity profile method. The
      fluid was observed to corotate with the field in a rigid-body-like fashion
      throughout the bulk of the container, except near the air-fluid interface, where
      it was observed to counterrotate. The results were found in qualitative agreement
      with the spin diffusion theory of Zaitsev and Shliomis [J. Appl. Mech. Tech.
      Phys. 10, 696 (1969)]10.1007/BF00907424.

PMID- 16803105
TI  - Creation of hot radiation environments in laser-driven targets.
AB  - A hot radiation environment, produced by maximizing laser-energy deposition into
      a small, high- "can," is a platform being developed for investigations of
      material properties under extreme conditions. In such small targets, almost
      doubling the laser energy results in only an incremental increase in the x
      radiation flux, and almost no increase in the maximum achieved radiation
      temperature. That most of this additional laser energy is not deposited within
      the target is a direct consequence of laser-plasma interactions (LPI) outside of
      the target, which result in high-angle beams never entering the target late in
      the laser pulse. Accounting for these processes in the modeling results in
      quantitative agreement for the first time with experiments using very small cans.
      These findings have provided the scientific foundation for modifying the target
      geometry to mitigate the LPI and to achieve higher radiation temperatures.

PMID- 16803106
TI  - Observation of turbulent-driven shear flow in a cylindrical laboratory plasma
      device.
AB  - An azimuthally symmetric radially sheared plasma fluid flow is observed to
      spontaneously form in a cylindrical magnetized helicon plasma device with no
      external sources of momentum input. A turbulent momentum conservation analysis
      shows that this shear flow is sustained by the Reynolds stress generated by
      collisional drift turbulence in the device. The results provide direct
      experimental support for the basic theoretical picture of drift-wave-shear-flow
      interactions.

PMID- 16803108
TI  - Comparison study of 2D images of temperature fluctuations during sawtooth
      oscillation with theoretical models.
AB  - High temporal and spatial resolution two-dimensional (2D) images of electron
      temperature fluctuations were employed to study the sawtooth oscillation in the
      Toroidal Experiment for Technically Oriented Research tokamak plasmas. The 2D
      images are directly compared with the expected 2D patterns of the plasma pressure
      (or electron temperature) from various theoretical models. The observed
      experimental 2D images are only partially in agreement with the expected patterns
      from each model: The image of the initial reconnection process is similar to that
      of the ballooning mode model. The intermediate and final stages of the
      reconnection process resemble those of the full reconnection model. The time
      evolution of the images of the hot spot or island is partially consistent to
      those from the full reconnection model but is not consistent with those from the
      quasi-interchange model.

PMID- 16803107
TI  - Observation of high-field-side crash and heat transfer during sawtooth
      oscillation in magnetically confined plasmas.
AB  - High resolution (temporal and spatial), two-dimensional images of electron
      temperature fluctuations during sawtooth oscillations were employed to study the
      crash process and heat transfer in magnetically confined toroidal plasmas. The
      combination of kink and local pressure driven instabilities leads to a small
      poloidally localized puncture in the magnetic surface at both the low and the
      high field sides of the poloidal plane. This observation closely resembles the
      "fingering event" of the ballooning mode model with the high- mode only predicted
      at the low field side.

PMID- 16803109
TI  - Phase transitions in solids stimulated by simultaneous exposure to high pressure
      and relativistic heavy ions.
AB  - In many solids, heavy ions of high kinetic energy (MeV-GeV) produce long
      cylindrical damage trails with diameters of order 10 nm. Up to now, no
      information was available how solids cope with the simultaneous exposure to these
      energetic projectiles and to high pressure. We report the first experiments where
      relativistic uranium and gold ions from the SIS heavy-ion synchrotron at GSI were
      injected through several mm of diamond into solid samples pressurized up to 14
      GPa in a diamond anvil cell. In synthetic graphite and natural zircon, the
      combination of pressure and ion beams triggered drastic structural changes not
      caused by the applied pressure or the ions alone. The modifications comprise long
      range amorphization of graphite rather than individual track formation, and in
      the case of zircon the decomposition into nanocrystals and nucleation of the high
      pressure phase reidite.

PMID- 16803110
TI  - Birth and morphological evolution of step bunches under electromigration.
AB  - We analyze the dynamics of electromigration-induced step bunching in the absence
      of desorption. We show that, even when the instability occurs at long wavelength,
      hinting to a smooth morphology, the surface suddenly splits into bunches escorted
      with wide terraces, in agreement with several observations. As the size of the
      bunches increases, a nonstandard regime is exhibited, namely, the bunches do not
      match tangentially to the facet, as would the classical Pokrosvky-Talapov shape
      dictate. This Letter presents a complete scenario of evolution of bunches from
      their birth up to their ultimate stage.

PMID- 16803111
TI  - Similarities in the Cp/T3 peaks in amorphous and crystalline metals.
AB  - A low-temperature peak in C(p)/T(3) vs is ubiquitous to glasses. It arises from
      an abundance of low-frequency vibrations, the origin of which remains unclear. A
      comparable C(p)/T(3) vs peak is observed in crystals due to the dispersion of
      acoustic phonons and/or the excitation of optical phonons. We compared the
      C(p)/T(3) vs peaks in metallic and oxide glasses to elemental crystals by
      analyzing specific heat, phonon density of states, and elastic constant data. We
      observe no clear distinction in the peak temperature or amplitude between
      metallic glasses and crystals. Surprisingly, the peak is larger in single crystal
      Pd(40)Cu(40)P(20) than in glassy Pd(40)Cu(40)P(20).

PMID- 16803112
TI  - Banding in entangled polymer fluids under oscillatory shearing.
AB  - We report a flow phenomenon in entangled polymer solutions that has never been
      described in the literature. A large-amplitude oscillatory shear was imposed on
      the polymer sample at a frequency higher than the overall chain relaxation rate.
      The resulting chain orientation led to a new environment in which the initially
      well-entangled chains managed to disentangle inhomogeneously in space. A layer
      lacking chain entanglement developed to take the load of the imposed strain. As a
      result of this nonlinearity, the rest of the sample avoided significant
      deformation and its chain entanglement remained intact.

PMID- 16803113
TI  - Determination of interface atomic structure and its impact on spin transport
      using Z-contrast microscopy and density-functional theory.
AB  - We combine Z-contrast scanning transmission electron microscopy with density
      functional-theory calculations to determine the atomic structure of the interface
      in spin-polarized light-emitting diodes. A 44% increase in spin-injection
      efficiency occurs after a low-temperature anneal, which produces an ordered,
      coherent interface consisting of a single atomic plane of alternating Fe and As
      atoms. First-principles transport calculations indicate that the increase in spin
      injection efficiency is due to the abruptness and coherency of the annealed
      interface.

PMID- 16803114
TI  - New linear-parabolic rate equation for thermal oxidation of silicon.
AB  - We propose a new oxidation rate equation for silicon supposing only a diffusion
      of oxidizing species but not including any rate-limiting step by interfacial
      reaction. It is supposed that diffusivity is suppressed in a strained oxide
      region near SiO(2)/Si the interface. The expression of a parabolic constant in
      the new equation is the same as that of the Deal-Grove model, while a linear
      constant makes a clear distinction with that of the model. The estimated
      thickness using the new expression is close to 1 nm, which compares well with the
      thickness of the structural transition layers.

PMID- 16803115
TI  - Correlated hybridization in transition-metal complexes.
AB  - We apply local orbital basis density functional theory (using SIESTA) coupled
      with a mapping to the Anderson impurity model to estimate the Coulomb assisted or
      correlated hybridization between transition-metal orbitals and ligand orbitals
      for a number of molecular complexes. We find remarkably high values which can
      have several physical implications including (i) renormalization of effective
      single-band or multiband Hubbard model parameters for the cuprates and,
      potentially, elemental iron, and (ii) spin polarizing molecular transistors.

PMID- 16803116
TI  - Nitrogen vacancies as major point defects in gallium nitride.
AB  - We present results of ab initio calculations for vacancies and divacancies in
      GaN. Particular attention is paid to nitrogen vacancies and mixed Ga-N
      divacancies in negatively charged states, which in n-type GaN are found to be
      energetically comparable with gallium vacancies. We also demonstrate that the
      activation energy for self-diffusion over the nitrogen sublattice is lower than
      over the gallium one for all Fermi-level positions, which implies the nitrogen
      vacancies are major defects in samples annealed at high temperatures.
      Possibilities for direct observations of nitrogen vacancies through positron
      annihilation experiments are discussed.

PMID- 16803117
TI  - New Luttinger-liquid physics from photoemission on Li0.9M06O17.
AB  - Temperature dependent high resolution photoemission spectra of quasi-one
      dimensional Li(0.9)Mo(6)O(17)evince a strong renormalization of its Luttinger
      liquid density-of-states anomalous exponent. We trace this new effect to
      interacting charge neutral critical modes that emerge naturally from the two-band
      nature of the material. Li(0.9)Mo(6)O(17) is shown thereby to be a paradigm
      material that is capable of revealing new Luttinger physics.

PMID- 16803119
TI  - Dynamic response of one-dimensional interacting fermions.
AB  - We evaluate the dynamic structure factor S(q, omega) of interacting one
      dimensional spinless fermions with a nonlinear dispersion relation. The combined
      effect of the nonlinear dispersion and of the interactions leads to new universal
      features of S(q, omega). The sharp peak S(q, omega) approximately q(delta(omega 
      uq), characteristic for the Tomonaga-Luttinger model, broadens up; for a fixed
      becomes finite at arbitrarily large . The main spectral weight, however, is
      confined to a narrow frequency interval of the width deltaomega approximately
      q(2)/m. At the boundaries of this interval the structure factor exhibits power
      law singularities with exponents depending on the interaction strength and on the
      wave number q.

PMID- 16803118
TI  - Tunable anomalous Hall effect in a nonferromagnetic system.
AB  - We measure the low-field Hall resistivity of a magnetically doped two-dimensional
      electron gas as a function of temperature and electrically gated carrier density.
      Comparing these results with the carrier density extracted from Shubnikov-de Haas
      oscillations reveals an excess Hall resistivity that increases with decreasing
      temperature. This excess Hall resistivity qualitatively tracks the paramagnetic
      polarization of the sample, in analogy to the ferromagnetic anomalous Hall
      effect. The data are consistent with skew scattering of carriers by disorder near
      the crossover to localization.

PMID- 16803120
TI  - Magnetic domain formation in itinerant metamagnets.
AB  - We examine the effects of long-range dipolar forces on metamagnetic transitions
      and generalize the theory of Condon domains to the case of an itinerant electron
      system undergoing a first-order metamagnetic transition. We demonstrate that,
      within a finite range of the applied field, dipolar interactions induce a spatial
      modulation of the magnetization in the form of stripes or bubbles. Our findings
      are consistent with recent observations in the bilayer ruthenate Sr(3)Ru(2)O(7).

PMID- 16803121
TI  - Quantum-tunneling-induced Kondo effect in single molecular magnets.
AB  - We consider transport through a single-molecule magnet strongly coupled to
      metallic electrodes. We demonstrate that, for a half-integer spin of the
      molecule, electron and spin tunneling cooperate to produce both quantum tunneling
      of the magnetic moment and a Kondo effect in the linear conductance. The Kondo
      temperature depends sensitively on the ratio of the transverse and easy-axis
      anisotropies in a nonmonotonic way. The magnetic symmetry of the transverse
      anisotropy imposes a selection rule on the total spin for the occurrence of the
      Kondo effect which deviates from the usual even-odd alternation.

PMID- 16803122
TI  - Nonlinear 2D spin susceptibility in a finite magnetic field: spin-polarization
      dependence.
AB  - By theoretically calculating the interacting spin susceptibility of a two
      dimensional electron system in the presence of finite spin polarization, we show
      that the extensively employed technique of measuring the 2D spin susceptibility
      by linear extrapolation to a zero field from the finite-field experimental data
      is theoretically unjustified due to the strong nonlinear magnetic field
      dependence of the interacting susceptibility. Our work compellingly establishes
      that much of the prevailing interpretation of the 2D susceptibility measurements
      is incorrect, and, in general, the 2D interacting susceptibility cannot be
      extracted from the critical magnetic field for full spin polarization, as is
      routinely done experimentally.

PMID- 16803123
TI  - Crossover between monopole and multipole plasmon of Cs monolayers on Si(111)
      individually resolved in energy and momentum.
AB  - The evolution of the plasmon spectrum of the Si(111) (7 x 7)-Cs surface has been
      studied by energy loss spectroscopy individually resolved in energy and momentum
      during the transition from substrate to Cs overlayer metallization. The multipole
      plasmon is identified by an extremely narrow angular distribution of the
      inelastic electron scattering, unaccounted for by standard dipole scattering
      theory. A crossover between multipole and monopole surface plasmon is observed at
      finite surface wave vectors , depending on Cs coverage, and reveals a high
      sensitivity of the short-wavelength multipole components on surface morphology.

PMID- 16803124
TI  - Anisotropic states of two-dimensional electrons in high magnetic fields.
AB  - We study the collective states formed by two-dimensional electrons in Landau
      levels of index n > or = near half filling. By numerically solving the self
      consistent Hartree-Fock (HF) equations for a set of oblique two-dimensional
      lattices, we find that the stripe state is an anisotropic Wigner crystal (AWC),
      and determine its precise structure for varying values of the filling factor.
      Calculating the elastic energy, we find that the shear modulus of the AWC is
      small but finite (nonzero) within the HF approximation. This implies, in
      particular, that the long-wavelength magnetophonon mode in the stripe state
      vanishes q(3/2) like as in an ordinary Wigner crystal, and not like q(5/2) as was
      found in previous studies where the energy of shear deformations was neglected.

PMID- 16803125
TI  - Universal behavior of nearly free electron states in carbon nanotubes.
AB  - The nearly free electron state of a carbon nanotube drops rapidly in energy
      relative to the other conduction bands under alkali doping. A natural (and
      previously proposed) explanation for this rapid downshift is hybridization with
      the potassium states. However, we show that the downshift occurs even when the
      extra electrons are compensated by a uniform positive background, wherein there
      can be no hybridization, since there are no alkali atoms. Instead, the motion of
      the nearly free band arises from a universal electrostatic mechanism, which
      applies for any type of positive countercharge independent of tube diaf/meter and
      helicity. The nearly free electron state, being weakly bound to the tube wall, is
      extraordinarily labile and deforms onto the countercharge, whereas the remaining
      pi* conduction band states are held to the surface of the carbon sheet by the
      strong carbon potential.

PMID- 16803097
TI  - Measurement of the ratios of branching fractions and.
AB  - We report an observation of the decay B(O)(S) --> D(-)(s)pi(+) in pp collisions
      at radical S = 1.96 TeV using 115 pb(-1) of data collected by the CDF II detector
      at the Fermilab Tevatron. We observe 83 +/- 11(stat) B(O)(s) --> D(-)(s)pi(+)
      candidates, representing a large increase in statistics over previous
      measurements and the first observation of this decay at a pp collider. We present
      the first measurement of the relative branching fraction Beta(B(O)(s) --> D(
      )(s)pi(+))/Beta(B(0) --> D(-)(pi)(+)) = 1.32 +/- 0.18(stat) +/- 0.38(syst). We
      also measure Beta(B(+) --> D(0)pi(+))/Beta(B(0) -->D(-)pi(+)) = 1.97 +/-
      0.10(stat) +/- 0.21(syst), which is consistent with previous measurements.

PMID- 16803126
TI  - Ehrenfest time and the coherent backscattering off ballistic cavities.
AB  - If the Ehrenfest time tau(E) of a ballistic cavity is not negligible in
      comparison to its dwell time tau(D), the weak localization correction to the
      cavity's transmission is suppressed proportional to exp(-tau(E/tau(D). At the
      same time, quantum interference enhances the probability of reflection into the
      mode of incidence by a factor two. This "enhanced backscattering" does not depend
      on the Ehrenfest time. We show that, in addition to the diagonal enhanced
      backscattering, there are off-diagonal contributions to coherent backscattering
      that become relevant if tau(E) > or = tau(D).

PMID- 16803127
TI  - Spin quantum tunneling in single molecular magnets: fingerprints in transport
      spectroscopy of current and noise.
AB  - We demonstrate that transport spectroscopy of single molecular magnets shows
      signatures of quantum tunneling at low temperatures. We find current and noise
      oscillations as a function of bias voltage due to a weak violation of spin
      selection rules by quantum tunneling processes. The interplay with Boltzmann
      suppression factors leads to fake resonances with temperature-dependent position
      which do not correspond to any charge excitation energy. Furthermore, we find
      that quantum tunneling can completely suppress transport if the transverse
      anisotropy has a high symmetry.

PMID- 16803128
TI  - Interface energetics and level alignment at covalent metal-molecule junctions: pi
      conjugated thiols on gold.
AB  - The energetics at the interfaces between metal and monolayers of covalently bound
      organic molecules is studied theoretically. Despite the molecules under
      consideration displaying very different frontier orbital energies, the highest
      occupied molecular levels are found to be pinned at a constant energy offset with
      respect to the metal Fermi level. In contrast, the molecular properties strongly
      impact the metal work function. These interfacial phenomena are rationalized in
      terms of charge fluctuations and electrostatics at the atomic length scale as
      determined by first-principles calculations.

PMID- 16803130
TI  - Quantization of 2D hole gas in conductive hydrogenated diamond surfaces observed
      by electron field emission.
AB  - Discrete jumps are observed in the emitted current density (J) versus extraction
      electric field (E) curves in electron field emission measurements from a
      conductive, hydrogen-terminated air-exposed diamond surface. These jumps are well
      reproduced by computations based on the assumption that a 2D nanoscale quantum
      system with discrete energy levels exists in the diamond near-surface layer. The
      present results confirm the formation of well-defined quantum states of holes in
      the 2D surface layer present on hydrogenated air-exposed diamond surfaces.

PMID- 16803129
TI  - Photochemistry on thin metal films: probe of electron dynamics in metal
      semiconductor heterosystems.
AB  - The surface photochemistry of on ultrathin epitaxial Ag films on Si(100)
      substrates has been studied with the goal to employ it as a tool to unravel the
      electron dynamics in such films. An increase of the photodesorption cross section
      is observed--a factor of 5 for 266 nm light and 12 nm film thickness--when the
      film thickness is decreased, despite the fact that the optical absorbtivity
      decreases. The increased photodesorption cross section is interpreted to result
      from photon absorption in the Si substrate producing electrons at energies and
      parallel momenta which are not allowed in Ag. These electrons penetrate through
      the Ag film despite the gap in the surface projected band structure utilizing
      quantum resonances.

PMID- 16803132
TI  - Local electronic structure of near oxygen dopants: a window on the high-Tc
      pairing mechanism.
AB  - The cuprate material (Bi(2)Sr(2)CaCu(2)O-2212) is believed to be doped by a
      combination of cation switching and excess oxygen. The interstitial oxygen
      dopants are of particular interest because scanning tunneling microscopy (STM)
      experiments have shown that they are positively correlated with the local value
      of the superconducting gap, and calculations suggest that the fundamental
      attraction between electrons is modulated locally. In this work, we use density
      functional theory to try to ascertain which locations in the crystal are
      energetically most favorable for the O dopant atoms, and how the surrounding cage
      of atoms deforms. Our results provide support for the identification of STM
      resonances at -1 with dopant interstitial O atoms, and show how the local
      electronic structure is modified nearby.

PMID- 16803131
TI  - Magnetic order in the pseudogap phase of high-Tc superconductors.
AB  - One of the leading issues in high-T(c) superconductors is the origin of the
      pseudogap phase in underdoped cuprates. Using polarized elastic neutron
      diffraction, we identify a novel magnetic order in the YB(2)Cu(3)O(6+) system.
      The observed magnetic order preserves translational symmetry of the lattice as
      proposed for orbital moments in the circulating current theory of the pseudogap
      state. To date, it is the first direct evidence of a hidden order parameter
      characterizing the pseudogap phase in high-T(c) cuprates.

PMID- 16803133
TI  - Thickness dependence of the Josephson ground States of superconductor-ferromagnet
      superconductor junctions.
AB  - We report the first experimental observation of the two-node thickness dependence
      of the critical current in Josephson junctions with a ferromagnetic interlayer.
      Nodes of the critical current correspond to the transitions into the pi state and
      back into the conventional 0 state. From the experimental data the
      superconducting order parameter oscillation period and the pair decay length in
      the ferromagnet are extracted reliably. We develop a theoretical approach based
      on the Usadel equations taking into account the spin-flip scattering. Results of
      numerical calculations are in good agreement with experiments.

PMID- 16803134
TI  - Quasi-Kondo phenomenon due to the dynamical Jahn-Teller effect.
AB  - A mechanism of the nonmagnetic Kondo effect is proposed on the basis of a
      multiorbital Anderson model coupled with dynamical Jahn-Teller (JT) phonons. An
      electron system coupled dynamically with JT phonons has a vibronic ground state
      with double degeneracy due to clockwise and anticlockwise rotational modes with
      entropy of log2. When a temperature is lower than a characteristic energy to turn
      the rotational direction, the rotational degree of freedom is eventually
      suppressed and the corresponding entropy is released, leading to quasi-Kondo
      behavior. We discuss a simple relation between the "Kondo" temperature and the JT
      energy.

PMID- 16803135
TI  - Random-field spin models beyond 1 loop: a mechanism for decreasing the lower
      critical dimension.
AB  - The functional renormalization group for the random-field and random-anisotropy
      O(N) sigma models is studied to 2 loop. The ferromagnetic-disordered (F-D)
      transition fixed point is found to next order in d = 4 + epsilon for N > N(c)
      (N(c) = 2.834 740 8 for random field, N(c) = 9.441 21 for random anisotropy). For
      N < N(c) the lower critical dimension d = d(lc) plunges below d(lc) = 4: we find
      two fixed points, one describing the quasiordered phase, the other is novel and
      describes the F-D transition. d(lc) can be obtained in an (N(c)-N) expansion. The
      theory is also analyzed at large N and a glassy regime is found.

PMID- 16803136
TI  - Half-metallic ferromagnetism induced by dynamic electron correlations in VAs.
AB  - The electronic structure of the VAs compound in the zinc-blende structure is
      investigated using a combined density-functional and dynamical mean-field theory
      approach. Contrary to predictions of a ferromagnetic semiconducting ground state
      obtained by density-functional calculations, dynamical correlations induce a
      closing of the gap and produce a half-metallic ferromagnetic state. These results
      emphasize the importance of dynamic correlations in materials suitable for
      spintronics.

PMID- 16803137
TI  - Low-temperature solution of the Sherrington-Kirkpatrick model.
AB  - I propose a simple scaling ansatz for the full replica symmetry breaking solution
      of the Sherrington-Kirkpatrick model in the low energy sector. This solution is
      shown to become exact in the limit x --> 0, Bx --> infinity of the Parisi replica
      symmetry breaking scheme parameter . The distribution function of the frozen
      fields has been known to develop a linear gap at zero temperature. The scaling
      equations are integrated to find an exact numerical value for the slope of the
      gap thetaP(x,y)/delta|(y --> 0) = 0.301 046.... I also use the scaling solution
      to devise an inexpensive numerical procedure for computing finite time scale (x
      =1) quantities. The entropy, the zero field cooled susceptibility, and the local
      field distribution function are computed in the low-temperature limit with high
      precision, barely achievable by currently available methods.

PMID- 16803138
TI  - Spin-liquid correlations in the Nd-langasite anisotropic kagome antiferromagnet.
AB  - Dynamical magnetic correlations in the geometrically frustrated Nd(3)Ga(5)SiO(14)
      compound were probed by inelastic neutron scattering on a single crystal. A
      scattering signal with a ring shape distribution in reciprocal space and
      unprecedented dispersive features was discovered. Comparison with calculated
      static magnetic scattering from models of correlated spins suggests that the
      observed phase is a spin liquid inherent to an antiferromagnetic kagome-like
      lattice of anisotropic Nd moments.

PMID- 16803139
TI  - Evidence of two dimensionality in quasi-one-dimensional cobalt oxides.
AB  - The quasi-one-dimensional (Q1D) cobalt oxides A(N + 2)Co(n + 1)O(3n + 3) (A = Ca,
      Sr, and Ba, n = 1 - infinity) were investigated by muon-spin spectroscopy under
      applied pressures of up to 1.1 GPa. The relationship between the onset Neel
      temperature T(on)(N) and the interchain distance (d(ic)), which increases
      monotonically with n, is well fitted by the formula T(N)/T(N,0) = (1 -
      d(ic)/d(ic,o)(beta), here for T(on)(N) approximately 100 K for Ca(3)Co(2)O(6) (n
      = 1) and approximately 15 for BaCoCoO(3) (n = infinity at ambient P. The T(on)(N)
      - d(ic) curve also predicts a large dependence of Y(N) for the compounds with n >
      or = 5, i.e., in the vicinity of , while the compounds show only a very small
      effect. Indeed, our high-pressure mu(+) results show that of BaCoO(3) is enhanced
      by with a slope of 2.2 K(Gpa), whereas no detectable changes by P for both
      Ca(3)Co(2)O(6) and Sr(4)Co(3)O(9) (n = 2). This clearly confirms the role of the
      2D-antiferromagnetic interaction on T(on)(N) in the Q1D cobalt oxides.

PMID- 16803140
TI  - Influence of current on field-driven domain wall motion in permalloy nanowires
      from time resolved measurements of anisotropic magnetoresistance.
AB  - The motion of magnetic domain walls in permalloy nanowires is investigated by
      real-time resistance measurements. The domain wall velocity is measured as a
      function of the magnetic field in the presence of a current flowing through the
      nanowire. We show that the current can significantly increase or decrease the
      domain wall velocity, depending on its direction. These results are understood
      within a one-dimensional model of the domain wall dynamics which includes the
      spin transfer torque.

PMID- 16803141
TI  - Room-temperature magneto-optics of ferromagnetic transition-metal-doped ZnO thin
      films.
AB  - Magneto-optic studies of ZnO doped with transition metals Co, Mn, V, and Ti
      indicate a significant magnetic circular dichroism (MCD) at the ZnO band edge at
      room temperature, together with an associated dispersive Faraday rotation.
      Similar spectra occur for each dopant, which implies that the ferromagnetism is
      an intrinsic property of the bulk ZnO lattice. At 10 K, additional paramagnetic
      contributions to the MCD are observed, but above about 150 K, the magnitude of
      the MCD signal is dominated by the ferromagnetism and is almost temperature
      independent. The MCD at the ZnO band edge shows room temperature hysteretic
      behavior.

PMID- 16803143
TI  - Sequential recruitment and combinatorial assembling of multiprotein complexes in
      transcriptional activation.
AB  - In human cells, estrogenic signals induce cyclical association and dissociation
      of specific proteins with the DNA in order to activate transcription of estrogen
      responsive genes. These oscillations can be modeled by assuming a large number of
      sequential reactions represented by linear kinetics with random kinetic rates.
      Application of the model to experimental data predicts robust binding sequences
      in which proteins associate with the DNA at several different phases of the
      oscillation. Our methods circumvent the need to derive detailed kinetic graphs,
      and are applicable to other oscillatory biological processes involving a large
      number of sequential steps.

PMID- 16803142
TI  - Rearrangement of lipid ordered phases upon protein adsorption due to multiple
      site binding.
AB  - This study involves the interactions of proteins with Langmuir monolayers of a
      metal-chelating lipid, where adsorption is driven by a strong specific
      interaction between histidines on the proteins and divalent metal ions loaded
      into the lipid headgroups. A comparison of the structural rearrangement of the
      lipid film upon adsorption of myoglobin and a synthetic peptide, each of which
      have multiple histidines, with that upon the adsorption of lysozyme, which has
      only one histidine, suggests that the lipid rearrangement in the former case is
      due to the multiplicity of binding sites. The kinetics and manner of
      rearrangement change with the binding energy and film pressure.

PMID- 16803144
TI  - Glasslike structure of globular proteins and the boson peak.
AB  - Vibrational spectra of proteins and topologically disordered solids display a
      common anomaly at low frequencies, known as boson peak. We show that such feature
      in globular proteins can be deciphered in terms of an energy landscape picture,
      as it is for glassy systems. Exploiting the tools of Euclidean random matrix
      theory, we clarify the physical origin of such anomaly in terms of a mechanical
      instability of the system. As a natural explanation, we argue that such
      instability is relevant for proteins in order for their molecular functions to be
      optimally rooted in their structures.

PMID- 16803145
TI  - Irreversible shear-activated aggregation in non-Brownian suspensions.
AB  - We have studied the effect of shear on the stability of suspensions made of non
      Brownian solid particles. We demonstrate the existence of an irreversible
      transition where the solid particles aggregate at remarkably low volume fractions
      (phi approximately 0.1). This shear-induced aggregation is dramatic and exhibits
      a very sudden change in the viscosity, which increases sharply after a shear
      dependent induction time. We show that this induction time is related
      exponentially to the shear rate, reflecting the importance of the hydrodynamic
      forces in reducing the repulsive energy barrier that prevents the particles from
      aggregating.

PMID- 16803146
TI  - Spin transition in magnesiowustite in earth's lower mantle.
AB  - Iron in the major lower mantle (LM) minerals undergoes a high spin (HS) to low
      spin (LS) transition at relevant pressures (23-135 GPa). Previous failures of
      standard first principles approaches to describe this phenomenon have hindered
      its investigation and the clarification of important consequences. Using a
      rotationally invariant formulation of LDA + U we report a successful study of
      this transition in low solute concentration magnesiowustite, (Mg(1-x)Fe(x)(O), (x
      < 0.2) the second most abundant LM phase. We show that the HS-LS transition goes
      through an insulating (semiconducting) intermediate mixed spins (MS) state
      without discontinuous changes in properties, as seen experimentally. We show that
      the HS state crosses over smoothly to the LS state passing through an insulating
      MS state where properties change continuously, as seen experimentally.

PMID- 16803147
TI  - Comment on "surprises in threshold antikaon-nucleon physics".

PMID- 16803149
TI  - Comment on "finite element mapping for spring network representations of the
      mechanics of solids".

PMID- 16803151
TI  - Comment on "fraction of boroxol rings in vitreous boron oxide from a first
      principles analysis of Raman and NMR spectra".

PMID- 16803153
TI  - Comment on "trapping single molecules by dielectrophoresis".

PMID- 16803155
TI  - Identification and distance measures of measurement apparatus.
AB  - We propose simple schemes that can perfectly identify projective measurement
      apparatuses secretly chosen from a finite set. Entanglement is used in these
      schemes both to make possible the perfect identification and to improve the
      efficiency significantly. Based on these results, a brief discussion on the
      problem of how to appropriately define distance measures of measurements is also
      provided.

PMID- 16803156
TI  - Detectability of dissipative motion in quantum vacuum via superradiance.
AB  - We propose an experiment for generating and detecting vacuum-induced dissipative
      motion. A high frequency mechanical resonator driven in resonance is expected to
      dissipate mechanical energy in quantum vacuum via photon emission. The photons
      are stored in a high quality electromagnetic cavity and detected through their
      interaction with ultracold alkali-metal atoms prepared in an inverted population
      of hyperfine states. Superradiant amplification of the generated photons results
      in a detectable radio-frequency signal temporally distinguishable from the
      expected background.

PMID- 16803157
TI  - Universal measurement of quantum correlations of radiation.
AB  - A measurement technique is proposed which, in principle, allows one to observe
      the general space-time correlation properties of a quantized radiation field. Our
      method, called balanced homodyne correlation measurement, unifies the advantages
      of balanced homodyne detection with those of homodyne correlation measurements.

PMID- 16803158
TI  - Signatures of quantum behavior in single-qubit weak measurements.
AB  - With the recent surge of interest in quantum computation, it has become very
      important to develop clear experimental tests for "quantum behavior" in a system.
      This issue has been addressed in the past in the form of the inequalities due to
      Bell and those due to Leggett and Garg. These inequalities concern the results of
      ideal projective measurements, however, which are experimentally difficult to
      perform in many proposed qubit designs, especially in many solid-state qubit
      systems. Here, we show that weak continuous measurements, which are often
      practical to implement experimentally, can yield particularly clear signatures of
      quantum coherence, both in the measured correlation functions and in the measured
      power spectrum.

PMID- 16803159
TI  - Phase separation of a fast rotating boson-fermion mixture in the lowest-Landau
      level regime.
AB  - By minimizing the coupled mean-field energy functionals, we investigate the
      ground-state properties of a rotating atomic boson-fermion mixture in a two
      dimensional parabolic trap. At high angular frequencies in the mean-field lowest
      Landau-level regime, quantized vortices enter the bosonic condensate, and a
      finite number of degenerate fermions form the maximum-density-droplet state. As
      the boson-fermion coupling constant increases, the maximum density droplet
      develops into a lower-density state associated with the phase separation,
      revealing characteristics of a Landau-level structure.

PMID- 16803160
TI  - Experimental test of two-way quantum key distribution in the presence of
      controlled noise.
AB  - We describe the experimental test of a quantum key distribution performed with a
      two-way protocol without using entanglement. An individual incoherent
      eavesdropping is simulated and induces a variable amount of noise on the
      communication channel. This allows a direct verification of the agreement between
      theory and practice.

PMID- 16803161
TI  - Limits on Lorentz violation from synchrotron and inverse Compton sources.
AB  - We derive new bounds on Lorentz violations in the electron sector from existing
      data on high-energy astrophysical sources. Synchrotron and inverse Compton data
      give precisely complementary constraints. The best bound on a specific
      combination of electron Lorentz-violating coefficients is at the 6 x 10(-20)
      level, and independent bounds are available for all the Lorentz-violating c
      coefficients at the 2 x 10(-14)level or better. This represents an improvement in
      some bounds by 14 orders of magnitude.

PMID- 16803162
TI  - A new mechanism for gravitational-wave emission in core-collapse supernovae.
AB  - We present a new theory for the gravitational-wave signatures of core-collapse
      supernovae. Previous studies identified axisymmetric rotating core collapse, core
      bounce, postbounce convection, and anisotropic neutrino emission as the primary
      processes and phases for the radiation of gravitational waves. Our results, which
      are based on axisymmetric Newtonian supernova simulations, indicate that the
      dominant emission process of gravitational waves in core-collapse supernovae may
      be the oscillations of the protoneutron star core. The oscillations are
      predominantly of mode character, are excited hundreds of milliseconds after
      bounce, and typically last for several hundred milliseconds. Our results suggest
      that even nonrotating core-collapse supernovae should be visible to current LIGO
      class detectors throughout the Galaxy, and depending on progenitor structure,
      possibly out to megaparsec distances.

PMID- 16803163
TI  - Hadronic spectra and light-front wave functions in holographic QCD.
AB  - We show how the string amplitude phi(z) defined on the fifth dimension in AdS5
      space can be precisely mapped to the light-front wave functions of hadrons in
      physical space-time. We find an exact correspondence between the holographic
      variable z and an impact variable zeta, which represents the measure of
      transverse separation of the constituents within the hadrons. In addition, we
      derive effective four dimensional Schrodinger equations for the bound states of
      massless quarks and gluons which exactly reproduce the anti-de Sitter conformal
      field theory results and give a realistic description of the light-quark meson
      and baryon spectrum as well as the form factors for space-like Q2. Only one
      parameter which sets the mass scale, lambda(QCD), is introduced.

PMID- 16803164
TI  - Gravitational instantons from gauge theory.
AB  - A gauge theory can be formulated on a noncommutative (NC) spacetime. This NC
      gauge theory has anequivalent dual description through the so-called Seiberg
      Witten (SW) map in terms of an ordinary gauge theory on a commutative spacetime.
      We show that all NC U(1) instantons of Nekrasov-Schwarz type are mapped to
      asymptotically locally Euclidean (ALE) gravitational instantons by the exact SW
      map and thatthe NC gauge theory of U(1) instantons is equivalent to the theory of
      hyper-Kahler geometries. It implies the remarkable consequence that ALE
      gravitational instantons can emerge from local condensates of purely NC photons.

PMID- 16803169
TI  - Elliptic flow of thermal photons in relativistic nuclear collisions.
AB  - We predict the transverse momentum (p(T)) dependence of elliptic flow of thermal
      photons for Au + Au collisions at the BNL Relativistic Heavy Ion Collider. We
      model the system hydrodynamically, with a thermalized quark-gluon plasma at early
      times followed by hadronization and decoupling. Photons are emitted throughout
      the expansion history. Contrary to hadron elliptic flow, which increases
      monotonically with p(T), the elliptic flow nu2(p(T)) of thermal photons is
      predicted to first rise and then fall again. Photon elliptic flow at high p(T)
      reflects the quark momentum anisotropy at early times when it is small, while at
      low p(T) it mirrors the large pion momentum anisotropy during the late hadronic
      emission stage. An interesting structure is predicted at intermediate p(T)
      approximately 0.4 GeV/c, where photon elliptic flow reflects the momenta and the
      (compared to pions) reduced nu2 of heavy vector mesons in the late hadronic
      phase.

PMID- 16803170
TI  - High-order harmonic generation from ions in a capillary discharge.
AB  - We demonstrate a significant extension of the high-order harmonic cutoff by using
      a fully-ionized capillary discharge plasma as the generation medium. The
      preionized plasma dramatically reduces ionization-induced defocusing and energy
      loss of the driving laser due to ionization. This allows for significantly higher
      photon energies, up to 150 eV, to be generated from xenon ions, compared with the
      70 eV observed previously. We also demonstrate enhancement of the harmonic flux
      of nearly 2 orders of magnitude at photon energies around 90 eV when the
      capillary discharge is used to ionize xenon, compared with harmonic generation in
      a hollow waveguide. The use of a plasma as a medium for high-order harmonic
      generation shows great promise for extending efficient harmonic generation to
      much shorter wavelengths using ions.

PMID- 16803171
TI  - Narrow line photoassociation in an optical lattice.
AB  - With ultracold 88Sr in a 1D magic wavelength optical lattice, we performed narrow
      line photoassociation spectroscopy near the 1S0 - 3P1 intercombination
      transition. Nine least-bound vibrational molecular levels associated with the
      long-range 0u and 1u potential energy surfaces were measured and identified. A
      simple theoretical model accurately describes the level positions and treats the
      effects of the lattice confinement on the line shapes. The measured resonance
      strengths show that optical tuning of the ground state scattering length should
      be possible without significant atom loss.

PMID- 16803172
TI  - Nonlinear interferometry via Fock-state projection.
AB  - We use a photon-number-resolving detector to monitor the photon-number
      distribution of the output of an interferometer, as a function of phase delay. As
      inputs we use coherent states with mean photon number up to seven. The
      postselection of a specific Fock (photon-number) state effectively induces high
      order optical nonlinearities. Following a scheme by Bentley and Boyd [Opt.
      Express 12, 5735 (2004).10.1364/OPEX.12.005735], we explore this effect to
      demonstrate interference patterns a factor of 5 smaller than the Rayleigh limit.

PMID- 16803173
TI  - Measurement of pressure and density inside a single sonoluminescing bubble.
AB  - The average pressure inside a sonoluminescing bubble in sulfuric acid has been
      determined by two independent techniques: (1) plasma diagnostics applied to Ar
      atom emission lines, and (2) light scattering measurements of bubble radius vs
      time. For dimly luminescing bubbles, both methods yield intracavity pressures
      approximately 1500 bar. Upon stronger acoustic driving of the bubble, the
      sonoluminescence intensity increases 10,000-fold, spectral lines are no longer
      resolved, and radius vs time measurements yield internal pressures > 3700 bar.
      Implications for a hot inner core are discussed.

PMID- 16803174
TI  - Homogenization of two-dimensional clusters of rigid rods in air.
AB  - The scattering of sound waves by circular-shaped clusters consisting of two
      dimensional distributions of rigid cylinders in air is studied in the low
      frequency limit (homogenization) both theoretically and experimentally.
      Analytical formulas for the effective density and sound speed are obtained in the
      framework of multiple scattering. Here, an experimental demonstration is reported
      in which a cluster of wooden rods acoustically behaves as a cylinder of argon
      gas. Moreover, evidence is presented indicating the validity of the
      homogenization in this cluster at frequencies lower than 3 kHz, which corresponds
      to a wavelength that is only 4 times the parameter of the embedded lattice and is
      a quarter of the cluster's diameter.

PMID- 16803175
TI  - Momentum conserving model with anomalous thermal conductivity in low dimensional
      systems.
AB  - Anomalous large thermal conductivity has been observed numerically and
      experimentally in one- and two-dimensional systems. There is an open debate about
      the role of conservation of momentum. We introduce a model whose thermal
      conductivity diverges in dimensions 1 and 2 if momentum is conserved, while it
      remains finite in dimension d > or = 3. We consider a system of harmonic
      oscillators perturbed by a nonlinear stochastic dynamics conserving momentum and
      energy. We compute explicitly the time correlation function of the energy current
      C(J)(t), and we find that it behaves, for large time, like t(-d/2) in the
      unpinned cases, and like t(-d/2-1) when an on-site harmonic potential is present.
      This result clarifies the role of conservation of momentum in the anomalous
      thermal conductivity in low dimensions.

PMID- 16803176
TI  - Direct numerical simulation of downshift and inverse cascade for water wave
      turbulence.
AB  - By means of direct numerical simulations (DNS) based on the integrodifferential
      Zakharov equation, we study the long-term evolution of nonlinear random water
      wave fields. For the first time, formation of powerlike Kolmogorov-type spectra
      corresponding to weak-turbulent inverse cascade is demonstrated by DNS, and the
      evolution in time of the resulting spectra is quantitatively investigated. The
      predictions of the statistical theory for water waves, both qualitative
      (formation of the direct and inverse cascades, self-similar behavior) and
      quantitative (the spectra exponents, specific shape of self-similar functions,
      the rate of time evolution) are found to be in good agreement with the DNS
      results, except for the initial part of the evolution, where the established
      statistical theory is not applicable yet and the evolution has a much faster time
      scale.

PMID- 16803177
TI  - Cluster size distribution and scaling for spherical particles and red blood cells
      in pressure-driven flows at small Reynolds number.
AB  - The clustering characteristic of purely hydrodynamically interacting particles
      suspended in pressure-driven flow in a circular cylinder is studied using direct
      numerical simulation based on the solution of the lattice-Boltzmann equation. We
      find a universal scaling relation for the cluster size distribution in the
      subcritical regime for all of the cases considered in this study. This scaling
      relation is independent of particle shape and concentration.

PMID- 16803168
TI  - Common suppression pattern of eta and pi0 mesons at high transverse momentum in
      Au + Au collisions at square root S(NN) = 200 GeV.
AB  - Inclusive transverse momentum spectra of eta mesons have been measured within
      p(T) = 2-10 GeV/c at midrapidity by the PHENIX experiment in Au + Au collisions
      at square root S(NN) = 200 GeV. In central Au+Au the eta yields are significantly
      suppressed compared to peripheral Au + Au, d + Au, and p + p yields scaled by the
      corresponding number of nucleon-nucleon collisions. The magnitude, centrality,
      and p(T) dependence of the suppression is common, within errors, for eta and pi0.
      The ratio of eta to pi0 spectra at high p(T) amounts to 0.40 < R(eta/pi)0 < 0.48
      for the three systems, in agreement with the world average measured in hadronic
      and nuclear reactions and, at large scaled momentum, in e+e- collisions.

PMID- 16803178
TI  - Influence of turbulence on the dynamo threshold.
AB  - We use direct and stochastic numerical simulations of the magnetohydrodynamic
      equations to explore the influence of turbulence on the dynamo threshold. In the
      spirit of the Kraichnan-Kazantsev model, we model the turbulence by a noise, with
      given amplitude, injection scale, and correlation time. The addition of a
      stochastic noise to the mean velocity significantly alters the dynamo threshold
      and increases it for any noise at large scale. For small-scale noise, the result
      depends on its correlation time and on the magnetic Prandtl number.

PMID- 16803179
TI  - Collisionless heating in capacitive discharges enhanced by dual-frequency
      excitation.
AB  - We discuss collisionless electron heating in capacitive discharges excited by a
      combination of two disparate frequencies. By developing an analytical model, we
      find, contrary to expectation, that the net heating in this case is much larger
      than the sum of the effects occurring when the two frequencies act separately.
      This prediction is substantiated by kinetic simulations, which are also in
      excellent general quantitative agreement with the model for discharge parameters
      that are typical of recent experiments.

PMID- 16803180
TI  - Probing "cosmological" defects in superfluid 3He-B with a vibrating-wire
      resonator.
AB  - We report on the observation of an anomalously high damping measured by a
      vibrating-wire resonator (VWR) immersed into superfluid at ultralow temperatures.
      The observed dissipation is orders of magnitude above that corresponding to
      friction with the dilute normal fraction and superfluid vortices. A clear pinning
      behavior is also observed, as well as a strong magnetic field dependence. Our
      analysis points to the interaction of the VWR with a planar topological defect,
      analogue to cosmological vacua defects, as proposed by Salomaa and Volovik.

PMID- 16803181
TI  - Grain-boundary physics in polycrystalline CuInSe2 revisited: experiment and
      theory.
AB  - Current studies have attributed the remarkable performance of polycrystalline
      CuInSe2 (CIS) to anomalous grain-boundary (GB) physics in CIS. The recent theory
      predicts that GBs in CIS are hole barriers, which prevent GB electrons from
      recombining. We examine the atomic structure and chemical composition of (112)
      GBs in Cu(In,Ga)Se2 (CIGS) using high-resolution Z-contrast imaging and nanoprobe
      x-ray energy-dispersive spectroscopy. We show that the theoretically predicted Cu
      vacancy rows are not observed in (112) GBs in CIGS. Our first-principles modeling
      further reveals that the (112) GBs in CIS do not act as hole barriers. Our
      results suggest that the superior performance of polycrystalline CIS should not
      be explained solely by the GB behaviors.

PMID- 16803182
TI  - Density of vibrational states of a hyperquenched glass.
AB  - The vibrational density of states of a hyperquenched and an annealed glass has
      been measured using nuclear inelastic scattering. The hyperquenched sample shows
      a higher number of vibrational states in the low-energy region with respect to
      the annealed glass. It reveals, however, lower density and sound velocity and,
      therefore, smaller Debye energy. After rescaling the energy axes in Debye energy
      units and area renormalization, the density of states of both samples becomes
      identical. Thus, the effect of quenching is described by the transformation of
      the continuous medium.

PMID- 16803183
TI  - One-dimensional fluctuating nanodomains in the charge-transfer molecular system
      TTF-CA and their first-order crystallization.
AB  - We report on the direct observation by x-ray diffuse scattering measurements of
      thermally induced one-dimensional nanoscale ordered fluctuations in the mixed
      stack charge-transfer molecular system tetrathiafulvalene-p chloranil (TTF-CA),
      the prototype for the neutral-ionic phase transition. The unusual physical
      properties of this compound are considered to be driven by such one-dimensional
      excitations. The results are discussed in relation to previous experimental and
      theoretical experiments both at thermal equilibrium and under light irradiation.

PMID- 16803184
TI  - First-principles study of the diffusion of hydrogen in ZnO.
AB  - Zinc oxide, a wide-gap semiconductor, typically exhibits n-type conductivity even
      when nominally undoped. The nature of the donor is contentious, but hydrogen is a
      prime candidate. We present ab initio calculations of the migration barrier for
      H, yielding a barrier of less than approximately 0.5 eV. This indicates isolated
      hydrogen is mobile at low temperature and that thermally stable H-related donors
      must logically be trapped at other defects. We argue this is also true for other
      oxides where H is a shallow donor.

PMID- 16803185
TI  - Magnetically induced phonon anisotropy in ZnCr2O4 from first principles.
AB  - We have studied the influence of magnetic order on the optical phonons of the
      geometrically frustrated spinel ZnCr2O4 within density-functional theory. By
      mapping local spin density approximation plus Hubbard U (LSDA + U) phonon
      calculations onto a Heisenberg-like model, we developed a method to calculate
      exchange derivatives and subsequently the spin-phonon coupling parameter from
      first principles.

PMID- 16803186
TI  - Full recovery of electron damage in glass at ambient temperatures.
AB  - An unusually complete recovery of extensive electron-beam-induced damage in a
      thin film of a CaO-Al2O3-SiO2 glass was discovered. Nanoscale measurements show
      that the Ca ions migrate about 10 nm away during irradiation and return during
      recovery. Oxygen atoms are trapped largely as molecular oxygen and do not
      migrate. Electron energy loss measurements demonstrate that the glass returns
      completely to the original compositional and structural state thus indicating
      that the glass is in a deep thermodynamic energy minimum.

PMID- 16803187
TI  - Controlling density fluctuations in wall-bounded dissipative particle dynamics
      systems.
AB  - Dissipative Particle Dynamics (DPD) simulations of wall-bounded flows exhibit
      density fluctuations that depend strongly on the no-slip boundary condition and
      increase with the level of coarse graining. We develop an adaptive model for wall
      particle interactions that eliminates such oscillations and can target prescribed
      density profiles. Comparisons are made with ideal no-slip boundary conditions and
      molecular dynamics simulations. The new model is general and can be used in other
      coarse-grained particle methods.

PMID- 16803166
TI  - Measurement of bottom-quark hadron masses in exclusive J/psi decays with the CDF
      detector.
AB  - We measure the masses of b hadrons in exclusively reconstructed final states
      containing a J/psi --> mu-mu+ decay using 220 pb(-1) of data collected by the CDF
      II experiment. We find: m(B+) = 5279.10 +/- 0.41(stat.) +/- 0.36(sys.) MeV/c2,
      m(B0) = 5279.63 +/- 0.53(stat.) +/- 0.33(sys.) MeV/c2, m(B(s)0) = 5366.01 +/-
      0.73(stat.) +/- 0.33(sys.) MeV/c2, m(lambda(b)0) = 5619.7 +/- 1.2(stat.) +/-
      1.2(sys.) MeV/c2. m(B+) - m(B0) = -0.53 +/- 0.67(stat.) +/- 0.14(sys.) MeV/c2,
      m(B(s)0) - m(B0) = 86.38 +/- 0.90(stat.) +/- 0.06(sys.) MeV/c2, m(lambda(b)0) -
      m(B0) = 339.2 +/- 1.4(stat.) +/- 0.1(sys.) MeV/c2. The measurements of the B(s)0,
      lambda(b)0 mass, m(B(s)0) - m(B0) and m(lambda(b)0) - m(B0) mass difference are
      of better precision than the current world averages.

PMID- 16803188
TI  - Gas enrichment at liquid-wall interfaces.
AB  - Molecular dynamics simulations of Lennard-Jones systems are performed to study
      the effects of dissolved gas on liquid-wall and liquid-gas interfaces. Gas
      enrichment at walls, which for hydrophobic walls can exceed more than 2 orders of
      magnitude when compared to the gas density in the bulk liquid, is observed. As a
      consequence, the liquid structure close to the wall is considerably modified,
      leading to an enhanced wall slip. At liquid-gas interfaces gas enrichment which
      reduces the surface tension is found.

PMID- 16803165
TI  - Direct search for Dirac magnetic monopoles in pp collisions at square root s =
      1.96 TeV.
AB  - We search for pair-produced Dirac magnetic monopoles in 35.7 pb(-1) of proton
      antiproton collisions at square root s = 1.96 TeV with the Collider Detector at
      Fermilab (CDF). We find no monopole candidates corresponding to a 95% confidence
      level cross-section limit sigma < 0.2 pb for a monopole with mass between 200 and
      700 GeV/c2. Assuming a Drell-Yan pair-production mechanism, we set a mass limit m
      > 360 GeV/c2.

PMID- 16803189
TI  - Crystal bridge formation marks the transition to rigidity in a thin lubrication
      film.
AB  - We report that the rheological transition in a thin lubrication film of dodecane
      from bulk to high viscosity states as the thickness is decreased is the result of
      a novel structural transition. Using nonequilibrium molecular dynamics
      simulations we find that the initial increase in viscosity as the film thins is
      due to the formation of isolated crystalline bridges between the surfaces. As the
      thickness decreases further, these bridges increase in number and organize
      themselves into a tetratic order in the plane of the surface. We show that this
      ordered state melts at a temperature of 350 K.

PMID- 16803167
TI  - Measurement of the tt production cross section in pp collisions at square root s
      = 1.96 TeV using missing E(T) + jets events with secondary vertex b tagging.
AB  - We present a measurement of the tt production cross section in pp collisions at
      square root s = 1.96 TeV which uses events with an inclusive signature of
      significant missing transverse energy and jets. This is the first measurement
      which makes no explicit lepton identification requirements, so that sensitivity
      to W --> tau nu decays is maintained. Heavy flavor jets from top quark decay are
      identified with a secondary vertex tagging algorithm. From 311 pb(-1) of data
      collected by the Collider Detector at Fermilab, we measure a production cross
      section of 5.8 +/- 1.2(stat)(-0.7)(+0.9)(syst) pb for a top quark mass of 178
      GeV/c2, in agreement with previous determinations and standard model predictions.

PMID- 16803190
TI  - Nonlocal magnetic field-tuned quantum criticality in cubic CeIn(3-x)Sn(x) (x =
      0.25).
AB  - We show that antiferromagnetism in lightly (approximately 8%) Sn-doped CeIn3
      terminates at a critical field mu0H(c) = 42 +/- 2 T. Electrical transport and
      thermodynamic measurements reveal the effective mass m* not to diverge,
      suggesting that cubic CeIn3 is representative of a critical spin-density wave
      (SDW) scenario, unlike the local quantum critical points reported in anisotropic
      systems such as CeCu(6-x)Au(x) and YbRh2Si(2-x)Ge(x). The existence of a maximum
      in m* at a lower field mu0H(x) = 30 +/- 1 T may be interpreted as a field-induced
      crossover from local moment to SDW behavior as the Neel temperature falls below
      the Fermi temperature.

PMID- 16803191
TI  - Symmetry and stability of plutonium: the influence of electronic structure.
AB  - Using first-principles density-functional theory, we calculate the bond strengths
      between the 12 nearest neighbors in delta plutonium for both pure Pu and a Pu-3.7
      at. % Ga alloy. Our results for pure Pu reveal a structure with the monoclinic
      space group Cm rather than face-centered cubic Fm3m, showing that the anomalously
      large anisotropy of delta plutonium is a consequence of greatly varying bond
      strengths between the 12 nearest neighbors. Further results for a Pu-3.7 at. % Ga
      alloy show that the nearest-neighbor bond strengths around a Ga atom are more
      uniform. Hence, our calculations address (i) why the ground state of Pu is
      monoclinic, (ii) why distortions of the delta phase are viable, with considerable
      implications for the behavior of the material as it ages due to anisotropic
      response to self-irradiation, and (iii) why Ga stabilizes face-centered cubic
      delta-Pu.

PMID- 16803192
TI  - Electron transport through single Mn12 molecular magnets.
AB  - We report transport measurements through a single-molecule magnet, the Mn12
      derivative [Mn12O12(O2C-C6H4-SAc)16(H2O)4], in a single-molecule transistor
      geometry. Thiol groups connect the molecule to gold electrodes that are
      fabricated by electromigration. Striking observations are regions of complete
      current suppression and excitations of negative differential conductance on the
      energy scale of the anisotropy barrier of the molecule. Transport calculations,
      taking into account the high-spin ground state and magnetic excitations of the
      molecule, reveal a blocking mechanism of the current involving nondegenerate spin
      multiplets.

PMID- 16803193
TI  - Asymmetry of nonlinear transport and electron interactions in quantum dots.
AB  - The symmetry properties of transport beyond the linear regime in chaotic quantum
      dots are investigated experimentally. A component of differential conductance
      that is antisymmetric in both applied source-drain bias V and magnetic field B,
      absent in linear transport, is found to exhibit mesoscopic fluctuations around a
      zero average. Typical values of this component allow a measurement of the
      electron interaction strength.

PMID- 16803194
TI  - Size effects under a strong magnetic field: Hall effect induced by electron
      surface scattering on thin gold films deposited onto mica substrates under high
      vacuum.
AB  - We report measurements of the Hall effect performed on 4 gold films evaporated
      onto mica substrates where the signal arises primarily from electron-surface
      scattering. The measurements were performed at low temperatures T (4 K < or = T <
      or = 50 K) under high magnetic field strengths B (1.5 T < or = B < or = 9 T),
      with B oriented perpendicular to the films.

PMID- 16803195
TI  - Shot noise in semiclassical chaotic cavities.
AB  - We construct a trajectory-based semiclassical theory of shot noise in clean
      chaotic cavities. In the universal regime of vanishing Ehrenfest time tau(E), we
      reproduce the random matrix theory result and show that the Fano factor is
      exponentially suppressed as tau(E) increases. We demonstrate how our theory
      preserves the unitarity of the scattering matrix even in the regime of finite
      tau(E). We discuss the range of validity of our semiclassical approach and point
      out subtleties relevant to the recent semiclassical treatment of shot noise in
      the universal regime by Braun et al. (cond-mat/0511292).

PMID- 16803196
TI  - Novel commensurability effects in superconducting films with antidot arrays.
AB  - Vortex configurations in superconducting films with regular arrays of antidots
      (holes) are calculated within the nonlinear Ginzburg-Landau theory. In addition
      to the well-established matching phenomena, we predict (i) the nucleation of
      giant-vortex states between the antidots, (ii) the combination of giant- and
      multivortices at rational matching fields, and (iii) for particular values of the
      vorticity, symmetry imposed creation of vortex-antivortex configurations.

PMID- 16803197
TI  - Electronic structure of strongly correlated d-wave superconductors.
AB  - We study the electronic structure of a strongly correlated d-wave superconducting
      state. Combining a renormalized mean field theory with direct calculation of
      matrix elements, we obtain explicit analytical results for the nodal Fermi
      velocity upsilon(F), the Fermi wave vector k(F), and the momentum distribution
      n(k) as a function of hole doping in a Gutzwiller projected d-wave
      superconductor. We calculate the energy dispersion E(k) and spectral weight of
      the Gutzwiller-Bogoliubov quasiparticles and find that the spectral weight
      associated with the quasiparticle excitation at the antinodal point shows a
      nonmonotonic behavior as a function of doping. Results are compared to angle
      resolved photoemission spectroscopy of the high-temperature superconductors.

PMID- 16803198
TI  - Electron transport in single-wall carbon nanotube weak links in the Fabry-Perot
      regime.
AB  - We fabricated reproducible high transparency superconducting contacts consisting
      of superconducting Ti/Al/Ti trilayers to gated single-wall carbon nanotubes. The
      reported semiconducting single-wall carbon nanotubes have normal state
      differential conductance up to 3e2/h and exhibit clear Fabry-Perot interference
      patterns in the bias spectroscopy plot. We observed subharmonic gap structure in
      the differential conductance and a distinct peak in the conductance at zero bias,
      which is interpreted as a manifestation of the supercurrent. The gate dependence
      of this supercurrent as well as the excess current are examined and compared to
      the coherent theory of superconducting quantum point contacts with good
      agreement.

PMID- 16803199
TI  - Quantum criticality and percolation in dimer-diluted two-dimensional
      antiferromagnets.
AB  - The S = 1/2 Heisenberg model is considered on bilayer and single-layer square
      lattices with couplings J1, J2, with each spin belonging to one J2-coupled dimer.
      A transition from a Neel to disordered ground state occurs at a critical value of
      g = J2/J1. The systems are here studied at their dimer-dilution percolation
      points p*. The multicritical point (g*,p*) previously found for the bilayer is
      not reproduced for the single layer. Instead, there is a line of critical points
      (g < g*, p*) with continuously varying exponents. The uniform magnetic
      susceptibility diverges as T(-alpha) with alpha element of [1/2,1]. This unusual
      behavior is attributed to an effective free-moment density approximately T(1
      alpha). The susceptibility of the bilayer is not divergent but exhibits
      remarkably robust quantum-critical scaling.

PMID- 16803200
TI  - Theory of the helical spin crystal: a candidate for the partially ordered state
      of MnSi.
AB  - MnSi is an itinerant magnet which at low temperatures develops a helical spin
      density wave. Under pressure it undergoes a transition into an unusual partially
      ordered state whose nature is debated. Here we propose that the helical spin
      crystal (the magnetic analog of a solid) is a useful starting point to understand
      partial order in MnSi. We consider different helical spin crystals and determine
      conditions under which they may be energetically favored. The most promising
      candidate has bcc structure and is reminiscent of the blue phase of liquid
      crystals in that it has line nodes of magnetization protected by symmetry. We
      introduce a Landau theory to study the properties of these states, in particular,
      the effect of crystal anisotropy, magnetic field, and disorder. These results
      compare favorably with existing data on MnSi from neutron scattering and magnetic
      field studies. Future experiments to test this scenario are also proposed.

PMID- 16803201
TI  - Enhanced magnetoresistance induced by spin transfer torque in granular films with
      a magnetic field.
AB  - Spin-transfer torques (STT) provide a mechanism to alter the magnetic
      configurations of magnetic heterostructures, a result previously only achieved by
      an external magnetic field. In granular solids, we demonstrate a new form of STT
      effect that can be exploited to induce a large spin disorder when combined with a
      large magnetic field. We have obtained a very large magnetoresistance effect in
      excess of 400% at 4.2 K in a large magnetic field, the largest ever reported in
      any metallic systems. The STT characteristics of granular solids differ
      significantly from those of multilayers, showing no STT effect at low magnetic
      fields but prominent STT effects at high fields.

PMID- 16803202
TI  - Magnetic reversal of the ferroelectric polarization in a multiferroic spinel
      oxide.
AB  - Ferroelectric transition has been detected in a ferrimagnetic spinel oxide of
      CoCr2O4 upon the transition to the conical spin order below 25 K. The direction
      [110] of the spontaneous polarization is normal to both the magnetization easy
      axis [001] and to the propagation axis [110] of the transverse spiral component,
      in accord with the prediction based on the spin-current model. The reversal of
      the spontaneous magnetization by a small magnetic field (approximately 0.1 T)
      induces the reversal of the spontaneous polarization, indicating the clamping of
      the ferromagnetic and ferroelectric domain walls.

PMID- 16803203
TI  - Current-driven destabilization of both collinear configurations in asymmetric
      spin valves.
AB  - Spin-transfer torque in spin valves usually destabilizes one of the collinear
      configurations (either parallel or antiparallel) and stabilizes the second one.
      Apart from this, balance of the spin-transfer and damping torques can lead to
      steady precessional modes. In this Letter we show that in some asymmetric
      nanopillars, spin current can destabilize both parallel and antiparallel
      configurations. As a result, stationary precessional modes can occur at zero
      magnetic field. The corresponding phase diagram as well as frequencies of the
      precessional modes have been calculated in the framework of macrospin model. The
      relevant spin-transfer torque has been calculated in terms of the macroscopic
      model based on spin diffusion equations.

PMID- 16803204
TI  - Chemical contribution to surface-enhanced Raman scattering.
AB  - We present a new mechanism for the chemical contribution to surface-enhanced
      Raman scattering (SERS). The theory considers the modulation of the
      polarizability of a metal nanocluster or a flat metal surface by the vibrational
      motion of an adsorbed molecule. The modulated polarization of the substrate
      coupled with the incident light will contribute to the Raman scattering
      enhancement. We show that for a metal cluster and for a flat metal surface this
      new chemical contribution may enhance the Raman scattering intensity by a factor
      of approximately 102 and approximately 104, respectively. The new SERS process is
      determined by the electric field parallel to the surface of the metal substrate
      at the molecular binding site.

PMID- 16803205
TI  - Three-dimensional focusing of broadband microwave beams by a layered photonic
      structure.
AB  - Experiment and analysis confirm that a finite layered structure involving glass
      layers with broad strip metallizations can be characterized by broadband negative
      refractionlike behavior in three dimensions. The structure is further
      characterized as capable of 2:1 broadband focusing of near field radiation, with
      verified experimental focusing bandwidth of 1:5:1. This represents a significant
      improvement over the two-dimensional and narrow band focusing operation of
      current implementations of left-handed media. An electronic reconfigurable
      version is identified together with potential applications.

PMID- 16803206
TI  - Auger neutralization of He ions at an Al(100) surface using isotope effect.
AB  - He atoms and ions of the isotopes 3He and 4He are scattered with keV energies
      under a grazing angle of incidence from a flat and clean Al(100) surface. For the
      two isotopes we investigate Auger neutralization of incident He+ and He2+ ions
      via fractions of surviving ions. Pronounced effects for the different isotopes
      are observed which can be attributed to different time scales concerning the
      neutralization process of He ions in front of a metal surface. From the analysis
      of the data obtained for singly and doubly charged ions we find evidence that
      charge fractions for scattering of He+ ions from an Al surface result
      predominantly from a direct (Auger) electron capture event.

PMID- 16803207
TI  - Model for vacancy-induced d0 ferromagnetism in oxide compounds.
AB  - We propose a model with few parameters for vacancy-induced ferromagnetism based
      on a correlated model for oxygen orbitals with random potentials representing
      cation vacancies. For certain potentials, moments appear on oxygen sites near
      defects. Treating the randomness exactly, we calculate the magnetic couplings
      between moments, the Curie temperature and spin and charge densities as a
      function of the potential, the density of vacancies, and correlation strength.
      For physically reasonable parameters this predicts Curie temperatures well above
      room temperature for small concentrations of vacancies. We discuss our results in
      relation to questions of stability and reproducibility raised in experiments. To
      circumvent the difficulties of controlling intrinsic defects, we propose specific
      nonmagnetic host doping that could be, for example, substituted for cations in
      HfO2 or ZrO2.

PMID- 16803208
TI  - Interparticle potential and drag coefficient in nematic colloids.
AB  - Magneto-optic tweezers were used for measurements of liquid-crystal-mediated
      forces between spherical beads with tangential anchoring in thin nematic samples.
      Repulsive force, which results from the quadrupolar symmetry of defects around
      the immersed beads, decreases proportionally to 1/x6, with x being the bead
      separation. The velocity with which the particles are pushed apart also follows
      the same separation dependence. We thus find the effective drag coefficient
      gamma(eff) independent of x for surface-to-surface distances as small as 10% of
      the bead diameter.

PMID- 16803209
TI  - Helical structures from an isotropic homopolymer model.
AB  - We present Monte Carlo simulation results for square-well homopolymers at a
      series of bond lengths. Although the model contains only isotropic pairwise
      interactions, under appropriate conditions this system shows spontaneous chiral
      symmetry breaking, where the chain exists in either a left- or a right-handed
      helical structure. We investigate how this behavior depends upon the ratio
      between bond length and monomer radius.

PMID- 16803210
TI  - DNA damage induced by low-energy electrons: electron transfer and diffraction.
AB  - Thin films of the short single strand of DNA, GCAT, in which guanine (G) or
      adenine (A) have been removed, were bombarded under vacuum by 4 to 15 eV
      electrons. The fragments corresponding to base release and strand breaks (SB)
      were analyzed by high performance liquid chromatography and their yields compared
      with those obtained from unmodified GCAT. From such a comparison, it is shown
      that, using GCAT as a model system, (1) most SB result from electron capture by
      DNA bases followed by electron transfer to the phosphate group and (2) the
      initial capture probability depends on the coherence of the electron wave within
      the tetramer.

PMID- 16803211
TI  - Polymer packaging and ejection in viral capsids: shape matters.
AB  - We use a mesoscale simulation approach to explore the impact of different capsid
      geometries on the packaging and ejection dynamics of polymers of different
      flexibility. We find that both packing and ejection times are faster for flexible
      polymers. For such polymers a sphere packs more quickly and ejects more slowly
      than an ellipsoid. For semiflexible polymers, however, the case relevant to DNA,
      a sphere both packs and ejects more easily. We interpret our results by
      considering both the thermodynamics and the relaxational dynamics of the
      polymers. The predictions could be tested with biomimetic experiments with
      synthetic polymers inside artificial vesicles. Our results suggest that phages
      may have evolved to be roughly spherical in shape to optimize the speed of genome
      ejection, which is the first stage in infection.

PMID- 16803212
TI  - Partial phase synchronization for multivariate synchronizing systems.
AB  - Graphical models applying partial coherence to multivariate time series are a
      powerful tool to distinguish direct and indirect interdependencies in
      multivariate linear systems. We carry over the concept of graphical models and
      partialization analysis to phase signals of nonlinear synchronizing systems. This
      procedure leads to the partial phase synchronization index which generalizes a
      bivariate phase synchronization index to the multivariate case and reveals the
      coupling structure in multivariate synchronizing systems by differentiating
      direct and indirect interactions. This ensures that no false positive conclusions
      are drawn concerning the interaction structure in multivariate synchronizing
      systems. By application to the paradigmatic model of a coupled chaotic Roessler
      system, the power of the partial phase synchronization index is demonstrated.

PMID- 16803213
TI  - Passage times for unbiased polymer translocation through a narrow pore.
AB  - We study the translocation process of a polymer in the absence of external fields
      for various pore diameters b and membrane thickness L. The polymer performs Rouse
      and reptation dynamics. The mean translocation time (tau(t)) that the polymer
      needs to escape from a cell and the mean dwell time (tau(d)) that the polymer
      spends in the pore during the translocation process obey scaling relations in
      terms of the polymer length N, L, and b/R(g), where R(g) is the radius of
      gyration for the polymer. We explain these relations using simple arguments based
      on polymer dynamics and the equilibrium properties of polymers.

PMID- 16803214
TI  - Direct numerical simulations of electrophoresis of charged colloids.
AB  - We propose a numerical method to simulate electrohydrodynamic phenomena in
      charged colloidal dispersions. This method enables us to compute the time
      evolutions of colloidal particles, ions, and host fluids simultaneously by
      solving Newton, advection-diffusion, and Navier-Stokes equations so that the
      electrohydrodynamic couplings can be fully taken into account. The
      electrophoretic mobilities of charged spherical particles are calculated in
      several situations. The comparisons with approximation theories show quantitative
      agreements for dilute dispersions without any empirical parameters; however, our
      simulation predicts notable deviations in the case of dense dispersions.

PMID- 16803215
TI  - Epidemic dynamics on an adaptive network.
AB  - Many real-world networks are characterized by adaptive changes in their topology
      depending on the state of their nodes. Here we study epidemic dynamics on an
      adaptive network, where the susceptibles are able to avoid contact with the
      infected by rewiring their network connections. This gives rise to assortative
      degree correlation, oscillations, hysteresis, and first order transitions. We
      propose a low-dimensional model to describe the system and present a full local
      bifurcation analysis. Our results indicate that the interplay between dynamics
      and topology can have important consequences for the spreading of infectious
      diseases and related applications.

PMID- 16803216
TI  - Comment on "Atomistic view of the recombinative desorption of H2 from H/Si(100)".

PMID- 16803218
TI  - Comment on "Universal spin-flip transition in itinerant antiferromagnets".

PMID- 16803220
TI  - Strong-coupling polarons in dilute gas Bose-Einstein condensates.
AB  - A neutral impurity atom immersed in a dilute Bose-Einstein condensate (BEC) can
      have a bound ground state in which the impurity is self-localized. In this
      polaronlike state, the impurity distorts the density of the surrounding BEC,
      thereby creating the self-trapping potential minimum. We describe the self
      localization in a strong-coupling approach.

PMID- 16803221
TI  - One-dimensional interacting anyon gas: low-energy properties and Haldane
      exclusion statistics.
AB  - The low-energy properties of the one-dimensional anyon gas with a delta-function
      interaction are discussed in the context of its Bethe ansatz solution. It is
      found that the anyonic statistical parameter and the dynamical coupling constant
      induce Haldane exclusion statistics interpolating between bosons and fermions.
      Moreover, the anyonic parameter may trigger statistics beyond Fermi statistics
      for which the exclusion parameter alpha is greater than one. The Tonks-Girardeau
      and the weak coupling limits are discussed in detail. The results support the
      universal role of alpha in the dispersion relations.

PMID- 16803222
TI  - Tuning the Mott transition in a Bose-Einstein condensate by multiple photon
      absorption.
AB  - We study the time-dependent dynamics of a Bose-Einstein condensate trapped in an
      optical lattice. Modeling the system as a Bose-Hubbard model, we show how
      applying a periodic driving field can induce coherent destruction of tunneling.
      In the low-frequency regime, we obtain the novel result that the destruction of
      tunneling displays extremely sharp peaks when the driving frequency is resonant
      with the depth of the trapping potential ("multi-photon resonances"), which
      allows the quantum phase transition between the Mott insulator and the superfluid
      state to be controlled with high precision. We further show how the waveform of
      the field can be chosen to maximize this effect.

PMID- 16803223
TI  - Brownian refrigerator.
AB  - Onsager symmetry implies that a Brownian motor, driven by a temperature gradient,
      will also perform a refrigerator function upon loading. We analytically calculate
      the corresponding heat flow for an exactly solvable microscopic model and compare
      it with molecular dynamics simulations.

PMID- 16803224
TI  - Path summation formulation of the master equation.
AB  - Markovian dynamics, modeled by the kinetic master equation, has wide ranging
      applications in chemistry, physics, and biology. We derive an exact expression
      for the probability of a Markovian path in discrete state space for an arbitrary
      number of states and path length. The total probability of paths repeatedly
      visiting a set of states can be explicitly summed. The transition probability
      between states can be expressed as a sum over all possible paths connecting the
      states. The derived path probabilities satisfy the fluctuation theorem. The paths
      can be the starting point for a path space Monte Carlo procedure which can serve
      as an alternative algorithm to analyze pathways in a complex reaction network.

PMID- 16803225
TI  - Moduli-induced gravitino problem.
AB  - We investigate the cosmological moduli problem by studying a modulus decay in
      detail and find that the branching ratio of the gravitino production is
      generically of O(0.01-1), which causes another cosmological disaster.
      Consequently, the cosmological moduli problem cannot be solved simply by making
      the modulus mass heavier than 100 TeV. We also illustrate our results by
      explicitly calculating the branching ratio into the gravitinos in the mixed
      modulus-anomaly model.

PMID- 16803226
TI  - Constraints on light dark matter from core-collapse supernovae.
AB  - We show that light (approximately or = 1-30 MeV) dark matter particles can play a
      significant role in core-collapse supernovae, if they have relatively large
      annihilation and scattering cross sections, as compared to neutrinos. We find
      that if such particles are lighter than approximately or = 10 MeV and reproduce
      the observed dark matter relic density, supernovae would cool on a much longer
      time scale and would emit neutrinos with significantly smaller energies than in
      the standard scenario, in disagreement with observations. This constraint may be
      avoided, however, in certain situations for which the neutrino-dark-matter
      scattering cross sections remain comparatively small.

PMID- 16803229
TI  - Radiatively generated maximal mixing scenario for the Higgs boson mass and the
      least fine-tuned minimal supersymmetric standard model.
AB  - We argue that given the experimental constraints on the Higgs boson mass the
      least fine-tuned parameter space of the minimal supersymmetric standard model is
      with negative top-squark masses squared at the grand unification scale. While the
      top-squark mass squared is typically driven to positive values at the weak scale,
      the contribution to the Higgs boson mass squared parameter from the running can
      be arbitrarily small, which reduces the fine-tuning of electroweak symmetry
      breaking. At the same time the top-squark mixing is necessarily enhanced and the
      maximal mixing scenario for the Higgs boson mass can be generated radiatively
      even when starting with negligible mixing at the unification scale. This highly
      alleviates constraints on possible models for supersymmetry breaking in which
      fine-tuning is absent.

PMID- 16803231
TI  - System size and centrality dependence of charged hadron transverse momentum
      spectra in Au + Au and Cu + Cu collisions at square root of SNN = 62.4 and 200
      GeV.
AB  - We present transverse momentum distributions of charged hadrons produced in Cu +
      Cu collisions at square root of SNN = 62.4 and 200 GeV. The spectra are measured
      for transverse momenta of 0.25 < pT < 5.0 GeV/c at square root of SNN = 62.4 GeV
      and 0.25 < pT < 7.0 GeV/c at square root of SNN = 200 GeV, in a pseudorapidity
      range of 0.2 < eta < 1.4. The nuclear modification factor R(AA) is calculated
      relative to p + p data at both collision energies as a function of collision
      centrality. At a given collision energy and fractional cross section, R(AA) is
      observed to be systematically larger in Cu + Cu collisions compared to Au + Au.
      However, for the same number of participating nucleons, R(AA) is essentially the
      same in both systems over the measured range of pT, in spite of the significantly
      different geometries of the Cu + Cu and Au + Au systems.

PMID- 16803232
TI  - Effects of the carrier-envelope phase in the multiphoton ionization regime.
AB  - We theoretically investigate the effects of the carrier-envelope phase of few
      cycle laser pulses in the multiphoton ionization regime. For atoms with low
      ionization potential, total ionization yield barely exhibits phase dependence, as
      expected. However, population of some bound states clearly shows phase
      dependence. This implies that the measurement of the carrier-envelope phase would
      be possible through the photoemission between bound states without energy-and
      angle-resolved photoelectron detection. The considered scheme could be
      particularly useful to measure the carrier-envelope phase for a light source
      without an amplifier, such as a laser oscillator, which cannot provide sufficient
      pulse energy to induce tunneling ionization.

PMID- 16803233
TI  - Dynamics of low-energy electron attachment to formic acid.
AB  - Low-energy electrons (<2 eV) can fragment gas phase formic acid (HCOOH) molecules
      through resonant dissociative attachment processes. Recent experiments have shown
      that the principal reaction products of such collisions are formate ions (HCOO-)
      and hydrogen atoms. Using first-principles electron scattering calculations, we
      have identified the responsible negative ion state as a transient pi* anion.
      Symmetry considerations dictate that the associated dissociation dynamics are
      intrinsically polyatomic: a second anion surface, connected to the first by a
      conical intersection, is involved in the dynamics and the transient anion must
      necessarily deform to nonplanar geometries before it can dissociate to the
      observed stable products.

PMID- 16803234
TI  - Quantum homodyne tomography of a two-photon Fock state.
AB  - We present a continuous-variable experimental analysis of a two-photon Fock state
      of free-propagating light. This state is obtained from a pulsed nondegenerate
      parametric amplifier, which produces two intensity-correlated twin beams.
      Counting two photons in one beam projects the other beam in the desired two
      photon Fock state, which is analyzed by using a pulsed homodyne detection. The
      Wigner function of the measured state is clearly negative. We developed a
      detailed analytic model which allows a fast and efficient analysis of the
      experimental results.

PMID- 16803230
TI  - Search for the Theta+ pentaquark in the reaction gammad --> pK-K+n.
AB  - A search for the Theta+ in the reaction gammad --> pK-K+n was completed using the
      CLAS detector at Jefferson Lab. A study of the same reaction, published earlier,
      reported the observation of a narrow Theta+ resonance. The present experiment,
      with more than 30 times the integrated luminosity of our earlier measurement,
      does not show any evidence for a narrow pentaquark resonance. The angle
      integrated upper limit on Theta+ production in the mass range of 1.52-1.56 GeV/c2
      for the gammad --> pK-Theta+ reaction is 0.3 nb (95% C.L.). This upper limit
      depends on assumptions made for the mass and angular distribution of Theta+
      production. Using Lambda(1520) production as an empirical measure of rescattering
      in the deuteron, the cross section upper limit for the elementary gamman --> K
      Theta+ reaction is estimated to be a factor of 10 higher, i.e., approximately 3
      nb (95% C.L.).

PMID- 16803235
TI  - Surface wave generation and propagation on metallic subwavelength structures
      measured by far-field interferometry.
AB  - Transmission spectra of metallic films or membranes perforated by arrays of
      subwavelength slits or holes have been widely interpreted as resonance absorption
      by surface plasmon polaritons. Alternative interpretations involving evanescent
      waves diffracted on the surface have also been proposed. These two approaches
      lead to divergent predictions for some surface wave properties. Using far-field
      interferometry, we have carried out a series of measurements on elementary one
      dimensional subwavelength structures with the aim of testing key properties of
      the surface waves and comparing them to predictions of these two points of view.

PMID- 16803236
TI  - Devil's staircase in three-dimensional coherent waves localized on Lissajous
      parametric surfaces.
AB  - We experimentally demonstrate the significance of the longitudinal-transverse
      coupling in the mesoscopic regime by using a high-Q laser resonator as an analog
      experiment. The longitudinal-transverse coupling is found to lead to the three
      dimensional (3D) coherent waves that are localized on the parametric surfaces
      with Lissajous transverse patterns. More strikingly, experimental results reveal
      that the mode locking of the 3D coherent states forms a nearly complete Devil's
      staircase with the hierarchical ordering.

PMID- 16803237
TI  - Acoustic waves in an elastic channel near the free surface of granular media.
AB  - A theoretical description of a natural acoustical waveguide existing in
      unconsolidated granular materials due to a gravity-induced stiffness gradient is
      proposed. The analytical theory for the acoustic modes propagating in the medium
      with a power-law type inhomogeneity uses some original solutions of the Helmholtz
      equation that have not been derived before either in classical or in quantum
      mechanics. The dispersion relations and a physical mechanism of localization for
      these modes indicate their essential difference both from the Rayleigh surface
      acoustic waves and the waveguide modes in homogeneous plates.

PMID- 16803238
TI  - Localized states in bistable pattern-forming systems.
AB  - We present a unifying description close to a spatial bifurcation of localized
      states, appearing as large amplitude peaks nucleating over a pattern of lower
      amplitude. Localized states are pinned over a lattice spontaneously generated by
      the system itself. We show that the phenomenon is generic and requires only the
      coexistence of two spatially periodic states. At the onset of the spatial
      bifurcation, a forced amplitude equation is derived for the critical modes, which
      accounts for the appearance of localized peaks.

PMID- 16803239
TI  - Role of elastic stress in statistical and scaling properties of elastic
      turbulence.
AB  - The role of elastic stress in statistical and scaling properties of elastic
      turbulence in a polymer solution flow between two disks is discussed. The analogy
      with a small-scale magnetodynamics and a passive scalar turbulent advection in
      the Batchelor regime is used to explain the experimentally observed statistical
      properties, the flow structure, and the scaling of elastic turbulence. The
      emergence of a new length scale, namely, the boundary layer thickness, is
      observed and studied.

PMID- 16803240
TI  - New formulation of the equation for synchrotron oscillations.
AB  - We develop an orbit theory for synchrotron oscillations using the orbit length, ,
      as an independent variable. This is commonplace for static magnetic fields
      (storage rings). We extend this to the case of adiabatically varying magnetic
      fields (synchrotrons). Contrary to conventional treatments, betatron acceleration
      terms appear in both the energy and phase equations. We derive one-turn
      difference equations in the linear and adiabatic approximations. By a smooth
      approximation instead of the traveling-wave approximation, and by combining the
      two equations, we obtain a differential equation where the betatron acceleration
      terms are canceled. This equation is an extension of McMillan's equation to the
      case of strong-focusing synchrotrons.

PMID- 16803241
TI  - Resonance method of electric-dipole-moment measurements in storage rings.
AB  - A "resonance method" of measuring the electric dipole moment (EDM) of nuclei in
      storage rings is described, based on two new ideas: (1) Oscillating particles'
      velocities in resonance with spin precession, and (2) alternately producing two
      sub-beams with different betatron tunes--one sub-beam to amplify and thus make it
      easier to correct ring imperfections that produce false signals imitating EDM
      signals, and the other to make the EDM measurement.

PMID- 16803242
TI  - Laser-wakefield acceleration of monoenergetic electron beams in the first plasma
      wave period.
AB  - Beam profile measurements of laser-wakefield accelerated electron bunches reveal
      that in the monoenergetic regime the electrons are injected and accelerated at
      the back of the first period of the plasma wave. With pulse durations ctau >or=
      lambda(p), we observe an elliptical beam profile with the axis of the ellipse
      parallel to the axis of the laser polarization. This increase in divergence in
      the laser polarization direction indicates that the electrons are accelerated
      within the laser pulse. Reducing the plasma density (decreasing ctau/lambda(p))
      leads to a beam profile with less ellipticity, implying that the self-injection
      occurs at the rear of the first period of the plasma wave. This also demonstrates
      that the electron bunches are less than a plasma wavelength long, i.e., have a
      duration <25 fs. This interpretation is supported by 3D particle-in-cell
      simulations.

PMID- 16803243
TI  - Thermal conductivity of spin-polarized liquid 3He.
AB  - We present the first measurements of the thermal conductivity of spin-polarized
      normal liquid 3He. Using the rapid melting technique to produce nuclear
      polarizations up to 0.7, and a vibrating wire both as a heater and a thermometer,
      we show that, unlike the viscosity, the conductivity increases much less than
      predicted for s-wave scattering. We suggest that this might be due to a small
      probability for head-on collisions between quasiparticles.

PMID- 16803227
TI  - Search for Z' --> e+ e- using dielectron mass and angular distribution.
AB  - We search for Z' bosons in dielectron events produced in pp collisions at square
      root of s = 1.96 TeV, using 0.45 fb(-1) of data accumulated with the Collider
      Detector at Fermilab II detector at the Fermilab Tevatron. To identify the Z' -->
      e+ e- signal, both the dielectron invariant mass distribution and the angular
      distribution of the electron pair are used. No evidence of a signal is found, and
      95% confidence level lower limits are set on the Z' mass for several models.
      Limits are also placed on the mass and gauge coupling of a generic Z', as well as
      on the contact-interaction mass scales for different helicity structure
      scenarios.

PMID- 16803244
TI  - Twisted vortex state.
AB  - We study a twisted vortex bundle where quantized vortices form helices circling
      around the axis of the bundle in a "force-free" configuration. Such a state is
      created by injecting vortices into a rotating vortex-free superfluid. Using
      continuum theory we determine the structure and the relaxation of the twisted
      state. This is confirmed by numerical calculations. We also present experimental
      evidence of the twisted vortex state in superfluid 3He-B.

PMID- 16803246
TI  - X-ray absorption spectra of water from first principles calculations.
AB  - We present a series of ab initio calculations of the x-ray absorption cross
      section (XAS) of ice and liquid water at ambient conditions. Our results show
      that all available experimental data and theoretical results are consistent with
      the standard model of the liquid as comprising molecules with approximately four
      hydrogen bonds. Our simulations of ice XAS including the lowest lying excitonic
      state are in excellent agreement with experiment and those of a quasitetrahedral
      model of water are in reasonable agreement with recent measurements. Hence we
      propose that the standard, quasitetrahedral model of water, although approximate,
      represents a reasonably accurate description of the local structure of the
      liquid.

PMID- 16803245
TI  - Correlation of structural and electronic properties in a new low-dimensional form
      of mercury telluride.
AB  - Using high resolution electron microscopy and first principles quantum mechanical
      calculations we have explored the fundamental physics and chemistry of the
      semiconductor, HgTe grown inside single wall carbon nanotubes. This material
      forms a low-dimensional structure based on a repeating Hg2Te2 motif in which both
      atom species adopt new coordination geometries not seen in the bulk. Density
      functional theory calculations confirm the stability of this structure and
      demonstrate conclusively that it arises solely as a consequence of constrained
      low dimensionality. This change is directly correlated with a modified electronic
      structure in which the low-dimensional form of HgTe is transformed from a bulk
      semimetal to a semiconductor.

PMID- 16803247
TI  - Tunable nanoresonators constructed from telescoping nanotubes.
AB  - We have created a tunable mechanical nanoscale resonator with potential
      applications in precise mass, force, position, and frequency measurement. The
      device consists of a specially prepared multiwalled carbon nanotube (MWNT)
      suspended between a metal electrode and a mobile, piezo-controlled contact. By
      exploiting the unique telescoping ability of MWNTs, we controllably slide an
      inner nanotube core from its outer nanotube casing, effectively changing its
      length and tuning its flexural resonance frequency.

PMID- 16803228
TI  - Search for high-mass resonances decaying to emu in pp collisions at square root =
      1.69 TeV.
AB  - We describe a general search for resonances decaying to a neutral emu final state
      in pp collisions at a center-of-mass energy of 1.96 TeV. Using a data sample
      representing 344 pb(-1) of integrated luminosity recorded by the Collider
      Detector at Fermilab II experiment, we compare standard model predictions with
      the number of observed events for invariant masses between 50 and 800 GeV/c2.
      Finding no significant excess (5 events observed vs 7.7 +/- 0.8 expected for
      M(emu) > 100 GeV/c2 ), we set limits on sneutrino and Z' masses as functions of
      lepton family number violating couplings.

PMID- 16803248
TI  - Acoustic phonon emission from a weakly coupled superlattice under vertical
      electron transport: observation of phonon resonance.
AB  - We report measurements of acoustic phonon emission from a weakly coupled
      AlAs/GaAs superlattice (SL) under vertical electron transport. The phonons were
      detected using superconducting bolometers. A peak (resonance) was observed in
      emission parallel to the SL growth axis when the electrical energy drop per SL
      period matched the energy of the first SL mini-Brillouin zone-center phonon mode.
      This peak was mirrored by an increase of the differential conductance of the SL.
      These results are evidence for stimulated emission of terahertz phonons as
      previously predicted theoretically and suggest that such a SL may form the basis
      of a SASER (sound amplification by stimulated emission of radiation) device.

PMID- 16803249
TI  - Neutron phase imaging and tomography.
AB  - We report how a setup consisting of three gratings yields quantitative two- and
      three-dimensional images depicting the quantum-mechanical phase shifts of neutron
      de Broglie wave packets induced by the influence of macroscopic objects. Since
      our approach requires only a little spatial and chromatic coherence it provides a
      more than 2 orders of magnitude higher efficiency than existing techniques. This
      dramatically reduces the required measurement time for computed phase tomography
      and opens up the way for three-dimensional investigations of previously
      inaccessible quantum-mechanical phase interactions of neutrons with matter.

PMID- 16803250
TI  - Mechanical grain growth in nanocrystalline copper.
AB  - Nanograined materials have some unusual properties. To maintain the small size of
      the grains, grain growth should be avoided. But recently grain growth has been
      observed under an indenter at liquid-nitrogen temperatures. Such grain growth has
      never been reported before. How can this happen and how can it be prevented?
      These questions are answered here using a simple tilt boundary. It is found that
      high purity and nonequilibrium structure are necessary conditions for mechanical
      grain growth. The material must be pure enough so that free dislocations are
      available to move out of the boundary. But the boundary should not be in the
      lowest-energy state so that extra dislocations are available to be emitted by
      stress. Based on these conditions, methods can be devised to avoid low
      temperature grain growth.

PMID- 16803251
TI  - 4f delocalization in Gd: inelastic x-ray scattering at ultrahigh pressure.
AB  - We present resonant inelastic x-ray scattering and x-ray emission spectroscopy
      results on Gd metal to 113 GPa which suggest Kondo-like aspects in the
      delocalization of 4f electrons. Analysis of the resonant inelastic x-ray
      scattering data reveals a prolonged and continuous delocalization with volume
      throughout the entire pressure range, so that the volume-collapse transition at
      59 GPa is only part of the phenomenon. Moreover, the Lgamma1 x-ray emission
      spectroscopy spectra indicate no apparent change in the bare 4f moment across the
      collapse, suggesting that Kondo screening is responsible for the expected Pauli
      like behavior in magnetic susceptibility.

PMID- 16803252
TI  - Reverse-selective diffusion in nanocomposite membranes.
AB  - The permeability of certain polymer membranes with impenetrable nanoinclusions
      increases with the particle volume fraction [T. C. Merkel, Science 296, 519
      (2002)10.1126/science.1069580]. The discovery contradicts qualitative
      expectations based on Maxwell's classical theory of conduction or diffusion in
      composites with homogeneous phases. This Letter presents a theory based on an
      hypothesis that polymer chains are repelled from the inclusions during membrane
      casting. The accompanying increase in free volume, and hence solute diffusivity,
      yields bulk transport properties that are in good agreement with experiments.

PMID- 16803253
TI  - Structural depinning of Ne monolayers on Pb at T < 6/5 K.
AB  - We have studied the nanofriction of Ne monolayers with a quartz-crystal
      microbalance technique at temperatures below 6.5 K and in ultrahigh-vacuum
      conditions. Very homogeneous and smooth lead electrodes have been physically
      deposited on a quartz blank at 150 K and then annealed at room temperatures. With
      such a Pb-plated quartz-crystal microbalance, we have observed a pronounced
      depinning transition separating a low-coverage region, where the film is nearly
      locked to the oscillating electrode, from a high-coverage region characterized by
      slippage at the solid-fluid boundary. Such a behavior has been found to be very
      reproducible. These data are suggestive of a structural depinning of the solid Ne
      film when it becomes incommensurate with the lead substrate, in agreement with
      the results of an extensive molecular-dynamics study.

PMID- 16803254
TI  - Role of vacancies in the adsorption of quantum noble gases inside a bundle of
      carbon nanotubes.
AB  - Diffusion Monte Carlo calculations on the 4He and 20Ne adsorption in the
      interstices of a bundle of (10, 10) carbon nanotubes are reported. The results
      indicate that the presence of a carbon vacancy is enough, at least in some cases,
      to impede the adsorption of quantum gases in those systems. This could explain
      some discrepancies between the experimental data and the theoretical calculations
      about the possibility of adsorption of gases inside a bundle of carbon nanotubes.

PMID- 16803255
TI  - Pattern formation on carbon nanotube surfaces.
AB  - Calculations of fluorine binding and migration on carbon nanotube surfaces show
      that fluorine forms varying surface superlattices at increasing temperatures. The
      ordering transition is controlled by the surface migration barrier for fluorine
      atoms to pass through next neighbor sites on the nanotube, explaining the
      transition from semi-ionic low coverage to covalent high coverage fluorination
      observed experimentally for gas phase fluorination between 200 and 250 degrees C.
      The effect of solvents on fluorine binding and surface diffusion is explored.

PMID- 16803257
TI  - In-plane ferromagnetism in charge-ordering Na0.55CoO2.
AB  - The magnetic and transport properties are systematically studied on the single
      crystal Na(0.55)CoO2 with the resistivity divergence below 50 K. A weak
      ferromagnetic ordering is observed in susceptibility below 20 K with the magnetic
      field parallel to the Co-O plane, while no such ferromagnetic ordering is
      observed with the field perpendicular to the Co-O plane. It gives evidence for
      the existence of in-plane ferromagnetism below 20 K. The observed
      magnetoresistance of 30% at the field of 6 T at low temperatures indicates an
      unexpectedly strong spin-charge coupling in the triangle lattice NaxCoO2 system.

PMID- 16803256
TI  - Surface sensitivity in cluster-ion-induced sputtering.
AB  - The ion beam-induced removal of thin water ice films condensed onto Ag and
      bombarded by energetic Au, Au2, Au3, and C60 projectiles is examined both
      experimentally and with molecular dynamics computer simulations. For water
      overlayers of thicknesses greater than 10 A, the yields of sputtered Ag+
      secondary ions decay exponentially with increasing ice thickness, revealing
      characteristic decay lengths of 24, 20, 18, and 7.0 A, respectively. It is shown
      that these values manifest the characteristic depths of projectile energy loss,
      rather than escape depths of the sputtered Ag atoms through the water ice
      overlayer. Computer simulations show that the mechanism of ejection involves the
      sweeping away of overlayer water molecules, allowing for an unimpeded escape of
      ejected Ag atoms. The relevance of these data with respect to surface sensitivity
      in secondary ion mass spectrometry is discussed.

PMID- 16803259
TI  - Mixed Wannier-Bloch functions for electrons and phonons in periodic systems.
AB  - We introduce mixed Wannier-Bloch functions for studying electronic and
      vibrational spectra of periodic systems. These functions carry both spatial
      localization and limited spectral broadening, thereby combining the advantages of
      descriptions based on energy eigenstates (Bloch states) and position eigenstates
      (Wannier states). For the analysis of vibrational modes, a lattice position
      operator is introduced, analogous to the electronic Berry-phase position
      operator. Application to vitreous SiO2 demonstrates that mixed Wannier-Bloch
      functions constitute a powerful tool for tracking fingerprints of short- and
      medium-range structural order in electronic and vibrational spectra.

PMID- 16803258
TI  - Non-fermi liquid behavior in nearly charge ordered layered metals.
AB  - Non-Fermi liquid behavior is shown to occur in two-dimensional metals which are
      close to a charge ordering transition driven by the Coulomb repulsion. A linear
      temperature dependence of the scattering rate together with an increase of the
      electron effective mass occur above T*, a temperature scale much smaller than the
      Fermi temperature. It is shown that the anomalous temperature dependence of the
      optical conductivity of the quasi-two-dimensional organic metal alpha-(BEDT
      TTF)2MHg(SCN)4, with M = NH4 and Rb, above T* = 50-100K, agrees qualitatively
      with predictions for the electronic properties of nearly charge ordered two
      dimensional metals.

PMID- 16803260
TI  - Magnetic properties of spin-orbital polarons in lightly doped cobaltates.
AB  - We present a numerical treatment of a spin-orbital-polaron model for NaxCoO2 at
      small hole concentration (0.7 < x 1). We demonstrate how the polarons account for
      the peculiar magnetic properties of this layered compound: They explain the large
      susceptibility; their internal degrees of freedom lead both to a negative Curie
      Weiss temperature and yet to a ferromagnetic intralayer interaction, thereby
      resolving a puzzling contradiction between these observations. We make specific
      predictions on the momentum and energy location of excitations resulting from the
      internal degrees of freedom of the polaron, and discuss their impact on spin-wave
      damping.

PMID- 16803261
TI  - Low-lying quasiparticle states and hidden collective charge instabilities in
      parent cobaltate superconductors.
AB  - We report a state-of-the-art photoemission (angle-resolved photoemission
      spectroscopy) study of high quality single crystals of NaxCoO2 the series
      focusing on the fine details of the low-energy states. The Fermi velocity is
      found to be small (<0.5 eV A) and only weakly anisotropic over the Fermi surface
      at all dopings, setting the size of the pair wave function to be on the order of
      10-20 nm. In the low-doping regime, the exchange interlayer splitting vanishes
      and two-dimensional collective instabilities such as 120 degrees -type
      fluctuations become kinematically allowed. Our results suggest that the unusually
      small Fermi velocity and the unique symmetry of kinematic instabilities
      distinguish cobaltates from most other oxide superconductors.

PMID- 16803262
TI  - Full counting statistics of chiral Luttinger liquids with impurities.
AB  - We study the statistics of charge transfer through an impurity in a chiral
      Luttinger liquid (realized experimentally as a quantum point contact in a
      fractional quantum Hall edge state device). Taking advantage of the integrability
      we present a procedure for obtaining the cumulant generating function of the
      probability distribution to transfer a fixed amount of charge through the
      constriction. Using this approach we analyze in detail the behavior of the third
      cumulant C3 as a function of applied voltage, temperature, and barrier height. We
      predict that C3 can be used to measure the fractional charge at temperatures,
      which are several orders of magnitude higher than those needed to extract the
      fractional charge from the measurement of the second cumulant. Moreover, we
      identify the component of C3, which carries the information about the fractional
      charge.

PMID- 16803263
TI  - Thermodynamic density of states of two-dimensional GaAs systems near the apparent
      metal-insulator transition.
AB  - We perform combined resistivity and compressibility studies of two-dimensional
      hole and electron systems which show the apparent metal-insulator transition--a
      crossover in the sign of deltaR/deltaT with changing density. No thermodynamic
      anomalies have been detected in the crossover region. Instead, despite a tenfold
      difference in r(s), the compressibility of both electrons and holes is well
      described by the theory of nonlinear screening of the random potential. We show
      that the resistivity exhibits a scaling behavior near the percolation threshold
      found from analysis of the compressibility. Notably, the percolation transition
      occurs at a much lower density than the crossover.

PMID- 16803264
TI  - Electron-phonon interaction at the Si(111)-7 x 7 surface.
AB  - It is shown that electron-phonon interaction provides a natural explanation for
      the unusual band dispersion of the metallic surface states at the Si(111)-(7 x 7)
      surface. Angle-resolved photoemission reveals a discontinuity of the adatom band
      at a binding energy close to the dominant surface phonon mode at h(omega0) = 70
      meV. This mode has been assigned to adatom vibrations by molecular dynamics
      calculations. A calculation of the spectral function for electron-phonon
      interaction with this well-defined Einstein mode matches the data. Two
      independent determinations of the electron-phonon coupling parameter from the
      band dispersion and from the temperature-dependent phonon broadening yield
      similar values of lambda = 1.09 and lambda = 1.06.

PMID- 16803265
TI  - Nonequilibrium transport in quantum impurity models: the Bethe ansatz for open
      systems.
AB  - We develop an exact nonperturbative framework to compute steady-state properties
      of quantum impurities subject to a finite bias. We show that the steady-state
      physics of these systems is captured by nonequilibrium scattering eigenstates
      which satisfy an appropriate Lippman-Schwinger equation. Introducing a
      generalization of the equilibrium Bethe ansatz--the nonequilibrium Bethe ansatz-
      we explicitly construct the scattering eigenstates for the interacting resonance
      level model and derive exact, nonperturbative results for the steady-state
      properties of the system.

PMID- 16803266
TI  - Umklapp-mediated quantization of electronic states in Ag films on Ge(111).
AB  - We employ angle-resolved photoemission to study the electronic structure of
      atomically uniform films of Ag grown on Ge(111). A new kind of quantum well state
      is observed near a specific emission direction away from the surface normal. In
      contrast with the usual quantum well state arising from electron confinement by
      specular reflections at the surface and interface of the film, the new kind
      involves retroreflections, or umklapp reflections, at the interface. It requires
      four reflections, instead of the usual two reflections, to complete a coherent
      interference path.

PMID- 16803267
TI  - Compensation of effective field in the field-induced superconductor kappa
      (BETS)2FeBr4 observed by 77Se NMR.
AB  - We report results of 77Se NMR frequency shift in the normal state of the organic
      charge-transfer salt kappa-(BETS)2FeBr4 which shows magnetic field-induced
      superconductivity (FISC). From a simple mean-field analysis, we determined the
      field and the temperature dependences of the magnetization m(pi) of the pi
      conduction electrons on BETS molecules. We found that the Fe spins are
      antiferromagnetically coupled to the pi electrons and determined the exchange
      field to be J = -2.3T/microB. The exchange field from the fully saturated Fe
      moments (5 microB) is compensated by an external field of 12 T. This is close to
      the central field of the FISC phase, consistent with the Jaccarino-Peter local
      field-compensation mechanism for FISC [Phys. Rev. Lett. 9, 290 (1962)].

PMID- 16803268
TI  - Specific heat of the Ca-intercalated graphite superconductor CaC6.
AB  - The superconducting state of Ca-intercalated graphite CaC6 has been investigated
      by specific heat measurements. The characteristic anomaly at the superconducting
      transition (Tc = 11.4 K) indicates clearly the bulk nature of the
      superconductivity. The temperature and magnetic field dependence of the
      electronic specific heat are consistent with a fully gapped superconducting order
      parameter. The estimated electron-phonon coupling constant is lambda = 0.70 +/-
      0.04, suggesting that the relatively high Tc of CaC6 can be explained within the
      intermediate coupling BCS approach.

PMID- 16803269
TI  - Current controlled spin reversal of nanomagnets with giant uniaxial anisotropy.
AB  - Since a giant magnetic anisotropy of 9 meV per atom has been realized on a Pt
      surface, we use the kinetic Monte Carlo method to study the spin dynamics of a
      nanomagnet that is made by putting a line of such adatoms on a thin metallic
      strip so that the fixed spins are coupled very weakly and a spin-polarized
      current can be injected into the strip. There is a magnetization hysteresis
      versus the current because of the giant anisotropy. The hysteresis loop is
      diminished exponentially with the temperature increasing. The magnetization can
      be controlled by injecting a spin-polarized current.

PMID- 16803270
TI  - Time-resolved imaging of spin transfer switching: beyond the macrospin concept.
AB  - Time-resolved images of the magnetization switching process in a spin transfer
      structure, obtained by ultrafast x-ray microscopy, reveal the limitations of the
      macrospin model. Instead of a coherent magnetization reversal, we observe
      switching by lateral motion of a magnetic vortex across a nanoscale element. Our
      measurements reveal the fundamental roles played independently by the torques due
      to charge and spin currents in breaking the magnetic symmetry on picosecond time
      scales.

PMID- 16803271
TI  - Dynamic compressibility and aging in Wigner crystals and quantum glasses.
AB  - We study the nonequilibrium linear response of quantum elastic systems pinned by
      quenched disorder with Schwinger-Keldysh real-time techniques complemented by a
      mean-field variational approach. We find (i) a quasiequilibrium regime in which
      the analytic continuation from the imaginary-time replica results holds provided
      the marginality condition is enforced, and (ii) an aging regime. The conductivity
      and compressibility are computed. The latter is found to cross over from its
      dynamic to static value on a scale set by the waiting time after a quench, an
      effect which can be probed in experiments in, e.g., Wigner glasses.

PMID- 16803272
TI  - Overlap equivalence in the Edwards-Anderson model.
AB  - We study the relative fluctuations of the link overlap and the square standard
      overlap in the three-dimensional Gaussian Edwards-Anderson model with zero
      external field. We first analyze the correlation coefficient and find that the
      two quantities are uncorrelated above the critical temperature. Below the
      critical temperature we find that the link overlap has vanishing fluctuations for
      fixed values of the square standard overlap and large volumes. Our data show that
      the conditional variance scales to zero in the thermodynamic limit. This implies
      that, if one of the two random variables tends to a trivial one (i.e., deltalike
      distributed), then the other does also, and as a consequence, the "trivial
      nontrivial" picture should be dismissed. Our results show that the two overlaps
      are completely equivalent in the description of the low temperature phase of the
      Edwards-Anderson model.

PMID- 16803273
TI  - Asymmetric reversal in inhomogeneous magnetic heterostructures.
AB  - Asymmetric magnetization reversal is an unusual phenomenon in
      antiferromagnet/ferromagnet (AF/FM) exchange biased bilayers. We investigated
      this phenomenon in a simple model system experimentally and by simulation
      assuming inhomogeneously distributed interfacial AF moments. The results suggest
      that the observed asymmetry originates from the intrinsic broken symmetry of the
      system, which results in local incomplete domain walls parallel to the interface
      in reversal to negative saturation of the FM. The magneto-optical Kerr effect
      unambiguously confirms such an asymmetric reversal and a depth-dependent FM
      domain wall in accord with the magnetometry and simulations.

PMID- 16803274
TI  - Measurement of elastic forces between iron colloidal particles in a nematic
      liquid crystal.
AB  - The forces that arise between two iron particles in a nematic liquid crystal with
      a strong homeotropic anchoring were studied. For the first time, the short range
      repulsive force resulting from the presence of a hedgehog defect between two
      particles was precisely determined thanks to application of a small magnetic
      field and observation of the equilibrium position resulting from the balance
      between the elastic and magnetic forces. Above a given threshold force, the
      particles stuck together whereas the hedgehog defect was expelled and transformed
      into a Saturn ring located between the particles. The attractive part of the
      interparticle force was determined with the same method on the entire range of
      separation distances; we found that the equilibrium distance between two
      particles was r = 1.19 +/- 0.05 <d> (<d> was the average diameter of the pair of
      particles).

PMID- 16803275
TI  - Parity-breaking bifurcation and global oscillation in patterns of ion channels.
AB  - Stationary spatiotemporal pattern formation emerging from the electric activity
      of biological membranes is widespread in cells and tissues. A known key
      instability comes from the self-aggregation of membrane channels. In a two
      dimensional geometry, we show that the primary pattern undergoes four secondary
      instabilities: Eckhaus-like, period-halving, drift instabilities, and a global
      oscillation. The stability diagram is determined. The parity-breaking (drift)
      bifurcation of channel density is characterized analytically and numerically.

PMID- 16803276
TI  - Force-dependent fragility in RNA hairpins.
AB  - We apply Kramers theory to investigate the dissociation of multiple bonds under
      mechanical force and interpret experimental results for the unfolding and
      refolding force distributions of an RNA hairpin pulled at different loading rates
      using laser tweezers. We identify two different kinetic regimes depending on the
      range of forces explored during the unfolding and refolding process. The present
      approach extends the range of validity of the two-states approximation by
      providing a theoretical framework to reconstruct free-energy landscapes and
      identify force-induced structural changes in molecular transition states using
      single molecule pulling experiments. The method should be applicable to RNA
      hairpins with multiple kinetic barriers.

PMID- 16803277
TI  - Efficient computation of transition state resonances and reaction rates from a
      quantum normal form.
AB  - A quantum version of a recent formulation of transition state theory in phase
      space is presented. The theory developed provides an algorithm to compute quantum
      reaction rates and the associated Gamov-Siegert resonances with very high
      accuracy. The algorithm is especially efficient for multi-degree-of-freedom
      systems where other approaches are no longer feasible.

PMID- 16803278
TI  - Melting kinetics in polymers.
AB  - In polymers, it is possible to obtain single chain forming single crystals. It is
      feasible to melt these crystals by simple consecutive detachment of chain
      segments from the crystalline substrate and its diffusion into the melt. However,
      complication in the melting process occurs when the chain in the process of
      detachment from the surface is shared between different crystals. Experimentally,
      a clear distinction in different melting processes is observed, by the
      differences in the activation energies required for the consecutive detachment of
      chain segments or of segments having topological constraints. The consecutive
      detachment of free chain segments starts at the melting temperature predicted
      from the Gibbs-Thomson equation, whereas higher temperature or time is required
      if the chain has to overcome the constraints.

PMID- 16803279
TI  - Scale-free network growth by ranking.
AB  - Network growth is currently explained through mechanisms that rely on node
      prestige measures, such as degree or fitness. In many real networks, those who
      create and connect nodes do not know the prestige values of existing nodes but
      only their ranking by prestige. We propose a criterion of network growth that
      explicitly relies on the ranking of the nodes according to any prestige measure,
      be it topological or not. The resulting network has a scale-free degree
      distribution when the probability to link a target node is any power-law function
      of its rank, even when one has only partial information of node ranks. Our
      criterion may explain the frequency and robustness of scale-free degree
      distributions in real networks, as illustrated by the special case of the Web
      graph.

PMID- 16803280
TI  - Scaling of fluctuations in traffic on complex networks.
AB  - We study the scaling of fluctuations with the mean of traffic in complex networks
      using a model where the arrival and departure of "packets" follow exponential
      distributions, and the processing capability of nodes is either unlimited or
      finite. The model presents a wide variety of exponents between 1/2 and 1 for this
      scaling, revealing their dependence on the few parameters considered, and
      questioning the existence of universality classes. We also report the
      experimental scaling of the fluctuations in the Internet for the Abilene backbone
      network. We found scaling exponents between 0.71 and 0.86 that do not fit with
      the exponent 1/2 reported in the literature.

PMID- 16803281
TI  - Comment on "Surface plasmon modes and the Casimir energy".

PMID- 16803283
TI  - Comment on "Hausdorff dimension of critical fluctuations in Abelian gauge
      theories".

PMID- 16803285
TI  - Comment on "Effective long-range attraction between protein molecules in solution
      studied by small angle neutron scattering".

PMID- 16803287
TI  - Comment on "Thermotropic biaxial nematic liquid crystals".

PMID- 16803289
TI  - Eckhaus instability in systems with large delay.
AB  - The dynamical behavior of various physical and biological systems under the
      influence of delayed feedback or coupling can be modeled by including terms with
      delayed arguments in the equations of motion. In particular, the case of long
      delay may lead to complicated and high-dimensional dynamics. We investigate the
      effects of delay in systems that display an oscillatory instability (Hopf
      bifurcation) in the absence of delay. We show by analytical and numerical methods
      that the dynamical scenario includes the coexistence of multiple stable periodic
      solutions and can be described in terms of the Eckhaus instability, which is well
      known in the context of spatially extended systems.

PMID- 16803290
TI  - Casimir effect for curved geometries: proximity-force-approximation validity
      limits.
AB  - We compute Casimir interaction energies for the sphere-plate and cylinder-plate
      configuration induced by scalar-field fluctuations with Dirichlet boundary
      conditions. Based on a high-precision calculation using world-line numerics, we
      quantitatively determine the validity bounds of the proximity-force approximation
      (PFA) on which the comparison between all corresponding experiments and theory
      are based. We observe the quantitative failure of the PFA on the 1% level for a
      curvature parameter a/R>0.00755. Even qualitatively, the PFA fails to predict
      reliably the correct sign of genuine Casimir curvature effects. We conclude that
      data analysis of future experiments aiming at a precision of 0.1% must no longer
      be based on the PFA.

PMID- 16803291
TI  - Processor core model for quantum computing.
AB  - We describe an architecture based on a processing "core," where multiple qubits
      interact perpetually, and a separate "store," where qubits exist in isolation.
      Computation consists of single qubit operations, swaps between the store and the
      core, and free evolution of the core. This enables computation using physical
      systems where the entangling interactions are "always on." Alternatively, for
      switchable systems, our model constitutes a prescription for optimizing many
      qubit gates. We discuss implementations of the quantum Fourier transform,
      Hamiltonian simulation, and quantum error correction.

PMID- 16803292
TI  - Information-disturbance tradeoff in estimating a maximally entangled state.
AB  - We derive the amount of information retrieved by a quantum measurement in
      estimating an unknown maximally entangled state, along with the pertaining
      disturbance on the state itself. The optimal tradeoff between information and
      disturbance is obtained, and a corresponding optimal measurement is provided.

PMID- 16803293
TI  - General monogamy inequality for bipartite qubit entanglement.
AB  - We consider multipartite states of qubits and prove that their bipartite quantum
      entanglement, as quantified by the concurrence, satisfies a monogamy inequality
      conjectured by Coffman, Kundu, and Wootters. We relate this monogamy inequality
      to the concept of frustration of correlations in quantum spin systems.

PMID- 16803294
TI  - Experimental quantum error rejection for quantum communication.
AB  - We report an experimental demonstration of a bit-flip error-rejection protocol
      for error-reduced transfer of quantum information through a noisy quantum
      channel. In the experiment, an unknown state to be transmitted is encoded into a
      two-photon entangled state, which is then sent through an engineered noisy
      quantum channel. At the final stage, the unknown state is decoded by a parity
      measurement, successfully rejecting the erroneous transmission over the noisy
      quantum channel.

PMID- 16803295
TI  - Experimental entanglement distillation of two-qubit mixed states under local
      operations.
AB  - We experimentally demonstrate optimal entanglement distillation from two forms of
      two-qubit mixed states under local filtering operations according to the
      constructive method introduced by [F. Verstraete, Phys. Rev. A 64, 010101(R)
      (2001)10.1103/PhysRevA.64.010101]. In principle, our setup can be easily applied
      to distilling entanglement from arbitrary two-qubit partially mixed states. We
      also test the violation of the Clauser-Horne-Shinmony-Holt inequality for the
      distilled state from the first form of mixed state to show its "hidden
      nonlocality."

PMID- 16803296
TI  - Criticality, the area law, and the computational power of projected entangled
      pair states.
AB  - The projected entangled pair state (PEPS) representation of quantum states on two
      dimensional lattices induces an entanglement based hierarchy in state space. We
      show that the lowest levels of this hierarchy exhibit a very rich structure
      including states with critical and topological properties. We prove, in
      particular, that coherent versions of thermal states of any local 2D classical
      spin model correspond to such PEPS, which are in turn ground states of local 2D
      quantum Hamiltonians. This correspondence maps thermal onto quantum fluctuations,
      and it allows us to analytically construct critical quantum models exhibiting a
      strict area law scaling of the entanglement entropy in the face of power law
      decaying correlations. Moreover, it enables us to show that there exist PEPS
      which can serve as computational resources for the solution of NP-hard problems.

PMID- 16803297
TI  - 3D quantum gravity and effective noncommutative quantum field theory.
AB  - We show that the effective dynamics of matter fields coupled to 3D quantum
      gravity is described after integration over the gravitational degrees of freedom
      by a braided noncommutative quantum field theory symmetric under a kappa
      deformation of the Poincare group.

PMID- 16803298
TI  - Searching for CPT violation with cosmic microwave background data from WMAP and
      BOOMERANG.
AB  - We search for signatures of Lorentz and violations in the cosmic microwave
      background (CMB) temperature and polarization anisotropies by using the Wilkinson
      Microwave Anisotropy Probe (WMAP) and the 2003 flight of BOOMERANG (B03) data. We
      note that if the Lorentz and symmetries are broken by a Chern-Simons term in the
      effective Lagrangian, which couples the dual electromagnetic field strength
      tensor to an external four-vector, the polarization vectors of propagating CMB
      photons will get rotated. Using the WMAP data alone, one could put an interesting
      constraint on the size of such a term. Combined with the B03 data, we found that
      a nonzero rotation angle of the photons is mildly favored: [Formula: See Text].

PMID- 16803299
TI  - Background independent duals of the harmonic oscillator.
AB  - We show that a class of topological field theories are quantum duals of the
      harmonic oscillator. This is demonstrated by establishing a correspondence
      between the creation and annihilation operators and nonlocal gauge invariant
      observables of the topological field theory. The example is used to discuss some
      issues concerning background independence and the relation of vacuum energy to
      the problem of time in quantum gravity.

PMID- 16803302
TI  - Solving pure yang-mills theory in dimensions.
AB  - We analytically compute the spectrum of the spin zero glueballs in the planar
      limit of pure Yang-Mills theory in 2 + 1 dimensions. The new ingredient is
      provided by our computation of a new nontrivial form of the ground state wave
      functional. The mass spectrum of the theory is determined by the zeroes of Bessel
      functions, and the agreement with large lattice data is excellent.

PMID- 16803300
TI  - Observation of b-->dgamma and determination of /Vtd/Vts/.
AB  - We report the observation of the flavor-changing neutral current process b-
      >dgamma using a sample of 386 x 106 B meson pairs accumulated by the Belle
      detector at the KEKB e+e- collider. We measure branching fractions for the
      exclusive modes B--->rho-gamma, B0rho0gamma, and B0omegagamma. Assuming that
      these three modes are related by isospin, we find B(B-
      >(rho,gamma)gamma)=[Formula: See Text] with a significance of 5.1sigma. This
      result is used to determine the ratio of Cabibbo-Kobayashi-Maskawa matrix
      elements /Vtd/Vts/ to be [Formula: See Text].

PMID- 16803303
TI  - Unquenched complex dirac spectra at nonzero chemical potential: two-color QCD
      lattice data versus matrix model.
AB  - We compare analytic predictions of non-Hermitian chiral random matrix theory with
      the complex Dirac operator eigenvalue spectrum of two-color lattice gauge theory
      with dynamical fermions at nonzero chemical potential. The Dirac eigenvalues come
      in complex conjugate pairs, making the action of this theory real and positive
      for our choice of two staggered flavors. This enables us to use standard Monte
      Carlo simulations in testing the influence of the chemical potential and quark
      mass on complex eigenvalues close to the origin. We find excellent agreement
      between the analytic predictions and our data for two different volumes over a
      range of chemical potentials below the chiral phase transition. In particular, we
      detect the effect of unquenching when going to very small quark masses.

PMID- 16803305
TI  - Electron-impact ionization and excitation of helium to the n=1-4 ionic states.
AB  - We present high-precision (e,2e) measurements and calculations for the e-He four
      body Coulomb breakup problem. Cross-section ratios for ionization and excitation
      of the first three excited states of He+ relative to the ground state have been
      measured for incident energies between 112 and 319 eV. Comparing the data with
      predictions from a state-of-the-art hybrid distorted-wave+convergent R matrix
      with pseudostates (close coupling) approach shows that treating the projectile
      target interaction at least to second order is crucial to obtain reasonable
      agreement between theory and experiment. Nevertheless, our benchmark studies
      reveal significant theoretical problems for the symmetric energy-sharing cases,
      thus indicating the need for further improvement.

PMID- 16803306
TI  - Diamagnetic response of metallic photonic crystals at infrared and visible
      frequencies.
AB  - We show analytically and numerically that diamagnetic response (effective
      magnetic permeability mue<1) at infrared and visible frequencies can be achieved
      in photonic crystals composed of metallic nanowires or nanospheres when the
      wavelength is much larger than the lattice constant a (lambda approximately
      2000a). When lambda approximately100a, the metallic photonic crystals will
      exhibit strong diamagnetic response (mue<0.8), leading to many interesting
      phenomena such as the unusual Brewster angle for s waves and incident-angle-and
      polarization-independent reflection and transmission.

PMID- 16803307
TI  - Role of many-electron dynamics in high harmonic generation.
AB  - High harmonic generation (HHG) in many-electron atoms is studied theoretically.
      The breakdown of the frozen-core single active electron approximation is
      demonstrated, as it predicts roughly the same radiation amplitude in all noble
      gases. This is in contradiction with experiments, where heavier noble gases are
      known to emit much stronger HHG radiation than lighter ones. This experimental
      behavior of the noble gases can be qualitatively reproduced when many-electron
      dynamics, within a simple approximation, is taken into account.

PMID- 16803308
TI  - Band-gap guidance in optically induced photonic lattices with a negative defect.
AB  - We report the first experimental demonstration of band-gap guidance of light in
      an optically induced two-dimensional photonic lattice with a single-site negative
      defect (akin to a low-index core in photonic-crystal fibers). We discuss the
      difference between spatial guidance at a regular and a defect site, and show that
      the guided beam through the defect displays fine structures such as vortex cells
      that arise from defect modes excited at higher band gaps. Defect modes at
      different wavelengths are also observed.

PMID- 16803309
TI  - Coherence current, coherence vortex, and the conservation law of coherence.
AB  - Introducing scalar and vector densities for a mutual coherence function, we
      present a new conservation law for optical coherence of scalar wave fields in the
      form of a continuity equation. This coherence conservation law provides new
      insights into topological phenomena for the complex coherence function. Some
      properties related to the newly introduced coherence vector density, such as a
      circulating coherence current associated with a coherence vortex, are
      investigated both theoretically and experimentally for the first time.

PMID- 16803310
TI  - Controlled multibubble surface cavitation.
AB  - Heterogeneous bubble nucleation at surfaces has been notorious because of its
      irreproducibility. Here controlled multibubble surface cavitation is achieved by
      using a hydrophobic surface patterned with microcavities. The expansion of the
      nuclei in the microcavities is triggered by a fast lowering of the liquid
      pressure. The procedure allows us to control and fix the bubble distance within
      the bubble cluster. We observe a perfect quantitative reproducibility of the
      cavitation events where the inner bubbles in the two-dimensional cluster are
      shielded by the outer ones, reflected by their later expansion and their delayed
      collapse. Apart from the final bubble collapse phase (when jetting flows directed
      towards the cluster's center develop), the bubble dynamics can be quantitatively
      described by an extended Rayleigh-Plesset equation, taking pressure modification
      through the surrounding bubbles into account.

PMID- 16803311
TI  - Charge inversion at high ionic strength studied by streaming currents.
AB  - We report charge inversion, the sign reversal of the effective surface charge in
      the presence of multivalent counterions, for the biologically relevant regimes of
      divalent ions and mixtures of monovalent and multivalent ions. Using streaming
      currents, the pressure-driven transport of countercharges in the diffuse layer,
      we find that charge inversion occurs in rectangular silica nanochannels at high
      concentrations of divalent ions. Strong monovalent screening is found to cancel
      charge inversion, restoring the original surface charge polarity. An analytical
      model based on ion correlations successfully describes our observations.

PMID- 16803304
TI  - Azimuthal angle correlations for rapidity separated Hadron pairs in d+Au
      collisions at square root of sNN=200 GeV.
AB  - Deuteron-gold (d+Au) collisions at the Relativistic Heavy Ion Collider provide
      ideal platforms for testing QCD theories in dense nuclear matter at high energy.
      In particular, models suggesting strong saturation effects for partons carrying
      small nucleon momentum fraction (x) predict modifications to jet production at
      forward rapidity (deuteron-going direction) in d+Au collisions. We report on two
      particle azimuthal angle correlations between charged hadrons at forward/backward
      (deuteron/gold going direction) rapidity and charged hadrons at midrapidity in
      d+Au and p+p collisions at square root of sNN=200 GeV. Jet structures observed in
      the correlations are quantified in terms of the conditional yield and angular
      width of away-side partners. The kinematic region studied here samples partons in
      the gold nucleus with x~0.1 to ~0.01. Within this range, we find no x dependence
      of the jet structure in d+Au collisions.

PMID- 16803312
TI  - Lattice boltzmann versus molecular dynamics simulation of nanoscale hydrodynamic
      flows.
AB  - A fluid flow in a simple dense liquid, passing an obstacle in a two-dimensional
      thin film geometry, is simulated by molecular dynamics (MD) computer simulation
      and compared to results of lattice Boltzmann (LB) simulations. By the appropriate
      mapping of length and time units from LB to MD, the velocity field as obtained
      from MD is quantitatively reproduced by LB. The implications of this finding for
      prospective LB-MD multiscale applications are discussed.

PMID- 16803313
TI  - Spatiotemporal growing wave fronts in spatially stable boundary layers.
AB  - In fluid dynamical systems, it is not known a priori whether disturbances grow
      either in space or in time or as spatiotemporal structures. For a zero pressure
      gradient boundary layer (also known as the Blasius boundary layer), it is
      customary to treat it as a spatial problem, and some limited comparison between
      prediction and laboratory experiments exist. In the present work, the two
      dimensional receptivity problem of a Blasius boundary layer excited by a
      localized harmonic source is investigated under the general spatiotemporal
      framework, by using the Bromwich contour integral method. While this approach is
      seen to be equivalent to the spatial study for unstable systems, here we show for
      the first time how spatially stable systems show spatiotemporally growing wave
      fronts.

PMID- 16803314
TI  - Cross-stream migration of flexible molecules in a nanochannel.
AB  - Molecular dynamics simulations are used to examine the cross-stream chain
      migration phenomenon in dilute polymer solutions that are flowing in
      nanochannels. In particular, both uniform planar shear (Couette) and pressure
      driven (Poiseuille) flows of a dilute polymer solution are studied using a bead
      spring representation of polymer chains and a coarse grained model for the
      solvent. Our results show that three mechanisms govern the migration of
      deformable molecules in a nanochannel: (1) chain-wall hydrodynamic interactions,
      (2) thermal diffusion, and (3) gradient in chain mobility. These results are
      discussed in the context of recent experimental, numerical and theoretical work.

PMID- 16803315
TI  - High-gain lasing and polarization switch with a distributed optical-klystron free
      electron laser.
AB  - This Letter reports the first experimental results from the world's first
      distributed optical-klystron (DOK) free-electron laser (FEL), the DOK-1 FEL, at
      Duke University. The DOK-1 FEL is a hybrid system, comprised of four wigglers:
      two horizontal and two helical. With the DOK-1 FEL, we have obtained the highest
      FEL gain among all storage ring based FELs at 47.8% (+/-2.7%) per pass. We have
      also demonstrated that the FEL gain can be enhanced by increasing electron
      bunching using wigglers with a different polarization. Furthermore, we have
      realized controlled polarization switches of the FEL beam by a nonoptical means
      through the manipulation of a buncher magnet.

PMID- 16803316
TI  - Autoresonant phase-space holes in plasmas.
AB  - Electron phase-space holes are formed and controlled in a plasma by adiabatic
      nonlinear phase locking (autoresonance) with a chirped frequency driving wave.
      The process has a threshold on the driving amplitude and involves dragging a void
      region in phase space into the bulk of the distribution via persistent Cherenkov
      type resonance.

PMID- 16803317
TI  - Observation of plasma toroidal-momentum dissipation by neoclassical toroidal
      viscosity.
AB  - Dissipation of plasma toroidal angular momentum is observed in the National
      Spherical Torus Experiment due to applied nonaxisymmetric magnetic fields and
      their plasma-induced increase by resonant field amplification and resistive wall
      mode destabilization. The measured decrease of the plasma toroidal angular
      momentum profile is compared to calculations of nonresonant drag torque based on
      the theory of neoclassical toroidal viscosity. Quantitative agreement between
      experiment and theory is found when the effect of toroidally trapped particles is
      included.

PMID- 16803318
TI  - Momentum-resolved electron-phonon interaction in lead determined by neutron
      resonance spin-echo spectroscopy.
AB  - Neutron resonance spin-echo spectroscopy was used to monitor the temperature
      evolution of the linewidths of transverse acoustic phonons in lead across the
      superconducting transition temperature over an extended range of the Brillouin
      zone. For phonons with energies below the superconducting energy gap, a linewidth
      reduction of maximum amplitude was observed below . The electron-phonon
      contribution to the phonon lifetime extracted from these data is in satisfactory
      overall agreement with ab initio lattice-dynamical calculations, but significant
      deviations are found.

PMID- 16803319
TI  - Do binary hard disks exhibit an ideal glass transition?
AB  - We demonstrate that there is no ideal glass transition in a binary hard-disk
      mixture by explicitly constructing an exponential number of jammed packings with
      densities spanning the spectrum from the accepted amorphous glassy state to the
      phase-separated crystal. Thus the configurational entropy cannot be zero for an
      ideal amorphous glass, presumed distinct from the crystal in numerous theoretical
      and numerical estimates in the literature. This objection parallels our previous
      critique of the idea that there is a most-dense random (close) packing for hard
      spheres [Torquato, Phys. Rev. Lett. 84, 2064 (2000)10.1103/PhysRevLett.84.2064].

PMID- 16803320
TI  - Isotope dependence of the lifetime of the vibration of oxygen in silicon.
AB  - By simply changing the isotopes of the Si atoms that neighbor an oxygen Oi atom
      in crystalline silicon, the measured decay rate tau of the asymmetric-stretch
      vibration (nu3=1136 cm-1) of oxygen (Oi) in silicon changes by a factor of
      approximately 2.5. These data establish that nu3 decays by creating one nu1
      symmetric-stretch, local-vibrational mode of the Si-Oi-Si structure. If the
      residual energy (nu3-nu1) is less than the maximum frequency num of the host
      lattice, as for 28Si-16O-28Si in natural silicon, then it is emitted as one
      lattice mode, and tau depends on the density of one-phonon states at nu3-nu1. If
      (nu3-nu1)>num, as for 16O in single-isotope 30Si silicon, two lattice modes are
      created in addition to nu1, increasing tau. Prediction of tau for a particular
      defect clearly requires a detailed knowledge of that defect.

PMID- 16803301
TI  - Determinations of from inclusive semileptonic decays with reduced model
      dependence.
AB  - We report two novel determinations of /|Vub/ with reduced model dependence, based
      on measurements of the mass distribution of the hadronic system in semileptonic B
      decays. Events are selected by fully reconstructing the decay of one B meson and
      identifying a charged lepton from the decay of the other B meson from Upsilon(4S)
      ->BB events. In one approach, we combine the inclusive B-->Xulambdav rate,
      integrated up to a maximum hadronic mass mX<1.67 GeV/c2, with a measurement of
      the inclusive B-->Xsgamma photon energy spectrum. We obtain /Vub/=(4.43+/
      0.38stat+/-0.25syst+/-0.29theo) x 10-3. In another approach we measure the total
      B-->Xulambdav rate over the full phase space and find /Vub/=(3.84+/-0.70stat+/
      0.30syst+/-0.10theo) x 10-3.

PMID- 16803321
TI  - Phase-field crystals with elastic interactions.
AB  - We report on a novel extension of the recently introduced phase-field crystal
      (PFC) method [Elder, Phys. Rev. Lett. 88, 245701
      (2002)10.1103/PhysRevLett.88.245701], which incorporates elastic interactions as
      well as crystal plasticity and diffusive dynamics. In our model, elastic
      interactions are mediated through wave modes that propagate on time scales many
      orders of magnitude slower than atomic vibrations but still much faster than
      diffusive time scales. This allows us to preserve the quintessential advantage of
      the PFC model: the ability to simulate atomic-scale interactions and dynamics on
      time scales many orders of magnitude longer than characteristic vibrational time
      scales. We demonstrate the two different modes of propagation in our model and
      show that simulations of grain growth and elastoplastic deformation are
      consistent with the microstructural properties of nanocrystals.

PMID- 16803323
TI  - Role of lateral alkyl chains in modulation of molecular structures on metal
      surfaces.
AB  - We use low energy electron diffraction, scanning tunneling microscopy, first
      principles density-functional theory, and molecular mechanics calculations to
      analyze the adsorption and growth of quinacridone derivatives (QA) with alkyl
      chains of 4 and 16 carbon atoms on a Ag(110) substrate. Surprisingly, we find
      that the alkyl chains determine the orientation of the molecular overlayers.
      While the interaction of QA and the Ag substrate is primarily due to chemical
      bonding of oxygen to the silver substrate, determining the molecular orientation
      and preferred adsorption site, the intermolecular arrangement can be adjusted via
      the length of alkyl chains. We are thus able to fabricate uniform QA films with
      very well controlled physical properties.

PMID- 16803322
TI  - Beyond finite-size scaling in solidification simulations.
AB  - Although computer simulation has played a central role in the study of nucleation
      and growth since the earliest molecular dynamics simulations almost 50 years ago,
      confusion surrounding the effect of finite size on such simulations has limited
      their applicability. Modeling solidification in molten tantalum on the Blue
      Gene/L computer, we report here on the first atomistic simulation of
      solidification that verifies independence from finite-size effects during the
      entire nucleation and growth process, up to the onset of coarsening. We show that
      finite-size scaling theory explains the observed maximal grain sizes for systems
      up to about 8 000 000 atoms. For larger simulations, a crossover from finite-size
      scaling to more physical size-independent behavior is observed.

PMID- 16803324
TI  - Quantum size effect on the diffusion barriers and growth morphology of
      Pb/Si(111).
AB  - An intriguing growth morphology of Pb islands on a Si(111) surface is observed in
      our STM experiments: the growth of a Pb layer on Pb islands with unstable heights
      starts from the periphery and moves towards the center, while the nucleation of
      the next layer on stable Pb islands starts away from the periphery. Using first
      principles total energy calculations, we have studied the diffusion barriers of
      Pb adatoms on a freestanding Pb(111) film as a function of film thickness. The
      diffusion barriers are found to be very low (<60 meV), and a bi-layer oscillation
      due to the quantum size effect (QSE) is observed, with a lower barrier on the odd
      layered, relatively unstable Pb films. The diffusion barrier difference between
      the odd- and even-layered film is as large as 40 meV. The observed unusual growth
      can be attributed to this big difference in the diffusion barriers due to QSE.

PMID- 16803325
TI  - Dendrochronology of strain-relaxed islands.
AB  - We report on the observation and study of tree-ring structures below dislocated
      SiGe islands (superdomes) grown on Si(001) substrates. Analogous to the study of
      tree rings (dendrochronology), these footprints enable us to gain unambiguous
      information on the growth and evolution of superdomes and their neighboring
      islands. The temperature dependence of the critical volume for dislocation
      introduction is measured and related to the composition of the islands. We show
      clearly that island coalescence is the dominant pathway towards dislocation
      nucleation at low temperatures, while at higher temperatures anomalous coarsening
      is effective and leads to the formation of a depletion region around superdomes.

PMID- 16803326
TI  - Nonequilibrium interlayer transport in pulsed laser deposition.
AB  - We use time-resolved surface x-ray diffraction measurements with microsecond
      range resolution to study the growth kinetics of pulsed laser deposited . Time
      dependent surface coverages corresponding to single laser shots were determined
      directly from crystal truncation rod intensity transients. Analysis of surface
      coverage evolution shows that extremely fast nonequilibrium interlayer transport,
      which occurs concurrently with the arrival of the laser plume, dominates the
      deposition process. A much smaller fraction of material, which is governed by the
      dwell time between successive laser shots, is transferred by slow, thermally
      driven interlayer transport processes.

PMID- 16803327
TI  - Surface reconstructions of TiO2(110) driven by suboxides.
AB  - Scanning tunneling microscopy and density functional theory are used to develop a
      new structural model for surface reconstructions driven by Ti interstitials on
      TiO2(110). Ti interstitials form the edge- or face-sharing octahedra that serve
      as building blocks for (1 x 1) reconstruction. Thus, contrary to conventional
      wisdom, the 1 x 1 periodicity is insufficient to establish the correct surface
      stoichiometry. Furthermore, in our structural and compositional model the
      reversible oxidation or reduction between (1 x 1) and (1 x 2) is entirely
      achieved by transfer of the added rows.

PMID- 16803328
TI  - Interplay between thermodynamics and kinetics in the capping of InAs/GaAs(001)
      quantum dots.
AB  - A microscopic picture for the GaAs overgrowth of self-organized quantum dots is
      developed. Scanning tunneling microscopy measurements reveal two capping regimes:
      the first being characterized by a dot shrinking and a backward pyramid-to-dome
      shape transition. This regime is governed by fast dynamics resulting in island
      morphologies close to thermodynamic equilibrium. The second regime is marked by a
      true overgrowth and is controlled by kinetically limited surface diffusion
      processes. A simple model is developed to describe the observed structural
      changes which are rationalized in terms of energetic minimization driven by
      lattice mismatch and alloying.

PMID- 16803329
TI  - Superconductivity dependent friction of water, nitrogen, and superheated He films
      adsorbed on Pb(111).
AB  - We report a quartz crystal microbalance study of sliding friction levels in N2,
      H2O, and superheated He films adsorbed on Pb(111) substrates alternating in and
      out of the superconducting state. Reductions in friction upon entry into the
      superconducting state are greater for N2 than He, consistent with a recent theory
      that linked electronic friction to adsorbate polarizability. Our work also
      reveals that repetitive cycling of an externally applied magnetic field may
      impact friction.

PMID- 16803330
TI  - Cu2O island shape transition during Cu-Au alloy oxidation.
AB  - In situ transmission electron microscopy observations of the oxidation of (001)
      Cu-Au alloys indicate that the Cu2O islands that form undergo a remarkable
      transformation from an initially compact morphology to a dendritic structure as
      growth proceeds. Correspondingly, the surface composition becomes nonuniform and
      the fractal dimension associated with the islands evolves from 2.0 to a stable
      value of 1.87, indicating a transition in the rate-limiting mechanism of
      oxidation from oxygen surface diffusion to diffusion of copper through the
      increasingly gold-rich regions adjacent to the islands.

PMID- 16803331
TI  - Local atomic structure and discommensurations in the charge density wave of
      CeTe3.
AB  - The local structure of in the incommensurate charge density wave (IC-CDW) state
      has been obtained using atomic pair distribution function analysis of x-ray
      diffraction data. Local atomic distortions in the Te nets due to the CDW are
      larger than observed crystallographically, resulting in distinct short and long
      Te-Te bonds. Observation of different distortion amplitudes in the local and
      average structures is explained by the discommensurated nature of the CDW, since
      the pair distribution function is sensitive to the local displacements within the
      commensurate regions, whereas the crystallographic result averages over many
      discommensurated domains. The result is supported by STM data. This is the first
      quantitative local structural study within the commensurate domains in an IC-CDW
      system.

PMID- 16803332
TI  - Quasiparticle self-consistent GW theory.
AB  - In past decades the scientific community has been looking for a reliable first
      principles method to predict the electronic structure of solids with high
      accuracy. Here we present an approach which we call the quasiparticle self
      consistent approximation. It is based on a kind of self-consistent perturbation
      theory, where the self-consistency is constructed to minimize the perturbation.
      We apply it to selections from different classes of materials, including alkali
      metals, semiconductors, wide band gap insulators, transition metals, transition
      metal oxides, magnetic insulators, and rare earth compounds. Apart from some mild
      exceptions, the properties are very well described, particularly in weakly
      correlated cases. Self-consistency dramatically improves agreement with
      experiment, and is sometimes essential. Discrepancies with experiment are
      systematic, and can be explained in terms of approximations made.

PMID- 16803333
TI  - Local self-energy approach for electronic structure calculations.
AB  - Using a novel self-consistent implementation of Hedin's perturbation theory, we
      calculate space- and energy-dependent self-energy for a number of materials. We
      find it to be local in real space and rapidly convergent on second- to third
      nearest neighbors. Corrections beyond are evaluated and shown to be completely
      localized within a single unit cell. This can be viewed as a fully self
      consistent implementation of the dynamical mean field theory for electronic
      structure calculations of real solids using a perturbative impurity solver.

PMID- 16803334
TI  - Universal dephasing rate due to diluted Kondo impurities.
AB  - We calculate the dephasing rate due to magnetic impurities in a weakly disordered
      metal as measured in a weak-localization experiment. If the density nS of
      magnetic impurities is sufficiently low, the dephasing rate 1/tauphi is a
      universal function, 1/tauphi=(nS/nu)f(T/TK), where TK is the Kondo temperature
      and nu is the density of states. We show that inelastic vertex corrections with a
      typical energy transfer DeltaE are suppressed by powers of 1/(tauphiDeltaE)
      proportional to nS. Therefore, the dephasing rate can be calculated from the
      inelastic cross section proportional to pinu ImT-/pinuT/2, where T is the T
      matrix which is evaluated numerically exactly using the numerical renormalization
      group.

PMID- 16803335
TI  - Physical picture behind the oscillating sign of drag in high Landau levels.
AB  - We consider the oscillating sign of the drag resistivity and its anomalous
      temperature dependence discovered experimentally in a bilayer system in the
      regime of the integer quantum Hall effect. We attribute the oscillating sign to
      the effect of disorder on the relation between an adiabatic momentum transfer to
      an electron and the displacement of its position. While in the absence of any
      Landau level mixing a momentum transfer implies a displacement of (with being the
      magnetic length), Landau level mixing induced by short range disorder adds a
      potentially large displacement that depends on the electron's energy, with the
      sign being odd with respect to the distance of that energy from the center of the
      Landau level. We show how the oscillating sign of drag disappears when the
      disorder is smooth and when the electronic states are localized.

PMID- 16803336
TI  - Self-purification in semiconductor nanocrystals.
AB  - Doping of nanocrystals is an important and very difficult task. "Self
      purification" mechanisms are often claimed to make this task even more difficult,
      as the distance a defect or impurity must move to reach the surface of a
      nanocrystal is very small. We show that self-purification can be explained
      through energetic arguments and is an intrinsic property of defects in
      semiconductor nanocrystals. We find the formation energies of defects increases
      as the size of the nanocrystal decreases. We analyze the case of Mn-doped CdSe
      nanocrystals and compare our results to experimental findings.

PMID- 16803337
TI  - Switching noise as a probe of statistics in the fractional quantum Hall effect.
AB  - We propose an experiment to probe the unconventional quantum statistics of
      quasiparticles in fractional quantum Hall states by measurement of current noise.
      The geometry we consider is that of a Hall bar where two quantum point contacts
      introduce two interfering amplitudes for backscattering. Thermal fluctuations of
      the number of quasiparticles enclosed between the two point contacts introduce
      current noise, which reflects the statistics of the quasiparticles. We analyze
      Abelian nu=1/q states and the non-Abelian nu=5/2 state.

PMID- 16803338
TI  - Coexistence of f-wave superconductivity, charge order, and spin
      antiferromagnetism around nonmagnetic impurities in Na0.33CoO2.1.3H2O.
AB  - To check whether charge dynamics is responsible for the superconductivity in
      NaxCoO2.yH2O, we investigate local electronic and magnetic structure around
      nonmagnetic impurities embedded in this material at x=0.33 in the vicinity of
      charge instability, by using a phenomenological model within the slave-boson
      framework including competitions among a square root of 3 x square root of 3
      charge order, antiferromagnetism, and f-wave superconductivity. Around the
      repulsive impurities, it is found that both local charge and spin orders are
      induced. Furthermore, the f-wave pairing order parameter is decreased on one
      sublattice but increased on another honeycomb sublattice. If the charge dynamics
      is responsible for the superconductivity, the predicted local electronic and
      magnetic structure could be observed by the STM and spatial resolved NMR
      experiments.

PMID- 16803339
TI  - Electrostatic modulation of the superfluid density in an ultrathin film.
AB  - By capacitively charging an underdoped ultrathin La2-xSrxCuO4 film with an
      electric field applied across a gate insulator with a high dielectric constant,
      relative changes of the areal superfluid density ns of unprecedented strength
      were observed in measurements of the film kinetic inductance. Although ns appears
      to be substantially reduced by disorder, the data provide, for the first time on
      the same sample, direct compelling evidence for the Uemura relation Tc
      proportional to ns(T=0) in the underdoped regime of copper-oxide superconductors.

PMID- 16803340
TI  - Strong-disorder fixed point in the dissipative random transverse-field Ising
      model.
AB  - The interplay between disorder, quantum fluctuations, and dissipation is studied
      in the random transverse Ising chain coupled to a dissipative Ohmic bath with a
      real space renormalization group. A typically very large length scale L* is
      identified above which the physics of frozen clusters dominates. Below L* a
      strong-disorder fixed point determines scaling at a pseudocritical point. In a
      Griffiths-McCoy region frozen clusters produce already a finite magnetization
      resulting in a classical low temperature behavior of the susceptibility and
      specific heat. These override the confluent singularities that are characterized
      by a continuously varying exponent z and are visible above a temperature
      T*approximately L*-z.

PMID- 16803341
TI  - Random generation of coherent solitary waves from incoherent waves.
AB  - The random generation of coherent solitary waves from incoherent waves in a
      medium with an instantaneous nonlinearity has been observed. One excites a
      propagating incoherent spin wave packet in a magnetic film strip and observes the
      random appearance of solitary wave pulses. These pulses are as coherent as
      traditional solitary waves, but with random timing and a random peak amplitude.

PMID- 16803342
TI  - Optical control of spin coherence in singly charged (In,Ga)As/GaAs quantum dots.
AB  - Electron spin coherence has been generated optically in n-type modulation doped
      (In,Ga)As/GaAs quantum dots (QDs) which contain on average a single electron per
      dot. The coherence arises from resonant excitation of the QDs by circularly
      polarized laser pulses, creating a coherent superposition of an electron and a
      trion. Time dependent Faraday rotation is used to probe the spin precession of
      the optically oriented electrons about a transverse magnetic field. The coherence
      generation can be controlled by pulse intensity, being most efficient for
      (2n+1)pi pulses.

PMID- 16803343
TI  - Trapping of cold excitons in quantum well structures with laser light.
AB  - Optical trapping and manipulation of neutral particles has led to a variety of
      experiments from stretching DNA-molecules to trapping and cooling of neutral
      atoms. An exciting recent outgrowth of the technique is an experimental
      implementation of atom Bose-Einstein condensation. In this Letter, we propose and
      demonstrate laser-induced trapping for a new system--a gas of excitons in quantum
      well structures. We report on the trapping of a highly degenerate Bose gas of
      excitons in laser-induced traps.

PMID- 16803344
TI  - Spin-transfer-driven ferromagnetic resonance of individual nanomagnets.
AB  - We demonstrate a technique that enables ferromagnetic resonance measurements of
      the normal modes for magnetic excitations in individual nanoscale ferromagnets,
      smaller in volume by more than a factor of 50 compared to individual
      ferromagnetic samples measured by other resonance techniques. Studies of the
      resonance frequencies, amplitudes, linewidths, and line shapes as a function of
      microwave power, dc current, and magnetic field provide detailed new information
      about the exchange, damping, and spin-transfer torques that govern the dynamics
      in magnetic nanostructures.

PMID- 16803345
TI  - Perfect softening of the ferroelectric mode in the isotope-exchanged strontium
      titanate of SrTi18O3 studied by light scattering.
AB  - The mode of the isotope-induced ferroelectric strontium titanate shows a perfect
      softening at the ferroelectric phase transition temperature , where the frequency
      of the underdamped mode approaches completely to zero within the instrumental
      resolution. The spectra of the Raman inactive soft mode have been successfully
      observed owing to local symmetry breaking and by long-term accumulation of the
      spectral intensity with a high resolution technique. The mechanism of the phase
      transition is concluded to be an ideal displacive-type accompanied with perfect
      softening of the Slater-type polar mode. The difference between the soft mode
      behavior of and indicates that the origin of the quantum paraelectric state of
      lies in the quantum fluctuation of the oxide octahedron in the perovskite
      structure.

PMID- 16803346
TI  - Freezing of random RNA.
AB  - We study secondary structures of random RNA molecules by means of a renormalized
      field theory based on an expansion in the sequence disorder. We show that there
      is a continuous phase transition from a molten phase at higher temperatures to a
      low-temperature glass phase. The primary freezing occurs above the critical
      temperature, with local islands of stable folds forming within the molten phase.
      The size of these islands defines the correlation length of the transition. Our
      results include critical exponents at the transition and in the glass phase.

PMID- 16803347
TI  - Nyquist noise of cell adhesion detected in a neuron-silicon transistor.
AB  - Interfacing of nerve cells and field-effect transistors is determined by current
      flow along the electrical resistance of the cell-chip junction. We study the
      thermal noise of the junction by measuring the fluctuations of extracellular
      voltage with a low-noise transistor. We find a spectral power density of 5 x 10(
      14) V2/Hz and interpret it as Nyquist noise of the cell-chip junction with a
      resistance of 3 MOhm. The thermal noise allows us to elucidate the properties of
      cell adhesion and it sets a thermodynamical limit for the signal-to-noise ratio
      of neuroelectronic interfacing.

PMID- 16803348
TI  - Lateral diffusion and percolation in membranes.
AB  - An algorithm based on Voronoi tessellation and percolation theory is presented to
      study the diffusion of model membrane components (solutes) in the plasma
      membrane. The membrane is modeled as a two-dimensional space with integral
      membrane proteins as static obstacles. The Voronoi diagram consists of vertices,
      which are equidistant from three matrix obstacles, joined by edges. An edge
      between two vertices is said to be connected if solute particles can pass
      directly between the two regions. The percolation threshold, pc, determined using
      this passage criterion is pc approximately equal to 0.53. This is smaller than if
      the connectivity of edges were assigned randomly, in which case the percolation
      threshold pr=2/3, where p is the fraction of connected edges. Molecular dynamics
      simulations show that diffusion is determined by percolation of clusters of
      edges.

PMID- 16803349
TI  - Diffusive model of protein folding dynamics with Kramers turnover in rate.
AB  - We study the folding kinetics of a three-helix bundle protein using a coarse
      polymer model. The folding dynamics can be accurately represented by one
      dimensional diffusion along a reaction coordinate selected to capture the
      transition state. By varying the solvent friction, we show that position
      dependent diffusion coefficients are determined by microscopic transitions on a
      rough energy landscape. A maximum in the folding rate at intermediate friction is
      explained by "Kramers turnover" in these microscopic dynamics that modulates the
      rate via the diffusion coefficient; overall folding remains diffusive even close
      to zero friction. For water friction, we find that the "attempt frequency" (or
      "speed limit") in a Kramers model of folding is about 2 micros-1, with an
      activation barrier of about 2kBT, and a folding transition path duration of
      approximately equal to 100 ns, 2 orders of magnitude less than the folding time
      of approximately equal to 10 micros.

PMID- 16803350
TI  - How long does it take to pull an ideal polymer into a small hole?
AB  - We present scaling estimates for characteristic times taulin and taubr of pulling
      ideal linear and randomly branched polymers of N monomers into a small hole by a
      force f. We show that the absorbtion process develops as sequential straightening
      of folds of the initial polymer configuration. By estimating the typical size of
      the fold involved into the motion, we arrive at the following predictions,
      taulin(N) approximately N3/2/f and taubr(N)approximately N5/4/f, and we also
      confirm them by the molecular dynamics experiment.

PMID- 16803351
TI  - Microscopic dynamics of recovery in sheared depletion gels.
AB  - We report x-ray photon correlation spectroscopy and diffusing wave spectroscopy
      studies of depletion gels formed from nanoscale silica colloids in solutions of
      nonabsorbing polymer following the cessation of shear. The two techniques provide
      a quantitatively coherent picture of the dynamics as ballistic or convective
      motion of colloidal clusters whose internal motion is arrested. While the
      dynamics possesses features characteristic of nonergodic soft solids, including a
      relaxation time that grows linearly with the time since shear, comparison with
      behavior of quenched supercooled liquids indicates that this evolution is not
      directly related to traditional aging phenomena in glasses.

PMID- 16803352
TI  - Positronium formed by recombination of positron-electron pairs in polymers.
AB  - In nonpolar polymers, positronium (Ps) is dominantly formed by fast intraspur
      reactions of the energetic positron, but its formation is partially contributed
      by recombination of weakly bound Mott-Wannier-like positron-electron pairs and is
      susceptible to electric field and positron irradiation induced perturbations. The
      average initial energy of para-Ps (p-Ps) formed by recombination is found to be
      about half the energy of ordinary p-Ps dominantly formed by the fast intraspur
      reactions.

PMID- 16803354
TI  - Biased tomography schemes: an objective approach.
AB  - We report on an intrinsic relationship between the maximum-likelihood quantum
      state estimation and the representation of the signal. A quantum analogy of the
      transfer function determines the space where the reconstruction should be done
      without the need for any ad hoc truncations of the Hilbert space. An illustration
      of this method is provided by a simple yet practically important tomography of an
      optical signal registered by realistic binary detectors.

PMID- 16803353
TI  - Single molecular anatomy of solvophobic effects in host-guest interactions based
      on surface tension using atomic force microscopy.
AB  - The effectiveness of the mechanism of surface tension to analyze the host-guest
      interaction was demonstrated by measuring the unbinding force of the beta
      Cyclodextrin (CyD)--adamantane molecules in a liquid environment at the single
      molecule level. The contribution of the solvophobic effect was quantitatively
      distinguished from the intrinsic van der Waals force, and the effective length
      that produces the detected force through employing the notion of surface tension
      was determined to be , which is consistent with the perimeter of the adamantane
      molecule, . Specific strong interaction of water molecules was also confirmed on
      the nanoscale.

PMID- 16803355
TI  - Vortex-lattice melting in a one-dimensional optical lattice.
AB  - We investigate quantum fluctuations of a vortex lattice in a one-dimensional
      optical lattice for realistic numbers of particles and vortices. Our method gives
      full access to all the modes of the vortex lattice and we discuss in particular
      the Bloch bands of the Tkachenko modes. Because of the small number of particles
      in the pancake Bose-Einstein condensates at every site of the optical lattice,
      finite-size effects become very important. Therefore, the fluctuations in the
      vortex positions are inhomogeneous and the melting of the lattice occurs from the
      outside inwards. By looking into correlations between neighboring vortices, we
      identify new solid and liquid phases. Tunneling between neighboring pancakes
      substantially reduces the inhomogeneity as well as the size of the fluctuations.

PMID- 16803356
TI  - Synchronization in the BCS pairing dynamics as a critical phenomenon.
AB  - Fermi gas with time-dependent pairing interaction hosts several different
      dynamical states. Coupling between the collective BCS pairing mode and individual
      Cooper pair states can make the latter either synchronize or dephase. We describe
      transition from phase-locked undamped oscillations to Landau-damped dephased
      oscillations in the collisionless, dissipationless regime as a function of
      coupling strength. In the dephased regime, we find a second transition at which
      the long-time asymptotic pairing amplitude vanishes. Using a combination of
      numerical and analytical methods we establish a continuous (type II) character of
      both transitions.

PMID- 16803357
TI  - Dynamical vanishing of the order parameter in a fermionic condensate.
AB  - We analyze the dynamics of a condensate of ultracold atomic fermions following an
      abrupt change of the pairing strength. At long times, the system goes to a
      nonstationary steady state, which we determine exactly. The superfluid order
      parameter asymptotes to a constant value. We show that the order parameter
      vanishes when the pairing strength is decreased below a certain critical value.
      In this case, the steady state of the system combines properties of normal and
      superfluid states -- the gap and the condensate fraction vanish, while the
      superfluid density is nonzero.

PMID- 16803358
TI  - Entanglement of two impurities through electron scattering.
AB  - We study how two magnetic impurities embedded in a solid can be entangled by an
      injected electron scattering between them and by subsequent measurement of the
      electron's state. We start by investigating an ideal case where only the
      electronic spin interacts successively through the same unitary operation with
      the spins of the two impurities. We find conditions for the impurity spins to be
      maximally entangled with a significant success probability. We then consider a
      more realistic description which includes both the forward and backscattering
      amplitudes. In this scenario, we obtain the entanglement between the impurities
      as a function of the interaction strength of the electron-impurity coupling. We
      find that our scheme allows us to entangle the impurities maximally with a
      significant probability.

PMID- 16803359
TI  - Decoherence in a system of many two-level atoms.
AB  - I show that the decoherence in a system of degenerate two-level atoms interacting
      with a bosonic heat bath is for any number of atoms governed by a generalized
      Hamming distance (called "decoherence metric") between the superposed quantum
      states, with a time-dependent metric tensor that is specific for the heat bath.
      The decoherence metric allows for the complete characterization of the
      decoherence of all possible superpositions of many-particle states, and can be
      applied to minimize the overall decoherence in a quantum memory. For qubits which
      are far apart, the decoherence is given by a function describing single-qubit
      decoherence times the standard Hamming distance. I apply the theory to cold atoms
      in an optical lattice interacting with blackbody radiation.

PMID- 16803360
TI  - Anomalous diffusion of inertial, weakly damped particles.
AB  - The anomalous (i.e., non-Gaussian) dynamics of particles subject to a
      deterministic acceleration and a series of "random kicks" is studied. Based on an
      extension of the concept of continuous time random walks to position-velocity
      space, a new fractional equation of the Kramers-Fokker-Planck type is derived.
      The associated collision operator necessarily involves a fractional substantial
      derivative, representing important nonlocal couplings in time and space. For the
      force-free case, a closed solution is found and discussed.

PMID- 16803361
TI  - Nonequilibrium quantum condensation in an incoherently pumped dissipative system.
AB  - We study spontaneous quantum coherence in an out of an equilibrium system,
      coupled to multiple baths describing pumping and decay. For a range of parameters
      describing coupling to, and occupation of the baths, a stable steady-state
      condensed solution exists. The presence of pumping and decay significantly
      modifies the spectra of phase fluctuations, leading to correlation functions that
      differ both from an isolated condensate and from a laser.

PMID- 16803362
TI  - Simulating nanoscale dielectric response.
AB  - We introduce a constrained energy functional to describe dielectric response. We
      demonstrate that the local functional is a generalization of the long-ranged
      Marcus energy. Our reformulation is used to implement a cluster Monte Carlo
      algorithm for the simulation of dielectric media. The algorithm avoids solving
      the Poisson equation and remains efficient in the presence of spatial
      heterogeneity, nonlinearity, and scale dependent dielectric properties.

PMID- 16803363
TI  - Enhanced sensitivity to fundamental constants in ultracold atomic and molecular
      systems near Feshbach resonances.
AB  - Scattering length, which can be measured in Bose-Einstein condensate and Feshbach
      molecule experiments, is extremely sensitive to the variation of fundamental
      constants, in particular, the electron-to-proton mass ratio (m(e)/m(p) or
      m(e)/Lambda(QCD), where Lambda(QCD), is the QCD scale). Based on single- and two
      channel scattering models, we show how the variation of the mass ratio propagates
      to the scattering length. Our results suggest that variation of m(e)/m(p) on the
      level of 10(-11) - 10(-14) on the level of can be detected near a narrow magnetic
      or an optical Feshbach resonance by monitoring the scattering length on the 1%
      level. Derived formulas may also be used to estimate the isotopic shift of the
      scattering length.

PMID- 16803364
TI  - Compensation of strong thermal lensing in high-optical-power cavities.
AB  - In an experiment to simulate the conditions in high optical power advanced
      gravitational wave detectors, we show for the first time that the time evolution
      of strong thermal lenses follows the predicted infinite sum of exponentials
      (approximated by a double exponential), and that such lenses can be compensated
      using an intracavity compensation plate heated on its cylindrical surface. We
      show that high finesse approximately 1400 can be achieved in cavities with
      internal compensation plates, and that mode matching can be maintained. The
      experiment achieves a wave front distortion similar to that expected for the
      input test mass substrate in the Advanced Laser Interferometer Gravitational Wave
      Observatory, and shows that thermal compensation schemes are viable. It is also
      shown that the measurements allow a direct measurement of substrate optical
      absorption in the test mass and the compensation plate.

PMID- 16803365
TI  - Displacement- and timing-noise-free gravitational-wave detection.
AB  - Motivated by a recently invented scheme of displacement-noise-free gravitational
      wave detection, we demonstrate the existence of gravitational-wave detection
      schemes insusceptible to both displacement and timing (laser) noises and are thus
      realizable by shot-noise-limited laser interferometry. This is possible due to
      two reasons: first, gravitational waves and displacement disturbances contribute
      to light propagation times in different manners; second, for an N-detector
      system, the number of signal channels is of the order Omicron(N(2)), while the
      total number of timing- and displacement-noise channels is of the order
      Omicron(N).

PMID- 16803366
TI  - Nonlinear perturbations of the Kaluza-Klein monopole.
AB  - We consider the nonlinear stability of the Kaluza-Klein monopole viewed as the
      static solution of the five-dimensional vacuum Einstein equations. Using both
      numerical and analytical methods, we give evidence that the Kaluza-Klein monopole
      is asymptotically stable within the cohomogeneity-two biaxial Bianchi type-IX
      ansatz recently introduced by Bizon, Chmaj, and Schmidt. We also show that for
      sufficiently large perturbations the Kaluza-Klein monopole loses stability and
      collapses to a Kaluza-Klein black hole. The relevance of our results for the
      stability of Bogomol'nyi-Prasad-Sommerfield states in M or string theory is
      briefly discussed.

PMID- 16803367
TI  - Gravitational correction to running of gauge couplings.
AB  - We calculate the contribution of graviton exchange to the running of gauge
      couplings at lowest non-trivial order in perturbation theory. Including this
      contribution in a theory that features coupling constant unification does not
      upset this unification, but rather shifts the unification scale. When
      extrapolated formally, the gravitational correction renders all gauge couplings
      asymptotically free.

PMID- 16803369
TI  - Natural electroweak breaking from a mirror symmetry.
AB  - We present "twin Higgs models," simple realizations of the Higgs boson as a
      pseudo Goldstone boson that protect the weak scale from radiative corrections up
      to scales of order 5-10 TeV. In the ultraviolet these theories have a discrete
      symmetry which interchanges each standard model particle with a corresponding
      particle which transforms under a twin or a mirror standard model gauge group. In
      addition, the Higgs sector respects an approximate global symmetry. When this
      global symmetry is broken, the discrete symmetry tightly constrains the form of
      corrections to the pseudo Goldstone Higgs potential, allowing natural electroweak
      symmetry breaking. Precision electroweak constraints are satisfied by
      construction. These models demonstrate that, contrary to the conventional wisdom,
      stabilizing the weak scale does not require new light particles charged under the
      standard model gauge groups.

PMID- 16803370
TI  - W Boson production cross section at the Large Hadron cCllider with
      Omicron(alpha(2)(s)) corrections.
AB  - We compute the Omicron(alpha(2)(s)) QCD corrections to the fully differential
      cross section pp --> WX --> lnuX, retaining all effects from spin correlations.
      The knowledge of these corrections makes it possible to calculate with high
      precision the boson production rate and acceptance at the CERN Large Hadron
      Collider (LHC), subject to realistic cuts on the lepton and missing energy
      distributions. For certain choices of cuts we find large corrections when going
      from next-to-leading order (NLO) to next-to-next-to-leading order in perturbation
      theory. These corrections are significantly larger than those obtained by parton
      shower event generators merged with NLO calculations. Our result may be used to
      assess and significantly reduce the QCD uncertainties in the many studies of
      boson production planned at the LHC.

PMID- 16803373
TI  - How low-energy weak reactions can constrain three-nucleon forces and the neutron
      neutron scattering length.
AB  - We show that chiral symmetry and gauge invariance enforce relations between the
      short-distance physics that occurs in a number of electroweak and pionic
      reactions on light nuclei. Within chiral perturbation theory, this is manifested
      via the appearance of the same axial isovector two-body contact term in pi(-)d -
      > nngamma, p-wave pion production in NN collisions, tritium beta decay, pp
      fusion, nud scattering, and the hep reaction. Using a Gamow-Teller matrix element
      obtained from calculations of pp fusion as input, we compute the neutron spectrum
      obtained in pi(-)d --> nngamma. With the short-distance physics in this process
      controlled from pp --> de(=)nu(e), the theoretical uncertainty in the nn
      scattering length extracted from pi(-)d --> nngamma is reduced by a factor larger
      than 3, to approximately < or = 0.05 fm.

PMID- 16803372
TI  - Measurement of azimuthal asymmetries in inclusive production of hadron pairs in
      e(+)e(-) annihilation at Belle.
AB  - The Collins effect connects transverse quark spin with a measurable azimuthal
      dependence in the yield of hadronic fragments around the quark's momentum vector.
      Using two different reconstruction methods, we find evidence of statistically
      significant azimuthal asymmetries for charged pion pairs in e(+)e(-) annihilation
      at a center-of-mass energy of 10.52 GeV, which can be attributed to a transverse
      polarization of the primordial quarks. The measurement was performed using a
      sample of 79 x 10(6) hadronic events collected with the Belle detector.

PMID- 16803375
TI  - Coincidence and total photoelectron spectra and their differences induced by
      internal degrees of freedom.
AB  - Recent progress in experimental techniques have made it possible to measure
      photoelectron spectra in coincidence with particles emitted during the decay of
      the photoionized species. In this work it will be shown that, contrary to
      intuition, these coincident photoelectron spectra can be qualitatively different
      from the photoelectron spectra resulting when all photoelectrons are detected. In
      particular they carry information on the decay mechanism following
      photoionization as soon as the decay is influenced by internal degrees of freedom
      of the photoionized system. This is shown explicitly for the case of vibrational
      degrees of freedom of molecules and demonstrated with a model study.

PMID- 16803374
TI  - Enhanced core polarization in (70)Ni and (74)Zn.
AB  - The reduced transition probabilities B(E2;0(+) --> 2(+)(1)) of the neutron-rich
      (74)Zn and (70)Ni nuclei have been measured by Coulomb excitation in a (208)Pb
      target at intermediate energy. These nuclei have been produced at Grand
      Accelerateur National d'Ions Lourds via interactions of a 60A MeV (76)Ge beam
      with a Be target. The B(E2) value for (70)Ni(42) is unexpectedly large, which
      indicates that neutrons added above N=40 strongly polarize the Z=28 proton core.
      In the Zn isotopic chain, the steep rise of B(E2) values beyond N=40 continues up
      to (74)Zn(44). The enhanced proton core polarization in (70)Ni is attributed to
      the monopole interaction between the neutron in the g(9/2) and protons in the
      f(7/2) and f(5/2) spin-orbit partner orbitals. This interaction could result in a
      weakening of magicity in (78)Ni(50).

PMID- 16803376
TI  - Convergence of experiment and theory on the pure vibrational spectrum of HeH(+).
AB  - Very accurate quantum mechanical calculations of the pure vibrational spectrum of
      the molecular ion are reported and compared with newly obtained pure vibrational
      transitions extracted from the available experimental data. The calculations are
      performed without assuming the Born-Oppenheimer approximation regarding
      separability of the nuclear and electronic motions and include the first order
      relativistic mass-velocity and Darwin corrections. For the two lowest
      transitions, whose experimental energies are established with the highest
      precision, the calculated and the experimental results show very good agreement.

PMID- 16803377
TI  - Young-type interference in (e, 2e) ionization of H(2).
AB  - We have investigated the electron impact single ionization of the hydrogen
      molecule, with fully determined kinematics. The experimental and theoretical
      results are compared with He ionization under the same conditions. The results
      indicate that the ejected electron angular distribution for H(2) is modified due
      to Young-type interference between ionization amplitudes for scattering from the
      two centers in the hydrogen molecule. The observable result is a suppression of
      the backward scattering (recoil) peak compared with the binary peak.

PMID- 16803378
TI  - Isomorphous substitution in bimetallic oxide clusters.
AB  - The geometric and electronic structure of bimetallic oxide clusters is studied as
      a function of their composition with gas phase vibrational spectroscopy. Infrared
      multiple photon dissociation spectra of titanium-vanadium oxide cluster anions
      are measured in the 500 to 1200 wave number range and assigned on the basis of
      harmonic frequencies calculated using density functional theory. Singly
      substituted (V(2)O(5))(n-1)(VTiO(5))(-) (n=2-4) cluster anions are shown to form
      polyhedral caged structures similar to those predicted for their isoelectronic
      counterparts, the neutral (V(2)O(5))(n) clusters. Upon systematic exchange of V
      by Ti atoms in V(4-n)Ti(n)O(-)(10) (n=1-4), the structure does not change. The
      stress induced by the isomorphous substitution results in an increased number of
      unpaired electrons (n-1) for the Ti-rich systems, leading to a quartet ground
      state for Ti(4)O(-)(10).

PMID- 16803368
TI  - Observation of B(0)(s)-->Psi(2S)Phi and measurement of the ratio of branching
      fractions Beta(B(0)(s)-->Psi(2S)Phi)/Beta(B(0)(s)-->J/PsiPhi).
AB  - We report the first observation of B(0)(s)-->Psi(2S)Phi decay in p(p_) collisions
      at square root of 8=1.96 TeV using 360 pb(-1) of data collected by the CDF II
      detector at the Fermilab Tevatron. We observe 20.2 +/- 5.0 and 12.3 +/- 4.1
      B(0)(s)-->Psi(2S)Phi candidates, in Psi(2S)-->mu(+)mu(-) and Phi(2S)-
      >J/Phipi(+)pi(-) decay modes, respectively. We present a measurement of the
      relative branching fraction Beta(B(0)(s)-->Psi(2S)Phi)/Beta(B(0)(s)-
      >J/PsiPhi)=0.52 +/- 0.13(stat) +/- 0.04(syst) +/- 0.06(BR) using the Psi(2S)-
      >mu(+)mu(-) decay mode.

PMID- 16803379
TI  - Enhanced transmission through periodic arrays of subwavelength holes: the role of
      localized waveguide resonances.
AB  - By using the rigid full-vectorial three-dimensional finite-difference time-domain
      method, we show that the enhanced transmission through a metallic film with a
      periodic array of subwavelength holes results from two different resonances: (i)
      localized waveguide resonances where each air hole can be considered as a section
      of metallic waveguide with both ends open to free space, forming a low-quality
      factor resonator, and (ii) well-recognized surface plasmon resonances due to the
      periodicity. These two different resonances can be characterized from
      electromagnetic band structures in the structured metal film. In addition, we
      show that the shape effect in the enhanced transmission through the Au film with
      subwavelength holes is attributed to the localized waveguide resonance.

PMID- 16803380
TI  - Parametric amplification of the dynamic radiation force of acoustic waves in
      fluids.
AB  - We report on parametric amplification in dynamic radiation force produced by a
      bichromatic acoustic beam in a fluid. To explain this effect we develop a theory
      taking into account the nonlinearity of the fluid. The theory is validated
      through an experiment to measure the dynamic radiation force on an acrylic
      sphere. Results exhibit an amplification of 66 dB in water and 80 dB in alcohol
      as the difference of the frequencies is increased from 10 Hz to 240 kHz.

PMID- 16803381
TI  - Evidence of the presence of opticlike collective modes in a liquid from neutron
      scattering experiments.
AB  - Inelastic neutron scattering data from liquid DF close to the melting point show,
      in addition to spectra comprising quasielastic and heavily damped acoustic
      motions, an intense, nondispersive band centered at about 27 meV along with a
      broader higher energy feature. Observation of the former band provides the first
      direct verification of the existence within the liquid state of collective
      opticlike excitations as predicted by molecular dynamics simulations. The latter
      corresponds to mainly reorientational motions assigned from mode eigenvector
      analysis carried out by computer simulations.

PMID- 16803382
TI  - Glass fragility and atomic ordering on the intermediate and extended range.
AB  - The relation between the fragility of glass-forming systems, a parameter which
      describes many of their key physical characteristics, and atomic scale structure
      is investigated by using neutron diffraction to measure the topological and
      chemical ordering for germania, or GeO(2), which is an archetypal strong glass
      former. We find that the ordering for this and other tetrahedral network-forming
      glasses at distances greater than the nearest neighbor can be rationalized in
      terms of an interplay between the relative importance of two length scales. One
      of these is associated with an intermediate range, the other with an extended
      range and, with increasing glass fragility, it is the extended range ordering
      which dominates.

PMID- 16803383
TI  - Glasslike two-level systems in minimally disordered mixed crystals.
AB  - THz spectroscopy is used to identify a broad distribution of two-level systems,
      characteristic of glasses, in the substitutional monatomic mixed crystal systems,
      Ba(1-x)Ca(x)F(2) and Pb(1-x)Ca(x)F(2). In these minimally disordered systems, two
      level behavior, which was not previously known to occur, begins at a specific
      CaF(2) concentration. The concentration dependence, successfully modeled using
      the statistics of the impurity distribution in the lattice, points to a
      collective dopant tunneling mechanism.

PMID- 16803384
TI  - Aging dynamics and the topology of inhomogenous networks.
AB  - We study phase ordering on networks and we establish a relation between the
      exponent a(x) of the aging part of the integrated auto-response function and the
      topology of the underlying structures. We show that a(x) > 0 in full generality
      on networks which are above the lower critical dimension d(L), i.e., where the
      corresponding statistical model has a phase transition at finite temperature. For
      discrete symmetry models on finite ramified structures with T(c) = 0, which are
      at the lower critical dimension d(L), we show that a(x) is expected to vanish. We
      provide numerical results for the physically interesting case of the 2 - d
      percolation cluster at or above the percolation threshold, i.e., at or above
      d(L), and for other networks, showing that the value of a(x) changes according to
      our hypothesis. For O(N) models we find that the same picture holds in the large
      N limit and that a(x) only depends on the spectral dimension of the network.

PMID- 16803385
TI  - Chaos and residual correlations in pinned disordered systems.
AB  - We study, using functional renormalization, two copies of an elastic system
      pinned by mutually correlated random potentials. Short scale decorrelation
      depends on a nontrivial boundary layer regime with (possibly multiple) chaos
      exponents. Large scale mutual displacement correlations behave as [x - x'](2zeta
      mu), mu proportional to the difference between Flory (or mean field) and exact
      roughness exponents zeta. For short range disorder mu>0 and small; e.g., for
      random bond interfaces mu=5zeta-epsilon, epsilon=4-d, and
      mu=epsilon{[(2pi)(2)/36]-1} for the one component Bragg glass. Random field
      (i.e., long range) disorder exhibits finite residual correlations (no chaos mu=0)
      described by new functional renormalization fixed points. Temperature and dynamic
      chaos (depinning) are discussed.

PMID- 16803386
TI  - Influence of the angular distribution function of incident particles on the
      microstructure and anomalous scaling behavior of thin films.
AB  - The microstructure and the scaling properties of films grown by plasma enhanced
      chemical vapor deposition are reproduced with a discrete model that takes into
      account the angular distribution function of the particles and the lateral growth
      of the films. Both the experimental and simulated surfaces exhibit a granular
      microstructure and an anomalous scaling behavior characterized by values of the
      growth exponent beta that vary with the scale of measurement. Depending on the
      angular distribution function used in the model, values of beta ranging from 0.86
      to 0.2 are obtained.

PMID- 16803387
TI  - Velocity dependence of friction and hydrogen bonding effects.
AB  - We show that the friction force varies with the sliding velocity in a manner that
      depends on the chemical nature of the interface. Surfaces terminated with the
      hydrogen acceptor and donor moieties capable of forming H-bond networks exhibit a
      friction that decreases with sliding velocity, a behavior that is opposite to
      that of surfaces where no such networks can form. We explain the results with a
      model where the domains of glassy H-bond networks are disrupted at a critical
      applied stress leading to slippage.

PMID- 16803371
TI  - Observation of Upsilon(4S) decays to pi(+)pi(-)Upsilon(1S) and pi(+)pi(
      )Upsilon(2S).
AB  - Observation of Upsilon(4S) decays to pi(+)pi(-)C and pi(+)pi(-)Upsilon(2S)We
      present the first measurement of Upsilon(4S) decays to pi(+)pi(-)Upsilon(1S)
      based on a sample of 230 x 106(4S) mesons collected with the BABAR detector. We
      measure the product branching fractions Beta(Upsilon(4S) --> pi(+)pi(
      )Upsilon(1S)) x BetaUpsilon(1S) --> mu(+)mu(-) = (2.23 +/- 0.25(stat) +/-
      0.27(syst))x 10(-6) and Beta(Upsilon(4S) --> pi(+)pi(-)Upsilon(2S) x
      Beta(Upsilon(2S) --> mu(+)mu(-))=(1.69 +/-0.26(stat) +/- 0.20(syst)) x 10(-)6,
      from which we derive the partial widths Gamma(Upsilon(4S) --> pi(+)pi(
      )Upsilon(1S))=(1.8 +/-0.4) keV and Gamma(Upsilon(4S) --> pi(+)pi(
      )Upsilon(2S))=(2.7 +/- 0.8) keV.

PMID- 16803388
TI  - Valley polarization in Si(100) at zero magnetic field.
AB  - The valley splitting, which lifts the degeneracy of the lowest two valley states
      in a SiO(2)/Si(100)/SiO(2) quantum well, is examined through transport
      measurements. We demonstrate that the valley splitting can be observed directly
      as a step in the conductance defining a boundary between valley-unpolarized and 
      polarized regions. This persists to well above liquid helium temperature and
      shows no dependence on magnetic field, indicating that single-particle valley
      splitting and valley polarization exist in (100) silicon even at zero magnetic
      field.

PMID- 16803389
TI  - Strong effect of resonant impurities on Landau-level quantization.
AB  - We investigate experimentally the effect of a random distribution of nitrogen (N)
      impurities on the Landau-level spectrum of a GaAs quantum well. Our
      magnetotunneling study reveals complex and nonequally spaced Landau levels and a
      quenching of the Landau states at a well-defined bias and electron energy which
      is resonant with that of the N atoms. Analysis of the magnetic field dependence
      of the tunnel current into the Landau levels of the well also provides
      quantitative information about the nonresonant component of the N-related
      scattering potential.

PMID- 16803390
TI  - Strain-free polarization superlattice in silicon carbide: a theoretical
      investigation.
AB  - A strain-free superlattice of inversion domains along the hexagonal axis of SiC
      is investigated by theoretical calculations. The induced polarization causes a
      zigzag shape in the band edges, leading to spatial separation of photoexcited
      carriers and to an effective band gap narrowing tunable over a wide range by the
      geometry and on a smaller scale by the intensity of the excitation. Calculations
      on the SiC surface indicate that preparation of such a superlattice might be
      possible in atomic layer epitaxy with properly chosen sources and temperatures.

PMID- 16803391
TI  - Bichromatic microwave photoresistance of a two-dimensional electron system.
AB  - We explore experimentally bichromatic (frequencies omega(1) and omega(2))
      photoresistance of a two-dimensional electron system in the regimes of microwave
      induced resistance oscillations and zero-resistance states. We find bichromatic
      resistance to be well described by a superposition of omega(1) and omega(2) and
      components, provided that both monochromatic resistances are positive. This
      relation holds even when the oscillation amplitudes are small and one could
      expect additive contributions from monochromatic photoresistances. In contrast,
      whenever a zero-resistance state is formed by one of the frequencies, such
      superposition relation breaks down and the bichromatic resistance is strongly
      suppressed.

PMID- 16803392
TI  - Nodal structure of quasi-two-dimensional superconductors probed by a magnetic
      field.
AB  - We consider a quasi-two-dimensional superconductor with line nodes in the
      presence of an in-plane magnetic field, and compute the dependence of the
      specific heat C and the in-plane heat conductivity kappa on the angle between the
      field and the nodal direction in the vortex state. We use a variation of the
      microscopic Brandt-Pesch-Tewordt method that accounts for the scattering of
      quasiparticles off vortices, and analyze the signature of the nodes in C and
      kappa. At low to moderate fields the specific heat anisotropy changes sign with
      increasing temperature. Comparison with measurements of C and kappa in CeCoIn(5)
      resolves the contradiction between the two in favor of the d((x(2)-y(2)) gap.

PMID- 16803393
TI  - Quantum-classical correspondence in the wave functions of andreev billiards.
AB  - We present a classical and quantum mechanical study of an Andreev billiard with a
      chaotic normal dot. We demonstrate that the nonexact velocity reversal and the
      diffraction at the edges of the normal-superconductor contact render the
      classical dynamics of these systems mixed indicating the limitations of a widely
      used retracing approximation. We point out the close relation between the mixed
      classical phase space and the properties of the quantum states of Andreev
      billiards, including periodic orbit scarring and localization of the wave
      function onto other classical phase space objects such as intermittent regions
      and quantized tori.

PMID- 16803394
TI  - Probing the coulomb interaction of the unconventional superconductor by phonon
      spectroscopy.
AB  - The phonon dispersion curves of the superconductor PuCoGa(5) were studied by
      inelastic x-ray scattering at room temperature. The experimental data agree well
      with ab initio lattice dynamics calculations. An accurate description of the
      phonon spectrum is obtained only when a local Coulomb repulsion U approximately
      equal 3 eV among 5f electrons is taken into account.

PMID- 16803395
TI  - Stabilization of metastable expanded face-centered-tetragonal manganese.
AB  - The structural and magnetic properties of Mn prepared on single crystalline face
      centered-tetragonal (fct) Co(001) were investigated. Mn grows coherently up to at
      least 50 monolayers (ML) and adopts a metastable expanded fct(001) phase [c/a =
      1.055(5)]. This new fct-Mn phase was recently predicted theoretically by Hafner
      and Spisak. Studies of magnetic Mn/Co interface exchange interactions prove the
      room temperature antiferromagnetic state for thicknesses above 2.5 ML. The
      magnetic anisotropy of the thin Mn is high enough to induce a significant
      exchange anisotropy for Mn thicknesses as low as 6 ML. The potential of fct-Mn to
      become a novel model system for systematic studies on the exchange interactions
      at antiferromagnet/ferromagnet interfaces is discussed.

PMID- 16803396
TI  - Artificial square ice and related dipolar nanoarrays.
AB  - We study a frustrated dipolar array recently manufactured lithographically by
      Wang in order to realize the square ice model in an artificial structure. We
      discuss models for thermodynamics and dynamics of this system. We show that an
      ice regime can be stabilized by small changes in the array geometry; a different
      magnetic state, kagome ice, can similarly be constructed. At low temperatures,
      the square ice regime is terminated by a thermodynamic ordering transition, which
      can be chosen to be ferro- or antiferromagnetic. We show that the arrays do not
      fully equilibrate experimentally, and identify a likely dynamical bottleneck.

PMID- 16803397
TI  - Spin-resolved electronic structure of nanoscale cobalt islands on Cu(111).
AB  - Using spin-polarized scanning tunneling spectroscopy, we reveal how the standing
      wave patterns of confined surface state electrons on top of nanometer-scale
      ferromagnetic Co islands on Cu(111) are affected by the spin character of the
      responsible state, thus experimentally confirming a very recent theoretical
      result. Furthermore, at the rim of the islands a spin-polarized state is found
      giving rise to enhanced zero bias conductance. Its polarization is opposite to
      that of the islands. The experimental findings are in accordance with ab initio
      spin-density calculations.

PMID- 16803398
TI  - Transition temperature of a magnetic semiconductor with angular momentum j.
AB  - We employ dynamical mean-field theory to identify the materials properties that
      optimize T(c) for a generalized double-exchange model. We reach the surprising
      conclusion that T(c) achieves a maximum when the band angular momentum j equals
      3/2 and when the masses in the m(j) = +/- 1/2 and +/-3/2 and subbands are equal.
      However, we also find that T(c) is significantly reduced as the ratio of the
      masses decreases from one. Consequently, the search for dilute-magnetic
      semiconductor materials with high T(c) should proceed on two fronts. In
      semiconductors with p bands, such as the currently studied Mn-doped Ge and GaAs
      semiconductors, T(c) may be optimized by tuning the band masses through strain
      engineering or artificial nanostructures. On the other hand, semiconductors with
      s or d bands with nearly equal effective masses might prove to have higher T(c)'s
      than p-band materials with disparate effective masses.

PMID- 16803399
TI  - Strong universality and algebraic scaling in two-dimensional Ising spin glasses.
AB  - At zero temperature, two-dimensional Ising spin glasses are known to fall into
      several universality classes. Here we consider the scaling at low but nonzero
      temperatures and provide numerical evidence that eta approximately equal 0 and nu
      approximately equal 3.5 in all cases, suggesting a unique universality class.
      This algebraic (as opposed to exponential) scaling holds, in particular, for the
      +/- J model, with or without dilutions, and for the plaquette diluted model. Such
      a picture, associated with an exceptional behavior at T = 0, is consistent with a
      real space renormalization group approach. We also explain how the scaling of the
      specific heat is compatible with the hyperscaling prediction.

PMID- 16803400
TI  - Cooperative recombination of a quantized high-density electron-hole plasma in
      semiconductor quantum wells.
AB  - We investigate photoluminescence from a high-density electron-hole plasma in
      semiconductor quantum wells created via intense femtosecond excitation in a
      strong perpendicular magnetic field, a fully quantized and tunable system. At a
      critical magnetic field strength and excitation fluence, we observe a clear
      transition in the band-edge photoluminescence from omnidirectional output to a
      randomly directed but highly collimated beam. In addition, changes in the
      linewidth, carrier density, and magnetic field scaling of the photoluminescence
      spectral features correlate precisely with the onset of random directionality,
      indicative of cooperative recombination from a high-density population of free
      carriers in a semiconductor environment.

PMID- 16803401
TI  - Magnetic circular dichroism near the Fermi level.
AB  - We report the observation of enhanced magnetic circular dichroism (MCD) near the
      Fermi level using visible and ultraviolet lasers. More than 10% MCD asymmetry is
      achieved for a perpendicularly magnetized 12 ML (monolayer) Ni film on Cu(001).
      By changing the work function with the aid of cesium adsorption, the MCD
      asymmetry of is found to be enhanced only near the photoemission threshold and to
      drop down to 0.1% at the photon energy larger than the work function by 0.6 eV. A
      theoretical calculation also shows enhanced MCD near the photoemission threshold,
      qualitatively in agreement with the experimental results. Other ultrathin films
      of 6 ML Ni, 15 ML Co, and 3 and 15 ML Fe on Cu(001) are also investigated. It is
      found that the perpendicularly magnetized films show much larger MCD asymmetries
      than the in-plane magnetized films as in the Kerr effect.

PMID- 16803402
TI  - Probing the transition in bulk Ce under pressure: a direct investigation by
      resonant inelastic X-ray scattering.
AB  - We report on the most complete investigation to date of the -electron properties
      at the transition in elemental Ce by resonant inelastic x-ray scattering (RIXS).
      The Ce 2p3d-RIXS spectra were measured directly in the bulk material as a
      function of pressure through the transition. The spectra were simulated within
      the Anderson impurity model. The occupation number n(f) and f double occupancy
      were derived from the calculations in both gamma and alpha phases in the ground
      state. We find that the electronic structure changes result mainly from band
      formation of 4f electrons which concurs with reduced electron correlation and
      increased Kondo screening at high pressure.

PMID- 16803403
TI  - Controlling toroidal moment by means of an inhomogeneous static field: an ab
      initio study.
AB  - A first-principles-based approach is used to show (i) that stress-free
      ferroelectric nanodots under open-circuit-like electrical boundary conditions
      maintain a vortex structure for their local dipoles when subject to a transverse
      inhomogeneous static electric field, and, more importantly, (ii) that such a
      field leads to the solution of a fundamental and technological challenge: namely,
      the efficient control of the direction of the macroscopic toroidal moment. The
      effects responsible for such striking features are revealed and discussed.

PMID- 16803404
TI  - High resolution electromechanical imaging of ferroelectric materials in a liquid
      environment by piezoresponse force microscopy.
AB  - High-resolution imaging of ferroelectric materials using piezoresponse force
      microscopy (PFM) is demonstrated in an aqueous environment. The elimination of
      both long-range electrostatic forces and capillary interactions results in a
      localization of the ac field to the tip-surface junction and allows the tip
      surface contact area to be controlled. This approach results in spatial
      resolutions approaching the limit of the intrinsic domain-wall width. Imaging at
      frequencies corresponding to high-order cantilever resonances minimizes the
      viscous damping and added mass effects on cantilever dynamics and allows
      sensitivities comparable to ambient conditions. PFM in liquids will provide novel
      opportunities for high-resolution studies of ferroelectric materials, imaging of
      soft polymer materials, and imaging of biological systems in physiological
      environments on, ultimately, the molecular level.

PMID- 16803405
TI  - Observation of the first-order transition in ultrafiltration of flexible linear
      polymer chains.
AB  - Using a special double-layer membrane to avoid interaction among flow fields
      generated by different pores, we have, for the first time, observed the predicted
      discontinuous first-order transition in ultrafiltration of flexible linear
      polymer chains. Namely, the chain could pass through a pore much smaller than its
      unperturbed radius only when the flow rate is higher than a certain value. When
      only one chain and one pore are considered in theory, such a threshold is
      surprisingly independent of both the chain length and the pore size. Our results
      reveal that for a membrane with many pores and at a microscopic flow rate ()
      lower than the threshold, the inevitable blocking of some pores by longer
      nonstretched coiled chains increases in those unblocked pores because the
      macroscopic flow rate () is a constant. Long chains have two populations, coiled
      and stretched, in a real ultrafiltration experiment when is lower than the
      threshold.

PMID- 16803406
TI  - Nonlinear photoresponse of disordered elastomers.
AB  - We model the polarization-dependent photocontractions of polydomain nematic
      elastomers. Contraction initially arises by light-induced director rotation. At
      higher light intensity, strain recovers because the local order parameter
      diminishes. Thus we predict photostrains to be nonmonotonic with light intensity
      and predict the induction of a negative global order parameter for the system of
      polydomains. Nonmonotonic strains would give curvature reversal in thick samples.
      Our model also predicts an elongational strain response to nonpolarized light.

PMID- 16803407
TI  - Reproducibility of dynamical heterogeneities and metabasin dynamics in glass
      forming liquids: the influence of structure on dynamics.
AB  - The discovery that the propensity for particle motion in a supercooled liquid is
      completely determined by the initial structure pointed to the existence of a
      causal link between structure and dynamics in glassy systems. Here we demonstrate
      that this underlying influence of structure is only local in time, fading out
      beyond the metabasin lifetime much before the relaxation time. Thus, our results
      reveal the irreproducibility of metabasin dynamics and support the scenario of a
      random walk on metabasins for the long time diffusion.

PMID- 16803408
TI  - Surface plasmon radiation forces.
AB  - We report the first experimental observation of momentum transfer from a surface
      plasmon to a single dielectric sphere. Using a photonic force microscope, we
      measure the plasmon radiation forces on different polystyrene beads as a function
      of their distance from the metal surface. We show that the force magnitude at
      resonance is strongly enhanced compared to a nonresonant illumination.
      Measurements performed as a function of the probe particle size indicate that
      optical manipulation by plasmon fields has a strong potential for optical
      sorting.

PMID- 16803409
TI  - Protein folding kinetics and thermodynamics from atomistic simulations.
AB  - Determining protein folding kinetics and thermodynamics from all-atom molecular
      dynamics (MD) simulations without using experimental data represents a formidable
      scientific challenge because simulations can easily get trapped in local minima
      on rough free energy landscapes. This necessitates the computation of multiple
      simulation trajectories, which can be independent from each other or coupled in
      some manner, as, for example, in the replica exchange MD method. Here we present
      results obtained with a new analysis tool that allows the deduction of faithful
      kinetics data from a heterogeneous ensemble of simulation trajectories. The
      method is demonstrated on the decapeptide Chignolin for which we predict folding
      and unfolding time constants of 1.0 +/- 0.3 and 2.6 +/- 0.4 micros, respectively.
      We also derive the energetics of folding, and calculate a realistic melting curve
      for Chignolin.

PMID- 16803410
TI  - Multiprotein DNA looping.
AB  - DNA looping plays a fundamental role in a wide variety of biological processes,
      providing the backbone for long range interactions on DNA. Here we develop the
      first model for DNA looping by an arbitrarily large number of proteins and solve
      it analytically in the case of identical binding. We uncover a switchlike
      transition between looped and unlooped phases and identify the key parameters
      that control this transition. Our results establish the basis for the
      quantitative understanding of fundamental cellular processes like DNA
      recombination, gene silencing, and telomere maintenance.

PMID- 16803411
TI  - Confinement-driven translocation of a flexible polymer.
AB  - We consider the escape of a flexible, self-avoiding polymer chain out of a
      confined geometry. By means of simulations, we demonstrate that the translocation
      time can be described by a simple scaling law that exhibits a nonlinear
      dependence on the degree of polymerization and that is sensitive to the nature of
      the confining geometry. These results contradict earlier predictions but are in
      agreement with recently confirmed geometry-dependent expressions for the free
      energy of confinement.

PMID- 16803412
TI  - Spatial persistence of angular correlations in amyloid fibrils.
AB  - Using atomic force microscopy height maps, we resolve and quantify torsional
      fluctuations in one-dimensional amyloid fibril aggregates self-assembled from
      three different representative polypeptide systems. Furthermore, we show that
      angular correlation in these nanoscale structures is maintained over several
      microns, corresponding to many thousands of molecules along the fibril axis. We
      model disorder in the fibril in respect of both thermal fluctuations and
      structural defects, and determine quantitative values for the defect density, as
      well as the energy scales involved in the fundamental interactions stabilizing
      these generic structures.

PMID- 16803413
TI  - Molecular observation of constraint release in polymer melts.
AB  - The dynamics of binary polymer blends of few labeled long chains in successively
      shorter matrix chains has been investigated by neutron spin echo (NSE)
      spectroscopy. For the first time the effect of constraint release on the chain
      relaxation has been directly observed on a microscopic scale. Decreasing the
      matrix chain length reduces the topological confinement until unconfined Rouse
      motion is observed, when the matrix chains are too short to confine the long
      chain in a tube. Whereas an analytical description of the effect is not yet
      available, a new simulation based on the slip-link model shows perfect agreement
      with the NSE data over the full range of matrix molecular weights.

PMID- 16803414
TI  - Direct observation of anharmonic coupling in the time domain with femtosecond
      stimulated Raman scattering.
AB  - Off-resonant impulsive Raman excitation is used to initiate nonstationary nuclear
      motion in low-frequency vibrational modes of deuterio-chloroform. Femtosecond
      time-resolved stimulated Raman probing of the high-frequency C-D stretch reveals
      additional vibrational sidebands that arise as a result of anharmonic coupling
      between the impulsively excited low-frequency and the probed high-frequency
      vibrations. These experiments illustrate the detailed molecular information on
      anharmonic and reactive surfaces available from multidimensional femtosecond
      stimulated Raman techniques.

PMID- 16803415
TI  - Complex network from pseudoperiodic time series: topology versus dynamics.
AB  - We construct complex networks from pseudoperiodic time series, with each cycle
      represented by a single node in the network. We investigate the statistical
      properties of these networks for various time series and find that time series
      with different dynamics exhibit distinct topological structures. Specifically,
      noisy periodic signals correspond to random networks, and chaotic time series
      generate networks that exhibit small world and scale free features. We show that
      this distinction in topological structure results from the hierarchy of unstable
      periodic orbits embedded in the chaotic attractor. Standard measures of structure
      in complex networks can therefore be applied to distinguish different dynamic
      regimes in time series. Application to human electrocardiograms shows that such
      statistical properties are able to differentiate between the sinus rhythm
      cardiograms of healthy volunteers and those of coronary care patients.

PMID- 16803416
TI  - Comment on "Can one predict DNA transcription start sites by studying bubbles?".

PMID- 16803418
TI  - Statin-associated pleiotropy: possible beneficial effects beyond cholesterol
      reduction.
AB  - Because elevated serum cholesterol levels are strongly associated with coronary
      heart disease, cholesterol reduction by 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (or statins) has been assumed to be the predominant, if not
      the only, mechanism underlying the beneficial effects of these drugs in
      cardiovascular diseases. Subgroup analyses of large clinical trials, however,
      have suggested that the beneficial effects of statins may extend to mechanisms
      beyond cholesterol reduction. Indeed, recent experimental and clinical evidence
      indicates that some of the cholesterol-independent or "pleiotropic" effects of
      statins may be mediated through improving or restoring endothelial function,
      enhancing the stability of atherosclerotic plaques, and decreasing oxidative
      stress and vascular inflammation.

PMID- 16803420
TI  - Randomized, double-blind, crossover comparison of amlodipine and valsartan in
      african-americans with hypertension using 24-hour ambulatory blood pressure
      monitoring.
AB  - STUDY OBJECTIVE: To compare the efficacy of amlodipine and valsartan in African
      American patients with hypertension using ambulatory blood pressure monitoring
      (ABPM). DESIGN: Prospective, randomized, double-blind, crossover comparison
      study. SETTING: University-affiliated cardiac center clinic. PATIENTS: Twenty
      African-Americans (12 men, 8 women), with a history of uncomplicated hypertension
      (blood pressure > 140/90 mm Hg). INTERVENTION: Patients were randomized to
      receive amlodipine 5 or 10 mg/day or valsartan 80 or 160 mg/day for 8-10 weeks,
      depending on response. Dosages were titrated to achieve a blood pressure of
      140/90 mm Hg or below. For patients whose blood pressures were not controlled,
      hydrochlorothiazide 12.5 mg/day was added to their regimens. Patients then
      underwent 24-hour ABPM. After an intervening washout period during which baseline
      blood pressure was reestablished, patients received the other treatment.
      MEASUREMENTS AND MAIN RESULTS: Mean +/- SD baseline blood pressure before the two
      ABPM periods were 155 +/- 12/100 +/- 8 mm Hg and 156 +/- 11/101 +/- 9 mm Hg,
      respectively. Fifteen (75%) patients achieved goal blood pressure with amlodipine
      and 14 (70%) with valsartan (p=0.62). Final daily dosages were as follows:
      amlodipine 5 mg in nine patients, 10 mg in five patients, and 10 mg plus
      hydrochlorothiazide in six patients; valsartan 80 mg in nine patients, 160 mg in
      four patients, and 160 mg plus hydrochlorothiazide in seven patients. Ambulatory
      blood pressure monitoring was not completed in three patients due to adverse
      effects: headache and dizziness (one patient each, amlodipine and valsartan) and
      hyperkalemia (one patient, valsartan). Four patients (20%) in each treatment
      group had drug-related adverse effects. Results of ABPM including averages for 24
      hour, daytime, nighttime, first 4 hours, and last 8 hours, and trough:peak ratios
      were not significantly different between the amlodipine- and valsartan-based
      treatments. CONCLUSION: Based on both clinic blood pressure measurements and ABPM
      data, amlodipine and valsartan produced similar reductions in blood pressure in
      African-American patients with uncomplicated hypertension.

PMID- 16803421
TI  - Pharmacologic management of constipation in the critically ill patient.
AB  - STUDY OBJECTIVE: To compare the effectiveness of common laxatives in producing a
      bowel movement in patients admitted to a medical intensive care unit (MICU).
      DESIGN: Retrospective medical record review. SETTING: MICU of an academic medical
      center. PATIENTS: Ninety-five patients admitted to the MICU from July 1-October
      31, 2004. MEASUREMENTS AND MAIN RESULTS: Fifty patients satisfied the inclusion
      criteria. Patient-specific data such as age, weight, sex, length of MICU stay,
      Acute Physiology and Chronic Health Evaluation (APACHE) II score, dietary intake,
      opioid intake, laxative intake, and bowel movements were recorded during the
      first 96 hours of admission. Logistic regression analysis was used to compare
      patients who did and did not have a bowel movement. Of the 50 patients, 25 did
      not have a bowel movement during the first 96 hours of MICU admission. Patients
      given a stimulant laxative (senna, bisacodyl) and/or an osmotic laxative
      (lactulose, milk of magnesia) were more likely to have a bowel movement (odds
      ratio [OR] 26.6, 95% confidence interval [CI] 3.2-221, p=0.002). Opioid intake,
      expressed as logarithmic morphine equivalents, was negatively associated with
      occurrence of a bowel movement (OR 0.76, 95% CI 0.59-0.97, p=0.027). Disease
      severity, as determined by APACHE II score, was also negatively associated with a
      bowel movement (OR 0.84, 95% CI 0.7-0.99, p=0.04). CONCLUSION: Critically ill
      patients have a high frequency of constipation, and opioid therapy is a
      significant risk factor. Routine administration of stimulant or osmotic laxatives
      should be considered for this patient population.

PMID- 16803422
TI  - Disposition of imatinib and its metabolite CGP74588 in a patient with chronic
      myelogenous leukemia and short-bowel syndrome.
AB  - Imatinib mesylate, licensed to treat chronic myelogenous leukemia and
      gastrointestinal stromal tumors, is metabolized by means of cytochrome P450 3A
      and excreted primarily in the bile. Although the bioavailability of imatinib
      mesylate is more than 97%, the exact gastrointestinal site of its absorption is
      unknown. Liquid chromatography-mass spectrometry was used to quantitate imatinib
      and its metabolite CGP74588 in the plasma and jejunostomy output of a patient
      with newly diagnosed chronic myelogenous leukemia. She had previously lost most
      of her small bowel and all of her colon as a result of mesenteric artery
      thrombosis and radiation-induced colitis and/or proctitis. Imatinib
      pharmacokinetics in plasma indicated that approximately 20% of the patient's 400
      mg dose was absorbed. The jejunostomy output contained 338 mg of imatinib, which
      was consistent with 320 mg of a nonabsorbed dose plus approximately 23% of the
      absorbed dose being excreted unchanged in the bile. These data indicate the
      importance of considering gastrointestinal anatomic abnormalities or disease
      states when oral imatinib is dosed.

PMID- 16803424
TI  - Cardiovascular risks of cyclooxygenase inhibition.
AB  - Millions of patients use nonsteroidal antiinflammatory drugs (NSAIDs) for relief
      of arthritic pain. Although NSAIDs reduce pain, their use has been linked to
      gastroduodenal complications. Selective inhibition of the cyclooxygenase (COX)-2
      enzyme appeared to offer patients similar pain relief with an improved adverse
      effect profile. However, accumulating experiences have raised concerns regarding
      the cardiovascular toxicities of the selective COX-2 inhibitors. Although
      selective COX inhibitors provide more gastrointestinal protection than NSAIDs,
      the unbalanced inhibition of prostaglandins may promote cardiovascular
      complications. Variability in study designs and inconsistency in results have
      made the evaluation of NSAID and COX-2 inhibitor safety very difficult, creating
      confusion among health care practitioners. We examine the pharmacologic and
      clinical evidence that defines the cardiovascular risk associated with COX
      inhibition.

PMID- 16803423
TI  - Dalbavancin: a novel lipoglycopeptide antibacterial.
AB  - Dalbavancin is a new lipoglycopeptide antibacterial possessing in vitro activity
      against a variety of gram-positive pathogens. Against methicillin-susceptible and
      methicillin-resistant Staphylococcus aureus, it has demonstrated favorable
      minimum inhibitory concentration ranges compared with those of currently
      available agents. Dalbavancin is highly protein bound (> 90%), which may
      contribute to its prolonged half-life of 149-300 hours. Because of this long half
      life, once-weekly dosing strategies have been used in clinical trials. Efficacy
      and tolerability have been demonstrated in a wide variety of animal infection
      models. Clinical success and safety have been shown in phase II and III trials
      for skin and soft-tissue infections and a phase II trial for catheter-related
      bloodstream infections. In these trials with vancomycin, linezolid, and various
      beta-lactams as comparators, comparable results have been reported. The results
      of further phase III trials are anxiously awaited and will more clearly define
      the clinical role of this novel agent.

PMID- 16803425
TI  - Key articles, guidelines, and consensus papers relative to the treatment of
      dyslipidemias--2005.
AB  - Hypercholesterolemia is a major risk factor for development of coronary heart
      disease. Proper diagnosis and adequate treatment are vital to reducing morbidity
      and mortality associated with elevated serum lipid levels. The amount of
      literature in this area is overwhelming. To aid practitioners and educators in
      organizing this large body of information, we compiled key articles, guidelines,
      and consensus papers relative to the treatment of dyslipidemias. Research
      articles were chosen based on the significance of findings, relevance to
      practice, quality of research, and timeliness; recent articles were given
      priority over earlier ones unless they demonstrated groundbreaking findings.

PMID- 16803427
TI  - The state of science and research in clinical pharmacy.

PMID- 16803426
TI  - Thalidomide-induced severe hepatotoxicity.
AB  - Thalidomide is a relatively safe and efficacious form of therapy in the treatment
      of advanced, refractory multiple myeloma. Hepatotoxicity is listed as an
      extremely rare adverse effect associated with its use. We describe a 76-year-old
      woman with multiple myeloma who was treated with dexamethasone and thalidomide.
      By week 6 of therapy, she had developed acute increases in her aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels to more than 50
      times the upper limit of normal. Her liver function test results had been within
      the normal ranges before and immediately after the start of therapy, and the
      patient had no known history of underlying liver disease. A liver biopsy specimen
      demonstrated evidence of acute injury with chronic changes of underlying
      steatosis and bridging fibrosis due to previously undiagnosed nonalcoholic
      steatohepatitis. Immediately after discontinuing thalidomide, her liver function
      test results began trending downward. Seven days later, her AST and ALT levels
      had improved to 86 and 165 U/L, respectively. This case and a limited number of
      other reports demonstrate severe hepatotoxicity as a rare but potentially serious
      adverse effect of thalidomide therapy. With the expanding use of thalidomide as a
      therapeutic agent, clinicians must recognize severe hepatotoxicity as a potential
      complication. Whether patients with preexisting liver disease are at increased
      risk when receiving thalidomide remains to be seen.

PMID- 16803428
TI  - Estimation of glomerular filtration rate in the elderly: Cockcroft-Gault formula
      versus modification of diet in renal disease formula.

PMID- 16803429
TI  - Orchestrating the growth of pharmacy as a clinical profession--a comment.

PMID- 16803430
TI  - Implications of thiazolidinedione use and cardiovascular risk: is it all about
      the sugar?

PMID- 16803431
TI  - Neural crest stem and progenitor cells.
AB  - Neural crest cells are a multipotent, migratory cell population that generates an
      astonishingly diverse array of cell types during vertebrate development. These
      include bones; tendons; neurons; glia; melanocytes; and connective, endocrine,
      and adipose tissue. With a limited capacity for self-renewal and a wide range of
      differentiation fates, neural crest cells bear many of the hallmarks of stem
      cells and persist throughout embryonic and adult development. But are all neural
      crest cells true stem cells, or do the majority of neural crest cells more
      closely resemble progenitor cells? In this review we discuss recent advances in
      characterizing the properties of neural crest cells, together with their
      potential for tissue-specific repair.

PMID- 16803432
TI  - Emergency department frequent flyers: unnecessary load or a lifeline?

PMID- 16803433
TI  - Killing the messenger: should scientific journals be responsible for policing
      scientific fraud?

PMID- 16803434
TI  - The Greater Metropolitan Clinical Taskforce: an Australian model for clinician
      governance.

PMID- 16803435
TI  - Hospital in the home: a concept under question.

PMID- 16803436
TI  - Should clinical software be regulated?

PMID- 16803437
TI  - The effect of multidisciplinary case management on selected outcomes for frequent
      attenders at an emergency department.
AB  - OBJECTIVE: To evaluate the effects of multidisciplinary case management (CM) on
      emergency department (ED) utilisation and psychosocial variables for frequent
      attenders at the ED. DESIGN: Retrospective cohort analysis, with the study
      population as historical controls and data analysed 12 months before and after CM
      intervention in the period 1 January 2000 - 31 December 2004. Subgroup analyses
      were performed according to primary problem categories: general medical, drug and
      alcohol, and psychosocial. SETTING: Inner urban tertiary hospital ED.
      PARTICIPANTS: Frequent ED attenders who received CM. MAIN OUTCOME MEASURES: ED
      attendances: length of stay, triage category, ambulance transport, disposition,
      attendances at the only two EDs nearby. Psychosocial factors: housing status,
      drug and alcohol use, and primary and community care engagement. RESULTS: 60 CM
      patients attended the ED on 1387 occasions. Total attendances increased after CM
      for the whole group (610 v 777, P = 0.055). Mean average length of stay (minutes)
      of the total study population and each subgroup was unaffected by CM (297 v 300,
      P = 0.8). Admissions for ED overnight observation increased as a result of CM (P
      = 0.025). CM increased scores for housing stability (P = 0.007), primary care
      linkage (P = 0.003), and community care engagement (P < 0.001) for the whole
      group and variously within subgroups. Drug and alcohol use was unaffected by CM.
      CONCLUSION: ED-initiated, multidisciplinary CM appears to increase ED utilisation
      and have a positive effect on some psychosocial factors for frequent attenders. A
      trend towards increased ED attendance and utilisation with CM may have
      implications for policies that seek to divert frequent attenders away from
      hospitals.

PMID- 16803438
TI  - Epilepsy in Indigenous and non-Indigenous people in Far North Queensland.
AB  - OBJECTIVE: To compare patterns of epilepsy in Indigenous and non-Indigenous
      people presenting to hospital. STUDY DESIGN: Retrospective cross-sectional survey
      of individuals admitted to hospital with a diagnosis of epilepsy (1 January 2001 
      31 December 2004); presenting to the emergency department with a seizure (2004);
      or presenting to the epilepsy clinic (1 September 2002-31 March 2005). SETTING:
      Cairns Base Hospital, the major referral centre for Far North Queensland,
      including Cape York and the Torres Strait, with a population of 230 000 (13%
      Indigenous). MAIN OUTCOME MEASURES: Proportion of Indigenous patients presenting
      for epilepsy; proportion of Indigenous and non-Indigenous groups affected by each
      of the main epilepsy syndromes. RESULTS: Of 359 patients attending the epilepsy
      clinic and 918 patients having electroencephalography (EEG), 11% and 13% were
      Indigenous, respectively (in proportion with the catchment population). However,
      30% (146/486) of patients presenting to the emergency department with seizure,
      31% (130/418) of inpatient admissions with epilepsy, and 44% (28/63) of patients
      admitted with status epilepticus were Indigenous. Indigenous patients were more
      likely to have an abnormal EEG result (P = 0.025), while non-Indigenous patients
      presenting to the clinic were more likely to be classified as non-epileptic (31%
      v 18%). In those with abnormal EEG, the frequency distribution of abnormalities
      was similar, and, in those with epilepsy, syndrome classification also showed
      similar frequencies. There was no significant difference in occurrence of
      epileptogenic abnormalities detected by imaging (13% non-Indigenous v 18%
      Indigenous) or in alcohol consumption (38% v 37%). CONCLUSIONS: Indigenous
      Australians have similar epilepsy syndromes to the non-Indigenous population, but
      they present with more serious disease. This discrepancy may relate to
      inequitable health care utilisation due to cultural issues or geographic
      isolation.

PMID- 16803439
TI  - Postpartum anti-D: can we safely reduce the dose?
AB  - OBJECTIVE: To assess the potential for dose-reduction of prophylactic anti-D
      postpartum. DESIGN: Retrospective audit of fetomaternal haemorrhage (FMH)
      quantitation by flow cytometry. PARTICIPANTS AND SETTING: 5148 consecutive Rhesus
      D-negative women aged 15-45 years who had FMH estimation by flow cytometry at a
      central laboratory in Western Australia in the 65 months between 1 August 1999
      and 31 January 2005. MAIN OUTCOME MEASURES: Quantitation of FMH volume for
      adequate prophylactic anti-D administration in a timely fashion. RESULTS: 90.4%
      (4651/5148) of the women had an FMH volume of 1.0 mL or less of Rh D-positive red
      cells, and 98.5% (5072/5148) had a volume of less than 2.5 mL. Only 0.4% of cases
      had an FMH volume of 6.0 mL or greater (range, 6.0-92.4 mL). CONCLUSIONS: This
      large retrospective audit shows that a currently available dose of 250 IU (50 mg)
      of anti-D would have been sufficient for 98.5% of the 5148 Rh D-negative women.
      On the basis of this evidence, a reduction in the recommended routine postpartum
      dose of anti-D from 625 IU to 250 IU when flow cytometric quantitation for FMH is
      available should be considered. Adopting such a strategy would ensure the ongoing
      provision of a valuable human blood product currently in limited supply.

PMID- 16803440
TI  - Ultrasonography in diagnosing colorectal cancers in patients presenting with
      abdominal distension.
AB  - OBJECTIVE: To determine the usefulness of abdominal ultrasonography for
      diagnosing colorectal cancer in patients presenting with abdominal distension.
      DESIGN, SETTING AND PARTICIPANTS: A prospective case series of consecutive adult
      patients with abdominal distension admitted to the National Taiwan University
      Hospital between January 2001 and July 2004. All participants were examined by
      abdominal ultrasonography. Those with suspected colorectal tumours on
      ultrasonography had follow-up colonoscopy, while all other patients had computed
      tomography scans. MAIN OUTCOME MEASURES: Accuracy of abdominal ultrasonography
      for diagnosing colorectal cancer in patients with abdominal distension; incidence
      of colorectal cancer. RESULTS: Of 511 patients eligible for inclusion in our
      study, 97 (19.0%) were confirmed to have colorectal cancer. For diagnosis of
      colorectal cancer, ultrasonography had a sensitivity of 92.8% (95% CI, 85.2%
      96.8%); a specificity of 98.8% (95% CI, 97.0%-99.6%); a positive predictive value
      of 94.7% (95% CI, 87.6%-98.0%); a negative predictive value of 98.3% (95% CI
      96.4%-99.3%); and an accuracy of 97.7%. CONCLUSION: Ultrasonography is a
      sensitive tool for diagnosing colorectal cancer in patients presenting with
      abdominal distension.

PMID- 16803441
TI  - Iodine status in pregnant women and their newborns: are our babies at risk of
      iodine deficiency?
AB  - OBJECTIVES: To determine whether pregnant women and their newborns show evidence
      of iodine deficiency, and to examine the correlation between maternal urine
      iodine concentration (UIC) and newborn thyroid-stimulating hormone (TSH) level.
      DESIGN: A cross-sectional study. SETTING: Hospital antenatal care services (March
      May 2004) and private obstetrician clinics (June 2004) in the Central Coast area
      of New South Wales. PARTICIPANTS: 815 pregnant women (> or = 28 weeks' gestation)
      and 824 newborns. MAIN OUTCOME MEASURES: World Health Organization/International
      Council for the Control of Iodine Deficiency Disorders criteria for assessing
      severity of iodine deficiency (recommended levels: < 20% of urine samples in a
      population with UIC < 50 microg/L; and < 3% of newborns with whole-blood TSH
      level > 5 mIU/L). RESULTS: The median UIC for pregnant women was 85 microg/L,
      indicating mild iodine deficiency. Almost 17% of pregnant women had a UIC < 50
      microg/L, and 18 newborns (2.2%) had TSH values > 5 mIU/L. There was no
      statistically significant linear correlation between neonatal whole-blood TSH
      level and maternal UIC (r = - 0.03; P = 0.4). Mothers with a UIC < 50 microg/L
      were 2.6 times (relative risk = 2.65; 95% CI, 1.49-4.73; P = 0.01) more likely to
      have a baby with a TSH level > 5 mIU/L. CONCLUSION: The pregnant women surveyed
      were mildly iodine deficient. TSH values for their newborns were mostly within
      acceptable limits. Ongoing surveillance of the iodine status of NSW communities
      to establish trends over time is recommended.

PMID- 16803442
TI  - Predictors of publication: characteristics of submitted manuscripts associated
      with acceptance at major biomedical journals.
AB  - OBJECTIVE: To identify characteristics of submitted manuscripts that are
      associated with acceptance for publication by major biomedical journals. DESIGN,
      SETTING AND PARTICIPANTS: A prospective cohort study of manuscripts reporting
      original research submitted to three major biomedical journals (BMJ and the
      Lancet [UK] and Annals of Internal Medicine [USA]) between January and April 2003
      and between November 2003 and February 2004. Case reports on single patients were
      excluded. MAIN OUTCOME MEASURES: Publication outcome, methodological quality,
      predictors of publication. RESULTS: Of 1107 manuscripts enrolled in the study, 68
      (6%) were accepted, 777 (70%) were rejected outright, and 262 (24%) were rejected
      after peer review. Higher methodological quality scores were associated with an
      increased chance of acceptance (odds ratio [OR], 1.39 per 0.1 point increase in
      quality score; 95% CI, 1.16-1.67; P < 0.001), after controlling for study design
      and journal. In a multivariate logistic regression model, manuscripts were more
      likely to be published if they reported a randomised controlled trial (RCT) (OR,
      2.40; 95% CI, 1.21-4.80); used descriptive or qualitative analytical methods (OR,
      2.85; 95% CI, 1.51-5.37); disclosed any funding source (OR, 1.90; 95% CI, 1.01
      3.60); or had a corresponding author living in the same country as that of the
      publishing journal (OR, 1.99; 95% CI, 1.14-3.46). There was a non-significant
      trend towards manuscripts with larger sample size (>/= 73) being published (OR,
      2.01; 95% CI, 0.94-4.32). After adjustment for other study characteristics,
      having statistically significant results did not improve the chance of a study
      being published (OR, 0.83; 95% CI, 0.34-1.96). CONCLUSIONS: Submitted manuscripts
      are more likely to be published if they have high methodological quality, RCT
      study design, descriptive or qualitative analytical methods and disclosure of any
      funding source, and if the corresponding author lives in the same country as that
      of the publishing journal. Larger sample size may also increase the chance of
      acceptance for publication.

PMID- 16803443
TI  - Challenges in the diagnosis of Marfan syndrome.
AB  - Marfan syndrome (MFS) is a multisystem disorder of connective tissue that is
      inherited in an autosomal dominant fashion, and results from mutations in the
      FBN1 gene on chromosome 15. Diagnosis is challenging as it requires definition of
      diverse clinical features and input from a variety of specialists. Genetic
      testing of FBN1 is time consuming, expensive and complex, and may not solve the
      diagnostic dilemma. Failure to make a diagnosis or making an inappropriate
      diagnosis of MFS has social, lifestyle and medical consequences for the
      individual as well as the family.

PMID- 16803444
TI  - What can we learn from the Hwang and Sudbo affairs?
AB  - The recent publication, in prestigious scientific journals, of two major studies
      that were subsequently shown to contain fabricated data may compel reviewers and
      editors to adopt a more rigorous policy in accepting articles for publication.
      The current manner of peer reviewing research articles provides no assurance that
      the proffered work is not the result of fraud. The present guidelines for
      contributors in large team investigations may need to be updated to avoid giving
      credit to co-authors who may have made little, if any, contribution to the work.

PMID- 16803445
TI  - The repeating history of objections to the fortification of bread and alcohol:
      from iron filings to folic acid.
AB  - The fortification of staple foods has eliminated many deficiency diseases.
      Despite this, "tampering" with people's food always provokes opposition, much of
      it from health professionals. Opposition is often based on self-interest, tunnel
      vision and theory rather than research. A historical perspective of the patterns
      of objections to fortification and its outcomes may help resolve the anxieties
      and opposing ethical positions of advocates and opponents of fortification.

PMID- 16803446
TI  - Slowly progressive cranial nerve palsies.

PMID- 16803447
TI  - Lower-back pain, intervertebral-disc calcification and scleral pigmentation.

PMID- 16803448
TI  - "Positive" family planning: another personal viewpoint.

PMID- 16803449
TI  - A call for help. Australia needs a standard emergency phone number in all
      hospitals.

PMID- 16803450
TI  - Substance misuse in patients with acute mental illness.

PMID- 16803451
TI  - Health services research in Hungary.

PMID- 16803452
TI  - Adverse drug events: counting is not enough, action is needed.

PMID- 16803453
TI  - High-cost users of hospital beds in Western Australia.

PMID- 16803454
TI  - The research quality framework.

PMID- 16803455
TI  - Statins inhibit the dimerization of beta-secretase via both isoprenoid- and
      cholesterol-mediated mechanisms.
AB  - We have previously reported that protein lipidation in the form of palmitoylation
      and farnesylation is critical for the production of Abeta (amyloid beta-peptide),
      the dimerization of beta-secretase and its trafficking into cholesterol-rich
      microdomains. As statins influence these lipid modifications in addition to their
      effects on cholesterol biosynthesis, we have investigated the effects of
      lovastatin and SIMVA (simvastatin) at a range of concentrations chosen to
      distinguish different cellular effects on Abeta production and beta-secretase
      structure and its localization in bHEK cells [HEK-293 cells (human embryonic
      kidney cells) transfected with the Asp-2 gene plus a polyhistidine coding tag]
      cells. We have compared the changes brought about by statins with those brought
      about by the palmitoylation inhibitor cerulenin and the farnesyltransferase
      inhibitor CVFM (Cys-Val-Phe-Met). The statin-mediated reduction in Abeta
      production correlated with an inhibition of beta-secretase dimerization into its
      more active form at all concentrations of statin investigated. These effects were
      reversed by the administration of mevalonate, showing that these effects were
      mediated via 3-hydroxy-3-methylglutaryl-CoA-dependent pathways. At low (1 microM)
      statin concentrations, reduction in Abeta production and inhibition of beta
      secretase dimerization were mediated by inhibition of isoprenoid synthesis. At
      high (>10 microM) concentrations of statins, inhibition of beta-secretase
      palmitoylation occurred, which we demonstrated to be regulated by intracellular
      cholesterol levels. There was also a concomitant concentration-dependent change
      in beta-secretase subcellular trafficking. Significantly, Abeta release from
      cells was markedly higher at 50 microM SIMVA than at 1 microM, whereas these
      concentrations resulted in similar reductions in total Abeta production,
      suggesting that low-dose statins may be more beneficial than high doses for the
      therapeutic treatment of Alzheimer's disease.

PMID- 16803456
TI  - Inducible nitric oxide synthase activity does not contribute to the maintenance
      of peripheral vascular tone in patients with heart failure.
AB  - Enhanced iNOS (inducible nitric oxide synthase) activity may contribute to
      vascular dysfunction in patients with heart failure. In the present study, we
      aimed to determine whether iNOS activity contributes to the maintenance of
      vascular tone in patients with symptomatic heart failure with the use of the
      highly selective iNOS inhibitor 1400W {N-[3-(aminomethyl)benzyl] acetamidine}.
      Bilateral forearm blood flow was measured using venous occlusion plethysmography
      in 12 patients with New York Heart Association class II-IV heart failure and
      eight matched healthy control subjects during intra-brachial infusion of 1400W
      (0.1-1 micromol/min), L-NMMA (N(G)-monomethyl-L-arginine; a non-selective NOS
      inhibitor; 2-8 micromol/min) and noradrenaline (control vasoconstrictor; 60-480
      pmol/min). In both patients and controls, intra-brachial infusion of L-NMMA and
      noradrenaline caused a dose-dependent reduction in infused forearm blood flow
      (P<0.05 for both): peak reduction of 32+/-6% and 37+/-4% during L-NMMA and 52+/
      6% and 49+/-5% during noradrenaline respectively (P values were not significant
      when patients were compared with controls). In contrast, 1400W had no effect on
      blood flow at 1 micromol/min [-3+/-4% in patients (95% confidence intervals, -11
      to 5%) and 3+/-8% in controls; P value was not significant]. In conclusion, we
      have demonstrated that intrabrachial selective iNOS inhibition does not influence
      forearm blood flow in patients with heart failure. We conclude that iNOS activity
      does not contribute to peripheral vascular tone in patients with symptomatic
      heart failure.

PMID- 16803458
TI  - Structural basis for non-competitive product inhibition in human thymidine
      phosphorylase: implications for drug design.
AB  - HTP (human thymidine phosphorylase), also known as PD-ECGF (platelet-derived
      endothelial cell growth factor) or gliostatin, has an important role in
      nucleoside metabolism. HTP is implicated in angiogenesis and apoptosis and
      therefore is a prime target for drug design, including antitumour therapies. An
      HTP structure in a closed conformation complexed with an inhibitor has previously
      been solved. Earlier kinetic studies revealed an ordered release of thymine
      followed by ribose phosphate and product inhibition by both ligands. We have
      determined the structure of HTP from crystals grown in the presence of thymidine,
      which, surprisingly, resulted in bound thymine with HTP in a closed dead-end
      complex. Thus thymine appears to be able to reassociate with HTP after its
      initial ordered release before ribose phosphate and induces the closed
      conformation, hence explaining the mechanism of non-competitive product
      inhibition. In the active site in one of the four HTP molecules within the
      crystal asymmetric unit, additional electron density is present. This density has
      not been previously seen in any pyrimidine nucleoside phosphorylase and it
      defines a subsite that may be exploitable in drug design. Finally, because our
      crystals did not require proteolysed HTP to grow, the structure reveals a loop
      (residues 406-415), disordered in the previous HTP structure. This loop extends
      across the active-site cleft and appears to stabilize the dimer interface and the
      closed conformation by hydrogen-bonding. The present study will assist in the
      design of HTP inhibitors that could lead to drugs for anti-angiogenesis as well
      as for the potentiation of other nucleoside drugs.

PMID- 16803457
TI  - Conformational and functional characterization of trapped complexes of the P
      glycoprotein multidrug transporter.
AB  - The Pgp (P-glycoprotein) multidrug transporter couples ATP hydrolysis at two
      cytoplasmic NBDs (nucleotide-binding domains) to the transport of hydrophobic
      compounds. Orthovanadate (V(i)) and fluoroaluminate (AlF(x)) trap nucleotide in
      one NBD by forming stable catalytically inactive complexes (Pgp-M2+-ADP-X), which
      are proposed to resemble the catalytic transition state, whereas the complex
      formed by beryllium fluoride (BeF(x)) is proposed to resemble the ground state.
      We studied the trapped complexes formed via incubation of Pgp with ATP
      (catalytically forward) or ADP (reverse) and V(i), BeF(x) or AlF(x) using Mg2+ or
      Co2+ as the bivalent cation. Quenching of intrinsic Pgp tryptophan fluorescence
      by acrylamide, iodide and caesium indicated that conformational changes took
      place upon formation of the trapped complexes. Trapping with V(i) and ATP led to
      a 6-fold increase in the acrylamide quenching constant, K(SV), suggesting that
      large conformational changes take place in the Pgp transmembrane regions on
      trapping in the forward direction. Trapping with V(i) and ADP gave only a small
      change in quenching, indicating that the forward- and reverse-trapped complexes
      are different. TNP (trinitrophenyl)-ATP/TNP-ADP interacted with all of the
      trapped complexes, however, the fluorescence enhancement differed for the trapped
      states, suggesting a change in polarity in the nucleotide-binding sites. The
      nucleotide-binding site of the BeF(x)-trapped complex was much more polar than
      that of the V(i) and AlF(x) complexes. Functionally, all the trapped complexes
      were able to bind drugs and TNP-nucleotides with unchanged affinity compared with
      native Pgp.

PMID- 16803459
TI  - Separation and characterization of caveolae subclasses in the plasma membrane of
      primary adipocytes; segregation of specific proteins and functions.
AB  - Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary in
      size between 25 and 150 nm. They constitute sites of entry into the cell as well
      as platforms for cell signalling. We have previously reported that plasma
      membrane-associated caveolae that lack cell surface access can be identified by
      electron microscopy. We now report the identification, after density gradient
      ultracentrifugation, of a subclass of very high-density apparently closed
      caveolae that were not labelled by cell surface protein labelling of intact
      cells. These caveolae contained caveolin-1 and caveolin-2. Another class of high
      density caveolae contained caveolin-1, caveolin-2 and specifically fatty acid
      transport protein-1, fatty acid transport protein-4, fatty acyl-CoA synthetase,
      hormone-sensitive lipase, perilipin, and insulin-regulated glucose transporter-4.
      This class of caveolae was specialized in fatty acid uptake and conversion to
      triacylglycerol. A third class of low-density caveolae contained the insulin
      receptor, class B scavenger receptor-1, and insulin-regulated glucose transporter
      4. Small amounts of these proteins were also detected in the high-density
      caveolae. In response to insulin, the insulin receptor autophosphorylation and
      the amount of insulin-regulated glucose transporter-4 increased in these
      caveolae. The molar ratio of cholesterol to phospholipid in the three caveolae
      classes varied considerably, from 0.4 in very high-density caveolae to 0.9 in low
      density caveolae. There was no correlation between the caveolar contents of
      caveolin and cholesterol. The low-density caveolae, with the highest cholesterol
      concentration, were particularly enriched with the cholesterol-rich lipoprotein
      receptor class B scavenger receptor-1, which mediated cholesteryl ester uptake
      from high-density lipoprotein and generation of free cholesterol in these
      caveolae, suggesting a specific role in cholesterol uptake/metabolism. These
      findings demonstrate a segregation of functions in caveolae subclasses.

PMID- 16803460
TI  - Mapping of the interaction site of CP12 with glyceraldehyde-3-phosphate
      dehydrogenase from Chlamydomonas reinhardtii. Functional consequences for
      glyceraldehyde-3-phosphate dehydrogenase.
AB  - The 8.5 kDa chloroplast protein CP12 is essential for assembly of the
      phosphoribulokinase/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) complex from
      Chlamydomonas reinhardtii. After reduction of this complex with thioredoxin,
      phosphoribulokinase is released but CP12 remains tightly associated with GAPDH
      and downregulates its NADPH-dependent activity. We show that only incubation with
      reduced thioredoxin and the GAPDH substrate 1,3-bisphosphoglycerate leads to
      dissociation of the GAPDH/CP12 complex. Consequently, a significant twofold
      increase in the NADPH-dependent activity of GAPDH was observed. 1,3
      Bisphosphoglycerate or reduced thioredoxin alone weaken the association, causing
      a smaller increase in GAPDH activity. CP12 thus behaves as a negative regulator
      of GAPDH activity. A mutant lacking the C-terminal disulfide bridge is unable to
      interact with GAPDH, whereas absence of the N-terminal disulfide bridge does not
      prevent the association with GAPDH. Trypsin-protection experiments indicated that
      GAPDH may be also bound to the central alpha-helix of CP12 which includes
      residues at position 36 (D) and 39 (E). Mutants of CP12 (D36A, E39A and E39K) but
      not D36K, reconstituted the GAPDH/CP12 complex. Although the dissociation
      constants measured by surface plasmon resonance were 2.5-75-fold higher with
      these mutants than with wild-type CP12 and GAPDH, they remained low. For the D36K
      mutation, we calculated a 7 kcal.mol(-1) destabilizing effect, which may
      correspond to loss of the stabilizing effect of an ionic bond for the interaction
      between GAPDH and CP12. It thus suggests that electrostatic forces are
      responsible for the interaction between GAPDH and CP12.

PMID- 16803461
TI  - The betaI/betaIII-tubulin isoforms and their complexes with antimitotic agents.
      Docking and molecular dynamics studies.
AB  - Both microtubule destabilizer and stabilizer agents are important molecules in
      anticancer therapy. In particular, paclitaxel has been demonstrated to be
      effective for the treatment of ovarian, breast, and nonsmall cell lung
      carcinomas. It has been shown that emergence of resistance against this agent
      correlates with an increase in the relative abundance of tubulin isoform betaIII
      and that the more recently discovered IDN5390 can be effectively used once
      resistance has emerged. In this paper, we analyze the binding modes of these
      antimitotic agents to type I and III isoforms of beta-tubulin by computational
      methods. Our results are able to provide a molecular explanation of the
      experimental data. Using the same protocol, we could also show that no preference
      for any of the two isoforms can be detected for epothilone A, a potentially very
      interesting drug for which no data about the emergence of resistance is currently
      available. Our analysis provides structural insights about the recognition mode
      and the stabilization mechanism of these antimitotic agents and provides useful
      suggestions for the design of more potent and selective antimitotic agents.

PMID- 16803462
TI  - Vitiligo associated with other autoimmune diseases: polyglandular autoimmune
      syndrome types 3B+C and 4.
AB  - Vitiligo is a common skin disease characterized by depigmented maculae resulting
      from a reduction of the number and function of melanocytes. Many studies suggest
      that vitiligo might be an autoimmune disease. Vitiligo has been frequently
      described in association with other autoimmune diseases. Among the diseases
      described in association with vitiligo are the so-called autoimmune polyglandular
      syndromes (APS). Vitiligo can be present in all types of APS but the most
      frequent association appears to be in APS-3. APS-3 was defined as the association
      between autoimmune thyroiditis and another autoimmune disease. Here we report one
      patient with thyroiditis, vitiligo and autoimmune gastritis (APS-3B+C), one
      patient with chronic autoimmune thyroiditis, vitiligo and alopecia (APS-3C), and
      one case of a young patient with type 1 diabetes mellitus and vitiligo (APS-4),
      according to the newest classification. We stress the importance of a thorough
      assessment for autoimmune diseases in selected patients with vitiligo.

PMID- 16803463
TI  - Postinjury vascular intimal hyperplasia in mice is completely inhibited by CD34+
      bone marrow-derived progenitor cells expressing membrane-tethered anticoagulant
      fusion proteins.
AB  - BACKGROUND: Coagulation proteins promote neointimal hyperplasia and vascular
      remodelling after vessel injury, but the precise mechanisms by which they act in
      vivo remain undetermined. OBJECTIVES: This study, using an injury model in which
      the neointima is derived from bone marrow (BM)-derived cells, compared inhibition
      of tissue factor or thrombin on either BM-derived or existing vascular smooth
      muscle cells. METHODS: Two transgenic (Tg) mouse strains expressing membrane
      tethered tissue factor pathway inhibitor (TFPI) or hirudin (Hir) fusion proteins
      driven by an alpha smooth muscle actin (SMA) promoter were generated (alpha-TFPI
      Tg and alpha-Hir-Tg) and the phenotype after wire-induced endovascular injury was
      compared with that in wild-type (WT) controls. RESULTS: WT mice developed
      progressive neointimal expansion, whereas injury in either Tg was followed by
      repair back to a preinjured state. This was also seen when WT mice were
      reconstituted with BM from Tg mice but not when Tgs were reconstituted with WT
      BM, in which injury was followed by slowly progressive neointimal expansion.
      Injection of CD34+ cells from Tg mice into injured WT mice resulted in the
      accumulation of fusion protein-expressing cells from day 3 onwards and an absence
      of neointimal hyperplasia in those areas. CONCLUSIONS: Neointimal development
      after wire-induced endovascular injury in mice was completely inhibited when BM
      derived cells infiltrating the damaged artery expressed membrane tethered
      anticoagulant fusion proteins under an alpha-SMA promoter. These findings enhance
      our understanding of the pathological role that coagulation proteins play in
      vascular inflammation.

PMID- 16803465
TI  - Lymphocyte immunophenotype of circulating angioimmunoblastic T-cell lymphoma
      cells.

PMID- 16803464
TI  - Aprotinin is useful as a hemostatic agent in cardiopulmonary surgery: no.

PMID- 16803466
TI  - Images in haematology. Cervical mass after cytotoxic chemotherapy, secondary
      malignancy or epiphenomenon?

PMID- 16803467
TI  - The angiopoietin pathway is modulated by PAR-1 activation on human endothelial
      progenitor cells.
AB  - OBJECTIVES: The importance of protease-activated receptor-1 (PAR-1) in blood
      vessel development has been shown in knock-out mice. As endothelial progenitor
      cells (EPCs) express functional PAR-1, we examined whether PAR-1 stimulation by
      the peptide SFLLRN interfered with the angiopoietin pathway, that is EPC
      commitment, proliferation and migration. METHODS AND RESULTS: Given the strong
      PAR-1 expression on CD34+ cells, we tested the effect of SFLLRN 75 micromol L(-1)
      on the emergence of EPCs from cord blood. PAR-1 activation did not modify the
      number of colonies or the day of emergence, in keeping with the lack of induction
      of angiopoietin 1 gene expression. Conversely, SFLLRN treatment of EPCs induced
      angiopoietin 2 gene expression and protein synthesis. Experiments with polyclonal
      blocking antibodies showed that angiopoietin 2 was involved in the proliferative
      effect of PAR-1 activation. PAR-1 activation also enhanced migration toward
      angiopoietin 1 in a Boyden chamber assay. CONCLUSIONS: Our study demonstrates
      that PAR-1-induced proliferation of EPCs involves angiopoietin 2. PAR-1 also
      enhances EPC migration toward angiopoietin 1. These findings might explain the
      role of thrombin in neovascularization via the angiopoietin pathway.

PMID- 16803468
TI  - Which drugs cause preventable admissions to hospital? A systematic review.
AB  - AIMS: Previous systematic reviews have found that drug-related morbidity accounts
      for 4.3% of preventable hospital admissions. None, however, has identified the
      drugs most commonly responsible for preventable hospital admissions. The aims of
      this study were to estimate the percentage of preventable drug-related hospital
      admissions, the most common drug causes of preventable hospital admissions and
      the most common underlying causes of preventable drug-related admissions.
      METHODS: Bibliographic databases and reference lists from eligible articles and
      study authors were the sources for data. Seventeen prospective observational
      studies reporting the proportion of preventable drug-related hospital admissions,
      causative drugs and/or the underlying causes of hospital admissions were
      selected. Included studies used multiple reviewers and/or explicit criteria to
      assess causality and preventability of hospital admissions. Two investigators
      abstracted data from all included studies using a purpose-made data extraction
      form. RESULTS: From 13 papers the median percentage of preventable drug-related
      admissions to hospital was 3.7% (range 1.4-15.4). From nine papers the majority
      (51%) of preventable drug-related admissions involved either antiplatelets (16%),
      diuretics (16%), nonsteroidal anti-inflammatory drugs (11%) or anticoagulants
      (8%). From five studies the median proportion of preventable drug-related
      admissions associated with prescribing problems was 30.6% (range 11.1-41.8), with
      adherence problems 33.3% (range 20.9-41.7) and with monitoring problems 22.2%
      (range 0-31.3). CONCLUSIONS: Four groups of drugs account for more than 50% of
      the drug groups associated with preventable drug-related hospital admissions.
      Concentrating interventions on these drug groups could reduce appreciably the
      number of preventable drug-related admissions to hospital from primary care.

PMID- 16803469
TI  - Human papillomavirus testing as an optional screening tool in low-resource
      settings of Latin America: experience from the Latin American Screening study.
AB  - Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was
      carried out in a cohort of 4284 women at their first clinical visit. Overall
      prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20
      years to only 11.0% among those older than 41 years. HPV prevalence was
      significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1
      1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6
      2.4), and those women with two or more sexual partners during the past 12 months
      prior to examination (OR = 1.6; 95% CI 1.2-2.2). HPV detection increased in
      parallel with increasing cytologic abnormality, being highest in women with high
      grade squamous intraepithelial lesion (P= 0.001). Specificity of the HPV test in
      detecting histologically confirmed cervical disease was 85% (95% CI 83.9-86.1).
      Sensitivity of the HPV test in detecting histologic abnormalities increased in
      parallel with disease severity, ranging from 51.5% for cervical intraepithelial
      neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective
      decline of positive predictive value. These data suggest that HPV testing with HC
      II assay might be a viable screening tool among this population with relatively
      high prevalence of cervical disease.

PMID- 16803470
TI  - Prediction of lymph node metastases in vulvar cancer: a review.
AB  - The aim of this study was to review the literature on currently available non-
      and minimally-invasive diagnostic methods and analysis of primary tumor
      characteristics for prediction of inguinofemoral lymph node metastases in
      patients with primary squamous cell carcinoma of the vulva. We used the English
      language literature in PubMed and reference lists from selected articles. Search
      terms included vulvar carcinoma, prognosis, lymph node metastases, ultrasound,
      computer tomography, magnetic resonance imaging, positron emission tomography,
      and sentinel lymph node. No study type restrictions were imposed. Currently no
      noninvasive imaging techniques exist that are able to predict lymph node
      metastases with a high enough negative predictive value. A depth of invasion < or
      =1 mm is the only histopathologic parameter that can exclude patients for
      complete inguinofemoral lymphadenectomy. No other clinicopathologic parameter
      allows exclusion of lymph node metastases with a high enough negative predictive
      value. The minimally invasive sentinel node procedure is a promising technique
      for selecting patients for complete lymphadenectomy, but its safety has not been
      proven yet.

PMID- 16803471
TI  - A review of the pathology and management of uterine papillary serous carcinoma
      and correlation with outcome.
AB  - Uterine papillary serous carcinoma (UPSC) accounts for 10% of endometrial
      carcinomas but a higher proportion of deaths due to its aggressive nature and
      poor response to chemotherapy and radiotherapy. In order to add to the knowledge
      of UPSC in the literature and to review our local practices, we examined the
      pathology, medical records, and management of all cases of UPSC (67 patients)
      treated in South East Scotland over a 10-year period and also evaluated the
      prognostic significance of the percentage of UPSC in endometrial pipelle and
      hysterectomy specimens. Although only 63% of initial diagnostic biopsies were
      reported to contain UPSC, rereview of the cases revealed UPSC in 98.5% of the
      preoperative biopsies. The percentage of UPSC in the tumors did not affect the
      outcome. Stage, positive omentum, and treatment with external-beam +/-
      intracavitary radiotherapy were significantly correlated with overall survival
      and progression-free survival by univariate analysis, but only stage (P < 0.01)
      was correlated with outcome on multivariate analysis. Chemotherapy did not affect
      outcome. UPSC may be difficult to diagnose in preoperative biopsies, particularly
      when present as part of a mixed tumor. Even a small percentage of UPSC in a
      diagnostic biopsy or hysterectomy specimen is correlated with a poor prognosis.
      This study emphasizes the need of a cooperative, prospective study on this
      distinct uterine carcinoma.

PMID- 16803472
TI  - Genetic variation in ABCB1 influences paclitaxel pharmacokinetics in Japanese
      patients with ovarian cancer.
AB  - Paclitaxel, an antineoplastic agent used for the treatment of ovarian cancer, is
      metabolized by cytochrome P450 (CYP)3A4 and CYP2C8 and is excreted from cells by
      ATP-binding cassette (ABCB1) (multi-drug resistance [MDR1], P-glycoprotein).
      Expression of these proteins is regulated by pregnane X receptor (PXR). Although
      there are common genetic polymorphisms in the genes encoding these proteins,
      their effect on the clinical efficacy of paclitaxel is unclear. We therefore
      examined the relationship of the paclitaxel pharmacokinetics in 13 patients with
      ovarian cancer to polymorphisms in CYP2C8, CYP3A5, ABCB1, and PXR. We found high
      interindividual variability in the plasma concentrations of two metabolites,
      6alpha-hydroxypaclitaxel and p-3'-hydroxypaclitaxel. All the patients were
      genotyped as CYP2C8*1/*1. Neither the CYP3A5 A6986G (CYP3A5*3) nor the PXR C
      25385T alleles were associated with altered plasma concentrations of paclitaxel
      and its metabolites. ABCB1 T-129C, T1236C, and G2677(A,T), however, was
      associated with lower area under the plasma concentration-time curve (AUC) of
      paclitaxel. We also observed a significant correlation between the AUC (r=-0.721)
      or the total clearance of paclitaxel (CL(tot)) (r= 0.673) and the ABCB1 mutant
      allele dosage in each patient. Taken together, our findings suggest that
      interindividual variability in paclitaxel pharmacokinetics could be predicted by
      ABCB1 genotyping.

PMID- 16803473
TI  - Prognostic significance of tumor necrosis in ovarian cancer patients treated with
      neoadjuvant chemotherapy and interval surgical debulking.
AB  - The objective of this study was to study the significance of tumor necrosis
      documented at the time of interval surgical debulking after neoadjuvant
      chemotherapy. Retrospective chart reviews were carried out from 1997 to 2005 to
      identify ovarian cancer patients treated with neoadjuvant chemotherapy. Patients'
      demographics together with disease characteristics, treatment-related variables,
      and outcomes were recorded. Cox proportional hazard models were built to model
      time to progression using predictor variables such as age, cancer stage, tumor
      grade, residual disease, percentage change in CA125 level from baseline, and
      degree of necrosis in resected tumor specimens. One hundred one patients were
      included in the study. Optimal debulking was achieved in 74% of the patients. Cox
      regressions revealed three significant predictive variables of time to first
      progression: younger age (hazard ratio [HR] = 0.95, 95% CI 0.92-0.98, P= 0.004),
      residual disease (P= 0.048), and the absence/minimal tumor necrosis after three
      cycles of neoadjuvant chemotherapy (HR = 1.97, 95% CI 1.01-3.87, P= 0.048). The
      estimated median survival was 50.66 months (95% CI 46.12-55.20). The lack of or
      minimal tumor necrosis after neoadjuvant chemotherapy is an independent risk
      factor for recurrent disease.

PMID- 16803474
TI  - Extraperitoneal laparoscopic para-aortic lymphadenectomy for lymph node
      recurrence of fallopian tube carcinoma.
AB  - The endoscopic retroperitoneal approach is a minimally invasive method for
      surgical staging of cervical cancer. A 57-year-old woman had an intraoperative
      diagnosis of carcinoma of the left fallopian tube and undergone a retroperitoneal
      pelvic and para-aortic lymphadenectomy with no peritonization during surgical
      staging. Small suspicious nodes in the serous membrane of the sigmoid colon and
      peritoneal washings were positive for malignancy. A total of 12 nodes were
      obtained, all of which were negative. She received six cycles of paclitaxel and
      platinum-based chemotherapy and showed a complete clinical response. Thirty-two
      months after surgery, the abdominal computed tomography scan showed a left para
      aortic lymph node, 19 mm in diameter, which was successfully removed through an
      extraperitoneal laparoscopic approach. The extraperitoneal laparoscopic approach
      of the para-aortic region is a feasible procedure after previous transperitoneal
      lymphadenectomy and chemotherapy.

PMID- 16803475
TI  - Brain metastases as isolated site of relapse in patients with epithelial ovarian
      cancer previously treated with platinum and paclitaxel-based chemotherapy.
AB  - Brain metastases in patients with epithelial ovarian cancer (EOC) have an
      estimated incidence of 0.3-1.9% and are isolated in up to 50% of these patients.
      The risk factors and the prognostic significance of isolated central nervous
      system (CNS) relapse in patients with EOC who received primary treatment with
      platinum and paclitaxel have not been identified. We conducted a retrospective
      study in patients with EOC who relapsed with isolated brain metastases and report
      our experience. Two hundred sixty-seven patients with stages III and IV EOC, in
      clinical complete remission after first-line treatment with platinum and
      paclitaxel, were included in our analysis. After a median follow-up of 65 months,
      150 patients had relapsed. Eight patients (5%) had isolated brain metastases.
      Patient and disease characteristics did not differ among patients who relapsed
      with isolated brain metastases and those with relapse outside the CNS. Median
      time to first disease relapse, overall survival, and survival after relapse did
      not differ significantly between patients with brain metastases and those with
      relapse outside the CNS. Two patients have died 6 and 12 months after the
      diagnosis of brain metastases, and 5 patients are alive 4-35 months after the
      diagnosis of isolated brain metastases. Three patients remain free of disease 4
      18 months after treatment with radiotherapy and systemic chemotherapy for their
      CNS metastatic disease. Patients with isolated brain metastases have comparable
      survival to patients with relapse outside the CNS, and long-term remission can be
      achieved in some cases, provided that systemic chemotherapy is added to local
      treatment.

PMID- 16803476
TI  - Relationship between p53-associated proteins and estrogen receptor status in
      ovarian serous neoplasms.
AB  - We studied the immunoexpression of p14ARF, MDM2, and p53, in addition to
      relationships between those protein expressions and estrogen receptor (ER)alpha
      in ovarian serous tumors including benign (n= 23), borderline (n= 41), and
      malignant (n= 94). The aberrant expressions of p14ARF, MDM2, and p53 were
      observed in 19.6% (31/158), 47.5% (75/158), and 39.9% (63/158) of cases,
      respectively. The expression of MDM2 was significantly higher in borderline
      tumors compared to benign (P= 0.04) and malignant (P < 0.01) tumors. p53
      expression in borderline tumors was uncommon, and p14ARF expression loss was
      mainly observed in carcinomas. Altered expression of p14ARF, MDM2, and p53 shows
      significant relationship with stage. Overexpression of MDM2 (P= 0.01) and loss of
      p14ARF expression (P= 0.04) were significantly associated with ER expression. Our
      results suggest that alteration of p14ARF-MDM2-p53 pathway proteins may
      contribute significantly to the tumorigenesis of ovarian serous neoplasms, and ER
      is involved in cellular regulation of p14ARF-MDM2-p53 pathway in ovarian serous
      neoplasms.

PMID- 16803477
TI  - The evaluation of human papillomavirus DNA testing in primary screening for
      cervical lesions in a large Japanese population.
AB  - To examine the utility of human papillomavirus (HPV) DNA testing for the
      screening of cervical cancer and its precursors, a prospective cohort study was
      performed in which a total of 8156 women with a median age of 36 years were
      enrolled. Two smear samples scraped from the uterine cervix were served for
      Papanicolaou test and HPV DNA testing (Hybrid Capture-II system). HPV-positive
      samples were further examined for HPV subtype using a DNA microarray chip. Women
      with cytologic abnormality or those with high-risk HPV DNA were further examined
      by colposcopy to determine histologic diagnosis. High-risk HPV DNA was detected
      in 11% of the general population, with higher prevalence of specific types,
      including 52, 16, 58, 51, 56, and 18. As expected, younger women were likely to
      have increased frequency of HPV infection. Notably, HPV DNA testing detected all
      45 cases of cervical intraepithelial neoplasia (CIN) 3, while cytologic findings
      were negative in 6 of these cases. It is of particular interest that CIN was
      commonly associated with multiple HPV types, while invasive cancers had a single
      type of HPV. In terms of both sensitivity and positive predictive value in
      detecting the CIN, HPV DNA testing is superior to cytology. However, most
      importantly, HPV DNA testing in combination with cytology significantly improved
      the efficacy to CIN screening.

PMID- 16803478
TI  - Implications regarding atypical squamous cells of undetermined significance among
      women residing in a US-Mexico border city.
AB  - We conducted a study of Mexican American women living in a US-Mexico border city
      who attended a gynecology clinic for Papanicolaou (Pap) smear. The objective of
      this study was to describe the cytologic outcomes of women who had atypical
      squamous cells of undetermined significance (ASCUS) diagnosis after a Pap smear
      and to observe any changes during follow-up colposcopy. A total of 852 abnormal
      Pap smear were identified through a computer search for a 6-month period.
      Histology data were available for 317 cases. Benign findings were observed in
      45.4% of cervical biopsies. A clinically significant diagnosis was reported in
      the remaining tissue sample. The diagnosis report was either single or combined
      and recorded as follows: human papilloma virus 46.3%, cervical intraepithelial
      neoplasia (CIN) 1, 23.6%; CIN 2, 5.6%; and CIN 3, 1.5%. There was one case of
      invasive cervical cancer. Overall, the incidence rate of ASCUS was 5%. However,
      we found that a significant proportion of this population had CIN 1 through CIN
      3. Furthermore, this population has traditionally been noncompliant and routinely
      failed to attend follow-up appointments. Based on these results, the clinician
      should not ignore an initial abnormal Pap smear. Therefore, it is not
      unreasonable to perform colposcopy in Mexican American patients with a first time
      diagnosis of ASCUS on routine Pap smear.

PMID- 16803479
TI  - Human papillomavirus genotype prevalence in cervical biopsies from women
      diagnosed with cervical intraepithelial neoplasia or cervical cancer in
      Melbourne, Australia.
AB  - Multicenter international phase III clinical trials using multivalent human
      papillomavirus (HPV) vaccines for cervical cancer (CC) prevention are underway.
      As HPV immunity is type specific, defining HPV genotype prevalence in different
      regions to ascertain whether predominant types differ geographically is
      considerably important prior to vaccine implementation. This study aimed to
      define HPV genotypes present in CC and high-grade dysplasia among women in
      Melbourne, Australia. HPV genotype analysis of a cross section of women in
      Melbourne with cervical dysplasia/cancer was performed. A total of 493 cervical
      biopsies from patients being treated for moderate (n= 122) or severe (n= 180)
      cervical intraepithelial neoplasia (CIN II/III) or CC (n= 191) were tested for
      HPV genotypes using the PGMY09/11 primer system and line blot assay. HPV
      detection rates were 63.9%, 72.8%, and 86.9% in CIN II, CIN III, and CC biopsies,
      respectively. The most prevalent HPV genotypes among CC biopsies were HPV-16
      (52.9%), HPV-18 (18.3%), HPV-45 (6.3%), HPV-39 (3.1%), and HPV-73 (2.6%).
      Multiple HPV infections, comprising two to five types, were identified in 14.4%
      of biopsies, being significantly fewer (5.2%) among CC biopsies (P < 0.0001).
      These results indicate that the two most prevalent CC-associated HPV genotypes in
      Australia parallel those described internationally, with type variations
      thereafter.

PMID- 16803480
TI  - Prevalence of human papillomavirus types 16 and 18 in cervical adenocarcinoma and
      its precursors in Scottish patients.
AB  - Our aim was to determine the prevalence of human papillomavirus (HPV) types 16
      and 18 in cervical adenocarcinoma (and its precursors) in Scottish patients.
      Nucleic acid was extracted from paraffin-embedded, formalin-fixed tissues. We
      examined 119 cases of invasive adenocarcinoma, 20 cases of adenocarcinoma in
      situ, and 16 cases of normal glandular epithelium. HPV DNA was detected by
      polymerase chain reaction using type-specific primers for the E6 and E7 genes of
      HPV-16 and HPV-18 with conformation of HPV genotype by subsequent restriction
      fragment length polymorphism. HPV DNA was identified in 87 (62.6%) cases, with
      HPV-16 being detectable in 65 (47%) cases and HPV-18 in 41 (29%) cases. All the
      cases of normal tissue tested negative for HPV-16 and/or HPV-18. No significant
      relation between infecting HPV type (16 or 18) and subtypes of disease (within
      the invasive category and between the preinvasive and the invasive categories)
      was noted. Our findings support that HPV-16, along with HPV-18, are likely to
      play a significant role in the pathogenesis of cervical adenocarcinomas and that
      cervical cancer screening strategies that incorporate oncogenic HPV testing, and
      prophylactic vaccines that target these types, will be beneficial for the
      reduction of adenocarcinoma and associated glandular precursors.

PMID- 16803481
TI  - Serologic response to human papillomavirus 16 among Australian women with high
      grade cervical intraepithelial neoplasia.
AB  - This study evaluated the detection of human papillomavirus (HPV) 16 antibody in
      HPV 16-associated cervical intraepithelial neoplasia (CIN) in Australian women.
      Seroreactivity to HPV 16 L1 virus-like particles was assessed in patients with
      CIN 2 (n= 169) and CIN 3 (n= 229) lesions previously tested for the presence of
      HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA
      positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or
      with HPV of types other than 16 in the lesion (43/167) (P= 0.0004). In addition,
      seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229)
      of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than
      CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most
      common in women with HPV 16-associated CIN, but many patients with HPV-associated
      CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN
      associated with other HPV types. Overall, HPV 16 serology is a poor predictor of
      presence of HPV 16-associated CIN 3 in patient population studied.

PMID- 16803482
TI  - Reduction in prevalence of invasive cervical cancer in KwaZulu-Natal, South
      Africa: impact of the human immunodeficiency virus epidemic.
AB  - The bulk of the human immunodeficiency virus (HIV) pandemic continues to ravage
      the developing world, especially sub-Saharan countries. The HIV seroprevalence
      among women with invasive cervical cancer varies in different parts of the world.
      A comparison of women with cervical cancer was undertaken for epidemiologic data
      in the province of KwaZulu-Natal, South Africa, which has the highest HIV
      prevalence. The two time periods of study were 1999 and 2003. The aim was to
      determine the trends of prevalence of invasive cervical cancer and HIV infection
      among such women. While the background prevalence of HIV infection among women
      with invasive cervical cancer in our setting has remained constant over the two
      time periods (21% and 21.8%), there has been a significant reduction in the
      number of women presenting with invasive cervical cancer to our center (672 to
      271) over the two time periods, with no changes in other variables. On the
      contrary, the prevalence of HIV infection among antenatal attendees had risen
      from 32.5% to 38.5% in the 1999 and 2003 periods, respectively. Reasons for this
      dramatic trend are presented together with other epidemiologic data.

PMID- 16803483
TI  - Human papillomavirus-specific viral types are common in Mexican women affected by
      cervical lesions.
AB  - Cervical cancer (CC) is the most common in Mexican female population. The human
      papillomavirus (HPV) 16 and 18 frequencies in worldwide may be different due to
      geographical distribution. We analyzed the prevalence of HPV types and
      determinated their association in cervical lesion in a Mexican population. One
      hundred fifty-nine normal cervical smears, 95 low-grade squamous intraepithelial
      lesions (LGSIL), 59 high-grade squamous intraepithelial lesions (HGSIL), and 108
      CC samples of the patients were collected. HPV types were determined by
      sequencing. We detected 11 high-risk types, four low-risk types, three not
      determinated, and two probably high risk. HPV were present in 12%, 57%, 88%, and
      92% from normal, LGSIL, HGSIL, and CC samples, respectively. HPV 16 was the most
      common in all cervical lesions (71.6% in CC). HPV 58 was present in 18.6% of
      HGSIL, and the HPV 18 in 4.6% of CC. The 76% of all detected viruses belong to A9
      species branch. Control women showed high percentage of HPV high-risk infection,
      suggesting that this is a high-risk group. High frequency of HPV 16 compared with
      a low incidence of HPV 18 was observed. HPV 58 is frequently detected in HGSIL
      but low frequency is found in CC. These findings might be considered for HPV
      screening.

PMID- 16803484
TI  - Human papillomavirus prevalence in postradiotherapy uterine cervical carcinoma
      patients: correlation with recurrence of the disease.
AB  - To understand the role of human papillomavirus (HPV) in recurrence of uterine
      cervical cancer (CA-CX) after radiotherapy, we have analyzed the HPV prevalence
      in the exfoliated cells of 56 patients and their corresponding plasma. HPV DNA
      was detected in exfoliated cells of 78% (44/56) patients (HPV-16, 68%; HPV-18,
      14%; HPV-X [other than 16, 18], 11%; and mixed infection of HPV-16 and HPV-18 in
      three cases). HPV DNA in plasma was present in only 25% (11/44) of the HPV
      positive exfoliated cells (positive predictive value, 100%; negative predictive
      value, 27%) with concordance in HPV types. The recurrence of the disease was
      significantly associated with the presence of HPV in the exfoliated cell (P=
      0.01) and plasma (P= 0.007) as well as high viral load in the exfoliated cell (P=
      0.0002). Kaplan-Meier disease-free estimates have also shown the significant
      association between HPV prevalence in plasma and recurrence of the disease (P=
      0.045). Thus, it indicates that in postradiotherapy CA-CX patients, the high
      viral load in the exfoliated cell as well as HPV presence in the plasma samples
      could be used in early detection of the patients at increased risk for disease
      recurrence and progression.

PMID- 16803485
TI  - Prediction of high-grade cervical disease with human papillomavirus detection in
      women with glandular and squamous cytologic abnormalities.
AB  - The objective of this study was to assess whether human papillomavirus (HPV)
      detection with hybrid capture II (HC II) can help predict the presence and the
      nature, glandular or squamous, of histologic cervical lesions in women referred
      due to atypical glandular cells (AGC) or high-grade squamous intraepithelial
      lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised
      AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and
      HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a
      histologic assessment of their cervix. Histologic analysis showed 38 women with
      (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%)
      glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost
      70% of AGC-HPV-negative patients did not have a pathologically proven cervical
      neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with
      a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC
      HSIL were of squamous nature, and HPV detection did not contribute to their
      differentiation from glandular lesions. We conclude that in women with AGC, HPV
      positivity strongly correlated with the presence of glandular or squamous
      cervical lesion but did not help distinguishing women with squamous from those
      with glandular neoplasia.

PMID- 16803486
TI  - An appraisal of the level of awareness and utilization of the Pap smear as a
      cervical cancer screening test among female health workers in a tertiary health
      institution.
AB  - Papanicolaou (Pap) smear test is considered the best approach to reduce cervical
      cancer incidence worldwide. We surveyed 195 female health workers with structured
      questionnaires to identify factors that could influence the awareness and
      utilization of the Pap smear as a cervical cancer screening test. More than 65%
      of the respondents were aware of the disease, cervical cancer, and approximately
      64% were aware of the Pap smear test. Seven three (39.7%) of the respondents had
      their sexual debut (coitarche) before the age of 20 years, while 109 (59.9%) have
      had multiple sexual partners. The modal number of sexual partners was 3, range 0
      8. Pap smear awareness level significantly varied among the categories of the
      female health workers (P < 0.001). A minority of 14.1% have had a Pap test. There
      was a significant variation in utilization of Pap test across the various
      categories of the health workers (Pearson Chi-square 14.67, P < 0.05), and a
      significant correlation between Pap smear awareness and utilization (P < 0.001).
      The majority, 89%, believed that they were not at risk of developing cervical
      cancer. The self-reported utilization of Pap test among health workers was low.
      While there was a positive correlation between Pap test awareness and
      utilization, screening uptake was very poor due to a combination of inappropriate
      beliefs, misapprehension, and deficient knowledge. There is an urgent need for an
      aggressive awareness campaign and the provision of a screening program
      nationally.

PMID- 16803487
TI  - Normal appearing endometrial cells in cervical smears of asymptomatic
      postmenopausal women have predictive value for significant endometrial pathology.
AB  - The objective of this study was to determine whether postmenopausal asymptomatic
      women with normal endometrial cells in their smear are at higher risk for
      endometrial pathology compared with women without these cells. Histologic follow
      up outcome and otherwise cytologic follow-up of 29,144 asymptomatic
      postmenopausal women was determined. Presence of normal endometrial cells, age,
      use of hormones, and reported elevated maturation index were assessed. The effect
      of each variable on outcome as well as the combined effect were evaluated.
      Prevalence rate of (pre)malignant uterine disease was significantly higher when
      normal endometrial cells were found in the cervical smear (6.5%) as compared to
      smears without these cells (0.2%), resulting in a relative risk of 40.2 (95% CI
      9.4-172.2). Neither age nor hormone use or elevated maturation index showed
      significant impact on the outcome. Asymptomatic postmenopausal women with normal
      endometrial cells in their smear are at significant higher risk for
      (pre)cancerous endometrial lesion than women without these cells. These cases
      should be reported to the physician with an explicit comment that normal
      endometrial cells in a smear of a postmenopausal woman is an abnormal finding,
      possibly associated with significant endometrial pathology. It raises the
      question whether further gynecological examination would be more appropriate.

PMID- 16803488
TI  - Prime-boost vaccination strategy in women with high-grade, noncervical anogenital
      intraepithelial neoplasia: clinical results from a multicenter phase II trial.
AB  - The objective of this study was to determine the clinical effectiveness of a
      prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II
      prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital
      intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a
      recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one
      dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV).
      Clinical responses were evaluated by serial photographs, symptomatology, and
      biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with
      vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia
      grade 3. Clinical responses were seen in five women (17%), with one complete and
      five partial responses. Fifteen women (62%) had symptomatic improvement. No
      serious adverse effects were recorded. This is the first trial of a prime-boost
      vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV)
      in the management of AGIN. Since the prime-boost approach in this cohort offered
      no significant advantages over single TA-HPV vaccination, there are no further
      studies planned using this protocol. Future studies are warranted to define
      responders to immunotherapy.

PMID- 16803489
TI  - Outcomes of loop electrosurgical excision procedure for cervical neoplasia in
      human immunodeficiency virus-infected women.
AB  - The objective of this study was to evaluate the treatment outcomes and
      complications in human immunodeficiency virus (HIV)-infected women undergoing
      loop electrosurgical excision procedure (LEEP) for cervical neoplasia. The
      medical record of 60 evaluable HIV-infected women who had abnormal Papanicolaou
      (Pap) smear and underwent LEEP following colposcopy at Chiang Mai University
      Hospital between May 1998 and June 2004 was reviewed. Thirty-one (51.7%) had
      associated genital infection at screening. Twenty-five (41.7%) had opportunistic
      infection, but only 18 (30.0%) were treated with antiretroviral therapy. The most
      common abnormal Pap smear was high-grade squamous intraepithelial lesion (46.7%),
      followed by low-grade squamous intraepithelial lesion (40.0%). Forty (66.7%)
      women had clear surgical margins after LEEP. Only one (1.7%) woman had severe
      intraoperative hemorrhage. Early and late postoperative hemorrhage were noted in
      three (5%) women of each period. Localized infection of the cervix was detected
      in seven (11.7%) women. Two (3.3%) women developed cervical stenosis at 6 months
      after LEEP. There was no significant difference in overall complications between
      HIV-infected women and the control group (P= 0.24). Among 60 HIV-infected women,
      no statistical difference in the rate of margins involvement (P= 1.00) and
      complications (P= 0.85) could be demonstrated between HIV-infected women who
      received antiretroviral therapy and those who did not. Disease-free rate at 6 and
      12 months were 97.1% and 88%, respectively. These data demonstrated that LEEP
      appears to be safe and effective in HIV-infected women.

PMID- 16803490
TI  - Psychologic morbidities prior to loop electrosurgical excision procedure in the
      treatment of cervical intraepithelial neoplasia.
AB  - The objective of this study was to assess and compare anxiety and distress in
      patients undergoing colposcopic examinations and loop electrosurgical excision
      procedure (LEEP). Patients seen for evaluation of cervical intraepithelial
      neoplasia (CIN) and LEEP were recruited. All patients received further teaching
      with respect to their abnormality right after the colposcopic evaluation by
      nursing staff. The Hospital anxiety and Depression Scale (HADS) and the
      Psychosocial Effects of Abnormal Pap Smears (PEAPS) questionnaires were used to
      measure and compare distress between the two groups. Linear regression models
      were built to identify significant predictive variables for psychologic
      morbidities. Twenty-one colposcopy and 20 LEEP patients participated in this
      study. No significant demographic differences were noted. Eighty-one percent of
      patients having colposcopy and 65% of those undergoing LEEP can be classified as
      having significant anxiety and depression based on the HADS questionnaire.
      Patients undergoing LEEP scored significantly better than colposcopy patients on
      the mean total PEAPS score and on the self-belief/cancer concern and effects on
      sexual relationship dimension scores. Significant psychologic morbidities exist
      in patients diagnosed with CIN. Face-to-face individualized education and support
      after colposcopy can decrease patients' distress at subsequent treatment visits.

PMID- 16803492
TI  - High-dose rate brachytherapy in the treatment of carcinoma of uterine cervix:
      twenty-year experience with cobalt after-loading system.
AB  - This retrospective analysis aims to report results of patients with cancer of
      uterine cervix treated with external-beam radiotherapy (EBR) and high-dose rate
      (HDR) brachytherapy, using manual treatment planning. From 1975 to 1995, 237
      patients with FIGO stages IIB-IVA and mean age of 54.31 years were treated. EBR
      dose to the whole pelvis was 50 Gy in 25 fractions. Brachytherapy with HDR after
      loading cobalt source (Cathetron) was performed following EBR completion with a
      dose of 30 Gy in three weekly fractions of 10 Gy to point A. Survival, local
      control, and genitourinary and gastrointestinal complications were assessed. In a
      median follow-up of 60.2 months, the 10-year overall and disease-free survival
      rate was 62.4%. Local recurrence was seen in 12.2% of patients. Distant
      metastases to the lymph nodes, peritoneum, lung, liver, and bone occurred in
      25.3% of patients. Less than 6% of patients experienced severe genitourinary
      and/or gastrointestinal toxicity that were relieved by surgical intervention. No
      treatment-related mortality was seen. This series suggests that 50 Gy to the
      whole pelvis together with three fractions of 10 Gy to point A with HDR
      brachytherapy is an effective fractionation schedule in the treatment of locally
      advanced cancer of cervix. To decrease the complications, newer devices and
      treatment planning may be beneficial.

PMID- 16803491
TI  - The role of pretreatment squamous cell carcinoma antigen level in locally
      advanced squamous cell carcinoma of the uterine cervix treated by radiotherapy.
AB  - The purpose of this study was to determine the pretreatment serum squamous cell
      carcinoma antigen (SCC-ag) level as a generally applicable measurement in
      predicting and estimating the treatment outcome of patients with locally advanced
      SCC of the cervix. Three hundred fifty-two patients with stage IIB-IVA SCC of the
      cervix were managed with both external irradiation and high-dose rate
      intracavitary brachytherapy. A significantly higher median SCC-ag was seen in
      association with increasing stage, tumor size, and lymph node involvement. The
      difference in disease-free survival (DFS) between stages IIB and III patients was
      not statistically significant with SCC-ag level <2 ng/mL. In multivariate
      analysis, median SCC-ag level (> or =6.0 ng/mL) and lymph node metastases had
      significant independent effects on absolute survival and DFS. A direct linear
      relationship (y=-2.932x+ 84.896) existed between the median SCC-ag of groups
      distributed by pretreatment prognostic factors and the 5-year DFS rate. The 5
      year DFS rate as a function of SCC-ag level defined by cervix size, lymph node
      status, and hydronephrosis was obtained from a formula combining risk scores and
      the baseline survival function. From the obtained formulas, we can objectively
      estimate the treatment outcome in patients with locally advanced squamous cell
      cervical cancer.

PMID- 16803493
TI  - Time course and outcome of central recurrence after radiation therapy for
      carcinoma of the cervix.
AB  - We investigated the time course of central disease recurrence (CDR) in 2997
      patients treated with radiation for stage I-II squamous cell carcinoma of the
      cervix. CDR rates were 6.8%, 7.8%, and 9.6%, at 5, 10, and 20 years,
      respectively. The risk of CDR was independently correlated with tumor size (P <
      0.0001) but not with FIGO stage. The hazard rate peaked in the first year of
      follow-up and then fell steeply; after 3 years, the hazard rate was approximately
      constant at 0.2-0.4% per year. Although after 3 years the risk of CDR was low, it
      continued to be slightly greater for patients with tumors > or =5 cm than for
      those with smaller tumors (P= 0.001). Patients who had CDR < 36 months after
      treatment were less likely to be candidates for salvage therapy and had a poorer
      post-recurrence survival rate than those with recurrence > or =36 months after
      treatment (4.5% versus 42.1%, P < 0.0001). The higher rate of CDR in the first 3
      years and the poor survival after early recurrence suggest that most early CDRs
      are true relapses. The relatively stable annual actuarial risk between 3 and 25
      years and the better survival rate after late CDR suggest that most "recurrences"
      after 3 years are actually new neoplasms.

PMID- 16803494
TI  - Postoperative radiation therapy improves prognosis in patients with adverse risk
      factors in localized, early-stage cervical cancer: a retrospective comparative
      study.
AB  - The objective of this study was to assess the role of postoperative radiotherapy
      (RT) in early-stage cervical carcinoma with risk factors other than positive
      nodes, parametrial invasion, or positive margins and to compare outcomes using
      the Leiden University Medical Center (LUMC) modification of the Gynecologic
      Oncology Group (GOG) system with the GOG prognostic scoring system itself.
      Between January 1984 and April 2005, 402 patients with early-stage cervical
      cancer underwent radical hysterectomy. A total of 51 patients (13%) had two of
      the three risk factors and had pathologic tumor size (> or =40 mm), invasion (>
      or =15 mm), and capillary lymphatic space involvement, and were identified as the
      so-called high-risk (HR). We compared 34 patients who received RT based on the
      LUMC risk profile (67%) with 17 who did not (33%). The GOG score was calculated
      as well. We compared the GOG scores within the LUMC risk groups: HR+ (two out of
      three risk factors) and HR- (less than two out of three risk factors).
      Differences in 5-year cancer-specific survival (CSS) and 5-year disease-free
      survival (DFS) between the HR group treated with RT (86%, 85%) and without RT
      (57%; 43%) were statistically significant. The LUMC criteria did not
      significantly differ from the GOG risk profile, concerning recurrence, CSS, and
      DFS. HR patients benefit from adjuvant RT. The LUMC modification of the GOG
      system seems to be simpler and has a slightly higher threshold for the indication
      for RT but without a difference in outcome.

PMID- 16803495
TI  - An observational longitudinal study to evaluate miction, defecation, and sexual
      function after radical hysterectomy with pelvic lymphadenectomy for early-stage
      cervical cancer.
AB  - The objective of this study was to evaluate the problems with miction,
      defecation, and sexuality after a radical hysterectomy with or without adjuvant
      radiotherapy for the treatment of cervical cancer stage I-IIA. This study
      included an observational longitudinal study of self-reported bladder,
      defecation, and sexual problems with a baseline score. Ninety-four women were
      included in the study. An age-matched control group consisted of 224 women. The
      patients showed significantly more negative effects on sexual function compared
      with both the controls and their situation before the treatment throughout 24
      months of follow-up. The problems included less lubrication, a narrow and short
      vagina, senseless areas around the labia, dyspareunia, and sexual
      dissatisfaction. Up to 12 months after the treatment, the patients complained
      significantly more of little or no urge to urinate and diarrhea as compared with
      the controls. Adjuvant radiotherapy did not increase the risk of bladder
      dysfunction, colorectal motility disorders, and sexual functions. We conclude
      that a radical hysterectomy for the treatment of early-stage cervical carcinoma
      is associated with adverse effects mainly on sexual functioning.

PMID- 16803496
TI  - Lymphedema and bladder-emptying difficulties after radical hysterectomy for early
      cervical cancer and among population controls.
AB  - The aim of the study was to acquire knowledge that can be used to refine radical
      hysterectomy to improve quality-of-life outcome. Data were collected in 1996-1997
      by means of an anonymous postal questionnaire in a follow-up study of two cohorts
      (patients and population controls). We attempted to enroll all 332 patients with
      stage IB-IIA cervical cancer registered in 1991-1992 at the seven departments of
      gynecological oncology in Sweden and 489 population controls. Ninety three (37%)
      of the 256 women with a history of cervical cancer who answered the questionnaire
      (77%) were treated with surgery alone. Three-hundred fifty population controls
      answered the questionnaire (72%). Women treated with radical hysterectomy, as
      compared with controls, had an 8-fold increase in symptoms indicating lymphedema
      (25% reported distress due to lymphedema), a nearly 9-fold increase in difficult
      emptying of the bladder, and a 22-fold increase in the need to strain to initiate
      bladder evacuation. Ninety percent of the patients were not willing to trade off
      survival for freedom from symptoms. Avoiding to induce long-term lymphedema or
      bladder-emptying difficulties would probably improve quality of life after
      radical hysterectomy (to cure cervical cancer). Few women want to compromise
      survival to avoid long-term symptoms.

PMID- 16803497
TI  - Vaginal dilation associated with pelvic radiotherapy: a UK survey of current
      practice.
AB  - This paper presents results from the first UK national survey of patient
      information and interventions related to vaginal dilation in pelvic radiotherapy
      (RT). The aim was to elicit current practice with regard to the target
      population, content/process of patient education, and the evaluation of
      compliance in relation to this intervention. A 38-item questionnaire was sent to
      all RT departments (n= 65) and a convenience sample of specialist gynecological
      oncology nurses (n= 166), with response rates of 62% (n= 40) and 31% (n= 52),
      respectively. Data analysis (via SPSS v11) used both descriptive and inferential
      statistics. Divergence of opinion was evident regarding the specific target
      audience for dilator education, and only a limited number of elements of vaginal
      dilator technique achieved consensus. Sixty-seven percent of respondents stated
      they carried out a wider sexual health assessment associated with the provision
      of dilator information, although its content varied considerably. Results suggest
      the provision of vaginal dilation advice may benefit from being placed in the
      wider context of assessing treatment impact on women's sexual health, raising the
      profile of appropriate psychosexual assessment, and intervention in clinical
      oncology practice. Further research could determine the efficacy of vaginal
      dilation in preventing development of vaginal stenosis among women receiving
      pelvic RT.

PMID- 16803498
TI  - Surgery alone or surgery with a combination radiation or chemoradiation for
      management of patients with bulky-stage IB2 cervical carcinoma.
AB  - The management of stage IB2 cervical carcinoma remains controversial. This
      retrospective review evaluates 47 IB2 cervical carcinoma patients treated with
      surgery alone (S), surgery plus postoperative radiotherapy (SR), or surgery plus
      postoperative chemoradiation (SRC). Median progression-free interval (PFI) was
      70.3 months for the SR group (n= 21), 73.3 months for the SRC group (n= 15), and
      33.5 months for the S group (n= 11). The survival rate was 76% for the SR group,
      87% for the SRC group, and 55% for the S group. Overall 5-year survival rate for
      the three groups was 75%. Median follow-up for the patient population was 61.3
      months. The number of the patient and the nonrandomized nature of this study
      preclude any definitive conclusions, but interestingly, the SRC and SR groups
      exhibited a substantially better PFI and overall survival compared to the S
      group. Selection bias does not appear to be a factor since patients in SR or SRC
      group were at greater risk for recurrence (eg, higher incidence of deep stromal
      invasion, parametrial involvement) than patients in the S group; yet, they still
      experienced superior PFI and overall survival. Further studies comparing
      postoperative irradiation and chemoradiation with these patients in a randomized
      phase 3 trial may be warranted.

PMID- 16803499
TI  - Chemotherapy with mitomycin c, ifosfamide, and cisplatin for recurrent or
      persistent cervical cancer.
AB  - The efficacy and toxicity of mitomycin C (MMC), ifosfamide, and cisplatin in
      cervical cancer were evaluated. Between January 1997 and August 2003, 46 patients
      with locally recurrent, persistent, or disseminated cervical cancer were treated
      with MMC 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2) (MIC regimen)
      repeated every 3 weeks (maximum six cycles). In eight patients (17%), the tumor
      involved the pelvis alone, in 11 (24%) the pelvis and extrapelvic sites, and 27
      (59%) had only distant lesions. A total of 213 MIC cycles were administered
      (median six cycles per patient). Of the 44 evaluable patients, the overall
      response rate was 34% (9% complete and 25% partial responses). Median progression
      free interval was 6 months (95% confidence interval [CI], 4-7 months), and
      overall survival was 10 months (95% CI, 6-14 months). Objective response was
      obtained in two patients (11%) with pelvic relapse within previously irradiated
      area and in 13 (50%) of those with extrapelvic lesions (P= 0.01). Leukopenia was
      seen in 59% of patients (grade 3 in 9%). Nonhematologic side effects were mild
      and relatively infrequent. In conclusion, MIC regimen provides satisfactory
      efficacy with acceptable toxicity in advanced cervical cancer patients. Better
      response is seen in lesions outside of the previously irradiated area.

PMID- 16803500
TI  - Salvage chemotherapy with a combination of paclitaxel, ifosfamide, and cisplatin
      for the patients with recurrent carcinoma of the uterine cervix.
AB  - The aim of this study was to assess the efficacy and toxicities of a combination
      of paclitaxel, ifosfamide, and cisplatin (TIP) for recurrent carcinoma of the
      uterine cervix. Fifty-three patients with recurrent cervical carcinoma were
      treated with ifosfamide 1500 mg/m(2) intravenously over 3 h on days 1-3,
      paclitaxel 135 mg/m(2) as a 3-h intravenous infusion, and cisplatin 50 mg/m(2)
      intravenously over 30 min on day 1. The chemotherapy was repeated every 3 weeks
      until there was disease progression or unacceptable toxicity. Forty-five patients
      received at least three courses of treatment and were evaluable for their
      response. Twenty-one patients (46.7%) showed objective responses, including 4.4%
      complete responses and 42.2% partial responses. The median time to progression
      and the overall survival for all the patients were 8.0 months (95% confidence
      interval [CI], 7.1-8.9 months) and 19.0 months (95% CI, 11.9-26.1 months),
      respectively. The median duration of response was 9.0 months. Patients who had
      previously been treated with another chemotherapy after tumor recurrence showed a
      moderate response rate (29.4%) but a shorter time to progression (6 vs 8 months,
      P= 0.0421) and a shorter survival (11 vs 39 months, P= 0.0018). Patients with
      good performance status showed a higher response rate (63.6% vs 30.4%, P= 0.026)
      and a longer time to progression (9 vs 7 months, P= 0.0049). Patients with
      recurrent disease only outside the previous radiotherapy (RT) field exhibited a
      slightly higher response without statistical significance (60.0% vs 36.0%, P=
      0.109). Grade 3 or 4 toxicities included neutropenia in 13% of patients and
      neurotoxicity in 5%. Three deaths during treatment were observed, but two of them
      were due to disease progression. We conclude that the combination chemotherapy
      with TIP yields a high response rate with acceptable toxicity for patients with
      recurrent cervical carcinoma, including those patients who have failed to respond
      to prior platinum-based chemotherapy.

PMID- 16803501
TI  - Phase II study of tirapazamine plus cisplatin in patients with advanced or
      recurrent cervical cancer.
AB  - The aim of this study was to evaluate the activity and toxicity of a tirapazamine
      (TPZ)/cisplatin drug combination in patients with stage IV or recurrent cervical
      cancer. The chemotherapy was administered for a maximum of eight cycles every 21
      days. TPZ was administered intravenously at 330 mg/m(2) over a 2-h infusion,
      followed 1 h later by cisplatin intravenously at 75 mg/m(2) over 1 h on day 1.
      All patients received antiemetics including dexamethasone, ondansetron, and
      lorazepam. Subsequent doses were unchanged, reduced, or omitted according to
      observed toxicity and protocol guidelines. Response evaluation was performed
      every two cycles. Thirty-six patients with stage IV or recurrent cervical cancer
      were treated. Ninety-four percent of patients had prior radiotherapy. Two
      patients had prior chemotherapy. There were two complete responses and eight
      partial responses (27.8%). An additional 11 patients (30.6%) had stable disease
      as their best response. Response rate was greater in tumors outside of the
      previously radiated field (44.4% vs 11.1%). The median time to progression was
      32.7 weeks. The most frequent grade 3 or 4 adverse events were nausea, vomiting,
      and fatigue, which occurred in 30.6%, 25%, and 22% of subjects, respectively.
      Anemia was the most frequent grade 3 or 4 hematologic toxicity at 8.3%. We
      conclude that the combination of cisplatin and TPZ was reasonably well tolerated
      in patients with recurrent or advanced cervical cancer. Further evaluation of
      this drug combination may be warranted.

PMID- 16803502
TI  - Pemetrexed (Alimta, LY231514) demonstrates clinical activity in chemonaive
      patients with cervical cancer in a phase II single-agent trial.
AB  - The objective of this study was to determine the response rate in chemonaive
      patients with inoperable, locally advanced, recurrent, or metastatic cervical
      cancer treated with pemetrexed (Alimta, LY231514), a multitargeted antifolate.
      The patients were treated with either 500 mg/m(2) (11 patients) or 600 mg/m(2)
      (24 patients) of pemetrexed, administered as a 10-min infusion on day 1 of a 21
      day cycle. Patients receiving 500 mg/m(2) dose also received 5 mg/day oral folic
      acid supplementation beginning 2 days prior and ending on day 3 of each cycle. Of
      the 34 patients evaluable for efficacy, six patients (18%) had partial response,
      with median response duration of 3.8 months (range, 3.3-6.6 months). Twenty-four
      patients (71%) had stable disease, one patient (3%) had progressive disease, and
      three patients could not be assessed. Median overall survival was 15.2 months
      (range, 2.9-35.3+ months). Grade 4 hematologic toxicities consisted of
      neutropenia (37%), leukopenia (9%), anemia (6%), and thrombocytopenia (3%). One
      patient died of hypotensive shock associated with frank rectal hemorrhage that
      was considered to be related to the study drug. We conclude that pemetrexed
      therapy showed moderate activity, similar to other active agents, in the
      treatment of locally advanced or metastatic cervical cancer.

PMID- 16803503
TI  - Accuracy of magnetic resonance imaging of inguinofemoral lymph nodes in vulval
      cancer.
AB  - Inguinofemoral lymphadenectomy contributes to the high morbidity related to
      surgical treatment of vulval cancer. The objective of this study was to assess
      the accuracy of magnetic resonance imaging (MRI) in predicting inguinofemoral
      lymph nodes metastasis in women with vulval cancer. We reviewed the clinical,
      MRI, surgical, and pathologic findings of 59 women with vulval cancer who were
      treated at our institution from January 2000 to June 2004. Histology was
      available for 39 women who had undergone inguinofemoral lymphadenectomy. Clinical
      and MRI findings were compared with histology result to assess test accuracy. MRI
      had a positive likelihood ratio (LR+) of 4.8 (95% confidence interval of 2.7-8.6)
      and negative likelihood ratio (LR-) of 0.17 (0.06-0.49). It had a sensitivity of
      85.7% (63.7-97), specificity of 82.1% (69.6-91.1), positive predictive value
      (PPV) of 64.3% (44.1-81.4), and negative predictive value (NPV) of 93.9% (83.1
      98.7). Clinical examination had an LR+ of 6.1 (1.8-21.6) and LR- of 0.69 (0.5
      0.96). It had a sensitivity of 35% (15.3-59.4), specificity of 94.3% (84.3-98.8),
      PPV of 70% (34.7-93.3), and NPV of 79.4% (67.3-88.5). Kappa statistics for
      interobserver and intraobserver agreement were 0.9091 and 0.8475, respectively.
      MRI assessment was accurate in predicting negative nodal status that is
      clinically useful in identifying women who can be spared inguinofemoral
      lymphadenectomy. It is noninvasive and is superior to clinical assessment. In
      clinical practice, this should encourage toward nodal sparing surgery, thus
      lowering surgical-related patient morbidity.

PMID- 16803504
TI  - Lymph node metastasis and lymph vascular space invasion in microinvasive squamous
      cell carcinoma of the uterine cervix.
AB  - The objective of this study was to determine whether the depth of invasion was
      related to lymph vascular space invasion (LVSI) and lymph node metastasis and
      whether there was a correlation between LVSI and lymph node metastasis in stage
      IA cervical cancer. The medical records, including surgical notes and pathologic
      reports, of 202 patients with microinvasive squamous cell carcinoma of the
      uterine cervix were reviewed retrospectively. There was a positive correlation
      between the depth of invasion and the LVSI, and the incidence of lymph node
      metastasis was slightly higher than those reported hitherto for stage IA1
      cervical cancer, especially in the depth of invasion of 1-3 mm group. However,
      among four patients with lymph node metastasis, only two patients had positive
      LVSI. There was no definite correlation between LVSI and lymph node metastasis.
      LVSI could not identify the patients with high risk for lymph node metastasis.

PMID- 16803505
TI  - Assessment of pelvic lymph node micrometastatic disease in stages IB and IIA of
      carcinoma of the uterine cervix.
AB  - The objective of this study was to assess the frequency of micrometastatic
      disease (MID) in pelvic lymph nodes (PLNs) in carcinoma of the uterine cervix
      (CUC) and to determine the risk of recurrence. The PLNs from 289 patients with
      CUC (IB and IIA) were studied. Each PLN was assessed via immunohistochemistry
      using a single histologic section (AE1/AE3). Metastatic deposits were measured
      and the disease status was classified into three groups: 1) absence of metastatic
      disease (MOD); 2) MID, one or more metastatic PLN with only isolated tumor cells
      and/or micrometastases (up to 2 mm); and 3) macrometastatic disease (MAD),
      presence of one or more metastatic PLN with macrometastases (more than 2 mm).
      Eleven patients (3.8%) were classified as having MID and 37 (12.8%) as having
      MAD. The 5-year disease-free survival (DFS) rates for MOD, MAD, and MID were
      88.7%, 80.4%, and 50.0%, respectively (P < 0.001). The Cox proportional hazards
      model showed that MID was an independent variable for recurrence when adjusted
      for MAD, depth of tumor invasion, severity of inflammatory reaction, and use of
      adjuvant radiotherapy. We conclude that the frequency of MID in PLN was low.
      However, patients with MID presented a high risk of recurrence and reduced DFS.

PMID- 16803506
TI  - Benign vascular tumors of female genital tract.
AB  - Vascular tumors are rare in female genital tract (FGT). The aim of this study was
      to analyze the distribution of vascular tumors in FGT and to highlight their
      clinicopathologic features. As a retrospective study, clinical features including
      imaging studies, gross findings, and microscopic features of cases (ten)
      diagnosed as having vascular tumors of FGT over 4 years were reviewed. The age
      range of our cases was 12-52 years. The presenting complaint was abdominal
      pain/mass, postcoital bleeding, and vaginal and vulval mass. In most cases,
      duration of symptoms was 6 months to 2 years. Only one case had a long-standing
      history of 8 years. The vascular tumors occurred most commonly in ovary (six),
      followed by vulva (two), and one each in cervix and vagina. Clinical diagnoses
      ranged from cystadenoma in ovarian tumors to endocervical polyp in cervical
      tumor. Histologically, all were benign vascular neoplasms, ranging from
      hemangioma (five), lymphangioma (one), lymphangioma circumscriptum (one) to
      angiomatosis (two) and arteriovenous malformation (one). Thus, we conclude that
      vascular lesions in FGT can present with symptoms similar to epithelial
      malignancies and may lead to unwarranted radical surgery. Vascular lesions of
      cervix and vulvovaginal region pose special problem during pregnancy. Risk of
      Kasabach-Merritt coagulopathy has to be considered in larger vascular tumors.
      Most of these cases can be treated by surgery.

PMID- 16803507
TI  - Clinical and histopathologic factors related to prognosis in primary squamous
      cell carcinoma of the vagina.
AB  - The goal of this retrospective study concerning primary carcinoma of the vagina
      (PCV) was to analyze clinical and histopathologic prognostic factors in one of
      the largest known material, which comprised 314 patients. PCV is a rare disease,
      and the majority of published studies are based on small materials; therefore,
      the established knowledge concerning prognostic factors is insufficient. Routine
      treatment is based on irradiation with risk for undertreatment or overtreatment,
      which leads to unnecessary complications in the absence of prognostic factors.
      The overall 5-year disease-specific survival rate in this study was 45% and in
      stage I 75%. In the univariate statistical analysis, several factors correlated
      significantly with disease-specific survival. However, in the multivariate
      analysis, there were only three factors that independently could predict poor
      survival-high age at diagnosis, large tumors (> or =4 cm), and advanced stage.
      Common background factors with no prognostic significance were prior
      hysterectomy, other gynecological malignancies, and pelvic irradiation. In
      conclusion, this study has elucidated three strong prognostic factors that might
      be considered in the choice of therapy and also for modification of the FIGO
      guidelines. Increased knowledge concerning complementary biologic markers to
      discriminate between low- and high malignant tumors is however of great
      importance.

PMID- 16803508
TI  - Paget's disease of the vulva: clinicopathologic study of type 1 cases treated at
      a single institution.
AB  - The aim of this study was to evaluate clinicopathologic characteristics of
      primary cutaneous Paget's disease of the vulva. Between 1986 and 2005, 22
      patients with primary cutaneous Paget's disease of the vulva (type 1) were
      treated at Tohoku University Hospital. Medical records were reviewed for
      pathologic diagnosis, patient age, associated neoplasms, type(s) of eczema,
      symptom duration, treatment, surgical procedures, recurrence, and length of
      follow-up. Patient age ranged from 51 to 85 years (median 71.5 years). Median
      duration of symptoms was 24 months (range 2-60 months). Type 1a (intraepithelial)
      Paget's disease accounted for 18 patients, with 3 type 1b (invasive) cases and 1
      type 1c (intraepithelial disease with underlying adenocarcinoma) case. Mean
      length of follow-up was 53.7 months, and median follow-up was 49 months (range 6
      199 months). Only two patients had an associated internal malignancy: T-cell
      leukemia and breast cancer. Mapping biopsy was performed in 14 of the 18 type 1a
      cases. All patients were free of disease at the surgical margins and are alive
      without recurrence. The four patients with type 1b or 1c disease had lymph node
      metastases. Two has died of disease, and two are alive with no recurrence. The
      rate of secondary malignancy seems to be low in primary cutaneous Paget's disease
      of the vulva. Mapping biopsy with careful examination of characteristic skin
      surface may be useful for surgery of type 1a cases. Inguinal lymphadenectomy is
      recommended in cases with question of invasion or known underlying
      adenocarcinoma.

PMID- 16803509
TI  - Plasma proteomic profiling for detecting and differentiating in situ and invasive
      carcinomas of the uterine cervix.
AB  - The objective of this study was to identify multiple plasma protein markers that
      might be characteristic of in situ and invasive cervical cancers. Plasma samples
      obtained from patients with in situ cervical cancer (carcinoma in situ [CIS], n=
      32), from patients with early invasive cervical cancer without lymph node
      metastasis (squamous cell carcinoma [SCC], n= 60), and from age-matched disease
      free controls (n= 37) were analyzed by cation-exchange protein chips and surface
      enhanced laser desorption and ionization time-of-flight mass spectrometry. A
      classification tree defined by six protein peaks could discriminate 84 of the 92
      cancers (CIS and SCC) and 36 of the 37 controls, with 91% sensitivity and 97%
      specificity. In comparing the CIS and SCC samples, two protein peaks with Mr
      values of 6586.41 and 3805.68 were able to classify 55 of the 60 SCC and 31 of
      the 32 CIS samples, with 92% sensitivity and 97% specificity. This study
      demonstrates for the first time the feasibility of differentiating in situ and
      invasive cervical cancers through plasma protein profiling. Identification of the
      proteins different in invasive and in situ cancer may be of great value in the
      understanding of cervical cancer invasion and in the development of novel
      therapeutic intervention.

PMID- 16803510
TI  - Validation of tissue microarray technology using cervical adenocarcinoma and its
      precursors as a model system.
AB  - The tissue microarray (TMA) technology has potentiated large-scale retrospective
      cohort studies using archival formalin-fixed, paraffin-embedded tissues. We used
      a large series of cervical adenocarcinomas to investigate TMA technology in
      assessment of immunohistochemical staining. A TMA was constructed using 273
      archival paraffin blocks from 139 patients with 119 invasive and 20
      adenocarcinoma in situ and 16 normal controls. Two paired cores were obtained
      from specific regions of donor blocks selected at histologic review and were
      arrayed into a recipient blocks. The novel array blocks and some whole donor
      blocks were sectioned and used for immunohistochemical analysis for
      carcinoembryonic antigen, cytokeratin 7, and cytokeratin 20 antibodies as
      potential diagnostic markers. We compared staining in the microarray disks with
      the whole tissue sections. Two paired TM cores were found to yield good
      immunohistochemical staining that was concordant with that of the whole section
      from which it originated in about 97% of cases, and the cores accurately
      represented the morphology of the tumor with respect to tumor typing and
      differentiation in all cases. Our results suggest that TMAs can be successfully
      used for immunohistochemical studies of cervical adenocarcinomas. The areas
      sampled from donor blocks must be selected by careful review of sections from the
      original blocks.

PMID- 16803511
TI  - Promoter methylation of p16, DAPK, CDH1, and TIMP-3 genes in cervical cancer:
      correlation with clinicopathologic characteristics.
AB  - This study was conducted to investigate the promoter methylation status of the
      p16, DAPK, CDH1, and TIMP-3 genes in primary cervical cancer and its correlation
      with clinicopathologic characteristics. Promoter methylation was evaluated using
      a methylation-specific polymerase chain reaction in 78 cervical cancer tissue
      specimens and 24 control, normal cervical tissue specimens. Clinicopathologic
      parameters were obtained from medical records, and the relationship between the
      discrete variables and the methylation status was evaluated. The frequencies of
      promoter methylation of p16, DAPK, CDH1, and TIMP-3 in cervical cancer were 57%,
      44.9%, 52.6%, and 9%, respectively. Primary cervical cancer had significantly
      higher methylation frequencies for the p16 and DAPK promoters than did the
      control, normal cervix (P < 0.0001). The promoter methylation of TIMP-3 was
      significantly higher in adenocarcinoma than in squamous cell carcinoma (41.7% vs
      3%, respectively, P= 0.0175). High-stage cancers exhibited an increased promoter
      methylation frequency for p16 (P= 0.0061). The promoter methylation of the p16
      gene is a frequent event in cervical carcinogenesis and may have potential
      clinical application as a marker for the progression and prognosis of cancer.

PMID- 16803513
TI  - X chromosomal and autosomal loss of heterozygosity and microsatellite instability
      in human cervical carcinoma.
AB  - The study analyzes tumor material and normal tissue from 27 patients with pure
      squamous cell carcinoma of the uterine cervix for loss of heterozygosity (LOH)
      and microsatellite instability (MSI) on 14 autosomal and 11 X chromosomal loci.
      Overall, 4-40% of the informative cases showed LOH at autosomal regions with the
      highest frequency at 3p (21-40%) and a marked frequency at 2q35-q37.1 (12.5%) and
      17p13.3 (10%), representing regions with putative tumor suppressor gene (TSG)
      function. The frequency of X chromosomal LOH ranged from 4% to 20%, with a
      maximum at Xq28 (20%) and Xq11.2-q12 (17%), again indicating alterations in TSG.
      A 12% LOH was seen at Xq21.33-q22.3, a region encoding a protein with a
      regulatory function in the cell cycle via cyclin-dependent kinases. MSI was
      detected in autosomal regions in up to 7% in regions linked to the X chromosome
      in up to 11%, probably indicating alterations of mismatch repair mechanisms. Our
      results and those obtained from the literature suggest that autosomal LOH and MSI
      in carcinomas of the cervix uteri are predominantly found at regions with
      putative TSG function. Beside TSG alterations, X chromosomal LOH is probably more
      strongly connected to disturbances in cell cycle regulation.

PMID- 16803512
TI  - Suppression of human cervical cancer cell lines Hela and DoTc2 4510 by a mixture
      of lysine, proline, ascorbic acid, and green tea extract.
AB  - Cervical cancer, the second most common cancer in women, once metastasized, leads
      to poor prognosis. We investigated the antitumor effect of a nutrient mixture
      (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract
      on human cervical cancer cells Hela (CCL-2) and DoTc2 4510 by measuring cell
      proliferation (MTT assay), modulation of matrix metalloproteinases (MMP)-2 and
      MMP-9) expression (gelatinase zymography), and cancer cell invasive potential
      (Matrigel). NM showed significant antiproliferative effect on CCL-2 and DoTc2
      4510 cancer cells. The NM inhibited CCL-2 expression of MMP-2 and MMP-9 in a dose
      dependent fashion, with virtual total inhibition of MMP-2 at 1000 microg/mL and
      MMP-9 at 500 microg/mL NM. Untreated DoTc2 4510 cells showed MMP-9 expression,
      which was enhanced with phorbol 12-myristate 13-acetate treatment. NM inhibited
      MMP-9 expression in a dose-dependent fashion, with virtual inhibition at 500
      microg/mL. Invasion of human cervical cancer cells CCL-2 and DoTc2 4510 through
      Matrigel decreased in a dose-dependent fashion, with 100% inhibition at 500
      microg/mL NM (P < 0.0001) and 1000 microg/mL NM (P < 0.0001), respectively. Our
      results suggest that the mixture of lysine, proline, arginine, ascorbic acid, and
      green tea extract has potential in the treatment of cervical cancer by inhibiting
      critical steps in cancer development and spread.

PMID- 16803514
TI  - Evaluation of PTEN expression in cervical adenocarcinoma by tissue microarray.
AB  - PTEN, a tumor suppressor gene, appears to negatively control the phosphoinositide
      3-kinase signaling pathway for regulation of cell proliferation and cell
      survival. Somatic PTEN mutations are involved in a variety of tumors, including
      endometrial carcinomas, where PTEN expression is diminished. We examined
      expression of PTEN in a series of cervical adenocarcinomas and precursors, using
      tissue microarray (TMA) technology. TMA blocks were constructed using paraffin
      embedded, formalin-fixed tissues from 273 samples derived from 16 normal cervical
      biopsies, 119 cases of invasive adenocarcinoma, and 20 high-grade cervical
      glandular intraepithelial neoplasia (CGIN). Fresh 3-mum sections were cut and
      immunostained with PTEN, and expression was correlated with clinicopathologic
      variables, including histologic subtypes of adenocarcinoma. In 137 patients, PTEN
      expression was positive in 121 (88%). The intensity and distribution of PTEN
      staining in the tumor tissue were more heterogeneous than those observed in the
      normal tissues. There were no significant differences in distribution or
      intensity of PTEN expression between adenocarcinoma in situ and subtypes of
      invasive adenocarcinoma. Our findings show that unlike the case in most
      endometrial carcinomas, PTEN expression is retained during the process of
      carcinogenesis in the glandular cervix. There is, however, evidence of altered
      distribution and intensity of PTEN expression in cervical adenocarcinoma cells.

PMID- 16803515
TI  - Effects of 17beta-estradiol and progesterone on transcription of human
      papillomavirus 16 E6/E7 oncogenes in CaSki and SiHa cell lines.
AB  - Several in vitro studies have addressed the interactions between
      estrogen/progesterone and human papillomavirus (HPV), but the results are
      controversial. We evaluated the effects of estrogen and progesterone and their
      antagonists on messenger RNA expression of HPV16 E6/E7 in HPV16-positive cell
      lines CaSki and SiHa with real-time reverse-transciptase polymerase chain
      reaction method. Colorimetric assay with tetrazolium salt (WST-1) and flow
      cytometry were used for testing proliferation and apoptosis. No statistically
      significant changes were found after hormone treatment in the expression of HPV16
      E6/E7 or hormone receptors in CaSki and SiHa cell lines. Progesterone increased
      cell proliferation in both the cells, while estrogen increased proliferation of
      SiHa cells only. Estrogen seemed to protect the CaSki cells from apoptosis, and
      tamoxifen did not abrogate this effect. Progesterone slightly increased apoptosis
      of CaSki cells, and this effect was neutralized with RU486. In this study,
      estrogen and progesterone did not change either the transcription levels of HPV16
      E6/E7 or estrogen receptor or progesterone receptor levels. Hormone receptor
      antagonists had no effect on transcription. Both hormones might have a permissive
      effect for the growth of cervical cancer, by promoting cell proliferation and
      making the cells vulnerable to mutations. In addition, estrogen acts as an
      antiapoptotic agent allowing growth advance of the cells infected with oncogenic
      HPV.

PMID- 16803517
TI  - Interleukin-6 polymorphisms and the risk of cervical cancer.
AB  - Recent data implicate that cytokine gene polymorphisms are important in
      pathogenesis of various neoplastic and nonneoplastic human diseases, and it was
      recently suggested that polymorphisms in interleukin (IL)-6 might increase the
      risk of gynecological malignancies, including cervical carcinomas. The aim of
      this case-control study is to compare the IL-6 polymorphisms in cervical cancer
      patients and healthy controls and to assess whether any of these polymorphisms
      would increase the risk of developing cervical cancer. The material in this case
      control study consists of 56 patients with cervical carcinoma and 253 population
      based control subjects, all ethnic Brazilian women. Control subjects were cancer
      free women, following a negative cervical cytology and colposcopy. IL-6
      genotyping was performed using a polymerase chain reaction-based restriction
      fragment length polymorphism. Distribution of the GG, GC, and CC genotypes in
      cases and controls was significantly different (P= 0.033). Compared with the GG
      genotype as reference, the adjusted odds ratio for the combined GC and CC
      genotypes in cancer patients was 1.90 (95% confidence interval, 1.1-3.4). These
      data suggest that women carrying at least one C genotype in their IL-6 promoter
      region (-174G-->C) are at higher risk of developing cervical cancer.

PMID- 16803516
TI  - Association between HLA-DQB1 and cervical dysplasia in Vietnamese women.
AB  - Host genetic background seems to play a key role in cervical carcinogenesis as
      only a small subset of women infected with high-risk human papillomaviruses
      (HPVs) develop cervical cancer. The rate of cervical cancer in Vietnamese women
      is notably high. To explore the association of human leukocyte antigen (HLA)-DQB1
      alleles, HPV infection, and cervical dysplasia in this population, cervical
      smears were obtained from 101 women attending the obstetrics and gynecology
      clinic of Da Nang General Hospital in Vietnam. Besides the Papanicolaou test, HPV
      and HLA-DQB1 genotyping were performed using cervical smear DNA. Additionally, a
      subset of 30 blood samples was used as the gold standard for HLA genotyping. HLA
      DQB1 alleles showed no association with HPV infection status. However, a positive
      association with cervical dysplasia was found for HLA-DQB1*0302 (P= 0.0229,
      relative risk (RR) = 4.737) and HLA-DQB1*0601 (P= 0.0370, RR = 4.038), whereas
      HLA-DQB1*0301 (P= 0.0152, RR = 0.221) was found negatively associated. The low
      diversity of HLA-DQB1 alleles, wide spectrum of HPV genotypes, and high
      prevalence of HPV 16 and HPV 18 observed in the study population suggest a
      permissive/susceptible genetic background that deserves further research. Total
      concordance of HLA-DQB1 genotyping results between blood and cervical cells
      confirms the potential value of cervical smears as an effective tool for the
      development of cervical cancer biomarkers.

PMID- 16803518
TI  - Telomerase activity in the vaginal margins of radical hysterectomy in patients
      with carcinoma of the cervix: correlation with histology and human
      papillomavirus.
AB  - This study was undertaken to evaluate the telomerase activity both in the tumor
      and in the vaginal margins of radical hysterectomy in patients with squamous cell
      carcinoma (SCC) of the cervix. Thirty-three patients with SCC of the cervix
      (study group) and 13 patients with uterine myoma (control group) were
      prospectively studied. Tissue samples were taken from the tumor or cervix,
      anterior vaginal margin (AVM), and posterior vaginal margin (PVM). The specimens
      were analyzed by histopathology, by a telomerase PCR-TRAP-ELISA kit, and by
      polymerase chain reaction using human papillomavirus (HPV) DNA. The telomerase
      activity was significantly higher in the tumor than in the benign cervix (P <
      0.001). There was no difference in telomerase activity in the AVM and PVM in
      patients with cervical carcinoma compared to the control group. Telomerase
      activity was associated with the presence of histologic malignancy in the PVM of
      patients submitted to radical hysterectomy (P= 0.03). This association was not
      observed with the presence of HPV in AVM or PVM in the study group. Telomerase
      activity is a marker of histologic malignancy in patients with SCC of the cervix.
      There was no association between the telomerase activity and the presence of HPV
      in vaginal margins of patients submitted to radical hysterectomy.

PMID- 16803519
TI  - A subgroup of HOX Abd-B gene is differentially expressed in cervical cancer.
AB  - The HOX genes are a family of transcription factors that bind to specific
      sequences of DNA in target genes regulating their expression. The role of HOX
      genes in adult cell differentiation is still obscure, but growing evidence
      suggests that they may play an important role in the development of cancer. In
      order to study the role of the HOX Abd-B genes in cervical cancer, we analyzed
      their expression in cervical tissues. Reverse transcription-polymerase chain
      reaction and RNA in situ hybridization were used to detect HOX Abd-B messenger
      RNA expression in nine normal cervical tissues and ten cervical carcinomas. The
      normal tissues were human papillomavirus (HPV) negative, whereas all invasive
      carcinomas included were HPV16 positive. In this study, we show that HOXA9, A10,
      A11, A13, B9, D11, and D13 genes are expressed in both the epithelium of normal
      tissues and neoplastic cells from squamous cervical carcinomas. Interestingly,
      the HOXC10 and D12 genes were not expressed in any cervical tissues; however,
      HOXB13, C9, C11, C12, C13, D9, and D10 genes were expressed only in the tumoral
      tissues but not in the normal cervix. Our findings suggest that the expression of
      HOXB13, D9, D10, and HOXC cluster (HOXC9, C11-C13) genes might be an important
      step involved in cervical cancer.

PMID- 16803520
TI  - Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor
      progression.
AB  - The incidence of uterine cervical cancer has increased slightly in Western
      countries, with an increase in relatively young women. Overexpression of matrix
      metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many
      cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical
      primary tumors with clinical outcome and risk factors of cervical cancer. One
      hundred sixty-one patients with cervical cancer treated in Umea University
      Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were
      included in the study. Paraffin-embedded tissue samples obtained prior to
      treatment were examined immunohistochemically by specific antibodies for MMP-2
      and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2
      and 31% for MMP-9. Nineteen percent of the samples were intensively positive for
      both proteinases and 47% negative or weak for both. Overexpression of MMP-2
      seemed to predict unfavorable survival under Kaplan-Meier analysis and in the
      multivariate analysis. Early sexual activity and low parity seemed to correlate
      to overexpression of MMP-2. MMP-9 was not associated with survival or sexual
      behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and
      MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated
      with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.

PMID- 16803521
TI  - COX-1 and COX-2 expression in stage I and II invasive cervical carcinoma:
      relationship to disease relapse and long-term survival.
AB  - COX-1 and COX-2 are members of the cyclooxygenase (COX) family, which influence
      tumor invasion and apoptosis. The objective of the study was to assess the
      relationship between COX-1 and COX-2 expression in early-stage disease and
      subsequent disease relapse and long-term survival. Women with FIGO stage I and II
      cervical carcinoma, younger than 50 years, treated between 1981 and 1990 were
      included. COX-1 and COX-2 expressions in the tumors were assessed by
      immunohistochemistry. COX-1 and COX-2 were expressed in 61% (17/28) and 57%
      (16/28) of tumors, respectively. COX-1 nonexpressers showed an improved overall
      survival compared to expressers (log-rank test, P= 0.09). There was no
      significant difference in the overall survival in COX-2 nonexpressers compared to
      expressers (P= 0.6). Out of eight women with disease relapse, COX-1 or COX-2
      expression was noted in six of eight tumors, and both were expressed in five of
      eight tumors. Our preliminary data suggest an adverse prognosis with COX-1
      expression in early-stage cervical carcinoma and a trend toward COX-1 expression
      in disease relapse. The association between COX-2 expression and a worse
      prognosis was not proven in this study.

PMID- 16803522
TI  - Expression of thymidine phosphorylase as an effect prediction factor for uterine
      cervical squamous cell carcinoma after radiotherapy: an immunohistochemical
      study.
AB  - Prognoses in cases of uterine cervical squamous cell carcinoma treated with
      radiotherapy were investigated in association with immunohistochemical expression
      of an angiogenic factor, thymidine phosphorylase (TP). Forty-six cases of uterine
      cervical squamous cell carcinoma mainly treated with radiotherapy during 1992
      2001 at our clinic were studied. All were diagnosed as stages IIB to IVA.
      Paraffin-embedded biopsy specimens excised before radiotherapy were stained
      immunohistochemically using anti-TP monoclonal antibody. The extent of staining
      in both tumor and interstitial cells was graded as (-), (+/-), (+), and (2+).
      Specimens with TP expression levels of (2+) and (+) were regarded as positively
      stained and those with TP expression levels of (+/-) and (-) as negatively
      stained. The efficacy of radiotherapy in both groups was analyzed by the Kaplan
      Meier method. With tumor cells, 5-year survival rates for the positive (n= 38)
      and negative (n= 8) staining groups were 73.9% and 42.9%, respectively; the rate
      being significantly higher for the TP-positive group (log rank, P= 0.0096).
      Contrarily, with staining for interstitial cells, the 5-year survival rates for
      the positive (n= 20) and negative (n= 26) staining groups were 74.1% and 64.6%,
      respectively, with no significant difference (log rank, P= 0.406). The efficacy
      of radiotherapy in the group with positive staining of tumor cells was
      significantly better than in the negative staining group. Immunohistochemical
      expression of TP in tumor cells is suggested as a useful prognostic factor for
      uterine cervical squamous cell carcinomas treated with radiotherapy. Choosing
      therapy for individual cases by referring to factors including TP expression
      should contribute to an improved prognosis.

PMID- 16803523
TI  - Hypoxia and expression of the proapoptotic regulator BNIP3 in cervical cancer.
AB  - Hypoxia plays a major role in the malignant progression of tumors. Here, we
      investigate the expression of Bcl-2/adenovirus E1B 19 kd-interacting protein 3
      (BNIP3), a proapoptotic Bcl-2 family member, and its relationship to hypoxia in
      cervical cancer cell lines and clinical samples of cervical cancer. Cervical
      cancer cell lines were grown under hypoxia or normoxia, and BNIP3 mRNA expression
      was examined by Northern blot analysis. In 50 patients with cervical cancer,
      intratumoral oxygen measurement with the Eppendorf electrode and needle biopsies
      of the tumor were performed. The obtained tissue was subsequently analyzed by
      immunohistochemistry with an anti-BNIP3 antibody. Cervical cancer tissue
      collected upon surgery was used for Northern blot analysis of in vivo BNIP3 mRNA
      expression. BNIP3 mRNA is strongly induced under hypoxic conditions in all
      cervical cancer cell lines investigated. Furthermore, Northern blot analysis
      revealed that BNIP3 mRNA is expressed in cervical cancer tissue. Using
      immunohistochemistry, we demonstrated that BNIP3 protein is expressed in 82% of
      the investigated cervical cancers and that more advanced tumor stages showed
      significantly stronger BNIP3 expression. However, we observed no correlation
      between BNIP3 expression and intratumoral hypoxia. In conclusion, BNIP3 is
      expressed in different cervical cancer cell lines as well as in clinical samples
      of cervical cancer. Although BNIP3 is clearly hypoxia-inducible in vitro, our
      results suggest additional mechanisms of BNIP3 regulation in vivo. Our findings
      therefore highlight a discrepancy between in vitro models of tumor hypoxia and
      the complexity of human cancer.

PMID- 16803524
TI  - Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on
      cervical carcinoma cells.
AB  - 5-Fluorouracil (5-FU) is currently being used as an anticancer drug to reduce
      tumor bulk in order to increase the operability rate and postoperative survival
      in patients with cervical cancer, which has been combined with cisplatin (CP)
      because of its superior activities observed in human carcinoma cells. However,
      the combined anticancer effect of 5-FU and CP in cervical carcinoma cells is
      poorly understood. Therefore, we conducted a study to investigate whether
      anticancer drugs 5-FU and CP may exhibit the combined antiproliferative effect in
      cervical carcinoma cells. Using proteomics analysis, including two-dimensional
      gel electrophoresis and matrix assisted laser desorption/ionization-time of
      flight mass spectrometry (MALDI-TOF-MS), we investigated the antiproliferative
      effect-related proteins after treatment with 5-FU and/or CP. Our experiments
      showed that the combination of 5-FU and CP engaged both the apoptotic pathways:
      the membrane death receptor-mediated apoptosis pathway and the mitochondrial
      apoptotic pathway. Moreover, the combination of 5-FU and CP resulted in
      remarkable increasing susceptibility to apoptosis. We suggest that the
      combination of 5-FU and CP suppresses the growth of cervical carcinoma cells by
      synergistic effect with the induction of apoptosis. In vitro synergistic effect
      of 5-FU and CP supports the basis of the clinical application of the combination
      chemotherapy to the patients with cervical cancer.

PMID- 16803525
TI  - Statistical analysis of pathologic risk factors for intramyometrial lymphvascular
      space involvement in myoinvasive endometrial carcinoma.
AB  - In a retrospective study using univariate analysis, we identified tumor type
      (nonendometrioid vs endometrioid), depth of myoinvasion (MI), mode of MI
      (infiltrative vs cohesive), and direct anatomic invasion of the cervical wall
      from the isthmus as significant positive risk factors for intramyometrial
      lymphvascular space involvement (LVSI). On multivariate analysis, tumor grade,
      depth of MI, and mode of MI retained their significance. We created a grid for
      the relative risks of LVSI with respect to these variables individually or in
      combination. We suggest that our indirect estimate of the risk of LVSI can help
      in assessing prognosis and determining the need for adjuvant therapy whenever
      LVSI is important in clinical decision making, but its pathologic diagnosis is
      uncertain.

PMID- 16803526
TI  - Endometrial cancer patients have a significant risk of harboring isolated tumor
      cells in histologically negative lymph nodes.
AB  - In this study, we examine the prevalence of finding isolated tumor cells (ITCs)
      in negative lymph nodes of endometrial cancer patients using
      immunohistochemistry. Seventy-six endometrial cancer patients with lymph nodes
      histologically negative for metastatic disease were examined. Nodal tissue
      sections were stained with anticytokeratin antibodies AE-1 and CAM 5.2. Nodes
      with single or groups of cells (two to four cells) < or =0.2 mm and showing
      cytokeratin reactivity were positive for ITCs. Findings were compared to features
      of the primary tumor and patient outcome. ITCs were present in 31 of 1712 lymph
      nodes. Fifteen (19.7%) patients had ITC-positive nodes. ITCs involved only pelvic
      nodes in nine cases, only para-aortic nodes in five cases, and pelvic and para
      aortic in one case. Tumor in adnexa was the only pathologic feature associated
      with nodal ITCs (P= 0.0485). All 15 patients with nodal ITCs were alive at follow
      up. One (6.7%) patient suffered recurrent disease but was alive at last
      encounter. Disease recurred in 5 (8.8%) of 57 patients without nodal ITCs. Two
      are alive without disease, two alive with disease, and one died from her cancer.
      In summary, a significant proportion of endometrial cancer patients have ITCs
      detected by immunohistochemistry in histologically negative regional lymph nodes.

PMID- 16803527
TI  - Predictability of retroperitoneal lymph node metastasis by using
      clinicopathologic variables in surgically staged endometrial cancer.
AB  - The purpose of this study was to predict lymphatic involvement in endometrial
      cancer using clinicopathologic variables of patients treated with surgical
      staging. Overall, 461 patients treated with an initial surgical staging procedure
      including complete pelvic-para-aortic lymphadenectomy were included. The mean
      number of resected lymph nodes was 27 (median 26; range 15-83), and 54 patients
      (12%) had lymphatic involvement. Of these patients, 32 had only pelvic, 15 had
      both pelvic and para-aortic, and 7 had isolated para-aortic metastases. In the
      multivariate analysis, deep myometrial invasion (P= 0.02), lymphvascular space
      invasion (P= 0.001), positive peritoneal cytology (P= 0.002), and cervical
      involvement (P= 0.003) predicted retroperitoneal lymph node metastasis (RLN)
      significantly. Two hundred seventy-four patients (59.4%) had at least one of
      these poor prognostic factors identified by multivariate analysis. In this
      patient population, 53 (19.3%) had lymphatic involvement compared to 1 patient in
      the group of 187 patients with low-risk criteria. Ninety-eight percent of
      patients with RLN were predicted by this model, and with the advent of accurate
      diagnostic techniques, 40% of patients could be saved from undergoing
      lymphadenectomy.

PMID- 16803528
TI  - Cholecystectomy and endometrial cancer: a marker of long-term elevated estrogen
      exposure?
AB  - Excess hormones, both endogenous and exogenous, are implicated in the etiology of
      endometrial cancer. We considered whether having had gallstones or a
      cholecystectomy (surgery to remove the gallbladder), which are more common in
      women who are obese and who use exogenous hormones, might be a marker for high
      lifetime levels of estrogen. We conducted a population-based study of endometrial
      cancer cases and community controls in women aged 40-79 years. Participants
      completed an interviewer-administered questionnaire that elicited exposures prior
      to diagnosis or reference date, including history of gallstones and
      cholecystectomy, as well as reproductive history, lifetime body mass, smoking,
      postmenopausal hormone (PMH) use, and other risk factors. Compared to controls,
      cholecystectomy was associated with a 50% increased risk of developing
      endometrial cancer (odds ratio = 1.5 [1.1-2.0]). The relationship appeared to
      depend upon PMH user status; the association was observed only among never
      hormone users. Body mass index did not appear to modify this relationship. Having
      a diagnosis of gallstones was also associated with endometrial cancer, although
      to a lesser magnitude. Although other etiologic factors may play a role in the
      relation between cholecystectomy and endometrial cancer, the current analysis
      suggests that this association is attributable, at least in part, to the sharing
      of hormonal risk factors.

PMID- 16803529
TI  - Loss of p16 in recurrent malignant mixed mullerian tumors of the uterus.
AB  - Uterine malignant mixed mullerian tumors (MMMTs) are rare and highly aggressive
      malignancies with poor clinical prognoses. We examined for differences in the
      oncoprotein profiles of primary versus recurrent MMMTs. Five cases of recurrent
      uterine MMMT were examined by paraffin immunohistochemistry for the expression of
      p53, p16, P-cadherin, and Cerb-B2. P16, p53, and P-cadherin were each expressed
      in 100%, 80%, and 60% of the primary cases, respectively. Three cases expressed
      all three oncoproteins. All five cases were negative for Cerb-B2. No difference
      in antigen expression was seen in the epithelial versus sarcomatous components.
      Primary and recurrent tumors were concordant for p53, P-cadherin, and Cerb-B2.
      However, three cases of recurrent tumors were negative for p16 expression. P53,
      p16, and P-cadherin are common tumor suppressor genes expressed in uterine MMMT.
      Interestingly, p16 protein expression was lost in some cases of MMMTs when they
      recurred. This suggests that the oncoprotein and possibly genetic profile of p16
      changes over time. We did not observe any difference in antigen expression
      between areas of epithelial or sarcomatous differentiation, which would support a
      single pluripotential malignant clone in the histogenesis of these tumors.

PMID- 16803530
TI  - Clinical outcomes of uterine sarcomas: results from 14 years worth of experience
      in the Kinki district in Japan (1990-2003).
AB  - To review clinical outcomes and therapeutic varieties, we were invited to submit
      data from the patients who were treated for uterine sarcomas in Japan from 1990
      to 2003. Uterine sarcomas were defined as leiomyosarcoma (LMS), endometrial
      stromal sarcoma (ESS), and carcinosarcoma (CS). Of a total of 97 patients, 36
      (37.1%) were diagnosed with LMS of the uterine corpus, 15 (15.5%) with ESS, 46
      (47.4%) with CS. Median age at diagnosis was 59 (21-85) years. Clinical stages
      based on FIGO were 41 (42.3%) with stage I disease, 6 (6.2%) with staged II, 34
      (35.1%) with stage III, and 16 (16.5%) with stage IV. The median follow-up period
      for all patients was 13 (1-108) months and median disease-free period was 9 (0
      96) months. The 1-year survival rate and disease-free survival (DFS) rate were
      calculated in patients with all sarcomas (overall survival [OAS], 61.3%; DFS,
      46.6%). Statistical analysis showed that younger age (less than 50 years), early
      stage (stages I and II), and surgical procedure (extended hysterectomy [EH] and
      radical hysterectomy [RH]) were associated with significantly better OAS.
      Histologic types did not affect the survival period. In conclusion, aggressive
      surgery including EH or RH at the time of initial operation offers the
      possibility of prolonged survival.

PMID- 16803531
TI  - Combined adjuvant cisplatin and ifosfamide chemotherapy and radiotherapy for
      malignant mixed mullerian tumors of the uterus.
AB  - The role of adjuvant therapy for malignant mixed mullerian tumors of the uterus
      has not been established. Our aim was to review our experience with sequential
      adjuvant therapy using cisplatin and ifosfamide chemotherapy and radiotherapy
      after surgical staging. A retrospective study of 43 patients from 1995 to 2004
      was undertaken. Survival was calculated using the Kaplan-Meier method and
      compared by the log-rank test. The Cox proportional hazard regression model was
      used to assess the effect of treatment on survival after adjustment for age and
      stage. Twenty-eight patients received adjuvant chemotherapy and 28 patients had
      adjuvant radiotherapy. Twenty-one patients underwent sequential adjuvant
      chemotherapy and radiotherapy. Tumor recurrence occurred in 14 patients at a
      median duration of 10 months. The overall 2- and 5-year survival was 64% and 60%,
      respectively. The 2- and 5-year survival for stage I and II diseases was both
      95%, while the 2-year survival for stage III and IV diseases was 25%. Patients
      who underwent sequential adjuvant therapy had an improved survival compared with
      patients who did not follow the protocol (P= 0.024). Our results with sequential
      adjuvant therapy are encouraging and justify future randomized trials.

PMID- 16803532
TI  - Use of trastuzumab in the treatment of metastatic endometrial cancer.
AB  - Systemic therapy of metastatic endometrial cancer is relatively ineffective.
      Response rates to chemotherapy and hormonal therapy in published studies range
      from 11% to 57%, but most responses are partial and of limited duration. In this
      case, we present a 76-year-old woman with stage IIIA endometrial adenocarcinoma
      who was initially treated with surgery and pelvic radiation. She developed
      multiple pulmonary metastases. She was treated with weekly paclitaxel
      chemotherapy. Immunostaining revealed that the primary endometrial cancer
      overexpressed HER-2/neu. Trastuzumab was added to the regimen, and a dramatic
      partial response was achieved. After a second pulmonary relapse following
      discontinuation of prior therapy, she was again successfully treated with
      trastuzumab in combination with paclitaxel and then docetaxel. Therefore,
      trastuzumab may be a useful adjuvant to taxane-based chemotherapy in some
      patients with metastatic endometrial cancers that overexpress HER-2/neu.

PMID- 16803533
TI  - Serum proteomic features for detection of endometrial cancer.
AB  - To find new potential biomarkers for detection of endometrial cancer (EC), 70
      serum samples including 40 from EC patients and 30 from normal healthy females
      were detected by surface-enhanced laser desorption-ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) using WCX2 (weak cation exchange) protein chip. Mass
      spectra were then assessed with three powerful data-mining tools: a tree
      classifier, Biomarker Wizard software, and Biomarker Patterns System. The
      diagnostic pattern combined with 13 potential biomarkers could differentiate EC
      patients from healthy persons, with a specificity of 100%, sensitivity of 92.5%,
      and total coincidence of 95.7%. The combination of surface-enhanced laser
      desorption-ionization with bioinformatics tools could help find new biomarkers
      and establish with high sensitivity and specificity for the detection of EC.

PMID- 16803534
TI  - Combined E-cadherin, alpha-catenin, and beta-catenin expression is a favorable
      prognostic factor in endometrial carcinoma.
AB  - Cell adhesion molecules, such as epithelial cadherin (E-cadherin), might be
      involved in the processes of tumor invasion and differentiation. The aim of this
      study was to investigate the expression of E-cadherin, alpha-catenin, and beta
      catenin in endometrial carcinoma and to determine the prognostic value of these
      factors. We have investigated the expression of E-cadherin, alpha-catenin, and
      beta-catenin by immunohistochemistry in 225 endometrial carcinomas. The
      correlation between the E-cadherin and the catenins and their correlation with
      several histologic and clinical parameters were analyzed. Negative E-cadherin,
      alpha-catenin, and beta-catenin expression was observed in 44%, 47%, and 33% of
      endometrial carcinomas, respectively, and was correlated with histologic FIGO
      grade 3 (P < 0.001). Negative E-cadherin expression was more often observed in
      nonendometrioid endometrial carcinomas (NEECs) than in endometrioid carcinomas
      (75% versus 43%; P= 0.04). Combined positive E-cadherin, alpha-catenin, and beta
      catenin expression was an independent positive prognostic factor for survival in
      patients with grade 1-2 carcinomas (P= 0.02). Negative E-cadherin expression was
      found to be associated with histologic grade 3 and with NEEC. Combined positive E
      cadherin, alpha-catenin, and beta-catenin expression was a significant prognostic
      factor.

PMID- 16803535
TI  - Microsatellite instability in endometrioid endometrial carcinoma: correlation
      with clinically relevant pathologic variables.
AB  - This study of 218 patients with endometrioid endometrial carcinoma explores the
      relationship between microsatellite instability (MSI) as established by the BAT26
      method and the common pathologic variables of prognostic and therapeutic
      significance. MSI was positively correlated with grade, associated endometrial
      atrophy, squamous metaplasia, isthmic involvement, depth of myoinvasion, vascular
      invasion-associated changes, extrauterine tumor spread, and extramyometrial
      angiolymphatic spread. There was no significant correlation with carcinoma
      developing in adenomyosis, mucinous metaplasia, tumor size, cornual involvement,
      cervical extension, uterine serosal involvement, and targeted lymphoid response.
      The positive correlations are discussed in terms of molecular genetics.

PMID- 16803536
TI  - The detection of microsatellite instability in blind endometrial samples--a
      potential novel screening tool for endometrial cancer in women from hereditary
      nonpolyposis colorectal cancer families?
AB  - Microsatellite instability (MSI) is the phenotypic molecular characteristic of
      the majority of tumors associated with the hereditary nonpolyposis colorectal
      cancer syndrome (HNPCC). Women in this group have an increased risk of
      endometrial cancer (EC). This study aimed to determine whether MSI could be
      demonstrated in blind endometrial samples from women with EC, HNPCC kindreds
      undergoing screening for EC, and women with normal endometrium. Twenty-four women
      with EC, 20 women from HNPCC kindreds, and 20 women undergoing gynecological
      surgery for benign indications underwent blind sampling. MSI analysis was
      performed by conventional polymerase chain reaction using fluorescent-labeled
      primers and automated analysis. Twelve microsatellites were studied with MSI
      defined as evident when novel alleles were seen in endometrial biopsy samples
      compared to genomic DNA. Of the 24 EC samples obtained, sufficient DNA for
      analysis was extracted in 17 cases. Three cases had evidence of MSI in at least
      7/12 loci. None of the endometrium from the two other study groups revealed
      evidence of MSI. This is the first demonstration of MSI in blind endometrial
      biopsies. The ability to demonstrate MSI in heterogeneous endometrial samples
      suggests potential for the development of a novel EC screening tool for women in
      HNPCC kindreds.

PMID- 16803537
TI  - Heparanase expression in both normal endometrium and endometrial cancer.
AB  - The aim of this study was to investigate the relationship between heparanase
      expression and prognostic factors in endometrial cancer, as well as the
      relationship between heparanase expression during phases of the normal
      endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34
      normal endometria in various phases of growth was performed. The heparanase
      expression in the late-proliferative phase of normal endometria was found to be
      significantly higher than in either the early-proliferative or the secretory
      phases (P= .012 and P= .044, respectively). Heparanase expression was also
      significantly higher in endometrial cancer patients with tumors of an advanced
      FIGO stage (P= .0003) and high FIGO grade (P= .004) and with cancers showing
      either deep myometrial invasion (P= .023), lymph node metastasis (P= .006),
      lymphvascular space involvement (P= .048), or positive peritoneal cytology (P=
      .010). The disease-free and overall survival rates of patients with intense
      heparanase expression were significantly lower than those of patients with absent
      or moderate heparanase expression (P= .004 and P= .002, respectively). Heparanase
      may participate in normal endometrial remodeling and can serve as an indicator of
      the aggressive potential and poor prognosis of endometrial cancers.

PMID- 16803538
TI  - CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial
      carcinoma.
AB  - The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental
      carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be
      a susceptibility factor for endometrial hyperplasia (EH) and endometrial
      carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and
      ECa and control subjects using allele-specific polymerase chain reaction-based
      method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a
      fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher
      frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with
      EH, indicating that persons carrying any Val allele are at increased risk for
      developing EH. In the ECa group, patients were also more likely to have CYP1A1
      Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a
      statistically significant increase in relative risk association with any Val
      genotype between patients and controls, suggesting that individuals carrying any
      Val genotype are at increased risk for developing ECa. We concluded that variant
      alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility.
      Further studies with a large sample size should be considered to address issues
      of interactions between CYP1A1 and other risk factors.

PMID- 16803540
TI  - MSH2 splice site mutation and endometrial cancer.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited syndrome of
      cancer susceptibility caused by germ line mutations of genes participating in
      mismatch repair (MMR). Carriers of MMR gene mutations have an increased risk of
      colorectal cancers and cancer of other organs. Tumors of the endometrium
      represent the most frequent extracolonic malignancies in HNPCC. It has been
      suggested that women harboring MMR gene mutations have a higher risk of
      endometrial cancer than of colon cancer. Here, we describe an HNPCC patient with
      early-onset endometrial cancer and a strong familial history of endometrial
      tumors who harbored a germ line MSH2 splice site mutation (IVS9_2A>G). This
      mutation was responsible for abnormal messenger RNA processing, leading to the
      introduction of a premature stop signal and to the expression of a truncated MSH2
      protein. In addition, the same mutation was associated with loss of MSH2 protein
      expression, high microsatellite instability, and PTEN inactivation. Although a
      direct relationship between the endometrial cancer susceptibility and the MSH2
      mutation we found cannot be established, our observations, consistent with the
      work of other authors, suggest the involvement of germ line MSH2 abnormalities in
      endometrial tumor development and support the case for endometrial cancer
      screening in women from HNPCC families.

PMID- 16803539
TI  - Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous
      endometrium.
AB  - We aimed to investigate if expressions of survivin and p27 proteins are involved
      in the development of endometrioid carcinoma, along with whether there are any
      correlations between these proteins and loss of wild-type PTEN that is found in
      up to 80% of endometrial carcinomas. We also studied their correlations with
      classical prognostic factors and survival in endometrial carcinoma. To our
      knowledge, this is the first time survivin expression is investigated in
      endometrial hyperplasia along with endometrioid adenocarcinoma. For
      immunohistochemical analysis, 29 endometrioid adenocarcinoma, 38 endometrial
      hyperplasia, and 10 proliferative endometrium tissue samples were selected in the
      pathology archives. Staining of cells was scored as +2 if >50%, +1 if <50%, and
      negative if none were stained positive. Survivin expression increased from
      proliferative to hyperplasia to carcinoma cases. PTEN and p27 expressions
      decreased in hyperplasia and carcinoma cases with respect to proliferative
      endometrium. All these differences were statistically significant (P < 0.05).
      PTEN positively correlated to p27 (P < 0.05); however, neither was correlated
      with survivin. None of these genes were correlated with classical prognostic
      factors such as grade and myometrial invasion in endometrioid adenocarcinoma.
      However, mean survival was statistically significantly higher in PTEN-positive
      cases (46.6 vs 16.4 months) (P < 0.05). Survivin overexpression might be one of
      the important mechanisms in the development of endometrioid adenocarcinoma along
      with lost or decreased activity of PTEN and p27. However, survivin seems to exert
      its role in ways different from those of PTEN or p27 in the development of
      endometrioid adenocarcinoma. These findings on the role of survivin in
      endometrioid adenocarcinoma should be confirmed and the pathways through which
      survivin acts in endometrioid adenocarcinoma studied further with a larger sample
      size.

PMID- 16803541
TI  - Targeting topoisomerase IIa in endometrial adenocarcinoma: a combined chromogenic
      in situ hybridization and immunohistochemistry study based on tissue microarrays.
AB  - Topoisomerase IIa is a nucleic enzyme that affects the topological structure of
      DNA and also is a target for chemotherapy (ie, anthracyclines). In this study, we
      coevaluated its protein expression with chromosome 17 and gene status. Using
      tissue microarrays, 40 cases of sporadic, primary endometrial adenocarcinomas, 5
      cases of atypical hyperplasia, and 5 cases of benign hyperplasia were obtained
      and reembedded into two paraffin blocks with a core diameter of 1 mm.
      Immunohistochemistry combined with chromogenic in situ hybridization was
      performed in 2 and 5 microm sections, respectively. Finally using a semiautomated
      Image Analysis System, we evaluated the levels of Nuclear labeling index of
      topoisomerase IIa expression. Statistical analysis was performed by SPSS version
      11.0 software. The results indicate that chromosome 17 instability (aneuploidy in
      7/40 cases) and Topo IIa gene deregulation (amplification in 3/40 and deletion in
      1/40 cases) are significant genetic events correlated with biologic behavior in
      endometrial adenocarcinoma. Because protein overexpression was observed in a
      significant proportion of the tumors (18/40), detection of the specific gene
      deregulation mechanism is a crucial process for application of targeted
      chemotherapies, which are characterized by different levels of cardiotoxicity and
      other serious effects.

PMID- 16803542
TI  - Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide,
      vincristine) chemotherapy in gestational trophoblastic neoplasia.
AB  - The aim of this study was to evaluate the efficacy and toxicity of EMA/CO
      (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen
      for the treatment of high-risk gestational trophoblastic neoplasia (GTN). Thirty
      three patients with high-risk GTN, scored according to World Health Organization,
      received 159 EMA/CO treatment cycles between 1994 and 2004. Twenty-three patients
      were treated primarily with EMA/CO, and 10 patients were treated secondarily
      after failure of single agent or MAC (methotrexate, actinomycin D,
      cyclophosphamide, or clorambucile) III chemotherapy. Adjuvant surgery and
      radiotherapy were used in selected patients. Survival, response, and toxicity
      were analyzed retrospectively. The overall survival rate was 90.9% (30/33).
      Survival rates were 91.3% (21/23) for primary treatment and 90% (9/10) for
      secondary treatment. Six (18.2%) of 33 patients had drug resistance. Four of them
      underwent surgery for adjuvant therapy. Three of these patients with drug
      resistance died. Survival and complete response to EMA/CO were influenced by
      liver metastasis, antecedent pregnancy, and histopathologic diagnosis of
      choriocarcinoma. Survival rate was also affected by blood group. The treatment
      was well tolerated. The most severe toxicity was grade 3-4 leukopenia that
      occurred in 24.3% (8/33) of patients and 6.9% (11/159) of treatment cycles.
      Febrile neutropenia occurred in one patient (3%). EMA/CO regimen is highly
      effective for treatment of high-risk GTN. Its toxicity is well tolerated.

PMID- 16803543
TI  - Hepatoid carcinoma of the ovary: immunohistochemical finding of one case and
      literature review.
AB  - Hepatoid carcinoma is a rare ovarian tumor and is thought to be a histopathologic
      subtype different from hepatoid type yolk sac tumor based on its pathologic
      features. A 63-year-old woman who had postmenopausal bleeding and lower abdominal
      pain was found to have right ovarian mass on pelvic examination and computed
      tomography. She had high serum levels of alpha fetoprotein (AFP) and CA125.
      Histologically, the tumor resembled hepatocellular carcinoma by architectural and
      cytologic features. Immunohistochemically tumor cells were immunoreactive for
      AFP, alpha 1 antitrypsin, and carcinoembryonic antigens.

PMID- 16803544
TI  - A case of alpha-fetoprotein-producing adenocarcinoma of the endometrium with a
      hepatoid component as a potential source for alpha-fetoprotein in a
      postmenopausal woman.
AB  - Although case reports of alpha-fetoprotein (AFP)-producing adenocarcinoma other
      than hepatocellular carcinoma have gradually increased in number, AFP-producing
      adenocarcinoma of the endometrium is very rare. The patients universally complain
      of abnormal vaginal bleeding. The patient presented with complaints of epigastric
      discomfort. No vaginal bleeding was observed. Serum AFP concentration was 453
      ng/mL, and lens culinaris agglutinin-reactive AFP percentage of total AFP was
      increased to 67%. Radiologic imaging and endoscopy did not provide evidence of
      any primary carcinoma in the liver and gastrointestinal tract. To investigate the
      unknown origin of high AFP, Pap smear of the endometrium followed by fractional
      curettage was performed and revealed adenocarcinoma of the endometrium. Radical
      hysterectomy with pelvic lymph node dissection and partial omentectomy was
      performed. Histologic study showed a mixture of major AFP-negative endometrioid
      adenocarcinoma and minor medullary proliferation of the AFP-positive hepatoid
      adenocarcinoma cells with eosinophilic cytoplasm and hyaline globules. After the
      surgery followed by four courses of weekly carboplatin and paclitaxel
      administration, serum levels of AFP dropped into normal range. The possible
      existence of AFP-producing adenocarcinoma of the endometrium should be considered
      in a postmenopausal woman even if there is no vaginal bleeding, when AFP
      producing tumor is clinically suspected and the imaging studies fail to confirm
      the diagnosis.

PMID- 16803545
TI  - Endometrial adenocarcinoma following insertion of the levonorgestrel-releasing
      intrauterine system (mirena) in a 36-year-old woman.
AB  - The levonorgestrel-releasing intrauterine system (LNG-IUS), commonly referred to
      as mirena, is an effective form of contraception, which is widely used as an
      intrauterine device. It has a 32-mm long-shaped plastic frame that holds a
      reservoir (on the vertical stem) of 52 mg of levonorgestrel mixed with
      polydimethylsiloxane to allow a steady release of 20 mug of levonorgestrel per
      day within the endometrial cavity through a rate-limiting surface membrane. Apart
      from contraceptive purpose, it is also now commonly used in the management of
      heavy menstrual blood loss. This study included a 36-year old woman who developed
      endometrial cancer following the insertion of the LNG-IUS. Her main presentation
      was irregular vaginal bleeding, which is a common finding in women using this
      form of contraception. Although we would advice caution in investigating such
      women, the LNG-IUS remains a relatively safe method of contraception.

PMID- 16803546
TI  - Intravascular leiomyomatosis and benign metastasizing leiomyoma: an unusual case.
AB  - Benign metastasizing leiomyoma (BML) and intravascular leiomyomatosis (IVL) are
      rare variants of uterine leiomyomas. In our search of available literature, there
      have been only two reports of these conditions occurring in the same patient. We
      report a case of a 42-year-old female presenting with a left L4 nerve root
      lesion, left paravesical lesion, left ovarian cyst, multiple pulmonary
      metastases, and an intracaval lesion. Histology confirmed these to be leiomyomata
      strongly positive for estrogen receptors. Treatment included surgery, in two
      stages, to remove the L4 nerve root, left paravesical lesion, intracaval lesion,
      and a single pulmonary nodule. The remaining tumor was treated with a
      gonadotrophin-releasing hormone agonist, resulting in significant reductions in
      tumor size. It was concluded that the lesions in the lungs were an example of BML
      arising from the initial diagnosis of uterine leiomyoma, and the caval lesion was
      an IVL. Long-term follow-up is recommended, and familiarity with rare forms of
      benign smooth muscle uterine tumors is essential in avoiding misdiagnosis and
      overtreatment.

PMID- 16803547
TI  - Second case of uterine mesonephric adenocarcinoma.
AB  - A second report of an intramural mesonephric adenocarcinoma of the uterus is
      presented. The histogenesis and clinicopathologic outcome of a surgically staged
      malignancy add to the insights and experience of this uncommon disorder.

PMID- 16803548
TI  - Sentinel node mapping in a pregnant woman with cervical cancer: a case report.
AB  - The possibility of reducing morbidity associated with surgical dissection while
      maintaining accurate tumor staging is one of the greatest advantages of the
      sentinel node approach in surgical oncology. The sentinel node mapping has
      already proven to be useful in melanoma, breast cancer, and vulvar cancer. We
      report the first case of sentinel node detection by technetium-labeled
      radiocolloid in a pregnant woman with cervical cancer. The histologic analysis of
      the operative specimen showed a poorly differentiated squamous carcinoma with
      metastasis in the sentinel node and a neoplasic embolus in a blood vessel of the
      placental bed. The lymphatic mapping and sentinel lymph node detection are
      feasible during pregnancy.

PMID- 16803549
TI  - Malignant pericardial effusion with cardiac tamponade in a patient with
      metastatic vaginal adenocarcinoma.
AB  - Malignant pericardial effusion with cardiac tamponade is a rare manifestation of
      metastatic gynecological cancer. A 35-year-old female was diagnosed with clear
      cell adenocarcinoma of the vagina. Four years after partial vaginectomy, she
      developed regional recurrence and was treated with surgical excision followed by
      platinum-based chemotherapy and radiation therapy. Six years later, the patient
      was diagnosed with lung metastases and received a combination adriamycin and
      platinum-based chemotherapy. Shortly after completing treatment, she presented
      with weakness and was found to be hypotensive on physical exam. Computed
      tomography scan confirmed a pericardial effusion with evidence of bilateral heart
      failure. She underwent an emergent pericardiocentesis and eventual pericardial
      window procedure. Metastatic adenocarcinoma of the vagina can present with
      malignant pericardial effusion with cardiac tamponade. Therefore, gynecologists
      and gynecological oncologists need to be familiar with the diagnosis and
      management of this disease process.

PMID- 16803550
TI  - Primary vaginal adenocarcinoma of intestinal type arising from a tubulovillous
      adenoma.
AB  - Enteric or intestinal-type neoplasms of the vagina are extremely rare. The
      present report describes a 55-year-old woman who presented with a 6-week history
      of postmenopausal bleeding. On clinical examination, a lesion on the posterior
      vaginal wall was noticed. Rectovaginal examination suggested a tumor in the
      rectovaginal septum. Biopsy revealed an adenocarcinoma of the intestinal type,
      with a small remnant of a villous adenoma. The histologic interpretation pointed
      in the direction of a metastatic gastrointestinal tumor; yet, clinical
      examination, rectoscopy, colonoscopy, magnetic resonance imaging (MRI) of the
      abdomen, and positron emission tomography (PET) scanning excluded this
      possibility. This led to the conclusion that the lesion was a primary intestinal
      type adenocarcinoma of the vagina that had arisen from a vaginal villous adenoma.
      It is important to be aware of this tumor type and to distinguish them from
      metastatic colorectal adenocarcinoma in order to plan appropriate treatment.

PMID- 16803551
TI  - Malignant eccrine spiradenoma of the vulva: a case report and review of the
      literature.
AB  - Malignant eccrine spiradenoma is a rare skin tumor of sweat gland origin. We
      present the first reported case of this tumor in the female genitalia. Due to the
      rarity of this tumor, there has yet to be an established standard of care. The
      present case is that of a 41-year-old woman with malignant eccrine spiradenoma of
      the periclitoral region. She had an 18-month history of a recurrent, painful mass
      adjacent to the clitoris. Her diagnosis was made after excision of the cystic
      tumor. The patient then underwent a partial radical vulvectomy with bilateral
      sentinel lymph node sampling. As malignant eccrine spiradenoma is a rare tumor,
      no standard care exists for treatment and postoperative management. Based on our
      review of the literature, wide local excision appears to be the preferred initial
      treatment. Furthermore, adjuvant chemotherapy and/or radiation does not seem to
      improve survival in patients with advanced or recurrent cancer. Although lymph
      node sampling and/or lymphadenectomy is frequently reported in the treatment of
      this tumor, hematogenous metastasis can also occur. Therefore, these patients
      require close postoperative follow-up for recurrent disease.

PMID- 16803552
TI  - The problem of accurate initial diagnosis of Bartholin's gland carcinoma
      resulting in delayed treatment and aggressive course of the disease.
AB  - Carcinoma of the Bartholin's gland is a rare lesion accounting for only 5% of all
      vulvar cancers. Initial diagnosis of Bartholin's gland cancer (BGC) and
      recurrence after primary radical surgery and adjuvant radiotherapy poses a
      challenge in the treatment of BGC. This case report presents a particularly
      aggressive course of BGC. Spontaneous rupture of the femoral artery in the
      postoperative period was observed. The length of the survival period from the
      moment of diagnosis amounted to less than 16 months. Aspects of initial diagnosis
      problem and treatment options in groin recurrence of vulvar carcinoma and
      vascular complications are discussed.

PMID- 16803553
TI  - Epithelioid trophoblastic tumor: a case report.
AB  - Epithelioid trophoblastic tumor is a rare and distinctive pathologic entity
      within the complex family of gestational trophoblastic disease. We describe a
      case of epithelioid trophoblastic tumor occurring in a 34-year-old woman, who
      presented with a large uterine tumor 3 years following an uncomplicated
      pregnancy. The clinicopathologic findings in this case are typical of this
      unusual entity and consistent with current literature, with the exception of
      negative beta-human chorionic gonadotrophin levels. The distinguishing features
      from other intermediate trophoblastic tumors and tumor-like lesions are
      discussed.

PMID- 16803555
TI  - Recurrence in a Schuchardt incision after Schauta-Amreich radical vaginal
      hysterectomy for cervical cancer.
AB  - A Schuchardt incision is frequently performed to facilitate access to the
      parametrium during radical vaginal hysterectomy for cervical cancer. We report an
      adenocarcinoma recurrence in a Schuchardt incision 12 months after radical
      vaginal hysterectomy for FIGO stage IB1 cervical cancer. Histology of the primary
      tumor had shown a well-differentiated adenocarcinoma and poorly differentiated
      squamous cell carcinoma of the cervix 2.6 cm in maximum diameter. After further
      surgical therapy and adjuvant radiotherapy, the patient died of disease 51 months
      after the initial operation. Cervical cancers can implant and recur in perineal
      incisions. Thus, it appears prudent to avoid such incisions or, if they are made,
      to irrigate them copiously before closing them.

PMID- 16803554
TI  - Extrauterine choriocarcinoma of the greater omentum after tubal pregnancy: case
      report.
AB  - Extrauterine choriocarcinoma is a rare form of gestational trophoblastic tumor.
      Extrauterine choriocarcinoma of the greater omentum is extremely rare in the
      literature. A 24-year-old female with irregular vaginal bleeding, mimicking as
      ectopic pregnancy, underwent emergency exploratory laparotomy and local excision
      of the greater omentum mass. The serum beta-human chorionic gonadotropin level
      decreased rapidly after operation; however, it rose up again before long.
      Pathology showed choriocarcinoma in the greater omentum. No evidence showed
      lesions on uterus. No other metastasis was found. Multiple courses of combined
      chemotherapy were effective for this case. Surgical excision and combined
      chemotherapy were effective for extrauterine choriocarcinoma of the greater
      omentum.

PMID- 16803557
TI  - Magnetic resonance imaging-assisted FIGO staging system for cervical cancer.

PMID- 16803556
TI  - Management of abnormal uterine hemorrhage with atypical endometrial hyperplasia
      by transcervical resection of endometrium.
AB  - The aim of the study was to assess the feasibility and effect of treating
      atypical endometrial hyperplasia (AEH) with transcervical resection of
      endometrium (TCRE). Five cases of AEH incapable of hysterectomy for various
      reasons were treated with TCRE. All patients were followed up for 3-4 years
      postoperation to evaluate the thickness of endometrium, uterine cavity, and
      prognosis of the disease. All the patients provided informed consent for TCRE. In
      all five cases treated with TCRE, case 1 was for senility, hypertension, diabetes
      mellitus, and obesity; case 4 for senility, obsolete cerebral infarction, and
      hemiplegia; case 5 for uremia and chronic dysfunction of coagulation after renal
      transplantation; cases 2 and 3 for rejection of hysterectomy. All cases were
      followed up for more than 3 years after operation. Four had amenorrhea and one
      had dropping menses. The thickness of endometrium was no more than 5 mm in all
      the cases. TCRE is one available microinvasive surgery alternative to
      hysterectomy for AEH patients contraindicated to hysterectomy.

PMID- 16803560
TI  - Thrombotic thrombocytopenic purpura after stem cell transplantation presenting as
      blurred vision and fundal infiltrates.

PMID- 16803561
TI  - Myocardial infarction following sickle cell chest syndrome.

PMID- 16803562
TI  - The status of new anticoagulants.
AB  - Currently available anticoagulants include heparin, low-molecular weight heparin,
      fondaparinux and warfarin. Despite advances with low-molecular weight heparin and
      fondaparinux, the currently available agents have limitations that have provided
      the impetus for the development of new drugs for prevention and treatment of both
      venous and arterial thromboembolism. Novel anticoagulants targeting specific
      steps in coagulation are in various stages of development. This paper reviews the
      pharmacology of these new agents and describes the results of clinical trials
      with new anticoagulants in more advanced stages of clinical testing.

PMID- 16803563
TI  - A tribute to Sidney Farber-- the father of modern chemotherapy.
AB  - Sidney Farber, world-renowned paediatric pathologist, made major contributions to
      his field but is acknowledged as the father of the modern era of chemotherapy. He
      recognised that folic acid stimulated leukaemic cell growth and enhanced disease
      progression. He hypothesised that folic acid antagonists would inhibit or arrest
      the proliferation of cancer cells. His landmark study, published in 1948,
      demonstrated that a number of folic acid antagonists, including 4-aminopteroyl
      glutamic acid (aminopterin) produced temporary remissions in children with acute
      undifferentiated leukaemia. These observations lead to the development and use of
      other chemotherapeutic agents, either singly or, more effectively, in combination
      for treating childhood and adult malignancies. He introduced actinomycin D for
      the treatment of metastatic and localised Wilms tumour. Under his guidance and
      leadership, both the 'Jimmy Fund', one of the first comprehensive paediatric
      oncology treatment centres, and the Children's Cancer Research Foundation, which
      later became the Dana-Farber Cancer Institute, were founded.

PMID- 16803564
TI  - Comparative genome-wide profiling of post-transplant lymphoproliferative
      disorders and diffuse large B-cell lymphomas.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are a major complication of
      solid organ transplantation, representing a cause of severe morbidity and
      mortality. Apart from Epstein-Barr virus infection, knowledge of the pathogenesis
      of monoclonal PTLD is limited. Powerful analysis techniques, such as whole
      genomic DNA profiling (array comparative genomic hybridisation), can improve our
      understanding of PTLD pathogenesis. Whole genome profiling using the Affymetrix
      GeneChip Human Mapping 10 k 2.0 was performed on 20 PTLD cases and 25 cases of
      diffuse large B-cell lymphoma (DLBCL) from immunocompetent patients as a control
      group. Recurrent lesions were detected among all the samples. Chromosome 18q, 7q,
      3q and 12 were the most common gains in the control group. Chromosomes 5p and 11p
      were commonly gained in PTLD-DLBCL. The latter had frequent losses of 6q, 17p, 1p
      and 9p. Chromosome 12p was the most frequent target of deletions among PTLD-DLBCL
      cases. Loss of heterozygosity (LOH) did not always match DNA loss: chromosome 10
      seemed to be targeted by uniparental disomy in PTLD. Small deletions and gains,
      involving both known (BCL2 and PAX5) and unknown genes (ZDHHC14), were
      identified. These data suggest that PTLD share, at a lower frequency, common
      genetic aberrations with DLBCL from immunocompetent patients. The demonstration
      of 9p13 amplification emphasises the importance of PAX5 in PTLD. The combination
      of DNA copy number and LOH assessment lead to the hypothesis that uniparental
      disomy may be a potential mechanism in B-cell lymphomagenesis.

PMID- 16803565
TI  - In vivo and in vitro cytotoxicity of R-etodolac with dexamethasone in
      glucocorticoid-resistant multiple myeloma cells.
AB  - Glucocorticoids have been widely used in the treatment of multiple myeloma (MM)
      both as single agents and in combination with other drugs. However, primary or
      acquired glucocorticoid resistance occurs in most cases. It was recently reported
      that R-etodolac induced in vitro cytotoxicity in MM cell lines and in primary MM
      cells, as well as synergistically enhanced dexamethasone (Dex)-induced apoptosis
      in Dex-sensitive MM.1S cells. This study examined the in vitro and in vivo
      effects of combination treatment with R-etodolac and Dex on Dex-resistant OPM1
      cells. Treatment with R-etodolac and Dex was found to enhance cytotoxicity,
      inhibit nuclear factor kappaB activity via upregulation of IkappaBalpha, as well
      as enhance Dex-induced caspase activation and poly (ADP)-ribose polymerase
      cleavage in OPM1 cells. R-etodolac also enhanced Dex cytotoxicity in patient MM
      cells that were resistant to glucocorticoids. The in vivo anti-tumour effect of
      this combination on MM cells was evaluated by using severe combined
      immunodeficient mice engrafted with OPM1. Treatment with R-etodolac or Dex alone
      did not induce a significant reduction of tumour volume; in contrast, combination
      treatment with R-etodolac and Dex induced significant synergistic inhibition of
      tumour growth. These data indicate that R-etodolac overcomes resistance to Dex in
      glucocorticoid-resistant MM cells, providing the framework for clinical trials of
      R-etodolac combined with Dex, to improve patient outcome in MM.

PMID- 16803566
TI  - Prospective analysis of treatment outcome and prognostic factors in patients with
      T-cell lymphomas treated by CEOP-B: single institutional study.
AB  - The important prognostic factors were evaluated for T-cell non-Hodgkin lymphoma
      (NHL) patients in a prospective study using the CEOP-B protocol [a modified
      cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen
      that uses epirubicin instead of doxorubicin with the addition of bleomycin].
      Fifty-two patients were enrolled in the study. The overall response rate was
      63.5%. The median progression-free survival (PFS) and median overall survival
      (OS) was 18.0 and 39.5 months respectively. The most common toxicity was
      neutropenia. The factors related to poor outcome were a high International
      Prognostic Index (IPI) and a high 'B' score (bone marrow involvement, B symptoms,
      bulky disease). We developed a new prognostic model, namely the Prognostic Group
      for T cell NHL (PGT) that included four groups: PGT1 (low IPI/low B score), PGT2
      (low IPI/high B score), PGT3 (high IPI/Low B score) and PGT4 (high IPI/Low B
      score). OS and PFS (not reached, 48 months) in the PGT1 group were significantly
      longer than those (11.5 and 4.8 months) in PGT2. The same result was observed in
      the PGT3 and PGT4 groups. The CEOP-B regimen was moderately active and tolerable
      for T-cell NHL patients, and the PGT system might be useful for the prediction of
      long-term survival of T-cell NHL patients.

PMID- 16803567
TI  - Clearance of leukaemic blasts from peripheral blood during standard induction
      treatment predicts the bone marrow response in acute myeloid leukaemia: a pilot
      study.
AB  - Although several parameters are useful for risk stratification of patients with
      acute myeloid leukaemia (AML), there are no firm criteria for predicting response
      to induction treatment of individual patients. Daily flow cytometry (FC)
      analysis, carried out during induction treatment in 30 AML patients, showed that
      the clearance of blasts from peripheral blood (PBC) correlated closely with
      response, as assessed by bone marrow FC on day 14, and by morphologic analysis at
      haematopoietic recovery. Therefore, a major treatment outcome can be predicted
      very early in AML patients, thus providing an opportunity for tailoring treatment
      modalities from the outset.

PMID- 16803568
TI  - Validation of the European Prognostic Index for younger adult patients with acute
      myeloid leukaemia in first relapse.
AB  - In order to validate the European Prognostic Index (EPI) for patients <or=60
      years with acute myeloid leukaemia in first relapse, a cohort of 599 such
      patients, treated between 1980 and 2004 at the MD Anderson Cancer Center, were
      assessed using this prognostic index. Three risk groups were defined: favourable,
      76 patients (13%) [Overall survival (OS), 64% at 1 year, 22% at 5 years];
      intermediate, 137 patients (23%) (OS, 38% at 1 year, 12% at 5 years); and poor,
      386 patients (64%) (OS, 17% at 1 year 6% at 5 years). The EPI is reproducible and
      useful.

PMID- 16803569
TI  - No evidence of significant silencing of Fanconi genes FANCF and FANCB or Nijmegen
      breakage syndrome gene NBS1 by DNA hyper-methylation in sporadic childhood
      leukaemia.
AB  - Fanconi anaemia (FA) and Nijmegen breakage syndrome (NBS) carry a high risk of
      haematological cancer. Affected cellular pathways may be modulated in sporadic
      malignancies and silencing of FANCF through methylation has been shown to cause
      somatic disruption of the FA pathway. Combined bisulphite restriction analysis
      for methylation of FANCF, FANCB and NBS1 was used to investigate 81 sporadic
      acute childhood leukaemias. No methylation was detected at any associated CpG
      sites analysed. This does not exclude very low levels of FANCF, FANCB or NBS1
      methylation, but suggests other factors are responsible for chemo-sensitivity and
      chromosomal instability in sporadic childhood leukaemia.

PMID- 16803570
TI  - Safe adoptive transfer of virus-specific T-cell immunity for the treatment of
      systemic adenovirus infection after allogeneic stem cell transplantation.
AB  - During periods of immunosuppression, such as postallogeneic stem cell
      transplantation (SCT), patients are at significant risk for severe viral
      infections. Human adenovirus (HAdV) infection is a serious complication post-SCT,
      especially in children. Virus-specific T cells are essential for the clearance of
      HAdV, as antiviral chemotherapy has revealed limited success. We present
      feasibility data for a new treatment option using virus-specific donor T cells
      for adoptive transfer of immunity to patients with HAdV-infection/reactivation.
      Virus-specific donor T cells were isolated and infused into nine children with
      systemic HAdV infection after SCT. Isolation was based on gamma-interferon (IFN
      gamma) secretion after short in vitro stimulation with viral antigen, resulting
      in a combination of CD4(+) and CD8(+) T cells. 1.2-50 x 10(3)/kg T cells were
      infused for adoptive transfer. Isolated cells showed high specificity and
      markedly reduced alloreactivity in vitro. Adoptive transfer of HAdV-specific
      immunity was successful in five of six evaluable patients, documented by a dose
      independent and sustained in vivo expansion of HAdV-specific T cells, associated
      with a durable clearance/decrease of viral copies. T-cell infusion was well
      tolerated in all nine patients, except one case with graft-versus-host disease II
      of the skin. In conclusion, induction of a specific T-cell response through
      adoptive transfer was feasible and effective. When performed early in the course
      of infection, adoptive T-cell transfer may protect from HAdV-related
      complications.

PMID- 16803571
TI  - The effect of aprotinin on activated protein C-mediated downregulation of
      endogenous thrombin generation.
AB  - Thrombin plays a central role in coagulation and haemostasis. Binding of thrombin
      to thrombomodulin generates activated protein C (APC), which exerts a negative
      feedback on thrombin formation. Aprotinin, a natural proteinase inhibitor is used
      extensively during cardiac surgery because this procedure is often associated
      with profound activation of coagulation and inflammatory pathways. Some in vitro
      evidences suggest that aprotinin inhibits APC, but the clinical relevance is
      unclear. The recombinant human soluble thrombomodulin (rhsTM)-modified thrombin
      generation (TG) assay was used to investigate the effects of aprotinin on APC in
      plasma samples obtained from healthy volunteers, aprotinin-treated cardiac
      surgical patients and in protein C (PC)-depleted plasma. Based on the results of
      in vitro TG assay, addition of rhsTM (0.75-3.0 microg/ml) to volunteer or patient
      platelet-poor plasma significantly reduced (70.8 +/- 21.9 and 95.3% +/- 4.6%,
      respectively) thrombin formation when compared with PC-depleted plasma (8.3% +/-
      5.2%). Aprotinin (100-200 KIU) caused a small, statistically insignificant
      decrease in the peak thrombin formation in normal and PC-deficient plasma (12.0
      +/- 6.1%). In cardiac surgical patients, levels of functional PC, factor II,
      antithrombin and platelet significantly decreased after cardiopulmonary bypass
      (CPB). Soluble thrombomodulin concentrations were increased after CPB (3.5 +/-
      2.2 to 5.0 +/- 2.2 ng/ml), but they were still within the normal range for human
      plasma. Our results showed that, even though endogenous PC level is decreased
      after CPB, it retains its activity in the presence of thrombomodulin, and
      aprotinin has limited inhibitory effect on APC generation.

PMID- 16803572
TI  - Role of dystrophins and utrophins in platelet adhesion process.
AB  - Platelets are crucial at the site of vascular injury, adhering to the sub
      endothelial matrix through receptors on their surface, leading to cell activation
      and aggregation to form a haemostatic plug. Platelets display focal adhesions as
      well as stress fibres to contract and facilitate expulsion of growth and pro
      coagulant factors contained in the granules and to constrict the clot. The
      interaction of F-actin with different actin-binding proteins determines the
      properties and composition of the focal adhesions. Recently, we demonstrated the
      presence of dystrophin-associated protein complex corresponding to short
      dystrophin isoforms (Dp71d and Dp71) and the uthophin gene family (Up400 and
      Up71), which promote shape change, adhesion, aggregation, and granule
      centralisation. To elucidate participation of both complexes during the platelet
      adhesion process, their potential association with integrin beta-1 fraction and
      the focal adhesion system (alpha-actinin, vinculin and talin) was evaluated by
      immunofluorescence and immunoprecipitation assays. It was shown that the short
      dystrophin-associated protein complex participated in stress fibre assembly and
      in centralisation of cytoplasmic granules, while the utrophin-associated protein
      complex assembled and regulated focal adhesions. The simultaneous presence of
      dystrophin and utrophin complexes indicates complementary structural and
      signalling mechanisms to the actin network, improving the platelet haemostatic
      role.

PMID- 16803573
TI  - The effect of genetic variants in the thrombin activatable fibrinolysis inhibitor
      (TAFI) gene on TAFI-antigen levels, clot lysis time and the risk of venous
      thrombosis.
AB  - Thrombin activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of
      fibrinolysis. High TAFI antigen levels are associated with an increased risk of
      deep venous thrombosis (DVT). Because TAFI levels are partly determined
      genetically, we assessed the association between three TAFI gene polymorphisms (
      438 G/A, 505 A/G and 1040 C/T), TAFI antigen levels and clot lysis times and the
      risk of DVT. Carriers of the 505G allele, which is associated with lower TAFI
      antigen levels than the 505A allele, showed an increased risk of DVT. This
      indicates that the relationship between TAFI and venous thrombosis is more
      complex than previously suggested.

PMID- 16803574
TI  - Clinical relevance of cytogenetic abnormalities at diagnosis of acquired aplastic
      anaemia in adults.
AB  - The outcome of 81 adult aplastic anaemia patients who had successful cytogenetics
      at diagnosis and received immunosuppressive therapy was evaluated. Ten patients
      had an abnormal karyotype, six of which had a trisomy. Four of five evaluable
      patients with a trisomy responded. One patient with monosomy 7 achieved a
      complete response and later developed haemolytic paroxysmal nocturnal
      haemoglobinuria but no recurrence of monosomy 7. None of the patients with a non
      numerical karyotypic abnormality responded. No significant differences in
      survival or later clonal disorders were observed between patients with a normal
      karyotype and those with an abnormal karyotype.

PMID- 16803575
TI  - Effects of human gamma-globin in murine beta-thalassaemia.
AB  - Murine models of beta-thalassaemia have been used to test therapeutic globin gene
      vectors. However, the level of gamma-globin expression necessary to achieve full
      phenotypic correction in these models is unclear. In order to address this issue,
      we carried out breeding and transplantation studies in murine models of beta
      thalassaemia intermedia (Hbb(th-3)/+) and severe beta-thalassaemia major (Hbb(th
      3)/Hbb(th-3)) using transgenic lines expressing various levels of human gamma
      globin. Expression of gamma-globin RNA at a modest 7-14% of total alpha-globin
      RNA resulted in the selective survival of HbF(+) erythrocytes, a fivefold
      increase in total HbF, and a phenotypic improvement in the beta-thalassaemia
      intermedia model. Full normalisation of erythrocyte indices in this model
      required gamma-globin RNA expression at 27% of alpha-globin, resulting in an
      average 40% (6.8 g/dl) HbF. Studies using the homozygous Hbb(th-3) model of
      lethal beta-thalassaemia major demonstrated that even this high level of gamma
      globin expression, for reasons related to the function of the hybrid globin
      tetramers, could only prolong, but not fully support, survival. Taken together,
      these results indicate that only the heterozygous Hbb(th-3) model of beta
      thalassaemia intermedia can be reliably used for the pre-clinical assessment of
      gamma-globin gene therapy vectors, as well as other means of gamma-globin gene
      induction.

PMID- 16803576
TI  - Pulmonary hypertension in patients with sickle cell disease: a longitudinal
      study.
AB  - Although pulmonary hypertension (PHT) is a common complication in patients with
      sickle cell disease (SCD), the rate of development of PHT and the factors that
      affect disease progression are unknown. We observed 93 patients over a median
      follow-up period of 2.6 years (range 0.2-5.1 years). Data were censored at the
      time of death or loss to follow-up. Pulmonary hypertension was associated with an
      increased risk of death (relative risk, 9.24; 95% confidence interval: 1.2-73.3;
      P = 0.01). There was no difference in the risk of death when patients with
      different degrees of PHT were compared. Lactate dehydrogenase and blood urea
      nitrogen were significantly associated with PHT in a logistic regression model.
      Higher levels of fetal haemoglobin and treatment with hydroxycarbamide were
      observed more frequently in patients without PHT. Thirteen per cent of patients
      with no previous evidence of PHT developed PHT following 3 years of observation.
      IN CONCLUSION: (1) PHT, regardless of severity, is associated with an increased
      risk of death in SCD patients; (2) haemolysis is strongly associated with PHT in
      SCD; (3) high levels of fetal haemoglobin and hydroxycarbamide therapy may
      decrease the occurrence of PHT; (4) screening for PHT is indicated for SCD
      patients in their non-crisis, steady states.

PMID- 16803577
TI  - Serum levels of angiogenic factors indicate a pro-angiogenic state in adults with
      sickle cell disease.
AB  - Hypoxia-induced angiogenesis may play an important role in the pathophysiology of
      sickle cell disease (SCD). Serum levels of angiopoietin (Ang)-1, Ang-2, vascular
      endothelial growth factor, placenta growth factor (PlGF), soluble tunica intima
      endothelial kinase 2 (sTIE2), erythropoietin (EPO) and endothelial activation
      markers (soluble vascular adhesion molecule-1, soluble intercellular adhesion
      molecule-1) were determined in controls, HbSS (n = 35) and HbSC (n = 23)
      patients. In the asymptomatic phase, serum Ang-2 (P < 0.001), EPO (P < 0.001) and
      sTIE2 (P = 0.03) were elevated in patients. During painful crises, increased Ang
      2 (P < 0.001) and PlGF (P = 0.04) occurred in HbSS and Ang-2 (P = 0.05) in HbSC
      patients. These results indicate a pro-angiogenic state in SCD, mainly because of
      elevated Ang-2 levels.

PMID- 16803580
TI  - Naturally occurring genetic variation in the age-specific immune response of
      Drosophila melanogaster.
AB  - Immunosenescence, the age-related decline in immune response, is a well-known
      consequence of aging. To date, most studies of age-related changes in immune
      response focused on the cellular and physiological bases of this decline; we have
      virtually no understanding of the genetic basis of age-related changes in the
      immune system or if indeed such control exists. We used 25 chromosome
      substitution lines of Drosophila melanogaster derived from a natural population
      to address three questions: (i) How is the function of the innate immune system
      influenced by age? (ii) Is there a genetic basis for phenotypic variation in
      immune response at different ages? (iii) Is there a genetic basis for differences
      in the way that age influences the immune function? Virgin females from each line
      were assayed for immune response using clearance of infection with Escherichia
      coli at 1 and 4 weeks of age. We found significant genetic variation among lines
      in immune response at each age. Unexpectedly, when averaged across all lines, the
      immune response actually improved with age. However, there was significant
      variation in the effect of age on immune response with 11 lines showing
      improvement, nine lines showing no change and five exhibiting a decline with age.
      There was no genetic correlation of immune response across ages suggesting that
      different loci contribute to variation in immune response at each age. The
      genetic component of the variation in immune response increased with age, a
      pattern predicted by the mutation accumulation model of senescence. However, this
      increase in variation resulted in part from the improvement of the immune
      response in some lines with age. Thus the observed changes in genetic variation
      in immune function with age are not entirely explained by the mutation
      accumulation model.

PMID- 16803581
TI  - The stringent response mediator Rsh is required for Brucella melitensis and
      Brucella suis virulence, and for expression of the type IV secretion system virB.
AB  - Physiological adaptation of intracellular bacteria is critical for timely
      interaction with eukaryotic host cells. One mechanism of adaptation, the
      stringent response, is induced by nutrient stress via its effector molecule
      (p)ppGpp, synthesized by the action of RelA/SpoT homologues. The intracellular
      pathogen Brucella spp., causative agent of brucellosis, possesses a gene
      homologous to relA/spoT, named rsh, encoding a (p)ppGpp synthetase as confirmed
      by heterologous complementation of a relA mutant of Sinorhizobium meliloti. The
      Rsh deletion mutants in Brucella suis and Brucella melitensis were characterized
      by altered morphology, and by reduced survival under starvation conditions and in
      cellular and murine models of infection. Most interestingly, we evidenced that
      expression of virB, encoding the type IV secretion system, a major virulence
      factor of Brucella, was Rsh-dependent. All mutant phenotypes, including lack of
      VirB proteins, were complemented with the rsh gene of Brucella. In addition, RelA
      of S. meliloti functionally replaced Brucella Rsh, describing the capacity of a
      gene from a plant symbiont to restore virulence in a mammalian pathogen. We
      therefore concluded that in the intramacrophagic environment encountered by
      Brucella, Rsh might participate in the adaptation of the pathogen to low-nutrient
      environments, and indirectly in the VirB-mediated formation of the final
      replicative niche.

PMID- 16803582
TI  - Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear
      leukocytes.
AB  - Neisseria gonorrhoeae (gonococcus) infection results in recruitment of
      polymorphonuclear leukocytes (PMNs) to the urethral lumen. Recent work from our
      laboratory demonstrated that N. gonorrhoeae resists killing and replicates within
      PMNs. In this study, we examined the effect of gonococci on PMN viability. Using
      both transmission electron microscopy and light microscopy, we observed nuclear
      condensation after 6 h in PMNs that were resting or challenged with opsonized
      zymosan particles (OPZ). In contrast, N. gonorrhoeae delayed nuclear condensation
      in PMNs for 12 h (13% apoptotic PMNs vs. 90% for resting and 94% for OPZ
      stimulated PMNs). Additionally, DNA fragmentation was reduced in PMNs challenged
      with gonococci for 12 h (28% apoptosis vs. 52% for resting and 98% for OPZ
      stimulated PMNs). However, 74% of PMNs challenged with gonococci had condensed
      nuclei and 67% had fragmented DNA after 24 h. Caspase activity (total caspase,
      caspase-3/7, caspase-9) was reduced at 4 h and mitochondrial integrity was
      preserved at 2 h in PMNs challenged with N. gonorrhoeae. Quantitative reverse
      transcription polymerase chain reaction demonstrated that mRNA levels of X-IAP
      and cIAP-2 remained high after challenge with gonococci, but were downregulated
      in OPZ-stimulated PMNs. Collectively, these findings demonstrate that N.
      gonorrhoeae delayed apoptosis in PMNs, perhaps as a strategy to allow
      intracellular replication.

PMID- 16803583
TI  - Activation of the host cell proinflammatory interleukin-8 response by Chlamydia
      trachomatis.
AB  - Diseases associated with Chlamydia are caused by inflammation-associated tissue
      damage following repeated or chronic infection; however, the mechanism by which
      the inflammatory response is induced is unknown. The inflammatory cytokine
      interleukin-8 (IL-8) is produced by C. trachomatis-infected epithelial cells in a
      bacterial growth-dependent manner. We hypothesized that IL-8 is induced through
      activation of host signalling pathways within Chlamydia-infected cells. Bacterial
      protein synthesis occurring after 15 h post infection (hpi) was required for the
      induction of IL-8, thus, increases in IL-8 mRNA are due to chlamydial growth or a
      bacterial product produced at 15 hpi. The induction of IL-8 was not dependent on
      soluble factors in the supernatant of C. trachomatis-infected cells and therefore
      was associated with an internal cellular signal. The AP-1, NFIL6 (C/EBPbeta) and
      NFkappaB transcriptional regulatory sites of the IL-8 promoter and the host
      NFkappaB signalling pathway were necessary for IL-8 induction by C. trachomatis.
      We conclude that a C. trachomatis growth-dependent factor produced at mid
      developmental stage induces IL-8 within the epithelial cell it infects through
      activation of host signalling pathways.

PMID- 16803584
TI  - Systems biology of virus entry in mammalian cells.
AB  - In this article, we define systems biology of virus entry in mammalian cells as
      the discipline that combines several approaches to comprehensively understand the
      collective physical behaviour of virus entry routes, and to understand the
      coordinated operation of the functional modules and molecular machineries that
      lead to this physical behaviour. Clearly, these are extremely ambitious aims, but
      recent developments in different life science disciplines slowly allow us to set
      them as realistic, although very distant, goals. Besides classical approaches to
      obtain high-resolution information of the molecules, particles and machines
      involved, we require approaches that can monitor collective behaviour of many
      molecules, particles and machines simultaneously, in order to reveal design
      principles of the systems as a whole. Here we will discuss approaches that fall
      in the latter category, namely time-lapse imaging and single-particle tracking
      (SPT) combined with computational analysis and modelling, and genome-wide RNA
      interference approaches to reveal the host components required for virus entry.
      These techniques should in the future allow us to assign host genes to the
      systems' functions and characteristics, and allow emergence-driven, in silico
      assembly of networks that include interactions with increasing hierarchy
      (molecules-multiprotein complexes-vesicles and organelles), and kinetics and
      subcellular spatiality, in order to allow realistic simulations of virus entry in
      real time.

PMID- 16803585
TI  - Hosting the severe acute respiratory syndrome coronavirus: specific cell factors
      required for infection.
AB  - As with all viruses, the severe acute respiratory syndrome coronavirus (SARS-CoV)
      utilizes specific host cell factors during its infection cycle. Some of these
      factors have been identified and are now increasingly scrutinized as targets to
      intervene with infection. In this brief review, we describe the current
      understanding of how the SARS-CoV is able to use the cellular machinery for its
      replication.

PMID- 16803586
TI  - Interaction between two murein (peptidoglycan) synthases, PBP3 and PBP1B, in
      Escherichia coli.
AB  - The murein (peptidoglycan) sacculus is an essential polymer embedded in the
      bacterial envelope. The Escherichia coli class B penicillin-binding protein (PBP)
      3 is a murein transpeptidase and essential for cell division. In an affinity
      chromatography experiment, the bifunctional transglycosylase-transpeptidase
      murein synthase PBP1B was retained by PBP3-sepharose when a membrane fraction of
      E. coli was applied. The direct protein-protein interaction between purified PBP3
      and PBP1B was characterized in vitro by surface plasmon resonance. The
      interaction was confirmed in vivo employing two different methods: by a bacterial
      two-hybrid system, and by cross-linking/co-immunoprecipitation. In the bacterial
      two-hybrid system, a truncated PBP3 comprising the N-terminal 56 amino acids
      interacted with PBP1B. Both synthases could be cross-linked in vivo in wild-type
      cells and in cells lacking FtsW or FtsN. PBP1B localized diffusely and in foci at
      the septation site and also at the side wall. Statistical analysis of the
      immunofluorescence signals revealed that the localization of PBP1B at the
      septation site depended on the physical presence of PBP3, but not on the activity
      of PBP3. These studies have demonstrated, for the first time, a direct
      interaction between a class B PBP (PBP3) and a class A PBP (PBP1B) in vitro and
      in vivo, indicating that different murein synthases might act in concert to
      enlarge the murein sacculus during cell division.

PMID- 16803587
TI  - pH-dependent pore-forming activity of OmpATb from Mycobacterium tuberculosis and
      characterization of the channel by peptidic dissection.
AB  - Mycobacteria are characterized by an unusual cell wall that controls nutrient and
      small hydrophilic compound permeability. Porin-like proteins are necessary to
      ensure the transport of molecules into the cell. Here, we investigated the pore
      forming properties of OmpATb, a porin from Mycobacterium tuberculosis, in lipid
      bilayers. Multi-channel experiments showed an asymmetric behaviour with channel
      closures at negative critical voltages (Vc) and a strong decrease in Vc at acidic
      pH. Single-channel experiments gave conductance values of about 850 +/- 80 pS in
      1 M KCl and displayed a weak cationic selectivity in 4-8 pH range. The production
      and characterization of a series of truncated OmpATb proteins, showed that the
      central domain (OmpATb73-220) was sufficient to induce the ion channel properties
      of the native protein in lipid bilayers, i.e. asymmetric insertion, pH-dependent
      voltage closure, cationic selectivity and similar conductance values in 1 M KCl.
      Western blot analysis suggests that the presence of OmpATb is only restricted to
      certain pathogenic species. Therefore, the propensity of channels of native
      OmpATb to close at low pH may represent an intrinsic property allowing pathogenic
      mycobacteria to adapt and survive to mildly acidic conditions, such as those
      encountered within the macrophage phagosome.

PMID- 16803589
TI  - Lethal fragmentation of bacterial chromosomes mediated by DNA gyrase and
      quinolones.
AB  - When DNA gyrase is trapped on bacterial chromosomes by quinolone antibacterials,
      reversible complexes form that contain DNA ends constrained by protein. Two
      subsequent processes lead to rapid cell death. One requires ongoing protein
      synthesis; the other does not. The prototype quinolone, nalidixic acid, kills
      wild-type Escherichia coli only by the first pathway; fluoroquinolones kill by
      both. Both lethal processes correlated with irreversible chromosome
      fragmentation, detected by sedimentation and viscosity of DNA from quinolone
      treated cells. However, only fluoroquinolones fragmented purified nucleoids when
      incubated with gyrase purified from wild-type cells. A GyrA amino acid
      substitution (A67S) expected to perturb a GyrA-GyrA dimer interface allowed
      nalidixic acid to fragment chromosomes and kill cells in the absence of protein
      synthesis; moreover, it made a non-inducible lexA mutant hypersusceptible to
      nalidixic acid, a property restricted to fluoroquinolones with wild-type cells.
      The GyrA variation also facilitated immunoprecipitation of DNA fragments by GyrA
      antiserum following nalidixic acid treatment of cells. The ability of changes in
      both gyrase and quinolone structure to enhance protein synthesis-independent
      lethality and chromosome fragmentation is explained by drug-mediated
      destabilization of gyrase-DNA complexes. Instability of type II topoisomerase-DNA
      complexes may be a general phenomenon that can be exploited to kill cells.

PMID- 16803590
TI  - Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in
      Leishmania mexicana.
AB  - In the past, ultrastructural investigations of Leishmania mexicana amastigotes
      revealed structures that were tentatively identified as autophagosomes. This
      study has now provided definitive data that autophagy occurs in the parasite
      during differentiation both to metacyclic promastigotes and to amastigotes,
      autophagosomes being particularly numerous during metacyclic to amastigote form
      transformation. Moreover, the results demonstrate that inhibiting two major
      lysosomal cysteine peptidases (CPA and CPB) or removing their genes not only
      interferes with the autophagy pathway but also prevents metacyclogenesis and
      transformation to amastigotes, thus adding support to the hypothesis that
      autophagy is required for cell differentiation. The study suggests that L.
      mexicana CPA and CPB perform similar roles to the aspartic peptidase PEP4 and the
      serine peptidase PRB1 in Saccharomyces cerevisiae. The results also provide an
      explanation for why L. mexicana CPA/CPB-deficient mutants transform to
      amastigotes very poorly and lack virulence in macrophages and mice.

PMID- 16803592
TI  - In vivo, fliC expression by Salmonella enterica serovar Typhimurium is
      heterogeneous, regulated by ClpX, and anatomically restricted.
AB  - FliC is a natural antigen recognized by the innate and adaptive immune systems
      during Salmonella infection in mice and humans; however, the regulatory
      mechanisms governing its expression in vivo are incompletely understood. Here, we
      use flow cytometry to quantify fliC gene expression in single bacteria. In vitro,
      fliC transcription was not uniformly positive; a viable fliC-negative
      subpopulation was also identified. Intracellular Salmonella repressed
      transcription of fliC and its positive regulator fliA, but constitutively
      transcribed the master regulator flhD; fliC repression required ClpXP protease,
      known to degrade FlhD. In orally infected mice, fliC transcription was
      anatomically restricted: Salmonella transcribed fliC in the Peyer's Patches (PP)
      but not in the mesenteric lymph nodes and spleen. The intracellularly transcribed
      pagC promoter was upregulated by Salmonella in all tissues, defining the infected
      PP as a unique environment that initiates expression of intracellularly induced
      genes and yet permits transcription of fliC. Because a single bacterium can
      escape the GI tract to colonize deeper tissues, heterogeneous gene expression may
      have important implications for Salmonella pathogenesis: FliC-positive bacteria
      in the PP could stimulate inflammation and facilitate the priming of FliC
      specific immune responses, while FliC-negative bacteria escape host detection in
      the gut and spread to systemic sites of replication.

PMID- 16803591
TI  - Identification of the lipopolysaccharide modifications controlled by the
      Salmonella PmrA/PmrB system mediating resistance to Fe(III) and Al(III).
AB  - Iron is an essential metal but can be toxic in excess. While several homeostatic
      mechanisms prevent oxygen-dependent killing promoted by Fe(II), little is known
      about how cells cope with Fe(III), which kills by oxygen-independent means.
      Several Gram-negative bacterial species harbour a regulatory system - termed
      PmrA/PmrB - that is activated by and required for resistance to Fe(III). We now
      report the identification of the PmrA-regulated determinants mediating resistance
      to Fe(III) and Al(III) in Salmonella enterica serovar Typhimurium. We establish
      that these determinants remodel two regions of the lipopolysaccharide, decreasing
      the negative charge of this major constituent of the outer membrane. Remodelling
      entails the covalent modification of the two phosphates in the lipid A region
      with phosphoethanolamine and 4-aminoarabinose, which has been previously
      implicated in resistance to polymyxin B, as well as dephosphorylation of the
      Hep(II) phosphate in the core region by the PmrG protein. A mutant lacking the
      PmrA-regulated Fe(III) resistance genes bound more Fe(III) than the wild-type
      strain and was defective for survival in soil, suggesting that these PmrA
      regulated lipopolysaccharide modifications aid Salmonella's survival and spread
      in non-host environments.

PMID- 16803593
TI  - Shutdown decay of mRNA.
AB  - Although plasmid-borne and chromosomal toxin-antitoxin (TA) operons have been
      known for some time, the recent identification of mRNA as the target of at least
      two different classes of toxins has led to a dramatic renewal of interest in
      these systems as mediators of stress responses. Members of the MazF/PemK family,
      the so-called mRNA interferases, are ribonucleases that inhibit translation by
      destroying cellular mRNAs under stress conditions, while the founder member of
      the RelE family promotes cleavage of mRNAs through the ribosome. Detailed
      structures of these enzymes, often in complex with their inhibitors, have
      provided vital clues to their mechanisms of action. The primary role and
      regulation of these systems has been the subject of some controversy. One model
      suggests they play a beneficial role by wiping the slate clean and preventing
      wasteful energy consumption by the translational apparatus during adaptation to
      stress conditions, while another favours the idea that their main function is
      programmed cell death. The two models might not be mutually exclusive if a side
      effect of prolonged exposure to toxic RNase activity without de novo synthesis of
      the inhibitor were a state of dormancy for which we do not yet understand the key
      to recovery. In this review, I discuss the recent developments in the rapidly
      expanding field of what I refer to as bacterial shutdown decay.

PMID- 16803594
TI  - PtxR modulates the expression of QS-controlled virulence factors in the
      Pseudomonas aeruginosa strain PAO1.
AB  - The production of several virulence factors by Pseudomonas aeruginosa is
      regulated through the hierarchical cell-density dependent quorum sensing (QS)
      systems las and rhl. A third component of the QS hierarchy, the Pseudomonas
      quinolone signal PQS, also controls the expression of several genes. We
      previously described P. aeruginosa PtxR as a transcriptional activator of the
      exotoxin A gene toxA. Here, we provide evidence that PtxR regulates the
      production of other virulence factors. Mutation of ptxR in PAO1 increased
      pyocyanin production. This increase was reduced in the presence of a ptxR
      plasmid. Throughout the growth cycle, PtxR reduced the expression of the
      pyocyanin operon phzA1-G1 but not phzA2-G2. As pyocyanin production is
      stringently controlled by QS, we examined the effect of PtxR on QS-related genes
      in PAO1. PtxR also reduced the expression of the PQS synthesis operon pqsABCDE.
      ptxR mutation increased the expression of the rhamnolipid synthesis gene rhlA but
      decreased lasB expression. The expression of the RhlI synthase gene rhlI and the
      production of the C(4)-HSL autoinducer were increased in the ptxR mutant, while
      the expression of the LasI synthase gene lasI and the production of 3OC(12)-HSL
      were reduced. These results suggest that PtxR negatively regulates the expression
      of the rhamnolipid and pyocyanin genes through rhlI and the pqsABCDE operon while
      it positively regulates the expression of lasB through lasI.

PMID- 16803595
TI  - An rplKDelta29-PALG-32 mutation leads to reduced expression of the regulatory
      genes ccaR and claR and very low transcription of the ceaS2 gene for clavulanic
      acid biosynthesis in Streptomyces clavuligerus.
AB  - The transcriptional and translational control of the biosynthesis of the beta
      lactamase inhibitor clavulanic acid is a subject of great scientific and
      industrial interest. To study the role of the ribosomal protein L11 on control of
      clavulanic acid gene transcription, the DNA region aspC-tRNA(trp)-secE-rplK-rplA
      rplJ-rplL of Streptomyces clavuligerus was cloned and characterized. An S.
      clavuligerus rplK(DeltaPALG) mutant, with an internal 12 nucleotides in-frame
      deletion in the rplK gene, encoding the L11 (RplK) ribosomal protein lacking
      amino acids (29)PALG(32), was constructed by gene replacement. This deletion
      alters the L11 N-terminal domain that interacts with the RelA and class I
      releasing factors-mediated translational termination. The mutant grew well,
      showed threefold higher resistance to thiostrepton, did not form spores and
      lacked diffusible brown pigments, as compared with the wild-type strain. The wild
      type phenotype was recovered by complementation with the native rplK gene. S.
      clavuligerus rplK(DeltaPALG) produced reduced levels of clavulanic acid (15-26%
      as compared with the wild type) and cephamycin C (40-50%) in cultures grown in
      defined SA and complex TSB media. The decreased yields resulted from an impaired
      transcription of the regulatory genes ccaR and claR and the cefD and ceaS2 genes
      for cephamycin and clavulanic acid biosynthesis respectively. Expression of ceaS2
      encoding carboxyethylarginine synthase (CEAS), the precursor-committing enzyme
      for clavulanic acid biosynthesis, was particularly affected in this mutant. In
      the wild-type strain polyphosphorylated nucleotides peaked at 36-48 h of growth
      in SA cultures whereas expression of the cephamycin and clavulanic acid genes
      occurred 12-24 h earlier than the increase in ppGpp indicating that there is no
      strict correlation between the peak of ppGpp and the onset of transcription of
      the clavulanic acid and cephamycin C biosynthesis. The drastic effect of the
      rplK(DeltaPALG) mutation on the onset of expression of the ceaS2 and the
      regulatory ccaR and claR genes and the lack of correlation with ppGpp levels
      suggest that the onset of transcription of these genes is modulated by the
      conformational alteration of the N-terminal region of L11 probably by interaction
      with the nascent peptide releasing factors and with RelA.

PMID- 16803596
TI  - Neisseria meningitidis NhhA is a multifunctional trimeric autotransporter
      adhesin.
AB  - NhhA, Neisseriahia/hsf homologue, or GNA0992, is an oligomeric outer membrane
      protein of Neisseria meningitidis, recently included in the family of trimeric
      autotransporter adhesins. In this study we present the structural and functional
      characterization of this protein. By expressing in Escherichia coli the full
      length gene, deletion mutants and chimeric proteins of NhhA, we demonstrated that
      the last 72 C-terminal residues are able to allow trimerization and localization
      of the N-terminal protein domain to the bacterial surface. In addition, we
      investigated on the possible role of NhhA in bacterial-host interaction events.
      We assessed in vitro the ability of recombinant purified NhhA to bind human
      epithelial cells as well as laminin and heparan sulphate. Furthermore, we shown
      that E. coli strain expressing NhhA was able to adhere to epithelial cells, and
      observed a reduced adherence in a meningococcal isogenic MC58DeltaNhhA mutant. We
      concluded that this protein is a multifunctional adhesin, able to promote the
      bacterial adhesion to host cells and extracellular matrix components.
      Collectively, our results underline a putative role of NhhA in meningococcal
      pathogenesis and ascertain its structural and functional belonging to the
      emerging group of bacterial autotransporter adhesins with trimeric architecture.

PMID- 16803597
TI  - The Legionella pneumophila IcmS-LvgA protein complex is important for Dot/Icm
      dependent intracellular growth.
AB  - Many bacterial pathogens require a functional type IV secretion system (T4SS) for
      virulence. Legionella pneumophila, the causative agent of Legionnaires' disease,
      employs the Dot/Icm T4SS to inject a large number of protein substrates into its
      host, thereby altering phagosome trafficking. The L. pneumophila T4SS substrate
      SdeA has been shown to require the accessory factor IcmS for its export. IcmS,
      defined as a type IV adaptor, exists as a heterodimer with IcmW and this complex
      functions in a manner similar to a type III secretion chaperone. Here we report
      an interaction between IcmS and the previously identified virulence factor LvgA.
      Similar to the icmS mutant, the lvgA mutant appears to assemble a fully
      functional Dot/Icm complex. Both LvgA and IcmS are small, acidic proteins
      localized to the cytoplasm and are not exported by the Dot/Icm system, suggesting
      they form a novel type IV adaptor complex. Inactivation of lvgA causes a minimal
      defect in growth in the human monocytic cell line U937 and the environmental host
      Acanthamoeba castellanii. However, the lvgA mutant was severely attenuated for
      intracellular growth of L. pneumophila in mouse macrophages, suggesting LvgA may
      be a critical factor that confers host specificity.

PMID- 16803598
TI  - Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and
      genome-wide expression studies.
AB  - Candida glabrata emerged in the last decade as a common cause of mucosal and
      invasive fungal infection, in large part due to its intrinsic or acquired
      resistance to azole antifungals such as fluconazole. In C. glabrata clinical
      isolates, the predominant mechanism behind azole resistance is upregulated
      expression of multidrug transporter genes CDR1 and PDH1. We previously reported
      that azole-resistant mutants (MIC >or= 64 microg ml(-1)) of strain 66032 (MIC =
      16 microg ml(-1)) similarly show coordinate CDR1-PDH1 upregulation, and in one of
      these (F15) a putative gain-of-function mutation was identified in the single
      homologue of Saccharomyces cerevisiae transcription factors Pdr1-Pdr3. Here we
      show that disruption of C. glabrata PDR1 conferred equivalent fluconazole
      hypersensitivity (MIC = 2 microg ml(-1)) to both F15 and 66032 and eliminated
      both constitutive and fluconazole-induced CDR1-PDH1 expression. Reintroduction of
      wild-type or F15 PDR1 fully reversed these effects; together these results
      demonstrate a role for this gene in both acquired and intrinsic azole resistance.
      CDR1 disruption had a partial effect, reducing fluconazole trailing in both
      strains while restoring wild-type susceptibility (MIC = 16 microg ml(-1)) to F15.
      In an azole-resistant clinical isolate, PDR1 disruption reduced azole MICs eight-
      to 64-fold with no effect on sensitivity to other antifungals. To extend this
      analysis, C. glabrata microarrays were generated and used to analyse genome-wide
      expression in F15 relative to its parent. Homologues of 10 S. cerevisiae genes
      previously shown to be Pdr1-Pdr3 targets were upregulated (YOR1, RTA1, RSB1,
      RPN4, YLR346c and YMR102c along with CDR1, PDH1 and PDR1 itself) or downregulated
      (PDR12); roles for these genes include small molecule transport and
      transcriptional regulation. However, expression of 99 additional genes was
      specifically altered in C. glabrata F15; their roles include transport (e.g.
      QDR2, YBT1), lipid metabolism (ATF2, ARE1), cell stress (HSP12, CTA1), DNA repair
      (YIM1, MEC3) and cell wall function (MKC7, MNT3). These azole resistance
      associated changes could affect C. glabrata tissue-specific virulence; in support
      of this, we detected differences in F15 oxidant, alcohol and weak acid
      sensitivities. C. glabrata provides a promising model for studying the genetic
      basis of multidrug resistance and its impact on virulence.

PMID- 16803599
TI  - Review article: recent advances in the management of bleeding gastric varices.
AB  - Gastric variceal bleeding can be challenging to the clinician. Tissue adhesives
      can control acute bleeding in over 80%, with rebleeding rates of 20-30%, and
      should be first-line therapy where available. Endoscopic ultrasound can assist in
      better eradication of varices. The potential risks of damage to equipment and
      embolic phenomena can be minimized with careful attention to technique. Variceal
      band ligation is an alternative to tissue adhesives for the management of acute
      bleeding, but not for secondary prevention due to a higher rate of rebleeding.
      Endoscopic therapy with human thrombin appears promising, with initial
      haemostasis rates typically over 90%. The lack of controlled studies for thrombin
      prevents universal recommendation outside of clinical trials. Balloon occluded
      retrograde transvenous obliteration is a recent technique for patients with
      gastrorenal shunts, although its use is limited to clinical trials. Transjugular
      intrahepatic portosystemic stent shunt is an option for refractory bleeding and
      secondary prophylaxis, with uncontrolled studies demonstrating initial
      haemostasis obtained in over 90%, and rebleeding rates of 15-30%. Non
      cardioselective beta-blockers are an alternative to transjugular intrahepatic
      portosystemic stent shunt for secondary prophylaxis, although the evidence is
      limited. Shunt surgery should be considered in well-compensated patients.
      Splenectomy or embolization is an option in patients with segmental portal
      hypertension.

PMID- 16803600
TI  - Review article: intestinal failure.
AB  - Intestinal failure is a specific disease entity resulting from intestinal
      resection or disease-associated malabsorption and characterized by the inability
      to maintain protein-energy, fluid, electrolyte or micronutrient balance. We
      performed a MEDLINE search (1966-2006) to identify relevant articles, using
      keywords intestinal failure, parenteral or enteral nutrition, intestinal fistula
      and short bowel syndrome. Causes of intestinal failure are varied, with self
      limiting or 'Type 1' intestinal failure occurring relatively commonly following
      abdominal surgery, necessitating short-term fluid or nutritional support. The
      rarer, 'Type 2' intestinal failure, is associated with septic, metabolic and
      complex nutritional complications, usually following surgical resection in
      patients with Crohn's or mesenteric vascular disease. A multidisciplinary
      approach to the management of patients with Type 2 intestinal failure is crucial:
      resolution of sepsis is required before adequate nutritional repletion can be
      achieved, and it is important to optimize nutritional status, not only through
      enteral or parenteral supplementation, but also by addressing complications of
      short bowel syndrome, before considering definitive surgical reconstruction. A
      structured approach to the management of Type 2 intestinal failure should reduce
      the likelihood of these complex patients developing 'Type 3' intestinal failure,
      which is characterized by the need for long-term parenteral nutrition.

PMID- 16803601
TI  - Systematic review: does gastro-oesophageal reflux disease progress?
AB  - BACKGROUND: Gastro-oesophageal reflux disease affects approximately 20% of
      western populations. Barrett's oesophagus, associated with severe gastro
      oesophageal reflux disease, is premalignant and regular endoscopic surveillance
      is generally performed. In contrast, mild gastro-oesophageal reflux disease is
      thought not to progress and is not generally subjected to endoscopic follow-up.
      Aim To investigate whether gastro-oesophageal reflux disease progresses
      endoscopically. METHODS: Systematic review of the literature. RESULTS: Well
      designed prospective studies are few, diagnostic criteria were not always
      standardized, management strategies varied and various sources of bias could not
      be excluded. Whilst most patients do not progress to more severe forms of gastro
      oesophageal reflux disease, and some cases actually regress, progression is seen
      in a small proportion of patients. Annual progression rates for non-erosive
      gastro-oesophageal reflux disease developing erosive oesophagitis ranged from 0%
      to 30%. About 1-22% of patients with mild erosive oesophagitis developed more
      severe inflammation annually, while 1-13% of patients with erosive oesophagitis
      developed Barrett's oesophagus each year. CONCLUSION: Although most patients with
      gastro-oesophageal reflux disease do not progress, and some actually regress,
      progression does occur in a minority. Better data are required to determine
      whether patients with mild gastro-oesophageal reflux disease would benefit from
      increased surveillance with the aim of detecting more advanced disease.

PMID- 16803602
TI  - Systematic review: the use of serology to exclude or diagnose coeliac disease (a
      comparison of the endomysial and tissue transglutaminase antibody tests).
AB  - BACKGROUND: With the appreciation of the high prevalence of coeliac disease there
      is increasing use of serology in screening asymptomatic people and testing those
      with suggestive features. AIM: To compare the sensitivities and specificities of
      the endomysial antibody and the tissue transglutaminase antibody tests. METHODS:
      Using electronic databases a search was made for relevant papers using the terms
      tissue transglutaminase and endomysial antibody. RESULTS: Both the endomysial
      antibody and tissue transglutaminase antibody have very high sensitivities (93%
      for both) and specificities (>99% and >98% respectively) for the diagnosis of
      typical coeliac disease with villous atrophy. Human recombinant tissue
      transglutaminase performs much better than guinea pig tissue transglutaminase.
      Review of studies comparing endomysial antibody with human recombinant tissue
      transglutaminase antibody shows that endomysial antibody more often has a higher
      specificity and human recombinant tissue transglutaminase antibody more often has
      a higher sensitivity. CONCLUSION: The human recombinant tissue transglutaminase
      antibody is the preferred test for screening asymptomatic people and for
      excluding coeliac disease in symptomatic individuals with a low pretest
      probability (i.e. <25%) for coeliac disease. Furthermore, it has a number of
      practical and financial advantages. If the pretest probability is >25%, biopsy is
      preferred as the post-test probability of coeliac disease with a negative test is
      still >2%.

PMID- 16803603
TI  - Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro
      oesophageal reflux disease in Western patients with non-ulcer dyspepsia.
AB  - BACKGROUND: The effect of Helicobacter pylori eradication on the development of
      gastro-oesophageal reflux disease is controversial. Aim To determine the
      incidence of symptoms of reflux disease and of erosive oesophagitis, and the
      relationship to changes in histological gastritis, in patients with non-ulcer
      dyspepsia over 12 months. METHODS: Six hundred and ninety-three patients in two
      similar randomized placebo controlled trials of H. pylori eradication in non
      ulcer dyspepsia were studied. Symptoms were assessed using the validated
      Gastrointestinal Symptom Rating Scale during a 1-week run-in period, at 6 months
      and 12 months. Endoscopy was performed at baseline to exclude patients with
      pathology and at 3 months and 12 months to determine if oesophagitis was present.
      Gastric biopsies were scored using the modified Sydney Classification. RESULTS:
      Patients without predominant heartburn, oesophagitis or ulcers at endoscopy were
      randomized to active (n = 297, omeprazole, amoxicillin and clarithromycin)
      treatment or to placebo/omeprazole (n = 306) for 1 week. The eradication rate was
      82% in the active treatment group. Antrum-predominant gastritis (55%) was more
      frequently found than corpus-predominant gastritis (6%). In patients with antrum
      predominant gastritis, heartburn and regurgitation scores improved significantly
      12 months after eradication. Erosive oesophagitis developed in 15/232 patients in
      the eradication group (7%) compared with 2/227 (2%) in the control group, but
      there was no significant difference when adjusted for oesophagitis present at
      baseline. CONCLUSIONS: Antrum-predominant gastritis is the most common pattern of
      gastritis seen in non-ulcer dyspepsia in Western populations. Heartburn and
      regurgitation improve after eradication therapy or placebo in patients with non
      ulcer dyspepsia; the development of oesophagitis is uncommon.

PMID- 16803604
TI  - Recent trends in hospital admissions and mortality rates for peptic ulcer in
      Scotland 1982-2002.
AB  - BACKGROUND: While overall hospital admission rates for peptic ulcer declined in
      England in the 1990 s, they increased among the elderly, especially for
      complicated ulcer. However, peptic ulcer admissions fell for all age groups in
      the United States. AIM: To examine time trends in the incidence of hospital
      admissions, mortality and operations because of peptic ulcer in Scotland from
      1982 to 2002, and the use of various drugs relevant to the aetiology and
      treatment of peptic ulcer from 1992 to 2002. RESULTS: There was a general
      decrease in admission rates, especially for younger individuals. For individuals
      aged above 74 years, admission rates actually increased for gastric ulcer with
      haemorrhage among men, and for duodenal ulcer haemorrhage between both sexes. The
      number of operations fell dramatically, especially for younger patients.
      Mortality rates generally declined. Case fatality rates were greater for women
      than men, and declined over the study period for gastric ulcer, but increased for
      duodenal ulcer. The use of low-dose aspirin, oral anticoagulants, selective
      serotonin reuptake inhibitors and proton-pump inhibitors increased while those of
      non-steroidal anti-inflammatory drugs and histamine-2 antagonists declined.
      CONCLUSIONS: Admission rates for peptic ulcer generally fell for younger
      individuals, but increased for older people with haemorrhage.

PMID- 16803606
TI  - The epidemiology of pancreatic cancer in the United States: changes below the
      surface.
AB  - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer death in the
      United States. AIM: To examine temporal changes in the incidence and survival of
      patients with pancreatic adenocarcinoma. METHODS: Using data from nine registries
      of the Surveillance, Epidemiology and End Results programme, age-adjusted
      incidence rates per 100 000 and survival rates were calculated for pancreatic
      cancer between 1977 and 2001. RESULTS: We identified 58 655 cases of pancreatic
      cancer. The age-adjusted incidence rate remained stable during the study period
      (11.3 in 1977-1981 and 10.9 in 1997-2001). Overall, men were 30% more affected
      than women (age-adjusted incidence rate of 13.0 in men and 9.8 in women). The age
      adjusted incidence rates were almost 50% higher among Blacks (16.4) than Whites
      (10.8) and people of other races (9.8). Over time the proportions of patients
      with localized disease decreased from 12.3% to 7.4% and those with regional
      disease increased from 18.6% to 25.8%, while metastatic disease remained stable
      (52.5% vs. 49.8%). The 1-year relative survival increased from 15.2% in 1977-1981
      to 21.6% in 1997-2001. CONCLUSIONS: The incidence of pancreatic cancer is stable.
      A shift from localized to regional disease was observed over time. The overall
      survival remains poor despite important improvements among patients with early
      stage disease.

PMID- 16803605
TI  - Seven-day is more effective than 4-day ranitidine bismuth citrate-based triple
      therapy in eradication of Helicobacter pylori in children: a prospective
      randomized study.
AB  - BACKGROUND: Helicobacter pylori infection is common in paediatric population. To
      date, there is still no universally accepted recommendation on the treatment of
      this infection in children. Ranitidine bismuth citrate-based triple therapy has
      been shown to be effective in H. pylori eradication in adults but its use has
      rarely been validated in children. AIM: To investigate the efficacy of ranitidine
      bismuth citrate-based triple therapy in eradication of H. pylori in children and
      to determine the shortest duration of treatment required. PATIENTS AND METHODS:
      We conducted a prospective randomized study comparing ranitidine bismuth citrate
      plus amoxicillin plus clarithromycin given for 4 days vs. 7 days in H. pylori
      infected children diagnosed by (13)C-urea breath test. Eradication was evaluated
      by repeat (13)C-urea breath test at 6 weeks after treatment. RESULTS: A total of
      206 children were recruited (median age 12 years, 97 boys and 109 girls). Ninety
      eight (47.6%) and 108 (52.4%) children were randomized to receive 7-day and 4-day
      regimen respectively. The eradication rate of 4-day treatment arm was 77.8% (both
      intention-to-treat and per protocol) compared with 88.8% (intention-to-treat, P =
      0.036) and 89.7% (per protocol, P = 0.022) of 7-day regimen. There was no
      statistical difference in terms of side effects between the two groups.
      CONCLUSIONS: Seven-day ranitidine bismuth citrate-based triple therapy is an
      effective and well-tolerated treatment for eradication of H. pylori in children.

PMID- 16803607
TI  - Effect of oral clarithromycin on gall-bladder motility in normal subjects and
      those with gall-stones.
AB  - BACKGROUND: Motilin receptor stimulation with erythromycin has been shown to have
      a prokinetic effect on gall-bladder motility in human beings. AIM: To find out
      whether oral clarithromycin has similar prokinetic activity to erythromycin on
      fasting and postprandial gall-bladder emptying in normal humans and those with
      gall-stone disease. METHODS: In a blinded two-way crossover study clarithromycin
      500 mg and a placebo were administered to 10 normal subjects and 10 subjects with
      gall-stone disease. Gall-bladder volumes were assessed in the fasting and
      postprandial state. RESULTS: Fasting volumes were significantly less following
      clarithromycin administration in both normal subjects and subjects with gall
      stones compared with placebo (12.1 +/- 1.8 mL vs. 17.8 +/- 2.0 mL, P < 0.05 and
      16.7 +/- 2 mL vs. 26.8 +/- 7.2 mL, P < 0.02, mean +/- S.E.M). Postprandial
      volumes were also significantly less following clarithromycin administration.
      Ejection fraction significantly increased following clarithromycin in both normal
      subjects (66 +/- 5.8% vs. 37 +/- 5.9%, P = 0.02) and subjects with gall-stones
      (45 +/- 3.2 vs. 20 +/- 1.6%, P < 0.02). CONCLUSION: Clarithromycin enhances both
      fasting and postprandial gall-bladder contraction in normal humans and also in
      those with gall-stone disease.

PMID- 16803608
TI  - Low compliance with colonoscopic screening in first-degree relatives of patients
      with large adenomas.
AB  - BACKGROUND: Little is known about compliance with colonoscopy as a screening
      method in first-degree relatives of patients with large adenomas. Aims To
      evaluate the compliance with screening colonoscopy among this population, and its
      determinants. METHODS: Data were obtained from the family part of the GEADE
      study, a study on genetic factors of colorectal adenomas. Index cases were 306
      patients with adenomas > or = 10 mm. All living first-degree relatives aged 40-75
      who could be contacted by the index case were asked to undergo a colonoscopy,
      unless they had had one in the previous 5 years. RESULTS: Among 674 eligible
      relatives, 56 had had a colonoscopy within the preceding 5 years and 114
      underwent a screening colonoscopy resulting in a compliance with screening
      colonoscopy of 18%. This was not related to most characteristics of index cases.
      Compliance was significantly lower when the index case lived in the Greater Paris
      area than when he/she lived in other areas (12% vs. 21%). It was higher in
      siblings (18%) and offspring (23%) than in parents (9%) and in relatives under 55
      years old (22%) than in relatives aged 55 and over (15%). CONCLUSIONS: Compliance
      with colonoscopy was low in first-degree relatives of patients with large
      adenomas. The reasons for this should be determined and appropriate strategies
      developed to increase compliance.

PMID- 16803609
TI  - Newer cyclo-oxygenase-2 selective inhibitors, other non-steroidal anti
      inflammatory drugs and the risk of acute pancreatitis.
AB  - BACKGROUND: Case reports have suggested that the use of newer cyclo-oxygenase-2
      selective inhibitors may cause acute pancreatitis, but there has been no formal
      study of the association. AIM: To assess the relationship between the use of
      cyclo-oxygenase-2 inhibitors and other non-steroidal anti-inflammatory drugs, and
      risk of acute pancreatitis. METHODS: A population-based case-control study was
      conducted using hospital discharge and prescription data from Denmark. Using
      conditional logistic regression with adjustment for multiple covariates, we
      estimated the relative risk of acute pancreatitis for use of the cyclo-oxygenase
      2 inhibitors celecoxib and rofecoxib and for other non-steroidal anti
      inflammatory drugs. RESULTS: A total of 3083 cases of acute pancreatitis and 30
      830 population controls were identified. For current use the relative risk
      estimate for celecoxib was 1.4 (95% CI: 0.8-2.3) and for rofecoxib was 1.3 (95%
      CI: 0.7-2.3). The overall relative risk for other non-steroidal anti-inflammatory
      drugs was 2.7 (95% CI: 2.4-3.0) with a substantial variation in risk between the
      individual drugs. The highest relative risk was for diclofenac (odds ratio 5.0,
      95% CI: 4.2-5.9) and the lowest for naproxen (odds ratio 1.1, 95% CI: 0.7-1.7).
      CONCLUSION: Cyclo-oxygenase-2 selective inhibitors are associated with a lower
      risk of acute pancreatitis than most other non-steroidal anti-inflammatory drugs.

PMID- 16803610
TI  - Sustained virological response to peginterferon plus ribavirin in chronic
      hepatitis C genotype 1 patients is associated with a persistent Th1 immune
      response.
AB  - BACKGROUND: An impairment of cellular immune response may contribute to the
      persistency of hepatitis C virus infection. AIM: To analyse the Th1/Th2 cytokine
      profile in peripheral blood CD4(+) and CD8(+) T cells from patients with chronic
      hepatitis C (CHC) during treatment with pegylated interferon-alpha2a plus
      ribavirin and to correlate the Th1/Th2 balance with virological response (SVR).
      METHODS: Prospective longitudinal study: 44 naive genotype 1 CHC patients
      received PEG-IFNalpha2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR,
      13 relapsed (29.5%) and 5 (11.4%) were non-responders. Sixteen healthy controls
      were analysed. The production of IL-4, IFNgamma and TNFalpha by CD4(+) and CD8(+)
      T cells was measured using flow cytometry, both in resting and phorbol-ester
      stimulated cells. RESULTS: First three months of treatment: the synthesis of
      TNFalpha by phorbol-ester-stimulated-CD4(+) T cells was higher in patients with
      SVR (P < 0.01). At the end of treatment, SVR was associated with higher
      intracellular expression of IFNgamma by stimulated-CD4(+) and CD8(+) T cells (P <
      0.05). At the end of follow-up, a higher intracellular expression of IFNgamma by
      CD4(+) T cells was associated with a SVR. CONCLUSIONS: A Th1-type immune response
      was associated with achievement of a SVR, as indicated by the persistent
      elevation of intracellular IFNgamma and TNFalpha.

PMID- 16803611
TI  - A statistical model predicting high hepatocyte proliferation index and the risk
      of developing hepatocellular carcinoma in patients with hepatitis C virus-related
      cirrhosis.
AB  - BACKGROUND: Incidence of hepatocellular carcinoma in hepatitis C virus-related
      cirrhosis is 4% per year. Although cost-effective, current screening could be
      improved. AIM: To develop a statistical model including non-invasive parameters
      able to identify patients at high risk of developing hepatocellular carcinoma.
      METHODS: One hundred and fifty-eight patients (73F:85M) with compensated chronic
      hepatitis C virus liver disease underwent evaluation, including argyrophilic
      nucleolar organizer regions proliferation index, and were followed up for 56.18
      +/- 1.44 months. RESULTS: Fifty-six patients had chronic hepatitis without
      cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (<
      or =25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic
      nucleolar organizer regions proliferation index and 37 had hepatitis C virus
      related cirrhosis and high argyrophilic nucleolar organizer regions proliferation
      index (>25%). Groups were similar for gender and viral genotype distribution.
      None of the patients with chronic hepatitis without cirrhosis developed
      hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar
      organizer regions proliferation index and 30.6% of high argyrophilic nucleolar
      organizer regions proliferation index (P = 0.002). By multivariable logistic
      regression analysis, the following parameters were independently associated with
      hepatocellular carcinoma development and used for the development of the
      statistical model: platelets (OR 0.98), gamma-globulins (OR 0.111), alanine
      aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR
      1.0) and ultrasonographic pattern (coarse OR 2.9, coarse nodular OR 10.12). The
      statistical model properly allocated 95.9% of patients with low argyrophilic
      nucleolar organizer regions proliferation index and 72.2% of patients with high
      argyrophilic nucleolar organizer regions proliferation index. CONCLUSIONS: The
      model, to be validated in large prospective studies, may help tailoring screening
      according to the risk of hepatocellular carcinoma development.

PMID- 16803612
TI  - Utility of red flag symptom exclusions in the diagnosis of irritable bowel
      syndrome.
AB  - BACKGROUND: Studies suggest that the positive predictive value of the Rome II
      criteria for diagnosing irritable bowel syndrome can be enhanced by excluding red
      flag symptoms suggestive of organic diseases. AIM: We assessed the utility of red
      flags for detecting organic diseases in patients diagnosed irritable bowel
      syndrome by their physicians. METHODS: Systematic chart reviews were completed in
      1434 patients with clinical diagnoses of irritable bowel syndrome, abdominal
      pain, diarrhoea or constipation, who also completed questionnaires to identify
      Rome II criteria for irritable bowel syndrome and red flag symptoms. RESULTS: The
      overall incidence of gastrointestinal cancer was 2.5% (but 1.0% in those with
      irritable bowel syndrome), for inflammatory bowel disease 2.0% (1.2% in irritable
      bowel syndrome), and for malabsorption 1.3% (0.7% in irritable bowel syndrome).
      Red flags were reported by 84% of the sample. The positive predictive value of
      individual red flags for identifying organic disease was 7-9%. Excluding any
      patient with a red flag improved the agreement between Rome II and clinical
      diagnosis by a modest 5%, but left 84% of patients who were diagnosed with
      irritable bowel syndrome by their physicians, without a diagnosis. CONCLUSIONS:
      Red flags may be useful for identifying patients who require additional
      diagnostic evaluation, but incorporating them into the Rome criteria would not
      improve sensitivity and would result in too many missed irritable bowel syndrome
      diagnoses.

PMID- 16803613
TI  - Self transglutaminase-based rapid coeliac disease antibody detection by a lateral
      flow method.
AB  - BACKGROUND: The conventional coeliac disease antibody tests require patient's
      sera, and are laborious and time-consuming. AIM: To evaluate a newly developed
      rapid whole blood test in coeliac disease antibody detection, and its suitability
      for office use. METHODS: Endogenous tissue transglutaminase found in red blood
      cells in a whole blood fingertip or venous sample is liberated upon haemolysis
      and complexes with tissue transglutaminase antibodies, if present. The complexes,
      captured by a lateral flow system, are visualized within 5 min. Stored samples
      from 121 untreated, 106 treated coeliac disease patients and 107 controls were
      evaluated and compared with serum endomysium and tissue transglutaminase antibody
      tests and histology; 150 patients were prospectively tested on site in the
      doctor's office. RESULTS: The rapid test showed sensitivity (96.7%) comparable
      with the serum endomysium and tissue transglutaminase antibody tests from stored
      samples; specificity was slightly lower (93.5%). When tested on site the results
      were concordant in 96.7% of cases compared with endomysium and tissue
      transglutaminase antibody results. The test recognized the disappearance of
      tissue transglutaminase antibodies on a gluten-free diet. CONCLUSIONS: The self
      tissue transglutaminase-based rapid test can be easily carried out from a
      fingertip blood sample on site in the physician's office for both coeliac disease
      case finding and dietary monitoring purposes.

PMID- 16803614
TI  - Effects of a 5-HT(4) receptor agonist on oesophageal function and gastro
      oesophageal reflux: studies using combined impedance-manometry and combined
      impedance-pH.
AB  - BACKGROUND: 5-HT(4) receptor agonists are used as promotility agents of the
      stomach, small and large intestine. There is limited information on the influence
      of 5-HT(4) receptor agonists on oesophageal function and gastro-oesophageal
      reflux. AIM: To evaluate the effects of tegaserod, a 5-HT(4) agonist on
      oesophageal function using impedance-manometry and postprandial reflux using
      impedance-pH monitoring. METHODS: Twenty healthy volunteers were enrolled in a
      double-blind randomized three-period crossover placebo-controlled study.
      Impedance-manometry and impedance-pH monitoring after a refluxogenic meal were
      performed at baseline and after 2 days of dosing with tegaserod 6 mg b.d. or
      placebo. Multichannel intraluminal impedance-EM recorded pressure and bolus
      transit data during standardized swallows. Multichannel intraluminal impedance-pH
      monitoring recorded the number of 2-h postprandial acid and non-acid reflux
      episodes. RESULTS: We found no significant difference in distal oesophageal
      amplitude when subjects received placebo (median 94.5; range: 53-243 mmHg) or
      tegaserod (93.6; 43-216 mmHg). Bolus transit time was similar during dosing with
      placebo (7.1; 5.3-9.4 s) and tegaserod (7.2; 5.9-11.1 s). We observed similar
      numbers of acid and non-acid reflux episodes during dosing with placebo (5; 0-15
      and 3; 0-18, respectively) and tegaserod (2; 0-11 and 4; 0-19, respectively).
      CONCLUSION: Tegaserod, a 5-HT(4) receptor agonist does not change oesophageal
      motility and gastro-oesophageal reflux parameters in healthy volunteers.

PMID- 16803615
TI  - Novel knowledge-based mean force potential at the profile level.
AB  - BACKGROUND: The development and testing of functions for the modeling of protein
      energetics is an important part of current research aimed at understanding
      protein structure and function. Knowledge-based mean force potentials are derived
      from statistical analyses of interacting groups in experimentally determined
      protein structures. Current knowledge-based mean force potentials are developed
      at the atom or amino acid level. The evolutionary information contained in the
      profiles is not investigated. Based on these observations, a class of novel
      knowledge-based mean force potentials at the profile level has been presented,
      which uses the evolutionary information of profiles for developing more powerful
      statistical potentials. RESULTS: The frequency profiles are directly calculated
      from the multiple sequence alignments outputted by PSI-BLAST and converted into
      binary profiles with a probability threshold. As a result, the protein sequences
      are represented as sequences of binary profiles rather than sequences of amino
      acids. Similar to the knowledge-based potentials at the residue level, a class of
      novel potentials at the profile level is introduced. We develop four types of
      profile-level statistical potentials including distance-dependent, contact,
      Phi/Psi dihedral angle and accessible surface statistical potentials. These
      potentials are first evaluated by the fold assessment between the correct and
      incorrect models generated by comparative modeling from our own and other groups.
      They are then used to recognize the native structures from well-constructed decoy
      sets. Experimental results show that all the knowledge-base mean force potentials
      at the profile level outperform those at the residue level. Significant
      improvements are obtained for the distance-dependent and accessible surface
      potentials (5-6%). The contact and Phi/Psi dihedral angle potential only get a
      slight improvement (1-2%). Decoy set evaluation results show that the distance
      dependent profile-level potentials even outperform other atom-level potentials.
      We also demonstrate that profile-level statistical potentials can improve the
      performance of threading. CONCLUSION: The knowledge-base mean force potentials at
      the profile level can provide better discriminatory ability than those at the
      residue level, so they will be useful for protein structure prediction and model
      refinement.

PMID- 16803616
TI  - Plasma levels of soluble tumor necrosis factor-alpha receptors are related to
      total and LDL-cholesterol in lean, but not in obese subjects.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNFalpha) is a mediator of insulin
      resistance. Plasma levels of soluble TNFalpha receptors (sTNFR1 and sTNFR2)
      probably reflect paracrine action of the cytokine. TNFalpha is also a regulator
      of lipid metabolism, however, data about impact of obesity on the relationships
      between TNFalpha and plasma lipids remain controversial. AIM: The purpose of the
      present study was to examine the associations of TNFalpha system with plasma
      lipids in lean and obese subjects with normal glucose metabolism. METHODS: We
      examined 63 subjects, 33 lean (BMI<25 kg x m(-2)) and 30 with marked overweight
      or obesity (BMI>27.8 kg x m(-2)). Anthropometric and biochemical parameters were
      measured. Oral glucose tolerance test and euglycemic hyperinsulinemic clamp were
      also performed. RESULTS: Obese subjects were markedly more insulin resistant and
      had higher levels of both TNFalpha receptors. Total (TC) and LDL-cholesterol (LDL
      C), triglycerides (TG) and non-esterified fatty acids (NEFA) were also higher in
      the obese group. In obese subjects, both receptors were significantly related to
      TG and HDL-cholesterol (HDL-C), while sTNFR2 was also associated with NEFA. All
      those correlations disappeared after controlling for insulin sensitivity. In lean
      subjects, both receptors were related to TC, HDL-C and LDL-C. In that group,
      sTNFR1 predicted values of all those parameters independently of BMI, plasma
      glucose and insulin, and insulin sensitivity. CONCLUSION: We conclude that
      TNFalpha receptors are associated with plasma lipids in different way in lean and
      in obese subjects. TNFalpha system is probably important in determining
      cholesterol levels in lean subjects, while in obese this effect might be masked
      by other metabolic abnormalities.

PMID- 16803617
TI  - The Autoimmune Disease Database: a dynamically compiled literature-derived
      database.
AB  - BACKGROUND: Autoimmune diseases are disorders caused by an immune response
      directed against the body's own organs, tissues and cells. In practice more than
      80 clinically distinct diseases, among them systemic lupus erythematosus and
      rheumatoid arthritis, are classified as autoimmune diseases. Although their
      etiology is unclear these diseases share certain similarities at the molecular
      level i.e. susceptibility regions on the chromosomes or the involvement of common
      genes. To gain an overview of these related diseases it is not feasible to do a
      literary review but it requires methods of automated analyses of the more than
      500,000 Medline documents related to autoimmune disorders. RESULTS: In this paper
      we present the first version of the Autoimmune Disease Database which to our
      knowledge is the first comprehensive literature-based database covering all known
      or suspected autoimmune diseases. This dynamically compiled database allows
      researchers to link autoimmune diseases to the candidate genes or proteins
      through the use of named entity recognition which identifies genes/proteins in
      the corresponding Medline abstracts. The Autoimmune Disease Database covers 103
      autoimmune disease concepts. This list was expanded to include synonyms and
      spelling variants yielding a list of over 1,200 disease names. The current
      version of the database provides links to 541,690 abstracts and over 5,000 unique
      genes/proteins. CONCLUSION: The Autoimmune Disease Database provides the
      researcher with a tool to navigate potential gene-disease relationships in
      Medline abstracts in the context of autoimmune diseases.

PMID- 16803618
TI  - Beta-lactam antibiotic-induced release of lipoteichoic acid from Staphylococcus
      aureus leads to activation of neutrophil granulocytes.
AB  - BACKGROUND: Polymorphonuclear neutrophil granulocytes (PMN) are phagocytes of the
      first line of antimicrobial defense. Previously we demonstrated that lipoteichoic
      acid (LTA) from Staphylococcus aureus (S. aureus) directly activates neutrophil
      granulocytes. Others have reported that exposure of S. aureus to beta-lactam
      antibiotics leads to LTA release. In the present study we addressed the question
      whether exposure of S. aureus to beta-lactam antibiotics or antibiotics of other
      groups results in the generation of PMN-stimulating activity and whether this
      activity can be attributed to LTA. METHODS: S. aureus were exposed to
      flucloxacillin, a beta-lactam antibiotic or to the protein synthesis-inhibitors
      erythromycin and gentamicin, or to ciprofloxacin, a gyrase inhibitor.
      Supernatants of the antibiotic-treated bacteria were assayed for their LTA
      content and for their effect on PMN functions. RESULTS: We observed that exposure
      of S. aureus to flucloxacillin and, to a lesser degree to ciprofloxacin, but not
      to erythromycin or gentamicin led to LTA release. Co-incubation of neutrophil
      granulocytes with LTA-containing supernatants led to PMN activation as assed by
      morphological changes, release of IL-8, delay of spontaneous apoptosis and
      enhanced phagocytic activity. Depletion of LTA from the supernatants markedly
      reduced their PMN-activating capacity. CONCLUSION: The findings suggest that, via
      the activation of PMN, antibiotic-induced LTA release from S. aureus leads to
      enhanced antimicrobial activity of the innate immune defense mechanisms.

PMID- 16803619
TI  - Interleukin-10 polymorphisms in Spanish IgA deficiency patients: a case-control
      and family study.
AB  - BACKGROUND: IgA deficiency (IgAD) is the most common primary immunodeficiency in
      Caucasians. Genetic and environmental factors are suspected to be involved in the
      development of the disease. Interleukin-10 (IL-10) is a cytokine with stimulatory
      activity on immunoglobulin production and it may be an important regulator in
      IgAD pathogenesis. The IL-10 gene contains several single nucleotide
      polymorphisms (SNPs) and two polymorphic microsatellites located in the 5'
      flanking region. Our aim was to ascertain if any of these polymorphic markers are
      associated or linked to IgAD in Spanish patients. METHODS: We genotyped 278
      patients with IgAD and 573 ethnically matched controls for the microsatellites IL
      10R and IL-10G and for three single nucleotide polymorphisms at positions -1082, 
      819 and -592 in the proximal promoter of the gene. We also included in this study
      the parents of 194 patients in order to study the IL-10 haplotypes transmitted
      and not transmitted to the affected offspring. RESULTS: The only allele where a
      significant difference was observed in the comparison between IgA deficiency
      patients and controls was the IL-10G12 allele (OR = 1.58 and p = 0.021). However,
      this p value could not withstand a Bonferroni correction. None of the IL-10R or
      promoter SNP alleles was found at a different frequency when patients were
      compared with controls. CONCLUSION: Our data do not show any significant
      difference in IL-10 polymorphism frequencies between control and IgAD patient
      samples. Their haplotype distribution among patients and controls was also
      equivalent and therefore these microsatellites and SNPs do not seem to influence
      IgAD susceptibility.

PMID- 16803620
TI  - Prevalence of diabetes, metabolic syndrome and metabolic abnormalities in
      schizophrenia over the course of the illness: a cross-sectional study.
AB  - BACKGROUND: Patients with schizophrenia are at high risk of developing metabolic
      abnormalities. METHOD: A prospective study focusing on metabolic disturbances in
      patients with schizophrenia, including an oral glucose tolerance test, is
      currently ongoing at our University Hospital and affiliate services. The
      prevalence of metabolic abnormalities at baseline was assessed in a cohort of 415
      patients with schizophrenia. The sample was divided into 4 groups according to
      duration of illness: first-episode patients (<1.5 years), recent-onset patients
      (between 1.5 and 10 years), subchronic patients (between 10 and 20 years) and
      chronic patients (>20 years). RESULTS: Metabolic abnormalities were already
      present in first-episode patients, and considerably increased with increasing
      duration of illness. When compared to the general population matched for age and
      gender, much higher rates of the metabolic syndrome (MetS) and diabetes were
      observed for patients with schizophrenia. For MetS, the increase over time was
      similar to that of the general population. In contrast, the difference in the
      prevalence of diabetes in patients with schizophrenia and the general population
      dramatically and linearly increased from 1.6% in the 15-25 age-band to 19.2% in
      the 55-65 age-band. CONCLUSION: Thus, the current data suggest that on the one
      hand metabolic abnormalities are an inherent part of schizophrenic illness, as
      they are already present in first-episode patients. On the other hand, however,
      our results suggest a direct effect of the illness and/or antipsychotic
      medication on their occurrence. The data underscore the need for screening for
      metabolic abnormalities in patients diagnosed with schizophrenia, already
      starting from the onset of the illness.

PMID- 16803622
TI  - Estimating the cost-effectiveness of detecting cases of chronic hepatitis C
      infection on reception into prison.
AB  - BACKGROUND: In England and Wales where less than 1% of the population are
      Injecting drug users (IDUs), 97% of HCV reports are attributed to injecting drug
      use. As over 60% of the IDU population will have been imprisoned by the age of 30
      years, prison may provide a good location in which to offer HCV screening and
      treatment. The aim of this work is to examine the cost effectiveness of a number
      of alternative HCV case-finding strategies on prison reception METHODS: A
      decision analysis model embedded in a model of the flow of IDUs through prison
      was used to estimate the cost effectiveness of a number of alternative case
      finding strategies. The model estimates the average cost of identifying a new
      case of HCV from the perspective of the health care provider and how these
      estimates may evolve over time. RESULTS: The results suggest that administering
      verbal screening for a past positive HCV test and for ever having engaged in
      illicit drug use prior to the administering of ELISA and PCR tests can have a
      significant impact on the cost effectiveness of HCV case-finding strategies on
      prison reception; the discounted cost in 2017 being pound2,102 per new HCV case
      detected compared to pound3,107 when no verbal screening is employed. CONCLUSION:
      The work here demonstrates the importance of targeting those individuals that
      have ever engaged in illicit drug use for HCV testing in prisons, these
      individuals can then be targeted for future intervention measures such as
      treatment or monitored to prevent future transmission.

PMID- 16803621
TI  - Clustering of smoking, alcohol drinking and cannabis use in adolescents in a
      rapidly developing country.
AB  - BACKGROUND: Smoking, alcohol drinking and cannabis use ("risk behaviors") are
      often initiated at a young age but few epidemiological studies have assessed
      their joined prevalence in children in developing countries. This study aims at
      examining the joint prevalence of these behaviors in adolescents in the
      Seychelles, a rapidly developing country in the Indian Ocean. METHODS: Cross
      sectional survey in a representative sample of secondary school students using an
      anonymous self-administered questionnaire (Global Youth Tobacco Survey). The
      questionnaire was completed by 1,321 (92%) of 1,442 eligible students aged 11 to
      17 years. Main variables of interest included smoking cigarettes on > or =1 day
      in the past 30 days; drinking any alcohol beverage on > or =1 day in the past 30
      days and using cannabis at least once in the past 12 months. RESULTS: In boys and
      girls, respectively, prevalence (95% CI) was 30% (26-34)/21% (18-25) for smoking,
      49% (45-54)/48% (43-52) for drinking, and 17% (15-20)/8% (6-10) for cannabis use.
      The prevalence of all these behaviors increased with age. Smokers were two times
      more likely than non-smokers to drink and nine times more likely to use cannabis.
      Drinkers were three times more likely than non-drinkers to smoke or to use
      cannabis. Comparison of observed versus expected frequencies of combination
      categories demonstrated clustering of these risk behaviors in students (P <
      0.001). CONCLUSION: Smoking, drinking and cannabis use were common and clustered
      among adolescents of a rapidly developing country. These findings stress the need
      for early and integrated prevention programs.

PMID- 16803623
TI  - Economic evaluation of a clinical protocol for diagnosing emergency patients with
      suspected pulmonary embolism.
AB  - BACKGROUND: The objective of this paper is to estimate the amount of cost-savings
      to the Australian health care system from implementing an evidence-based clinical
      protocol for diagnosing emergency patients with suspected pulmonary embolism (PE)
      at the Emergency department of a Victorian public hospital with 50,000
      presentations in 2001-2002. METHODS: A cost-minimisation study used the data
      collected in a controlled clinical trial of a clinical protocol for diagnosing
      patients with suspected PE. The number and type of diagnostic tests in a historic
      cohort of 185 randomly selected patients, who presented to the emergency
      department with suspected PE during an eight month period prior to the clinical
      trial (January 2002-August 2002) were compared with the number and type of
      diagnostic tests in 745 patients, who presented to the emergency department with
      suspected PE from November 2002 to August 2003. Current Medicare fees per test
      were used as unit costs to calculate the mean aggregated cost of diagnostic
      investigation per patient in both study groups. A t-test was used to estimate the
      statistical significance of the difference in the cost of resources used for
      diagnosing PE in the control and in the intervention group. RESULTS: The trial
      demonstrated that diagnosing PE using an evidence-based clinical protocol was as
      effective as the existing clinical practice. The clinical protocol offers the
      advantage of reducing the use of diagnostic imaging, resulting in an average cost
      savings of at least $59.30 per patient. CONCLUSION: Extrapolating the observed
      cost-savings of $59.30 per patient to the whole of Australia could potentially
      result in annual savings between $3.1 million to $3.7 million.

PMID- 16803624
TI  - Single-stage repair of adult aortic coarctation and concomitant cardiovascular
      pathologies: a new alternative surgical approach.
AB  - BACKGROUND: Coarctation of the aorta in the adulthood is sometimes associated
      with additional cardiovascular pathologies that require intervention. Ideal
      approach in such patients is uncertain. Anatomic left-sided short aortic bypass
      from the arcus aorta to descending aorta via median sternotomy allows
      simultaneous repair of both complex aortic coarctation and concomitant cardiac
      operation. MATERIALS: Four adult patients were underwent Anatomic left-sided
      short aortic bypass operation for complex aortic coarctation through median
      sternotomy using deep hypothermic circulatory arrest. Concomitant cardiac
      operations were Bentall procedure for annuloaortic ectasia in one patient,
      coronary artery bypass grafting for three vessel disease in two patient, and
      patch closure of ventricular septal defect in one patient. RESULTS: All patients
      survived the operation and were alive with patent bypass at a mean follow-up of
      36 months. No graft-related complications occurred, and there were no instances
      of stroke or paraplegia. CONCLUSION: We conclude that single-stage repair of
      adult aortic coarctation with concomitant cardiovascular lesions can be performed
      safely using this newest technique.

PMID- 16803625
TI  - Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication
      in HepG2 cells.
AB  - BACKGROUND: Hepatitis C (HCV) viral infection is a serious medical problem in
      Egypt and it has a devastating impact on the Egyptian economy. It is estimated
      that over 15% of Egyptians are infected by the virus and thus finding a cure for
      this disease is of utmost importance. Current therapies for hepatitis C virus
      (HCV) genotype 4 with interferon/ribavirin have not been successful and thus the
      development of alternative therapy for this genotype is desperately needed.
      RESULTS: Although previous studies utilizing viral subgenomic or full cDNA
      fragments linked to reporter genes transfected into adhered cells or in a cell
      free system showed promise, demonstration of efficient viral replication was
      lacking. Thus, we utilized HepG2 cells infected with native HCV RNA genomes in a
      replication competent system and used antisense phosphorothioate Oligonucleotides
      (S-ODN) against stem loop IIId and the AUG translation start site of the viral
      polyprotein precursor to monitor viral replication. We were able to show complete
      arrest of intracellular replication of HCV-4 at 1 uM S-ODN, thus providing a
      proof of concept for the potential antiviral activity of S-ODN on native genomic
      replication of HCV genotype 4. CONCLUSION: We have successfully demonstrated that
      by using two S-ODNs [(S-ODN1 (nt 326-348) and S-ODN-2 (nt 264-282)], we were able
      to completely inhibit viral replication in culture, thus confirming earlier
      reports on subgenomic constructs and suggesting a potential therapeutic value in
      HCV type 4.

PMID- 16803626
TI  - Cationic hydrous thorium dioxide colloids--a useful tool for staining negatively
      charged surface matrices of bacteria for use in energy-filtered transmission
      electron microscopy.
AB  - BACKGROUND: Synthesis of cationic hydrous thorium dioxide colloids (ca. 1.0 to
      1.7 nm) has been originally described by Muller 22 and Groot 11 and these have
      been used by Groot to stain acidic glucosaminoglycans for ultrastructure research
      of different tissues by conventional transmission electron microscopy. RESULTS:
      Synthesis of colloidal thorium dioxide has been modified and its use as a
      suitable stain of acidic mucopolysaccharides and other anionic biopolymers from
      bacteria, either as whole mount preparations or as preembedment labels, is
      described. The differences in stain behavior relative to commonly used
      rutheniumred-lysine and Alcian Blue electron dense acidic stains has been
      investigated and its use is exemplified for Pseudomonas aeruginosa adjacent cell
      wall biopolymers. For the first time thorificated biopolymers, i.e. bacterial
      outer cell wall layers, have been analysed at the ultrastructural level with
      electron energy loss spectroscopy (EELS) and electron spectroscopic imaging
      (ESI), leading to excellent contrast and signal strength for these extracellular
      biopolymers. CONCLUSION: Application of cationic hydrous ThO2 colloids for
      tracing acidic groups of the bacterial surface and/or EPS has been shown to be
      rather effective by transmission electron microscopy. Because of its high
      electron density and its good diffusibility it stains and outlines electro
      negative charges within these biopolymers. In combination with ESI, based on
      integrated energy-filtered electron microscopy (EFTEM) Th-densities and thus
      negative charge densities can be discriminated from other elemental densities,
      especially in environmental samples, such as biofilms.

PMID- 16803627
TI  - Association of umbilical cord blood lead with neonatal behavior at varying levels
      of exposure.
AB  - BACKGROUND: In the light of the ongoing debate about lowering the cut-off for
      acceptable blood lead level to <5 microg/dL from the currently recommended level
      of <10 microg/dL, we considered whether prenatal exposure to varying levels of
      lead is associated with similar or disparate effects on neonatal behavior.
      METHODS: Using Brazelton's Neonatal Behavioral Assessment Scale (NBAS), an
      epidemiological approach and robust statistical techniques like multivariate
      linear regression, logistic regression, Poisson regression and structural
      equations modeling analyses we estimated the simultaneous indirect effects of
      umbilical cord blood lead (CBL) levels and other neonatal covariates on the NBAS
      clusters. RESULTS: We observed that when analyzed in all study subjects, the CBL
      levels independently and strongly influenced autonomic stability and abnormal
      reflexes clusters. However, when the analysis was restricted to neonates with CBL
      <10 microg/dL, CBL levels strongly influenced the range of state, motor and
      autonomic stability clusters. Abnormal walking reflex was consistently associated
      with an increased CBL level irrespective of the cut-off for CBL, however, only at
      the lower cut-offs were the predominantly behavioral effects of CBL discernible.
      CONCLUSION: Our results further endorse the need to be cognizant of the
      detrimental effects of blood lead on neonates even at a low-dose prenatal
      exposure.

PMID- 16803628
TI  - Population attributable risk of breast cancer in white women associated with
      immediately modifiable risk factors.
AB  - BACKGROUND: Estrogen/progestin replacement therapy (EPRT), alcohol consumption,
      physical activity, and breast-feeding duration differ from other factors
      associated with breast cancer in being immediately modifiable by the individual,
      thereby representing attractive targets for future breast cancer prevention
      efforts. To justify such efforts, it is vital to quantify the potential
      population-level impacts on breast cancer considering population variations in
      behavior prevalence, risk estimate, and baseline incidence. METHODS: For each of
      these four factors, we calculated population attributable risk percents (PARs)
      using population-based survey (2001) and cancer registry data (1998-2002) for 41
      subpopulations of white, non-Hispanic California women aged 40-79 years, and
      ranges of relative risk (RR) estimates from the literature. RESULTS: Using a
      single RR estimate, subpopulation PARs ranged from 2.5% to 5.6% for hormone use,
      from 0.0% to 6.1% for recent consumption of > or = 2 alcoholic drinks daily, and
      4.6% to 11.0% for physical inactivity. Using a range of RR estimates, PARs were 2
      11% for EPRT use, 1-20% for alcohol consumption and 2-15% for physical
      inactivity. Subpopulation data were unavailable for breastfeeding, but PARs using
      published RR estimates ranged from 2% to 11% for lifetime breastfeeding > or = 31
      months. Thus, of 13,019 breast cancers diagnosed annually in California, as many
      as 1,432 attributable to EPRT use, 2,604 attributable to alcohol consumption,
      1,953 attributable to physical inactivity, and 1,432 attributable to never
      breastfeeding might be avoidable. CONCLUSION: The relatively feasible lifestyle
      changes of discontinuing EPRT use, reducing alcohol consumption, increasing
      physical activity, and lengthening breastfeeding duration could lower population
      breast cancer incidence substantially.

PMID- 16803629
TI  - Identification of novel mutant PAX6 alleles in Indian cases of familial aniridia.
AB  - BACKGROUND: Haploinsufficiency at the PAX6 locus causes aniridia, a panocular eye
      condition characterized by iris hypoplasia and a variety of other anterior and
      posterior eye defects leading to poor vision. This study was performed to
      identify novel PAX6 mutations that lead to familial aniridia in Indian patients.
      METHODS: Genomic DNA was isolated from affected individuals (clinically diagnosed
      aniridia) from nine unrelated aniridic pedigrees, unaffected family members, and
      unrelated normal controls. The coding regions of PAX6 were amplified and
      subjected to single strand conformation polymorphism (SSCP) gel analysis, and
      direct cloning and sequencing. RESULTS: SSCP band shifts, indicative of DNA base
      pair mutations, were observed in five of these unrelated families. Four mutations
      were shown to be previously unreported insertion or deletions in PAX6, leading to
      frameshifts. These new mutations were c.1174delTG (in exon 10), c.710delC (exon
      6), c.406delTT (exon 5) and c.393insTCAGC (exon 5). The other nonsense mutation,
      a transition (c.1080C>T) in exon 9, has been reported previously as a mutation
      hotspot for PAX6 in other ethnic pedigrees. All mutant alleles transmitted
      through aniridic individuals in each family. CONCLUSION: These new deletions and
      an insertion create frameshifts, which are predicted to introduce premature
      termination codons into the PAX6 reading frame. The genetic alterations carried
      by affected individuals are predicted to lead to loss-of-function mutations that
      would segregate in an autosomal dominant manner to subsequent generations. This
      is the first report of the 'hotspot' c.1080C>T transition from Indian families.

PMID- 16803631
TI  - SUP: an extension to SLINK to allow a larger number of marker loci to be
      simulated in pedigrees conditional on trait values.
AB  - BACKGROUND: With the recent advances in high-throughput genotyping technologies
      that allow for large-scale association mapping of human complex traits, promising
      statistical designs and methods have been emerging. Efficient simulation software
      are key elements for the evaluation of the properties of new statistical tests.
      SLINK is a flexible simulation tool that has been widely used to generate the
      segregation and recombination processes of markers linked to, and possibly
      associated with, a trait locus, conditional on trait values in arbitrary
      pedigrees. In practice, its most serious limitation is the small number of loci
      that can be simulated, since the complexity of the algorithm scales exponentially
      with this number. RESULTS: I describe the implementation of a two-step algorithm
      to be used in conjunction with SLINK to enable the simulation of a large number
      of marker loci linked to a trait locus and conditional on trait values in
      families, with the possibility for the loci to be in linkage disequilibrium.
      SLINK is used in the first step to simulate genotypes at the trait locus
      conditional on the observed trait values, and also to generate an indicator of
      the descent path of the simulated alleles. In the second step, marker alleles or
      haplotypes are generated in the founders, conditional on the trait locus
      genotypes simulated in the first step. Then the recombination process between the
      marker loci takes place conditionally on the descent path and on the trait locus
      genotypes. This two-step implementation is often computationally faster than
      other software that are designed to generate marker data linked to, and possibly
      associated with, a trait locus. CONCLUSION: Because the proposed method uses
      SLINK to simulate the segregation process, it benefits from its flexibility: the
      trait may be qualitative with the possibility of defining different liability
      classes (which allows for the simulation of gene-environment interactions or even
      the simulation of multi-locus effects between unlinked susceptibility regions) or
      it may be quantitative and normally distributed. In particular, this
      implementation is the only one available that can generate a large number of
      marker loci conditional on the set of observed quantitative trait values in
      pedigrees.

PMID- 16803630
TI  - The ability of flagellum-specific Proteus vulgaris bacteriophage PV22 to interact
      with Campylobacter jejuni flagella in culture.
AB  - BACKGROUND: There has been a recent resurgent interest in bacteriophage biology.
      Research was initiated to examine Campylobacter jejuni-specific bacteriophage in
      the Russian Federation to develop alternative control measures for this pathogen.
      RESULTS: A C. jejuni flagellum-specific phage PV22 from Proteus vulgaris was
      identified in sewage drainage. This phage interacted with C. jejuni by attachment
      to flagella followed by translocation of the phage to the polar region of the
      bacterium up to the point of DNA injection. Electron microscopic examination
      revealed adsorption of PV22 on C. jejuni flagella after a five minute incubation
      of the phage and bacteria. A different phenomenon was observed after incubating
      the mix under the same conditions, but for twenty minutes or longer. Phage
      accumulated primarily on the surface of cells at sites where flagella originated.
      Interestingly, PV22 did not inject DNA into C. jejuni and PV22 did not produce
      lytic plaques on medium containing C. jejuni cells. The constant of velocity for
      PV22 adsorption on cells was 7 x 10(-9) ml/min. CONCLUSION: It was demonstrated
      that a bacteriophage that productively infects P. vulgaris was able to bind C.
      jejuni and by a spot test that the growth of C. jejuni was reduced relative to
      control bacteria in the region of phage application. There may be two interesting
      applications of this effect. First, it may be possible to test phage PV22 as an
      antimicrobial agent to decrease C. jejuni colonization of the chicken intestine.
      Second, the phage could potentially be utilized for investigating biogenesis of
      C. jejuni flagella.

PMID- 16803632
TI  - Factors affecting left ventricular remodeling after valve replacement for aortic
      stenosis. An overview.
AB  - Although a small percentage of patients with critical aortic stenosis do not
      develop left ventricle hypertrophy, increased ventricular mass is widely observed
      in conditions of increased afterload. There is growing epidemiological evidence
      that hypertrophy is associated with excess cardiac mortality and morbidity not
      only in patients with arterial hypertension, but also in those undergoing aortic
      valve replacement. Valve replacement surgery relieves the aortic obstruction and
      prolongs the life of many patients, but favorable or adverse left ventricular
      remodeling is affected by a large number of factors whose specific roles are
      still a subject of debate. Age, gender, hemodynamic factors, prosthetic valve
      types, myocyte alterations, interstitial structures, blood pressure control and
      ethnicity can all influence the process of left ventricle mass regression, and
      myocardial metabolism and coronary artery circulation are also involved in the
      changes occurring after aortic valve replacement. The aim of this overview is to
      analyze these factors in the light of our experience, elucidate the important
      question of prosthesis-patient mismatch by considering the method of effective
      orifice area, and discuss surgical timings and techniques that can improve the
      management of patients with aortic valve stenosis and maximize the probability of
      mass regression.

PMID- 16803635
TI  - Study of thioglycosylation in ionic liquids.
AB  - A novel, green chemistry, glycosylation strategy was developed based upon the use
      of ionic liquids. Research studies demonstrated that thiomethyl glycosides could
      readily be activated with methyl trifluoromethane sulfonate, using 1-butyl-3
      methylimidazolium tetrafluoroborate as a solvent. This green chemistry
      glycosylation strategy provided disaccharides with typical yields averaging 75%.
      The ionic liquid solvent could be readily reused for five sequential
      glycosylation reactions with no impact on product yield.

PMID- 16803633
TI  - Heat shock protein expression in canine malignant mammary tumours.
AB  - BACKGROUND: Abnormal levels of Heat Shock Proteins (HSPs) have been observed in
      many human neoplasms including breast cancer and it has been demonstrated that
      they have both prognostic and therapeutic implications. In this study, we
      evaluated immunohistochemical expression of HSPs in normal and neoplastic canine
      mammary glands and confronted these results with overall survival (OS), in order
      to understand the role of HSPs in carcinogenesis and to establish their potential
      prognostic and/or therapeutic value. METHODS: Immunohistochemical expression of
      Hsp27, Hsp72, Hsp73 and Hsp90 was evaluated in 3 normal canine mammary glands and
      30 malignant mammary tumours (10 in situ carcinomas, 10 invasive carcinomas
      limited to local structures without identifiable invasion of blood or lymphatic
      vessels, 10 carcinomas with invasion of blood or lymphatic vessels and/or
      metastases to regional lymph nodes). A semi-quantitative method was used for the
      analysis of the results. RESULTS: Widespread constitutive expression of Hsp73 and
      Hsp90 was detected in normal tissue, Hsp72 appeared to be focally distributed and
      Hsp27 showed a negative to rare weak immunostaining. In mammary tumours, a
      significant increase in Hsp27 (P < 0.01), Hsp72 (P < 0.05) and Hsp90 (P < 0.01)
      expression was observed as well as a significant reduction in Hsp73 (P < 0.01)
      immunoreactivity compared to normal mammary gland tissue. Hsp27 demonstrated a
      strong positivity in infiltrating tumour cells and metaplastic squamous elements
      of invasive groups. High Hsp27 expression also appeared to be significantly
      correlated to a shorter OS (P = 0.00087). Intense immunolabelling of Hsp72 and
      Hsp73 was frequently detected in infiltrative or inflammatory tumour areas. Hsp90
      expression was high in all tumours and, like Hsp73, it also showed an intense
      positivity in lymphatic emboli. CONCLUSION: These results suggest that Hsp27,
      Hsp72 and Hsp90 are involved in canine mammary gland carcinogenesis. In addition,
      Hsp27 appears to be implicated in tumour invasiveness and its high
      immunodetection in invasive tumours is indicative of a poorer clinical outcome.

PMID- 16803634
TI  - Impact of hormonal therapy on the detection of promoter hypermethylation of the
      detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer.
AB  - BACKGROUND: In spite of excellent cure rates for prostate cancer patients with
      favorable tumor characteristics, patients with unfavorable characteristics after
      radical prostatectomy are still at a significantly increased risk of tumor
      progression. Early adjuvant hormonal therapy (AHT) has been shown to be of
      prognostic benefit in these patients. Unfortunately initiation and duration of
      early AHT in the individual patient is based on statistic data. PSA, as the
      standard prostate marker is neither able to reliably indicate minimal residual
      tumor disease in the early postoperative phase, nor can it be used for therapy
      monitoring due to the suppressive effect of hormonal therapy on PSA production.
      Promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene
      (GSTP1-HM) has been shown to be the most common DNA alteration of primary
      prostatic carcinoma which, when used as a marker, is supposed to be able to
      overcome some of the disadvantages of PSA. However until now information on the
      impact of hormonal therapy on the detection of GSTP1-HM is lacking. The purpose
      of our study was to assess the impact of endocrine therapy on the detection of
      GSTP1-HM by methylation-specific PCR (MSP) in prostate cancer. METHODS: Paraffin
      embedded tumor samples from the radical prostatectomy (RP) specimens from 15
      patients after hormonal therapy (HT) (mean 8 months) were assessed by MSP. In 8
      of the patients the GSTP-1 status of the tumors before HT was assessed on the
      corresponding initial diagnostic biopsies. RESULTS: Following HT MSP showed GSTP1
      HM in 13/15 of the RP specimens. In two patients analysis of the RP specimens
      failed to show GSTP1-HM. All initial tumor samples (8/8 biopsy specimens) showed
      GSTP1-HM, including both patients negative for GSTP1 HM in the corresponding RP
      specimen. CONCLUSION: In most cases hormonal therapy appears to not alter GSTP1
      HM detection. However the change from a positive to a negative GSTP1 HM status in
      a subset of the patients may point to an, at least partial androgen dependency.
      Further studies on a larger cohort of patients are necessary to assess its
      frequency and the exact hormonal interactions.

PMID- 16803636
TI  - Influence of simulated microgravity on the activation of the small GTPase Rho
      involved in cytoskeletal formation--molecular cloning and sequencing of bovine
      leukemia-associated guanine nucleotide exchange factor.
AB  - BACKGROUND: The irregular formation of cytoskeletal fibers in spaceflown
      experimental cells has been observed, but the disorganization process of fibers
      is still poorly understood. It is well known that the activation of the small
      GTPase Rho leads to actin stress fibers assembly. This study was performed to
      evaluate the effect of simulated microgravity on the activation of Rho that is
      involved in actin fiber remodeling in cells. RESULTS: Clinorotation influences
      actin fiber remodeling and its related signaling pathways that involve the small
      GTPase Rho. Actin stress fiber remodeling was significantly inhibited to a
      greater extent in cells cultured under clinorotation than in static cultured
      cells. From the gene and protein expression analyses, we found that the
      expression level of leukemia-associated Rho guanine nucleotide exchange factor
      (LARG), which activates Rho, was downregulated under clinorotation. Moreover, we
      identified the full-length LARG cDNA. The amount of GTP-bound RhoA, that is, the
      active form of RhoA, decreased under this condition. CONCLUSION: The activation
      of the small GTPase Rho was influenced by simulated microgravity generated by a
      three-dimensional (3D) clinostat. Furthermore, the full-length cDNA of bovine
      LARG, a member of the Rho guanine nucleotide exchange factor (GEF) family, was
      identified, and its gene expression was observed to be downregulated under
      clinorotation. This downregulation subsequently resulted in the repression of
      RhoA activation. These results indicated that the disorganization of the actin
      fibers was caused by the inhibition of Rho activation by 3D clinorotation.

PMID- 16803637
TI  - Effective NSAID treatment indicates that hyperprostaglandinism is affecting the
      clinical severity of childhood hypophosphatasia.
AB  - BACKGROUND: Hypophosphatasia (HP) is an inborn error of bone metabolism
      characterized by a genetic defect in the gene encoding the tissue-nonspecific
      alkaline phosphatase (TNSALP). There is a lack of knowledge as to how the
      variability and clinical severity of the HP phenotype (especially pain and
      walking impairment) are related to metabolic disturbances or impairments,
      subsequent to the molecular defect. METHODS: We analyzed the changes in clinical
      symptoms and the prostaglandin (PG) metabolism in response to treatment with non
      steroidal anti-inflammatory drugs (NSAIDs) in six children affected by childhood
      HP. In addition, by exposing HP fibroblasts to pyridoxal phosphate and/or calcium
      pyrophosphate in vitro, we analyzed whether the alterations in PG levels are
      sequelae related to the metabolic defect. RESULTS: Childhood HP patients, who
      often complain about pain in the lower limbs without evident fractures, have
      systemic hyperprostaglandinism. Symptomatic anti-inflammatory treatment with
      NSAIDs significantly improved pain-associated physical impairment. Calcium
      pyrophosphate, but not pyridoxal phosphate, induced cyclooxygenase-2 (COX-2) gene
      expression and PG production in HP and normal fibroblasts in vitro. CONCLUSION:
      Clinical features of childhood HP related to pain in the lower legs may be, at
      least in part, sequelae related to elevated PG levels, secondary to the primary
      metabolic defect. Consequently, NSAID treatment does improve the clinical
      features of childhood HP.

PMID- 16803640
TI  - Laboratory environments and rodents' behavioural needs: a review.
AB  - Laboratory housing conditions have significant physiological and psychological
      effects on rodents, raising both scientific and humane concerns. Published
      studies of rats, mice and other rodents were reviewed to document behavioural and
      psychological problems attributable to predominant laboratory housing conditions.
      Studies indicate that rats and mice value opportunities to take cover, build
      nests, explore, gain social contact, and exercise some control over their social
      milieu, and that the inability to satisfy these needs is physically and
      psychologically detrimental, leading to impaired brain development and
      behavioural anomalies (e.g. stereotypies). To the extent that space is a means to
      gain access to such resources, spatial confinement likely exacerbates these
      deficits. Adding environmental 'enrichments' to small cages reduces but does not
      eliminate these problems, and I argue that substantial changes in housing and
      husbandry conditions would be needed to further reduce them.

PMID- 16803639
TI  - Functional inhibition of NF-kappaB signal transduction in alphavbeta3 integrin
      expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant
      IkappaB gene.
AB  - In order to selectively block nuclear factor kappaB (NF-kappaB)-dependent signal
      transduction in angiogenic endothelial cells, we constructed an alphavbeta3
      integrin specific adenovirus encoding dominant negative IkappaB (dnIkappaB) as a
      therapeutic gene. By virtue of RGD modification of the PEGylated virus, the
      specificity of the cell entry pathway of adenovirus shifted from coxsacki
      adenovirus receptor dependent to alphavbeta3 integrin dependent entry. The
      therapeutic outcome of delivery of the transgene into endothelial cells was
      determined by analysis of cellular responsiveness to tumor necrosis factor (TNF)
      alpha. Using real time reverse transcription PCR, mRNA levels of the cell
      adhesion molecules E-selectin, vascular cell adhesion molecule (VCAM)-1 and
      intercellular adhesion molecule (ICAM)-1, the cytokines/growth factors IL-6, IL-8
      and vascular endothelial growth factor (VEGF)-A, and the receptor tyrosine kinase
      Tie-2 were assessed. Furthermore, levels of ICAM-1 protein were determined by
      flow cytometric analysis. RGD-targeted adenovirus delivered the dnIkappaB via
      alphavbeta3 to become functionally expressed, leading to complete abolishment of
      TNF-alpha-induced up-regulation of E-selectin, ICAM-1, VCAM-1, IL-6, IL-8, VEGF-A
      and Tie-2. The approach of targeted delivery of dnIkappaB into endothelial cells
      presented here can be employed for diseases such as rheumatoid arthritis and
      inflammatory bowel disease where activation of NF-kappaB activity should be
      locally restored to basal levels in the endothelium.

PMID- 16803641
TI  - The isolated perfused rat liver: standardization of a time-honoured model.
AB  - For many years, the isolated perfused rat liver (IPRL) model has been used to
      investigate the physiology and pathophysiology of the rat liver. This in vitro
      model provides the opportunity to assess cellular injury and liver function in an
      isolated setting. This review offers an update of recent developments regarding
      the IPRL set-up as well as the viability parameters that are used, with regards
      to liver preservation and ischaemia and reperfusion mechanisms.A review of the
      literature was performed into studies regarding liver preservation or liver
      ischaemia and reperfusion. An overview of the literature is given with particular
      emphasis on perfusate type and volume, reperfusion pressure, flow, temperature,
      duration of perfusion, oxygenation and on applicable viability parameters (liver
      damage and function). The choice of IPRL set-up depends on the question examined
      and on the parameters of interest. A standard technique is cannulation of the
      portal vein, bile duct and caval vein with pressure-controlled perfusion at 20 cm
      H2O (15 mmHg) to reach a perfusion flow of approximately 3 mL/min/g liver weight.
      The preferred perfusion solution is Krebs-Henseleit buffer, without albumin. The
      usual volume is 150-300 cm3, oxygenated to a pO2 of more than 500 mmHg. The
      temperature of the perfusate is maintained at 37 degrees C. Standardized markers
      should be used to allow comparison with other experiments.

PMID- 16803642
TI  - Microbiological monitoring of laboratory mice and biocontainment in individually
      ventilated cages: a field study.
AB  - Over recent years, the use of individually ventilated cage (IVC) rack systems in
      laboratory rodent facilities has increased. Since every cage in an IVC rack may
      be assumed to be a separate microbiological unit, comprehensive microbiological
      monitoring of animals kept in IVCs has become a challenging task, which may be
      addressed by the appropriate use of sentinel mice. Traditionally, these sentinels
      have been exposed to soiled bedding but more recently, the concept of exposure to
      exhaust air has been considered. The work reported here was aimed firstly at
      testing the efficiency of a sentinel-based microbiological monitoring programme
      under field conditions in a quarantine unit and in a multi-user unit with
      frequent imports of mouse colonies from various sources. Secondly, it was aimed
      at determining biocontainment of naturally infected mice kept in an IVC rack,
      which included breeding of the mice. Sentinels were exposed both to soiled
      bedding and to exhaust air. The mice which were used in the study carried
      prevalent infectious agents encountered in research animal facilities including
      mouse hepatitis virus (MHV), mouse parvovirus (MPV), intestinal flagellates and
      pinworms. Our data indicate that the sentinel-based health monitoring programme
      allowed rapid detection of MHV, intestinal flagellates and pinworms investigated
      by a combination of soiled bedding and exhaust air exposure. MHV was also
      detected by exposure to exhaust air only. The IVC rack used in this study
      provided biocontainment when infected mice were kept together with non-infected
      mice in separate cages in the same IVC rack.

PMID- 16803643
TI  - The impact of different blood sampling methods on laboratory rats under different
      types of anaesthesia.
AB  - Rats with implanted telemetry transponders were blood sampled by jugular
      puncture, periorbital puncture or tail vein puncture, or sampled by jugular
      puncture in carbon dioxide (CO2), isoflurane or without anaesthesia in a
      crossover design. Heart rate, blood pressure and body temperature were registered
      for three days after sampling. Initially blood pressure increased, but shortly
      after sampling it decreased, which led to increased heart rate. Sampling induced
      rapid fluctuations in body temperature, and an increase in body temperature.
      Generally, rats recovered from sampling within 2-3 h, except for rats sampled
      from the tail vein, which showed fluctuations in body temperature in excess of 30
      h after sampling. Increases in heart rate and blood pressure within the first
      hours after sampling indicated that periorbital puncture was the method that had
      the largest acute impact on the rats and that it might take an extra hour to
      recover from it. CO2 anaesthesia seemed unable to prevent the increase in blood
      pressure and the fluctuations in body temperature induced by blood sampling, and
      up to 10 h after sampling, the rats were still affected by CO2 anaesthesia. Rats
      anaesthetized with isoflurane showed lower increases in blood pressure after, and
      fewer fluctuations in body temperature during sampling, and the post-anaesthetic
      effects of isoflurane, if any, seemed to disappear immediately after sampling. It
      is, therefore, concluded that blood sampling in rats by jugular puncture seems to
      be the method from which rats most rapidly recover when compared with periorbital
      puncture and tail vein puncture, and that for anaesthesia, isoflurane is
      recommended in preference to CO2.

PMID- 16803644
TI  - Non-surgical alternatives to invasive procedures in mice.
AB  - We have developed and validated catheterization protocols in mice that allow for
      simultaneous infusion and sampling. A sampling catheter was inserted in the
      lateral vein of the tail, while the animals were infused either intravenously or
      intragastrically through a second catheter placed in the contralateral lateral
      vein or via an intragastric catheter, respectively. The applicability of these
      methods of infusion and blood sampling were validated by conducting urea kinetics
      utilizing stable isotopes. These non-surgical procedures are non-invasive,
      inexpensive, fast to perform and animals do not require a recovery period before
      their use.

PMID- 16803645
TI  - Low frequency of Helicobacter species in the stomachs of experimental rabbits.
AB  - The natural occurrence of established Helicobacter species was investigated in
      the stomachs of 65 laboratory rabbits, by means of polymerase chain reaction
      (PCR) (65/65) and histological analysis (51/65). The degree of inflammation in
      the different regions of the rabbits' stomach was evaluated on haematoxylin and
      eosin (HE)-stained histological slides. Four rabbits were found positive for
      Helicobacter species by PCR. Based on 16S ribosomal ribonucleic acid (rRNA)
      sequences, H. canadensis/H. pullorum organisms were identified in three animals.
      Bacteria were seen on merely one histological slide from one of these animals. H.
      felis was identified in one rabbit. Histological examination revealed no
      inflammation in the stomachs of 40 rabbits, while moderate gastric inflammation
      was seen in 11 animals, mainly in the antrum. In conclusion, the stomach of the
      laboratory rabbits included in the study was occasionally found positive for
      Helicobacter species, which were mostly identified as enterohepatic
      helicobacters, probably reflecting a mere passage of these bacteria through the
      stomach.

PMID- 16803646
TI  - Some aspects of rat femorotibial joint microanatomy as demonstrated by high
      resolution magnetic resonance imaging.
AB  - High-resolution magnetic resonance images (MRI) of the right femorotibial joint
      of normal Han:Wistar rats were acquired using a 4.7 Tesla magnet and a single
      turn solenoid radio frequency coil (built in-house). Some anatomical findings of
      the rat femorotibial joint, which have not been reported previously using MRI,
      are described. The separation of patellar ligament and crural fascia was feasible
      on MRI. This separation would not be seen on images of lower resolution and its
      presence on high-resolution images could be mistaken for artefact due to the
      magic angle effect. Band-like fibrous structures exist in the infra-patellar fat
      pad, which might be mistaken as ligaments within the femorotibial joint. On
      sagittal MRI a vessel was seen inserted on the central part of the caudal surface
      of the patellar ligament. Subcutaneous fascia/cutaneous muscles (panniculus
      carnosus) could also be demonstrated with MRI in the femorotibial joint area.

PMID- 16803647
TI  - The effect of different doses of cisplatin on the pharmacokinetic parameters of
      cefepime in mice.
AB  - The simulation of human serum levels is essential in animal models to extrapolate
      the experimental results to clinical practice. Administration of a nephrotoxic
      drug such as cisplatin can be used to cause renal dysfunction as an approach to
      mimic human serum levels of renally excreted drugs. We aimed to determine the
      dose of cisplatin that did not affect the survival rate of mice and to achieve
      human-like serum concentrations of cefepime. Different doses of cisplatin (0, 10,
      14, 18, 22 and 26 mg/kg) were given by intraperitoneal (i.p.) injection to mice
      three days prior to the i.p. administration of 80 mg/kg cefepime. With cisplatin
      doses of 18 and 22 mg/kg, the half-life of cefepime was significantly prolonged
      (P < 0.001) and all mice survived. The pretreatment with 26 mg/kg cisplatin
      significantly decreased survival (P = 0.001), but the half-life of cefepime was
      not significantly longer than of 18 mg/kg cisplatin. Serum levels of cefepime
      after the pretreatment with 18 mg/kg cisplatin were comparable to published human
      data. The administration of cisplatin appears to be a suitable method in mice for
      simulating human serum concentrations of renally excreted drugs.

PMID- 16803648
TI  - Postanaesthetic tracheal strictures in three rabbits.
AB  - Within an 11-day period, three rabbits were anaesthetized for neutering. All were
      endotracheally intubated with 12 cm long, 2.5 mm (inner diameter [ID])
      polyvinylchloride (PVC) tubes. All rabbits developed clinical signs of dyspnoea
      and upper respiratory tract obstruction, 17-21 days later. One rabbit was found
      dead; the other two were treated, but one was euthanized and one died. At
      necropsy examination, focal chronic inflammation and significant localized
      narrowing of the tracheal lumen was found in all cases. The affected sites
      corresponded to the position of the bevel of the endotracheal tube (ETT) during
      anaesthesia. Histopathology could not differentiate between a traumatic or
      chemical cause for the narrowing. Possible causes include trauma by the bevel of
      the ETT when turning the rabbit or preparing the surgical site or a chemical burn
      from incorrect disinfection or inadequate rinsing of the tubes. Iatrogenic
      tracheitis should be considered as a cause of dyspnoea, when clinical signs arise
      2-3 weeks after anaesthesia.

PMID- 16803649
TI  - Laboratory rearing conditions for improved growth of juvenile Helix aspersa
      Muller snails.
AB  - A laboratory rearing system in semi-controlled conditions is proposed to
      facilitate the behavioural rhythms of the edible snail (Helix aspersa) and to
      produce a high growth rate with low variability. The growth data were used to
      construct a model for weight estimation based on age. The animals' live weights
      showed low variability (<17%) and normal distribution. The best model for
      estimating weight from age is the logistic model, with a high corelation
      coefficient (>90%), and a high level of significance for the coefficient (P <
      0.0001).

PMID- 16803650
TI  - Closed cup vapor systems in percutaneous exposure studies: what is the dose?
AB  - Percutaneous vapor dosing studies have generally used saturated vapor
      concentration (SVC) measurements to estimate the exposure dose (Ct) of vapor
      produced from a volatile liquid within a closed system. The purpose of this study
      was to clarify whether the assumption was valid when translated to a biological
      system (pig skin) using sulfur mustard (SM) as a model skin penetrant. Three
      systems were evaluated, two containing skin and a control system (without skin).
      At set time points, samples from the headspace of each dosing system were
      extracted using a gas-tight syringe and analyzed by gas chromatography in
      conjunction with a flame-ionization detector. This demonstrated the rapid
      achievement of a constant vapor concentration within the biological and control
      systems and enabled a comparison with previously determined SVCs attained under
      ideal conditions. All three systems attained a constant vapor concentration
      within 2 min of exposure to SM. The control system reached an equilibrium vapor
      concentration of 1179 +/- 164 mg/m3, a value not significantly different from
      that derived from the SVC (1363 mg/m3). Because of absorption in the skin
      systems, SM vapor concentrations were significantly lower than that derived from
      the SVC and were dependent on the skin surface area within the dosing chamber
      (592 +/- 246 mg/m3 for a surface area of 10.15 cm2 and 740 +/- 224 mg/m3 for a
      surface area of 2.54 cm2). The assumption that SVC gives an acceptable measure of
      the Ct was shown to be valid by comparison with sulfur mustard recovered from the
      skin.

PMID- 16803651
TI  - Application of two-dimensional gas chromatography with electron capture chemical
      ionization mass spectrometry to the detection of 11-nor-Delta9
      tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in hair.
AB  - The proposed federal regulations for the detection in hair of 11-nor-Delta(9)
      tetrahydrocannabinol-9-carboxylic acid (THC-COOH), a metabolite of marijuana,
      require a confirmatory detection level of 0.05 pg/mg. At present, the only way to
      achieve this on a routine basis has been with the use gas chromatography with
      tandem mass spectrometry (GC-MS-MS) technology. Tandem MS is an expensive
      approach and dissuades laboratories from attempting to enter the hair-testing
      market. A procedure for the determination of THC-COOH in hair using two
      dimensional gas chromatography (GC x GC) coupled to mass spectrometry (GC-GC-MS)
      is described for the first time. The method makes use of several small
      improvements in the extraction, GC, and MS procedures to allow the required
      sensitivity to be achieved. The results of this approach demonstrate detection of
      THC-COOH in hair at a concentration level of 0.05 pg/mg with both a target
      quantitation ion and a unique confirming qualifier ion, using a single-quadrupole
      mass selective detector. These two ions and the enhanced separation of the GC-GC
      provide a high degree of confidence in the determinations. The method has been
      successfully applied to the detection of THC-COOH in hair specimens from known
      marijuana users, and it reaches the levels currently proposed in the Federal
      Register.

PMID- 16803652
TI  - Quantitation of cotinine in nonsmoker saliva using chip-based nanoelectrospray
      tandem mass spectrometry.
AB  - A new analytical procedure was developed for the quantitation of nonsmoker
      salivary cotinine. Small volumes of saliva were diluted with water, fortified
      with cotinine-d3 (internal standard), then passed through small extraction
      columns. The analyte and internal standard were eluted with 0.1% (v/v) acetic
      acid/acetonitrile. Aliquots of each extract were analyzed directly, without
      chromatographic separation, using chip-based (NanoMate) nanospray tandem mass
      spectrometry. The calculated detection limit was 0.49 ng cotinine/mL saliva. This
      method was used to quantify salivary cotinine collected from nonsmoking human
      subjects living in one of three environmental tobacco smoke (ETS) exposure
      categories or "cells": 1. smoking home/smoking workplace; 2. smoking
      home/nonsmoking workplace; and 3. nonsmoking home/smoking workplace. Samples were
      collected during five sequential days, including Saturday, as part of a larger
      study to evaluate potential variability in exposure to ETS. Salivary cotinine
      measurements were made for the purpose of excluding misclassified smokers and for
      comparison with known levels of exposure to airborne nicotine in each exposure
      category. The concentrations observed were consistent with those reported from
      other large studies reported elsewhere. A non-parametric statistical test was
      applied to the data within each cell. No statistically significant differences
      were found between the mean cotinine concentrations collected on a weekday as
      compared to those collected on a weekend day. When the non-parametric test was
      applied to the three cells, a statistically significant difference was observed
      between cell 1 compared to cells 2 and 3. The salivary cotinine concentrations
      were thus statistically invariant over a five-day exposure period, and they were
      greatest under the conditions of smoking home and smoking workplace.

PMID- 16803653
TI  - Determination of three carcinogenic aromatic amines in urine of smokers and
      nonsmokers.
AB  - Aromatic amines (arylamines) such as o-toluidine, 2-aminonaphthalene, and 4
      aminobiphenyl occur in the environment and are constituents of tobacco smoke.
      Human exposure to these aromatic amines has long been associated with an elevated
      risk of bladder cancer. A validated, specific, and sensitive method for measuring
      o-toluidine, 2-aminonaphthalene, and 4-aminobiphenyl in cigarette smokers and
      nonsmokers was developed. The method uses acid hydrolysis of the arylamine
      conjugates in urine, extraction with n-hexane, derivatization with
      pentafluoropropionic anhydride, and subsequent analysis with gas chromatography
      combined with mass spectrometry using negative ion chemical ionization. The
      limits of detection were 4 ng/L for o-toluidine and 1 ng/L for 2-aminonaphthalene
      and 4-aminobiphenyl. Smokers (N = 10) excreted significantly higher amounts of o
      toluidine (204 versus 104 ng/24 h), 2-aminonaphthalene (20.8 versus 10.7 ng/24
      h), and 4-aminobiphenyl (15.3 versus 9.6 ng/24 h) than nonsmokers (N = 10).
      Urinary arylamine excretion in smokers was associated with the extent of smoking
      as assessed by daily cigarette consumption, urinary excretion of nicotine
      equivalents (nicotine plus its five major metabolites), cotinine in saliva, and
      carbon monoxide in exhaled breath. All nonsmokers investigated had quantifiable
      amounts of o-toluidine, 2-aminonaphthalene, and 4-aminobiphenyl in their urine,
      confirming that other environmental sources of exposure to these compounds also
      occur. In conclusion, the analytical method is suitable for measuring short-term
      exposure to arylamines in urine of non-occupationally exposed smokers and
      nonsmokers.

PMID- 16803654
TI  - More reliable brain death diagnosis with chromatographic analysis of midazolam,
      diazepam, thiopentone, and active metabolites.
AB  - Brain death diagnosis may be confounded by centrally acting drugs. The certainty
      of brain death diagnosis can be enhanced by demonstrating that the concentrations
      of such drugs are well below the therapeutic range. A combined high-performance
      liquid chromatography-based method was developed for the benzodiazepines
      midazolam, 1-hydroxymidazolam, 1-hydroxymidazolam glucuronide, diazepam, and
      nordiazepam and for the barbiturates thiopentone and pentobarbitone in serum or
      plasma of critically ill patients. The lower limits of detection of the assays
      for benzodiazepines and barbiturates were 2.5 ng/mL and 0.05 microg/mL. The lower
      limits of the working ranges of these assays were set at 25 ng/mL and 0.5
      microg/mL, respectively, and are below the lowest pharmacologically active plasma
      concentrations of these drugs. Intra- and interday coefficients of variations
      were less than 2.5% and 11.0% throughout, as determined with six replicates (n =
      6). These assays were accurate in that the relative difference between actually
      measured and expected concentration never exceeded 12%. Utilization of these
      assays will render the diagnosis of brain death more reliable.

PMID- 16803655
TI  - Hydromorphone-related fatalities in ontario.
AB  - The interpretation of drug intoxication in death investigations is based on the
      available published literature. In the case of hydromorphone, the literature is
      limited. This report serves to facilitate the evaluation of cases where
      hydromorphone may be implicated in a fatality through the examination of 251
      hydromorphone-positive cases in the province of Ontario from 1985 to 2003. Thirty
      three of these cases were selected for review in greater detail. In four cases in
      which hydromorphone was the sole drug detected and death was attributed to
      hydromorphone toxicity, concentrations ranged from 77 to 2684 ng/mL.
      Hydromorphone concentrations ranged from 21 to 441 ng/mL in 28 cases in which at
      least one other drug was detected. In five deaths attributed to natural causes,
      blood hydromorphone concentrations ranged from 75 to 423 ng/mL. The results of
      this study emphasize the importance of case specific information. Fatalities due
      to hydromorphone occurred at 51 ng/mL and greater; however, tolerant users of
      this drug, as seen in the deaths attributed to natural causes, may achieve
      incidental concentrations that would otherwise be considered fatal. Hydromorphone
      was detected and quantitated using gas chromatography-mass spectrometry.

PMID- 16803656
TI  - A novel LC-ESI-MS-MS method for sensitive quantification of colchicine in human
      plasma: application to two case reports.
AB  - A novel method based upon liquid chromatography coupled to ion trap mass
      spectrometry (MS) detection with electrospray ionization interface has been
      developed for the identification and quantification of colchicine in plasma or
      whole blood. Colchicine was isolated from plasma using a liquid-liquid extraction
      with dichloromethane at pH 8.0 and embutramide as an internal standard, with
      satisfactory extraction recoveries. Solutes were separated on a 3-microm C18
      Uptisphere (Interchim) column (150 x 2.0-mm i.d.) using acetonitrile/2 mM NH4COOH
      pH 3.8 buffer (50:50, v/v) as the mobile phase with a flow-rate of 200
      microL/min. Data were collected either in full-scan MS mode at m/z 100-450 or in
      full-scan MS-MS mode, selecting the ion m/z 400.1 for colchicine and m/z 294.1
      for embutramide. The most intense daughter ion of colchicine (m/z 358.1) and
      embutramide (m/z 207.9) were used for quantification. Retention times were 2.40
      and 4.25 min for colchicine and embutramide, respectively. Calibration curves
      were linear in the 0.50-50 ng/mL range. The limits of detection and
      quantification were 0.05 ng/mL and 0.50 ng/mL, respectively. The intra- and
      interassay precisions were < 14%, and the intra- and interassay accuracies were
      in the 97-105.8% range at either 2 or 20 ng/mL. A fatal case of colchicine self
      poisoning with a lethal blood concentration of 60 ng/mL and nonfatal case with a
      plasma sample collected very late (at least 36 h after the ingestion) are
      presented. The described method enables the unambiguous identification and
      quantification of colchicine with a very good sensitivity, using only 1 mL of
      sample.

PMID- 16803657
TI  - An unusual autoerotic fatality associated with chloroform inhalation.
AB  - We report the death of a young male attributed to chloroform poisoning during
      autoerotic asphyxia. He was found lying on the floor of his apartment, prone on a
      piece of foam and a towel. His eyes were bound with a towel, his lower face and
      nose were almost entirely covered with duct tape surrounding a rubber hose in his
      mouth. The other end of the hose was loosely sitting inside an open bottle which
      was in a box beside him. He was bound-up by an intricate system of ropes,
      handles, and rods, ending with a noose around his neck. Toxicology testing
      indicated chloroform concentrations of 18.1 mg/L in femoral blood and 1.5 mg/L in
      urine. Chloroform was measured by headspace gas chromatography with flame
      ionization detection using 1,1,1-trichloroethane as the internal standard. The
      cause of death was recorded as "chloroform toxicity" with "autoerotic asphyxia"
      as a contributing factor, and the manner of death was "accidental".

PMID- 16803658
TI  - Two deaths attributed to the use of 2,4-dinitrophenol.
AB  - We report the cases of two individuals, one in Tacoma, WA, and the second in San
      Diego, CA, whose deaths were attributed to ingestion of 2,4-dinitrophenol (2,4
      DNP). 2,4-DNP has historically been used as a herbicide and fungicide. By
      uncoupling mitochondrial oxidative phosphorylation, the drug causes a marked
      increase in fat metabolism that has led to its use to aid weight loss. Both cases
      reported here involved its use for this purpose. Features common to both cases
      included markedly elevated body temperature, rapid pulse and respiration, yellow
      coloring of the viscera at autopsy, history of use of weight loss or body
      building supplements, and presence of a yellow powder at the decedent's
      residence. Because of its acidic nature, the drug is not detected in the basic
      drug fraction of most analytical protocols, but it is recovered in the
      acid/neutral fraction of biological extracts and can be measured by high
      performance liquid chromatography or gas chromatography-mass spectrometry. The
      concentration of 2,4-DNP in the admission blood samples of the two deaths
      reported here were 36.1 and 28 mg/L, respectively. Death in both cases was
      attributed to 2,4-DNP toxicity. Review of information available on the internet
      suggests that, although banned, 2,4-DNP is still illicitly promoted for weight
      loss.

PMID- 16803659
TI  - Urinary excretion of morphine and codeine following the administration of single
      and multiple doses of opium preparations prescribed in Taiwan as "brown mixture".
AB  - Parallel to the "poppy-seed defense" strategy commonly reported in the United
      States, donors of urine samples tested positive for opiates in Taiwan often
      claimed the consumption of Brown Mixture (BM) as the source of the observed
      morphine and codeine. Because BM contains opium powder (10.0-10.5% morphine),
      opium tincture (0.9-1.1% morphine), or camphorated opium tincture (0.045-0.055%
      morphine) and is a popular remedy, and heroin use is considered a serious
      criminal act, the claim of BM use has to be adequately addressed. In this study,
      BM from seven different manufacturers (5 tablets and 2 solutions) and urine
      samples from alleged heroin users and volunteers with various ingestion patterns
      and were analyzed for their morphine and codeine contents. The analytical
      procedure included hydrolysis, trimethylsilylation, and gas chromatography-mass
      spectrometry analysis. The contents of morphine and codeine in the tablets were
      found to be very consistent, but with significant differences in the two BM
      solutions. Morphine concentrations found in urine specimens collected from
      volunteers ingesting BM tablets (or solutions) were always < 4000 ng/mL. The
      following morphine-to-codeine ([M]/[C]) ratios were observed for urine specimens
      with morphine concentration > or = 300 ng/mL: (A) < 3.0 for volunteers ingesting
      BM solution and (B) > 3.0 (mostly > 5.0) for volunteers ingesting BM tablets and
      alleged heroin users. It appeared that (A) BM ingestion (tablet or solution) was
      unlikely to result in a morphine concentration > 4000 ng/mL; and (B) [M]/[C]
      ratio might not be an effective parameter to differentiate heroin use from BM
      tablet ingestion.

PMID- 16803660
TI  - High-performance liquid chromatographic-mass spectrometric determination of
      methamphetamine and amphetamine enantiomers, desmethylselegiline and selegiline,
      in hair samples of long-term methamphetamine abusers or selegiline users.
AB  - We devised a highly sensitive method for simultaneously determining
      methamphetamine (MA) and amphetamine (AP) enantiomers, desmethylselegiline (DMSG)
      and selegiline (SG), in human hair using a derivatization technique and high
      performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC
      ESI-MS). MA and AP enantiomers and DMSG were effectively converted to
      trifluoroacetic acid (TFA) derivatives, and the sensitivity of MA and DMSG
      increased five times over compared with that of free bases. The TFA derivatives
      of each compound were stable within one week in a stock solution of methanol or
      for 24 h in the HPLC mobile phase (mixture of methanol and ammonium formate
      buffer). Each compound was well separated, and calibration curves were linear in
      the concentration range 0.04-40 ng/mg for MA enantiomers, SG and DMSG, and 0.2-40
      ng/mg for AP enantiomers. The accuracy and precision of the method were
      evaluated, and relative standard deviations were within 7%. Our method was
      successfully applied to hair samples obtained from long-term MA abusers and SG
      users. (+)-MA and (+)-AP were detected from three MA abusers at concentrations of
      0.79-20.85 and 0.04-3.30 ng/mg, respectively. On the other hand, (-)-MA, (-)-AP,
      DMSG, and SG were detected in three SG users at concentrations of 2.48-9.05, 0.72
      3.10, 0.12-0.59, and 0-0.04 ng/mg, respectively. Based on our obtained data,
      discrimination of MA abusers from SG users was considered to be possible by
      comparing optical isomers of MA and AP, the existence of DMSG and/or SG, and the
      concentration ratio of AP to MA in hair samples.

PMID- 16803661
TI  - Quantitative analysis of buprenorphine and norbuprenorphine in urine using liquid
      chromatography tandem mass spectrometry.
AB  - Buprenorphine is an opioid analgesic drug that is used as an alternative to
      methadone to treat heroin addiction. Established methods for the analysis of
      buprenorphine and its metabolites in urine such as gas chromatography-mass
      spectrometry (GC-MS) involve complicated sample extraction procedures. The aim of
      the present study was to develop a sensitive yet straightforward method for the
      simultaneous analysis of buprenorphine and norbuprenorphine in urine using liquid
      chromatography-MS-MS. The method comprised an enzymatic hydrolysis using Patella
      vulgata b-glucuronidase, followed by centrifugation and direct analysis of the
      supernatant. The limits of detection and quantitation were < 1 microg/L for
      buprenorphine and < 1 and 4 microg/L, respectively, for norbuprenorphine. Assay
      coefficients of variation (CVs) were < 15%, with the exception of concentrations
      close to the limit of quantitation, where CVs were below 20%. In direct
      comparison with an established GC-MS protocol, the method showed minimal negative
      bias (8.7% for buprenorphine and 1.8% for norbuprenorphine) and was less
      susceptible to sample carryover. The extent of conjugation in unhydrolyzed urine
      was investigated and found to be highly variable, with proportions of
      unconjugated buprenorphine and norbuprenorphine of 6.4% [range 0% to 67%;
      standard deviation (SD) 9.7%] and 34% (range 0% to 100%; SD 23.8%), respectively.

PMID- 16803662
TI  - Quantification of metaxalone in human plasma by liquid chromatography coupled to
      tandem mass spectrometry.
AB  - A simple, rapid, sensitive, and selective liquid chromatography-tandem mass
      spectrometry (MS) method was developed and validated for the quantification of
      metaxalone, a skeletal muscle relaxant, in human plasma using galantamine as
      internal standard (IS). Following liquid-liquid extraction, the analytes were
      separated using an isocratic mobile phase on a reverse phase C18 column and
      analyzed by MS in the multiple reaction monitoring mode using the respective
      [M+H]+ ions, m/z 222/161 for metaxalone and m/z 288/213 for the IS. The assay
      exhibited a linear dynamic range of 50-5000 microg/L for metaxalone in human
      plasma. The lower limit of quantification was 50 microg/L with a relative
      standard deviation of less than 10%. Acceptable precision and accuracy were
      obtained for concentrations over the standard curve range. A run time of 2.5 min
      for each sample made it possible to analyze more than 400 human plasma samples
      per day. The validated method has been successfully used to analyze human plasma
      samples for application in pharmacokinetic, bioavailability, or bioequivalence
      studies.

PMID- 16803663
TI  - Gas chromatography analysis of urinary alkoxyacetic acids as biomarkers of
      exposure to aliphatic alkyl ethers.
AB  - Analysis of alkoxyacetic acids has received considerable research interest in
      toxicology because these compounds have been reported as metabolites and
      biomarkers of exposure to widely used industrial chemicals such as alkyl
      substituted ethylene glycols and other aliphatic ethers. This paper describes an
      improved method for the determination of methoxyacetic acid (MAA), ethoxyacetic
      acid (EAA), and butoxyacetic acid (BAA) in rat urine. Solid-phase extraction with
      Bakerbond(T) C18 bonded silica cartridges was successfully employed to isolate
      the acids from rat urine. The acids were then converted to methyl esters with
      diazomethane derivatization and analyzed using a gas chromatograph (GC) equipped
      with a mass spectrometry (MS) and a GC with flame ionization detector (FID).
      Employing GC-MS under selected ion monitoring detection, the lowest detection
      concentrations for MAA, EAA, and BAA were determined to be from 2 to 4 ng/mL
      urine in 1 mL of sample size. This method is 5 to 10 times more sensitive than
      that using GC-FID. The method described here is superior to the existing ones
      reported in the literature in that it employs an easy sample treatment procedure
      and gives much higher recoveries, making it suitable for routine assays. The
      utility of this new method was demonstrated in a toxicology study of aliphatic
      alkyl ethers.

PMID- 16803664
TI  - High-performance liquid chromatography method for urinary trans,trans-muconic
      acid. Application to environmental exposure to benzene.
AB  - This report describes a specific and precise high-performance liquid
      chromatography (HPLC) method for the quantification of trans,trans-muconic acid
      in human urine. The procedure involved a highly efficient Bond-Elut SAX
      extraction with 20% acetic acid elution. The HPLC analysis used a sodium
      acetate/methanol mobile phase with a C18 reverse phase column and UV detection at
      265 nm. The recovery, precision, linearity, and limits of detection and
      quantification of the method were determined. Mean absolute recoveries were
      between 97% and 115%. The calibration curve showed a correlation coefficient of
      0.9955 and the limit of detection was determined to be 10.8 microg/L. The method
      is suitable for evaluation of occupational and environmental benzene exposure in
      humans. The study of urinary trans,trans-muconic acid of two populations of
      children to evaluate environmental benzene exposure is presented.

PMID- 16803665
TI  - The detection of Delta9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Delta9
      tetrahydrocannabinol (THCA) in whole blood using two-dimensional gas
      chromatography and EI-mass spectrometry.
AB  - A method is described for the simultaneous analysis of Delta(9)
      tetrahydrocannabinol (THC) and its carboxylic acid metabolite, 11-nor-9-carboxy
      Delta(9)-tetrahydrocannabinol (THCA) as their trimethylsiyl derivatives using 2
      dimensional chromatography and electron ionization-mass spectrometric detection.
      The addition of a Deans switch to a standard GC oven allows the use of two
      chromatographic columns of differing stationary phase to greatly reduce matrix
      interference. The analytes are extracted from 1 mL of whole blood by first
      precipitating the blood proteins with the addition of acetonitrile followed by
      solid-phase extraction. The limit of quantitation for both THC and THCA was
      determined to be 1.0 ng/mL. The between-run precision at 1.0 ng/mL (N = 30) was
      7.7% and 7.4% for THC and THCA, respectively. The method is linear from 1 to 100
      ng/mL.

PMID- 16803666
TI  - Comparison of the various opiate alkaloid contaminants and their metabolites
      found in illicit heroin with 6-monoacetyl morphine as indicators of heroin
      ingestion.
AB  - In this study the use of the various opiate alkaloid contaminants as potential
      markers for illicit heroin ingestion were investigated. Urine samples (n = 227)
      taken from prisoners for routine drug screen, which were positive for opiates by
      immunoassay screening, were analyzed for contaminants in illicit heroin. A
      previously described method was used for the analysis; urines were extracted
      using mixed-mode solid-phase extraction; the extracts were derivatized using N
      methyl-bistrifluoroacetamide and N-methyl-N
      trimethylsilyltrifluoroactamide/trimethylchlorosilane. The derivatized extracts
      were subjected to electron impact gas chromatography-mass spectrometry. The
      extracts were injected in full scan mode followed by selected ion monitoring mode
      for target opiate alkaloids found as contaminants in illicit heroin. The opiate
      alkaloids and their metabolites specifically targeted included meconine,
      desmethylmeconine, hydrocotarnine, acetylcodeine, codeine, morphine, 6
      monacetylmorphine (6-mam), papaverine, hydroxypapaverine, and
      dihydroxypapaverine. Of the 227 samples positive for opiates by immunoassay,
      using a cut-off of 300 ng/mL, 199 were confirmed positive for morphine and using
      a cut-off of 10 ng/mL, 28 were confirmed positive for 6-mam. Using the screening
      method described in the study, the following numbers of positives were found: 199
      for morphine, 103 for codeine, 5 for meconine, 46 for desmethylmeconine, 18 for 6
      mam, 136 for hydroxypapaverine, and 139 for dihydroxypapaverine. Acetylcodeine,
      hydrocotarnine, and papaverine were not detected in any of the samples. The
      results of this study show that analysis for papaverine metabolites is more
      sensitive than 6-mam as a way of demonstrating illicit heroin use.

PMID- 16803667
TI  - Assay of Delta9-tetrahydrocannabinol (THC) in oral fluid-evaluation of the
      OraSure oral specimen collection device.
AB  - Oral fluid is considered to be an alternative to urine testing for the detection
      of acute ingestion of drugs. The OraSure Intercept DOA Oral Specimen Collection
      Device (OSCD) has been used in studies for the quantitation of Delta9
      tetrahydrocannabinol (THC), but concerns have been raised. In the present study,
      we investigated whether the volume of oral fluid can be determined and how much
      THC remains adsorbed on the device. It was found that THC is markedly adsorbed
      onto the absorptive pad. The recovery using the standard elution procedure was
      only 37.8 +/- 9.4% for 10 ng/mL and 55.6 +/- 1.0% for 100 ng/mL of THC in oral
      fluid (n = 5 each). With an additional methanol wash, a further 25% could be
      eluted. Therefore, a modification of the procedure was evaluated, consisting of
      the addition of 2 mL of methanol to the elution buffer. THC could be completely
      recovered over a range of concentrations (1 to 1000 ng/mL). For the determination
      of the amount of oral fluid absorbed, a gravimetric approach was evaluated as the
      weights of the devices vary only by 0.6% relative standard deviation. After
      application of 0.5 mL oral fluid to pads and evaluation of the weight
      differences, the applied amount could be estimated with a precision of 7.5% (n =
      8) and an accuracy of 6.1%. From these results it can be concluded that the
      OraSure OSCD is useful to collect oral fluid for reliable quantitative THC assay
      applying a modified elution procedure and gravimetric determination of the amount
      of oral fluid.

PMID- 16803668
TI  - Distribution of orally ingested hydrochloric acid in the thoracoabdominal cavity
      after death.
AB  - The authors encountered a case of hydrochloric acid (HCl) poisoning, thought to
      be caused by oral ingestion of concentrated HCl. Coagulation of the surface of
      the tongue and the mucosa of the pharynx, esophagus, and stomach were observed at
      forensic autopsy. An overabundance of Cl- was found in the gastric contents,
      corresponding to 8.19 mL of concentrated HCl. This was suggested to be a lethal
      oral dose of concentrated HCl, and the cause of death was determined to be HCl
      poisoning. Measuring the pH and concentrations of various ions in body fluids and
      contents of the alimentary tract enabled postmortem diffusion of HCl to be
      determined.

PMID- 16803669
TI  - Acute bromadiolone intoxication.
AB  - A 55-year-old man came to the hospital with a bleeding wound on his tongue. The
      coating of his tongue was green, and his sputum was red. Because an increased
      international normalized ratio-value was measured, a blood sample was sent to our
      laboratory with the suspicion of coumarin intoxication. Liquid chromatography
      electrospray ionization-mass spectrometry (LC-ESI-MS) analysis confirmed the
      poisoning was by bromadiolone, with its maximum serum concentration at 440
      microg/L. The analysis of further samples resulted in a calculated elimination
      half-life of 140 h. The analytical method described was developed for the
      determination and quantitation of bromadialone using LC-MS. This method is
      suitable for the simultaneous identification and quantitation of 10 indirect
      anticoagulants in human serum, which include five superwarfarins (brodifacoum,
      bromadiolone, difenacoum, difethialone, and flocoumafen) as rodenticides licenced
      in Germany and five other vitamin K antagonists (acenocoumarol, coumatetralyl,
      coumachlor, phenprocoumon, and warfarin). The method is based on an acidic (pH
      4.2) liquid-liquid extraction followed by LC-ESI-MS analysis. Analytical
      separation was carried out using an Atlantis C18 column (2.1 x 20 mm, 3 microm).
      The mobile phase consisted of methanol/0.1% formic acid; the flow rate was 0.6
      mL/min, and the time needed for analysis was 5 min. The lower limit of
      quantitation was 5 microg/L (signal-to-noise > 10).

PMID- 16803670
TI  - Tissue distribution of quetiapine in 20 cases in Virginia.
AB  - Quetiapine fumarate (Seroquel) is a dibenzothiazepine psychotropic agent that was
      introduced in 1997 for treating psychoses. Quetiapine is being found with
      increasing frequency in postmortem cases in Virginia. We report the postmortem
      results and histories of 20 quetiapine cases from the Office of the Chief Medical
      Examiner in Virginia covering the period 1999 through 2004. Quetiapine was
      extracted from blood using a basic drug solid-phase extraction (SPE) and
      identified by full scan electron impact gas chromatography-mass spectrometry (GC
      MS). Quetiapine quantification was accomplished by forming the trimethylsilyl
      derivative with bis(trimethylsilyl)trifluoracetamide/trimethylchlorosilane and
      using selected ion monitoring GC-MS. The quetiapine trimethylsilyl derivative
      ions acquired were m/z 210, 239, and 322. Methapyrilene was the internal
      standard, and ions m/z 97 and 58 were monitored. The method was linear from 0.1
      to 5.0 mg/L with a limit of quantitation of 0.1 mg/L. The quetiapine mean and
      range of concentrations found in each tissue are as follows: peripheral blood,
      7.7 mg/L (0.14-37 mg/L, n = 17); heart blood, 23.63 mg/L (0.53-76 mg/L, n = 4);
      liver, 91 mg/Kg (1.1-510 mg/Kg, n = 19); bile, 44 mg/L (6.0-96 mg/L, n = 4);
      urine, 15 mg/L (1.9-37 mg/L, n = 8); gastric, 897 mg total (3.5-3960 mg, n = 7);
      and vitreous, 1.4 mg/L (0.2-3.2 mg/L, n = 5). The average of all blood
      concentrations in 18 cases in which quetiapine contributed to the cause of death
      was 7.95 mg/L (0.4-76 mg/L). The manner of death in 13 of those cases was
      suicide, two were undetermined, and three were accidents. In two cases in which
      quetiapine was an incidental finding, the blood concentrations were 0.14 and 1.0
      mg/L. Quetiapine and other toxicological findings are presented with the cause
      and manner of death to assist in interpreting future quetiapine findings in
      postmortem samples.

PMID- 16803671
TI  - Granulocyte colony stimulating factor for mucositis during post-operative
      radiotherapy.

PMID- 16803672
TI  - Gene expression profiling in cervical cancer: state of the art and future
      directions.

PMID- 16803673
TI  - Predicting outcomes after percutaneous ethanol injection for small hepatocellular
      cancer.

PMID- 16803674
TI  - The links between obesity, leptin, and prostate cancer.

PMID- 16803675
TI  - Double-blind, placebo-controlled, randomized trial of granulocyte-colony
      stimulating factor during postoperative radiotherapy for squamous head and neck
      cancer.
AB  - To evaluate the ability of granulocyte-stimulating factor to decrease mucositis
      during postoperative radiotherapy for stage II-IV squamous head and neck cancer
      in a randomized, double-blind, placebo-controlled trial. METHODS: After
      undergoing complete resection, patients were randomized to receive granulocyte
      colony stimulating factor or placebo by daily subcutaneous injection during
      radiotherapy (63 Gy, 1.8 Gy/day). Patients undergoing prior radiotherapy or
      chemotherapy were excluded from the study. The primary outcome was the need for
      percutaneous endoscopic gastrostomy placement. Severity of mucositis was a
      secondary outcome. RESULTS: Forty-one patients were enrolled (132 planned). The
      study closed after slow accrual. Patient characteristics were as follows
      (granulocyte-colony stimulating factor vs placebo): median age, 59 versus 54
      years; pT4, 16% versus 23%; pN2/3, 68% versus 59%; stage IV, 79% versus 68%.
      Forty patients were evaluable for planned outcomes. Patients in the granulocyte
      colony stimulating factor arm showed trends toward lower rates of percutaneous
      endoscopic gastrostomy placement (0% vs 14%, P = 0.2) and severity of mucositis
      (P = 0.13), and had shorter mean radiotherapy duration (48.4 +/- 4.32 days vs
      51.6 +/- 1.84 days, P = 0.005). Overall survival was significantly greater in the
      granulocyte-colony stimulating factor arm (hazard ratio, 0.37; P = 0.037).
      DISCUSSION: Granulocyte-colony stimulating factor during radiotherapy was
      feasible and led to significantly shorter radiotherapy duration and trends toward
      less percutaneous endoscopic gastrostomy placement and mucositis. The
      unanticipated improvement in survival outcomes warrants further hypothesis-driven
      investigation and validation.

PMID- 16803676
TI  - Gene expression pattern associated with radiotherapy sensitivity in cervical
      cancer.
AB  - The objective of the present preliminary study was to determine if a difference
      in the pattern of gene expression exists between tumors that were subsequently
      found to be sensitive to radiotherapy and tumors found to be resistant to
      radiotherapy. PATIENTS AND METHODS: A total of 16 patients with invasive squamous
      cell carcinoma of the uterine cervix were included in this study. All patients
      were treated with standardized radiotherapy alone. Ten of the tumors were
      clinically radiosensitive and six were radioresistant. Total RNA, extracted from
      tumor specimens obtained prior to treatment, was hybridized onto an
      oligonucleotide microarray with probe sets complementary to over 20,000
      transcripts. The genes were first subjected to a statistical filter to identify
      genes with statistically significant differential expression levels between those
      that were radiosensitive and those that were radioresistant. A back-propagation
      neural network was then constructed to model the differences so that patterns
      could be easily identified. RESULTS: Although a number of genes were found to
      express differentially between radiosensitive and radioresistant tumors; the 10
      most discriminating genes were used to construct the model. Using the expressions
      from these 10 genes, we found that neural networks constructed from random
      subsets of the whole data were capable of predicting radiotherapy responses in
      the remaining subset, which appears stable within the dataset. DISCUSSION: This
      study shows that such an approach has the potential to differentiate tumor
      radiosensitivity, although confirmation of such a pattern using other larger
      independent datasets is necessary before firm conclusions can be drawn.

PMID- 16803677
TI  - Remission, relapse, and metastasis/death of small hepatocellular carcinoma
      treated with percutaneous ethanol injection.
AB  - PURPOSE: This study aimed to quantify the full clinical courses characterized by
      alternating transitions between remission and relapses for small hepatocellular
      carcinomas treated by percutaneous ethanol injection, and to ascertain the
      significant predictors for the remission, relapse, and finally to metastasis or
      death. PATIENTS AND METHODS: A three-state Markov process was used to depict full
      clinical course. A total of 108 patients who underwent nonsurgical therapy as the
      first choice of treatment were derived from consecutive clinical series of
      patients registered in one medical center renowned for their use of percutaneous
      ethanol injection. RESULTS: We found that approximately 57.19% (95% confidence
      interval [CI]: 39.82%, 74.56%) patients were promptly responsive to initial
      treatment, whereas 43.81% had delayed response or were resistant to treatment.
      The rate of relapse (per month) was higher than the rate of remission (19.20%
      [95% CI: 15.36%, 23.04%] vs. 13.82% [95% CI: 10.72%, 16.93%]). The results from
      the multivariate analysis indicate that the significant predictors for the full
      clinical courses are total bilirubin, alpha-fetoprotein, prothrombin time,
      globulin, tumor morphology, and alkaline phosphatase. CONCLUSIONS: A three-state
      remission-relapse-death model was proposed to quantify and ascertain the
      predictors for the multistate disease progression of small hepatocellular
      carcinomas treated by percutaneous ethanol injection. This model captures the
      risk of recurrence of tumor as well as the primary endpoint of death.

PMID- 16803678
TI  - Molecular interactions of leptin and prostate cancer.
AB  - BACKGROUND: Epidemiological studies have found obesity to be a risk factor for
      prostate cancer. Our prior independent studies in women have reported a strong
      relationship between variants of OB (leptin) gene, body mass index, and age at
      menarche and sporadic breast cancer. The current study investigates an
      association between genetic variants of the human obesity gene, serum leptin
      levels, and body mass index in subjects with prostate carcinoma and in age- and
      gender-matched normal subjects. METHODS: Blood samples from 69 patients with
      prostate cancer and 137 age-matched control subjects were collected. Serum leptin
      level was investigated by radioimmunoassay, and body mass index was calculated.
      Allele sizes were determined via standard polymerase chain reaction. Statistical
      analysis was performed using SPSS10.0 computer software. RESULTS: There was a
      strong association with significantly elevated serum leptin levels, high body
      mass index, and higher frequency of LEPR longer alleles in patients with prostate
      cancer than in control subjects. By contrast, a modest but not significant
      increase in the frequency of LEP short alleles was found in patients with
      prostate cancer as compared with control subjects. Analysis within groups 1 (low
      leptin level and low body mass index) and 2 (other) showed a significant
      association only in group 2, with high frequency of OB gene variants (LEPR long
      alleles and LEP short alleles) in patients with prostate cancer but not in
      control subjects. CONCLUSIONS: These results represent the first report of a
      significant association between specific leptin gene alleles, serum leptin
      levels, and body mass index in subjects with prostate cancer. Consistent with
      prior reports, we also report a significantly elevated serum leptin level in
      patients with prostate cancer, suggesting a strong link with obesity as an
      increased risk factor.

PMID- 16803679
TI  - Can surgical therapy alone achieve long-term cure of melanoma metastatic to
      regional nodes?
AB  - BACKGROUND: Anecdotal reports of melanoma recurrence 15 years after complete
      lymphadenectomy have led to claims that the onset of nodal metastasis invariably
      signals systemic metastases and a terminal diagnosis. Few series in the
      literature are able to refute this assertion. We therefore examined rates of long
      term (> 15-25 years) survival for patients with regional (nodal) melanoma.
      PATIENTS AND METHODS: We performed an analysis of patients with American Joint
      Committee on Cancer stage III melanoma entered into a prospective database for
      the last 30 years. All patients were seen at the treating institution within 4
      months of their diagnosis and monitored thereafter. All patients underwent
      complete lymphadenectomy. Patients receiving melanoma vaccines were excluded.
      Statistical comparisons used Chi-square analysis and the log-rank test. RESULTS:
      At a maximum follow up of 386 months (32 years) for the population of 1422
      patients, rates of 15-, 20-, and 25-year melanoma-specific survival were 36% +/-
      1%, 35% +/- 1%, and 35% +/- 1%, respectively. When patients were stratified by
      clinical status of regional lymph nodes, survival rates were significantly lower
      (P = 0.001) if nodes were palpable. The number of tumor-positive nodes (P <
      0.0001), the pathological primary tumor stage (P = 0.005), age (P = 0.0001), and
      gender (P = 0.002) also were significantly related to long-term survival.
      DISCUSSION: Long-term survivors of melanoma metastatic to regional lymph nodes
      are not uncommon, and the extremely low rate of recurrence beyond 15 years
      suggests that this disease-free interval is usually synonymous with cure.
      Although some risk factors decrease the likelihood of long-term survival, the
      high overall rates of extended survival in all risk groups clearly support
      surgical management as the primary treatment for regional metastatic melanoma.

PMID- 16803680
TI  - Postchemotherapy MRI overestimates residual disease compared with histopathology
      in responders to neoadjuvant therapy for locally advanced breast cancer.
AB  - The utility of breast magnetic resonance imaging in patients receiving
      neoadjuvant chemotherapy is not well defined. We compared serial magnetic
      resonance imaging examinations with histologic posttreatment examinations in
      patients treated with primary chemotherapy for locally advanced breast cancer.
      PATIENTS AND METHODS: Eligible patients with locally advanced breast cancer
      received doxorubicin 60 mg/m(2) and docetaxel 60 mg/m(2) (with granulocyte colony
      stimulating factor support) every 14 days for a maximum of six cycles. Breast
      magnetic resonance imaging was performed at baseline and repeated every two
      cycles. Surgery (either local excision or mastectomy) was performed after six
      cycles in responding or stable patients. Residual tumor size on pathology and
      preoperative magnetic resonance imaging was compared; concordance was defined as
      a < or = 0.5-cm difference. RESULTS: To date, three of 17 enrolled subjects
      (17.6%) attained pathologic complete response, and three additional patients
      attained near pathologic complete response, with residual foci of < or = 1 mm. Of
      these six patients, only one was disease-free by magnetic resonance imaging.
      Discordance between magnetic resonance imaging findings and pathologic evaluation
      was found in four of six patients (66.6%) who obtained pathologic complete
      response or near pathologic complete response. In the three patients in whom four
      axillary lesions were followed with magnetic resonance imaging, discordance was
      found in all four lesions, with magnetic resonance imaging overestimating
      pathologic disease in all cases. DISCUSSION: Our findings caution that magnetic
      resonance imaging may frequently overestimate residual invasive carcinoma after
      neoadjuvant chemotherapy. These results contradict previous studies suggesting
      that postchemotherapy magnetic resonance imaging may underestimate residual
      cancer. The use of magnetic resonance imaging in evaluating response to therapy
      in locally advanced breast cancer should be further studied.

PMID- 16803682
TI  - Clinicopathologic significance of EGFR and Her-2/neu in colorectal
      adenocarcinomas.
AB  - PURPOSE: The purpose of this study was to determine the prognostic impact of
      epidermal growth factor receptor (EGFR) and Her2/neu protein expression in
      colorectal cancer. METHODS: Immunohistochemistry was performed in paraffin
      embedded specimens of 106 colorectal carcinomas for the assessment of EGFR and
      Her-2 expression. The results were correlated with traditional clinicopathologic
      parameters and patient outcome. RESULTS: Membranous expression of EGFR was found
      in 50 cases (47.16%) and cytoplasmic expression in 32 cases (30.19%). Membranous
      overexpression of Her-2 was identified in six cases (5.66%) whereas cytoplasmic
      expression was found in 18 cases (16.98%). The correlation with other
      clinicopathologic parameters demonstrated a statistically significant expression
      of membranous EGFR in the older age group and a statistically significant
      expression of membranous Her-2 in patients with negative lymph nodes. None of the
      other parameters or patient prognosis was associated with EGFR or Her-2
      membranous expression. Cytoplasmic expression was not related with any of
      aforementioned parameters. CONCLUSION: Conventional immunohistochemistry was
      unable to reveal any association between EGFR expression and outcome predicted by
      the biologic role of EGFR in tumor behavior. Her-2/neu is not a pivotal pathway
      in colorectal cancer progression because it seems to be expressed in early stages
      of colorectal cancer.

PMID- 16803681
TI  - Overexpression of glyoxalase system enzymes in human kidney tumor.
AB  - PURPOSE: The purpose of this study was to investigate the messenger RNA
      expression and activity of glyoxalase I and glyoxalase II enzymes in a human
      renal carcinoma (clear cell adenocarcinoma) and in pair-matched normal tissue.
      PATIENTS AND METHODS: Tumor and nontumor pair-matched specimens from the same
      organ were collected during radical nephrectomy from a group of 12 patients of
      both sexes. The mean age of the patients was 52.3 years (range, 50-60 years), and
      none of them had previously undergone neoadjuvant therapy. Gene expression and
      activity were measured by ribonuclease protection assay and current
      spectrophotometric methods, respectively. Intracellular levels of methylglyoxal
      were detected by high performance liquid chromatography. RESULTS: A significant
      increase in the transcription levels of both glyoxalase I (about ninefold) and
      glyoxalase II (about threefold) was observed, compared with the pair-matched
      noncancerous tissues. Glyoxalase I activity was also higher in the pathological
      samples (about 2.5-fold) compared with the control samples and correlated with a
      significant decrease (about twofold) in methylglyoxal concentrations. At
      variance, glyoxalase II activity was significantly lower in pathological tissues
      than in the normal ones. DISCUSSION: Our findings suggest a possible role of the
      glyoxalase system enzymes in the chemoresistance displayed by the kidney tumor.
      In fact, such a refractory behavior involves a decrease in the methylglyoxal
      level, a potent apoptosis activator. In addition, glyoxalase II activity decrease
      in the adenocarcinoma tissue suggests a likely role of the intermediate S-D
      lactoylglutathione by supplying energy in actively proliferating cells. Finally,
      we point out a possible use of glyoxalase I inhibitors as anticancer drugs.

PMID- 16803683
TI  - Paclitaxel hypersensitivity reactions: assessment of the utility of a test-dose
      program.
AB  - Several studies have suggested the usefulness of a test dose of paclitaxel to
      reduce the incidence of hypersensitivity reactions and the resulting cost of drug
      wastage. The aim of this study was to assess the utility of implementing such a
      test dose. METHOD: We retrospectively reviewed the medical charts of patients who
      had received one or two courses of single-agent paclitaxel or a combination
      chemotherapy regimen to calculate hypersensitivity reaction incidence and the
      cost of drug wastage. Thereafter, a paclitaxel test-dose program was routinely
      implemented during the first and second cycles of paclitaxel treatment for all
      patients. Hypersensitivity reaction incidence and drug wastage cost were again
      assessed. RESULTS: Before the routine use of a test dose, 162 patients received
      one or two paclitaxel infusions alone or in combination therapy from January 1,
      1997 to February 28, 2003. Ten (6.2%) patients experienced a hypersensitivity
      reaction; one of them was severe. After implementation of the test-dose program,
      130 patients received 244 test doses (12 mg paclitaxel/10 mL normal saline) with
      an intensified premedication regimen at the first and second cycles of
      chemotherapy from June 28, 2003 to March 2, 2005. Three patients (2.3%)
      experienced a minor hypersensitivity reaction, one immediately after the test
      dose and two during infusion of the full dose despite a well-tolerated test dose.
      Thus, the negative predictive value of the test dose was 98.4%. The overall
      incidence of hypersensitivity reactions experienced during the first or second
      cycle of paclitaxel chemotherapy decreased about 63% compared with the incidence
      before implementation of the test dose (P < 0.20). The test-dose program resulted
      in a 29% increase in the cost of chemotherapy (approximately 6100 dollars for 130
      patients). CONCLUSION: To our knowledge, this is the largest study ever reported
      to test the potential cost-saving benefit of the implementation of a paclitaxel
      test-dose program to prevent hypersensitivity reactions. The results suggest that
      the routine use of a test dose is not a cost-effective measure.

PMID- 16803684
TI  - Prevalence of and risk factors for Barrett's esophagus with intestinal
      predominant mucin phenotype.
AB  - OBJECTIVE: Barrett's esophagus with the intestinal predominant mucin phenotype is
      considered to have a higher malignant potential than that with the gastric
      predominant mucin phenotype. The purpose of this prospective study was to
      investigate the prevalence of and risk factors for Barrett's esophagus with the
      intestinal predominant mucin phenotype in patients undergoing endoscopy. MATERIAL
      AND METHODS: A total of 1699 consecutive patients undergoing
      esophagogastroduodenoscopy were enrolled in the study. A targeted biopsy was
      performed when endoscopically observed columnar-appearing esophagus was stained
      with crystal violet. The sample, histologically evidenced as Barrett's esophagus,
      was immunohistochemically evaluated and categorized as of either gastric or
      intestinal predominant mucin phenotype. All the patients were requested to
      complete the structured questionnaire indicating their symptoms and food
      consumption patterns. Prevalence of and risk factors for Barrett's esophagus with
      and without the intestinal predominant mucin phenotype were investigated.
      RESULTS: Out of 1668 patients, 629 (37.7%) were found to have endoscopic
      Barrett's esophagus. In 333 out of 1668 patients (19.9%), histological studies
      were diagnostic of Barrett's esophagus. One hundred and six of these 333 patients
      (31.8%) had the intestinal predominant mucin phenotype. Age, male gender and the
      presence of hiatal hernia were confirmed by multivariate analysis as the
      independent predictors for the presence of Barrett's esophagus with the
      intestinal predominant mucin phenotype. CONCLUSIONS: Barrett's esophagus with the
      intestinal predominant mucin phenotype was immunohistochemically found in 6.4% of
      all study patients. Older age, male gender and the presence of hiatal hernia were
      the risk factors for the presence of Barrett's esophagus with the intestinal
      predominant mucin phenotype.

PMID- 16803685
TI  - CDX2 expression is increased in gastric cancers with less invasiveness and
      intestinal mucin phenotype.
AB  - OBJECTIVE: CDX2 is an intestinal transcription factor that might be involved in
      the regulation of proliferation and differentiation of intestinal epithelial
      cells. It is well known that both gastric and intestinal phenotypic cell markers
      are expressed in gastric cancers. The aims of this study were to analyze the CDX2
      expression and its relationship with the patients' clinicopathological
      characteristics and the mucin phenotypes by performing immunohistochemistry.
      MATERIAL AND METHODS: A total of 259 gastric cancer cases (122 early and 137
      advanced cancers) were evaluated histologically and phenotypically. CDX2
      expression was assessed by immunohistochemistry. RESULTS: Increased CDX2
      expression correlated with a higher proportion of intestinal-type cancers of
      Lauren and early gastric cancers (p<0.001 and p<0.001, respectively) and a lower
      proportion of perineural invasion and lymph node metastasis (p<0.001 and p=0.003,
      respectively). Increased expressions of intestinal mucin (MUC-2, CD10) and
      decreased gastric mucin (MUC5AC) were associated with an increased CDX2
      expression (p<0.001, p=0.045 and p=0.004, respectively). MUC6 expression was not
      associated with CDX2 expression. There was a significantly increased CDX2
      expression in the intestinal phenotype compared with the other phenotypes
      (p<0.001). CONCLUSIONS: These results suggest that CDX2 might be a useful marker
      in predicting the clinical outcome for patients with gastric cancers.

PMID- 16803686
TI  - Anthropometric correlates of intragastric pressure.
AB  - OBJECTIVE: Obesity may increase intra-abdominal pressure on the stomach leading
      to an increase in intragastric pressure, which in turn induces lower esophageal
      sphincter relaxation, with subsequent reflux. However, the association between
      anthropometric measures of total body as well as abdominal obesity and
      intragastric pressure has not been examined. MATERIAL AND METHODS: This
      prospective cross-sectional study included consecutive patients undergoing
      manometry at an open access Reflux Center. Standardized measurements of body
      weight, height, and waist and hip circumference were prospectively obtained. To
      assess the intragastric pressure, the perfusion port levels of the catheter were
      verified to be at the same vertical height (0 mmHg) inside the patient as they
      were outside the patient during calibration. Correlation between gastric pressure
      and anthropometric measures was calculated and adjusted for demographic features
      and presenting symptoms. RESULTS: A total of 322 patients (67% women) with a mean
      age of 52.5 years were enrolled. The mean values for weight, height, and body
      mass index (BMI) were 77.2 kg, 168 cm, and 27.5 kg/m2, respectively (range 16.0
      52.0, median 27.0). The mean intragastric pressure was 2.9 cm H2O (SD: 1.7).
      There was a weak, positive correlation between gastric pressure and both BMI
      (r=0.11, p=0.05) and waist circumference (r=0.11, p=0.06). The associations
      between gastric pressure and both BMI and waist circumference were relatively
      unaffected by adjusting for several variables including age, indications for
      manometry, race, and gender in a multivariable linear regression model. For each
      unit increase in BMI, there was approximately a 10% increase in intragastric
      pressure. CONCLUSIONS: In this study of consecutive patients with wide-ranging
      BMI values, there was a weak, positive correlation between intragastric pressure
      and both BMI and waist circumference. This indicates that obesity operates to
      increase the risk of gastroesophageal reflux disease (GERD) at least partly by
      increasing intragastric pressure.

PMID- 16803687
TI  - Physicians' attitudes and practices in the evaluation and treatment of irritable
      bowel syndrome.
AB  - OBJECTIVE: Irritable bowel syndrome (IBS) is a common disorder characterized by
      abdominal discomfort and disordered bowel habits. Despite the high prevalence of
      IBS, little is known about how physicians perceive this condition. The aims of
      our study were to measure physicians' understanding of IBS, to assess their
      attitudes towards patients with IBS, and to determine whether there are
      differences in the way Internal Medicine physicians (IM), Family Practice
      physicians (FP), and Gastroenterology physicians (GI) evaluate and treat IBS
      patients. MATERIAL AND METHODS: A survey was sent to 3000 physicians nationwide,
      1000 each to IM, FP, and GI. The survey contained 35 questions assessing
      demographics, the etiology and pathophysiology of IBS, the use of diagnostic
      tests, and practice patterns and attitudes. RESULTS: Of the deliverable
      questionnaires, 501 were returned completed; 472 of the respondents interviewed
      only adult patients, representing the cohort for this analysis. The mean age of
      all respondents was 47; most were men (80%). IM and FP made a new diagnosis of
      IBS 1.3-1.6 times each week, while GI made a new diagnosis 5.4 times each week
      (p<0.0001). Compared with the perceptions of FP and IM, GI felt that IBS patients
      were less sick than other patients (p<0.001), although they required more time
      per visit. More GI compared with FP and IM stated that prior infection and a
      history of abuse were the causes of IBS (p<0.01), while FP were more likely to
      believe that diet was a cause of IBS (p<0.01). GI felt a new diagnosis of IBS
      could be made without further testing 42% of the time. FP and IM felt that one
      third of IBS patients needed referral to a GI. CONCLUSIONS: The attitudes and
      practice patterns of physicians towards patients with IBS differ depending on
      practice specialty. This may be due to differences in training, the ability to
      perform specialized tests, and/or differences in referral patterns. Further
      training may improve the ability of physicians in all specialties confidently to
      diagnose and treat patients with IBS.

PMID- 16803688
TI  - Inhibitory effects of gastric electrical stimulation on ghrelin-induced
      excitatory effects on gastric motility and food intake in dogs.
AB  - OBJECTIVE: To investigate the effects of ghrelin on food intake, gastric motility
      and whether gastric electrical stimulation (GES) is capable of reversing these
      effects of ghrelin in dogs. MATERIAL AND METHODS: Seven healthy dogs were
      equipped with a gastric cannula and electrodes for the measurement of antral
      motility and gastric myoelectrical activity (GMA). Both food intake and gastric
      motility studies were performed in three sessions (control, ghrelin, 20 microg
      and ghrelin plus GES) in randomized order, respectively. After a 28-h fast, the
      animals were provided with unlimited solid food for 1.5 h, 30 min after saline or
      ghrelin injection. Recordings of antral contractions and GMA in each session were
      recorded for 30 min at baseline and 45 min after ghrelin/saline injection in the
      fasting state. GES was performed throughout the experiment initiated 30 min prior
      to the injection. RESULTS: 1) Ghrelin significantly increased food intake from
      475.6+/-75.5 g in the controls to 535.9+/-90.3 g with ghrelin (p=0.04); this
      excitatory effect was reversed by GES. 2) Ghrelin significantly increased the
      motility index from 8.6+/-1.6 in the controls to 16.1+/-2.4 with ghrelin (p=0.01)
      and this effect was also reversed by GES. 3). There were no effects of ghrelin on
      GMA. CONCLUSIONS: Ghrelin induces antral contractions and increases food intake.
      GES is capable of blocking these excitatory effects of ghrelin. These findings
      suggest that GES may inhibit the resistant effect of ghrelin on weight loss.

PMID- 16803689
TI  - Intestinal nitric oxide synthase activity changes during experimental colon
      obstruction.
AB  - OBJECTIVE: The experiments in this study were designed to follow the time course
      of nitric oxide (NO) synthesis in the large bowel during acute mechanical ileus.
      MATERIAL AND METHODS: Occlusion of the mid-transverse colon was maintained for
      420 min in anesthetized dogs. Strain-gauge transducers were used to analyze
      motility changes on the hepatic and lienal flexures, respectively. Constitutive
      NO synthase (cNOS) and inducible NOS (iNOS) activities were determined in tissue
      biopsies, and plasma nitrite/nitrate (NOx) level was measured in the portal
      blood. Following completion of the baseline studies, the animals were treated
      with either 7-nitroindazole (7-NI, selective neuronal NOS inhibitor), or N-nitro
      L-arginine (NNA, non-selective NOS inhibitor). RESULTS: In the sham-operated
      group the cNOS activities differed significantly in the oral and aboral tissue
      samples (oral: 102.9; versus aboral: 62.1 fmol/mg protein/min). The obstruction
      elicited a significant increase in portal NOx and elevated tissue inducible NO
      synthase (iNOS) activity. NNA treatment decreased the motility index in both
      intestinal segments for 60 min, but 120 min later the motility index was
      significantly elevated (2.5-fold increase in the oral part, and 1.8-fold
      enhancement in the aboral segment, respectively). Treatment with 7-NI decreased
      the cNOS activity in the oral and aboral parts by approximately 40% and 70%,
      respectively, and suppressed the motility increase in the aboral colon segment.
      CONCLUSIONS: The motility of the colon was either significantly increased or
      decreased, depending on the type and selectivity of the NOS inhibitor compounds
      applied. NO of neuronal origin is a transmitter that stimulates peristaltic
      activity; but an increased iNOS/nNOS ratio significantly moderates the
      obstruction-induced motility increase.

PMID- 16803691
TI  - Does smoking influence the risk of pouchitis following ileal pouch anal
      anastomosis for ulcerative colitis?
AB  - OBJECTIVE: According to epidemiological studies, smoking habit is strongly
      associated with inflammatory bowel disease. Non-smokers, and especially recent ex
      smokers, have an increased risk of ulcerative colitis (UC). Conversely,
      concerning Crohn's disease, the risk is increased among smokers. Pouchitis is the
      major long-term complication of restorative proctocolectomy for UC, and seems to
      be pathogenetically related to this condition. The aims of this study were to
      test the hypothesis that smoking reduces the risk of pouchitis, and to
      investigate whether cessation of smoking precedes the onset of the inflammation.
      MATERIAL AND METHODS: All living patients operated on for UC with proctocolectomy
      and ileal pouch anal anastomosis (IPAA) between November 1982 and November 1996
      at Sahlgren's University Hospital were included in the study (n=410). Data
      concerning smoking habits and pouchitis were obtained from questionnaires and
      from medical records. The correlation between smoking habits and incidence of
      pouchitis was statistically evaluated by means of a survival test and a
      multivariate analysis, i.e. a Poisson model. RESULTS: In all, 327 patients (80%)
      completed the questionnaires. Ninety-six (29%) of these patients had had at least
      one episode of pouchitis. Smoking habits during follow-up did not significantly
      influence the risk of pouchitis (p=0.29). Nor did smoking habits before and at
      the time of IPAA correlate with the incidence of pouchitis. Women had a decreased
      risk of pouchitis, compared to men (p=0.014). There was a non-significant
      tendency for smoking to increase the risk, which was more pronounced in women.
      CONCLUSIONS: Smoking does not decrease the risk of pouchitis following IPAA for
      UC, and in this respect the pathogenetic model of pouchitis, suggested to be a
      manifestation of UC, is not supported.

PMID- 16803690
TI  - Effect of HLA DQ2, dietary exposure and coeliac disease on the development of
      antibody response to gliadin in children.
AB  - OBJECTIVE: To study the effect of HLA DQ2, dietary history and development of
      coeliac disease (CD) on the induction of antibody response to wheat gliadin and
      cow's milk, beta-lactoglobulin between 1 and 2.5 years of age in children who
      developed CD and in healthy children. MATERIAL AND METHODS: Infants participating
      in a birth cohort study (the ABIS study) in Sweden were studied. Thirty-nine
      children developed CD (=cases), confirmed through biopsy, during follow-up until
      2.5-5 years of age. A total of 181 healthy control children were matched for
      duration of exclusive breast-feeding, birth-weight, gender, maternal smoking and
      season of birth. IgG and IgA antigliadin and anti-beta-lactoglobulin antibodies
      were measured using enzyme immunoassay (EIA). The effects of HLA-risk genotypes,
      DQ2 and DQ8, on CD were also considered. RESULTS: Children who developed CD had
      higher IgG and IgA antigliadin and anti-beta-lactoglobulin antibody levels at 1
      year of age than controls (all comparisons: p<0.001). Similar differences were
      seen between cases with as yet undiagnosed CD by 1 year of age and controls, and
      also when cases were compared with HLA-matched controls. Higher levels of IgG and
      IgA antibodies to beta-lactoglobulin (p=0.003; p=0.001), but not to gliadin, were
      found in treated cases versus controls at 2.5 years of age. HLA-DQ2-positive
      healthy children had lower levels of IgG and IgA antigliadin antibodies than HLA
      DQ2 negative controls at 1 year of age (p=0.004; p=0.012). CONCLUSIONS: Enhanced
      humoral response emerging not only to gliadin, but also to other food antigens
      seems to be primarily associated with CD. Poor induction of antibody response to
      wheat gliadin in healthy children with the HLA-DQ2 risk molecule could at least
      partly explain the genetic predisposition to gluten intolerance and CD.

PMID- 16803692
TI  - Evaluation of the Inflammatory Bowel Disease Questionnaire in Swedish patients
      with Crohn's disease.
AB  - OBJECTIVE: Health-related quality of life (HRQoL) is an important measure of
      inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease
      Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely
      used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the
      validity, reliability and responsiveness of the Swedish translation of the IBDQ
      in patients with Crohn's disease (CD). MATERIAL AND METHODS: Four hundred and
      forty-eight patients with CD completed the IBDQ and three other HRQoL
      questionnaires (Rating Form of IBD Patient Concerns; Short Form-36; and the
      Psychological General Well-Being Index) in connection with their regular visit at
      the outpatient clinic. Disease activity was assessed by the physician on a 4
      point Likert scale. Thirty-two patients who were stable in remission completed
      the questionnaires a second time, 4 weeks later. A total of 418 patients repeated
      all measurements after 6 months. RESULTS: The dimensional scores were highly
      correlated with other measures of corresponding aspects of HRQoL and were
      significantly better in remission than in relapse. High test-retest correlations
      indicated good reliability. Responsiveness was confirmed in patients whose
      disease activity changed over time. However, high correlations between the
      dimensions, poor correlations between items within each dimension, and factor
      analysis all indicated that the original grouping of the items is not valid for
      Swedish CD patients. CONCLUSIONS: Although the Swedish IBDQ has good external
      validity, reliability and responsiveness for patients with CD, our results did
      not support the original grouping of the items.

PMID- 16803693
TI  - Anti-tryptase treatment using nafamostat mesilate has a therapeutic effect on
      experimental colitis.
AB  - OBJECTIVE: Mast cell tryptase has been proposed to be involved in the
      pathogenesis of human inflammatory bowel disease (IBD). Recently, it was reported
      that a low dose of nafamostat mesilate (NM), a serine protease inhibitor that is
      widely used to treat disseminated intravascular coagulation (DIC) and acute
      pancreatitis, can selectively inhibit human tryptase activity. The aim of this
      study was to investigate the anti-inflammatory effects of NM on experimental
      colitis in rats. MATERIAL AND METHODS: Colitis was induced in male Wistar rats
      using an enema of trinitrobenzene sulfonic acid (TNBS) dissolved in 50% ethanol.
      NM or 5-aminosalicylic acid (5-ASA), foundation therapy for mild-to-moderate IBD,
      was administered via the anus once a day on each of the 6 days after
      administration of TNBS. Colonic inflammation was assessed 1 week after TNBS
      administration. RESULTS: Intracolonic administration of TNBS resulted in the
      infiltration of numerous tryptase-positive cells in the colonic mucosa. The
      colonic mucosal injury induced by TNBS was significantly decreased by treatment
      with NM or 5-ASA. The increases in thiobarbituric acid-reactive substances (TBA
      RS), myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and
      cytokine-induced neutrophil chemoattractants-1 (CINC-1) in the colonic mucosa
      were inhibited in the NM group and the 5-ASA group, without significant
      differences between them. CONCLUSIONS: These results indicate that a low dose of
      NM can inhibit the colonic mucosal inflammation induced by TNBS in rats, which
      suggests that anti-tryptase therapy using low doses of NM has excellent potential
      to become a new therapeutic strategy for IBD.

PMID- 16803694
TI  - Effects of statins on experimental colitis in normocholesterolemic rats.
AB  - OBJECTIVE: The results of previous studies suggest that statins have a direct
      anti-inflammatory effect that is not directly related to their cholesterol
      lowering activity. The aim of this study was to investigate the effect of
      simvastatin (SIM) and fluvastatin (FLU) on trinitrobenzene sulfonic acid (TNBS)
      induced colonic inflammation in rats. MATERIAL AND METHODS: The drugs were given
      for 3 days (0.1 and 1 mg/kg day-1; intraperitoneally) after induction of colitis.
      The lesions in the distal colon were scored at the macroscopic and microscopic
      level. Tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase
      (MPO) activity and collagen content were assessed and formation of reactive
      oxygen species and peroxynitrite was monitored by chemiluminescence (CL) assay.
      Trunk blood was collected for the measurement of serum tumor necrosis factor
      (TNF)-alpha level. RESULTS: Treatment with SIM reduced the lesion score of the
      colitis group at macroscopic level (p<0.05), but there was no effect of treatment
      with FLU. The increase in colonic MDA level of the colitis group was reduced by
      both drugs at all doses (p<0.05-0.001). The decrease in GSH and the an increase
      in MPO activity in the colitis group were reversed by SIM at all doses (p<0.01),
      but FLU had no effect. An increase in colonic lucigenin CL value in the colitis
      group was reduced by SIM and FLU at all doses (p<0.001) and an increase in
      peroxynitrite ratio in the colitis group showed a significant reduction in SIM
      treated groups; FLU reduced this effect at a dose of 1 mg/kg (p<0.01). An
      increase in tissue collagen content and serum TNF-alpha level in the colitis
      group was reversed by both drugs at all doses (p<0.001). CONCLUSIONS: SIM and FLU
      seemed to be beneficial in a TNBS-induced rat colitis model through the
      prevention of lipid peroxidation, superoxide generation, cytokine production and
      neutrophil accumulation.

PMID- 16803695
TI  - Adaptive changes of the enterochromaffin and gastrin cells in the rat
      gastrointestinal tract following subtotal colectomy.
AB  - OBJECTIVE: Colectomized patients often have diarrhoea and increased gastric acid
      secretion. Although serotonin influences gastrointestinal (GI) motility and
      secretion, GI serotonin-producing enterochromaffin (EC) cells have not been
      investigated after colectomy, nor have the antral gastrin cells. The aim of this
      experimental study was to investigate the GI tract in rats 8 weeks after subtotal
      colectomy, with particular emphasis on the frequency and distribution of EC and
      gastrin cells. MATERIAL AND METHODS: Immunohistochemical techniques were used to
      identify the two endocrine cell types. RESULTS: The colectomized animals had
      diarrhoea. Body-weight was lower and the small intestine shorter in the
      colectomized animals compared with sham-operated and untreated controls. In the
      two surgically treated groups, the antral mucosa was thinner and the small
      intestinal mucosa was thicker compared with that of the untreated rats, whereas
      the thickness of the rectum of the colectomized rats was increased compared with
      that of the control groups. In the colectomized animals, the number of EC cells
      was increased in the small intestine and rectum, whereas the numbers of both EC
      and gastrin cells were decreased in the antrum. CONCLUSIONS: The results indicate
      that colectomy exerts a significant influence on the GI mucosa and on the
      endocrine cell systems studied. An increased number of EC cells can result in
      alterations in motility and secretion, which may be important in the pathogenesis
      of the diarrhoea that often occurs after colectomy.

PMID- 16803696
TI  - Screening for viral hepatitis among male non-drug-abuse prisoners.
AB  - OBJECTIVE: To describe the prevalence of hepatitis B virus (HBV) and hepatitis C
      virus (HCV) infection and the associated risk factors in a prison population.
      MATERIAL AND METHODS: In this cross-sectional study, from November 2004 to
      February 2005, all 297 newly sentenced prisoners (mean age 37.5+/-11.7 years, age
      range 16-69 years), who had never used illicit drugs received routine blood check
      ups and completed a face-to-face interview. Hepatitis B surface antigen (HBsAg)
      and anti-HCV antibodies were tested using the t-test, chi-square test, and
      logistic regression. RESULTS: Among the 297 subjects, 13.1% were positive for
      HBsAg, 8.4% were positive for anti-HCV, and 1.7% were positive for combined HBsAg
      and anti-HCV. Logistic regression analysis demonstrated that tattooing (odds
      ratio=2.24, 95% CI=1.03-4.88) and an elevated alanine aminotransferase (ALAT)
      level (odds ratio=4.10, 95% CI=1.61-10.40) were independently related to HCV
      infection. CONCLUSIONS: Screening of HBV and HCV infection in prison populations
      remains necessary. Tattooing and elevated ALAT level are identified as the
      related factors of HCV infection.

PMID- 16803697
TI  - Lentiviral gene transfer ameliorates disease progression in Long-Evans cinnamon
      rats: an animal model for Wilson disease.
AB  - OBJECTIVE: Wilson disease is a copper storage disorder caused by mutations in the
      ATP7B gene leading to liver cirrhosis. It has previously been shown that
      lentiviral vectors can govern an efficient delivery and stable expression of a
      transgene. The aim of this pilot study was to prove the principle of a lentiviral
      gene transfer in the Long-Evans cinnamon (LEC) rat, an animal model of Wilson
      disease. MATERIAL AND METHODS: LEC rats were treated either by systemic
      application of lentiviral vectors or by intrasplenic transplantation of LEC-rat
      hepatocytes lentivirally transduced with ATP7B. The ATP7B gene expression was
      analyzed by RT-PCR and immunofluorescence analysis. The therapeutic effect was
      assessed by analysis of liver histology, serum ceruloplasmin oxidase activity,
      and liver copper content. RESULTS: Hepatic expression of the transgene was
      detected at different time-points post-treatment and lasted for up to 24 weeks
      (end of experiment). Liver copper levels were lowered in all treatment groups
      compared to untreated LEC rats. Twenty-four weeks after treatment, the area of
      the examined liver-tissue sections occupied by fibrosis was 48.3-57.9% in
      untreated LEC rats and 10.7-19.8% in rats treated with cell therapy. In
      systemically treated rats, only small fibrous septa could be observed.
      CONCLUSIONS: These data prove for the first time that lentiviral ATP7B gene
      transfer is feasible in Wilson disease. In our pilot study the systemic approach
      was more promising in ameliorating disease progression than the transplantation
      of lentivirally transduced hepatocytes.

PMID- 16803698
TI  - Abdominal pain accompanied by weight loss may increase the diagnostic yield of
      capsule endoscopy: a Korean multicenter study.
AB  - OBJECTIVE: Capsule endoscopy (CE) is approved for the evaluation of obscure
      gastrointestinal (GI) bleeding and its use has increased in the assessment of
      patients with various small-bowel disorders. The yield of CE for indications of
      disorders other than GI bleeding is not yet well described. The aim of the
      present study was to determine in which subgroup of patients with unexplained
      abdominal pain, CE would be a helpful evaluation tool. MATERIAL AND METHODS: The
      results of CE in 110 patients (70 M, 40 F, mean age 50.8+/-14.1 years) with
      unexplained abdominal pain from 12 tertiary referral centers between September
      2002 and September 2004 were retrospectively analyzed. RESULTS: The visualization
      of the small bowel to the cecum was successfully carried out in 69.1% of the
      patients. Nineteen out of the 110 cases revealed positive findings that explained
      the symptoms of the patient (diagnostic yield=17.3%). Diagnosis included small
      bowel stricture (5), Crohn's disease (3), small-bowel tumor (2), radiation
      induced enteritis (1), NSAID-induced enteropathy (1), ischemic ileitis (1),
      diffuse lymphangiectasia (1), and significant erosion or ulceration (5). By
      univariate logistic regression analysis, the positive findings of CE were
      significantly associated with weight loss (odds ratio (OR), 11.9; 95% CI [2.0,
      70.6]), elevated erythrocyte sedimentation rate (ESR) (>20 mm/h) (OR, 11.5; 95%
      CI (1.9, 69.5)), elevated C-reactive protein (CRP) (>or=0.4 mg/dL) (OR, 5.0; 95%
      CI (1.6, 15.9)), and hypoalbuminemia (albumin<3 g/dL) (OR, 23.1; 95% CI (2.4,
      223.1)). Using a multivariate analysis, weight loss was found to be a significant
      risk factor for positive findings of CE (OR, 18.6; 95% CI (1.6, 222.4), p=0.02).
      CONCLUSIONS: The results of this study suggest that CE can be helpful in patients
      suffering from abdominal pain that cannot be explained by established
      examinations, if the pain is accompanied by weight loss.

PMID- 16803699
TI  - Sonographic diagnosis and endoscopic therapy of a biliopancreatic fistula
      complicating a pancreatic pseudocyst.
AB  - This is the first report of a case of biliopancreatic fistula complicating a
      pancreatic pseudocyst diagnosed correctly by transabdominal ultrasound. The
      diagnosis was confirmed by magnetic resonance and endoscopic retrograde
      cholangiopancreatography. The fistula was treated successfully with biliary
      stenting. The clinical and imaging features of this exceptional complication are
      presented along with a brief review of the topic.

PMID- 16803700
TI  - Different approaches to therapy of esophageal granular cell tumor (Abrikossoff
      tumor).

PMID- 16803701
TI  - Existence of a common structural basis for IBS and functional somatic syndromes.

PMID- 16803703
TI  - Topical glucocorticosteroids in rhinitis: mode of action.
AB  - The introduction of nasal glucocorticosteroids, more than 30 years ago,
      represents the most important therapeutic progress in rhinitis management since
      the introduction of the first generation of antihistamines. Our knowledge of the
      mode of action of glucocorticosteroids in the nose has improved as the airway
      mucous membrane of the nose is easily accessible for investigation. However, the
      exact mechanism behind the marked clinical effect remains unclear. The present
      article presents some of the important effects of topical glucocorticosteroids on
      pathophysiological events in the nasal mucosa.

PMID- 16803704
TI  - Otosyphilis mimics immune disorders of the inner ear.
AB  - Syphilis is a well established cause of hearing loss. Sensorineural hearing loss
      may develop in the congenital or acquired form. The clinical course of the early
      acquired and late congenital forms are similar: sudden or rapidly progressive
      bilateral sensorineural hearing loss with mild vestibular symptoms.
      Cochleovestibular involvement in early acquired syphilis has been related to a
      basilar meningitis with lymphocytic infiltration of the labyrinth and VIIIth
      nerve. However, neurosyphilis and inner ear syphilis are not the same disease.
      Prompt diagnosis and treatment with corticosteroids and penicillin are mandatory
      to reduce the immune response and fibrosis of the labyrinth and the endolymphatic
      sac. Unfortunately, early acquired syphilis is frequently overlooked in the
      differential diagnosis of other forms of sensorineural hearing loss, particularly
      autoimmune inner ear disease. Given the increasing number of luetic infection
      cases, especially in immunocompromised patients, this condition should be
      considered in any sexually active patients affected by sudden hearing loss. Cases
      of inner ear syphilis are presented. Immunopathology of luetic inner ear
      infection is discussed and compared with immune disorders of the inner ear.

PMID- 16803705
TI  - Triamcinolone acetonide protects auditory hair cells from 4-hydroxy-2,3-nonenal
      (HNE) ototoxicity in vitro.
AB  - CONCLUSION: Triamcinolone acetonide crystalline suspension (e.g. Volon A) was not
      ototoxic to the auditory hair cells present within organ of Corti explants and
      protected them from an ototoxic molecule, i.e. 4-hydroxy-2,3-nonenal (HNE), that
      is produced within the organ of Corti as a result of oxidative stress-induced
      damage. OBJECTIVES: To test the corticosteroid, triamcinolone acetonide, for
      ototoxicity and otoprotective capacity in organ of Corti explants. MATERIALS AND
      METHODS: Organ of Corti explants excised from 4-day-old rats were the test
      system, HNE was the ototoxin challenge. Hair cell integrity counts were performed
      with fluorescent microscopy on fixed explants stained with FITC-labeled
      phalloidin. Statistical significance was set at p<0.05. RESULTS: Triamcinolone
      acetonide did not affect hair cell integrity in the organ of Corti explants and
      it provided a high level of protection of hair cells against the ototoxic effects
      of a damaging level of HNE as determined by hair cell density counts.

PMID- 16803706
TI  - Analysis of gene expression profiles in cholesteatoma using oligonucleotide
      microarray.
AB  - CONCLUSION: Microarray analysis may be a useful tool to identify some candidate
      genes related to the pathogenesis of cholesteatoma. OBJECTIVE: The aim of this
      study was to investigate gene expression profiles in human cholesteatoma using an
      oligonucleotide chip including 10,115 genes. MATERIALS AND METHODS: Gene
      expression from five cholesteatoma matrices and five normal retroauricular skins
      was analyzed by Macrogen human oligo-chip and the expression levels of some
      selected genes were also confirmed by RT-PCR. RESULTS: In all, 1327 up-regulated
      or 767 down-regulated genes that were over 3 times more prominent in
      cholesteatoma than in skin were identified by 5 samples of microarray data. Among
      these up-regulated or down-regulated genes in cholesteatoma, 291 genes were
      identified in 3 samples or more out of 5 samples as up-regulated expression more
      than threefold in density and 191 genes were down-regulated more than threefold
      in density. RT-PCR of 21 selected genes revealed that those expression levels
      were higher in choleasteatoma than retroauricular skin.

PMID- 16803707
TI  - Persistent geotropic nystagmus--a different kind of cupular pathology and its
      localizing signs.
AB  - CONCLUSION: A persistent geotropic positional nystagmus indicates a dysfunction
      in the lateral semicircular canal with a cupula of less specific weight than the
      surrounding endolymph. It is possible to determine the side of the affected
      cupula by recording the nystagmus pattern in yaw and pitch plane. OBJECTIVES: To
      identify the clinical features in patients with a persistent geotropic positional
      nystagmus, establish lateralizing signs and relate the findings to a
      pathophysiologic mechanism. PATIENTS AND METHODS: Six patients with acute onset
      vertigo of a peripheral origin and persistent geotropic nystagmus were examined
      with videonystagmoscopy and the nystagmus characteristics in different positions
      of the head in yaw and pitch plane were studied. RESULTS: Besides the persistent
      geotropic nystagmus, a zero zone was found with no nystagmus, beyond which the
      nystagmus changed direction when the head of the patient in supine position was
      gradually rotated from side to side. The zero zone was present when the head was
      turned slightly towards one side and is thought to represent a position where the
      affected cupula is aligned with the gravitational vertical. With the head bent
      forwards the nystagmus direction was to the non-affected side and when the head
      was bent backwards to the affected side.

PMID- 16803708
TI  - Asymmetric sensorineural hearing loss evaluation with T2 FSE-MRI in a public
      hospital.
AB  - CONCLUSIONS: T2-weighted fast-spin echo magnetic resonance imaging (MRI) can be
      an economically beneficial protocol for screening patients with asymmetric
      sensorineural hearing loss without other neurologic findings in a public hospital
      population. OBJECTIVE: The goal of this study was to determine if fast spin echo
      T2 MRI is similar to gadolinium-enhanced MRI in evaluating asymmetric
      sensorineural hearing loss in a county hospital population. PATIENTS AND METHODS:
      This was a retrospective chart review of all outpatients seen at a public
      hospital, comprising patients with no other cranial nerve findings who underwent
      gadolinium-enhanced MRI of the internal auditory canal and brain between January
      2002 and September 2003. Patients with >15 dB difference in hearing at one
      frequency or 10 dB hearing difference at two frequencies underwent gadolinium
      enhanced MRI scan with FSE T2 sequence as part of the examination protocol.
      RESULTS: A total of 146 patients were identified who met all the inclusion
      criteria for the study. Of the 146 MRI scans performed, abnormalities were seen
      on 71 of them, the majority of which were inconsequential. No acoustic neuromas
      were identified in our study population. Cost savings of over 100,000 dollars
      would have been realized if only T2 FSE protocols had been used.

PMID- 16803709
TI  - Treatment of idiopathic sudden sensorineural hearing loss.
AB  - CONCLUSION: The therapeutic role of corticosteroids and/or corticosteroids with
      antiviral agents for sudden sensorineural hearing loss (SSNHL) has yet to be
      fully elucidated; however, in cases where deafness is profound and of recent
      onset, a therapeutic trial is indicated. OBJECTIVES: To investigate treatment
      regimens and their efficacies, as well as evaluating the potential prognostic
      correlates and allowing comparison between local and national standards of care
      for SSNHL. PATIENTS AND METHODS: A retrospective evidence-based case series of
      143 patients seen at the University of Rochester, Department of Otolaryngology
      between 1999 and 2002 was investigated. Treatment modalities included (1)
      observation, (2) steroids, and (3) steroids with antivirals. RESULTS: The study
      demonstrates that steroid treatment, alone or in combination with antivirals,
      results in a significant improvement rate compared with observation. Results
      indicate that the more expediently a patient with SSNHL is seen by an
      otolaryngologist, the better their prognosis.

PMID- 16803710
TI  - Comparison of different mobile telephones in Combi40+ users.
AB  - CONCLUSION: Telephone usage is a difficult challenge for cochlear implanted
      patients. A significant number of cochlear implanted patients are able to carry
      on a land-line or mobile telephone conversation. The telephone model may be a
      critical factor for telephone performance. OBJECTIVES: The goals of this study
      were to evaluate speech discrimination through land-line and mobile telephones in
      Combi40+ users, and to compare different mobile telephone models to find out
      which could be more advisable for them. PATIENTS AND METHODS: Eighteen Combi40+
      implantees were tested with CID sentences and bisyllabic words presented through
      land-line and mobile telephones, in both quiet and noisy environments. RESULTS:
      Mean scores for telephonic speech discrimination were over 85% for CID sentences
      and 28-59% for bisyllabic words. The Siemens M55 was superior to the other mobile
      telephones tested.

PMID- 16803711
TI  - The effect of optokinetic stimulation on orientation of sound lateralization.
AB  - CONCLUSIONS: The current study demonstrates that sound lateralization sensitivity
      during interaural time difference (ITD) discrimination may be altered by
      optokinetic (OK) stimulation, and that sound lateralization sensitivity of ITD
      discrimination may be more susceptible to OK stimulation than that of interaural
      intensity difference (IID) discrimination. These data suggest that nystagmus or
      the sensation of self-rotation induced by OK stimulation influences auditory
      afferent information such as sound lateralization. OBJECTIVE: Using dichotic
      sound, the effect of optokinetic stimulation on the orientation of sound
      lateralization was investigated in humans. MATERIALS AND METHODS: Subjects were
      studied by testing ITD and IID discrimination during OK stimulation. RESULTS: At
      90 degrees/s of the light stripes angular velocity the amplitudes for the ITD
      discrimination tests during OK stimulation were significantly greater than those
      either before the beginning of OK stimulation or at 30 degrees/s (p<0.05). No
      significant difference in the amplitude for the IID discrimination test was
      observed between the results obtained before and during OK stimulation. During OK
      stimulation, all subjects felt that their perceptual body axes shifted toward the
      quick phase of OK nystagmus. In 8 of 12 subjects, the median line of amplitude
      for the ITD discrimination test shifted to the quick phase side of the OK
      nystagmus.

PMID- 16803712
TI  - Expression and localization of hepatocyte growth factor and its receptor c-Met in
      inverted papillomas.
AB  - CONCLUSIONS: The results suggest that elevated c-Met expression in combination
      with the co-expression of hepatocyte growth factor (HGF) in the epithelial cells
      of inverted papilloma may proliferate the epithelial cells of inverted papilloma.
      OBJECTIVES: HGF and its receptor, c-Met, have been identified in a variety of
      neoplastic and normal tissue types, implicating these factors in tissue
      regeneration and tumor progression. We investigated the expression and
      distribution of HGF and c-Met in normal nasal mucosa and inverted papilloma, to
      evaluate the possible influence of HGF and c-Met on the development of inverted
      papilloma. MATERIALS AND METHODS: Normal inferior turbinate mucosa and inverted
      papilloma were examined for expression of HGF and c-Met using RT-PCR,
      immunohistochemistry and Western blot analysis. RESULTS: Using
      immunohistochemistry, moderate to high levels of HGF and c-Met protein were
      localized in epithelial cells in inverted papillomas tested in the present study.
      In normal turbinate mucosa immunopositive HGF was detected in the submucosal
      glands where faint staining was found. However, c-Met was noted in the epithelial
      cells and submucosal glands of normal turbinate mucosa. RT-PCR and Western blot
      analysis showed that the expression levels of HGF and c-Met were increased in
      inverted papilloma in comparison with the normal turbinate mucosa.

PMID- 16803713
TI  - Management and outcome after internal carotid artery laceration during surgery of
      the paranasal sinuses.
AB  - CONCLUSIONS: The injury to the cavernous portion of the internal carotid artery
      (ICA) during endonasal sinus surgery is a potentially fatal complication, which
      can be prevented by systematic analysis of preoperative CT imaging in order to
      exclude vascular malformations. Immediate management is critical and requires
      interdisciplinary cooperation between the otolaryngologist and interventional
      neuroradiologist. OBJECTIVE: The purpose of this article is to present two cases
      of injury to the cavernous portion of the ICA during routine endonasal sinus
      surgery for chronic sinusitis and to review the management and outcome of this
      vascular emergency. PATIENTS AND METHODS: A database of all patients surgically
      treated for chronic sinusitis between 1994 and 2004 was reviewed retrospectively.
      Additionally a review of the literature for all published case reports of ICA
      injury was performed. RESULTS: We report two cases of ICA lacerations that
      occurred during routine endoscopic sinus surgery. Both patients were successfully
      treated by employing neuroradiological procedures including balloon and/or coil
      occlusion of various portions of the cavernous ICA. According to the literature
      the outcome depends on the presence or absence of vascular anomalies or aneurysm
      of the ICA with a very poor prognosis in cases of laceration of a pre-existing
      and unrecognized aneurysm.

PMID- 16803714
TI  - Functional inferior turbinosurgery (FITS) for the treatment of resistant chronic
      rhinitis.
AB  - CONCLUSIONS: Modified vidian neurectomy combined with inferior turbinoplasty
      provided an optimal surgical outcome as a treatment for intractable chronic
      rhinitis as evidenced by a relatively long-term follow-up. OBJECTIVE: The study
      was designed to determine the efficacy of submucosal reduction of the inferior
      turbinate and resection of the posterior nasal nerve for the treatment of
      resistant chronic rhinitis. PATIENTS AND METHODS: Fifty-six consecutive patients
      (37 males and 19 females; mean+/-SD age, 26+/-11 years) with resistant allergic
      rhinitis or nonallergic rhinitis with eosinophilia syndrome despite medical
      treatment. Symptomatic improvement including nasal obstruction, nasal discharge,
      sneezing, smell perception, and quality of life and objective evaluation of nasal
      airway resistance and nasal provocation test before and after surgery were
      investigated. RESULTS: The patients showed a remarkable improvement of > or =
      80%, with the exception of two patients who had an approximately 50% reduction of
      the total symptomatic scores. Four of eight patients with anosmia subjectively
      improved whereas the other four patients felt unchanged. All patients who
      underwent rhinomanometry (n=15) and nasal provocation testing (n = 15) both
      before and after surgery showed a significant improvement. There were no
      intraoperative complications. Postoperative epistaxis occurred in one patient.
      One patient complained of a transient hypesthesia of the soft palate and dry eye.
      Nasal mucosal tears were observed in approximately 30% of the patients who
      otherwise showed no severe synechia or persistent crusting.

PMID- 16803715
TI  - Blocking of protease allergens with inhibitors reduces allergic responses in
      allergic rhinitis and other allergic diseases.
AB  - CONCLUSIONS: Allergic responses specific to the corresponding proteases were
      reduced by protease inhibitors, suggesting promise as potent treatments for
      allergic rhinitis and other allergic conditions. OBJECTIVE: Allergic diseases,
      such as allergic rhinitis, are caused by the overproduction of IgE antibodies to
      various allergens. Many reported allergens are proteases that are cysteine,
      serine, aspartic (acid) proteases and metalloproteases. Conjugation of E64
      inhibitor with cysteine protease allergens inhibits the IgE response to the same
      allergens. However, whether inhibitors of the other protease families reduce IgE
      levels and whether protease inhibitors reduce allergic symptoms remain
      controversial. Therefore, we compared the abilities of active and inhibitor
      blocked inactive forms of proteases to generate IgE and allergic symptoms in this
      study to evaluate associations between the allergic response and protease
      inhibitors. MATERIALS AND METHODS: We measured levels of IgE, IgG1, IgG2a, and
      IgG2b enzyme-specific antibodies, and counted frequency of sneezing and nasal
      rubbing behavior in mice immunized with active or inactive forms of bromelain,
      chymotrypsin, chymosin and collagenase (a cysteine protease, a serine protease,
      an aspartic protease and a metalloprotease, respectively). RESULTS: All the
      inhibitors reduced IgE and IgG1 production in response to corresponding enzymes,
      and a cysteine protease inhibitor, E64, decreased nasal symptoms, such as
      sneezing and nasal rubbing.

PMID- 16803716
TI  - Does nasal septal surgery improve quality of life?
AB  - CONCLUSION: In addition to functional ameliorations we have shown that
      septoplasty creates a long-lasting improvement in quality of life in patients
      with nasal septal deviation. OBJECTIVES: The goal of this study was to evaluate
      whether nasal septal surgery alters patients' quality of life. PATIENTS AND
      METHODS: This 7-year retrospective study was undertaken in an otolaryngology
      center. A total of 600 patients who underwent septoplasty with or without
      turbinectomy in the past 7 years for the indication of septal deviation, were
      mailed a questionnaire to assess their quality of life after surgical
      intervention. The questionnaire with 24 items was summarized into 7 subscales
      (overall medical state, nasal symptoms, accompanying symptoms, sleep, practical
      problems, emotions and social life). A visual analog scale was provided to
      measure the patients' general feelings related to their nasal disease. RESULTS:
      In all, 285 patients (47.5%) responded. Analysis of the questionnaire showed an
      improvement in all disease-specific subgroups.

PMID- 16803717
TI  - Viscoelastic measurements after vocal fold scarring in rabbits--short-term
      results after hyaluronan injection.
AB  - CONCLUSIONS: The scarring model resulted in significant damage and elevated
      viscoelasticity of the lamina propria. Hyaluronan preparations may alter
      viscoelasticity in scarred rabbit vocal folds. OBJECTIVES: Vocal fold scarring
      results in stiffness of the lamina propria and severe voice problems. The aims of
      this study were to examine the degree of scarring achieved in the experiment and
      to measure the viscoelastic properties after injection of hyaluronan in rabbit
      vocal folds. MATERIALS AND METHODS: Twenty-two vocal folds from 15 New Zealand
      rabbits were scarred, 8 vocal folds were controls. After 8 weeks 12 of the
      scarred vocal folds received injections with 2 types of cross-linked hyaluronan
      products and 10 scarred folds were injected with saline. After 11 more weeks the
      animals were sacrificed. After dissection, 15 vocal folds were frozen for
      viscoelastic measurements, whereas 14 vocal folds were prepared and stained.
      Measurements were made of the lamina propria thickness. Viscoelasticity was
      measured on intact vocal folds with a linear skin rheometer (LSR) adapted to
      laryngeal measurements. RESULTS: Measurements on the digitized slides showed a
      thickened lamina propria in the scarred samples as compared with the normal vocal
      folds (p<0.05). The viscoelastic analysis showed a tendency to stiffening of the
      scarred vocal folds as compared with the normal controls (p=0.05). There was
      large variation in stiffness between the two injected hyaluronan products.

PMID- 16803718
TI  - Early acquisition of esophageal phonation following tracheoesophageal phonation.
AB  - CONCLUSIONS: Tracheoesophageal phonation appears to participate in early
      acquisition of esophageal phonation, which remains the preferred method of voice
      restoration among patients. Further studies into factors predicting and
      mechanisms underlying acquisition of esophageal phonation among alaryngeal
      patients may provide information facilitating superior quality of life.
      OBJECTIVE: The aim of this study was to examine early acquisition of esophageal
      phonation following tracheoesophageal phonation, and underlying mechanisms and
      preferred phonatory methods for alaryngeal patients who master both
      tracheoesophageal and esophageal phonation. PATIENTS AND METHODS: Subjects
      comprised 44 alaryngeal patients and were divided into three groups: group A
      (n=13), esophageal phonation alone; group B (n=21), tracheoesophageal phonation
      alone; and group C (n=10), patients who acquired esophageal phonation after
      learning tracheoesophageal phonation. RESULTS: The results indicated that
      acquisition of tracheoesophageal phonation significantly accelerated acquisition
      of esophageal phonation to 59.3 days from 184.6 days. Patients in group C stopped
      tracheoesophageal phonation and predominantly used esophageal phonation. No
      factors predicting acquisition of esophageal phonation were identified among
      patients who had mastered tracheoesophageal phonation, including age at time of
      surgery, irradiation, neck dissection, acquisition time of tracheoesophageal
      phonation, and maximum phonation time of tracheoesophageal phonation. No evidence
      of air leakage through the shunt during esophageal phonation was noted in group
      C.

PMID- 16803719
TI  - The prognostic value of proliferating cell nuclear antigen (PCNA) and p53 protein
      expression in patients with advanced nasopharyngeal carcinoma.
AB  - CONCLUSION: p53 protein and proliferating cell nuclear antigen (PCNA) were not
      ideal prognostic indicators in advanced nasopharyngeal carcinoma (NPC). Further
      investigation in searching for other potential biomarkers is needed to enhance
      the prediction of treatment outcome. OBJECTIVE: To assess the prognostic
      significance of p53 protein and PCNA expression in patients with advanced NPC.
      PATIENTS AND METHODS: This study included 46 patients with advanced NPC who had
      received treatment and regular follow-up for at least 5 years. We used
      immunohistochemistry (IHC) staining to assess p53 protein expression and PCNA
      labeling index, and correlate them with pathological subtypes, TNM stage, the
      presence of locoregional recurrence, and 5-year survival rate. RESULTS: p53
      nuclear staining was positive in 32 patients (69.6%). All cases had positive PCNA
      nuclear staining with labeling index (LI) ranging from 6.5% to 92.9% (mean
      53.4%). Only advanced T stage was found to be associated with high PCNA LI.
      Overexpression of p53 and PCNA LI had no impact on 5-year survival in this study
      group.

PMID- 16803720
TI  - Six cases of Forestier syndrome, a rare cause of dysphagia.
AB  - Dysphagia is a common presenting complaint in otolaryngology practice, and there
      are many causes. Forestier syndrome is a rare cause of dysphagia. It is also
      known as diffuse idiopathic skeletal hyperostosis (DISH) syndrome or vertebral
      ankylosing hyperostosis. Forestier syndrome consists of anterolateral
      perivertebral ligament calcification. It was first described by Forestier and
      Rotes-Querol in 1950; diagnosis is primarily radiological and the etiology is
      unknown. In addition to dysphagia Forestier syndrome has been reported to cause
      laryngeal stridor, dyspnea, snoring and hoarseness. Other important symptoms
      associated with Forestier syndrome are stiffness and pain in the back, pain
      related to tendinitis, myelopathy related to core compression associated with the
      ossification of the posterior longitudinal ligament, and pain related to
      vertebral complications such as fracture or subluxation. We report six cases of
      Forestier syndrome as an etiologic factor in dysphagia and present clinical and
      radiological findings.

PMID- 16803721
TI  - Giant cell tumour (central giant cell lesion) of the maxilla.
AB  - The giant cell tumour (GCT) is a benign, locally invasive lesion that accounts
      for about 20% of benign bone tumours. Approximately 2% of all GCTs arise in the
      head and neck region. Giant cell lesions in the craniofacial skeleton other than
      the jaws are uncommon; the majority of them occur in the sphenoid, ethmoid and
      temporal bones. GCT of the maxilla has seldom been described. We present the case
      of an 83-year-old patient with an advanced GCT of the left maxilla who underwent
      en bloc resection through maxillectomy. Reconstruction of the orbitary frame and
      maxilla was performed with autologous calvaria and a temporalis muscle pedicled
      flap. Our successful maxillary reconstruction based on the association between
      autologous calvarial bone sticks bent with titanium miniplates and a temporalis
      muscle pedicled flap allowed the involvement of only one donor area for both hard
      and soft tissues. At 1-year follow-up, our patient showed no evidence of
      recurrent GCT, with satisfactory aesthetic results.

PMID- 16803722
TI  - Surgical management of acute mastoiditis with epidural abscess.
AB  - The prevalence of intracranial complications of acute coalescent mastoiditis in
      children has decreased significantly; however, this clinical problem persists,
      with a relatively high mortality. The common practice for management of acute
      mastoiditis with epidural abscess is mastoidectomy, drainage and placement of a
      ventilation tube, which means that the main pathology is confined to the mastoid
      cavity. We suggest that tympanic exploration is mandatory in certain cases, an
      example of which we present here. We report one case of acute mastoiditis with
      epidural abscess, in which mastoidectomy with tympanic exploration was needed to
      ensure drainage throughout the cavities and to prevent pressure rebuilding in the
      mastoid and tympanic cavities. We stress that if the tympanic membrane is
      thickened and no fluid is drained when placing a pressure equalization tube,
      there could be granulation tissue in the tympanum and tympanic exploration is
      mandatory, especially in a case of acute mastoiditis with intracranial
      complications accompanied by prolonged symptoms.

PMID- 16803723
TI  - Effects of the self-contained breathing apparatus and fire protective clothing on
      maximal oxygen uptake.
AB  - To examine the effects of firefighting personal protective ensemble (PPE) and
      self-contained breathing apparatus (SCBA) on exercise performance, 12 males
      completed two randomly ordered, graded exercise treadmill tests (GXTPPE and
      GXTPT). Maximal oxygen consumption (VO2max) during GXTPPE was 17.3% lower than
      the GXTPT in regular exercise clothing (43.0 +/- 5.7 vs. 52.4 +/- 8.5 ml/kg per
      min, respectively). The lower VO2max during the PPE condition was significantly
      related (r = 0.81, p < 0.05) to attenuated peak ventilation (142.8 +/- 18.0 vs.
      167.1 +/- 15.6 l/min), which was attributed to a significant reduction in tidal
      volume (2.6 +/- 10.4 vs. 3.2 +/- 0.4 l). Breathing frequency at peak exercise was
      unchanged (55 +/- 7 vs. 53 +/- 7 breaths/min). The results of this investigation
      demonstrate that PPE and the SCBA have a negative impact on VO2max. These factors
      must be considered when evaluating aerobic demands of fire suppression work and
      the fitness levels of firefighters.

PMID- 16803724
TI  - Effects of electromyographic and mechanomyographic biofeedback on upper trapezius
      muscle activity during standardized computer work.
AB  - The purpose of this laboratory study was to investigate the effects of surface
      electromyography (EMG)- and mechanomyography (MMG)-based audio and visual
      biofeedback during computer work. Standardized computer work was performed for 3
      min with/without time constraint and biofeedback in a randomized order.
      Biofeedback was given on the basis of an individual preset threshold value for
      the right trapezius EMG and MMG signal and a time factor (repetition of events
      above the threshold). The duration of muscle activity above the preset threshold,
      the right trapezius EMG and MMG root mean square (RMS) values as well as the work
      performance in terms of number of completed graph/mouse clicks/errors, the rating
      of perceived exertion (RPE) and the usefulness of the biofeedback were assessed.
      The duration of muscle activity above the threshold was significantly lower with
      MMG compared with EMG as source of biofeedback (p < 0.05). Biofeedback led to a
      significant decrease in the right trapezius EMG RMS, lower RPE and decreased
      number of errors and mouse clicks, but also decreased number of completed graphs
      (p < 0.05). Audio and visual biofeedbacks were as effective. MMG-based
      biofeedback is a potential reliable alternative to EMG in ergonomics. A lowering
      of the trapezius muscle activity may contribute to diminish the risk of work
      related musculoskeletal disorders development.

PMID- 16803725
TI  - Cognitive diversity and team performance in a complex multiple task environment.
AB  - This article examines the multiple effects of cognitive diversity in teams
      operating complex human-machine-systems. The study employed a PC-based multiple
      task environment, called the Cabin Air Management System, which models a process
      control task in the operational context of a spacecraft's life support system.
      Two types of cognitive diversity were examined: system understanding and team
      specialization. System understanding referred to the depth of understanding team
      members were given during training (low-level procedure-oriented vs. high level
      knowledge-oriented training). Team specialization referred to the degree to which
      knowledge about system fault scenarios was distributed between team members
      (specialized vs. non-specialized). A total of 72 participants took part in the
      study. After having received 4.5 h of training on an individual basis,
      participants completed a 1-h experimental session, in which they worked in two
      person teams on a series of fault scenarios of varying difficulty. Measures were
      taken of primary and secondary task performance, system intervention and
      information sampling strategies, system knowledge, subjective operator state,
      communication patterns and conflict. The results provided evidence for the
      benefits of cognitive diversity with regard to system understanding. This
      manifested itself in better primary task performance and more efficient manual
      system control. No advantages were found for cognitive diversity with regard to
      specialization. There was no effect of cognitive diversity on intra-team
      conflict, with conflict levels generally being very low. The article concludes
      with a discussion of the implications of the findings for the engineering of
      cognitive diversity in teams operating complex human-machine-systems.

PMID- 16803726
TI  - Information processing capacity while wearing personal protective eyewear.
AB  - It is difficult to overemphasize the function vision plays in information
      processing, specifically in maintaining postural control. Vision appears to be an
      immediate, effortless event; suggesting that eyes need only to be open to employ
      the visual information provided by the environment. This study is focused on
      investigating the effect of Occupational Safety and Health Administration
      regulated personal protective eyewear (29 CFR 1910.133) on physiological and
      cognitive factors associated with information processing capabilities. Twenty-one
      college students between the ages of 19 and 25 years were randomly tested in each
      of three eyewear conditions (control, new and artificially aged) on an inclined
      and horizontal support surface for auditory and visual stimulus reaction time.
      Data collection trials consisted of 50 randomly selected (25 auditory, 25 visual)
      stimuli over a 10-min surface-eyewear condition trial. Auditory stimulus reaction
      time was significantly affected by the surface by eyewear interaction (F2,40 =
      7.4; p < 0.05). Similarly, analysis revealed a significant surface by eyewear
      interaction in reaction time following the visual stimulus (F2,40 = 21.7; p <
      0.05). The current findings do not trivialize the importance of personal
      protective eyewear usage in an occupational setting; rather, they suggest the
      value of future research focused on the effect that personal protective eyewear
      has on the physiological, cognitive and biomechanical contributions to postural
      control. These findings suggest that while personal protective eyewear may serve
      to protect an individual from eye injury, an individual's use of such personal
      protective eyewear may have deleterious effects on sensory information associated
      with information processing and postural control.

PMID- 16803727
TI  - Quantifying low back peak and cumulative loads in open and senior sheep shearers
      in New Zealand: examining the effects of a trunk harness.
AB  - Sheep shearing requires shearers to adopt sustained flexed postures for prolonged
      periods of time and has been associated with an increased risk of developing low
      back pain (LBP). However, these postures do not generally result in acute
      compressive values at L4/L5 exceeding the action limit proposed by the National
      Institute for Occupational Safety and Health, despite the high prevalence of LBP
      in this occupation. Therefore, it may not be peak loading that is responsible for
      LBP in this occupation but instead it may be the effect of cumulative loading
      over the course of a workday. The primary purpose of this research was to
      quantify the low back cumulative load exposure in 12 sheep shearers with and
      without the aid of a commercial trunk harness. Results revealed a significant
      reduction in the magnitude of cumulative compression with the use of the trunk
      harness and therefore its use may potentially reduce the risk of injury. The use
      of the trunk harness also reduced the time spent in axially twisted postures,
      which have been associated with LBP. However, using the trunk harness also
      resulted in increased time spent in laterally bent postures, which has been
      associated with increased risk for pain and injury.

PMID- 16803728
TI  - Prediction of slips: an evaluation of utilized coefficient of friction and
      available slip resistance.
AB  - The purpose of this study was to investigate the relationship between measures of
      floor surface slip resistance and an individual's peak utilized coefficient of
      friction (COFU) on the probability of a slip occurring during level walking.
      Video, kinematic and ground reaction force data were recorded simultaneously as
      subjects walked at a self-selected speed during conditions of normal and reduced
      floor surface slip resistance. Peak COFU during weight acceptance was calculated
      and the available floor surface slip resistance was measured using the variable
      incidence tribometer (VIT). Separate logistic regression analyses identified that
      knowledge of the available slip resistance (as measured by the VIT) in
      combination with an individual's peak COFU allowed for greater accuracy in
      classifying slip outcomes (89.5%; p = 0.004), while knowledge of only the
      available slip resistance reduced the accuracy of categorization to 78.9% (p =
      0.021).

PMID- 16803729
TI  - Effect of keyswitch design of desktop and notebook keyboards related to key
      stiffness and typing force.
AB  - This study aimed to compare and analyse rubber-dome desktop, spring-column
      desktop and notebook keyboards in terms of key stiffness and fingertip typing
      force. The spring-column keyboard resulted in the highest mean peak contact force
      (0.86N), followed by the rubber dome desktop (0.68N) and the notebook (0.59N).
      All these differences were statistically significant. Likewise, the spring-column
      keyboard registered the highest fingertip typing force and the notebook keyboard
      the lowest. A comparison of forces showed the notebook (rubber dome) keyboard had
      the highest fingertip-to-peak contact force ratio (overstrike force), and the
      spring-column generated the least excess force (as a ratio of peak contact
      force). The results of this study could aid in optimizing computer key design
      that could possibly reduce subject discomfort and fatigue.

PMID- 16803730
TI  - Right hand advantage in visually guided reaching and aiming movements: brief
      review and comments.
AB  - Although understanding of the organization and control of visually guided
      reaching and aiming movements is still sketchy and incomplete, evidence from
      behavioural studies supports the contention that right-handed individuals
      typically execute aiming movements with better speed, smoothness and consistency,
      and with a greater degree of spatial precision when performing them with their
      right hand. Creative attempts to account for the superiority of the right hand on
      a variety of visually guided reaching and aiming tasks have focused on the
      processing characteristics of the contralateral or left cerebral hemisphere. This
      brief review summarizes the research conducted over the last few decades on the
      subject, highlights the theoretical interpretations offered to explain manual
      asymmetries in the organization and control of goal-directed movements and
      identifies directions for further empirical research. The theoretical and
      practical implications of laterality research efforts along the lines of goal
      directed behaviour are discussed.

PMID- 16803735
TI  - Evidence-based health practice: knowing and using what works for older adults.
AB  - Community-based health care agencies are facing demands for improved outcomes,
      cost-effective programming, and higher customer satisfaction. Implementing
      evidence-based health interventions and programs can help to address these
      challenges. This article provides an overview of evidence-based health practice,
      including the definition and advantages of this approach, other key terms and
      concepts inherent to evidence-based practice, and the tasks and steps necessary
      to its implementation. The article concludes with a list of resources to help
      health care providers learn about, plan, and implement evidence-based health
      interventions and programs.

PMID- 16803736
TI  - Moving from tacit knowledge to evidence-based practice: the Kaiser Permanente
      community partners study.
AB  - For several decades both medical and social work practices have failed to
      consistently include measures to determine the effectiveness of their care and
      practices. This is especially true of care management practices. With the growth
      and aging of our population, this is of particular concern when many of our
      resources for older adults are channeled into services such as geriatric care
      management. This article describes a randomized controlled trial that tested the
      effectiveness of four levels of geriatric care management. Results from this
      study did not support the tacit knowledge of the clinicians in terms of the
      effectiveness of their practices. This article describes the study methods and
      results, and how evidence from this study impacted subsequent service provided by
      geriatric care managers.

PMID- 16803738
TI  - Evidence-based interventions in fall prevention.
AB  - Falls and fall-related injuries, prevalent among older adults, not only have
      devastating consequences for older adults in terms of morbidity and mortality,
      but are also associated with high health care costs. Studies have found that
      multifactorial intervention strategies can effectively prevent and/or reduce
      falls among older adults. The purpose of this article is to describe evidence
      based intervention strategies for community-dwelling older adults. Fall
      prevention efforts are clearly an important area of health promotion and injury
      prevention, and evidence presented in this article provides support for effective
      intervention strategies. Home health care professionals can play a significant
      role in such intervention strategies. However, further research is needed to
      clarify which groups will benefit most from specific intervention programs.

PMID- 16803737
TI  - Implications of translating research into practice: a medication management
      intervention.
AB  - Through programs such as the Administration on Aging's Evidence-Based Prevention
      Initiative, researchers and practitioners are developing translational research
      studies seeking to implement rigorously tested, evidence-based interventions in
      new practice settings and evaluate the continuing effectiveness of these
      interventions. One such translational study is the Community-Based Medications
      Management Intervention (CBM Intervention), a collaborative effort to implement a
      medication management screening and intervention protocol in community-based
      waiver care management programs. The overall goals of the CBM Intervention are to
      implement an evidence-based medication management intervention in a California
      Medicaid waiver care management program, and to evaluate the effect of client-,
      intervention-, and organizational-level characteristics on resolving identified
      medication problems. This article presents the need for improved medication
      management in a frail, community-dwelling, older adult population and describes
      the CBM Intervention as an example of translating an evidence-based practice
      beyond its original efficacy trial in a home healthcare program into a care
      management program. It discusses critical factors involved in translating
      research into practice using a translational research framework, Promoting Action
      on Research Implementation in Health Services (PARIHS). Our experience suggests
      that although implementing research into practice can positively impact client
      care, professional skill enhancement and organizational effectiveness, this is
      very challenging work requiring signification facilitation for successful
      outcomes.

PMID- 16803739
TI  - Translating evidence-based physical activity interventions for frail elders.
AB  - The population shift to an older America has initiated a great deal of interest
      in the impact of evidence-based physical activity interventions on older adults.
      Physical activity for older adults has tremendous benefits and is recognized as
      one of the most powerful health interventions for improving seniors' ability to
      function and remain independent in the face of active health problems and yet the
      majority of all older adults remain largely sedentary. To date, few programs have
      been developed that apply these important research findings in physical activity
      to frail older adults living in the community. The purpose of this article is to
      review past and current trends addressing increasing physical activity in the
      frail elderly population at home. An exemplary model of integrating an evidence
      based intervention into community-based care management programs is described.
      Barriers encountered when implementing evidence-based physical activity
      interventions with frail elderly at home and recommendations for future work in
      this area are discussed.

PMID- 16803740
TI  - Moving evidence-based interventions to populations: a case study using social
      workers in primary care.
AB  - This article describes a study to expand a proven evidence- based practice for
      depression to a population-based intervention for frail older adults. Problem
      Solving Therapy (PST) has been proven effective in reducing depression and other
      mental health conditions in cognitively intact adults in many studies. The
      current study employs a randomized controlled trial to test the effectiveness of
      a social work intervention for frail older adults that uses PST to address
      depression and other psychosocial issues. The intervention employs Master's
      trained social workers integrated into a large primary care practice. The study
      population is comprised of home-dwelling older adults with multiple chronic
      conditions, a recent history of unnecessary hospitalizations, and no more than
      mild cognitive impairment.

PMID- 16803742
TI  - Barriers and facilitators to replicating an evidence-based palliative care model.
AB  - Recognition of the difficulties involved in replicating evidence- based
      interventions is well documented in the literature within the medical field.
      Promising research findings are often not translated into practice, and if they
      are, there is a significant time gap between study conclusion and practice
      adoption. The purpose of this article is to describe the barriers and
      facilitators encountered by two managed care organizations while replicating an
      evidence-based end of life in-home palliative care model. Using Diffusion of
      Innovation Theory as a theoretical framework, results from focus groups and
      interviews with the project's clinical, administrative and research teams are
      presented and recommendations made for improving translational efforts. The
      process of replicating the end of life in-home palliative care model clearly
      illustrated the key elements required for successfully diffusing innovation.
      These key elements include marketing and communication, leadership,
      organizational support and training and mentorship. This qualitative process
      study provides clear, real world perspectives of the myriad of challenges
      encountered in replicating an evidence-based project.

PMID- 16803743
TI  - Adolescent religious commitment and their consumption of marijuana, cocaine, and
      alcohol.
AB  - Using the National Education Longitudinal Study (NELS) data set from the 1988
      1992 period, this study used longitudinal data to assess the effects of student
      religious commitment on the marijuana, cocaine, and alcohol consumption of those
      children. The results of this study support the notion that a high level of
      religious commitment among adolescents reduces their likelihood of consuming
      marijuana, cocaine, and alcohol. Religiously committed adolescents consumed
      marijuana, cocaine, and alcohol less frequently and were less likely to be under
      the influence of marijuana and alcohol at school than their less religious
      counterparts. There were, however, no differences in the likelihood of religious
      and less religious twelfth graders to be under the influence of cocaine while at
      school. The study also indicates that the use of marijuana, cocaine, and alcohol
      by adolescents was associated with lower levels of academic achievement than
      those students who did not use these substances.

PMID- 16803744
TI  - Minority physicians and selective contracting in competitive market environments.
AB  - This study used a framework of strategic behavior to further explore MCOs'
      physician contractual decision making. Using data from a cross-sectional mail
      survey of 1,215 physicians, we tested the assumption that a physician's patient
      profile is related to higher rates of contract denial or termination when
      adjusted and unadjusted for the level of managed care market competition. As
      minority physicians serve more minority patients who tend to have a poorer health
      status than white patients, we expected greater rates of contract denials and
      terminations for minority physicians when models are unadjusted for the level of
      market competition. In models adjusted for competition, we expected physician and
      patient race to be unrelated to MCO contractual decisions. We found physician
      ethnicity was not a predictor for contract denials or terminations, but patient
      ethnicity was a predictor for contract denials and terminations. When market
      competition is accounted for, the differences were almost unchanged.

PMID- 16803746
TI  - The impact of deinstitutionalization of psychiatric hospitals on psychological
      distress of the community in Canada.
AB  - OBJECTIVE: There has been a plethora of studies that evaluate the impact of
      deinstitutionalization of psychiatric services, but they have not examined
      whether this policy has had an impact on the broader community. The present study
      addresses this gap by evaluating the impact of the deinstitutionalization of
      psychiatric hospitals on the mental health of the general population in Canada.
      METHOD: This research builds on an empirical analysis of 40 years of the process
      of deinstitutionalization of psychiatric services in Canada (Sealy and Whitehead
      2004). An experimental design is simulated through the use of a derived
      construct, earlier vs. later deinstitutionalization, in order to test whether the
      policy of deinstitutionalization has achieved the goal of decreasing levels of
      psychological distress for people in the community. This study attempts to
      rectify some of the methodological limitations of past evaluations by
      standardizing the rates of deinstitutionalization among the provinces and taking
      into consideration the impact of the interaction among levels of perceived social
      support and the various social correlates of psychological distress. Cross
      sectional data from the 1994/95 (n = 16,989) and the 1998/99 waves of the
      National Population Health Survey (n = 14,682) are used to measure levels of
      psychological distress. RESULTS: Provinces that implemented this policy earlier
      have levels of psychological distress that are significantly lower than the
      provinces that implemented deinstitutionalization later. All high risk groups
      (people with lower levels of income and education, younger people, people living
      in urban areas) have significantly lower levels of psychological distress in
      1998/99 (as compared to 1994/95) with the exception of single parents in the
      provinces that implemented deinstitutionalization earlier. CONCLUSION: Based on
      the NPHS, the earlier implementation of deinstitutionalization is associated with
      lower levels of psychological distress of the community as compared to the
      provinces that implemented deinstitutionalization later.

PMID- 16803745
TI  - Nurses respond to healthcare restructuring: the transformation of the
      Massachusetts Nurses Association.
AB  - The most recent period of Massachusetts healthcare system reorganization began in
      the early 1980s. In part, this has been a response to soaring healthcare costs,
      countering them with diminished reimbursements. To decrease labor costs and
      survive in an increasingly competitive and market-driven healthcare environment,
      hospitals downsized and laid off nursing staff. Patient care and safety has
      concomitantly suffered. These efforts severely challenged nurses' status.
      Radicalized rank and file members of the Massachusetts Nurses Association
      mobilized against the association leadership's weak efforts to protect nurses'
      social and economic interests and the deteriorating quality of care. They
      transformed an association whose main focus was supporting nursing's professional
      image to one which became an activist labor union of professional workers. The
      history of this often contentious transformation is presented here within the
      context of these healthcare system changes. The MNA's successes and pending
      challenges within the Massachusetts healthcare system are also discussed.

PMID- 16803747
TI  - Unveiling patterns of salary inequity: suggested measurement strategy for health
      care organizations.
AB  - This paper focuses on how potential race related salary inequity and racial
      discrimination patterns can be measured in health care organizations.
      Incorporating ethical principals to the measurement strategy helps conceptualize
      potential patterns of salary inequity. Convergent validity assessment through
      triangulation method allows for the measurement of parallelism, correspondence,
      and the affirmation of major findings. The most important benefit of the
      suggested strategies is the ability to assess and identify how discrimination may
      be occurring in organizations.

PMID- 16803741
TI  - Depression care for the elderly: reducing barriers to evidence-based practice.
AB  - This paper provides an overview of five key bodies of evidence identifying: (1)
      Characteristics of depression among older adults -- its prevalence, risk factors
      and illness course, and impact on functional status, mortality, use of health
      services, and health care costs; (2) Effective Interventions, including
      pharmacologic, psychotherapies, care management, and combined intervention
      models; (3) Known Barriers to depression care including patient, provider and
      service system barriers; (4) Effective Organizational and Educational Strategies
      to reduce barriers to depression care; and (5) Key Factors in Translating
      Research into Practice. There is strong empirical support for implementing
      strategies to improve depression care for older adults.

PMID- 16803749
TI  - A randomized controlled trial of psychosocial interventions using the
      psychophysiological framework for Chinese breast cancer patients.
AB  - This study aimed to investigate the psychophysiological outcomes of different
      psychosocial interventions for breast cancer patients. Participants were randomly
      assigned into 3 intervention groups, namely, Body-Mind-Spirit (BMS), Supportive
      Expressive (SE), and Social Support Self-Help (SS) groups; a no-intervention
      group was used as control. Salivary cortisol was used as the physiological stress
      marker. Distress level, mental adjustment, emotional control, and social support
      were measured. Data were collected at baseline, 4 month, and 8 month. Preliminary
      results indicated that BMS intervention produced the greatest and the most
      sustained effects. It enhanced positive social support, reduced psychological
      distress, emotional control, and negative mental adjustment. Total salivary
      cortisol was lowered after 8 months. Most participants in SE groups indicated the
      treatment helpful, but changes in psychophysiological outcomes were not
      statistically significant. Participants in SS groups seemed less likely to
      benefit from the intervention. The no intervention control group indicated a
      reduction in social support. These outcomes suggest that active professional
      intervention is more likely to yield therapeutic effects. In particular,
      psychosocial intervention attending to the spiritual dimension contributes to
      positive outcomes.

PMID- 16803750
TI  - The role of meaning in advanced cancer-integrating the constructs of assumptive
      world, sense of coherence and meaning-based coping.
AB  - This study used qualitative methods to elicit the thoughts and attitudes of
      patients with advanced cancer. Our two interrelated aims were to explore how
      participants experience and apply meaning; and to consider whether this
      experience can be understood within an integrated framework of assumptive world
      (AW), sense of coherence (SOC) and meaning-based coping (MBC). Using semi
      structured interviews, 26 conversations were held overall with 10 participants.
      Transcriptions were analysed for themes of lived-experience and for evidence of
      the principal elements of AW, SOC, and MBC. Findings suggest three interrelated
      domains that form an adaptive pathway towards coherence and sense of self. While
      this pathway is essentially linear it is also responsive to the ongoing stressful
      nature of advanced cancer.

PMID- 16803751
TI  - Assessing for suicide risk in depressed geriatric cancer patients.
AB  - Although several studies have identified different factors that increase the risk
      for suicide in the elderly, depression, especially in cancer patients, puts
      people at even greater risk. In geriatric patients with co-morbid illnesses,
      depression is often undiagnosed or overlooked because of the assumption that it
      is to be expected. When patients with cancer are diagnosed with depression, it is
      imperative that clinicians have a clear-cut tool for assessing and identifying
      signs of suicidality in order to develop a treatment plan to manage the patient.
      This article delineates the steps involved in conducting a systematic suicide
      risk assessment in depressed elderly patients with cancer.

PMID- 16803752
TI  - Silent voices and invisible walls: exploring end of life care with lesbians and
      gay men.
AB  - The needs and desires of lesbians and gay men with cancer at the end of their
      lives are not fundamentally different from any other dying individual's needs.
      There are, however, significant legal restrictions and societal attitudes that
      can negatively affect the dying experiences of lesbians and gay men. Lesbians and
      gay men face many challenges at the end of their lives, including issues of
      disclosure in the healthcare setting, discrimination, misconceptions, legal and
      financial barriers and the disenfranchised grief of surviving same-sex partners.
      Oncology social workers can play a prominent role in advocating for these
      individuals to allow for dignity and support in spite of these barriers and
      provide effective interventions to help in assisting lesbians and gaymen with
      healthcare decision-making and end-of-life care planning.

PMID- 16803753
TI  - Pain and symptom management clinical, policy, and political perspectives.
AB  - During the last decade, the prevalence of cancer pain and the reality of
      undertreatment have been well documented in both adults and children. There has
      been a proliferation of educational and regulatory activity setting an
      expectation that management of pain is a priority. At the same time, pain has
      come to the attention of the media, advocacy groups, industry, legislators,
      regulators and litigators creating an environment where this rich and
      multidimensional aspect of oncology care has moved beyond a clinical focus and
      opening up a range of opportunities for oncology professionals to participate as
      experts and leaders. The ethical underpinnings of the mandate to treat pain and
      attend to suffering compels psychosocial clinicians to advocate for the care of
      patients and consider participating in an informed way in the policy, legislative
      and political issues that flourish around the treatment of pain.

PMID- 16803754
TI  - Helping patients make decisions about complementary and alternative treatments:
      the social work role.
AB  - Increasingly people are using complementary and alternative modalities (CAM) to
      cope with and manage cancer. Many patients, however, do not know how to access
      credible information and make informed treatment decisions. Social workers are in
      a unique position in the healthcare team to facilitate patients' decision-making
      about CAM. Skills and techniques to educate patients and to help them communicate
      with their healthcare practitioners about CAM are described. The authors
      introduce questions patients should ask to make better-informed treatment
      decisions, and describe social work interventions to help patients explore their
      choices in the context of personal history, meaning, beliefs and lifestyle.
      Lastly, the position of the social worker vis a vis the institution and its
      stance on CAM is explored.

PMID- 16803755
TI  - Survivors of childhood sexual abuse diagnosed with cancer: managing the impact of
      early trauma on cancer treatment.
AB  - The incidence of survivors of childhood sexual abuse (CSA) diagnosed with cancer
      is unknown. It is estimated that one in three women and one in six men in the
      United States are survivors of CSA. Survivors of CSA diagnosed with cancer are
      presented with multiple and potentially accumulating traumas. The re-traumatizing
      nature of a cancer diagnosis and treatment affects all elements of the CSA
      survivor's care and may impede her/his treatment. To date, the impact of CSA on
      the medical treatment of people with cancer has been unexplored with the existing
      studies on female survivors of CSA with cancer focusing on the post-treatment
      experience and their higher incidence of sexual dysfunction. This article
      describes the impact of CSA on the cancer treatment of 18 survivors of CSA and
      the clinical interventions used to address the unique psychosocial needs of this
      population. Anecdotal information suggests that the survivors of CSA may find
      aspects of the cancer experience reminiscent of their history of abuse. All 18
      survivors of CSA experienced distressing memories of their abuse during their
      cancer treatment. Fifteen CSA survivors presented traumatic memories that were
      inaccessible to conscious thought processes prior to their cancer diagnosis.
      Psychodynamic interventions address issues of disruption in the cancer treatment,
      non-adherence, and difficulties in relationships with the health care team.
      Containment of intense affect and distressing thoughts rather than exploration
      improved CSA survivors' adherence with cancer treatments. The acquisition of self
      comforting skills helped CSA survivors feel less re-victimized by their cancer
      experience. The establishment of an environment of internal and external safety
      improved communication with the health care team. Health care/psychosocial
      clinicians' awareness and use of appropriate interventions can minimize the
      affects of re-traumatization and enhance the CSA survivor's treatment experience.

PMID- 16803756
TI  - Introduction: the state of our knowledge on SM.

PMID- 16803757
TI  - Sadomasochism and the social sciences: a review of the sociological and social
      psychological literature.
AB  - Recent literature about sadomasochism in Sociology and Social Psychology is
      reviewed. Studies include survey research and questionnaire studies, content
      analyses, ethnographic research, and critical essays. The current state of our
      knowledge of sadomasochism, including its defining characteristics,
      sadomasochistic identities, and sadomasochistic subcultures is briefly
      summarized.

PMID- 16803758
TI  - Differences and similarities between gay and straight individuals involved in the
      sadomasochistic subculture.
AB  - Results from some new analyses as well as a selective review of the results of
      six empirical studies on a self-identified sample of sadomasochistically-oriented
      individuals (22 women and 162 men) with an emphasis on differences between gay
      and straight participants are presented. The gay male respondents seemed to be
      better educated, to hold white-collar occupations and to be more sadistically
      oriented. The gay male respondents became aware of their sadomasochistic
      preferences and had their first experiences at an older age. They showed a
      preference for leather outfits, anal intercourse, rimming, dildos, wrestling,
      special equipment and uniform scenes, and the straight male respondents for
      verbal humiliation, mask and blindfold, gags, rubber outfits, cane whipping,
      vaginal intercourse, cross dressing, and straitjackets, and different role plays
      except for uniform scenes. Four separate sexual themes were identified:
      hypermasculinity; administration and receiving of pain; physical restriction and
      psychological humiliation. Gay male participants showed a preference for
      hypermasculinity and straight men respondents for humiliation. The number of
      lesbian respondents was too low to draw any definite conclusions. Differences
      between gay and straight male sadomasochists in the present sample were found.
      Clearly, sadomasochism cannot be thought of as a unitary phenomenon: People who
      identify themselves as sadomasochists mean different things by these
      identifications.

PMID- 16803759
TI  - Sexual spanking, the self, and the construction of deviance.
AB  - Using interview and observation data from a group of consensual, heterosexual
      adults interested in sexual spanking, I describe members' sexual stories and
      stigma neutralization techniques. Sexual stories are situated within broader
      cultural contexts that help individuals construct meaning and identities. I
      describe group members' stories about their initial interest in sexualized
      spankings. Focusing on a specific event at one party, I show how these stories
      help to create scene-specific stigma neutralization techniques. Participants
      strive to differentiate themselves from sadomasochistic activities and to create
      normative behavioral expectations within their scenes. I conclude that all of
      this can ultimately be viewed as part of the complex sexual adaptations that
      people make.

PMID- 16803760
TI  - 24/7 SM slavery.
AB  - This study describes the nature of 24/7 SM slavery as practiced within the SM
      (sadomasochistic) community. These SM participants, who attempt to live full-time
      in owner-slave roles, represent a small proportion of those with SM interests. SM
      slaves have not been studied systematically to determine if and how they differ
      from other SM practitioners. An online questionnaire was used to obtain responses
      from individuals who self-identified as slaves. A total of 146 respondents
      participated, 53% female and 47% male, ranging in age from 18 to 72. We explored
      the depth of their relationships, how well they approximated "slavery," and how
      their relationships were structured to maintain distinct roles. Data showed that
      in long-term SM slave relationships, a power differential exists which extends
      beyond time-limited SM or sexual interactions. Owners and slaves often use
      common, daily life experiences or situations, such as the completion of household
      chores, money management, and morning or evening routines, to distinguish and
      maintain their respective roles. In addition, contrary to the perception of total
      submission, results revealed that slaves exercise free will when it is in their
      best interests to do so. These relationships were long-lasting and satisfying to
      the respondents.

PMID- 16803761
TI  - Mainstreaming kink: the politics of BDSM representation in U.S. popular media.
AB  - This article explores nonpractitioners' understandings of and responses to the
      increasingly mainstream representation of BDSM in U.S. media, focusing on the
      film Secretary (Shainberg, 2002). Survey, focus group, and interview data
      indicate that popular images of SM promote the acceptance and understanding of
      sexual minorities through two mechanisms: acceptance via normalization, and
      understanding via pathologizing. Rather than challenging the privileged status of
      normative sexuality, these mechanisms reinforce boundaries between
      protected/privileged and policed/pathological sexualities. Instead of celebrating
      increased representation, this article argues that political energy might be
      directed toward the desire that the popularity of BDSM representations signifies:
      the desire to encounter authentic, undisciplined, and noncommodified
      representations that would transgress the sexual norms of American postmodern
      consumer culture.

PMID- 16803762
TI  - Understanding sadomasochism: an empirical examination of four perspectives.
AB  - Three studies assessed current understandings of sadomasochism (SM). In Study 1
      questionnaires testing four academic views of SM were administered to individuals
      who self-defined as involved in SM. The psychoanalytic, psychopathology/medical
      model, radical feminist and escape-from-self perspectives were not supported.
      Study 2 examined "virtual" sadomasochism as a source of information about
      sadomasochists in the real life world. Cluster analyses indicated that real-life
      and virtual sadomasochists share unique sexual proclivities. Study 3 examined an
      alternative view that identifies power as the commodity of importance in SM play.
      Content analysis of online SM encounters indicated that both "top" and "bottom"
      role-players used several specific techniques to create a power differential.
      These studies suggest that, contrary to many academic theories, power, and not
      the giving and receiving of pain, is at the core of SM.

PMID- 16803763
TI  - The spanner trials and the changing law on sadomasochism in the UK.
AB  - In the United Kingdom in 1989 a group of gay men who had been engaging in
      consensual SM activities were put on trial and found guilty of assault. The
      dominants/tops were charged with assault, and the men who participated in the
      activities as "bottoms" or submissives were convicted of aiding and abetting
      assaults upon themselves. This article discusses these Spanner trials--as they
      came to be called--and the issues of consent and privacy on which they were
      argued. UK and potentially European law are being subjected to pressure for
      redefinition as a result of the Spanner case, as SM practitioners are beginning
      to experience the implications and fallout from the prosecutions. While there
      have been proposals to reform the laws about what has been deemed self
      destructive and socially dangerous behavior, little has changed to date. The
      story of the prosecutions and appeals, and the pressures for a new legislative
      approach to decriminalize consensual SM, will be situated in the context of
      public interest claims to control the private actions of individuals in the
      interest of public health. Differences in interpretation that occur when gay men
      are involved as compared to heterosexual couples will also be discussed.

PMID- 16803764
TI  - Negotiating limits: the legal status of S/M in the United States.
AB  - This paper reviews the origin of the concept of sadomasochism and its treatment
      by the American legal system. Relevant court cases and corollary issues such as
      the rights to privacy and sexual freedom, child custody, domestic violence, and
      employment discrimination are profiled. Organizations created by the gay, lesbian
      and heterosexual leather communities to create accurate public awareness of the
      SM subculture, and their programs of education and activism, are discussed and
      prospects for effective legislative change evaluated.

PMID- 16803765
TI  - Discrimination of SM-identified individuals.
AB  - The belief that sadomasochism (SM) is violence or abusive behavior has resulted
      in harassment, physical attacks, and discrimination against SM-identified
      individuals. Historically, they were often opposed by self-identified feminists.
      One reason the women who practiced SM were targeted was the official opposition
      to sadomasochistic practices promulgated by the National Organization for Women
      (NOW). Current statistics of incidents of discrimination, harassment and physical
      attacks against SM-identified individuals and SM groups are compiled by the
      National Coalition for Sexual Freedom (NCSF).

PMID- 16803766
TI  - S/M (sadomasochistic) interests as an issue in a child custody proceeding.
AB  - This article describes a child custody case centered on the fitness of the
      mother, who was involved in an SM relationship with her live-in boyfriend.
      Although the investigation confirmed that no child abuse had occurred, that the
      child was unaware of the mother's sexual interests, that there were no incidents
      of inappropriate sexual activities in front of the minor, and that the child was
      doing well, the court severely limited the mother's visitation and custody
      arrangements and ended her alimony. Practitioners of alternative sexual
      lifestyles have not fared well in child custody hearings, and this case is no
      exception. The present case indicates how the family court system can be biased
      against sexual minorities in general and SM practitioners in particular. In
      addition, the present case demonstrates how the DSM diagnostic criteria can be
      misused in dealing with alternative lifestyle practitioners. Recommendations for
      further education of the court and for future research are made.

PMID- 16803767
TI  - The ICD diagnoses of fetishism and sadomasochism.
AB  - In this article we discuss psychiatric diagnoses of sexual deviation as they
      appear in the International Classification of Diseases (ICD-10), the
      internationally accepted classification and diagnostic system of the World Health
      Organization (WHO). Namely, we discuss the background of three diagnostic
      categories: Fetishism (F65.0), Fetishistic Transvestism (F65.1), and
      Sadomasochism (F65.5). Pertinent background issues regarding the above categories
      are followed by a critique of the usefulness of diagnosing these phenomena today.
      Specifically, we argue that Fetishism, Fetishistic Transvestism, and
      Sadomasochism, also labeled Paraphilia or perversion, should not be considered
      illnesses. Finally, we present the efforts of an initiative known as ReviseF65,
      which was established in 1997, to abolish these diagnoses.

PMID- 16803768
TI  - Psychotherapeutic issues with "kinky" clients: clinical problems, yours and
      theirs.
AB  - People whose sexual repertoire includes BDSM, fetish, or other "kinky" practices
      have become increasingly visible, on the Internet, in the real world, and in
      psychotherapists' offices. Unfortunately, the prevailing psychiatric view of BDSM
      remains a negative one: These sexual practices are usually considered
      paraphilias, i.e., de facto evidence of pathology. A different, affirming view of
      BDSM is taken in this paper. After defining BDSM and reviewing common
      misconceptions, a variety of issues the practitioner will face are described.
      These include problems of countertransference, of working with people with newly
      emerging sexual identities, working with spouses and partners, and discriminating
      between abuse and sexual "play."

PMID- 16803769
TI  - Investigating bias in psychotherapy with BDSM clients.
AB  - There is a concern among consensual BDSM participants that they will receive
      biased care from mental health professionals. Results are presented of an
      anonymous Internet-based survey administered to both BDSM-identified individuals
      who have received psychological care and to mental health professionals. The
      survey included socio-demographic data and invited participants to write
      narrative accounts of biased or culturally sensitive care, from which common
      themes were identified. Mental health providers (N=17) responded in fewer numbers
      than those who identified as BDSM-identified participants (N=175). Descriptive
      characteristics of the sample will be discussed. Themes from the qualitative data
      may be useful in informing the future development of guidelines for practitioners
      to work more responsibly with clients who identify as members of this sexual
      minority group.

PMID- 16803770
TI  - Learning from extraordinary lovers: lessons from the edge.
AB  - This paper discusses lessons about sexuality and eroticism gleaned from those who
      engage in extraordinary sex, even though such relationships have typically been
      classified as pathological. What can clinicians learn from those who seek and
      attain uncommon sexual relations? Such individuals' sexual epistemology, goals,
      understanding of the nature and spectrum of sexual and erotic relations,
      communication strategies and "outcome" criteria can provide valuable lessons for
      those who treat sexual problems or aim to overcome sexual mediocrity. For
      example, while traditional sex therapy often focuses on what is on the surface,
      some SM participants are interested in the meanings that lie at a deeper level.
      Whereas conventional clinicians may focus on enabling particular sexual acts
      (especially heterosexual intercourse), SM participants are more apt to be
      concerned with the varied spectrum of underlying purposes motivating these acts.
      Whereas many couples are willing to settle for merely functional sex, SM
      practitioners may be more interested in contact that necessitates intense, erotic
      connection; sophisticated communication of subtle differences in intent; and
      eventuates in profound self-knowledge and transcendent levels of intimacy.
      Illustrative case examples are provided.

PMID- 16803775
TI  - Communities respond to elder abuse.
AB  - This article traces the development of services to prevent and treat elder abuse
      over a twenty-year time span. It begins by describing the various forms of elder
      abuse and the challenges they pose to service providers and program developers.
      Also described are abuse reporting statutes, the roles of various agencies
      involved in abuse investigations and responses, services commonly needed by
      victims, funding sources, and common impediments to service delivery.

PMID- 16803776
TI  - A policy perspective on elder justice through APS and law enforcement
      collaboration.
AB  - The policy issues involved in the social problem of elder victimization could
      fill volumes. Even the policy issues involved in the new concept of elder justice
      are multi-faceted. Through the lens of a policy analysis perspective, the
      history, ideologies, politics, social movements, and economics of policies that
      promote the collaboration between adult protective services and law enforcement
      are examined. The analysis of state and local policies as well as a promising
      federal legislative initiative will, hopefully, help policy advocates understand
      from where the movement toward collaboration between adult protective services
      and law enforcement has come as well as where it may be headed.

PMID- 16803777
TI  - Social inclusion: an interplay of the determinants of health - new insights into
      elder abuse.
AB  - Social and economic exclusion and inclusion are receiving growing attention and
      study in North America for their usefulness as a conceptual framework that
      addresses the many dimensions of poverty and inequality in our society. A
      discussion of social and economic exclusion/ inclusion flows naturally out of the
      population health field in which the social determinants of health have become
      well-established over the last twenty years or more. The determinants of health
      provide a broad and inclusive outline within which to situate prevention, early
      detection and effective intervention of the abuse of older persons. A Social
      Inclusion Lens offers exciting possibilities for addressing the issue of elder
      abuse and neglect.

PMID- 16803778
TI  - Self-determination and elder abuse do we know enough?
AB  - This article explores the principle of self-determination as it relates to
      victims of elder abuse and neglect. Using newspaper accounts and cases from the
      author's practice and consulting files, various factors influencing the
      professional's interpretation of this principle are explored. The notion that
      self-determination allows victims of abuse and neglect to refuse intervention is
      challenged. The author concludes that the principle of self-determination and the
      notion of competency are overly simplified in the social work and elder abuse
      literature and may be misused by allowing abused older victims to choose to
      remain in often life-threatening situations. Special focus is given to Adult
      Protection Service worker, but the author asserts that protecting older people,
      assisting in creative interventions and developing needed services is a shared
      professional responsibility.

PMID- 16803779
TI  - Use of a single page elder abuse assessment and management tool: a practical
      clinician's approach to identifying elder mistreatment.
AB  - Elder abuse is a growing, alarming public health issue. As health care
      professionals, our challenge is to balance our duty to protect the safety of the
      vulnerable elder with the elder's right to self-determination. Clinicians in busy
      practice settings across the continuum of care as well as community-based social
      workers, emergency medical system, police, and banking personnel are
      collaborative partners needing tools that focus on early recognition, assessment,
      intervention, and management of elder abuse. A simple one-page tool that provides
      principles of assessment and management, best practice guidelines and screening
      questions will hopefully serve to raise awareness of this important public health
      issue and maintain a high index of suspicion for elder abuse, neglect and
      financial exploitation.

PMID- 16803780
TI  - An elder abuse shelter program: build it and they will come, a long term care
      based program to address elder abuse in the community.
AB  - This article describes how The Hebrew Home for the Aged at Riverdale (the Hebrew
      Home), a non-profit geriatric care center, has established one of the nation's
      first long term care based elder abuse prevention and intervention programs for
      elderly living in the community. This program, known as the Weinberg Center for
      Prevention, Intervention and Research in Elder Abuse (the "Weinberg Center"),
      received start-up funding in the form of a matching grant challenge from the
      Weinberg Foundation of Baltimore, which has a history of funding innovative
      geriatric programs throughout the United States. Utilizing the Hebrew Home's
      extensive integrated service model, a multidisciplinary team works with a network
      of private and governmental agencies. This model was designed based upon the
      needs of this population as described in the nascent research, evaluation of the
      few programs in existence, and the emerging state of elder abuse as a matter of
      public policy. The goals are to increase public awareness, intervene to make the
      home safe, and provide a secure and fulfilling short or long term shelter.
      Research in prevalence and efficacious use of the shelter is being conducted.

PMID- 16803781
TI  - Consumer fraud and the elderly: a review of Canadian challenges and initiatives.
AB  - Financial abuse is the most common type of elder abuse. Consumer fraud, a form of
      financial abuse perpetrated by criminals who do not know the victim, is not well
      studied. Seniors represent a disproportionate percentage of the victims of
      consumer fraud. This article reviews the data on the prevalence of consumer fraud
      (primarily telemarketing scams) in Canada. It examines the reasons why Canadian
      seniors are targets of fraud. It also describes many unique initiatives developed
      at the local, provincial and national level in Canada to educate seniors and
      those who care for them about the types of scams and the risks of fraud.

PMID- 16803783
TI  - Ethical and psychosocial issues raised by the practice in cases of mistreatment
      of older adults.
AB  - Intervention regarding older adult mistreatment raises many questions for
      practitioners. They have to interact with the victim, the abuser, and, in many
      cases, with both of them at the same time. In such cases, five themes emerge from
      the literature review on psycho-social and ethical issues in practice:
      practitioners' pre-construction and axiological frameworks, victims' capacity,
      confidentiality versus collaboration between practitioners or between agencies,
      social and family responsibilities and the balance between competing values in
      practice. Practitioners are well placed to offer a critical reflection on their
      practice and on ways of improving it. The goal of our qualitative study is to
      identify issues and ethical dilemmas in elderly mistreatment situations as
      represented in the discourses of practitioners in reference to interventions in
      their psychosocial practice. Sixteen practitioners from the public and community
      (non-profit organization) sectors were interviewed using a practice history
      approach. This paper presents the main ethical and psychosocial issues raised by
      practitioners and some ideas to improve the practice. It is motivated by the
      crucial question haunting the practitioners' minds: "How far should we go?"

PMID- 16803782
TI  - Psycho-educational support groups for older women victims of family mistreatment:
      a pilot study.
AB  - Few programs for domestic violence victims have been evaluated for effectiveness.
      This gap is even more pronounced for elder abuse service interventions. The study
      presented here is intended to address this gap by using an experimental research
      design to evaluate outcomes of an elder mistreatment psycho-social support group
      pilot for cognitively unimpaired older female victims of mistreatment by family
      members and significant others for whom they are providing care or support. The
      support group model used for the study adapts amodel designed by NOVA House, an
      elder abuse shelter program in Manitoba, Canada. The study was funded by the
      Hartford Foundation Geriatric Social Work Faculty Scholars Program. While the
      significance of study findings is limited by the small number of pilot
      participants, the model intervention and evaluation instrument developed for the
      study may be utilized for study replication.

PMID- 16803784
TI  - Elder abuse and neglect among veterans in Greater Los Angeles: prevalence, types,
      and intervention outcomes.
AB  - This study examined the prevalence, types, and intervention outcomes of elder
      abuse/neglect among a veteran population. A review of medical records of 575
      veterans who had received services from the Veteran's Affairs Geriatric
      Outpatient Clinic in Los Angeles during a three-year period found 31 veterans
      (5.4%) who had an elder abuse report filed on their behalf. Prevalence of elder
      abuse/neglect was higher among older (80+) and Caucasian and African American
      veterans. Eight of 31 victims suffered from more than one type of elder abuse
      including self-neglect. Financial abuse and self-neglect were the most commonly
      reported types. Family members were perpetrators in the majority of the cases,
      excluding self-neglect. However, three-quarters of financial abuse cases were
      committed by non-family members. Almost one-half of the victims had dementia and
      eight were clinically depressed. The most common intervention was to move victims
      from their unsafe home into a nursing home or board and care facility, followed
      by conservatorship arrangement. These interventions were most frequently used for
      victims with dementia, and conservatorship was often arranged with another type
      of intervention, such as a move to a nursing home. Victims who remained at home
      received conservatorship or outside supportive services or a combination of both.
      This study calls for more comprehensive and systematic research on elder
      abuse/neglect at multi-settings in order to generate useful information for
      prevention and detection of, and effective intervention in elder abuse and
      neglect in the veteran population.

PMID- 16803785
TI  - Hearing the voices of abused older women.
AB  - This paper focuses on a qualitative research process that gathered responses from
      64 older women aged fifty and older on their experience of violence and abuse.
      What older women said about abuse in their lives supports the use of a feminist
      framework as well as the age based analysis of the elder abuse field. Some
      respondents spoke of abuse from childhood into their later years. Some spoke of
      partners witnessing or experiencing abuse as children. Some women express concern
      about possible abuse by their adult children of their own children. Abused older
      women like younger women need a safe environment, emotional support, advocacy,
      information, and peer support. While it is important to consider the perspectives
      and knowledge of service providers when developing policy and practice on abuse
      of older women, it is critical to ask the women survivors of abuse or neglect
      what they believe would benefit them, and others in similar situations.

PMID- 16803786
TI  - Effects of dependency on compliance rates among elder abuse victims at the New
      York City Department for the aging, elderly crime victim's unit.
AB  - A study was conducted at the New York City Department for the Aging Elderly Crime
      Victim's Unit (ECVU) to examine the relationship between dependency and
      compliance rates. Dependency was defined by the total score for each case on the
      Victim Dependency Scale and Abuser Dependency Scale. Compliance was defined as
      the act of accepting a referral and compliance rates were determined by counting
      the total number of referrals the victim accepted. Findings indicated that the
      only factor associated with compliance rates was if the abuser had a mental
      illness/substance abuse problem. If the abuser did have this problem, the victim
      was significantly more likely to accept a referral for services as compared to
      victims whose abusers did not have a mental illness/substance abuse problem (t=
      2.774, df=36.899, p<.01). The authors offer explanations as to why this research
      was important and the implications it has on future research.

PMID- 16803787
TI  - Multimedia hearing handicap inventory: reliability and clinical utility.
AB  - PURPOSE: This preliminary study evaluated the test-retest reliability, internal
      consistency reliability, and listener reactions to the design and functional
      utility of the Multimedia Hearing Handicap Inventory (MHHI). METHOD: Participants
      were 51 adults exhibiting hearing sensitivity ranging from normal hearing to
      severe hearing loss. Different test-retest sequences, using different
      combinations of the long and short programs of the MHHI, were administered to 3
      experimental groups composed of 17 participants each. An exit interview was used
      to evaluate the MHHI's clinical utility. RESULTS: Results revealed the MHHI to
      have high test-retest reliability and high internal-consistency reliability, and
      thus to have statistical properties similar to those of the original screening
      versions of the Hearing Handicap Inventories for Adults and for the Elderly.
      Participant feedback regarding the MHHI's overall clinical utility, the
      informational content of its long program, and the Hearing Profile feature was
      highly positive. CONCLUSIONS: Results demonstrate the clinical potential of a
      multimedia approach in advancing the audiologic rehabilitation process.

PMID- 16803788
TI  - Initial audiologic assessment of infants referred from well baby, special care,
      and neonatal intensive care unit nurseries.
AB  - PURPOSE: The purpose of the study was to evaluate the effectiveness of a 2-hr
      initial audiologic assessment appointment for infants referred from area
      universal newborn hearing screening (UNHS) programs to a clinical audiology
      department in an urban hospital. METHOD: A prospective auditory brainstem
      response (ABR)-based protocol, including clicks, frequency-specific tone bursts,
      and bone-conducted stimuli, was administered by 10 audiologists to 375 infants.
      Depending on the ABR findings, additional test options included distortion
      product otoacoustic emissions (DPOAEs), high-frequency tympanometry, and/or
      otologic examination. RESULTS: In 88% of the 2-hr test sessions, at least 4 ABR
      threshold estimates were obtained (i.e., bilateral clicks and either a 500- or
      1000-Hz tone burst and a 4000-Hz frequency tone burst for the better ear). The
      incidence of hearing loss was significantly different across nursery levels: 18%
      for Level I (well baby), 29% for Level II (special care), and 52% for Level III
      (neonatal intensive care unit). Hearing loss type was defined at the initial
      assessment for 35 of the 51 infants with bilateral hearing loss based on bone
      conduction ABR, latency measures, DPOAEs, high-frequency tympanometry, and/or
      otologic examination. CONCLUSIONS: Our findings indicate that a 2-hr test
      appointment is appropriate for all nursery levels to diagnose severity and type
      of hearing loss in the majority of infants referred from UNHS. Examination by an
      otolaryngologist within 24-48 hr further defines the hearing loss and facilitates
      treatment plans.

PMID- 16803789
TI  - A case study of an emerging community-based early hearing detection and
      intervention program: part I. Parents' compliance.
AB  - PURPOSE: This is the first of a 2-part series of articles that describe and
      assess an emerging community-based early hearing detection and intervention
      program. This study investigated parents' compliance for accessing services for
      their infants at 5 levels in the process from referrals through subsequent follow
      up during a 3-year period. Compliance was defined as parents' follow-through with
      professionals' recommendations and appointments for their infants' hearing health
      care. METHOD: Investigators retrospectively reviewed the charts of 51 infants who
      were referred from a regional hospital's newborn hearing screening program to a
      private practice office and were seen from March 2000 to February 2003. RESULTS:
      Compliance was 100% for initial hospital inpatient screening and for outpatient
      rescreening but decreased throughout the referral process. All of the parents of
      babies with hearing loss complied, and their infants were diagnosed by age 3
      months and received audiologic or otologic intervention by age 6 months. Only
      half of those who needed and opted for hearing aids complied and began
      habilitative intervention by age 6 months. CONCLUSIONS: Although compliance for
      initial and follow-up screening was excellent and met goals for national
      benchmarks, compliance for intervention services showed room for improvement.

PMID- 16803790
TI  - A case study of an emerging community-based early hearing detection and
      intervention program: part II. Team building with otolaryngologists and
      pediatricians using a survey approach.
AB  - PURPOSE: Physicians are vital team members of early hearing detection and
      intervention programs (EHDIPs), particularly in encouraging parents to comply
      with recommendations for follow-up services for their infants in universal
      newborn hearing screening programs (UNHSPs). This study describes a survey
      approach to help audiologists partner with otolaryngologists and pediatricians in
      EHDIPs. METHOD: We developed and mailed a 19-item questionnaire to all 12
      otolaryngologists and 66 pediatricians potentially involved in a community-based
      EHDIP. The questionnaire assessed respondents' demographic data and knowledge of,
      experiences with, and attitudes toward the service-delivery continuum of UNHSPs.
      RESULTS: The overall response rate was 45%; all 12 otolaryngologists responded
      (100%; data from 7 were analyzed), and 23 pediatricians responded (34.8%; all
      were analyzed). Generally, they were positive toward and knowledgeable about
      UNHSPs and believed that (a) parent/infant bonding is unaffected by screening,
      (b) hearing reevaluations following medical services are important, (c)
      audiologists perform their role adequately, (d) it is important that hearing
      losses be identified and interventions begun before infants reach 6 months of
      age, (e) UNHSPs deserve funding, and (f) their role is important, but the
      physicians also wanted improvements in parent education and referral/follow-ups.
      CONCLUSION: The survey method was effective in identifying participating
      physicians' informational needs and attitudes toward UNHSPs, and in designing
      outreach programs for them.

PMID- 16803791
TI  - The application of self-efficacy principles to audiologic rehabilitation: a
      tutorial.
AB  - PURPOSE: The purpose of this tutorial is to provide a comprehensive overview of
      the self-efficacy framework and its application to audiologic rehabilitation.
      METHOD: A literature review was conducted on self-efficacy and its relevance to
      successful interventions in several health domains. Specific recommendations were
      presented for audiologic rehabilitation procedures that will enhance self
      efficacy. CONCLUSIONS: As is the case in other health domains, clinical
      intervention by audiologists will be more effective when incorporating a self
      efficacy framework in the audiologic rehabilitation process.

PMID- 16803792
TI  - Serial position effects for acoustic stimuli among children with and without
      hearing loss.
AB  - PURPOSE: This study investigated serial position effects on auditory sequential
      organization among children with hearing loss and with normal hearing. METHOD:
      Forty-eight children were divided into 4 equally sized groups: 2 groups of 6-7
      year-olds and 2 groups of 9-10-year-olds. Each age group had 12 children with
      normal hearing and 12 children with sensorineural hearing loss. Participants were
      asked to reproduce auditory sequences of verbal (syllables /ba/ and /da/) and
      nonverbal (1-kHz pure tone and a wideband noise) elements by pressing associated
      buttons. RESULTS: No evidence of a recency effect was found, but a primacy effect
      was observed in the participants' performance under most experimental conditions.
      Normal hearing participants in the 6-7-year-old group were better at reproducing
      3 to 5 verbal items than their counterparts with hearing loss, independent of
      item sequence position. CONCLUSION: Results suggest that, regardless of hearing
      status, all children use similar mnemonic strategies.

PMID- 16803793
TI  - Hearing screening in the neonatal intensive care unit: follow-up of referrals.
AB  - PURPOSE: The goal of this study was to examine the rate of diagnostic testing
      after newborn hearing screening (NHS) referral, evaluate timeliness of follow-up,
      and evaluate the use of multilevel auditory brainstem response (ABR) in screening
      of high-risk infants. METHOD: Telephone interviews were conducted with parents of
      infants who had been admitted to a neonatal intensive care unit from 1999 to 2002
      and referred on NHS. An ABR screen was combined with a multilevel ABR (40, 70,
      and 90 dB nHL) for referrals. RESULTS: Parents of 206 infants participated; 69%
      of the infants underwent diagnostic follow-up. Of those with follow-up, 37% had
      normal hearing, 38% had hearing loss, and parents were unsure of hearing test
      results for 25%. Follow-up by 6 months of age occurred for 13% in 1999,
      increasing to 31% by 2002. Infants who did not pass their screening in both ears
      had confirmed hearing loss in 56% vs. 25% in those who passed in 1 ear. Also, 67%
      of infants with bilateral pass levels of 90 dB nHL or more had confirmed hearing
      loss, vs. 32% in all others. CONCLUSIONS: Timely follow-up after NHS referral in
      our program has improved over time. Multilevel ABR may facilitate allocation of
      appropriate resources to track and ensure follow-up in infants at high risk for
      hearing loss.

PMID- 16803794
TI  - Test-retest reliability of in situ unaided thresholds in adults.
AB  - PURPOSE: The purpose of this study was to examine test-retest reliability of in
      situ unaided thresholds measured using a handheld hearing aid programmer coupled
      to a hearing aid transducer in adults with normal hearing. METHOD: Randomized in
      situ thresholds at 4 octave frequencies were established in 1 ear of 43 adults
      twice using the Widex Diva SP3 device with the stimulus generated by and
      transduced through a Widex Diva SD-9 behind-the-ear hearing aid. Insert earphone
      tips were used in each of the measures to couple the hearing aid/transducer to
      the ear canal. RESULTS: Mean decibel differences between the test and retest
      thresholds were less than 1 dB at each frequency. Using an 80% statistical test
      criterion, results revealed test-retest reliability within 5 dB for all
      frequencies: 98% at 500 Hz, 100% at 1000 and 2000 Hz, and 93% at 4000 Hz.
      CONCLUSIONS: Test-retest reliability of in situ unaided thresholds using the
      SP3/SD-9 device is equivalent to that of currently accepted audiometric
      procedures.

PMID- 16803795
TI  - Comparison of performance on the hearing in noise test using directional
      microphones and digital noise reduction algorithms.
AB  - PURPOSE: Difficulty understanding speech in background noise is one of the most
      common complaints of hearing aid users. In modern hearing aids, directional
      microphones (d-mics) are considered the method of choice in improving signal-to
      noise ratio, with demonstrated improvement in speech-perception-in-noise tasks.
      On the other hand, digital noise reduction (DNR) algorithms, in commercially
      available products, are considered to provide comfort but not significant
      assistance in improving speech perception in noise. In practice, these 2
      technologies are often used in conjunction, but few studies have evaluated their
      interaction and the resultant effect on speech perception in noise. The purpose
      of this study was to evaluate the effect on speech performance of using d-mics
      and DNR in isolation as well as in conjunction in the presence of background
      noise. METHOD: This study evaluates the performance of 16 experienced adult
      hearing aid users on the Hearing in Noise Test when each technology was activated
      independently and then simultaneously in 4 commercially available hearing aids.
      RESULT: Approximately 50% of our participants performed better with both d-mics
      and DNR activated in conjunction, while the other 50% performed best in the d-mic
      only condition. When considering statistically significant differences in
      performance only, a reduction or improvement in performance was observed in 17%
      and 14% of the conditions, respectively. CONCLUSION: A direction for further
      research would be to identify predictive variables that could help the
      audiologist determine an individual's preference a priori.

PMID- 16803796
TI  - Vaccines, epidemics, pandemics and us.

PMID- 16803797
TI  - Pulling teeth into the genomics era.

PMID- 16803798
TI  - Trusting your instincts.

PMID- 16803799
TI  - Endodontic therapy.

PMID- 16803800
TI  - Informed consent.

PMID- 16803801
TI  - Psychosocial confusion.

PMID- 16803802
TI  - Watching and waiting.

PMID- 16803803
TI  - Gene discovery for dental anomalies: a primer for the dental professional.
AB  - BACKGROUND: Thousands of inherited human disorders have been catalogued to date,
      but the underlying genetic causes of less than 20 percent of those disorders have
      been discovered. TYPE OF STUDIES REVIEWED: The completion of the Human Genome
      Project (HGP) has made available the DNA sequence of all 24 human chromosomes,
      thereby allowing the localization of all human genes and, ultimately,
      determination of their function. Disease gene discovery is being expedited
      greatly by the data from the HGP, thereby paving the way for determination of the
      genetic etiology of most of these disorders. RESULTS: While most dental anomalies
      can severely affect patients' quality of life, they are not fatal, which makes
      multigenerational families with these disorders available for study. These
      families are invaluable for genetic studies. Despite this fact, the discovery of
      genes underlying non-syndromic dental anomalies has lagged behind that for
      anomalies affecting other organ systems. The authors present an overview of the
      methodologies of disease gene identification using hypodontia, which is one of
      the most common anomalies of the dentition, to illustrate the application of
      these principles. CLINICAL IMPLICATIONS: An understanding of the advances in
      human genetics should inspire the practicing dental professional to ascertain
      whether a dental anomaly is inherited and, if so, work with a human geneticist to
      identify its underlying genetic mechanism.

PMID- 16803804
TI  - Restless legs syndrome: manifestations, treatment and dental implications.
AB  - BACKGROUND: The authors reviewed the clinical features, epidemiology,
      pathogenesis and risk factors, medical management, dental findings and dental
      management of patients with restless legs syndrome (RLS). TYPES OF STUDIES
      REVIEWED: The authors conducted a MEDLINE search for the years 2000 through 2004
      using the key terms "restless legs syndrome," "epidemiology," "pathophysiology,"
      "treatment" and "dentistry." They selected articles published in English in peer
      reviewed journals for further review, and they gave preference to articles
      reporting randomized controlled trials. CONCLUSIONS: RLS is a neurological
      disorder that is characterized by unpleasant sensations in the legs that occur at
      rest, especially at bedtime. These symptoms cause an irresistible urge to get out
      of bed and move the legs to relieve the discomfort, thereby delaying sleep onset
      and resulting in fatigue and dysphoria the next day. CLINICAL IMPLICATIONS: The
      prevalence of dental disease may be extensive in patients with RLS because of
      diminished salivary flow resulting from the medications used to treat RLS.
      Patient education, saliva substitutes and anticaries agents are indicated.
      Special precautions must be taken when prescribing or administering sedative
      hypnotic agents that are likely to have adverse reactions with the medications
      used to treat RLS.

PMID- 16803805
TI  - The clinical usefulness of surface electromyography in the diagnosis and
      treatment of temporomandibular disorders.
AB  - BACKGROUND: This article presents a comprehensive review of the recent literature
      regarding the scientific support for the use of surface electromyography (SEMG)
      in diagnosing and treating temporomandibular disorders (TMDs). TYPES OF STUDIES
      REVIEWED: The authors conducted a Medline search involving human studies using
      the key words "surface electromyography or electromyography" and "masticatory
      muscles or temporomandibular disorders or craniomandibular disorders." They also
      reviewed relevant articles regarding the clinical usefulness of SEMG based on
      reliability, validity, sensitivity and specificity, as well as additional
      references included in some of the articles. RESULTS: The clinical use of SEMG in
      the diagnosis and treatment of TMD is of limited value when one considers
      reliability, validity, sensitivity and specificity as measurement standards. SEMG
      does not appear to contribute any additional information beyond what can be
      obtained from the patient history, clinical examination and, if needed,
      appropriate imaging. CONCLUSIONS: Clinically, the determination of the presence
      or absence of TMD does not appear to be enhanced by the use of SEMG. However, the
      modality may be useful in a meticulously controlled research setting. CLINICAL
      IMPLICATIONS: SEMG has limited value in the detection or management of TMD and in
      some instances may lead to unnecessary dental therapy as a solution for those
      disorders.

PMID- 16803806
TI  - Sex differences among dentists regarding eating disorders and secondary
      prevention practices.
AB  - BACKGROUND: The purpose of this cross-sectional study was to assess sex
      differences among dentists pertaining to current behaviors and behavioral beliefs
      with regard to eating disorders. METHODS: The authors collected data via a self
      administered paper-and-pencil questionnaire from a randomized sample of 350
      practicing male and female dentists. RESULTS: The results showed a low level of
      practice regarding secondary prevention (that is, measures leading to early
      diagnosis and prompt intervention) of eating disorders. The authors found
      statistically significant differences, with more female than male dentists
      reporting that they assessed patients for oral cues (P < .001), more female
      dentists reporting that they provided specific dental care instructions (P =
      .038) and more female dentists referring patients who have oral signs of eating
      disorders (P = .028). They also found sex differences with regard to mediating
      factors. Female dentists had greater knowledge of oral manifestations of eating
      disorders (P = .001), greater knowledge of physical cues of anorexia nervosa (P <
      .001), greater perception of the severity of anorexia nervosa (P = .007) and
      greater knowledge of physical cues of bulimia nervosa (P < .001). CONCLUSIONS:
      Although the dentist may be the first health care provider to assess oral effects
      of eating disorders, his or her involvement may be influenced in part by sex and
      sex-related health beliefs. CLINICAL IMPLICATIONS: Female dentists may be more
      sensitive to oral cues related to women's health issues. Further research is
      warranted to explore the mediating factors regarding secondary prevention of
      eating disorders.

PMID- 16803807
TI  - A retrospective clinical evaluation of two-unit cantilevered resin-bonded fixed
      partial dentures.
AB  - BACKGROUND: The authors conducted a study to examine the clinical performance of
      two-unit cantilevered resin-bonded fixed partial dentures (RBFPDs) that were
      inserted at The Prince Philip Dental Hospital, University of Hong Kong. METHODS:
      The authors recalled patients who had received two-unit cantilevered RBFPDs at
      least 24 months before the recall examination. The authors recorded the following
      data: patient's sex and age, operator's experience, prosthesis cementation date,
      endodontic treatment if performed, bone support, tooth mobility, the presence of
      shim-stock contacts on the abutment or pontic in intercuspal position, and the
      presence of aproximal axial contacts adjacent to the prosthesis. They also
      recorded the date of any debonding with subsequent treatment. They asked the
      patients qualitative questions about their prostheses. RESULTS: A total of 269
      prostheses were placed in 214 patients and had a mean service life of 51.7 months
      +/- 19.5 months standard deviation, with a range of 13.2 to 141.6 months. Of 14
      failed prostheses, 12 debonded, resulting in a success rate of 94.8 percent and
      clinical retention rate of 95.5 percent. No discernable rotation or drifting of
      the abutments was apparent in any of the prostheses. Overall patient satisfaction
      with RBFPDs was good, with an average assessment score of 8.5. CONCLUSIONS: The
      authors observed a 95.5 percent clinical retention rate of 269 two-unit RBFPDs,
      with no apparent drifting of the abutments. Longer-term follow-up studies are
      required. CLINICAL IMPLICATIONS: Two-unit RBFPDs are conservative and clinically
      retentive prostheses in the short to medium term.

PMID- 16803808
TI  - Motivating mothers to prevent caries: confirming the beneficial effect of
      counseling.
AB  - BACKGROUND: The purpose of this study was to compare the effect of a motivational
      interviewing (MI) counseling visit with traditional health education for mothers
      of young children at high risk of developing dental caries. METHODS: The authors
      enrolled 240 infants aged 6 to 18 months and their mothers in the study and
      randomly assigned them to MI or traditional health education (control) groups.
      Mothers in the control group received a pamphlet and watched a videotape. Those
      in the MI group received the pamphlet and watched the videotape, as well as
      received an MI counseling session and six follow-up telephone calls during the
      first year. There were no interventions in year 2. RESULTS: After two years,
      children in the MI group exhibited significantly less new caries (decayed or
      filled surfaces) than those in the control group (that is, a protective effect of
      MI) (odds ratio = 0.35, 95 percent confidence interval = 0.15 to 0.83).
      CONCLUSIONS: MI is a promising approach that warrants further attention in a
      variety of dental contexts. CLINICAL IMPLICATIONS: The results of this study show
      that MI has a protective effect with regard to the development of early childhood
      caries. One reason for this clinical effect is greater compliance with
      recommended fluoride varnish treatment regimens in families who received MI
      counseling compared with families who received traditional education.

PMID- 16803809
TI  - Two new clinical/laboratory protocols for CAD/CAM implant restorations.
AB  - BACKGROUND: Conventional casting technology has some disadvantages for dental
      laboratory technicians and restorative dentists, including porosity of
      restorations, miscasting and inaccuracy. It also is labor-intensive. Computer
      aided design/computer-aided manufacturing (CAD/CAM) technology was developed in
      the late 1980s for dentistry, and it significantly reduced and/or eliminated
      problems associated with dental castings. The purpose of this article is to give
      readers an overview of the use of CAD/CAM technology for dental implants and
      illustrate two clinical protocols for that use. CLINICAL IMPLICATIONS: The
      CAD/CAM technology described in this article can reduce restorative dentists'
      chairside time associated with implant treatment in both edentulous and partially
      edentulous patients, can decrease costs without sacrificing accuracy or
      biocompatibility for both clinicians and dental laboratory technicians, and is
      available to dental laboratories without the capital expenses associated with
      purchasing new technology.

PMID- 16803810
TI  - The differences between dental and medical care: implications for dental benefit
      plan design.
AB  - BACKGROUND: Dental benefit plans have grown since they were introduced in the
      1960s. More than one-half of the American population is covered by a private
      dental benefit plan today. In general, these plans have been designed to mirror
      medical insurance plans, despite the fact that dental care is significantly
      different from medical care. The author discusses the differences and how they
      should influence dental benefit plan design. CONCLUSIONS: The differences between
      dental care and medical care, how oral diseases are treated, the diseases'
      natural histories without treatment and the organization of the dental profession
      compared with that of the medical profession require that dental benefit plans be
      designed differently than medical insurance plans if they are to be effective.
      The operation of dental and medical plans requires different mind-sets.
      IMPLICATIONS: If they are to be effective, dental benefit plans and attempts to
      control the costs of those plans must be designed with the specific nature of
      oral diseases and the organization of the dental profession in mind.

PMID- 16803811
TI  - Dental safety net: current capacity and potential for expansion.
AB  - OBJECTIVES: The authors' objectives were to determine the size and
      characteristics of the dentally underserved U.S. population, describe the
      capacity of the safety net system to treat the underserved, explore policy
      options for expanding the system and discuss the policy implications of these
      findings. METHODS: The data came from published reports from health care
      organizations and researchers, as well as from public officials, dental educators
      and clinic directors. The values presented are estimates from available data.
      RESULTS: The underserved population consists of 82 million people from low-income
      families. Only 27.8 percent of this population visits a dentist each year. The
      primary components of the safety net are dental clinics in community health
      centers, hospitals, public schools and dental schools. This system has the
      capacity to care for about 7 to 8 million people annually. The politically
      feasible options for expanding the system include increasing the number of
      community clinics and their efficiency, requiring dental school graduates to
      receive one year of residency training, and requiring senior dental students and
      residents to work 60 days in community clinics and practices. This could increase
      the capacity of the system to treat about 10 million people annually. CONCLUSIONS
      AND CLINICAL IMPLICATIONS: The safety net system has limited capacity but could
      be improved to care for another 2.5 million people. Even if it is expanded,
      however, the majority of low-income patients would need to obtain care in private
      practices to reduce access disparities. The biggest challenge is convincing the
      American people to provide the funds needed to care for the poor in safety net
      clinics and private practices.

PMID- 16803812
TI  - Has the 'total-etch' concept disappeared?

PMID- 16803813
TI  - How to build a better team.

PMID- 16803814
TI  - May I market and sell dental devices?

PMID- 16803815
TI  - For the dental patient: dental care while traveling.

PMID- 16803816
TI  - Dental education: an evolving challenge.

PMID- 16803817
TI  - Dealing with disasters.

PMID- 16803818
TI  - Oral sedation.

PMID- 16803819
TI  - Where is Dr. Dawson?

PMID- 16803820
TI  - Orthodontics.

PMID- 16803821
TI  - What is a health degree?

PMID- 16803822
TI  - The use of adult stem cells in rebuilding the human face.
AB  - BACKGROUND: Stem cells have been isolated from a variety of embryonic and
      postnatal (adult) tissues, including bone marrow. Bone marrow stromal cells
      (BMSCs), which are non-blood-forming cells in marrow, contain a subset of
      skeletal stem cells (SSCs) that are able to regenerate all types of skeletal
      tissue: bone, cartilage, blood-supportive stromal cells and marrow fat cells.
      METHODS: Bone marrow suspensions are placed into culture for analysis of their
      biological character and for expansion of their number. The resulting populations
      of cells are used in a variety of assays to establish the existence of an adult
      SSC, and the ability of BMSC populations to regenerate hard tissues in the
      craniofacial region, in conjunction with appropriate scaffolds. RESULTS: Single
      cell analysis established the existence of a true adult SSC in bone marrow.
      Populations of ex vivo expanded BMSCs (a subset of which are SSCs) are able to
      regenerate a bone/marrow organ. In conjunction with appropriate scaffolds, these
      cells can be used to regenerate bone in a variety of applications. CONCLUSIONS:
      BMSCs have the potential to re-create tissues of the craniofacial region to
      restore normal structure and function in reconstructing the hard tissues of a
      face. Ex vivo expanded BMSCs with scaffolds have been used in a limited number of
      patients to date, but likely will be used more extensively in the near future.

PMID- 16803823
TI  - Endodontic or dental implant therapy: the factors affecting treatment planning.
AB  - BACKGROUND: Clinicians are confronted with difficult choices regarding whether a
      tooth with pulpal and/or periapical disease should be saved through endodontic
      treatment or be extracted and replaced with an implant. METHODS: The authors
      examined publications (research, literature reviews and systematic reviews)
      related to the factors affecting decision making for patients who have oral
      diseases or traumatic injuries. RESULTS: The factors to be considered included
      patient-related issues (systemic and oral health, as well as comfort and
      treatment perceptions), tooth- and periodontium-related factors (pulpal and
      periodontal conditions, color characteristics of the teeth, quantity and quality
      of bone, and soft-tissue anatomy) and treatment-related factors (the potential
      for procedural complications, required adjunctive procedures and treatment
      outcomes). CONCLUSIONS: On the basis of survival rates, it appears that more than
      95 percent of dental implants and teeth that have undergone endodontic treatment
      remain functional over time. CLINICAL IMPLICATIONS: Clinicians need to consider
      carefully several factors before choosing whether to perform endodontic therapy
      or extract a tooth and place an implant. The result should be high levels of
      comfort, function, longevity and esthetics for patients.

PMID- 16803824
TI  - The effect of periodontal surgery on bite force, occlusal contact area and bite
      pressure.
AB  - BACKGROUND: Tooth mobility resulting from the loss of periodontal support or
      trauma induced by periodontal surgery may change the amount of bite force (BF)
      and bite pressure (BP) and number of occlusal contact areas (OCAs). The aim of
      the authors' study was to compare BF, BP and OCA of teeth with periodontal
      disease before and after periodontal surgery with similar values of healthy
      teeth. METHODS: The authors performed quantitative analysis of BF, BP and OCA
      using a pressure measurement film. Ten patients with periodontitis who needed
      periodontal surgery served as the test group. The authors took measurements of
      BF, BP, OCA and mobility (using Miller's Mobility Index) just before surgery and
      at one, four and 12 weeks after surgery. They also measured clinical attachment
      levels (CAL) before surgery and 12 weeks after surgery. Ten subjects without
      periodontitis served as the control group. RESULTS: Although BF and OCA increased
      the first week after periodontal surgery, analysis of variance (ANOVA) showed no
      statistically significant differences at a 95 percent confidence interval. There
      were statistically significant differences between first-week mobility and that
      at four and 12 weeks (P = .001). A factorial ANOVA showed significant interaction
      between BF and mobility (P < .05). CONCLUSIONS: The authors' findings suggest
      that changes in BF, BP and OCA were not affected by periodontal surgery. However,
      mean mobility values and BF are correlated. Further investigations of this
      measurement method involving larger study populations and a longer follow-up
      period are needed. CLINICAL IMPLICATIONS: It seems to be helpful to follow
      occlusal changes after periodontal surgery using a pressure measurement film. It
      also may be suggested that this measurement method could be used to evaluate the
      treatment prognosis.

PMID- 16803825
TI  - An unusual pattern of dental damage with salivary gland aplasia.
AB  - BACKGROUND: Dental destruction can develop from numerous causes. Major salivary
      gland aplasia is an uncommon causative factor. The resulting xerostomia can lead
      to extensive dental demineralization. CASE DESCRIPTION: The author examined a 19
      year-old man because of the patient's concern regarding decreased salivary volume
      and his dental condition. There was extensive loss of tooth structure and an
      astonishing pattern of dental destruction most notable on the palatal portions of
      the maxillary molars and premolars that is best described as "chipping." It was
      only after taking the patient's history, clinically examining the patient and
      conducting a radioisotope study that the author was able to make a confident
      diagnosis of the absence of four major salivary glands. CLINICAL IMPLICATIONS:
      Dentists should be aware that salivary gland aplasia is an uncommon cause of
      dental deterioration. It may manifest itself not by extensive caries but by a
      dental chipping effect. Early recognition and a therapeutic strategy can prevent
      progressive dental damage.

PMID- 16803826
TI  - Managing dentin hypersensitivity.
AB  - BACKGROUND: The objective of this review is to inform practitioners about dentin
      hypersensitivity (DH) and its management. This clinical information is described
      in the context of the underlying biology. TYPES OF STUDIES REVIEWED: The authors
      used MEDLINE to find relevant English-language literature published in the period
      1999 to 2005. They used combinations of the search terms "dentin*," "tooth,"
      "teeth," "hypersensit*," "desensiti*" and "desensitiz*." They read abstracts and
      then full articles to identify studies describing etiology, prevalence, clinical
      features, controlled clinical trials of treatments and relevant laboratory
      research on mechanisms of action. RESULTS: The prevalence of DH varies widely,
      depending on the mode of investigation. Potassium-containing toothpastes are the
      most widely used at-home treatments. Most in-office treatments employ some form
      of "barrier," either a topical solution or gel or an adhesive restorative
      material. The reported efficacy of these treatments varies, with some having no
      better efficacy than the control treatments. Possible reasons for this
      variability are discussed. A flowchart summarizes the various treatment
      strategies. CLINICAL IMPLICATIONS: DH is diagnosed after elimination of other
      possible causes of the pain. Desensitizing treatment should be delivered
      systematically, beginning with prevention and at-home treatments. The latter may
      be supplemented with in-office modalities.

PMID- 16803827
TI  - Evaluating amalgam separators using an international standard.
AB  - BACKGROUND: Most amalgam particles generated during placement and removal of
      amalgam restorations are captured by chair-side traps and suction system traps
      and filters. Particles not captured can end up in the wastewater discharged from
      the dental office. Environmental initiatives to reduce the discharge of mercury
      containing products such as dental amalgam waste into the environment have
      sparked interest in the use of amalgam separators. METHODS: The authors used
      International Organization for Standardization (ISO) Standard 11,143 for Amalgam
      Separators in a laboratory test to evaluate the amalgam removal efficiency of 13
      commercially available amalgam separators and two commercially available
      filtration devices not marketed as amalgam separators but that have the potential
      to be used as such. RESULTS: All 13 amalgam separators and the two filtration
      devices exceeded the ISO Standard 11,143 requirement of 95 percent amalgam
      removal efficiency. The authors found statistical differences in the efficiency
      of the separators and filtration devices. No differences were found between the
      "empty" and "full" conditions for each separator. CONCLUSION AND CLINICAL
      IMPLICATIONS: This laboratory evaluation shows that amalgam separators and the
      filtration devices removed at least 97.05 percent of the amalgam in samples with
      particle-size distribution as specified in ISO Standard 11,143.

PMID- 16803828
TI  - An in vitro assessment of prefabricated fiber post systems.
AB  - BACKGROUND: The authors conducted a study to characterize the in vitro retention,
      fracture and light transmission behavior of four different fiber-reinforced resin
      based composite root canal posts. METHODS: The authors divided 44 teeth into four
      groups according to the type of post they would receive: parallel fiberglass
      posts, double-tapered fiber quartz posts, tapered fiberglass posts and two
      different types of parallel fiberglass posts. They prepared teeth and cemented
      posts with dual-cured resin cement. After the specimens aged, the authors
      conducted pull-out tests. For fracture testing, they loaded posts at 45 degrees
      in a universal testing machine. They determined load-to-fracture values and
      relative stiffness. They measured percentage of light transmission by means of a
      light microscope coupled with a spectrometer. RESULTS: Both tapered posts showed
      lower retention than did the parallel posts. Scanning electron microscropic
      analysis indicated that more cement adhered to the surfaces of the parallel
      fiberglass post than to those of the tapered fiberglass post. All posts
      demonstrated some plastic behavior, with the double-tapered fiber quartz post
      being stiffer than the others. CONCLUSION: Parallel fiber-reinforced composite
      posts showed better retention than did tapered posts when a dual-cured resin
      based cement was used. Translucent prefabricated posts have limited light
      transmission. CLINICAL IMPLICATIONS: Parallel prefabricated fiber posts luted
      with dual-cured resin-based cement seem to be suitable for clinical application
      in endodontically treated teeth that require post-and-core restoration, showing
      good retention and acceptable fracture resistance.

PMID- 16803829
TI  - Treating cervical dentin hypersensitivity with fluoride varnish: a randomized
      clinical study.
AB  - BACKGROUND: This subject-blind randomized clinical trial tested the efficacy of a
      new 5 percent sodium fluoride varnish (AllSolutions Fluoride Varnish, Dentsply
      Professional, York, Pa.) for treatment of cervical dentin hypersensitivity. The
      authors also compared the test varnish with a control fluoride varnish (Duraphat,
      Colgate Oral Pharmaceuticals, New York City). METHODS: The study involved
      application of the test or control varnish to 19 subjects (59 teeth) with tooth
      sensitivity. The authors applied each product once to each tooth, following
      manufacturers' instructions. They used a visual analog scale (VAS) to assess
      subjects' responses to compressed air and ice stimuli at six weeks before
      baseline, at baseline and at two, eight and 24 weeks after treatment. RESULTS:
      Mean VAS scores for teeth receiving the test varnish dropped from 34.9 (air) and
      68.0 (ice) at baseline to 26.3 (air) and 54.7 (ice) at two weeks after treatment.
      Mean scores at 24 weeks were 20.6 (air) and 34.8 (ice), representing
      statistically significant differences from baseline values. For the control
      varnish, mean VAS scores dropped from 36.9 (air) and 64.2 (ice) at baseline to
      32.9 (air) and 47.2 (ice) at two weeks, and to 20.8 (air) and 40.3 (ice) at 24
      weeks. The authors analyzed the data for statistical significance, accounting for
      clustering of teeth within subjects. CONCLUSION AND CLINICAL IMPLICATIONS: The
      test varnish was effective in reducing cervical dentin hypersensitivity. However,
      the efficacy was not significantly different from that of the control varnish.

PMID- 16803830
TI  - Overcoming the challenges of Class II resin-based composites.

PMID- 16803831
TI  - Assessing and correcting dental fees: an essential for the health of the dental
      practice.

PMID- 16803832
TI  - May I ethically treat the child of a friend who may not have custodial rights?

PMID- 16803833
TI  - Bisphosphonate medications and your oral health.

PMID- 16803834
TI  - Rate of progression determines the clinical outcome after neural transplantation
      in Parkinson's disease.

PMID- 16803835
TI  - Pes cavus pathogenesis in Charcot-Marie-Tooth disease type 1A.

PMID- 16803837
TI  - Orbitofrontal cortex hypometabolism, medication overuse headache, substance abuse
      and migraine: key pathophysiological issues.

PMID- 16803839
TI  - A polymorphic polymerase.

PMID- 16803840
TI  - One-year follow-up in a prospective, randomized study comparing radiofrequency
      and cryoablation of arrhythmias in Koch's triangle: clinical symptoms and event
      recording.
AB  - AIMS: To rely solely on clinical symptoms of recurrent palpitations to evaluate
      the success of interventional procedures can be misleading. This study was
      designed to assess the efficacy of event recording in evaluating long-term
      success in patients treated for atrioventricular nodal reentrant tachycardia
      (AVNRT) or right posteroseptally located accessory pathways (RPS) either by
      radiofrequency (RF) or by cryoablation (CA). METHODS AND RESULTS: Sixty-three
      patients with AVNRT and eight with RPS were randomized. Patients were encouraged
      to activate an event recorder in the case of recurrent palpitations for the first
      3 months. One year after the procedure, patients were asked specific arrhythmia
      related questions. Thirty-six patients underwent RF and 35 CA. Acute success was
      finally achieved in 34 (94%) patients in the RF and 33 (94%) in the CA groups.
      Assessment of long-term success demonstrated a similar proportion of palpitations
      in the RF and CA groups: 11 (31%) vs. 17 (49%). Only 12 patients activated the
      event recorder, four patients in RF, including one patient with chest pain, and
      eight in the CA group. Analysis of recordings revealed recurrent AVNRT or circus
      movement tachycardia in four patients (one RF and three CA), atrial fibrillation
      in one RF patient, and sinus tachycardia in six (one RF and five with CA). In
      addition, a complete 12 lead ECG of a recurrent arrhythmia was made in three RF
      and two CA patients (in-hospital or after the event recording). A total of seven
      patients underwent a second procedure (four RF and three CA). Without the event
      recorder, seven patients would have been misclassified as having recurrent
      arrhythmia. CONCLUSION: Event recording enhances the sensitivity of detecting
      arrhythmia recurrences in evaluating therapy efficacy and should be considered in
      every interventional follow-up study. Analysis of recordings showed that CA is as
      effective as RF in the treatment of AVNRT and RPS at long-term follow-up.

PMID- 16803842
TI  - Patterns of care study for postmastectomy radiotherapy in Japan: its role in
      monitoring the patterns of changes in practice.
AB  - BACKGROUND: Three prospective randomized clinical trials (RCT) in the 1990s
      demonstrated the survival benefit of postmastectomy radiotherapy (PMRT) for
      patients with locally advanced breast cancer. The present study was performed to
      evaluate whether the Patterns of Care Study (PCS) fulfills a role in monitoring
      the patterns of changes in clinical practices in Japan. METHODS: The first survey
      (JPCS-1) involved 79 Japanese facilities by two-stage cluster sampling of
      facilities and patients, and was carried out during 1998-2000. JPCS-1 included
      1124 patients with breast cancer who were treated between 1995 and 1997. The
      second survey (JPCS-2) was carried out during 2001-2003, involving 827 patients
      who were treated between 1999 and 2001 in 76 facilities. RESULTS: Patients with
      adverse risk factors, including pathologically axillary positive nodes (> or =4)
      and/or advanced primary disease (pT3-4) accounted for 57% of the patients who
      received PMRT in JPCS-1 and 72% of those in JPCS-2 (P = 0.039). The multiple
      radiotherapy target volume including the chest wall and regional lymph nodes was
      applied in 18% of the patients in JPCS-1 and 44% of those in JPCS-2 (P < 0.001).
      However, the dose distribution was calculated in only 42% of the patients in both
      surveys (P = 0.467). CONCLUSIONS: The eligibility and the target volume for PMRT
      were influenced by the outcome of RCT, but the quality of radiotherapy did not
      improve sufficiently. The PCS survey is useful to monitor the changes in patterns
      of clinical practice and can clarify some problems with radiotherapy techniques.

PMID- 16803841
TI  - Different responses to gefitinib in lung adenocarcinoma coexpressing mutant- and
      wild-type epidermal growth factor receptor genes.
AB  - Response to gefitinib is strongly associated with the status of the epidermal
      growth factor receptor gene. Here we report the different treatment responses in
      a case of lung adenocarcinoma coexpressing mutant-type gene in the primary lung
      mass and a wild-type gene in the metastatic bone lesions. This case demonstrated
      that at least two strains of tumor cells were present in a single patient. This
      may be one of the mechanisms of gefitinib resistance.

PMID- 16803843
TI  - Eight year experience with Studer ileal neobladder.
AB  - BACKGROUND: We reviewed our experience with orthotopic continent urinary
      reconstruction after radical cystectomy to assess the feasibility of Studer ileal
      neobladder for patients who are relatively advanced in age. METHODS: Between June
      1997 and January 2005, 31 consecutive male patients (mean age: 64 years)
      underwent lower urinary tract reconstruction after radical cystoprostatectomy.
      Perioperative and late complications, functional outcome of the neobladder,
      urinary continence, upper urinary tract status and renal function with the
      metabolic balance were evaluated in all patients. RESULTS: There was no
      perioperative death, and perioperative and late complication rates were 22.8% and
      3.3%, respectively. All 31 patients were able to void urine. Although the mean
      maximal functional capacity of the neobladder was 122 ml at 1 month after
      surgery, the mean capacities were increased to 247 ml at 6 months and 321 ml at 1
      year after the operation. Urodynamic results at 3 years showed unchanged
      characteristics as to micturition pattern and volume of residual urine and
      neobladder pressure remained low. Of 31 patients, 29 (93.5%) showed excellent or
      good continent status during the daytime and 9 (29%) were completely dry at night
      in 6 months after surgery. Even at 3 years after the operation, only 1 patient
      out of 21 evaluated required single pad during nighttime. In a subgroup of five
      patients (24%) older than 70 years, the status of continence was satisfactory at
      3 years after the reconstruction, and only one patient required a pad during the
      night at that point. Renal function levels and metabolic status were comparable
      before surgery and 3 years after surgery. Moreover, pyelography revealed normal
      condition of the upper urinary tract 1 month postoperatively in almost all cases.
      CONCLUSIONS: These data provide evidence that Studer ileal neobladder is a
      satisfactory surgical technique for selected patients at our institute. Even for
      patients older than 70 years, this urinary diversion procedure is safe in terms
      of morbidity and efficacious as indicated by functional outcome.

PMID- 16803844
TI  - A randomized phase III trial of postoperative adjuvant therapy with S-1 alone
      versus S-1 plus PSK for stage II/IIIA gastric cancer: Hokuriku-Kinki Immunochemo
      Therapy Study Group-Gastric Cancer (HKIT-GC).
AB  - In this randomized multicenter Phase III study, patients with curatively resected
      Stage II/IIIA gastric cancer were assigned to postoperative adjuvant therapy with
      an oral fluoropyrimidine S-1 alone (2 weeks of treatment and 1 week of rest for 6
      months, followed by 2 weeks of treatment and 2 weeks of rest for 6 months) or S-1
      combined with an oral biological response modifier PSK (the same regimen of S-1
      plus daily PSK for 12 months). The main objective was to evaluate the survival
      benefit and quality of life (QOL) of combined therapy. The primary end points
      were the time to relapse and the duration of survival after surgery, i.e. the
      rates of disease-free survival and overall survival at 3 and 5 years. The
      secondary end points were the relations of survival rates to drug compliance,
      QOL, adverse events, postoperative complications, relapse status, and the
      preoperative expression of immune or tumor markers. The sample size was 140 per
      treatment arm.

PMID- 16803846
TI  - Annual Medicago: from a model crop challenged by a spectrum of necrotrophic
      pathogens to a model plant to explore the nature of disease resistance.
AB  - BACKGROUND: Annual Medicago spp., including M. truncatula, play an important
      agronomic role in dryland farming regions of the world where they are often an
      integral component of cropping systems, particularly in regions with a
      Mediterranean or Mediterranean-type climate where they grow as winter annuals
      that provide both nitrogen and disease breaks for rotational crops. Necrotrophic
      foliar and soil-borne pathogens dominate these regions and challenge the
      productivity of annual Medicago and crop legume species. SCOPE: This review
      outlines some of the major and/or widespread diseases these necrotrophic
      pathogens cause on Medicago spp. It then explores the potential for using the
      spectrum of necrotrophic pathogen-host interactions, with annual Medicago as the
      host plant, to better understand and model pathosystems within the diseases
      caused by nectrotrophic pathogens across forage and grain legume crops.
      CONCLUSIONS: Host resistance clearly offers the best strategy for cost-effective,
      long-term control of necrotrophic foliar and soil-borne pathogens, particularly
      as useful resistance to a number of these diseases has been identified. Recently
      and initially, the annual M. truncatula has emerged as a more appropriate and
      agronomically relevant substitute to Arabidopsis thaliana as a model plant for
      legumes, and is proving an excellent model to understand the mechanisms of
      resistance both to individual pathogens and more generally to most forage and
      grain legume necrotrophic pathogens.

PMID- 16803845
TI  - Glu346Lys polymorphism in the methyl-CpG binding domain 4 gene and the risk of
      primary lung cancer.
AB  - BACKGROUND: Methyl-CpG binding domain 4 (MBD4) protein functions as a DNA repair
      enzyme and minimizes mutations at 5-methylcytosine. Polymorphisms in the DNA
      repair gene MBD4 may be associated with differences in DNA repair capacity and
      thereby influence an individual's susceptibility to lung cancer. To test this
      hypothesis, we examined the potential association between the MBD4 Glu346Lys
      polymorphism and the risk of lung cancer in a Korean population. METHODS: The
      MBD4 Glu346Lys genotypes were determined in 432 lung cancer patients and 432
      healthy age- and gender-matched control subjects. RESULTS: The distribution of
      the MBD4 Glu346Lys genotypes was not significantly different between the overall
      lung cancer cases and the controls. However, when the cases were categorized by
      tumor histology, the Lys346Lys genotype was associated with a significantly
      decreased risk of adenocarcinoma (AC) as compared with the Glu346Glu genotype
      [adjusted odds ratio (OR) = 0.50, 95% confidence interval (CI) = 0.26-0.97, P =
      0.04]. On the stratification analysis, the protective effect of the Lys346Lys
      genotype against AC was statistically significant in older individuals and
      heavier smokers (adjusted OR = 0.08, 95% CI = 0.01-0.64, P = 0.02; and adjusted
      OR = 0.09, 95% CI = 0.01-0.72, P = 0.02, respectively). CONCLUSIONS: Our findings
      suggest that the MBD4 Glu346Lys polymorphism could be used as a marker for
      genetic susceptibility to AC of the lung.

PMID- 16803847
TI  - Allozyme variation of populations of Castanopsis carlesii (Fagaceae) revealing
      the diversity centres and areas of the greatest divergence in Taiwan.
AB  - BACKGROUND AND AIMS: The genetic variation and divergence estimated by allozyme
      analysis were used to reveal the evolutionary history of Castanopsis carlesii in
      Taiwan. Two major questions were discussed concerning evolutionary issues: where
      are the diversity centres, and where are the most genetically divergent sites in
      Taiwan? METHODS: Twenty-two populations of C. carlesii were sampled throughout
      Taiwan. Starch gel electrophoresis was used to assay allozyme variation. Genetic
      parameters and mean FST values of each population were analysed using the BIOSYS
      2 program. Mean F(ST) values of each population against the remaining
      populations, considered as genetic divergence, were estimated using the FSTAT
      program. KEY RESULTS: Average values of genetic parameters describing the within
      population variation, the average number of alleles per locus (A=2.5), the
      effective number of alleles per locus (Ae=1.38), the allelic richness (Ar=2.38),
      the percentage of polymorphic loci (P=69%), and the expected heterozygosity
      (He=0.270) were estimated. High levels of genetic diversity were found for C.
      carlesii compared with other local plant species. Genetic differentiation between
      populations was generally low. CONCLUSIONS: From the data of expected
      heterozygosity, one major diversity centre was situated in central Taiwan
      corroborating previous reports for other plant species. According to the mean FST
      value of each population, the most divergent populations were situated in two
      places. One includes populations located in north central Taiwan between 24.80
      degrees N and 24.20 degrees N. The other is located in south-eastern Taiwan
      between 22.40 degrees N and 23.10 degrees N. These two regions are approximately
      convergent with the most divergent locations determined for several other plant
      species using chloroplast DNA markers published previously. An important finding
      obtained from this study is that unordered markers like allozymes can be used to
      infer past population histories as well as chloroplast DNA markers do.

PMID- 16803848
TI  - Phosphate (Pi) and arsenate uptake by two wheat (Triticum aestivum) cultivars and
      their doubled haploid lines.
AB  - BACKGROUND AND AIMS: Arsenic accumulation in cereal crops represents an important
      pathway for human exposure to arsenic from the environment. The objectives of the
      present work were to find whether the relationship between arsenate and phosphate
      (Pi) uptake rate differs among genotypes and to select genotypes with a low
      arsenate uptake rate with the aim of improving food safety and human health.
      METHODS: A hydroponic experiment was conducted using two wheat (Triticum
      aestivum) cultivars (Hanxuan 10 and Lumai 14) and ten doubled haploid (DH) lines
      derived from them to investigate Pi and arsenate uptake over 48 h. Ten plants
      were transferred to bottles containing 50 mL of pre-treatment solution containing
      0.5 mM CaCl2 and 5 mM MES set at pH 6.0 with 330 microM Pi as KH2PO4 and 7.33
      microM arsenate. The solutions were aerated continuously. At 8, 24 and 48 h after
      uptake, 1 mL of test solution was sampled for determination of Pi and arsenate
      concentrations. KEY RESULTS AND CONCLUSIONS: For each wheat line, Pi and arsenate
      concentrations in the test solution decreased with uptake time. Exponential (for
      Pi) or polynomial (for arsenate) regression plots fitted the data closely. For
      all genotypes, net Pi uptake rates decreased with time (from 0 to 48 h). However,
      net arsenate uptake rates decreased with time for D5, changed little with time
      for the male parent, D4 and D6, and increased with time for the others. An
      inflexion of about 25 microm Pi was observed for the relationship between
      arsenate and Pi concentrations in the test solution, indicating that 25 microm
      could be the point where the high-affinity uptake system 'switches on', or
      dominates over low-affinity uptake. In addition, the male parent, D1, D6 and D10
      were considered ideal genotypes because they possess Pi transporters that
      discriminate strongly against arsenate and are expected to accumulate less
      arsenate in the field.

PMID- 16803849
TI  - Variation in MLH1 distribution in recombination maps for individual chromosomes
      from human males.
AB  - Meiotic recombination is essential for the segregation of homologous chromosomes
      and the formation of normal haploid gametes. Little is known about patterns of
      meiotic recombination in human germ cells or the mechanisms that control these
      patterns. Documentation of the normal range of variability of recombination
      distribution over the genome among individuals is an essential prerequisite for
      understanding abnormal recombination patterns, which may be associated with non
      disjunction and chromosome rearrangements. In this article, variation in
      recombination maps for individual chromosomes among 10 normal human males is
      examined for the first time. An immunocytogenetic approach allowed analysis of
      pachytene cells, using antibodies to detect the mature synaptonemal complex
      (SCP1/SCP3), the centromere (CREST) and sites of crossing over (MLH1). Individual
      bivalents were identified with centromere-specific multicolor fluorescence in
      situ hybridization. Significant heterogeneity in MLH1 focus frequency across
      donors was observed for larger chromosome arms (P<0.05, one-way ANOVA).
      Significant inter-donor variation in the overall crossover frequency per cell was
      also found (P<0.0001, one-way ANOVA). Furthermore, several chromosome arms showed
      significant differences in crossover distribution along the SCs among donors.
      Inter-individual variation in interference distances was observed for all
      chromosomes. The significance of altered recombination patterns among individuals
      and the role of interference are discussed.

PMID- 16803850
TI  - Combination therapy with acipimox enhances the effect of growth hormone treatment
      on linear body growth in the normal and small-for-gestational-age rat.
AB  - Growth hormone (GH) therapy is often associated with adverse side effects,
      including impaired insulin sensitivity. GH treatment of children with idiopathic
      short stature does not lead to an optimized final adult height. It has been
      demonstrated that FFA reduction induced by pharmacological antilipolysis can
      stimulate GH secretion per se in both normal subjects and those with GH
      deficiency. However, to date, no investigation has been undertaken to establish
      efficacy of combination treatment with GH and FFA regulators on linear body
      growth. Using a model of maternal undernutrition in the rat to induce growth
      restricted offspring, we investigated the hypothesis that combination treatment
      with GH and FFA regulators can enhance linear body growth above that of GH alone.
      At postnatal day 28, male offspring of normally nourished mothers (controls) and
      offspring born with low birth weight [small for gestational age (SGA)] were
      treated with saline, GH, or GH (5 mg.kg(-1).day(-1)) in combination with acipimox
      (GH + acipimox, 20 mg.kg(-1).day(-1)) or fenofibrate (GH + fenofibrate, 30 mg.kg(
      1).day(-1)) for 40 days. GH plus acipimox treatment significantly enhanced linear
      body growth in the control and SGA animals above that of GH, as quantified by
      tibial and total body length. Treatment with GH significantly increased fasting
      plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA
      animals but was not significantly different between saline and GH-plus-acipimox
      treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment
      in both control and SGA animals, concomitant with a significant reduction in
      fasting plasma FFA and insulin concentrations. This is the first study to show
      that GH plus acipimox combination therapy, via pharmacological blocking of
      lipolysis during GH exposure, can significantly enhance the efficacy of GH in
      linear growth promotion and ameliorate unwanted metabolic side effects.

PMID- 16803851
TI  - Activation of dopamine D2 receptors simultaneously ameliorates various metabolic
      features of obese women.
AB  - The metabolic syndrome comprises a cluster of metabolic anomalies including
      insulin resistance, abdominal obesity, dyslipidemia, and hypertension. Previous
      studies suggest that impaired dopamine D2 receptor (D2R) signaling is involved in
      its pathogenesis. We studied the acute effects of bromocriptine (a D2R agonist)
      on energy metabolism in obese women; body weight and caloric intake remained
      constant. Eighteen healthy, obese women (BMI 33.2 +/- 0.6 kg/m(2), mean age 37.5
      +/- 1.7, range 22-51 yr) were studied twice in the follicular phase of their
      menstrual cycle in a prospective, single-blind, crossover design. Subjects
      received both placebo (P; always first occasion) and bromocriptine (B; always
      second occasion) on separate occasions for 8 days. At each occasion blood glucose
      and insulin were assessed every 10 min for 24 h, and circadian plasma free fatty
      acid (FFA) and triglyceride (TG) levels were measured hourly. Fuel oxidation was
      determined by indirect calorimetry. Body weight and composition were not affected
      by the drug. Mean 24-h blood glucose (P < 0.01) and insulin (P < 0.01) were
      significantly reduced by bromocriptine, whereas mean 24 h FFA levels were
      increased (P < 0.01), suggesting that lipolysis was stimulated. Bromocriptine
      increased oxygen consumption (P = 0.03) and resting energy expenditure (by 50
      kcal/day, P = 0.03). Systolic blood pressure was significantly reduced by
      bromocriptine. Thus these results imply that short-term bromocriptine treatment
      ameliorates various components of the metabolic syndrome while it shifts energy
      balance away from lipogenesis in obese humans.

PMID- 16803852
TI  - Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid
      insulin/IGF-I receptors in vascular smooth muscle cells.
AB  - Insulin and insulin-like growth factor I (IGF-I) are known to affect
      cardiovascular disease. We have investigated ligand binding and the dose-response
      relationship for insulin and IGF-I on vascular smooth muscle cells (VSMCs) at the
      receptor level. VSMCs from rat thoracic aorta were serum starved, stimulated with
      IGF-I or insulin, lysed, immunoprecipitated, and analyzed by Western blot. d-[U
      (14)C]Glucose accumulation and [6-(3)H]thymidine incorporation into DNA were also
      measured. Specific binding of both insulin and IGF-I was demonstrated, being
      higher for IGF-I. Both IGF-I receptor (IGF-IR) and insulin receptor (IR) beta
      subunits were detected and coprecipitated after immunoprecipitation (IP) against
      either of the two. No coprecipitation was found after reduction of disulphide
      bonds with dithiotreitol before IP. After stimulation with 10(-10)-10(-9) M IGF
      I, IP of the IGF-IR, or IR beta-subunit and immunoblot with anti-phosphotyrosine
      antibody, we found two distinct bands indicating phosphorylation of both the IGF
      IR and the IR beta-subunit. Stimulation with 10(-10)-10(-9) M insulin and IP
      against the IGF-IR did not show phosphorylation of either beta-subunit, whereas
      after IP of the IR we found phosphorylation of the IR beta-subunit.
      [(14)C]Glucose accumulation and [(3)H]thymidine incorporation were elevated in
      cells stimulated with IGF-I at 10(-10)-10(-7) M, reaching maximum by 10(-9) M.
      Insulin stimulation showed measurable effects only at supraphysiological
      concentrations, 10(-8)-10(-7) M. In conclusion, coprecipitation of both the IGF
      IR and the IR beta-subunit indicates the presence of hybrid insulin/IGF-I
      receptors in VSMC. At a physiological concentration, insulin activates the IR but
      does not affect either glucose metabolism or DNA synthesis, whereas IGF-I both
      activates the receptor and elicits biological effect.

PMID- 16803853
TI  - Hexose transporter mRNAs for GLUT4, GLUT5, and GLUT12 predominate in human
      muscle.
AB  - In the past few years, 8 additional members of the facilitative hexose
      transporter family have been identified, giving a total of 14 members of the
      SLC2A family of membrane-bound hexose transporters. To determine which of the new
      hexose transporters were expressed in muscle, mRNA concentrations of 11 glucose
      transporters (GLUTs) were quantified and compared. RNA from muscle from 10 normal
      volunteers was subjected to RT-PCR. Primers were designed that amplified 78- to
      241-base fragments, and cDNA standards were cloned for GLUT1, GLUT2, GLUT3,
      GLUT4, GLUT5, GLUT6, GLUT8, GLUT9, GLUT10, GLUT11, GLUT12, and GAPDH. Seven of
      these eleven hexose transporters were detectable in normal human muscle. The rank
      order was GLUT4, GLUT5, GLUT12, GLUT8, GLUT11, GLUT3, and GLUT1, with
      corresponding concentrations of 404 +/- 49, 131 +/- 14, 33 +/- 4, 5.5 +/- 0.5,
      4.1 +/- 0.4, 1.2 +/- .0.1, and 0.9 +/- 0.2 copies/ng RNA (means +/- SE),
      respectively, for the 10 subjects. Concentrations of mRNA for GLUT4, GLUT5, and
      GLUT12 were much higher than those for the remainder of the GLUTs and together
      accounted for 98% of the total GLUT isoform mRNA. Immunoblots of muscle
      homogenates verified that the respective proteins for GLUT4, GLUT5, and GLUT12
      were present in normal human muscle. Immunofluorescent studies demonstrated that
      GLUT4 and GLUT12 were predominantly expressed in type I oxidative fibers;
      however, GLUT5 was expressed predominantly in type II (white) fibers.

PMID- 16803854
TI  - Derangements in mitochondrial metabolism in intercostal and leg muscle of
      critically ill patients with sepsis-induced multiple organ failure.
AB  - Critically ill patients treated for multiple organ failure often develop muscle
      dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism
      are deranged in leg and intercostal muscle of critically ill patients with sepsis
      induced multiple organ failure. Ten critically ill patients suffering from sepsis
      induced multiple organ failure and requiring mechanical ventilation were included
      in the study. A group (n = 10) of metabolically healthy age- and sex-matched
      patients undergoing elective surgery were used as controls. Muscle biopsies were
      obtained from the vastus lateralis (leg) and intercostal muscle. The activities
      of citrate synthase and mitochondrial respiratory chain complexes I and IV and
      concentrations of ATP, creatine phosphate, and lactate were analyzed.
      Morphological evaluation of mitochondria was performed by electron microscopy.
      Activities of citrate synthase and complex I were 53 and 60% lower, respectively,
      in intercostal muscle of the patients but not in leg muscle compared with
      controls. The activity of complex IV was 30% lower in leg muscle but not in
      intercostal muscle. Concentrations of ATP and creatine phosphate were,
      respectively, 40 and 34% lower, and lactate concentrations were 43% higher in leg
      muscle but not in intercostal muscle. We conclude that both leg and intercostal
      muscle show a twofold decrease in mitochondrial content in intensive care unit
      patients with multiple organ failure, which is associated with lower
      concentrations of energy-rich phosphates and an increased anaerobic energy
      production in leg muscle but not in intercostal muscle.

PMID- 16803855
TI  - Role of Akt2 in contraction-stimulated cell signaling and glucose uptake in
      skeletal muscle.
AB  - The serine/threonine kinase Akt/PKB plays diverse roles in cells, and genetic
      studies have indicated distinct roles for the three Akt isoforms expressed in
      mammalian cells and tissues. Akt2 is a key signaling intermediate for insulin
      stimulated glucose uptake and glycogen synthesis in skeletal muscle. Akt2 has
      also been shown to be activated by exercise and muscle contraction in both
      rodents and humans. In this study, we used Akt2 knockout mice to explore the role
      of Akt2 in exercise-stimulated glucose uptake and glycogen synthesis as well as
      intracellular signaling pathways that regulate glycogen metabolism in skeletal
      muscle. We found that Akt2 deficiency does not affect basal or exercise
      stimulated glucose uptake or intracellular glycogen content in the soleus muscle.
      In addition, lack of Akt2 did not result in alterations in basal Akt Thr(308) or
      basal and contraction-stimulated glycogen synthase kinase-3beta (GSK-3beta)
      Ser(9) phosphorylation, glycogen synthase phosphorylation, or glycogen synthase
      activity. In contrast, in situ contraction failed to elicit normal increases in
      Akt T-loop Thr(308) phosphorylation and GSK-3alpha Ser(21) phosphorylation in
      tibialis anterior muscles from Akt2-deficient animals. Our data establish a key
      role for Akt2 in the regulation of GSK-3alpha Ser(21) phosphorylation with
      contraction and add genetic evidence to support the separation of the
      intracellular pathways regulated by insulin and exercise that converge on glucose
      uptake and glycogen synthesis in skeletal muscle.

PMID- 16803856
TI  - Sex-specific differences in leg fat uptake are revealed with a high-fat meal.
AB  - The mechanism(s) by which sex specific differences in regional body fat
      distribution develop are not known. We assessed the effects of a high-fat (HF)
      meal on fatty acid oxidation and uptake into regional fat depots using isotopic
      tracers and adipose biopsies. Thirty men (BMI 23.6 +/- 0.3 kg/m(2)) and 29 women
      (BMI 22.4 +/- 0.3 kg/m(2)) received a meal containing [(3)H]triolein. Twelve of
      the men and 13 of the women received an additional 80 g of triolein in the meal
      (HF) and the remainder received a normal-fat (NF) meal. Adipose tissue
      lipoprotein lipase (LPL) activity was measured in the fed and fasted state. After
      24 h, meal fatty acid uptake into subcutaneous adipose tissue was assessed. The
      efficiency of meal fat uptake into upper body subcutaneous fat was similar in
      both sexes, but women had a greater leg fat uptake, especially in response to a
      HF meal (P < 0.0001). A correlation between fed-state LPL activity and meal fat
      uptake was found in both upper and lower body fat (P < 0.0001, r = 0.69). These
      studies show that, in times of net fat storage, women preferentially increase
      uptake in leg adipose tissue, and this is likely mediated by fed-state LPL
      activity.

PMID- 16803857
TI  - Pioglitazone increases secretion of high-molecular-weight adiponectin from
      adipocytes.
AB  - Adiponectin is an adipocyte-derived serum protein that plays important roles in
      energy homeostasis, obesity, and insulin sensitivity. Using sucrose gradients and
      Western blotting of nondenaturing gels, we examined the adiponectin isoforms
      secreted from human adipose tissue, human and mouse adipocytes, and cell lines in
      response to pioglitazone added in vitro. The predominant form secreted from
      adipose tissue in vitro was the high-molecular-weight (HMW) isoform, with small
      amounts of low-molecular-weight (LMW) forms present. The addition of pioglitazone
      (1-3 micromM) in vitro increased the secretion of the HMW isoform, with no
      significant effect on the other isoforms. Human adipose tissue was also examined
      for changes in adiponectin mRNA levels upon pioglitazone treatment. No difference
      was detected, suggesting that the effect of pioglitazone is not at the
      transcriptional level but, rather, at a posttranscriptional phase of the
      secretory pathway. Additional experiments were conducted to determine whether
      adiponectin expression was mechanistically similar in other adipose cells.
      Examination of primary human adipocytes revealed an increase in intracellular HMW
      isoform with a decline in LMW forms following pioglitazone treatment, with a
      corresponding increase in the secreted HMW form. Similar results were observed
      with primary mouse adipocytes, 3T3-F422A cells, and SGBS human adipocyte cells,
      although differences in the distribution of HMW and LMW isoforms were apparent
      between cell types. Although there are differences in isoforms between species,
      in all cases pioglitazone served to increase the secretion of the HMW form of
      adiponectin.

PMID- 16803858
TI  - Trafficking of dietary fat in obesity-prone and obesity-resistant rats.
AB  - The trafficking of dietary fat was assessed in obesity-prone (OP) and obesity
      resistant (OR) male and female rats. Test meals containing [1-(14)C]palmitate
      were delivered through gastric feeding tubes while rats consumed a high
      carbohydrate diet (HCD) or after 5 days of a high-fat diet (HFD). Over the
      subsequent 24 h, the appearance of (14)C was followed in the GI tract, skeletal
      muscles (SM), liver, adipose tissues (AT), and expired CO(2). There was no
      difference in the production of (14)CO(2) between OP and OR rats consuming a HCD.
      However, after 5 days on HFD, OR rats produced significantly more (14)CO(2) after
      the test meal than OP rats (P < 0.001 females, P = 0.03 males). The differential
      oxidation of dietary fat between OP and OR rats on HFD was not due to differences
      in absorption but rather was associated with preferential disposition of tracer
      to AT in OP rats. Measurements of lipoprotein lipase in part explained increased
      tracer uptake by AT in OP rats but were not consistent with increased SM tracer
      uptake in OR rats. Surprisingly, female rats oxidized more tracer than male rats
      irrespective of phenotype or diet. These results are consistent with the notion
      that differences in the partitioning of dietary fat between storage in AT and
      oxidation in SM and liver that develop shortly after the introduction of a HFD
      may in part underlie the differential tendency for OR and OP rats to gain weight
      on this diet.

PMID- 16803859
TI  - Functional selectivity and classical concepts of quantitative pharmacology.
AB  - The concept of intrinsic efficacy has been enshrined in pharmacology for half of
      a century, yet recent data have revealed that many ligands can differentially
      activate signaling pathways mediated via a single G protein-coupled receptor in a
      manner that challenges the traditional definition of intrinsic efficacy. Some
      terms for this phenomenon include functional selectivity, agonist-directed
      trafficking, and biased agonism. At the extreme, functionally selective ligands
      may be both agonists and antagonists at different functions mediated by the same
      receptor. Data illustrating this phenomenon are presented from serotonin, opioid,
      dopamine, vasopressin, and adrenergic receptor systems. A variety of mechanisms
      may influence this apparently ubiquitous phenomenon. It may be initiated by
      differences in ligand-induced intermediate conformational states, as shown for
      the beta(2)-adrenergic receptor. Subsequent mechanisms that may play a role
      include diversity of G proteins, scaffolding and signaling partners, and receptor
      oligomers. Clearly, expanded research is needed to elucidate the proximal (e.g.,
      how functionally selective ligands cause conformational changes that initiate
      differential signaling), intermediate (mechanisms that translate conformation
      changes into differential signaling), and distal mechanisms (differential effects
      on target tissue or organism). Besides the heuristically interesting nature of
      functional selectivity, there is a clear impact on drug discovery, because this
      mechanism raises the possibility of selecting or designing novel ligands that
      differentially activate only a subset of functions of a single receptor, thereby
      optimizing therapeutic action. It also may be timely to revise classic concepts
      in quantitative pharmacology and relevant pharmacological conventions to
      incorporate these new concepts.

PMID- 16803860
TI  - Metabotropic glutamate 5 receptor antagonism is associated with antidepressant
      like effects in mice.
AB  - Antidepressant-like effects of metabotropic glutamate (mGlu)5 receptor
      antagonists have been reported previously. We now provide definitive
      identification of mGlu5 receptors as a target for these effects through the
      combined use of selective antagonists and mice with targeted deletion of the
      mGlu5 protein. In these experiments, the mGlu5 receptor antagonists 2-methyl-6
      (phenylethynyl)-pyridine (MPEP) and the more selective and metabolically stable
      analog 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) decreased
      immobility in the mouse forced swim test, a test predictive of antidepressant
      efficacy in humans. mGlu5 receptor knockout mice had a phenotype in the forced
      swim test that was congruent with the effects of receptor blockade; mGlu5
      receptor knockout mice were significantly less immobile than their wild-type
      counterparts. Consistent with mGlu5 receptor mediation of the antidepressant-like
      effects of MPEP, the effects of MPEP were not observed in mGlu5 receptor knockout
      mice, whereas comparable effects of the tricyclic antidepressant imiprimine
      remained active in the mutant mice. MPEP and imiprimine resulted in a synergistic
      antidepressant-like effect in the forced swim test. The drug interaction was not
      likely because of increased levels of drugs in the brain, suggesting a
      pharmacodynamic interaction of mGlu5 and monoaminergic systems in this effect.
      Thus, the present findings substantiate the hypothesis that mGlu5 receptor
      antagonism is associated with antidepressant-like effects. This mechanism may not
      only provide a novel approach to the therapeutic management of depressive
      disorders but also may be useful in the augmentation of effects of traditional
      antidepressant agents.

PMID- 16803861
TI  - Utilization of combined chemical modifications to enhance the blood-brain barrier
      permeability and pharmacological activity of endomorphin-1.
AB  - The endogenous mu-opioid receptor agonist, endomorphin (EM)-1, cannot be
      delivered into the central nervous system (CNS) in sufficient quantity to elicit
      analgesia when given systemically because it is severely restricted by the blood
      brain barrier (BBB). To improve the physicochemical characteristics of EM-1 and
      subsequently achieve greater BBB permeation, we synthesized a series of EM-1
      analogs by combining successful chemical modifications, including N-terminal
      cationization, C-terminal chloro-halogenation, and unnatural amino acid (d-Ala,
      Sar, and d-Pro-Gly) substitutions in position 2. Presently, their binding and
      bioassay activity, lipophilicity, stability, and antinociceptive activity were
      determined and compared. Guanidino-addition and chloro-halogenation attenuated
      the mu-receptor affinity to some extent, but they demonstrated differences in the
      influence on stability. It appeared that guanidino-addition contributed to brain
      stability enhancement for the greater part, whereas chloro-halogenation together
      with amino acid substitutions in position 2 was of more importance for the
      stability enhancement in serum than in brain. Determination of the octanol/buffer
      coefficient revealed that chloro-halogenation did compromise the decreased
      lipophilicity caused by guanidino-addition, and introduction of d-Ala as well as
      d-Pro-Gly, but not Sar, in place of l-Pro(2), also increased the overall
      lipophilicity to some extent. Among the peptides tested, intracerebroventricular
      injection of guanidino-[d-Ala(2), p-Cl-Phe(4)]EM-1 showed the strongest
      analgesia, being 3 times more potent than the parent peptide. We also found that
      in comparison with EM-1, the four d-Ala-containing tetrapeptides and the chloro
      halogenated d-Pro-Gly-containing pentapeptide elicited significant and prolonged
      central-mediated analgesia upon subcutaneous administration, indicating that more
      peptides reached the CNS, eliciting greater analgesic effect.

PMID- 16803862
TI  - Pharmacological characterization of cGMP regulation by the
      biarylpropylsulfonamide class of positive, allosteric modulators of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
AB  - The biarylpropylsulfonamide class of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) potentiators represented by N-2-(4-(4
      cyanophenol)phenol)propyl-2-propanesulfonamide (LY404187) and (R)-4'-[1-fluoro-1
      methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide
      (LY503430) are positive, allosteric AMPA receptor activators, which enhance AMPA
      receptor-mediated neurotransmission by reducing desensitization of the ion
      channel. Although these compounds have efficacy in in vivo rodent models of
      cognition, depression, and Parkinson's disease, little is known about biochemical
      pathways activated by these agents. Given the well established regulation of the
      nitric oxide/cGMP pathway by excitatory neurotransmission, the current study
      characterized AMPA receptor potentiator-mediated cGMP response in mouse
      cerebellum. Acute treatment by both LY404187 and LY503430 [2.0, 5.0, or 10 mg/kg
      subcutaneously (s.c.)] elevated basal cerebellar cGMP levels in a dose-dependent
      manner. Pretreatment with the noncompetitive, allosteric AMPA receptor-selective
      antagonist 7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine-7-carboxamide, 5-(4
      aminophenyl)-8,9-dihydro-N,8-dimethyl-monohydrochloride-(9CI) (GYKI 53655) [3.0
      mg/kg intraperitoneally (i.p.)], completely blocked the effect of LY404187,
      demonstrating that activation of AMPA receptors induces cGMP levels.
      Interestingly, pretreatment with the N-methyl-d-aspartate (NMDA) open channel
      blocker dizocilpine (0.3 and 1.0 mg/kg i.p.) also abolished the AMPA receptor
      potentiator-mediated cGMP accumulation, indicating that activation of AMPA
      receptors leads to NMDA receptor-mediated transmission involved in cGMP
      regulation. Pharmacological augmentation of the endogenous glutamate tone via the
      alkaloid harmaline (20-60 mg/kg i.p.) synergized with AMPA potentiator activity
      and provided further direct evidence of in vivo allosteric activation of AMPA
      receptors by LY404187. The synergism between harmaline and LY404187 was specific,
      since cGMP accumulation induced by foot-shock stress was not augmented by the
      AMPA receptor potentiator. Taken together, these data indicate that the cGMP
      system may play an important role in pharmacological efficacy of the
      biarylpropylsulfonamide class of AMPA receptor potentiators.

PMID- 16803863
TI  - Confirmation and fine mapping of ethanol sensitivity quantitative trait loci, and
      candidate gene testing in the LXS recombinant inbred mice.
AB  - In previous studies, we have mapped quantitative trait loci (QTLs) for hypnotic
      sensitivity to ethanol using a small recombinant inbred (RI) panel and a large
      F(2) backcross. Alcohol sensitivity is a major predictor of long-term risk for
      alcoholism. We remapped hypnotic sensitivity using a new set of 75 RI strains,
      the LXS, derived from Inbred Long Sleep and Inbred Short Sleep strains. We
      expected to improve mapping resolution in the QTL regions and to identify novel
      QTLs for loss of the righting reflex due to ethanol. We used three common mapping
      algorithms (R/qtl, QTL Cartographer, and WebQTL) to map QTLs in the LXS, and we
      compared the results. Most mapping studies use only a single algorithm, an
      approach that may result in failure to identify minor QTLs. We confirmed most of
      our previously reported QTLs, although one major QTL from earlier work (Lore2)
      failed to replicate, possibly because it represented multiple linked genes
      separated by recombination in the RI strains. We also report narrowed confidence
      intervals, based on mapping with a new genetic resource of more than 4000
      polymorphic single-nucleotide polymorphism markers. These narrowed confidence
      intervals will facilitate candidate gene identification and assessment of overlap
      with human regions specifying risk for alcoholism. Finally, we present an
      approach for using these RI strains to assess evidence for candidate genes in the
      narrowed intervals, and we apply this method to a strong candidate, the serotonin
      transporter.

PMID- 16803864
TI  - Orphan receptor small heterodimer partner is an important mediator of glucose
      homeostasis.
AB  - The orphan receptor small heterodimer partner (SHP; NROB2) is a transcriptional
      repressor that inhibits nuclear receptor signaling in diverse metabolic pathways.
      Here, we report that SHP(-/-) mice exhibited hypoinsulinemia with age, which was
      associated with increased peripheral insulin sensitivity and increased response
      of isolated islets to glucose stimulation, yet maintain normal levels of blood
      glucose. Deficiency in SHP function resulted in up-regulation of glucose
      transporter 4 mRNA and glucose uptake in muscles, and overexpression of SHP in
      C2C12 cells inhibited both basal and peroxisomal proliferator-activated receptor
      gamma (PPARgamma) coactivator-1alpha-stimulated glucose transporter 4 expression
      and glucose uptake. SHP(-/-) hepatocytes showed markedly decreased basal glucose
      production in cultures, and SHP(-/-) livers had increased glycogen stores and
      were more sensitive to insulin inhibition of glucose output, which were
      concomitant with decreased expression for PPARgamma1, fatty acid translocase,
      glucose-6-phosphatase, and phosphoenol/pyruvate carboxykinase, and increased
      mRNAs for glucokinase and pyruvate kinase. In white fat, SHP deficiency resulted
      in up-regulation of genes involved in insulin sensitizing, including PPARgamma2
      and adiponectin. We show that, at the transcriptional level, SHP directly
      represses adiponectin promoter activity by PPARgamma/liver receptor homolog-1.
      The results suggest that the increases in insulin sensitivity through multiple
      signaling pathways in muscle, liver, and fat, with an increase in islet secretory
      function, represent the complex mechanism whereby SHP deficiency leads to
      improvement in insulin sensitivity, secretion, and diabetes.

PMID- 16803865
TI  - A constitutively active mutant of the human lutropin receptor (hLHR-L457R)
      escapes lysosomal targeting and degradation.
AB  - Using biochemical and imaging approaches, we examined the postendocytotic fate of
      the complex formed by human choriogonadotropin (hCG) and a constitutively active
      mutant of the human lutropin receptor (hLHR-L457R) found in a boy with precocious
      puberty and Leydig cell hyperplasia. After internalization, some of the complex
      formed by the hLHR-wild type (hLHR-wt) and hCG recycles to the cell surface, and
      some is found in lysosomes where the hormone is degraded. In contrast, the
      complex formed by the hLHR-L457R and hCG is not routed to the lysosomes, most of
      it is recycled to the cell surface and hormone degradation is barely detectable.
      For both, hLHR-wt and -L457R, there is an hCG-induced loss of cell surface
      receptors that accompanies internalization but this loss cannot be prevented by
      leupeptin. The removal of recycling motifs of the hLHR by truncation of the C
      terminal tail at residue 682 greatly enhances the lysosomal accumulation of the
      hormone-receptor complexes formed by the hLHR-wt or the L457R mutant, the
      degradation of the internalized hormone, and the loss of cell surface receptors.
      The degradation of the hormone internalized by these mutants as well as the loss
      of cell surface receptors is largely prevented by leupeptin. These results
      highlight a previously unrecognized complexity in the postendocytotic trafficking
      of the hLHR and document a clear difference between the properties of the
      constitutively active mutant and the agonist-activated hLHR-wt. This lack of
      lysosomal degradation of the L457R mutant could contribute to its constitutive
      activity by prolonging the duration of signaling.

PMID- 16803866
TI  - Insulin-like growth factor-I induces alpha(1B)-adrenergic receptor
      phosphorylation through G beta gamma and epidermal growth factor receptor
      transactivation.
AB  - IGF-I induces alpha(1B)-adrenoceptor (alpha(1B)-AR) phosphorylation. The effect
      of IGF-I was rapid and transient, reaching near-maximal values at 10 min and
      decreasing after 30 min; it was observed at low IGF-I concentrations (EC(50)
      approximately 10 ng/ml) and was associated to receptor desensitization as
      evidenced by a decreased alpha(1B)-adrenergic effect on intracellular calcium and
      production of inositol phosphates. The effect of IGF-I was markedly decreased in
      cells treated with pertussis toxin suggesting involvement of pertussis toxin
      sensitive G proteins. Transfection of the carboxyl terminus of the beta
      adrenergic receptor kinase or the Deltap85 mutant of phosphoinositide 3-kinase
      (PI3K) markedly decreased the alpha(1B)-AR phosphorylation induced by IGF-I
      without decreasing the receptor phosphorylation induced by noradrenaline.
      Inhibitors of PI3K and protein kinase C blocked IGF-I-induced alpha(1B)-AR
      phosphorylation. In addition, it was observed that AG1478, an inhibitor of the
      epidermal growth factor (EGF) receptor kinase, and BB-94, a metalloproteinase
      inhibitor, also diminished IGF-I-induced adrenoceptor phosphorylation. The data
      clearly show that IGF-I triggers a complex signaling pathway, which leads to the
      phosphorylation and desensitization of a serpentine G protein-coupled receptor,
      suggesting the following hypothetical model: 1) stimulation of IGF-I receptors
      activate pertussis toxin-sensitive G proteins; 2) the growth factor action
      activates metalloproteinases, which catalyze heparin binding-EGF shedding, and
      transactivation of EGF receptors, and 3) dissociated Gbetagamma subunits and
      phosphotyrosine residues seem to trigger PI3K activity, which leads to activation
      of protein kinase C, resulting in alpha(1B)-AR phosphorylation and
      desensitization.

PMID- 16803867
TI  - In vivo imaging of hepatic growth hormone signaling.
AB  - We developed a system to noninvasively and repeatedly image in vivo hepatic GH
      signaling. GH regulates postnatal growth and metabolism. It affects numerous
      tissues, but has major effects in liver. We used nude mice for adenoviral
      mediated delivery of a signal transducer and activator of transcription 5
      dependent GH response element, a luciferase reporter to detect GH signaling
      pathway activation. We detected by noninvasive bioluminescence imaging GH-induced
      hepatic GH signaling serially within intact mice. Statistically significant
      effects of GH dose and time dependence were detected in the liver luciferase
      signal that peaked 3 h after GH injection. Codelivery of GH receptor
      significantly enhanced GH response, an effect that was further augmented by
      fasting. Our imaging system allows detailed in vivo analysis of GH signaling and
      action and may be a paradigm for studies of additional signaling pathways in
      liver and other tissues.

PMID- 16803868
TI  - Enigma interacts with adaptor protein with PH and SH2 domains to control insulin
      induced actin cytoskeleton remodeling and glucose transporter 4 translocation.
AB  - APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3
      kinase-independent pathway involved in insulin-stimulated glucose transport. We
      recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner
      of APS and showed that APS-Enigma complex plays a critical role in actin
      cytoskeleton organization in fibroblastic cells. Because actin rearrangement is
      important for insulin-induced glucose transporter 4 (Glut 4) translocation, we
      studied the potential involvement of Enigma in insulin-induced glucose transport
      in 3T3-L1 adipocytes. Enigma mRNA was expressed in differentiated adipocytes and
      APS and Enigma were colocalized with cortical actin. Expression of an APS mutant
      unable to bind Enigma increased the insulin-induced Glut 4 translocation to the
      plasma membrane. By contrast, overexpression of Enigma inhibited insulin
      stimulated glucose transport and Glut 4 translocation without alterations in
      proximal insulin signaling. This inhibitory effect was prevented with the
      deletion of the LIM domains of Enigma. Using time-lapse fluorescent microscopy of
      green fluorescent protein-actin, we demonstrated that the overexpression of
      Enigma altered insulin-induced actin rearrangements, whereas the expression of
      Enigma without its LIM domains was without effect. A physiological link between
      increased expression of Enigma and an alteration in insulin-induced glucose
      uptake was suggested by the increase in Enigma mRNA expression in adipose tissue
      of diabetic obese patients. Taken together, these data strongly suggest that the
      interaction between APS and Enigma is involved in insulin-induced Glut 4
      translocation by regulating cortical actin remodeling and raise the possibility
      that modification of APS/Enigma ratio could participate in the alteration of
      insulin-induced glucose uptake in adipose tissue.

PMID- 16803869
TI  - Influence of human Ect2 depletion and overexpression on cleavage furrow formation
      and abscission.
AB  - The guanine nucleotide-exchange factor (GEF) Ect2 is essential for cytokinesis.
      Here we studied the subcellular localization of Ect2 and examined the
      consequences of either depleting or overexpressing Ect2 in human cells. We show
      that in mitotic cells Ect2 localizes to the central spindle and to the cell
      cortex. The latter association is mediated through a PH domain in Ect2 and
      central spindle localization requires the MKlp1-MgcRacGAP and MKlp2-Aurora-B
      complexes. Ect2 directly interacts with MKlp1-MgcRacGAP through its BRCT domain,
      whereas MKlp2-Aurora-B probably exerts a regulatory role in Ect2 central spindle
      targeting. Depletion of Ect2 impaired cleavage furrow formation and RhoA and
      Citron kinase failed to accumulate at the cleavage furrow. Ect2 displacement from
      the central spindle revealed that physiological levels of this protein in this
      location are not crucial for RhoA activation and cytokinesis. In cells
      overexpressing appropriate N-terminal Ect2 fragments, RhoA and Citron kinase
      localized to the cleavage furrow and ingression occurred, but abscission failed.
      This failure could be correlated with the persistence of these fragments at
      structures surrounding the midbody, suggesting that abscission requires the
      displacement of Ect2 from the contractile ring and its re-import into the
      nucleus.

PMID- 16803870
TI  - Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2
      in mammalian hair cells.
AB  - The plasma membrane Ca2+-ATPase-2 (PMCA2) is expressed in stereocilia of hair
      cells of the inner ear, whereas PMCA1 is expressed in the basolateral plasma
      membrane of hair cells. Both extrude excess Ca2+ from the cytosol. They are
      predicted to contain ten membrane-spanning segments, two large cytoplasmic loops
      as well as cytosolic N- and C-termini. Several isoform variants are generated for
      both PMCA1 and PMCA2 by alternative splicing, affecting their first cytosolic
      loop (A-site) and their C-terminal tail. To understand how these isoforms are
      differentially targeted in hair cells, we investigated their targeting regions
      and expression in hair cells. Our results show that a Leu-Ile motif in 'b'-tail
      splice variants promotes PMCA1b and PMCA2b basolateral sorting in hair cells.
      Moreover, apical targeting of PMCA2 depends on the size of the A-site-spliced
      insert, suggesting that the conformation of the cytoplasmic loop plays a role in
      apical targeting.

PMID- 16803871
TI  - Initiation of cofilin activity in response to EGF is uncoupled from cofilin
      phosphorylation and dephosphorylation in carcinoma cells.
AB  - It has been demonstrated that the actin-severing activity of cofilin can be
      downregulated by LIM kinase (LIMK)-dependent phosphorylation at residue Ser3.
      Chemotactic stimulation in various cell types induces cofilin dephosphorylation,
      suggesting that cofilin activation in these cells occurs by a dephosphorylation
      mechanism. However, resting metastatic carcinoma cells have the majority of their
      cofilin in a dephosphorylated but largely inactive state. Stimulation with
      epidermal growth factor (EGF) induces an increase in cofilin activity after 60
      seconds together with an increase in phosphorylated cofilin (p-cofilin),
      indicating that cofilin dephosphorylation is not coupled to cofilin activation in
      these cells. Suppression of LIMK function by inhibiting Rho-associated protein
      kinase (ROCK) or LIMK siRNA inhibited the EGF-induced cofilin phosphorylation but
      had no effect on cofilin activity or cofilin-dependent lamellipod protrusion
      induced by EGF. Correlation analysis revealed that cofilin, p-cofilin and LIMK
      are not colocalized, and changes in the location of these proteins upon
      stimulation with EGF indicate that they are not functionally coupled.
      Phospholipase C, which has been implicated in cofilin activation following
      stimulation with EGF, does not regulate p-cofilin levels following stimulation
      with EGF. Therefore, our results do not support a model for the initial
      activation of cofilin by dephosphorylation in response to chemoattractant
      stimulation in metastatic carcinoma cells.

PMID- 16803872
TI  - NFAT3 is specifically required for TNF-alpha-induced cyclooxygenase-2 (COX-2)
      expression and transformation of Cl41 cells.
AB  - NFAT family is recognized as a transcription factor for inflammation regulation
      by inducing the expression of proinflammatory cytokines, such as tumor necrosis
      factor-alpha (TNF-alpha), the key mediator of inflammation, which was reported to
      induce cell transformation in mouse epidermal Cl41 cells. In this study, we
      demonstrated that TNF-alpha was able to induce NFAT activation, as well as the
      expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase
      (iNOS). The induction of COX-2 by TNF-alpha was abolished by knockdown of NFAT3
      with its siRNA, while the induction of iNOS was not effected. Moreover, TNF-alpha
      induced anchorage-independent cell growth was significantly inhibited by NFAT3
      siRNA and cyclosporine A, a chemical inhibitor for the calcineurin/NFAT pathway,
      which suggests the importance of NFAT3 in regulating TNF-alpha-induced anchorage
      independent cell growth. Consequently, impairment of COX-2 by its siRNA or
      selective inhibitor also inhibited TNF-alpha-induced anchorage-independent cell
      growth. Taken together, our results indicate that NFAT3 plays an important role
      in the regulation of TNF-alpha-induced anchorage-independent cell growth, at
      least partially, by inducing COX-2 expression in Cl41 cells. These findings
      suggest that NFAT3/cyclooxygenase-2 act as a link between inflammation and
      carcinogenesis by being involved in the tumor promotion stage.

PMID- 16803873
TI  - Thyroid hormone receptors TRalpha1 and TRbeta differentially regulate gene
      expression of Kcnq4 and prestin during final differentiation of outer hair cells.
AB  - Thyroid hormone (TH or T3) and TH-receptor beta (TRbeta) have been reported to be
      relevant for cochlear development and hearing function. Mutations in the TRbeta
      gene result in deafness associated with resistance to TH syndrome. The effect of
      TRalpha1 on neither hearing function nor cochlear T3 target genes has been
      described to date. It is also uncertain whether TRalpha1 and TRbeta can act
      simultaneously on different target genes within a single cell. We focused on two
      concomitantly expressed outer hair cell genes, the potassium channel Kcnq4 and
      the motor protein prestin Slc26a5. In outer hair cells, TH enhanced the
      expression of the prestin gene through TRbeta. Simultaneously Kcnq4 expression
      was activated in the same cells by derepression of TRalpha1 aporeceptors mediated
      by an identified THresponse element, which modulates KCNQ4 promoter activity. We
      show that T3 target genes can differ in their sensitivity to TH receptors having
      the ligand either bound (holoreceptors) or not bound (aporeceptors) within single
      cells, and suggest a role for TRalpha1 in final cell differentiation.

PMID- 16803874
TI  - Redox regulation of CD21 shedding involves signaling via PKC and indicates the
      formation of a juxtamembrane stalk.
AB  - Soluble CD21 (sCD21), released from the plasma membrane by proteolytic cleavage
      (shedding) of its extracellular domain (ectodomain) blocks B cell/follicular
      dendritic cell interaction and activates monocytes. We show here that both serine
      and metalloproteases are involved in CD21 shedding. Using the oxidant
      pervanadate to mimic B cell receptor activation and thiol antioxidants such as N
      acetylcysteine (NAC) and glutathione (GSH) we show that CD21 shedding is a redox
      regulated process inducible by oxidation presumably through activation of a
      tyrosine kinase-mediated signal pathway involving protein kinase C (PKC), and by
      reducing agents that either directly activate the metalloprotease and/or modify
      intramolecular disulfide bridges within CD21 and thereby facilitate access to the
      cleavage site. Lack of short consensus repeat 16 (SCR16) abolishes CD21 shedding,
      and opening of the disulfide bridge between cys-2 (Cys941) and cys-4 (Cys968) of
      SCR16 is a prerequisite for CD21 shedding. Replacing these cysteines with
      selenocysteines (thereby changing the redox potential from -180 to -381 mV)
      results in a loss of inducible CD21 shedding, and removing this bridge by
      exchanging these cysteines with methionines increases CD21 shedding.

PMID- 16803875
TI  - Wheat eukaryotic initiation factor 4B organizes assembly of RNA and eIFiso4G,
      eIF4A, and poly(A)-binding protein.
AB  - The eukaryotic translation initiation factor (eIF) 4B promotes the RNA-dependent
      ATP hydrolysis activity and ATP-dependent RNA helicase activity of eIF4A and
      eIF4F during translation initiation. Although this function is conserved among
      plants, animals, and yeast, eIF4B is one of the least conserved of initiation
      factors at the sequence level. To gain insight into its functional conservation,
      the organization of the functional domains of eIF4B from wheat has been
      investigated. Plant eIF4B contains three RNA binding domains, one more than
      reported for mammalian or yeast eIF4B, and each domain exhibits a preference for
      purine-rich RNA. In addition to a conserved RNA recognition motif and a C
      terminal RNA binding domain, wheat eIF4B contains a novel N-terminal RNA binding
      domain that requires a short, lysine-rich containing sequence. Both the lysine
      rich motif and an adjacent, C-proximal motif are conserved with an N-proximal
      sequence in human and yeast eIF4B. The C-proximal motif within the N-terminal RNA
      binding domain in wheat eIF4B is required for interaction with eIFiso4G, an
      interaction not reported for other eIF4B proteins. Moreover, each RNA binding
      domain requires dimerization for binding activity. Two binding sites for the
      poly(A)-binding protein were mapped to a region within each of two conserved 41
      amino acid repeat domains on either side of the C-terminal RNA binding domain.
      eIF4A bound to an adjacent region within each repeat, supporting a central role
      for these conserved eIF4B domains in facilitating interaction with other
      components of the translational machinery. These results support the notion that
      eIF4B functions by organizing multiple components of the translation initiation
      machinery and RNA.

PMID- 16803876
TI  - Assembly of the major light-harvesting chlorophyll-a/b complex: Thermodynamics
      and kinetics of neoxanthin binding.
AB  - The major light-harvesting chlorophyll-a/b complex in most higher plants contains
      three carotenoids, lutein, neoxanthin, and violaxanthin. How these pigments are
      assembled into the complex during its biogenesis is largely unknown. Here we show
      that neoxanthin but not lutein can dissociate from the fully assembled complex.
      Its equilibrium binding constant in a detergent system (0.1% n-dodecyl-beta-D
      maltoside) was determined to be > or = 10(6) m(-1). Neoxanthin insertion into
      light-harvesting chlorophyll-a/b complex prefolded from overexpressed apoprotein
      (Lhcb1*2 from Pisum sativum) in the presence of chlorophylls a, b, and lutein as
      the sole carotenoid is kinetically controlled by an activation energy barrier of
      approximately 120 kJ mol(-1). This is the first thermodynamic and kinetic
      description of a binding equilibrium between a non-covalently bound pigment of
      the photosynthetic apparatus and its protein complex. Dissociation of neoxanthin
      from the major light-harvesting chlorophyll-a/b complex upon temperature increase
      is discussed in terms of providing a readily available substrate pool for
      synthesizing abscisic acid as part of a heat and drought stress response.

PMID- 16803877
TI  - Untranslated regions of FbRbcS1 mRNA mediate bundle sheath cell-specific gene
      expression in leaves of a C4 plant.
AB  - C4 photosynthesis typically requires two specialized leaf cell types, bundle
      sheath (bs) and mesophyll (mp), which provide the foundation for this highly
      efficient carbon assimilation pathway. In leaves of Flaveria bidentis, a
      dicotyledonous C4 plant, ribulose 1,5-bisphosphate carboxylase (rubisco)
      accumulates only in bs cells surrounding the vascular centers and not in mp
      cells. This is in contrast to the more common C3 plants, which accumulate rubisco
      in all photosynthetic cells. Many previous studies have focused on
      transcriptional control of C4 cell type-specificity; however, post
      transcriptional regulation has also been implicated in the bs-specific expression
      of genes encoding the rubisco subunits. In this current study, a biolistic leaf
      transformation assay has provided direct evidence that the 5'- and 3'
      untranslated regions (UTRs) of F. bidentis FbRbcS1 mRNA (from a nuclear gene
      encoding the rubisco small subunit), in themselves, confer strong bs cell
      specific expression to gfpA reporter gene transcripts when transcribed from a
      constitutive CaMV promoter. In transformed leaf regions, strong bs cell-specific
      GFP expression was accompanied by corresponding bs cell-specific accumulation of
      the constitutively transcribed FbRbcS1 5'-UTR-gfpA-3'-UTR mRNAs. Control
      constructs lacking any RbcS mRNA sequences were expressed in all leaf cell types.
      These findings demonstrate that characteristic cell type-specific FbRbcS1
      expression patterns in C4 leaves can be established entirely by sequences
      contained within the transcribed UTRs of FbRbcS1 mRNAs. We conclude that
      selective transcript stabilization (in bs cells) or degradation (in mp cells)
      plays a key role in determining bs cell-specific localization of the rubisco
      enzyme.

PMID- 16803878
TI  - Assembly of synthetic locked chromophores with agrobacterium phytochromes Agp1
      and Agp2.
AB  - Phytochromes are photoreceptors with a bilin chromophore in which light triggers
      the conversion between the red-absorbing form Pr and the far-red-absorbing form
      Pfr. Agrobacterium tumefaciens has two phytochromes, Agp1 and Agp2, with
      antagonistic properties: in darkness, Agp1 converts slowly from Pfr to Pr,
      whereas Agp2 converts slowly from Pr to Pfr. In a previous study, we have
      assembled Agp1 with synthetic locked chromophores 15Za, 15Zs, 15Ea, and 15Es in
      which the C15=C16 double bond is fixed in either the E or Z configuration and the
      C14-C15 single bond is fixed in either the syn (s) or anti (a) conformation. In
      the present study, the locked chromophores 5Za and 5Zs were used for assembly
      with Agp1; in these chromophores, the C4=C5 double bond is fixed in the Z
      configuration, and the C5-C6 single bond is fixed in either the syn or anti
      conformation. All locked chromophores were also assembled with Agp2. The data
      showed that in both phytochromes the Pr chromophore adopts a C4=C5 Z C5-C6 syn
      C15=C16 Z C14-C15 anti stereochemistry and that in the Pfr chromophore the
      C15=C16 double bond has isomerized to the E configuration, whereas the C14-C15
      single bond remains in the anti conformation. Photoconversion shifted the
      absorption maxima of the 5Zs adducts to shorter wavelengths, whereas the 5Za
      adducts were shifted to longer wavelengths. Thus, the C5-C6 single bond of the
      Pfr chromophore is rather in an anti conformation, supporting the previous
      suggestion that during photoconversion of phytochromes, a rotation around the
      ring A-B connecting single bond occurs.

PMID- 16803880
TI  - Tracking the unfolding pathway of a multirepeat protein via tryptophan scanning:
      evidence of localized instability in the mitochondrial import receptor Tom70.
AB  - The tetratricopeptide repeat (TPR) is a degenerate 34-amino acid repeating motif
      that forms a repeating helix-turn-helix structure and is a well characterized
      mediator of protein-protein interactions. Recently, a biophysical investigation
      on one naturally occurring TPR protein, Tom70, found that the mitochondrial
      receptor displayed an unusual three-state unfolding pathway, distinct from the
      two-state model usually displayed by TPR proteins. To investigate this unusual
      behavior, we undertook a tryptophan-scanning analysis of Tom70, where both native
      and engineered tryptophan residues are used as fluorescent reporters to monitor
      the range of local and global unfolding events that comprise the unfolding
      pathway of Tom70. Specifically, seven Tom70 variants were constructed, each with
      a single tryptophan residue in each of the seven TPR repeats of Tom70. By
      combining equilibrium and kinetic fluorescent unfolding assays, with circular
      dichroism experiments, our study reveals that the unusual folding pathway of
      Tom70 is a consequence of the unfolding of two separate, autonomous TPR arrays,
      with the less stable region appearing to account for the low structural stability
      of Tom70.

PMID- 16803879
TI  - Elevated testosterone induces apoptosis in neuronal cells.
AB  - Testosterone plays a crucial role in neuronal function, but elevated
      concentrations can have deleterious effects. Here we show that supraphysiological
      levels of testosterone (micromolar range) initiate the apoptotic cascade. We used
      three criteria, annexin V labeling, caspase activity, and DNA fragmentation, to
      determine that apoptotic pathways were activated by testosterone. Micromolar, but
      not nanomolar, testosterone concentrations increased the response in all three
      assays of apoptosis. In addition, testosterone induced different concentration
      dependent Ca2+ signaling patterns: at low concentrations of testosterone (100
      nm), Ca2+ oscillations were produced, whereas high concentrations (1-10 microm)
      induced a sustained Ca2+ increase. Elevated testosterone concentrations increase
      cell death, and this effect was abolished in the presence of either inhibitors of
      caspases or the inositol 1,4,5-trisphosphate receptor (InsP3R)-mediated Ca2+
      release. Knockdown of InsP3R type 1 with specific small interfering RNA also
      abolished the testosterone-induced cell death and the prolonged Ca2+ signals. In
      contrast, knockdown of InsP3R type 3 modified neither the apoptotic response nor
      the Ca2+ signals. These results support our hypothesis that elevated testosterone
      alters InsP3R type 1-mediated intracellular Ca2+ signaling and that the prolonged
      Ca2+ signals lead to apoptotic cell death. These effects of testosterone on
      neurons will have long term effects on brain function.

PMID- 16803882
TI  - p38 Mitogen-activated protein kinase mediates free fatty acid-induced
      gluconeogenesis in hepatocytes.
AB  - Free fatty acids (FFA) are considered as a causative link between obesity and
      diabetes. In various animal models and in humans FFA can stimulate hepatic
      gluconeogenesis. Although the in vivo role of FFA in hepatic gluconeogenesis has
      been clearly established, the intracellular role of FFA and related signaling
      pathway remain unclear in the regulation of hepatic gluconeogenic gene
      transcription. In this study, we have identified p38 mitogen-activated protein
      kinase (p38) as a critical signaling component in FFA-induced transcription of
      key gluconeogenic genes. We show in primary hepatocytes that both mid- and long
      chain fatty acids (saturated or unsaturated) could activate p38 and increase
      levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, and
      peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1alpha)
      gene transcripts. The FFA-induced expression of PEPCK and PGC-1alpha genes and
      gluconeogenesis in isolated hepatocytes could be blocked by the inhibition of
      p38. Furthermore, PGC-1alpha phosphorylation by p38 was necessary for FFA-induced
      activation of the PEPCK promoter. Additionally, FFA stimulated phosphorylation of
      cAMP-response element-binding protein (CREB) through p38. The overexpression of
      the dominant-negative CREB prevented FFA-induced activation of the PEPCK
      promoter. Finally, we show that FFA activation of p38 requires protein kinase
      Cdelta. Together, our results indicate that p38 plays a critical role in FFA
      induced transcription of gluconeogenic genes, and the known gluconeogenic
      regulators, PGC-1alpha and CREB, are also integral parts of FFA-stimulated
      transcription of gluconeogenic genes.

PMID- 16803881
TI  - CprK crystal structures reveal mechanism for transcriptional control of
      halorespiration.
AB  - Halorespiration is a bacterial respiratory process in which haloorganic compounds
      act as terminal electron acceptors. This process is controlled at transcriptional
      level by CprK, a member of the ubiquitous CRP-FNR family. Here we present the
      crystal structures of oxidized CprK in presence of the ligand ortho
      chlorophenolacetic acid and of reduced CprK in absence of this ligand. These
      structures reveal that highly specific binding of chlorinated, rather than the
      corresponding non-chlorinated, phenolic compounds in the NH(2)-terminal beta
      barrels causes reorientation of these domains with respect to the central alpha
      helix at the dimer interface. Unexpectedly, the COOH-terminal DNA-binding domains
      dimerize in the non-DNA binding state. We postulate the ligand-induced
      conformational change allows formation of interdomain contacts that disrupt the
      DNA domain dimer interface and leads to repositioning of the helix-turn-helix
      motifs. These structures provide a structural framework for further studies on
      transcriptional control by CRP-FNR homologs in general and of halorespiration
      regulation by CprK in particular.

PMID- 16803883
TI  - The C terminus of the immunophilin PASTICCINO1 is required for plant development
      and for interaction with a NAC-like transcription factor.
AB  - PASTICCINO1 (PAS1) is a high molecular weight FK506-binding protein (FKBP)
      involved in the control of cell proliferation and differentiation during plant
      development. Mutations in the C-terminal region of PAS1 result in severe
      developmental defects. We show here that the C-terminal domain of PAS1 controls
      the subcellular distribution of this protein. We also demonstrated in vitro and
      in vivo, by Forster resonance energy transfer, that this C-terminal region is
      required for interaction with FAN (FKBP-associated NAC), a new member of the
      plant-specific family of NAC transcription factors. PAS1 and FAN are translocated
      into the nucleus upon auxin treatment in plant seedlings. The nuclear
      translocation of PAS1 is dependent on the presence of the C terminus of the
      protein. Finally, we showed that FAN is involved in PAS1-regulated processes
      because FAN overproduction partly complemented the pas1 phenotype. We suggest
      that PAS1 regulates the function of this NAC-like transcription factor by
      controlling its targeting to the nucleus upon plant cell division.

PMID- 16803885
TI  - Kinetic dependence to HIV-1 entry inhibition.
AB  - Infection by human immunodeficiency virus type 1 (HIV-1) involves the fusion of
      viral and cellular membranes mediated by formation of the gp41 trimer-of
      hairpins. A designed protein, 5-Helix, targets the C-terminal region of the gp41
      ectodomain, disrupting trimer-of-hairpins formation and blocking viral entry.
      Here we show that the nanomolar inhibitory potency of 5-Helix (IC50 approximately
      6 nm) is 4 orders of magnitude larger than its subpicomolar binding affinity
      (K(D) approximately 0.6 pm). This discrepancy results from the transient exposure
      of the 5-Helix binding site on gp41. As a consequence, inhibitory potency is
      determined by the association rate, not by binding affinity. For a series of 5
      Helix variants with mutations in their gp41 binding sites, the IC50 and K(D)
      values poorly correlate. By contrast, an inverse relationship between IC50 values
      and association rate constants (k(on)) extends for over 2 orders of magnitude.
      The kinetic dependence to inhibition places temporal restrictions on an
      intermediate state of HIV-1 membrane fusion and suggests that access to the C
      terminal region of the gp41 ectodomain is largely free from steric hindrance. Our
      results support the importance of association kinetics in the development of
      improved HIV-1 fusion inhibitors.

PMID- 16803884
TI  - Identification of neurite outgrowth-promoting domains of neuroglycan C, a brain
      specific chondroitin sulfate proteoglycan, and involvement of
      phosphatidylinositol 3-kinase and protein kinase C signaling pathways in
      neuritogenesis.
AB  - Neuroglycan C (NGC) is a transmembrane-type chondroitin sulfate proteoglycan that
      is exclusively expressed in the central nervous system. We report that the
      recombinant ectodomain of NGC core protein enhances neurite outgrowth from rat
      neocortical neurons in culture. Both protein kinase C (PKC) inhibitors and
      phosphatidylinositol 3-kinase (PI3K) inhibitors attenuated the NGC-mediated
      neurite outgrowth in a dose-dependent manner, suggesting that NGC promotes
      neurite outgrowth via PI3K and PKC pathways. The active sites of NGC for neurite
      outgrowth existed in the epidermal growth factor (EGF)-like domain and acidic
      amino acid (AA)-domain of the NGC ectodomain. The EGF-domain caused cells to
      extend preferentially one neurite from a soma, whereas the AA-domain caused
      several neurites to develop. The EGF-domain also enhanced neurite outgrowth from
      GABA-positive neurons, but the AA-domain did not. These results suggest that the
      EGF-domain and AA-domain have distinct functions in terms of neuritogenesis. From
      these findings, NGC can be considered to be involved in neuritogenesis in the
      developing central nervous system.

PMID- 16803886
TI  - Importance in catalysis of the 6-phosphate-binding site of 6-phosphogluconate in
      sheep liver 6-phosphogluconate dehydrogenase.
AB  - The 6-phosphate of 6-phosphogluconate (6PG) is proposed to anchor the sugar
      phosphate in the active site and aid in orientating the substrate for catalysis.
      In order to test this hypothesis, alanine mutagenesis was used to probe the
      contribution of residues in the vicinity of the 6-phosphate to binding of 6PG and
      catalysis. The crystal structure of sheep liver 6-phosphogluconate dehydrogenase
      shows that Tyr-191, Lys-260, Thr-262, Arg-287, and Arg-446 contribute a mixture
      of ionic and hydrogen bonding interactions to the 6-phosphate, and these
      interactions are likely to provide the majority of the binding energy for 6PG.
      All mutant enzymes, with the exception of T262A, exhibit an increase in K(6PG)
      that ranges from 5- to 800-fold. There is also a less pronounced increase in
      K(NADP), ranging from 3- to 15-fold, with the exception of T262A. The R287A and
      R446A mutant enzymes exhibit a dramatic decrease in V/E(t) (600- and 300-fold,
      respectively) as well as in V/K(6PG)E(t) (10(5) - and 10(4)-fold), and therefore
      no further characterization was carried out with these two mutant enzymes. No
      change in V/E(t) was observed for the Y191A mutant enzyme, whereas 20- and 3-fold
      decreases were obtained for the K260A and T262A mutant enzymes, respectively,
      resulting in a decrease in V/K(6PG)E(t) range from 3- to 120-fold. All mutant
      enzymes also exhibit at least an order of magnitude increase in 13C-isotope
      effect -1, indicating that the decarboxylation step has become more rate
      limiting. Data are consistent with significant roles for Tyr-191, Lys-260, Thr
      262, Arg-287, and Arg-446 in providing the binding energy for 6PG. In addition,
      these residues also likely ensure proper orientation of 6PG for catalysis and aid
      in inducing the conformation change that precedes, and sets up the active site
      for, catalysis.

PMID- 16803887
TI  - UV Induces p21 rapid turnover independently of ubiquitin and Skp2.
AB  - It was previously reported that low doses, but not high doses, of UV trigger the
      Skp2-mediated proteasomal degradation of the cyclin-dependent kinase inhibitor
      p21 in mammalian cells. Here we show that both UV-C and UV-B lead to decrease of
      p21 protein, but not mRNA, level in a dose-dependent fashion in all of six human
      cell lines and five mouse cell lines tested. Also, high doses of UV reduce the
      half-life of p21. High doses, but not low doses, of UV induced p21 degradation in
      both skp2-proficient and -deficient murine embryonic fibroblast cells. UV-induced
      p21 reduction was rescued by proteasome inhibitors in all human and mouse cell
      lines tested. Neither a caspase inhibitor nor small interfering RNA against skp2
      had an effect on the UV-induced p21 decrease, suggesting that this p21
      degradation pathway may not involve caspases, or Skp2. Finally, UV did not induce
      p21 ubiquitination but still induced its degradation when the E1-activating
      enzyme was inactivated in an E1 temperature-sensitive mouse embryonic fibroblast
      cell line. Altogether, these results demonstrate that UV induces p21 degradation
      through an Skp2 and ubiquitin-independent pathway.

PMID- 16803888
TI  - Rheb inhibits C-raf activity and B-raf/C-raf heterodimerization.
AB  - The Ras-Raf-MEK signaling cascade is critical for normal development and is
      activated in many forms of cancer. We have recently shown that B-Raf kinase
      interacts with and is inhibited by Rheb, the target of the GTPase-activating
      domain of the tuberous sclerosis complex 2 gene product tuberin. Here, we
      demonstrate for the first time that activation of Rheb is associated with
      decreased B-Raf and C-Raf phosphorylation at residues Ser-446 and Ser-338,
      respectively, concomitant with a decrease in the activities of both kinases and
      decreased heterodimerization of B-Raf and C-Raf. Importantly, the impact of Rheb
      on B-Raf/C-Raf heterodimerization and kinase activity are rapamycin-insensitive,
      indicating that they are independent of Rheb activation of the mammalian target
      of rapamycin-Raptor complex. In addition, we found that Rheb inhibits the
      association of B-Raf with H-Ras. Taken together, these results support a central
      role of Rheb in the regulation of the Ras/B-Raf/C-Raf/MEK signaling network.

PMID- 16803889
TI  - Structural variations in the catalytic and ubiquitin-associated domains of
      microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1
      and MARK2.
AB  - The microtubule-associated protein (MAP)/microtubule affinity regulating kinase
      (MARK)/Par-1 phosphorylates microtubule-associated proteins tau, MAP2, and MAP4
      and is involved in the regulation of microtubule-based transport. Par-1, a
      homologue of MARK in Drosophila and Caenorhabditis elegans, is essential for the
      development of embryonic polarity. Four isoforms of MARK are found in humans.
      Recently, we reported the crystal structure of the catalytic and ubiquitin
      associated domains of MARK2, an isoform enriched in brain (Panneerselvam, S.,
      Marx, A., Mandelkow, E.-M., and Mandelkow, E. (2006) Structure 14, 173-183). It
      showed that the ubiquitin-associated domain (UBA) domain has an unusual fold and
      binds to the N-terminal lobe of the catalytic domain. This is at variance with a
      previous low resolution structure derived from small angle solution scattering
      (Jaleel, M., Villa, F., Deak, M., Toth, R., Prescott, A. R., Van Aalten, D. M.,
      and Alessi, D. R. (2006) Biochem. J. 394, 545-555), which predicts binding of the
      UBA domain to the larger, C-terminal lobe. Here we report the crystal structure
      of the catalytic and UBA domain of another isoform, MARK1. Although the crystal
      packing of the two isoforms are unrelated, the overall conformations of the
      molecules are similar. Notably, the UBA domain has the same unusual conformation
      as in MARK2, and it binds at the same site. Remarkable differences occur in the
      catalytic domain at helix C, the catalytic loop, and the activation segment.

PMID- 16803890
TI  - Acid ceramidase but not acid sphingomyelinase is required for tumor necrosis
      factor-{alpha}-induced PGE2 production.
AB  - Sphingolipids are well established effectors of signal transduction downstream of
      the tumor necrosis factor (TNF) receptor. In a previous study, we showed that the
      sphingosine kinase/sphingosine 1-phosphate (S1P) pathway couples TNF receptor to
      induction of the cyclooxygenase 2 gene and prostaglandin synthesis (Pettus, B.
      J., Bielawski, J., Porcelli, A. M., Reames, D. L., Johnson, K. R., Morrow, J.,
      Chalfant, C. E., Obeid, L. M., and Hannun, Y. A. (2003) FASEB J. 17, 1411-1421).
      In this study, the requirement for acid sphingomyelinase and sphingomyelin
      metabolites in the TNFalpha/prostaglandin E(2) (PGE(2)) pathway was investigated.
      The amphiphilic compound desipramine, a frequently employed inhibitor of acid
      sphingomyelinase (ASMase), blocked PGE(2) production. However, the action of
      desipramine was independent of its action on ASMase, since neither genetic loss
      of ASMase (Niemann-Pick fibroblasts) nor knockdown of ASMase using RNA
      interference affected TNFalpha-induced PGE(2) synthesis. Further investigations
      revealed that desipramine down-regulated acid ceramidase (AC), but not
      sphingosine kinase, at the protein level. This resulted in a time-dependent drop
      in sphingosine and S1P levels. Moreover, exogenous administration of either
      sphingosine or S1P rescued PGE(2) biosynthesis after desipramine treatment.
      Interestingly, knockdown of endogenous AC by RNA interference attenuated
      cyclooxygenase 2 induction by TNFalpha and subsequent PGE(2) biosynthesis. Taken
      together, these results define a novel role for AC in the TNFalpha/PGE(2)
      pathway. In addition, the results of this study warrant careful reconsideration
      of desipramine as a specific inhibitor for ASMase.

PMID- 16803891
TI  - Evolution and function of leukocyte RNase A ribonucleases of the avian species,
      Gallus gallus.
AB  - In this study, we explore the evolution and function of two closely related RNase
      A ribonucleases from the chicken, Gallus gallus. Separated by approximately 10 kb
      on chromosome 6, the coding sequences of RNases A-1 and A-2 are diverging under
      positive selection pressure (dN > dS) but remain similar to one another (81%
      amino acid identity) and to the mammalian angiogenins. Immunoreactive RNases A-1
      and A-2 (both approximately 16 kDa) were detected in peripheral blood
      granulocytes and bone marrow. Recombinant proteins are ribonucleolytically active
      (kcat = 2.6 and 0.056 s(-1), respectively), and surprisingly, both interact with
      human placental ribonuclease inhibitor. RNase A-2, the more cationic (pI 11.0),
      is both angiogenic and bactericidal; RNase A-1 (pI 10.2) has neither activity. We
      demonstrated via point mutation of the catalytic His110 that ablation of
      ribonuclease activity has no impact on the bactericidal activity of RNase A-2. We
      determined that the divergent domains II (amino acids 71-76) and III (amino acids
      89-104) of RNase A-2 are both important for bactericidal activity. Furthermore,
      we demonstrated that these cationic domains can function as independent
      bactericidal peptides without the tertiary structure imposed by the RNase A
      backbone. These results suggest that ribonucleolytic activity may not be a
      crucial constraint limiting the ongoing evolution of this gene family and that
      the ribonuclease backbone may be merely serving as a scaffold to support the
      evolution of novel, nonribonucleolytic proteins.

PMID- 16803892
TI  - The NUG1 GTPase reveals and N-terminal RNA-binding domain that is essential for
      association with 60 S pre-ribosomal particles.
AB  - The putative yeast GTPase Nug1, which is associated with several pre-60 S
      particles in the nucleolus and nucleoplasm, consists of an N-terminal domain,
      which is found only in eukaryotic orthologues, and middle and C-terminal domains
      that are conserved throughout eukaryotes, bacteria, and archaea. Here, we
      analyzed the role of the eukaryote-specific Nug1 N-domain (Nug1-N). We show that
      the essential Nug1-N is sufficient and necessary for nucle(ol)ar targeting and
      association with pre-60 S particles. Nug1-N exhibits RNA binding activity and is
      genetically linked in an allele-specific way to the pre-60 S factors Noc2, Noc3,
      and Dbp10. In contrast, the middle domain, which exhibits a circularly permuted
      GTPase fold and an intrinsic GTP hydrolysis activity in vitro, is not essential
      for cell growth. The conserved Nug1 C-domain, which has a yet uncharacterized
      fold, is also essential for ribosome biogenesis. Our findings suggest that Nug1
      associates with pre-60 S subunits via its essential N-terminal RNA-binding domain
      and exerts a non-essential regulative role in pre-60 S subunit biogenesis via its
      central GTPase domain.

PMID- 16803893
TI  - PimE is a polyprenol-phosphate-mannose-dependent mannosyltransferase that
      transfers the fifth mannose of phosphatidylinositol mannoside in mycobacteria.
AB  - Phosphatidylinositol mannosides (PIMs) are a major class of glycolipids in all
      mycobacteria. AcPIM2, a dimannosyl PIM, is both an end product and a precursor
      for polar PIMs, such as hexamannosyl PIM (AcPIM6) and the major cell wall
      lipoglycan, lipoarabinomannan (LAM). The mannosyltransferases that convert AcPIM2
      to AcPIM6 or LAM are dependent on polyprenol-phosphate-mannose (PPM), but have
      not yet been characterized. Here, we identified a gene, termed pimE that is
      present in all mycobacteria, and is required for AcPIM6 biosynthesis. PimE was
      initially identified based on homology with eukaryotic PIG-M
      mannosyltransferases. PimE-deleted Mycobacterium smegmatis was defective in
      AcPIM6 synthesis, and accumulated the tetramannosyl PIM, AcPIM4. Loss of PimE had
      no affect on cell growth or viability, or the biosynthesis of other intracellular
      and cell wall glycans. However, changes in cell wall hydrophobicity and plasma
      membrane organization were detected, suggesting a role for AcPIM6 in the
      structural integrity of the cell wall and plasma membrane. These defects were
      corrected by ectopic expression of the pimE gene. Metabolic pulse-chase
      radiolabeling and cell-free PIM biosynthesis assays indicated that PimE catalyzes
      the alpha1,2-mannosyl transfer for the AcPIM5 synthesis. Mutation of an Asp
      residue in PimE that is conserved in and required for the activity of human PIG-M
      resulted in loss of PIM-biosynthetic activity, indicating that PimE is the
      catalytic component. Finally, PimE was localized to a distinct membrane fraction
      enriched in AcPIM4-6 biosynthesis. Taken together, PimE represents the first PPM
      dependent mannosyl-transferase shown to be involved in PIM biosynthesis, where it
      mediates the fifth mannose transfer.

PMID- 16803894
TI  - Suppression of the ligand-mediated down-regulation of epidermal growth factor
      receptor by Ymer, a novel tyrosine-phosphorylated and ubiquitinated protein.
AB  - The ligand-mediated down-regulation of the growth factor receptors is preceded by
      the involvement of various other factors. In particular, a ubiquitin ligase, Cbl,
      plays a central role in this event. Several candidates that have potential
      effects on the negative control of the epidermal growth factor (EGF) receptor
      have now been identified by our recent studies in phospho-proteomics. Among these
      molecules, we focus on characterizing a novel protein, Ymer, which is a tyrosine
      phosphorylated and ubiquitinated protein. Ymer is found to be phosphorylated at
      tyrosine 145 and 146 upon EGF stimulation, and lysine 129 of Ymer has been
      identified as a ubiquitination site. Ymer has two motifs interacting with the
      ubiquitin (MIU) domains that might function as a binding site for the
      ubiquitinated EGF receptor. Although Ymer and EGF receptors are associated in an
      EGF-dependent manner, their interaction is required not only for MIU domains but
      also for the tyrosine phosphorylation of Ymer. Phosphorylated Ymer is mainly
      located at the plasma membrane with EGF receptor and functions in its endocytosis
      and degradation. Furthermore, EGF-mediated secondary modifications of an
      activated-EGF receptor are inhibited by overexpressing Ymer in COS7 cells.
      Therefore, Ymer may have competitive effects on the activation of the EGF
      receptor. Our findings suggest that Ymer functions as a novel inhibitor for the
      down-regulation of the EGF receptor and plays a crucial role for regulating the
      amount of the EGF receptor on the cell surface membrane.

PMID- 16803895
TI  - Vasoactive intestinal peptide and PACAP38 control N-methyl-D-aspartic acid
      induced dendrite motility by modifying the activities of Rho GTPases and
      phosphatidylinositol 3-kinases.
AB  - Dendrite morphogenesis is highly dynamic and characterized by the addition and
      elongation of processes and also by their selective maintenance, retraction, and
      elimination. Glutamate can influence these events via N-methyl-d-aspartic acid
      (NMDA) receptors. The neuropeptides vasoactive intestinal peptide and pituitary
      adenylyl cyclase-activating polypeptide-38 (PACAP38) affect neurogenesis and
      differentiation in the developing nervous system. We report here that the
      peptides and NMDA acted synergistically on dendrite and branch formation. In
      stage III hippocampal neurons, NMDA increased not only the addition but also the
      elimination of new dendrites and branches by activating Rac and Cdc42 and
      phosphatidylinositol 3-kinases, respectively. When applied alone, the
      neuropeptides did not influence dendrite or branch formation. However, they
      reduced the elimination of newly formed dendrites and branches caused by NMDA by
      preventing the NMDA-induced activation of phosphatidylinositol 3-kinases. This
      led to the formation of persistent dendrites and branches. Additional timelapse
      studies on the dynamics of dendrite elongation showed alternating periods of
      elongation and retraction. Phosphatidylinositol 3-kinases increased the
      velocities of dendrite elongation and retraction, whereas the neuropeptides
      prolonged the periods of elongation. By modifying NMDA-induced activation of Rho
      GTPases and phosphatidylinositol 3-kinases, vasoactive intestinal peptide and
      PACAP38 could play an important role in the control of dendrite growth and
      branching during development and in response to neuronal activity.

PMID- 16803897
TI  - The roles of cyclin-dependent kinase 5 and glycogen synthase kinase 3 in tau
      hyperphosphorylation.
AB  - Hyperphosphorylation of the microtubule-associated protein tau is a
      characteristic feature of neurodegenerative tauopathies including Alzheimer
      disease. Over-activation of proline-directed kinases, such as cyclin-dependent
      kinase 5 (Cdk5) and glycogen synthase kinase 3 (GSK3), has been implicated in the
      aberrant phosphorylation of tau at proline-directed sites. In this study we
      tested the roles of Cdk5 and GSK3 in tau hyperphosphorylation in vivo using
      transgenic mice with p25-induced Cdk5 over-activation. We found that over
      activation of Cdk5 in young transgenic animals does not induce tau
      hyperphosphorylation at sites recognized by the antibodies AT8, AT100, PHF-1, and
      TG3. In fact, we observed that Cdk5 over-activation leads to inhibition of GSK3.
      However, in old transgenic animals the inhibition of GSK3 is lost and results in
      increased GSK3 activity, which coincides with tau hyperphosphorylation at the AT8
      and PHF-1 sites. Pharmacological inhibition of GSK3 in old transgenic mice by
      chronic treatment with lithium leads to a reduction of the age-dependent increase
      in tau hyperphosphorylation. Furthermore, we found that Cdk5, GSK3, and PP2A co
      immunoprecipitate, suggesting a functional association of these molecules.
      Together, these results reveal the role of GSK3 as a key mediator of tau
      hyperphosphorylation, whereas Cdk5 acts as a modulator of tau
      hyperphosphorylation via the inhibitory regulation of GSK3. Furthermore, these
      findings suggest that disruption of regulation of GSK3 activity underlies tau
      hyperphosphorylation in neurodegenerative tauopathies. Hence, GSK3 may be a prime
      target for therapeutic intervention in tauopathies including Alzheimer disease.

PMID- 16803898
TI  - Identification of an N-terminal transactivation domain of Runx1 that separates
      molecular function from global differentiation function.
AB  - RUNX1, or AML1, is a transcription factor that is the most frequent target for
      chromosomal gene translocations in acute leukemias. RUNX1 is essential for
      definitive hematopoiesis in embryos and profoundly influences adult steady-state
      hematopoiesis both positively and negatively. To investigate this wide range of
      normal activities and the pathological role of RUNX1, it is important to define
      the functions of different domains of the protein. RUNX1, RUNX2, and RUNX3 are
      highly conserved in their DNA binding runt homology domain and contain divergent
      sequences of unknown function N-terminal to this domain. Here we analyzed the
      role of the N-terminal sequence and the alpha-helix of the runt homology domain
      of Runx1 in DNA binding, transactivation, and megakaryocytopoiesis. Both the N
      terminus and the alpha-helix were found to reduce DNA binding of Runx1 and be
      essential for transactivation of the granulocyte-macrophage colony-stimulating
      factor and Ialpha1 promoters by Runx1. The N terminus of Runx1, including the
      alpha-helix, was also required for transactivation of a Gal4 reporter when
      expressed as fusion proteins with a Gal4 DNA binding domain, and the N terminus
      alone was capable of stimulating transcription when fused to the Gal4 DNA binding
      domain. The N terminus and the alpha-helix, however, were not required for
      megakaryocyte development from embryonic stem cells differentiated in vitro.
      Thus, our findings define a second transactivation domain of Runx1 that is
      differentially required for activation of transcription of some Runx1-dependent
      promoters and megakaryocytopoiesis.

PMID- 16803896
TI  - Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the
      platelet serotonin transporter.
AB  - Emerging data indicate the existence of multiple regulatory processes supporting
      serotonin (5HT) transporter (SERT) capacity including regulated trafficking and
      catalytic activation, influenced by post-translational modifications and
      transporter-associated proteins. In the present study, using differential
      extraction and sedimentation procedures optimized for the purification of
      cytoskeletal and membrane-skeletal associated proteins, we analyze SERT
      localization in platelets. We find that most of the plasma membrane SERT is
      associated with the membrane skeleton. This association can be enhanced by both
      transporter activation and 5HT2A receptor activation. Inactivation of transport
      activity by phorbol ester treatment of intact platelets relocates SERT to the
      cytoskeleton fraction, consequently leading to transporter internalization. The
      translocation of SERT between these compartments is correlated with changes in
      the interaction with the LIM domain adaptor protein Hic-5. Co-immunoprecipitation
      and uptake activity studies suggest that Hic-5 is a determinant of transporter
      inactivation and relocation to a compartment subserving endocytic regulation.
      Associations of SERT with Hic-5 are evident in brain synaptosomes, suggesting the
      existence of parallel mechanisms operating to regulate SERT at serotonergic
      synapses.

PMID- 16803899
TI  - Probing active site chemistry in SHV beta-lactamase variants at Ambler position
      244. Understanding unique properties of inhibitor resistance.
AB  - Inhibitor-resistant class A beta-lactamases are an emerging threat to the use of
      beta-lactam/beta-lactamase inhibitor combinations (e.g. amoxicillin/clavulanate)
      in the treatment of serious bacterial infections. In the TEM family of Class A
      beta-lactamases, single amino acid substitutions at Arg-244 confer resistance to
      clavulanate inactivation. To understand the amino acid sequence requirements in
      class A beta-lactamases that confer resistance to clavulanate, we performed site
      saturation mutagenesis of Arg-244 in SHV-1, a related class A beta-lactamase
      found in Klebsiella pneumoniae. Twelve SHV enzymes with amino acid substitutions
      at Arg-244 resulted in significant increases in minimal inhibitory concentrations
      to ampicillin/clavulanate when expressed in Escherichia coli. Kinetic analyses of
      SHV-1, R244S, R244Q, R244L, and R244E beta-lactamases revealed that the main
      determinant of clavulanate resistance was reduced inhibitor affinity. In contrast
      to studies in the highly similar TEM enzyme, we observed increases in clavulanate
      k(inact) for all mutants. Electrospray ionization mass spectrometry of
      clavulanate inhibited SHV-1 and R244S showed nearly identical mass adducts,
      arguing against a difference in the inactivation mechanism. Testing a wide range
      of substrates with C3-4 carboxylates in different stereochemical orientations, we
      observed impaired affinity for all substrates among inhibitor resistant variants.
      Lastly, we synthesized two boronic acid transition state analogs that mimic
      cephalothin and found substitutions at Arg-244 markedly affect both the affinity
      and kinetics of binding to the chiral, deacylation transition state inhibitor.
      These data define a role for Arg-244 in substrate and inhibitor binding in the
      SHV beta-lactamase.

PMID- 16803901
TI  - Role of single-stranded DNA in targeting REV1 to primer termini.
AB  - Cellular functions of the REV1 gene have been conserved in evolution and appear
      important for maintaining genetic integrity through translesion DNA synthesis.
      This study documents a novel biochemical activity of human REV1 protein, due to
      higher affinity for single-stranded DNA (ssDNA) than the primer terminus.
      Preferential binding to long ssDNA regions of the template strand means that REV1
      is targeted specifically to the included primer termini, a property not shared by
      other DNA polymerases, including human DNA polymerases alpha, beta, and eta.
      Furthermore, a mutant REV1 lacking N- and C-terminal domains, but catalytically
      active, lost this function, indicating that control is not due to the catalytic
      core. The novel activity of REV1 protein might imply a role for ssDNA in the
      regulation of translesion DNA synthesis.

PMID- 16803900
TI  - Alpha-conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as
      well as alpha3beta2 and alpha7 nicotinic acetylcholine receptors.
AB  - The molluskan acetylcholine-binding protein (AChBP) is a homolog of the
      extracellular binding domain of the pentameric ligand-gated ion channel family.
      AChBP most closely resembles the alpha-subunit of nicotinic acetylcholine
      receptors and in particular the homomeric alpha7 nicotinic receptor. We report
      the isolation and characterization of an alpha-conotoxin that has the highest
      known affinity for the Lymnaea AChBP and also potently blocks the alpha7 nAChR
      subtype when expressed in Xenopus oocytes. Remarkably, the peptide also has high
      affinity for the alpha3beta2 nAChR indicating that alpha-conotoxin OmIA in
      combination with the AChBP may serve as a model system for understanding the
      binding determinants of alpha3beta2 nAChRs. alpha-Conotoxin OmIA was purified
      from the venom of Conus omaria. It is a 17-amino-acid, two-disulfide bridge
      peptide. The ligand is the first alpha-conotoxin with higher affinity for the
      closely related receptor subtypes, alpha3beta2 versus alpha6beta2, and
      selectively blocks these two subtypes when compared with alpha2beta2,
      alpha4beta2, and alpha1beta1deltaepsilon nAChRs.

PMID- 16803903
TI  - The histone variant macro-H2A preferentially forms "hybrid nucleosomes".
AB  - The histone domain of macro-H2A, which constitutes the N-terminal one third of
      this histone variant, is only 64% identical to major H2A. We have shown
      previously that the main structural differences in a nucleosome in which both H2A
      moieties have been replaced by macro-H2A reside in the only point of contact
      between the two histone dimers, the L1-L1 interface of macro-H2A. Here we show
      that the L1 loop of macro-H2A is responsible for the increased salt-dependent
      stability of the histone octamer, with implications for the nucleosome assembly
      pathway. It is unknown whether only one or both of the H2A-H2B dimers within a
      nucleosome are replaced with H2A variant containing nucleosomes in vivo. We
      demonstrate that macro-H2A preferentially forms hybrid nucleosomes containing one
      chain each of major H2A and macro-HA in vitro. The 2.9-A crystal structure of
      such a hybrid nucleosome shows significant structural differences in the L1-L1
      interface when comparing with homotypic major H2A- and macro-H2A-containing
      nucleosomes. Both homotypic and hybrid macro-nucleosome core particles (NCPs) are
      resistant to chaperone-assisted H2A-H2B dimer exchange. Together, our findings
      suggest that the histone domain of macro-H2A modifies the dynamic properties of
      the nucleosome. We propose that the possibility of forming hybrid macro-NCP adds
      yet another level of complexity to variant nucleosome structure and function.

PMID- 16803904
TI  - The chicken ovalbumin upstream promoter-transcription factors modulate genes and
      pathways involved in skeletal muscle cell metabolism.
AB  - The chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) are
      "orphan" members of the nuclear hormone receptor (NR) superfamily. COUP-TFs are
      involved in organogenesis and neurogenesis. However, their role in skeletal
      muscle (and other major mass tissues) and metabolism remains obscure. Skeletal
      muscle accounts for approximately 40% of total body mass and energy expenditure.
      Moreover, this peripheral tissue is a primary site of glucose and fatty acid
      utilization. We utilize small interfering RNA (siRNA)-mediated attenuation of
      Coup-TfI and II (mRNA and protein) in a skeletal muscle cell culture model to
      understand the regulatory role of Coup-Tfs in this energy demanding tissue. This
      targeted NR repression resulted in the significant attenuation of genes that
      regulate lipid mobilization and utilization (including Pparalpha, Fabp3, and Cpt
      1). This was coupled to reduced fatty acid beta-oxidation. Additionally we
      observed significant attenuation of Ucp1, a gene involved in energy expenditure.
      Concordantly, we observed a 5-fold increase in ATP levels in cells with siRNA
      mediated repression of Coup-TfI and II. Furthermore, the expression of
      "classical" liver X receptor (LXR) target genes involved in reverse cholesterol
      transport (Abca1 and Abcg1) were both significantly repressed. Moreover, we
      observed that repression of the Coup-Tfs ablated the activation of Abca1, and
      Abcg1 mRNA expression by the selective LXR agonist, T0901317. In concordance,
      Coup-Tf-siRNA-transfected cells were refractory to Lxr-mediated reduction of
      total intracellular cholesterol levels in contrast to the negative control cells.
      In agreement Lxr-mediated activation of the Abca1 promoter in Coup-Tf-siRNA cells
      was attenuated. Collectively, these data suggest a pivotal role for Coup-Tfs in
      the regulation of lipid utilization/cholesterol homeostasis in skeletal muscle
      cells and the modulation of Lxr-dependent gene regulation.

PMID- 16803902
TI  - Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post
      ubiquitination mechanism.
AB  - Inhibition of the MDM2-p53 feedback loop is critical for p53 activation in
      response to cellular stresses. The ribosomal proteins L5, L11, and L23 can block
      this loop by inhibiting MDM2-mediated p53 ubiquitination and degradation in
      response to ribosomal stress. Here, we show that L11, but not L5 and L23, leads
      to a drastic accumulation of ubiquitinated and native MDM2. This effect is
      dependent on the ubiquitin ligase activity of MDM2, but not p53, and requires the
      central MDM2 binding domain (residues 51-108) of L11. We further show that L11
      inhibited 26 S proteasome-mediated degradation of ubiquitinated MDM2 in vitro and
      consistently prolonged the half-life of MDM2 in cells. These results suggest that
      L11, unlike L5 and L23, differentially regulates the levels of ubiquitinated p53
      and MDM2 and inhibits the turnover and activity of MDM2 through a post
      ubiquitination mechanism.

PMID- 16803906
TI  - Association of calpastatin with inactive calpain: a novel mechanism to control
      the activation of the protease?
AB  - It is generally accepted that the Ca(2+)-dependent interaction of calpain with
      calpastatin is the most relevant mechanism involved in the regulation of Ca(2+)
      induced proteolysis. We now report that a calpain-calpastatin association can
      occur also in the absence of Ca(2+) or at very low Ca(2+) concentrations,
      reflecting the physiological conditions under which calpain retains its inactive
      conformational state. The calpastatin binding region is localized in the non
      inhibitory L-domain containing the amino acid sequences encoded by exons 4-7.
      This calpastatin region recognizes a calpain sequence located near the end of the
      DII-domain. Interaction of calpain with calpastatins lacking these sequences
      becomes strictly Ca(2+)-dependent because, under these conditions, the transition
      to an active state of the protease is an obligatory requirement. The occurrence
      of the molecular association between Ca(2+)-free calpain and various recombinant
      calpastatin forms has been demonstrated by the following experimental results.
      Addition of calpastatin protected calpain from trypsin digestion. Calpain was
      coprecipitated when calpastatin was immunoprecipitated. The calpastatin molecular
      size increased following exposure to calpain. The two proteins comigrated in
      zymogram analysis. Furthermore, calpain-calpastatin interaction was perturbed by
      protein kinase C phosphorylation occurring at sites located at the exons involved
      in the association. At a functional level, calpain-calpastatin interaction at a
      physiological concentration of Ca(2+) represents a novel mechanism for the
      control of the amount of the active form of the protease potentially generated in
      response to an intracellular Ca(2+) influx.

PMID- 16803905
TI  - Heterodimerization of CCR2 chemokines and regulation by glycosaminoglycan
      binding.
AB  - Despite the wide range of sequence diversity among chemokines, their tertiary
      structures are remarkably similar. Furthermore, many chemokines form dimers or
      higher order oligomers, but all characterized oligomeric structures are based
      primarily on two dimerization motifs represented by CC-chemokine or CXC-chemokine
      dimer interfaces. These observations raise the possibility that some chemokines
      could form unique hetero-oligomers using the same oligomerization motifs. Such
      interactions could modulate the overall signaling response of the receptors,
      thereby providing a general mechanism for regulating chemokine function. For some
      chemokines, homo-oligomerization has also been shown to be coupled to
      glycosaminoglycan (GAG)-binding. However, the effect of GAG binding on chemokine
      hetero-oligomerization has not yet been demonstrated. In this report, we
      characterized the heterodimerization of the CCR2 ligands MCP-1 (CCL2), MCP-2
      (CCL8), MCP-3 (CCL7), MCP-4 (CCL13), and eotaxin (CCL11), as well as the effects
      of GAG binding, using electrospray ionization Fourier transform ion cyclotron
      resonance (ESI-FTICR) mass spectrometry. Strong heterodimerization was observed
      between CCL2 and CCL8 at the expense of homodimer formation. Using NMR, we showed
      that the heterodimer is predominant in solution and forms a specific CC chemokine
      like dimer. By contrast, only moderate heterodimer formation was observed between
      CCL2.CCL13, CCL2.CCL11 and CCL8.CCL13, and no heterodimerization was observed
      when any other CCR2 ligand was added to CCL7. To investigate the effect of a
      highly sulfated GAG on the formation of heterodimers, each chemokine pair was
      mixed with the heparin pentasaccharide, Arixtra, and assayed by ESI-FTICR mass
      spectrometry. Although no CCL8.CCL11 heterodimer was observed in the absence of
      GAG, abundant ions corresponding to the ternary complex, CCL8.CCL11.Arixtra, were
      observed upon addition of Arixtra. Heterodimerization between CCL2 and CCL11 was
      also enhanced in the presence of Arixtra. In summary, these results indicate that
      some CCR2 ligands can form stable heterodimers in preference to homodimers and
      that these interactions, like those of homo-oligomers, can be influenced by some
      GAGs.

PMID- 16803908
TI  - Senescence: the last half of life. 1922.

PMID- 16803909
TI  - The oral examination process - gold standard or fool's gold.

PMID- 16803910
TI  - Is anesthesia good for you? Timing is everything!

PMID- 16803907
TI  - Crystal structure and binding properties of the CD2 and CD244 (2B4)-binding
      protein, CD48.
AB  - The structural analysis of surface proteins belonging to the CD2 subset of the
      immunoglobulin superfamily has yielded important insights into transient cellular
      interactions. In mice and rats, CD2 and CD244 (2B4), which are expressed
      predominantly on T cells and natural killer cells, respectively, bind the same,
      broadly expressed ligand, CD48. Structures of CD2 and CD244 have been solved
      previously, and we now present the structure of the receptor-binding domain of
      rat CD48. The receptor-binding surface of CD48 is unusually flat, as in the case
      of rat CD2, and shares a high degree of electrostatic complementarity with the
      equivalent surface of CD2. The relatively simple arrangement of charged residues
      and this flat topology explain why CD48 cross-reacts with CD2 and CD244 and, in
      rats, with the CD244-related protein, 2B4R. Comparisons of modeled complexes of
      CD2 and CD48 with the complex of human CD2 and CD58 are suggestive of there being
      substantial plasticity in the topology of ligand binding by CD2. Thermodynamic
      analysis of the native CD48-CD2 interaction indicates that binding is driven by
      equivalent, weak enthalpic and entropic effects, in contrast to the human CD2
      CD58 interaction, for which there is a large entropic barrier. Overall, the
      structural and biophysical comparisons of the CD2 homologues suggest that the
      evolutionary diversification of interacting cell surface proteins is rapid and
      constrained only by the requirement that binding remains weak and specific.

PMID- 16803911
TI  - Intraoperative infusion of dexmedetomidine reduces perioperative analgesic
      requirements.
AB  - PURPOSE: This prospective, randomized, double-blind study was designed to assess
      whether intraoperative infusion of dexmedetomidine provides effective
      postoperative analgesia. Postoperative pain scores and morphine consumption were
      compared in a treated group and a placebo group, both of which received patient
      controlled morphine after total abdominal hysterectomy. METHODS: Fifty women were
      randomly assigned to two groups. Group D (n = 25) received a loading dose of
      dexmedetomidine 1 mug.kg(-1) iv during induction of anesthesia, followed by a
      continuous infusion at a rate of 0.5 mug.kg(-1).hr(-1) throughout the operation.
      Group P (n = 25) received a volume-matched bolus and infusion of placebo (0.9%
      saline). For each case, heart rate, peripheral oxygen saturation, and systolic
      and diastolic blood pressure were recorded intraoperatively and for 48 hr
      postoperatively. Patients used a patient-controlled analgesia device to receive
      bolus doses of morphine after surgery. Total morphine consumption, pain scores,
      and sedation scores were recorded for the first 48 hr (two hours in the
      postanesthesia care unit and 46 hr on the ward). RESULTS: The groups were similar
      with respect to mean times to extubation of the trachea. Pain and sedation scores
      were also similar between groups at all corresponding times throughout the 48-hr
      period of observation. Group D patients consumed significantly less morphine in
      the postanesthesia care unit and on the ward (P < 0.05 and P < 0.01,
      respectively). Fewer patients in Group D experienced itching or nausea/vomiting
      (P < 0.05). CONCLUSION: Continuous iv dexmedetomidine during abdominal surgery
      provides effective postoperative analgesia, and reduces postoperative morphine
      requirements without increasing the incidence of side effects.

PMID- 16803912
TI  - Behavioural effects of chronic exposure to subanesthetic concentrations of
      halothane, sevoflurane and desflurane in rats.
AB  - BACKGROUND: A double-blind, randomized trial was conducted to determine the
      behavioural effects of chronic exposure to subanesthetic concentrations of
      halothane, sevoflurane and desflurane in rats. METHODS: Halothane, sevoflurane
      and desflurane group rats received 0.1%, 0.3%, and 0.6% concentrations in a flow
      rate of 3 L.min(-1) O(2) respectively. Control animals also received 3 L.min(-1)
      O(2) in another investigation room, which had the same properties as the study
      group rooms. Rats breathed inhaled agents or oxygen between 09:00-13:00 hr every
      day for 30 days. After 30 days of inhalation of subanesthetic doses of inhaled
      agents or oxygen, behavioural tests were applied. RESULTS: Tests of exploratory
      activity and curiosity (hole-board test), anxiety (elevated plus maze test) and
      learning and memory functions (multiple T maze test), demonstrated that chronic
      exposure to subanesthetic concentrations of all three anesthetics alters
      behavioural functions in rats. However, impairment of learning (P<0.05) and
      memory function (P<0.05) were greater in association with desflurane, in
      comparison to halothane and sevoflurane-treated rats. CONCLUSION: Chronic
      exposure to subanesthetic concentrations of halothane, sevoflurane and desflurane
      is associated with behavioural change in rats. Of the three drugs, desflurane was
      associated with the lowest learning and memory function test scores.

PMID- 16803913
TI  - Poor inter-rater reliability on mock anesthesia oral examinations.
AB  - PURPOSE: Inter-rater reliability (IRR) and communication skills are both
      important factors that have been shown to affect oral examination scores. This
      study was designed to test: 1) IRR of a group of American Board of Anesthesiology
      (ABA) and the Royal College of Physicians and Surgeons of Canada (RCPSC) graders
      who graded in true isolation; 2) the effect of teaching residents examination
      techniques. METHODS: This was a randomized, pretest-posttest trial. Twenty-five
      residents did an initial oral examination (E1) resembling the ABA examination.
      They were then randomized into two groups, a routine education group, and an
      intervention group that was taught oral examination skills. Six weeks later they
      did another oral examination (E2). The videotaped examinations were subsequently
      scored by six experienced RCPSC and ABA graders. RESULTS: There was very poor IRR
      on E1 (weighted Kappa = 0.166, intraclass correlation coefficient 0.243), which
      improved only slightly on E2 (weighted Kappa = 0.275, P = NS; intraclass
      correlation coefficient = 0.405, P < 0.01). Pass rate for graderpairs increased
      from E1 to E2 (15% vs 43%, P = 0.01). The improved pass rate on E2 occurred in
      both the routine education group and in the intervention group. There was no
      significant difference between RCPSC and ABA graders. Teaching examination skills
      per se did not improve performance, but this conclusion may be limited by the
      poor IRR. Practice orals do appear to improve performance on future examinations.
      CONCLUSIONS: Inter-rater reliability may be poor when graders score an oral
      examination in true isolation. Teaching candidates an oral examination
      communication and presentation technique did not appear to improve performance.
      Oral examination practice may be of value in training for future examinations.

PMID- 16803914
TI  - Evidence-based clinical update: general anesthesia and the risk of delirium and
      postoperative cognitive dysfunction.
AB  - PURPOSE: The purpose of this structured, evidence-based, clinical update was to
      identify the best evidence comparing general and regional anesthesia and their
      influence on delirium or cognitive dysfunction (POCD) in the postoperative
      period. SOURCE: In June 2005 a structured search of MEDLINE from 1966 to present
      using OVID software was undertaken. Medical subject headings and textwords
      describing both delirium and POCD were employed. OVID's Therapy (sensitivity)
      algorithm was used to maximize the detection of randomized trials. The
      bibliographies of eligible publications were hand-searched to identify trials not
      identified in the electronic search. Publications enrolling children were
      excluded. Levels of evidence and grades of recommendations were scored using
      Centre for Evidence Based Medicine criteria. PRINCIPAL FINDINGS: A total of 18
      unique randomized controlled trials were identified: two evaluating delirium; ten
      evaluating POCD; and six evaluating both. Outcomes for delirium were abstracted
      from eight trials that enrolled 765 patients (387 regional anesthesia; 378
      general anesthesia). Outcomes for POCD were identified from 16 trials that
      enrolled 2,708 patients (1,313 regional anesthesia; 1,395 general anesthesia).
      Both delirium (11-43%) and POCD (15-25%) were relatively common in trials
      actively seeking these outcomes. Consistent Level 2b evidence suggests no
      significant increase in delirium in patients receiving general anesthesia
      compared with those receiving regional anesthesia. Similarly, consistent Level 1
      evidence indicates that exposure to general anesthesia is not significantly
      associated with POCD. CONCLUSION: Available randomized controlled trials suggest
      that there is no significant difference in the incidence of delirium or POCD when
      general anesthesia and regional anesthesia are compared.

PMID- 16803915
TI  - Case report: profound hypotension associated with labetalol therapy in a patient
      with cerebral aneurysms and subarachnoid hemorrhage.
AB  - PURPOSE: Labetalol is an effective antihypertensive medication frequently used to
      treat systemic hypertension in acute care settings, including the management of
      hypertension associated with a subarachnoid hemorrhage. We present a case of
      profound hypotension, refractory to inotropic and vasopressor therapy following
      an iv infusion of labetalol. CLINICAL FEATURES: Initiation of an iv labetalol
      infusion resulted in good blood pressure control in a patient suffering from a
      Fisher grade 3 subarachnoid hemorrhage with an initial Glascow coma scale of
      14/15 and mild hydrocephalus. Progressive deterioration of neurological symptoms
      and evidence of worsening hydrocephalus preceded the sudden development of
      profound hypotension (60/35 mmHg) and bradycardia with a minimum heart rate of 40
      beats.min(-1). Initial resuscitative efforts included administration of
      intravascular fluid, hypertonic saline, atropine, adrenalin (more than 10 mg in
      divided doses) and noradrenalin. These measures restored the blood pressure to
      80/45 with a HR of 98 beats.min(-1). Intraoperative placement of an
      intraventricular drain released cerebrospinal fluid under pressure with an
      initial intracranial pressure of 15 cm H(2)O. A combination of adrenalin,
      noradrenalin, dopamine and vasopressin infusions were required to restore the
      blood pressure to 130/65 mmHg after an additional two hours. All inotropic and
      vasopressor support was weaned off after the 14th hr (about two drug half-lives).
      The patient was awake and responsive the following day, with no obvious
      neurological consequences. No evidence of neurological injury, drug
      administration error or myocardial dysfunction was documented. CONCLUSION: The
      episode of profound hypotension which occurred after initiating a labetolol
      infusion required maximal combined vasopressor therapy to restore the blood
      pressure suggesting that this patient demonstrated an extreme sensitivity to
      labetalol. Combination therapy with adrenergic and nonadrenergic agonists may be
      required for optimal treatment of profound hypotension associated with labetalol
      induced vasoplegia.

PMID- 16803916
TI  - Case series: monocular visual loss associated with subarachnoid hemorrhage
      secondary to ruptured intracranial aneurysms.
AB  - PURPOSE: To describe variations in the presentation of monocular visual loss
      associated with intracranial aneurysm rupture. The clinical course, possible
      etiologies and management of visual loss in three patients are described.
      CLINICAL FEATURES: The first patient developed Terson's syndrome (vitreal
      hemorrhage associated with raised intracranial pressure secondary to subarachnoid
      hemorrhage). Following aneursymal clipping, her postoperative management was
      conservative and there was no improvement in visual acuity. The second patient
      underwent surgical clipping of internal carotid aneursysms and sustained visual
      loss subsequent to surgical dissection and temporary clipping around the optic
      nerve and anterior choroidal artery. The vessel subsequently thrombosed.
      Potential contributing factors to visual loss in this case included
      intraoperative hypotension and anemia. This patient received anti-platelet
      medications, and experienced subsequent improvement in visual acuity to 6/9. A
      third patient underwent a right orbito-frontal keyhole craniotomy with the
      cranial flap retracted across the orbit. Elevated intraocular pressure secondary
      to external orbital compression may have compromised retinal and choroidal
      perfusion. This patient also developed vasospasm of both anterior cerebral
      arteries which resolved partially with papaverine therapy. Hypertension
      hypervolemia therapy was instituted, with subsequent partial recovery of visual
      acuity in her right eye. CONCLUSION: Perioperative monocular visual loss
      associated with intracranial aneurysm repair is an infrequent occurrence, and
      clinical presentations may be quite variable. The primary pathophysiological
      mechanisms are intraocular hemorrhage and ischemia of ocular structures,
      including the optic nerve. Early detection, via regular fundoscopic examination
      and treatment aimed at decreasing intraocular pressure and augmenting ocular
      perfusion may improve outcomes.

PMID- 16803917
TI  - Pain relief and functional status after vaginal hysterectomy: intrathecal versus
      general anesthesia.
AB  - PURPOSE: We tested the hypothesis that the use of subarachnoid block (SAB) for
      vaginal hysterectomy produces superior postoperative analgesia and improves
      functional status at 12 weeks postoperatively. METHODS: In this randomized
      controlled trial 89 patients received either standardized general anesthesia vs
      SAB with bupivacaine, clonidine, and morphine. Postoperatively, patients in both
      groups received multimodal pain management. Primary outcomes included evaluation
      of pain and functional status (SF-36 Health Survey) over the 12 postoperative
      weeks. RESULTS: Pain was well controlled throughout the study, as judged from the
      average pain numerical scale scores of < or = 3 in both groups, at all times
      studied. Intrathecal analgesia lessened pain and decreased the use of morphine
      both in the postanesthesia care unit (PACU) and over the first 12 hr after
      discharge from the PACU (P < 0.001). Although patients who received SAB had a
      lower frequency of postoperative nausea in the PACU than the patients in the
      general anesthesia group (P = 0.021), this effect was not extended beyond the
      PACU stay. Subarachnoid block did not affect the length of hospitalization. At
      the two-week follow-up 69% of patients in the SAB group and 48% patients in the
      general anesthesia group were pain free (P = 0.044). At all evaluation intervals
      patients' functional status was comparable between the SAB and general anesthesia
      group. CONCLUSIONS: A significantly better immediate postoperative analgesia was
      present in the SAB group, and the duration was consistent with the expected
      action of intrathecally administered drugs. Two weeks after surgery a higher
      percentage of the patients in the SAB group reported no pain. However, SAB had no
      effect on either length of hospitalization or patients' postoperative functional
      status.

PMID- 16803919
TI  - Case report: optimizing intraoperative detection of pulmonary embolism using
      contrast-enhanced echocardiography.
AB  - PURPOSE: Perioperative pulmonary embolism (PE) is associated with significant
      morbidity and mortality. Intraoperatively, the clinical management of patients
      with PE can be enhanced by the use of transesophageal echocardiography (TEE) to
      visualize emboli, assess pulmonary artery (PA) anatomy, and monitor the function
      of the right ventricle. However, the sensitivity of intraoperative TEE to detect
      thromboemboli is reported to be below 50%. In this report, we describe the use of
      contrast-enhanced TEE (CE-TEE) to improve the visualization of PE. CLINICAL
      FEATURES: A 44-yr-old female with chronic thrombo-embolic pulmonary hypertension
      was scheduled for pulmonary thromboendarterectomy. The precardiopulmonary bypass
      TEE exam demonstrated signs of PA obstruction and right ventricle dysfunction,
      but the borders of the thrombus in the right PA were only minimally visualized.
      Perflutren lipid microspheres, composed of octafluoropropane encapsulated in an
      outer lipid shell, were injected as a 0.3 mL iv bolus, while visualizing the
      right PA with harmonic ultrasound imaging. The CE-TEE image clearly visualized a
      large mobile thrombus along with a distinct pattern consistent with pulmonary
      flow obstruction. The postcardiopulmonary bypass CE-TEE confirmed thrombus
      evacuation and absence of PA flow abnormalities. CONCLUSION: Contrast-enhanced
      TEE may decrease operator dependency and increase the sensitivity necessary to
      detect central, surgically accessible PE.

PMID- 16803918
TI  - Laboratory investigation: effects of propofol on the systemic inflammatory
      response during aortic surgery.
AB  - PURPOSE: A laboratory investigation was undertaken to assess the effects of
      propofol on renal function, through modulation of the systemic inflammatory
      response, in an in vivo experimental model of aortic surgery in comparison with
      sevoflurane. METHODS: Twenty young male piglets were anesthetized with either
      propofol 4 mg.kg(-1).hr(-1) (n = 10) or sevoflurane 1.5% end-tidal concentration
      (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic
      clamping for 30 min. At specific intervals (basal -before the start of surgery;
      reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery,
      and on the seventh day after surgery) the levels of the following were
      determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor
      alpha, interleukin 1-ss, and interferon-gamma; kidney superoxide anion and its
      detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the
      activity of inducible nitric oxide synthase. Seven days after surgery, the
      animals were anesthetized using the described techniques, and after blood
      withdrawal and kidney sampling they were sacrificed. RESULTS: In comparison with
      sevoflurane, propofol was associated with a lower concentration of plasma
      creatinine (P < 0.05) together with lower concentrations of myeloperoxidase,
      tumour necrosis factor-alpha, interleukin 1-ss, interferon-gamma, superoxide
      anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide
      synthase (P < 0.05). CONCLUSION: In an experimental model of aortic
      reconstructive surgery, and compared with sevoflurane, propofol anesthesia is
      associated with less neutrophil infiltration, lower plasma proinflammatory
      cytokine levels, lower production of oxygen free radicals, less lipid
      peroxidation, and reduced inducible nitric oxide synthase activity. These
      observations suggest a possible renal protective effect of propofol in this
      surgical setting.

PMID- 16803920
TI  - Brain death diagnoses and evaluation of the number of potential organ donors in
      Quebec hospitals.
AB  - PURPOSE: Faced with our inability to respond to the growing number of Quebec
      patients waiting for organ transplants, we sought to determine the number of
      potential organ donors (OD) in acute care hospitals. METHODS: A retrospective
      chart review of all acute care, in-hospital deaths in Quebec in the year 2000 was
      undertaken. Hospital record librarians provided statistics and completed
      questionnaires on each chart after applying exclusion and inclusion criteria.
      RESULTS: There were 24,702 acute care in-hospital deaths reported by 83 hospitals
      participating in the study on a voluntary basis. Analyzing 2,067 files meeting
      inclusion criteria, we identified 348 potential OD (1.4% of deaths). In hospitals
      not providing tertiary adult trauma care, the potential donor rate was 0.99% of
      all deaths. There were 4.5 times more potential donors in tertiary care adult
      trauma centers. Brain death was formally diagnosed in 268/348 patients, and organ
      donation discussed as an option with 230/268 families. Consent for donation was
      given in 70% of cases, although not all these patients proved to be suitable
      after evaluation. There were 125 actual donors in Quebec in the year 2000 (18 per
      million population). CONCLUSIONS: The gap between used and potential donors can
      be explained by several factors including failure to approach families for organ
      donation, family refusal, incomplete neurological assessment of patients, and
      medical unsuitability of some consented donors. There is room for improvement in
      the identification of potential donors and in the presentation of organ donation
      as an end of life option to families.

PMID- 16803921
TI  - Number of deaths by neurological criteria, and organ and tissue donation rates at
      three critical care centres in Canada.
AB  - PURPOSE: Comparative organ donation rates are expressed per million population
      and by this measurement, Canada lags behind other countries. These estimates do
      not account for differing demographics and health patterns of populations which
      can result in different rates of death by neurological criteria and subsequent
      donation rates. We sought to measure directly the number of deaths by
      neurological criteria, the associated donation rates, and the reasons for the
      differences. METHODS: A prospective evaluation of deaths by neurological and
      cardiorespiratory criteria in the critical care areas of three major adult
      Canadian tertiary care centres over a seven month period was undertaken. Patients
      were assessed for eligibility for organ and tissue donation and ultimate
      disposition. RESULTS: Annualized rates of death by neurological criteria varied
      from 2.3%-7.5% (8.6-28 patients) of all deaths. Conversion to actual donors
      ranged from 20-86%, with family refusal rates accounting for most of this
      variation. There were only three cases of suspected death by neurological
      criteria where a complete examination was not performed. CONCLUSIONS: There is
      substantial geographic variability in the rate of neurological death and actual
      organ donation rates in these Canadian tertiary care centres. These variations
      are principally related to regional differences in demographics of brain injury,
      referral patterns and donation consent rates, rather than lack of identification
      of potential donors.

PMID- 16803922
TI  - Benchmarking performance in organ donation programs: dependence on demographics
      and mortality rates.
AB  - PURPOSE: Donors whose diagnosis of death is based upon neurologic criteria are
      the primary source of organs for human transplantation. The current measure of
      effectiveness of organ donation programs is the crude statistic, donors per
      million population (DPMP). This statistic represents the number of available
      donors, divided by the potential donor population. Comparisons between
      transplantation programs are done using the DPMP statistic. We sought to
      determine if variance in organ donation rates, reported as DPMP could be
      accounted for by differences in population demographics, specifically age and
      gender-specific mortality rates. METHODS: We obtained the population distribution
      and deaths for the year 2000 for the Calgary Health Region (CHR) and the country
      of Spain. Expected deaths were then calculated by standardizing the sample, based
      upon weighted averages of age, gender and cause-specific mortality rates.
      RESULTS: In 2000, Spain reported a crude organ donation rate of 33.9 DPMP.
      Standardizing the observed deaths in Spain using the CHR population distribution
      and calculating expected deaths based on the CHR rates, resulted in an adjusted
      rate of 19.2 DPMP (P < 0.05). CONCLUSIONS: These results bring into question the
      reliability of using crude DPMP as a measure of organ and tissue donation program
      performance. Alternative measures of benchmarking performance in organ donation
      programs should be considered.

PMID- 16803923
TI  - Potential organ donors referred to Ontario neurosurgical centres.
AB  - PURPOSE: Eleven hospitals in Ontario are adult neurosurgical centres (ONCs).
      Patients transferred to ONCs from community hospitals with acute intracranial
      emergencies often have non-survivable injuries, and may be returned to the
      referring hospital for end-of-life care. These referring hospitals may not be
      familiar with neurological determination of death, or organ donation. Our
      objective was to determine the number of patients with severe brain injuries
      assessed in ONC emergency departments where progression to brain death may be
      reasonably expected, and to determine their outcome. METHODS: A one-year
      retrospective cohort study was undertaken using a convenience sample of patients
      transferred to eight ONCs for neurosurgical assessment, with evidence of either
      (a) brain death in the emergency department, or (b) severe brain injury who met
      criteria of a reasonable likelihood of progression to brain death. The outcome of
      these patients to disposition from the ONC was determined by chart review.
      RESULTS: Three thousand four hundred and forty-seven patients were identified of
      whom 141 met inclusion criteria. Eleven patients (7.8%) were pronounced dead in
      the emergency department, 96 (68.1%) patients were admitted, and 34 (24.1%) were
      transferred back to their referring hospital. Fourteen patients (9.9%) became
      organ donors: two died in the emergency department and 12 died following
      admission. CONCLUSIONS: A significant number of patients transferred to ONCs have
      an injury with a likelihood of progressing to brain death, but only a small
      proportion of these patients become organ donors. Emergency department triage,
      assessment and admission decisions for patients with intracranial catastrophes
      should consider diagnostic criteria for brain death and recognition of donor
      potential as part of end-of-life care.

PMID- 16803924
TI  - More maneuvers to facilitate tracheal intubation with the GlideScope.

PMID- 16803925
TI  - Indirect vertebral artery injury during cervical spine surgery.

PMID- 16803926
TI  - Postoperative coma in a patient with complete basilar syndrome after anterior
      cervical discectomy.

PMID- 16803927
TI  - Anesthesia for Cesarean delivery in a parturient with rigid spine syndrome.

PMID- 16803928
TI  - University students' perspectives on a physical activity record-keeping log.
AB  - This qualitative study explored characteristics of a record-keeping log that
      students would find appealing and be receptive to using. A heterogeneous sample
      of undergraduate university students aged 18 to 25 years participated. An
      experienced moderator, using a semistructured interview guide, conducted 13 focus
      groups (N = 65). All focus groups were audio-recorded and transcribed verbatim.
      Inductive content analysis was conducted independently by two qualitative
      researchers. Measures were incorporated throughout the study to ensure data
      trustworthiness. Four themes illustrated students' suggestions for the log:
      layout, convenience, maximum distribution, and concerns. In particular, students
      discussed the use of a computer-based versus a paper-based log, hesitancies in
      using a log, and the need for: additional health information, multivenue
      distribution, and low to no cost. Students confirmed that a record-keeping log
      tailored to their needs and preferences would be attractive and appealing to
      students.

PMID- 16803929
TI  - Developing and sustaining community-academic partnerships: lessons from Downstate
      New York Healthy Start.
AB  - Partnering with communities is a critical aspect of contemporary health
      promotion. Linkages between universities and communities are particularly
      significant, given the prominence of academic institutions in channeling grants.
      This article describes the collaboration between a school of public health and
      several community-based organizations on a maternal and infant health grant
      project. The partnership serves as a model for ways in which a university and
      community organizations can interrelate and interact. Central lessons include the
      significance of sharing values and goals, the benefit of drawing on the different
      strengths of each partner, the gap created by the university's institutional
      focus on research rather than service and advocacy, and the strains created by
      power inequities and distribution of funds. A key element of the partnership's
      success is the emphasis on capacity building and colearning. The project
      demonstrates the potential of employing community-academic partnerships as a
      valuable mechanism for implementing community-based health promotion programs.

PMID- 16803930
TI  - Promoting healthy lifestyles in children: a pilot program of be a fit kid.
AB  - Be a Fit Kid is a 12-week program aimed at improving physical activity and
      nutritional habits in children. The physical activity component of the program
      emphasized cardiovascular fitness, flexibility, muscular strength, and bone
      development through running, yoga, jumping, and strength exercises. All
      activities were individualized and noncompetitive. The nutrition component
      focused on current dietary guidelines that emphasize a diet rich in vegetables,
      fruits, unsaturated fats, and whole grains, and low in saturated fat and sugar.
      Following the 12-week intervention, significant improvements were observed in
      body composition, fitness, nutrition knowledge, dietary habits, and in those who
      participated 75% of the time, significant reductions in total cholesterol and
      triglyceride levels were observed. Findings from the pilot trial suggest that
      health promotion programs can be well received by children and may favorably
      alter overweight and the development of adult lifestyle-related diseases.

PMID- 16803931
TI  - Developing a bioterrorism preparedness campaign for veterans: Using focus groups
      to inform materials development.
AB  - In the context of a global war on terrorism experts have focused on the potential
      for a bioterrorist incident to cause widespread health and psychological
      consequences. Preparation is critical to improving the U.S. response to future
      bioterrorist incidents and educating the public is recognized as a vital part of
      this preparedness effort. Under a grant from the U.S. Veterans Health
      Administration (VHA), researchers from a network of VA health care and research
      facilities initiated a program to develop and evaluate educational materials for
      veterans--including those with mental illness. This article describes the results
      of a series of focus groups with three veteran subpopulations of interest to
      characterize their concerns and information needs and summarizes the insights
      gained that helped guide materials development.

PMID- 16803932
TI  - Getting to social action: the Youth Empowerment Strategies (YES!) project.
AB  - This article describes the social action component of the Youth Empowerment
      Strategies (YES!) project funded by the Centers for Disease Control and
      Prevention through its community-based prevention research (CBPR) initiative.
      YES! is designed to promote problem-solving skills, social action, and civic
      participation among underserved elementary and middle school youth. The after
      school program focuses on identifying and building youths' capacities and
      strengths as a means of ultimately decreasing rates of alcohol, tobacco, and
      other drug use and other risky behaviors. The article discusses the conceptual
      models of risk and intervention and factors contributing to successful social
      action work, including group dynamics, intragroup leadership, facilitator skills,
      and school-community contexts. Attention is focused on how the nature of the
      projects themselves played a key role in determining the likelihood of
      experiencing success. Implications and recommendations for other youth-focused
      empowerment education projects are discussed, including the effective use of
      Photovoice in such projects.

PMID- 16803933
TI  - The evolution of an evaluation: a case study using the tribal participatory
      research model.
AB  - This article presents a case study of how the evaluation design for a dating
      violence prevention and/or youth development program for American Indian youth in
      Arizona evolved throughout the project. Particular attention is given to how the
      evaluation design was guided by the tribal participatory research model. A brief
      rationale for the project is presented along with literature on culturally
      competent evaluation and research with American Indians. A description of the
      project and the unique communities in which it was implemented is provided. The
      focus of the article is the process of how the evaluation plan changed and how
      various factors influenced this process (e.g., feedback from community
      stakeholders, conversations with funder, results of process evaluation,
      suggestions from literature, the authors' experience working in American Indian
      communities). The authors conclude with lessons learned for others to consider as
      they develop working relationships and evaluation plans in similar communities.

PMID- 16803934
TI  - The effectiveness of a multimedia program to prevent fetal alcohol syndrome.
AB  - Fetal alcohol syndrome (FAS) continues to be the leading preventable cause of
      mental retardation in the United States. Because abstaining from alcohol prior to
      and throughout pregnancy is the only way to prevent FAS, some prevention programs
      try to target women before they become pregnant. The Fetal Alcohol Spectrum
      Teaching and Research Awareness Campaign (FASTRAC) is a multimedia, peer
      delivered educational presentation designed to reduce the incidence of FAS.
      Results from an ethnically diverse sample of high school students indicate that
      the program increased participants' knowledge regarding FAS but had no
      significant effect on participants' attitudes, beliefs about the dangers of FAS
      or intention to use alcohol during pregnancy. The FASTRAC program failed partly
      because of its didactic approach and the lack of health education principles that
      have been shown to be effective in changing other substance use behaviors.
      Suggestions for improving FAS prevention education programs are offered.

PMID- 16803935
TI  - PREMIER--a trial of lifestyle interventions for blood pressure control:
      intervention design and rationale.
AB  - Interventions encouraging adoption of healthy diets and increased physical
      activity are needed to achieve national goals for preventing and treating
      hypertension, cardiovascular disease, diabetes, and other chronic diseases.
      PREMIER was a multicenter clinical trial testing the effects of two lifestyle
      interventions on blood pressure control, compared with advice only. Both
      interventions implemented established national guidelines for blood pressure
      control (weight loss, reduced sodium and alcohol intake, and increased physical
      activity), and one intervention also included the Dietary Approaches to Stop
      Hypertension (DASH) diet. Both interventions focused on behavioral self
      management, motivational enhancement, and personalized feedback. This article
      describes the design and evaluation approaches for these interventions.
      Evaluation of multicomponent lifestyle change interventions can help us
      understand the benefits and difficulties of making multiple lifestyle changes
      concurrently and the effects such changes can have on blood pressure,
      particularly in minorities at higher risk for hypertension.

PMID- 16803936
TI  - Diagnostic accuracy of tissue Doppler echocardiography for patients with acute
      heart failure.
AB  - BACKGROUND: Acute heart failure leads to high mortality and morbidity rates. The
      symptom of acute dyspnoea is non-specific and the diagnostic tools of acute heart
      failure are still not satisfactory. Tissue Doppler echocardiography is accurate
      in evaluating cardiac function; however, its efficacy in diagnosing patients with
      acute dyspnoea in emergency departments remains unclear. METHODS: Patients with
      acute dyspnoea were included prospectively while visiting the emergency
      department. Tissue Doppler echocardiography was carried out and the ratios of
      peak early diastolic transmitral blood flow velocity (E) to the peak early
      diastolic tissue velocity over mitral annulus (Ea) were recorded. The
      sensitivity, specificity and accuracy of tissue Doppler parameters and the
      receiver-operating characteristic curves for diagnosing acute heart failure were
      also evaluated. RESULTS: A total of 92 patients were enrolled. The ratio E:Ea was
      found to be a good diagnostic test to estimate the diagnostic performances of
      tissue Doppler echocardiography using receiver-operating characteristic curves in
      cases of acute heart failure in patients with preserved left ventricular systolic
      function (mean (SD) area under the curve = 0.875 (0.049); p<0.001; cut-off value
      = 11) and with left ventricular systolic dysfunction (mean (SD) area under the
      curve = 0.903 (0.061); p = 0.003; cut-off value = 16). E:Ea was an independent
      predictor of acute heart failure in multiple logistic regressions. For patients
      with a B-type natriuretic peptide level between 100 and 500 pg/ml, E:Ea provided
      an accuracy of 90.9% (p = 0.015) for diagnosing acute heart failure. CONCLUSIONS:
      Tissue Doppler echocardiography is accurate in diagnosing patients with acute
      heart failure in emergency departments. It can be a useful supplementary
      diagnostic tool for patients with inconclusive blood B-type natriuretic peptide
      level.

PMID- 16803937
TI  - Left ventricular growth response to exercise and cigarette smoking: data from
      LARGE Heart.
AB  - BACKGROUND: Increasing left ventricular mass is a risk factor for cardiovascular
      morbidity and mortality. OBJECTIVE: To examine the possible association of
      smoking with the left ventricular growth response in men. METHODS: Left
      ventricular mass was measured in 309 army recruits before and after an identical
      12-week physical training programme. Left ventricular mass was determined using
      cardiovascular magnetic resonance. RESULTS: Left ventricular mass increased with
      training (mean (standard deviation (SD)) 3.83 (10.81) g, p<0.001). By univariate
      analysis, exercise-induced change in left ventricular mass was positively
      associated with cigarette smoking (mean (SD) 1.69 (11.10) g v 4.76 (10.23) g for
      non-smokers v ex- and current smokers, respectively; p = 0.026), whereas age,
      height, diastolic and systolic blood pressure (SBP), alcohol consumption or
      indices of physical activity were not significantly associated with change in
      left ventricular mass. Multivariate analysis showed body weight, smoking status
      and SBP to be independent predictors of left ventricular mass (incremental R(2) =
      3.4%, p = 0.004; R(2) = 4.9%, p = 0.024; and R(2) = 1.7%, p = 0.041,
      respectively). CONCLUSIONS: Cigarette smoking and SBP are associated with
      exercise-induced left ventricular growth in young men. The positive association
      of smoking with changes in left ventricular mass is surprising, given the limited
      exposure of these subjects to smoking, and although these data do not prove
      causation, they are of great interest to those trying to uncover the drivers of
      left ventricular hypertrophy, as well as to those examining the possible ill
      effects of smoking in the young.

PMID- 16803938
TI  - Embolic and bleeding events after modified Bentall procedure in selected
      patients.
AB  - AIM: As valve-sparing procedures gain increasing popularity, the long-term
      results of the total aortic root replacement (TARR) were evaluated using
      mechanical valve grafts in selected patients. METHODS AND RESULTS: From January
      1993 to December 2003, 100 patients (87 men), aged >65 years (mean 51 (SD 10.4
      years), presenting with isolated aortic root dilatation with or without aortic
      valve insufficiency, undergoing elective root replacement using a mechanical
      valve graft were reviewed. The aetiology of aortic root disease was degenerative
      in 69 patients and related to the bicuspid aortic valve in 31 patients. In 11
      patients, concomitant coronary artery bypass graft was performed. Hospital
      mortality was 4%. Overall survival was 93.9% (2.4%), 89.1% (3.5%) and 83.2%
      (5.2%) at 1, 5 and 7 years, respectively. 14 patients experienced 45 embolic
      events (3.21 (2.64) events/patient; range: 1-10 events). Thus, the linearised
      rate of embolic events was 10.3 per 100 patient-years (95% confidence interval
      (CI) 7.29 to 13.31). The actuarial embolism-free survival was 96.6% (1.9%), 77.1%
      (6%) and 74.3% (6.4%) at 1, 5 and 7 years, respectively. The linearised rate of
      bleeding events was 2.2 per 100 patient-years (95% CI 0.87 to 3.71). Actuarial
      bleeding free survival was 95.6% (2.1%), 93.2% (2.6%) and 87.7% (5.8%) at 1, 5
      and 7 years. respectively. None of the patients required reoperation and no cases
      of structural or non-structural valve dysfunction were observed. CONCLUSIONS:
      TARR using mechanical valve grafts yields excellent survival results in selected
      patients. However, a high rate of minor thromboembolic events was recorded.
      Aspirin in combination with oral anticoagulants might be of potential interest in
      these patients.

PMID- 16803939
TI  - Microvascular perfusion 1 week and 6 months after myocardial infarction by first
      pass perfusion cardiovascular magnetic resonance imaging.
AB  - OBJECTIVE: To characterise the evolution of myocardial perfusion during the first
      6 months after myocardial infarction by first-pass perfusion cardiovascular
      magnetic resonance imaging (CMR) and determine its significance. DESIGN:
      Prospective cohort design. SETTING: Single-centre study in a teaching hospital in
      Spain. PATIENTS: 40 patients with a first ST-elevation myocardial infarction,
      single-vessel disease and thrombolysis in myocardial infarction (TIMI) grade 3
      flow (stent in 33 patients) underwent rest and low-dose dobutamine CMR 7 (SD 1)
      and 184 (SD 11) days after infarction. Microvascular perfusion was assessed at
      rest by visual assessment and quantitative analysis of first-pass perfusion CMR.
      Of the 640 segments, 290 segments subtended by the infarct-related artery (IRA)
      were focused on. RESULTS: Both 1 week and 6 months after infarction, segments
      with normal perfusion showed more wall thickening, contractile reserve and wall
      thickness, and less transmural necrosis, p <0.05 in all cases. Of 76 hypoperfused
      segments at the first week, 47 (62%) normalised perfusion at the sixth month.
      However, 42 segments (14% of the whole group) showed chronic abnormal perfusion;
      these segments showed worse CMR indices in the late phase (p<0.05 in all cases).
      CONCLUSIONS: In patients with an open IRA, more than half of the segments with
      abnormal perfusion at the first week are normally perfused after six months.
      First-pass perfusion CMR shows that in a small percentage of segments, abnormal
      perfusion may become a chronic phenomenon-these areas have a more severe
      deterioration of systolic function, wall thickness, contractile reserve and the
      transmural extent of necrosis.

PMID- 16803940
TI  - Comparison of the haemodynamics of different pacing sites in patients undergoing
      resynchronisation treatment: need for individualisation of lead localisation.
AB  - BACKGROUND: Biventricular pacing is a new therapy for the treatment of heart
      failure. However, a substantial number of patients do not respond to this
      therapy. HYPOTHESIS: Individually determined maximal pacing sites will improve
      the haemodynamic response and increase the number of responders. METHODS: In 48
      patients with heart failure, the acute haemodynamic effects of nine different
      pacing configurations were studied, using two right and left ventricular pacing
      sites and their combinations. Cardiac index was measured using Doppler
      echocardiography. For further analysis, the combination with the highest cardiac
      index improvement was compared with baseline. Moreover, the number of responders
      was calculated using a cut-off value of 10% increase in cardiac index. RESULTS:
      The mean (SD) increase in cardiac index ranged between 3.8% (6.0%) and 11.1%
      (8.6%). The pacing site with maximal cardiac index was highly variable between
      patients, and here the cardiac index increased to 14.8% (7.6%; (p<0.001). The
      number of responders varied between 15% and 64%, increasing to 75% at the site
      with maximal increase in cardiac index. In a subset of patients, the haemodynamic
      improvement after pacemaker implantation correlated well with the acute
      haemodynamics. CONCLUSION: Individualisation of pacing configuration for
      biventricular pacing leads to further haemodynamic improvement in patients with
      heart failure and reduces the number of patients not responding to this therapy.

PMID- 16803941
TI  - Improving women's experience during speculum examinations at routine
      gynaecological visits: randomised clinical trial.
AB  - OBJECTIVES: To determine if a standardised method of leg positioning without
      stirrups reduces the physical discomfort and sense of vulnerability and increases
      the sense of control among women undergoing speculum examination as part of a
      routine gynaecological examination. DESIGN: Randomised clinical trial. SETTING:
      Family medicine outpatient clinic. PATIENTS: 197 adult women undergoing routine
      gynaecological examination and cervical smear. INTERVENTION: Examination with or
      without stirrups. MAIN OUTCOME MEASURES: Women's perceived levels of physical
      discomfort, sense of vulnerability, and sense of control during the examination,
      measured on 100 mm visual analogue scales. RESULTS: Women undergoing examination
      without stirrups had a reduction in mean sense of vulnerability from 23.6 to 13.1
      (95% confidence interval of the difference - 16.6 to - 4.4). Mean physical
      discomfort was reduced from 30.4 to 17.2 (- 19.7 to - 6.8). There was no
      significant reduction in sense of loss of control. CONCLUSION: Women should be
      able to have gynaecological examinations without using stirrups to reduce the
      stress associated with speculum examinations. TRIAL REGISTRATION: US Army Central
      Investigation Regulatory Office. Trial No DDEAMC 05-11.

PMID- 16803942
TI  - Psychological interventions to improve glycaemic control in patients with type 1
      diabetes: systematic review and meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To determine whether psychological interventions have any effect on
      glycaemic control in people with type 1 diabetes. DESIGN: Systematic review and
      meta-analysis of psychological therapies to assess their effectiveness in
      improving glycaemic control in type 1 diabetes. DATA SOURCES: Medline, PsycINFO,
      Embase, and Cochrane central register of controlled trials searched to September
      2004. REVIEW METHODS: All included studies were randomised controlled trials in
      children (including adolescents) or adults with type 1 diabetes that evaluated
      the effect of a psychological therapy (counselling, cognitive behaviour therapy,
      family systems therapy, and psychodynamic therapy) on control of diabetes. Data
      were extracted on sample size, age, duration of diabetes, type of psychological
      therapy, its mode of delivery, and type of intervention in control group. MAIN
      OUTCOME MEASURES: Glycaemic control measured by percentage of glycated
      haemoglobin and psychological distress. Pooled standardised effect sizes were
      calculated. RESULTS: 29 trials were eligible for the systematic review and 21
      trials for the meta-analysis. In the 10 studies of children and adolescents
      included in the meta-analysis, the mean percentage of glycated haemoglobin was
      significantly reduced in those who had received a psychological intervention
      compared with those in the control group (pooled standardised mean difference 
      0.35 (95% confidence interval -0.66 to -0.04), equivalent to a 0.48% (0.05% to
      0.91%) absolute reduction in glycated haemoglobin. In the 11 studies in adults
      the pooled standardised mean difference was -0.17 (-0.45 to 0.10), equivalent to
      0.22% (-0.13% to 0.56%) absolute reduction in glycated haemoglobin. Psychological
      distress was significantly lower in the intervention groups in children and
      adolescents (pooled standardised effect size -0.46, -0.83 to -0.10) but not in
      adults (-0.25, -0.51 to 0.01). CONCLUSION: Psychological treatments can slightly
      improve glycaemic control in children and adolescents with diabetes but have no
      effect in adults.

PMID- 16803944
TI  - Defined by publication: a commentary on health education and health promotion
      publication trends.

PMID- 16803943
TI  - Reliability of self reported form of female genital mutilation and WHO
      classification: cross sectional study.
AB  - OBJECTIVE: To assess the reliability of self reported form of female genital
      mutilation (FGM) and to compare the extent of cutting verified by clinical
      examination with the corresponding World Health Organization classification.
      DESIGN: Cross sectional study. SETTINGS: One paediatric hospital and one
      gynaecological outpatient clinic in Khartoum, Sudan, 2003-4. PARTICIPANTS: 255
      girls aged 4-9 and 282 women aged 17-35. MAIN OUTCOME MEASURES: The women's
      reports of FGMthe actual anatomical extent of the mutilation, and the
      corresponding types according to the WHO classification. RESULTS: All girls and
      women reported to have undergone FGM had this verified by genital inspection.
      None of those who said they had not undergone FGM were found to have it. Many
      said to have undergone "sunna circumcision" (excision of prepuce and part or all
      of clitoris, equivalent to WHO type I) had a form of FGM extending beyond the
      clitoris (10/23 (43%) girls and 20/35 (57%) women). Of those who said they had
      undergone this form, nine girls (39%) and 19 women (54%) actually had WHO type
      III (infibulation and excision of part or all of external genitalia). The
      anatomical extent of forms classified as WHO type III varies widely. In 12/32
      girls (38%) and 27/245 women (11%) classified as having WHO type III, the labia
      majora were not involved. Thus there is a substantial overlap, in an anatomical
      sense, between WHO types II and III. CONCLUSION: The reliability of reported form
      of FGM is low. There is considerable under-reporting of the extent. The WHO
      classification fails to relate the defined forms to the severity of the
      operation. It is important to be aware of these aspects in the conduct and
      interpretation of epidemiological and clinical studies. WHO should revise its
      classification.

PMID- 16803945
TI  - What is quality in surgical pathology?
AB  - Quality in surgical pathology may be defined as accurate, timely, and complete
      reports. Achieving quality requires substantial investment in the basic structure
      and in the people who undertake surgical pathology. Quality assurance and
      improvement works best when it is woven into the systems of surgical pathology
      with well informed, well trained, and knowledgeable staff.

PMID- 16803947
TI  - My approach to internal quality control in a clinical immunology laboratory.

PMID- 16803949
TI  - Diagnostic accuracy of core biopsy for ductal carcinoma in situ and its
      implications for surgical practice.
AB  - BACKGROUND: Core biopsy is considered to be a highly accurate method of gaining a
      preoperative histological diagnosis of breast cancer. Ductal carcinoma in situ
      (DCIS) is often impalpable and is a more subtle form of breast cancer. AIM: To
      investigate the accuracy of core biopsy in the diagnosis of cancer in patients
      with DCIS. METHODS: All patients who had invasive cancer (n = 959) or DCIS (n =
      92) that was confirmed by excision between 1999 and 2004 were identified. The
      diagnostic methods, histology of the core biopsy specimen and excision histology
      were reviewed in detail. RESULTS: Core biopsy was attempted in 88% (81/92) of
      patients with DCIS and in 91% (874/959) of those with invasive disease. Of those
      patients who underwent core biopsy, a diagnosis of carcinoma on the initial core
      was made in 65% (53/81) of patients with DCIS compared with 92% (800/874) of
      patients with invasive disease (p<0.0001). Smaller lesion size (p = 0.005) and
      lower grade (p = 0.03) were associated with increased risk for a negative or non
      diagnostic core in patients with DCIS. The nature of the mammographic lesion or
      the method of biopsy did not affect the probability of an accurate core biopsy.
      Patients who had a preoperative diagnosis of DCIS by core biopsy had a
      reoperation rate of 36% compared with 65% of those that did not have a
      preoperative diagnosis (p = 0.007). CONCLUSION: Although core biopsies are highly
      accurate forms of obtaining a preoperative diagnosis in patients with invasive
      breast cancer, this is not the case in DCIS. As the number of surgical procedures
      can be reduced by core biopsy, it is still of considerable value in the
      management of DCIS.

PMID- 16803948
TI  - Prognostic significance of CDC25B expression in gliomas.
AB  - BACKGROUND: CDC25B is a cell-cycle regulatory protein, which is considered to be
      related to tumorigenesis and progression of tumours. AIMS: To elucidate the role
      of CDC25B in glioma, the expression of CDC25B and the association of the CDC25B
      expression with the clinicopathological parameters were investigated. METHODS:
      Fifty seven gliomas, which included 21 low-grade astrocytomas, 17 anaplastic
      astrocytomas and 19 glioblastomas, were studied. Protein expressions of CDC25B
      were evaluated by immunohistochemical methods. Semiquantitative and real-time RT
      PCR analyses for the expression of CDC25B mRNA were also carried out. Disease
      free survival (DFS) data were analysed by using the Kaplan-Meier method. RESULTS:
      High expression of CDC25B was identified in 18 of the 19 glioblastomas, in 10 of
      the 17 anaplastic astrocytomas, but not in any of the 21 low-grade astrocytomas.
      The CDC25B mRNA expression increased with the rise in histological grade.
      Increased CDC25B expression was correlated significantly with a shorter period of
      DFS, as shown by multivariate analysis. CONCLUSIONS: Patients with an
      unfavourable clinical outcome are characterised by the increased expression of
      CDC25B in their glioma samples. Useful clinical information, especially on its
      relevance as a prognostic indicator, is provided by the evaluation of CDC25B
      expression in gliomas.

PMID- 16803951
TI  - Malignant histiocytosis: a case report of a rare tumour presenting with
      spontaneous splenic rupture.
AB  - Malignant histiocytosis is a rare invasive proliferation of neoplastic
      histiocytes. Cases previously reported as malignant histiocytosis were shown to
      be lymphomas of T or B lineage, especially anaplastic large-cell lymphomas. A
      case of malignant histiocytosis is described, in which a patient presenting with
      symptoms suggestive of pneumonia suddenly deteriorated and died. At autopsy, a
      large quantity of fresh blood, originating from several ruptured nodules on the
      enlarged spleen, was seen in the peritoneal cavity. Extensive infiltration by
      pleomorphic tumour cells and erythrophagocytosis by tumour cells were seen on
      histological examination of the spleen. Immunohistochemical analysis and staining
      were carried out. This is the second reported case of malignant histiocytosis
      presenting with spontaneous splenic rupture.

PMID- 16803950
TI  - Audit of laboratory mycology services for the management of patients with fungal
      infections in the northwest of England.
AB  - BACKGROUND: Fungal infection is increasingly recognised as an important cause of
      morbidity and mortality, especially in immunocompromised patients. Little
      information exists on laboratory services available and the methods used by
      general microbiology laboratories to diagnose these important infections. AIM: To
      investigate the services microbiology laboratories in northwest England provide
      towards the diagnosis and management of superficial and deep fungal infections.
      METHODS: A questionnaire was sent to laboratories to get a holistic view of the
      support given to clinicians looking after patients with fungal infections. The
      aim was not to investigate details of each laboratory's standard operating
      procedures. The completed questionnaires, which formed the basis of this report,
      were returned by all 21 laboratories which were recruited. This study was
      conducted between March 2004 and September 2004. RESULTS: Services were provided
      to District General Hospitals and to six tertiary centres, including eight
      teaching hospitals by 16 laboratories. Their bed capacity was 250-1300 beds.
      Total specimens (including bacterial and viral) processed annually were 42 000
      500,000 whereas fungal ones were 560-5400. CONCLUSION: In most microbiology
      laboratories of northwest England, clinicians were aware of the potential of
      fungal pathogens to cause infections especially in immunocompromised patients.
      Additional measures such as prolonged incubation of samples were introduced to
      improve fungal yield from patients at high risk. It is necessary to train and
      educate laboratory and medical staff about the role of serology and molecular
      methods in diagnosis and management of patients with fungal infection.

PMID- 16803946
TI  - My approach to performing a perinatal or neonatal autopsy.
AB  - An opportunity to determine the cause of death, factors that may have a role in
      it, and the extent and cause of malformations is provided by perinatal autopsy.
      The family may be assisted in finding closure after the death of their infant by
      the information obtained. Insight into classifying infants appearing normal into
      one of three groups, small, appropriate and large for gestational age, has been
      provided, as each group tends to have specific causes of death. In infants with
      congenital anomalies, patterns of malformation may lead us to the diagnosis. An
      accurate diagnosis is required to provide counselling for a subsequent pregnancy.

PMID- 16803952
TI  - Isolated haploinsufficiency of exon 1 of the SHOX gene in a patient with
      idiopathic short stature.
AB  - This paper reports the case of a 16-year-old woman with idiopathic short stature
      (ISS) who was detected to be haploinsufficient in only exon 1 of the short
      stature homeobox-containing (SHOX) gene by RQ-PCR and had two copies of the other
      six exons intact. The translation of the SHOX protein and of the SHOX promoter
      may be potentially affected if the deletion of exon 1 is extended further
      upstream. Further studies may help in determining the significance of partial
      exonic deletions of the SHOX gene in relation to ISS.

PMID- 16803953
TI  - Primary primitive neuroectodermal tumour of the urinary bladder: a clinico
      pathological study emphasising immunohistochemical, ultrastructural and molecular
      analyses.
AB  - Primary primitive neuroectodermal tumours (PNETs) of the bladder are extremely
      rare and aggressive neoplasms, and only six examples have been reported in the
      literature. The case of a 21-year-old woman, who remains disease free 3 years
      after tumour resection, is reported here. Morphological features were found to
      correspond to a small round blue cell tumour without rosette formation and with
      extensive areas of necrosis. Strong expression of CD99, vimentin and CD117 (c
      kit), and focal reactivity to cytokeratin and S-100 protein was observed in
      tumour cells. Ultrastructurally, sparse neurosecretory granules were observed.
      Diagnosis of PNET was supported by molecular genetic analysis, showing the EWS
      FLI-1 fusion transcript type 2 by RT-PCR and EWS gene rearrangement by
      fluorescence in situ hybridisation. A normal genetically balanced genotype was
      shown by comparative genomic hybridisation, which, together with the expression
      of c-kit, a known therapeutic target for imatinib, may have prognostic and
      therapeutic implications.

PMID- 16803954
TI  - Bilateral multiple axillary apocrine hidrocystomas associated with benign
      apocrine hyperplasia.

PMID- 16803955
TI  - Striking male predominance of mantle cell lymphoma in Taiwan.

PMID- 16803957
TI  - Green primary explosives: 5-nitrotetrazolato-N2-ferrate hierarchies.
AB  - The sensitive explosives used in initiating devices like primers and detonators
      are called primary explosives. Successful detonations of secondary explosives are
      accomplished by suitable sources of initiation energy that is transmitted
      directly from the primaries or through secondary explosive boosters. Reliable
      initiating mechanisms are available in numerous forms of primers and detonators
      depending upon the nature of the secondary explosives. The technology of
      initiation devices used for military and civilian purposes continues to expand
      owing to variations in initiating method, chemical composition, quantity,
      sensitivity, explosive performance, and other necessary built-in mechanisms.
      Although the most widely used primaries contain toxic lead azide and lead
      styphnate, mixtures of thermally unstable primaries, like diazodinitrophenol and
      tetracene, or poisonous agents, like antimony sulfide and barium nitrate, are
      also used. Novel environmentally friendly primary explosives are expanded here to
      include cat[Fe(II)(NT)(3)(H(2)O)(3)], cat(2)[Fe(II)(NT)(4)(H(2)O)(2)],
      cat(3)[Fe(II)(NT)(5)(H(2)O)], and cat(4)[Fe(II)(NT)(6)] with cat = cation and NT(
      ) = 5-nitrotetrazolato-N(2). With available alkaline, alkaline earth, and organic
      cations as partners, four series of 5-nitrotetrazolato-N(2)-ferrate hierarchies
      have been prepared that provide a plethora of green primaries with diverse
      initiating sensitivity and explosive performance. They hold great promise for
      replacing not only toxic lead primaries but also thermally unstable primaries and
      poisonous agents. Strategies are also described for the systematic preparation of
      coordination complex green primaries based on appropriate selection of ligands,
      metals, and synthetic procedures. These strategies allow for maximum versatility
      in initiating sensitivity and explosive performance while retaining properties
      required for green primaries.

PMID- 16803956
TI  - The QseC sensor kinase: a bacterial adrenergic receptor.
AB  - Quorum sensing is a cell-to-cell signaling mechanism in which bacteria respond to
      hormone-like molecules called autoinducers (AIs). The AI-3 quorum-sensing system
      is also involved in interkingdom signaling with the eukaryotic hormones
      epinephrine/norepinephrine. This signaling activates transcription of virulence
      genes in enterohemorrhagic Escherichia coli O157:H7. However, this signaling
      system has never been shown to be involved in virulence in vivo, and the
      bacterial receptor for these signals had not been identified. Here, we show that
      the QseC sensor kinase is a bacterial receptor for the host
      epinephrine/norepinephrine and the AI-3 produced by the gastrointestinal
      microbial flora. We also found that an alpha-adrenergic antagonist can
      specifically block the QseC response to these signals. Furthermore, we
      demonstrated that a qseC mutant is attenuated for virulence in a rabbit animal
      model, underscoring the importance of this signaling system in virulence in vivo.
      Finally, an in silico search found that the periplasmic sensing domain of QseC is
      conserved among several bacterial species. Thus, QseC is a bacterial adrenergic
      receptor that activates virulence genes in response to interkingdom cross
      signaling. We anticipate that these studies will be a starting point in
      understanding bacterial-host hormone signaling at the biochemical level. Given
      the role that this system plays in bacterial virulence, further characterization
      of this unique signaling mechanism may be important for developing novel classes
      of antimicrobials.

PMID- 16803958
TI  - The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a
      paired amphipathic helix-like TBP-associated factor homology domain.
AB  - Up to 15% of acute myeloid leukemias (AMLs) are characterized by the abnormal
      expression of the eight-twenty-one (ETO) transcriptional corepressor within an
      AML1-ETO fusion protein. The t(8;21) chromosomal translocation serves not only to
      disrupt WT AML1 function but also to introduce ETO activity during hematopoiesis.
      AML1-ETO was recently shown to inhibit E protein transactivation by physically
      displacing WT coactivator proteins in an interaction mediated by ETO. Here, we
      present the 3D solution structure of the human ETO TAFH (eTAFH) domain implicated
      in AML1-ETO:E protein interactions and report an unexpected fold similarity to
      paired amphipathic helix domains from the transcriptional corepressor Sin3. We
      identify and characterize a conserved surface on eTAFH that is essential for
      ETO:E protein recognition and show that the mutation of key conserved residues at
      this site alleviates ETO-based silencing of E protein transactivation. Our
      results address uncharacterized aspects of the corepression mechanism of ETO and
      suggest that eTAFH may serve to recruit ETO (or AML1-ETO) to DNA-bound
      transcription factors. Together, these findings imply that a cofactor exchange
      mechanism, analogous to that described for E protein inhibition, may represent a
      common mode of action for ETO.

PMID- 16803960
TI  - RNAi-mediated silencing of estrogen receptor {alpha} in the ventromedial nucleus
      of hypothalamus abolishes female sexual behaviors.
AB  - Estrogen receptor alpha (ERalpha) plays a major role in the regulation of
      neuroendocrine functions and behaviors by estrogens. Although the generation of
      ERalpha knockout mice advanced our knowledge of ERalpha functions, gene deletion
      using this method is global and potentially confounded by developmental
      consequences. To achieve a site-specific knockdown of ERalpha in the normally
      developed adult brain, we have generated an adeno-associated virus vector
      expressing a small hairpin RNA targeting ERalpha. After bilateral injection of
      this vector into the hypothalamic ventromedial nucleus in ovariectomized female
      mice, expression levels of ERalpha as well as the estrogen-inducible progesterone
      receptor were profoundly reduced despite the continued presence of this receptor
      elsewhere in the brain. Functionally, silencing of ERalpha in the ventromedial
      nucleus abolished female proceptive and receptive sexual behaviors while
      enhancing rejection behavior. These results provide evidence that adeno
      associated virus-mediated long-term knockdown of genes can be used to delineate
      their effects on complex behaviors in discrete brain regions.

PMID- 16803959
TI  - Variants in the SP110 gene are associated with genetic susceptibility to
      tuberculosis in West Africa.
AB  - The sst1 locus has been identified in a mouse model to control resistance and
      susceptibility of Mycobacterium tuberculosis infection. Subsequent studies have
      now identified Ipr1 (intracellular pathogen resistance 1) to be the gene
      responsible. Ipr1 is encoded within the sst1 locus and is expressed in the
      tuberculosis lung lesions and macrophages of sst1-resistant, but not sst1
      susceptible mice. We have therefore examined the closest human homologue of Ipr1,
      SP110, for its ability to control susceptibility to M. tuberculosis infection in
      humans. In a study of families from The Gambia we have identified three
      polymorphisms that are associated with disease. On examination of additional
      families from Guinea-Bissau and the Republic of Guinea, two of these associations
      were independently replicated. These variants are in strong linkage
      disequilibrium with each other and lie within a 31-kb block of low haplotypic
      diversity, suggesting that a polymorphism within this region has a role in
      genetic susceptibility to tuberculosis in humans.

PMID- 16803961
TI  - Primary processes underlying the photostability of isolated DNA bases: adenine.
AB  - The UV chromophores in DNA are the nucleic bases themselves, and it is their
      photophysics and photochemistry that govern the intrinsic photostability of DNA.
      Because stability is related to the conversion of dangerous electronic to less
      dangerous vibrational energy, we study ultrafast electronic relaxation processes
      in the DNA base adenine. We excite adenine, isolated in a molecular beam, to its
      pipi* state and follow its relaxation dynamics using femtosecond time-resolved
      photoelectron spectroscopy. To discern which processes are important on which
      timescales, we compare adenine with 9-methyl adenine. Methylation blocks the site
      of the much-discussed pisigma* state that had been thought, until now, minor.
      Time-resolved photoelectron spectroscopy reveals that, although adenine and 9
      methyl adenine show almost identical timescales for the processes involved, the
      decay pathways are quite different. Importantly, we confirm that in adenine at
      267-nm excitation, the pisigma* state plays a major role. We discuss these
      results in the context of recent experimental and theoretical studies on adenine,
      proposing a model that accounts for all known results, and consider the
      relationship between these studies and electron-induced damage in DNA.

PMID- 16803963
TI  - Profile of William D. Nordhaus.

PMID- 16803964
TI  - Aging is no longer an unsolved problem in biology.
AB  - For much of the 20th century, the accumulation of a considerable amount of
      information about the processes of aging did not reveal the underlying
      mechanisms. Toward the end of that century, the biological basis for aging became
      very much clearer. It became apparent that the best strategy for animals'
      survival was to develop to an adult, but not to invest resources in maintaining
      the body, or soma, indefinitely. In their natural environment, animals do not
      survive environmental hazards (predators, disease, starvation, and drought) to
      reach a long life span. There is thus a trade-off between the investment of
      resources in reproduction, and the survival time of the soma. At a stroke, this
      solves the problem of different rates of aging in different species, because
      those that develop and reproduce fast also have short life spans, and those that
      develop and reproduce slowly have long life spans. This difference is due to
      actual resources invested in the maintenance of the adult soma. There is now much
      evidence that long-lived mammals have much more efficient maintenance mechanisms
      than short-lived mammals. Thus, aging can be defined as the eventual failure of
      maintenance. It also became apparent that many different maintenance mechanisms
      exist, and that these depend on very many genes and a considerable investment in
      metabolic resources. Most individual theories of aging revolve around the failure
      of a given maintenance system, but as there are many of these, it is likely that
      most of the important theories have some degree of truth. A broad interpretation
      of the different degenerative changes during senescence should therefore be
      adopted, with the major conclusion that aging is multicausal. It is also evident
      that the evolved design of many components of complex animals is incompatible
      with indefinite survival. We can therefore conclude that this evolved design is
      intrinsically related to the fact of aging. This in turn means that aging cannot
      be reversed, although it may be modulated, as, for example, by calorie
      restriction.

PMID- 16803962
TI  - The C2H2 zinc-finger protein SYD-9 is a putative posttranscriptional regulator
      for synaptic transmission.
AB  - Communication between neurons is largely achieved through chemical synapses,
      where neurotransmitters are released from synaptic vesicles at presynaptic
      terminals to activate postsynaptic cells. Exo- and endocytosis are coordinated to
      replenish the synaptic vesicle pool for sustained neuronal activity. We
      identified syd-9 (syd, synapse defective), a gene that encodes multiple C2H2 zinc
      finger domain-containing proteins specifically required for synaptic function in
      Caenorhabditis elegans. syd-9 loss-of-function mutants exhibit locomotory
      defects, a diffuse distribution of synaptic proteins, and decreased synaptic
      transmission with unaffected neurodevelopment. syd-9 mutants share phenotypic and
      ultrastructural characteristics with mutants that lack synaptic proteins that are
      required for endocytosis. syd-9 mutants also display genetic interactions with
      these endocytotic mutants, suggesting that SYD-9 regulates endocytosis. SYD-9
      proteins are enriched in the nuclei of both neuron and muscle cells, but their
      neuronal expression plays a major role in locomotion. SYD-9 isoforms display a
      speckle-like expression pattern that is typical of RNA-binding proteins that
      regulate premRNA splicing. Furthermore, syd-9 functions in parallel with unc-75
      (unc, uncoordinated), the C. elegans homologue of the CELF/BrunoL family protein
      that regulates mRNA alternative splicing and processing, and is also required
      specifically for synaptic transmission. We propose that neuronal SYD-9 proteins
      are previously uncharacterized and specific posttranscriptional regulators of
      synaptic vesicle endocytosis.

PMID- 16803965
TI  - Free radical theory of aging: an update: increasing the functional life span.
AB  - Aging is the progressive accumulation of diverse, deleterious changes with time
      that increase the chance of disease and death. The basic chemical process
      underlying aging was first advanced by the free radical theory of aging (FRTA) in
      1954: the reaction of active free radicals, normally produced in the organisms,
      with cellular constituents initiates the changes associated with aging. The
      involvement of free radicals in aging is related to their key role in the origin
      and evolution of life. Aging changes are commonly attributed to development,
      genetic defects, the environment, disease, and an inborn aging process (IAP). The
      latter produces aging changes at an exponentially increasing rate with age,
      becoming the major risk factor for disease and death for humans after the age of
      28 years in the developed countries. In them the IAP limits human average life
      expectancy at birth (ALE-B)--a rough measure of the healthy life span--to about
      85 years; few reach 100 years and only one is known to have lived to 122 years.
      In these countries, improvements in living conditions (ILC) have gradually raised
      ALE-Bs to 76-79 years, 6-9 years less than the limit imposed by aging, with no
      change in the maximum life span (MLS). The extensive studies based on the FRTA
      hold promise that ALE-B and the MLS can be extended, the ALE-B possibly by a few
      years, and the MLS somewhat less.

PMID- 16803966
TI  - The free radical fantasy: a panoply of paradoxes.
AB  - Overly exuberant and exaggerated past expectations and claims of the free radical
      theory have been quieted by extensive randomized, double-blind, controlled human
      studies. A half century of data demonstrates its lack of predictability and it
      has not been validated by the scientific method. Widespread use of antioxidants
      has failed to quell the current pandemic of cancer, diabetes, and cardiovascular
      disease or to stop or reverse the aging process. Electronically modified oxygen
      derivatives contribute to the modulation of cellular redox status, which is of
      primary importance in disease prevention and homeostasis.

PMID- 16803967
TI  - Catabolic insufficiency and aging.
AB  - Cellular degradative processes, which include lysosomal (autophagic) and
      proteasomal degradation, as well as the activity of cytosolic and mitochondrial
      proteases, provide for a continuous turnover of damaged and obsolete biomolecules
      and organelles. Inherent insufficiency of these degradative processes results in
      progressive accumulation within long-lived postmitotic cells of biological
      "garbage" ("waste" material), such as indigestible protein aggregates, defective
      mitochondria, and lipofuscin (age pigment), an intralysosomal, polymeric,
      undegradable material. Intracellular "garbage" is neither completely catabolized,
      nor exocytosed to any considerable extent. Heavy lipofuscin loading of lysosomes,
      typical of old age, seems to pronouncedly decrease autophagic potential. As
      postulated in the mitochondrial-lysosomal axis theory of aging, this occurs on
      account of the transport of newly synthesized lysosomal enzymes to lipofuscin
      loaded lysosomes rather than to active lysosomes/late endosomes, making the
      enzyme content of autophagolysosomes insufficient for proper degradation.
      Consequently, the turnover of mitochondria progressively declines, resulting in
      decreased ATP synthesis and enhanced formation of reactive oxygen species,
      inducing further mitochondrial damage and additional lipofuscin formation. With
      advancing age, lipofuscin-loaded lysosomes and defective mitochondria occupy
      increasingly larger parts of long-lived postmitotic cells, leaving less and less
      capability for normal turnover and ATP production, finally resulting in cell
      death.

PMID- 16803968
TI  - Methionine sulfoxide reductases: relevance to aging and protection against
      oxidative stress.
AB  - Proteins are subject to modification by reactive oxygen species (ROS), and
      oxidation of specific amino acid residues can impair their biological function,
      leading to an alteration in cellular homeostasis. Methionine is among the amino
      acids the most susceptible to oxidation by almost all forms of ROS, resulting in
      both S and R diasteroisomeric forms of methionine sulfoxide. These modifications
      can be repaired specifically by the peptide methionine sulfoxide reductase A and
      B enzymes (MsrA and MsrB), respectively. MsrA has been detected in several
      organisms going from prokaryotes to eukaryotes. MsrA is tightly implicated in
      protection against oxidative stress and in protein maintenance, which is critical
      in the aging process. Several studies have shown that overexpression of MsrA led
      to an increased resistance against oxidative stress, while MsrA null mutants are
      more sensitive toward oxidative stress. Since oxidative damage is a key factor in
      aging, overexpression of MsrA in some organisms led to an increased life span
      whereas deletion of the gene led to the opposite. MsrA could also be involved, by
      regulating the function and/or expression of target proteins, in ROS-mediated
      signal transduction. In fact, changes in gene expression, including certain
      oxidative stress-response genes, have been observed when MsrA is overexpressed.
      This review elaborates on the current knowledge in the implication of the Msr
      system in protection against oxidative stress and aging.

PMID- 16803969
TI  - Inadequate intensity of various components of total environmental signals can
      lead to natural aging.
AB  - We suppose that natural aging derives from an inevitable shift in certain
      parameters of physiological control systems under the influence of inadequate
      environmental conditions, which are not able to fully induce an organism's
      "optimal" existence in the self-maintenance mode. In this case the rate of aging
      is proportional to the multidimensional difference between the cues from
      evolutionarily designed adequate habitat and signals from the real environment.
      The negative correlation between parameters of Gompertzian mortality (and some
      other published findings) is compatible with this view. Here we discuss examples
      from intracellular to organism level in order to show that adequate patterns of
      outer signals can reverse some aging manifestations.

PMID- 16803970
TI  - Cellular redox regulation and prooxidant signaling systems: a new perspective on
      the free radical theory of aging.
AB  - The overarching role of coenzyme Q(10) in gene regulation, bioenergy formation,
      cellular redox poise regulation, and hydrogen peroxide formation is presented.
      Coenzyme Q(10) has a central role acting as a prooxidant in the generation of
      H(2)O(2). Contrary to the dogma that superoxide and H(2)O(2) formation are highly
      deleterious to cell survival this premise is rejected. Data are discussed that
      continuous superoxide and hydrogen peroxide formation are essential for normal
      cell function and that they play a major role in subcellular redox state
      modulation. It is the prooxidant activity of the so-called antioxidants that may
      be responsible for previously claimed benefits for high doses of oxido-reduction
      nutritional supplements such as alpha lipoic acid and coenzyme Q(10). Oxygen-free
      radical formation is essential for the biological function and is not a direct
      causation of the mammalian aging process; aging is a multisystem stochastic
      process.

PMID- 16803971
TI  - Human immunosenescence: does it have an infectious component?
AB  - The rate of acceleration of the frequency of death due to cardiovascular disease
      or cancer increases with age from middle age up to around 75-80 years, plateauing
      thereafter. Mortality due to infectious disease, however, does not plateau, but
      continues to accelerate indefinitely. The elderly are particularly susceptible to
      novel infectious agents such as SARS, as well as to previously encountered
      pathogens. Why is this? The elderly commonly possess oligoclonal expansions of T
      cells, especially of CD8 cells, which, surprisingly, are associated with
      cytomegalovirus (CMV) seropositivity. This in turn is associated with many of the
      same phenotypic and functional alterations to T cell immunity that have been
      suggested as biomarkers of immune system aging. We suggest that, in fact, CMV,
      not age per se, is the prime driving force behind many or most of the oligoclonal
      expansions and altered phenotypes and functions of CD8 cells in the elderly.
      Thus, the manner in which CMV and the host immune system interact (over which
      period? on which genetic background? with which co-infections?) is critical in
      determining the "age" of adaptive immunity and hence human longevity. In this
      respect, immunosenescence is infectious.

PMID- 16803972
TI  - Aging in mouse and human systems: a comparative study.
AB  - This article discusses the significance of mouse models as a basis for
      elucidating the aging process in humans. We identify certain parallels between
      mouse and human systems and review the theoretical and empirical support for the
      claim that the large divergence in the rate of aging between the two species
      resides in differences in the stability of their metabolic networks. We will show
      that these differences in metabolic stability have their origin in the different
      ecological constraints the species experience during their evolutionary history.
      We exploit these ideas to compare the effect of caloric restriction on murine and
      human systems. The studies predict that the large increases in mean life span and
      maximum life-span potential observed in laboratory rodents subject to caloric
      restriction will not obtain in human populations. We predict that, in view of the
      different metabolic stability of the two systems, caloric restriction will have
      no effect on the maximum life-span potential of humans, and a relatively minor
      effect on the mean life span of nonobese populations. This article thus points to
      certain intrinsic limitations in the use of mouse models in elucidating the aging
      process in humans. We furthermore contend the view that these limitations can be
      mitigated by considering the metabolic stability of the two species.

PMID- 16803973
TI  - Extrapolaholics anonymous: why demographers' rejections of a huge rise in cohort
      life expectancy in this century are overconfident.
AB  - Criticisms of demographers by other demographers have become frequent in
      scientific literature, generally consisting of accusations that trends observed
      in the recent past have been extrapolated unjustifiably into the future.
      Demographers, along with their colleagues in the actuarial profession, are in an
      invidious position in this regard, knowing full well that extrapolation is almost
      always only minimally justifiable, but knowing also that their readers,
      colleagues, and sources of funding tend to be much more interested in the future
      than in the past. It is unfortunate that, while actuaries typically resolve this
      dilemma by emphasizing the limitations of their methods and thereby lowering
      expectations that their predictions will be accurately fulfilled, demographers
      are more prone to respond combatively, attempting to reinforce the credibility of
      their extrapolations by recourse to data from areas in which their expertise is
      less tested, such as biology. This is valuable in that it raises the profile of
      the debate on the likely rate of scientific progress relevant to mortality rates,
      but it also runs the risk of lowering the technical quality of that debate, by
      telling policy makers and the public what they want to hear and thereby
      entrenching their expectations without recourse to the relevant biological facts.
      Extrapolations based on plausible sequences of scientific advances and the
      sociopolitical responses to them, summarized in this article, have led to the
      prediction of four-digit life expectancies of cohorts born in the 21st century
      and possibly even in the 20th. This prediction has attracted inevitable ridicule
      from prominent demographers, but being founded on science and sociology rather
      than on history it may be much more reliable than the extrapolations that those
      demographers presently prefer.

PMID- 16803974
TI  - The value of life and the value of life extension.
AB  - Recent developments in aging research have added new urgency to the bioethical
      debate concerning life and death issues, the value of life, and the reasonable
      limits of medicine. This paper analyzes the basic structures of the liberal and
      conservative components of this debate, showing that there has hitherto been
      inadequate analysis on both sides concerning the nature and implications of the
      value of life, as well as, and as distinct from the value of life extension.
      Classic concepts of the intrinsic or extrinsic value of life are argued to be
      tangential or actually irrelevant to the value of life's continuance and so to
      the value of life extension. An analysis of personhood is proposed which focuses
      explicitly upon the value of life extension to persons. This analysis shows that
      persons may only intelligibly be understood as processes, for whom life extension
      is an inalienable and fundamental value. It is further proposed that, properly
      understood, such an analysis may significantly narrow the liberal/conservative
      divide in bioethics.

PMID- 16803975
TI  - OXPHOS Supercomplexes: respiration and life-span control in the aging model
      Podospora anserina.
AB  - Recent biochemical evidence has indicated the existence of respiratory
      supercomplexes as well as ATP synthase oligomers in the inner mitochondrial
      membrane of different eukaryotes. We have studied the organization of the
      respiratory chain of a wild-type strain and of two long-lived mutants of the
      filamentous fungus Podospora anserina. This aging model is able to respire by
      either the standard or the alternative pathway. In the latter, electrons are
      directly transferred from ubiquinol to the alternative oxidase (AOX) and thus
      bypass complexes III and IV. We showed that the two pathways are composed of
      distinct respiratory supercomplexes. These data are of significance for the
      understanding of both respiratory pathways as well as of life-span control and
      aging.

PMID- 16803976
TI  - Unraveling age-dependent variation of the mitochondrial proteome.
AB  - Blue-native and colorless-native gel electrophoresis combined with subsequent 2D
      SDS-PAGE and MALDI mass spectrometry are successfully applied for understanding
      the role of mitochondria in cellular dysfunction, aging, and cellular death. The
      partial mitochondrial proteome maps of various tissues (liver, brain, kidney,
      heart, and skeletal muscle) obtained from rat serve now as a database for the
      elucidation of age-dependent changes, including alterations in protein-protein
      interactions as well as in posttranslational modifications.

PMID- 16803977
TI  - Using Caenorhabditis elegans as a model for aging and age-related diseases.
AB  - During the last three decades the soil nematode C. elegans has become a prominent
      model organism for studying aging. Initially research in the C. elegans aging
      field was focused on the genetics of aging and single gene mutations that
      dramatically increased the life span of the worm. Undoubtedly, the existence of
      such mutations is one of the main reasons for the popularity of the worm as model
      system for studying aging. However, today many different approaches are being
      used in the C. elegans aging field in addition to genetic manipulations that
      influence life span. For example, environmental manipulations such as caloric
      restriction and hormetic treatments, evolutionary studies, population studies,
      models of age-related diseases, and drug screening for compounds that extend life
      span are now being investigated using this nematode. This review will focus on
      the most recent developments in C. elegans aging research with the aim of
      illustrating the diversity of the field.

PMID- 16803978
TI  - Age-dependent decrease in renal glucocorticoid receptor function is reversed by
      dietary restriction in mice.
AB  - The effects of age and dietary restriction (alternate days of feeding for 3
      months) on the concentration, activation, and DNase I digestion of nuclear-bound
      glucocorticoid receptors (GRs) in the kidney of male mice at two different ages
      (5 months as adult and 20 months as old) were investigated. A significant
      decrease (30%) in the concentration of renal GRs was observed in older ad libitum
      (AL)-fed mice as compared to the adult mice. Dietary restriction (DR) of older
      mice significantly increased (28%) the level of GRs as compared to the AL-fed
      control animals. The affinity of the receptor for the hormone remained the same
      for both AL- and DR-fed animals at both ages. Scatchard and slot blot analyses of
      the data confirmed the decreased level of renal GRs in older mice compared to the
      adult mice as well as an increased level of receptor in older DR mice. Activation
      studies of GRs by both salt and heat indicated a decreased (15-20%) activation of
      renal GRs in older animals compared to the adult mice in the AL-fed group. It was
      further observed that DR significantly enhanced (30%) the degree of both salt-
      and heat-dependent activation of GRs in older animals compared to the AL-fed
      animals of the age-matched group. DNase I digestion and extraction of nuclear
      bound GR complexes showed a lower degree (26%) of extraction in older AL-fed
      animals compared to the adult animals. However, DR did not alter the pattern of
      digestibility of bound GR complexes. These above findings indicate that DR could
      reverse the decrease of GR function in older animals and may provide better
      adaptability of kidney in water and electrolyte balance.

PMID- 16803979
TI  - Investigation of differentially expressed genes in the ventricular myocardium of
      senescent rats.
AB  - Aging alters a variety of physiological functions of the heart. The molecular
      basis of the age-related functional changes has not been fully understood.
      Differential gene expression provides the basis for many fundamental cellular
      processes associated with development and aging. The identification and cloning
      of genes whose expression is modulated by aging can be of importance for our
      better understanding of these age-related phenomena. In order to isolate and
      characterize gene products differentially expressed in senescent hearts, we
      applied a differential display method for screening those genes in rat
      ventricular myocardium. Total RNAs were isolated from 2-month-old (young) and 24
      month-old rat (senescent) ventricles by the acid-guanidium-phenol-chloroform
      method. The first-strand synthesis of the cDNAs from each RNA was carried out
      with oligo-d(T) primers. The differential display screening was performed with
      three arbitrary primers and eight anchor primers, and the products were isolated
      on a 6% denaturing polyacrylamide gel. The bands showing differential expression
      were excised and subcloned into T-vector. We selected 19 upregulated clones and
      66 downregulated clones in aged rat hearts. The differential expression of those
      candidate genes was confirmed by reverse Northern blot analysis. The selected
      genes were sequenced by dye-terminator methods. Among 31 clones, 15 clones were
      unknown. The known products included alpha-myosin heavy chain, cytochrome oxidase
      subunit, H(+)-transporting ATP synthase F0 complex subunit c isoform 3 (ATP5G3),
      and Na(+)-K(+)-Cl(-) cotransporter. The RT-PCR differential display method
      effectively identified genes differentially expressed in senescent hearts, and
      may be a useful tool for investigating factors responsible for age-related
      physiological changes.

PMID- 16803980
TI  - Naive T cells in the elderly: are they still there?
AB  - One of the most striking changes in the primary lymphoid organs during human
      aging is the progressive involution of the thymus. As a consequence, the rate of
      naive T cell output dramatically declines with age and the peripheral T cell pool
      shrinks. These changes lead to increased incidence of severe infections and
      decreased protective effect of vaccinations in the elderly. Little is, however,
      known of the composition and function of the residual naive T cell repertoire in
      elderly persons. To evaluate the impact of aging on the naive T cell pool, we
      investigated the quantity, phenotype, function, composition, and senescence
      status of CD45RA(+)CD28(+) human T cells--a phenotype generally considered as
      naive cells--from both young and old healthy donors. We found a significant
      decrease in the number of CD45RA(+)CD28(+) T cells in the elderly, whereas the
      proliferative response of these cells is still unimpaired. In addition to their
      reduced number, CD45RA(+)CD28(+) T cells from old donors display significantly
      shorter telomeres and have a restricted TCR repertoire in nearly all 24 Vbeta
      families. These findings let us conclude that naive T cells cannot be classified
      with conventional markers in old age.

PMID- 16803981
TI  - Brain lipopigment accumulation in normal and pathological aging.
AB  - A principal marker of brain vulnerability, stress, aging, and related pathology
      is represented by lipopigments (LPs)--lipofuscin, and ceroid. During ontogenesis,
      neuronal LP accumulations are significantly correlated with important changes in
      nerve cell morphology and biochemistry. In the aged neurons, LPs are present in
      all cellular compartments. Moreover, neuronal LP accumulations coexist with glial
      LP storage, especially in microglia. Owing to their transporting properties, and
      the migration capacity of microglia, glial cells deposit LP clusters in
      pericapillary areas. Thus, LP conglomerates appear in the whole nervous tissue,
      creating specific patterns of LP architectonics. Direct interrelations, critical
      LP concentrations, which generate cascades of negative subcellular events, and
      indirect impairment correlations determine characteristic neuropathologic aging
      profiles. These specific and associated negative neuropathologic consequences of
      LP accumulation have multiple and detrimental impacts on neuron and glia
      homeostasis, ranging from neuronal function to central nervous system physiology.

PMID- 16803982
TI  - Aging and orchidectomy modulate expression of VEGF receptors (Flt-1 and Flk-1) on
      corpus cavernosum of the rat.
AB  - Aging and hypogonadic states are known risk factors for erectile dysfunction
      (ED), contributing together to vascular damage of penile tissue. In the present
      study, VEGF-specific membrane receptor (VEGFR-1/Flt-1 and VEGFR-2/Flk-1)
      expression was studied by confocal immunofluorescence in the corpus cavernosum of
      control rats, rats aged 12 and 18 months, and orchidectomized Wistar rats (90
      days of bilateral orchidectomy). Immunocytochemical results demonstrated VEGFR-2
      expression restricted to the endothelium in both control and orchidectomized
      rats. Aged animals (12 and 18 months) presented enlarged vessels with intense
      VEGFR-2 endothelial staining. On the other hand, VEGFR-1 was demonstrated in
      smooth muscle fibers, particularly in those that surround vessel endothelium, the
      endothelial expression being very low in control and orchidectomized rats.
      However, in the aged rats, a shift resulting in a VEGFR-1 and VEGFR-2 co
      localization in the endothelial cell was observed. The findings suggest an
      upregulation of VEGFR-1 in the corpora cavernosa during aging in the rat, which
      is evident from an increased expression by endothelial cells.

PMID- 16803985
TI  - DNA damage by free radical production by aminoguanidine.
AB  - Aminoguanidine (AG), a prototype therapeutic dicarbonyl scavenger, is the most
      potent drug available today to inhibit the formation of advanced glycation
      endproducts (AGEs) and to reverse glycation-mediated damage in normal aging. This
      paper examines the ability of AG to cause damage to supercoiled plasmid DNA in
      the presence of the transition metal, Fe(+3). Damage to DNA was dependent on the
      concentrations of both the transition metal and AG. We could detect hydroxyl
      radical as well as hydrogen peroxide during the incubation of AG with Fe(+3).
      Thus this finding further cautions against the indiscriminate use of AG in
      clinical prophylaxis in diabetes and questions its use as a therapeutic agent.

PMID- 16803984
TI  - Mitochondria damage checkpoint, aging, and cancer.
AB  - There is growing evidence supporting the progressing decline in mitochondrial
      function with age. Mitochondria are the major site of reactive oxygen species
      (ROS) production in the cell; therefore it is likely that progressive decline in
      mitochondrial function is due to the accumulation of oxidative damage with age.
      Despite this notion, a role for mitochondria in cellular senescence has been
      largely ignored. Our studies using mitochondrial gene knockout cells (rho(0))
      from a variety of tissue types demonstrate that loss of mitochondrial function
      leads to cell cycle arrest, cellular senescence, and tumorigenic phenotype. In
      light of these and earlier studies we hypothesize the existence of a mitochondria
      damage checkpoint (mitocheckpoint) in human cells. Mitocheckpoint permits cells
      to arrest in the cell cycle in order to repair/restore mitochondrial function to
      the normal level. Upon overwhelming, persistent, or severe damage to
      mitochondria, mitocheckpoint machinery may allow cells to undergo senescence.
      Thus cellular senescence may function as another checkpoint before cells decide
      to initiate programmed cell death resulting in aging of tissues and organs.
      Alternatively, mutations occur in the mitochondrial and/or nuclear DNA, resulting
      in tumorigenesis.

PMID- 16803983
TI  - Role of angiotensin II and endothelin-1 receptors in aging-related functional
      changes in rat cardiovascular system.
AB  - Angiotensin II (AII) and endothelin-1 (ET-1) are regarded as key players in the
      age-related changes in cardiovascular function. They are known to be involved in
      the pathogenesis of cardiac fibrosis and coronary vascular atherosclerosis. AII-
      and ET-induced vasoconstriction was augmented in coronary arteries of Langendorff
      perfused heart from aged rats. In papillary muscles, ET-1-induced positive
      inotropic effect (PIE) was diminished by aging. On the other hand, both ET-1 and
      AII caused greater vasoconstriction in aged rat coronary arteries compared to
      those in the young rat. To further elucidate the mechanism of these age-dependent
      changes in cardiovascular effects of ET-1 and AII, we examined the expression of
      AII and ET-1 receptors in young (2-month-old) and aged (24-month-old) rats. Total
      RNA was isolated from left ventricles. For determination of the gene expression
      of AT(1) receptor and ET(A)/ET(B) receptor mRNA, competitive RT-PCR and Northern
      blot analysis were performed, respectively. [(125)I]ET-1 receptor assay was
      carried out in left ventricular membrane fraction. AT(1)-receptor, ET(A)-, and
      ET(B)-receptor mRNA were upregulated in the left ventricles of senescent rats
      compared with young ones. The affinity of ET-1-receptor was not changed, but
      receptor density was significantly increased in aged rats. Although the precise
      mechanism for the upregulation of AT(1) receptor and ET-1 receptor in the aged
      rat heart has not been clarified yet, these findings suggest that the activation
      of the renin-angiotensin system as well as ET receptor may be important for the
      physiological changes in aged hearts.

PMID- 16803986
TI  - Effect of lipid restriction on mitochondrial free radical production and
      oxidative DNA damage.
AB  - Many studies have shown that caloric restriction (40%) decreases mitochondrial
      reactive oxygen species (ROS) generation in rodents. Moreover, we have recently
      found that 7 weeks of 40% protein restriction without strong caloric restriction
      also decreases ROS production in rat liver. This is interesting since it has been
      reported that protein restriction can also extend longevity in rodents. In the
      present study we have investigated the possible role of dietary lipids in the
      effects of caloric restriction on mitochondrial oxidative stress. Using
      semipurified diets, the ingestion of lipids in male Wistar rats was decreased by
      40% below controls, while the other dietary components were ingested at exactly
      the same level as in animals fed ad libitum. After 7 weeks of treatment the liver
      mitochondria of lipid-restricted animals showed significant increases in oxygen
      consumption with complex I-linked substrates (pyruvate/malate and
      glutamate/malate). Neither mitochondrial H(2)O(2) production nor oxidative damage
      to mitochondrial or nuclear DNA was modified in lipid-restricted animals.
      Oxidative damage to mitochondrial DNA was one order of magnitude higher than that
      of nuclear DNA in both dietary groups. These results deny a role for lipids and
      reinforce the possible role of dietary proteins as being responsible for the
      decrease in mitochondrial ROS production and DNA damage in caloric restriction.

PMID- 16803987
TI  - Establishment of H2O2-induced premature senescence in human fibroblasts
      concomitant with increased cellular production of H2O2.
AB  - Premature senescence of human fibroblasts is established after exposure to an
      acute sublethal concentration of H(2)O(2). Overexpression of transforming growth
      factor-beta1 (TGF-beta1) was shown to be responsible for the appearance of the
      biomarkers of senescence in these conditions. Other studies have shown that
      incubation of human fibroblasts with TGF-beta1 leads to overexpression of
      H(2)O(2). In this work, we show an increased production of H(2)O(2) by human
      fibroblasts as premature senescence is established after an initial exposure to
      H(2)O(2).

PMID- 16803988
TI  - CARF regulates p19ARF-p53-p21WAF1 senescence pathway by multiple checkpoints.
AB  - CARF was first cloned as a novel binding partner of ARF from a yeast-interactive
      screen. CARF and ARF colocalize in the perinucleolar region and have a
      collaborative function. In the nucleoplasm, CARF interacts with p53 and enhances
      its function. We demonstrate that p53 downregulates CARF in a negative feedback
      regulatory loop and may also involve p53 antagonist HDM2.

PMID- 16803989
TI  - Structural and functional differences between mouse mot-1 and mot-2 proteins that
      differ in two amino acids.
AB  - Chaperone functions mediated by the heat-shock protein (HSP) family constitute a
      fundamental mechanism that governs the life span of organisms. Here we
      investigated the chaperone activities of the mitochondrial HSP70 protein,
      mortalin, which is a heat-uninducible stress protein involved in immortalization
      and tumorigenesis. There are two mortalin alleles, mot-1 and mot-2, in mouse,
      encoding two distinct proteins. Whereas an overexpression of mot-1-induced
      senescence in NIH 3T3 cells, overexpression of mot-2 promoted their malignant
      properties. Here, we provide evidence that mot-1 possesses very low chaperone
      activity as compared to mot-2. A "lazy lid" hypothesis is proposed for their
      differential aging phenotypes.

PMID- 16803990
TI  - Proteasomal oscillation during mild heat shock in aging human skin fibroblasts.
AB  - Augmentation of proteasome machinery is emerging as a significant
      gerontomodulatory consequence of hormetic stimulation, such as mild heat stress.
      This study describes the phenomenon we term hormetic proteasomal oscillation,
      wherein mildly heat-stressed human fibroblasts (41 degrees C, 1 h) display an
      adaptation response pattern in proteasome activity. Remarkably, such response
      appears to be diverse in severely heat-stressed or senescent fibroblasts. This
      proteasomal oscillation, as an innate cellular reaction to heat and aging,
      however, is independent of 20S proteasome protein levels and nuclear factor-E2
      related factor 2 (Nrf2) transactivation.

PMID- 16803991
TI  - Apoptosis and necrosis in senescent human fibroblasts.
AB  - To study the role of cell death in the aging process, cell death during
      spontaneous cellular senescence in vitro was examined with normal human
      fibroblasts. A small subset of the senescent cells showed aberrant morphology
      such as remarkable nuclear fragmentation or multiple micronuclei, and such cells
      often showed positive reactions with antibody to phosphorylated pRb. Cells
      showing caspase activation and binding of Annexin V, which indicate apoptotic
      change, increased in the senescent phase in flow cytometry analysis. Propidium
      iodide-positive cells, however, also increased with passaging. The results
      suggest that both apoptosis and necrosis are involved in cell death of senescent
      human fibroblasts.

PMID- 16803992
TI  - Aging of murine mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are able to differentiate into distinct lineages
      such as adipo-, osteo-, and chondrocytes. MSCs were isolated from three mouse
      strains, which are short- (SAMP6, 9.7 months), medium- (SAMR1, 16.3 months), or
      long-lived (C57BL/6, 28 months). We investigated primary colony-forming units
      with regard to bone marrow stroma and found differences that correlate with mean
      life expectancies of the particular genetic backgrounds. However, MSC derived
      from the various mouse strains behaved equivalently in vitro with respect to
      growth rate. By genomic means, we analyzed the cellular milieu in vivo and found
      considerable differences among the various mouse strains. This implies that,
      although individual MSCs show an equivalent differentiation potential in vitro,
      the primary stem cells are greatly influenced by their molecular environment.

PMID- 16803993
TI  - Prevention of accelerated cell aging in the Werner syndrome.
AB  - In the Werner syndrome (WS) fibroblasts have an increased life span and growth
      rate when treated with the p38 inhibitor SB203580. Additionally, the cellular
      morphology reverts to that seen in young normal fibroblasts. The p38 pathway is
      activated in young WS cells, associated with high levels of p21(WAF1) leading to
      cell cycle arrest, and is suppressed by SB203580. As these changes are also seen
      in telomerized WS cells, these data show that the growth problems seen in WS
      cells, and perhaps the accelerated in vivo aging, are due to a telomere
      independent premature senescence mechanism. The suppression of this mechanism by
      SB203580 treatment suggests a route whereby WS may be amenable to therapeutic
      intervention.

PMID- 16803994
TI  - Oxidative stress induces intralysosomal accumulation of Alzheimer amyloid beta
      protein in cultured neuroblastoma cells.
AB  - Oxidative stress is considered important for the pathogenesis of Alzheimer's
      disease (AD), which is characterized by the formation of extracellular senile
      plaques, mainly composed of amyloid beta-protein (Abeta). Abeta also accumulates
      within AD neurons and is believed to exert cellular toxicity through lysosomal
      labilization. We report that the exposure of human neuroblastoma cells to
      hyperoxia (40% vs. 8% ambient oxygen) induced the accumulation of large (over 1
      microM) Abeta-containing lysosomes, which were not typical of control cells,
      showing a distinct localization of Abeta and lysosomal markers. An inhibitor of
      autophagy, 3-methyladenine, suppressed the effect of hyperoxia. The results
      suggest a link between the involvement of oxidative stress and lysosomes in AD.

PMID- 16803995
TI  - The genetics of human longevity.
AB  - Aging is due to a complex interaction of genetic, epigenetic, and environmental
      factors, but a strong genetic component appears to have an impact on survival to
      extreme ages. In order to identify "longevity genes" in humans, different
      strategies are now available. In our laboratory, we performed association studies
      on a variety of "candidate" polymorphisms in Italian centenarians. Many
      genes/polymorphisms gave negative results, while others showed a positive
      association with human longevity and a sometimes-positive association with
      unsuccessful aging (myocardial infarction, Alzheimer's disease, and type 2
      diabetes). Results regarding genes involved in inflammation (IL-1 cluster, IL-6,
      IL-10, TNF-alpha, TGF-beta, TLR-4, PPARgamma), insulin/IGF-1 signaling pathway
      and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53,
      p66(shc)) will be described. In addition, a strong role of the interaction
      between nuclear and mitochondrial genomes (mtDNA haplogroups and the C150T
      mutation) emerged from our findings. Thus, the genetics of human longevity
      appears to be quite peculiar in a context where antagonistic pleiotropy can play
      a major role and genes can have a different biological role at different ages.

PMID- 16803996
TI  - Search for genetic factors associated with susceptibility to multiple sclerosis.
AB  - Multiple sclerosis (MS) is a cell-mediated autoimmune disease characterized by
      type-1 cytokine production. Environmental and individual genetic background might
      influence this response particularly in cytokine gene polymorphisms. We evaluated
      whether polymorphisms of interleukin (IL)-10, IL-12, and tumor necrosis factor
      (TNF)-alpha genes, which might play a role in MS pathogenesis, are associated
      with MS susceptibility. Genotype frequencies for all the analyzed polymorphisms
      were not differently distributed between cases and controls. It is reasonable to
      suppose that the cytokine single-nucleotide polymorphisms (SNPs) studied must be
      considered against a larger genetic background involving other functional SNPs of
      Th1 regulator elements such as IL-21 and IL-23.

PMID- 16803997
TI  - Opposite role of pro-inflammatory alleles in acute myocardial infarction and
      longevity: results of studies performed in a Sicilian population.
AB  - The major trait characterizing offspring in centenarians is a reduction in the
      prevalence of cardiovascular disease. Because a pro-inflammatory genotype seems
      to contribute significantly to the risk of coronary heart disease, alleles
      associated with disease susceptibility would not be included in the genetic
      background favoring longevity, as suggested by our previous studies on
      inflammatory cytokines. To confirm whether genotypes of inflammatory molecules
      play an opposite role in atherosclerosis and longevity, we are studying the role
      of other proinflammatory alleles, such as pyrin and CCR5, in acute myocardial
      infarction and longevity. The results support the hypothesis that the genetic
      background favoring cardiovascular diseases is detrimental to longevity. In
      addition, they suggest that the centenarian genetic background may be useful for
      investigating genetic key components of age-associated diseases that are
      characterized by a multifactorial etiology.

PMID- 16803998
TI  - Association between +1059G/C CRP polymorphism and acute myocardial infarction in
      a cohort of patients from Sicily: a pilot study.
AB  - Inflammation plays a role in all the phases of atherosclerosis, and increased
      production of the acute-phase reactant, C-reactive protein (CRP), predicts future
      cardiovascular events. Furthermore, CRP has been claimed to play a role in the
      pathogenesis of atherosclerosis; therefore, CRP polymorphisms might be associated
      with acute myocardial infarction (AMI). We have analyzed male patients affected
      by AMI and healthy age-related male controls from Sicily for +1059G/C CRP single
      nucleotide polymorphism (SNP). There was a significantly higher frequency of
      +1059C SNP (P = 0.0008; OR 3.86) in patients compared to controls. CRP serum
      levels were significantly higher in C+ healthy subjects rather than in C-
      subjects (P = 0.0075). The results of the present pilot case-control study
      performed in a homogeneous caucasoid population suggest that +1059C CRP gene SNP
      is associated with AMI. In any case, the results of the present study should add
      to the growing body of evidence on the role of pro-inflammatory genotypes in
      unsuccessful aging, determining susceptibility to immune-inflammatory diseases
      such as coronary heart disease.

PMID- 16803999
TI  - Inflammation, longevity, and cardiovascular diseases: role of polymorphisms of
      TLR4.
AB  - The total burden of infection at various sites may affect the progression of
      atherosclerosis, the risk being modulated by host genotype. The role of
      lipopolysaccaride receptor TLR4 is paradigmatic. It initiates the innate immune
      response against gram-negative bacteria; and TLR4 polymorphisms, as ASP299GLY,
      suggested to attenuate receptor signaling, have been described. We demonstrated
      that TLR4 ASP299GLY polymorphism shows a significantly lower frequency in
      patients affected by myocardial infarction compared to controls, whereas
      centenarians show a higher frequency. Thus, people genetically predisposed to
      developing weak inflammatory activity, seem to have fewer chances of developing
      cardiovascular diseases (CVD) and, subsequently, live longer if they do not
      become affected by serious infectious diseases. These results are in agreement
      with our other data demonstrating how genetic background may exert the opposite
      effect with respect to inflammatory components in CVD and longevity. In the
      present report, to validate this hypothesis, the levels of interleukin (IL)-6, a
      pro-inflammatory cytokine involved in atherosclerosis and longevity, were
      determined by an enzyme-linked immuno-sorbent assay (ELISA) in supernatants from
      a whole blood assay after stimulation with subliminal doses of lipopolysaccaride
      (LPS) from Escherichia coli (E. coli). The samples, genotyped for the ASP299GLY
      polymorphism, were challenged with LPS for 4, 24, and 48 h. What we found was
      that Il-6 values were significantly lower in carriers bearing TLR4 mutation.
      Therefore, the pathogen burden, by interacting with host genotype, determines the
      type and intensity of the immune-inflammatory responses accountable for pro
      inflammatory status, CVD, and unsuccessful aging. On the other hand, our present
      data seem to explain the inconclusive results obtained in case-control studies
      taking into account the role of functional IL-6 polymorphisms in successful and
      unsuccessful aging. In fact, IL6 levels seem to depend, in addition, on IL-6
      polymorphisms and on innate immunity gene polymorphisms as well.

PMID- 16804000
TI  - Frequency of polymorphisms of signal peptide of TGF-beta1 and -1082G/A SNP at the
      promoter region of Il-10 gene in patients with carotid stenosis.
AB  - The role of inflammation in atherosclerosis is well recognized. We have evaluated
      the allele frequencies of the +869T/C and +915G/C polymorphisms (SNPs) at the TGF
      beta1 gene and -1082G/A SNP at IL-10 promoter sequence, two well-known
      immunosuppressive and anti-inflammatory cytokines, in patients with carotid
      stenosis. Our data suggest a lack of association between these SNPs and the
      susceptibility to atherosclerosis although other reports have demonstrated this
      association. These results may be due to the pleiotropic effects of the cytokines
      and/or differences in haplotype combination that should be investigated to
      elucidate the role of TGF-beta1 and IL-10 polymorphisms in atherosclerosis.

PMID- 16804001
TI  - Reduced expression levels of the senescence biomarker clusterin/apolipoprotein j
      in lymphocytes from healthy centenarians.
AB  - Clusterin/apolipoprotein J (CLU) is a conserved, ubiquitously expressed secreted
      glycoprotein that has been implicated in several physiological processes and was
      found to accumulate in many severe physiological disturbances. We have previously
      shown that the CLU gene and protein are upregulated during replicative
      senescence, stress-induced premature senescence, in vivo aging, and in several
      age-related diseases. In this study we have examined the CLU gene relationship to
      human longevity. We recruited and further analyzed 96 blood samples from Italian
      and Greek healthy donors of different ages, including 49 centenarians. We found
      that although the CLU gene expression levels increase during aging, in the
      centenarians' samples CLU levels were lower than those found in old donors. We
      then investigated the possible existence of a genetic polymorphism related to
      longevity at the CLU structural locus. A neutral noncoding sequence variant was
      detected 35 nucleotides upstream from exon 6, which does not correlate, however,
      with the age of the donor. We conclude that CLU gene accumulation during in vivo
      aging does not directly relate to chronological age, but rather indicates
      increased levels of organismal stress due to a progressive failure of homeostasis
      and/or to prolonged exposure to a stressful environment.

PMID- 16804002
TI  - Heat-shock protein 70 genes and human longevity: a view from Denmark.
AB  - We have studied the association of three single nucleotide polymorphisms (SNPs)
      present in the three HSP70 (heat-shock protein) genes on 6p21 with human
      longevity. The availability of biological samples from various population cohorts
      in Denmark has given us the opportunity to try novel methods of gene association
      with human longevity. A significant association of one haplotype with male
      longevity was observed. Furthermore, a significant difference in the survival of
      the carriers of the different genotypes in females was observed. We also found an
      age-dependant decline in the ability of peripheral blood mononuclear cells to
      respond to heat stress in terms of Hsp70 induction.

PMID- 16804003
TI  - Possible associations between successful aging and polymorphic markers in the
      Werner gene region.
AB  - Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome
      caused by mutations in the Werner (WRN) gene leading to the early onset of many
      (but not all) aspects of normal aging. To investigate whether the WRN gene
      affects the course of aging in non-Werner syndrome individuals, we performed
      association studies analyzing several single nucleotide polymorphisms (SNPs) in
      the WRN locus. We found certain close-set SNPs in the 5' flanking region and 5'
      UTR to be significantly associated with the cognitive functioning level in old
      age.

PMID- 16804004
TI  - The pattern of chromosome-specific variations in telomere length in humans shows
      signs of heritability and is maintained through life.
AB  - This paper characterizes the distribution of telomere length on individual
      chromosome arms in humans. By fluorescent in situ hybridization (FISH), followed
      by computer-assisted analysis of digital images, it is shown that the
      distribution of telomere length on individual chromosome arms is not random, but
      that humans have a common telomere profile. This profile exists in lymphocytes,
      amniocytes and fibroblasts, and seems to be conserved during life. A closer look
      at the overall pattern of the profile shows that the length of the telomeres in
      general follows the total chromosome length. In addition to the common profile,
      it is found that each person has specific characteristics, which are also
      conserved throughout life. Studying both twins and families we have obtained
      indications that these individual characteristics are at least partly inherited.
      Altogether, our results suggest that the length of individual telomeres might
      occasionally play a role in the heritability of life span.

PMID- 16804005
TI  - Identification of genes involved in healthy aging and longevity.
AB  - Studies suggest that the region around microsatellite marker D4S1564 on
      chromosome 4 is in some way linked to longevity. As a part of the integrated
      European project Genetics of Healthy Aging (GeHA), we set out to investigate the
      genes found in this region using a proteomics approach. Here, we report the
      cloning of six candidate genes.

PMID- 16804006
TI  - Prevention and treatment of skin aging.
AB  - Skin aging is a complex biological process that is a consequence of both
      intrinsic or genetically programmed aging that occurs with time, and extrinsic
      aging caused by environmental factors. The dramatic increase in the aging
      population and the psychosocial impact of skin aging has created a demand for
      effective interventions. The advances that have been made in the past 25 years in
      our understanding of the clinical, biochemical, and molecular changes associated
      with aging have led to the development of many different approaches to reduce,
      postpone, and in some cases, repair the untoward effects of intrinsic programmed
      aging and extrinsic environmental injury.

PMID- 16804007
TI  - Kinetin-induced differentiation of normal human keratinocytes undergoing aging in
      vitro.
AB  - Kinetin (N(6)-furfuryladenine) is a cytokinin growth factor having several anti
      aging effects reported for human cells and fruit flies. We have observed that
      short-term culturing of human keratinocytes in the presence of 40 to 200 microM
      kinetin results in a significant inhibition of cell growth. Studies were
      undertaken to analyze the process of differentiation as a reason for growth
      inhibition. Keratinocytes at different passage levels were treated with fetal
      calf serum (FCS) and calcium as differentiation-inducing positive controls, with
      different concentrations of kinetin, and with a combination of kinetin and
      calcium. The induction and progression of differentiation was monitored by
      morphological observations and by using several differentiation markers,
      including keratins (K10 and K14), involucrin, epidermal transglutaminase, and
      some new keratinocyte-specific antibodies isolated by the phage display method.
      In young keratinocytes, two days of calcium treatment reduced the K14 level by
      78%, and increased the levels of K10 and involucrin by 40% and 29%, respectively.
      In comparison, 40 microM kinetin had no effect on the K14 level, but increased
      the K10 level by 28% and that of involucrin by four-fold. The combination of
      calcium and 40 microM kinetin led to a decrease by 23% in the K14 level, to an
      increase in the level of K10 by 55%, and to a two-fold rise in the involucrin
      level. These results suggest that the rate, extent, and quality of
      differentiation depend on the inducing agent, and that kinetin may be useful in
      promoting the differentiation of human keratinocytes, especially in the presence
      of calcium.

PMID- 16804010
TI  - The roles of satellite cells and hematopoietic stem cells in impaired
      regeneration of skeletal muscle in old rats.
AB  - Sarcopenia is the involuntary loss of skeletal muscle mass and strength that
      occurs with aging, resulting in physical frailty. One potential explanation for
      sarcopenia is the failure of muscle to regenerate after damage, some of which may
      be due to changes in the function of satellite cells. Recent studies have
      identified novel populations of adult stem cells in skeletal muscle, such as
      hematopoietic stem cells. To understand the cellular mechanisms of sarcopenia, we
      examined the expression of satellite cells and hematopoietic stem cells in old
      regenerating muscles based on the expression profiles of several markers related
      to those cells.

PMID- 16804008
TI  - Epidermal and dermal characteristics in skin equivalent after systemic and
      topical application of skin care ingredients.
AB  - Effects of active ingredients from topical and systemic skincare products on
      structure and organization of epidermis, dermal-epidermal junction (DEJ), and
      dermis were examined using an in vitro reconstructed skin equivalent (SE).
      Imedeen Time Perfection (ITP) ingredients (a mixture of BioMarine Complex, grape
      seed extract, tomato extract, vitamin C) were supplemented systemically into
      culture medium. Kinetin, an active ingredient from Imedeen Expression Line
      Control Serum, was applied topically. Both treatments were tested separately or
      combined. In epidermis, all treatments stimulated keratinocyte proliferation,
      showing a significant increase of Ki67-positive keratinocytes (P < 0.05). Kinetin
      showed a twofold increase of Ki67-positive cells, ITP resulted in a fivefold, and
      ITP+kinetin showed a nine-fold increase. Differentiation of keratinocytes was
      influenced only by kinetin since filaggrin was found only in kinetin and
      kinetin+ITP samples. At the DEJ, laminin 5 was slightly increased by all
      treatments. In dermis, only ITP increased the amount of collagen type I. Both
      kinetin and ITP stimulated formation of fibrillin-1 and elastin deposition. The
      effect of kinetin was seen in upper dermis. It stimulated not only the amount of
      deposited fibrillin-1 and elastin fibers but also their organization
      perpendicularly to the DEJ. ITP stimulated formation of fibrillin-1 in deeper
      dermis. In summary, the combination of topical treatment with kinetin and
      systemic treatment with ITP had complementary beneficial effects in the formation
      and development of epidermis and dermis.

PMID- 16804009
TI  - MAP kinases and heat shock-induced hormesis in human fibroblasts during serial
      passaging in vitro.
AB  - Adult human skin fibroblasts were exposed repeatedly to 41 degrees C or 42
      degrees C heat shock (HS) for 1 h twice a week during serial passaging throughout
      their replicative life span. On the basis of longevity curves, cell size, and
      morphology, we observed that repeated mild heat shock (RMHS) at 41, degrees C had
      strong anti-aging hormetic effects, including 20% extension of cellular
      longevity. The basal levels of the MAP kinases JNK1, JNK2, and p38 increased
      during serial passaging, while that of ERK2 decreased. RMHS further exaggerated
      these effects, which suggests that age-related changes in MAP kinases may be an
      adaptive response for better cell survival.

PMID- 16804011
TI  - Age-related effects of dexamethasone administration in adrenal zona reticularis.
AB  - Suppression of adrenocorticotropic hormone results in reduced adrenal steroid
      output, adrenocortical cell atrophy, and apoptosis in young rats. To verify such
      effects during aging, dexamethasone was injected into rats for 3 days at five
      different ages; at day 4, adrenals and blood were collected for morphologic and
      corticosterone assay. Adrenal structure was similar at all ages, but in
      dexamethasone-injected animals there were ultrastructural features of apoptosis
      and a higher percentage of TUNEL and caspase-3-labeled nuclei and cytoplasm;
      their corticosterone decreased significantly. In both groups, there was age
      related decrease in the percentage of apoptotic cells, significant only in
      dexamethasone-injected rats. The data suggest that aged adrenocortical cells are
      less susceptible to the lack of adrenocorticotropic hormone (ACTH), possibly as a
      result of their decreased functional ability.

PMID- 16804012
TI  - Does chronic glycolysis accelerate aging? Could this explain how dietary
      restriction works?
AB  - The mechanisms by which dietary restriction (DR) suppresses aging are not
      understood. Suppression of glycolysis by DR could contribute to controlling
      senescence. Many glycolytic intermediates can glycate proteins and other
      macromolecules. Methyglyoxal (MG), formed from dihydroxyacetone- and
      glyceraldehyde-3-phosphates, rapidly glycates proteins, damages mitochondria, and
      induces a prooxidant state to create a senescent-like condition. Ad libitum-fed
      and DR animals differ in mitochondrial activity and glycolytic flux rates.
      Persistent glycolysis in the unrestricted condition would increase the
      intracellular load of glycating agents (e.g., MG) and increase ROS generation by
      inactive mitochondria. Occasional glycolysis during DR would decrease MG and
      reactive oxygen species (ROS) production and could be hormetic, inducing
      synthesis of glyoxalase-1 and anti-glycating agents (carnosine and polyamines).

PMID- 16804013
TI  - Would carnosine or a carnivorous diet help suppress aging and associated
      pathologies?
AB  - Carnosine (beta-alanyl-L-histidine) is found exclusively in animal tissues.
      Carnosine has the potential to suppress many of the biochemical changes (e.g.,
      protein oxidation, glycation, AGE formation, and cross-linking) that accompany
      aging and associated pathologies. Glycation, generation of advanced glycosylation
      end-products (AGEs), and formation of protein carbonyl groups play important
      roles in aging, diabetes, its secondary complications, and neurodegenerative
      conditions. Due to carnosine's antiglycating activity, reactivity toward
      deleterious carbonyls, zinc- and copper-chelating activity and low toxicity,
      carnosine and related structures could be effective against age-related protein
      carbonyl stress. It is suggested that carnivorous diets could be beneficial
      because of their carnosine content, as the dipeptide has been shown to suppress
      some diabetic complications in mice. It is also suggested that carnosine's
      therapeutic potential should be explored with respect to neurodegeneration.
      Olfactory tissue is normally enriched in carnosine, but olfactory dysfunction is
      frequently associated with neurodegeneration. Olfactory administration of
      carnosine could provide a direct route to compromised tissue, avoiding serum
      carnosinases.

PMID- 16804014
TI  - The necessity of having a proper dose of (-)deprenyl (D) to prolong the life
      spans of rats explains discrepancies among different studies in the past.
AB  - (-)Deprenyl (D) has been shown to be effective in prolonging life span in
      experimental animals, although, there are some discrepancies in its effect on the
      life span the even within the same species (rats). The present study aims to
      clarify the reason for these discrepancies. Male F344/DuCrj rats began receiving
      subcutaneous (s.c.) injections of D at the age of 18 months. Doses used were
      0.25, 0.50, and 1.0 mg/kg/injection (inj.), three times a week. Average life
      spans of animals were significantly longer in male rats given 0.25 and 0.5
      mg/kg/inj.; however, rats given a 1.0 mg/kg dose began dying earlier than control
      rats, leading to an inverse U-shaped dose-efficacy relationship, a hormesis. Old
      (27-month-old) rats given different doses of D for 1 month showed a typical
      hormetic response for antioxidant enzyme activities, indicating a significant
      increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain
      dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a
      week), but a significantly negative response with the highest dose (4
      mg/kg/inj.). Our results clearly indicate that a proper dose of D within a
      certain dose range can significantly increase the life span of rats, but that a
      greater dose becomes less effective and may actually adversely affect the life
      span of rats. A similar hormetic response for its effect on antioxidant enzyme
      activities and the parallel between the two different effects of D suggest a
      possible causal relationship between these two effects of D. The presence of this
      effective dose range of D may explain previously reported discrepancies in the
      effect of D on the life span of animals.

PMID- 16804015
TI  - Processing, lysis, and elimination of brain lipopigments in rejuvenation
      therapies.
AB  - Cerebral lipopigments (LPs)--lipofuscin and ceroid--represent a significant
      marker in postmitotic normal and pathologic aging, connected with causal and
      associated neuropathologic damage. Therefore, LP processing, lysis, and
      elimination may be the main targets in anti-aging and rejuvenation therapies. The
      regenerative neuroactive factors improve neuron supply with specific nutrients
      from plasma. They enhance the antioxidative defense, have anti-LP-poietic
      actions, stimulate brain anabolism, support energetic metabolism, and elevate the
      reduced lysosomal enzymes. In the second stage, by cytoplasm rehydration, they
      initiate the breaking up of the neuronal aggregated LP conglomerates, by
      consecutive disintegration. Then, possibly by the localized exo-endocytosis
      process between neurons and adjacent glia (especially microglia), intercellular
      LP transfer can be realized. So, therapeutically activated glia turn into brain
      garbage collectors and transporters. Therapeutic processing of glial LPs
      increases in the capillary neighborhood. Highly processed LPs, by glio
      endothelial transfer, reach capillary walls before being eliminated.
      Consequently, neuroactive therapies having these synergistic rejuvenative actions
      represent new prospects in deceleration of normal and pathological cerebral
      aging.

PMID- 16804016
TI  - Effect of dietary restriction on learning and memory impairment and histologic
      alterations of brain stem in senescence-accelerated mouse (SAM) P8 strain.
AB  - The age-associated spontaneous spongy degeneration in the brain stem of
      senescence-accelerated mouse (SAM) P8 strain has been suggested to be closely
      associated with the ability to learn and memorize. In this study, we investigated
      the effects of dietary restriction (DR) initiated from weaning on learning and
      memory and histologic changes of the brain stem in P8 and control R1 mice.
      Although no effect of DR was observed in the retention of the passive-avoidance
      response in both the P8 and R1 mice, the acquisition of the task was
      significantly improved by DR in P8 mice. On the other hand, the total area and
      number of vacuoles in the brain stem was significantly higher in ad libitum-fed
      (AD)-P8 mice than in AD-R1 mice. However, no significant effect was observed on
      the vacuole formation in the brain stem of P8 mice by DR. These observations
      suggest that the improvement of the acquisition of the task by DR in P8 mice is
      possibly due to changes in neuronal function rather than histologic alteration in
      brain stem.

PMID- 16804018
TI  - Nutraceutical supplementation: effect of a fermented papaya preparation on redox
      status and DNA damage in healthy elderly individuals and relationship with GSTM1
      genotype: a randomized, placebo-controlled, cross-over study.
AB  - Our study group consisted of 54 elderly patients without major invalidating
      diseases who were randomly divided into two fully matched groups. Group A was
      given a certified fermented papaya preparation 9 g/day by mouth, while group B
      received placebo. Treatment was carried out in a cross-over manner with a 3-month
      supplementation followed by a 6-week washout period. Blood samples were drawn at
      entry and on a monthly basis to check routine parameters, redox status, and 8
      OHdG in circulating leukocyte DNA. Polymorphism analysis of GSTM1 was carried out
      as well. The glutathune-S transferase M1 (GSTM1) genotype was null (-) in 40% and
      46% of groups A and B, respectively. GSTM1 (-) smokers had a significantly higher
      level of plasma DNA adducts and leukocytes level of 8-OHdG than their GSTM1 (+)
      counterparts (P < 0.01). There was a weak correlation between cigarettes
      smoked/day and DNA adduct (r: 0.61, P < 0.05), which also correlated with
      antioxidant concentrations, but only in GSTM1 (-) smokers (P < 0.01). The
      fermented papaya preparation (FPP)-supplemented group showed a significant
      enhancement of the antioxidant protection (P < 0.01 vs. A) within the subgroups
      with GSTM1 (-) and of plasma DNA adduct, irrespective of the GSTM1 genotype. Only
      the GSTM1 (-) subgroup was the one that, under FPP treatment, increased
      lymphocyte 8-OHdG (P < 0.01). Such preliminary data show that FPP is a promising
      nutraceutical for improving antioxidant-defense in elderly patients even without
      any overt antioxidant-deficiency state while helping explain some inconsistent
      results of prior interventional studies.

PMID- 16804017
TI  - Curcumin's biphasic hormetic response on proteasome activity and heat-shock
      protein synthesis in human keratinocytes.
AB  - Curcumin (diferuloylmethane), is a component of the yellow powder prepared from
      the roots of Curcuma longa (Zingiberaceae), also known as tumeric or turmeric. It
      is widely cultivated and used as a food ingredient in tropical areas of Asia and
      Central America. Treatment of mid-passage human epidermal keratinocytes with
      curcumin resulted in a biphasic hormetic dose-response with respect to proteasome
      activity. Curcumin treatment (up to 1 microM for 24 h) increased chymotrypsin
      like activity by 46% compared to that in untreated keratinocytes. However, higher
      concentrations of curcumin were inhibitory, and at 10 microM the proteasome
      activity decreased to 46% of its initial value. Furthermore, the preincubation of
      human keratinocytes at 43 degrees C for 1 h, followed by 24-h treatment with 3
      microM curcumin, led to an increase in heat-shock protein (hsp70 and hsp90)
      levels by 24% and 19%, respectively, and the effect was sustained at
      concentrations up to 10 microM. On the other hand, the level of the small hsp27
      was unaffected by curcumin concentrations of 0.3-1 microM, while it decreased by
      34% at 10 microM.

PMID- 16804019
TI  - Redox status impairment in liver and kidney of prematurely senescent mice:
      effectiveness of DTS phytotherapeutic compound.
AB  - T-maze test-selected prematurely senescent mice (PSM) were allocated into two
      groups: (A) those given DTS (150 mg/kg) orally for 30 days and (B) untreated PSM
      with age-matched fast T-maze performers as control. After sacrifice, the liver
      and kidney were analyzed for catalase (CAT) activity, glutathione peroxidase
      (GPx), superoxide dismutase (SOD), malondyaldehyde (MDA), and plasma thiols.
      Untreated PSM showed decreased plasma thiols and tissue level of CAT, SOD, GPx,
      with higher MDA (P < 0.01 vs. fast performers), while DTS (Denshichi-Tochiu-Sen)
      significantly improved glutathione and cysteine (P < 0.05) and tissue
      concentration of the above parameters (P < 0.05). Such preliminary data suggest
      that DTS mitigated oxidative damage in PSM, with likely action on the cytoplasm
      and mitochondrial matrix.

PMID- 16804020
TI  - A dietary supplement improves outcome in an experimental influenza model in old
      mice.
AB  - Twenty-month-old Swiss mice were allocated into three groups: (A) control; (B)
      infected group; and (C) infected but treated with 5 mg of the phytocompound MMT.
      Mice were infected intranasally with 30 microL of 75 HA viral units. MMT markedly
      blunted the nasal signs of virus infection and the febrile response. Formazan
      positive cells, lung and plasma lipoperoxides, and TNF-alpha in lung tissue
      increased during viral infection, but improvement was seen in the MMT-treated
      group (P < 0.05). MMT also normalized SOD, catalase activities, and ascorbic acid
      and determined a significant decrease of lung but not nasal viral titer, although
      nasal inflammatory infiltrate dropped significantly. MMT has potential clinical
      applications with and has an excellent safety profile even in old animals.

PMID- 16804021
TI  - Preincubation with the proteasome inhibitor MG-132 enhances proteasome activity
      via the Nrf2 transcription factor in aging human skin fibroblasts.
AB  - Strategies that lead to the upregulation of the proteasome are known to elicit
      beneficial consequences to the organism by countering oxidative stress-associated
      disorders, such as protein conformational diseases, cancer, and aging. Mild
      treatment with proteasome inhibitors has been previously demonstrated to
      stimulate proteasome activity and cellular resistance against oxidative injury.
      However, the mechanism for this action has not been clearly defined. We examined
      the role of the nuclear factor-E2-related factor 2 (Nrf2) in fibroblasts, a key
      transactivator of the antioxidant response pathway, in the regulation of the
      proteasome by its inhibitor MG-132. Here, we demonstrate that the stimulation of
      the proteasome by low levels of MG-132 can be abrogated by small interfering RNAs
      (siRNAs) targeted against Nrf2. Consistently, cells that constitutively express
      Nrf2 exhibit elevated levels of proteasome activities. We further investigate how
      its beneficial effects, that is, proteasome stimulation, are manifested in young
      and replicative-senescent cells. Our data underscore that manipulation of Nrf2 by
      the administration of pharmacologically low levels of proteasome inhibitors may
      prove to be an alternatively potent strategy for inducing long-term protective
      effects against oxidative stress.

PMID- 16804022
TI  - Exercise and hormesis: activation of cellular antioxidant signaling pathway.
AB  - Contraction-induced production of reactive oxygen species (ROS) has been shown to
      cause oxidative stress to skeletal muscle. As an adaptive response, muscle
      antioxidant defense systems are upregulated after heavy exercise. Nuclear factor
      (NF) kappaB and mitogen-activated protein kinases (MAPKs) are the major oxidative
      stress-sensitive signal transduction pathways in mammalian tissues. Activation of
      NF-kappaB signaling cascade has been shown to enhance the gene expression of
      important enzymes, such as mitochondrial superoxide dismutase (MnSOD) and
      inducible nitric oxide synthase (iNOS). MAPK activations are involved in a
      variety of cellular functions including growth, proliferation, and adaptation. We
      investigated the effect of an acute bout of exercise on NF-kappaB and MAPK
      signaling, as well as on the time course of activation, in rat skeletal muscle.
      In addition, we studied the role of ROS in the exercise-induced upregulation of
      MnSOD and iNOS, and the potential interactions of NF-kappaB and MAPK in the
      signaling of these enzymes. Our data suggest that ROS may serve as messenger
      molecules to activate adaptive responses through these redox-sensitive signaling
      pathways to maintain cellular oxidant-antioxidant homeostasis during exercise.

PMID- 16804023
TI  - Stem cells: potential therapy for age-related diseases.
AB  - Aging is associated with a progressive failing of tissues and organs of the human
      body leading to a large number of age-related diseases. Regenerative medicine is
      an emerging clinical discipline that aims to employ cellular medicines (normal
      cells, ex vivo expanded cells, or tissue-engineered organs) to restore the
      functions of damaged or defective tissues and organs and thus to "rejuvenate" the
      failing aging body. One of the most important sources for cellular medicine is
      embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with
      enormous clinical potential is the mesenchymal stem cells (MSCs) that are present
      in the bone marrow and are able to differentiate into cell types such as
      osteoblasts, chondrocytes, endothelial cells, and probably also neuron-like
      cells. Because of the ease of their isolation and their extensive differentiation
      potential, MSCs are among the first stem cell types to be introduced in the
      clinic. Some recent studies have demonstrated the possible use of MSCs in
      systemic transplantation for systemic diseases, local implantation for local
      tissue defects, as a vehicle for genes in gene therapy protocols, or to generate
      transplantable tissues and organs in tissue-engineering protocols. However,
      several challenges confront the use of these cells in the clinic, ranging from
      biological challenges (e.g., how to isolate a homogenous populations of the cells
      with specific criteria from the bone marrow and how to expand them ex vivo
      without affecting their differentiation potential) to biotechnological challenges
      (e.g., how to develop easy methods for quality control of the cellular-based
      products). While it is expected that cellular medicines will decrease the burden
      of several age-related diseases, it is not clear whether they can change the
      course of the aging process itself and thus prolong human life.

PMID- 16804024
TI  - Heat shock-induced enhancement of osteoblastic differentiation of hTERT
      immortalized mesenchymal stem cells.
AB  - Heat shock (HS)-induced stress response in human cells results in a variety of
      biological effects and is known to induce the transcription of heat-shock
      proteins, which help the cells to cope with different kinds of stress. We have
      studied the effects of HS on the differentiation of human mesenchymal stem cells
      (hMSCs) into osteoblastic cells. As a model for hMSCs we used a telomerase
      immortalized hMSC line designated hMSC-TERT. Cells were exposed to 1 h HS at 41
      degrees C, 42.5 degrees C, or 44 degrees C prior to incubation in a medium
      containing either 10(-8) M 1alpha,25-dihydroxy-vitamin-D(3) (calcitriol) or 10(
      8) M calcitriol, 50 microg/mL L-ascorbic acid, and 10 mM beta-glycerophosphate
      followed by an analysis of induction of osteoblast differentiation and the
      formation of mineralized matrix, respectively. Our results indicate that the
      exposure of cells to mild heat stress enhances the extent of differentiation of
      hMSCs by 12% to 42%. These effects are an expression of the phenomenon of mild
      stress-induced hormesis.

PMID- 16804025
TI  - Selective PPAR agonists for the treatment of type 2 diabetes.
AB  - Type 2 diabetes is a metabolic disease characterized by increased plasma glucose
      and insulin as well as dyslipidemia. If left untreated, chronic diseases will
      develop that are associated with neuropathic damage and higher mortality risk.
      Using a rational drug design, novel compounds have been developed that
      selectively activate the human PPAR receptors, leading to lessening of
      hyperglycemia and hyperinsulinemia as well as reduction of lipid levels in
      conjunction with an increase of the beneficial HDL-cholesterol. These PPAR
      agonists showed increased potency and efficacy compared to previously marketed
      insulin sensitizers. Lead compounds with desirable pharmacokinetic properties
      were chosen for further testing in several animal models. The in vivo activity of
      some synthetic ligands, capable of activating two or all three members of
      peroxisome proliferator-activated receptors (PPAR) family of receptors, suggested
      that they may have improved efficacy in type 2 diabetes therapy. Here, we briefly
      summarize the development of some novel PPAR agonists identified by our group in
      recent years.

PMID- 16804026
TI  - Alzheimer's disease pathogenesis: role of aging.
AB  - Alzheimer's disease (AD) is the chief cause of dementia, and age is its major
      risk factor. The majority of cases (90-95%) are sporadic (SAD), and the remainder
      are familial (FAD). AD is characterized by two brain lesions, intraneuronal
      fibrillary tangles and extracellular plaques. The lesions are identical in SAD
      and FAD as well as to those in persons with Down's syndrome (DS). The same
      lesions are also observed frequently in elderly non-demented individuals (E-ND).
      Both AD lesions may stem from the normal progressive increases in oxidative
      stress (OxS) throughout the body with age. Onset of dementia due to the
      accumulating lesions is around 40 years for DS, 40-60 years for FAD, over about
      65 years for SAD, while that for E-ND is unknown. The lesions are made clinically
      manifest with time by the normal increase with age of OxS, "the dementia of old
      age," or by a process specific for each AD category, which enhances the normal
      OxS so as to lower the unknown onset age of dementia for E-ND individuals to that
      associated with the AD category. A plausible process can be advanced for each AD
      category. The hypothesis suggests convenient, effective measures to prevent and
      treat, for example, by decreasing brain OxS levels with oral antioxidants such as
      lipoic or dehydroascorbic acids that are capable of passing the blood-brain
      barrier.

PMID- 16804027
TI  - RNA regulation in mammals.
AB  - Noncoding RNAs (ncRNA) are ubiquitous regulatory factors affecting gene
      expression in all organisms. In eukaryotes ncRNAs have been shown to operate on
      virtually every level of transmission of genetic information. They are implicated
      in processes that are crucial for the correct growth and development of
      multicellular organisms. Changes in their expression are often related to stress
      conditions or associated with diseases or developmental disorders.

PMID- 16804028
TI  - Quantum dot-based protein imaging and functional significance of two
      mitochondrial chaperones in cellular senescence and carcinogenesis.
AB  - Mortalin/mtHSP70 and HSP60 are heat-shock proteins that reside in multiple
      subcellular compartments, mitochondria being the dominant compartment. We present
      here biochemical evidence for their in vivo and in vitro interactions. By the use
      of quantum dots (powerful tools used for simultaneous imaging of multiple
      proteins), we visualized minute differences in the subcellular niche of these two
      proteins in normal and cancer cells. Knockdown of either of these two by shRNA
      expression plasmids caused growth arrest of osteosarcoma cells. However,
      interestingly, whereas an overexpression of mortalin extended in vitro life span
      of normal fibroblasts (TIG-1), overexpression of HSP60 was neutral. We
      demonstrate the minute differences in subcellular distribution of mortalin and
      HSP60, their involvement in tumorigenesis, and functional distinction in pathways
      involved in senescence.

PMID- 16804029
TI  - Phage-displayed antibodies for the detection of glycated proteasome in aging
      cells.
AB  - Accumulation of posttranslationally damaged proteins during aging could explain
      the decline of cell performance with age. N(epsilon)-carboxymethyllysine (CML) is
      the major glycation product on damaged proteins, causing dysfunction and cross
      linking. The proteasome, a multicatalytic degradation complex, is one of the
      pathways for eliminating damaged proteins, and thus regulating their accumulation
      within the cell. However, the proteinase activities of the proteasome decline
      during aging. This may be due to posttranslational modifications of the subunits
      forming the proteasome complex. Using phage display technology, we have selected
      16 single-chain variable fragments (scFv) recognizing the CML-modified alpha7
      subunit of the proteasome. Using one of them, Ab3, we have observed a five-fold
      increase of CML-alpha7 in old human skin fibroblasts in comparison with young
      fibroblasts and telomerase-immortalized bone marrow cells (hTERT-BMCs).

PMID- 16804030
TI  - Techniques used in studies of age-related DNA methylation changes.
AB  - Epigenetic modification of CpG islands (CGIs) in promoter regions is an important
      regulatory mechanism of gene expression in eukaryotic cells. Hypermethylation of
      CGIs may silence a gene, whereas hypomethylation of previously methylated CGIs
      allows gene expression. The pattern of methylation is cell-type-specific and
      established during development of the organisms. Changes in the methylation
      pattern have been found in all cancer forms and in aging cells. The epigenetic
      related alternations of gene expression status may significantly contribute to
      the initiation and maintenance of malignant growth. Cancer incidence increases
      dramatically with age and correlates strongly with age-related methylation
      changes. Many techniques have been developed to analyze the genome-wide
      methylation content and the methylation status of specific loci. The majority of
      methylation screening protocols utilizes methylation-sensitive endonuclease
      digestion or bisulfite treatment of the template followed by subsequent PCR
      amplification of a specific sequence. All methods either examine only one
      specific DNA sequence at a time, or provide limited genomic information on the
      screened sequences. The principle of our new approach is to combine methylation
      sensitive enzyme digestion with the comparative genomic hybridization (CGH)
      technique to develop an array-based method to screen the entire genome for
      changes of methylation pattern. The new technique will serve as an efficient tool
      in understanding the nature of epigenetic changes and their significance to the
      aging process and cancer development.

PMID- 16804031
TI  - Geroprotection by glycerol: insights to its mechanisms and clinical potentials.
AB  - Chaperones, particularly the heat-shock proteins, are considered as key players
      in the maintenance of protein homeostasis and are associated with longevity and
      cellular immortalization. In this study, we investigated the geroprotective
      activity of the chemical chaperone glycerol. Glycerol showed significant
      chaperoning activity in refolding heat-denatured luciferase in vivo and in
      protecting cells from heat stress-induced cytotoxicity. This was accompanied by
      decrease in p53, an upregulation of a stress chaperone mortalin/mtHsp70, and an
      increase in proteasome activity in the presence of oxidative stress.

PMID- 16804032
TI  - Age-dependent effects of in vitro radiofrequency exposure (mobile phone) on CD95+
      T helper human lymphocytes.
AB  - Recent studies on "nonthermal" effects of mobile phone radiofrequency (RF)
      suggest that RF can interact with cellular functions and molecular pathways. To
      study the possible RF effects on human lymphocyte activation, we analyzed CD25,
      CD95, CD28 molecules in unstimulated and stimulated CD4+ e CD8+ T cells in vitro.
      Peripheral blood mononuclear cells (PBMCs) from young and elderly donors were
      exposed or sham-exposed to RF (1,800 MHz, Specific Absorption Rate 2 W/kg) with
      or without mitogenic stimulation. No significant changes in the percentage of
      these cell subsets were found between exposed and sham-exposed lymphocytes in
      both young and elderly donors. Nevertheless, after RF exposure we observed a
      slight, but significant, downregulation of CD95 expression in stimulated CD4+ T
      lymphocytes from elderly, but not from young donors. This age-related result is
      noteworthy given the importance of a such molecule in regulation of the immune
      response.

PMID- 16804033
TI  - Severe acute respiratory syndrome (SARS): development of diagnostics and
      antivirals.
AB  - The previously unknown coronavirus that caused severe acute respiratory syndrome
      (SARS-CoV) affected more than 8,000 persons worldwide and was responsible for
      more than 700 deaths during the first outbreak in 2002-2003. For reasons unknown,
      the SARS virus is less severe and the clinical progression a great deal milder in
      children younger than 12 years of age. In contrast, the mortality rate can exceed
      50% for persons at or above the age of 60. As part of the Sino-European Project
      on SARS Diagnostics and Antivirals (SEPSDA), an immune phage-display library is
      being created from convalescent patients in a phagemid system for the selection
      of single-chain fragment variables (scFv) antibodies recognizing the SARS-CoV.

PMID- 16804034
TI  - Re: "Cellular phones, cordless phones, and the risks of glioma and meningioma
      (Interphone Study Group, Germany)".

PMID- 16804036
TI  - The effect of androgen blockade on granulosa cell estradiol production after
      follicle-stimulating hormone stimulation in women with polycystic ovary syndrome.
AB  - CONTEXT: Previously, we have shown that women with polycystic ovary syndrome
      (PCOS) exhibit an exaggerated serum estradiol (E(2)) response to recombinant
      human FSH (rhFSH) (150 IU) compared with similarly treated normal women. This
      enhanced granulosa cell responsiveness is consistent with excessive follicular
      development after gonadotropin therapy and the corresponding risk of ovarian
      hyperstimulation syndrome. In vitro studies have shown that granulosa cells
      treated with androgens display greater FSH-induced E(2) production than untreated
      cells, suggesting a role for androgens in granulosa cell responsiveness. MAIN
      OBJECTIVE: This study was conducted to determine whether blockade of androgen
      action in PCOS women by administration of the antiandrogen flutamide would alter
      E(2) responses to rhFSH. DESIGN: We conducted a prospective cohort study.
      SUBJECTS AND SETTING: We studied 11 women with PCOS at an institutional general
      clinical research center. INTERVENTION: On study d 1, each subject received 150
      IU rhFSH iv. Frequent blood samples were obtained over 24 h. After completion of
      rhFSH stimulation, each subject was treated with flutamide, 125 mg, twice daily,
      for 6 wk. Thereafter, the rhFSH stimulation test was repeated. MAIN OUTCOME
      MEASURES: Baseline and stimulated E(2) levels before and after treatment were
      assayed. RESULTS: Mean baseline and maximally stimulated E(2), integrated E(2)
      response, and fold change in E(2) were not different before and after treatment.
      Levels of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone,
      estrone, and SHBG before and after treatment were unchanged. Baseline
      dehydroepiandrosterone sulfate levels declined significantly after flutamide
      therapy. CONCLUSION: These findings indicate that in women with PCOS, the E(2)
      hyperresponsiveness to FSH may not be attributable to increased circulating
      androgens.

PMID- 16804037
TI  - Low-dose rosiglitazone exerts an antiinflammatory effect with an increase in
      adiponectin independently of free fatty acid fall and insulin sensitization in
      obese type 2 diabetics.
AB  - BACKGROUND: We have previously demonstrated an early and potent antiinflammatory
      effect of troglitazone and rosiglitazone. HYPOTHESIS: Because inflammatory
      mediators interfere with insulin signal transduction, we have now hypothesized
      that rosiglitazone exerts an initial antiinflammatory effect independently of its
      metabolic actions including the suppression of the plasma concentration of free
      fatty acids (FFAs), insulin, and glucose after which insulin sensitization
      occurs. PATIENT AND METHODS: Fourteen patients with type 2 diabetes were included
      in the study. Eight patients were given 2 mg daily of rosiglitazone for 6 wk,
      whereas the other six patients were given a placebo for the same period. RESULTS:
      After a 2-mg dose of rosiglitazone, plasma FFAs, insulin, and glucose
      concentrations and homeostasis model assessment of insulin resistance did not
      change. Plasma C-reactive protein, serum amyloid A, and matrix metalloproteinase
      concentrations fell significantly at wk 1 and continued to be significantly lower
      than the baseline levels by 25, 29, and 24%, respectively, at wk 6. Leukocyte
      count was significantly lower at wk 6 after rosiglitazone, whereas there was no
      change in the control group. Plasma adiponectin concentrations increased
      significantly at wk 2 and continued to increase during the treatment period with
      rosiglitazone. Resistin concentrations fell significantly by 10% at wk 6 only.
      There were no changes in any of these indices in the placebo group. CONCLUSIONS:
      A low dose of rosiglitazone exerts an early and potent antiinflammatory effect
      with an increase in adiponectin and a fall in resistin concentrations without
      causing any metabolic changes (fall in plasma glucose, FFAs, and insulin
      concentrations) over a 6-wk period. The increase in adiponectin and the decrease
      in resistin after rosiglitazone are thus related primarily to its
      antiinflammatory effects rather than its metabolic actions. These observations
      have implications in relation to the mode of action of this drug as an insulin
      sensitizing agent and also its use as a potential antiinflammatory and
      antiatherogenic drug in the future.

PMID- 16804038
TI  - Estradiol potentiates ghrelin-stimulated pulsatile growth hormone secretion in
      postmenopausal women.
AB  - CONTEXT: Ghrelin and an estrogen-rich milieu individually amplify pulsatile GH
      secretion by increasing the amount of hormone released per burst. However, how
      these distinct agonists interact in controlling pulsatile GH output is not known.
      OBJECTIVE: The objective of the study was to test the hypothesis that elevated
      estradiol (E(2)) concentrations potentiate hypothalamo-pituitary responses to a
      near-physiological ghrelin stimulus. DESIGN: This was a double-blind, placebo
      controlled, prospectively randomized, parallel-cohort study. SETTING: The study
      was conducted at an academic medical center. SUBJECTS: Twenty-one postmenopausal
      women participated in the study. INTERVENTIONS: Eleven subjects received placebo
      (Pl) and 10 others E(2) transdermally in escalating doses over 3 wk to mimic late
      follicular-phase E(2) concentrations. Saline or a submaximally stimulatory amount
      of ghrelin (0.3 microg/kg) was infused iv on separate randomly ordered mornings
      fasting after 17-21 d of Pl or E(2) administration. OUTCOMES: Outcomes included
      serum concentrations of E(2), ghrelin, GH, IGF-I, IGF binding protein (IGFBP)-1
      and IGFBP-3, and the estimated mass and waveform of stimulated GH secretory
      bursts. RESULTS: Administration of E(2) yielded late follicular-phase E(2)
      concentrations. Compared with Pl, E(2) did not alter ghrelin concentrations but
      reduced IGF-I and IGFBP-3 and elevated IGFBP-1 concentrations. Compared with
      saline, ghrelin infusion amplified pulsatile GH secretion by 7.1-fold (P < 0.01).
      The effect of E(2) alone was 2.0-fold placebo and that of combined ghrelin/E(2)
      10.4-fold (P < 0.01). Ghrelin and E(2) accelerated initial GH release
      individually but nonadditively by more than 2-fold (P < 0.01). CONCLUSIONS:
      Estrogen augments ghrelin's near-physiological stimulation of pulsatile GH
      secretion and mimics ghrelin's acceleration of initial GH release. Thus, we
      hypothesize that estrogen and a GH secretagogue act via independent as well as
      convergent mechanisms.

PMID- 16804039
TI  - Thyroid function is intrinsically linked to insulin sensitivity and endothelium
      dependent vasodilation in healthy euthyroid subjects.
AB  - CONTEXT: Levels of TSH respond to fluctuations in serum free T(4) (fT(4)) but
      remain in a very narrow individual range. There exists current controversy
      regarding the upper limit of normal serum TSH values above which treatment should
      be indicated. OBJECTIVE: We aimed to study whether the individually determined
      fT(4)-TSH relationship was associated with plasma lipids, insulin sensitivity,
      and endothelial dysfunction in healthy subjects with strictly normal thyroid
      function according to recent recommendations (0.3-3.0 mU/liter). DESIGN: This was
      a cross-sectional study. SETTING: The study consisted of a cohort of healthy men
      from the general population (n = 221). MAIN OUTCOME MEASURES: Oral glucose
      tolerance, insulin sensitivity (S(I), minimal model), endothelium-dependent
      vasodilation (high-resolution ultrasound), and plasma lipids were measured in
      relation to thyroid function tests. RESULTS: Both serum TSH and fT(4).TSH product
      were positively associated with fasting and postload insulin concentration and
      negatively with S(I). After body mass index stratification, these associations
      were especially significant among lean subjects. Serum TSH and fT(4).TSH product
      also correlated positively with fasting triglycerides and negatively with high
      density lipoprotein cholesterol. In a multiple linear regression analysis, age (P
      = 0.007) and S(I) (P = 0.02) but not body mass index, fasting triglycerides, or
      serum high-density lipoprotein concentration contributed independently to 3.7 and
      3.3%, respectively, of the variance in fT(4).TSH. Those subjects over the median
      of fT(4).TSH showed reduced endothelium-dependent vasodilation. CONCLUSIONS:
      Thyroid function tests are intrinsically linked to variables of insulin
      resistance and endothelial function. It is possible that underlying factors lead
      simultaneously to increased serum TSH, insulin resistance, ensuing dyslipidemia,
      and altered endothelial function even within current normal TSH levels.

PMID- 16804040
TI  - Changes in serum insulin-like factor 3 during normal male puberty.
AB  - CONTEXT: Insulin-like factor 3 (INSL3) is produced by the Leydig cells, and in
      adults, its secretion is dependent on the state of differentiation of these
      cells, which, in turn, is dependent on LH. However, the secretion and regulation
      of INSL3 during puberty is unknown. OBJECTIVE: Our objective was to evaluate
      INSL3 concentrations during normal male puberty and the relation of INSL3 to LH,
      FSH, and testosterone. DESIGN AND SETTING: We conducted a cross-sectional study
      from January to December 2005 at academic clinics. PATIENTS: Participating in the
      study were 75 healthy male subjects aged 9.5-17.5 yr, homogeneously distributed
      into five pubertal groups of 15 according to Tanner stages. MAIN OUTCOME
      MEASURES: We assessed mean testicular volume and LH, FSH, testosterone, and INSL3
      concentrations in relation to age and pubertal stage. RESULTS: We observed an
      increase of INSL3 and LH levels from Tanner stage 2 to 4, and an increase of FSH
      from stage 2 to 3. Testosterone levels increased from stage 3 to 4. No
      differences were seen for all measured hormones between stages 4 and 5. The
      increase in INSL3 seemed therefore to anticipate the increase in testosterone.
      However, INSL3 plasma concentrations at pubertal stages 4 and 5 are about one
      fourth of adult levels, whereas FSH, LH, and testosterone reached adult levels by
      stage 4. Positive significant correlations were found between INSL3 and LH for
      all pubertal stages. CONCLUSIONS: This study provides information on the
      physiological dynamics of INSL3, showing that the serum concentrations of this
      hormone increased progressively throughout puberty under the differentiating
      action of LH on Leydig cells. INSL3 is therefore confirmed to represent a marker
      of Leydig cell differentiation and function. However, a prolonged exposure to LH
      seems to be necessary to reach INSL3 concentrations of adults. A possible use of
      INSL3 in puberty disorders is promising.

PMID- 16804041
TI  - Mosaicism of a thyroid hormone receptor-beta gene mutation in resistance to
      thyroid hormone.
AB  - CONTEXT: Heterozygous mutations in thyroid hormone receptor-beta (TRbeta) gene
      are the cause of resistance to thyroid hormone (RTH) in more than 85% of families
      having the syndrome. In 23% of the families, TRbeta gene mutations occur de novo.
      Of the 141 families with RTH investigated by us, 21 (15%) had no TRbeta gene
      mutations detectable by sequencing from genomic DNA (gDNA) or cDNA (non-TR RTH).
      OBJECTIVE: The objective of the study was to investigate the genotype of a family
      with RTH and correlate it to the phenotype. DESIGN: The DNA was isolated from
      different tissues, and the sequence of the TRbeta gene was determined. Clinical
      studies involved the administration of incremental doses of T(3). SETTING: The
      study was conducted at a referral pediatric endocrinology clinic in Turkey and an
      academic medical center in the United States. MAIN OUTCOME AND MEASURES:
      Measurement included markers of thyroid hormone action and sequencing of TRbeta
      revealing a R338W mutation. Patients and Family: We studied two siblings with
      short stature, panic disorder, psychosis, and high free iodothyronine
      concentrations with nonsuppressed TSH and their father with similar thyroid
      function tests without growth or psychiatric abnormalities. RESULTS: Direct
      sequencing of gDNA obtained from the father's leukocytes, buccal mucosa cells,
      and prostate tissue showed less amplification of the mutant allele (R338W) than
      the normal allele as confirmed by PCR/restriction fragment length polymorphism
      analysis. No sequence abnormalities were detected in gDNA from fibroblasts.
      Similar results were found in mRNA from the leukocytes and fibroblasts. The
      sensitivity of various tissues to thyroid hormone was not uniform. The progeny
      had equal amounts of mutant and wild-type gDNA in leukocytes and skin.
      CONCLUSIONS: The father has a mosaicism for the R338W mutation as it was present
      in some cell lineages, including his germline, because it was transferred to his
      children but not in fibroblasts. This indicates that the mutation occurred de
      novo in early embryonic life. Here is the first report of mosaicism in RTH. The
      possibility of mosaicism should be considered in subjects with RTH without
      apparent mutations in the TRbeta gene.

PMID- 16804042
TI  - The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect
      of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH
      deficient small-for-gestational-age children: results from a two-year controlled
      prospective study in 170 Spanish patients.
AB  - CONTEXT: The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted/full-length GHR) has
      recently been associated with responsiveness to GH therapy. OBJECTIVE: The
      objective of the study was to evaluate whether the d3/fl-GHR genotypes influence
      the intensity of spontaneous and/or GH therapy-stimulated growth in small-for
      gestational-age (SGA) patients. DESIGN: This was a 2-yr prospective, controlled,
      randomized trial. SETTING: Thirty Spanish hospitals participated. Auxologic and
      GH secretion evaluation was hospital based, whereas molecular analyses and
      auxologic data computation were centralized. PATIENTS: Patients included 170
      short SGA children: 140 remained prepubertal and 30 entered puberty during the
      second follow-up year. INTERVENTION: Eighty-six were treated with GH (66
      microg/kg.d) for 2 yr and 84 were not treated. MAIN OUTCOME MEASURES: Previous
      and 2-yr follow-up auxologic data were recorded at each hospital, d3/fl-GHR
      genotypes determined, and data analyzed for patients who remained prepubertal
      (group 1, 68 GH treated and 72 non-GH treated) and for all the patients (group
      2). RESULTS: In group 1 GH-treated patients, growth velocity, and height-sd score
      during the first and second years, total 2-yr height gain (18.5 +/- 2.4 cm in
      d3/d3; 18.4 +/- 2.6 in d3/fl; 19.5 +/- 2.3 in fl/fl), Delta 2-yr height increase
      (9.1 +/- 2.4 cm in d3/d3; 9.4 +/- 3.0 in d3/fl; 10.4 +/- 2.1 in fl/fl), first
      year growth prediction and studentized residual values (0.08 +/- 1.26 in d3/d3;
      0.28 +/- 1.21 in d3/fl; 0.67 +/- 0.95 in fl/fl) did not differ among the d3/fl
      GHR genotypes. In group 1 non-GH-treated patients, neither growth velocity nor
      height-sd score changed significantly, and values were similar in each d3/fl-GHR
      genotype. Results in all patients (group 2) were similar to those in group 1.
      CONCLUSIONS: In short non-GH-deficient SGA children, both spontaneous growth rate
      and responsiveness to 66 microg/k.d GH therapy were similar for each d3/fl-GHR
      genotype carried.

PMID- 16804043
TI  - Risk of fracture in women with type 2 diabetes: the Women's Health Initiative
      Observational Study.
AB  - CONTEXT: Some but not all studies have shown higher rates of fracture in
      individuals with type 2 diabetes. OBJECTIVE: The objective of the study was to
      determine the risk of fracture in postmenopausal women with type 2 diabetes and
      determine whether risk varies by fracture site, ethnicity, and baseline bone
      density. DESIGN, SETTING, AND PARTICIPANTS: Women with clinically diagnosed type
      2 diabetes at baseline in the Women's Health Initiative Observational Cohort, a
      prospective study of postmenopausal women (n = 93,676), were compared with women
      without diagnosed diabetes and risk of fracture overall and at specific sites
      determined. MAIN OUTCOME MEASURES: All fractures and specific sites separately
      (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow;
      lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD)
      in a subset also was measured. RESULTS: The overall risk of fracture after 7 yr
      of follow-up was higher in women with diabetes at baseline after controlling for
      multiple risk factors including frequency of falls [adjusted relative risk (RR)
      1.20, 95% confidence interval (CI) 1.11-1.30]. In a subsample of women with
      baseline BMD scores, women with diabetes had greater hip and spine BMD. The
      elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot;
      spine/tailbone) among black women (RR 1.33, 95% CI 1.00-1.75) and women with
      increased baseline bone density (RR 1.26, 95% CI 0.96-1.66). CONCLUSION: Women
      with type 2 diabetes are at increased risk for fractures. This risk is also seen
      among black and non-Hispanic white women after adjustment for multiple risk
      factors including frequent falls and increased BMD (in a subset).

PMID- 16804044
TI  - Psychological well-being correlates with free thyroxine but not free 3,5,3'
      triiodothyronine levels in patients on thyroid hormone replacement.
AB  - CONTEXT AND OBJECTIVE: An association between mood disorders and overt thyroid
      dysfunction is well established, but there are few data on the potential for
      thyroid hormone levels closer to the reference range to correlate with
      psychological well-being. DESIGN, SETTING, AND PATIENTS: We analyzed the
      relationship between psychological well-being and free T(4) (fT4), free T(3)
      (fT3), TSH, and total rT(3) in 697 patients on thyroid hormone replacement
      therapy at entry to a randomized, controlled trial of combined T(4) and T(3)
      replacement therapy. All patients were on 100 mug or more T(4). INTERVENTIONS AND
      MAIN OUTCOME MEASURES: Psychological well-being was assessed with General Health
      Questionnaire-12 (GHQ-12), Thyroid Symptom Questionnaire, and Hospital Anxiety
      and Depression Scale. RESULTS: fT(4) and TSH showed a strong correlation with GHQ
      12 scores (fT4 - b: -0.16, P = 0.005; TSH - b: 0.663, P = 0.04). No correlations
      were seen between the GHQ scores and fT3 (b: 0.318, P = 0.275), rT(3) (b: 0.095,
      P = 0.95), rT(3) to fT4 ratio (b: 71.83, P = 0.09) or fT3 to rT(3) ratio (b:
      0.05, P = 0.32). The correlations remained when the data set was limited to
      patients with TSH in the range 0.3-4.0 mIU/liter. Similar correlations were seen
      with the Thyroid Symptom Questionnaire, although not with the Hospital Anxiety
      and Depression Scale scores. CONCLUSIONS: Differences in fT4 and TSH
      concentration, even within the reference range, may be a determinant of
      psychological well-being in treated hypothyroid patients although not necessarily
      with symptoms typical of anxiety or depression.

PMID- 16804045
TI  - The A645D mutation in the hinge region of the human androgen receptor (AR) gene
      modulates AR activity, depending on the context of the polymorphic glutamine and
      glycine repeats.
AB  - BACKGROUND: Sufficient androgen receptor (AR) activity is crucial for normal male
      sexual differentiation. Here we report on two unrelated 46, XY patients suffering
      from undervirilization and genital malformations. Both patients had a short
      polyglycine (polyG) repeat of 10 residues and a relatively long polyglutamine
      (polyQ) repeat of 28 and 30 residues within the transactivation domain of the AR.
      In addition, they also harbor a rare A645D substitution. OBJECTIVE: We made a set
      of AR expression plasmid constructs with varying polyQ and polyG tract sizes in
      context with or without the A645D substitution and analyzed their in vitro
      transactivation capacity in transfected CHO cells. RESULTS: We found that a short
      polyG repeat downmodulated AR activity to approximately 60-65% of the wild-type
      receptor. This effect was aggravated by A645D in context of a long polyQ repeat
      to less than 50% activity. In contrast, in the context of a short polyQ and a
      short polyG repeat, the A645D mutation rescues AR activity to almost wild-type
      levels, demonstrating a contradictory effect of this mutation, depending on the
      size of the polymorphic repeats. CONCLUSIONS: A combination of a short polyG
      repeat with a long polyQ repeat and an A645D substitution might contribute to the
      development of virilization disorders and explain the observed phenotypes of our
      patients as a form of androgen insensitivity. The whole recreation of AR sequence
      variations including individual polymorphic repeat sizes could unravel possible
      interference of mutations and variations on AR activity by in vitro transfection.

PMID- 16804046
TI  - Anti-Mullerian hormone levels in the spontaneous menstrual cycle do not show
      substantial fluctuation.
AB  - CONTEXT: Anti-Mullerian hormone (AMH), a quantitative marker for ovarian reserve,
      has been suggested to be independent of the classical endocrine fluctuations of
      the menstrual cycle. OBJECTIVE: The objective of the study was to determine
      whether AMH levels are constant throughout the menstrual cycle, compared with
      those of FSH, LH, and estradiol. DESIGN/PATIENTS: Frequent blood sampling was
      performed in 44 fertile, regularly cycling, female volunteers during one full
      menstrual cycle. SETTING: The study was conducted at a university hospital. MAIN
      OUTCOME MEASURES: AMH, FSH, LH, and estradiol measurements were allocated to one
      of seven cycle phases, and a multilevel analysis was performed. Consistent
      fluctuation patterns were tested by fitting sine patterns to the data. Finally,
      the frequency in which randomly selected individual samples would remain in one
      of five preset level categories (quintiles) for each of the variables was
      studied. RESULTS: A sine pattern fitted to the AMH data was not statistically
      significant (P = 0.40). In contrast, sine patterns for FSH, LH, and estradiol
      were highly significant. Comparing the seven cycle phases, no significant
      differences could be observed between phase-specific AMH levels (P = 0.06).
      Repeated selection of AMH samples for each individual showed that in 71.5% of
      selections, AMH values remained in the same quintile, whereas in 27.9% values
      fell in an adjacent quintile. CONCLUSIONS: AMH levels measured through a full
      menstrual cycle did not show consistent fluctuation patterns in contrast to
      levels of FSH, LH, and estradiol. Furthermore, random fluctuations were small,
      indicating that AMH can be relied on as a cycle-independent marker for ovarian
      reserve.

PMID- 16804047
TI  - Weight-adjusted genome scan analysis for mapping quantitative trait Loci for
      menarchal age.
AB  - CONTEXT: Twin and family studies indicate that genetic factors contribute to the
      variability of age at menarche (AAM), a multifactorial trait of major importance
      to human reproductive success. Individual variability of premenarcheal fatness is
      known to be an important determinant of AAM. OBJECTIVE: The objective of the
      study was mapping quantitative trait loci (QTLs) for AAM. DESIGN AND METHODS: AAM
      was assessed in 98 sister pairs of recent European ancestry whose growth charts
      were available. There was a negative correlation between menarcheal body weight
      sd score (SDS) and AAM (r = 0.47, P < 0.0001). We designed a genome scan approach
      and used the variance components model implemented in Merlin for quantitative
      traits to evaluate linkage of AAM and AAM adjusted for menarcheal weight SDS to
      418 genome-wide microsatellites. RESULTS: Multipoint linkage analysis for AAM
      revealed nominal QTLs defined by LOD scores between 1.06 and 1.69 on chromosomes
      1p, 1q, 7p, 8q, 16p, 19q, and 20q. The genome scan for AAM adjusted for
      menarcheal weight SDS revealed several QTLs with strongly suggestive LOD scores
      in 16q21 (LOD = 3.33), 16q12 (LOD = 3.12), and 8p12 (LOD = 2.18) and a number of
      other nominally significant QTLs yet viewed as hypothetical. CONCLUSIONS: We
      found several regions that may contain determinants of AAM, but there is still a
      long series of steps to confirm these QTLs and identify the genomic polymorphisms
      implicated in AAM variability.

PMID- 16804048
TI  - Diet/Exercise versus pioglitazone: effects of insulin sensitization with
      decreasing or increasing fat mass on adipokines and inflammatory markers.
AB  - BACKGROUND: Plasma adipokine concentrations are variably related to
      fatness/insulin resistance and may act via endocrine mechanisms. We assessed the
      relationship among plasma adipokine concentrations and their relationship with
      insulin sensitivity and body composition in obese adults before and after insulin
      sensitization accomplished using diet/exercise or pioglitazone. METHODS: Plasma
      adipokine concentrations, insulin sensitivity, and body composition were assessed
      in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19
      wk of diet/exercise or 30 mg/d pioglitazone. RESULTS: Diet/exercise reduced body
      fat and visceral fat and improved insulin sensitivity parameters; pioglitazone
      improved insulin sensitivity to a similar degree but increased body fat.
      Adiponectin increased more after pioglitazone (4770 +/- 487 vs. 8351 +/- 693.6
      ng/ml, P < 0.001) than after diet/exercise (4704 +/- 367 to 5426 +/- 325.3 ng/ml,
      P < 0.01), whereas TNFalpha, IL-6, and resistin did not change. C-reactive
      protein decreased with diet/exercise. Adipokine concentrations were not
      correlated with each other at baseline or after insulin sensitization, except
      TNFalpha and IL-6 (r = 0.43, P < 0.05); IL-6 was inversely correlated with
      resistin. Only adiponectin was correlated (P < 0.05) with indices of insulin
      sensitivity. Adiponectin concentrations were inversely correlated with visceral
      fat and with sc fat depots in men but positively correlated with sc fat in women.
      CONCLUSION: Plasma adipokine concentrations were not consistently interrelated,
      and only adiponectin displayed the expected relationship with insulin sensitivity
      and sensitization. These findings do not support an endocrine role for resistin,
      TNFalpha, and IL-6 in mediating changes in insulin resistance after diet/exercise
      or pioglitazone.

PMID- 16804049
TI  - Haplotypes defined by promoter and intron 1 polymorphisms of the COLIA1 gene
      regulate bone mineral density in women.
AB  - CONTEXT: The COLIA1 gene is a strong candidate for susceptibility to
      osteoporosis. The causal genetic variants are currently unclear, but the most
      likely are functional polymorphisms in the promoter and intron 1 of COLIA1.
      OBJECTIVE: The objective of the study was to determine whether promoter and
      intron 1 polymorphisms of COLIA1 or haplotypes defined by these polymorphisms
      regulate bone mineral density (BMD) in women. DESIGN: This was a population-based
      association study involving 3270 women from the United Kingdom who took part in a
      regional osteoporosis screening program. MAIN OUTCOME MEASURES: BMD at the lumbar
      spine (LS-BMD) and femoral neck (FN-BMD) was measured on two occasions
      approximately 6 yr apart, in relation to polymorphisms and haplotypes defined by
      polymorphisms within the COLIA1 intron 1 (+1245G/T; rs1800012) and promoter (
      1997G/T; rs1107946; -1663IndelT; rs2412298). RESULTS: The polymorphisms were in
      strong linkage disequilibrium, and three haplotypes accounted for more than 95%
      of alleles at the COLIA1 locus. The individual polymorphisms were associated with
      BMD, but the most consistent associations were with haplotypes defined by all
      three polymorphisms. Homozygote carriers of haplotype 2 (-1997G/-1663delT/+1245T)
      had reduced BMD at baseline (P = 0.007 for LS-BMD; P = 0.008 for FN-BMD), whereas
      homozygotes for haplotype 3 (-1997T/-1663insT/+1245G) had increased BMD (P =
      0.007 for LS-BMD). Similar associations were observed at follow-up for haplotype
      3, but the association with haplotype 2 was weaker due to increased uptake of
      hormone replacement therapy in homozygotes for this haplotype. CONCLUSIONS: Two
      haplotypes defined by polymorphisms in the 5' flank of the COLIA1 regulate BMD in
      a bidirectional manner in women.

PMID- 16804050
TI  - Effects of dehydroepiandrosterone and atamestane supplementation on frailty in
      elderly men.
AB  - BACKGROUND: It has been suggested that the age-related decline of androgens in
      men plays a distinct role in the development of several aspects of frailty.
      Therefore, hormone replacement might improve the course of frailty by increasing
      lean body mass and muscle strength, decreasing fat mass, and improving the
      subjective quality of life. OBJECTIVE: The objective of the study was to assess
      whether hormone replacement with dehydroepiandrosterone (DHEA) and/or atamestane
      might improve the course of frailty. DESIGN: This was a double-blind, randomized,
      controlled trial. SETTING: The study was conducted in the general community.
      PARTICIPANTS: Participants included 100 nonhospitalized, nondiseased,
      independently living men, aged 70 yr and over with low scores on strength tests.
      Seventeen participants did not complete the trial. INTERVENTION: Subjects were
      randomly assigned to one of four intervention arms: atamestane (100 mg/d) and
      placebo, DHEA (50 mg/d) and placebo, a combination of atamestane (100 mg/d) and
      DHEA (50 mg/d), or two placebo tablets for 36 wk. MAIN OUTCOME MEASURES: Physical
      frailty was measured by means of a specific test battery, including isometric
      grip strength, leg extensor power, and physical performance. RESULTS: The
      randomization was successful, and 83 (83%) men completed the intervention. There
      were no differences between the treatment arms and placebo group in any of the
      outcome measurements after intervention. CONCLUSIONS: The results of this double
      blind, randomized trial do not support the hypothesis that hormone replacement
      with DHEA and/or atamestane might improve the course of frailty.

PMID- 16804051
TI  - Regulatory T cells in human autoimmune thyroid disease.
AB  - CONTEXT: T regulatory cells have a key role in the pathogenesis of autoimmune
      diseases in different animal models. However, less information is available
      regarding these cells in human autoimmune thyroid diseases (AITD). OBJECTIVE: The
      objective of the study was to analyze different regulatory T cell subsets in
      patients with AITD. DESIGN: We studied by flow cytometry and immunohistochemistry
      different T regulatory cell subsets in peripheral blood mononuclear cells (PBMCs)
      and thyroid cell infiltrates from 20 patients with AITD. In addition, the
      function of T(REG) lymphocytes was assessed by cell proliferation assays.
      Finally, TGF-beta mRNA in thyroid tissue and its in vitro synthesis by thyroid
      mononuclear cells (TMCs) was determined by RNase protection assay and
      quantitative PCR. RESULTS: PBMCs from AITD patients showed an increased percent
      of CD4+ lymphocytes expressing glucocorticoid-induced TNF receptor (GITR), Foxp3,
      IL-10, TGF-beta, and CD69 as well as CD69+CD25(bright), CD69+TGF-beta, and
      CD69+IL-10+ cells, compared with controls. TMCs from these patients showed an
      increased proportion of CD4+GITR+, CD4+CD69+, and CD69+ cells expressing
      CD25(bright), GITR, and Foxp3, compared with autologous PBMCs. Furthermore, a
      prominent infiltration of thyroid tissue by CD69+, CD25+, and GITR+ cells, with
      moderate levels of Foxp3+ lymphocytes, was observed. The suppressive function of
      peripheral blood T(REG) cells was defective in AITD patients. Finally, increased
      levels of TGF-beta mRNA were found in thyroid tissue, and thyroid cell
      infiltrates synthesized in vitro significant levels of TGF-beta upon stimulation
      through CD69. CONCLUSIONS: Although T regulatory cells are abundant in inflamed
      thyroid tissue, they are apparently unable, in most cases, to downmodulate the
      autoimmune response and the tissue damage seen in AITD.

PMID- 16804052
TI  - A putative acyl-CoA-binding protein is a major phloem sap protein in rice (Oryza
      sativa L.).
AB  - The N-terminal amino-acid sequence of a major rice phloem-sap protein, named
      RPP10, was determined. RPP10 is encoded by a single gene in the rice genome. Its
      complete amino-acid sequence, predicted from the corresponding rice full-length
      cDNA, showed high similarity to plant acyl-CoA-binding proteins (ACBPs). Western
      blot analysis using anti-ACBP antiserum revealed that putative ACBP is abundant
      in the phloem sap of rice plants, and is also present in sieve-tube exudates of
      winter squash (Cucurbita maxima), oilseed rape (Brassica napus), and coconut palm
      (Cocos nucifera). These findings give rise to the idea that ACBP may involve
      lipid metabolism and regulation in the phloem.

PMID- 16804053
TI  - Mutant identification and characterization of the laccase gene family in
      Arabidopsis.
AB  - Laccases, EC 1.10.3.2 or p-diphenol:dioxygen oxidoreductases, are multi-copper
      containing glycoproteins. Despite many years of research, genetic evidence for
      the roles of laccases in plants is mostly lacking. In this study, a reverse
      genetics approach was taken to identify T-DNA insertional mutants (the SALK
      collection) available for genes in the Arabidopsis laccase family. Twenty true
      null mutants were confirmed for 12 laccase genes of the 17 total laccase genes
      (AtLAC1 to AtLAC17) in the family. By examining the mutants identified, it was
      found that four mutants, representing mutations in three laccase genes, showed
      altered phenotypes. Mutants for AtLAC2, lac2, showed compromised root elongation
      under PEG-induced dehydration conditions; lac8 flowered earlier than wild-type
      plants, and lac15 showed an altered seed colour. The diverse phenotypes suggest
      that laccases perform different functions in plants and are not as genetically
      redundant as previously thought. These mutants will prove to be valuable
      resources for understanding laccase functions in vivo.

PMID- 16804054
TI  - Composition of the plant nuclear envelope: theme and variations.
AB  - The nuclear envelope is the hallmark of all eukaryotic cells, separating the
      nucleoplasm from the cytoplasm. At the same time, the nuclear envelope allows for
      the controlled exchange of macromolecules between the two compartments through
      nuclear pores and presents a surface for anchoring and organizing cytoskeletal
      components and chromatin. Although our molecular understanding of the nuclear
      envelope in higher plants is only just beginning, fundamental differences from
      the animal nuclear envelope have already been found. This review provides an
      updated investigation of these differences with respect to nuclear pore
      complexes, targeting of Ran signalling to the nuclear envelope, inner nuclear
      envelope proteins, and the role and fate of the nuclear envelope during mitosis.

PMID- 16804055
TI  - The strawberry gene FaGAST affects plant growth through inhibition of cell
      elongation.
AB  - The strawberry (Fragaria x ananassa) FaGAST gene encodes a small protein with 12
      cysteine residues conserved in the C-terminal region similar to a group of
      proteins identified in other species with diverse assigned functions such as cell
      division, elongation, or elongation arrest. This gene is expressed in the fruit
      receptacle, with two peaks during ripening at the white and the red-ripe stages,
      both coincident with an arrest in the growth pattern. Expression is also high in
      the roots but confined to the cells at the end of the elongation zone. Exogenous
      application of gibberellin increased the transcript level of the FaGAST gene in
      strawberry fruits. Ectopic expression of FaGAST in transgenic Fragaria vesca
      under the control of the CaMV-35S promoter caused both delayed growth of the
      plant and fruits with reduced size. The same growth defect was observed in
      Arabidopsis thaliana plants overexpressing FaGAST. In addition, the transgenic
      plants exhibited late flowering and low sensitivity to exogenous gibberellin.
      Taken together, the expression pattern, the regulation by gibberellin, and the
      transgenic phenotypes point to a role for FaGAST in arresting cell elongation
      during strawberry fruit ripening.

PMID- 16804057
TI  - Interventional strategies to prevent beta-cell apoptosis in islet
      transplantation.
AB  - A substantial proportion of the transplanted islet mass fails to engraft due to
      death by apoptosis, and a number of strategies have been explored to inhibit beta
      cell loss. Inhibition of extrinsic signals of apoptosis (i.e., cFLIP or A20) have
      been explored in experimental islet transplantation but have only shown limited
      impact. Similarly, strategies targeted at intrinsic signal inhibition (i.e., BCL
      2) have not yet provided substantial improvement in islet engraftment. Recently,
      investigation of downstream apoptosis inhibitors that block the final common
      pathway (i.e., X-linked inhibitor of apoptosis protein [XIAP]) have demonstrated
      promise in both human and rodent models of engraftment. In addition, XIAP has
      enhanced long-term murine islet allograft survival. The complexities of both
      intrinsic and extrinsic apoptotic pathway inhibition are discussed in depth.

PMID- 16804056
TI  - The proteomics of plant cell membranes.
AB  - Membrane proteins are involved in many different functions depending on their
      location in the cell. Characterization of the membrane proteome can bring new
      insights to the function of different plant membrane systems and the subcellular
      compartments where the proteins are found. Plant membrane proteomics can also
      provide valuable information about plant-specific biological processes. Despite
      recent advances in the separation and techniques for the analysis of plant
      membrane proteins, characterization of these proteins, especially the hydrophobic
      ones, is still challenging. In this review, plant membrane proteomics data,
      compiled from the literature on Arabidopsis thaliana, are described. In addition,
      initial attempts towards determining the physiological significance of some
      proteins identified from membrane proteomics in rice are also described.

PMID- 16804058
TI  - Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding
      proteins in leptin-deficient mice.
AB  - Fatty acid-binding proteins (FABPs) are cytosolic fatty acid chaperones that play
      a critical role in systemic regulation of lipid and glucose metabolism. In
      animals lacking the adipocyte/macrophage FABP isoforms aP2 and mal1, there is
      strong protection against diet-induced obesity, insulin resistance, type 2
      diabetes, fatty liver disease, and hypercholesterolemic atherosclerosis. On high
      fat diet, FABP-deficient mice also exhibit enhanced muscle AMP-activated kinase
      (AMPK) and reduced liver stearoyl-CoA desaturase-1 (SCD-1) activities. Here, we
      performed a cross between aP2(-/-), mal1(-/-), and leptin-deficient (ob/ob) mice
      to elucidate the role of leptin action on the metabolic phenotype of aP2-mal1
      deficiency. The extent of obesity in the ob/ob-aP2-mal1(-/-) mice was comparable
      with ob/ob mice. However, despite severe obesity, ob/ob-aP2-mal1(-/-) mice
      remained euglycemic and demonstrated improved peripheral insulin sensitivity.
      There was also a striking protection from liver fatty infiltration in the ob/ob
      aP2-mal1(-/-) mice with strong suppression of SCD-1 activity. On the other hand,
      the enhanced muscle AMPK activity in aP2-mal1(-/-) mice was lost in the ob/ob
      background. These results indicated that both decreased body weight and enhanced
      muscle AMPK activity in aP2-mal1(-/-) mice are potentially leptin dependent but
      improved systemic insulin sensitivity and protection from liver fatty
      infiltration are largely unrelated to leptin action and that insulin-sensitizing
      effects of FABP deficiency are, at least in part, independent of its effects on
      total-body adiposity.

PMID- 16804059
TI  - A glucose sensor role for glucokinase in anterior pituitary cells.
AB  - Enzymatic activity of glucokinase was demonstrated, quantitated, and
      characterized kinetically in rat and mouse pituitary extracts using a highly
      specific and sensitive spectrometric assay. A previously proposed hypothesis that
      the glucokinase gene might be expressed in the pituitary corticotrophic cells was
      therefore reexamined using mRNA in situ hybridization and immunohistochemical
      techniques. No evidence was found that corticotrophs are glucokinase positive,
      and the identity of glucokinase-expressing cells remains to be determined. The
      findings do, however, suggest a novel hypothesis that a critical subgroup of
      anterior pituitary cells might function as glucose sensor cells and that direct
      fuel regulation of such cells may modify the classical indirect neuroendocrine
      pathways that are known to control hormone secretion from anterior pituitary
      cells.

PMID- 16804060
TI  - Spontaneous recovery from hyperglycemia by regeneration of pancreatic beta-cells
      in Kir6.2G132S transgenic mice.
AB  - The ATP-sensitive K(+) channel (K(ATP) channel) in pancreatic beta-cells is a
      critical regulator in insulin secretion. We previously reported that transgenic
      mice expressing a dominant-negative form (Kir6.2G132S) of Kir6.2, a subunit of
      the K(ATP) channel, specifically in beta-cells develop severe hyperglycemia in
      adults (8 weeks of age). In this study, we conducted a long-term investigation of
      the phenotype of these transgenic mice. Surprisingly, hyperglycemia was
      spontaneously improved with concomitant improvement of pancreatic insulin content
      in the transgenic mice at >25 weeks of age. Insulin-positive cells and pancreatic
      duodenal homeobox 1 (PDX1)-positive cells both were clearly increased in the
      older compared with the younger transgenic mice. Interestingly, cells labeled
      with the lectin Dolichos biflorus agglutinin (DBA), a potential indicator of
      uncommitted pancreatic epithelial/ductal cells, were detected in the islets of
      the transgenic mice but not in those of wild-type mice. In addition, a subset of
      the DBA-labeled cells was positive for PDX1, insulin, glucagon, somatostatin, or
      pancreatic polypeptide. Moreover, some of the DBA-labeled cells were also
      positive for a proliferating cell marker. These results show that the Kir6.2G132S
      transgenic mouse is a useful model for studying beta-cell regeneration and that
      DBA-labeled cells participate in the process.

PMID- 16804061
TI  - Cystic fibrosis transmembrane conductance regulator deficiency exacerbates islet
      cell dysfunction after beta-cell injury.
AB  - The cause of cystic fibrosis-related diabetes (CFRD) remains unknown, but cystic
      fibrosis transmembrane conductance regulator (CFTR) mutations contribute directly
      to multiple aspects of the cystic fibrosis phenotype. We hypothesized that
      susceptibility to islet dysfunction in cystic fibrosis is determined by the lack
      of functional CFTR. To address this, glycemia was assessed in CFTR null (CFTR(-/
      )), C57BL/6J, and FVB/NJ mice after streptozotocin (STZ)-induced beta-cell
      injury. Fasting blood glucose levels were similar among age-matched non-STZ
      administered animals, but they were significantly higher in CFTR(-/-) mice 4
      weeks after STZ administration (288.4 +/- 97.4, 168.4 +/- 35.9, and 188.0 +/-
      42.3 mg/dl for CFTR(-/-), C57BL/6J, and FVB/NJ, respectively; P < 0.05). After
      intraperitoneal glucose administration, elevated blood glucose levels were also
      observed in STZ-administered CFTR(-/-) mice. STZ reduced islets among all
      strains; however, only CFTR(-/-) mice demonstrated a negative correlation between
      islet number and fasting blood glucose (P = 0.02). To determine whether a second
      alteration associated with cystic fibrosis (i.e., airway inflammation) could
      impact glucose control, animals were challenged with Aspergillus fumigatus. The
      A. fumigatus-sensitized CFTR(-/-) mice demonstrated similar fasting and
      stimulated glucose responses in comparison to nonsensitized animals. These
      studies suggest metabolic derangements in CFRD originate from an islet
      dysfunction inherent to the CFTR(-/-) state.

PMID- 16804062
TI  - Aldose reductase-deficient mice are protected from delayed motor nerve conduction
      velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced
      glutathione, increased superoxide accumulation, and DNA damage.
AB  - The exaggerated flux through polyol pathway during diabetes is thought to be a
      major cause of lesions in the peripheral nerves. Here, we used aldose reductase
      (AR)-deficient (AR(-/-)) and AR inhibitor (ARI)-treated mice to further
      understand the in vivo role of polyol pathway in the pathogenesis of diabetic
      neuropathy. Under normal conditions, there were no obvious differences in the
      innervation patterns between wild-type AR (AR(+/+)) and AR(-/-) mice. Under short
      term diabetic conditions, AR(-/-) mice were protected from the reduction of motor
      and sensory nerve conduction velocities observed in diabetic AR(+/+) mice.
      Sorbitol levels in the sciatic nerves of diabetic AR(+/+) mice were increased
      significantly, whereas sorbitol levels in the diabetic AR(-/-) mice were
      significantly lower than those in diabetic AR(+/+) mice. In addition, signs of
      oxidative stress, such as increased activation of c-Jun NH(2)-terminal kinase
      (JNK), depletion of reduced glutathione, increase of superoxide formation, and
      DNA damage, observed in the sciatic nerves of diabetic AR(+/+) mice were not
      observed in the diabetic AR(-/-) mice, indicating that the diabetic AR(-/-) mice
      were protected from oxidative stress in the sciatic nerve. The diabetic AR(-/-)
      mice also excreted less 8-hydroxy-2'-deoxyguanosine in urine than diabetic
      AR(+/+) mice. The structural abnormalities observed in the sural nerve of
      diabetic AR(+/+) mice were less severe in the diabetic AR(-/-) mice, although it
      was only mildly protected by AR deficiency under short-term diabetic conditions.
      Signs of oxidative stress and functional and structural abnormalities were also
      inhibited by the ARI fidarestat in diabetic AR(+/+) nerves, similar to those in
      diabetic AR(-/-) mice. Taken together, increased polyol pathway flux through AR
      is a major contributing factor in the early signs of diabetic neuropathy,
      possibly through depletion of glutathione, increased superoxide accumulation,
      increased JNK activation, and DNA damage.

PMID- 16804064
TI  - Increased dicarbonyl metabolism in endothelial cells in hyperglycemia induces
      anoikis and impairs angiogenesis by RGD and GFOGER motif modification.
AB  - Chronic vascular disease in diabetes is associated with disruption of
      extracellular matrix (ECM) interactions with adherent endothelial cells,
      compromising cell survival and impairing vasculature structure. Loss of
      functional contact with integrins activates anoikis and impairs angiogenesis. The
      metabolic dysfunction underlying this vascular damage and disruption is unclear.
      Here, we show that increased modification of vascular basement membrane type IV
      collagen by methylglyoxal, a dicarbonyl glycating agent with increased formation
      in hyperglycemia, formed arginine-derived hydroimidazolone residues at hotspot
      modification sites in RGD and GFOGER integrin-binding sites of collagen, causing
      endothelial cell detachment, anoikis, and inhibition of angiogenesis. Endothelial
      cells incubated in model hyperglycemia in vitro and experimental diabetes in vivo
      produced the same modifications of vascular collagen, inducing similar responses.
      Pharmacological scavenging of methylglyoxal prevented anoikis and maintained
      angiogenesis, and inhibition of methylglyoxal metabolism with a cell permeable
      glyoxalase I inhibitor provoked these responses in normoglycemia. Thus, increased
      formation of methylglyoxal and ECM glycation in hyperglycemia impairs endothelial
      cell survival and angiogenesis and likely contributes to similar vascular
      dysfunction in diabetes.

PMID- 16804063
TI  - Comparison of serum high-molecular weight (HMW) adiponectin with total
      adiponectin concentrations in type 2 diabetic patients with coronary artery
      disease using a novel enzyme-linked immunosorbent assay to detect HMW
      adiponectin.
AB  - Adiponectin (Acrp30), an adipocyte-derived protein, exists in serum as a trimer,
      a hexamer, and a high-molecular weight (HMW) form, including 12-18 subunits.
      Because HMW adiponectin may be biologically active, we measured it in serum using
      a novel enzyme-linked immunosorbent assay (ELISA) confirmed by gel filtration
      chromatography that the ELISA detected mainly adiponectin with 12-18 subunits,
      and we compared HMW with total adiponectin concentration in patients with type 2
      diabetes. We next investigated the relationship between serum HMW and coronary
      artery disease (CAD) in 280 consecutive type 2 diabetic patients, including 59
      patients with angiographically confirmed CAD. Total adiponectin was measured in
      serum by a commercially available ELISA. Like serum total adiponectin, HMW
      adiponectin correlated positively with HDL cholesterol and negatively with
      triglyceride, insulin sensitivity, creatinine clearance, and circulating
      inflammatory markers. Total and HMW adiponectin were significantly higher in
      women than in men, as was the HMW-to-total adiponectin ratio. Serum HMW and the
      HMW-to-total adiponectin ratio were significantly lower in men with than without
      CAD (P < 0.05, respectively). In women, the ratio, but neither total nor HMW
      adiponectin, tended to be lower when CAD was present. In conclusion,
      determination of HMW adiponectin, especially relative to total serum adiponectin,
      is useful for evaluating CAD in type 2 diabetic patients.

PMID- 16804065
TI  - Common hepatic nuclear factor-4alpha variants are associated with high serum
      lipid levels and the metabolic syndrome.
AB  - Hepatic nuclear factor-4alpha (HNF-4alpha), a transcription factor involved in
      the regulation of serum lipid and glucose levels, has recently been associated
      with type 2 diabetes. The HNF-4alpha gene (HNF4A) resides on chromosome 20q12
      q13.1, which, in addition to type 2 diabetes, has also previously been linked to
      high triglycerides in Finnish familial combined hyperlipidemia (FCHL) families.
      FCHL, characterized by elevated levels of serum total cholesterol, triglycerides,
      or both, is a common dyslipidemia observed in up to 20% of patients with
      premature coronary heart disease. Considering the clear phenotypic overlap
      between type 2 diabetes and FCHL, both predisposing to high serum triglycerides
      and glucose intolerance, we tested this gene for association in dyslipidemic
      families originating from two distinct populations, Finnish and Mexican, and
      comprising 1,447 subjects. Our data show that common HNF4A variants and
      haplotypes are associated with elevated serum lipid levels and the metabolic
      syndrome (P = 0.008-0.04), as well as with elevated glucose parameters (P = 0.008
      0.03), using family-based association analysis. Importantly, both Finnish and
      Mexican families shared two common lipid-associated HNF4A haplotypes (P = 0.005
      for total cholesterol and 0.006 for triglycerides). In conclusion, we show for
      the first time that common HNF4A variants are associated with high serum lipid
      levels and the metabolic syndrome.

PMID- 16804066
TI  - Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes
      dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout.
AB  - A series of recent studies in humans and the NOD mouse model have highlighted the
      central role that autoimmunity directed against insulin, in particular the
      insulin B chain 9-23 peptide, may play in the pathogenesis of type 1 diabetes.
      Both pathogenic and protective T-cell clones recognizing the B:9-23 peptide have
      been produced. This report describes the successful creation of BDC12-4.1 T-cell
      receptor (TCR) transgenic mice with spontaneous insulitis in F1 mice (FVB x NOD)
      and spontaneous diabetes in NOD.RAG(-/-) (backcross 1 generation). Disease
      progression is heterogeneous and is modified by a series of genetic factors
      including heterozygosity (H-2(g7)/H-2(q)) versus homozygosity for H-2(g7), the
      presence of additional T-/B-cell receptor-rearranged genes (RAG(+) versus RAG(-/
      )), and the insulin 2 gene knockout (the insulin gene expressed in the NOD
      thymus). Despite lymphopenia, 40% of H-2(g7/g7) BDC12-4.1 TCR(+) RAG(-/-) Ins2(-/
      ) mice are diabetic by 10 weeks of age. As few as 13,500 transgenic T-cells from
      a diabetic TCR(+) RAG(-/-) mouse can transfer diabetes to an NOD.scid mouse. The
      current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes
      at NOD backcross 1, bypassing polygenic inhibition of insulitis and
      diabetogenesis.

PMID- 16804067
TI  - Coincident linkage of type 2 diabetes, metabolic syndrome, and measures of
      cardiovascular disease in a genome scan of the diabetes heart study.
AB  - Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in
      type 2 diabetes, but the relationship between CVD and type 2 diabetes is not well
      understood. The Diabetes Heart Study is a study of type 2 diabetes-enriched
      families extensively phenotyped for measures of CVD, type 2 diabetes, and
      metabolic syndrome. A total of 977 Caucasian subjects from 358 pedigrees (575
      type 2 diabetic relative pairs) with at least two individuals with type 2
      diabetes and, where possible, unaffected siblings were included in a genome scan.
      Qualitative traits evaluated in this analysis are with or without the presence of
      coronary calcified plaque (CCP) and with or without carotid calcified plaque
      (CarCP) measured by electrocardiogram-gated helical computed tomography. In
      addition, prevalent CVD was measured using two definitions: CVD1, based on self
      reported history of clinical CVD (393 subjects), and CVD2, defined as CVD1 and/or
      CCP >400 (606 subjects). These discrete traits (type 2 diabetes, metabolic
      syndrome, CVD1, CVD2, CCP, and CarCP) frequently coincide in the same individuals
      with concordance ranging from 42.9 to 99%. Multipoint nonparametric linkage
      analysis revealed evidence for coincident mapping of each trait (type 2 diabetes,
      metabolic syndrome, CVD1, CVD2, CCP, and CarCP) to three different genomic
      regions: a broad region on chromosome 3 (70-160 cM; logarithm of odds [LOD]
      scores ranging between 1.15 and 2.71), chromosome 4q31 (peak LOD 146 cM; LOD
      scores ranging between 0.90 and 2.41), and on chromosome 14p (peak LOD 23 cM; LOD
      scores ranging between 1.43 and 2.31). Ordered subset analysis (OSA) suggests
      that the linked chromosome 3 region consists of at least two separate loci on 3p
      and 3q. In addition, OSA based on lipid measures and other traits identify family
      subsets with significantly stronger evidence of linkage (e.g., CVD2 on chromosome
      3 at 87 cM subsetting on low HDL with an initial LOD of 2.19 is maximized to an
      LOD of 7.04 in a subset of 25% of the families and CVD2 on chromosome 14 at 22 cM
      subsetting on high triglycerides with an initial LOD of 1.99 maximized to an LOD
      of 4.90 in 44% of the families). When subjects are defined as affected by the
      presence of each trait (type 2 diabetes, metabolic syndrome, CVD1, and CCP),
      significant evidence for linkage to the 3p locus is observed with a peak LOD of
      4.13 at 87 cM. While the correlated nature of the traits makes it unclear whether
      these loci represent distinct type 2 diabetes, metabolic syndrome, or CVD loci or
      single loci with pleiotropic effects, the coincident linkage suggests that
      identification of the underlying genes may help clarify the relationship of
      diabetes, metabolic syndrome, and CVD.

PMID- 16804068
TI  - Evaluation of the effect of gain on the meal response of an automated closed-loop
      insulin delivery system.
AB  - A continuous closed-loop insulin delivery system using subcutaneous insulin
      delivery was evaluated in eight diabetic canines. Continuous glucose profiles
      were obtained by extrapolation of blood glucose measurements. Insulin delivery
      rate was calculated, using a model of beta-cell insulin secretion, and delivered
      with a Medtronic MiniMed subcutaneous infusion pump. The model acts like a
      classic proportional-integral-derivative controller, delivering insulin in
      proportion to glucose above target, history of past glucose values, and glucose
      rate of change. For each dog, a proportional gain was set relative to the open
      loop total daily dose (TDD) of insulin. Additional gains based on 0.5 x TDD and
      1.5 x TDD were also evaluated (gain dose response). Control was initiated 4 h
      before the meal with a target of 6.7 mmol/l. At the time of the meal, glucose was
      similar for all three gains (6.0 +/- 0.3, 5.2 +/- 0.3, and 4.9 +/- 0.5 mmol/l for
      0.5 x TDD, TDD, and 1.5 x TDD, respectively; P > 0.05) with near-target values
      restored at the end of experiments (8.2 +/- 0.9, 6.0 +/- 0.6, and 6.0 +/- 0.5,
      respectively). The peak postprandial glucose level decreased significantly with
      increasing gain (12.1 +/- 0.6, 9.6 +/- 1.0, and 8.5 +/- 0.6 mmol/l, respectively;
      P < 0.05). The data demonstrate that closed-loop insulin delivery using the
      subcutaneous site can provide stable glycemic control within a range of gain.

PMID- 16804069
TI  - Effects of age and sex on postprandial glucose metabolism: differences in glucose
      turnover, insulin secretion, insulin action, and hepatic insulin extraction.
AB  - To determine the effects of age and sex on the regulation of postprandial glucose
      metabolism, glucose turnover, insulin secretion, insulin action, and hepatic
      insulin extraction were concurrently measured in 145 healthy elderly (aged 70 +/-
      1 years) and in 58 young (aged 28 +/- 1 years) men and women before and after
      ingestion of a mixed meal containing [1-(13)C]glucose. At the time of meal
      ingestion, [6-(3)H]glucose and [6,6-(2)H(2)]glucose were infused intravenously to
      enable concurrent measurement of the rates of postprandial endogenous glucose
      production (EGP), meal appearance, and glucose disappearance. Fasting and
      postprandial glucose concentrations were higher (P < 0.001) in both elderly women
      and elderly men compared with young individuals of the same sex. The higher
      postprandial glucose concentrations in the elderly than young women were caused
      by higher rates of meal appearance (P < 0.01) and slightly lower (P < 0.05) rates
      of glucose disappearance immediately after eating. In contrast, higher glucose
      concentrations in the elderly than young men were solely due to decreased (P <
      0.001) glucose disappearance. Although postprandial glucose concentrations did
      not differ in elderly women and elderly men, rates of meal appearance and glucose
      disappearance rates both were higher (P < 0.001) in the women. Fasting EGP was
      higher (P < 0.05) in elderly than young subjects of both sexes and in women than
      men regardless of age. On the other hand, postprandial suppression of EGP was
      rapid all groups. Insulin action and secretion were lower (P < 0.001) in the
      elderly than young men but did not differ in the elderly and young women. This
      resulted in lower (P < 0.001) meal disposition indexes in elderly than young men
      but no difference in elderly and young women. Total meal disposition indexes were
      lower (P < 0.05) in elderly men than elderly women, indicating impaired insulin
      secretion, whereas disposition indexes were higher (P < 0.05) in young men than
      young women. Hepatic insulin clearance was greater (P < 0.001) in the elderly
      than young subjects of both sexes but did not differ between men and women
      regardless of age. In contrast, the ability of glucose to facilitate its own
      uptake (glucose effectiveness) was higher (P < 0.001) in women than men but did
      not differ in elderly and young subjects. Thus, age and sex impact on insulin
      secretion, insulin action, hepatic insulin extraction, and glucose effectiveness,
      resulting in substantial differences in the regulation of postprandial glucose
      metabolism in men and women and in elderly and young subjects.

PMID- 16804070
TI  - A choline-deficient diet exacerbates fatty liver but attenuates insulin
      resistance and glucose intolerance in mice fed a high-fat diet.
AB  - Liver fat accumulation is proposed to link obesity and insulin resistance. To
      dissect the role of liver fat in the insulin resistance of diet-induced obesity,
      we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low
      fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during the
      final 4 weeks, diets were either choline deficient or choline supplemented. In
      choline replete animals, high-fat feeding induced weight gain, elevated liver
      triglycerides (171%), hyperinsulinemia, and glucose intolerance. Choline
      deficiency did not affect body or adipose depot weights but amplified liver fat
      accumulation with high-fat diet (281%, P < 0.01). However, choline deficiency
      lowered fasting plasma insulin (from 983 +/- 175 to 433 +/- 36 pmol/l, P < 0.01)
      and improved glucose tolerance on a high-fat diet. In mice on 30% fat diet,
      choline deficiency increased liver mRNA levels of the rate-limiting enzyme in
      phosphatidylcholine synthesis and of enzymes involved in free fatty acid
      esterification, without affecting those of de novo lipogenesis or fatty acid
      oxidation. We conclude that liver fat accumulation per se does not cause insulin
      resistance during high-fat feeding and that choline deficiency may shunt
      potentially toxic free fatty acids toward innocuous storage triglyceride in the
      liver.

PMID- 16804071
TI  - Plasma interleukin-6 levels are independently associated with insulin secretion
      in a cohort of Italian-Caucasian nondiabetic subjects.
AB  - We have investigated the relationships between plasma interleukin-6 (IL-6) levels
      and insulin sensitivity and insulin secretion in a cohort of Italian-Caucasian
      glucose-tolerant subjects. Insulin sensitivity was assessed by euglycemic
      hyperinsulinemic clamp, and first-phase insulin secretion was measured by
      intravenous glucose tolerance test. Fasting plasma IL-6 concentration was
      negatively correlated with the rate of insulin-stimulated glucose disposal (M) (P
      = 0.001). The correlation remained statistically significant, while attenuated,
      after adjusting for sex, age, and BMI (P < 0.03); after an additional adjustment
      for free fatty acids (FFAs), a further attenuation was observed, but statistical
      significance was maintained (P < 0.044). Fasting plasma IL-6 concentration was
      positively correlated with first-phase insulin secretion assessed as acute
      insulin response (AIR) (P = 0.001). The correlation remained significant after
      adjusting for sex, age, and BMI (P = 0.003). To estimate the independent
      contribution of plasma IL-6 levels to AIR, we carried out forward stepwise linear
      regression analysis in a model that included sex, age, BMI, waist-to-hip ratio,
      FFAs, and insulin-stimulated glucose disposal. Only insulin sensitivity and
      plasma IL-6 concentration were independently associated with AIR, accounting,
      respectively, for 19.0 and 5.2% of its variation. These data indicate that IL-6
      is associated in a reciprocal manner with the two pathophysiological components
      of type 2 diabetes, i.e., insulin resistance and insulin secretion.

PMID- 16804072
TI  - Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric
      surgery.
AB  - Currently, there are no data in the literature regarding the pathophysiological
      mechanisms involved in the rapid resolution of type 2 diabetes after bariatric
      surgery, which was reported as an additional benefit of the surgical treatment
      for morbid obesity. With this question in mind, insulin sensitivity, using
      euglycemic-hyperinsulinemic clamp, and insulin secretion, by the C-peptide
      deconvolution method after an oral glucose load, together with the circulating
      levels of intestinal incretins and adipocytokines, have been studied in 10
      diabetic morbidly obese subjects before and shortly after biliopancreatic
      diversion (BPD) to avoid the weight loss interference. Diabetes disappeared 1
      week after BPD, while insulin sensitivity (32.96 +/- 4.3 to 65.73 +/- 3.22 mumol
      . kg fat-free mass(-1) . min(-1) at 1 week and to 64.73 +/- 3.42 mumol . kg fat
      free mass(-1) . min(-1) at 4 weeks; P < 0.0001) was fully normalized. Fasting
      insulin secretion rate (148.16 +/- 20.07 to 70.0.2 +/- 8.14 and 83.24 +/- 8.28
      pmol/min per m(2); P < 0.01) and total insulin output (43.76 +/- 4.07 to 25.48 +/
      1.69 and 30.50 +/- 4.71 nmol/m(2); P < 0.05) dramatically decreased, while a
      significant improvement in beta-cell glucose sensitivity was observed. Both
      fasting and glucose-stimulated gastrointestinal polypeptide (13.40 +/- 1.99 to
      6.58 +/- 1.72 pmol/l at 1 week and 5.83 +/- 0.80 pmol/l at 4 weeks) significantly
      (P < 0.001) decreased, while glucagon-like peptide 1 significantly increased
      (1.75 +/- 0.16 to 3.42 +/- 0.41 pmol/l at 1 week and 3.62 +/- 0.21 pmol/l at 4
      weeks; P < 0.001). BPD determines a prompt reversibility of type 2 diabetes by
      normalizing peripheral insulin sensitivity and enhancing beta-cell sensitivity to
      glucose, these changes occurring very early after the operation. This operation
      may affect the enteroinsular axis function by diverting nutrients away from the
      proximal gastrointestinal tract and by delivering incompletely digested nutrients
      to the ileum.

PMID- 16804073
TI  - Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin
      and sterol regulatory element-binding protein-1c.
AB  - Stearoyl-CoA desaturase (SCD)1 catalyzes the rate-limiting reaction of
      monounsaturated fatty acid (MUFA) synthesis and plays an important role in the
      development of obesity. SCD1 is suppressed by leptin but induced by insulin. We
      have used animal models to dissect the effects of these hormones on SCD1. In the
      first model, leptin-deficient ob/ob mice were treated with either leptin alone or
      with both leptin and insulin to prevent the leptin-mediated fall in insulin. In
      the second model, mice with a liver-specific knockout of the insulin receptor
      (LIRKO) and their littermate controls (LOXs) were treated with leptin. As
      expected, leptin decreased SCD1 transcript, protein, and activity by >60% in
      ob/ob and LOX mice. However, the effects of leptin were not diminished by the
      continued presence of hyperinsulinemia in ob/ob mice treated with both leptin and
      insulin or the absence of insulin signaling in LIRKO mice. Furthermore, genetic
      knockout of sterol regulatory element-binding protein (SREBP)-1c, the lipogenic
      transcription factor that mediates the effects of insulin on SCD1, also had no
      effect on the ability of leptin to decrease either SCD1 transcript or activity.
      Thus, the effect of leptin on SCD1 in liver is independent of insulin and SREBP
      1c, and leptin, rather than insulin, is the major regulator of hepatic MUFA
      synthesis in obesity-linked diabetes.

PMID- 16804074
TI  - Targeting foxo1 in mice using antisense oligonucleotide improves hepatic and
      peripheral insulin action.
AB  - Fasting hyperglycemia, a prominent finding in diabetes, is primarily due to
      increased gluconeogenesis. The transcription factor Foxo1 links insulin signaling
      to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and
      provides a possible therapeutic target in insulin-resistant states. Synthetic,
      optimized antisense oligonucleotides (ASOs) specifically inhibit Foxo1
      expression. Here we show the effect of such therapy on insulin resistance in mice
      with diet-induced obesity (DIO). Reducing Foxo1 mRNA expression with ASO therapy
      in mouse hepatocytes decreased levels of Foxo1 protein and mRNA expression of
      PEPCK by 48 +/- 4% and G6Pase by 64 +/- 3%. In mice with DIO and insulin
      resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate
      of basal endogenous glucose production. In addition, Foxo1 ASO therapy lowered
      both hepatic triglyceride and diacylglycerol content and improved hepatic insulin
      sensitivity. Foxo1 ASO also improved adipocyte insulin action. At a tissue
      specific level, this manifested as improved insulin-mediated 2-deoxyglucose
      uptake and suppression of lipolysis. On a whole-body level, the result was
      improved glucose tolerance after an intraperitoneal glucose load and increased
      insulin-stimulated whole-body glucose disposal during a hyperinsulinemic
      euglycemic clamp. In conclusion, Foxo1 ASO therapy improved both hepatic insulin
      and peripheral insulin action. Foxo1 is a potential therapeutic target for
      improving insulin resistance.

PMID- 16804075
TI  - AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK
      catalytic and regulatory subunits.
AB  - AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates
      glucose transport mediated by cellular stress or pharmacological agonists such as
      5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR). AS160, a Rab
      GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose
      uptake. We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160
      phosphorylation by insulin-independent mechanisms in isolated skeletal muscle.
      Recombinant AMPK heterotrimeric complexes (alpha1beta1gamma1 and
      alpha2beta2gamma1) phosphorylate AS160 in a cell-free assay. In mice deficient in
      AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and
      gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted,
      highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR
      stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated
      AS160 phosphorylation was also impaired in alpha2 AMPK KO and KD but not gamma3
      AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.

PMID- 16804076
TI  - Serum- and glucocorticoid-inducible kinase 1 mediates salt sensitivity of glucose
      tolerance.
AB  - Excess salt intake decreases peripheral glucose uptake, thus impairing glucose
      tolerance. Stimulation of cellular glucose uptake involves phosphatidylinositide
      3-kinase (PI-3K)-dependent activation of protein kinase B/Akt. A further kinase
      downstream of PI-3K is serum- and glucocorticoid-inducible kinase (SGK)1, which
      is upregulated by mineralocorticoids and, thus, downregulated by salt intake. To
      explore the role of SGK1 in salt-dependent glucose uptake, SGK1 knockout mice
      (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)) were allowed free access
      to either tap water (control) or 1% saline (high salt). According to Western
      blotting, high salt decreased and deoxycorticosterone acetate (DOCA; 35 mg/kg
      body wt) increased SGK1 protein abundance in skeletal muscle and fat tissue of
      sgk1(+/+) mice. Intraperitoneal injection of glucose (3 g/kg body wt) into
      sgk1(+/+) mice transiently increased plasma glucose concentration approaching
      significantly higher values ([glucose]p,max) in high salt (281 +/- 39 mg/dl) than
      in control (164 +/- 23 mg/dl) animals. DOCA did not significantly modify
      [glucose]p,max in control sgk1(+/+) mice but significantly decreased
      [glucose]p,max in high-salt sgk1(+/+) mice, an effect reversed by spironolactone
      (50 mg/kg body wt). [Glucose]p,max was in sgk1(-/-) mice insensitive to high salt
      and significantly higher than in control sgk1(+/+) mice. Uptake of 2-deoxy-d-[1,2
      (3)H]glucose into skeletal muscle and fat tissue was significantly smaller in
      sgk1(-/-) mice than in sgk1(+/+) mice and decreased by high salt in sgk1(+/+)
      mice. Transfection of HEK-293 cells with active (S422D)SGK1, but not inactive
      (K127N)SGK, stimulated phloretin-sensitive glucose uptake. In conclusion, high
      salt decreases SGK1-dependent cellular glucose uptake. SGK1 thus participates in
      the link between salt intake and glucose tolerance.

PMID- 16804077
TI  - Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR,
      and contraction in mouse skeletal muscle.
AB  - Insulin and contraction increase GLUT4 translocation in skeletal muscle via
      distinct signaling mechanisms. Akt substrate of 160 kDa (AS160) mediates insulin
      stimulated GLUT4 translocation in L6 myotubes, presumably through activation of
      Akt. Using in vivo, in vitro, and in situ methods, insulin, contraction, and the
      AMP-activated protein kinase (AMPK) activator AICAR all increased AS160
      phosphorylation in mouse skeletal muscle. Insulin-stimulated AS160
      phosphorylation was fully blunted by wortmannin in vitro and in Akt2 knockout
      (KO) mice in vivo. In contrast, contraction-stimulated AS160 phosphorylation was
      only partially decreased by wortmannin and unaffected in Akt2 KO mice, suggesting
      additional regulatory mechanisms. To determine if AMPK mediates AS160 signaling,
      we used AMPK alpha2-inactive (alpha2i) transgenic mice. AICAR-stimulated AS160
      phosphorylation was fully inhibited, whereas contraction-stimulated AS160
      phosphorylation was partially reduced in the AMPK alpha2i transgenic mice.
      Combined AMPK alpha2 and Akt inhibition by wortmannin treatment of AMPK alpha2
      transgenic mice did not fully ablate contraction-stimulated AS160
      phosphorylation. Maximal insulin, together with either AICAR or contraction,
      increased AS160 phosphorylation in an additive manner. In conclusion, AS160 may
      be a point of convergence linking insulin, contraction, and AICAR signaling.
      While Akt and AMPK alpha2 activities are essential for AS160 phosphorylation by
      insulin and AICAR, respectively, neither kinase is indispensable for the entire
      effects of contraction on AS160 phosphorylation.

PMID- 16804078
TI  - The role of Ca2+ influx for insulin-mediated glucose uptake in skeletal muscle.
AB  - The involvement of Ca(2+) in insulin-mediated glucose uptake is uncertain. We
      measured Ca(2+) influx (as Mn(2+) quenching or Ba(2+) influx) and 2-deoxyglucose
      (2-DG) uptake in single muscle fibers isolated from limbs of adult mice; 2-DG
      uptake was also measured in isolated whole muscles. Exposure to insulin increased
      the Ca(2+) influx in single muscle cells. Ca(2+) influx in the presence of
      insulin was decreased by 2-aminoethoxydiphenyl borate (2-APB) and increased by
      the membrane-permeable diacylglycerol analog 1-oleyl-2-acetyl-sn-glycerol (OAG),
      agents frequently used to block and activate, respectively, nonselective cation
      channels. Maneuvers that decreased Ca(2+) influx in the presence of insulin also
      decreased 2-DG uptake, whereas increased Ca(2+) influx was associated with
      increased insulin-mediated glucose uptake in isolated single cells and whole
      muscles from both normal and insulin-resistant obese ob/ob mice. 2-APB and OAG
      affected neither basal nor hypoxia- or contraction-mediated 2-DG uptake. 2-APB
      did not inhibit the insulin-mediated activation of protein kinase B or
      extracellular signal-related kinase 1/2 in whole muscles. In conclusion,
      alterations in Ca(2+) influx specifically modulate insulin-mediated glucose
      uptake in both normal and insulin-resistant skeletal muscle. Moreover, the
      present results indicate that Ca(2+) acts late in the insulin signaling pathway,
      for instance, in the GLUT4 translocation to the plasma membrane.

PMID- 16804079
TI  - Mitochondrial reactive oxygen species are required for hypothalamic glucose
      sensing.
AB  - The physiological signaling mechanisms that link glucose sensing to the
      electrical activity in metabolism-regulating hypothalamus are still
      controversial. Although ATP production was considered the main metabolic signal,
      recent studies show that the glucose-stimulated signaling in neurons is not
      totally dependent on this production. Here, we examined whether mitochondrial
      reactive oxygen species (mROS), which are physiologically generated depending on
      glucose metabolism, may act as physiological sensors to monitor the glucose
      sensing response. Transient increase from 5 to 20 mmol/l glucose stimulates
      reactive oxygen species (ROS) generation on hypothalamic slices ex vivo, which is
      reversed by adding antioxidants, suggesting that hypothalamic cells generate ROS
      to rapidly increase glucose level. Furthermore, in vivo, data demonstrate that
      both the glucose-induced increased neuronal activity in arcuate nucleus and the
      subsequent nervous-mediated insulin release might be mimicked by the
      mitochondrial complex blockers antimycin and rotenone, which generate mROS.
      Adding antioxidants such as trolox and catalase or the uncoupler carbonyl cyanide
      m-chlorophenylhydrazone in order to lower mROS during glucose stimulation
      completely reverses both parameters. In conclusion, the results presented here
      clearly show that the brain glucose-sensing mechanism involved mROS signaling. We
      propose that this mROS production plays a key role in brain metabolic signaling.

PMID- 16804080
TI  - Identification of a novel member of the carboxylesterase family that hydrolyzes
      triacylglycerol: a potential role in adipocyte lipolysis.
AB  - Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty
      acids from adipose tissue, are not fully understood. A database search for
      enzymes with alpha/beta hydrolase folds, the GXSXG motif for serine esterase and
      the His-Gly dipeptide motif, has provided a previously unannotated gene that is
      induced during 3T3-L1 adipocytic differentiation. Because of its remarkable
      structural resemblance to triacylglycerol hydrolase (TGH) with 70.4% identity, we
      have tentatively designated this enzyme as TGH-2 and the original TGH as TGH-1.
      TGH-2 is also similar to TGH-1 in terms of tissue distribution, subcellular
      localization, substrate specificity, and regulation. Both enzymes are
      predominantly expressed in liver, adipose tissue, and kidney. In adipocytes, they
      are localized in microsome and fatcake. Both enzymes hydrolyzed p-nitophenyl
      butyrate, triolein, and monoolein but not diolein, cholesteryl oleate, or
      phospholipids; hydrolysis of short-chain fatty acid ester was 30,000-fold more
      efficient than that of long-chain fatty acid triacylglycerol. Fasting increased
      the expression of both genes in white adipose tissue, whereas refeeding
      suppressed their expression. RNA silencing of TGH-2 reduced isoproterenol
      stimulated glycerol release by 10% in 3T3-L1 adipocytes, while its overexpression
      increased the glycerol release by 20%. Thus, TGH-2 may make a contribution to
      adipocyte lipolysis during period of increased energy demand.

PMID- 16804081
TI  - Deficiency in NOD antigen-presenting cell function may be responsible for
      suboptimal CD4+CD25+ T-cell-mediated regulation and type 1 diabetes development
      in NOD mice.
AB  - Various defects in antigen-presenting cells (APCs) and T-cells, including
      regulatory cells, have been associated with type 1 diabetes development in NOD
      mice. CD4(+)CD25(+) regulatory cells play a crucial role in controlling various
      autoimmune diseases, and a deficiency in their number or function could be
      involved in disease development. The current study shows that NOD mice had fewer
      CD4(+)CD25(+) regulatory cells, which expressed normal levels of glucocorticoid
      induced tumor necrosis factor receptor and cytotoxic T-lymphocyte-associated
      antigen-4. We have also found that NOD CD4(+)CD25(+) cells regulate poorly in
      vitro after stimulation with anti-CD3 and NOD APCs in comparison with B6
      CD4(+)CD25(+) cells stimulated with B6 APCs. Surprisingly, stimulation of NOD
      CD4(+)CD25(+) cells with B6 APCs restored regulation, whereas with the reciprocal
      combination, NOD APCs failed to activate B6 CD4(+)CD25(+) cells properly.
      Interestingly, APCs from disease-free (>30 weeks of age), but not diabetic, NOD
      mice were able to activate CD4(+)CD25(+) regulatory function in vitro and
      apparently in vivo because only spleens of disease-free NOD mice contained potent
      CD4(+)CD25(+) regulatory cells that prevented disease development when
      transferred into young NOD recipients. These data suggest that the failure of NOD
      APCs to activate CD4(+)CD25(+) regulatory cells may play an important role in
      controlling type 1 diabetes development in NOD mice.

PMID- 16804082
TI  - Beta-cell deficit due to increased apoptosis in the human islet amyloid
      polypeptide transgenic (HIP) rat recapitulates the metabolic defects present in
      type 2 diabetes.
AB  - Type 2 diabetes is characterized by defects in insulin secretion and action and
      is preceded by impaired fasting glucose (IFG). The islet anatomy in IFG and type
      2 diabetes reveals an approximately 50 and 65% deficit in beta-cell mass, with
      increased beta-cell apoptosis and islet amyloid derived from islet amyloid
      polypeptide (IAPP). Defects in insulin action include both hepatic and
      extrahepatic insulin resistance. The relationship between changes in beta-cell
      mass, beta-cell function, and insulin action leading to type 2 diabetes are
      unresolved, in part because it is not possible to measure beta-cell mass in vivo,
      and most available animal models do not recapitulate the islet pathology in type
      2 diabetes. We evaluated the HIP rat, a human IAPP transgenic rat model that
      develops islet pathology comparable to humans with type 2 diabetes, at age 2
      months (nondiabetic), 5 months (with IFG), and 10 months (with diabetes) to
      prospectively examine the relationship between changes in islet morphology versus
      insulin secretion and action. We report that increased beta-cell apoptosis and
      impaired first-phase insulin secretion precede the development of IFG, which
      coincides with an approximately 50% defect in beta-cell mass and onset of hepatic
      insulin resistance. Diabetes was characterized by approximately 70% deficit in
      beta-cell mass, progressive hepatic and extrahepatic insulin resistance, and
      hyperglucagonemia. We conclude that IAPP-induced beta-cell apoptosis causes
      defects in insulin secretion and beta-cell mass that lead first to hepatic
      insulin resistance and IFG and then to extrahepatic insulin resistance,
      hyperglucagonemia, and diabetes. We conclude that a specific beta-cell defect can
      recapitulate the metabolic phenotype of type 2 diabetes and note that insulin
      resistance in type 2 diabetes may at least in part be secondary to beta-cell
      failure.

PMID- 16804083
TI  - Mesangial cell hypertrophy by high glucose is mediated by downregulation of the
      tumor suppressor PTEN.
AB  - Diabetic nephropathy is characterized early in its course by glomerular
      hypertrophy and, importantly, mesangial hypertrophy, which correlate with
      eventual glomerulosclerosis. The mechanism of hypertrophy, however, is not known.
      Gene disruption of the tumor suppressor PTEN, a negative regulator of the
      phosphatidylinositol 3-kinase/Akt pathway, in fruit flies and mice demonstrated
      its role in size control in a cell-specific manner. Here, we investigated the
      mechanism of mesangial hypertrophy in response to high extracellular glucose. We
      link early renal hypertrophy with significant reduction in PTEN expression in the
      streptozotocin-induced diabetic kidney cortex and glomeruli, concomitant with
      activation of Akt. Similarly, exposure of mesangial cells to high concentrations
      of glucose also decreased PTEN expression and its phosphatase activity, resulting
      in increased Akt activity. Expression of PTEN inhibited high-glucose-induced
      mesangial cell hypertrophy, and expression of dominant-negative PTEN was
      sufficient to induce hypertrophy. In diabetic nephropathy, the hypertrophic
      effect of hyperglycemia is thought to be mediated by transforming growth factor
      beta (TGF-beta). TGF-beta significantly reduced PTEN expression in mesangial
      cells, with a reduction in its phosphatase activity and an increase in Akt
      activation. PTEN and dominant-negative Akt attenuated TGF-beta-induced
      hypertrophy of mesangial cells. Finally, we show that inhibition of TGF-beta
      signal transduction blocks the effect of high glucose on PTEN downregulation.
      These data identify a novel mechanism placing PTEN as a key regulator of diabetic
      mesangial hypertrophy involving TGF-beta signaling.

PMID- 16804084
TI  - The relationship between plasma osteoprotegerin and endothelium-dependent
      arterial dilation in type 2 diabetes.
AB  - Osteoprotegerin is a recently identified inhibitor of bone resorption. Recent
      studies indicate that osteoprotegerin also acts as an important regulatory
      molecule in the vasculature. The purpose of this study was to investigate the
      relationship between plasma osteoprotegerin levels and endothelium-dependent
      arterial dilation in type 2 diabetic patients. The study subjects included 40
      newly diagnosed type 2 diabetic patients and 46 healthy subjects. All patients
      were given insulin therapy for 6 months. Plasma osteoprotegerin concentration was
      measured in duplicate by a sandwich enzyme-linked immunosorbent assay method, and
      high-resolution ultrasound was used to measure brachial artery diameter at rest,
      after reactive hyperemia, and after sublingual glyceryltrinitrate. The plasma
      osteoprotegerin level in patients before treatment was 3.36 +/- 0.32 ng/l, which
      was significantly higher than that in control subjects (2.38 +/- 0.25 ng/l, P <
      0.001). After 6 months of treatment, osteoprotegerin levels decreased markedly
      (2.83 +/- 0.34 ng/l, P < 0.001). Flow-mediated endothelium-dependent arterial
      dilation in patients before treatment was 3.21 +/- 0.52%, which was significantly
      lower than that in control subjects (4.46 +/- 0.56%, P < 0.01), and it improved
      markedly after 6 months of treatment (4.03 +/- 0.49%, P < 0.01). In multivariate
      analysis, osteoprotegerin was significantly associated with endothelium-dependent
      arterial dilation, fasting blood glucose (FBG), HbA(1c) (A1C), and ultrasensitive
      C-reactive protein (CRP) at baseline (P < 0.01). The absolute changes in
      osteoprotegerin showed significant correlation with changes in endothelium
      dependent arterial dilation, FBG, A1C, and CRP in diabetic patients during the
      course of treatment (P < 0.01). This study shows that plasma osteoprotegerin
      levels are elevated in newly diagnosed diabetic patients and are significantly
      associated with endothelial function.

PMID- 16804085
TI  - ACE and ACE2 activity in diabetic mice.
AB  - ACE-related carboxypeptidase (ACE2) may counterbalance the angiotensin (ANG) II
      promoting effects of ACE in tissues where both enzymes are found. Alterations in
      renal ACE and ACE2 expression have been described in experimental models of
      diabetes, but ACE2 activity was not assessed in previous studies. We developed a
      microplate-based fluorometric method for the concurrent determination of ACE and
      ACE2 activity in tissue samples. Enzymatic activity (relative fluorescence unit
      [RFU] . microg protein(-1) . h(-1)) was examined in ACE and ACE2 knockout mice
      and in two rodent models of diabetes, the db/db and streptozotocin (STZ)-induced
      diabetic mice. In kidney cortex, preparations consisting mainly of proximal
      tubules and cortical collecting tubules, ACE2 activity had a strong positive
      correlation with ACE2 protein expression (90-kDa band) in both knockout models
      and their respective wild-type littermates (r = 0.94, P < 0.01). ACE activity,
      likewise, had a strong positive correlation with renal cortex ACE protein
      expression (170-kDa band) (r = 0.838, P < 0.005). In renal cortex, ACE2 activity
      was increased in both models of diabetes (46.7 +/- 4.4 vs. 22.0 +/- 4.7 in db/db
      and db/m, respectively, P < 0.01, and 22.1 +/- 2.8 vs. 13.1 +/- 1.5 in STZ
      induced diabetic versus untreated mice, respectively, P < 0.05). ACE2 mRNA levels
      in renal cortex from db/db and STZ-induced diabetic mice, by contrast, were not
      significantly different from their respective controls. In cardiac tissue, ACE2
      activity was lower than in renal cortex, and there were no significant
      differences between diabetic and control mice (db/db 2.03 +/- 0.23 vs. db/m 1.85
      +/- 0.10; STZ-induced diabetic 0.42 +/- 0.04 vs. untreated 0.52 +/- 0.07 mice).
      ACE2 activity in renal cortex correlated positively with ACE2 protein in db/db
      and db/m mice (r = 0.666, P < 0.005) as well as in STZ-induced diabetic and
      control mice (r = 0.621, P < 0.05) but not with ACE2 mRNA (r = -0.468 and r = 
      0.522, respectively). We conclude that in renal cortex from diabetic mice, ACE2
      expression is increased at the posttranscriptional level. The availability of an
      assay for concurrent measurement of ACE and ACE2 activity should be helpful in
      the evaluation of kidney-specific alterations in the balance of these two
      carboxypeptidases, which are involved in the control of local ANG II formation
      and degradation.

PMID- 16804086
TI  - Common variants of the endothelial nitric oxide synthase gene and the risk of
      coronary heart disease among U.S. diabetic men.
AB  - Endothelial nitric oxide synthase (eNOS) gene represents a promising candidate
      gene for coronary heart disease (CHD) because of its impact on eNOS activity. We
      systematically examined the associations of eight variants of the eNOS gene (two
      potentially functional variants [-786T>C and Glu298Asp] and six tagging single
      nucleotide polymorphisms) with CHD risk in a large cohort of diabetic patients.
      Among 861 diabetic men (>97% Caucasian) from the Health Professionals Follow-Up
      Study, 220 developed CHD, and 641 men without cardiovascular disease were used as
      control subjects. Genotype distributions of -786T>C and Glu298Asp polymorphisms
      were not significantly different between case and control subjects. CHD risk was
      significantly higher among men with the variant allele at the rs1541861 locus
      (intron 8 A/C) than men without it (adjusted odds ratio 1.5 [95% confidence
      interval 1.1-2.1]). Moreover, among control subjects, plasma soluble vascular
      cell adhesion molecule concentrations were significantly higher among carriers of
      this allele (P 0.019) and carriers of the variant allele of the -786T>C (P
      0.010), or the Glu298Asp polymorphism (P 0.002), compared with noncarriers. In
      conclusion, our data suggested that -786T>C, Glu298Asp, and an intron 8
      polymorphism of the eNOS gene are potentially involved in the atherogenic pathway
      among U.S. diabetic men.

PMID- 16804087
TI  - Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser
      substitution of PGC-1A and the Pro12Ala substitution of PPARG2 predict the
      conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM
      trial.
AB  - Peroxisome proliferator-activated receptor (PPAR)-delta regulates fatty acid
      oxidation and improves insulin sensitivity. We screened six single nucleotide
      polymorphisms (SNPs) of the PPAR-delta gene (PPARD) for an association with the
      conversion from impaired glucose tolerance (IGT) to type 2 diabetes in 769
      subjects participating in the STOP-NIDDM trial. A 2.7-fold increase in the risk
      of diabetes was observed in female carriers of the C allele of rs6902123 (95% CI
      1.44-5.30; adjusted P = 0.002). In the placebo group, subjects possessing both
      the 482Ser allele of the PPAR-gamma coactivator-1alpha gene (PGC-1A) and the rare
      allele of two SNPs of PPARD (rs6902123 and rs3734254) had up to 2.5-fold
      increased risk for diabetes. Furthermore, women carrying the C allele of
      rs6902123 of PPARD and the Pro12Pro genotype of the PPAR-gamma2 gene (PPARG2) had
      a 3.9-fold (95% CI 1.79-8.63; P = 0.001)-higher risk for diabetes than women with
      protective genotypes. Expression levels of PPAR-delta in subcutaneous adipose
      tissue of 87 offspring of Finnish patients with type 2 diabetes did not differ
      among the genotype groups of SNPs of PPARD. We conclude that SNPs in PPARD modify
      the conversion from IGT to type 2 diabetes, particularly in combination with the
      SNPs of PGC-1A and PPARG2.

PMID- 16804088
TI  - Deletion of nicotinamide nucleotide transhydrogenase: a new quantitive trait
      locus accounting for glucose intolerance in C57BL/6J mice.
AB  - The C57BL/6J mouse displays glucose intolerance and reduced insulin secretion.
      The genetic locus underlying this phenotype was mapped to nicotinamide nucleotide
      transhydrogenase (Nnt) on mouse chromosome 13, a nuclear-encoded mitochondrial
      protein involved in beta-cell mitochondrial metabolism. C57BL/6J mice have a
      naturally occurring in-frame five-exon deletion in Nnt that removes exons 7-11.
      This results in a complete absence of Nnt protein in these mice. We show that
      transgenic expression of the entire Nnt gene in C57BL/6J mice rescues their
      impaired insulin secretion and glucose-intolerant phenotype. This study provides
      direct evidence that Nnt deficiency results in defective insulin secretion and
      inappropriate glucose homeostasis in male C57BL/6J mice.

PMID- 16804089
TI  - Working conditions in international seafaring.
AB  - BACKGROUND: Seafaring is a global profession and seafarers have their second home
      on board and live there for several months at a time. AIM: To assess self-rated
      health status and the main characteristics of seafarers' working conditions.
      METHODS: Questionnaire study concerning the most recent tour of duty. RESULTS: A
      total of 6,461 seafarers in 11 countries responded. In general, the seafarers'
      self-rated health was good, but it declined significantly with age. Seafarers
      from South-East Asian countries spent longer time periods at sea, and had lower
      numbers of officers and older seafarers than found among seafarers from western
      countries. Most seafarers worked every day of the week, and on average for 67-70
      h a week during periods of 2.5-8.5 months at sea. CONCLUSIONS: Seafarers' self
      rated health was generally good but varied significantly by country. Working
      conditions also differed by country but did not reflect working conditions in
      general. Further studies are necessary to describe more closely the influence of
      work schedules on the health and social life of seafarers.

PMID- 16804090
TI  - Quest for arthritis-causative genetic factors in the rat.
AB  - Experimental rat models of arthritis are extensively studied with a view to
      understand the genetic underpinnings of rheumatoid arthritis (RA). Genome scans
      using these models have led to the detection of arthritis regulatory quantitative
      trait loci (QTLs) on all but three chromosomes of the rat. Whereas some of the
      QTLs are model specific, others overlap between models. Some arthritis
      susceptibility and/or severity QTLs identified by genetic linkage analyses are
      corroborated by substitution mapping using congenic strains, whereas others are
      not. In these cases, testing alternate arthritis models proved to be useful to
      identify QTL effects. Nevertheless, development and testing of congenic
      substrains containing progressively shorter introgressed regions have not only
      fine mapped the location of the arthritis QTLs but also resulted in the
      identification of multiple QTLs within several originally identified individual
      QTL. Most of these studies progressed rapidly since 2001, when the rat genome
      sequence was published. Proof of principle for substitution mapping as a
      successful method for QTL gene discovery is provided by the positional cloning of
      Ncf1 as one of the arthritis QTLs in rats. This finding is encouraging for
      similar sustained dissection of all the other arthritis QTLs mapped in the rat.
      Identification of rat arthritis QTLs is expected to pave the way for discovery of
      yet-unidentified arthritis-causative genetic elements and/or pathways for RA in
      humans and potential development of targeted therapeutics. This review catalogs
      some of the recent advances made in QTL discovery projects of experimentally
      induced rat models of arthritis.

PMID- 16804091
TI  - Combined behavioral and c-Fos studies elucidate the vital role of sodium for odor
      detection.
AB  - Salt, known as taste quality, is generally neglected in olfaction, although the
      olfactory sensory neurons stretch into the salty nasal mucus covering the
      olfactory epithelium (OE). Using a psychophysical approach, we directly and
      functionally demonstrate in the awake rat for a variety of structurally diverse
      odorants that sodium is a critical factor for olfactory perception and
      sensitivity, both very important components of mammalian communication and sexual
      behavior. Bathing the olfactory mucus with an iso-osmotic sodium-free buffer
      solution results in severe deficits in odorant detection. However, sensitivity
      returns fully within a few hours, indicating continuous mucus production. In the
      presence of sodium in the mucus covering the OE, all odorants induce odorant
      specific c-Fos expression in the olfactory bulb. Yet, if sodium is absent in the
      mucus, no c-Fos expression is induced as demonstrated for n-octanal. Our
      noninvasive approach to induce anosmia in mammals here presented--which is fully
      reversible within hours--opens new possibilities to study the functions of
      olfactory communication in awake animals.

PMID- 16804092
TI  - A naphthoquinone derivative, shikonin, has insulin-like actions by inhibiting
      both phosphatase and tensin homolog deleted on chromosome 10 and tyrosine
      phosphatases.
AB  - The 1,4-naphthoquinone derivative, shikonin, has been shown to increase glucose
      uptake by adipocytes and myocytes with minor effects on protein tyrosine
      phosphorylation in the cells (Biochem Biophys Res Commun 292:642-651, 2002). The
      present study was performed to examine the mechanism of this action of shikonin.
      Shikonin inhibited the phosphatidylinositol 3,4,5-triphosphate (PtdIns-3,4,5-P3)
      phosphatase activity of recombinant phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) with an IC50 value of 2.7 microM. Shikonin induced marked
      accumulation of PtdIns-3,4,5-P3 and activation of protein kinase B (PKB) in
      Chinese hamster ovary cells expressing insulin receptors. In addition to its
      effect on PTEN, shikonin was found to inhibit several protein phosphatases in
      cell-free systems. Its effect on tyrosine phosphorylation in intact cells was far
      weaker than that of pervanadate, a widely used tyrosine phosphatase inhibitor,
      despite the observation that the effect of shikonin on PKB was more potent than
      that of pervanadate. These results suggested that the inhibition of PTEN provides
      a clue to its potent insulin-like actions. We also found that naphthoquinones,
      including 1,2-naphthoquinone, inhibit PTEN in the cell-free system, which
      suggested that the effect on PTEN (and thus the effect on phosphatidylinositol 3
      kinase signaling) should be taken into account when examining the pharmacological
      actions of naphthoquinone derivatives.

PMID- 16804093
TI  - Distinct roles for protein kinase C isoforms in regulating platelet purinergic
      receptor function.
AB  - ADP is a critical regulator of platelet activation, mediating its actions through
      two G protein-coupled receptors (GPCRs), P2Y1 and P2Y12. We have shown previously
      that the receptors are functionally desensitized, in a homologous manner, by
      distinct kinase-dependent mechanisms in which P2Y1 is regulated by protein kinase
      C (PKC) and P2Y12 by G protein-coupled receptor kinases. In this study, we
      addressed whether different PKC isoforms play different roles in regulating the
      trafficking and activity of these two GPCRs. Expression of PKCalpha and PKCdelta
      dominant-negative mutants in 1321N1 cells revealed that both isoforms regulated
      P2Y1 receptor signaling and trafficking, although only PKCdelta was capable of
      regulating P2Y12, in experiments in which PKC was directly activated by the
      phorbol ester phorbol 12-myristate 13-acetate (PMA). These results were
      paralleled in human platelets, in which PMA reduced subsequent ADP-induced P2Y1
      and P2Y12 receptor signaling. PKC isoform-selective inhibitors revealed that
      novel, but not conventional, isoforms of PKC regulate P2Y12 function, whereas
      both novel and classic isoforms regulate P2Y1 activity. It is also noteworthy
      that we studied receptor internalization in platelets by a radioligand binding
      approach showing that both receptors internalize rapidly in these cells. ADP
      induced P2Y1 receptor internalization is attenuated by PKC inhibitors, whereas
      that of the P2Y12 receptor is unaffected. Both P2Y1 and P2Y12 receptors can also
      undergo PMA-stimulated internalization, and here again, novel but not classic
      PKCs regulate P2Y12, whereas both novel and classic isoforms regulate P2Y1
      internalization. This study therefore is the first to reveal distinct roles for
      PKC isoforms in the regulation of platelet P2Y receptor function and trafficking.

PMID- 16804094
TI  - Potential drug-food interactions with pomegranate juice.

PMID- 16804095
TI  - Acid suppressive therapy use on an inpatient internal medicine service.
AB  - BACKGROUND: Use of acid suppressant medications has increased in both frequency
      and breadth in recent years. Data have indicated that questionable use of acid
      suppressants for non-accepted indications is common. OBJECTIVE: To assess the
      indications and prevalence of acid suppressants used by inpatients on admission
      and at discharge. METHODS: A retrospective chart review of 213 patients admitted
      to the University of Michigan Hospital non-critical care general medical service
      was conducted. Relevant medical history, acid suppressant drug used, and
      indications were collected from both inpatient medical records and discharge
      medication lists. RESULTS: Of the 213 patients reviewed, 29% were taking acid
      suppressants prior to admission, with 33% being proton pump inhibitors (PPIs).
      Once patients were admitted, acid suppressant use increased to 71% (152 of 213),
      with 84% PPIs, 11% histamine(2)-receptor antagonists, and 5% combination therapy.
      Based upon our criteria, only 10% (15 of 152) of those on acid suppressants were
      found to have an acceptable indication. In patients where any history of
      gastroesophageal reflux disorder (GERD) was deemed as an acceptable indication
      (32 other patients), 31% (47 of 152) had an acceptable indication. For the 137
      patients with non-accepted indications, 29% had no discernable indication and 38%
      were prescribed acid suppressants for corticosteroid-associated or stress ulcer
      prophylaxis. A history of gastrointestinal bleeds or peptic ulcer disease of more
      than 3 months since initial diagnosis or documented exacerbation of symptoms
      comprised 8% of the population. The aforementioned group of GERD patients made up
      23% of this group. Compared to the 29% of patients taking acid suppressants prior
      to admission, 54% (115 of 213) of patients were prescribed acid suppressants at
      discharge. If only recent exacerbations of GERD were deemed as long-term
      indications, 10% (12 of 115) of these patients were found to have accepted
      indications. If all GERDs were acceptable long-term indications, 27% (31 of 115)
      would have met criteria for acceptable outpatient use. CONCLUSIONS: There is
      considerable excess usage of acid suppressants in both the inpatient and
      outpatient settings.

PMID- 16804096
TI  - Pharmacist critique was ill-informed.
AB  - Pharmacists' ability to exercise "professional right of conscience" in dispensing
      emergency contraception, as well as the professionalism of pharmacists, has
      fallen under attack recently by the media, by state governments, and even by
      other healthcare professionals in published commentaries. This editorial
      discusses the controversy surrounding emergency contraceptives, the right of
      pharmacists to refuse to fill prescriptions that they consider morally
      objectionable, and the responsibility of pharmacists to provide medications in a
      timely and professional manner. The professionalism of pharmacy is also examined
      in light of the expanded scope of practice in which pharmacists increasingly find
      themselves practicing.

PMID- 16804097
TI  - Professional negligence: when practice goes wrong.
AB  - OBJECTIVE: To review the practice and legal principles of negligence law. CASE
      SUMMARY: An illustrative, fictional case is presented, based in part on facts
      gleaned from actual case law. A respected pharmacist, faced with the financial
      loss of his business, decided to engage in 2 creative but unethical schemes to
      increase his profit margin. In doing so, he violated federal Medicare law and
      placed a number of the patients who used his services at significant risk for
      medical complications. DISCUSSION: Negligence law has evolved over the past 30
      years in a manner that significantly increases the liability of the practicing
      pharmacist for both ordinary negligence actions and criminal negligence actions.
      In addition, the past decade has seen the expansion of Medicare Fraud and Abuse
      law such that it now represents an increasingly high risk area for every medical
      service provider, including the pharmacist. CONCLUSIONS: Professional practice in
      the US is highly regulated, governed by both case law and statutory law. Every
      practicing pharmacist should be aware of the law that governs his or her behavior
      to avoid both civil and criminal liability.

PMID- 16804098
TI  - Drug dosage adjustments according to renal function at hospital discharge.
AB  - BACKGROUND: Adequate dosing of medication in renal impairment to prevent
      hospitalizations and adverse reactions is a growing concern in the aging society.
      There are several dosing guidelines available, but structural use is uncommon.
      OBJECTIVE: To perform a retrospective analysis of the incidence of required
      versus implemented dosage adjustments according to guidelines in patients with
      renal insufficiency at discharge and evaluate specific determinants responsible
      for the percentage of overlooked dosage adjustments. METHODS: Medication and
      laboratory data were collected from patients at discharge during February and
      November 2004. For patients with a calculated creatinine clearance less than 51
      mL/min/1.73 m(2), the necessity for dosage adjustments was evaluated by
      pharmacists. All data were collected for further research and subsequent
      statistical analysis. RESULTS: At discharge, 237 of 647 (36.6%) patients had a
      calculated creatinine clearance less than 51 mL/min/1.73 m(2). Dosage adjustment
      based on renal function was necessary in 411 of 1718 (23.9%) of prescriptions.
      These adjustments were performed in 242 (58.9%) prescriptions and not performed
      in 169 (41.1%) cases. The risk of not adjusting the dosage was significantly
      associated with serum creatinine levels greater than 1.71 mg/dL and creatinine
      clearance less than 35 mL/min/1.73 m(2) (p < 0.05). The risk of not adjusting the
      dosage was also significantly associated with drugs producing severe consequences
      when dosing guidelines were overlooked (p < 0.05). CONCLUSIONS: In patients with
      a calculated creatinine clearance less than 51 mL/min/1.73 m(2), dosing according
      to their renal function can be improved. Because of the need and the association
      found in this study, an alert system could help prescribers and pharmacists to
      adapt drug dosage in patients with renal impairment.

PMID- 16804099
TI  - Does celecoxib potentiate the anticoagulant effect of warfarin? A randomized,
      double-blind, controlled trial.
AB  - BACKGROUND: The management of patients who are receiving warfarin therapy and
      have musculoskeletal problems that require treatment with a nonsteroidal
      antiinflammatory drug (NSAID) is problematic because NSAID use may increase the
      risk for bleeding. Cyclooxygenase-2 selective NSAIDs such as celecoxib may be
      less likely to promote gastrointestinal bleeding; however, there are concerns
      that they could potentiate the anticoagulation effect of warfarin. OBJECTIVE: To
      determine whether celecoxib potentiates the anticoagulant effect of warfarin, as
      measured by the international normalized ratio (INR). METHODS: We performed a
      randomized, controlled, crossover trial to assess the effect on INR of celecoxib
      versus codeine (control treatment) in 15 patients who were receiving warfarin
      therapy and required analgesic treatment for osteoarthritis. During Phase 1 of
      the study, patients were randomly allocated to receive celecoxib 200 mg/day or
      codeine phosphate 7-15 mg 3-4 times daily for 5 weeks. During Phase 2 of the
      study, patients stopped the first study medication and started the other study
      medication; there was no drug-free interval between phases. Weekly INR testing
      was performed during the 10 week study period. Adopting the intent-to-treat
      principle, we used generalized estimating equations to analyze the data. RESULTS:
      There was no significant difference in the mean INR values during each 5 week
      treatment period when patients received either celecoxib or codeine. There was,
      therefore, insufficient evidence to reject the hypothesis that these 2 treatments
      had an equal effect on the INR (mean difference [95% CI] 0.10 [-0.04 to 0.24]; p
      = 0.16) based on mean imputation. This finding was confirmed after we repeated
      the analysis with multiple imputations (mean difference [95% CI] 0.093 [-0.16 to
      0.35]; p = 0.47). CONCLUSIONS: Our results suggest that treatment with celecoxib
      does not potentiate the INR when taken with warfarin. Larger randomized trials
      are warranted to address the effects of coadministered warfarin and celecoxib on
      clinical outcomes.

PMID- 16804100
TI  - Quetiapine in the treatment of tic disorder.

PMID- 16804101
TI  - Pulmonary clinical pharmacy practice.

PMID- 16804102
TI  - Two splice variants of claudin-10 in the kidney create paracellular pores with
      different ion selectivities.
AB  - Members of the large claudin family of tight junction (TJ) proteins create the
      differences in paracellular conductance and charge selectivity observed among
      different epithelia. Previous studies demonstrated that ionic charge selectivity
      is influenced by acidic or basic amino acids on the first extracellular domain of
      claudins. We noted two alternatively spliced variants of claudin-10 in the
      database, 10a and 10b, which are predicted to encode two different first
      extracellular domains and asked whether this might be a novel mechanism to
      generate two different permselectivities from a single gene. Using quantitative
      PCR, we found that claudin-10b is widely expressed among tissues including the
      kidney; however, claudin-10a is unique to the kidney. Using a nondiscriminating
      antibody, we found that claudin-10 (a plus b) is expressed in most segments of
      the nephron. In situ hybridization, however, showed that mRNA for 10a is
      concentrated in the cortex, and mRNA for 10b is more highly expressed in the
      medulla. Expression in Madin-Darby canine kidney (MDCK) II and LLC-PK1 cells
      reveals that both variants form low-resistance pores, and that claudin-10b is
      more selective for cations than claudin-10a. Charge-reversing mutations of
      cationic residues on 10a reveal positions that contribute to its anion
      selectivity. We conclude that alternative splicing of claudin-10 generates unique
      permselectivities and might contribute to the variable paracellular transport
      observed along the nephron.

PMID- 16804103
TI  - Nocturnal polyuria in monosymptomatic nocturnal enuresis refractory to
      desmopressin treatment.
AB  - The transition from day to night is associated with a pronounced decline in
      diuresis with reductions in the amount of excreted water, electrolytes, and other
      end products of our metabolism. Failure to do so leads to a large urine output at
      night, a condition known as nocturnal polyuria, encountered in a large proportion
      of children with nocturnal enuresis. The aim of this study was to clarify the
      mechanisms responsible for the nocturnal polyuria seen in enuretics with
      inadequate response to desmopressin (dDAVP). Forty-six enuretics (7-14 yr of age)
      and fifteen age-matched controls were admitted for a 24-h protocol with
      standardized fluid and sodium intake, comprising urine collections, blood
      sampling, and blood pressure monitoring. We included patients with severe
      enuresis (5 +/- 1 wet nights/wk) showing <50% reduction in wet nights on dDAVP.
      We characterized the patients on the basis of their nocturnal urine production.
      The children with nocturnal polyuria excreted larger amounts of sodium and urea
      at night than nonpolyurics and controls. Solute-free water reabsorption as well
      as urinary arginine vasopressin and aquaporin-2 excretion were normal in
      polyurics, and no differences were found in atrial natriuretic peptide,
      angiotensin II, aldosterone, and renin levels. Urinary prostaglandin E2 (PGE2)
      excretion was significantly higher in polyurics. The nocturnal polyuria in
      children with dDAVP-resistant nocturnal enuresis seems to be the result of
      augmented sodium and urea excretion. The high urinary PGE2 levels found in these
      children point toward a role for increased prostaglandin synthesis in the
      pathogenesis of enuresis-related polyuria.

PMID- 16804104
TI  - Vascular endothelial growth factor administration does not improve microvascular
      disease in the salt-dependent phase of post-angiotensin II hypertension.
AB  - Renal microvascular injury and tubulointerstitial inflammation may provide a
      potential mechanism for the development of salt-sensitive hypertension.
      Therefore, we hypothesized that vascular endothelial growth factor (VEGF)
      administration would prevent the development of salt-sensitive hypertension
      induced by ANG II. Infusion of ANG II in rats for 2 wk led to an elevation in
      blood pressure and an increase in blood urea nitrogen. Prominent tubular injury,
      focal areas of peritubular capillary loss accompanied by a decrease in urinary
      nitrites, thickening of the afferent arteriole, and an elevation in systemic and
      renal VEGF protein levels also occurred. In separate studies, animals were
      infused with ANG II and then placed on a low-salt diet for 1 wk. At this point,
      the animals were paired on the basis of weight and blood pressure and treated
      with either VEGF(121) or vehicle subcutaneously for 8 wk while being fed a high
      salt diet. During the treatment period, a spontaneous improvement in many
      parameters, including both renal function and healing of the peritubular
      capillaries, occurred to the same degree in both vehicle- and VEGF(121)-treated
      rats. VEGF(121) significantly reduced blood pressure and accelerated the recovery
      of tubular injury. In contrast, vehicle-treated rats demonstrated a persistent
      increase in afferent arteriolar media-to-lumen ratio, which was further enhanced
      in rats treated with VEGF(121). Therefore, VEGF therapy has only limited benefits
      on the healing of renal lesions in the salt-dependent phase of post-ANG II
      mediated hypertension.

PMID- 16804105
TI  - Silencing and overexpression of the gamma-subunit of Na-K-ATPase directly affect
      survival of IMCD3 cells in response to hypertonic stress.
AB  - The gamma-subunit of Na-K-ATPase is robustly expressed in inner medullary
      collecting duct (IMCD)3 cells either acutely challenged or adapted to
      hypertonicity but not under isotonic conditions. Circumstantial evidence suggests
      that this protein may be important for the survival of renal cells in a
      hypertonic environment. However, no direct proof for such a contention has been
      forthcoming. The complete mRNA sequences of either gamma-subunit isoforms were
      spliced into an expression vector and transfected into IMCD3 cells. Multiple
      clones stably expressed gamma-subunit protein under isotonic conditions. Clones
      expressing the gamma(b) isoform showed enhanced survival at lethal acute
      hypertonicity compared with either gamma(a) isoform or empty vector (control)
      expressing clones. We also evaluated the loss of gamma-subunit expression on the
      survival of IMCD3 cells exposed to hypertonicity employing silencing RNA
      techniques. Multiple stable gamma-subunit-specific siRNA clones were obtained and
      exposed to sublethal hypertonicity. Under these conditions, both the level of
      gamma mRNA and protein was essentially undetectable. The impact of silencing
      gamma-subunit expression resulted in a 70% reduction at 48 h (P < 0.01) in cell
      survival compared with empty vector (control) clones. gamma siRNA clones showed a
      45% decrease in myo-inositol uptake compared with controls after an 18-h exposure
      to sublethal hypertonicity. Taken together, these data demonstrate a direct and
      critical role of the gamma-subunit on IMCD3 cell survival and/or adaptation in
      response to ionic hypertonic stress.

PMID- 16804107
TI  - Molecular cloning and functional characterization of novel zinc transporter
      rZip10 (Slc39a10) involved in zinc uptake across rat renal brush-border membrane.
AB  - Previously, in our laboratory a 40-kDa zinc transporter protein was purified and
      functionally reconstituted in proteoliposomes (Kumar R, Prasad R. Biochim Biophys
      Acta 1419: 23-32, 1999). Furthermore, we now report the identification of
      Slc39a10 cDNA encoding the 40-kDa zinc transporter protein by isolating a cloned
      DNA complementary to zinc transporter mRNA. cDNA was constructed from
      immunoenriched mRNA encoding the zinc transporter. cDNA was inserted into pBR322
      using poly(dC)- poly(dG) tailing. Escherichia coli DH5alpha cells were
      transformed, and colonies were screened for zinc transporter cDNA by insertional
      inactivation. Plasmid DNA was purified from the ampicillin-sensitive clones, and
      the cDNA was sequenced from both strands. A basic local alignment research tool
      (BLAST) search of cDNA revealed that it belongs to the Slc39 gene family of zinc
      transporters and was designated as Slc39a10. Zinc transporter protein deduced on
      the basis of cDNA sequence was named rZip10 and consists of 385 amino acids with
      9 predicted transmembrane domains. The Slc39a10 gene was abundantly expressed in
      both rat and human tissues. Increased extracellular zinc concentration resulted
      in upregulation of Slc39a10 in LLC-PK(1) cells expressing rZip10, which was
      downregulated at higher zinc concentrations. These cells accumulated more zinc
      than control cells. rZip10-mediated zinc uptake activity was time-, temperature-,
      and concentration-dependent and saturable which followed Michaelis-Menten
      kinetics with a K(m) of 19.2 microM and V(max) of 50 pmol x min(-1) x mg protein(
      1). This activity was competitively inhibited by cadmium with K(i) of 91 microM.
      rZip10-mediated zinc uptake was inhibited by COOH group-modifying agents such as
      DCC. Immunofluorescence studies showed that rZip10 localizes to the plasma
      membrane of LLC-PK(1) cells.

PMID- 16804106
TI  - Sustained renal interstitial macrophage infiltration following chronic
      angiotensin II infusions.
AB  - Chronic angiotensin (ANG) II infusions into rats lead to augmented intrarenal
      levels of ANG II and inflammatory factors, impaired renal function, and
      progressive hypertension. Residual effects persist after cessation of ANG II
      infusions, as manifested by a hypertensive response to high-salt intake. This
      study was performed to determine the residual cytokines and chemokines following
      the cessation of ANG II infusion. Male Sprague-Dawley rats, maintained on a
      normal diet, received either a sham operation or continuous ANG II infusion (120
      ng/min) subcutaneously via minipumps. The ANG II-infused rats were further
      subdivided into three subgroups. Minipumps were removed on day 12 with subsequent
      harvesting of kidneys at 0, 3, and 6 days after cessation of ANG II infusion.
      After 12 days of ANG II infusion, systolic blood pressure, interstitial fibrosis,
      preglomerular hypertrophy, and interstitial macrophage infiltration were
      significantly enhanced compared with the shams. By 3 days following the cessation
      of ANG II infusion, systolic blood pressure was normalized; however, interstitial
      fibrosis and preglomerular hypertrophy were still present. Furthermore, increased
      interstitial macrophage infiltration was still present 6 days after cessation of
      ANG II infusion. Importantly, augmented mRNA levels of monocyte chemotactic
      protein (MCP)-1 (1.55 +/- 0.15 vs. 1.00 +/- 0.13, relative ratio) and
      transforming growth factor (TGF)-beta(1) (1.52 +/- 0.16 vs. 1.00 +/- 0.08)
      persisted 6 days after the withdrawal of ANG II infusion (1.60 +/- 0.20 for MCP-1
      and 1.43 +/- 0.17 for TGF-beta(1)). Thus, the ANG II-induced activation of MCP-1
      and TGF-beta(1) is sustained and may account for the persistent effect of chronic
      ANG II infusions on interstitial macrophage infiltration, suggesting a possible
      mechanism for the development of salt sensitivity in ANG II-dependent
      hypertension.

PMID- 16804108
TI  - Suppression of erythropoiesis in malarial anemia is associated with hemozoin in
      vitro and in vivo.
AB  - Malarial anemia is a global public health problem and is characterized by a low
      reticulocyte response in the presence of life-threatening hemolysis. Although
      cytokines, in particular tumor necrosis factor-alpha (TNF-alpha), can suppress
      erythropoiesis, the grossly abnormal bone marrow morphology indicates that other
      factors may contribute to ineffective erythropoiesis. We hypothesized that the
      cytotoxic hemozoin (Hz) residues from digested hemoglobin (Hb) significantly
      contribute to abnormal erythropoiesis. Here, we show that not only isolated Hz,
      but also delipidated Hz, inhibits erythroid development in vitro in the absence
      of TNF-alpha. However, when added to cultures, TNF-alpha synergizes with Hz to
      inhibit erythropoiesis. Furthermore, we show that, in children with malarial
      anemia, the proportion of circulating monocytes containing Hz is associated with
      anemia (P < .001) and reticulocyte suppression (P = .009), and that this is
      independent of the level of circulating cytokines, including TNF-alpha. Plasma Hz
      is also associated with anemia (P < .001) and reticulocyte suppression (P = .02).
      Finally, histologic examination of the bone marrow of children who have died from
      malaria shows that pigmented erythroid and myeloid precursors are associated with
      the degree of abnormal erythroid development. Taken together, these observations
      provide compelling evidence for inhibition of erythropoiesis by Hz.

PMID- 16804110
TI  - Timing of neutrophil tissue repopulation predicts restoration of innate immune
      protection in a murine bone marrow transplantation model.
AB  - It has been suggested that neutrophil tissue repopulation following bone marrow
      transplantation (BMT) serves as an earlier and more relevant marker of
      susceptibility to infection than circulating neutrophil counts. In a previous
      study using an oral rinse protocol, we found that oral neutrophil recovery always
      preceded blood neutrophil engraftment and that the day of oral neutrophil
      detection served as a predictor of patient susceptibility to infection after BMT.
      Consequently, we have developed and validated a mouse BMT model which uses bone
      marrow transplants containing enhanced green fluorescent protein-expressing
      neutrophils to follow neutrophil tissue repopulation after BMT. Using this in
      vivo cell migration model, we assessed the significance of neutrophil tissue
      recruitment kinetics with neutrophil functionality and in vivo bacterial killing
      after BMT. Using the animal model, we have demonstrated that protection against
      bacterial infection is conferred at the time of neutrophil tissue delivery, which
      always occurs before neutrophils are detected in the blood. We therefore conclude
      that neutrophil tissue recovery is an early measure of the restoration of
      cellular innate immune function after BMT. This model will help us better
      understand the factors regulating neutrophil recruitment to the tissues.

PMID- 16804109
TI  - Molecular events contributing to cell death in malignant human hematopoietic
      cells elicited by an IgG3-avidin fusion protein targeting the transferrin
      receptor.
AB  - We have previously reported that an anti-human transferrin receptor IgG3-avidin
      fusion protein (anti-hTfR IgG3-Av) inhibits the proliferation of an
      erythroleukemia-cell line. We have now found that anti-hTfR IgG3-Av also inhibits
      the proliferation of additional human malignant B and plasma cells. Anti-hTfR
      IgG3-Av induces internalization and rapid degradation of the TfR. These events
      can be reproduced in cells treated with anti-hTfR IgG3 cross-linked with a
      secondary Ab, suggesting that they result from increased TfR cross-linking.
      Confocal microscopy of cells treated with anti-hTfR IgG3-Av shows that the TfR is
      directed to an intracellular compartment expressing the lysosomal marker LAMP-1.
      The degradation of TfR is partially blocked by cysteine protease inhibitors.
      Furthermore, cells treated with anti-hTfR IgG3-Av exhibit mitochondrial
      depolarization and activation of caspases 9, 8, and 3. The mitochondrial damage
      and cell death can be prevented by iron supplementation, but cannot be fully
      blocked by a pan-caspase inhibitor. These results suggest that anti-hTfR IgG3-Av
      induces lethal iron deprivation, but the resulting cell death does not solely
      depend on caspase activation. This report provides insights into the mechanism of
      cell death induced by anti-TfR Abs such as anti-hTfR IgG3-Av, a molecule that may
      be useful in the treatment of B-cell malignancies such as multiple myeloma.

PMID- 16804111
TI  - Thrombotic complications in childhood acute lymphoblastic leukemia: a meta
      analysis of 17 prospective studies comprising 1752 pediatric patients.
AB  - The risk of thrombosis in children with acute lymphoblastic leukemia (ALL)
      reportedly ranges between 1% and 37%. Epidemiologic studies have usually been
      hampered by small numbers, making accurate estimates of thrombosis risk in ALL
      patients very difficult. The aim of this study was to better estimate the
      frequency of this complication and to define how the disease, its treatment, and
      the host contribute to its occurrence. We made an attempt to combine and analyze
      all published data on the association between pediatric ALL and thrombosis, by
      using a meta-analytic method. The rate of thrombosis in 1752 children from 17
      prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on
      several factors. Most of the events occurred during the induction phase of
      therapy. Lower doses of asparaginase (ASP) for long periods were associated with
      the highest incidence of thrombosis, as were anthracyclines and prednisone
      (instead of dexamethasone). The presence of central lines and of thrombophilic
      genetic abnormalities also appeared to be frequently associated with thrombosis.
      In conclusion, the overall thrombotic risk in ALL children was significant, and
      the subgroup analysis was able to identify high-risk individuals, a finding that
      will hopefully guide future prospective studies aimed at decreasing this risk.

PMID- 16804113
TI  - Marked increased risk of Epstein-Barr virus-related complications with the
      addition of antithymocyte globulin to a nonmyeloablative conditioning prior to
      unrelated umbilical cord blood transplantation.
AB  - Umbilical cord blood (UCB) is increasingly used as an alternative source of
      hematopoietic stem cells for transplantation for patients who lack a suitable
      sibling donor. Despite concerns about a possible increased risk of Epstein-Barr
      virus (EBV) posttransplantation lymphoproliferative disorder (PTLD) after UCB
      transplantation, early reports documented rates of PTLD comparable to those
      reported after HLA-matched unrelated marrow myeloablative (MA) transplantations.
      To further investigate the incidence of EBV PTLD after UCB transplantation and
      potential risk factors, we evaluated the incidence of EBV-related complications
      in 335 patients undergoing UCB transplantation with an MA or nonmyeloablative
      (NMA) preparative regimen. The incidence of EBV-related complications was a 4.5%
      overall, 3.3% for MA transplantations, and 7% for NMA transplantations. However,
      the incidence of EBV-related complications was significantly higher in a subset
      of patients treated with an NMA preparative regimen that included antithymocyte
      globulin (ATG) versus those that did not (21% vs 2%; P < .01). Nine of 11
      patients who developed EBV PTLD were treated with rituximab (anti-CD20 antibody),
      with the 5 responders being alive and disease free at a median of 26 months. Use
      of ATG in recipients of an NMA preparative regimen warrants close monitoring for
      evidence of EBV reactivation and potentially preemptive therapy with rituximab.

PMID- 16804114
TI  - Non-side-population hematopoietic stem cells in mouse bone marrow.
AB  - Most hematopoietic stem cells (HSCs) are assumed to reside in the so-called side
      population (SP) in adult mouse bone marrow (BM). We report the coexistence of non
      SP HSCs that do not significantly differ from SP HSCs in numbers, capacities, and
      cell-cycle states. When stained with Hoechst 33342 dye, the CD34(-/low) c
      Kit(+)Sca-1(+)lineage marker(-) (CD34(-)KSL) cell population, highly enriched in
      mouse HSCs, was almost equally divided into the SP and the main population (MP)
      that represents non-SP cells. Competitive repopulation assays with single or 30
      SP- or MP-CD34(-)KSL cells found similar degrees of repopulating activity and
      frequencies of repopulating cells for these populations. Secondary
      transplantation detected self-renewal capacity in both populations. SP analysis
      of BM cells from primary recipient mice suggested that the SP and MP phenotypes
      are interconvertible. Cell-cycle analyses revealed that CD34(-)KSL cells were in
      a quiescent state and showed uniform cell-cycle kinetics, regardless of whether
      they were in the SP or MP. Bcrp-1 expression was similarly detected in SP- and MP
      CD34(-)KSL cells, suggesting that the SP phenotype is regulated not only by Bcrp
      1, but also by other factors. The SP phenotype does not specify all HSCs; its
      identity with stem cell function thus is unlikely.

PMID- 16804112
TI  - JAK2T875N is a novel activating mutation that results in myeloproliferative
      disease with features of megakaryoblastic leukemia in a murine bone marrow
      transplantation model.
AB  - Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia
      associated with a poor prognosis. However, there are relatively few insights into
      the genetic etiology of AMKL. We developed a screening assay for mutations that
      cause AMKL, based on the hypothesis that constitutive activation of STAT5 would
      be a biochemical indicator of mutation in an upstream effector tyrosine kinase.
      We screened human AMKL cell lines for constitutive STAT5 activation, and then
      used an approach combining mass spectrometry identification of tyrosine
      phosphorylated proteins and growth inhibition in the presence of selective small
      molecule tyrosine kinase inhibitors that would inform DNA sequence analysis of
      candidate tyrosine kinases. Using this strategy, we identified a new JAK2T875N
      mutation in the AMKL cell line CHRF-288-11. JAK2T875N is a constitutively
      activated tyrosine kinase that activates downstream effectors including STAT5 in
      hematopoietic cells in vitro. In a murine transplant model, JAK2T875N induced a
      myeloproliferative disease characterized by features of AMKL, including
      megakaryocytic hyperplasia in the spleen; impaired megakaryocyte
      polyploidization; and increased reticulin fibrosis of the bone marrow and spleen.
      These findings provide new insights into pathways and therapeutic targets that
      contribute to the pathogenesis of AMKL.

PMID- 16804115
TI  - Enhanced susceptibility to arterial thrombosis in a murine model of
      hyperhomocysteinemia.
AB  - Hyperhomocysteinemia is a risk factor for thrombosis, but the mechanisms are not
      well defined. We tested the hypothesis that hyperhomocysteinemia accelerates
      arterial thrombosis in mice. Mice heterozygous for a targeted disruption of the
      cystathionine beta-synthase gene (Cbs+/-) and wild-type littermates (Cbs+/+) were
      fed either a control diet or a high methionine/low folate (HM/LF) diet for 6 to 8
      months to produce graded hyperhomocysteinemia. The time to occlusion of the
      carotid artery after photochemical injury was shortened by more than 50% in
      Cbs+/+ or Cbs+/- mice fed the HM/LF diet (P < .001 versus control diet). Carotid
      artery thrombosis was not accelerated in mice deficient in endothelial nitric
      oxide synthase (Nos3), which suggests that decreased endothelium-derived nitric
      oxide is not a sufficient mechanism for enhancement of thrombosis. Cbs+/+ and
      Cbs+/- mice fed the HM/LF diet had elevated levels of reactive oxygen species in
      the carotid artery, increased aortic expression of the NADPH oxidase catalytic
      subunit, Nox4, and decreased activation of anticoagulant protein C in the aorta
      (P < .05 versus control diet). We conclude that hyperhomocysteinemia enhances
      susceptibility to arterial thrombosis through a mechanism that is not caused by
      loss of endothelium-derived nitric oxide but may involve oxidative stress and
      impairment of the protein C anticoagulant pathway.

PMID- 16804116
TI  - Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype
      more similar to chronic lymphocytic leukemia than multiple myeloma.
AB  - Waldenstrom macroglobulinemia (WM) is a B-cell malignancy characterized by the
      ability of the B-cell clone to differentiate into plasma cells. Although the
      clinical syndrome and the pathologic characteristics are well defined, little is
      known about its biology and controversy still exists regarding its cell of
      origin. In this gene-expression study, we compared the transcription profiles of
      WM with those of other malignant B cells including (chronic lymphocytic leukemia
      [CLL] and multiple myeloma [MM]) as well as normal cells (peripheral-blood B
      cells and bone marrow plasma cells). We found that WM has a homogenous gene
      expression regardless of 6q deletion status and clusters with CLL and normal B
      cells on unsupervised clustering with very similar expression profiles. Only a
      small gene set has expression profiles unique to WM compared to CLL and MM. The
      most significantly up-regulated gene is IL6 and the most significantly associated
      pathway for this set of genes is MAPK signaling. Thus, IL6 and its downstream
      signaling may be of biologic importance in WM. Further elucidation of the role of
      IL-6 in WM is warranted as this may offer a potential therapeutic avenue.

PMID- 16804117
TI  - Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in
      congenital neutropenia.
AB  - Severe congenital neutropenia (SCN) is characterized by neutropenia, recurrent
      bacterial infections, and maturation arrest in the bone marrow. Although many
      cases have mutations in the ELA2 gene encoding neutrophil elastase, a significant
      proportion remain undefined at a molecular level. A mutation (Leu270Pro) in the
      gene encoding the Wiskott-Aldrich syndrome protein (WASp) resulting in an X
      linked SCN kindred has been reported. We therefore screened the WAS gene in 14
      young SCN males with wild-type ELA2 and identified 2 with novel mutations, one
      who presented with myelodysplasia (Ile294Thr) and the other with classic SCN
      (Ser270Pro). Both patients had defects of immunologic function including a
      generalized reduction of lymphoid and natural killer cell numbers, reduced
      lymphocyte proliferation, and abrogated phagocyte activity. In vitro culture of
      bone marrow progenitors demonstrated a profound reduction in neutrophil
      production and increased levels of apoptosis, consistent with an intrinsic
      disturbance of normal myeloid differentiation as the cause of the neutropenia.
      Both mutations resulted in increased WASp activity and produced marked
      abnormalities of cytoskeletal structure and dynamics. Furthermore, these results
      also suggest a novel cause of myelodysplasia and that male children with
      myelodysplasia and disturbance of immunologic function should be screened for
      such mutations.

PMID- 16804118
TI  - Outbreak in Alberta of community-acquired (USA300) methicillin-resistant
      Staphylococcus aureus in people with a history of drug use, homelessness or
      incarceration.
AB  - BACKGROUND: The USA300 strain of community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) can cause severe infection and is increasingly
      recognized as a cause of community outbreaks. In 2004, an outbreak was identified
      in the Calgary Health Region (CHR). METHODS: MRSA isolates were identified with
      standard methods at a central regional laboratory and typed via pulsed-field gel
      electrophoresis (PFGE). Isolates were tested by PCR for mecA, Panton-Valentine
      leukocidin (PVL), SCCmec, and spa genes. Cases were defined as such if a clinical
      isolate of the USA300 strain was noted between January 1 and September 30, 2004,
      and the patient had lived or traveled in CHR within 2 years before symptom onset.
      Demographic, clinical and risk data on all such cases were collected from several
      sources for statistical analysis. A case was defined as high-risk if the patient
      had a history of drug use, homelessness or incarceration. RESULTS: Of 40 isolates
      with the USA300 PFGE pattern, all tested positive for PVL, SCCmec type IVa and
      spa type 008. Almost all infections (39/40, 98%) involved skin and soft tissues,
      except for 1 death from necrotizing hemorrhagic pneumonia; a notable proportion
      (38%) required hospital admission or intravenous antimicrobial therapy. The
      outbreak centred on the high-risk population in CHR (70%; risk ratio 169.4, 95%
      confidence interval 86.1-333.0). INTERPRETATION: People with histories of illicit
      drug use, homelessness or recent incarceration were at highest risk for infection
      with CA-MRSA. The emergence and spread of this virulent strain has important
      implications for treatment and public health in Canada.

PMID- 16804119
TI  - Public health implications of MRSA in Canada.

PMID- 16804120
TI  - Community-acquired MRSA: a practitioner's guide.

PMID- 16804121
TI  - A man with recurrent furunculosis.

PMID- 16804122
TI  - Osteoporosis treatment: raloxifene (Evista) and stroke mortality.

PMID- 16804123
TI  - A priori dietary omega-3 lipid supplementation results in local pancreatic
      macrophage and pulmonary inflammatory response attenuation in a model of
      experimental acute edematous pancreatitis (AEP).
AB  - BACKGROUND: Acute pancreatitis is often complicated by multiorgan dysfunction,
      which is postulated to occur in part by macrophage infiltration into the
      pancreas. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, is the principal
      biologic component of fish oil and has clinically and experimentally been
      demonstrated to be anti-inflammatory. We hypothesized that dietary EPA
      supplementation before the induction of pancreatitis would attenuate both M
      mediated local pancreatic and systemic pulmonary inflammatory response in an in
      vivo model of acute edematous pancreatitis (AEP). METHODS: Male Sprague-Dawley
      (SD) rats were pretreated 2 times per day with oral gavage with EPA (omega-3
      fatty acid; 5 mg/kg/dose) or omega-6 fatty acid control (5 mg/kg/dose) or saline
      (equal volume) for 2 weeks. AEP was induced in omega-3, omega-6, and saline
      pretreated rats by 5 hourly subcutaneous (SC) injections of cerulein. Pancreas,
      lung, and serum were harvested 3 hours after the last cerulein injection.
      Severity of pancreatitis was confirmed by serum amylase and by histopathologic
      score. Pancreatic macrophage infiltration was assessed by confocal fluorescent
      microscopy, and pulmonary leukocyte respiratory burst (LRB) analysis was
      performed on mononuclear cells obtained from bronchioalveolar lavage (BAL).
      RESULTS: All animals demonstrated acute pancreatitis through hyperamylasemia and
      histopathologic examination. Confocal analysis demonstrated significantly lower
      macrophage infiltration, and BAL analysis by flow cytometry demonstrated
      significantly lower (p < .05) LRB in the omega-3-treated group compared with the
      omega-6 and the saline pancreatitis group. CONCLUSIONS: Attenuation of both
      pancreatic MPhi inflammatory response and pulmonary leukocyte respiratory burst
      in AEP by EPA supports further investigation into the potential role for EPA
      dietary supplementation in the progression of pancreatitis-associated sequelae.

PMID- 16804124
TI  - Appearance of individual amino acid concentrations in arterial blood during
      steady-state infusions of different amino acid formulations to ICU patients in
      support of whole-body protein metabolism.
AB  - BACKGROUND: Previous work has demonstrated a relationship between arterial amino
      acid concentrations and uptake of amino acids across peripheral tissues in
      healthy volunteers, as well as in chronically and acutely ill patients. The aim
      of the present study was to evaluate whether different amino acid profiles in
      commercially available amino acid formulations are translated into significantly
      different arterial amino acid concentrations presumably high enough to promote
      protein metabolism in intensive care unit (ICU) patients. METHODS: Nonprotein
      calories (60% glucose: 40% lipid) were simultaneously and constantly infused over
      72 hours. Different free amino acid solutions were infused at random to each
      patient for 24 hours in order to determine the appearance of steady-state
      arterial concentrations of individual amino acids. Basal metabolic and nutrition
      states were defined after a 12-hour infusion period with glucose in each patient.
      Healthy volunteers receiving a standardized oral meal served as reference
      subjects in measurements of venous amino acid concentrations after normal oral
      food intake. RESULTS: The sum of all amino acids in arterial plasma increased
      significantly during steady-state infusions of all the free amino acid solutions
      vs basal state in ICU patients. Only glutamine, taurine, and tyrosine did not
      increase at all vs basal state during steady-state infusions of the 3
      formulations. Alanine, arginine, citrulline, glycine, histidine, serine,
      methionine, phenylalanine, valine, and ornithine showed different concentration
      among the amino acid solutions during infusions. Healthy volunteers had
      significantly higher overall concentrations of amino acids in both fasted and fed
      state compared with ICU patients, which indicates that free amino acid solutions
      remain a limiting component in artificial nutrition to patients to promote
      arterial amino acid concentrations in the artificially fed state. CONCLUSIONS: It
      appears important to continue further improvement of composition profile in
      solutions of free amino acids to promote adequate uptake across organ beds in
      promotion of protein balance in artificially nourished patients.

PMID- 16804125
TI  - Olive oil-based lipid emulsion's neutral effects on neutrophil functions and
      leukocyte-endothelial cell interactions.
AB  - BACKGROUND: Infection remains a drawback of parenteral nutrition (PN), probably
      related, among other factors, to immunosuppressive effects of its lipid
      component. Newer preparations may have lesser immunosuppressive impact. This
      study examines the effects of an olive oil-based lipid emulsion (long-chain
      triacylglycerols-monounsaturated fatty acids [LCT-MUFA]; ClinOleic) on various
      functions of human neutrophils in vitro and on rat leukocyte-endothelial cell
      interactions in vivo compared with LCT (Intralipid) and 50% LCT-50% medium-chain
      triacylglycerols (MCT; Lipofundin) mixture. METHODS: Neutrophils isolated from
      healthy donors were incubated with concentrations (0.03-3 mmol/L) of lipid
      emulsions encompassing clinically relevant levels. In vivo leukocyte recruitment
      was studied with intravital microscopy within rat mesenteric microcirculation.
      RESULTS: LCT-MUFA (3 mmol/L) did not alter the N-formyl-Met-Leu-Phe (FMLP)
      induced rise in [Ca2+]i, oxidative burst, chemotaxis, and elastase release,
      whereas LCT-MCT decreased [Ca2+]i and chemotaxis and increased oxidative burst.
      FMLP-induced LTB4 production was augmented by lipid emulsions. Serum-opsonized
      zymosan-induced phagocytosis was unaltered by lipid emulsions. Basal and FMLP
      induced CD11b expression was unaffected by lipid emulsions. Lipopolysaccharide
      (LPS)-induced TNF-alpha, IL-1beta and IL-8 mRNA, and protein expression was
      unaltered by LCT-MUFA, whereas LCT and LCT-MCT decreased IL-1beta mRNA and
      protein. LCT-MUFA did not alter apoptosis, but LCT increased apoptosis in absence
      and presence of GM-CSF. LPS (1 microg/mL)-induced increase in leukocyte rolling
      flux, adhesion, and emigration was inhibited by LCT and LCT-MCT but unaffected in
      LCT-MUFA-treated rats. Immunohistochemistry showed LPS-induced increase in P
      selectin expression attenuated by LCT and LCT-MCT but not LCT-MUFA. CONCLUSIONS:
      LCT-MUFA showed lower in vitro and in vivo impact on neutrophil function compared
      with LCT and LCT-MCT.

PMID- 16804126
TI  - Crocetin inhibits mRNA expression for tumor necrosis factor-alpha, interleukin
      1beta, and inducible nitric oxide synthase in hemorrhagic shock.
AB  - BACKGROUND: Inflammatory factors play an important role in cellular damage after
      shock and resuscitation. Crocetin, a saffron-derived carotenoid, has been shown
      to improve postshock recovery of cellular adenosine triphosphate (ATP) and to
      increase overall survival in an experimental model of hemorrhagic shock. The
      hypothesis of the present study is that treatment with crocetin at the beginning
      of resuscitation suppresses subsequent expression of messenger ribonucleic acid
      (mRNA) for tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1beta) and
      inducible nitric oxide synthase (iNOS). METHODS: Male Sprague-Dawley rats (n =
      45, 350 +/- 30 g) were randomly assigned to 5 groups of 9 animals each. After
      anesthesia with isoflurane, the femoral artery and vein were surgically
      cannulated. Hemorrhagic shock was induced by withdrawing blood through the
      arterial cannula until the mean arterial pressure (MAP) was 25-30 mm Hg and
      maintained at the level for 30 minutes with further withdrawals. Resuscitation
      was carried out by giving 21 mL/kg Ringer's lactate (LR) and returning the shed
      blood, with or without the initial administration of crocetin (2 mg/kg). Controls
      were normal (anesthesia only), sham (surgical preparation), and shock
      (preparation and shock). Rats were killed 30 minutes after completion of
      resuscitation. Liver samples were collected for reverse transcription-polymerase
      chain reaction (RT-PCR) analysis of mRNA (TNF-alpha, IL-1beta, iNOS, and beta
      actin). RESULTS: Liver mRNA expression for TNF-alpha, IL-1beta, and iNOS was
      found in more animals in the shock and shock-plus-resuscitation groups than in
      the sham control group. The group resuscitated from shock with crocetin had mRNA
      expression for TNF-alpha, IL-1beta, and iNOS in fewer animals than either of the
      other shock groups and was no different from the sham control group. CONCLUSIONS:
      Crocetin modified the hepatic mRNA expression of cytokines and iNOS in a shock
      model. This agent continues to show promise as a potential treatment for
      hemorrhagic shock.

PMID- 16804128
TI  - Phase angle from bioelectrical impedance analysis: population reference values by
      age, sex, and body mass index.
AB  - BACKGROUND: The use of bioelectrical impedance phase angle has been recommended
      as a prognostic tool in the clinical setting, but published reference data bases
      are discrepant and incomplete (eg, they do not consider body mass index [BMI],
      and data are lacking for children). METHODS: Phase angle reference values
      stratified by age, sex, and BMI were generated in a large German data base of
      15,605 children and adolescents and 214,732 adults, and the determinants of phase
      angle values were assessed. The reference values were applied to 3 groups of
      patients and compared with previously published reference values from the United
      States and Switzerland. RESULTS: Gender and age were the main determinants of
      phase angle in adults, with men and younger subjects having higher phase angles.
      In children and adolescents, age and BMI were the main determinants of phase
      angle. In normal and overweight adults, phase angle increased with increasing
      BMI, but there was an inverse association at a BMI >40 kg/m2. In cirrhosis, the
      prevalence of a low phase angle increased with the state of disease, whereas it
      was not different between patients with the metabolic syndrome and controls.
      There are considerable differences between phase angle reference values from
      different populations. These differences are not explained by age or BMI and may
      be due to differences between impedance analyzers. CONCLUSION: The determinants
      of phase angle differ between adults and children. In adults, the influence of
      BMI on phase angle depended on the BMI range. The prognostic value of phase angle
      may differ in different clinical settings. The use of population-specific and
      probably impedance-analyzer-specific reference values for phase angle is
      recommended.

PMID- 16804127
TI  - Effects of preoperative flavonoid supplementation on different organ functions in
      rats.
AB  - BACKGROUND: Previously it has been reported that preoperative feeding preserves
      heart function in rats after intestinal ischemia-reperfusion. To further improve
      postoperative organ function, bioactive nutrition compounds were selected in
      vitro against the xanthine oxidase radical cascade, an enzyme suggested to play a
      key role in the induction of single- or multiple-organ dysfunction. METHODS:
      Flavonoids were selected in vitro for their capacity to (1) inhibit xanthine
      oxidase, (2) scavenge superoxide, and (3) scavenge peroxylradicals. The most
      bioactive flavonoids were added to the preoperative nutrition to study their
      effect on postintestinal ischemia-reperfusion organ function. RESULTS: A
      combination of flavonoids selected on basis of effective flavonoid xanthine
      oxidase inhibition and superoxide scavenging resulted in increased superoxide
      scavenging. In vivo, the selected flavonoid mixture significantly lowered
      postischemic intestinal apoptosis and intestinal oxidative stress indicated by
      malondialdehyde concentration when compared with ischemia-reperfusion fasted and
      sham-fasted animals. Moreover, this flavonoid mixture significantly lowered
      plasma creatinine and urea concentration, both indicating a better postoperative
      kidney function. Furthermore, oxidative stress measured as this flavonoid mixture
      when compared with control significantly lowered plasma malondialdehyde
      concentration in fed rats. CONCLUSIONS: Coadministration of bioactive flavonoid
      mixture to preoperative nutrition, in contrast to fasting, attenuates ischemia
      reperfusion injury by preserving kidney function in the rat and decreasing
      apoptosis in the intestine.

PMID- 16804129
TI  - Choline deficiency is associated with increased risk for venous catheter
      thrombosis.
AB  - BACKGROUND: Patients with intestinal failure who require long-term parenteral
      nutrition (PN) develop catheter thrombosis as a complication. This patient group
      may also develop choline deficiency because of a defect in the hepatic
      transsulfuration pathway in the setting of malabsorption. This study was
      undertaken to determine whether choline deficiency is a risk factor for
      development of catheter thrombosis. METHODS: Plasma free and phospholipid-bound
      choline concentrations were measured in a group of 41 patients that required long
      term PN. Episodes of catheter thrombosis from onset of PN to the time of blood
      testing were recorded. RESULTS: Sixteen (39%) patients developed catheter
      thrombosis, and 5 of these had recurrent catheter thrombosis. Plasma free choline
      was 7.7 +/- 2.7 nmol/mL in patients with no history of catheter thrombosis and
      6.2 +/- 1.7 nmol/mL in patients with previous catheter thrombosis (p = .076 by
      Wilcoxon rank-sum test). The partial correlation between plasma free choline
      concentration and the frequency of clots after controlling for catheter duration
      was r = -0.33 (p = .038). The relative risk for catheter thrombosis in subjects
      with a plasma free choline concentration <8 nmol/mL was 10.0, 95% confidence
      interval (1.134-88.167). Plasma phospholipid-bound choline concentration was
      2191.7 +/- 679.0 nmol/mL in patients with previous catheter thrombosis and 2103.3
      +/- 531.2 nmol/mL in patients without history of catheter thrombosis (p = NS).
      CONCLUSION: Choline deficiency is a significant risk factor for development of
      catheter thrombosis in patients with intestinal failure who require PN.

PMID- 16804130
TI  - Age differences in fluid balance and serum Na+ and K+ levels after nasogastric
      tube feeding in stroke patients: elderly vs nonelderly.
AB  - BACKGROUND: Enteral nutrition support has been commonly used to improve nutrition
      status in acute stroke patients. The purpose of this study was to examine whether
      significant alterations in fluid and serum Na+ and K+ levels due to nasogastric
      tube feeding depended on patient age. METHODS: This study was conducted by
      retrospective review of the medical records of tube-fed patients with acute brain
      infarction who had been hospitalized in a university hospital. RESULTS: Rates of
      overhydration were high before tube feeding in both elderly and nonelderly stroke
      patients. This overhydration rate became more prevalent after iso-osmolal tube
      feeding in the elderly but decreased somewhat in the nonelderly subjects, and
      this difference in fluid balance after tube feeding between the elderly and
      nonelderly was statistically significant. Contrary to fluid balance, serum Na+
      and K+ concentrations were no different in the elderly and nonelderly patients
      after tube feeding. CONCLUSIONS: Although the results showed that overhydration
      state was prominent after tube feeding in the elderly, it appeared that there was
      a very mild clinical impact because the osmolality and serum sodium were not
      changed in this group. However, more attention to the maintenance of fluid
      balance in the elderly tube-fed stroke patients is needed because elderly
      patients have great difficulty in maintaining a normal fluid balance.

PMID- 16804131
TI  - Quantification of protein metabolism in vivo for skin, wound, and muscle in
      severe burn patients.
AB  - BACKGROUND: In response to injury, muscle catabolism can be extensive, and in
      theory, the wound consumes amino acids to support healing. The purpose of this
      study is to assess a technique by which in vivo protein kinetics of muscle,
      wound, and normal skin can be quantified in burn-injured patients. METHODS: Study
      protocol consisting of infusion of d5 phenylalanine; biopsies of skeletal muscle,
      skin, and donor-site wound on the leg; quantification of blood flow to total leg,
      wound, and skin; and sequential blood sampling from the femoral artery and vein.
      Five-compartment modeling was used to quantify the rates of protein synthesis,
      breakdown, and phenylalanine transport between muscle, wound, and skin. RESULTS:
      The study results demonstrated a net release of phenylalanine from muscle yet a
      net consumption of phenylalanine by the wound. Compared with skin, the wound had
      a substantially increased rate of protein synthesis and a reduced rate of protein
      breakdown (p < .01). Transport rates into and out of muscle were significantly
      higher than those for wound (p < .01). CONCLUSIONS: This novel methodology
      enables in vivo quantification of the integrated response of muscle, wound, and
      skin protein/amino acid metabolism and confirms the long-held theory of a net
      catabolism of muscle and a net anabolism of wound protein in patients after
      injury. This methodology can be used to assess the metabolic impact of such
      measures as nutrition, pharmacologic agents, and surgical procedures.

PMID- 16804132
TI  - Clinically relevant differences in accuracy of enteral nutrition feeding pump
      systems.
AB  - BACKGROUND: There are clinically relevant discrepancies between prescribed
      volumes and delivered volumes of enteral nutrition (EN) in intensive care unit
      (ICU) patients. Next to EN-protocol violations due to insufficient care, we
      hypothesized technical factors to be responsible for this deficit. The aim of
      this study was to determine the accuracy of EN feeding pump systems frequently
      used in the ICU. METHODS: Thirteen commercially available EN feeding pumps with
      their own delivery systems were tested in 12 sessions with different EN feeding
      tubes and EN formulas in a laboratory setting. The reproducibility of the
      measurements was determined for the 8 best performing EN feeding pump systems.
      RESULTS: There were clinically important differences between prescribed volumes
      and delivered volumes of EN in the tested EN feeding pump systems. The deficit in
      volume ranged from +66 mL (surplus of 66 mL) to -271 mL (deficit of 271 mL) per
      24 hours (14% of prescribed volume). Viscosity of test fluids (water/EN feeding
      formulas) and resistance of test tubes had no influence on the delivered volume
      by the tested EN feeding pump systems, because differences between prescribed
      volumes and delivered volumes were consistently found for each system while
      varying these test settings. CONCLUSIONS: Differences between prescribed and
      delivered EN volumes are caused by the function and construction of EN feeding
      pump systems. To improve nutrition therapy, the flow rate has to be adjusted or
      the best-performing EN feeding pump has to be purchased.

PMID- 16804137
TI  - The cover. Bridge at Moret-sur-Loing.

PMID- 16804134
TI  - New parenteral lipid emulsions for clinical use.
AB  - Routine use of parenteral lipid emulsions (LE) in clinical practice began in
      1961, with the development of soybean oil (SO) - based LE. Although clinically
      safe, experimental reports indicated that SO-based LE could exert a negative
      influence on immunological functions. Those findings were related to its absolute
      and relative excess of omega-6 polyunsaturated fatty acids (PUFA) and the low
      amount of omega-3 PUFA and also to its high PUFA content with an increased
      peroxidation risk. This motivated the development of new LE basically designed
      along the reduction of omega-6 PUFA and the omega-3 PUFA addition in order to
      obtain balanced levels of the omega-6/omega-3 ratio. The new LE for clinical use
      (available in Europe and South America) are differentiated by their content in
      polyunsaturated (omega-6 and omega-3), monounsaturated, and saturated fatty acids
      (FA), as well as FA source of their origin, including soy, coconut, olive, and
      fish oil. This article presents the new LE nutrition and energy functions but
      also its biochemical, metabolic, and immunomodulating aspects, according to their
      FA content. LE at 20% when infused from 1.0 to 2.0 g/kg body weight/day rates,
      either alone or in association with amino acids and glucose, are safe and well
      tolerated in routine clinical practice. LE combining SO with medium-chain
      triglycerides and/or olive oil have less omega-6 PUFA and are better metabolized,
      with less inflammatory and immunosuppressive effects than in relation to pure SO
      based LE. The omega-3 PUFA used alone or as component of a new and complex LE
      (soy, MCT, olive and fish oil) has demonstrated anti-inflammatory and
      immunomodulatory effects.

PMID- 16804133
TI  - The incidence and impact of dextrose dose on hyperglycemia from parenteral
      nutrition (PN) exposure in hematopoietic stem cell transplant (HSCT) recipients.
AB  - BACKGROUND: Short-term, transient hyperglycemia is associated with adverse
      outcomes in acutely ill populations. Because parenteral nutrition (PN) is
      dextrose based, we hypothesized that exposure to PN would be associated with
      hyperglycemia and that greater levels of dextrose infusion would be associated
      with higher glucose concentrations. Our objective was to examine the temporality,
      incidence, and dose response from dextrose load upon hyperglycemia using several
      serum glucose cut points in PN vs non-PN HSCT recipients. METHODS: The medical
      records of adults admitted for initial autologous or allogeneic hematopoietic
      stem cell transplant (HSCT) at 2 university-affiliated hospitals between
      September 1999 and December 2003 were used in this retrospective cohort. To
      minimize the impact of disease acuity on serum glucose, patients with diabetes
      mellitus, steroid administration, patients with recently treated infections, or
      patients who died during therapy were eliminated from the study. Serum glucose
      values were recorded once per day from the first morning venous blood draw (2 AM
      6 AM) to achieve uniformity among patients, to avoid measurements occurring more
      frequently among hyperglycemic patients, and to minimize the influence of oral
      intake. Hyperglycemia was examined using several serum glucose cut points (110,
      125, 150, 175, and 200 mg/dL). Wilcoxon rank-sum tests were used to detect
      differences in hyperglycemic events between PN and non-PN subjects, and mixed
      effects regression models were used to detect the association between PN exposure
      and hyperglycemia. To address the temporality and incidence of hyperglycemia
      between PN vs non-PN participants, before and "after" time frames were created.
      Preinfusion (before) and actual infusion (after) times were used for these
      intervals for PN patients; however, the average hospital days before (before) or
      during (after) PN infusion were used for comparison in non-PN recipients (ie,
      autologous non-PN before = hospital days 1-10, after = hospital days 11-21).
      RESULTS: Of the 208 patients who qualified for inclusion 49% (n = 101/208)
      received PN, which provided on average 26 kcal per kg, 1.3 g of protein per kg,
      and 2.7 mg/kg/min of dextrose (range 1.3-3.9 mg/kg/min). The proportion of
      hyperglycemic days before was not different between groups; however, it was
      significantly greater after in PN vs non-PN patients, regardless of serum glucose
      cut point. A dose response between dextrose administered (mg/kg/min) and serum
      glucose concentrations was not seen. When longitudinally presented, the temporal
      relationship between serum glucose and PN initiation was reflected approximately
      on hospital day 9. Using regression models that account for repeated measures,
      the odds of having hyperglycemia (yes/no; glucose >110 mg/dL) after PN exposure
      were nearly 4 times (odds ratio 3.9; 95% confidence interval, 2.7-5.5) that of
      non-PN exposed, after controlling for donor type, race, age, and conditioning
      chemotherapy. PN was the only variable to significantly interact with time (p <
      .0001), signifying not only the change in odds over time but also as powerful
      evidence that PN was the causative agent of hyperglycemic events. CONCLUSIONS:
      The broad use of PN at levels within current clinical guidelines in HSCT adults
      was associated with profound hyperglycemia; however, greater dextrose dose,
      within the narrow levels administered in this cohort, was not associated with
      higher glucose concentrations.

PMID- 16804138
TI  - A piece of my mind. The autopsy room.

PMID- 16804139
TI  - Reports of adverse events from bone drugs prompt caution.

PMID- 16804140
TI  - Rare disease research gets boost.

PMID- 16804141
TI  - Urinary catheter use often "inappropriate" in hospitalized elderly patients.

PMID- 16804142
TI  - Academic medical centers and conflicts of interest.

PMID- 16804143
TI  - Academic medical centers and conflicts of interest.

PMID- 16804144
TI  - Academic medical centers and conflicts of interest.

PMID- 16804145
TI  - Academic medical centers and conflicts of interest.

PMID- 16804146
TI  - Academic medical centers and conflicts of interest.

PMID- 16804147
TI  - Academic medical centers and conflicts of interest.

PMID- 16804148
TI  - Academic medical centers and conflicts of interest.

PMID- 16804149
TI  - Academic medical centers and conflicts of interest.

PMID- 16804150
TI  - Benefits vs the harms of automated external defibrillator use.

PMID- 16804151
TI  - Cognitive behavioral therapy vs zopiclone for treatment of chronic primary
      insomnia in older adults: a randomized controlled trial.
AB  - CONTEXT: Insomnia is a common condition in older adults and is associated with a
      number of adverse medical, social, and psychological consequences. Previous
      research has suggested beneficial outcomes of both psychological and
      pharmacological treatments, but blinded placebo-controlled trials comparing the
      effects of these treatments are lacking. OBJECTIVE: To examine short- and long
      term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological
      treatment in older adults experiencing chronic primary insomnia. DESIGN, SETTING,
      AND PARTICIPANTS: A randomized, double-blinded, placebo-controlled trial of 46
      adults (mean age, 60.8 y; 22 women) with chronic primary insomnia conducted
      between January 2004 and December 2005 in a single Norwegian university-based
      outpatient clinic for adults and elderly patients. INTERVENTION: CBT (sleep
      hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation;
      n = 18), sleep medication (7.5-mg zopiclone each night; n = 16), or placebo
      medication (n = 12). All treatment duration was 6 weeks, and the 2 active
      treatments were followed up at 6 months. MAIN OUTCOME MEASURES: Ambulant clinical
      polysomnographic data and sleep diaries were used to determine total wake time,
      total sleep time, sleep efficiency, and slow-wave sleep (only assessed using
      polysomnography) on all 3 assessment points. RESULTS: CBT resulted in improved
      short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome
      measures. For most outcomes, zopiclone did not differ from placebo. Participants
      receiving CBT improved their sleep efficiency from 81.4% at pretreatment to 90.1%
      at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the
      zopiclone group. Participants in the CBT group spent much more time in slow-wave
      sleep (stages 3 and 4) compared with those in other groups, and spent less time
      awake during the night. Total sleep time was similar in all 3 groups; at 6
      months, patients receiving CBT had better sleep efficiency using polysomnography
      than those taking zopiclone. CONCLUSION: These results suggest that interventions
      based on CBT are superior to zopiclone treatment both in short- and long-term
      management of insomnia in older adults. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00295386.

PMID- 16804152
TI  - Diurnal blood pressure pattern and risk of congestive heart failure.
AB  - CONTEXT: High blood pressure is the most important risk factor for congestive
      heart failure (CHF) at a population level, but the relationship of an altered
      diurnal blood pressure pattern to risk of subsequent CHF is unknown. OBJECTIVES:
      To explore 24-hour ambulatory blood pressure characteristics as predictors of CHF
      incidence and to investigate whether altered diurnal blood pressure patterns
      confer any additional risk information beyond that provided by conventional
      office blood pressure measurements. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective, community-based, observational cohort in Uppsala, Sweden, including
      951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy
      at baseline between 1990 and 1995, followed up until the end of 2002. Twenty-four
      hour ambulatory blood pressure monitoring was performed at baseline, and the
      blood pressure variables were analyzed as predictors of subsequent CHF. MAIN
      OUTCOME MEASURE: First hospitalization for CHF. RESULTS: Seventy men developed
      heart failure during follow-up, with an incidence rate of 8.6 per 1000 person
      years at risk. In multivariable Cox proportional hazards models adjusted for
      antihypertensive treatment and established risk factors for CHF (myocardial
      infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1
      SD (9-mm Hg) increase in nighttime ambulatory diastolic blood pressure (hazard
      ratio [HR], 1.26; 95% confidence interval [CI], 1.02-1.55) and the presence of
      "nondipping" blood pressure (night-day ambulatory blood pressure ratio > or =1;
      HR, 2.29; 95% CI, 1.16-4.52) were associated with an increased risk of CHF. After
      adjusting for office-measured systolic and diastolic blood pressures, nondipping
      blood pressure remained a significant predictor of CHF (HR, 2.21; 95% CI, 1.12
      4.36 vs normal night-day pattern). Nighttime ambulatory diastolic blood pressure
      and nondipping blood pressure were also significant predictors of CHF after
      exclusion of all participants who had an acute myocardial infarction before
      baseline or during follow-up. CONCLUSIONS: Nighttime blood pressure appears to
      convey additional risk information about CHF beyond office-measured blood
      pressure and other established risk factors for CHF. The clinical value of this
      association remains to be established in future studies.

PMID- 16804153
TI  - An outbreak of Fusarium keratitis associated with contact lens wear in Singapore.
AB  - CONTEXT: Fungal keratitis is a potentially blinding condition that is rarely seen
      with contact lens wear. OBJECTIVE: To describe a nationwide outbreak of fungal
      keratitis caused by Fusarium species among contact lens wearers in Singapore.
      DESIGN, SETTING, AND PATIENTS: Nationwide, hospital-based case series. All cases
      of fungal keratitis among contact lens wearers in all ophthalmology departments
      in Singapore were reviewed along with the charts of all contact lens wearers with
      culture-proven fungal keratitis from March 2005 through May 2006. A standardized
      telephone interview was conducted to obtain additional clinical information. MAIN
      OUTCOME MEASURE: Diagnosis of Fusarium keratitis associated with contact lens
      wear. RESULTS: During the study period, 66 patients (68 affected eyes) were
      diagnosed with Fusarium keratitis associated with contact lens wear; the
      estimated annual national incidence is 2.35 cases per 10,000 contact lens wearers
      (95% confidence interval, 0.62-7.22). Patients ranged in age from 13 to 44 years
      (mean [SD], 27.1 [8.4] years), of which 32 (48.5%) were men. The vast majority
      (65 patients; 98.5%) wore soft, disposable contact lenses; 62 patients (93.9%)
      reported using 1 brand of contact lens cleaning solution (ReNu, Bausch & Lomb,
      Rochester, NY), including 42 patients (63.6%) who recalled using ReNu with
      MoistureLoc. Most patients (81.8%) reported poor contact lens hygiene practices,
      including overnight use of daily wear contact lenses (19.7%), and use of contact
      lenses past the replacement date (43.9%). The final best-corrected visual acuity
      ranged from 20/20 to 20/80. Five patients (5 eyes; 7.4%) required emergency
      therapeutic or tectonic corneal transplantation. CONCLUSIONS: A new and evolving
      epidemic of Fusarium keratitis associated with contact lens wear was found in
      Singapore. Physicians and eye care practitioners worldwide need to be aware of
      the likelihood of similar outbreaks emerging among contact lens wearers.

PMID- 16804155
TI  - Compelled disclosure of health information: protecting against the greatest
      potential threat to privacy.

PMID- 16804156
TI  - Dr Osler's relapsing fever.

PMID- 16804154
TI  - Depression and cardiovascular disease: healing the broken-hearted.
AB  - Major depressive disorder is a risk factor for the development of incident
      coronary heart disease events in healthy patients and for adverse cardiovascular
      outcomes in patients with established heart disease. Depression is present in 1
      of 5 outpatients with coronary heart disease and in 1 of 3 outpatients with
      congestive heart failure, yet the majority of cases are not recognized or
      appropriately treated. It is not known whether treating depression improves
      cardiovascular outcomes, but antidepressant treatment with selective serotonin
      reuptake inhibitors is generally safe, alleviates depression, and improves
      quality of life. This article evaluates the importance of major depression in
      patients with cardiovascular disease, and provides practical guidance for
      identifying and treating this disorder.

PMID- 16804158
TI  - JAMA patient page. Insomnia.

PMID- 16804159
TI  - A high-throughput screening method to identify small molecule inhibitors of
      thyroid hormone receptor coactivator binding.
AB  - To provide alternative methods for regulation of gene transcription initiated by
      the binding of thyroid hormone (T3) to the thyroid receptor (TR), we have
      developed a high-throughput method for discovering inhibitors of the interaction
      of TR with its transcriptional coactivators. The screening method is based on
      fluorescence polarization (FP), one of the most sensitive and robust high
      throughput methods for the study of protein-protein interactions. A fluorescently
      labeled coactivator is excited by polarized light. The emitted polarized light is
      a function of the molecular properties of the labeled coactivator, especially
      Brownian molecular rotation, which is very sensitive to changes in the molecular
      mass of the labeled complex. Dissociation of hormone receptor from fluorescently
      labeled coactivator peptide in the presence of small molecules can be detected by
      this competition method, and the assay can be performed in a high-throughput
      screening format. Hit compounds identified by this method are evaluated by
      several secondary assay methods, including a dose-response analysis, a
      semiquantitative glutathione-S-transferase assay, and a hormone displacement
      assay. Subsequent in vitro transcription assays can detect inhibition of thyroid
      signaling at low micromolar concentrations of small molecules in the presence of
      T3.

PMID- 16804160
TI  - A previously unidentified activity of yeast and mouse RNA:pseudouridine synthases
      1 (Pus1p) on tRNAs.
AB  - Mouse pseudouridine synthase 1 (mPus1p) was the first vertebrate
      RNA:pseudouridine synthase that was cloned and characterized biochemically. The
      mPus1p was previously found to catalyze Psi formation at positions 27, 28, 34,
      and 36 in in vitro produced yeast and human tRNAs. On the other hand, the
      homologous Saccharomyces cerevisiae scPus1p protein was shown to modify seven
      uridine residues in tRNAs (26, 27, 28, 34, 36, 65, and 67) and U44 in U2 snRNA.
      In this work, we expressed mPus1p in yeast cells lacking scPus1p and studied
      modification of U2 snRNA and several yeast tRNAs. Our data showed that, in these
      in vivo conditions, the mouse enzyme efficiently modifies yeast U2 snRNA at
      position 44 and tRNAs at positions 27, 28, 34, and 36. However, a tRNA:Psi26
      synthase activity of mPus1p was not observed. Furthermore, we found that both
      scPus1p and mPus1p, in vivo and in vitro, have a previously unidentified activity
      at position 1 in cytoplasmic tRNAArg(ACG). This modification can take place in
      mature tRNA, as well as in pre-tRNAs with 5' and/or 3' extensions. Thus, we
      identified the protein carrying one of the last missing yeast tRNA:Psi synthase
      activities. In addition, our results reveal an additional activity of mPus1p at
      position 30 in tRNA that scPus1p does not possess.

PMID- 16804161
TI  - Regulation of poly(A) binding protein function in translation: Characterization
      of the Paip2 homolog, Paip2B.
AB  - The 5' cap and 3' poly(A) tail of eukaryotic mRNAs act synergistically to enhance
      translation. This synergy is mediated via interactions between eIF4G (a component
      of the eIF4F cap binding complex) and poly(A) binding protein (PABP). Paip2 (PABP
      interacting protein 2) binds PABP and inhibits translation both in vitro and in
      vivo by decreasing the affinity of PABP for polyadenylated RNA. Here, we describe
      the functional characteristics of Paip2B, a Paip2 homolog. A full-length brain
      cDNA of Paip2B encodes a protein that shares 59% identity and 80% similarity with
      Paip2 (Paip2A), with the highest conservation in the two PABP binding domains.
      Paip2B acts in a manner similar to Paip2A to inhibit translation of capped and
      polyadenylated mRNAs both in vitro and in vivo by displacing PABP from the
      poly(A) tail. Also, similar to Paip2A, Paip2B does not affect the translation
      mediated by the internal ribosome entry site (IRES) of hepatitis C virus (HCV).
      However, Paip2A and Paip2B differ with respect to both mRNA and protein
      distribution in different tissues and cell lines. Paip2A is more highly
      ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome.
      Paip2 protein degradation may constitute a primary mechanism by which cells
      regulate PABP activity in translation.

PMID- 16804162
TI  - Quantitative profiling of the membrane proteome in a halophilic archaeon.
AB  - We present a large scale quantitation study of the membrane proteome from
      Halobacterium salinarum. To overcome problems generally encountered with membrane
      proteins, we established a membrane preparation protocol that allows the
      application of most proteomic techniques originally developed for soluble
      proteins. Proteins were quantified using two complementary approaches. For gel
      based quantitation, DIGE labeling was combined with two-dimensional gel
      electrophoresis on an improved 16-benzyldimethyl-n-hexadecylammonium chloride/SDS
      system. MS-based quantitation was carried out by combining gel-free separation
      with the recently developed isotope-coded protein labeling technique. Good
      correlations between these two independent quantitation strategies were obtained.
      From computational analysis we conclude that labeling of free amino groups by
      isotope-coded protein labeling (Lys and free N termini) is better suited for
      membrane proteins than Cys-based labeling strategies but that quantitation of
      integral membrane proteins remains cumbersome compared with soluble proteins.
      Nevertheless we could quantify 155 membrane proteins; 101 of these had
      transmembrane domains. We compared two growth states that strongly affect the
      energy supply of the cells: aerobic versus anaerobic/phototrophic conditions. The
      photosynthetic protein bacteriorhodopsin is the most highly regulated protein. As
      expected, several other membrane proteins involved in aerobic or anaerobic energy
      metabolism were found to be regulated, but in total, however, the number of
      regulated proteins is rather small.

PMID- 16804163
TI  - On the enhancement of anti-neurotoxin antibody production by subcomponents HA1
      and HA3b of Clostridium botulinum type B 16S toxin-haemagglutinin.

PMID- 16804164
TI  - One size doesn't fit all.

PMID- 16804166
TI  - Metabolic and regulatory engineering of Serratia marcescens: mimicking phage
      mediated horizontal acquisition of antibiotic biosynthesis and quorum-sensing
      capacities.
AB  - Serratia marcescens is an important cause of opportunistic human infections.
      Many, but not all, strains produce prodigiosin, a secondary metabolic, red
      pigment antibiotic, the biosynthesis of which is directed by the pig gene
      cluster. Quorum sensing (QS) involves the production and detection of chemical
      signal molecules as a means to regulate gene expression in response to population
      cell density. Several strains of S. marcescens have previously been shown to
      possess an N-acyl-L-homoserine lactone (aHSL) QS system. This study aimed to
      determine the impact of introducing, by phage-mediated horizontal gene transfer,
      a biosynthetic gene cluster (pig) and a regulatory locus (aHSL QS) into strains
      lacking the respective trait. The pig cluster from S. marcescens ATCC 274 (Sma
      274) was transferred to the non-pigmented strain, S. marcescens strain 12 (Sma
      12). In the engineered strain, pigment was expressed and brought under the
      control of the recipient's native regulatory systems (aHSL QS and luxS).
      Moreover, transfer of the aHSL locus from Sma 12 to the non-QS Sma 274 resulted
      in the imposition of aHSL control onto a variety of native traits, including
      pigment production. In addition, during this study, the QS regulon of the
      clinical strain, Sma 12, was characterized, and some novel QS-regulated traits in
      S. marcescens were identified. The results have implications for the evolution
      and dissemination of biosynthetic and QS loci, illustrating the genetic
      modularity and ease of acquisition of these traits and the capacity of phages to
      act as vectors for horizontal gene transfer.

PMID- 16804167
TI  - Broad-spectrum antibacterial activity by a novel abiogenic peptide mimic.
AB  - The human-mediated use and abuse of classical antibiotics has created a strong
      selective pressure for the rapid evolution of antibiotic resistance. As
      resistance levels rise, and the efficacy of classical antibiotics wanes, the
      intensity of the search for alternative antimicrobials has increased. One class
      of molecules that has attracted much attention is the antimicrobial peptides
      (AMPs). They exhibit broad-spectrum activity, they are potent and they are
      widespread as part of the innate defence system of both vertebrates and
      invertebrates. However, peptides are complex molecules that suffer from
      proteolytic degradation. The ability to capture the essential properties of
      antimicrobial peptides in simple easy-to-prepare molecules that are abiotic in
      origin and non-proteolytic offers many advantages. Mechanistic and structural
      knowledge of existing AMPs was used to design a novel compound that mimics the
      biochemical activity of an AMP. This report describes the development and in
      vitro characterization of a small peptide mimic that exhibited quick-acting and
      selective antibacterial activity against a broad range of bacteria, including
      numerous clinically relevant strains, at low MIC values.

PMID- 16804168
TI  - Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial
      germination, antifungal resistance and hypervirulence.
AB  - The ECM33/SPS2 family of glycosylphosphatidylinositol-anchored proteins plays an
      important role in maintaining fungal cell wall integrity and virulence. However,
      the precise molecular role of these proteins is unknown. In this work, AfuEcm33,
      the gene encoding the ECM33 homologue in the important pathogenic fungus
      Aspergillus fumigatus, has been cloned and its function analysed. It is shown
      that disruption of AfuEcm33 results in rapid conidial germination, increased cell
      cell adhesion, resistance to the antifungal agent caspofungin and increased
      virulence in an immunocompromised mouse model for disseminated aspergillosis.
      These results suggest that the protein encoded by AfuEcm33 is involved in key
      aspects of cell wall morphogenesis and plays an important role in A. fumigatus
      virulence.

PMID- 16804169
TI  - Identification and functional analysis of the genes for naphthalenesulfonate
      catabolism by Sphingomonas xenophaga BN6.
AB  - Sphingomonas xenophaga BN6 degrades various (substituted) naphthalenesulfonates
      to the corresponding (substituted) salicylates. A gene cluster was identified on
      the plasmid pBN6 which coded for several enzymes participating in the degradative
      pathway for naphthalenesulfonates. A DNA fragment of 16 915 bp was sequenced
      which contained 17 ORFs. The genes encoding the 1,2-dihydroxynaphthalene
      dioxygenase, 2-hydroxychromene-2-carboxylate isomerase, and 2'
      hydroxybenzalpyruvate aldolase of the naphthalenesulfonate pathway were
      identified on the DNA fragment and the encoded proteins heterologously expressed
      in Escherichia coli. Also, the genes encoding the ferredoxin and ferredoxin
      reductase of a multi-component, ring-hydroxylating naphthalenesulfonate
      dioxygenase were identified by insertional inactivation. The identified genes
      generally demonstrated the highest degree of homology to enzymes encoded by the
      phenanthrene-degrading organism Sphingomonas sp. P2, or the megaplasmid pNL1 of
      the naphthalene- and biphenyl-degrading strain Sphingomonas aromaticivorans F199.
      The genes of S. xenophaga BN6 participating in the degradation of
      naphthalenesulfonates also shared the same organization in three different
      transcriptional units as the genes involved in the degradation of naphthalene,
      biphenyl, and phenanthrene previously found in Sphingomonas sp. P2 and S.
      aromaticivorans F199. The genes were flanked in S. xenophaga BN6 by ORFs which
      specify proteins that show the highest homologies to proteins of mobile genetic
      elements.

PMID- 16804170
TI  - Cloning and expression of the gene for periplasmic poly(vinyl alcohol)
      dehydrogenase from Sphingomonas sp. strain 113P3, a novel-type quinohaemoprotein
      alcohol dehydrogenase.
AB  - A gene for periplasmic poly(vinyl alcohol) (PVA) dehydrogenase (PVADH) was
      cloned, based on the N-terminal amino acid sequence of the purified PVADH from
      Sphingomonas sp. 113P3 and the sequence of the gene for PVADH (pvaA, GenBank
      accession no. AB190288). The recombinant PVADH tagged with hexahistidine was
      expressed in Escherichia coli and purified to homogeneity. The recombinant enzyme
      had the same characteristics as the purified enzyme from Sphingomonas sp. strain
      113P. In addition to PVA, the recombinant PVADH could oxidize glycols such as
      polypropylene glycols and 1,3-butane/cyclohexanediol and 2,4-pentanediol, but
      neither primary nor secondary alcohols. The amino acid sequence of the
      recombinant PVADH showed similarity with those of PVADH from Pseudomonas sp.
      strain VM15C, putative PVADHs from Azoarcus sp. EbN1, and Xanthomonas species (54
      25 % identity), and the quinohaemoprotein alcohol dehydrogenases (QH-ADHs) from
      Comamonas testosteroni, Ralstonia eutropha and Pseudomonas putida (25-29 %
      identity). PVADHs from strains 113P3 and VM15C have a conserved superbarrel
      domain (SD), probable PQQ-binding amino acids in the SD and a haem-binding domain
      (HBD) (they should be designated QH-PVADHs), but the positions of the amino acid
      sequences for the HBD and SD are the reverse of those of QH-ADHs. A protein
      structure of QH-PVADHs is proposed. Results of dot-blot hybridization and RT-PCR
      indicated that the three genes encoding oxidized PVA hydrolase, PVADH and
      cytochrome c are expressed constitutively and form an operon.

PMID- 16804171
TI  - Two novel conjugative plasmids from a single strain of Sulfolobus.
AB  - Two conjugative plasmids (CPs) were isolated and characterized from the same
      'Sulfolobus islandicus' strain, SOG2/4. The plasmids were separated from each
      other and transferred into Sulfolobus solfataricus. One has a high copy number
      and is not stable (pSOG1) whereas the other has a low copy number and is stably
      maintained (pSOG2). Plasmid pSOG2 is the first Sulfolobus CP found to have these
      characteristics. The genomes of both pSOG plasmids have been sequenced and were
      compared to each other and the available Sulfolobus CPs. Interestingly, apart
      from a very well-conserved core, 70 % of the pSOG1 and pSOG2 genomes is largely
      different and composed of a mixture of genes that often resemble counterparts in
      previously described Sulfolobus CPs. However, about 20 % of the predicted genes
      do not have known homologues, not even in other CPs. Unlike pSOG1, pSOG2 does not
      contain a gene for the highly conserved PlrA protein nor for obvious homologues
      of partitioning proteins. Unlike pNOB8 and pKEF9, both pSOG plasmids lack the so
      called clustered regularly interspaced short palindrome repeats (CRISPRs). The
      sites of recombination between the two genomes can be explained by the presence
      of recombination motifs previously identified in other Sulfolobus CPs. Like other
      Sulfolobus CPs, the pSOG plasmids possess a gene encoding an integrase of the
      tyrosine recombinase family. This integrase probably mediates plasmid site
      specific integration into the host chromosome at the highly conserved tRNA(Glu)
      loci.

PMID- 16804172
TI  - Molecular characterization of a conserved archaeal copper resistance (cop) gene
      cluster and its copper-responsive regulator in Sulfolobus solfataricus P2.
AB  - Using a comparative genomics approach, a copper resistance gene cluster has been
      identified in multiple archaeal genomes. The cop cluster is predicted to encode a
      metallochaperone (CopM), a P-type copper-exporting ATPase (CopA) and a novel,
      archaea-specific transcriptional regulator (CopT) which might control the
      expression of the cop genes. Sequence analysis revealed that CopT has an N
      terminal DNA-binding helix-turn-helix domain and a C-terminal TRASH domain; TRASH
      is a novel domain which has recently been proposed to be uniquely involved in
      metal-binding in sensors, transporters and trafficking proteins in prokaryotes.
      The present study describes the molecular characterization of the cop gene
      cluster in the thermoacidophilic crenarchaeon Sulfolobus solfataricus. The
      polycistronic copMA transcript was found to accumulate in response to growth
      inhibiting copper concentrations, whereas copT transcript abundance appeared to
      be constitutive. DNA-binding assays revealed that CopT binds to the copMA
      promoter at multiple sites, both upstream and downstream of the predicted TATA
      BRE site. Copper was found to specifically modulate the affinity of DNA binding
      by CopT. This study describes a copper-responsive operon in archaea, a new family
      of archaeal DNA-binding proteins, and supports the idea that this domain plays a
      prominent role in the archaeal copper response. A model is proposed for copper
      responsive transcriptional regulation of the copMA gene cluster.

PMID- 16804173
TI  - Expression of the Giardia lamblia cyst wall protein 2 in Lactococcus lactis.
AB  - In this study, Lactococcus lactis was engineered to express Giardia lamblia cyst
      wall protein 2 (CWP2) at three different subcellular locations, intracellular,
      secreted or cell-surface-anchored, using nisin as an inducing agent. CWP2
      expression did not appear to be detrimental to L. lactis viability. No particular
      subcellular location of CWP2 expression offered any advantages over the others
      with respect to decreased toxicity towards the bacteria. All recombinant
      lactococci experienced a similar reduction in growth rate when induced. It was
      determined whether recombinant lactococcal cells engineered for cell surface
      expression of CWP2 were capable of inducing a CWP2-specific mucosal IgA antibody
      response. Recombinant lactococci were successful at inducing CWP2-specific IgA
      antibodies. Moreover, in a pilot challenge experiment, mice immunized with these
      recombinant lactococci demonstrated a significant (63 %) reduction in cyst
      output. Thus, it has been demonstrated that G. lamblia CWP2 may be expressed in
      L. lactis and that recombinant lactococcal cells elicit Giardia-specific
      antibodies which reduce cyst shedding in a murine model.

PMID- 16804174
TI  - Dysgalacticin: a novel, plasmid-encoded antimicrobial protein (bacteriocin)
      produced by Streptococcus dysgalactiae subsp. equisimilis.
AB  - Dysgalacticin is a novel bacteriocin produced by Streptococcus dysgalactiae
      subsp. equisimilis strain W2580 that has a narrow spectrum of antimicrobial
      activity directed primarily against the principal human streptococcal pathogen
      Streptococcus pyogenes. Unlike many previously described bacteriocins of Gram
      positive bacteria, dysgalacticin is a heat-labile 21.5 kDa anionic protein that
      kills its target without inducing lysis. The N-terminal amino acid sequence of
      dysgalacticin [Asn-Glu-Thr-Asn-Asn-Phe-Ala-Glu-Thr-Gln-Lys-Glu-Ile-Thr-Thr-Asn
      (Asn)-Glu-Ala] has no known homologue in publicly available sequence databases.
      The dysgalacticin structural gene, dysA, is located on the indigenous plasmid
      pW2580 of strain W2580 and encodes a 220 aa preprotein which is probably exported
      via a Sec-dependent transport system. Natural dysA variants containing
      conservative amino acid substitutions were also detected by sequence analyses of
      dysA elements from S. dysgalactiae strains displaying W2580-like inhibitory
      profiles. Production of recombinant dysgalacticin by Escherichia coli confirmed
      that this protein is solely responsible for the inhibitory activity exhibited by
      strain W2580. A combination of in silico secondary structure prediction and
      reductive alkylation was employed to demonstrate that dysgalacticin has a novel
      structure containing a disulphide bond essential for its biological activity.
      Moreover, dysgalacticin displays similarity in predicted secondary structure (but
      not primary amino acid sequence or inhibitory spectrum) with another plasmid
      encoded streptococcal bacteriocin, streptococcin A-M57 from S. pyogenes,
      indicating that dysgalacticin represents a prototype of a new class of
      antimicrobial proteins.

PMID- 16804175
TI  - A screening system for carbon sources enhancing beta-N-acetylglucosaminidase
      formation in Hypocrea atroviridis (Trichoderma atroviride).
AB  - To identify carbon sources that trigger beta-N-acetylglucosaminidase (NAGase)
      formation in Hypocrea atroviridis (anamorph Trichoderma atroviride), a screening
      system was designed that consists of a combination of Biolog Phenotype MicroArray
      plates, which contain 95 different carbon sources, and specific enzyme activity
      measurements using a chromogenic substrate. The results revealed growth-dependent
      kinetics of NAGase formation and it was shown that NAGase activities were
      enhanced on carbon sources sharing certain structural properties, especially on
      alpha-glucans (e.g. glycogen, dextrin and maltotriose) and oligosaccharides
      containing galactose. Enzyme activities were assessed in the wild-type and a H.
      atroviridis Deltanag1 strain to investigate the influence of the two NAGases,
      Nag1 and Nag2, on total NAGase activity. Reduction of NAGase levels in the
      Deltanag1 strain in comparison to the wild-type was strongly carbon-source and
      growth-phase dependent, indicating the distinct physiological roles of the two
      proteins. The transcript abundance of nag1 and nag2 was increased on carbon
      sources with elevated NAGase activity, indicating transcriptional regulation of
      these genes. The screening method for the identification of carbon sources that
      induce enzymes or a gene of interest, as presented in this paper, can be adapted
      for other purposes if appropriate enzyme or reporter assays are available.

PMID- 16804176
TI  - Methylglyoxal detoxification by an aldo-keto reductase in the cyanobacterium
      Synechococcus sp. PCC 7002.
AB  - Aldo-keto reductases (AKRs) are a superfamily of enzymes that reduce aldehydes
      and ketones, and have a broad range of substrates. An AKR gene, sakR1, was
      identified in the cyanobacterium Synechococcus sp. PCC 7002. A mutant strain with
      sakR1 inactivated was sensitive to glycerol, a carbon source that can support
      heterotrophic growth of Synechococcus sp. PCC 7002. It was found that the sakR1
      null mutant accumulated more toxic methylglyoxal than the wild-type when glycerol
      was added to growth medium, suggesting that SakR1 is involved in the
      detoxification of methylglyoxal, a highly toxic metabolite that can damage
      cellular macromolecules. Enzymic analysis of recombinant SakR1 protein showed
      that it can efficiently reduce methylglyoxal with NADPH. Based on immunoblotting,
      SakR1 was not upregulated at an increased cellular methylglyoxal concentration. A
      pH-dependent enzyme-activity profile suggested that SakR1 activity could be
      regulated by cellular pH in Synechococcus sp. PCC 7002. The broad substrate
      specificity of SakR1 implies that SakR1 could play other roles in cellular
      metabolism.

PMID- 16804177
TI  - Osmotic stress in Synechocystis sp. PCC 6803: low tolerance towards nonionic
      osmotic stress results from lacking activation of glucosylglycerol accumulation.
AB  - In order to compare the molecular principles of the acclimatization of bacterial
      cells to salt and nonionic osmotic stress, the moderately halotolerant
      cyanobacterium Synechocystis sp. PCC 6803 was challenged by salt (NaCl), and the
      osmolytes sorbitol and maltose. The physiological response towards each of the
      three compounds was found to be different. After salt addition, the cell volume
      remained unchanged, and the accumulation of the osmoprotective compound
      glucosylglycerol (GG) was observed after activation of the key enzyme GgpS at the
      biochemical and gene (ggpS) expression level. Sorbitol addition had only minor
      effects on the cell volume. In spite of the fact that the ggpS expression was
      increased, the GgpS enzyme was not activated, resulting in the absence of GG
      accumulation. In contrast the cells accumulated sorbitol, which served as a
      compatible solute and assured a certain osmotic resistance. In comparison to NaCl
      and sorbitol, the addition of maltose caused a strong decrease in cell volume
      indicating water efflux. However, no osmolyte accumulation was observed,
      resulting in an osmosensitive phenotype. Consequently, a successful response of
      Synechocystis cells to an osmotic challenge is indicative of the de novo
      synthesis of GG upon salt-dependent activation of the GgpS enzyme or the uptake
      of external solutes.

PMID- 16804178
TI  - Candida albicans SNO1 and SNZ1 expressed in stationary-phase planktonic yeast
      cells and base of biofilm.
AB  - The Candida albicans homologues of the most studied Saccharomyces cerevisiae
      stationary-phase genes, SNO1 and SNZ1, were used to test the hypothesis that,
      within a biofilm, some cells reach stationary phase within continuously fed, as
      well as static, C. albicans biofilms grown on dental acrylic. The authors first
      studied the expression patterns of these two genes in planktonic growth
      conditions. Using real-time RT-PCR (RT-RTPCR), increased peak expression of both
      SNZ1 and SNO1 was observed at 5 and 6 days, respectively, in C. albicans grown in
      suspension culture. SNZ1-yellow fluorescent protein (YFP) and SNO1-YFP were
      constructed to study expression at the cellular level and protein localization in
      C. albicans. Snz1p-YFP and Sno1p-YFP localized to the cytoplasm with maximum
      expression (>90 %) at 5 and 6 days, respectively, in planktonic conditions. When
      yeast growth was reinitiated, loss of fluorescence began immediately. Germ tubes
      and hyphae were non-fluorescent. Pseudohyphae began appearing at 9 days in
      planktonic yeast culture and expressed each protein by 11 days; however, the
      cells budding from pseudohyphae were not fluorescent. Biofilm was formed in vitro
      under either static or continuously fed conditions. Increased expression of the
      two genes was shown by RT-RTPCR, beginning by day 3 and increasing through to day
      15 (continuously fed biofilm). Only the bottommost layer of acrylic-adhered cells
      in the biofilm showed 25 and 40 % fluorescence at 6 and 15 days, respectively.
      These observations suggest that only a few cells in C. albicans biofilms express
      genes associated with the planktonic stationary phase and that these are found at
      the bottom of the biofilm adhered to the surface.

PMID- 16804179
TI  - Antimicrobial activity of potato aspartic proteases (StAPs) involves membrane
      permeabilization.
AB  - Solanum tuberosum aspartic proteases (StAPs) with antimicrobial activity are
      induced after abiotic and biotic stress. In this study the ability of StAPs to
      produce a direct antimicrobial effect was investigated. Viability assays
      demonstrated that StAPs are able to kill spores of Fusarium solani and
      Phytophthora infestans in a dose-dependent manner. Localization experiments with
      FITC-labelled StAPs proved that the proteins interact directly with the surface
      of spores and hyphae of F. solani and P. infestans. Moreover, incubation of
      spores and hyphae with StAPs resulted in membrane permeabilization, as shown by
      the uptake of the fluorescent dye SYTOX Green. It is concluded that the
      antimicrobial effect of StAPs against F. solani and P. infestans is caused by a
      direct interaction with the microbial surfaces followed by membrane
      permeabilization.

PMID- 16804180
TI  - Isolation of salt-sensitive mutants of Sinorhizobium meliloti strain Rm1021.
AB  - The determinants necessary for adaptation to high NaCl concentrations and
      competition for nodule occupancy in Sinorhizobium meliloti were investigated
      genetically. Mutations in fabG as well as smc02909 (transmembrane
      transglycosylase), trigger factor (tig) and smc00717 (probably ftsE) gave rise to
      strains that were unable to tolerate high salt and were uncompetitive for nodule
      occupancy relative to the wild-type. Moreover exoF1, exoA and pgm determinants
      were determined to be necessary for strain Rm1021 to survive high NaCl and/or
      MgCl(2) concentrations. The introduction of an expR(+) allele was capable of
      suppressing the Mg(2+) sensitivity associated with the exoF1, but not the exoA,
      mutation in a manner independent of exopolysaccharide II (EPS II)-associated
      mucoidy. The results also show that the EPS II-associated mucoid phenotype was
      affected by either Mg(2+)or K(+), but not by Li(+), Ca(2+), or high osmolarity.

PMID- 16804181
TI  - Characterization of genes involved in erythritol catabolism in Rhizobium
      leguminosarum bv. viciae.
AB  - A genetic locus encoding erythritol uptake and catabolism genes was identified in
      Rhizobium leguminosarum bv. viciae, and shown to be plasmid encoded in a wide
      range of R. leguminosarum strains. A Tn5-B22 mutant (19B-3) unable to grow on
      erythritol was isolated from a mutant library of R. leguminosarum strain VF39SM.
      The mutated gene eryF was cloned and partially sequenced, and determined to have
      a high homology to permease genes of ABC transporters. A cosmid complementing the
      mutation (pCos42) was identified and was shown to carry all the genes necessary
      to restore the ability to grow on erythritol to a VF39SM strain cured of
      pRleVF39f. In the genomic DNA sequence of strain 3841, the gene linked to the
      mutation in 19B-3 is flanked by a cluster of genes with high homology to the
      known erythritol catabolic genes from Brucella spp. Through mutagenesis studies,
      three distinct operons on pCos42 that are required for growth on erythritol were
      identified: an ABC-transporter operon (eryEFG), a catabolic operon (eryABCD) and
      an operon (deoR-tpiA2-rpiB) that encodes a gene with significant homology to
      triosephosphate isomerase (tpiA2). These genes all share high sequence identity
      to genes in the erythritol catabolism region of Brucella spp., and clustalw
      alignments suggest that horizontal transfer of the erythritol locus may have
      occurred between R. leguminosarum and Brucella. Transcription of the eryABCD
      operon is repressed by EryD and is induced by the presence of erythritol. Mutant
      19B-3 was impaired in its ability to compete against wild-type for nodulation of
      pea plants but was still capable of forming nitrogen-fixing nodules.

PMID- 16804182
TI  - Effect of AmtB homologues on the post-translational regulation of nitrogenase
      activity in response to ammonium and energy signals in Rhodospirillum rubrum.
AB  - The AmtB protein transports uncharged NH(3) into the cell, but it also interacts
      with the nitrogen regulatory protein P(II), which in turn regulates a variety of
      proteins involved in nitrogen fixation and utilization. Three P(II) homologues,
      GlnB, GlnK and GlnJ, have been identified in the photosynthetic bacterium
      Rhodospirillum rubrum, and they have roles in at least four overlapping and
      distinct functions, one of which is the post-translational regulation of
      nitrogenase activity. In R. rubrum, nitrogenase activity is tightly regulated in
      response to addition or energy depletion (shift to darkness), and this regulation
      is catalysed by the post-translational regulatory system encoded by draTG. Two
      amtB homologues, amtB(1) and amtB(2), have been identified in R. rubrum, and they
      are linked with glnJ and glnK, respectively. Mutants lacking AmtB(1) are
      defective in their response to both addition and darkness, while mutants lacking
      AmtB(2) show little effect on the regulation of nitrogenase activity. These
      responses to darkness and appear to involve different signal transduction
      pathways, and the poor response to darkness does not seem to be an indirect
      result of perturbation of internal pools of nitrogen. It is also shown that
      AmtB(1) is necessary to sequester detectable amounts GlnJ to the cell membrane.
      These results suggest that some element of the AmtB(1)-P(II) regulatory system
      senses energy deprivation and a consistent model for the integration of nitrogen,
      carbon and energy signals by P(II) is proposed. Other results demonstrate a
      degree of specificity in interaction of AmtB(1) with the different P(II)
      homologues in R. rubrum. Such interaction specificity might be important in
      explaining the way in which P(II) proteins regulate processes involved in
      nitrogen acquisition and utilization.

PMID- 16804183
TI  - Role of the Escherichia coli nitrate transport protein, NarU, in survival during
      severe nutrient starvation and slow growth.
AB  - Escherichia coli K-12 strains expressing either NarU or NarK as the only nitrate
      transport protein are both able to support nitrate-dependent anaerobic growth.
      The narK gene is highly expressed during anaerobic growth in the presence of
      nitrate, consistent with a role for NarK in nitrate transport coupled to nitrate
      reduction by the most active nitrate reductase encoded by the adjacent narGHJI
      operon. The physiological role of NarU is unknown. Reverse transcriptase PCR
      experiments established that, unlike the monocistronic narK gene, narU is co
      transcribed with narZ as the first gene of a five-gene narUZYWV operon. The narK
      and narU genes were fused in-frame to a myc tag: the encoded fusion proteins
      complemented the nitrate-dependent growth defect of chromosomal narK and narU
      mutations. A commercial anti-Myc antibody was used to detect NarK and NarU in
      membrane fractions. During anaerobic growth in the presence of nitrate, the
      quantity of NarU-Myc accumulated during exponential growth was far less than that
      of NarK-Myc, but NarU was more abundant than NarK in stationary-phase cultures in
      the absence of nitrate. Although the concentration of NarU-Myc increased
      considerably during the post-exponential phase of growth, NarK-Myc was still more
      abundant than NarU-Myc in stationary-phase bacteria in the presence of nitrate.
      In chemostat competition experiments, a strain expressing only narU had a
      selective advantage relative to a strain expressing only narK during nutrient
      starvation or very slow growth, but NarK(+) bacteria had a much greater selective
      advantage during rapid growth. The data suggest that NarU confers a selective
      advantage during severe nutrient starvation or slow growth, conditions similar to
      those encountered in vivo.

PMID- 16804184
TI  - Antigen-43-mediated autoaggregation impairs motility in Escherichia coli.
AB  - Functional interaction between bacterial surface-displayed autoaggregation
      proteins such as antigen 43 (Ag43) of Escherichia coli and motility organelles
      such as flagella has not previously been described. Here, it has been
      demonstrated for the first time that Ag43-mediated aggregation can inhibit
      bacterial motility. Ag43 overexpression produces a dominant aggregation phenotype
      that overrides motility in the presence of low levels of flagella. In contrast,
      induction of an increased flagellation state prevents Ag43-mediated aggregation.
      This phenomenon was observed in naturally occurring subpopulations of E. coli as
      phase variants expressing and not expressing Ag43 revealed contrasting motility
      phenotypes. The effects were shown to be part of a general mechanism because
      other short adhesins capable of mediating autoaggregation (AIDA-I and TibA) also
      impaired motility. These novel insights into the function of bacterial
      autoaggregation proteins suggest that a balance between these two systems, i.e.
      autoaggregation and flagellation, influences motility.

PMID- 16804185
TI  - Global gene expression in Escherichia coli K-12 during short-term and long-term
      adaptation to glucose-limited continuous culture conditions.
AB  - Microarray technology was used to study the cellular events that take place at
      the transcription level during short-term (physiological) and long-term (genetic)
      adaptation of the faecal indicator bacterium Escherichia coli K-12 to slow growth
      under limited nutrient supply. Short-term and long-term adaptation were assessed
      by comparing the mRNA levels isolated after 40 or 500 h of glucose-limited
      continuous culture at a dilution rate of 0.3 h(-1) with those from batch culture
      with glucose excess. A large number of genes encoding periplasmic binding
      proteins were upregulated, indicating that the cells are prepared for high
      affinity uptake of all types of carbon sources during glucose-limited growth in
      continuous culture. All the genes belonging to the maltose (mal/lamB) and
      galactose (mgl/gal) operons were upregulated. A similar transcription pattern was
      observed for long-term cultures except that the expression factors were lower
      than in the short-term adaptation. The patterns of upregulation were confirmed by
      real-time RT-PCR. A switch from a fully operational citric acid cycle to the PEP
      glyoxylate cycle was clearly observed in cells grown in glucose-limited
      continuous culture when compared to batch-grown cells and this was confirmed by
      transcriptome analysis. This transcriptome analysis confirms and extends the
      observations from previous proteome and catabolome studies in the authors'
      laboratory.

PMID- 16804186
TI  - Functional identification of ygiP as a positive regulator of the ttdA-ttdB-ygjE
      operon.
AB  - Functional characterization of unknown genes is currently a major task in
      biology. The search for gene function involves a combination of various in
      silico, in vitro and in vivo approaches. Available knowledge from the study of
      more than 21 LysR-type regulators in Escherichia coli has facilitated the
      classification of new members of the family. From sequence similarities and its
      location on the E. coli chromosome, it is suggested that ygiP encodes a lysR
      regulator controlling the expression of a neighbouring operon; this operon
      encodes the two subunits of tartrate dehydratase (TtdA, TtdB) and YgiE, an
      integral inner-membrane protein possibly involved in tartrate uptake. Expression
      of tartrate dehydratase, which converts tartrate to oxaloacetate, is required for
      anaerobic growth on glycerol as carbon source in the presence of tartrate. Here,
      it has been demonstrated that disruption of ygiP, ttdA or ygjE abolishes tartrate
      dependent anaerobic growth on glycerol. It has also been shown that tartrate
      dependent induction of the ttdA-ttdB-ygjE operon requires a functional YgiP.

PMID- 16804187
TI  - Distribution of prophages and SGI-1 antibiotic-resistance genes among different
      Salmonella enterica serovar Typhimurium isolates.
AB  - Recently, the authors identified Salmonella enterica serovar Typhimurium (S.
      Typhimurium) definitive type (DT)104-specific sequences of mainly prophage origin
      by genomic subtractive hybridization. In the present study, the distribution of
      the prophages identified, ST104 and ST64B, and the novel prophage remnant
      designated prophage ST104B, was tested among 23 non-DT104 S. Typhimurium isolates
      of different phage types and 19 isolates of the DT104 subtypes DT104A, DT104B low
      and DT104L, and the DT104-related type U302. The four S. Typhimurium prophages
      Gifsy-1, Gifsy-2, Fels-1 and Fels-2 were also included. Analysis of prophage
      distribution in different S. Typhimurium isolates may supply additional
      information to enable development of a molecular method as an alternative to
      phage typing. Furthermore, the presence of the common DT104 antibiotic resistance
      genes for the penta-resistance type ACSSuT, aadA2, floR, pse-1, sul1 and tet(G),
      was also studied because of the authors' focus on this emerging type. Based on
      differences in prophage presence within their genome, it was possible to divide
      S. Typhimurium isolates into 12 groups. Although no clear relationship was found
      between different phage type and prophage presence, discrimination could be made
      between the different DT104 subtypes based on diversity in the presence of
      prophages ST104, ST104B and ST64B. The novel prophage remnant ST104B, which
      harbours a homologue of the Escherichia coli O157 : H7 HldD LPS assembly-related
      protein, was identified only in the 14 DT104L isolates and in the DT104-related
      U302 isolate. In conclusion, the presence of the genes for penta-resistance type
      ACSSuT, the HldD homologue containing ST104 prophage remnant and phage type
      DT104L are most likely common features of the emerging subtype of S. Typhimurium
      DT104.

PMID- 16804188
TI  - Proteus mirabilis isolates of different origins do not show correlation with
      virulence attributes and can colonize the urinary tract of mice.
AB  - Proteus mirabilis has been described as an aetiological agent in a wide range of
      infections, playing an important role in urinary tract infections (UTIs). In this
      study, a collection of P. mirabilis isolates obtained from clinical and non
      clinical sources was analysed in order to determine a possible correlation
      between origin, virulence factors and in vivo infectivity. Isolates were
      characterized in vitro, assessing several virulence properties that had been
      previously associated with P. mirabilis uropathogenicity. Swarming motility,
      urease production, growth in urine, outer-membrane protein patterns, ability to
      grow in the presence of different iron sources, haemolysin and haemagglutinin
      production, and the presence and expression of diverse fimbrial genes, were
      analysed. In order to evaluate the infectivity of the different isolates, the
      experimental ascending UTI model in mice was used. Additionally, the Dienes test
      and the enterobacterial repetitive intergenic consensus (ERIC)-PCR assay were
      performed to assess the genetic diversity of the isolates. The results of the
      present study did not show any correlation between distribution of the diverse
      potential urovirulence factors and isolate source. No significant correlation was
      observed between infectivity and the origin of the isolates, since they all
      similarly colonized the urinary tract of the challenged mice. Finally, all
      isolates showed unique ERIC-PCR patterns, indicating that the isolates were
      genetically diverse. The results obtained in this study suggest that the source
      of P. mirabilis strains cannot be correlated with pathogenic attributes, and that
      the distribution of virulence factors between isolates of different origins may
      correspond to the opportunistic nature of the organism.

PMID- 16804189
TI  - Occurrence, phylogeny and evolution of ribulose-1,5-bisphosphate
      carboxylase/oxygenase genes in obligately chemolithoautotrophic sulfur-oxidizing
      bacteria of the genera Thiomicrospira and Thioalkalimicrobium.
AB  - The occurrence of the different genes encoding ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RubisCO), the key enzyme of the Calvin-Benson-Bassham
      cycle of autotrophic CO(2) fixation, was investigated in the members of the genus
      Thiomicrospira and the relative genus Thioalkalimicrobium, all obligately
      chemolithoautotrophic sulfur-oxidizing Gammaproteobacteria. The cbbL gene
      encoding the 'green-like' form I RubisCO large subunit was found in all analysed
      species, while the cbbM gene encoding form II RubisCO was present only in
      Thiomicrospira species. Furthermore, species belonging to the Thiomicrospira
      crunogena 16S rRNA-based phylogenetic cluster also possessed two genes of green
      like form I RubisCO, cbbL-1 and cbbL-2. Both 16S-rRNA- and cbbL-based phylogenies
      of the Thiomicrospira-Thioalkalimicrobium-Hydrogenovibrio group were congruent,
      thus supporting its monophyletic origin. On the other hand, it also supports the
      necessity for taxonomy reorganization of this group into a new family with four
      genera.

PMID- 16804190
TI  - Horizontal transfer of the immunoglobulin A1 protease gene (iga) from
      Streptococcus to Gemella haemolysans.
AB  - Bacterial IgA1 proteases share the ability to cleave human IgA1 at the hinge
      region. Nature has developed this trait along at least five independent
      evolutionary lineages. To obtain further insight into the phylogeny and function
      of IgA1 proteases, the nucleotide sequence of the iga gene that encodes the IgA1
      protease was determined from two Streptococcus mitis strains and one Gemella
      haemolysans strain. Heterologous expression in Escherichia coli confirmed that
      the genes encode human IgA1-cleaving activity. IgA1 proteases from Streptococcus
      and G. haemolysans shared structural features, including a motif typical for zinc
      dependent metalloproteases of clan MA(E) family M26 and an N-terminal signal
      sequence followed by an LPXTG cell-wall-anchor motif and two putative membrane
      spanning domains. In addition, they all harboured a repeat region preceding the
      active site of the protease. In the streptococcal IgA1 proteases, a G5 domain,
      which has been suggested to bind N-acetylglucosamine, was identified.
      Conservation of these structures in otherwise diverse proteases suggests that
      they are essential to the biological function of the enzyme. The phylogenetic
      distribution of homologous iga genes and conservation of gene order in the iga
      gene region in different Streptococcus species, combined with the sequence
      homologies, strongly suggest that the iga gene is more ancient in Streptococcus
      than in G. haemolysans, and therefore that the IgA1 protease gene was transferred
      from Streptococcus to G. haemolysans.

PMID- 16804191
TI  - Ultrastructure and gliding motility of Mycoplasma amphoriforme, a possible human
      respiratory pathogen.
AB  - Despite their small size and reduced genomes, many mycoplasma cells have complex
      structures involved in virulence. Mycoplasma pneumoniae has served as a model for
      the study of virulence factors of a variety of mycoplasma species that cause
      disease in humans and animals. These cells feature an attachment organelle, which
      mediates cytadherence and gliding motility and is required for virulence. An
      essential component of the architecture of the attachment organelle is an
      internal detergent-insoluble structure, the electron-dense core. Little
      information is known regarding its underlying mechanisms. Mycoplasma
      amphoriforme, a close relative of both M. pneumoniae and the avian pathogen
      Mycoplasma gallisepticum, is a recently discovered organism associated with
      chronic bronchitis in immunosuppressed individuals. This work describes both the
      ultrastructure of M. amphoriforme strain A39(T) as visualized by scanning
      electron microscopy and the gliding motility characteristics of this organism on
      glass. Though externally resembling M. gallisepticum, M. amphoriforme cells were
      found to have a Triton X-100-insoluble structure similar to the M. pneumoniae
      electron-dense core but with different dimensions. M. amphoriforme also exhibited
      gliding motility using time-lapse microcinematography; its movement was slower
      than that of either M. pneumoniae or M. gallisepticum.

PMID- 16804192
TI  - OxLDL immune complexes activate complement and induce cytokine production by
      MonoMac 6 cells and human macrophages.
AB  - Oxidized low density lipoprotein (OxLDL) is immunogenic and induces autoimmune
      responses in humans. OxLDL antibodies are predominantly of the proinflammatory
      IgG1 and IgG3 isotypes. We tested the capacity of immune complexes prepared with
      copper-oxidized human LDL and affinity chromatography-purified human OxLDL
      antibodies [OxLDL-immune complexes (ICs)] to activate complement and to induce
      cytokine release by MonoMac 6 (MM6) cells and by primary human macrophages. The
      levels of C4d and C3a were significantly higher in human serum incubated with
      OxLDL-ICs than after incubation with OxLDL or OxLDL antibody, indicating
      complement activation by the classical pathway. MM6 cells and primary human
      macrophages were incubated with OxLDL-ICs, with or without prior conditioning
      with interferon-gamma. After 18 h of incubation, both MM6 cells and primary human
      macrophages released significantly higher levels of proinflammatory cytokines
      after incubation with OxLDL-ICs than after incubation with OxLDL or with OxLDL
      antibody, both in primed and unprimed cells. OxLDL-ICs were more potent
      activators of MM6 cells than keyhole limpet hemocyanin-ICs. Blocking Fc gamma
      receptor I (FcgammaRI) with monomeric IgG1 significantly depressed the response
      of MM6 cells to OxLDL-ICs. In conclusion, human OxLDL-ICs have proinflammatory
      properties, as reflected by their capacity to activate the classical pathway of
      complement and to induce proinflammatory cytokine release from MM6 cells and
      primary human macrophages.

PMID- 16804193
TI  - Type 2 diabetes-an introduction to the development and use of animal models.
AB  - Although the epidemiology of type 2 diabetes (T2D) has been well described, there
      is much about the disease that remains unclear. For example, lifestyle factors
      including increased body weight with visceral fat deposition and insufficient
      physical activity-are thought to be primary contributors to the adverse changes
      in the metabolism of muscle and fat cells that comprise the first stage of the
      disease. However, the precise mechanisms underlying these initial alterations are
      incompletely understood. Other, less obvious questions relate to the presence of
      sex differences in the development and health consequences of T2D, the
      etiological role of the central nervous system ("stress"), and the potential
      evolutionary origins of T2D susceptibility. Some of these issues can be resolved
      by further study of human populations. However, many questions can be answered
      only through the kinds of controlled prospective studies that are conducted with
      appropriate animal models. The use of such models can be an invaluable part of an
      overall strategy designed to elucidate the mechanisms underlying the development
      of T2D, understand the natural history of the disease, identify targets for
      therapy, and evaluate interventions. Current evidence indicates that no single
      animal model replicates the development of human T2D in all of its details.
      Nonetheless, the existing models (e.g., naturally occurring and genetically
      modified rodents, cats, pigs, and nonhuman primates) offer researchers a rich
      array of opportunities to investigate the myriad complexities of T2D. The
      individual contributions comprising this issue of ILAR Journal review the
      research that has been conducted on many of these animals.

PMID- 16804194
TI  - Animal models of type 2 diabetes: clinical presentation and pathophysiological
      relevance to the human condition.
AB  - The prevalence of diabetes throughout the world has increased dramatically over
      the recent past, and the trend will continue for the foreseeable future. One of
      the major concerns associated with diabetes relates to the development of micro-
      and macrovascular complications, which contribute greatly to the morbidity and
      mortality associated with the disease. Progression of the disease from
      prediabetic state to overt diabetes and the development of complications occur
      over many years. Assessment of interventions designed to delay or prevent disease
      progression or complications in humans also takes years and requires tremendous
      resources. To better study both the pathogenesis and potential therapeutic
      agents, appropriate animal models of type 2 diabetes (T2D) mellitus are needed.
      However, for an animal model to have relevance to the study of diabetes, either
      the characteristics of the animal model should mirror the pathophysiology and
      natural history of diabetes or the model should develop complications of diabetes
      with an etiology similar to that of the human condition. There appears to be no
      single animal model that encompasses all of these characteristics, but there are
      many that provide very similar characteristics in one or more aspects of T2D in
      humans. Use of the appropriate animal model based on these similarities can
      provide much needed data on pathophysiological mechanisms operative in human T2D.

PMID- 16804195
TI  - Molecular approaches to study control of glucose homeostasis.
AB  - Type 2 diabetes is a polygenic disease that can lead to severe complications in
      multiple tissues. Rodent models have been used widely for investigating the
      pathophysiology underlying type 2 diabetes and for examining the potential link
      with obesity, largely due to the limitations of invasive testing and of studying
      detailed molecular mechanisms in human tissues. Among rodents, the mouse model is
      especially popular because mice are easy to manipulate genetically, have a short
      generation time, and are relatively inexpensive. The most commonly used inbred
      mouse strains are reviewed in addition to several genetically engineered mouse
      models that have been generated to study type 2 diabetes in the context of
      obesity, with a focus on insulin, leptin, and peroxisome proliferator-activated
      receptor (PPAR) signaling pathways.

PMID- 16804196
TI  - Nutritionally induced diabetes in desert rodents as models of type 2 diabetes:
      Acomys cahirinus (spiny mice) and Psammomys obesus (desert gerbil).
AB  - The dietary effects of hyperglycemia increasingly result in type 2 diabetes in
      humans. Two species, the spiny mice (Acomys cahirinus) and the desert gerbil
      (Psammomys obesus), which have different metabolic responses to such effects, are
      discussed. Spiny mice exemplify a pathway that leads to diabetes without marked
      insulin resistance due to low supply of insulin on abundant nutrition, possibly
      characteristic of a desert animal. They respond with obesity and glucose
      intolerance, beta-cell hyperplasia, and hypertrophy on a standard rodent diet
      supplemented with fat-rich seeds. The accompanying hyperglycemia and
      hyperinsulinemia are mild and intermittent but after a few months, the enlarged
      pancreatic islets suddenly collapse, resulting in loss of insulin and ketosis.
      Glucose and other secretagogues produce only limited insulin release in vivo and
      in vitro, pointing to the inherent disability of the beta-cells to respond with
      proper insulin secretion despite their ample insulin content. On a 50% sucrose
      diet there is marked lipogenesis with hyperlipidemia without obesity or diabetes,
      although beta-cell hypertrophy is evident. P.obesus is characterized by muscle
      insulin resistance and the inability of insulin to activate the insulin signaling
      on a high-energy (HE) diet. Insulin resistance imposes a vicious cycle of
      Hyperglycemia and compensatory hyperinsulinemia, leading to beta-cell failure and
      increased secretion of proinsulin. Ultrastructural studies reveal gradual
      disappearance of beta-cell glucokinase, GLUT 2 transporter, and insulin, followed
      by apoptosis of beta-cells. Studies using the non-insulin-resistant HE diet-fed
      animals maintained as a control group are discussed. The insulin resistance that
      is evident to date in the normoglycemic state on a low-energy diet indicates
      sparing of glucose fuel in muscles of a desert-adapted animal for the benefit of
      glucose obligatory tissues. Also discussed are the effect of Psammomys age on the
      disabetogenicity of the HE diet; the impaired function of several components of
      the insulin signal transduction pathway in muscles, which reduces the
      availability of GLUT4 transporter; the testing of several antidiabetic modalities
      for the prevention of nutritional diabetes in Psammomys; and various
      complications related to the diabetic condition.

PMID- 16804197
TI  - Islet amyloid polypeptide (IAPP) transgenic rodents as models for type 2
      diabetes.
AB  - Blood glucose concentrations are maintained by insulin secreted from beta-cells
      located in the islets of Langerhans. There are approximately 2000 beta-cells per
      islet, and approximately one million islets of Langerhans scattered throughout
      the pancreas. The islet in type 2 diabetes mellitus (T2D) has deficient beta-cell
      mass due to increased beta-cell apoptosis and islet amyloid derived from islet
      amyloid polypeptide (IAPP). Accumulating evidence implicates toxic IAPP oligomers
      in the mediation of beta-cell apoptosis in T2D. Humans, monkeys, and cats express
      an amyloidogenic toxic form of IAPP and spontaneously develop diabetes
      characterized by islet amyloid deposits. However, longitudinal studies of islet
      pathology in humans are impossible, and studies in nonhuman primates and cats are
      costly and impractical. Rodent IAPP is not amyloidogenic, thus commonly used
      rodent models of diabetes do not recapitulate islet pathology in humans. To
      investigate the diabetogenic role of human IAPP (h-IAPP), several mouse models
      and, more recently, a rat model transgenic for h-IAPP have been developed.
      Studies in these models have revealed that the toxic effect of h-IAPP on beta
      cell apoptosis demonstrates a threshold-dependent effect. Specifically,
      increasing h-IAPP transgene expression by breeding or induction of insulin
      resistance leads to increased beta-cell apoptosis and diabetes. These transgenic
      rodent models for h-IAPP provide an opportunity to elucidate the mechanisms
      responsible for h-IAPP-induced beta-cell apoptosis further and to test novel
      approaches to the prevention and treatment of T2D.

PMID- 16804198
TI  - Feline models of type 2 diabetes mellitus.
AB  - Feline diabetes mellitus (FDM) closely resembles human type 2 diabetes mellitus
      (T2DM) in many respects including clinical, physiological, and pathological
      features of the disease. These features include age of onset of FDM in middle
      age, association with obesity, residual but declining insulin secretion,
      development of islet amyloid deposits, loss of approximately 50% of beta-cell
      mass, and development of complications in several organ systems including
      peripheral polyneuropathy and retinopathy. Many of the pathological aspects of
      the disease are also experimentally inducible, facilitating study of the
      pathogenesis of these lesions. Physiological aspects of FDM and obesity are also
      well studied in the cat and provide an excellent basis for comparative studies of
      human T2DM. The relatively short generation time of cats along with breed
      predispositions to development of FDM may allow for more rapid screening and
      identification of genetic markers for diabetes susceptibility. FDM, in both
      spontaneous and inducible forms, therefore provides a good animal model of human
      T2DM and may provide additional insights into the pathogenesis of this important
      condition.

PMID- 16804199
TI  - Swine models of type 2 diabetes mellitus: insulin resistance, glucose tolerance,
      and cardiovascular complications.

PMID- 16804200
TI  - Old world nonhuman primate models of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is a major health problem of increasing incidence. To
      better study the pathogenesis and potential therapeutic agents for this disease,
      appropriate animal models are needed. Old World nonhuman primates (NHPs) are a
      useful animal model of type 2 diabetes; like humans, the disease is most common
      in older, obese animals. Before developing overt diabetes, NHPs have a period of
      obesity-associated insulin resistance that is initially met with compensatory
      insulin secretion. When either a relative or absolute deficiency in pancreatic
      insulin production occurs, fasting glucose concentrations begin to increase and
      diabetic signs become apparent. Pathological changes in pancreatic islets are
      also similar to those seen in human diabetics. Initially there is hyperplasia of
      the islets with abundant insulin production typically followed by replacement of
      islets with islet-associated amyloid. Diabetic NHPs have detrimental changes in
      plasma lipid and lipoprotein concentrations, lipoprotein composition, and
      glycation, which may contribute to progression of atherosclerosis. As both the
      prediabetic condition (similar to metabolic syndrome in humans) and overt
      diabetes become better defined in monkeys, their use in pharmacological studies
      is increasing. Likely due to their genetic similarity to humans and the similar
      characteristics of the disease in NHPs, NHPs have been used to study recently
      developed agonists of the peroxisome proliferators-activated receptors.
      Importantly, agonists of the different receptor subclasses elicit similar
      responses in both humans and NHPs. Thus, Old World NHPs are a valuable animal
      model of type 2 diabetes to study disease progression, associated risk factors,
      and potential new treatments.

PMID- 16804201
TI  - E-alert 27 January: Chikungunya outbreak in Reunion, a French overseas
      department.

PMID- 16804202
TI  - No new human infections with A/H5N1 in Turkey but national measures and
      international support continue.

PMID- 16804203
TI  - Chikungunya outbreak in Reunion: epidemiology and surveillance, 2005 to early
      January 2006.

PMID- 16804205
TI  - Introduction of pneumococcal conjugate vaccine into the Norwegian childhood
      vaccination programme.

PMID- 16804204
TI  - What is epidemic intelligence, and how is it being improved in Europe?

PMID- 16804206
TI  - Avian influenza H5N1 detected in poultry in Nigeria, further human cases reported
      in Iraq, Indonesia and China.

PMID- 16804207
TI  - New case of transfusion-associated vCJD in the United Kingdom.

PMID- 16804208
TI  - Unusual phage pattern of Salmonella Typhimurium isolated from Swedish patients
      and Italian salami.

PMID- 16804209
TI  - Surveillance system in place for the 2006 Winter Olympic Games, Torino, Italy,
      2006.

PMID- 16804210
TI  - Avian influenza detected in swans in central Europe, and continues spread in
      Nigeria.

PMID- 16804211
TI  - Clinical influenza activity in Europe is still low, with influenza B virus being
      dominant: an update from EISS.

PMID- 16804213
TI  - HIV and STIs increasing in the Netherlands according to latest surveillance data.
AB  - In 2004, numbers of sexually transmitted infections (STIs) increased in the
      Netherlands compared with 2003.

PMID- 16804212
TI  - Anthrax in animals and a farmer in Alto Adige, Italy.

PMID- 16804216
TI  - More detections of avian influenza in wild birds in Europe: Commission approves
      limited poultry vaccination.

PMID- 16804217
TI  - Current measles outbreak in Greece.

PMID- 16804218
TI  - Rubella outbreak in young adults of Brazilian origin in a Barcelona suburb,
      October-December 2005.

PMID- 16804219
TI  - VTEC infections and livestock-related exposures in Scotland, 2004.

PMID- 16804220
TI  - An outbreak of haemolytic uraemic syndrome associated with minced beef, Norway,
      January-February 2006: preliminary report.

PMID- 16804221
TI  - Further spread of avian influenza in Europe, detection in French farmed birds and
      German cat.

PMID- 16804222
TI  - Chikungunya outbreak on Reunion: update.

PMID- 16804223
TI  - Introduction of pneumococcal conjugate vaccine to the UK childhood immunisation
      programme, and changes to the meningitis C and Hib schedules.

PMID- 16804224
TI  - Scarlet fever outbreak in two nurseries in southwest England.

PMID- 16804226
TI  - Measles outbreak in the Ukraine, 2005-2006.

PMID- 16804227
TI  - Poliomyelitis outbreaks in Africa and Asia: importation of infections a serious
      risk for polio-free countries with low vaccine coverage.

PMID- 16804228
TI  - Tenth EU country detects highly pathogenic avian influenza in wild birds.

PMID- 16804229
TI  - Recent increase in S. Paratyphi A phage type 1 and S. Typhi Vi-phage type E1 in
      England and Wales, associated with travel to the Indian subcontinent.

PMID- 16804231
TI  - Seven human cases of H5N1 infection confirmed in Azerbaijan, and one case in
      Egypt.

PMID- 16804233
TI  - Outbreaks of measles in Germany, 2006.

PMID- 16804232
TI  - World TB day: European countries report over 400,000 tuberculosis cases in 2004.

PMID- 16804234
TI  - First cases of rubella infection during pregnancy detected by new reporting
      system in Italy.

PMID- 16804235
TI  - Worldwide distribution of HPV types in women with normal cervical cytology and in
      women with cervical adenocarcinoma.

PMID- 16804237
TI  - Early Containment Strategy: a protocol to contain pandemic influenza when it
      first emerges globally.

PMID- 16804238
TI  - Recommended composition of the 2006/07 influenza vaccine.

PMID- 16804239
TI  - Measles outbreak in the region of Madrid, Spain, 2006.

PMID- 16804240
TI  - Measles outbreak in the Oresund region of Denmark and Sweden.

PMID- 16804241
TI  - Biomechanics of skeletal anchorage. Part 2: Class II nonextraction treatment.

PMID- 16804242
TI  - The advantages of paperless operation.

PMID- 16804243
TI  - Tips for using fixed functional appliances.

PMID- 16804244
TI  - Two-way communication.

PMID- 16804245
TI  - Comparison of bond strengths using different curing lights.

PMID- 16804246
TI  - Midline correction with mini-screw anchorage and lingual appliances.

PMID- 16804247
TI  - Surgical-orthodontic correction of long-face syndrome.

PMID- 16804248
TI  - Eruption of an impacted maxillary central incisor with an unusual dilaceration.

PMID- 16804249
TI  - A light-focusing tool for bonding fiber-reinforced composite retainers.

PMID- 16804251
TI  - The only constant.

PMID- 16804250
TI  - The effects of orthodontic appliances on wind-instrument players.

PMID- 16804252
TI  - Bonding in today's orthodontic practice.

PMID- 16804253
TI  - The Forsus Fatigue Resistant Device.

PMID- 16804254
TI  - Intrusion of overerupted maxillary molars with miniscrew anchorage.

PMID- 16804255
TI  - Seizures associated with solitary cysticercus granuloma: antiepileptic drugs for
      how long?

PMID- 16804256
TI  - The heuristics of craniospinal epidermoid tumors.

PMID- 16804257
TI  - Neuropathological spectrum of lesions associated with intractable epilepsies: a
      10-year experience with a series of 153 resections.
AB  - BACKGROUND: Surgical management of intractable epilepsies is currently an
      established mode of therapy in various clinical settings. AIMS: To
      retrospectively evaluate the neuropathological findings in both temporal and
      extratemporal lobe resections in such patients. MATERIALS AND METHODS: The study
      included resected specimens from patients with intractable epilepsy managed at a
      tertiary care hospital of India, during a 10-year period (1995-2004). RESULTS: A
      total of 153 patients, with mean age of 19.4 years and male predominance (73.2%)
      were included in the study. Overall, there was a predilection for the temporal
      lobe (73.2%), while 41cases were extratemporal in location. On histopathology,
      mesial temporal sclerosis (MTS) (24.8%) was the commonest lesion, followed by
      tumors (19.6%) and isolated focal cortical dysplasia (FCD - 15.11%). Other less
      common findings included Rasmussen encephalitis, non-specific gliosis and
      vascular malformations. In addition, 20.9% (32 cases) had dual lesions, majority
      of which included FCD with ganglioglioma (15 cases) or with dysembryoplastic
      neuroepithelial tumor (12 cases). In the temporal lobe, neoplasms and dual
      lesions formed the majority (apart from MTS), unlike dual lesions followed by
      neoplasms and FCD, in the extratemporal location. CONCLUSION: This series
      demonstrates that most patients with chronic intractable epilepsy have
      significant histopathological findings and highlights the neuropathological
      spectrum of such lesions, in the Indian context. This was similar to that
      reported from the West, but different from the single Indian series available in
      the literature. Further, the overall profile of temporal lobe lesions was not
      different from the extratemporal ones.

PMID- 16804258
TI  - Knowledge of stroke among stroke patients and their relatives in Northwest India.
AB  - BACKGROUND: The knowledge of warning symptoms and risk factors for stroke has not
      been studied among patients with stroke in developing countries. AIMS: We aimed
      to assess the knowledge of stroke among patients with stroke and their relatives.
      SETTINGS AND DESIGN: Prospective tertiary referral hospital-based study in
      Northwest India. MATERIALS AND METHODS: Trained nurses and medical interns
      interviewed patients with stroke and transient ischemic attack and their
      relatives about their knowledge of stroke symptoms and risk factors. STATISTICAL
      ANALYSIS: Univariable and multivariable logistic regression were used. RESULTS:
      Of the 147 subjects interviewed, 102 (69%) were patients and 45 (31%) were
      relatives. There were 99 (67%) men and 48 (33%) women and the mean age was 59.7+/
      14.1 years. Sixty-two percent of respondents recognized paralysis of one side as
      a warning symptom and 54% recognized hypertension as a risk factor for stroke. In
      the multivariable logistic regression analysis, higher education was associated
      with the knowledge of correct organ involvement in stroke (OR 2.6, CI 1.1- 6.1, P
      =0.02), whereas younger age (OR 2.7, CI 1.1-7.0, P =0.04) and higher education
      (OR 4.1, CI 1.5-10.9, P =0.005) correlated with a better knowledge regarding
      warning symptoms of stroke. CONCLUSIONS: In this study cohort, in general, there
      is lack of awareness of major warning symptoms, risk factors, organ involvement
      and self-recognition of stroke. However younger age and education status were
      associated with better knowledge. There is an urgent need for awareness programs
      about stroke in this study cohort.

PMID- 16804259
TI  - Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug
      treatment of solitary cysticercus granulomas.
AB  - BACKGROUND: It is now agreed that the prognosis of seizure disorder due to
      solitary cysticercus granuloma (SCG) is generally good. However, the choice
      antiepileptic drugs (AEDs) remain empirical, with no comparative trials of
      different AEDs being available. AIMS: To determine the safety and efficacy
      (measured by the incidence of 'treatment failure') of clobazam in comparison to
      standard treatment with phenytoin-sodium for prevention of seizures in persons
      with solitary cysticercus granulomas (SCGs). SETTINGS AND DESIGN: This pilot
      study was conducted in a neurology department of a medical college hospital in
      the form of a prospective, randomized, open-labeled trial. MATERIALS AND METHODS:
      Forty-eight patients with seizures due to SCG were randomized in an open-labeled
      trial to either, clobazam (1 mg/kg oral loading followed by 0.5 mg/kg/d) (n=21)
      or phenytoin (15 mg/kg, oral loading in 3 divided doses over 24 h, followed by 5
      mg/kg/d) (n=27). They were followed over 6 months with the primary outcome
      measure being treatment failure (either discontinuation or modification of AEDs)
      due to either adverse effects or breakthrough seizures. RESULTS: Treatment
      failures were noted to be significantly less common (P =0.03) in the clobazam
      treated group (n=1; 4.7%) than in phenytoin-treated group (n=9; 33.3%). These
      included one patient (4.7%) in the clobazam-group who had breakthrough seizures
      and 3 (11.1%) who had breakthrough seizures and 6 (22.2%) in the phenytoin
      treated group who had adverse effects requiring treatment discontinuation.
      CONCLUSIONS: Clobazam was well tolerated, safe and more effective than phenytoin
      in the AED treatment of patients with SCG.

PMID- 16804260
TI  - Endoscopic third ventriculostomy in infants.
AB  - BACKGROUND: Endoscopic third Ventriculostomy (ETV) is one of the surgical options
      for obstructive hydrocephalus. There are varying opinions about results of ETV in
      infants. We are therefore presenting the results of ETV in 54 infants. MATERIALS
      AND METHODS: A prospective study of 54 infants undergoing ETV in our institution
      in the last 2 years was carried out. There were 48 cases of congenital
      hydrocephalus with aqueductal stenosis, 6 of post tubercular meningitis
      hydrocephalus. Average follow up was 18 months. RESULTS: There was 83.3% (45
      cases) clinical success rate in our study. Infection, persistent cerebro-spinal
      fluid (CSF) leak and bleeding occurred in 4 (8%) cases each while blockage of
      stoma was observed in 8 (14.8%) patients. Majority of ETV stoma closure (6 out of
      total 8) occurred following infection (4) or bleeding during surgery (2). One
      patient (2%) had transient diabetes insipidus. Overall failure rate in our study
      was 16.7% (8 stoma blocks and 1 procedure abandoned). Low birth weight pre mature
      infants had higher failure rate (3 out of 5 infants 60%) compared to full term
      infants with normal birth weight (12.3%). Age did not have any impact on the
      success rate (P>0.05). Success rates were not significanlty different in patients
      with aqueductal stenosis (85.4%) and TBM (66.6%) (Fisher's exact test, P=0.3).
      CONCLUSION: ETV was fairly safe and effective in full term normal birth weight
      infants while the results in low birth weight pre mature infants were poor.

PMID- 16804261
TI  - Percutaneous laser disc decompression: clinical experience at SCTIMST and long
      term follow up.
AB  - BACKGROUND: Low backache (LBA) is now increasing in younger population due to
      misdirected spinal kinetics secondary to improper posture, heavy load lifting and
      motorbike driving. Hence minimally invasive procedures are increasingly sought
      after. Among these, PLDD is currently popular and in use. We present our long
      term follow-up in the use of Nd:YAG laser for PLDD. AIM: To evaluate the efficacy
      of PLDD in treatment of contained herniation of lumbar discs & long term follow
      up results. MATERIALS AND METHODS: Forty patients with contained lumbar disc
      herniation on MRI and who did not respond to 6 weeks conservative treatment were
      subjected to PLDD. L4-5 disc was treated in 31, L5-S1 in 12 and L1-2 and L3-4 in
      one each. Nd:YAG laser at 1064 nm was used for the procedure. Total laser energy
      of 1500-2000 Joules was delivered at the disc space depending upon the size.
      RESULTS: There was immediate pain relief in 32/40 (80%). According to MacNab
      criteria good to fair response was seen in 37/40 (92%) and 3 patients (7.5%)
      responded poorly to this treatment. On follow up which ranged from 1 to 7 years,
      34/40 (85%) had pain relief with no need for further treatment. COMPLICATIONS:
      Significant pain at local puncture site was experienced by 8 (20%), pain during
      lasing was experienced by one. One patient developed muscular spasm. CONCLUSION:
      Percutaneous laser disc decompression is a safe, relatively noninvasive and
      effective treatment modality for contained, nonsequestered, herniated lumbar disc
      disease in carefully selected patients.

PMID- 16804262
TI  - Retinal nerve fiber layer analysis in idiopathic intracranial hypertension.
AB  - BACKGROUND: The chronic nature of idiopathic intracranial hypertension (IIH)
      represents a risk factor for progressive optic nerve damage and structural
      abnormalities of the retina. AIM: We measured the retinal nerve fiber layer
      (RNFL) thickness in patients followed with the diagnosis of IIH who had no or
      mild visual impairment to search for possible structural alterations in the
      retina for diagnostic and prognostic purposes. SETTINGS AND DESIGN: Case-control
      prospective study. MATERIALS AND METHODS: The study group consisted of 12 women
      followed and treated with the diagnosis of IIH in our clinic. The selection
      criteria were the, normal optic nerve, normal visual fields or mild visual field
      defects (Grade 1-3) by Humphrey perimeter. Randomly assigned, age-matched 12
      healthy women were taken as the control group. Retinal nerve fiber layer
      thickness was evaluated with scanning laser polarimetry and both eyes were
      studied for each case in both groups. STATISTICAL ANALYSIS USED: Mann-Whitney U
      test. RESULTS: The mean ages of the patient and the control groups were 34.58+/
      4.2 and 34.42+/-5.7 years respectively (P=0.87). The mean duration of disease was
      5.5+/-3 years. Some parameters related to RNFL thickness were found to differ
      significantly between patients with IIH and control subjects. Namely superior
      ratio (P=0.007), inferior ratio (P=0.039), superior-nasal ratio (P=0.025),
      maximum modulation (P=0.01) and symmetry (P=0.006) were lower in the patient
      group than controls. CONCLUSION: Scanning laser polarimetry might be a good
      adjunct for determining possible structural affects of IIH on the retina in
      patients with no or mild visual impairment.

PMID- 16804263
TI  - Effectiveness of oxcarbazepine in symptomatic treatment of painful diabetic
      neuropathy.
AB  - BACKGROUND: Both basic and clinical research has demonstrated that antiepileptic
      drugs can be effective in alleviating neuropathic pain. It was hypothesized that
      oxcarbazepine might be effective in reducing the symptoms of painful diabetic
      neuropathy. AIMS: To investigate the long-term efficacy and safety of
      oxcarbazepine in symptoms of painful diabetic neuropathy. MATERIALS AND METHODS:
      This study included thirty-eight painful diabetic neuropathy patients, which were
      screened with clinical assessment and electrophysiological studies. The efficacy
      and safety of oxcarbazepine were evaluated according to the changes in pain
      intensity and social interference subitems scores of Short-form Brief Pain
      Inventory besides electrophysiological studies at the end of six months of the
      treatment. STATISTICAL ANALYSIS: The Students t, Mann-Whitney U and Rank Sum test
      and Chi-square tests were applied to examine variables differences. The level of
      statistical significance was chosen to be P<0.05. RESULTS: A significant
      difference was found in all of subitems of pain intensity and social interference
      at the end of the study according to the baseline scores. Improvement was
      observed in 52.7%, 63.1%, 55.3% and 63.2% of patients for worst, least, average
      and pain right now at the end of six months, respectively. Improvement was
      observed as 60.6%, 63.2%, 52.6%, 60.5%, 68.4% and 63.2% for general activity,
      mood, walk, work, people relations, sleep and life enjoyment subitems,
      respectively. None of these patients had any prominent side effect leading to
      discontinue the treatment. CONCLUSION: Long-term oxcarbazepine treatment was
      found to be effective and safe in the symptoms of painful diabetic neuropathy.

PMID- 16804264
TI  - The effects of high dose progesterone on neural tube development in early chick
      embryos.
AB  - BACKGROUND: Although folic acid deficiency is known to be one of the factors in
      the development of spina bifida and other neural tube defects (NTD) the exact
      pathophysiology still remains unclear. Progesterone is an endogenous hormone
      which increases significantly during pregnancy. AIMS: We aimed to study the
      possible negative effects of high dose progesterone on neural tube development in
      early chick embryos. In order to test our hypothesis, early chick embryos were
      exposed to physiological saline, normal and high doses of progesterone. SETTINGS
      AND DESIGN: 160 fertile, specific pathogen free white leghorn eggs (Gallus
      gallus), all at stage eight of development were divided into four equal groups.
      MATERIALS AND METHODS: The first group was incubated without any operation. The
      second group was injected with physiological saline. The third and fourth groups
      were injected with two and twenty times more than physiologic doses of
      progesterone respectively. After 48 hours of incubation, all embryos were
      analyzed for the presence of NTDs under light microscopy. STATISTICAL ANALYSIS
      USED: None. RESULTS: At 48 hours of incubation, 84% (135/160) of the embryos
      passed characteristics of Stage 12 development and were included to the study.
      None of the eggs in the first three groups showed NTDs, whereas 81.8% (27/33) of
      the eggs in the fourth group showed NTDs. CONCLUSIONS: Our study showed that
      progesterone at levels twenty times more than its physiologic level might cause
      NTDs. Further studies are needed to explain the mechanisms of this teratogenic
      effect.

PMID- 16804265
TI  - Investigation on mtDNA deletions and twinkle gene mutation (G1423C) in Iranian
      patients with chronic progressive external opthalmoplagia.
AB  - BACKGROUND: Chronic progressive external ophthalmoplagia (CPEO) is a phenotypic
      mitochondrial disorder that affects external ocular and skeletal muscles and is
      associated with a single or multiple mitochondrial DNA (mtDNA) deletions and also
      nuclear gene mutations. There are also some reports about the relationship
      between CPEO and the nuclear Twinkle gene which encodes a kind of mitochondrial
      protein called Twinkle. AIMS: To study the mtDNA deletions and Twinkle gene
      G1423C point mutation in Iranian patients with CPEO. MATERIALS AND METHODS: We
      collected 23 muscle samples from patients with CPEO, 9 women (mean age 34.3
      years) and 14 men (36.7 years). Multiplex polymerase chain reaction (PCR) method
      was used to find the presence of single or multiple deletions in mtDNA. Single
      stranded conformational polymorphism (SSCP) and restriction fragment length
      polymorphism (PCR-RFLP) methods were carried out to investigate point mutation
      (G1423C) in the Twinkle gene in all DNA samples. RESULTS: Different sizes of
      mtDNA deletions were detected in 16 patients (69.6%). Each of the 5.5, 7, 7.5 and
      9 kb deletions existed only in 1 patient. Common deletion (4977bp) and 8 kb
      deletion were detected in 5 and 3 patients respectively. Multiple deletions were
      also present in 4 patients. Out of 23 patients included in our study, two cases
      (8.7%) had Twinkle gene mutation (G1423C) and 5 patients (21.7%) did not show any
      deletions in mtDNA or the Twinkle gene mutation. CONCLUSION: Our study provides
      evidence that the investigation of mtDNA and Twinkle gene mutations in CPEO may
      help with early diagnosis and prevention of the disease. Patients who did not
      show deletions in the mtDNA or G1423C mutation in the Twinkle gene may have other
      mtDNA, Twinkle or nuclear gene mutations.

PMID- 16804266
TI  - Comparison of valporic acid efficacy in familial versus sporadic cases of
      juvenile myoclonic epilepsy.
AB  - BACKGROUND: Juvenile myoclonic epilepsy is a heterogeneous syndrome, both in
      genetic and clinical aspects. AIMS: This study was conducted to compare the
      efficacy of valproic acid in familial versus sporadic cases of this syndrome.
      SETTINGS AND DESIGN: Seventy patients with JME were identified; 24 patients
      (34.3%) had positive history of JME in their first degree relatives (group I) and
      46 patients (65.7%) were sporadic (group II). MATERIALS AND METHODS: Valproic
      acid was started for the patients with upward titration. The cases were followed
      for one year after final titration of the drug with regular blood monitoring.
      Patients, who had no myoclonic, absence and grand mal seizures within one year,
      were considered excellent responders. STATISTICAL ANALYSIS: We used Student T
      test and Fisher's exact test for quantitative and qualitative variables
      respectively. Logistic Regression test was used to evaluate the predictive
      factors for final treatment outcomes. RESULTS: Mean dosage of valproic acid was
      800 mg/d in both groups (13 mg/kg and 12.4 mg/kg respectively). Mean therapeutic
      levels of the drug in group I and II were 74 microg/ml and 78.4 microg/ml
      respectively. Excellent responders' rate was 66.7% in group I and 76.1% in group
      II. History of absences and older age at the onset of grand mal seizures
      decreased excellent responders' rate in both groups. CONCLUSIONS: Considering
      response to valproic acid, there is no significant difference in familial versus
      sporadic cases of JME, whereas history of absences and older age at the onset of
      grandmal seizures, decrease the probability of being excellent responders in this
      syndrome.

PMID- 16804267
TI  - Microendoscopic discectomy for prolapsed lumbar intervertebral disc.
AB  - BACKGROUND: Lumbar disc prolapse is a common problem and the current surgical
      standard for its treatment is a microsurgical discectomy. Microendoscopic
      discectomy (MED) is a minimally invasive spinal procedure being done successfully
      for prolapsed intervertebral disc disease. AIMS: We report the technique, outcome
      and complications seen in 107 cases of prolapsed lumbar intervertebral disc who
      underwent MED. SETTING AND DESIGN: The study was carried out at the Department of
      Neurosurgery, at a tertiary hospital in South India and the data was collected
      prospectively. MATERIALS AND METHODS: 107 patients with prolapsed lumbar
      intervertebral disc who were seen at our institution between November 2002 and
      January 2006 were included in the study. Data was collected prospectively. The
      METRx system (Medtronic Sofamor Danek, Memphis,TN) was used to perform MED.
      Outcome assessment was done by the modified Macnab criteria. RESULTS: 107
      patients (67 males, 40 females) underwent MED for prolapsed lumbar intervertebral
      disc. Follow up ranged from 2 to 40 months with a mean follow up 12.9 months.
      Seventy six patients had an excellent outcome, 22 patients had a good outcome, 5
      patients had a fair outcome and 3 patients had a poor outcome. One patient with a
      long dural tear required conversion to a standard microdiscectomy and was
      excluded from outcome assessment. Complications included dural puncture with K
      wire (1), dural tear (2), superficial wound infection (1), discitis (1) and
      recurrent disc prolapse (2). CONCLUSIONS: Microendoscopic Discectomy (MED) is a
      safe and effective procedure for the treatment of prolapsed lumbar intervertebral
      disc.

PMID- 16804268
TI  - Adrenoleukodystrophy manifesting as spinocerebellar degeneration.
AB  - X-linked adrenoleukodystrophy (XALD) is an inherited disorder of peroxisomal
      metabolism. Atypical presentations have been occasionally reported in literature.
      However, extrapyramidal and cerebellar manifestations are distinctly rare. We
      report a patient of X-linked adrenoleukodystrophy with cranial and cervical
      dystonia and neurological presentation resembling spinocerebellar degeneration
      followed by a brief review of relevant literature.

PMID- 16804269
TI  - Emery dreifuss muscular dystrophy: a clinico-pathological study.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is a rare and genetically heterogeneous
      disorder. We report two patients with emerin deficient X-linked EDMD and two
      probable patients with EDMD with typical early contractures, progressive muscle
      weakness and cardiac involvement. Family history was noted in one case. Muscle
      biopsy revealed features of dystrophy in all.

PMID- 16804270
TI  - Clozapine-responsive cluster headache.
AB  - Headaches are commonly associated with various psychiatric disorders. The
      comorbidity of migraine and psychiatric disorders has been well documented. Here
      we present a case of schizophrenia with comorbid headache treated with clozapine.
      The patient's headache fulfilled the diagnostic criteria for cluster headache
      (CH). To our knowledge this is the first report of CH responding to clozapine
      therapy. The relationship of headache and psychiatric disorders is a matter of
      debate and there has been very little research on the aspect of causality or
      direction of causation. The response of both the conditions to a serotonin
      dopamine antagonist such as clozapine might be important in giving newer insights
      into the pathogenesis of these disorders. It also has the clinical implication of
      being useful in patients with dual diagnosis.

PMID- 16804272
TI  - Hypomania as an aura in migraine.
AB  - We report a 19-year-old man presenting to the department of Psychiatry for the
      evaluation of prominent behavioral symptoms associated with episodic headaches,
      with normal inter-episodic periods. A diagnosis of classic migraine with
      hypomanic aura was made. Other possible co-morbid or causative illnesses were
      excluded and preventive therapy with valproate was started due to the prominent
      affective symptoms as a part of the migranous aura. With this the frequency of
      headaches gradually decreased over the next four months. He was followed up for 2
      years when he was found to be symptom-free. Recent research into the mechanisms
      of migraine has identified that the cortical hyperexcitability and an imbalance
      between neuronal inhibition and excitement mediated by gamma-aminobutyric acid
      and excitatory amino acids respectively may be the underlying mechanism. The high
      rate of affective disorders in patients with migraine, association of migraine
      with an aura comprising of mood symptoms and good response to treatment with mood
      stabilisers might give newer insights into the pathophysiology of mood disorder
      as well.

PMID- 16804271
TI  - Histological characteristics of arterialized medullary vein in spinal dural
      arteriovenous fistulas related with clinical findings: report of five cases.
AB  - The histological features of arterialized medullary vein (MV) in spinal dural
      arteriovenous fistulas (SDAVF) were studied in five consecutive patients who
      presented with progressive congestive myelopathy. Retrograde venous filling on
      preoperative angiography was recognized as being severe in 3 cases and moderate
      in 2 cases. Direct intradural interruption of the arterialized MV was performed
      in all patients. The arterialized MV was sampled and examined histologically to
      determine the percentage of the hyperplasia of venous wall (hypertrophic ratio).
      Histological examination of arterialized MV showed that hypertrophic alteration
      of venous wall structure was due to hyperplasia of elastic fibers, ranging from
      41 to 82%. Patients with angiographically severe venous hypertension tended to
      have a higher hypertrophic ratio than patients with moderate venous hypertension.
      Our observations support the clinical concept that long-standing arterial stress
      in the spinal venous circulation causes histological alterations of spinal
      vascular structure associated with the progression of venous hypertension. We
      suggested that possibly the histological parameter can be used for predicting
      neurological recovery after occlusion of the fistulas.

PMID- 16804273
TI  - Magnetic resonance imaging changes in a case of extra-pyramidal syndrome after
      acute organophosphate poisoning.
AB  - Distal symmetrical polyneuropathy and neuromuscular weakness is common
      neurological problem in recovery phase of acute organophosphate (OP) poisoning.
      Various types of extra pyramidal syndromes are uncommon sequel after OP
      poisoning. These are reported to be reversible within few weeks and
      characteristically associated with normal magnetic resonance imaging (MRI). In
      this report we are presenting a case with extra pyramidal syndrome after acute OP
      poisoning with few interesting MRI changes in striatum.

PMID- 16804275
TI  - Abscess formation in Rathke's cleft cyst.

PMID- 16804274
TI  - Giant calvarial hyperostosis with biparasagittal en plaque meningioma.
AB  - We report a patient with an uncommon presentation in the form of massive
      bilateral calvarial hyperostosis with bi-parasagittal en plaque meningioma. The
      tumour was removed by bilateral fronto-parieto-occipital craniotomies. The
      patient was subjected to post operative radiotherapy to reduce the chances of
      recurrance. The management of such a case is a surgical challenge.

PMID- 16804276
TI  - Oxcarbazepine induced hyponatremic coma.

PMID- 16804277
TI  - Guillain Barre syndrome with brisk reflexes-another variant.

PMID- 16804278
TI  - Bullet injury to the atlanto-axial region.

PMID- 16804279
TI  - Is myasthenia gravis more benign in the Indian population?

PMID- 16804280
TI  - Reversible ageusia associated with clopidogrel treatment.

PMID- 16804281
TI  - Intraoperative development of posterior fossa extradural hematoma during
      evacuation of frontal contusion.

PMID- 16804282
TI  - Supratentorial intracerebral haemorrhage following posterior fossa operation.

PMID- 16804283
TI  - Post-traumatic bilateral abducens nerve palsy.

PMID- 16804284
TI  - 'Latet anguis in herba' (Snake in the grass).

PMID- 16804285
TI  - Intracranial metallic foreign body presenting with a unique route of introduction
      into the brain.

PMID- 16804286
TI  - Persistent trigeminal artery: a rare cause of trigeminal neuralgia - MR imaging.

PMID- 16804287
TI  - Endothelial function in patients with obstructive sleep apnea syndrome but
      without hypertension.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) influences endothelial
      function and causes hypertension. OBJECTIVES: Our aim was to evaluate the role of
      endothelial dysfunction in the pathogenesis of hypertension in OSAS. METHODS:
      Twenty-three patients with OSAS but without hypertension and 15 healthy
      normotensive subjects were investigated. The presence or absence of OSAS was
      evaluated with a sleep study. Endothelial function was investigated with brachial
      artery ultrasound examination. RESULTS: Baseline characteristics were equivalent
      between the two groups. Minimal oxygen saturation and apnea-hypopnea indexes in
      the OSAS and control groups were 62.9 +/- 16.5 versus 94.9 +/- 1.1% (p < 0.0001)
      and 53.1 +/- 20.3 versus 3.8 +/- 0.9 (p < 0.0001), respectively. There was not
      statistically significant difference between basal brachial artery diameters
      measured in the morning and in the evening in all groups. Flow-mediated dilation
      (FMD) values measured in the morning were lower than those measured in the
      evening in both OSAS patients and the control group: FMD of OSAS patients was
      6.04 +/- 3.18% in the morning and 10.38 +/- 4.23% in the evening hours (p =
      0.001), and FMD of control subjects was 10.9 +/- 2.6% in the morning and 13.9 +/-
      2.32 in the evening hours (p = 0.002). Differences in FMD values measured both in
      the morning and evening hours in OSAS patients were lower compared with those in
      control subjects (p < 0.0001 in the morning hours and p = 0.003 in the evening
      hours). CONCLUSIONS: We detected a prominent diurnal deterioration in endothelial
      function in normotensive OSAS patients compared with healthy subjects. This
      deterioration may occur due to ongoing hypoxemia during the night and it may be a
      possible cause of hypertension and atherosclerotic cardiovascular diseases in
      patients with OSAS.

PMID- 16804288
TI  - Is there an ideal diagnostic algorithm in solitary pulmonary nodules?

PMID- 16804289
TI  - Effect of continuous positive airway pressure on the risk of road accidents in
      sleep apnea patients.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) reduces daytime somnolence
      in the obstructive sleep apnea syndrome (OSAS) and may contribute to a reduction
      in the risk of motor vehicle accidents. OBJECTIVE: To evaluate the effects of
      CPAP on automobile collisions in patients with OSAS. METHODS: We compared the
      number of motor vehicle accidents in 80 patients with OSAS and 80 healthy
      subjects during the 2 years before and the 2 years after study entry, at which
      CPAP treatment was initiated. RESULTS: Patients with OSAS had a 2.6 times higher
      risk of suffering an automobile collision compared to controls (rate ratio,
      RR=2.57; 95% confidence interval, CI=1.30-5.05). After 2 years of CPAP treatment,
      the rate of collisions was reduced more than half in patients with OSAS (RR=0.41;
      95% CI=0.21-0.79), but this occurred also in controls (RR=0.49; 95% CI=0.17
      1.40). The magnitude of this fall between groups was not different (p for
      interaction=0.68), even after adjusting for body mass index, alcohol intake and
      Epworth scale. CONCLUSIONS: Patients with OSAS have an increased risk of
      suffering a traffic collision. This risk was significantly reduced after their
      inclusion in the study. Yet, as this reduction also occurred in the control
      group, this effect may not be due to CPAP therapy.

PMID- 16804290
TI  - Relationship between exhaled breath condensate volume and measurements of lung
      volumes.
AB  - BACKGROUND: Exhaled breath condensate (EBC) is proving to be a technique which
      can sample markers of lung inflammation; however, many factors affect the
      collection process. OBJECTIVES: We hypothesised that lung volumes--tidal volume,
      minute volume and total lung capacity (TLC)--would dictate the volume of the EBC
      sample that could be collected. METHODS: First, the volume of EBC collected was
      measured while measuring the tidal volume and minute volume in normal, asthmatic
      and chronic obstructive pulmonary disease subjects. Second, the volume of EBC was
      compared between breathing at tidal volumes and breathing at vital capacity in
      normal subjects. TLC was measured by plethysmography. RESULTS: The mean EBC
      volume was 5.55 +/- 0.50 microl/breath in normal subjects (n = 23), 3.56 +/- 0.33
      microl/breath in chronic obstructive pulmonary disease patients (n = 25) and 5.77
      +/- 0.50 microl/breath in asthmatic subjects (n = 17). EBC volume was
      significantly correlated with both tidal volume (Pearson's r = 0.775, p < 0.0005)
      and minute volume (Pearson's r = 0.425, p < 0.0005), but importantly, EBC volume
      was not significantly affected by age, gender or disease status. There was a
      significant difference in EBC volume when tidal breathing was compared with
      breathing at vital capacity (5.55 +/- 0.50 vs. 20.59 +/- 1.72 microl; p <
      0.0001). No significant correlation was found between EBC volume and TLC (21
      normal subjects). CONCLUSIONS: These results suggest that tidal and minute volume
      can predict the amount of EBC that can be expected to be collected. No
      significant differences in the volume of EBC were seen between normal subjects
      and those with airway diseases.

PMID- 16804292
TI  - Ketoconazole-tacrolimus coadministration in kidney transplant recipients: two
      year results of a prospective randomized study.
AB  - BACKGROUND/AIMS: In developing countries, kidney transplantation is greatly
      hindered by financial problems, especially due to costly newer immunosuppressive
      medications. Ketoconazole increases blood levels of tacrolimus and cyclosporine
      through inhibition of cytochrome P450 microsomal enzymes. We previously reported
      on the 6-month safety and the outstanding impact on treatment costs of the
      ketoconazole-tacrolimus combination in kidney transplant recipients. Data of this
      combination are still lacking in the literature. We hereby report on the 2-year
      results of our trial. METHODS: This prospective, randomized study included 70
      live-donor kidney transplant recipients receiving tacrolimus (age 16-45 years, 54
      males and 16 females). Patients were randomized into two equal groups: group 1,
      where ketoconazole 100 mg/day was added, and group 2 (control group). RESULTS:
      After 2 years, group 1 (ketoconazole) patients still showed a highly significant
      reduction of the tacrolimus dose (by 53.8%) and cost (by 52.9%) compared with the
      control group (p < 0.001) and a significant improvement in graft function in
      comparison to their own initial graft function (p = 0.002). Throughout the 2
      years, no side effects of ketoconazole were noted. CONCLUSION: We conclude that
      the long-term ketoconazole-tacrolimus combination therapy in kidney transplant
      recipients during the 2 years is safe, has an outstanding impact on treatment
      costs and improves graft outcome.

PMID- 16804291
TI  - One-year evaluation of the preventative effect of hydrofluoroalkane
      beclomethasone dipropionate on eosinophilic inflammation of asthmatic peripheral
      airways.
AB  - BACKGROUND: In asthmatic patients with eosinophilic inflammation of the
      peripheral airways, appropriate drug delivery to the affected area is required.
      OBJECTIVE: It was the aim of this study to assess persistent eosinophilic
      inflammation of the peripheral airways in asthmatic patients, stabilized by the
      long-term use of dry powder type inhaled steroids, and to evaluate the clinical
      efficacy of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) over 1 year.
      METHODS: Seventy-four outpatients with moderate stable asthma were studied for at
      least 6 months, 37 treated with fluticasone propionate Diskus (FP-DK) and 37 with
      budesonide Turbuhaler (BUD-TH). The eosinophil count, eosinophil cationic protein
      (ECP), eotaxin and RANTES levels in 10% hypertonic saline-induced sputum were
      examined before treatment, as well as 4 weeks, 8 weeks, 6 months and 1 year after
      switching patients to HFA-BDP. RESULTS: Fifteen patients (40.5%) in the FP-DK
      group and 12 (32.4%) in the BUD-TH group had eosinophils in induced sputum. The
      sputum ECP in the eosinophil-positive and the eosinophil-negative groups was
      1,510.1 +/- 2,009.3 versus 426.6 +/- 464.1 microg/l (p = 0.037) in the FP-DK
      group, and 3,850.0 +/- 5,486.2 versus 492.0 +/- 1,150.7 microg/l (p = 0.011) in
      the BUD-TH group, respectively. Four weeks after the switch to HFA-BDP, the
      number of eosinophil-positive patients decreased in both groups. Significant
      reductions in sputum ECP and eotaxin were observed at 8 weeks, and their
      concentrations continued decreasing for 1 year. CONCLUSION: There is a certain
      proportion of asthmatic patients for whom long-term treatment with dry powder
      type steroids may not be suitable; however, their peripheral airway inflammation
      improved after switching them to HFA-BDP, suggesting its excellent delivery.

PMID- 16804293
TI  - Elevated levels of alkanals, alkenals and 4-HO-alkenals in plasma of hemodialysis
      patients.
AB  - BACKGROUND/AIMS: Several studies have implicated reactive carbonyl compounds
      (RCOs), especially those derived from lipid peroxidation, in the development of
      complications frequently associated with hemodialysis (HD) treatment. However,
      there is still much unknown regarding the nature and concentration of RCOs in HD
      patients. This study was designed to evaluate the level of toxic aldehydes in the
      plasma of HD patients and to determine the extent to which these aldehydes
      contribute to RCO toxicity among these patients. METHODS: 15 aldehydes of the
      alkanal, alkenal and 4-HO-alkenal type were measured in the plasma of 17 HD
      patients and 20 healthy controls. In addition, protein modification markers such
      as carbonyl content (CO), free thiol (SH) and residual free amino groups, as well
      as amyloid fibrils were also determined. RESULTS: 11 of the 15 aldehydes were
      significantly elevated in the HD group when compared with the controls.
      Correlation studies in the HD group revealed high relationships between total
      alkenals plus total 4-HO-alkenals versus CO, total alkanals versus NH2, total
      aldehydes versus SH, and total 4-HO-alkenals versus fibril. CONCLUSION: The
      increased levels of alkanals, alkenals and 4-HO-alkenals of lipid peroxidation in
      the plasma of HD patients may greatly contribute to the toxicity of RCOs. The
      pattern of modification of plasma protein by each group of aldehydes may provide
      new evidence on the in vivo mechanisms of toxicity triggered by these aldehydes
      on their target molecules.

PMID- 16804294
TI  - Hypoxia potentiates endotoxin-induced allopregnanolone concentrations in the
      newborn brain.
AB  - BACKGROUND: Allopregnanolone is a neurosteroid produced in the brain that can
      alter the excitability of the CNS. Neurosteroids have neuroprotective properties,
      and their elevation in response to stress may protect the newborn brain following
      infection or hypoxia. Infection, particularly of the respiratory tract, may lead
      to episodes of hypoxia. Infection and hypoxia have been identified as factors
      contributing to neonatal morbidity and mortality. OBJECTIVES: To determine the
      effect of acute episodes of hypoxia alone or in combination with
      lipopolysaccharide (LPS) exposure on plasma and brain allopregnanolone
      concentrations in lambs 10-21 days old. Also, to examine plasma levels of
      cortisol and the cytokines, tumour necrosis factor-alpha and interleutkin-6 after
      these challenges. RESULTS: Allopregnanolone concentrations in the brain were
      markedly increased after hypoxia. Hypoxia following prior LPS treatment resulted
      in greater increases in brain allopregnanolone concentrations compared to either
      the LPS or hypoxia treatment alone. Importantly, brain regions unaffected by LPS
      or hypoxia alone (thalamus/hypothalamus, cerebellum) showed significant increases
      of allopregnanolone content following the combined LPS and hypoxia treatments.
      Plasma tumour necrosis factor-alpha and interleukin-6 concentrations were
      increased after LPS treatment with and without hypoxia, but not by hypoxia alone.
      In contrast, plasma cortisol concentrations were increased after both stressors.
      CONCLUSIONS: These results show that the brain of young lambs readily responds to
      physiological stress by increased production of allopregnanolone. This response
      may protect the developing brain from the cytotoxicity following hypoxic and
      infectious episodes.

PMID- 16804295
TI  - Cardiomyopathy related to antimalarial therapy with illustrative case report.
AB  - The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) are used
      in long-term treatment of connective tissue diseases and dermatological disorders
      and are generally regarded as safe. We present one case of cardiotoxicity in a 59
      year-old woman treated with antimalarials during 13 years for a discoid lupus
      erythematosus. She progressively developed conduction disturbances and congestive
      heart failure (CHF). When the diagnosis of antimalarials toxicity was suspected,
      CQ was withdrawn. However, heart transplantation had to be performed in the
      following 4 months for severe CHF. Indeed, rare but severe cardiotoxicity may
      develop following prolonged use of antimalarials with both conduction
      disturbances (45 patients) and CHF (25 patients). These cardiac toxic effects
      have been reported with CQ and less frequently with HCQ use alone. Diagnoses are
      often delayed since the toxicity of the drug might be misattributed to other
      factors in these patients. The endomyocardial biopsy, or in some cases the muscle
      biopsy, are essential to confirm the antimalarials toxicity. Antimalarials have
      been stopped in 12 cases of CHF, leading to improvement in 8 cases (within 3
      months to 5 years) and to deaths or to heart transplantation in 4 cases (within 1
      week to 3 months). In the latter cases, as in our patient, the lack of
      improvement may have been explained by the severity of the cardiomyopathy at
      diagnosis and the short delay since withdrawal. As a consequence, the potential
      for reversibility and the severity in undiagnosed cases of these toxic
      cardiomyopathies emphasize the importance of recognizing early signs of toxicity
      in order to withdraw antimalarials before the occurrence of life-threatening CHF.

PMID- 16804296
TI  - Cardiac arrest and ventricular tachycardia in Japanese-type apical hypertrophic
      cardiomyopathy.
AB  - Apical hypertrophic cardiomyopathy (HCM) is a specific variant of HCM. This
      disease has been first described in Japan where the prevalence is much higher
      than in the western world. The prognosis of apical HCM with regard to sudden
      cardiac death is believed to be better than that of common HCM. We present,
      however, two male caucasian patients with apical HCM and malignant arrhythmias.
      Both patients had marked apical hypertrophy on echocardiography, 'giant' negative
      T-waves on the ECG and spade-like configuration of the left ventricle on
      angiography. The first patient had been successfully recussitated from cardiac
      arrest at the age of 52 years. The second patient had a syncope at the age of 42
      years and had non-sustained ventricular tachycardia. In both cases, a
      cardioverter-defibrillator was implanted and treatment with verapamil was
      initiated. These observations suggest that the risk of sudden cardiac death might
      be increased not only in common HCM, but also in Japanese-type apical HCM.

PMID- 16804297
TI  - Effects of electromagnetic fields on cells: physiological and therapeutical
      approaches and molecular mechanisms of interaction. A review.
AB  - This review concentrates on findings described in the recent literature on the
      response of cells and tissues to electromagnetic fields (EMF). Models of the
      causal interaction between different forms of EMF and ions or biomolecules of the
      cell will be presented together with our own results in cell surface recognition.
      Naturally occurring electric fields are not only important for cell-surface
      interactions but are also pivotal for the normal development of the organism and
      its physiological functions. A further goal of this review is to bridge the gap
      between recent cell biological studies (which, indeed, show new data of EMF
      actions) and aspects of EMF-based therapy, e.g., in wounds and bone fractures.

PMID- 16804298
TI  - Particle size of hydroxyapatite granules calcified from red algae affects the
      osteogenic potential of human mesenchymal stem cells in vitro.
AB  - Hydroxyapatite (HA) microparticles as a carrier in an injectable tissue
      engineered bone filler are considered promising candidates for the treatment of
      small bone defects in the craniomaxillofacial region. HA granules calcified from
      red algae, varying in size, were evaluated in vitro for their suitability to be
      used as a carrier for human mesenchymal stem cells (hMSCs). Three groups of
      granules were produced in grain sizes of 10-100, 200-500 and 600-1,000 mum. After
      seeding and culturing hMSCs under osteogenic differentiation conditions onto HA
      particles for 3, 6 and 9 days, cellular proliferation (tetrazolium salt, XTT),
      alkaline phosphatase (ALP)-specific activity and total protein synthesis were
      investigated. The osteoblastic phenotype of the cells was evaluated by assaying
      the bone-specific genes osteocalcin, osteopontin and collagen type I. XTT assay
      revealed significantly higher (p < 0.01) proliferation of cells grown on the
      smallest grain size after 9 days of culture. Regarding ALP-specific activity,
      significantly higher levels of activity were detected in cells grown on the
      smallest grain size. Different grain sizes had no significant effects on the
      secretion of osteocalcin and osteopontin. Collagen type I production was
      significantly higher (p < 0.05) in cells grown on the biggest grain size in
      comparison with the two other grain sizes. These results show that the particle
      size of HA microparticles affects the osteogenic potential of cultured hMSCs and
      lead to the conclusion that particle size has differential effects on ALP
      specific activity and collagen type I production.

PMID- 16804299
TI  - Morphology and function of ovine articular cartilage chondrocytes in 3-d hydrogel
      culture.
AB  - Different cell- and biomaterial-based tissue engineering techniques are under
      investigation to restore damaged tissue. Strategies that use chondrogenic cells
      or tissues in combination with bioresorbable delivery materials are considered to
      be suitable to regenerate bio-artificial cartilage. Three-dimensional (3-D) cell
      embedding techniques can provide anchorage-independent cell growth and homogenous
      spatial cell arrangement, which play a key role in the maintenance of the
      characteristic phenotype and thus the formation of differentiated tissue. We
      developed a new injectable high water content (90%) hydrogel formulation with 5%
      sodium alginic acid and 5% gelatin as a temporary supportive intercellular matrix
      for 3-D cell culture. The objective was to determine whether the in vitro
      hydrogel culture of chondrocytes could preserve hyaline characteristics and thus
      could provide cartilage regeneration in vitro. Chondrocytes harvested from knee
      joints of skeletally mature sheep were cultured 3-D in hydrogel (7 x 10(6)
      cells/ml, 2.8-mul beads) for up to 10 weeks. Cell morphology and viability were
      evaluated with light microscopy, and proliferative activity was assessed with
      antibromodeoxyuridine immunofluorescence. Expression of collagens type I (COL1)
      and II (COL2), cartilage proteoglycans (PG) and hyaluronan synthases (HAS) were
      studied immunohistochemically. We observed that up to 36% of chondrocytes
      proliferated, while almost 100% presented a differentiated spheroidal phenotype.
      After an initial decrease at 2 weeks, cell density recovered to 85% of the
      initial absolute value at 10 weeks. Expression of hyaline matrix molecules
      resembled the in vivo pattern with increasing spatial deposition of PG and COL2.
      The proportion of PG-positive cells increased from initially 13 to 53% after 10
      weeks, in contrast to consistently 100% COL2-positive cells. We conclude that 3-D
      hydrogel culture, even without mechanical stimulation or growth factor
      application, can keep chondrocytes in a differentiated state and provides a
      chondrogenic cell environment for in vitro cartilage regeneration for at least 10
      weeks. Moreover, this hydrogel appears to be a suitable cell delivery material
      for subsequent in vivo implantation.

PMID- 16804300
TI  - Effects of epidermal growth factor and keratinocyte growth factor on the growth
      of oropharyngeal keratinocytes in coculture with autologous fibroblasts in a
      three-dimensional matrix.
AB  - Tissue engineering of oropharyngeal mucosa is rendered complex by the fact that
      oropharyngeal keratinocytes are difficult to culture in the long term and do not
      grow well after several subcultivations. Three populations of oropharyngeal
      keratinocytes were isolated by a method based on different levels of beta(1)
      integrin expression. In particular, keratinocytes were isolated between cell
      fractions that adhere rapidly on collagen-IV-coated culture dishes (RAC-IV) and
      populations that are less adherent (RAC-IV-D). The total fraction of both
      subpopulations served as a control (RAC-IV-T). The epidermal growth factor (EGF)
      and the keratinocyte growth factor (KGF) were examined with regard to their
      effects on the growth of the three populations. Growth curves of all three cell
      fractions grown with or without EGF were generated, and different concentrations
      of EGF and KGF were tested. EGF did not change any growth characteristics of the
      cells, with the exception of the speed of growth. Best growth was achieved with a
      physiologic EGF concentration of 0.15-1.5 ng/ml and a KGF concentration of 15
      ng/ml. Finally, we cocultured oropharyngeal keratinocytes and their autologous
      fibroblasts in a three-dimensional matrix using Matrigeltrade mark. Oropharyngeal
      keratinocytes grown in coculture formed larger colonies than keratinocytes grown
      without fibroblasts. In conclusion, we were able to optimize the supplement of
      EGF and KGF in standard medium for the long-term culture of primary oropharyngeal
      keratinocytes. The use of Matrigel as a scaffold for three-dimensional cocultures
      of oropharyngeal keratinocytes and fibroblasts might signify a step forward in
      the development of a transplantable mucosa construct.

PMID- 16804301
TI  - Renal Angiotensin receptor type 1 and 2 upregulation in intrauterine growth
      restriction of newborn piglets.
AB  - Epidemiological and experimental studies suggest that intrauterine growth
      restriction (IUGR) is associated with abnormalities in kidney development which
      is thought to be linked with alterations causing adult cardiovascular diseases.
      The renin-angiotensin system (RAS) plays an important role in the development of
      renal vascular and tubular structures, and is known to be altered by
      experimentally induced IUGR. These experimental models of IGUR have been
      criticized because they may have a more severe impact on intrauterine development
      than that which is normally encountered in humans. Therefore, we asked whether
      naturally occurring small-for-gestational-age newborn piglets exhibit features of
      altered RAS activity. We investigated the regional renal expression of
      angiotensin II type 1 (AT1) and AT2 receptors in normal-weight and IUGR piglets.
      The AT1 receptor mRNA expression was markedly enhanced in IUGR piglets, in the
      renal cortex by 64% and in the renal medulla by 52% (p < 0.05, compared with
      normal littermates). In contrast, mRNA expression for the AT2 receptor was
      similar in both the normal-weight and IUGR piglets. A significantly higher AT1
      receptor protein expression was found in the IUGR piglets (p < 0.05) in the
      glomeruli, in the proximal and distal tubules, as well as in the collecting ducts
      by immunohistochemistry. Furthermore, AT2 receptor protein expression was
      significantly higher in the IUGR piglets (p < 0.05) in the subcapsular
      nephrogenic zone and in the distal tubules and collecting ducts. Thus, IUGR is
      accompanied by an upregulation of angiotensin II receptor expression in the
      kidneys of newborn piglets. This may indicate an alteration of the RAS in
      newborns suffering from naturally occurring IUGR.

PMID- 16804302
TI  - Oral but not parenteral aspirin upregulates COX-2 expression in rat stomachs. a
      relationship between COX-2 expression and PG deficiency.
AB  - AIM: We compared the ulcerogenic effects of aspirin (ASA) and indomethacin in the
      rat gastric mucosa depending on the route of administration, together with the
      expression of COX-2. METHODS: Animals fasted for 18 h were given ASA or
      indomethacin, either p.o. or s.c., and the stomach was examined 4 h later.
      RESULTS: Indomethacin decreased mucosal PGE(2 )level, increased gastric motility,
      and caused gastric lesions with the up-regulation of COX-2 expression,
      irrespective of the route of administration. ASA induced both damage and COX-2
      expression in the stomach when given p.o. but not s.c., despite decreasing the
      PGE(2) level similarly via either route of administration. Gastric motility was
      temporarily increased and gastric potential difference (PD) was markedly
      decreased by ASA given p.o. PGE(2) and atropine, although preventing ASA-induced
      gastric lesions as well as hypermotility, affected neither the COX-2 expression
      nor PD reduction induced by p.o. ASA. By contrast, the COX-2 expression induced
      by indomethacin was prevented by both PGE(2) and atropine. CONCLUSION: ASA given
      p.o. caused damage in the stomach, together with the up-regulation of COX-2
      expression, and this expression may be due to the topical irritative action,
      rather than being a result of PG deficiency. The expression of COX-2 after
      indomethacin is associated with gastric hypermotility due to PG deficiency.

PMID- 16804304
TI  - Predictors of intra- and postoperative complications in laparoscopic colorectal
      surgery: results of an expert survey.
AB  - BACKGROUND: The decision which patient should undergo laparoscopic rather than
      open colorectal surgery depends on weighing its benefits against its
      complications. We explored which criteria prognosticate complications in a
      laparoscopic intervention by assembling experienced visceral surgeons' beliefs.
      METHODS: A two-round postal survey was conducted: 21 experts in laparoscopic
      surgery were contacted and asked to list (first round) and weigh (second round)
      indicators (scale 1-10) they believed predicted intra- or postoperative
      complications in patients undergoing laparoscopic colorectal surgery. Median
      ratings and interquartile ranges (IQRs) were calculated. Rates >or=6 and IQRs
      <or=3 depicted an important prognostic indicator for complications. RESULTS:
      Thirty-nine intraoperative and 43 postoperative listings and ratings of 19
      experts (90%) were available for analysis. The experts depicted three domains of
      indicators (tumor, comorbidity and related institution). The strongest indicators
      for intraoperative complications were surgeon's experience (median 9, IQR 8-10)
      and portal hypertension (median 9, IQR 7-10), and those for postoperative
      complications were liver cirrhosis Child B/C (median 8, IQR 7.75-10) and
      experience of the surgeon (median 8, IQR 7-10). CONCLUSION: This survey provides
      additional evidence of risk indicators for intra- and postoperative complications
      in patients undergoing laparoscopic colorectal surgery. Whether the identified
      indicators can be compiled into a prognostic instrument requires confirmation in
      a properly designed and sized study.

PMID- 16804303
TI  - Relationship of underlying abnormalities in rectal sensitivity and compliance to
      distension with symptoms in irritable bowel syndrome.
AB  - BACKGROUND/AIMS: Abnormalities in rectal physiology play an important role in the
      genesis of symptoms in irritable bowel syndrome (IBS). However, their
      relationship to symptoms is unclear. Our aim was to investigate the association
      of abnormalities in rectal sensitivity and compliance to specific symptoms in
      IBS. METHODS: Fifty-six IBS patients and 14 healthy controls participated in this
      study. The intensities of individual IBS symptoms in the past 4 weeks were scored
      on a graded 5-point Likert scale. Using a barostat, isobaric rectal distensions
      were performed before and after a meal. RESULTS: Rectal hypersensitivity and
      hypocompliance in the fasting state were observed in 68 and 52% of IBS patients,
      respectively. Postprandial hypersensitivity of the rectum was significantly more
      prevalent in the diarrhea-predominant IBS (D-IBS) group compared to the
      constipation-predominant IBS (C-IBS) group. The D-IBS group showed a significant
      postprandial decrease in rectal compliance, but the C-IBS group did not. A
      significant correlation was observed between a sense of incomplete evacuation and
      increased bowel movements with postprandial rectal hypersensitivity or
      hypocompliance. CONCLUSION: A sense of incomplete evacuation and increased bowel
      movements are related to postprandial abnormalities in rectal sensitivity and
      compliance to distension. The other IBS symptoms do not seem to predict such
      abnormalities.

PMID- 16804305
TI  - Mechanical bowel obstruction due to an impacted gallstone.

PMID- 16804306
TI  - Radiofrequency sinus excision.

PMID- 16804308
TI  - Uncinatectomy: a novel surgical option for the management of intraductal
      papillary mucinous tumors of the pancreas.
AB  - An intraductal papillary mucinous tumor (IPMT) is a rare cystic lesion of the
      pancreas, comprising only 1% of all pancreatic exocrine neoplasms. The prognosis
      for these lesions is typically favorable as compared with invasive ductal
      carcinomas. Nevertheless, the management of IPMTs involves surgical resection due
      to their malignant potential. When located in the pancreatic head, the
      conventional treatment for IPMT is pancreatoduodenectomy. Some authors have
      advocated limited pancreatectomy for low-grade IPMTs of the pancreas, thereby
      decreasing the morbidity of more extensive resection. In this report, we describe
      our technique of minimal pancreatectomy, whereby the uncinate process and
      associated branch duct were completely extirpated while preserving remainder of
      the pancreatic head, duodenum, and pancreatic ducts. The case presented
      underscores the feasibility and advantages of minimal pancreatic resection in the
      management of such tumors.

PMID- 16804307
TI  - In situ graft-trimming method using polyester vascular prosthesis for inferior
      vena cava reconstruction after hepatectomy.
AB  - Hepatectomy for secondary liver cancer that has invaded the inferior vena cava
      (IVC) can be the only way to achieve long-term survival. We describe a method for
      hepatectomy combined with partial IVC resection without venous bypass circulation
      and an in situ graft-trimming method to avoid graft size mismatch after
      reconstruction. We carried out left hepatectomy extended to segment 1 with
      partial IVC resection first. During resection and reconstruction of the IVC, it
      was clamped below the right hepatic vein and above the inferior right hepatic
      vein to maintain systemic circulation. The graft was trimmed in situ, after a
      half running suture of the graft was finished to ensure the correct size.
      Preservation of both inferior right hepatic vein and right hepatic vein helps to
      maintain systemic circulation during reconstruction of the IVC. The in situ graft
      trimming method is an easy and safe method to ensure the correct graft size after
      IVC reconstruction.

PMID- 16804309
TI  - Facioscapulohumeral muscular dystrophy and occurrence of heart arrhythmia.
AB  - BACKGROUND: Subjects with facioscapulohumeral muscular dystrophy (FSHD) do not
      generally suffer from significant cardiac symptoms. Although with heterogeneous
      results, studies reported to date indicate that heart alterations unrelated to
      cardiomyopathy are possible in FSHD. PATIENTS AND METHODS: We describe the
      findings of a multicenter investigation aimed at detecting cardiac abnormalities
      in 83 FSHD patients, 44 males and 39 females with a mean age of 47 years. All
      patients underwent clinical heart examination, 12-lead electrocardiography and 24
      hour Holter monitoring; echocardiography was also performed on most patients.
      RESULTS: Among the 83 patients, 62 with no cardiovascular risk factors were
      identified. Ten of them manifested clinical or subclinical cardiac involvement: 5
      reported symptoms represented mostly by frequent palpitations secondary to
      supraventricular arrhythmia and another 5 exhibited electrocardiographic signs of
      short runs of supraventricular paroxysmal tachycardia. In the absence of
      cardiovascular risk factors, we found symptoms or signs of heart involvement of
      mainly arrhythmic origin in 10 of our 83 FSHD patients (12%). CONCLUSIONS:
      Considering our data and those available in the literature as a whole, arrhythmic
      alterations seem to be detected more frequently than expected in FSHD patients.

PMID- 16804310
TI  - Impact of female gender on prognosis in type 2 diabetic patients with ischemic
      stroke.
AB  - This study assessed gender differences in diabetic patients with ischemic stroke
      with respect to vascular risk factors, clinical features and early outcome.
      Ischemic stroke was diagnosed in 261 diabetic women and 300 diabetic men of 2,446
      ischemic stroke patients included in a prospective stroke registry over 17 years.
      Mean +/- SD age was 77.5 +/- 8.3 years in women and 71.8 +/- 9.7 years in men (p
      < 0.021). Risk factors for stroke including hypertension, atrial fibrillation,
      congestive heart failure and valvular heart disease were significantly more
      common in women. Cardioembolic infarction occurred in 29.5% of women and 15.3% of
      men (p < 0.001), and lacunar stroke in 40.3% of men and 29.9% of women (p <
      0.006). In-hospital mortality was 14.9% in diabetic women, and 8.3% in diabetic
      men (p < 0.02). After multivariate analysis, congestive heart failure (OR =
      4.59), frontal lobe involvement (OR = 2.67), hypertension (OR = 1.62) and age
      were independent variables for ischemic stroke in diabetic women. Diabetic women
      had a poor prognosis, which may be due to differences in age, comorbidity and
      stroke subtype distribution.

PMID- 16804311
TI  - Effect of vitamin A on the CD44 expression in the small intestine of rats with
      obstructive jaundice.
AB  - HYPOTHESIS: In this study, the influence of obstructive jaundice on the CD44
      expression in the rat small intestine and the alterations of this CD44 expression
      by vitamin A given intraperitoneally (200 IU/g/day) are evaluated. MATERIALS AND
      METHODS: In a prospective animal model study, 32 Sprague-Dawley rats were
      randomized into four groups: group A rats (n = 8) underwent sham operation and
      were given daily saline intraperitoneally for 2 weeks (sham + saline); group B
      animals (n = 8) underwent sham operation and were given daily vitamin A
      intraperitoneally for 2 weeks (sham + vitamin A); group C rats (n = 8) underwent
      common bile duct ligation and were given daily saline intraperitoneally for 2
      weeks (obstructive jaundice + saline), and group D animals (n = 8) underwent
      common bile duct ligation and were given daily vitamin A intraperitoneally for 2
      weeks (obstructive jaundice + vitamin A). After 2 weeks, standardized jejunum and
      ileum segments were harvested from all animals. The expression of CD44 on the
      cell surface was evaluated immunohistochemically. Comparisons among the four
      groups were done. RESULTS: The plasma bilirubin, aspartate transaminase, alanine
      transaminase, alkaline phospatase, and gamma-glutamyltransferase levels in groups
      C and D (obstructive jaundice groups) were higher than those in groups A and B
      (sham groups; p < 0.05). There was no difference between groups A and B (sham
      groups) with regard to the number of cells expressing surface CD44 in jejunum and
      ileum. When groups A and B were compared with group C (obstructive jaundice +
      saline) animals, the number of cells expressing surface CD44 was significantly
      decreased in both jejunum and ileum in group C. The difference between sham
      groups (A and B) and group C was found to be significant (p < 0.05). When group D
      (obstructive jaundice + vitamin A) was compared with group C (obstructive
      jaundice + saline), the number of cells expressing surface CD44 was significantly
      increased in jejunum and ileum in group D animals (p < 0.05), higher than in the
      sham groups (A and B). The difference between group D and sham groups (A and B)
      was found to be significant (p < 0.05). CONCLUSION: Obstructive jaundice for 2
      weeks significantly decreased the CD44 expression in the rat small intestine. We
      found that daily intraperitoneal administration of vitamin A in rats with
      obstructive jaundice for 2 weeks significantly restored the impaired CD44
      expression.

PMID- 16804313
TI  - Ovarian cancer associated with testosterone supplementation in a female-to-male
      transsexual patient.
AB  - Ovarian cancer is the most fatal gynecologic malignancy. Women often present late
      and though median survival has improved, a majority of women will succumb to
      their disease. The incidence of ovarian cancer among female-to-male transsexuals
      is not known. We report only the second case of ovarian cancer in a female-to
      male transsexual while on androgen supplementation therapy. Staining of his tumor
      for androgen receptors showed abundant expression. Androgen supplementation in
      this population may be associated with an increased risk of both ovarian cancer
      and of endometrial cancer. Consideration for bilateral salpingo-oophorectomy as
      part of gender reassignment surgery should be given, especially in this poorly
      studied group of patients whose overall risk of ovarian cancer remains unknown.

PMID- 16804312
TI  - Effects of unfractionated heparin and low-molecular-weight heparin on colonic
      anastomoses in the presence of experimental peritonitis.
AB  - BACKGROUND: We aimed at investigating the effects of unfractionated heparin (UFH)
      and low-molecular-weight heparin (LMWH) on the healing process of colonic
      anastomoses in the presence of peritonitis which is known to adversely affect the
      healing process. STUDY DESIGN: Three groups of Wistar albino rats (n = 15 in each
      group) with experimental fecal peritonitis were studied. A 1-cm colonic segment
      was resected, and an end-to-end anastomosis was performed. The control group
      (group 1) was given no treatment; group 2 animals received 50 IU/kg s.c. UFH
      twice a day, and group 3 rats received LMWH at a dose of 1.5 mg/kg daily for 7
      days postoperatively. Relaparotomy was done on day 7 in the surviving rats. The
      rats were sacrificed by resection of the colonic segment. The anastomosis
      bursting pressures were measured and the tissue samples from anastomosis lines
      were histopathologically examined. RESULTS: The bursting pressures were
      significantly higher in UFH and LMWH groups as compared with the controls (p =
      0.021 and p < 0.001, respectively), while there was no statistically significant
      difference between UFH and LMWH groups. Positive bacterial culture results were
      more common in controls (90%) than in the other two groups (p = 0.029 and p =
      0.002, respectively). Also the polymorphonuclear leukocyte counts were higher (p
      = 0.005) and the fibrin formation more common (p = 0.007) in the controls. On the
      other hand, the number of fibroblasts was higher (p = 0.002) and collagen
      formation and revascularization more frequent (p = 0.001 and p = 0.001,
      respectively) in the UFH and LMWH groups. CONCLUSION: UFH and LMWH may have
      positive effects on the healing process of colonic anastomoses in the presence of
      peritonitis.

PMID- 16804314
TI  - Does the rare A172G mutation of PTPN11 gene convey a mild Noonan syndrome
      phenotype?
AB  - BACKGROUND: Noonan syndrome NS (OMIM 163950) is an autosomal dominant
      developmental disorder characterized mainly by typical facial dysmorphism, growth
      retardation and variable congenital heart defects. In unrelated individuals with
      sporadic or familial NS, heterozygous missense point mutations in the gene PTPN11
      (OMIM 176876) have been confirmed, with a clustering of mutations in exons 3 and
      8, the mutation A922G Asn308Asp accounting for nearly 25% of cases. PATIENT AND
      METHODS: We report a 7-year-old boy with short stature and some other clinical
      features of NS, who has been investigated by molecular analysis for the presence
      of mutations in the PTPN11 gene. RESULT: The de novo mutation A172G in the exon 3
      of the PTPN11 gene, predicting an Asn58Asp substitution, has been found. To the
      best of our knowledge, this specific mutation has only been described once
      before, but this is the first report of detailed clinical data suggesting a mild
      phenotype. CONCLUSION: Detailed clinical phenotype in every patient with major or
      minor features of NS and molecular identification of PTPN11 gene mutation may
      contribute to a better phenotype-genotype correlation.

PMID- 16804315
TI  - The sertoli cell--a hormonal target and 'super' nurse for germ cells that
      determines testicular size.
AB  - The somatic Sertoli cell plays an essential role in embryonic determination of
      male somatic sex and in spermatogenesis during adult life. One individual Sertoli
      cell supplies a clone of developing germ cells with nutrients and growth factors
      and it is well established that the number of Sertoli cells present is closely
      correlated to both testicular size and sperm output. Sertoli cells continue to
      proliferate and differentiate until the beginning of puberty, when they cease
      dividing and start nursing the germ cells. At this point in time, the future
      capacity of the testis for sperm production has thus been determined. Prior to
      puberty the Sertoli cells are immature and differ considerably with respect to
      morphology and biochemical activity from the mature cell. The several
      investigations that have focused on hormonal and paracrine regulation of the
      functions of the mature cell are reviewed here, but the mechanisms underlying the
      maturation and general maintenance of well-functioning Sertoli cells remain
      obscure. An alarming decline in male reproductive health has been observed in
      several Western countries during recent decades. Disturbance of Sertoli cell
      differentiation is thought to be involved in the pathogenesis of both a poor
      sperm count and testicular cancer. It is speculated that environmental agents
      that disrupt the estrogenic/androgenic balance in the testis may play a role in
      this connection.

PMID- 16804316
TI  - Central application of IGF-1 postpones time of vaginal opening in normally fed,
      but not in food-restricted rats.
AB  - BACKGROUND/AIMS: Central but also peripheral IGF-1 is suggested to play a role in
      the initiation of puberty as it directly affects GnRH synthesis and release. A
      possible intermediate in the effects of IGF-1 on puberty might be the adiposity
      signaling hormone leptin, whose plasma levels are decreased in food-restricted
      (FR) rats. METHODS: IGF-1 was chronically centrally infused in 23-day-old
      prepubertal female rats which were either normally fed or 30% FR, and the effects
      on time of vaginal opening (VO) and plasma leptin levels were monitored. RESULTS:
      FR treatment postponed time of VO and decreased plasma leptin levels. In normally
      fed rats centrally infused with IGF-1, time of VO was found to be postponed to
      the same extent as FR treatment did. The IGF-1 infusion did not affect plasma
      leptin levels in normally fed animals but increased leptin levels in the FR group
      compared to controls. Daily food intake was equal between all groups but body
      weight course was lower in FR rats. IGF-1 treatment did not significantly affect
      food intake or body weight course. CONCLUSION: FR treatment delays the moment of
      vaginal opening to the same extent as observed in normally fed rats that were
      centrally infused with IGF-1.

PMID- 16804318
TI  - An unusual patient with hypercalciuria, recurrent nephrolithiasis, hypomagnesemia
      and G227R mutation of Paracellin-1. An unusual patient with hypercalciuria and
      hypomagnesemia unresponsive to thiazide diuretics.
AB  - A 19-year-old female patient with hypercalciuria and recurrent
      nephrolithiasis/urinary tract infection unresponsive to thiazide type diuretics
      is presented. The patient first experienced nephrolithiasis at the age of 4
      years. Afterwards, recurrent passages of stones and urinary tract infection
      occurred. On diagnostic evaluation at the age of 19 years, she also had
      hypocitraturia and hypomagnesemia. Her serum calcium concentrations were near the
      lower limit of normal (8.5-8.8 mg/dl; normal range: 8.5-10.5), her serum
      magnesium concentrations were 1.15-1.24 mg/dl (normal range: 1.4-2.5) and urinary
      calcium excretion was 900 mg/24 h. PTH concentrations were increased (110-156
      pg/ml; normal range: 10-65). We tried to treat the patient with
      hydrochlorothiazide at a dose of 50 mg/day. During treatment with thiazide
      diuretics, PTH concentration remained high and the patient had recurrent urinary
      tract infections and passages of stones. Serum magnesium concentration did not
      normalize even under the parenteral magnesium infusion. Her mother had a history
      of nephrolithiasis 20 years ago. Severe hypomagnesemia in association with
      hypercalciuria/urinary stones is reported as a rare autosomal recessive disorder
      caused by impaired reabsorption of magnesium and calcium in the thick assending
      limp of Henle's loop. Recent studies showed that mutations in the CLDN16 gene
      encoding paracellin-1 cause the disorder. In exon 4, a homozygous nucleotide
      exchange (G679C) was identified for the patient. This results in a point mutation
      at position Glycine227, which is replaced by an Arginine residue (G227R). The
      mother was heterozygous for this mutation. G227 is located in the fourth
      transmembrane domain and is highly conserved in the claudin gene family. This
      case indicates the pathogenetic role of paracellin-1 mutation in familial
      hypomagnesemia with hypercalciuria and nephrocalcinosis and further underlines
      the risk of stone formation in heterozygous mutation carriers.

PMID- 16804317
TI  - Analysis of bone mineral density and turnover in patients with cystic fibrosis:
      associations between the IGF system and inflammatory cytokines.
AB  - BACKGROUND: Cystic fibrosis (CF) patients present an increased risk of
      osteoporosis, and increased fracture rate. Several factors have been identified
      as modulators of bone metabolism and bone mineral density (BMD). AIMS: To
      evaluate BMD and serum markers of bone turnover and establish their relationships
      with serum concentrations of interleukin (IL)-1beta, IL-6, tumour necrosis factor
      (TNF)-alpha, IGF-I, IGF-II, IGF binding protein (IGFBP)-2, IGFBP-3, and
      parathyroid hormone (PTH) in young adult CF patients. METHODS: Seventeen young
      adult CF patients (4 M, 13 F; mean age: 26.6 +/- 1.1 years) were enrolled in the
      study and analysed as a whole and as two subgroups according to the Shwachman
      Kulczycki score. BMD was assessed at the lumbar spine (L1-L4) by dual energy X
      ray absorptiometry (DXA Hologic QDR 2000). Bone turnover was assessed by
      measuring serum levels of osteocalcin (OC) and serum carboxyterminal propeptide
      of type I collagen (PICP) as markers of bone formation, and serum cross-linked
      carboxyterminal telopeptide of type I collagen (ICTP) as a marker of bone
      resorption. Serum IGFs, IGFBPs, and cytokines were assayed using special
      commercial kits. Daily calcium intake and weekly physical activity were estimated
      by questionnaires. Forced expiratory volume in one second was used to assess
      pulmonary function. RESULTS: Lumbar BMD was normal, although there was a tendency
      to be lower in the patients with a lower clinical score. Both OC and PICP were
      increased, whereas ICTP was normal. Lumbar BMD was positively correlated with
      pulmonary function. IL-6 and C-reactive protein (markers of inflammation) were
      inversely correlated with PICP. Serum ICTP levels were correlated with serum IGF
      I levels. No significant relationship was detected among lumbar BMD, markers of
      bone turnover and PTH, IGF-I, IGF-II, IGFBP-2, IGFBP-3, TNF-alpha, IL-1beta, and
      body mass index Z-score. CONCLUSIONS: Bone turnover is abnormal in CF patients.
      Young adult CF patients with satisfying clinical status and nutritional
      conditions have normal BMD and increased serum OC and PICP levels.

PMID- 16804319
TI  - Chemokines and chemokine receptors in scleroderma.
AB  - Scleroderma is a connective tissue disease with unknown etiology characterized by
      excessive deposition of extracellular matrix in the skin. Cellular infiltrates of
      certain immune cells and proinflammatory mediators are suggested to play a
      crucial role in cutaneous fibrosis, forming complicated networks between
      fibroblasts and immune cells via cell-cell communications. Tissue-selective
      trafficking of leukocytes is mediated by combinations of adhesion molecules and
      chemokines. Recent studies have shown that an increase in proinflammatory
      chemokines has been associated with the initiation and/or development of skin
      fibrosis/sclerosis, suggesting that chemokines and their receptors may be
      important mediators of inflammation and fibrosis in scleroderma. This review will
      focus on the roles of chemokines and their receptors during the process of
      cutaneous sclerosis and will also provide a current insight into the potential
      mechanisms of scleroderma.

PMID- 16804320
TI  - Investigations on the involvement of the lectin pathway of complement activation
      in anaphylaxis.
AB  - BACKGROUND: Systemic anaphylaxis is the most severe form of immediate
      hypersensitivity reaction. The activation of the complement system occurs during
      anaphylactic shock. The purpose of this study was to determine in a mouse model
      whether the lectin pathway of complement activation is involved in anaphylaxis.
      METHODS: To see whether the lectin pathway is involved in anaphylactic shock,
      serum mannan-binding lectin (MBL) levels were measured after passive anaphylaxis.
      Also MBL expression and binding to potential ligands were investigated. To
      determine whether complement or mast cell activation is essential for hypothermia
      in anaphylactic shock, mouse strains deficient in MBL-A and MBL-C, C1q, factors B
      and C2, C5, C5aR, or mast cells were tested. RESULTS: After antigenic challenge a
      marked drop in body temperature as well as a rapid decrease in serum MBL levels
      were observed. The decrease of serum MBL levels in shock could not be attributed
      to MBL binding to immune complexes or tissues, but an interaction of MBL with
      mast cell-derived proteoglycans was seen. In contrast to mast cell-deficient
      mice, none of the complement-deficient mouse strains were protected from shock
      associated hypothermia. CONCLUSIONS: These results indicate that neither MBL nor
      activation of the complement cascade is crucial for the induction of anaphylaxis.
      In contrast mast cell activation is associated with the development of
      hypothermia and possibly the observed decrease in serum MBL levels.

PMID- 16804321
TI  - Delayed allergic reaction to suxamethonium driven by oligoclonal Th1-skewed
      CD4+CCR4+IFN-gamma+ memory T cells.
AB  - BACKGROUND: Muscle relaxants represent the drugs most frequently involved in
      intraoperative anaphylaxis during surgical procedures. Our aim was to report the
      case of a delayed reaction to suxamethonium and analyze specific T cell lines
      with regard to their specificity, phenotype and cytokine profile. METHODS: We
      generated a drug-specific T cell line from a biopsy at the site of positive
      intradermal reactions and analyzed the immunophenotype, T cell receptor Vbeta
      domain expression and cytokine profile. RESULTS: T cells isolated from positive
      intradermal test reactions to suxamethonium showed a strict dose-dependent
      proliferation in response to drug-pulsed autologous antigen-presenting cells. The
      drug-specific CD4+ T cells were oligoclonal memory CD3+CD4+ T cells and expressed
      the skin homing receptors cutaneous lymphocyte antigen (CLA) and CCR4.
      Furthermore CD4+ suxamethonium-reactive T cell lines were IFN-gamma-positive and
      synthesized high levels of IFN-gamma and TNF-alpha. CONCLUSION: The study
      describes a delayed hypersensitivity to suxamethonium, driven by an oligoclonal T
      helper cell 1-skewed CD4+ memory T cell population, expressing the skin homing
      receptors CLA and CCR4.

PMID- 16804322
TI  - A neuroactive steroid inhibits guinea pig airway sensory nerves via Maxi-K
      channel activation.
AB  - BACKGROUND: Although neurogenic inflammation via the activation of C-fibers in
      the airway may have an important role in the pathogenesis of asthma, their
      regulatory mechanism remains uncertain. OBJECTIVE: The pharmacological profiles
      of a neuroactive steroid, allotetrahydrocorticosterone, on the activation of C
      fibers in airway tissues were investigated, and the mechanism how a neuroactive
      steroid regulates airway inflammatory reactions was clarified. METHODS: The
      effects of allotetrahydrocorticosterone on electrical field stimulation-induced
      bronchial smooth muscle contraction in guinea pig airway tissues were
      investigated. The influences of K+ channel blockers and intracellular protein
      inhibitors on the effects of allotetrahydrocorticosterone were examined. RESULTS:
      Allotetrahydrocorticosterone dose-dependently inhibited electrical field
      stimulation-induced guinea pig bronchial smooth muscle contraction. The
      inhibitory effects of allotetrahydrocorticosterone on electrical field
      stimulation-induced bronchial contraction were reduced by the pretreatment of
      Maxi-K+ channel blockers, iberiotoxin and charybdotoxin, but not other K+ channel
      blockers, dendrotoxin or glibenclamide. Pretreatment with pertussis toxin
      diminished the inhibitory effect of allotetrahydrocorticosterone, but not an
      adenylate cyclase inhibitor, SQ 22536, nor a specific inhibitor of mitogen
      activated protein kinase kinase, PD 98059. CONCLUSIONS: These findings suggest
      that allotetrahydrocorticosterone negatively modulates the activation of C-fibers
      in guinea pig airway tissues via the opening of Maxi-K+ channels and a pertussis
      toxin-sensitive G-protein-coupled mechanism.

PMID- 16804323
TI  - Changes in the allergenicity during different preparations of Pomfret, Hilsa,
      Bhetki and mackerel fish as illustrated by enzyme-linked immunosorbent assay and
      immunoblotting.
AB  - BACKGROUND: Although the identification and characterization of several fish
      allergens have already been reported, there is almost no data on Indian fish
      allergens and the effect of thermal processing on their allergenicity. This study
      aimed at the evaluation of the changes in the level of allergenicity of 4 highly
      consumed Indian fishes, i.e. pomfret, hilsa, bhetki and mackerel, that occurred
      after boiling and frying. METHODS: In this study 110 patients with fish
      hypersensitivity as evidenced by clinical history and symptoms were recruited
      based on their positive skin prick test results. The raw, boiled and fried muscle
      extracts of the 4 fishes were prepared, and each extract was tested by ELISA and
      immunoblotting with patients' sera. RESULTS: ELISA and immunoblotting studies
      demonstrated that the raw muscle extracts of pomfret, hilsa, bhetki and mackerel
      were allergenic. While the allergenicity of boiled and fried extracts of pomfret
      and hilsa was considerably reduced, maximum allergenicity of bhetki was
      demonstrated in the fried extract. The degree of allergenicity of bhetki was
      demonstrated in the order fried>boiled>raw while that of mackerel followed the
      order raw>boiled approximately fried. CONCLUSION: The specific IgE-binding
      activity and immunoblot profile clearly showed that pomfret and hilsa fish
      allergens are heat-labile, while allergens of bhetki and mackerel maintained
      strong reactivity even after thermal treatment.

PMID- 16804324
TI  - Variant in promoter region of platelet-derived growth factor receptor-alpha
      (PDGFRalpha) gene is associated with the severity and allergic status of
      childhood asthma.
AB  - BACKGROUND: Upregulation of the platelet-derived growth factor receptor-alpha
      (PDGFRalpha) in airway myofibroblast cells is one of the mechanisms of airway
      remodeling. The genetic association between PDGFRalpha promoter polymorphism and
      severity of childhood asthma was examined. METHODS: Five single nucleotide
      polymorphisms (SNPs) at the promoter regions of the PDGFRalpha gene were
      genotyped in 277 unrelated allergic and nonallergic asthmatic children and 93 age
      matched controls. Promoter haplotypes were constructed using SNP genotyping data.
      The serum level of PDGF-AA, the ligand for PDGFRalpha, was assayed by ELISA kits.
      RESULTS: The genotype distribution of SNP rs1800810 (-1171G/C) in nonallergic
      asthma was significantly different from controls (p=0.038), as well as its allele
      distribution (p=0.028). Using haplotype analysis, the combination frequency of
      the low expression of H1 homozygous and heterozygous genotype (H1/H1+H1/H2) was
      significantly higher in nonallergic asthma as compared to controls (OR=1.94,
      CI=1.11-3.39, p<0.02). The frequency of H2/H2 homozygous was higher in persistent
      asthma than in intermittent asthma (p=0.008, OR=2.625). In addition, the PDGF-AA
      serum level in H2/H2 homozygous haplotype was significantly lower as compared to
      non-H2/H2 homozygous haplotype both in asthmatic (138.1+/-62.9 vs. 249.7+/-97.1
      ng/ml, p<0.05) and nonallergic asthmatic children (113.8+/-38.0 vs. 256.6+/-58.3
      ng/ml, p<0.05). CONCLUSIONS: The developmental deficiency due to the low
      expression of PDGFRalpha may be one of the susceptible factors for nonallergic
      asthmatic children. There was also an autocrine effect of lower PDGF-AA and
      higher PDGFRalpha expression that might lead to airway remodeling causing the
      severity of asthma.

PMID- 16804325
TI  - Unsuspected lupin allergens hidden in food.
AB  - BACKGROUND: Lupin is a herbaceous plant from the legume family whose seed
      allergens usually have cross-reaction with peanut. Lupin flour is used in human
      nutrition because of its high nutritional and functional qualities. AIMS: The aim
      of this work was to detect non-specified lupin proteins contained in several
      manufactured foods. METHODS: Serum from a patient suffering anaphylactic episodes
      after ingestion of a certain brand of cookies and with oral allergy syndrome
      after eating chicken bouillon was used as a tracer. Lupin seeds and commercial
      food extracts were analyzed by SDS-PAGE, immunoblotting and immunoblotting
      inhibition. Lupin extract allergenicity after thermal processing was also
      analyzed. RESULTS: A lupin allergen with a molecular weight close to 14 kDa was
      detected in extracts from cookies, a chicken bouillon cube and a chicken
      dehydrated soup. CONCLUSIONS: The presence of unsuspected, hidden non-specified
      lupin sources in food labeling was demonstrated. According to the results of this
      study, it is important for food-allergic patients that food labels should declare
      all the components irrespective of their quantity.

PMID- 16804326
TI  - Sensitization due to gum arabic (Acacia senegal): the cause of occupational
      allergic asthma or crossreaction to carbohydrates?
AB  - BACKGROUND: A pharmaceutical industry worker was exposed to dust of gum arabic in
      the tablet coating plant and complained of work-related shortness of breath,
      chest tightness, runny nose, itching and redness of the eyes. This case was
      investigated for allergy to gum arabic and compared with a control group. The aim
      of the study was to identify the IgE-binding components responsible for the work
      related symptoms. METHODS: Skin prick tests (SPTs)and specific IgE (sIgE)
      measurements with environmental and occupational allergens, spirometry and a
      specific bronchial challenge with gum arabic were performed. One hundred and
      nineteen control subjects underwent SPT with gum arabic and 43 controls were
      tested for sIgE. Crossreactivity between gum arabic and horse radish peroxidase
      was investigated by IgE CAP inhibition. A combined procedure of immunoblotting
      and periodate treatment was applied to identify the epitope nature of gum arabic.
      RESULTS: Allergy to gum arabic was shown by SPT, presence of sIgE and a positive
      bronchial challenge with gum arabic. Sensitization to gum arabic was demonstrated
      by SPT or sIgE in 7 and 5 controls, respectively. The results of inhibition with
      horse radish peroxidase, immunoblotting and periodate treatment suggest that gum
      arabic sIgE of the patient and 1 SPT-positive control subject were directed to
      the polypeptide chains of gum arabic. In contrast, gum arabic sIgE of the other
      controls reacted to carbohydrate components. CONCLUSIONS: Sensitization to gum
      arabic carbohydrate structures occurs casually in atopic patients with pollen
      sensitization without obvious exposure to gum arabic. This study suggests that
      allergy to gum arabic is mediated preferentially by IgE antibodies directed to
      polypeptide chains of gum arabic.

PMID- 16804327
TI  - Allergenic extracts for specific immunotherapy: to mix or not to mix?
AB  - Immunotherapy for allergic diseases give rise to questions about when a decision
      must be taken to define the number of extracts to be used in a single treatment.
      This represents a long-lasting matter of debate between American and European
      allergists, which seems to be without real solution. Through the use of extract
      based versus molecule-based diagnostic approaches we suggest a possible solution
      to this controversial issue. We used four model patients previously tested with
      allergenic extracts and later on selected on the basis of a panel of available
      allergenic molecules. Their reactivity patterns in term of extracts and molecules
      were compared and the decision for allergenic extract immunotherapy was made
      choosing either the 'classical' approach or the molecular approach. From our
      study it seems that molecules could offer the solution to the 'mixing' issue of
      allergenic extracts. This innovative approach seems to provide a solution for
      both the American and the European approach.

PMID- 16804328
TI  - Interleukin-10-treated dendritic cells do not inhibit Th2 immune responses in
      ovalbumin/alum-sensitized mice.
AB  - BACKGROUND: It is well known that the immunoregulatory cytokine interleukin (IL)
      10 inhibits the accessory function of human dendritic cells (DC) in vitro.
      Recently, we have shown that these IL-10 DC inhibit the production of T helper
      cell 1 (Th1) and T helper cell 2 (Th2) cytokines by T cells from atopic
      individuals in vitro. The current study was set out to analyze whether IL-10 DC
      also exert inhibitory effects in vivo in a murine model of allergy to ovalbumin
      adsorbed to the adjuvant aluminium hydroxide (OVA/alum). METHODS: OVA-pulsed or
      unpulsed bone marrow-derived DC, treated with IL-10 or left untreated during
      generation, were injected intravenously into BALB/c mice prior to and during
      OVA/alum sensitization, and sera and immune responses of mesenterial lymph node
      cells were analyzed. Additionally, bronchoalveolar lavage was performed after
      intranasal challenge with OVA. RESULTS: Treatment of BALB/c mice with OVA-pulsed
      DC led to a significantly enhanced proliferation as well as Th2 (IL-4, IL-5), Th1
      (interferon-gamma) and IL-10 cytokine production after restimulation of lymph
      node cells with OVA in vitro compared with OVA immunization alone. In contrast,
      using OVA-pulsed IL-10 DC for transfer, proliferation and cytokine production by
      lymph node cells were not enhanced. OVA-specific immunoglobulin G1 (IgG1) and
      IgG2a production were significantly increased after transfer of OVA-pulsed DC and
      OVA-pulsed IL-10 DC, respectively, whereas anti-OVA IgE production and airway
      eosinophilia remained unchanged. CONCLUSIONS: Our data indicate that IL-10
      treatment of DC decreases the Th1 and Th2 stimulatory capacity of DC but does not
      actually inhibit systemic (IgE) and local (airway inflammation) allergen-specific
      immune responses in a murine model of allergy.

PMID- 16804329
TI  - Regulation of anaphylactic IgG1 antibody production by IL-4 and IL-10.
AB  - BACKGROUND: Different cytokines have been implicated in the regulation of isotype
      expression in primary and secondary antibody responses. The aim of this study was
      to assess the regulation of anaphylactic IgG1 and IgE antibodies by IL-4, IL-10
      and IFN-gamma at different time points of the antibody response against PI, an
      immunosuppressive fraction of Ascaris suum extract, and ovalbumin (OVA). METHODS:
      Wild-type or cytokine-deficient C57BL/6 or BALB/c mice were immunized with PI or
      OVA in different adjuvants. Twenty days later, they were boosted with the
      respective antigen. IgG1 and IgE antibodies produced during primary and secondary
      responses were measured by passive cutaneous anaphylaxis. RESULTS: PI induced low
      levels of anaphylactic IgG1 antibodies in the primary response and moderate
      levels after the antigenic booster, which were IL-4-dependent. In the absence of
      IL-10 and IFN-gamma, PI-specific IgG1 and IgE enhanced significantly, indicating
      that these cytokines downregulated antibody production in primary and secondary
      responses. The IgG1 response to OVA in aluminium hydroxide or complete Freund's
      adjuvant was IL-4-dependent in the beginning of the primary response. Later on,
      it became only partially regulated by IL-4 in C57BL/6 mice and IL-4-independent
      in Th2-prone BALB/c mice. In contrast, IgE antibodies depended exclusively upon
      IL-4 during the entire time course. CONCLUSIONS: These results indicate, first,
      that the IL-4 dependency of anaphylactic IgG1 antibody production, mainly in the
      secondary response, varies among mouse strains, and, second, that the nature of
      the antigen determines whether IL-10 and IFN-gamma limit the potential to make
      large amounts of anaphylactic IgG1 and IgE.

PMID- 16804330
TI  - Expression of IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist in
      human aortic smooth muscle cells: effects of all-trans-retinoic acid.
AB  - The proinflammatory cytokine interleukin (IL)-1beta and the IL-1 receptor
      antagonist are expressed by atherosclerotic plaques and may be linked to the
      development of atherosclerosis. Existing evidence shows that retinoids and their
      receptors are involved in inflammatory response and that they are found in
      atherosclerotic plaques. In all-trans-retinoic acid (atRA)-treated human aortic
      smooth muscle cells (AOSMC), significant increases in IL-1beta levels were
      observed, compared with untreated cells. Examination of IL-1 receptor antagonist
      and IL-1 receptor type I levels did not show any difference between atRA-treated
      and -untreated AOSMC. The results show that atRA-treated AOSMC express both the
      precursor (33 kDa) and the active form (17 kDa) of the IL-1beta protein. atRA
      treated carotid lesions showed significantly elevated IL-1beta mRNA levels (2.9
      +/- 2.33) compared with untreated lesions (2.0 +/- 1.77; p < 0.05). These results
      support the role of atRA as a regulator of inflammation such as in
      atherosclerosis.

PMID- 16804331
TI  - Limited impact of the summer heat wave in France (2003) on hospital admissions
      and relapses for multiple sclerosis.
AB  - Patients with multiple sclerosis (MS) often report worsening of symptoms with
      increased environmental temperature. The aim of this paper was to determine
      whether or not the heat wave of the summer of 2003 in France was responsible for
      an increase in hospital admissions and relapses in MS patients. MS patients who
      were hospitalized between January 1,2000 and December 31,2003 were identified,
      and we established which patients were suffering relapses. Hospitalization and
      relapse seasonality were examined and analyzed according to ambient temperature
      variations. We did not observe a greater number of hospital admissions and
      relapses during the summer of 2003 compared to the previous 3 years. Results
      showed that MS hospitalizations display a significant trough in the winter
      season, especially in December, but no significant peak season or month was
      observed. There was no statistically significant correlation between mean ambient
      temperature and the number of admissions and relapses. The adverse symptoms
      associated with high temperatures that are usually observed in MS patients may
      require rapid rises in ambient temperate or in internal body temperature.

PMID- 16804332
TI  - Cognitive impairment and carotid atherosclerosis in a general Italian midlife and
      old population.
AB  - The authors describe the design and the general, ultrasonographic,
      neuropsychological methodology of an observational epidemiological population
      survey, named REMEMBER (Registry Evaluation Memory in Buttrio e Remanzacco)
      conducted in the northeast of Italy in a randomized stratified sample of 1,026
      subjects (554 F and 472 M) aged 55-98 years. The study was planned as cross
      sectional and longitudinal survey of cognitive impairment, cardiovascular risk
      factors, carotid atherosclerosis in a midlife and older Italian population
      sample. The objectives of the first phase are to assess the prevalence of the
      different types of dementia, the cognitive impairment non-dementia, the
      cardiovascular risk factors, the carotid intima-media thickness and arterial
      distensibility, and of depression. The conclusions of this study will make it
      possible to organize preventive and interventional strategies for these epidemic
      conditions.

PMID- 16804333
TI  - Prevalence of multiple sclerosis in Isfahan, Iran.
AB  - BACKGROUND: The prevalence of multiple sclerosis (MS) shows considerable
      variability all over the world. According to Kurtzke, Iran is considered to have
      a low prevalence. OBJECTIVE: To estimate the period prevalence and risk factors
      of MS in Isfahan, central part of Iran. METHODS: A cross-sectional case register
      study conducted between 2004 and 2005. In the province of Isfahan, Iran, all
      patients known to have definite MS during 2004 and 2005, being alive and resident
      within Isfahan as well as being a member of the Isfahan MS Association were
      included in the study. Demographic and case-related information was recorded.
      1,391 definite MS patients (308 men and 1,083 women) from the Isfahan MS
      Association, Iran, have been identified. The disease was confirmed using clinical
      information and MRI findings by a neurologist and radiologist. The patients were
      evaluated by interview and a questionnaire. Population data were obtained from
      the year 1999 Iran Census. The mean (SD) age of the participants was 32.5 (9.3)
      years with a mean (SD) duration of the disease of 6.4 (5.1) years for men and 6.9
      (5.3) years for women. RESULTS: The period prevalence of MS was 35.5 per 100,000
      [95% confidence interval (CI) 33.6-37.3] in a population of 3,923,255, with a
      higher rate in women than men [54.5 (95% CI: 51.1-57.8) for women and 14.9 (95%
      CI: 13.3-16.6) for men]. The female/male ratio was 3.6 (95% CI: 3.2-4.1). The
      direct age-adjusted period prevalence was 59.5 per 100,000 (95% CI: 44.8-75.2)
      for women and 17.0 per 100,000 (95% CI: 8.9-25.1) for men. MS rates were highest
      among 30- to 39-year-olds and decreased with increasing age. Sensory and visual
      disturbances were the most common initial presentations with a prevalence of
      51.1% (95% CI: 48.4-53.7) and 47.0% (95% CI: 44.4-49.7), respectively.
      CONCLUSION: Isfahan could be considered as an area with a medium to high risk of
      MS. This is in sharp contrast with the gradient hypothesis.

PMID- 16804337
TI  - [Clinical significance and natural history of "HBeAg negativity" in patients with
      chronic HBV infection].

PMID- 16804334
TI  - Growth hormone expression and secretion in pig pituitary and median eminence
      slices are not influenced by the VGF protein.
AB  - Body homeostasis is maintained by a complex system that involves the brain and
      the periphery via many circulating hormones. In recent years the VGF protein has
      been indicated as an important peptide affecting the regulation of body
      composition. We examined the effects of VGF on growth hormone (GH) expression and
      secretion in porcine pituitary slices, incubated alone (group 1) or with stalk
      median eminence (SME) (group 2). After 2 h (time 0), medium was removed and
      replaced with a fresh one; tissues were challenged with VGF (10(-6) M, 10(-8) M)
      alone or with ghrelin (10(-8) M) or growth hormone-releasing hormone (GHRH) (10(
      8) M). Medium was replaced again 2 h (+2) and 6 h (+6) later. None of the VGF
      concentrations influenced GH secretion in either group; the association with GHRH
      or ghrelin appeared ineffective in influencing GH secretion as compared with the
      effects of GH mRNA expression and was not influenced by VGF treatments. The
      presence of SME had an additive effect on GH expression. Collectively, our
      results confirm previous findings on GH regulation; however, further
      investigations are needed to establish whether the modulation of GH secretion in
      the absence of nutrients involves the balance of GHRH/ghrelin receptors at
      pituitary levels. As for VGF, a crucial aspect to clarify is whether its lack of
      effects depends on our experimental conditions or, alternatively, it is not
      effective at all.

PMID- 16804338
TI  - [Prevalence and clinical implications of occult hepatitis B virus infection].

PMID- 16804339
TI  - [Immunology of hepatitis C: clinical significance of T cell response].
AB  - Hepatitis C virus (HCV) infection is a worldwide problem in terms of public
      health. It causes chronic hepatitis C in 60-80% of patients after acute hepatitis
      C. Chronic hepatitis C can progress to liver cirrhosis and hepatocellular
      carcinoma. In the present time, combination therapy of pegylated interferon-alpha
      and ribavirin is the standard therapy for hepatitis C, but it results in
      sustained virologic response only in 45-80% of treated patients. In addition,
      there is no available effective vaccine for HCV. To develop effective
      immunotherapy or preventive vaccine, understanding of the immune response against
      HCV is prerequisite. Among several components of immune system, T cells play a
      key role in the clearance of HCV and immunopathology during hepatitis C. In the
      study of HCV infection, however, the most important limiting factor is the
      absence of small animal model as only humans and chimpanzees can be infected by
      HCV. In this review, T cell response against HCV, which has been known from the
      studies of the HCV-infected patients and chimpanzees, will be discussed in
      several circumstances, including acute hepatitis C, chronic hepatitis C and
      recovered status from hepatitis C.

PMID- 16804340
TI  - [Action mechanism in immunopathogenesis and clearance of HBV].
AB  - Hepatitis B virus (HBV) currently infects more than 400 million people worldwide
      and they are at risk of developing chronic liver disease, cirrhosis and
      hepatocellular carcinoma. The immune response to HBV-encoded antigens is
      responsible both for viral clearance and for disease pathogenesis during HBV
      infection. While the humoral antibody response to viral envelope antigens
      contributes to the clearance of circulating virus particles, the cellular immune
      responses to the envelope, nucleocapsid, and polymerase antigens were known to
      eliminate virus in infected hepatocytes through cytolytic as well as noncytolytic
      mechanisms. Liver injury could be initiated by an immune response against HBV,
      but mainly resulted from HBV non-specific lymphocytes and macrophages. There are
      growing evidences that T helper 1 memory T cells play a predominant role in
      suppressing viral replication mainly by IFN-gamma through noncytolytic antiviral
      mechanism. Elucidation of the immunological and virological basis for HBV
      infection may yield effective immunotherapeutic and antiviral strategies to
      terminate chronic HBV infection.

PMID- 16804341
TI  - [Natural history of HBeAg negative chronic hepatitis B virus infection: a cohort
      study].
AB  - BACKGROUND/AIMS: The long-term virologic and biochemical changes in patients with
      HBeAg negative HBV infection, especially in Asia, remain unclear. To address this
      issue, we conducted a 3 year- retrospective, cohort study. METHODS: A total of
      157 patients with HBeAg negative HBV infection who were monitored without
      treatment were reviewed between January 1999 and March 2004. Those patients were
      followed up every 3 months with liver function tests and serologic tests. All
      patients were stratified into 3 groups; inactive carrier (IC), viremic carrier
      (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization
      assay (sensitivity: 1.4 x 10(5)) genomes/mL, Digene Diagnostics, Silver Spring,
      USA). RESULTS: The median age of enrolled patients was 42.7 years (M:F=2.3:1). By
      single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH
      varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over
      time (P=0.002) and transition rates among three groups after 3 years of follow-up
      are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a
      disease state in the middle of transition from IC to CH. CONCLUSIONS: We
      demonstrated the dynamic changing patterns of HBeAg negative CH with time, of
      which the change from IC or VC to CH was dominant.

PMID- 16804342
TI  - [Correlation of HBV DNA level and viral breakthrough during lamivudine therapy
      for chronic hepatitis B].
AB  - BACKGROUND/AIMS: Lamivudine is an effective therapy in chronic hepatitis B
      patients, but the emergence of resistant hepatitis B virus (HBV) mutants is a
      major concern. This study was performed to investigate whether serum viral DNA
      levels during lamivudine therapy are related with viral breakthrough in patients
      with chronic HBV infection. METHODS: This study consisting of 103 patients was
      performed retrospectively and prospectively. Follow-up duration was 24 months
      after lamivudine therapy. Serum HBV DNA levels were quantified by PCR-based assay
      every 6 months. RESULTS: Cumulative rate of viral breakthrough was 0%, 19.4%,
      36%, and 48.5% in 6, 12, 18, and 24 months respectively. The rate of viral
      breakthrough in 24 months increased as serum HBV DNA levels increased at 6
      months. When serum HBV DNA levels were 2-3 log10, 3-4 log10, 4-5 log10, and 5
      log10 copies/mL or more, the breakthrough rates were significantly higher than
      that of the HBV DNA level less than 2 log10 copies/mL. The relative risks were
      1.10, 1.93, 2.69, 3.21 respectively (P<0.001). The viral breakthrough rate also
      increased as serum HBV DNA levels at 12 months increased. When the HBV DNA levels
      were 2-3 log10, 3-4 log10, 4-5 log10, and 5 log10 copies/ mL or more, the
      breakthrough rate were significantly higher than those of HBV DNA level less than
      2 log10 copies/mL. The relative risks were 2.42, 4.35, 3.73, 2.61, respectively
      (P=0.002). CONCLUSIONS: The serum HBV DNA levels at 6 months and 12 months during
      lamivudine therapy can be closely correlated with the rate of viral breakthrough
      in 24 months.

PMID- 16804343
TI  - [Comparison of clinical outcome between patients continuing and discontinuing
      lamivudine therapy in acute exacerbation after viral breakthrough during
      lamivudine therapy in chronic hepatitis B].
AB  - BACKGROUNDS/AIMS: Continuation of lamivudine therapy is controversial for
      patients with chronic hepatitis B when viral breakthrough occurs. Moreover, the
      effect of continuous lamivudine therapy is unknown in patients with acute
      exacerbation after viral breakthrough. We assessed clinical course of acute
      exacerbation after viral breakthrough in patients who continued and discontinued
      lamivudine therapy. METHODS: Medical records of 109 patients with viral
      breakthrough during lamivudine therapy were reviewed. Of 40 patients with acute
      exacerbation (ALT level > 5 x ULN), adefovir dipivoxil was unavailable in 38
      patients. These 38 patients (mean age 42.6 years; male/female, 34/6) were divided
      into continuation (n=21) and discontinuation (n=17) groups. Clinical courses of
      the 2 groups were compared. RESULTS: During follow-up period (mean, 27 months;
      range, 6-60 months), ALT levels decreased to < 2 x ULN in 11 patients (52%) of
      continuation group and 9 patients (53%) of discontinuation group, varied from 2 x
      to 5 x ULN in 9 (43%) and 5 (29%), respectively, and increased to > 5 x ULN in 1
      (5%) and 3 (18%), respectively, with no statistical significance (P=.417).
      CONCLUSIONS: When acute exacerbation of ALT levels occurs after viral
      breakthrough during lamivudine administration in patients with compensated
      chronic hepatitis B, continuation of lamivudine may have no advantage over
      discontinuation.

PMID- 16804344
TI  - Change of hepatitis B virus DNA status in anti-HBc positive liver graft.
AB  - BACKGROUND/AIMS: Many patients with positive anti-HBc, but negative HBsAg, are
      known to harbor occult HBV infection, which may transmit the virus through the
      graft in liver transplantation. We examined the change of HBV DNA within the
      liver allograft tissue of the donor with positive anti-HBc, but negative HBsAg,
      before and after the transplantation and assessed its significance. METHODS:
      Twenty-eight patients with available posttransplant biopsies that received anti
      HBc positive liver allografts between April 2000 and November 2003 were enrolled
      in the study. Intraoperative wedge biopsy of donor liver and needle biopsy of the
      recipient around the 12th postoperative day were used. HBV DNA within the liver
      tissue was identified by polymerase chain reaction technique using paraffin
      embedded liver tissue. RESULTS: Among 13 patients that showed positive
      amplification before transplantation, 10 turned negative and 3 remained positive
      after transplantation. One patient, who was negative, became positive after
      transplantation. Three patients had recurrent HBV infection, but none had
      positive PCR before or after transplantation and recurrence was not associated
      with PCR results. Donors with low anti-HBs titer were more likely to be PCR
      positive compared to donors with high anti-HBs serology (P<0.05). CONCLUSIONS:
      Under adequate prophylactic measures, the presence of HBV DNA within the liver
      tissue does not affect recurrence and most allografts harboring HBV DNA before
      transplantation will eventually show viral clearance. However, many anti-HBc
      positive allografts are infected by HBV at subclinical level so vigilant
      surveillance is essential.

PMID- 16804345
TI  - [Detection of Intrahepatic HBV DNA in HBsAg-negative liver diseases].
AB  - BACKGROUNDS/AIMS: Occult HBV infection is characterized by the presence of HBV
      infection with undetectable HBsAg. This study was carried out to find out the
      frequency of HBV infection in HBsAg- negative patients. METHODS: Fifty-six HBsAg
      negative patients including 17 anti-HCV positive patients were evaluated.
      Patients were grouped according to their serological status; group A (anti-HBc+,
      anti-HBs-, n=16), B (anti-HBc+, anti-HBs+, n=26), and C (anti-HBc-, anti-HBs+/-,
      n=14). DNA was extracted from frozen liver biopsy specimen, and HBV DNA level was
      measured with real-time PCR. RESULTS: Overall frequency of detectable
      intrahepatic HBV DNA was 34% (19/56). The frequency was 56% (9/16) in group A,
      31% (8/26) in group B and 14% (2/14) in group C (P=0.01). Intrahepatic HBV DNA
      levels were as follows; 2,010 +/- 6,660 copies/mg in group A, 6,180 +/- 29,530
      copies/mg in group B and 350 +/- 1,220 copies/mg in group C. The frequency of
      occult HBV infection was not increased in anti-HCV positive patients.
      CONCLUSIONS: Intrahepatic HBV DNA is frequently detected in anti-HBc positive,
      HBsAg-negative patients, although the concentration is low.

PMID- 16804346
TI  - [Modified CLIP score as a new prognostic index for patients with hepatocellular
      carcinoma].
AB  - BACKGROUNDS/AIMS: The prognosis of cirrhotic patients with hepatocellular
      carcinoma (HCC) depends on both residual liver function and tumor
      characteristics. The aims of this study was to construct a new prognostic index
      for HCC patients: the modified CLIP score, and to compare its discriminatory
      ability and predictive power with those of the CLIP score that is currently the
      most commonly used integrated staging score in patients of HCC. METHODS: A
      retrospective analysis of 237 cases of HCC diagnosed at Dong-A university
      hospital was performed. Prognostic analysis was performed for single variables by
      estimating survival distributions with the Kaplan-Meier's method, and
      statistically compared by the log-rank test. RESULTS: Patients had a mean age of
      57.5 years and were predominantly males (79.7%). The overall median survival
      period was 25.7 months. It was correlated to ascites, portal vein thrombosis,
      AFP, tumor size, and Child-Pugh classification. The median survival period was
      41.0, 25.2, 13.8, 13.4, and 6.5 months for CLIP scores 0, 1, 2, 3, and 4 to 6,
      respectively (P<0.001), and 42.1, 34.0, 25.7, 14.0, and 6.8 months for modified
      CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001). The Kaplan-Meier's
      curve showed that the modified CLIP score had additional explanatory power above
      that of the CLIP score. CONCLUSIONS: The modified CLIP score, compared with the
      CLIP score, particularly in the score 2- to 3- patient groups of HCC, had greater
      discriminant ability and survival predictive power, but was not able to
      discriminate 4- to 6- patient group.

PMID- 16804348
TI  - [Nine cases of sporadic acute hepatitis E in Korea].
AB  - Hepatitis E virus is an enterically transmitted virus that causes endemic cases
      of acute hepatitis in many countries in Africa, and Southeast and Central Asia.
      Sporadic cases of acute hepatitis E also have been reported in developed
      countries. In non-endemic areas, most of the sporadic cases of hepatitis E are
      introduced from the endemic areas. Until now, only three cases of acute hepatitis
      E have been reported in Korea. Recently, we experienced nine cases of acute
      hepatitis, in which serologic studies showed positive of IgM anti-HEV. We report
      these as cases of acute hepatitis E. These cases suggest that HEV infection
      occurs sporadically in Korea and should be considered as a cause of cryptogenic
      acute hepatitis.

PMID- 16804347
TI  - [The relationship between serum adiponectin level and serum alanine
      aminotransferase elevation in Korean male with nonalcoholic fatty liver disease].
AB  - BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) comprises a large part
      of chronic liver diseases. Recently it was reported that adipokines are closely
      associated with the common risk factors for NAFLD, such as obesity, diabetes,
      dyslipidemia, and insulin resistance. We aimed to evaluate the changes in serum
      adiponectin, resistin and leptin concentrations related to alanine
      aminotransferase (ALT) elevations in Korean men with NAFLD. METHODS: We studies
      38 men who were diagnosed with fatty liver by abdominal ultrasonography. None had
      a history of excessive alcohol consumption, autoimmune hepatitis, inherited or
      metabolic liver disease or viral hepatitis. The subjects were divided into two
      groups. One group had normal levels of ALT (n=28) and the other had increased ALT
      (n=10). We compared anthropometrical parameters, biochemical items and serum
      adipokine levels between these two groups. RESULTS: Serum adiponectin levels were
      lower in the increased ALT group than in the normal ALT group (3.89 +/- 1.77 vs
      7.01 +/- 2.54 microgram/dL, P=0.001). But there were no significant differences
      in serum leptin and resistin levels between two groups (4.02 +/- 2.04 vs 3.26 +/-
      1.41 ng/mL, p=0.245, 80.14 +/- 14.8 vs 80.5 +/- 11.34 ng/mL, P=0.937,
      respectively). Multiple linear regression analyses demonstrated that the serum
      adiponectin level is inversely correlated with serum ALT level and that the serum
      aspartate aminotransferase (AST) level is positively correlated with the serum
      ALT level. CONCLUSIONS: Our study shows that hypoadiponectinemia is associated
      with an ALT elevation in patients with NAFLD. Adiponectin may play an indirect
      role in the development of NAFLD.

PMID- 16804350
TI  - [Alcoholic hepatitis].

PMID- 16804349
TI  - [A case of cholestatic hepatitis induced by epstein-barr virus infection].
AB  - Acute viral hepatitis in human can be caused by a large number of viruses with a
      wide range of clinical manifestations and laboratory findings. EBV is a rare
      causative agent of an acute hepatitis, during the course of infectious
      mononucleosis. Hepatic manifestations of EBV are usually mild and resolve without
      serious complications. EBV is rather uncommonly confirmed as an etiologic agent
      in acute viral hepatitis of adults and it rarely causes cholestatic hepatitis. We
      report a case of EBV hepatitis with cholestatic feature that was verified through
      serum viral marker and liver biopsy.

PMID- 16804351
TI  - [Double-contrast MR Imaging for Hepatocellular Carcinoma].

PMID- 16804352
TI  - [Evaluation of the hepatocellular carcinoma staging systems].

PMID- 16804362
TI  - Impact of moderate physical exercise--in comparison with dietary restrictions--on
      age-associated decline in cell-mediated immunity of Sprague-Dawley rats.
AB  - BACKGROUND AND AIMS: Moderate physical exercise and dietary restriction have both
      been demonstrated to delay some of the adverse effects of aging. In order to
      elucidate similarities or dissimilarities in their mode of action on the aging
      immune system in a comparative setting, we examined significant parameters of
      cell-mediated immunity in Sprague- Dawley rats. METHODS: Male Sprague-Dawley
      rats, housed individually, were divided into four groups, living from 5 months
      (baseline group BL) up to 15, 19 and 23 months of age as follows: voluntary
      running in wheels (RW), food restricted by feeding to pair weight with RW animals
      (PW), forced running on treadmills (TM), and sedentary controls with ad libitum
      access to food (S1). White blood cell counts, capacity for lymphocyte
      proliferation in response to Concanavalin A, and interleukin-2 (IL-2) plasma
      concentrations were determined. RESULTS: White blood cell counts and the cell
      numbers of lymphocytes, neutrophil and eosinophil granulocytes were significantly
      lower in the older RW and PW groups. We observed influences of forced exercise on
      lymphocyte proliferation: blastogenic reactivity was higher in TM animals
      compared with RW and PW animals at 23 months of age. Exclusively for RW animals,
      we found lower plasma concentrations of IL-2 at 23 months. CONCLUSIONS: Our data
      support the idea that moderate physical exercise modulates age-associated decline
      in the cell-mediated immunity of old Sprague-Dawley rats significantly more than
      corresponding dietary restrictions.

PMID- 16804363
TI  - Leg ulcers in elderly on hydroxyurea: a single center experience in Ph-
      myeloproliferative disorders and review of literature.
AB  - Hydroxyurea (HU) is effective in controlling thrombocytosis while reducing the
      risk of thrombosis in essential thrombocythemia (ET), polycythemia vera (PV) and
      myelofibrosis (MF). However, HU may carry more or less severe side-effects. Rare
      cases of patients with painful leg ulcers have been published. We report our
      experience on such a side-effect in a large cohort of patients with ET and PV
      treated with HU and review the literature on the topic. Five (4%) out of our 124
      patients (69 ET, 51 PV, 4 MF; 49 males, 75 females; mean age at diagnosis 59.1+/
      11.8 years) treated with HU developed painful leg ulcers. Sixty-one other
      patients affected with Phmyeloproliferative disorders (Ph- MPD) developing HU
      related painful leg ulcers are described in the English literature. All our five
      patients were women and developed leg ulcers over the age of 75. Sixty-five
      percent of all described cases are women; 59% were over 65 years of age and 45%
      over 70. Most cases received over 1 gr HU per day for at least 1 year. The
      pathogenesis of HU-induced skin ulcers remains elusive. Treatment is difficult
      and requires prompt cessation of HU therapy.

PMID- 16804364
TI  - Clinical advantages of laparoscopic colorectal cancer surgery in the elderly.
AB  - BACKGROUND AND AIMS: Elderly patients have a high incidence of colorectal cancer,
      which may be associated with increased morbidity and mortality due to complex
      comorbidity and diminished cardiopulmonary reserves. The aims of this study were
      to compare the outcomes of laparoscopic colorectal cancer surgery with those
      observed in traditional open surgery in patients aged over 70 years. METHODS:
      Between January 2003 and October 2004, 51 patients aged over 70 years with
      colorectal cancer, who underwent laparoscopic surgery (LAP group), were evaluated
      and compared with 102 controls (also over 70 years old) treated by traditional
      open surgery (OPEN group) in the same period. All patients were evaluated with
      respect to the American Society of Anesthesiologists (ASA) classification,
      surgery-related complications, and postoperative recovery. RESULTS: No surgery
      related death was observed in the LAP group, whereas two deaths occurred in the
      OPEN group for severe post-operative pulmonary infection and anastomotic leak,
      respectively. No pneumoperitoneum-related complications were observed in the LAP
      group; 2 (3.9%) patients required conversion to open surgery, because of the
      unexpectedly bulky tumor and severe adhesions in the abdominal cavity. With the
      increase in patients' age, increased ASA classification was observed. No
      significant differences were observed in gender, Dukes' staging or types of
      procedures between LAP and OPEN groups. The overall morbidity in the LAP group
      was significantly less than that of the OPEN group [17.6% (9/51) vs 37.3%
      (38/102), p=0.013]. Mean blood loss, time to flatus passage, and time to semi
      liquid diet in the LAP group were significantly shorter than those of the OPEN
      group (90.7+/-49.9 vs 150.3+/-108.7 ml, 2.4+/-1.2 vs 3.5+/-2.9 d, 5.0+/-1.8 vs
      5.9+/-1.2 d, respectively, p<0.05). No significant differences were observed in
      terms of mean operation time or hospital stay between LAP and OPEN groups.
      CONCLUSION: Laparoscopic colorectal cancer surgery in elderly patients with colon
      cancer has clinically significant advantages over traditional open surgery, and
      appears to be the ideal surgical choice for the elderly.

PMID- 16804365
TI  - Weight change and mortality among older Mexican Americans.
AB  - BACKGROUND AND AIMS: Weight changes are predictors of health outcomes in older
      people. The purpose of this study is to examine the association between 2-year
      weight change and mortality in older Mexican Americans. METHODS: Seven year
      prospective cohort study of 1,749 non-institutionalized Mexican American men and
      women aged 65 and older residing in five Southwestern states. Measures include
      self-reports of medical conditions (heart attack, stroke, diabetes, hypertension,
      hip fracture or cancer), functional disability, high depressive symptoms, smoking
      status, a summary performance score of lower body function, hand grip muscle
      strength, and body mass index (BMI). Weight change was examined by comparing the
      baseline weight to the weight two years later to estimate the hazard of death
      within the following five-year period. RESULTS: Of the 1,749 subjects, 396
      (22.6%) lost 5% or more weight, 984 (56.3%) had weight that remained stable, and
      369 (21.1%) gained 5% or more weight between baseline and the 2-year follow-up
      period. Of the ones who lost 5% of weight, 28% died as compared to 19.7% and
      15.2% of those whose weight remained stable and those who gained weight after 5
      years, respectively. The hazard ratio (HR) of death for the group that lost 5% or
      more of their weight compared to the reference group (stable weight) was 1.35
      (95% CI 1.06-1.70) after controlling for demographic variables, BMI, and waist
      circumference at baseline and 1.32 (95% CI 1.04-1.67) after controlling for all
      covariates. The HR of death for the group that gained 5% or more of weight was
      0.78 (95% CI 0.58-1.05) after controlling for demographic variables, BMI, and
      waist circumference at baseline and 0.77 (95% CI 0.57-1.04) after controlling for
      all covariates. CONCLUSIONS: Weight loss is an independent predictor of mortality
      among older Mexican Americans, after controlling for relevant risk factors.

PMID- 16804366
TI  - Body mass index as a predictor of mortality in community-dwelling seniors.
AB  - BACKGROUND AND AIMS: The relationship between body mass index (BMI) and mortality
      remains inconclusive in seniors. This study aimed at assessing this relationship
      in a community-dwelling elderly population in Japan. METHODS: The subjects were
      371 Japanese elders, 65 years old and older, who lived in a geographically well
      defined rural community and had participated in a general health screening
      program in 1995. Both height and weight of subjects were measured directly by
      medical staff. Subjects were classified into three groups according to their BMI
      values: low, <18.5; normal, 18.5-25.0; and high, >25.0. Univariate analysis was
      applied to explore potential associations between mortality and possible
      confounders. Multivariate Cox proportional hazards models were used to analyze
      the association between mortality and BMI, after adjusting for other risk
      factors. RESULTS: At baseline, 54 subjects (14.6%) had BMI values in the low
      range, 280 (75.5%) in the normal range, and 37 (10.0%) in the high range. All 371
      subjects were followed prospectively for mortality. Over the next five years, 37
      subjects had died. In univariate analysis, male sex, age, BMI and serum
      creatinine were associated with mortality. The mortality rate in the low BMI
      group was about twice that in the normal BMI group. No deaths were observed in
      the higher BMI group. In multivariate analysis, age and low BMI were associated
      with mortality. CONCLUSIONS: BMI may be a useful predictor of mortality among
      seniors living in the general, non-institutionalized population.

PMID- 16804367
TI  - Comparative vs global self-rated health: associations with age and functional
      ability.
AB  - BACKGROUND AND AIMS: This study examined the relationship of age and functional
      ability with comparative (age-referential) and global self-rated health (SRH),
      and the possible effect of selection bias. The focus is on differences between
      these questions and on the consequences which these differences have in research.
      METHODS: The data came from the second wave of the Tampere Longitudinal Study on
      Ageing (TamELSA), consisting of 830 persons aged 60-99 years. The associations of
      both self-rated health measures with age and functional ability were examined
      using multinomial regression analyses. RESULTS: People with increasing age,
      particularly over 80-year-old, are inclined to rate their health better than that
      of their age peers. The association of older age with better comparative SRH
      became even stronger after adjustment for functional ability, chronic diseases
      and sociodemographic factors. The relation of older age with global SRH was
      weaker than that with age-referential SRH. By contrast, functional ability was
      more strongly associated with global than with comparative SRH. CONCLUSIONS: Our
      results suggest that comparative and global self-rated health cannot be used
      interchangeably. The comparative measure is more strongly "calibrated" by age.
      Therefore, when SRH is used as a measure in survey studies or in clinical
      settings, the global question should be preferred.

PMID- 16804368
TI  - Predictive value of health-related fitness tests for self-reported mobility
      difficulties among high-functioning elderly men and women.
AB  - BACKGROUND AND AIMS: The functional independence of elderly populations
      deteriorates with age. Several tests of physical performance have been developed
      for screening elderly persons who are at risk of losing their functional
      independence. The purpose of the present study was to investigate whether several
      components of health-related fitness (HRF) are valid in predicting the occurrence
      of self-reported mobility difficulties (MD) among high-functioning older adults.
      METHODS: Subjects were community-dwelling men and women, born 1917-1941, who
      participated in the assessment of HRF [6.1-m (20-ft) walk, one-leg stand,
      backwards walk, trunk side-bending, dynamic back extension, one-leg squat, 1-km
      walk] and who were free of MD in 1996 (no difficulties in walking 2- km, n=788;
      no difficulties in climbing stairs, n=647). Postal questionnaires were used to
      assess the prevalence of MD in 1996 and the occurrence of new MD in 2002.
      Logistic regression analysis was used as the statistical method. RESULTS: Both
      inability to perform the backwards walk and a poorer result in it were associated
      with risk of walking difficulties in the logistic model, with all the
      statistically significant single test items included. Results of 1-km walk time
      and one-leg squat strength test were also associated with risk, although the
      squat was statistically significant only in two older birth cohorts. Regarding
      stair-climbing difficulties, poorer results in the 1-km walk, dynamic back
      extension and one-leg squat tests were associated with increased risk of MD.
      CONCLUSIONS: The backwards walk, one-leg squat, dynamic back extension and 1-km
      walk tests were the best predictors of MD. These tests are recommended for use in
      screening high-functioning older people at risk of MD, as well as to target
      physical activity counseling to those components of HRF that are important for
      functional independence.

PMID- 16804369
TI  - Exercise intervention of 65+-year-old men and women: functional ability and
      health care costs.
AB  - BACKGROUND AND AIMS: Physical activity has been demonstrated to prevent physical
      impairment in elderly people. Physical impairment often leads to dependency and
      the need for help or health services. Therefore, participation in physical
      activity programs (PAP) may reduce health care costs. The aim of this study was
      to evaluate: i) the effect of a PAP on functional ability and the use of health
      care services; ii) the possible association between level of functional ability
      and public health care costs. METHODS: 185 participants aged 65+ (mean: 74.7 yrs)
      were recruited. The intervention consisted of a group-based multicomponent PAP,
      1.5 hours, once a week, for 5 months. Functional ability was assessed by
      questionnaire and physical performance tests before and after the PAP. Economic
      analyses were based on data collected retrospectively from public registers and
      questionnaires describing the use of health care services (e.g., public home
      care, GPs, hospitals). RESULTS: Participants revealed a high level of functional
      ability. Only a few significant differences between pre- and posttests were
      observed. Many participants incurred no or very low public health care costs. The
      probability of using health care services decreased with better functional
      ability scores and lower age. CONCLUSIONS: Participants in this study maintained
      their level of functional ability in the intervention period with unaltered use
      of health care resources.

PMID- 16804370
TI  - Evaluation of an osteoporosis and fall risk intervention program for community
      dwelling elderly. A quasi-experimental study of behavioral modifications.
AB  - BACKGROUND AND AIMS: Osteoporosis and fall fractures are increasing problems
      amongst the elderly. The aim of this study was to explore whether combined
      population-based and individual interventions directed at risk factors for
      osteoporosis and falls result in behavioral changes in an elderly population.
      METHODS: A quasi-experimental design was used for the study. Persons aged >or=65
      years were randomly selected in the intervention and control community. An
      intervention program was managed from the primary health care center and
      delivered to the community. Health education was designed to increase awareness
      of risk factors for the development of osteoporosis and falling. Questionnaires
      about lifestyle, health, previous fractures, safety behavior and physical
      activity level were distributed at baseline in 1989 and at the follow-ups in 1992
      and 1994 in both communities. RESULTS: There was a difference of 17.7% between
      the dual intervention (receiving both population-based and individual
      interventions) and the control samples regarding the self-reported use of
      shoe/cane spikes, and a difference of 20.5% regarding the reported "moderate
      level" of physical activity in 1994. There was an increase in the number of
      participants in the dual intervention sample who, at baseline, had not reported
      equipping their homes with non-slip mats and removing loose rugs but who did
      report these changes in 1994. The increase in the reported use of shoe/cane
      spikes in the dual intervention sample was observed mainly for the period 1992
      1994. CONCLUSIONS: A public health intervention model, including both population
      based and individual interventions, can contribute to behavioral changes in the
      prevention of falls and changed physical activity patterns amongst elderly
      people.

PMID- 16804371
TI  - A novel exercise for improving lower-extremity functional fitness in the elderly.
AB  - BACKGROUND AND AIMS: Many falls in the elderly are caused by tripping. After
      tripping, a certain level of lower-extremity functional fitness is necessary, in
      order to make protective responses and to avoid falling. The purpose of this
      study was to test whether our new exercise program (a square-stepping exercise:
      SSE) would improve lower-extremity functional fitness in the elderly. METHODS:
      Fifty-two individuals aged 60-80 years were divided into two groups (non
      randomized control design); SSE (n=26) and controls (n=26). Lower-extremity
      functional fitness was defined as standing up from a lying position (agility),
      chair-stand in ten seconds (leg power), walking round two cones (locomotion
      speed), sit-and-reach (flexibility) and single-leg balance with eyes closed
      (balance). The SSE group participated in a six-month regimen of SSE once a week.
      SSE was performed on a thin mat of 250 cm by 100 cm, partitioned into 40 small
      squares (25 cm each side). SSE included not only forward steps but also backward,
      lateral and oblique steps, and step patterns were progressively made more
      complicated. Controls maintained their usual lifestyles. RESULTS: In the SSE
      group, significant improvements were observed in agility, leg power, locomotion
      speed, flexibility and balance. No significant changes were detected in any tests
      in the control group. CONCLUSIONS: The SSE program improved lower-extremity
      functional fitness, lack of which constitutes a risk factor for falls in the
      elderly. This program should be tested further to determine if it can effectively
      reduce the incidence of falls in the elderly.

PMID- 16804372
TI  - An assessment of inappropriate hospital bed utilization by elderly patients in
      southern Italy.
AB  - BACKGROUND AND AIMS: The aims of this study were to quantify the rate of
      inappropriate hospital admissions and days of stay among elderly patients, and to
      identify the main causes of such inappropriateness. METHODS: A random sample of
      560 medical records of patients aged 65 and over, admitted to medical and
      surgical wards of a non-teaching hospital in Catanzaro (Italy) were reviewed
      (occupation rate: 81.9%, average length of stay: 5.6 days; hospitalization rate
      in the area: 130.8 per 1,000 inhabitants). RESULTS: Of the 529 patient days
      reviewed, 9.8% of hospital admissions were judged to be inappropriate, and the
      level of inappropriate hospital days of stay was 39.5%. The inappropriateness of
      admission was significantly higher for younger patients and for those whose
      admission was programmed. Demographic and hospital variables were significant
      predictors of the risk of inappropriateness per day of care: women, those not
      living alone, patients admitted with a more severe burden of overall comorbidity,
      patients inappropriately admitted, and those sampled close to discharge were more
      likely to be classified as inappropriate. Inappropriate admission was due to
      premature admission, an overcautious physician's attitude in the management of a
      patient, and admission for a diagnostic or therapeutic procedure that should have
      been performed on an out-patient basis. The reasons for inappropriate hospital
      stay were: physician's lack of decision regarding discharge of a patient and
      delays in scheduling a diagnostic or therapeutic procedure. CONCLUSION:
      Interventions are needed in order to increase the quality and efficiency of
      hospital care, by rectifying the attitudes and behaviors of Italian physicians.

PMID- 16804373
TI  - Age-correlated decline in [3H]tiagabine binding to GAT-1 in human frontal cortex.
AB  - BACKGROUND AND AIMS: In spite of the fact that GABA is a significant transmitter,
      little is known about the GABA system in aging, compared with other transmitter
      systems. [(3)H]tiagabine is a ligand for GABAergic neurons, which binds with 10
      fold higher affinity to the GABA uptake site than [(3)H]nipecotic acid. The aim
      of this study was to study the binding of [(3)H]tiagabine to the GABA transporter
      1, GAT-1, in human frontal cortex and cingulate cortex from individuals of
      varying ages. METHODS: [(3)H]tiagabine binding experiments were conducted on post
      mortem brain tissue from 19 individuals (age range 17-78 years) without known
      neurological or psychiatric disorders. Binding data vs age and postmortem
      interval was analysed by Pearson correlation. RESULTS: The density of
      [(3)H]tiagabine binding to GAT- 1 decreased significantly with increasing age in
      the frontal cortex, whereas binding affinity was unchanged. No significant
      alterations in binding parameters were observed in the cingulate cortex. No
      correlation was found between post-mortem delay and the number of [(3)H]tiagabine
      binding sites. CONCLUSIONS: According to the present study, presynaptical
      alterations in the GABA system are correlated with aging in the frontal cortex of
      the human brain. Further studies involving a broader range of brain regions seem
      warranted, to confirm the present findings and to enlarge knowledge about the
      GABA system in aging.

PMID- 16804374
TI  - Robot-aided intensive training in post-stroke recovery.
AB  - The successful motor rehabilitation of stroke patients requires an intensive and
      task-specific therapy approach. The plasticity of the adult human brain provides
      opportunities to enhance traditional rehabilitation programs for these
      individuals. Intensive robot-aided sensorimotor training may have a positive
      effect on reducing impairment and disability and increasing reorganization of the
      adult brain. This approach may therefore efficaciously complement standard post
      stroke multidisciplinary programs as shown by recent experimental trials.

PMID- 16804377
TI  - Can we control the spread of antibiotic-resistant nosocomial pathogens? The
      methicillin-resistant Staphylococcus aureus paradigm.

PMID- 16804375
TI  - Fatal neuroleptic malignant syndrome in a previously long-term user of clozapine
      following its reintroduction in combination with paroxetine.
AB  - A 77-year-old patient with initial behavioral and psychological symptoms of
      dementia was treated with clozapine (50 mg/daily). Since no clinical benefit was
      apparent, clozapine was discontinued after six weeks and the patient started on
      paroxetine (20 mg/daily). After three weeks on paroxetine, he was given another
      trial of clozapine at a starting dosage of 25 mg/daily. While clozapine had
      previously been well tolerated, this time he rapidly developed fever, mental
      confusion, lethargy, muscle spasms and rigidity. The diagnosis of neuroleptic
      malignant syndrome was delayed, because there was no leukocytosis and serum
      creatine phosphokinase was initially not elevated. Subcutaneous apomorphine was
      then given but, after an initial improvement, the patient developed a multiple
      organ failure syndrome and died.

PMID- 16804378
TI  - Prevention of infection in the intensive care unit.
AB  - PURPOSE OF REVIEW: To review tactics used to prevent intensive care unit
      infections, particularly ventilator-associated pneumonia and catheter-related
      bloodstream infections. RECENT FINDINGS: Health-care-associated infections in the
      intensive care unit are associated with elevated mortality, morbidity, and
      hospital costs, and increasing antibiotic resistance. The US Centers for Disease
      Control and Prevention recently published guidelines for the prevention of
      ventilator-associated pneumonia and catheter-related bloodstream infections.
      Though not generally recommended, selective decontamination of the digestive
      tract, an antibiotic prophylaxis strategy, consistently demonstrates reduction in
      ventilator-associated pneumonia rates and mortality but its broader use is
      limited by concerns of increasing resistance. The continued positive results from
      selective decontamination of the digestive tract require that this strategy
      receive significant attention in future studies. Regarding catheter-related
      bloodstream infections, the recommendations suggest education should be used to
      reduce infection rates, but it is likely that the impact of these directives is
      undervalued. The data demonstrate marked reduction in catheter-related
      bloodstream infections in both Latin America and the USA by employing a very low
      tech intervention of education, performance feedback, and initiating process
      controls. SUMMARY: By preventing infections in the intensive care unit, not only
      is the expected effect to reduce injury related to the disease process, but the
      long-term effect is to also reduce resistance by decreasing the need for
      antibiotics.

PMID- 16804379
TI  - Nosocomial pneumonia.
AB  - PURPOSE OF REVIEW: This review describes the most recent advances in the
      management and prevention of nosocomial pneumonia. The new ATS guidelines in
      particular are most likely to affect clinical practice outside the USA. RECENT
      FINDINGS: The problem of multidrug-resistant bacteria causing nosocomial
      pneumonia seems to be increasing. This is particularly true for methicillin
      resistant Staphylococcus aureus. While the diagnosis of ventilator associated
      pneumonia remains a conflictive issue, serial tracheobronchial aspirates may
      improve the selection of adequate antimicrobial treatment. Combined beta-lactam
      and aminoglycoside therapy is inferior to beta-lactam monotherapy, both in terms
      of clinical outcome and in the prevention of resistance during treatment; in
      addition, it carries an increased risk of nephrotoxicity. SUMMARY: The updated
      ATS guidelines will considerably impact clinical approaches to nosocomial and
      healthcare-related pneumonia. Serial tracheobronchial aspirates can be used to
      guide selection of antimicrobial treatment in ventilator associated pneumonia.
      The combination of beta-lactams and aminoglycosides is likely to be abandoned in
      the future. New potent treatment options for pneumonia due to nonfermenters are
      urgently needed.

PMID- 16804380
TI  - Staphylococcal colonization and infection: homeostasis versus disbalance of human
      (innate) immunity and bacterial virulence.
AB  - PURPOSE OF REVIEW: This review identifies trends in the study of interactions
      between Staphylococcus aureus and humans. When nasal colonization is in the
      neutral state, infection clearly represents a state of host-pathogen disbalance.
      The features leading from apparent homeostatic colonization to pathogenesis are
      identified at an increasing rate. RECENT FINDINGS: Persistent carriage of S.
      aureus predisposes to infection but limits bacteraemia-associated mortality.
      Intermittent carriage is usually imposed and of lesser clinical relevance. The
      nature and function of several staphylococcal virulence factors have been
      elucidated and near complete gene catalogues have been established. There does
      not seem to be a difference in virulence, however, between methicillin
      susceptible and resistant S. aureus. Biological selection takes place in the nose
      and innate immune features relevant to colonization have been discovered.
      Acquired immunity remains underexposed, but the host factors involved in the host
      pathogen interaction have been identified. SUMMARY: Virulence assessment of S.
      aureus has been facilitated by novel technology: genome-wide inventories of
      virulence potential can be made and new pathogenic mechanisms have been
      presumptively identified. These involve invasion procedures but also (innate)
      immune evasion strategies. These cross-fertilizing developments shed light on the
      feasibility of novel prophylactic or therapeutic strategies for combating
      staphylococcal carriage and disease.

PMID- 16804381
TI  - Cardiac device infections: getting to the heart of the matter.
AB  - PURPOSE OF REVIEW: Use of electrophysiologic devices (permanent cardiac pacemaker
      and implantable cardioverter/defibrillator) has been increasing. Infection of
      these cardiac devices is a devastating complication, and medical treatment alone
      without device removal is often unsuccessful and frequently leads to infection
      relapse. This article reviews recent publications that address the diagnosis and
      management of infected electrophysiologic devices. RECENT FINDINGS: Recent
      studies have shed new light on the incidence, risk factors, management, and
      outcome of cardiac device infection. Rates of both cardiac device implantation
      and infection have been increasing, although the rate of increase of cardiac
      device infection has outdistanced that of implantation and this has had enormous
      economic and clinical consequences. SUMMARY: The large majority of cardiac device
      infections are likely due to pocket site contamination at the time of device
      placement. Hematogenous seeding from a distant focus of infection, particularly
      due to Staphylococcus aureus, can account for late-onset infection. Although no
      prospective studies have been conducted to date, management with parenteral
      antibiotics and complete device removal is the current standard of care. Further
      study is needed to better define optimal diagnostic and management interventions,
      particularly in patients with bloodstream infection and no local chest wall or
      echocardiographic evidence of cardiac device infection.

PMID- 16804382
TI  - Infections associated with orthopedic implants.
AB  - PURPOSE OF REVIEW: We review recent advances in the prevention, diagnosis and
      treatment of infections associated with joint prostheses and internal fixation
      devices. RECENT FINDINGS: The perioperative antimicrobial prophylaxis should be
      administered 60-30 min before incision or before inflation of the tourniquet. New
      diagnostic approaches include sonication of removed implants to dislodge adherent
      microorganisms growing in biofilms and the use of molecular techniques to improve
      diagnostic yield. Treatment of implant-associated infections without removal of
      the device is an established option for selected patients. Treatment with
      rifampin combinations in staphylococcal infections is crucial for success. As
      demonstrated in vitro, in animal studies and in clinical trials, quinolones are
      suitable combination agents with rifampin against susceptible staphylococci, but
      increasing antimicrobial resistance requires evaluation of alternative
      combination agents, such as quinpristin-dalfopristin, linezolid, and daptomycin,
      although clinical experience is limited. New antimicrobial agents, such as
      dalbavancin, tigecycline, iclaprim, and novel rifamycin derivatives are studied.
      SUMMARY: Better understanding of the interaction between microorganisms, the
      implant and the host may improve our current approach to the diagnosis and
      treatment of implant-associated infections. The treatment modality depends on
      duration of infection, stability of the implant, antimicrobial susceptibility of
      the pathogen and condition of the surrounding soft tissue.

PMID- 16804383
TI  - Is combination therapy indicated for invasive fungal infections? Yes and no.

PMID- 16804384
TI  - Animal models testing monotherapy versus combination antifungal therapy: lessons
      learned and future directions.
AB  - PURPOSE OF REVIEW: The continued rise in serious fungal infections and rises in
      therapy failure dictate that more efficacious therapies be developed. Combination
      therapy using available drugs is an attractive choice, yet primarily only
      anecdotal clinical data are available. We review here data from animal models as
      an indicator of future potential. RECENT FINDINGS: The primary data are from
      murine studies and we will briefly review chemotherapeutic combination studies,
      some showing benefit over monotherapy and some showing no benefit over
      monotherapy. In addition, we will address the potential of immunotherapy in
      combination with conventional therapy. SUMMARY: The data derived from animal
      model studies of antifungal drug efficacy have proven to be predictive of
      clinical utility. Studies on combination therapy will prove useful to the
      clinician in evaluating courses of treatment, especially where clinical-trial
      data are not available or probable in the future.

PMID- 16804385
TI  - Treatment of solid organ transplant patients with invasive fungal infections:
      should a combination of antifungal drugs be used?
AB  - PURPOSE OF REVIEW: Combined antifungal drug therapy is widely used in severe
      invasive mycoses in solid organ transplant (SOT) recipients. We have reviewed the
      available data in the literature. RECENT FINDINGS: No single randomized study on
      antifungal combination therapy in SOT patients has been performed. Existing
      information does not support the use of combination therapy in invasive
      candidiasis in SOT patients. Indeed, initial combination therapy with
      amphotericin B and 5-flucytosine is recommended for SOT patients with central
      nervous system cryptococcosis, mainly with increased white blood cell counts in
      the cerebrospinal fluid or with altered mental status. No impact on outcome was
      observed with combination therapy in Scedosporium infections in SOT patients. The
      combination of voriconazole and terbinafine may be an attractive option for S.
      prolificans infections. A prospective study of voriconazole plus caspofungin as
      initial therapy for invasive aspergillosis in SOT patients found that combination
      therapy was independently associated with reduced mortality in patients with
      renal failure and in those with Aspergillus fumigatus infection, even when
      adjusted for other factors predictive of mortality in the study population.
      SUMMARY: Combination therapy should be considered for severe forms of invasive
      fungal infections in SOT patients; however, multicenter studies of such patients
      are urgently needed.

PMID- 16804386
TI  - Is combination antifungal therapy for invasive aspergillosis a necessity in
      hematopoietic stem-cell transplant recipients?
AB  - PURPOSE OF REVIEW: The use of combination antifungal therapy in hematopoietic
      stem-cell transplantation patients is controversial and limited by a paucity of
      controlled data. The recent literature is reviewed and the relative arguments for
      and against combination antifungal therapy are outlined with summative
      recommendations to assist practitioners in decision-making. RECENT FINDINGS:
      There is an abundance of in-vitro and murine in-vivo combination antifungal
      literature, whereas clinical data are less abundant and controlled. Of the
      published case series there is a suggested benefit to combination therapy over
      monotherapy, although there are limitations to the available literature. Other
      issues in the combination debate that are addressed include the following:
      improved response rates and a survival advantage have been demonstrated in recent
      monotherapy studies; response rates in most published combination therapy studies
      do not suggest large gains over monotherapy; the lack of sustained survival
      advantage to combination therapy studies; and finally the consideration of host
      defenses in treatment responses. SUMMARY: Based on available data, combination
      therapy is not warranted at the initial diagnosis of invasive aspergillosis.
      Randomized, controlled trials with rigorous study design are needed.

PMID- 16804388
TI  - Bibliography. Current world literature. Nosocomial and hospital-related
      infections.

PMID- 16804387
TI  - The rationale of combination antifungal therapy in severely immunocompromised
      patients: empiricism versus evidence-based medicine.
AB  - PURPOSE OF REVIEW: Despite expansion of the antifungal armamentarium over the
      past decade, the mortality rate for invasive fungal infections remains high in
      severely immunocompromised patients. Furthermore, in recent years, difficult-to
      treat invasive infections caused by rare molds and yeasts have emerged in high
      risk patients receiving antifungal prophylaxis or empirical treatment. Antifungal
      combinations are increasingly used in clinical practice to improve outcomes for
      refractory mycoses because of the suboptimal efficacy of current antifungal
      agents. Herein we review recent advances in the area of antifungal combinations
      in high-risk patients to separate empiricism from evidence-based medicine. RECENT
      FINDINGS: Thus far, the benefits of combination antifungal therapy have been
      difficult to prove for invasive fungal infections other than cryptococcal
      meningitis. The recent introduction of a new class of antifungal agents (the
      echinocandins) and extended-spectrum triazoles has rejuvenated interest in
      studying those combinations for difficult-to-treat aspergillosis, as recent
      observational studies show promise. SUMMARY: In view of the evolving epidemiology
      of invasive fungal infections, combination antifungal therapy could be most
      valuable in preemptive management of carefully selected high-risk patients;
      however, this should be studied in appropriate trials.

PMID- 16804389
TI  - Oral mesalamine and clinical remission are associated with a decrease in the
      extent of long-standing ulcerative colitis.
AB  - OBJECTIVE: To compare colonoscopy alone with surveillance biopsy for the
      determination of anatomic extent in long-standing ulcerative colitis (UC). To
      assess the influences of mesalamine use and clinical disease activity on the
      change of histologic extent with time. MATERIALS AND METHODS: Disease extent
      (proctosigmoiditis, left-sided colitis, or pancolitis) measured by colonoscopy
      and surveillance biopsy was compared among 212 consecutive patients with long
      standing UC. Among the 102 patients who had 2 consecutive colonoscopies with
      surveillance biopsies, the following influences on change in histologic extent
      were determined: disease activity, mesalamine use, age at disease onset, folic
      acid, corticosteroid and azathioprine/6-mercaptopurine use, and time between
      colonoscopies. RESULTS: Agreement between gross and microscopic findings was poor
      (kappa = 0.39). Colonoscopy underestimated and overestimated extent in 25.9% and
      8.5%, respectively. Microscopic distribution between consecutive colonoscopies
      remained the same in 60.8%. Where distribution changed, an increase was twice as
      common as a decrease in extent. There was no difference in age at onset, time
      between colonoscopies, or disease duration among those with an increase,
      decrease, or no change in extent. Clinical remission and oral mesalamine were
      independently associated with 10.7 and 5.8 times the odds of a decrease in
      disease extent, respectively. Folic acid, topical mesalamine, corticosteroids,
      and immunomodulators did not influence change in extent. CONCLUSIONS: UC extent
      is best determined by surveillance biopsy. Among patients with long-standing UC,
      histologic extent fluctuates with time. Disease remission and oral mesalamine
      were independently associated with decreases in disease extent.

PMID- 16804390
TI  - Ulcerative colitis and clinical course: results of a 5-year population-based
      follow-up study (the IBSEN study).
AB  - BACKGROUND: The majority of studies concerning the clinical course and prognosis
      in ulcerative colitis (UC) are old, retrospective in design, or hospital based.
      We aimed to identify clinical course and prognosis in a prospective, population
      based follow-up study MATERIALS AND METHODS: Patients diagnosed with inflammatory
      bowel disease (IBD) or possible IBD in southeastern Norway during the period 1990
      1994 were followed prospectively for 5 years. The evaluation at 5 years included
      an interview, clinical examination, laboratory tests, and colonoscopy. RESULTS:
      Of 843 patients diagnosed with IBD, 454 patients who had definite UC and for whom
      there were sufficient data for analysis were alive 5 years after inclusion in the
      study. The frequency of colectomy in this population was 7.5%. Forty-one percent
      of the patients were not taking any kind of medication for IBD at 5 years. Of the
      patients initially diagnosed with proctitis, 28% had progressed during the
      observation period, 10% to extensive colitis. The majority of the patients (57%)
      had no intestinal symptoms at 5 years, and only a minority (7%) had symptoms that
      interfered with everyday activities. Among the patients who underwent colonoscopy
      at the 5-year visit, symptoms were frequently reported in patients without
      macroscopic inflammation (44%). A relapse-free course was observed in 22% of the
      patients. A decrease in symptoms during the follow-up period was the most
      frequent course taken by the disease and was observed in 59% of the cases. The
      extent of disease was unrelated to symptoms at 5 years and also to relapse rate
      and course of disease during the 5-year period. CONCLUSIONS: The disease course
      and prognosis of UC appears better than previously described in the literature.
      The frequency of surgery was low, and only a minority of the patients had
      symptoms that interfered with their everyday activities 5 years after diagnosis.

PMID- 16804391
TI  - A simple biological score for predicting low risk of short-term relapse in
      Crohn's disease.
AB  - BACKGROUND: In Crohn's disease, studies have evaluated the ability of biological
      markers to predict relapse in the next 12 to 18 months, without differentiating
      early from late relapses. The aim of this study was to look for biological
      markers of short-term relapse. MATERIALS AND METHODS: In a previous therapeutic
      trial, patients with a medically induced clinical remission had biological
      markers evaluated and updated every 6 weeks. A Cox model with time-dependent
      covariates was used for analysis. RESULTS: Among the 71 patients, 38 had a
      relapse. Multivariate analysis selected 2 markers predictive of relapse: C
      reactive protein >20 mg/L and erythrocyte sedimentation rate >15 mm. A binary
      biological predictive score was derived: "negative" when both were lower than
      their limits, "positive" when otherwise. The relative risk of short-term relapse
      for patients with a positive score compared to those with a negative score was
      8.0 (95% confidence interval 2.8-22.9). Sensitivity of the score was 89% and
      specificity was 43%. Assuming a 10% relapse rate every 6 weeks, negative and
      positive predictive values were 97% and 15%, respectively. CONCLUSIONS: This
      simple biological score can predict short-term maintenance of remission in
      Crohn's disease and may help physicians in the follow-up of patients in clinical
      remission.

PMID- 16804392
TI  - A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients
      with active moderate to severe Crohn's disease.
AB  - BACKGROUND: Intestinal inflammation associated with Crohn's disease is
      characterized by a type 1 helper T cell response and elevated levels of
      interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL
      23 inhibitor (STA 5326) for the treatment of active Crohn's disease. MATERIALS
      AND METHODS: We conducted an open-label, dose-escalating trial of the orally
      delivered small molecule immunomodulator STA 5326 in 73 patients with active
      Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five
      cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid),
      35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study
      included safety and improvement in clinical activity measured by the CDAI and the
      Crohn's disease endoscopic index of severity. RESULTS: STA 5326 was well
      tolerated. Reported adverse events were similar across dose cohorts. The most
      common (>15%) drug-related adverse events observed were dizziness, nausea,
      headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of
      28 mg and above for the clinical endpoints of response and remission: 70 points
      or greater decrease in CDAI (range 42%-82% of patients); 100 points or greater
      decrease in CDAI (range 38%-64% of patients), and CDAI <150 (range 15%-36%).
      CONCLUSIONS: Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses
      up to 70 mg qd in patients with active moderate to severe Crohn's disease.
      Clinical activity was observed at qd doses of 28 mg and above.

PMID- 16804393
TI  - Fecal S100A12: a novel noninvasive marker in children with Crohn's disease.
AB  - BACKGROUND: The calcium-binding protein S100A12 is related to calprotectin, a
      protein shown to be a useful marker of gut inflammation. S100A12 levels are
      elevated in serum and mucosa of children with inflammatory bowel disease (IBD)
      and may be implicated in the pathogenesis of IBD. The aims of this study were to
      validate an immunoassay for the detection of fecal S100A12, to assess its value
      as a new noninvasive marker of gut inflammation, and to investigate S100A12
      levels in feces of children with IBD at diagnosis and during treatment. MATERIALS
      AND METHODS: Feces were collected from children with active IBD at diagnosis and
      during treatment for IBD and from normal healthy control subjects. Fecal and
      serum levels of S100A12 were measured by immunoassay. RESULTS: A sensitivity of
      96% and a specificity of 92% were observed when 10 mg/kg fecal S100A12 was used
      as a cutoff. S100A12 levels were evenly distributed throughout fecal samples and
      were stable for 7 days when stored at room temperature. Fecal S100A12 was
      elevated in children with IBD compared with healthy control subjects, with levels
      closely correlated to disease activity and other serum inflammatory markers,
      particularly lower gut involvement. Fecal S100A12 levels fell during therapy in
      children entering remission with normal C-reactive protein levels. CONCLUSIONS:
      Fecal S100A12 is a novel noninvasive marker that distinguishes children with
      active IBD from healthy control subjects with high sensitivity and specificity.
      Fecal S100A12 possesses characteristics that are desirable for a noninvasive
      disease marker and therefore is a suitable candidate marker for IBD. Further
      evaluation is required to examine this marker in additional contexts.

PMID- 16804394
TI  - Reactive hemophagocytic syndrome complicating the treatment of inflammatory bowel
      disease.
AB  - BACKGROUND AND AIMS: Reactive hemophagocytic syndrome (RHS) is a rare disease in
      which inappropriately activated macrophages consume bone marrow-derived cells.
      Most cases are associated with infection in the setting of immunodeficiency. The
      widespread use of immunosuppressive therapy in the treatment of inflammatory
      bowel disease (IBD) places patients with Crohn's disease and ulcerative colitis
      at risk of this complication. No concerted effort has been made to alert
      gastroenterologists of this condition, and treatment recommendations are lacking.
      The aims of this study were to describe the clinical and laboratory features of
      RHS associated with IBD and to review diagnostic criteria, treatment options, and
      pathogenesis. MATERIALS AND METHODS: Clinical and laboratory data were pooled
      from the clinical practice of the investigators and from published cases.
      Descriptive statistics were performed. RESULTS AND CONCLUSIONS: Seven cases of
      RHS complicating the treatment of IBD were identified. All patients were on
      immunosuppressive therapy, with nearly half taking >1 agent. All patients
      presented with fever, leukopenia, anemia, and hyperferritinemia. Infection by a
      member of the herpesvirus family or an intracellular pathogen precipitated RHS in
      6 of 7 patients. The mortality rate was 29%. The diagnosis of RHS should be
      considered in patients with IBD taking immunosuppressive therapy who present with
      fever and cytopenia. Evaluation should begin with a serum ferritin. In patients
      with a serum ferritin > or =10,000 ng/mL, a bone marrow biopsy should be
      performed to confirm hemophagocytosis. If the initial evaluation is negative,
      then clinical suspicion should be maintained until the episode resolves.

PMID- 16804395
TI  - A new transcription factor that regulates TNF-alpha gene expression, LITAF, is
      increased in intestinal tissues from patients with CD and UC.
AB  - BACKGROUND: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)
      plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative
      colitis (UC). Recently, a new transcription factor termed LITAF
      (lipopolysaccharide-induced TNF-alpha factor) was shown to mediate TNF-alpha
      expression in human macrophages by direct binding to specific sequences in the
      promoter region of the TNF-alpha gene. METHODS: In this report, we identified
      LITAF in resected ileal and colonic tissues from patients with CD and UC by
      immunohistochemistry, real-time polymerase chain reaction, and Western blot
      analysis. LITAF expression in inflamed and noninflamed areas of the tissues was
      compared. RESULTS: This is the first demonstration of LITAF, a newly discovered
      transcription factor that regulates TNF-alpha gene transcription in ileal and
      colonic tissues from patients with either CD or UC. LITAF immunostaining was
      localized to lamina propria macrophages and was markedly increased relative to
      tissues from controls without inflammatory bowel disease. In patients with CD, a
      5-fold increase in LITAF mRNA was measurable in noninflamed colonic tissues
      compared with controls without inflammatory bowel disease. LITAF mRNA in tissues
      from inflamed areas of the colon was increased by an additional 60% compared with
      noninflamed tissues. In patients with UC, LITAF mRNA levels in colonic tissues
      resected from noninflamed areas were elevated 15-fold above nondisease controls,
      but they were not different in tissues resected from inflamed areas. Western blot
      analysis showed that in patients with CD, there was a marked increase in LITAF
      protein in inflamed areas compared with noninflamed areas. LITAF protein levels
      were not different between noninflamed and inflamed tissues obtained from
      patients with UC. TNF-alpha mRNA and protein levels paralleled LITAF. Similarly,
      in inflamed ileal tissues from patients with CD, LITAF is also localized to
      lamina propria macrophages. LITAF mRNA and LITAF protein were significantly
      increased in inflamed ileal tissues compared with noninflamed areas. CONCLUSIONS:
      LITAF is readily detectable in ileal and colonic tissues from patients with
      either CD or UC, is significantly elevated above controls, and is localized to
      macrophages, a major source of TNF-alpha. These data provide strong evidence of a
      role for LITAF in the pathophysiological regulation of the TNF-alpha gene and
      underscore the potential value of anti-LITAF strategies in the clinical
      management of these diseases.

PMID- 16804396
TI  - Galectin-3 modulates T cell activity and is reduced in the inflamed intestinal
      epithelium in IBD.
AB  - BACKGROUND: Galectins are involved at different stages in inflammation. Galectin
      3, although mostly described as proinflammatory, can also act as an
      immunomodulator by inducing apoptosis in T cells. The present study aims to
      determine galectin-3 expression in the normal and inflamed intestinal mucosa and
      to define its role in T cell activity. MATERIALS AND METHODS: Galectin-3 was
      detected by quantitative polymerase chain reaction with total RNA from endoscopic
      biopsies and by immunohistochemistry. Biopsies and peripheral blood mononuclear
      cells (PBMC) were stimulated in vitro and were used to assess the functional
      consequences of inhibition or exogenous addition of galectin-3. RESULTS: Galectin
      3 is expressed at comparable levels in controls and inflammatory bowel disease
      (IBD) patients in remission. In the normal mucosa, galectin-3 protein was mainly
      observed in differentiated enterocytes, preferentially at the basolateral side.
      However, galectin-3 was significantly downregulated in inflamed biopsies from IBD
      patients. Ex vivo stimulation of uninflamed biopsies with tumor necrosis factor
      led to similar galectin-3 messenger RNA downregulation as in vivo. When
      peripheral blood mononuclear cells (PBMC) were analyzed, galectin-3 was mainly
      produced by monocytes. Upon mitogen stimulation, we observed increased
      proliferation and decreased activation-induced cell death of peripheral blood T
      cells in the presence of galectin-3-specific small interfering RNA. In contrast,
      exogenous addition of recombinant galectin-3 led to reduced proliferation of
      mitogen-stimulated peripheral blood T cells. CONCLUSIONS: Our results suggest
      that downregulation of epithelial galectin-3 in the inflamed mucosa reflects a
      normal immunological consequence, whereas under noninflammatory conditions, its
      constitutive expression may help to prevent inappropriate immune responses
      against commensal bacteria or food compounds. Therefore, galectin-3 may prove
      valuable for manipulating disease activity.

PMID- 16804398
TI  - Role of the NFKB1 -94ins/delATTG promoter polymorphism in IBD and potential
      interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes.
AB  - BACKGROUND: Recently, an association of the NFKB1 polymorphism -94ins/delATTG
      with ulcerative colitis (UC) has been reported. This 4-bp insertion/deletion
      polymorphism is localized in the promoter region of the NFKB1 gene and appears to
      be functionally relevant. The aim of the present study was to confirm the
      association of the -94ins/delATTG (W/D) NFKB1 promoter polymorphism with UC in a
      population of German origin and to test for a potential association with Crohn's
      disease (CD). Furthermore, potential interactions of the -94ins/delATTG
      polymorphism with the IKBL and the IL-1RN genes should be determined. MATERIALS
      AND METHODS: The study population comprised 630 patients with CD, 365 patients
      with UC, and 974 healthy controls. Genotyping was performed using polymerase
      chain reaction and restriction fragment length polymorphism analysis. For
      statistical evaluation, the chi-square test and the Fisher exact test were used.
      RESULTS: No significant association of the W/D NFKB1 polymorphism with CD or UC
      was detected. In addition, no significant interactions between the -94ins/delATTG
      NFKB1 polymorphism and polymorphisms within the IKBL and the IL-1RN genes,
      respectively, were found in CD or UC. Also, no significant interactions of the
      NFKB1 polymorphism with mutations of the CARD15/NOD2 gene and with clinical
      phenotypes were detected in CD. Moreover, no associations of the NFKB1
      polymorphism were found in UC depending on disease localization. CONCLUSIONS: The
      present study could not confirm the reported association of the -94ins/delATTG
      NFKB1 polymorphism with UC and also found no evidence for a role of this
      polymorphism in CD. The results do not give evidence for a role of this NFKB1
      polymorphism in the pathogenesis of UC and CD.

PMID- 16804397
TI  - Detection of muramyl dipeptide-sensing pathway defects in patients with Crohn's
      disease.
AB  - BACKGROUND AND AIMS: Crohn's disease is strongly associated with double mutations
      in NOD2/CARD15. Three common mutations (Arg702Trp, Gly908Arg, Leu1007fs) impair
      innate immune responses to bacterial muramyl dipeptide. Rare NOD2 variants occur,
      but it is difficult to both identify them and assess their functional effect. We
      assessed the true frequency of defective muramyl dipeptide sensing in Crohn's
      disease and developed a rapid diagnostic assay. MATERIALS AND METHODS: An ex vivo
      assay was established and validated based on muramyl dipeptide stimulation of
      peripheral blood mononuclear cell cytokine production. Muramyl dipeptide-induced
      enhancement of interleukin (IL)-8 secretion and synergistic increase in
      lipopolysaccharide-induced IL-1beta secretion were studied. Assay results were
      compared with NOD2 genotype status (3 common mutations and rare variants) in 91
      individuals including a prospective cohort of 49 patients with Crohn's disease.
      RESULTS: The assay was highly sensitive and specific for detection of profound
      defects in muramyl dipeptide sensing caused by double NOD2 mutations (IL-8 P =
      0.0002; IL-1beta P = 0.0002). Disease state, active inflammation, or concurrent
      use of immunosuppressive medication did not influence results. Healthy NOD2
      heterozygotes had modest impairment of muramyl dipeptide induced IL-8 secretion
      (P = 0.003). Only 1 of 7 patients with Crohn's disease with both a common
      mutation and a rare variant had a profound muramyl dipeptide-sensing defect.
      CONCLUSIONS: Profound defects in muramyl dipeptide sensing were found in 10% of
      patients with Crohn's disease. Defects were caused exclusively by inherited
      mutations in NOD2. The ex vivo assay has multiple potential applications as a
      clinical diagnostic tool to distinguish patients with muramyl dipeptide-sensing
      defects and for research investigation.

PMID- 16804399
TI  - Chemokines involved in protection from colitis by CD4+CD25+ regulatory T cells.
AB  - Chemokines are small proteins involved in the direction of migration of immune
      cells both during normal homeostasis and inflammation. Chemokines have been
      implicated in the pathology of many different inflammatory disorders and are
      therefore appealing therapeutic targets. Using a chemokine/chemokine receptor
      specific gene expression profiling system of 67 genes, the authors have
      determined the expression profile of chemokine and chemokine receptor genes in
      the rectum of colitic mice and in mice that have been protected fromcolitis by
      CD4CD25 regulatory T cells. In mice protected from colitis, the authors found
      down regulation of the mRNA expression of the inflammatory chemokine receptors
      CCR1 and CXCR3 and their ligands CXCL9, CXCL10, CCL5, and CCL7. Also the
      transcripts for CCR9, CCL25, CCL17, and CXCL1 are found down regulated in
      protected compared with colitic animals. In addition, the authors' results
      suggest that CCL20 is used by CCR6 regulatory T cells in the complex process of
      controlling colitis because transcripts for this chemokine were expressed to a
      higher level in protected animals. The chemokine pathways identified in the
      present study may be of importance for the development of new targets for anti
      inflammatory treatment strategies in human inflammatory bowel disease.

PMID- 16804401
TI  - Amelioration of murine dextran sulfate sodium-induced colitis by ex vivo
      extracellular superoxide dismutase gene transfer.
AB  - BACKGROUND: Although the etiology of inflammatory bowel disease has not been
      fully clarified, reactive oxygen species is speculated to be involved.
      Extracellular superoxide dismutase (EC-SOD), an isozyme of SODs, is known to
      function mainly in body fluids. We investigated the efficacy of an ex vivo EC-SOD
      gene transfer into dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS
      AND METHODS: Experimental colitis was induced by providing Balb/c mice with DSS
      in sterile distilled water provided as desired. The syngenic fibroblasts were
      obtained from Balb/c mice embryos and retrovirally transduced with the hEC-SOD
      gene. These engineered cells were confirmed to secrete EC-SOD in culture medium
      by enzyme-linked immunosorbent assay and were inoculated subcutaneously in the
      backs of DSS-treated mice. Mucosal injury of the colon was evaluated by the
      disease activity index (DAI: body weight, rectal bleeding, and stool
      consistency), grading of histologic disease severity, and levels of cytokine
      (tumor necrosis factor-alpha, interleukin-1beta) production. 8
      Hydroxydeoxyguanosine (8-OHdG) levels in the mucosal tissue were assessed by
      immunohistochemical staining. Malondialdehyde (MDA) was measured using a
      colorimetric assay. RESULTS: A significant improvement was observed in DAI score
      and histologic severity as well as in mucosal tissue levels of inflammatory
      cytokines, 8-OHdG, and MDA of mice treated with the EC-SOD gene as compared with
      those without gene therapy, not only in a mild colitis model but also in a severe
      colitis model. Survival of treated mice in these models was significantly
      prolonged. CONCLUSIONS: Ex vivo transfer of the EC-SOD gene was feasible for
      treatment of DSS-induced colitis.

PMID- 16804402
TI  - Functional consequences of NOD2 (CARD15) mutations.
AB  - Polymorphisms in NOD2 (CARD15) are associated with ileal and ileocolonic Crohn's
      disease, increased mortality from graft-versus-host disease, and Blau syndrome.
      NOD2 activation by peptidoglycan components initiates various signaling pathways
      and CD-associated NOD2 mutations are associated with decreased activation of NF
      kappaB. NOD2 may be important for both initial defenses against commensal and
      pathogenic bacteria and tolerance mechanisms for maintaining controlled
      activation of the intestinal immune system. Significant progress has been made in
      defining NOD2 signaling partners and pathways and functional consequences of NOD2
      mutations with respect to its activation, expression, signaling, synergistic
      effects with Toll-like receptor signaling, and antimicrobial effects. However,
      NOD2 contributions to human intestinal inflammation are complex and incompletely
      understood. Improved understanding of NOD2-mediated pathways may lead to
      identification of other molecules that can also contribute to the development of
      Crohn's disease in humans.

PMID- 16804400
TI  - Gliotoxin reduces the severity of trinitrobenzene sulfonic acid-induced colitis
      in mice: evidence of the connection between heme oxygenase-1 and the nuclear
      factor-kappaB pathway in vitro and in vivo.
AB  - BACKGROUND: Gliotoxin, a fungal metabolite, has been known to show strong
      immunosuppressive properties, although its mechanisms are not completely
      understood. In this report, the authors investigated the mechanism whereby
      gliotoxin has anti-inflammatory properties in vitro and in trinitrobenzene
      sulfonic acid-induced colitis. MATERIALS AND METHODS: Body weight, histological
      scores, and myeloperoxidase activity were evaluated in trinitrobenzene sulfonic
      acid colitis. Nuclear factor-kappaB (NF-kappaB) p65, tumor necrosis factor-alpha,
      interleukin (IL)-1beta, IL-12, and intercellular adhesion molecule-1 were
      detected by immunohistochemical staining. IL-8 secretion was measured by an
      enzyme-linked immunosorbent assay. Heme oxygenase-1 (HO-1) expression and I
      kappaB degradation were analyzed by Western blot. RESULTS: Pretreatment of human
      epithelial HT-29 cells with gliotoxin significantly blocked the I-kappaB
      degradation and NF-kappaB p65 nuclear translocation induced by tumor necrosis
      factor-alpha or IL-1beta; these were parallel with the inhibition of IL-8
      secretion and intercellular adhesion molecule-1 expression in the same cells.
      Interestingly, gliotoxin induced HO-1 in HT-29 cells and, in turn, inhibition of
      HO-1 activity by a zinc protoporphyrin IX reversed the effects of gliotoxin in
      terms of I-kappaB degradation, intercellular adhesion molecule-1 expression, and
      IL-8 production. In trinitrobenzene sulfonic acid colitis, gliotoxin
      administration significantly improved the clinical and histopathological
      symptoms. Notably, gliotoxin also induced HO-1 in the colonic mucosa and zinc
      protoporphyrin IX reversed the protective effects of gliotoxin in trinitrobenzene
      sulfonic acid colitis. CONCLUSIONS: These results demonstrate for the first time
      that the anti-inflammatory actions mediated by gliotoxin include HO-1 induction
      and the subsequent blockade of NF-kappaB-dependent signaling pathways in vitro
      and in vivo. The current results also demonstrate that gliotoxin may be an
      effective agent for the treatment of diseases characterized by mucosal
      inflammation.

PMID- 16804403
TI  - Use of antibiotics in the treatment of inflammatory bowel disease.
AB  - An increasing amount of evidence suggests that enteric flora may have a role in
      the pathogenesis of inflammatory bowel disease (IBD). Patients with IBD appear to
      have an altered composition of luminal bacteria that may provide the stimulus for
      the chronic inflammation characterizing IBD. The suspected role of bacteria in
      the pathogenesis of IBD provides the rationale for using agents, such as
      antibiotics, that alter the intestinal flora. However, there remains much
      uncertainty about the optimal use of antibiotics in the treatment of Crohn's
      disease, ulcerative colitis, and pouchitis. This article reviews the literature
      and presents a clinical model for the use of antibiotics in IBD.

PMID- 16804404
TI  - A role for STAT5 in steroid-resistant UC?

PMID- 16804405
TI  - Liver abscesses as the presenting manifestation of Crohn's disease in an
      adolescent.

PMID- 16804406
TI  - Somatostatin and its receptors in the development of the endocrine pancreas.
AB  - The development of the endocrine pancreas is regulated by numerous transcription
      and growth factors. Somatostatin (SST) is present in many tissues and acts as a
      neurotransmitter and autocrine/paracrine/endocrine regulator in response to ions,
      nutrients, peptides, and hormones as well as neurotransmitters. In the pancreas,
      there is evidence that SST acts an inhibitory paracrine regulator of hormone
      secretion. Somatostatin receptors (SSTRs) are a family of 5 transmembrane G
      protein-coupled receptors, which are widely expressed in mammals including
      humans. SSTRs regulate multiple downstream signal transduction pathways that
      mediate inhibitory effects. These receptors also exhibit age- and tissue-specific
      expression patterns. Interactions of SST and SSTRs are not only important during
      normal pancreas development, but have also been implicated in many pancreatic
      diseases such as diabetes mellitus and pancreatic cancer. In this review article,
      we use evidence from recently published animal studies to present the critical
      roles of SST and SSTRs proteins in the development of the endocrine pancreas.

PMID- 16804407
TI  - The Japanese diagnostic criteria for autoimmune chronic pancreatitis: is it
      completely satisfactory?
AB  - OBJECTIVES: Autoimmune chronic pancreatitis (AIP) is a very attractive disease to
      clinicians in terms of its dramatic response to the oral steroid therapy in
      contrast to ordinary chronic pancreatitis. In the year 2002, the Japan Pancreas
      Society published the diagnostic criteria of AIP, and many clinicians around the
      world use these criteria for its diagnosis. The purpose of this study was to
      evaluate whether the Japanese criteria for the diagnosis of AIP are adequate or
      not. METHODS: We retrospectively analyzed the clinical, radiologic, laboratory,
      and histologic features of 31 patients with AIP who have been successfully
      treated with oral corticosteroid. All the enrolled patients showed normalization
      or marked improvement in symptoms, laboratory, and imaging findings after steroid
      treatment. RESULTS: The mean patients' age was 56 years (range, 32-78 years) and
      comprised 25 males and 6 females. Seven patients who responded to the steroid did
      not satisfy the Japanese imaging criterion because the extent of irregular
      narrowing was less than one third of the entire length of main pancreatic duct.
      Among these 7 patients, 1 patient did not meet the laboratory and histopathologic
      criteria as well. Another 2 patients fulfilled the Japanese imaging criterion
      only and showed normal IgG level, negative results of autoantibody measurements,
      and nondiagnostic pancreatic histopathology. Taken together, 9 (29%) of the 31
      patients did not meet the Japanese diagnostic criteria for AIP, yet responded to
      the steroid. CONCLUSIONS: Clinicians may miss a substantial portion of AIP
      patients who may benefit from steroid therapy when the diagnosis is confined to
      those who satisfy the criteria proposed by the Japan Pancreas Society. It is
      necessary to convene a worldwide consensus to develop an improved diagnostic
      criteria for AIP.

PMID- 16804408
TI  - Identification of a novel autoantibody against pancreatic secretory trypsin
      inhibitor in patients with autoimmune pancreatitis.
AB  - OBJECTIVES: Although autoimmune pancreatitis (AIP) has been recently recognized
      as a new disease entity of chronic pancreatitis, the clinical diagnosis of the
      disease remains disputed. Autoantibodies against carbonic anhydrase II and
      lactoferrin are detected in most patients with AIP, but not in about 10%. We
      undertook this study to determine whether additional autoantibodies are present
      in the serum level of AIP patients. METHODS: We recruited 26 patients with AIP
      for the study. For comparison, we also recruited 53 patients with various
      pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic
      cDNA library using patients' sera. Positive clones were analyzed by DNA
      sequencing and were constructed into a pGEX-4T-1 expression vector. The
      recombinant proteins were used as antigens in enzyme-linked immunosorbent assay
      to screen the subjects' sera for autoantibodies. RESULTS: We cloned a cDNA
      encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients
      with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%)
      by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay,
      respectively. However, none of control subjects was positive for anti-PSTI
      antibodies. CONCLUSIONS: These findings suggest that PSTI may be related to the
      pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic
      marker for the disease.

PMID- 16804409
TI  - Admission serum glucose level: an accurate predictor of outcome in gallstone
      pancreatitis.
AB  - OBJECTIVES: Early identification of patients at high risk of complications from
      acute pancreatitis is important; as yet, no simple and accurate method has been
      identified. The aim was to evaluate admission serum glucose as a prognostic
      marker in gallstone pancreatitis. METHODS: Retrospective review of consecutive
      admissions with gallstone pancreatitis to a large urban hospital was made. Serum
      glucose levels, Glasgow scores, and Acute Physiology and Chronic Health
      Evaluation (APACHE) II scores were recorded. Outcomes considered were death,
      intensive care requirement, local complications, and length of hospital stay.
      RESULTS: There was a total of 184 admissions (122 women and 62 men; mean age,
      55.4 years). Serum glucose of 8.3 mmol/L or higher was as good as APACHE II score
      of 8 or above (likelihood ratios [LRs] of 2.51 and 2.84, respectively) in
      predicting mortality (overall probability, 4.3%). Overall, 9.2% of the patients
      were admitted to intensive care units, and risk was significantly higher in
      patients with glucose of 8.3 mmol/L or higher (LR, 3.23; P < 0.001) or APACHE II
      score of 8 or above (LR, 1.9; P < 0.02). Local complications occurred in 12.0% of
      the patients, and the risk significantly increased in patients with glucose of
      8.3 mmol/L or higher (LR, 2.61; P < 0.001) but not for APACHE II or Glasgow
      scores. Patients with admission serum glucose of 8.3 mmol/L or higher had a mean
      length of stay of 17.9 days as compared with 7.1 days for patients with admission
      serum glucose of less than 8.3 mmol/L (P < 0.001). CONCLUSIONS: In gallstone
      pancreatitis, an elevated admission serum glucose level offers more prognostic
      information than Glasgow and APACHE II scores.

PMID- 16804411
TI  - Aberrant expression of PTCH (patched gene) and Smo (smoothened gene) in human
      pancreatic cancerous tissues and its association with hyperglycemia.
AB  - OBJECTIVES: To investigate the prevalence of PTCH (patched gene) and Smo
      (smoothened gene) expression in human pancreatic cancerous tissues and its
      association with clinical characteristics. METHODS: A rabbit polyclonal antibody
      against PTCH was prepared through the immunization of prokaryotic recombinant
      PTCH1170-1433 protein. The PTCH and Smo expression in 39 resected pancreas
      specimens from 28 patients with pancreatic cancer, 6 with chronic pancreatitis
      (as control), and 5 with pancreatic pseudocyst (as control) were detected by
      reverse transcriptase polymerase chain reaction and immunohistochemistry. The
      relationships between their expressions and pathological characteristics such as
      tumor sizes, degree of differentiation, nodal status, distant metastasis, and the
      blood sugar level were analyzed. RESULTS: The prevalence of PTCH and Smo
      expressions in cancerous tissues were 71.4% (20/28) and 53.6% (15/28),
      respectively, whereas no expression in the nontumor pancreas tissues was found.
      Both PTCH and Smo expressions correlated with the low levels of tumor tissue
      differentiation (P < 0.05) and PTCH and Smo expressions in islet cells of
      cancerous tissues associated with hyperglycemia. CONCLUSIONS: Because aberrant
      expressions of PTCH and Smo were common in human pancreatic carcinoma tissues and
      were associated with the low-level differentiation of tumor tissue and
      hyperglycemia, this indicated that these molecules played a fundamental role in
      pancreas tumorigenesis and were regarded as new targets for diagnosis and
      treatment of human pancreatic cancer.

PMID- 16804410
TI  - Clinical monitoring of innate cellular immunity of monocytes/macrophages by tumor
      necrosis factor alpha productivity in whole blood stimulated by
      lipopolysaccharide in patients with pancreatic cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the tumor necrosis factor alpha
      (TNF-alpha) releasing capacity in whole blood stimulated by lipopolysaccharide
      (LPS) in patients with pancreatic cancer during the perioperative period, and
      before and after chemotherapy. METHODS: The current study involved a total of 39
      patients with pancreatic cancer (PC), who were further divided into a PC-Op group
      (n = 16, underwent pancreatectomy) and a PC-chemo group (n = 23, received
      chemotherapy). The control groups consisted of patients with hepatocellular
      carcinoma (n = 27, HCC group) and with benign diseases (n = 15, control group).
      Serial changes in TNF-alpha in whole blood stimulated by LPS were compared in
      various clinical settings. RESULTS: Preoperative TNF-alpha levels in the PC-Op
      group were significantly lower than those in the HCC and control groups (P =
      0.034). The TNF-alpha variable surgical index (s-index) was defined as the ratio
      of the preoperative TNF-alpha level to postoperative level in the PC-Op and HCC
      groups. Although the TNF-alpha s-index in the PC-Op group was significantly
      decreased on postoperative day 1 and recovered on postoperative day 3 (P <
      0.002), there were no significant changes in the TNF-alpha s-index in the HCC
      group. The TNF-alpha variable chemotherapeutic index (c-index) was defined as the
      ratio of the TNF-alpha level before to that after chemotherapy in the PC-chemo
      group. The TNF-alpha c-index in all 7 patients was reduced to less than 0.3 until
      leukopenia appeared. Patients who had an increase in TNF-alpha production (TNF
      alpha c-index >1.0) on day 3 or 7 after chemotherapy had significantly better
      cumulative survival than those with no increase (P < 0.033). CONCLUSIONS: TNF
      alpha production stimulated by LPS in the whole blood of patients with pancreatic
      cancer was low. Surgical stress and depressed immunocompetence might induce such
      profound decreases. A method of assessing the capability of leukocytes,
      particularly macrophages, to produce TNF-alpha could be useful for prognostis and
      for monitoring immunocompetence in patients with pancreatic cancer who have
      undergone chemotherapy.

PMID- 16804412
TI  - Less morbidity after pancreaticoduodenectomy of patients with pancreatic cancer.
AB  - OBJECTIVES: The pancreaticoduodenectomy with extended resection has been
      frequently performed in patients with pancreatic cancer in Japan. One result of
      this additional surgical stress may be that postoperative complications in
      patients with pancreatic cancer are more frequent than in patients with
      periampullary cancer. METHODS: The 198 patients with pancreatic and periampullary
      cancer underwent pancreaticoduodenectomy. The operative mortality and morbidity
      between patients with pancreatic and periampullary cancer were compared, and the
      risk factors of postoperative complications and in-hospital death were
      determined. RESULTS: Patients with pancreatic and periampullary cancer made up
      52% and 48% of total patients. The duration of surgery and volume of
      intraoperative blood loss were significantly higher in patients with pancreatic
      cancer than in patients with periampullary cancer. Additional organ resections
      were frequently performed in patients with pancreatic cancer. However,
      significantly lower morbidity rates were observed in patients with pancreatic
      cancer. Among all complications evaluated, pancreatic fistula and abdominal
      abscess were found less frequently in patients with pancreatic cancer. Logistic
      regression analyses showed a positive correlation between periampullary cancer
      and an increased risk of complications, pancreatic fistula, and abdominal
      abscess. The in-hospital mortality rate has significantly reduced since 2000.
      When pancreatic fistula was clinically diagnosed, we immediately started a closed
      lavage using continuous administration of natural saline at 1000 to 4000 mL/d,
      after exchange of a nasogastric tube drain. CONCLUSION: Pancreaticoduodenectomy
      for patients with pancreatic cancer can be a safe procedure in spite of surgical
      stress. Further surgical strategies will be needed to reduce postoperative
      complications, especially in patients with periampullary cancer.

PMID- 16804413
TI  - Ethanol and the tobacco-specific carcinogen, NNK, contribute to signaling in
      immortalized human pancreatic duct epithelial cells.
AB  - OBJECTIVES: Smoking is a well-documented risk factor for pancreatic cancer. The
      tobacco-specific nitrosamine, NNK (4-[methylnitrosamino]-1-[3-pyridyl]-1
      butanone), significantly induces pancreatic ductal adenocarcinomas in laboratory
      rodents. Recent observations suggest that ethanol enhances the tumorigenic
      effects of smoking. Ethanol consumption is associated with the development of
      chronic pancreatitis, also considered a predisposing factor for pancreatic ductal
      adenocarcinoma. Because the precise role of ethanol in pancreatic carcinogenesis
      is not known, this study sought to elucidate the cumulative effects of ethanol
      and NNK on particular signal transduction pathways that might play a role in cell
      proliferation in immortalized human pancreatic duct epithelial cells. METHODS:
      The HPDE6-c7 cells are developed from pancreatic duct epithelial cells, which are
      the putative cells of origin of pancreatic ductal adenocarcinoma. Cell
      proliferation assays, Western blot, and cyclic adenosine monophosphate assays
      were used to demonstrate the effects of ethanol and NNK treatments on these
      cells. RESULTS: Ethanol cotreatments enhanced the NNK-induced proliferation of
      these cells. This response was inhibited by the adenylyl cyclase, protein kinase
      A, mitogen-activated protein kinase (p42/p44), and epidermal growth factor
      receptor-specific tyrosine kinase inhibitors. Cotreatments of NNK and ethanol
      also increased cyclic adenosine monophosphate accumulation, cAMP response element
      binding family of proteins and mitogen-activated protein kinase phosphorylation,
      and protein kinase A activation. CONCLUSIONS: These findings suggest a potential
      role for these pathways contributing to the development of smoking- and alcohol
      related pancreatic carcinogenesis.

PMID- 16804414
TI  - Association of SH-2 containing inositol 5'-phosphatase 2 gene polymorphisms and
      hyperglycemia.
AB  - OBJECTIVES: SH-2 containing inositol 5'-phosphatase 2 (SHIP2) is a family of
      inositol 5'-phosphatases, which possess the 5'-phosphatase activity that
      hydrolyzes phosphatidylinositol-3, 4, 5-trisphosphate to phosphatidylinositol-3,
      4-bisphosphate and is suspected to negatively regulates the metabolic signaling
      of insulin. To clarify the possible involvement of SHIP2 in physiological
      abnormalities, we examined the human SHIP2 gene polymorphism in a Japanese
      cohort. METHODS: We searched single-nucleotide polymorphisms (SNPs) on the human
      SHIP2 gene promoter and 5'-untranslated region (5'-UTR) and investigated their
      relationship with impaired fasting glycemia (IFG) in a Japanese cohort. Next, the
      effect of the SNPs on promoter activity was examined in HeLa and HL60 cells.
      RESULTS: Among the several SNPs detected on the human SHIP2 gene promoter and 5'
      UTR, 3 SNPs (-405 C/A, +57 G/A, and +334 C/T) formed the haplotypes CGC and AAT
      and were found at a relatively high frequency in the Japanese population. The
      frequency of genotypes (+334 CT and TT) was significantly higher in the group
      with IFG than in the normal group (P < 0.0001, odds ratio = 2.23, 95% confidence
      interval = 1.50-3.32). This association was not affected by age and gender.
      Furthermore, one haplotype (+57 A, +334 T) which was inserted into a luciferase
      reporter plasmid and existed more frequently in the IFG group than in the normal
      group exhibited increased promoter activity in the culture cells compared with
      the other haplotype (+57 G, +334 C). CONCLUSIONS: The SNPs in the SHIP2 gene
      promoter and the 5'-UTR may account partly for the IFG and may be a marker for
      the risk of diabetes.

PMID- 16804415
TI  - Long-term ethanol consumption alters pancreatic gene expression in rats: a
      possible connection to pancreatic injury.
AB  - OBJECTIVES: Long-term ethanol consumption does not cause acute pancreatitis but
      rather sensitizes the pancreas to subsequent insults. The mechanisms responsible
      for this sensitization are unknown. To determine whether alterations in
      pancreatic gene expression might participate in ethanol-mediated sensitization,
      we performed gene-profiling analysis. METHODS: Animals were fed ethanol
      containing Lieber-DeCarli or control diet (pair-fed). After 8 weeks, pancreatic
      RNA expression was analyzed using Affimetrix GeneChips. Changes in specific genes
      were verified using quantitative reverse transcriptase-polymerase chain reaction.
      RESULTS: Long-term ethanol feeding caused a significant alteration of pancreatic
      gene expression. Selection criteria of changes more than 3-fold and P < 0.05
      yielded 114 probe sets. Activating transcription factor 3, heat shock protein 70,
      heat shock protein 27, and mesotrypsinogen were increased, whereas pancreatitis
      associate protein, folate carrier, and metallothionein were decreased.
      CONCLUSIONS: Ethanol had a profound effect on pancreatic gene expression. The
      genes identified as elevated and reduced in this study may contribute to
      pancreatic sensitivity to stress. This study indicates for the first time the
      identities of multiple genes whose expression levels are dramatically influenced
      by long-term ethanol feeding. The identified genes may help explain the
      relationship between long-term ethanol abuse and pancreatic disease and lead to
      possible preventative or therapeutic approaches to ethanol-induced pancreatic
      disease.

PMID- 16804417
TI  - Solid serous adenoma of the pancreas: a rare variant within the family of
      pancreatic serous cystic neoplasms.
AB  - We report the third case of a solid serous adenoma of the pancreas, a rare
      variant of tumor within the family of pancreatic serous cystic neoplasms. This
      asymptomatic tumor presented in a 66-year-old man during imaging for another
      problem. Computed tomography of the abdomen demonstrated a 3.5-cm hypervascular
      mass in the head of the pancreas. A pylorus preserving pancreaticoduodenectomy
      was performed. Histological examination demonstrated a neoplasm identical to a
      serous cystadenoma-glycogen-rich cuboidal or polygonal cells with finely
      granulated eosinophilic or clear cytoplasm. More often, the neoplasm contained
      solid areas and tubules but no microcysts. Periodic acid Schiff's-glycogen
      staining was positive in some cells, turning negative after diastase was applied.
      Immunostaining was positive for CK7, CK8, neuron specific enolase, and MUC6. The
      microscopic findings of a solid neoplasm of cuboidal cells rich in glycogen and
      the immunostaining listed associate this tumor with the previously 2 reported
      cases of solid serous adenoma. All 3 reported cases thus far have proven to be
      benign lesions by pathological examination. Because clinical follow-up is
      reported only in the present case, caution should be exercised in declaring the
      solid serous adenoma of the pancreas as a benign lesion.

PMID- 16804416
TI  - Antioxidant treatment with taurine ameliorates chronic pancreatitis in an
      experimental rat model.
AB  - OBJECTIVES: Based on the results of recent studies that reported depleted
      antioxidant capacity in patients with chronic pancreatitis (CP), prevention of
      free radical production has gained importance in antifibrotic treatment
      strategies in CP. The aim of this study was to investigate the effects of taurine
      on oxidative capacity and fibrosis in experimental chronic rat pancreatic
      fibrosis. METHODS: CP was induced in male Sprague-Dawley rats by intraductal
      trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol. Taurine was given
      intraperitoneally at a concentration of 1000 mg/kg. The treatment groups were as
      follows: group 1, TNBS plus normal saline (NS); group 2, TNBS plus taurine; group
      3, ethanol plus NS; and group 4, NS plus NS. Each group contained 15 animals.
      Treatment was started after established CP. After 4 weeks of treatment, markers
      of oxidative stress and the degree of pancreatic fibrosis were determined.
      RESULTS: The amount of weight loss was significantly lower in the taurine-treated
      group with CP (P < 0.002). Tissue malondialdehyde levels increased and superoxide
      dismutase and glutathione peroxidase activities decreased significantly after
      treatment as well (P < 0.001). Histopathologic scores were also lower in taurine
      treated animals with CP (P < 0.005). CONCLUSIONS: Taurine treatment improved the
      degree of oxidative stress and fibrosis in rat CP. Antioxidant treatment might be
      considered a novel option to alleviate the fibrotic process in CP.

PMID- 16804418
TI  - Sweat chloride measurement with a highly sensitive electrode.

PMID- 16804420
TI  - An unusual solid pseudopapillary tumor of the pancreas.

PMID- 16804419
TI  - Hilar lymphadenopathy associated with autoimmune pancreatitis.

PMID- 16804421
TI  - Enhanced trypsin activity in pancreatic acinar cells deficient for serine
      protease inhibitor kazal type 3.

PMID- 16804422
TI  - Discussion on applicability of disseminated intravascular coagulation parameters
      in the assessment of the severity of acute pancreatitis.

PMID- 16804424
TI  - New rotavirus vaccines.

PMID- 16804425
TI  - The new pentavalent rotavirus vaccine composed of bovine (strain WC3) -human
      rotavirus reassortants.
AB  - BACKGROUND: Infantile gastroenteritis caused by human rotaviruses is a prevalent
      disease throughout the world, causing dehydration and hospitalization in all
      countries. In developing countries, it is associated with a high mortality. A
      licensed vaccine against rotavirus was withdrawn because of a causal association
      with intussusception. A new vaccine has been developed and is a candidate for
      licensure. METHODS: To recount the early development and recent demonstration of
      the safety and efficacy of the new vaccine. A bovine rotavirus attenuated for
      humans was isolated and reassorted with human rotaviruses of serotypes G1-4 and
      P1 to create a pentavalent vaccine. Multiple placebo-controlled clinical trials,
      including one involving approximately 70,000 infants, were conducted in multiple
      developed countries. RESULTS: The pentavalent vaccine was well tolerated by
      infants less than 8 months of age, and the incidence of intussusception was
      similar among vaccine and placebo recipients. More than 90% of infants had a
      significant rise in serum antirotavirus IgA titer after 3 doses. Efficacy of 95%
      against severe disease causing hospitalization or emergency care was
      demonstrated, and pentavalent vaccine prevented 74% of all rotavirus disease.
      CONCLUSIONS: If widely used, pentavalent vaccine would control rotavirus disease
      in the United States and other developed countries and could also have a major
      effect in developing countries.

PMID- 16804426
TI  - Impact of acute rotavirus gastroenteritis on pediatric outpatient practices in
      the United States.
AB  - OBJECTIVES: The objectives of this study were to determine the presenting
      symptoms, healthcare utilization, and lost time from work and day care associated
      with acute rotavirus gastroenteritis. METHODS: During the winter to spring
      seasons of 2002-2003 or 2003-2004, children <36 months of age presenting with
      acute gastroenteritis to urban and suburban pediatric outpatient practices
      affiliated with 5 academic centers across the United States were enrolled in
      similarly designed studies. The case definition required >or=3 watery or looser
      than-normal stools and/or forceful vomiting within a 24-hour period beginning
      <or=72 hours before presentation. Stool samples were tested for rotavirus antigen
      by standard commercial assays. Symptom frequencies for laboratory-confirmed
      rotavirus and nonrotavirus gastroenteritis were compared by Fisher's exact test;
      the number of healthcare contacts and lost days from work or day care were
      compared with the median 2-sample test. RESULTS: Stool specimens were obtained
      from 284 of 303 (94%) participants; 115 (40%) of tested specimens were positive
      for rotavirus (range, 31-50% across the 5 centers). Compared with participants
      with nonrotavirus gastroenteritis, children with rotavirus gastroenteritis were
      more likely to have 1) vomiting (83% versus 66%; P = 0.003), 2) combined diarrhea
      and vomiting (75% versus 50%; P < 0.001), and 3) fever (60% versus 43%; P =
      0.010). More time from work was lost by parents/guardians of children with
      rotavirus than nonrotavirus gastroenteritis (median 2 versus 0 day; P = 0.007).
      More day care was missed by children with rotavirus than nonrotavirus
      gastroenteritis (median 3 versus 1 day; P = 0.002). CONCLUSIONS: In this
      multicenter study, rotavirus consistently caused a sizable proportion of cases of
      acute gastroenteritis seen in pediatric outpatient practices in the United States
      during the winter and spring. Rotavirus gastroenteritis was more frequently
      associated with vomiting, combined diarrhea and vomiting, fever and lost time
      from work and day care than nonrotavirus gastroenteritis.

PMID- 16804427
TI  - A randomized, double-blind study of the safety, transmissibility and phenotypic
      and genotypic stability of cold-adapted influenza virus vaccine.
AB  - BACKGROUND: Live attenuated influenza vaccine (LAIV; FluMist) is a trivalent
      vaccine containing cold-adapted influenza vaccine viruses that infect and
      replicate in cells lining the nasopharynx to induce immunity. Recovery of viruses
      (shedding) is measured by culture of nasal specimens. Shedding of vaccine viruses
      is not equated with transmission because transmission requires more virus than is
      detected in many nasal swabs. Previous studies with LAIV did not detect
      transmission to close contacts. The primary objective of this study was to
      estimate the probability of transmission to placebo contacts in a day care
      setting. METHODS: One hundred ninety-seven healthy children aged 9 to 36 months
      attending day care were randomized to receive vaccine or placebo. Postvaccination
      viral shedding, safety, genotype and phenotype of shed viruses and probability of
      transmission were assessed. RESULTS: Eighty percent of 98 vaccine recipients shed
      at least one vaccine strain. No clinically significant differences in solicited
      adverse events attributable to vaccine occurred; safety profiles were similar in
      both groups. Vaccine virus isolates retained their phenotypic characteristics
      (cold adaptation and temperature sensitivity) and did not revert at nucleotides
      known to confer an attenuating phenotype. There was one confirmed transmission of
      a vaccine strain to a single placebo recipient. According to the Reed-Frost
      model, the calculated probability of transmission to a child after contact with a
      single vaccinated child was 0.58% (95% confidence interval, 0-1.7%). There was no
      increased reactogenicity or other safety concerns in the recipient child.
      CONCLUSIONS: Young children in a day care setting had a high rate of shedding and
      a low rate of transmission. No clinically significant illness occurred among
      children who received vaccine or placebo or in the child to whom the vaccine
      virus was transmitted.

PMID- 16804428
TI  - Influenza-related hospitalizations in children younger than three years of age.
AB  - BACKGROUND: To determine the rates of influenza-related hospitalization and to
      know the clinical manifestations and underlying diseases in children younger than
      3 years who are hospitalized with influenza. METHODS: Retrospective, descriptive
      study (1996-2003), performed in a tertiary teaching hospital in Madrid. Data of
      hospitalized children, younger than 3 years, with influenza virus isolation from
      nasal aspirates were collected. Rates of hospitalization for every year were
      calculated. RESULTS: Overall, 146 children hospitalized with influenza were
      identified: 117 had community-acquired influenza as the only disease, 18 had
      community-acquired influenza and were coinfected with other pathogens, and 11 had
      nosocomial infection. Rates of influenza hospitalization for years 1996, 1997,
      1998, 1999, 2000, 2001, 2002, and 2003 were 0.42, 0.11, 1.46, 1.54, 0.53, 0.25,
      0.19, and 0.82, respectively, per 1000 children younger than 3 years of age.
      Children <or=1 year of age accounted for almost two thirds of admissions.
      Bronchitis/bronchiolitis (42 children), pneumonia (11 children), fever without
      source (36 children), and suspected sepsis (9 children) accounted for almost 90%
      of all hospitalizations in children with community-acquired influenza.Forty-seven
      patients (40%) had underlying diseases, mainly chronic pulmonary disease and
      congenital heart disease. Ten patients (8.5%) with community-acquired influenza A
      and underlying conditions were admitted to the intensive care unit. CONCLUSIONS:
      Influenza is an important cause of hospitalization in young children. The use of
      influenza vaccine in high-risk children could prevent hospitalizations and cases
      of influenza-related diseases.

PMID- 16804429
TI  - Site-specific disease potential of individual Streptococcus pneumoniae serotypes
      in pediatric invasive disease, acute otitis media and acute conjunctivitis.
AB  - BACKGROUND: Recent studies have shown that some Streptococcus pneumoniae
      serotypes possess a higher potential to cause invasive disease than others.
      However, it is unknown whether disease potential for specific serotypes is
      similar for mucosal disease. Our objective was to assess the disease potential of
      individual S. pneumoniae serotypes causing invasive pneumococcal disease (IPD),
      acute otitis media (AOM) and acute conjunctivitis (AC) in children. METHODS:
      Serotypes of pneumococcal isolates from children with IPD, AOM and AC were
      compared with those carried by healthy children aged <3 years. All children
      resided in the same area and were studied during the same period. Odds ratios for
      disease were calculated for each diagnosis following multivariate analysis,
      including gender, age, ethnic group, previous antibiotic treatment and year
      variability. RESULTS: A total of 5,500 isolates were collected: 189 from blood or
      cerebrospinal fluid, 3,200 from middle ear fluid, 348 from conjunctiva and 1,763
      from nasopharynx of healthy children. A significant positive association with IPD
      was demonstrated for serotypes 1, 5 and 12F; with AOM for serotypes 1, 3, 5, 12F,
      19A and 19F; and with AC for serotype 3 and nontypeable S. pneumoniae. A
      significant negative association with IPD was demonstrated for nontypeable S.
      pneumoniae and with AOM for serotypes 6A, 6B, 15A and nontypeable S. pneumoniae.
      CONCLUSIONS: Our results reflect the importance of the polysaccharide capsule in
      site-specific disease potential and provide useful information regarding disease
      potential of nonvaccine serotypes shown to be involved in carriage replacement
      after vaccination with the 7-valent conjugate vaccine.

PMID- 16804431
TI  - Blood culture contamination in pediatric patients: young children and young
      doctors.
AB  - OBJECTIVE: The objective of this study was to assess the role played by the
      patient's age and physician's experience in determining the contamination rate of
      pediatric blood cultures. METHODS: The proportion of true-positive (isolation of
      a pathogen) and false-positive (isolation of a contaminant) results among blood
      cultures obtained by in-training physicians and experienced pediatricians from
      young children (aged 1-35 months) and older children (>or=36 months of age) and
      the value of a positive blood culture to predict a true-positive result were
      retrospectively determined. RESULTS: The odds of a positive blood culture to
      predict isolation of a true-pathogen was 0.366 only when the sample was obtained
      by an inexperienced physician and 0.523 when it was drawn by an experienced
      physician (P < 0.001), 0.419 when it was obtained from a young child and 0.429
      when it was drawn from an older child (P = 0.781). The predictive value of a
      positive result for isolating a pathogen was significant higher when an
      experienced physician drew the blood culture regardless of the patient's age.
      CONCLUSIONS: Patient's young age and lack of experience of the physician who
      draws the specimen increase the risk of blood culture contamination. These
      results strengthen the need to improve the technical skills of young physicians.

PMID- 16804430
TI  - T-antigen activation for prediction of pneumococcus-induced hemolytic uremic
      syndrome and hemolytic anemia.
AB  - BACKGROUND: Among the most severe complications of invasive pneumococcal
      infection are hemolytic uremic syndrome (P-HUS) and hemolytic anemia (P-HA),
      which occur when the Thomsen-Freidenreich antigen (TA) is exposed on
      erythrocytes, platelets and glomeruli. METHODS: To determine the positive
      predictive value, sensitivity, and specificity of early TA activation testing for
      P-HUS or P-HA and to compare the microbiologic features of pneumococcus isolates
      associated or not associated with TA activation. The case records for 36 patients
      with invasive pneumococcal infection who had been tested for TA activation were
      retrospectively reviewed. Clinical and laboratory data were compared between
      patients with and without TA activation. RESULTS: Positive TA activation was 86%
      sensitive and 57% specific for P-HUS or P-HA. The positive predictive value was
      76%. There were no between-group differences in antibiotic susceptibility of the
      pneumococcal isolates. Pneumococcal serotype 14 was the most frequent (5/10
      isolates tested) serotype causing P-HUS. Of the 36 patients, 13 required packed
      red blood cell transfusion, 3 died, and 2 required extracorporeal membrane
      oxygenation. No patient had long-term renal sequelae. CONCLUSIONS: TA activation
      is a reasonable predictor of P-HUS or P-HA and could be useful if tested soon
      after invasive pneumococcal disease is first diagnosed.

PMID- 16804432
TI  - The safety and immunogenicity of a quadrivalent measles, mumps, rubella and
      varicella vaccine in healthy children: a study of manufacturing consistency and
      persistence of antibody.
AB  - BACKGROUND: This clinical trial was conducted to demonstrate that each of 3
      consistency lots of a combined measles, mumps, rubella and varicella vaccine
      (MMRV) would be well tolerated, induce clinically acceptable and similar immune
      responses to each antigen and induce immune responses similar to measles, mumps
      and rubella vaccine (MMR) administered concomitantly with varicella vaccine (V).
      An additional objective was to evaluate the persistence of antibodies 1 year
      postvaccination. METHODS: Study participants 12 to 23 months of age received a
      single injection of either one of 3 consistency lots of MMRV or MMR + V
      administered at separate injection sites. RESULTS: A total of 3,928 healthy
      children were enrolled at study sites in the United States and Canada. Immune
      responses to measles, mumps, rubella and varicella in children immunized with
      each of 3 lots of MMRV were similar and the combined response to all 3 lots was
      comparable to that of the control group. The 1-year antibody persistence rates
      for measles, mumps, rubella and varicella viruses were each greater than 95% and
      comparable among the recipients of the 3 consistency lots of MMRV and the control
      group. All vaccines were generally well tolerated during the 42 days after
      vaccination and the overall incidence of adverse experiences was comparable
      between recipients of MMRV and MMR + V. Rates of fever (temperature >or=38.9
      degrees C oral equivalent or tactile) were greater in recipients of MMRV than in
      recipients of MMR + V (39.1% versus 33.1%, P = 0.001). Fevers were transient and
      there was no difference in the incidence of febrile seizures. CONCLUSIONS: MMRV
      was generally well tolerated and had comparable immunogenicity and overall safety
      profiles to MMR + V administered concomitantly. Long-term persistence of
      antibodies after receipt of MMRV is expected based on similar antibody titers
      against all 4 antigens 1 year postvaccination compared with recipients of MMR and
      V.

PMID- 16804433
TI  - Observational cohort study of HIV-infected African children.
AB  - BACKGROUND: Most information about children living with HIV is based on follow up
      from children identified through mother-to-child transmission studies. Children
      identified through voluntary counseling and testing (VCT) represent a unique
      cohort that has not been previously described in the literature. METHODS:
      Children who were found to have HIV infection through VCT were offered enrollment
      in this study. They were evaluated monthly and encouraged to return to the clinic
      any time they were ill. Thorough evaluation was performed for every illness.
      RESULTS: Forty-five children were enrolled in the study. Many of the participants
      (33%) had a serious acute disease at the time of enrollment. The most common
      diagnoses were symptomatic malaria and pneumonia. The children were more ill than
      adults who were enrolled in a simultaneous study and had a higher death rate (37
      versus 15 deaths per 100 person-years of observation). The mortality rate was
      22%. Undernutrition and low CD4 cell count were independently associated with
      increased risk of death. CONCLUSIONS: Malawian children found to be HIV-infected
      through VCT had a high morbidity and mortality rate, highlighting the potential
      benefit of trimethoprim-sulfamethizole prophylaxis and available antiretroviral
      therapy.

PMID- 16804434
TI  - Hospitalization trends among children and youths with perinatal human
      immunodeficiency virus infection, 1990-2002.
AB  - BACKGROUND: Major improvements in disease progression among HIV-infected children
      have followed the adoption of combination antiretroviral therapy. METHODS: We
      examined trends in hospitalization rates between 1990-2002 among 3,927
      children/youths with perinatal HIV infection, ranging in age from newborn to 21
      years. We used Poisson regression to test for trends in hospitalization rates by
      age and year; binomial regression to test for trends in intensive care unit (ICU)
      admissions and hospitalization at least once and more than once, by age and year;
      and multivariate logistic regression to examine factors associated with
      hospitalization, ICU admission, and hospitalization longer than 10 days. RESULTS:
      Statistically significant downward trends in hospitalization rates and multiple
      hospitalizations were observed in all age groups from 1990-2002. The proportion
      of HIV-infected children/youths who were hospitalized at least once declined from
      30.4% in 1990 to 12.9% in 2002, with a steady decline occurring after 1996, when
      the U.S. Public Health Service issued guidelines recommending triple-drug
      antiretroviral therapy (triple therapy) for HIV-infected children. ICU admissions
      declined significantly in all age groups except among children younger than 2
      years. Logistic regression results indicated that black and Hispanic
      children/youths were significantly more likely to be hospitalized than white
      children/youths and that children/youths receiving triple therapy were
      significantly more likely to be hospitalized than therapy-naive children; the
      latter association was not observed among children monitored from 1997-2002.
      CONCLUSIONS: Substantial reductions in rates of hospitalization, multiple
      hospitalizations, and ICU admission have occurred among HIV-infected
      children/youths from 1990-2002, particularly after 1996, with increased use of
      triple therapy.

PMID- 16804436
TI  - Intravenous immunoglobulin: production, uses and side effects.

PMID- 16804435
TI  - Fungal infections in children with cancer: a prospective, multicenter
      surveillance study.
AB  - BACKGROUND: Data on epidemiology and survival after fungal infections in patients
      with cancer are primarily based on studies in adults, whereas few data are
      available on children. METHODS: A prospective, multicenter, 2-year surveillance
      of fungal infections in children receiving antineoplastic treatment was performed
      in 15 Italian centers. For each case, defined by means of EORTC-IFIG/NIAID-MSG,
      information was collected on age, phase of treatment, presence of neutropenia or
      lymphocytopenia, administration of antifungal drugs and survival. RESULTS: Ninety
      six episodes (42 proven [19 fungemias, 23 deep tissue infections], 17 probable
      and 37 possible invasive mycoses) were reported. Most of them (73%) followed
      aggressive chemotherapy, 21% allogeneic hematopoietic stem cell transplantation
      and only 6% moderately aggressive treatment. Neutropenia was present in 77% of
      the episodes, and it had a longer duration before deep tissue mycosis as compared
      with fungemia (P = 0.020). Lymphocytopenia was present in 75% of the episodes
      observed in nonneutropenic patients. As compared with children with fungemia,
      patients with probable invasive mycoses had a 25.7-fold increased risk of death,
      whereas it was 7.7-fold greater in children with possible invasive mycoses and 5
      fold higher in those with proven deep tissue infection (P = 0.004). The risk of
      death was also 3.8-fold higher in patients already receiving antifungals at the
      time of diagnosis of infection as compared with those not receiving antimycotic
      drugs. CONCLUSIONS: In children with cancer, aggressive antineoplastic treatment,
      severe and longlasting neutropenia and lymphocytopenia are associated with fungal
      infections. These features as the clinical pictures are similar to those reported
      in adults, but in children, the overall and the infection-specific (fungemia or
      mycosis with deep tissue infection) mortalities are lower.

PMID- 16804437
TI  - Systemic antifungal therapy for cutaneous infections in children.

PMID- 16804439
TI  - Immune reconstitution syndrome precipitated by bacille Calmette Guerin after
      initiation of antiretroviral therapy.
AB  - Immune reconstitution syndrome resulting from bacille Calmette Guerin (BCG)
      vaccine occurring 2 weeks to 2 months after institution of antiretroviral therapy
      (ART) in children has been well documented. We report the earliest onset of BCG
      related immune reconstitution syndrome developing 1 week after initiation of ART.

PMID- 16804438
TI  - Immune reconstitution syndrome from nontuberculous mycobacterial infection after
      initiation of antiretroviral therapy in children with HIV infection.
AB  - The immune reconstitution syndrome caused by nontuberculous mycobacterial (NTM)
      infection is reported in 9 of 153 HIV-infected children 2 to 26 weeks after
      initiation of antiretroviral therapy. The clinical syndrome included fever and
      dyspnea (2 children), fever and abdominal pain (3), subcutaneous nodules or
      suppurative lymphadenitis (4). The causative species were Mycobacterium avium
      (4), Mycobacterium scrofulaceum (3), Mycobacterium kansasii (1) and Mycobacterium
      simiae (1).

PMID- 16804440
TI  - Severe airway obstruction in a child with Pott's disease.
AB  - Airway obstruction associated with Pott's disease is rare. We present a case of
      severe airway obstruction caused by an extensive paravertebral mediastinal
      abscess in a 3-year-old boy with tuberculosis of the thoracic spine.

PMID- 16804441
TI  - Norovirus-associated encephalopathy.
AB  - Norovirus is a common cause of gastroenteritis. We describe the case of a 23
      month-old girl with encephalopathy possibly associated with norovirus infection.
      The viral genome was detected in stool, serum and cerebrospinal fluid (CSF) by
      reverse transcription polymerase chain reaction. This is the first report of
      encephalopathy potentially caused by norovirus as indicated by the presence of
      the virus genome in CSF.

PMID- 16804443
TI  - Molecular evidence of congenital candidiasis associated with maternal candidal
      vaginitis.
AB  - A premature newborn born to a mother with candidal vaginitis developed congenital
      invasive candidiasis. The isolates of Candida albicans from the bloodstream and
      the oral cavity of the neonate and the vagina of the mother shared a common
      genotype, which provide direct evidence of the association of congenital
      candidiasis with candidal vaginitis in the mother.

PMID- 16804442
TI  - Persistent Staphylococcus capitis septicemia in a preterm infant.
AB  - A preterm infant had persistent Staphylococcus capitis septicemia with 11
      consecutive positive blood cultures over a period of 33 days. The clinical
      evidence suggested that the source of infection probably originated from the
      gastrointestinal tract. The combination of rifampin and linezolid treatment,
      together with prolonged stoppage of enteral feeding, successfully terminated the
      infection. Rifampin and linezolid should be considered as alternative
      antimicrobial agents when glycopeptides fail to eradicate Gram-positive pathogens
      from the host.

PMID- 16804444
TI  - Disseminated blastomycosis in an infant.
AB  - Blastomycosis is an uncommon life-threatening disease caused by the dimorphic
      fungus Blastomyces dermatitidis. Estimates of the percentage of cases occurring
      in children range from 2% to 11%, and it is exceedingly rare in individuals less
      than 1 year of age. We present the case of an otherwise healthy infant with
      disseminated blastomycosis acquired in Northern Ontario and a brief review of the
      pediatric literature.

PMID- 16804445
TI  - Majocchi's granuloma in a 3-year-old boy.
AB  - A 3-year-old boy presented with a 15 x 15-cm papulonodular lesion on his left
      shin of 8 weeks' duration. The lesion was considered a Majocchi's granuloma
      caused by Trichophyton tonsurans. He was treated with griseofulvin and topical
      clotrimazole and hydrocortisone cream and responded well after 8 weeks of
      treatment.

PMID- 16804446
TI  - Fatal group A streptococcal myopericarditis during influenza A infection.
AB  - Influenza A infection can be a serious and life-threatening disease in young
      children. Even in those who die, however, the cause of death may not be obvious.
      In this illustrative report, a 7-year-old child with acute influenza A infection
      developed an unsuspected fatal secondary infection caused by group A
      streptococcus. The diagnosis of bacterial myopericarditis was made at autopsy.

PMID- 16804448
TI  - Human coronavirus nomenclature.

PMID- 16804449
TI  - Tuberculosis of rib and lung presenting as subcutaneous emphysema.

PMID- 16804450
TI  - Nasal continuous positive airway pressure and gram-negative sepsis in low
      birthweight infants.

PMID- 16804451
TI  - Reply.

PMID- 16804452
TI  - Consensus statement on surgery journal authorship--2006.

PMID- 16804453
TI  - Quality of life after laparoscopic gastric banding: Prospective study (152 cases)
      with a follow-up of 2 years.
AB  - To evaluate influence of laparoscopic gastric banding (LGB) on quality of life
      (QOL) in patients with morbid obesity. Laparoscopic adjustable gastric banding is
      a popular bariatric operation in Europe. The objectives of surgical therapy in
      patients with morbid obesity are reduction of body weight, and a positive
      influence on the obesity-related comorbidity as well the concomitant psychologic
      and social restrictions of these patients. In a prospective clinical trial,
      development of the individual patient QOL was analyzed, after LGB in patients
      with morbid obesity. From October 1999 to January 2001, 152 patients [119 women,
      33 men, mean age 38.4 y (range 24 to 62), mean body mass index 44.3 (range 38 to
      63)] underwent evaluation for LGB according the following protocol: history of
      obesity; concise counseling of patients and relative on nonsurgical treatment
      alternatives, risk of surgery, psychologic testing, questionnaire for eating
      habits, necessity of lifestyle change after surgery; medical evaluation including
      endocrinologic and nutritionist work-up, upper GI endoscopy, evaluation of QOL
      using the Gastro Intestinal Quality of Life Index (GIQLI). Decision for surgery
      was a multidisciplinary consensus. This group was follow-up at least 2 years,
      focusing on weight loss and QOL. Mean operative time was 82 minutes; mean
      hospital stay was 2.3 days and the mean follow-up period was 34 months. The BMI
      dropped from 44.3 to 29.6 kg/m and all comorbid conditions improved markedly:
      diabetes melitus resolved in 71% of the patients, hypertension in 33%, and sleep
      apnea in 90%. However, 26 patients (17%) had late complications requiring
      reoperation. Preoperative global GIQLI score was 95 (range 56 to 140),
      significant different of the healthy volunteers score (120) (70 to 140) P <
      0.001. Correlated with weight loss (percentage loss of overweight and BMI), the
      global score of the group increased to 100 at 3 months, 104 at 6, 111 at 1 year
      to reach 119 at 2 years which is no significant different of healthy patients.
      Analyzing the subscale, physical condition, emotional status, and social
      integration increased significantly (P < 0.001) from preoperative to end of
      follow-up. Digestive symptoms were not modified. In case of failure of the
      procedure (10.5%) global Giqli score is not modified. Patients who have required
      successful revisional surgery for late complications (6.5%) have an excellent QOL
      outcome that are not different from the whole group. Together with a satisfactory
      reduction of the excess overweight, laparoscopic gastric banding may lead in a
      carefully selected population of patients with morbid obesity to a significant
      improvement of patient QOL, in at least 2 years follow-up.

PMID- 16804454
TI  - Safety of argon plasma coagulation for hemostasis during endoscopic mucosal
      resection.
AB  - Showing the safety of argon plasma coagulation (APC) over mucosal defects
      during/after endoscopic mucosal resection (EMR), 2 studies using resected pig (ex
      vivo) and living minipig (in vivo) stomachs were performed. As an ex vivo study,
      APC was applied over mucosal defects in 2 groups; with prior submucosal saline
      injection and without injection. Only subtle tissue damage was observed in the
      injection group, whereas apparent damage was observed in the noninjection group.
      The damaged distances in depth significantly increased as the pulse duration
      increased and those at the pulse duration of 4 seconds, which might be maximal in
      clinical practice, were approximately 1 mm. As an in vivo study, APC was applied
      over mucosal defects immediately after EMR. Only subtle tissue damage was
      observed even at the pulse duration of 20 seconds as shown in the ex vivo study.
      APC can be performed safely over the mucosal defects during/after EMR.

PMID- 16804455
TI  - Laparoscopic adrenalectomy: Comparison of lateral transperitoneal and lateral
      retroperitoneal approaches.
AB  - Laparoscopic adrenalectomy has become the method of choice of removal of most of
      adrenal lesions. This study investigated and compared the results of 2 different
      approaches of laparoscopic adrenalectomy, through retrospective review of 40
      patients. Within this study period between 1995 and 2004, there were 20 lateral
      retroperitoneal and 20 lateral transperitoneal laparoscopic adrenalectomies
      performed. There was no significant difference in demographic variables between
      the 2 groups. Operative time, days to diet and ambulation, hospital stay, rate of
      conversion and complication did not differ significantly between the 2
      approaches. No recurrence was detected upon mean follow-up period of 15.9 months.
      Learning curves showed gradual decrease in operation time in both approaches,
      reflecting maturation of techniques. In conclusion, both lateral transperitoneal
      and lateral retroperitoneal laparoscopic adrenalectomy are safe and effective.
      There is no difference in outcome between 2 approaches.

PMID- 16804456
TI  - A prospective, randomized controlled trial comparing n-butyl cyanoacrylate tissue
      adhesive (LiquiBand) with sutures for skin closure after laparoscopic general
      surgical procedures.
AB  - The aim of this study was to compare the efficacy of n-butyl-cyanoacrylate tissue
      adhesive (Liquiband) with nonabsorbable monofilament sutures for laparoscopic
      port site closure. Adult patients having elective laparoscopic procedures were
      randomly allocated to wound closure with sutures or tissue adhesive. End points
      included skin closure time, wound dressing requirements, wound complications, and
      cosmesis, assessed at discharge, 4 to 6 weeks and 3 months. Seventy-eight
      patients randomized to receive sutures and 76 to receive tissue adhesive were
      eligible for final analysis. Mean closure time was significantly longer for
      sutures (220 vs. 125 s, P < 0.001). Fewer dressings were required in the tissue
      adhesive group immediately postoperatively (21% vs. 97%, P < 0.001) and at
      discharge (24% vs. 82%, P < 0.001). There were no significant differences in
      wound complications or in cosmesis at either 4 to 6 weeks or at 3 months. Tissue
      adhesive for laparoscopic port site closure offers potential savings with respect
      to time and has comparable wound complication rates and cosmetic outcomes when
      compared with nonabsorbable monofilament sutures.

PMID- 16804457
TI  - What we learned from the experience of laparoscopic splenectomy in patients with
      idiopathic thrombocytopenic purpura (ITP)--single surgeon experiences.
AB  - From October 1994 to December 2004, 50 cases of laparoscopic splenectomy (LS)
      have been carried out by a single surgeon for treating patients with idiopathic
      thrombocytopenic purpura (ITP). This study was performed to analyze a single
      surgeon's experiences of LS in ITP and discuss lesions that we have learned and
      the technical changes based on perioperative outcomes of LS. It seems that strict
      right lateral decubitus is definitively the position of choice because it ensures
      good exposure of splenic vascular structure in hilum. We also found that a
      flexible scope or 45-degree angled telescope, not to mention a 30-degree one,
      allowed for optimal vision, and made laparoscopic procedures easy and secure. We
      could control the vascular structure safely by just applying 5-mm laparoscopic
      clips without using harmonic scalpel or endo-GIA. When delivering spleen, it
      maybe easy and safe way to remove the plastic pouch with spleen fragmented
      through the umbilical port after changing the patient's position to supine again.

PMID- 16804458
TI  - Closed blunt-trocar 5 mm-port for primary cannulation in laparoscopic surgery: A
      safe technique.
AB  - Primary cannulation of the peritoneal cavity is a critical part of laparoscopic
      surgery. The aim of this study was to evaluate the safety and applicability of a
      direct blunt-port primary cannulation. The peritoneal cavity was accessed by
      direct trocar-port insertion at sites other than the umbilicus and avoiding
      abdominal scars. A 5-mm port with a smooth blunt tip conical trocar was employed
      using a closed technique. The closed blunt trocar-port technique for primary
      cannulation of the peritoneal cavity was applied in 503 of 524 patients (96%) who
      underwent laparoscopic surgery between 2002 and 2005. Some 199 patients (38%) had
      abdominal scars of previous surgery. There were no major complications, but minor
      complications occurred in 3 patients (0.6%). No bowel or retroperitoneal vascular
      injuries were encountered. The closed introduction of a blunt-tipped 5-mm port,
      conical-trocar is a simple technique for primary cannulation in laparoscopic
      surgery that allows safe and rapid access to the peritoneal.

PMID- 16804460
TI  - Gastro cutaneous fistula after laparoscopic cholecystectomy: A case report.
AB  - A young lady presented with a nonhealing epigastric sinus after 2 years of
      laparoscopic cholecystectomy performed outside. Upper gastrointestinal (GI)
      endoscopy and contrast study confirmed its communication with the stomach. At
      relaparoscopy, the fistula was identified, dissected, and stapled with endo-GIA
      stapler. Patient made an uneventful postoperative recovery and she is well after
      20 months of surgery. It may be concluded that laparoscopic cholecystectomy can
      lead to the development of gastrocutaneous fistula that can be managed by
      relaparoscopy and stapling the tract with endo-GIA devices.

PMID- 16804459
TI  - Achalasia after vertical banded gastroplasty for morbid obesity: A case report.
AB  - Achalasia is an unusual motility disorder that can be seen in conjunction with
      obesity. The prevalence of achalasia is unknown in obese patients and when
      present, the clinical characteristics are atypical. We report a case of achalasia
      that was diagnosed 13 years after a vertical-banded gastroplasty was performed.

PMID- 16804462
TI  - Laparoscopic cholecystectomy for acute cholecystitis in patient with situs
      viscerum inversus.
AB  - Situs viscerum inversus is a rare condition with perfect mirror image organs
      position. Despite the well-described existence of this condition, the implication
      for the treating of emergency pathology can be important following to the
      difficult interpretation of signs and symptoms. We report a case of acute
      cholecystitis in patients with known dextrocardia who was successfully treated by
      laparoscopic cholecystectomy. The diagnostic problems and surgical technique
      pitfalls are discussed.

PMID- 16804461
TI  - Complications of retained intraperitoneal gallstones from laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy is now the gold standard procedure for the treatment
      of symptomatic gall bladder stones. Spillage of gall bladder stones into the
      peritoneal cavity may occur due to inadvertent iatrogenic gall bladder
      perforation during dissection of the gall bladder. We report a case of a 66 year
      old woman who had to return to theatre three times over two years to deal with
      complications from retained intra-peritoneal gallstones that were spilt at her
      initial laparoscopic cholecystecomy.

PMID- 16804463
TI  - Unexpected adhesions to a previously inserted preperitoneal mesh plug.
AB  - Adhesion formation is a long-term complication of laparoscopic inguinal hernia
      surgery-particularly by the transabdominal preperitoneal technique; but it is not
      thought to occur after open repair. We describe a gentleman presenting with a
      recurrent hernia who had previously undergone an open mesh plug repair 4 years
      earlier. At laparoscopy he was found to have considerable adhesions associated
      with the plug. These were successfully divided before repair. This case
      illustrates the possibility of intra-abdominal adhesions developing even after
      open hernia surgery.

PMID- 16804464
TI  - Laparoscopic repair of Morgagni hernia.
AB  - BACKGROUND: Morgagni hernia is a rare type of diaphragmatic hernia which
      represents less than 5% of all congenital diaphragmatic hernias. Patients are
      generally asymptomatic and are diagnosed incidentally. When symptomatic, it
      generates symptoms due to the compression of thoracic organs or compression of
      herniated intraabdominal organs. Once diagnosed, the condition requires prompt
      surgical correction. The defect is repaired either by primary suture or by the
      use of a prosthetic mesh. In adults, prosthetic mesh repair is preferred.
      Recently, laparoscopic repair of Morgagni hernia has been introduced and gained
      wide acceptance. MATERIALS AND METHODS: Between 2002 and 2004, 5 patients with
      Morgagni hernia were treated laparoscopically at our department. Female/male
      ratio was 3/2. Mean age was 56 years (range 41 to 69 y). Diagnosis were made by
      chest x-ray and CT scan. Herniation was on the left in 2 patients, and on the
      right in 3. The content of hernial sac was transverse colon and stomach. There
      were 2 separate defects in a patient with left-sided hernia. All cases were
      laparoscopically treated using prosthetic material. RESULTS: All operations were
      completed laparoscopically. The postoperative hospital stay was 3 to 5 days with
      a mean of 4 days. None of the patients developed any complication in the early
      postoperative period. The mean follow-up period is 7 months (range 3 to 24 mo).
      All patients are actually in good health and without recurrence. CONCLUSION:
      Laparoscopic repair of Morgagni hernia is a safe, simple, and reliable procedure
      which presents all the advantages of the minimally invasive surgery.

PMID- 16804465
TI  - Preoperative application of selective angiographic embolization in the treatment
      of focal nodular hyperplasia.
AB  - A focal nodular hyperplasia (FNH) rarely requires surgical intervention unless
      complications or clinical symptoms come into play. In 2 female patients, ages 35
      and 44, with symptomatic tumors of that entity (10 and 14 cm, respectively, in
      size) we performed a laparoscopic liver resection. Directly before undergoing
      this operation they underwent a selective angiographic embolization of the
      arterial inflow for control of hemorrhage by application of polyvinyl alcohol
      particles to the afferent arteries. This procedure led to a complete interruption
      in arterial inflow and the subsequent laparoscopic resection itself could be
      carried out as planned with minimal blood loss as well an uncomplicated
      postoperative course. The patients demonstrated a high degree of subjective
      satisfaction with the procedure. A reduction in arterial inflow through selective
      embolization is a useful tool in the preparation for laparoscopic resection of
      large, well-vascularized liver tumors.

PMID- 16804466
TI  - Laparoscopic splenectomy in patients with inflammatory pseudotumor of the spleen:
      Report of 2 cases and review of the literature.
AB  - We report 2 cases of splenic inflammatory pseudotumor treated by laparoscopic
      splenectomy. The first patient was a 58-year-old woman who complained of
      constipation. Computed tomography (CT) showed a well-demarcated mass that
      measured 4 cm in diameter and was not enhanced. She underwent laparoscopic
      splenectomy under a preoperative diagnosis of hemangioma. The final
      histopathologic diagnosis was inflammatory pseudotumor. The second patient was a
      29-year-old man who complained of abdominal pain. Computed tomography revealed a
      demarcated splenic tumor that measured 3 cm in diameter and was not enhanced.
      Laparoscopic splenectomy was performed. The pathologic and operative diagnoses
      were both inflammatory pseudotumor. In both cases, the postoperative course was
      uneventful, and the postoperative hospital stays were 10 and 11 days.
      Preoperative diagnosis of a splenic inflammatory pseudotumor is very difficult.
      However, laparoscopic splenectomy is safe and beneficial treatment for this tumor
      and should be performed in cases in which it is diagnosed.

PMID- 16804467
TI  - Minimally invasive surgery in the treatment of splenosis.
AB  - Splenosis has been serious etiologic reason in the recurrence of benign
      hematologic diseases after elective open or laparoscopic splenectomy. Although,
      the incidence of splenosis in patients splenectomized for trauma is high, as long
      as they are asymptomatic, they do not require surgical treatment. Herein, we
      report a case of idiopathic thrombocytopenic purpura recurrence due to splenosis
      5 years after the initial laparoscopic splenectomy. Laparoscopic treatment of
      splenosis was performed successfully.

PMID- 16804468
TI  - Nonelevation of serum CA 19-9 level in a true nonparasitic splenic cyst.
AB  - The diagnosis and management of true nonparasitic splenic cysts has markedly
      changed in recent years. The use of serum CA 19-9 has been increasingly advocated
      for diagnosis, while the advent of minimally invasive surgery has radically
      altered surgical management. We present the first case of a true nonparasitic
      splenic cyst in which serum CA 19-9 was not elevated. Treatment was by
      laparoscopic cyst decapsulation utilising the endoscopic Ligasure.

PMID- 16804469
TI  - Laparoscopic splenectomy in an adipose elderly patient with symptomatic non
      Hodgkin lymphoma-related splenomegaly and traumatic central splenic hematoma.
AB  - During recent years, laparoscopic splenectomy has shown to be a safe and
      effective surgical approach in patients with hematologic disorders requiring
      spleen removal. Especially in cases with splenomegaly, the laparoscopic approach
      results in a shorter hospital stay and faster recovery of the patients. Due to
      the increasing experience in laparoscopy, this approach also is emerging to be a
      therapeutic option in patients with blunt abdominal trauma with splenic rupture
      or hematoma. We report the case of an 80-year-old female patient who underwent
      laparoscopic splenectomy for symptomatic splenomegaly due to non-hodgkin Lymphoma
      in combination with stable traumatic splenic hematoma after blunt abdominal
      trauma.

PMID- 16804471
TI  - Re: Massive subcutaneous emphysema after thoracoscopic argon beamer use for
      pleurodesis. Surg lap endosc percut tech. 2005;15(4):252-255.

PMID- 16804472
TI  - Re: Radiofrequency ablation for hyperparathyroidism: Can it be a new treatment?
      Surg Lap Endosc Percut Tech. 2006;16(2):116.

PMID- 16804473
TI  - An overview of methods for calculating the burden of disease due to specific risk
      factors.
AB  - There are a number of measures that quantify the public health burden due to
      specific risk factors for specific diseases. Although these measures are of
      importance for policymakers, epidemiologists do not often calculate them or may
      be unfamiliar with some of the issues involved when they do. The primary measure
      of interest is the attributable fraction (AF), representing the fraction of cases
      or deaths from a specific disease that would not have occurred in the absence of
      exposure to a specific risk factor either in the exposed population or the
      population as a whole. AFs can be multiplied by the total number of cases of a
      given disease to obtain a "body count"--the absolute number of preventable cases
      due to a specific risk factor. Two other measures of public health burden, used
      in conjunction with AFs, are attributable years-of-life-lost and attributable
      disability-adjusted life-years. We provide an overview of the AF and related
      measures and discuss some of the specific issues involved in calculating AFs.
      These issues include calculating the variance of AFs (such as Monte Carlo
      sensitivity methods), biases arising from some formulas for the AF, sources of
      data for calculating AFs, dependence of AFs on basic decisions about what
      exposure-disease associations are causal, and extrapolation from the source
      population to the target population.

PMID- 16804474
TI  - Breast cancer trends among young women in the United States.
AB  - BACKGROUND: It has been suggested that exposures associated with
      industrialization have increased breast cancer risk among young women in recent
      decades in the United States despite data demonstrating declining breast cancer
      mortality in birth cohorts born after 1945. METHODS: Trends for in situ and
      invasive breast cancer incidence rates from 1975 through 2002 among white and
      black U.S. women ages 20 to 49 are evaluated by decade of age using linear
      regression analyses. RESULTS: Despite increasing rates of in situ breast cancer
      after 1980 reflecting increased use of mammography, invasive breast cancer rates
      declined for both white and black women under age 50. These declines are
      consistent with a decrease in birth cohort risk of breast cancer for women born
      after 1945. CONCLUSIONS: Invasive breast cancer incidence rates are not
      increasing in young U.S. women despite increases in mammography and trends in
      known risk factors (eg, reproductive factors) that would predict increasing risk.

PMID- 16804475
TI  - Still protected against smallpox? Estimation of the duration of vaccine-induced
      immunity against smallpox.
AB  - BACKGROUND: Although the potential for bioterrorism has led to discussions on the
      durability of vaccine-induced immunity, the actual duration of protection against
      smallpox is still unknown. It has previously been suggested that at least partial
      protection against severe and fatal smallpox may persist throughout life.
      METHODS: In this article, we analyzed 6 major smallpox outbreaks that occurred
      before and after 1900 in the United Kingdom. These analyses are based on the age
      dependent incidence of smallpox and the fraction of severe manifestations among
      individuals with or without prior vaccination. We used a likelihood-based
      approach to estimate the duration of immunity from the age-specific frequencies.
      RESULTS: The expected median duration of protection from disease ranged from 11.7
      to 28.4 years after primary vaccination, and the qualitative pattern of duration
      could be described using Gompertz's Law. Vaccinated individuals appear to have
      been protected from severe disease with more than 50% probability even 50 years
      after successful primary vaccination. CONCLUSIONS: These findings suggest that
      successful primary vaccination offered full protection for a few decades, with
      partial protection from severe smallpox possibly lasting a lifetime, for a
      substantial fraction of the population.

PMID- 16804476
TI  - [Fractures of the condylar region: functional treatment or surgery?].

PMID- 16804477
TI  - [Diversity and versatility: obstacles to excellence?].

PMID- 16804478
TI  - [Dental implants in irradiated areas: a series of 33 patients].
AB  - INTRODUCTION: Prosthetic rehabilitation, particularly in radiated areas, can be
      particularly difficult in patients with partial or total edentation following
      treatment for orofacial cancer. We report a series of patients who underwent a
      protocol of implantation in radiated bone with evaluation of the prosthetic
      rehabilitation. MATERIAL AND METHOD: Thirty-three patients given radiotherapy for
      an orofacial cancer were implanted, followed by a dental prosthesis. The three
      phases of the protocol were a preoperative clinical and radiological analysis, a
      surgical phase under general anaesthesia and a postoperative clinical and
      radiological follow-up. RESULTS: Fifteen patients were treated for an oral cavity
      tumor, ten for a pharyngeal lesion, six for a laryngeal tumor and two for a
      maxillary cancer. The average dose of radiotherapy was 60.5 Gy. Sixty-eight
      implants were positioned, 91.9% in the anterior mandible. The delay between
      radiotherapy and implantation was 54 months. The delay between implantation and
      loading was seven months. The average follow-up was 31.9 months. No peri
      implantitis was observed. DISCUSSION: Implantation in irradiated bone is possible
      if a strict protocol is used; a good rate of success and improved quality of life
      will favour development of this technique. Criteria for dental implant placement
      include local and general conditions, the psychological situation and technical
      possibilities. Sufficient delay after radiotherapy is necessary to verify healing
      and the good prognosis of the cancer. The vascular supply can be preserved by
      implantation under general anesthesia. All patients were satisfied with the
      functional and esthetic results.

PMID- 16804480
TI  - [Flap techniques in secondary alveoloplasty: a comparison between two types of
      flap].
AB  - INTRODUCTION: The aim of this study was to compare two surgical soft tissue
      coverage techniques of secondary alveolar grafts in cleft lip and palate
      patients: the gingival mucoperiostal slidind flap and the mucosal rotation flap.
      MATERIAL AND METHOD: Fifty-two secondary alveolar bone grafts were
      retrospectively included in the study. Four clinical parameters were evaluated:
      post-operative dehiscence, oro-nasal fistula relapse, canine eruption through the
      graft and postoperative secondary periodontal procedures. RESULTS: Gingival
      mucoperiostal flaps had less postoperative dehiscence, more fistula relapse and
      needed less secondary periodontal procedures. DISCUSSION: Based on this study and
      on literature data, gingival mucoperiostal flap provides better quality of soft
      tissue coverage. Flap design doesn't influence canine eruption. Bone graft
      complications are increased with poor oral hygiene, if canine eruption occurred
      before surgery and in older patients.

PMID- 16804481
TI  - [Tuberculosis of the parotid gland].
AB  - INTRODUCTION: The aim of this study is to emphasize the difficulties of
      diagnosing parotid gland tuberculosis because of its non specific symptoms and to
      incite the physician to seek it more frequently. MATERIAL AND METHOD: Six cases
      of parotid gland tuberculosis were diagnosed within a 4-year period and included
      in a retrospective study. RESULTS: There were two men and four women, mean age 45
      years. Four patients underwent superficial parotidectomy with frozen section
      analysis which enabled us to rectify the diagnosis. Medical treatment was based
      on a 6-month course of bactericidal chemotherapy. Outcome was favorable in all
      the cases with nine months average follow. DISCUSSION: Symptoms of parotid gland
      are misleading, pathologic findings are of increasing importance for diagnosis,
      which with the new serology techniques may improve further.

PMID- 16804482
TI  - [Mechanisms by which acute orofacial pain becomes chronic].
AB  - Pain is a complex, multidimensional experience encompassing sensory
      discriminative, cognitive, emotional and motivational dimensions. These
      dimensions in the orofacial region have particular expression since the face and
      mouth have special biological, emotional and psychological meaning to each
      individual. Orofacial pain is frequent. Epidemiological studies reveal a high
      prevalence of severe pain in syndromes such as temporomandibular disorders (TMD),
      burning mouth syndrome and toothaches, as well as an important role of
      psychosocial influences, contributing to the persistence of these syndromes. Many
      of the difficulties experienced by clinicians with the diagnosis and management
      of acute and chronic orofacial pain stem from a lack of recognition and
      understanding of these complex conditions, the various intricate bio-psycho
      social interactions and the neurobiology behind the chronicisation of acute pain.
      This text strives to review the important advances and insights into the
      peripheral processes by which noxious stimuli activates or modulates nociceptive
      afferent input into the brainstem, the neural pathways in the brainstem and
      higher levels of the trigeminal (V) somatosensory system and the mechanisms
      involved in the plasticity of nociceptive transmission. We shall link this
      knowledge to clinical correlates and suggest a therapeutic approach in acute
      orofacial pain, in the attempt to avoid the development of chronic pain.

PMID- 16804483
TI  - [Selective lymph node dissection].

PMID- 16804484
TI  - [Temporomandibular osteomyelitis secondary to progressive necrotizing otitis
      externa].
AB  - INTRODUCTION: Osteomyelitis of the temporomandibular joint is a rare complication
      of invasive external otitis, often occurring after inappropriate initial
      treatment of the causal affection. OBSERVATION: A 65-year-old diabetic man was
      treated for invasive otitis externa complicated by destructive osteomyelitis of
      the ipsilateral temporomandibular joint. The diagnosis was suspected clinically
      and confirmed by imaging. The course was favorable with medical treatment.
      DISCUSSION: Osteomyelitis is an extremely unusual complication of invasive otitis
      externa. Diffusion of the infection toward the temporomandibular joint can be
      secondary to an osteitis of the bony canal or spread via congenital dehiscences
      of the external auditory canal. Pain, limitation of mouth opening and auricular
      swelling are the main clinical signs. Treatment is essentially medical, based on
      adapted antibiotic therapy.

PMID- 16804485
TI  - [Giant ameloblastoma of the mandible].

PMID- 16804486
TI  - [Patient follow-up after orthognathic surgery. Interview by Michel Richter].

PMID- 16804487
TI  - [Palatine ulcer].

PMID- 16804488
TI  - [Halitosis and polyphenols].

PMID- 16804493
TI  - Editorial: GOOD NEWS OR BAD? The processes of revision of the classifications of
      mental disorders have started.

PMID- 16804494
TI  - Cognitive deficit in schizophrenia: comparative analysis of positive and negative
      subtype and predictors of positive subtype.
AB  - OBJECTIVE: The objective of the study was to investigate the global cognitive
      deficit in schizophrenia and to compare cognitive dysfunction in the positive and
      negative subtypes of schizophrenia, and furthermore to examine the existence of
      predictors of the positive and negative subtypes of schizophrenia. METHOD: 56
      patients with schizophrenia were evaluated with the Positive and Negative
      Syndrome Scale to classify them into the subtypes of schizophrenia, that is
      positive subtype (31 patients) and negative subtype (25 patients). All the
      patients were entering into remission. To examine the cognitive deficits in
      schizophrenia (global and selective) we compared scores on the Wechsler
      Individual Intelligence Test (VITI) for the positive and negative subtypes.
      RESULTS: The negative subtype of schizophrenia showed significantly higher
      cognitive dysfunction in comparison to the positive subtype, with reduced
      functioning in evolutionary higher cognitive functions like the selection of
      information, processing, planning, comprehension, realization (executive
      functions) as well as visual motor abilities. Verbal IQ predicts the positive
      subtype of schizophrenia.

PMID- 16804495
TI  - Individuals with diabetes mellitus with and without depressive symptoms: could
      social network explain the comorbidity?
AB  - OBJECTIVES: The main objective of the present study was to obtain an approximate
      prevalence of depressive symptoms in a community sample of persons with diabetes
      mellitus and to discover whether social networks could explain comorbidity of
      diabetes mellitus and depressive symptoms. METHOD: Subjects were persons with
      diabetes mellitus, members of the Diabetes Association of Ljubljana (N = 396,
      average age: 62.9 +/- 13.4, average duration of diabetes: 17.2 +/- 10.6).
      Firstly, subjects were screened with CESD (Centre for Epidemiological Studies
      Depression Scale) and demographic data were also gathered. Secondly, two samples
      (individuals with and without depressive symptoms) were compared on the basis of
      social network analysis. RESULTS: The prevalence of depressive symptoms was
      higher among persons with diabetes in comparison with general population.
      Individuals with depressive symptoms compared with individuals without depressive
      symptoms were less dissatisfied with diabetes (p = 0.011), and had better
      informational (p = 0.039) and instrumental support (p = 0.046), relations between
      them and support givers were closer (p = 0.050), more important and less
      conflicting (p = 0.042). Compared groups did not differ in quantitative
      characteristics of social networks (eg. size of the network or the network gender
      structure). CONCLUSIONS: The community sample results in Slovenia support the
      already reported association between diabetes mellitus and depression.
      Furthermore, social network analysis offered some potentially relevant
      explanation for comorbidity of diabetes mellitus and depressive symptoms.

PMID- 16804497
TI  - Psychosocial aspects of acquired hearing impairment in the patients with
      otosclerosis.
AB  - Currently available evidence reveals comparatively few studies of the
      psychological and social effects of acquired hearing impairment, in spite of the
      fact that clinicians have for a long time been aware of a connection between
      acquired hearing impairment and mental disorders. The existing data indicate that
      psychological disorders are significantly more frequent in a population with
      hearing impairment than in the average population and are accompanied by
      disharmony in interpersonal and social relations. AIM: Establishing the presence
      and the type of mental disorders in patients with hearing impairment due to
      otosclerosis, before and 6 months after corrective surgery, as well as finding
      the role of adaptation style (personal adjustment) and facing strategy
      (communication strategies) as mediating variables between the acquired hearing
      impairment and observed psychical changes. METHODOLOGY: in 60 subjects, potential
      candidates for stapedectomy, MMPI-201 has been applied before and after surgery,
      in order to evaluate the mental state. For assessments of personal adjustment to
      the impairment and communication strategies, a communication personal profile has
      been applied preoperatively. RESULTS: more psychiatric disorders are present in
      the preoperative group compared to the general population and the postoperative
      group. These disorders are of exclusively a neurotic nature; the most frequent
      are depressive, anxious depressive and anxious reactions. A connection was found
      between adaptation style and facing strategies whether in the presence or absence
      of psychological disorders. CONCLUSION: the findings indicate a need for
      professional psychiatric-psychological support as a part of a rehabilitation
      program designed to reduce psychological difficulties, i.e. to help individuals
      to become adapted to the acoustic environment and to prevent or at least minimize
      the negative consequences of hearing impairment by efficient communication
      strategies.

PMID- 16804496
TI  - Family physicians' views on disclosure of a diagnosis of cancer and care of
      terminally ill patients in Croatia.
AB  - INTRODUCTION: Family physicians have a crucial role in communication and
      palliative care for terminally ill patients. AIMS: To examine family physicians'
      views about the disclosure of the diagnosis and information about cancer to their
      patients and to their families; to establish the most appropriate person to
      deliver the diagnosis of cancer to the patient; to examine whether family
      physicians cooperate with palliative care associations, and to assess their
      opinions about euthanasia and emotional support to dying patients. SUBJECTS AND
      METHODS: One hundred and thirty four family physicians participated in the study.
      The data was collected by questionnaire designed for this survey about cancer
      care. RESULTS: The majority of respondents 96 (71.64%) delivered the cancer
      diagnosis to their patients sometimes, and 69 (51.5%) told the truth about the
      cancer diagnosis to the family without the patient's permission. The respondents
      90 (70.3%) considered that the family physician was the most appropriate person
      to disclose the cancer diagnosis and 107 (80.5%) considered that the patients'
      home was the most appropriate place for terminal care. The majority of physicians
      61 (45.5%) thought that they did not cooperate enough with palliative care
      associations. In working with terminal patients, 42 (32.1%) respondents
      considered communication with the patients to be particularly difficult and 122
      (93.8%) thought that emotional support of family and friends was most important.
      CONCLUSION: The majority of physicians deliver a diagnosis of cancer to their
      patients occasionally, and they also tell it to the patient's family. They
      considered family physician to be the most appropriate person to disclose a
      diagnosis of cancer and the patient's home was considered the most appropriate
      place for terminal care. In caring for terminally ill patients communication is
      considered particularly difficult, and the emotional support of family and
      friends is considered most important.

PMID- 16804499
TI  - Suicide in the capital of Serbia and Montenegro in the period 1997-2004 - sex
      differences.
AB  - There are very few investigations about sex differences in suicide which include
      some other variables (e.g. age, profession etc). Data which concern suicide sex
      differences are obscure and usually are given in statistical accounts of causes
      of death. The aim of our study was to investigate sex differences in realized
      suicides within the city of Belgrade during the last eight year period. Data was
      taken from the index records of suicide in the city of Belgrade held at the
      Institute for Informatics and Statistics. We took sex as the main observed
      variable, and analyzed nine other variables as related to sex. Statistical
      analysis was done by using the crude specific rate. The variability of the rate
      was estimated by computing a confidence interval. The results of our study gave
      the profile of males and females who committed suicide in Belgrade in the period
      of the last eight years. Although there were significant quantitative
      differences, the female/male profile of completed suicides is similar, and
      differs only in the method of suicide: both males and females choose hanging,
      drowning and suffocation as the most common method of suicide, while poisoning is
      on the second most common method chosen by females and firearms the second most
      common method for males. The frequency of suicide, in both sexes, showed a
      tendency to decrease over the observed period (the highest suicide rate was in
      2000- females 9.7, males 19.7, and the lowest in 2004- females 4.5 males 9.1).
      Male to female suicide rate ratio was 2 to 1. Sex differences were registered in
      all of the observed nine variables.

PMID- 16804498
TI  - Forms of parasuicide in young people in Bosnia.
AB  - OBJECTIVE: This study is an investigation of parasuicidal presentations in young
      people in Bosnia during the period from 1992 to 2004. The other aims were: an
      analysis of the stress as well as the personal and emotional traits of suicidal
      subjects. METHODS: Two groups of young people were investigated: 90 with
      parasuicidal caracteristics and 90 controls who had experienced emotional and
      behavioral crises during adolescence. The study is longitudinal and stratified
      according to the qualities of the parasuicidal behaviour. The tests used in this
      study (LOP, Ci, CMI, EPQ-98 and P.I.E.) are statistically elaborated by standard
      descriptive and analytical methods. RESULTS: The results show the following
      factors to be highly significant: destruction and violence inside the families (p
      < 0.001) as well as migration and heredity (p < 0.05). Discriminative analysis
      (rc) confirmed group difference in neuroticism = 0.95541, F=38.321 with
      significance factor of p < 0.001. EPQ test in parasuicidal subjects shows high
      level of neuroticism and psychoticism while controls show extroversion and
      conformism. Canonical Fcn = 0.6634, rc = 0.771, df = 4 chi(2) = 85.73, p < 0.001.
      P.I.E. clearly differentiated parasuicidal group from adolescent, control group:
      Hi quadrant test chi(2) = 101.361 and statistical significance p < 0.001. Results
      show: 1. suicide: n = 7 (7.7%), parasuicide: n = 84 (43.6%) and maturation: n =
      89 (48.9%). CONCLUSION: Representation of parasuicidal behaviour was found in
      both groups of examinees, but the forms are more represented in parasuicide.
      Sociodemographic difference between the examined groups was proved, and stress,
      personal and emotional structures of parasuicide were confirmed by discrimination
      analysis. Auto-destructivity shows even quicker forms of destruction and longer
      forms of self-destruction.

PMID- 16804501
TI  - The use of card sort exercises in the prevention of relapse in serious mental
      illness.
AB  - The identification of early warning signs and the development of a relapse
      prevention plan is an important part of the treatment of serious mental illness,
      be it Schizophrenia or bipolar affective disorder. The use of a card sort
      exercise is an effective way of developing an accurate description of the early
      warning signs. This paper reviews the literature on the subject, and describes
      our method of applying this technique to our patients. It also describes a pilot
      study in which we found that the use of early warning signs in an early
      intervention service does enable some relapses to be treated at home before they
      become so serious as to lead to hospital admission. We look forward to further
      studies on large groups of patients.

PMID- 16804500
TI  - Comorbidity of schizophrenia and cancer: clinical recommendations for treatment.
AB  - The paper analyzes some issues on the comorbidity between schizophrenia and
      cancer. Epidemiological studies have reported contradictory results, but it is
      certain that patients with schizophrenia are more likely to suffer from risk
      factors for cancer development, such as increased alcohol abuse, obesity,
      nicotine dependence and decreased physical activity. The paper gives guidelines
      for the treatment of cancer in patients with schizophrenia, and discusses
      possible interactions between chemotherapy and psychotropic drugs. Particular
      attention is paid to the use of antipsychotics which increase the level of
      prolactin, in view of the possible risk of breast and endometrial cancer in
      patients with schizophrenia.

PMID- 16804502
TI  - Post-war mental health promotion in Bosnia-Herzegovina.
AB  - After the war in Bosnia-Herzegovina, mental illness is very prevalent. With
      little knowledge about mental health, the stigma of mental illness is still
      pervasive in many communities. To combat this prejudice, we describe mental
      health promotion strategies which can empower individuals and educate the
      communities in which they live.

PMID- 16804503
TI  - [The importance of family coherence for mentally handicapped children].
AB  - A lack of perseverance, attention and poor modulated behaviour are important
      criterions of handicapped children (Dilling et al. 1993). Therefore, instructions
      have to be repeated quite often, sometimes even by different family members. For
      this reason, good family coherence might reduce symptoms significantly (Dopfner
      and Lehmkuhl 1995). The handicapped child might cause less disagreement in
      families with good coherence, which improves family;s features (Saile et al.
      1995). Families of 15 handicapped children were included for evaluation and
      compared with a matched, healthy control group. Parents were asked to complete a
      form assessing the family;s features ("Familienklima-Testsystem", Schneewind et
      al. 1985), "Erziehungspraktiken", (Schneewind et al. 1985). Group comparison was
      made by the Mann-Whitney-U-Test. Our results strongly suggest, that good
      coherence seems to have positive effects on family;s features, especially by
      handicapped children. So we think, that on the one hand good coherence might
      reduce symptomatology and that on the other hand family's features have
      protective effects on handicapped children.

PMID- 16804504
TI  - Serotonin transporter polymorphism in Croatian patients with major depressive
      disorder.
AB  - OBJECTIVES: Differences in serotonin transporter (SERT) expression and function
      produced by gene polymorphisms are associated with several behavioral and
      psychiatric traits. Two polymorphic regions of SERT gene: a 44-base-pair (bp)
      insertion / deletion polymorphism in the promoter region (SERTPR), and variable
      number of tandem repeats (VNTR) in second intron (SERT-in2) have been
      characterized. In this study we investigated the frequency distribution of
      polymorphic variants of short (S, s) and long (L, l) alleles, genotypes and
      haplotypes of SERTPR, and SERTin2, in patients with major depressive disorder
      (MDD) and compared it with results obtained from the Croatian healthy population.
      SUBJECTS AND METHODS: one hundred and fourteen patients who fulfilled DSM-IV
      criteria for a diagnosis of MDD were included in the study. Comparisons were made
      with the results obtained for 120 healthy volunteers representing a mixed
      Croatian population. SERT genotyping was performed by the PCR (polymerase-chain
      reaction) method. RESULTS: The frequency distribution of L and S alleles and
      genotypes of SERTPR was not statistically different between MDD patients and
      control participants. The proportion of SERT-in2 short (s) alleles was
      significantly higher among MDD patients in comparison to healthy subjects (p =
      0.04). CONCLUSION: "s" allele variant in the intron 2 of SERT gene could be
      associated with susceptibility to MDD.

PMID- 16804505
TI  - Oxcarbazepine in a carbamazepine-intolerant patient with bipolar affective
      disorder: a case report.

PMID- 16804506
TI  - Chiari I malformation in adults: epileptiform events and schizophrenia-like
      psychosis.
AB  - We would like to report on a very interesting clinical case of recurrent
      psychotic events caused with Chiari I malformation in adults. The mediosagital
      reconstruction of MR image of the brain and cranio-cervical region is the most
      important diagnostic approach in finding the cause of epileptiform events,
      neurological signs and psychotic illness caused by Chiari malformation.

PMID- 16804507
TI  - Series of seizures as a sign of development of recurrent malignant neuroleptic
      syndrome - a case report.
AB  - Neuroleptic malignant syndrome (NMS) is an uncommon but sometimes fatal
      complication of neuroleptics and other medications that involve the central
      dopaminergic system. Many diagnostic criteria have been proposed for NMS but
      because of its variable presentation, universal criteria have not been
      established yet. Hyperthermia, disturbances of consciousness, extrapyramidal and
      autonomic symptoms are common features of NMS. We report the case of a 36 years
      old woman suffering from chronic schizophrenia and treated with flufenazine and
      olanzapine, who presented with series of generalised tonic-clonic seizures as the
      acute onset of recurrent malignant neuroleptic syndrome. Although atypical
      neuroleptics were previously thought to have less risk for MNS, combination of
      conventional and atypical neuroleptics in therapy increases the risk of NMS
      development and olanzapine might be responsible for the epileptic manifestations
      at the onset of fulminant NMS.

PMID- 16804508
TI  - Disturbed family relations as a source of uncontrolled aggressiveness in early
      adolescence.
AB  - This paper is a casuistic presentation of a clinical case of an adolescent with
      behavioural disorder. Unelaborated aggressiveness dominates the clinical picture.
      The case history, the plan and the course of the therapy are included. The paper
      concludes with the elaboration of psychodynamics attitude, which has close ties
      with the overall family dynamics.

PMID- 16804509
TI  - Psychosis and Wilson's disease: a case report.
AB  - In this article we present a case of a 26-year-old woman with clinical picture of
      acute psychosis, as the first and main manifestation of Wilson's disease, who
      developed abnormal involuntary choreoathetoid limb movements, few days after
      initiation of neuroleptic therapy. At the first movement neurological symptoms
      were misinterpreted as side effect of haloperidol, but consulted neurologist
      suggested additional diagnostic procedure which confirmed Wilson's disease.
      Psychiatric symptomatology and abnormal involuntary movements were the clinical
      manifestation of this disease, which improved with neuroleptic and chelating
      treatment. Interdisciplinary approach with good collaboration of psychiatrists
      and neurologists is crucial for Wilson's disease, because early diagnosis and
      treatment without delay is critical to the prognosis. This case serves as a
      reminder that involuntary movements can be side effect of antipsychotics but also
      the clinical manifestation of some illnesses, for example Wilson's, Huntington's
      and Fuhr's diseases.

PMID- 16804510
TI  - The relief of pain as a human right.

PMID- 16804511
TI  - The influence of metals on the expression of surface antigens on human
      lymphocytes in vitro.
AB  - OBJECTIVES: Metals have different effects on the immune functions. Through the
      experimental in vitro model, we studied the changes in the activation and co
      stimulatory surface markers in human lymphocytes cultivated with selected metal
      salts. METHODS: Whole human blood was cultivated with cadmium (Cd) or zinc (Zn)
      sulfate for 18 hours. The number of lymphocytes positive for activation and co
      stimulatory markers was evaluated by flow cytometry. RESULTS: Elevation of the
      CD69 and CD23 markers as well as higher expression of CD28 was found in cultures
      of lymphocytes incubated with Cd. In cultures incubated with Zn, minor elevation
      of the HLA-DR antigen expression was observed in comparison to Cd-treated cell
      cultures. Decrease of CD3 expression was observed after cultivation with both Cd
      and Zn salts. CONCLUSION: Cd and Zn exhibit different effects on the expression
      of human surface activation antigens and co-stimulatory molecules. Cd in non
      toxic concentrations stimulated expression of early activation molecules and
      therefore could change the early phase of immune response. This was not the case
      for Zn, where the results were similar to untreated cell cultures.

PMID- 16804512
TI  - Removal of dental amalgam decreases anti-TPO and anti-Tg autoantibodies in
      patients with autoimmune thyroiditis.
AB  - OBJECTIVES: The impact of dental amalgam removal on the levels of anti-thyroid
      peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies was studied in
      patients with autoimmune thyroiditis (AT) with and without mercury allergy.
      METHODS: Thirty-nine patients with AT were tested by an optimized lymphocyte
      proliferation test MELISA for allergy (hypersensitivity) to inorganic mercury.
      Patients were divided into two groups: Group I (n = 12) with no hypersensitivity
      to mercury and Group II (n = 27) with hypersensitivity to mercury. Amalgam
      fillings were removed from the oral cavities of 15 patients with hypersensitivity
      to mercury (Group IIA) and left in place in the remaining 12 patients (Group
      IIB). The laboratory markers of AT, anti-TPO and anti-Tg autoantibodies, were
      determined in all groups at the beginning of the study and six months later.
      RESULTS: Compared to levels at the beginning of the study, only patients with
      mercury hypersensitivity who underwent amalgam replacement (Group IIA) showed a
      significant decrease in the levels of both anti-Tg (p=0.001) and anti-TPO
      (p=0.0007) autoantibodies. The levels of autoantibodies in patients with or
      without mercury hypersensitivity (Group I and Group IIB) who did not replace
      amalgam did not change. CONCLUSION: Removal of mercury-containing dental amalgam
      in patients with mercury hypersensitivity may contribute to successful treatment
      of autoimmune thyroiditis.

PMID- 16804513
TI  - Micro analysis of metals in dental restorations as part of a diagnostic approach
      in metal allergies.
AB  - In dentistry, a variety of potentially allergenic metals are used, such as
      mercury, palladium, nickel, gold, chromium, cobalt and other metals. This paper
      describes a diagnostic approach from a dentist's point of view, which enables
      analysis of metals in a patient's oral cavity. If metal allergy is suspected, a
      micro analysis can be used to determine which metals are present in the
      restorations. When the exact composition of the dental materials is known, the
      patient can be tested in vivo (patch test) and/or in vitro (lymphocyte
      proliferation test) to reveal sensitization. Two patients with nickel allergy are
      described where removal of nickel-containing materials (bridge and orthodontic
      wire) resulted in the marked alleviation of symptoms and improvement of health.
      Finally, if allergy to specific metals has been established, the restorations
      containing the implicated metals should be removed to discontinue the exposure
      and thus facilitate the patient's health.

PMID- 16804514
TI  - Metal alloys in the oral cavity as a cause of oral discomfort in sensitive
      patients.
AB  - OBJECTIVE OF THE STUDY: The occurrence of galvanism with its heterogeneous
      symptomatology is often the source of considerable problems. Abrasion and
      corrosion not only damage dental alloys but also burden the organism by release
      of metallic particles. The objective of this study is to evaluate the hypothesis
      that measurement of galvanic currents could be a useful diagnostic method.
      PATIENT GROUPS AND METHODOLOGY: Three hundred fifty-seven persons with dental
      metal restorations were divided into groups according to abnormal values of
      galvanic currents and by oral discomfort. In all persons a detailed examination
      of the oral cavity was performed, and galvanic currents were measured. In one
      hundred fifty-nine patients abnormal galvanic currents were found. Measurement of
      metallic elements in saliva was performed in these patients and in a group of 21
      healthy volunteers without any metals in the oral cavity. Thirty-three patients
      agreed to treatment which involved removal of the causative alloys and their
      replacement by non-metallic restorations. RESULTS: No correlation was found
      between the values of measured currents and the number of teeth treated by metal
      restorations. However, patients with metal restorations had significantly higher
      contents not only of mercury, but also of tin, silver, copper, and gold in the
      saliva than patients without metallic restorations. After removal of the electro
      active restorations, both the contents of metals in saliva and galvanic currents
      decreased in comparison with the levels before the treatment. CONCLUSIONS:
      Galvanic effects as well as metal particles may induce a series of local or
      systemic pathological phenomena in sensitive individuals. The occurrence of
      pathologically acting galvanic effects is influenced not only by the composition
      and combination of different dental alloys, but to a significant degree also by
      the quality of used materials and processing.

PMID- 16804515
TI  - Increased levels of transition metals in breast cancer tissue.
AB  - OBJECTIVES: High levels of transition metals such as iron, nickel, chromium,
      copper, and lead are closely related to free radical generation, lipid
      peroxidation, formation of DNA strand breaks, and tumor growth in cellular
      systems. In order to determine the correlation to malignant growth in humans, we
      investigated the accumulation of heavy metals in 20 breast cancer biopsies and
      compared the findings to the levels found in 8 healthy biopsies. METHODS: The
      concentration of transition metals in breast cancer and control biopsies was
      assessed by a standardized Atomic Absorption Spectrofotometry technique with
      acidic hydrolysis for sample preparation. Additionally, heavy metal analysis in
      control biopsies was also performed with an Inductive Coupled Plasma--Mass
      Spectroscopy technique. For statistical analysis of the results, the Mann-Whitney
      U Test was applied. RESULTS: A highly significant accumulation of iron
      (p<0.0001), nickel (p<0.00005), chromium (p<0.00005), zinc (p<0.00001), cadmium
      (p<0.005), mercury (p<0.005), and lead (p< 0.05) was found in the cancer samples
      when compared to the control group. Copper and silver showed no significant
      differences to the control group, whereas tin, gold, and palladium were not
      detectable in any biopsies. CONCLUSIONS: The data suggest that pathological
      accumulation of transition metals in breast tissue may be closely related to the
      malignant growth process.

PMID- 16804516
TI  - Autoimmune thyroiditis and Helicobacter pylori--is there a connection?
AB  - OBJECTIVES: In this study we examined the anti-Helicobacter pylori (anti-H.
      pylori) antibodies in patients with autoimmune thyroiditis, with and without
      different polyglandular involvement, and in healthy controls. MATERIAL & METHODS:
      Patients with autoimmune thyroiditis (AT) were divided into three groups: Group
      A: 23 patients with isolated AT, Group B: 30 patients with AT as a part of
      polyglandular activation of autoimmunity, and Group C: 7 patients with AT as a
      part of autoimmune polyglandular syndrome type II. Thirty healthy individuals
      served as controls (Group D). Anti-H. pylori antibodies were determined first by
      ELISA for classes IgG, IgA, and IgM, and subsequently by immunoblot for classes
      IgG and IgA. RESULTS: ELISA: The number of patients with IgA antibodies in Group
      A (39%) and Group B (30%) differed significantly from controls (7%, p<0.05).
      Immunoblot: Anti-CagA antibodies were found in 13% of patients in Group A, 7% of
      Group B, 0% of Group C, and 20% of Group D. A higher seroprevalence, as compared
      to controls, was found for IgG to the VacA (p=0.01), 30 kDa (p=0.001), and 17 kDa
      (p=0.008) antigens in Group A and for IgG to the 30 kDa antigen in Group C
      (p=0.037). A significantly higher seroprevalence, as compared to controls, was
      likewise found for IgA to the 17 kDa antigen in Group A (p=0.015). CONCLUSIONS: A
      different distribution of antibodies to H. pylori antigens was found in patients
      with isolated AT compared to patients with AT coupled with a polyglandular
      syndrome.

PMID- 16804517
TI  - Association of MUTYH and colorectal cancer.
AB  - Mutations in the MUTYH gene have been reported to be associated with increased
      risk of developing colorectal cancer. In this study, we confirmed this
      association using original data on 928 colorectal cancer cases and 845 healthy
      controls from Scotland. We then conducted a meta-analysis from published data on
      the association between mutations at MUTYH and colorectal cancer risk. We show
      for the first time a small but significant mono-allelic effect with a genotype
      relative risk (GRR) of 1.27 (95% confidence interval (CI): 1.01-1.61), and
      confirm and give a more precise estimate of the strong bi-allelic effect with an
      estimated GRR of 117 (95% CI: 74-184). This study underscores the need for large
      sample sizes in order to identify small gene effects when the disease allele
      frequency is low.

PMID- 16804518
TI  - A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent
      glioblastoma multiforme.
AB  - Delta(9)-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth
      and angiogenesis in animal models, so their potential application as antitumoral
      drugs has been suggested. However, the antitumoral effect of cannabinoids has
      never been tested in humans. Here we report the first clinical study aimed at
      assessing cannabinoid antitumoral action, specifically a pilot phase I trial in
      which nine patients with recurrent glioblastoma multiforme were administered THC
      intratumoraly. The patients had previously failed standard therapy (surgery and
      radiotherapy) and had clear evidence of tumour progression. The primary end point
      of the study was to determine the safety of intracranial THC administration. We
      also evaluated THC action on the length of survival and various tumour-cell
      parameters. A dose escalation regimen for THC administration was assessed.
      Cannabinoid delivery was safe and could be achieved without overt psychoactive
      effects. Median survival of the cohort from the beginning of cannabinoid
      administration was 24 weeks (95% confidence interval: 15-33). Delta(9)
      Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased
      tumour-cell Ki67 immunostaining when administered to two patients. The fair
      safety profile of THC, together with its possible antiproliferative action on
      tumour cells reported here and in other studies, may set the basis for future
      trials aimed at evaluating the potential antitumoral activity of cannabinoids.

PMID- 16804519
TI  - Cancer risk after radiotherapy for breast cancer.
AB  - Among women with breast cancer, we compared the relative and absolute rates of
      subsequent cancers in 1541 women treated with radiotherapy (RT) to 4570 women not
      so treated (NRT), using all registered in the Swiss Vaud Cancer Registry in the
      period between 1978 and 1998, and followed up to December 2002. Standardised
      incidence ratios (SIRs) and the corresponding 95% confidence intervals (CIs) were
      based on age- and calendar year-specific incidence rates in the Vaud general
      population. There were 11 lung cancers in RT (SIR = 1.40; 95% CI: 0.70-2.51) and
      17 in NRT women (SIR = 0.76; 95% CI: 0.44-1.22), 72 contralateral breast cancers
      in RT (SIR = 1.85; 95% CI: 1.45-2.33) and 150 in NRT women (SIR = 1.38; 95% CI:
      1.16-1.61), and 90 other neoplasms in RT (SIR = 1.37; 95% CI: 1.10-1.68) and 224
      in NRT women (SIR = 1.05; 95% CI: 0.91-1.19). Overall, there were 173 second
      neoplasms in RT women (SIR = 1.54, 95% CI: 1.32-1.78) and 391 among NRT women
      (SIR = 1.13, 95% CI: 1.02-1.25). The estimates were significantly heterogeneous.
      After 15 years, 20% of RT cases vs 16% of NRT cases had developed a second
      neoplasm. The appreciable excess risk of subsequent neoplasms after RT for breast
      cancer must be weighed against the approximately 5% reduction of breast cancer
      mortality at 15 years after RT.

PMID- 16804520
TI  - STAT3 is required but not sufficient for EGF receptor-mediated migration and
      invasion of human prostate carcinoma cell lines.
AB  - Growth factor-induced migration is a rate-limiting step in tumour invasiveness.
      The molecules that regulate this cellular behaviour would represent novel targets
      for limiting tumour cell progression. Epidermal growth factor (EGF) receptor
      (EGFR)-mediated motility, present in both autocrine and paracrine modes in
      prostate carcinomas, requires de novo transcription to persist over times greater
      than a few hours. Therefore, we sought to define specific signalling pathways
      that directly alter cellular transcription. Signal transducer and activator of
      transcription 3 (STAT3) is activated, as determined by electrophoretic motility
      shift assays, by EGFR in DU145 and PC3 human prostate carcinoma cells in addition
      to the motility model NR6 fibroblast cell line. Inhibition of STAT3 activity by
      antisense or siRNA downregulation or expression of a dominant-negative construct
      limited cell motility as determined by an in vitro wound healing assay and
      invasiveness through a extracellular matrix barrier. The expression of
      constitutively activated STAT3 did not increase the migration, which indicates
      that STAT3 is necessary but not sufficient for EGFR-mediated migration. These
      findings suggest that STAT3 signalling may be a new target for limiting prostate
      tumour cell invasion. In a microarray gene analysis of what transcription units
      are altered by EGF in a STAT3-dependent manner we found that the expression of
      motility-limiting VASP protein and the apoptosis nexus caspase 3 were both
      downregulated upon EGF exposure. These findings suggest a molecular basis for the
      STAT3 dependence of EGFR-mediated prostate tumour progression.

PMID- 16804522
TI  - Increased risk of second malignancies after in situ breast carcinoma in a
      population-based registry.
AB  - Among 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972
      2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma
      in situ patients exhibited a two-fold increased risk of second cancer
      (standardised incidence ratios (SIR): 2.1, 95% confidence interval (CI): 1.7
      2.5). The risk was highest for a second breast cancer (SIR: 3.4, 95% CI: 2.6-4.3;
      AER: 66 patients per 10,000 per year) followed by skin cancer (SIR: 1.7, 95% CI:
      1.1-2.6; AER: 17 patients per 10,000 per year). The increased risk of second
      breast cancer was similar for the ipsilateral (SIR: 1.9, 95% CI: 1.3-2.7) and
      contralateral (SIR: 2.0, 95% CI: 1.4-2.8) breast. Risk of second cancer was
      independent of age at diagnosis, type of initial therapy, histologic type of BCIS
      and period of diagnosis. Standardised incidence ratios of second cancer after
      BCIS (SIR: 2.3, 95% CI: 1.8-2.8) resembled that after invasive breast cancer
      (SIR: 2.2, 95% CI: 2.1-2.4). Surveillance should be directed towards second (ipsi
      and contra-lateral) breast cancer.

PMID- 16804521
TI  - Large needle aspiration biopsy and galectin-3 determination in selected thyroid
      nodules with indeterminate FNA-cytology.
AB  - Thyroid fine-needle aspiration biopsy (FNA)-cytology is widely used for the
      preoperative characterisation of thyroid nodules but this task is difficult for
      follicular lesions, which often remain undefined. We propose a strategy for
      improving the preoperative characterisation of selected follicular thyroid
      proliferations, which is based on large needle aspiration biopsy (LNAB) and
      galectin-3 expression analysis. Eighty-five thyroid specimens were obtained by
      LNAB (20-gauge needles) from thyroid nodules with indeterminate follicular FNA
      cytology. Aspirated material was processed as a tissue microbiopsy to obtain cell
      blocks for both cyto/histo-morphological evaluation and galectin-3 expression
      analysis, by using a purified monoclonal antibody to galectin-3 and a biotin-free
      immunoperoxidase staining method. Preoperative diagnosis was compared to the
      final histology. LNAB and cell-block technique allow a preliminary distinction
      between nodules with a homogeneous microfollicular/trabecular structure, as
      frequently observed in tumours, and lesions with mixed normo-micro
      macrofollicular architecture, as observed in goitre. Furthermore, LNAB provides
      optimal substrates for galectin-3 expression analysis. Among 85 cases tested, 14
      galectin-3-positive cases were discovered preoperatively (11 thyroid cancers and
      three adenomas confirmed at the final histology), whereas galectin-3-negative
      cases were 71 (one carcinoma and 70 benign proliferations at the final
      histology). Sensitivity, specificity and diagnostic accuracy of this integrated
      morphologic and phenotypic diagnostic approach were 91.6, 97.2 and 95.3%,
      respectively. In conclusion, LNAB plus galectin-3 expression analysis when
      applied preoperatively to selected thyroid nodules candidate to surgery can
      potentially reduce unnecessary thyroid resections.

PMID- 16804523
TI  - No association between green tea and prostate cancer risk in Japanese men: the
      Ohsaki Cohort Study.
AB  - In a prospective study of 19,561 Japanese men, green-tea intake was not
      associated with a lower risk of prostate cancer (110 cases), the multivariate
      hazard ratio for men drinking > or =5 cups compared with <1 cup per day being
      0.85 (95% confidence interval 0.50-1.43, trend P = 0.81).

PMID- 16804524
TI  - An open, multi-centre, phase II clinical trial to evaluate the efficacy and
      safety of paclitaxel, UFT, and leucovorin in patients with advanced gastric
      cancer.
AB  - The aim of the study was to evaluate the response rate and safety of weekly
      paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5
      fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in
      patients with advanced gastric cancer. Patients with histologically confirmed,
      locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel
      1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2)
      day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days,
      followed by a 7-day period without treatment. Treatment was repeated every 21
      days. From February 2003 to October 2004, 55 patients were enrolled. The median
      age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour
      response, two achieved a complete response and 22 a partial response, with an
      overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients
      were evaluated for survival and toxicities. Median time to progression and
      overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4
      toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients
      (15%). Although treatment was discontinued owing to treatment-related toxicities
      in nine patients (16%), there was no treatment-related mortality. Weekly
      paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in
      treating patients with advanced gastric cancer.

PMID- 16804525
TI  - Intensive follow-up after liver resection for colorectal liver metastases:
      results of combined serial tumour marker estimations and computed tomography of
      the chest and abdomen - a prospective study.
AB  - The aim of the study was to prospectively evaluate an intensive follow-up
      programme using serial tumour marker estimations and contrast-enhanced computed
      tomography (CT) of the chest and abdomen in patients undergoing potentially
      curative resection of colorectal liver metastases. Seventy-six consecutive
      patients having undergone potentially curative resections of colorectal liver
      metastases in a single unit were followed up with a protocol of 3 monthly
      carcinoembryonic antigen and carbohydrate antigen 19-9 estimations and contrast
      enhanced spiral CT of the chest, abdomen and pelvis for the first 2 years
      following surgery and 6 monthly thereafter. The median period of follow-up was 24
      months (range 18-60). Recurrent tumour was classed as early if within 6 months of
      liver resection. Thirty-seven of the 76 patients (49%) developed recurrence on
      follow-up. Nineteen recurrences were in the liver alone (51%), 16 liver and
      extrahepatic (43%) and two extrahepatic alone (6%). Of the 19 patients with
      isolated liver recurrence, eight developed within 6 months of liver resection
      none of which were resectable. Of the 11 recurrences after 6 months, five (45%)
      were resectable. Of the 37 recurrences, CT indicated recurrence despite normal
      tumour markers in 19 patients. Tumour markers suggested recurrence before imaging
      in 12 and concurrently with imaging in 6. In the 12 patients who presented with
      elevated tumour markers before imaging, there was a median lag period of 3 months
      (range 1-21) in recurrence being detected on further serial imaging. Seventeen
      patients who developed recurrence had normal tumour markers before initial
      resection of their liver metastases. Of these 17, 10 (58%) had an elevation of
      tumour markers associated with recurrence. Over a median follow-up of 2 years
      following liver resection, the use of CT or tumour markers alone would have
      failed to demonstrate early recurrence in 12 and 18 patients respectively. A
      combination of tumour markers and CT detected significantly more (P < 0.05)
      recurrence than either modality alone. Tumour markers and CT should be used in
      combination in the follow-up of patients with resected colorectal liver
      metatases, including patients whose markers are normal at the time of initial
      liver resection.

PMID- 16804526
TI  - The clinical and economic benefits of capecitabine and tegafur with uracil in
      metastatic colorectal cancer.
AB  - Two oral fluoropyrimidine therapies have been introduced for metastatic
      colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a
      combination of tegafur and uracil administered together with leucovorin. The
      purpose of this study was to compare the clinical effectiveness and cost
      effectiveness of these oral therapies against standard intravenous 5-fluorouracil
      regimens. A systematic literature review was conducted to assess the clinical
      effectiveness of the therapies and costs were calculated from the UK National
      Health Service perspective for drug acquisition, drug administration, and the
      treatment of adverse events. A cost-minimisation analysis was used; this assumes
      that the treatments are of equal efficacy, although direct randomised controlled
      trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil
      schedules were not available. The cost-minimisation analysis showed that
      treatment costs for a 12-week course of capecitabine (Pounds 2132) and tegafur
      with uracil (Pounds 3385) were lower than costs for the intravenous Mayo regimen
      (Pounds 3593) and infusional regimens on the de Gramont (Pounds 6255) and
      Modified de Gramont (Pounds 3485) schedules over the same treatment period. Oral
      therapies result in lower costs to the health service than intravenous therapies.
      Further research is needed to determine the relative clinical effectiveness of
      oral therapies vs infusional regimens.

PMID- 16804527
TI  - Regional localisation of p53-independent apoptosis determines toxicity to 5
      fluorouracil and pyrrolidinedithiocarbamate in the murine gut.
AB  - Pyrrolidinedithiocarbamate (PDTC) enhanced the activity of 5-fluorouracil (5-FU)
      in a colorectal cancer xenograft model. Pyrrolidinedithiocarbamate also reduced
      gastrointestinal toxicity associated with 5-FU therapy in large but not small
      bowel. We sought to clarify the basis of this differential enteric toxicity.
      Apoptosis and mitosis were assessed on a cell positional basis in small and large
      intestinal crypts of p53 wild-type (+/+) and p53 null (-/-) mice 6, 12, 24, 36,
      48 and 72 h after the administration of high (200 mg kg(-1)) or low (40 mg kg(
      1)) dose 5-FU+/-250 mg kg(-1) PDTC. Regimens were chosen to model a single human
      dose and a weekly schedule. The effects of another antioxidant N-acetylcysteine
      (NAC) were also investigated. Large intestinal crypts affect apoptosis purely by
      p53-dependent mechanisms, whereas small intestinal crypts are able to initiate
      both p53-dependent and -independent pathways following treatment with 5-FU.
      Pyrrolidinedithiocarbamate and NAC antagonised p53-dependent but potentiated p53
      independent apoptotic activity. Consequently, the proportion of surviving
      clonogens increased in the large but not in the small intestine. Regional
      availability of p53-dependent and -independent apoptotic pathways in small and
      large intestine together with separate modulation of these pathways by
      antioxidants explains the different regional enterotoxicity following 5-FU
      therapy.

PMID- 16804528
TI  - Method validation and preliminary qualification of pharmacodynamic biomarkers
      employed to evaluate the clinical efficacy of an antisense compound (AEG35156)
      targeted to the X-linked inhibitor of apoptosis protein XIAP.
AB  - Data are presented on pharmacodynamic (PD) method validation and preliminary
      clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates
      different forms of circulating cytokeratin 18 (CK18) as putative surrogate
      markers of both apoptotic and nonapoptotic tumour cell death, was shown to be
      highly reproducible: calibration curve linearity r2 = 0.996, mean accuracy > 91%
      and mean precision < 3%, n = 27. Employing recombinant (r) CK18 and caspase
      cleaved CK18 (CK18 Asp396 neo-epitope) as external standards, kit to kit
      reproducibly was < 6% (n = 19). rCK18 was stable in plasma for 4 months at -20
      degrees C and -80 degrees C, for 4 weeks at 4 degrees C and had a half-life of
      2.3 days at 37 degrees C. Cytokeratin 18 Asp396 NE, the M30 Apoptosense Elisa
      assay antigen, was stable in plasma for 6 months at -20 degrees C and -80 degrees
      C, for 3 months at 4 degrees C, while its half-life at 37 degrees C was 3.8 days.
      Within-day variations in endogenous plasma concentrations of the M30 and M65
      antigens were assessed in two predose blood samples collected from a cohort of 15
      ovarian cancer patients receiving carboplatin chemotherapy and were shown to be
      no greater than the variability associated with methods themselves. Between-day
      fluctuations in circulating levels of the M30 and M65 antigens and in XIAP mRNA
      levels measured in peripheral blood mononuclear cells by quantitative (q) RT-PCR
      were evaluated in two predose blood samples collected with a 5- to 7-day gap from
      23 patients with advanced cancer enrolled in a phase I trial. The mean variation
      between the two pretreatment values ranged from 13 to 14 to 25%, respectively,
      for M65, M30 and qRT-PCR. These data suggest that the M30 and M65 Elisa's and qRT
      PCR as PD biomarker assays have favourable performance characteristics for
      further investigation in clinical trials of anticancer agents which induce tumour
      apoptosis/necrosis or knockdown of the anti-apoptotic protein XIAP.

PMID- 16804529
TI  - Insulin-like growth factors and cancer: no role in screening. Evidence from the
      BUPA study and meta-analysis of prospective epidemiological studies.
AB  - Insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), and
      insulin-like growth factor binding protein-3 (IGFBP-3) were measured in frozen
      serum samples from 1051 men with cancer and 3142 controls in a nested case
      control study from the British United Provident Association (BUPA) study cohort
      and associations with 14 cancers were examined, including prostate, colorectal,
      and lung. A meta-analysis of studies on these three cancer sites was also
      conducted. In the meta-analysis the odds ratio between the highest quartile IGF-1
      group and the lowest quartile group was 1.31 (95% confidence interval (CI): 1.03
      1.67) for prostate, 1.37 (1.05-1.78) for colorectal and 1.02 (0.80-1.31) for lung
      cancer, and for IGF-2 it was 0.72 (0.36-1.44) for prostate and 1.95 (1.26-3.00)
      for colorectal cancer. Results from the BUPA study were consistent with the
      estimates from the other studies. There were no statistically significant
      associations with IGFBP-3 and any of the cancer sites considered. Our results
      suggest that IGF-1, IGF-2, and IGFBP-3 measurements have no value in cancer
      screening, although IGF-1 and IGF-2 may be of aetiological significance in
      relation to colorectal and prostate cancer.

PMID- 16804530
TI  - Concerning mobile phone use and risk of acoustic neuroma.

PMID- 16804531
TI  - Money troubles.

PMID- 16804532
TI  - Statistical false positive or true disease pathway?
AB  - Three very recent reports provide convincing statistical evidence (P < 10(-8)),
      at a genome-wide level, of the association of common polymorphisms with three
      different common diseases: systemic lupus erythematosus (IRF5), prostate cancer
      and type 1 diabetes (IFIH1 region). This adds to the trickle--soon to be a flood-
      of disease association results that are highly unlikely to be false positives.
      There are other convincing examples in the last 12 months: age-related macular
      degeneration (CFH), type 1 diabetes (IL2RA, also known as CD25) and type 2
      diabetes (TCF7L2). Given 20 years of a literature full of irreproducible results,
      what has changed?

PMID- 16804534
TI  - Mapping a plant's chemical vocabulary.

PMID- 16804535
TI  - CIMPle origin for promoter hypermethylation in colorectal cancer?

PMID- 16804536
TI  - Monkey see, monkey do.

PMID- 16804537
TI  - GATA1s goes germline.

PMID- 16804538
TI  - If it's not one thing, it's another.

PMID- 16804541
TI  - Bidirectional expression of CUG and CAG expansion transcripts and intranuclear
      polyglutamine inclusions in spinocerebellar ataxia type 8.
AB  - We previously reported that a (CTG)n expansion causes spinocerebellar ataxia type
      8 (SCA8), a slowly progressive ataxia with reduced penetrance. We now report a
      transgenic mouse model in which the full-length human SCA8 mutation is
      transcribed using its endogenous promoter. (CTG)116 expansion, but not (CTG)11
      control lines, develop a progressive neurological phenotype with in vivo imaging
      showing reduced cerebellar-cortical inhibition. 1C2-positive intranuclear
      inclusions in cerebellar Purkinje and brainstem neurons in SCA8 expansion mice
      and human SCA8 autopsy tissue result from translation of a polyglutamine protein,
      encoded on a previously unidentified antiparallel transcript (ataxin 8, ATXN8)
      spanning the repeat in the CAG direction. The neurological phenotype in SCA8 BAC
      expansion but not BAC control lines demonstrates the pathogenicity of the (CTG
      CAG)n expansion. Moreover, the expression of noncoding (CUG)n expansion
      transcripts (ataxin 8 opposite strand, ATXN8OS) and the discovery of intranuclear
      polyglutamine inclusions suggests SCA8 pathogenesis involves toxic gain-of
      function mechanisms at both the protein and RNA levels.

PMID- 16804542
TI  - Mutations in the gene encoding pejvakin, a newly identified protein of the
      afferent auditory pathway, cause DFNB59 auditory neuropathy.
AB  - Auditory neuropathy is a particular type of hearing impairment in which neural
      transmission of the auditory signal is impaired, while cochlear outer hair cells
      remain functional. Here we report on DFNB59, a newly identified gene on
      chromosome 2q31.1-q31.3 mutated in four families segregating autosomal recessive
      auditory neuropathy. DFNB59 encodes pejvakin, a 352-residue protein. Pejvakin is
      a paralog of DFNA5, a protein of unknown function also involved in deafness. By
      immunohistofluorescence, pejvakin is detected in the cell bodies of neurons of
      the afferent auditory pathway. Furthermore, Dfnb59 knock-in mice, homozygous for
      the R183W variant identified in one DFNB59 family, show abnormal auditory
      brainstem responses indicative of neuronal dysfunction along the auditory
      pathway. Unlike previously described sensorineural deafness genes, all of which
      underlie cochlear cell pathologies, DFNB59 is the first human gene implicated in
      nonsyndromic deafness due to a neuronal defect.

PMID- 16804543
TI  - The multidrug-resistant human pathogen Clostridium difficile has a highly mobile,
      mosaic genome.
AB  - We determined the complete genome sequence of Clostridium difficile strain 630, a
      virulent and multidrug-resistant strain. Our analysis indicates that a large
      proportion (11%) of the genome consists of mobile genetic elements, mainly in the
      form of conjugative transposons. These mobile elements are putatively responsible
      for the acquisition by C. difficile of an extensive array of genes involved in
      antimicrobial resistance, virulence, host interaction and the production of
      surface structures. The metabolic capabilities encoded in the genome show
      multiple adaptations for survival and growth within the gut environment. The
      extreme genome variability was confirmed by whole-genome microarray analysis; it
      may reflect the organism's niche in the gut and should provide information on the
      evolution of virulence in this organism.

PMID- 16804544
TI  - CpG island methylator phenotype underlies sporadic microsatellite instability and
      is tightly associated with BRAF mutation in colorectal cancer.
AB  - Aberrant DNA methylation of CpG islands has been widely observed in human
      colorectal tumors and is associated with gene silencing when it occurs in
      promoter areas. A subset of colorectal tumors has an exceptionally high frequency
      of methylation of some CpG islands, leading to the suggestion of a distinct trait
      referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the
      existence of CIMP has been challenged. To resolve this continuing controversy, we
      conducted a systematic, stepwise screen of 195 CpG island methylation markers
      using MethyLight technology, involving 295 primary human colorectal tumors and
      16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors
      convincingly represent a distinct subset, encompassing almost all cases of tumors
      with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair
      deficiency occur almost exclusively as a consequence of CIMP-associated
      methylation of MLH1 . We propose a robust new marker panel to classify CIMP+
      tumors.

PMID- 16804548
TI  - APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.
AB  - Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein
      in the brain and plays an important role in modulating the outcome and
      regenerative processes after acute brain injury. The aim of the present study was
      to determine if gene transfer of the epsilon3 form of APOE improves outcome in a
      murine model of transient focal cerebral ischaemia. Mice received an
      intrastriatal injection of vehicle, a second-generation adenoviral vector
      containing the green fluorescent protein gene (Ad-GFP) or a vector containing the
      APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green
      fluorescent protein expression was observed in cells throughout the striatum and
      subcortical white matter indicating successful gene transfer and expression. ApoE
      levels in the brain were significantly increased after Ad-APOE compared with Ad
      GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic
      damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4
      versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was
      enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results
      show the ability of APOE gene transfer to markedly improve outcome after cerebral
      ischaemia and suggest that modulating apoE levels may be a potential strategy in
      human stroke therapy.

PMID- 16804549
TI  - Reduced cerebral blood flow but elevated cerebral glucose metabolic rate in
      erythropoietin overexpressing transgenic mice with excessive erythrocytosis.
AB  - To examine the impact of excessive erythrocytosis on local cerebral blood flow
      (CBF) and cerebral glucose metabolic rate (CMR(glc)), we made use of our
      constitutively erythropoietin (Epo)-overexpressing transgenic mouse line (tg-6)
      that reach a mean hematocrit of 0.87. Compared with wild-type (wt) control
      siblings, CBF decreased by 44% in tg-6 mice, while upon hemodilution (tg-6-HD) to
      a physiologic hematocrit (e.g., 0.44) tg-6-HD mice returned the CBF to wt levels.
      Cerebral blood flow was determined in another transgenic mouse line that
      overexpresses human Epo in the brain only (tg-21): CBF increased by 17% compared
      with wt controls. However, oxygen delivery was similar in all four mouse groups
      tested (wt, tg-6, tg-6-HD and tg-21). Mean CMR(glc) was higher in tg-6 (+72%), tg
      6-HD mice (+43%) and tg-21 (+22%) than in wt mice. Local CMR(glc) was higher in
      all 40 brain regions in tg-6 but only in 15 and 8 regions in tg-6-HD and tg-21
      mice. These results show that prolonged increases in hematocrit did not alter
      cerebral oxygen delivery at a decreased CBF and increased CMR(glc). Hemodilution
      suggests that high blood viscosity is a cause of the decrease in CBF and partly
      of the increase in CMR(glc). Cerebral glucose metabolic rate may also be
      increased by a direct effect of Epo in the brain (tg-21 mice).

PMID- 16804550
TI  - Abnormal metabolic network activity in Parkinson's disease: test-retest
      reproducibility.
AB  - Parkinson's disease (PD) is associated with an abnormal pattern of regional brain
      function. The expression of this PD-related covariance pattern (PDRP) has been
      used to assess disease progression and the response to treatment. In this study,
      we validated the PDRP network as a measure of parkinsonism by prospectively
      computing its expression (PDRP scores) in (15)O-water (H(2)(15)O) and (18)F
      fluorodeoxyglucose (FDG) positron emission tomography (PET) scans from PD
      patients and healthy volunteers. The reliability of this measure was also
      assessed within subjects using a test-retest design in mildly affected and
      advanced PD patients scanned at baseline and during treatment with levodopa or
      deep brain stimulation (DBS). We found that PDRP expression was significantly
      elevated in PD patients (P<0.001) relative to controls in a prospective analysis
      of brain scans obtained with either H(2)(15)O or FDG PET. A significant
      correlation (R(2)=0.61; P<0.001) was evident between PDRP scores computed from
      H(2)(15)O and FDG images in PD subjects scanned with both tracers. Test-retest
      reproducibility was very high (intraclass correlation coefficient (ICC)>0.92) for
      PDRP scores measured both within PET session and between sessions separated by up
      to 2 months. This high reproducibility was observed in both early stage and
      advanced PD patients scanned at baseline and during treatment. The within-subject
      variability of this measure was less than 10% for both unmedicated and treated
      conditions. These findings suggest that the PDRP network is a reproducible and
      stable descriptor of regional functional abnormalities in parkinsonism. The
      quantification of PDRP expression in PD patients can serve as a potential
      biomarker in PET intervention studies for this disorder.

PMID- 16804551
TI  - Theoretical and experimental optimization of laser speckle contrast imaging for
      high specificity to brain microcirculation.
AB  - The functional spatial resolution in most of hemodynamics-based functional
      neuroimaging techniques is limited by the fineness of hemodynamic control with
      the active vascular beds likely at submillimeter resolution. This study was
      designed to visualize changes of cerebral blood flow (CBF) at submillimeter
      spatial scale on the prolonged isoflurane-anesthetized rats model by using laser
      speckle contrast imaging (LSCI) technique. Recently, this old method has
      attracted an increasing interest in studies of brain activities under normal and
      pathophysiologic conditions. However, some paramount assumptions behind this
      imaging technique have been kept ignored in this field since 1981 firstly
      proposed by Fercher and Briers. Most recently, these assumptions are claimed as
      serious mistakes that made LSCI fail to reproducibly and correctly measure blood
      flow speed. In our study, these issues are also re-examined theoretically and re
      evaluated experimentally based on the results from the classical carbon dioxide
      challenge model. The detailed distribution of CBF responses to the stimulation
      induced by different levels of carbon dioxide pressure was obtained with tens of
      micron spatial resolution. The relative CBF images over the exposed cortical area
      acquired by LSCI were also compared with laser-Doppler measurements. Our results
      show that these assumptions would not produce any significant errors on
      investigating changes of blood flow and also achieve high specificity to assess
      cerebral microcirculation, as would facilitate its broad application in
      functional imaging field.

PMID- 16804552
TI  - Hyperglycemia in acute ischemic stroke: a vascular perspective.
AB  - Admission hyperglycemia complicates approximately one-third of acute ischemic
      strokes and is associated with a worse clinical outcome. Both human and animal
      studies have showed that hyperglycemia is particularly detrimental in
      ischemia/reperfusion. Decreased reperfusion blood flow has been observed after
      middle cerebral artery occlusion in acutely hyperglycemic animals, suggesting the
      vasculature as an important site of hyperglycemic reperfusion injury. This paper
      reviews biochemical and molecular pathways in the vasculature that are rapidly
      affected by hyperglycemia and concludes that these changes result in a pro
      vasoconstrictive, pro-thrombotic and pro-inflammatory phenotype that renders the
      vasculature vulnerable to reperfusion injury. Understanding these pathways should
      lead to the development of rational therapies that reduce hyperglycemic
      reperfusion injury and thus improve outcome in this large subset of acute
      ischemic stroke patients.

PMID- 16804553
TI  - Population genetics: separating nurture from nature in estimating heritability.

PMID- 16804554
TI  - The value of gene-based selection of tag SNPs in genome-wide association studies.
AB  - Genome-wide association scans are rapidly becoming reality, but there is no
      present consensus regarding genotyping strategies to optimise the discovery of
      true genetic risk factors. For a given investment in genotyping, should tag SNPs
      be selected in a gene-centric manner, or instead, should coverage be optimised
      based on linkage disequilibrium alone? We explored this question using empirical
      data from the HapMap-ENCODE project, and we found that tags designed specifically
      to capture common variation in exonic and evolutionarily conserved regions
      provide good coverage for 15-30% of the total common variation (depending on the
      population sample studied), and yield genotype savings compared with an anonymous
      tagging approach that captures all common variation. However, the same number of
      tags based on linkage disequilibrium alone captures substantially more (30-46%)
      of the total common variation. Therefore, the best strategy depends crucially on
      the unknown degree to which functional variation resides in recognisable exons
      and evolutionarily conserved sequence. A hypothetical but reasonable scenario
      might be one in which trait-causing variation is equally distributed between
      exons plus conserved sequence, and the rest of the genome. In this scenario, our
      analysis suggests that a tagging approach that captures variation in exons and
      conserved sequence provides only modestly better coverage of putatively causal
      variation than does anonymous tagging. In HapMap CEU samples (with northern and
      western European ancestry), we observed roughly equivalent coverage for equal
      investment for both tagging strategies.

PMID- 16804556
TI  - Polyphenol-enriched oolong tea increases fecal lipid excretion.
AB  - OBJECTIVE: To assess possibility of polyphenol-enriched oolong tea to reduce
      dietary lipid absorption in humans. DESIGN: Twelve healthy adult subjects, three
      males and nine females, aged (mean+/-s.d.) 22.0+/-1.8 years, respectively, were
      randomly divided into two groups. The participants were followed a double-blind
      placebo-controlled crossover design, including 7-day washout periods and 10-day
      treatment periods. During the treatment periods, subjects were given about 38 g
      of lipids from potato chips (19 g each within 30 min after lunch and dinner) and
      total 750 ml beverages (placebo- or polyphenol-enriched oolong tea) at three
      meals. Blood samples were collected for biochemical examination at days 8, 18, 25
      and 35 of the study period. On the last 3 days of each treatment period, feces
      were collected to measure the excretion of lipids. RESULTS: Lipid excretion into
      feces was significantly higher in the polyphenol-enriched oolong tea period
      (19.3+/-12.9 g/3 day) than in the placebo period (9.4+/-7.3 g/3 day) (P < 0.01).
      Cholesterol excretion tended to increase in polyphenol-enriched oolong tea period
      (1.8+/-1.2 g/3 day) compared with that of placebo (1.2+/-0.6 g/3 day) (P =
      0.056). CONCLUSIONS: The results of this study indicated that polyphenol-enriched
      oolong tea could increase lipid excretion into feces when subjects took high
      lipid diet.

PMID- 16804555
TI  - Dietary patterns in the Southampton Women's Survey.
AB  - OBJECTIVE: Dietary pattern analysis is receiving increasing attention as a means
      of summarizing the multidimensional nature of dietary data. This research aims to
      compare principal component analysis (PCA) and cluster analysis using dietary
      data collected from young women in the UK. DESIGN: Diet was assessed using a 100
      item interviewer-administered food frequency questionnaire. PCA and cluster
      analysis were used to examine dietary patterns. SETTING: Southampton, UK.
      SUBJECTS: A total of 6125 non-pregnant women aged 20-34 years. RESULTS: PCA
      identified two important patterns: a 'prudent' diet and a 'high-energy' diet.
      Cluster analysis defined two clusters, a 'more healthy' and a 'less healthy'
      cluster. There was a strong association between the prudent diet score and the
      two clusters, such that the mean prudent diet score in the less healthy cluster
      was -0.73 standard deviations and in the more healthy cluster was +0.83 standard
      deviations; the difference in the high-energy diet score between the two clusters
      was considerably smaller. CONCLUSIONS: Both approaches revealed a similar dietary
      pattern. The continuous nature of the outcome of PCA was considered to be
      advantageous compared with the dichotomy identified using cluster analysis.
      SPONSORSHIP: The study was funded by the Dunhill Medical Trust, the University of
      Southampton and the Medical Research Council.

PMID- 16804557
TI  - Comparison of resting energy expenditure in bronchopulmonary dysplasia to
      predicted equation.
AB  - OBJECTIVE: Children with bronchopulmonary dysplasia (BPD) often suffer from
      growth failure because of disturbances in energy balance with an increase of
      resting energy expenditure (REE). Evaluation of REE is a useful tool for
      nutritional management. Indirect calorimetry is an elective method for measuring
      REE, but it is time consuming and requires rigorous procedure. The objective of
      this study was to test accuracy of prediction equation to evaluate REE in BPD
      children. PATIENTS AND METHODS: Fifty-two children aged 4-10 years with BPD (30
      boys and 22 girls) and 30 healthy lean children (20 boys and 10 girls) were
      enrolled. In this study, indirect calorimetry was compared to four prediction
      equations (Schoffield-W, Schoffield-HW, Harris-Benedict and Food and Agriculture
      Organization equation) using Bland-Altman pair wise comparison. RESULTS: The
      Harris-Benedict equation was the best equation to predict REE in children with
      BPD, and Schoffield-W was the best in healthy children. For the children with
      chronic lung disease of prematurity the Harris-Benedict equation showed the
      lowest mean predicted REE-REE measured by indirect calorimetry difference
      (difference = 15 kcal/day; limits of agreement -266 and 236 kcal/day; 95%
      confidence interval for the bias -207 to 177 kcal/day), and graphically, the best
      agreement. For the group of healthy children, it was the Schofield-W equation (
      2.9 kcal/day; limits of agreement -275 and 269 kcal/day; 95% confidence interval
      for the bias -171 to 165 kcal/day), and graphically, the best agreement.
      CONCLUSION: Differences in prediction equation are minimal compared to
      calorimetry. Prediction equation could be useful in the management of children
      with BPD.

PMID- 16804558
TI  - Evaluation of external radiation dosimetry records at the Savannah River Site,
      1951-1989.
AB  - The Savannah River Site (SRS) is one of the largest facilities in the nation's
      nuclear weapons complex. To date, little information has been published regarding
      radiation risk estimates derived from epidemiological studies of SRS workers. As
      part of an ongoing epidemiological cohort study of SRS workers, we have assessed
      the suitability of the Site's personnel radiation dosimetry information for use
      in epidemiological analyses. This paper provides information on historical
      dosimetry methods, recording practices, and the completeness of computerized
      dosimetry information for workers employed at SRS during the period 1951-1989,
      when the site was operated by the du Pont Company. The study includes 18,883
      workers hired at SRS between 1951 and 1987 who were employed for at least 90
      days. Documents relating to external radiation dosimetry methods were reviewed,
      recorded doses were examined to evaluate recording practices, and the
      completeness of monitoring was assessed by comparing employment history and
      computerized dosimetry records, and by implementing a "nearby" procedure for
      estimating values for missing annual dosimetry records. Dosimeter technology
      evolved over this period from two-element film dosimeters to multielement
      thermoluminescent dosimeters. Dosimetry measurements were recorded consistently
      in 0.05 millisievert (mSv) increments. Prior to 1973, recording thresholds of
      0.10-0.15 mSv were used while from 1973 to 1989 a recording threshold of 0.05 mSv
      was used. We abstracted nearly 3 person-Sv of dosimetry information that was
      available in hardcopy but not in computerized format. The collective dose from
      the computerized and abstracted records totaled 512.1 person-Sv. A "nearby"
      method was used to estimate dose values for 13,812 employment-years for which
      dosimetry information was not available. The average estimated value was 0.6 mSv
      and the assigned collective dose derived via the "nearby" procedure was 8.7
      person-Sv. The consistency of dosimetry practices at SRS and the completeness of
      historical dosimetry records are supportive of their use in epidemiologic
      research.

PMID- 16804559
TI  - An evaluation of the indoor air quality in bars before and after a smoking ban in
      Austin, Texas.
AB  - This study assessed differences in the indoor air quality and occupancy levels in
      seventeen bars due to a city-wide smoking ban that took effect on September 1,
      2005 in Austin, Texas, USA. We measured the following in each venue before and
      after the smoking ban: mean number of occupants, mean number of lit cigarettes,
      temperature, relative humidity, room volume, and PM(2.5), CO, and CO(2)
      concentrations. Additionally, VOC measurements were conducted at three of the
      venues. There was not a statistically significant change in occupancy, but the
      best estimate PM(2.5) concentrations in the venues decreased 71-99%, a
      significant reduction in all venues, relative to the pre-ban levels; CO
      concentrations decreased significantly in all but one venue; and concentrations
      of VOCs known to be emitted from cigarettes decreased to below the detection
      limit for all but two common compounds. These results suggest that the smoking
      ban has effectively improved indoor air quality in Austin bars without an
      associated decrease in occupancy.

PMID- 16804560
TI  - Costs of Caregiving: Weight Loss in Captive Adult Male Cotton-Top Tamarins
      (Saguinus oedipus) Following the Birth of Infants.
AB  - We examined changes in weight for 10 captive adult male cotton-top tamarins
      (Saguinus oedipus) from before the birth of infants through the first 16 weeks of
      infant life. Compared to before birth, males weighed significantly less in Weeks
      1-4, 5-8, and 9-12 following the birth. Weights in Weeks 13-16 did not differ
      significantly from prebirth weights. Maximum weight loss for individual males
      ranged from 1.3 to 10.8% of prebirth body weight. Males in groups with fewer
      helpers lost significantly more weight than ones in groups with more helpers. For
      the 3 males that had no helper other than their mates, weight loss was
      particularly striking, ranging from 10.0 to 10.8% of their prebirth body weight.
      These results suggest that caring for infants is energetically costly, and that
      in this cooperatively breeding species, the presence of more individuals to share
      the burden of infant carrying reduces the cost to individual caregivers.

PMID- 16804561
TI  - Cooperative problem solving in a cooperatively breeding primate (Saguinus
      oedipus).
AB  - We investigated cooperative problem solving in unrelated pairs of the
      cooperatively breeding cottontop tamarin, Saguinus oedipus, to assess the
      cognitive basis of cooperative behaviour in this species and to compare abilities
      with other apes and monkeys. A transparent apparatus was used that required
      extension of two handles at opposite ends of the apparatus for access to rewards.
      Resistance was applied to both handles so that two tamarins had to act
      simultaneously in order to receive rewards. In contrast to several previous
      studies of cooperation, both tamarins received rewards as a result of
      simultaneous pulling. The results from two experiments indicated that the
      cottontop tamarins (1) had a much higher success rate and efficiency of pulling
      than many of the other species previously studied, (2) adjusted pulling behaviour
      to the presence or absence of a partner, and (3) spontaneously developed
      sustained pulling techniques to solve the task. These findings suggest that
      cottontop tamarins understand the role of the partner in this cooperative task, a
      cognitive ability widely ascribed only to great apes. The cooperative social
      system of tamarins, the intuitive design of the apparatus, and the provision of
      rewards to both participants may explain the performance of the tamarins.

PMID- 16804562
TI  - Alcohol abuse prevention among high-risk youth: computer-based intervention.
AB  - SUMMARYThis study examined the feasibility of a CD-ROM intervention to prevent
      alcohol abuse among high-risk youths. Youths from 41 community-based agencies in
      greater New York City participated in a randomized trial of a skills-based
      interactive CD-ROM. Outcome data were collected on 489 early adolescents in these
      agencies before and after a randomized subset of youths interacted with a 10
      session alcohol abuse prevention program on CD-ROM. Compared to control
      participants, youths in the intervention arm had a positive increase in perceived
      harm of alcohol use and increased assertiveness skills. At posttest, drinking
      rates for control and intervention participants were equal and unchanged from
      pretest. These findings suggest that CD-ROM technology offers a new and promising
      medium for engaging high-risk youth in an alcohol abuse prevention program. Study
      implications and future applications of the present approach are discussed.

PMID- 16804564
TI  - The discovery and role of CD147 as a subunit of gamma-secretase complex.
AB  - Gamma-secretase is a membrane protein complex with unusual aspartyl protease
      activity that cleaves a variety of type I transmembrane proteins, such as APP,
      Notch and E-cadherin, within their transmembranous regions. Gamma-secretase was
      first recognized because of its role in the production of Abeta peptides that are
      pathogenic in Alzheimer's disease. There is overwhelming evidence demonstrating
      that four components, presenilin, nicastrin, APH-1 and PEN-2, are necessary and
      sufficient for gamma-secretase activity. However, based on the findings of
      studies conducted on cells overexpressing these four components, the existence of
      regulatory components of the gamma-secretase complex has been postulated.
      Recently, an additional subunit of the gamma-secretase complex, membrane protein
      CD147, has been identified through the purification and characterization of
      endogenous complexes from HeLa cell membranes. Removal of CD147 from gamma
      secretase complexes increases the production of Abeta-peptides. Elucidating the
      molecular mechanism by which CD147 exerts its effect on the activity of the gamma
      secretase complex will help us to further understand the pathogenesis of
      Alzheimer's disease, and may allow for the development of novel therapeutics.

PMID- 16804563
TI  - Downregulation of uPA, uPAR and MMP-9 using small, interfering, hairpin RNA
      (siRNA) inhibits glioma cell invasion, angiogenesis and tumor growth.
AB  - The diffuse, extensive infiltration of malignant gliomas into the surrounding
      normal brain is believed to rely on modification of the proteolysis of
      extracellular matrix components. Our previous results clearly demonstrate that
      uPA, uPAR and MMP-9 concentrations increase significantly during tumor
      progression and that tumor growth can be inhibited with antisense stable clones
      of these molecules. Because antisense-mediated gene silencing does not completely
      inhibit the translation of target mRNA and high concentrations of antisense
      molecules are required to achieve gene silencing, we used the RNAi approach to
      silence uPA, uPAR and MMP-9 in this study. We examined a cytomegalovirus (CMV)
      promoter-driven DNA-template approach to induce hairpin RNA (hpRNA)-triggered
      RNAi to inhibit uPA, uPAR and MMP-9 gene expression with a single construct. uPAR
      protein levels and enzymatic activity of uPA and MMP-9 were found to
      significantly decrease in cells transfected with a plasmid expressing hairpin
      siRNA for uPAR, uPA and MMP-9. pU(2)M-transfected SNB19 cells significantly
      decreased uPA, uPAR and MMP-9 expression compared to mock and EV/SV-transfected
      cells, determined by immunohistochemical analysis. Furthermore, the effect of the
      single constructs for these molecules was a specific inhibition of their
      respective protein levels, as demonstrated by immunohistochemical analysis. After
      transfection with a plasmid vector expressing dsRNA for uPA, uPAR and MMP-9,
      glioma-cell invasion was retarded compared with mock and EV/SV-treated groups,
      demonstrated by Matrigel-invasion assay and spheroid-invasion assay.
      Downregulation of uPA, uPAR and MMP-9 using RNAi inhibited angiogenesis in an in
      vitro (co-culture) model. Direct intratumoral injections of plasmid DNA
      expressing hpRNA for uPA, uPAR and MMP-9 significantly regressed pre-established
      intracranial tumors in nude mice. In addition, cells treated with RNAi for uPAR,
      uPA and MMP-9 showed reduced pERK levels compared with parental and EV/SV-treated
      SNB19 cells. Our results support the therapeutic potential of RNAi as a method
      for gene therapy in treating gliomas.

PMID- 16804565
TI  - Vacuolar ATPase as a drug discovery target.
AB  - Vacuolar ATPases (V-ATPases) are present not only in the plasma membranes of
      specialized cells but also in ubiquitous intracellular acidic compartments, which
      are essential for physiological cellular function. Consequently, although V
      ATPases are important etiologically in several diseases, it seems that they might
      not be good molecular targets. In fact, bafilomycin A1, a potent and specific
      inhibitor of V-ATPase, exerts severe and acute toxic reaction when administered
      to animals. On the other hand, disruption of subunit a3 of V-ATPase is not
      embryonic lethal, but knockout mice merely exhibit osteopetrosis due to loss of
      osteoclastic bone resorption. In addition, recent studies have demonstrated that
      novel V-ATPase inhibitors, which have inhibition selectivity, can be systemically
      administered to animals and are highly efficacious against bone loss in lytic
      bone disease models. Therefore, the key issue regarding the therapeutic
      usefulness of V-ATPase inhibitors is their selectivity in the inhibition.

PMID- 16804566
TI  - NAAG peptidase as a therapeutic target: Potential for regulating the link between
      glucose metabolism and cognition.
AB  - There is a new class of CNS drugs, N-acetylaspartylglutamate (NAAG) peptidase
      inhibitors, that can affect a two-step, neuron-astrocyte/astrocyte-vascular
      endothelium, signaling mechanism. Using this homeostatic mechanism, activated
      neurons continuously interact with the vascular system to indicate ongoing
      requirements for supplies of glucose (Glc) and oxygen needed to maintain
      cognitive functions. These new drugs impact the first step by inhibiting NAAG
      peptidase, located on the astrocyte surface, that cleaves glutamate (Glu) from
      the neuropeptide NAAG after it has docked with the astrocyte surface metabotropic
      Glu receptor 3 (mGluR3). As a result, this interferes with initiation of the
      second step, the astrocyte-vascular endothelium signal, activation of which
      results in a rapid hyperemic response that increases focal availability of energy
      supplies. Since NAAG is liberated upon each neuron depolarization, its release is
      linked to the level of neuronal spiking. This insures that its mGluR3 signal
      function reflects current levels of neuronal stimulation, so that Glc and oxygen
      can be supplied in a timely manner for metabolic replacement of ATP stocks
      depleted during the repolarization process. The metabolism of NAAG is very
      complex, being a component of the only metabolic sequence in the brain requiring
      three major brain cell types--neurons, astrocytes and oligodendrocytes--for its
      successful completion. In this review, we describe the unique NAAG tricellular
      metabolic cycle and survey some reported actions of these new and novel drugs. We
      also consider their probable site and mode of action and speculate upon their
      therapeutic potential.

PMID- 16804568
TI  - Molecule of the Month. Varenicline tartrate.

PMID- 16804567
TI  - Trabecular meshwork as a new target for the treatment of glaucoma.
AB  - Glaucoma, a group of optic neuropathies, is one of the leading causes of
      irreversible blindness in the world. It is characterized by degeneration of the
      optic nerve and progressive visual field loss, often associated with elevated
      intraocular pressure (IOP). In primary open-angle glaucoma, the most common form
      of the disease, IOP occurs as a result of abnormally increased resistance to
      drainage of aqueous humor through the conventional outflow system, which
      comprises the trabecular meshwork and the Schlemm's canal. The pharmacological
      treatment of glaucoma has been classically aimed at lowering elevated IOP, either
      decreasing the production of aqueous humor or improving its outflow. Increasing
      knowledge of trabecular meshwork physiology shows that this tissue has unique
      morphologic and functional properties involved in the regulation of aqueous humor
      outflow. Although trabecular meshwork physiology is yet to be fully revealed, ion
      channels involved in cell contractility or cell volume regulation, or those
      capable of responding to high pressure, have been described and may be considered
      promising pharmacological targets for the treatment of glaucoma. The cytoskeleton
      architecture of the trabecular meshwork cell is thought to be an important
      regulator of aqueous humor outflow. Gene technology directed at discovering genes
      linked to the development of glaucoma or to those upregulated in response to
      elevated IOP is challenging research but provides an insight into future gene
      therapy. New tools to study trabecular meshwork physiology have recently been
      developed, including the use of lentivirus for gene delivery or fusion proteins
      with a protein transduction domain. These vectors are targeted specifically to
      the trabecular meshwork and are powerful techniques with broad applications for
      future gene therapy or as new forms of drug delivery.

PMID- 16804569
TI  - Glycomics: From glycobiology to diagnostics and therapeutics.
AB  - The Royal Society of Chemistry Biotechnology Group and Chemical Biology Forum
      held a two-day symposium on December 12-13, 2005, in London. The meeting was
      designed to give an overview of the exciting new technologies being applied to
      study complex carbohydrates from their sequence analysis, characterization and
      function through to the development of novel pharmacological approaches to
      diagnose and alleviate polysaccharide-mediated diseases. The meeting, which also
      included a poster session, highlighted the multidisciplinary nature of the
      research and development and the exciting advances being made in this field.

PMID- 16804570
TI  - Latest advances and research in stroke: Focus on diagnostic and therapeutic
      targets.
AB  - The 31st International Stroke Conference, held February 16-18, 2006, in
      Kissimmee, Florida, U.S.A., highlighted more than 550 presentations emphasizing
      basic and translational sciences and explored how these sciences evolve to unlock
      our understanding of stroke pathophysiology with the aim of developing more
      effective prevention diagnosis and treatment tools. This year's conference
      reached record attendance, with more than 4,000 participants. In this report we
      will focus on new diagnostic and therapeutic stroke targets addressed in the
      meeting, together with the trends in neurovascular research presented at the oral
      and poster sessions of this two-and-a-half day congress.

PMID- 16804573
TI  - Handles for the dicarbadodecaborane basket based on [arachno-5,10-C2B8H13]-:
      oxygen.
AB  - A unique novel oxacarbaborane was prepared by a controlled attack of closo-1,2
      C2B8H10 on Bu4NOH and its molecular geometry was derived on the basis of the well
      established ab initio/GIAO/NMR method, GIAO-MP2/II//MP2/6-31G* and experimental
      11B chemical shifts showing an excellent agreement.

PMID- 16804571
TI  - Surgical management of valvular heart disease 2004.

PMID- 16804574
TI  - Molecular dynamics simulations of hydration, dissolution and nucleation processes
      at the alpha-quartz (0001) surface in liquid water.
AB  - Molecular dynamics simulations have been employed to investigate the hydration
      and dissolution of alpha-quartz (0001) surfaces in a liquid water environment.
      Our study indicates that the structure of the water layers near the surfaces is
      affected by the nature of the substrate surface and by temperature. Ordered mono
      layers of interfacial water molecules form in the region of the substrate where
      the surface is highly charged and built up of Si-O-Si bridges. As the temperature
      is increased this ordered mono-layer structure is gradually lost. When the
      surface is terminated by silanol groups, the water retains liquid-like properties
      even at low temperature and the molecules are distributed in a random manner,
      without the formation of distinct ordered mono-layers of water molecules near the
      surface. Taking into account the entropy of the system, the calculated energies
      of stepwise dissolution of a silicon species from the surface suggest that on
      thermodynamic grounds the complete dissolution of silicon atoms from the quartz
      surfaces in a liquid water environment is an endothermic process, but that the
      formation of a -Si(OH)3 species at the surface would be possible. In addition, if
      the Si(OH)(4) species were to be dissolved, it would remain near the surface, and
      re-deposition at the defect-free surface is thermodynamically preferred, although
      there is an activation enthalpy to the first step in the process of nucleation of
      Si(OH)4 at the perfect surface.

PMID- 16804572
TI  - A positively charged trinuclear 3N-chelated monofunctional platinum complex with
      high DNA affinity and potent cytotoxicity.
AB  - A trinuclear 3N-chelated monofunctional platinum complex, [Pt3(HPTAB)Cl3](ClO4)3
      (HPTAB = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5
      tris(aminomethyl)benzene), has been structurally characterized, which binds to
      DNA and demonstrates much higher potency against the murine leukemia cell line (P
      388) and the human nonsmall-cell lung cancer cell line (A-549) than cisplatin.

PMID- 16804575
TI  - Aggregation of imine-based metallo-supramolecular architectures through pi-pi
      interactions.
AB  - The design of supramolecular architectures based on isoquinoline-imine ligand
      systems is described. The isoquinoline affords an extended pi surface and the use
      of this surface to obtain self-recognition and consequent pi-pi aggregation is
      investigated. The approach is effective in that each of four complexes is
      observed to aggregate through these interactions. Other pi-pi interactions can
      interfere with the aggregation indicating that a larger pi-surface may be
      required to obtain complete control over the aggregation of the units.

PMID- 16804576
TI  - Theoretical study of the exchange coupling in a Ni12 single-molecule magnet.
AB  - The exchange interactions in a Ni12 complex have been studied by using
      theoretical methods based on density functional theory. The calculated J values
      reproduce correctly the S = 12 ground state of this system found experimentally
      and indicate the presence of three different exchange interaction pathways, in
      agreement with previous inelastic neutron scattering experiments. The three
      interactions are ferromagnetic, one of them corresponding to a second-neighbor
      interaction through a syn-anti acetato ligand. A magnetostructural correlation
      was found for such coupling, confirming the ferromagnetic nature of such an
      interaction. Our results are in excellent agreement with two new fittings of the
      experimental magnetic susceptibility data. The spin density distribution of the
      Ni12 complex is also reported and discussed.

PMID- 16804577
TI  - Encapsulation of labile trivalent lanthanides into a homobimetallic chromium(III)
      containing triple-stranded helicate. Synthesis, characterization, and divergent
      intramolecular energy transfers.
AB  - The segmental bidentate-tridentate-bidentate ligand L2 reacts with M(II) (M = Cr,
      Zn) and Ln(III) (Ln = La, Eu, Gd, Tb, Lu) to give the heterotrimetallic triple
      stranded helicates [MLnM(L2)3]7+. For M = Zn(II), the isolated complexes
      [ZnLnZn(L2)3](CF3SO3)7 (Ln = Eu, Tb) display only lanthanide-centred luminescence
      arising from the pseudo-tricapped trigonal prismatic LnN9 coordination site. For
      M = Cr(II), rapid air oxidation provides Cr(III) and leads to the isolation of
      inert [CrLnCr(L2)3](CF3SO3)9 (Ln = Eu, Tb) complexes, in which divergent
      intramolecular Ln --> Cr energy transfers can be evidenced. Taking
      [ZnEuZn(L2)3]7+ as a luminescent standard for Eu-centred emission, a quantitative
      treatment of the energy migration processes indicates that the rate constant
      characterizing the Eu --> Cr energy transfer is more efficient in the trimetallic
      system, than in the analogous simple bimetallic edifice. Particular attention is
      focused on potential control of directional energy transfer processes in Cr-Ln
      pairs.

PMID- 16804578
TI  - Use of the tetrahydroborate ligand as "gate-keeper" and protected hydride ligand:
      preparation and study of alkyl hydride and acyl hydride complexes of
      ruthenium(II).
AB  - Complex 3, [Ru(eta2-BH4)(CO)(Et)L2] (L = PMe2Ph) can be converted by nucleophiles
      L' {a, PMe2Ph; b, P(OMe)3; c, Me3CNC; d, CO} to alkyl and acyl complexes [Ru(eta1
      BH4)(CO)(Et)L2L'] (4a), [Ru(eta2-BH4)(COEt)L2L'] (5a-d), and [Ru(eta1
      BH4)(COEt)L2L'2] (7d and isomers 7c and 10c). Deprotection can then be achieved
      under conditions mild enough to allow study of the resulting alkyl hydride
      complexes [Ru(CO)(Et)HL2L'] (1a, 1b) and acyl hydride complexes [Ru(COEt)HL2L'2]
      (8c, 8d) prior to elimination of ethane and propanal respectively, with formation
      of ruthenium(0) complexes [Ru(CO)L2L'2] (6a, 6b, 6d). With Me3CNC, however, the
      final product is (depending on the solvent used) [Ru(CNCMe3)2{C(H)NCMe3}(COEt)L2]
      (9c) or [Ru(CNCMe3)3(COEt)L2]+ (11c). Successive treatment of [Ru(eta2
      BH4)(CO)HL2], , with ethene and then CO yields propanal, but turning this into a
      catalytic cycle is hindered by the greater readiness of to yield propanal non
      catalytically (reacting with CO) than catalytically (reacting with H2).

PMID- 16804579
TI  - Tuning "kappticity" of tripodal ligands.
AB  - The synthesis and structural characterization of a series of tripodal
      tris(phosphine) ligands, containing SiMe2 elbow groups, is described. The
      significant steric congestion in these ligands, due to the silylmethyl
      substituents, is manifest both in the solid-state structures and in the solution
      NMR spectra of the free ligands. Variable temperature 1H{31P} NMR studies of one
      of the ligands, CH3C(SiMe2PEt2)3 (4b) gave an estimated barrier to rotation
      around the Si-Capical bonds of approximately 10.4 kcal mol(-1). Octahedral kappa2
      and kappa3-molybdenum complexes of these ligands also demonstrate the impact of
      the additional bulk imparted by the SiMe2 substituents, and the high Lewis
      basicity of these phosphines, with subtle changes at the apical and phosphine
      substituents changing the overall coordination chemistry observed.

PMID- 16804580
TI  - A new titanium building block for early-late heterometallic complexes;
      preparation of a new tetrameric metallomacrocycle by self assembly.
AB  - The new titanium dicarboxylate complex Cp*TiMe(OOC)2py (2) [Cp*=eta5-C5Me5;
      (OOC)2py = 2,6-pyridinedicarboxylate] has been synthesized. The reaction of
      complex 2 with water renders [Cp*Ti(OOC)2py]2O (3). The molecular structure of 3
      has been studied by X-ray diffraction methods. Complex 2 reacts with isocyanides
      to yield the respective iminoacyl derivatives Cp*Ti(eta2-MeCNR)(OOC)2py [R=tBu
      (4), 2,6-dimethylphenyl (xylyl) (5)]. The molecular structure of complex4 has
      been established by X-ray diffraction. Compound 2 has been employed as a new
      building block for the preparation of new early-late heterometallic compounds; it
      reacts with [M(mu-OH)(COD)]2 (M = Rh, Ir) to give the corresponding tetranuclear
      metallomacrocycle derivatives [Cp*Ti{(OOC)(2)py}(mu-O)M(COD)]2 [M = Rh (6); Ir
      (7)]. The molecular structure of 6 has been established by X-ray diffraction.

PMID- 16804581
TI  - A new family of oxide ion conductors based on tricalcium oxy-silicate.
AB  - Tricalcium oxy-silicates, Ca3(SiO4)O and Ca2.93Mg0.07(Si0.98Al0.02O4)O0.99
      [square]0.01, have been prepared as crystalline single phases. Ca3(SiO4)O and
      Ca2.93Mg0.07(Si0.98Al0.02O4)O0.99 [square]0.01 have triclinic and monoclinic
      structures, respectively. The samples show oxide anion conductivity with a small
      p-type electronic contribution under oxidizing conditions. At 1023 K, the oxide
      transport numbers range between 0.97 and 0.85 from reducing (dry 5%-H2-Ar/air
      gradient) to oxidizing (O2/air gradient) conditions in the 1023-1173 K interval.
      The thermal analyses showed a large weight loss on heating due to the presence of
      water in the materials. The monoclinic compound has ionic conductivities higher
      than those of the triclinic stoichiometric oxy-silicate, as expected due to the
      introduction of oxide vacancies. Typical total conductivities for these un
      optimised solids are 10(-5)-10(-4) S cm(-1) at 1100 K. These compounds may
      contain a small amount of water, approximately 0.05 H2O moles per chemical
      formula, and they display an important proton contribution under a humidified
      atmosphere.

PMID- 16804582
TI  - Mechanistic study on the coupling reaction of aryl bromides with arylboronic
      acids catalyzed by (iminophosphine)palladium(0) complexes. Detection of a
      palladium(II) intermediate with a coordinated boron anion.
AB  - The complexes [Pd(eta2-dmfu)(P-N)] [P-N = 2-(PPh2)C6H4-1-CH=NR, R = C(6)H(4)OMe
      4; CHMe2; C6H3Me2-2,6; C6H3(CHMe2)-2,6] react with an excess of BrC6H4R1-4 (R1=
      CF3; Me) yielding the oxidative addition products [PdBr(C6H4R1-4)(P-N)] at
      different rates depending on R [C6H4OMe-4 > C6H3(CHMe2)-2,6 > CHMe2 approximately
      C6H3Me2-2,6] and R1 (CF3>> Me). In the presence of K2CO3 and activated olefins
      (ol = dmfu, fn), the latter compounds react with an excess of 4-R2C6H4B(OH)2 (R2=
      H, Me, OMe, Cl) to give [Pd(eta2-ol)(P-N)] and the corresponding biaryl through
      transmetallation and fast reductive elimination. The transmetallation proceeds
      via a palladium(II) intermediate with an O-bonded boron anion, the formation of
      which is markedly retarded by increasing the bulkiness of R. The intermediate was
      isolated for R = CHMe2, R1 = CF3 and R2= H. The boron anion is formulated as a
      diphenylborinate anion associated with phenylboronic acid and/or as a
      phenylboronate anion associated with diphenylborinic acid. In general, the
      oxidative addition proceeds at a lower rate than transmetallation and represents
      the rate-determining-step in the coupling reaction of aryl bromides with
      arylboronic acids catalyzed by [Pd(eta2-dmfu)(P-N)].

PMID- 16804583
TI  - Bonding modes of stanna-closo-dodecaborate: eta1(Sn) to eta3(BH) rearrangement
      reactions in zwitterionic stanna-closo-dodecaborate ruthenium complexes.
AB  - Reaction of the stanna-closo-dodecaborate salt [Bu3MeN]2[SnB11H11] with the
      dimeric ruthenium complex [Ru2(mu-Cl)3(triphos)2]Cl (triphos = {MeC(CH2PPh2)3})
      in refluxing acetonitrile yields the zwitterionic compound
      [Ru(SnB11H11)(MeCN)2(triphos)] (4) which has been characterized by single-crystal
      X-ray diffraction analysis and solid-state NMR spectroscopy. Refluxing the
      zwitterion in acetone leads to an eta1(Sn) to eta3(BH) rearrangement with
      formation of [Ru(SnB1)H11)(triphos)] (5) whose structure has been confirmed by X
      ray diffraction and multinuclear NMR spectroscopy in solution and in the solid
      state. Furthermore, two isomeric zwitterions fac- and mer
      [Ru(SnB11H11)(dppb)(MeCN)3] (6a, 6b) and their rearrangement reactions as well as
      their NMR properties are described.

PMID- 16804584
TI  - Group 12 metal monoselenocarboxylates: synthesis, characterization, structure and
      their transformation to metal selenide (MSe; M = Zn, Cd, Hg) nanoparticles.
AB  - Reactions of [MCl2(tmeda)] with potassium salts of monoselenocarboxylic acids
      gave complexes of the general formula [M(SeCOR)2(tmeda)] (M = Zn, Cd; R = Ph,
      Tol; Tol = C6H4-p-CH3; tmeda = Me2NCH2CH2NMe2). The analogous mercury complexes
      were unstable at room temperature and afforded HgSe nanoparticles during the
      course of reaction. All the complexes were characterized by elemental analysis,
      IR, UV-vis, NMR (1H, 13C, 77Se, 113Cd) data. The X-ray structural analysis of
      [Cd(SeCOPh)2(tmeda)] revealed that the complex is a discrete monomer having an
      approximate tetrahedral coordination environment around the central metal atom
      with monodentate (Se-bonded) selenocarboxylates. Thermal behavior of these
      complexes was studied by TG analysis. Pyrolysis in a furnace or in HDA
      (hexadecylamine) gave MSe nanoparticles, which were characterized by XRD, EDAX,
      SEM and absorption spectroscopy.

PMID- 16804585
TI  - More than technology alone.

PMID- 16804586
TI  - Dissolvable membranes as sensing elements for microfluidics based
      biological/chemical sensors.
AB  - We demonstrate a chemical and biological sensing mechanism in microfluidics that
      transduces chemical and biological signals to electrical signals with large
      intrinsic amplification without need for complex electronics. The sensing
      mechanism involves a dissolvable membrane separating a liquid sample chamber from
      an interdigitated electrode. Dissolution of the membrane (here, a disulfide cross
      linked poly(acrylamide) hydrogel) in the presence of a specific target (here, a
      reducing agent-dithiothreitol) allows the target solution to flow into contact
      with the electrode. The liquid movement displaces the air dielectric with a
      liquid, leading to a change (open circuit to approximately 1 kOmega) in the
      resistance between the electrodes. Thus, a biochemical event is transduced into
      an electrical signal via fluid movement. The concentration of the target is
      estimated by monitoring the difference in dissolution times of two juxtaposed
      sensing membranes having different dissolution characteristics. No dc power is
      consumed by the sensor until detection of the target. A range of targets could be
      sensed by defining membranes specific to the target. This sensing mechanism might
      find applications in sensing targets such as toxins, which exhibit enzymatic
      activity.

PMID- 16804587
TI  - Switchable surface traps for injectable bead-based chromatography in PDMS
      microfluidic channels.
AB  - We report here a reversible microchannel surface capture system for stimuli
      responsive grafted bioanalytical beads. Poly(N-isopropylacrylamide) (PNIPAAm) was
      grafted onto polydimethylsiloxane (PDMS) surfaces by a UV-mediated graft
      polymerization from a photoinitiator that was preadsorbed in the channel wall.
      The surface grafting density and resulting switchable hydrophilic/hydrophobic
      properties were controlled by varying the photo-illumination times and/or the
      initiator concentration. At limiting PNIPAAm-graft densities, the surfaces
      demonstrated minimal contact angles of 35 degrees below the lower critical
      solution temperature (LCST) and maximal contact angles of 82 degrees above it.
      These contact angles could be varied depending on the graft density. The surface
      grafts are spatially limited to the photo-illuminated region to define where the
      trap is constructed. The surface traps capture PNIPAAm-grafted nanobeads
      uniformly above the LCST and facilitate their rapid release as the temperature is
      reversed to below the LCST. This dual surface trap and injectable chromatography
      system could be useful in many applications, such as affinity separations,
      immunoassays, and enzyme bioprocesses, by providing for the controlled capture
      and release of chromatography beads.

PMID- 16804590
TI  - ATR-FTIR spectroscopic imaging with expanded field of view to study formulations
      and dissolution.
AB  - Fourier transformed infrared (FTIR) spectroscopic imaging in combination with a
      novel attenuated total reflection (ATR) accessory with an expanded field of view
      has been applied to simultaneously obtain infrared spectra of more than 150
      miniature samples, and to study the dissolution process of several different
      formulations in separate mini-channels simultaneously. This is the first time
      FTIR spectroscopic imaging using such an ATR accessory with an expanded field of
      view has been reported. The resultant imaging area with this approach was found
      to be ca. 15.4 x 21.4 mm(2) (6 x expansion). The potential of this approach
      includes imaging up to 440 samples simultaneously. The same accessory was used to
      prepare mini-channels (4 mm wide, 15 mm long and 0.5 mm deep) which were made of
      a PDMS grid that was self-adhered to the surface of the ATR crystal. Different
      molecular weights of poly(ethylene glycol) (PEG), with or without the addition of
      ibuprofen, have been used as model pharmaceutical formulations and chemical
      imaging of the simultaneous dissolution of five different formulations of
      PEG/ibuprofen has been demonstrated. Direct comparison between these different
      formulations under identical conditions was possible due to this imaging
      approach.

PMID- 16804588
TI  - Measurement of cell migration in response to an evolving radial chemokine
      gradient triggered by a microvalve.
AB  - We describe a novel chemotaxis assay based on the microvalve-actuated release of
      a chemoattractant from a cell-free microchamber into a cell-containing
      microchamber. The microvalve chemotaxis device (microVCD) was placed on the stage
      of a conventional inverted microscope to obtain time-lapse micrographs of
      neutrophils migrating in a radially-symmetric evolving gradient of the
      chemotactic factor CXCL8/Interleukin-8. A fluorescent tracer was added to the
      CXCL8 solution to visualize the evolution of the gradient profile, so that at
      each time point the cell positions could be assigned CXCL8 concentration values.
      Tracking of individual neutrophils for 90 minutes showed that (a) the neutrophil
      migratory response is, on average, radially directed towards the CXCL8 source;
      (b) significant non-radial displacements occur frequently; and (c) there is
      considerable heterogeneity in the migration speeds and directions amongst the
      neutrophil population. A custom-made imaging analysis tool was used to extract
      measurements of migratory behavior such as speed, velocity along the gradient's
      radial axis, and the cosine of the turning angle as a function of CXCL8
      concentration. The microVCD can be easily adapted to study the migratory behavior
      of cultured cells other than neutrophils.

PMID- 16804589
TI  - Simple and versatile methods for the fabrication of arrays of live mammalian
      cells.
AB  - Single-step methods for the generation of patterned surfaces on hydrogels are
      presented. Poly(vinyl alcohol) films covalently bonded on glass cover slips and
      commercially available hydrogel-coated polystyrene plates were used as cell
      repellent surfaces. Cell-adhesive domains were created by spotting dilute
      solutions of sodium hypochlorite onto the surfaces. Alternatively, domains
      supporting cell attachment were created by exposure to UV light from a xenon
      excimer lamp, employing a contact mask. Rat skeletal myoblast cells, HEK 293
      human embryonic kidney cells and Caco-2 colon carcinoma cells adhered and spread
      exclusively on modified areas. The surfaces are durable for weeks under cell
      culture conditions and re-usable after removal of the cells by trypsin treatment.
      Arrays of adhesive spots seeded with cells at a low density permitted dynamic
      monitoring of cell proliferation. Selected colonies can be harvested from the
      surfaces by means of local trypsination. Thus, these techniques may provide
      useful tools for the isolation of clonal cell populations. Additionally, we
      demonstrate the possibility of surface-mediated gene delivery from the micro
      patterns. We show that DNA, complexed with a lipid reagent, can be adsorbed on
      modified poly(vinyl alcohol) coatings, resulting in spatially controlled adhesion
      and reverse transfection of HEK 293 cells.

PMID- 16804591
TI  - A microfluidic device for continuous, real time blood plasma separation.
AB  - A microfluidic device for continuous, real time blood plasma separation is
      introduced. The principle of the blood plasma separation from blood cells is
      supported by the Zweifach-Fung effect and was experimentally demonstrated using
      simple microchannels. The blood plasma separation device is composed of a blood
      inlet, a bifurcating region which leads to a purified plasma outlet, and a
      concentrated blood cell outlet. It was designed to separate blood plasma from an
      initial blood sample of up to 45% inlet hematocrit (volume percentage of cells).
      The microfluidic network was designed using an analogous electrical circuit, as
      well as analytical and numerical studies. The functionality of this device was
      demonstrated using defibrinated sheep blood. During 30 minutes of continuous
      blood infusion through the device, all the erythrocytes (red blood cells)
      traveled through the device toward the concentrated blood outlet while only the
      plasma was separated at the bifurcating regions and flowed towards the plasma
      outlet. The device has been operated continuously without any clogging or
      hemolysis of cells. The experimentally determined plasma selectivity with respect
      to blood hematocrit level was almost 100% regardless of the inlet hematocrit. The
      total plasma separation volume percent varied from 15% to 25% with increasing
      inlet hematocrit. Due to the device's simple structure and control mechanism,
      this microdevice is expected to be used for highly efficient continuous, real
      time cell-free blood plasma separation from blood samples for use in lab on a
      chip applications.

PMID- 16804592
TI  - Simulating molecular shuttle movements: towards computer-aided design of
      nanoscale transport systems.
AB  - Molecular shuttles based on the motor protein kinesin and microtubule filaments
      have the potential to extend the lab-on-a-chip paradigm to nanofluidics by
      enabling the active, directed and selective transport of molecules and
      nanoparticles. Based on experimentally determined parameters, in particular the
      trajectory persistence length of a microtubule gliding on surface-adhered kinesin
      motors, we developed a Monte-Carlo simulation, which models the transport
      properties of guiding structures, such as channels, rectifiers and concentrators,
      and reproduces the properties of several experimentally realized systems. Our
      tool facilitates the rational design of individual guiding structures as well as
      whole networks, and can be adapted to the simulation of other nanoscale transport
      systems.

PMID- 16804593
TI  - Microchip-based one step DNA extraction and real-time PCR in one chamber for
      rapid pathogen identification.
AB  - Optimal detection of a pathogen present in biological samples depends on the
      ability to extract DNA molecules rapidly and efficiently. In this paper, we
      report a novel method for efficient DNA extraction and subsequent real-time
      detection in a single microchip by combining laser irradiation and magnetic
      beads. By using a 808 nm laser and carboxyl-terminated magnetic beads, we
      demonstrate that a single pulse of 40 seconds lysed pathogens including E. coli
      and Gram-positive bacterial cells as well as the hepatitis B virus mixed with
      human serum. We further demonstrate that the real-time pathogen detection was
      performed with pre-mixed PCR reagents in a real-time PCR machine using the same
      microchip, after laser irradiation in a hand-held device equipped with a small
      laser diode. These results suggest that the new sample preparation method is well
      suited to be integrated into lab-on-a-chip application of the pathogen detection
      system.

PMID- 16804594
TI  - A multifunctional micro-fluidic system for dielectrophoretic concentration
      coupled with immuno-capture of low numbers of Listeria monocytogenes.
AB  - In this study, we demonstrated a micro-fluidic system with multiple functions,
      including concentration of bacteria using dielectrophoresis (DEP) and selective
      capture using antibody recognition, resulting in a high capture efficiency of
      bacterial cells. The device consisted of an array of oxide covered interdigitated
      electrodes on a flat silicon substrate and a approximately 16 microm high and
      approximately 260 microm wide micro-channel within a PDMS cover. For selective
      capture of Listeria monocytogenes from the samples, the channel surface was
      functionalized with a biotinylated BSA-streptavidin-biotinylated monoclonal
      antibody sandwich structure. Positive DEP (at 20 V(pp) and 1 MHz) was used to
      concentrate bacterial cells from the fluid flow. DEP could collect approximately
      90% of the cells in a continuous flow at a flow rate of 0.2 microl min(-1) into
      the micro-channel with concentration factors between 10(2)-10(3), in sample
      volumes of 5-20 microl. A high flow rate of 0.6 microl min(-1) reduced the DEP
      capture efficiency to approximately 65%. Positive DEP attracts cells to the edges
      of the electrodes where the field gradient is the highest. Cells concentrated by
      DEP were captured by the antibodies immobilized on the channel surface with
      efficiencies of 18 to 27% with bacterial cell numbers ranging from 10(1) to 10(3)
      cells. It was found that DEP operation in our experiments did not cause any
      irreversible damage to bacterial cells in terms of cell viability. In addition,
      increased antigen expression (antigens to C11E9 monoclonal antibody) on cell
      membranes was observed following the exposure to DEP.

PMID- 16804595
TI  - Microchemostat-microbial continuous culture in a polymer-based, instrumented
      microbioreactor.
AB  - In a chemostat, microbial cells reach a steady state condition at which cell
      biomass production, substrates and the product concentrations remain constant.
      These features make continuous culture a unique and powerful tool for biological
      and physiological research. We present a polymer-based microbioreactor system
      integrated with optical density (OD), pH, and dissolved oxygen (DO) real-time
      measurements for continuous cultivation of microbial cells. Escherichia coli (E.
      coli) cells are continuously cultured in a 150 microL, membrane-aerated, well
      mixed microbioreactor fed by a pressure-driven flow of fresh medium through a
      microchannel. Chemotaxisial back growth of bacterial cells into the medium feed
      channel is prevented by local heating. Using poly(ethylene glycol) (PEG)-grafted
      poly(acrylic acid) (PAA) copolymer films, the inner surfaces of poly(methyl
      methacrylate) (PMMA) and poly(dimethylsiloxane) (PDMS) of the microbioreactor are
      modified to generate bio-inert surfaces resistant to non-specific protein
      adsorption and cell adhesion. The modified surfaces of microbioreactor
      effectively reduce wall growth of E. coli for a prolonged period of cultivation.
      Steady state conditions at different dilution rates are demonstrated and
      characterized by steady OD, pH, and DO levels.

PMID- 16804596
TI  - Direct measurement of the impact of impaired erythrocyte deformability on
      microvascular network perfusion in a microfluidic device.
AB  - The ability of red blood cells (RBCs, erythrocytes) to deform and pass through
      capillaries is essential for continual flow of blood in the microvasculature,
      which ensures an adequate supply of oxygen and nutrients, prompt removal of
      metabolic waste products, transport of drugs and hormones, and traffic of
      circulating cells to and from all living tissues. This paper presents a novel
      tool for evaluating the impact of impaired deformability of RBCs on the flow of
      blood in the microvasculature by directly measuring perfusion of a test
      microchannel network with dimensions and topology similar to the real
      microcirculation. The measurement of microchannel network perfusion is compared
      with RBC filtration -- a conventional assay of RBC deformability. In contrast to
      RBC filterability, network perfusion depends linearly on RBC deformability
      modulated by graded exposure to glutaraldehyde, showing a higher sensitivity to
      small changes of deformability. The direct measurement of microchannel network
      perfusion represents a new concept for the field of blood rheology and should
      prove beneficial for basic science and clinical applications.

PMID- 16804597
TI  - Dose-dependent cell-based assays in V-shaped microfluidic channels.
AB  - The capability of lab-on-a-chip technologies in controlling cell transportation,
      generating concentration gradients, and monitoring cellular responses offers an
      opportunity to integrate dose-dependent cell-based bioassays on a chip. In this
      study, we have developed microfluidic modules featured with channel components
      and sandbag structures for positioning biological cells within the microchip. We
      have demonstrated that by geometric modulation of the microchannel architectures,
      it is possible to immobilize individual cells at desired locations with
      controllable numbers, to generate defined concentration gradients at various
      channel lengths, and to improve the efficiency and reproducibility in data
      acquisition. The microfluidic module was used to exercise a series of cell-based
      assays, including the measurement of kinetics and dynamics of intracellular
      enzymatic activities, the analysis of cellular response under the stimulation of
      two chemicals with defined concentration profiles, and the study of laser
      irradiation effect on cellular uptake of photosensitizers. The results
      demonstrated the capabilities of the microfluidic module for simultaneously
      conducting multiple sets of dose-dependent, cell-based bioassays, and for
      quantitatively comparing responses of individual cells under various
      stimulations.

PMID- 16804598
TI  - Experimental characterization of hydrodynamic dispersion in shallow
      microchannels.
AB  - Hydrodynamic dispersion in shallow microchannels with almost parabolic cross
      sectional shapes and with heights much less than their widths is studied
      experimentally. Both long serpentine channels and rotary mixers are used. The
      experimental results demonstrate that the dispersion depends on the width rather
      than the height of the channel. The results are in quantitative agreement with a
      recently proposed theory of dispersion in shallow channels.

PMID- 16804599
TI  - High fidelity, high yield production of microfluidic devices by hot embossing
      lithography: rheology and stiction.
AB  - We discuss thermoforming of thermoplastic polymers for the hot-embossing
      lithographic (HEL) fabrication of microfluidic chips near equilibrium conditions
      that minimize elastic recoil for optimal motif replication. While HEL is often
      simplistically described as the transfer of micro- and nano-motifs into heat
      softened thermoplastic materials, we describe our rational approach to selecting
      appropriate processing parameters.

PMID- 16804600
TI  - Grafting epoxy-modified hydrophilic polymers onto poly(dimethylsiloxane)
      microfluidic chip to resist nonspecific protein adsorption.
AB  - In order to achieve a simple covalent hydrophilic polymer coating on
      poly(dimethylsiloxane) (PDMS) microfluidic chip, epoxy modified hydrophilic
      polymers were synthesized in aqueous solution with a persulfate radical
      initiation system, and crosslinked onto PDMS pretreated by oxygen plasma and
      silanized with 3-aminopropyl-triethoxysilanes (APTES). Glycidyl methacrylate
      (GMA) was copolymerized with acrylamide (poly(AAM-co-GMA)) or dimethylacrylamide
      (poly(DAM-co-GMA)), and graft polymerized with polyvinylpyrrolidone (PVP-g-GMA)
      or polyvinylalcohol (PVA-g-GMA). The epoxy groups in the polymers were determined
      by UV spectra after derivation with benzylamine. Reflection absorption infrared
      spectroscopy (RAIRS) confirmed covalent grafting of GMA-modified polymers onto
      PDMS surface. Electroosmotic flow (EOF) in the polymer grafted microchannel was
      strongly suppressed within the range pH 3-11. Surface adsorption of lysozyme and
      bovine serum albumin (BSA) was reduced to less than 10% relative to that on the
      native PDMS surface. On the GMA-modified polymer coated PDMS microchip, basic
      proteins, peptides, and sodium dodecyl sulfate (SDS) denatured proteins were
      separated successfully.

PMID- 16804602
TI  - Manipulating the generation of Ca-alginate microspheres using microfluidic
      channels as a carrier of gold nanoparticles.
AB  - In this paper the manipulation of Ca-alginate microspheres, using a microfluidic
      chip, for the encapsulation of gold nanoparticles is presented. Our strategy is
      based on hydrodynamic-focusing on the forming of a series of self-assembling
      sphere structures, the so-called water-in-oil (w/o) emulsions, in the cross
      junction microchannel. These fine emulsions, consisting of aqueous Na-alginates,
      are then dripped into a solution of 20% calcium salt to accomplish Ca-alginate
      microspheres in an efficient manner. Experimental data show that microspheres
      with diameters ranging from 50 microm to 2000 microm with a variation less than
      5% were precisely generated. The size and gap of the droplets are tunable by
      adjusting the relative sheath/sample flow rate ratio. Furthermore, we applied
      them to encapsulated gold nanoparticles, and this one shot operation performs the
      'Lab on a Chip'.

PMID- 16804601
TI  - Capillary liquid chromatography-microchip atmospheric pressure chemical
      ionization-mass spectrometry.
AB  - A miniaturized nebulizer chip for capillary liquid chromatography-atmospheric
      pressure chemical ionization-mass spectrometry (capillary LC-microchip APCI-MS)
      is presented. The APCI chip consists of two wafers, a silicon wafer and a Pyrex
      glass wafer. The silicon wafer has a DRIE etched through-wafer nebulizer gas
      inlet, an edge capillary insertion channel, a stopper, a vaporizer channel and a
      nozzle. The platinum heater electrode and pads for electrical connection were
      patterned on to the Pyrex glass wafer. The two wafers were joined by anodic
      bonding, creating a microchip version of an APCI-source. The sample inlet
      capillary from an LC column is directly connected to the vaporizer channel of the
      APCI chip. The etched nozzle in the microchip forms a narrow sample plume, which
      is ionized by an external corona needle, and the formed ions are analyzed by a
      mass spectrometer. The nebulizer chip enables for the first time the use of low
      flow rate separation techniques with APCI-MS. The performance of capillary LC
      microchip APCI-MS was tested with selected neurosteroids. The capillary LC
      microchip APCI-MS provides quantitative repeatability and good linearity. The
      limits of detection (LOD) with a signal-to-noise ratio (S/N) of 3 in MS/MS mode
      for the selected neurosteroids were 20-1000 fmol (10-500 nmol l(-1)). LODs (S/N =
      3) with commercial macro APCI with the same compounds using the same MS were
      about 10 times higher. Fast heat transfer allows the use of the optimized
      temperature for each compound during an LC run. The microchip APCI-source
      provides a convenient and easy method to combine capillary LC to any API-MS
      equipped with an APCI source. The advantages and potentials of the microchip APCI
      also make it a very attractive interface in microfluidic APCI-MS.

PMID- 16804603
TI  - Brilliant opportunities across the spectrum.
AB  - Third generation synchrotron light sources provide stable, tuneable light of
      energy up to the hard X-ray region. The gain of a trillion in brightness as
      compared to a conventional laboratory X-ray source transforms the opportunities
      for establishing structure-function relationships. The light may be quasi
      continuous or pulsed, have controllable polarisation and have coherence lengths
      larger than the sample size. The high brightness provides a basis for adding time
      and spatial resolution to X-ray scattering and spectroscopy. It may also be used
      to identify very specific information about the magnetic properties of atoms
      within materials, element specific vibrations, and local structural descriptions
      identified with chemical speciation. More demanding scattering and diffraction
      problems can be solved such as weakly scattering materials, large unit cells and
      structural entities. The high collimation of the source also provides enhanced
      spectroscopic and diffraction resolution that gives more insight into molecular,
      extended and supramolecular structures. The length scales can be bridged from the
      atomic up to that of visible light microscopy and buried features within
      materials can be observed with the appropriate energy. With an increased emphasis
      on ease of use, such capabilities are open to exploitation for chemical
      challenges.

PMID- 16804604
TI  - Theoretical study of the ground and excited states of 7-methyl guanine and 9
      methyl guanine: comparison with experiment.
AB  - The keto-enol tautomerization of 7-methyl-guanine and 9-methyl-guanine in the
      excited state was investigated using the time-dependent DFT (TDDFT) method. For
      both species, the potential energy surfaces of the ground state and two lowest
      singlet excited states (due to pi-->pi* and n-->pi* transitions) have been
      investigated and their features discussed in terms of consequences on the excited
      state dynamics. The findings suggest that, for both species, the state due to the
      n-->pi* transition, suspected to be an intermediate in the excited state
      deactivation, exhibits two minima with the second minimum characterized by an
      elongated N1-H distance. This structure, intermediate between enol and keto
      tautomers, might play a role in the excited state relaxation. The existence of
      this second well, however, is observed in both 7- and 9-methyl-guanine, which
      suggests that it cannot account alone for the different photophysical behavior of
      these species.

PMID- 16804605
TI  - A molecular dynamics study of human endostatin and its synthetic fragments with
      antiangiogenic properties.
AB  - Human endostatin is one of the better characterized endogenous angiogenesis
      inhibitors, and its ability to modulate vascularization of tumours could be of
      great therapeutic interest. These properties are not exclusive to the full-length
      protein, but are shared by some of its synthetic fragments. A number of research
      groups have partitioned human endostatin in different peptides and have
      investigated their activity, in order to collect a body of experimental data
      which could be important in shedding new light on their structure-activity
      relationships. It was also reported that a small active fragment can become
      inactive when contained in a larger fragment, revealing an apparent discrepancy
      in the experimental results. Very few studies have been devoted to the
      computational analysis of these systems and to the rationalization of their
      properties using molecular modelling. Through molecular dynamics simulations of
      human endostatin and of four synthetic fragments, we have been able to
      rationalize the experimental findings. In particular, we have identified a
      pattern consisting of six amino acids, namely R-R(G)-A-D-R-A, which appears to be
      an active epitope if it is properly exposed to the solvent. Interestingly, this
      pattern can be already present in sequential order in the primary structure, or
      it can be generated by the spatial approach of two groups of residues, far apart
      in the primary structure, as an effect of the peptide folding. Comparing the
      structural features and the time evolution of all the simulated peptides we
      provide a coherent explanation of their activity or inactivity.

PMID- 16804606
TI  - A simple algebraic derivation of the Obara-Saika scheme for general two-electron
      interaction potentials.
AB  - A new derivation is presented for the recursion relation of Obara and Saika (OS)
      for two-electron integrals over Gaussian basis functions for general interaction
      potentials g(r(12)), where r(12) denotes the interelectronic distance. The
      decisive vertical OS recursion is proved directly from the recursion relation for
      Gaussian basis functions and the structure of the primitive integral expression
      for s functions. The resulting simple formulae greatly facilitate extensions of
      OS-based codes for Coulomb interactions to general g, which has already proved
      useful in implementations. The present derivation further extends the validity of
      the OS recursion beyond interactions covered so far.

PMID- 16804607
TI  - Infrared spectroscopy of the Li+(H2O)Ar complex: the role of internal energy and
      its dependence on ion preparation.
AB  - The internal energy or effective temperature of cluster ions has become an
      important issue in characterizing the structures observed in these species. This
      report considers the role played by the method of ion preparation (laser
      vaporization-supersonic expansion versus ion impact-evaporative cooling) in
      governing the internal energy of a specific species, Li(+)(H(2)O)Ar. Vibrational
      predissociation spectroscopy of the O-H stretch modes revealed rotational
      features, which were used to characterize the structure and effective rotational
      temperature of the cluster ion. In addition, the impact of the lithium ion on the
      H(2)O molecule was analyzed in terms of the vibrational frequency shifts,
      relative IR intensities, and H(2)O geometry.

PMID- 16804609
TI  - Raman spectroscopic study of hydrogen ordered ice XIII and of its reversible
      phase transition to disordered ice V.
AB  - Raman spectra of recovered ordered H(2)O (D(2)O) ice XIII doped with 0.01 M HCl
      (DCl) recorded in vacuo at 80 K are reported in the range 3600-200 cm(-1). The
      bands are assigned to the various types of modes on the basis of isotope ratios.
      On thermal cycling between 80 and 120 K, the reversible phase transition to
      disordered ice V is observed. The remarkable effect of HCl (DCl) on orientational
      ordering in ice V and its phase transition to ordered ice XIII, first reported in
      a powder neutron diffraction study of DCl doped D(2)O ice V (C. G. Salzmann, P.
      G. Radaelli, A. Hallbrucker, E. Mayer, J. L. Finney, Science, 2006, 311, 1758),
      is demonstrated by Raman spectroscopy and discussed. The dopants KOH and HF have
      only a minor effect on hydrogen ordering in ice V, as shown by the Raman spectra.

PMID- 16804608
TI  - On the connection between optical absorption/extinction and SERS enhancements.
AB  - Several aspects of the connection between the absorption/extinction spectra and
      the enhancement in surface enhanced Raman scattering (SERS) are analyzed and
      discussed. It is shown that in many standard situations the spatial distribution
      of the resonance plays a role for the difference between extinction/absorption
      and SERS enhancement and that the connection between both can be very indirect
      and, in many cases, misleading. This clarifies several misconceptions often found
      in the literature.

PMID- 16804610
TI  - Muon spin relaxation study of Zr(H2PO4)(PO4).2H2O.
AB  - Muon spin relaxation has been used to study the muon dynamics in the layered
      zirconium phosphate Zr(H(2)PO(4))(PO(4)).2H(2)O as a function of temperature.
      Radiofrequency decoupling was used to establish the origin of the local dipolar
      field as coupling with (1)H spins. Muons were trapped at two sites, one
      identified as HMuO and the other consistent with PO-Mu on the basis of their zero
      field second moments. Although a small decrease in the local nuclear dipolar
      field was seen with temperature, the muons remained essentially static over the
      temperature range 20-300 K.

PMID- 16804611
TI  - Do zeolite precursor species really exist in aqueous synthesis media?
AB  - The authors of a recent report in this journal (Houssin, et al., Phys. Chem.
      Chem. Phys., 2003, 5, 3518, ) claim that a tetrapropylammonium (TPA) silicate
      mixture with molar composition 4.41 TPAOH : 10 SiO(2) : 117 H(2)O contains high
      concentrations of two silicate oligomers, the prismatic double five-ring and a
      novel pentacyclic dodecamer. The latter species is derivative of the framework
      structure of silicalite-1, a MFI-type zeolite that spontaneously crystallizes
      from this system, and, indeed, the authors declare it to be a "nanoprecursor" in
      the TPA-mediated growth of silicalite-1. Using two-dimensional (29)Si COSY NMR
      spectroscopy to examine an equivalent mixture enriched in the (29)Si isotope, we
      show that the published peak assignments are erroneous. The signal assigned to
      the double five-ring corresponds, in reality, to the well-characterized
      pentacyclic octamer, while the three signals assigned to the pentacyclic
      dodecamer arise from three completely separate species. We find no evidence,
      therefore, to support the suggestion that silicalite-1 is formed by sequential
      condensation of precursor species any more complex than the simple orthosilicate
      anion.

PMID- 16804612
TI  - Kinetic study of the reactions of the sodium dimer (Na2) with a range of
      atmospheric species.
AB  - The reactions of Na(2) with a series of atmospheric constituents were studied
      using a fast flow tube with detection of Na(2) by laser induced fluorescence at
      656.2 nm [Na(2)(A(1)Sigma(+)(u) - X(1)Sigma(+)(g))]. The resulting rate
      coefficients at 298 K for the reactions of Na(2) with OH, O(2), NO(2), NO, O(3),
      H, H(2) and H(2)O are: (1.01(+0.35)(-0.25)) x 10(-10), (2.95 +/- 0.46) x 10(-11),
      (1.79(+0.51)(-0.31)) x 10(-10), (1.33 +/- 0.16) x 10(-11), (8.0(+24)(-3.0)) x 10(
      11), < or =6 x 10(-12), <or =4 x 10(-15), and <or =3 x 10(-13) cm(3) molecule(-1)
      s(-1), respectively. The quoted uncertainties include measurement imprecision at
      the 1sigma level, and systematic errors. The reaction between Na(2) and OH
      produces chemiluminescence at 589 nm [Na(3(2)P(J) - 3(2)S(1/2))], with a measured
      branching ratio of (7.6(+15.0)(-3.7)) x 10(-3). The reaction enthalpies are
      calculated using quantum theory at the Complete Basis Set (CBS-Q) level; all
      reactions except Na(2) + H(2)O and Na(2) + H(2) are exothermic. The surprisingly
      slow reaction of Na(2) with OH is explained using trajectory calculations and
      consideration of the splitting between the covalent and ionic surfaces involved
      in the reaction, coupled with the Landau-Zener formalism. The small upper limit
      to the rate coefficient for the strongly exothermic reaction Na(2) + H appears to
      be a striking example of the light atom anomaly where the reaction is
      kinematically constrained.

PMID- 16804613
TI  - A density functional theory based study of the microscopic structure and dynamics
      of aqueous HCl solutions.
AB  - The aqueous solvation of hydrochloric acid is studied using density functional
      theory based molecular dynamics simulations at two concentrations. The large
      simulation boxes that we use allow us to investigate larger-scale structures such
      as the water-bridged chloride ion network. We find a strong concentration
      dependence for almost all structural and dynamical properties. Excess protons are
      mostly present both as Eigen and Zundel structures, either as a direct hydronium
      chloride contact-ion pair or a solvent-separated ion pair. Increasing the
      concentration has a detrimental effect on the natural hydrogen bonded network of
      water molecules. This effect is visible in our studies as a decrease in the
      persistence time of the solvation shells around the chloride ions. Also the
      number of proton hops, determined by a new and well defined identification
      procedure, suffers from the breakdown of the natural hydrogen bond network.

PMID- 16804614
TI  - Infrared-induced reaction of Cl atoms trapped in solid parahydrogen.
AB  - The 355 nm photodissociation of Cl(2) trapped in a solid parahydrogen matrix at 2
      K leads to the formation of isolated Cl photofragments. At these low temperatures
      (k(B)T approximately 1.4 cm(-1)), the Cl atoms can not react with the
      parahydrogen matrix since the reaction Cl + H(2)(v = 0, j = 0) --> HCl(v = 0, j =
      0) + H is endothermic by 360 cm(-1). Irradiation of the Cl atom doped
      parahydrogen solid with broadband infrared radiation from 4000 cm(-1) to 5000 cm(
      1) induces reaction of atomic Cl with the parahydrogen matrix to form HCl. The
      infrared-induced chemistry is attributed to solid parahydrogen absorptions that
      lead to the creation of vibrationally excited H(2)(v = 1), which supply the
      necessary energy to induce reaction. The kinetics of this low temperature
      infrared-induced reaction is studied using Fourier Transform infrared
      spectroscopy of the HCl reaction product. The HCl formation kinetics is first
      order and the magnitude of the effective rate constant for the infrared-induced
      reaction depends on the properties of the near infrared radiation.

PMID- 16804615
TI  - Tryptophan-BODIPY: a versatile donor-acceptor pair for probing generic changes of
      intraprotein distances.
AB  - We demonstrate that Tryptophan (Trp) and N-(4,4-difluoro-5,7-dimethyl-4-bora
      3a,4a-diaza-s-indacene-3-yl)methyl iodoacetamide (BODIPY) is a suitable donor
      acceptor (D-A) pair for intraprotein distance measurements, applicable to the
      study of protein folding. The suitability of the Trp-BODIPY electronic energy
      transfer is exemplified on the extensively-characterised two-state protein, S6,
      from Thermus thermophilus. This protein has proved to be useful for the
      elucidation of folding cooperativity and nucleation, as well as the changes upon
      induction of structural transitions. For a comprehensive structural coverage,
      BODIPY molecules were anchored by Cys insertions at four different positions on
      the S6 surface. Trp residues at position 33 or 62 acted as donors of electronic
      energy to the BODIPY groups. None of the D-A pairs show any detectable difference
      in the folding kinetics (or protein stability), which supports the notion that
      the two-state transition of S6 is a highly concerted process. Similar results are
      obtained for mutants affecting the N- and C-terminus. The kinetic analyses
      indicate that changes of the transition state occur through local unfolding of
      the native state, rather than by a decrease of the folding cooperativity. The
      distances obtained from the analysis of the time-resolved fluorescence
      experiments in the native state were compared to those calculated from X-ray
      structure. As an additional measure, molecular dynamics simulations of the
      different protein constructs were performed to account for variability in the
      BODIPY location on the protein surface. The agreement between fluorescence and X
      ray data is quite convincing, and shows that energy transfer measurements between
      Trp and BODIPY can probe distances between ca. 17 to 34 A, with an error better
      than 10%.

PMID- 16804616
TI  - Counter-ion activity and microstructure in polyelectrolyte complexes as
      determined by osmotic pressure measurements.
AB  - We have investigated the activity of counter-ions at 60 degrees C through the
      osmotic coefficient K in solutions of anionic and cationic polyelectrolyte
      complexes of variable compositions. For excess of polyanion in the complexes
      (molar fraction of polycation f < 0.5), K increases as the polyanion is
      neutralized by the polycation (f getting closer to 0.5). By contrast, for an
      excess of polycation (f > 0.5), K stays constant or even slightly decreases as
      the polycation is getting neutralized by the polyanion. This asymmetric behavior
      depending on the charge of the complexes indicates that the globally negatively
      charged complexes are homogeneous and can be treated as a single polyelectrolyte
      of reduced linear charge density. On the other hand, the positively charged
      complexes show a micro-phase separation between neutral fully compensated
      microdomains and domains where the excess polycation is locally segregated. These
      two different microstructures are reminiscent of the coacervation and segregation
      regimes observed at higher concentrations and salinities, and also of
      polyelectrolyte complexes with oppositely charged surfactants. This
      interpretation is supported by two simple predictive models.

PMID- 16804617
TI  - Establishing the health risks of exposure to radiofrequency fields requires
      multidisciplinary research.

PMID- 16804618
TI  - Meta-analysis of mobile phone use and intracranial tumors.
AB  - OBJECTIVES: A summary of epidemiologic evidence regarding the effect of mobile
      phone use on intracranial tumor risk was obtained by means of a meta-analysis.
      METHODS: Reports of published studies on mobile phone use and intracranial tumors
      were sought. Altogether 12 relevant publications were identified from the PubMed
      database and reference lists of articles. Fixed or random effects analysis was
      carried out depending on the presence of heterogeneity between studies. Risk
      estimates were obtained for people who had used mobile phones for the longest
      periods of time (>5 years in most reports). A pooled estimate was calculated for
      all intracranial tumors combined and also separately for different histological
      tumor types. Separate analyses were conducted also based on the tumor location
      and type of mobile telephone network (NMT or GSM). RESULTS: Twelve studies with
      2780 cases gave a pooled odds ratio (OR) of 0.98 [95% confidence interval (95%
      CI) 0.83-1.16] for all intracranial tumors related to mobile phone use. For
      gliomas, the pooled OR was 0.96 (95% CI 0.78-1.18), for meningiomas it was 0.87
      (95% CI 0.72-1.05), and for acoustic neuromas it was 1.07 (95% CI 0.89-1.30).
      Little indication was found for increased risks of analogue or digital phone use
      or temporal or occipital tumors. CONCLUSIONS: The totality of evidence does not
      indicate a substantially increased risk of intracranial tumors from mobile phone
      use for a period of at least 5 years.

PMID- 16804619
TI  - Brain tumors and occupational exposures in a cohort of female textile workers in
      Shanghai, China.
AB  - OBJECTIVES: This study assessed the associations between brain tumors and
      specific processes and exposures among female textile workers in Shanghai, China.
      METHODS: A case-cohort study was conducted that was nested in a cohort of textile
      workers originally included in a randomized trial of breast self-examination.
      Incident brain tumor cases (N=114) were identified from 1989 to 1998 from a tumor
      and death registry operated by the Shanghai Textile Industry Bureau. A subcohort
      (N=3188), representing an age-stratified random sample of the entire cohort, was
      selected as a comparison group. Job-exposure matrices were created to assess
      historical exposures to specific agents, including quantitative assessments for
      cotton dust and endotoxin exposure. Cox proportional hazards modeling, modified
      according to a case-cohort design, was used to analyze associations between jobs
      and exposures and the risk of brain tumors. RESULTS: Employment in maintenance
      workshops was associated with an increased brain tumor incidence (ever-never
      exposed hazard ratio 2.36, 95% confidence interval 1.12-4.97), with increasing
      hazard ratios by duration of employment in maintenance jobs. Handling or
      processing wool fibers was associated with an increased risk of brain tumors, as
      was specific exposure to wool fibers; however, estimates did not increase with
      duration of employment. CONCLUSIONS: These results provide some preliminary
      suggestion that employment in textile industry maintenance jobs and exposure to
      wool products may be associated with an increased risk of brain tumors.

PMID- 16804620
TI  - Cancer incidence among farmers exposed to lindane while sheep dipping.
AB  - OBJECTIVES: The objective of this study was to determine whether site-specific
      cancer incidence among farmers exposed to the insecticide lindane (g
      hexachlorocyclohexane) while dipping sheep differs from that of the general
      population in Iceland. METHODS: Cohorts of 7882 men and 429 women, who, according
      to records on sheep dipping, were sheep owners, were followed from 1962 to 2003
      in the Cancer Registry for cancer incidence. The observed number of cancers was
      compared with expected values, calculated on the basis of person-years of risk
      and cancer incidence in the general population of Iceland. RESULTS: For men the
      standardized incidence ratio (SIR) for all cancer sites was 0.79, with a 95%
      confidence interval (95% CI) of 0.76-0.83. For both the men and the women a
      significantly increased risk for lip cancer was found, with SIR of 1.50 (95% CI
      1.08-2.04) and 9.09 (95% CI 1.02-32.82), respectively. The SIR for several cancer
      sites were lower than unity for both the men and women. Examples were cancers of
      the colon, rectum, pancreas, stomach, lungs, kidney, bladder, and brain and
      nervous system. CONCLUSIONS: The decreased risk of most cancers among these sheep
      farmers agrees with findings reported previously among farmers from other
      countries, as well as in Iceland. Cancer of the lip was the only cancer type in
      significant excess among both genders, and the stomach cancer rates were near
      unity, but, in previous studies on Icelandic farmers, an increase had been found
      for stomach cancer. The site-specific cancer incidence for sheep-dipping farmers
      did not differ substantially from that of the general population.

PMID- 16804621
TI  - Is an imbalance between physical capacity and exposure to work-related physical
      factors associated with low-back, neck or shoulder pain?
AB  - OBJECTIVES: This study investigates whether an imbalance between physical
      capacity and exposure to work-related physical factors is associated with low
      back, neck, or shoulder pain. METHODS: Data of the longitudinal study on
      musculoskeletal disorders, absenteeism, stress, and health (SMASH), with a follow
      up of 3 years (N=1789), were used. At baseline, physical capacity (isokinetic
      lifting strength, static muscle endurance, and mobility of the spine) and
      exposure to work-related physical factors were assessed. During the follow-up,
      low-back, neck, and shoulder pain were self-reported annually. "Imbalance" was
      defined as lower than median capacity combined with higher than median exposure,
      "high balance" was high capacity and high exposure, and "low balance" was low
      capacity and low exposure. RESULTS: For both the low-back and neck, imbalance
      between static endurance and working with flexed postures was a risk factor for
      pain [relative risk (RR) 1.35, 95% confidence interval (95% CI) 1.08-1.68, and RR
      1.36, 95% CI 0.96-1.91, respectively]. Low balance was also associated with low
      back pain (RR 1.29, 95% CI 1.04-1.68). Furthermore, low balance between
      isokinetic lifting strength and lifting exposure was a risk factor for low-back
      and neck pain [RR between 1.22 (95% CI 0.99-1.49) and 1.35 (95% CI 1.03-1.79)].
      No associations were found with shoulder pain. CONCLUSIONS: Some relationship
      between low-back and neck pain and combined measures of physical capacity with
      exposure to work-related physical factors seems to exist, but an imbalance
      between physical capacity and exposure was not found to yield higher risks than
      high balance or low balance.

PMID- 16804622
TI  - Relationship between hand-arm vibration exposure and onset time for symptoms in a
      heavy engineering production workshop.
AB  - OBJECTIVES: This study examined onset time for reported vascular and neurological
      symptoms in relation to the vibration load in a group of workers exposed to
      vibration. METHODS: Information on the self-stated year for the first occurrence
      of symptoms was collected by means of questionnaires. During interviews data were
      obtained on self-stated estimations of daily exposure time, type of tool, and
      number of months or years with different exposures. The estimations of the
      vibration magnitudes of exposure were based on conducted measurements. From these
      data, the individual vibration exposure at the time of onset of symptoms was
      calculated. RESULTS: The incidence was 25.6 and 32.9 per 1000 exposure years for
      vascular and neurological symptoms, respectively, in the group of workers. The
      first onset of symptoms appeared after an average of 12 years of exposure. For
      the workers, the symptoms of vascular or neurological disorders started after
      about the same number of exposure years. The calculated accumulated acceleration
      correlated best with the onset time of symptoms. CONCLUSIONS: It was concluded
      that, since the workers' exposure to vibration was below the action level
      established in the European vibration directive, the results suggest that the
      action level is not a safe level for avoiding vascular and neurological symptoms.

PMID- 16804623
TI  - Prevalent cardiovascular disease, risk factors and selection out of shift work.
AB  - OBJECTIVES: This study examines whether health-related selection out of shift
      work is likely to bias the association between shift work and cardiovascular
      disease (CVD). METHODS: Survey data on doctor-diagnosed CVD (myocardial
      infarction, angina, or hypertension) and risk factors (high blood pressure, high
      cholesterol concentration, obesity, and diabetes) were collected in 2000-2002 for
      a cohort of 7037 female nurses (5038 shift workers, 1999 day workers) in 21
      Finnish hospitals. The follow-up in 2004 determined those who had left their
      workplace or changed from shift work to day work. RESULTS: Among the shift
      workers, the age-adjusted odds for leaving the organization was 1.83 (95% CI 1.01
      3.32) times higher for those with prevalent diabetes and 2.21 (95% CI 1.12-4.39)
      times higher for those with three to four risk factors than for their
      counterparts with no diabetes or risk factors. The associations between CVD risk
      factors and leaving the organization were similar for the day workers. The
      prevalent CVD and risk factors did not predict a change to day work among the
      shift workers who remained in the organization during the entire follow-up
      period. CONCLUSIONS: Employees with several risk factors are more likely to leave
      an organization regardless of the type of work schedule. Health-related selection
      out of shift work is an unlikely source of major bias in research on shift work
      and CVD.

PMID- 16804624
TI  - Development of a questionnaire to assess worker knowledge, attitudes and
      perceptions underlying dermal exposure.
AB  - OBJECTIVES: Workers' behavior is identified as an important determinant of dermal
      exposure and is influenced by knowledge, attitudes, and risk perceptions. Because
      behavior may be a significant predictor of exposure, its assessment provides a
      means for examining exposure and designing strategies and incentives that
      encourage worker protective behavior. Currently, there are no psychosocial
      instruments examining worker knowledge, attitudes, and perceptions with respect
      to dermal hazards. Accordingly, a questionnaire was developed and tested to
      provide an instrument for measuring worker knowledge, attitudes, and perceptions.
      METHODS: The questionnaire was developed on the basis of a literature review and
      expert consultation. Scales were constructed based on standard methods. Two
      worker focus groups were used to evaluate worker understanding and content
      validity of the KAP (knowledge, attitudes, perceptions) questionnaire. The
      resulting 115-item questionnaire that included scales for knowledge (N=13),
      attitudes (N=27), perceptions (N=15), behavior (N=8), behavioral intentions
      (N=15), barriers (N=13), and facilitators (N=5) was tested on 89 workers from 19
      facilities. RESULTS: The concepts identified in the focus groups included worker
      perception of higher risk due to a poor fit and replacement frequency for
      personal protective equipment and cross-contamination by workers moving into work
      zones. Field testing of the questionnaire (N=89) yielded Cronbach's alpha
      reliability scores ranging from 0.87 for the self-efficacy personal protective
      equipment scale to 0.92 for the overall belief scale, indicating high internal
      reliability. CONCLUSIONS: Although further testing and refinement is needed, this
      survey instrument provides an initial and conceptually unique means for
      evaluating behavioral determinants of worker dermal exposure.

PMID- 16804625
TI  - Occupational skin exposure and hand eczema among dental technicians-need for
      improved prevention.
AB  - OBJECTIVES: The aims of this study were to estimate occupational skin exposure,
      the use of skin protection, and the incidence of hand eczema among dental
      technicians. METHODS: In a retrospective cohort study, dental technicians
      (N=2139) and randomly selected population controls (N=2288) received a postal
      questionnaire on occupational skin exposure, protective glove use, and hand
      eczema, including the year of onset. The response rate was 57% for the dental
      technicians and 58% for the controls. RESULTS: Altogether 80% of the dental
      technicians reported skin exposure to uncured (meth)acrylates (MA), and 87% had
      skin contact with grinding dust from MA. Thirty-nine percent used protective
      gloves when handling uncured MA. Twenty-two percent of the currently employed
      technicians reported participation in obligatory training concerning the handling
      of thermosetting plastics, and 58% did not know how long normally used gloves
      protected the skin against uncured MA. Altogether 48% of the dental technicians
      and 30% of the controls reported more than 10 hand washings a day (P<0.001). For
      the dental technicians, the incidence of hand eczema was 8.5 cases/1000 person
      years during MA-exposed time. For the controls, the incidence was 3.3. The
      incidence rate ratio for the men was 3.6 (95% CI 2.3-5.6), and for the women it
      was 2.4 (95% CI 1.7-3.3). CONCLUSIONS: The work of dental technicians involves
      frequent and unprotected exposure to MA and frequent hand washings. Dental
      technicians have twice the risk of hand eczema than the general population.
      Efforts to improve skin protection and increase participation in obligatory
      training about handling thermosetting plastics are important.

PMID- 16804626
TI  - Tape-strip sampling for measuring dermal exposure to 1,6-hexamethylene
      diisocyanate.
AB  - OBJECTIVES: This study describes the development and evaluation of a method for
      sampling layers of the stratum corneum for the quantitation of dermal exposure to
      1,6-hexamethylene diisocyanate (HDI). METHODS: HDI deposited on skin was
      collected by the removal of stratum corneum with adhesive tape, derivatized with
      1-(2-methoxyphenyl)piperazine, and quantitated as the urea derivative (HDIU) by
      liquid chromatography-mass spectrometry (LC-MS). This LC-MS method was tested by
      analyzing tape spiked with HDI-containing products, then applied to tape samples
      collected from the skin of an auto-body shop worker exposed to polyurethane paint
      aerosols. RESULTS: The limits of detection and quantitation were 20 and 50 fmol
      per injection, respectively. The recovery of HDI from the tape was 99.3% [95%
      confidence interval (95% CI) 97.1-102]. HDIU was stable at -40 degrees C,
      degrading by 0.28% (95% CI 0.10-0.46) per day. Quantifiable amounts of HDI were
      observed in 42.6% of the first three successive tape-strip samples collected from
      36 different sites on the skin of the worker. The amount of HDI recovered from
      the collection sites on skin, measured by summing the levels collected with three
      successive tape-strips, ranged from nondetectable to 1874 pmol. CONCLUSIONS: This
      study demonstrates that HDI on skin can be collected with tape-strips and
      quantified at occupational levels using LC-MS.

PMID- 16804627
TI  - Nonstandard shift schedules and the risk of job-related injuries.
AB  - OBJECTIVES: This study assessed the extent to which working various types of
      nonstandard shift schedules (eg, night and evening shifts) is associated with the
      risk of occupational injuries or illnesses. METHODS: Multivariate analyses were
      conducted using data from 13 years (1987 to 2000) of the National Longitudinal
      Survey of Youth (NLSY) encompassing 110 236 job records and over 82 000 person
      years of work experience. Cox proportional hazard regression techniques were used
      to derive hazard ratios comparing the relative risk of suffering a work-related
      injury among people working night, evening, rotating, split, and irregular shifts
      to the risks for those working conventional day shifts, after adjustment for age,
      gender, occupation, industry, and region. Incidence rates were normalized using a
      common denominator of 100 person-years of "at-risk time" to obtain valid
      comparisons. RESULTS: All of the nonstandard shift schedules, except split
      shifts, were found to have a higher risk for occupational injuries and illnesses
      than conventional day shifts. After control for the selected covariates, the
      calculated hazard ratios were 1.43 for evening shifts [95% confidence interval
      (95% CI) 1.26-1.62], 1.36 for rotating shifts (95% CI 1.17-1.58), 1.30 for night
      shifts (95% CI 1.12-1.52), 1.15 for irregular shifts (1.03-1.30), and 1.06 for
      split shifts (0.71-1.58). CONCLUSIONS: These findings suggest that nonstandard
      shifts are not more risky merely because of the concentration of hazardous jobs
      in those types of schedules or because of underlying differences in the
      characteristics of employees working nonstandard shifts. The results point to the
      need to extend targeted injury prevention programs not only to people working
      night shifts, but also to those who work evenings.

PMID- 16804628
TI  - Renal function of chloralkali workers after the cessation of exposure to mercury
      vapor.
AB  - OBJECTIVES: The aims of the study were to assess renal function in chloralkali
      workers previously exposed to mercury vapor and to assess the impact of selenium
      status on the biomarkers of kidney function. METHODS: Forty-nine chloralkali
      workers previously exposed to mercury vapor were compared with 49 age-matched
      referents in a cross-sectional study. Selected biomarkers of kidney function and
      biomarkers of selenium status were measured. The index group had been exposed for
      13.1 (range 2.8-34.5) years on the average at a mean urinary mercury excretion of
      9.3 (range 4.0-25.4) nmol/mmol creatinine a year. The exposure had ceased on an
      average of 4.8 (range 4.2-10.0) years prior to the examinations. RESULTS: No
      statistically significant differences were found between the groups for the
      measured biomarkers of kidney function. The serum selenium concentration and
      serum glutathione peroxidase activity were associated with the activity of N
      acetyl-beta-D-glucosaminidase in urine (U-NAG). The results indicate that having
      higher glutathione peroxidase activity or a higher serum selenium concentration
      results in a lower excretion of U-NAG. This effect was the most pronounced in the
      oldest third of the participants. Apparently the well-known association between U
      NAG and age could only be found for the participants with a lower selenium
      status. CONCLUSIONS: Increased activities of U-NAG during ongoing exposure to
      mercury vapor appear to be reversible upon cessation of exposure. Selenium status
      has a substantial impact on U-NAG activity and should be considered in studies of
      U-NAG excretion.

PMID- 16804629
TI  - Involvement of central airways in vibroacoustic disease patients.
AB  - INTRODUCTION: Vibroacoustic disease (VAD) is the whole-body pathology caused by
      excessive exposure to LFN. For the past 25 years, it has been know that low
      frequency noise (LFN, < 500 Hz, including infrasound) targets the respiratory
      system. In LFN-exposed rodents, the morphological changes of respiratory tract
      tissue partially explained some respiratory symptoms reported by VAD patients.
      However, many questions remain unanswered. Recently, some volunteer VAD patients
      underwent bronchoscopy in order to ascertain possible damage that could be
      associated with their respiratory complaints. METHODS: Fourteen fully-informed
      and volunteer VAD patients were submitted to bronchoscopy, and biopsies were
      removed for analysis. RESULTS: All patients exhibited small submucosal vascular
      like lesions near the spurs, consisting of increased collagen and elastin fibres.
      Histology disclosed cilliary abnormalities, basal membrane hyperplasia, and
      thickening of vessel walls. In five patients, collagen bundles appeared
      degenerative and disrupted. No inflammatory process was ever identified, and no
      differences were seen between smokers and non-smokers. DISCUSSION: Data is in
      accordance with what was observed in LFN-exposed animal models and also in 8 VAD
      patients who developed lung tumours. Collagen disruption and degeneration was
      also observed in electron microscopy images of the respiratory tract of LFN
      exposed rodents. Thickened blood and lymphatic vessel walls have been
      consistently seen in images of VAD patients and of LFN-exposed rodents. During
      bronchoscopy performed by other reasons, this sort of structural aspects is not
      frequently seen. Taken together, it is strongly suggested that these findings
      could be VAD-specific.

PMID- 16804630
TI  - [Specific immunotherapy effect on peripheral blood T1/T2 lymphocytes in atopic
      patients].
AB  - Allergen-specific immunotherapy has been used for successful treatment of atopic
      diseases. They may act by modifying the patterns of cytokines produced by T
      cells. However, the precise mechanism by which it accomplishes these effects is
      still incompletely understood. OBJECTIVE: To evaluate the effect of one year
      immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in
      atopic patients. METHODS: We studied 10 atopic patients sensitised to common
      environmental allergens receiving immunotherapy over one year mean period. Six of
      these patients were studied before and after immunotherapy. Fourteen atopic
      patients untreated and 7 non-atopic subjects were used as control groups.
      Intracellular cytokine production (IFN-g; IL-4; IL-5; IL-10) was determined by
      flow cytometry following stimulation with phorbol myristate acetate (PMA),
      ionomycin and brefeldin. Mann-Whitney U and Wilcoxon non-parametric tests were
      utilized for the statistical analysis. RESULTS: The expression of IL-4 and IL-5
      in T cells, characteristically increased in atopic patients, respectively 13.8
      (3.1 - 31.8) and 6.7% (1.0 -20.4), was significantly lower in the immunotherapy
      group [5.4 (2.9 -15.6) p=0.007 and 2.1% (0,6 - 4.8) p=0.035] and similar in the
      non-atopic control group. The levels of IFN-g did not differ between the studied
      groups but the ratio IFN-g / IL-4 produced by CD4+ T lymphocytes increased
      significantly in the patients receiving immunotherapy. In addition, there was an
      increase in the expression of IL-10 by T cells of the immunotherapy group
      compared to the non-atopic controls [1.9 (1.0 - 4.9) versus 1.4% (0.9 - 1.4)
      p=0.02], being more evident in CD8+ T lymphocytes. IL-10 correlated significantly
      with all the profile T2 cytokines (IL-4 and IL-5) and with the phenotype Tc2.
      CONCLUSION: After one year of immunotherapy the peripheral T cells response to a
      polyclonal stimulation revealed a reduction in IL-4 and IL-5 production,
      characteristically increased in atopic disease. The increase of IL-10 that we
      found in our study suggested the existence of a profile T2 regulatory population,
      more evident in CD8+T lymphocytes.

PMID- 16804631
TI  - [Cardiac influence on mechanical ventilation time and mortality in exacerbated
      chronic respiratory failure patients. The role of echocardiographic parameters].
AB  - OBJECTIVE: To study the influence of cardiac status on the length of mechanical
      ventilation, outcome and disease severity in patients admitted to an Intensive
      Care Unit (ICU) with exacerbation of chronic respiratory failure. DESIGN AND
      SETTING: A 30-month prospective study in a 14 bed ICU PATIENTS AND METHODS: Fifty
      nine patients were enrolled, with a mean age 74.7 +/- 9.7 years, mean length of
      ventilator support 10.8 +/- 12.6 days, and mean APACHE II score 23 +/- 8.3.
      Within the first 24 hours of admittance, cardiac chamber dimensions, inferior
      vena cava (IVC), and mitral transvalvular Doppler were evaluated using
      transthoracic echocardiography; the cardiac rhythm was recorded (presence of
      sinus rhythm or atrial fibrillation). Blood gases were evaluated at discharge.
      RESULTS: Greater length of ventilation was observed in patients presenting atrial
      fibrillation (p=0.027), particularly when a dilated IVC was also present (>20mm,
      p=0.004). A high level of serum bicarbonate (>35 mEq/l), was also related with
      longer ventilation (p=0. 04). Twelve patients died. Mortality was related to the
      presence of a dilated right ventricle (p=0. 03) and a ratio between right and
      left ventricle> 0. 6 (p=0.04). CONCLUSION: Patients submitted to mechanical
      ventilation due to exacerbation of chronic respiratory failure which present
      atrial fibrillation require a longer ventilation period, particularly if a
      dilated IVC is also present. Patients with dilated right cardiac chambers are at
      an increased risk of a fatal outcome.

PMID- 16804632
TI  - [Impact of sleep hygiene on patients with obstructive sleep apnoea syndrome].
AB  - The purpose of this study was to evaluate the impact of a Sleep Hygiene brochure
      on a population of 36 patients recently diagnosed with Obstructive Sleep Apnoea
      Syndrome and beginning treatment. One expects that: 1) the information about
      Sleep Hygiene offered in the brochure would change some of the patients' habits
      toward sleep; and that, 2) this intervention in the form of a free informative
      brochure would have an echo in terms of a better subjective evaluation of sleep
      complaints. The sleep habits and the sleep complaints were evaluated in the pre
      test. Those variables were re-evaluated in the post-test and at that time the
      patients filled in a scale of satisfaction with the information about Sleep
      Hygiene, in terms of its contribution to improving their sleep complaints. There
      were no significant differences in the level of compliance to Sleep Hygiene
      between the two periods, although the majority of the patients considered that
      Sleep Hygiene did improve their sleep difficulties. The low level of compliance
      may be due to the fact that patients already had reasonable Sleep Hygiene habits,
      and also to the fact that the scale was not sufficiently discriminative. In
      addition, the self-discipline that Sleep Hygiene involves may have collided with
      other demands such as the adaptation to treatment with CPAP (Continuous Positive
      Air Pressure). In a following study, it would be interesting to find if the
      levels of sleep hygiene compliance would change if they were implemented after
      the initial adaptation to CPAP, which would imply a longitudinal study. It would
      be helpful to keep reminding the patients of Sleep Hygiene importance, offering
      new and update brochures to the patients during consultations.

PMID- 16804633
TI  - [Pleomorphic adenoma of the trachea. Case report].
AB  - The authors present a case of a pleomorphic adenoma of the trachea, diagnosed
      during the clinical evaluation of a suspected COPD or lung cancer in a heavy
      smoker patient with a positive family history of oncologic diseases. The patient
      underwent segmental resection of the trachea with complete excision of the
      tumour, and a good prognosis is anticipated.

PMID- 16804634
TI  - Elevated postvoid residual in women with pelvic floor disorders: prevalence and
      associated risk factors.
AB  - A retrospective case-control study was designed to assess risks for elevated post
      void residual (PVR) in women with pelvic floor disorders. The 1,399 women
      underwent evaluation including standardized questionnaire, examination, and
      catheterized PVR. Elevated PVR was defined as > or =100 ml and anterior and
      apical prolapse was defined as at or beyond the hymen. Overall, the prevalence of
      elevated PVR was 11%. After matching, the absence of stress incontinence symptoms
      (OR 0.55, CI 0.33-0.92), the symptoms of vaginal bulge (OR 2.19, CI 1.38-3.48),
      pelvic pressure (OR 1.79, CI 1.14-2.86), urinary splinting (OR 2.89, CI 1.24
      6.74), and presence of prolapse (OR 2.60 CI 1.62-4.18) were significantly
      associated with an elevated PVR. Only prolapse (OR 1.96 CI 1.37-2.79) maintained
      a significant association after multivariate analysis. Symptoms alone do not
      predict which women may have an elevated PVR, but the finding of prolapse at or
      beyond the hymen is associated with incomplete emptying. Elevated post void
      residuals cannot be predicted based on symptoms alone; however, prolapse beyond
      the hymen may help identify women with incomplete bladder emptying.

PMID- 16804635
TI  - Sacral neuromodulation and lower urinary tract dysfunction in cerebral palsy.
AB  - Given the emerging role of sacral neuromodulation in treatment of neurogenic
      voiding dysfunction, the author describes the use of sacral neuromodulation in a
      patient with voiding dysfunction caused by cerebral palsy (CP). A 45-year-old
      patient with cerebral palsy presented with progressive complaints of urgency and
      overflow incontinence and was found to be in retention. She underwent sacral
      neuromodulation and had complete resolution of her symptoms. The literature of
      lower urinary tract dysfunction in CP is reviewed. It is concluded that sacral
      neuromodulation may be a valuable tool in treating storage and voiding disorders
      associated with CP.

PMID- 16804636
TI  - Outcome measures in urogynaecology: the clinicians' perspective.
AB  - There is currently a paucity of information regarding clinicians' expectations of
      treatment and whether their perception of bothersome symptoms is similar to that
      of the patient. Equally there is often a dichotomy of opinion when comparing
      clinician-centered evaluation with that of patients. The objectives of this study
      were to determine clinicians' expectations following treatment, to assess the
      methods of outcome assessment used in the clinical and research settings, and to
      compare clinician's expectations with those of patients. This was a prospective
      postal questionnaire-based study sent to members of the International Continence
      Society (UK). The questionnaire asked about expectations following treatment and
      use of outcome measures. These results were also compared to those of an
      identical patient questionnaire that have previously been published. Tests of
      agreement were performed between clinicians and patients using Cohen's kappa
      statistic. Two hundred ninety-nine questionnaires were distributed with a
      response rate of 52.7%. Overall, 85.9% of responding clinicians felt a good
      improvement in urinary symptoms, so that they no longer interfered with quality
      of life, was a realistic outcome. The majority of clinicians thought that small
      or infrequent episodes of leakage were acceptable following treatment, although
      frequent or large leaks were not. Irritative urinary symptoms such as urgency and
      urge incontinence were felt to be less acceptable as were the symptoms of
      frequency and nocturia. Overall, there was found to be poor agreement between
      clinicians and patients attitudes to acceptability of symptoms with values of
      kappa ranging from -0.103 to 0.105, indicating that this agreement was no better
      than chance. In the research setting, 61% felt both subjective and objective
      outcome measures should be used, whereas in clinical practice, 42% thought
      subjective improvement alone, and 36% subjective improvement in QoL, were
      appropriate. Clinicians have realistic expectations following treatment, although
      there is poor agreement with those expectations expressed by patients. These
      findings may help to explain why patients may be disappointed regarding treatment
      outcomes and why there may be a difference between subjective clinical impression
      of success and patient satisfaction. In addition there is a lack of conformity in
      the use of outcome measures in both the clinical and research settings.

PMID- 16804637
TI  - Anti-amyloidogenic therapies: strategies for prevention and treatment of
      Alzheimer's disease.
AB  - Deposition of amyloid beta-protein (Abeta) in the brain is an early and invariant
      neuropathological feature of Alzheimer's disease (AD). The current search for
      anti-AD drugs is mainly focused on modification of the process of accumulation of
      Abeta in the brain. Here, we review four anti-amyloidogenic strategies: (i)
      reduction of Abeta production, which has mainly been approached with secretase
      inhibition, (ii) promotion of the Abeta degrading catabolic pathway, including an
      Abeta degrading enzyme, neprilysin, (iii) immunotherapy for Abeta and (iv)
      inhibition of Abeta aggregation. We have reported that AD patients have a
      favorable molecular environment for Abeta aggregation and that various compounds,
      such as polyphenols, interfere with Abeta aggregation and destabilize preformed
      Abeta fibrils.

PMID- 16804638
TI  - Biological effects of stevioside on the survival of Escherichia coli strains and
      plasmid DNA.
AB  - Stevioside is widely used daily in many countries as a non-caloric sugar
      substitute. Its sweetening power is higher than that of sucrose by approximately
      250-300 times, being extensively employed as a household sweetener, or added to
      beverages and food products. The purpose of this study was to ascertain
      stevioside genotoxic and cytotoxic potentiality in different biological systems,
      as its use continues to increase. Agarose gel electrophoresis and bacterial
      transformation were employed to observe the occurrence of DNA lesions. In
      addition to these assays, Escherichia coli strains were incubated with stevioside
      so that their survival fractions could be obtained. Results show absence of
      genotoxic activity through electrophoresis and bacterial transformation assays
      and drop of survival fraction of E. coli strains deficient in rec A and nth
      genes, suggesting that stevioside (i) is cytotoxic; (ii) could need
      metabolization to present deleterious effects on cells; (iii) is capable of
      generating lesions in DNA and pathways as base excision repair, recombination and
      SOS system would be important to recover these lesions.

PMID- 16804639
TI  - Manufacturing consensus.
AB  - The Food and Drug Administration (FDA) has declared that it would be illegal to
      advertise as or in any way claim your drug to be superior to competitors on the
      market, which are up to 30 times cheaper. How does a pharmaceutical company
      market such a product? The answer is to enlist academics to form expert panels to
      construct guidelines and algorithms, or participate in Delphi panels and other
      exercises, which can be expected to prove that newer, more costly drugs produce
      cost savings. These academics do so on the basis of the existing clinical trial
      evidence--which supposedly the FDA has used to come to its verdict that the newer
      compound is no better than its competitors. However, where the FDA has seen the
      raw data, academics later see the published data. In between intervenes a medical
      writing exercise, which produces the first and most important piece of
      advertising for any pharmaceutical product--the randomized controlled trial
      infomercial. This paper explores how pharmaceutical companies manufacture an
      apparent academic consensus and, in so doing, gives a case study of the recent
      controversies surrounding the marketing of selective serotonin reuptake inhibitor
      (SSRI) drugs for adolescent depression.

PMID- 16804640
TI  - Frequency and prognosis of delayed facial palsy after microvascular decompression
      for hemifacial spasm.
AB  - BACKGROUND: Microvascular decompression (MVD) for hemifacial spasm (HFS) provides
      a long-term cure rate. Delayed facial palsy (DFP) is not an unusual complication,
      but it has only been sporadically described in the literature. The purpose of
      this report is to evaluate the incidence of delayed facial palsy after MVD and
      its clinical course and final results. METHODS: From January, 1998 to April,
      2004, 410 patients underwent microvascular decompression for hemifacial spasm at
      our Institute. During this time, 21 patients (5.4%) developed delayed facial
      weakness; eighteen of them were given steroid medication and they were followed
      up in the out-patient clinic. FINDINGS: Twenty-one patients developed DFP after
      microvascular decompression an incidence of 5.4%. There were seventeen women
      (81.0%) among the 21 patients with DFP who were included in this study. In twenty
      of them, the symptoms of HFS improved completely after the operation, but the
      spasm remained with one of them. The onset of palsy occurred between
      postoperative day 7 and 23 (average: 12.1 days). The palsy was at least Grade II
      or worse on the House-Brackmann (HB) scale. The time to recovery averaged 5.7
      weeks (range: 25 days-17 weeks); 20 patients improved to complete recovery and 1
      patient remained with minimal weakness, as Grade II on the HB scale, at the
      follow-up examination. CONCLUSION: Our findings demonstrated that the incidence
      of DFP was not so low as has been reported the literature, and it did not have
      any striking predisposing factors. Even though the degree of facial palsy was
      variable, almost all patients exhibited a complete recovery without any further
      special treatment. The etiology of DFP and its association with herpes infection
      should be further clarified.

PMID- 16804641
TI  - Thoracic radiculopathy from a paravertebral mesothelial cyst.
AB  - We report on an extremely rare case of a paravertebral thoracic mesothelial cyst
      in a young woman who presented with dorsal radiculopathy affecting the T5
      dermatome. The patient underwent a standard transthoracic intercostal approach
      with removal of the cyst. During the operation, the T5 intercostal neurovascular
      bundle was found firmly attached to the lesion elucidating the origin of the
      radicular pain. To our knowledge, this is the first report of radiculopathy due
      to a paravertebral mesothelial cyst. Although highly unusual, paravertebral
      mesothelial cyst should be considered in the differential diagnosis for lesions
      inducing dorsal radicular pain.

PMID- 16804642
TI  - Small keyhole transuncal foraminotomy for unilateral cervical radiculopathy.
AB  - Interbody fusion after anterior discectomy may lead to acceleration of
      degenerative changes at adjacent levels. Although the posterior approach
      preserves the motion segment, decompression of the nerve root is indirect if
      "hard disc prolaps" is the main cause. Recently, a technique of microsurgical
      anterior cervical foraminotomy for the treatment of radiculopathy with
      preservation of the segment mobility was published. In this study, we present
      this technique with several modifications.Thirteen patients - 5 men and 8 women
      with an average age of 49 years - with unilateral radiculopathy resistant to
      conservative treatment underwent microsurgical anterior foraminotomy via a small
      keyhole transuncal approach. The base of the uncinate process (UP) was directly
      drilled in the trajectory to the intervertebral foramen without destroying the
      disc tissue. The vertebral artery between the transverse process was not exposed.
      Furthermore, the functional anatomy of the uncovertebral joint remained largely
      intact. All patients experienced complete relief of radiating pain. A cervical
      collar was not used. Mean follow-up time was 19 months. The mobility of the
      operated segment was preserved in each patient. No instability of the cervical
      spine was seen. The microsurgical anterior foraminotomy via a small keyhole
      transuncal approach is safe, minimally invasive, and represents an effective
      method to treat unilateral cervical radiculopathy caused by disc prolaps and/or
      uncovertebral osteophytes. Additionally, the segment mobility is preserved and
      prevents the acceleration of degenerative changes at adjacent levels.

PMID- 16804643
TI  - Micro-vascular decompression for primary Trigeminal Neuralgia (typical or
      atypical). Long-term effectiveness on pain; prospective study with survival
      analysis in a consecutive series of 362 patients.
AB  - BACKGROUND: Few publications on primary Trigeminal Neuralgia treated by Micro
      Vascular Decompression (MVD) report large series, with long-term follow-up, using
      Kaplan-Meier (K-M) analysis. None was specifically directed to the comparative
      study of MVD effectiveness on Trigeminal Neuralgia with typical (i.e., with
      paroxysmal pain only) and atypical features (i.e., with association of a
      permanent background of pain). METHOD: The authors report a series of 362
      patients having clearcut vascular compression and treated with pure MVD - i.e.,
      without any additional cut or coagulation of the adjacent root fibers. Follow-up
      was 1 to 18 y (8 y on average, with a median of 7.2 y). Results were considered
      overall, then separately for patients with typical (237 (65.5%)) and atypical
      (125 (34.5%)) clinical presentation. FINDINGS: One year after operation, (294
      (81.2%) of patients were totally-free - of paroxysmal pain, and also of permanent
      background pain - and not needing any medication) 13 (3.6%) still had a
      background of pain but without the need for medication which 55 patients (15.2%),
      treatment had failed. At latest review (8 y on average) the corresponding rates
      were 80, 4.9 and 15.1%, respectively. Kaplan-Meier analysis estimated the
      probability of total cure at 15 y to be 73.4%. There was no difference in the
      cure rate between patients with typical and atypical features at one year: 81 and
      81.16%, respectively. The probability of cure at 15 y was identical for the two
      clinical presentations. CONCLUSIONS: Pure MVD offers patients affected by
      Trigeminal Neuralgia due to vascular compression a long-lasting cure in three
      fourths of the cases. Both typical and atypical presentations respond well to
      MVD, view in contrast to the classical view that an atypical presentation has an
      adverse effect on outcome after surgery.

PMID- 16804644
TI  - Cerebellar haemorrhage after non-traumatic evacuation of supratentorial chronic
      subdural haematoma: report of two cases.
AB  - Cerebellar haemorrhage is an unusual complication of supratentorial neurosurgery.
      Several causative pre-operative factors and medical risk factors may predispose
      patients to cerebellar haemorrhage, however its etiology remains still unclear.
      Only two case reports have previously described the occurrence of cerebellar
      haemorrhage after subdural haematoma evacuation by burr-hole trepanation. We
      present two patients with this rare postoperative complication of minor
      supratentorial neurosurgery and possible underlying pathophysiological mechanisms
      are discussed. Our two cases support the post- rather than per-operative
      pathogenetic hypothesis. Although the complication is associated with a
      significant morbidity and mortality, most cases follow a benign course.

PMID- 16804646
TI  - Kinetic tremor in Parkinson's disease--an underrated symptom.
AB  - Since the first description of the disorder which we now call "Parkinson's
      Disease" (PD) much has changed not only because of new therapeutic possibilities.
      Initially only the rest tremor was described. Today it is generally accepted that
      PD can be accompanied by different forms of tremor. Nevertheless the kinetic
      tremor is hardly examined and no attention is paid to it in clinical rating
      scales although it can already be found in old published drawings of PD-patients.
      To date instrumented investigations do not capture the most common kinetic tremor
      of PD that seems to be frequent under everyday life conditions. In order to
      assess the significance of kinetic tremor in PD, tremor during a spiral drawing
      task was investigated in an open study involving 870 patients. The results
      indicate that a combination of rest, postural and kinetic tremors constitute the
      most frequent tremor constellation in PD.

PMID- 16804647
TI  - Supply of human allograft tissue in Canada.
AB  - There is relatively little known about the supply for allograft tissues in
      Canada. The major aim of this study is to quantify the current or "Known Supply"
      of human allograft tissue (bone, tendons, soft tissue, cardiovascular, ocular and
      skin) from known tissue banks in Canada, to estimate the "Unknown Supply" of
      human allograft tissue available to Canadian users from other sources, and to
      investigate the nature and source of these tissue products. Two surveys were
      developed; one for tissue banks processing one or more tissue types and the other
      specific to eye banks. Thirty nine sites were initially identified as potential
      tissue bank respondent sites. Of the 39 sites, 29 sites indicated that they were
      interested in participating or would consider completing the survey. A survey
      package and a self-addressed courier envelope were couriered to each of 29 sites.
      A three week response time was indicated. The project consultants conducted
      telephone and email follow-up for incomplete data. Unknown supply was estimated
      by 5 methods. Twenty-eight of 29 sites (97%) completed and returned surveys. Over
      the past year, respondents reported a total of 5,691 donors (1,550 living and
      4,141 cadaveric donors). Including cancellous ground bone, there were 10,729
      tissue products produced by the respondent banks. Of these, 71% were produced by
      accredited banks and 32% were ocular tissues. Total predicted shortfall of
      allograft tissues was 31,860-66,481 grafts. Through estimating Current supply,
      and compiling additional qualitative information, this study has provided a
      snapshot of the current Canadian supply and shortfall of allograft tissue grafts.

PMID- 16804648
TI  - Demand for human allograft tissue in Canada.
AB  - There is relatively little known about the demand for allograft tissues in
      Canada. The Canadian Council for Donation and Transplantation (CCDT) is a
      national advisory body that undertook a comprehensive "market survey" to estimate
      surgical demand for human allograft tissues in Canada. The report "Demand for
      Human Allograft Tissue in Canada" reflects survey results sent to 5 prominent
      User Groups. User Groups were identified as orthopaedic surgeons; neurosurgeons;
      corneal transplant surgeons; plastic surgeons, specifically those at Canadian
      Burn Units; and cardiac surgeons (adult and paediatric surgery). The demand for
      allograft grafts was determined and then extrapolated across the total User Group
      and then increases in allograft tissue use over the next 1-2 years across User
      Groups were predicted. The overall response rate for the survey was 21.4%. It
      varied from a low of 19.6% for the orthopaedic survey to a high of 40.5% for the
      corneal survey. The estimated current demand for allograft tissue in Canada
      ranges from a low of 34,442 grafts per year to a high of 62,098 grafts per year.
      The predicted increase in use of allograft tissue over the next 1-2 year period
      would suggest that annual demand could rise to somewhere in the range of 42,589
      72,210 grafts. The highest rated preferences (98% and 94%) were for accredited
      and Canadian tissue banks, respectively. This study represents a key step in
      addressing the paucity of information concerning the demand for allograft tissue
      in Canada.

PMID- 16804649
TI  - The use of irradiated allograft in a paediatric population: an Indian experience.
AB  - Lyophilised, irradiated bone allografts available for the first time in the
      country from the Tata Memorial Hospital Tissue Bank were used in 30 paediatric
      patients from January 2001 to August 2004. They included 20 patients of scoliosis
      of various origin and ten with assorted orthopaedic conditions including one
      congenital kyphosis, two Pott's spine, one Perthes disease, one developmental
      dysplasia of the hip (DDH), one infective non-union, one fibrous dysplasia and
      three with bone defects either due to trauma, a cyst or removal of hardware.
      Morsellised allograft was used in 28 patients. In those cases of scoliosis in
      which ribs were resected out during costectomy, the morsellised allograft was
      mixed with morsellised rib autograft. Non-morsellised femoral head grafts were
      used in two patients, one a case of varus open derotation osteotomy in Perthes
      disease and the other an acetabuloplasty in DDH. Patients were followed at
      intervals of 8-12 weeks and radiological evaluation was done periodically. The
      follow up period ranged from 1 to 4 years post surgery. All patients with
      scoliosis showed excellent union at the grafting site with non-progression of
      curve and no signs of loosening at implant site. The two patients, in whom non
      morsellised femoral head grafts were used, both showed incorporation of the graft
      with good fusion within a 4 month period. None of the patient had infection, non
      union, pseudoarthrosis, fracture at the graft site, or any other complication.

PMID- 16804650
TI  - Competing effects of toxin-producing phytoplankton on overall plankton
      populations in the bay of Bengal.
AB  - The coexistence of a large number of phytoplankton species on a seemingly limited
      variety of resources is a classical problem in ecology, known as 'the paradox of
      the plankton'. Strong fluctuations in species abundance due to the external
      factors or competitive interactions leading to oscillations, chaos and short-term
      equilibria have been cited so far to explain multi-species coexistence and
      biodiversity of phytoplankton. However, none of the explanations has been
      universally accepted. The qualitative view and statistical analysis of our field
      data establish two distinct roles of toxin-producing phytoplankton (TPP): toxin
      allelopathy weakens the interspecific competition among phytoplankton groups and
      the inhibition due to ingestion of toxic substances reduces the abundance of the
      grazer zooplankton. Structuring the overall plankton population as a combination
      of nontoxic phytoplankton (NTP), toxic phytoplankton, and zooplankton, here we
      offer a novel solution to the plankton paradox governed by the activity of TPP.
      We demonstrate our findings through qualitative analysis of our sample data
      followed by analysis of a mathematical model.

PMID- 16804651
TI  - A theoretical and experimental study of competition between solution and surface
      receptors for ligand in a Biacore flow cell.
AB  - Rate constants that characterize the kinetics of binding and dissociation between
      biomolecules carry fundamental information about the biological processes these
      molecules are involved in. An instrument that is widely used to determine these
      rate constants is the Biacore. In a Biacore experiment, one of the reactants,
      which we will call the receptor, is immobilized on a sensor chip. During the
      binding phase of the experiment the other reactant flows past the chip. After
      binding, buffer alone is introduced into the flow cell and dissociation is
      monitored. Often surface-based binding assays are influenced by the transport of
      the reactant in solution, complicating the determination of the chemical rate
      constants from the observed binding kinetics. We propose a new way to determine
      the dissociation rate constant by adding soluble receptor during dissociation.
      The method is tested first on simulated data and then on Biacore experiments
      where the lac repressor protein binds and dissociates from a stretch of double
      stranded DNA containing the lac repressor binding site. With this method we find
      a dissociation rate constant k(d)=0.075 +/- 0.005s(-1), a value that is faster
      than previously obtained from Biacore experiments. In developing our method to
      analyze these experiments we obtain an expression for the transport limited rate
      constant for a Biacore experiment when soluble receptor is present during
      dissociation.

PMID- 16804652
TI  - A viscoelastic traction layer model of muco-ciliary transport.
AB  - A new mathematical model of the transport of mucus and periciliary liquid (PCL)
      in the airways by cilia is presented. Mucus is represented by a linearly
      viscoelastic fluid, the mat of cilia is modelled as an 'active porous medium.'
      The propulsive effect of the cilia is modelled by a time-dependent force acting
      in a shear-thinned 'traction layer' between the mucus and the PCL. The effects of
      surface and interface tension are modelled by constraining the mucus free surface
      and mucus-PCL interface to be flat. It is assumed that the epithelium is
      impermeable to fluid. Using Fourier series, the system is converted into ODEs and
      solved numerically. We calculate values for mean mucus speed close to those
      observed by Matsui et al. [J. Clin. Invest., 102(6):1125-1131, 1998],
      (approximately 40 microm s(-1)). We obtain more detail regarding the dynamics of
      the flow and the nonlinear relationships between physical parameters in healthy
      and diseased states than in previously published models. Pressure gradients in
      the PCL caused by interface and surface tension are vital to ensuring efficient
      transport of mucus, and the role of the mucus-PCL interface appears to be to
      support such pressure gradients, ensuring efficient transport. Mean transport of
      PCL is found to be very small, consistent with previous analyses, providing
      insight into theories regarding the normal tonicity of PCL.

PMID- 16804653
TI  - MRSA decolonization--is it feasible?

PMID- 16804654
TI  - A prospective, randomized multicenter trial of the empirical addition of
      antifungal therapy for febrile neutropenic cancer patients: results of the Paul
      Ehrlich Society for Chemotherapy (PEG) Multicenter Trial II.
AB  - BACKGROUND: The aim of the study was to compare the efficacy of empirical
      antifungals in combination with broad spectrum antibiotics with that of
      antibiotics alone in high risk febrile neutropenic cancer patients not responding
      to initial antibacterial therapy. PATIENTS AND METHODS: A prospective, randomized
      controlled trial was conducted at 22 cancer centers in Germany. Patients with
      fever of unknown origin were randomized to either piperacillin (Pip) plus an
      aminoglycoside (AMG) (arm A) or a third generation cephalosporin (Ceph) plus AMG
      (arm B). Patients not responding after 4-6 days were randomized to either
      imipenem (Imi) plus glycopeptide (GLP) (arm C), or Imi/GLP plus amphotericin B
      deoxycholate (AmB) plus 5-flucytosine (5-FC) (arm D), or Imi/GLP plus fluconazole
      (Fluco) (arm E). A successful outcome was defined as resolution of fever.
      RESULTS: In arm A, 192 of 373 patients (51.5%) responded as compared to 176 of
      344 patients (51.2%) in arm B. The response rates of 155 patients randomized for
      further empirical treatment were 55.6%, 77.8% and 62.5% in arm C, D and E,
      respectively. The difference between arm C and D was of borderline statistical
      significance (p = 0.06) after correction for multiple testing. CONCLUSION: In
      neutropenic cancer patients with persistent fever the combination of antibiotics
      with AmB/5-FC is superior to salvage antibacterial therapy alone. There is no
      difference in efficacy between Pip and third generation Ceph given as initial
      empirical therapy in combination with an AMG.

PMID- 16804655
TI  - Piperacillin/tazobactam vs imipenem/cilastatin in the treatment of nosocomial
      pneumonia--a double blind prospective multicentre study.
AB  - BACKGROUND: Piperacillin/tazobactam (P/T) with its broad spectrum of
      antibacterial activity is used widely for the treatment of moderate to severe
      polymicrobial nosocomial infections. PATIENTS AND METHODS: The efficacy and
      safety of P/T was compared with imipenem/cilastatin (I/C) in patients with
      established nosocomial pneumonia. This multicentre study took place from January
      1999 to December 2001. Due to difficulties in recruiting sufficient patients it
      was terminated prematurely. In all, 221 patients were randomly assigned to either
      P/T at 4 g/0.5 g (n = 110) or I/C at 1 g/1 g (n = 111). Additional aminoglycoside
      therapy was mandatory if Pseudomonas aeruginosa was present. The ITT population
      (107 P/T and 110 I/C patients) was used for the analysis of efficacy. RESULTS:
      The clinical efficacy was equally good for the P/T and I/C groups; 71% [95% CI
      61.3, 79.2] vs 77.3% [95% CI 68.1, 84.5] at the end of therapy, 66.4% [95% CI
      56.5, 75] vs 70% [95% CI 60.4, 78.2] on day 3, a nd 59.8% [95% CI 49.9, 69] vs
      66.4% [95% CI 56.6, 74.9] on day 14 after therapy, respectively. Proven or
      assumed bacterial eradication at the end of therapy was 45.8% (P/T) and 52.7%
      (I/C). Treatment-related adverse events (AE) were recorded in 30% of P/T patients
      and 25.2% I/C patients. There were ten serious treatment-related AEs in the P/T
      group and five in the I/C group. CONCLUSION: Although numbers were inadequate for
      full statistical evaluation, P/T and I/C were similarly effective in the
      treatment of severe nosocomially acquired pneumonia.

PMID- 16804656
TI  - Influenza vaccination coverages among Spanish children, adults and health care
      workers.
AB  - BACKGROUND: This study aimed at describing influenza vaccination coverage among
      Spanish children, adults and health care workers (HCWs). PATIENTS AND METHODS: We
      analyzed 27,791 questionnaires on subjects aged 6 months or over, drawn from the
      2003 Spanish National Health Survey. As the dependent variable, we took the
      answer to the question, "Did you (or your child) have a flu shot in the last
      campaign?". Independent variables were age group, gender, nationality, occupation
      (HCWs) and coexistence of chronic conditions. RESULTS: Overall influenza
      vaccination coverage for the total sample was 19.58%. Coverage for the pediatric
      population was 5.55%, with 20.74% of those with and 4.67% of those without
      chronic condition being vaccinated. Vaccination coverages were: 63.7% among
      subjects aged > or = 65 years; 30.5% among high-risk subjects aged < 65 years;
      and 19.65% among HCWs. CONCLUSIONS: We conclude that the available results show
      low levels of influenza vaccination coverage among high-risk subjects aged under
      65 years, children in particular, and HCWs.

PMID- 16804657
TI  - Influenza vaccination of healthcare workers: a literature review of attitudes and
      beliefs.
AB  - BACKGROUND: Influenza vaccination coverage among healthcare workers (HCW) is
      insufficient despite health authority recommendations in many countries. Numerous
      vaccination campaigns encouraging HCW to be vaccinated have met with resistance.
      We reviewed published influenza vaccination programs in healthcare settings to
      understand the reasons for their success and failure, as well as the attitudes
      and beliefs of HCW. METHODS: Relevant articles published up to June 2004 were
      identified in the MEDLINE/Pubmed database. RESULTS: Thirty-two studies performed
      between 1985 and 2002 reported vaccination rates of 2.1-82%. Vaccination
      campaigns including easy access to free vaccine and an educational program tended
      to obtain the highest uptake, particularly in the USA. Yet, even this type of
      campaign was not always successful. Two main barriers to satisfactory vaccine
      uptake were consistently reported: (1) misperception of influenza, its risks, the
      role of HCW in its transmission to patients, and the importance and risks of
      vaccination (2) lack of (or perceived lack of) conveniently available vaccine.
      CONCLUSION: To overcome these barriers and increase uptake, vaccination campaigns
      must be carefully designed and implemented taking account of the specific needs
      at each healthcare institution.

PMID- 16804658
TI  - A holistic approach to MRSA eradication in critically ill patients with MRSA
      pneumonia.
AB  - BACKGROUND: The number of Methicillin-resistant Staphylococcus aureus (MRSA)
      pneumonia cases is increasing in many European countries. In this observational
      study in one medical and three surgical ICUs multiple interventions for the
      treatment and eradication of nosocomial MRSA-pneumonia were used. PATIENTS AND
      METHODS: Twenty-one critically ill patients (age: 59 +/- 14 years, 15 males/6
      females, 18 ventilator-associated, 3 nosocomial, clinical pulmonary infection
      score > 6 in all patients, APACHE II 18 +/- 5) were enrolled. The patients were
      treated with a 7-day course of iv linezolid (600 mg bid) plus rifampicin (600 mg
      bid), endotracheal vancomycin 100 mg qid, thrice daily mouth and throat washing
      with chlorhexidine 1% fluid and nasal mupirocin ointment, twice daily skin and
      hair washings with chlorhexidine gluconate 4% and tracheostomy (n = 8) wound care
      with povidone-iodine spray. Control samples (endotracheal secretions, nose,
      wound, and pharyngeal swabs) were taken 2, 3, 4, 7 days and 2 months thereafter.
      Multilobular pneumonia was seen in 16, pleural effusion in 12, and MRSA
      bacteremia in 4 patients. RESULTS: One patient died during the follow-up period
      due to cerebral bleeding. In the remaining 20 patients, pneumonia was clinically
      cured in all patients and all patients were free of MRSA after eradication. Six
      patients died due to myocardial infarction (n = 3), gram-negative septic shock (n
      = 2), herpes encephalitis (n = 1) > 7 days after eradication. No MRSA reinfection
      occurred during the control period. CONCLUSION: We conclude that in patients with
      MRSA pneumonia an approach using a 7-day course of intravenous linezolid plus
      rifampicin, intratracheal vancomycin, nasal mupirocin, cutaneous and
      oropharyngeal chlorhexidin plus povidone-iodine cures pneumonia and is effective
      for MRSA eradication.

PMID- 16804659
TI  - Antibiotic treatments for children ages 0-23 months in a northern Italy region: a
      cohort study.
AB  - BACKGROUND: This study aims to describe the pattern of antibiotic treatments in
      the community for children ages 0-23 months in Emilia-Romagna (a northern Italy
      region) pointing out possible changes of prescribed agents when first treatments
      in the life of each children are compared to successive ones. MATERIALS AND
      METHODS: The Regional Drug Prescription and the Resident Population databases
      were used as data sources to study the cohort of children born between January 1
      and December 31, 2000 and resident in Emilia-Romagna. RESULTS: The cumulative
      incidences of children with at least one treatment were 22%, 55% and 82% at 6, 12
      and 24 months of age, respectively. Broad spectrum penicillins were the most
      prescribed antibiotic class for children at their first treatment while
      cephalosporins were the most prescribed class for successive treatments and when
      pooling all treatments. CONCLUSION: Cephalosporins and other second line
      antibiotics are frequently prescribed to 0 to 23-month-old residents in Emilia
      Romagna even when only first treatments are considered; further research is
      needed to quantify inappropriateness of antibiotic prescription.

PMID- 16804660
TI  - Serum levels of interleukin-18 (IL-18), interleukin-1beta (IL-1beta), its soluble
      receptor sIL-1RII and C-reactive protein (CRP) in patients with Lyme arthritis.
AB  - BACKGROUND: In recent years, the role of pro- and antiinflammatory cytokines in
      the development of Lyme arthritis (LA) has been widely discussed. The purpose of
      the present study was to determine the concentration of interleukin-18 (IL-18),
      interleukin-1beta (IL-beta) and its soluble receptor sIL-1RII in serum of
      patients with LA as well as the usefulness of serum C-reactive protein (CRP)
      determination in LA diagnosis and monitoring of its treatment. PATIENTS AND
      METHODS: The study group consisted of 20 patients with LA. Before and after
      antibiotic treatment, the serum levels of IL-18, IL-1beta and sIL-1RII were
      measured immunoenzymatically using standard kits and the CRP level was measured
      by immunoturbidimetric method. RESULTS: Before treatment, the serum levels of IL
      18, IL-1beta and sIL-1RII were significantly higher than in control group and
      after treatment the concentrations of IL-18, IL-1beta and sIL-1RII decreased
      significantly, but the level of IL-18 and sIL-1RII still remained higher than in
      control group. The elevated serum level of CRP was detected only in 6 of 20
      patients and in 5 of them it returned to the baseline after treatment.
      CONCLUSION: The results of our study suggest that IL-18, IL-1beta and sIL-1RII
      might be involved in the development of LA. CRP may be useful in differential
      diagnosis in patients with suspicion of Lyme arthritis.

PMID- 16804661
TI  - Hearing loss after discontinuing secondary prophylaxis for cryptococcal
      meningitis: relapse or immune reconstitution?
AB  - Relapse and immune reconstitution syndrome are difficult to distinguish in HIV
      infected patients treated with antiretroviral therapy (ART). We report on a 26
      year-old HIV-infected male (CDC C3) with hearing loss on the right side 2 months
      after discontinuing secondary prophylaxis for cryptococcal meningitis. CD4 cell
      counts had increased from 32/microl to stable counts > 200/microl for the
      preceding 6 months on ART but HIV replication was not fully suppressed (7,000
      copies/ml). Magnetic resonance imaging identified lesions at the origin of the
      right cranial nerve VIII. Lumbar puncture revealed monocytic pleocytosis,
      slightly increased protein, but normal glucose and lactate levels, negative
      microbiological studies. Fluconazole was restarted and a new ART regimen was
      started in order to fully suppress HIV replication. Clinical and radiological
      signs were reversible during follow-up, and secondary prophylaxis was stopped
      after 6 months without adverse events. We review 26 published cases of
      cryptococcal infections with immune reconstitution syndrome and highlight the
      distinguishing features.

PMID- 16804662
TI  - Simultaneous ocular and systemic cysticercosis and tuberculosis.
AB  - Human cysticercosis and tuberculosis are endemic diseases in developing
      countries. Both these diseases have certain common factors of origin. We would
      like to present the co-existence of these infections in a 20-year-old female. She
      was a known case of pulmonary and ocular tuberculosis and she acquired
      cysticercosis of the eye and brain.

PMID- 16804663
TI  - Autochthonous hepatitis E virus infection in Germany with sequence similarities
      to other European isolates.
AB  - Hepatitis E virus (HEV) is a common cause of acute hepatitis in endemic areas.
      Yet reports on autochthonous cases in other areas such as middle Europe are
      increasing. Here we report on a patient, who obviously acquired his HEV infection
      in Germany. Sequence analysis of the virus gained from his serum revealed
      homologies to other European isolates and swine isolates.

PMID- 16804664
TI  - Human papillomavirus associated with papillary squamous cell carcinoma of the
      oropharynx in a renal transplant recipient.
AB  - The papillary squamous cell carcinoma (PSCC) is a rare variant of the head and
      neck squamous cell carcinoma. Established etiological factors can include tobacco
      smoking and heavy alcohol abuse. Moreover, human papillomavirus infection can be
      involved in the pathogenesis of PSCC. This tumor is more frequent in patients
      with immunosuppression including those who have received a transplant. Most of
      the cases are produced by genotype HPV-6 and HPV-16, although there is a
      possibility of infection by other HPV subtypes. We present a case report of a
      PSCC and papilloma with oropharyngeal location in which high-risk HPV type 16 and
      low-risk HPV type 6, respectively, were identified by PCR in a renal transplant
      patient.

PMID- 16804665
TI  - Intracranial tuberculomas in an immunocompetent patient mimicking brain
      metastasis of unknown origin.

PMID- 16804666
TI  - Blood transaminase elevation with pegylated interferon alfa 2b plus ribavirin in
      an HIV/HCV coinfected haemophilic patient.

PMID- 16804667
TI  - Treatment interruption in HIV therapy: a SMART strategy?
AB  - Continuous HAART is standard of care for HIV-infected patients but lifelong
      adherence and tolerance are important concerns. Use of ART is associated with
      potential risks, e. g., adverse events, metabolic and cardiovascular
      complications, and HIV resistance. Stopping HIV therapy may reduce costs and side
      effects, but carries the risk of increased immune suppression and of emergence of
      resistance. Treatment interruption is a strategy of much interest, but its safety
      and efficacy have not been established. The clinical and biological
      characteristics that influence the outcome of structured treatment interruptions
      have not been fully clarified. In the following we will present the results of
      recent studies aimed to compare the long-term consequences of two antiretroviral
      management strategies: continuous therapy versus scheduled treatment
      interruption.

PMID- 16804668
TI  - Depressed type of inflammatory fibroid polyp of the colon.

PMID- 16804669
TI  - Implantation of adenocarcinoma on hemorrhoidectomy wound.

PMID- 16804670
TI  - NOD2/CARD15 gene polymorphisms are not associated with collagenous colitis.
AB  - BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease of
      unknown origin. In some cases of collagenous colitis, histomorphological features
      are comparable to other inflammatory bowel diseases. AIM: To assess functional
      NOD2/CARD15 polymorphisms for the susceptibility to collagenous colitis in a case
      control study. MATERIALS AND METHODS: Seventy-five patients with symptomatic
      collagenous colitis and 534 healthy blood donors were genotyped for SNP 8, 12,
      and 13 of the NOD2/CARD15 gene using TaqMan technology. Susceptibility to
      collagenous colitis was tested using Chi(2)-test comparing the carrier status of
      the rare allele. RESULTS: The carrier frequency of the rare allele in SNP 8, 12,
      and 13 was 9.5, 1.3, and 8.1% in patients with collagenous colitis and 8.9, 1.1,
      and 8.4% in healthy blood donors, respectively. There were no significant
      differences in allele-, genotype, and carrier frequency (p>0.05). CONCLUSION: Our
      data suggest that functional polymorphisms in the NOD2/CARD15 gene might not be
      involved in the susceptibility to collagenous colitis.

PMID- 16804672
TI  - Characterisation of two novel cyclodextrinases using on-line microdialysis
      sampling with high-performance anion exchange chromatography.
AB  - In this work, a real-time sampling/analytical method for on-line measurements of
      two newly discovered cyclomaltodextrinases (CDases) has been developed and
      evaluated. This novel methodology not only allows the final products to be
      investigated, but it also reveals enzyme-specific differences in the degradation
      pathways during the hydrolysis of different substrates, which is a great
      advantage in the important tasks of investigating the mechanisms of and
      classifying new hydrolases, and is an advantage that conventional techniques
      cannot offer. Two different enzymes, one CDase from Laceyella sacchari (LsCda13)
      and one from Anoxybacillus flavithermus (AfCda13), were investigated during the
      hydrolysis of alpha-, beta- and gamma-cyclodextrin, and the hydrolysis products
      were sampled via a microdialysis probe and injected on-line every 30 min into a
      high-performance anion exchange chromatography system equipped with a pulsed
      amperometric detector (HPAEC-PAD), where they were identified. The enzymes
      yielded the same end-products, maltose and glucose, in an approximate molar ratio
      of 2:1, but they exhibited distinctly different patterns of intermediate product
      formation before reaching the end-point. LsCda13 had a more random distribution
      of the intermediate products, whereas AfCda13 showed the distinct intermediate
      production of maltotriose, which in some cases accumulated.

PMID- 16804671
TI  - The impact of diabetes mellitus on cognitive decline in the oldest of the old: a
      prospective population-based study.
AB  - AIMS/HYPOTHESIS: Diabetes mellitus is a risk factor for the development of
      cognitive impairment and dementia in the general population up to 75 years of
      age. As part of the Leiden 85-plus Study we studied the effects of diabetes on
      cognition in the oldest old. SUBJECTS AND METHODS: The Leiden 85-plus Study is a
      prospective population-based study of 599 persons from age 85 onward. Cognitive
      function was assessed each year from ages 85 to 90 by means of four
      neuropsychological tests. The presence of diabetes and vascular disease was
      recorded at baseline, HbA(1c) was assessed by means of a blood sample at ages 85
      and 90. The cross-sectional and prospective associations between diabetes and
      cognitive function were analysed with linear mixed models, adjusted for sex and
      level of education. RESULTS: At age 85, diabetes was associated with a lower
      level of cognitive functioning on the Letter Digit Coding test and the Stroop
      Test. Diabetes was not associated with accelerated cognitive decline during
      follow-up. Within the group of diabetic patients, macrovascular disease was the
      most important determinant of cognitive dysfunction. CONCLUSIONS/INTERPRETATION:
      The association between diabetes and accelerated cognitive decline, which has
      been documented previously in patients up to 75 years of age, may be less evident
      after age 85. This suggests that the damage occurs in previous years and that
      therapies aimed at preventing cognitive decline and dementia should focus on the
      younger old.

PMID- 16804673
TI  - Cholinesterase inhibition based determination of pancuronium bromide in
      biological samples.
AB  - Pancuronium bromide (PCBr) inhibition effect on enzyme cholinesterase from pooled
      human serum (Che, EC 3.1.1.8 acylcholine acylhydrolase) was used for development
      of a spectrophotometric kinetic method for PCBr determination in human serum and
      urine. Optimal conditions for the basic and inhibitor reactions were established:
      pH=7.7 and substrate concentration c(benzoylcholine chloride)=1.33 mmol/L.
      Kinetic parameters were also determined: Michaelis-Menten's constant K(M)=0.40
      mmol/L, maximal reaction rate V(max)=52.2 micromol/L min, inhibition constant
      K(i)=0,56 micromol/L and IC(50)=1.31 micromol/L. Linear dependence between the
      reaction rate and inhibitor concentration exists in PCBr concentration range 8.20
      68.25 nmol/L, which corresponds to the real sample concentrations from 0.328 to
      2.730 micromol/L. The method detection and quantification limits were 2.01 nmol/L
      and 6.67 nmol/L, respectively. Precision of the method was tested for three
      pancuronium concentrations (10.70, 29.35 and 51.25 nmol/L). Relative standard
      deviation (RSD) was in the range 0.15-7.45%. Accuracy was examined by standard
      addition method. Influence of the substances usually present in serum and urine
      on the reaction rate was tested. The developed method was applied for PCBr
      content determination in serum model samples, urine model samples and in urine
      taken during surgery. The method has good sensitivity, accuracy, precision and it
      is suitable for clinical practice.

PMID- 16804674
TI  - Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia
      more rapidly than spinal cord-evoked potentials monitoring during aortic
      occlusion in rats.
AB  - In this study, we evaluated the efficacy of transcranial motor-evoked potentials
      (tc-MEPs), compared with segmental spinal cord-evoked potentials (SCEPs), for
      detecting spinal cord ischemia (SCI) and assessed the relationship between
      neurological outcome and tc-MEPs or SCEPs in the rat aortic occlusion model. In
      the rats, SCI was induced by aortic occlusion for 10 min with a balloon catheter.
      At first, tc-MEPs (Group A: n = 6) or segmental SCEPs (Group B: n = 6) was
      recorded during SCI. Second, in using the quantal bioassay for the relationship
      between an interval of aortic occlusion and the probability of positive response
      in tc-MEPs or segmental SCEPs, the P50(MEP) and P50(SCEP) which represent the
      interval of aortic occlusion associated with 50% probability of assessment of
      ischemic spinal cord dysfunction by tc-MEP and SCEP were analyzed. The amplitude
      of tc-MEPs decreased significantly at 30 s and disappeared completely at 2 min
      after aortic occlusion. In Group B, it took about 6 min after aortic occlusion to
      diminish SCEP signal amplitude by approximately 50%. P50(MEP) obtained in the
      quantal analysis was 0.3 +/- 0.1 min. P50(SCEP) was calculated as 6.2 +/- 0.5 min
      that was significantly (P < 0.01) longer than P50(MEP). Our data indicated that
      tc-MEP monitoring could detect the onset of SCI so rapidly in comparison with
      segmental SCEP monitoring, which could provide therapeutic windows in a surgical
      approach that includes spinal cord protection.

PMID- 16804675
TI  - Intraoperative pulmonary embolism of Harrington rod during spinal surgery: the
      potential dangers of rod cutting.
AB  - This is a case report and laboratory-based biomechanics study. The objective is
      to report the first case of Titanium rod embolisation during scoliosis surgery
      into the Pulmonary artery. To investigate the potential of an unconstrained cut
      Titanium rod fragment to cause wounding with reference to recognised weapons.
      Embolisation of a foreign body to the heart is rare. Bullet embolisation to the
      heart and lungs is infrequently reported in the last 80 years. Iatrogenic cases
      of foreign body embolisation are very rare. Fifty 1-2 cm segments of Titanium rod
      were cut in an unconstrained manner and a novel method was used to calculate
      velocity. A high-speed camera (6,000 frames/s) was used to further measure
      velocity and study projectile motion. The wounding potential was investigated
      using lambs liver, high-speed photography and local dissection. Rod velocities
      were measured in excess of 23 m s(-1). Rods were seen to tumble end-over-end with
      a maximum speed of 560 revolutions/s. The maximum kinetic energy was 0.61 J which
      is approximately 2% that of a crossbow. This is sufficient to cause significant
      liver damage. The degree of surface damage and internal disruption was influenced
      by the orientation of the rod fragment at impact. An unconstrained cut segment of
      a Titanium rod has a significant potential to wound. Precautions should be taken
      to avoid this potentially disastrous but preventable complication.

PMID- 16804676
TI  - Selectivity at a three-base bulge site in the DNA binding of DeltaDelta
      [{Ru(phen)2} 2(mu-dppm)]4+ [dppm is 4,6-bis(2-pyridyl)pyrimidine; phen is 1,10
      phenanthroline].
AB  - The binding of the stereoisomers of [{Ru(phen)2}2(mu-bpm)]4+, [{Ru(phen)2}2(mu
      dppm)]4+ and [{Ru(phen)2}2(mu-bb)]4+ {phen is 1,10-phenanthroline; bpm is 2,2'
      bipyrimidine, dppm is 4,6-bis(2-pyridyl)pyrimidine, bb is 1,2-bis[4-(4'-methyl
      2,2'-bipyridyl)]ethane} to an oligonucleotide duplex
      [d(GCATCGAAAGCTACG).d(CGTAGCCGATGC)] containing a three-base bulge has been
      studied using a fluorescence intercalator displacement assay. Of the dinuclear
      ruthenium complexes, the dppm-linked species showed the strongest binding to the
      oligonucleotide, with the DeltaDelta isomer binding slightly more strongly than
      the meso isomer and the LambdaLambda isomer exhibiting the weakest binding. In
      order to determine whether the DeltaDelta-[{Ru(phen)2}2(mu-dppm)]4+ metal complex
      specifically bound at the three-base bulge site, a 1H NMR study of the binding of
      the metal complex to the oligonucleotide duplex
      d(GCATCGAAAGCTACG)*d(CGTAGCCGATGC) was carried out. Although a detailed picture
      of the metal complex-oligonucleotide association could not be determined from the
      NMR results owing to the broadening of the resonances from the metal complex and
      nucleotide residues at the bulge site, the NMR results do indicate that the metal
      complex specifically binds at the three-base bulge site. The combined results of
      this study suggest that the dppm-bridged dinuclear ruthenium complexes have
      considerable potential as probes for the unusual secondary structure obtained by
      the insertion of a three-base bulge within duplex DNA.

PMID- 16804677
TI  - Divalent-metal-dependent nucleolytic activity of Cu, Zn superoxide dismutase.
AB  - The known action of Cu, Zn superoxide dismutase (holo SOD) that converts O2- to
      O2 and H2O2 plays a crucial role in protecting cells from toxicity of oxidative
      stress. However, the overproduction of holo SOD does not result in increased
      protection but rather creates a variety of unfavorable effects, suggesting that
      too much holo SOD may be injurious to the cells. In the in vitro study, we report
      a finding that the holo SOD from bovine erythrocytes and its apo form possess a
      divalent-metal-dependent nucleolytic activity, which was confirmed by UV-vis
      absorption titration of calf thymus DNA (ctDNA) with the holo SOD, quenching of
      holo SOD intrinsic fluorescence by ctDNA, and by gel electrophoresis monitoring
      conversion of DNA from the supercoiled DNA to nicked and linear forms, and
      fragmentation of a linear lambdaDNA. Moreover, the DNA cleavage activity was
      examined in detail under certain reaction conditions. The steady-state study
      indicates that DNA cleavage supported by both forms of SOD obeys Michaelis-Menten
      kinetics. On the other hand, the assays with some other proteins indicate that
      this new function is specific to some proteins including the holo SOD. Therefore,
      this study reveals that the divalent-metal-dependent DNA cleavage activity is an
      intrinsic property of the holo SOD, which is independent of its natural metal
      (copper and zinc) sites, and may provide an alternative insight into the link
      between SOD enzymes and neurodegenerative disorders.

PMID- 16804678
TI  - Structural studies of constitutive nitric oxide synthases with diatomic ligands
      bound.
AB  - Crystal structures are reported for the endothelial nitric oxide synthase (eNOS)
      arginine-CO ternary complex as well as the neuronal nitric oxide synthase (nNOS)
      heme domain complexed with L: -arginine and diatomic ligands, CO or NO, in the
      presence of the native cofactor, tetrahydrobiopterin, or its oxidized analogs,
      dihydrobiopterin and 4-aminobiopterin. The nature of the biopterin has no
      influence on the diatomic ligand binding. The binding geometries of diatomic
      ligands to nitric oxide synthase (NOS) follow the {MXY}(n) formalism developed
      from the inorganic diatomic-metal complexes. The structures reveal some subtle
      structural differences between eNOS and nNOS when CO is bound to the heme which
      correlate well with the differences in CO stretching frequencies observed by
      resonance Raman techniques. The detailed hydrogen-bonding geometries depicted in
      the active site of nNOS structures indicate that it is the ordered active-site
      water molecule rather than the substrate itself that would most likely serve as a
      direct proton donor to the diatomic ligands (CO, NO, as well as O(2)) bound to
      the heme. This has important implications for the oxygen activation mechanism
      critical to NOS catalysis.

PMID- 16804679
TI  - Characterization of the Vibrio cholerae vexAB and vexCD efflux systems.
AB  - Vibrio cholerae is an important human pathogen that causes the diarrheal disease
      cholera. Colonization of the human host is dependent upon coordinated expression
      of several virulence factors in response to as yet unknown environmental cues.
      Bile acids have been implicated in the in vitro regulation of several V. cholerae
      genes, including those involved in motility, chemotaxis, outer membrane protein
      production, and virulence factor production. Bile is toxic to bacteria and
      colonization of the intestinal tract is dependent upon bacterial resistance to
      bile acids. We have identified and characterized two bile-regulated RND-family
      efflux systems, named here vexAB and vexCD, that are involved in V. cholerae bile
      resistance. Mutational analysis revealed that the vexAB system is responsible for
      in vitro intrinsic resistance of V. cholerae to multiple antimicrobial compounds,
      including bile acids. In contrast, the vexCD efflux system was specific for
      certain bile acids and detergents and functioned in conjunction with the vexAB
      system to provide V. cholerae with high-level bile resistance. Mutants containing
      deletion of vexB, vexD, and vexB-vexD were able to efficiently colonize the
      infant mouse suggesting that these efflux systems were dispensable for V.
      cholerae growth in the small intestines of infant mice.

PMID- 16804680
TI  - Plasmids for expression of heterologous proteins in Rhizopus oryzae.
AB  - Rhizopus oryzae has long been used for enzyme production (e.g., glucoamylase and
      lipase), organic acid synthesis, and various fermented food applications. In this
      work, we describe a set of plasmid-based expression vectors that can be used for
      the production of heterologous proteins in R. oryzae. Three plasmid vectors have
      been created using either the glucoamylase A (amyA), pyruvate decarboxylase
      (pdcA), or phosphoglycerate kinase (pgk1) promoters to drive expression of
      heterologous proteins. All three plasmids use the pdcA terminator for
      transcription termination, the pyrG gene for restoration of uracil prototrophy,
      and an ampicillin resistance gene and origin of replication for maintenance in
      Escherichia coli. We have expressed green fluorescent protein (GFP) and compared
      transcription and protein accumulation for each of the expression vectors.
      Accumulation of GFP transcript and protein was directly correlated with the
      choice of promoter with pdcA > amyA > pgk1. Transcript level appears to parallel
      GFP protein accumulation. Plasmid copy number had little impact on transcription
      or protein accumulation. These vectors should be useful for overexpression of
      heterologous proteins and potentially, metabolic engineering of Rhizopus strains.

PMID- 16804681
TI  - Expression and processing of Vibrio anguillarum zinc-metalloprotease in
      Escherichia coli.
AB  - The extracellular zinc-metalloprotease of Vibrio anguillarum is a secreted
      virulence factor. It is synthesized from the empA gene as a 611-residue
      preproprotease and processed to the active mature protease (EmpA) with
      concomitant secretion via the type II secretion pathway. Active EmpA has been
      found only in the V. anguillarum culture supernatant and the process of the
      activation seems to vary depending on strains analyzed. To better understand the
      mechanism of EmpA export and processing, the empA gene was cloned and expressed
      in Escherichia coli strains. Expression of empA did not have toxic effect on
      bacterial growth. Rupturing E. coli TOP10 cells by heating in gel-loading buffer
      resulted in activation of EmpA and severe proteolysis of the samples. In
      contrast, the same treatment of the E. coli MC4100A strain did not lead to the
      general proteolysis. In this strain, EmpA was exported into the periplasm via the
      Sec pathway. The periplasmic EmpA was detected in two active conformations.
      Therefore, in E. coli processing of EmpA precursor to an active enzyme did not
      require secretion to the media and the help of other V. anguillarum protein. Like
      in V. anguillarum, heterologous expression of empA in E. coli showed strain
      specific activation process.

PMID- 16804682
TI  - Microbial studies of a selenium-contaminated mine site and potential for on-site
      remediation.
AB  - Surface water Selenium (Se) concentrations are above regulatory standards at
      several active and inactive phosphate mine sites in the US Western Phosphate
      Resource Area. The focus of the present study was to examine the impacts of the
      microbial communities on the oxidation state of Se in overburden waste from the
      Smoky Canyon phosphate mine in Idaho, USA. Microbial populations were found that
      reduce soluble selenate (SeO (4) (2-) ) to insoluble elemental Se. Microcosm
      experiments were conducted for molecular genetic analysis of this microbial
      community by rRNA gene profiling. An acetone pretreatment step was developed to
      remove interfering pre-petroleum hydrocarbons from the samples prior to
      extraction. PCR was used to amplify 16S and 18S rRNA genes present in the
      microbial community DNA. The amplified products were subjected to denaturing
      gradient gel electrophoresis (DGGE). Isolates and excised DGGE bands were
      amplified and sequenced for identification to determine the relative importance
      of culturable isolates to the total microbial population. Analysis of samples
      from different sites at the mine showed how Se contamination and previous
      remediation treatments changed the microbial populations across the site. Members
      of the family Enterobacteriaceae were dominant among the selenate reducing
      isolates from the site containing high Se levels. In particular, Serratia
      fonticola was isolated repeatedly from contaminated Smoky Canyon Mine site
      samples. Packed column studies were performed with seleniferous waste rock
      fractions from Smoky Canyon Mine. Column amendments consisted of combinations of
      iron, compost, and whey. Eh, pH, and extractable Se measurements were taken.
      Tests with infiltrated water showed columns containing an organic amendment
      combined with iron metal were the most resistant to Se leaching. Iron-based
      compounds from the corroding metal are thought to strongly bind the Se reduced by
      microbial activity, thereby stabilizing the Se in an insoluble form. We conclude
      that long-term stabilization of selenium at contaminated mine sites may require
      reductive microbial processes combined with abiotic immobilization by iron,
      either natural or engineered, to stabilize the Se and retard re-oxidation and
      release. Iron-selenide or iron-selenite compounds are more stable and resistant
      to leaching, especially when removed from active weathering.

PMID- 16804684
TI  - [Airway management in pediatric anesthesia].
AB  - Airway management in newborns, infants, and children is a challenge to anesthesia
      practitioners due to the particular anatomic and physiological characteristics.
      The larynx is positioned more cephalad, the occiput is protuberant, and the neck
      is short, which makes a special position for anesthesia induction necessary. The
      high respiratory frequency due to high oxygen demand and carbon dioxide
      production has to be taken into consideration during manual as well as mechanical
      ventilation. Different devices are available for airway management. Simple mask
      ventilation can be improved by a Wendl tube. The classic laryngeal mask can be
      recommended as a safe airway device in many indications, specifically in children
      with an upper respiratory airway infection. If intubation is indicated, an
      optimal size and position of the endotracheal tube has to be provided. Fiberoptic
      endotracheal intubation is recommended if a difficult airway is known or
      anticipated due to a craniofacial syndrome.

PMID- 16804683
TI  - [Anesthetic management of surgery in term and preterm infants].
AB  - The physiology of the preterm and term neonate is characterized by a high
      metabolic rate, limited pulmonary, cardiac and thermoregulatory reserve and
      decreased renal function. Multisystem immaturity creates important developmental
      differences in drug administration and response when compared to older children.
      Specific monitoring techniques are required because the neonate is not physically
      accessible to the anesthetist during the operation. This contribution reviews the
      specific pathophysiological characteristics of the newborn with relevance to
      anesthesia and also provides robust guidelines for the anesthetic management of
      the most frequent non-cardiac procedures which need surgery during the neonatal
      period. Consideration will also be given to the anesthetic management of very low
      birth-weight infants with anesthetic key issues such as avoiding hyperoxia,
      keeping hemodynamic parameters as stable as possible and preventing hypothermia.

PMID- 16804685
TI  - [Preoperative autologous blood donation in cardiac surgery. Reduction of
      allogeneic blood requirements].
AB  - BACKGROUND: Preoperative autologous blood donation is an effective method to
      reduce allogeneic transfusion requirement. However, this method is only rarely
      utilized in cardiac surgery. Besides economic concerns one essential argument
      against predonation is the lack of sufficient time due to the short waiting
      lists. The aim of the present study was to investigate the efficacy of autologous
      predonation to reduce allogeneic blood transfusion in routine cardiac surgery on
      a center without longer preoperative waiting lists. PATIENTS AND METHODS: A total
      of 2,626 cardiac surgery patients were included. Primary endpoint of the study
      was the perioperative incidence of allogeneic packed cell transfusion. If time
      between diagnosis and admission to the hospital was >10 days, predonation was
      offered to the patients. Data were stratified for preoperative risk score.
      Logistic and linear regression analysis tested the influence of different
      variables on the incidence of allogeneic blood transfusion and the total amount
      of allogeneic blood. RESULTS: Of all patients 267 (11.2%) underwent predonation.
      The incidence of allogeneic packed cell transfusion was reduced from 53% to 19%
      by autologous predonation (p<0.001). The total amount of allogeneic blood
      transfused was significantly different between the groups (2.2+/-4.2 vs. 0.84+/
      6.3 units; p<0.001). DISCUSSION: Autologous predonation in cardiac surgery was
      effective in reducing blood transfusions even in the absence of longer
      preoperative waiting times. It is a safe and effective method to minimize blood
      transfusion in cardiac surgery.

PMID- 16804686
TI  - (99m)Tc-NC100668, a new tracer for imaging venous thromboemboli: pre-clinical
      biodistribution and incorporation into plasma clots in vivo and in vitro.
AB  - PURPOSE: (99m)Tc-NC100668 is a new radiotracer being developed to aid the
      diagnosis of thromboembolism. The structure of NC100668 is similar to a region of
      human alpha(2)-antiplasmin, which is a substrate for factor XIIIa (FXIIIa). The
      purpose of this study was to confirm the uptake of (99m)Tc-NC100668 into forming
      plasma clot and to establish the biodistribution of (99m)Tc-NC100668 in Wistar
      rats. METHODS: The in vitro plasma clot uptake of (99m)Tc-NC100668 and other
      compounds with known affinities to FXIIIa was measured using a plasma clot assay.
      The biodistribution and blood clot uptake of radioactivity of (99m)Tc-NC100668 in
      normal Wistar rats and those bearing experimentally induced deep vein thrombi
      were investigated. RESULTS: The in vitro uptake of (99m)Tc-NC100668 was greater
      than that for [(14)C]dansyl cadaverine, a known substrate of FXIIIa in the plasma
      clot assay. The biodistribution of (99m)Tc-NC100668 in male and female Wistar
      rats up to 24 h p.i. showed that radioactivity was rapidly excreted,
      predominantly into the urine, with very little background tissue retention. In
      vivo the uptake and retention of (99m)Tc-NC100668 into the blood clot was greater
      than could be accounted for by non-specific accumulation of the radiotracer
      within the blood clot. CONCLUSION: (99m)Tc-NC100668 was retained by plasma clots
      in vitro and blood clots in vivo. No significant tissue retention which could
      interfere with the ability to image thrombi in vivo was observed. This evidence
      suggests that (99m)Tc-NC100668 might be useful in the detection of
      thromboembolism.

PMID- 16804687
TI  - Time-of-flight PET and PET/MRI: recurrent dreams or actual realities?

PMID- 16804688
TI  - Role of 99mTc-sestamibi SPECT in accurate selection of primary hyperparathyroid
      patients for minimally invasive radio-guided surgery.
AB  - PURPOSE: A prerequisite for optimum minimally invasive radio-guided surgery
      (MIRS) for primary hyperparathyroidism (PHPT) is the demonstration of significant
      uptake of (99m)Tc-sestamibi in a parathyroid adenoma (PA). The aim of this study
      was to evaluate the clinical role or (99m)Tc-sestamibi SPECT in selecting
      patients for this procedure. METHODS: Fifty-four consecutive PHPT patients were
      evaluated by single-session (99m)Tc-pertechnetate/(99m)Tc-sestamibi planar
      subtraction scintigraphy, followed by (99m)Tc-sestamibi SPECT acquisition to
      localise hyperfunctioning PAs and assist in planning the surgical approach.
      RESULTS: Scintigraphy showed the presence of a solitary PA in 47/54 patients
      (87%) and two or more PAs in four patients (7.4%); it was negative in the
      remaining three patients (5.6%). The overall sensitivity of (99m)Tc-sestamibi
      scintigraphy was 94.6%. In 7/54 patients, the PA was located deep in the para
      oesophageal/paratracheal space. So far, 22 patients with scintigraphic evidence
      of a solitary PA (in four of whom the PA was located deep in the neck) have
      undergone successful MIRS using the low 37 MBq (1 mCi) (99m)Tc-sestamibi dose
      protocol. Intraoperative quick parathyroid hormone (QPTH) assay demonstrated a
      fall in all 22 patients, thus confirming successful removal of the
      hyperfunctioning PA. No major surgical complications were observed. After a
      period of follow-up ranging between 6 and 27 months (median 13 months), no case
      of persistent/recurrent PHPT was recorded. When comparing the parathyroid to
      background (P/B) ratio measured at planar and SPECT preoperative scintigraphy
      with that measured intraoperatively with the gamma probe, a good linear
      correlation was found between the SPECT and the intraoperative gamma probe
      measurements (r=0.89; p<0.01) but no correlation was found with planar
      scintigraphic data. CONCLUSION: Our preliminary data suggest that measurement of
      the P/B ratio by means of (99m)Tc-sestamibi SPECT is more accurate in predicting
      the intraoperative measurements with the gamma probe. In this respect, a
      preoperative (99m)Tc-sestamibi SPECT acquisition should be recommended for better
      selection of PHPT patients in whom a MIRS approach can be offered.

PMID- 16804689
TI  - The influence of wire localisation for non-palpable breast lesions on
      visualisation of the sentinel node.
AB  - PURPOSE: In our clinic, patients with occult breast lesions are treated with a
      sentinel node biopsy combined with wire-guided tumour excision. The aim of this
      retrospective study was to determine the influence of the sequence of wire
      localisation and sentinel node procedure on visualisation of the sentinel node.
      METHODS: A total of 136 patients had a wire-guided tumour excision combined with
      a sentinel node procedure. Sixty-six patients had guide wire localisation prior
      to the sentinel node procedure. Seventy patients had sentinel node visualisation
      before insertion of the guide wire. RESULTS: The sentinel node was visualised in
      41 (62%) of the patients who first underwent guide wire localisation. In the
      group of patients who underwent visualisation of the sentinel node before
      placement of the guide wire, the sentinel node was visualised in 62 (89%). This
      is a significant difference in visualisation (p<0.001). CONCLUSION: This study
      shows that guide wire localisation prior to the sentinel node procedure
      negatively influences visualisation of the sentinel node.

PMID- 16804690
TI  - Regional cerebral blood flow levels as measured by xenon-CT in vascular
      territorial low-density areas after subarachnoid hemorrhage are not always
      ischemic.
AB  - INTRODUCTION: The aim of this study was to assess regional cerebral blood flow
      (rCBV) in areas of CT hypoattenuation appearing in the postoperative period in
      patients treated for aneurysmal subarachnoid hemorrhage (SAH) using xenon
      enhanced CT scanning (Xe-CT). METHODS: We analyzed 15 patients (5 male and 10
      female; mean age 49.7+/-12.1 years) with SAH on CT performed on admission to
      hospital and who showed a low-density area within a well-defined vascular
      territory on CT scans after clipping or coiling of a saccular aneurysm. All zones
      of hypoattenuation were larger than 1 cm(2) and showed signs of a mass effect
      suggesting a subacute phase of evolution. Two aneurysms were detected in two
      patients. Aneurysms were located in the middle cerebral artery (n=7), in the
      anterior communicating artery (n=6), in the internal carotid artery (n=3), and in
      the posterior communicating artery (n=1). Treatments were surgical (n=8),
      endovascular (n=2) or both (n=1). A total of 36 Xe-CT studies were performed and
      rCBF values were measured in two different regions of interest (ROI): the low
      density area, and an area of normal-appearing brain tissue located symmetrically
      in the contralateral hemisphere. RESULTS: rCBF levels were significantly lower in
      the low-density area than in the contralateral normal-appearing area (P<0.01). In
      the low-density areas, irreversible ischemia (CBF <10 ml/100 g per minute) was
      present in 11/36 lesions (30.6%), ischemic penumbra (CBF 10-20 ml/100 g per
      minute) and oligemia (CBF 20-34 ml/100 g per minute) in 8/36 lesions (22.2%),
      relative hyperemia (CBF 34-55 ml/100 g per minute) in 7/36 lesions (19.4%), and
      absolute hyperemia (CBF >55 ml/100 g per minute) in 2/36 lesions (5.6%).
      CONCLUSION: Our study confirmed that rCBF is reduced in new low-density lesions
      related to specific vascular territories. However, only about one-third of the
      lesions showed rCBF levels consistent with irreversible ischemia and in a
      relatively high proportion of lesions, rCBF levels indicated penumbral, oligemic
      and hyperemic areas.

PMID- 16804691
TI  - Tobacco chippers show robust increases in smoking urge after alcohol consumption.
AB  - OBJECTIVE AND RATIONALE: Heavy social drinkers often engage in occasional
      cigarette smoking, especially in the context of consuming large quantities of
      alcohol. The current study assessed alcohol's effects on smoking urge as a
      function of alcohol dose and time course in tobacco chippers with heavy social
      drinking patterns. METHOD: The study assessed 39 chippers who underwent three
      separate evening sessions. Each subject received a placebo (1% volume alcohol as
      a taste mask), a low alcohol dose (two to three drinks equivalent), and a high
      alcohol dose (four to five drinks equivalent) in random order. No smoking was
      permitted during the sessions and the participants were abstinent from smoking
      for at least 3 h before arrival. Throughout the session, cigarette craving was
      assessed by the Brief Questionnaire of Smoking Urges and alcohol response was
      assessed by the Biphasic Alcohol Effects Scale (BAES). RESULTS: The results
      showed that alcohol significantly increased cigarette craving in a dose-dependent
      manner (p<0.001). At the high alcohol dose, craving was heightened during the
      rising portion of the blood alcohol curve (BAC). There was a strong relationship
      between BAC and craving for positive reinforcement and this relationship was
      partially mediated by BAES stimulation, but not sedation. CONCLUSIONS: The
      findings show that alcohol directly increases smoking urge in chipper smokers.
      Tobacco chippers may crave cigarettes more during heavier than during lighter
      drinking bouts, and this effect appears to be driven by heightened stimulation
      levels rather than as a means to offset alcohol's sedative effects.

PMID- 16804692
TI  - Enzymes and genes involved in the aerobic biodegradation of methyl tert-butyl
      ether (MTBE).
AB  - Fuel oxygenates, mainly methyl tert-butyl ether (MTBE) but also ethyl tert-butyl
      ether (ETBE), are added to gasoline in replacement of lead tetraethyl to enhance
      its octane index. Their addition also improves the combustion efficiency and
      therefore decreases the emission of pollutants (CO and hydrocarbons). On the
      other hand, MTBE, being highly soluble in water and recalcitrant to
      biodegradation, is a major pollutant of water in aquifers contaminated by MTBE
      supplemented gasoline during accidental release. MTBE was shown to be degraded
      through cometabolic oxidation or to be used as a carbon and energy source by a
      few microorganisms. We have summarized the present state of knowledge about the
      microorganisms involved in MTBE degradation and the MTBE catabolic pathways. The
      role of the different enzymes is discussed as well as the rare and recent data
      concerning the genes encoding the enzymes involved in the MTBE pathway. The
      phylogeny of the microorganisms isolated for their capacity to grow on MTBE is
      also described.

PMID- 16804693
TI  - Cloning and expression of manganese superoxide dismutase of the silkworm, Bombyx
      mori by Bac-to-Bac/BmNPV Baculovirus expression system.
AB  - Superoxide dismutase (SODs) are metalloenzymes that catalyze the dismutation of
      the superoxide anion to molecular oxygen and hydrogen peroxide and, thus, form a
      crucial part of the cellular antioxidant defense mechanism. In this paper, we
      used the total fat body RNA of silkworm, Bombyx mori L. to clone and sequence a
      648-bp Mn-SOD cDNA fragment through RT-PCR. Furthermore, a newly established Bac
      to-Bac/BmNPV Baculovirus expression system was used to overexpress the
      recombinant Mn-SOD enzyme in silkworm larvae. The hemolymph was collected from
      the infected larvae 96 h post-infection and subjected to a 12 % SDS-PAGE and
      Western blotting. A 18.0-kDa protein was visualized after rBacmid/BmNPV/SOD
      infection. The SOD enzyme activity was determined with a tetrazolium salt for
      detection of superoxide radicals generated by xanthine and xanthine oxidase and
      its peak appeared in 96 h post-infection with 2.7 times of the control larvae.
      The availability of large quantities of SOD that the silkworm provides should
      greatly facilitate the future research and testing of this protein for potential
      application in medicine.

PMID- 16804694
TI  - Dynamic changes in nahAc gene copy numbers during degradation of naphthalene in
      PAH-contaminated soils.
AB  - Many bacteria that degrade polycyclic aromatic hydrocarbons (PAHs) contain the
      nahAc gene that encodes a component of multimeric naphthalene dioxygenases.
      Because the nahAc gene is highly conserved, this gene serves as a potential
      biomarker for PAH degradation activity. The aim of this research was to examine
      the relationship between the rate of naphthalene degradation and the copy number
      of the nahAc gene in soils using conventional and real-time PCR. Four sets of
      degenerate primers for real-time PCR were designed based on the nahAc DNA
      sequences of 33 bacterial species. Before addition of naphthalene, copy numbers
      of the nahAc gene were below the detection limits of the assay at 5 x 10(3) copy
      numbers per gram of soil, but increased by over a thousand fold to 10(7) copies
      after 6 days of exposure to naphthalene vapors (approximately 30 ppm soil water
      concentration). Two unreported naphthalene dioxygenase homologs were found in the
      naphthalene-spiked soil by cloning and sequencing of the PCR products from the
      nahAc primers. Results of these experiments demonstrate the highly dynamic
      changes that occur in soil microbial communities after exposure to naphthalene
      and suggest that there is a direct relationship between gene copy numbers and
      degradation rates for naphthalene in PAH-contaminated soils.

PMID- 16804695
TI  - A hemolysin from the mushroom Pleurotus eryngii.
AB  - A monomeric 17-kDa hemolysin designated as eryngeolysin was isolated from fresh
      fruiting bodies of the mushroom Pleurotus eryngii, using a protocol that involved
      gel filtration on Superdex 75, ion exchange chromatography on Mono Q and gel
      filtration on Superdex 75. Its N-terminal sequence demonstrated striking homology
      to that of its counterparts ostreolysin from the oyster mushroom Pleurotus
      ostreatus and aegerolysin from the mushroom Agrocybe cylindracea. Its hemolytic
      activity was unaffected over the pH range 4.0-12.0, but no activity was observed
      at pH 13 and at and below pH 2. The hemolysin was stable between 0 and 30 degrees
      C. At 40 degrees C, only residual activity was detectable. At and above 50
      degrees C, activity was indiscernible. Eryngeolysin exhibited cytotoxicity toward
      leukemia (L1210) cells but not toward fungi. The hemolysin was inactivated by
      treatment with trypsin. It exhibited antibacterial activity against Bacillus sp.
      but not against other species. It inhibited basal as well as ConA-stimulated
      mitogenic response of murine splenocytes. N-Glycolyneuraminic acid was the only
      sugar capable of inhibiting the hemolytic activity. Eryngeolysin-induced
      hemolysis was osmotically protected by polyethylene glycol (PEG) 10000 with a
      mean hydrated diameter dose to 9.3 nm. However, no protection was offered by PEG
      10000 to the anti-mitogenic and antiproliferative activities of eryngeolysin. The
      susceptibility of erythrocytes from different classes of vertebrates to
      eryngeolysin was mammalian > avian > reptilian > piscine.

PMID- 16804696
TI  - Invasive aspergillosis in chronic granulomatous disease: report of 7 cases.

PMID- 16804697
TI  - Consultation of parents in actual end-of-life decision-making in neonates and
      infants.
AB  - The objective of this study was to assess how frequently end-of-life decisions
      (ELDs) with a possible or certain life-shortening effect in neonates and infants
      were discussed with parents, and to determine if consultation of parents was
      associated with the type of ELD, (clinical) characteristics of the patient, and
      socio-demographic characteristics of the physician. A retrospective study of all
      deaths of live born infants under the age of one year was conducted in Flanders,
      Belgium. For 292 of all 298 deaths in a 1-year period (between 1 August 1999 and
      31 July 2000) the attending physician could be identified and was sent an
      anonymous questionnaire. All cases with an ELD and containing information
      regarding the consultation of parents were included. The response rate was 87%
      (253/292). In 136 out of 143 cases, an ELD was made and information on the
      consultation of parents was obtained. According to the physician, the ELD was
      discussed with parents in 84% (114/136) of cases. The smaller the gestational age
      of the infant, the more the parental request for an ELD was explicit (p=0.025).
      When parents were not consulted, the ELD was based more frequently on the fact
      that the infant had no chance to survive and less on quality-of-life
      considerations (p=0.001); the estimated shortening of life due to the ELD was
      small in all cases, but significantly smaller (p<0.001) if parents were not
      consulted. It is concluded that the majority of parents of children dying under
      the age of one year are consulted in ELD-making, especially for decisions based
      on quality-of-life considerations (95.1%). Parents of infants with a small
      gestational age more often explicitly requested an ELD.

PMID- 16804698
TI  - [Pulmonary arterial hypertension in collagenoses: clinical features,
      epidemiology, pathogenesis, diagnosis and treatment].
AB  - Pulmonary arterial hypertension (PAH) is a severe vasculopathy, which is
      characterised by progressive narrowing and obliteration of the pulmonary
      arterioles and increased endothelin-1 levels. The increase of vascular resistance
      in the lung vessels leads to chronic pressure overload and to right heart
      failure, if untreated. PAH often occurs in association with rheumatic
      inflammatory diseases (e.g., in 15% of patients with systemic sclerosis (SSc),
      especially in the limited form or in CREST patients) and determines their
      prognosis: in advanced stages, untreated patients die within a short period.
      Therefore all SSc patients, particularly the newly diagnosed ones, should be
      screened for PAH with echocardiography. If PAH is suspected, a right heart
      catheter should be performed, and if PAH is confirmed, adequate treatment should
      be initiated. While few years ago lung transplantation was the only option for
      patients with severe PAH, in recent years enormous progress was seen in drug
      treatment. Today prostanoids (Ventavis) and the endothelin receptor antagonist
      bosentan (Tracleer) are available for patients with PAH in WHO/NYHA stage III:
      they have substantially improved the prognosis of PAH in the last years. Since
      few months, also the phosphodiesterase inhibitor sildenafil (Revatio) is
      available. The combination of drugs with different mode of action will likely
      further improve the prognosis of PAH patients.

PMID- 16804699
TI  - [Evidence-based therapy of Raynaud's syndrome].
AB  - Raynaud's syndrome has a prevalence of 3-5% in the general population. Despite
      its high frequency, the majority of available therapies have not been validated
      in randomized controlled trials. Effective therapies with a high level of
      evidence include the calcium channel blocker nifedipine. As analyzed by meta
      analyses, nifedipine showed improvement of the peripheral circulation, as well as
      reduction of both the intensity and frequency of attacks in patients with primary
      and secondary Raynaud's syndrome as compared to placebo. Similar results in a
      metaanalysis were obtained for intravenous infusions of iloprost in patients with
      secondary Raynaud's phenomenon associated with systemic sclerosis. In addition,
      intravenous infusions of iloprost improved healing of fingertip ulcers in
      patients with systemic sclerosis. Therapies with significant effects in single
      randomized controlled trials include angiotensin II-receptor type 1 antagonists
      (losartan), the calcium channel blockers felodipine und amlodipine, serotonin
      reuptake-inhibitors (fluoxetine) und phosphodiesterase-V-inhibitors (sildenafil,
      vardenafil). However, the results for these promising substances have to be
      confirmed in long-term trials with larger patient numbers.

PMID- 16804701
TI  - Curling during desiccation protects the foliose lichen Lobaria pulmonaria against
      photoinhibition.
AB  - This study aims to assess the photoprotective potential of desiccation-induced
      curling in the light-susceptible old forest lichen Lobaria pulmonaria by using
      chlorophyll fluorescence imaging. Naturally curled thalli showed less
      photoinhibition-induced limitations in primary processes of photosynthesis than
      artificially flattened specimens during exposures to 450 micromol m-2 s-1 in the
      laboratory after both 12- (medium dose treatment) and 62-h duration (high dose
      treatment). Thallus areas shaded by curled lobes during light exposure showed
      unchanged values of measured chlorophyll fluorescence parameters (FV/FM, PhiPS
      II), whereas non-shaded parts of curled thalli, as well as the mean for the
      entire flattened thalli, showed photoinhibitory limitation after light
      treatments. Furthermore, the chlorophyll fluorescence imaging showed that the
      typical small-scale reticulated ridges on the upper side of L. pulmonaria caused
      a spatial, small-scale reduction in damage due to minor shading. Severe dry-state
      photoinhibition readily occurred in flattened and light-treated L. pulmonaria,
      although the mechanisms for such damage in a desiccated and inactive stage are
      not well known. Natural curling is one strategy to reduce the chance for serious
      photoinhibition in desiccated L. pulmonaria thalli during high light exposures.

PMID- 16804700
TI  - [Systemic sclerosis - diagnosis and classification].
AB  - Systemic sclerosis (SSc) is a polymorphic and heterogenic systemic disorder with
      inflammation, fibrosis and vascular damage. Early diagnosis and classification
      may be difficult if disease expression is oligosymptomatic (undifferentiated),
      presenting with only Raynaud's phenomenon or limited scleroderma. Scleroderma
      specific antinuclear autoantibodies, which are present early and persistently in
      about 90% of the patients with SSc, play an important taxonomic role. Scleroderma
      specific findings in nailfold capillary microscopy are sensitive and predictive
      for evolving SSc. An algorithm will be presented for the diagnosis and
      classification of SSc using clinical, capillaroscopic and serologic criteria,
      which are also useful for mixed or special forms of SSc. The 6th Outcome Measures
      in Rheumatology Clinical Trials (OMERACT) conference proposed different outcome
      measurements for clinical studies, however, for daily clinical practice there is
      as yet no consensus on status indices for disease activity, disease related
      damage or suitable prognostic criteria.

PMID- 16804702
TI  - Changes in soil carbon and nitrogen cycling along a 72-year wildfire
      chronosequence in Michigan jack pine forests.
AB  - We investigated the changes in soil processes following wildfire in Michigan jack
      pine (Pinus banksiana) forests using a chronosequence of 11 wildfire-regenerated
      stands spanning 72 years. The objective of this study was to characterize
      patterns of soil nutrients, soil respiration and N mineralization with stand
      development, as well as to determine the mechanisms driving those patterns. We
      measured in situ N mineralization and soil respiration monthly during the 2002
      growing season and used multiple regression analysis to determine the important
      factors controlling these processes. Growing-season soil respiration rates ranged
      from a low of 156 g C/m2 in the 7-year-old stand to a high of 254 g C/m2 in the
      22-year-old stand, but exhibited no clear pattern with stand age. In general,
      soil respiration rates peaked during the months of July and August when soil
      temperatures were highest. We used a modified gamma function to model a temporal
      trend in total N mineralization (total N mineralization=1.853-0.276xagexe
      0.814xage; R2=0.381; P=0.002). Total N mineralization decreased from 2.8 g N/m2
      in the 1-year-old stand to a minimum value of 0.5 g N/m2 in the 14-year-old
      stand, and then increased to about 1.5 g N/m2 in mature stands. Changes in total
      N mineralization were driven by a transient spike in N turnover in the mineral
      soil immediately after wildfire, followed by a gradual accrual of a slow-cycling
      pool of N in surface organic horizons as stands matured. Thus, in Michigan jack
      pine forests, the accumulation of surface organic matter appears to regulate N
      availability following stand-replacing wildfire.

PMID- 16804703
TI  - Do high-tannin leaves require more roots?
AB  - The well-known deceleration of nitrogen (N) cycling in the soil resulting from
      addition of large amounts of foliar condensed tannins may require increased fine
      root growth in order to meet plant demands for N. We examined correlations
      between fine-root production, plant genetics, and leaf secondary compounds in
      Populus angustifolia, P. fremontii, and their hybrids. We measured fine-root (<2
      mm) production and leaf chemistry along an experimental genetic gradient where
      leaf litter tannin concentrations are genetically based and exert strong control
      on net N mineralization in the soil. Fine-root production was highly correlated
      with leaf tannins and individual tree genetic composition based upon genetic
      marker estimates, suggesting potential genetic control of compensatory root
      growth in response to accumulation of foliar secondary compounds in soils. We
      suggest, based on previous studies in our system and the current study, that
      genes for tannin production could link foliar chemistry and root growth, which
      may provide a powerful setting for external feedbacks between above- and
      belowground processes.

PMID- 16804704
TI  - Biodiversity and resilience of arthropod communities after fire disturbance in
      temperate forests.
AB  - Changes in ecosystem functions following disturbances are of central concern in
      ecology and a challenge for ecologists is to understand the factors that affect
      the resilience of community structures and ecosystem functions. In many forest
      ecosystems, one such important natural disturbance is fire. The aim of this study
      was to understand the variation of resilience in six functional groups of
      invertebrates in response to different fire frequencies in southern Switzerland.
      We measured resilience by analysing arthropod species composition, abundance and
      diversity in plots where the elapsed time after single or repeated fires, as
      determined by dendrochronology, varied. We compared data from these plots with
      data from plots that had not burned recently and defined high resilience as the
      rapid recovery of the species composition to that prior to fire. Pooling all
      functional groups showed that they were more resilient to single fires than to
      repeated events, recovering 6-14 years after a single fire, but only 17-24 years
      after the last of several fires. Flying zoophagous and phytophagous arthropods
      were the most resilient groups. Pollinophagous and epigaeic zoophagous species
      showed intermediate resilience, while ground-litter saprophagous and
      saproxylophagous arthropods clearly displayed the lowest resilience to fire.
      Their species composition 17-24 years post-burn still differed markedly from that
      of the unburned control plots. Depending on the fire history of a forest plot, we
      found significant differences in the dominance hierarchy among invertebrate
      species. Any attempt to imitate natural disturbances, such as fire, through
      forest management must take into account the recovery times of biodiversity,
      including functional group composition, to ensure the conservation of multiple
      taxa and ecosystem functions in a sustainable manner.

PMID- 16804705
TI  - Expression of the autofluorescent protein, DsRed2, in the recombinants of the
      ectomycorrhizal basidiomycete, Suillus grevillei, generated by Agrobacterium
      mediated transformation.
AB  - Recombinants were generated from the ectomycorrhizal basidiomycete, Suillus
      grevillei, through agroinfection using a binary vector carrying the hygromycin B
      resistance and the autofluorescent protein, DsRed2, markers. DsRed2 was driven by
      a cis-regulatory region of the glyceraldeyde-3-phosphate dehydrogenase gene (gpd)
      from the wood-rotting basidiomycete, Coriolus hirsutus, which contains promoters
      and 5' gpd sequences with first through fourth exons and expressed for the first
      time in Suillus spp. The transformation system and recombinants expressing an
      autofluorescent protein may be useful in genetic analysis of the symbiosis.

PMID- 16804706
TI  - Wheat nitrogen metabolism during grain filling: comparative role of glumes and
      the flag leaf.
AB  - The mobilization of nitrogen (N) compounds and the roles played by glumes and the
      flag leaf during grain filling were studied in bread wheat (Triticum aestivum L.
      cv. Florida) grown under field conditions. Glumes lost twice as much of their
      total N content as that lost by the flag leaf between the milk and early dough
      stages. In the flag leaf, glumes and grains, Glu, Asp, Ser and Ala accounted for
      85% of all the reductions in the free amino acid pool. Principal component
      analysis of free amino acid pools separated grains from the glumes and the flag
      leaf, suggesting grain specific regulations in the use of free amino acids in
      protein synthesis. In all three organs, no decrease in Gln was detected, probably
      due to steady glutamine synthetase (GS; EC 6.3.1.2) activities per soluble
      protein in both the flag leaf and glumes. Compared with the flag leaf, glumes
      presented relatively smaller amounts of the chloroplast GS associated isoform.
      This we show is due to a lower relative number of mesophyll cells in glumes as
      supported by the different anatomy and the cellular pattern of the GS
      immunolocalization. We argue that cellular distribution plays a key role in
      supporting metabolism to enable the various functions undertaken by glume tissue.

PMID- 16804707
TI  - Visual field and multifocal electroretinography and their correlations in
      patients on hydroxychloroquine therapy.
AB  - PURPOSE: To evaluate the effects of hydroxychloroquine on visual field and
      multifocal electroretinography (mfERG) and their correlations in patients taking
      hydroxychloroquine. METHODS: This was a cross-sectional study in which patients
      on hydroxychloroquine therapy underwent automated 10-2 threshold static visual
      field examination and mfERG recordings. Non-parametric unadjusted and age
      adjusted Spearman correlation coefficients rho were calculated between the
      cumulative dose of hydroxychloroquine and the visual field mean deviation (MD)
      and pattern standard deviation (PSD) values; and the mfERG response amplitudes
      and peak latencies. Correlation analysis was also performed between the visual
      field MD and PSD values and the mfERG response amplitudes and peak latencies.
      RESULTS: A total of 26 eyes in 13 patients were analyzed. The mean duration of
      hydroxychloroquine therapy was 4.9 years and the mean cumulative dose was 574 g.
      No significant correlation was found between the cumulative dose of
      hydroxychloroquine and the visual field MD and PSD values. There were significant
      correlations between the cumulative dose of hydroxychloroquine and mfERG N1 and
      P1 response amplitudes for the central rings (ring 1-3). The correlations between
      the dose of hydroxychloroquine and mfERG N1 and P1 response amplitudes were
      strongest for the paracentral ring 2 (rho =-0.63 and rho =-0.62, respectively, P
      = 0.001). Significant correlations were also found between the visual field MD
      values and mfERG response amplitudes of various ring eccentricities. CONCLUSIONS:
      In patients on hydroxychloroquine, mfERG response amplitude correlated with both
      the 10-2 visual field MD values and with the cumulative dose of
      hydroxychloroquine used. The use of mfERG can provide objective measurement of
      retinal function in patients on hydroxychloroquine and may provide supplementary
      quantitative information to visual field findings.

PMID- 16804708
TI  - Automated post hoc removal of power-line and CRT frame pulse contamination from
      retinal and cortical evoked potentials (EPs).
AB  - Recordings of the ERG, PERG, VEP and their multi-focal variants are occasionally
      contaminated with harmonic noise arising from the mains supply and CRT monitors.
      These noise contributions can be modelled as distorted sinusoids and identified
      by means of non-linear multiple regression and removed: no a priori estimates of
      number or frequency of noise sources are required. This approach is termed noise
      cancellation and does not constitute any form of notch filter: the fidelity of
      the underlying waveform is preserved. Here the simple theory is illustrated in
      artificial datasets and then applied to clinical examples of PERG and VEP. The
      programming language used throughout is MatLab R13SP3 (Mathworks UK Ltd.).

PMID- 16804709
TI  - Correlation between Bax overexpression and prion deposition in medulla oblongata
      from natural scrapie without evidence of apoptosis.
AB  - Although apoptosis has been implicated in the neuronal loss observed in prion
      diseases, the participation of apoptosis-related factors, like the Bcl-2 family
      of proteins, is still not clear. Moreover, there are conflicting data concerning
      the major role of apoptosis in the neuropathology associated with transmissible
      spongiform encephalopathies. Many studies have been developed in vitro or in
      experimentally infected animal models but, at present, little is known about this
      process in natural spontaneous and acquired prion diseases. In this work, the
      implication of Bax and Bcl-2 has been investigated by the analysis of their
      expression and protein distribution in medulla oblongata of naturally scrapie
      infected sheep. Moreover, their spatial relationship with PrP(Sc) deposition,
      neuronal vacuolation and neuropil spongiosis has also been analysed as well as
      the possible induction of neuronal apoptosis in this model. Real Time RT-PCR
      showed overexpression of the pro-apoptotic gene Bax in scrapie medullas, and
      immunohistochemistry confirmed its accumulation. No variation of Bcl-2 was
      observed at the level of gene expression or protein production. Bax distribution,
      PrP(Sc) deposition, neuronal vacuolation and spongiosis were quantified in
      different medulla oblongata nuclei and their spatial relationship was evaluated.
      Bax staining showed a positive correlation with prion deposition, suggesting that
      this factor is involved in prion neurotoxicity in our natural model. Despite Bax
      overexpression, neuronal apoptosis was revealed neither by TUNEL nor by
      immunohistochemical detection of the activated form of caspase-3. This lack of
      apoptosis could be attributed to the relatively low number of neurons in this
      area or to the existence of neuroprotective mechanisms in medulla oblongata motor
      neurons.

PMID- 16804710
TI  - Corticobasal degeneration with focal, massive tau accumulation in the subcortical
      white matter astrocytes.
AB  - We report two sporadic cases of tauopathy with unusual neuropathological
      features. The ages of the patients at death were 86 and 74 years, and the disease
      durations were 4 and 3 years, respectively. The former patient showed progressive
      dementia and amyotrophy (autopsy revealed that severe cervical spondylosis was
      responsible for the amyotrophy), and the latter showed progressive parkinsonism
      and dementia. The essential brain pathologies were similar to each other;
      although ballooned neurons and astrocytic tau lesions (astrocytic plaques) were
      present in the affected cerebral cortex, the most striking finding was focal,
      much heavier accumulation of tau in the subcortical white matter. Moreover,
      double-labeling immunostaining, as well as Gallyas-Braak electron and AT8
      immunoelectron microscopic studies strongly suggested that in the affected
      subcortical white matter, the accumulation of tau occurred mainly in the
      astrocytic processes. In the latter patient, for whom frozen brain tissue was
      available, immunoblotting of insoluble tau revealed a pattern compatible with
      that obtained from brain affected by typical corticobasal degeneration (CBD), and
      gene analysis of tau revealed no mutations, with a H1 haplotype. Finally, in both
      cases, the pathological diagnosis of CBD was considered to be appropriate.
      However, the tau pathology affecting the subcortical white matter astrocytes was
      very unusual for the disease.

PMID- 16804711
TI  - Does striatal pathology distinguish Parkinson disease with dementia and dementia
      with Lewy bodies?
AB  - The morphological differentiation of Parkinson disease with dementia (PDD) and
      dementia with Lewy bodies (DLB) is a matter of discussion. The objective of this
      study was to investigate the regional distribution of beta-amyloid (Abeta)
      plaques, alpha-synuclein (AS), and pathology in both disorders. The basal ganglia
      from 17 age-matched patients of PDD and DLB each were immunohistochemically
      examined with variable degrees of associated Alzheimer pathology using antibodies
      to Abeta, AS, and tau. DLB brains showed a significantly higher burden of
      (diffuse) amyloid plaques in the putamen and caudate nucleus and slightly more
      severe tau pathology than PDD brains despite similar neuritic Braak stages.
      Phases of Abeta development in DLB brains often, but inconsistently, correlated
      with both neuritic Braak stages and severity of striatal Abeta load, while these
      correlations were almost never seen in PDD cases with Alzheimer lesions. They
      also revealed a higher burden of AS-lesions (both Lewy neurites and Lewy bodies)
      than PDD cases that commonly had a paucity of all three types of lesion. The
      globus pallidus was virtually spared in both phenotypes. Differences in AS and
      Abeta pathologies and much less of tau lesions in the striatum support a
      morphologic distinction between PDD and DLB, which may be of pathophysiologic
      importance, but the causes of these differences are unclear.

PMID- 16804712
TI  - Peri-insular hemispherotomy in paediatric epilepsy.
AB  - OBJECTS: Outline the indications, investigation, surgical technique, pitfalls,
      complications and benefits of peri-insular hemispherotomy (PIH) in the surgical
      treatment of paediatric epilepsy. MATERIALS AND METHODS: This report is based on
      a consecutive series of 43 children who underwent PIH. Sixty percent were males;
      there were slightly more left-sided surgeries. Median interval between seizure
      onset and surgery was 5 years. In more than half the cases, the anatomical
      substrate was congenital. There were few complications: one death, one
      hydrocephalus and two anatomically remote haemorrhages. Ninety percent of the
      patients have remained in Engel's class I epilepsy outcome. CONCLUSIONS: There
      are clear indications for hemispherectomy in children. In some instances of
      incomplete deficit, timing of surgery remains a major concern. The less invasive
      approach to eliminate the influence of the diseased hemisphere, in our opinion,
      is with disconnective techniques of hemispherectomy, and among the latter, peri
      insular hemispherotomy provides, in our opinion, the best complications-benefits
      ratio.

PMID- 16804713
TI  - The role of magnetoencephalography in pediatric epilepsy surgery.
AB  - INTRODUCTION: Magnetoencephalography (MEG) is a new diagnostic imaging and brain
      mapping device that has been recently used in the context of pediatric epilepsy,
      epilepsy surgery, and neuronavigation. PRINCIPLES OF MAGNETOENCEPHALOGRAPHY: MEG
      allows for the placement of magnetic spike sources on a conventional magnetic
      resonance imaging scan, the so-called magnetic source imaging, so that the
      localization of epileptiform activity in a child can be determined. Considerable
      effort is placed on analyzing the configuration and number of spike waves by MEG
      that relate to a primary epileptiform discharge. Such MEG spike clusters are
      corroborated now by intraoperative invasive subdural grid monitoring that show
      good correlation in the majority of cases. Another important role of MEG relates
      to the mapping of critical regions of brain function using known paradigms for
      speech, motor, sensory, visual, and auditory brain cortex. FUTURE APPLICATIONS:
      When linked to standard neuronavigation devices, MEG brain mapping can be
      extremely helpful to the neurosurgeon approaching nonlesional epilepsy cases or
      lesional cases where the safest and most direct route to the surgical disease can
      be selected. As paradigms for brain mapping improve and as MEG software upgrades
      become more sensitive to analyzing all types of spike sources, MEG will play an
      increasingly important role in pediatric neurosurgery, especially for the child
      with intractable epilepsy.

PMID- 16804714
TI  - A report of nine newborns with congenital brain tumors.

PMID- 16804715
TI  - A report of nine newborns with congenital brain tumours.
AB  - BACKGROUND: Although rare, brain tumours represent one of the relatively larger
      groups of congenital neoplasias. Most studies on congenital neoplastic disease
      deal with several types of neoplasms and are dominated by leukaemias,
      retinoblastomas and systemic solid tumours. Few studies are dedicated to
      congenital brain tumours. We present nine newborns (four boys and five girls) who
      were diagnosed with congenital brain tumours during the 8-year period 1 January
      1992-31 December 1999 at our institution, which covers all paediatric neuro
      oncology cases for Eastern Denmark. EPIDEMIOLOGY: Two of the cases were referred
      from Western Denmark for surgery, and were therefore excluded from the
      calculation of incidence. During the same period, a total of 172 children below
      the age of 15 years were diagnosed as having primary central nervous system
      tumours. The seven remaining congenital cases thus represent 4% of all paediatric
      brain tumour cases in the area (95% confidence interval 1.7-8.3%). The population
      of the referral area is 2.383x10(6), and based on the total number of living
      births, the incidence of congenital brain tumour was calculated to be 2.9 per
      100,000 live births. The ages of the mothers were 28-33 years, corresponding to
      the present mean age of 31 years for Danish primipara. The gestational age varied
      between 35 and 42 weeks, and the birth weights were 3,044-4,790 g. RISK FACTORS:
      Two patients with p53-related glioblastoma multiforme (GBM) had relatives with
      p53-related neoplasms. In one case, the mother was treated for cancer of the
      ovary with surgery and chemotherapy 2 months before conception. CLINICAL
      FEATURES: In five of the cases, brain abnormality was suspected antenatally. The
      clinical features of the newborns were limited to enlarged head circumferences,
      associated hydrocephalus, and asymmetric skull growth. DIAGNOSIS AND TREATMENT:
      Three babies were treated with complete tumour resection. In the remaining six
      cases, a guided or open biopsy to obtain histology was made after CT/MRI imaging.
      The histological diagnoses were teratoma in four cases, GBM in two cases,
      anaplastic astrocytoma in two cases and, finally, haemangioma capillare in one
      case. OUTCOME: Four of the patients (44%) are still alive, including two patients
      with totally resected combined orbital/intracranial teratomas, one patient with a
      totally resected haemangioma and one patient with anaplastic astrocytoma who did
      not receive any treatment apart from supportive care. The survival lengths of the
      five neonates who died varied between 1 day and 51 days.

PMID- 16804716
TI  - Reconstruction of outer attic wall defects using bone pate: Long-term clinical
      and histological evaluation.
AB  - The objective was to evaluate the long-term clinical outcome of the bony outer
      attic wall reconstruction (scutumplasty) by using autogenous bone pate in a
      series of patients who underwent canal wall up (CWU) mastoidectomy for middle ear
      cholesteatoma. In addition, an histological analysis of bone pate graft specimens
      taken during the second-look procedure 12 months after the first surgery, was
      carried out. A series of 134 ears from 128 patients with cholesteatoma who
      underwent staged CWU mastoidectomy and attic reconstruction with bone pate,
      between 1995 and 2000 inclusive, was retrospectively analyzed. In ten randomly
      selected ears, biopsies from the newly built outer attic wall were taken during
      the second-look operation and were microscopically analyzed. At the second stage
      operation, the bone pate graft was found normal in 64.9% of cases. In 39 (29.1%)
      patients there was a remarkable hypertrophy of the bone pate which was
      subsequently thinned out by using a diamond burr. A partial resorption of the
      bone pate was observed in 4.4% of ears and a total resorption in 1.4%. Residual
      cholesteatoma was found in 13.4% of ears. At the last follow-up visit, recurrent
      cholesteatoma was observed in 5.2% of ears. Self cleaning attic retraction pocket
      occurred in 4.4% of ears. Twelve months after implantation, histologic
      examination on the newly built bone showed a well-structured bony tissue. In
      particular, osteoblasts lined bone trabeculae with signs of an active tissue
      remodeling. In conclusion, the reconstruction of the outer attic wall should be
      considered a fundamental step when performing a CWU procedure in order to prevent
      attic retractions and recurrences of cholesteatoma. In our experience, autogenous
      bone pate graft has demonstrated good long-term results in outer attic wall
      reconstruction being adaptable, well tolerated, stable and of low cost.

PMID- 16804717
TI  - Laryngeal leiomyosarcoma: a case report and review of the literature.
AB  - Laryngeal leiomyosarcoma (LLM) is a rare malignancy originating from the smooth
      muscles of blood vessels or from aberrant undifferentiated mesenchymal tissue.
      Histological diagnosis may be particularly difficult and correct diagnosis is
      based on immunohistochemical investigations and electron microscopy. A case
      report of a LLM in a 74-year-old man is presented. Direct laryngoscopy revealed a
      large glottic lesion causing airway compromise and an emergency tracheotomy was
      performed. Subsequent total laryngectomy confirmed the diagnosis of
      leiomyosarcoma. Lung metastases developed 8 months following treatment, despite
      the absence of local or regional recurrence, and the patient died 3 months later.
      A review of the English and French literature revealed 30 previous cases of LLM.
      Clinical presentation, histological diagnosis, and management of this rare
      malignancy are analyzed aiming to improve our knowledge regarding the best
      treatment modality.

PMID- 16804719
TI  - A nasal tooth associated with septal perforation: A rare occurrence.
AB  - Supernumerary teeth occur in a wide variety of sites, including the palate,
      mandibular condyle, coronoid process, orbit, maxillary antrum, and nasal cavity.
      Supernumerary teeth manifest in different ways depending on the site. Reported
      symptoms and signs associated with supernumerary teeth in the nasal cavity (nasal
      teeth) include facial pain, external nasal deformities, foul-smelling rhinorrhea,
      recurrent epistaxis, and oronasal fistula. Very rarely, septal perforation has
      been reported. We present a case in which eruption of a tooth into the nasal
      cavity was associated with nasal septal perforation. The tooth was extracted
      endoscopically.

PMID- 16804718
TI  - Evaluation of acute trismus by MRI: a case report. Bilateral peritonsillar
      cellulitis.
AB  - We describe a rare case of a bilateral peritonsillar cellulitis (PTC). The
      clinical presentation of fever, trismus and odynophagia was consistent with PTC,
      more evident on the right side; but the presence of bilateral tonsillar swelling
      and midline uvula confounded the diagnosis. In spite of the throat examination
      was performed with a great difficulty due to trismus, the T2 weighted fat
      saturated STIR magnetic resonance imaging (MRI) guided us to make the diagnosis
      and to start the intravenous antibiotic treatment immediately.

PMID- 16804720
TI  - Adjustments of prehension synergies in response to self-triggered and
      experimenter-triggered load and torque perturbations.
AB  - Humans are known to show anticipatory adjustments in the grip force prior to a
      self-generated or predictable action or perturbation applied to a hand-held
      object. We investigated whether humans can also adjust covariation of individual
      finger forces (multi-finger synergies) prior to self-triggered perturbations. To
      address this issue, we studied adjustments in multi-digit synergies associated
      with applied load/torque perturbations while the subjects held a customized
      handle steadily. The main hypothesis was that the subjects would be able to
      demonstrate the phenomenon of anticipatory covariation, that is changes in
      covariation patterns among digit forces and moments of force in anticipation of a
      perturbation, but only when the perturbation was triggered by the subjects
      themselves. Based on the principle of superposition (decoupled grasping force and
      resultant torque control), we also expected to see different adjustments in
      indices of multi-digit synergies stabilizing the total gripping force and the
      total moment of force. The task for the subjects (n = 8) was to return the
      initial handle position as quickly as possible after a perturbation, which
      consisted of removing one of three loads hanging from the handle. There were six
      experimental conditions: two types of perturbations (self-triggered and
      experimenter-triggered) by three positions of the load (left, center, and right).
      Three-dimensional forces and moments of force recorded from each digit contact
      were used for the analysis. Indices of covariation among digit forces and among
      moments of force, previously employed for studying motor synergies, were computed
      across trials. Positive values of the indices reflected negative covariations of
      individual digit forces and moments of force (their inter-compensatory changes)
      to stabilize the total force and moment acting on the handle. In steady-state
      conditions, subjects showed strong positive indices for both digit forces and
      digit moments. Under the self-triggered conditions, changes in the indices of
      digit force and moment covariation were seen about 150 ms prior to the
      perturbation, while such changes were observed only after the perturbation under
      the experimenter-triggered conditions. Immediately following a perturbation, the
      indices of force and moment covariation rapidly changed to negative revealing the
      lack of inter-compensation among the individual digit forces and moments. Later,
      both indices showed a recovery to positive values; the recovery was faster in the
      self-triggered conditions than in the experimenter-triggered ones. During the
      steady-state phase after the perturbation, the indices of force and moment
      covariation decreased and increased, respectively, as compared to their values
      during the steady-state phase prior to the perturbation. We conclude that humans
      are able to adjust multi-digit synergies involved in prehensile tasks in
      anticipation of a self-triggered perturbation. These conclusions speak against
      hypotheses on the organization of multi-element actions based on optimal control
      principles. Different changes in the indices of force and moment covariation
      after a perturbation corroborate the principle of superposition. We discuss
      relations of anticipatory covariation to anticipatory postural adjustments.

PMID- 16804721
TI  - A secondary metabolite biosynthesis cluster in Trichoderma virens: evidence from
      analysis of genes underexpressed in a mutant defective in morphogenesis and
      antibiotic production.
AB  - A transcriptional comparison of wild type and a secondary metabolite deficient
      Trichoderma virens mutant resulted in the identification of six genes similar to
      those involved in secondary metabolism in other fungi, including four cytochrome
      P450 genes, one O-methyl transferase and one terpene cylase. Four of the genes
      (three cytochrome P450s and the cyclase) are located as a cluster. Transcript
      levels of three of the P450 genes, the O-methyl transferase and the terpene
      cyclase were measured. These genes are underexpressed in the mutant, which lacks
      the major secondary metabolites produced by this strain, viridin and viridiol.
      Expression levels of clones from the differential library with similarity to
      fungal trehalose synthase and a hydrophobin were also underexpressed in the
      mutant, while a heat shock protein hsp98 homolog was not. Based on the gene
      expression pattern and associated secondary metabolite profile, along with
      similarity to other secondary metabolism pathways in related fungi, we predict
      that the cluster is associated with the production of a terpene. The terpene
      could be viridin. This is the first report on cloning of secondary metabolism
      related genes from T. virens, and of their organization in a cluster, in this
      biocontrol fungus.

PMID- 16804723
TI  - Neoadjuvant chemotherapy with S-1 and CDDP in advanced gastric cancer.
AB  - PURPOSE: This retrospective study evaluated the effects of neoadjuvant
      chemotherapy in advanced gastric cancer. METHODS: Between 2002 and 2005, we
      treated 14 patients with advanced gastric cancer (involvement of more than five
      nodes or tumor invasion into pancreas) and 25 patients with Stage III gastric
      cancer. The group of 14 patients with advanced gastric cancer received
      combination chemotherapy with S-1 and cis-diamminedichloroplatinum (CDDP) as a
      neoadjuvant chemotherapy (NAC). This regimen was repeated every 5 weeks for a
      total of 2-5 cycles. The 25 patients with Stage III gastric cancer was carried
      surgery alone (SA). All patients underwent extensive surgery, including
      gastrectomy, and D2 lymphadenectomy. The rate of response and overall survival in
      the two groups were compared. RESULTS: All patients of NAC group completed the
      planned regimens of chemotherapy and surgery. Patients of the NAC group had a
      response rate of 78.6% (95% confidence interval 57.1-100.0%). The most common
      adverse effect was leukocytopenia (42.9%). However, only four patients (28.6%)
      had upper Grade 2 leukocytopenia, and all recovered promptly. Postoperative
      complications were not significant differentiated between NAC and SA group of
      patients (7.2 vs. 4.0%). Patients in the NAC group had a significantly better
      survival than those in the SA group (P = 0.03). The median survival has not been
      reached after 26.9 months of median follow-up for patients in the NAC group. 1-,
      2-, and 3-year survival rates were 92.3, 92.3, and 61.5%, respectively. NAC was
      identified as an independent prognostic factor in all patients (P = 0.018).
      CONCLUSION: Neoadjuvant chemotherapy with TS-1 + CDDP improves the survival in
      patients with advanced gastric cancer.

PMID- 16804722
TI  - DeltaNp63 protein expression in uterine cervical and endometrial cancers.
AB  - PURPOSE: To investigate the significance of p63 expression in uterine cervical
      and endometrial cancers. MATERIALS AND METHODS: DeltaNp63 protein expression was
      studied in a variety of 127 cases of uterine cervical lesions (20 non-neoplastic
      cervices, 43 cervical intraepithelial neoplasia [CIN], 54 squamous cell
      carcinomas (SCCs), 40 adenocarcinomas, and 13 other histologic types) and 30
      endometrioid type of endometrial adenocarcinomas by using immunohistochemistry.
      One SCC cell line (ME-180) and one adenocarcinoma cell line (HeLa) were also
      included. RESULTS: In uterine cervix, the expression of DeltaNp63 was increased
      with progression of CIN, and positive in all SCCs, transitional cell carcinomas,
      and adenoid basal carcinoma, but negative in all adenocarcinomas. Adenosquamous
      cell carcinoma and mixed neuroendocrine and squamous cell carcinoma were positive
      in squamous component, but not in adenocarcinoma and neuroendocrine carcinoma
      components. ME-180 cell line was positive, whereas HeLa cell line was negative.
      Endometrioid type of endometrial adenocarcinomas showed a positive staining in
      glandular (26.7%) and squamous component. CONCLUSIONS: Immunohistochemical
      staining for DeltaNp63 is a powerful marker for squamous differentiation and
      useful in exclusion of glandular and neuroendocrine differentiation in uterine
      cervical cancers, but not always in endometrial cancers.

PMID- 16804724
TI  - Prognostic value of cell cycle regulatory proteins in muscle-infiltrating bladder
      cancer.
AB  - PURPOSE: The aims of this study were to investigate the expression levels of
      proteins involved in cell cycle regulation in specimens of bladder cancer and to
      correlate them with the clinicopathological characteristics, proliferative
      activity and survival. METHODS: Eighty-two specimens obtained from patients
      affected by muscle-invasive bladder cancer were evaluated immunohistochemically
      for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation
      index, Ki-67. The statistical analysis included Kaplan-Meier curves with log-rank
      test and Cox proportional hazards models. RESULTS: In univariate analyses, low Ki
      67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04)
      were associated to patient's overall survival (OS), but in multivariate models
      p21 did not reach statistical significance. When the combinations of the
      variables were assessed in two separate multivariate models that included tumour
      stage, grading, lymph node status, vascular invasion and perineural invasion, the
      combined variables p21/Ki-67 or p21/cyclin D1 expression were independent
      predictors for OS; in particular, patients with positive p21/high Ki-67 (P =
      0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival
      outcome. CONCLUSIONS: Important alterations in the cell cycle regulatory pathways
      occur in muscle-invasive bladder cancer and the combined use of cell cycle
      regulators appears to provide significant prognostic information that could be
      used to select the patients most suitable for multimodal therapeutic approaches.

PMID- 16804725
TI  - Fine mapping of the recessive genic male-sterile gene (Bnms1) in Brassica napus
      L.
AB  - A recessive genic male sterility (RGMS) system, S45 AB, has been developed from
      spontaneous mutation in Brassica napus canola variety Oro, and is being used for
      hybrid cultivar development in China. The male sterility of S45 was controlled by
      two duplicated recessive genes, named as Bnms1 and Bnms2. In this study, a NIL
      (near-isogenic line) population from the sib-mating of S45 AB was developed and
      used for the fine mapping of the Bnms1 gene, in which the recessive allele was
      homozygous at the second locus. AFLP technology combined with BSA (bulked
      segregant analysis) was used. From a survey of 2,560 primer combinations (+3/+3
      selective bases), seven AFLP markers linked closely to the target gene were
      identified, of which four were successfully converted to sequence characterized
      amplified region (SCAR) markers. For further analysis, a population of 1,974
      individuals was used to map the Bnms1 gene. On the fine map, Bnms1 gene was
      flanked by two SCAR markers, SC1 and SC7, with genetic distance of 0.1 cM and 0.3
      cM, respectively. SC1 was subsequently mapped on linkage group N7 using doubled
      haploid mapping populations derived from the crosses Tapidor x Ningyou7 and DH
      821 x DHBao 604, available at IMSORB, UK, and our laboratory, respectively.
      Linkage of an SSR marker, Na12A02, with the Bnms1 gene further confirmed its
      location on linkage group N7. Na12A02, 2.6 cM away from Bnms1, was a co-dominant
      marker. These molecular markers developed from this research will facilitate the
      marker-assisted selection of male sterile lines and the fine map lays a solid
      foundation for map-based cloning of the Bnms1 gene.

PMID- 16804726
TI  - [Bilateral corneal ulcers with hypopyon in a patient with lethal outcome].

PMID- 16804727
TI  - Automatic adjustment of pressure support by a computer-driven knowledge-based
      system during noninvasive ventilation: a feasibility study.
AB  - OBJECTIVE: To evaluate the feasibility of using a knowledge-based system designed
      to automatically titrate pressure support (PS) to maintain the patient in a
      "respiratory comfort zone" during noninvasive ventilation (NIV) in patients with
      acute respiratory failure. DESIGN AND SETTING: Prospective crossover
      interventional study in an intensive care unit of a university hospital.
      PATIENTS: Twenty patients. INTERVENTIONS: After initial NIV setting and startup
      in conventional PS by the chest physiotherapist NIV was continued for 45 min with
      the automated PS activated. MEASUREMENTS AND RESULTS: During automated PS minute
      volume was maintained constant while respiratory rate decreased significantly
      from its pre-NIV value (20+/-3 vs. 25+/-3 bpm). There was a trend towards a
      progressive lowering of dyspnea. In hypercapnic patients PaCO(2) decreased
      significantly from 61+/-9 to 51+/-2 mmHg, and pH increased significantly from
      7.31+/-0.05 to 7.35+/-0.03. Automated PS was well tolerated. Two system
      malfunctions occurred prompting physiotherapist intervention. CONCLUSIONS: The
      results of this feasibility study suggest that the system can be used during NIV
      in patients with acute respiratory failure. Further studies should now determine
      whether it can improve patient-ventilator interaction and reduce caregiver
      workload.

PMID- 16804728
TI  - The micro-organism responsible for central venous catheter related bloodstream
      infection depends on catheter site.

PMID- 16804729
TI  - [Overactive bladder--new definition, more patients!?].

PMID- 16804730
TI  - [Sacroplasty for the treatment of insufficiency fractures of the sacrum].
AB  - Sacral insufficiency fractures are an easily overlooked injury of the elderly,
      leading to severe and debilitating lower back pain. Percutaneous vertebroplasty
      with polymethylmethacrylate (PMMA) has become the treatment of choice for painful
      osteoporotic vertebral compression fractures. This is mainly due to the excellent
      results in pain relief, combined with the low morbidity of the procedure and the
      possibility of performing it in an outpatient setting. This well known technique
      can be transferred to the treatment of sacral insufficiency fractures for which
      no active therapy is currently available. This so-called sacroplasty was first
      reported in 2002 in a single case report. Six other patients with this indication
      have been reported in the Anglo-American literature to date. This article is the
      first description of this technique in the German literature. It compromises the
      description of two typical cases highlighting the difficulties in diagnosis,
      surgical technique and possible complications. Both patients were treated
      successfully and showed dramatic pain relief within several hours.

PMID- 16804732
TI  - Infection in primary hip arthroplasty after previous steroid infiltration.
AB  - Steroid Infiltration into arthritic joints is a common means of treating pain. It
      is also sometimes done to differentiate pain in the hip from that in the low back
      or knee. We performed a retrospective review of the notes of all patients who had
      undergone hip replacements in Wrightington Hospital under the care of the senior
      author (V.R.) from 1997 to 2004. We identified all patients who had at least 1
      year follow up after the procedure. The infection rates in the patients who had
      received an injection of steroid into the joint prior to hip replacement and in a
      matched cohort who had received no such intervention were compared. In the
      injected group there was no incidence of infection during the period of follow
      up. There was one case of infection in a patient who had not had an injection
      prior to the arthroplasty. There was also a case of superficial infection in a
      patient who had no steroid infiltration prior to surgery, which responded to
      antibiotics. Steroid injections are a valuable adjunct in the management of
      patients with arthritic joints. This review clearly identifies no increased risk
      of infection in patients who had received the injection prior to the operation.

PMID- 16804731
TI  - Orthodenticle and empty spiracles genes are expressed in a segmental pattern in
      chelicerates.
AB  - Members of the orthodenticle (otd/Otx) and empty spiracles (ems/Emx) gene
      families are head gap genes that encode homeodomain-containing DNA-binding
      proteins. Although numerous studies show their central role in developmental
      processes in brain specification, a surprisingly high number of other
      developmental processes have been shown to involve their expression. In this
      paper, we report the identification and expression of ems and otd in two
      chelicerate species: a scorpion, Euscorpius flavicaudis (Chactidae, Scorpiona,
      Arachnida, Euchelicerata) and a spider, Tegenaria saeva (Aranea, Arachnida,
      Euchelicerata). We show that both ems and otd are expressed not only in an
      anterior head domain but also along the entire anterior-posterior axis during
      embryonic development. The expression patterns for both genes are typically
      segmental and concern neurectodermal territories. During patterning of the
      opisthosoma, ems and otd are expressed in the lateral ectoderm just anterior to
      the limb bud primordia giving rise to respiratory organs and spinnerets (spider).
      This common pattern found in two divergent species thus appears to be a conserved
      character of chelicerates. These results are discussed in terms of evolutionary
      origin of respiratory organs and/or functional pathway recruitment.

PMID- 16804733
TI  - An algorithmic method for reducing conductance-based neuron models.
AB  - Although conductance-based neural models provide a realistic depiction of
      neuronal activity, their complexity often limits effective implementation and
      analysis. Neuronal model reduction methods provide a means to reduce model
      complexity while retaining the original model's realism and relevance. Such
      methods, however, typically include ad hoc components that require that the
      modeler already be intimately familiar with the dynamics of the original model.
      We present an automated, algorithmic method for reducing conductance-based neuron
      models using the method of equivalent potentials (Kelper et al., Biol Cybern
      66(5):381-387, 1992) Our results demonstrate that this algorithm is able to
      reduce the complexity of the original model with minimal performance loss, and
      requires minimal prior knowledge of the model's dynamics. Furthermore, by
      utilizing a cost function based on the contribution of each state variable to the
      total conductance of the model, the performance of the algorithm can be
      significantly improved.

PMID- 16804736
TI  - Cytomegalovirus infection of a cutaneous ulcer in a patient with ANCA-positive
      vasculitis.
AB  - This case describes a patient in whom cytomegalovirus (CMV) infected a
      preexisting ulcer. The patient was immune-suppressed because of treatment for
      Wegener's granulomatosis. Specific antiviral therapy was delayed because of
      uncertainty as to the role of CMV, but the infection cleared and the ulcer
      improved promptly on institution of valganciclovir.

PMID- 16804735
TI  - Using myoelectric signal parameters to distinguish between computer workers with
      and without trapezius myalgia.
AB  - Complaints of chronic trapezius muscle pain among computer workers have increased
      in prevalence during the last decade. Currently there is no clear understanding
      of the pathophysiological mechanisms involved in affected muscles. The major
      objective of this work was to determine if measurable electrophysiological
      differences exist between the trapezius muscles in individuals suffering from
      trapezius myalgia (TM) and occupation-matched pain-free control subjects.
      Myoelectric signal (MES) data were recorded from the upper trapezius muscle while
      subjects with and without myalgia performed a standardized series of postural and
      arm-holding tasks. MES variables reflecting muscle fatigue, muscle tension and
      motor control strategies were analyzed to determine their potential ability to
      distinguish between the two groups. One variable, RestTime, was found to be
      significantly different between the groups but it was not specific enough to
      predict group association. A multivariate logistic regression analysis yielded a
      model that separated the two groups with better than 70% sensitivity and 70%
      specificity. The variables included in the model reflect differences in trapezius
      muscle activity between the groups, particularly related to motor control and/or
      active muscle tension, but not fatigue. The model was tested using a small sample
      of new data, which again produced a good sensitivity (85.7%) but not specificity
      (42.9%). To the authors' knowledge, this is the first objective MES-based model
      that has successfully classified subjects with or without TM based on a simple
      clinical test. Further work with this model might result in understanding the
      pathophysiology of TM, assisting with clinical diagnosis, and testing the effect
      of various treatment interventions.

PMID- 16804737
TI  - Celiac disease in a patient with systemic lupus erythematosus: a case report and
      review of literature.
AB  - Celiac disease (CD) is an inflammatory condition of the gut with a known
      autoimmune pathogenesis. Many similarities exist between the pathogenesis of CD
      and systemic lupus erythematosus (SLE); it is still unknown whether there is an
      association. There are 13 case reports in the literature of both diseases
      occurring simultaneously. We report another patient who was diagnosed with SLE
      and 8 years later, developed CD. A review of the literature is also presented.

PMID- 16804740
TI  - Phenolics and antioxidative activities in narrow-leafed lupins (Lupinus
      angustifolius L.).
AB  - Eight lupin (Lupinus angustifolius L.) genotypes grown at four locations in south
      central Alberta in 2004 were evaluated for variability in phenolic constituents
      and antioxidant activity measured by a photochemiluminescence assay. Genotype was
      the main source of variation for content of phenolic compounds and antioxidant
      activities. Phenolic compounds in genotypes varied minimally from 11.9 to 14.7 mg
      catechin equivalent and 4.15 to 4.95 mg rutin equivalent g(-1) lupin for total
      phenolic and flavonoid contents, respectively. Lupin genotypes exhibited weak
      antioxidant activity based on water-soluble substances (ACW) of 0.54 to 1.07
      micromole Trolox equivalent antioxidant capacities (TEAC)/g with lag time ranging
      from 70 to 153 s and an antioxidant index of 6.7 to 14.5 and 1.9 to 3.3 micromole
      TEAC/g based on measurements of lipid-soluble substances (ACL). Antioxidant
      activity of lupin genotypes was not related to phenolic contents of seeds.

PMID- 16804739
TI  - A randomized study of two different information-based interventions on the
      management of osteoporosis in minimal and moderate trauma fractures.
AB  - INTRODUCTION: Despite the high risk for subsequent fracture following an initial
      osteoporotic fracture, the majority of subjects with minimal trauma fractures
      receive no treatment for osteoporosis. The primary aim of this investigation was
      to determine whether an information-based intervention could change post-fracture
      management of osteoporosis. A secondary aim was to define participant- and doctor
      related barriers to osteoporosis management. METHODS: Consecutive fracture
      patients (n=254) from the outpatient fracture clinic at St Vincent's Hospital,
      Sydney were interviewed over a 15-month period (February 2002-July 2003).
      Fracture risk factors, prior investigation and treatment for osteoporosis were
      collected at baseline. Participants were initially contacted after 3 months to
      ascertain follow-up management. All those not investigated or treated by their
      primary care physician were then randomized to either a personalized letter or
      the same letter plus an offer of a free bone mineral density (BMD) test.
      Participants were contacted after 9 months to record further investigations or
      treatment for osteoporosis. RESULTS: Less than 20% of the participants had a
      primary care physician follow-up 3 months after the fracture, leaving 159 who
      were randomized to a personalized letter (n=79) and a personalized letter plus
      the offer of a free BMD test (n=80). There was a significant increase in the
      number of people investigated for osteoporosis in the group receiving the letter
      plus BMD offer [38% (letter + BMD) vs. 7% (letter only); p=0.001). A high
      proportion of those tested had low BMD (49% osteopenia and 17% osteoporosis).
      However, the rates of treatment in both groups were very low (6%). Furthermore,
      even among the few individuals (23%) who contacted their primary care physician,
      only 25% were recommended treatment. The belief that the fracture was
      osteoporotic was an independent predictor of having a BMD test, a primary care
      physician follow-up and treatment. Other independent predictors were age over 50
      years for a primary care physician follow-up, female sex for having a BMD test
      and having had a BMD test for treatment. CONCLUSION: This study demonstrates that
      an information-based intervention led to a modest increase in the proportion of
      people investigated for osteoporosis; however. there was no significant effect on
      treatment rates. The offer of a free BMD assessment was associated with a
      significantly higher rate of investigation than a personalized letter alone (odds
      ratio: 8.5; 95% confidence interval: 3.1-24.5), but this investigation did not
      affect treatment rate. The low uptake of either a BMD or a visit to a primary
      care physician together with low rates of treatment recommendation even among
      people who contacted their primary care physician reflects significant
      participant and doctor-related barriers to osteoporosis management.

PMID- 16804738
TI  - Effects of rheumatoid factor isotypes on disease activity and severity in
      patients with rheumatoid arthritis: a comparative study.
AB  - The value of rheumatoid factor (RF) isotypes for assessing rheumatoid arthritis
      (RA) remains debatable. In this study, we have examined the relationships between
      RF isotypes and disease activity and severity in RA patients. Sixty-two patients
      with RA, 48 women and 14 men, were studied. RF was measured by nephelometry (RF
      N) and IgG-, IgA-, and IgM-RF isotypes were measured using enzyme-linked
      immunosorbent assay. Serum C-reactive protein and erythrocyte sedimentation rate
      were also determined. The patients were classified according to disease activity,
      joint damage, functional status, and presence of pulmonary involvement,
      rheumatoid nodule, and secondary Sjogren's syndrome. Although the patients with
      active disease had significantly higher IgA-RF and IgM-RF levels compared to
      inactive patients, IgA-RF and IgM-RF were not found to be independently
      associated with disease activity in multivariate analysis. In patients with
      severe joint damage, IgA-RF and RF-N were significantly higher than those of the
      other patients. Multiple regression analysis showed that IgA-RF was the unique
      variable independently associated to severe joint damage. The patients with class
      III and IV functional index had significantly higher IgM-RF, IgA-RF, and RF-N
      levels compared to the patients with class I and II functional index; however,
      RFs were not significantly associated with functional status in multivariate
      analysis. IgA-RF and IgM-RF were significantly associated with pulmonary
      involvement and rheumatoid nodule, respectively. No significant associations were
      found between RF isotypes and secondary Sjogren's syndrome. Our results suggest
      that the clinical usefulness of IgA and IgM isotypes is better than RF-N.
      Elevated IgA-RF may be a marker of erosive disease. The usefulness of RF isotypes
      for monitoring disease activity or functional status appears to be limited.

PMID- 16804741
TI  - Effect of low storage temperature on some of the flavour precursors in garlic
      (Allium sativum).
AB  - Garlic (Allium sativum) cloves were stored at ambient temperature and 4 degrees C
      for periods up to six months to establish the effect of position of the
      individual clove within the bulb and of low storage temperature on the
      composition of several flavours precursors and other organic sulphur compounds,
      measured by gradient High Pressure Liquid Chromatography. Levels of alliin, gamma
      glutamyl allyl cysteine sulphoxide and gamma glutamyl isoallyl cysteine
      sulphoxide were statistically significantly higher in outer than in inner cloves.
      There was no statistically significant change in levels of alliin, the major
      flavour precursor, in cloves stored at 4 degrees C, remaining in the average
      range 17.5+/-3.8-39.1+/-7.5 mM. However, isoalliin increased significantly during
      storage at 4 degrees C, rising from an average 0.6+/-0.2 mM (outer cloves) --
      0.7+/-0.4 mM (inner cloves) to 7.1+/-1.7 mM (outer cloves) -- 4.1+/-0.7 mM (inner
      cloves). A decline in other sulphur-containing compounds, most likely to be the
      peptides gamma-glutamyl allylcysteine sulphoxide and gamma-glutamyl
      isoallylcysteine sulphoxide, occurred at the same time and possibly contributed
      to the increase in the flavour precursor compounds. The degree of chemical
      changes during storage will be of interest to the food and pharmaceutical
      industries.

PMID- 16804742
TI  - Overexpression of lysyl oxidase to increase matrix crosslinking and improve
      tissue strength in dermal wound healing.
AB  - In this study, we aimed to increase crosslinking in collagen and elastin in the
      extracellular matrix through overexpression of lysyl oxidase (LO) in order to
      improve mechanical strength in dermal wounds during healing. We had used a gene
      activated matrix (GAM) approach to locally deliver plasmid DNA (pDNA) complexed
      with polyethylenimine (PEI) in collagen gels at the wound site for localized and
      sustained transfection of cells involved in the healing process. We first
      demonstrated in vitro that PEI-pDNA complexes in collagen gels could be taken up
      and expressed by cultured fibroblasts for at least 20 days. In vitro studies
      showed that fibroblast-seeded GAMs with the LO transgene exhibited over a 3-fold
      increase in mechanical strength as compared with a green fluorescent protein
      (GFP)-transgene control. Addition of an inhibitor of LO abolished this increase.
      We applied this system in a rat dermal wound healing model and showed that
      treatment with LO-producing GAMs led to significantly enhanced mechanical
      strength of the wound site.

PMID- 16804743
TI  - Estimation of cardiac bidomain parameters from extracellular measurement: two
      dimensional study.
AB  - Cardiac tissue conductivity measurements can be used to assess the electrical
      substrate underlying normal and abnormal wavefront propagation. We describe a
      method of solving the inverse cardiac bidomain model to estimate average
      longitudinal and transverse intra and extra-cellular conductivities and fiber
      angle relative to an electrode array placed arbitrarily on the epi- or
      endocardial surface. A Newton-Raphson reconstruction method and two Tikhonov-type
      regularizations were able to stably identify conductivities and fiber angles in
      tissue models having anisotropies similar to those in real cardiac tissue. The
      reconstruction methods were tested with data from increasingly realistic two
      dimensional cardiac bidomain models and performed well both when measurement
      noise was added, and when simulated experimental and forward model matching was
      diminished. This approach may be a suitable basis for continuous monitoring of
      myocardial condition in-vivo via a catheter based electrode array.

PMID- 16804744
TI  - Coming out, visibility, and creating change: empowering lesbian, gay, and
      bisexual people in a rural university community.
AB  - Personal and professional challenges faced in encouraging the development of a
      gay community in a rural university setting are described. Community
      psychologists who are lesbian, gay, or bisexual (LGB) must assess their
      willingness to be open and the roles they can play in developing helping
      resources. These issues concern how to encourage the empowerment of others while
      maintaining a collaborative role in a situation of major personal investment. Two
      specific challenges-developing informal helping resources for local LGB people
      and fostering institutional and policy changes to make the university a safer
      place for LGB faculty, staff, and students-are described. Community psychologists
      must consider personal risk when they become involved in empowerment efforts with
      this population.

PMID- 16804745
TI  - Desired attributes of evidence assessments for evidence-based practices.
AB  - In this paper we describe three approaches to assessing evidence for stakeholders
      interested in evidence-based practices: narrative reviews, systematic reviews
      (including meta-analyses), and registries. We then compare the approaches in
      terms of the degree to which they posses desired attributes of evidence
      assessments. Our review suggests that hybrid approaches that combined the best
      features of all three should be pursued to further the use of evidence-based
      practices, and that such hybrids are possible given the capacity of the World
      Wide Web. We conclude by stressing the need for empirical research on evidence
      assessments.

PMID- 16804746
TI  - Predictors of condom use self-efficacy in an ethnically diverse university
      sample.
AB  - A multitude of factors influence condom use self-efficacy, including age, gender,
      ethnicity, condom use attitudes and barriers, sexual experience, and partner
      characteristics. The current study integrated past research by evaluating these
      factors in a large, ethnically diverse university sample of women and men
      (N=665). The role of gender on condom use and sexuality variables was assessed
      across ethnic groups. Hierarchical linear regressions were then calculated to
      explain levels of condom use self-efficacy using the hypothesized sexual
      predictors in nonvirgin, sexually active, and recent condom use subsamples.
      Predictors explained 18-45% of variance in condom use self-efficacy. Findings
      suggest that a few key variables accounted for the majority of variance in condom
      use self-efficacy: condom use attitudes, condom use barriers, satisfaction with
      sexual communication, anticipated number of sexual partners, one-time sexual
      encounters, and ethnic identity. Significant gender differences emerged in condom
      use self-efficacy, condom use attitudes, and condom use behaviors. Ethnic
      differences were found in range of sexual experience and sexual partner
      characteristics. It is recommended that future studies examining sexual risk
      behavior incorporate the diverse sexual factors that affect condom use self
      efficacy.

PMID- 16804747
TI  - Coming-out across the life course: implications of age and historical context.
AB  - Effects of age and the calendar year when individuals first self-identified as
      gay, lesbian, or bisexual on their sexual orientation identity development were
      examined in a large community sample (N=767, 47% female, 18-74-years-old). These
      2 variables were used to examine the timing and sequencing of 7 coming-out
      experiences: first awareness of same-sex attraction; first sexual experiences
      with opposite-sex partners; first sexual experiences with same-sex partners; self
      identification as gay, lesbian, or bisexual; disclosure to someone other than a
      parent; disclosure to mother; and disclosure to father. The significant effects
      of age revealed that self-identification in adolescence as opposed to adulthood
      was associated with an overall young coming-out trajectory for all milestone
      experiences, which occurred in both earlier and recent historical contexts.
      Adolescents as opposed to adult self-identifiers were also more likely to
      demonstrate identity-centered sequences in which self-identification preceded
      same-sex sexual experiences, and fewer of these individuals had any heterosexual
      experience. Significant historical context effects indicated recent trends toward
      younger disclosure of orientation to others and to parents, greater likelihood of
      an identity-centered sequence, and younger ages for first heterosexual but not
      same-sex, sexual experiences. Among women, there was a recent trend toward
      greater likelihood of having a bisexual identity milestone. In general, the
      maturational effects were independent of historical context, with the exception
      that only adolescent self-identifiers who came out recently disclosed to others
      and to parents at an average age younger than 18 years. These developmental and
      historical trends expand on the stage-sequential framework to show how the
      process of sexual orientation identity development is driven by maturational
      factors as well as social changes.

PMID- 16804748
TI  - A note on the power to detect transmission distortion in parent-child trios via
      the transmission disequilibrium test.
AB  - Transmission distortion refers to deviation from the normal 50:50 transmission of
      alleles from parents to offspring. Identification of genomic regions which
      undergo distortion is necessary for the correct interpretation of linkage and
      association studies, since tests of linkage using affected relative pairs and
      family based tests of association will yield spurious results in the presence of
      transmission distortion. With the increasing availability of genome-wide high
      density SNP data (e.g. from the International HapMap project), identification of
      these loci is now a real possibility. Here we present an analytical formula which
      demonstrates that the power to detect transmission distortion is a simple
      function of the number of heterozygous parents in the sample and the level of
      distortion at the locus. Our results indicate that whilst it will be possible to
      identify loci undergoing major levels of distortion using tens or hundreds of
      trios, large sample sizes in the order of tens of thousands of trios will be
      necessary to detect minor levels of distortion with appreciable power. The
      corollary is that genome-wide searches are unlikely to identify loci where the
      level of distortion is small, although they may serve to identify interesting
      regions worthy of follow up.

PMID- 16804750
TI  - Conflicting messages: how criminal HIV disclosure laws undermine public health
      efforts to control the spread of HIV.
AB  - Twenty-three U.S. states currently have laws that make it a crime for persons who
      have HIV to engage in various sexual behaviors without, in most cases, disclosing
      their HIV-positive status to prospective sex partners. As structural
      interventions aimed at reducing new HIV infections, the laws ideally should
      complement the HIV prevention efforts of public health professionals.
      Unfortunately, they do not. This article demonstrates how HIV disclosure laws
      disregard or discount the effectiveness of universal precautions and safer sex,
      criminalize activities that are central to harm reduction efforts, and offer, as
      an implicit alternative to risk reduction and safer sex, a disclosure-based HIV
      transmission prevention strategy that undermines public health efforts. The
      article also describes how criminal HIV disclosure laws may work against the
      efforts of public health leaders to reduce stigmatizing attitudes toward persons
      living with HIV.

PMID- 16804749
TI  - Assessing antiretroviral adherence via electronic drug monitoring and self
      report: an examination of key methodological issues.
AB  - We explored methodological issues related to antiretroviral adherence assessment,
      using 6 months of data collected in a completed intervention trial involving 136
      low-income HIV-positive outpatients in the Bronx, NY. Findings suggest that
      operationalizing adherence as a continuous (versus dichotomous) variable and
      averaging adherence estimates over multiple assessment points (versus using only
      one) explains greater variance in HIV-1 RNA viral load (VL). Self-reported
      estimates provided during a phone interview accounted for similar variance in VL
      as EDM estimates (R (2) = .17 phone versus .18 EDM). Self-reported adherence was
      not associated with a standard social desirability measure, and no difference in
      the accuracy of self-report adherence was observed for assessment periods of 1-3
      days. Self-reported poor adherence was more closely associated with EDM adherence
      estimates than self-reported moderate and high adherence. On average across
      assessment points, fewer than 4% of participants who reported taking a dose of an
      incorrect amount of medication.

PMID- 16804751
TI  - Mental representations of attachment in identical female twins with and without
      conduct problems.
AB  - Insecure mental representations of attachment, a nearly invariant feature of
      cluster B personality disorders, have never previously been studied in twins. We
      conducted the Adult Attachment Interview (AAI) on 33 pairs of monozygotic (MZ)
      female twins reared together as an initial exploration of causal influences on
      mental representations of attachment. As predicted by attachment theory, we
      observed substantial twin-twin concordance for attachment security (odds ratio
      13.8; P = 0.001), a similar level of concordance between twins and their non-twin
      siblings, and an inverse relationship between attachment security and current
      level of aggression (P = 0.01). These data indicate that there are minimal
      effects of non-shared environmental influences (or measurement error) on
      attachment classifications derived from the AAI. In this sample of twins with and
      without histories of Conduct Disorder, mental representations of attachment
      appear to be highly familial, i.e., strongly influenced by either shared
      environmental factors, genetic factors, or both.

PMID- 16804752
TI  - Mass spectrometrical analysis of galectin proteins in primary rat cerebellar
      astrocytes.
AB  - Galectins are a family of animal lectins with specificity for beta-galactosides
      and are involved in a host of cellular activities, ranging from development to
      cancer. The molecules are expressed by neural and non-neural cells
      intracellularly as well as extracellularly. Using two-dimensional gel
      electrophoresis coupled to tandem mass spectrometry, the present work aimed to
      identify and characterize galectins in primary rat cerebellar astrocytes. The
      protein-chemical method identified nine spots representing two members of the
      galectin family, namely galectin-1 and galectin-3. These findings suggest that
      high abundant expression of galectin in astrocytes is limited to the two abundant
      galectin family members. As these family members are linked to human astrocytic
      tumors, their reliable detection in astrocytes by proteomic techniques would
      enable us to further understand their role in neural development, injury, and
      regeneration in general and astrocytoma in particular.

PMID- 16804753
TI  - Melatonin decreases nitric oxide production, inducible nitric oxide synthase
      expression and lipid peroxidation induced by Venezuelan encephalitis equine virus
      in neuroblastoma cell cultures.
AB  - Increased expression of inducible nitric oxide synthase has been shown in murine
      Venezuelan equine encephalitis (VEE) virus infection. In this experimental model,
      melatonin (MTL) treatment has shown to be beneficial. The aim of this study was
      to determine the effect of VEE virus on the nitric oxide (NO) production and
      lipid peroxidation in neuroblastoma cell cultures, and to investigate the role of
      MTL during cell-virus interaction. Neuroblastoma cells were co-cultured with VEE
      virus and treated with MTL at doses ranging from 0 to 1.8 mM, for 6, 12, 24 and
      48 h. NO and lipid peroxidation were measured in culture supernatants and in the
      cellular content by nitrite concentration and thiobarbituric acid assay,
      respectively. Expression of inducible nitric oxide synthase (iNOS) was determined
      by indirect immunofluorescence. Increased production of NO and lipid peroxidation
      products were found in supernatants and cellular contents of VEE virus treated
      cultures. Both NO and lipid peroxidation were decreased by MTL treatment in a
      time dependent manner. Increased iNOS expression was observed in VEE virus
      infected cultures that was reduced by MTL treatment. These results could be
      related to the beneficial role of MTL in the VEE experimental disease and address
      the possible therapeutic potential of the hormone in human VEE virus infection.

PMID- 16804754
TI  - Activity of lactate dehydrogenase in serum and cerebral cortex of immature and
      mature rats after hypobaric hypoxia.
AB  - In our previous studies we have found both an increase of lipid peroxidation
      damage (expressed as levels of thiobarbituric acid-reactive substances) in brain
      and plasma lactate concentration in 21-day-old rats after a 30-min exposure to
      hypobaric hypoxia. Pretreatment of rats with L-carnitine decreased both
      parameters. The aim of our present study was to determine if the L-carnitine
      dependent decrease of plasma lactate could be due to a modification of lactate
      dehydrogenase (LDH) activity. We followed brain and blood serum LDH activity of
      14-, 21- and 90-day-old Wistar rats. We found an increase of brain LDH activity
      with age. However, we did not observe any significant differences in LDH activity
      after exposure to hypobaric hypoxia or L-carnitine pretreatment. In contrast to
      brain, serum LDH activity did not show any clear age-dependence. The hypoxia
      exposure increased LDH activity of 21-day-old rats only. Pretreatment of rats
      with L-carnitine decreased serum LDH activity of 21- and 90-day-old rats probably
      due to membrane stabilizing role of L-carnitine. In conclusions, acute hypobaric
      hypoxia and/or L-carnitine pretreatment modified serum but not brain LDH
      activity.

PMID- 16804755
TI  - Regional variations of 5HT concentrations in Rorasg (staggerer) mutants.
AB  - Ataxic Rora(sg) (staggerer) mouse mutants, containing a deletion of the Rora gene
      which encodes a retinoid-like nuclear receptor, were compared to non-ataxic
      controls for concentrations of 5-hydroxytryptamine (HT), its main metabolite (5
      hydroxy-indole acetic acid, 5HIAA), and its precursor (tryptophan) in cerebellum,
      brainstem, and forebrain. In Rora(sg) cerebellum, 5HT concentrations increased
      relative to controls, while tryptophan concentrations decreased. 5HIAA
      concentrations increased in mutant cerebellum and brainstem, but the 5HIAA/5HT
      ratio declined only in cerebellum. These results indicate that 5HT turnover
      decreased in cerebellum of an ataxic mutant, perhaps indicative of presynaptic
      accumulation and compromised neurotransmission and susceptible to be modified by
      5HT pharmacotherapy.

PMID- 16804756
TI  - Exogenous pleiotrophin applied to lesioned nerve impairs muscle reinnervation.
AB  - Pleiotrophin (PTN) is a heparin-binding growth factor involved in nerve
      regeneration after peripheral nerve injury. After crush injury, PTN is found in
      distal nerve segments in several non-neural cell types, including Schwann cells,
      macrophages, and endothelial cells, but not in axons. To further clarify the role
      for PTN in nerve regeneration, we investigated the effects of PTN applied to
      lesioned peripheral nerve in vivo. PTN in a dose of 1 mg/kg impaired muscle
      reinnervation. Thus, gastrocnemius muscle failed to recover its contractile
      properties as assessed by in situ maximal isometric tetanic force. PTN also
      decreased non-neural cell densities and delayed macrophage recruitment in the
      distal crushed nerve. These results are discussed in the light of recent evidence
      that PTN is a multifunctional polypeptide.

PMID- 16804757
TI  - Effect of 7-nitroindazole sodium on the cellular distribution of neuronal nitric
      oxide synthase in the cerebral cortex of hypoxic newborn piglets.
AB  - Cerebral hypoxia results in generation of nitric oxide (NO) free radicals by
      Ca(++)-dependent activation of neuronal nitric oxide synthase (nNOS). The present
      study tests the hypothesis that the hypoxia-induced increased expression of nNOS
      in cortical neurons is mediated by NO. To test this hypothesis the cellular
      distribution of nNOS was determined immunohistochemically in the cerebral cortex
      of hypoxic newborn piglets with and without prior exposure to the selective nNOS
      inhibitor 7-nitroindazole sodium (7-NINA). Studies were conducted in newborn
      piglets, divided into normoxic (n = 6), normoxic treated with 7-NINA (n = 6),
      hypoxic (n = 6) and hypoxic pretreated with 7-NINA (n = 6). Hypoxia was induced
      by lowering the FiO(2) to 0.05-0.07 for 1 h. Cerebral tissue hypoxia was
      documented by decrease of ATP and phosphocreatine levels in both the hypoxic and
      7-NINA pretreated hypoxic groups (P < 0.01). An increase in the number of nNOS
      immunoreactive neurons was observed in the frontal and parietal cortex of the
      hypoxic as compared to the normoxic groups (P < 0.05) which was attenuated by
      pretreatment with 7-NINA (P < 0.05 versus hypoxic). 7-NINA affected neither the
      cerebral energy metabolism nor the cellular distribution of nNOS in the cerebral
      cortex of normoxic animals. We conclude that nNOS expression in cortical neurons
      of hypoxic newborn piglets is NO-mediated. We speculate that nNOS inhibition by 7
      NINA will protect against hypoxia-induced NO-mediated neuronal death.

PMID- 16804758
TI  - Regulation of norepinephrine release from isolated bovine irides by histamine.
AB  - In the present study, we investigated the effect of histamine on sympathetic
      neurotransmission from isolated, superfused bovine irides. We also studied the
      pharmacology of prejunctional histamine receptors that regulate the release of
      norepinephrine (NE) from this tissue. The effect of exogenous histamine and
      various histamine receptor agonists was examined on the release of [(3)H]
      norepinephrine ([(3)H]NE) triggered by electrical field stimulation using the
      Superfusion Method. Histamine receptor agonists caused a concentration-dependent
      inhibition of field-stimulated [(3)H]NE overflow with the following rank order of
      potency: imetit > histamine > R-alpha-methylhistamine. In all cases, the
      inhibitory action of histamine receptor agonists was attenuated at high
      concentrations of these compounds. The histamine receptor antagonists,
      clobenpropit (H(3)-antagonist/H(4)-agonist) and thioperamide (H(3)-antagonist)
      blocked the inhibitory response elicited by R-alpha-methylhistamine and imetit,
      respectively. Inhibitory effects of R-alpha-methylhistamine and clonidine were
      not additive suggesting that prejunctional H(3)- and alpha(2)-adrenoceptors
      coexist at neurotransmitter release sites. We conclude that histamine produces an
      inhibitory action on sympathetic neurotransmission in the bovine iris, an effect
      mimicked by selective H(3)-receptor agonists and blocked by H(3)-antagonists.

PMID- 16804759
TI  - Intranigral dopamine toxicity and alpha-synuclein response in rats.
AB  - There is increasing evidence that, in addition to its function as the main
      neurotransmitter in the nigrostriatal pathway, dopamine (DA) may be neurotoxic in
      certain conditions. In this study, the toxicity of DA was assessed by direct
      injection into the substantia nigra of anaesthetised rats, and its effects were
      compared with those of 6-hydroxydopamine. Brains were removed 1, 2 and 3 weeks
      after the lesion for histological or neurochemical analysis. DA caused a
      significant loss of 35% of tyrosine hydroxylase-positive neurons in the pars
      compacta of substantia nigra and a 40% reduction of striatal DA content. Cells
      with signs compatible with both apoptosis and autophagy were observed. GADD153, a
      parameter of endoplasmic reticulum stress, was strongly induced by 6
      hydroxydopamine but not by DA. DA increased the alpha-synuclein content 1 week
      after the lesion (but not at the later times analyzed) in tyrosine hydroxylase
      positive and in non-dopaminergic fibers of pars reticulata. The alpha-synuclein
      increase may be a physiological temporal response to DA accumulation and/or to
      cell damage, but the simultaneous presence of alpha-synuclein and DA in the cell
      cytoplasm at concentration higher than normal is not exempt from risk. In fact,
      their incubation in a free cell system gives a stable dimerized form of alpha
      synuclein that has been described as the critical rate-limiting step for its
      abnormal fibrillation.

PMID- 16804760
TI  - Differential involvement of intracellular Ca2+ in 1-methyl-4-phenylpyridinium- or
      6-hydroxydopamine-induced cell viability loss in PC12 cells.
AB  - 1-Methyl-4-phenylpyridinium (MPP(+)) or 6-hydroxydopamine (6-OHDA) caused a
      nuclear damage, the mitochondrial membrane permeability changes, leading to the
      cytochrome c release and caspase-3 activation, the formation of reactive oxygen
      species and the depletion of GSH in PC12 cells. Nicardipine (a calcium channel
      blocker), EGTA (an extracellular calcium chelator), BAPTA-AM (a cell permeable
      calcium chelator) and calmodulin antagonists (W-7 and calmidazolium) attenuated
      the MPP(+)-induced mitochondrial damage and cell death. In contrast, the
      compounds did not reduce the toxicity of 6-OHDA. Treatment with MPP(+ )or 6-OHDA
      evoked the elevation of intracellular Ca(2+) levels. Unlike cell injury, addition
      of nicardipine, BAPTA-AM and calmodulin antagonists prevented the elevation of
      intracellular Ca(2+) levels due to both toxins. The results show that the MPP(+)
      induced formation of the mitochondrial permeability transition seems to be
      mediated by elevation of intracellular Ca(2+) levels and calmodulin action. In
      contrast, the 6-OHDA-induced cell death seems to be mediated by Ca(2+)
      independent manner.

PMID- 16804761
TI  - Treatment and prophylaxis of anthrax by new neurosecretory cytokines.
AB  - In 1881, Louis Pasteur described the Bacillus anthracis vaccine, which plays an
      important role for the treatment and prophylaxis of anthrax. Currently, treatment
      for anthrax infection involves the use of several different antibiotics, used in
      combination with vaccines, which possess potential virulence in white mice and
      guinea pigs. We discovered several new immunomodulators cytokines (polypeptides)
      produced by the neurosecretory cells of hypothalamus, some of which can be used
      as drugs for the treatment and prophylaxis of the anthrax. The proline-rich
      polypeptides, which consist from 10 to 15 amino acids and four proline residues,
      are of the special interest; one of them (PRP-1), which consist of 15 amino acids
      and has the following primary structure ALa-GLy-ALa-Pro-GLu-Pro-Ala-GLu-Pro-Ala
      GLn-Pro-GLy-Val-Tyr (AGAPEPAEPAQPGVY) possesses antibacterial activity, and a new
      proline-rich peptide described by Galoyan and called Gx-NH2. Both were tested for
      treatment against the anthrax bacillus or anthrax strain N55 vaccine in guinea
      pigs and mice in vivo, and in vitro preparations. The results of experiments show
      that these hypothalamic neurosecretory cytokines have a strong prophylaxis and
      therapeutic properties towards animals infected by episodic strain of anthrax and
      anthrax vaccine N55. The conventional concepts concerning the function of
      hypothalamic neurosecretion and hypothalamic mechanisms of adaptation have to be
      reconsidered.

PMID- 16804762
TI  - Information content of fluorescence polarization and anisotropy.
AB  - The equality of information content in fluorescence polarization and emission
      anisotropy is a common assumption and the two quantities are used according to
      practical considerations. However, an information-theoretic analysis presented
      here reveals that their information content is substantially different. A scaling
      relation exists between polarization and anisotropy, and normalization allows
      their direct comparison. Various measures of information such as the absolute,
      relative, differential, and potential entropies all appear larger for anisotropy
      over part or all of its normalized overlap with the polarization function. The
      larger information content coincides with the signal range where the emitted
      light is polarized mostly in the parallel direction. Polarization takes on larger
      absolute entropy only when the emission is about perpendicular to the incident
      light and when the differential entropy is considered over the entire physical
      domain. The additional information locally afforded by polarization appears to be
      related to its larger signal range whereas the extra information in anisotropy
      may be attributed to a second perpendicular emission plane in its definition,
      which is oriented along the axis of propagation of light and takes the
      contribution of all degrees of rotational freedom into account. Thus anisotropy
      may be considered as a more accurate and more informative representation of the
      underlying physical phenomena. Some practical aspects relevant to studies of
      protein-ligand interactions are also discussed.

PMID- 16804763
TI  - 25-year trends and socio-demographic differences in response rates: Finnish adult
      health behaviour survey.
AB  - When estimating population level changes in health indicators, the declining
      response rate, especially if also the characteristics of non-respondents are
      changing may bias the outcome. There is evidence that survey response rates are
      declining in many countries. It is also known that respondents and non
      respondents differ in their socio-economic and demographic status as well as in
      their health and health behaviours. There is no information about the changes in
      the differences between respondents and non-respondents over time. Our purpose
      was to investigate the changes over time in the differences between respondents
      and non-respondents in respect to their sex, age, marital status and educational
      level. The data from the Finnish Adult Health Behaviour Survey (1978-2002) was
      used. The response rate declined over the past 25 years for both men and women in
      all age groups. The decline was faster among men than women, and also faster in
      younger age groups than older age groups. There is a marked difference in the
      response rate between married and non-married persons but it did not change over
      time. Also the response rate between different educational levels differed for
      both men and women, and this difference increased over the years. The declining
      response rate and at the same time occurring change in the non-respondent
      characteristics will decrease the representativeness of the results, limit the
      comparability of the results with other surveys, increase the bias of the trend
      estimates and limit the comparability of the results between population groups.

PMID- 16804764
TI  - Protective immunity in rats by intranasal immunization with Streptococcus mutans
      glucan-binding protein D encapsulated into chitosan-coated poly(lactic-co
      glycolic acid) microspheres.
AB  - Recombinant Streptococcus mutans glucan-binding protein D (rGbpD) was
      incorporated into poly(lactic-co-glycolic acid) (PLGA) microspheres which then
      were surface-coated with chitosan. The microspheres, with a mean diameter of ca.
      1.8 microm, were intranasally administered in rats. There were elevated salivary
      immunoglobulin A and serum immunoglobulin G antibody responses to rGbpD, as well
      as lower molar caries scores in immunized animals as compared to sham immunized
      ones. The chitosan-coated PLGA microspheres are thus potentially useful for
      antigen delivery in dental caries vaccination.

PMID- 16804766
TI  - Resonance assignments of the 34 kD rabbitpox vCCI:human MIP-1beta complex.

PMID- 16804765
TI  - Delivery of antibody-captured proteins into living cells using PTD-fused protein
      A.
AB  - Protein transduction domain (PTD)-mediated protein delivery into animal cells is
      a useful technique for regulating cellular functions. Proteins captured by
      antibodies were delivered into living cells using an antibody/PTD-fused protein A
      complex. As a model protein, fluorescent-modified antibodies, captured by their
      respective primary antibody, were analyzed by fluorescence-activated cell sorting
      (FACS) which showed that the fluorescent-modified antibodies were directly
      delivered into cells. Peroxidase, captured by its specific antibody, was also
      delivered into cells and retained its activity.

PMID- 16804767
TI  - 1H, 13C, and 15N chemical shift assignments of neuronal calcium sensor-1, a multi
      functional calcium-binding protein.

PMID- 16804768
TI  - Immigration of phytoseiid mites from surrounding uncultivated areas into a newly
      planted vineyard.
AB  - This study reports (1) a faunistic survey of phytoseiid mites observed inside a
      vine plot and in neighbouring vegetation (other vine plots and uncultivated
      areas) and (2) dispersal of phytoseiid mites into the plot studied. These data
      aim to raise some hypotheses concerning natural colonisation of a vineyard by
      predatory mites. The study was carried out over 3 years (1999, 2000 and 2001) in
      an experimental plot planted with two cultivars (Grenache and Syrah) and with
      Sorbus domestica in a framework of agroforestry investigations. Phytoseiid mites
      were collected in both cultivated and uncultivated areas surrounding the
      experimental plot, and their dispersal into the plot studied using "aerial"
      traps. Densities remained quite low compared to previous studies. The main
      species encountered in the uncultivated areas and in the traps was Typhlodromus
      phialatus. Despite the low numbers of phytoseiid mites trapped, densities of
      phytoseiid mites into the vine field increased during 3 years. Typhlodromus
      phialatus, the species mainly found in the neighbouring uncultivated areas, was
      rarely found in vineyards. Another morphologically close species was predominant
      on vines: Typhlodromus exhilaratus. However, Kampimodromus aberrans the main
      phytoseiid mite species in vineyards of Southern France was not found in the
      present survey. Hypotheses for this colonisation process are discussed.

PMID- 16804769
TI  - Spatial distribution of mites of the suborder Uropodina (Acari: Mesostigmata) in
      a small isolated forest area.

PMID- 16804770
TI  - Effects of a sigh on the respiratory mechanical properties in ali patients.
AB  - OBJECTIVES: The application of sighs during baseline ventilation was found to
      improve alveolar recruitment and oxygenation in patients with acute respiratory
      distress syndrome (ARDS). The present investigation evaluates if respiratory
      mechanics can be modified by a sigh. METHODS: Ten consecutive patients with acute
      lung injury (ALI) admitted to the University Hospital Intensive Care Unit the
      were studied during mechanical ventilation. Three sighs were administered to
      sedated-paralyzed patients during the measurement period. Respiratory mechanics
      were studied in regular breaths immediately before and after a sigh provided that
      a steady-state had been reached and by the airway pressure-time curve profile to
      evaluate the lung recruitment. Viscoelastic constants (elastic, resistive, and
      time), as well as elastance and resistances, were determined by the single breath
      method. Arterial blood gases were also determined pre- and post-sigh. RESULTS:
      Elastic and resistive components of viscoelasticity decreased after a sigh (20
      and 21%, respectively). As a result, the pressure required to overcome
      viscoelasticity and mechanical inhomogeneities also decreased in these patients
      (17%). The mechanical changes were associated with alterations in PaO(2).
      CONCLUSIONS: The sigh is useful to diminish viscoelastic impedance in ALI
      patients, thus allowing a smaller inflation pressure. Under the present
      experimental conditions it seems that viscoelastic mechanical alterations precede
      their elastic and resistive counterparts.

PMID- 16804771
TI  - [Usefulness of imaging devices in glaucoma].

PMID- 16804772
TI  - Corneal vascularisation and contact lenses.

PMID- 16804773
TI  - [Lacrimal intubation in complicated cases].

PMID- 16804774
TI  - [Corneal macular dystrophy: clinical, histopathologic and ultrastructural
      features].
AB  - OBJECTIVE: To assess the main clinical, genetic, histopathological and
      ultrastructural features of Mexican patients with macular corneal dystrophy, and
      to compare the results with those previously reported. METHOD: We analyzed six
      cases where a histopathologic diagnosis of macular corneal dystrophy had been
      made between 1957 and 2004. RESULTS: Clinically, all corneas showed focal grayish
      white stromal opacities with diffuse edges. Histopathologically, intrastromal
      granules stained strongly positive with Alcian blue and colloidal iron.
      Transmission electron microscopy showed enlargement of smooth endoplasmic
      reticulum and the presence of intracytoplasmic vacuoles that corresponded to
      glycosaminoglycans. Genetic analysis showed novel mutations in the CHST6 gene in
      2 of the patients. CONCLUSIONS: Females were more affected than males and the
      mean age at the time of diagnosis was older than that reported previously,
      however the clinical, histopathological and ultrastructural features were similar
      to those of previous reports. As described in other cases in the literature, in
      some instances a disorder is found in CHST6 gene as a basis for this condition.

PMID- 16804775
TI  - [Macular hole surgery without postoperatory <<face>> down positioning. Pilot
      study].
AB  - PURPOSE: To evaluate the visual and anatomical outcomes of macular hole surgery
      using phacoemulsification, vitrectomy and intraocular gas tamponade without the
      use of postoperative face down positioning. METHODS: Phacoemulsification with an
      intraocular lens implant, followed by vitrectomy with internal limiting membrane
      peeling and perfluoropropane (C3F8), was performed in patients with stage 3 or 4
      macular holes. After surgery, patients had to avoid the supine position for 15
      days. Patients with a gas level <50% during the first week had a fluid-gas
      exchange. Visual acuity and closure of the macular hole were evaluated after 1
      year of follow-up. RESULTS: 20 eyes of 20 patients, aged 60 to 75 years (median
      age 68 years), were included in this study. The best initial visual acuity ranged
      from 0.05 to 0.13 (ETDRS), with the median being 0.06. The final visual acuity
      was 0.05 to 0.30 with a median of 0.10. A statistically significant improvement
      (p=0.001, Wilcoxon) was found. The anatomic postoperative results revealed 90%
      (n=18) of the macular holes were closed while 10% (n=2) were not. CONCLUSIONS:
      Macular hole surgery has, in general, good results and patients can achieve
      improvement in their visual acuity without the need for uncomfortable and
      unbearable post operative posture positions.

PMID- 16804776
TI  - [Reduction of corneal permeability in patients treated with HP-guar: a
      fluorophotometric study].
AB  - INTRODUCTION: The incidence of dry eye disease, which mainly affects the corneal
      epithelium, is rising. The main treatment is still the use of artificial tears
      capable of improving the humidification and lubrication of the corneal
      epithelium, and avoiding its progressive functional failure. HP-Guar is a new
      compound used for this purpose. METHODS: We performed a prospective, masked and
      paired study on the left eye of 10 patients suffering from dry eye disease.
      Corneal permeability measurements were performed by fluorophotometry after
      instilling 40 microL of a solution of 2% sodium fluorescein, before and after
      treatment with the HP-Guar drops. The results were analysed using Wilcoxon test
      for paired data. RESULTS: A mean decrease in corneal permeability of 45%, after
      the use of HP-Guar drops was found (p=0.002). CONCLUSIONS: HP-Guar provides a new
      therapeutic option significantly decreasing corneal epithelial permeability.

PMID- 16804778
TI  - [Juxtapapillary capillary hemangioma and central serous retinopathy: description
      of a case with spontaneous resolution].
AB  - CASE REPORT: A patient presented with a unilateral decrease of visual acuity and
      was found to have a juxtapapillary capillary hemangioma by ophthalmoscopy
      (confirmed by fluorescein angiography) and atrophy in the retinal pigmentary
      epithelium with leakage points suggesting bilateral central serous retinopathy.
      Spontaneous resolution of the hemangioma, as well as the central serous
      retinopathy, subsequently occurred. DISCUSSION: The decrease of visual acuity in
      a patient with a juxtapapillary capillary hemangioma has been associated with
      complications from the lesion itself, but an association of central serous
      retinopathy, as a possible predisposing factor, has not been previously
      described.

PMID- 16804777
TI  - [Choroidal effusion and retinal detachment after capsulotomy with YAG-LASER].
AB  - CASE REPORT: A 74-year-old woman presented complaining of blurred vision in her
      left eye. She had an anterior chamber lens in both eyes and an opaque posterior
      capsule in her left eye, for which a YAG-LASER capsulotomy was performed.
      Thirteen days later she re-presented with a choroidal effusion and a retinal
      detachment requiring surgery. DISCUSSION: There is no consensus as to the exact
      time at which a capsulotomy should be done. Timing of the procedure requires
      evaluation as a whole and consideration of the potential complications of IOL
      dislocation, recurrent uveitis, ocular hypertension and the most devastating
      choroidal effusion and retinal detachment.

PMID- 16804779
TI  - [Choroidectomy in choroidal melanocytoma. Clinical and histopathologic
      characteristics].
AB  - PURPOSE/METHODS: To report a rare case of melanocytoma in a choroidal location.
      The clinical and echographic characteristics were similar to those of a melanoma.
      The treatment selected in our case was a choroidectomy. Tissue was stained with
      hematoxylin-eosin, periodic acid-Schiff, Masson's trichromic and
      immunohistochemistry was performed. RESULTS/CONCLUSIONS: The clinical and
      histopathologic features of choroidal melanocytoma are similar to the
      characteristics of a melanocytoma located in other parts of the eye. The
      differential diagnosis between choroidal melanoma and melanocytoma is very
      difficult without histopathologic correlation.

PMID- 16804780
TI  - [Severe ocular side effects with Topamax].
AB  - CASE REPORTS: We describe 2 patients who developed ocular side effects during
      treatment with topiramate. One was a 16-year-old woman with generalized seizures
      who developed a homonymous hemianopia after using topiramate 125 mg per day for
      12 weeks, and the other was a 24-year-old epileptic female who developed a
      bilateral maculopathy after using topiramate 150 mg per day for 8 weeks.
      DISCUSSION: We identified two severe ocular adverse reactions from topiramate.
      Both reactions necessitated discontinuing the treatment, but the topiramate
      associated maculopathy was irreversible.

PMID- 16804781
TI  - [Weill-Marchesani's syndrome: familial involvement].
AB  - CASE REPORT: We report the case of a child short in stature with brachydactyly
      and brachymorphy who was referred to our office complaining of poor vision. This
      was a case of Weill-Marchesani's syndrome described in a family, in which four of
      the eight children were affected by spherophakia, brachymorphy and brachydactyly.
      DISCUSSION: There are few familial cases of Weill-Marchesani's syndrome reported
      in the literature. Both autosomal dominant and recessive inheritances have been
      described. The opththalmologist plays a crucial role in its diagnosis and
      management, since the ocular involvement is the most severe one.

PMID- 16804782
TI  - [Ophthalmic remedies in the Materia Medica of Dioscorides (III)].

PMID- 16804783
TI  - [The laser].

PMID- 16804784
TI  - [The influence of intraoperative fluid therapy on the postoperative outcome in
      "fast track" colon surgery].
AB  - OBJECTIVE: To evaluate the association between the intraoperative and
      postoperative application of different quantities of fluids and the incidence of
      postoperative complications after "fast-track"-colonic surgery. METHODS: We
      performed a retrospective analysis of 136 patients undergoing elective "fast
      track" colonic surgery (sigma resection and right hemicolectomy). Data collection
      in regard of fluid administration during surgery and in the post anaesthesia care
      unit (PACU) was based on anaesthesia charts and a prospectively generated surgery
      database. Classification into three volume groups (up to 3500 ml = group 1, 3500 
      5500 ml = group 2, more than 5500 ml = group 3). Basic patient characteristics,
      pre-existing conditions, type and duration of surgery and anastomoses were
      documented. We analysed the incidence of postoperative complications such as
      wound infections, anastomotic leak, bleeding, bowel obstruction, cardiovascular
      failure, hypertension, pulmonary failure, pneumonia, renal failure, urinary tract
      infection, neurological and psychiatric complications in the different volume
      groups. RESULTS: 115 patients were infused with up to 3500 mLs of fluids, 19
      patients received more than 3500 mLs, two patients were infused with 6000 ml and
      7500 mLs, respectively. This was in median 36 ml/kg in the restrictive and 53
      ml/kg in the higher volume groups (group 2 and 3 together), respectively. The
      duration of surgery and anaesthesia was significantly different between both
      fluid groups (p = 0,023). In a logistic regression model only intraoperative
      blood loss was independently associated with the volume of infused fluid (OR
      0,393, 95 % CI 1.028 - 2.306, p < 0.01). The rate of postoperative complications
      was not different between groups (p = 0,228). CONCLUSION: The incidence of
      postoperative complications was not different between patients who were infused
      36 ml/kg or 53 ml/kg of fluids during surgery and post anaesthesia care unit
      stay.

PMID- 16804786
TI  - [Emergency management--simultaneous management of large numbers of injured or ill
      patients].

PMID- 16804787
TI  - [Pharmacotherapy: argatroban--alternative to heparin in case of heparin-induced
      thrombocytopenia type II (HIT II)].

PMID- 16804788
TI  - [Phantom limb pain].
AB  - Almost everyone who has amputated a limb will experience a phantom limb. They
      have the vivid impression, that the limb is still present. 60 to 70% of these
      amputees will suffer from phantom limb pain. The present paper gives an overview
      of the incidence and the characteristics of the so called "post amputation
      syndrome". Possible mechanism of this phenomena are presented, including
      peripheral, spinal, and central theories. Treatment of phantom limb pain is
      sometimes very difficult. It includes drug therapy, psychological therapy,
      physiotherapy as well as the prevention of phantom limb pain with regional
      analgesia techniques.

PMID- 16804789
TI  - [Fluid therapy--introduction].

PMID- 16804790
TI  - [Fluid therapy--pathophysiological principles as well as intra- and perioperative
      monitoring].

PMID- 16804791
TI  - [Fluid therapy--volume therapy in fast-track colon surgery].

PMID- 16804792
TI  - [Fluid therapy--volume therapy in vascular surgery for the example of the
      abdominal aorta].

PMID- 16804793
TI  - [Fluid therapy--preclinical volume therapy in the management of polytrauma].

PMID- 16804794
TI  - Hypercalcitoninemia in a patient with a recurrent goitre and insulinoma: a case
      report.
AB  - Serum calcitonin has become a very sensitive and specific marker for medullary
      thyroid carcinoma that should be determined in patients with nodular thyroid
      disease. However, a few earlier reports indicated that tumors other than
      medullary thyroid carcinoma including insulinomas arising from pancreatic islet
      cells may also produce calcitonin. Of the few cases of calcitonin-producing
      insulinomas previously reported, most had incomplete data or lack of
      documentation of the association between raised serum calcitonin concentration
      and immunohistochemical detection of calcitonin in pancreatic islet cell tumors.
      In this paper we are reporting a 54-year-old woman with a history of partial
      thyroidectomy for multinodular goitre at the age of 50 yrs, she was evaluated for
      a 2-months history of fasting hypoglycemia (plasma glucose 1.9 mmol/L during a
      supervised fast), raised serum insulin (at the time of hypoglycemia 88.8
      microU/ml; normal, 5 - 35 microU/ml) and C-peptide levels (at the time of
      hypoglycemia 6.1 ng/ml; normal, 1.37 - 3.51 ng/ml), markedly increased serum
      calcitonin concentration (481 pg/ml; normal, < 9.9 pg/ml), and an enlarged
      residual thyroid gland. Aspiration biopsy of the thyroid was negative for
      parafollicular C-cell hyperplasia or medullary thyroid carcinoma. Abdominal
      ultrasound and CT scan revealed a tumor in the head of the pancreas, which was
      surgically removed. Histopathological evaluation of the pancreatic tumor showed
      typical features of a neuroendocrine neoplasm with strong immunostaining for both
      insulin and calcitonin. After removal of the pancreatic tumor, clinical symptoms
      resolved and biochemical markers normalized (serum insulin, 14.9 microU/ml; C
      peptide, 3.0 ng/ml; calcitonin, 2.9 pg/ml) confirming the causal relationship
      between insulinoma and markedly increased serum calcitonin levels.

PMID- 16804795
TI  - Influence of short-term interruption of antithyroid drugs on the outcome of
      radioiodine therapy of Graves' disease: results of a prospective study.
AB  - AIM: The factors influencing success of treating Graves' disease with radioiodine
      ( (131)I) are discussed controversially. This study analyses prospectively the
      influence of discontinuing antithyroid drugs (ATD) immediately prior to treatment
      with radioiodine on the therapeutic outcome. METHODS: We studied 141 patients
      with Graves' disease. In 73 of them (group A) treatment was performed under
      medication with ATD, in 68 patients (group B) ATD were discontinued for 3 - 7
      days starting at the time of therapy. We performed a statistical analysis of the
      influence of ATD and other factors potentially influencing treatment results.
      RESULTS: In group A 49/73 patients were treated successfully (67 %) vs. 58/68 (85
      %) in group B (p < 0.01). Characteristic changes in the kinetics of radioiodine
      were observed: after discontinuing ATD specific uptake was higher (2.0 %/ml in
      group A vs. 2.6 %/ml in group B, p = 0.004), and the effective half life was
      longer (5.1 +/- 1.3 d in group A vs. 5.5 +/- 1.1 d in group B, p = 0.076)
      resulting in a significantly higher radiation dose in group B (200 +/- 61 Gy in
      group A vs. 236 +/- 72 Gy in group B, p = 0.002). CONCLUSION: We conclude that
      short-term interruption of ATD improves the success rate of treating Graves'
      disease with radioiodine significantly.

PMID- 16804796
TI  - Initially elevated TSH and congenital central hypothyroidism due to a homozygous
      mutation of the TSH beta subunit gene: case report and review of the literature.
AB  - Congenital central hypothyroidism (CCH) is a rare disease which can be caused by
      mutations in the gene for the thyrotropin (TSH) beta subunit ( TSHB). The
      diagnosis is usually delayed because the TSH serum levels in these patients are
      not elevated leading to a negative result in the neonatal TSH screening. Herein,
      we report a 2-year-old girl with CCH due to a mutation in the TSHB gene, in whom
      the unusual finding of an initially elevated TSH level complicated the diagnostic
      workup. The proposita, who had a supposedly normal TSH screening result, is a
      German girl of non-consanguineous parents. At 5 weeks of age, her thyroid
      function tests showed peripheral hypothyroidism with a moderately increased TSH
      (23.8 microIU/ml) so that thyroid hormone substitution was initiated. At the age
      of 2 years, the administration of TRH failed to increase the TSH serum
      concentrations, which prompted TSH measurements with two different assay systems.
      Variable TSH levels ranging from not detectable low to elevated were found so
      that central hypothyroidism due to a mutation in the TSHB gene was suspected.
      This was confirmed by molecular analysis of the TSHB gene, which identified a
      homozygous deletion (delta 313 T) in the coding sequence. This mutation has been
      found in the German population before and may be a founder mutation. We conclude
      that depending on the assay system variable TSH serum levels in individuals with
      mutations in the TSHB gene may complicate the diagnostic workup.

PMID- 16804797
TI  - Incidence of radioiodine induced Graves' disease in patients with multinodular
      toxic goiter.
AB  - In this study, we assessed the incidence of Graves' disease (GD) following
      radioiodine therapy (RIT) in a large cohort of well characterized patients with
      autonomy in comparison to the clinical course of control patients with thyroidal
      autonomy not definitively treated with (131)I or surgery. 622 consecutive
      patients were treated with (131)I for autonomy (unifocal: n = 321; multifocal: n
      = 199; disseminated: n = 102) and followed up for at least 6 months post RIT. 108
      consecutive patients with autonomy not definitively treated (unifocal: n = 49;
      multifocal: n = 42; disseminated: n = 11) followed up for at least 6 months
      served as controls. Initial evaluation and follow-up included determination of
      FT3, FT4, TSH, autoantibodies against the thyroid peroxidase (anti-TPO) and TSH
      receptor antibodies (TRAb) by highly sensitive radio receptor-assay, quantitative
      thyroid scintigraphy and sonography. After 6 months, GD was newly diagnosed in
      1/321 patients with unifocal autonomy, in 1/199 patients with multifocal autonomy
      and in 0/108 control patients. In patients with disseminated autonomy (group C),
      GD was diagnosed significantly more often compared to the other groups (5/102
      patients; 4,1 %; p < 0.05). In conclusion, RIT may induce Graves' disease in a
      few cases with toxic multinodular goiter. The incidence in this population is
      small. Compared with patients suffering from uni- or multifocal autonomy,
      subjects with disseminated autonomy have a more than tenfold higher risk for the
      development of GD.

PMID- 16804798
TI  - Knowledge about diabetes and participation in diabetes training courses: the need
      for improving health care for diabetes patients with low SES.
AB  - The association between socioeconomic status (SES) and health is well known, and
      many determinants of these health inequalities have been studied. Concerning the
      role of health care, the results are conflicting, though. The study adds to this
      discussion by focussing on health care differences for people with type 2
      diabetes. The analyses are based on a study conducted in Southern Germany (WHO
      MONICA study, Augsburg myocardial infarction registry). The sample consists of
      378 type 2 diabetic patients, divided into two clearly distinct groups: one group
      (n = 210) from a MI registry with clinically confirmed myocardial infarction
      (MI), the other (n = 168) from a population based survey, characterised by the
      absence of a previous MI. Ten topics are differentiated in the assessment of
      diabetes knowledge (diet, weight control, etc.). The analyses show that knowledge
      about diabetes increases with increasing educational level. Concerning "very well
      informed about diet", for example, the odds ratio for the high educational group
      is 3.45 (95 % CI: 1.34 - 8.86) as compared with the low educational group. This
      association is restricted to those diabetic persons with previous MI. For diet,
      the odds ratio for this subsample increases to 7.35 (p < 0.05). Similar results
      are seen for the other topics of diabetes knowledge. Also, diabetic persons with
      a low educational level participated in diabetes training courses least often,
      especially in the subsample with previous MI. Thus, taking the example of type 2
      diabetes, the study adds to the evidence that the inverse care law is still
      present today in Germany.

PMID- 16804799
TI  - Insulin sensitivity indices: a proposal of cut-off points for simple
      identification of insulin-resistant subjects.
AB  - Demanding measurement of insulin sensitivity using clamp methods does not
      simplify the identification of insulin resistant subjects in the general
      population. Other approaches such as fasting- or oral glucose tolerance test
      derived insulin sensitivity indices were proposed and validated with the
      euglycemic clamp. Nevertheless, a lack of reference values for these indices
      prevents their wider use in epidemiological studies and clinical practice. The
      aim of our study was therefore to define the cut-off points of insulin resistance
      indices as well as the ranges of the most frequently obtained values for selected
      indices. A standard 75 g oral glucose tolerance test was carried out in 1156
      subjects from a Caucasian rural population with no previous evidence of diabetes
      or other dysglycemias. Insulin resistance/sensitivity indices (HOMA-IR, HOMA-IR2,
      ISI Cederholm, and ISI Matsuda) were calculated. The 75th percentile value as the
      cut-off point to define IR corresponded with a HOMA-IR of 2.29, a HOMA-IR2 of
      1.21, a 25th percentile for ISI Cederholm, and ISI Matsuda of 57 and 5.0,
      respectively. For the first time, the cut-off points for selected indices and
      their most frequently obtained values were established for groups of subjects as
      defined by glucose homeostasis and BMI. Thus, insulin-resistant subjects can be
      identified using this simple approach.

PMID- 16804800
TI  - Diabetes mellitus is no independent risk factor for perioperative mortality
      following hepatic resection.
AB  - For patients with concomitant diabetes mellitus an increased perioperative
      mortality and morbidity in hepatic resections has repeatedly been described.
      Other studies, however, demonstrated equal outcome data in diabetic and non
      diabetic patients. As patient populations were selected for underlying disease,
      conflicting results may reflect patient selection criteria rather than impact of
      diabetes mellitus on outcome measures. Therefore, a multivariate analysis in a
      largely unselected patient population has been performed to determine the
      independent prognostic value of diabetes mellitus in liver surgery. From a
      prospective database 633 adult patients undergoing hepatic resection without
      preceding major abdominal surgery or chemotherapy have been identified. Besides
      diabetes mellitus, demographic data, variables expressing the functional reserve
      of the liver, and parameters of surgical technique were analyzed for their impact
      on mortality and morbidity. 75 patients were diabetic (11.8 %) and 96 hepatic
      resections (15.2 %) were performed in cirrhotic patients. In the univariate
      analysis, concomitant diabetes was associated with an increased mortality
      compared to all non-diabetic patients (10.7 % vs. 5.3 %, p = 0.047). Diabetic
      patients, however, were also significantly older and presented a higher
      prevalence of liver cirrhosis. Multivariate modeling finally identified only age,
      albumin, cirrhosis, extent of surgery, and era of surgery as independent
      variables with an impact on perioperative mortality. Overall, complications were
      detected in diabetic and non-diabetic patients with a comparable frequency (44 %
      vs. 36 %, p = 0.179). Also, the length of in-hospital stay did not significantly
      differ between both groups (18.5 +/- 1.7 vs. 17.7 +/- 1.0 days, p = 0.119). Rates
      of postoperative renal impairment, prolonged ascites or pneumonia, however, were
      higher in diabetics than in other patients. Following established cardiopulmonary
      and surgical selection criteria, diabetes mellitus is not an independent risk
      factor for perioperative mortality in hepatic resections. Although the overall
      postoperative morbidity was not different in diabetic and non-diabetic patients,
      a specific pattern of complications has been identified, mandating particular
      attention in the postoperative course of diabetic patients.

PMID- 16804801
TI  - Did the gradual loss of GLUT2 cause a shift to diabetic disorders in the New
      Zealand obese mouse (NZO/Hl)?
AB  - The New Zealand obese mouse (NZO/Hl) is characterised by hereditary obesity and
      type-2 diabetes, including insulin resistance, hyperinsulinaemia, and glucose
      intolerance. In other diabetic models, it has been revealed that the proper
      functioning of the glucose transporter isoform 2 (GLUT2) is essential for
      adequate secretion of insulin. The aim of this study was to compare the
      distribution of islet cells and GLUT2, as well as the expression of GLUT2-mRNA,
      in the pancreas of NZO mice and metabolically unimpaired NMRI (Naval Medical
      Research Institute) mice. Pancreas tissue was obtained from different stages of
      development. For molecular determination of the expression level of GLUT2-mRNA,
      total-RNA was extracted from the pancreas and analysed by quantitative real-time
      RT-PCR. All investigated NZO mice displayed increased weight, elevated
      hyperinsulinaemia, and slightly enhanced blood glucose levels compared with the
      NMRI control mice. By means of immunofluorescence microscopy drastically reduced
      insulin levels were detected, which might be compensated by the observed islet
      cell hyperplasia and hypertrophy. Furthermore, the normally peripheral
      localisation of the alpha-cells within islets was disturbed. By contrast, there
      were no changes in somatostatin cell distribution. However, considerable
      differences appeared with regard to GLUT2: whereas the beta-cells of NMRI mice
      showed dense immunostaining of the GLUT2 transporter on the cell surface, in all
      age groups of NZO mice, GLUT2 on the plasma membranes was reduced and dispersed
      in the cytoplasm. These findings agree with the molecular biological results,
      which displayed decreased mRNA-expression of GLUT2. In summary, the observed
      alteration of islet morphology and of GLUT2 expression in diabetic mice
      complements our previous results from a superfusion protocol and further
      clarifies the mechanisms of diabetogenesis in NZO mice.

PMID- 16804802
TI  - Effect of physical fitness and endurance exercise on indirect biomarkers of
      recombinant erythropoietin misuse.
AB  - Erythropoietin (EPO) and soluble transferrin receptor (sTfR) in serum have been
      proposed as indirect biomarkers for the detection of recombinant human EPO
      (rhEPO) misuse in sport. The purpose of the present study was to investigate the
      influence of different levels of physical fitness, sport, different training
      workload during the sport season, and endurance exercise in the concentrations of
      these serum biomarkers for their application into mathematical models to
      indirectly detect rhEPO misuse. Serum EPO and sTfR concentrations were measured
      in 96 elite athletes of various sports along the sport season, in 21 recreational
      athletes at baseline (non exercising) conditions and in 129 other recreational
      athletes before and after long-distance races (10 and 21 km). In elite athletes,
      hemoglobin concentrations and percentage of reticulocytes were also measured, and
      indirect detection models applied. In recreational athletes, for EPO and sTfR,
      significant differences were only observed after the 21-km race. In baseline
      conditions, no differences were observed between recreational and elite athletes
      for EPO and sTfR. In elite athletes, individual EPO and sTfR concentrations
      slightly changed over the sport season, with coefficients of variation (CV) of
      26.1 % and 9.0 %, respectively. Hemoglobin and reticulocytes were influenced by
      sport, but their individual variation over the sport season was not
      physiologically relevant (CV of 3.7 % and 21.3 %, respectively). When applying
      mathematical models for detection of rhEPO administration, only one elite athlete
      obtained an individual model score above the established thresholds. Physical
      fitness, sport and different training workload during the sport season had no
      substantial effect on serum EPO and sTfR concentrations, except in recreational
      athletes after a 21-km race. Variations observed in mathematical models to detect
      EPO administration were mainly due to fluctuation in hemoglobin concentrations,
      commonly observed in elite athletes.

PMID- 16804803
TI  - [Prophylactic mastectomy in women at high risk for breast and ovarian cancer:
      qualitative analysis of the decision making process and long-term satisfaction of
      two women carrying a BRCA1-mutation].
AB  - PURPOSE: Bilateral prophylactic mastectomy and oophorectomy are currently the
      most effective prevention options for female carriers of the BRCA1 or BRCA2 gene.
      However, especially the mastectomy procedure is very invasive and is chosen
      rarely among high risk women in Germany. Little is known about how women cope
      with this surgery and their long-term satisfaction. METHODS: Face-to-face
      interviews were conducted with two BRCA1 mutation carriers, who had undergone
      prophylactic mastectomy in their twenties 9 and 16 years ago. The process of
      decision making and long-term satisfaction were analysed using Mayring's
      qualitative content analysis. RESULTS: Both high risk women had a significant
      family history of breast and ovarian cancer. They were repeatedly confronted with
      uncontrollable courses of disease in their relatives who died of breast cancer
      between the age of 20 and 30 and left small children behind. Although both women
      experienced different decision making and peri- and post-operative complications,
      both were satisfied with the decision for prophylactic surgery and showed no
      regret. DISCUSSION: Deciding to obtain genetic testing pushed women towards
      further decision making concerning prophylactic surgery in case they carry a
      mutation. Information about carrier status reduced uncertainty even if the result
      was adverse. Both high risk women experienced a decrease in cancer related
      anxiety which may have heightened tolerance for quality of life related
      impairments. Implications for counseling are described.

PMID- 16804804
TI  - [Is a decompressive hemicraniectomy sensible in space occupation through stroke
      or head and brain trauma?].

PMID- 16804805
TI  - [Isolated pareses of the terminal branches of the facial nerve: clinical
      findings, etiology and differential diagnosis].
AB  - Clinical findings from 35 patients with isolated paralyses of distinct branches
      of the facial nerve are demonstrated. Presumably because of its position, the
      mandibular marginal ramus has most often been affected (n = 21) followed by
      buccal (n = 6) and temporal branches (n = 4). In two patients, the pattern of
      perioral muscular pareses was compatible with lesions of more than one branch.
      Causes for the facial nerve branch lesions were iatrogenic (n = 25), tumor (n =
      4), trauma (n = 2), inflammatory (n = 1), idiopathic (n = 1) and congenital (n =
      2). The impact of the clinical investigation to distinguish supranuclear lesions
      is emphasized.

PMID- 16804806
TI  - [Polypharmacy in the treatment of schizophrenia].
AB  - Current standards for the pharmacological treatment of schizophrenia favour
      antipsychotic monotherapy. Most atypical antipsychotics developed in recent years
      meet the statutory requirement of being at least as effective as Haloperidol.
      Nevertheless, pharmacoepidemiological data show an increase in polypharmacy. The
      importance of the studies is underlined by the fact that 40 - 50 % of
      schizophrenic inpatients and up to 90 % schizophrenic outpatients receive
      antipsychotic combination therapies. Treatment resistance, reduction of dose
      related side effects caused by antipsychotic monotherapy or the effect on
      concomitant symptoms of schizophrenia, such as comorbid depression, might justify
      combination therapy or augmentation strategies. Apart from the high costs,
      polypharmacy is associated with reduced patient compliance and an increased risk
      of undesired pharmacological effects. Since polypharmacy is increasingly common
      further educational measures in psychopharmacology should be getting more
      attention. Due to the very small number of controlled studies that exist at
      present this report will focus on case reports of the most frequent as well as
      some of the lesser prescribed combination therapies. Finally, conclusions will be
      discussed in relation to therapy recommendations.

PMID- 16804807
TI  - [Suicidality - suicide and suicide prevention].

PMID- 16804810
TI  - Infertility and the environment: the medical context.
AB  - Approximately 10 to 15% of the population experiences infertility. Although 85 to
      90% of couples or individuals who experience infertility have a diagnosis for
      their infertility, underlying causes of infertility rarely are found. Extensive
      literature reporting adverse effects of environmental contaminants on wildlife
      and laboratory animal reproductive tract development, and reproductive function
      and epidemiologic studies with humans, suggests that many environmental chemicals
      and heavy metals may contribute to infertility. This article introduces the
      medical context in which infertility patients are evaluated and lays the
      foundation for health care professional and patient conversations, and medical
      education regarding environmental contaminants and human reproductive health for
      the future.

PMID- 16804811
TI  - Environmental contaminants, fertility, and multioocytic follicles: a lesson from
      wildlife?
AB  - The overall contribution of environmental exposures to infertility is unknown,
      but a growing scientific database suggests that exposure to various environmental
      factors, both in utero and neonatally, could dramatically affect adult fertility.
      Studies of various contaminant-exposed wildlife populations suggest that multiple
      mechanisms contribute to changes in gonadal development, maturation of germ
      cells, fertilization, and pregnancy; specifically, the endocrine processes
      supporting these events. Although great debate and extensive research has
      occurred during the last decade surrounding fertility, fecundity, and semen
      quality, much less work has focused on environmental alterations in oocyte
      development and maturation. Exposure of the developing ovary to estrogens,
      whether of pharmaceutical (e.g., diethylstilbesterol) or environmental (e.g.,
      phytoestrogens, pesticides with estrogenic action) origin, can disrupt early
      oogenesis and folliculogenesis leading to a pathology termed the multioocytic
      follicle (polyovular follicle), which in rodents reduces fertilization and
      embryonic survival rates. The mechanism underlying this pathology is hypothesized
      to involve a disruption in the gonadotropin-estrogen-inhibin/activin signaling
      pathway. Given the conserved nature of vertebrate oogenesis and folliculogenesis,
      we suggest that perturbations of these phenomena in humans, caused by
      environmental contaminant exposure, could lead to altered fertility, as has been
      reported in wildlife and laboratory rodent models.

PMID- 16804812
TI  - Does our environment affect our fertility? Some examples to help reframe the
      question.
AB  - The burden of unwanted infertility appears to be increasing, but links to
      environmental causes have, until recently, been difficult to establish. A large
      body of data suggests that sperm counts have been declining in Europe and the
      United States, but interpretation of these statistical trends remains
      controversial, and the role of the environment uncertain. We were able to show
      that some currently used pesticides are significantly associated with reduced
      sperm concentration by linking pesticide concentration in men's urine to results
      of their semen analysis. In a follow-up study, we showed that prenatal phthalate
      exposure was linked to subtle differences in genital development of male
      offspring that could impact the child's future fertility. Researchers are
      increasingly able to measure levels of environmental chemicals in human samples,
      and are using these to identify agents that impair fertility. These methods,
      rather than trend analyses, may lead more directly--and more persuasively--to
      identifying the role of environment in human fertility.

PMID- 16804813
TI  - Environmental influences on female fecundity and fertility.
AB  - An increasing body of evidence suggests that environmental exposures are
      adversely influencing female fecundity and fertility. Endocrine-disrupting
      compounds (EDCs) are of particular concern, due to their ability to interfere
      with the body's hormonal milieu. An overview of the literature regarding the
      effect of EDCs on female fecundity and fertility end points such as puberty,
      menstruation, endometriosis, time to pregnancy, pregnancy loss, reproductive
      senescence, and secondary sex ratio is presented. Methodologic challenges in
      studying the effects EDCs on sensitive reproductive end points are discussed and
      include exposure to mixtures, the choice of biologic media in which to measure
      compounds, laboratory methods, and varying modeling techniques. Also reviewed are
      novel technologies for home-based biospecimen collection and testing that offer
      promise for field-based research aimed at addressing questions about
      environmental influences on female fecundity and fertility.

PMID- 16804814
TI  - The environment and male fertility: recent research on emerging chemicals and
      semen quality.
AB  - Scientific and public concern about the potential risk of environmental chemicals
      to male reproductive health has been heightened by reports of downward trends in
      semen quality, as well as increased rates of developmental urogenital tract
      anomalies and testicular cancer. Of particular concern is whether some
      contemporary-use environmental chemicals alter semen quality. Specific toxicants
      of interest include phthalates and pesticides, as well as polychlorinated
      biphenyls (PCBs). The human data on the relationship of semen quality with
      phthalate and pesticide exposure are limited and do not currently allow for a
      definitive conclusion on whether adult exposure, at background environmental
      levels, alters semen quality. However, the epidemiologic data support an inverse
      association of PCBs with reduced semen quality, specifically reduced sperm
      motility. The associations found were generally consistent across studies despite
      a range of PCB levels. In addition to the chemicals discussed, there are
      additional classes of chemicals that require further study on their relation with
      human semen quality.

PMID- 16804816
TI  - Vallombrosa consensus statement on environmental contaminants and human fertility
      compromise.

PMID- 16804815
TI  - Role of exposure to environmental chemicals in the developmental basis of
      reproductive disease and dysfunction.
AB  - There is a paradigm shift in science at present that indicates that the onset of
      many diseases, including reproductive diseases and dysfunctions, are already
      programmed in utero or in the early postnatal period. This new field is called
      the developmental basis of health and disease. Although focus has been on the
      role of in utero nutrition and its effects on subsequent adult-onset diseases, it
      is clear that exposure to environmental stressors/toxicants in utero or during
      early development can also increase susceptibility to disease later in life. The
      mechanism for this in utero and early developmental effect is thought to be
      altered epigenetic control of gene expression, which alters developmental
      programming and results in a tissue that may appear normal but is functionally
      compromised. Although this concept is still a hypothesis, this review addresses
      the current state of data relating to proving its importance and role in
      reproductive diseases. If the developmental basis of disease is shown to be true,
      then examination of the etiology of disease and prevention and intervention
      strategies will need to be modified to fit the new paradigm.

PMID- 16804817
TI  - [Fitting soft contact lenses].

PMID- 16804818
TI  - [Anti-infective drug therapy in ophthalmology--part 4: acanthamoeba keratitis].
AB  - An early diagnosis of an acanthamoeba keratitis can usually be made on the basis
      of the patient's history and slit-lamp examination. Further helpful diagnostic
      steps are confocal microscopy, microbiological, and histopathological
      examination. In the early stages topical application of antimicrobials (combined
      application of aminoglycosides, polyhexamethylene biguanide 0.02 %, propamidine
      isoethionate 0.1 %) is effective. In the late stages a penetrating keratoplasty
      is often necessary.

PMID- 16804819
TI  - [Keratoconus: epidemiology, risk factors and diagnosis].
AB  - Keratoconus is a bilateral, non-inflammatory and progredient corneal ectasia with
      an incidence of approximately 1 per 2,000 in the general population. Within the
      second decade of life the cornea develops a conical shape, due to thinning of the
      corneal stroma with subsequent irregular astigmatism and myopia leading to marked
      impairment of vision. The most common presentation of the keratoconus is as a
      sporadic disorder, but it has long been recognized that a significant minority of
      patients exhibit a family history as an autosomal dominant mode of inheritance.
      Most investigators suggest complete penetrance of predisposing factors with
      variable phenotypic expression. In some patients heterozygous mutations in the
      VSX1 gene are described as the underlying gene defect. An association with Down
      syndrome, monosomia X (Turner syndrome), Leber's congenital amaurosis, mitral
      valve prolaps, collagenosis, retinitis pigmentosa and Marfan syndrome is
      described. The role of corneal cells in the pathogenesis of keratoconus is
      supported by the published reports of recurrence of keratoconus in eyes after
      penetrating keratoplasty due to graft repopulation by the recipient cells.
      Placido-based computeed videokeratographic corneal curvature mapping systems,
      linked with pachymetry, are useful for identifying overt and subclinical cases of
      keratoconus. Different indices may quantify the clinical features of keratoconus
      and may improve the classification. We compared videokeratometric data (Fourier
      series harmonic analysis and wavefront analysis) in eyes with keratoconus to
      answer the question of which parameters are useful for early diagnosis of
      keratoconus.

PMID- 16804820
TI  - [High tech in the diagnosis of glaucoma].
AB  - Scanning laser tomography (HRT, HRT II), scanning laser polarimetry (GDx nerve
      fibre analyser, GDx VCC), retinal thickness analyser (RTA) and optical coherence
      tomography (OCT, stratus OCT) provide objective measurements of the optic disc
      and the retinal nerve fibre layer suitable for the follow-up of glaucoma
      patients. Their ability to diagnose early glaucomatous damage is still limited
      but promising technical advances in this field can be expected in the future. For
      the moment, clinical examination and fundus photography still remain the gold
      standard for the assessment of glaucomatous optic disc and retinal nerve fibre
      layer damage.

PMID- 16804821
TI  - [Reoperations after LASIK].
AB  - BACKGROUND: Repeat operations after refractive surgery have increased in
      frequency during the past 10 years. The spectrum of the indications for repeat
      LASIK may have changed. METHODS: All cases of repeat operations after refractive
      surgery performed between May 1, 2004 and April 30, 2005 at the Institute of
      Refractive and Ophthalmic Surgery (IROC) were retrospectively investigated
      regarding indication for repeat surgery and visual and refractive results. The 1
      month results were used to estimate the refractive and visual success rate.
      RESULTS: Of the 76 reoperations, 69 were performed as re-lifts, 3 eyes had new
      lamellae cut, and 3 cases needed keratoplasties. The reoperations took place 7.5
      +/- 13 months after the primary operation (range 0.5 to 60 months). The most
      frequent indication was residual astigmatism of 0.5 D and more. Visual loss of
      more than 1 decimal line did not occur and unaided visual acuity increased from
      0.64 to 1.05. No complications were reported, however, 3 eyes needed additional
      enhancement. CONCLUSIONS: Reoperations after LASIK performed as re-lifts appear
      to be effective and reasonably safe when using the technique described and
      respecting a residual stromal thickness of 280 microns.

PMID- 16804822
TI  - [Endoresection of large uveal melanomas after pretreatment by single-dose
      stereotactic convergence irradiation with the leksell gamma knife--first
      experience on 46 cases].
AB  - BACKGROUND: The aim of this non-comparative, consecutive case series is to
      evaluate the short-term results after endoresection of large uveal melanomas in
      combination with pretreatment with stereotactic gamma knife radiosurgery.
      METHODS: Between March 2000 and November 2002, forty-six patients with large
      uveal melanomas underwent stereotactic radiosurgery followed by endoresection of
      the tumour via a standard three-port vitrectomy including laser photocoagulation
      and silicone oil tamponade. The average tumour height was 9.5 mm. The minimum
      dose delivered to the tumour volume was 25 Gy. RESULTS: The median follow-up time
      was 410 days. In 40 cases (87 %), the eye was retained with a VA of 20/200 or
      better in 30 cases (65.2 %) and 20/63 or better in ten cases (21.7 %). In 12 eyes
      with a follow-up of >/= 0.5 years, the median VA was 20/80 after silicone oil
      removal and cataract surgery had been performed. Six eyes (13 %) were enucleated
      due to serious complications caused by the radiosurgery (3 cases) or
      endoresection (3 cases). In 13 patients (28.2 %), additional major surgery was
      required. Seven patients developed liver metastases during follow-up and six
      patients died. No local tumour recurrences were observed. CONCLUSIONS: Eyes with
      large uveal melanomas can be salvaged by stereotactic radiotherapy followed by
      endoresection.

PMID- 16804823
TI  - [Leucocoria in childhood].
AB  - BACKGROUND: There are a number of conditions in infants and young children which
      produce a white reflex in the pupillary area, termed leucocoria. In cases of
      leucocoria, retinoblastoma has to be excluded without delay. METHODS: We analysed
      data from consecutive children who were presented to our hospital because of
      leucocoria between January 1999 and June 2005. The analysis was performed by
      methods of descriptive statistics. RESULTS: Leucocoria was found in 83 eyes of 58
      children. Leucocoria was caused in most cases by congenital cataract (35 %),
      followed by malformations (18 %) (persistent hyperplastic primary vitreous,
      coloboma, disc anomaly, combined developmental abnormalities), hereditary
      vitreoretinal disorders (13 %), retinopathy of prematurity (12 %), trauma
      associated diseases (8 %). Five children suffered from retinoblastoma (6 %).
      Following in frequency were inflammatory disorders (5 %) and Coats' disease (2
      %). DISCUSSION: Several ocular conditions of childhood can clinically cause
      leucocoria. Knowledge of the clinical features that serve to differentiate
      retinoblastoma from simulating lesions may assist the clinician in arriving at
      the correct diagnosis.

PMID- 16804824
TI  - [Clinical aspects of retinopathy of prematurity. Results following diode laser
      coagulation].
AB  - Retinopathy of prematurity (ROP) represents a disease of the immature retina of
      preterm infants due to irregular vascularisation. The present article gives
      information about different parameters of the newborns (gestational age, birth
      weight, need of oxygen, stage of ROP) and shows the results concerning anatomical
      and functional aspects following diode laser treatment in 61 prematurely born
      babies, diagnosed and treated in a period of 5S years in the Hospital of the
      Ludwig Maximilians University. The mean +/- SD gestational age was 24.9 (+/-
      1.59) weeks, the mean +/- SD birth weight was 683 (+/- 174) grams. Diode laser
      treatment was performed at a mean +/- SD age of 36.14 (+/- 2.04) weeks. Stage 3
      retinopathy with "plus disease" was diagnosed in 95.5 % of the infants. In
      comparison to term born babies or preterm infants without ROP, the diode laser
      treated newborns showed a higher incidence of myopia (59 %). An unfavourable
      outcome in term of the anatomic situation was seen in 9.8 % of these babies.

PMID- 16804825
TI  - [Cystoid macular edema in a pseudophakic patient after several glaucoma
      procedures. Is local therapy with bimatoprost the reason?].
AB  - BACKGROUND: Prostaglandin-like drugs such as latanoprost (Xalatan), travoprost
      (Travatan) and bimatoprost (Lumigan) lower the intraocular pressure by improving
      the outflow of aqueous humor via the uveoscleral pathway. Up to now there is no
      report about a macular edema after the topical use of Lumigan eye drops in a
      pseudophakic patient with an intact posterior capsule. PATIENT: A 69-year-old
      pseudophakic patient with a 14-year history of glaucoma in pseudoexfoliation
      syndrome, revealed a cystoid macular edema after local treatment with bimatoprost
      . 6 months earlier a phakoemulsification followed by the insertion of a posterior
      intraocular lens was performed on the left eye. Due to an elevated intraocular
      pressure after the surgery, which could not be controlled either by several
      eyedrops, or by three more operations (one viscocanalostomy with mitomycin c, two
      cyclophotocoagulations), therefore, a final attempt with bimatoprost (Lumigan)
      was started. Two weeks later the patient complained of blurred vision, caused by
      a cystoid macular edema. RESULTS: After discontinuation of bimatoprost and
      initiation of a local and systemic anti-inflammatory therapy, the edema resolved
      and visual acuity recovered. CONCLUSION: Bimatoprost (Lumigan) , a synthetic
      prostamid is similar to human prostaglandins, especially to prostaglandin F
      (2alpha.) Although it does not bind to the same receptor, its side effects are
      comparable to those of common prostaglandin analogues. So far there are no
      reports about the manifestation of a macular edema after using bimatoprost in
      pseudophakic eyes with an intact posterior capsule. Even if three more operations
      followed the cataract surgery, we suspect that bimatoprost eyedrops can be held
      responsible for this. Therefore they should be used with great care and in clear
      indications, particularly in pseudophakic patients.

PMID- 16804826
TI  - [Bilateral anterior panuveitis as early manifestation of syphilis in a patient
      with HIV infection].
AB  - INTRODUCTION: Syphilis is a dangerous sexually transmitted infection which can be
      effectively treated with penicillin to avoid late-onset diseases. Even if
      syphilis is diagnosed an HIV infection should be excluded. PATIENT: A 32-year-old
      homosexual man complained about a decreased bilateral visual acuity after a
      feverish infection with lymphadenitis colli. With slit-lamp biomicroscopy a
      bilateral panuveitis with papillary edema, endothelial cells and episcleritis was
      found. After antimycotic and antiviral therapy, his visual acuity decreased and
      symptoms progressed. In the lab routine we found lues and HIV infections and
      started an intravenous penicillin therapy immediately. A few days later the
      symptoms improved and visual acuity increased. CONCLUSION: Lues serology should
      be incorporated into routine lab diagnostics to aid the detection and to start
      the right therapy as soon as possible.

PMID- 16804827
TI  - [The role of the ophthalmologist in the management of juvenile neuronal ceroid
      lipofuscinosis].
AB  - BACKGROUND: Neuronal ceroid lipofuscinoses (NCL) are storage diseases leading to
      severe somatic and mental deterioration with blindness and death. To date, there
      are no therapeutic options. Juvenile NCL (JNCL), also known as Batten's disease,
      is one of the most prevalent forms of NCL. MATERIALS AND METHODS: A 6-year-old
      boy with the primary diagnosis of retinitis pigmentosa was examined. The parents
      reported a rapid deterioration of vision during the past months. In view of this
      history, additional, non-ophthalmological diagnostic procedures have been
      performed (peripheral blood smear, molecular genetics). RESULTS: The eye
      examination showed a considerable reduction of visual acuity, a concentric visual
      field constriction, an extinguished electroretinogram and a bull's eye
      maculopathy. The peripheral blood smear revealed vacuolated lymphocytes.
      Molecular genetic investigation confirmed the diagnosis of juvenile NCL by
      detecting a homozygous (1-kb deletion of the CLN3-gene). CONCLUSIONS: The
      ophthalmologist plays a key role for an early diagnosis of juvenile NCL. An early
      diagnosis is important for the affected families because only then they can
      handle this stroke of fate.

PMID- 16804829
TI  - Hemophilia therapy and blood-borne pathogen risk.
AB  - For a brief period, modern medical science was considered to have relegated
      infectious disease to that of a minor clinical challenge. However, several
      infectious diseases have emerged or re-emerged in recent years, raising
      epidemiological concerns, as well as issues over the availability of effective
      measures of control and treatment. Invariably, these infectious agents have been
      studied carefully in relation to the safety of blood products, often resulting in
      concern and action. Emerging diseases arise from many sources. Some are the
      result of viruses crossing the species barrier from animals to humans. In
      addition, combinations of these newly identified viruses may make each more
      difficult to treat, as in the case of human immunodeficiency virus and hepatitis
      C virus coinfection. Still others can arise from completely new biological
      mechanisms, such as the prion disease variant Creutzfeldt-Jacob disease, which
      has spread from infected cattle to humans, particularly in the United Kingdom.
      The emergence of new viruses and new disease sources has had a significant impact
      on coagulation factor therapies and blood donation policies. We must deal with
      these multiple threats and their potential to compromise the safety of our blood
      supply.

PMID- 16804830
TI  - Inhibitor development in hemophiliacs: the roles of genetic versus environmental
      factors.
AB  - Approximately 5 to 7% of patients with hemophilia A have inhibitory antibodies to
      factor (F) VIII, which increases to approximately 13% in patients with severe
      disease. The strongest determinant of the risk of inhibitor development
      identified is the type of mutation in the FVIII gene that gives rise to the
      disease. However, accumulating evidence clearly indicates that other genetic
      factors (e.g., major histocompatibility complex alleles and other immune
      modulatory genes) and factors associated with treatment (e.g., type of FVIII
      concentrate, route of administration, and age of first exposure) may also
      influence the risk of inhibitor development. There is much interest in
      identifying such genetic and treatment-related factors to help minimize the risk
      of inhibitor development and improve treatment outcomes.

PMID- 16804831
TI  - Current and future approaches to inhibitor management and aversion.
AB  - Immune tolerance induction (ITI) is the most common approach used to eliminate
      inhibitors that develop in hemophilia A patients following exposure to factor (F)
      VIII therapy. ITI generally requires ongoing long-term exposure to factor
      replacement therapy using FVIII or FIX. Although plasma-derived products have
      been the mainstay of ITI therapy in the past, recent data indicate that high
      purity (i.e., recombinant) rFVIII products are probably equally effective. For
      patients who have failed to respond to ITI treatment, or for those at high risk
      to do so, immunosuppressive therapy may be helpful. Rituximab has demonstrated a
      possible clinical benefit in hemophilic and nonhemophilic patients developing
      FVIII inhibitors, but benefit in those with congenital hemophilia and inhibitors
      has not been established and more extensive clinical studies are needed. More
      recently, research on reducing the incidence of inhibitor development has
      included mutagenizing key epitopes of the FVIII antigenic molecule to alter its
      immunogenicity without affecting biological activity, as well as induction of
      tolerance by gene therapy with immunodominant A2 and C2 domains of FVIII
      presented by B cells as immunoglobulin fusion proteins.

PMID- 16804832
TI  - New approaches to using FEIBA in the treatment of inhibitor patients.
AB  - Managing hemophilia becomes particularly difficult in patients with inhibitory
      antibodies, especially in those requiring surgery or with refractory bleeding
      events. Equally challenging are those patients who develop autoantibodies against
      factor VIII (FVIII) in the absence of a prior history of FVIII deficiency
      (acquired hemophilia). Physicians seeking both short- and long-term treatment
      strategies for bleeding events must often rely on FVIII-bypassing agents such as
      activated prothrombin complex concentrate (e.g., factor eight bypassing activity
      [FEIBA VH, Baxter BioScience, Westlake Village, CA]) or recombinant factor VIIa
      (rFVIIa [NovoSeven, NovoNordisk, Bagsvaerd, Denmark]). Surgical procedures in
      patients with inhibitors present a considerable challenge, from both a risk
      benefit and a cost-benefit aspect. Hemostasis is difficult to achieve in these
      patients and new treatment options are being explored. Similarly challenging are
      refractory bleeds, the management of which is likely to benefit from a systematic
      treatment approach.

PMID- 16804833
TI  - Managing the pediatric patient and the adolescent/adult transition.
AB  - Healthcare management of the developing child with hemophilia presents several
      difficulties. Determining the optimum medication dose is complicated by the
      difficulty of performing pharmacokinetic studies in children and the fact that
      extrapolation from data collected in adults is generally unsatisfactory. Even
      when pediatric pharmacokinetic data are available, accumulating evidence suggests
      that there can be wide interindividual differences; age and size are important
      contributing factors. Achieving the venous access necessary for blood factor
      administration is frequently difficult in the small child. Preliminary results
      suggest that an arteriovenous fistula may be an appropriate option in some
      patients. Finally, there is the question of whether prophylactic therapy should
      be discontinued as patients enter adulthood. This article provides insights for
      managing this challenging patient population.

PMID- 16804834
TI  - Future aspects of hemophilia research and care.
AB  - Key issues in the management of patients with hemophilia include a thorough
      understanding of the mechanisms of blood coagulation and the complications that
      follow recurrent joint bleeding. Monoclonal antibodies are powerful tools for
      dissecting the intrinsic coagulation pathway and deriving reagents that could
      lead, on the long term, to the identification of molecules that enhance, or
      perhaps even replace factor (F) VIII concentrates in the management of hemophilia
      A. In recent in vitro experiments, it was demonstrated that plasmatic thrombin
      generation and intrinsic FX activation was enhanced by each of two FIXa-specific
      monoclonal antibodies, one of which had FIXa-agonistic activity only, whereas the
      other enhanced the activity of the intrinsic FX-activating complex (FVIIIa/FIXa)
      by at least two distinct mechanisms. Hemophilic synovitis, an inflammatory and
      proliferative disorder in patients with hemophilia, is the result of bleeding
      into joints and can lead to debilitating arthritis and chronic arthropathy. A
      major causative factor in the development of hemophilic synovitis is blood
      derived iron deposited in joints. FVIII-deficient knockout mice with trauma
      induced hemarthrosis serve as a model system for hemophilic synovitis,
      reproducing the histological features observed in patients. In addition, this
      animal model recapitulates the observations made in vitro with synovial cell
      cultures stimulated by iron. These in vitro experiments suggested a role for iron
      as an agent capable of inducing proliferation and oncogene expression by human
      and murine synovial fibroblasts. A better understanding of iron-regulated
      pathways and oncogene expression may lay the groundwork for targeted molecular
      interventions in hemophilic synovitis.

PMID- 16804835
TI  - The next generation of hemophilia treatment specialists.
AB  - We currently are witnessing a serious attrition of physicians specializing in
      hemophilia treatment in Europe and the United States while most physicians who
      complete training in hematology-oncology choose oncology practice as their
      career. Nevertheless, recent therapeutic developments, including advances in
      prophylaxis and inhibitor management, have renewed the demand for experts in
      hemophilia and related disorders. To meet this demand, several specialty training
      programs have been developed in the United States and Europe, specifically the
      International Course in Hemophilia in Malmo, Sweden, the Children's Hospital of
      Los Angeles International Pediatric Hemostasis and Thrombosis Program, and the
      Baxter/National Hemophilia Foundation Fellowship Programs. The purpose of these
      programs is to enhance the clinical expertise and further the professional
      development of individuals dedicated to treating patients with coagulation
      disorders.

PMID- 16804836
TI  - Paradoxical increase in circulating Aspergillus antigen during treatment with
      caspofungin in a patient with pulmonary aspergillosis.
AB  - A paradoxical increase in circulating Aspergillus antigen was observed during
      treatment with caspofungin in a patient with proven invasive aspergillosis. With
      the exception of treatment with the echinocandin, no other factors were found
      that might explain this clinical observation, which was supported by experiments
      done in vitro.

PMID- 16804837
TI  - The spread of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae to
      upstate New York.
AB  - Klebsiella pneumoniae carbapenemases (KPCs) have previously been identified in
      distinct geographic locations. We report the spread of KPC-2 to upstate New York.
      Our intention is to alert clinicians to problems encountered in identifying KPC
      containing isolates. Possible errors as a result of inferring susceptibility of
      untested carbapenems from the routine antibiogram using agar-based methodology or
      microdilution testing are discussed.

PMID- 16804838
TI  - Safety and completion rate of short-course therapy for treatment of latent
      tuberculosis infection.
AB  - BACKGROUND: Nine months of isoniazid therapy is the recommended regimen for
      treatment of latent tuberculosis infection, but low completion rates are a
      serious problem. The search for shorter regimens, compared with the standard
      isoniazid regimen, is of vital importance. We describe our experience using short
      course regimens for the treatment of latent tuberculosis infection. METHODS: We
      conducted a nonrandomized, observational study of 459 patients in a county health
      department from June 2000 to January 2006. Short-course therapy was defined as
      pyrazinamide and rifampin taken daily or twice weekly for 2 months or rifampin
      taken daily for 4-6 months. Conventional therapy consisted of a 9-month regimen
      of isoniazid. Liver function testing was performed for both groups in accordance
      with clinical guidelines. Treatment completion and hepatotoxicity (according to
      the World Health Organization classification) were determined for the short
      course and conventional therapy groups. RESULTS: Treatment was completed by 241
      (77.7%) of 310 patients in the short-course group and by 98 (65.8%) of 149
      patients in the isoniazid group (P = .009). Moderate to severe hepatotoxicity
      (grades 3 and 4) occurred in 6.1% of patients receiving short-course therapy and
      in 2.0% of patients receiving isoniazid (P=.09). The hepatotoxicity observed in
      the short-course group was confined to patients receiving pyrazinamide and
      rifampin daily and was self limited in all cases after the medications were
      discontinued. CONCLUSIONS: The rate of treatment completion was significantly
      higher with short-course regimens, compared with the isoniazid regimen. Although
      the overall risk of hepatotoxicity in patients receiving pyrazinamide and
      rifampin daily for the treatment of latent tuberculosis infection was higher,
      liver functions returned to normal after the medications were discontinued.

PMID- 16804839
TI  - A cohort study among university students: identification of risk factors for
      Epstein-Barr virus seroconversion and infectious mononucleosis.
AB  - BACKGROUND: A vaccine against Epstein-Barr virus (EBV) infection is in clinical
      trials. Up-to-date information on risk factors for EBV infection and infectious
      mononucleosis (IM) among young adults is required to inform a vaccination
      strategy. METHODS: We carried out a prospective study on a cohort of university
      students. All EBV-seronegative students were asked to report symptoms of IM and
      were followed up 3 years later to undergo repeat EBV testing and to complete a
      lifestyle questionnaire. EBV typing was performed for these subjects, as well as
      for students who were EBV seropositive at enrollment and for additional students
      with IM. RESULTS: A total of 510 students (25%) who took part in the study were
      EBV seronegative when they entered the university; of the 241 who donated a
      second blood sample 3 years later, 110 (46%) had seroconverted to EBV, 27 (25%)
      of whom developed IM [corrected] Penetrative sexual intercourse was a risk factor
      for EBV seroconversion (P = .004), but neither condom use nor oral sex
      significantly altered the rate of seroconversion. EBV type 1 was significantly
      overrepresented in IM, compared with silent seroconversion (P = .001).
      CONCLUSIONS: Our findings suggest that acquisition of EBV is enhanced by
      penetrative sexual intercourse, although transmission could occur through related
      sexual behaviors, such as "deep kissing." We also found that EBV type 1 infection
      is significantly more likely to result in IM. Overall, the results suggest that a
      large EBV type 1 load acquired during sexual intercourse can rapidly colonize the
      B cell population and induce the exaggerated T cell response that causes IM.
      Thus, IM could, perhaps, be prevented with a vaccine that reduces the viral load
      without necessarily inducing sterile immunity.

PMID- 16804840
TI  - Human bocavirus: prevalence and clinical spectrum at a children's hospital.
AB  - BACKGROUND: Molecular methods of pathogen discovery have recently led to the
      description of several new respiratory viruses. Human bocavirus (HBoV), a
      proposed member of the family Parvoviridae, is one of the most recently described
      respiratory viruses. Initial reports indicate that HBoV is a common cause of
      respiratory tract infection in children. METHODS: A total of 1474 nasal scraping
      specimens collected over a 20-month period were screened by polymerase chain
      reaction for the presence of HBoV nucleic acid. Positive results were confirmed
      with a second polymerase chain reaction assay from a different genomic region.
      The medical records of patients with positive results were reviewed for
      demographic and clinical data. RESULTS: HBoV DNA was identified in 82 samples
      (5.6%). The peak rate of HBoV infection occurred during the period of March
      through May in both 2004 and 2005. Sixty-three percent of infected patients were
      <12 months of age. The most common symptoms were cough, rhinorrhea, and fever.
      Other symptoms of interest included diarrhea and a "paroxysmal" cough that was
      clinically suspected to be caused by Bordetella pertussis. CONCLUSIONS: HBoV DNA
      is commonly present in children with upper and lower respiratory tract
      infections. The presence of a pertussis-like cough and diarrhea in association
      with HBoV infection merits further investigation.

PMID- 16804841
TI  - Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in
      young Haitian children.
AB  - BACKGROUND: Mannose-binding lectin (MBL) is a component of the innate immune
      response and binds microbial surfaces through carbohydrate recognition domains.
      MBL deficiency may contribute to susceptibility to a variety of infectious
      diseases, particularly in young children. MBL binds to the Cryptosporidium
      sporozoite and may be important in resistance to cryptosporidiosis. METHODS: We
      studied the association of serum MBL levels and cryptosporidiosis in a case
      control study of young Haitian children with cryptosporidiosis versus children
      who were control subjects. RESULTS: Ninety-nine children were enrolled, as
      follows: 49 children with cryptosporidiosis, 41 healthy controls, and 9 children
      with diarrhea from other causes. Case children were more malnourished than
      controls, and 49% had persistent or chronic diarrhea. At enrollment, mean serum
      MBL levels were markedly lower in children with cryptosporidiosis (P = .002), as
      was the number of children with an MBL deficiency of < or = 70 ng/mL (P = .005).
      In multivariate analysis, the association of cryptosporidiosis and MBL deficiency
      persisted (P = .002; adjusted odds ratio, 22.4), as did the association of
      cryptosporidiosis with general malnutrition. The subset of children with
      cryptosporidiosis and MBL deficiency were more likely to be male (P = .025).
      CONCLUSIONS: MBL may be an important component of innate immune protection
      against Cryptosporidium infection in young children. Additional studies are
      necessary to determine whether MBL intestinal losses, deficient epithelial
      expression, and/or genetic polymorphisms in the MBL gene contribute to MBL
      deficiency in cryptosporidiosis and other enteric infections in young children.

PMID- 16804842
TI  - Association of mannose-binding lectin deficiency with cryptosporidiosis.

PMID- 16804843
TI  - Plasmid-mediated quinolone resistance in non-Typhi serotypes of Salmonella
      enterica.
AB  - BACKGROUND: Serious infections with Salmonella species are often treated with
      fluoroquinolones or extended-spectrum beta-lactams. Increasingly recognized in
      Enterobacteriaceae, plasmid-mediated quinolone resistance is encoded by qnr
      genes. Here, we report the presence of qnr variants in human isolates of non
      Typhi serotypes of Salmonella enterica (hereafter referred to as non-Typhi
      Salmonella) from the United States National Antimicrobial Resistance Monitoring
      System for Enteric Bacteria. METHODS: All non-Typhi Salmonella specimens from the
      United States National Antimicrobial Resistance Monitoring System for Enteric
      Bacteria collected from 1996 to 2003 with ciprofloxacin minimum inhibitory
      concentrations > or = 0.06 microg/mL (233 specimens) and a subset with minimum
      inhibitory concentrations < or = 0.03 microg/mL (102 specimens) were screened for
      all known qnr genes (A, B, and S) by polymerase chain reaction. For isolates with
      positive results, qnr and quinolone resistance-determining region sequences were
      determined. Plasmids containing qnr genes were characterized by conjugation or
      transformation. RESULTS: Conjugative plasmids harboring qnrB variants were
      detected in 7 Salmonella enterica serotype Berta isolates and 1 Salmonella
      enterica serotype Mbandaka isolate. The S. Mbandaka plasmid also had an extended
      spectrum beta -lactamase. Variants of qnrS on nonconjugative plasmids were
      detected in isolates of Salmonella enterica serotype Anatum and Salmonella
      enterica serotype Bovismorbificans. CONCLUSIONS: Plasmid-mediated quinolone
      resistance appears to be widely distributed, though it is still uncommon in non
      Typhi Salmonella isolates from the United States, including strains that are
      quinolone susceptible by the criteria of the Clinical and Laboratory Standards
      Institute (formerly the National Committee for Clinical Laboratory Standards).
      The presence of this gene in non-Typhi Salmonella that causes infection in humans
      suggests potential for spread through the food supply, which is a public health
      concern.

PMID- 16804844
TI  - The monocyte chemoattractant protein-1 gene polymorphism is associated with
      cardiomyopathy in human chagas disease.
AB  - BACKGROUND: Only a subset of individuals infected with Trypanosoma cruzi develop
      chronic Chagas cardiomyopathy (CCC). Familial aggregation of CCC in areas of
      endemicity indicates that susceptibility may be genetic, which may be a plausible
      explanation for why only one-third of T. cruzi-infected individuals develop CCC.
      The monocyte chemoattractant protein-1 (CCL2/MCP-1) has been shown to enhance the
      uptake of T. cruzi in murine macrophages and to up-regulate the inducible nitric
      oxide synthase/nitric oxide system, with a consequent increased production of
      nitric oxide that controls the replication of the parasite. METHODS: We assessed
      CCL2 variants at position -2518A/G, which are known to influence transcriptional
      activity, by polymerase chain reaction and restriction fragment-length
      polymorphism in 245 individuals, all of whom were infected with T. cruzi. One
      hundred sixty-nine patients had CCC, and 76 were asymptomatic. RESULTS: Genotype
      distributions differed between the CCC and asymptomatic groups (chi2 = 9.4; P =
      .009), with an excess of genotypes with the A allele (AA + AG) in the CCC group.
      Among patients with CCC, 5% were homozygous for the G allele, compared with 16%
      of the asymptomatic subjects (odds ratio [OR], 4.1; 95% confidence interval [CI],
      1.7-11; P = .001). A similar trend was observed when individuals heterozygous for
      the G allele were compared with individuals homozygous for the G allele between
      the CCC and asymptomatic groups (OR, 2.7; 95% CI, 0.97-7.2; P = .026). The A
      allele seems to confer susceptibility to CCC (OR, 1.9; 95% CI, 1.3-2.9; P =
      .001). CONCLUSIONS: The CCL2 variant correlated with a low transcriptional level
      behaves as a genetic modifier of clinical outcome for T. cruzi infection, and
      subjects with the CCL2 -2518AA genotype have a 4-fold greater risk of developing
      CCC than do those without this genotype.

PMID- 16804845
TI  - Rotavirus serotype G9 is associated with more-severe disease in Latin America.
AB  - The association between rotavirus serotypes and severity is not well established.
      Analysis of a clinical trial conducted in Latin America points at more-severe
      disease associated with serotype G9. Thus, demonstration of efficacy against G9
      will be an important asset of any rotavirus vaccine to be introduced into a Latin
      American country or any country where G9 has been shown to be prevalent.

PMID- 16804846
TI  - Rotavirus genotypes and severity of diarrheal disease.

PMID- 16804847
TI  - Genetic diversity of invasive strains of Haemophilus influenzae type b before and
      after introduction of the conjugate vaccine in Italy.
AB  - We determined the genotypes of 95 invasive Haemophilus influenzae type b (Hib)
      strains collected before and after introduction of widespread Hib vaccination in
      Italy. No substantial change in genetic diversity was highlighted by pulsed-field
      gel electrophoresis. However, an upward temporal trend in proportion of strains
      possessing multiple copies of the capsulation b locus was detected (P = .03).

PMID- 16804848
TI  - The surgical infection prevention and surgical care improvement projects:
      national initiatives to improve outcomes for patients having surgery.
AB  - Among the most common complications that occur after surgery are surgical site
      infections and postoperative sepsis, cardiovascular complications, respiratory
      complications (including postoperative pneumonia), and thromboembolic
      complications. Patients who experience postoperative complications have
      dramatically increased hospital length of stay, hospital costs, and mortality
      rates. The Centers for Medicare & Medicaid Services, in collaboration with the
      Centers for Disease Control and Prevention, has implemented the Surgical
      Infection Prevention Project to decrease the morbidity and mortality associated
      with postoperative surgical site infections. More recently, the Surgical Care
      Improvement Project, a national quality partnership of organizations committed to
      improving the safety of surgical care, has been announced. This review will
      provide an update from the Surgical Infection Prevention Project and provide an
      introduction to the Surgical Care Improvement Project.

PMID- 16804849
TI  - Adenovirus infections in transplant recipients.
AB  - Adenoviruses are increasingly recognized as contributors to morbidity and
      mortality among stem cell and solid-organ transplant recipients. Clinical
      presentations range from asymptomatic viremia to respiratory and gastrointestinal
      disease, hemorrhagic cystitis, and severe disseminated illness. The limited
      clinical data available support the use of cidofovir for many of these illnesses.
      Prospective studies are needed to better understand the pathogenesis of and
      therapeutic options for adenoviral infections in this patient population.

PMID- 16804850
TI  - Creutzfeldt-Jakob disease: a rare cause of dementia in elderly persons.
AB  - Creutzfeldt-Jakob disease (CJD) exists in inherited, acquired (variant and
      iatrogenic), and spontaneous (sporadic) forms. Although iatrogenic and variant
      forms of CJD usually affect relatively young persons, all forms may affect
      elderly persons, especially sporadic CJD. Sporadic CJD is a rare cause of
      dementia among middle-aged and elderly persons, and typical cases are clinically
      fairly distinct from more common forms of neurodegenerative dementias. However,
      clinical diagnosis can be a challenge for those who are not experienced with the
      disease. Fortunately, certain investigations can be very helpful. Although many
      cases of CJD (especially sporadic CJD) are not thought to be acquired illnesses,
      there is still a potential for onward transmission, and certain precautions are
      necessary to protect public health.

PMID- 16804851
TI  - Management of herpes simplex virus type 2 infection in HIV type 1-infected
      persons.
AB  - Human immunodeficiency virus type 1 (HIV-1)-infected persons have high rates of
      herpes simplex virus type 2 (HSV-2) infection, ranging from 50% to 90% in studies
      of HIV-infected populations from different parts of the world. Genital herpes in
      persons with HIV type 1 (HIV-1) infection is associated with more-severe and
      chronic lesions, as well as increased rates of asymptomatic genital shedding of
      HSV-2. Nucleoside analogues (acyclovir, valacyclovir, and famciclovir) decrease
      the frequency and severity of HSV-2 recurrences and asymptomatic HSV-2
      reactivation and are effective, safe, well-tolerated drugs in patients with HIV-1
      infection. These anti-HSV drugs may result in additional clinical and public
      health benefits for persons with HIV-1 and HSV-2 coinfection by decreasing HIV-1
      levels in the blood and genital tract. Given these benefits, HIV-1-infected
      persons should be routinely tested for HSV-2 infection using type-specific
      serologic tests. Persons with HSV-2 infection should be offered HSV-2 education
      and treatment options. Studies to quantify the potential clinical and public
      health benefits of treating individuals who have HIV-1 and HSV-2 coinfection with
      anti-HSV therapy are underway.

PMID- 16804852
TI  - A comparison of miltefosine and sodium stibogluconate for treatment of visceral
      leishmaniasis in an Ethiopian population with high prevalence of HIV infection.
AB  - BACKGROUND: Antimonials are the mainstay of visceral leishmaniasis (VL) treatment
      in Africa. The increasing incidence of human immunodeficiency virus (HIV)
      coinfection requires alternative safe and effective drug regimens. Oral
      miltefosine has been proven to be safe and effective in the treatment of Indian
      VL but has not been studied in Africa or in persons with HIV and VL coinfection.
      METHODS: We compared the efficacy of miltefosine and sodium stibogluconate (SSG)
      in the treatment of VL in persons in Ethiopia. A total of 580 men with
      parasitologically and/or serologically confirmed VL were randomized to receive
      either oral miltefosine (100 mg per day for 28 days) or intramuscular SSG (20
      mg/kg per day for 30 days). RESULTS: The initial cure rate was 88% in both
      treatment groups. Mortality during treatment was 2% in the miltefosine group,
      compared with 10% in the SSG group. Initial treatment failure was 8% in the
      miltefosine group, compared with 1% in the SSG group. Among the 375 patients
      (65%) who agreed to HIV testing, HIV seroprevalence was 29%. Among patients not
      infected with HIV, initial cure, mortality, and initial treatment failure rates
      were not significantly different (94% vs. 95%, 1% vs. 3%, and 5% vs. 1% for the
      miltefosine and SSG groups, respectively). Initial treatment failure with
      miltefosine occurred in 18% of HIV-coinfected patients, compared with treatment
      failure in 5% of non-HIV-infected patients. At 6 months after treatment, 174
      (60%) of the 290 miltefosine recipients and 189 (65%) of the 290 SSG recipients
      experienced cure; 30 (10%) of 290 in the miltefosine group and 7 (2%) of 290 in
      the SSG group experienced relapse, and the mortality rate was 6% in the
      miltefosine group, compared with 12% in the SSG group. HIV-infected patients had
      higher rates of relapse (16 [25%] of 63 patients), compared with non-HIV-infected
      patients (5 [5%] of 131). CONCLUSIONS: Treatment with miltefosine is equally
      effective as standard SSG treatment in non-HIV-infected men with VL. Among HIV
      coinfected patients, miltefosine is safer but less effective than SSG.

PMID- 16804853
TI  - Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and
      hepatitis C virus genotype 3 infection in HIV-seropositive patients.
AB  - BACKGROUND: We conducted a study to determine the prevalence and factors
      associated with hepatic steatosis in human immunodeficiency virus (HIV)
      seropositive patients with hepatitis C and to investigate whether steatosis is
      associated with liver fibrosis. METHODS: Retrospective chart reviews were
      conducted in 4 hospitals that serve community-based and incarcerated HIV-infected
      patients who had undergone a liver biopsy for evaluation of hepatitis C virus
      (HCV) infection during the period of 2000-2003. Demographic characteristics and
      medication and laboratory data were collected from the time of the biopsy. A
      pathologist blinded to all clinical data evaluated the specimens. The primary
      outcome was presence or absence of steatosis. RESULTS: Of 260 HIV-HCV-coinfected
      patients, 183 met inclusion criteria and had a biopsy specimen adequate for
      review. Steatosis was present in 69% of patients (graded as minimal in 31%, mild
      in 27%, moderate in 18%, and severe in 1%). Factors associated with steatosis
      included use of dideoxynucleoside analogues, such as didanosine and stavudine
      (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.55-13.82). There was a
      trend toward presence of steatosis and use of other nucleoside analogues or
      infection with HCV genotype 3 (OR, 2.65 [95% CI, 0.95-7.41] and 3.38 [95% CI,
      0.86-13.28], respectively). The presence of steatosis was associated with
      fibrosis (OR, 1.37; 95% CI, 1.03-1.81). CONCLUSIONS: In this multiracial
      population of HIV-HCV-coinfected patients, steatosis was prevalent and was
      associated with severity of liver fibrosis. Use of nucleoside analogues
      (particularly didanosine and stavudine) and HCV genotype 3 infection were
      associated with hepatic steatosis. The development of steatosis is multifactorial
      in nature and may play a contributory role in the progression of liver disease in
      HIV-infected patients.

PMID- 16804854
TI  - Dideoxynucleoside analogues should be used cautiously in patients with hepatic
      steatosis.

PMID- 16804855
TI  - HIV type 1 RNA level as a clinical indicator of renal pathology in HIV-infected
      patients.
AB  - To determine the value of human immunodeficiency virus type 1 (HIV-1) RNA level
      in distinguishing HIV-associated nephropathy from non-HIV-associated nephropathy
      renal pathological conditions, we retrospectively compared renal
      histopathological findings for 86 HIV-infected patients according to HIV-1 RNA
      levels. We found that HIV-associated nephropathy was unlikely among patients with
      HIV-1 RNA levels <400 copies/mL. Hypertensive vascular disease surpassed HIV
      associated nephropathy as the most common renal pathological finding among the
      entire cohort. HIV-1 RNA level did not correlate with renal survival.

PMID- 16804856
TI  - Acinetobacter infection: what was the true impact during the Vietnam conflict?

PMID- 16804858
TI  - Coccidioidal meningitis.

PMID- 16804859
TI  - Assessment of carriage of Haemophilus influenzae type a after a case of invasive
      disease.

PMID- 16804860
TI  - Control of nosocomial methicillin-resistant Staphylococcus aureus infection.

PMID- 16804861
TI  - Rash as a prognostic factor in West Nile virus disease.

PMID- 16804863
TI  - Attributable mortality of Acinetobacter baumannii infection among critically ill
      patients.

PMID- 16804864
TI  - Magnetic acoustic resonance immunoassay (MARIA): a multifrequency acoustic
      approach for the non-labelled detection of biomolecular interactions.
AB  - A unique sensing platform, comprising an electromagnetic field detector and an
      acoustic resonator, has been used as a wireless system for remote sensing of
      biorecognition events. The MARS (Magnetic Acoustic Resonator Sensor) technique
      has proven useful for detecting the formation of protein multilayers derived from
      specific binding phenomena. The technique enables multifrequency analysis,
      without the need of electrodes attached to the sensing element, and also
      facilitates the in situ surface modification of the substrate for antibody
      attachment. The MARS sensor was utilized as the platform on which a standard
      immunoassay was carried out. Two different conditions for the attachment of the
      first antibody to the quartz surface were tested: (i) Adsorption of the antibody
      onto the surface of a bare quartz disc; (ii) covalent immobilization of the
      antibody to a chemically modified quartz surface. Both methods can be
      successfully utilized for the 'label-less' detection of the biorecognition event
      between goat IgG and anti-goat IgG by analysis of the multifrequency spectrum.
      Covalent attachment of the primary antibody results in a more efficient
      immobilization, with higher surface density, and a consistently enhanced response
      for the binding of the secondary antibody. This approach will be of interest to
      life scientists and biochemists that require high performance assay methodologies
      that do not use chemical labels.

PMID- 16804866
TI  - Prospective study of fetal DNA in serum and disease activity during pregnancy in
      women with inflammatory arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) usually improves during pregnancy and recurs
      postpartum. Fetal cells and cell-free DNA reach the maternal circulation during
      normal pregnancy. The present study investigated dynamic changes in levels of
      fetal DNA in serum from women with RA and inflammatory arthritis during and after
      pregnancy to test the hypothesis that the levels of circulating fetal DNA
      correlate with arthritis improvement. METHODS: Twenty-five pregnant patients were
      prospectively studied. A real-time quantitative polymerase chain reaction panel
      targeting unshared, paternally transmitted HLA sequences, a Y chromosome-specific
      sequence, or an insertion sequence within the glutathione S-transferase M1 gene
      was used to measure cell-free fetal DNA. Results were expressed as fetal genomic
      equivalents per milliliter (gE/ml) of maternal serum. Physical examinations were
      conducted during and after pregnancy. RESULTS: Levels of fetal DNA in women with
      improvement in or remission of arthritis were higher than those in women with
      active disease, especially in the third trimester. Overall, an inverse
      relationship between serum fetal DNA levels and disease activity was observed (P
      < 0.001). Serum fetal DNA increased with advancing gestation, reaching median
      levels of 24 gE/ml (range 0-334), 61 gE/ml (range 0-689), and 199 gE/ml (range 0
      2,576) in the first, second, and third trimesters, respectively, with fetal DNA
      clearance observed postpartum. Arthritis improvement was initially noted in the
      first trimester for most patients, increased further or was sustained with
      advancing gestation, and was active postpartum. CONCLUSION: Changes in serum
      fetal DNA levels correlated with arthritis improvement during pregnancy and
      recurrence postpartum. Immunologic mechanisms by which pregnancy might modulate
      RA activity are described.

PMID- 16804865
TI  - Identification of genes modulated in rheumatoid arthritis using complementary DNA
      microarray analysis of lymphoblastoid B cell lines from disease-discordant
      monozygotic twins.
AB  - OBJECTIVE: To identify disease-specific gene expression profiles in patients with
      rheumatoid arthritis (RA), using complementary DNA (cDNA) microarray analyses on
      lymphoblastoid B cell lines (LCLs) derived from RA-discordant monozygotic (MZ)
      twins. METHODS: The cDNA was prepared from LCLs derived from the peripheral blood
      of 11 pairs of RA-discordant MZ twins. The RA twin cDNA was labeled with cy5
      fluorescent dye, and the cDNA of the healthy co-twin was labeled with cy3. To
      determine relative expression profiles, cDNA from each twin pair was combined and
      hybridized on 20,000-element microarray chips. Immunohistochemistry and real-time
      polymerase chain reaction were used to detect the expression of selected gene
      products in synovial tissue from patients with RA compared with patients with
      osteoarthritis and normal healthy controls. RESULTS: In RA twin LCLs compared
      with healthy co-twin LCLs, 1,163 transcripts were significantly differentially
      expressed. Of these, 747 were overexpressed and 416 were underexpressed. Gene
      ontology analysis revealed many genes known to play a role in apoptosis,
      angiogenesis, proteolysis, and signaling. The 3 most significantly overexpressed
      genes were laeverin (a novel enzyme with sequence homology to CD13), 11beta
      hydroxysteroid dehydrogenase type 2 (a steroid pathway enzyme), and cysteine
      rich, angiogenic inducer 61 (a known angiogenic factor). The products of these
      genes, heretofore uncharacterized in RA, were all abundantly expressed in RA
      synovial tissues. CONCLUSION: Microarray cDNA analysis of peripheral blood
      derived LCLs from well-controlled patient populations is a useful tool to detect
      RA-relevant genes and could help in identifying novel therapeutic targets.

PMID- 16804867
TI  - Accordion BIRD-HMBC experiments: improved one-bond correlation suppression in
      accordion heteronuclear multiple-bond correlation-type experiments.
AB  - Modifications of the BIRD-HMBC experiment, in which the accordion principle and a
      constant time period have been introduced, are presented. With the simple
      accordion BIRD-HMBC, the use of a BIRD(r, X) element in the middle of the
      variable long-range couplings evolution period efficiently eliminates unwanted
      (1)J(CH) signals and samples a broad range of long-range heteronuclear couplings.
      While the accordion BIRD-HMBC experiment shows reduced F(1) modulation, superior
      suppression of unwanted (1)J(CH) signals and sensitivity comparable to the ACCORD
      HMBC, the addition of another constant time period suppresses F(1) modulation due
      to (1)H-(1)H coupling, while preserving the excellent suppression of unwanted
      (1)J(CH) signals. The constant-time (CT) accordion BIRD-HMBC experiment combines
      sensitivity similar to the CIGAR-HMBC and superior suppression of unwanted
      (1)J(CH) signals. Results of identically optimized ACCORD-HMBC, accordion BIRD
      HMBC, CT accordion BIRD-HMBC and CIGAR-HMBC experiments performed on a sample of
      strychnine are compared and discussed.

PMID- 16804868
TI  - Substituent effects on 15N and 13C NMR chemical shifts of 3-phenylisoxazoles: a
      theoretical and spectroscopic study.
AB  - The synthesis and assignment of 15N and 13C NMR signals of the isoxazole ring in
      a series of para-substituted 3-phenyl derivatives are reported. DFT calculations
      of 15N and 13C chemical shifts are presented and compared to observed values.
      Substituent effects are interpreted in terms of the Hammett correlation and
      calculated bond orders.

PMID- 16804869
TI  - 1H and 13C NMR assignments and X-ray structures for three monocyclic
      benzoannelated dilactam polyethers.
AB  - Three monocyclic polyether dilactams, 17,18-dihydro-5H, 9H
      dibenzo[e,n]1,4,10,7,13trioxadiazacyclopentadecine-6,10(7H,11H)-dione (1);
      9,10,20,21-tetrahydro-5H, 12H
      dibenzo[e,q]1,4,10,13,7,16tetraoxadiazacyclooctadecine-6, 13(7H,14H)-dione (2);
      and 6,7,9,10-tetrahydro-16H, 20H-dibenzo[h,q]1,4,7,13,
      10,16tetraoxadiazacyclooctadecine-17, 21(18H,22H)-dione (3) were isolated during
      the synthesis of several benzoannelated cryptands. The complete assignments of
      the 1H and 13C NMR spectra of 1, 2 and 3 in CDCl3 were made using gCOSY, gHMBC,
      gHMQC, HMQC, HSQC, and NOESY 1D techniques. The ortho (H2) benzene protons show
      significant downfield shifts (1.16-1.43 ppm) that are consistent with an
      exodentate orientation for the amide carbonyl groups. The X-ray crystal
      structures of 1, 2 and 3 show that the carbonyl groups adopt an exodentate
      conformation in the solid state.

PMID- 16804870
TI  - Incidence and patterns of recurrence after resection for cure of colonic cancer
      in a well defined population.
AB  - BACKGROUND: The aim of this study was to determine the incidence and patterns of
      failure following potentially curative surgery of colonic cancer. METHODS: Data
      were obtained from the cancer registry of the Cote-d'Or (France). Data on 2657
      patients who had resection for cure of colonic cancer between 1976 and 2000 were
      analysed. Local and distant failure rates were calculated using the actuarial
      method and multivariable analysis was performed using a Cox model. RESULTS: The 5
      year cumulative rate was 12.8 percent for local recurrence and 25.6 percent for
      distant metastases. Five-year cumulative local recurrence rates were 4.9 percent
      for stage I, 11.0 percent for stage II and 23.5 percent for stage III tumours
      (P<0.001). The corresponding rates for distant metastases were 6.4, 21.4 and 48.0
      percent (P<0.001). The 5-year cumulative rates for distant metastases were 31.7
      percent for the period 1976-1980 and 21.1 percent for 1996-2000, and the local
      recurrence rates were 17.6 and 9.0 percent respectively. The decreases in rates
      of local recurrence and distant metastases were significant in multivariable
      analysis. Cancer extension and presenting features were related to patterns of
      failure. Tumour location was significantly associated with risk of local
      recurrence, whereas age and gross features were associated with risk of distant
      metastasis. CONCLUSION: Recurrence following resection of colonic cancer remains
      a substantial problem. Follow-up is of particular importance in the 3 years after
      surgery.

PMID- 16804871
TI  - Decreased levels of mucosal detoxification enzymes in the pouch of patients with
      familial adenomatous polyposis.
AB  - BACKGROUND: Adenomas can develop in the pouch after colectomy with ileal pouch
      anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP).
      Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST
      activity is much higher in the ileum than in the colon. The present study
      examined the hypothesis that the protective capacity of GSTs may be lowered as a
      result of colonic metaplasia of the ileal pouch. METHODS: Levels of GSTs,
      glutathione and cysteine, and the degree of inflammation and colonic metaplasia
      were quantified in biopsies from the pouch and afferent loop of 26 patients with
      FAP. RESULTS: GST enzyme activity, and levels of GST alpha, glutathione and
      cysteine in the pouch were significantly lower than those in the afferent loop
      (308 versus 398 nmol per min per mg protein (P<0.001), 4604 versus 5286 ng per mg
      protein (P=0.010), 27.1 versus 34.8 nmol per mg protein (P=0.023) and 0 versus
      4.8 nmol per mg protein (P=0.009) respectively). No correlation was found between
      inflammation or colonic metaplasia of the pouch and GST enzyme activity in the
      pouch. CONCLUSION: After IPAA, GST detoxification activity in the pouch is
      significantly lower than that in the afferent ileal loop, which may promote
      tumorigenesis.

PMID- 16804872
TI  - A meta-analysis comparing suprapubic and transurethral catheterization for
      bladder drainage after abdominal surgery.
AB  - BACKGROUND: Although bladder drainage is widely used for general surgical
      patients undergoing laparotomy, there is little consensus on whether suprapubic
      or transurethral catheterization is better. METHOD: A systematic database search
      was undertaken to find all studies of suprapubic catheterization. Randomized
      controlled trials were identified for inclusion. Endpoints for analysis were
      bacteriuria, patient satisfaction and recatheterization rates. A meta-analysis
      was performed using fixed-effect or random-effect models as appropriate,
      depending on heterogeneity. RESULTS: After abdominal surgery, transurethral
      catheterization is associated with significant bacteriuria (relative risk
      (RR)=2.02, P<0.001, 95 percent confidence interval (c.i.) 1.34 to 3.04) and pain
      or discomfort (RR=2.94, P=0.004, 95 percent c.i. 1.41 to 6.14). Recatheterization
      rates using the transurethral method were not increased significantly (RR=1.97,
      P=0.213, 95 percent c.i. 0.68 to 5.74) with heterogeneity between studies.
      CONCLUSION: The suprapubic route for bladder drainage in general surgery is more
      acceptable to patients and reduces microbiological morbidity.

PMID- 16804873
TI  - Nutrition and management of enterocutaneous fistula.
AB  - BACKGROUND: The management of enterocutaneous fistula is challenging, with
      significant associated morbidity and mortality. This article reviews treatment,
      with emphasis on the provision and optimal route of nutritional support. METHODS:
      Relevant articles were identified using Medline searches. Secondary articles were
      identified from the reference lists of key papers. RESULTS AND CONCLUSION:
      Management of enterocutaneous fistula should initially concentrate on correction
      of fluid and electrolyte imbalances, drainage of collections, treatment of sepsis
      and control of fistula output. The routine use of somatostatin infusion and
      somatostatin analogues remains controversial; although there are data suggesting
      reduced time to fistula closure, there is little evidence of increased
      probability of spontaneous closure. Malnutrition is common and adequate
      nutritional provision is essential, enteral where possible, although supplemental
      parenteral nutrition is often required for high-output small bowel fistulas. The
      role of immunonutrition is unknown. Surgical repair should be attempted when
      spontaneous fistula closure does not occur, but it should be delayed for at least
      3 months.

PMID- 16804874
TI  - Redefining the R1 resection in pancreatic cancer.
AB  - BACKGROUND: Resection margin (RM) status in pancreatic head adenocarcinoma is
      assessed histologically, but pathological examination is not standardized. The
      aim of this study was to assess the influence of standardized pathological
      examination on the reporting of RM status. METHODS: A standardized protocol (SP)
      for pancreaticoduodenectomy specimen examination, involving multicolour margin
      staining, axial slicing and extensive tissue sampling, was developed. R1
      resection was defined as tumour within 1 mm of the RM. A prospective series
      reported according to this protocol (SP series, n = 54) was compared with a
      historical matched series in which a non-standardized protocol was used (NSP
      series, n = 48). RESULTS: Implementation of the SP resulted in a higher R1 rate
      overall, and for pancreatic (22 of 26 85 per cent) compared with ampullary (four
      of 15) and bile duct (six of 13) cancer. Sampling of the circumferential RM was
      more extensive in the SP series and correlated with RM status. RM involvement was
      often multifocal (14 of 32), affecting the posterior RM most frequently (21 of
      32). Survival correlated with RM status for the entire SP series (P < 0.001), but
      not for the NSP series. There was a trend towards better median and actuarial 5
      year survival after R0 resection in the SP pancreatic cancer subgroup.
      CONCLUSION: Standardized examination influences the reporting of RM status.

PMID- 16804875
TI  - Study of neonatal exposure to androgenic endocrine disruptors, testosterone and
      dihydrotestosterone by normal-phase HPLC.
AB  - Neonatal exposure to androgen induces developmental abnormalities in the male
      reproductive system. To investigate whether neonatal exposure affects
      spermatogenesis in juvenile and pubertal testis, Sprague-Dawley rat pups were
      given androgen or various androgenic endocrine disruptors by a single injection
      on the day of birth at concentrations ranging between 4 mm to 200 mm, and
      sacrificed on day 21 (juvenile) or 50 (puberty). The testes were weighed and
      examined histologically at each stage. Further, the metabolites of
      steroidogenesis were analyzed using normal-phase high-performance liquid
      chromatography. Neonatal exposure significantly reduced testis weights and
      steroidogenesis of juveniles. Neonatal exposure to testosterone and
      dihydrotestosterone still suppressed pubertal steroidogenesis, although testis
      weight was completely restored during puberty.

PMID- 16804876
TI  - Particle beam radiotherapy for head and neck tumors: radiobiological basis and
      clinical experience.
AB  - BACKGROUND: Head and neck tumors are often located near critical organs, making
      it impossible to deliver a dose of conventional radiotherapy high enough to
      eradicate the disease. Our aim was to review the potential benefits and available
      clinical experience of particle beam therapy (hadrontherapy) in the treatment of
      these tumors. METHODS: A review of the literature was carried out through a
      MEDLINE search (publications between 1980 and 2005). RESULTS: A review of the
      available clinical data shows that particle beam therapy can offer several
      radiobiological and physical advantages over conventional photon radiotherapy:
      improved dose distribution permits dose escalation within the target and optimal
      sparing of normal tissue. Preclinical and clinical studies suggest that there may
      be benefits to using hadrontherapy for tumors characterized by poor
      radiosensitivity and critical location. At present, the most used hadrons are
      protons and, as yet on an experimental basis, carbon ions. It is now well
      accepted that there are certain indications for using proton therapy for skull
      base tumors (chordoma and chondrosarcoma), paranasal sinus carcinomas, selected
      nasopharyngeal tumors, and neutron/ion therapy for salivary gland carcinomas (in
      particular, adenoid cystic tumors). Its viability in other cases, such as locally
      advanced squamous cell carcinoma, melanoma, soft tissue sarcoma, and bone
      sarcoma, is still under investigation. CONCLUSIONS: Hadrontherapy can be
      beneficial in the treatment of tumors characterized by poor radiosensitivity and
      critical location. Further clinical and radiobiological studies are warranted for
      improved selection of patient population.

PMID- 16804877
TI  - Randomized phase II study of carboplatin/gemcitabine versus
      vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer: West
      Japan Thoracic Oncology Group (WJTOG) 0104.
AB  - BACKGROUND: Combined gemcitabine and carboplatin (GC) and combined gemcitabine
      and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for
      patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a
      randomized Phase II study of GC versus GV to compare them in terms of efficacy
      and toxicity. METHODS: One hundred twenty-eight patients with Stage IIIB or IV
      NSCLC were randomized to receive either carboplatin at an area under the curve of
      5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients)
      or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n =
      64 patients) every 3 weeks. RESULTS: Response rates were 20.3% for the GC
      patients and 21.0% for the GV patients. In the GC arm, the median survival was
      432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median
      survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The
      median progression-free survival was 165 days in the GC arm and 137 days in the
      GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in
      the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence
      of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3%
      vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity
      (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P =
      .057). CONCLUSIONS: Although the GV and GC regimens had different toxicity
      profiles, there was no significant difference in survival among patients with
      NSCLC in the current study.

PMID- 16804878
TI  - Induction of meiotic maturation in mouse oocytes by adenosine analogs.
AB  - In this study we have examined the meiosis-inducing influence of adenosine
      analogs in mouse oocytes. When a varied group of nucleosides and nucleotides were
      tested on overnight cultures of hypoxanthine-arrested, cumulus cell-enclosed
      oocytes (CEO), halogenated adenosine nucleosides, but not native adenosine,
      exhibited a significant meiosis-inducing capability. When tested under a variety
      of conditions, meiotic induction by 8-bromo-adenosine (8-Br-Ado) and a second
      adenosine analog, methylmercaptopurine riboside (MMPR), was especially potent in
      denuded oocytes (DO) compared to CEO and was not dependent on the type of
      inhibitor chosen to maintain meiotic arrest. Germinal vesicle breakdown (GVB) was
      stimulated with rapid kinetics and was preceded by an increase in AMP-activated
      protein kinase (AMPK) activity. Moreover, compound C, an inhibitor of AMPK,
      blocked the meiosis-inducing activities of both adenosine analogs. When tested
      for an effect on meiotic progression to metaphase II (MII) in spontaneously
      maturing CEO, 8-Br-Ado and the AMPK activator, 5-aminoimidazole-4-carboxamide 1
      beta-D-ribofuranoside (AICAR), increased the percentage of MII-stage oocytes, but
      MMPR decreased this number. Adenosine and inhibitors of de novo purine synthesis
      had no effect on the completion of maturation, while compound C suppressed this
      process. These results support the proposition that oocyte AMPK mediates the
      positive influence of AICAR and 8-Br-Ado on both the initiation and completion of
      meiotic maturation. The role of AMPK in MMPR action is less clear.

PMID- 16804879
TI  - Hexose-specificity of hexokinase and ADP-dependence of pyruvate kinase play
      important roles in the control of monosaccharide utilization in freshly diluted
      boar spermatozoa.
AB  - Incubation of boar sperm from fresh ejaculates in a minimal medium with 10 mM
      glucose induced a fast and intense activation of glycolysis, as indicated by the
      observed increases in the intracellular levels of glucose 6-phosphate (G 6-P) and
      ATP and the rate of formation of extracellular L-lactate. The effect of glucose
      was much more intense than that induced by fructose, sorbitol, and mannose. The
      greater utilization of glucose was related to a much greater sensitivity to
      hexokinase when compared with the other monosaccharides. Thus, the presence of
      0.5 mM glucose induced total hexokinase activity in supernatants from sperm
      extracts of 1.7 +/- 0.1 mIU/mg protein, while the same concentration of both
      fructose, mannose, and sorbitol induced total hexokinase activity from 0.3 +/-
      0.1 mIU/mg protein to 0.60 +/- 1 mIU/mg protein. Kinetic analysis of the total
      pyruvate kinase activity indicated that this activity was greatly dependent on
      the presence of ADP and also showed a great affinity for PEP, with an estimated
      Km in supernatants of 0.15-0.20 mM. Immunological location of proteins closely
      related to glycolysis, like GLUT-3 hexose transporter and hexokinase-I, indicated
      that these proteins showed the trend to be distributed around or in the cellular
      membranes of both head and midpiece in a grouped manner. We conclude that
      glycolysis is regulated by both the specific availability of a concrete sugar and
      the internal equilibrium between ATP and ADP levels. Furthermore, localization of
      proteins involved in the control of monosaccharide uptake and phosphorylation
      suggests that glycolysis starts at concrete points in the boar-sperm surface.

PMID- 16804880
TI  - Molecular cloning and characterization of SRG-L, a novel mouse gene
      developmentally expressed in spermatogenic cells.
AB  - Full-length cDNA of a novel mouse gene upregulated in late stages of
      spermatogenic cells was cloned from mouse testis using overlapping RT-PCR and
      RACE. The mRNA of the gene was expressed mainly in diplotene/pachytene
      spermatocytes, round and elongating spermatids. We named this gene as SRG-L
      (Spermatogenesis Related Gene expressed in late stages of spermatogenic cells,
      GenBank Accession No. AY352586). The tissue-specific analysis showed a higher
      expression level in testis and spleen. The gene is mapped on chromosome 8q33.1
      and contains 18 exons. The full-length of cDNA is 2,843 bp with an open reading
      frame (ORF) of 2,625 bp that encodes a 104 kDa protein (874 amino acids) with a
      putative transmembrane region. The bioinformatics analysis revealed that the SRG
      L has two conserved regions, transglutaminase-like homologues domain and D-serine
      dehydratase domain, rich phosphorylation sites and methylation sites. The SRG-L
      protein was detected in diplotene/pachytene spermatocytes and spermatids by
      immunohistochemical staining and Western blot. The results suggest that SRG-L may
      play definite roles regulating differentiation of germ cells during
      spermatogenesis, particularly during meiosis and spermiogenesis.

PMID- 16804881
TI  - A potential role for triglyceride as an energy source during bovine oocyte
      maturation and early embryo development.
AB  - The potential role of endogenous triglyceride in bovine oocyte maturation and
      preimplantation development has been investigated. Bovine immature oocytes were
      recovered from abattoir-derived ovaries, matured and fertilised in vitro and the
      zygotes grown to the blastocyst stage in SOFaaBSA. Methyl palmoxirate (MP) blocks
      the oxidation of fatty acids by inhibiting mitochondrial carnitine
      palmitoyltransferase A. The development of zygotes exposed to MP during oocyte
      maturation, and of zygotes exposed to MP during embryo culture has been assessed
      in terms of oxygen consumption by oocytes and embryos during a 4-6 hr incubation
      period in the presence of MP and as blastocyst formation and cell number.
      Immature oocytes exposed to MP during maturation had reduced capacity to form
      blastocysts after fertilisation; the same effect was apparent, but to a lesser
      extent, in zygotes exposed to MP during embryo development. Oxygen consumption
      values of oocytes and blastocysts in the absence of exogenous substrates were
      similar to those in control medium containing nutrients. MP-inhibited oxygen
      consumption of immature oocytes, mature oocytes, cleavage stages embryos and
      blastocysts by 64, 45, 12 and 13%, respectively. The data are consistent with a
      role for triglyceride as a key energy source during bovine oocyte maturation and
      potentially, during preimplantation embryo development.

PMID- 16804882
TI  - Suppression of endogenous estrogen during development affects porcine epididymal
      sperm maturation.
AB  - Estrogen plays an important role in male reproduction, critical for sustained
      fertility in some species. Reducing estrogen's interaction with its receptor(s)
      in monkey and mouse models is associated with reduced sperm motility and, in some
      cases, documented elimination of sperm fertilizing ability, suggesting that
      normal epididymal function may be estrogen dependent. The objective of these
      experiments was to evaluate the effects of reduced endogenous estrogen on
      development of epididymal function in the pig, a species in which males have very
      high levels of endogenous estrogen. Letrozole, a potent inhibitor of estrogen
      synthesis, was administered to neonatal boars from 1 week of age and markedly
      suppressed estrogen production. Epididymal function assessed as acquisition of
      sperm fertilizing ability (in vitro fertilization of zona-free oocytes) was
      reduced in Letrozole-treated animals at 24 and 28 weeks of age (23% and 30%
      fertilization, respectively compared with 37% and 54% in vehicle controls) but
      had recovered by 32 weeks of age. Cauda epididymal sperm numbers were reduced in
      treated animals (35% of control values at 20 weeks of age) but appeared to be
      recovering at 32 weeks of age. Reduction of endogenous estrogen had no effect on
      other aspects of epididymal function (percentage of motile sperm, sperm motion
      parameters, sperm head morphometrics, or ability of sperm to undergo an acrosome
      reaction). Reducing endogenous estrogen during postnatal development appears to
      have transient effects on porcine epididymal function. These transient effects
      suggest that the pig, with its high endogenous estrogen, may respond differently
      than other species to reduced estrogen synthesis.

PMID- 16804883
TI  - Adenylyl cyclases in oocyte maturation: a characterization of AC isoforms in
      bovine cumulus cells.
AB  - Mammalian oocytes are arrested at the G(2)/M transition in the meiotic cell
      cycle. It is well known that a decrease in intraoocyte cAMP concentrations
      accompanies resumption of meiosis, but the precise trigger of this decrease
      remains a mystery. Follicular somatic cells are intimately coupled to the oocyte
      and are thought to transmit maturation signals to the oocyte in response to
      hormonal stimulation. Here, we investigate the nature of the follicular somatic
      cell response to hormonal stimulation by identifying and characterizing the
      adenylate cyclase isoforms present in bovine cumulus cells. RT-PCR and Western
      blot analysis revealed the presence of multiple adenylyl cyclase isoforms in
      bovine granulosa and cumulus cells. Pharmacological manipulation of the AC
      isoforms showed that multiple isoforms were indeed active. Our data indicate that
      the PKC inhibited adenylate cyclases IV and VI and the calcium-stimulated isoform
      I predominate in bovine cumulus cells.

PMID- 16804884
TI  - Hyperactivation of monkey spermatozoa is triggered by Ca2+ and completed by cAMP.
AB  - Digital image analysis of the flagellar movements of cynomolgus macaque
      spermatozoa hyperactivated by caffeine and cAMP was carried out to understand the
      change in flagellar movements during hyperactivation. The degree of flagellar
      bending increased remarkably after hyperactivation, especially at the base of the
      midpiece. Mainly two beating patterns were seen in the hyperactivated monkey
      sperm flagella: remarkably asymmetrical flagellar bends of large amplitude and
      relatively symmetrical flagellar bends of large amplitude. The asymmetrical bends
      were often seen in the early stage of hyperactivation, whereas the symmetrical
      bends executed nonprogressive, figure-of-eight movement. Beat frequency of the
      hyperactivated spermatozoa significantly decreased while wavelength of flagellar
      waves roughly doubled. To determine the conditions under which the axonemes of
      hyperactivated sperm flagella have asymmetrical or symmetrical bends, the plasma
      membranes of monkey spermatozoa were extracted with Triton X-100 and motility was
      reactivated with MgATP(2-) under various conditions. The asymmetrical flagellar
      bends were brought about by Ca(2+), whereas the symmetrical flagellar bends
      resulted from low levels of Ca(2+) and high levels of cAMP. Under these
      conditions, beat frequency and wavelength of flagellar waves of demembranated,
      reactivated spermatozoa were similar to those of the hyperactivated spermatozoa.
      These results suggest that during hyperactivation of monkey spermatozoa
      intracellular Ca(2+) concentrations first rise, and then decrease while cAMP
      concentrations increase simultaneously.

PMID- 16804885
TI  - Expression of genes associated with allantois emergence in ovine and bovine
      conceptuses.
AB  - In the development of ruminant embryos, the emergence and growth of the allantois
      is critical for the establishment of the chorioallantoic placenta. The allantoic
      membrane contributes to all the vasculature that perfuses the placental tissues
      and the fetal membranes. Using suppressive subtractive hybridization to compare
      mRNA from Day 13 ovine preimplantation conceptuses (prior to allantoic emergence)
      with Day 17 allantoic membrane, we identified nine genes whose expression was
      associated with the emergence of the allantoic sac. Collagen alpha 1 type XII,
      collagen alpha 2 type I, collagen alpha 2 type V, epsilon 4 beta-globin,
      osteonectin, and uroplakin were expressed at significantly greater levels in
      ovine Day 17 allantois compared to Day 13 conceptuses. These genes are associated
      with the extracellular matrix and most likely are involved in establishing and
      strengthening the structural integrity of the allantoic sac and in the
      development of the blood vessels. RalB expression increased with development
      although at significantly greater levels in the allantois only at Day 19. Hoxa-10
      and RhoA showed no differential expression during this period. All these genes
      showed a similar temporal pattern of expression in bovine conceptuses at
      equivalent stages of development with significantly greater expression of all
      these genes, except for Hoxa-10, found in Day 24 allantois compared to Day 14
      conceptuses. This suggests that the role they play in allantoic emergence, growth
      and function is conserved in both ruminant species and that their expression is
      regulated in a similar manner. The interactions and regulation of this process
      remains to be fully explained.

PMID- 16804886
TI  - Human laminin-5 and laminin-10 mediated gene expression of prostate carcinoma
      cells.
AB  - In prostate cancer progression, the basal lamina switches from predominantly
      laminin-5 to laminin-10. DU-145 prostate cancer cells were treated with either
      soluble laminin-5 (20 ng/ml) or laminin-10 (1 microg/ml) for 6, 24, and 48 hr.
      Total RNA was harvested for a 7,500 human cDNA microarray. Hybridizations were
      carried out in accordance with a 10 sample analysis of variance (ANOVA)
      statistical model. One thousand one hundred sixteen genes had measurable
      expression 2 standard deviations above background and 50% of spots for any given
      sample for all hybridizations were positive. Expression values of significantly
      varying genes were clustered and a list of 408 genes (P < 0.05) with a 1.5 or
      greater fold change in at least one time point were chosen for further analysis.
      Seventy eight changed in a time-dependent manner with laminin-10 treatment, 85
      changed with laminin-5, and 13 showed changes with both treatments. The 408 genes
      that passed a paired t-test in at least one time-dependent category were further
      analyzed using Pathway Miner. One of the largest gene association networks
      involved signal transduction in the growth factor-MAP kinase pathways. EGFR was
      validated by real-time PCR and laminin-10 mediated cell adhesion activated EGFR
      in DU-145 cells. Both laminins appear to be important signal transducers in
      prostate cancer.

PMID- 16804887
TI  - Distinguishing Costello versus cardio-facio-cutaneous syndrome: BRAF mutations in
      patients with a Costello phenotype.

PMID- 16804888
TI  - Effects of cord motion on diffusion imaging of the spinal cord.
AB  - Measurement of diffusion and its dependence on direction has become an important
      tool for clinical and research studies of the brain. Diffusion imaging of the
      spinal cord may likewise prove useful as an indicator of tissue damage and axonal
      integrity; however, it is more challenging to perform diffusion imaging in the
      cord than in the brain. Here we report a study of the effects of motion on single
      shot fast spin echo (FSE) diffusion tensor imaging (DTI) of the spinal cord.
      Diffusion imaging was performed at four different times in the cardiac cycle both
      without and with velocity compensation of the diffusion gradients. Uncompensated
      diffusion images demonstrated substantial signal loss artifacts in the cord that
      were strongly dependent on the delay after the pulse-oximeter trigger.
      Quantitative diffusion analysis was also strongly affected by this motion
      artifact. The use of flow-compensated gradients helped to restore normal signal
      in the cord, especially at particular trigger delays. Theoretical arguments
      suggest that improved spatial resolution may help eliminate this signal loss.
      Even with higher spatial resolution, motion-related signal attenuation may still
      occur in diffusion imaging of pathologies that alter the motion of the cord.
      However, this same cord motion may contain diagnostically valuable information
      when probed using appropriate diffusion imaging approaches.

PMID- 16804889
TI  - High-resolution imaging of the intracranial arterial and venous systems following
      a single contrast injection.
AB  - PURPOSE: To generate two separate three-dimensional (3D) high spatial resolution
      images of the intracranial arterial and venous systems using a single contrast
      injection. MATERIALS AND METHODS: A 3D contrast-enhanced (CE) magnetic resonance
      angiography (MRA) acquisition was modified to create two separate k-space data
      sets to encode the arterial and venous enhancement signals individually after
      contrast agent injection. Following an automated detection of contrast arrival,
      the central k-space views corresponding to the arterial phase were acquired for
      the first eight seconds. A full elliptical-centric acquisition was then acquired
      for the venous phase and the missing views in the periphery of the first k-space
      data set were copied from the venous phase. A total of 18 patients underwent this
      study. Image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio
      (CNR) were determined in both intracranial systems. RESULTS: Two 3D image sets
      were generated for the arterial and venous intracranial systems. Both sets have
      high quality images that are clinically diagnostic. SNR and CNR were high in both
      sets, so that all the major vessels were visible. CONCLUSION: This technique
      provides images with high spatial resolution for both arterial and venous
      intracranial systems using a single contrast injection.

PMID- 16804891
TI  - Bladder tissue formation from cultured bladder urothelium.
AB  - Tissue recombination is a powerful method to evaluate the paracrine-signaling
      events that orchestrate the development of organs using the in vivo environment
      of a host rodent. Studies have reported the successful generation of primary
      cultures of rodent bladder urothelium, but none have reported their use to
      recapitulate bladder tissue with tissue recombination. We propose that primary
      cultured bladder urothelium, when recombined with inductive embryonic bladder
      mesenchyme, will form bladder tissue in a recombination model. Adult rat bladders
      were isolated and urothelium obtained. Sheets of bladder urothelium were re
      suspended in collagen and maintained in tissue culture. After expansion (>20
      passages), the urothelium was recombined with embryonic day-14 mouse bladder
      mesenchyme, then grafted beneath the renal capsule of immunocompromised mouse
      hosts. Grafts were harvested after 28 days. Control grafts were performed with
      bladder mesenchyme alone, cultured bladder urothelium alone, and collagen matrix
      alone. Final tissues were evaluated with staining and immunohistochemistry (H&E,
      Gomori's trichrome, broad-spectrum uroplakin, and smooth muscle actin alpha and
      gamma). Immunocytochemistry on cultured urothelium for broad-spectrum keratin,
      vimentin, and broad-spectrum uroplakin confirmed pure populations, void of
      mesenchymal contaminants. Staining of recombinant grafts demonstrated bladder
      tissue with mature urothelium and stromal differentiation. Control tissues were
      void of bladder tissue formation. We have successfully demonstrated that a
      chimeric bladder is formed from primary cultured bladder urothelium recombined
      with embryonic bladder mesenchyme. This is a powerful new tool for investigating
      the molecular mechanisms of bladder development and disease. Future applications
      may include the in vitro genetic manipulation of urothelium and examining those
      effects on growth and development in an in vivo environment.

PMID- 16804890
TI  - Selective assembly of fibulin-1 splice variants reveals distinct extracellular
      matrix networks and novel functions for perlecan/UNC-52 splice variants.
AB  - Fibulin-1C and fibulin-1D splice variants have been conserved throughout metazoan
      evolution and have distinct functions in Caenorhabditis elegans development. Both
      splice variants are required for the assembly of hemidesmosome-mediated
      mechanosensory neuron and uterine attachments, although the molecular
      associations that underlie their distinct functions at these locations are not
      known. Here, we show that the assembly of fibulin-1C and fibulin-1D splice
      variants at these anchorages is dependent upon distinct components of the
      extracellular matrix (ECM): Fibulin-1D assembly at uterine and mechanosensory
      neurons attachments is dependent upon a perlecan/ UNC-52 splice variant that
      includes alternately spliced IG8-IG10, whereas the assembly of fibulin-1C at
      mechanosensory neuron attachments is dependent upon laminin/ EPI-1. These data
      not only indicate that fibulin-1C and fibulin-1D are components of distinct
      networks of ECM but also demonstrates a novel function for a major class of
      perlecan splice variants found in C. elegans and mouse. In addition, we
      demonstrate that overexpression of another ECM protein, collagen XVIII, can
      suppress gonad morphogenesis defects associated with loss of fibulin-1C,
      suggesting that some genetic defects that result in a weakened basement membrane
      can be compensated by overexpression of genes for ECM components that stabilize
      basement membranes.

PMID- 16804892
TI  - Sema3D and Sema7A have distinct expression patterns in chick embryonic
      development.
AB  - By RT-PCR, we isolated a partial cDNA clone for the chick Semaphorin7A (Sema7A)
      gene. We further analyzed its expression patterns and compared them with those of
      the Sema3D gene, in chick embryonic development. Sema3D and Sema7A appeared to be
      expressed in distinct cell populations. In mesoderm-derived structures, Sema7A
      expression was detected in the newly formed somites, whereas Sema3D expression
      was found in the notochord. In ectoderm-derived tissues, Sema3D is expressed
      broadly in the surface ectoderm, lens and nasal placodes. Sema3D is also
      expressed in the developing nervous system including diencephalon, dorsal neural
      tube, optical and otic vesicles. In the limb bud, Sema3D expression was found
      throughout the ectoderm excluding the apical ectoderm ridge (AER), where Sema7A
      is concentrated. Although both genes appeared to be expressed in the migrating
      neural crest cells, Sema3D expression is limited to neural crest cells migrating
      out of the midbrain/hindbrain regions, while Sema7A expression is widespread in
      both cranial and trunk neural crest cells.

PMID- 16804893
TI  - FGF-4 signaling is involved in mir-206 expression in developing somites of
      chicken embryos.
AB  - The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that
      regulate gene expression in metazoans. We have cloned short RNAs from chicken
      embryos and identified five new chicken miRNA genes. Genome analysis identified
      17 new chicken miRNA genes based on sequence homology to previously characterized
      mouse miRNAs. Developmental Northern blots of chick embryos showed increased
      accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem
      cell-specific mir-302, which was expressed at high levels at early stages and
      then declined. In situ analysis of mature miRNAs revealed the restricted
      expression of mir-124 in the central nervous system and of mir-206 in developing
      somites, in particular the developing myotome. In addition, we investigated how
      miR-206 expression is controlled during somite development using bead implants.
      These experiments demonstrate that fibroblast growth factor (FGF) -mediated
      signaling negatively regulates the initiation of mir-206 gene expression. This
      may be mediated through the effects of FGF on somite differentiation. These data
      provide the first demonstration that developmental signaling pathways affect
      miRNA expression. Thus far, miRNAs have not been studied extensively in chicken
      embryos, and our results show that this system can complement other model
      organisms to investigate the regulation of many other miRNAs.

PMID- 16804894
TI  - Transgenic Xenopus laevis strain expressing cre recombinase in muscle cells.
AB  - For reproducible analyses of gene function in Xenopus, the use of transgenic
      strains is a promising approach but has limitations when investigating factors
      interfering with development. Therefore, inducible systems are attractive
      alternatives, and a binary system based on recombinases is a most versatile
      approach. We have shown previously that Cre and FLP recombinases are active in
      Xenopus laevis and can induce a silent reporter gene in a corresponding reporter
      strain. Here, we describe the establishment of the transgenic Xenopus laevis
      strain A7 expressing Cre recombinase under the control of the muscle-specific
      cardiac actin promoter. Upon crossing to several distinct reporter strains, A7 is
      able to induce EYFP, DsRed2, or LacZ reporter genes in a muscle-specific manner.
      This first Cre-expressing strain allows conditional activation of any gene of
      interest in muscle cells and, thus, opens up the use of recombinases as a new
      experimental strategy in Xenopus.

PMID- 16804895
TI  - Early temporal-specific responses and differential sensitivity to lithium and Wnt
      3A exposure during heart development.
AB  - Members of both Wnt and bone morphogenetic protein (BMP) families of signaling
      molecules are important in heart development. We previously demonstrated that
      beta-catenin, a key downstream intermediary of the canonical Wnt signaling
      pathway, delineates the dorsal boundary of the cardiac compartments in an
      anteroposterior progression. We hypothesized the progression involves canonical
      Wnt signaling and reflects development of the primary body axis of the embryo. A
      similar anteroposterior signaling wave leading to cardiac cell specification
      involves inductive signaling by BMP-2 synthesized by the underlying endoderm in
      anterior bilateral regions. Any molecule that disrupts the normal balance of Wnt
      and BMP concentrations within the heart field may be expected to affect early
      heart development. The canonical Wnt signaling step mimicked by lithium involves
      inactivation of glycogen synthase kinase-3beta (GSK-3beta; Klein and Melton
      [1996] Proc. Natl. Acad. Sci. U. S. A. 93:8455-8459). We show that lithium, Wnt
      3A, and an inhibitor of GSK-3beta, SB415286, affect early heart development at
      the cardiac specification stages. We demonstrate that normal expression patterns
      of key signaling molecules as Notch-1 and Dkk-1 are altered in the anterior
      mesoderm within the heart fields by a one-time exposure to lithium, or by noggin
      inhibition of BMP, at Hamburger and Hamilton (HH) stage 3 during chick embryonic
      development. The severity of developmental defects is greatest with exposure to
      lithium or Wnt-3A at HH stage 3 and decreases at HH stage 4. Taken together, our
      results demonstrate that there are temporal-specific responses and differential
      sensitivities to lithium/Wnt-3A exposure during early heart development.

PMID- 16804896
TI  - Subpopulations of motor and sensory neurons respond differently to brain-derived
      neurotrophic factor depending on the presence of the skeletal muscle.
AB  - The aim of our study was to assess the ability of brain-derived neurotrophic
      factor (BDNF) to rescue motor and sensory neurons from programmed cell death. It
      is clearly demonstrated that the administration of a single injection of a
      putative neurotrophic factor to mouse embryos in utero on embryonic day (E) 14.5
      is sufficient to significantly reduce the death of motor neurons when assessed on
      E18.5. However, the trophic requirements of somatic neurons have not been
      unequivocally determined in a mammalian species in vivo. Indeed, the unexpectedly
      high numbers of surviving neurons observed in neurotrophin and tyrosine kinase
      receptor knockout mice are probably the consequence of functional redundancy
      between the neurotrophins and their receptors. We studied spinal cord and facial
      motor nucleus neurons and proprioceptive neurons in the dorsal root ganglion and
      mesencephalic nucleus. The action of BDNF was assessed in wild-type fetuses to
      gain insight into its ability to rescue neurons from naturally occurring
      programmed cell death. In addition, we used Myf5(-/-):MyoD(-/-) embryos, which
      completely lack skeletal musculature, to assess the ability of BDNF to rescue
      neurons from excessively occurring programmed cell death. We found that BDNF
      differentially rescued neurons from naturally vs. excessively occurring cell
      death and that its ability to do so varied among neuronal subpopulations.

PMID- 16804897
TI  - Nephritogenic anti-DNA antibodies regulate gene expression in MRL/lpr mouse
      glomerular mesangial cells.
AB  - OBJECTIVE: Lupus-associated IgG anti-double-stranded DNA antibodies are thought
      to be pathogenic in the kidney due to cross-reaction with glomerular antigens,
      leading subsequently to immune complex formation in situ and complement
      activation. We undertook this study to determine if pathogenic anti-DNA
      antibodies may also contribute to renal damage by directly influencing mesangial
      gene expression. METHODS: Complementary DNA microarray gene profiling was
      performed in primary mesangial cells (derived from lupus-prone MRL/lpr mice)
      treated with pathogenic, noncomplexed anti-DNA antibodies. Significant gene up
      regulation induced by anti-DNA antibodies as determined by microarray analysis
      was further investigated by real-time polymerase chain reaction and methods to
      detect the relevant proteins. Induction of proinflammatory genes by pathogenic
      antibodies was confirmed by comparing gene expression in glomeruli of old versus
      young MRL/lpr mice, and by antibody injection in vivo. RESULTS: Pathogenic, but
      not nonpathogenic, antibodies significantly induced a number of transcripts,
      including CXCL1/KC, LCN2, iNOS, CX3CL1/fractalkine, SERPINA3G, and IkappaBalpha
      ("marker genes"). Blocking of Fcgamma receptors or using Fcgamma chain-knockout
      mesangial cells had no effect on the gene regulation effect of the pathogenic
      antibody R4A, indicating a non-Fc-dependent mechanism. The glomerular expression
      of these marker genes increased over time with the development of glomerular
      antibody deposition and active nephritis in MRL/lpr mice. Moreover, injection of
      R4A into SCID mice in vivo significantly up-regulated glomerular marker gene
      expression. CONCLUSION: These findings indicate that the renal pathogenicity of
      anti-DNA antibodies may be attributed in part to their ability to directly
      modulate gene expression in kidney mesangial cells through both Fc-dependent and
      non-Fc-dependent mechanisms.

PMID- 16804898
TI  - Intrauterine environment and breast cancer risk in a population-based case
      control study in Poland.
AB  - High estrogen exposure in utero may increase breast cancer risk later in life.
      However, studies of the associations between perinatal factors presumed to affect
      the fetal hormonal environment and breast cancer risk are inconsistent. We used
      data from a population-based case-control study of 2,386 incident breast cancers
      and 2,502 controls in Poland to evaluate risks associated with various perinatal
      characteristics. After adjusting for confounders, we found a significant trend (p
      = 0.01) of breast cancer risk with birth weight (OR = 1.54, 95% CI 1.08-2.19 for
      birth weights >4,000 g vs. <2,500 g). Subjects with a high birth order (> or =6)
      were at reduced risk (OR = 0.81, 0.61-1.06) when compared with first born
      subjects. Birth weight was somewhat a stronger risk predictor among subjects
      whose cancers were diagnosed at 50 years of age or older (OR = 1.84, 1.19-2.85)
      than among those with cancers diagnosed at younger ages (OR = 1.14, 0.61-2.12).
      Subjects whose mothers smoked during their pregnancies were at slightly higher
      risk than those who never smoked (OR = 1.21, 0.99-1.47), but the risk was similar
      to mothers who only smoked at other times (OR = 1.22, 0.81-1.84). Breast cancer
      risk was not related to paternal smoking, maternal age, gestational age or twin
      status. Our results add support to the growing evidence that some perinatal
      exposures may relate to breast cancer risk. Additional studies are needed to
      confirm associations and clarify the biologic mechanisms underlying these
      associations.

PMID- 16804899
TI  - Transcriptional profiling endometrial carcinomas microdissected from DES-treated
      mice identifies changes in gene expression associated with estrogenic tumor
      promotion.
AB  - Exposure to unopposed estrogen is a potent risk factor for developing human
      endometrial cancer. However, little is known about the transcriptional changes
      elicited by estrogens in endometrial carcinogenesis, in part, because of genetic
      and environmental heterogeneity of human tumors. We have begun to chart the
      expression signatures of endometrial tumors promoted with the synthetic estrogen,
      diethylstilbestrol (DES), in inbred mice. As expected, laser-capture
      microdissected endometrial cancers from DES-treated mice displayed a large number
      of transcriptional changes when compared to uninvolved endometrial epithelium.
      Genes differentially expressed in carcinomas included cell adhesion and
      extracellular matrix genes (Decorin as 1 example), developmental genes (Hoxa11),
      and cytokine signaling genes (Socs3). The DES-promoted carcinomas appeared to
      fall into 2 distinct transcriptional classes, and expression of the tumor
      suppressor Pten was among the top discriminators between the 2 cancer groups.
      Pten was down regulated in the majority of the DES-promoted carcinomas, which is
      analogous to the frequent loss of PTEN expression in human endometrial tumors.
      Although preliminary, these observations suggest that the cancers that arise in
      the DES model bear similarities to human endometrial cancers and provide insights
      into transcriptional alterations that accompany estrogen-driven endometrial
      carcinogenesis.

PMID- 16804900
TI  - Severe oxidatively damaged DNA after cisplatin treatment of cancer patients.
AB  - There is growing evidence suggesting that cytotoxic activity of cisplatin is
      closely associated with increased generation of reactive oxygen species (ROS).
      Therefore, this study was undertaken to examine oxidative DNA damage, which
      arises as a result of chemotherapy with cisplatin. Using HPLC
      prepurification/isotope dilution GC/MS methodology, we examined the amount of 8
      oxoGua and 8-oxodG excreted into urine in cancer patients (n = 66) who received
      chemotherapy with cisplatin. One day after the infusion of the drug, significant
      increase in the amount of 8-oxoGua and 8-oxodG in urine of the patients was
      observed, when compared to the initial value (78%, p < 0.0001 and 22%, p =
      0.0051). In the "nadir days" (when the most distinct cell death based on
      hematological cell counts can be observed), the level of modified base and
      nucleoside decreased in comparison with the aforementioned time point. These
      results, for the first time, indicate that oxidatively damaged DNA may be, at
      least in part, responsible for cisplatin induced cytotoxicity. Our results also
      demonstrate that cell death does not contribute to urinary 8-oxoGua and 8-oxodG
      in humans.

PMID- 16804901
TI  - Variant genotypes of CDKN1A and CDKN1B are associated with an increased risk of
      breast cancer in Chinese women.
AB  - p21(Cip1) and p27(Kip1) are cyclin-dependent kinase inhibitors, which can arrest
      cell proliferation and serve as tumor suppressors. Reduced protein expression of
      p21(Cip1) and p27(Kip1) was frequently observed in a subset of cancers, including
      breast cancer. In this study, we hypothesized that genetic variants in CDKN1A
      (encode for p21(Cip1)) and CDKN1B (encode for p27(Kip1)) may modulate the risk of
      breast cancer. To test this hypothesis, we evaluated the associations of the
      polymorphisms of Ser31Arg and C+20T in CDKN1A and C-79T and Gly109Val in CDKN1B,
      as well as their combinations, with breast cancer risk in a case-control study of
      368 breast cancer cases and 467 cancer-free controls in a Chinese population. We
      found that a significantly increased risk of breast cancer was associated with
      the variant genotypes of CDKN1B C-79T [adjusted OR = 1.43 (95% CI = 1.03-1.98)
      for -79TC/TT], compared with the -79CC genotype, but no associations were
      observed for other variant genotypes. However, the combined variant genotypes of
      the 4 loci were associated with a significantly increased breast cancer risk
      (adjusted OR = 1.49, 95% CI = 1.11-2.01 among subjects carrying 3 or more variant
      alleles), especially among premenopausal women (adjusted OR= 2.30, 95% CI = 1.45
      3.66). Furthermore, in premenopausal women, this significant association remained
      unchanged, after including other individual risk factors in the multivariate
      logistic regression model, suggesting an independent role of CDKN1A and CDKN1B
      variants in breast cancer risk. Although the exact biological mechanism remains
      to be explored, our findings suggest possible involvement of CDKN1A and CDKN1B
      variants in the etiology of breast cancer. Further large and functional studies
      are needed to confirm our findings.

PMID- 16804902
TI  - The expression levels of the transcriptional regulators p300 and CtBP modulate
      the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human
      colon carcinomas.
AB  - ZEB1 and SNAIL repress CDH1 and induce epithelial-mesenchymal transition (EMT).
      However, SNAIL and ZEB1 also activate or regulate other target genes in different
      ways. For instance, vitamin D receptor (VDR), which activates CDH1 expression
      upon ligand binding, is repressed by SNAIL but induced by ZEB1. We examined
      whether the biological activity of SNAIL and ZEB1 in colon cancer is regulated by
      interacting cofactors. The mRNA expression levels of SNAIL and ZEB1, and of
      transcriptional regulators p300 and CtBP, were measured by RT-PCR in tumor and
      normal tissue from 101 colon carcinoma patients. Overexpression of SNAIL was
      associated with down-regulation of CDH1 and VDR (p = 0.004 and p < 0.001). CDH1
      correlated with VDR (r = 0.49; p < 0.001). ZEB1 expression also correlated with
      VDR (r = 0.23; p = 0.019). However, when CtBP was strongly expressed, ZEB1 was
      inversely correlated with CDH1 (r = -0.39; p = 0.053). Furthermore, when there
      were elevated p300 expression levels, the correlation between expression of ZEB1
      and VDR was stronger (r = 0.38; p = 0.070). Association between SNAIL expression
      and down-regulation of CDH1 and VDR was lost in tumors in which p300 and CtBP
      were strongly expressed. These results indicate that the levels of expression of
      CtBP and p300 are critical for the action of SNAIL and ZEB1, which have a pivotal
      role in EMT, and show the importance of CtBP and p300 for tumor progression.

PMID- 16804904
TI  - Prognostic significance of matrix metalloproteinase-7 in epithelial ovarian
      cancer and its relation to beta-catenin expression.
AB  - We investigated the expression and prognostic significance of matrix
      metalloproteinase (MMP) -7, its relation to beta-catenin expression and
      clinicopathological factors in epithelial ovarian cancer. The expression of MMP-7
      was analyzed immunohistochemically in a series of 284 primary epithelial ovarian
      cancers, their 36 metastases and 8 normal ovaries. In cancers with endometrioid
      histology, a high percentage area of MMP-7 expression and an intense MMP-7 signal
      was significantly associated with nuclear positivity of beta-catenin in cancer
      cells (p = 0.003, chi2 = 8.853 and p = 0.030, chi2 = 4.713, respectively). In all
      tumors and nonendometrioid subgroup, a low percentage area of MMP-7 positive
      tumor cells was significantly correlated with a high histological grade of the
      tumor (p = 0.003 and 0.005, respectively), in all tumors also with advanced stage
      of the tumor (p = 0.002) and large primary residual tumor (p = 0.005). A 10-year
      disease-related survival (DRS) was significantly better when the percentage area
      of MMP-7 expression in cancer cells was high, when compared to low (p = 0.0008).
      A high percentage area of intense MMP-7 signal in cancer cells predicted a
      significantly more favorable DRS and recurrence-free survival (RFS) (p = 0.0003
      and 0.0052, respectively). In multivariate analysis, a high percentage area of
      intense MMP-7 signal in tumor cells was an independent prognostic factor,
      predicting favorable DRS and RFS. The present study showed that intense MMP-7
      signal in tumor cells is an independent prognostic factor predicting better
      survival in epithelial ovarian cancer.

PMID- 16804905
TI  - Structure and function of the components of the human DNA mismatch repair system.
AB  - DNA mismatch repair (MMR) is one of the several enzyme systems involved in DNA
      homeostasis. DNA MMR is involved in the repair of specific types of errors that
      occur during new DNA synthesis; loss of this system leads to an accelerated
      accumulation of potential mutations, and predisposes to certain types of cancers.
      Germline mutations in some of the DNA MMR genes cause the hereditary cancer
      predisposition, Lynch syndrome. This review addresses advances in the
      biochemistry of DNA MMR and its relationship to carcinogenesis.

PMID- 16804906
TI  - M-CAM expression as marker of poor prognosis in epithelial ovarian cancer.
AB  - Currently available clinico-pathologic criteria provide an imperfect assessment
      of outcome for patients with advanced epithelial ovarian cancer (EOC).
      Identification of prognostic factors related to tumor biology might improve this
      assessment. We investigated the prognostic significance of the melanoma cell
      adhesion molecule (M-CAM) in EOC. Using the same antibody, M-CAM expression was
      tested by Western blotting in protein extracts and by immunohistochemestry in
      tissue microarrays generated from 133 consecutively resected, well characterized
      EOC samples. Fisher test, Kaplan-Meier method and Cox proportional hazards
      analysis were used to relate M-CAM expression to clinico-pathological variables
      and to time to progression (TTP) and overall survival (OS). In vitro biochemical
      analysis showed a progressively increased M-CAM expression from normal to
      malignant cells. M-CAM protein, detected immunohistochemically, was significantly
      associated with advanced tumor stage, serous and undifferentiated histotype,
      extent of residual disease and p53 accumulation. Presence or absence of M-CAM
      significantly divided patients according to their TTP (median, 22 vs. 79 months,
      respectively; log-rank p = 0.001) and OS (median, 42 vs. 131 months,
      respectively; log-rank p = 0.0003). In the subgroup of advanced stage patients
      who achieved complete response after front-line treatment, M-CAM expression and
      absence of residual disease were significantly associated with shorter TTP (p =
      0.003, HR 5.25, 95% Cl 1.79-15.41 and p = 0.011, HR 3.77, 95% Cl 1.36-10.49
      respectively) at the multivariate level. In the same sub-group of patients, M-CAM
      expression remained the only parameter significantly associated with OS (p =
      0.005, HR 3.35, 95% Cl 1.42-6.88). M-CAM is a marker of early relapse and poorer
      outcome in EOC. In particular, M-CAM expression identifies a subgroup of front
      line therapy-responding patients who undergo dramatic relapses, thus helping to
      better select patients who might benefit from new/alternative therapeutic
      modalities.

PMID- 16804907
TI  - Development of the tumor vascular bed in response to hypoxia-induced VEGF-A
      differs from that in tumors with constitutive VEGF-A expression.
AB  - Tumors arise initially as avascular masses in which central hypoxia induces
      expression of vascular endothelial growth factor-A (VEGF-A) and subsequently
      tumor vascularization. However, VEGF-A can also be constitutively expressed as a
      result of genetic events. VEGF-A is alternatively spliced to yield at least 6
      different isoforms. Of these, VEGF-A(121) is freely diffusible whereas basically
      charged domains in the larger isoforms confer affinity for cell surface or
      extracellular matrix components. We previously reported that in a mouse brain
      metastasis model of human melanoma, VEGF-A(121) induced a qualitatively different
      tumor vascular phenotype than VEGF-A(165) and VEGF-A(189): in contrast to the
      latter ones, and VEGF-A(121) did not induce a neovascular bed but rather led to
      leakage and dilatation of preexistent brain vessels. Here, we correlate vascular
      phenotypes with spatial VEGF-A expression profiles in clinical brain tumors (low
      grade gliomas; n = 6, melanoma metastases; n = 4, adenocarcinoma metastases; n =
      4, glioblastoma multiforme; n = 3, sarcoma metastasis; n = 1, renal cell
      carcinoma metastasis; n = 1). We show that tumors that constitutively express
      VEGF-A present with different vascular beds than tumors in which VEGF-A is
      expressed as a response to central hypoxia. This phenotypic difference is
      consistent with a model where in tumors with constitutive VEGF-A expression, all
      isoforms exert their effects on vasculature, resulting in a classical angiogenic
      phenotype. In tumors where only central parts express hypoxia-induced VEGF-A, the
      larger angiogenic isoforms are retained by extracellular matrix, leaving only
      freely diffusible VEGF-A(121) to exert its dilatation effects on distant vessels.

PMID- 16804908
TI  - Organophosphorus pesticide urinary metabolite levels of children in farmworker
      households in eastern North Carolina.
AB  - BACKGROUND: Organophosphorus (OP) pesticide urinary metabolite levels in a sample
      of farmworker children in North Carolina are documented and compared to national
      reference data. The relative importance of para-occupational, residential, and
      environment risk factors are delineated. METHODS: Urine samples were collected
      from 60 farmworker children 1-6 years of age, and interviews were completed by
      their mothers. Urine samples were analyzed for the dialkylphosphate (DAP)
      metabolites of OP pesticides. Summed molar concentrations of the diethyl and
      dimethyl DAP metabolites provided summary measures. RESULTS: The farmworker
      children had relatively high levels of OP pesticide urinary metabolites compared
      to national reference data; for example, participating children had higher
      geometric means for diethylphosphate (DEP), diethylthiophosphate (DETP), and the
      summed diethyl metabolites. However, analyses found no pattern of significant
      associations between predictors and metabolite levels. CONCLUSIONS: Future
      research requires greater precision in sampling and measurement to determine the
      risk factors for pesticide exposure among farmworker children.

PMID- 16804909
TI  - A computer system for coding occupation.
AB  - BACKGROUND: Occupation information is widely used in epidemiologic studies and is
      collected on most death certificates and many birth certificates in the United
      States. Coding the massive amount of occupation information collected has been a
      challenge. METHODS: A simple word-matching computer program to code occupation
      entries from vital records was developed. The accuracy of the program was
      evaluated by comparing its output to codes assigned by human coders. RESULTS: In
      routine use in the Washington State Department of Health (DOH), the computer
      system codes 96-97% of the occupation entries on birth and death records. It
      assigned the correct code on 89% (95% confidence interval (87%, 91%)) of the
      records it coded. CONCLUSIONS: The occupation-coding program is both efficient
      and accurate and can simplify the process of coding occupation entries from vital
      records. The system is adaptable and can be modified to use occupation
      classifications other than the one used by DOH.

PMID- 16804910
TI  - The Italian surveillance system for occupational cancers: characteristics,
      initial results, and future prospects.
AB  - BACKGROUND: Occupational cancer monitoring is important for cancer prevention and
      public health protection. A surveillance system for identifying occupational
      cancer risks and cancer cases in Italy that are likely to be of occupational
      origin using information available in the Italian Social Security archives was
      created and assessed. Persons employed in the private sector, the employing
      company, its industrial sector, and years of employment are available in these
      archives. METHODS: A method to find known occupational hazards was first tested
      using a case-control approach. Cases were from six Italian cancer registries
      (CRs) and controls were sampled from source populations and as "exposure" the
      economic sector of the employing company was used. The potential of using
      hospital discharge records as case sources was subsequently assessed: these cover
      larger populations and are available more quickly than CR case series. RESULTS:
      In the CR-based study many known occupational cancer risks related to specific
      industrial sectors were identified. By using cases from hospital discharge
      records many industries at risk were identified, as well as cases of recent
      diagnosis likely to be of occupational origin. However, for some industrial
      sectors (e.g., the chemical industry) the approach was unable to detect any
      excess risk. Furthermore, information on employees in important areas like
      agriculture, self-employment, and the public sector is not available in the
      Social Security archives. CONCLUSIONS: This approach appears to be a promising
      low-cost method for occupational cancer surveillance, at least for some
      industries, and can be easily implemented in other countries.

PMID- 16804911
TI  - Worker participation in change processes in a Danish industrial setting.
AB  - BACKGROUND: Improving the design, management and organization of work may be an
      important step in improving occupational health. An intervention, guided by the
      principles of participatory action research (PAR), is directed at traditional
      work environment problems in the epoxy plastic industry, that is, eczema and
      accident-related injuries. METHODS: The study population consisted of employees
      at two wind turbine- manufacturing plants. A quasi-experimental design was
      employed with before and after measurements and a comparison group with a 3(1/2)
      year follow-up period. RESULTS: The role of employee elected safety
      representatives was changed from one of controlling and "policing" to that of
      safety advisors. The attitudes of employees also changed, from an individualistic
      understanding of safety as the responsibility of the single employee, to a more
      collective understanding of safety as being everyone's shared responsibility.
      Structural changes led to a less hierarchical management system. This process led
      eventually to the establishment of self-governing work groups in which each
      member had a well-defined area of responsibility. The change process was
      associated with improvements in the psychosocial work environment and safety
      climate, a 66% reduction in the incidence of eczema, and a 48.6% reduction in the
      incidence of occupational accidents. In the comparison population, a twin factory
      under the same company, similar but delayed and less dramatic changes also
      occurred. CONCLUSIONS: Implementation of a comprehensive intervention was
      followed by improved employee perceptions of the company's safety standards and
      the psychosocial work environment, as well as by substantial reductions in the
      incidence of eczema and occupational accidents.

PMID- 16804912
TI  - Cancer morbidity in iron and steel workers in Korea.
AB  - BACKGROUND: In the iron and steel industry, workers are potentially exposed to a
      number of carcinogens and are involved in a number of processes of a hazardous
      nature. The cancer morbidity of iron and steel workers from modern plants in a
      developing country is described. METHODS: Cancer morbidity at two Korean iron and
      steel complexes was analyzed using Poisson regression methods. Work histories
      were merged with the national cancer registry for 44,974 workers who were
      followed from 1988-2001. RESULTS: Four hundred sixty-four cancers, in 1% of the
      population, were diagnosed over 14 years. Based on national cancer rates, the
      cohort exhibited a healthy worker effect for all cancer (SIR = 0.87, 95% CI =
      0.79-0.95) reflecting relative good health, particularly for lung cancer (SIR =
      0.58, 95% CI = 0. 04-0.82), stomach cancer (SIR = 0.78, 95% CI = 0.64-0.93), and
      liver cancer (SIR = 0.83, 95% CI = 0.68-1.01). Lung cancer morbidity was
      significantly elevated at the affiliated plants versus the parent plants (SRR =
      2.35, 95% CI = 1.07-4.92), and all-cancer morbidity was significantly elevated
      for maintenance workers compared to office and production workers (SRR = 1.27,
      95% CI = 1.00-1.60). Lymphohematopoietic cancer incidence was higher in the coke
      plants (SRR = 3.46, 95% CI = 1.02-8.91) and stomach cancer incidence was higher
      in the maintenance departments (SRR = 1.66, 95% CI = 1.05-2.56). CONCLUSIONS:
      This recent steelworker cohort exhibits possible excess cancer morbidity in some
      processing areas. Further follow-up of this cohort and alternate study designs
      such as case-control study will be needed to elucidate the relationship of
      exposure and health risks of iron and steel workers.

PMID- 16804916
TI  - Increased WSB1 copy number correlates with its over-expression which associates
      with increased survival in neuroblastoma.
AB  - Gain of chromosome 17 is the most prevalent genetic abnormality identified in
      neuroblastoma (NB) and distal 17q gain has prognostic significance in NB. In this
      report, we have combined array-based comparative genomic hybridization (A-CGH)
      and gene expression analysis to investigate gene copy number changes and its
      impact on the gene expression level as well as their association with prognosis
      genes located on chromosome 17 in NB tumors. We observed differential gains of
      chromosome 17 between Stages 4- and 4S tumors. We found that WSB1, mapping to
      17q11.1, which was frequently gained in 4S- tumors and not changed in 4- tumors,
      showed strong correlations between expression level and copy number. Furthermore,
      the increase of WSB1 gene expression is associated with good outcome in patients
      with NB of all stages. WSB1 also enhances the prognostic prediction when combined
      with other current prognostic factors in NB. Our results demonstrate that WSB1
      copy number correlates with its expression level and that its high expression
      associates with good prognosis suggesting a possible role of this gene in the
      biology of favorable outcome NB. This article contains Supplementary Material
      available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 16804915
TI  - Worker productivity and outpatient service use after the September 11th attacks:
      results from the New York City terrorism outcome study.
AB  - BACKGROUND: Research has shown that the terrorist attacks in New York City (NYC)
      on September 11, 2001 had an impact on the psychological status of area
      residents. Since a major goal of many terrorist attacks is to also adversely
      affect local socioeconomic activities, the long-term impact of exposure to
      terrorist attacks on productivity and outpatient service utilization among
      workers in NYC is assessed. METHODS: The impact of the World Trade Center
      disaster (WTCD) among 1,167 workers in NYC is examined using a prospective cohort
      design. The study included measures of WTCD exposures, stressful life events,
      other traumatic events, post-traumatic stress disorder (PTSD), and depression,
      assessed at 1 year and 2 years post-disaster. RESULTS: Bivariate analyses suggest
      that exposure to WTCD events is associated with high productivity loss at
      baseline, but not consistently at follow-up. Both PTSD and depression are
      associated with lower quality workdays at baseline and follow-up, but depression
      is more consistently associated with high work loss and medical service use. In
      multivariate analyses, WTCD exposure is associated with productivity loss at
      baseline, but less consistently at follow-up. At baseline, depression and history
      of traumatic events are associated with lower quality workdays and negative life
      events with greater workdays lost. Multivariate analyses at follow-up indicated
      that experiencing negative life events is associated with higher workdays lost
      and lower quality workdays and that PTSD is associated with lower quality
      workdays. Similar regression models suggested that increased outpatient service
      use is associated with depression and lifetime traumatic events at baseline and
      with negative life events at follow-up. CONCLUSION: This study suggests that
      while the WTCD had an impact on worker productivity within the first year after
      the attack, this did not generally persist, especially after controlling for
      baseline status. Having PTSD or experiencing stressful life events at follow-up,
      however, is associated with lower quality workdays, even after controlling for
      baseline status.

PMID- 16804917
TI  - A novel fusion of the MALT1 gene and the microtubule-associated protein 4 (MAP4)
      gene occurs in diffuse large B-cell lymphoma.
AB  - Rearrangements of the MALT1 gene by the t(11;18)(q21;q21) and t(14;18)(q32;q21)
      are the most frequent structural chromosomal abnormalities in MALT lymphomas.
      These translocations lead to fusions of BIRC3-MALT1 and IGH-MALT1 respectively,
      and activate the NF-kappaB pathway. Among 122 diffuse large B-cell lymphomas and
      28 Burkitt's lymphomas screened by interphase FISH, we found two cases with a
      break within MALT1, but without a t(11;18) or a t(14;18). Molecular genetic
      analyses in one of these cases revealed a novel "in frame" fusion of exon 9 of
      MALT1 and exon 9 of the microtubule-associated protein 4 (MAP4) gene. The
      translocation was accompanied by a deletion of MALT1 sequences distal to the
      breakpoint including the caspase-like domain, which is essential for activation
      of NF-kappaB. As a result of the deletion, the reciprocal 5'MAP4-3'MALT1
      transcript was not present, demonstrating that the 5'MALT1-3'MAP4 fusion
      represents the pathogenetically relevant transcript. Immunohistochemistry with
      amino-terminal and carboxy-terminal MALT1 antibodies, indicated a strong
      expression of the chimeric MALT1-MAP4 protein. Moreover, NF-kappaB activation was
      not increased in this case as shown by the levels of IkappaBalpha phosphorylation
      and NEMO ubiquitination. Our data demonstrate that the pathogenetic consequences
      of the novel MALT1-MAP4 fusion are different from those of the known MALT1
      associated chromosomal rearrangements and do not involve NF-kappaB activation.

PMID- 16804918
TI  - Contribution of the BOP1 gene, located on 8q24, to colorectal tumorigenesis.
AB  - The most common form of genomic instability observed in colorectal cancer is
      chromosomal instability (CIN), whose molecular bases remain to be determined. We
      have previously demonstrated that inactivation in human cells of several
      components of the Pes1-Bop1 complex (BOP1, GRWD1, PES1, ORC6L, and RPL3),
      involved in ribosome biogenesis, altered chromosome segregation. To determine the
      contribution to colorectal tumorigenesis of somatic alterations of genes involved
      in ribosome biogenesis, we screened 56 primary colorectal cancers, using
      quantitative multiplex PCR of short fluorescent fragments, a sensitive method for
      the detection of gene dosage alterations. We found that dosage increase of the
      BOP1 gene was a frequent event, being detected in 39% of the tumors, and we show
      that it is associated with an increase of BOP1 mRNA. Scanning of 8q24, on which
      BOP1 is located, revealed that in colorectal cancers, gene dosage increase of
      BOP1 can be independent from that of MYC and was more frequent than that
      affecting MYC. Finally, transient overexpression of BOP1 in human cells increased
      the percentage of multipolar spindles. Together with our previous results, the
      present study strongly suggests that deregulation of the BOP1 pathway contributes
      to colorectal tumorigenesis.

PMID- 16804919
TI  - Transforming potential of the T-cell acute lymphoblastic leukemia-associated
      homeobox genes HOXA13, TLX1, and TLX3.
AB  - The importance of HOXA genes in T-cell acute lymphoblastic leukemia (T-ALL) has
      recently been recognized. We report a novel chromosomal translocation in a T-ALL
      patient that maps upstream of the HOXA13 gene and downstream of the BCL11B/CTIP2
      locus. Analysis of HOXA gene transcription demonstrated massive expression of
      HOXA13, whereas the other HOXA genes were unaffected. A genomic rearrangement of
      the HOXA locus associated with exclusive expression of HOXA13 was observed in a
      second patient. This situation resembles chromosomal translocations activating
      genes of the TLX/HOX11 family in T-ALLs. To compare the leukemogenic properties
      of HOXA13 to that of TLX proteins, cohorts of lethally irradiated mice were
      transplanted with bone marrow transduced with a retroviral vector expressing TLX3
      or HOXA13. Cells transduced with TLX3 or HOXA13 could not be detected in the
      peripheral blood of mice post-transplantation and none of the mice developed
      malignancies. Cotransduction of the HOX cofactor MEIS1 with TLX3 or HOXA13 did
      not alter this outcome. However, in a myeloid clonogenic assay HOXA13 and TLX3
      extended the proliferation of progenitors similarly to what was observed for
      TLX1. Altogether, our results strongly suggest the absolute requirement for
      cooperative events in association with homeobox gene up-regulation to induce T
      cell leukemogenesis.

PMID- 16804920
TI  - Partial field-of-view spiral phase-contrast imaging using complex difference
      processing.
AB  - Rapid flow imaging was achieved with a partial field of view (pFOV) spiral motion
      encoded technique. The FOV and the acquisition time were reduced by a factor of 2
      by undersampling k-space. The pFOV spiral k-space trajectory aliased signals from
      outside a circular ring whose radius was inversely proportional to the distance
      between adjacent spirals in k-space. In this study the FOV was adjusted so that
      all of the moving spins were located inside the inner half circle of the full
      FOV. Complex subtraction of two differentially flow-encoded images was used to
      remove the spurious phase sources and provide an accurate measurement of flow.
      The complex subtraction process also serves to eliminate aliasing artifacts that
      are generated by static tissue from outside the reduced FOV. Experiments in a
      flow phantom and volunteers showed that the flow estimates obtained by pFOV
      spiral motion encoding are in good agreement with the estimates reconstructed
      using complex difference processing.

PMID- 16804921
TI  - Ultrastructure of the spermatid of Caprimulgus europaeus Linnaeus 1758, the
      European nightjar (Aves; Caprimulgidae), with phylogenetic implications.
AB  - The sperm of Caprimulgus europaeus is typical of other nonpasserines in many
      respects. Features shared with Paleognathae and Galloanserae are the conical
      acrosome, shorter than the nucleus; the presence of a perforatorium and
      endonuclear canal; the presence of a proximal as well as distal centriole; the
      elongate midpiece with mitochondria grouped around a central axis (here maximally
      six mitochondria in approximately 10 tiers); and the presence of a fibrous or
      amorphous sheath around the principal piece of the axoneme. A major (apomorphic)
      difference from paleognaths and galloanserans is the short distal centriole, the
      midpiece being penetrated for most of its length by the axoneme and for only a
      very short proximal portion by the centriole. Nonpasserines differ from
      paleognaths in that the latter have a transversely ribbed fibrous sheath, whereas
      in nonpasserines it is amorphous, as in Caprimulgus, or absent. The absence of an
      annulus is an apomorphic feature of Caprimulgus, apodiform, psittaciform,
      gruiform, and passerine sperm, homoplastic in at least some of these. In contrast
      to passerines, in Caprimulgus the cytoplasmic microtubules in the spermatid are
      restricted to a transient longitudinal manchette. The structure of the spermatid
      and spermatozoon is consistent with placement of the Caprimulgidae near the
      Psittacidae, but is less supportive of close proximity to the Apodidae, from DNA
      DNA hybridization and some other analyses.

PMID- 16804922
TI  - Effect of the potassium channel opener WAY-133537 on the overactive bladder of
      spinalized rats.
AB  - AIMS: To test the efficacy of WAY-133537 for the treatment of overactive bladder
      (OAB) in a chronic paraplegic rat model. MATERIALS AND METHODS: Forty-eight
      female Sprague-Dawley rats were used in this study. Six animals served as normal
      controls (without spinal cord transaction (ST)), while 42 rats underwent ST at
      the 10th thoracic vertebra. Two weeks after ST, cystometrogram (CMG) was
      performed in six randomly chosen animals to ensure the development of neurogenic
      detrusor overactivity. The remaining 36 rats were divided into three equal
      groups, 12 received the vehicle as "paraplegic controls," 12 received WAY-133537
      0.3 mg/kg, and 12 received WAY-133537 3 mg/kg. Each "paraplegic control" and
      treatment group was further divided into two sub-groups (n = 6), with CMG at 3
      and 4 weeks after ST, respectively. RESULTS: Two weeks after ST, all "vehicle
      control" rats developed detrusor overactivity with a mean frequency of 0.96 and
      1.48 contractions/min and amplitude of 22.96 and 31.22 cm H(2)O with 1- and 2
      week treatment, respectively. Neurogenic detrusor overactivity disappeared from
      50% of rats that received WAY-133537 0.3 mg/kg for 1 week, and frequency
      decreased to 0.41 contractions/min. After 2 weeks of treatment, detrusor
      overactivity vanished from 67% of the animals with even further reduction in the
      frequency of detrusor overactivity (0.22 contractions/min, P < 0.01). In rats
      that received 3 mg/kg of the drug for 1 week, detrusor overactivity disappeared
      from only one animal with a non-significant decline in frequency. Fifty percent
      of rats given WAY-133537 at the dose of 3 mg/kg/day for 2 weeks manifested no
      detrusor overactivity. CONCLUSIONS: WAY-133537 shows efficacy in increasing
      bladder capacity and reducing the frequency of spontaneous bladder contractions
      after ST in rats without decreasing voiding pressure.

PMID- 16804923
TI  - Long-term effects of the treatment of polycythemia vera with recombinant
      interferon-alpha.
AB  - Patients with polycythemia vera (PV) are most often treated with phlebotomy-only
      (PHL-O) or phlebotomy plus hydroxyurea (PHL + HU). Such treatment is often
      unsatisfactory because of persistent susceptibility to thrombosis owing to
      inadequate control of abnormal erythropoiesis and thrombopoiesis. Recombinant
      interferon-alpha (rIFN alpha) inhibits erythroid progenitors and affects
      megakaryocyte function and thus may be a more effective treatment, but reports of
      its use have been of relatively short duration. The long-term use (median, 13
      years) of rIFN alpha in 55 patients previously treated with PHL alone or with PHL
      + HU was studied. Data pertaining to the natural history of the disease were also
      examined. Patients achieved partial response of their disease by 6 months, and
      complete response by 1-2 years (phlebotomy-free, HCT < or =45%, platelets < or
      =600,000/microL); spleen size was reduced in 27 of 30 patients with prior
      splenomegaly. The initial dose of rIFN alpha was 1 mega unit 3 times a week (1
      MU/tiw) for the majority of patients, with periodic dose increases as required
      and as tolerated. The maintenance dose, usually 3 MU/tiw, could be decreased
      after the second year of treatment in half the patients. Toxicity was acceptable.
      Disease-free survival was marked by no thrombohemorrhagic complications
      reflecting both the effect of rIFN alpha and total patient care. Evidence is
      presented indicating that rIFN alpha effectively reduces PHL requirements,
      thrombocythemia, splenomegaly, and thrombohemorrhagic events. It is an effective
      drug for treating PV with acceptable toxicity.

PMID- 16804924
TI  - Additional axillary metastases and stage migration in breast cancer patients with
      micrometastases or submicrometastases in sentinel lymph nodes.
AB  - BACKGROUND: In patients with breast cancer, micrometastases and
      submicrometastases are increasingly found in sentinel nodes when step sectioning
      and/or immunohistochemical staining are applied. The aims of the current study
      were to investigate the incidence of micro- and submicrometastases in the
      sentinel node, to estimate the risk of additional metastases in the remaining
      axillary lymph nodes, and to consider implications for staging and treatment.
      METHODS: A total of 2150 breast cancer patients who had undergone axillary
      sentinel node biopsy between 1999 and 2004 were retrospectively evaluated.
      RESULTS: In all, 649 patients (30%) had a tumor-positive axillary sentinel node.
      Of these 649 patients, 148 had (23%) micrometastases and 105 (16%)
      submicrometastases. Of the 148 patients with micrometastases, 106 underwent
      axillary lymph node dissection (ALND) and additional metastases were found in 20
      patients (19%). Sixteen (15%) had macrometastases and were upstaged. The other 4
      patients had additional micrometastases. Seven of the 106 patients (7%) received
      additional systemic treatment based on the findings in the axillary lymph nodes.
      Fifty-four of the 105 patients with submicrometastases underwent ALND. Two (4%)
      of them had additional macrometastases and were upstaged and 2 had additional
      micrometastases. None received additional treatment based on the ALND findings.
      CONCLUSIONS: Of the involved sentinel nodes, 23% contained micrometastases and
      16% submicrometastases. Additional macrometastases were found in 15% and 4%,
      respectively, and treatment was altered in 7%. Based on these findings, offering
      additional treatment of the axilla is suggested in patients with micrometastases,
      but refraining from ALND in patients with submicrometastases in their sentinel
      node.

PMID- 16804925
TI  - Impact of chemotherapy regimens prior to endocrine therapy: Results from the ATAC
      (Anastrozole and Tamoxifen, Alone or in Combination) trial.
AB  - BACKGROUND: The 33-month median follow-up of the ATAC (anastrozole and tamoxifen,
      alone or in combination) trial showed a potential interaction between anastrozole
      and previous chemotherapy; however, this was much smaller at 47 months' median
      follow-up. When the effects of different chemotherapy regimens were evaluated at
      that time, the apparent interaction was limited to patients who had received
      cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). METHODS: In this
      retrospective analysis of 68-month data, we investigated the impact of prior
      chemotherapy, including different chemotherapy regimens, on time to recurrence.
      The chemotherapy regimens were 1) CMF only; 2) anthracycline-containing regimens
      (anthracycline or anthracycline and CMF); and 3) other chemotherapy regimens,
      including taxane-containing combinations. RESULTS: No evidence was found for an
      interaction between prior chemotherapy and anastrozole (hazard ratio [HR] 0.89
      vs. 0.74 for those with or without prior chemotherapy, respectively; P = .21 for
      interaction). For those with prior chemotherapy, the HR of anastrozole when
      compared with that of tamoxifen shifted from 0.98 (95% confidence intervals [CI],
      0.76-1.28) at 47 months' median follow-up to 0.89 (95% CI, 0.71-1.12) at 68
      months' median follow-up and was closer to the overall treatment effect (HR,
      0.79; 95% CI, 0.70-0.90). No differences according to type of chemotherapy were
      seen, and a benefit for anastrozole was also now apparent for patients receiving
      prior CMF (HR, 0.89; 95% CI, 0.63-1.24). CONCLUSIONS: On the basis of the 5-year
      Completed Treatment Analysis, the ATAC trial does not indicate that the relative
      treatment benefits of anastrozole differ significantly between patients who
      received prior chemotherapy and those who did not.

PMID- 16804927
TI  - Randomized phase II study of atrasentan alone or in combination with zoledronic
      acid in men with metastatic prostate cancer.
AB  - BACKGROUND: Metastatic prostate cancer is characterized by the presence of
      osteoblastic bone metastases. Bone metastases account for most of the morbidity
      from this disease. Inhibition of osteoclast activity with the potent
      bisphosphonate zoledronic acid reduces skeletal complications and decreases serum
      levels of biochemical bone turnover markers compared with placebo. Atrasentan is
      an investigational agent that inhibits endothelin-1 receptor, resulting in
      decreased osteoblast activity. METHODS: The effects of atrasentan alone versus
      combination therapy with atrasentan and zoledronic acid were investigated on bone
      turnover markers in men with bone metastases from prostate cancer. Forty-four men
      were randomized to receive either atrasentan alone or combination therapy, and 33
      completed at least 12 weeks of treatment and were included in the primary
      analysis. RESULTS: Treatment with the combination resulted in significantly lower
      serum levels of N-telopeptide, a marker of bone resorption, compared with
      treatment with atrasentan alone. There was no difference between groups in serum
      levels of bone-specific alkaline phosphatase, a marker of bone formation, at 12
      weeks. Commonly observed adverse effects were edema, rhinitis, fatigue, and
      shortness of breath, most of which were NCI CTC (version 3.0) Grade 1. No Grade 4
      or 5 treatment-related toxicities were observed. There was minimal clinical
      efficacy, with no objective responses and only 1 prostate-specific antigen (PSA)
      response. CONCLUSIONS: There is no evidence for additive or synergistic effects
      of combination therapy with atrasentan and zoledronic acid on bone turnover
      markers in men with metastatic prostate cancer.

PMID- 16804926
TI  - The prognostic value of hemoglobin change after initiating androgen-deprivation
      therapy for newly diagnosed metastatic prostate cancer: A multivariate analysis
      of Southwest Oncology Group Study 8894.
AB  - BACKGROUND: The objective of this study was to characterize changes in hemoglobin
      (HGB) levels after the initiation of androgen-deprivation therapy (ADT) in
      patients with previously untreated, metastatic prostate cancer who were enrolled
      in a large clinical trial. METHODS: The multivariate associations between 3-month
      change in HGB and baseline characteristics were evaluated with a linear
      regression model. The associations between 3-month change in HGB level and time
      to-event outcomes, including overall survival and progression-free survival, were
      evaluated by using proportional hazards regression models. RESULTS: Quartiles of
      baseline HGB levels were < or =12.0 g/dL, from 12.1 to 13.7 g/dL, from 13.8 to
      14.7 g/dL, and >14.7 g/dL. Overall, 3 months after initiating ADT, the mean HGB
      level declined 0.54 g/dL (standard deviation [SD], 1.68 g/dL); however, the mean
      HGB level increased by 0.99 g/dL (SD, 1.83 g/dL) in patients who had baseline HGB
      levels <12 g/dL and decreased 1.04 g/dL (SD, 1.28 g/dL) in patients who had
      baseline HGB levels > or =12 g/dL. After adjusting for potential confounders,
      including baseline HGB level, a decline in HGB after 3 months of ADT was
      associated independently with shorter survival (hazards ratio [HR], 1.10 per 1
      g/dL decline; P = .0035) and shorter progression-free survival (HR, 1.08 per 1
      g/dL decline; P = .013). An unexpected finding was that the effect of baseline
      HGB on overall and progression-free survival varied significantly by race.
      CONCLUSIONS: In a sample of men with newly diagnosed, metastatic prostate cancer,
      a decline in HGB level after 3 months of ADT was associated with shorter survival
      and progression-free survival after adjusting for disease status and other
      baseline covariates. Although race alone was not a strong predictor of death or
      disease progression, the effect of the baseline HGB level on overall and
      progression-free survival varied significantly by race.

PMID- 16804928
TI  - Role of chemotherapy for patients with recurrent platinum-resistant advanced
      epithelial ovarian cancer: A cost-effectiveness analysis.
AB  - BACKGROUND: Current chemotherapy in platinum-resistant ovarian cancer patients
      has demonstrated minimal to no improvements in survival. Despite the lack of
      benefit, significant resources are utilized with such therapies. Therefore, the
      objective in the current study was to assess the cost-effectiveness of salvage
      chemotherapy for patients with platinum-resistant epithelial ovarian cancer
      (EOC). METHODS: A decision analysis model evaluated a hypothetical cohort of 4000
      platinum-resistant patients with recurrent EOC. Several chemotherapy strategies
      were analyzed: 1) best supportive care (BSC); 2) second-line chemotherapy
      monotherapy; 3) second-line chemotherapy-combination therapy; 4) third-line
      chemotherapy after disease progression on second-line monotherapy; and 5) third
      line chemotherapy after disease progression on second-line combination therapy.
      Sensitivity analyses were performed on all pertinent uncertainties. RESULTS:
      Using costs alone, BSC was the only definitive cost-effective treatment for
      platinum-resistant recurrent ovarian cancer patients, and second-line monotherapy
      was a reasonable cost-effective strategy with an incremental cost-effectiveness
      ratio (ICER) of 64,104 dollars. The cost-effectiveness ranged from 4,065 dollars
      per month of overall survival (OS) for BSC to 12,927 dollars for third-line
      previous combination therapy. Compared with BSC, second-line monotherapy gained
      an additional 3 months of OS, with a cost-effectiveness of 4,703 dollars per
      month of OS. Second-line combination therapy and third-line therapies exhibited
      unfavorable ICER. CONCLUSIONS: The current decision analysis was intended to be
      thought-provoking and bring awareness to the high costs of subsequent
      chemotherapy with limited effectiveness in patients with recurrent platinum
      resistant EOC. Although actual patients may receive multiple lines of
      chemotherapy, from the perspective of costs alone this model using a hypothetical
      cohort demonstrated that best supportive care was the only cost-effective
      strategy, with second-line monotherapy appearing to be a reasonable cost
      effective strategy given current chemotherapeutic options.

PMID- 16804929
TI  - Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus
      radiotherapy with amifostine 5 times weekly: A prospective randomized study in
      squamous cell head and neck cancer.
AB  - BACKGROUND: The main objective of this study was to investigate whether nondaily
      intravenous administration of amifostine was as effective as daily intravenous
      administration with regard to the reduction of the incidence of Grade 2 or
      greater xerostomia in patients with head and neck cancer. METHODS: Ninety-one
      patients who received bilateral irradiation for head and neck cancer were
      included. Thirty patients received no amifostine (AMI-0), 31 patients received
      amifostine at a dose of 200 mg/m2 3 times weekly (AMI-3), and 30 patients
      received amifostine at a dose of 200 mg/m2 daily (5 times weekly) (AMI-5). Acute
      and late xerostomia and quality of life (QOL) were assessed at baseline, 6 weeks
      later, and at 6-month intervals from 6 months to 24 months postradiotherapy.
      RESULTS: Grade 2 or greater late xerostomia differed significantly at 6 months
      (AMI-0 74% vs. AMI-3 67% vs. AMI-5 52%; P = .03), but not thereafter. During
      follow-up, patient-rated xerostomia deteriorated more in AMI-0 patients (mean
      difference score:, 52 for AMI-0 compared with 25 for AMI-3, and 29 for AMI-5; P =
      .01). Nausea and emesis were reported most frequently as side effect, but Grade 2
      or greater toxicity was observed in only 4 patients. However, 28% of patients
      discontinued amifostine before the end of radiotherapy. CONCLUSIONS: Long-term,
      patient-rated xerostomia was less for the AMI-3 and AMI-5 groups through 2-year
      follow-up, but no difference was noted between the AMI-3 and AMI-5 groups. For
      late xerostomia according to the Radiation Therapy Oncology Group criteria, the
      same effect was observed at 6 months, but not thereafter.

PMID- 16804931
TI  - Proton beam therapy for hepatocellular carcinoma with limited treatment options.
AB  - BACKGROUND: The authors conducted a retrospective review to define the usefulness
      of proton beam therapy for patients who had hepatocellular carcinoma (HCC) with
      limited treatment options. METHODS: Twenty-one patients with HCC for whom other
      treatment modalities either were contraindicative or were unfeasible because of
      coexisting diseases and unfavorable conditions received proton beam therapy. Four
      patients had renal failure, 2 patients had severe heart disease, 9 patients had
      severe cirrhosis, 1 patient had aplastic anemia, 1 patient had a dissecting
      abdominal aortic aneurysm before treatment, and 4 patients had bleeding tendency
      or unresectable tumors. Moreover, 2 of the latter 4 patients were allergic to
      iodine, and 2 other patients were unable to be catheterized for transcatheter
      arterial chemoembolization. Hepatic tumors were solitary in 14 patients and
      multiple in 7 patients, and the tumors ranged in greatest dimension from 25 mm to
      100 mm (median, 40 mm). No patient had regional lymph node or distant metastasis.
      Total doses of 63 grays (Gy) to 84 Gy (median, 73 Gy) in 13 to 27 fractions
      (median, 18 fractions) were used for tumor treatments. RESULTS: All but 1 of the
      irradiated tumors were controlled at a median follow-up of 3.3 years. The
      objective response rate was 81%, and the primary site-control rate was 93% at 5
      years. Eleven patients had intrahepatic recurrences, and 2 patients had distant
      metastases in the lungs. Four of 11 patients with intrahepatic recurrences
      received a second course of proton beam therapy, and all recurrent tumors were
      controlled. The overall and cause-specific survival rates were 62% and 82% at 2
      years, respectively, and 33% and 67% at 5 years, respectively. Grade > or =3
      therapy-related toxicities were not observed. CONCLUSIONS: Proton beam therapy
      was safe and effective for a variety of patients with HCC. The current results
      suggested that this method was tolerable and effective, even for patients with
      HCC who had limited treatment options.

PMID- 16804930
TI  - Overexpression of podoplanin in oral cancer and its association with poor
      clinical outcome.
AB  - BACKGROUND: Podoplanin is a mucin-like glycoprotein that is important in
      lymphangiogenesis but not blood vessel formation. Recent studies suggested a
      potential role of podoplanin in certain tumor cells. The purpose of the current
      study was to determine the role of podoplanin in head and neck squamous cell
      carcinoma (HNSCC). METHODS: Podoplanin expression was analyzed in 35 patients
      with HNSCC including 16 oral tumors and 19 hypopharyngeal tumors by
      immunohistochemical analysis and the association between the podoplanin
      expression status and patients' clinical and pathologic characteristics was
      evaluated. An independent set of 60 patients with oral tongue cancer was then
      analyzed for associations between the podoplanin expression status and patients'
      clinical and pathologic characteristics, including survivals. RESULTS: Podoplanin
      was not expressed in normal oral epithelial cells but was detected in some
      hyperplastic and dysplastic lesions. High podoplanin expression was found in 20
      (57%) of the 35 tumors and was more frequent in tumors with lymph node
      metastasis, particularly for tumors in the oral cavity. In the second set of 60
      oral tongue cancers, 36 (60%) expressed high levels of podoplanin. Patients whose
      tumors expressed high levels of podoplanin had a statistically significantly
      higher rate of lymph node metastasis (P < .0001). Patients with lymph node
      metastasis and high-level podoplanin showed the shortest disease-specific
      survival (P = .0004) than other patients. CONCLUSIONS: Podoplanin is involved in
      oral tumorigenesis and may serve as a predictor for lymph node metastasis and
      poor clinical outcome.

PMID- 16804932
TI  - Epithelioid sarcoma: Still an only surgically curable disease.
AB  - BACKGROUND: Epithelioid sarcoma is a rare soft tissue sarcoma with a known high
      propensity for locoregional recurrence and distant metastases. The clinical
      behavior and prognostic factors that influence the survival of patients with
      epithelioid sarcoma were studied. METHODS: Twenty-three patients, including 16
      men (70%) and 7 women (30%), who were treated for epithelioid sarcoma between
      1979-2003 at the University Medical Center Groningen and Radboud University
      Nijmegen Medical Center, were reviewed retrospectively. The median age at
      diagnosis was 22 years (range, 1-54 years). At the time of diagnosis, 11 patients
      (48%) had metastases. Six patients with distant metastasis and 1 patient with an
      unresectable tumor received palliative treatment (30%). The remaining 16 patients
      underwent surgical treatment of local disease (11 patients) or locoregional
      disease (5 patients). Five patients in that group received isolated limb
      perfusion with tumor necrosis factor and melphalan. RESULTS: The 5-year and 10
      year disease-free survival rates for all patients were 34% and 17%, respectively;
      for the 16 patients who received curative treatment, both rates were 56%. In the
      latter group, 8 patients developed local recurrence (50%) after a median follow
      up of 4 months (range, 1-14 months). Nine patients were disease free after a
      median follow-up of 50 months (range, 6-290 months). Tumor size >5 cm (P < .0026)
      at diagnosis and local recurrence (P < .0008) were significant predictors of
      survival. CONCLUSIONS: The prognosis for patients with epithelioid sarcoma is
      poor, because a substantial number of patients present with extensive disease,
      lymph node metastases, and/or distant metastases. Treatment consists of radical
      surgical excision of the tumor and, if indicated, therapeutic lymph node
      dissection. In patients who have large tumors, isolated limb perfusion may be
      useful.

PMID- 16804933
TI  - Improved outcome in the treatment of pediatric multifocal Langerhans cell
      histiocytosis: Results from the Japan Langerhans Cell Histiocytosis Study Group
      96 protocol study.
AB  - BACKGROUND: The treatment outcome of multifocal childhood Langerhans cell
      histiocytosis (LCH) has not been satisfactory and has resulted in poor
      therapeutic responses with high mortality and a high incidence of reactivation
      with late sequelae. To overcome these issues, the Japan LCH Study Group-96 (JLSG
      96) protocol was conducted prospectively from 1996 to 2001 in Japan. METHODS:
      Newly diagnosed children with multifocal LCH were classified into 2 groups: a
      single-system multisite (SS-m) group and a multisystem (MS) group. All patients
      initially were treated on Protocol A, which consisted of 6 weeks of induction
      therapy with combined cytosine arabinoside, vincristine (VCR), and prednisolone
      (PSL) followed by 6 months of maintenance therapy. Patients who had a poor
      response to the induction of Protocol A were switched to a salvage regimen
      (Protocol B), which consisted of an intensive combination of doxorubicin,
      cyclophosphamide, VCR, and PSL. RESULTS: In total, 91 patients were treated,
      including 32 patients in the SS-m group and 59 patients in the MS group. At the
      median 5-year follow-up, 96.9% of patients in the SS-m group and 78.0% of
      patients in the MS group had good response status. Diabetes insipidus developed
      in 3.1% of patients in the SS-m group and in 8.9% of patients in the MS group.
      The overall survival rate at 5 years for the SS-m and MS groups was 100% and
      94.4% +/- 3.2%, respectively. CONCLUSIONS: The JLSG-96 protocol attained very low
      mortality for pediatric patients with multifocal LCH.

PMID- 16804934
TI  - Killer cell Ig-like receptors ligand-mismatched, alloreactive natural killer
      cells lyse primary solid tumors.
AB  - BACKGROUND: Donor alloreactive natural killer (NK) cells have a potent
      antileukemic effect in haploidentical stem cell transplantation. Whether
      alloreactive NK cells are able to specifically kill fresh tumor cells from
      primary solid tumors was analyzed. METHODS: NK cells were purified from healthy
      donors for the expression of inhibitory killer cell immunoglobulin (Ig)-like
      receptors (KIRs), ex vivo expanded, and used as effector cells. Their cytotoxic
      effect on tumor cells freshly obtained from surgical specimens was assessed by
      means of a single-cell cytotoxic assay (SCCA). RESULTS: Tumor cells from 1
      ovarian, 1 gastric, 3 colon, and 4 renal cell cancers were analyzed and found
      susceptible to alloreactive NK cell killing (>20% lysis at an effector cell to
      target cell [E:T] ratio of 10:1 for tumor cells not expressing at least 1 human
      lymphocyte antigen [HLA] class I KIR-ligand group). Remarkably, NK cells that
      recognized specific HLA-C group mismatches were able to kill HLA-C KIR ligand
      mismatched tumor cells, whereas no lysis of target cells occurred with KIR ligand
      matched tumor targets. CONCLUSIONS: Alloreactive NK-cell mediated antitumor
      effects might provide useful insights for designing new cell therapy approaches
      against solid tumors.

PMID- 16804935
TI  - Delayed profound thrombocytopenia associated with eptifibatide.

PMID- 16804936
TI  - Extensive exfoliative dermatitis induced by chlorambucil.

PMID- 16804937
TI  - Use of Novoseven for arsenic trioxide-induced bleeding in PML.

PMID- 16804938
TI  - Translocation (2;11)(p21;q23) in a patient with polycythemia vera: a novel clonal
      chromosome abnormality.

PMID- 16804939
TI  - Erythrocytosis associated with gestational hyperandrogenism.

PMID- 16804940
TI  - Clopidogrel-associated thrombotic thrombocytopenic purpura presenting with
      coronary artery thrombosis.

PMID- 16804941
TI  - Structural characterization of the Acetobacter xylinum endo-beta-1,4-glucanase
      CMCax required for cellulose biosynthesis.
AB  - Previous studies have demonstrated that endoglucanase is required for cellulose
      biosynthesis both in bacteria and plants. However, it has yet to be elucidated
      how the endoglucanases function in the mechanism of cellulose biosynthesis. Here
      we describe the crystal structure of the cellulose biosynthesis-related endo-beta
      1,47-glucanase (CMCax; EC 3.2.1.4) from the cellulose-producing Gramnegative
      bacterium, Acetobacter xylinum (= Gluconacetobacter xylinus), determined at 1.65
      A resolution. CMCax falls into the glycoside hydrolase family 8 (GH-8), and the
      structure showed that the overall fold of the CMCax is similar to those of other
      glycoside hydrolases belonging to GH-8. Structure comparison with Clostridium
      thermocellum CelA, the best characterized GH-8 endoglucanase, revealed that sugar
      recognition subsite +3 is completely missing in CMCax. The absence of the subsite
      +3 leads to significant broadness of the cleft at the cellooligosaccharide
      reducing-end side. CMCax is known to be a secreted enzyme and is present in the
      culture medium. However, electron microscopic analysis using immunostaining
      clearly demonstrated that a portion of CMCax is localized to the cell surface,
      suggesting a link with other known membrane-anchored endoglucanases that are
      required for cellulose biosynthesis.

PMID- 16804942
TI  - Crystal structures of human sulfotransferases SULT1B1 and SULT1C1 complexed with
      the cofactor product adenosine-3'- 5'-diphosphate (PAP).

PMID- 16804943
TI  - Reactive azo dye reduction by Shewanella strain J18 143.
AB  - A bacterial isolate designated strain J18 143, originally isolated from soil
      contaminated with textile wastewater, was shown to reduce intensely coloured
      solutions of the reactive azo dye, Remazol Black B to colourless solutions.
      Phylogenetic placement based on 16S rRNA gene sequence homology identified the
      bacterium as a Shewanella species. Based on results from analyses of the end
      products of dye decoloration of Remazol Black B and the simpler molecule, Acid
      Orange 7, using capillary electrophoresis, UV-visible spectrophotometry and
      liquid chromatography-mass spectrometry, we suggest that colour removal by this
      organism was a result of microbially mediated reduction of the chromophore in the
      dye molecules. Anaerobic dye reduction by Shewanella strain J18 143 was 30 times
      more efficient than the reduction carried out by aerated cultures. Whole cells
      used a range of electron donors for dye reduction, including acetate, formate,
      lactate, and nicotinamide adenine dinucleotide (NADH), with formate being the
      optimal electron donor. The impact of a range of process variables was assessed
      (including nitrate, pH, temperature, substrate concentration, presence of an
      extracellular mediator) and results suggest that whole cells of Shewanella J18
      143 offer several advantages over other biocatalysts with the potential to treat
      azo dyes.

PMID- 16804944
TI  - Overcoming the thermodynamic limitation in asymmetric hydrogen transfer reactions
      catalyzed by whole cells.
AB  - Whole lyophilized cells of an Escherichia coli overexpressing the alcohol
      dehydrogenase (ADH-'A') from Rhodococcus ruber DSM 44541 were used for the
      asymmetric reduction of ketones to secondary alcohols. The recycling of the
      required nicotinamide cofactor (NADH) was achieved in a coupled-substrate
      process. In the course of the reaction the ketone is reduced to the alcohol and
      the hydrogen donor 2-propanol is oxidized to acetone by one enzyme. This leads to
      a thermodynamic equilibrium between all four components determining the maximum
      achievable conversion. To overcome this limitation an in situ product removal
      technique (ISPR) for the application with whole cells was developed. In this
      method the most volatile compound is separated from the reaction vessel by an air
      flow resulting in a shift of the equilibrium towards the desired secondary
      alcohol. The so-called stripping process represents a simple and efficient method
      to overcome the thermodynamic limitation in biocatalytic reactions. Employing
      this method, the conversion of selected biotransformations was increased up to
      completeness.

PMID- 16804945
TI  - Crystallization of IgG1 by mapping its liquid-liquid phase separation curves.
AB  - Monoclonal antibody therapeutics is an important and fast expanding market. While
      production of these molecules has been a major area of research, much less is
      known regarding the stabilization of these proteins for delivery as drugs.
      Crystallization of antibodies is one such promising route for protein
      stabilization at high titers, and here we took a systematic approach to initiate
      crystallization through nucleation in a simple PEG (polyethylene glycol), protein
      in water solution. A ternary mixture of globular proteins, PEG, and water will
      undergo a liquid-liquid phase separation (LLPS) as shown in a phase diagram or a
      Binodal curve. Of particular interest within the phase diagram is the position of
      the critical point, which is where nucleation occurs most rapidly. Detailed LLPS
      maps were created by increasing concentrations of PEG (from 5% to 11%) and IgG
      (from 1 to 20 mg/mL). By increasing the molecular weight (MW) of PEG (and hence
      its radius of gyration) from 1,000 to 6,000 g/mol, the temperatures of the
      critical point of nucleation were shown to increase. Once these curves were
      determined, nucleation experiments were conducted close to a chosen critical
      point (10.5 mg/mL IgG in 11% PEG 1000) and after 3 weeks, crystals of IgG of
      approximately 100 microm in size were successfully formed. This is the first
      example of crystallization of an antibody through systematic mapping of LLPS
      curves, which is a fundamental step towards the scale-up of antibody
      crystallization.

PMID- 16804946
TI  - Characterization of sol-gel entrapped chlorophyllase.
AB  - Immobilization of membrane proteins remains a challenge compared to soluble
      proteins. The membrane protein-chlorophyllase was successful entrapped in
      tetramethoxysilane (TMOS)-based sol-gel in the presence of lipid. Activity was
      examined against mixing rate, incubation temperature, time, substrate, acetone,
      and canola oil concentration. The external mass transfer of chlorophyll is not
      the rate-limiting step at higher mixing rates. Stability against temperature and
      acetone as denaturant was enhanced. In spite of the fact that an initial reaction
      lag phase was observed, 20% more chlorophyll was hydrolyzed, compared to reaction
      with free enzyme by the end of a 12 h assay. The initial lower activity
      demonstrated by entrapped chlorophyllase is likely due to the diffusion
      resistance of chlorophyll into and within the entrapment matrix. This hypothesis
      was substantiated by a low diffusion coefficient on the order of 10(-14) m(2)/s
      obtained for chlorophyll in nanoporous sol-gel particles. Pore size distribution
      of nanoporous wet TMOS-based sol-gel with or without protein was determined by
      thermoporometry. The change in pore morphology upon doping with chlorophyllase
      suggests that protein acts as a template during the sol-gel process.

PMID- 16804947
TI  - A model system for increasing the intensity of whole-cell biocatalysis:
      investigation of the rate of oxidation of D-sorbitol to L-sorbose by thin bi
      layer latex coatings of non-growing Gluconobacter oxydans.
AB  - We developed a novel <50-microm thick nano-porous bi-layer latex coating for
      preserving Gluconobacter oxydans, a strict aerobe, as a whole cell biocatalyst.
      G. oxydans was entrapped in an acrylate/vinyl acetate co-polymer matrix (T (g)
      approximately 10 degrees C) and cast into 12.7-mm diameter patch coatings
      (cellcoat) containing approximately 10(9) CFU covered by a nano-porous topcoat.
      The oxidation of D-sorbitol to L-sorbose was used to investigate the coating
      catalytic properties. Intrinsic kinetics was studied in microbioreactors using a
      pH 6.0 D-sorbitol, phosphate, pyruvate (SPP) non-growth medium at 30 degrees C,
      and the Michaelis-Menten constants determined. By using a diffusion cell,
      cellcoat and topcoat diffusivities, optimized by arresting polymer particle
      coalescence by glycerol and/or sucrose addition, were determined. Cryo-FESEM
      images revealed a two-layer structure with G. oxydans surrounded by <40-nm pores.
      Viable cell density, cell leakage, and oxidation kinetics in SPP medium for >150
      h were investigated. Even though the coatings were optimized for permeability,
      approximately 50% of G. oxydans viability was lost during cellcoat drying and
      further reduction was observed as the topcoat was added. High reaction rates per
      unit volume of coating (80-100 g/L x h) were observed which agreed with
      predictions of a diffusion-reaction model using parameters estimated by
      independent experiments. Cellcoat effectiveness factors of 0.22-0.49 were
      observed which are 20-fold greater than any previously reported for this G.
      oxydans oxidation. These nano-structured coatings and the possibility of
      improving their ability to preserve G. oxydans viability may be useful for
      engineering highly reactive adhesive coatings for multi-phase micro-channel and
      membrane bioreactors to dramatically increase the intensity of whole-cell
      oxidations.

PMID- 16804948
TI  - Ultra scale-down studies of the effect of flow and impact conditions during E.
      coli cell processing.
AB  - The ability to recover cells from a fermentation broth in an intact form can be
      an important criterion for determining the overall performance of a recovery and
      purification sequence. Disruption of the cells can lead to undesired
      contamination of an extracellular product with intracellular components and vice
      versa loss of intracellular products may occur. In particular, the value of
      directed location of a product in the periplasmic space of say Escherichia coli
      (E. coli) would be diminished by such premature non-selective cell disruption.
      Several options exist for cell recovery/removal; namely centrifugation, in batch
      or continuous configuration, filtration or membrane operations, and in selected
      cases expanded beds. The choice of operation is dependant on many variables
      including the impact on the overall process sequence. In all cases, the cells are
      exposed to shear stresses of varying levels and times and additionally such
      environments exist in ancillary operations such as pumping, pipe flow, and
      control valves. In this study, a small-scale device has been designed to expose
      cells to controlled levels of shear, time and impact in a way that seeks to mimic
      those effects that may occur during full-scale processes. The extent of cell
      breakage was found to be proportional to shear stress. An additional level of
      breakage occurred due to the jet impacting on the collecting surface. Here it was
      possible to correlate the additional breakage with the impact velocity, which is
      a function of the distance that the jet travels before meeting the collection
      surface and the initial jet velocity.

PMID- 16804949
TI  - Enhanced matrix synthesis in de novo, scaffold free cartilage-like tissue
      subjected to compression and shear.
AB  - Production of a de novo cartilage-like tissue construct is a goal for the repair
      of traumatic chondral defects. We aimed to enhance the matrix synthesis within a
      scaffold free, de novo cartilage-like tissue construct by way of mechanical load.
      A novel loading machine that enables the application of shear, as well as
      compression, was used to subject tissue engineered cartilage-like tissue to
      mechanical stress. The machine, which applies the load through a roller
      mechanism, can load up to 20 constructs with four different loading patterns
      simultaneously. The expression of mRNA encoding matrix products, and subsequent
      changes in matrix protein content, were analyzed after various loading regimes.
      The force applied to the immature tissue had a direct bearing on the short-term
      (first 4 h) response. A load of 0.5 N caused an increase in collagen II and
      aggrecan mRNA within an hour, with a peak at 2 h. This increased mRNA expression
      was translated into an increase of up to 60% in the glycosaminoglycan content of
      the optimally loaded constructs after 4 days of intermittent cyclical loading.
      Introducing pauses between load cycles reproducibly lead to an increase in
      GAG/DNA. In contrast, constant cyclical load, with no pause, lead to a decrease
      in the final glycosaminoglycan content compared with unloaded controls. Our data
      suggest that a protocol of mechanical stimulation, simulating in vivo conditions
      and involving shear and compression, may be a useful mechanism to enhance the
      properties of tissue engineered tissue prior to implantation.

PMID- 16804951
TI  - Reports of hyperkalemia after publication of RALES--a pharmacovigilance study.
AB  - PURPOSE: A population-based study and anecdotal reports have indicated that the
      publication of the Randomized Aldactone Evaluation Study (RALES) was associated
      with not merely a broader use of spironolactone in the treatment of heart
      failure, but also with a coinciding sharp increase in hyperkalemia-associated
      morbidity/mortality in patients also being treated with ACE-inhibitors. Data
      mining algorithms (DMAs) are being applied to spontaneous reporting system (SRS)
      databases in hopes of obtaining early warnings/additional insights into post
      licensure safety data. We applied two DMAs (i.e. multi-item gamma Poisson
      shrinker [MGPS] and proportional reporting ratios [PRRs]) to spontaneous
      reporting system (SRS) data to determine if these DMAs could have provided an
      earlier indication of a possible hyperkalemia safety issue. METHODS: MGPS and
      PRRs were retrospectively applied to US FDA-AERS, an SRS database. Year-by-year
      analysis and analysis of increasing cumulative time intervals were performed on
      cases in which both spironolactone and hyperkalemia and possibly related cardiac
      events had been reported. RESULTS: Neither of the DMAs initially provided a
      compelling signal of disproportionate reporting (SDR) for hyperkalemia after
      publication of RALES. However, using events consistent with clinical sequelae of
      hyperkalemia (e.g,. sudden death), SDRs were identified with PRRs. CONCLUSIONS:
      The quality and usefulness of data mining analysis is highly situation dependent
      and may vary with the knowledge and experience of the drug safety reviewer. Our
      analysis suggests that contemporary DMAs may have significant limitations in
      detecting increased frequency of labeled events in real-life prospective
      pharmacovigilance. There is a paucity of research in this area and we recommend
      further research for new approaches to detecting increased frequency of labeled
      events.

PMID- 16804952
TI  - Functional molecular assemblies.

PMID- 16804953
TI  - Hypervalent iodine goes catalytic.

PMID- 16804956
TI  - An unexpected ion-molecule adduct in negative-ion collision-induced decomposition
      ion-trap mass spectra of halogenated benzoic acids.
AB  - The ion observed at m/z 145 when product ion spectra of iodobenzoate anions are
      recorded using ion-trap mass spectrometers corresponds to the adduct ion
      [I(H(2)O)](-). The elements of water required for the formation of this adduct do
      not originate from the precursor ion but from traces of moisture present in the
      helium buffer gas. A collision-induced decomposition (CID) spectrum recorded from
      the [M-H](-) ion (m/z 251) derived from 3-iodo[2,4,5,6-(2)H(4)]benzoic acid also
      showed an ion at m/z 145. This observation confirmed that the m/z 145 is not a
      product ion resulting from a direct neutral loss from the carboxylate anion.
      (79)Bromobenzoate anions produce similar results showing an ion at m/z 97 for
      [(79)Br(H(2)O)](-). The ion-molecule reaction observed here is unique to ion-trap
      mass spectrometers since a corresponding ion was not observed under our
      experimental conditions in spectra recorded with in-space tandem mass
      spectrometers such as triple quadrupole or quadrupole time-of-flight instruments.

PMID- 16804957
TI  - Mass spectrometric identification and characterization of a new long-term
      metabolite of metandienone in human urine.
AB  - Anabolic-androgenic steroids are some of the most frequently detected drugs in
      amateur and professional sports. Doping control laboratories have developed
      numerous assays enabling the determination of administered drugs and/or their
      metabolic products that allow retrospectives with respect to pharmacokinetics and
      excretion profiles of steroids and their metabolites. A new metabolite generated
      from metandienone has been identified as 18-nor-17beta-hydroxymethyl,17alpha
      methyl-androst-1,4,13-trien-3-one in excretion study urine samples providing a
      valuable tool for the long-term detection of metandienone abuse by athletes in
      sports drug testing. The metabolite was characterized using gas
      chromatography/(tandem) mass spectrometry, liquid chromatography/tandem mass
      spectrometry and liquid chromatography/high-resolution/high-accuracy (tandem)
      mass spectrometry by characteristic fragmentation patterns representing the
      intact 3-keto-1,4-diene structure in combination with typical product ions
      substantiating the proposed C/D-ring structure of the steroid metabolite. In
      addition, structure confirmation was obtained by the analysis of excretion study
      urine specimens obtained after administration of 17-CD(3)-labeled metandienone
      providing the deuterated analogue to the newly identified metabolite. 18-Nor
      17beta-hydroxymethyl,17alpha-methyl-androst-1,4,13-trien-3-one was determined in
      metandienone administration study urine specimens up to 19 days after application
      of a single dose of 5 mg, hence providing an extended detection period compared
      with commonly employed strategies.

PMID- 16804959
TI  - A DFT study of the mechanism of Ni superoxide dismutase (NiSOD): role of the
      active site cysteine-6 residue in the oxidative half-reaction.
AB  - In the present DFT study, the catalytic mechanism of H2O2 formation in the
      oxidative half-reaction of NiSOD, E-Ni(II) + O2- + 2H+ --> E-Ni(III) + H2O2, has
      been investigated. The main objective of this study is to investigate the source
      of two protons required in this half-reaction. The proposed mechanism consists of
      two steps: superoxide coordination and H2O2 formation. The effect of protonation
      of Cys6 and the proton donating roles of side chains (S) and backbones (B) of
      His1, Asp3, Cys6, and Tyr9 residues in these two steps have been studied in
      detail. For protonated Cys6, superoxide binding generates a Ni(III)-O2H species
      in a process that is exothermic by 17.4 kcal/mol (in protein environment using
      the continuum model). From the Ni(III)-O2H species, H2O2 formation occurs through
      a proton donation by His1 via Tyr9, which relative to the resting position of the
      enzyme is exothermic by 4.9 kcal/mol. In this pathway, a proton donating role of
      His1 residue is proposed. However, for unprotonated Cys6, a Ni(II)-O2- species is
      generated in a process that is exothermic by 11.3 kcal/mol. From the Ni(II)-O2-
      species, the only feasible pathway for H2O2 formation is through donation of
      protons by the Tyr9(S)-Asp3(S) pair. The results discussed in this study
      elucidate the role of the active site residues in the catalytic cycle and provide
      intricate details of the complex functioning of this enzyme.

PMID- 16804960
TI  - Interaction or relationship between Helicobacter pylori and non-steroidal anti
      inflammatory drugs in upper gastrointestinal diseases.
AB  - According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs
      (NSAID) independently and significantly increase the risk of gastroduodenal ulcer
      and ulcer bleeding. Their coincidence is frequent, demonstration of a possible
      relationship and consequent attitude is of important implications. But
      unfortunately, no consensus has been approved in the past years and their
      interactions are still controversial. H pylori and NSAID are known to share a
      number of pathogenic mechanisms, but there is no evidence for the significant
      synergic action between these two risk factors. Their relationship is
      independent, additive, synergistic or antagonistic without considering the
      influence of other factors because studies on this subject are different in
      almost all aspects of their methodology, including the definition of a NSAID user
      as well as the types, doses, duration and their indications for NSAID use, as
      well as their end-points, definition of dyspepsia and regimes used for
      eradication of H pylori. These might contribute to the conflicting results and
      opinions. H pylori infection in humans does not act synergistically with NSAID on
      ulcer healing, and there is no need to eradicate it. This notion is supported by
      the finding that the eradication of H pylori does not affect NSAID-induced
      gastropathy treated with omeprazole and that H pylori infection induces a strong
      cyclooxygenase-2 (COX-2) expression resulting in excessive biosynthesis of
      gastroprotective prostaglandin which in turn counteracts NSAID-induced
      gastropathy and heals the existing ulcer. Other investigators claimed that H
      pylori infection acts synergistically with NSAID on ulcer development, and H
      pylori should be eradicated, particularly at the start of long-term NSAID
      therapy. Eradication of H pylori prior to NSAID treatment does not appear to
      accelerate ulcer healing or to prevent recurrent ulcers in NSAID users. However,
      some recommendations can be drawn from the results of clinical trails.

PMID- 16804961
TI  - Sphincter of Oddi dysfunction: managing the patient with chronic biliary pain.
AB  - Sphincter of Oddi dysfunction (SOD) is a syndrome of chronic biliary pain or
      recurrent pancreatitis due to functional obstruction of pancreaticobiliary flow
      at the level of the sphincter of Oddi. The Milwaukee classification stratifies
      patients according to their clinical picture based on elevated liver enzymes,
      dilated common bile duct and presence of abdominal pain. Type I patients have
      pain as well as abnormal liver enzymes and a dilated common bile duct. Type II
      SOD consists of pain and only one objective finding, and Type III consists of
      biliary pain only. This classification is useful to guide diagnosis and
      management of sphincter of Oddi dysfunction. The current gold standard for
      diagnosis is manometry to detect elevated sphincter pressure, which correlates
      with outcome to sphincterotomy. However, manometry is not widely available and is
      an invasive procedure with a risk of pancreatitis. Non-invasive testing methods,
      including fatty meal ultrasonography and scintigraphy, have shown limited
      correlation with manometric findings but may be useful in predicting outcome to
      sphincterotomy. Endoscopic injection of botulinum toxin appears to predict
      subsequent outcome to sphincterotomy, and could be useful in selection of
      patients for therapy, especially in the setting where manometry is unavailable.

PMID- 16804962
TI  - Tumor differentiation phenotype in gastric differentiated-type tumors and its
      relation to tumor invasion and genetic alterations.
AB  - AIM: To clarify the relations between tumor differentiation phenotype and tumor
      invasion or genetic alterations in gastric differentiated-type tumors. METHODS:
      We examined the tumor differentiation phenotype, the presence of mutations in APC
      and p53, and the microsatellite instability (MSI) status in 48 gastric adenomas
      and 171 differentiated-type carcinomas. The tumor differentiation phenotype was
      determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2
      and CD10. The tumors were then classified into gastric- (G-), gastric and
      intestinal mixed- (GI-), or intestinal- (I-) phenotypes, according to the
      immunopositivity of the above markers. The presence of mutations in APC and p53
      and the MSI status were also investigated in all the tumors. RESULTS: Gastric
      adenomas were significantly associated with CD10 expression, I-phenotype tumors
      and the presence of APC mutations, compared with carcinomas (66.7% vs 25.1%, P <
      0.0001; 56.3% vs 14.6%, P < 0.0001; 39.6% vs 14.0%, P < 0.0001, respectively) and
      inversely associated with expressions of HGM and MUC6 and the presence of p53
      mutations (10.4% vs 62.6%, P < 0.0001; 39.6% vs 64.3%, P = 0.003; 2.0% vs 26.3%,
      P = 0.001, respectively). The frequency of APC mutations was significantly higher
      in HGM-negative tumors, MUC6-negative tumors, CD10-positive tumors and I
      phenotype tumors than in HGM-positive tumors, MUC6-positive tumors, CD10-negative
      tumors and G-phenotype tumors (32.7% vs 7.1%, P < 0.0001; 27.8% vs 14.0%, P =
      0.0182; 37.3% vs 10.4%, P < 0.0001; and 38.5% vs 9.5%, P = 0.0017, respectively).
      The frequency of MSI was significantly higher in MUC6-positive tumors, CD10
      negative tumors and G-phenotype tumors than in MUC6-negative tumors, CD10
      positive tumors and I-phenotype tumors (24.8% vs 6.7%, P = 0.0009; 22.2% vs 8.0%,
      P = 0.0143; and 28.6% vs 9.6%, P = 0.0353, respectively). CONCLUSION: The tumor
      differentiation phenotype is closely related to tumor invasion and genetic
      alterations in gastric differentiated-type tumors.

PMID- 16804963
TI  - Effects of recombinant human growth hormone on growth of human gastric carcinoma
      xenograft model in nude mice.
AB  - AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a
      human gastric carcinoma cell in vivo. METHODS: Experimental mice were divided
      into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group.
      Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla
      of nude mice and carcinoma xenograft model was established successfully.
      Inhibitory rate of xenograft tumor growth was estimated by measuring tumor
      volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2
      proteins of xenograft tumor was detected using immunohistochemical S-P method.
      RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax
      and Bcl-2 were 49.3%, 58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively;
      46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in
      rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant
      difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH
      group (P < 0.05), whereas there were no significant differences (P > 0.05)
      between L-OHP group and rhGH+L-OHP group and between rhGH group and control
      group. CONCLUSION: rhGH does not accelerate the proli-feration of human gastric
      cancer cell in vivo.

PMID- 16804964
TI  - Single-tube-genotyping of gastric cancer related SNPs by directly using whole
      blood and paper-dried blood as starting material.
AB  - AIM: To demonstrate an inexpensive method for typing gastric cancer related
      single nucleotide polymorphisms (SNPs) using whole blood or paper-dried blood as
      starting materials. METHODS: PCR amplification is directly carried out from the
      whole blood or paper-dried blood sample without any DNA extraction step. Before
      PCR, a blood sample, four primers, and all of biological reagents necessary for
      PCR were added at a time; After PCR, the amplified products were directly
      separated by slab gel electrophoresis or microchip CE without any purification.
      SNP typing was performed by tetra-primer PCR with two inner primers specific to
      each allele and two outer primers defining the length of allele-specific
      amplicons. Genotypes were directly discriminated by the size of amplicons
      specific to each allele, thereby avoiding any post-PCR process. RESULTS: Using a
      special PCR buffer, inhibitory substances in blood (including the anticoagulant
      in blood) and filter paper were effectively suppressed; a "true" single-tube
      genotyping is thus realized. We successfully determined genotypes IL-1B-511 and
      IL-1B-31 polymorphisms at the gene IL-1B by using whole-blood and paper-dried
      blood samples as starting materials respectively. The method is so sensitive that
      0.5-1.0 microL of blood sample is enough to give a satisfactory typing results.
      The genotyping results were confirmed by RFLP-PCR using purified genome DNA,
      indicating that amplification specificity was not affected by inhibitory
      components (including coagulants) in blood or filter paper. CONCLUSION: Compared
      with SNP typing methods based on purified DNA, the proposed method is labor
      saving, simple, inexpensive, and less cross-contaminated. It is promising to use
      this method to type other SNPs.

PMID- 16804965
TI  - Increased hepatic expression of insulin-like growth factor-I receptor in chronic
      hepatitis C.
AB  - AIM: Although increased insulin-like growth factor-I receptor (IGF-IR) gene
      expression has been reported in hepatocellular carcinoma, studies assessing IGF
      IR in chronic hepatitis C (CHC) and cirrhosis are scarce. We therefore aimed to
      evaluate IGF-IR and IGF-I mRNA expression in liver from patient with CHC.
      METHODS: IGF-IR and IGF-I mRNA content were determined by semi-quantitative RT
      PCR and IGF-IR protein expression was determined by immunohisto-chemistry in
      hepatic tissue obtained from patients with CHC before (34 patients) and after (10
      patients) therapy with interferon-alpha and ribavirin. RESULTS: An increase of
      IGF-IR mRNA content was observed in hepatic tissue obtained from all CHC patients
      as well as from 6 cadaveric liver donors following orthopic transplantation (an
      attempt to evaluate normal livers) in comparison to normal liver, while no
      relevant modifications were detected in IGF-I mRNA content. The
      immunohistochemical results showed that the raise in IGF-IR mRNA content was
      related both to ductular reaction and to increased IGF-IR expression in
      hepatocytes. A decrease in IGF-IR mRNA content was observed in patients who
      achieved sustained virological response after therapy, suggesting an improvement
      in hepatic damage. CONCLUSION: The up-regulation of IGF-IR expression in
      hepatocytes of patients with CHC could constitute an attempt to stimulate
      hepatocyte regeneration. Considering that liver is the organ with the highest
      levels of IGF-I, our finding of increased IGF-IR expression after both acute and
      chronic hepatic damage highlights the need for additional studies to elucidate
      the role of IGF-I in liver regeneration.

PMID- 16804966
TI  - Defensive nature of Sargassum polycystum (Brown alga) against acetaminophen
      induced toxic hepatitis in rats: role of drug metabolizing microsomal enzyme
      system, tumor necrosis factor-alpha and fate of liver cell structural integrity.
AB  - AIM: To assess the defensive nature of Sargassum polycystum (S. polycystum)
      (Brown alga) against acetaminophen (AAP)-induced changes in drug metabolizing
      microsomal enzyme system, tumor necrosis factor (TNF-alpha) and fine structural
      features of the liver during toxic hepatitis in rats. METHODS: Male albino Wistar
      strain rats used for the study were randomly categorized into 4 groups. Group I
      consisted of normal control rats fed with standard diet. Group II rats were
      administered with acetaminophen (800 mg/kg body weight, intraperitoneally). Group
      III rats were pre-treated with S. polycystum extract alone. Group IV rats were
      orally pre-treated with S. polycystum extract (200 mg/kg body weight for 21 d)
      prior to acetaminophen induction (800 mg/kg body weight, intraperitoneally).
      Serum separated and liver was excised and microsomal fraction was isolated for
      assaying cytochrome P450, NADPH Cyt P450 reductase and b(5). Serum TNF-alpha was
      detected using ELISA. Fine structural features of liver were examined by
      transmission electron microscopy. RESULTS: Rats intoxicated with acetaminophen
      showed considerable impairment in the activities of drug metabolizing microsomal
      enzymes, such as cytochrome P450, NADPH Cyt P450 reductase and b(5) when compared
      with the control rats. The rats intoxicated with acetaminophen also significantly
      triggered serum TNF-alpha when compared with the control rats. These severe
      alterations in the drug metabolizing enzymes were appreciably prevented in the
      rats pretreated with S. polycystum. The rats pretreated with S. polycystum showed
      considerable inhibition in the elevation of TNF-alpha compared to the rats
      intoxicated with acetaminophen. The electron microscopic observation showed
      considerable loss of structural integrity of the endoplasmic reticulum, lipid
      infiltration and ballooning of mitochondria in the acetaminophen-intoxicated
      rats, whereas the rats treated with S. polycystum showed considerable protection
      against acetaminophen-induced alterations in structural integrity. CONCLUSION:
      These observations suggest that the animals treated with S. polycystum extract
      may have the ability to protect the drug metabolizing enzyme system and
      mitochondrial functional status from free radical attack, thereby showing its
      defense mechanism in protecting hepatic cells from acetaminophen toxic metabolite
      N-acetyl-para-benzoquinone-imine (NAPQI).

PMID- 16804967
TI  - Effect of liver regeneration after partial hepatectomy and ischemia-reperfusion
      on expression of growth factor receptors.
AB  - AIM: To investigate the effects of experimental partial hepatectomy and
      normothermic ischemia-reperfusion damage on the time course of the expression of
      four different growth factor receptors in liver regeneration. This is relevant
      due to the potential therapeutic use of growth factors in stimulating liver
      regeneration. METHODS: For partial hepatectomy (PH) 80% of the liver mass was
      resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by
      occlusion of the portal vein and the hepatic artery for 15 min. The epidermal
      growth factor receptor, hepatic growth factor receptor, fibroblast growth factor
      receptor and tumour necrosis factor receptor-1 were analysed by
      immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed
      at the time point of minimal receptor expression (24 h). RESULTS: In
      immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after
      partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak
      increase up to 72 h. During liver regeneration, after ischemia and reperfusion,
      the receptor expression was lower; the nadir at 24 h after reperfusion was the
      same. To evaluate whether this nadir was caused by a lack of mRNA transcription,
      or due to a posttranslational regulation, RT-PCR was performed at 24 h and
      compared to resting liver. In every probe there was specific mRNA for the
      receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in
      resting liver, HGFR expression after I/R was stronger than in the control.
      CONCLUSION: At least partially due to a post-transcriptional process, there is a
      nadir in the expression of the analysed receptors 24 h after liver injury.
      Therefore, a therapeutic use of growth factors to stimulate liver regeneration 24
      h after the damage might be not successful.

PMID- 16804968
TI  - Isolation, characterization and culture of Thy1-positive cells from fetal rat
      livers.
AB  - AIM: To investigate whether Thy1 recognizes oval cells in the fetal liver and to
      characterize the cultured Thy1- selected cells from E14 rat livers. METHODS: Thy1
      populations were analyzed by fluorescence activated cell sorter analysis. Thy1
      positive cells were isolated using magnetic beads. Hepatic markers were detected
      by Western blotting, immunocytochemistry and RT-PCR. RESULTS: The percentage of
      Thy1-positive cells decreased during early development of fetal rat liver (E13
      E16). E14 fetal livers contained 7.8% Thy1 positive cells, of which 61% were
      positive for alpha-fetoprotein (AFP) and 25% expressed albumin. The Thy1+
      population expressed oval cell markers c-Kit and CXCR4, liver enriched
      transcription factors HNF1alpha and HNF6, hepatocytic markers albumin, AFP and
      cytokeratin 18, and biliary marker cytokeratin 19. Thy1- selected cells formed
      only mesenchymal colonies when plated on collagen and in serum-containing media.
      Thy1 selected cells were able to form hepatic colonies positive for HNF1alpha,
      HNF6, albumin, AFP, cytokeratin 18, cytokeratin 19 and glycogen, when grown on
      STO feeder layers in serum free-media. CONCLUSION: Oval cells positive for Thy1
      are present in early liver embryonic stages.

PMID- 16804969
TI  - Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by
      inhibiting expression of cyclooxygenase-2.
AB  - AIM: To explore the possible mechanisms of curcumin in rat colitis induced by
      trinitrobenzene sulfonic (TNBS) acid. METHODS: Rats with TNBS acid-induced
      colitis were treated with curcumin (30 mg/kg or 60 mg/kg per day ip). Changes of
      body weight and histological scores as well as survival rate were evaluated.
      Leukocyte infiltration was detected by myeloperoxidase (MPO) activity assay. The
      expression of cyclooxygenase-2 (COX-2) was detected by RT-PCR and Western blot.
      Inflammation cytokines were determined by RT-PCR. Local concentration of
      prostaglandin E(2) (PGE(2)) in colon mucosa was determined by ELISA. RESULTS:
      Curcumin improved survival rate and histological image, decreased the macroscopic
      scores and MPO activity. Also curcumin reduced the expression of COX-2 and
      inflammation cytokines. In addition, treatment with curcumin increased the PGE(2)
      level. CONCLUSION: Curcumin has therapeutic effects on TNBS acid-induced colitis,
      the mechanisms seem to be related to COX-2 inhibition and PGE(2) improvement.

PMID- 16804970
TI  - Expression of macrophage inflammatory protein-1alpha in Kupffer cells following
      liver ischemia or reperfusion injury in rats.
AB  - AIM: To explore the expression of macrophage inflammatory protein-1alpha (MIP
      1alpha) in Kupffer cells (KCs) following liver ischemia/reperfusion injury IRI in
      rats. METHODS: Forty male SD rats were divided randomly into five groups. A model
      of partial warm ischemia/reperfusion injury in the rat liver was established. KCs
      were isolated and incubated one hour, six hours, 12 h, and 24 h after the
      reperfusion. Tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) in the supernatants were measured by ELISA. MIP-1alpha in KCs was detected
      by immunocytochemical and RT-PCR. RESULTS: No or few MIP-1alpha protein and mRNA
      were expressed in the KCs of the control group. Its expression in the IRI group
      had a significant increase after the reperfusion (P < 0.05), which was contrary
      to the control group. CONCLUSION: The active behavior of the MIP-1alpha gene in
      KCs following liver ischemia/reperfusion injury is assumed to be one of the major
      causes for the hepatic ischemia/reperfusion injury.

PMID- 16804971
TI  - High efficient mammalian expression and secretion of a functional humanized
      single-chain Fv/human interleukin-2 molecules.
AB  - AIM: To construct and produce a recombinant bispecific humanized single-chain Fv
      (sFv) /Interleukin-2 (IL-2) fusion protein by using mammalian cells. METHODS: The
      sFv/IL-2 protein was genetically engineered, and transfected to mammalian cells
      to determine whether the mammalian protein folding machinery can produce and
      secrete active sFv/IL-2 with high efficiency. RESULTS: The fusion protein was
      constructed and high efficiently expressed with yields up to 102 +/- 4.2 mg/L in
      culture supernatant of the stably transfected 293 cell line. This recombinant
      fusion protein consisted of humanized variable heavy (V(H)) and light (V(L))
      domains of monoclonal antibody (mAb) 520C9 directed against the human HER-2/neu
      (c-erbB2) proto-oncogene product p185, and human IL-2 connected by polypeptide
      linker. The fusion protein was shown to retain the immunostimulatory activities
      of IL-2 as measured by IL-2-dependent cell proliferation and cytotoxicity assays.
      In addition to its IL-2 activities, this fusion protein also possessed antigen
      binding specificity against p185, as determined by indirect ELISA using p185
      positive SKOV 3ip1 cells. CONCLUSION: The large-scale preparation of the
      recombinant humanized sFv antibody/IL-2 fusion protein is performed with 293
      cells. The recombinant humanized sFv antibody/IL-2 fusion protein may provide an
      effective means of targeting therapeutic doses of IL-2 to p185 positive tumors
      without increasing systemic toxicity or immunogenicity.

PMID- 16804972
TI  - Efficacy of balloon-occluded retrograde transvenous obliteration, percutaneous
      transhepatic obliteration and combined techniques for the management of gastric
      fundal varices.
AB  - AIM: To evaluate the effect of three interventional treatments involving
      transvenous obliteration for the treatment of gastric varices, and to compare the
      efficacy and adverse effects of these methods. METHODS: From 1995 to 2004, 93
      patients with gastric fundal varices underwent interventional radiologic
      embolotherapy at our hospital. Of the 93 patients, 75 were treated with the
      balloon-occluded retrograde transvenous obliteration (BRTO) procedure; 8 were
      with the percutaneous transhepatic obliteration (PTO) procedure; and 10 were with
      the combined BRTO and PTO therapy. A follow-up evaluation examined the rates of
      survival, recurrence and rebleeding of the gastric varices, worsening of
      esophageal varices and complications in each group. RESULTS: The BRTO, PTO, and
      combined therapy were technically successful in 81% (75/93), 44% (8/18), and 100%
      (10/10) patients, respectively. Recurrence of gastric varices was found in 3
      patients in the BRTO group and in 3 patients in the PTO group. Rebleeding was
      observed in 1 patient in the BRTO group and in 1 patient in the PTO group. The 1-
      and 3-year survival rates were 98% and 87% in the patients without hepatocellular
      carcinoma (HCC) in the BRTO group, 100% and 100% in the PTO group, and 90% and
      75% in the combined therapy group, respectively. CONCLUSION: Combined BRTO and
      PTO therapy may rescue cases with uncontrollable gastric fundal varices that
      remained even after treatment with BRTO and/or PTO, though there were limitations
      of our study, including retrospective nature and discrepancy in sample size
      between the BRTO, PTO and combined therapy groups.

PMID- 16804973
TI  - Family history of irritable bowel syndrome is the major determinant of persistent
      abdominal complaints in young adults with a history of pediatric recurrent
      abdominal pain.
AB  - AIM: To assess the late outcome of teen-agers with a previous history of
      recurrent abdominal pain (RAP) or irritable bowel syndrome (IBS). METHODS: A
      group of 67 children with RAP referred to the department from January 1986 to
      December 1995 was followed up between 5 and 13 years after the initial diagnosis
      by means of a structured telephone interview. We hypothesized that those patients
      with persistent adult IBS-like symptoms would be significantly more likely to
      report a family history of IBS in comparison with adults with no persistent
      abdominal complaint. RESULTS: Out of the 52 trackable subjects, 15 were found to
      present IBS-like symptoms at follow-up (29%) whereas the majority (37 subjects)
      did not. Subjects with IBS-like symptoms were almost three times more likely to
      present at least one sibling with similar symptoms compared to subjects not
      complaining (40.0% vs 16.0%), respectively (P < 0.05 at Student t test). Subjects
      with IBS-like symptoms also reported a higher prevalence of extra-intestinal
      symptoms, such as back pain, fibromyalgia, headache, fatigue and sleep
      disturbances. CONCLUSION: The study confirms previous observations indicating
      that pediatric RAP can predict later development of IBS. The latter appears to be
      greatly influenced by intrafamilial aggregation of symptoms, possibly through the
      learning of a specific illness behavior.

PMID- 16804974
TI  - Overexpression of c-met in the early stage of pancreatic carcinogenesis; altered
      expression is not sufficient for progression from chronic pancreatitis to
      pancreatic cancer.
AB  - AIM: To investigate c-met expression during early pancreatic carcinogenesis.
      METHODS: We used 46 bulk tissues and 36 micro-dissected samples, including normal
      pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative real-time
      reverse transcription-polymerase chain reaction. RESULTS: In bulk tissue
      analyses, pancreatic cancer tissues expressed significantly higher levels of c
      met than did chronic pancreatitis and normal pancreas tissues. c-met levels did
      not differ between chronic pancreatitis and normal pancreas tissues. In
      microdissection-based analyses, c-met was expressed at higher levels in
      microdissected pancreatic cancer cells and pancreatitis-affected epithelial cells
      than in normal ductal epithelial cells (both, P < 0.01). Interestingly,
      pancreatitis-affected epithelial cells expressed levels of c-met similar to those
      of pancreatic cancer cells. CONCLUSION: Overexpression of c-met occurs during the
      early stage of pancreatic carcinogenesis, and a single alteration of c-met
      expression is not sufficient for progression of chronic pancreatitis-affected
      epithelial cells to pancreatic cancer cells.

PMID- 16804975
TI  - Influence of a microscopic positive proximal margin in the treatment of gastric
      adenocarcinoma of the cardia.
AB  - AIM: To investigate the influence of a positive proximal margin in total
      gastrectomy patients with gastric adenocarcinoma of the cardia. METHODS: Medical
      records of 191 patients with total gastrectomies for adenocarcinoma of the cardia
      between 1995 and 2000 were reviewed. The clinicopathologic features associated
      with a positive margin were determined, and the predictors for survival were
      analyzed. RESULTS: The incidence of positive proximal margin was 8.4% (16/191).
      The positive margins were associated with advanced diseases. The tumor size and
      the depth of tumor invasion were independent risk factors for a positive margin.
      The mean survival in the positive margin group was 33.9 mo as compared with 62.4
      mo in the negative group (P < 0.001). However, the difference in survival lost
      significance in subgroup analysis according to stage. Multivariate analysis
      identified that a positive margin was not an independent prognostic factor for
      survival. CONCLUSION: A positive margin is more of an indication of advanced
      disease in patients with gastric adenocarcinoma of the cardia rather than an
      independent prognostic factor for survival.

PMID- 16804976
TI  - Laparoscopic cholecystectomy: a report from a single center.
AB  - AIM: To review and evaluate our experience in laparoscopic cholecystectomy.
      METHODS: A retrospective analysis was performed on data collected during a 13
      year period (1992-2005) from 1220 patients who underwent laparoscopic
      cholecystectomy. RESULTS: Mortality rate was 0%. The overall morbidity rate was
      5.08% (n = 62), with the most serious complications arising from injuries to the
      biliary tree and the cystic artery. In 23 (1.88%) cases, cholecystectomy could
      not be completed laparoscopically and the operation was converted to an open
      procedure. Though the patients were scheduled as day-surgery cases, the average
      duration of hospital stay was 2.29 d, as the complicated cases with prolonged
      hospital stay were included in the calculation. CONCLUSION: Laparoscopic
      cholecystectomy is a safe, minimally invasive technique with favorable results
      for the patient.

PMID- 16804977
TI  - Value of carcinoembryonic antigen and cytokeratins for the detection of recurrent
      disease following curative resection of colorectal cancer.
AB  - AIM: To evaluate the efficacy of postoperative serial assay of carcinoembryonic
      antigen (CEA) and cytokeratins for the detection of recurrent disease in patients
      with colorectal adenocarcinoma after radical surgery. METHODS: Between 1993 and
      2000, 120 patients with colorectal adenocarcinoma underwent radical surgery in
      the Department of Surgical Gastroenterology, Federal University of Sao Paulo
      Escola Paulista de Medicina, Sao Paulo, Brazil. Periodic postoperative evaluation
      was performed by assaying markers in peripheral serum, colonoscopy and imaging
      examination. Presence of CEA was detected using the Delfia method with 5 microg/L
      threshold, and cytokeratins using the LIA-mat TPA-M Prolifigen method with 72 U/L
      threshold. RESULTS: In the first postoperative year, patients without recurrent
      disease had normal levels of CEA (1.5 +/- 0.9 microg/L) and monoclonal tissue
      polypeptide antigen-M (TPA-M, 64.4 +/- 47.8 U/L), while patients with recurrences
      had high levels of CEA (6.9 +/- 9.8 microg/L, P < 0.01) and TPA-M (192.2 +/-
      328.8 U/L, P < 0.05). During the second postoperative year, patients without
      tumor recurrence had normal levels of CEA (2.0 +/- 1.8 microg/L) and TPA-M (50.8
      +/- 38.4 U/L), while patients with recurrence had high levels of CEA (66.3 +/-
      130.8 microg/L, P < 0.01) and TPA-M (442.7 +/- 652.8 U/L, P < 0.05). The mean
      follow-up time was 22.3 mo. There was recurrence in 23 cases. Five reoperations
      were performed without achieving radical excision. Rises in tumor marker levels
      preceded identification of recurrences: CEA in seven (30%) and TPA-M in eleven
      individuals (48%). CONCLUSION: Intensive follow-up by serial assay of CEA and
      cytokeratins allows early detection of colorectal neoplasm recurrence.

PMID- 16804978
TI  - Interaction between enteric epithelial cells and Peyer's patch lymphocytes in
      response to Shigella lipopolysaccharide: effect on nitric oxide and IL-6 release.
AB  - AIM: To investigate the effect of interaction between enteric epithelial cells
      and lymphocytes of Peyer's patch on the release of nitric oxide (NO) and IL-6 in
      response to Shigella lipopolysaccharide (LPS). METHODS: Human colonic epithelial
      cells (Caco-2) were mixed cocultured with lymphocytes of Peyer's patch from wild
      type (C57 mice) and inducible NO synthase knockout mice, and challenged with
      Shigella F2a-12 LPS. Release of NO and mIL-6 was measured by Griess colorimetric
      assay and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: In
      the absence of LPS challenge, NO was detected in the culture medium of Caco-2
      epithelial cells but not in lymphocytes of Peyer's patch, and the NO release was
      further up-regulated in both cocultures with lymphocytes from either the wild
      type or iNOS knockout mice, with a significantly higher level observed in the
      coculture with iNOS knockout lymphocytes. After Shigella F2a-12 LPS challenge for
      24-h, NO production was significantly increased in both Caco-2 alone and the
      coculture with lymphocytes of Peyer's patch from the wild-type mice but not from
      iNOS knockout mice. LPS was found to stimulate the release of mIL-6 from
      lymphocytes, which was suppressed by coculture with Caco-2 epithelial cells. The
      LPS-induced mIL-6 production in lymphocytes from iNOS knockout mice was
      significantly greater than that from the wild-type mice. CONCLUSION: Lymphocytes
      of Peyer's patch maintain a constitutive basal level of NO production from the
      enteric epithelial cell Caco-2. LPS-induced mIL-6 release from lymphocytes of
      Peyer's patch is suppressed by the cocultured epithelial cells. While no changes
      are detectable in NO production in lymphocytes from both wild-type and iNOS
      knockout mice before and after LPS challenge, NO from lymphocytes appears to play
      an inhibitory role in epithelial NO release and their own mIL-6 release in
      response to LPS.

PMID- 16804979
TI  - Deficiency of Adenomatous Polyposis Coli protein in sporadic colorectal adenomas
      and its associations with clinical phenotype and histology.
AB  - AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli
      (APC) protein and to compare the APC status with the characteristics of
      colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was
      performed on 118 adenomas and the results were compared with parameters of
      malignant potential, location of adenomas, macroscopic appearance and age of the
      patients. RESULTS: A complete loss of the APC protein was found in 28 (24%)
      adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 +/
      14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 +/- 15.5 mm (95% CI 7.8
      19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no
      difference between APC-positive and negative adenomas as to the histological type
      (P = 0.327) and grade of dysplasia (P = 0.494). We found that even advanced
      adenomas did not differ in their APC status from the non-advanced tumors (P =
      0.414). Finally, no difference was found when the location (P = 0.157),
      macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed
      and compared between both APC positive and negative adenomas. CONCLUSION: Most
      adenomas expressed full-length APC protein, suggesting that protein expression is
      not a reliable marker for assessment of APC gene mutation. Complete loss of APC
      protein did not influence morphology, location, or appearance of adenomas, nor
      was it affected by the patient's age.

PMID- 16804980
TI  - How much helpful is the capsule endoscopy for the diagnosis of small bowel
      lesions?
AB  - AIM: To assess the practically usefulness and diagnostic yield of this new method
      in a group of patients with suspected small bowel lesions. METHODS: Capsule
      endoscopic (CE) examination by using M2A capsule endoscope TM (Given Imaging,
      Yoqneam, Israel) was performed in thirty nine patients (26 males, 13 females)
      with suspected small intestinal lesions. The composing of the patients was as
      follows: obscure gastrointestinal bleeding in twenty three patients, known
      Crohn's disease in 6 patients, in whom CE was used to evaluate the severity and
      extension of the diseases, chronic diarrhea in 8 patients, abdominal pain in one
      patient and malignancy in one patient with unknown origin. RESULTS: In two
      patients CE failed. Different abnormalities were revealed in 26 patients overall.
      Detection rate of abnormalities was highest among patients with obscure
      gastrointestinal bleeding and the source of bleeding was demonstrated in 17 of 23
      patients with obscure bleeding (73.9%). Entero-Behcet was diagnosed in two
      patients by CE as a source of obscure gastrointestinal bleeding. In 6 patients
      with known Crohn's disease, CE revealed better evaluation of the disease
      extension. In 3 of 8 (37.5%) patients with chronic diarrhea; CE revealed some
      mucosal abnormalities as the cause of chronic diarrhea. In a patient with
      unexplained abdominal pain and in a cancer patient with unknown origin, CE
      examination was normal. CONCLUSION: In our relatively small series, we found that
      capsule endoscopy is a useful diagnostic tool particularly in diagnosis of
      obscure gastrointestinal bleeding, chronic diarrhea and in estimating the
      extension of Crohn's disease.

PMID- 16804981
TI  - Circulating DNA level is negatively associated with the long-term survival of
      hepatocellular carcinoma patients.
AB  - AIM: To quantify the circulating DNA in plasma from patients with hepatocellular
      carcinoma (HCC) and to evaluate its prognostic value. METHODS: Blood samples were
      collected from 79 patients with HCC before operation, 20 patients with liver
      cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma
      and quantified. The association between circulating DNA level and prognosis of
      HCC patients was evaluated. RESULTS: Compared with the healthy volunteers (17.6
      +/- 9.5 ng/mL), a significant higher circulating DNA level was found in the
      patients with HCC (47.1 +/- 43.7 ng/mL, P = 0.000) or with liver cirrhosis (30.0
      +/- 13.3 ng/mL, P = 0.002). The circulating DNA level was closely associated with
      tumor size (P = 0.008) and TNM stage (P = 0.040), negatively associated with the
      3-year disease-free survival (DFS) (P = 0.017) and overall survival (OS) (P =
      0.001). CONCLUSION: Large or invasive tumor may release more circulating DNA, and
      higher level of circulating DNA may be associated with poor prognosis of HCC
      patients.

PMID- 16804982
TI  - Eradication of H pylori infection in a rural population: one-day quadruple
      therapy versus 7-day triple therapy.
AB  - AIM: To compare the one-day quadruple therapy with a standard 7-d triple therapy
      for H pylori eradication in a rural population of China. METHODS: A total of 396
      patients with (13)C-urea breath test positive for H pylori were assigned into two
      groups: 239 patients received one-day quadruple therapy (amoxicillin 2000 mg qid;
      metronidazole 500 mg qid; bismuth citrate 900 mg qid and lansoprazole 60 mg once
      daily) and 157 patients received 7-d standard triple therapy (amoxicillin 1000 mg
      bid; clarithromycin 500 mg bid and lansoprazole 30 mg bid). All the patients
      underwent a (13)C-UBT to assess the eradication of H pylori infection six weeks
      after treatment. RESULTS: Two hundred and twenty-nine patients completed the one
      day therapy (95.8%) and 148 patients completed the 7-d therapy (94.2%). The one
      day therapy eradicated H pylori infection in 64 patients (27.95%). In contrast,
      103 patients (69.59%) were H pylori negative after the 7-d therapy (P < 0.01).
      CONCLUSION: This pilot study suggests there is no beneficial effect of the one
      day therapy in treatment of H pylori infection compared with the 7-d standard
      therapy.

PMID- 16804983
TI  - Significance of serum IgA in patients with acute hepatitis E virus infection.
AB  - AIM: To study the significance of serum anti-hepatitis E virus (HEV) IgA in
      patients with hepatitis E. METHODS: A new method was established to assay anti
      HEV IgA, which could be detected in the middle phase of the infection. We
      compared anti-HEV IgA assay with anti-HEV IgM and anti-HEV IgG assay in sera from
      60 patients with positive HEV-RNA. RESULTS: The 60 patients with positive HEV-RNA
      had both anti-HEV IgA and anti-HEV IgM and 410 patients with negative HEV-RNA
      were used as control. Periodic serum samples obtained from 60 patients with
      hepatitis E were tested for HEV RNA, anti-HEV IgM, anti-HEV IgA and anti-HEV IgG.
      Their HEV-RNA was detectable in the serum until 20 +/- 11 d. We used anti-HEV IgM
      and anti-HEV IgA assay to detect HEV infection and positive results were found in
      90 +/- 15 d and 120 +/- 23 d respectively, the positive rate of anti-HEV IgA was
      higher than that of anti-HEV IgM and HEV-RNA (P < 0.05). CONCLUSION: The duration
      of anti-HEV IgA in serum is longer than that of anti-HEV IgM, and anti-HEV IgA
      assay is a good method to detect HEV infection.

PMID- 16804984
TI  - Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver
      injury in rats.
AB  - AIM: To study the effects of extract from Ginkgo biloba (EGb) containing 22%
      flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats
      induced by carbon tetrachloride (CCl(4)). METHODS: All rats were randomly divided
      into control group, CCl(4)-treated group, colchicine-treated group and EGb
      protected group. Chronic liver injury was induced in experimental groups by
      subcutaneous injection of CCl(4) and fed with chows premixed with 79.5% corn
      powder, 20% lard and 0.5% cholesterol (v/v). EGb-protected group was treated with
      EGb (0.5 g/kg body weight per day) for 7 wk. At the end of wk 8, all the rats
      were killed. Liver function, liver fibrosis, oxidative stress and expression of
      transforming growth factor beta1 (TGF-beta1), a-smooth muscle actin (alpha-SMA)
      and type I collagens in liver were determined. In addition, pathology changes of
      liver tissue were observed under light microscope. RESULTS: The levels of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (Alb) in EGb
      protected group were notably improved as compared with the CCl(4)-treated group
      (P < 0.01). The contents of serum hyaluronic acid (HA), type III procollagen
      (PCIII), type IV collagen (CIV) and the expression of hepatic tissue TGF-beta1,
      alpha-SMA and type I collagen in EGb-protected group were significantly lower
      than those in CCl(4)-treated groups (P < 0.05, P < 0.01). The degrees of liver
      fibrosis in EGb-protected groups were lower than those in CCl(4)-treated groups
      (6.58 +/- 1.25 vs 9.52 +/- 2.06, P < 0.05). Compared to the CCl(4)-treated group,
      the levels of plasma glutathoine peroxidase (Se-GSH-Px), superoxide dismutase
      (SOD) and malondialdehyde (MDA) were strikingly improved also in EGb-protected
      group (P < 0.05, P < 0.01). CONCLUSION: EGb resists oxidative stress and thereby
      reduces chronic liver injury and liver fibrosis in rats with liver injury induced
      by CCl(4).

PMID- 16804985
TI  - Functional studies of a novel oncogene TGM3 in human esophageal squamous cell
      carcinoma.
AB  - AIM: To investigate the role of transglutaminase 3 (TGM3) gene in human
      esophageal squamous cell carcinoma (ESCC), and analyze its relationship with
      clinicopathological parameters. METHODS: Gene expression of TGM3 in fresh
      esophageal cancer tissues and their corresponding normal mucosas 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 10.0. RESULTS: Expression
      rate of TGM3 was reduced to 81.8% in ESCC. Expression of TGM3 was significantly
      inversely correlated with histological grade of esophageal carcinoma (in grade I,
      II and III tumors, the reduced expression was 4/7, 57/71, and 20/21,
      respectively, P < 0.05), whereas it had no obvious correlations with lymph node
      metastasis and depth of invasion. CONCLUSION: Reduced expression of TGM3 may play
      an important role in esophageal carcinogenesis.

PMID- 16804986
TI  - Mesenteric adenitis caused by Yersinia pseudotubercolosis in a patient
      subsequently diagnosed with Crohn's disease of the terminal ileum.
AB  - Although the association between inflammatory bowel disease and gastrointestinal
      infections has been suggested, the mechanisms involved in the pathogenesis of
      Crohn's disease (CD) are still undetermined. We report the case of a man, who
      presented with mesenteric adenitis initially due to a Yersinia pseudotubercolosis
      infection, who was later diagnosed with Crohn's disease. This case is in keeping
      with recent evidence in the literature which suggests that CD is a disease linked
      to abnormal immune responses to enteric bacteria in genetically susceptible
      individuals.

PMID- 16804987
TI  - Actively bleeding Dieulafoy's lesion of the small bowel identified by capsule
      endoscopy and treated by push enteroscopy.
AB  - Dieulafoy's lesion is an unusual cause of recurrent GI bleeding. This report
      describes a case of actively bleeding Dieulafoy's lesion of the small bowel in
      which the diagnosis was made by capsule endoscopy, followed by treatment with the
      use of push enteroscopy. The case illustrates that capsule endoscopy and
      enteroscopy are highly complementary in patients with small bowel diseases.

PMID- 16804988
TI  - Recurrence of inflammatory pseudotumor in the distal bile duct: lessons learned
      from a single case and reported cases.
AB  - Inflammatory myofibroblastic tumors (IMTs) or inflammatory pseudotumors (IPs)
      have been extensively discussed in the literature. They are usually found in the
      lung and upper respiratory tract. However, reporting of cases involving the
      biliopancreatic region has increased over recent years. Immunohistochemical study
      of these lesions limited to the pancreatic head or distal bile duct seems to be
      compatible with those observed in a new entity called autoimmune pancreatitis,
      but usually intense fibrotic reaction (zonation) predominates producing a mass.
      When this condition is limited to the pancreatic head, the common bile duct might
      be involved by the inflammatory process and jaundice may occur often resembling
      adenocarcinoma of the pancreas. We have previously reported a case of IMT arising
      from the bile duct associated with autoimmune pancreatitis which is an extremely
      rare entity. Four years after Kaush-Whipple resection, radiological examination
      on routine follow-up revealed a tumor mass, suggesting local recurrence.
      Ultrasound-guided FNA confirmed our suspicious diagnosis. This present case, as
      others, suggests that persistent follow-up is necessary in order to prevent
      irreversible liver damage at this specific location.

PMID- 16804989
TI  - Neuroendocrine gastric carcinoma expressing somatostatin: a highly malignant,
      rare tumor.
AB  - Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve
      particular attention, as they are aggressive and have an extremely poor
      prognosis. In this report we describe a gastric neuroendocrine carcinoma with
      rapidly fatal outcome. Immunohistological staining of the resected specimens
      revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense
      immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin
      immunoreactivity. There were no psammoma bodies and no demonstrable association
      with von Recklinghausen's neurofibromatosis. In the gastrointestinal tract,
      neuroendocrine tumors producing predominantly somatostatin have been described
      only in the duodenum. To the best of our knowledge, the present report is the
      second case report of a neuroendocrine gastric carcinoma expressing diffusely
      somatostatin as the only neuroendocrine regulatory peptide.

PMID- 16804990
TI  - Resolution of an intense sweetener mixture by use of a flow injection sensor with
      on-line solid-phase extraction. Application to saccharin and aspartame in sweets
      and drinks.
AB  - An integrated solid-phase spectrophotometry-FIA method is proposed for
      simultaneous determination of the mixture of saccharin (1,2-benzisothiazol-3(2H)
      one-1,1-dioxide; E-954) (SA) and aspartame (N-L-alpha-aspartyl-L-phenylalanine-1
      methyl ester; E-951) (AS). The procedure is based on on-line preconcentration of
      AS on a C18 silica gel minicolumn and separation from SA, followed by
      measurement, at lambda = 210 nm, of the absorbance of SA which is transiently
      retained on the adsorbent Sephadex G-25 placed in the flow-through cell of a
      monochannel FIA setup using pH 3.0 orthophosphoric acid-dihydrogen phosphate
      buffer, 3.75x10(-3) mol L(-1), as carrier. Subsequent desorption of AS with
      methanol enables its determination at lambda = 205 nm. With a sampling frequency
      of 10 h(-1), the applicable concentration range, the detection limit, and the
      relative standard deviation were from 1.0 to 200.0 microg mL(-1), 0.30 microg mL(
      1), and 1.0% (80 microg mL(-1), n = 10), respectively, for SA and from 10.0 to
      200.0 microg mL(-1), 1.4 microg mL(-1), and 1.6% (100 microg mL(-1), n = 10) for
      AS. The method was used to determine the amounts of aspartame and saccharin in
      sweets and drinks. Recovery was always between 99 and 101%. The method enabled
      satisfactory determination of blends of SA and AS in low-calorie and dietary
      products and the results were compared with those from an HPLC reference method.

PMID- 16804991
TI  - A rapidly convergent series for calculation of the interaction between two
      similar plane double layers for Na(2)SO(4) type asymmetric electrolytes at
      positive surface potential.
AB  - A rapidly convergent series for calculation of the interaction energies between
      two similar plane double layers for Na(2)SO(4) type asymmetric electrolytes at
      positive surface potential was obtained by introducing a parameter lambda into an
      elliptical integral. When the dimensionless surface potential is less or equal to
      20, the number of the series terms required to obtain the interaction energies
      with six significant digits is not more than 2. The accurate numeral results were
      given and they can be used to check up the validity of approximate expressions
      obtained. The present results are also fit for CaCl(2) type asymmetric
      electrolytes at negative surface potential.

PMID- 16804992
TI  - [Publications for rheumatology in new forms. What will come--what will remain?].

PMID- 16804993
TI  - [Introduction to the topic: infections in rheumatology].

PMID- 16804994
TI  - [What opportunities are afforded by enzyme replacement therapy].

PMID- 16804995
TI  - [The speciality of rheumatology is on the right path in the G-DRG treatment
      reimbursement system].

PMID- 16804996
TI  - [Giant cell arteritis: the story].

PMID- 16804997
TI  - [Secondary polychondritis in Wegner's disease].

PMID- 16804998
TI  - [Therapy for Reynaud syndrome].

PMID- 16804999
TI  - TMA wins Aetna payment of disputed E&M modifiers.

PMID- 16805000
TI  - Correction: Applicability for Standard MM.3.20, element of performance 13.

PMID- 16805001
TI  - Scaling up HIV testing: human rights and hidden costs.
AB  - The calls for provider-initiated routine HIV testing are growing more intense. In
      this article, Joanne Csete and Richard Elliott discuss the human rights and
      ethical issues raised by the routine testing approach. Some points in this paper
      are inspired by an international expert meeting on HIV testing and human rights
      convened by the Center for Health and Gender Equity, Gay Men's Health Crisis and
      the Canadian HIV/AIDS Legal Network in Montreal in October 2005. The meeting was
      attended by academic experts, UN officials, activists and people living with
      HIV/AIDS from around the world.

PMID- 16805002
TI  - Health Canada authorizes access to experimental HIV drugs, but only after a long
      struggle.
AB  - Five men living with HIV/AIDS, who had developed resistance to conventional
      antiretroviral therapies and who were seriously ill, have finally obtained access
      to two experimental antiretroviral drugs.

PMID- 16805003
TI  - Question period: how will Canada's new minority government approach HIV/AIDS?

PMID- 16805004
TI  - HIV-positive woman suing police, man who allegedly infected her and his family.
AB  - By statement of claim dated 18 April 2005, a Windsor woman is suing a man she
      alleges infected her with HIV. She is also suing the Windsor Police Service and
      the man's family.

PMID- 16805005
TI  - Medical marijuana users continue to experience legal barriers.
AB  - Four recent developments highlight that people continue to face significant legal
      and administrative barriers to using marijuana for medical purposes--despite the
      existence of the Marihuana Medical Access Regulations (MMAR), enacted by the
      federal government, as a result of court rulings, to enable people who require
      marijuana for medical purposes to exercise their constitutional right to such
      medicine.

PMID- 16805006
TI  - New developments in mandatory blood testing legislation.
AB  - In November 2005, the Liberal government in Ontario introduced a bill that would
      allow policy officers, other community safety workers and victims of crime to
      find out more quickly whether they have been exposed to infection from certain
      viruses. Meanwhile, the Saskatchewan Medical Association (SMA) is opposing
      similar legislation enacted in that province.

PMID- 16805007
TI  - Health care workers push for use of safer hypodermic needles.
AB  - Unions in Ontario and British Columbia representing nurses and other health care
      workers are lobbying for safer hypodermic needles in hospitals, long-care
      facilities and other medical settings.

PMID- 16805008
TI  - Vancouver safe injection facility: more positive results.
AB  - Two recently published articles report on the positive impact of Insite on drug
      use among people who inject drugs.

PMID- 16805009
TI  - Gay man launches suit over refusal to accept blood donation.
AB  - Adrian Lomaga, a McGill law student who is gay, is suing Hema-Quebec because it
      refuses to accept his blood donation. Hema-Quebec, which is the blood collection
      agency for the province, imposes a lifetime ban on blood donations from men who
      have had sex with another man even once since 1977. The Canadian Blood Services
      has the same policy.

PMID- 16805010
TI  - Vancouver police crack down on drug users, safe injection facility.

PMID- 16805011
TI  - WTO approves TRIPS amendment on importing under compulsory licensing.
AB  - On 6 December 2005, the World Trade Organization (WTO) amended the Trade Related
      Aspects of Intellectual Property Rights (TRIPS) agreement to allow WTO member
      states to produce, under compulsory licences, lower-cost generic pharmaceutical
      products for export to countries that lack domestic production capacity to make
      such products. The amendment makes permanent the previous decision of 30 August
      2003, which has not yet proven to be an effective mechanism to encourage the
      supply of more affordable medicines and other pharmaceutical products to
      countries in need.

PMID- 16805012
TI  - Who killed HIV/AIDS activist Steve Harvey?
AB  - On 30 November 2005, Jamaican HIV/AIDS activist Steve Harvey was found murdered.
      Harvey was a staunch defender of the human rights of people living with, and
      vulnerable to, HIV/AIDS. Since 1997, he had worked at Jamaica AIDS Support. In
      this commentary, Garry Mullins examines the deep roots and social acceptance of
      homophobia, and its consequences, in Jamaican society.

PMID- 16805013
TI  - Thais protest US-Thai FTA talks.
AB  - On 11 January 2006, thousands of Thai citizens and HIV/AIDS advocacy groups
      converged in Chiang Mai, Thailand to protest the latest negotiations of the
      proposed US-Thailand Free Trade Agreement (FTA). The FTA is believed to include
      intellectual property (IP) provisions that will pose a threat to Thailand's
      national HIV/AIDS treatment program, which relies on local production of
      inexpensive generic medicines to treat people living with HIV/AIDS.

PMID- 16805014
TI  - Lesotho embarks on universal HIV testing.
AB  - On 1 December 2005, this past World AIDS Day, Lesotho embarked on the "Know Your
      Status" initiative to provide country-wide voluntary counselling and testing
      (VCT) for HIV/AIDS. In a country of two million people with a 29 percent HIV
      infection rate, the universal testing initiative may help prevent a humanitarian
      and economic crisis capable of destroying the country. However, the initiative
      raises human rights concerns.

PMID- 16805015
TI  - CEE/CA: Report calls for decriminalization of sex work.
AB  - In December 2005, the Central and Eastern European Harm Reduction Network
      (CEEHRN) released a report calling for the decriminalization of sex work in the
      27 countries of Central and Eastern Europe and Central Asia (CEE/CA). The report
      brings together a wealth of published and original information concerning sex
      work, laws regulating sex work, epidemiological data regarding HIV and other
      sexually transmitted infections (STIs), services available to sex workers, and
      human rights abuses faced by sex workers.

PMID- 16805016
TI  - UK: legal action launched against government's guidelines on non-occupational
      post-exposure prophylaxis.
AB  - In December 2005, two gay men were granted legal aid on public interest grounds
      by the Legal Services Commission to take the UK Department of Health to court
      over its policy regarding non-occupational post-exposure prophylaxis for HIV
      (NPEP).

PMID- 16805017
TI  - Lithuania: Legal Network meeting discusses model legislation project.
AB  - On 7-8 November 2005, the Legal Network held a meeting in Vilnius, Lithuania as
      part of its model legislation project.

PMID- 16805018
TI  - Russian Federation: Duma repeals Russian Criminal Code reforms.

PMID- 16805019
TI  - UK: Home Office announces new policy initiative on prostitution.

PMID- 16805020
TI  - UK: groups call for comprehensive response to HIV and hepatitis in prison.

PMID- 16805022
TI  - Namibia: anti-homosexuality law undermines HIV prevention in prisons.

PMID- 16805021
TI  - Australia: ACT considers prison needle exchange program.

PMID- 16805023
TI  - India: UNAIDS claims law criminalizing homosexuality hinders HIV prevention.

PMID- 16805024
TI  - Supreme Court clarifies immigration medical inadmissibility provision.
AB  - On 21 October 2005, the Supreme Court of Canada released a decision directing
      immigration authorities to consider an applicant's financial circumstances when
      determining whether the applicant's dependant with a mental and physical
      disability will place "excessive demand" on social services in Canada. However,
      the potential impact of the decision upon the situation of people living with
      HIV/AIDS applying for permanent residence status is unclear.

PMID- 16805025
TI  - Federal health information privacy cases from 2005.
AB  - The federal Personal Information Protection and Electronics Documents Act
      (PIPEDA) governs the collection, use and disclosure of personal information.
      PIPEDA is important legislation for people living with HIV/AIDS as it establishes
      rules for the handling of personal information, including personal health
      information. PIPEDA applies to personal information handled by commercial
      enterprises in the course of commercial activities throughout Canada, except in
      provinces that have significantly similar laws. Complaints under PIPEDA are heard
      by the Privacy Commissioner of Canada (PC). This article reviews the
      interpretation and application of PIPEDA in complaints related to health
      information decided in 2005.

PMID- 16805026
TI  - Criminal law and HIV transmission/exposure: five new cases.

PMID- 16805027
TI  - UK: Court of Appeals upholds deportation orders of four people with HIV.
AB  - In November 2005, the UK Court of Appeals upheld deportation orders against four
      people with HIV who claimed that removal to their home countries, where they
      would be unable to obtain treatment, violated the rights to privacy and to be
      free from inhuman treatment under the European Convention on Human Rights. The
      Court of Appeal affirmed that only in exceptional circumstances could persons
      with HIV rely on the European Convention to avoid deportation. None of the
      applicants' circumstances were found to be exceptional. The decision reflects the
      UK courts' narrow approach to interpretation of the Convention, an interpretation
      that makes it unlikely that the vast majority of persons living with HIV/AIDS
      will be able to successfully challenge deportation orders even when they face
      illness and death if expelled.

PMID- 16805028
TI  - India: exclusion of people with HIV from police force unconstitutional,
      administrative tribunal holds.

PMID- 16805029
TI  - Australia: Court recognizes that HIV-positive people face special challenges in
      prison.
AB  - An Australian appellate court granted bail to a man charged with two separate
      counts of endangering life for allegedly having unprotected sex with two partners
      without disclosing that he was HIV positive. The man, who has pleaded not guilty
      to both charges, is accused of having committed the second offence while he was
      released on bail awaiting trial for the first. In deciding to release him, the
      Court considered, among other things, the unique difficulties that people living
      with HIV/AIDS face in prisons.

PMID- 16805030
TI  - US: Kansas court strikes down harsher penalty for gay underage sex.
AB  - In October 2005, the Kansas Supreme Court struck down a law that would impose
      harsher penalties for same-sex statutory rape cases than for heterosexual cases.
      In arriving at its conclusion that the distinction had no rational basis, the
      Court noted that gay teenage sex is no more likely than adult or heterosexual sex
      to result in HIV transmission.

PMID- 16805031
TI  - Criminal law and HIV/AIDS: four new cases.

PMID- 16805032
TI  - Australia: HIV-positive applicant for permanent residence obtains waiver of
      medical inadmissibility.

PMID- 16805033
TI  - UK:  House of Lords refuses leave to appeal HIV transmission conviction.

PMID- 16805034
TI  - Aboriginal and Torres Strait Islander participation in ethical review of health
      research.

PMID- 16805035
TI  - [On guard! Representations of tuberculosis in Quebec during the first half of the
      20th century. (Review of: Cote, L. En garde! Les representations de la
      tuberculose au Quebec dans la premiere moitie du XXe siecle. Quebec: Pr. de l'U.
      Laval, 2000)].

PMID- 16805036
TI  - [Coverage of smoking cessation by National Insurance policy].

PMID- 16805037
TI  - A social contract for the coal fields: the rise and fall of United Mine Workers
      of America Welfare and Retirement Fund.  [Review of: Mulcahy, R.P.  A social
      contract for the coal fields: the rise and fall of United Mine Workers of America
      Welfare and Retirement Fund.  Knoxville: U. of Tennessee Pr., 2000].

PMID- 16805038
TI  - Science, race, and religion in the American South: John Bachman and the
      Charleston Circle of naturalists, 1815-1895.  [Review of: Stephens, L.D. 
      Science, race, and religion in the American South: John Bachman and the
      Charleston Circle of naturalists, 1815-1895.  Chapel Hill: U. of North Carolina
      Pr., 2000].

PMID- 16805039
TI  - The spirit of a place called Meharry: the strength of its past to shape the
      future.  [Review of: Johnson, C.W.  The spirit of a place called Meharry: the
      strength of its past to shape the future.  Franklin, Tenn.: Hillsboro Pr., 2000].

PMID- 16805040
TI  - Bioarchaeological studies of life in the age of agriculture: a view from the
      Southeast.  [Review of: Lambert, P.M., ed.  Bioarchaeological studies of life in
      the age of agriculture: a view from the Southeast.  Tuscaloosa: U. of Alabama
      Pr., 2000].

PMID- 16805041
TI  - Fear Avoidance Beliefs Questionnaire (FABQ).

PMID- 16805042
TI  - Religious freedom and Indian rights: the case of Oregon v. Smith.  [Review of:
      Long, C.N.  Religious freedom and Indian rights: the case of Oregon v. Smith. 
      Lawrence: U. Pr. of Kansas, 2000].

PMID- 16805043
TI  - The Whiplash Disability Questionnaire (WDQ).

PMID- 16805044
TI  - Eye on the cytoplasm.

PMID- 16805045
TI  - The price of a gift: a Lakota healer's story.  [Review of: Mohatt, G. and Eagle
      Elk, J.  The price of a gift: a Lakota healer's story.  Lincoln: U. of Nebraska
      Pr., 2000].

PMID- 16805046
TI  - Drug hypersensitivity--where do we stand?

PMID- 16805047
TI  - Witches of the Atlantic world: a historical reader and primary sourcebook. 
      [Review of: Breslaw, E.G.  Witches of the Atlantic world: a historical reader and
      primary sourcebook.  New York: New York U. Pr., 2000].

PMID- 16805048
TI  - Man and wife in America: a history.  [Review of: Hartog, H.  Man and wife in
      America: a history.  Cambridge, Mass.: Harvard U. Pr., 2000].

PMID- 16805049
TI  - Patient handout: Advance directives.

PMID- 16805050
TI  - Chlamydia trachomatis among antenatal women in Sydney.

PMID- 16805051
TI  - Orthopaedic proceedings, 2005, 2006.

PMID- 16805052
TI  - Abstracts of the 2006 In Vitro Biology Meeting, Minneapolis, Minnesota, USA, June
      3-7, 2006.

PMID- 16805053
TI  - [Study report: Hypertension therapy with organ protection. Piretanid and
      Ramipril: advantages with fixed combination].

PMID- 16805054
TI  - Devices and desires: gender, technology, and American nursing.  [Review of:
      Sandelowski, M.  Devices and desires: gender, technology, and American nursing. 
      Chapel Hill: U. of North Carolina Pr.; New York: Hill and Wang, 2000].

PMID- 16805055
TI  - Childhood mortality and nutritional status as indicators of standard of living:
      evidence from World War I recruits in the United States.

PMID- 16805056
TI  - Incentives in the Medicare prescription drug benefit.

PMID- 16805057
TI  - The determinants of mortality.

PMID- 16805058
TI  - "Modern marriage" for African Americans, 1920-1940.

PMID- 16805059
TI  - [Scientific bibliography of the Pomeranian Medical University in Szczecin for
      year 2003].

PMID- 16805060
TI  - American health care: government, market processes, and the public interest. 
      [Review of: Feldman, R.D.  American health care: government, market processes,
      and the public interest.  New Brunswick, N.J.: Transaction, 2000].

PMID- 16805061
TI  - Bodies of inscription: a cultural history of the modern tattoo community. 
      [Review of: DeMello, M.  Bodies of inscription: a cultural history of the modern
      tattoo community.  Durham, N.C.: Duke U. Pr., 2000].

PMID- 16805062
TI  - HAH 2006. Abstracts of the 12th International Conference on Human Antibodies and
      Hybridomas, 10-12 May 2006, Montego Bay, Jamaica.

PMID- 16805063
TI  - Tuberculin skin testing of close contacts: recent or long-standing infection?

PMID- 16805064
TI  - Statement on influenza vaccination for the 2006-2007 season. An Advisory
      Committee Statement (ACS).

PMID- 16805065
TI  - Science, race, and religion in the American South: John Bachman and the
      Charleston Circle of naturalists, 1815-1895.  [Review of: Stephens, L.D. 
      Science, race, and religion in the American South: John Bachman and the
      Charleston Circle of naturalists, 1815-1895.  Chapel Hill: U. of North Carolina
      Pr., 2000].

PMID- 16805066
TI  - Taking the waters in Texas: springs, spas, and fountains of youth.  [Review of:
      Valenza, J.M.  Taking the waters in Texas: springs, spas, and fountains of youth.
      Austin: U. of Texas Pr., 2000].

PMID- 16805067
TI  - Pedigree in the machine: the past and the future of genealogical computing.

PMID- 16805068
TI  - A population history of North America.  [Review of: Haines, M.R. and Steckel,
      R.H., ed.  A population history of North America.  New York: Cambridge U. Pr.,
      2000].

PMID- 16805069
TI  - Ah-ayitaw isi e-ki-kiskeyihtahkik maskihkiy. They knew both sides of medicine:
      Cree tales of curing and cursing told by Alice Ahenakew.  [Review of: Ahenakew,
      A.  Ah-ayitaw isi e-ki-kiskeyihtahkik maskihkiy. They knew both sides of
      medicine: Cree tales of curing and cursing told by Alice Ahenakew.  Winnipeg: U.
      of Manitoba Pr., 2000].

PMID- 16805070
TI  - The father of Canadian psychiatry: Joseph Workman.  [Review of: Johnston, C.I.M. 
      The father of Canadian psychiatry: Joseph Workman.  Victoria, B.C.: Ogden, 2000].

PMID- 16805071
TI  - A measure of value: the story of the D'Arcy Island leper colony.  [Review of:
      Yorath, C.  A measure of value: the story of the D'Arcy Island leper colony. 
      Victoria, B.C.: TouchWood, 2000].

PMID- 16805072
TI  - [The impact of heptral, vitamin B6 and folic acid on the indices of hepatic
      biotransformation in toxic hepatitis].

PMID- 16805073
TI  - Patient-physician harassment.

PMID- 16805074
TI  - Our white coats are not armour. Protecting physicians in the doctor-patient
      relationship.

PMID- 16805075
TI  - Facing death: embracing life.

PMID- 16805076
TI  - Fecal occult blood testing for colorectal cancer screening.

PMID- 16805077
TI  - Stillbirth.

PMID- 16805078
TI  - Paternal use of ribavirin-interferon alpha 2B combination therapy before
      conception.
AB  - QUESTION: One of my male patients is receiving ribavirin-interferon alpha 2B
      (Pegetron) combination therapy for chronic hepatitis C. His wife recently found
      out she is 6 weeks pregnant. They are concerned that the medications might have
      affected his sperm. How should I advise them? ANSWER: To the best of our
      knowledge, paternal exposure to ribavirin-interferon alpha 2B has no adverse
      effects on reproduction. Although we do not have sufficient information to
      confirm this, several pregnancies where the father had been exposed to these
      medications turned out fine. If an unexpected pregnancy occurs while the father
      is receiving this therapy, there is no medical indication for terminating the
      pregnancy.

PMID- 16805079
TI  - Ophthaproblem. Central retinal vein obstruction.

PMID- 16805080
TI  - Anticoagulation for atrial fibrillation.

PMID- 16805081
TI  - Flexible asthma therapy.

PMID- 16805082
TI  - Woman physician stalked. Personal reflection and suggested approach.
AB  - OBJECTIVE: To increase awareness of the stalking and harassing behaviour
      physicians sometimes encounter from patients and to explore how best to approach
      and address this behaviour. SOURCES OF INFORMATION: A physician's personal
      reflection of a stalking incident is combined with a review of the literature.
      Few studies have addressed this subject. MAIN MESSAGE: Any family physician could
      be the victim of stalking. Physicians' routines and schedules are often public
      knowledge because of their availability to their practices; thus they are
      particularly vulnerable to stalkers. We rarely think of women stalking female
      family physicians; however, it is likely more common than we realize. Increased
      awareness of this phenomenon and appropriate interventions could reduce
      escalation of harassing behaviour. Helpful strategies could include recognizing
      and addressing the behaviour early, seeking assistance, and documenting all
      incidents in a separate file that includes tape recordings or other material.
      CONCLUSION: We should explore stalking and harassing behaviour openly and become
      aware of the risks so that we can identify appropriate strategies to avert
      problems and deal with stalkers.

PMID- 16805083
TI  - Integrating nutrition services into primary care: Experience in Hamilton, Ont.
AB  - PROBLEM BEING ADDRESSED: Nutrition services can have an important role in
      prevention and management of many conditions seen by family physicians, but
      access to these services in primary care is limited. OBJECTIVE OF PROGRAM: To
      integrate specialized nutrition services into the offices of family physicians in
      Hamilton, Ont, in order to improve patient access to those services, to expand
      the range of problems seen in primary care, and to increase collaboration between
      family physicians and registered dietitians. PROGRAM DESCRIPTION: Registered
      dietitians were integrated into the offices of 80 family physicians. In
      collaboration with physicians, they assessed, treated, and consulted on a variety
      of nutrition-related problems. A central management team coordinated the
      dietitians' activities. CONCLUSION: Registered dietitians can augment and
      complement family physicians' activities in preventing, assessing, and treating
      nutrition-related problems. This model of shared care can be applied to
      integrating other specialized services into primary care practices.

PMID- 16805084
TI  - Case report: osteogenesis imperfecta Elusive cause of fractures.

PMID- 16805085
TI  - Nurse practitioners and physician attrition.

PMID- 16805086
TI  - Nurse practitioners: Working with family physicians to improve access.

PMID- 16805087
TI  - Role of CD4+ T cells in a protective immune response against Cryptococcus
      neoformans in the central nervous system.
AB  - Cryptococcosis is a life-threatening disease caused by the encapsulated yeast,
      Cryptococcus neoformans. Although infection with C. neoformans is initiated in
      the lungs, morbidity and mortality is mostly associated with infections of the
      central nervous system (CNS). Individuals with deficiencies in cell-mediated
      immunity, such as patients with AIDS, are more susceptible to disseminated
      cryptococcosis, highlighting the importance of cell-mediated immunity and CD4+ T
      cells in host resistance against C. neoformans. Using a mouse model of
      cryptococcal meningoencephalitis, we have shown that immunization of mice with a
      cryptococcal antigen induced a protective immune response that crossed the blood
      brain barrier and initiated an immune response directly in the CNS if C.
      neoformans was present. The regional protective response was characteristic of a
      Type-1 (Th1) response in the types of cells present at the site of infection and
      in the cytokines and chemokines expressed. Here, we extend those findings and
      report that CD4+ T cells are required for survival of immune mice infected
      directly in the brain with C. neoformans and sensitized CD4 + T cells can
      transfer partial protection to naive mice infected intracerebrally with C.
      neoformans. Furthermore, CD4 + T cells were also important for optimal
      infiltration of inflammatory cells at the site of infection and in the expression
      of cytokines and chemokines associated with protection in the brain. Lastly, CD4+
      T cells were required for optimal regional production and secretion of IFNgamma
      and in the significantly increased expression of iNOS in C. neoformans-infected
      brains of immune mice.

PMID- 16805088
TI  - A case of imported paracoccidioidomycosis: an awkward infection in The
      Netherlands.
AB  - Paracoccidioidomycosis is an important endemic mycosis in South America. In
      Europe the disease is very rare and only found as infections in travelers to
      Latin America. We report here the first case encountered in the Netherlands for
      which the appropriate diagnosis was not attained for several months. A Dutch 60
      year-old man presented with a painful ulceration in the buccal mandibular
      vestibular mucosa of three months duration. While his medical history was
      uneventful, he had worked, until 8 years prior to his presentation, as a
      carpenter for 25 years in the jungles of Peru and Ecuador. An aberrant chest
      radiograph, CT-scan of the lungs and increased erythrocyte sedimentation rate
      were suggestive of sarcoidosis or a bronchiolitis obliterans organizing
      pneumonia. There was no improvement in the patient's symptoms despite the use of
      budesonide and prednisone medication, as well as tuberculosis prophylaxis with
      isoniazide and rifampicin, and local use of miconazole. Quite to the contrary, as
      an irritated, irregular hyperemic mucosa and gingiva with ulceration were noticed
      during this period of time. These precipitated an incisional biopsy through which
      a mixed inflammatory cellular infiltrate and large yeast cells were found on
      histopathologic examination. Based on the patient's travel history and the
      multiple budding yeastlike cells revealed in the biopsy tissue, the diagnosis of
      paracoccidioidomycosis was finally made. This was supported by the isolation of
      Paracoccidioides brasiliensis in culture. Antimycotic oral therapy with
      itraconazole was started and continued for 15 months. At two and five year follow
      ups, the patient was asymptomatic. In Europe, it may be expected that diseases
      that are endemic in other areas will be seen more frequently in countries where
      the diseases are not routinely encountered. It is most likely that the use of
      corticosteroid medication, with its inherent immunosuppressive effect, resulted
      in the reactivation of an infection acquired many years before in Latin America.
      The etiologic agent then disseminated from the initial focal point to cause the
      ensuing oral mucous membrane lesions. The importance of the patient's prolonged
      residence in Latin America was overlooked. The very long latency of endemic
      mycoses emphasizes the need for a meticulous history which should include not
      only recent trips, but also past residence in foreign countries.

PMID- 16805089
TI  - Diagnostic challenge of zygomycosis in compromised hosts.
AB  - Rhinocerebral zygomycosis was classically associated with diabetes and diabetic
      ketoacidosis in the past. In recent years, hematological malignancies and
      immunocompromised states have become increasingly more frequent underlying
      conditions for patients with pulmonary and disseminated zygomycosis. In this
      study we identified 37 patients with a histopathologic diagnosis of zygomycosis
      and 21 patients with a positive culture for zygomycetes seen at the National
      Taiwan University Hospital, Taipei, during 1986-2003. Of these, 39 cases with
      probable or proven invasive zygomycosis were included in these studies. The major
      underlying diseases were immunocompromised states (74%), and diabetes mellitus
      (26%). The frequency of zygomycosis in immunocompromised hosts increased from
      1.86 during 1986-1991 to 4.13 per 100,000 discharges during 1998-2003.
      Rhinocerebral involvement was the most common site (74%). An antemortem diagnosis
      by sinus biopsy was made in 93.1%. Immunocompromised patients were more likely to
      be younger than diabetics, to have an onset during hospitalization, a positive
      culture and a postmortem diagnosis. They were less likely than patients with
      diabetes to receive surgery and more likely to die in the hospital (p < 0.05). Of
      the 29 patients with invasive rhinocerebral zygomycosis, cerebral involvement
      (adjusted odds ratio [OR]: 31.7, 95% confidence interval [CI]: 2.4-426.8, p =
      0.009) and positive cultures (adjusted OR: 23.8, 95% CI: 1.7-338.6, p = 0.019)
      were associated with in-hospital mortality by multivariate analysis.
      Hematological disease and steroid use have become the most important predisposing
      factors for zygomycosis. Aggressive diagnostic approaches, effective antifungal
      therapy and surgical debridement are essential for a successful outcome.

PMID- 16805090
TI  - Pathogenicity of the Chrysosporium anamorph of Nannizziopsis vriesii for veiled
      chameleons (Chamaeleo calyptratus).
AB  - Veiled chameleons (Chamaeleo calyptratus) were experimentally challenged with the
      fungus Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Chameleons were
      exposed to conidia in their captive environment, or were inoculated by direct
      application of a conidial suspension inoculum on intact and on abraded skin. The
      CANV induced lesions in all experimental groups and was recovered from infected
      animals, fulfilling Koch's postulates and confirming that it may act as a primary
      fungal pathogen in this species of reptile. A breach in cutaneous integrity, as
      simulated by mild scarification, increased the risk of infection but was not
      required for the CANV to express pathogenicity. Initial hyphae proliferation
      occurred in the outer epidermal stratum corneum, with subsequent invasion of the
      deeper epidermal strata and dermis. A spectrum of lesions was observed ranging
      from liquefactive necrosis of the epidermis to granulomatous inflammation in the
      dermis. CANV dermatomycosis appears to be contagious and can readily spread
      within a reptile collection, either directly through contact with infective
      arthroconidia or indirectly via fomites. Dense tufts of arthroconidiating hyphae
      were demonstrated histologically on the skin surface of many animals that
      developed dermatomycosis, and these arthroconidia may act as infective propagules
      involved in the transfer of disease between reptiles.

PMID- 16805091
TI  - Polycytella hominis is a mutated form of Scedosporium apiospermum.
AB  - PCR amplification and sequencing of two separate regions of the nuclear ribosomal
      repeat region revealed that Polycytella hominis, a hyphomycete isolated from a
      human case of mycetoma, was genetically indistinguishable from Scedosporium
      apiospermum (the anamorph of Pseudallescheria boydii). These organisms also
      exhibited remarkably similar susceptibility profiles to common antifungal agents.
      P. hominis is thus likely to be a mutant of S. apiospermum showing abnormalities
      of sporulation, for which a possible mechanism is discussed. Polycytella hominis
      should thus be regarded as a synonym of Scedosporium apiospermum.

PMID- 16805092
TI  - Analysis of non-adhesive pathogenic mechanisms of BAD1 on Blastomyces
      dermatitidis.
AB  - The adhesin BAD1 is required for virulence of Blastomyces dermatitidis in a
      pulmonary model of infection. Herein, we explored mechanisms by which BAD1
      enhances pathogenicity of the fungus. Isogenic strains with and without BAD1
      exhibited similar phenotypic differences in virulence by pulmonary and
      intravenous routes of infection, indicating that BAD1 may exert virulence beyond
      adherence to respiratory lining cells. Non-adhesive mechanisms including
      maintenance of intrinsic resistance of yeast against phagocyte responses and
      products were excluded. A shift in the balance of type 1 and 2 cytokines and in
      the cellular profile of the inflammatory response after the first week of
      pulmonary infection was associated with BAD1. By the second week of infection,
      infection with wild-type yeast was associated with less IL-12 and IFN-gamma, and
      more IL-10, and an influx of inflammatory cells rich in neutrophils and poor in T
      cells, when compared to infection with the BAD1 null strain. Taken together with
      previously reported BAD1 perturbations of TNF-gamma and TGF-beta, these data
      suggest that BAD1 contributes significantly to the pathogenicity of B.
      dermatitidis by also deviating host adaptive immunity, and leukocyte responses.

PMID- 16805093
TI  - Susceptibility to pulmonary blastomycosis in young compared to adult mice: immune
      deficiencies in young mice.
AB  - The immunological basis for differences in resistance to pulmonary blastomycosis
      between young (3 to 4-week-old) and adult (7 to 8-week-old) CD-1 mice is unknown.
      We assessed whether there were differences in fungicidal activity of phagocytes
      and Th-1 lymphocyte cytokine production. The fungicidal activity of young
      bronchoalveolar macrophages (BAM) (20%) against Blastomyces dermatitidis (Bd) was
      comparable to killing by adult BAM (25%). However, IFN-gamma enhanced the killing
      by adult BAM (from 30 to 69%) to a greater extent than BAM from young animals
      (from 20 to 30%). Killing of Bd by young peritoneal macrophages (PM) (46%) and
      adult PM (42%) was similar, and the enhancement of cells of both by IFN-gamma was
      similar. TNFalpha production by young macrophages (BAM or PM), when cocultured
      with Bd for 18 h, was half of TNFalpha secreted by adult macrophages. We found
      that polymorphonuclear neutrophils (PMN) from young mice had deficient fungicidal
      activity against Bd (37%) compared with adult PMN (80%). Interferon-gamma (IFN
      gamma) treatment increased PMN killing of Bd by PMN of young animals from 37 to
      80%. In an assessment of innate responses, we found spleen cells from young mice
      produced three-fold less IFN-gamma and three-fold less IL-2 than adult spleen
      cells in response to 1 microg/ml concanavalin A (Con A). The young spleen cells
      also produced more NO, which we demonstrated reduced Con A-induced proliferation.
      These in vitro results demonstrate several immunological deficiencies in cells
      from young mice and these deficiencies correlate with susceptibility. In a pilot
      reconstitution experiment in pulmonary blastomycosis, treatment of infected young
      mice with IFN-gamma (18.5 x 10(3) U, s.c.) on days 0, 1, and 2 significantly
      increased survival.

PMID- 16805094
TI  - Paranasal sinus fungus ball: epidemiology, clinical features and diagnosis. A
      retrospective analysis of 173 cases from a single medical center in France, 1989
      2002.
AB  - Over the last decade, we have observed a high frequency of Aspergillus
      rhinosinusitis in french medical centers. The epidemiological data, clinical
      presentations, radiology, mycology and histology results of 173 consecutive
      patients with paranasal sinus fungus balls who were admitted from 1989 to 2002
      have been reviewed. The most common symptoms included purulent nasal discharges
      and nasal obstructions, with the maxillary sinus being the most common site of
      infection (152 cases, 87.8%). Computed tomography scans (CT scan) were performed
      in 92% (159/173) of the cases and heterogeneous opacities were observed in 132
      patients (83%). Histology examinations were performed in all cases and proved
      positive in 162 patients. Fungi were recovered, mainly Aspergillus fumigatus,
      from samples of 50 patients, while specimens from the remaining 123 patients were
      negative. Since no specific clinical sign could be found, a diagnosis of fungus
      ball is frequently made after a long term symptomatic period. CT scan findings of
      metallic or calcified densities within an opacified sinus cavity are highly
      suggestive of a fungus ball, but mycological and histological studies are
      essential to confirm the diagnosis. Treatment consisted of functional endonasal
      sinus surgery and was successful in 172 out of 173 cases.

PMID- 16805095
TI  - Efficacy of micafungin alone or in combination against experimental pulmonary
      aspergillosis.
AB  - Mortality from invasive pulmonary aspergillosis approaches 80% with few useful
      therapeutic options available. In these studies, we examined the efficacy of
      micafungin (MICA) alone or in combination with other antifungals in a model of
      pulmonary aspergillosis in immunosuppressed DBA/2 mice infected intranasally with
      conidia of Aspergillus fumigatus 10AF. In the initial study, groups of mice were
      given saline, or 1, 3 or 10 mg kg(-1) of MICA b.i.d., s.c. All saline controls,
      and 90% of untreated mice succumbed to infection. The efficacy of MICA was
      difficult to assess because of an apparent toxicity at 10 mg kg(-1). MICA given
      at 1 mg/kg significantly prolonged survival over the saline controls (P = 0.008).
      MICA at 3 or 10 mg kg(-1) versus the saline controls approached significance. No
      treatment regimen differed in efficacy. The efficacy of combination therapy was
      assessed, with mice given either no treatment, MICA at 1 mg/kg/dose, 0.8 mg kg(
      1) of intravenous amphotericin B (AMB), 100 mg kg(-1) of oral itraconazole (ICZ),
      or 100 mg/kg/dose of twice-daily subcutaneous nikkomycin Z (NIK). AMB alone and
      MICA + AMB or MICA +NIK significantly prolonged survival (P < 0.05 - 0.02) over
      that of the controls. ICZ alone, ICZ+MICA and NIK alone did not significantly
      prolong survival. MICA alone at 1 mg/kg approached significance in prolonging
      survival. The combination of MICA and ICZ appeared to be potentially
      antagonistic. Although AMB+MICA was efficacious, no synergistic activity was
      noted for any of the regimens. Overall, these results indicate that MICA has
      moderate activity against pulmonary aspergillosis and might be useful in
      combination with conventional AMB.

PMID- 16805096
TI  - Empyema thoracis due to Rhizopus oryzae in an allogenic bone marrow transplant
      recipient.
AB  - We describe a case of empyema thoracis caused by Rhizopus oryzae diagnosed in an
      allogenic bone marrow transplant patient with acute lymphocytic leukemia. The
      isolate of R. oryzae was recovered from three pleural effusion specimens, which
      were black in color. It was identified on the basis of characteristic colonial
      appearance and microscopic findings, as well as the partial sequencing of rRNA
      genes. The patient died of uncontrolled R. oryzae empyema thoracis and
      concomitant nosocomial infection.

PMID- 16805097
TI  - Inhibition of sodium glucose cotransporter-I expressed in Xenopus laevis oocytes
      by 4-acetoxyscirpendiol from Cordyceps takaomantana (anamorph = Paecilomyces
      tenuipes).
AB  - Cordyceps contains many health-promoting constituents. Recent studies revealed
      that the fruiting body of cordyceps significantly alleviates hyperglycemia which
      usually accompanies diabetes mellitus. The mechanism of the anti-hyperglycemic
      effect by cordyceps, however, is not fully understood. In this study, methanolic
      extracts were prepared from fruiting bodies of Paecilomyces tenuipes, and 4-beta
      acetoxyscirpendiol (ASD) was eventually purified from the extracts. The Na+/
      glucose transporter-1 (SGLT-1) was expressed in Xenopus oocytes, and the effect
      of ASD on it was analyzed using voltage clamp and 2-deoxy-D-glucose (2-DOG)
      uptake studies. Fluorescence microscopy was performed to monitor the effect of
      ASD on glucose uptake using HEK293 cells expressing recombinant SGLT-1. ASD
      inhibited SGLT-1 activity, and its two derivatives (2-acetoxyscirpenol and 15
      acetoxyscirpendiol), were also effective; 15-acetoxyscirepenol was as inhibitory
      as ASD while diacetoxyscirpenol had less effect. Thus, the ASD in P. tenuipes may
      play an important role in lowering blood sugar in the circulatory system along
      with its derivatives as specific inhibitors of SGLT-1.

PMID- 16805098
TI  - Canine sporotrichosis in Rio de Janeiro, Brazil: clinical presentation,
      laboratory diagnosis and therapeutic response in 44 cases (1998-2003).
AB  - A sporotichosis epidemic involving forty-four dogs in the Metropolitan area of
      Rio de Janeiro is described. Solitary skin lesions were noted in 18 dogs (40.9%),
      2-4 such lesions were observed in 17 animals (38.6%), and nine (20.5%) animals
      had five or more lesions. Twenty-five (56.8%) animals had single ulcerated skin
      lesions on the nose and nine (20.5%) showed nasal mucosal involvement (three of
      which also has a skin lesion). Respiratory symptoms were observed in 17 (38.6%)
      dogs and were found to be the most common extracutaneous signs of infection.
      Anemia, leukocytosis with neutrophilia, hypoalbuminemia and hyperglobulinemia
      were the most frequent hematological abnormalities. Histopathological analysis of
      skin biopsies in most cases revealed granulomatous reactions characterized by
      histiocytic hyperplasia and neutrophil infiltration. Yeast-like cells were
      observed in seven (16.7%) of 42 dogs examined histologically. During the study,
      eight (18.2%) animals were lost to follow-up and three (6.8%) were submitted to
      euthanasia. Of the remaining 33 dogs, five (15.2%) presented spontaneous
      regression of the lesions, 26 (78.8%) were cured after treatment, and two (6%)
      continue to be treated. The present cases indicate that many dogs with
      sporotrichosis respond well to treatment and in a few dogs, the disease may be
      self-limiting.

PMID- 16805099
TI  - A case of disseminated mycosis in a German shepherd dog due to Penicillium
      purpurogenum.
AB  - The genus Penicillium is among the most common contaminant fungi in the
      environment. Around 15 species are known to cause opportunistic human mycoses, in
      immunocompromised patients. Until now, Penicillium purpurogenum has been involved
      in only three human cases of pulmonary diseases but no infections in animals have
      been reported. Most disseminated mycoses in dogs are caused by members of the
      genus Aspergillus, with the predisposing factors in these cases being difficult
      to define. The case reported here involved a 4-year-old female German shepherd
      dog (GSD) with forelimb instability and back pain. Clinical examination showed
      hyperthermia, generalized lymphadenomegaly and kyphosis. Radiological findings of
      the spine revealed areas of discospondilitis involving thoracic and lumbar
      vertebrae. Microscopic observations of fine needle aspiration biopsies (FNAB) of
      lymph-nodes showed regular, septate, branching fungal hyphae. Itraconazole
      therapy was started but the subject died six days later. Disseminated necrotic
      areas were detected in enlarged lymph-nodes, liver and spleen. Vertebral
      granulomas within lytic areas in T10-T11 and L2-L3, were observed. Cultures
      inoculated with samples obtained from lymph-node FNAB and bioptic material from
      necropsied organs revealed the presence of pure cultures of Penicillium,
      subsequently identified as P. purpurogenum. Apart from female GSD's suspected
      predisposition to disseminated mycoses described in literature, no other
      predisposing factors were ascertained in this case.

PMID- 16805100
TI  - Biofilm production by clinical isolates of Candida species.
AB  - Candida species are a leading cause of infections especially in immunocompromised
      hosts. Usage of bio-prostheses such as IV lines and urinary catheters provide
      ample opportunity for Candida biofilms to set up a nidus for disease that is not
      easily amenable to conventional antifungal therapy. To understand the prevalence
      of biofilm producers among clinical isolates, 58 Candida isolates from
      immunocompromised patients were examined. Thirty of the 36 (83.3%) blood stream'
      isolates and 18 of the 22 (81.8%) oral isolates were biofilm producers. Biofilm
      producing blood stream isolates were significantly more among non-C. albicans
      Candida (93.1%) in comparison to C. albicans (42.9%).

PMID- 16805101
TI  - Acoustic activation of targeted liquid perfluorocarbon nanoparticles does not
      compromise endothelial integrity.
AB  - Perfluorocarbon nanoparticles consisting essentially of liquid perfluoro-octyl
      bromide (PFOB) core surrounded by a lipid monolayer can serve as highly specific
      site-targeted contrast and therapeutic agents after binding to cellular
      biomarkers. Based on previous findings that ultrasound applied at 2 MHz and 1.9
      mechanical index (MI) for a 5-min duration dramatically enhances the cellular
      interaction of targeted PFOB nanoparticles with melanoma cells in vitro without
      inducing apoptosis or other harmful effects to cells that are targeted, we sought
      to define mechanisms of interaction and the safety profile of ultrasound used in
      conjunction with liquid perfluorocarbon nanoparticles for targeted drug delivery,
      as compared with conventional microbubble ultrasound contrast agents under
      identical insonification conditions. Cell-culture inserts were used to grow a
      confluent monolayer of human umbilical vein endothelial cells. Definity in
      conjunction with continuous wave ultrasound (2.25 MHz for 1 and 5 min) increased
      the permeability of monolayer by four to six times above the normal, decreased
      transendothelial electrical resistance (a sign of reduced membrane integrity),
      and decreased cell viability by approximately 50%. Histological evaluation
      demonstrated extensive disruptions of cell monolayers. Nanoparticles (both
      nontargeted and targeted) elicited no changes in these different measures under
      similar insonification conditions and did not disrupt cell monolayers. We
      hypothesize that ultrasound facilitates drug transport from the perfluorocarbon
      nanoparticles not by cavitation-induced effects on cell membrane but rather by
      direct interaction with the nanoparticles that stimulate lipid exchange and drug
      delivery.

PMID- 16805102
TI  - Effects of cellular fine structure on scattered light pattern.
AB  - Biological cells are complex in both morphological and biochemical structure. The
      effects of cellular fine structure on light scattered from cells are studied by
      employing a three-dimensional code named AETHER which solves the full set of
      Maxwell equations by using the finite-difference time-domain method. It is shown
      that changes in cellular fine structure can cause significant changes in the
      scattered light pattern over particular scattering angles. These changes
      potentially provide the possibility for distinguishability of cellular
      intrastructures. The effects that features of different intrastructure have on
      scattered light are discussed from the viewpoint of diagnosing cellular fine
      structure. Finally, we discuss scattered light patterns for lymphocyte-like cells
      and basophil-like cells.

PMID- 16805103
TI  - LPC cepstral distortion measure for protein sequence comparison.
AB  - Protein sequence comparison is the most powerful tool for the inference of novel
      protein structure and function. This type of inference is commonly based on the
      similar sequence-similar structure-similar function paradigm, and derived by
      sequence similarity searching on databases of protein sequences. As entire
      genomes have been being determined at a rapid rate, computational methods for
      comparing protein sequences will be more essential for probing the complexity of
      molecular machines. In this paper we introduce a pattern-comparison algorithm,
      which is based on the mathematical concepts of linear predictive coding (LPC) and
      LPC cepstral distortion measure, for computing similarities/dissimilarities
      between protein sequences. Experimental results on a real data set of
      functionally related and functionally nonrelated protein sequences have shown the
      effectiveness of the proposed approach on both accuracy and computational
      efficiency.

PMID- 16805104
TI  - Mechanical analysis of chorion softening in prehatching stages of zebrafish
      embryos.
AB  - During early development, the chorion envelope of the zebrafish embryo undergoes
      a thinning process called "chorion softening," which has so far only been
      characterized chemically. In this study, a micromechanical force sensing system
      was used to characterize and quantitate mechanical modifications of the zebrafish
      embryo chorion during early development. Quantitative relationships between
      applied forces and chorion structural deformations were established at various
      embryonic stages. The measured penetration force into the chorion at the blastula
      stage was 1.3-fold greater than those at the prehatching stage. Furthermore,
      chorion elastic modulus values were determined by using a biomembrane elastic
      model. The elastic modulus of the chorion at the blastula stage was 1.66-fold
      greater than that at the prehatching stage, thus indicating that the chorion
      envelope become mechanically "softened" at the prehatching stage. The
      experimental results quantitatively describe "chorion softening," which is most
      likely due to proteolytic activities at the prehatching stage. Gradual chorion
      softening during embryonic development was also artificially achieved by treating
      blastula chorion with pronase, a proteolytic enzyme. The forces required to
      penetrate the pronase-treated chorion were similar to those at the prehatching
      stage. This similarity suggests that "chorion softening" may be induced by the
      release of protease from the embryos, and the chemical nature of the process
      involves proteolytic fragmentation of the ZP2 protein.

PMID- 16805105
TI  - MLEM deconvolution of protein X-ray diffraction images based on a multiple-PSF
      model.
AB  - In this paper we analyze the degradation of protein X-ray diffraction images by
      diffuse light distortion (DLD). In order to correct the degradation, a new
      multiple point spread function (PSF) model is introduced and used to restore X
      ray diffraction image data (XRD). Raw PSFs are collected from isolated spots in
      high-resolution areas on the diffraction patterns which represent the orientation
      of DLDs. An adaptive ridge regression (ARR) technique is used to remove noise
      from the raw PSF data. A target Gaussian function is used to model the raw PSFs.
      A maximum likelihood expectation maximization (MLEM) algorithm combined with a
      multi-PSF model is employed to restore high intensity, asymmetrical protein X-ray
      diffraction data. Experimental results using a single and multiple PSFs are
      presented and discussed. We show that using a multiple PSF model in the
      deconvolution algorithm improved the quality of the XRD and as a result the spot
      integration error (chi-squared) and corresponding electron density mapare
      improved.

PMID- 16805106
TI  - Hybridization-ligation versus parallel overlap assembly: an experimental
      comparison of initial pool generation for direct-proportional length-based DNA
      computing.
AB  - Previously, direct-proportional length-based DNA computing (DPLB-DNAC) for
      solving weighted graph problems has been reported. The proposed DPLB-DNAC has
      been successfully applied to solve the shortest path problem, which is an
      instance of weighted graph problems. The design and development of DPLB-DNAC is
      important in order to extend the capability of DNA computing for solving
      numerical optimization problem. According to DPLB-DNAC, after the initial pool
      generation, the initial solution is subjected to amplification by polymerase
      chain reaction and, finally, the output of the computation is visualized by gel
      electrophoresis. In this paper, however, we give more attention to the initial
      pool generation of DPLB-DNAC. For this purpose, two kinds of initial pool
      generation methods, which are generally used for solving weighted graph problems,
      are evaluated. Those methods are hybridization-ligation and parallel overlap
      assembly (POA). It is found that for DPLB-DNAC, POA is better than that of the
      hybridization-ligation method, in terms of population size, generation time,
      material usage, and efficiency, as supported by the results of actual
      experiments.

PMID- 16805107
TI  - An efficient semi-unsupervised gene selection method via spectral biclustering.
AB  - Gene selection is an important issue in microarray data processing. In this
      paper, we propose an efficient method for selecting relevant genes. First, we use
      spectral biclustering to obtain the best two eigenvectors for class partition.
      Then gene combinations are selected based on the similarity between the genes and
      the best eigenvectors. We demonstrate our semi-unsupervised gene selection method
      using two microarray cancer data sets, i.e., the lymphoma and the liver cancer
      data sets, where our method is able to identify a single gene or a two-gene
      combinations which can lead to predictions with very high accuracy.

PMID- 16805108
TI  - Controlled hidden markov models for dynamically adapting patch clamp experiment
      to estimate Nernst potential of single-ion channels.
AB  - This paper presents novel kernel-based stochastic learning algorithms for
      controlling the kinetics of single-ion channels in a patch clamp experiment. The
      algorithms yield efficient estimates of the equilibrium (Nernst) potential of an
      ion channel. The equilibrium potential of an ion channel is the applied external
      potential difference required to maintain electrochemical equilibrium across the
      ion channel. The algorithm adaptively controls the exploration of the learning
      algorithm to achieve an optimal balance between exploration and exploitation. An
      important feature of the resulting algorithm is that it is guaranteed to minimize
      the experimental effort. We illustrate the efficiency of the algorithms for the
      experimentally determined current voltage curve of a bi-ionic single potassium
      ion channel.

PMID- 16805109
TI  - Adaptive Brownian dynamics simulation for estimating potential mean force in ion
      channel permeation.
AB  - Ion channels are biological nanotubes formed by large protein molecules in the
      cell membrane. This paper presents a novel multiparticle simulation methodology,
      which we call adaptive controlled Brownian dynamics, for estimating the force
      experienced by a permeating ion at each discrete position along the ion
      conducting pathway. The profile of this force, commonly known as the potential of
      mean force, results from the electrostatic interactions between the ions in the
      conduit and all the charges carried by atoms forming the channel the protein, as
      well as the induced charges on the protein wall. The current across the channel
      is solely determined by the potential of mean force encountered by the permeant
      ions. The simulation algorithm yields consistent estimates of this profile. The
      algorithm operates on an angstrom unit spatial scale and femtosecond time scale.
      Numerical simulations on the gramicidin ion channel show that the algorithm
      yields the potential of mean force profile that accurately reproduces
      experimental observations.

PMID- 16805110
TI  - Dielectrophoresis of DNA: time- and frequency-dependent collections on
      microelectrodes.
AB  - This paper reports measurements that characterize the collection of DNA onto
      interdigitated microelectrodes by high-frequency dielectrophoresis. Measurements
      of time-dependent collection of 12 kilobase pair plasmid DNA onto microelectrodes
      by dielectrophoresis show significant reduction in the response as the frequency
      increases from 100 kHz to 20 MHz. Collection time profiles are quantitatively
      measured using fluorescence microscopy over the range 100 kHz to 5 MHz and are
      represented in terms of two parameters: the initial dielectrophoretic collection
      rate, and the initial to steady-state collection transition. Measured values for
      both parameters are consistent with trends in the frequency-dependent real part
      of the effective polarizability measured for the same plasmid DNA using
      dielectric spectroscopy. The experimentally measured parameters are qualitatively
      compared with trends predicted by theory that takes into account
      dielectrophoretic particle movement and diffusion. The differences between
      experiment and theory are discussed with suggested improvements to theoretical
      models, for example, including the effects of electrohydrodynamically driven
      fluid motion.

PMID- 16805111
TI  - Extracellular sensors and extracellular alarmones, which permit cross-talk
      between organisms, determine the levels of alkali tolerance and trigger
      alkaliinduced acid sensitivity in Escherichia coli.
AB  - For several stress responses in Escherichia coli, switching on involves
      conversion by the stress of an extracellular stress sensor (an extracellular
      sensing component, ESC) to an extracellular induction component (EIC), the latter
      functioning as an alarmone and inducing the response. The aim of this study was
      to establish whether alkali tolerance induction at pH 9.0, alkali sensitisation
      induced at pH 5.5 and the acid sensitisation induced at pH 9.0 involve sensing of
      pH changes by ESCs. The techniques involved made use of studies with cell-free
      culture filtrates. With respect to the inducible responses under test, these
      filtrates were prepared either from induced or uninduced cultures and filtrates
      from uninduced cultures were also activated in vitro, by the pH stress, in the
      absence of bacteria. Tests were then made to examine whether EICs (known to be
      needed for all these systems) are formed by activation, at the appropriate pH
      values, of filtrates from pH 7.0-grown cultures (i.e. uninduced culture
      filtrates); appearance of an EIC on activation would indicate the presence in the
      uninduced culture filtrate of an ESC. The studies showed that all three systems
      use ESCs to detect pH changes. Tests involving attempted enzymic and physical
      inactivation of the ESCs, and attempted removal of the ESCs by dialysis, showed
      that the ESC involved in alkali sensitisation is a small very heat-resistant
      protein. Strikingly, protease only partially inactivated the ESCs needed for
      alkali tolerance induction and for acid sensitisation; each system may be
      complex, involving both protein and non-protein (RNA?) ESCs, although other
      explanations are possible. It was also established that appropriate killed
      cultures can induce all three responses when incubated with pH 7.0-grown living
      cultures. The occurrence of ESC/EIC pairs for these three responses has led to
      the evolution of early warning systems for each, the diffusibility of the EICs,
      and their interaction with non-producers, allowing them to act pheromonally,
      inducing sensitive organisms to stress tolerance, prior to exposure to stressor.

PMID- 16805112
TI  - The molecular basis of lactose intolerance.
AB  - A staggering 4000 million people cannot digest lactose, the sugar in milk,
      properly. All mammals, apart from white Northern Europeans and few tribes in
      Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into
      galactose and glucose, after weaning. Lactose intolerance causes gut and a range
      of systemic symptoms, though the threshold to lactose varies considerably between
      ethnic groups and individuals within a group. The molecular basis of inherited
      hypolactasia has yet to be identified, though two polymorphisms in the introns of
      a helicase upstream from the lactase gene correlate closely with hypolactasia,
      and thus lactose intolerance. The symptoms of lactose intolerance are caused by
      gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial
      toxins may play a key role in several other diseases, such as diabetes,
      rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose
      intolerance has been exacerbated because of the addition of products containing
      lactose to various foods and drinks without being on the label. Lactose
      intolerance fits exactly the illness that Charles Darwin suffered from for over
      40 years, and yet was never diagnosed. Darwin missed something else--the key to
      our own evolution--the Rubicon some 300 million years ago that produced lactose
      and lactase in sufficient amounts to be susceptible to natural selection.

PMID- 16805113
TI  - Terms used for the analysis of astigmatism.

PMID- 16805114
TI  - Descemet's stripping with endothelial keratoplasty in 50 eyes: a refractive
      neutral corneal transplant.

PMID- 16805115
TI  - Wavefront-supported photorefractive keratectomy with the Bausch & Lomb Zyoptix in
      patients with myopic astigmatism and suspected keratoconus.
AB  - PURPOSE: To evaluate the safety, efficacy, and visual outcome of wavefront
      supported photorefractive keratectomy (PRK) for the correction of myopia and
      myopic astigmatism in patients with suspected keratoconus. METHODS: Forty eyes of
      20 patients with myopia -4.0 to -8.0 diopters (D) (mean: -6.25 +/- 1.04 D),
      cylinder -1.0 to -2.50 D (mean: -1.61 +/- 0.71 D), and corneal thickness 440 to
      488 microm were treated with wavefront-supported PRK. Corneal topography
      evaluation revealed a significantly irregular cylinder (inferior-superior
      difference > 1.5 D) with possible mild or forme fruste keratoconus. Aberrometry
      was performed with the Hartmann-Shack aberrometer, and corneal data were
      evaluated with the Orbscan system. Eyes were treated with the Technolas 217z
      Bausch & Lomb excimer laser and followed for a minimum of 40 months. RESULTS:
      Following surgery, mean spherical equivalent refraction was +0.33 +/- 0.8 D. It
      was within +/- 0.5 D of the intended refraction in 95% of eyes and within +/- 1.0
      D in 100% of eyes. Mean uncorrected visual acuity improved from 20/400
      preoperatively to 20/25 postoperatively. Mean best spectacle-corrected visual
      acuity (BSCVA) remained unchanged (20/20) or improved to 20/20 in 92.5% of eyes
      and to 20/25 in 7.5% of eyes. Individually, BSCVA did not change in 28 (70%) eyes
      and increased by > or = 2 Snellen lines in 9 (22.5%) eyes; 3 (7.5%) eyes lost 1
      Snellen line because of corneal haze. Laser treatment induced a significant
      flattening of the preoperative inferior corneal steepness in all eyes. Wavefront
      analysis demonstrated a significant decrease in high order aberrations (total
      root-mean-square and coma). CONCLUSIONS: Wavefront-supported PRK appears to be
      effective for the treatment of myopia and astigmatism in patients with suspected
      keratoconus and thin, irregular corneas. Longer follow-up is needed to prove the
      safety of the procedure in this patient population.

PMID- 16805116
TI  - Corneal higher order aberrations: a method to grade keratoconus.
AB  - PURPOSE: To use the anterior corneal surface higher order aberrations as a tool
      to detect and grade keratoconus using corneal map analysis videokeratoscopy.
      METHODS: A prospective observational comparative study of 80 eyes was performed.
      The eyes were divided into two groups. Group A comprised 40 eyes of 20
      asymptomatic individuals with no ocular pathology. Mean sphere was -0.03 diopters
      (D) (range: +0.75 to -0.75 D), mean cylinder was -0.27 D, mean average K was
      43.28 D, and mean uncorrected visual acuity (UCVA) was 1.01. Group B comprised 40
      eyes of 25 patients with keratoconus. Mean sphere was -3.70 D (range: +2.00 to 
      10.00 D), mean cylinder was -3.82 D, mean average K was 49.29, and mean best
      spectacle-corrected visual acuity (BSCVA) was 0.61. RESULTS: In group A, mean
      root-mean-square (RMS) of spherical (Z4 and Z6), coma-like (Z3, Z5, and Z7), and
      higher order aberrations (Z3-7) were 0.38 microm, 0.35 microm, and 0.52 microm,
      respectively. In group B, mean RMS of spherical, coma-like, and higher order
      aberrations were 1.06 microm, 2.90 microm, and 3.14 microm, respectively, for a
      6.0-mm simulated pupil diameter. Mean RMS differences between the two groups were
      0.68 microm (P < or = .0002), 2.55 microm (P < or = .0001), and 2.61 microm (P <
      or = .0001) for spherical, coma-like, and total higher order aberrations,
      respectively. In group B, according to Amsler-Krumeich classification, the mean
      RMS of coma-like aberration was 1.87 microm in grade I (14 eyes), 2.97 microm in
      grade II (11 eyes), 3.46 microm in grade III (12 eyes), and 5.20 microm in grade
      IV (3 eyes). CONCLUSIONS: Corneal higher order aberrations, especially coma-like
      aberrations, are significantly higher in eyes with keratoconus than normal eyes.
      Coma-like aberrations, with the aid of a corneal aberrometry map, are good
      indicators for early detection and grading of keratoconus.

PMID- 16805117
TI  - Comparison of LASIK using the NIDEK EC-5000 optimized aspheric transition zone
      (OATz) and conventional ablation profile.
AB  - PURPOSE: To compare a new ablation algorithm termed the optimized aspheric
      transition zone (OATz) with the conventional laser ablation profile for
      correction of myopic astigmatism. METHODS: LASIK using OATz profile #6 or using
      conventional ablation profile was performed on 98 eyes of 53 patients (OATz #6
      group) and 111 eyes of 66 patients (control #6 group), respectively. Further,
      LASIK using OATz profile #5 or using the conventional ablation profile was
      performed on 109 eyes of 58 patients (OATz #5 group) and 109 eyes of 75 patients
      (control #5 group), respectively. The effective optical zone, uncorrected visual
      acuity, manifest refraction, aberrations, contrast sensitivity, and patient
      satisfaction at 3 months postoperatively were compared between the OATz #6 and
      control #6 groups and between the OATz #5 and control #5 groups. RESULTS: The
      effective optical zones in the OATz #6 group (6.45 +/- 0.29 mm) or OATz #5 group
      (6.40 +/- 0.21 mm) were significantly larger than those in the control #6 group
      (6.33 +/- 0.27 mm) or control #5 group (6.26 +/- 0.25 mm) (P < .01),
      respectively. Uncorrected visual acuity and manifest refraction were similar in
      all groups. The changes in contrast sensitivity were significant and favored the
      OATz #6 (P < .01) and OATz #5 groups (P < .05). The patient satisfaction survey
      found no statistical difference at 3 months postoperatively. CONCLUSIONS:
      Patients treated with the OATz profiles had better visual quality as measured by
      contrast sensitivity and also had larger effective optical zones as compared with
      those treated by the conventional ablation profile.

PMID- 16805118
TI  - Reproducibility of flap thickness with IntraLase FS and Moria LSK-1 and M2
      microkeratomes.
AB  - PURPOSE: To compare flap thickness reproducibility of the femtosecond laser and
      two mechanical microkeratomes. METHODS: Flap thickness for all eyes was measured
      as the difference between the preoperative (day of surgery) full corneal
      thickness and post-flap creation central stromal bed thickness using ultrasonic
      pachymetry. Flap thickness values produced by three different microkeratome
      systems were compared for accuracy and reproducibility. RESULTS: For 99 flaps
      created using the IntraLase FS laser with an intended thickness of 110 microm,
      the mean achieved thickness was 119 +/- 12 microm (range: 82 to 149 microm). In
      100 eyes treated with the Moria LSK-1 microkeratome with an intended flap
      thickness of 160 microm, the mean achieved thickness was 130 +/- 19 microm
      (range: 71 to 186 microm). In 135 eyes treated with the Moria M2 microkeratome
      with an intended flap thickness of 130 microm, mean thickness was 142 +/- 24
      microm (range: 84 to 203 microm). The standard deviation and range of corneal
      flap thickness created with the IntraLase FS laser was significantly smaller than
      either mechanical microkeratome (P < .0001). CONCLUSIONS: When compared to two
      commonly used mechanical microkeratomes, mean achieved flap thickness was more
      reproducible with the IntraLase FS laser, reducing the comparative risk of overly
      thick flaps.

PMID- 16805120
TI  - One-year outcomes of a bilateral randomized prospective clinical trial comparing
      laser subepithelial keratomileusis and photorefractive keratectomy.
AB  - PURPOSE: To compare laser subepithelial keratomileusis (LASEK) and
      photorefractive keratectomy (PRK) in different eyes of the same patients in terms
      of visual acuity, refractive error, and complications over 1 year. METHODS: This
      prospective, randomized, double-masked study comprised 30 active-duty military
      personnel with myopia who underwent LASEK in one eye and PRK in the other eye.
      RESULTS: Twenty-eight patients' results were available for 1-year follow-up. The
      primary outcome measures were visual acuity and refractive error. The mean visual
      acuity for the LASEK group was 1.56 and 1.67 for the PRK group (z = -0.18, P =
      .15). The mean spherical equivalent refraction for the LASEK group was -0.007 D
      and +0.124 D for the PRK group (t = 0.982, P = .40). No significant differences
      were noted in visual acuity or refractive error in the eyes that had LASEK versus
      the eyes that had PRK. CONCLUSIONS: After 1-year follow-up, LASEK and PRK show
      similar levels of visual acuity and refractive error.

PMID- 16805119
TI  - Effect of prophylactic and therapeutic mitomycin C on corneal apoptosis, cellular
      proliferation, haze, and long-term keratocyte density in rabbits.
AB  - PURPOSE: To determine the mechanism through which topical mitomycin C prevents
      and treats corneal haze after photorefractive keratectomy (PRK) and to examine
      the effects of dosage and duration of exposure. METHODS: In 224 New Zealand
      rabbits, -9.0 diopter PRK with mitomycin C or balanced salt solution was
      performed. Haze level was graded at the slit-lamp. Rabbits were sacrificed at 4
      hours, 24 hours, 4 weeks, or 6 months after surgery and immunohistochemistry was
      performed with TUNEL assay, Ki67, and alpha-SMA. RESULTS: TUNEL-positive
      apoptotic cells marginally increased in all mitomycin C groups whereas Ki67
      positive mitotic cells decreased significantly following mitomycin C application.
      A greater decrease in myofibroblasts was noted with prophylactic mitomycin C
      treatment than therapeutic mitomycin C treatment. There was, however, an anterior
      stromal acellular zone (approximately 20% of the total stroma) in eyes treated
      with mitomycin C, which persisted to the maximum follow-up of 6 months.
      CONCLUSIONS: Mitomycin C treatment induces apoptosis of keratocytes and
      myofibroblasts, but the predominate effect in inhibiting or treating haze appears
      to be at the level of blocked replication of keratocytes or other progenitor
      cells of myofibroblasts. Treatment with 0.002% mitomycin C for 12 seconds to 1
      minute appears to be just as effective as higher concentrations for longer
      duration in the rabbit model. However, a persistent decrease in keratocyte
      density in the anterior stroma could be a warning sign for future complications
      and treatment should be reserved for patients with significant risk of developing
      haze after PRK.

PMID- 16805121
TI  - Validation of the Barraquer tonometer for high intraocular pressure estimation.
AB  - PURPOSE: To compare the pneumatonometer and the Tono-Pen XL in a closed ex-vivo
      system in human eye bank eyes at high intraocular pressures (IOP) and evaluate
      the validity of high IOP measurements with the Barraquer tonometer. METHODS:
      Intraocular pressure was monitored by cannulation of the anterior chamber and
      vitreous cavity in eight human cadaver eyes (mean donor age: 77.3 +/- 4.9 years,
      range: 72 to 84 years). Intraocular pressure measurements were taken at 50, 65,
      and 90 mmHg with the Tono-Pen XL and pneumatonometer. Intraocular pressure was
      raised to 110 mmHg and then the eyes were deflated slowly until they reached 50
      mmHg. Pressure readings with the Barraquer tonometer were recorded when the
      corneal tonometer interface reached the inner and outer rings. RESULTS: The Tono
      Pen XL underestimated IOP, a tendency that was more evident at higher IOP In
      contrast, the pneumatonometer was more accurate and reliable at IOP of 50 and 65
      mmHg but its readings underestimated IOP at 90 mmHg. The Barraquer tonometer used
      in this experiment accurately estimated high IOP A variability of 5.9 mmHg and
      5.8 mmHg were recorded for the inner and outer ring, respectively. CONCLUSIONS:
      The Tono-pen XL is an inadequate instrument to assess pressures normally
      encountered during LASIK flap creation in an ex vivo model using human cadaver
      eyes. The pneumatonometer and the Barraquer tonometer are accurate instruments at
      high IOP; however, the pneumatonometer underestimated pressures around 90 mmHg.

PMID- 16805122
TI  - The effect of topical apraclonidine on subconjunctival hemorrhage and flap
      adherence in LASIK patients.
AB  - PURPOSE: To determine whether the use of topical apraclonidine just before the
      LASIK procedure prevents subconjunctival hemorrhage and to study its effect on
      postoperative flap adherence. METHODS: Topical apraclonidine 0.125% was randomly
      applied to 1 eye of 66 myopic patients who underwent primary bilateral LASIK.
      Apraclonidine was instilled 1 hour prior to and 30 seconds before placing the
      vacuum ring of the microkeratome, whereas the other eye served as control. Thirty
      minutes after the operation, all patients were examined by the surgeon to
      evaluate hyperemia and identify flap-related complications (eg, slippage,
      dislocation, or flap folds). The size of subconjunctival hemorrhage was also
      evaluated on postoperative days 1 and 7. All 132 eyes in the study were examined
      after surgery to identify flap folds and/or their dislocation. RESULTS: In the
      apraclonidine group, 48 (72.8%) eyes had no hyperemia, 16 (24.2%) eyes had mild
      hyperemia, 2 (3%) eyes had moderate hyperemia, and no (0%) eyes had severe
      hyperemia. In the control group, 37 (56.1%) eyes had mild hyperemia, 21 (31.8%)
      eyes had moderate hyperemia, 1 (1.5%) eye had severe hyperemia, and 7 (10.6%)
      eyes had no hyperemia. In the apraclonidine group, 44 (66.7%) eyes had no
      subconjunctival hemorrhage (grade 0); grade 1 was present in 19 (28.8%) eyes
      whereas grades 2 and 3 were present in 2 (3%) eyes and 1 (1.5%) eye,
      respectively. In the control group, 19 (28.8%) eyes showed grade 0, 13 (19.7%)
      eyes had grade 1, and grades 2 and 3 were present in 20 (30.3%) eyes and 14
      (21.2%) eyes, respectively. Chi-square test showed a highly significant
      difference between the two groups (P < .001). No flap-related problems were
      reported in either group. CONCLUSIONS: Topical apraclonidine applied before LASIK
      surgery may prevent immediate postoperative hyperemia and prolonged
      subconjunctival hemorrhage by its alpha-mimetic vasoconstrictor effect without
      inducing flap adherence complication.

PMID- 16805123
TI  - One-year outcomes of epi-LASIK for myopia.
AB  - PURPOSE: To evaluate the early clinical outcomes of epi-LASIK for myopia.
      METHODS: This study comprised 302 eyes of 162 patients. Epi-LASIK was performed
      with an automatically rotational epikeratome (KM-5000D). Epithelial separation
      was achieved mechanically without the use of alcohol. After laser ablation, the
      epithelial sheet was repositioned and a therapeutic contact lens was applied to
      the cornea immediately for 3 to 5 days. Postoperative visual acuity, symptoms,
      epithelial sheet, contrast sensitivity, wavefront aberration, and haze formation
      were evaluated 3, 6, and 12 months postoperatively. RESULTS: Of the 302 eyes, 72
      eyes (42 patients) with a mean spherical equivalent refraction of -9.13 +/- 4.23
      diopters (D) (range: -1.25 to -19.0 D) had > 1-year follow-up. One eye failed to
      make the epithelial sheet because of the narrow palpebral fissure. An integrated
      epithelial sheet with a diameter of 8 to 9 mm was made in 289 (95.7%) eyes,
      leaving a superior hinge of approximately 2 to 4 mm. In 1 eye, stromal tissue
      remained in the epithelial sheet. Free epithelial flaps were made in 12 (4%)
      eyes. Mild discomfort was reported by 150 patients (282 eyes, 93.4%). Twelve
      patients (20 eyes, 6.6%) reported moderate symptoms. At 1 day postoperatively,
      corneal epithelium was almost transparent or had mild focal edema in 288 (95.4%)
      eyes; moderate edema was reported in 14 (4.6%) eyes. At 1 year postoperatively,
      spherical equivalent refraction of 60 (83.3%) eyes was within +/- 1.0 D of
      attempted refraction. Grade 0.5 haze was found in 2 eyes; all other eyes had no
      haze. No eye lost any lines of best spectacle-corrected visual acuity (BSCVA),
      whereas 12 (16.7%) of 72 eyes gained one or two lines of BSCVA. Contrast
      sensitivity decreased 1 month postoperatively and was restored to preoperative
      levels in eyes with preoperative spherical equivalent refraction < -10.0 D.
      Higher order aberration increased significantly postoperatively. CONCLUSIONS: Epi
      LASIK is a safe and efficient method to correct myopia with the advantage that it
      has only mild symptoms and mild haze. A larger study with longer follow-up is
      needed to determine its long-term clinical outcomes.

PMID- 16805124
TI  - Hyperopic LASIK retreatments with the Technolas laser.
AB  - PURPOSE: To evaluate the safety, efficacy, and predictability of hyperopic LASIK
      retreatments. METHODS: This retrospective, consecutive, non-comparative,
      observational study included 85 eyes that underwent hyperopic LASIK retreatment
      with 1-year follow-up. Complete ophthalmic examination included distance
      uncorrected (UCVA) and best spectacle-corrected visual acuity (BSCVA),
      cycloplegic refraction, and pachymetry. Patients were divided into two groups
      according to the preoperative spherical equivalent refraction: group 1, < or =
      +3.9 diopters (D) and group 2, > or = +4.0 D. RESULTS: The UCVA improved from
      0.31 +/- 0.2 to 0.7 +/- 0.2 in group 1 and from 0.2 +/- 0.2 to 0.6 +/- 0.2 in
      group 2 following retreatment. Mean spherical equivalent refraction improved from
      +2.8 +/- 0.85 to +0.2 +/- 0.9 in group 1 and from +5.3 +/- 0.9 to +0.3 +/- 1.3 in
      group 2 after retreatment. In group 1, 32 (72.7%) of 44 eyes had BSCVA > or =
      20/25, and in group 2, 24 (58.5%) of 41 eyes had BSCVA > or = 20/25. After
      primary hyperopic LASIK, 25 (56.8%) of 44 eyes in group 1 and 19 (46.3%) of 41
      eyes in group 2 maintained BSCVA or gained > or = 1 lines postoperatively in
      contrast to 21 (47.7%) of 44 eyes in group 1 and 22 (53.9%) of 41 eyes in group 2
      after retreatment. In group 1, 11 (25%) of 44 eyes lost > or = 2 lines of BSCVA
      after initial hyperopic LASIK compared to 14 (31.8%) of 44 eyes after
      retreatment. In group 2, 10 (24.4%) of 41 eyes lost > or = 2 lines of BSCVA after
      initial hyperopic LASIK compared to 12 (29.2%) of 41 eyes after retreatment.
      After hyperopic LASIK retreatment, 31 (70.5%) of 44 eyes in group 1 and 19
      (46.4%) of 41 eyes in group 2 were within +/- 0.5 D of emmetropia. Safety was 0.9
      in both groups and efficacy was 0.8 and 0.7 in groups 1 and 2, respectively.
      Complications included epithelial ingrowth of 1 to 3 mm (30%) and flap edge
      melting (2%). CONCLUSIONS: Hyperopic LASIK retreatment improved the refractive
      results of initial hyperopic LASIK surgery with 20% to 30% of eyes gaining > or =
      1 lines of BSCVA. The loss of BSCVA was greater after primary hyperopic LASIK
      than after retreatment.

PMID- 16805125
TI  - Corneal light backscatter measured by optical coherence tomography after LASIK.
AB  - PURPOSE: To objectively quantify corneal light backscatter after LASIK using
      optical coherence tomography (OCT). METHODS: Twenty-eight eyes of 14 patients
      (mean age: 39.9 +/- 8.6 years) underwent LASIK surgery. Corneal images were taken
      with a custom built anterior segment OCT at 1310 nm before and 1 day, 1 week, and
      1 month after surgery. Backscattered light from the epithelium and 10 equally
      divided corneal stromal layers of the central cornea were analyzed using custom
      software. Light scattering of the interface area (defined as seven image pixels
      [46.2 microm] in depth centered by the peak corresponding to the interface
      between the corneal flap and bed) was also calculated and compared to the light
      backscatter at an equivalent depth of the respective preoperative cornea.
      RESULTS: There were significant differences of light backscatter in different
      layers (analysis of variance [ANOVA]: F(10, 130) = 44.89, P = .0001), but no
      significant differences between right and left eyes preoperatively (ANOVA: F(10,
      130) = 1.16, P = .32). After surgery, there were significant differences in light
      backscatter profiles of the central cornea (repeated measures ANOVA: F(30, 810) =
      7.70, P = .0001) with significant increases at approximately 140 to 190 microm in
      depth from the corneal front surface at 1 day (post hoc test: P = .004) and 1
      week (post hoc test: P = .001) postoperatively, compared to the baseline. One
      month after surgery, light backscatter increased significantly in the epithelium
      (post hoc test: P = .0001) and decreased significantly (post hoc test: P = .0001)
      at approximately 100 to 140 microm in depth. Light backscatter results of these
      interface areas (repeated measures ANOVA: F(3, 81) = 21.29, P = .0001) showed
      significant increases at 1 day and 1 week postoperatively (post hoc tests: P =
      .0001) compared to baseline results and 1-month postoperative results.
      CONCLUSIONS: Objective and quantitative analysis of corneal light backscatter
      from OCT demonstrated increasing comeal light scattering at the interface and
      subsequent recovery.

PMID- 16805126
TI  - One-year clinical results of photorefractive keratectomy with a solid-state laser
      for refractive surgery.
AB  - PURPOSE: To investigate the safety, efficacy, and stability of photorefractive
      keratectomy (PRK) performed with a newly developed solid-state laser after 1-year
      follow-up. METHODS: The all-solid-state, Q-switched, frequency-shifted laser
      (LaserSoft; Katana Technologies, Berlin, Germany) with a Gaussian spot diameter
      of 0.2 mm and repetition rate of 1 kHz was used. Eleven eyes of six patients were
      treated with PRK. The mean outcome measures were uncorrected visual acuity
      (UCVA), best spectacle-corrected visual acuity (BSCVA), corneal topography, and
      corneal transparency. All patients were evaluated at 1, 3, 6, and 12 months
      postoperatively. RESULTS: At 12-month follow-up no eye lost lines of BSCVA and
      UCVA improved in all eyes. All eyes were within +/- 1.00 diopters (D) and 8 (73%)
      eyes were within +/- 0.50 D of emmetropia. CONCLUSIONS: Clinical results at 1
      year were promising, with good safety, efficacy, and stability of the visual and
      refractive outcome.

PMID- 16805127
TI  - Epi-LASIK after amputation of a LASIK flap.
AB  - PURPOSE: To demonstrate the feasibility of performing epi-LASIK after amputation
      of a LASIK flap. METHODS: Three months following complicated primary LASIK and
      immediate flap amputation, a Lasitome microkeratome (Gebauer, Neuhausen,
      Germany), equipped with an epi-head and -blade, was used to perform an epi-LASIK
      surface ablation. RESULTS: Despite uneven stromal contour at the site of the
      original hinge after amputation of the LASIK flap, the microkeratome passage was
      uneventful, resulting in a regular epithelial flap. Laser ablation was performed
      and the epithelial flap was repositioned. CONCLUSIONS: Epi-LASIK was completed
      with no intraoperative complication in the presence of an irregular stromal
      surface after amputation of a LASIK flap. This procedure may extend our options
      in the management of LASIK flap-related complications.

PMID- 16805128
TI  - Acanthamoeba keratitis after LASIK.
AB  - PURPOSE: To report a case of Acanthamoeba infection following LASIK. METHODS: A
      20-year-old woman developed pain, redness, decreased vision, and corneal
      infiltrate in the right eye 15 days after bilateral LASIK. She did not use
      contact lenses postoperatively. Patient examination 3 months after surgery
      revealed a large, central, full-thickness corneal infiltrate with multiple
      satellite lesions in the right eye. Corneal scrapings were taken and the flap
      excised, and submitted for histopathologic examination. RESULTS: Microscopic
      examination of smears revealed Acanthamoeba cysts and non-nutrient agar showed a
      significant growth of Acanthamoeba. Histopathology examination of the excised
      flap demonstrated numerous Acanthamoeba cysts in tissue sections. The infiltrate
      was treated with a combination of topical polyhexamethylene biguanide,
      chlorhexidine, atropine sulfate, and oral itraconazole and resolved within 2
      months. CONCLUSIONS: Laser in situ keratomileusis can be complicated by
      Acanthamoeba infection. Microbiologic evaluation is essential for accurate early
      diagnosis and treatment.

PMID- 16805129
TI  - Fourier analysis of single running suture adjustment in penetrating and deep
      lamellar keratoplasty.
AB  - PURPOSE: To prospectively evaluate clinical and visual results of running suture
      adjustment after keratoplasty. METHODS: Thirty-seven eyes of 33 patients received
      running suture adjustment after keratoplasty. Changes in uncorrected visual
      acuity, distance best spectacle-corrected visual acuity (BSCVA), refraction, and
      Fourier analysis constituents were assessed before and after suture adjustment.
      RESULTS: Thirty eyes, which had improvement of distance BSCVA soon after suture
      adjustment, maintained improvement at 1 year, whereas 7 eyes with decreased
      distance BSCVA soon after suture adjustment experienced no improvement at 1 year.
      Patients with poor distance BSCVA at 1 year had significantly higher high order
      irregularity than patients with better distance BSCVA despite similar cylindrical
      power outcomes.

PMID- 16805130
TI  - Contribution of stem cells to skeletal muscle regeneration.
AB  - Stem cells for skeletal muscle originate from dermomyotome of the embryo. The
      early marker of these cells is expression of both transcription factors Pax3 and
      Pax7 (Pax3+/Pax7+ cells). The skeletal muscles in the adult organism have a
      remarkable ability to regenerate. Skeletal muscle damage induces degenerative
      phase, followed by activation of inflammatory and satellite cells. The satellite
      cells are quiescent myogenic precursor cells located between the basal membrane
      and the sarcolemma of myofiber and they are characterized by Pax7 expression.
      Activation of the satellite cells is regulated by muscle growth and chemokines.
      Apart from the satellite cells, a population of adult stem cells (muscle side
      population--mSP) exists in the skeletal muscles. Moreover, the cells trafficking
      from different tissues may be involved in the regeneration of damaged muscle.
      Trafficking of cells in the process of damaged muscle regeneration may be traced
      in the SCID mice.

PMID- 16805131
TI  - Loss and recovery of androgen receptor protein expression in the adult rat testis
      following androgen withdrawal by ethane dimethanesulfonate.
AB  - Androgens are especially important for the maintenance of spermatogenesis in
      adulthood and the experimental withdrawal of testosterone (T) production by
      ethane dimenthanesulfonate (EDS) is a valuable tool for studying androgen
      dependent events of spermatogenesis. The aim of the present study was to
      investigate the specific changes in immunoexpression of androgen receptor (AR) in
      the testis in relation to degeneration and regeneration of Leydig cell (LC)
      population and seminiferous epithelium. Immunohistochemistry for AR and 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) as well as TUNEL assay for apoptosis
      were performed on testicular sections of control and EDS-treated rats. Serum LH
      and T levels were measured by RIA. Our results revealed a total loss of AR
      immunoexpression from the nuclei of Sertoli (SCs), LCs and peritubular cells
      during the first week after EDS administration and that coincided with severe
      drop in T levels. Two weeks after EDS administration, the AR expression was
      recovered in these cells but normal stage-specificity in SCs was replaced by
      uniform intensity of AR immunostaining at all the stages of the spermatogenic
      cycle. The stage-specific pattern of androgen expression in SCs with a maximum at
      stages VII-VIII appeared 5 weeks after treatment. LC immunoreactivity for 3beta
      HSD at different time points after EDS administration correlated with values of T
      concentration. The maximal germ cell apoptosis on day 7 was followed by total
      loss of elongated spermatids 2 weeks after EDS treatment. Regeneration of
      seminiferous epithelium 3 weeks after EDS administration and onwards occurred in
      tandem with the development of new LC population indicated by the appearance of
      3beta-HSD-positive cells and gradual increase in T production. The specific
      changes in AR after EDS including their loss and recovery in Sertoli cells
      paralleled with degenerative and regenerative events in Leydig and germ cell
      populations, confirming close functional relationship between Sertoli, Leydig and
      germ cells.

PMID- 16805132
TI  - Multiple dexamethasone treatment affects morphometric parameters of gonadotrophic
      cells in adult female rats.
AB  - Exposure to glucocorticoids leads to numerous changes in various biological
      systems including the reproductive system. The aim of the present work was to
      find out whether dexamethasone (Dx) treatment of adult female rats would
      influence the histological and morphometric characteristics of the pituitary
      gonadotrophic cells (luteinizing--LH cells and follicle stimulating--FSH cells).
      One group of female Wistar rats received Dx injections on three consecutive days
      in doses 1.0, 0.5 and 0.5 mg/kg b.w. respectively, while the control rats were
      treated with equivalent volumes of saline. Experimental and control animals were
      sacrificed 24 h and 72 h after the last injection. The peroxidase-antiperoxidase
      (PAP) immunocytochemical procedure was used to study the LH and FSH cells. The
      stereological and morphometric analyses showed that multiple Dx treatments of
      female rats significantly decreased the volume of LH cells and the volume of
      their nuclei 24 h and 72 h after the last Dx injection in comparison with control
      values. At 24 h after Dx treatment, the volume density of LH cells was
      significantly increased, but at 72 h differences between the experimental and
      control groups were insignificant. The increase in number of LH cells per unit
      area (mm2) was significant at both timepoints (24 h and 72 h). Stereologic and
      morphometric characteristics of FSH cells was changed after Dx treatment in the
      same manner as that of LH cells, except for the volume density, where a
      significant increase was established 24 h and 72 h after the last Dx application.
      These results clearly demonstrate that 24 h and 72 h after the last of three Dx
      injections there were changes in the immunocytochemical and morphometric features
      of gonadotrophic cells.

PMID- 16805133
TI  - NK cell depletion and recovery in SCID mice treated with anti-NK1.1 antibody.
AB  - The anti-NK1.1 antibody produced by PK136 hybridoma cell line administered
      subcutaneously to SCID mice effectively decreased the level of peripheral blood
      NK cells and weight of the spleen for 3-4 days. The antibody treatment did not
      harm the general state of the animal, and may be practically applied in xenograft
      experiments.

PMID- 16805134
TI  - Mobilization of human hematopoietic stem/progenitor-enriched CD34+ cells into
      peripheral blood during stress related to ischemic stroke.
AB  - The bone marrow-derived stem/progenitor cells were demonstrated to play an
      important role in a regeneration of damaged tissue. Based on these observations
      we asked whether the stroke-related stress triggers mobilization of
      stem/progenitor cells from the bone marrow into the peripheral blood, which
      subsequently could contribute to regeneration of damaged organs. To address this
      issue, the peripheral blood samples were harvested from patients with ischemic
      stroke during the first 24 hrs as well as after the 48 (2nd day) and 144 hrs (6th
      day) since the manifestation of symptoms. In these patients we evaluated the
      percentage of hematopoietic stem/progenitor-enriched CD34+ cells by employing
      flow cytometry and the number of hematopoietic progenitor cells for the
      granulocyto-monocytic (CFU-GM) and erythroid (BFU-E)-lineages circulating in
      peripheral blood. We concluded that stress related to ischemic stroke triggers
      the mobilization of hematopoietic stem/progenitor cells from the bone marrow into
      peripheral blood. These circulating stem/progenitor cells may play an important
      role in the process of regeneration of the ischemic tissue.

PMID- 16805135
TI  - Interleukin-2 (IL-2) expression in livers of patients with chronic hepatitis C
      virus (HCV) infection.
AB  - The studies performed till now have pointed to an increased serum levels of
      interleukin 2 (IL-2) in infection with hepatitis C virus (HCV). The present study
      was aimed at examining intrahepatic expression of IL-2 in children (n=15) and in
      adults (n=11) with chronic hepatitis C as well as its correlations with
      histological lesions and selected clinical data. The immunocytochemical
      techniques and in situ hybridization method were applied at light and electron
      microscopy level. Under the light microscope, expression of IL-2 was analysed
      semiquantitatively. As compared to the control material, in livers of both groups
      of chronic hepatitis C patients augmented expression of IL-2 was demonstrated.
      The reaction product was localized mainly in the cytoplasm of hepatocytes which
      was confirmed by hybridocytochemistry. The mean proportion of cells with positive
      reaction for IL-2 mRNA was significantly lower than the proportion of cells
      positive for the respective protein. No correlation was disclosed between IL-2
      expression on one hand and grading or staging, alanine aminotransferase (ALT) and
      HCV RNA levels in serum on the other. At the ultrastructural level, IL-2 in
      hepatocytes was present mainly in the endoplasmic reticulum and mitochondria. Our
      studies have confirmed augmented expression of IL-2 in livers of patients with
      chronic hepatitis C and have demonstrated that hepatocytes represent the
      principal source of the cytokine in HCV in vivo infection. Moreover, expression
      of IL-2 in the infection was examined for the first time at the ultrastructural
      level. Mitochondrial localization of IL-2 suggests a direct involvement of the
      cytokine in disturbed function of the organelles.

PMID- 16805136
TI  - Stromal myofibroblasts in breast cancer: relations between their occurrence,
      tumor grade and expression of some tumour markers.
AB  - It is suggested that tumour stromal myofibroblasts exert an unfavourable effect
      on the biology of breast cancer. We are aware of only a single study which
      examined relationships between manifestation of myofibroblasts in the stroma of
      breast cancer and clinicopathological data of the patients. The present study was
      aimed at estimation of the effect exerted by myofibroblasts present in the tumour
      stroma on principal pathological parameters and on expression of Ki67, P53 and
      HER-2 proteins in the group of the most frequent breast cancers, the ductal
      cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in
      G2 and 20 in G3), immunohistochemical reactions were performed to detect
      expression of smooth muscle actin (SMA) in order to visualize myofibroblasts,
      Ki67, P53 and HER-2. The studies demonstrated that the most numerous
      myofibroblasts were present in G3 cases and they were the least frequent in G1
      cases (P = 0.02). Positive correlations were observed between the presence of
      myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer
      cells in the entire group (P < 0.001 and P = 0.001, respectively), in G2 cases (P
      = 0.003 and P = 0.03) and in G3 cases (P = 0.01 and P = 0.03). Considering that
      the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic
      factors, the elevated content of myofibroblasts in tumour stroma is probably
      typical for cases with worse prognosis.

PMID- 16805137
TI  - Evaluation of sperm genomic integrity of normozoospermic men: a prospective
      study.
AB  - The objective of our study was to evaluate the incidence of spermatozoa with
      nuclear DNA strand breaks in patients with normal routine sperm parameters (26
      subjects). Sperm DNA fragmentation was measured using TUNEL test assessed in flow
      cytometer. Variable percentages of sperm with damaged DNA (9.42 +/- 7.68%; range:
      2-36) were found. Two categories of patients were distinguished: (1) patients (8
      out of 26 subjects) with < or = 4% of TUNEL-positive sperm and (2) patients (18
      out of 26 subjects) with > 4% of TUNEL-positive sperm. A significantly lower
      percentage of normal sperm forms was found in patients with > 4% of TUNEL
      positive sperm than in patients with < or = 4% of TUNEL-positive sperm. Moreover,
      a significant negative correlation (r(s) = -0.50) was noted only between a
      proportion of normal sperm forms and a proportion of TUNEL-positive spermatozoa.
      In electron microscope, a large number of spermatozoa with immature chromatin was
      observed more frequently in subjects with > 4% of TUNEL-positive cells (11 out of
      18 subjects). Our results suggest that in some patients with normal routine sperm
      parameters, DNA fragmentation may be associated with poor sperm morphology. The
      diminished sperm genomic integrity may result from molecular disturbances in
      nuclear remodeling process during spermiogenesis. TUNEL assay is a screening tool
      that may help to discriminate between fertile and infertile men and may help to
      predict successful in vitro fertilization.

PMID- 16805138
TI  - Localization of the DAZ gene expression in seminiferous tubules of patients with
      spermatogenic disorders.
AB  - The research on the expression and mutations of DAZ and its homologues in human
      and other mammals suggests that protein products of these genes can mainly affect
      development of germinal cells. The aim of the present study was to analyze the
      expression of the DAZ gene in seminiferous tubules of six men with spermatogenic
      disorders (hypospermatogenesis and spermatogenic arrest). The results based on
      the RT-PCR IS technique demonstrated that the DAZ product was present only in
      some seminiferous tubules and the fluorescence intensity was different within
      individual tubules. The most intense fluorescence characterised the
      spermatogonia, especially these organised in small groups inside separate
      tubules. In the patients with spermatogenic arrest at the spermatocyte stage, the
      DAZ gene transcripts were also found in primary spermatocytes. However, the
      fluorescence intensity of primary spermatocytes, except the fluorescence of the
      spermatocytes localised upon the lumen, was weaker than the fluorescence of
      spermatogonia. The results of our study showed that DAZ gene activity seems to
      correspond to the proliferative activity of stem cells of germinal epithelium.

PMID- 16805139
TI  - DNA damage induced by mutagens in plant and human cell nuclei in acellular comet
      assay.
AB  - Higher plant cells have a long tradition of use in the studies on environmental
      mutagenesis in situ, especially in relation to human health risk determination.
      The studies on the response of plant and human cells to physical and chemical
      mutagens showed differences in their sensitivity. The differences in the presence
      of cell components in plants and humans could influence such response.
      Additionally, the level of the organization of the employed material could
      influence DNA-damaging effect: leukocytes are isolated cells and plant--an intact
      organism. To preclude these obstacles, the effects of direct treatment of
      isolated nuclei with genotoxic agents were determined to compare the sensitivity
      of plant and human cells. In the present study, we have determined the DNA
      damaging effects of two chemical mutagens: maleic acid hydrazide (MH) and N
      methyl-N-nitroso-urea (MNU) applied to isolated nuclei of both plant and human
      cells. In order to compare the sensitivity of the nuclei of Nicotiana tabacum
      var. xanthi and the nuclei of leukocytes, the acellular Comet assay was carried
      out. The results showed higher sensitivity of the nuclei of leukocytes as
      compared to the nuclei of plant cells to mutagenic treatment with the applied
      doses of MH and MNU.

PMID- 16805140
TI  - Microtubules with different diameter, protofilament number and protofilament
      spacing in Ornithogalum umbellatum ovary epidermis cells.
AB  - Microtubules present in the epidermis of Ornithogalum umbellatum ovary in the
      area of lipotubuloids (i.e. aggregates of lipid bodies surrounded by
      microtubules) are 25-51 nm in diameter. They consist mainly of 10 and 11,
      sometimes 9 and 12 protofilaments. An average diameter of microtubule consisting
      of 9 subunits is about 32 nm, of 10-35 nm, of 11-38 nm and of 12-43 nm, however,
      individual microtubules in each category significantly vary in size. These
      differences result from varying distance between protofilaments in microtubule
      walls and diameters of protofilaments: in thin microtubules they are densely
      packed and smaller while in thicker ones they are loosely arranged and bigger. A
      hypothesis has been put forward that changes in microtubule diameter depend on
      structural changes associated with their functional status and are executed by
      modifications of protofilament arrangement density and their diameters in
      microtubule wall. The above hypothesis seems to be in agreement with the opinion
      formed on the basis of in vitro image of microtubules, that lateral contact
      between tubulin subunits in neighboring protofilaments indicates some flexibility
      and changeability during microtubule function.

PMID- 16805141
TI  - SCAT in the wilderness.

PMID- 16805142
TI  - Investigating carbon monoxide exposure on Denali.
AB  - OBJECTIVE: This exploratory study assessed a potential relationship between
      elevated carboxyhemoglobin (COHb) levels and acute mountain sickness (AMS) at
      4300 m on Denali. Additional analysis assessed the relationship among COHb
      levels, AMS, and climber characteristics and behaviors. METHODS: Participants
      were screened for AMS with the Lake Louise Self-Report questionnaire and answered
      questions focusing on AMS symptoms, prevention, and previous altitude illness.
      Levels of COHb were measured by serum cooximetry. Additional questions assessed
      stove practices, climbing practices, and climber behaviors. Nonparametric
      statistical analyses were performed to examine potential relationships among COHb
      levels, AMS symptoms, and climber behaviors. RESULTS: A total of 146 climbers
      participated in the study. Eighteen climbers (12.5%) were positive for carbon
      monoxide (CO) exposure and 20 (13.7%) met criteria for AMS. No significant
      relationship was observed between positive CO exposure and positive criteria for
      AMS. Climbers descending the mountain were 3.6 times more likely to meet the
      study criteria for positive CO exposure compared with those ascending the
      mountain (P = .42). In addition, COHb levels were significantly higher for those
      descending the mountain (P = .012) and for those taking prophylactic medications
      (P = .010). Climbers meeting positive criteria for AMS operated their stoves
      significantly longer (P = .047). CONCLUSIONS: No significant relationship between
      AMS symptoms and CO exposure was observed. This may have been affected by the low
      percentage of climbers reporting AMS symptoms, as well as limited power.
      Descending climbers had a 3.6 times increased risk of CO exposure compared with
      ascending climbers and had significantly higher COHb scores. Increased hours of
      stove operation was significantly linked to climbers who also met criteria for
      AMS.

PMID- 16805143
TI  - Improvised cricothyrotomy provides reliable airway access in an unembalmed human
      cadaver model.
AB  - OBJECTIVE: Patients with injuries requiring surgical airway management occurring
      far from medical care might benefit from the availability of a simple, reliable,
      improvisational method of cricothyrotomy with materials available in a wilderness
      or prehospital setting. We evaluated an improvised cricothyrotomy device in an
      experimental, unembalmed human cadaver model. METHODS: A high-flow intravenous
      spike and drip chamber was cut through the drip chamber and used as the sole
      apparatus for performing cricothyrotomy on unembalmed cadavers whose anterior
      neck surfaces and deep tissues were warmed to or near body temperature. Correct
      placement in the trachea and damage to the posterior wall of the trachea were
      assessed by either fiberoptic bronchoscopy or neck dissection. Video recordings
      were used to time each procedure. Each operator was responsible for both device
      insertion and bag valve mask attachment and ventilation, modeling as the sole
      care provider for the patient. RESULTS: One physician and 3 emergency medicine
      residents, all without previous, specific instruction, performed 10 procedures on
      5 female and 5 male unembalmed cadavers weighing a mean of 65 kg (range 45-110
      kg). All 10 attempts at placement of the intravenous tubing spike through the
      cricothyroid membrane were successful. On 2 attempts, the initial placement of
      the device was incorrect, but the error was immediately identified on attempt to
      ventilate the patient. Repositioning of the device resulted in appropriate
      cannulation of the trachea in both attempts. The median time span from manual
      identification of the cricothyroid membrane to percutaneous access and connection
      of the bag valve mask with successful ventilation was 27.3 seconds. Violation of
      the posterior tracheal wall was not seen on any of the 5 procedures in which
      fiberoptic visualization was available or in the 5 procedures evaluated by neck
      dissection. CONCLUSIONS: Cricothyrotomy is the quickest and most effective method
      for obtaining airway access when nonsurgical methods of securing the airway are
      contraindicated or fail. Although frequently described, no improvised airway
      devices of this type have been tested in a systematic manner. We tested the
      reliability and utility of cricothyrotomy with a high-flow intravenous spike and
      drip chamber. Our results suggest that the spike and drip chamber is a plausible
      means of temporarily establishing airway access in patients with acute airway
      obstruction in a wilderness or prehospital environment.

PMID- 16805144
TI  - Prevention of acute mountain sickness by acetazolamide in Nepali porters: a
      double-blind controlled trial.
AB  - OBJECTIVE: This study aimed to determine the efficacy, tolerability, and
      practicality of acetazolamide for the prevention of acute mountain sickness (AMS)
      in Nepali trekking porters early in the trekking season. METHODS: This study was
      a randomized, double-blind controlled trial with 400 male Nepali porters in the
      Mount Everest region of Nepal, trekking from Namche Bazaar (3440 m) to Lobuche
      (4930 m), the study endpoint. Participants were randomized to receive 250 mg
      acetazolamide daily or placebo, and AMS symptom scores (Lake Louise) were
      compared in highlanders vs lowlanders. RESULTS: Only 109 (27.2%) of the 400
      porters completed the trial (28 highlanders, 81 lowlanders). The rest either
      dropped out (275/400 porters, 68.8%) or were excluded (16/400 porters, 4%). Acute
      mountain sickness occurred in 13 (11.9%) of 109 porters; all were lowlanders; 7
      were taking acetazolamide, 6 taking placebo. Birthplace, acclimatization in the
      week before the trial, ascent rate, and rest days were the most important
      variables affecting the incidence of AMS. No highlanders, but 13 (16.1%) of 81
      lowlanders had AMS (P = .016). Acclimatization in the pretrial week reduced AMS
      incidence (P = .013), as did a slower ascent rate (P = .0126), but rest days were
      the most potent prophylactic variable (P = .0001). Side effects were more
      frequent in porters taking acetazolamide than in the placebo group (P = .0001),
      but there were no serious side effects. CONCLUSIONS: Acetazolamide was tolerable,
      but impractical for the routine prevention of AMS in Nepali porters. A good
      trekking schedule and adequate acclimatization remain the most effective
      preventive measures. This study identified lowland porters as a high-risk group
      for developing AMS.

PMID- 16805145
TI  - Laboratory evaluation of the 3-bowl system used for washing-up eating utensils in
      the field.
AB  - OBJECTIVE: A 3-bowl system is used for washing-up eating utensils on many
      expeditions when running water is not available. The utensils are washed in the
      first bowl until they are visibly clean, rinsed in the second bowl, and
      disinfected in the third bowl. The objective of this study was to evaluate the
      efficacy of this system in reducing bacterial loads on contaminated utensils and
      to compare it with alternative washing-up methods. METHODS: Different washing-up
      systems were tested with a simulated dish washing of 5 contaminated mess tins
      followed by 5 uncontaminated mess tins. Porridge was used to simulate food
      residue and was mixed with Escherichia coli to produce bacterial contamination.
      Reduction of bacterial load on the mess tins was measured, as were subjective
      observations regarding the various systems. RESULTS: Bacterial load on
      contaminated tins is reduced when the 3-bowl system is used. Uncontaminated tins
      become contaminated in bowl 1, but this is then reduced in subsequent bowls.
      Disinfectant use, especially bleach, produced a marked reduction in bacterial
      load on contaminated and uncontaminated tins when used in bowl 2. Detergent is
      needed to remove grease, and a final rinse removes the smell of disinfectant.
      CONCLUSIONS: Overall, the most effective washing-up system in the laboratory was
      removal of most food residue with detergent in bowl 1, finish washing with bleach
      until visibly clean in bowl 2, and a final rinse in drinkable water in bowl 3.
      This system has advantages over the established 3-bowl system by getting mess
      tins clean more easily, killing potentially harmful bacteria, and removing the
      smell and taste of disinfectant.

PMID- 16805146
TI  - Physical and medical characteristics of successful and unsuccessful summiteers of
      Mount Everest in 2003.
AB  - OBJECTIVES: To describe physiological attributes (height, weight, sex, resting
      heart rate, etc.) of climbers attempting to summit Mt Everest and to investigate
      differences between successful and unsuccessful summiteers. METHODS: One-hundred
      thirteen Everest climbers were surveyed by questionnaire before and after the
      spring 2003 climbing season. Climbers' previous high-altitude climbing experience
      and physical characteristics were recorded, as well as health before and during
      expedition, medication used, body weight before expedition and after summit
      attempt, and ultimate summit success or failure. RESULTS: The most common
      afflictions among climbers were cough, diarrhea, nausea, and vomiting, and the
      most common medications used were acetazolamide, aspirin, and antibiotics.
      Average postacclimatization, presummit "rest" altitude was 4571 m, and average
      weight carried 10.7 kg. Average body mass loss during expedition, regardless of
      success, was 7%. CONCLUSIONS: Oxygen use and existence of gastrointestinal
      disorders are strongly correlated with success in summiting Mt Everest. On the
      other hand, a history of acute mountain sickness before the attempt is correlated
      with failure in summiting Mt Everest. Several other factors were found to be
      marginally correlated with chance of success, but the power of the study was
      limited by a low postsummit attempt questionnaire return rate (34%).

PMID- 16805147
TI  - A new technology for reducing shear and friction forces on the skin: implications
      for blister care in the wilderness setting.
AB  - OBJECTIVE: It is well known that physical trauma to skin caused by repetitive
      friction is a primary component of blister formation. Although friction blisters
      in a wilderness setting particularly occur on the feet and ankles, they often
      form on the hands and fingers during such activities as white-water rafting,
      kayaking, and canoeing. These blisters are often incapacitating and can have
      disabling consequences. This article describes laboratory and clinical
      experiments testing the efficacy of a new bandage technology in reducing shear
      and friction forces on the skin. METHODS: A custom-made apparatus was used in a
      laboratory setting to measure and compare the surface coefficient of friction of
      11 bandages. In addition, a controlled clinical study was conducted on 15
      healthy, able-bodied female subjects (mean age 35 years), where the same
      apparatus was used to measure the coefficient of friction of the skin over the
      medial tibial cortex with and without the new technology device in place.
      RESULTS: This laboratory study demonstrated the new device to have the lowest
      surface coefficient of friction of any bandage tested (0.57). For example, the
      common product Moleskin was 21% higher (0.67), with all other products testing at
      least 64% higher (>0.94). In the clinical study, the new technology device
      reduced the coefficient of friction on the skin by 31% (0.225 vs. 0.327), and
      this difference was statistically significant (P < .001). CONCLUSIONS: A bandage
      containing a new technology demonstrated the lowest surface coefficient of
      friction of any bandage tested. In addition, clinical tests performed with the
      same bandage demonstrated significant reduction of the coefficient of friction on
      the skin.

PMID- 16805148
TI  - Toxicodendron dermatitis: poison ivy, oak, and sumac.
AB  - Allergic contact dermatitis caused by the Toxicodendron (formerly Rhus) species
      poison ivy, poison oak, and poison sumac-affects millions of North Americans
      every year. In certain outdoor occupations, for example, agriculture and
      forestry, as well as among many outdoor enthusiasts, Toxicodendron dermatitis
      presents a significant hazard. This review considers the epidemiology,
      identification, immunochemistry, pathophysiology, clinical features, treatment,
      and prevention of this common dermatologic problem. Recent research in prevention
      is emphasized, and resources to help in the identification of plants are provided
      in the bibliography. The literature was searched using a MEDLINE query for
      "Toxicodendron dermatitis", and the identified article bibliographies were
      searched as well.

PMID- 16805149
TI  - Patellofemoral pain syndrome in Tibetan Buddhist monks.
AB  - Patellofemoral pain syndrome is a common diagnosis in athletes and especially
      runners. This article discusses 3 cases of patellofemoral pain caused by
      pronounced inactivity and prolonged knee hyperflexion at altitude in a unique
      population of Tibetan Buddhist monks. In this case, the monks responded well to a
      program of activity modification and exercises.

PMID- 16805150
TI  - Recurrent sagittal sinus thrombosis occurring at high altitude during expeditions
      to Cho Oyu.
AB  - We report the case of a previously healthy 32-year-old man presenting with severe
      headache on 2 separate expeditions to Cho Oyu (8201 m). No brain imaging was
      performed after the first expedition. On the second expedition, thrombosis of the
      superior sagittal sinus was detected. Investigations for hypercoagulable states,
      including polycythemia, were negative. He had no neurological symptoms except
      headache, vomiting, and slight drowsiness. In retrospect, there are strong
      indications that cerebral thrombosis caused his headache on the first expedition
      as well. Severe headache occurring at high altitude that persists despite
      adequate treatment for high-altitude cerebral edema should raise suspicion of a
      cerebrovascular disorder.

PMID- 16805151
TI  - High-altitude pulmonary edema presenting 18 hours after descent.
AB  - High-altitude pulmonary edema (HAPE) is a potentially life-threatening condition
      that is rapidly and definitively treated by descent. We report a case of
      worsening HAPE, presenting more than 18 hours after descent to sea level. The
      patient was treated with diuretics, calcium channel blockers, and oxygen and
      improved during a 24-hour observation period. To our knowledge, this is the first
      reported case of HAPE symptoms increasing after descent from altitude.

PMID- 16805152
TI  - Carbon monoxide toxicity at high altitude.

PMID- 16805153
TI  - Staying the course: the Captain's Log continues.
AB  - This paper introduces the reader to the context for the papers in this journal
      supplement by describing the background and task assigned to the authors, a short
      history of the development of the field of literacy and health in Canada, some
      recent developments and opportunities, some information on the nature and
      magnitude of the issue, and an overview of the supplement. The publication
      results from the Second Canadian Conference on Literacy and Health. Authors were
      asked to summarize what was learned at the conference, what we need to know, and
      what we need to do to move the field forward in relation to the themes of the
      conference. The four themes were: Building Best Practices in Literacy and Health;
      Focusing on Language and Culture; Building Knowledge in Literacy and Health; and
      Building Healthy Public Policy.

PMID- 16805154
TI  - Critical analysis on best practices in health literacy.
AB  - From a holistic perspective, health literacy is a requirement for the well-being
      of entire populations. It moves beyond the focus on individuals to consider the
      role of organizations and systems. This perspective offers a context for
      discussing best practices in health literacy, and implications for research and
      policy development. This paper offers an overview of the best practices that were
      presented at the Second Canadian Conference on Literacy and Health. It discusses
      clear writing in some detail because it was emphasized at the conference. It also
      considers practices that were addressed less emphatically, such as oral
      communication between patients and health care professionals, training for health
      care professionals, non-written means of communication (such as video), and
      building capacity through action-research. The paper critiques some practices. It
      also notes the lack of research on the links between health literacy and oral
      understanding, on the impact of verbal and non-written interventions, and on the
      effectiveness of these practices on the health outcomes of the population. It
      briefly discusses policy issues and suggests some future directions.

PMID- 16805155
TI  - Literacy and health practice resources.

PMID- 16805156
TI  - Social capital, health, and Francophone minorities.
AB  - The goal of this article is to outline the analytical perspectives of the concept
      of social capital regarding health and health management. Social capital, as
      defined in terms of social networks and resources, has a positive impact on a
      number of areas, notably the health, well-being, and social and economic
      development of communities. It is also a useful tool for implementing social
      policy, especially for marginal populations, the elderly, social assistance
      payments, etc. An action strategy based on the support and development of
      networks is the key to achieving the social development, health, and well-being
      of populations. The social ties promoted by these networks provide people with
      social, cognitive, and emotional support. This has a direct impact on their self
      esteem and sense of personal achievement. They also facilitate access to social
      resources, including social advancement opportunities. In this paper, we examine
      the vitality, determinants of health, and health management of Canada's minority
      Francophone communities.

PMID- 16805157
TI  - Culture-based literacy and Aboriginal health.
AB  - This is a summary report of the Aboriginal content of the Language and Culture
      theme at the Canadian Public Health Association's Second Canadian Conference on
      Literacy and Health. Our key premise is that Indigenous conceptualizations of
      literacy need to build on Indigenous understandings and perspectives. We support
      this premise through a review of the relevant literature in the disciplines of
      Aboriginal literacy, Indigenous education, health literacy, health promotion, and
      knowledge translation and our synthesis of the presentations, workshops, and
      discussions at the meeting. Key emergent themes include: the unique and
      culturally determined ways in which Aboriginal peoples and their languages
      conceptualize learning, education, and health; and the recognition that self
      determination of language and learning are human rights. Aboriginal concepts of
      and approaches to literacy naturally link to and overlap with Aboriginal concepts
      of and approaches to health. The paper includes an overview of gaps in the field
      and an example of the way that research and practice can be brought together in
      the context of one First Nations community.

PMID- 16805158
TI  - Health literacy within the reality of immigrants' culture and language.
AB  - The Second Canadian Conference on Literacy and Health addressed issues of health
      literacy, culture, and linguistic diversity. This article aims to introduce the
      presenters' ideas, reports of the learners' discussion, and attendees'
      recommendations. There is also a literature review of the links between health
      literacy and use of health services among newcomers in Canada. Newcomers to
      Canada tend to be unfamiliar with the Canadian health care system in terms of
      navigating needed services and/or seeking health-related information. Health
      professionals report difficulties in communicating effectively with these
      populations about risk-taking behaviours. Educational resources and approaches
      only partially reach people from cultural minorities. E-health information does
      little for those with language and literacy limitations. Barriers to accessing
      information, specifically written material, are widely reported. Consequently,
      many ethnocultural groups do not participate in health promotion initiatives.
      Among newcomers to Canada, the problems of adapting to a new health culture are
      linked to both a lack of information about the new health care available and
      subsequently their experience with that health care system. There is also a
      structural barrier. It includes lack of access to preventive health care services
      and the lack of a formal and informal support network. This results in less
      effective use of these preventive services. Linguistic, religious, and cultural
      factors contribute to the newcomers' social isolation. Multidisciplinary work to
      enhance health literacy and awareness about health and healthy lifestyles will
      permit ethnocultural populations to develop their potential and more fully enjoy
      their lives in Canada. Simultaneously, health educators should have the
      opportunity to realize their limitations and challenges in dealing with the
      complexity of providing health education to this population. There remain gaps in
      our knowledge about the access and use of health services by subpopulations from
      different cultural groups in terms of their gender, learning practices, ways of
      navigating services, and help-seeking behaviours.

PMID- 16805159
TI  - Building knowledge in literacy and health.
AB  - Health and literacy share an interesting relationship. The complexities of the
      relationship between literacy and health need to be recognized by policy-makers
      and practitioners to dispel myths, reduce stigma attached to low literacy, and
      empower disadvantaged groups. As we engage in building knowledge in the field,
      there is a need for multi-sectoral collaboration, both quantitative and
      qualitative information, and more effective ways to communicate with and educate
      people with low literacy. At the Second Canadian Conference on Literacy and
      Health, research reported indicates that in terms of what we know, the field has
      focussed on: linking literacy and health; examining intervention programs;
      exploring e-health and rural health; evaluating programs; and empowering people.
      In exploring what we need to know, researchers at the conference identified the
      need to understand: the extent of literacy sensitivity among health care
      providers in diverse settings; the impact of using plain language and readability
      formulas; the effectiveness of approaches to instructing literacy; and the
      incorporation of health content and health literacy goals into literacy
      instruction. Further, we need to create accessible ways of sharing knowledge in
      the field to build and strengthen existing multi-sector partnerships within and
      between communities.

PMID- 16805160
TI  - Building healthy public policy.
AB  - Policies in literacy and health need to address two perspectives: how basic
      literacy skills influence the health of populations and individuals; and health
      literacy--the degree to which individuals have the capacity to obtain, process,
      and understand basic health information and services needed to make appropriate
      health decisions. There are three potential areas for action to improve literacy
      and health literacy: the health system, the education system, and within the
      broader sphere of culture and society. Despite some increasing attention in the
      last 20 years, low literacy levels remain a major problem in Canada. Policies
      need to be sensitive to culture, especially among Aboriginal peoples,
      Francophones and new Canadians. Public policies are needed to: Improve literacy
      outcomes (for example, support for a pan-Canadian literacy strategy, early
      childhood education and family literacy programs, and efforts to reduce high
      school drop out). Improve health literacy (for example, support integrated policy
      and program development across sectors, integrated research and knowledge
      translation initiatives, and efforts to build links between literacy and health
      networks). Reduce disparities by strengthening levels of literacy and health
      literacy among vulnerable groups.

PMID- 16805161
TI  - As the ship sails forth.
AB  - This concluding article comments on what we learned from the conference, what we
      still need to know, and what we need to do now. It describes what participants
      said about the impact of the conference and the follow-up steps that have been
      taken so far. In terms of what we learned, there was agreement on the importance
      of culture in understanding literacy and health literacy; the importance of
      context; the integral relationship between literacy and health literacy and the
      concept of "empowerment;" the value of efforts to improve health through literacy
      and health literacy; and the need for collaboration. We need more and better
      information on how our various efforts are working; the cost of low literacy; the
      links between health, education, and lifelong learning; the needs and strengths
      of Aboriginal people, and the perspectives of Francophone and ethnocultural
      groups. Specific topics worthy of pursuit are suggested. They are followed by a
      list of recommendations from the conference related to focussing on language and
      culture, and to building best practices, knowledge, and healthy public policy.
      The paper presents some findings from the conference evaluation, which suggests
      that the conference met its goals. It concludes by reporting on actions that have
      been taken to implement the conference recommendations, including the
      establishment of a Health Literacy Expert Committee and the submission of several
      funding proposals.

PMID- 16805162
TI  - General literacy and health resources.

PMID- 16805163
TI  - Community-based antenatal and perinatal interventions and newborn survival.
AB  - BACKGROUND: As part of the millennium development goal (MDG) 4 to reduce by two
      thirds the mortality rate among children under five, neonatal mortality rate
      (NMR) needs to be reduced by half. This is a selective review of the literature
      of the morbidity and mortality patterns among newborns as well as cost-effective
      interventions and community aspects of newborn care. METHODS: Documented causes
      of morbidity and mortality among newborns were examined in the overall context of
      developing and developed countries. Cost-effective interventions that have been
      proven to be inexpensive with evidence or potential to save newborns' lives by
      international agencies concerned with health, journals and other publications
      were reviewed. Community aspects of newborn care and what is required at the
      individual, household and community levels to reduce neonatal morbidity and
      mortality were also reviewed. RESULTS: A score of recent publications by the
      World Health Organization (WHO), Save-the-Children, United Nations Children's
      Fund (UNICEF), journals, and other scientific publications reported consistently
      that neonatal mortality constitute 40-70% of deaths in infancy and that 99% of
      these deaths occurred in developing countries, with highest neonatal mortality
      rates (NMRs) in sub-Saharan Africa. The global burden of newborn illness shows
      that a disparity of up to 30-folds exists between countries with highest and
      lowest NMRs. Four million babies die in developing countries and about 42% of
      these deaths are due to infections. Other major causes include perinatal asphyxia
      (21%), birth injuries (11%), prematurity and low birth weight (10%) and
      congenital abnormalities (11%). It was also observed that two-thirds of the
      deaths in the neonatal period occur in the first week; among these deaths, two
      thirds occurred within the first 24 hours. Review findings also revealed that an
      integrated, proven and cost-effective intervention such as the mother-baby
      packages incorporated into a functional and sustainable healthcare delivery
      system and improved household practices will save newborns' lives. Reports showed
      that to achieve meaningful development, neonatal mortality will need to be
      reduced in developing countries. CONCLUSION: Programmes that are necessary for
      the reduction in neonatal morbidity and mortality rates are for countries to
      employ rational mix of quality clinical services, effective public health
      measures and inexpensive community-based interventions in public and private
      sectors and to scale-up known cost-effective interventions.

PMID- 16805164
TI  - The use of external fixators: a review of literature and experiences in a
      developing world.
AB  - BACKGROUND: The introduction of external fixation devices has brought significant
      improvement in the management of complex open fractures. Its importance and
      versatility ranges from its use as temporary fixation device in fractures with
      soft tissue and vascular injuries to its use in definitive correction of limb
      length deformities and congenital malformations. It avoids extensive soft tissue
      damage and enhances easy management of associated soft tissue injuries. METHOD:
      This was an overview of the clinical experience at the University of Calabar
      Teaching hospital and a review of literature. RESULT: The paper highlight the
      usefulness of external fixation devices and the need to encourage its use in the
      developing world. It also stresses the constraints encountered in a Nigerian
      teaching hospital. CONCLUSION: A call is made to all surgeons particularly those
      in rural areas to make use of this simple appliances after due training.
      Government should equip the hospitals with these tools and encourage the
      fabrication of such in our environment.

PMID- 16805165
TI  - Computer technology and the surgeon: what the resident needs to know.
AB  - BACKGROUND: Computer technology is now a well established resource in medicine
      and medical sciences. Surgery in developed countries has taken great advantage of
      this resource. This review is intended to highlight important aspects of
      computers in surgery and also encourages surgeons in Nigeria to acquaint
      themselves with its influences. METHODS: Publications from local and
      international journals as well as standard surgical texts were reviewed. RESULTS:
      The role of computers in surgery spans the areas of patient care, training,
      research, communication as well as surgical administration. Though a compliment
      to the surgeon, it has its problems including overwhelming information requiring
      careful scrutiny; computer fraud, hacking and viruses; copyright laws; the
      'threat' of a well-informed patient population; and the risk of over dependence.
      Surgery in Nigeria and most of African is yet to maximize its benefits.
      CONCLUSION: The application of computers in surgery will in the near future make
      surgical knowledge and practice become more simplified and less time with
      increased productivity will be required even for highly technical procedures.

PMID- 16805166
TI  - A controlled study of anxiety and depression in mothers of children with learning
      disability in Lagos, Nigeria.
AB  - BACKGROUND: Parents of children with learning disability have been reported to
      suffer great stress and frustration due to increased burden of care. The
      manifestation of stigmatization by familial environment and the collective effect
      of the children with adverse impact on mothers predispose them to mental shock or
      a variety of neurotic symptoms and other psychiatric conditions including anxiety
      and depression. The objectives of the study were: to determine the general Health
      Questionnaire (GHQ) score of mothers of children with learning disability. To
      identify sociodemographic variables and to assess anxiety and depression in them.
      METHODS: Using structured questionnaires between March and May 2002, 106 mothers
      of children with learning disability in a Mentally Handicapped Home for children
      in Lagos, Nigeria were assessed and compared with mothers of normal healthy
      children in Lagos. RESULTS: The mean age of the subjects was 40.0 +/- 6.6 years.
      More of the subjects (26.4%) compared with mothers of normal healthy children
      (9.9%) had a high GHQ score and high levels of anxiety (25.5%) and depression
      (10.4%). Marital difficulties were associated with learning disability.
      CONCLUSION: Mothers of children with learning disability are prone to emotional
      and psychological disorders. In order to improve the well-being of children with
      learning disability, there is need to look into the mental and physical health of
      mothers. Early and prompt treatment of associated anxiety and depression will no
      doubt help the children.

PMID- 16805167
TI  - Ischaemic heart disease in Aminu Kano Teaching Hospital, Kano, Nigeria: a 5 year
      review.
AB  - BACKGROUND: Socio-economic changes and rural urban migration have led to
      emergence of non-communicable disease including ischaemic heart disease (IHD) and
      many others. The actual prevalence of IHD in Nigeria is not known. The non
      communicable disease (NCD) survey sought to determine the prevalence of major
      risk factors, rather than the prevalence of the disease itself. The prevalence is
      generally considered low in Nigeria but the current impression about its
      importance stems mostly from anecdotal reports. We therefore set out to describe
      the prevalence as well as the spectrum of IHD at Aminu Kano Teaching Hospital,
      Kano. METHOD: Between July 2000 and June 2005, we reviewed the prevalence as well
      as the spectrum of presentation of IHD in Aminu Kano Teaching Hospital.
      Information was obtained from the medical records of patients in the medical unit
      of the hospital. Age, sex, diagnosis, risk factors for IHD, other relevant
      clinical and laboratory data and outcome of patients for myocardial infarction
      (MI) were extracted from the records. Data was analyzed using SPSS version 10.0
      software. RESULTS: There were 5124 medical patients admitted over the period
      under review, out of which 1347 had cardiovascular diseases. Forty six patients
      were diagnosed to have IHD giving it a prevalence of 0.9% of medical conditions
      and 3.4% of all cardiovascular cases. There were 33 males and 13 females (M : F =
      2.5:1). Twenty two patients (47.8%) had myocardial infarction, 14 (30.4%) had
      ischemic cardiomyopathy and 10 (21.7%) had angina. The patients consist of 41
      (89.1%) Nigerians, 3 (6.5%) Lebanese, 1 (2.2%) Indian and 1 (2.2%) Pakistani. The
      risk factors found were Hypertension in 37 (80.4%) of patients, diabetes in 16
      (34.8%), and Dyslipidaemia in 20 (43.5%). Others were cigarette smoking and
      obesity. CONCLUSION: IHD is an important cause of morbidity and mortality in our
      population. There is need for us to be on the alert and prepare ourselves to
      manage these cases. Focus should be on preventive cardiology.

PMID- 16805168
TI  - Echocardiography in the University of Port Harcourt Teaching Hospital: April 2000
      to March 2003.
AB  - BACKGROUND: Echocardiography is a cheap and non-invasive technique for the
      investigation of cardiac diseases with reliable levels of accuracy.
      Echocardiography services commenced in the Cardiac unit of the University of Port
      Harcourt Teaching Hospital (UPTH) in April 2000. There is a need to establish an
      accurate pattern of cardiac diseases seen in the centre based on echocardiography
      assessment. The aim of the study was to review the pattern of cardiac diseases
      diagnosed by echocardiography in the cardiology unit of the University of Port
      Harcourt Teaching hospital. METHOD: A prospective descriptive study of patients
      referred to the cardiology unit of UPTH for echocardiography for a variety of
      cardiac complain was done. Subjects had two dimensional and M-mode
      echocardiography assessment using a Siemens Sonoline SL 1 machine with a 3.5 MHz
      sector probe. RESULTS: One hundred and forty one subjects aged between 16-84
      years with a mean age of 44.2 +/- 11.5 years had echocardiography assessment over
      the three year period. Eighty two (58.2%) of the subjects were males while 59
      (41.8%) were females. Fourty eight (34.0%) of subjects had hypertensive heart
      disease, 28 (19.9%) had Cardiomyopathies, 13 (9.2%) had rheumatic heart disease.
      Pericardial disease, congenital heart disease and cor pulmonale was found in 6
      (4.3%), 2 (1.4%) and 1 (0.7%) respectively. Fourty three (30.5%) of subjects had
      normal findings on echocardiography. CONCLUSION: Hypertensive heart disease was
      found to be the most prevalent cardiac condition followed by the cardiomyopathies
      and rheumatic heart disease in that order. This trend is very similar to what
      obtains in sub Saharan Africa as documented by similar studies.

PMID- 16805169
TI  - Lipid profile of healthy adult Nigerians in Port Harcourt, Nigeria.
AB  - BACKGROUND: Hyperlipidaemia is a major cardiovascular risk factor for coronary
      artery disease, atherosclerosis, hypertension and stroke. It is thought that
      serum cholesterol levels are low in Nigerians as shown by results of a population
      survey done over twenty years ago. In addition the last national non communicable
      disease survey recorded a low prevalence of Hyperlipidaemia (4.0%) in Nigeria.
      With increasing urbanisation and socioeconomic improvement, changing population
      dynamics is expected to influence disease pattern and noncommunicable diseases
      are expected to rise. Thus there is a need to screen healthy adults for their
      lipid pattern in Port Harcourt a city with high population dynamics where such
      studies have not been previously reported. METHOD: A prospective descriptive
      population survey was carried out among healthy adults residing in Port Harcourt.
      A total of ninety two adults were screened after obtaining informed consent.
      Weight, height, blood pressure, fasting blood sugar and fasting lipid profile
      were measured. Results were analysed using simple statistical methods. RESULTS: A
      total of ninety two subjects were recruited into the study. Fourty seven (51.1%)
      of the subjects were males while fourty five (48.9%) were females. The age range
      of subjects was 24-59 years with mean of 38.84 +/- 8.36 years. The mean BMI was
      28.76 +/- 5.91 Kg/m2. There was no significant statistical difference between the
      mean BMI for males and females. The mean fasting blood sugar, mean total
      cholesterol and mean LDL cholesterol were 4.45 +/- 0.89 mmol/L, 4.76 +/- 1.06
      mmol/L and 3.65 +/- 0.89 mmol/L. The mean total triglyceride was 1.02 +/- 0.30
      mmol/L while the mean HDL was 0.90 +/- 0.25 mmol/L. There was an increase in
      total cholesterol with increasing age and an increase in total cholesterol and
      LDL cholesterol with increasing social class. Subjects with total cholesterol
      above 6.5 mmol/L constituted 31.52% of study subjects. Subjects with BMI between
      25-29 Kg/m2 made up 43.48% of subjects while 33.69% of subjects had BMI above 30
      Kg/m2. CONCLUSION: A high mean total and LDL cholesterol values were observed
      among healthy adults in Port Harcourt. The prevalence of obesity was also found
      to be high. There is a need for public health action to address these findings
      especially as high serum cholesterol levels have a direct correlation with
      coronary artery disease. Further large scale urban survey of non communicable
      diseases in the country is therefore necessary at this time.

PMID- 16805170
TI  - Blood pressure and pulse rate changes associated with cervical traction.
AB  - BACKGROUND: This study was carried out at the Physiotherapy unit of the
      University of Maiduguri Teaching Hospital, to observe the effects of continuous
      cervical traction for 10 minutes on arterial blood pressure and pulse rate.
      METHODS: Forty healthy subjects free of any cardiovascular complications,
      participated in the study. Systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and pulse rate (PR), were recorded before, during and after the
      application of cervical traction 10% body weight, using spty-pulse 2000
      Electronic sphygmomanometer. RESULT: Analysis of variance showed statistically
      significant (P < 0.05) increase in systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and pulse rate (PR) from 114.6 +/- 10.4 mmHg, 72.4 +/- 9.5 mmHg
      and 71.7 +/- 5.9 beats/min to 123.5 +/- 9.8 mmHg, 77.9 +/- 8.9 mmHg and 78.2 +/-
      5.7 beats/min respectively following traction. CONCLUSION: It is advised that
      clinicians should comprehensively assess all cardiovascular parameters of
      patients before applying cervical traction.

PMID- 16805171
TI  - Common causes of red eye presenting at an ophthalmic clinic.
AB  - BACKGROUND: Redness of the eye is a common ophthalmic symptom. The problem
      causing redness could arise from within or outside the globe. These range from
      cases of simple inflammation following itching and minor trauma for example, to
      severe cases like orbital cellulitis and tumours. Patients may not even be aware
      of the redness. The aim of this study is to highlight the common causes of red
      eye as seen in an outpatient department in an ophthalmic set up. This should be
      of immense help to the general medical practitioners to whom the patients often
      first present. METHODS: All patients presenting for the first time to Ladoke
      Akintola University of Technology Teaching Hospital over a four month period were
      screened. 117 had red eyes and were recruited. 125 eyes were found to be red. The
      characteristics of the redness were then studied to determine the cause. RESULTS:
      There was a male preponderance, M : F of 2:1. Persons 45 years and below, were
      most commonly involved 88 (66.67%). The most frequent cause of red eye was
      trauma, in 48 (41.03%) patients, followed by allergic conjunctivitis in 29
      (24.77%). The main causes of redness differed in different age groups and
      occupation. There was no case of angle closure glaucoma seen as a cause of
      redness. CONCLUSION: There are diverse causes of redness of the eye. Persons who
      are not eye specialists to whom patients with red eyes present first should be
      conversant with the causes, to know what action to take, especially when to refer
      to the eye specialist.

PMID- 16805172
TI  - Significance of platelet activation in sickle cell anaemia.
AB  - BACKGROUND: There is increasing evidence suggesting the contribution of platelets
      in the vaso-occlusive phenomena found in sickle cell anaemia. This study is aimed
      at using simple, inexpensive parameters to determine the role of platelets in the
      steady state and vaso-occlusive crisis state of Nigerian sickle cell anaemia
      patients. METHODS: The circulating platelet aggregate (CPA) ratio, platelet
      factor-3 availability (PF-3) and platelet counts of 60 adult Nigerian sickle cell
      anaemia patients were studied. RESULTS: The CPA ratio in the sickle cell anaemia
      (SCA) patients in steady state (SS) was 0.93 +/- 0.05, 0.89 +/- 0.04 during vaso
      occlusive crisis (VOC) and 0.98 +/- 0.02 in the control group (C). The values in
      the vaso-occlusive crisis and in steady state were significantly lower than in
      the control group (P < 0.05). PF3 availability in steady state and vaso-occlusive
      crisis were 29.7 +/- 4.0 secs and 28.4 +/- secs respectively. The times are
      significantly shorter when compared with the control group with a time of 36.2 +/
      4.3 secs (P < 0.05). There was however no significant difference between the two
      sickle cell groups. Platelet count was significantly raised in the steady state
      patients 224.3 +/- 46.3 x 10(9)/L when compared with controls of 196.6 +/- 39.3 x
      10(9)/L (P < 0.05). There was a significant fall during VOC to 140.6 +/- 36.3 x
      10(9)/L (P < 0.05). The difference between the two sickle cell groups is
      significant (P < 0.05). CONCLUSION: This study indicates varying degrees of
      partial activation of platelets in vivo in the steady state and vaso-occlusive
      crisis state of sickle cell anaemia. It support's a contribution of platelet to
      the vascular occlusion that underlies much of the morbidity in the disease.

PMID- 16805173
TI  - Biochemical and haematological assessment of workers exposed to some petroleum
      products in Enugu Urban, Enugu State, Nigeria.
AB  - BACKGROUND: Exposure to petroleum product(s) occurs during extraction, refining,
      transportation and utilisation. Surprisingly, this relatively common hazard has
      received little public recognition. We therefore studied the adverse effects of
      petroleum products among occupationally exposed liquefied petroleum gas and
      histochemical workers in Enugu Urban, Nigeria. METHODS: Eight
      industries/departments were surveyed. Sixty workers were tested for some
      biochemical and haematological parameters (phosphatases, transaminases, complete
      blood count, erythrocyte sedimentation rate), were analysed, using standard
      methods. Also, 30 age and sex-matched apparently healthy subjects served as the
      control group. RESULTS: When the test and control results were compared, there
      were statistically significant differences (p < 0.05) in: (1) haematocrit,
      reticulocytes, erythrocyte sedimentation rate, platelet, lymphocyte, monocyte,
      alkaline phosphatase, aspartate transaminase, alanine transaminase among
      liquefied petroleum gas workers and (2) haemoglobin, haematocrit, erythrocyte
      sedimentation rate, platelets, neutrophil, lymphocyte, monocytes, acid
      phosphatases and alkaline phosphatase among histochemical workers. Overall, there
      was statistically significant decrease (p < 0.05) in most of the parameters among
      the test subjects when compared with the control group. Blood films of the
      workers revealed mild to moderate hypochromia, anisocytosis and poikilocytosis
      while the controls were normocytic and normochromic. CONCLUSION: We conclude that
      exposure to petroleum products adversely affects biochemical and haematological
      parameters. Hence, improved working conditions are recommended.

PMID- 16805174
TI  - Impaired acidification of urine in children aged two months to two years with
      acute gastroenteritis complicated by acidosis.
AB  - BACKGROUND: In some children with acute gastroenteritis and acidosis, the urine
      pH may be abnormally high thus simulating distal Renal Tubular Acidosis (dRTA).
      This inability to acidify urine properly in the presence of metabolic acidosis
      has been shown to be due to poor delivery of sodium to the distal nephron which
      prevents full excretion of a hydrogen ion load, instead of an intrinsic defect in
      the ability of the distal tubule to acidify urine. The aim of this study is to
      determine the prevalence of transient urinary acidification defect in children
      aged two months to two years with acute gastroenteritis, dehydration and
      acidosis, and the relationship between urine pH and urine sodium concentration.
      METHOD: A prospective study of children aged two months to two years admitted for
      the treatment of acute gastroenteritis and dehydration at the Children's
      Emergency Ward (CHEW) of the University of Port Harcourt Teaching Hospital,
      Rivers State. RESULTS: Of the 196 children (140 males and 56 females) studied
      with spontaneous acidosis which developed as a result of acute gastroenteritis,
      seventy-three of them had impaired acidification of urine, giving a prevalence of
      37.2%. There was no significant difference in the age, duration of symptoms,
      degree of acidosis, degree of dehydration and serum potassium concentration
      between the children with impaired and those with proper urine acidification.
      Those with impaired acidification of urine however had a significantly lower
      serum sodium and urine sodium concentrations and a significantly higher urine
      potassium concentration and urine anion gap than those children with proper urine
      acidification. All urine samples with sodium concentration less than or equal to
      25 mmol/L (52) had urine pH greater than 5.5. CONCLUSION: Mere presence of
      acidosis and high urine pH should not lead to a diagnosis of Distal Renal Tubular
      Acidosis (dRTA). The urine anion gap (UAG) should be calculated using the
      formula: urine [Na+] + [K+] [Cl], and if negative, it suggests a high ammonium
      excretion, which makes the diagnosis of dRTA unlikely.

PMID- 16805175
TI  - Benefit of modified plasmapheresis in the management of myasthenia gravis: a case
      report.
AB  - BACKGROUND: Myasthenia gravis is an autoimmune disease condition caused by the
      generation of antibodies against the acetylcholine receptor sites at the
      neuromuscular junction. The treatment modalities include anticholinesterase
      drugs, corticosteroids, immunotherapy, thymectomy and plasmapheresis. However,
      because of the poor financial state of our patients and the dearth of appropriate
      equipment in our centres modifications are made to standard treatment modalities
      including plasmapharesis. METHOD: We report a case of myasthenia gravis who was
      on various occasions on neostigmine, pyridostigmine and prednisolone. After about
      18 months of treatment, he developed myasthenic crises on two occasions. He was
      admitted in the ICU for respiratory support where he also had modified
      plasmapheresis. RESULTS: The patient had remarkable improvement following the
      modified plasmapheresis with reversal of symptoms of the myasthenic crises.
      CONCLUSION: In the absence of facilities for standard plasmapheresis in this
      environment, the use of modified plasmapheresis is hereby recommended.

PMID- 16805176
TI  - Chronic intestinal obstruction due to rectosigmoid endometriosis: a case report.
AB  - BACKGROUND: Intestinal endometriosis is not commonly reported in Nigeria and
      Africa. This paper presents a case of chronic intestinal endometriosis in a young
      Nigerian woman presenting with features of chronic intestinal obstruction.
      METHOD: The case records of a 29-year old Nigerian female, who presented with
      chronic intestinal obstruction secondary to endometriosis at the Olabisi Onabanjo
      University Teaching Hospital (OOUTH) Sagamu, Nigeria and literature review on the
      subject using medline and manual library search is presented. RESULT: A young
      woman presented with a three- month history of progressive abdominal distension
      and worsening constipation. Examination revealed a grossly distended abdomen,
      slightly tense but no area of tenderness. Bowel sounds were slightly exaggerated.
      A plain radiograph of the abdomen showed features of small and large bowel
      obstruction. A diagnosis of chronic large bowel obstruction was made. She was
      found to have a stricture in the rectosigmoid at laparotomy. Hartmann's resection
      was done. Histologically, the stricture was due to endometriosis. Subsequent
      closure of colostomy and re-establishment of intestinal continuity gave excellent
      results. CONCLUSION: A young Nigerian female diagnosed with chronic intestinal
      obstruction due to rectosigmoid endometriosis was successfully treated. Though
      this condition is believed to be relatively uncommon in Nigeria, there is a need
      for a high index of suspicion, to ensure early diagnosis.

PMID- 16805177
TI  - Gigantomastia complicating pregnancy: a case report.
AB  - BACKGROUND: Mammary gigantism is a rare, cosmetically embarrassing complication
      of pregnancy that may ulcerate and have potentially fatal bleeding. METHODS: A
      case report of a 20-year old primigravida with bilateral massive breast
      enlargement is presented to highlight the clinical presentation and management
      challenges of the condition. RESULTS: She was treated with local debridement,
      bromocriptine, antibiotics and blood transfusion with good results. The pregnancy
      however terminated at 27 weeks of gestation. CONCLUSION: Gigantomastia is a rare
      complication of pregnancy, which may pose a major management challenge. A
      favorable outcome may be achieved with prompt recognition of the condition and
      conservative management in selected cases.

PMID- 16805178
TI  - Missed diagnosis of amoebic liver abscess: a case for forward clinical reasoning.
AB  - BACKGROUND: Increasingly, a wrong diagnosis is made and wrong investigations and
      treatment ordered, because the doctor uses one or two symptoms to jump into a
      premature conclusion, without consideration of the totality of a patient's
      presentation. This is not forward clinical reasoning. Forward clinical reasoning
      is based on a systematic approach to patient's problems. The objective of this
      paper is to use a real case to illustrate the pitfall in ignoring forward
      clinical reasoning and how forward clinical reasoning serves the physician's and
      patient's interest better. METHOD/RESULT: The case of a 3 year old who had
      amoebic liver abscess but was wrongly diagnosed and treated for lobar Pneumonia
      with pleural effusion is highlighted. The sequence for forward clinical reasoning
      is used to show how the right diagnosis could have been arrived at. CONCLUSION:
      The correct diagnosis following sequential forward clinical reasoning saves time,
      money and life.

PMID- 16805179
TI  - After the oath, what's next? Residency programme in Nigeria and abroad; prospects
      and challenges.
AB  - BACKGROUND: In this article we discussed the prospects and challenges facing the
      newly graduated medical doctor in Nigeria. METHODOLOGY: The various opportunities
      available both at home and abroad were well discussed. Useful suggestions were
      given on how to succeed in one's chosen specialty. RESULTS: Despite the
      socioeconomic and political instabilities in the country, we should go to any
      extent to improve our knowledge whether at home or abroad. CONCLUSION: Whatever
      we do, wherever we go, we should always remember that this is our country and we
      must make every effort to make it a better place and a great nation.

PMID- 16805180
TI  - Clinical photographic quiz.

PMID- 16805181
TI  - [Germany as happy tobacco land].

PMID- 16805182
TI  - [Amputation in salami method].

PMID- 16805183
TI  - [When skin and bones reveal sprue].

PMID- 16805184
TI  - [Are so man cesarean sections necessary? (interview by Dr. Thomas Meissner)].

PMID- 16805185
TI  - [How many hormones does a man need?].

PMID- 16805186
TI  - [Support and comfort for those coping with pain, grief and isolation. We must all
      learn a new attitude to death].

PMID- 16805187
TI  - [Dying with dignity: The perspective of the family doctor].
AB  - The medical possibilities of keeping a patient alive with the aid of drugs and
      technical aids are constantly expanding. A more difficult decision that the care
      providing physician is called upon to make is: when is the point reached when
      further treatment no longer makes sense? From here on, the objective is to enable
      the patient to die with dignity,which entails allowing him/her and relatives the
      opportunity to take their leave of one another.

PMID- 16805188
TI  - [Medicine at life's end--the view of a palliative physician].
AB  - An international comparison reveals considerable differences in the legal
      constraints imposed upon a physician in his approach to the question of
      euthanasia and physician-assisted suicide. Despite the fact that surveys show 50
      80% of the German population to be in favor of active assistance for terminally
      ill patients wishing to end their lives, in 2004 the Bundesarztekammer (Federal
      Medical Association) confirmed its earlier rejection of active euthanasia and
      assisted suicide. Instead, Germany favors palliative medical measures that enable
      those whose death is imminent to take their leave with dignity.

PMID- 16805189
TI  - [Assisted dying in Germany: possibilities and where to draw the line--the legal
      view].
AB  - In Germany, the legal possibilities for withholding or withdrawing life
      preserving measures are based on four judgments by the Federal High Court, which
      forbid both the deliberate killing of a patient and physician-assisted suicide.
      Life-saving measures may be withheld or withdrawn only when this is in conformity
      with the declared will of the patient (as expressed, for example, in a living
      will, or by the patient's proxy), and when death is to be expected within the
      near future. If the process of dying has already begun, such a decision may be
      taken even when the expressed will of the patient is not known.

PMID- 16805190
TI  - [Pragmatic and effective treatment of painful neck].
AB  - Management of a patient with atraumatic neck pain is a complex task that
      necessitates a careful differentiation between harmless and risky but preventable
      courses (red flags), with account having to be taken of psychosocial and somatic
      factors. At the same time diagnostic measures need to be limited to the truly
      necessary, and the development of chronicity must be avoided. The very fact that
      the clinical significance of neck pain clearly takes second place to its
      psychosocial and health-economic aspects points up the need to explicitly draw
      attention to the rare dangerous courses.

PMID- 16805191
TI  - [Diabetes mellitus--differential diagnosis].
AB  - Differentiation of the various forms of diabetes is necessary for therapeutic
      reasons. Typical signs of type 2 diabetes are age over 40, obesity, and other
      markers for metabolic syndrome, a positive famitory, gradual development of the
      classical symptoms, and no evidence of ketosis. It is important to distinguish
      this from LADA (latent autoimmune diabetes of adulthood), a form of type 1
      diabetes mellitus. To establish this differential diagnosis antibody testing is
      employed. Antibody tests in patients with newly manifest diabetes make good sense
      when the clinical diagnosis is not unequivocal, that is, to distinguish it from
      type 2 diabetes, MODY diabetes, hereditary and secondary forms. At present,
      immunodiagnosis is used too often in unambiguous cases of type 1 diabetes, but
      too rarely in supposed type 2 diabetes. As a rule, LADA patients are GADA
      positive. If MODY diabetes is suspected, a genetic examination is indicated. In
      patients with GDM, antibody testing with GADA makes sense, in particular in slim
      patients receiving insulin treatment, since these patients have a high risk for
      developing a postpartum diabetes already in the first years.

PMID- 16805192
TI  - [How to deal with this patient?].

PMID- 16805193
TI  - [Counseling network for patients to be organized].

PMID- 16805194
TI  - [Pharmacists want to assume penalty].

PMID- 16805195
TI  - [Progress for patients with osteoporosis].

PMID- 16805196
TI  - [Better prognosis for stroke patients].

PMID- 16805197
TI  - [Atherosclerosis actually declines].

PMID- 16805198
TI  - [10 minute consultation. Crohn disease as suspected diagnosis].

PMID- 16805199
TI  - [Diagnosis at a glance: It is only a stork bite].

PMID- 16805200
TI  - The molecular biology of pulmonary metastasis.
AB  - Curing cancer requires the treatment of metastatic disease. Whether this is a
      patient with advanced disease and clinically apparent metastases, or if the
      patient with localized disease is at risk for development of dissemination,
      failure to control metastasis will result in a poor outcome. Here, we have
      presented a molecular guide to our current understanding of the processes
      underlying metastasis. Experimental clinical trials designed to further the
      understanding of metastasis are often limited by selection of patients with
      advanced disease. Therefore, our understanding of the processes involved in the
      metastatic cascade is limited by the availability of comprehensive experimental
      model systems. The study of metastasis relies most heavily on xenografts, tumors
      using human cell lines, or tumor tissue that can grow in mice. These models
      present a limited recapitulation of the patients. Xenograft models require some
      degree of immunosuppression on the part of the host, because mice with native
      immune systems will reject transplanted human tumors, preventing their growth. As
      a result, mice with immune defects ranging from depleted T cells (nude mice) to
      absent T, B, and NK cells (SCID-Beige) are used as hosts. As the evasion of the
      immune system is a key function demonstrated by the metastatic cancer cell,
      xenograft models, by necessity, subvert this step. Furthermore, recent studies
      have established that angiogenesis in transplanted tumors is different than in
      native tumors, further highlighting the limitations of these models. With these
      limitations, studies of metastasis may require development of models of
      autochthonous tumors, that is, tumors originating in the study animals. A number
      of cell lines of autochthonous murine tumors have been established that generate
      metastatic disease after implantation into mice. Moreover, some transgenic
      animals spontaneously develop metastatic tumors that, although occurring in
      genetically engineered animals, may represent the most complete model from early
      development to late effects. Finally, a very promising field of autochthonous
      tumor studies lies in work with companion animals (pets). Some dogs will have
      cancer, often with striking similarities to those of their human counterparts.
      These pets may represent an important study group, because they have
      autochthonous tumors, occurring spontaneously, in an outbred population. In all
      of these cases, the tumor, new vasculature, and the immune system are syngeneic
      with the host. In addition to the advances in model systems, advances in
      technology will further our understanding and ability to combat metastatic
      disease. As demonstrated, genomics is proving to be a powerful tool in
      identifying those at risk for metastasis. From these genetic signatures,
      molecular targets may be deduced from the genes altered in patients with poor
      prognoses. Furthermore, other molecular tools such as proteomic analysis may
      provide further information. Clearly, therefore, a synthesis of different
      technologies and complimentary information will be required to target metastases
      and improve the outcome for patients affected by them.

PMID- 16805201
TI  - Preoperative workup and postoperative surveillance for patients undergoing
      pulmonary metastasectomy.
AB  - The workup of patients suspected of having pulmonary metastases is complicated by
      the fact that a high percentage of pulmonary metastases are 6mm or less at
      presentation. Helical CT scans and high-resolution CT scans currently miss many
      of the lesions eventually detected at thoracotomy and many of the lesions
      detected are benign. The follow-up of patients after pulmonary metastasectomy is
      a controversial topic because of the lack of evidence-based practice guidelines.
      Though it is unlikely that current follow-up recommendations will ever be tested
      in randomized controlled trials, meta-analyses of existing retrospective data
      could improve the quality of the existing literature.

PMID- 16805202
TI  - Surgery for colorectal and sarcomatous pulmonary metastases: history, current
      management, and future directions.
AB  - This article provides a historical review of metastasectomy, reviews current
      surgical management approaches, and proposes what direction future research must
      take to determine whether there is a survival advantage associated with pulmonary
      metastasectomy and how best to integrate metastasectomy with medical therapies,
      primarily induction, and adjuvant chemotherapy.

PMID- 16805203
TI  - Lymphadenectomy in metastasectomy.
AB  - Although surgery for pulmonary metastases does not benefit a significant number
      of patients, PM should continue to be offered to patients whose primary tumor is
      controlled and who have acceptable operative risks. For a survival benefit to be
      achieved, all extrathoracic and pulmonary metastases must be amenable to complete
      surgical resection. We have shown that the presence of metastatically involved
      lymph nodes discovered during PM adversely effects survival in patients
      undergoing curative PM. We therefore continue to recommend complete mediastinal
      lymphadenectomy at the time of PM to define the patient's prognosis and perhaps
      to guide adjuvant therapy.

PMID- 16805204
TI  - Combined resection of liver and lung metastases for colorectal cancer.
AB  - This article evaluates the available evidence for the efficacy of combined liver
      and lung metastasectomy. In addition, selection criteria identifying patients
      most likely to benefit from this approach are discussed. Surgery offers the only
      possibility for prolonged survival and is occasionally curative.

PMID- 16805205
TI  - Minimally invasive techniques for managing pulmonary metastases: video-assisted
      thoracic surgery and radiofrequency ablation.
AB  - Therapeutic pulmonary metastectomy is accepted therapy for pulmonary metastases.
      However, more than 50% of patients who undergo this treatment will experience
      recurrences, many within the same lobe. Minimally invasive approaches provide an
      option for therapy that minimizes morbidity and, in the case of RFA, preserves
      pulmonary function. The long-term results of RFA, even for non-small cell lung
      cancer, are not yet determined. Resection using a VATS or open approach should
      continue to remain the standard of care.

PMID- 16805206
TI  - Pulmonary metastasectomy in pediatric patients.
AB  - This article describes the historical development of pediatric pulmonary
      metastasectomy but demonstrates that progress has been slow in understanding its
      proper applications. Because many pediatric metastatic tumors are rare, surgeons
      have grouped together patients of different histologies for the generation and
      analysis of case series. By examining tumor types individually, however, it is
      seen that certain histologies (adrenocortical carcinoma, alveolar soft part
      sarcoma, osteosarcoma) mandate surgical metastasectomy for patient survival.
      Other pediatric tumors (Wilms tumor, Ewing's sarcoma) are radiation sensitive,
      and the application of metastasectomy is controversial. In the case of still
      other types of tumor (neuroblastoma, differentiated thyroid cancer,
      rhabdomyosarcoma), metastasectomy is seldom performed except in highly unusual
      situations. Techniques for minimally invasive biopsy and for muscle-sparing
      thoracotomy are described for pediatric patients.

PMID- 16805207
TI  - Isolated lung perfusion for pulmonary metastases.
AB  - Isolated lung perfusion is an experimental surgical technique evaluated for the
      delivery of high-dose chemotherapy to improve 5-year survival after pulmonary
      metastasectomy. Extensive experimental work in animal models has demonstrated
      superior pharmacokinetics and efficacy compared with systemic therapy. Phase I
      clinical trials of isolated lung perfusion found a maximum tolerated dose**** of
      TNF-alpha, doxorubicin, cisplatin, and melphalan, whereas the combination of
      isolated lung perfusion with a complete metastasectomy was feasible. The
      combination of isolated lung perfusion and regional lung perfusion techniques
      needs further investigation.

PMID- 16805208
TI  - [Therapeutic aspects in coronary cardiac patients who suffer from sexual
      dysfunction in a cardiac rehabilitation program].
AB  - Sexual dysfunction is one of the severe consequences of acute coronary events.
      Rehabilitation programs should address this aspect of functioning that has
      important implications for the patient's quality of life. In order to improve
      patients' sexual functioning and improve their quality of life we developed a
      comprehensive model of sexual therapy designed specifically for cardiac patients
      undergoing rehabilitation program. This model integrates educational, supportive
      and cognitive-behavioral therapy with appropriate medication (such as viagra).
      The model is implemented in co-therapy by two sexologists, a social worker and a
      physician. An empirical study has shown the positive outcomes of this model. This
      article describes the model and reports case vignettes that exemplify its effects
      on cardiac patients in rehabilitation and their spouses.

PMID- 16805209
TI  - [Trends in management, morbidity and mortality of patients with acute myocardial
      infarction hospitalized in the last decade].
AB  - BACKGROUND: The diagnosis and management of acute myocardial infarction (AMI) has
      undergone major changes during the last decade. These changes reflect the results
      of numerous controlled clinical trials that established the basis for evidence
      based guidelines. AIMS: The aims of this study were to examine the trends in the
      characteristics, management and outcome of patients with AMI, hospitalized in all
      25 Intensive Care Units (ICCU) operating in Israel during the last decade (1994
      2004). METHODS: Data were derived from the biannual two-month national AMI/Acute
      Coronary Syndrome Israeli Surveys (ACSIS) performed in Israel. During the last
      decade, there was a continuous increase in the number of AMI patients admitted to
      the ICCU's operating in Israel - 999 AMI patients in 1994 and 1,534 in 2004. This
      increase was possibly due to shortening of hospital stay of AMI patients.
      RESULTS: The mean age of patients (64 years) did not change significantly in the
      last decade. The ICCU population has been characterized by an increasing number
      of octogenarians (7% in 1994 and 13% in 2004) and higher numbers of patients with
      past history of PCI, CABG, CVA and other comorbidities. There have been increases
      in the use of evidence-based medications during hospital stays and at discharge,
      reflecting greater adherence to guidelines. The "primary reperfusion" rate
      increased in the last decade from 60% in 1998 to 64% in 2004. The mode of
      reperfusion has changed in favor of primary PCI in 2004. In 1998, 88% of STEMI
      patients who underwent primary reperfusion were treated with thrombolysis and 12%
      by primary PCI while in 2004, 33% were treated with thrombolysis and 67% by
      primary PCI. The hospital course of patients with AMI in the last decade is
      characterized by better outcomes with reductions in rates of reischemia and
      reinfarction, cardiogenic shock, atrial fibrillation, VT/VF, and AV Block 2
      degrees - 3 degrees. The most striking change in the last decade is the
      significant reduction in short- and long-term mortality with 45% reduction in 7
      day mortality and 33% reduction in one-year mortality. CONCLUSIONS: This trend of
      better clinical outcomes and lower mortality in the last decade most probably
      relates to the use of evidence-based treatment and to better adherence to
      guidelines in the operating ICCUs in Israel.

PMID- 16805210
TI  - [Diabetics with normal coronary arteries: clinical features and prognosis].
AB  - BACKGROUND: Diabetic patients comprise a large proportion of patients referred
      for coronary angiography. Only a minority of these patients will be found to have
      normal coronary arteries. AIM: To characterize diabetic patients who have
      angiographically normal coronary arteries. METHODS: Case-control study based on a
      computerized database. RESULTS: Using our computerized database, 13,342
      consecutive patients referred for coronary angiography were identified. Diabetes
      mellitus was diagnosed in 24% of cases. Angiographically normal coronary arteries
      were found in 151 (5%) and 1228 (12%) of diabetic and non-diabetic patients,
      respectively (p<0.01). Diabetic patients with angiographically normal coronary
      arteries were matched with 155 diabetic patients who were catheterized on the
      same day but were found to have coronary artery disease. The median follow-up
      period was 1,774 days. The age of the diabetic patients with normal coronary
      arteries and diabetic patients with coronary artery disease was 5710 and 6410
      years old respectively (p<0.01). A total of 39% and 60% of diabetic patients with
      normal coronary arteries and with coronary artery disease respectively were
      males, (p<0.01). Dyslipidemia was diagnosed in 66 (43%) of the diabetic patients
      with normal coronary arteries and 87 (57%) of the diabetic patients with coronary
      artery disease (P<0.01). After controlling for age and sex, the finding of normal
      coronary arteries was associated with decreased mortality (OR: 0.47, 95% CI 0.23
      to 0.95). CONCLUSIONS: In diabetic patients referred for angiography it is
      unusual to find angiogrtaphically normal arteries. These patients have a
      relatively benign prognosis, as opposed to diabetic patients with evident
      coronary disease.

PMID- 16805211
TI  - [Primary angioplasty for acute myocardial infarction in octogenarian patients].
AB  - This study aimed to evaluate clinical outcomes in octogenarian patients with
      acute myocardial infarction (AMI) treated by primary angioplasty. We used our
      clinical database consisting of all patients treated using primary angioplasty (<
      or = 12 hours) for acute ST elevation myocardial infarction excluding patients
      with cardiogenic shock. The clinical and angiographic results of non-shock
      patients, distinguished according to age < 80 years and > or = 80 years, was
      characterized by higher 30-day mortality among the elderly compared to younger
      patients (12% versus 3.3%) and overall major cardiac events (17.5% versus 7.4%).
      Thus, primary angioplasty in the octogenarian patients, albeit feasible and
      relatively safe, is associated with 30-days death rates that are higher in
      octogenarian patients as compared to younger patients.

PMID- 16805212
TI  - [Percutaneous carotid artery stenting in high-risk patients].
AB  - Recent studies have shown that percutaneous carotid artery angioplasty and
      stenting can be safely performed in patients with carotid artery stenosis,
      especially those considered to be at high-risk for surgery. AIM: We evaluated the
      safety and feasibility of carotid artery angioplasty and stenting, with and
      without distal protection devices in patients at high-risk for surgical
      endarterectomy. METHODS: A total of 169 consecutive patients underwent 185
      procedures and 189 stents were deployed successfully in 195 lesions. The majority
      of patients (51%) had restenosis after a prior carotid endarterectomy, 40% were
      considered to be ineligible for carotid endarterectomy by both the vascular
      surgeons and the interventional cardiologist and 7% were considered ineligible
      for surgery due to hostile neck anatomy. RESULTS: Distal embolic protection
      devices were used in 52% of all cases. Procedural success was achieved in 181 of
      185 procedures (98%). The overall rate of in-hospital major adverse
      cerebrovascular events (death, major stroke, and myocardial infarction) was 2.4%.
      In-hospital event rates in patients with prior carotid endarterectomy were
      comparable to patients with de novo lesions with 3.3% vs. 1.1% death/ stroke at
      30 days, and 3.3% and 3.3% stroke/death rates at 30 days, respectively. When
      distal protection devices were used death/stroke rates were 0% as compared to
      4.7% when distal protection was not used (p = NS). However, minor embolic
      phenomena were observed in both primary and secondary lesions independent of the
      use of distal protection. CONCLUSIONS: These results support the use of carotid
      artery angioplasty and stenting in high-risk patients with significant primary or
      secondary carotid artery stenosis. In both types of lesions, acceptable results
      justify its use as a valid revascularization method. While clinical embolic
      events occur in a minority of patients in both lesion types, they are not
      entirely prevented by distal protection devices.

PMID- 16805213
TI  - [Intravenous flecainide administration for conversion of paroxysmal atrial
      fibrillation in the emergency room].
AB  - INTRODUCTION: Since the removal of intravenous propafenone from the Israeli
      market, flecainide is the only intravenous antiarrhythmic class 1C drug available
      nowadays in Israel. AIM: The study aimed to report our experience of intravenous
      flecainide administration in the treatment of paroxysmal atrial fibrillation
      (PAF) in the Emergency Room (ER). METHODS: Patients with AF lasting > 1 hour and
      <48 hour duration were considered possible candidates for entry into the study.
      Exclusion criteria were clinical signs of congestive heart failure, acute
      coronary syndrome, electrolyte imbalances, significant hepatic and renal disease,
      and any previously documented conduction disturbance. Flecainide was administered
      as a bolus dose of 2mg/kg in 10 minutes (maximum 150 mg). The patients with a
      ventricular response > 130 beats/min received intravenous verapamil or metoprolol
      in order to reduce the ventricular rate. Efficacy was defined as conversion to
      sinus rhythm (SR) within 120 minutes of starting medication. RESULTS: Twenty
      three consecutive patients were enrolled in the study. Their mean age was 60 +/-
      19 years; the mean ventricular response at admission was 128 +/- 26 beats/min. SR
      was achieved in 10 patients (43%) after the intravenous bolus of flecainide (10
      minutes) and in 17 patients (74%) 120 minutes after the beginning of the therapy.
      COMPLICATIONS: Hypotension (systolic blood pressure < 90 mmHg) was reported in 1
      patient and QRS enlargement was seen in 1 patient. CONCLUSION: Intravenous
      flecainide has effective and rapid action in the conversion of PAF and its
      administration is safe in the treatment of this arrhythmia in the ER.

PMID- 16805214
TI  - [Brugada syndrome--unique ECG pattern].
AB  - In 1992, the Brugada brothers, cardiologists from Spain, described 8 patients who
      survived sudden cardiac death and had a unique ECG pattern.
      Electrocardiographically characterized by a distinct ST-segment elevation in the
      right precordial leads. The syndrome is associated with a high risk for sudden
      cardiac death in young and otherwise healthy adults. Since then, thousands of
      cases were published. The syndrome is still under-diagnosed which has a serious
      implication on patient's prognosis. We described one patient who was misdiagnosed
      at the ER.

PMID- 16805215
TI  - [Patients with recurrent malignant ventricular arrhythmias--therapeutic
      challenge].
AB  - Patients with malignant refractory ventricular arrhythmias present a unique
      therapeutic challenge. In recent years, this challenge has become even more
      complex due to the wide spread use of implantable cardiac defibrillators. If, in
      the past, a majority of the patients succumbed due to these arrhythmias, today,
      due to the defibrillators, they survive and then need further treatment. The
      defibrillators treat the arrhythmias when they occur but in most cases do not
      prevent their initiation. In many cases we need to resort to other modalities. We
      present three patients who exemplify various options of dealing with this complex
      issue.

PMID- 16805216
TI  - [Heart to heart: rehabilitation of sexuality in cardiac patients].
AB  - Heart disease in general and acute myocardial infarction involve sexual
      dysfunction caused by anxiety and by the same physiological problems that caused
      the heart problem, namely endothelial dysfunction. Unfortunately, many patients
      and their spouses hesitate to approach their doctor on issues related to their
      sexual concerns. Furthermore, the medical team in general and doctors in
      particular are irresolute in bringing up sexual issues when dealing with overall
      cardiac rehabilitation. Although patients can safely resume sexual activity at
      some point, only one in four actually return to their previous level of sexual
      activity. If we really want to assist in the rehabilitation of patients we have
      to advise them about resuming their sex life. Solving sexual problems can serve
      as a tool in primary, secondary and tertiary prevention of cardiac problems, as
      it can be used as an "arm swinger" for changing one's life habits. We urge
      increased research and treatment of sexual problems, in cardiac patients in
      general and in female patients in particular.

PMID- 16805217
TI  - [Surgical ventricular restoration--new horizons in the treatment of ischemic
      cardiomyopathy].
AB  - Heart failure is a major health problem with increasing prevalence due to aging
      of the population and in addition to an increase in effective treatment and early
      myocardial reperfusion during acute myocardial infarction. Postinfarction left
      ventricular remodeling is characterized by chamber dilatation with an abnormal
      spherical shape leading to systolic and diastolic dysfunction frequently
      associated with mitral valve insufficiency and eventually heart failure.
      Intensive medical management reduces symptoms and improves survival. However,
      patients who are in NYHA functional class III or IV still have a poor prognosis.
      In this review article we will endeavor to summarize the emerging surgical
      approach "surgical ventricular restoration" for treating ventricular remodeling
      and ischemic cardiomyopathy. These concepts of restoration of the elliptical
      shape of the left ventricle and re-establishing the normal structure of the sub
      valvular mitral apparatus are performed recently in our department.

PMID- 16805218
TI  - [Endothelial progenitor cells and atherosclerosis].
AB  - The integrity and functional activity of the endothelial monolayer play a crucial
      role in the prevention of atherosclerosis. Extended endothelial cell damage by
      cardiovascular risk factors can result in endothelial cell apoptosis with loss of
      the integrity of the endothelium. Endothelial progenitor cells (EPCs) originating
      from the bone marrow play a significant role in neovascularization of ischemic
      tissues and in re-endothelialization of injured blood vessels. This may
      potentially limit atherosclerotic lesion formation. However, risk factors for
      coronary artery disease such as age and smoking, hypertension, hyperlipidemia and
      diabetes reduce the number and functional activity of these circulating
      endothelial progenitor cells, potentially restricting the therapeutic prospective
      of progenitor cells and limiting the regenerative capacity. The impairment of
      EPCs by risk factors may contribute to atherogenesis and atherosclerotic disease
      progression. The article reviews the role of EPCs as markers for atherosclerosis
      and cardiovascular outcomes and highlights possible novel strategies to interfere
      with the balance of injury and repair mechanisms.

PMID- 16805219
TI  - [Endothelial progenitor cells (EPCs)--new tools for diagnosis and therapy].
AB  - Accumulating evidence suggests that postnatal bone marrow is a source of cells
      that can participate in postnatal neovascularization and vascular homeostasis.
      Among these cells, a scarce population of endothelial progenitor cells (EPCs)
      have the capacity to migrate to the peripheral circulation, proliferate and
      differentiate into mature endothelial cells in response to stimulating signals
      emanating from vascular injuries or during tumor growth. Questions persist,
      however, regarding the precise panel of cell surface markers that defined EPCs,
      as well as the different mechanisms stimulating or inhibiting their mobilization
      and differentiation. In the last decade, EPCs number and function have been
      correlated with risk factors for cardiovascular and peripheral vascular diseases.
      The authors review experimental results obtained from both animal studies and
      recent clinical trials, which point to the importance of EPCs potential as
      diagnostic markers and therapeutic tools in ischemic diseases. Furthermore, the
      article discusses the risk of potentially harmful side effects of altered EPCs
      number and functional properties, a critical barrier to overcome while bringing
      progenitor cell therapy to the clinical arena.

PMID- 16805220
TI  - [ST myocardial infarction with spontaneous coronary reperfusion].
AB  - ST elevation myocardial infarction continues to be a major medical problem even
      in the beginning of the 21st century. Treatment guidelines for these patients are
      based on multiple randomized clinical trials. In order to minimize myocardial
      damage, early patency of the infarct relating artery must be accomplished. This
      is the major difference in the treatment strategy between ST elevation myocardial
      infarction and other acute coronary syndromes. Primary percutaneous coronary
      intervention and fibrinolysis are the two treatment modalities for achieving
      myocardial reperfusion. The subgroup of ST elevation myocardial infarction with
      spontaneous coronary artery reperfusion carries a more favorable prognosis. This
      review addresses the clinical characteristics, natural history, prognosis and
      treatment strategies for this group, with special emphasis on the optimal timing
      for revascularization, and the role of glycoprotein IIb/IIIa inhibitors.

PMID- 16805221
TI  - [Current perspectives on emergent coronary angioplasty for acute ST-elevation
      myocardial infarction].
AB  - In recent years, emergent catheter-based angioplasty has become the preferred
      treatment for acute ST-elevation myocardial infarction. The use of balloon
      angioplasty, stents and recently introduced drug eluting stents allowed optimized
      and sustained coronary patency. However, it became apparent that epicardial
      patency would not guarantee optimized myocardial tissue perfusion. Therefore,
      additional work is required to preserve the damaged tissue afflicted by
      myocardial infarction. There is also a need for more research directed towards
      improved prognosis and myocardial preservation.

PMID- 16805222
TI  - [Automatic external defibrillator (AED) and public access defibrillation (PAD)].
AB  - Sudden death is a major public hazard and is usually caused by ventricular
      fibrillation (VF). Although in the majority of cases witnesses are to be found,
      resuscitation efforts are begun only in a minority of victims. The only treatment
      for VF is electrical shock and the time from collapse to resuscitation and
      defibrillation determine prognosis. Automated external defibrillator (AED) is a
      new device capable of effectively identifying and treating VF. It is unique in
      the sense that it can be operated by a non-medical operator following short
      training. Recent evidence of the survival benefit of AED utility is emerging.
      During the coming years, AEDs will be introduced to a growing number of hospitals
      and public places. This review summarizes the rationale for use, advantages, and
      disadvantages as well as the current status of AEDs and recommendations for
      placement of AEDs in Israel.

PMID- 16805223
TI  - [Erythropoietin as a protective agent in myocardial ischemia].
AB  - Erythropoietin and its receptor, a cytokine hormone long-known for its pro
      erythropoietic effect, has been found to be expressed on a variety of tissues,
      including the cardiovascular system. Recent experimental studies in the ischemia
      reperfusion model have demonstrated that erythropoietin has a significant
      cardioprotective and pro-angiogenic effect. This effect is quantified by a
      reduction in the relative infarct and apoptosis area and improved recovery of
      mechanical function. Despite potentially detrimental effects, erythropoietin has
      been used extensively in the last decade for treatment of anemia associated with
      chronic renal failure, and it has been found to be a safe drug in humans. The
      potential role of erythropoietin in the treatment of ischemic heart disease in
      humans has yet to be demonstrated in preliminary clinical trials.

PMID- 16805224
TI  - Vaccines and vaccination programs revisited.

PMID- 16805225
TI  - The return of pertussis: who is responsible? What can be done?
AB  - The Israel Ministry of Health's epidemiology department reported a record number
      of 1564 new pertussis cases in 2004. This brings the incidence rate to 23 per
      100,000 population, indicating a marked increase in the prevalence of pertussis,
      from 1-3/100,000 in 1998, 9 in 2001, to 14 in 2003. The rate of atypical
      pertussis presentations in vaccinated patients, the decline in pertussis immunity
      post-vaccination, and the decreased awareness of potential infections in the
      adult population make the diagnosis of pertussis difficult and contribute to the
      rising incidence. In this article we review the current literature in order to
      increase awareness of the occurrence of pertussis in children as well as adults,
      discuss the laboratory diagnostic methods being used, and report the currently
      recommended means of treating the disease.

PMID- 16805226
TI  - The re-emergence of pertussis in Israel.
AB  - BACKGROUND: Pertussis is the only vaccine-preventable disease that has re-emerged
      in Israel. The reported crude incidence of the disease increased 16-fold since
      1998. OBJECTIVES: To describe the epidemiology of pertussis and explain the
      substantial increase in reported pertussis incidence in Israel in recent years.
      METHODS: Crude and specific pertussis incidence by age, patient immunization
      status, hospitalization rate, and national immunization coverage rate were
      calculated from information provided by the public health offices of the Ministry
      of Health. RESULTS: The reported crude incidence of pertussis increased from 1
      2/100,000 in 1994-98 to 23/100,000 in 2004. The trend was observed in all age
      groups, being most prominent in infants under age 1 year and in children aged 5
      14. The incidence of pertussis was substantially higher in unvaccinated and
      partly vaccinated compared to fully vaccinated persons. Fifteen percent of
      notified cases were hospitalized, but in infants under age 1 year the
      hospitalization rate was 50%. National pertussis immunization coverage by age 2
      years was stable during the last 10 years. CONCLUSIONS: There are several
      possible explanations for the re-emergence of pertussis in Israel. The most
      plausible reason seems to be the waning of vaccine-induced immunity in face of
      infrequent natural exposure to the infectious agent and lack of a pertussis
      vaccine booster dose after age 1.

PMID- 16805227
TI  - Oral poliovaccine: will it help eradicate polio or cause the next epidemic?
AB  - BACKGROUND: Poliovirus rapidly evolves by nucleic acid substitutions and genetic
      recombination with other polioviruses and non-polio enteroviruses. Evolving oral
      poliovaccine can rapidly revert to neurovirulence and undergo antigenic
      alterations. OBJECTIVES: To evaluate the threat of vaccine-derived poliovirus (1
      15% divergence from the respective Sabin strain) for a poliomyelitis-free
      population in a country with a long-standing routine vaccination program.
      METHODS: We characterized genetic and antigenic changes in OPV (Sabin) strains
      isolated from sewage in Israel and evaluated intestinal immunity by measuring
      fecal excretion after OPV challenge of vaccinated children. RESULTS:
      Characterization of poliovirus from sewage revealed eight type 2 and three type 3
      vaccine polioviruses that had replicated and started to evolve (vaccine that
      replicated and diverged by 0.5 to < or = 1.0%) and nine highly diverged type 2
      vaccine-derived polioviruses (1-15% divergence from the respective Sabin strain)
      with 8-14% divergence between the years 1998 and 2005. Six of the eleven VRPV
      uniquely recombined with OPV and/or NPEV. The nine VDPV were epidemically
      related, genotypically neurovirulent, and had 10-15 amino acid substitutions in
      antigenic sites altering their antigenicity, but shared a single recombination.
      Type 2 OPV was excreted by 23% and 17% of infants challenged with OPV 3 months
      after partial immunization (two doses each of OPV and enhanced inactivated
      poliovirus) or full immunization (three doses of each) respectively, despite high
      humoral antibody titers. CONCLUSIONS: Our findings, which show that OPV is
      excreted for a significant period by children with high humoral immunity,
      emphasize the long-term potential threat from VDPV in highly vaccinated
      populations. An adequate immunization program, combined with environmental
      surveillance, is necessary to prevent poliomyelitis and community transmission of
      poliovirus.

PMID- 16805228
TI  - Flagella as a platform for epitope-based vaccines.

PMID- 16805229
TI  - Recent improvements in polio and pertussis vaccination policy in Israel, 2005.
AB  - For children born after 1 January 2005, use of the Sabin oral polio vaccine in
      combination with the enhanced-potency Salk inactivated polio vaccine as part of
      the routine vaccination schedule was discontinued. The schedule now includes only
      IPV. In September 2005, a fifth dose of pertussis vaccine was added for pupils in
      their second year of elementary school. This article describes the reasons for
      these changes, which have rendered Israel's routine vaccination program one of
      the most effective in the world.

PMID- 16805230
TI  - Immune thrombocytopenic purpura following influenza vaccination.

PMID- 16805231
TI  - Jewish pediatricians in Nazi Germany: victims of persecution.
AB  - The plight and fate of German Jewish pediatricians during the Nazi period in
      Europe has not received much attention, yet the narratives of the victims still
      resonate today and they deserve to be remembered. The stories of two women serve
      as examples of the fateful turns taken by the lives of many German Jewish
      pediatricians between 1933 and 1945. The two women, Dr. Luci Adelsberger and Dr.
      Lilli Jahn, illustrate both the ordeals endured and the disparate ways the Nazi
      policies ultimately spared or ended lives.

PMID- 16805232
TI  - Initial experience with a cardiologist-based chest pain unit in an emergency
      department in Israel.
AB  - BACKGROUND: Emergency room triage of patients presenting with chest pain
      syndromes may be difficult. Under-diagnosis may be dangerous, while over
      diagnosis may be costly. OBJECTIVES: To report our initial experience with an
      emergency room cardiologist-based chest pain unit in Israel. METHODS: During a 5
      week pilot study, we examined resource utilization and ER diagnosis in 124
      patients with chest pain of uncertain etiology or non-high risk acute coronary
      syndrome. First assessment was performed by the ER physicians and was followed by
      a second assessment by the CPU team. Assessment was based on the following
      parameters: medical history and examination, serial electrocardiography,
      hematology, biochemistry and biomarkers for ACS, exercise stress testing and/or
      64-slice multi-detector cardiac computed tomography angiography. Changes in
      decision between initial assessment and final CPU assessment with regard to
      hospitalization and utilization of resources were recorded. RESULTS: All patients
      had at least two cardiac troponin T measurements, 19 underwent EST, 9
      echocardiography and 29 cardiac MDCT. Fourteen patients were referred for early
      cardiac catheterization (same/next day). A specific working diagnosis was reached
      in 71/84 patients hospitalized, including unstable angina in 39 (31%) and non-ST
      elevation myocardial infarction in 12 (10%). Following CPU assessment, 40/124
      patients (32%) were discharged, 49 (39%) were admitted to Internal Medicine and
      35 (28%) to the Cardiology departments. CPU assessment and extended resources
      allowed discharge of 30/101 patients (30%) who were initially identified as
      candidates for hospitalization after ER assessment. Furthermore, 13/23 patients
      (56%) who were candidates for discharge after initial ER assessment were
      eventually hospitalized. Use of non-invasive tests was significantly greater in
      patients discharged from the ER (85% vs. 38% patients hospitalized) (P < 0.0001).
      The mean ER stay tended to be longer (14.9 +/- 8.6 hours vs. 12.9 +/- 11, P = NS)
      for patients discharged. At 30 days follow-up, there were no adverse events
      (myocardial infarction or death) in any of the 40 patients discharged from the ER
      after CPU assessment. One patient returned to the ER because of chest pain and
      was discharged after reassessment. CONCLUSIONS: Our initial experience showed
      that an ER cardiologist-based chest pain unit improved assessment of patients
      presenting to the ER with chest pain, and enhanced appropriate use of diagnostic
      tests prior to a decision regarding admission/discharge from the ER.

PMID- 16805233
TI  - Sexually transmitted diseases among patients with human immunodeficiency virus in
      northern Israel.
AB  - BACKGROUND: The co-morbidity of human immunodeficiency virus and other sexually
      transmitted diseases in Israel has not been established. OBJECTIVES: To compare
      the prevalence of STDs among HIV-positive patients to HIV-negative patients
      visiting an STD clinic in northern Israel. METHODS: Between December 2000 and
      December 2001, 176 HIV-positive individuals (53% males) were screened and
      compared to 200 HIV-seronegative individuals (76% males). Demographics,
      symptomatology and risk factors were obtained via questionnaire. First-void urine
      samples were tested for the detection of Chlamydia trachomatis and Neisseria
      gonorrhoeae. Serum was tested for type-specific herpes simplex virus-2, hepatitis
      B and syphilis. RESULTS: Relative to the seronegative STD patients, HIV-positive
      patients exhibited significantly greater risk-reducing sexual behaviors such as
      consistent condom use [29/86 (33.7%) vs. 16/187 (8.6%), P < 0.001], and
      abstinence in the previous 6 months [43/125 (34%) vs. 7/185 (3.8%), P < 0.001].
      Nevertheless, STD prevalence was higher among HIV-positive than HIV-negative
      patients (79.5% vs 37.5%, P < 0.001). HSV-2, syphilis and HBV were more common
      among HIV-positive than HIV-negative patients [120/175 (68.8%)] vs. 18/200 (9%),
      P < 0.001)], [43/161 (26.7%) vs. 0%, P < 0.001)], [13/171 (7.6%) vs. 3/200
      (1.5%), P < 0.01)], respectively. In contrast, Chlamydia and gonorrhea were more
      common in HIV-negative patients than HIV-positive patients [3/176 (1.7%)
      vs.13/200 (6.5%), P < 0.05] vs. [0% vs.5/200 (2.5%), P < 0.05], respectively.
      CONCLUSION: Despite the low risk sexual behavior of Israeli HIV patients, they
      had a high prevalence of chronic STDs (e.g., HSV-2, HBV and syphilis). The lower
      prevalence of Chlamydia and gonorrhea among HIV-immunosuppressed patients may be
      attributed to routine antibiotic prophylaxis against opportunistic infections.
      Nevertheless, as advocated by international health organizations, it appears
      prudent to recommend the routine screening of these asymptomatic HIV-positive
      patients for STD pathogens.

PMID- 16805234
TI  - Acute Q fever in Israel: clinical and laboratory study of 100 hospitalized
      patients.
AB  - BACKGROUND: Q fever is endemic in Israel, yet a large series describing the
      clinical spectrum of inpatients with acute Q fever in Israel is lacking.
      OBJECTIVES: To report on the clinical characteristics and outcome of hospitalized
      patients with acute Q fever in Israel. METHODS: We conducted a retrospective
      study of 100 patients hospitalized in six medical centers, in whom acute Q fever
      was diagnosed by the presence of immunoglobulin G and M antibodies to phase II
      Coxiella burnetti antigens. RESULTS: The mean age of the patients was 42.7 +/-
      17.3 years with a male to female ratio of 1.6:1. Acute Q fever occurred
      throughout the year but was more common during the warm season. The most common
      clinical presentation was acute febrile disease (98%, mean length of fever 15.5
      +/- 8.6 days), followed by hepatitis (67%) and pneumonia (32%). The prominent
      laboratory findings included: accelerated erythrocyte sedimentation rate, normal
      or low white blood count with many band forms, thrombocytopenia, and abnormal
      urinalysis. Although the diagnosis of acute Q fever was not known during the
      hospitalization in the majority of patients, about 80% of our patients received
      appropriate antibiotic therapy and all patients recovered. CONCLUSIONS: Patients
      with acute Q fever present with a typical clinical picture that enables clinical
      diagnosis and empiric therapy in most cases. The prognosis of hospitalized
      patients with acute Q fever is excellent.

PMID- 16805235
TI  - Preoperative clinical, mammographic and sonographic assessment of neoadjuvant
      chemotherapy response in breast cancer.
AB  - BACKGROUND: The current methods for pre- and post-chemotherapy examination of the
      extent of disease in the breast and lymph nodes do not provide sufficiently
      accurate information and, not infrequently, the surgeon has to re-operate.
      OBJECTIVES: To correlate the findings between three methods of examination
      (physical examination, ultrasonography, mammography), all performed by the same
      oncologic and radiologic team, in patients with locally advanced breast cancer or
      a tumor/breast tissue ratio that precludes breast-conserving surgery. METHODS:
      Forty patients (median age 48 years, range 24-73) with locally advanced breast
      cancer or with a tumor/breast ratio that precluded breast-conserving surgery were
      evaluated by the same medical team and received neoadjuvant chemotherapy. Surgery
      was performed in all, and the pathologic specimen was correlated with the results
      of the other examinations. RESULTS: In the pre-chemotherapy evaluation, the
      imaging findings of the breast correlated with the physical findings in 78% of
      the patients and with the axilla examination in 66.7%. In the post-chemotherapy
      analysis, imaging agreed with the physical findings of the breast in 62.2% and in
      76.3% of the axilla. Sonography best detected occult breast disease and axillary
      lymph nodes but correlated with pathology in only 58% of the patients in
      diagnosing breast tumor and in 65.8% in diagnosing axillary lymph nodes.
      Mammography correlated with breast and lymph node pathology in half the patients.
      CONCLUSIONS: None of the classical methods of post-neoadjuvant chemotherapy
      evaluations could adequately delineate the actual extent of the disease in the
      breast and axillary lymph nodes. More exacting techniques of imaging combined
      with the classical methods are required.

PMID- 16805236
TI  - Prenatal panel screening considerations for non-neuronopathic Gaucher disease in
      the Ashkenazi-Jewish population.
AB  - The Ashkenazi-Jewish population is at increased risk for several recessively
      inherited disorders. While some of the disorders have severe or fatal symptom
      manifestations, others, such as non-neuronopathic Gaucher disease, do not usually
      pose a serious, life-threatening illness. Many healthcare centers in Israel offer
      prenatal panel screening. Controversy exists over the inclusion of Gaucher
      disease in the panel screening, especially since Gaucher disease screening lacks
      prognostic reliability. Most screening participants do not discriminate between
      the specific tests in the panel and are unable to discern between severe, life
      threatening diseases and those that are less severe and even treatable. By
      including screening for Gaucher in the panel screening program, there is risk of
      a "panel effect," leading to termination of a pregnancy positive for Gaucher
      disease, without sufficient knowledge and understanding of the disease.
      Increasing medical and public awareness and knowledge of the disease, its
      prognosis and treatment options may reduce the rate of under-informed abortions
      associated with prenatal screening for Gaucher disease.

PMID- 16805237
TI  - Chest pain unit in Israel: are we on the road?

PMID- 16805238
TI  - Diagnosing, preventing and managing sexually transmitted diseases in persons
      living with HIV/AIDS.

PMID- 16805239
TI  - Paradoxical transtentorial herniation in a patient with pseudotumor cerebri.

PMID- 16805240
TI  - Cardiac murmur detected by the patient or a person nearby: an auditory finding
      indicating the need for surgical intervention.

PMID- 16805241
TI  - Small bowel obstruction by a carcinoid tumor in a patient with familial
      Mediterranean fever.

PMID- 16805242
TI  - Close look at ECG tracing after termination of supraventricular tachycardia with
      adenosine.

PMID- 16805243
TI  - Severe anemia diagnosed on computed tomography.

PMID- 16805244
TI  - Infant botulism.

PMID- 16805245
TI  - The flora of the umbilicus as source of surgical wound infection.

PMID- 16805246
TI  - [Excluded patient group. A new approach is necessary for adults with
      ADHD/Tourette syndrome/autism spectrum disorders].

PMID- 16805247
TI  - [Adults with neuropsychiatric diagnosis are not receiving sufficient help. A
      survey shows extensive needs of treatment and support].

PMID- 16805248
TI  - [Celiac disease as a model for autoimmune disease. Transglutaminase has the key
      role--stress reaction triggers the vicious circle].

PMID- 16805250
TI  - [Recognize ADHD as dual diagnosis!].

PMID- 16805249
TI  - [HIV concerns everyone].

PMID- 16805251
TI  - [Good evidence for benefits of cholinesterase inhibitors in Parkinson dementia is
      still missing].

PMID- 16805252
TI  - [Late start for Swedish anesthesiology. Development of anesthesiology in Sweden
      1904-1942 reflected in Lakartidningen].

PMID- 16805253
TI  - Views on visualization.
AB  - The field of visualization is maturing. Many problems have been solved and new
      directions are sought. In order to make good choices, an understanding of the
      purpose and meaning of visualization is needed. In this paper, visualization is
      considered from multiple points of view. First, a technological viewpoint is
      adopted, where the value of visualization is measured based on effectiveness and
      efficiency. An economic model of visualization is presented and benefits and
      costs are established. Next, consequences and limitations of visualization are
      discussed (including the use of alternative methods, high initial costs,
      subjectiveness, and the role of interaction). Example uses of the model for the
      judgment of existing classes of methods are given to understand why they are or
      are not used in practice. However, such an economic view is too restrictive.
      Alternative views on visualization are presented and discussed: visualization as
      an art, visualization as design and, finally, visualization as a scientific
      discipline.

PMID- 16805254
TI  - HDR VolVis: high dynamic range volume visualization.
AB  - In this paper, we present an interactive high dynamic range volume visualization
      framework (HDR VolVis) for visualizing volumetric data with both high spatial and
      intensity resolutions. Volumes with high dynamic range values require high
      precision computing during the rendering process to preserve data precision.
      Furthermore, it is desirable to render high resolution volumes with low opacity
      values to reveal detailed internal structures, which also requires high precision
      compositing. High precision rendering will result in a high precision
      intermediate image (also known as high dynamic range image). Simply rounding up
      pixel values to regular display scales will result in loss of computed details.
      Our method performs high precision compositing followed by dynamic tone mapping
      to preserve details on regular display devices. Rendering high precision volume
      data requires corresponding resolution in the transfer function. To assist the
      users in designing a high resolution transfer function on a limited resolution
      display device, we propose a novel transfer function specification interface with
      nonlinear magnification of the density range and logarithmic scaling of the
      color/ opacity range. By leveraging modern commodity graphics hardware,
      multiresolution rendering techniques and out-of-core acceleration, our system can
      effectively produce an interactive visualization of large volume data, such as
      2,048(3).

PMID- 16805255
TI  - Methods and framework for visualizing higher-order finite elements.
AB  - The finite element method is an important, widely used numerical technique for
      solving partial differential equations. This technique utilizes basis functions
      for approximating the geometry and the variation of the solution field over
      finite regions, or elements, of the domain. These basis functions are generally
      formed by combinations of polynomials. In the past, the polynomial order of the
      basis has been low-typically of linear and quadratic order. However, in recent
      years so-called p and hp methods have been developed, which may elevate the order
      of the basis to arbitrary levels with the aim of accelerating the convergence of
      the numerical solution. The increasing complexity of numerical basis functions
      poses a significant challenge to visualization systems. In the past, such systems
      have been loosely coupled to simulation packages, exchanging data via file
      transfer, and internally reimplementing the basis functions in order to perform
      interpolation and implement visualization algorithms. However, as the basis
      functions become more complex and, in some cases, proprietary in nature, it
      becomes increasingly difficult if not impossible to reimplement them within the
      visualization system. Further, most visualization systems typically process
      linear primitives, in part to take advantage of graphics hardware and, in part,
      due to the inherent simplicity of the resulting algorithms. Thus, visualization
      of higher-order finite elements requires tessellating the basis to produce data
      compatible with existing visualization systems. In this paper, we describe
      adaptive methods that automatically tessellate complex finite element basis
      functions using a flexible and extensible software framework. These methods
      employ a recursive, edge-based subdivision algorithm driven by a set of error
      metrics including geometric error, solution error, and error in image space.
      Further, we describe advanced pretessellation techniques that guarantees capture
      of the critical points of the polynomial basis. The framework has been designed
      using the adaptor design pattern, meaning that the visualization system need not
      reimplement basis functions, rather it communicates with the simulation package
      via simple programmatic queries. We demonstrate our method on several examples,
      and have implemented the framework in the open-source visualization system VTK.

PMID- 16805256
TI  - Projected tetrahedra revisited: a barycentric formulation applied to digital
      radiograph reconstruction using higher-order attenuation functions.
AB  - This paper presents a novel method for volume rendering of unstructured grids.
      Previously, we introduced an algorithm for perspective-correct interpolation of
      barycentric coordinates and computing polynomial attenuation integrals for a
      projected tetrahedron using graphics hardware. Here, we enhance the algorithm by
      providing a simple and efficient method to compute the projected shape
      (silhouette) and tessellation of a tetrahedron, in perspective and orthographic
      projection models. Our tessellation algorithm is published here for the first
      time. Compared with works of other groups on rendering unstructured grids, the
      main contributions of this work are: 1) A new algorithm for finding the
      silhouette of a projected tetrahedron. 2) A method for interpolating barycentric
      coordinates and thickness on the faces of the tetrahedron. 3) Visualizing higher
      order attenuation functions using GPU without preintegration. 4) Capability of
      applying shape deformations to a rendered tetrahedral mesh without significant
      performance loss. Our visualization model is independent of depth-sorting of the
      cells. We present imaging and timing results of our implementation, and an
      application in time-critical "2D-3D" deformable registration of anatomical
      models. We discuss the impact of using higher-order functions on quality and
      performance.

PMID- 16805257
TI  - A topological approach to simplification of three-dimensional scalar functions.
AB  - This paper describes an efficient combinatorial method for simplification of
      topological features in a 3D scalar function. The Morse-Smale complex, which
      provides a succinct representation of a function's associated gradient flow
      field, is used to identify topological features and their significance. The
      simplification process, guided by the Morse-Smale complex, proceeds by repeatedly
      applying two atomic operations that each remove a pair of critical points from
      the complex. Efficient storage of the complex results in execution of these
      atomic operations at interactive rates. Visualization of the simplified complex
      shows that the simplification preserves significant topological features while
      removing small features and noise.

PMID- 16805258
TI  - Visualization of Seifert surfaces.
AB  - The genus of a knot or link can be defined via Seifert surfaces. A Seifert
      surface of a knot or link is an oriented surface whose boundary coincides with
      that knot or link. Schematic images of these surfaces are shown in every text
      book on knot theory, but from these it is hard to understand their shape and
      structure. In this paper, the visualization of such surfaces is discussed. A
      method is presented to produce different styles of surface for knots and links,
      starting from the so-called braid representation. Application of Seifert's
      algorithm leads to depictions that show the structure of the knot and the
      surface, while successive relaxation via a physically based model gives shapes
      that are natural and resemble the familiar representations of knots. Also, we
      present how to generate closed oriented surfaces in which the knot is embedded,
      such that the knot subdivides the surface into two parts. These closed surfaces
      provide a direct visualization of the genus of a knot. All methods have been
      integrated in a freely available tool, called SeifertView, which can be used for
      educational and presentation purposes.

PMID- 16805259
TI  - Visual analysis of gel-free proteome data.
AB  - We present a visual exploration system supporting protein analysis when using gel
      free data acquisition methods. The data to be analyzed is obtained by coupling
      liquid chromatography (LC) with mass spectrometry (MS). LC-MS data have the
      properties of being nonequidistantly distributed in the time dimension (measured
      by LC) and being scattered in the mass-to-charge ratio dimension (measured by
      MS). We describe a hierarchical data representation and visualization method for
      large LC-MS data. Based on this visualization, we have developed a tool that
      supports various data analysis steps. Our visual tool provides a global
      understanding of the data, intuitive detection and classification of experimental
      errors, and extensions to LC-MS/MS, LC/LC-MS, and LC/LC-MS/MS data analysis. Due
      to the presence of randomly occurring rare isotopes within the same protein
      molecule, several intensity peaks may be detected that all refer to the same
      peptide. We have developed methods to unite such intensity peaks. This
      deisotoping step is visually documented by our system, such that
      misclassification can be detected intuitively. For differential protein
      expression analysis, we compute and visualize the differences in protein amounts
      between experiments. In order to compute the differential expression, the
      experimental data need to be registered. For registration, we perform a nonrigid
      warping step based on landmarks. The landmarks can be assigned automatically
      using protein identification methods. We evaluate our methods by comparing
      protein analysis with and without our interactive visualization-based exploration
      tool.

PMID- 16805260
TI  - An approach to the perceptual optimization of complex visualizations.
AB  - This paper proposes a new experimental framework within which evidence regarding
      the perceptual characteristics of a visualization method can be collected, and
      describes how this evidence can be explored to discover principles and insights
      to guide the design of perceptually near-optimal visualizations. We make the case
      that each of the current approaches for evaluating visualizations is limited in
      what it can tell us about optimal tuning and visual design. We go on to argue
      that our new approach is better suited to optimizing the kinds of complex visual
      displays that are commonly created in visualization. Our method uses human-in-the
      loop experiments to selectively search through the parameter space of a
      visualization method, generating large databases of rated visualization
      solutions. Data mining is then used to extract results from the database, ranging
      from highly specific exemplar visualizations for a particular data set, to more
      broadly applicable guidelines for visualization design. We illustrate our
      approach using a recent study of optimal texturing for layered surfaces viewed in
      stereo and in motion. We show that a genetic algorithm is a valuable way of
      guiding the human-in-the-loop search through visualization parameter space. We
      also demonstrate several useful data mining methods including clustering,
      principal component analysis, neural networks, and statistical comparisons of
      functions of parameters.

PMID- 16805261
TI  - Explanatory and illustrative visualization of special and general relativity.
AB  - This paper describes methods for explanatory and illustrative visualizations used
      to communicate aspects of Einstein's theories of special and general relativity,
      their geometric structure, and of the related fields of cosmology and
      astrophysics. Our illustrations target a general audience of laypersons
      interested in relativity. We discuss visualization strategies, motivated by
      physics education and the didactics of mathematics, and describe what kind of
      visualization methods have proven to be useful for different types of media, such
      as still images in popular science magazines, film contributions to TV shows,
      oral presentations, or interactive museum installations. Our primary approach is
      to adopt an egocentric point of view: The recipients of a visualization
      participate in a visually enriched thought experiment that allows them to
      experience or explore a relativistic scenario. In addition, we often combine
      egocentric visualizations with more abstract illustrations based on an outside
      view in order to provide several presentations of the same phenomenon. Although
      our visualization tools often build upon existing methods and implementations,
      the underlying techniques have been improved by several novel technical
      contributions like image-based special relativistic rendering on GPUs, special
      relativistic 4D ray tracing for accelerating scene objects, an extension of
      general relativistic ray tracing to manifolds described by multiple charts, GPU
      based interactive visualization of gravitational light deflection, as well as
      planetary terrain rendering. The usefulness and effectiveness of our
      visualizations are demonstrated by reporting on experiences with, and feedback
      from, recipients of visualizations and collaborators.

PMID- 16805262
TI  - Drawing directed graphs using quadratic programming.
AB  - We describe a new method for visualization of directed graphs. The method
      combines constraint programming techniques with a high performance force-directed
      placement (FDP) algorithm. The resulting placements highlight hierarchy in
      directed graphs while retaining useful properties of FDP; such as emphasis of
      symmetries and preservation of proximity relations. Our algorithm automatically
      identifies those parts of the digraph that contain hierarchical information and
      draws them accordingly. Additionally, those parts that do not contain hierarchy
      are drawn at the same quality expected from a nonhierarchical, undirected layout
      algorithm. Our experiments show that this new approach is better able to convey
      the structure of large digraphs than the most widely used hierarchical graph
      drawing method. An interesting application of our algorithm is directional
      multidimensional scaling (DMDS). DMDS deals with low-dimensional embedding of
      multivariate data where we want to emphasize the overall flow in the data (e.g.,
      chronological progress) along one of the axes.

PMID- 16805263
TI  - Designing for social data analysis.
AB  - The NameVoyager, a Web-based visualization of historical trends in baby naming,
      has proven remarkably popular. We describe design decisions behind the
      application and lessons learned in creating an application that makes do-it
      yourself data mining popular. The prime lesson, it is hypothesized, is that an
      information visualization tool may be fruitfully viewed not as a tool but as part
      of an online social environment. In other words, to design a successful
      exploratory data analysis tool, one good strategy is to create a system that
      enables "social" data analysis. We end by discussing the design of an extension
      of the NameVoyager to a more complex data set, in which the principles of social
      data analysis played a guiding role.

PMID- 16805264
TI  - Parallel sets: interactive exploration and visual analysis of categorical data.
AB  - Categorical data dimensions appear in many real-world data sets, but few
      visualization methods exist that properly deal with them. Parallel Sets are a new
      method for the visualization and interactive exploration of categorical data that
      shows data frequencies instead of the individual data points. The method is based
      on the axis layout of parallel coordinates, with boxes representing the
      categories and parallelograms between the axes showing the relations between
      categories. In addition to the visual representation, we designed a rich set of
      interactions. Parallel Sets allow the user to interactively remap the data to new
      categorizations and, thus, to consider more data dimensions during exploration
      and analysis than usually possible. At the same time, a metalevel, semantic
      representation of the data is built. Common procedures, like building the cross
      product of two or more dimensions, can be performed automatically, thus
      complementing the interactive visualization. We demonstrate Parallel Sets by
      analyzing a large CRM data set, as well as investigating housing data from two US
      states.

PMID- 16805265
TI  - Registration using natural features for augmented reality systems.
AB  - Registration is one of the most difficult problems in augmented reality (AR)
      systems. In this paper, a simple registration method using natural features based
      on the projective reconstruction technique is proposed. This method consists of
      two steps: embedding and rendering. Embedding involves specifying four points to
      build the world coordinate system on which a virtual object will be superimposed.
      In rendering, the Kanade-Lucas-Tomasi (KLT) feature tracker is used to track the
      natural feature correspondences in the live video. The natural features that have
      been tracked are used to estimate the corresponding projective matrix in the
      image sequence. Next, the projective reconstruction technique is used to transfer
      the four specified points to compute the registration matrix for augmentation.
      This paper also proposes a robust method for estimating the projective matrix,
      where the natural features that have been tracked are normalized (translation and
      scaling) and used as the input data. The estimated projective matrix will be used
      as an initial estimate for a nonlinear optimization method that minimizes the
      actual residual errors based on the Levenberg-Marquardt (LM) minimization method,
      thus making the results more robust and stable. The proposed registration method
      has three major advantages: 1) It is simple, as no predefined fiducials or
      markers are used for registration for either indoor and outdoor AR applications.
      2) It is robust, because it remains effective as long as at least six natural
      features are tracked during the entire augmentation, and the existence of the
      corresponding projective matrices in the live video is guaranteed. Meanwhile, the
      robust method to estimate the projective matrix can obtain stable results even
      when there are some outliers during the tracking process. 3) Virtual objects can
      still be superimposed on the specified areas, even if some parts of the areas are
      occluded during the entire process. Some indoor and outdoor experiments have been
      conducted to validate the performance of this proposed method.

PMID- 16805266
TI  - 3D distance fields: a survey of techniques and applications.
AB  - A distance field is a representation where, at each point within the field, we
      know the distance from that point to the closest point on any object within the
      domain. In addition to distance, other properties may be derived from the
      distance field, such as the direction to the surface, and when the distance field
      is signed, we may also determine if the point is internal or external to objects
      within the domain. The distance field has been found to be a useful construction
      within the areas of computer vision, physics, and computer graphics. This paper
      serves as an exposition of methods for the production of distance fields, and a
      review of alternative representations and applications of distance fields. In the
      course of this paper, we present various methods from all three of the above
      areas, and we answer pertinent questions such as How accurate are these methods
      compared to each other? How simple are they to implement?, and What is the
      complexity and runtime of such methods?

PMID- 16805267
TI  - Digital marbling: a multiscale fluid model.
AB  - This paper presents a multiscale fluid model based on mesoscale dynamics and
      viscous fluid equations as a generic tool for digital marbling purposes. The
      model uses an averaging technique on the adaptation of a stochastic mesoscale
      model to obtain the effect of fluctuations at different levels. It allows various
      user controls to simulate complex flow behaviors as in traditional marbling
      techniques, as well as laminar and turbulent flows. Material transport is based
      on an improved advection solution to be able to match the highly detailed, sharp
      fluid interfaces in marbling patterns. In the transport model, two reaction
      models are introduced to create different effects and to simulate density
      fluctuations.

PMID- 16805268
TI  - Real-time markerless tracking for augmented reality: the virtual visual servoing
      framework.
AB  - Tracking is a very important research subject in a real-time augmented reality
      context. The main requirements for trackers are high accuracy and little latency
      at a reasonable cost. In order to address these issues, a real-time, robust, and
      efficient 3D model-based tracking algorithm is proposed for a "video see through"
      monocular vision system. The tracking of objects in the scene amounts to
      calculating the pose between the camera and the objects. Virtual objects can then
      be projected into the scene using the pose. Here, nonlinear pose estimation is
      formulated by means of a virtual visual servoing approach. In this context, the
      derivation of point-to-curves interaction matrices are given for different 3D
      geometrical primitives including straight lines, circles, cylinders, and spheres.
      A local moving edges tracker is used in order to provide real-time tracking of
      points normal to the object contours. Robustness is obtained by integrating an M
      estimator into the visual control law via an iteratively reweighted least squares
      implementation. This approach is then extended to address the 3D model-free
      augmented reality problem. The method presented in this paper has been validated
      on several complex image sequences including outdoor environments. Results show
      the method to be robust to occlusion, changes in illumination, and mistracking.

PMID- 16805269
TI  - Bilateral recovering of sharp edges on feature-insensitive sampled meshes.
AB  - A variety of computer graphics applications sample surfaces of 3D shapes in a
      regular grid without making the sampling rate adaptive to the surface curvature
      or sharp features. Triangular meshes that interpolate or approximate these
      samples usually exhibit relatively big error around the insensitive sampled sharp
      features. This paper presents a robust general approach conducting bilateral
      filters to recover sharp edges on such insensitive sampled triangular meshes.
      Motivated by the impressive results of bilateral filtering for mesh smoothing and
      denoising, we adopt it to govern the sharpening of triangular meshes. After
      recognizing the regions that embed sharp features, we recover the sharpness
      geometry through bilateral filtering, followed by iteratively modifying the given
      mesh's connectivity to form singlewide sharp edges that can be easily detected by
      their dihedral angles. We show that the proposed method can robustly reconstruct
      sharp edges on feature-insensitive sampled meshes.

PMID- 16805270
TI  - An improved vertex caching scheme for 3D mesh rendering.
AB  - Modern graphics cards are equipped with a vertex cache to reduce the amount of
      data needing to be transmitted to the graphics pipeline during rendering. To make
      effective use of the cache and facilitate rendering, it is key to represent a
      mesh in a manner that maximizes the cache hit rate. In this work, we propose a
      simple yet effective algorithm for generating a sequence for efficient rendering
      of 3D polygonal meshes based on greedy optimization. The algorithm outperforms
      the current state-of-the-art algorithms in terms of rendering efficiency of the
      resultant sequence. We also adapt it for the rendering of progressive meshes. For
      any simplified version of the original mesh, the rendering sequence is generated
      by adaptively updating the reordered sequence at full resolution. The resultant
      rendering sequence is cheap to compute and has reasonably good rendering
      performance, which is desirable to many complex rendering environments involving
      continuous rendering of meshes at various level of details. The experimental
      results on a collection of 3D meshes are provided.

PMID- 16805271
TI  - Mean square error approximation for wavelet-based semiregular mesh compression.
AB  - The objective of this paper is to propose an efficient model-based bit allocation
      process optimizing the performances of a wavelet coder for semiregular meshes.
      More precisely, this process should compute the best quantizers for the wavelet
      coefficient subbands that minimize the reconstructed mean square error for one
      specific target bitrate. In order to design a fast and low complex allocation
      process, we propose an approximation of the reconstructed mean square error
      relative to the coding of semiregular mesh geometry. This error is expressed
      directly from the quantization errors of each coefficient subband. For that
      purpose, we have to take into account the influence of the wavelet filters on the
      quantized coefficients. Furthermore, we propose a specific approximation for
      wavelet transforms based on lifting schemes. Experimentally, we show that, in
      comparison with a "naive" approximation (depending on the subband levels), using
      the proposed approximation as distortion criterion during the model-based
      allocation process improves the performances of a wavelet-based coder for any
      model, any bitrate, and any lifting scheme.

PMID- 16805272
TI  - Multifocal projection: a multiprojector technique for increasing focal depth.
AB  - In this paper, we describe a novel multifocal projection concept that applies
      conventional video projectors and camera feedback. Multiple projectors with
      differently adjusted focal planes, but overlapping image areas are used. They can
      be either differently positioned in the environment or can be integrated into a
      single projection unit. The defocus created on an arbitrary surface is estimated
      automatically for each projector pixel. If this is known, a final image with
      minimal defocus can be composed in real-time from individual pixel contributions
      of all projectors. Our technique is independent of the surfaces' geometry, color
      and texture, the environment light, as well as of the projectors' position,
      orientation, luminance, and chrominance.

PMID- 16805273
TI  - 'Building arc flash awareness' wasn't accurate.

PMID- 16805274
TI  - Safety committees: a MAP for success.

PMID- 16805275
TI  - Unidentified frying objects?

PMID- 16805276
TI  - Implementing NFPA 70E at your facility.
AB  - The likelihood of an incident with one of your workers involving an electrocution
      or electric arc flash is significantly reduced by maintaining a safe electrical
      work environment that includes three major components: proper installation, safe
      electrical work practices, and an effective, ongoing electrical maintenance
      program.

PMID- 16805277
TI  - Fit testing ear plugs.

PMID- 16805278
TI  - A new world of choices.

PMID- 16805279
TI  - Looking at total system cost.

PMID- 16805280
TI  - Extra-ore-dinary effort.

PMID- 16805281
TI  - Health care turnaround.

PMID- 16805282
TI  - The two keys to safety.

PMID- 16805283
TI  - Employee access to workplace medical and exposure records.

PMID- 16805284
TI  - Managing your most important asset.

PMID- 16805285
TI  - Transformational leadership for transformational safety.

PMID- 16805286
TI  - Back in Seattle again.

PMID- 16805287
TI  - Message received.

PMID- 16805288
TI  - Robust systems guard chemical sites.

PMID- 16805289
TI  - Confined space entry, Part 5.

PMID- 16805290
TI  - Retooling at Fluor Hanford.

PMID- 16805291
TI  - The lowdown on safe tarp handling.

PMID- 16805292
TI  - Ease the pain of hazmat regulatory compliance.

PMID- 16805293
TI  - Advocacy update. AHIMA efforts span local and national levels.

PMID- 16805294
TI  - The perils of customization.

PMID- 16805295
TI  - Getting off to a good start. Tips from the launch of two HIM systems.

PMID- 16805296
TI  - Ambulatory versus acute care EHRs. EHR systems for clinics differ from those used
      in hospitals. But does that mean they can't get along?

PMID- 16805297
TI  - Keep it clean. Optimizing EHRs starts with ensuring data quality.

PMID- 16805298
TI  - Implementation evaluation. HIM professionals share their experiences bringing
      health IT online.

PMID- 16805299
TI  - Securing genetic information. A new challenge for HIM professionals.

PMID- 16805300
TI  - Behavioral health weighs in on health IT.

PMID- 16805301
TI  - Tips for successful teamwork.

PMID- 16805302
TI  - Essential people skills for EHR implementation success.

PMID- 16805303
TI  - Physician office modifiers provide added detail for coders.

PMID- 16805304
TI  - Coding in the ambulatory surgery center.

PMID- 16805305
TI  - Where questions come from. How questions are developed for AHIMA certification
      exams.

PMID- 16805306
TI  - Working in the hybrid world. HIM director brings together multiple media, many
      perspectives.

PMID- 16805307
TI  - [The analysis of cellular elements in coelomic fluid during early regeneration of
      of the starfish Asterias rubens L].
AB  - Three main cell types were found in the coelomic fluid (CF) of intact starfishes:
      agranulocytes (55-80%) varying in size and form (spherical and ovoid) and with
      occasional pseudopodia, granulocytes (15-45%), and small cells (up to 2 %) with a
      high nuclear-cytoplasmic ratio. The starfish response to injury depends on the
      degree of coelomic fluid loss. After a slight wounding, when only insignificant
      portion of CF is lost, the cellular composition of circulating fluid changed only
      slightly. Unlike, a significant injury resulted in rising the share of small
      cells, regarded presumably as young cells. Besides, after injury the functional
      characteristics of SF also changed: the proportion of cells with decondensed
      chromatin and stained nucleoli increased, and coelomocytes acquired ability to
      form nets at adhesion. Moreover, some new cell types can be found (fusiform
      cells), with granulocyte proportion in nets increasing. We suppose that after
      slight wounding circulating coelomocytes may restore from the existing store of
      differentiated cells beyond the circulation, whereas after significant injury
      young undifferentiated coelomocytes are involved in the process of restoration.

PMID- 16805308
TI  - [Ultrastructural features of the epidermis in turbellaria from the Lake Baikal
      Geocentrophora wagini (Lecithoepitheliata, Plathelminthes)].
AB  - The epidermis of Geocentrophora wagini was studied using transmission electron
      microscopy. The turbellarian body was entirely covered by cilia, whose density
      was higher on the ventral surface compared with the dorsal one. In all regions
      examined, the epidermis was made up of a one-layered insunk epithelium. The basal
      matrix, underlying the epidermis, was a well developed basement membrane (BM)
      with bilayered structure, overlying the muscle network of circular and
      longitudinal fibers. The double plasma membranes, extending from the apical
      surface of epidermis to BM, were linked by specialized cell junctions. This
      suggested that epidermis had a cellular rather than a cyncytial arrangement. Each
      insunk epidermal cell was made of two unequal parts: a comparatively thin surface
      plate attached to BM by hemiadherens junctions, and a massive nucleated portion
      located below the body wall musculature in the parenchyma. A thin cytoplasmic
      bridge connected the epidermal plate with the nucleated cell body. The epidermal
      plates were joined by belt-like junctions along their adjacent surfaces.
      Inconspicuous zonula adherens (ZA) had a most apical position, and prominent
      septate junction was arrayed proximally to this zonula. Except ZA, cell
      boundaries in epidermis were frequently flanked by rows of light tubules and
      vesicles. In the basal half of the epithelial sheet, they were occassionally
      accompanied by single cisternae of rough endoplasmic reticulum (RER). The
      ultrastructure of the insunk cell body and that of the surface plate showed a
      considerable similarity. The common features were distinctive profiles of RER and
      GA, the presence of epitheliosomes, light tubules and vesicles, centrioles and
      fibrous granules. Thus, ultrastructural features allow a rather reliable
      identification of epidermal cells in the parenchyma, despite the absence of any
      visible morphological association between cell body and its epidermal plate.

PMID- 16805309
TI  - [The influence of protonophore high concentration on the structure and functions
      of wheat root cells].
AB  - Protonophore induced structural and functional changes in cells of excised roots
      of wheat seedlings have been investigated. The vector transfer of H+ inside the
      cells was accompanied by a decrease in energy supply of these cells (suppression
      of oxygen consumption and heat release), an output of K+ ions to the incubation
      medium, and by an increase in its pH value. The initial increase in heat release
      by roots (1 h) apparently reflects the process of dissipation of deltamicro H+ in
      plasma membrane. Within the first 5-10 min of exposure of 50 microM CCCP, changes
      in cell ultrastructure were observed that involved activation of Golgi apparatus,
      secretion of vesicle contents to the vacuole, and swelling of endoplasmic
      reticulum canals. Following a 2 h treatment with CCCP, structural and functional
      changes acquired a destructive character, and after 5-6 h of treatment with
      protonophore a complete desintegration of cell structure occurred demonstrating
      formations of myelin-like bodies, fragmentation of plasma membrane, and
      destruction of the nucleus. Thus, the protonophore induced proton excessive
      transport inside cells is fast and may cause an irreversible cell de-energization
      followed by serious disruption of ultrastructural organization of cells leading
      eventually to their death.

PMID- 16805310
TI  - [Ultrastructure of parenchymal leaf cells of different soybean varieties
      systemically infected with soybean mosaic virus].
AB  - A comparative study was made of the ultrastructure of parenchyma leaf cells of
      different soybean varieties systemically infected with soybean mosaic virus
      (SMV). It has been shown that virus accumulation and formation of virus-specific
      cylindrical inclusions (CIs) occur in the infected cells, in addition to
      intracellular changes showing stimulation of lytic processes, such as activation
      of smooth endoplasmic reticulum and Golgi apparatus, formation of cytoplasmic
      vacuoles, cytosegresomes, myelin-like bodies, different disturbances in the
      structure of cell organelles. Many infected cells demonstrated microbodies with
      invagination in which cylindrical inclusions were often found showing signs of
      destruction. It is suggested that such microbodies possess autophagic activity
      towards CIs. A possible relation of the observed virus-induced ultrastructural
      cell changes with the degree of SMV affection of investigated varieties is
      discussed

PMID- 16805311
TI  - [Macrosystemic approach in cytological studies of the urothelial urinary bladder
      using the computerized morphometry data].
AB  - The work is devoted to studying a possibility to use, for cytological diagnostics
      of urogenital neoplasms, of macrosystemic approaches, aimed to estimate cell
      systemic reactions during blasttransformation and treatment (exemplified by 95
      urinary bladder cancer patients). Changes in size of nuclear and cytoplasmic
      areas were studied, in addition to the average activity of synthetic processes or
      functional activity of cell structures, and to the level of heterogeneity of
      functional tension in the cell space.

PMID- 16805312
TI  - [Dynamics of microtubular cytoskeleton during meiosis in higher plants. VIII.
      Comparison between successive and simultaneous cytokinesis].
AB  - The abnormal cytoskeleton cycle in meiosis in pollen mother cells of cereal wide
      hybrids F reveals the role of polar microtubules in phragmoplast formation during
      successive cytokinesis. The cytoskeletal rearrangements during successive and
      simultaneous cytokinesis in higher plant meiosis are compared.

PMID- 16805313
TI  - [Transmission of ribosomal chromatin during mitosis in embryonal pig kidney cells
      (PK cell line)].
AB  - Mammalian nucleolar organizers (NORs) contain ribosomal (rRNA) genes associated
      with argyrophilic proteins and can be specifically stained by silver. These genes
      are clustered in four loci of PK meta- and submetacentric chromosomes 8 and 10.
      According to our data reported elsewhere, one of PK NORs contains a large
      amplification of rRNA that is manifested on silver stained chromosomes as
      abnormally large Ag+-NOR 8a. It is proposed that such a redundancy of rRNA genes
      induced their dose compensation in the form of transcriptional silencing,
      triggering the rise of Ag-negative ribosomal chromatin. To test this assumption,
      we carried out a morphometrical analysis of Ag+-NOR (bearing) chromosomes from
      prometaphase sets with modal chromosome number. We found that in the individual
      chromosome set a longer homologue 10L of chromosome 10 had always a larger Ag(+)
      NOR area than did a shorter homologue 10S. Thus, PK karyotype consists of two
      pairs of heteromorphous Ag(+)-NORs: 8a and 8, 10L and 10S. One half of tested
      chromosome sets revealed four Ag(+)-NOR chromosomes, the other half had one Ag
      negative NOR nearly equally belonging to chromosome either 8 or 10S. The majority
      of prometaphase Ag+-NORs showed partial or full chromatid splitting that allows
      for Ag(+)-NOR area measurements of (sister) chromatid. The area ratio of larger
      to smaller chromatid Ag(+)-NOR strongly varied for all chromosomes except
      chromosomes 8a. The maximum value of this ratio reached 5.1 for chromosome 8 and
      3.4, and 2.3--for 10L and 10S (vs. 1.6 for 8a). Proportions of chromosomes with
      the ratio 1.25 and more, were: near two thirds--among chromosomes 8, near half-
      among 10L and 10S, but less than a quarter--among chromosomes 8a. These findings
      show that progressive differentiation of sister chromatid NORs in regard of the
      content of Ag-negative ribosomal chromatin may lead to an unequal Ag(+)-NOR
      distribution between daughter cells. To test this prediction, we developed a new
      technique for obtaining two dimensional (2D) preparations of stretched PK cells,
      which makes it possible to avoid the stage of hypotonic treatment of living
      cells, since this treatment levels the silver staining of NORs and prenucleolar
      bodies of fixed telophase cells. We found that some daughter nuclei from early
      telophase cells revealed the value of Ag(+)-NOR separation equal to 4:3 instead
      of the common value equal to 4:4. Complimentary 2D FISH with 28S + 18S mink rDNA
      probe showed that early telophase rRNA loci, detected as four bright large spots,
      are close by area and shape to Ag(+)-NORs of the corresponding cells. Sometimes,
      however, one of the daughter nuclei showed three such domains, in addition to one
      slight linear FISH signal that most probably represented Ag-negative NOR. A
      delayed separation of sister chromatids is the main structural characteristic of
      inactive chromatin (Azuara et al., 2003). It was established that the largest PK
      Ag(+)-NOR (chromosome 8a) showed a high level of cohesion and (or) twisting of
      sister chromatids that is characteristic of prophase rather than prometaphase PK
      chromosomes. These findings, together with the above cited literature data, give
      evidence for enrichment of Ag(+)-NOR by either inactive or (and) low active late
      replicating chromatin.

PMID- 16805314
TI  - [Localization of repetitive DNA sequences in the pericentromeric heterochromatin
      of malarial mosquitoes of the "Anopheles maculipennis" complex].
AB  - Distribution of eight fragments of conserved repetitive DNA from pericentromeric
      heterochromatin of chromosome 2 of Anopheles atroparvus has been investigated by
      in situ hybridization on polytene chromosomes of An. atroparvus and An. messeae.
      We have shown that heterochromatic regions of all chromosomes both in An.
      atroparvus and An. messeae vary in combinations of, at least, conserved repeats.
      Some repeats have been found only in pericentromeric heterochromatic regions of
      chromosomes 2 (clones Atr2R-46a, Atr2R-73, Atr2R-85a in An. atroparvus and Atr2R
      25 in An. messeae). Others have been found in two (clones Atr2R-25a and Atr2R-90
      in An. atroparvus, Atr2R-25a in An. messeae) and more (clones Atr2R-118, Atr2R
      136 in An. atroparvus, Atr2R-73 in An. messeae) pericentromeric heterochromatic
      regions of chromosomes. DNA comparison of pericentromeric heterochromatic regions
      of chromosomes in species of the "Anopheles maculipennis" complex is species- and
      chromosome-specific, due, in particular, to different maintenance of conserved
      repeates.

PMID- 16805315
TI  - [Transcription factor ZF5 regulates expression of mammalian gene containing GCC
      triplet repeats in 5'-regulatory region in human hepatoma HepG2 cells].
AB  - Some nuclear proteins of human HeLa and HepG2 cells are capable of binding to GCC
      triplet repeats--(GCC)n > 3 in 5'-regulatory regions of a number of mammalian
      genes--G-C-elements. According to our previous data, nucleotide sequence (GCC)4
      in promoter of mouse ribosomal protein L32 gene (rpL32) between 17 and 6 bp
      upstream of transcription start site interacts to nuclear proteins from HepG2
      cells, and may be considered as a GCC-element. We suggest that one of those
      proteins, with molecular weight about 52 kDa, which may interact with rpL32 GCC
      element, is a known conservative mammalian transcription factor ZF5. DNA-binding
      domain of ZF5 contains a few Kruppel-like Zn-fingers (Cys2His2-type) interacting
      with the GC-rich nucleotide sequences in 5'-regulatory regions of a number of
      mammalian genes. Our results (obtained by EMSA) showed that recombinant GST-ZF5
      fused protein containing ZF5 DNA-binding domain specifically binds a few GS-rich
      sequences: (GCC)g-9riplet repeats, 5'-GCGCGC-3' (known ZF5 consensus binding
      site) and (more preferable) the fragment (-24...+1 bp) of rpL32 promoter. The
      high affinity of ZF5 DNA-domain binding with the latter may be explained by the
      presence in this fragment of two overlapped subsequences, each being capable of
      binding to ZF5: (GCC)4 and 5'-GCGCGC- 3'. Zf5 cDNA was cloned from HepG2 cells by
      RT-PCR method, and then used for construction of the gene expression vector. It
      has been shown that Zf5 cDNA expression vector specifically down-regulates (in
      luciferase assays) the activity of rpL32 promoter (-155...+159) including the
      above mentioned GC-rich subsequences by cotransfection of HepG2 cells. Therefore,
      our results enable us to consider GCC-elements as a novel class of ZF5 targets in
      5'-regulatory regions of mammalian genes.

PMID- 16805316
TI  - [B chromosome polymorphism of blackflies (Diptera, Simuliidae) from the north
      western region of Russia].
AB  - We have studied karyofonds of natural populations and B-chromosome morphology of
      8 species of blackflies from the North-Western region of Russia: Odagmia ornata
      Mg., Hellichiella crassa Rubz., Simulium morsitans Edw., Simulium argyreatum Mg.,
      Shoenbaueria pusilla Fries., Cnetha fontinalis Radzv., Stegopterna duo-decimata
      Rubz., and Archesimulium tuberosum Lundstr. For this purpose we made slides of
      squashed blackflies larvae with salivary gland polytene chromosomes stained by
      aceto-orcein, in addition to similarly stained slides with mitotic chromosomes
      from gonads and ganglia. Morphology of polytene B-chromosomes of Shoenbaueria
      pusilla Fries., Cnetha fontinalis Radzv., Stegopterna duodecimata Rubz., and
      Archesimulium tuberosum Lundstr. has been first described. B-chromosome
      polymorphism was found in all species, but the number of B chromosomes was
      conserved within each differences in polytene individual. Stable and distinct
      interspecific differences in the morphology of polytene B-chromosomes were
      demonstrated, and these characters are advisable to use to distinguish the
      species. We have investigated for the first time karyofonds of Od. ornata
      populations from Arkhangelsk Region (Solovetskie Islands) and Leningrad Region
      (railway station Sablino), and those of S. argyreatum populations from Murmansk
      Region (Kandalaksha environs) and Karelia (railway station Chupa). A long term
      study of Od. ornata and S. argyrestum population from North-Western Russia
      revealed interspecific and interpopulation dynamics of the occurrence of
      specimens with B-chromosomes. Some populations showed an increased percentage of
      individuals with B-chromosomes. It is suggested that B-chromosomes may play a
      role in adaptation of polulations to severe environmental conditions.

PMID- 16805317
TI  - [Antimicrobial susceptibility of Pseudomonas aeruginosa isolated from urine at
      one hospital to mainly carbapenem and fluoroquinolone drugs].
AB  - We tested the drug susceptibility to 8 anti-pseudomonal agents of 97 strains of
      Pseudomonas aeruginosa isolated from urine between January 1998 and May 2004. The
      results were as follows. 1. Antimicrobial activity was, in order of superiority
      to biapenem (BIPM), meropenem (MEPM), ciprofloxacin (CPFX), imipenem (IPM),
      pazufloxacin (PZFX), amikacin (AMK), ceftazidime (CAZ), piperacillin (PIPC). 2.
      The resistance rate (intermediate+resistance) to carbapenem drugs was 10.3% for
      BIPM and MEPM, and 13.4% for IPM. Many of the IPM-resistant strains showed
      crossover resistance with BIPM and MEPM. 3. The resistance rate
      (intermediate+resistance) to fluoroquinolone drugs was 23.7% for CPFX and 20.6%
      for PZFX. 4. One strain showed simultaneous resistance to IPM = 16 microg/mL,
      CPFX = 4 microg/mL, and AMK = 32 microg/mL, and produced IMP-1 metallo-beta
      lactamase. Susceptibility of P. aeruginosa isolated from urine developed
      resistance to fluoroquinolone drugs. It is important to promote appropriate use
      of antimicrobial agents and continue to survey emerging resistance in the
      clinical isolates.

PMID- 16805319
TI  - [Revised guideline for community acquired pneumonia].

PMID- 16805318
TI  - [Bacteria isolated from surgical infections and its susceptibilities to
      antimicrobial agents--special references to bacteria isolated between April 2003
      and March 2004].
AB  - Tendency of isolated bacteria from infections in general surgery during the
      period from April 2004 to March 2005 were investigated in a multicenter study in
      Japan, and the following results were obtained. In this series, 645 strains
      including 17 strains of Candida spp. were isolated from 226 (79.0%) of 286
      patients with surgical infections. Three hundred and seventeen strains were
      isolated from primary infections, and 345 strains were isolated from
      postoperative infections. From primary infections, anaerobic Gram-positive
      bacteria and anaerobic Gram-negative bacteria were predominant, while aerobic
      Gram-positive bacteria were predominant from postoperative infections. The
      isolation rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and
      Staphylococcus aureus were higher from both types of infections. Among anaerobic
      Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the
      highest from both types of infections. Among aerobic Gram-negative bacteria,
      Escherichia coli was the most predominantly isolated from primary infections,
      followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Citrobacter
      freundii in this order, and from postoperative infections, P. aeruginosa was the
      most predominantly isolated, followed by E. coli, E. cloacae, and K. pneumoniae.
      Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides
      fragilis group was the highest from both primary infections followed by Bilophila
      wadsworthia. While the isolation rate of B. fragilis group was also the highest
      from postoperative infections, the following bacteria were Bacteroides
      thetaiotaomicron and B. wadsworthia in this order. In this series, we noticed no
      vancomycin-resistant Gram-positive cocci, but a few strains of moderately
      arbekacin-resistant MRSA. Carbapenem-resistant P. aeruginosa but not multidrug
      resistant was seen in 13.3 per cents. Also cefazolin-resistant E. coli probably
      producing extended spectrum beta-lactamase was seen in 7.0 per cents. We should
      be carefully followed up the facts that an increasing isolation rates of B.
      fragilis group and B. wadsworthia which were resistant to both penicillins and
      cephems.

PMID- 16805320
TI  - [New strategy in development of antibiotics: GPI biosynthesis as a target].

PMID- 16805321
TI  - Increase of circulating CD8+CD57+ lymphocytes after measles infection but not
      after measles vaccination.
AB  - Natural measles virus infection is recognised to induce immunosuppression,
      contributing to an increased susceptibility to other infections. A cell
      population that could be involved in this process is the CD8CD57 double-positive
      lymphocyte subset (CD8+CD57+), known to be significantly expanded in some viral
      infections, e.g. human immunodeficiency virus (HIV) infection. We therefore
      studied the level of CD8+CD57+ lymphocytes during measles infection and measles
      vaccination. Twenty-two measles patients were examined 5-57 days after the onset
      of fever and several months later. Healthy, age-matched controls were examined
      twice. Eleven children receiving measles-mumps-rubella (MMR) vaccination were
      examined before, 9-19 days and 5-9 months afterwards. Blood samples were analysed
      for the proportion of peripheral blood mononuclear cells carrying both CD8 and
      CD57, and for other cell surface markers (CD4, CD14, CD3, CD16(CD56) or CD20).
      Elevated proportions of CD8CD57 double-positive cells were found in the
      peripheral blood of children with natural measles early after infection (p <
      0.05), whereas the proportion of other cell surface markers remained stable. No
      corresponding change in CD8+CD57+ lymphocytes was noted in MMR-vaccinated
      children or in healthy controls. Since CD8+CD57+ lymphocytes could be related to
      the immunosuppression seen in some viral infections, our finding of elevated
      CD8CD57 double-positive lymphocytes during acute measles infection would suggest
      that this population of lymphocytes is involved in measles-induced
      immunosuppression. The absence of an increase of CD8CD57 in children vaccinated
      with the conventional live attenuated measles vaccine, in contrast to children
      with natural measles infection, would thus indicate that the vaccine does not
      induce immunosuppression as measured in our in vitro system.

PMID- 16805322
TI  - An informative case of Graves' disease with implications for schizophrenia.
AB  - The aetiology of schizophrenia and the other psychoses is not yet established.
      The Knight model, based on genetic and other evidence, proposes that
      schizophrenia is an autoimmune disease, caused by the development of forbidden
      clones of B lymphocytes that secrete autoantibodies that accidentally stimulate
      cell surface receptors on certain neurons, affecting the limbic system of the
      brain. An unusual defect in a Maori man with Graves' disease rendered him
      unresponsive to the usually effective antithyroid drugs, prompting his being
      treated with prednisone, a non-specific immunosuppressant agent. This was highly
      successful, reducing the blood level of the causative thyroid-stimulating
      autoantibodies with reduction of thyroid hormone levels and thyroid gland size.
      Unfortunately, high dosage prednisone can be used for only a month, because of
      steroid toxicity. A research pathway to effective therapy of receptor-mediated
      autoimmune diseases, which probably include the psychoses, is now apparent. It
      involves finding the autoantibodies, then cloning of their antigenic targets, as
      has been done for Graves' disease. This will provide knowledge of the peptide
      sequences necessary for constructing therapeutic agents for selectively
      destroying the pathogenic forbidden clones. Meanwhile, usage of short-term
      therapy with prednisone could be helpful in the management of schizophrenia and
      should be explored.

PMID- 16805323
TI  - Policy and science of FMD control: the stakeholders' contribution to decision
      making. A call for integrated animal disease management.
AB  - Effective control of foot-and-mouth disease (FMD)--prevention, surveillance and
      response--requires integrated animal disease management as a cooperative effort
      between stakeholders, scientists and decision makers, at all levels: local,
      national, regional and international. This paper suggests a process and outlines
      specific critical issues that need to be addressed in order to best use the
      science and technology that is available now and to develop new technologies that
      will lead to significant improvements. The overall objective is not to allow the
      disease or the disease control measures to damage, violate or destroy public
      health, the environment, or the economy, or to allow politics to drive disease
      control policies at the expense of the ethical relationship between man and
      animals. Critical issues of prevention, surveillance and response policies are
      examined, and specific recommendations are made to reduce the risk or effect of
      natural and deliberate introductions. For prevention: a) rapid portable
      diagnostics and provision of vaccines to control and eradicate the reservoirs of
      disease. b) alerts, leading to increased controls at borders, animal movement
      restrictions and biosecurity on farms. For surveillance: a) reporting of unusual
      symptoms, rapid diagnostics and identification of patterns. b) enhanced role of
      geographic information systems (GIS) linked to an IT system. c) collection,
      storage and sharing of disease information. For response policies: a) the role
      and implementation of stamping out and of vaccination. b) simulation exercises
      with stakeholder participation. For all aspects of FMD control, consideration
      should be given to: a) the composition, responsibilities and role of the
      balanced, permanently operational Expert Group in EU member states as specified
      in the EU FMD Directive. b) establishment of a balanced, permanently operational
      European Expert Group. c) establishment of both a European and an International
      FMD Task Force. Stakeholders need access to accurate, up-to-date, unbiased
      information about the science of disease control, how the technologies work and
      can be used, and an assurance that the technologies best fit for the required
      purpose will be used. Researchers need to work together to avoid duplications and
      gaps in their research and to recognise the benefit of new, and sometimes
      innovative, technologies. They also need feedback from stakeholders on the
      acceptability and best use of the technologies. A process to achieve these goals
      through an EU funded collaborative research project will be described.

PMID- 16805324
TI  - The tax treatment of health insurance and employment-based health benefits.

PMID- 16805325
TI  - CMS has a lot of work to do to whip Medicare into shape.

PMID- 16805328
TI  - Pathophysiology and management of fever revisited.

PMID- 16805329
TI  - Palliative percutaneous drainage in malignant biliary obstruction. Part 1:
      indications and preprocedure evaluation.
AB  - A diagnosis of liver metastasis, periportal adenopathy, or hepatobiliary cancer
      often is accompanied by findings of biliary obstruction. Malignant biliary
      obstruction frequently is associated with pruritus, anorexia, cholangitis, or
      hyperbilirubinemia, which that precludes treatment with chemotherapeutic agents
      that are excreted or metabolized hepatically. In patients with low biliary
      obstruction, endoscopic stent placement may accomplish drainage of the entire
      biliary tree without the need for an external device. Patients with high bile
      duct obstruction, on the other hand, may need a percutaneous approach to drain
      the target ducts and avoid draining an atrophic segment or lobe. This first of a
      series of two articles concerning palliative percutaneous biliary intervention
      will review the indications for biliary drainage and the preprocedure evaluation
      of this complicated patient population.

PMID- 16805330
TI  - Arachidonic acid pathways in nociception.
AB  - The metabolism of arachidonic acid may follow multiple, inter-related pathways,
      leading to the generation or release of a wide variety of biologically active
      substances (including bradykinins, serotonin, histamine, prostaglandins, and
      cytokines) that produce pain and/or inflammation. Therapeutic agents that
      directly affect one particular pathway, such as cyclooxygenase inhibitors
      (typically, nonsteroidal anti-inflammatory agents), may indirectly affect one or
      more other pathways, as well as the resolution of inflammation. Rather than
      taking the traditional approach to treating multiple types of pain by inhibiting
      a single pathway, future treatments of pain and inflammation may target specific
      pathways and pain mechanisms and/or address two or more pathways simultaneously.
      A thorough understanding and appreciation of the mechanisms contributing to
      various pain and inflammatory states, the metabolic fates of arachidonic acid,
      the functions of its many metabolites, and the interrelatedness of the various
      metabolic pathways involved in nociception may lead to more rational and optimal
      approaches to addressing patient suffering.

PMID- 16805331
TI  - A multicenter, randomized trial of long-acting octreotide for the optimum
      prevention of chemotherapy-induced diarrhea: results of the STOP trial.
AB  - Diarrhea is a well-recognized side effect of chemotherapy and can result in
      chemotherapy delay and/or dose reduction, potentially reducing the therapeutic
      benefit of treatment. Octreotide has been shown to be effective in controlling
      chemotherapy-induced diarrhea (CID). In this open-label, randomized, multicenter
      study, designed to asses the effects of two dose levels of octreotide long-acting
      release (LAR), patients with active or prior CID and scheduled for chemotherapy
      were randomized to receive up to six doses of either 30 or 40 mg of octreotide
      LAR. The primary endpoint was the proportion of patients experiencing severe
      diarrhea during the trial. Secondary endpoints included the proportion of
      patients requiring IV fluids due to diarrhea, unscheduled visits to healthcare
      professionals due to diarrhea, and changes in primary therapy, as well as
      treatment satisfaction and quality of life. In total, 147 patients were
      randomized and received at least 1 dose; 124 patients were efficacy-evaluable.
      Baseline characters were balanced in the 30-mg and 40-mg groups with the
      exception of gender. Fewer patients in the 40-mg group compared with those in the
      30-mg group experienced severe diarrhea (61.7% vs 48.4%; P = 0.14), required IV
      fluid (31.7% vs 18.8%; P = 0.10), and had diarrhea-related unscheduled healthcare
      visits (41.7% vs. 28.1 %; P = 0.11); however, these differences were not
      statistically significant. No significant differences were observed between the
      treatment groups in either measured quality of life or treatment satisfaction.
      Adverse events were balanced between the two groups. No specific recommendations
      can be made from this trial regarding the use of 30 mg versus 40 mg of octreotide
      LAR for CID.

PMID- 16805332
TI  - The adherence to practice guidelines in the assessment of bone health in women
      with chemotherapy-induced menopause.
AB  - Premenopausal women are diagnosed with 25% of all invasive breast
      cancers;adjuvant chemotherapy given to many of this population may induce
      menopause and increase the risk of osteoporosis development. Guidelines issued by
      the American Society of Clinical Oncology recommend regular assessment of bone
      health in such women. To assess appropriate attention to bone health, we
      performed a retrospective, cross-sectional survey of young women at high risk of
      osteoporosis secondary to chemotherapy-induced premature menopause. In all, 102
      women with chemotherapy-induced menopause, 75% of whom were 40 years of age or
      younger, were asked whether they underwent screening and preventive measures for
      osteoporosis. Only 56% had discussed bone health with their healthcare providers;
      age at diagnosis, race, and use of tamoxifen were not linked to the likelihood of
      such discussions. Regular exercise was recommended to 73% of the women, calcium
      supplementation to 56%, and bone mineral density (BMD) testing to 40%.
      Approximately one half of the women regularly exercised and took a calcium
      supplement; however, over 37% of those using a supplement took less calcium than
      that recommended to prevent osteoporosis. Further, 32% reported having had BMD
      testing;women 40 years of age or younger were less likely to have had such tests
      (27%) than were older women (48%;P = 0.05). More emphasis must be given to
      educating breast cancer survivors with chemotherapy-induced menopause about bone
      health and its maintenance. Approved therapies to prevent osteoporosis probably
      are underused in this population.

PMID- 16805333
TI  - Contrasts, conflicts, and change: A case in cultural oncology.

PMID- 16805334
TI  - [Pulmonary embolism following aorto-coronary by-pass].
AB  - The authors present a case-review of a 65 year-old female patient, hospitalized
      for rest dyspnoea and collaps condition, 3 weeks following her completed aorto
      coronary by-pass. The symptoms were caused by a massive lung embolism. Upon the
      echocardiographic examination, a massive thrombus in the right-sided cardiac
      spaces--a rare complication of cardiosurgical procedures--was detected. The
      patient was treated surgically. At the present time, 4 months following the
      procedure, the patient is completely recovered.

PMID- 16805335
TI  - [Endoscopic saphenous vein harvesting for coronary artery bypass grafting].
AB  - BACKGROUND: Traditional great saphenous vein harvest for coronary artery bypass
      grafting is associated with a significant risk of impaired wound healing.
      Endoscopic saphenous vein harvesting (EVH) has been introduced in an effort to
      reduce the incidence of leg-wound complications, whereas the histological quality
      and long-term patency of harvested grafts are comparable with grafts harvested by
      means of traditional technique. METHODS: From July to December 2005, EVH was
      performed in a group of 60 patients employing the Vasoview 6 system (Guidant,
      Europe S.A., Belgium). Patients were evaluated on 7th postoperative day for wound
      healing disturbances, residual leg oedema and saphenous neuropathy. RESULTS: The
      mean age was 67.4 +/- 11.2 years, male patients dominated (68%). At least one
      independent risk factor of leg-wound disturbances such as obesity, diabetes,
      peripheral vascular disease and female gender, was presented in 39 patients
      (63%). The mean number of harvested venous grafts was 2.0 +/- 1.2 and the mean
      total vein harvesting time was 46.2 +/- 7.4. In one case (1.7%), EVH was
      converted to the traditional harvesting technique due to superficial course of
      the great saphenous vein. The presence of wound haematoma was noted in 31
      patients (51%). No other wound disturbances such as wound infection, wound
      dehiscence, skin necrosis, lymphatic wound drainage, nor saphenous neuropathy
      were recorded in the group of patients. The leg oedema associated with EVH was
      presented in 7 patients (12%). CONCLUSIONS: EVH is a safe method associated with
      a significant reduction of leg-wound complications, residual leg oedema and
      saphenous neuropathy. EVH should become method of choice, particularly in the
      presence of independent risk factors of leg-wound disturbances. The quality and
      the harvesting time of harvested grafts were comparable to grafts harvested by
      means of the traditional harvesting technique.

PMID- 16805336
TI  - [Resection of metastatic nondifferentiated carcinoma of sternum with thoracic
      wall reconstruction and simultaneous myocardial revascularization for ischemic
      heart disease--case report].
AB  - Authors offer the case report of a patient with metastatic non differentiated
      carcinoma of sternum simultaneously suffering from ischemic heart disease. The
      patient underwent actinotherapy & hyperthermia followed by resection of sternum
      and coronary artery bypass grafting in one session. Chest wall defect was closed
      by means of latissimus dorsi muscle rotation. Postoperative palliative
      chemotherapy started 16 weeks postoperatively. Primary tumor was not found,
      neither preoperatively nor during the 36 months' postoperative remission.

PMID- 16805337
TI  - [Tracheal tumor--a case review].
AB  - Tracheal tumors make a histologically variant group of tumors. Our case review
      describes a case of a forty-five year-old female patient with an endoscopically
      and CT- diagnosed tracheal tumor. The patient was hospitalized at the IInd
      Surgical Clinic of the UPJS LF, the Faculty Hospital of L. Pasteur in Kosice,
      with symptoms of dyspnoea and stridor, in the orthopnoic position. Following the
      neccessary pre- operative procedures, her trachea was resected, followed by end
      to-end anastomosis. The histological examination of the resected tissue revealed
      an inflammatory myofibroblastic tumor. The postoperative course was positive with
      no complications.

PMID- 16805338
TI  - [Unusual mechanism of the onset of a brachial artery aneurysm--a case review].
AB  - The authors present the case report of a 78-years-old man who was admitted to our
      clinic with the diagnosis of acute recurrent upper limb ischemia. The cause was
      rather rare diagnosis of a brachial artery aneurysm. The etiology of the aneurysm
      was interesting--70 years using of a arm-pit crutch.

PMID- 16805339
TI  - [Initial experience with da Vinci robotic system in vascular surgery].
AB  - Robotic operational systems improve accuracy, control of and skilful management
      of surgical procedures up to levels unachievable by a human factor itself. A
      surgeon is also allowed to conduct the types of miniinvasive procedures, which
      cannot be conducted using contemporary technologies. High degree of the
      procedure's safety can be achieved. Currently, the robotic surgical systems are
      used in top clinics worldwide and the concept of the robotic operating theatre is
      considered to become standard for some procedures in future. In October 2005, a
      multispecialist robotic centre was opened in the Hospital Na Homolce, which then
      created a new qualitative standard in the miniinvasive surgical management. The
      authors present the initial group of patients, who were operated from November
      2005 to January 2006 with employement of the da Vinci robotic system, listing its
      pros and cons.

PMID- 16805340
TI  - [Laparoscopic rectopexis].
AB  - INTRODUCTION: Rektopexis is an effective treatment method of rectal prolapses.
      Our retrospective study assessed the laparoscopic rectopexis results.
      METHODOLOGY: From 01-01-2003 to 31-11-2005, 10 patients were indicated for the
      procedure of laparoscopic retropexis. A "Vypro" mesh (Johnson&Johnson) was used
      to suspend the rectum. We fix it to the sacrum and to the rectum with an anchor
      (Eanchr, Johnson&Johnson). The follow-up examinations were conducted 2-30 months
      after the procedure. We assessed mortality rates, morbidity rates, the prolaps
      relapses incidence rates, obstipation incidence rates. RESULTS: The laparoscopic
      procedure was completed in 9 patients. In one case, we converted. The mortality
      and serious postoperative morbidity rate was 0%. The mean duration of
      hospitalization was 7 days. During the follow-up, no patient relapsed. One female
      patient complained of mild postoperative obstipation, which, however, did not
      require surgical revision. CONCLUSION: Laparoscopic rectopexis is a modern, safe
      and effective method of the prolaps of the rectum treatment.

PMID- 16805341
TI  - [Percutaneous cholecystostomy in acute cholecystitis--a solution for risk patient
      groups?].
AB  - In treating acute cholecystitis in patients with a high operative risk, the
      general rule is to treat conservatively, with surgery indicated in those patients
      where this therapy is insufficient. Cholecystotomy is one alternative method of
      treatment. Due to its disadvantages, it belongs to one of the most seldomly used
      surgical procedures. These drawbacks, however, may be curtailed by using a
      percutaneous cholecystotomy (PC) done under CT or US navigation. The authors here
      recount their experiences of treating acute cholecystitis with PC in two case
      studies, relating difficulties in indication, technical performance, and
      complications of the procedure. In accordance with scientific literature, we
      consider PC an effective treatment method with minimal complications.

PMID- 16805342
TI  - [Technical aspects of the liver resection procedure--options for combinations of
      individual methods].
AB  - INTRODUCTION: The liver resection procedure as a treatment method of benign and
      malignant hepatobiliary disorders grows more important due to the fact, that its
      postoperative morbidity and mortality rates have been reduced, a result of the
      patients selection method, surgical techniques and perioperative care
      improvements. The aim of this report was to assess combinations of recent liver
      transsection techniques, based on the authors' own experience and results of
      recent studies. MATERIAL, METHODS AND RESULTS: From 1999 to May 2005, in the
      Surgical Clinic of the Faculty Hospital Kralovske Vinohrady in Prague, the liver
      resection procedure was completed in 133 patients with benign or primary and
      secondary malignant tumors. In the liver transsection procedure, the following
      instrumentation was used, starting from 1999: harmonic scalpels, ultrasonographic
      dissectors, water jet scalpel, bipolar diathermia, argon coagulation and
      radiofrequency. The liver tissue dissection using the ultrasonographic dissector
      or the water jet scalpel in combination with the harmonic scalpel or bipolar
      diathemic coagulation, reduced the postoperative blood loss in extensive non
      anatomical liver resections. This dissection method was also used in some
      "centrally" located tumors for their non-anatomical resections. The benefit of
      the combination of the methods is based on sufficient coagulation and
      interruption of minor vascular branches and bile ducts in the resection line,
      without intermittent closure of the blood influx to the liver, using a Pringle
      manoeuvre. The radiofrequency, as a novel method for the liver tumors ablation,
      was used in anatomical and non-anatomical liver resections to coagulate the liver
      tissue prior to its transection prior to the R0 resection. The postoperative
      morbidity rate was 14% (19 patients). Within 30 postoperative days, no death was
      recorded. CONCLUSION: 1. The above listed liver transsection techniques,
      employing the ultrasonographic dissector or water jet scalpel, are safe
      alternative liver resection methods, reducing the blood loss. 2. Diathermic
      coagulation is an alternative to the harmonic scalpel for intersecting minor
      intraparenchymatous vascular branches and bile ducts. 3. A combination of the
      ultrasonographic dissector technique or water jet scalpel with the harmonic
      scalpel or diathermic coagulation technique, aids the liver resection by closing
      and interrupting the vessels and bile ducts in the resection line. 4.
      Radiofrequency and pre-transsectional coagulation of the liver parenchyma reduces
      the bleeding during the resection procedure and is a method of choice in
      resections of centrally located tumors, reducing the loss of the functional
      parenchyma.

PMID- 16805343
TI  - [Idiopatic bowel disease].
AB  - On the basis of retrospective five years analysis the authors process the
      problematic of idiopatic bowel disease--Morbus Crohn and ulcerative colitis. They
      pay main attention to surgical issue--types of operations, differences between
      acute and elective surgery, perioperative problems and results.

PMID- 16805344
TI  - [Pancreatectoduodenectomy for multiple duodenal diverticula. Case report].
AB  - The authors present a case report of a 61-years old female with 12 month history
      of deteriorative chronic pain located in epigastrium and propagating to her back,
      tabescence and upper dyspeptic syndrome. The first grade oesophagitis and
      duodenogastric reflux were verified endoscopically. There were adequate biliary
      tree as well as pancreatic duct and two high-volumed parapapillar diverticula and
      the third one in the region of D 3 depicted by ERCP and enteroclysis. Neither
      ultrasound nor computed tomography detected any pancreatic or hepatic pathology.
      All the alternatives of internal medical treatment resulted in no effect. The
      surgical treatment lied in performance of pylorus-saving pancreatoduodenectomy
      (Traverso-Longmire). Five months after operation the patient suffers from no
      ailments and prospers in general. The authors render an account of duodenal
      diverticula surgical treatment.

PMID- 16805345
TI  - Atraumatic ridge expansion and implant site preparation with motorized bone
      expanders.
AB  - The osteotome technique has been utilized for many years as a viable approach to
      expand atrophic ridges. Despite its effectiveness, the mechanical impact from the
      surgical mallet is not well tolerated by patients. Additionally, reports in the
      literature describe postoperative complications that include concussions and
      benign paroxysmal vertigo. These conditions can be alarming for the patient and
      clinician, as their effects may persist for several weeks. A new technique for
      atraumatic ridge expansion has been developed that introduces the surgical use of
      motor-driven instruments at low speeds.

PMID- 16805346
TI  - Intracoronal restorations--part I: direct procedures.

PMID- 16805347
TI  - Revisiting basic life support: 2005 consensus on CPR.

PMID- 16805348
TI  - A ten-unit all-ceramic anterior fixed partial denture using Y-TZP zirconia.
AB  - High-strength, all-ceramic systems are being recommended with increasing
      frequency for both anterior and posterior restorations. There are some
      significant differences in the physical and mechanical properties of these
      materials that ultimately affect their clinical performances. Consequently, these
      differences should be clearly understood before the restorative team selects the
      use of a particular system. This article reviews these differences and
      demonstrates the use of Y-TZP zirconia for the fabrication of a 10-unit anterior
      fixed partial denture.

PMID- 16805349
TI  - Practice efficiency using digital radiography.

PMID- 16805350
TI  - Recent advances and future directives in pulp biology.

PMID- 16805351
TI  - Optimizing shade match using all-ceramic and composite materials.
AB  - Aesthetic management of the anterior dentition often requires the restorative
      team to use materials of varying color properties. The utilization of shade
      selection devices to assist in color interpretation along with dental photography
      can improve communication between dentist and technician. Additionally, a shade
      guide system that addresses the four components of color in both ceramics and
      composites can have a profound impact on the predictability of matching different
      restorative materials. This article addresses several key elements that should be
      considered when utilizing different restorative media.

PMID- 16805353
TI  - Media literacy and the web: the good, the bad, and the ugly.

PMID- 16805352
TI  - Incorporating flowable composites into the minimally invasive treatment sequence
      for aesthetic enhancement.
AB  - The conservative correction of stained anterior dentition is well-suited to
      minimally invasive techniques that first incorporate in-office, light-activated
      bleaching, and take-home, dentist-monitored tray bleaching. The second most
      conservative approach is the placement of direct composite restoratives,
      including recently introduced flowable varieties that help the clinician more
      precisely and predictably place these materials. This article demonstrates a
      conservative treatment sequence for in-office bleaching and direct composite
      placement for the aesthetic correction of discolored anterior maxillary
      dentition.

PMID- 16805354
TI  - Molar incisor hypomineralization: review and recommendations for clinical
      management.
AB  - Molar incisor hypomineralization (MIH) describes the clinical picture of
      hypomineralization of systemic origin affecting one or more first permanent
      molars (FPMs) that are associated frequently with affected incisors. Etiological
      associations with systemic conditions or environmental insults during the child's
      first 3 years have been implicated. The complex care involved in treating
      affected children must address their behavior and anxiety, aiming to provide a
      durable restoration under pain-free conditions. The challenges include adequate
      anaesthesia, suitable cavity design, and choice of restorative materials.
      Restorations in hypomineralized molars appear to fail frequently; there is little
      evidence-based literature to facilitate clinical decisions on cavity design and
      material choice. A 6-step approach to management is described: (1) risk
      identification; (2) early diagnosis; (3) remineralization and desensitization;
      (4) prevention of caries and posteruption breakdown; (5) restorations and
      extractions; and (6) maintenance. The high prevalence of MIH indicates the need
      for research to clarify etiological factors and improve the durability of
      restorations in affected teeth. The purpose of this paper was to describe the
      diagnosis, prevalence, putative etiological factors, and features of
      hypomineralized enamel in molar incisor hypomineralization and to present a
      sequential approach to management.

PMID- 16805355
TI  - Microshear bond strength of resin composite to teeth affected by molar
      hypomineralization using 2 adhesive systems.
AB  - PURPOSE: When restoring hypomineralized first permanent molars, placement of cavo
      surface margins can be difficult to ascertain due to uncertainty of the bonding
      capability of the tooth surface. The purpose of this study was to investigate the
      adhesion of resin composite bonded to control and hypomineralized enamel with an
      all-etch single-bottle adhesive or self-etching primer adhesive. METHODS:
      Specimens of control enamel (N=44) and hypomineralized enamel (N=45) had a 0.975
      mm diameter composite rod (Filtek Supreme Universal Restorative) bonded with
      either 3M ESPE Single Bond or Clearfil SE Bond following manufacturers'
      instructions. Specimens were stressed in shear at 1 mm/min to failure (microshear
      bond strength). Etched enamel surfaces and enamel-adhesive interfaces were
      examined under scanning electron microscopy. RESULTS: The microshear bond
      strength (MPa) of resin composite bonded to hypomineralized enamel was
      significantly lower than for control enamel (3M ESPE Single Bond=7.08 +/- 4.90 vs
      16.27 +/- 10.04; Clearfil SE Bond=10.39 +/- 7.56 vs 19.63 +/- 7.42; P=.001).
      Fractures were predominantly adhesive in control enamel and cohesive in
      hypomineralized enamel. Scotchbond etchant produced deep interprismatic and
      intercrystal porosity in control enamel and shallow etch patterns with minimal
      intercrystal porosity in hypomineralized enamel. Control enamel appeared almost
      unaffected by SE Primer; hypomineralized enamel showed shallow etching. The
      hypomineralized enamel-adhesive interface was porous with cracks in the enamel.
      The control enamel-adhesive interface displayed a hybrid layer of even thickness.
      CONCLUSIONS: The microshear bond strength of resin composite bonded to
      hypomineralized enamel was significantly lower than for control enamel. This was
      supported by differences seen in etch patterns and at the enamel-adhesive
      interface.

PMID- 16805356
TI  - Effectiveness of two nitrous oxide scavenging nasal hoods during routine
      pediatric dental treatment.
AB  - PURPOSE: This study compared the effectiveness of 2 nasal hoods (Porter/Brown and
      Accutron) in reducing waste nitrous oxide gas during conscious sedation for
      routine pediatric dental treatment. METHODS: Thirty children, ages 3 to 8 years
      (mean=5.4 +/- 1.2 years), participated in this study. Fifteen randomly selected
      children started with the Porter/Brown mask, which was then switched to the
      Accutron mask, and the other 15 children used the reverse order of masks. Four
      measurements of ambient nitrous oxide were recorded with a Miran 205B Portable
      Ambient Air Analyzer 5 minutes after each of the following: (1) administration of
      nitrous oxide; (2) placement of the rubber dam; (3) change of the nasal hood; and
      (4) reduction of the vacuum. Samples were taken 8 inches above the nose of the
      patient and in the room 5 feet away from the patient. RESULTS: Nitrous oxide
      levels were significantly lower (P<.05) with the Porter/Brown system (31 +/- 40
      ppm for the patient and 8 +/- 10 ppm for the room) compared with the Accutron
      system (375 +/- 94 ppm for the patient and 101 +/- 37 ppm for the room). When the
      suction was reduced, there was an increase in nitrous oxide levels with the
      Porter/Brown nasal hood (169 +/- 112 ppm for the patient and 28 +/- 18 ppm for
      the room), whereas the levels with the Accutron nasal hood remained high (368 +/-
      107 ppm for the patient and 121 +/- 50 ppm for the room). CONCLUSIONS: This study
      demonstrated that removal of waste nitrous oxide was greater with the
      Porter/Brown device and that recommended suction levels must be used for optimum
      effectiveness.

PMID- 16805357
TI  - Comparison of apexification with mineral trioxide aggregate and calcium
      hydroxide.
AB  - PURPOSE: The aim of this study was to compare mineral trioxide aggregate (MTA)
      with calcium hydroxide [Ca(OH)2] clinically and radiographically as materials
      used to induce root-end closure in necrotic permanent teeth with immature apices
      (apexification). METHODS: Fifteen children, each with at least 2 necrotic
      permanent teeth requiring root-end closure (apexification), were selected for
      this study. All selected teeth were evenly divided into 2 test groups. In group
      1, the conventional calcium hydroxide apexification (control) was performed,
      whereas in group 2, the MTA apexification (experimental) was done. The children
      were recalled for clinical and radiographic evaluations after 3, 6, and 12
      months. RESULTS: The follow-up evaluations revealed failure due to persistent
      periradicular inflammation and tenderness to percussion detected at 6 and 12
      months postoperative evaluation in only 2 teeth treated with Ca(OH)2. The
      remaining 13 teeth appeared to be clinically and radiographically successful 12
      months postoperatively. None of the MTA-treated teeth showed any clinical or
      radiographic pathology. CONCLUSIONS: Mineral trioxide aggregate showed clinical
      and radiographic success as a material used to induce root-end closure and is a
      suitable replacement for calcium hydroxide for the apexification procedure.

PMID- 16805358
TI  - Malnourishment in a population of young children with severe early childhood
      caries.
AB  - PURPOSE: The purpose of this study was to describe the nutritional status of
      children with severe early childhood caries (S-ECC) using several clinical
      measurements. METHODS: Children aged 2 to 6 years with S-ECC were measured for
      height, weight, triceps skinfolds (TSF), and measurement of upper mid-arm
      circumference (MAC). Blood samples assessed: (1) hemoglobin; (2) mean corpuscular
      volume (MCV); (3) serum ferritin; and (4) serum albumin. Weight-for-height was
      converted into ideal body weight (IBW) percentiles. Body mass index (BMI) was
      calculated as kg/m2. TSF and MAC were converted into measurement of arm muscle
      circumference (MAMC). All measurements were compared with population reference
      values. RESULTS: Using weight for height centiles, 17% were diagnosed as being
      malnourished and 66% as within normal limits. Using BMI centiles, only 4% were
      identified as being malnourished and 75% as being normal. Conversely, the body
      fat of 24% was assessed as low (<10th percentile). Serum albumin was low for 16%.
      The majority had evidence of inadequate iron intake with low serum ferritin
      (80%), iron depletion (24%), iron deficiency (6%), or iron deficiency anemia
      (11%). CONCLUSIONS: All tests detected levels of malnutrition, with blood tests
      finding the most severe cases. The results suggest that severe Early Childhood
      Caries may be a risk marker for iron deficiency anemia. Since iron deficiency has
      permanent effects on growth and development, pediatric dentists should recommend
      assessment of iron levels in S-ECC patients regardless of their anthropometric
      appearance.

PMID- 16805360
TI  - Dental management of a child with trisomy 9 mosaicism: a case report.
AB  - This case report presents the dental management of a 13-year-old girl with mosaic
      trisomy 9. She had: (1) severe psychomotor retardation; (2) short stature; (3)
      progressive microcephaly; (4) flat feet; (5) genu valgum; and (6) severe
      kyphoscoliosis. Dysmorphic facial features included: (1) maxillary prognathism;
      (2) narrow high-arched palate; (3) short philtrum; (4) small low posterior
      dysplastic ears; and (5) down slanting palpebral fissures with right eye ptosis.
      The case report describes initial treatment under general anesthesia and further
      treatments using conscious sedation. Emphasis was placed on the need to adjust
      the treatment to patient's skeletal malformations and respiratory problems by
      adjusting her ability to sit in the dental chair in an upright position.
      Supernumerary premolars and opalescent changes of the maxillary incisors might be
      part of the clinical features related to trisomy 9 mosaic syndrome.

PMID- 16805359
TI  - Children sedated for dental care: a pilot study of the 24-hour postsedation
      period.
AB  - PURPOSE: The purpose of this prospective, pilot study was to investigate
      postsedation events during the first 24 hours after discharge from the treatment
      facility in children sedated for dental treatment. METHODS: This prospective
      study involved a convenience sample of 30 healthy patients, ranging from 2 to 5
      years of age, who were scheduled to undergo sedation in the dental clinic for
      operative procedures. Depending on the extent of dental need, child temperament,
      and other preoperative assessment variables, the children received either a
      triple combination of chloral hydrate, meperidine, and hydroxyzine ranging in
      dose from 20 to 30 mg/kg, 1 to 2 mg/kg, 1 to 2 mg/kg, respectively, or midazolam
      alone (0.5-0.75 mg/kg). Care was provided consistent with the American Academy of
      Pediatric Dentistry (AAPD) and hospital sedation guidelines. Parents were given a
      questionnaire concerning events that may occur during the 24 hours after the
      sedation and were told they would be interviewed via telephone regarding these
      events. The principal investigator called 24 hours after the sedation visit and
      interviewed the parents using the questionnaire given to the parents. Data
      analysis included descriptive statistics, frequency, and chi-square analysis.
      RESULTS: Data from 30 sedations were used. Differences were noted between a
      chloral hydrate, meperidine, and hydroxyzine regimen compared to midazolam alone
      for incidence of sleep on the way home or shortly after arriving at home, but not
      for postoperative pain, vomiting, eating, evening sleep, and memory. Those
      receiving the combination regimen were more likely to sleep on the way to and at
      home than those who received midazolam alone. CONCLUSIONS: It may be concluded
      that: (1) opportunities for the occurrence of an adverse event may occur on the
      way or at home following a sedation appointment; and (2) discharge criteria of
      the AAPD guidelines on elective use of minimal, moderate, or deep sedation and
      general anesthesia for pediatric dental patients should be met or exceeded as a
      precautionary measure to prevent adverse events once a child who has received
      sedative agents leaves a health care facility.

PMID- 16805361
TI  - Dentigerous cysts in primary dentition: report of 2 cases.
AB  - Dentigerous cysts are benign odontogenic cysts associated with the crowns of
      permanent teeth. They are usually single in occurrence and located in the
      mandible. The purpose of this case report was to describe the management of 2
      dentigerous cysts in children. The treatments instituted were the extraction of
      the deciduous tooth involved followed by marsupialization in the first case and
      enucleation in the second one. Both treatments allowed rapid healing of the
      lesion and eruption of the permanent teeth without the need for orthodontic
      treatment.

PMID- 16805362
TI  - The complete endodontic obturation of an avulsed immature permanent incisor with
      mineral trioxide aggregate: a case report.
AB  - The use of mineral trioxide aggregate (MTA) for complete endodontic obturation of
      an immature maxillary central incisor is reported. The injured tooth of a 9-year
      old male was avulsed secondary to a sports-related traumatic event. Early
      attempts at pulpal revascularization of the replanted tooth proved unsuccessful,
      as evidenced by radiographic signs of external inflammatory root resorption in
      the middle to cervical thirds of the root. Calcium hydroxide apexification over a
      1-year period promoted cessation of the resorptive process, but was unable to
      adequately form an apical root canal barrier. Due to the extent of external
      resorption and the lack of an apical stop, a novel endodontic treatment using
      mineral trioxide aggregate was utilized. At 865 days post-injury, the tooth
      remained asymptomatic with clinical and radiographic evidence of periodontal
      health.

PMID- 16805363
TI  - Oral and dental manifestations of gastroesophageal reflux disease in children: a
      preliminary study.
AB  - PURPOSE: The aim of this study was to investigate the effects of gastroeophageal
      reflux disease (GERD) on: (1) erosion; (2) caries formation; (3) salivary
      function; and (4) salivary microbiological counts. METHODS: Thirty-eight GERD
      patients with a mean age of 6 1/2 years and 42 healthy children of the same age
      and gender and social background comprised the study group. All subjects answered
      a detailed frequency questionnaire related to acidic drinks, foods, and sugar
      consumption and participated in a clinical dental examination. The caries
      experience of the children was recorded according to World Health Organization
      criteria, and erosion was scored according to the Eccles and Jenkins grading
      scale. The children were also investigated for stimulated salivary flow rate,
      buffer capacity, and salivary mutans streptococci (MS), lactobacilli, and yeast
      colonization. RESULTS: The prevalence of dental erosion and the salivary yeast
      and MS colonization in GERD children was found to be significantly higher than
      for healthy subjects (P<.05). The caries experience, salivary flow rate,
      buffering capacities of the children, and frequency of acidic drinks, foods, and
      sugar consumption were found to be similar in both groups. CONCLUSION: This
      current investigation has shown that GERD children were at an increased risk of
      developing erosion and caries compared with healthy subjects.

PMID- 16805364
TI  - Factors influencing the use of dental health services by preschool children in
      Mexico.
AB  - PURPOSE: The purpose of this study was to identify the factors associated with
      dental health services utilization (DHSU) within a publicly funded oral health
      program for preschool children in Campeche, Mexico. METHODS: A cross-sectional
      study in 1,303 preschoolers (3 to 6 years old) enrolled in 10 public schools was
      conducted. The independent variables were: (1) sex; (2) age; (3) tooth-brushing
      frequency; (4) caries severity; (5) enamel defects; (6) mother's maximum
      education level; (7) mother's attitude toward oral health; (8) health services
      availability; and (9) family's socioeconomic status. The mothers completed a
      questionnaire, and their children were clinically examined. The DHSU (none vs
      any) in the previous 12 months was the dependent variable. Data were analyzed
      using binary logistic regression (BLR). RESULTS: Average age was 4.3 +/- 0.8
      years, and 52% of participants were boys. The prevalence of DHSU any was 31%. The
      variables associated with DHSU were: (1) moderate and high oral health needs; (2)
      access to private health services; and (3) older age. The authors' model
      supported an interaction between tooth-brushing frequency and the importance that
      the mother ascribed to her child's oral health. CONCLUSIONS: A low prevalence of
      DHSU was observed. The source of health services and oral health needs determined
      DHSU in this population, with some attitudes and behaviours modifying
      utilization. These findings have implications for designing oral health care
      policies to improve the supply of services to children.

PMID- 16805365
TI  - Association of chairs of departments of physiology 2005 survey results.

PMID- 16805366
TI  - AAMC Medical School Faculty Compensation Survey.

PMID- 16805367
TI  - American physiological society draft strategic plan 2006-2010.

PMID- 16805368
TI  - IUPS--a retrospective.

PMID- 16805369
TI  - The academic practice of otolaryngology: philosophical and practical
      perspectives.
AB  - The academic practice of otolaryngology does not end after residency, nor does it
      depend upon employment in an academic institution or affiliate. Academic practice
      is a state of mind and a mode of living. It is a commitment to intellectual
      vitality, and to recognizing, but never accepting, the limits of our knowledge.
      It is a call to keep asking questions and to pursue answers methodically, and it
      is a commitment for each of us to leave the field of otolaryngology better than
      we found it.

PMID- 16805370
TI  - Nonsurgical management of pediatric tracheal perforation.
AB  - Tracheal perforation is a rare complication of intubation. In the pediatric
      population, the rates of morbidity and mortality are high if diagnosis and
      management are delayed. Recommendations for treatment in these patients are based
      on the several reports of this injury in the adult and neonate populations.
      Surgical repair is generally favored over conservative care in the majority of
      cases. We describe the case of a 10-year-old girl who presented with subcutaneous
      emphysema after intubation in the emergency department. The patient had a 3-cm
      injury to the distal trachea. Nonsurgical management resulted in a normal
      appearing trachea and a healed perforation site as confirmed by repeat
      tracheobronchoscopy 4 months after the initial injury. In clinically stable
      pediatric patients, nonsurgical management of tracheal perforations should be
      considered.

PMID- 16805371
TI  - Fabry's disease: otoneurologic findings in twelve members of one family.
AB  - Fabry's disease corresponds to an inherited disorder transmitted by an X-linked
      recessive gene. It generates a dysfunction of glycosphingolipid metabolism due to
      an enzymatic deficiency of alpha-galactosidase activity, resulting in
      glycosphingolipid deposits in all areas of the body. The clinical (heart, kidney,
      and central nervous system) manifestations are more severe in hemizygous boys
      than in heterozygous girls. They appear during childhood or adolescence:
      acroparesthesia, joint pain, angiokeratoma, corneal dystrophy, hypohydrosis or
      anhydrosis, and renal failure. The otoneurologic symptoms consist of hearing
      fluctuation, progressive unilateral or bilateral hearing loss, and episodes of
      vertigo or dizziness. Otoneurologic findings in 12 of 26 members of the same
      family are presented: the mother and 9 of her 12 children, as well as 2 of her 14
      grandchildren: 4 healthy persons, 4 heterozygous female carriers, and 4
      hemizygous male patients. Three of the male patients had fluctuation of hearing,
      sudden hearing loss, and episodes of vertigo and dizziness. The otoneurologic
      examinations showed a bilateral cochleovestibular deficit (n = 1), a right
      cochleovestibular deficit (n = 1), and a bilateral hearing loss combined with a
      right vestibular deficit (n = 1). Histopathologic evidence of glycosphingolipid
      accumulation in vascular endothelial and ganglion cells, as well as atrophy of
      the stria and spiral ligament, might explain the otoneurologic symptoms and
      findings.

PMID- 16805372
TI  - Supracricoid partial laryngectomy with cricohyoidoepiglottopexy for recurrent
      laryngeal cancer.
AB  - OBJECTIVES: Recurrent laryngeal cancer can be treated either with total
      laryngectomy or in selected cases with supracricoid laryngectomy with
      cricohyoidoepiglottopexy (CHEP). We performed a retrospective study to analyze
      the functional and oncological results of supracricoid laryngectomy with CHEP.
      METHODS: Fourteen patients were treated with supracricoid laryngectomy with CHEP.
      In 8 patients, flexible endoscopic evaluation of swallowing was performed.
      Preoperative and postoperative voice evaluation was performed in 5 patients.
      Oncological and functional follow-up, postoperative complications, and data
      concerning rehabilitation were recorded on standard forms. RESULTS: After the
      supracricoid laryngectomy with CHEP, 11 of the 14 patients were alive and disease
      free. No local recurrences were found, but 2 patients had regional recurrences.
      The voice was worse after the operation; however, most patients were satisfied.
      Swallowing was uncompromised. CONCLUSIONS: Supracricoid laryngectomy with CHEP
      for recurrent glottic laryngeal cancer after radiotherapy appears to be
      oncologically safe and functional.

PMID- 16805373
TI  - Effects of converting bilateral cochlear implant subjects to a strategy with
      increased rate and number of channels.
AB  - OBJECTIVES: Three different Advanced Bionics processing strategies were
      evaluated: 1) 8-channel, 813 pulses per second (pps), Continuous Interleaved
      Sampling (CIS); 2) 16-channel, 5,100 pps, HiResolution Paired (HiRes P); and 3)
      16-channel, 2,900 pps, HiResolution Sequential (HiRes S). METHODS: Seven adult
      bilateral Clarion CII cochlear implant recipients who had been using a CIS
      processing strategy for at least 18 months participated in this study. Sentence
      recognition in multitalker babble from the front was collected on subjects using
      their CIS strategy and after subjects were programmed for the first time with
      HiRes P and HiRes S strategies. An ABAB design was implemented for 1 month
      whereby subjects used each HiResolution strategy every other day. Sentence
      recognition testing was repeated at the 1- and 3-month post-HiResolution test
      intervals. RESULTS: Comparisons between the CIS and HiResolution strategies
      showed immediate improvements for 5 subjects in favor of the HiResolution
      strategies. After 1 month of alternating between the HiRes P and HiRes S
      strategies, remarkably, 2 subjects showed improvements of 60%, 2 subjects showed
      improvements of 40%, and 2 subjects showed improvements of 30% over the CIS
      strategy that they had previously used for at least 18 months. The results after
      3 months of use were consistent with those obtained at 1 month. CONCLUSIONS: The
      HiRes S and HiRes P strategies resulted in dramatic improvements in speech
      perception in noise for a subset of subjects who had been using the CIS strategy
      bilaterally. This finding demonstrates that these subjects were able to tolerate
      a more difficult signal-to-noise ratio. Further work is needed to determine the
      independent effects of rate versus number of channels.

PMID- 16805374
TI  - Early oral feeds in laryngectomized patients.
AB  - OBJECTIVES: It is a common practice to start oral feeding after 7 to 10 days in
      patients who have undergone laryngeal surgeries. It was our observation that when
      oral feeds were initiated earlier than this period, there was no increase in the
      incidence of pharyngocutaneous fistulas. This prospective study is about our
      experience in initiating early oral feeds in the postoperative period (on the 2nd
      day) in laryngectomized patients. METHODS: Seventy-eight patients underwent
      laryngectomy with or without partial pharyngectomy over a period of 38 months
      between October 2001 and December 2004. The oral feeds were initiated on the 2nd
      postoperative day in 40 patients. Thirty-eight patients served as controls in
      whom feeds were initiated after the 10th postoperative day. RESULTS: Only 1
      patient in the study group and 2 patients in the control group developed
      pharyngocutaneous fistulas. Most patients in the control group wished to avoid
      nasogastric intubation in the recovery period because of discomfort, gastric
      symptoms, and the need to taste food. CONCLUSIONS: With this study we can assume
      that in a select group of patients, it is possible to initiate oral feeding much
      earlier in the postoperative period than was formerly thought.

PMID- 16805375
TI  - Laryngoscopy in bilateral vocal fold immobility: can you make a diagnosis?
AB  - OBJECTIVES: This study explores whether videoendoscopic findings and patient
      history help make the diagnosis in bilateral vocal fold immobility (BVFI).
      METHODS: Medical records from 1995 to 2003 were searched to identify patients
      with posterior glottic stenosis (PGS) and bilateral vocal fold paralysis (BVFP)
      who also had videoendoscopic examinations. Videoendoscopic examination findings
      that could help differentiate PGS from BVFP were identified a priori. A weighted
      scoring index, based on the adjusted odds ratios of significant examination
      findings on multiple logistic regression, was derived. Associations between the
      weighted scoring index, patient history, and diagnosis were then evaluated.
      RESULTS: Twenty-six patients with BVFP and 28 patients with PGS were identified.
      Posterior glottic scar (weight = 2), medial arytenoid erosion with a widened
      posterior glottis (weight = 1), and appropriate vocal fold motion (weight = 1)
      were significant variables (p < or = .05, multiple logistic regression) and
      constituted the weighted scoring index. A weighted scoring index of > or = 2 and
      a history of prolonged intubation predicted PGS in 95.2% of cases. A weighted
      scoring index of < or = 1 and a history of neck surgery predicted BVFP in 95.0%
      of cases. CONCLUSIONS: The weighted scoring index with the patient history
      provides an objective tool for diagnosing BVFI.

PMID- 16805376
TI  - Management of the thick-skinned nose: A more effective approach.
AB  - A bulky nose is a challenging issue to manage, and surgeons have not found the
      ultimate solution to this problem in the evolution of rhinoplastic surgery.
      Because of the multiplicity of techniques and controversies published in the
      literature, it has become confusing for the operating surgeon to find the most
      appropriate and effective way of solving this frustrating dilemma. The
      subcutaneous fat is the thickest in the supratip area, and the soft tissue
      thickness over the tip of the nose varies considerably from patient to patient.
      The focus of this study was to find a method for reducing the overlying soft
      tissue of the tip for better re-draping of skin over the nasal skeleton. The
      hallmark of this technique is to undermine the nasal skin in two layers. We
      believe that soft tissue trimming in biplane dissection can minimize the
      thickness of the tip skin in a relatively safe and homogeneous way. With this
      report we introduce a new method of dissection of nasal soft tissue and of
      trimming it in different areas of the nose for different purposes. In the
      authors' opinion, this approach is one of the most effective ways of handling
      unpliable, thick nasal skin.

PMID- 16805377
TI  - Expression profile of immune-associated genes in nasal polyps.
AB  - OBJECTIVES: We performed this study to investigate the expression profile of
      immune-associated genes and to probe the role of related genes in the immune
      pathogenesis of nasal polyps. METHODS: Microarray analysis was used to find the
      expression profile of 491 immune-associated genes in nasal polyps. In validation
      studies, immunohistochemical staining and Western blot analysis were used to
      detect interleukin (IL)-17 and IL-17 receptor (IL-17R) in nasal polyps and
      controls. RESULTS: Eighty-seven genes were differentially expressed in the immune
      associated gene profile of nasal polyps, and 15 genes showed differential
      expression in both chips. In nasal polyp tissues, IL-17 was expressed mainly in
      the cytoplasm of plasma cells and to a lesser degree in the prickle cell layer of
      the epithelium and the acinus of the serous gland. In turbinates, IL-17 was also
      expressed in the same location, but the expression of IL-17 in nasal polyps and
      that in turbinates differed significantly (p < .05). Both IL-17 and IL-17R
      displayed specific bands in nasal polyps and turbinates, but the bands of IL-17
      and IL-17R in nasal polyps were stronger than those in turbinates. CONCLUSIONS:
      The differentially expressed genes in immune-associated gene chips will provide
      clues about, and a theoretical foundation for, the pathogenesis of nasal polyps.
      Furthermore, IL-17 may play an important role in the occurrence of nasal polyps
      by overexpression.

PMID- 16805378
TI  - New method of identifying the internal auditory canal as seen from the middle
      cranial fossa approach.
AB  - OBJECTIVES: The middle cranial fossa approach allows one to remove acoustic
      tumors and preserve the facial nerve and hearing. However, there are no
      consistent landmarks on the surface of the temporal bone to identify the internal
      auditory canal. This study was designed to identify the internal auditory canal
      by use of external and internal references as seen during the middle cranial
      fossa approach. METHODS: We dissected 32 temporal bones using the middle cranial
      fossa approach and measured the distances from the posterior origin of the
      zygomatic arch to an imaginary coronal line between the foramen spinosum and the
      foramen ovale. We measured the angle between the lines drawn from the posterior
      origin of the zygomatic root to the foramen spinosum and from the foramen
      spinosum to the porus of the internal auditory canal. RESULTS: The distances were
      14.7 mm and 22.9 mm, respectively, and the angle was roughly 90 degrees.
      CONCLUSIONS: In this study, we found external and internal landmarks that help to
      locate the internal auditory canal.

PMID- 16805379
TI  - Short-duration enzymatic treatment promotes integration of a cartilage graft in a
      defect.
AB  - OBJECTIVES: Surgical manipulation of cartilage tissue is associated with
      chondrocyte death in the wound edges that hinders integration. The objective of
      this study was to evaluate the effect of a short course of treatment of a
      cartilage graft with a combination of hyaluronidase and collagenase on
      chondrocyte density and integrative capacity. METHODS: Cartilage explants were
      treated with enzymes for various time periods and at various concentrations. A
      central core was punched out of a larger explant, treated with enzymes,
      reimplanted, and placed subcutaneously in athymic mice. The number of
      chondrocytes in the wound edges was counted, and the integrative capacity of the
      grafts was evaluated by histology. RESULTS: Treatment with collagenase for 48
      hours led to a significant increase in the number of vital chondrocytes and
      restored it to normal after 14 days of culture. Treatment with hyaluronidase and
      collagenase for 48 hours further increased chondrocyte densities to supranormal
      values. Shortening the treatment to 1 hour restored the chondrocyte density to
      normal after 14 days of culture. In vivo integration experiments showed increased
      chondrocyte densities in treated wound edges and extracellular matrix fibers
      crossing over from enzyme-treated parts to untreated parts. CONCLUSIONS: Short
      duration treatment of a cartilage graft with a combination of hyaluronidase and
      collagenase increases cell density at wound edges and promotes integrative
      repair.

PMID- 16805380
TI  - Collagen subtypes in human vocal folds.
AB  - OBJECTIVES: The collagen subtypes in human vocal folds are of particular
      interest, because each collagen subtype has different features that make it
      uniquely suited for performing specific tissue tasks and each collagen subtype
      can affect the tissue properties of the vocal fold lamina propria. METHODS: Human
      vocal folds from 5 autopsy cases (less than 65 years old) were examined by
      immunohistochemistry for collagen types I, III, IV, and V and elastin. RESULTS:
      Collagen type III was distributed throughout the whole lamina propria. Type I was
      found just beneath the basal membrane, in the deep layer of the lamina propria
      and in the anterior and posterior maculae flavae. Types IV and V were present in
      the epithelial and endothelial basal membrane. Three-dimensional images from
      thick specimens reconstructed with confocal microscopy showed 2 distinct
      patterns: type III fibers were wavy, collagenous fibers, as previously observed
      in the vocal folds, and type I fibers were thinner than type III fibers. These
      results suggest that type III fibers help maintain the lamina propria structure
      and that type I fibers provide the tensile strength required around the basal
      membrane and vocal ligament to maintain the vocal fold shape while withstanding
      vibratory forces.

PMID- 16805381
TI  - Laryngotracheal stenosis repair using cartilage-derived morphogenic proteins: A
      pilot study.
AB  - OBJECTIVES: This pilot study evaluated the role of cartilage-derived morphogenic
      proteins (CDMPs) as promoters of cartilage growth and differentiation and as a
      possible alternative to autologous cartilage grafts in laryngotracheal
      reconstruction. METHODS: In phase 1, 6 New Zealand rabbits underwent
      subperichondrial injection of CDMP-1, CDMP-2, or CDMP-3 in the right thyroid ala
      and normal saline solution in the left thyroid ala as controls. In phase 2, 14
      rabbits underwent anterior cricoid split and interposition of a fibrillar
      collagen sponge saturated with normal saline solution, CDMP-2, or CDMP-3.
      RESULTS: In both phases, saline solution failed to induce new cartilage or bone
      growth. Small foci of cartilage and/or bone formation were observed within the
      thyroid subperichondria of those rabbits injected with CDMP-2 or CDMP-3. In phase
      2, a few small foci of new cartilage and/or bone formation were observed at the
      edges of the cricoid split with CDMP-2 and CDMP-3. CONCLUSIONS: A different
      carrier of CDMP, a change in dosage, or a combination of CDMPs might yield more
      significant neochondrification. The role of CDMPs as promoters of cartilage and
      differentiation could not be disqualified in this study and should be further
      investigated.

PMID- 16805382
TI  - [Membrane proteins and phospholipids as effectors of reverse cholesterol
      transport].
AB  - The review highlights the membrane aspect of cholesterol efflux from cell
      membranes to high density lipoproteins (HDL), an initial stage of reverse
      cholesterol transport to liver. Special attention is paid to ABC-A1 transporter
      and membrane SR-B1 receptor, their properties, putative mechanisms of action and
      their role in reverse cholesterol transport. Interaction of ABC-AI with plasma
      free apoA1 is suggested to facilitate the efflux of membrane phospholipids and
      formation of their complex with apoAI. Then this complex accepts the membrane
      cholesterol, with lipidation till the full HDL particle is formed. For a number
      of cells the correlation of cholesterol efflux into HDL with SR-BI expression was
      shown. The reversible binding of receptor SR-BI with HDL is supposed to influence
      molecular organization of membrane lipids, that promotes the efflux of
      cholesterol molecules out of the membrane.

PMID- 16805383
TI  - [Possible mechanism and physiopathological significance of superoxide dismutase
      regulation by oxygen free radicals].
AB  - Possible mechanism of regulation of Cu,Zn-superoxide dismutase activity by oxygen
      free radicals is considered. It consists in the increase of dissociation of
      aggregated forms of this enzyme. The increase of specific activity may have
      pathophysiological importance under conditions of oxidative stress.

PMID- 16805384
TI  - [The influence of quercetin on the activity of purified 20S, 26S proteasome and
      proteasomal activity in isolated cardiomyocytes].
AB  - For the clarification of the effect of quercetin on the proteasome experiments
      were performed using purified 20S proteasome, 26S proteasome from the proteasomal
      fraction II (PF II), as well as cardiomyocyte culture which underwent anoxia
      reoxygenation. In the experiments with purified 20S proteasome it was shown, that
      quercetin in a dose-dependent manner inhibits all three peptidase activities of
      the proteasome, comparable to a specific proteasome inhibitor. The highest
      quercetin inhibition was observed in the case of chymotrypsin-like activity of
      proteasome. In the same way quercetin inhibited the activity of 26S proteasome
      from the PF II. Quercetin decreased trypsin-like (by 26%, p = 0.03), chymotrypsin
      like (by 63.7%, p = 0.04) and peptidyl-glutamyl peptide-hydrolyzing (by 34.2%, p
      = 0.16) activities in the cardiomyocytes culture. It appears, that quercetin and
      its water-soluble analogue korvitin affect the cardiomyocytes in the same manner,
      as specific proteasome inhibitors clasto-lactacystin-beta-lactone. In the
      concentrations 5 and 10 mM quercetin and korvitin resulted in the decrease of the
      amount of living cardiomyocytes, increasing the amount of necrotic and apoptotic
      cells. In the concentration 2.5 mM quercetin and korvitin significantly abolished
      damaging effect of anoxia-reoxygenation, decreasing the amount of necrotic and
      apoptotic cells. These data suggest that the mechanisms of cardioprotective
      effect of quercetin connected with inhibition of proteasome.

PMID- 16805385
TI  - [The effect of magnesium pool isotopy on reactivation of mitochondrial ATP
      synthesis suppressed by 1-methyl-nicotine amide].
AB  - The ATP-generating activity of both rat myocardial mitochondria and
      intramitochondrial creatine phosphokinase (CPK) was examined as a function of the
      incubation medium magnesium pool isotopy. The in vitro systems tested were
      prepared from the hearts of animals treated with single injection of 1-methyl
      nicotine amide (MNA) suppressing the NAD(P)-dependent reactions in vivo. The
      presense of the 25Mg paramagnetic cations leads to essential compensation of
      intramitochondrial ATP deficiency caused by the MNA induced blockade of oxidative
      phosphorylation. This effect is merely unreachable in those systems where the
      magnesium pool consists of isotopes with a zero nuclear spin (24Mg, 26Mg). The
      reactivation of mitochondrial ATP synthesis described here involves CPK activity
      which does not depends on MNA. In this case, a high efficiency of this
      reactivation seems to be a spin selective phenomenon which requires,
      predominantly, 25Mg2+ cations.

PMID- 16805386
TI  - [The intensity of free radical oxidation and catalytic properties of the rat
      liver NADP-isocitrate dehydrogenase in the norm and in toxic hepatitis].
AB  - Parameters of hepatic free radical oxidation and catalytic properties of NADP
      isocitrate dehydrogenase (EC 1.1.1.42; NADP-IDH) have been investigated in normal
      rats and under conditions of toxic hepatitis. Development of hepatitis was
      accompanied by the increase of conjugated dienes, malondialdehyde and some
      chemiluminescence parameters. Toxic hepatitis was also accompanied by the
      increase of liver NADP-IDH. Homogenous preparations of liver NADP-IDH from normal
      and toxic rats exhibited different sensitivity to effectors studied (Fe2+, Ca2+,
      H2O2, reduced glutatione).

PMID- 16805387
TI  - [Effects of chronic administration of high doses of potassium iodide on iodine
      metabolism in the rat thyroid gland].
AB  - The effect of various doses of KI on iodine methabolism in rat thyroid gland was
      investigated. Treatment with 1, 3, 10, 100 and 500 physiological daily doses of
      KI for 14 days had no influence on blood level of thyroid hormones. However,
      increased administration of KI was accompanied by the increase of iodine in the
      thyroid gland tissue by 60-121% due to 35-108% and 94-128% increases of protein
      bound and free fractions respectively. Chronic treatment with both low and high
      doses of KI was accompanied by oxidative stress. It is suggested that reactive
      oxygen species and highly iodinated proteins (particularly thyroglobulin) induced
      by chronic ingestion of high doses of KI can play the important role in the
      development of thyroid dysfunctions and autoimmune diseases.

PMID- 16805388
TI  - [Synthesis of monoamine oxidase in subcellular structures in normal conditions
      and in alcoholism].
AB  - Seasonal variations of recovery of liver monoamine oxidase activity were studied
      in different subcellular fractions after administration of a large dose of
      pargyline in vivo. It was shown that the recovery of cytosolic MAO differs
      greatly from the membrane bound forms in the rate of reconstitution of its
      activity upon irreversible inhibition in vivo. Alcoholization leads to a decrease
      of the rate of recovery of only the membrane-bound but not a cytosolic MAO B
      forms in rat liver.

PMID- 16805389
TI  - [Modulation of reactivity of cyclic adenosine monophosphate phosphodiesterase
      under the effect of pyridinecarboxylic acid derivatives and Pt(IV) metal
      complexes on their basis].
AB  - The effect of substituted nicotinamides and isonicotinamides and Pt(IV) metal
      complexes based on the substituted nicotinamides and isonicotinamides on the
      activity of cAMP phosphodiesterase was studied. Isonicotinamide derivatives are
      efficient enzyme activators, whereas substituted nicotine amides are inhibitors
      of enzymatic cAMP phosphodiesterase activity; their inhibitory potency is
      comparable to that of theophylline used as a reference drug.

PMID- 16805390
TI  - [Cellular mechanisms of induction of apoptosis in human erythroleukaemic K562
      cells line treated by quinoline-N-oxide derivatives].
AB  - We have studied the influence of 2-(4'-nitrostyryl)-quinoline-1-oxide (2-NSQO)
      and 4-(4'-nitrostyryl)-quinoline-1-oxide (4-NSQO) on modulation activity of
      microsomal NADPH-oxidoreductases, concentration of nicotinamide enzymes and
      induction of apoptosis in human erythroleukaemic K562 cells. It was shown, that
      activity of microsomal NADPH-cytochrome c-reductases in cancer cells was
      inhibited by 10 microM 4-NSQO (15%), and 10 microM 2-NSQO (50%). Treatment of
      cells with these reagents for two days, was accompanied by caspases-9 and -3
      activation, rise of EtBr and DAPI fluorescence related to DNA binding and
      induction of apoptosis. Apoptosis was preceded by the decrease of concentration
      of nicotinamide enzymes. Thus 4-NSQO is a promising compound for further
      experimental trials as an anticancer drug with low toxic action on the tissues of
      organism.

PMID- 16805391
TI  - [The effect of carnosine on inflammatory processes during contusion of the
      eyeball].
AB  - The effect of dipeptide carnosine on proteolytic processes accompanying
      inflammation was investigated in lacrimal fluid of patients with eyeball
      contusion. Eye drops containing 5% carnosine in combination with traditional
      treatment reduced elastase-like activity in lacrimal fluid and increased
      effectiveness of therapy.

PMID- 16805392
TI  - [Changes in the lipoprotein metabolism in alcoholism do not recover during of
      prolonged remission].
AB  - Contents of lipoproteins (LP), activity of lipoprotein lipase (LP-lipase) and
      cholesterol esterification activity of blood serum were examined in patients with
      alcoholism at the periods of intoxication, alcohol abstinence and under
      conditions of prolonged remission. During remission a general pattern of apoB
      containing LP was similar to the period of intoxication. Processes of
      transformation of this class LP significantly delayed in isolated blood serum in
      vitro. The magnitude of these changes almost corresponded to the period of
      intoxication. However activity of free and membrane-bound forms of LP-lipase. A
      high level of LPHD2a was characteristic for the conditions of intoxication and
      alcohol abstinence. In the remission the level of all the apoA-containing LP
      fractions was significantly lower than in the control. Besides, processes of
      their transformations in vitro were slowed down. Intensity of these changes
      resembled the period of intoxication. Thus, disorders of LP metabolism pointed
      out during the period of intoxication and alcohol abstinence do not recovered
      under conditions of a prolonged remission.

PMID- 16805393
TI  - [Isoelectrofocusing and photocolorimetry for determination of glycated hemoglobin
      (HbA1c)].
AB  - Analytical reliability of a new method for determination of glycated hemoglobin
      (HbA1c) has been evaluated. The method is based on hemoglobin isolation during
      isoelectrofocusing followed by acidic hydrolysis and photocolorimetry of furfurol
      formed after its reaction with thiobarbituric acid. At diabetic and non-diabetic
      levels inter- and intraserial reproducibility varied from 6 to 21%. Sensitivity
      of this method was determined using physiological solution and 50% albumin.

PMID- 16805394
TI  - [Testing of the antioxidant activity of substances using gasometric method of
      determination of egg yolk lipoproteins oxidation].
AB  - The gasometric method of iron-initiated oxidation of egg yolk lipoproteins has
      been employed for analysis of antioxidant activity. The optimal conditions of
      oxidation providing reproducible results on the kinetics process have been
      chosen. The antioxidant concentration required for 50% decrease of oxygen
      consumption is proposed as the parameter characterizing antioxidant activity of
      the compounds studied. The influence of different factors on effectiveness of
      inhibition of lipid peroxidation by phenolic antioxidants was analyzed.

PMID- 16805395
TI  - [Diagnostic and prognostic value of antioxidant enzyme assay in erythrocytes of
      patients with end stage renal disease treated with hemodialysis].
AB  - Anemia is one of the main complications seen in patients with end stage renal
      disease (ESRD) treated with hemodialysis. We hypothesized that oxidative stress
      and decrease of antioxidant defense enzyme activity may be major causes
      underlying functional insufficiency of erythrocytes. Blood samples of 16 patients
      with ESRD undergoing hemodialysis were investigated. All patients received
      Recormon for treatment of anemia. In spite of effective hemodialysis procedures
      cleared patient blood the erythrocyte activities of superoxide dismutase (SOD),
      glutathione peroxidase (GP) were lower than in healthy controls and hemodialysis
      procedure insignificantly influenced enzyme activities. After 6 months repeated
      study of the erythrocyte enzymes revealed further decrease of SOD and GP
      activities.

PMID- 16805396
TI  - Health effects of fine particulate air pollution: lines that connect.

PMID- 16805397
TI  - Health effects of fine particulate air pollution: lines that connect.
AB  - Efforts to understand and mitigate thehealth effects of particulate matter (PM)
      air pollutionhave a rich and interesting history. This review focuseson six
      substantial lines of research that have been pursued since 1997 that have helped
      elucidate our understanding about the effects of PM on human health. There
      hasbeen substantial progress in the evaluation of PM health effects at different
      time-scales of exposure and in the exploration of the shape of the concentration
      response function. There has also been emerging evidence of PM-related
      cardiovascular health effects and growing knowledge regarding interconnected
      general pathophysiological pathways that link PM exposure with cardiopulmonary
      morbidiity and mortality. Despite important gaps in scientific knowledge and
      continued reasons for some skepticism, a comprehensive evaluation of the research
      findings provides persuasive evidence that exposure to fine particulate air
      pollution has adverse effects on cardiopulmonaryhealth. Although much of this
      research has been motivated by environmental public health policy, these results
      have important scientific, medical, and public health implications that are
      broader than debates over legally mandated air quality standards.

PMID- 16805398
TI  - Modeling atmospheric mercury deposition in the vicinity of power plants.
AB  - Two mathematical models of the atmospheric fate and transport of mercury (Hg), an
      Eulerian grid-based model and a Gaussian plume model, are used to calculate the
      atmospheric deposition of Hg in the vicinity (i.e., within 50 km) of five coal
      fired power plants. The former is applied using two different horizontal
      resolutions: coarse (84 km) and fine (16.7 km). More than 96% of the power plant
      Hg emissions are calculated with the plume model to be transported beyond 50 km
      from the plants. The grid-based model predicts a lower fraction to be transported
      beyond 50 km: >91% with a coarse resolution and >95% with a fine resolution. The
      contribution of the power plant emissions to total Hg deposition within a radius
      of 50 km from the plants is calculated to be <8% with the plume model, <14% with
      the Eulerian model with a coarse resolution, and <10% with the Eulerian model
      with a fine resolution. The Eulerian grid-based model predicts greater local
      impacts than the plume model because of artificially enhanced vertical
      dispersion; the former predicts about twice as much Hg deposition as the latter
      when the area considered is commensurate with the resolution of the grid-based
      model. If one compares the local impacts for an area that is significantly less
      than the grid-based model resolution, then the grid-based model may predict lower
      local deposition than the plume model, because two compensating errors affect the
      results obtained with the grid-based model: initial dilution of the power plant
      emissions within one or more grid cells and enhanced vertical mixing to the
      ground.

PMID- 16805399
TI  - Characterization of polycyclic aromatic hydrocarbons from the diesel engine by
      adding light cycle oil to premium diesel fuel.
AB  - Diesel fuels governed by U.S. regulations are based on the index of the total
      aromatic contents. Three diesel fuels, containing various fractions of light
      cycle oil (LCO) and various sulfur, total polyaromatic, and total aromatic
      contents, were used in a heavy-duty diesel engine (HDDE) under transient cycle
      test to assess the feasibility of using current indices in managing the emissions
      of polycyclic aromatic hydrocarbons (PAHs) from HDDE. The mean sulfur content in
      LCO is 20.8 times as much as that of premium diesel fuel (PDF). The mean total
      polyaromatic content in LCO is 28.7 times as much as that of PDF, and the mean
      total aromatic content in LCO is 2.53 times as much as that of PDF. The total
      polyaromatic hydrocarbon emission factors in the exhaust from the diesel engine,
      as determined using PDF L3.5 (3.5% LCO and 96.5% PDF), L7.5 (7.5% LCO and 92.5%
      PDF), and L15 (15% LCO and 85% PDF) were 14.3, 25.8, 44, and 101 mg L(-1),
      respectively. The total benzo(a)pyrene equivalent (BaPeq) emission factors in the
      exhaust from PDF, L3.5, L7.5, and L15 were 0.0402, 0.121, 0.219, and 0.548 mg L(
      1), respectively. Results indicated that using L3.5 instead of PDF will result in
      an 80.4% and a 201% increase of emission for total PAHs and total BaPeq,
      respectively. The relationships between the total polyaromatic hydrocarbon
      emission factor and the two emission control indices, including fuel polyaromatic
      content and fuel aromatic content, suggest that both indices could be used
      feasibly to regulate total PAH emissions. These results strongly suggest that LCO
      used in the traveling diesel vehicles significantly influences PAH emissions.

PMID- 16805400
TI  - Mass transfer within electrostatic precipitators: trace gas adsorption by sorbent
      covered plate electrodes.
AB  - Varying degrees of mercury (Hg) capture have been reported within the
      electrostatic precipitators (ESPs) of coal-fired electric utility boilers. There
      has been some speculation that the adsorption takes place on the particulate
      covered plate electrodes. This convective mass transfer analysis of laminar and
      turbulent channel flows provides the maximum potential for Hg adsorption by the
      plate electrodes within an ESP under those conditions. Mass transfer
      calculations, neglecting electrohydrodynamic (EHD) effects, reveal 65% removal of
      elemental Hg for a laminar flow within a 15-m-long channel of 0.2-m spacing and
      42% removal for turbulent flow within a similar configuration. Both
      configurations represent specific collection areas (SCAs) that are significantly
      larger than conventional ESPs in use. Results reflecting more representative SCA
      values generally returned removal efficiencies of <20%. EHD effects, although
      potentially substantial at low Reynolds numbers, diminish rapidly with increasing
      Reynolds number and become negligible at typical ESP operating conditions. The
      present results indicate maximum Hg removal efficiencies for ESPs that are much
      less than those observed in practice for comparable ESP operating conditions.
      Considering Hg adsorption kinetics and finite sorbent capacity in addition to the
      present mass transfer analyses would yield even lower adsorption efficiencies
      than the present results. In a subsequent paper, the author addresses the mass
      transfer potential presented by the charged, suspended particulates during their
      collection within an ESP and the role they potentially play in Hg capture within
      ESPs.

PMID- 16805401
TI  - Degradation of gas-phase propylene glycol monomethyl ether acetate by
      ultraviolet/ozone process: A kinetic study.
AB  - A pilot-scale plug-flow reactor was built to investigate its performance in
      treating airborne propylene glycol monomethyl ether acetate (PGMEA) via
      ozonation, ultraviolet (UV) photolysis and UV/O3 technologies. Governing factors,
      such as the initial molar ratio of ozone (O3) to PG-MEA, UV volumetric electric
      power input, and moisture content in the influent airstream, were investigated. A
      1-L batch reactor was used to investigate some photodegradation characteristics
      of PGMEA in advance. Experiments were conducted at a fixed influent PGMEA
      concentration of approximately 50 ppm and an ambient temperature of 26 degrees C.
      A gas space time of 85 sec in the plug-flow reactor was kept for either ozonation
      or photolysis reaction, whereas a gas space time of 170 sec was used for the
      UV/O3 degradation. Results show that an initial molar ratio of O3 to PGMEA of
      >2.91 and an UV volumetric electric input power of 0.294 W/L(-1) sufficed to
      obtain PGMEA decompositions of >90% by UV/O3. Kinetic analyses indicate that all
      types of PGMEA decomposition are pseudo-first order with respect to its
      concentration. Moisture content (relative humidity = 15-99%) and UV volumetric
      electric input power (0.147 and 0.294 W/L(-1)) were major factors that strongly
      affect the PGMEA degradation rate.

PMID- 16805402
TI  - Road grade estimation for on-road vehicle emissions modeling using light
      detection and ranging data.
AB  - Vehicle-specific power (VSP) is useful for explaining a substantial portion of
      variability in real-world vehicle emissions, such as those measured with portable
      emissions monitoring systems (PEMS). VSP is a function of vehicle speed,
      acceleration, and road grade. Road grade is shown to significantly affect
      estimates of both VSP and of real-world emissions via sensitivity analysis and
      analysis of empirical data. However, road grade is difficult to measure reliably
      using PEMS. Therefore, alternative methods for estimating road grade were
      identified and compared. A preferred method for estimating road grade was
      explored in more detail based on light detection and ranging (LIDAR) data. The
      method includes buffering LIDAR data onto roadway maps using a geographic
      information system tool, defining segments of roadway based on criteria
      pertaining to vertical curvature, quantification of roadway elevations within the
      buffered segments, and estimation of road grade and banking by fitting a plane to
      each segment. Factors influencing errors in road grade estimates are discussed.
      The method was evaluated by application to selected interstate highways and
      comparison to design drawing data. The development and application of LIDAR-based
      road grade data are demonstrated via a case study using PEMS data collected in
      the Research Triangle Park, NC, area. LIDAR data are shown to be reliable and
      accurate for road grade estimation for vehicle emissions modeling.

PMID- 16805403
TI  - An inexpensive dual-chamber particle monitor: laboratory characterization.
AB  - In developing countries, high levels of particle pollution from the use of coal
      and biomass fuels for household cooking and heating are a major cause of ill
      health and premature mortality. The cost and complexity of existing monitoring
      equipment, combined with the need to sample many locations, make routine
      quantification of household particle pollution levels difficult. Recent advances
      in technology, however, have enabled the development of a small, portable, data
      logging particle monitor modified from commercial smoke alarm technology that can
      meet the needs of surveys in the developing world at reasonable cost. Laboratory
      comparisons of a prototype particle monitor developed at the University of
      California at Berkeley (UCB) with gravimetric filters, a tapered element
      oscillating microbalance, and a TSI DustTrak to quantify the UCB particle monitor
      response as a function of both concentration and particle size and to examine
      sensor response in relation to changes in temperature, relative humidity, and
      elevation are presented here. UCB particle monitors showed good linearity in
      response to different concentrations of laboratory-generated oleic acid aerosols
      with a coarse (mass median diameter, 2.1 microm) and fine (mass median diameter,
      0.27-0.42 microm) size distributions (average r2 = 0.997 +/- 0.005). The
      photoelectric and ionization chamber showed a wide range of responses based on
      particle size and, thus, require calibration with the aerosol of interest. The
      ionization chamber was five times more sensitive to fine rather than coarse
      particles, whereas the photoelectric chamber was five times more sensitive to
      coarse than fine. The ratio of the response between the two sensors has the
      potential for mass calibration of individual data points based on estimated
      parameters of the size distribution. The results demonstrate the significant
      potential of this monitor, which will facilitate the evaluation of interventions
      (improved fuels, stoves, and ventilation) on indoor air pollution levels and
      research on the impacts of indoor particle levels on health in developing
      countries.

PMID- 16805404
TI  - Conjunctive use of models to design cost-effective ozone control strategies.
AB  - The management of tropospheric ozone (O3) is particularly difficult. The
      formulation of emission control strategies requires considerable information
      including: (1) emission inventories, (2) available control technologies, (3)
      meteorological data for critical design episodes, and (4) computer models that
      simulate atmospheric transport and chemistry. The simultaneous consideration of
      this information during control strategy design can be exceedingly difficult for
      a decision-maker. Traditional management approaches do not explicitly address
      cost minimization. This study presents a new approach for designing air quality
      management strategies; a simple air quality model is used conjunctively with a
      complex air quality model to obtain low-cost management strategies. A simple air
      quality model is used to identify potentially good solutions, and two heuristic
      methods are used to identify cost-effective control strategies using only a small
      number of simple air quality model simulations. Subsequently, the resulting
      strategies are verified and refined using a complex air quality model. The use of
      this approach may greatly reduce the number of complex air quality model runs
      that are required. An important component of this heuristic design framework is
      the use of the simple air quality model as a screening and exploratory tool. To
      achieve similar results with the simple and complex air

PMID- 16805405
TI  - Removal of SO2 from simulated flue gases using non-thermal plasma-based microgap
      discharge.
AB  - The removal of sulfur dioxide (SO2) from simulated flue gases streams
      (N2/O2/H2O/SO2) was experimentally investigated using microgap discharge. In the
      experiment, the thinner dielectric layers of aluminum oxide (Al2O3) were used to
      form the microgap discharge. With this physical method, a high concentration of
      hydroxyl (OH*) radicals were produced using the ionization of O2 and H2O to
      further the conversion of SO2 into sulfuric acid (H2SO4) at 120 degrees C in the
      absence of any catalysts and absorbents, which were captured with the
      electrostatic precipitator (ESP). As a result, the increase of discharge power
      and concentrations of O2 and H2O increased the production of OH. radicals
      resulting in enhanced removal of SO2 from gas streams. With the test and
      analysis, a number of H2SO4 droplets were produced in experiment. Therefore, a
      new method for removal of SO2 in semidry method without ammonia (NH3) additive
      was found.

PMID- 16805406
TI  - Improving environmental risk management through historical impact assessments.
AB  - A historical contaminant impact assessment was conducted at 48 heavy
      manufacturing facilities located in 20 different states for a U.S.-based company.
      The facilities evaluated were industrial manufacturing sites that operated for as
      long as 100 yr and used several types of hazardous substances, including solvents
      and degreasers, oils and other petroleum products, paints and pigments, and heavy
      metals. The purpose of conducting the impact assessment was to provide direction
      and guidance on future environmental objectives and pollution prevention
      initiatives. The impact assessment involved examining historical investigative
      and remediation costs since 1985, types of contaminants, subsurface geology,
      hydrology, and regulatory requirements. The results reveled that 85% of the
      historical environmental costs were associated with hexavalent chromium and
      chlorinated solvents. Other contaminants, such as oils and other petroleum
      products and other heavy metals, were far more commonly detected but only
      accounted for the remaining 15% of costs. The results also indicated that the
      costs are also strongly associated with the type of geologic environment to which
      the chemicals were released. As a result of these findings, an aggressive
      pollution prevention program has been initiated to eliminate the use of those
      contaminants that are especially expensive to remediate and to develop stronger
      and more effective engineering controls at facilities located in sensitive
      ecological areas.

PMID- 16805407
TI  - Mapping and profile of emission sources for airborne volatile organic compounds
      from process regions at a petrochemical plant in Kaohsiung, Taiwan.
AB  - This work surveyed five process regions inside a petrochemical plant in Taiwan to
      characterize the profiles of airborne volatile organic compounds (VOCs) and
      locate emission sources. Samples, taken with canisters, were analyzed with gas
      chromatography-mass spectrometry according to the TO-14 method. Each region was
      deployed with 24 sampling sites, sampled twice, and 240 samples in total were
      measured during the survey period. All of the data were consolidated into a
      database on Excel to facilitate retrieval, statistical analysis, and presentation
      in the form of a table or graph, and, subsequently, the profile of VOCs was
      elucidated. Emission sources were located by mapping the concentration
      distribution of either an individual or a type of species in terms of contour
      maps on Surfer. Through the cross-analysis of data, the abundant VOCs included
      alkenes, dienes, alkanes, and aromatics. A total of 19 emission sources were
      located from these five regions. The sources for alkanes stood inside first,
      third aromatic, and fourth naphtha cracking regions, whereas the ones for alkenes
      were inside two naphtha cracking regions. The sources for dienes were found
      inside the third naphtha cracking region alone; in contrast, the sources for
      aromatics were universally traced except inside the third naphtha cracking
      region. The measured intensity for sources mostly ranged from 1000 to 7000 ppb.

PMID- 16805408
TI  - Direct field observation of the relative humidity effect on the beta-gauge
      readings.
AB  - The effect of ambient relative humidity (RH) on hourly particulate matter (PM10)
      readings of beta-gauge monitors has been studied using two collocated monitors in
      the field. The inlet air of monitor 1 was conditioned with water vapor to
      increase its RH, whereas monitor 2 operated normally in ambient conditions.
      Experimental data showed that PM10 readings of monitor 1 were nearly the same as
      monitor 2, as long as the RH of its conditioned incoming air did not exceed
      approximately 80-85%. However, when the RH exceeded approximately 80-85%, PM10
      readings of monitor 1 became higher than monitor 2, and the difference increased
      with increasing RH. The measurement of pressure drop across the filter was also
      conducted, and the data revealed that the increase of pressure drop per unit of
      PM10 concentration decreased when RH was higher than approximately 80-85%, as
      compared with the case when RH was lower than 80-85%. This is perhaps because of
      more porous structure of deposited particles in the beta-gauge monitor when RH is
      greater than approximately 80-85%. The theoretical calculation using an
      evaporation model and a thermodynamic model has been conducted to simulate the
      beta-gauge readings. The results show that the theoretical PM10 concentrations
      using the evaporation model are in better agreement with the actual beta-gauge
      readings than those using the thermodynamic equilibrium model.

PMID- 16805409
TI  - An environmental decision framework applied to marine engine control
      technologies.
AB  - This paper develops a decision framework for considering emission control
      technologies on marine engines, informed by standard decision theory, with an
      open structure that may be adapted by operators with specific vessel and
      technology attributes different from those provided here. Attributes relate
      objectives important to choosing control technologies with specific alternatives
      that may meet several of the objectives differently. The transparent framework
      enables multiple stakeholders to understand how different subjective judgments
      and varying attribute properties may result in different technology choices.
      Standard scoring techniques ensure that attributes are not biased by subjective
      scoring and that weights are the primary quantitative input where subjective
      preferences are exercised. An expected value decision structure is adopted that
      considers probabilities (likelihood) that a given alternative can meet its
      claims; alternative decision criteria are discussed. Capital and annual costs are
      combined using a net present value approach. An iterative approach is advocated
      that allows for screening and disqualifying alternatives that do not meet minimum
      conditions for acceptance, such as engine warranty or U.S. Coast Guard
      requirements. This decision framework assists vessel operators in considering
      explicitly important attributes and in representing choices clearly to other
      stakeholders concerned about reducing air pollution from vessels. This general
      decision structure may also be applied similarly to other environmental controls
      in marine applications.

PMID- 16805410
TI  - Prediction for energy content of Taiwan municipal solid waste using multilayer
      perceptron neural networks.
AB  - In the past decade, the treatment amount of municipal solid waste (MSW) by
      incineration has increased significantly in Taiwan. By year 2008, approximately
      70% of the total MSW generated will be incinerated. The energy content (usually
      expressed by lower heating value [LHV]) of MSW is an important parameter for the
      selection of incinerator capacity. In this work, wastes from 55 sampling sites,
      including villages, towns, cities, and remote islands in the Taiwan area, were
      sampled and analyzed once a season from April 2002 to March 2003 to determine the
      waste characteristics. The LHV of MSW in Taiwan was predicted by the multilayer
      perceptron (MLP) neural networks model using the input parameters of elemental
      analysis and dry- or wet-base physical compositions. Although all three of the
      models predicted LHV values rather accurately, the elemental analysis model
      provided the most accurate prediction of LHV values. Additionally, the wet-base
      physical composition model was the easiest and most economical. Therefore, the
      waste treatment operators can choose the more appropriate analysis method
      considering situations themselves, such as time, equipment, technology, and cost.

PMID- 16805411
TI  - Selected ion chromatograms and tandem mass spectrometry for detection of trace
      polycyclic aromatic hydrocarbons in diesel exhaust.
AB  - Polycyclic aromatic hydrocarbon (PAH) measurements are essential for scientists
      and engineers who investigate these anthropogenic compounds. Diesel engines
      contribute to the problem, so analysts are measuring PAHs from these sources.
      However, diesel exhaust presents special problems for precise analytical
      measurements. The exhaust matrix is very complex; consequently, PAH detection
      sensitivity deteriorates, especially for trace PAHs in the exhaust. Yet, these
      are conditions and amounts that exist in real samples. Nonetheless, selected ion
      chromatogram (SIC) and tandem mass spectrometry (MS/MS) techniques improve trace
      PAH detection; ion trap technology makes both mass techniques possible. The
      purpose of this investigation was to evaluate SIC and MS/MS for applications to
      measure PAHs in diesel exhaust samples. The signal-to-noise ratio for accurate
      quantitation improves, relative to traditional mass techniques, because these
      techniques ignore or eliminate interfering components. On a VF-5MS
      chromatographic column, these techniques improve sensitivity and reproducibility.
      They produce a superior limit of detection in the useful range for PAH samples
      extracted from actual engine exhaust, 10-30 pg for the smaller PAHs and 1-6 ng
      for the larger PAHs. The results with SIC and MS/MS are reproducible, so analysts
      can report PAH amounts with defined statistical confidence intervals. SIC and
      MS/MS improve detection for trace PAHs in convoluted diesel exhaust samples.

PMID- 16805412
TI  - Mechanisms of NOx removal from flue gas by zero valent iron.
AB  - Chemical reaction between nitric oxide (NO) andzero valent iron (ZVI) was studied
      in a packed-bed column process with high temperatures based on ZVI strong
      reducing abilities. For six controlled temperatures of 523-773 K and 400 ppm of
      NO (typical flue gas temperature and concentration), under short empty bed
      contacttime ([EBCT] 0.0226-0.0679 sec), NO was completely removed for temperature
      of 573-773 K but not for 523 K. Break-through curves were conducted for the five
      working temperatures, and the results indicated that NO reductions by ZVI were
      varied from 2 to 26.7 mg NO/g ZVI. Higher temperature and longer EBCT achieved
      better NO removal efficiency. X-ray diffraction (XRD) and electron spectroscopy
      for chemical analysis (ESCA) were conducted to analyze the crystal structure and
      oxidation state of the reacted ZVI. Three layers of iron species were detected by
      XRD: ZVI, Fe3O4, and Fe2O3. ZVI was the most prevalent species, and Fe3O4 and
      Fe2O3 were less from the XRD analysis. By ESCA, the oxidation state on the
      reacted ZVI surface was determined, and the species was identifled as Fe2O3,
      which is the most oxidizing species for iron. Therefore, three layers from the
      ZVI core to the ZVI surface can be identified: ZVI, Fe3O4, and Fe2O3. Combining
      the results from XRD and ESCA, the mechanisms for ZVI and NO can be proposed as
      two consecutive reactions from lower oxidation state (ZVI) in the core to higher
      oxidation state on the iron surface (Fe2O3): 3Fe + 4NO<--(high temperature)-
      >Fe3O4 + 2N2 (A1), 4Fe3O4 + 2NO<--(high temperature)-->6Fe2O3 + N2* (A2) Because
      there was only <5% ZVI used to remove NO comparing to theoretical ZVI used based
      on the proposed stoichiometry, it can be concluded that the heterogeneous
      reaction only occurred on the ZVI surface instead of on bulk of the ZVI.

PMID- 16805413
TI  - Effects of instrument precision and spatial variability on the assessment of the
      temporal variation of ambient air pollution in Atlanta, Georgia.
AB  - Data from the U.S. Environmental Protection Agency Air Quality System, the
      Southeastern Aerosol Research and Characterization database, and the Assessment
      of Spatial Aerosol Composition in Atlanta database for 1999 through 2002 have
      been used to characterize error associated with instrument precision and spatial
      variability on the assessment of the temporal variation of ambient air pollution
      in Atlanta, GA. These data are being used in time series epidemiologic studies in
      which associations of acute respiratory and cardiovascular health outcomes and
      daily ambient air pollutant levels are assessed. Modified semivariograms are used
      to quantify the effects of instrument precision and spatial variability on the
      assessment of daily metrics of ambient gaseous pollutants (SO2, CO, NOx, and O3)
      and fine particulate matter ([PM2.5] PM2.5 mass, sulfate, nitrate, ammonium,
      elemental carbon [EC], and organic carbon [OC]). Variation because of instrument
      imprecision represented 7-40% of the temporal variation in the daily pollutant
      measures and was largest for the PM2.5 EC and OC. Spatial variability was
      greatest for primary pollutants (SO2, CO, NOx, and EC). Population-weighted
      variation in daily ambient air pollutant levels because of both instrument
      imprecision and spatial variability ranged from 20% of the temporal variation for
      O3 to 70% of the temporal variation for SO2 and EC. Wind

PMID- 16805414
TI  - Does hospitalization for asthma and allergic diseases occur more frequently in
      Ramadan fasting: a population based study (2000-2004).
AB  - OBJECTIVE: Over one billion Muslims fast worldwide during the month of Ramadan.
      Fasting during Ramadan is a radical change in life style for the period of a
      lunar month. Our objective in this study was to investigate whether Ramadan
      fasting has any effect on the incidence of asthma and to assess whether Ramadan
      Fasting affected normal lung function values. DESIGN: This is a hospital-based
      cohort study. SETTING: Hamad General Hospital, Hamad Medical Corporation, Doha,
      State of Qatar. PATIENTS: We prospectively reviewed 1590 asthmatic Muslim
      patients who were hospitalized with asthma over a four year period from January
      2000 to December 2004. Patients were divided according to the time of
      presentation in relation to the month of Ramadan, one month before, during and
      one month after Ramadan. METHODS: Pulmonary function tests were performed on an
      electronic spirometer (Compact Vitalograph, Buckingham, U.K.). Performance of the
      spirometric test and data collection were according to as described by the
      American Thoracic Society. RESULTS: There were 1590 patients studied. Among them,
      901 were males (56.7%) and 689 were females (43.3%). Their mean age was 30 years
      (15-60). All patients expressed clinical allergy, 454 patients (28.6%) had asthma
      and rhinitis, 513 patients (32.3%) had allergic rhinitis, 300 patients (18.9%)
      had asthma alone and 10.6% had other allergic conditions. The ventilatory
      capacity of lung function parameters mean did not show any statistically
      significant differences between a period of pre-Ramadan, during Ramadan and after
      Ramadan concerning FVC, FEV1, FEF(25-75) FEV1/FVC, and PEF values. CONCLUSION:
      This study demonstrated that no significant difference was found in number of
      hospitalization and the mean spirometric values for asthma while fasting during
      the month of Ramadan when compared to the non-fasting months.

PMID- 16805415
TI  - Natural course of sensitization to hen's egg in children not previously exposed
      to egg ingestion.
AB  - BACKGROUND: Clinical adverse reactions to egg may occur in infants or children
      who have never eaten egg. They may be sensitized or even react at first egg
      ingestion. Few studies are available concerning the reality of egg white allergy
      in such sensitized children, the natural evolution of this condition and the
      appropriate decisions to make. OBJECTIVES: To analyze the actuality and natural
      course of egg allergy in children sensitized without previous of hen's egg
      ingestion. METHODS: We set up a clinical decision tree based on clinical history
      and specific egg white IgE to manage patients who had never ingested egg but were
      sensitized as demonstrated by a positive SPT and report a cohort of 30 such
      children RESULTS: The mean level of egg white specific IgE at first analysis,
      i.e. before 12 months, was high, 28.3 KU(A) /L, with a large range, from 0.6 to
      >100 KU(A) /L, below 6 KU(A) /L in only 8 patients. In 6 children ("no challenge"
      group), IgE values remained >8 KU(A) /L by the end of the survey and the oral
      challenge with egg was always denied. Their mean + SD IgE level was at 51.7 + 38
      KU(A) /L at 1 year and 19.7 + 13 KU(A) /L at a mean age of 34 + 5 months. All had
      an associated anaphylactic reaction with milk and 5 were still allergic to milk
      by the end of the survey. In the remaining 24 infants, egg was given for the
      first time at a mean age of 30 + 9 months, by error in 4 cases, all exhibiting an
      immediate reaction, and in a hospital setting in 20, among whom 14 reacted. Among
      those 18, with a specific IgE level at 9.1 + 10 KU(A) /L at 28 + 9 months, 4
      became tolerant between 3 and 4 years, with specific IgE levels below 1.3 KU(A)
      /L and a 5th one with specific IgE >100 KU(A) /L at 6 months tolerated scrambled
      eggs at age 7 year, with specific IgE at 2.6 KU(A) /L. In the 6 others, labeled
      "non allergic", egg white specific IgE levels were significantly lower, whatever
      the age, than in the "no challenge" group. The age at challenge was 35 + 8
      months, with a mean specific IgE level at 1.0 + 0.9 KU(A) /L. CONCLUSION: In
      children sensitized to egg without previous ingestion of that food, egg tolerance
      appears probably in some by the age of 3 but may reveal much more prolonged in a
      limited number.

PMID- 16805416
TI  - Peach fuzz contains large amounts of lipid transfer protein: is this the cause of
      the high prevalence of sensitization to LTP in Mediterranean countries?
AB  - BACKGROUND: Allergy to lipid transfer protein (LTP) is quite common in the
      Mediterranean countries but virtually absent in Northern Europe. The reasons for
      this latitude-dependent distribution are unclear. One hypothesis is that peach,
      the primary sensitizer to LTP, may lose in part its allergenicity as a
      consequence of treatments (handling, brushing, washing, and packaging) preceding
      marketing in Northern European. Peach surface fuzz might represent a potential
      vehicle of LTP. OBJECTIVE: To detect LTP in peach fuzz, and compare IgE
      reactivity to peach fuzz and peel of sera from LTP-allergic patients. METHODS:
      IgE reactivity to peach peel and peach fuzz extract was measured by ELISA using
      sera from 2 LTP-allergic PATIENTS. Purified peach LTP was used in inhibition
      studies. RESULTS: Both sera strongly reacted both to peach peel and fuzz but
      reactivity to fuzz was stronger than to peel. Pre-absorption of one serum with
      peach LTP caused an 87% reduction of IgE reactivity to peach fuzz extract.
      CONCLUSION: Peach fuzz contains large amounts of LTP and might be a potential
      vehicle of this allergen causing sensitization in genetically predisposed
      subjects. Fuzz loss during pre-marketing handling of peaches might be at the
      basis of the geographic differences that characterize allergy to LTP.

PMID- 16805417
TI  - Effect of immunotherapy on fungal allergy: a case report.
AB  - Candida is presented. Systemic immunotherapy with a Tricophyton/Candida vaccin
      was completely cleared the urticaria/angioedema and decreased specific IgE from
      more than 100 KUA/I to 7.6 to Tricophyton and from 4.5 KUA/I to 0.7 KUA to
      Candida after immunotherapy.

PMID- 16805418
TI  - Collagenous colitis: possible link with isotretinoin.
AB  - A case of collagenous colitis in a young man treated by isotretinoin raises the
      hypothesis of an isotretinoin inducedcess on the oossible account of atoov and
      auto-immunity in the family.

PMID- 16805419
TI  - Risk of allergy to food proteins in topical medicinal agents and cosmetics.
AB  - The risk of allergy to food proteins in cosmetics and topical medicinal agents is
      poorly evaluated. IgE dependent contact urticaria and contact dermatitis are
      observed. Eleven cases (7 infants and 4 women) are reported. Wheat, egg, oats,
      milk, peanut proteins are incriminated by prick-tests or atopy patch-tests. Cases
      are related to a previous food allergy and other ones may indicate primary
      sensitization to topical creams mainly used for skin care of atopic dermatitis. A
      consecutive exercise induced anaphylaxis to wheat and a long lasting
      sensitization to wheat have been observed. A clear and accurate identification of
      food allergens in cosmetics and topical agents is necessary. Given the hyper
      permeability of infant skin, topical products containing food proteins of known
      allergenicity are contra-indicated for neonates, and for infants with atopic
      dermatitis, which may be associated with skin hyper-permeability.

PMID- 16805420
TI  - A brief look at glial cells.
AB  - Glial cells are numerically the dominant cell type in the central and peripheral
      nervous system. They are intermixed with the nerve cells and are found in
      intimate contacts with neuronal cell bodies, dendrites, axons and synaptic
      contacts. Like neurons, glial cells are a heterogeneous population of cells that
      differ in developmental origin, molecular composition, structure and activity.
      When these cells were first discovered some 150 years ago they were viewed as a
      type of connective tissue support for nerve cells. They are now known to be
      essential for the development and function of the brain and other parts of the
      nervous system. They are also central players in a large number of pathological
      processes. We have therefore moved away from a view of the nervous system as a
      system of neurons, to the appreciation that it is a neural system where the
      contributions of both nerve and glial cells are intimately integrated,
      interdependent and obligatory.

PMID- 16805421
TI  - The acquisition of myelin: a success story.
AB  - The myelin sheath, and hence the myelin-forming cells (i.e. Schwann cells in the
      PNS and oligodendrocytes in the CNS), have been a crucial acquisition of
      vertebrates. The major function of myelin is to increase the velocity of
      propagation of nerve impulses. Invertebrate axons are ensheathed by glial cells,
      but do not have a compact myelin. As a consequence, action potentials along
      invertebrate axons propagate at about 1 m/s, or less. This is sufficient,
      however, for the survival of small animals (between 0.1 and 30cm). Among
      invertebrates, only the cephalopods are larger. By increasing their axonal
      diameter to 1 mm or more, cephalopods have been able to increase the speed of
      propagation of action potentials and therefore adapt nerve conduction to their
      larger body size. However, due to the physical constraint imposed by the skull
      and vertebrae, vertebrates had to find an alternative solution. This was achieved
      by introducing the myelin sheath, which leads action potentials to propagate at
      speeds of 50-100m/s without increasing the diameter of their axons. Not all
      vertebrate axons, however, are myelinated. In the protovertebrates (lancelets,
      hagfishes, lampreys), which belong to the agnathes (jawless fishes), axons are
      not ensheathed by myelin. Among living vertebrates, the most ancient myelinated
      species are the cartilaginous fishes (sharks, rays), suggesting that acquisition
      of myelin is concomitant with the acquisition of a hinged-jaw, i.e. the
      gnathostoma. The close association between the apparition of a hinged-jaw and the
      myelin sheath has led to speculation that among the devonian fishes that have
      disappeared today, the jawless conodonts and ostracoderms were not myelinated,
      and that myelin was first acquired by the oldest gnathostomes: the placoderms. I
      also question where myelin first appeared: the PNS, the CNS or both? I provide
      evidence that, in fact, it is not the type of myelin-forming cell that is
      crucial, but the appearance of axonal signals, rendering axons receptive to
      inducing an ensheathing glial cell to wrap around the axon. Under certain
      circumstances or in some species, invertebrate ensheathing glial cells wrap
      around axon to form a pseudo-myelin sheath. Therefore, to form myelin it was not
      compulsory to 'invent' a new cell type. Hence my conclusion that myelination has
      most probably started simultaneously in the PNS and the CNS, using pre-existing
      ensheathing glial cells.

PMID- 16805422
TI  - Purinergic signalling--an overview.
AB  - A brief account of the early history of extracellular signalling by ATP will be
      followed by a summary of the current subclassification of receptors for purines
      and pyrimidines. On the basis of cloning, transduction mechanisms and
      pharmacology, the P1 (adenosine) receptor family has 4 subtypes, while the P2
      (ATP, ADP and UTP) receptor family has been divided into P2X ionotropic receptors
      (7 subtypes) and P2Y metabotropic G protein-coupled receptors (8 subtypes). The
      distribution of purinoceptors in both neuronal and non-neuronal cells and the
      physiology and pathophysiology of purinergic signalling will be reviewed.
      Examples of fast purinergic signalling include cotransmission and
      neuromodulation, exocrine and endocrine secretion, platelet aggregation, vascular
      endothelial cell-mediated vasodilatation and nociceptive mechanosensory
      transduction. Examples of slow (trophic) purinergic signalling include cell
      proliferation, differentiation and apoptosis in embryological development, neural
      regeneration, bone resorption, cell turnover of epithelial cells in skin and
      visceral organs, inflammation, wound healing and cancer. Finally the purinoceptor
      subtypes expressed on astrocytes, oligodendrocytes, Schwann cells, microglia,
      Muller cells and enteric glial cells will be summarized as well as evidence for
      non-lytic release of ATP from glial cells.

PMID- 16805423
TI  - Agonists and antagonists for P2 receptors.
AB  - Recent work has identified nucleotide agonists selective for P2Y1, P2Y2 and P2Y6
      receptors and nucleotide antagonists selective for P2Y1, P2Y12 and P2X1
      receptors. Selective non-nucleotide antagonists have been reported for P2Y1,
      P2Y2, P2Y6, P2Y12, P2Y13, P2X(2/3)/P2X3 and P2X7 receptors. For example, the
      dinucleotide INS 37217 (Up4dC) potently activates the P2Y2 receptor, and the non
      nucleotide antagonist A-317491 is selective for P2X(2/3)/P2X3 receptors.
      Nucleotide analogues in which the ribose moiety is substituted by a variety of
      novel ring systems, including conformationally locked moieties, have been
      synthesized as ligands for P2Y receptors. The focus on conformational factors of
      the ribose-like moiety allows the inclusion of general modifications that lead to
      enhanced potency and selectivity. At P2Y1,2,4,11 receptors, there is a preference
      for the North conformation as indicated with (N)-methanocarba analogues. The P2Y1
      antagonist MRS2500 inhibited ADP-induced human platelet aggregation with an IC50
      of 0.95 nM. MRS2365, an (N)-methanocarba analogue of 2-MeSADP, displayed potency
      (EC50) of 0.4nM at the P2Y1 receptor, with >10000-fold selectivity in comparison
      to P2Y12 and P2Y13 receptors. At P2Y6 receptors there is a dramatic preference
      for the South conformation. Three-dimensional structures of P2Y receptors have
      been deduced from structure activity relationships (SAR), mutagenesis and
      modelling studies. Detailed three-dimensional structures of P2X receptors have
      not yet been proposed.

PMID- 16805424
TI  - Regulated release of nucleotides and UDP sugars from astrocytoma cells.
AB  - ATP is co-stored in neurosecretory vesicles together with aminergic compounds and
      is released from neural cells and synaptic terminals via regulated exocytosis.
      ATP also is released from non-neuronal cells including astrocytes and astrocyte
      like cell lines. However, the mechanism(s) involved in ATP release from
      astrocytes and other non-secretory cells remains unclear. ATP release from
      primary astrocytes, astrocytoma, and glioma cells is accompanied by enhanced
      accumulation of extracellular UTP, and we have recently discovered that in
      addition to adenine and uridine nucleotides, astrocytoma cells release UDP
      glucose. It has been illustrated that agonists that promote Ca2+ mobilization,
      e.g. thrombin, promote robust release of ATP from 1321N1 astrocytoma cells.
      Agonist-promoted release of ATP from 1321N1 astrocytoma cells also results in the
      release of UDP-glucose but, unlike fast hydrolysable ATP, UDP-glucose was
      hydrolysed at a markedly slow rate. Since UDP-sugars and ATP are concentrated up
      to 20 times in the lumen of the secretory pathway to serve as substrates for
      glycosyl transferase and phosphorylation reactions, respectively, we propose that
      both constitutive and regulated release of nucleotides and nucleotide-sugars from
      astrocytes involves a vesicular mechanism. Observation that adenine nucleotides,
      uridine nucleotides, and UDP-sugars are released from both resting and stimulated
      astrocytes provides support for the physiological significance of nucleotide- and
      UDP-sugar-sensing P2Y receptors in the brain. These findings also suggest that
      slow hydrolysable UDP-glucose may accomplish long lasting signalling on P2Y14
      receptors expressed in astrocytes.

PMID- 16805425
TI  - Pathophysiological roles of P2 receptors in glial cells.
AB  - Extracellular nucleotides act through specific receptors on target cells: the
      seven ionotropic P2X and the eight G protein-coupled P2Y receptors. All these
      receptors are expressed by brain astroglia and microglia. In astrocytes, P2
      receptors have been implicated in short-term calcium-dependent cell-cell
      communication. Upon mechanical stimulation or activation by other transmitters,
      astrocytes release ATP and respond to ATP with a propagating wave of
      intracellular calcium increases, allowing a homotypic astrocyte-astrocyte
      communication, as well as an heterotypic signalling which also involves neurons,
      oligodendrocytes and microglia. Astrocytic P2 receptors also mediate reactive
      astrogliosis, a reaction contributing to neuronal death in neurodegenerative
      diseases. Signalling leading to inflammatory astrogliosis involves induction of
      cyclo-oxygenase 2 through stimulation of ERK1,2 and of the transcriptional
      factors AP-1 and NF-kappaB. Microglia also express several P2 receptors linked to
      intracellular calcium increases. P2 receptor subtypes are differentially
      regulated by typical proinflammatory signals for these cells (e.g.
      lipopolysaccharide), suggesting specific roles in brain immune responses.
      Globally, these findings highlight the roles of P2 receptors in glial cell
      pathophysiology suggesting a contribution to neurodegenerative diseases
      characterized by excessive gliosis and neuro-inflammation. They also open up the
      possibility of modulating brain damage by ligands selectively targeting the
      specific P2 receptor subtypes involved in the gliotic response.

PMID- 16805426
TI  - Ectonucleotidases in the nervous system.
AB  - Extracellular nucleotides are hydrolysed by enzymes of the plasma membrane with
      an extracellularly oriented catalytic site (ectonucleotidases). Members of
      several families of ectonucleotidases can contribute to extracellular nucleotide
      hydrolysis. They have been characterized in molecular and functional terms. A
      major role of these enzymes is in the modulation of ligand availability at
      nucleotide and nucleoside receptors. The enzymes reveal a wide and partially
      overlapping tissue distribution. The diversity of the individual family members
      is considerable and it is still difficult to assign identified enzymes to the
      modulation of purinergic signalling pathways. In the brain, members of all
      ectonucleotidase-families are expressed. Proposed physiological functions include
      modulation of synaptic transmission, of the ATP-mediated propagation of glial
      Ca2+ waves, of microglial function, adult neurogenesis or the control of vascular
      tone, haemostasis and thromboregulation.

PMID- 16805427
TI  - P2 receptor signalling, proliferation of astrocytes, and expression of molecules
      involved in cell-cell interactions.
AB  - Growing evidence indicates that trophic actions of extracellular nucleotides are
      involved in CNS development, injury and repair. For example, upon CNS injury, ATP
      is released and contributes to the formation of reactive astrocytes, cells that
      produce molecules that can impede or promote axonal regeneration. Proliferation
      is one of the features of reactive astrogliosis, particularly in traumatic
      injury. Fibroblast growth factor (FGF)2 is also increased after injury and can
      stimulate astrocyte proliferation. Extracellular ATP enhances FGF2-induced
      proliferation in a process mediated by P2Y receptors and increased cyclin
      expression. However, when P2X receptors are activated, FGF2-induced proliferation
      is inhibited. P2 receptors are coupled to extracellular signal regulated protein
      kinase (ERK), and differences in the extent and duration of ERK activation by P2Y
      and P2X receptors may mediate the opposing effects of these receptors on FGF2
      induced mitogenesis. Trauma also activates P2 receptor/ERK signalling, and
      stimulation of this and other protein kinase pathways by extracellular ATP
      increases expression of cell adhesion and extracellular matrix molecules involved
      in migration, glial contact formation, neuronal guidance and synapse formation.
      These findings support the hypothesis that purinergic signalling via protein
      kinase cascades plays a key role in astrocyte proliferation, glia-glia
      connections, and neuron-glia interactions in both normal and pathological
      conditions.

PMID- 16805428
TI  - Nerve impulses regulate myelination through purinergic signalling.
AB  - The myelin membrane wrapped around axons provides electrical insulation essential
      for rapid impulse conduction. Impulse activity can affect the formation of
      myelin, but the effects differ in the PNS and CNS, where myelin is formed by two
      distinct types of cells: Schwann cells (SCs) and oligodendrocytes, respectively.
      Our studies on mouse dorsal root ganglion (DRG) neurons, which have axons in both
      the PNS and CNS, show that impulse activity releases ATP from premyelinated
      axons, and that this is detected by myelinating glia. Calcium imaging indicates
      that axonal firing stimulates different purinergic receptors on the two types of
      glia, resulting in opposite effects of impulse activity on differentiation of SCs
      and oligodendrocyte progenitor cells (OPCs). In addition to P2 receptors on both
      types of glia, four types of P1 receptors are present in OPCs, but only A2A and
      A2BP1 receptors are detected in mouse SCs. ATP is of primary importance in
      regulating early development and myelination by SCs, where it inhibits
      differentiation and myelination. Adenosine is of primary importance in regulating
      early development of OPCs, where it stimulates differentiation and myelination.
      Purinergic signalling interacts with growth factor and cytokine signalling, and
      these responses are developmentally regulated.

PMID- 16805429
TI  - Cross-talk between growth factor and purinergic signalling regulates Schwann cell
      proliferation.
AB  - Axons provide multiple mitogenic signals to Schwann cells (SCs), yet at an
      appropriate stage of development, SCs stop dividing despite the mitogenic action
      of axolemma and growth factors. This implies that the effect of mitogens on cell
      proliferation may be context-dependent, having different effects on cell
      proliferation depending upon other signals in the extracellular environment.
      Recent research has shown that the effects of adenosine on SC proliferation
      depend upon the growth factor environment, and that the extracellular signal
      regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signalling pathway
      is an important point of integration between purinergic and growth factor
      signalling. In the absence of growth factors, adenosine is mitogenic and
      associated with stimulation of the ERK/MAPK pathway in SCs. However, in the
      presence of growth factors (platelet-derived growth factor or neuregulin),
      adenosine has the opposite effect, inhibiting proliferation and ERK/MAPK
      activation. Together these findings suggest a mechanism by which increased neural
      impulse activity could modulate growth factor signalling to both positively and
      negatively regulate SC proliferation before the onset of myelination.

PMID- 16805430
TI  - Promoting neurotrophic effects by GPCR ligands.
AB  - The neurotrophins-nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF), NT-3 and NT-4-represent a family of proteins essential for neuronal
      survival and plasticity. Each neurotrophin can signal through two different
      transmembrane receptors, Trk receptor tyrosine kinases and the p75 neurotrophin
      receptor, the first member of the TNF receptor superfamily. Neurotrophic factors
      play an important role in neurodegenerative diseases, as well as neuropsychiatric
      disorders such as depression, bipolar disease and eating disorders. Indeed, a
      number of approaches have been taken to use neurotrophins to treat Alzheimer's
      dementia, amyotrophic lateral sclerosis and peripheral sensory neuropathy.
      However, many of these clinical trails have failed, due to problems in delivery
      and unforeseen side effects of neurotrophic factors. An alternative approach is
      to use ligands in the G protein-coupled receptor (GPCR) family to transactivate
      trophic activities. We have discovered that treatment with adenosine, a
      neuromodulator that acts through G protein-coupled receptors, is capable of
      activating Trk tyrosine kinase receptors. Transactivation of neurotrophic
      receptors by GPCR ligands raise the possibility that small molecules may be used
      to elicit neurotrophic effects for the treatment of neurodegenerative diseases.
      This approach would allow for selective targeting of neurons that express
      specific G protein-coupled receptors and trophic factor receptors. GPCRs
      transduce information provided by extracellular signals to modulate synaptic
      activity and neurotransmission. In addition to the classical G protein
      signalling, GPCR ligands also activate receptor tyrosine kinases (RTK), including
      neurotrophin receptors. Activation of Trk neurotrophin receptors can occur by
      GPCR ligands in the absence of neurotrophins. Adenosine and PACAP (pituitary
      adenylate cyclase activating polypeptide) induce Trk activation specifically
      through their respective GPCRs to promote cell survival. Transactivation of Trks
      by GPCRs has emerged as a new theme in the biology of neurotrophin function.
      Although the precise role of transactivation is unknown, one possibility is that
      it adds a safety factor that might protect neurons from death in the absence of
      neurotrophins. Abnormal activity of the neurotrophin system has been implicated
      in several psychiatric and neurobiological illnesses. However, the lack of
      knowledge about the precise site of neurotrophin dysfunction has compromised the
      ability to improve the efficacy and the safety of drugs used in treatment
      modalities. If small-molecule GPCR ligands can ameliorate neuronal cell loss
      through Trk, transactivation may offer a new strategy for promoting trophic
      effects during neurodegeneration.

PMID- 16805431
TI  - A purinergic dialogue between glia and neurons in the retina.
AB  - Our laboratory has characterized bidirectional signalling between neurons and
      glial cells in the mammalian retina. We find that light-evoked neuronal activity
      elicits Ca2+ increases in Muller cells, specialized glial cells of the retina. A
      flickering light stimulus evokes an increase in the occurrence of Ca2+ transients
      in Muller cells. Addition of adenosine greatly potentiates this light-evoked Ca2+
      response. The purinergic antagonist suramin and the ATP hydrolysing enzyme
      apyrase block the glial Ca2+ response, indicating that neuron to glia signalling
      in the retina is mediated by ATP release from neurons and activation of glial
      purinergic receptors. Glia to neuron signalling has also been observed. Muller
      cell stimulation can evoke a hyperpolarization in neighbouring ganglion cells
      lasting tens of seconds. The hyperpolarization is blocked by the A1 adenosine
      receptor antagonist DPCPX and is reduced by ecto-ATPase and ectonucleotidase
      inhibitors, indicating that the hyperpolarization is mediated by glial release of
      ATP which is converted to adenosine by ecto-enzymes, leading to the activation of
      neuronal adenosine receptors. The existence of bidirectional purinergic
      signalling between neurons and glia suggests that glial cells participate in
      information processing in the retina.

PMID- 16805432
TI  - Bidirectional astrocyte-neuron communication: the many roles of glutamate and
      ATP.
AB  - Glutamatergic and purinergic signalling play key roles in synaptic transmission
      and modulation in the CNS. Here, we review recent evidence showing that glial
      cells, and in particular astrocytes, are active players in ATP and glutamate
      signalling in the brain. ATP and glutamate coordinately activate astrocytes,
      through the mobilization of their internal Ca2+, which in turn triggers the
      release from astrocytes of several neuroactive molecules including ATP and
      glutamate themselves. These 'gliotransmitters' signal either to astrocytes, where
      they generate Ca2+ waves, or to neurons, where they modulate synaptic
      transmission and neuronal excitability. By using microfabricated lanes of
      adhesive substrate, we provide further evidence for a diffusible factor-mediated
      propagation of Ca2+ waves and, through flash photolysis experiments in
      hippocampal slices, we show that glutamate and ATP cooperate in the generation of
      the astrocytic Ca2+ signal. Once astrocytes are activated they provide both
      excitatory and inhibitory effects on neighbouring neurons. Through the Ca2+
      dependent release of glutamate, which acts on extrasynaptic neuronal NMDA
      receptors, astrocytes excite neurons while, in contrast, ATP released from
      astrocytes, after the delayed conversion to adenosine, causes neuronal
      suppression.

PMID- 16805433
TI  - Neuron-glia interactions at the neuromuscular synapse.
AB  - The contribution of glial cells in the regulation of the transfer of information
      in CNS and PNS is now increasingly recognized. Perisynaptic Schwann cells (PSCs),
      glial cells at the neuromuscular junction (NMJ), have proven to be an
      exceptionally important model for studying these roles. PSCs surround nerve
      terminals at the NMJ and are activated by transmitter release in a frequency
      dependent manner. All of these receptors, except one type, are coupled to G
      proteins and can be regrouped into two categories: activators and modulators of
      PSCs. In the former category are muscarinic (unknown subtype) and purinergic
      receptors (P2X and P2Y). In the latter category are adenosine (A1), Substance P
      (NK-1) and CGRP receptors. All receptors coupled to G proteins induce the release
      of Ca2+ from internal stores. In return for this activation, PSCs modulate
      synaptic activity and short-term plasticity. In this review, we will focus on the
      role of purines in the induction of glial cell activity and their possible
      involvement in the modulation of synaptic transmission as a result of the
      synaptic-induced glial activity.

PMID- 16805434
TI  - Functional neuronal-glial anatomical remodelling in the hypothalamus.
AB  - The supraoptic nucleus (SON) of the hypothalamus undergoes a striking anatomical
      remodelling under conditions of intense stimulations like chronic dehydration,
      parturition and lactation. This morphological plasticity modifies the astrocytic
      coverage of magnocellular neurons and their synaptic afferent inputs. These
      changes occur within a few hours and are completely reversible upon the cessation
      of the stimulation. By comparing synaptic transmission and diffusion properties
      before and during this neuroglial remodelling, we have been able to show that the
      astrocytic environment of neurons contributes to the regulation of synaptic and
      extrasynaptic transmission. It appears that the presence of fine astrocytic
      processes enveloping synapses and neuronal elements ensures two important
      functions. First, they control the level of activation of presynaptic
      metabotropic glutamate autoreceptors located on glutamatergic terminals, thereby
      regulating synaptic strength at excitatory synapses. Second, they constitute a
      physical barrier to diffusion, limiting spatially and temporally spill-over of
      neurotransmitters and, as a consequence, extrasynaptic transmission, a process
      essential for intercellular communication. Using the neuroglial anatomical
      remodelling of the SON as an experimental model has brought new insights into the
      role of glial cells in the regulation of synaptic transmission and signal
      processing in the brain.

PMID- 16805435
TI  - Purinergic signalling between axons and microglia.
AB  - Neurons are delicate elements unable to withstand prolonged exposure to the many
      toxic factors that gain access to the CNS or which are made by activated
      leukocytes. The well-being of neurons and their functional properties are
      dependent on glial cells. Microglia have a unique role in this context because
      they are involved in both neuronal support and immunological defence. We now know
      that neuron-microglia communication is bidirectional: neurons and microglia
      continuously exchange messages and integrate information received from
      neighbouring cells. It is now generally accepted that purinergic signalling is a
      key pathway in this continuous flow of information in health and disease. Release
      of ATP from neurons directly modulates microglial cell function eliciting
      secretion of neurotrophic or, in some cases, neurotoxic factors that deeply
      affect neuronal physiology. Purinergic stimulation of microglia P2 receptors
      might in turn elicit a burst of ATP release that feeds back onto the neurons.
      Development of sophisticated techniques for the measurement of extracellular ATP
      now makes possible real-time measurement of ATP release into the pericellular
      space and allows validation of the purinergic hypothesis for neuron-microglia
      signalling.

PMID- 16805436
TI  - ATP receptors of microglia involved in pain.
AB  - Microglia, activated when physiological homeostasis is threatened, play an
      important role as immune cells in the CNS. Activated microglia show a progressive
      series of changes in morphology, gene expression, function and number, and
      produce and release various chemical mediators, including proinflammatory
      cytokines that can produce immunological actions and modify neuronal function.
      Recently, accumulating evidence has indicated an important role for ATP receptors
      of activated microglia in neuropathic pain. Neuropathic pain is often a
      consequence of nerve injury through surgery, bone compression, cancer, diabetes
      or infection. The expression of the P2X4 receptor, a subtype of ATP receptors, is
      enhanced in spinal microglia in a peripheral nerve injury model, and blocking
      pharmacologically and suppressing molecularly P2X4 receptors produces a reduction
      of the neuropathic pain. Several cytokines such as interleukin 6 (IL6) and tumour
      necrosis factor alpha (TNFalpha) in the dorsal horn are also increased after
      nerve lesion and have been implicated in contributing to nerve-injury pain. ATP
      can activate mitogen-activated protein kinase (MAPK) leading to the release of
      bioactive substances including cytokines from microglia. Thus, diffusible factors
      released from activated microglia by the stimulation of purinergic receptors may
      have an important role in the development of neuropathic pain.

PMID- 16805437
TI  - Defense of benthic invertebrates against surface colonization by larvae: a
      chemical arms race.
AB  - Sessile invertebrates evolved in a competitive milieu where space is a limiting
      resource, setting off an arms race between adults that must maintain clean
      surfaces and larvae that must locate and attach to a suitable substratum. I
      review the evidence that invertebrates chemically deter or kill the propagules of
      fouling animals and protists under natural conditions, and that chemosensory
      mechanisms may allow larvae to detect and avoid settling on chemically protected
      organisms. The fouling process is an ecologically complex web of interactions
      between basibionts, surface-colonizing microbes, and fouling larvae, all mediated
      by chemical signaling. Host-specific bacterial communities are maintained by many
      invertebrates, and may inhibit fouling by chemical deterrence of larvae, or by
      preventing biofilm formation by inductive strains. Larval settlement naturally
      occurs in a turbulent environment, yet the effects of waterborne versus surface
      adsorbed chemical defenses have not been compared in flow, limiting our
      understanding of how larvae respond to toxic surfaces in the field. The
      importance of evaluating alternative hypotheses such as mechanical and physical
      defense is discussed, as is the need for ecologically relevant bioassays that
      quantify effects on larval behavior and identify compounds likely to play a
      defensive role in situ.

PMID- 16805438
TI  - Furanones.
AB  - The red alga Delisea pulchra has been a model organism for understanding the
      ecological role of secondary metabolites as natural antifoulants. Furanones are
      produced by the plant and delivered to the surface at a concentration where they
      regulate bacterial colonisation and the settlement of epibiota. This biological
      understanding has led to the application of furanones as inhibitors of bacterial-
      and macro-fouling. Furanones inhibit bacterial colonisation and biofilm
      development through interference with a key bacterial quorum-sensing pathway, the
      acylated homoserine lactone regulatory system in Gram-negative bacteria. They
      also interfere with the alternative AI-2 signalling system in Gram-negative and
      Gram-positive bacteria. Synthetic programs have developed a library of more than
      200 furanone and furanone-analogues including surface attached-furanones. These
      furanone analogues are potent anti-infectives and inhibit pathogenic phenotypes
      in Gram-negative and Gram-positive bacteria as demonstrated in-vitro using gene
      microarrays, and in-vivo using mouse models. Additionally, furanones inhibit the
      expression of bacterial exo-enzymes that actively degrade components of the
      immune system thereby enhancing the immune response. Surface-attached furanones
      immobilised on catheters also inhibit bacterial attachment and retain activity
      for extended periods. Furanones are strong deterrents of the settlement and
      growth of macrofouling organisms and as such have potential application as a
      marine antifouling technology. Laboratory antifouling assays have been used to
      identify effective and safe furanone-analogues while field trials of furanones
      incorporated into coatings and polymers demonstrate efficacies similar to
      commercial biocides. Further development is required to control the release of
      compounds from suitable carriers to extend coating/polymer lifespans. This review
      summarises the extensive work on furanones focusing on their natural and applied
      antifouling activities.

PMID- 16805439
TI  - Isocyano compounds as non-toxic antifoulants.
AB  - The marine sponge Acanthella cavernosa and nudibranchs of the family Phyllidiidae
      contain isocyanoterpenoids and their related compounds that show potent
      antifouling activity against cypris larvae of the barnacle Balanus amphitrite,
      while their toxicity to cyprids is weak. To develop non-toxic antifoulants based
      on isocyanoterpenoids, especially 3-isocyanotheonellin, a total of 36 isocyano
      compounds have been synthesized. They were evaluated by both antifouling activity
      and toxicity toward B. amphitrite cyprids, which led some insight into the
      structure-activity relationships. Since linear alkyl isocyanides showed
      antifouling activity at nontoxic concentrations, a large amount of 1,1-dimethyl
      10-undecyl isocyanide was synthesized, incorporated into paints, and tested for
      antifouling activity in the field with promising results. Therefore, isocyano
      compounds were considered as candidate non-toxic antifouling agents.

PMID- 16805440
TI  - 3-Alkylpyridinium compounds as potential non-toxic antifouling agents.
AB  - To date, around thirty bioactive 3-alkylpyridinium compounds, either in monomeric
      or oligomeric forms, have been identified in marine sponges belonging to the
      order Haplosclerida In this work, we have reviewed their biological activities,
      which include mainly cytotoxicity, ichthyotoxicity, inhibition of bacterial
      growth, and enzyme inhibition. Most of these activities increase with the
      increasing degree of oligomerization of the corresponding 3-alkylpyridinium
      compound. It was shown recently that 3-alkylpyridines also exhibit promising
      antifouling activities. Linear 3-octylpyridinium polymers (Poly-APS), isolated
      from the Mediterranean sponge Reniera sarai, showed a non-toxic reversible
      mechanism of settlement inhibition of Balanus amphitrite cypris larvae with an
      EC50 of 0.27 microg/mL. At the same time, their toxicity towards the organisms
      used in the toxicity bioassays (B. amphitrite nauplii, microalga Tetraselmis
      suecica and larvae of Mytilus galloprovincialis) was almost negligible in
      comparison to commercially available and currently used booster biocides based on
      copper and zinc complexes with pyrithione. Poly-APS and some other natural 3
      alkylpyridines were also found to be very effective in preventing microbial
      biofilm formation. Preliminary tests have confirmed that some monomeric and
      oligomeric synthetic analogues of poly-APS also exert antifouling activity, which
      makes these compounds promising candidates as new environmentally-friendly
      ingredients in the new generation of antifouling coatings.

PMID- 16805441
TI  - 5,6-Dichloro-1-methylgramine, a non-toxic antifoulant derived from a marine
      natural product.
AB  - The laboratory culture of the barnacle, Balanus amphitrite has made it possible
      to supply cypris larvae for antifouling assays all year round. The settlement of
      cyprids obtained from cultured B. amphitrite was indistinguishable from cyprids
      reared from field-collected barnacles. In laboratory cyprid settlement assays of
      extracts from marine sessile organisms, antifouling activity was expressed as the
      99% inhibitory concentration (IC99), and toxicity as the 30% lethal concentration
      (LC30). The lipophilic extract of the marine bryozoan, Zoobotryon pellucidum,
      which showed promising antifouling activity, yielded 2,5,6-tribromo-1
      methylgramine (TBG) by bioassay-guided isolation. The inhibitory activity of TBG
      was 6 times as strong as that of bis-(n-butyltin)oxide (TBTO), while its toxicity
      to cypris larvae was one-tenth that of TBTO. A structure-activity relationship
      study with 155 indole derivatives led to the discovery of the non-toxic
      antifoulant candidates 5,6-dichlorogramine, 5-chloro-2-methylgramine, and 5,6
      dichrolo-1-methylgramine (DCMG), the latter being selected as the antifouling
      paint ingredient for performance evaluation tests (panel tests) following the
      results of a preliminary safety tests. A silicone-based antifouling paint
      containing 5-10% of DCMG was prepared and tested in the field; the painted
      surfaces remained almost barnacle-free for 1.5 years similar to silicone coatings
      such as Biox. Since the leaching rate of DCMG from the paint surface could be
      controlled by the addition of an acrylic acid-styrene copolymer (ASP), the life
      of the antifouling performance is expected to be improved. Thus, an extremely non
      toxic silicone-based antifouling paint containing DCMG is under development.

PMID- 16805442
TI  - Biofilms.
AB  - Biofilms of bacteria, frequently in association with algae, protozoa and fungi,
      are found on all submerged structures in the marine environment. Although it is
      likely that for the majority of organisms a biofilmed surface is not a pre
      requisite for settlement, in practice, colonization by spores and larvae of
      fouling organisms almost always takes place via a biofilmed surface. Therefore,
      the properties of the latter may be expected to influence colonization,
      positively or negatively. Biofilms are responsible for a range of surface
      associated and diffusible signals, which may moderate the settling behaviour of
      cells, spores and larvae. However, there is no consensus view regarding either
      cause and effect or the mechanism(s) by which biofilms moderate settlement.
      Studies with mixed biofilms, especially field experiments, are difficult to
      interpret because of the conflicting signals produced by different members of the
      biofilm community as well as their spatial organisation. Molecular techniques
      highlight the deficiencies of culture methods in identifying biofilm bacteria;
      hence, the strains with the most impact on settlement of spores and larvae may
      not yet have been isolated and cultured. Furthermore, secondary products isolated
      from cultured organisms may not reflect the situation that pertains in nature.
      The evidence that bacterial quorum sensing signal molecules stimulate settlement
      of spores of the green macroalga, Ulva, is discussed in some detail. New
      molecular and analytical tools should provide the opportunity to improve our
      fundamental understanding of the interactions between fouling organisms and
      biofilms, which in turn may inform novel strategies to control biofouling.

PMID- 16805443
TI  - Adrenoceptor and other pharmacoactive compounds as putative antifoulants.
AB  - The search for new antifouling methods, which are non-hazardous for the marine
      environment, is intense. However, even if several innovations in this field of
      research have been made, the search for unique molecules with characteristics
      such as strong biological activity, low residence time in the marine environment
      and which target special physiological features in marine invertebrate larvae,
      biofilm forming bacteria or algal spores is still required. This chapter reviews
      the effects of biogenic amine receptor agonists and antagonists, primarily G
      protein-coupled receptors, on settling barnacle cypris larvae. Biotechnological
      research on adrenoceptor compounds as lead molecules in new antifouling
      technologies is also reviewed.

PMID- 16805444
TI  - State-of-art methodology of marine natural products chemistry: structure
      determination with extremely small sample amounts.
AB  - Structure elucidation studies on natural products are reviewed emphasizing
      extremely small sample amounts. Previous studies on insect pheromones,
      periplanones, and bean-originating kairomones, glycinoeclepins, are described
      briefly. Recent examples are selected from marine natural products such as
      ciguatoxin, dolastatin-3, and aurisides. A more detailed description is given of
      a sperm-activating and attracting factor (SAAF), which may be the smallest sample
      amount used in the structure elucidation of novel non-peptidic natural products.
      SAAF was isolated from the eggs of the ascidian, Ciona intestinalis, and its
      structure was deduced with only approximately 4 microg (6 nmol) of sample. Based
      upon the proposed structure, two epimers were synthesized from chenodeoxycholic
      acid in 17 steps, leading to the identification of SAAF as a novel sterol
      sulfate.

PMID- 16805445
TI  - [Scientific evidence in occupational medicine: meta-analysis of the data
      regarding the effects of working with video terminals on the psycho-physical well
      being].
AB  - Psycho-physical well-being of video display terminal (VDT) workers is often
      neglected. The aim of this study is to evaluate, through the comparison of
      controlled studies published in scientific literature, the psycho-physical well
      being of VDT workers and, in particular way, the phenomena of strain and mental
      fatigue with their neuro-physiological, behavioural and subjective components.
      Seven-hundreds articles have been found from which we have selected twenty-one
      articles on the basis of the following inclusion criteria: controlled studies and
      evaluation of variables about mental fatigue; finally, only fifteen articles were
      utilized in the analysis due to the variability of data needed in the computation
      of effect size. For continuous variables we have performed two different types of
      elaboration methods; in case of variables showing no significant heterogeneity
      among studies, we have used the Weighted Mean Difference method, according to the
      Fixed Effect Model, while for variables showing significant heterogeneity among
      studies, we have used the Standardized Mean Difference method according to the
      Random Effects Model. Categorical variables have been analyzed trough the
      calculation of Odds Ratio according to the Fixed Effect Model or to the Random
      Effects Model respectively in case of heterogeneity's absence or presence among
      studies. Variables obtained by the studies were classified in four groups:
      biological assessment, strain assessment, subjective well-being assessment, and
      psycho-somatic symptoms. Statistically significant outcomes have been found for
      urinary adrenalin, sleep disturbances and for all the evaluated categorical
      parameters except headache. These outcomes allow for the following observations:
      1) psycho-physical well-being of VDT workers, and especially mental fatigue,
      remain an object of uncertain identification and they are often neglected by
      Occupational Health doctors even though their evaluation is required by the
      Italian legislation (D.Lgs 626/94); 2) even though there is a huge interest on
      the argument, the amount of controlled studies on VDT workers is still
      insufficient. Furthermore, studies are often weak in power heterogeneous and
      discordant on potential problematic issues and consequently there is a difficulty
      in both the reproduction and overlapping of the studies; 3) Occupational Health
      doctor should be more careful toward this specific argument and, in his clinical
      practice, he should use only evidence-based parameters with high level of
      reproduction suggested by studied which can be considered homogeneous and
      overlapping for case studies and control groups. This meta-analysis suggests
      which evaluations to use as statistically significant parameters for the health
      protection of VDT workers.

PMID- 16805446
TI  - [Exposure to arsenic in the manufacture of glass rods. Results of the biological
      monitoring and preventive indications].
AB  - Nowadays arsenic trioxid is still used in the hand made glass production in
      Murano. In the last years, many industries have reduced its use but, in some
      specific lines of production, such as the "bacchetta di vetro" for the secondary
      "a lume" production, there is still a considerable use. Biological monitoring,
      carried out through urinary arsenic measurement, shows as workers employed in the
      mixture preparation and in the furnace work, are still significantly exposed to
      arsenic, despite the technical preventive measures adopted. We propose further
      measures to reduce this risk.

PMID- 16805447
TI  - [Significance of the synergy between the ASL and the Association of Formerly
      Exposed to Asbestos].
AB  - In Frosinone's district there is a lot of attention for ex-exposed to asbestos
      problems. The aim of this study is to demonstrate the importance of synergy
      between AEA (ex-exposed to asbestos workers association) and the Health Service
      Unit (ASL) of Frosinone for timely diagnosis of professional diseases.

PMID- 16805448
TI  - [Health surveillance of subjects formerly exposed to asbestos in Puglia].
AB  - The massive use of asbestos affected several industrial areas of Apulian region
      in the last decade. It has been estimated that in our country there are thousands
      of asbestos exposed workers and about 10.000 of them received CONTARP-INAIL
      document attesting their asbestos exposure for over ten years ex D.L. 257/92.
      Owing to the lack of any regional rules and guidelines on the medical
      surveillance of asbestos ex-exposed people, since 1994 our operative hospital
      unit has activated a sanitary protocol in order to satisfy growing requests of
      assistance and emergent controls for this part of people. During a 12 year
      activity 629 asbestos ex-exposed workers have been examined. 21% of these workers
      had two checks, thanks to these the recognition of 22 new tumoral and non-tumoral
      asbestos-correlated pathologies has been possible. This experience makes it clear
      that the activation of new procedures for early diagnoses of some asbestos
      correlated pathologies is necessary, in fact more proposals for a redevelopment
      of sanitary assistance in the regional field are suggested.

PMID- 16805449
TI  - [Poliomyelitis vaccine contaminated with SV40 and prior exposure to asbestos:
      cognitive study in a group of car repair workers].
AB  - Pleural and pulmonary malignancies are usually associated with previous asbestos
      exposure and the presence of simian virus 40 (SV40) has been detected in these
      neoplasms. Our study aimed to investigate the health situation among mechanics
      servicing buses, ex-exposed to asbestos, who received polio vaccines contaminated
      by SV 40. We conducted a descriptive study and so we recruited, on the basis of
      birth date and duration in the current job, 39 mechanics, born since 1950 until
      1965, with length of service above 15 years. Of all subjects a clinical
      examination, a lung function test and a chest radiograph were obtained. More than
      30% of sample showed pharynx and larynx clinical alterations and radiological
      signs of previous exposure to asbestos. We didn't find pleural or pulmonary
      malignancies; besides 4 doubtful neoplasms required further investigations.
      Although exiguity of sample, these findings provide a lack of mesothelioma and
      lung cancer among mechanics, previously exposed to asbestos and infected by SV40.

PMID- 16805450
TI  - [Health surveillance of workers with prior exposure to asbestos. Application in
      the metallurgy/metal mechanical field].
AB  - To improve the health surveillance program for workers with a known previous
      exposure to asbestos in a big metallurgic-mechanical industry from Lombardy, the
      sources of risk and the different exposure levels hare been reconstructed based
      on specific jobs. The eligibility criteria and a specific work program including
      information and organization supports hare been established by a work group
      composed by health physicians, workers and industrial hygienists. The major goals
      of the program were: to listen and support each worker who perceives worries
      about his health status; to prevent, if possible, diseases, especially cancer,
      resulting from exposure; to document the existing injuries for legal
      compensation. The resulting actions consist of counselling; indication to follow
      an adequate life and work style; indication, based on specific request of worker,
      of sanitary checks of first or eventually second level.

PMID- 16805451
TI  - [Occupational fitness of workers with fibromyalgia syndrome].
AB  - Fibromyalgia is a syndrome characterized by widespread musculoskeletal chronic
      pain and by other clinical manifestations such as stiffness, fatigue, sleep
      disturbances, anxiety and depression. The disorder has a considerable impact on
      the ability to perform work and daily living activities, often reducing workforce
      participation. Fitness to work, in relation to biomechanically taxing tasks
      execution, vibration exposure, environmental microclimatic conditions and night
      shift, is discussed.

PMID- 16805452
TI  - [Identification and control of workers that pose a risk to others in the health
      field].
AB  - BACKGROUND: Working in health care increases the probability that an impaired
      worker be hazardous for third persons. METHODS: A literature review concerning
      identification, intervention, and treatment of hazardous health care workers is
      here reported. RESULTS: Published reports of health care worker-to-patient
      transmission of bloodborne infections, and papers concerning the so-called
      "impaired physician", have been reviewed. DISCUSSION: According to European
      directives on workers' health and safety, the occupational health physician
      charged of 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 are given.

PMID- 16805453
TI  - [Usefulness of spiral CT in the prevention of pulmonary barotrauma: presentation
      of a case report in a hyperbaric operator].
AB  - A medical surveillance integrated system for health care workers, engaged in an
      hyperbaric environment exposure, was set upped and implemented in an university
      hospital, in accordance with doctrinal, legislative and methodological issues. In
      particular, a specific attention on anatomic and functional assessment of the
      respiratory system was applied, through an advanced technique of spiral-CT
      imaging, with the aim to carry out an early detection of conditions to be
      predispose "pulmonary barotrauma". Therefore, the present contribution proposes
      to illustrate clinical and instrumental data, and also to show chest spiral-CT
      acquired images results, in a 35-years-old nurse on assignment to an hyperbaric
      oxygen therapy unit. In this experience the described preventive protocol was
      operated in the context of a modern rational and justifiable, flexible and
      balanced health protection path.

PMID- 16805454
TI  - [Assessment of the efficacy of limitations and indications issued by the
      occupational physician regarding the health of the staff working in public
      transportation vehicles].
AB  - In this study we assessed the evidence of some specific, "ad hoc", medical
      indications for city bus, tram and subway professional drivers. As known,
      professional drivers have very little chances of modifying shift organization and
      many chronic degenerative diseases (low back pain, diabetes type 2,
      cardiovascular diseases, ecc.) are difficult to manage according to job planning.
      In our study we observed a positive association between introduction of specific
      shift, in particular when shift is divided in two-piece, on morning "turno
      spezzato 1(0)/1(0)" or one on morning and the second part on afternoon "turno
      binato 1(0)/2(0)". Evidence of the real impact on professional drivers health
      conditions has been found from analysis of sickness leave during two, or in same
      case, one year before and after such medical indications intoduction. In our
      occupational drivers cohort a positive association, evidence based on real rates
      of two years sick absence before and after medical indications, was found between
      improvement of health general conditions and reduction of sickness leave rates
      correlated.

PMID- 16805455
TI  - [Symptoms and musculo-skeletal changes among personnel of the State Police
      exposed to mechanical risk].
AB  - The aim of this present study was to inquire about spine morfo-functional
      alterations among policemen with jobs regarded as potentially hazardous, in order
      to identify preclinical alterations of column and to plan adequate preventive
      measures. A physiopathologic and working anamnesis was carried out by means of
      questionnaire about personal data, jobs, reported rachidian symptomatology and
      presence of orthopedic diseases, given to policemen on duty in Bari. Every chosen
      worker was subject to orthopedic and neurological examination, radiography of
      column, Formetric tridimensional examination, telethermography of spine. We
      stratified the sample on the basis of age and job. Under the jobs we individuated
      4 biomechanical hazardous activities, performed separately or together: driving
      motorcycle, driving car, flying helicopter, video terminal use. The whole sample,
      formed by 211 subjects, all male, had the average age of 39 years (Standard
      Deviation: +/- 4). About the reported rachidian symptomatology, only 41 (17, 98%)
      subjects were asymptomatical, contrary to clinical results, that were normal in
      almost the entire sample, with the exception of 3 workers (1, 31%), who had
      neurological clinical alterations. Structural alterations were checked by
      radiography among 64, 9% of subjects. The Formetric examination found alterations
      in different tract of rachis, also coexiting between each other. The
      telethermographic changes affected 63,99% of the sample and involved especially
      the lumbar tract (38,86%), dorsal region (18%) and cervical zone (7,1%). The
      relative frequency of dorsal tract increased with growing of age. The morfo
      functional changes of the sample seem to depend rather on the performed job, than
      on degenerative process of age, partly because the average age of the sample is
      not much elevated and because the enlistment in Italian Police Force is
      subordinated to verification of optimum conditions, also characterized by absence
      of anomaly of column. The absence of clinical alteration, in contrast to reported
      rachidian symptomatology by 82,02% of subjects and with discovered objectivity,
      demands more clinical attention in presence of symptomatology and proposes
      supplementary non-invasive techiniques of investigation, as the telethermography
      and the formetric tridimensional examination.

PMID- 16805456
TI  - [Musculo-skeletal disorders and diseases in the complex metal-mechanical
      industry].
AB  - Among work-related diseases, musculoskeletal disorders of the upper extremities
      have obtained increasing attention in last decades. In this paper we present and
      discuss the results of a work place ergonomic survey in a complex manufactory
      industry (Indesit S.p.A.), considering upper limbs disorders for biomechanical
      work-load risk. Ergonomic analysis has been performed using OCRA check-list,
      ORAGE method and Strain Index (S.I.). Results highlight the effectiveness use of
      the three arranged methods to assess risk situations and improve work places
      ergonomics conditions.

PMID- 16805457
TI  - [Biomechanical overload of the arm: experience with risk prevention in the
      Fabrian metal-mechanical industry].
AB  - In the year 2000, the S.P.S.A.L. of Fabriano territorial zone, after a high
      number of reported cases of CTS in the Orthopedic Unit of the local hospital,
      started an informative and preventive study program on the risk of biomechanical
      overloading of the upper extremities. The study was divided in four main steps:
      1. Epidemiological study I. A questionnaire assessing professional and
      pathological anamnesis, musculoskeletal disorders of the upper extremities as
      well as the professional and non professional risk factors was administered to
      448 assembly line workers in seven metal mechanic factories (2000-2001). 2.
      Lecture for the proposed institution to communicate the results of study I
      (2001). 3. Evaluation of the trend on professional diseases reported by medical
      doctors and verified by INAL during the years 1999-2005. 4. Epidemiological study
      II. The same questionnaire from the first study has been administered to 448
      assembly line workers in the same industries selected for the previous
      investigation (2005). The first study results, presented in the December 2001
      lecture from the supervising institution, indicated the departments at risk and
      showed the necessity of collaboration between specific departments and
      specialized medical doctors to achieve a rapid diagnosis of work-related
      diseases. Following our data, the companies have adopted preventative measures,
      scientific methods of specific risk evaluation as well specific protocols of
      health survey. Both the reported and the verified diseases showed an increment
      starting from 2002. The comparison between the two studies demonstrated that the
      second group had a reduction in the CTS prevalence and in the other work-related
      upper extremities disorders; a reduction in the repetitive movements, in the use
      of vibrating instruments and work force; an increment in the number of working
      pauses and rotation exercises; an increment in the position switch following the
      appearance of the disorders. However, the results obtained show a fundamental
      discrepancy: a better trend has been observed in the big companies, but it is
      still not sufficient in the smaller companies.

PMID- 16805458
TI  - [Carpal tunnel syndrome among cashiers in commercial businesses].
AB  - The Check-out assistants represent a working sector at risk of Work Related
      Musculo Skeletal Disorders (WMSDs). The aim of our study is to evaluate carpal
      tunnel syndrome's incidence in check out assistants. Our search was carried out
      on a sample of 695 female check-out assistants,after a specific risk's valutazion
      witch "chec-list application", during health surveillance. Subjects with an
      pand's painful symptoms or paraesthesias along territory of median were submitted
      to tests thath revial compression of median at wrist: Phalen and Tinel tests. Who
      were positive to painful symptoms or paraesthesias in both tests, were subjected
      to electromyographia (E.M.G.), gold standard for carpal tunnel Syndrome
      diagnosis. This sample was compared with a control group no-exposed to specific
      risk (all teachers) of equal number, age, sex and working age of our sample. Our
      results point out that: our study sample show more symptoms and carpal tunnel
      Syndrome than the control group; tere aren't statistically meaningful differences
      between test's positive subjects amd EMG positive subjects. We demonstrated that
      a careful anamnesis and objective exam can replace EMG.

PMID- 16805459
TI  - [Assessment of the risk of occupational biomechanical overload: comparison of
      methods currently used].
AB  - Some of the most common methods for the evaluation of the ergonomic risk of Work
      Related Musculo Skeletal Disorders were applied to different workplaces. The
      results show that an evaluation of the single components of the synthetic risk
      indices given by the methods is needed to evidence the specific critical aspects.

PMID- 16805460
TI  - [Application of a protocol for assessing occupational fitness of workers with UE
      WMSDS in a second-level hospital center: first results].
AB  - It's presented a cluster of 99 workers affected by UEWMSDs examinated in the
      Occupational Medicine Department--University of Turin. The object of the
      evaluation is the critical exam of ergonomic informations, the evalution of the
      fitness to work and the customed return to work.

PMID- 16805461
TI  - [Occupational exposure to glutaraldehyde in the hospital setting].
AB  - Glutaraldehyde (GTA) solutions can be used for low-temperature endoscopes
      disinfection. The research aim was to evaluate the aldehyde air-contamination in
      Campania hospitals operating theatres produced by the use of two-percent
      glutaraldehyde alkaline solution. Air samples were analysed by HPLC-UV (Hight
      Performance Liquid Chromatography with UV detection). The final results show that
      some operating theatres have a significant GTA air-contamination with a substance
      concentration upper limit value (0,05 ppm), due to not-well ventilated workplaces
      and the presence of not-automatic washing units.

PMID- 16805462
TI  - [Exposure to low doses of inorganic lead and arterial pressure among fire arm
      instructors of the Italian State Police].
AB  - Firearm instructors represent a particular occupational group exposed to low lead
      (Pb) doses. Even low blood lead levels (PbB) of this metal can cause an increase
      of blood pressure (BP). OBJECTIVE: To assess the Pb exposure of the firearm
      instructors of the Italian State Police (SP) and the effects of Pb on their PA.
      SUBJECTS AND METHODS: 376 instructors were studied, including 188 subjects
      working at indoor and 188 at outdoorfiring ranges. After obtaining informed
      consent, information on work, social and pathological history was collected and
      measurements of body mass index (BMI), BP and blood lead (PbB) level were
      obtained from the medical records. RESULTS: The mean PbB level of the instructors
      of outdoor ranges (6.7 +/- 5.3 microg/dl) was significantly lower than those of
      indoor ranges (8.5 +/- 7.6 microg/dl). In the instructors of outdoor ranges the
      diastolic BP (DBP) was significantly influenced by BMI and PbB, also considering
      the common confounding factors. DISCUSSION: The mean PbB level of the firearm
      instructors of the Italian SP resulted to be clearly below the biological limit
      value for Pb. In the instructors of outdoor ranges the even low PbB levels
      detected were able to determine a slight, but significant increase of DBP, also
      after correction for the main confounding variables. It is therefore necessary to
      keep on effecting biological monitoring and health surveillance of firearm
      instructors of SP and to promote the reduction of their body weight.

PMID- 16805463
TI  - [Chemical risk of exposure to volatile organic compounds in the field of
      restoration of art objects].
AB  - The use of chemicals during restoration practices involves emissions of toxics
      depending on both the amount of original products used and the specific
      techniques applied. Restorers perform a great variety of techniques by using not
      standardized operative procedures: moreover, they are exposed to mixtures and
      very rarely to single chemicals. In this study we evaluated workers' exposure to
      solvent mixture which were generated during restoration of archaeological metal
      handcraft. Exposure to low levels of twelve organic compounds has been
      experimented inside a public restoration laboratory: based on the data presented
      in this article we assume that inside restoration workplaces a diffused indoor
      contamination can take place. The indoor pollution can generate a risk of an
      uncontrolled exposure to volatile mixtures: therefore the emissions of solvents
      during restoration practices has to be avoided even if they cause a low level of
      exposure.

PMID- 16805464
TI  - [Determination of aromatic polycyclic hydrocarbons during the installation of
      bituminous acoustic insulation panels].
AB  - Two kinds of bituminous European and Asiatic origin panels, used as acoustic
      insulators in the production of electrical household appliances have been
      analysed. The tests, made at 180 degrees C, operation temperature during the
      assembly phases, have been executed by sampling the smokes released during the
      thermal treatment, subsequently analysed by GC-MS. The results showed a marked
      difference between the two samples in the amount of the issued compounds,
      essentially constituted by alkyl-aromatic hydrocarbons, IPA and Alkyl-IPA.

PMID- 16805465
TI  - [Evaluation of the role of occupational and environmental exposure to inorganic
      arsenic in the urinary excretion of the metal: preliminary data].
AB  - INTRODUCTION: Urinary inorganic arsenic is an expression of occupational exposure
      to the metal, provided that there is no history of ingestion of foods containing
      high concentrations of inorganic and/or organic arsenic. The present study was
      conducted to assess the contribution of professional and environmental exposure
      to inorganic arsenic on urinary excretion of the metal. MATERIALS AND METHODS: We
      examined 195 workers at a steelfoundry in Taranto, exposed to very low
      concentrations of inorganic arsenic and two control groups consisting of 105
      subjects resident near the factory and 144 subjects resident approximately 20 Km
      away. All participants were administered a questionnaire enquiring about general
      characteristics, lifestyle, occupational and extra occupational exposure to
      arsenic. Urinary arsenic was determined by atomic-absorption spectrophotometry.
      RESULTS: Exposed and non exposed subjects were similar as regards general
      characteristics and lifestyle. The environmental concentration of arsenic for the
      foundryworkers was invariably lower than 0.1 microg/m3. Urinary excretion of
      arsenic was higher in the subjects in all three groups, examined singly and
      together, if they had eaten crustaceans and/or shellfish in the three days before
      urine collection. There was a significant positive correlation with the
      consumption of shellfish and a significant negative correlation with the number
      of days since the last crustacean/shellfish meal. Multiple regression analysis
      showed a dependence of urinary elimination of arsenic on the days since the last
      crustacean/shellfish meal. DISCUSSION: The absence of occupational exposure to
      arsenic allowed us to attribute the higher urinary elimination of arsenic to
      ingestion of crustaceans and/or shellfish in the three days before collection of
      the urine, both in subjects exposed to inorganic arsenic and in the two groups
      belonging to the general population. Our results support the hypothesis that
      inorganic arsenic, determined by atomic-absorption spectrophotometry, may derive
      from the catabolism of organic arsenic compounds contained in crustaceans and/or
      shellfish included in the diet.

PMID- 16805466
TI  - [Biomonitoring of iridium in a urban population].
AB  - Iridium (Ir) is one of the six elements collectively known as the platinum group
      metals. For its excellent catalytic properties, Ir was recently introduced into
      DeNOx, a new generation of automotive catalysts. The aim of our study was to
      evaluate urinary Ir levels in an urban population. A total of 122 healthy male
      subjects of Rome (Italy) were studied. Ir quantification in the urine samples of
      these subjects was carried out by sector field inductively coupled plasma mass
      spectrometry. The mean urinary Ir level was 10.41 ng/g creatinine (standard
      deviation: 9.67; 25th-75th percentile: 3,62-12,74 ng/g creatinine). The
      scientific community should respond to a potential increase in environmental
      exposure to Ir, due to its growing use as a catalyst, with very careful
      evaluation of the biological levels of this metal and monitoring of airborne
      particulate present in the life environment. Further investigation will enable
      researchers to confirm and integrate the findings of our present study undertaken
      in the context of surveillance.

PMID- 16805467
TI  - [Determination of free and total S-phenylmercapturic acid in the biologic
      monitoring of exposure to benzene].
AB  - One of the biomarkers suggested by the ACGIH to assess the professional exposure
      to benzene is the S-phenylmercapturic acid in the end-shift urine. The existence
      in the urine of N-acetyl-S(1,2-dihydro-2hydroxypHenyl)-L-Cysteine, a precursor of
      SPMA that can be turned into it by acid hydrolysis, is a possible cause of
      miscorrelation between environmental and biological monitoring. The amount of
      measured SPMA depends on the degree of hydrolysis and therefore it is a function
      both of the urine PH and of the storage conditions of the sample. 40 urine
      samples have been collected from workers exposed to benzene, both smokers and not
      smokers, and for each sample the percentage of SPMA measurable at pH 2 and
      without pH correction (free SPMA) has been calculated with respect to the SPMA
      measured after quantitative hydrolysis, with the objectives to determine if a
      correct assessment of the exposure requires the determination of total SPMA and
      which concentration value could correspond to the BEI of 25 microg/g of
      creatinine established by the ACGIH. An aliquot of the urine samples has been
      treated with 9M H2SO4, a second one is brought to pH 2 and a third one is
      analyzed as it is. All samples are analyzed by HPLC/MS/MS in negative ions/MRM
      mode, and quantitative analysis is performed using the internal standard method.
      The percentage found in samples treated at pH 2 is on average 45% of the total
      SPMA for smokers and 60% for non smokers, while the free SPMA varies from 1% to
      66% due to the urine pH variability and to the lower concentrations detected. The
      determination of total SPMA allows the standardization of the
      preanalyticalfactors and the dosage with analytical methods less sensitive than
      HPLC/MS/MS.

PMID- 16805468
TI  - [The use of genetically modified microorganisms in agriculture to reduce or
      eliminate pesticide exposure].
AB  - P. graminea is the casual agent of barley leaf stripe. An early selection method
      of resistant types of barley leaf stripe was realized and validated in this
      research. This new method, based on Microrganism Genetically Modified (MOGM) GUS2
      construction, obtains results comparable with those of classical method, reduces
      the work time, the use of chemicals (pesticides) and productive plants as
      greenhouses. Moreover, the use of MOGM GUS2 is restricted in laboratory ambient,
      therefore the risk of environmental spread is reduced. The early selection method
      has allowed to estimate the reaction to P. graminea agent in 12 several barley
      types usually farmed in Italy. The results were compared both, with the classical
      method data based on artificial clone Dg2 inoculum, and with natural inoculum
      data obtained in field. At all times we observed a ranking likeness.

PMID- 16805469
TI  - [Evaluation of myopia in a group of people working with video terminals: first
      results].
AB  - Since the 70's the occupational use of electronic systems equipped with visual
      display terminals (VDTs) became wide-spread also in Italy. Some longitudinal
      studies on large samples of VDT workers found no significant changes of myopia
      (M) with regard to years and daily hours spent working at a VDT. OBJECTIVE: To
      evaluate the prevalence and the time course of M in 209 VDT workers employed in
      the service sector. MATERIALS AND METHODS: After obtaining workers' informed
      consent their work, social, family and personal medical histories were collected.
      Myopia was defined as need of >0.25 D negative spherical correction. Average
      daily hours duringfollow-up and overall years spent working at a VDT were
      calculated as exposure indexes. RESULTS: The mean baseline age was 39.2 years
      (SD: 8.7, min-max: 22-62) and the mean education was 14 years (SD: 2.2). The mean
      follow-up period was 5.5 (3-9) years. The prevalence of M was 45.5% at the start
      and 49.8% at the end of the study. It was higher in workers with >13 years of
      education and in those < 40 year-old. A slight but significant increase of the
      degree of M (dioptres) occurred during the follow-up. The change in the degree of
      M was not different between the classes of VDT exposure (< or = 4 and >4 daily
      hours; < or =15 and >15 years spent), of education and of age at the end of
      follow-up. DISCUSSION: The high mean educational level can partly explain the
      higher prevalence of M detected in the workers on study with respect to the one
      described elsewhere on VDT workers and general population. The progression of the
      M seems not to be related to the professional and personal variables analyzed,
      but to depend on the natural evolution of M. Further studies are needed to
      confirm these preliminary data in larger groups of VDT workers.

PMID- 16805470
TI  - [Exposure to crystalline silica in the air during renovation of residential
      buildings].
AB  - Exposure to respirable cristalline silica dust during construction activities can
      cause silicosis and, in accordance with International Agency for Research on
      Cancer (IARC), even lung cancer. Among the different facets of construction,
      residential buildings are of particular interest because the lack of exposure
      data for workers employed. In this sector a dry sand-blasting of brick ceiling
      and renewal activities has been investigated. The survey has been carried out in
      a civil dwelling and 58 samples have been collected using the SKC aluminium
      cyclone and Door-Oliver plastic cyclone at flow-rate 2.2-1.7 l/min. The
      respirable dust samples were analysed by x-ray diffraction using NIOSH Method
      7500. Even if the results of this study should be considered preliminary, they
      showed SLC respirable concentrations even many time above TLV-TWA during a sand
      blasting activities and some times also during the other activities. Awaiting the
      correct classification from European Community, it would be desiderable that the
      workers would had appropriate information and prevention on the specific risks
      associated to the dust in the construction activities.

PMID- 16805471
TI  - [Descriptive statistics of occupational accidents during 2005 in the area of
      competency of the Occupational Health Unit FG/1].
AB  - During 2005, the Unit of Occupational Health of the Local Health Centre FG/1
      started to record accident at work. The results confirme "Industry" as the sector
      with the highest risk of accidents at work. Many accidents at work seem to be in
      relation with the insufficient use of D.P.I. or with the wrong use of D.P.I. The
      results point out the necessity of a better model to record data and in
      particular the data that describe what/how has the accident happened and the
      sector/subsector of workers. In order to continue this activity during the next
      years, it will be useful to control the trend.

PMID- 16805472
TI  - [Biological and chemical risks in haemodialysis centres].
AB  - Haemodialysis technique was introduced in 1965 for people afflicted to chronic
      renal insufficiency, permitting them to survive. The method purifies patient
      blood who is connected to the equipment by tubes. The equipment uses saline
      solutions and water and it operates by osmotic pressure and by filtration. In
      this paper biological and chemical occupational risks are analysed. Main
      biological risks are caused by haematic viruses such as HIV, HBV, HCV. Chemical
      risks are mainly caused by disinfection products such as acid, basic and saline
      solutions. Workers exposed to chemical and biological risks are nursing staff,
      doctors, assistants, maintenance men. The paper analyses these risks and it shows
      prevention and protection solutions to reduce significantly the risks. The
      S.Pre.S.A.L. (Prevention and Protection Service in Work Places) operators of ASL
      RMC (Health Local Agency of Rome) visited six haemodialysis centres situated in
      Rome in the ASL RMC territory. They verified the application of safety and
      healthy measures by use of a check list about risk assessment, the lay-out, the
      equipment, the preventive and protective measures and the application of law.
      Experimental data were organized in relation of legislative accomplishments and
      technical measures. The aim of our work was to improve workers' safety in the
      haemodialysis centres, proposing the better technical solutions to realise this
      objective.

PMID- 16805473
TI  - [Communication turned into prevention. The "European Week for the Safety and
      Health at Work": experience of the Italian Focal Point].
AB  - The constant focus on comprehensive quality of work and the promotion of an
      effective culture of prevention and communication, already indicated in the
      European Directives, gave new impetus to the strategy aimed at improving working
      conditions and workers' health. This study is aimed at identifying the successful
      factors of the European Week for Safety and Health at Work, an information and
      awareness campaign promoted by the European Agency for Safety and Health at Work
      based in Bilbao, through the analysis of the campaign's project and of the
      results achieved in Italy. The European Week, now at its 7th edition, represents
      a peerless opportunity to spread the culture of risk prevention and to raise
      awareness on the adoption of measures to improve workplaces, above all in small
      and medium enterprises. It is, furthermore, a valuable tool to communicate and
      disseminate messages and to promote good practices on occupational safety and
      health. ISPESL is the Italian Focal Point of the European Agency for Safety and
      Health at Work and has been supporting the organization of the European Week in
      Italy, since the first edition. It has been strongly committing itself to promote
      and disseminate information on the event, relying on its national network which
      operates throughout the national territory. The ISPESL web-site-
      http://www.ispesl.it--contains a web page dedicated to European Weeks, providing
      information on the campaign and on the related initiatives, on the materials, and
      on the main events taking place in Italy.

PMID- 16805474
TI  - [Perception of alcoholism risk in health workers: medical role in prevention and
      surveillance].
AB  - According to Italian laws (legge 125/01, art. 15, comma 1) about safety on
      workplaces, it's forbidden alcohol drinking and taking for health workers (art.
      8, comma 6, legge 5/06/2003 number 131) (e.g. anaesthesiology, surgery,
      radiology, nursing etc.). National alcoholism risk prevention program to assess
      number for year of accidents in health workplaces, is actually in progress leaded
      by Health Minister and Regional administration (e.g. Tuscany). Particularly,
      prevention program acts consist in comprehensive informations for health workers
      and their co- workers, about prevention and identification of alcoholism- related
      risks. To assess the size of alcohol problems in health workplaces, Occupational
      Health Medicine Institute of Second University of Naples is going to enrol 500
      subjects (200 nursing students, 200 Specialist Registrars of different areas, 100
      Consultants). Actually our population consists in 160 Specialist Registrars of
      different medical subjects (surgery, clinical and laboratory). To verify the
      importance of alcoholism risk perception, a not validated questionnaire was
      administrated. This original assessing instrument consists in 23 items with
      closed answers about demographic information, university, career, lifestyle,
      knowledge about rules taking alcoholic drinks. Results show a dangerous lack of
      information about alcohol health effects, even in Medical Specialist Registrars.

PMID- 16805475
TI  - [Modulation between alexithymic characteristic internal reality (Tas 20) and
      external coping in a group of artisans].
AB  - The Author examined a sample of 92 workers (74 M e 18 F) afferent's in study I in
      the time November 2005-April 2006 with the finality of study the caracteristic
      emotional/communicative with Test Tas-20. The results aren't with one score
      middle of 47.94 points with DS:15.53 and therefore the alexithimic caracteristic
      it's negative, with good expression of feelings, emotions, life styles. The
      middle age it's juvenile, 38.92 years with DS:10.45 and the subjects aren't
      marriage in the 60.86%. The organization of the work it's modulated, flexible and
      integrated and not of the type tayloristic/divided.

PMID- 16805476
TI  - [Perception of stress in the nursing profession: study of the behavior of s-IgA].
AB  - AIMS: To assess and compare self reported work stressors among emergency (PS) and
      medicine department (ME) nurses, and to investigate its relation with salivary
      IgA. METHODS: Fifty seven of 93 (61.2%) female PS and ME nurses participated in
      the study. The Italian version of NIOSH Job Stress Questionnaire was used to
      measure self perceived stress. ELISA methods were used to determine the salivary
      IgA. RESULTS: The scores of scales such as workload and conflict with co-workers
      were higher in PS (3.72 and 3.18) than in ME nurses (3.12 and 2.66). PS nurses
      had lower concentration rates of IgA (mean 123.3 microg/ml) than ME nurses (mean
      221.49 microg/ml). Significant inverse correlations were observed between the
      scores of workload and conflict with co-workers and log IgA (respectively r -0.27
      e -0.33, both p < 0.01). CONCLUSION: PS nurses showed significantly lower
      secretion rates of salivary IgA compared to ME nurses. Salivary IgA were
      inversely correlated with measured self reported work stressors.

PMID- 16805477
TI  - [Promotion of healthy lifestyles among shift workers].
AB  - A group of 50 shift workers were subjected to a programme of physical activity
      and balanced diet. The aim of this study was to promote a healthy lifestyle thus
      helping to prevent cardiovascular diseases, stress and to reduce alcohol and
      smoking habits.

PMID- 16805478
TI  - [Health risks associated with child labor: activities and proposals of WHO
      collaboration centers].
AB  - Child labour should be analyzed with regard to the main frameworks where it
      arises: particularly, the small family based enterprises in agricultural,
      hospitality and restaurateurs' sectors play a leading role. In these contexts the
      child can underestimate the risks related to the carried out work activity and
      assimilate the work background to the family background. In spite of the national
      thorough regulations on child labour, the network of WHO Collaborating Centres is
      working to develop a common awareness in order to evaluate, communicate and
      prevent the occupational health and safety risks for children, at national and
      international level.

PMID- 16805479
TI  - [Communication of chemical and carcinogen risk at refinery maintenance
      companies].
AB  - This short paper reports a communication experience about chemical/carcinogen
      risk aimed to characterize and to document different occasions and several ways
      of exposure of the workers employed in maintenance companies in a petrochemical
      factory. We utilized different source of information: from risk assessment
      document (VR) of the petrochemical plant and from job sheets of the companies on
      contracts of maintenance. Working this way it has been possible to create a
      database which includes information about chemical agents, length and the way of
      exposure for every worker. This database allows to improve the level of knowledge
      of the Occupational Health Doctors, Professionals and of the workers, moreover it
      is useful to take note of quality and way of exposure in the VR document.

PMID- 16805480
TI  - [Acute pneumonia caused by aspiration of hydrocarbons in a fire-eater].
AB  - Accidental aspiration of fuel in fire eaters can cause an acute chemical
      pneumonitis known as 'fire-eater's pneumonia". We report a case in a 29 year-old
      fire-eater. Six hours after aspiration of kerosene, he developed fever up to 39,5
      degrees C, dyspnea, cough and chest pain. Chest radiograph showed infiltrates in
      the middle and lower parts of the lungs and left pleural effusion. He was treated
      with an antibiotic and antipiretic therapy and then with corticosteroids. The
      acute stage lasted four weeks and the patient recovered without sequelae within 3
      months. Hazard related to main fuels used for fire eating is discussed.

PMID- 16805481
TI  - Infrared detection of HO2 and HO3 radicals in water ice.
AB  - Infrared spectroscopy has been used to detect HO(2) and HO(3) radicals in H(2)O +
      O(2) ice mixtures irradiated with 0.8 MeV protons. In these experiments, HO(2)
      was formed by the addition of an H atom to O(2) and HO(3) was formed by a similar
      addition of H to O(3). The band positions observed for HO(2) and HO(3) in H(2)O
      ice are 1142 and 1259 cm(-1), respectively, and these assignments were confirmed
      with (18)O(2). HO(2) and HO(3) were also observed in irradiated H(2)O + O(3) ice
      mixtures, as well as in irradiated H(2)O(2) ice. The astronomical relevance of
      these laboratory measurements is discussed.

PMID- 16805482
TI  - Vibrational and vibronic processes in coherent 2D resonance Raman spectroscopy.
AB  - Coherent 2D resonance Raman spectroscopy is a multidimensional technique that is
      capable of separating and sorting peaks that appear heavily congested and
      disordered in conventional 1D spectra. It can sort rovibrational peaks according
      to rotational and vibrational quantum number, vibrational sequence, and
      rotational selection rule. New results suggest that pattern recognition methods
      can also be used to determine whether the highly detailed rovibrational
      information is coming from the ground electronic state or the excited electronic
      state. This capability is demonstrated using experimental results from I(2) and
      C(2).

PMID- 16805483
TI  - Electron transfer in self-assembled orthogonal structures.
AB  - Two new molecular dyads, comprising pyrromethene (bodipy) and 2,2':6',2"
      terpyridine (terpy) subunits, have been synthesized and fully characterized.
      Absorption and fluorescence spectral profiles are dominated by contributions from
      the bodipy unit. Zinc(II) cations bind to the vacant terpy ligand to form both
      1:1 and 1:2 (cation:ligand) complexes, as evidenced by X-ray structural data, NMR
      and spectrophotometric titrations. Attachment of the cations is accompanied by a
      substantial decrease in fluorescence from the bodipy chromophore due to
      intramolecular electron transfer across the orthogonal structure. At low
      temperature, nuclear tunneling occurs and the rate of electron transfer is
      essentially activationless. However, activated electron transfer is seen at
      higher temperatures and allows calculation of the corresponding reorganization
      energy and electronic coupling matrix element. In both cases, charge
      recombination is faster than charge separation.

PMID- 16805484
TI  - Photoinduced single- versus double-bond torsion in donor-acceptor-substituted
      trans-stilbenes.
AB  - The electronic absorption and fluorescence spectra, quantum yields for
      fluorescence (Phi(f)) and trans --> cis photoisomerization (Phi(tc)), and
      fluorescence lifetimes of trans-4-(N-arylamino)-4'-cyanostilbenes (2H, 2Me, 2OM,
      2CN, and 2Xy with aryl = phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-cyanophenyl,
      and 2,5-dimethylphenyl, respectively), trans-4-(N-methyl-N-phenylamino)-4'
      cyanostilbene (2MP), trans-4-(N,N-diphenylamino)-4'-cyanostilbene (2PP), trans-4
      (N-methyl-N-phenylamino)-4'-nitrostilbene (3MP), and three ring-bridged analogues
      2OMB, 2MPB, and 3MPB are reported. Whereas fluorescence and torsion of the
      central double bond account for the excited decay of the majority of these donor
      acceptor substituted stilbenes in both nonpolar and polar solvents (i.e., Phi(f)
      + 2Phi(tc) approximately 1), exceptions are observed for 2OM, 3MP, and 3MPB in
      solvents more polar than THF and for 2Me and 2MP in acetonitrile as a result of
      the formation of a weakly fluorescent and isomerization-free twisted
      intramolecular charge transfer (TICT) state (i.e., Phi(f) + 2Phi(tc) << 1). The
      TICT state for 2OM, 2Me, and 2MP results from the torsion of the stilbenyl
      anilino C-N single bond, but the torsion of the styryl-anilino C-C bond is more
      likely to be responsible for the TICT state formation of 3MP and 3MPB. In
      conjunction with the behavior of aminostilbenes 1, a guideline based on the
      values of Phi(f) and Phi(tc) for judging the importance of a TICT state for trans
      stilbenes is provided. Accordingly, the TICT state formation is unimportant for
      the excited decay of trans-4-(N,N-dimethylamino)-4'-cyanostilbene (DCS). In
      contrast, our results support the previously proposed TICT state for trans-4-(N,N
      dimethylamino)-4'-nitrostilbene (DNS).

PMID- 16805485
TI  - Terahertz vibration-rotation-tunneling spectroscopy of the ammonia dimer:
      characterization of an out of plane vibration.
AB  - The terahertz vibration-rotation-tunneling (VRT) spectrum of the ammonia dimer
      (NH(3))(2) has been measured between ca. 78.5 and 91.9 cm(-1). The dipole-allowed
      transitions are separated into three groups that correspond to the 3-fold
      internal rotation of the NH(3) subunits. Transitions have been assigned for VRT
      states of the A-A (ortho-ortho) combinations of NH(3) monomer states. The
      spectrum is further complicated by strong Coriolis interactions. K = 0 <-- 0, K =
      1 <-- 0, K = 0 <-- 1, and K = 1 <-- 1 progressions have been assigned. The band
      origins, rotational constants, asymmetry doubling, centrifugal distortion, and
      Coriolis coupling constant have been determined from the fit to an effective
      Hamiltonian. These VRT transitions are tentatively assigned to an out of plane
      vibration with a K = 0 state at 89.141305(47) cm(-1), and a K = 1 state at
      86.77785(9) cm(-1).

PMID- 16805486
TI  - Matrix isolation infrared spectroscopic and theoretical study of nickel,
      palladium, and platinum nitrous oxide complexes.
AB  - Binary nickel, palladium, and platinum nitrous oxide complexes Ni(NNO)x, Pd(NNO)x
      (x = 1, 2), and PtNNO have been produced by the reactions of laser-evaporated
      metal atoms with nitrous oxide in solid argon. The complexes were identified on
      the basis of isotopically substituted infrared absorptions as well as theoretical
      frequency calculations. These complexes were characterized to have structures
      with the terminal N atom of N(2)O bound to the metal atoms. The MNNO complexes
      are photosensitive and rearrange to OMNN or MO + N(2) upon ultraviolet-visible
      irradiation.

PMID- 16805487
TI  - Intramolecular vibrational redistribution in the vibrational predissociation
      dynamics of He-I2.
AB  - The intramolecular vibrational redistribution (IVR) process is investigated in
      wave packet simulations of the vibrational predissociation dynamics of He
      I(2)(B,upsilon') in the region of high upsilon' levels, upsilon' = 35-65. The
      simulations indicate that for upsilon' < or = 45 the dynamics is dominated by
      direct predissociation, whereas for higher upsilon' levels the onset of IVR
      appears and becomes increasingly important. The IVR process occurs via coupling
      of the initial state in the upsilon' manifold to intermediate long-lived
      resonances belonging to the lower upsilon < upsilon' vibrational manifolds. The
      IVR dynamics manifests itself in multiexponential behavior and oscillations in
      the time-dependent population curves associated with the He-I(2)(B,upsilon')
      initial state, the He-I(2)(B,upsilon < upsilon') intermediate complexes, and the
      final product states. The population curves corresponding to the upsilon'- 1
      intermediate resonances located below the He + I(2)(B,upsilon'-1,j=0)
      dissociation limit are analyzed. It is found that initial population is
      transferred to all the intermediate resonance states considered, including those
      more separated in energy from the initial one. The results obtained for
      population transfer between the initial and the intermediate states can be
      explained by the intensity of the matrix elements coupling the initial and the
      intermediate resonances, in combination with the Rabi's formula for population
      exchange between two coupled states.

PMID- 16805488
TI  - Photoelectron imaging study of the effect of monohydration on O2 -
      photodetachment.
AB  - The photodetachment of the O(2)(-).H(2)O cluster anion at 780 and 390 nm is
      investigated in comparison with O(2)(-) using photoelectron imaging spectroscopy.
      Despite the pronounced shift in the photoelectron spectra, the monohydration has
      little effect on the photoelectron angular distributions: for a given wavelength
      and electron kinetic energy (eKE) range, the O(2)(-).H(2)O angular distributions
      are quantitatively similar to those for bare O(2)(-). This observation confirms
      that the excess electron in O(2)(-).H(2)O retains the overall character of the
      2ppi(g) HOMO of O(2)(-). The presence of H(2)O does not affect significantly the
      partial wave composition of the photodetached electrons at a given eKE. An
      exception is observed for slow electrons, where O(2)(-).H(2)O exhibits a faster
      rise in the photodetachment signal with increasing eKE, as compared to O(2)(-).
      The possible causes of this anomaly are (i) the long-range charge-dipole
      interaction between the departing electron and the neutral O(2).H(2)O skeleton
      affecting the slow-electron dynamics; and (ii) the s wave contributions to the
      photodetachment, which are dipole-forbidden for pi(g)(-1) transitions in O(2)(-),
      but formally allowed in O(2)(-).H(2)O due to lower symmetry of the cluster anion
      and the corresponding HOMO.

PMID- 16805489
TI  - Microwave spectra, ab initio calculations, and r0 structural parameters for
      (methylamino)thiophosphoryl difluoride.
AB  - The microwave spectra of (methylamino)thiophosphoryl difluoride,
      CH(3)NHP(=S)F(2), and two deuterated species, CH(3)NDP(=S)F(2) and
      CD(3)NHP(=S)F(2), have been investigated in the region from 26.5 to 39.0 GHz. The
      rotational constants of the ground vibrational state have been determined and
      have been shown to be only consistent with the trans conformer (CH(3) group
      antiperiplanar to the P=S bond) with C(s) symmetry. The a-type R branch
      transitions have been assigned for the trans conformer for the three isotopomers
      on the basis of the rigid rotor model. Near-trans and near-cis forms without
      molecular planes of symmetry are predicted by all ab initio calculations with the
      near-trans form being more stable. However, the double-well potentials governing
      the interchange between the two enantiomeric near-trans as well as the two near
      cis forms are too shallow to accommodate the zero-point energies of the nu(24)
      asymmetric torsion. Thus, the trans conformation with C(s) symmetry may be more
      accurate in explaining the microwave experimental data. The "adjusted" r(0)
      structural parameters have been obtained by systematically adjusting the ab
      initio MP2(full)/6-311+G(d,p) structure of the trans conformer with C(s) symmetry
      to fit the microwave rotational constants. The determined heavy atom distances
      are r(C-N) = 1.459(5), r(P-N) = 1.621(5), r(P=S) = 1.879(5), and r(P-F) =
      1.550(5) A, and the heavy atom angles are angleCNP = 124.7(5) degrees , angleNPS
      = 118.3(5) degrees , angleNPF = 103.2(5) degrees , angleFPS = 117.0(5) degrees ,
      and angleFPF = 94.6(5) degrees . The adjusted r(0) parameters have also been
      obtained for aminodifluorophosphine, H(2)NPF(2), with a slightly pyramidal 
      PNH(2) moiety. The results indicate that the previously reported short distance
      of 0.981(5) A for the N-H(o)(outer) bond from the microwave study is too short,
      and the adjusted r(0) value of 1.007(3) A is obtained from the combined data.
      Adjusted r(0) parameters are also reported for (dimethylamino)difluorophosphine,
      (CH(3))(2)NPF(2), with C(s) symmetry with the PNC(2) portion of the molecule
      being planar. The previously reported C-H distances from the electron diffraction
      study are too long, and the anglePNC(i) and angleC(o)NC(i) angles are also found
      to be in error. These results provide a reasonable explanation why the microwave
      and electron diffraction results differ for the structures of these latter two
      molecules.

PMID- 16805490
TI  - s-trans-1,3-butadiene and isotopomers: vibrational spectra, scaled quantum
      chemical force fields, fermi resonances, and C-H bond properties.
AB  - Quadratic quantum-chemical force fields have been determined for s-trans-1,3
      butadiene using B3LYP and MP2 methods. Basis sets included 6-311++G, cc-pVTZ, and
      aug-cc-pVTZ. Scaling of the force fields was based on frequency data for up to 11
      isotopomers, some of these data being original. A total of 18 scale factors were
      employed, with, in addition, an alteration to one off-diagonal force constant in
      the A(u) species. MP2 calculations without f functions in the basis perform badly
      in respect of out-of-plane bending mode frequencies. Centrifugal distortion
      constants and harmonic contributions to vibration-rotation constants (alphas)
      have been calculated. Existing experimental frequency data for all isotopomers
      are scrutinized, and a number of reassignments and diagnoses of Fermi resonance
      made, particularly in the nu(CH) region. The three types of CH bond in butadiene
      were characterized in terms of bond length and isolated CH stretching frequency,
      the latter reflecting data in the nu(CD) region. Broad agreement was achieved
      with earlier results from local mode studies. Differences in CH bond properties
      resemble similar differences in propene. A simplified sample setup for recording
      FT-Raman spectra of gases was applied to four isotopomers of butadiene.

PMID- 16805491
TI  - Far-infrared spectroscopy of small neutral silver clusters.
AB  - The vibrational spectra of Ag(3) and Ag(4) are recorded in the far-infrared
      between 100 and 220 cm(-1) using multiple photon dissociation spectroscopy of
      their complexes with Ar atoms. For Ag(3)-Ar two IR active bands are found at 113
      and 183 cm(-1), for Ag(4)-Ar one band at 163 cm(-1) and very weak IR activity at
      193 cm(-1) are observed. This, together with recent theoretical studies, allows
      for a reassignment of the controversial vibrational data reported earlier for the
      bare Ag(3) cluster. The influence of the number of Ar atoms in the complexes on
      the frequency of the IR active modes is found to be minor. However, the low
      frequency IR-active band of Ag(3) shifts with increasing Ar coverage from 113 cm(
      1) for Ag(3)-Ar to about 120 cm(-1) for Ag(3)-Ar(4), the value known for Ag(3)
      embedded in rare gas matrices.

PMID- 16805492
TI  - Experimental and theoretical studies on carbon-nitrogen clusters C2nN7-.
AB  - C(2n)N7(-) cluster ions are produced by laser ablating on the K(3)[Fe(CN)6]
      sample. DFT calculations have been performed for these cluster anions. Various
      isomeric structures of these clusters are optimized and their energies are
      compared to find the most stable isomers. The most stable structure for C8N7(-)
      is similar to that of adenine by theoretical calculation, which is in agreement
      with the collision-induced dissociation (CID) experimental results. With the
      increasing even numbers of C atoms from 8 to 16, the N atoms in the double-ring
      structure are gradually substituted by C atoms from the six-membered ring to the
      five-membered ring. All these C(2n)N7(-) (n = 3-9) clusters exhibit planar
      aromatic characters. The energy difference and incremental binding energy
      analyses show that C(2n)N7(-) (n = 4-8) clusters are more stable than C6N7(-) and
      C18N7(-), which are consistent with the observed mass spectrum.

PMID- 16805493
TI  - Formation of trimer and dimer radical cations of methyl-substituted benzenes in
      gamma-irradiated low-temperature matrices.
AB  - Dimer and trimer radical cations of benzene, toluene, and xylenes were produced
      selectively after gamma-irradiation in low-temperature 2-methylpentane matrices
      with electron scavengers: oxygen (O(2)) and sec-butyl chloride (sec-BuCl). The
      charge resonance (CR) band of the trimer radical cation (M(3)(+)) produced via
      the corresponding dimer radical cation (M(2)(+)) is clearly seen in the solution
      containing O(2) as the temperature increases over a range from 80 to 90 K. In o
      xylene solution, a fairly strong and distinct M(3)(+) CR absorption is observed;
      this is due to the large M(3)(+)/M(2)(+) relative extinction coefficient. All
      benzene derivatives show an equilibrium between dimer and trimer radical cations
      at approximately 90 K; however, the equilibrium constants of toluene and the
      xylenes are considerably lower than that of benzene. Formation of the trimer
      radical cation is inhibited in sec-BuCl, which has commonly been used as a low
      temperature optical matrix for producing cationic species. An ab initio DFT
      method is applied to predict the geometry of M(3)(+), giving "slipped sandwich"
      (for benzene, m-xylene, and p-xylene) and "slipped fan-shaped" (toluene and o
      xylene) structures as the most plausible geometries. The experimentally observed
      spectroscopic parameters reflect well those predicted by TD-DFT calculation based
      on geometry, suggesting strong dependence of the geometry of M(3)(+) on
      substitution patterns. This is the first report not only of direct spectroscopic
      observation of aromatic trimer radical cations in the condensed phase but also on
      the quantitative analysis of their equilibria.

PMID- 16805495
TI  - Diffusivity of asphaltene molecules by fluorescence correlation spectroscopy.
AB  - Using fluorescence correlation spectroscopy (FCS) we measure the translational
      diffusion coefficient of asphaltene molecules in toluene at extremely low
      concentrations (0.03-3.0 mg/L): where aggregation does not occur. We find that
      the translational diffusion coefficient of asphaltene molecules in toluene is
      about 0.35 x 10(-5) cm(2)/s at room temperature. This diffusion coefficient
      corresponds to a hydrodynamic radius of approximately 1 nm. These data confirm
      previously estimated size from rotational diffusion studied using fluorescence
      depolarization. The implication of this concurrence is that asphaltene molecular
      structures are monomeric, not polymeric.

PMID- 16805494
TI  - Unusual photochemical C-N bond cleavage in the novel methyl 2-chloro-3-methyl-2H
      azirine-2-carboxylate.
AB  - The structure, preferred conformers, vibrational spectrum, and photochemical
      behavior of the novel azirine, methyl 2-chloro-3-methyl-2H-azirine-2-carboxylate
      (MCMAC) were investigated in low-temperature matrixes and in the neat solid
      amorphous state by infrared spectroscopy and quantum-chemical calculations. Two
      conformers of the compound were observed in argon, krypton, and xenon matrixes,
      in agreement with the DFT(B3LYP)/6-311++G(d,p) and MP2/6-311++G(d,p) theoretical
      calculations. Both conformers were found to exhibit the carboxylic ester group in
      the cis conformation, differing in the arrangement defined by the O=C-C-Cl
      dihedral angle (cis and trans, for Ct and Cc forms, respectively). The Ct
      conformer was found to be the most stable conformer in the gaseous phase as well
      as in both argon and krypton matrixes, whereas the more polar Cc conformer became
      the most stable form in the xenon matrix and in the neat solid amorphous phase.
      In situ broadband UV (lambda > 235 nm) excitation of matrix-isolated MCMAC led to
      azirine ring C-C and C-N bond cleavages, the latter process corresponding to the
      most efficient reaction channel. The photochemical cleavage of the C-N bond had
      never been previously observed in the case of aliphatic 2H-azirines. Two electron
      withdrawing substituents (methoxycarbonyl group and chlorine atom) are connected
      to the azirine ring in the novel MCMAC azirine. The simultaneous presence of
      these two groups accelerates intersystem crossing toward the triplet state where
      cleavage of the C-N bond takes place. The primary photoproducts resulting from
      the C-N and C-C ring-opening reactions were also found to undergo further
      photochemical decarbonylation or decarboxylation reactions.

PMID- 16805496
TI  - Acetone adsorption on ice surfaces in the temperature range T = 190-220 K:
      evidence for aging effects due to crystallographic changes of the adsorption
      sites.
AB  - The rate and thermodynamics of the adsorption of acetone on ice surfaces have
      been studied in the temperature range T = 190-220 K using a coated-wall flow tube
      reactor (CWFT) coupled with QMS detection. Ice films of 75 +/- 25 microm
      thickness were prepared by coating the reactor using a calibrated flow of water
      vapor. The rate coefficients for adsorption and desorption as well as adsorption
      isotherms have been derived from temporal profiles of the gas phase concentration
      at the exit of the flow reactor together with a kinetic model that has recently
      been developed in our group to simulate reversible adsorption in CWFTs (Behr, P.;
      Terziyski, A.; Zellner, R. Z. Phys. Chem. 2004, 218, 1307-1327). It is found that
      acetone adsorption is entirely reversible; the adsorption capacity, however,
      depends on temperature and decreases with the age of the ice film. The aging
      effect is most pronounced at low acetone gas-phase concentrations (< or = 2.0 x
      10(11) molecules/cm(3)) and at low temperatures. Under these conditions, acetone
      is initially adsorbed with a high rate and high surface coverage that, upon
      aging, both become lower. This effect is explained by the existence of initially
      two adsorption sites (1) and (2), which differ in nature and number density and
      for which the relative fractions change with time. Using two-site dynamic
      modeling, the rate coefficients for adsorption (k(ads)) and desorption (k(des))
      as well as the Langmuir constant (K(L)) and the maximum number of adsorption
      sites (c(s,max)), as obtained for the adsorption of acetone on sites of types (1)
      and (2) in the respective temperature range, are k(ads)(1) = 3.8 x 10(-14) T(0.5)
      cm(3) s(-1), k(des)(1) = 4.0 x 10(11) exp(-5773/T) s(-1), K(L) (1) = 6.3 x 10(
      25) exp(5893/T) cm(3), c(s,max)(1) < or = 10(14) cm(-2) and k(ads)(2) = 2.9 x 10(
      15) T(0.5) cm(3) s(-1), k(des)(2) = 1.5 x 10(7) exp(-3488/T) s(-1), K(L)(2) = 5.0
      x 10(-22) exp(3849/T) cm(3), c(s,max)(2) = 6.0 x 10(14) cm(-2), respectively. On
      the basis of these results, the adsorption of acetone on aged ice occurs
      exclusively on sites of type (2). Among the possible explanations for the time
      dependent two-site adsorption behavior, i.e., crystallographic differences,
      molecular or engraved microstructures, or a mixture of the two, we tentatively
      accept the former, i.e., that the two adsorption sites correspond to cubic (1,
      I(c)) and hexagonal (2, I(h)) sites. The temporal change of I(c) to I(h) and,
      hence, the time constants of aging are consistent with independent information in
      the literature on these phase changes.

PMID- 16805497
TI  - Crystallization of aqueous inorganic-malonic acid particles: nucleation rates,
      dependence on size, and dependence on the ammonium-to-sulfate ratio.
AB  - Using an electrodynamic balance, we determined the relative humidity (RH) at
      which aqueous inorganic-malonic acid particles crystallized, with ammonium
      sulfate ((NH(4))(2)SO(4)), letovicite ((NH(4))(3)H(SO(4))(2)), or ammonium
      bisulfate (NH(4)HSO(4)) as the inorganic component. The results for
      (NH(4))(2)SO(4)-malonic acid particles and (NH(4))(3)H(SO(4))(2)-malonic acid
      particles show that malonic acid decreases the crystallization RH of the
      inorganic particles by less than 7% RH when the dry malonic acid mole fraction is
      less than 0.25. At a dry malonic acid mole fraction of about 0.5, the presence of
      malonic acid can decrease the crystallization RH of the inorganic particles by up
      to 35% RH. For the NH(4)HSO(4)-malonic acid particles, the presence of malonic
      acid does not significantly modify the crystallization RH of the inorganic
      particles for the entire range of dry malonic acid mole fractions studied; in all
      cases, either the particles did not crystallize or the crystallization RH was
      close to 0% RH. Size dependent measurements show that the crystallization RH of
      aqueous (NH(4))(2)SO(4) particles is not a strong function of particle volume.
      However, for aqueous (NH(4))(2)SO(4)-malonic acid particles (with dry malonic
      acid mole fraction = 0.36), the crystallization RH is a stronger function of
      particle volume, with the crystallization RH decreasing by 6 +/- 3% RH when the
      particle volume decreases by an order of magnitude. To our knowledge, these are
      the first size dependent measurements of the crystallization RH of
      atmospherically relevant inorganic-organic particles. These results suggest that
      for certain organic mole fractions the particle size and observation time need to
      be considered when extrapolating laboratory crystallization results to
      atmospheric scenarios. For aqueous (NH(4))(2)SO(4) particles, the homogeneous
      nucleation rate data are a strong function of RH, but for aqueous (NH(4))(2)SO(4)
      malonic acid particles (with dry organic mole fraction = 0.36), the rates are not
      as dependent on RH. The homogeneous nucleation rates for aqueous (NH(4))(2)SO(4)
      particles were parametrized using classical nucleation theory, and from this
      analysis we determined that the interfacial surface tension between the
      crystalline ammonium sulfate critical nucleus and an aqueous ammonium sulfate
      solution is between 0.053 and 0.070 J m(-2).

PMID- 16805498
TI  - Spectroscopy of growing and evaporating water droplets: exploring the variation
      in equilibrium droplet size with relative humidity.
AB  - We demonstrate that the thermodynamic properties of a single liquid aerosol
      droplet can be explored through the combination of a single-beam gradient force
      optical trap with Raman spectroscopy. A single aqueous droplet, 2-6 microm in
      radius, can be trapped in air indefinitely and the response of the particle to
      variations in relative humidity investigated. The Raman spectrum provides a
      unique fingerprint of droplet composition, temperature, and size. Spontaneous
      Raman scattering is shown to be consistent with that from a bulk phase sample,
      with the shape of the OH stretching band dependent on the concentration of sodium
      chloride in the aqueous phase and on the polarization of the scattered light.
      Stimulated Raman scattering at wavelengths commensurate with whispering gallery
      modes is demonstrated to provide a method for determining the size of the trapped
      droplet with nanometer precision and with a time resolution of 1 s. The
      polarization dependence of the stimulated scatter is consistent with the
      dependence observed for the spontaneous scatter from the droplet. By
      characterizing the spontaneous and stimulated Raman scattering from the droplet,
      we demonstrate that it is possible to measure the equilibrium size and
      composition of an aqueous droplet with variation in relative humidity. For this
      benchmark study we investigate the variation in equilibrium size with relative
      humidity for a simple binary sodium chloride/aqueous aerosol, a typical
      representative inorganic/aqueous aerosol that has been studied extensively in the
      literature. The measured equilibrium sizes are shown to be in excellent agreement
      with the predictions of Kohler theory. We suggest that this approach could
      provide an important new strategy for characterizing the thermodynamic properties
      and kinetics of transformation of aerosol particles.

PMID- 16805499
TI  - Toward electron encapsulation: polynitrile approach.
AB  - This study seeks an answer to the following question: Is it possible to design a
      supramolecular cage that would "solvate" the excess electron in the same fashion
      in which several solvent molecules do that cooperatively in polar liquids? Two
      general strategies are outlined for this "electron encapsulation", viz. electron
      localization using polar groups arranged on the (i) inside of the cage or (ii)
      outside of the cage. The second approach is more convenient from the synthetic
      standpoint, but it is limited to polynitriles. We demonstrate, experimentally and
      theoretically, that this second approach faces a problem: the electron attaches
      to the nitrile groups, forming molecular anions with bent C-C-N fragments.
      Because the energy cost of this bending is high, for dinitrile anions in n
      hexane, the binding energies for the electron are low and, for mononitriles,
      these binding energies are lower still, and the entropy of electron attachment is
      anomalously small. Density functional theory modeling of electron trapping by
      mononitriles in n-hexane suggests that the solute molecules substitute for the
      solvent molecules at the electron cavity, "solvating" the electron by their
      methyl groups. We argue that such species would be more correctly viewed as
      multimer radical anions in which the electron density is shared (mainly) between
      C 2p orbitals in the solute/solvent molecules, rather than cavity electrons. The
      way in which the excess electron density is shared by such molecules is similar
      to the way in which this sharing occurs in large di- and polynitrile anions, such
      as 1,2,4,5,7,8,10,11-octacyanocyclododecane(-). Only in this sense is the
      electron encapsulation possible. The work thus reveals limitations of the concept
      of "solvated electron" for organic liquids: it is impossible to draw a clear line
      between such species and a certain class of radical anions.

PMID- 16805500
TI  - Characterization of cationic diarylethene by electron spin resonance and
      absorption spectra-ratio of open/closed-ring isomers.
AB  - Electrochemical cyclization/cycloreversion reactions of a diarylethene, 1,2-bis(3
      methyl-2-thienyl)perfluorocyclopentene, are examined experimentally by electron
      spin resonance (ESR) and absorption spectra. To understand the ESR spectrum, the
      hyperfine coupling constants are calculated by the density functional theory
      (DFT) with the B3LYP exchange-correlation functional. The averaged values of the
      hyperfine coupling constants are approximated by imposing the C(2) symmetry on
      the structure of the diarylethene. We found that the spectral width of the ESR is
      significantly different between the open- and closed-ring isomers. This is due to
      the difference in the pi-conjugation between two isomers. The ESR spectral width
      analysis could, thus, be used to identify the isomerization of the radical
      species, which involve the change of the pi-conjugation. The experimentally
      observed spectrum is found to be the mixture of the open- and closed-ring isomers
      of the diarylethene. The excitation energies of the cationic diarylethenes are
      further identified by the SAC-CI calculations.

PMID- 16805501
TI  - TD-DFT investigation of the UV spectra of pyranone derivatives.
AB  - The UV absorption spectra of more than 80 substituted coumarins and chromones
      have been investigated with the PCM-TD-DFT theoretical scheme using three hybrid
      functionals (O3LYP, B3LYP, and PBE0) and taking into account methanol or ethanol
      solvation effects. For most of the studied derivatives, there are at least two
      allowed excited states presenting a strong oscillator strength in the UV region.
      The first allowed excitation is associated to a HOMO-LUMO transition whereas the
      second corresponds to a transition from the HOMO-1 to the LUMO. Both involve a
      charge transfer from the benzenic cycle to the pyranone moiety. Statistically
      treating the PBE0 results allows a prediction of the lambda(max) with small
      standard deviations: in methanol, 6 nm (0.07 eV) for the first excitation
      (lambda(max)(1)) and 5 nm (0.08 eV) for the second one (lambda(max)(2)), whereas
      in ethanol 6 nm (0.08 eV) for (lambda(max)(1)) and 6 nm (0.13 eV) for
      (lambda(max)(2)).

PMID- 16805502
TI  - Oxidation pattern of small silicon oxide clusters: structures and stability of
      Si6On (n = 1-12).
AB  - We have performed systematic ab initio calculations to study the structures and
      stability of Si(6)O(n)() clusters (n = 1-12) in order to understand the oxidation
      process in silicon systems. Our calculation results show that oxidation pattern
      of the small silicon cluster, with continuous addition of O atoms, extends from
      one side to the entire Si cluster. Si atoms are found to be separated from the
      pure Si cluster one-by-one by insertion of oxygen into the Si-O bonds. From
      fragmentation energy analyses, it is found that the Si-rich clusters usually
      dissociate into a smaller pure Si clusters (Si(5), Si(4), Si(3), or Si(2)), plus
      oxide fragments such as SiO, Si(2)O(2), Si(3)O(3), Si(3)O(4), and Si(4)O(5). We
      have also studied the structures of the ionic Si(6)O(n)(+/-) (n = 1-12) clusters
      and found that most of ionic clusters have different lowest-energy structures in
      comparison with the neutral clusters. Our calculation results suggest that
      transformation Si(6)O(n)+(a) + O --> Si(6)O(n+1)+(a) should be easier.

PMID- 16805503
TI  - Effect of para-substituents and solvent polarity on the formation of
      triphenylboroxine.amine adducts.
AB  - Density functional theory (B3LYP//6-311+G) calculations including Poisson
      Boltzmann implicit solvent and NMR were used to study the formation of a series
      of para-substituted triphenylboroxine.amine adducts with respect to their
      phenylboronic acid monomers and free amine in solution. Our calculations suggest
      that the intermediate prior to forming trimer.amine is a dimer.amine adduct.
      Formation of dimer.amine can proceed via two pathways. Electron-donating
      substituents favor dimerization of two monomers before addition of the amine, and
      electron-withdrawing substituents favor formation of a monomer.amine adduct
      before addition of the second monomer. We also find that pi-electron acceptors
      destabilize formation of the dimer and trimer with respect to its monomers.
      Electron-withdrawing substituents favor adduct formation. Adduct formation is
      enthalpically stabilized by increasing the polarity of the solvent but
      differential solubility of the monomer compared to trimer.amine also has an
      effect on the equilibrium constant.

PMID- 16805504
TI  - Bromine-loss and hydrogen-loss dissociations in low-lying electronic states of
      the CH3Br+ ion studied using multiconfiguration second-order perturbation theory.
AB  - Complete active space self-consistent field (CASSCF) and multiconfiguration
      second-order perturbation theory (CASPT2) calculations with an ANO-RCC basis were
      performed for the 1(2)A', 1(2)A", 2(2)A', and 2(2)A" states of the CH3Br+ ion.
      The 1(2)A' state is predicted to be the ground state. The 2(2)A' state is
      predicted to be a bound state. The adiabatic and vertical excitation energies and
      the relative energies at the molecular geometry were calculated, and the
      energetic results for 2(2)A' and 2(2)A" are in reasonable agreement with the
      experimental data. Potential energy curves (PECs) for Br-loss and H-loss
      dissociations from the four C(s) states were calculated at the CASPT2//CASSCF
      level and the electronic states of the CH3(+) and CH2Br(+) ions as the
      dissociation products were determined by checking the relative energies and
      geometries of the asymptote products along the PECs. In the Br-loss dissociation,
      the 1(2)A', 1(2)A", and 2(2)A' states correlate with CH3(+) (X1A1') and the
      2(2)A" state correlates with CH3(+) (1(3)A"). The energy increases monotonically
      with the R(C-Br) value along the four Br-loss PECs. In the H-loss dissociation
      the 1(2)A', 1(2)A", 2(2)A', and 2(2)A" states correlate with the X(1)A(1),
      1(3)A", 1(3)A', and 1(1)A" states (1(3)A' lying above 1(1)A") of CH2Br(+),
      respectively. Along the 2(2)A" H-loss PEC there is an energy barrier and the
      CASSCF wave functions at large R(C-H) values have shake-up ionization character.
      Along the 2(2)A' H-loss PEC there are an energy barrier and a minimum. At the end
      of the present paper we present a comprehensive review on the electronic states
      and the X-loss and H-loss dissociations of the CH(3)X(+) (X = F, Cl, and Br) ions
      on the basis of our previous studies and the present study.

PMID- 16805505
TI  - Density functional theory/time-dependent DFT studies on the structures, trend in
      DNA-binding affinities, and spectral properties of complexes [Ru(bpy)2(p-R
      pip)]2+ (R = -OH, -CH3, -H, -NO2).
AB  - Studies on the electronic structures and trend in DNA-binding affinities of a
      series of Ru(II) complexes [Ru(bpy)2(p-R-pip)]2+ (bpy = 2,2-bipyridine; pip = 2
      phenylimidazo[4,5-f] [1,10]-phenanthroline; R = -OH, -CH3, -H, -NO2) 1-4 have
      been carried out, using the density functional theory (DFT) at the B3LYP/LanL2DZ
      level. The electronic absorption spectra of these complexes were also
      investigated using time-dependent DFT (TDDFT) at the B3LYP//LanL2DZ/6-31G level.
      The computational results show that the substituents on the parent ligand (pip)
      have a significant effect on the electronic structures of the complexes, in
      particular, on the energies of the lowest unoccupied molecular orbital (LUMO) and
      near some unoccupied molecular orbitals (LUMO+x, x = 1-4). With the increase in
      electron-withdrawing ability of the substituent in this series, the LUMO+x (x = 0
      4) energies of the complexes are substantially reduced in order, for example,
      epsilon(LUMO)(1) approximately epsilon(LUMO)(2) > epsilon(LUMO)(3) >
      epsilon(LUMO)(4), whereas the pi-component populations of the LUMO+x (x = 0-4)
      are not substantially different. Combining the consideration of the bigger steric
      hindrance of complex 2, the trend in DNA-binding affinities (K(b)) of the
      complexes, that is, K(b)(2) < K(b)(1) < K(b)(3) < K(b)(4) can be reasonably
      explained. In addition, the experimental singlet metal-to-ligand charge transfer
      ((1)MLCT) spectra of these complexes can be well simulated and discussed by the
      TDDFT calculations.

PMID- 16805506
TI  - Definition of a nucleophilicity scale.
AB  - This work deals with exploring some empirical scales of nucleophilicity. We have
      started evaluating the experimental indices of nucleophilicity proposed by Legon
      and Millen on the basis of the measure of the force constants derived from
      vibrational frequencies using a probe dipole H-X (X = F,CN). The correlation
      among some theoretical parameters with this experimental scale has been
      evaluated. The theoretical parameters have been chosen as the minimum of the
      electrostatic potential V(min), the binding energy (BE) between the nucleophile
      and the H-X dipole, and the electrostatic potential measured at the position of
      the hydrogen atom V(H) when the complex nucleophile and dipole H-X is in the
      equilibrium geometry. All of them present good correlations with the experimental
      nucleophilicity scale. In addition, the BEs of the nucleophiles with two other
      Lewis acids (one hard, BF(3), and the other soft, BH(3)) have been evaluated. The
      results suggest that the Legon and Millen nucleophilicity scale and the
      electrostatic potential derived scales can describe in good approximation the
      reactivity order of the nucleophiles only when the interactions with a probe
      electrophile is of the hard-hard type. For a covalent interaction that is orbital
      controlled, a new nucleophilicity index using information of the frontier
      orbitals of both, the nucleophile and the electrophile has been proposed.

PMID- 16805507
TI  - Theoretical study of the isomerization mechanism of azobenzene and disubstituted
      azobenzene derivatives.
AB  - A series of azobenzenes was studied using ab initio methods to determine the
      substituent effects on the isomerization pathways. Energy barriers were
      determined from three-dimensional potential energy surfaces of the ground and
      electronically excited states. In the ground state (S(0)), the inversion pathway
      was found to be preferred. Our results show that electron donating substituents
      increase the isomerization barrier along the inversion pathway, whereas electron
      withdrawing substituents decrease it. The inversion pathway of the first excited
      state (S(1)) showed trans --> cis barriers with no curve crossing between S(0)
      and S(1). In contrast, a conical intersection was found between the ground and
      first excited states along the rotation pathway for each of the azobenzenes
      studied. No barriers were found in this pathway, and we therefore postulate that
      after n --> pi (S(1) <-- S(0)) excitation, the rotation mechanism dominates. Upon
      pi --> pi (S(2) <-- S(0)) excitation, there may be sufficient energy to open an
      additional pathway (concerted-inversion) as proposed by Diau. Our potential
      energy surface explains the experimentally observed difference in trans-to-cis
      quantum yields between S(1) and S(2) excitations. The concerted inversion channel
      is not available to the remaining azobenzenes, and so they must employ the
      rotation pathway for both n --> pi and pi --> pi excitations.

PMID- 16805508
TI  - Semiclassical treatment of thermally activated electron transfer in the
      intermediate to strong electronic coupling regime under the fast dielectric
      relaxation.
AB  - The generalized nonadiabatic transition-state theory (NA-TST) (Zhao, Y.; et al.
      J. Chem. Phys. 2004, 121, 8854) is used to study electron transfer with use of
      the Zhu-Nakamura (ZN) formulas of nonadiabatic transition in the case of fast
      dielectric relaxation. The rate constant is expressed as a product of the well
      known Marcus formula and a coefficient which represents the correction due to the
      strong electronic coupling. In the case of general multidimensional systems, the
      Monte Carlo approach is utilized to evaluate the rate by taking into account the
      multidimensionality of the crossing seam surface. Numerical demonstration is made
      by using a model system of a collection of harmonic oscillators in the Marcus
      normal region. The results are naturally coincident with the perturbation theory
      in the weak electronic coupling limit; while in the intermediate to strong
      electronic coupling regime where the perturbation theory breaks down the present
      results are in good agreement with those from the quantum mechanical flux-flux
      correlation function within the model of effective one-dimensional mode.

PMID- 16805509
TI  - Evolution of structure in CH5 + and its deuterated analogues.
AB  - Diffusion Monte Carlo simulations are used to investigate the effects of
      deuteration on the fluxionality of CH(5)(+) or CD(5)(+), using an ab initio
      potential surface, developed by Jin, Braams, and Bowman [J. Phys. Chem. 2006,
      110, 1569]. We find that partial deuteration quenches the fluxional behavior. The
      spectral consequences are also investigated. We find that, while CH(5)(+) and
      CD(5)(+) are nearly spherical tops, partial deuteration breaks the rotational
      symmetry and the mixed isotopologues are generally better characterized as
      symmetric tops. In addition, we investigate the effects of deuteration on the low
      resolution vibrational spectrum and anticipate that signatures of this
      delocalization will be observable in the vibrational spectrum.

PMID- 16805510
TI  - Effect of an S1/S0 conical intersection on the chemistry of nitramide in its
      ground state. A comparative CASPT2 study of the nitro-nitrite isomerization
      reactions in nitramide and nitromethane.
AB  - The potential energy surfaces for the dissociation of nitramide (NH(2)NO(2) -->
      NH(2) + NO(2)) and nitromethane (CH(3)NO(2) --> CH(3) + NO(2)) and the nitro
      nitrite rearrangement of these nitrocompounds (RNO(2) --> RONO) as well as the
      dissociations of the nitrite isomers (RONO --> RO + NO) have been studied with
      the second-order multiconfigurational perturbation theory (CASPT2) by computation
      of numerical energy gradients for stationary points. It is found that
      multiconfigurational methods [CASPT2 and complete active space SCF (CAS-SCF)]
      predict that the isomerization of nitramide to NH(2)ONO occurs in a two-step
      mechanism: (i) NH(2)NO(2) --> NH(2) + NO(2) and (ii) NH(2) + NO(2) --> NH(2)ONO,
      the second step involving surmounting an activation barrier. Contrastingly,
      Hartree-Fock based approaches give isomerization as a one-step reaction.
      Additionally, both mono- and multiconfigurational methods predict that nitro
      nitrite rearrangement of CH(3)NO(2) is a one-step process. The difference in the
      reaction mechanisms of these two isoelectronic molecules arises from the presence
      of an S(1)/S(0) conical intersection in nitramide which is absent in
      nitromethane.

PMID- 16805511
TI  - Computational study of the deamination reaction of cytosine with H2O and OH-.
AB  - The mechanism for the deamination reaction of cytosine with H(2)O and OH(-) to
      produce uracil was investigated using ab initio calculations. Optimized
      geometries of reactants, transition states, intermediates, and products were
      determined at RHF/6-31G(d), MP2/6-31G(d), and B3LYP/6-31G(d) levels and for
      anions at the B3LYP/6-31+G(d) level. Single-point energies were also determined
      at B3LYP/6-31+G(d), MP2/GTMP2Large, and G3MP2 levels of theory. Thermodynamic
      properties (DeltaE, DeltaH, and DeltaG), activation energies, enthalpies, and
      free energies of activation were calculated for each reaction pathway that was
      investigated. Intrinsic reaction coordinate analysis was performed to
      characterize the transition states on the potential energy surface. Two pathways
      for deamination with H(2)O were found, a five-step mechanism (pathway A) and a
      two-step mechanism (pathway B). The activation energy for the rate-determining
      steps, the formation of the tetrahedral intermediate for pathway A and the
      formation of the uracil tautomer for pathway B, are 221.3 and 260.3 kJ/mol,
      respectively, at the G3MP2 level of theory. The deamination reaction by either
      pathway is therefore unlikely because of the high barriers that are involved. Two
      pathways for deamination with OH(-) were also found, and both of them are five
      step mechanisms. Pathways C and D produce an initial tetrahedral intermediate by
      adding H(2)O to deprotonated cytosine which then undergoes three conformational
      changes. The final intermediate dissociates to product via a 1-3 proton shift.
      Deamination with OH(-), through pathway C, resulted in the lowest activation
      energy, 148.0 kJ/mol, at the G3MP2 level of theory.

PMID- 16805512
TI  - Pyrrolidine-thiourea as a bifunctional organocatalyst: highly enantioselective
      Michael addition of cyclohexanone to nitroolefins.
AB  - [reaction: see text] Asymmetric Michael additions of cyclohexanone to both aryl
      and alkyl nitroolefins in the presence of 20 mol % of organocatalyst 2b and 10
      mol % of n-butyric acid afford adducts 5 with high diastereoselectivities and
      enantioselectivities.

PMID- 16805513
TI  - Double lawton SN2'addition to epoxyvinyl sulfones: selective construction of the
      stereotetrads of aplyronine A.
AB  - [reaction: see text] Enantiopure epoxyvinyl sulfones function as templates for
      the diastereoselective construction of the three stereotetrads of aplyronine A.
      Lawton S(N)2' addition of 3,5-dimethylpyrazole followed by its displacement in an
      alcohol-directed Lawton S(N)2' reaction establishes the required product
      stereochemistry with high selectivity.

PMID- 16805514
TI  - Diastereoselective, vinylogous mukaiyama aldol additions of silyloxy furans to
      cyclic ketones: annulation of butenolides and gamma-lactones.
AB  - [reaction: see text] Vinylogous Mukaiyama aldol reactions employing
      silyloxyfurans and substituted cyclic ketones are described. These annulations
      proceed with moderate to good diastereoselectivity. The potential application of
      this process to the synthesis of butenolide and gamma-lactone containing natural
      products was demonstrated by further transformations of the addition products.

PMID- 16805515
TI  - Heterodimerization studies of calix[4]arene derivatives in polar solvents.
AB  - [reaction: see text] Several calix[4]arene derivatives propylated on the lower
      rim and substituted on the upper rim with amino or carboxyl groups have been
      synthesized. Examples include calixarenes substituted with alanino (C- and N
      linked), amino, carboxy, carboxyphenyl, and amidino groups. The self-assembly of
      these derivatized calixarenes into heterodimers has been studied by NMR in DMSO
      d(6) or CD(3)OD with 5% aqueous phosphate buffer.

PMID- 16805516
TI  - Intramolecular asymmetric Heck reactions: evidence for dynamic kinetic resolution
      effects.
AB  - [reaction: see text] Enantioselectivity of the cyclization of 1 varies at
      different stages in the reaction. X-ray crystallography has shown that 1 exists
      as enantiomerically pure (M) and (P) chiral helical structures defined by the
      relative orientations of the arene, amide, and alkene. The relative rates of
      interconversion of the rotamers of 1 have been established, leading to
      mechanistic proposals to account for the variation of ee based on kinetic
      resolution effects.

PMID- 16805517
TI  - Unprecedented selectivity in the formation of large-ring oligoimines from
      conformationally bistable chiral diamines.
AB  - [reaction: see text] Stereoselective formation of large macrocycles in "click
      type" reactions is a current challenge. Chiral macrocycles of differing size and
      shape (e.g., rectanglimine or loopimine) were selectively obtained by
      cyclocondensation of terephthalaldehyde or isophthalaldehyde with
      conformationally bistable chiral diamines derived from trans-1,2
      diaminocyclohexane and aromatic dianhydrides. This opens new opportunities for
      the programmed synthesis of large-ring molecular assemblies.

PMID- 16805518
TI  - Experimental and computational probes of a self-assembled capsule.
AB  - [reaction: see text] This research was undertaken to explore the interior surface
      of a synthetic receptor 1.1 with arylpyridines as guests. The interior surface
      differentiates the guests through the recognition of their nitrogen atoms.
      Experimental and computational analyses revealed that there is a delicate balance
      of attractions and repulsions between the host and the lone pairs of guests.

PMID- 16805519
TI  - Ni-catalyzed Si-B addition to 1,3-dienes: disproportionation in lieu of
      silaboration.
AB  - [reaction: see text] Upon attempted silaboration of acyclic 1- and 1,4
      substituted 1,3-dienes, a new disproportionation reaction was discovered,
      yielding 1:1 mixtures of allylsilanes and dienylboranes. It was demonstrated
      that, as a key step in this new catalytic process, hydrogen is being transferred
      from one diene moiety to another.

PMID- 16805520
TI  - Synthesis and properties of trefoil-shaped tris(hexadehydrotribenzo[12]annulene)
      and tris(tetradehydrotribenzo[12]annulene).
AB  - [reaction: see text] Trefoil-shaped tris(hexadehydrotribenzo[12]annulene)
      possessing a substructure of the ultimate two-dimensional C(sp)-C(sp(2)) network,
      graphyne, and the related tris(tetradehydrotribenzo[12]annulene) were
      synthesized, and their ground- and excited-state properties were investigated.

PMID- 16805521
TI  - Recyclable self-assembly-supported catalyst for chelation-assisted hydroacylation
      of an olefin with a primary alcohol.
AB  - [reaction: see text] A novel recyclable catalyst for chelation-assisted
      hydroacylation of an olefin with a primary alcohol was developed by utilizing a
      hydrogen-bonding self-assembly motif consisting of a barbiturate bearing 2
      aminopyridin-4-yl group and 5-hexyl-2,4,6-triaminopyrimidine. This was further
      applied to a mixed catalyst system to recycle both organic and organometallic
      catalysts.

PMID- 16805522
TI  - Visualization of molecular recognition: a novel system based on charge-transfer
      complexes composed of 1,1'-bi-2-naphthol derivatives and p-benzoquinone.
AB  - [reaction: see text] Charge-transfer (CT) complexes composed of 1,1'-bi-2
      naphthol derivatives as an electron donor and p-benzoquinone as an acceptor serve
      as an excellent host system for visual molecular recognition. This is because
      they form inclusion crystals with guest aromatic compounds which display
      remarkably different colors depending on the structure of the component molecules
      and on the method of crystallization (i.e., solution crystallization or solid
      cogrinding of component crystals).

PMID- 16805523
TI  - Reduction of Cp2ZrCl2 with mischmetall: a new method for generating an efficient
      "Cp2Zr" equivalent.
AB  - [reaction: see text] A "Cp(2)Zr" equivalent is generated under mild conditions
      (THF, room temperature) by reducing Cp(2)ZrCl(2) with cheap and readily available
      mischmetall (an alloy of Ce, La, Nd, and Pr). Coupling reactions, including those
      of terminal alkynes, can efficiently be achieved by using this reagent.

PMID- 16805524
TI  - Reductive olefination of aldehydes via chromium Brook rearrangement.
AB  - [reaction: see text] The combination of CrCl(2) and silyl chlorides converts aryl
      and conjugated aldehydes into olefinic adducts in good to excellent yields. When
      constrained by structural features, the intermediate vic-diol can be isolated.
      Available data are consistent with a novel chromium Brook rearrangement.

PMID- 16805525
TI  - Physanolide A, a novel skeleton steroid, and other cytotoxic principles from
      Physalis angulata.
AB  - [reaction: see text] A novel withasteroid, physanolide A (1), with an
      unprecedented skeleton containing a seven-membered ring, and two new physalins,
      physalins U (2) and V (3), were isolated from Physalis angulata. The structures
      were elucidated from spectroscopic analysis, and plausible biosynthetic pathways
      were postulated. Physalins B (4), D (5), and F (6) showed strong cytotoxicity
      against multiple tumor cell lines, including KB, A431, HCT-8, PC-3, and ZR751,
      with EC(50) values less than 4 microg/mL.

PMID- 16805526
TI  - Unusual transannular cyclization products of sarcophytoxide, a 14-membered marine
      cembranoid: anomalous stereochemistry of epoxide-ketone rearrangement.
AB  - [reaction: see text] Treatment of sarcophytoxide with trimethylsilyl
      trifluoromethanesulfonate afforded an aromatic ketone as an unusual cyclization
      product. The modified Mosher's method and X-ray analysis performed on the
      aromatic ketone revealed that it is a 4:1 mixture of 8(R)- and 8(S)-enantiomers.
      It also suggested that the precursor ketone has 8(R)-configuration, which is
      contradictory to that expected from the ordinary epoxide-ketone rearrangement.

PMID- 16805527
TI  - Direct access to marine pyrrole-2-aminoimidazoles, oroidin, and derivatives, via
      new acyl-1,2-dihydropyridin intermediates.
AB  - [reaction: see text] A short synthesis of the C(11)N(5) oroidin derivatives is
      reported. The key step of the strategy is a one-pot oxidative bromine-mediated
      addition of protected guanidines to the N-acyl-1,2-dihydropyridines 9a-c. The new
      N-acyl-1,2-dihydropyridines were prepared directly from pyridine and pyrrole-2
      carbonyl chloride by reduction with borohydride reagent in one step.

PMID- 16805528
TI  - Synthesis of cyclopropene alpha-amino acids via enantioselective
      desymmetrization.
AB  - [reaction: see text] The preparation of cyclopropene alpha-amino acids via the
      enantioselective desymmetrization of cyclopropene bis-carboxylic acid derivatives
      is described. The amino acids are stable to harsh reaction conditions, and a
      derivative has been incorporated into a tripeptide using conventional methods for
      peptide synthesis.

PMID- 16805529
TI  - Applications of asymmetric hydrosilylations mediated by catalytic (DTBM
      SEGPHOS)CuH.
AB  - [reaction: see text] Several aryl ketone precursors useful in the synthesis of
      known physiologically active compounds have been reduced to the corresponding
      nonracemic alcohols. The previously reported combination of a catalytic quantity
      of (R)-(-)-DTBM-SEGPHOS-ligated CuH and stoichiometric PMHS is shown to be very
      effective in these asymmetric hydrosilylations.

PMID- 16805531
TI  - Copper(I)-Fesulphos Lewis Acid catalysts for enantioselective Mannich-type
      reaction of N-sulfonyl imines.
AB  - [reaction: see text] Copper(I) complexes of Fesulphos ligands are efficient
      chiral Lewis acid catalysts in the Mannich-type addition of silyl enol ethers of
      ketones, esters, and thioesters to N-(2-thienyl)sulfonyl aldimines. The
      corresponding optically active beta-amino carbonyl derivatives were obtained in
      good yields (58-91%) and with moderate to good enantioselectivity (61-93% ee).
      Removal of the N-activating group was achieved under mild conditions by simple
      treatment of the products with Mg in methanol.

PMID- 16805530
TI  - Synthetic studies on taxol: highly stereoselective construction of the taxol C
      ring via SN2' reduction of an allylic phosphonium salt.
AB  - [reaction: see text] The highly stereoselective construction of the C3
      stereogenic center of the taxol C-ring is described. The trans isomer at the C3
      C8 position of the taxol C-ring, which is required for the total synthesis, as
      well as its diastereomeric cis isomer were successfully synthesized with highly
      diastereoselective S(N)2' reduction of the allylic phosphonium salts.

PMID- 16805532
TI  - Dendrimer analogues of linear molecules to evaluate energy and charge-transfer
      properties.
AB  - [reaction: see text] We have designed and synthesized difunctionalized dendrimers
      containing two donors in the periphery and an acceptor at the core to serve as
      scaffolds for comparison with linear analogues to investigate the advantage of
      dendritic scaffolds for energy and charge transfer. Comparison of these
      dendrimers with the fully decorated dendrimers provides information on the
      advantage of chromophore density in energy/charge transfer from periphery to the
      core.

PMID- 16805533
TI  - Stereoselective synthesis of pyridinones: application to the synthesis of (-)
      barrenazines.
AB  - [reaction: see text] The stereoselective synthesis of pyridinones was
      accomplished by the nucleophilic addition of Grignard reagents to a chiral
      pyridinium salt derived from 4-methoxypyridine. This methodology was applied to
      an expedient synthesis of (-)-barrenazine A and B. After N-functionalization and
      1,4-reduction of the pyridinone system, the corresponding alpha-amino
      piperidinones readily undergo dimerization to give the
      hexahydrodipyridinopyrazine skeleton of the barrenazine alkaloids.

PMID- 16805534
TI  - Origins of selectivity in pericyclic reaction cascades for the synthesis of
      gambogin and lateriflorone.
AB  - [reaction: see text] Quantum mechanical calculations demonstrate that the second
      step of a Claisen-Diels-Alder reaction cascade controls regioselectivity that
      gives advanced intermediates for the synthesis of gambogin and 1-O
      methyllateriflorone.

PMID- 16805535
TI  - Total synthesis of cryptophycin analogues via a scaffold approach.
AB  - [reaction: see text] Allylation of in situ generated beta,gamma-unsaturated
      aldehydes affords rapid access to vinyl halide analogues of fragment A of the
      cryptophycins. Three scaffolds are prepared in gram quantities by a ring-closing
      metathesis approach. Derivatization via a variety of cross-coupling protocols is
      possible, which affords novel analogues of these potent antimitotic agents.

PMID- 16805536
TI  - Synthesis of the spirastrellolide A trioxadispiroketal.
AB  - [reaction: see text] The core trioxadispiroketal system representing C26-C40 of
      spirastrellolide A was assembled using a sequenced double-intramolecular hetero
      Michael addition process.

PMID- 16805537
TI  - Evidence for the formation of the (Ph3P)2Pt complex of 3,7
      dimethyltricyclo[3.3.0.03,7]oct-1(5)-ene, the most highly pyramidalized alkene in
      a homologous series. Isolation and X-ray structure of the product of the ethanol
      addition to the complex.
AB  - [reaction: see text] Attempts to isolate the (Ph(3)P)(2)Pt complex of the highly
      pyramidalized olefin 3,7-dimethyltricyclo[3.3.0.0(3,7)]oct-1(5)-ene 2 by
      generation of 2 in the presence of (Ph(3)P)(2)PtC(2)H(4), followed by
      crystallization of the complex (2-Pt) from THF-ethanol, resulted in the isolation
      of the adduct of 2-Pt with ethanol (5). Calculations confirm that addition of
      alcohol across the C1-C5 bond is more favorable in 2-Pt than in the corresponding
      (Ph(3)P)(2)Pt complexes of less pyramidalized olefins, despite the stronger Pt-C
      bonds in 2-Pt.

PMID- 16805538
TI  - Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid
      mediated by gamma-cyclodextrins with a flexible or rigid cap.
AB  - [reaction: see text] A series of modified gamma-cyclodextrins (CDs) with a
      flexible or rigid cap, synthesized and used as chiral supramolecular hosts for
      mediating the enantiodifferentiating photocyclodimerization of 2
      anthracenecarboxylic acid, significantly improved the chemical and optical yields
      of chiral head-to-head cyclodimer 3, while the gamma-CD with a rigid cap
      dramatically inverted the stereochemical outcomes and further improved the
      enantioselectivities of both head-to-tail and head-to-head dimers 2 and 3.

PMID- 16805539
TI  - alpha-CD/crown-appended diazophenol for selective sensing of amines.
AB  - [reaction: see text] Azophenol dyes having the permethylated cyclodextrin and/or
      crown moieties have been synthesized. Compound 1 provides critical information on
      discriminating 1-3 degrees amines with unique color changes. Addition of 1
      degrees and 2 degrees amines to 1 shifts the absorbance maximum of 1 from 380 to
      approximately 580 and approximately 530 nm, respectively, but no change is
      observed with 3 degrees amines. The high selectivity of 1 is mainly due to H
      bonding between the ammonium H atoms of the amine and oxygen atoms of the crown
      6.

PMID- 16805540
TI  - Highly enantioselective CH oxidation of vic-Diols with Shi's oxazolidinone
      dioxiranes.
AB  - [reaction: see text] Through an analogical study of the transition states of CH
      oxidation and asymmetric epoxidation of terminal alkenes, the first dioxirane
      mediated catalytic highly enantioselective CH oxidation method was realized with
      Shi's oxazolidinone ketone derivatives. Very good enantioselectivity (up to 92%
      ee) may be obtained for both asymmetrization of meso vic-diols and kinetic
      resolution of racemic vic-diols.

PMID- 16805541
TI  - Novel and selective palladium-catalyzed annulations of 2-alkynylphenols to form 2
      substituted 3-halobenzo[b]furans.
AB  - [reaction: see text] A novel and selective palladium-catalyzed annulation of 2
      alkynylphenols method for the synthesis of 2-substituted 3-halobenzo[b]furans is
      presented. In the presence of PdX(2), CuX(2), and HEt(3)NX, 2-substituted 3
      halobenzo[b]furans were selectively obtained as the major products. The mechanism
      of the reaction was also discussed.

PMID- 16805542
TI  - Radicamines A and B: synthesis and revision of the absolute configuration.
AB  - [reaction: see text] Starting from D-xylose, enantioselective syntheses of 1 and
      2, the proposed structures for radicamines A and B, were accomplished. Both (1)H
      and (13)C NMR spectra of 1 and 2 were identical with those of the natural
      products, but the optical rotation measurements identified that 1 and 2 were
      actually the enantiomers of the natural radicamines A and B, respectively.

PMID- 16805543
TI  - Catalytic enantioselective borohydride reduction of ortho-fluorinated
      benzophenones.
AB  - [reaction: see text] In the presence of the optically active
      ketoiminatocobalt(II) complexes, the enantioselective borohydride reduction of
      benzophenones was successfully completed. The fluorine atom on the ortho position
      of the benzophenone and aryl ketones proved effective for obtaining high
      enantioselectivities. The combined use of modified lithium borohydride afforded
      the corresponding benzhydrols and arylcarbinols in high yield and high
      enantioselectivity (88-96% ee).

PMID- 16805544
TI  - High chelation control of three contiguous stereogenic centers in the Reformatsky
      reactions of indium enolates with alpha-hydroxy ketones: unexpected
      stereochemistry of lactone formation.
AB  - [reaction: see text] A boat-type of chelated bicyclic transition state involving
      highly diastereoselective construction of three contiguous stereogenic centers in
      the Reformatsky reaction of indium enolates with alpha-alkoxy/hydroxy ketones is
      proposed. alpha-Hydroxy ketones with indium enolates furnished highly
      diastereoselective lactones, while alpha-alkoxy ketones gave acyclic esters in
      moderate selectivities. X-ray structure analyses of key products unequivocally
      revealed the unexpected stereochemistry of products and the reaction pathway.

PMID- 16805546
TI  - Novel Rh catalysis in cross-coupling between alkyl halides and arylzinc compounds
      possessing ortho-COX (X = OR, NMe2, or Ph) groups.
AB  - [reaction: see text] Rh-dppf was found to be an efficient catalyst for the cross
      coupling between primary alkyl halides bearing beta-hydrogens and arylzinc
      compounds possessing carbonyl groups such as ester, amide, or ketone at the ortho
      position. Various functional groups such as ester, nitrile, or acyloxylate
      moieties on the halides were tolerated under the catalysis conditions. Arylzinc
      compounds free of ortho-carbonyl groups reacted well with ethyl 3-iodopropanoate,
      suggesting that the essential intramolecular interaction between carbonyl groups
      and Rh promotes the reductive elimination.

PMID- 16805545
TI  - Efficient synthesis of fused bicyclic glutarimides. Its application to (+/-)
      alloyohimbane and louisianin D.
AB  - [reaction: see text] The reaction of alpha-sulfonyl acetamide 1 with various
      cyclic unsaturated esters 2 to fused bicyclic glutarimides is reported. Syntheses
      of (+/-)-alloyohimbane (4) and louisianin D (5) have been accomplished.

PMID- 16805547
TI  - Skeletal rearrangements in the 2,3-diazanorbornene series. A fast access to
      highly functionalized cyclopentanes.
AB  - [reaction: see text] Acid-catalyzed nucleophilic substitution of bicyclic
      hydrazine-epoxide involves nitrogen participation, leading to a skeletal
      rearrangement. This transformation enables the fast preparation of disubstituted
      bicyclic hydrazines in a regio- and stereoselective manner, leading to several
      polyfunctional diaminocyclopentanes after hydrogenolysis.

PMID- 16805548
TI  - l-Piperazine-2-carboxylic acid derived N-formamide as a highly enantioselective
      Lewis basic catalyst for hydrosilylation of N-aryl imines with an unprecedented
      substrate profile.
AB  - [reaction: see text] l-Piperazine-2-carboxylic acid derived N-formamides have
      been developed as highly enantioselective Lewis basic catalysts for the
      hydrosilylation of N-aryl imines with trichlorosilane. The arene sulfonyl group
      on N4 was found to be critical for the high enantioselectivity of the catalyst.
      High isolated yields (up to 99%) and enantioselectivities (up to 97%) were
      obtained for a broad range of substrates, including aromatic and aliphatic
      ketimines, particularly those with R(2) as relatively bulky alkyl groups.

PMID- 16805549
TI  - Unexpected ring expansion of an enantiopure imidazoline carbene ligand.
AB  - [reaction: see text] We report an unexpected ring expansion reaction of an
      enantiopure fenchone-derived imidazolinium salt during attempts to form copper
      complexes of the corresponding imidazoline carbene ligand. A N,N'-difenchyl
      piperazinone was formed in low yield together with the difenchyl-substituted five
      membered urea.

PMID- 16805550
TI  - Synthesis of 2-substituted 3-aroylindenes via palladium-catalyzed carbonylative
      cyclization of diethyl 2-(2-(1-alkynyl)phenyl)malonates with aryl halides.
AB  - [reaction: see text] The palladium-catalyzed reaction of readily accessible
      diethyl 2-(2-(1-alkynyl)phenyl)malonates with aryl halides under a balloon
      pressure of CO produced 2-substitued 3-aroylindenes in good yields. The reaction
      is believed to proceed via cyclization of the alkyne containing a proximate
      nucleophilic center promoted by an acylpalladium complex.

PMID- 16805551
TI  - C-15 thiazol-4-yl analogues of (E)-9,10-didehydroepothilone D: synthesis and
      cytotoxicity.
AB  - The syntheses and biological evaluation of six epothilone D analogues are
      reported. These side-chain variants of the (E)-9,10-didehydroepothilone scaffold
      contain C-15 thiazole appendages that are derived from bromomethyl ketone
      intermediates. Although each of these analogues is less cytotoxic than the parent
      (E)-9,10-didehydroepothilone D, three maintain IC(50) values in the double-digit
      nanomolar range against both susceptible and resistant cell lines.

PMID- 16805552
TI  - Asymmetric gamma-deprotonation and homoaldol reaction of 1,3-dien-2-yl
      carbamates: stereo- and regiochemistry.
AB  - [reaction: see text] Lithium compounds 7 are configurationally stable
      intermediates obtained by deprotonation of 1,3-dien-2-yl carbamates 6 with n
      butyllithium/(-)-sparteine with a high degree of enantiotopic differentiation at
      the gamma-position. They react with electrophiles regioselectively giving highly
      enantioenriched products. Starting with different isomers or changing the double
      bond geometries in 6 leads to either of the enantiomers.

PMID- 16805553
TI  - Mechanism of NO transfer from NO-donors (SNAP and G-MNBS) to ferrous
      tetraphenylporphyrin in CH3OH.
AB  - [reaction: see text] The mechanism of NO transfer from NO-donors (SNAP and G
      MNBS) to ferrous tetraphenylporphyrin (TPPFe(II)) in CH(3)OH is discovered for
      the first time by using a laser flash technique. The results show that the NO
      transfer is completed by NO(+) transfer followed by electron transfer rather than
      direct NO transfer in one step.

PMID- 16805554
TI  - Stereodivergent syntheses of conduramines and aminocyclitols.
AB  - [reaction: see text] The diastereomers of 6-amino-cyclohex-3-ene-1,2-diols 1 (4
      deoxy-3-conduramines), key building blocks for the syntheses of a large range of
      natural products, have been enantioselectively prepared. Diastereoselective
      dihydroxylation of the compounds provided a new family of aminocyclitols 2
      (deoxyinosamines). The key reactions of our syntheses are Sharpless catalytic
      asymmetric epoxidation, diastereoselective addition of vinylmetal reagents to the
      aldehydes, and ring-closing metathesis (RCM).

PMID- 16805555
TI  - Transformation of an irregularly bridged epidithiodiketopiperazine to
      trichodermamide A.
AB  - [reaction: see text] An unusually bridged epidithiodiketopiperazine,
      pretrichodermamide A (3), was isolated from the fungus Trichoderma sp. BCC 5926.
      During the extensive effort to crystallize 3 for X-ray crystallographic analysis,
      conversion of this compound to trichodermamide A with coproduction of S(8)
      occurred.

PMID- 16805557
TI  - A highly efficient chemoenzymatic approach toward glycoprotein synthesis.
AB  - [reaction: see text] A highly efficient endoglycosidase-catalyzed synthesis of
      homogeneous glycoproteins is described. By using ribonuclease B as a model
      system, it was demonstrated that Endo-A could efficiently attach a preassembled
      oligosaccharide to a GlcNAc-containing protein in a regio- and stereospecific
      manner, when the corresponding sugar oxazoline was used as the donor substrate.
      The method allows the synthesis of both natural and tailor-made N-linked
      glycoproteins in excellent yield.

PMID- 16805556
TI  - A recyclable fluorous (S)-pyrrolidine sulfonamide promoted direct, highly
      enantioselective Michael addition of ketones and aldehydes to nitroolefins in
      water.
AB  - [reaction: see text] A recycle and reusable fluorous (S)-pyrrolidine sulfonamide
      organocatalyst has been developed for promoting highly enantio- and
      diastereoselective Michael addition reactions of ketones and aldehydes with
      nitroolefins in water. The organocatalyst is conveniently recovered from the
      reaction mixtures by fluorous solid-phase extraction and can be subsequently
      reused (up to six cycles) without a significant loss of catalytic activity and
      stereoselectivity.

PMID- 16805558
TI  - Four novel gelsenicine-related oxindole alkaloids from the leaves of Gelsemium
      elegans benth.
AB  - [reaction: see text] New types of four gelsenicine-related oxindole alkaloids
      were isolated from the leaves of Gelsemium elegans Benth. Gelsedilam (1) and 14
      acetoxygelsedilam (2) are the first examples of 18,19-nor-type monoterpenoid
      indole alkaloids. Gelsefuranidine (3) and gelseiridone (4) have, respectively, an
      additional furan residue or an iridoid unit on the gelsenicine-related
      monoterpenoid indole alkaloid.

PMID- 16805559
TI  - A [3 + 3] annelation approach to tetrahydropyridines.
AB  - [reaction: see text] A stepwise [3+3] annelation sequence to tetrahydropyridines
      via addition of the Buchi Grignard to aziridines has been developed. These
      intermediates can be further functionalized with good regio- and stereocontrol
      and this methodology has been employed in the stereoselective formal synthesis of
      (-)-dihydropinidine.

PMID- 16805560
TI  - Cobalt-mediated cross-coupling reactions of primary and secondary alkyl halides
      with 1-(trimethylsilyl)ethenyl- and 2-trimethylsilylethynylmagnesium reagents.
AB  - [reaction: see text] This paper describes cobalt-mediated cross-coupling
      reactions of alkyl halides with 1-(trimethylsilyl)ethenylmagnesium bromide and 2
      (trimethylsilyl)ethynylmagnesium bromide, respectively. The cobalt system allows
      for employing secondary as well as primary alkyl halides as the substrates. The
      reactions offer facile formations of alkyl-alkenyl and alkyl-alkynyl bonds. The
      reaction mechanism would include single-electron transfer from a cobalt complex
      to alkyl halide to generate the corresponding alkyl radical. The cobalt system
      thus enables sequential radical cyclization/alkenylation and
      cyclization/alkynylation reactions of 6-halo-1-hexene derivatives.

PMID- 16805561
TI  - TADDOL-derived phosphites and phosphoramidites for efficient rhodium-catalyzed
      asymmetric hydroboration.
AB  - [reaction: see text] Two simple TADDOL-derived monodentate ligands, the (1R,2S)-2
      phenylcyclohexanol-derived phosphite and the N,N-(phenylbenzyl)phosphoramidite,
      give comparably high levels of enantioselectivity (90-96% ee) in the rhodium
      catalyzed hydroborations of substituted styrenes bearing either electron-donating
      or electron-withdrawing substituents. Rhodium(I) chloride and tetrafluoroborate
      catalyst precursors give comparable results. Pinacolborane is superior to
      catecholborane in these reactions.

PMID- 16805562
TI  - Cross metathesis as a general strategy for the synthesis of prostacyclin and
      prostaglandin analogues.
AB  - [reaction: see text] A cross metathesis (CM) approach has been successfully
      applied to introduce fully functionalized omega-side chain appendages of various
      prostacyclin and prostaglandin analogues, resulting in high (E)-selectivities for
      the C13-C14 double bond and leading to the total syntheses of isocarbacyclin, 15R
      TIC, carbacyclin, and PGF(2)(alpha) and the formal syntheses of 15-deoxy-TIC and
      PGJ(2).

PMID- 16805563
TI  - Transition states of the retro-ene reactions of allylic diazenes.
AB  - [reaction: see text] Density functional theory studies of intramolecular retro
      ene reactions of allyldiazenes show that the reaction is a concerted process
      involving a six-center cyclic transition state. The activation barriers for
      deazetization for X = H, Me, F, Cl, and Br (3a-e) are 2.4, 40.2, 22.3, 9.3, and
      8.8 kcal/mol, respectively.

PMID- 16805564
TI  - Visualization method to predict the nucleophilic asymmetric induction of
      prochiral electrophiles.
AB  - [reaction: see text] This work focuses on the development of a simple technique
      to accurately predict and visualize the diastereoselectivity of ketone, aldehyde,
      and allyl chloride reductions by mapping electrostatic potential onto the
      frontier molecular orbital involved in the reduction. A distinct difference of
      electrostatic potential on the faces of the carbonyl can be used to predict the
      face of nucleophilic attack with a high level of accuracy.

PMID- 16805565
TI  - Allenyl azide cycloaddition chemistry. Synthesis of annelated indoles from 2
      (allenyl)phenyl azide substrates.
AB  - [reaction: see text] Thermolysis of 2-(allenyl)phenyl azides leads to a cascade
      cyclization sequence furnishing both C(2)-C(3) and N-C(2) cyclopentannelated
      indoles.

PMID- 16805566
TI  - Studies of new indole alkaloid coupling methods for the synthesis of
      haplophytine.
AB  - [reaction: see text] The two novel bisindole alkaloid structures shown can be
      synthesized in a few steps from the canthiphytine derivative 9.

PMID- 16805568
TI  - Reversible interconversion between a supramolecular polymer and a discrete
      octameric species from a guanosine derivative by dynamic cation binding and
      release.
AB  - [reaction: see text] The tunable interconversion between two highly ordered
      supramolecular motifs (G-quartet K(+)-templated column and G-ribbon) of a
      lipophilic guanosine derivative fueled by cation complexation and release in a
      cryptand [2.2.2] containing guanosine solution is reported. The process is
      controlled by the sequential addition of acid and base.

PMID- 16805567
TI  - New entry into beta-lactams via reaction of dimethoxycarbene with isocyanates.
AB  - [reaction: see text] Highly substituted beta-lactams have been isolated as the
      major product of the reaction of dimethoxycarbene with selected isocyanates. This
      reaction offers the potential for rapid access into a variety of highly
      functionalized species.

PMID- 16805569
TI  - Use of alpha-chlorinated N-(tert-butanesulfinyl)imines in the synthesis of chiral
      aziridines.
AB  - [reaction: see text] Reaction of chiral alpha-chloro tert-butanesulfinyl
      aldimines with Grignard reagents efficiently afforded beta-chloro N-sulfinamides
      in high diastereomeric excess. The latter compounds were cyclized toward the
      corresponding chiral aziridines in a high-yielding one-pot reaction or after
      separate treatment with base. The diastereoselectivity obtained in the newly
      synthesized beta-chloro sulfinamides is explained via the coordinating ability of
      the alpha-chloro atom with magnesium resulting in the opposite stereochemical
      outcome as generally observed for nonfunctionalized N-sulfinyl imines.

PMID- 16805570
TI  - Novel annulation reactions of aryl methyl ketenes with zwitterions derived from
      dimethyl acetylenedicarboxylate and N-alkylimidazoles.
AB  - [reaction: see text] A novel three-component annulation reaction involving N
      alkylimidazoles, dimethyl acetylenedicarboxylate, and in situ generated aryl
      methyl ketenes leading to the synthesis of 6-vinyl-1,3a-diazapentalene
      derivatives is reported.

PMID- 16805571
TI  - Novel metal-free hydrogenation of the carbon-carbon double bond in azulenoid
      enones by use of cycloheptatriene and protic acid.
AB  - [reaction: see text] An efficient method for the hydrogenation of the carbon
      carbon double bond in azulenoid and aromatic fused azulenoid enones without the
      use of hydrogen and a metal catalyst is reported. Treatment of a variety of
      azulenoid enones with cycloheptatriene and a protic acid in acetonitrile gave the
      corresponding beta-azulenyl ketone derivatives in excellent to moderate yield. In
      this reaction, cycloheptatriene acts as a hydride donor.

PMID- 16805572
TI  - Mild iodine-magnesium exchange of iodoaromatics bearing a pyrimidine ring with
      isopropylmagnesium chloride.
AB  - [reaction: see text] Iodoaromatics bearing a reactive pyrimidine ring underwent a
      clean iodine-magnesium exchange with isopropylmagnesium chloride in the presence
      of bis[2-(N,N-dimethylamino)ethyl] ether to provide the corresponding Grignard
      reagents. The presence of bis[2-(N,N-dimethylamino)ethyl] ether prevented
      reduction of the pyrimidine ring and addition by isopropylmagnesium chloride. As
      a result, the newly formed reactive Grignard reagents were allowed to react with
      electrophiles in a highly selective manner to afford adducts in excellent yields.

PMID- 16805573
TI  - Chirality multiplication and efficient chirality transfer in exo- and endo
      radical cyclization reactions of 4-(4'-iodobutyl)quinolones.
AB  - [reaction: see text] Enantioselective radical cyclization reactions were
      performed in the presence of chiral complexing agent 1. The title compounds 3
      yielded, depending on the 3'-substitution (R = H, Me), the corresponding endo-
      (4) or exo-product (5). The highest enantioselectivities (99% and 94% ee) were
      achieved with 2.5 equiv of complexing agent. The cyclization product trans-4 was
      obtained in 55% ee in the presence of only 0.1 equiv of complexing agent.

PMID- 16805574
TI  - Mild manganese(III) acetate catalyzed allylic oxidation: application to simple
      and complex alkenes.
AB  - Manganese(III) acetate catalyzed allylic oxidation of alkenes to the
      corresponding enones was investigated, showing excellent regioselectivity and
      chemoselectivity (functional group compatibility). Delta(5)-Steroids were
      transformed into bioactive Delta(5)-en-7-ones under a nitrogen atmosphere,
      whereas simple alkenes were converted into the corresponding enones under an
      oxygen atmosphere in good yields.

PMID- 16805575
TI  - Metal-catalyzed chemoselective cycloisomerization of cis-2,4-dien-1-als to 3
      cyclopentenones and 4-alkylidene-3,4-dihydro-2H-pyrans.
AB  - [reaction: see text] PtCl(2) (5 mol %) catalyst effected cycloisomerization of
      cis-2,4-dien-1-al (1) to 3-cyclopentenone (3) efficiently in hot toluene. In the
      presence of p-TSA, this PtCl(2) catalysis gave 2-cyclopentenone (5) exclusively
      because of the secondary isomerization reaction. Although the 1-2 equilibrium
      state greatly favors aldehyde (1), PdCl(2)(PhCN)(2) (5 mol %) catalyzed
      cycloisomerization of aldehyde (1) to 4,6,7,8-tetrahydro-3H-isochromene (4)
      smoothly in hot toluene. A plausible mechanism is proposed on the basis of
      reaction observation and isotope-labeled experiment.

PMID- 16805578
TI  - Selective adsorption and alignment behaviors of double- and multiwalled carbon
      nanotubes on bare Au and SiO2 surfaces.
AB  - We present the study of selective adsorption and alignment behaviors of double-
      and multiwalled carbon nanotubes (dwCNTs and mwCNTs) on self-assembled monolayer
      (SAM) patterns, bare Au, and SiO2 surfaces. dwCNTs and mwCNTs exhibited stronger
      affinity to polar SAMs, bare Au, and SiO2 surfaces than to nonpolar SAM surfaces.
      Furthermore, we found the adsorption probability of smaller carbon nanotubes
      (CNTs) was higher than that of larger CNTs. As proof of concept, we successfully
      assembled and aligned dwCNTs and mwCNTs on Au and SiO2 substrates without relying
      on external forces and demonstrated wafer-scale fabrication of back-gate
      transistors based on dwCNTs with a high yield.

PMID- 16805577
TI  - Chiral close-packing of achiral star-shaped molecules on solid surfaces.
AB  - From the interplay of scanning tunneling microscopy and theoretical calculations,
      we study the chiral self-assembly of achiral HtB-HBC molecules upon adsorption on
      the Cu(110) surface. We find that chirality is expressed at two different levels:
      a +/-5 degrees rotation of the molecular axis with respect to the close-packed
      direction of the Cu(110) substrate and a chiral close-packed arrangement expected
      for star-shaped molecules in 2D. Out of the four possible chiral expressions,
      only two are found to exist due the effect of van der Waals (vdW) interactions
      forcing the molecules to simultaneously adjust to the atomic template of the
      substrate geometry and self-assemble in a close-packed geometry.

PMID- 16805579
TI  - Solvent effect on the singlet excited-state dynamics of 5-fluorouracil in
      acetonitrile as compared with water.
AB  - The excited-state dynamics of 5-fluorouracil in acetonitrile has been
      investigated by femtosecond fluorescence upconversion spectroscopy in combination
      with quantum chemistry TD-DFT calculations ((PCM/TD-PBE0). Experimentally, it was
      found that when going from water to acetonitrile solution the fluorescence decay
      of 5FU becomes much faster. The calculations show that this is related to the
      opening of an additional decay channel in acetonitrile solution since the dark
      n/pi* excited state becomes near degenerate with the bright pi/pi* state, forming
      a conical intersection close to the Franck-Condon region. In both solvents, a S1
      S0 conical intersection, governed by the out-of-plane motion of the fluorine
      atom, is active, allowing an ultrafast internal conversion to the ground state.

PMID- 16805580
TI  - Gd(III) polyaminocarboxylate chelate: realistic many-body molecular dynamics
      simulations for molecular imaging applications.
AB  - Realistic molecular dynamics simulations of polyaminocarboxylate complexes of
      gadolinium (III) ion in water are performed, providing coordination numbers and
      average residence times in quantitative agreement with available experimental
      data. A theoretical analysis, based on fitting a fluctuating charges model on ab
      initio data, also indicates that charge transfer between the ion and the ligand
      is significant.

PMID- 16805581
TI  - Enthalpy-entropy compensation in the effects of urea on hydrophobic interactions.
AB  - By comparison of neopentane pair potentials of mean force (PMFs) in room
      temperature water and 6.9 molar aqueous urea, it was recently shown that urea
      molecules affect the PMF minima in an unexpected way (Lee, M.-E.; van der Vegt,
      N. F. A. J. Am. Chem. Soc. 2006, 128, 4948). While the first PMF minimum in urea
      solution has an identical shape and depth to those of the corresponding minimum
      in water, the second minimum in urea solution is broader, deeper, and shifted out
      to a slightly larger distance. Here, we present a study of the enthalpic and
      entropic contributions to these PMFs. Its significance for understanding the
      driving forces responsible for thermodynamically favorable neopentane contact and
      solvent-separated distances in urea solution is discussed. We propose that the
      solute-solvent entropy and solute-solvent enthalpy changes should be analyzed for
      obtaining an unambiguous molecular-scale picture. In urea solution, enthalpy
      entropy compensation effects associated with structural solvent reorganization
      processes are large, causing changes of the system's enthalpy and entropy with
      hydrophobic pair separation to be very different from the solute-solvent enthalpy
      and entropy changes. The entropies are discussed in terms of the molecular-scale
      solvent reorganization processes.

PMID- 16805582
TI  - Magnetic field control of photoinduced silver nanoparticle formation.
AB  - The micellar photoreduction of benzophenone in the presence of Ag+ leads to very
      rapid and efficient formation of silver nanoperticles. External magnetic fields
      can be used to control the rate of formation and properties of silver
      nanoparticles generated by reaction of ketyl radicals formed in the
      photoreduction of benzophenone in surfactant micelles. The effect is attributed
      to Zeeman splitting of the triplet sublevels of the confined radical pair that
      causes a reduction in the rate of geminate processes and increases the
      availability of ketyl radicals (through escape processes) for metal ion
      reduction.

PMID- 16805583
TI  - Longitudinal polarizability of carbon nanotubes.
AB  - The longitudinal polarizabilities of carbon nanotubes are determined using first
      principles density functional theory. These results demonstrate that the
      polarizability per atom of a nanotube in the axial direction is primarily
      determined by the band gap. In fact, polarizability per atom versus inverse band
      gap yields a linear trend for all nanotubes and methods utilized in this study,
      creating a universal relationship for longitudinal polarizability. This can be
      explained by examining the terms in the sum over states equation used to
      determine polarizability and noting that the vast majority of the polarizability
      arises from a few elements near the band gap. This universal trend is then used
      with experimentally determined band gaps to predict the experimental
      polarizability of carbon nanotubes.

PMID- 16805584
TI  - Lasing mechanism of ZnO nanowires/nanobelts at room temperature.
AB  - ZnO has become the focus of photonics and optoelectronic research. We prepared
      pure Mn(II) doped ZnO nanowires with a controlled reduction reaction by carbon in
      an asymmetrical tube. Careful time-resolved photoluminescence experimental study
      indicates three types of lasing mechanisms: exciton-exciton interaction,
      bipolaronic exciton condensation, and plasma; these exist in different ZnO
      nanowires, which can be changed by doping Mn in ZnO nanowire. The transformation
      between varied mechanisms is discussed in detail with their spectral behaviors.
      These results are important in the design of future violet-blue luminescence and
      display devices.

PMID- 16805585
TI  - Sub-nanometer Au monolayer-protected clusters exhibiting molecule-like electronic
      behavior: quantitative high-angle annular dark-field scanning transmission
      electron microscopy and electrochemical characterization of clusters with precise
      atomic stoichiometry.
AB  - The synthesis and characterization of the clusters Au13[PPh3]4[S(CH2)11CH3]2Cl2
      (1) and Au13[PPh3]4[S(CH2)11CH3]4 (2) are described. These mixed-ligand, sub
      nanometer clusters, prepared via exchange of dodecanethiol onto phosphine-halide
      gold clusters, show enhanced stability relative to the parent. The
      characterization of these clusters features the precise determination of the
      number of gold atoms in the cluster cores using high-angle annular dark-field
      scanning transmission electron microscopy, allowing the assignment of 13 gold
      atoms (+/-3 atoms) to the composition of both cluster molecules. Electrochemical
      and optical measurements reveal discrete molecular orbital levels and apparent
      energy gaps of 1.6-1.7 eV for the two cluster molecules. The electrochemical
      measurements further indicate that the Au13[PPh3]4[S(CH2)11CH3]2Cl2 cluster
      undergoes an overall two-electron reduction. The electrochemical and
      spectroscopic properties of the two Au13 cluster molecules are compared with
      those of a secondary synthetic product, which proved to be larger Au thiolate
      derivatized monolayer-protected clusters with an average core of Au180. The
      latter shows behavior fully consistent with the adoption of metallic-like
      properties.

PMID- 16805586
TI  - Two-stage melting of Au-Pd nanoparticles.
AB  - Several series of molecular dynamics runs were performed to simulate the melting
      transition of bimetallic cuboctahedral nanoparticles of gold-palladium at
      different relative concentrations to study their structural properties before,
      in, and after the transition. The simulations were made in the canonical
      ensemble, each series covering a range of temperatures from 300 to 980 K, using
      the Rafii-Tabar version of the Sutton and Chen interatomic potential for metallic
      alloys. We found that the melting transition temperature has a strong dependence
      on the relative concentrations of the atomic species. We also found that,
      previous to the melting transition, the outer layer of the nanoparticle gets
      disordered in what can be thought as a premelting stage, where Au atoms near the
      surface migrate to the surface and remain there after the particle melts as a
      whole. The melting of the surface below Tm is consistent with studies of the
      interaction of a TEM electron beam with Au and Au-Pd nanoparticles.

PMID- 16805587
TI  - Optical transmittance of indium tin oxide nanoparticles prepared by laser-induced
      fragmentation in water.
AB  - Laser-induced fragmentation of indium tin oxide nanoparticles was performed in
      water by laser irradiation with various laser energies. Fragmentation of the
      nanoparticles proceeded with increased laser energy. The fragmented nanoparticles
      showed high transmittance in the visible region and lower transmittance in the
      ultraviolet and infrared regions. The optical band gap of the fragmented
      nanoparticles increased with decreasing average particle size. The increase of
      the band gap was possibly caused by the Burstein-Moss effect due to the
      increasing concentration of carriers generated by the surface defects of the
      oxygen vacancies on smaller nanoparticles.

PMID- 16805588
TI  - DNA detection method based on the two-dimensional aggregation and selective
      desorption of nanoparticle probes.
AB  - A label-free two-dimensional colorimetric DNA sensor is reported. This sensor is
      based on the 2D aggregation of oligonucleotide-modified gold nanoparticle probes
      induced by the molecular hybridization of single-stranded oligonucleotide probes
      and their complementary single-stranded DNA targets. To detect the aggregation,
      we have developed a new detection method based on the selective desorption of
      nonaggregated nanoparticles. We will show here that this detection method is
      highly specific and allows the quantification of the DNA targets.

PMID- 16805589
TI  - Quantum dot modified multiwall carbon nanotubes.
AB  - A novel strategy for the fabrication of multiwall carbon nanotube-nanocrystal
      heterostructures is shown. Different quantum dots (QDs) with narrow size
      distributions were covalently coupled to carbon nanotubes (CNTs) and silica
      coated CNTs in a simple, uniform, and controllable manner. The structural and
      optical properties of CNT/QD heterostructures are characterized by electron
      microscopy and photoluminescence spectroscopy. Complete quenching of the PL bands
      in both QD core and core/shell heterostructures was observed after adsorption to
      the CNTs, presumably through either carrier ionization or energy transfer. The
      deposition of a silica shell around the CNTs preserves the fluorescence
      properties by insulating the QD from the surface of the CNT.

PMID- 16805590
TI  - Equilibrium distribution of permeants in polyelectrolyte microcapsules filled
      with negatively charged polyelectrolyte: the influence of ionic strength and
      solvent polarity.
AB  - The effects of ionic strength and solvent polarity on the equilibrium
      distribution of fluorescein (FL) and FITC-dextran between the interior of
      polyelectrolyte multilayer microcapsules filled with negatively charged strong
      polyelectrolyte and the bulk solution were systematically investigated. A
      negatively charged strong polyelectrolyte, poly(styrene sulfonate) (PSS), used
      for CaCO3 core fabrication, was entrapped inside the capsules. Due to the
      semipermeability of the capsule wall, a Donnan equilibrium between the inner
      solution within the capsules and the bulk solution was created. The equilibrium
      distribution of the negatively charged permeants was investigated by means of
      confocal laser scanning microscopy as a function of ionic strength and solvent
      polarity. The equilibrium distribution of the negatively charged permeants could
      be tuned by increasing the bulk ionic strength to decrease the Donnan potential.
      Decreasing the solvent polarity also could enhance the permeation of FL, which
      induces a sudden increase of permeation when the ethanol volume fraction was
      higher than 0.7. This is mainly attributed to the precipitation of PSS. A
      theoretical model combining the Donnan equilibrium and Manning counterion
      condensation was employed to discuss the results.

PMID- 16805591
TI  - Poly(L-lactide) (PLLA)/multiwalled carbon nanotube (MWCNT) composite:
      characterization and biocompatibility evaluation.
AB  - Much effort has been directed at the fabrication of carbon nanotubes
      (CNTs)/polymer composites and the characterization of their physical properties.
      Among them, composites comprising CNTs and the biocompatible polymers are of
      special interest due to their potential for specific biomedical applications. we
      report the preparation of the MWCNT/poly(L-lactide) composite and the
      corresponding spectroscopic (Raman) and the microscopic (SEM, TEM)
      characterization. The electronic transport, thermal properties, and
      biocompatibility of this composite have also been investigated. The Raman
      spectroscopic analysis suggests the interaction between PLLA and MWCNT occurs
      mainly through the hydrophobic C-CH3 functional groups. The DC conductivity of
      the composite increases as the MWCNT loading is increased. Such behavior can be
      described by a percolation mechanism in which a percolation threshold at about 14
      wt % MWCNT loading is observed with the maximum end conductivity of 0.1 S x cm(
      1). The DSC study of the PLLA/MWCNT composite reveals that the MWCNTs in the
      composite have the effect of inducing crystallization and plasticizing the
      polymer matrix. The results from the cell culture test suggest that the presence
      of MWCNT in the composite inhibits the growth of the fibroblast cells.

PMID- 16805592
TI  - Enhanced electrorheological activity of mesoporous Cr-doped TiO2 from activated
      pore wall and high surface area.
AB  - To enhance electrorheological (ER) activity by improving interfacial
      polarization, we prepared a new mesoporous Cr-doped TiO2 ER material by a
      copolymer-templated sol-gel method. The material was characterized by
      differential scanning calorimeter and thermogravimetric (DSC-TG) analysis,
      Fourier transform infrared (FT-IR), X-ray powder diffraction (XRD), transmission
      electron microscopy (TEM), N2 adsorption, and X-ray photoelectron spectroscopy
      (XPS) techniques. The ER activity was studied by the rheological curve and yield
      stress under an electric field. The results showed that the mesoporous Cr-doped
      TiO2 ER material possessed a high surface area over 200 m2/g and a crystalline
      anatase pore wall doped by different valent Cr ions. The ER activity of
      mesoporous Cr-doped TiO2 was higher than that of nonporous Cr-doped TiO2. The
      yield stress and ER efficiency of the mesoporous Cr-doped TiO2 ER suspension was
      3 times as high as that of the nonporous Cr-doped TiO2 ER suspension, 7 times as
      high as that of the mesoporous undoped TiO2 ER suspension, and 20 times as high
      as that of the nonporous pure TiO2 ER suspension. Furthermore, the ER activity of
      mesoporous Cr-doped TiO2 showed a dependence on surface area, and the high
      porosity or surface area samples showed higher ER activity. The dielectric
      spectra analysis showed that the mesoporous Cr-doped TiO2 ER suspension possessed
      a significantly larger interfacial polarizability compared with the nonporous Cr
      doped TiO2 ER suspension, and the regular change of polarizability with surface
      area or porosity was in accordance with the change of ER activity with surface
      area or porosity. The improvement of dielectric properties or polarization could
      well explain the enhancement of the ER activity of mesoporous Cr-doped TiO2.

PMID- 16805593
TI  - Femtosecond time resolved fluorescence dynamics of a cationic water-soluble
      poly(fluorenevinylene-co-phenylenevinylene).
AB  - A recently synthesized cationic water-soluble poly(fluorenevinylene-co
      phenylenevinylene) was studied by means of steady state and femtosecond time
      resolved upconversion spectroscopy in aqueous and EtOH solutions. Steady state
      spectroscopic measurements showed that the polymer emits at the blue-green
      spectral region and that aggregates are formed in concentrated polymer solutions.
      The fluorescence dynamics of the polymer in concentrated solutions, studied at a
      range of emission wavelengths, exhibited a wavelength dependent and
      multiexponential decay, indicating the existence of various decay mechanisms.
      Specifically, a rapid decay at short emission wavelengths and a slow rise at long
      wavelengths were observed. Both features reveal an energy transfer process from
      isolated to aggregated chains. The contribution of the energy transfer process as
      well as of the isolated chains and the aggregates on the overall fluorescence
      decay of the polymer was determined. The dependence of the energy transfer rate
      and efficiency on polymer concentration was also examined.

PMID- 16805594
TI  - Hybrid materials for solid-state dye laser applications.
AB  - The quest for a solid-state tunable dye laser can be satisfied by sol-gel
      prepared organic-inorganic hybrids. A photostability study of porous silica
      Rhodamine 6G hybrids prepared via a sol-gel method is presented. The dye
      molecules can be incorporated into the silica matrix by forming weak or covalent
      bonds (hybrids of classes I and II, respectively). New class II samples and
      traditional class I materials prepared by the pre-doping method were synthesized.
      Samples were characterized by photoluminescence measurements to compare the
      emission properties and the photostability of the samples. The decay of the
      fluorescence signal as the cumulative excitation energy increases is reported and
      interpreted by hypothesizing that the dye molecules can be hosted in different
      surroundings within the porous glass matrix. The reported photoluminescence and
      photobleaching features indicate the class II samples as good candidates for
      solid-state dye lasers.

PMID- 16805595
TI  - Electrochemical modification of vertically aligned carbon nanotube arrays.
AB  - Electrochemical oxidation and reduction were utilized to modify vertically
      aligned carbon nanotube (CNT) arrays grown on a porous network of conductive
      carbon microfibers. Ultrafast and complete CNT opening and purification were
      achieved through electrochemical oxidation. Highly dispersed platinum
      nanoparticles were then uniformly and densely deposited as electrocatalysts onto
      the surface of these CNTs through electrochemical reduction. Using supercritical
      drying techniques, we demonstrate that the unidirectionally aligned and laterally
      spaced geometry of the CNT arrays can be fully retained after being subjected to
      each step of electrochemical modification. The open-tipped CNTs can also be
      electrochemically detached in full lengths from the supporting substrates and
      harvested if needed.

PMID- 16805596
TI  - Crystal lattice size and stability of type H clathrate hydrates with various
      large-molecule guest substances.
AB  - To gain a better understanding of the effects of guest molecules on the lattice
      and stability of type H hydrates, we performed powder X-ray diffraction (PXRD)
      measurements and semiempirical molecular orbital calculations. The unit cell
      parameters and cohesive energies of various type H hydrates that contain methane
      (CH4) were analyzed. PXRD measurements indicated that an increase in the large
      molecule guest volume caused the unit cell volume to increase. It was also
      indicated that a large-molecule guest substance caused the a-axis-direction of
      the unit cell to increase with little decrease in the c-axis direction.
      Calculations of cohesive energy by means of a semiempirical molecular orbital
      method indicated that the functional group and configuration of large-molecule
      guest substances affects the stability of type H hydrates. It was concluded that
      the icosahedron (5(12)6(8)) cages do not easily increase in length along the c
      axis direction when larger guest molecules are used to form the hydrate, but the
      5(12)6(8) cage and the layer of dodecahedron (5(12)) cages can easily increase in
      length along the a-axis direction due to interactions of the guest-host molecule.

PMID- 16805597
TI  - Solvothermal synthesis and photoluminescent properties of ZnS/cyclohexylamine:
      inorganic-organic hybrid semiconductor nanowires.
AB  - An inorganic-organic hybrid semiconductor, ZnS/CHA (CHA = cyclohexylamine)
      nanocomposites was successfully synthesized via a solvothermal method using CHA
      as solvent, which yielded uniform and ultralong nanowires with widths of 100-1000
      nm and lengths of 5-20 microm. Changing the reaction conditions could alter the
      morphology and optical properties of the nanocomposites. The periodic layer
      subnanometer structures were identified by high-resolution transmission electron
      microscopy (HR-TEM) images, with thickness of approximately 2 nm. The composites
      exhibited a very large blue-shift in their optical absorption edge as well as an
      exciton excitation band due to a strong quantum confinement effect caused by the
      internal subnanometer-scale structures. The pure hexagonal wurtzite ZnS nanowires
      were also obtained by extracting the ZnS/CHA nanocomposites with dimethyl
      formamide (DMF). In addition, the luminescent properties of exciton and defect
      related transitions in different samples of ZnS/CHA were discussed in detail.

PMID- 16805598
TI  - Formation of stable Ag-nanoparticle aggregates induced by dithiol cross-linking.
AB  - Aggregation of thiol-stabilized silver nanoparticles induced by 1,6-hexane
      dithiol was studied in situ by dynamic light scattering. The aggregates were
      observed to reach a finite size in the 100-200 nm range depending on the applied
      conditions. Growth kinetics were shown to be linked to the dynamics of the thiol
      exchange reaction. A model for the aggregation process was developed on the basis
      of a simple diffusion-kinetic approach assuming an elementary kinetic reaction at
      the surfaces and a spherical diffusion field surrounding the aggregates. The rate
      constant for the thiol exchange reaction was found to vary between 0.6 and 4.0 x
      10(-4) s(-1), and the activation energy was 46 +/- 10 kJ mol(-1).

PMID- 16805599
TI  - Salt and solvent effects on the kinetics and thermodynamics of the inclusion of
      the ruthenium complex [Ru(NH3)5(4,4'-bpy)]2+ in beta-cyclodextrin.
AB  - The influences of solvents (in water-cosolvent mixtures) and salts on the
      kinetics and thermodynamics of the inclusion of [Ru(NH3)5(4,4'-bpy)]2+ in beta
      cyclodextrin (beta-CD) have been studied. Solvent effects on the kinetics can be
      described as a consequence of the competition of the cosolvent for the beta-CD
      cavity. The salt effects on the kinetics depend on the ion pairing of the anions
      with the [Ru(NH3)5(4,4'-bpy)]2+ complex. On the other hand, the solvent effects
      on the equilibrium constant depend on the stabilization of the 4,4'-bipyridine
      ligand in the water-cosolvent mixture relative to water. Finally, salt effects on
      the equilibrium constant are interpreted as a consequence of ion pairing between
      the anion of the salt and the inclusion complex.

PMID- 16805600
TI  - Hydrogen storage properties of Li-Mg-N-H systems with different ratios of
      LiH/Mg(NH2)2.
AB  - In this work, the hydrogen desorption and structural properties of the Li-Mg-N-H
      systems with different LiH/Mg(NH2)2 ratios are systemically investigated. The
      results indicate that the system with the LiH/Mg(NH2)2 ratio of 6/3 transforms
      into Li2NH and MgNH, and then, the mixture forms an unknown phase by a solid
      solid reaction, which presumably is the ternary imide Li2Mg(NH)2; the system with
      the LiH/Mg(NH2)2 ratio of 8/3 transforms into 4Li2NH and Mg3N2 after releasing H2
      at T < 400 degrees C; the system with the LiH/Mg(NH2)2 ratio of 12/3 transforms
      into 4Li3N and Mg3N2 after releasing H2 at T > 400 degrees C, where the LiMgN
      phase is formed by the reaction between Li3N and Mg3N2. The characteristics of
      the phase transformations and the thermal gas desorption behaviors in these Li-Mg
      N-H systems could be reasonably explained by the ammonia mediated reaction model,
      irrespective of the difference in the LiH/Mg(NH2)2 ratios.

PMID- 16805601
TI  - Temperature- and pH-dependent morphology and FT-IR analysis of magnesium
      carbonate hydrates.
AB  - Various morphologies of magnesium carbonate hydrates have been synthesized by
      carefully adjusting the reaction temperature and pH value of the initial reaction
      solution in the precipitation process. At lower temperatures (from room
      temperature to 328 K) and lower pH values (variation with the reaction
      temperature), magnesium carbonate hydrates are prone to display needlelike
      morphology, and the axis diameter of the particles decreases with the increase of
      reaction temperature and pH value. With the further increase of the reaction
      temperature (333-368 K) and pH value, the sheetlike crystallites become the
      preferred morphology, and at higher temperatures and pH values, these
      crystallites tend to assemble into layerlike structures with diverse
      morphologies, such as spherical-like particles with rosette-like structure and
      cakelike particles built from sheetlike structure. Fourier transform infrared (FT
      IR) spectra show that these various morphologies are closely related to their
      compositions. The needlelike magnesium carbonate hydrate has a formula of
      MgCO3.xH2O, in which the value x is greatly affected by the experimental
      conditions, whereas with the morphological transformation from needlelike to
      sheetlike structure, their corresponding compositions also change from MgCO3.xH2O
      to Mg5(CO3)4(OH)2.4H2O in the interval of 328-333 K.

PMID- 16805602
TI  - Investigation of electrodeposition of Bi2Te3 nanowires into nanoporous alumina
      templates with a rotating electrode.
AB  - A rotating electrode was employed to investigate the electrodeposition of Bi2Te3
      nanowires. We found that mass transport of electrolytes into alumina templates of
      high aspect ratio plays a significant role in determining the properties of the
      obtained wires since diffusion is the rate-determining mechanism of mass
      transport within these nanochannels. In addition to slow growing rate, the effect
      of mass transport causes a slight composition variation from the bottom to the
      top of the wires. With a rotating electrode, the composition variation along the
      wires can be reduced by shortening the concentration depleted zone from the bulk
      electrolyte to the opening of pores. The wire growing rate can consequently be
      increased. Moreover, the wire compositions were confirmed to be adjustable by
      varying the rotation speed under the limitation of using a thin template.

PMID- 16805603
TI  - Aqueous solution route to high-aspect-ratio zinc oxide nanostructures on indium
      tin oxide substrates.
AB  - High-aspect-ratio ZnO nanowires and nanotubes are formed on indium tin oxide
      (ITO) substrates using a three-step route at low temperatures. The three steps,
      including successive ionic layer absorption and reaction (SILAR) deposition of
      the ZnO seed layer, hydrothermal annealing of the seed layer, and chemical bath
      deposition (CBD) of the one-dimensional (1D) ZnO nanostructures, are all
      conducted in aqueous solutions at temperatures below 120 degrees C. Both the
      hydrothermal annealing of the SILAR seed layer and the low-concentration
      precursor solution employed in the CBD process are crucial in order to synthesize
      the uniform and high-aspect-ratio ZnO nanostructures on the ITO substrate. TEM
      analyses reveal that both the nanowire and the nanotube possess the single
      crystal structure and are grown along [001] direction. Room-temperature
      cathodoluminescence spectrum of the 1D ZnO nanostructures shows a sharp
      ultraviolet emission at 375 nm and a broad green-band emission.

PMID- 16805604
TI  - XPS valence characterization of lithium salts as a tool to study
      electrode/electrolyte interfaces of Li-ion batteries.
AB  - X-ray photoelectron valence spectra of lithium salts LiBF4, LiPF6, LiTFSI, and
      LiBETI have been recorded and analyzed by means of density functional theory
      (DFT) calculations, with good agreement between experimental and calculated
      spectra. The results of this study are used to characterize electrode/electrolyte
      interfaces of graphite negative electrodes in Li-ion batteries using organic
      carbonate electrolytes containing LiTFSI or LiBETI salts. By a combined X-ray
      photoelectron spectroscopy (XPS) core peaks/valence analysis, we identify the
      main constituents of the interface. Differences in the surface layers'
      composition can be evidenced, depending on whether LiTFSI or LiBETI is used as
      the lithium salt.

PMID- 16805605
TI  - Electron spin resonance studies on the oxidation mechanism of sterically hindered
      cyclic amines in TiO2 photocatalytic systems.
AB  - A sterically hindered cyclic amine, 4-hydroxy-2,2,6,6-tetramethylpiperidine
      (HTMP), is converted to the corresponding aminoxyl radical (nitroxide radical), 4
      hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (TEMPOL radical) as a result of a
      photocatalytic reaction in TiO2 aqueous suspension. The time profile of the
      radical formation and the effect of additives, such as SCN-, I-, methanol, and
      H2O2, on the initial formation rate were measured in order to elucidate the
      reaction mechanism. The experimental observations indicated that the direct
      photocatalytic oxidation of HTMP followed by reaction with O2 is the dominant
      process in the formation of TEMPOL radicals. Electrochemical measurements showed
      that HTMP is oxidized at 0.7 V (vs NHE), which is consistent with the proposed
      mechanism. The possibility of other processes, involving reactions with singlet
      molecular oxygen, superoxide radical, and hydroxyl radical, were excluded from
      the reaction mechanism.

PMID- 16805606
TI  - Efficient fabrication and enhanced photocatalytic activities of 3D-ordered films
      of titania hollow spheres.
AB  - Facile and effective approaches were developed to fabricate 3D-ordered films of
      titania hollow spheres with different sphere diameters. The shell thickness of
      the sphere was adjusted in the range of 20-40 nm by changing the casting cycle of
      the titania precursor. The photonic stop band was observed for the 3D-ordered
      film and was tunable by the sphere diameter and the shell thickness. The stop
      band shifted from 930 to 547 nm. Crystal violet dye adsorbed on the film
      exhibited more than two times higher absorbance than that on a reference film of
      a flat titania layer, probably due to the red edge effect of the stop band and/or
      to the multiple scattering effect. The enhanced absorbance led to more efficient
      photodegradation of the dye under visible light and under solar light
      irradiation. A maximum photocatalytic enhancement of 22% is achieved. Finally,
      the influence of TiO2 morphology on photocatalytic activity was discussed.
      Compared with flat titania films, the existence of ordered macropores in titania
      spheres causes the stop band and a longer optical path due to multiple
      scattering. Both the red edge of the stop band and multiple scattering effects
      enhance the absorption of the dye, which results in the photocatalytic
      enhancement.

PMID- 16805607
TI  - Investigating internal structural differences between micelles and unilamellar
      vesicles of decanoic acid/sodium decanoate.
AB  - We report on the dynamics of a chromophore sequestered within the nonpolar
      regions of micelles and unilamellar vesicles comprised of decanoic acid/sodium
      decanoate. We find that there is a measurable difference in the motional dynamics
      of the chromophore perylene in these two nonpolar media, with the vesicle
      structure forming a somewhat less viscous environment than the micelle. In all
      cases, the chromophore reorients as a prolate rotor, implying a local environment
      with a nominally similar shape for both micelle and vesicle structures. These
      findings demonstrate that the organization of micelles is measurably different
      than that of bilayers.

PMID- 16805608
TI  - Synthesis and characterization of Pt0 nanoparticles in imidazolium ionic liquids.
AB  - The controlled decomposition of Pt2(dba)3 (dba = dibenzylideneacetone) dispersed
      in 1-n-butyl-3-methylimidazolium tetrafluoroborate (BMI.BF4) and
      hexafluorophosphate (BMI.PF6) ionic liquids in the presence of cyclohexene by
      molecular hydrogen produces Pt0 nanoparticles. The formation of these
      nanoparticles follows the two-step [A --> B, A + B --> 2B (k1, k2)] autocatalytic
      mechanism. The catalytic activity in the hydrogenation of cyclohexene is
      influenced by the nature of the anion rather than the mean-diameter of the
      nanoparticles. Thus, higher catalytic activity was obtained with Pt0 dispersed in
      BMI.BF4 containing the less coordinating anion although these nanoparticles
      possess a larger mean diameter (3.4 nm) than those obtained in BMI.PF6 (2.3 nm).
      Similar mean diameter values were estimated from in situ XRD and SAXS. XPS
      analyses clearly show the interactions of the ionic liquid with the metal surface
      demonstrating the formation of an ionic liquid protective layer surrounding the
      platinum nanoparticles. SAXS analysis indicated the formation of a semi-organized
      ionic liquid layer surrounding the metal particles with an extended molecular
      length of around 2.8 nm in BMI.BF4 and 3.3 nm in BMI.PF6.

PMID- 16805609
TI  - Gold and gold-iron oxide magnetic glyconanoparticles: synthesis, characterization
      and magnetic properties.
AB  - The preparation, characterization and the magnetic properties of gold and gold
      iron oxide glyconanoparticles (GNPs) are described. Glyconanoparticles were
      prepared in a single step procedure in the presence of aqueous solution of thiol
      functionalized neoglycoconjugates and either gold salts or both gold and iron
      salts. Neoglycoconjugates of lactose and maltose disaccharides with different
      linkers were used. Iron-free gold or gold-iron oxide GNPs with controlled gold
      iron ratios were obtained. The average core-size diameters are in the range of
      1.5-2.5 nm. The GNPs are fully characterized by (1)H NMR spectrometry,
      transmission electron microscopy (TEM), and UV-vis and X-ray absorption (XAS)
      spectroscopies. Inductive plasma-atomic emission spectrometry (ICP) and elemental
      analysis gave the average number of neoglycoconjugates per cluster. The magnetic
      properties were measured in a SQUID magnetometer. The most remarkable results was
      the observation of a permanent magnetism up to room temperature in the iron-free
      gold GNPs, that was not present in the corresponding gold-iron oxide GNPs.

PMID- 16805610
TI  - Carbon nanotube network formation from evaporating sessile drops.
AB  - Fabrication of single-walled carbon nanotube (SWNT) networks using evaporation of
      SDS-SWNT sessile drops on a hydrophobized silicon substrate is reported. It is
      suggested that the organization of nanotubes during evaporation is controlled by
      aggregates (in the SDS-SWNT dispersion) and hydrophobicity of the substrate. On
      hydrophobic substrates, the evaporation of SDS-SWNT sessile drops proceeds
      through constant contact area. On hydrophilic substrates, nanotube aggregates in
      SDS-SWNT dispersion stop the contact line from moving, resulting in the formation
      of "coffee-stains". The (partial) removal of aggregates by centrifugation is
      essential for a freely moving contact line leading to the organization of
      nanotubes into a network of homogeneously distributed nanotubes on the most
      hydrophobic substrate. The evaporation of sessile drops was characterized by
      microscopic, spectroscopic, and topographical techniques.

PMID- 16805611
TI  - Ozonization at the vacancy defect site of the single-walled carbon nanotube.
AB  - The ozonization at the vacancy defect site of the single-walled carbon nanotube
      has been studied by static quantum mechanics and atom-centered density matrix
      propagation based ab initio molecular dynamics within a two-layered ONIOM
      approach. Among five different reaction pathways at the vacancy defect, the
      reaction involving the unsaturated active carbon atom is the most probable
      pathway, where ozone undergoes fast dissociation at the active carbon atom at 300
      K. Complementary to the experiments, our work provides a microscopic
      understanding of the ozonization at the vacancy defect site of the single-walled
      carbon nanotube.

PMID- 16805612
TI  - Preparation of nanosheet polyethylene with heterogeneous metallocene catalyst and
      formation mechanism of nanosheet polyethylene.
AB  - Silica with small and regular pore sizes was synthesized by hydrothermal
      crystallization and investigated with thermogravimetric analysis, X-ray
      diffraction, Fourier transform infrared spectroscopy, N2 adsorption-desorption,
      and scanning electron microscopy (SEM). The ethylene polymerization was carried
      out with the silica-supported metallocene catalyst, and the morphology of the
      resultant polyethylene was investigated with SEM. It was found that the silica
      could break up into sheet fragments instantaneously during polymerization and the
      polyethylene could replicate it to obtain nanosheet polyethylene. A possible
      formation mechanism of the nanosheet polyethylene is proposed.

PMID- 16805613
TI  - What can you learn from a molecular probe? New insights on the behavior of C343
      in homogeneous solutions and AOT reverse micelles.
AB  - The behavior of C343, a common molecular probe utilized in solvation dynamics
      experiments, was studied in homogeneous media and in aqueous and nonaqueous
      reverse micelles (RMs). In homogeneous media, the Kamlet and Taft solvatochromic
      comparison method quantified solute-solvent interactions from the absorption and
      emission bands showing that the solvatochromic behavior of the dye depends not
      only on the polarity of the medium but also on the hydrogen-bonding properties of
      the solvent. Specifically, in the ground state the molecule displays a
      bathochromic shift with the polarity polarizability (pi) and the H-bond acceptor
      (beta) ability of the solvents and a hypsochromic shift with the hydrogen donor
      ability (alpha) of the media. The carboxylic acid group causes C343 to display
      greater sensitivity to the beta than to the pi polarity parameter; this
      sensitivity increases in the excited state, while the dependence on alpha
      vanishes. This demonstrates that C343 forms a stable H-bond complex with solvents
      with high H-bond acceptor ability (high beta) and low H-bond donor character (low
      alpha). Spectroscopy in nonpolar solvents reveals J-aggregate formation. With
      information from the Kamlet-Taft analysis, C343 was used to explore RMs composed
      of water or polar solvents/sodium 1,4-bis-2-ethylhexylsulfosuccinate
      (AOT)/isooctane using absorption, emission, and time-resolved spectroscopies.
      Sequestered polar solvents included ethylene glycol (EG), formamide (FA), N,N
      dimethylformamide (DMF), and N,N-dimethylacetamide (DMA). Dissolved in the AOT RM
      systems at low concentration, C343 exists as a monomer, and when introduced to
      the RM samples in its protonated form, C343 remains protonated driving it to
      reside in the interface rather than the water pool. The solvathochromic behavior
      of the dye depends the specific polar solvent encapsulated in the RMs, revealing
      different types of interactions between the solvents and the surfactant. EG and
      water H-bond with the AOT sulfonate group destroying their bulk H-bonded
      structures. While water remains well segregated from the nonpolar regions, EG
      appears to penetrate into the oil side of the interface. In aqueous AOT RMs, C343
      interacts with neither the sulfonate group nor the water, perhaps because of
      intramolecular H-bonding in the dye. DMF and DMA interact primarily through
      dipole-dipole forces, and the strong interactions with AOT sodium counterions
      destroy their bulk structure. FA also interacts with the Na+ counterions but
      retains its H-bond network present in bulk solvent. Surprisingly, FA appears to
      be the only polar solvent other than water forming a "polar-solvent pool" with
      macroscopic properties similar to the bulk.

PMID- 16805614
TI  - Selective coalescence of bubbles in simple electrolytes.
AB  - Simple ions in electrolytes exhibit different degrees of affinity for the
      approach to the free surface of water. This results in strong ion-specific
      effects that are particularly dramatic in the selective inhibition of bubble
      coalescence. I present here the calculation of electrostatic interaction between
      free surfaces of electrolytes caused by the ion accumulation or depletion near a
      surface. When both anion and cation are attracted to the surface (like H+ and Cl-
      in HCl solutions), van der Waals attraction facilitates approach of the surfaces
      and the coalescence of air bubbles. When only an anion or cation is attracted to
      the surface (like Cl- in NaCl solutions), an electric double layer forms,
      resulting in repulsive interaction between free surfaces. I applied the method of
      effective potentials (evaluated from published ion density profiles obtained in
      simulations) to calculate the ionic contribution to the surface-surface
      interaction in NaCl and HCl solutions. In NaCl, but not in HCl, the double-layer
      interaction creates a repulsive barrier to the approach of bubbles, in agreement
      with the experiments. Moreover, the concentration where ionic repulsion in NaCl
      becomes comparable in magnitude to the short-range hydrophobic attraction
      corresponds to the experimentally found transition region toward the inhibition
      of coalescence.

PMID- 16805615
TI  - Raman spectroscopic study on the structure in the surface and the bulk shell of
      Ce(x)Pr(1-x)O(2-delta) mixed oxides.
AB  - The difference between the surface and the bulk shell of Ce(x)Pr(1-x)O(2-delta)
      mixed oxides was studied by Raman spectroscopy with four different excitation
      lasers. Two Raman peaks appear at 465 and 570 cm(-1) under all of the four
      lasers. The former is attributed to the Raman active F(2g) mode of CeO2, while
      the latter is attributed to oxygen vacancy. On the basis of the fact that the
      laser with shorter wavelength is closer to the electronic adsorption of samples,
      it is found that the Raman information detected by excitation laser with shorter
      wavelength is more sensitive to the surface region of samples. An inflection is
      observed in the relationship of the value I570/I465 to the Ce content in
      Ce(x)Pr(1-x)O(2-delta). With the increase in the wavelength of excitation laser,
      the Ce content corresponding to the inflection decreases. Combined with the
      surface concentration obtained by XPS, it can be deduced that the composition of
      Ce(x)Pr(1-x)O(2-delta) mixed oxide particles in the surface region and the bulk
      shell are different, the former is enrichment of Pr component and the latter is
      enrichment of Ce component. The thickness of the surface layer with rich Pr
      component decreases with the increase in the Ce content.

PMID- 16805616
TI  - Fabrication of highly antireflective silicon surfaces with superhydrophobicity.
AB  - Highly antireflective porous silicon surfaces with superhydrophobicity were
      obtained by means of chemical etching and fluoroalkylsilane self-assembly. The
      results show that wettability and reflectivity of these surfaces strongly depend
      on the etching method and the resultant surface morphology. All of the four
      resultant porous silicon surfaces by alkaline etching, acidic etching, thick Pt
      assisted acidic etching, and thin Pt-assisted acidic etching can reduce
      reflectance, but the efficiency differs greatly. Except for the alkaline etching,
      the porous silicon surfaces produced by the other three etching methods can reach
      superhydrophobicity after fluoroalkylsilane modification. These differences are
      due to the different surface morphology and roughness. Moreover, the porous
      silicon surface produced by thin Pt-assisted acidic etching presents abundant
      holes and particles with diameters ranging from nanometers to submicrometers.
      This morphology enables the porous silicon surface to own a very low reflectance
      value that is averaged to be about 3% over the whole experimental photon
      wavelength spanning 300-800 nm.

PMID- 16805617
TI  - The [BMI][Tf2N] ionic liquid/water binary system: a molecular dynamics study of
      phase separation and of the liquid-liquid interface.
AB  - We report molecular dynamics (MD) simulations of the aqueous interface of the
      hydrophobic [BMI][Tf2N] ionic liquid (IL), composed of 1-butyl-3
      methylimidazolium cations (BMI+) and bis(trifluoromethylsulfonyl)imide anions
      (Tf2N-). The questions of water/IL phase separation and properties of the neat
      interface are addressed, comparing different liquid models (TIP3P vs TIP5P water
      and +1.0/-1.0 vs +0.9/-0.9 charged IL ions), the Ewald vs the reaction field
      treatments of the long range electrostatics, and different starting conditions.
      With the different models, the "randomly" mixed liquids separate much more slowly
      (in 20 to 40 ns) than classical water-oil mixtures do (typically, in less than 1
      ns), finally leading to distinct nanoscopic phases separated by an interface, as
      in simulations which started with a preformed interface, but the IL phase is more
      humid. The final state of water in the IL thus depends on the protocol and
      relates to IL heterogeneities and viscosity. Water mainly fluctuates in
      hydrophilic basins (rich in O(Tf2N) and aromatic CH(BMI) groups), separated by
      more hydrophobic domains (rich in CF3(Tf2N) and alkyl(BMI) groups), in the form
      of monomers and dimers in the weakly humid IL phase, and as higher aggregates
      when the IL phase is more humid. There is more water in the IL than IL in water,
      to different extents, depending on the model. The interface is sharper and
      narrower (approximately 10 A) than with the less hydrophobic [BMI][PF6] IL and is
      overall neutral, with isotropically oriented molecules, as in the bulk phases.
      The results allow us to better understand the analogies and differences of
      aqueous interfaces with hydrophobic (but hygroscopic) ILs, compared to classical
      organic liquids.

PMID- 16805618
TI  - Interaction of phenothiazine compounds with zwitterionic lysophosphatidylcholine
      micelles: Small angle X-ray scattering, electronic absorption spectroscopy, and
      theoretical calculations.
AB  - In this work, small-angle X-ray scattering (SAXS) studies on the interaction of
      the phenothiazine cationic compounds trifluoperazine (TFP, 2-10 mM) and
      chlorpromazine (CPZ, 2-10 mM) with micelles of the zwitterionic surfactant L
      alpha-lysophosphatidylcholine (LPC, 30 mM), at pHs 4.0 and 7.0, are reported. The
      SAXS results demonstrate that, upon addition of both phenothiazines, the LPC
      micelle of prolate ellipsoidal shape changes into a cylindrically shaped micelle,
      increasing its axial ratio from 1.6 +/- 0.1 (in the absence of drug) to 2.5 +/-
      0.1 (for 5 and 10 mM of phenothiazine). Such an effect is accompanied by a
      shrinking of the paraffinic shortest semiaxis from 22.5 +/- 0.3 to 20.0 +/- 0.5
      A. Besides, a significant increase in polar shell electron density from 0.39(1)
      to 0.45(1) e/A3 is observed, consistent with cylinder-like aggregate geometry.
      Moreover, an increase of the phenothiazine concentration induces the appearance
      of a repulsive interference function over the SAXS curve of zwitterionic
      micelles, which is typical of interaction between surface-charged micelles. Such
      a finding provides evidence that the positively charged phenothiazine molecule
      must be accommodated near the hydrophobic/hydrophilic inner micellar interface in
      such a way that a net surface charge is altered with respect to the original
      overall neutral zwitterionic micelle. Such phenothiazine location is favored by
      both electrostatic and hydrophobic contributions, giving rise to binding constant
      values, obtained from electronic absorption results, that are quite larger
      compared to their binding to another zwitterionic surfactant, 3-(N-hexadecyl-N,N
      dimethylammonio)propanesulfonate (HPS) (Caetano, W., et al. J. Colloid Int. Sci.
      2003, 260, 414-422). Comparisons are made by means of theoretical calculations of
      the surfactant headgroup dipole moments for monomers of LPC and HPS. The
      theoretical results show that the dipole moment in LPC is almost perpendicular to
      the methylene chain, while a significant contribution along the methylene chain
      occurs for HPS. Besides, evidence is presented for extensive delocalization of
      the charges in the headgroups, which could be also relevant for the binding of
      the drugs.

PMID- 16805619
TI  - Oxidation and melting of aluminum nanopowders.
AB  - Recently, nanometer-sized aluminum powders became available commercially, and
      their use as potential additives to propellants, explosives, and pyrotechnics has
      attracted significant interest. It has been suggested that very low melting
      temperatures are expected for nanosized aluminum powders and that such low
      melting temperatures could accelerate oxidation and trigger ignition much earlier
      than for regular, micron-sized aluminum powders. The objective of this work was
      to investigate experimentally the melting and oxidation behavior of nanosized
      aluminum powders. Powder samples with three different nominal sizes of 44, 80,
      and 121 nm were provided by Nanotechnologies Inc. The particle size distributions
      were measured using small-angle X-ray scattering. Melting was studied by
      differential scanning calorimetry where the powders were heated from room
      temperature to 750 degrees C in an argon environment. Thermogravimetric analysis
      was used to measure the mass increase indicative of oxidation while the powders
      were heated in an oxygen-argon gas mixture. The measured melting curves were
      compared to those computed using the experimental particle size distributions and
      thermodynamic models describing the melting temperature and enthalpy as functions
      of the particle size. The melting behavior predicted by different models
      correlated with the experimental observations only qualitatively. Characteristic
      stepwise oxidation was observed for all studied nanopowders. The observed
      oxidation behavior was well interpreted considering the recently established
      kinetics of oxidation of micron-sized aluminum powders. No correlation was found
      between the melting and oxidation of aluminum nanopowders.

PMID- 16805620
TI  - Structures of 17,19-hexatriacontadiyne monolayers on Au(111) studied by infrared
      reflection absorption spectroscopy and scanning tunneling microscopy.
AB  - The aggregation and reaction of 17,19-hexatriacontadiyne molecules are studied on
      a Au(111) surface. The molecular orientation and arrangement are elucidated by
      infrared reflection absorption spectroscopy (IRAS) and scanning tunneling
      microscopy (STM). A vapor-deposited monolayer and a multilayered film formed by
      adsorption from the solution provide IRA spectra with bands due to the
      antisymmetric and symmetric stretching of methylenes in the gauche conformation.
      After the adsorbed film is rinsed with the solvent, however, the spectrum loses
      the gauche bands and is characterized by the enhanced C-H(distal) and C
      H(proximal) stretching bands, which means that all-trans molecules are laid flat.
      Only STM images for the rinsed film display columnar structures on the
      herringbones of the reconstructed Au(111) surface; the alkyl chain direction is
      found to be parallel to the Au atom row. The results indicate that an ordered
      monolayer is formed first at the liquid-solid interface, and then, disordered
      overlayers with the gauche conformation are grown but removed by a rinse. Upon
      exposure to UV light, thus obtained monomer columns are converted into oligomers
      with flexible backbones and an increased gauche population in the alkyl chains,
      which resemble red phase polydiacetylenes in LB films.

PMID- 16805621
TI  - Efficient overall water splitting under visible-light irradiation on (Ga(1
      x)Zn(x))(N(1-x)O(x)) dispersed with Rh-Cr mixed-oxide nanoparticles: Effect of
      reaction conditions on photocatalytic activity.
AB  - The photocatalytic activity of (Ga(1-x)Zn(x))(N(1-x)O(x)) loaded with Rh-Cr mixed
      oxide (Rh(2-y)Cr(y)O3) nanoparticles for overall water splitting under visible
      light irradiation (lambda > 400 nm) is investigated with respect to reaction pH
      and gas pressure. The photocatalytic performance of the catalyst is found to be
      strongly dependent on the pH of the reactant solution but largely independent of
      gas pressure. The present photocatalyst exhibits stable and high photocatalytic
      activity in an aqueous solution of pH 4.5 for 72 h. The photocatalytic
      performance is much lower at pH 3.0 and pH 6.2, attributable to corrosion of the
      cocatalyst and hydrolysis of the catalyst. The dispersion of Rh(2-y)Cr(y)O3 as a
      cocatalyst on the (Ga(1-x)Zn(x))(N(1-x)O(x)) surface promotes hydrogen evolution,
      which is considered to be the rate-determining step for overall water splitting
      on this catalyst.

PMID- 16805622
TI  - Cosolvent effects on the micellization of oxyphenyl(copoly)ethylene oxide
      copolymers in aqueous solution.
AB  - In the present paper, we have analyzed how the presence of ethanol affects the
      micellization process of two structurally related polyoxyethylene block
      copolymers with diblock and triblock architectures (diblock, S15E63; triblock,
      E67S15E67) and the same hydrophobic block length, formed by oxyphenylethylene
      units, through surface tension, static and dynamic light scattering, density,
      ultrasound velocity, transmission electron microscopy, and steady-state
      fluorescence techniques. E and S denote the oxyethylene (-OCH2CH2) and
      oxyphenylethylene (-OCH2CH(C6H5)) units, respectively, and the subscripts the
      block length. The effect of increasing amounts of ethanol in solution gives rise
      to a progressive disruption of the micelle structures formed by these copolymers,
      with an increase in the critical micelle concentration (cmc) values and a
      decrease in the micellar aggregation number. This originated from the deswelling
      of the poly(ethylene oxide) (PEO) chains due to a decrease of the water content,
      accompanied by a reduction of the solvophobicity and an increase of the
      solubility of the S blocks, causing the lowering of the interfacial tension
      between the polyoxyphenylethylene core and the solvent, and favoring the swelling
      of hydrophobic blocks. Therefore, to achieve thermodynamic equilibrium, the
      micelle size should be smaller. A model derived from small angle neutron
      scattering (SANS) data is also applied to get extra information on micelle
      structure. With the aim of obtaining information about the hydration of micellar
      solutions of these block copolymers, compressibility and fluorescence data were
      collected. The increase of compressibility with ethanol addition confirms the
      swelling of the hydrophobic polyoxyphenylethylene chains. Fluorescence data show
      that the addition of ethanol to the solution decreases the polarity, favoring the
      solubilization of the oxyphenylethylene chains in the mixed solvent as single
      monomers. Aggregation data derived from this technique are in fair agreement with
      those obtained from light scattering.

PMID- 16805623
TI  - Adsorption of microstructured particles at liquid-liquid interfaces.
AB  - The solid particles are adsorbed at interfaces and form self-assembled structures
      when the particles have suitable wettability to both liquids. Here, we show
      theoretically how the microstructure on the particle surface affects their
      adsorption properties. The physical properties of the interface adsorbing a
      particle will be described by taking into account the surface roughness due to
      the microstructure. The microstructure on the surface changes drastically the
      wettability and the equilibrium position of the adsorbed particle. Therefore, the
      contact angle of the particle at the three-phase contact line shifts with the
      particle surface area, because the surface roughness enhances the interfacial
      properties of the particle surface. Moreover, the range of the interfacial
      tensions at which the particle is adsorbed becomes narrower with the increase of
      the surface roughness. The effect of the particle shape on the adsorption
      properties is also studied. In the case of disk-shaped particles, the energy
      changes discontinuously when the plane surface of the particle contacts the
      liquid-liquid interface. The adsorbing position does not change with the surface
      roughness. The orientation of a parallelepiped particle at the liquid-liquid
      interface is governed by the aspect ratio and the surface area of the particle.
      On the other hand, the particle which is partially covered with the
      microstructured surface is adsorbed firmly at the interface in an oriented state.
      We should consider not only the interfacial tensions but also the surface
      structure and the particle shape to control the adsorption behavior of the
      particle.

PMID- 16805624
TI  - Trimethylamine as a probe molecule to differentiate acid sites in Y-FAU zeolite:
      FTIR study.
AB  - In heterogeneous catalysis acidity has a very important influence on activity and
      selectivity: correct determination of acidic properties is a base to improve
      industrial processes. The aim of this work was to study trimethylamine (TMA) as a
      probe molecule able to distinguish between the different Bronsted acid sites in
      zeolitic frameworks. Our work mainly focused on faujasite-type zeolites because
      the HY zeolite is one of the most used acidic catalysts in industrial processes.
      In this paper, typical IR bands assigned to TMA-protonated species (formed in
      supercages) are detected in the HY zeolite. TMA interacting by hydrogen bonding
      with the acid sites located in the sodalite units is also observed. The
      wavenumbers of some typical IR bands assigned to TMA-protonated species appear to
      depend on the acidic strength, and a complementary study with ZSM-5 and X-FAU
      samples confirms this proposition.

PMID- 16805625
TI  - Application of the statistical rate theory of interfacial transport to interpret
      the relaxation time of proton adsorption from solution onto oxides.
AB  - A new way to analyze the rate of hydrogen ion adsorption from solution onto
      oxides was described. The statistical rate theory of interfacial transport (SRT)
      was applied to interpret relaxation time of ion adsorption. The new procedure for
      determination of rate constants of surface reaction was compared with the
      classical theory of activated adsorption and desorption (TAAD). It was found that
      for adsorption of uncharged species, both models give the same result, but for
      ion adsorption, their predictions differ considerably. Influence of surface
      potential and total concentration of adsorption sites on calculated rate
      constants was also discussed.

PMID- 16805626
TI  - Quantification of the effect of 4-tert-butylpyridine addition to I-/I3- redox
      electrolytes in dye-sensitized nanostructured TiO2 solar cells.
AB  - Addition of 4-tert-butylpyridine (4TBP) to redox electrolytes used in dye
      sensitized TiO2 solar cells has a large effect on their performance. In an
      electrolyte containing 0.7 M LiI and 0.05 M I2 in 3-methoxypropionitrile,
      addition of 0.5 M 4TBP gave an increase of the open-circuit potential of 260 mV.
      Using charge extraction and electron lifetime measurements, this increases could
      be attributed to a shift of the TiO2 band edge toward negative potentials
      (responsible for 60% of the voltage increase) and to an increase of the electron
      lifetime (40%). At a lower 4TBP concentration the shift of the band edge was
      similar, but the effect on the electron lifetime was less pronounced. The working
      mechanism of 4TBP can be summarized as follows: (1) 4TBP affects the surface
      charge of TiO2 by decreasing the amount of adsorbed protons and/or Li+ ions. (2)
      It decreases the recombination of electrons in TiO2 with triiodide in the
      electrolyte by preventing triiodide access to the TiO2 surface and/or by
      complexation with iodine in the electrolyte.

PMID- 16805627
TI  - Computer studies on the effects of long chain alcohols on sodium dodecyl sulfate
      (SDS) molecules in SDS/dodecanol and SDS/hexadecanol monolayers at the air/water
      interface.
AB  - Molecular dynamics simulations of sodium dodecyl sulfate (SDS)/dodecanol and
      SDS/hexadecanol monolayers at the air/water interface were investigated where the
      monolayer mixtures were prepared by two different configurations. In the first
      configuration, all of the dodecanol (or hexadecanol) molecules were placed
      together and also the SDS molecules were placed together in the surface area. In
      the second configuration, the dodecanol (or hexadecanol) molecules were uniformly
      distributed with the SDS molecules, forming a homogeneous mixture. The results
      showed that the alcohol tails are more ordered and thicker than the SDS tails in
      monolayers where the alcohol molecules are close to each other and separated from
      the SDS. However, the reverse trend is observed in monolayers where the SDS and
      alcohol molecules are well mixed; that is, the alcohol tails seem to have less
      order. Studies of how the SDS tails are affected by the presence of long chain
      alcohols are also discussed. Basically, by increasing the alcohol chain length,
      the order and the thickness of the SDS tails increased when those molecules were
      placed all together in a region of the surface area. When both surfactants were
      well mixed, the order and thickness of the SDS chains decreased as the alcohol
      chain length increased. Comparisons of the present results with actual
      experiments of similar systems were performed, and they showed similar
      tendencies.

PMID- 16805628
TI  - Visible light-induced degradation of ethylene glycol on nitrogen-doped TiO2
      powders.
AB  - The photocatalytic degradation processes of ethylene glycol (EG) during the UV or
      visible light irradiation of pure anatase and nitrogen (N)-doped TiO2 powders
      (TiO(2-x)N(x), x = 0, 0.002, 0.003, and 0.007) were investigated using time
      resolved diffuse reflectance (TDR) and solid-state NMR spectroscopies. The TDR
      spectra and time traces observed for the charge carriers indicated that the
      scavenging of photogenerated holes (h+) by EG occurred during the 355-nm laser
      photolysis of the N-doped TiO2 powders, while no direct oxidation reaction of EG
      by h+ occurred during the 460-nm laser photolysis, although the charge carriers
      were sufficiently generated upon excitation. The solid-state magic-angle spinning
      (MAS) NMR measurements revealed that EG is preferentially chemisorbed on the
      surface of the N-doped TiO2 powders, in contrast to the pure TiO2, and degrades
      under visible light irradiation.

PMID- 16805629
TI  - New-generation amber united-atom force field.
AB  - We have developed a new-generation Amber united-atom force field for simulations
      involving highly demanding conformational sampling such as protein folding and
      protein-protein binding. In the new united-atom force field, all hydrogens on
      aliphatic carbons in all amino acids are united with carbons except those on
      Calpha. Our choice of explicit representation of all protein backbone atoms aims
      at minimizing perturbation to protein backbone conformational distributions and
      to simplify development of backbone torsion terms. Tests with dipeptides and
      solvated proteins show that our goal is achieved quite successfully. The new
      united-atom force field uses the same new RESP charging scheme based on B3LYP/cc
      pVTZ//HF/6-31g** quantum mechanical calculations in the PCM continuum solvent as
      that in the Duan et al. force field. van der Waals parameters are empirically
      refitted starting from published values with respect to experimental solvation
      free energies of amino acid side-chain analogues. The suitability of mixing new
      point charges and van der Waals parameters with existing Amber covalent terms is
      tested on alanine dipeptide and is found to be reasonable. Parameters for all new
      torsion terms are refitted based on the new point charges and the van der Waals
      parameters. Molecular dynamics simulations of three small globular proteins in
      the explicit TIP3P solvent are performed to test the overall stability and
      accuracy of the new united-atom force field. Good agreements between the united
      atom force field and the Duan et al. all-atom force field for both backbone and
      side-chain conformations are observed. In addition, the per-step efficiency of
      the new united-atom force field is demonstrated for simulations in the implicit
      generalized Born solvent. A speedup around two is observed over the Duan et al.
      all-atom force field for the three tested small proteins. Finally, the efficiency
      gain of the new united-atom force field in conformational sampling is further
      demonstrated with a well-known toy protein folding system, an 18 residue
      polyalanine in distance-dependent dielectric. The new united-atom force field is
      at least a factor of 200 more efficient than the Duan et al. all-atom force field
      for ab initio folding of the tested peptide.

PMID- 16805630
TI  - Glyme-lithium salt phase behavior.
AB  - Phase diagrams are reported for glyme mixtures with simple lithium salts. The
      glymes studied include monoglyme (DME), diglyme, triglyme, and tetraglyme. The
      lithium salts include LiBETI, LiAsF6, LiI, LiClO4, LiBF4, LiCF3SO3, LiBr, LiNO3,
      and LiCF3CO2. The phase diagrams clearly illustrate how solvate formation and
      thermophysical properties are dictated by the ionic association strength of the
      salt (i.e., the properties of the anions) and chain length of the solvating
      molecules. This information provides critical predictive capabilities for solvate
      formation and ionic interactions common in organometallic reagents and battery
      electrolytes.

PMID- 16805631
TI  - Dynamical arrest of electron transfer in liquid crystalline solvents.
AB  - We argue that electron transfer reactions in slowly relaxing solvents proceed in
      the nonergodic regime, making the reaction activation barrier strongly dependent
      on the solvent dynamics. For typical dielectric relaxation times of polar
      nematics, electron transfer reactions in the subnanosecond time scale fall into
      nonergodic regime in which nuclear solvation energies entering the activation
      barrier are significantly lower than their thermodynamic values. The transition
      from isotropic to nematic phase results in weak discontinuities of the solvation
      energies at the transition point and the appearance of solvation anisotropy
      weakening with increasing solute size. The theory is applied to analyze
      experimental kinetic data for the electron transfer kinetics in the isotropic
      phase of 5CB liquid crystalline solvent. We predict that the energy gap law of
      electron transfer reactions in slowly relaxing solvents is characterized by
      regions of fast change of the rate at points where the reaction switches between
      the ergodic and nonergodic regimes. The dependence of the rate on the donor
      acceptor separation may also be affected in a way of producing low values for the
      exponential falloff parameter.

PMID- 16805632
TI  - Phase equilibria in carbon dioxide expanded solvents: Experiments and molecular
      simulations.
AB  - We present complementary molecular simulations and experimental results of phase
      equilibria for carbon dioxide expanded acetonitrile, methanol, ethanol, acetone,
      acetic acid, toluene, and 1-octene. The volume expansion measurements were done
      using a high-pressure Jerguson view cell. Molecular simulations were performed
      using the Gibbs ensemble Monte Carlo method. Calculations in the canonical
      ensemble (NVT) were performed to determine the coexistence curve of the pure
      solvent systems. Binary mixtures were simulated in the isobaric-isothermal
      distribution (NPT). Predictions of vapor-liquid equilibria of the pure components
      agree well with experimental data. The simulations accurately reproduced
      experimental data on saturated liquid and vapor densities for carbon dioxide,
      methanol, ethanol, acetone, acetic acid, toluene, and 1-octene. In all carbon
      dioxide expanded liquids (CXL's) studied, the molecular simulation results for
      the volume expansion of these binary mixtures were found to be as good as, and in
      many cases superior to, predictions based on the Peng-Robinson equation of state,
      demonstrating the utility of molecular simulation in the prediction of CXL phase
      equilibria.

PMID- 16805633
TI  - Structure and phase behavior of self-assembled DPPC-DNA-metal cation complexes.
AB  - Multilamellar liposomes of dipalmitoylphosphatidylcholine (DPPC) in solution with
      DNA and bivalent metal cations (Ca2+, Mn2+, Mg2+) self-assemble into a ternary
      DPPC-DNA-Me2+ complex. The supramolecular structure of the complex consists of an
      ordered multilamellar assembly where hydrated DNA helices are sandwiched between
      the lipid bilayers and the metal cations bind the phosphate groups of DNA to the
      lipid polar heads. In the range of explored incubation times, the complex
      coexists with the uncomplexed DPPC over the whole temperature range investigated
      (20-55 degrees C). Accordingly, two distinct coexisting lamellar phases are
      observed, one corresponding to the ternary complex and the other to the
      uncomplexed lipid. The structure and thermotropic phase behavior of both of these
      have been investigated by means of synchrotron X-ray diffraction, and the
      relevant structural data are deduced from experimental electron density profiles.
      While the uncomplexed lipid exhibits the same phase behavior as pure DPPC, that
      is, L beta'-P beta'-L alpha, the thermotropic behavior of the bound lipid in the
      complex is partially altered. This is manifested as an increase in the main
      transition temperature and the disappearance of the ripple phase leading to the
      single -phase transition. The role of the different metal cations in promoting
      and stabilizing the DNA condensation into the ternary complex is also discussed.

PMID- 16805634
TI  - A detailed look at vesicle fusion.
AB  - Many different hypotheses on the molecular mechanisms of vesicle fusion exist.
      Because these mechanisms cannot be readily asserted experimentally, we address
      the problem by a coarse-grained molecular dynamics simulations study and compare
      the results with the results of other techniques. The simulations performed
      include the fusion of small and large vesicles and exocytosis, i.e., the fusion
      of small vesicles with flat bilayers. We demonstrate that the stalk, the initial
      contact between two fusing vesicles, is initiated by lipid tails that extend
      spontaneously. The stalk is revealed to be composed of the contacting monolayers
      only, yet without hydrophobic voids. Anisotropic and radial expansion of the
      stalk have been theorized; we show that stalk evolution can proceed via both
      pathways starting from similar setups and that water triggers the transition from
      elongated stalk to hemifusion diaphragm.

PMID- 16805635
TI  - Experimental phase diagram of symmetric binary colloidal mixtures with opposite
      charges.
AB  - The phase behavior of equimolar mixtures of oppositely charged colloidal systems
      with similar absolute charges is studied experimentally as a function of the salt
      concentration in the system and the colloid volume fraction. As the salt
      concentration increases, fluids of irreversible clusters, gels, liquid-gas
      coexistence, and finally, homogeneous fluids, are observed. Previous simulations
      of similar mixtures of Derjaguin-Landau-Verwey-Overbeek (DLVO) particles indeed
      showed the transition from homogeneous fluids to liquid-gas separation, but also
      predicted a reentrant fluid phase at low salt concentrations, which is not found
      in the experiments. Possibly, the fluid of clusters could be caused by a
      nonergodicity transition responsible for the gel phase in the reentrant fluid
      phase. Liquid-gas separation takes a delay time after the sample is prepared,
      whereas gels collapse from the beginning. The density of the liquid in
      coexistence with a vapor phase depends linearly on the overall colloid density of
      the system. The vapor, on the other hand, is comprised of equilibrium clusters,
      as expected from the simulations.

PMID- 16805636
TI  - Characterization of supramolecular polyphenol-chromium(III) clusters by molecular
      dynamics simulations.
AB  - The binding of Cr(III) with (2R,3S,4R)-(+)-3,3',4,4',7-flavanpentol in aqueous
      solution is investigated by atomistic molecular dynamics simulations
      concentrating the analysis of the sampled data on the polyphenol ability to
      chelate metal ions and to form large noncovalently bonded molecular and
      supramolecular architectures.

PMID- 16805637
TI  - Environment-controlled interchromophore charge transfer transitions in dipeptides
      probed by UV Absorption and electronic circular dichroism spectroscopy.
AB  - Charge transfer (CT) transitions between the C-terminal carboxylate and peptide
      group have been investigated for alanyl-X and X-alanine dipeptides by far-UV
      absorption and electronic circular dichroism (ECD) spectroscopy (where X
      represents different amino acid residues). The spectra used in the present study
      were obtained by subtracting the spectrum of the cationic species from that of
      the corresponding zwitterionic peptide spectrum. These spectra displayed three
      bands, e.g., band I between 44 and 50 kK (kK = 10(3) cm(-1)), band II at 53 kK,
      and band III above 55 kK, which were, respectively, assigned to a n(COO-) --> pi*
      CT transition, a pi(COO-) --> pi* CT transition, and a carboxylate pi --> pi*
      (NV1) transition, respectively By comparison of the intensity, bandwidth, and
      wavenumber position of band I of some of the investigated dipeptides, we found
      that positive charges on the N-terminal side chain (for X = K), and to a minor
      extent also the N-terminal proton, reduce its intensity. This can be understood
      in terms of attractive Coulomb interactions that stabilize the ground state over
      the charge transfer state. For alanylphenylalanine, we assigned band I to a n(COO
      ) --> pi* CT transition into the aromatic side chain, indicating that aromatic
      side chains interact electronically with the backbone. We also performed ECD
      measurements at different pH values (pH 1-6) for a selected subset of XA and AX
      peptides. By subtraction of the pH 1 spectrum from that observed at pH 6, the ECD
      spectrum of the CT transition was obtained. A titration curve of their spectra
      reveals a substantial dependence on the protonation state of the aspartic acid
      side chain of AD, which is absent in DA and AE. This most likely reflects a
      conformational transition of the C-terminus into a less extended state, though
      the involvement of a side chain --> peptide CT transition cannot be completely
      ruled out.

PMID- 16805638
TI  - g-Anisotropy of the S2-state manganese cluster in single crystals of
      cyanobacterial photosystem II studied by W-band electron paramagnetic resonance
      spectroscopy.
AB  - The multiline signal from the S2-state manganese cluster in the oxygen evolving
      complex of photosystem II (PSII) was observed in single crystals of a
      thermophilic cyanobacterium Thermosynechococcus vulcanus for the first time by W
      band (94 GHz) electron paramagnetic resonance (EPR). At W-band, spectra were
      characterized by the g-anisotropy, which enabled the precise determination of the
      tensor. Distinct hyperfine splittings (hfs's) as seen in frozen solutions of PSII
      at X-band (9.5 GHz) were detected in most of the crystal orientations relative to
      the magnetic field. In some orientations, however, the hfs's disappeared due to
      overlapping of a large number of EPR lines from eight crystallographic symmetry
      related sites of the manganese cluster within the unit cell of the crystal.
      Analysis of the orientation-dependent spectral features yielded the following g
      tensor components: g(x) = 1.988, g(y) = 1.981, g(z) = 1.965. The principal values
      suggested an approximate axial symmetry around the Mn(III) ion in the cluster.

PMID- 16805639
TI  - Role of monovalent counterions in the ultrafast dynamics of DNA.
AB  - This paper examines the contribution of counterion motion to the electric-field
      dynamics in the interior of DNA. The electric field is measured by a coumarin
      fluorophore that is synthetically incorporated into an oligonucleotide, where it
      replaces a native base pair. The DNA is a 17-base-pair oligomer with no A- or G
      tracts. Time-resolved Stokes-shift measurements on the coumarin are made from 40
      ps to 40 ns with each of the alkali ions and or one of several tetraalkylammonium
      ions as the DNA counterion. With the possible exception of rubidium, there are no
      indications of site-specific binding of the counterions. For sodium and other
      ions with a smaller hydrodynamic radius, the dynamics are identical and are fit
      to a power law. For larger ions, there is a progressive increase in the rate of
      shifting after 1 ns. This effect correlates with the hydrodynamic radius of the
      counterion. The lack of change in the spectral shape of the emission shows that
      neither the broadly distributed power-law relaxation nor the extra nanosecond
      dynamics are due to heterogeneity in the relaxation rates of different helices.

PMID- 16805640
TI  - Elastic bag model for molecular dynamics simulations of solvated systems:
      application to liquid water and solvated peptides.
AB  - The fluctuating elastic boundary (FEB) model for molecular dynamics has recently
      been developed and validated through simulations of liquid argon. In the FEB
      model, a flexible boundary which consists of particles connected by springs is
      used to confine the solvated system, thereby eliminating the need for periodic
      boundary conditions. In this study, we extend this model to the simulation of
      bulk water and solvated alanine dipeptide. Both the confining potential and
      boundary particle interaction functions are modified to preserve the structural
      integrity of the boundary and prevent the leakage of the solute-solvent system
      through the boundary. A broad spectrum of structural and dynamic properties of
      liquid water are computed and compared with those obtained from conventional
      periodic boundary condition simulations. The applicability of the model to
      biomolecular simulations is investigated through the analysis of conformational
      population distribution of solvated alanine dipeptide. In most cases we find
      remarkable agreement between the two simulation approaches.

PMID- 16805641
TI  - Spectroscopic study of substrate binding to the carbonmonoxy form of
      dehaloperoxidase from Amphitrite ornata.
AB  - Dehaloperoxidase (DHP) is a globular heme enzyme found in the marine worm
      Amphitrite ornata that can catalyze the dehalogenation of halophenols to the
      corresponding quinones by using hydrogen peroxide as a cosubstrate. Its three
      dimensional fold is surprisingly similar to that of the oxygen storage protein
      myoglobin (Mb). A key structural feature common to both DHP and Mb is the
      existence of multiple conformations of the distal histidine. In DHP, the
      conformational flexibility may be involved in promotion of substrate and
      cosubstrate entry and exit. Here we have explored the dynamics of substrate
      binding in DHP using Fourier transform infrared spectroscopy and flash
      photolysis. A number of discrete conformations at the active site were identified
      from the appearance of multiple CO absorbance bands in the infrared region of the
      spectrum. Upon photolysis at cryogenic temperatures, the CO molecules are trapped
      at docking sites within the protein matrix, as inferred from the appearance of
      several photoproduct bands characteristic of each site. Substrate binding
      stabilizes the protein by approximately 20 kJ/mol. The low yield of substrate
      bound DHP at ambient temperature points toward a steric inhibition of substrate
      binding by carbon monoxide.

PMID- 16805642
TI  - Vibrational spectroscopy and normal-mode analysis of Fe(II) octaethylporphyrin.
AB  - The normal-mode spectrum for the four-coordinated heme compound Fe(II)
      octaethylporphyrin, Fe(OEP), has been determined by refining force constants to
      the experimental Fe vibrational density of states measured with nuclear resonance
      vibrational spectroscopy (NRVS). Convergence of the calculated spectrum to the
      data was achieved by first imposing D4 symmetry on the model structure as well as
      the force constants, progressively including different internal coordinates of
      motion, then allowing the true Ci (or S2) point group symmetry of the C(i)1
      Fe(OEP) crystal structure. The NRVS-refined normal modes are in good agreement
      with Raman and IR spectra at high frequencies. Prior density functional theory
      predictions for a model porphyrin are similar to the core modes computed with the
      best-fit force field, but significant differences between D4 and Ci modes
      underline the sensitivity of porphyrin Fe normal modes to structural details.
      Some differences between the Ci best fit and the NRVS data can be attributed to
      intermolecular contacts not included in the normal-mode analysis.

PMID- 16805643
TI  - Formation of methane hydrate from polydisperse ice powders.
AB  - Neutron diffraction runs and gas-consumption experiments based on pressure-volume
      temperature measurements are conducted to study the kinetics of methane hydrate
      formation from hydrogenated and deuterated ice powder samples in the temperature
      range of 245-270 K up to high degrees of transformation. An improved theory of
      the hydrate growth in a polydisperse ensemble of randomly packed ice spheres is
      developed to provide a quantitative interpretation of the data in terms of
      kinetic model parameters. This paper continues the research line of our earlier
      study which was limited to the monodisperse case and shorter reaction times
      (Staykova et al., 2003). As before, we distinguish the process of initial hydrate
      film spreading over the ice particle surface (stage I) and the subsequent hydrate
      shell growth (stage II) which includes two steps, i.e., an interfacial
      clathration reaction and the gas and water transport (diffusion) through the
      hydrate layer surrounding the shrinking ice cores. Although kinetics of hydrate
      formation at stage II is clearly dominated by the diffusion mechanism which
      becomes the limiting step at temperatures above 263 K, both steps are shown to be
      essential at lower temperatures. The permeation coefficient D is estimated as
      (1.46 +/- 0.44) x 10(-12) m2/h at 263 K with an activation energy Q(D)
      approximately 52.1 kJ/mol. This value is close to the energy of breaking hydrogen
      bonds in ice Ih and suggests that this process is the rate-limiting step in
      hydrate formation from ice in the slower diffusion-controlled part of the
      reaction.

PMID- 16805644
TI  - Emission from charge recombination during the pulse radiolysis of
      arylethynylpyrenes.
AB  - Emission from several 1-(arylethynyl)pyrenes with a substituent on the aryl group
      (REPy, R = phenyl (PEPy), 4-dimethylaminophenyl (NPEPy), 4-isopropoxyphenyl
      (OPEPy), 2-quinonyl (QEPy), and 9-(10-cyanoanthracenyl) (AEPy)) was studied with
      time-resolved fluorescence measurements during pulse radiolysis in benzene. NPEPy
      and AEPy showed only monomer emission, while PEPy, OPEPy, and QEPy showed both
      monomer and excimer emissions during pulse radiolysis. In addition, REPy's also
      showed long-lived emissions with very weak intensities in the absence of oxygen,
      which were assigned to the "P-type" delayed fluorescence derived from the triplet
      triplet annihilation. The formation of REPy's in the singlet excited state
      (1REPy*) can be interpreted as the charge recombination between the REPy radical
      cation and anion (REPy*+ and REPy*-, respectively), which are initially generated
      from the radiolytic reaction in benzene. Both the highest occupied molecular
      orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of PEPy are
      localized on the 1-pyrenyl (Py) moiety, while the HOMO of REPy's with an electron
      donating or withdrawing substituent on the benzene ring (R(D)EPy such as NPEPy
      and OPEPy or R(A)EPy such as QEPy and AEPy) is mainly localized on the donor
      moieties (R(D) or Py) and the LUMO on the acceptor ones (Py or R(A),
      respectively). Therefore, it is suggested that the one-electron oxidation and
      reduction of REPy's can occur from the donor and acceptor moieties, respectively.
      This scheme reasonably explains the relationship between the annihilation
      enthalpy changes (-Delta H' degrees) for the charge recombination of REPy*+ and
      REPy*- and the singlet excitation energies (E'(S1) of the REPy's. The results are
      compared with those in electrogenerated chemiluminescence.

PMID- 16805647
TI  - Ancient host-pathogen associations maintained by specificity of chemotaxis and
      antibiosis.
AB  - Switching by parasites to novel hosts has profound effects on ecological and
      evolutionary disease dynamics. Switching requires that parasites are able to
      establish contact with novel hosts and to overcome host defenses. For most host
      parasite associations, it is unclear as to what specific mechanisms prevent
      infection of novel hosts. Here, we show that parasitic fungal species in the
      genus Escovopsis, which attack and consume the fungi cultivated by fungus-growing
      ants, are attracted to their hosts via chemotaxis. This response is host
      specific: Escovopsis spp. grow towards their natural host cultivars more rapidly
      than towards other closely related fungi. Moreover, the cultivated fungi secrete
      compounds that can suppress Escovopsis growth. These antibiotic defenses are
      likewise specific: in most interactions, cultivars can inhibit growth of
      Escovopsis spp. not known to infect them in nature but cannot inhibit isolates of
      their naturally infecting pathogens. Cases in which cultivars are susceptible to
      novel Escovopsis are limited to a narrow set of host-parasite strain
      combinations. Targeted chemotactic and antibiotic responses therefore explain why
      Escovopsis pathogens do not readily switch to novel hosts, consequently
      constraining long-term dynamics of host-parasite coevolution within this ancient
      association.

PMID- 16805648
TI  - Moving toward assured access to treatment in microbicide trials. Global Campaign
      for Microbicides.

PMID- 16805649
TI  - Reducing disparities in the burden of cancer: the role of patient navigators.

PMID- 16805650
TI  - Building surgical research capacity in Africa: the Ptolemy Project.

PMID- 16805651
TI  - Regulation of clinical research sponsored by pharmaceutical companies: a
      proposal.

PMID- 16805653
TI  - Warning signs for suicide: theory, research, and clinical applications.
AB  - The current article addresses the issue of warning signs for suicide, attempting
      to differentiate the construct from risk factors. In accordance with the
      characteristic features discussed, a consensus set of warning signs identified by
      the American Association of Suicidology working group are presented, along with a
      discussion of relevant clinical and research applications.

PMID- 16805654
TI  - Warning signs for suicide on the Internet: a descriptive study.
AB  - The issue of suicide warning signs on the Internet is considered. In addition to
      reviewing some of the relevant conceptual issues about warning signs, a random
      sample of Internet sites was selected and reviewed. Warning signs were grouped
      and agreement across sites was examined, with results confirming broad disparity
      in what is presented to the public. The implications of a lack of consensus on
      warning signs for suicide are discussed.

PMID- 16805655
TI  - A test of the effectiveness of a list of suicide warning signs for the public.
AB  - In this study we examined the effect that reading a list of warning signs for
      suicide has on beliefs about suicide, including the belief that one can recognize
      a suicidal crisis. All participants read two sets of warning signs (with only the
      experimental group reading the suicide warning signs) and then answered questions
      concerning beliefs related to three health problems. Results indicate that
      participants who read the suicide warning signs reported greater abilities to
      recognize if someone is suicidal but did not report stronger beliefs that
      suicidal individuals are partly to blame, nor did they report lower likelihoods
      of befriending suicidal individuals. Results suggest that reading the list of
      warning signs may be effective in increasing the public's ability to recognize
      suicidal crises without creating or magnifying stigmatizing beliefs about
      suicidal individuals.

PMID- 16805656
TI  - The emotional impact and ease of recall of warning signs for suicide: a
      controlled study.
AB  - In light of concerns about potential iatrogenic effects of information about
      suicide, in the current study we examined the emotional impact of reading a list
      of warning signs for suicide in comparison to comparable lists for heart attacks
      and diabetes. All participants read two sets of warning signs, with the
      experimental group reading the suicide warning signs. Results confirm no
      difference in emotional impact across groups, along with providing evidence that
      warning signs for suicide are as easy to recall after exposure as warning signs
      for heart attack. Implications for pubic health campaigns are discussed.

PMID- 16805657
TI  - Imminent suicide: the illusion of short-term prediction.
AB  - The concept of imminent suicide is examined. A search of National Electronic
      Library for Mental Health, the Cochrane Library, PubMed, OVID and MD Consult
      databases was conducted using the terms "suicide, imminent." The term imminent
      frequently appears in the mental health literature, finding common usage among
      clinicians. It is also a legal term of art embedded in civil commitment statutes;
      duty to warn and protect statutes and case law, usually under the rubric of
      dangerousness; and in seclusion and restraint policies. Managed care admission
      protocols may contain imminence criteria for patients at risk for suicide before
      approving insurance benefits, yet no suicide risk factors exist for the short
      term prediction of suicide.

PMID- 16805658
TI  - The hospital management of fatal self-poisoning in industrialized countries: an
      opportunity for suicide prevention?
AB  - Suicide by self-poisoning is a prevalent cause of death worldwide. A substantial
      proportion of individuals who poison themselves come into contact with medical
      services before they die. Our focus in the current study was the medical
      management of drug self-poisoning in industrialized countries and its possible
      contribution to suicide prevention. We reviewed the literature to determine the
      proportion of self-poisoning suicides who reach hospital alive, the
      sociodemographic and clinical characteristics of in-hospital overdose deaths, the
      in-hospital management this group of patients receives, and whether there are
      specific aspects of pre-hospital care and in-hospital management that have the
      potential to improve survival. Between 11% and 28% of individuals who died
      following deliberate ingestion of drugs reached hospital alive. The substances
      which were most frequently implicated in death were paracetamol (acetaminophen)
      and paracetamol compounds, tricyclic antidepressants, and benzodiazepines. Most
      patients received fairly intensive treatment, yet death may have been preventable
      in a small proportion of cases. Only one intervention (the administration of
      acetylcysteine) was shown to reduce mortality and this was in a highly selected
      group of patients (those who had ingested paracetamol and developed fulminant
      hepatic failure). It is possible that other interventions such as better airway
      management, the prompt administration of activated charcoal, and improved pre
      hospital care may improve outcomes but their potential contribution to suicide
      prevention needs to be investigated in future studies.

PMID- 16805659
TI  - Interpersonal precipitants and suicide attempts in borderline personality
      disorder.
AB  - Borderline personality disorder (BPD) is often characterized by multiple low
      lethality suicide attempts triggered by seemingly minor incidents, and less
      commonly by high lethality attempts that are attributed to impulsiveness or
      comorbid major depression. The relationships among life events, impulsiveness,
      and type of suicidal behavior has hardly been studied in BPD and mood disorders.
      This study compared depressed attempters with and without BPD to identify
      specific suicide precipitants and risk factors in BPD and their relationship to
      severity of suicidal behavior. Attempters with comorbid BPD and major depressive
      disorder (MDD) had a higher number of lifetime suicide attempts; made their first
      attempt at a younger age; reported more interpersonal triggers; and had higher
      levels of lifetime aggression, hostility, and impulsivity, compared with
      attempters with major depression only. Environmental triggers of attempts in BPD
      are more likely to be interpersonal stressors. Lethality of attempts in BPD plus
      MDD is equal to that in MDD only, indicating that the seriousness of precipitants
      is unrelated to the lethality of the suicidal behavior. The differences between
      groups suggest that risk assessment and treatment should target both depression
      and personality disorder in those with combined illness.

PMID- 16805660
TI  - Suicidal and deliberate self-harm ideation among patients with physical illness:
      the role of coping styles.
AB  - The relationship between coping styles and suicidal ideation (SI) or deliberate
      self-harm (DSH) ideation among patients with physical illness was examined. Four
      hundred fifteen adult male medical inpatients completed the Coping Styles
      Questionnaire. Patients with and without SI, and with and without DSH, were
      compared on coping styles. Sixteen percent of patients (n = 67) had SI and 18.3%
      (n = 76) had DSH. SI was associated with higher scores on emotional coping and
      lower scores on rational and detachment coping styles, compared with those
      without SI. DSH, compared with those without DSH, was associated with
      significantly higher scores on avoidance coping strategies. These data suggest
      coping styles among medical patients with and without SI or DSH may differ. The
      mechanism of this link is not entirely clear, but it may be that coping styles
      reflect one possible pathway of the association between poor physical health and
      SI and DSH. Replication of these results in a longitudinal study is needed. If
      replicated, incorporation of these data into the development of intervention
      strategies focused on improving coping strategies may be worthwhile.

PMID- 16805661
TI  - Gender in suicide attempt rates and childhood sexual abuse rates: is there an
      interaction?
AB  - Two competing explanations for higher rates of attempted suicide in women than
      men were compared. Because childhood sexual abuse is more prevalent in girls than
      boys, one explanation of higher rates of suicide attempts in women is that it is
      a direct result of the higher incidence of sexual abuse in girls. Alternatively,
      higher rates of suicide attempts might result from gender differences in the
      impact of childhood sexual abuse on suicidal behavior. To compare these theories,
      data from 1,889 abstinent, substance-dependent patients who completed the
      Childhood Trauma Questionnaire (CTQ) and who were interviewed about suicide
      attempts was examined. Scores on each scale of the CTQ were examined as a
      function of gender and attempter status. Results showed higher rates of suicide
      attempts in women than in men, higher CTQ scores in women than men, and a higher
      CTQ score in attempters than nonattempters. However, logistic regression
      indicated that gender and abuse did not interact to determine attempter status.
      Thus, the data support the first hypothesis that the greater frequency of suicide
      attempts in women may be partly attributed to the higher prevalence of childhood
      sexual abuse in girls. The generalizability of these results to the general
      population and to other diagnostic groups requires further study.

PMID- 16805662
TI  - Predictors of suicidal ideation among "at risk" cocaine-using African American
      women.
AB  - The focus of this study was to identify factors that differentiate women drug
      abusers who had experienced suicidal ideation from those who did not. Face-to
      face interviews were conducted with 221 cocaine-using women in Atlanta, GA, 88
      (39.8%) of whom reported thinking about committing suicide at least once during
      the 90 days prior to interview and 133 (60.2%) of whom did not. Multivariate
      logistic regression was used to identify predictors of suicidal ideation, and
      post hoc goodness-of-fit tests were conducted to assess the robustness of final
      models derived. Model 1 excluded all psychosocial functioning measures and Model
      2 included these items. Both models showed that suicidal ideation was more common
      among women who were unemployed, had been abused sexually, engaged in sexual
      relations to cope with stresses, or had less helpful relatives. In addition,
      Model 1 revealed a heightened risk for women experiencing financial problems and
      those who had a previous mental health diagnosis, whereas Model 2 showed an
      elevated risk among women who experienced anxiety and those who had lower levels
      of self-esteem. These findings suggest the need for prevention and intervention
      programs that target at-risk women, and for such programs to include an emphasis
      on suicidal ideation in addition to focusing on risk factors that are addressed
      more commonly.

PMID- 16805663
TI  - Variation in functioning, psychosocial characteristics, and six-month outcomes
      among suicidal youth in comprehensive community mental health services.
AB  - In this study we compared the psychosocial (n = 7,896) and clinical (n = 4,664)
      characteristics and 6-month functional outcomes (n = 2,594) of suicidal and
      nonsuicidal youth. Repeat and previous attempters were more likely than first
      time and never attempters to experience psychosocial problems and to be
      functionally impaired in a variety of domains. Differences in functional
      impairment persisted at 6 months. Among those who were not severely functionally
      impaired at baseline, repeat attempters were more likely to be severely impaired
      at 6 months. Subgroups of suicide attempters may present to treatment
      differently, have a different expression of problems over time, and have
      different treatment needs.

PMID- 16805664
TI  - Facility-level characteristics associated with serious suicide attempts and
      deaths from suicide in juvenile justice residential facilities.
AB  - Little is known about how facility-level characteristics affect the risk of
      suicide and suicide attempts in juvenile justice residential facilities. This
      leaves facility administrators and mental health providers without evidence-based
      guidance on how the facility itself affects risks. The current study uses data
      from two recently developed censuses of juvenile justice facilities in the United
      States to examine the relationship between facility-level characteristics and the
      likelihood of a facility reporting serious suicide attempts and deaths from
      suicide. Results suggest highest risks for facilities housing larger populations
      of Black young people and for facilities locking sleeping room doors. Lower risks
      are found for facilities screening all young people within 24 hours of arrival.

PMID- 16805665
TI  - The molecular diversity of glycosaminoglycans shapes animal development.
AB  - Proteoglycans (PGs), molecules in which glycosaminoglycans (GAGs) are covalently
      linked to a protein core, are components of the extracellular matrix of all
      multicellular organisms. Sugar moieties in GAGs are often extensively modified,
      which make these molecules enormously complex. We discuss here the role of PGs
      during animal development, emphasizing the in vivo significance of sugar
      modifications. We explore a model in which the modification patterns of GAG
      chains may provide a specific code that contributes to the correct development of
      a multicellular organism.

PMID- 16805666
TI  - Cellular responses to DNA damage: one signal, multiple choices.
AB  - DNA double-strand breaks (DSBs) produce a number of cellular responses, some
      mutually exclusive. Depending on where on the chromosome it occurs, a DSB may
      become preserved inside a telomere or eliminated by repair. A cell may arrest
      division via checkpoint activation to fix DSBs or commit suicide by apoptosis.
      What determines the outcome: to bury, fix, or succumb to DNA DSBs? With this
      question in mind, we review recent data on cellular responses to DSBs.

PMID- 16805667
TI  - Surviving the breakup: the DNA damage checkpoint.
AB  - In response to even a single chromosomal double-strand DNA break, cells enact the
      DNA damage checkpoint. This checkpoint triggers cell cycle arrest, providing time
      for the cell to repair damaged chromosomes before entering mitosis. This
      mechanism helps prevent the segregation of damaged or mutated chromosomes and
      thus promotes genomic stability. Recent work has elucidated the molecular
      mechanisms underlying several critical steps in checkpoint activation, notably
      the recruitment of the upstream checkpoint kinases of the ATM and ATR families to
      different damaged DNA structures and the molecular events through which these
      kinases activate their effectors. Chromatin modification has emerged as one
      important component of checkpoint activation and maintenance. Following DNA
      repair, the checkpoint pathway is inactivated in a process termed recovery. A
      related but genetically distinct process, adaptation, controls cell cycle re
      entry in the face of unrepairable damage.

PMID- 16805668
TI  - The professional development of an entomologist.
AB  - An account of the development of biological interest, and specifically interest
      in bees, by Charles D. Michener. Included topics are the role of graduate
      students and the relationship between behavioral studies and systematics.
      Sections are (a) upbringing, including initiation of biological interests, (b)
      early studies of bees, (c) student work at the University of California,
      Berkeley, (d) work at the American Museum of Natural History and in the U.S.
      Army, and (e) work at the University of Kansas, especially wild bee behavior and
      bee systematics.

PMID- 16805670
TI  - Periodontal assessment by right- and left-handed examiners: is there a
      difference?
AB  - BACKGROUND: Multiple factors that influence the precision of periodontal probing
      measurements have been identified. These factors can be categorized as being
      dependent upon host-related, probe-related, or examiner-related variables.
      However, the potential influence of examiner handedness (right or left) on the
      measurement of periodontal probing depths (PDs) has not been addressed. The
      purpose of this study was to determine whether the measurements of PDs in the
      right and left quadrants are influenced by the handedness of the examiner.
      METHODS: Eight systemically healthy adult subjects with varying degrees of
      attachment loss and a minimum of 20 teeth were examined by five right-handed and
      five left-handed clinicians. The 10 clinicians were trained and calibrated for
      reproducible probe placement and angulation. PDs were measured using a
      conventional periodontal probe at six sites per tooth. Mean PD measurements were
      compared between right- and left-handed examiners using analysis of variance
      (ANOVA) with a random patient effect to correlate participant data and a random
      effect for the examiner. RESULTS: There was no statistical difference in the
      measurement of PDs between right- and left-handed examiners at various locations
      in the mouth (P>0.17 in all cases). Only three individual sites showed a
      statistically significantly different mean PD between right- and left-handed
      examiners (unadjusted P<0.05; differences at or near 0.5 mm). Overall, right
      handed examiners tended to record slightly higher PD measurements than left
      handed examiners, but this difference did not reach statistical significance.
      CONCLUSIONS: The handedness of the periodontal examiner does not appear to
      influence the recorded measurement of probing depths. This finding is relevant to
      those conducting clinical research involving assessment of periodontal status.

PMID- 16805671
TI  - The effects of anabolic androgenic steroid abuse on gingival tissues.
AB  - BACKGROUND: Anabolic androgenic steroid (AAS) is the familiar name for synthetic
      derivatives of the male sex hormone, testosterone. A large number of young adults
      abuse AAS to enhance performance and physical appearance. The aim of this study
      was to evaluate the effects of AAS abuse on the gingival tissues in a group of
      bodybuilders and weight lifters. METHODS: The test group was composed of 24
      athletes aged between 17 and 29 years who had been using AAS for >1 year. All
      subjects were clinically examined for plaque levels (plaque index), gingival
      inflammation (gingival index), and gingival enlargement. The results were
      compared to a control group of 20 bodybuilders who had never used AAS drugs and
      who matched for age, educational level, and oral habits according to the data
      obtained from the test group. RESULTS: Although there were no statistical
      differences between the plaque index (P>0.05) and gingival index (P>0.05) scores
      of the study group and the control group, the AAS abusers had statistically
      higher scores of gingival thickness, extent of gingival encroachment, and total
      gingival enlargement scores (P<0.001 each) compared to non-users. CONCLUSIONS:
      The results of this study have revealed that the prolonged use of AAS is closely
      associated with significant levels of gingival enlargement. Because recreational
      abuse and abuse in non-competitive sports seem to increase despite legislation,
      dentists and periodontists should be familiar with the adverse effects of these
      synthetic derivatives of testosterone on the gingival tissues.

PMID- 16805672
TI  - Bacterial profile and burden of periodontal infection in subjects with a
      diagnosis of acute coronary syndrome.
AB  - BACKGROUND: Periodontitis has been identified as a potential risk factor in
      cardiovascular diseases. It is possible that the stimulation of host responses to
      oral infections may result in vascular damage and the inducement of blood
      clotting. The aim of this study was to assess the role of periodontal infection
      and bacterial burden as an explanatory variable to the activation of the
      inflammatory process leading to acute coronary syndrome (ACS). METHODS: A total
      of 161 consecutive surviving cases admitted with a diagnosis of ACS and 161
      control subjects, matched with cases according to their gender, socioeconomic
      level, and smoking status, were studied. Serum white blood cell (WBC) counts,
      high- and low-density lipoprotein (HDL/LDL) levels, high-sensitivity C-reactive
      protein (hsC-rp) levels, and clinical periodontal routine parameters were
      studied. The subgingival pathogens were assayed by the checkerboard DNA-DNA
      hybridization method. RESULTS: Total oral bacterial load was higher in the
      subjects with ACS (mean difference: 17.4x10(5); SD: 10.8; 95% confidence interval
      [CI]: 4.2 to 17.4; P<0.001), and significant for 26 of 40 species including
      Porphyromonas gingivalis, Tannerella forsythensis, and Treponema denticola. Serum
      WBC counts, hsC-rp levels, Streptococcus intermedius, and Streptococcus sanguis,
      were explanatory factors to acute coronary syndrome status (Nagelkerke r2=0.49).
      CONCLUSION: The oral bacterial load of S. intermedius, S. sanguis, Streptococcus
      anginosus, T. forsythensis, T. denticola, and P. gingivalis may be concomitant
      risk factors in the development of ACS.

PMID- 16805673
TI  - Distribution of FcgammaRIIa and FcgammaRIIIb genotypes in patients with
      generalized aggressive periodontitis.
AB  - BACKGROUND: Polymorphisms in FcgammaR have been associated with different forms
      of periodontitis. This study determined the frequency of FcgammaRIIa and
      FcgammaRIIIb alleles/genotypes in patients with generalized aggressive
      periodontitis (GAgP). METHODS: Thirty-one GAgP and 49 periodontally healthy
      Brazilian subjects participated in the study. Full-mouth periodontal examinations
      were carried out, and mouthwash samples were collected for human DNA isolation.
      FcgammaR genotyping was performed by polymerase chain reaction and hybridization
      with allele-specific oligonucleotide probes. Significant differences between
      groups were sought by Mann-Whitney, chi2, and Fisher exact tests and configural
      frequency analysis. RESULTS: FcgammaRIIa-H131 (53.8%) and FcgammaRIIIb-NA1 (75%)
      were the most prevalent alleles in this sample population. A significant
      overrepresentation of FcgammaRIIIb-NA2 was observed in the GAgP group, whereas
      FcgammaRIIIb-NA1 was detected more often in healthy individuals (odds ratio,
      32.5; 95% confidence interval [CI], 10.6 to 99.8; P<0.001). No significant
      differences in the distribution of the FcgammaRIIa genotypes were observed
      between the groups. The prevalence of FcgammaRIIIb-NA2/NA2 was higher in GAgP
      patients, whereas FcgammaRIIIb-NA1/NA1 was predominant in the healthy group
      (chi2=45.1; P<0.001). The combination of the genotypes FcgammaRIIIb-NA2/NA2 plus
      FcgammaRIIa-H/H131 was observed more frequently in GAgP subjects than expected
      from marginal frequencies (chi2=12.5; P<0.001). CONCLUSIONS: The data suggest
      that the FcgammaRIIIb-NA2 allele and/or FcgammaRIIIb-NA2/NA2 genotype and the
      composite genotype FcgammaRIIIb-NA2/NA2 plus FcgammaRIIa-H/H131 may be associated
      with GAgP, whereas FcgammaRIIIb-NA1 and/or FcgammaRIIIb-NA1/NA1 may be related to
      periodontal health in this sample of the Brazilian population.

PMID- 16805674
TI  - Study design for calibration of clinical examiners measuring periodontal
      parameters.
AB  - BACKGROUND: We present an approach to examiner calibration study design where the
      number of calibration subjects is based on a specified margin of error (half
      width of the 95% confidence interval [CI]) of the percentage of agreement (exact
      and within 1 mm) for both intra- and interexaminer reliability assessments.
      METHODS: An experienced standard examiner (S) trained three dental hygienists (A,
      B, and C) in correct procedures for obtaining a variety of periodontal measures.
      Duplicate measurements of probing depth (PD [mm]) and the free gingival margin to
      the cemento-enamel junction (CEJ-GM [mm]) were obtained in a pilot study to
      design a formal examiner calibration study, where sample sizes were adjusted for
      the effects of within-subject clustering of binary indices of agreement. RESULTS:
      Within-subject clustering of agreement indices resulted in an approximate four
      fold increase in the variance of the estimates of percentage of agreement with
      the standard. PD and CEJ-GM percentage of exact agreement measurements (95% CI)
      for each examiner-standard pair, respectively, were as follows: AS=55% (48%, 61%)
      and 70% (62%, 78%); BS=52% (45%, 59%) and 73% (63%, 82%); and CS=55% (50%, 61%)
      and 72% (65%, 79%). The corresponding 95% CIs unadjusted for the effects of
      clustering underestimated the margin of error associated with the estimates of
      exact agreement by as much as 57% for PD and 68% for CEJ-GM. CONCLUSION: Failure
      to account for dependence among site-level agreement indices results in a false
      sense of precision in the resulting reliability estimates and can lead to faulty
      inference.

PMID- 16805675
TI  - Development of a compact and simple gas chromatography for oral malodor
      measurement.
AB  - BACKGROUND: Volatile sulfur compounds (VSCs) in oral air are the only type of
      gases correlated with the strength of oral malodor. We developed a compact and
      simple gas chromatograph (GC) equipped with a newly invented indium oxide
      semiconductor gas sensor (SCS) for measuring the concentrations of VSCs in mouth
      air. We have assessed the correlation between measurements with a GC-SCS and
      those with a regular GC. METHODS: Oral air samples from randomly selected
      volunteers were analyzed with both a GC-SCS and a GC with a flame photometric
      detector (FPD), which is specific to VSCs, and GC-SCS measurements were compared
      to those obtained by GC-FPD. Subsequently, oral air samples before and after
      mouthrinsing with 5% ethanol mouthwash were analyzed to determine the effect of
      ethanol on VSC measurements by GC-SCS. RESULTS: There were strong correlations
      between VSC concentrations determined using these two gas chromatography methods
      (hydrogen sulfide, R=0.821, P<0.0001; methyl mercaptan, R=0.870, P<0.0001; and
      dimethyl sulfide, R=0.770, P<0.0001). Although GC-SCS can differentiate ethanol
      and VSCs in oral air samples after mouthrinsing, GC-SCS measurements demonstrated
      higher values than those obtained by GC-FPD; however, this discrepancy improved
      over time due to the reduced effect of ethanol. CONCLUSION: The results suggest
      that GC-SCS may be useful for the diagnosis of halitosis.

PMID- 16805676
TI  - Gingival recession treatment with connective tissue grafts in smokers and non
      smokers.
AB  - BACKGROUND: Cigarette smoking can adversely affect the results of many
      periodontal procedures. The purpose of this study was to determine whether
      cigarette smoking affects wound healing of subepithelial connective tissue
      grafts. METHODS: Seventeen systemically healthy patients with 22 Miller Class I
      or II mucogingival defects were divided into a non-smoker group or smoker group.
      Patients were regarded as smokers if they reported smoking 10 to 20 cigarettes
      per day. The following parameters were documented at the surgery date and 3 and 6
      months postoperatively: recession depth (RD), recession width (RW), keratinized
      gingiva height measured apico-coronally (KG), relative attachment level (RAL),
      probing depths (PD), bleeding on probing (BOP), and the full-mouth plaque score
      (FMP). Salivary cotinine samples were taken at the surgery to confirm the smoking
      history and to quantify cigarette use. RESULTS: Non-smokers (0- to 10-ng/ml
      cotinine level) healed with statistically more recession coverage than the
      smokers (>10-ng/ml cotinine level) (98.3% versus 82.3%, respectively; P=0.001).
      Six months postoperatively, the non-smokers healed with a 0.2-mm mean recession
      depth compared to a 1.0-mm mean recession depth for the smokers. This difference
      in recession depth was statistically significant (P=0.014). CONCLUSIONS: Root
      coverage with connective tissue grafts appears to be negatively associated with
      cigarette smoking. Smokers should consider smoking cessation or reducing the use
      of cigarettes for optimal results with connective tissue grafts.

PMID- 16805677
TI  - Effect of interleukin-1beta on transforming growth factor-beta and bone
      morphogenetic protein-2 expression in human periodontal ligament and alveolar
      bone cells in culture: modulation by avocado and soybean unsaponifiables.
AB  - BACKGROUND: In periodontal disease, interleukin-1beta (IL-1beta) is responsible
      for the matrix breakdown through excessive production of degrading enzymes by
      periodontal ligament fibroblasts and osteoblasts. Transforming growth factor-beta
      (TGF-beta) plays an important role in tissue regeneration as one of the factors
      capable of counteracting IL-1beta effects. In this study, we investigated the in
      vitro effect of avocado and soya unsaponifiables (ASU) on the expression of TGF
      beta1, TGF-beta2, and bone morphogenetic protein-2 (BMP-2) by human periodontal
      ligament (HPL) and human alveolar bone (HAB) cells in the presence of IL-1beta.
      METHODS: HPL and HAB cells were incubated for 48 hours with ASU (10 microg/ml) in
      the presence or absence of IL-1beta (10 ng/ml). The steady-state levels of TGF
      beta1, TGF-beta2, and BMP-2 mRNAs were determined by Northern blot or reverse
      transcription-polymerase chain reaction (RT-PCR). The amounts of TGF-beta1 and
      TGF-beta2 proteins were measured by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The data indicated that IL-1beta strongly decreases the expression of
      TGF-beta1 and TGF-beta2 by HPL cells. ASU were capable of opposing the cytokine
      effect. In HAB cells, TGF-beta1 and BMP-2 mRNA levels were downregulated by the
      cytokine. ASU were found to reverse the IL-1beta-inhibiting effect. In contrast,
      the cytokine stimulated the production of TGF-beta2 in alveolar bone cells, with
      no significant effect of ASU. CONCLUSIONS: The results indicate that the IL-1beta
      driven erosive effect in periodontitis could be enhanced by a decreased
      expression of members of the TGF-beta family. The ASU stimulation of TGF-beta1,
      TGF-beta2, and BMP-2 expression may explain their promoting effects in the
      treatment of periodontal disorders, at least partly. These findings support the
      hypothesis that ASU could exert a preventive action on the deleterious effects
      exerted by IL-1beta in periodontal diseases.

PMID- 16805678
TI  - Effect of EDTA root conditioning on the healing of intrabony defects treated with
      an enamel matrix protein derivative.
AB  - BACKGROUND: Regenerative periodontal therapy with an enamel matrix protein
      derivative (EMD) has been shown to promote regeneration in intrabony periodontal
      defects. However, in most clinical studies, root surface conditioning with EDTA
      was performed in conjunction with the application of EMD, and, therefore, it
      cannot be excluded that the results may also be attributable to the effect of the
      root conditioning procedure. The purpose of this study was to determine the
      effect of root conditioning on the healing of intrabony defects treated with EMD.
      METHODS: Twenty-four patients, each of whom exhibited one deep intrabony defect,
      were randomly treated with either open flap debridement (OFD) followed by root
      surface conditioning with EDTA and application of EMD (OFD+EDTA+EMD) or with OFD
      and application of EMD only (OFD+EMD). The following parameters were recorded at
      baseline and at 1 year: plaque index (PI), gingival index (GI), bleeding on
      probing (BOP), probing depth (PD), and clinical attachment level (CAL). RESULTS:
      No differences in any of the investigated parameters were observed at baseline
      between the two groups. Healing was uneventful in all patients. At 1 year after
      therapy, the OFD+EDTA+EMD group showed a reduction in mean PD from 9.3+/-1.3 mm
      to 4.0+/-0.9 mm (P<0.001), and mean CAL changed from 10.8+/-2.2 mm to 7.1+/-2.8
      mm (P<0.001). In the OFD+EMD group, mean PD was reduced from 9.3+/-1.2 mm to
      4.2+/-0.9 mm (P<0.001), and a change in mean CAL from 11.0+/-1.7 mm to 7.3+/-1.6
      mm (P<0.001). There were no significant differences in any of the investigated
      parameters between the two groups. CONCLUSION: In intrabony defects, regenerative
      surgery including OFD+EDTA+EMD failed to show statistically significant
      differences in terms of PD reduction and CAL gain compared to treatment with
      OFD+EMD.

PMID- 16805679
TI  - Severity of periodontal disease and number of remaining teeth are related to the
      prevalence of myocardial infarction and hypertension in a study based on 4,254
      subjects.
AB  - BACKGROUND: During the past 15 years, mounting evidence for the association
      between periodontal and cardiovascular disease has been presented in
      epidemiological studies. The aim of this study was to investigate how the
      severity of periodontal disease and number of remaining teeth relates to
      myocardial infarction (MI) and hypertension (HT). METHODS: Self-reported history
      of HT and MI was collected in 3,352 patients referred to the Department of
      Periodontology, Gavle County Hospital, and in 902 subjects randomly selected from
      the general population. Severity of periodontitis was estimated by a combination
      of the amount of bone loss around each tooth investigated from a full-mouth x
      ray, the presence or absence of bleeding on probing (BOP), and involvement of
      furcations. RESULTS: The severity of periodontitis was significantly associated
      with HT (prevalence 16%; P<0.0005), even after adjustment for age, gender, number
      of teeth, and smoking in the total sample, and with MI (prevalence 1.7%, P<0.03)
      after above-mentioned adjustments, but in middle-aged (40 to 60 years) subjects
      only. The number of diseased periodontal pockets was related to HT only
      (P<0.0001), and this relationship remained after the above-mentioned adjustments.
      The number of teeth was associated with MI (P<0.03) even after correction for
      age, gender, and smoking but was not related to hypertension. CONCLUSIONS: The
      severity of periodontal disease was related to HT independent of age but to the
      prevalence of MI in middle-aged subjects only. The number of diseased pockets was
      significantly related to HT only. On the other hand, the number of teeth was
      associated with the prevalence of MI independent of age but not to HT. These data
      support the view that oral health is related to cardiovascular disease in a dose
      dependent manner.

PMID- 16805680
TI  - Periodontal status in men with hypergonadotropic hypogonadism: effects of
      testosterone deficiency.
AB  - BACKGROUND: The purpose of this clinical study was to evaluate the possible
      influence of testosterone hormone on common clinical measurements of periodontal
      disease in men with hypergonadotropic hypogonadism. METHODS: Twenty-four
      hypergonadotropic hypogonadal men (H) and 24 systemically healthy men (S) were
      divided into two groups as chronic periodontitis and clinically healthy controls
      after clinical examinations and radiographs. The H group consisted of 12 control
      (H/C) and 12 chronic periodontitis (H/P) patients, and the S group consisted of
      12 control (S/C) and 12 chronic periodontitis (S/P) patients. Plaque index (PI),
      gingival index (GI), bleeding on probing (BOP), probing depth (PD), and clinical
      attachment loss (CAL) scores were recorded. RESULTS: The mean of all clinical
      parameters (PI, GI, BOP, PD, and CAL) were significantly (P<0.05) higher in
      periodontitis groups (H/P and S/P) than controls (H/C and S/C). There were no
      significant differences in the PD and CAL scores between periodontitis groups
      (S/P and H/P). The mean of GI and BOP scores were statistically higher in the H/P
      group than the S/P group (P<0.05). There was a negative correlation between GI
      and free testosterone levels (r=-0.794; P<0.05). CONCLUSION: According to these
      results, serum testosterone levels may possibly influence periodontal disease in
      men, and testosterone may have an inhibitory effect on gingival inflammation.

PMID- 16805681
TI  - The effect of rhBMP-2 around endosseous implants with and without membranes in
      the canine model.
AB  - BACKGROUND: Bone morphogenetic protein (BMP) is a potent differentiating agent
      for cells of the osteoblastic lineage. It has been used in the oral cavity under
      a variety of indications and with different carriers. However, the optimal
      carrier for each indication is not known. This study examined a synthetic
      bioabsorbable carrier for BMP used in osseous defects around dental implants in
      the canine mandible. METHODS: Twelve canines had their mandibular four premolars
      and first molar teeth extracted bilaterally. After 5 months, four implants were
      placed with standardized circumferential defects around the coronal 4 mm of each
      implant. One-half of the defects received a polylactide/glycolide (PLGA) polymer
      carrier with or without recombinant human BMP-2 (rhBMP-2), and the other half
      received a collagen carrier with or without rhBMP-2. Additionally, one-half of
      the implants were covered with a non-resorbable (expanded polytetrafluoroethylene
      [ePTFE]) membrane to exclude soft tissues. Animals were sacrificed either 4 or 12
      weeks later. Histomorphometric analysis included the percentage of new bone
      contact with the implant, the area of new bone, and the percentage of defect
      fill. This article describes results with the PLGA carrier. RESULTS: All implants
      demonstrated clinical and radiographic success with the amount of new bone formed
      dependent on the time and presence/absence of rhBMP-2 and presence/absence of a
      membrane. The percentage of bone-to-implant contact was greater with rhBMP-2, and
      after 12 weeks of healing, there was approximately one-third of the implant
      contacting bone in the defect site. After 4 weeks, the presence of a membrane
      appeared to slow new bone area formation. The percentage of fill in membrane
      treated sites with rhBMP-2 rose from 24% fill to 42% after 4 and 12 weeks,
      respectively. Without rhBMP-2, the percentage of fill was 14% rising to 36% fill,
      respectively. CONCLUSIONS: After 4 weeks, the rhBMP-2-treated sites had a
      significantly higher percentage of contact, more new bone area, and higher
      percentage of defect fill than the sites without rhBMP-2. After 12 weeks, there
      was no significant difference in sites with or without rhBMP-2 regarding
      percentage of contact, new bone area, or percentage of defect fill. In regard to
      these three outcomes, comparing the results with this carrier to the results
      reported earlier with a collagen carrier in this study, only the area of new bone
      was significantly different with the collagen carrier resulting in greater bone
      than the PLGA carrier. Thus, the PLGA carrier for rhBMP-2 significantly
      stimulated bone formation around dental implants in this model after 1 month but
      not after 3 months of healing. The use of this growth factor and carrier
      combination appears to stimulate early bone healing events around the implants
      but not quite to the same degree as a collagen carrier.

PMID- 16805682
TI  - Interaction of chlorhexidine with smooth and rough types of titanium surfaces.
AB  - BACKGROUND: Chlorhexidine (CHX) digluconate exerts plaque inhibitory efficacy in
      the natural dentition environment due to a superior degree of persistence at the
      tooth surface. The purpose of the present study was to assess the interaction of
      CHX with titanium surfaces to estimate its antiplaque potential in the peri
      implant environment. METHODS: Saliva-coated machined smooth (S) and sand-blasted
      acid-etched rough (R) titanium disks were soaked in either 0.1% or 0.2% CHX
      solution. After 24 hours, CHX amounts that were adsorbed, washed out, and
      desorbed from the titanium surfaces were determined spectrophotometrically at 230
      nm. The antibacterial activity of CHX-treated titanium disks was assessed by
      measuring bacterial inhibition zones on Streptococcus mutans lawns. RESULTS:
      Titanium disks adsorbed 3% to 8% of the available CHX, which was significantly
      higher with 0.2% CHX (P<0.001) than with 0.1% CHX and two-fold higher on the R
      titanium disks compared to S titanium surface (P<0.001). After rinsing with
      water, 2.2% of the adsorbed CHX was washed out. Over 24 hours, S- and R-type
      disks released 1.1% and 0.6% of the adsorbed agent, respectively. Larger
      bacterial inhibition zones were obtained with 0.2% CHX and in R disks compared to
      S disks. CONCLUSIONS: CHX displayed persistence at the titanium surface. The
      adsorption level and bacterial growth inhibition were affected by CHX
      concentration and titanium surface characteristics, with higher levels of
      adsorption and antibacterial activity with 0.2% CHX and rough titanium surface.
      The slow CHX release rate suggests persistence of this agent at the titanium
      pellicle surface, which can provide a long-term antiplaque effect.

PMID- 16805683
TI  - Host response to titanium dental implant placement evaluated in a human oral
      model.
AB  - BACKGROUND: Recent reports have questioned if metal sensitivity may arise from
      exposure to titanium. The objective of this study was to histologically evaluate
      non-perforated mucosa covering submerged maxillary titanium implants with regard
      to induced tissue reactions. METHODS: Thirteen patients, 21 to 69 years of age,
      without previous implants were included. After initial examination, the bone
      crest areas destined for dental implant placement were exposed, and threaded
      external hex dental implants were inserted. Prior to wound closure, a full
      mucosal tissue slice was biopsied from the edge of the mucoperiosteal flap
      (baseline). The patients were monitored monthly for 6 months. At the abutment
      connection, biopsies were taken by a 6-mm punch, altogether yielding 26
      specimens. Tissue reactions were analyzed by coded histometric analysis at four
      defined areas at increasing distance from the oral epithelium, including ratios
      of inflammatory cells (IC)/epithelial cells, IC/fibroblasts, and number of dense
      particles. RESULTS: The stained sections portrayed gingival tissue with intact
      oral epithelium and connective tissue with variable accumulation of IC.
      Experimental biopsies demonstrated mineralized areas and dense particles of
      different sizes. Analysis of variance revealed a higher IC/fibroblast ratio for
      level 3 at baseline compared to level 3 at 6 months (P<0.01). Furthermore, a
      significant decrease in IC/fibroblast ratio was observed between levels 2 and 3
      and 2 and 4 at 6 months (P<0.001). The connective tissue level facing the cover
      screw contained the highest number of dense particles (P<0.01). CONCLUSIONS:
      Tissue sensitivity reactions to titanium implants were not disclosed. All 6-month
      biopsies contained dense particles that were most likely metals.

PMID- 16805684
TI  - Comparative analysis of the effects of a novel vacuolar adenosine 5'
      triphosphatase inhibitor, FR202126, and doxycycline on bone loss caused by
      experimental periodontitis in rats.
AB  - BACKGROUND: Doxycycline is reported to inhibit alveolar bone destruction by
      blocking matrix metalloproteinases (MMPs). Nevertheless, MMPs are not involved in
      osteoclastic bone resorption; osteoclasts directly resorb bone. An acidic
      microenvironment, which is formed by vacuolar adenosine 5'-triphosphatase (V
      ATPase) expressed in the plasma membranes of osteoclasts, is indispensable for
      osteoclastic bone resorption. In the present study, we investigated the potential
      role of the acidic environment on periodontal bone destruction using a novel and
      specific V-ATPase inhibitor, FR202126, which we compared to doxycycline. METHODS:
      Inhibitory activity against in vitro bone resorption was examined by measuring
      the Ca2+ release from murine calvariae cultured for 6 days, which were treated
      with interleukin-1 (IL-1), IL-6, or parathyroid hormone. Experimental
      periodontitis was induced by a ligature wire tied around the contact between the
      first and second maxillary molars of male Wistar rats. FR202126 and doxycycline
      were administered orally once daily for 6 days. Seven days after tying, the
      maxillae were dissected and mesiodistal longitudinal paraffin sections, including
      interdental alveolar bone, were processed for histopathologic analysis. RESULTS:
      FR202126 inhibited bone resorption almost completely in calvaria cultures induced
      by three stimulators, whereas doxycycline was unable to prevent in vitro bone
      resorption. Oral administration of FR202126 significantly prevented alveolar bone
      loss in experimental periodontitis. However, doxycycline did not inhibit alveolar
      bone destruction. CONCLUSION: These results suggest that an acidic
      microenvironment plays a more important role than MMPs in periodontal alveolar
      bone destruction and that V-ATPase inhibitors may offer a new approach to the
      treatment of periodontal disease.

PMID- 16805685
TI  - Effects of Er:YAG laser and ultrasonic treatment on fibroblast attachment to root
      surfaces: an in vitro study.
AB  - BACKGROUND: The aim of this study was to analyze the effects of erbium
      doped:yttrium, aluminum, and garnet (Er:YAG) laser and ultrasonic treatment on
      fibroblast attachment to periodontally diseased root surfaces. METHODS: Thirty
      single-rooted human periodontally involved teeth were included in this study. A
      total of 60 specimens were obtained from all selected teeth and were randomly
      assigned to the following three groups: group A, untreated control group; group
      B, ultrasonic group; and group C, Er:YAG laser at 160 mJ/pulse at 10 Hz group.
      All of the specimens were incubated in petri dishes with fibroblast suspension
      and observed by scanning electron microscopy. RESULTS: Laser-treated specimens
      showed a significantly higher cell density number, with a mean+/-SD of 3,720+/
      316 cells/mm2. The ultrasonically treated group showed a lower cell density
      number, with a mean+/-SD of 658+/-140 cells/mm2. The untreated control group
      showed the lowest cell density number, with a mean+/-SD of 130+/-80 cells/mm2.
      Differences between all groups were significant (P<0.0001). CONCLUSION: The
      results of the study indicate that untreated control surfaces and ultrasonically
      treated surfaces exhibited a significantly lower number of attached cells
      compared to laser-treated specimens, which showed a significantly higher cell
      density number.

PMID- 16805686
TI  - Osteoprotegerin and receptor activator of nuclear factor-kappa B ligand
      modulation by enamel matrix derivative in human alveolar osteoblasts.
AB  - BACKGROUND: Bone regeneration techniques increasingly rely on the use of
      exogenous molecules able to enhance tissue formation in pathologic and traumatic
      defects. An enamel matrix derivative (EMD) has been largely used to promote tooth
      ligament regeneration within periodontal pockets. Recent evidence suggests that
      EMD may contribute to inducing osteoblast growth and differentiation. We
      investigated the effects of EMD on growth and osteogenic marker modulation in
      human mandibular osteoblasts. METHODS: We focused our attention on cell growth by
      3-(4,5-dimethyl[thiazol-2-yl]-3,5-diphery)tetradium bromide (MTT) assay, cell
      differentiation, mineralized nodule formation, and, in particular, the expression
      of receptor activator of nuclear factor-kappa B ligand (RANKL), the main
      osteoclast differentiation factor, and its decoy receptor, osteoprotegerin (OPG),
      by enzyme-linked immunosorbent assay. RESULTS: Cell growth was significantly
      increased by EMD. Similarly, a significantly higher quantity of OPG and a lower
      amount of RANKL were detectable in groups treated with 50 and 100 microg/ml at
      weeks 1, 2, and 3, and alkaline phosphatase activity and osteocalcin production
      were enhanced in cultures treated with 50 and 100 microg/ml at weeks 2 and 3.
      Mineralized nodules appeared bigger and more numerous in cultures treated with 50
      and 100 microg/ml EMD. CONCLUSIONS: EMD was able to enhance osteoblast cell
      growth and the expression of markers of osteoblastic phenotype and
      differentiation. EMD also seemed able to create a favorable osteogenic
      microenvironment by reducing RANKL release and enhancing osteoblastic OPG
      production.

PMID- 16805687
TI  - Gingival squamous cell carcinoma: diagnostic delay or rapid invasion?
AB  - BACKGROUND: The similarity between gingival squamous cell carcinoma (GSCC) and
      more common periodontal lesions may lead to a delay in diagnosis or misdiagnosis.
      Neoplastic lesions of gingival tissues are frequently diagnosed at an advanced
      stage. METHODS: To assess the relative time from when patients first become aware
      of the problem to histopathologic diagnosis (total diagnostic time), 59
      consecutive oral cancer cases were examined in this study. The following
      variables were considered: age, gender, smoking habits, tumor stage at diagnosis,
      and total diagnostic time. The median of the patients' total diagnostic time (1.5
      months) was used as a cutoff point to distinguish between delayed and non-delayed
      cases. Analysis of the variables was undertaken using the Student t test and chi2
      test, with a 95% confidence interval (CI). RESULTS: The total diagnostic time was
      <1.5 months for 75% of gingival carcinomas, 50% of tongue carcinomas, and 78% of
      floor-of-the-mouth carcinomas. It was >1.5 months for 25% of gingival carcinomas,
      50% of tongue carcinomas, and 21% of floor-of-the-mouth carcinomas. No
      significant differences in time before diagnosis were found when gingival cancers
      were compared to other oral tumors (chi2=0.21; 95% CI=-0.40 to 0.26). However, by
      the time of diagnosis, gingival cancers had invaded adjacent structures more
      frequently than other oral cancers (chi2=13.51; 95% CI=0.18 to 0.85).
      CONCLUSIONS: The gingival location of oral squamous cell carcinoma (OSCC) was
      associated with advanced stages at the time of diagnosis, due to early invasion
      of contiguous bone tissue (T4-primary tumor). This would indicate that even
      earlier referral and diagnosis are necessary.

PMID- 16805688
TI  - Digital volume tomography in the diagnosis of peri-implant defects: an in vitro
      study on native pig mandibles.
AB  - BACKGROUND: The aim of this study of native pig mandibles was to investigate the
      accuracy and quality of the representation of peri-implant defects by intraoral
      radiography (IR), panoramic radiography (PR), computer tomography (CT), and
      digital volume tomography (DVT). METHODS: The examination was carried out on 19
      native pig mandibles. In the toothless sections of the mandibles, one or two
      implants were inserted. Following the standardized preparation of peri-implant
      defects (11 each of dehiscences, fenestrations, and 2- to 3-walled intrabony
      defects), IR, PR, CT, and DVT were performed. The peri-implant defects were
      measured using appropriate software on the digitized IR and PR image programs. As
      a control method, the peri-implant bone defects were measured directly using a
      reflecting stereomicroscope with measuring ocular. The statistical comparison
      between the measurements of the radiographic scans and those of the direct
      readings of the peri-implant defects was performed with Pearson's correlation
      coefficient. The quality of the radiographic scans was determined through the
      subjective perception and detectability of the peri-implant defects by five
      independent observers. RESULTS: In the DVT and CT scans, it was possible to
      measure all the bone defects in three planes. Comparison with the direct peri
      implant defect measurements yielded a mean deviation of 0.17+/-0.11 mm for the
      DVT scans and 0.18+/-0.12 mm for the CT scans. On the IR and PR images, the
      defects could be detected only in the mesio-distal and cranio-caudal planes. In
      comparison with the direct measurements of the peri-implant defects, the IR
      images revealed a mean deviation of 0.34+/-0.30 mm, and the PR images revealed a
      mean deviation of 0.41+/-0.35 mm. The quality rating of the radiographic images
      was highest for the DVT scans. CONCLUSIONS: Overall, the CT and DVT scans
      displayed only a slight deviation in the extent of the peri-implant defects. Both
      radiographic imaging techniques permitted imaging of peri-implant defects in
      three planes, true to scale, and without overlay or distortion. The DVT scans
      showed the best imaging quality.

PMID- 16805689
TI  - Human periodontal fibroblast response to enamel matrix derivative, amelogenin,
      and platelet-derived growth factor-BB.
AB  - BACKGROUND: The ideal goal of clinical therapy in periodontal defects is
      regeneration of all lost structures. For regeneration to occur, cell
      proliferation, migration, and extracellular matrix synthesis are prerequisites.
      Attempts at regeneration of periodontal defects by guided tissue regeneration
      using bone grafts and membranes have not always yielded predictable results.
      Recently, attempts at engineering the defects using various materials have shown
      promising results. Two such approaches have been used to regenerate periodontal
      defects, one using extracellular matrix such as enamel matrix proteins and the
      other using growth factors. However, to our knowledge, no study has looked at
      combining these two approaches to achieve potentially even greater regeneration.
      METHODS: Primary human periodontal ligament (PDL) fibroblasts were explanted, and
      alkaline phosphatase (ALK PHOS) activity was determined. Phenotypically different
      cell lines were incubated for 1, 3, 6, and 10 days in 0.2% fetal bovine serum
      (FBS) media containing different concentrations of either enamel matrix
      derivative (EMD), amelogenin, platelet-derived growth factor-BB (PDGF-BB),
      EMD+PDGF-BB, or amelogenin+PDGF-BB. A culture of 0.2% FBS alone served as a
      negative control, and a culture of 10% FBS served as a positive control. Cell
      proliferation was measured using a Coulter counter to determine the cell number.
      The effects on a wound-fill model were evaluated by scraping a 3-mm wide cell
      free zone in PDL monolayers across the diameter of the tissue-culture plate and
      determining PDL cell migration into the cell-free zone using computer assisted
      histomorphometry. RESULTS: Compared to the control, only EMD+PDGF-BB
      significantly increased PDL cell proliferation in an ALK PHOS (-) cell line
      (P<0.001), and EMD alone, EMD+PDGF-BB, and amelogenin+PDGF-BB significantly
      increased PDL cell proliferation in an ALK PHOS (+) cell line (P<0.001) with
      EMD+PDGF-BB showing a trend for greater proliferation than either PDGF or EMD
      alone. Individually, EMD and amelogenin had no significant effect on PDL cell
      proliferation. In the wound-fill experiment, all factors and their combinations
      except amelogenin significantly enhanced cell migration compared to the control
      (P<0.05) at the wound edge. In addition, EMD+PDGF-BB had additive effects on the
      ALK PHOS (-) cell line at the wound edge. At the center of the wound, neither EMD
      nor amelogenin had a significant wound-fill effect. However, the combination of
      EMD+PDGF-BB additively increased wound fill for both ALK PHOS (+) and ALK PHOS (
      ) cells. CONCLUSIONS: The combination of EMD and PDGF-BB produces greater
      proliferative and wound-fill effects on PDL cells than each by themselves. If
      these combined effects can be translated clinically, one may see greater
      regeneration in periodontal defects with this combination. However, amelogenin
      does not have significant effects on PDL cell proliferation or migration by
      itself. This may suggest that either another enamel matrix component in EMD may
      be responsible for some of its clinical effects, or that amelogenin alone may not
      trigger the regenerative potential of periodontal tissues and that it requires a
      combined interaction with other enamel matrix components of EMD to direct the
      regenerative process.

PMID- 16805690
TI  - Surgical versus non-surgical periodontal treatment: psychosocial factors and
      treatment outcomes.
AB  - BACKGROUND: This research explored how patients with surgical versus non-surgical
      periodontal treatment differ in trait anxiety, depression, perceived stress, and
      well-being on the day of surgery and in their reported pain and use of pain
      medication 2 and 4 weeks after treatment. In addition, it was investigated how
      psychosocial factors affected reported pain, use of pain medication, and wound
      healing. METHODS: Data were collected from 70 dental patients (34 males and 36
      females; average age: 54.79 years; SD=13.206) on the day of their periodontal
      treatment and 2 and 4 weeks after this treatment. The psychosocial factors (i.e.,
      trait anxiety, depression, perceived stress, and well-being) were measured with
      standardized scales. The patients' providers assessed their wound healing 2 weeks
      after treatment. RESULTS: On the day of treatment, non-surgical patients had
      higher anxiety, depression, and stress, and poorer well-being than surgical
      patients. However, surgical patients reported a higher level of pain during the
      second week, and greater consumption of analgesics during the second and fourth
      week. Anxiety, depression, stress, and well-being correlated with the reported
      level of pain, the use of pain medication, and wound healing after periodontal
      treatment. CONCLUSIONS: Psychosocial factors (i.e., anxiety, depression, stress,
      and well-being) can affect the patients' quality of life on the day of
      periodontal treatment and the pain experience and medications used after surgical
      and non-surgical periodontal therapy (4-week period). Patient-provider
      communication should address the role of these factors in the treatment process.

PMID- 16805691
TI  - Accuracy of cone beam computed tomography for periodontal defect measurements.
AB  - BACKGROUND: Periodontal diagnosis relies heavily on traditional two-dimensional
      radiographic assessment. Despite efforts in improving reliability, current
      methods of detecting bone level changes over time or determining three
      dimensional architecture of osseous defects are inadequate. To address these
      issues, computed tomography (CT) has been explored because of its ability to
      produce accurate three-dimensional imaging, but limitations such as radiation,
      machine size, and cost have made this approach impractical. Recently, cone beam
      computed tomography (CBCT) has turned this concept into potential reality because
      these lower-cost small machines produce high-quality data. Yet there is little
      research to establish periodontal bone measurement using CBCT as a valid method.
      Therefore, the aim of this study was to compare CBCT measurements of periodontal
      defects to traditional methods. METHODS: Artificial osseous defects were created
      on mandibles of dry skulls. CBCT scanning, periapical radiography (PA), and
      direct measurements using a periodontal probe were compared to an electronic
      caliper that was used as a standard reference. RESULTS: Linear measurements for
      all defects revealed no statistical differences between bone sounding,
      radiography, and CBCT. There was a significant difference when comparing isolated
      interproximal measurements using a probe versus the caliper (P<0.001) but no
      significant difference for CBCT or radiography. All bony defects were
      identifiable and measurable directly or with CBCT. In comparison, buccal and
      lingual defects could not be measured with radiographs. CONCLUSIONS: Overall, all
      three modalities are useful for identifying interproximal periodontal defects.
      Compared to radiographs, the three-dimensional capability of CBCT offers a
      significant advantage because all defects can be detected and quantified.

PMID- 16805692
TI  - A histologic evaluation of various stages of palatal healing following
      subepithelial connective tissue grafting procedures: a comparison of eight cases.
AB  - BACKGROUND: It is often necessary to procure tissue from the same area of the
      palate in cases where connective autogenous grafting procedures are warranted due
      to limitations caused by anatomical features. The purpose of this study was to
      determine whether the length of time between a first procurement and a second
      would have any bearing on the quality of tissue available for recipient sites.
      METHODS: Eight patients requiring more than one grafting procedure underwent
      surgery at baseline and again at various intervals ranging from 6 weeks to 11
      months. Specimens were taken from the palate and evaluated microscopically, and
      photographs were taken for purposes of visual comparison. RESULTS: The 6.9- to
      7.7-week specimens exhibited complete reepithelialization. The lamina propriae
      were composed of a cellular proliferation of fibroblasts with loosely arranged
      collagen deposition and an occasional thin vascular channel. However, remodeling
      of the wound appeared complete in the specimens removed at the 9-week interval
      and beyond. The lamina propria was, in general, composed of thick, dense,
      interlacing bundles of collagen. Small-caliber blood vessels were interspersed
      throughout the fibrous element. CONCLUSION: Reharvesting of tissue performed
      earlier than at 9 weeks may result in poorer autogenous graft quality due to
      indications that remodeling of the connective tissue is still progressing and not
      as mature as specimens noted at weeks 9 to 47.

PMID- 16805693
TI  - Modified semilunar coronally advanced flap.
AB  - BACKGROUND: Correction of mucogingival recession deformities with a variety of
      periodontal plastic surgery procedures has been described, each demonstrating a
      variable degree of success. A modified semilunar coronally advanced flap is
      described for the treatment of recession defects on multiple adjacent teeth.
      METHODS: Semilunar incisions were made apical to the recession defects, starting
      within mucosa and extended mesio-distally, arching more coronally to terminate
      apical to the papillae mesial and distal to the teeth exhibiting the defects. The
      papilla between the teeth with recession was coronally advanced after a split
      thickness dissection and sutured more coronally, over the deepithelialized
      portion of the original papilla. The flap design gave better mobility and
      stability to the repositioned pedicle than previously described semilunar
      coronally advanced flap procedures. RESULTS: Seven cases treated with this
      approach healed without complication and remained stable throughout the 8 to 22
      months of post-surgical observation. CONCLUSIONS: This technique will be
      particularly valuable when previous attempts for root coverage with soft tissue
      autografts have resulted in residual recession defects on adjacent teeth and in a
      thicker-tissue biotype that would be amenable to partial-thickness dissection. An
      adequate thickness of tissue that will allow a partial-thickness flap dissection
      is required to avoid tooth or alveolar bone fenestrations. This technique
      provides better control over flap repositioning than previously described
      semilunar coronally advanced flaps.

PMID- 16805694
TI  - Anorganic bovine matrix/p-15 "flow" in the treatment of periodontal defects: case
      series with 12 months of follow-up.
AB  - BACKGROUND: Nowadays there is a trend in developing biologic modalities that may
      enhance wound healing of specific sites. In this regard, a cell-binding activity
      of type I collagen provided by a synthetic peptide (P-15) was incorporated in a
      scaffold (anorganic bovine matrix [ABM]) to facilitate the attachment, migration,
      and differentiation of cells. This case series describes a surgical protocol for
      the placement of ABM/P-15 "flow" during regenerative procedures. METHODS: Wide
      periodontal defects were treated with sulcular incisions preserving the papillae,
      full-thickness flap reflection, granulation tissue debridement, mechanical and
      chemical root surface treatment, placement of the ABM/P-15 "flow," and wound
      closure sutures. Weekly, and then monthly, deplaquing was performed until the 12
      month postoperative recall, in which the clinical parameters were reevaluated.
      RESULTS: Significant clinical changes, including probing depth reduction and
      relative clinical attachment level gain, were achieved after the 12-month period.
      The radiographs demonstrated increase in radiopacity when compared to those taken
      initially, suggesting hard tissue improvements. CONCLUSIONS: The topography of
      the defects described here could be understood as a challenge for regeneration,
      once the previous breakdown of the supporting tissues had diminished the source
      of cells for the healing process and reduced the number of residual walls to
      retain the graft material. Thus, it seems that the ABM/P-15 "flow" contributed to
      the clinical success achieved. Based on this result, ABM/P-15 "flow" could be a
      useful and beneficial material for the treatment of periodontal defects.

PMID- 16805695
TI  - Astrobiology influx to astrobiology in flux.

PMID- 16805696
TI  - Bacterial community in ancient Siberian permafrost as characterized by culture
      and culture-independent methods.
AB  - The microbial composition of ancient permafrost sediments from the Kolyma lowland
      of Northeast Eurasia was examined through culture and culture-independent
      approaches. These sediments have been continuously frozen for 5,000 to 2-3
      million years. A total of 265 Bacteria 16S rRNA gene sequences were amplified
      from the permafrost total-community genomic DNA and screened by amplified
      ribosomal 16S rRNA restriction analysis. Members of three major lineages were
      found: gamma-Proteobacteria (mostly Xanthomonadaceae), Actinobacteria, and
      Firmicutes. We also determined partial 16S rRNA gene sequences of 49 isolates
      from a collection of 462 aerobes isolated from these sediments. The bacteria
      included Actinomycetales (Arthrobacter and Microbacteriaceae); followed by the
      Firmicutes (Exiguobacterium and Planomicrobium); the Bacteroidetes
      (Flavobacterium); the gamma-Proteobacteria (Psychrobacter); and the alpha
      Proteobacteria (Sphingomonas). Both culture and culture-independent approaches
      showed the presence of high and low G+C Gram-positive bacteria and gamma
      Proteobacteria. Some of the 16S rRNA gene sequences of environmental clones
      matched those of Arthrobacter isolates. Two-thirds of the isolates grew at -2.5
      degrees C, indicating that they are psychroactive, and all are closely related to
      phylogenetic groups with strains from other cold environments, mostly commonly
      from Antarctica. The culturable and non-culturable microorganisms found in the
      terrestrial permafrost provide a prototype for possible life on the cryogenic
      planets of the Solar System.

PMID- 16805697
TI  - Endolithic cyanobacteria in halite rocks from the hyperarid core of the Atacama
      Desert.
AB  - In the driest parts of the Atacama Desert there are no visible life forms on soil
      or rock surfaces. The soil in this region contains only minute traces of bacteria
      distributed in patches, and conditions are too dry for cyanobacteria that live
      under translucent stones. Here we show that halite evaporite rocks from the
      driest part of the Atacama Desert are colonized by cyanobacteria. This
      colonization takes place just a few millimeters beneath the rock surface,
      occupying spaces among salt crystals. Our work reveals that these communities are
      composed of extremely resistant Chroococcidiopsis morphospecies of cyanobacteria
      and associated heterotrophic bacteria. This newly discovered endolithic
      environment is an extremely dry and, at the same time, saline microbial habitat.
      Photosynthetic microorganisms within dry evaporite rocks could be an important
      and previously unrecognized target for the search for life within our Solar
      System.

PMID- 16805698
TI  - Magnetism, iron minerals, and life on Mars.
AB  - A short critical review is provided on two questions linking magnetism and
      possible early life on Mars: (1) Did Mars have an Earth-like internal magnetic
      field, and, if so, during which period and was it a requisite for life? (2) Is
      there a connection between iron minerals in the martian regolith and life? We
      also discuss the possible astrobiological implications of magnetic measurements
      at the surface of Mars using two proposed instruments. A magnetic remanence
      device based on magnetic field measurements can be used to identify Noachian age
      rocks and lightning impacts. A contact magnetic susceptibility probe can be used
      to investigate weathering rinds on martian rocks and identify meteorites among
      the small regolith rocks. Both materials are considered possible specific niches
      for microorganisms and, thus, potential astrobiological targets. Experimental
      results on analogues are presented to support the suitability of such in situ
      measurements.

PMID- 16805699
TI  - Space physics, Mars, and life.

PMID- 16805700
TI  - Oxidant enhancement in martian dust devils and storms: implications for life and
      habitability.
AB  - We investigate a new mechanism for producing oxidants, especially hydrogen
      peroxide (H2O2), on Mars. Large-scale electrostatic fields generated by charged
      sand and dust in the martian dust devils and storms, as well as during normal
      saltation, can induce chemical changes near and above the surface of Mars. The
      most dramatic effect is found in the production of H2O2 whose atmospheric
      abundance in the "vapor" phase can exceed 200 times that produced by
      photochemistry alone. With large electric fields, H2O2 abundance gets large
      enough for condensation to occur, followed by precipitation out of the
      atmosphere. Large quantities of H2O2 would then be adsorbed into the regolith,
      either as solid H2O2 "dust" or as re-evaporated vapor if the solid does not
      survive as it diffuses from its production region close to the surface. We
      suggest that this H2O2, or another superoxide processed from it in the surface,
      may be responsible for scavenging organic material from Mars. The presence of
      H2O2 in the surface could also accelerate the loss of methane from the
      atmosphere, thus requiring a larger source for maintaining a steady-state
      abundance of methane on Mars. The surface oxidants, together with storm electric
      fields and the harmful ultraviolet radiation that readily passes through the thin
      martian atmosphere, are likely to render the surface of Mars inhospitable to life
      as we know it.

PMID- 16805701
TI  - Oxidant enhancement in martian dust devils and storms: storm electric fields and
      electron dissociative attachment.
AB  - Laboratory studies, numerical simulations, and desert field tests indicate that
      aeolian dust transport can generate atmospheric electricity via contact
      electrification or "triboelectricity." In convective structures such as dust
      devils and dust storms, grain stratification leads to macroscopic charge
      separations and gives rise to an overall electric dipole moment in the aeolian
      feature, similar in nature to the dipolar electric field generated in terrestrial
      thunderstorms. Previous numerical simulations indicate that these storm electric
      fields on Mars can approach the ambient breakdown field strength of approximately
      25 kV/m. In terrestrial dust phenomena, potentials ranging from approximately 20
      to 160 kV/m have been directly measured. The large electrostatic fields predicted
      in martian dust devils and storms can energize electrons in the low pressure
      martian atmosphere to values exceeding the electron dissociative attachment
      energy of both CO2 and H2O, which results in the formation of the new chemical
      products CO/O- and OH/H-, respectively. Using a collisional plasma physics model,
      we present calculations of the CO/O- and OH/H- reaction and production rates. We
      demonstrate that these rates vary geometrically with the ambient electric field,
      with substantial production of dissociative products when fields approach the
      breakdown value of approximately 25 kV/m. The dissociation of H2O into OH/H-
      provides a key ingredient for the generation of oxidants; thus electrically
      charged dust may significantly impact the habitability of Mars.

PMID- 16805703
TI  - Infrared spectra and radiation stability of H2O2 ices relevant to Europa.
AB  - In this paper we present spectra of H2O2-containing ices in the near- and mid
      infrared (IR) regions. Spectral changes on warming are shown, as is a comparison
      of near-IR bands of H2O and H2O2-containing ices. An estimate of the A-value
      (absolute intensity) for the largest near- IR feature of H2O2 is given. Radiation
      decay half-lives are reported for 19 K and 80 K, and are related to the surface
      radiation doses on Europa. The radiation data show that H2O2 destruction is
      slower at 80 K than 19 K, and are consistent with the claim that icy material in
      the outermost micrometer of Europa's surface has been heavily processed by
      radiation.

PMID- 16805702
TI  - Clathrate hydrates of oxidants in the ice shell of Europa.
AB  - Europa's icy surface is radiolytically modified by high-energy electrons and
      ions, and photolytically modified by solar ultraviolet photons. Observations from
      the Galileo Near Infrared Mapping Spectrometer, ground-based telescopes, the
      International Ultraviolet Explorer, and the Hubble Space Telescope, along with
      laboratory experiment results, indicate that the production of oxidants, such as
      H2O2, O2, CO2, and SO2, is a consequence of the surface radiolytic chemistry.
      Once created, some of the products may be entrained deeper into the ice shell
      through impact gardening or other resurfacing processes. The temperature and
      pressure environments of regions within the europan hydrosphere are expected to
      permit the formation of mixed clathrate compounds. The formation of carbon
      dioxide and sulfur dioxide clathrates has been examined in some detail. Here we
      add to this analysis by considering oxidants produced radiolytically on the
      surface of Europa. Our results indicate that the bulk ice shell could have a
      approximately 1.7-7.6% by number contamination of oxidants resulting from
      radiolysis at the surface. Oxidant-hosting clathrates would consequently make up
      approximately 12-53% of the ice shell by number relative to ice, if oxidants were
      entrained throughout. We examine, in brief, the consequences of such
      contamination on bulk ice shell thickness and find that clathrate formation could
      lead to substantially thinner ice shells on Europa than otherwise expected.
      Finally, we propose that double occupancy of clathrate cages by O2 molecules
      could serve as an explanation for the observation of condensed-phase O2 on
      Europa. Clathrate-sealed, gas-filled bubbles in the near surface ice could also
      provide an effective trapping mechanism, though they cannot explain the 5771 A
      (O2)2 absorption.

PMID- 16805704
TI  - Experimentally tracing the key steps in the origin of life: The aromatic world.
AB  - Life is generally believed to emerge on Earth, to be at least functionally
      similar to life as we know it today, and to be much simpler than modern life.
      Although minimal life is notoriously difficult to define, a molecular system can
      be considered alive if it turns resources into building blocks, replicates, and
      evolves. Primitive life may have consisted of a compartmentalized genetic system
      coupled with an energy-harvesting mechanism. How prebiotic building blocks self
      assemble and transform themselves into a minimal living system can be broken into
      two questions: (1) How can prebiotic building blocks form containers, metabolic
      networks, and informational polymers? (2) How can these three components
      cooperatively organize to form a protocell that satisfies the minimal
      requirements for a living system? The functional integration of these components
      is a difficult puzzle that requires cooperation among all the aspects of
      protocell assembly: starting material, reaction mechanisms, thermodynamics, and
      the integration of the inheritance, metabolism, and container functionalities.
      Protocells may have been self-assembled from components different from those used
      in modern biochemistry. We propose that assemblies based on aromatic hydrocarbons
      may have been the most abundant flexible and stable organic materials on the
      primitive Earth and discuss their possible integration into a minimal life form.
      In this paper we attempt to combine current knowledge of the composition of
      prebiotic organic material of extraterrestrial and terrestrial origin, and put
      these in the context of possible prebiotic scenarios. We also describe laboratory
      experiments that might help clarify the transition from nonliving to living
      matter using aromatic material. This paper presents an interdisciplinary approach
      to interface state of the art knowledge in astrochemistry, prebiotic chemistry,
      and artificial life research.

PMID- 16805705
TI  - Cellular repair strategies for spinal cord injury.
AB  - The implantation of exogenous cells or tissues has been a popular and successful
      strategy to overcome physical discontinuity and support axon growth in
      experimental models of spinal cord injury (SCI). Cellular therapies exhibit a
      multifarious potential for SCI restoration, providing not only a supportive
      substrate upon which axons can traverse the injury site, but also reducing
      progressive tissue damage and scarring, facilitating remyelination repair, and
      acting as a source for replacing and re-establishing lost neural tissue and its
      circuitry. The past two decades of research into cell therapies for SCI repair
      have seen the progressive evolution from whole tissue strategies, such as
      peripheral nerve grafts, to the use of specific, purified cell types from a
      diverse range of sources and, recently, to the employment of stem or neural
      precursor cell populations that have the potential to form a full complement of
      neural cell types. Although the progression of cell therapies from laboratory to
      clinical implementation has been slow, human SCI safety and efficacy trials
      involving several cell types within the US appear to be close at hand.

PMID- 16805706
TI  - Epigenetic conversion of human adult bone mesodermal stromal cells into
      neuroectodermal cell types for replacement therapy of neurodegenerative
      disorders.
AB  - Tissue-specific stem cells, such as bone marrow-derived mesodermal stromal cells
      (MSCs), are thought to be lineage restricted and, therefore, could only be
      differentiated into cell types of the tissue of origin. Several recent studies,
      however, suggest that these types of stem cells might be able to break barriers
      of germ layer commitment and differentiate in vitro and/or in vivo into cells of
      different tissues, such as neuroectodermal cell types. Recently, protocols for
      high-yield generation of undifferentiated neural stem cell (NSC)-like cells from
      MSCs of primate and human origin were reported. Undifferentiated NSCs are
      commonly used and are more suitable for neurotransplantation compared with fully
      differentiated neural cells, as differentiated neural cells are well known to
      poorly survive detachment and subsequent transplantation procedures. These human
      MSC-derived NSC-like cells (MSC-NSCs) grow in neurosphere-like structures and
      express high levels of early neuroectodermal markers, but lose characteristics of
      MSCs. In the presence of selected growth factors, human MSC-NSCs can be
      differentiated into the three main neural phenotypes: astroglia, oligodendroglia
      and neurons. Compared with direct differentiation of human MSCs into mature
      neural cells, the conversion step seems to be essential to generate mature
      functional neuroectodermal cells. This review describes the techniques for the
      conversion of human MSCs into NSCs and summarises the data on epigenetic
      conversion of human MSCs into immature neuroectodermal cells. These cells provide
      a powerful tool for investigating the molecular mechanisms of neural
      differentiation, and might serve as an autologous cell source to treat acute and
      chronic neurodegenerative diseases.

PMID- 16805707
TI  - The tumour microenvironment and implications for cancer immunotherapy.
AB  - Tumour cells exist in a complex milieu of cellular and non-cellular components
      comprising fibroblasts, endothelial cells, immune cells and metabolites of
      cellular respiration. An elaborate interplay between these components and tumour
      cells exists with implications for immunological recognition of tumour cells.
      Tumours have been shown to alter their antigen and cytokine profiles, desensitise
      and impair immune defences, signal fibroblasts to facilitate metastasis, and take
      advantage of acidic and hypoxic conditions that impede normal cells. This paper
      aims to review the roles of the stroma, extracellular matrix and chemistry of the
      microenvironment on tumour growth, with particular emphasis on interactions with
      the immune system, and to highlight some of the novel therapeutic strategies that
      target the tumour microenvironment.

PMID- 16805708
TI  - Pertussis immunisation in adolescents and adults--Bordetella pertussis
      epidemiology should guide vaccination recommendations.
AB  - Pertussis, or whooping cough, is an infectious disease that is caused by
      Bordetella pertussis, affects all age groups and is vaccine preventable.
      Recently, an increase in reported cases of pertussis in adolescents and adults
      has been noted in many countries despite high immunisation rates in children.
      Today pertussis outnumbers all other paediatric vaccine-preventable diseases in
      some countries. This observation can best be explained by an increased awareness
      of the disease, the availability of new diagnostic tests and, perhaps, suboptimal
      efficacy of some pertussis vaccines. In general, B. pertussis infections in
      adolescents and adults are of concern as they are the most important source of
      transmission of B. pertussis infections to young, unprotected infants. Many
      studies with diphtheria and tetanus toxoid, acellular pertussis component
      combination vaccines, specifically designed for use in adolescents and adults,
      have been performed and excellent tolerability and immunogenicity have been
      demonstrated. With the availability of two such products, booster doses in
      adolescents have been introduced in Canada, Austria, Australia, France, Germany
      and the US, and many other countries are considering similar expansion of their
      immunisation programmes at present. In addition, universal immunisation of adults
      (Austria, every 10 years) or targeting high risk groups (e.g., parents of
      newborns and other care-givers to children; Germany) have been recommended. If
      lifelong regular booster doses against pertussis were to be recommended and
      universal implementation was obtained, the authors believe that the morbidity of
      pertussis and its spread to infants can be dramatically reduced, and it is
      possible that the circulation of B. pertussis could be eliminated.

PMID- 16805709
TI  - Update on the therapy of highly aggressive non-Hodgkin's lymphoma.
AB  - This review focuses on the current understanding of the biology of highly
      aggressive non-Hodgkin's lymphomas, such as Burkitt's lymphoma, lymphoblastic
      lymphoma and adult T cell lymphoma/leukaemia. Specifically, this review will
      examine how our increased understanding of the pathophysiology of these diseases
      can be used to develop new therapies.

PMID- 16805710
TI  - Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past, the
      present and the future.
AB  - Complete resection is mandatory in order to achieve a cure in patients with early
      stage non-small cell lung cancer (NSCLC). However, despite complete resection, a
      substantial proportion of patients have disease recurrence, with distant
      metastases being the primary sites of failure. Recent trials have conclusively
      demonstrated the benefit of platinum-based adjuvant therapy in patients with
      resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected
      stage III NSCLC is less clear, with trials showing conflicting results. The role
      of targeted agents in this setting is being investigated. Gene expression
      profiling studies should help direct chemotherapy to those who would actually
      benefit from it, thereby saving others from unnecessary toxicity.

PMID- 16805711
TI  - Application of encapsulated cell technology for retinal degenerative diseases.
AB  - Ophthalmic disorders represent a rapidly growing disease area that is associated
      with the ageing population. Their sight is threatened by age-related macular
      degeneration, diabetic retinopathy, glaucoma and/or retinitis pigmentosa (RP).
      Few effective treatments for these disorders are available at present, in part
      due to lack of effective delivery of therapeutic molecules to the retina.
      Encapsulated cell technology (ECT) allows the controlled, continuous and long
      term administration of protein drugs in the eye, where therapeutic agents are
      needed, and does not subject the host to the systemic exposure. Furthermore, the
      implants can be retrieved, providing an added level of safety. Ciliary
      neurotrophic factor (CNTF) has been shown to protect the retina from degeneration
      in 13 animal models, and ECT-based delivery of CNTF protected photoreceptors in
      the rcd1 dog model of RP.

PMID- 16805712
TI  - American Association of Anatomists meeting on regenerative medicine.
AB  - Several years ago, the American Association of Anatomists (AAA) launched an
      innovative mini-meeting format as part of their annual meeting. The AAA continued
      this tradition by sponsoring a 2-day mini-symposium as a part of its meeting at
      FASEB Experimental Biology, 2006 in San Francisco, CA, USA. This year, the mini
      symposium was focused on the promising and rapidly developing field of
      'regenerative medicine'. The mini-symposium on 'regenerative medicine' included
      four separate but thematically integrated sessions: stem cells for regenerative
      medicine; biomimetic matrices for regenerative medicine; endothelial-mesenchymal
      transformation in cardiovascular regenerative medicine; and tissue engineering
      technologies for regenerative medicine. The goal of these sessions was to
      identify progress and highlight new trends and directions in the evolving field
      of regenerative medicine. It was an exciting 2-day mini-symposium that reviewed
      the differential potential of embryonic and adult stem cells, their role in
      tissue turnover and possible applications in tissue regeneration; identified
      important evolving basic science issues, such as the role of endothelial
      mesenchymal transformation and stem cell recruitment in cardiovascular
      regenerative medicine; and, finally, clearly demonstrated how understanding basic
      scientific principles can be translated into novel cell therapeutics and tissue
      engineering modalities. The workshop also demonstrated the multidisciplinary
      (speakers included stem cell and developmental biologists, chemical engineers,
      tissue engineers, biophysicists, mathematicians and surgeons) and international
      (speakers represented US, Japan, Canada, Switzerland and Korea) character of
      ongoing efforts in the area of regenerative medicine and stem cell biology,
      impressive progress in this field, and confirmed the strong potential for
      clinical translation of emerging regenerative medicine technologies.

PMID- 16805713
TI  - Treating allergic rhinitis and asthma: different sides of the same fence.
AB  - Allergic asthma and rhinitis are highly prevalent diseases. Although they are
      diagnosed and treated separately, many patients suffer from both. There is data
      suggesting that they can be considered as manifestations of the same disease or
      syndrome, but in different locations. This article discusses the evidence
      favouring a joint clinical approach, and the main therapeutic tactics to achieve
      disease control; tries to establish the importance of isolated and adjuvant
      treatment of rhinitis and asthma, highlighting a small number of clinical studies
      regarding the subject; and indicates points for future research.

PMID- 16805714
TI  - Biological agents versus chemotherapy in the treatment of colorectal cancer.
AB  - Biological agents are commonly incorporated as an adjunct to cytotoxic
      chemotherapy in the treatment of patients with advanced colorectal cancer. In
      contrast to cytotoxic chemotherapy, biological agents have minimal single agent
      activity and are largely considered to be cytostatic. Recent data supports the
      use of either combination regimens with chemotherapy and/or biological therapy.
      Interest in combining biological agents of co-existing molecular pathways is the
      most recent strategic approach. However, with the advent of these novel
      therapies, questions have arisen regarding appropriate clinical indication and
      potential treatment-related toxicities. The role of biological agents in the
      treatment of colorectal cancer and their role in contrast to cytotoxic
      chemotherapy will be explored.

PMID- 16805715
TI  - Follicular lymphoma: today's treatments and tomorrow's targets.
AB  - Over the past two decades, the incidence of follicular lymphoma has increased.
      Contemporary treatments include combinations of chemotherapy and monoclonal
      antibodies, radioimmunotherapy, new targeted agents and stem-cell
      transplantation. Prognostic tools are becoming more important in helping
      clinicians and patients decide on the most appropriate therapeutic regimens. Gene
      expression profiling and biomarkers are promising additions to this
      armamentarium. When patients do require therapy, the addition of rituximab to
      chemotherapy seems to improve remission duration and may improve overall
      survival. Radioimmunotherapy capitalises on the capacity to target radiation
      directly to malignant cells, and is currently approved for the treatment of
      relapsed/refractory follicular lymphoma. Further investigation is needed to
      clarify the role of stem-cell transplantation in follicular lymphoma. Only well
      designed clinical trials can provide answers to the many questions that remain
      regarding the optimal treatment and sequence of treatments for patients with
      follicular lymphoma.

PMID- 16805716
TI  - Pharmacoeconomic considerations with statin therapy.
AB  - Statins have been shown to reduce morbidity and mortality in patients with and
      without coronary heart disease, and in patients with elevated and normal or
      average cholesterol levels. Economic evaluations of these mortality trials have
      demonstrated statins to be cost-effective. As these trials were placebo
      comparisons, their results are now of limited use in guiding the drug therapy
      selection process. The more relevant questions today are focused on ways of
      optimising statin therapy. More recent studies have found that more intensive
      statin therapy, using high doses of these agents that produce substantially
      greater reductions in low-density lipoprotein cholesterol, are associated with
      greater benefit than less intensive statin therapy. These trials suggest that
      statins with greater efficacy in reducing low-density lipoprotein cholesterol,
      would be preferred over less effective statins. So far, economic analyses of
      these comparative studies have not been published. These economic studies are
      needed to support formulary and drug therapy selection decisions regarding
      statins.

PMID- 16805717
TI  - Managing psychiatric disorders with antidiabetic agents: translational research
      and treatment opportunities.
AB  - The objective of this paper is to synthesise extant studies describing the
      neurotherapeutic effects of antidiabetic agents in neuropsychiatric disorders.
      The authors conducted a MedLine search of all English-language articles published
      between 1966 and March 2006. The search terms were the nonproprietary names of
      established and putative antidiabetic agents (e.g., insulin, insulin
      secretagogues and sensitisers) cross-referenced with the individual names of
      Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R/IV/-TR-defined
      mood, psychotic, anxiety and dementing disorders. The search was augmented with a
      manual review of article reference lists. Contemporary models of disease
      pathophysiology in major depressive disorder, bipolar disorder and several
      dementing disorders (e.g., Alzheimer's disease) emphasise alterations in cellular
      plasticity and cytoarchitecture, with associated regional abnormalities in
      neuronal and glial density and morphology. Antidiabetic treatments (e.g.,
      thiazolidinediones) may be capable of attenuating this pathological process via
      disparate mechanisms (e.g., neuroprotective, neurotrophic, anti-inflammatory).
      Enhanced insulin signalling with antidiabetic treatments may preserve and/or
      augment cognitive function in several neuropsychiatric disorders. Antidiabetic
      treatments, which maintain euglycaemia, hold promise as potent and clinically
      significant therapeutic interventions for several neuropsychiatric disorders.

PMID- 16805718
TI  - Available treatment options for the management of Lambert-Eaton myasthenic
      syndrome.
AB  - Lambert-Eaton myasthenic syndrome is a rare, but reasonably well-understood,
      antibody-mediated autoimmune disease that is caused by serum auto-antibodies and
      results in muscle weakness and autonomic dysfunction. One half of the patients
      have an idiopathic form, the other half a tumour-associated form of the disease.
      Three randomised trials and a large number of smaller clinical studies have
      resulted in a number of drugs becoming available for the treatment of Lambert
      Eaton myasthenic syndrome. Several drugs are available for the symptomatic
      treatment of the disease, including guanidine, aminopyridines or
      acetylcholinesterase inhibitors. Other therapies aim to deplete the serum
      autoantibodies or to suppress the immune system. For this purpose,
      immunomodulating strategies, such as intravenous immunoglobulins or
      plasmapheresis, or several immunosuppressive agents are available. Chemotherapy
      has successfully ameliorated the course of disease in Lambert-Eaton myasthenic
      syndrome patients with an underlying tumour.

PMID- 16805719
TI  - Bortezomib for multiple myeloma.
AB  - The ubquitin-proteasome pathway is a key regulator of homeostasis within cells,
      degrading misfolded or redundant proteins, and also those involved in mediating
      transcription, cell-cycle progression and apoptosis. Inhibition of the 26S
      proteasome results in accumulation of such proteins and ultimately leads to cell
      death. Malignant cells are more susceptible to proteasome inhibition due to their
      higher proliferation rates, protein production and their dependence on anti
      apoptotic molecules for cell survival. Bortezomib has recently gained European
      Commission approval for the treatment of relapsed multiple myeloma on the basis
      of clinical trials demonstrating its efficacy, tolerability and superiority to
      high-dose dexamethasone. Preclinical data demonstrates the ability to synergise
      with other chemotherapeutic agents and overcome drug resistance, and hence
      combination studies are underway. This review describes the pharmacology,
      toxicity, preclinical and clinical activity of bortezomib, predominantly in the
      setting of multiple myeloma.

PMID- 16805720
TI  - Everolimus: an immunosuppressive agent in transplantation.
AB  - Everolimus is a novel immunosuppressive agent related to sirolimus. It is a
      proliferation signal inhibitor with an improved pharmacokinetic profile and
      bioavailability compared with sirolimus. Everolimus has been shown to be as
      effective as mycophenolate mofetil in reducing acute rejection in renal
      transplantation. In cardiac transplant recipients, it is superior to azathioprine
      in reducing acute rejection and cardiac allograft vasculopathy. Its use is also
      associated with a decrease in cytomegalovirus infection. However,
      coadministration with calcineurin inhibitors requires careful dose adjustment to
      prevent renal toxicity. Antiproliferative effects of everolimus may abrogate the
      increased risk of malignancy seen in solid organ transplantation.

PMID- 16805721
TI  - Insulin glargine and its place in the treatment of Types 1 and 2 diabetes
      mellitus.
AB  - Insulin treatment in Type 1 and Type 2 diabetes has come a long way since its
      discovery by Banting and Best in 1922. Early insulin therapy was life-saving, but
      was associated with practical problems and had side effects such as lipoatrophy.
      Initial modifications of insulin structure produced several classes of insulins
      with varying pharmacokinetics, but did not sufficiently mimic physiological
      insulin release. Novel long- and short-acting insulin analogues, the so-called
      'designer insulins', developed through genetic engineering in the 1990s, paved
      the way for more physiological insulin therapy, which was theoretically less
      problematic in terms of hypoglycaemia and patient satisfaction. Insulin glargine
      (glargine) was the first DNA-recombinant long-acting insulin analogue. The
      replacement of asparagine with glycine and the addition of two arginine molecules
      in the molecular structure results in modified pharmacokinetics. Consequently,
      glargine has a longer, often 24-h profile, which is described as 'peakless'
      compared with other insulins such as neutral protamine Hagedorn insulin (NPH) and
      insulin ultralente. Since its launch, the use of glargine in Type 1 and Type 2
      diabetes has been extensively reviewed to determine its place in the current
      insulin market. A potential advantage of glargine seems to be a lower risk of
      hypoglycaemia, particularly at night. The UK National Institute of Clinical
      Excellence has recommended that glargine is a treatment option for people with
      Type 1 diabetes. In Type 2 diabetes, it has been advised that glargine only be
      considered for: those who require assistance to administer insulin injections;
      those whose lifestyle is restricted significantly by recurrent symptomatic
      hypoglycaemic episodes; or those who would otherwise need twice-daily basal
      insulin injections in combination with oral glucose-lowering drugs.

PMID- 16805722
TI  - Trospium chloride: the European experience.
AB  - The primary pharmacological therapy for overactive bladder syndrome is muscarinic
      receptor antagonists. Muscarinic receptor blockade is effective in decreasing the
      symptoms of urinary urgency and urgency incontinence, but can be associated with
      troublesome complications, such as dry mouth, blurred vision, constipation and
      CNS side effects. Trospium chloride, an antimuscarinic medication, has been
      available in Europe for > 20 years and has recently been approved by the FDA for
      the treatment of overactive bladder. Trospium chloride is a quaternary amine that
      is minimally metabolised, not highly protein bound and, importantly, has not been
      demonstrated to cross the unaltered blood-brain barrier in healthy volunteers.
      Some characteristics of this unique antimuscarinic agent and the European
      experience with trospium chloride are reviewed in this article.

PMID- 16805723
TI  - Update on daptomycin: the first approved lipopeptide antibiotic.
AB  - Daptomycin, the first approved member of the lipopeptide antibiotic class,
      exhibits potent bactericidal in vitro activity against most Gram-positive
      bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin
      resistant Enterococcus species and penicillin-resistant Streptococcus species.
      Since its approval in 2003 for the treatment of complicated skin and skin
      structure infections, several review articles have summarised daptomycin's
      mechanism of action, pharmacokinetics, pharmacodynamics, clinical trials and
      safety profiles. The objective of this paper is to summarise past information
      with a focus on the latest susceptibility data of isolates collected worldwide,
      new pharmacodynamic studies, clinical data regarding bacteraemia/endocarditis and
      postmarketing surveillance in the treatment of skin and skin-structure
      infections.

PMID- 16805725
TI  - Overcoming resistance with designer immunotoxins.
AB  - Normal human serum contains apolipoprotein L-I (apoL-I), which lyses African
      trypanaosomes. Resistant forms, such as Trypanosoma brucei rhodesiense express
      apoL-I-neutralising serum resistance-associated protein, which enables this
      parasite to infect humans and cause human African trypanosomiasis. This paper
      describes the construction of a mutant apoL-I conjugated to a nanobody that
      targets the variant surface glycoprotein of trypanosomes. Treatment with this
      engineered immunotoxin has resulted in both alleviating and curative effects on
      chronic and acute infections of mice with normal human serum-resistant and 
      sensitive trypanosomes.

PMID- 16805724
TI  - The levodopa wearing-off phenomenon in Parkinson's disease: pharmacokinetic
      considerations.
AB  - Levodopa is the most efficacious treatment in the management of Parkinson's
      disease. Unfortunately, chronic use of traditional levodopa/dopa decarboxylase
      inhibitor formulations is associated with the development of complications, such
      as wearing-off and dyskinesia. In an attempt to avoid these complications, some
      physicians delay the introduction of levodopa or employ levodopa-sparing
      strategies; however, these strategies are frequently suboptimal for patients. As
      most patients require the superior efficacy of levodopa during the course of
      their disease, an appreciation of the changing response to levodopa over time and
      an understanding of the pharmacokinetic principles underlying the development of
      complications such as wearing-off is essential in the long-term management of the
      patient.

PMID- 16805726
TI  - A role for ethylene in the phytochrome-mediated control of vegetative
      development.
AB  - Members of the phytochrome family of photoreceptors play key roles in vegetative
      plant development, including the regulation of stem elongation, leaf development
      and chlorophyll accumulation. Hormones have been implicated in the control of
      these processes in de-etiolating seedlings. However, the mechanisms by which the
      phytochromes regulate vegetative development in more mature plants are less well
      understood. Pea (Pisum sativum) mutant plants lacking phytochromes A and B, the
      two phytochromes present in this species, develop severe defects later in
      development, including short, thick, distorted internodes and reduced leaf
      expansion, chlorophyll content and CAB gene transcript level. Studies presented
      here indicate that many of these defects in phyA phyB mutant plants appear to be
      due to elevated ethylene production, and suggest that an important role of the
      phytochromes in pea is to restrict ethylene production to a level that does not
      inhibit vegetative growth. Mutant phyA phyB plants produce significantly more
      ethylene than WT plants, and application of an ethylene biosynthesis inhibitor
      rescued many aspects of the phyA phyB mutant phenotype. This deregulation of
      ethylene production in phy-deficient plants appears likely to be due, at least in
      part, to the elevated transcript levels of key ethylene-biosynthesis genes. The
      phytochrome A photoreceptor appears to play a prominent role in the regulation of
      ethylene production, as phyA, but not phyB, single-mutant plants also exhibit a
      phenotype consistent with elevated ethylene production. Potential interactions
      between ethylene and secondary plant hormones in the control of the phy-deficient
      mutant phenotype were explored, revealing that ethylene may inhibit stem
      elongation in part by reducing gibberellin levels.

PMID- 16805727
TI  - Specific cleavage of ribosomal RNA and mRNA during victorin-induced apoptotic
      cell death in oat.
AB  - Here we report that rRNA and mRNA are specifically degraded in oat (Avena sativa
      L.) cells during apoptotic cell death induced by victorin, a host-selective toxin
      produced by Cochliobolus victoriae. Northern analysis indicated that rRNA species
      from the cytosol, mitochondria and chloroplasts were all degraded via specific
      degradation intermediates during victorin-induced apoptotic cell death but, in
      contrast, they were randomly digested in necrotic cell death induced by 30 mM
      CuSO(4) and heat shock. This indicates that specific rRNA cleavage could be
      controlled by an intrinsic program. We also observed specific cleavage of mRNA of
      housekeeping genes such as actin and ubiquitin during victorin-induced cell
      death. Interestingly, no victorin-induced mRNA degradation was detected with
      stress-responding genes such as PR-1, PR-10 and GPx throughout the experimental
      period. The RNA degradation mostly, but not always, occurred in parallel with DNA
      laddering, but pharmacological studies indicated that these processes are
      regulated by different signaling pathways with some overlapping upstream signals.

PMID- 16805728
TI  - Association of Arabidopsis type-II ROPs with the plasma membrane requires a
      conserved C-terminal sequence motif and a proximal polybasic domain.
AB  - Plant ROPs (or RACs) are soluble Ras-related small GTPases that are attached to
      cell membranes by virtue of the post-translational lipid modifications of
      prenylation and S-acylation. ROPs (RACs) are subdivided into two major subgroups
      called type-I and type-II. Whereas type-I ROPs terminate with a conserved CaaL
      box and undergo prenylation, type-II ROPs undergo S-acylation on two or three C
      terminal cysteines. In the present work we determined the sequence requirement
      for association of Arabidopsis type-II ROPs with the plasma membrane. We
      identified a conserved sequence motif, designated the GC-CG box, in which the
      modified cysteines are flanked by glycines. The GC-CG box cysteines are separated
      by five to six mostly non-polar residues. Deletion of this sequence or the
      introduction of mutations that change its nature disrupted the association of
      ROPs with the membrane. Mutations that changed the GC-CG box glycines to alanines
      also interfered with membrane association. Deletion of a polybasic domain
      proximal to the GC-CG box disrupted the plasma membrane association of AtROP10. A
      green fluorescent protein fusion protein containing the C-terminal 25 residues of
      AtROP10, including its polybasic domain and GC-CG box, was primarily associated
      with the plasma membrane but a similar fusion protein lacking the polybasic
      domain was exclusively localized in the soluble fraction. These data provide
      evidence for the minimal sequence required for plasma membrane association of
      type-II ROPs in Arabidopsis and other plant species.

PMID- 16805729
TI  - Caterpillar-elicited methanol emission: a new signal in plant-herbivore
      interactions?
AB  - Plants release into the atmosphere large quantities of volatile organic compounds
      (VOCs), of which methanol (MeOH), a putative waste product, is the second most
      abundant. Using online proton-transfer-reaction mass spectrometry (PTR-MS), we
      demonstrate that when Manduca sexta larvae attack Nicotiana attenuata plants, the
      wound-induced release of MeOH dramatically increases. The sustained MeOH emission
      24 h after herbivore feeding is already substantially greater than the release of
      the well-characterized green-leaf VOC E-2-hexenal. Herbivore attack and treatment
      of puncture wounds with larval oral secretions (OS) increased the transcript
      accumulation and activity of leaf pectin methylesterases (PMEs), and decreased
      the degree of pectin methylation, as determined by (1)H-NMR; therefore, we
      propose that the released MeOH originates from the activation of PMEs by
      herbivore attack. The herbivore- and OS-elicited MeOH results not from the
      activity of previously characterized elicitors in OS but from a pH shift at the
      wound site when larval OS (pH 8.5-9.5) are introduced into the wounds during
      feeding. Applying MeOH to plants in quantities that mimic the herbivory-elicited
      release decreases the activity of the potent plant defense proteins trypsin
      proteinase inhibitors (TPI), and increases the performance of the attacking
      larvae. The pH of lepidopteran larvae regurgitants is commonly very high, and the
      MeOH released during feeding that is elicited by the pH change at the wound site
      functions as a quantitative signal that influences the outcome of the plant
      herbivore interaction.

PMID- 16805730
TI  - Crosstalk between jasmonic acid, ethylene and Nod factor signaling allows
      integration of diverse inputs for regulation of nodulation.
AB  - Plant hormones interact at many different levels to form a network of signaling
      pathways connected by antagonistic and synergistic interactions. Ethylene and
      jasmonic acid both act to regulate the plant's responsiveness to a common set of
      biotic stimuli. In addition ethylene has been shown to negatively regulate the
      plant's response to the rhizobial bacterial signal, Nod factor. This regulation
      occurs at an early step in the Nod factor signal transduction pathway, at or
      above Nod factor-induced calcium spiking. Here we show that jasmonic acid also
      inhibits the plant's responses to rhizobial bacteria, with direct effects on Nod
      factor-induced calcium spiking. However, unlike ethylene, jasmonic acid not only
      inhibits spiking but also suppresses the frequency of calcium oscillations when
      applied at lower concentrations. This effect of jasmonic acid is amplified in the
      ethylene-insensitive mutant skl, indicating an antagonistic interaction between
      these two hormones for regulation of Nod factor signaling. The rapidity of the
      effects of ethylene and jasmonic acid on Nod factor signaling suggests direct
      crosstalk between these three signal transduction pathways. This work provides a
      model by which crosstalk between signaling pathways can rapidly integrate
      environmental, developmental and biotic stimuli to coordinate diverse plant
      responses.

PMID- 16805731
TI  - Functional and signaling mechanism analysis of rice CRYPTOCHROME 1.
AB  - Cryptochromes (CRY) are blue-light photoreceptors that mediate various light
      responses, such as inhibition of hypocotyl elongation, enhancement of cotyledon
      expansion, anthocyanin accumulation and stomatal opening in Arabidopsis. The
      signaling mechanism of Arabidopsis CRY is mediated through direct interaction
      with COP1, a negative regulator of photomorphogenesis. CRY has now been
      characterized in tomato, pea, moss and fern, but its function in monocots is
      largely unknown. Here we report the function and basic signaling mechanism of
      rice cryptochrome 1 (OsCRY1). Overexpresion of OsCRY1b resulted in a blue light
      dependent short hypcotyl phenotype in Arabidopsis, and a short coleoptile, leaf
      sheath and leaf blade phenotype in rice (Oryza sativa). On fusion with beta
      glucuronidase (GUS), the C-terminal domain of either OsCRY1a (OsCCT1a) or OsCRY1b
      (OsCCT1b) mediated a constitutive photomorphogenic (COP) phenotype in both
      Arabidopsis and rice, whereas OsCCT1b mutants corresponding to missense mutations
      in previously described Arabidopsis cry1 alleles failed to confer a COP
      phenotype. Yeast two-hybrid and subcellular co-localization studies demonstrated
      that OsCRY1b interacted physically with rice COP1 (OsCOP1). From these results,
      we conclude that OsCRY1 is implicated in blue-light inhibition of coleoptile and
      leaf elongation during early seedling development in rice, and that the signaling
      mechanism of OsCRY1 involves direct interaction with OsCOP1.

PMID- 16805732
TI  - Transcriptional regulators of stamen development in Arabidopsis identified by
      transcriptional profiling.
AB  - In Arabidopsis, jasmonate is required for stamen and pollen maturation. Mutants
      deficient in jasmonate synthesis, such as opr3, are male-sterile but become
      fertile when jasmonate is applied to developing flower buds. We have used ATH1
      oligonucleotide arrays to follow gene expression in opr3 stamens for 22 h
      following jasmonate treatment. In these experiments, a total of 821 genes were
      specifically induced by jasmonate and 480 genes were repressed. Comparisons with
      data from previous studies indicate that these genes constitute a stamen-specific
      jasmonate transcriptome, with a large proportion (70%) of the genes expressed in
      the sporophytic tissue but not in the pollen. Bioinformatics tools allowed us to
      associate many of the induced genes with metabolic pathways that are probably
      upregulated during jasmonate-induced maturation. Our pathway analysis led to the
      identification of specific genes within larger families of homologues that
      apparently encode stamen-specific isozymes. Extensive additional analysis of our
      dataset identified 13 transcription factors that may be key regulators of the
      stamen maturation processes triggered by jasmonate. Two of these transcription
      factors, MYB21 and MYB24, are the only members of subgroup 19 of the R2R3 family
      of MYB proteins. A myb21 mutant obtained by reverse genetics exhibited shorter
      anther filaments, delayed anther dehiscence and greatly reduced male fertility. A
      myb24 mutant was phenotypically wild-type, but production of a myb21myb24 double
      mutant indicated that introduction of the myb24 mutation exacerbated all three
      aspects of the myb21 phenotype. Exogenous jasmonate could not restore fertility
      to myb21 or myb21myb24 mutant plants. Together with the data from transcriptional
      profiling, these results indicate that MYB21 and MYB24 are induced by jasmonate
      and mediate important aspects of the jasmonate response during stamen
      development.

PMID- 16805733
TI  - Katanin's severing activity favors bundling of cortical microtubules in plants.
AB  - Higher plant cells exhibit interphase microtubule arrays specific to plants,
      which are essential for their developmental program. These cortical microtubules
      (CMT) consist of a population of highly dynamic microtubules that are usually
      organized into bundles in the cortex of the cells. The organization of CMT is
      intimately linked to the acquisition of specialized functions, and
      subsequentchanges in their distribution affect their properties. The mechanisms
      underlying the formation and the distribution of CMT are still unclear, and
      little is known about the proteins that are involved in this phenomenon. Here we
      investigated the putative role of katanin, the only known plant microtubule
      severing protein, in the organization of CMT. We generated transgenic Arabidopsis
      lines that overexpress katanin under the control of an ethanol-inducible
      promoter. In response to an induced overexpression of katanin, CMT organized into
      numerous and thick bundles, which ultimately depolymerized. From the analyses of
      CMT patterns together with recent data on CMT dynamics, we propose that, in
      interphase cells, katanin's main activity is to free CMT, generating motile
      microtubules that incorporate into bundles.

PMID- 16805734
TI  - Nt-RhoGDI2 regulates Rac/Rop signaling and polar cell growth in tobacco pollen
      tubes.
AB  - Rac/Rop-type Rho-family small GTPases accumulate at the plasma membrane in the
      tip of pollen tubes and control the polar growth of these cells. Nt-RhoGDI2, a
      homolog of guanine nucleotide dissociation inhibitors (GDIs) regulating Rho
      signaling in animals and yeast, is co-expressed with the Rac/Rop GTPase Nt-Rac5
      specifically in tobacco (Nicotiana tabacum) pollen tubes. The two proteins
      interact with each other in yeast two-hybrid assays, preferentially when Nt-Rac5
      is prenylated. Transient over-expression of Nt-Rac5 and Nt-RhoGDI2 depolarized or
      inhibited tobacco pollen tube growth, respectively. Interestingly, pollen tubes
      over-expressing both proteins grew normally, demonstrating that the two proteins
      functionally interact in vivo. Nt-RhoGDI2 was localized to the pollen tube
      cytoplasm and effectively transferred co-over-expressed YFP-Nt-Rac5 fusion
      proteins from the plasma membrane to this compartment. A single amino acid
      exchange (R69A), which abolished binding to Nt-RhoGDI2, caused Nt-Rac5 to be mis
      localized to the flanks of pollen tubes and strongly compromised its ability to
      depolarize pollen tube growth upon over-expression. Based on these observations,
      we propose that Nt-RhoGDI2-mediated recycling of Nt-Rac5 from the flanks of the
      tip to the apex has an essential function in the maintenance of polarized Rac/Rop
      signaling and cell expansion in pollen tubes. Similar mechanisms may generally
      play a role in the polarized accumulation of Rho GTPases in specific membrane
      domains, an important process whose regulation has not been well characterized in
      any cell type to date.

PMID- 16805735
TI  - Characterization and functional analysis of ABSCISIC ACID INSENSITIVE3-like genes
      from Physcomitrella patens.
AB  - Although the moss Physcomitrella patens is known to respond to abscisic acid
      (ABA) by activating gene expression, the transcriptional components involved have
      not been characterized. Initially, we used the ABA-responsive Em promoter from
      wheat linked to beta-glucuronidase (GUS) to determine whether ABI3/VP1,
      transcriptional regulators in the ABA-signaling pathway in angiosperms, were
      similarly active in the ABA response of P. patens. We show by particle
      bombardment that ABI3 and VP1 affect Em-GUS expression in P. patens in a manner
      similar to angiosperms. We also show the involvement of ABI1 in the pathway,
      utilizing the abi1-1 mutant allele. We isolated three ABI3-like genes from P.
      patens. Using an Em-like ABA-responsive promoter from P. patens (PpLea1), we
      demonstrate that PpABI3A, only in the presence of ABA, strongly enhances PpLea1
      GUS expression in P. patens. PpABI3A also enhances ABA-induced Em-GUS expression
      in P. patens. In barley aleurone, PpABI3A transactivates Em-GUS but to a lesser
      extent than VP1 and ABI3. PpABI3A:GFP is localized to the nucleus of both
      protonemal cells and barley aleurone, indicating that the nuclear localization
      signals are conserved. We show that at least a part of the inability of PpABI3A
      to fully complement the phenotypes of the Arabidopsis abi3-6 mutant is due to a
      weak interaction between PpABI3A and the bZIP transcription factor ABI5, as
      assayed functionally in barley aleurone and physically in the yeast-two-hybrid
      assay. Our data clearly demonstrate that P. patens will be useful for comparative
      structural and functional studies of components in the ABA-response pathway such
      as ABI3.

PMID- 16805736
TI  - Impaired sucrose induction1 encodes a conserved plant-specific protein that
      couples carbohydrate availability to gene expression and plant growth.
AB  - To identify the molecular mechanisms underlying carbohydrate allocation to
      storage processes, we have isolated mutants in which the sugar induction of
      starch biosynthetic gene expression was impaired. Here we describe the IMPAIRED
      SUCROSE INDUCTION1 (ISI1) gene, which encodes a highly conserved plant-specific
      protein with structural similarities to Arm repeat proteins. ISI1 is
      predominantly expressed in the phloem of leaves following the sink-to-source
      transition during leaf development, but is also sugar-inducible in mesophyll
      cells. Soil-grown isi1 mutants show reduced plant growth and seed set compared to
      wild-type Arabidopsis. This growth reduction is not due to reduced carbohydrate
      availability or a defect in sucrose export from mature leaves, suggesting that
      isi1 mutant plants do not utilize available carbohydrate resources efficiently.
      ISI1 interacts synergistically with, but is genetically distinct from, the
      abscisic acid (ABA) signalling pathway controlling sugar responses via ABI4. Our
      data show that ISI1 couples the availability of carbohydrates to the control of
      sugar-responsive gene expression and plant growth.

PMID- 16805737
TI  - Establishment of a patterned GAL4-VP16 transactivation system for discovering
      gene function in rice.
AB  - A binary GAL4-VP16-UAS transactivation system has been established in rice (Oryza
      sativa L.) in this study for the discovery of gene functions. This binary system
      consists of two types of transgenic lines, pattern lines and target lines. The
      pattern lines were produced by transformation of Zhonghua 11, a japonica
      cultivar, with a construct consisting of the transactivator gene GAL4-VP16
      controlled by a minimal promoter and the GUSplus reporter controlled by the
      upstream activation sequence (UAS; cis-element to GAL4). Target lines were
      generated by transformation of Zhonghua 11 with constructs carrying the EGFP
      reporter and target genes of interest, both controlled by the UAS but in opposite
      directions. Hybrid plants were obtained by crossing target lines of 10 putative
      transcription factor genes from rice with six pattern lines showing expression in
      anther, stigma, palea, lemma and leaves. The EGFP and target genes perfectly co
      expressed in hybrid plants with the same expression patterns as in the pattern
      lines. Various phenotypic changes, such as delayed flowering, multiple pistils,
      dwarfism, narrow and droopy leaves, reduced tillers, growth retardation and
      sterility, were induced as a result of the expression of the target genes. It is
      concluded that this transactivation system can provide a useful tool in rice to
      unveil latent functions of unknown or known genes.

PMID- 16805738
TI  - Quantitative in situ assay of salicylic acid in tobacco leaves using a
      genetically modified biosensor strain of Acinetobacter sp. ADP1.
AB  - Salicylic acid (SA) plays important roles in plants, most notably in the
      induction of systemic acquired resistance (SAR) against pathogens. A non
      destructive in situ assay for SA would provide new insights into the functions of
      SA in SAR and other SA-regulated phenomena. We assessed a genetically engineered
      strain of Acinetobacter sp. ADP1, which proportionally produces bioluminescence
      in response to salicylates including SA and methylsalicylate, as a reporter for
      salicylate accumulation in the apoplast of plant leaves. SA was measured
      quantitatively in situ in NN genotype tobacco (Nicotiana tabacum L. cv Xanthi-nc)
      leaves inoculated with tobacco mosaic virus (TMV). The biosensor revealed
      accumulation of apoplastic SA before the visible appearance of hypersensitive
      response (HR) lesions. When the biosensor was infiltrated into TMV-inoculated
      leaves displaying HR lesions at 90 and 168 h post-inoculation, salicylate
      accumulation was detected predominantly in tissues surrounding the lesions and in
      veins adjacent to HR lesions. These images are consistent with previous data
      demonstrating that SA accumulation occurs prior to and following the onset of
      visible HR lesions. We also used the biosensor to observe apoplastic SA
      accumulation in tobacco leaves inoculated with virulent and HR-eliciting strains
      of the bacterial plant pathogen Pseudomonas syringae. The work demonstrates that
      the Acinetobacter sp. ADP1 biosensor is a useful new tool to non-destructively
      assay salicylates in situ and to map their spatial distribution in plant tissues.

PMID- 16805739
TI  - Improvement of seed yields under boron-limiting conditions through overexpression
      of BOR1, a boron transporter for xylem loading, in Arabidopsis thaliana.
AB  - Soil fertilization is a common practice in modern agriculture, undertaken to
      prevent nutrient deficiency in crops. However, fertilization is costly and causes
      environmental pollution. The cultivation of plants that tolerate low nutrient
      supplies may circumvent this problem. Here, we report the generation of
      Arabidopsis thaliana plants that tolerate boron (B)-deficient conditions due to
      the overexpression of BOR1, an efflux B transporter that is required for
      efficient xylem loading of B. In several independently generated transgenic
      plants expressing BOR1 or BOR1-GFP under the control of the cauliflower mosaic
      virus 35S RNA promoter, root-to-shoot translocation of B was enhanced and shoot
      growth was greater under B-limiting conditions compared with wild-type plants. In
      addition, the transgenic plants showed increased translocation of B, especially
      to the shoot apex, and set seed normally under B-limiting conditions, under which
      wild-type plants failed to set seed. This study therefore reports plants that
      show improved seed yields compared with wild-type under nutrient-deficient
      conditions as a result of increased production of an essential mineral nutrient
      transporter.

PMID- 16805741
TI  - Am I bothered?

PMID- 16805742
TI  - Overactive bladder made ridiculously simple?

PMID- 16805743
TI  - One man and his scope.

PMID- 16805744
TI  - Less patient discomfort by one-man colonoscopy examination.
AB  - A randomised prospective trial compared safety and patient tolerance for one-man
      method with two-man method undergoing colonoscopy. Eighty patients were
      randomized to 1 of 2 groups: the two-man method group (n = 40); or the one-man
      method group (n = 40). All colonoscopic examinations were performed by the same
      endoscopist to reduce skill-based variation. Patient tolerance for colonoscopy
      was evaluated with a numerical rating scale ranging from 0 for painless to 5 for
      maximal pain. Cardiopulmonary parameters were recorded during the procedure.
      Patients receiving one-man method had lower pain score than two-man method. The
      length of the scope reach to the cecum was shorter in the one-man group than the
      two-man group. The patients underwent two-man colonoscopy had higher maximum
      increase in heart rate during the procedure compared with one-man group. One-man
      colonoscopy can improve patient tolerance and reduces patient pain by decreasing
      the redundancy of colonoscope during the procedure.

PMID- 16805745
TI  - Cardiac safety of rivastigmine in Lewy body and Parkinson's disease dementias.
AB  - Cholinesterase inhibition in patients with Alzheimer's disease (AD) may affect
      heart rate, sometimes inducing bradycardia. Additional cardiac safety
      considerations apply in patients with dementia with Lewy bodies (DLB) and
      Parkinson's disease (PDD), in whom cardiovascular autonomic nervous system
      dysfunction is common. We conducted a review of the safety data available for
      rivastigmine in these two conditions. A modest reduction in the mean heart rate
      of 1.5-2 bpm was seen. No clinically meaningful treatment differences in
      bradycardia or ECG abnormalities were apparent. Compared with placebo,
      rivastigmine appeared to be associated with fewer vascular disorder adverse
      events (AEs) (p = 0.002) and fewer AEs of syncope (p = 0.018) in PDD patients (n
      = 541). A smaller randomised, placebo-controlled study of rivastigmine in DLB (n
      = 120) showed similar findings. Rivastigmine appears to have a favourable cardiac
      safety profile in PDD and DLB patients.

PMID- 16805746
TI  - Treatment effects of rivastigmine on cognition, performance of daily living
      activities and behaviour in Alzheimer's disease in an outpatient geriatric
      setting.
AB  - We investigated rivastigmine effectiveness in 84 Alzheimer outpatients, with a
      special focus on behavioural problems. Cognition, activities in daily living
      (ADL) and behaviour were assessed during 30 months. Changes in test results
      between 6 months and baseline were compared with a historical control cohort of
      Alzheimer patients (n = 69) by performing t-tests and calculation of Cohen's d
      and standardised response mean (SRM). During 6 months, rivastigmine showed effect
      on cognition (p < 0.001, Cohen's d = 0.33, SRM = 0.78), ADL (p < 0.001, Cohen's d
      = -0.43, SRM = -0.54) and memory-related behaviour (p = 0.006, Cohen's d = -0.28,
      SRM = -0.28). Depressive behaviour worsened (p = 0.001, Cohen's d = 0.30, SRM =
      0.37) and disruptive behaviour (p = 0.369, Cohen's d = -0.07, SRM = -0.09) was
      not effected by rivastigmine. During 30 months, a gradual decline was shown in
      most domains. Most RMBPC items showed stabilization during 30 months. Improvement
      on disruptive behaviour items and depression items was shown after 6 months of
      treatment in a large proportion of patients in whom behavioural problems were
      present at baseline. In conclusion, a huge discontinuation rate is experienced
      within the first half year of treatment. In the subpopulation of patients who
      continued rivastigmine for 6 months, it shows modest effectiveness on cognition,
      functionality and memory-associated behaviour compared with historical control
      patients. Unfortunately, disruptive behaviour is not altered by rivastigmine
      therapy, and depressive behaviour worsened slightly after initial treatment.
      During 30 months, rivastigmine showed stabilization on numerous behaviour items
      as measured by the RMBPC.

PMID- 16805747
TI  - Which thyroid-stimulating hormone level should be sought in hypothyroid patients
      under L-thyroxine replacement therapy?
AB  - We sought to determine whether relationships exist between level of thyroid
      stimulating hormone (TSH) suppression and cardiovascular risk parameters such as
      plasma homocysteine, C-reactive protein (CRP), fibrinogen, D-dimer and serum
      cholesterol in patients taking L-thyroxine-replacement therapy (LT4-RT). Four
      hundred and two hypothyroid patients under LT4-RT were cross-sectionally
      evaluated. Patients were grouped according to their achieved TSH (mIU/l) levels
      under LT4-RT on an arbitrary manner. Those patients having a TSH value 0.4-2 were
      defined as group 1 (n = 154), a TSH level of 2 to less than 5.5 were defined as
      group 2 (n = 176) and a TSH level of 5.5 to less than 20 with a normal free T3
      and free T4 level were defined as group 3 (n = 72). The three groups of patients
      were also compared with overt hypothyroid patients (n = 71) and healthy controls
      (n = 97). Homocysteine levels (micromol/l) were significantly different between
      the three groups (10.4 +/- 4 for group 1, 11.3 +/- 3.7 for group 2 and 13.5 +/-
      4.7 for group 3; p < 0.01 for all groups). Significant differences in CRP (mg /l)
      levels were present between the three groups (2.6 +/- 2.6 for group 1, 3.3 +/-
      2.9 for group 2 and 4.8 +/- 4.1 for group 3; p < 0.01 for all groups). Univariate
      analysis showed that both homocysteine and CRP levels significantly correlated
      with free T4 and TSH level (p < 0.01 for both groups). No statistically
      significant differences were noticed in respect to fibrinogen and d-dimer levels
      between three groups. In examining the effect of LT4-RT on lipid parameters, a
      tendency towards beneficial effects without achieving statistical significance
      was observed. Practically speaking, a target TSH level of less than 2 might be
      advisable to lower CRP levels and homocysteine levels, and possibly lipid
      parameters.

PMID- 16805748
TI  - Optimisation of thyroid hormone replacement using an automated thyroid register.
AB  - The high prevalence of thyroid dysfunction requires an efficient and effective
      means of monitoring and adjustment. We compared the current network of 12,524
      patients with thyroid dysfunction with register data prior to 1991 to examine the
      precision of thyroxine replacement in patients with hypothyroidism and assess
      locally changing trends in treatment of hyperthyroidism. Since 1991, due to the
      associated adverse effects of a suppressed thyroid-stimulating hormone (TSH)
      (<0.03 mU/l), the network has facilitated a significant reduction in the
      proportion of thyroxine-treated patients with TSH suppression from 58.5% before
      1991 to 9.2 +/- 3.8% thereafter. Since 1991, there has been an increased use of
      radioiodine by 14.3% [95% confidence interval (95% CI): 10.6-17.8] and a reduced
      use of thyroidectomy by 12.3% (95% CI: 8.8-15.8) to treat hyperthyroid patients
      compared with before 1991. Between the two treatments, there were no differences
      in subsequent rates of hypothyroidism or mean thyroxine dosage.

PMID- 16805749
TI  - Bacteriology swab in primary total hip arthroplasty-- does it have a role?
AB  - Infection in joint replacement is a devastating complication, and in spite of the
      advances in surgery, it remains a challenge. The rate of deep infection following
      primary hip/knee arthroplasty is between 1% and 2%. The aim of this study was to
      determine whether obtaining bacteriology swabs at the time of surgery could help
      in further reducing the rate of infection following joint arthroplasty. A
      bacteriology swab of the synovial fluid was taken after opening the capsule of
      the hip joint and was sent for culture and sensitivity. Out of 142 swabs sent,
      four (2.1%) were found to be positive. Three of these patients were treated with
      antibiotics after obtaining sensitivities. None of the patients developed deep
      infection. Bacteriology swab in primary joint arthroplasty may have a role and
      may help in further reducing the incidence of deep infection in joint replacement
      surgery.

PMID- 16805750
TI  - An integrated care pathway to save the critically ischaemic diabetic foot.
AB  - This prospective study describes and evaluates the efficacy of an integrated care
      pathway for the management of the critically ischaemic diabetic foot patients by
      a multidisciplinary team. A weekly joint diabetes/vascular/podiatry ward round
      and outpatient clinic was established where patients were assessed within 7 days
      of referral by clinical examination, ankle-brachial-index-pressures, duplex
      angiogram and transcutaneous oxygen pressures. An angiogram +/- angioplasty or
      alternatively a magnetic resonance angiography prior to surgical
      revascularisation was performed in patients deemed not suitable for angioplasty
      based on the above vascular assessment. Between January 2002 and June 2003(18
      months), 128 diabetic patients with lower limb ischaemia were seen. Thirty-four
      (26.6%) patients received medical treatment alone, and 18 (14.1%) were deemed
      'palliative' due to their significant co-morbidities. The remaining 76 (59.4%)
      patients underwent either angioplasty (n = 56), surgical reconstruction (n = 18),
      primary major amputation (n = 2) or secondary amputation after surgical
      revascularisation (n = 1). Minor toe amputations were required in 35 patients.
      The mortality in the intervention group was 14% (11/76). This integrated
      multidisciplinary approach offers a consistent and equitable service to diabetic
      patients with critically ischaemic feet and appears to have a beneficial
      major/minor amputation ratio.

PMID- 16805751
TI  - Seroprevalence of hepatitis C in patients with type 2 diabetes mellitus and non
      diabetic on haemodialysis.
AB  - Type 2 diabetes mellitus (DM) has emerged as the commonest cause of end-stage
      renal disease. Haemodialysis (HD) treatment constitutes a high-risk environment
      for the transmission of hepatitis C virus (HCV). The aim of this study was to
      establish a potential relationship between type 2 DM and HCV infection in HD
      patients. Of the 267 HD patients, 67 (25.1%) had type 2 DM and 200 (74.9%) were
      with diverse aetiology for end-stage renal disease. The serum markers of HCV
      infection were tested by a second-generation enzyme-linked immunosorbent assay
      test for antibodies and by qualitative reverse-transcription polymerase chain
      reaction technique for viral RNA. The overall prevalence of anti-HCV antibodies
      and HCV RNA was found to be 12.7% (34/267) and 10.1% (27/267), respectively.
      Patients with type 2 DM were found to have a higher HCV prevalence compared with
      non-diabetic patients [20.8% (14/67) vs. 10% (20/200)] (p < 0.05). The mean
      period on dialysis of anti-HCV-positive patients with type 2 DM was shorter than
      that observed for anti-HCV-positive non-diabetic patients (43.9 +/- 9.8 months
      vs. 59.7 +/- 28.4 months) (p < 0.05). This study has shown that although the
      period on dialysis of diabetic patients are shorter than non-diabetic patients,
      the prevalence of HCV in HD patients with type 2 DM is higher than that detected
      in non-diabetic HD patients.

PMID- 16805752
TI  - Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects
      on prognosis.
AB  - In non-small-cell lung cancer (NSCLC), stage of the disease is still the most
      important prognostic factor. Other than stage, many biological markers and many
      other prognostic factors are studied to define their effects on prognosis of lung
      cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2
      genes which are important in apoptosis and c-kit, which is a tyrosine kinase
      transmembrane receptor, as well as searched their response to treatment
      modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples
      were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC)
      methods. IHC evaluation was done by the semichantitative method according to the
      distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage
      I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%)
      stage IIIB and three cases (4.4%) were stage IV patients. Their histological
      subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma,
      28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma
      (two patients) and large-cell carcinoma (three patients). The positive
      immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma
      and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%,
      respectively. The positive immune staining rates for c-kit in whole group,
      squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%,
      respectively. We didn't find any correlation with Bax, bcl-2 and c-kit
      expressions and clinicopathological parameters such as age, tumour size, lymph
      node involvement, smoking, stage of the disease, response to radiotherapy and
      chemotherapy. Results are interpreted according to survival; bax and bcl-2
      expressions were not so effective both in whole group and histologically
      subgrouped patients. C-kit expression was also found not related with survival in
      whole group whereas found as a bad prognostic factor in patients with squamous
      cell carcinoma. These findings could indicate that the expression of apoptotic
      pathway markers and c-kit may have a role in the prognosis of early stage NSCLC,
      especially with squamous cell carcinoma subtype.

PMID- 16805753
TI  - Left and right ventricular diastolic functions in patients with rheumatoid
      arthritis without clinically evident cardiovascular disease.
AB  - The aim of this study was to assess the prevalence of diastolic dysfunction of
      the left ventricle (LV) and of the right ventricle in patients with rheumatoid
      arthritis (RA) without clinically evident cardiovascular manifestations and to
      estimate whether there is a correlation between the duration of RA and the degree
      of LV diastolic dysfunction. The study included 81 patients (61 females and 20
      males) with RA without clinically evident heart disease (group 1) and 40 healthy
      subjects (29 females and 11 males) who served as a control group (group 2). Both
      groups were matched for age and sex. Echocardiographic and Doppler studies were
      conducted in all patients with RA and control subjects. There were significant
      differences between patients with RA vs. control group with regard to early
      diastolic flow velocity (E), atrial flow velocity (A) and the E/A ratio (0.68 +/-
      0.19 m/s vs. 0.84 +/- 0.14 m/s, p < 0.001; 0.73 +/- 0.15 m/s vs. 0.66 +/- 0.13
      cm/s, p = 0.01; and 0.97 +/- 0.3 vs. 1.32 +/- 0.37, p < 0.001, respectively).
      There was significant difference between groups regarding the right ventricular
      early diastolic (Er)/atrial (Ar) flow velocities (Er/Ar ratio) (1.07 +/- 0.3 vs.
      1.26 +/- 0.3, p = 0.002). There was a weak correlation between transmitral E/A
      ratio and the duration of RA (r = - 0.22, p = 0.001). Myocardial performance
      index (MPI) appeared to differ little in patients with RA as compared with
      control group (0.51 +/- 0.1 vs. 0.52 +/- 0.2, p = NS). In patients with RA
      without clinically evident cardiovascular disease, the left ventricular diastolic
      function and the right ventricular diastolic function are reduced. Left
      ventricular wall thickness, dimensions, systolic function and MPI were found to
      be normal. LV diastolic function had a weak correlation with the duration of RA.

PMID- 16805754
TI  - Optimising adjuvant endocrine treatment of breast cancer with aromatase
      inhibitors.
AB  - There is mounting evidence that aromatase inhibitors (AIs) are superior to
      tamoxifen as adjuvant treatment for postmenopausal women with oestrogen receptor
      positive breast cancer. Nevertheless, tamoxifen still remains a useful and
      relatively nontoxic treatment, and further work is necessary to determine which
      patients need an AI. In terms of cost-effectiveness, letrozole has been estimated
      to be superior to tamoxifen. Anastrozole, letrozole and exemestane have not been
      compared directly in an adjuvant setting but letrozole proved superior to
      anastrozole in patients with advanced breast cancer. Although tumour receptor
      phenotype may be useful in selection for tamoxifen or AI, the evidence is mixed.
      Optimal sequencing and duration of treatment have yet to be determined. If
      nationally funded and organised trials could be instigated, these would give
      timely and reliable data, so that adjuvant endocrine treatment of breast cancer
      could be tailored to needs of the individual patient.

PMID- 16805755
TI  - Treatment of premature ejaculation.
AB  - Premature ejaculation (PE) is a common problem, the treatment of which has
      received an increasing interest in recent years. Traditional management continues
      to be psychotherapy, with techniques such as the 'squeeze' and 'stop-start' most
      commonly employed. The application of local anaesthetics to the glans to delay
      ejaculation, first described over 60 years ago, continues to be used both in
      medical practice and as an 'over-the-counter' remedy. Over the years, a variety
      of psychopharmacological agents, especially antidepressants, have been described
      as treatments for PE. At the present time, the selective serotonin re-uptake
      inhibitors, licensed for other indications, emerge as the most effective agents
      to delay ejaculation, but none are licensed for the treatment of PE. There
      appears to be a high relapse rate irrespective of the mode of therapy used.

PMID- 16805756
TI  - Review of clinical trials using early acute intervention with oral triptans for
      migraine management.
AB  - Most of the data on triptan use are from clinical trials in which patients were
      instructed to wait until migraine headache pain was moderate/severe in intensity.
      In the real world, patients may hesitate to use a triptan until headache pain is
      moderate/severe because of the cost of these agents or limited supply allowed by
      their health service organisation. However, accumulating data indicate that early
      intervention with an oral triptan when headache pain is still mild may be the
      most effective acute treatment strategy. Economic analyses also support early
      triptan intervention in migraine attacks. Tolerability is expected to be
      particularly important in early intervention, as patients treating mild migraine
      pain may be more reluctant to risk adverse events. Thus, an agent selected for
      use as early intervention should have both a demonstrated efficacy in treating
      mild migraine headache and placebo-like tolerability. This article reviews
      retrospective and prospective clinical trials which investigated the use of
      triptans for early acute migraine therapy.

PMID- 16805757
TI  - Clinical evidence for use of acetyl salicylic acid in control of flushing related
      to nicotinic acid treatment.
AB  - Nicotinic acid (NA) is highly effective and widely used in the management of
      dyslipidaemia. For many patients, the side effect of flushing of the face and
      upper body leads to discontinuation. Flushing with NA is mediated by
      prostaglandins, and as acetyl salicylic acid (ASA, 'aspirin') is a highly
      effective inhibitor of prostaglandin synthesis, there is a rationale for its use
      to prevent or reduce the severity of NA-related flushing. This literature survey
      identified four studies specifically exploring the utility of ASA in preventing
      NA-related flushing in healthy volunteers. Twenty-three NA studies, where ASA was
      mandatory or optional within the protocol, and four studies, where background ASA
      therapy was reported in most participants, were also identified. Although the
      incidence of flushing in studies using ASA was often high, discontinuation rates
      due to flushing were low (mean 7.7%). This figure compares favourably with
      discontinuation rates with NA commonly reported in the literature (up to
      approximately 40%). There is good supportive evidence for the use of ASA in
      reducing the severity of NA-related flushing.

PMID- 16805758
TI  - Statins and the acute coronary syndrome: 'the early bird catches the worm'.
AB  - The early period following an acute coronary syndrome (ACS) is characterised by
      atherosclerotic plaque destabilisation and a pro-coagulant state, and is when
      patients are at highest risk for recurrent cardiovascular events and mortality.
      Statins decrease thrombus formation and increase fibrinolysis, inhibit platelet
      reactivity and aggregation, improve endothelial function in patients with
      coronary artery disease and have a major role in plaque stabilisation. Several
      studies showed that initiation of early statin therapy in these settings may have
      beneficial effects. This review summarises the current data on statins in the
      setting of ACSs. Known and other possible mechanisms of action are described. The
      pathophysiological mechanisms, histological features and biochemical
      characteristics of ACS are different than those with stable coronary disease,
      thereby suggesting that the mechanisms whereby statins exert their benefits in
      ACS may be distinct from those for stable CHD. Initiation of the therapy during
      hospitalisation rather than at the time of hospital discharge may provide
      protection against early recurrent cardiovascular events and also improve
      patients' compliance.

PMID- 16805759
TI  - Inhaled insulin: new technology, new possibilities.
AB  - The prevalence of diabetes is reaching epidemic proportions with an increasing
      need for new therapies. Several new therapies are in development and amongst
      these is inhaled insulin. Inhaled insulin is a novel way of delivering insulin
      and has been shown to have an efficacy comparable to subcutaneous insulin in
      patients with both type 1 and type 2 diabetes. Several inhaled insulin delivery
      systems are currently in development and the first of these, Exubera has recently
      been granted license in Europe and in the USA. In this article we review the
      efficacy and safety profile of Exubera and discuss its potential place in the
      management of diabetes.

PMID- 16805760
TI  - A review of gastrointestinal foreign bodies.
AB  - Gastrointestinal tract (GIT) foreign bodies represent a significant clinical
      problem in the Emergency Department, causing a high degree of financial burden,
      morbidity and mortality. A large variety of foreign bodies are accidentally
      ingested or inserted into the GIT in different age groups. This a retrospective
      review of 38 patients who presented to the Emergency Department with GIT foreign
      bodies between January 2001 and December 2004. Computer database and case note
      search of patients' personal data, nature of the foreign objects and mode of
      entry to the GIT were recorded. There were 30 males and eight females (M : F
      ratio of 3.75:1) with an age range of 10 months to 87 years (median age 25.5
      years). Foreign body ingestion/insertion was accidental in 14 patients,
      deliberate in 11, for anal erotism in 11 and as a result of assault in two cases.
      The median time before presentation was 12 h, and the mean length of hospital
      stay was 1.7 days. Treatment was conservative in 15 patients; five patients had
      gastroscopic retrieval; 15 patients underwent examination under anaesthetic,
      retrieval and proctosigmoidoscopy and three patients underwent laparotomy for
      impacted foreign bodies. GIT foreign body ingestion or insertion is common;
      however, majority of cases can be successfully managed conservatively.

PMID- 16805761
TI  - Short course of linezolid treatment for vancomycin-resistant Enterococcus faecium
      meningitis.
AB  - Enterococci might be one of the meningitis pathogens, but meningitis is rarely
      caused by vancomycin-resistant enterococci. In this report, we present a 69-year
      old man who had the underlying chronic obstructive pulmonary disease with long
      term steroid treatment suffered from a meningitis episode after hospitalisation
      for the urinary tract infection. The cerebrospinal fluid culture of the patient
      grew Enterococcus faecium which was resistant to vancomycin. A vancomycin
      resistant E. faecium was also isolated from the rectal swab of the patient. These
      two E. faecium isolates were found to harbour the vanA gene and to be identical
      by pulsed field gel electrophoresis typing. The patient was treated successfully
      with intravenous linezolid, 600 mg every 12 h for 2 weeks. This was the first
      case of meningitis caused by vancomycin-resistant E. faecium in Taiwan.

PMID- 16805762
TI  - Metoclopramide is not an analgesic: reflection on a premature scientific
      conclusion.

PMID- 16805763
TI  - Symptom-specific efficacy of tolterodine extended release in patients with
      overactive bladder: the IMPACT trial.
AB  - We evaluated the efficacy of tolterodine extended release (ER) for patients' most
      bothersome overactive bladder (OAB) symptom in a primary care setting. Patients
      with OAB symptoms for >or=3 months received tolterodine ER (4 mg q.d.) for 12
      weeks. Among incontinent patients (n = 772), the most bothersome OAB symptoms
      were daytime frequency (28%), urgency urinary incontinence (UUI; 27%), nocturnal
      frequency (26%) and urgency (19%); among continent patients (n = 91), they were
      daytime frequency (47%), nocturnal frequency (42%) and urgency (10%). Sixty-nine
      per cent of patients had one or more comorbid conditions. By week 12, there were
      significant reductions in patients' most bothersome symptom: -80% for UUI, -78%
      for urgency episodes, -40% for nocturnal frequency and -30% for daytime frequency
      (p < 0.0001). The most common adverse events were dry mouth (10%) and
      constipation (4%). In primary care practice, bothersome OAB symptoms can be
      effectively and safely treated with tolterodine ER, even in patients with
      comorbid conditions.

PMID- 16805764
TI  - Tolterodine extended release improves patient-reported outcomes in overactive
      bladder: results from the IMPACT trial.
AB  - We evaluated the effect of tolterodine extended release (ER) on patient- and
      clinician-reported outcomes in a primary care setting. Patients had overactive
      bladder (OAB) symptoms for >or=3 months and were at least moderately bothered by
      their most bothersome symptom, as indicated on the patient-completed OAB Bother
      Rating Scale. Patients completed the Overactive Bladder Questionnaire (OAB-q),
      American Urological Association Symptom Index (AUA-SI), and Patient Perception of
      Bladder Condition at each visit; investigators completed the Clinical Global
      Impression-Improvement at week 12. By week 12, there were statistically
      significant and clinically meaningful decreases on the OAB-q and AUA-SI total and
      subscale scores (p < 0.0001). Seventy-nine per cent of patients experienced some
      improvement in their overall bladder condition. Physicians reported that 68% of
      patients were 'much improved' or 'very much improved'. For symptom-defined
      conditions, patient-reported outcomes are a valuable means for determining
      responses to treatment.

PMID- 16805766
TI  - Common molecular mechanisms in explicit and implicit memory.
AB  - Cellular and molecular studies of both implicit and explicit memory suggest that
      experience-dependent modulation of synaptic strength and structure is a
      fundamental mechanism by which these memories are encoded and stored within the
      brain. In this review, we focus on recent advances in our understanding of two
      types of memory storage: (i) sensitization in Aplysia, a simple form of implicit
      memory, and (ii) formation of explicit spatial memories in the mouse hippocampus.
      These two processes share common molecular mechanisms that have been highly
      conserved through evolution.

PMID- 16805767
TI  - Presynaptic enzymatic neurotoxins.
AB  - Botulinum neurotoxins produced by anaerobic bacteria of the genus Clostridium are
      the most toxic proteins known, with mouse LD50 values in the 1-5 ng/kg range, and
      are solely responsible for the pathophysiology of botulism. These
      metalloproteinases enter peripheral cholinergic nerve terminals and cleave
      proteins of the neuroexocytosis apparatus, causing a persistent, but reversible,
      inhibition of neurotransmitter release. They are used in the therapy of many
      human syndromes caused by hyperactive nerve terminals. Snake presynaptic PLA2
      neurotoxins block nerve terminals by binding to the nerve membrane and catalyzing
      phospholipid hydrolysis with production of lysophospholipids and fatty acids.
      These compounds change the membrane conformation, causing enhanced fusion of
      synaptic vesicle via hemifusion intermediate with release of neurotransmitter
      and, at the same time, inhibition of vesicle fission and recycling. It is
      possible to envisage clinical applications of the lysophospholipid/fatty acid
      mixture to inhibit hyperactive superficial nerve terminals.

PMID- 16805768
TI  - Kiss-and-run and full-collapse fusion as modes of exo-endocytosis in
      neurosecretion.
AB  - Neurotransmitters and hormones are released from neurosecretory cells by
      exocytosis (fusion) of synaptic vesicles, large dense-core vesicles and other
      types of vesicles or granules. The exocytosis is terminated and followed by
      endocytosis (retrieval). More than fifty years of research have established full
      collapse fusion and clathrin-mediated endocytosis as essential modes of exo
      endocytosis. Kiss-and-run and vesicle reuse represent alternative modes, but
      their prevalence and importance have yet to be elucidated, especially in neurons
      of the mammalian CNS. Here we examine various modes of exo-endocytosis across a
      wide range of neurosecretory systems. Full-collapse fusion and kiss-and-run
      coexist in many systems and play active roles in exocytotic events. In small
      nerve terminals of CNS, kiss-and-run has an additional role of enabling nerve
      terminals to conserve scarce vesicular resources and respond to high-frequency
      inputs. Full-collapse fusion and kiss-and-run will each contribute to maintaining
      cellular communication over a wide range of frequencies.

PMID- 16805769
TI  - The p53 family in nervous system development and disease.
AB  - The p53 family, consisting of the tumor suppressors p53, p63 and p73, play a
      vital role as regulators of survival and apoptosis in the developing, adult and
      injured nervous system. These proteins function as key survival and apoptosis
      checkpoints in neurons, acting as either rheostats or sensors responsible for
      integrating multiple pro-apoptotic and survival cues. A dramatic example of this
      checkpoint function is observed in developing sympathetic neurons, where a pro
      survival and truncated form of p73 antagonizes the apoptotic functions of p53 and
      p63. Thus the levels and activities of the different p53 family members may
      ultimately determine whether neurons either live or die during nervous system
      development and disease.

PMID- 16805770
TI  - Intrinsic resistance of neural stem cells to toxic metabolites may make them well
      suited for cell non-autonomous disorders: evidence from a mouse model of Krabbe
      leukodystrophy.
AB  - While transplanted neural stem cells (NSCs) have been shown to hold promise for
      cell replacement in models of a number of neurological disorders, these examples
      have typically been under conditions where the host cells become dysfunctional
      due to a cell autonomous etiology, i.e. a 'sick' cell within a relatively
      supportive environment. It has long been held that cell replacement in a toxic
      milieu would not likely be possible; donor cells would succumb in much the same
      way as endogenous cells had. Many metabolic diseases are characterized by this
      situation, suggesting that they would be poor targets for cell replacement
      therapies. On the other hand, models of such diseases could prove ideal for
      testing the capacity for cell replacement under such challenging conditions. In
      the twitcher (twi ) mouse -- as in patients with Krabbe or globoid cell
      leukodystrophy (GLD), for which it serves as an authentic model -- loss of
      galactocerebrosidase (GalC) activity results in the accumulation of psychosine, a
      toxic glycolipid. Twi mice, like children with GLD, exhibit inexorable
      neurological deterioration presumably as a result of dysfunctional and ultimately
      degenerated oligodendrocytes with loss of myelin. It is believed that GLD
      pathophysiology is related to a psychosine-filled environment that kills not only
      host oligodendrocytes but theoretically any new cells placed into that milieu.
      Through the implantation of NSCs into the brains of both neonatal and
      juvenile/young adult twi mice, we have determined that widespread oligodendrocyte
      replacement and remyelination is feasible. NSCs appear to be intrinsically
      resistant to psychosine -- more so in their undifferentiated state than when
      directed ex vivo to become oligodendrocytes. This resistance can be enhanced by
      engineering the NSCs to over-express GalC. Some twi mice grafted with such
      engineered NSCs had thicker white tracts and lived 2-3 times longer than
      expected. While their brains had detectable levels of GalC, it was probably more
      significant that their psychosine levels were lower than in twi mice that died at
      a younger age. This concept of resistance based on differentiation state extended
      to human NSCs which could similarly survive within the twi brain. Taken together,
      these results suggest a number of points regarding cellular therapies against
      degenerative diseases with a prominent cell non-autonomous component: Cell
      replacement is possible if cells resistant to the toxic environment are employed.
      Furthermore, an important aspect of successful treatment will likely be not only
      cell replacement but also cross-correction of host cells to provide them with
      enzyme activity and hence resistance. While oligodendrocyte replacement alone was
      not a sufficient treatment for GLD (even when extensive), the replacement of both
      cells and molecules -- e.g. with NSCs that could both become oligodendrocytes and
      'pumps' for GalC -- emerges as a promising basis for a multidisciplinary
      strategy. Most neurological disease are complex in this way and will likely
      require multifaceted approaches, perhaps with NSCs serving as the 'glue'.

PMID- 16805771
TI  - Glycine receptors: recent insights into their structural organization and
      functional diversity.
AB  - Strychnine-sensitive glycine receptors (GlyRs) are known to mediate synaptic
      inhibition in spinal cord, brainstem and other regions of the CNS. During the
      past 5 years, considerable progress has been made in delineating structural
      determinants of ligand binding and channel activation in recombinant GlyRs.
      Furthermore, immunohistochemical and gene inactivation studies have disclosed
      distinct distributions and functions of differentially expressed GlyR subtypes in
      retina, hippocampus and the dorsal horn of the spinal cord. Accordingly, GlyRs
      regulate not only the excitability of motor and sensory neurones, but are also
      essential for the processing of photoreceptor signals, neuronal development and
      inflammatory pain sensitization. Hence, these receptors constitute promising
      targets for the development of clinically useful compounds.

PMID- 16805772
TI  - The chemical biology of clinically tolerated NMDA receptor antagonists.
AB  - Most neuroprotective drugs have failed in clinical trials because of side
      effects, causing normal brain function to become compromised. A case in point
      concerns antagonists of the N-methyl-D-aspartate type of glutamate receptor
      (NMDAR). Glutamate receptors are essential to the normal function of the central
      nervous system. However, their excessive activation by excitatory amino acids,
      such as glutamate itself, is thought to contribute to neuronal damage in many
      neurological disorders ranging from acute hypoxic-ischemic brain injury to
      chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's
      disease, Huntington's disease, and amyotrophic lateral sclerosis. The dual role
      of NMDARs in particular for normal and abnormal functioning of the nervous system
      imposes important constraints on possible therapeutic strategies aimed at
      ameliorating neurological diseases. Blockade of excessive NMDAR activity must
      therefore be achieved without interference with its normal function. In general,
      NMDAR antagonists can be categorized pharmacologically according to the site of
      action on the receptor-channel complex. These include drugs acting at the agonist
      (NMDA) or co-agonist (glycine) sites, channel pore, and modulatory sites, such as
      the S-nitrosylation site where nitric oxide (NO) reacts with critical cysteine
      thiol groups. Because glutamate is thought to be the major excitatory transmitter
      in the brain, generalized inhibition of a glutamate receptor subtype like the
      NMDAR causes side-effects that clearly limit the potential for clinical
      applications. Both competitive NMDA and glycine antagonists, even although
      effective in preventing glutamate-mediated neurotoxicity, will cause generalized
      inhibition of NMDAR activities and thus have failed in many clinical trials. Open
      channel block with the property of uncompetitive antagonism is the most appealing
      strategy for therapeutic intervention during excessive NMDAR activation as this
      action of blockade requires prior activation of the receptor. This property, in
      theory, leads to a higher degree of channel blockade in the presence of excessive
      levels of glutamate and little blockade at relatively lower levels, for example,
      during physiological neurotransmission. Utilizing this molecular strategy of
      action, we review here the logical process that we applied over the past decade
      to help develop memantine as the first clinically tolerated yet effective agent
      against NMDAR-mediated neurotoxicity. Phase 3 (final) clinical trials have shown
      that memantine is effective in treating moderate-to-severe Alzheimer's disease
      while being well tolerated. Memantine is also currently in trials for additional
      neurological disorders, including other forms of dementia, glaucoma, and severe
      neuropathic pain. Additionally, taking advantage of memantine's preferential
      binding to open channels and the fact that excessive NMDAR activity can be down
      regulated by S-nitrosylation, we have recently developed combinatorial drugs
      called NitroMemantines. These drugs use memantine as a homing signal to target NO
      to hyperactivated NMDARs in order to avoid systemic side-effects of NO such as
      hypotension (low blood pressure). These second-generation memantine derivatives
      are designed as pathologically activated therapeutics, and in preliminary studies
      appear to have even greater neuroprotective properties than memantine.

PMID- 16805773
TI  - Inositol 1,4,5-trisphosphate IP(3) receptors and their role in neuronal cell
      function.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) receptor is a Ca(2+) release channel
      localized on the endoplasmic reticulum (ER) and plays an important role in
      neuronal function. IP(3) receptor was discovered as a developmentally regulated
      protein missing in the cerebellar mutant mice. Recent studies indicate that
      IP(3)Rs are involved in early development and neuronal plasticity. IP(3) works to
      release IRBIT from the IP(3) binding core in addition to release Ca(2+). IRBIT
      binds to and activates Na, Bicarbonate cotransporter. Electron microscopic study
      show the IP(3) receptor has allosteric property to change its form from square to
      windmill in the presence of Ca(2+). IP(3)R associates with ERp44, a redox sensor,
      Homer, other proteins and is transported as vesicular ER on microtubules. All
      these data suggests IP(3) receptor/CA(2+) channel works as a signaling center
      inside cells.

PMID- 16805774
TI  - Oxidative stress and neurodegeneration: where are we now?
AB  - The brain and nervous system are prone to oxidative stress, and are inadequately
      equipped with antioxidant defense systems to prevent 'ongoing' oxidative damage,
      let alone the extra oxidative damage imposed by the neurodegenerative diseases.
      Indeed, increased oxidative damage, mitochondrial dysfunction, accumulation of
      oxidized aggregated proteins, inflammation, and defects in protein clearance
      constitute complex intertwined pathologies that conspire to kill neurons. After a
      long lag period, therapeutic and other interventions based on a knowledge of
      redox biology are on the horizon for at least some of the neurodegenerative
      diseases.

PMID- 16805775
TI  - The role of mitochondria in inherited neurodegenerative diseases.
AB  - In the past decade, the genetic causes underlying familial forms of many
      neurodegenerative disorders, such as Huntington's disease, Parkinson's disease,
      Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich ataxia, hereditary
      spastic paraplegia, dominant optic atrophy, Charcot-Marie-Tooth type 2A,
      neuropathy ataxia and retinitis pigmentosa, and Leber's hereditary optic atrophy
      have been elucidated. However, the common pathogenic mechanisms of neuronal death
      are still largely unknown. Recently, mitochondrial dysfunction has emerged as a
      potential 'lowest common denominator' linking these disorders. In this review, we
      discuss the body of evidence supporting the role of mitochondria in the
      pathogenesis of hereditary neurodegenerative diseases. We summarize the principal
      features of genetic diseases caused by abnormalities of mitochondrial proteins
      encoded by the mitochondrial or the nuclear genomes. We then address genetic
      diseases where mutant proteins are localized in multiple cell compartments,
      including mitochondria and where mitochondrial defects are likely to be directly
      caused by the mutant proteins. Finally, we describe examples of neurodegenerative
      disorders where mitochondrial dysfunction may be 'secondary' and probably
      concomitant with degenerative events in other cell organelles, but may still play
      an important role in the neuronal decay. Understanding the contribution of
      mitochondrial dysfunction to neurodegeneration and its pathophysiological basis
      will significantly impact our ability to develop more effective therapies for
      neurodegenerative diseases.

PMID- 16805776
TI  - Nitric oxide, cell bioenergetics and neurodegeneration.
AB  - Following stimulation of NMDA receptors, neurons transiently synthesize nitric
      oxide (NO) in a calcium/calmodulin-dependent manner through the activation of
      neuronal NO synthase. Nitric oxide acts as a messenger, activating soluble
      guanylyl cyclase and participating in the transduction signalling pathways
      involving cyclic GMP. Nitric oxide also binds to cytochrome c oxidase, and is
      able to inhibit cell respiration in a process that is reversible and in
      competition with oxygen. This action can also lead to the release of superoxide
      anion from the mitochondrial respiratory chain. Here, we discuss recent evidence
      that this mitochondrial interaction represents a molecular switch for cell
      signalling pathways involved in the control of physiological functions. These
      include superoxide- or oxygen-dependent modulation of gene transcription, calcium
      dependent cell signalling responses, changes in the mitochondrial membrane
      potential or AMP-activated protein kinase-dependent control of glycolysis. In
      pathophysiological conditions, such as brain ischaemia or neurological disorders,
      NO is formed excessively by NMDA receptor over-activation in neurons, or by
      inducible NO synthase from neighbouring glia (microglial cells and astrocytes).
      Elevated NO concentrations can then interact with superoxide anion, generated by
      the mitochondria or by other mechanisms, leading to the formation of the powerful
      oxidant species peroxynitrite. During pathological conditions activation of the
      NAD(+)-consuming enzyme poly(APD-ribose) polymerase-1 (PARP-1) is also a likely
      mechanism for NO-mediated energy failure and neurotoxicity. Activation of PARP-1
      is, however, a repair process, which in milder forms of oxidative stress protects
      neurons from death. Thus, whilst NO plays a physiological role in neuronal cell
      signalling, its over-production may cause neuronal energy compromise leading to
      neurodegeneration.

PMID- 16805777
TI  - The genetics of neurodegenerative diseases.
AB  - In the last 50 years, an enormous amount of progress has been made in dissecting
      the etiology of hereditary neurodegenerative diseases, including the dementias,
      the parkinsonisms, the ataxias and the motor-neuron diseases. In addition, these
      genetic findings are beginning to provide insights into the pathogeneses of the
      sporadic forms of the diseases. Through animal and cellular modeling studies we
      are beginning to gain insights into the pathogenic pathways to disease. This
      mechanistic understanding is now leading to therapeutic strategies based on this
      new understanding. As yet, however, no mechanistic therapies are in use in the
      clinic.

PMID- 16805778
TI  - Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and
      therapeutics.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder characterised by
      the gradual onset of dementia. The pathological hallmarks of the disease are beta
      amyloid (Abeta) plaques, neurofibrillary tangles, synaptic loss and reactive
      gliosis. The current therapeutic effort is directed towards developing drugs that
      reduce Abeta burden or toxicity by inhibiting secretase cleavage, Abeta
      aggregation, Abeta toxicity, Abeta metal interactions or by promoting Abeta
      clearance. A number of clinical trials are currently in progress based on these
      different therapeutic strategies and they should indicate which, if any, of these
      approaches will be efficacious. Current diagnosis of Alzheimer's disease is made
      by clinical, neuropsychologic and neuroimaging assessments. Routine structural
      neuroimaging evaluation with computed tomography and magnetic resonance imaging
      is based on non-specific features such as atrophy, a late feature in the
      progression of the disease, hence the crucial importance of developing new
      approaches for early and specific recognition at the prodromal stages of
      Alzheimer's disease. Functional neuroimaging techniques such as functional
      magnetic resonance imaging, magnetic resonance spectroscopy, positron emission
      tomography and single photon emission computed tomography, possibly in
      conjunction with other related Abeta biomarkers in plasma and CSF, could prove to
      be valuable in the differential diagnosis of Alzheimer's disease, as well as in
      assessing prognosis. With the advent of new therapeutic strategies there is
      increasing interest in the development of magnetic resonance imaging contrast
      agents and positron emission tomography and single photon emission computed
      tomography radioligands that will permit the assessment of Abeta burden in vivo.

PMID- 16805779
TI  - Prion diseases of humans and farm animals: epidemiology, genetics, and
      pathogenesis.
AB  - Neuronal vacuolation (spongiosis), neuronal death, and pronounced glial reactions
      are the hallmarks of transmissible spongiform encephalopathies (TSEs), or prion
      diseases. A wealth of physical, biochemical, and immunological evidence indicates
      that the TSE agent, termed prion, does not contain agent-specific nucleic acid
      encoding its own constituents, as is the case for all other infectious pathogens.
      Also, no adaptive immune responses are elicited upon infection. A defining
      feature of TSEs is the deposition, mainly in the brain and lymphoreticular
      tissues, of an aggregated and structurally abnormal protein, designated PrP(Sc)
      or PrP-res, which represents a conformational isomer of the ubiquitous surface
      protein PrP(C). Biochemical and genetic evidence link PrP and its gene to the
      disease. Although TSEs are by definition transmissible, a growing number of Prnp
      associated non-infectious neurodegenerative proteinopathies are now being
      recognized.

PMID- 16805780
TI  - Gene-environment interactions in sporadic Parkinson's disease.
AB  - Much has been learned in recent years about the genetics of familial Parkinson's
      disease. However, far less is known about those malfunctioning genes which
      contribute to the emergence and/or progression of the vast majority of cases, the
      'sporadic Parkinson's disease', which is the focus of our current review. Drastic
      differences in the reported prevalence of Parkinson's disease in different
      continents and countries suggest ethnic and/or environmental-associated
      multigenic contributions to this disease. Numerous association studies showing
      variable involvement of multiple tested genes in these distinct locations support
      this notion. Also, variable increases in the risk of Parkinson's disease due to
      exposure to agricultural insecticides indicate complex gene-environment
      interactions, especially when genes involved in protection from oxidative stress
      are explored. Further consideration of the brain regions damaged in Parkinson's
      disease points at the age-vulnerable cholinergic-dopaminergic balance as being
      involved in the emergence of sporadic Parkinson's disease in general and in the
      exposure-induced risks in particular. More specifically, the chromosome 7
      ACHE/PON1 locus emerges as a key region controlling this sensitive balance, and
      animal model experiments are compatible with this concept. Future progress in the
      understanding of the genetics of sporadic Parkinson's disease depends on globally
      coordinated, multileveled studies of gene-environment interactions.

PMID- 16805781
TI  - Relationship between efficiency and pedal rate in cycling: significance of
      internal power and muscle fiber type composition.
AB  - Cycling was performed to test the following two hypotheses: (1) muscular
      efficiency is unrelated to pedal rate (61, 88, and 115 r.p.m.) for a group of
      subjects with a wide range of slow twitch (ST) fibers in spite of decreasing
      whole-body efficiency and (2) muscular efficiency correlates positively with % ST
      muscle fibers, and this correlation is more pronounced at low pedal rates than at
      high pedal rates. Whole-body gross efficiency decreased from 20-22% at 61 r.p.m.
      to 15-18% at 115 r.p.m. Mean muscular efficiency for all subjects (n=16) was
      approximately 26%, with delta efficiency being constant and muscular efficiency
      (taking internal power into account) slightly increasing with pedal rate.
      Muscular efficiency correlated positively (R(2)=0.25) with % ST fibers (21-97% ST
      in m. vastus lateralis) at 115 r.p.m. while not at 61 and 88 r.p.m. In
      conclusion, the decrease in whole-body gross efficiency with increasing pedal
      rate was not explained by a decrease in muscular efficiency, and supported
      increase in internal power to account for the increase in metabolic power with
      increasing pedal rate. Furthermore, differences between individuals in muscle
      fiber type composition affected muscular efficiency, which correlated positively
      with % ST muscle fibers during fast pedalling.

PMID- 16805782
TI  - Anatomy of the anterior cruciate ligament double bundle structure: a macroscopic
      evaluation.
AB  - INTRODUCTION: Traditional anterior cruciate ligament (ACL) surgery has
      demonstrated good results, but there is still a subset of unsatisfactory
      outcomes. Trends in reconstruction technique have changed from bone-patella
      tendon-bone to hamstring refixation, and the next step appears to be the double
      bundle concept. METHODS: We examined six fresh-frozen cadaver knees to evaluate
      the double bundle structure, dynamic motion characteristics and the relationship
      of knee flexion and relative position of the femoral insertion sites of the ACL.
      RESULTS: In all knees, we identified an anteromedial (AM) and posterolateral (PL)
      bundle. The motion pattern demonstrated that the AM and PL bundles are oriented
      near parallel with the knee extended, and twist around each other as the knee is
      flexed. The visualization of the femoral footprint anatomy differs with knee
      flexion. DISCUSSION: The double bundle model facilitates restoration of the
      original footprint anatomy and biomechanics more easily than the concept of the
      ACL as a one-bundle structure and the use of the o'clock position. It is
      essential to be aware of the degree of knee flexion when drilling the femoral
      tunnels. PERSPECTIVE: Anatomic ACL reconstruction is a concept, not a technique,
      and allows a more refined surgical approach to ACL reconstruction including
      revision cases and partial ACL tears.

PMID- 16805783
TI  - Moderate exercise in hypoxia induces a greater arterial desaturation in trained
      than untrained men.
AB  - During moderate exercise breathing a low inspired O(2) fraction (F(I)O(2)),
      arterial O(2) desaturation may depend on the fitness level. Seven trained (TM)
      and seven untrained men (UTM) cycled in normoxia and in hypoxia (F(I)O(2)=0.187,
      0.173, 0.154, 0.13 and 0.117). We compared TM and UTM at submaximal intensities
      below the ventilatory threshold. Ventilatory variables were monitored and
      arterial oxygen saturation was measured by pulse oximetry. O(2) saturation was
      not different between groups at sea level. In hypoxia, O(2) saturation was lower
      in TM than in UTM at F(I)O(2)=0.154 (87.3 +/- 2.9% vs 90.4 +/- 1.5% at 90 W) and
      below. Both the ventilatory-equivalent and the end-tidal O(2) pressure were lower
      in TM at sea level and at every F(I)O(2), with the differences between TM and UTM
      becoming apparent at lower exercise intensity and increasing in magnitude as the
      severity of hypoxia increased. O(2) saturation was correlated with the
      ventilatory parameters at every F(I)O(2) and the correlations were stronger in
      severe hypoxia. These results demonstrate that a moderate exercise carried out in
      hypoxia, contrary to normoxic conditions, can lead to a greater arterial
      desaturation in TM compared with UTM. This phenomenon could be partly attributed
      to a relative hypoventilation in trained subjects.

PMID- 16805784
TI  - Gamma loop dysfunction in the quadriceps femoris of patients who underwent
      anterior cruciate ligament reconstruction remains bilaterally.
AB  - Purpose of this study was to investigate the effects of anterior cruciate
      ligament (ACL) repair on the gamma loop of the bilateral quadriceps femoris (QF).
      Maximal voluntary contraction (MVC) of knee extension and integrated
      electromyogram (I-EMG) of vastus medialis (VM), vastus lateralis (VL), and rectus
      femoris (RF) were examined in uninjured and injured limbs of 18 patients and 10
      normal subjects, before and after 20-min vibration applied to the QF. Mean
      percentage changes were calculated as: (pre-vibration value-post-vibration
      value)/pre-vibration value x 100. Patients were divided into two groups: short
      term-group (tested </=12 months after ACL repair, n=8), long-term-group (tested
      >/=18 months after ACL repair, n=10). Mean percentage changes of the four groups
      were compared with those of controls. Results indicated that changes of MVC and I
      EMG on the uninjured and injured sides in short-term-group in response to
      vibration were significantly different from those of controls. There were no
      significant differences between uninjured sides in long-term and control groups.
      MVC and I-EMG of VM and RF of injured side in patients in the long-term-group in
      response to vibration were not different from those of controls. From these
      results, we concluded that this abnormality of the gamma loop in both injured and
      uninjured sides did not recover despite ACL reconstruction. However, the
      abnormality in uninjured side might recover >/=18 months after repair.

PMID- 16805785
TI  - Swimmers' painful shoulder arthroscopic findings and return rate to sports.
AB  - Shoulder pain is the most common musculo-skeletal complaint in competitive
      swimmers. It remains one of the shoulder pain syndromes in overhead athletes
      where no golden standard of treatment exists. Eighteen competitive swimmers who
      all had undergone shoulder arthroscopy for therapy-resistant shoulder pain were
      retrospectively evaluated with respect to operative findings and ability to
      return to their sport after the operation. The most common finding at arthroscopy
      was labral pathology in 11 (61%) and subacromial impingement in five shoulders
      (28%). Operative procedures included debridement in 11 swimmers, partial release
      of the coraco-acromial ligament in four, and bursectomy in four. Sixteen (89%)
      responded to the follow-up evaluation. Nine swimmers (56%) were able to compete
      at preinjury level after 4 (2-9) months. Findings at arthroscopy suggest that the
      term "Swimmer's shoulder" covers a variety of pathologies including labral
      wearing and subacromial impingement. Arthroscopic debridement of labral tears or
      bursectomy in swimmers with shoulder pain has a low success rate with regard to
      return to sport. Further understanding and investigation of this syndromes
      complex pathophysiology is needed.

PMID- 16805786
TI  - Decreased intramuscular blood flow in patients with lateral epicondylitis.
AB  - The purpose of this pilot study was to investigate intramuscular microcirculation
      in extensor carpi radialis brevis (ECRB) in patients with lateral epicondylitis.
      Ten patients with unilateral epicondylitis, mean duration of symptoms of 39 (12
      96) months participated. The diagnosis was based on clinical examination and none
      was under treatment for the last 6 months. Isometric handgrip strength, 2-pinch
      grip strength and muscle strength during radial deviation and dorsal extension
      were determined. Functional perceived pain was evaluated by a modified behaviour
      rating scale and perceived pain during contraction by visual analogue scale.
      Intramuscular and skin blood flow was recorded by a laser-Doppler flowmetry
      system technique (LDF) during stable temperature condition. Intramuscular blood
      flow was significantly lower in the affected side, 22.7+/-9.8 perfusion units
      (PU), as compared with 35.2+/-11.9 PU in the control side (P=0.01). There was no
      difference in skin blood flow or temperature between the affected and the control
      side. A positive correlation was found between the duration of symptoms and the
      difference in intramuscular blood flow between the affected and the control arm
      (r=0.65, P=0.06). The present data indicate that decreased microcirculation and
      anaerobic metabolism in ECRB may contribute to the lateral epicondylitis
      symptoms.

PMID- 16805787
TI  - Correction of penile curvature by rotation of the corpora cavernosa: a case
      report.
AB  - AIM: We report on the corporal rotation technique, customized for the management
      of ventral curvature in patients without hypospadias. METHODS: A male patient
      with ventral curvature of 90 degrees was operated on. The neurovascular bundle
      was mobilized for a short distance at the point of maximum curvature. The corpora
      cavernosa were approximated to each other in the dorsal midline by suturing pairs
      of longitudinal parallel incisions. To avoid urethral narrowing, minimal
      dissection was used to develop the groove on either side of the corpus
      spongiosum, to release it from its attachment to the rotated corpora cavernosa.
      RESULTS: Full correction of the curvature was achieved, without shortening,
      erectile dysfunction, or micturition problems. CONCLUSION: Corporal rotation can
      be applied for the correction of ventral penile curvature in patients with and
      without hypospadias, without sacrificing penile length.

PMID- 16805788
TI  - Enhancement of CD8 T-cell function through modifying surface glycoproteins in
      young and old mice.
AB  - Previous work from our laboratory has shown that modifying cell surface
      glycosylation with either a Clostridium perfringens-derived sialidase (CP-Siase),
      or an O-linked glycoprotein endopeptidase (OSGE) can enhance the function of CD4
      T cells from both young and old mice at multiple levels. Here we have re-assessed
      the effect of age on CD8 T-cell function, and examined the outcome of enzymatic
      treatment with CP-Siase and OSGE on its different aspects. Pre-treatment of CD8 T
      cells with either CP-Siase or OSGE led to a significant increase in anti-CD3
      mediated Ca2+ response in both young and old mice. Pre-treated CD8 T cells from
      both age groups also displayed a significant increase in activation-induced CD69
      and CD25 expression, and produced significantly higher amounts of interleukin-2
      and interferon-gamma in comparison to their untreated counterparts. Furthermore,
      pretreatment with either enzyme enhanced granzyme B expression in CD8 T cells,
      and increased their cytolytic activity in vitro. These data support the notion
      that glycosylated surface proteins hinder CD8 T-cell activation and function in
      both young and old mice, and raise the possibility of significantly improving CD8
      T cell function in older individuals through enzymatic alteration of surface
      glycoproteins.

PMID- 16805789
TI  - CD43-independent augmentation of mouse T-cell function by glycoprotein cleaving
      enzymes.
AB  - Previous work has shown that the function of mouse CD4+ T cells can be augmented
      by an enzyme, O-sialoglycoprotein endopeptidase (OSGE), which cleaves surface
      CD43, suggesting the idea that the high levels of glycosylated CD43 found on T
      cells from aged mice may contribute to immune senescence. New results now show
      that OSGE improves T-cell function even in mice lacking CD43, showing that other
      glycoproteins must contribute to the OSGE effect on function. Evaluation of other
      enzymes found two whose ability to stimulate CD4 activation was higher in aged
      than in young T cells. One of these, PNGase F, is a glycosidase specific for N
      linked glycans, and the other, ST-Siase(2,3) from Salmonella typhimurium, is
      specific for alpha2,3-linked terminal sialic acid residues. Parallel lectin
      binding experiments showed that removal of alpha2,3-linked sialic acid residues
      vulnerable to PNGase F and ST-Siase(2,3) was also greater in old than in young T
      cells. The preferential ability of PNGase F and ST-Siase(2,3) to improve the
      function of T cells from aged mice may involve cleavage of glycoproteins
      containing alpha2,3-linked sialic acid residues on N-linked or O-linked glycans
      or both.

PMID- 16805790
TI  - A variable number of tandem repeats polymorphism influences the transcriptional
      activity of the neonatal Fc receptor alpha-chain promoter.
AB  - The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG)
      transport across placental barriers. Genetic variations of FcRn-dependent
      transport across the placenta may influence antibody-mediated pathologies of the
      fetus and the newborn. Sequencing analysis of 20 unrelated individuals
      demonstrated no missense mutation within the five exons of the FcRn gene.
      However, a variable number of tandem repeats (VNTR) region within the FcRn
      promoter was observed, consisting of five different alleles (VNTR1-VNTR5).
      Alleles with two (VNTR2) and three (VNTR3) repeats were found to be most common
      in Caucasians (7.5 and 92.0%, respectively). Real-time polymerase chain reaction
      revealed that monocytes from VNTR3 homozygous individuals express 1.66-fold more
      FcRn transcript than do monocytes from VNTR2/VNTR3 heterozygous individuals (P =
      0.002). In reporter plasmid assays, the VNTR3 allele supported the transcription
      of a reporter gene twice as effectively as did the VNTR2 allele (P = 0.003).
      Finally, under acidic conditions, monocytes from VNTR3 homozygous individuals
      showed an increased binding to polyvalent human IgG when compared with monocytes
      from VNTR2/VNTR3 heterozygous individuals (P = 0.021). These data indicate that a
      VNTR promoter polymorphism influences the expression of the FcRn receptor,
      leading to different IgG-binding capacities.

PMID- 16805791
TI  - Interaction between ephrins/Eph receptors and excitatory amino acid receptors:
      possible relevance in the regulation of synaptic plasticity and in the
      pathophysiology of neuronal degeneration.
AB  - There is increasing evidence that Eph receptors and their transmembrane ligands,
      named ephrins, interact with glutamate receptors in both developing and adult
      neurons. EphB receptors interact with proteins that regulate the membrane
      trafficking of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)
      receptor subunits, and both ephrins and EphB receptors have been found to co
      localize with N-methyl-d-aspartate (NMDA) receptors and to positively modulate
      NMDA receptor function. Moreover, pharmacologic activation of ephrin-Bs amplifies
      group-I metabotropic glutamate receptor signaling through mechanisms that involve
      NMDA receptors. The interaction with ionotropic or metabotropic glutamate
      receptors provides a substrate for the emerging role of ephrins and Eph receptors
      in the regulation of activity-dependent forms of synaptic plasticity, such as
      long-term potentiation and long-term depression, which are established
      electrophysiologic models of associative learning. In addition, these
      interactions explain the involvement of ephrins/Eph receptors in the regulation
      of pain threshold and epileptogenesis, as well as their potential implication in
      processes of neuronal degeneration. This may stimulate the search for new drugs
      that might modulate excitatory synaptic transmission by interacting with the
      ephrin/Eph receptor system.

PMID- 16805792
TI  - Quiescence induced by iron challenge protects neuroblastoma cells from oxidative
      stress.
AB  - The brain uses massive amounts of oxygen, generating large quantities of reactive
      oxygen species (ROS). Because of its lipid composition, rich in unsaturated fatty
      acids, the brain is especially vulnerable to ROS. Furthermore, oxidative damage
      in the brain is often associated with iron, which has pro-oxidative properties.
      Iron-mediated oxidative damage in the brain is compounded by the fact that brain
      iron distribution is non-uniform, being particularly high in areas sensitive to
      neurodegeneration. This work was aimed to further our understanding of the
      cellular mechanisms by which SHSY5Y neuroblastoma cells adapt to, and survive
      increasing iron loads. Using an iron accumulation protocol that kills about 50%
      of the cell population, we found by cell sorting analysis that the SHSY5Y sub
      population that survived the iron loading arrested in the G(0) phase of the cell
      cycle. These cells expressed neuronal markers, while their electrical properties
      remained largely unaltered. These results suggest that upon iron challenge,
      neuroblastoma cells respond by entering the G(0) phase, somehow rendering them
      resistant to oxidative stress. A similar physiological condition might be
      involved in neuronal survival in tissues known to accumulate iron with age, such
      as the hippocampus and the substantia nigra pars compacta.

PMID- 16805793
TI  - Enhancement of insulin-induced PI3K/Akt/GSK-3beta and ERK signaling by neuronal
      nicotinic receptor/PKC-alpha/ERK pathway: up-regulation of IRS-1/-2 mRNA and
      protein in adrenal chromaffin cells.
AB  - In cultured bovine adrenal chromaffin cells treated with nicotine (10 microm for
      24 h), phosphorylation of Akt, glycogen synthase kinase-3beta (GSK-3beta) and
      extracellular signal-regulated kinase (ERK)1/2 induced by insulin (100 nm for 10
      min) was enhanced by approximately 62%, without altering levels of these protein
      kinases. Nicotine produced time (> 12 h)- and concentration (EC(50) 3.6 and 13
      microm)-dependent increases in insulin receptor substrate (IRS)-1 and IRS-2
      levels by approximately 125 and 105%, without altering cell surface density of
      insulin receptors. In these cells, insulin-induced tyrosine phosphorylation of
      IRS-1/IRS-2 and recruitment of phosphoinositide 3-kinase (PI3K) to IRS-1/IRS-2
      were augmented by approximately 63%. The increase in IRS-1/IRS-2 levels induced
      by nicotine was prevented by nicotinic acetylcholine receptor (nAChR)
      antagonists, the Ca(2+) chelator 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra
      acetic acid tetrakis-acetoxymethyl ester, cycloheximide or actinomycin D.
      Nicotine increased IRS-1 and IRS-2 mRNA levels by approximately 57 and
      approximately 50%, and this was prevented by conventional protein kinase C (cPKC)
      inhibitor Go6976, or ERK kinase inhibitors PD98059 and U0126. Nicotine
      phosphorylated cPKC-alpha, thereby increasing phosphorylation of ERK1/ERK2, as
      demonstrated by using Go6976, PD98059 or U0126. Selective activation of cPKC
      alpha by thymeleatoxin mimicked these effects of nicotine. Thus, stimulation of
      nAChRs up-regulated expression of IRS-1/IRS-2 via Ca(2+)-dependent sequential
      activation of cPKC-alpha and ERK, and enhanced insulin-induced PI3K/Akt/GSK-3beta
      and ERK signaling pathways.

PMID- 16805794
TI  - Tomoregulin-2 is found extensively in plaques in Alzheimer's disease brain.
AB  - Tomoregulin (TR)2 is a transmembrane protein predominantly expressed in brain. It
      has a unique extracellular domain, containing epidermal growth factor-like and
      follistatin-like modules. The ectodomain is released from the cell surface, and
      thought to function as a neurotrophic factor and dendritogenic agent. During CNS
      development and in the neuronal storage disease GM2 gangliosidosis, which is
      characterized by ectopic dendrites, the TR2 ectodomain is present in neuronal
      nuclei where it may function in dendrite initiation. Data presented here
      demonstrate that TR2 is found extensively in Alzheimer's disease (AD) plaques.
      Confocal microscopy shows that TR2 is present throughout plaques. Interestingly,
      TR2 is absent from plaques in the presenilin-1/amyloid precursor protein mouse
      model of AD. From these data, and what is known about TR2, it is hypothesized
      that TR2 may participate in amyloid plaque formation and contribute to the
      pathogenesis of AD. The human TR2 gene is located on chromosome 2q32.3, near a
      locus linked to Parkinson's disease. TR2 is reported to be a trophic factor for
      dopaminergic mesencephalic neurons.

PMID- 16805795
TI  - Embryonic stem cell-derived neuron models of Parkinson's disease exhibit delayed
      neuronal death.
AB  - Establishment of a Parkinson's disease (PD) neuron model was attempted with mouse
      embryonic stem (ES) cells. ES cell lines over-expressing mouse nuclear receptor
      related 1 (Nurr1), together with human wild-type and alanine 30 --> proline
      (A30P) and alanine 53 --> threonine (A53T) mutant alpha-synuclein were
      established and subjected to differentiation into dopaminergic neurons. The ES
      cell-derived dopaminergic neurons expressing wild-type or mutant alpha-synuclein
      exhibited the fundamental characteristics consistent with dopaminergic neurons in
      the substantia nigra. The ES cell-derived PD model neurons exhibited increased
      susceptibility to oxidative stress, proteasome inhibition, and mitochondrial
      inhibition. Cell viability of PD model neurons and the control neurons was
      similar until 28 days after differentiation. Nonetheless, after that time, PD
      model neurons gradually began to undergo neuronal death over the course of 1
      month, showing cytoplasmic aggregate formation and an increase of insoluble alpha
      synuclein protein. Such delayed neuronal death was observed in a mutant alpha
      synuclein protein level-dependent manner, which was slightly inhibited by a c-jun
      N-terminal kinase inhibitor and a caspase inhibitor. Such cell death was not
      observed when the same ES cell lines were differentiated into oligodendrocytes.
      The ES cell-derived PD model neurons are considered as prospective candidates for
      a new prototype modelling PD that would allow better investigation of the
      underlying neurodegenerative pathophysiology.

PMID- 16805796
TI  - A novel tricyclic pyrone compound ameliorates cell death associated with
      intracellular amyloid-beta oligomeric complexes.
AB  - The neurotoxicity of amyloid-beta protein (Abeta) is widely regarded as one of
      the fundamental causes of neurodegeneration in Alzheimer's disease (AD). This
      toxicity is related to Abeta aggregation into oligomers, protofibrils and
      fibrils. Recent studies suggest that intracellular Abeta, which causes profound
      toxicity, could be one of the primary therapeutic targets in AD. So far, no
      compounds targeting intracellular Abeta have been identified. We have
      investigated the toxicity induced by intracellular Abeta in a neuroblastoma MC65
      line and found that it was closely related to intracellular accumulation of
      oligomeric complexes of Abeta (Abeta-OCs). We further identified a cell-permeable
      tricyclic pyrone named CP2 that ameliorates this toxicity and significantly
      reduces the levels of Abeta-OCs. In aqueous solution, CP2 attenuates Abeta
      oligomerization and prevents the oligomer-induced death of primary cortical
      neurons. CP2 analogs represent a new class of promising compounds for the
      amelioration of Abeta toxicities within both intracellular and extracellular
      sites.

PMID- 16805797
TI  - Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co
      expressed in a subset of taste receptor cells.
AB  - Taste receptors cells are responsible for detecting a wide variety of chemical
      stimuli. Several molecules including both G protein coupled receptors and ion
      channels have been shown to be involved in the detection and transduction of
      tastants. We report on the expression of two members of the transient receptor
      potential (TRP) family of ion channels, PKD1L3 and PKD2L1, in taste receptor
      cells. Both of these channels belong to the larger polycystic kidney disease (PKD
      or TRPP) subfamily of TRP channels, members of which have been demonstrated to be
      non-selective cation channels and permeable to both Na(+) and Ca(2+). Pkd1l3 and
      Pkd2l1 are co-expressed in a select subset of taste receptor cells and therefore
      may, like other PKD channels, function as a heteromer. We found the taste
      receptor cells expressing Pkd1l3 and Pkd2l1 to be distinct from those that
      express components of sweet, bitter and umami signal transduction pathways. These
      results provide the first evidence for a role of TRPP channels in taste receptor
      cell function.

PMID- 16805798
TI  - Proteolytic cleavage of the neural cell adhesion molecule by ADAM17/TACE is
      involved in neurite outgrowth.
AB  - The transmembrane and multidomain neural cell adhesion molecule (NCAM) plays
      important functional roles in the developing and adult nervous system. NCAM is
      proteolytically processed and appears in soluble forms in the cerebrospinal fluid
      and in serum under normal and pathological conditions. In this report, we present
      evidence that the metalloprotease a disintegrin and a metalloprotease
      (ADAM)17/tumour necrosis factor alpha converting enzyme (TACE) cleaves the
      polysialylated as well as the non-polysialylated transmembrane isoforms of NCAM,
      whereas the glycophosphatidylinositol-linked isoform of NCAM is not
      proteolytically cleaved. A truncated, enzymatically inactive mutant of TACE did
      not result in release of the NCAM110 cleavage product. Proteolytic cleavage was
      enhanced by a calmodulin-specific inhibitor and the actin-destabilizing agents
      cytochalasin D and latrunculin B. In contrast, the microtubule-stabilizing agent
      colchicine or microtubule-destabilizing agent paclitaxel did not affect the
      release of the 110-kDa fragment of NCAM. Neurite outgrowth from cerebellar
      microexplants was inhibited in the presence of the metalloprotease inhibitor GM
      6001 on substrate-coated NCAM, but not on poly-l-lysine. Upon transfection of
      hippocampal neurones with an enzymatically inactive mutant of TACE, NCAM
      stimulated neurite outgrowth was inhibited without affecting neurite outgrowth on
      poly-l-lysine, showing that proteolytic processing of NCAM by the metalloprotease
      TACE is involved in NCAM-mediated neurite outgrowth.

PMID- 16805799
TI  - Biochemical and biological characterization of a neuroendocrine-associated
      phosphatase.
AB  - The biochemical and biological properties of a novel neuroendocrine-associated
      phosphatase (NEAP) were characterized. NEAP had a sequence characteristic of a
      dual-specificity phosphatase (DSP), and was preferentially expressed in
      neuroendocrine cells/tissues as well as in skeletal muscle and heart. Expression
      of NEAP was up-regulated in nerve growth factor (NGF)-treated, differentiated
      PC12 cells. NEAP was cytosolic and did not apparently have effects against
      extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK) and p38
      mitogen-activated protein kinase activated by various stimuli. Although NEAP and
      MAPK phosphatase (MPK)-1 showed similar phosphatase activity towards p-nitro
      phenylphosphate (pNPP), in contrast to MKP-1, NEAP did not dephosphorylate JNK
      and p38-MAPK in vitro. Overexpression of NEAP, but not the C152S mutant, in PC12
      cells suppressed NGF-induced phosphorylation of the p85 subunit of
      phosphatidylinositol 3-kinase (PI3K) and Akt activation. Overexpression of NEAP
      also suppressed neurite outgrowth induced by NGF and sensitized PC12 cells to
      cisplatin-induced apoptosis. Suppression of NEAP by RNA interference enhanced NGF
      induced neurite outgrowth and Akt activation. Our results indicated that, unlike
      other DSPs, down-regulation of conventional MAPKs was not the major function of
      NEAP. Furthermore, NEAP might be involved in neuronal differentiation via
      regulation of the PI3K/Akt signaling.

PMID- 16805801
TI  - Differential alpha-mediated inhibition of dopamine and noradrenaline release in
      the parietal and occipital cortex following noradrenaline transporter blockade.
AB  - Parietal and occipital cortices, while densely innervated by noradrenalin 2 (NA)
      projections, possess a comparatively sparse dopamine 2 (DA) innervation, even
      sparser than the prefrontal cortex. We previously reported that reboxetine and
      desipramine, two selective norepinephrine transporter (NET) blockers, at doses
      that maximally increase DA in the prefrontal cortex, do not increase DA in the
      parietal and occipital cortices. In the present study, we performed a full dose
      response study of the effect of systemic reboxetine and desipramine on DA and NA
      in dialysates from the parietal and occipital cortices. Seven doses of reboxetine
      (0.1, 0.25, 0.5, 1.0, 2.5, 5.0 and 10 mg/kg) and four doses of desipramine (0.25,
      1.0, 2.5 and 5.0 mg/kg) were tested. Reboxetine and desipramine differentially
      affected dialysate DA as compared with NA. Reboxetine increased DA maximally by
      about 100% after doses of 0.25-0.5 mg/kg and showed a bell-shaped dose-response
      function in both areas; desipramine did not affect DA in the parietal cortex and
      increased it in the occipital cortex only at 2.5 mg/kg. NA was maximally
      increased by 275% by 0.5-2.5 mg/kg reboxetine and by about 300% by 5.0 mg/kg
      desipramine with a more linear dose-response curve. The mechanism of peculiar
      dose-response function of dialysate DA after reboxetine and desipramine was
      further investigated by testing the effect of drugs on dialysate DA and NA under
      alpha(2) receptor blockade. Under local perfusion of the occipital cortex with
      idazoxan, an otherwise ineffective dose of reboxetine and desipramine (5 mg/kg)
      became effective in raising extracellular DA. In contrast, the effect of
      reboxetine on NA was potentiated, while that of desipramine was not affected.
      These results suggest that, in the parietal and occipital cortices, extracellular
      NA, raised by NET blockade, exerts a preferential inhibitory influence on DA
      release by acting on local alpha(2) receptors, thus accounting for the bell
      shaped feature of the dose-response function of drugs on dialysate DA in these
      areas.

PMID- 16805800
TI  - Irreversible aggregation of protein synthesis machinery after focal brain
      ischemia.
AB  - Focal brain ischemia leads to a slow type of neuronal death in the penumbra that
      starts several hours after ischemia and continues to mature for days. During this
      maturation period, blood flow, cellular ATP and ionic homeostasis are gradually
      recovered in the penumbral region. In striking contrast, protein synthesis is
      irreversibly inhibited. This study used a rat focal brain ischemia model to
      investigate whether or not irreversible translational inhibition is due to
      abnormal aggregation of translational complex components, i.e. the ribosomes and
      their associated nascent polypeptides, protein synthesis initiation factors and
      co-translational chaperones. Under electron microscopy, most rosette-shaped
      polyribosomes were relatively evenly distributed in the cytoplasm of sham
      operated control neurons, but clumped into large abnormal aggregates in penumbral
      neurons subjected to 2 h of focal ischemia followed by 4 h of reperfusion. The
      abnormal ribosomal protein aggregation lasted until the onset of delayed neuronal
      death at 24-48 h of reperfusion after ischemia. Biochemical study further
      suggested that translational complex components, including small ribosomal
      subunit protein 6 (S6), large subunit protein 28 (L28), eukaryotic initiation
      factors 2alpha, 4E and 3eta, and co-translational chaperone heat-shock cognate
      protein 70 (HSC70) and co-chaperone Hdj1, were all irreversibly clumped into
      large abnormal protein aggregates after ischemia. Translational complex
      components were also highly ubiquitinated. This study clearly demonstrates that
      focal ischemia leads to irreversible aggregation of protein synthesis machinery
      that contributes to neuronal death after focal brain ischemia.

PMID- 16805802
TI  - Social isolation-induced increase in alpha and delta subunit gene expression is
      associated with a greater efficacy of ethanol on steroidogenesis and GABA
      receptor function.
AB  - Previously we have demonstrated that social isolation of rats reduces both the
      cerebrocortical and plasma concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one
      (3alpha,5alpha-TH PROG), and potentiates the positive effects of acute ethanol
      administration on the concentrations of this neurosteroid. We now show that the
      ethanol-induced increase in 3alpha,5alpha-TH PROG is more pronounced in the brain
      than in the plasma of isolated rats. The ability of ethanol to inhibit isoniazid
      induced convulsions is greater in isolated rats than in group-housed animals and
      this effect is prevented by treatment with finasteride. Social isolation modified
      the effects of ethanol on the amounts of steroidogenic regulatory protein mRNA
      and protein in the brain. Moreover, ethanol increased the amplitude of GABA(A)
      receptor-mediated miniature inhibitory postsynaptic currents recorded from CA1
      pyramidal neurones with greater potency in hippocampal slices prepared from
      socially isolated rats than in those from group-housed rats, an effect inhibited
      by finasteride. The amounts of the alpha(4) and delta subunits of the GABA(A)
      receptor in the hippocampus were increased in isolated rats as were GABA(A)
      receptor-mediated tonic inhibitory currents in granule cells of the dentate
      gyrus. These results suggest that social isolation results in changes in GABA(A)
      receptor expression in the brain, and in an enhancement of the stimulatory effect
      of ethanol on brain steroidogenesis, GABA(A) receptor function and associated
      behaviour.

PMID- 16805803
TI  - WAY-100635 antagonist-induced plasticity of 5-HT receptors: regulatory
      differences between a stable cell line and an in vivo native system.
AB  - We present evidence that the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor
      antagonist, N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl}-N-(2
      pyridinyl)cyclohexanecarboxamide (WAY-100635), can induce receptor
      internalization in a human (h)5-HT(1A) receptor Chinese hamster ovary (CHO-K1)
      cell system. Exposure of h5-HT(1A) CHO cells to WAY-100635 decreased the cell
      surface h5-HT(1A) receptor density in a way that was both time (24-72 h) and
      concentration (1-100 nm) dependent.[(3)H]WAY-100635 and [(3)H]8-hydroxy
      dipropylaminotetralin ([(3)H]8-OH-DPAT) saturation analyses demonstrated a
      significant reduction (50-60%) in total h5-HT(1A) receptor number in the WAY
      100635-treated (100 nm; 72 h) compared with control cells. In WAY-100635-treated
      cells, the 8-OH-DPAT-mediated inhibition of forskolin (FSK)-stimulated cAMP
      accumulation was right-shifted and the maximal inhibitory response of 8-OH-DPAT
      was impaired compared with control cells. Similar results were obtained for 8-OH
      DPAT-mediated Ca(2+) mobilization after WAY-100635 treatment. h5-HT(1A) receptors
      labeled with [(3)H]WAY-100635, as well as [(3)H]4-(2'-Methoxy)-phenyl-1-[2'-(N
      2''-pyridinyl)-p-fluorobenzamido]ethyl-piperazine (MPPF), exhibited a time
      dependent rate of cellular internalization that was blocked by endocytotic
      suppressors and was pertussis-toxin insensitive. In contrast, quantitative
      autoradiographic studies demonstrated that chronic treatment of rats with WAY
      100635 for two weeks produced a region-specific increase in the 5-HT(1A) receptor
      density. In conclusion, prolonged exposure of an h5-HT(1A) cell-based system to
      the 5-HT(1A) antagonist, WAY-100635, induced a paradoxical internalization of
      cell surface receptor resulting in depressed functional activity. This suggests
      that an antagonist can influence 5-HT(1A) receptor recycling in vitro differently
      to in vivo regulatory conditions.

PMID- 16805804
TI  - The immunophilin ligand GPI1046 protects neurons from the lethal effects of the
      HIV-1 proteins gp120 and Tat by modulating endoplasmic reticulum calcium load.
AB  - The dysfunction and death of neuronal cells is thought to underlie the cognitive
      manifestations of human immunodeficiency virus (HIV)-associated neurological
      disorders. Although HIV-infected patients are living longer owing to the
      effectiveness of anti-retroviral therapies, the number of patients developing
      neurological disorders is on the rise. Thus, there is an escalating need for
      effective therapies to preserve cognitive function in HIV-infected patients.
      Using HIV-protein-induced neurotoxicity as a model system, we tested the
      effectiveness of a non-immunosuppressive immunophilin ligand to attenuate gp120
      and Tat-induced modification of neuronal function. The immunophilin ligand
      GPI1046 attenuated endoplasmic reticulum (ER) calcium release induced by gp120
      and Tat and protected neurons from the lethal effect of these neurotoxic HIV
      proteins. Both inositol 1,4,5 trisphosphate (IP(3)) and ryanodine-sensitive ER
      calcium release was attenuated by pre-incubation with GPI1046. Using the
      sarco/endoplasmic reticulum calcium pump inhibitor thapsigargin to release ER
      calcium, we determined that GPI1046 reduced the total ER calcium load. These
      findings suggest that non-immunosuppressive immunophilin ligands may be useful
      neuroprotective drugs in HIV dementia.

PMID- 16805805
TI  - Altered cleavage and localization of PINK1 to aggresomes in the presence of
      proteasomal stress.
AB  - Following our identification of PTEN-induced putative kinase 1 (PINK1) gene
      mutations in PARK6-linked Parkinson's disease (PD), we have recently reported
      that PINK1 protein localizes to Lewy bodies (LBs) in PD brains. We have used a
      cellular model system of LBs, namely induction of aggresomes, to determine how a
      mitochondrial protein, such as PINK1, can localize to aggregates. Using specific
      polyclonal antibodies, we firstly demonstrated that human PINK1 was cleaved and
      localized to mitochondria. We demonstrated that, on proteasome inhibition with MG
      132, PINK1 and other mitochondrial proteins localized to aggresomes.
      Ultrastructural studies revealed that the mechanism was linked to the recruitment
      of intact mitochondria to the aggresome. Fractionation studies of lysates showed
      that PINK1 cleavage was enhanced by proteasomal stress in vitro and correlated
      with increased expression of the processed PINK1 protein in PD brain. These
      observations provide valuable insights into the mechanisms of LB formation in PD
      that should lead to a better understanding of PD pathogenesis.

PMID- 16805806
TI  - Blockade of the translocation and activation of mitogen-activated protein kinase
      kinase 4 (MKK4) signaling attenuates neuronal damage during later ischemia
      reperfusion.
AB  - Mitogen-activated protein kinase kinase 4 (MKK4), as an upstream activator of c
      Jun NH(2)-terminal kinase (JNK), plays a critical role in response to cellular
      stresses and pro-inflammatory cytokines. In this study, we investigated the
      subcellular localization and activation of MKK4 in response to global cerebral
      ischemia. Our results indicated that MKK4 had two activation peaks in both the
      cytosol and the nucleus, and translocated from the cytosol to the nucleus at 30
      min and 6 h of reperfusion. We also detected the interaction of JNK-interacting
      protein 3 (JIP3) and MKK4, which reached a maximum at 6 h of reperfusion. To
      elucidate the mechanism of translocation and activation, we administered N
      acetylcysteine, an antioxidant reagent, and a glutamate receptor 6 C-terminus
      containing peptide (Tat-GluR6-9c) to rats. The data showed that N-acetylcysteine
      limited the translocation and activation at 30 min of reperfusion; however, the
      peptide perturbed the subcellular localization and activation at 6 h of
      reperfusion, and subsequently provided a protective role against delayed neuronal
      cell death. Taken together, these results demonstrate that the translocation and
      activation of MKK4 during early reperfusion are closely associated with reactive
      oxygen species, whereas, at late reperfusion, MKK4 activation may be involved in
      brain ischemic injury.

PMID- 16805807
TI  - Increased calcitonin gene-related peptide in neuroma and invading macrophages is
      involved in the up-regulation of interleukin-6 and thermal hyperalgesia in a rat
      model of mononeuropathy.
AB  - The pain related peptide, calcitonin gene-related peptide (CGRP), plays an
      important role in inflammatory pain and immune responses. However, its role in
      neuropathic pain is not established. Following nerve injury, CGRP and pro
      inflammatory interleukin-6 (IL-6) are increased in injured nerves. The aim of
      this study was to determine if CGRP in injured nerves is involved in the up
      regulation of IL-6 and in the maintenance of neuropathic pain. Perineural
      injection of a neutralizing IL-6 antiserum or CGRP receptor antagonists (CGRP8-37
      and BIBN4096BS) effectively attenuated thermal hyperalgesia 4 weeks after partial
      sciatic nerve ligation. Perineural CGRP antagonists also dramatically reduced IL
      6 level in injured nerves. CGRP release from injured sites was dramatically
      increased and CGRP immunoreactivity was localized in both neuroma and invading
      macrophages. CGRP receptor markers (CRLR and RAMP1) were expressed in invading
      macrophages. Both CGRP antagonists significantly reduced IL-6 release from
      injured nerve explants. In cell cultures derived from injured nerves, CGRP
      concentration-dependently increased IL-6 release, an effect also blocked by CGRP
      antagonists. Taken together, these data show that increased levels of CGRP in
      injured neuroma and invading macrophages are involved in the up-regulation of IL
      6 in macrophages as well as in the maintenance of neuropathic pain.

PMID- 16805808
TI  - In vitro and ex vivo evaluation of second-generation histone deacetylase
      inhibitors for the treatment of spinal muscular atrophy.
AB  - Among a panel of histone deacetylase (HDAC) inhibitors investigated,
      suberoylanilide hydroxamic acid (SAHA) evolved as a potent and non-toxic
      candidate drug for the treatment of spinal muscular atrophy (SMA), an alpha
      motoneurone disorder caused by insufficient survival motor neuron (SMN) protein
      levels. SAHA increased SMN levels at low micromolar concentrations in several
      neuroectodermal tissues, including rat hippocampal brain slices and motoneurone
      rich cell fractions, and its therapeutic capacity was confirmed using a novel
      human brain slice culture assay. SAHA activated survival motor neuron gene 2
      (SMN2), the target gene for SMA therapy, and inhibited HDACs at submicromolar
      doses, providing evidence that SAHA is more efficient than the HDAC inhibitor
      valproic acid, which is under clinical investigation for SMA treatment. In
      contrast to SAHA, the compounds m-Carboxycinnamic acid bis-Hydroxamide, suberoyl
      bishydroxamic acid and M344 displayed unfavourable toxicity profiles, whereas MS
      275 failed to increase SMN levels. Clinical trials have revealed that SAHA, which
      is under investigation for cancer treatment, has a good oral bioavailability and
      is well tolerated, allowing in vivo concentrations shown to increase SMN levels
      to be achieved. Because SAHA crosses the blood-brain barrier, oral administration
      may allow deceleration of progressive alpha-motoneurone degeneration by
      epigenetic SMN2 gene activation.

PMID- 16805809
TI  - Mitochondrial dysfunction and increased sensitivity to excitotoxicity in mice
      deficient in DNA mismatch repair.
AB  - The expression profile in the hippocampus of mice lacking one allele of the MutS
      homologue (Msh2), gene, which is one of the most representative components of the
      DNA mismatch repair system, was analysed to understand whether defects in the
      repair or in response to DNA damage could impact significantly on brain function.
      The overall results suggested a reduction in mitochondrial function as indicated
      by gene expression analysis, biochemical and behavioural studies. In the
      hippocampus of Msh2+/- mice, array data, validated by RT-PCR and western blot
      analysis, showed reduced expression levels of genes for cytochrome c oxidase
      subunit 2 (CoxII), ATP synthase subunit beta and superoxide dismutase 1.
      Biochemically, mitochondria from the hippocampus and cortex of these mice show
      reduced CoxII and increased aconitase activity. Behaviourally, these alterations
      resulted in mice with increased vulnerability to kainic acid-induced epileptic
      seizures and hippocampal neuronal loss. These data suggest that lack of an
      efficient system involved in recognizing and repairing DNA damage may generate a
      brain mitochondriopathy.

PMID- 16805811
TI  - Second messenger and Ras/MAPK signalling pathways regulate CLOCK/CYCLE-dependent
      transcription.
AB  - The heterodimeric complex of the transcription factors CLOCK (CLK) and CYCLE
      (CYC) constitutes the positive element of the circadian clock in Drosophila and
      mammals. Phosphorylation of clock proteins represents an essential mechanism for
      promotion and control of the molecular oscillator. However, the kinases and
      signalling pathways that regulate CLK/CYC function remain largely elusive. In the
      present study we performed a chemical screen of kinase inhibitors in a cell
      culture reporter assay to identify functional regulators of CLK/CYC-dependent
      gene expression. These studies and analysis of constitutively active forms of
      kinases revealed that cyclic nucleotide/protein kinase A (PKA),
      calcium/calmodulin-dependent kinase (CaMK) II and Ras/mitogen-activated protein
      kinase (MAPK) regulate CLK/CYC activity. In vitro phosphorylation analysis showed
      a direct phosphorylation of CLK by CaMK II and p42 MAPK [extracellular signal
      regulated kinase (ERK) 2], suggesting that these kinases regulate CLK/CYC
      dependent transcription by direct phosphorylation of CLK.

PMID- 16805810
TI  - Tissue inhibitor of metalloproteinase-2 (TIMP-2) expression is regulated by
      multiple neural differentiation signals.
AB  - Neuronal differentiation requires exquisitely timed cell cycle arrest for
      progenitors to acquire an appropriate neuronal cell fate and is achieved by
      communication between soluble signals, such as growth factors and extracellular
      matrix molecules. Here we report that the expression of TIMP-2, a matrix
      metalloproteinase inhibitor, is up-regulated by signals that control
      proliferation (bFGF and EGF) and differentiation (retinoic acid and NGF) in
      neural progenitor and neuroblastoma cell lines. TIMP-2 expression coincides with
      the appearance of neurofilament-positive neurons, indicating that TIMP-2 may play
      a role in neurogenesis. The up-regulation of TIMP-2 expression by proliferate
      signals suggests a role in the transition from proliferation to neuronal
      differentiation. Live labeling experiments demonstrate TIMP-2 expression only on
      alpha(3) integrin-positive cells. Thus, TIMP-2 function may be mediated via
      interaction with integrin receptor(s). We propose that TIMP-2 represents a
      component of the neurogenic signaling cascade induced by mitogenic stimuli that
      may withdraw progenitor cells from the cell cycle permitting their terminal
      neuronal differentiation.

PMID- 16805812
TI  - Interleukin-1-induced neurotoxicity is mediated by glia and requires caspase
      activation and free radical release.
AB  - Interleukin (IL)-1 expression is induced rapidly in response to diverse CNS
      insults and is a key mediator of experimentally induced neuronal injury. However,
      the mechanisms of IL-1-induced neurotoxicity are unknown. The aim of the present
      study was to examine the toxic effects of IL-1 on rat cortical cell cultures.
      Treatment with IL-1beta did not affect the viability of pure cortical neurones.
      However, IL-1 treatment of cocultures of neurones with glia or purified
      astrocytes induced caspase activation resulting in neuronal death. Neuronal cell
      death induced by IL-1 was prevented by pre-treatment with the IL-1 receptor
      antagonist, the broad spectrum caspase inhibitor Boc-Asp-(OMe)-CH(2)F or the
      antioxidant alpha-tocopherol. The NMDA receptor antagonist dizolcipine (MK-801)
      attenuated cell death induced by low doses of IL-1beta but the alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 2,3-dihydroxy-6
      nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) had no effect. Inhibition of
      inducible nitric oxide synthase with N(omega)-nitro-l-arginine methyl ester had
      no effect on neuronal cell death induced by IL-1beta. Thus, IL-1 activates the IL
      1 type 1 receptor in astrocytes to induce caspase-dependent neuronal death, which
      is dependent on the release of free radicals and may contribute to neuronal cell
      death in CNS diseases.

PMID- 16805813
TI  - Cannabinoids attenuate norepinephrine-induced melatonin biosynthesis in the rat
      pineal gland by reducing arylalkylamine N-acetyltransferase activity without
      involvement of cannabinoid receptors.
AB  - Cannabinoids modulate neuronal and neuroendocrine circuits by binding to
      cannabinoid receptors acting upon cAMP/Ca(2+)-mediated intracellular signaling
      cascades. The rat pineal represents an established model to investigate
      intracellular signaling processes because a well defined input, the
      neurotransmitter norepinephrine, is transformed via cAMP/Ca(2+)-dependent
      mechanisms into an easily detectable output signal, the biosynthesis of
      melatonin. Here we investigated the impact of cannabinoids on norepinephrine
      regulated melatonin biosynthesis in the rat pineal. We demonstrated that
      treatment of cultured rat pineals with 9-carboxy-11-nor-delta-9
      tetrahydrocannabinol (THC), cannabidiol or cannabinol significantly reduced
      norepinephrine-induced arylalkylamine N-acetyltransferase (AANAT) activity and
      melatonin biosynthesis. These effects were not mimicked by the cannabinoid
      receptor agonist WIN55,212-2 and were not blocked by cannabinoid 1 and 2 receptor
      antagonists. The cannabinoids used did not affect norepinephrine-induced
      increases in cAMP/Ca(2+) levels. Notably, cannabinoids were found to directly
      inhibit AANAT activity in lysates of the pineal gland. This effect was specific
      in so far as cannabinoids did not influence the activity of hydroxyindole-O
      methyltransferase (HIOMT), the last enzyme in melatonin biosynthesis. Taken
      together, our data strongly suggest that cannabinoids inhibit AANAT activity and
      attenuate melatonin biosynthesis through intracellular actions without
      involvement of classical cannabinoid receptor-dependent signaling cascades.

PMID- 16805814
TI  - Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for
      active uptake of L-lactate and ketone bodies in the brain.
AB  - SMCT1 is a sodium-coupled (Na(+)-coupled) transporter for l-lactate and short
      chain fatty acids. Here, we show that the ketone bodies, beta-d-hydroxybutyrate
      and acetoacetate, and the branched-chain ketoacid, alpha-ketoisocaproate, are
      also substrates for the transporter. The transport of these compounds via human
      SMCT1 is Na(+)-coupled and electrogenic. The Michaelis constant is 1.4 +/- 0.1 mm
      for beta-d-hydroxybutyrate, 0.21 +/- 0.04 mm for acetoacetate and 0.21 +/- 0.03
      mm for alpha-ketoisocaproate. The Na(+) : substrate stoichiometry is 2 : 1. As l
      lactate and ketone bodies constitute primary energy substrates for neurons, we
      investigated the expression pattern of this transporter in the brain. In situ
      hybridization studies demonstrate widespread expression of SMCT1 mRNA in mouse
      brain. Immunofluorescence analysis shows that SMCT1 protein is expressed
      exclusively in neurons. SMCT1 protein co-localizes with MCT2, a neuron-specific
      Na(+)-independent monocarboxylate transporter. In contrast, there was no overlap
      of signals for SMCT1 and MCT1, the latter being expressed only in non-neuronal
      cells. We also demonstrate the neuron-specific expression of SMCT1 in mixed
      cultures of rat cortical neurons and astrocytes. This represents the first report
      of an Na(+)-coupled transport system for a major group of energy substrates in
      neurons. These findings suggest that SMCT1 may play a critical role in the entry
      of l-lactate and ketone bodies into neurons by a process driven by an
      electrochemical Na(+) gradient and hence, contribute to the maintenance of the
      energy status and function of neurons.

PMID- 16805815
TI  - Phosphorylation of CaMKII at Thr253 occurs in vivo and enhances binding to
      isolated postsynaptic densities.
AB  - Autophosphorylation of Ca(2+)-calmodulin stimulated protein kinase II (CaMKII) at
      two sites (Thr286 and Thr305/306) is known to regulate the subcellular location
      and activity of this enzyme in vivo. CaMKII is also known to be
      autophosphorylated at Thr253 in vitro but the functional effect of
      phosphorylation at this site and whether it occurs in vivo, is not known. Using
      antibodies that specifically recognize CaMKII phosphorylated at Thr253 together
      with FLAG-tagged wild type and phospho- and dephospho-mimic mutants of alpha
      CaMKII, we have shown that Thr253 phosphorylation has no effect on either the
      Ca(2+)-calmodulin dependent or autonomous kinase activity of recombinant alpha
      CaMKII in vitro. However, the Thr253Asp phosphomimic mutation increased alpha
      CaMKII binding to subcellular fractions enriched in post-synaptic densities
      (PSDs). The increase in binding was similar in extent, and additive, to that
      produced by phosphorylation of Thr286. Thr253 phosphorylation was dynamically
      regulated in intact hippocampal slices. KCl induced depolarisation increased
      Thr253 phosphorylation and the phospho-Thr253-CaMKII was specifically recovered
      in the subcellular fraction enriched in PSDs. These results identify Thr253 as an
      additional site at which CaMKII is phosphorylated in vivo and suggest that this
      dynamic phosphorylation may regulate CaMKII function by altering its distribution
      within the cell.

PMID- 16805816
TI  - Conserved residues in juxtamembrane region of the extracellular domain of
      nicastrin are essential for gamma-secretase complex formation.
AB  - The Alzheimer's disease-linked protein, presenilin, forms the active site of the
      gamma-secretase enzyme complex. However, three other proteins, nicastrin (NCT),
      PEN-2 and APH-1, are required for enzyme activity. This complex is responsible
      for cleaving the beta-amyloid precursor protein to produce amyloid beta and the
      intracellular domain (AICD). Although much research has focused on the regions of
      presenilin that are important for gamma-secretase function, less is known about
      NCT. To further our understanding of the role of NCT in gamma-secretase activity
      and complex formation, we have undertaken a systematic evaluation of conserved
      residues in the juxtamembrane region of the extracellular domain of NCT. Two
      mutants, S632A and W648A, greatly reduce gamma-secretase activity, as seen by a
      reduction in amyloid beta and AICD levels. Several lines of evidence suggest that
      these mutations result in reduced gamma-secretase activity because they affect
      the ability of NCT to stably associate with the other gamma-secretase components.
      Since NCT and APH-1 must first bind in order for presenilin and PEN-2 to stably
      join the complex, we propose that S632 and W648 are essential for a stable
      interaction with APH-1.

PMID- 16805817
TI  - Generation of constitutively active calcineurin by calpain contributes to delayed
      neuronal death following mouse brain ischemia.
AB  - Calpain, a Ca(2+)-dependent cysteine protease, in vitro converts calcineurin
      (CaN) to constitutively active forms of 45 kDa and 48 kDa by cleaving the
      autoinhibitory domain of the 60 kDa subunit. In a mouse middle cerebral artery
      occlusion (MCAO) model, calpain converted the CaN A subunit to the constitutively
      active form with 48 kDa in vivo. We also confirmed increased Ca(2+)/CaM
      independent CaN activity in brain extracts. The generation of constitutively
      active and Ca(2+)/CaM-independent activity of CaN peaked 2 h after reperfusion in
      brain extracts. Increased constitutively active CaN activity was associated with
      dephosphorylation of dopamine-regulated phosphoprotein-32 in the brain.
      Generation of constitutively active CaN was accompanied by translocation of
      nuclear factor of activated T-cells (NFAT) into nuclei of hippocampal CA1
      pyramidal neurons. In addition, a novel calmodulin antagonist, DY-9760e, blocked
      the generation of constitutively active CaN by calpain, thereby inhibiting NFAT
      nuclear translocation. Together with previous studies indicating that NFAT plays
      a critical role in apoptosis, we propose that calpain-induced CaN activation in
      part mediates delayed neuronal death in brain ischemia.

PMID- 16805818
TI  - Predictive factors for response to docetaxel in human breast cancers.
AB  - Docetaxel has come into wide use recently for the treatment of breast cancer in
      neoadjuvant, adjuvant and metastatic settings. Docetaxel binds to beta-tubulin
      and causes kinetic abnormalities in the dynamics of microtubules by increasing
      their polymerization and inhibiting their depolymerization, resulting in elevated
      levels of microtubule formation. During metaphase, defective spindle formation
      induced by docetaxel activates the mitotic checkpoint and leads to cell cycle
      arrest, culminating in apoptosis. However, docetaxel is not effective for all
      breast cancers. For example, in metastatic settings, the response rate to
      docetaxel reportedly ranges from 30 to 50%. It is therefore very important to
      develop a diagnostic method with high accuracy for the prediction of sensitivity
      to docetaxel in order to avoid unnecessary treatment. Currently it is impossible
      to identify, before the initiation of therapy, the patients for whom docetaxel
      will be effective. Various biological parameters have been studied clinically for
      their ability to predict response to docetaxel, such as parameters related to:
      (1) efflux (p-glycoprotein) and metabolism (CYP3A4); (2) beta-tubulin (somatic
      mutation of beta-tubulin and changes in beta-tubulin isotypes levels); (3) cell
      cycle (HER2, BRCA1 and Aurora-A); and (4) apoptosis (p53, BCL2 and thioredoxin).
      More recently, gene expression profiling techniques have been used for the
      development of a prediction model for response to docetaxel. In the present
      paper, clinical studies that have been conducted recently to identify predictive
      factors for response to docetaxel are reviewed together with a presentation of
      our recent work in this field.

PMID- 16805819
TI  - Plausible linkage of hypoxia inducible factor-1alpha in uterine cervical cancer.
AB  - Angiogenesis is essential for the development, growth and advancement of solid
      tumors. Angiogenesis is induced by hypoxia with angiogenic transcription factor
      hypoxia inducible factors (HIF). This prompted us to study the clinical
      implications of HIF relative to angiogenesis in uterine cervical cancers.
      Although there was no significant difference in HIF-1alpha histoscores and mRNA
      levels according to histopathological type or lymph node metastasis, HIF-1alpha
      histoscores and mRNA levels increased significantly with advancing cancer stages.
      The prognosis of 30 patients with high HIF-1alpha in uterine cervical cancers was
      poor (73% survival), whereas the 24-month survival rate of the other 30 patients
      with low HIF-1alpha was 93%. HIF-1alpha histoscores and mRNA levels were
      correlated with the levels of the angiogenic factors thymidine phosphorylase and
      interleukin-8, and HIF-1alpha might be linked with these factors in cervical
      cancer tissue. HIF-1alpha is a candidate for prognostic indicator as an
      angiogenic mediator in uterine cervical cancer.

PMID- 16805820
TI  - Centrosome amplification in adult T-cell leukemia and human T-cell leukemia virus
      type 1 Tax-induced human T cells.
AB  - Centrosomes play pivotal roles in cell polarity, regulation of the cell cycle and
      chromosomal segregation. Centrosome amplification was recently described as a
      possible cause of aneuploidy in certain solid tumors and leukemias. ATL is a T
      cell malignancy caused by HTLV-1. Although the precise mechanism of cell
      transformation is unclear, the HTLV-1-encoded protein, Tax, is thought to play a
      crucial role in leukemogenesis. Here we demonstrate that lymphocytes isolated
      from patients with ATL show centrosome amplification and that a human T cell line
      shows centrosome amplification after induction of Tax, which was suppressed by
      CDK inhibitors. Micronuclei formation was also observed after centrosome
      amplification in Tax-induced human T cells. These findings suggest that Tax
      deregulates CDK activity and induces centrosome amplification, which might be
      associated with cellular transformation by HTLV-1 and chromosomal instability in
      HTLV-1-infected human T cells.

PMID- 16805821
TI  - Synergic antiproliferative effect of DNA methyltransferase inhibitor in
      combination with anticancer drugs in gastric carcinoma.
AB  - Epigenetic alterations of DNA methylation play an important role in the
      regulation of gene expression associated with chemosensitivity of gastric
      carcinomas. With the aim of improving the chemotherapeutic efficacy of gastric
      carcinoma, the effect of DNA methyltransferase inhibitor, 5-aza-CdR, on the
      chemosensitivity of five anticancer drugs was investigated. Human gastric cancer
      cell lines, OCUM-2M and MKN-74, and five anticancer drugs, 5-FU, PTX, OXA, SN38,
      and GEM, were used. In both gastric cancer cell lines, a synergistic
      antiproliferative effect by a combination of 5-aza-CdR at 5 microM was found in
      SN38 and GEM. 5-Aza-CdR at 5 microM increased apoptosis induced by SN38 and GEM
      in both cell lines. 5-Aza-CdR increases the expression of DAPK-2 and DAPK-3,
      RASSF1, and THBS1 genes in both OCUM-2M and MKN-74 cells, but not that of hMLH1,
      p16, MGMT, E-cadherin, and p53 genes. These findings suggest that 5-aza-CdR is a
      promising chemotherapeutical agent for gastric carcinomas, in combination with
      the anticancer drugs SN38 and GEM, in apoptosis signaling. The upregulation of
      DAPK-2 and DAPK-3, RASSF1, and THBS1 genes by 5-aza-CdR might be associated with
      the synergistic effect.

PMID- 16805822
TI  - Complementary activation of peripheral natural killer cell immunity in
      nasopharyngeal carcinoma.
AB  - NK cells and alphabeta- and gammadelta-CTL play important roles in cellular
      immunity against tumors. We previously demonstrated that NPC patients have a
      quantitative and qualitative deficit in gammadelta-CTL and EBV-specific alphabeta
      CTL when compared to normal subjects and NPC long-term survivors. In this study
      we report further observations of a complementary activation of peripheral NK
      cells in NPC patients. The NK cells in these patients, compared to those of
      healthy subjects and NPC survivors, were preferentially activated in response to
      the stimulation of myeloma cell line XG-7 and expanded in the presence of
      exogenous IL-2. The production of IFN-gamma was lowest in the patient group,
      whereas IL-12, IL-15 and TNF-alpha were produced in higher levels in patients
      than in the donors and survivors. The cytolytic effect of the NK cells against
      NPC cells in the patient group was also higher than that of the donors and
      survivors. Furthermore, the patients at later stages of NPC had lower gammadelta
      CTL activity but higher NK cytotoxicity towards NPC targets, with higher
      production of IL-12, IL-15 and TNF-alpha but lower production of IFN-gamma than
      in patients at earlier stages. This might be part of a triggered compensatory re
      activation of the innate immunity, believed to be mediated through various
      cytokines and chemokines when adaptive T cell immunity is breached. Together,
      these data suggest complementary roles of innate and adaptive immune response in
      tumor immunity where NK cells, gammadelta- and alphabeta-CTL compensate for the
      deficits of one another at different stages of tumor invasion.

PMID- 16805823
TI  - Involvement of a novel ADP-ribosylation factor GTPase-activating protein, SMAP,
      in membrane trafficking: implications in cancer cell biology.
AB  - The endocytosis of cell membrane proteins is initiated by the binding of
      activated Arf6, a member of Ras-related GTPases, to the PM. A GAP specific for
      Arf6 triggers the budding of endocytotic vesicles from the PM by inactivating GTP
      bound Arf6. We recently identified the SMAP gene that encodes an ArfGAP and is
      involved in the endocytosis of TfnR and possibly E-cadherin. In this review, we
      summarize the process of intracellular membrane trafficking, highlighting the
      roles played by the SMAP gene. Progression of cancer to malignancy occurs in
      parallel with the disappearance of E-cadherin, a central component of the
      adherens junction in epithelial cells. Therefore, elucidation of the molecular
      mechanism of E-cadherin endocytosis should be one of the key elements in tumor
      cell biology.

PMID- 16805824
TI  - Inhibition of peroxisome proliferator-activated receptor gamma activity in
      esophageal carcinoma cells results in a drastic decrease of invasive properties.
AB  - Esophageal cancer is difficult to treat because of its rapid progression, and
      more effective therapeutic approaches are needed. The PPARgamma is a nuclear
      receptor superfamily member that is expressed in many cancers. PPARgamma
      expression is a feature of esophageal cancer cell lines, and in the present
      investigation, the PPARgamma antagonists T0070907 and GW9662 could induce loss of
      invasion but could not induce growth reduction or apoptosis at low concentrations
      (< 10 mM). A high concentration of antagonists (50 microM) inhibited cell growth
      and induced apoptosis, but these effects did not explain our result at the low
      concentration. Morphological change, decreased expression of the cell signaling
      pathway and inhibition of cancer cell invasion were observed in the low
      concentration. This suggested that PPARgamma antagonists inhibited esophageal
      cancer cell invasion as well as cell adherence, most likely due to alteration in
      the FAK-MAPK pathway, and this was independent of apoptosis. These results
      suggested that PPARgamma plays an important role in cancer cell invasion and that
      it might be a novel target for therapy of esophageal cancer.

PMID- 16805825
TI  - Phase II study of the CPT-11, mitoxantrone and dexamethasone regimen in
      combination with rituximab in elderly patients with relapsed diffuse large B-cell
      lymphoma.
AB  - Standard treatment for elderly patients with relapsed or refractory DLBCL has not
      been established. CPT-11 has a broad spectrum of anticancer activities including
      a cytotoxic effect in a variety of malignant tumors. The results of combined
      treatment with CPT-11 and rituximab have not been reported. The R-CMD regimen was
      given to elderly patients with relapsed or refractory DLBCL. The safety and
      efficacy of this regimen were studied. In addition, the serum nm23-H1 level was
      determined to study whether or not it can serve as a prognostic factor. Thirty
      elderly patients with DLBCL were studied. The main non-hematological toxicities
      were infusion-related adverse events. Grade 3/4 hematological toxicity was seen
      in 19 patients. Following R-CMD treatment, the BNP and troponin T levels did not
      increase. The CR rate was 57%, PR rate was 17%, 2-year survival rate was 45.2%,
      and PFS rate was 37.2%. Patients with serum nm23-H1 levels of higher than 80
      ng/mL before the treatment showed significantly poorer prognosis. The serum nm23
      H1 level of the 30 subjects before the treatment was elevated at 39.4 +/- 41.3
      ng/mL, but it significantly decreased only in the subset of patients who achieved
      CR. The R-CMD regimen was safe in elderly patients with DLBCL. No new signs of
      cardiotoxicity were observed with this regimen. It was also effective in patients
      with relapsed or refractory DLBCL who had previously used DXR.

PMID- 16805826
TI  - In vivo mutagenicity and initiation following oxidative DNA lesion in the kidneys
      of rats given potassium bromate.
AB  - To clarify the role of 8-OHdG formation as a starting point for carcinogenesis,
      we examined the dose-dependence and time-course of changes of OGG1 mRNA
      expression, 8-OHdG levels and in vivo mutations in the kidneys of gpt delta rats
      given KBrO3 in their drinking water for 13 weeks. There were no remarkable
      changes in OGG1 mRNA in spite of some increments being statistically significant.
      Increases of 8-OHdG occurred after 1 week at 500 p.p.m. and after 13 weeks at 250
      p.p.m. Elevation of Spi- mutant frequency, suggestive of deletion mutations,
      occurred after 9 weeks at 500 p.p.m. In a two-stage experiment, F344 rats were
      given KBrO3 for 13 weeks then, after a 2-week recovery, treated with 1% NTA in
      the diet for 39 weeks. The incidence and multiplicity of renal preneoplastic
      lesions in rats given KBrO3 at 500 p.p.m. followed by NTA treatment were
      significantly higher than in rats treated with NTA alone. Results suggest that a
      certain period of time might be required for 8-OHdG to cause permanent mutations.
      The two-step experiment shows that cells exposed to the alteration of the
      intranuclear status by oxidative stress including 8-OHdG formation might be able
      to form tumors with appropriate promotion.

PMID- 16805827
TI  - The neurotrophic effects of PACAP in PC12 cells: control by multiple transduction
      pathways.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal polypeptide (VIP) are closely related members of the secretin
      superfamily of neuropeptides expressed in both the brain and peripheral nervous
      system, and they exhibit neurotrophic and neurodevelopmental effects in vivo.
      Like the index member of the Trk receptor ligand family, nerve growth factor
      (NGF), PACAP promotes the differentiation of PC12 cells, a well-established cell
      culture model, to investigate neuronal differentiation, survival and function.
      Stimulation of catecholamine secretion and enhanced neuropeptide biosynthesis are
      effects exerted by PACAP at the adrenomedullary synapse in vivo and on PC12 cells
      in vitro through stimulation of the specific PAC1 receptor. Induction of
      neuritogenesis, growth arrest, and promotion of cell survival are effects of
      PACAP that occur in developing cerebellar, hippocampal and cortical neurons, as
      well as in the more tractable PC12 cell model. Study of the mechanisms through
      which PACAP exerts its various effects on cell growth, morphology, gene
      expression and survival, i.e. its actions as a neurotrophin, in PC12 cells is the
      subject of this review. The study of neurotrophic signalling by PACAP in PC12
      cells reveals that multiple independent pathways are coordinated in the PACAP
      response, some activated by classical and some by novel or combinatorial
      signalling mechanisms.

PMID- 16805828
TI  - The region-specific activities of lipid rafts during axon growth and guidance.
AB  - The generation and control of cell polarity is a fundamental mechanism for
      directed migration of the cell. In developing neurons, the axonal growth cone
      recognizes environmental molecular cues and migrates toward its correct target,
      thereby forming neuronal networks. The spatial information provided by
      environmental cues directs axon growth and guidance through generating polarity
      of intracellular signals and cytoskeletal organization in the growth cone. This
      polarization process is dependent on lipid rafts, specialized microdomains in the
      cell membrane. Lipid rafts in specific regions of the growth cone are involved in
      axon growth and guidance. For example, forward migration of the growth cone
      requires raft membranes in its leading front. Recent experiments have suggested
      that lipid rafts function as a platform for localized signaling downstream of
      adhesion molecules and guidance receptors. The rafts assemble into an active
      membrane domain that captures and reorganizes the cytoskeletal machinery. In this
      way, the spatial control of signaling through raft membranes plays a critical
      role in translating extracellular information into polarized motility of the
      growth cone.

PMID- 16805829
TI  - Phosphoinositide regulation of neuroexocytosis: adding to the complexity.
AB  - Exocytosis of neurotransmitter containing vesicles supports neuronal
      communication. The importance of molecular interactions involving specific lipids
      has become progressively more evident and the lipid composition of both the
      synaptic vesicle and the pre-synaptic plasma membrane at the active zone has
      significant functional consequences for neurotransmitter release. Several classes
      of lipids have been implicated in exocytosis including polyunsaturated fatty
      acids and phosphoinositides. This minireview will focus on recent developments
      regarding the role of phosphoinositides in neurosecretion.

PMID- 16805830
TI  - Interaction of the brain-specific protein p42IP4/centaurin-alpha1 with the
      peptidase nardilysin is regulated by the cognate ligands of p42IP4,
      PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4, with stereospecificity.
AB  - The brain-specific protein p42IP4, also called centaurin-alpha1, specifically
      binds phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and inositol
      1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. Here, we investigate the interaction
      of p42IP4/centaurin-alpha1 with nardilysin (NRDc), a member of the M16 family of
      zinc metalloendopeptidases. Members of this peptidase family exhibit enzymatic
      activity and also act as receptors for other proteins. We found that
      p42IP4/centaurin-alpha1 binds specifically to NRDc from rat brain. We further
      detected that centaurin-alpha2, a protein that is highly homologous to
      p42IP4/centaurin-alpha1 and expressed ubiquitously, also binds to NRDc. In vivo
      interaction was demonstrated by co-immunoprecipitation of p42IP4/centaurin-alpha1
      with NRDc from rat brain. The acidic domain of NRDc (NRDc-AD), which does not
      participate in catalysis, is sufficient for the protein interaction with p42IP4.
      Interestingly, preincubation of p42IP4 with its cognate ligands D-Ins(1,3,4,5)P4
      and the lipid diC8PtdIns(3,4,5)P3 negatively modulates the interaction between
      the two proteins. D-Ins(1,3,4,5)P4 and diC8PtdIns(3,4,5)P3 suppress the
      interaction with virtually identical concentration dependencies. This inhibition
      is highly ligand specific. The enantiomer L-Ins(1,3,4,5)P4 is not effective.
      Similarly, the phosphoinositides diC8PtdIns(3,4)P2, diC8PtdIns(3,5)P2 and
      diC8PtdIns(4,5)P2 all have no influence on the interaction. Further experiments
      revealed that endogenous p42IP4 from rat brain binds to glutathione-S-transferase
      (GST)-NRDc-AD. The proteins dissociate from each other when incubated with D
      Ins(1,3,4,5)P4, but not with inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. In
      summary, we demonstrate that p42IP4 binds to NRDc via the NRDc-AD, and that this
      interaction is controlled by the cognate cellular ligands of p42IP4/centaurin
      alpha1. Thus, specific ligands of p42IP4 can modulate the recruitment of
      proteins, which are docked to p42IP4, to specific cellular compartments.

PMID- 16805831
TI  - Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12
      cells.
AB  - We examined the effect of the three human isoforms of apolipoprotein E (ApoE2,
      ApoE3, and ApoE4) on the canonical Wnt signaling pathway in undifferentiated PC12
      cells. Addition of recombinant ApoE4 reduced Wingless-Int7a-stimulated gene
      expression at concentrations of 80 and 500 nm. Recombinant ApoE2 and ApoE3 were
      virtually inactive. Recombinant ApoE4 also inhibited Wnt signaling when combined
      with very low density lipoproteins (VLDLs) or in cells over-expressing the low
      density lipoprotein receptor-related protein, LRP6. In contrast, the enforced
      expression of LRP5 unmasked an inhibition by ApoE2 and ApoE3, which, however,
      were less effective than ApoE4 in inhibiting Wnt signaling. We also transfected
      PC12 cells with constructs encoding for the three human ApoE isoforms to examine
      whether endogenously expressed ApoE isoforms could modulate the Wnt pathway.
      Under these conditions, all three ApoE isoforms were able to inhibit Wnt
      signaling, although ApoE4 showed the greatest efficacy. Only the conditioned
      medium collected from cultures transfected with ApoE4 induced a significant
      inhibition of Wnt7a-stimulated gene expression, confirming that ApoE4 has an
      extracellular action that is not shared by the other ApoE isoforms. We conclude
      that ApoE4 behaves as an inhibitor of the canonical Wnt pathway in a context
      independent manner.

PMID- 16805832
TI  - Thioredoxin inhibits NMDA-induced neurotoxicity in the rat retina.
AB  - Thioredoxin (TRX) plays a variety of redox-related roles in organisms. To
      investigate its function as an endogenous redox regulator in NMDA-induced retinal
      neurotoxicity, we injected NMDA with TRX, mutant TRX or saline into the vitreous
      cavity of rat eyes. Retinal ganglion cells were rescued by TRX, compared with
      saline, when evaluated by retrograde labeling analysis at 7 days after NMDA
      injection. TRX, but not its mutant form, prevented NMDA-induced apoptosis in the
      retina, as measured by terminal deoxynucleotidyl transferase-mediated UTP nick
      end labeling. The induction of caspase 3 and 9, but not caspase 8, by NMDA was
      significantly lower in TRX-treated eyes than in saline-treated eyes. NMDA-induced
      activation of the MAPKs, p38 kinase and c-Jun N-terminal kinase after 6 h and of
      the MAPK kinases (MKKs) MKK3/6 and MKK4 after 3 h was markedly suppressed in
      retinal ganglion cells by TRX but not by the mutant form. NMDA-induced increases
      in protein carbonylation, nitrosylation and lipid peroxidation were also
      suppressed in TRX-treated eyes. We concluded that the intravitreous injection of
      TRX effectively attenuated NMDA-induced retinal cell damage and that suppression
      of oxidative stress and inhibition of apoptotic signaling pathways were involved
      in this neuroprotection.

PMID- 16805833
TI  - Regulation of tyrosine hydroxylase gene expression by retinoic acid receptor.
AB  - Retinoic acid (RA), a derivative of vitamin A, critically controls brain
      patterning and neurogenesis during embryogenesis, and is known to regulate
      morphological differentiation of catecholaminergic neuronal cells. In this study,
      we investigated whether the retinoic acid receptor (RAR), a transcription factor
      specifically activated by all-trans-RA, could directly regulate transcription of
      tyrosine hydroxylase (TH), the first and rate-limiting step in the catecholamine
      biosynthesis pathway. First, treating TH-expressing human neuroblastoma SK-N
      BE(2)C cells with all-trans RA resulted in an approximately 1.7-fold increase in
      endogenous TH mRNA expression, as determined by real-time PCR analysis. Second,
      when SK-N-BE(2)C cells were transiently co-transfected with the TH promoter
      luciferase reporter construct, reporter gene expression was prominently activated
      by RAR in a ligand-dependent manner. Third, we identified a putative RAR
      responsive cis-regulatory element at - 1500 to - 1487 bp in the TH upstream
      promoter region by deletional and site-directed mutational analysis. Finally, we
      demonstrated that this putative motif directly interacts with RAR protein in a
      sequence-specific manner by means of an electrophoretic mobility shift assay.
      Taken together, our results indicate that the TH gene may be a direct downstream
      target of the RA signaling pathway and that RAR is able to activate TH
      transcription through interaction with an upstream sequence motif residing at -
      1500 to - 1487 bp.

PMID- 16805834
TI  - Molecular determinants of ginkgolide binding in the glycine receptor pore.
AB  - Ginkgolides are potent blockers of the glycine receptor Cl- channel (GlyR) pore.
      We sought to identify their binding sites by comparing the effects of ginkgolides
      A, B and C and bilobalide on alpha1, alpha2, alpha1beta and alpha2beta GlyRs.
      Bilobalide sensitivity was drastically reduced by incorporation of the beta
      subunit. In contrast, the sensitivities to ginkgolides B and C were enhanced by
      beta subunit expression. However, ginkgolide A sensitivity was increased in the
      alpha2beta GlyR relative to the alpha2 GlyR but not in the alpha1beta GlyR
      relative to the alpha1 GlyR. We hypothesised that the subunit-specific
      differences were mediated by residue differences at the second transmembrane
      domain 2' and 6' pore-lining positions. The increased ginkgolide A sensitivity of
      the alpha2beta GlyR was transferred to the alpha1beta GlyR by the G2'A (alpha1 to
      alpha2 subunit) substitution. In addition, the alpha1 subunit T6'F mutation
      abolished inhibition by all ginkgolides. As the ginkgolides share closely related
      structures, their molecular interactions with pore-lining residues were amenable
      to mutant cycle analysis. This identified an interaction between the variable R2
      position of the ginkgolides and the 2' residues of both alpha1 and beta subunits.
      These findings provide strong evidence for ginkgolides binding at the 2' pore
      lining position.

PMID- 16805835
TI  - Anandamide administration alone and after inhibition of fatty acid amide
      hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in
      rats.
AB  - Although endogenous cannabinoid systems have been implicated in the modulation of
      the rewarding effects of abused drugs and food, little is known about the direct
      effects of endogenous ligands for cannabinoid receptors on brain reward
      processes. Here we show for the first time that the intravenous administration of
      anandamide, an endogenous ligand for cannabinoid receptors, and its longer
      lasting synthetic analog methanandamide, increase the extracellular dopamine
      levels in the nucleus accumbens shell of awake, freely moving rats, an effect
      characteristic of most drugs abused by humans. Anandamide produced two distinctly
      different effects on dopamine levels: (1) a rapid, transient increase that was
      blocked by the cannabinoid CB1 receptor antagonist rimonabant, but not by the
      vanilloid VR1 receptor antagonist capsazepine, and was magnified and prolonged by
      the fatty acid amide hydrolase (FAAH) enzyme inhibitor, URB597; (2) a smaller
      delayed and long-lasting increase, not sensitive to CB1, VR1 or FAAH blockade.
      Both effects were blocked by infusing either tetrodotoxin (TTX, 1 microm) or
      calcium-free Ringer's solution through the microdialysis probe, demonstrating
      that they were dependent on the physiologic activation of dopaminergic
      neurotransmission. Thus, these results indicate that anandamide, through the
      activation of the mesolimbic dopaminergic system, participates in the signaling
      of brain reward processes.

PMID- 16805836
TI  - Regulation of ApC/EBP mRNA by the Aplysia AU-rich element-binding protein,
      ApELAV, and its effects on 5-hydroxytryptamine-induced long-term facilitation.
AB  - Aplysia CCAAT enhancer-binding protein (ApC/EBP), a key molecular switch in 5
      hydroxytryptamine (5-HT)-induced long-term facilitation of Aplysia, is quickly
      and transiently expressed in response to a 5-HT stimulus, but the mechanism
      underlying this dynamic expression profile remains obscure. Here, we report that
      the dynamic expression of ApC/EBP during long-term facilitation is regulated at
      the post-transcriptional level by AU-rich element (ARE)-binding proteins. We
      found that the 3'UTR of ApC/EBP mRNA contains putative sequences for ARE, which
      is a representative post-transcriptional cis-acting regulatory element that
      modulates the stability and/or the translatability of a distinct subset of labile
      mRNAs. We cloned the Aplysia homologue of embryonic lethal abnormal visual system
      homologue (ELAV/Hu) protein, one of the best-studied RNA-binding proteins that
      associate with ARE, and elucidated the involvement of Aplysia ELAV/Hu protein in
      ApC/EBP gene expressional regulation. Cloned Aplysia ELAV/Hu protein, Aplysia
      embryonic lethal abnormal visual system (ApELAV), bound to an AU-rich region
      within the 3'UTR of ApC/EBP mRNA. Additionally, ApELAV controlled the expression
      of ApC/EBP 3'UTR-containing reporter gene by functioning as a stability-enhancing
      factor. In particular, 5-HT-induced long-term facilitation was impaired when the
      AU-rich region within the 3'UTR of ApC/EBP was over-expressed, which suggests the
      significance of this region in 5-HT-induced ApC/EBP expression, and in the
      resultant formation of long-term facilitation. Our results imply that the Aplysia
      ARE-binding protein, ApELAV, can regulate ApC/EBP gene expression at the mRNA
      level, and accordingly, ARE-mediated post-transcriptional mechanism may serve a
      crucial function in regulating the expression of ApC/EBP in response to a 5-HT
      stimulus.

PMID- 16805837
TI  - Guanosine promotes the up-regulation of inward rectifier potassium current
      mediated by Kir4.1 in cultured rat cortical astrocytes.
AB  - Guanosine (Guo) is an endogenous neuroprotective molecule of the CNS, which has
      various acute and long-term effects on both neurones and astroglial cells.
      Whether Guo also modulates the activity/expression of ion channels involved in
      homeostatic control of extracellular potassium by the astrocytic syncytium is
      still unknown. Here we provide electrophysiological evidence that chronic
      exposure (48 h) to Guo (500 microm) promotes the functional expression of an
      inward rectifier K+ (Kir) conductance in primary cultured rat cortical
      astrocytes. Molecular screening indicated that Guo promotes the up-regulation of
      the Kir4.1 channel, the major component of the Kir current in astroglia in vivo.
      Furthermore, the properties of astrocytic Kir current overlapped those of the
      recombinant Kir4.1 channel expressed in a heterologous system, strongly
      suggesting that the Guo-induced Kir conductance is mainly gated by Kir4.1. In
      contrast, the expression levels of two other Kir channel proteins were either
      unchanged (Kir2.1) or decreased (Kir5.1). Finally, we showed that inhibition of
      translational process, but not depression of transcription, prevents the Guo
      induced up-regulation of Kir4.1, indicating that this nucleoside acts through de
      novo protein synthesis. Because accumulating data indicate that down-regulation
      of astroglial Kir current contributes to the pathogenesis of neurodegenerative
      diseases associated with dysregulation of extracellular K+ homeostasis, these
      results support the notion that Guo might be a molecule of therapeutic interest
      for counteracting the detrimental effect of K+-buffering impairment of the
      astroglial syncytium that occurs in pathological conditions.

PMID- 16805838
TI  - High glucose-induced activation of the polyol pathway and changes of gene
      expression profiles in immortalized adult mouse Schwann cells IMS32.
AB  - We investigated the polyol pathway activity and the gene expression profiles in
      immortalized adult mouse Schwann cells (IMS32) under normal (5.6 mM) and high (30
      and 56 mM) glucose conditions for 7-14 days in culture. Messenger RNA and the
      protein expression of aldose reductase (AR) and the intracellular sorbitol and
      fructose contents were up-regulated in IMS32 under high glucose conditions
      compared with normal glucose conditions. By employing DNA microarray and
      subsequent RT-PCR/northern blot analyses, we observed significant up-regulation
      of the mRNA expressions for serum amyloid A3 (SAA3), angiopoietin-like 4
      (ANGPTL4) and ecotropic viral integration site 3 (Evi3), and the down-regulation
      of aldehyde reductase (AKR1A4) mRNA expression in the cells under high glucose
      (30 mM) conditions. The application of an AR inhibitor, SNK-860, to the high
      glucose medium ameliorated the increased sorbitol and fructose contents and the
      reduced AKR1A4 mRNA expression, while it had no effect on mRNA expressions for
      SAA3, ANGPTL4 or Evi3. Considering that the exposure to the high glucose (>or= 30
      mM) conditions mimicking hyperglycaemia in vivo accelerated the polyol pathway in
      IMS32, but not in other previously reported Schwann cells, the culture system of
      IMS32 under those conditions may provide novel findings about the polyol pathway
      related abnormalities in diabetic neuropathy.

PMID- 16805839
TI  - Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of
      neural stem cells.
AB  - To investigate the effects of suppressors of cytokine signaling 3 (SOCS3) on
      neural stem cell fate, stem cells were infected with an adenoviral vector
      expressing SOCS3. Three days later, western blot analysis and immunocytochemical
      analysis revealed that the protein level of MAP2 and the number of MAP2-positive
      cells were significantly increased in SOCS3-transfected cells, whereas the
      protein level of GFAP and the number of GFAP-positive cells were significantly
      decreased. Furthermore, promoter assay revealed a significant reduction in the
      transcriptional level of signal transducer and activator of transcription 3
      (Stat3) in the transfected cells. In addition, the mRNA levels of Notch family
      member (notch1) and inhibitory basic helix-loop-helix (bHLH) factors (hes5 and
      id3) were significantly up-regulated 1 day after overexpression of SOCS3. Three
      days after transfection, the mRNA level of hes5 was significantly decreased,
      whereas that of notch1 was still up-regulated. Moreover, all of SOCS3-positive
      cells expressed Nestin protein but did not express MAP2 or GFAP proteins. These
      data indicate that overexpression of SOCS3 induced neurogenesis and inhibited
      astrogliogenesis in neural stem cells. Our data also show that SOCS3 promoted
      maintenance of neural stem cells.

PMID- 16805840
TI  - Structural stabilization of CNS synapses during postnatal development in rat
      cortex.
AB  - CNS synapses are produced rapidly upon pre- and post-synaptic recruitment.
      However, their composition is known to change during development and we reasoned
      that this may be reflected in the gross biochemical properties of synapses. We
      found synaptic structure in adult cortical synaptosomes to be resistant to
      digestion with trypsin in the presence and absence of calcium ions, contrasting
      with previous observations. We evaluated the divalent cation dependence and
      trypsin sensitivities of synapses using synaptosomes from different developmental
      stages. In contrast to adult synapses, at postnatal day (P) 10 EDTA treatment
      eliminated approximately 60% of the synapses, and trypsin and EDTA, together,
      eliminated all junctions. Trypsinization in the presence of calcium eliminated
      approximately 60% of the junctions at P10. By P35, all synapses were calcium
      independent, whereas full trypsin resistance was not attained until P49. To
      compare the calcium dependence and trypsin sensitivity of synapses in another
      region of the adult brain, we examined synapses from adult (P50) hippocampus.
      Adult hippocampus maintained a population of synapses that resembled that of P35
      cortex. Our results show that synapses are modified over a long time period in
      the developing cortex. We propose a model in which the addition of synergistic
      calcium-dependent and -independent adhesive systems stabilize synapses.

PMID- 16805841
TI  - Dopamine receptor regulation of Ca2+ levels in individual isolated nerve
      terminals from rat striatum: comparison of presynaptic D1-like and D2-like
      receptors.
AB  - We have directly observed the effects of activating presynaptic D1-like and D2
      like dopamine receptors on Ca2+ levels in isolated nerve terminals (synaptosomes)
      from rat striatum. R-(+)-SKF81297, a selective D1-like receptor agonist, and (-)
      quinpirole, a selective D2-like receptor agonist, induced increases in Ca2+
      levels in different subsets of individual striatal synaptosomes. The SKF81297-
      and quinpirole-induced effects were blocked by R-(+)-SCH23390, a D1-like receptor
      antagonist, and (-)-sulpiride, a D2-like receptor antagonist, respectively.
      SKF81297- or quinpirole-induced Ca2+ increases were inhibited following blockade
      of voltage-gated calcium channels or sodium channels. In a larger subset of
      synaptosomes, quinpirole decreased baseline Ca2+. Quinpirole also inhibited
      veratridine-induced increases in intrasynaptosomal Ca2+ level. Immunostaining
      confirmed the presynaptic expression of D1, D5, D2 and D3 receptors, but not D4
      receptors. The array of neurotransmitter phenotypes of the striatal nerve endings
      expressing D1, D5, D2 or D3 varied for each receptor subtype. These results
      suggest that presynaptic D1-like and D2-like receptors induce increases in Ca2+
      levels in different subsets of nerve terminals via Na+ channel-mediated membrane
      depolarization, which, in turn, induces the opening of voltage-gated calcium
      channels. D2-like receptors also reduce nerve terminal Ca2+ in a different but
      larger subset of synaptosomes, consistent with the predominant presynaptic action
      of dopamine in the striatum being inhibitory.

PMID- 16805842
TI  - Mature pig oligodendrocytes rapidly process human recombinant pro-nerve growth
      factor and do not undergo cell death.
AB  - The neurotrophin family with its first member, nerve growth factor (NGF), binds
      two classes of receptors, more specifically to Trk receptors and to a shared
      p75NTR receptor. It has been shown that proNGF rather than NGF is predominant in
      the mature central nervous system. A recent finding indicated that a furin
      resistant proNGF preferentially binds to p75NTR, initiating a pro-apoptotic
      cascade even in the presence of TrkA. In this context, rodent oligodendrocytes
      were reported to undergo cell death when exposed to proNGF. We have investigated
      the effect of a non-mutated 32 kDa human recombinant proNGF (rhproNGF) on
      cultured pig oligodendrocytes which express TrkA, p75NTR and sortilin. Pig
      oligodendrocytes respond to rhproNGF (50 ng/mL) with an enhanced regeneration of
      their processes as already observed for NGF. Activity of mitogen-activated
      protein kinase (MAPK), which plays an important role in oligodendroglial process
      formation, was increased even when rhproNGF processing was inhibited by the furin
      inhibitor Decanoyl-RVKR-CMK. Similarly, a cleavage-resistant proNGF (R-1G)
      activated MAPK and promoted oligodendroglial process regeneration. High
      concentrations of rhproNGF (300 ng/mL) did not induce cell death. Sodium dodecyl
      sulfate - polyacrylamide gel electrophoresis and Western blotting revealed that
      oligodendrocytes process rhproNGF to NGF. NGF was detected in Western blots of
      oligodendroglial lysates already 10 min after rhproNGF exposure, followed by a
      release of NGF into the culture medium. Indirect evidence indicates that rhproNGF
      processing occurs via an endocytotic route.

PMID- 16805843
TI  - Sodium channel beta4 subunit: down-regulation and possible involvement in
      neuritic degeneration in Huntington's disease transgenic mice.
AB  - Sodium channel beta4 is a very recently identified auxiliary subunit of the
      voltage-gated sodium channels. To find the primarily affected gene in
      Huntington's disease (HD) pathogenesis, we profiled HD transgenic mice using a
      high-density oligonucleotide array and identified beta4 as an expressed sequence
      tag (EST) that was significantly down-regulated in the striatum of HD model mice
      and patients. Reduction in beta4 started at a presymptomatic stage in HD mice,
      whereas other voltage-gated ion channel subunits were decreased later. In
      contrast, spinal cord neurons, which generate only negligible levels of expanded
      polyglutamine aggregates, maintained normal levels of beta4 expression even at
      the symptomatic stage. Overexpression of beta4 induced neurite outgrowth in
      Neuro2a cells, and caused a thickening of dendrites and increased density of
      dendritic spines in hippocampal primary neurons, indicating that beta4 modulates
      neurite outgrowth activities. These results suggest that down-regulation of beta4
      may lead to abnormalities of sodium channel and neurite degeneration in the
      striatum of HD transgenic mice and patients with HD.

PMID- 16805844
TI  - Increase of proliferating oligodendroglial progenitors in the adult mouse brain
      upon Sonic hedgehog delivery in the lateral ventricle.
AB  - Sonic hedgehog signaling is required for the maintenance of stem cell niches in
      the postnatal subventricular zone and the proliferation of neural progenitors in
      the mature hippocampus. We show here that delivery of Sonic hedgehog protein into
      the lateral ventricle of adult mice increases cell proliferation in the corpus
      callosum and cerebral cortex. In this latter area, the number of neural
      progenitors expressing the proteoglycan NG2 is enhanced 2 days after the
      injection. In both areas, mRNA up-regulation of the transcriptional target gene
      Patched was observed in cells expressing the oligodendroglial transcription
      factor Olig1. Twenty-six days following the adenovirus-mediated delivery of Sonic
      hedgehog into the lateral ventricle, newly generated cells in the cerebral cortex
      and in the corpus callosum are influenced towards the initial steps of
      oligodendrogenesis, as indicated by a 50% increase in the number of cells
      expressing the oligodendroglial marker DM20. Our experiments demonstrate that the
      number of oligodendrocyte precursor cells in the cerebral cortex and corpus
      callosum can be increased upon delivery of Sonic hedgehog proteins and highlight
      the potential capacity of the adult brain to mobilize a pool of premyelinating
      cells.

PMID- 16805845
TI  - Olfactory receptors and signalling elements in the Grueneberg ganglion.
AB  - The Grueneberg ganglion (GG) is a cluster of neurones present in the vestibule of
      the anterior nasal cavity. Although its function is still elusive, recent studies
      have shown that cells of the GG transcribe the gene encoding the olfactory marker
      protein (OMP) and project their axons to glomeruli of the olfactory bulb,
      suggesting that they may have a chemosensory function. Chemosensory
      responsiveness of olfactory neurones in the main olfactory epithelium (MOE) and
      the vomeronasal organ (VNO) is based on the expression of either odorant
      receptors or vomeronasal putative pheromone receptors. To scrutinize its
      presumptive olfactory nature, the GG was assessed for receptor expression by
      extensive RT-PCR analyses, leading to the identification of a distinct
      vomeronasal receptor which was expressed in the majority of OMP-positive GG
      neurones. Along with this receptor, these cells expressed the G proteins Go and
      Gi, both of which are also present in sensory neurones of the vomeronasal organ.
      Odorant receptors were expressed by very few cells during prenatal and perinatal
      stages; a similar number of cells expressed adenylyl cyclase type III and
      G(olf/s), characteristic signalling elements of the main olfactory system. The
      findings of the study support the notion that the GG is in fact a subunit of the
      complex olfactory system, comprising cells with either a VNO-like or a MOE-like
      phenotype. Moreover, expression of a vomeronasal receptor indicates that the GG
      might serve to detect pheromones.

PMID- 16805846
TI  - Transient glucose and amino acid deprivation induces delayed preconditioning in
      cultured rat cortical neurons.
AB  - Several studies have demonstrated that glucose deprivation, combined either with
      anoxia or with the inhibition of oxidative phosphorylation, leads to the
      development of ischemic tolerance in neurons. The aim of our experiments was to
      investigate whether similar effects could be achieved by transient energy
      deprivation without either anoxia or the inhibition of the electron transfer
      chain. Preconditioning was carried out by incubating primary rat cortical
      neuronal cultures for 3, 6 or 9 h in a glucose- and amino acid-free balanced salt
      solution supplemented with B27 in normoxic conditions. After 24 h, neuronal
      cultures were exposed to oxygen-glucose deprivation, glutamate or hydrogen
      peroxide. Cell viability was measured 24 h after the lethal insults. Potential
      mechanisms that can influence free radical production were also examined. Energy
      deprivation protected neuronal cells against lethal stimuli (e.g. cell survival
      after oxygen-glucose deprivation was 33.1 +/- 0.52% in the untreated group and
      80.1 +/- 1.27% in the 9-h energy deprivation group), reduced mitochondrial
      membrane potential, decreased free radical formation, attenuated the
      intracellular free calcium surge upon glutamate receptor stimulation, and
      resulted in an elevated level of GSH. Our findings show that transient energy
      deprivation induces delayed preconditioning and prevents oxidative injuries and
      neuronal cell death.

PMID- 16805847
TI  - Balance of purines may determine life or death of retinal ganglion cells as A3
      adenosine receptors prevent loss following P2X7 receptor stimulation.
AB  - The purines ATP and adenosine can act as a coordinated team of transmitters. As
      extracellular adenosine is frequently derived from the enzymatic
      dephosphorylation of released ATP, the distinct actions of the two purines can be
      synchronized. In retinal ganglion cells (RGCs), stimulation of the P2X7 receptor
      for ATP leads to increased intracellular Ca2+ and death. Here we define the
      contrasting effects of adenosine and identify protective actions mediated by the
      A3 receptor. Adenosine attenuated the rise in Ca2+ produced by the P2X7 agonist
      3'-O-(4-benzoylbenzoyl)ATP (BzATP). Adenosine was also neuroprotective,
      increasing the survival of ganglion cells exposed to BzATP. The A3 adenosine
      receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronimide (Cl-IB
      MECA) mimicked the inhibition of the Ca2+ rise, whereas the A3 antagonist 3-Ethyl
      5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5
      dicarboxylate (MRS-1191) reduced the protective effects of adenosine. Both Cl-IB
      MECA and a second A3 receptor agonist IB-MECA reduced the cell loss triggered by
      BzATP. The actions of BzATP were mimicked by ATPgammaS, but not by ATP. In
      summary, adenosine can stop the rise in Ca2+ and cell death resulting from
      stimulation of the P2X7 receptor on RGCs, with the A3 adenosine receptor
      contributing to this protection. Hydrolysis of ATP into adenosine and perhaps
      inosine shifts the balance of purinergic action from that of death to the
      preservation of life.

PMID- 16805848
TI  - Expanded polyglutamines impair synaptic transmission and ubiquitin-proteasome
      system in Caenorhabditis elegans.
AB  - Polyglutamine (polyQ) expansion in many proteins, including huntingtin and ataxin
      3, is pathogenic and responsible for neuronal dysfunction and degeneration.
      Although at least nine neurodegenerative diseases are caused by expanded polyQ,
      the pathogenesis of these diseases is still not well understood. In the present
      study, we used Caenorhabditis elegans to study the molecular mechanism of polyQ
      mediated toxicity. We expressed full-length and truncated ataxin-3 with different
      lengths of polyQ in the nervous system of C. elegans. We show that expanded polyQ
      interrupts synaptic transmission, and induces swelling and aberrant branching of
      neuronal processes. Using an ubiquitinated fluorescence reporter construct, we
      also showed that polyQ aggregates impair the ubiquitin-proteasome system in C.
      elegans. These results may provide information for further understanding the
      pathogenesis of polyQ diseases.

PMID- 16805849
TI  - Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are
      vulnerable to injury.
AB  - Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are widely
      expressed in the mammalian CNS, though their functional significance remains
      unclear. The corresponding null-knockout mutations are lethal. Here, we developed
      novel mutant mice in which the gene encoding the beta subunit of PDGFR (PDGFR
      beta) was genetically deleted in CNS neurons to elucidate the role of PDGFR-beta,
      particularly in the post-natal stage. Our mutant mice reached adulthood without
      apparent anatomical defects. In the mutant brain, immunohistochemical analyses
      showed that PDGFR-beta detected in neurons and in the cells in the subventricular
      zone of the lateral ventricle in wild-type mice was depleted, but PDGFR-beta
      detected in blood vessels remained unaffected. The cerebral damage after
      cryogenic injury was severely exacerbated in the mutants compared with controls.
      Furthermore, TdT-mediated dUTP-biotin nick end labeling (TUNEL)-positive neuronal
      cell death and lesion formation in the cerebral hemisphere were extensively
      exacerbated in our mutant mice after direct injection of NMDA without altered
      NMDA receptor expression. Our results clearly demonstrate that PDGFR-beta
      expressed in neurons protects them from cryogenic injury and NMDA-induced
      excitotoxicity.

PMID- 16805850
TI  - Comparison of the binding pockets of two chemically unrelated allosteric
      antagonists of the mGlu5 receptor and identification of crucial residues involved
      in the inverse agonism of MPEP.
AB  - Fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2
      yl)urea], a clinically validated non-benzodiazepine anxiolytic, has been shown to
      be a potent and non-competitive metabotropic glutamate (mGlu)-5 receptor
      antagonist. In the present study, we have used the site-directed mutagenesis
      coupled with three-dimensional receptor-based pharmacophore modelling to
      elucidate the interacting mode of fenobam within the seven-transmembrane domain
      (7TMD) of mGlu5 receptor and its comparison with that of 2-methyl-6
      (phenylethynyl)pyridine (MPEP), the prototype antagonist. The common residues
      involved in the recognition of MPEP and fenobam include Pro654(3.36),
      Tyr658(3.40), Thr780(6.44), Trp784(6.48), Phe787(6.51), Tyr791(6.55) and
      Ala809(7.47). The differentiating residues between both modulators' interacting
      modes are Arg647(3.29), Ser657(3.39) and Leu743(5.47). Our data suggest that
      these chemically unrelated mGlu5 antagonists act similarly, probing a
      functionally unique region of the 7TMD. Using [3H]inositol phosphates
      accumulation assay, we have also identified the critical residues involved in the
      inverse agonist effect of MPEP. The mutation W784(6.48)A completely blocked the
      inverse agonist activity of MPEP; two mutations F787(6.51)A and Y791(6.55)A,
      caused a drastic decrease in the MPEP inverse agonism. Furthermore, these three
      mutations led to an increased efficacy of quisqualate without having any effect
      on its potency. The fact that the residues Trp784(6.48) and Phe787(6.51) are
      essential equally in antagonism and inverse agonism effects emphasizes again the
      key role of these residues and the involvement of a common transmembrane network
      in receptor inactivation by MPEP.

PMID- 16805851
TI  - Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B
      adenosine receptors.
AB  - Caffeine, an unspecific antagonist of adenosine receptors, is commonly used to
      treat the apnea of prematurity. We have defined the effects of caffeine on the
      carotid body (CB) chemoreceptors, the main peripheral controllers of breathing,
      and identified the adenosine receptors involved. Caffeine inhibited basal (IC50,
      210 microm) and low intensity (PO2 approximately 66 mm Hg/30 mm K+) stimulation
      induced release of catecholamines from chemoreceptor cells in intact preparations
      of rat CB in vitro. Opposite to caffeine, 5'-(N-ethylcarboxamido)adenosine (NECA;
      an A2 agonist) augmented basal and low-intensity hypoxia-induced release. 2-p-(2
      Carboxyethyl)phenethyl-amino-5'-N-ethylcaboxamido-adenosine hydrochloride
      (CGS21680), 2-hexynyl-NECA (HE-NECA) and SCH58621 (A2A receptors agents) neither
      affected catecholamine release nor altered the caffeine effects. The 8-cycle-1,3
      dipropylxanthine (DPCPX; an A1/A2B antagonist) and 8-(4-{[(4
      cyanophenyl)carbamoylmethyl]-oxy}phenyl)-1,3-di(n-propyl)xanthine (MRS1754; an
      A2B antagonist) mimicking of caffeine indicated that caffeine effects are
      mediated by A2B receptors. Immunocytochemical A2B receptors were located in
      tyrosine hydroxylase positive chemoreceptor cells. Caffeine reduced by 52% the
      chemosensory discharges elicited by hypoxia in the carotid sinus nerve.
      Inhibition had two components with pharmacological analysis indicating that A2A
      and A2B receptors mediate, respectively, the low (17 x 10(-9) m) and high (160 x
      10(-6) m) IC50 effects. It is concluded that endogenous adenosine, via
      presynaptic A2B and postsynaptic A2A receptors, can exert excitatory effects on
      the overall output of the rat CB chemoreceptors.

PMID- 16805852
TI  - Modification by curcumin of mutagenic activation of carcinogenic N-nitrosamines
      by extrahepatic cytochromes P-450 2B1 and 2E1 in rats.
AB  - To elucidate the mechanism underlying suppression by curcumin of esophageal
      carcinogenesis induced by NMBA, we evaluated the CYP level and mutagenic
      activation of environmental carcinogens, by immunoblot analyses and Ames
      preincubation test, respectively, and bilirubin, 4-nitrophenol and testosterone
      UDPGT activities in F344 rats treated with curcumin and/or NMBA. No significant
      alterations in the hepatic levels of constitutive CYP proteins, mutagenic
      activation by liver S9 or hepatic UDPGT activities were produced by subcutaneous
      treatment with 0.5 mg/kg NMBA for 5 weeks and/or feeding of 0.05% and 0.2%
      curcumin for 6 weeks. In contrast, gavage of 0.2% curcumin decreased esophageal
      CYP2B1 and 2E1 by up to 60%, compared with vehicle control. Similarly,
      intragastric treatment with 270 mg/kg curcumin decreased esophageal and gastric
      CYP2B1 and CYP2E1, but not in lung, kidney or intestine. Conversely, large
      intestinal CYP2B1 was 2.8-fold higher in the treated rats than in control rats.
      Mutagenic activities of NOC, including NMBA, in the presence of esophagus and
      stomach S9 were markedly decreased in the treated rats, whereas those in the
      presence of large intestine S9 were 2.2-3.0-fold above control. These results
      show that modifying effects of curcumin on esophageal carcinogenesis can be
      attributed to a decrease in metabolic activation of NMBA by esophageal CYP2B1
      during the initiation phase, without the contribution of metabolic activation and
      inactivation by liver. Further, the present findings suggest the potential of
      curcumin for modification of gastric and intestinal carcinogenesis initiated with
      NOC.

PMID- 16805853
TI  - Melanosis and squamous cell neoplasms of the upper aerodigestive tract in
      Japanese alcoholic men.
AB  - Melanosis is frequently observed in the upper aerodigestive tract of Japanese
      alcoholic men, and the prevalences of squamous cell dysplasia and SCC in the
      upper aerodigestive tract of Japanese alcoholic men are high. This study
      evaluated associations between melanosis and both neoplasms of the upper
      aerodigestive tract and factors contributing to the development of melanosis in
      Japanese alcoholic men. Endoscopic screening of 643 Japanese alcoholic men (aged
      50-79 years) was combined with oropharyngolaryngeal inspection and esophageal
      iodine staining, and ALDH2 genotyping was carried out in 425 of them. Melanosis
      was frequently (20.8%) observed in the upper aerodigestive tract. The palate was
      the most common site of melanosis (11.2%), followed by the pharynx (9.5%), and by
      the esophagus (7.0%). The incidence of melanosis was higher in those with
      esophageal dysplasia (31/126, 24.6%), esophageal SCC (19/42, 45.2%), and
      oropharyngolaryngeal SCC (8/14, 54.1%) than in cancer- and dysplasia-free
      controls (69/437, 15.8%). The presence of melanosis was associated with a higher
      risk of esophageal dysplasia, esophageal SCC, and oropharyngolaryngeal SCC (OR
      1.69, 4.03, and 6.61, respectively). Multivariate analysis showed that older age,
      heavier smoking, and heterozygosity for inactive ALDH2 were positively associated
      with the presence of melanosis. The presence of melanosis indicates a high risk
      for neoplasms in the upper aerodigestive tract of Japanese alcoholic men.
      Melanosis and neoplasms have the same causes, including older age, heavy smoking,
      and high acetaldehyde exposure.

PMID- 16805854
TI  - Natural killer T cell-mediated antitumor immune responses and their clinical
      applications.
AB  - A unique lymphocyte population, CD1d-restricted NKT cells, has been revealed to
      be a key player in both the innate and acquired immune responses, including
      antitumor effects. Recent studies revealed that at least two subsets of CD1d
      restricted NKT cells exist: type I, having invariant Valpha14 receptor; and type
      II, having heterogeneous non-Valpha14 receptor. The specific glycolipid ligand,
      alpha-GalCer, effectively stimulates mouse and human type I NKT cells. The
      activation of type I NKT cells substantially influences function of other various
      cell types, particularly DC, NK cells, CD4 Th1 cells, and CD8 cytotoxic T cells,
      all contributing to the antitumor immune responses. Recent studies also indicated
      that, unlike type I NKT cells, type II NKT cells have a potential to repress
      antitumor immune responses. In this review, we summarize the characteristics of
      the antitumor immune responses mediated by both mouse and human CD1d-restricted
      NKT cells and discuss their potential in clinical applications against cancer.

PMID- 16805855
TI  - Rapid induction of skin tumors in human but not mouse c-Ha-ras proto-oncogene
      transgenic mice by chemical carcinogenesis.
AB  - The rasH2 transgenic mice carry human c-Ha-ras proto-oncogene, and are highly
      susceptible to chemical carcinogenesis. Previous studies showed that the mutation
      of c-Ha-ras induced by DMBA in the tumors of rasH2 were detected only in
      transgenes. To examine if the difference between the codons of the c-Ha-ras gene
      in human and mouse contributed to the tissue-specific sensitivity to DMBA, we
      generated a line of transgenic mice, mras, carrying mouse c-Ha-ras genome with
      its own promoter. Western blot analysis showed that the protein expression of H
      RAS in the skin was increased in both rasH2 and mras compared with wild-type.
      Chemical skin carcinogenesis was induced by DMBA and TPA. In rasH2 mice, the
      latency of tumor formation was shorter than wild-type littermates. Both the
      number and the volume of skin tumors were increased in rasH2 than those of wild
      type. However, in mras mice, enhancement of tumor formation was not observed as
      compared with wild-type. The mean number of tumors and the latency of tumor
      development was almost the same between mras and wild-type littermates.
      Mutational analysis showed only A to T transversion in human c-Ha-ras transgenes
      at codon 61 but not in murine endogenous c-Ha-ras gene in the tumors of rasH2. In
      the tumors of wild-type littermates and mras, A to T transversion in murine c-Ha
      ras at codon 61 were detected. These results indicate that the differences in the
      codon of the c-Ha-ras gene between mouse and human might contribute to the tissue
      specific sensitivity of DMBA.

PMID- 16805856
TI  - Age-specific hormonal decline is accompanied by transcriptional changes in human
      sebocytes in vitro.
AB  - The importance of hormones in endogenous aging has been displayed by recent
      studies performed on animal models and humans. To decipher the molecular
      mechanisms involved in aging we maintained human sebocytes at defined hormone
      substituted conditions that corresponded to average serum levels of females from
      20 (f20) to 60 (f60) years of age. The corresponding hormone receptor expression
      was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR),
      Western blotting and immunocytochemistry. Cells at f60 produced significantly
      lower lipids than at f20. Increased mRNA and protein levels of c-Myc and
      increased protein levels of FN1, which have been associated with aging, were
      detected in SZ95 sebocytes at f60 compared to those detected at f20 after 5 days
      of treatment. Expression profiling employing a cDNA microarray composed of 15 529
      cDNAs identified 899 genes with altered expression levels at f20 vs. f60.
      Confirmation of gene regulation was performed by real-time RT-PCR. The functional
      annotation of these genes according to the Gene Ontology identified pathways
      related to mitochondrial function, oxidative stress, ubiquitin-mediated
      proteolysis, cell cycle, immune responses, steroid biosynthesis and phospholipid
      degradation - all hallmarks of aging. Twenty-five genes in common with those
      identified in aging kidneys and several genes involved in neurodegenerative
      diseases were also detected. This is the first report describing the
      transcriptome of human sebocytes and its modification by a cocktail of hormones
      administered in age-specific levels and provides an in vitro model system, which
      approximates some of the hormone-dependent changes in gene transcription that
      occur during aging in humans.

PMID- 16805857
TI  - Coagulation defects in cirrhosis--old dogmas not yet ready for burial.

PMID- 16805858
TI  - Aprotinin is useful as a hemostatic agent in cardiopulmonary surgery: yes.

PMID- 16805859
TI  - Megakaryocyte polyploidization is associated with decreased expression of polo
      like kinase (PLK).
AB  - BACKGROUND: During differentiation, megakaryocytes (MK), the bone marrow
      precursors of circulating blood platelets, undergo polyploidization, repeated
      rounds of DNA replication without cell division. Mature normal MK may contain a
      DNA content of up to 128N, in contrast to normal diploid (2N) cells. The extent
      of polyploidy may influence the number of platelets produced by the MK.
      Therefore, understanding the molecular mechanisms regulating polyploidization
      could identify events involved in controlling both cell division and
      thrombopoiesis. OBJECTIVE: We investigated the expression of several proteins
      involved in mitosis in cultured mouse MK, and tested the effect of expression on
      polyploidization. METHODS: Western blot and immunofluorescent analyses were used
      to assess expression of cell cycle proteins in cultured MK. Populations of
      polyploidizing MK were separated on the basis of DNA content by flow cytometry.
      The gene encoding mouse polo-like kinase 1 (PLK-1) was introduced into MK by
      retroviral transduction, and its effects measured by flow cytometry. RESULTS:
      Polyploid mouse MK expressed lower levels of two proteins, p55CDC and PLK-1,
      whose activity is necessary for cell cycle progression and completion of mitosis.
      Comparison of sorted 2N/4N and polyploid MK indicated that PLK-1 expression was
      absent in polyploid MK, while expression of other cell cycle proteins was similar
      in both populations. Forced expression of PLK-1 during MK differentiation was
      associated with decreased polyploidization. CONCLUSION: These experiments suggest
      that PLK-1 is an important regulator of polyploidization in differentiating MK.

PMID- 16805860
TI  - von Willebrand factor A1 domain can adequately substitute for A3 domain in
      recruitment of flowing platelets to collagen.
AB  - BACKGROUND: Binding of von Willebrand factor (VWF) to platelet GPIbalpha and to
      collagen is attributed to VWF A1 and A3 domains, respectively. OBJECTIVES: Using
      VWF, VWF lacking A1 (DeltaA1-VWF) or A3 (DeltaA3-VWF) and VWF with defective A3
      (H1786A-VWF), in combination with recombinant A1 (residues 1262-1492) or A3
      (residues 1671-1878), fused to glutathione-S-transferase (GST-A1 and GST-A3), we
      have re-investigated the role of A1 in platelet recruitment to surfaces of
      collagen. METHODS AND RESULTS: In flow, measurable binding of DeltaA3-VWF
      occurred to horse tendon, but also to human type III collagen. GST-A1 and GST-A3
      both competed for binding of DeltaA1-VWF and DeltaA3-VWF to horse tendon collagen
      fibrils in static conditions and to human collagen III during plasmon surface
      resonance studies, substantiating overlapping binding sites on both collagens for
      A1 and A3. Heparin did not affect A3-mediated binding of VWF and DeltaA1-VWF, but
      inhibited binding to horse tendon collagen of GST-A1 and DeltaA3-VWF.
      Furthermore, A1-mediated binding to type III collagen of DeltaA3-VWF binding was
      strongly salt-sensitive. During perfusions at wall shear rate 2500 s(-1) of
      calcein-labeled platelets in reconstituted blood, DeltaA3-VWF and H1786A-VWF
      triggered platelet binding to horse tendon collagen comparably and as potently as
      VWF, and to human type III collagen, only fivefold less potently, DeltaA1-VWF
      being inactive. Additional flow-controlled interaction studies with DeltaA3-VWF,
      H1786A-VWF, the collagen-VWF antagonist saratin, heparin and the VWF neutralizing
      antibody 82D6A3 confirmed that H1786A-VWF binds to collagen exclusively via A1.
      CONCLUSION: Hence, in shear forces the VWF A1 domain can assume the role of A3 to
      trigger substantial platelet recruitment to human collagen fibres.

PMID- 16805861
TI  - Effects of monetary reward and punishment on stimulus-preceding negativity.
AB  - This study examined the effects of emotional valence on stimulus-preceding
      negativity (SPN) using reward and fine. A time estimation task under reward,
      punishment, combined, and control conditions was performed. Participants were
      rewarded for accurate responses in the reward condition, and were fined for
      incorrect estimations in the punishment condition. in the combined condition,
      correct responses were rewarded and incorrect responses were fined. In the
      control condition, neither a reward nor fine was used. Results showed a
      significant interaction of condition x hemisphere. The SPN at the left hemisphere
      was increased in the reward condition. For the punishment effect, although it
      evoked right hemisphere dominance, no conditional difference was apparent at the
      right hemisphere. These results suggest that the SPN is affected by positive
      emotion: The left hemisphere activation might represent a pleasant emotion
      accompanying monetary gain.

PMID- 16805862
TI  - ERP/CSD indices of impaired verbal working memory subprocesses in schizophrenia.
AB  - To disentangle subprocesses of verbal working memory deficits in schizophrenia,
      long EEG epochs (>10 s) were recorded from 13 patients and 17 healthy adults
      during a visual word serial position test. ERP generator patterns were summarized
      by temporal PCA from reference-free current source density (CSD) waveforms to
      sharpen 31-channel topographies. Patients showed poorer performance and reduced
      left inferior parietotemporal P3 source. Build-up of mid-frontal negative slow
      wave (SW) in controls during item encoding, integration, and active maintenance
      was absent in patients, whereas a sustained mid-frontal SW sink during the
      retention interval was comparable across groups. Mid-frontal SW sinks (encoding
      and retention periods) and posterior SW sinks and sources (encoding only) were
      related to performance in controls only. Data suggest disturbed processes in a
      frontal-parietotemporal network in schizophrenia, affecting encoding and early
      item storage.

PMID- 16805863
TI  - Beware misleading cues: perceptual similarity modulates the N2/P3 complex.
AB  - Event-related potentials were used to investigate neural processes relating
      perceptual similarity to action control. To assess whether perceptual overlap
      among targets and nontargets would modulate the N2/P3 complex, the present study
      used multiple nontarget categories varying in their targetlike characteristics.
      Participants made one (relatively rare) response to a low-probability stimulus
      (target), and they made a different (relatively common) response to all other
      stimuli (nontargets). The critical nontarget categories had equivalent
      probability (.10) but varied in their targetlike characteristics. Supporting the
      N2 component as sensitive to the strength of conflicting action imperatives,
      perceptual overlap among targets and nontargets elicited a prominent N2. In
      contrast, amplitude of the P3 component appeared most sensitive to the extent of
      cognitive processing needed for categorization.

PMID- 16805864
TI  - Age and novelty: event-related brain potentials and autonomic activity.
AB  - Our aim was to study age-related differences in the habituation of orienting
      reaction by using novel visual stimuli. We intended to fill a gap in habituation
      research by recording both autonomic and ERP components of orienting to visual
      stimuli in the same sample and in highly related paradigms. We report data
      showing that in young subjects repetition of visual novels yielded fast
      habituation of both skin conductance responses and ERP components (P3(novel),
      N2b) whereas elderly people displayed no sign of habituation. However, cardiac
      deceleration--thought conventionally to be part of the orienting reaction--did
      not habituate in either group. Overall, most of our results harmonize with those
      obtained by using auditory stimuli; therefore we conclude that there is no
      significant modality specificity in age-related deterioration of habituation
      processes.

PMID- 16805865
TI  - Pre-attentive representation of sound duration in the human brain.
AB  - Studies using a brain index for pre-attentive change detection, the mismatch
      negativity (MMN), suggested distinct neuronal populations for signaling changes
      in sound duration and frequency. However, these studies used only durations
      within the temporal window of loudness summation (ca. 200 ms) in which any
      duration change is accompanied by a loudness change. Hence, the present study
      employed stimulus durations both beyond and within this temporal window in order
      to examine the genuine duration representation in the brain. Magnetic mismatch
      responses (MMNm) for duration and frequency changes were compared with each
      other. The equivalent current dipole (ECD) of the duration MMNm was located in
      the auditory cortex slightly posterior to that for the frequency MMNm
      irrespective of stimulus duration. The results suggested separate memory
      representations for sound duration and frequency in the human brain.

PMID- 16805866
TI  - Electrophysiological support for strategic processing of spatial sentences.
AB  - The aims of the present EEG study were to distinguish between the various
      representation options of spatial sentences and to gain insight into the moment
      at which differences in the processing of spatial sentences arise. To examine the
      possible existence of different strategies, we used sentence-sentence and
      sentence-picture verification trials in mixed blocks, whereby the probability of
      a specific second stimulus was fixed within a block but varied between blocks.
      Brain activation (slow wave, 550-1100 ms after stimulus onset) linked to parsing
      spatial sentences (and not nonspatial sentences) occurred at parieto-occipital
      regions associated with mental image processing, and only when participants were
      expecting to compare verbal information to a picture. Therefore, this study
      provides neuroimaging evidence that different representational formats of spatial
      sentences arise almost directly when people are reading a spatial sentence.

PMID- 16805867
TI  - Musical training and language-related brain electrical activity in children.
AB  - This experiment aimed at testing whether 8 weeks of musical training affect the
      ability of 8-year-old children to detect pitch changes in language. Twenty
      nonmusician children listened to linguistic phrases that ended with prosodically
      congruous words or with weak or strong pitch incongruities. We recorded reaction
      times, error rates, and event-related brain potentials to the final words. Half
      of the children followed music training and the other half painting training, and
      all children were retested following training. For both groups, the weak
      incongruity was the most difficult to detect, but performance was not
      significantly different between groups. However, the amplitude of a late positive
      component was largest to strong incongruities and was reduced after training only
      in the music group. These results suggest that a relatively short exposure to
      pitch processing in music exerts some influence on pitch processing in language.

PMID- 16805868
TI  - Intentional modulation of emotional responding to unpleasant pictures: an ERP
      study.
AB  - Intentionally altering responses to unpleasant stimuli affects physiological and
      hemodynamic activity associated with emotional and cognitive processing. In the
      present experiment, we measured the late-positive potential (LPP) of the visually
      evoked event-related brain potential to examine the effects of intentional
      emotion modulation on electrophysiological correlates of emotional and cognitive
      processing. Seventeen participants received instructions to view, suppress, and
      enhance emotional responses to unpleasant stimuli. Results revealed significantly
      decreased electrophysiological activity during suppression of emotional responses
      beginning around 250 ms poststimulus and lasting several hundred milliseconds.
      These data suggest that ERPs are sensitive to emotion modulation/regulation
      processes.

PMID- 16805869
TI  - Diurnal variation of the startle reflex in relation to HPA-axis activity in
      humans.
AB  - Diurnal variation of baseline startle amplitude was examined in 14 normal
      inpatients on a research unit where behavioral activity and environmental stimuli
      were highly controlled. We tested a hypothesized association between diurnal
      variations of salivary cortisol and reflex amplitude by recording acoustic
      startle eyeblinks shortly before bedtime, when cortisol was near its lowest daily
      level, and just after awakening, when cortisol was at its peak. Results showed
      that startle eyeblinks were greater during evening than morning sessions, whereas
      the opposite was true for cortisol levels. Skin conductance levels and reaction
      time performance also increased from morning to evening. These findings are
      consistent with accumulating evidence suggesting a possible link between startle
      reactivity and hypothalamic-pituitary-adrenal axis activity, and an association
      between diurnal variations in endogenous arousal and startle amplitude.

PMID- 16805870
TI  - The antisaccade task as a research tool in psychopathology: a critical review.
AB  - The antisaccade task is a measure of volitional control of behavior sensitive to
      fronto-striatal dysfunction. Here we outline important issues concerning
      antisaccade methodology, consider recent evidence of the cognitive processes and
      neural mechanisms involved in task performance, and review how the task has been
      applied to study psychopathology. We conclude that the task yields reliable and
      sensitive measures of the processes involved in resolving the conflict between
      volitional and reflexive behavioral responses, a key cognitive deficit relevant
      to a number of neuropsychiatric conditions. Additionally, antisaccade deficits
      may reflect genetic liability for schizophrenia. Finally, the ease and accuracy
      with which the task can be administered, combined with its sensitivity to fronto
      striatal dysfunction and the availability of suitable control conditions, may
      make it a useful benchmark tool for studies of potential cognitive enhancers.

PMID- 16805871
TI  - Systolic inhibition of nociceptive responding is moderated by arousal.
AB  - Inhibition of the nociceptive flexion reflex during systole could be due to
      activation of the arterial baroreceptors. Physiological arousal, characterized by
      raised blood pressure, increases afferent activity from the arterial
      baroreceptors but attenuates the baroreflex. This study examined the effects of
      arousal on systolic inhibition of the nociceptive flexion reflex in 38 adults.
      The threshold current to elicit the reflex in the leg was determined, and
      participants were stimulated at threshold intensity for 12 trials in two
      conditions: rest (low arousal) and mental arithmetic (high arousal). In each
      trial, stimulation was delivered 0 ms, 300 ms, or 600 ms after the R-wave of the
      electrocardiogram. Nociceptive responding was inhibited for stimulation at 300 ms
      after the R-wave during rest but not mental arithmetic. This moderation of
      systolic inhibition of nociception could be due to attenuation of the baroreflex
      with increased arousal.

PMID- 16805872
TI  - P50 sensitivity to physical and psychological state influences.
AB  - Although P50 is described as a largely preattentive process, increasing evidence
      suggests that the psychological state of a participant may influence P50 and its
      suppression. A paired-stimulus paradigm was used to examine the contributions of
      variability in stimulus parameters and state factors, such as expectancy and
      vigilance, on P50. Results obtained from 34 healthy subjects indicate that
      stimulus intensity and background stimulus intensity influenced P50 amplitude
      whereas stimulus duration had no significant impact. Importantly, P50 suppression
      varied with fluctuations in P50 amplitude to the first stimulus, and both P50 and
      its suppression reflected possible declines in attention or vigilance over the
      course of the session. Findings from this study suggest that P50 is not entirely
      preattentional and may reflect the psychological state of a participant.
      Implications of these results for research with schizophrenia patients are
      discussed.

PMID- 16805873
TI  - Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis
      during endotoxemia in rats.
AB  - BACKGROUND: Sepsis and endotoxemia are associated with concurrent activation of
      inflammation and the hemostatic mechanism, which both contribute to organ
      dysfunction and death. Electrical vagus nerve stimulation (VNS) has been found to
      inhibit tumor necrosis factor (TNF)-alpha release during endotoxemia in rodents.
      OBJECTIVE: To determine the effect of VNS on activation of coagulation and
      fibrinolysis. METHODS: Rats received a sublethal i.v. dose of lipopolysaccharide
      (LPS) after electrical VNS or sham stimulation. Activation of coagulation and
      fibrinolysis, as well as cytokine release, was measured before LPS injection and
      2, 4 and 6 h thereafter. RESULTS: LPS induced activation of the coagulation
      system (increases in the plasma concentrations of thrombin-antithrombin complexes
      and D-dimer, and a decrease in antithrombin) and biphasic changes in the
      fibrinolytic system [early rises of plasminogen activator activity and tissue
      type plasminogen activator, followed by a delayed increase in plasminogen
      activator inhibitor type 1 (PAI-1)]. VNS strongly inhibited all LPS-induced
      procoagulant responses and more modestly attenuated the fibrinolytic response. In
      addition, VNS attenuated the LPS-induced increases in plasma and splenic
      concentrations of the proinflammatory cytokines TNF-alpha and interleukin-6 (IL
      6), while not influencing the release of the anti-inflammatory cytokine IL-10.
      CONCLUSION: These data illustrate a thus far unrecognized effect of VNS and
      suggest that the cholinergic anti-inflammatory pathway not only impacts on
      inflammation but also on the coagulant-anticoagulant balance.

PMID- 16805874
TI  - Female hemophilia A heterozygous for a de novo frameshift and a novel missense
      mutation of factor VIII.
AB  - BACKGROUND: Hemophilia A (HA) is an X-chromosome-linked recessive disorder. AIM:
      We report the case of a female HA patient with a moderate decrease of factor (F)
      VIII activity and antigen (FVIII:C 3.4%, FVIII:Ag 4.2%) and severe bleeding
      symptoms. METHODS: The patient's father had mild FVIII deficiency (FVIII:C 6.9%,
      FVIII:Ag 7.4%), and her mother had normal FVIII activity. The von Willebrand
      disease antigen and von Willebrand factor ristocetin cofactor activity were
      normal in all family members. The genomic DNA was extracted from the peripheral
      blood lymphocytes of the patient and her family members. Long-distance polymerase
      chain reaction (PCR) was employed to screen for the intron 22 inversion of the
      FVIII coding gene (F8). The F8 coding sequence was amplified with PCR and
      sequenced with an automatic sequencer. RESULTS: Two heterozygous mutations were
      identified in the patient: one a substitution of nucleotide 5981T by C that leads
      to a missense mutation Leu1975Pro, and the other an insertion of an 'A' between
      nucleotides 3,637 and 3,638 (3637_3638insA) that shifts the reading frame and
      predicts a premature stop codon downward. The mutation Leu1975Pro was identified
      in the father's F8; however, 3637_3638insA was a de novo mutation that occurred
      in the patient's maternal-derived F8. Real-time PCR was applied to analyze the
      level of ectopically F8 gene transcripts in the peripheral lymphocytes of family
      members. The ectopic transcripts of F8 of the patient were less abundant than the
      normal control (patient:normal control ratio 0.67), whereas her parents showed no
      significant difference from the normal control. CONCLUSION: The FVIII deficiency
      of the HA patient resulted from a de novo occurrence of a frameshift
      3637_3638insA in her maternal-derived F8 and a novel missense mutation Leu1975Pro
      inherited from her father.

PMID- 16805876
TI  - FIELD study.

PMID- 16805877
TI  - The implications of the renal NSF for diabetologists.

PMID- 16805878
TI  - The metabolic syndrome: 'to be or not to be, that is the question.

PMID- 16805879
TI  - Foot infection.

PMID- 16805880
TI  - Hyperosmolar hyperglycaemic syndrome.

PMID- 16805881
TI  - The International Quotidian Dialysis Registry: annual report 2006.
AB  - Interest in short daily and nocturnal hemodialysis (HD) regimens continues to
      grow worldwide. Despite growing optimism that these therapies will afford better
      patient outcomes over conventional HD, the current literature has not been viewed
      as sufficiently compelling to affect widespread implementation in most
      jurisdictions. Before these therapies can gain wider acceptance, larger and more
      rigorous studies will likely be needed. In June 2004, the Quotidian Dialysis
      Registry, based at the Lawson Health Research Institute at the University of
      Western Ontario, Canada, began recruiting patients across North America. By using
      an Internet-based data entry platform, patients from various centers worldwide
      will eventually be recruited, and studied prospectively. This paper constitutes
      the second annual update on patient and center recruitment, patient and treatment
      characteristics, and future directions for the registry.

PMID- 16805882
TI  - Phosphate binders: new products and challenges.
AB  - Optimal phosphate control in dialysis patients is extremely challenging. A
      growing awareness of the deleterious effect of mineral metabolism imbalances
      together with the lack of a satisfactory explanation for the exaggerated
      mortality rate in patients undergoing renal replacement therapy has led to a
      renewed effort to refine our approach to hyperphosphatemia. However, despite the
      remarkable improvements in dialysis techniques, phosphate control has not
      substantially improved. Achieving normo-phosphatemia presents a multitude of
      practical and scientific challenges related to the optimal target level,
      cardiovascular health, and drug toxicities. It is the aim of the present review
      to summarize briefly the controversies associated with currently available
      phosphate binders, a cornerstone in the current management of hyperphosphatemia.

PMID- 16805883
TI  - Heparin-induced thrombocytopenia: an uncommon but serious complication of heparin
      use in renal replacement therapy.
AB  - Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially life
      threatening complication of heparin therapy. Hemodialysis and hemofiltration
      patients are regularly exposed to heparin, which is used for extracorporeal
      anticoagulation. Type II HIT (HIT-II) is the rarer immune-mediated form and is of
      huge clinical significance. The clinical manifestation of HIT-II is
      characteristically with venous and arterial thrombotic events. However, systemic
      and pulmonary reactions have been reported. Type II HIT is due to antibodies to
      the heparin-platelet factor 4 complex, which induce a cascade of events leading
      to thrombocytopenia and thrombosis. Nowadays, with increasing availability of
      functional and immunoassay tests for HIT-associated antibodies, HIT diagnosis can
      be confirmed more readily. Hence, it is important to rapidly recognize, diagnose,
      and manage this syndrome early in hemodialysis patients with thrombocytopenia to
      avoid serious consequences resulting in morbidity and mortality. We report a case
      of HIT-II manifesting atypically as a "pseudopulmonary embolus" in a hemodialysis
      patient and discuss the clinical management of HIT.

PMID- 16805884
TI  - Management of hypertension in hemodialysis patients.
AB  - The relationship of hypertension with adverse outcomes is uncertain in the
      hemodialysis population. If hypertension is an etiologically significant
      cardiovascular risk factor in hemodialysis patients, the first step would be to
      assess the level of BP accurately. BP obtained at home over a week and averaged
      using a validated oscillometric automatic device can prove valuable. To the
      extent BP lowering influences cardiovascular outcomes, home BP of 150/90 mm Hg
      would warrant therapy, since it correlates with target organ damage and
      hypertension diagnosed by ambulatory BP monitoring. To manage hypertension,
      limiting dietary sodium intake and individualizing dialysate sodium delivery
      would be first steps. The magnitude of reduction in BP with dietary sodium
      restriction and the whether dialysate sodium can be safely limited in those who
      are hypotension-prone is unclear. Antihypertensive drug therapies can effectively
      reduce BP and are needed by the vast majority of hemodialysis patients. Whether
      control of hypertension translates into better outcomes is not known, but
      collective evidence suggests that hypertension should be controlled in
      hemodialysis patients.

PMID- 16805885
TI  - Changing patterns of pericardial disease in patients with end-stage renal
      disease.
AB  - Pericarditis can occur in patients with chronic renal failure before initiation
      of dialysis. It is also described in established dialysis patients.
      Traditionally, the cause of pericarditis in such settings has been attributed to
      uremia and/or inadequate dialysis and it is consequently thought that
      intensifying the dialysis process in such patients could improve outcome. We
      report here 7 cases of acute pericarditis in patients with end-stage renal
      disease on renal replacement therapy. Only 3 of the patients gave any history of
      chest pain, and a pericardial friction rub was only noted in 2. Despite a period
      of intensive dialysis, none of the patients improved and all required pericardial
      drainage as the definitive curative procedure. The clinical presentation of acute
      pericarditis in dialysis patients therefore may be atypical and pericardial
      drainage should be considered early, as intensive dialysis alone may not lead to
      resolution.

PMID- 16805886
TI  - Acute hemolysis with acute renal failure in a patient with valproic acid
      poisoning treated with charcoal hemoperfusion.
AB  - Hemoperfusion consists of the passage of anticoagulated blood through a column
      containing adsorbent particles. It was introduced in 1940 and refined from 1950
      to 1970, and then introduced clinically for the treatment of acute intoxications
      between 1970 and 1980. Life-threatening valproic acid toxicity is an indication
      for coated charcoal hemoperfusion usually accomplished without complications, but
      we report a case of acute severe intravascular hemolysis during the time of
      hemoperfusion with coated charcoal column.

PMID- 16805887
TI  - Physical disability, psychological status, and health-related quality of life in
      older hemodialysis patients and age-matched controls.
AB  - We aimed at comparing the elderly adults and normal subjects with regard to their
      disability, psychological status, and quality of life (QOL). One hundred and
      twenty-five dialysis patients and 61 controls were recruited in the study.
      Depression and anxiety symptoms of the patients were evaluated with the
      Psychological Symptom Screening List (SCL 90-R). For evaluating the disability,
      the Rivermead mobility index (RMI) was utilized. For evaluating the QOL, we used
      the short form-36 (SF-36) scale. The Rivermead mobility index of the patients
      (9.6 +/- 3.4) was found. When compared with controls, dialysis patients had
      higher levels of disability (p = 0.0001). Depression and anxiety symptom scores
      of these patients were also significantly higher than that of the controls (p <
      0.05). There was a correlation between the disability and depression symptom
      scores (r: 0.171, p = 0.037). Both physical and mental capacity scores of the
      dialysis patients were lower than those of the controls (p < 0.05 and p < 0.05)
      QOL scores for elderly hemodialysis patients were found to be lower. Their
      disability was higher, making them dependable on others during their daily lives.
      Specific exercise programs should be developed for these patients. Even the
      smallest effort in this regard will result in improvements in physical
      functioning while bringing them significant benefits.

PMID- 16805888
TI  - Effect of improvement in anemia on electroneurophysiological markers (P300) of
      cognitive dysfunction in chronic kidney disease.
AB  - Our aim is to study the effect of improvement in anemia on event-related
      potentials (ERPs; P300) as markers of cognitive dysfunction in predialysis and
      dialysis patients of chronic kidney disease (CKD). Thirty anemic patients of CKD
      (hemoglobin [Hb] < 9 g%), 15 in the predialysis group (Group A), and 15 patients
      on biweekly hemodialysis (Group B) were recruited for the study. Patients of
      uremic encephalopathy, dyselectrolytemia, and those with hearing problems were
      excluded. Both groups were given recombinant human erythropoietin (rhuEPO) 100
      IU/kg biweekly for 6 weeks by the subcutaneous route. No intervention was
      performed in the third control group (Group C), which consisted of 30 normal
      healthy volunteers. The improvement in Hb was assessed every 2 weeks, and the
      amplitude and latency of the P300 component of the ERPs were studied before
      initiating treatment and after 6 weeks of rhuEPO administration. There was a
      significant increase in Hb in both the study groups without any significant
      alteration in kidney functions. A significant reduction in P300 latency was noted
      in both the study groups after intervention. Similarly, the amplitude of P300
      also increased in both study groups, but attained statistical significance for
      the dialysis group only. No significant changes were observed in the control
      group. Administration of EPO in patients of anemia with CKD resulted in a
      significant improvement in the electrophysiological markers of cognitive function
      in the form of increased amplitudes and decreased latencies of P300 in both
      predialysis and dialysis patients.

PMID- 16805889
TI  - Quality of life in chronic hemodialysis patients in Russia.
AB  - The aim of this cross-sectional study was to compare health-related quality of
      life (HRQOL) of Russian hemodialysis (HD) patients with the general population
      and international data, and to determine factors influencing HRQOL. One thousand
      forty-seven HD patients from 6 dialysis centers were studied (576 male, age 43.5
      +/- 12.5 years, HD duration 55.0 +/- 47.2 months). Health-related quality of life
      was evaluated by SF-36. Self-appraisal Depression Scale (W. Zung), State-Trait
      Anxiety Inventory, and Level of Neurotic Asthenia Scale were used. Hemodialysis
      patients scored significantly lower than the general Russian population in the
      majority of SF-36 scales. The only exception was the Mental Health score, which
      was even better than the general population. The Mean physical component score
      (PCS) of HD patients was 36.9 +/- 9.7, and the mental component score was (MCS)
      44.2 +/- 10.5. In multiple linear regression analysis, increasing age, HD
      duration, depression level and number of days of hospitalization in the past 6
      months were significant independent predictors of low PCS along with a low level
      of serum albumin. Advancing age was also a predictive factor for low MCS along
      with increase of HD duration, depression level, trait anxiety, and level of
      asthenia. As far as we know, this is the first study to report on HRQOL of a
      large sample of Russian HD patients performed using SF-36. Compared with the
      general population, Russian HD patients had significantly lower scores on the
      majority of SF-36 scales, especially in the physical domain. The mean PCS and MCS
      were comparable with European data for HD patients. A number of demographic,
      clinical, and psychological variables affect HRQOL.

PMID- 16805890
TI  - Calcium phosphate metabolism and bone mineral density with nocturnal
      hemodialysis.
AB  - An elevated calcium x phosphate product (Ca x P) is an independent risk factor
      for vascular calcification and cardiovascular death in dialysis patients. More
      physiological dialysis in patients undergoing nocturnal hemodialysis (NHD) has
      been shown to produce biochemical advantages compared with conventional
      hemodialysis (CHD) including superior phosphate (P) control. Benefits of
      dialysate with greater calcium (Ca) concentration are also reported in NHD to
      prevent Ca depletion and subsequent hyperparathyroidism, but there are concerns
      that a higher dialysate Ca concentration may contribute to raised serum Ca levels
      and greater Ca x P and vascular disease. The NHD program at our unit has been
      established for 4 years, and we retrospectively analyzed Ca and P metabolism in
      patients undergoing NHD (8-9 h/night, 6 nights/week). Our cohort consists of 11
      patients, mean age 49.3 years, who had been on NHD for a minimum of 12 months,
      mean 34.3 months. Commencement was with low-flux (LF) NHD and 1.5 mmol/L Ca
      dialysate concentration, with conversion to high-flux (HF) dialyzers after a
      period (mean duration 18.7 months). We compared predialysis serum albumin, intact
      parathyroid hormone, P, total corrected Ca, and Ca x P at baseline on CHD, after
      conversion to LF NHD and during HF NHD. We also prospectively measured bone
      mineral density (BMD) on all patients entering the NHD program. Bone densitometry
      (DEXA) scans were performed at baseline (on CHD) and yearly after commencement of
      NHD. With the introduction of HF dialyzers, the Ca dialysate concentration was
      concurrently raised to 1.75 mmol/L after demonstration on DEXA scans of worsening
      osteopenia. Analysis of BMD, for all parameters, revealed a decrease over the
      first 12 to 24 months (N = 11). When the dialysate Ca bath was increased, the
      median T and Z scores subsequently increased (data at 3 years, N = 6). The mean
      predialysis P levels were significantly lower on LF NHD vs. CHD (1.51 vs. 1.77
      mmol/L, p = 0.014), while on HF NHD P was lower again (1.33 mmol/L, p = 0.001 vs.
      CHD). Predialysis Ca levels decreased with conversion from CHD to LF NHD (2.58
      vs. 2.47 mmol/L, p = 0.018) using a 1.5 mmol/L dialysate Ca concentration. The
      mean Ca x P on CHD was 4.56 compared with a significant reduction of 3.74 on LF
      NHD (p = 0.006) and 3.28 on HF NHD (p = 0.001 vs. CHD), despite the higher
      dialysate Ca in the latter. We conclude that an elevated dialysate Ca
      concentration is required to prevent osteopenia. With concerns that prolonged
      higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca
      dialysate bath is still unknown. Better P control on NHD, however, reduces the
      overall Ca x P, despite the increased Ca concentration, therefore reducing the
      risk of vascular calcification.

PMID- 16805891
TI  - Cardiac response to hemodialysis with different cardiovascular tolerance: heart
      rate variability and QT interval analysis.
AB  - A therapy-specific worsening of cardiovascular stability during bicarbonate
      dialysis (BD) with respect to acetate-free biofiltration (AFB) have been
      previously reported. We further investigated the impact of the 2 therapies on
      electrocardiographic parameters in order to gain novel insight into the cardiac
      responses. Holter ECG acquired during hypotension-free sessions (12 BD + 12 AFB)
      were retrospectively analyzed. R-R intervals were extracted from ECG recordings.
      An autoregressive spectral technique was used to compute low- and high-frequency
      (LF and HF) components of heart rate variability (HRV). QT interval duration was
      measured with a computer-assisted technique and corrected for HR. In BD the LF
      component of HRV after an initial increase was slowly depressed with respect to
      AFB (p < 0.05). QT duration showed a significant (p < 0.01) hemodialysis-induced
      reduction. QT shortening was more pronounced (p < 0.05) in BD than in AFB (-31
      vs. -10 ms), even after correction for HR (p < 0.05). Cardiac electrical activity
      is significantly affected by the hemodialysis technique. The decrease in the LF
      component of HRV and the QT shortening are coherent with the worse cardiovascular
      tolerance observed in BD and with the hypothesis of an enhanced production of
      endogenous nitric oxide.

PMID- 16805892
TI  - Clinical characteristics and outcomes of new uremic patients with extreme
      azotemia in southern Taiwan.
AB  - Serum creatinine (SCr) had been considered to be an important predictor of
      mortality in end-stage renal disease (ESRD) patients at the start of renal
      replacement therapy (RRT). However, the data were limited about initially extreme
      azotemia (EA), exclusively defined as blood urea nitrogen (BUN) > or = 300 mg/dL,
      SCr > or = 30 mg/dL, or both. This retrospective study was conducted to clarify
      the characteristics and outcome in our EA patients. We had 1682 new ESRD patients
      from July 1988 to December 1996. With frequency match for age, gender, and
      starting RRT in the same period, 20 EA patients and 60 controls were included.
      Fifty percent of our EA patients had unknown etiology. The EA patients had
      significantly lower prevalence of underlying diabetic nephropathy, and comorbid
      hypertension. All the EA patients had late referral to nephrologists within 4
      weeks before the initiation of RRT, and 90% of them had taken Chinese herbals.
      The EA group had significantly higher BUN, SCr, and iron storage as well as a
      higher prevalence of severe anemia, hyperkalemia, hypocalcemia, and acidemia.
      However, the similar prevalence of cardiomegaly and left ventricular hypertrophy
      as well as the similar early mortality rate and long-term survival were noted.
      Age over 40 years, comorbid diabetes mellitus, and hypoalbuminemia were
      independent predictors of poor survival. Our EA patients had different initial
      presentations from other uremic ones at the start of RRT. However, the short-term
      and long-term mortality rates were similar. The lower prevalence of underlying
      diabetic nephropathy and comorbid hypertension among the EA patients might
      contribute to their fair outcome.

PMID- 16805893
TI  - Progressive resistance training during hemodialysis: rationale and method of a
      randomized-controlled trial.
AB  - Skeletal muscle wasting in patients receiving maintenance hemodialysis (HD) has
      been well documented. The rationale for prescribing progressive resistance
      training (PRT) in this cohort in an attempt to reverse this catabolism and induce
      a wide spectrum of physiological, functional, and psychological health-related
      adaptations is extremely strong. Unfortunately, the barriers to exercise adoption
      in this cohort are many, which may explain the persisting sedentariness of this
      population and the lack of widespread clinical programs such as are now
      commonplace in cardiac rehabilitation and pulmonary rehabilitation units. Current
      health care practices for HD patients do not address the negative health issues
      of inactivity and muscle wasting. Therefore, we conducted the first randomized
      controlled trial to prescribe PRT during maintenance HD treatment. The purpose of
      this paper is to present the rationale and methodology that we utilized for
      implementing intradialytic PRT in a conventional outpatient HD clinic. Potential
      areas for modification of PRT regimens in this setting are also presented.

PMID- 16805894
TI  - Comment on factors influencing low-molecular-weight solute clearance during
      hemodialysis.

PMID- 16805896
TI  - Can you spare a dime to buy Darwin a cup of coffee?

PMID- 16805897
TI  - Origin of planktotrophy--evidence from early molluscs.
AB  - The size of early ontogenetic shells (protoconchs) of ancient benthic molluscs
      suggests that feeding larvae occurred at about 490 myr (approximately, transition
      from Cambrian to Ordovician). Most studied Ordovician protoconchs were smaller
      than Cambrian ones, indicating smaller Ordovician eggs and hatchlings. This
      suggests substitution of nutritious reserve matter such as yolk by plankton as an
      energy source for larvae. The observed size change represents the first direct
      empiric evidence for a late Cambrian to Ordovician switch to planktotrophy in
      invertebrate larvae. It corroborates previous hypotheses about a possible
      polyphyly of planktotrophy. These hypotheses were primarily based on molecular
      clock data of extant clades with different types of larva, change in the overall
      body size, as well as increasing predation pressure on Early Paleozoic sea
      floors. The Early Ordovician is characterized by an explosive radiation of
      benthic suspension feeders and it was suggested that planktotrophy would
      prolongate escape from benthic predation on hatchlings. This biological
      escalation hypothesis does not fully explain why planktotrophy and suspension
      feeding became important at the same time, during a major biodiversification. An
      additional factor that probably included availability of nutrients must have
      played a role. We speculate that an increasing nutrient supply and availability
      of photoautotrophic plankton in world oceans have facilitated both planktotrophy
      and suspension feeding, which does not exclude a contemporaneous predation-driven
      escalation. It is very likely that the evolution of planktotrophy as well as
      increasing predation contributed to the Ordovician radiation.

PMID- 16805898
TI  - Developmental plasticity and disparity in early dipnoan (lungfish) dentitions.
AB  - Although the lungfish (Dipnoi) belong within the Osteichthyes, their dentitions
      are radically different from other osteichthyans. Lungfish dentitions also show a
      uniquely high structural disparity during the early evolution of the group,
      partly owing to the independent variation of odontogenic and odontoclastic
      processes that are tightly and stereotypically coordinated in other
      osteichthyans. We present a phylogenetic analysis of early lungfishes
      incorporating a novel approach to coding these process characters in preference
      to the resultant adult dental morphology. The results only partially resolve the
      interrelationships of Devonian dipnoans, but show that the widely discussed
      hypothesis of separate tooth-plated, dentine-plated, and denticulated lineages is
      unlikely to be true. The dipnoan status of Diabolepis is corroborated. Lungfish
      dentitions seem to have undergone extensive and nonparsimonious evolution during
      the early history of the group, but much of the resulting disparity can be
      explained by a modest number of evolutionary steps in the underlying
      developmental processes, those for dental formation (odontogenic) and those for
      the remodeling of dentine tissue (odontoclastic). Later in lungfish evolution,
      this disparity was lost as the group settled to a pattern of dental development
      that is just as stereotypic as, but completely different from, that of other
      osteichthyans.

PMID- 16805899
TI  - Evolution of the class III HD-Zip gene family in land plants.
AB  - Arabidopsis class III homeodomain-leucine zipper (HD-Zip III) proteins play
      overlapping, distinct, and antagonistic roles in key aspects of development that
      have evolved during land plant evolution. To better understand this gene family's
      role in plant evolution and development as well as to address broader questions
      of how duplicated genes functionally diversify, we investigated the evolutionary
      history of this gene family. Phylogenetic analyses including homologs from
      diverse land plants indicate that a gene duplication event before the angiosperm-
      gymnosperm split gave rise to two gene lineages that diversified during
      angiosperm plant radiation. Heterologous expression of an HD-Zip III gene from
      the nonvascular plant moss within the Arabidopsis HD-zip III revoluta mutant
      modified but did not complement the phenotype. Comparison of the expression
      domains of flowering and nonflowering plant homologs indicate an ancestral role
      in vascular development and organ initiation but not in specifying organ
      polarity, a prominent role for angiosperm homologs.

PMID- 16805900
TI  - Different roads to form the same gut in nematodes.
AB  - The morphogenesis of a gut from the endoderm has been well studied among the
      animal kingdom and is also well described in the nematode Caenorhabditis elegans.
      But are there other ways to build a nematode intestine? Sulston et al. (1983)
      described a different intestinal cell lineage in the species Panagrellus
      redivivus and Turbatrix aceti that includes two programmed cell deaths. However,
      no details are known about the three-dimensional (3D) configuration and the role
      of the cell deaths. Here, we describe the intestinal morphogenesis of P.
      redivivus and five other nematode species by means of four-dimensional
      microscopy, which gives us a 3D representation of gut formation at the cellular
      level. The morphological pathway of gut formation is highly conserved among these
      distantly related species. However, we found the P. redivivus pattern in another
      related species Halicephalobus gingivalis. In this pattern, the intestinal
      precursors migrate inward in concert with the mesoderm precursors. Based on the
      observations, we propose a hypothesis that could explain the differences. The
      positions of the mesoderm precursors create a possible spatial constraint, by
      which the establishment of bilateral symmetry in the intestine is delayed. This
      symmetry is corrected by cell migrations; other cells are eliminated and
      compensated by supplementary cell divisions. This pattern leads to the same
      result as in the other nematodes: a bilateral symmetrical intestine with nine
      rings. This illustrates how conserved body plans can be achieved by different
      developmental mechanisms.

PMID- 16805901
TI  - Molecular evolution of fibrillar collagen in chordates, with implications for the
      evolution of vertebrate skeletons and chordate phylogeny.
AB  - Vertebrates have seven types of fibrillar collagens that are encoded by 11 genes.
      Types I, V, and XXIV collagens are components of mineralized bone, whereas types
      II, XI, and XXVII collagens are components of cartilage. In this study, we traced
      the molecular evolutionary history of chordate collagen genes and examined how
      gene duplications gave rise to the collagen genes used for skeletons. Our
      analyses of deuterostome collagen genes, including one amphioxus gene that we
      identified in this study, suggest that the common ancestors of deuterostomes
      possessed three fibrillar collagen genes. Expression analyses of chordate
      fibrillar collagen genes suggest that in the ancestors of chordates, fibrillar
      collagen was co-opted to the formation of the notochord sheath independently in
      three clades. Our results also imply that co-option of collagen genes to
      cartilage occurred in clade A (col2A1), clade B (col11A1, 11A2), and clade C
      (COL27A1). Similarly, some fibrillar collagen genes have been co-opted for
      mineralized bone independently from clade A genes (col1A1, 1A2, 5A2), clade B
      genes (col5A1), and clade C genes (COL24A1). These frequent co-options for
      notochord, cartilage, and mineralized bone must have been accompanied by the
      rapid evolution of cis-regulatory elements for transcription. In addition, we
      found that one of the ascidian fibrillar collagen genes possesses an amino acid
      insertion at the identical site of the C-terminal noncollagenous domain in
      vertebrate fibrillar collagen genes. This observation raises a suspicion about
      the relatively well-accepted phylogeny of the close relationship between
      amphioxus and vertebrates.

PMID- 16805902
TI  - A model for the morphogenesis of strip reduction patterns in phototrophic
      euglenids: evidence for heterochrony in pellicle evolution.
AB  - We propose a general developmental model that explains the evolutionary origin,
      diversification, and inheritance of pellicle strip patterns in phototrophic
      euglenids. Dividing cells of Euglena gracilis, E. viridis, and Phacus similis
      were observed with scanning electron microscopy in order to study the
      morphogenesis of posterior whorls of strip reduction. We found evidence that
      constant whorl numbers are maintained through cell division because of organized
      strip growth before and during cytokinesis. Alternating nascent strips form a new
      whorl of strip reduction at each of the anterior and posterior ends of daughter
      cells. Strips that terminated to form posterior whorls in the mother cell change
      in length during the development of daughter cells. In the mother cells of E.
      gracilis, the strips forming whorls I and II grow to become whorls II and III,
      respectively, in the daughter cells; the strips forming whorl III in the mother
      cell lengthen and meet with other strips already present at the posterior tip of
      daughter cells. This process of whorl morphogenesis during asexual reproduction
      is consistent with known variation in pellicle strip patterns and suggests that
      heterochrony played a major role in the ultrastructural evolution of phototrophic
      euglenids.

PMID- 16805904
TI  - Is there gold at the top of the beanstalk?
AB  - A report on the 3rd International Legume Genetics and Genomics Conference,
      Brisbane, Australia, 9-13 April 2006.

PMID- 16805905
TI  - The RNA interference pathway: a new target for autoimmunity.
AB  - Many intracellular macromolecular complexes that are involved in the production
      or degradation of RNAs are targeted by autoantibodies in systemic autoimmune
      diseases. RNA interference (RNAi) is a recently characterized gene silencing
      pathway by which specific mRNAs are either degraded or translationally
      suppressed. In a recent issue of Arthritis Research and Therapy, Andrew Jakymiw
      and colleagues reported that the enigmatic Su autoantigen complex contains key
      components of the RNAi machinery. Anti-Su autoantibodies from both human patients
      with rheumatic diseases and a mouse model of autoimmunity recognize the
      endonucleolytic Argonaute and Dicer proteins, both crucial enzymes of the RNAi
      pathway. These data raise the question of how the anti-Su response is triggered.
      So far, it is unknown whether molecular modifications may be involved, as has
      been proposed for other intracellular autoantigens. The implication of RNAi in
      anti-viral defence may suggest a role for virus infection in this process.

PMID- 16805906
TI  - Identification of arthritis-related gene clusters by microarray analysis of two
      independent mouse models for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of
      the population worldwide. Previously, we showed that human T-cell leukemia virus
      type I-transgenic mice and interleukin-1 receptor antagonist-knockout mice
      develop autoimmunity and joint-specific inflammation that resembles human RA. To
      identify genes involved in the pathogenesis of arthritis, we analyzed the gene
      expression profiles of these animal models by using high-density oligonucleotide
      arrays. We found 1,467 genes that were differentially expressed from the normal
      control mice by greater than threefold in one of these animal models. The gene
      expression profiles of the two models correlated well. We extracted 554 genes
      whose expression significantly changed in both models, assuming that
      pathogenically important genes at the effector phase would change in both models.
      Then, each of these commonly changed genes was mapped into the whole genome in a
      scale of the 1-megabase pairs. We found that the transcriptome map of these genes
      did not distribute evenly on the chromosome but formed clusters. These identified
      gene clusters include the major histocompatibility complex class I and class II
      genes, complement genes, and chemokine genes, which are well known to be involved
      in the pathogenesis of RA at the effector phase. The activation of these gene
      clusters suggests that antigen presentation and lymphocyte chemotaxis are
      important for the development of arthritis. Moreover, by searching for such
      clusters, we could detect genes with marginal expression changes. These gene
      clusters include schlafen and membrane-spanning four-domains subfamily A genes
      whose function in arthritis has not yet been determined. Thus, by combining two
      etiologically different RA models, we succeeded in efficiently extracting genes
      functioning in the development of arthritis at the effector phase. Furthermore,
      we demonstrated that identification of gene clusters by transcriptome mapping is
      a useful way to find potentially pathogenic genes among genes whose expression
      change is only marginal.

PMID- 16805907
TI  - Cross sectional study of performance indicators for English Primary Care Trusts:
      testing construct validity and identifying explanatory variables.
AB  - BACKGROUND: The performance of Primary Care Trusts in England is assessed and
      published using a number of different performance indicators. Our study has two
      broad purposes. Firstly, to find out whether pairs of indicators that purport to
      measure similar aspects of quality are correlated (as would be expected if they
      are both valid measures of the same construct). Secondly, we wanted to find out
      whether broad (global) indicators correlated with any particular features of
      Primary Care Trusts, such as expenditure per capita. METHODS: Cross sectional
      quantitative analysis using data from six 2004/05 PCT performance indicators for
      303 English Primary Care Trusts from four sources in the public domain: Star
      Rating, aggregated Quality and Outcomes Framework scores, Dr Foster mortality
      index, Dr Foster equity index (heart by-pass and hip replacements), NHS
      Litigation Authority Risk Management standards and Patient Satisfaction scores
      from the Star Ratings. Forward stepwise multiple regression analysis to determine
      the effect of Primary Care Trust characteristics on performance. RESULTS: Star
      Rating and Quality and Outcomes Framework total, both summary measures of global
      quality, were not correlated with each other (F = 0.66, p = 0.57). There were
      however positive correlations between Quality and Outcomes Framework total and
      patient satisfaction (r = 0.61, p < 0.001) and between screening/'additional
      services' indicators on the Star Ratings and Quality and Outcomes Framework (F =
      24, p < 0.001). There was no correlation between different measures of access to
      services. Likewise we found no relationship between either Star Rating or
      Litigation Authority Standards and hospital mortality (F = 0.61, p = 0.61; F =
      0.31, p = 0.73). CONCLUSION: Performance assessment in healthcare remains on the
      Government's agenda, with new core and developmental standards set to replace the
      Star Ratings in 2006. Yet the results of this analysis provide little evidence
      that the current indicators have sufficient construct validity to measure the
      underlying concept of quality, except when the specific area of screening is
      considered.

PMID- 16805909
TI  - Validating the Johns Hopkins ACG Case-Mix System of the elderly in Swedish
      primary health care.
AB  - BACKGROUND: Individualbased measures for comorbidity are of increasing importance
      for planning and funding health care services. No measurement for individualbased
      healthcare costs exist in Sweden. The aim of this study was to validate the Johns
      Hopkins ACG Case-Mix System's predictive value of polypharmacy (regular use of 4
      or more prescription medicines) used as a proxy for health care costs in an
      elderly population and to study if the prediction could be improved by adding
      variables from a population based study i.e. level of education, functional
      status indicators and health perception. METHODS: The Johns Hopkins ACG Case-Mix
      System was applied to primary health care diagnoses of 1402 participants (60-96
      years) in a cross-sectional community based study in Karlskrona, Sweden (the
      Swedish National study on Ageing and Care) during a period of two years before
      they took part in the study. The predictive value of the Johns Hopkins ACG Case
      Mix System was modeled against the regular use of 4 or more prescription
      medicines, also using age, sex, level of education, instrumental activity of
      daily living- and measures of health perception as covariates. RESULTS: In an
      exploratory biplot analysis the Johns Hopkins ACG Case-Mix System, was shown to
      explain a large part of the variance for regular use of 4 or more prescription
      medicines. The sensitivity of the prediction was 31.9%, whereas the specificity
      was 88.5%, when the Johns Hopkins ACG Case-Mix System was adjusted for age. By
      adding covariates to the model the sensitivity was increased to 46.3%, with a
      specificity of 90.1%. This increased the number of correctly classified by 5.6%
      and the area under the curve by 11.1%. CONCLUSION: The Johns Hopkins ACG Case-Mix
      System is an important factor in measuring comorbidity, however it does not
      reflect an individual's capability to function despite a disease burden, which
      has importance for prediction of comorbidity. In this study we have shown that
      information on such factors, which can be obtained from short questionnaires
      increases the probability to correctly predict an individual's use of resources,
      such as medications.

PMID- 16805910
TI  - Pelvic floor muscle training and adjunctive therapies for the treatment of stress
      urinary incontinence in women: a systematic review.
AB  - BACKGROUND: Stress urinary incontinence (SUI) is a prevalent and costly condition
      which may be treated surgically or by physical therapy. The aim of this review
      was to systematically assess the literature and present the best available
      evidence for the efficacy and effectiveness of pelvic floor muscle training
      (PFMT) performed alone and together with adjunctive therapies (eg biofeedback,
      electrical stimulation, vaginal cones) for the treatment of female SUI. METHODS:
      All major electronic sources of relevant information were systematically searched
      to identify peer-reviewed English language abstracts or papers published between
      1995 and 2005. Randomised controlled trials (RCTs) and other study designs eg non
      randomised trials, cohort studies, case series, were considered for this review
      in order to source all the available evidence relevant to clinical practice.
      Studies of adult women with a urodynamic or clinical diagnosis of SUI were
      eligible for inclusion. Excluded were studies of women who were pregnant,
      immediately post-partum or with a diagnosis of mixed or urge incontinence.
      Studies with a PFMT protocol alone and in combination with adjunctive physical
      therapies were considered. Two independent reviewers assessed the eligibility of
      each study, its level of evidence and the methodological quality. Due to the
      heterogeneity of study designs, the results are presented in narrative format.
      RESULTS: Twenty four studies, including 17 RCTs and seven non-RCTs, met the
      inclusion criteria. The methodological quality of the studies varied but lower
      quality scores did not necessarily indicate studies from lower levels of
      evidence. This review found consistent evidence from a number of high quality
      RCTs that PFMT alone and in combination with adjunctive therapies is effective
      treatment for women with SUI with rates of 'cure' and 'cure/improvement' up to
      73% and 97% respectively. The contribution of adjunctive therapies is unclear and
      there is limited evidence about treatment outcomes in primary care settings.
      CONCLUSION: There is strong evidence for the efficacy of physical therapy for the
      treatment for SUI in women but further high quality studies are needed to
      evaluate the optimal treatment programs and training protocols in subgroups of
      women and their effectiveness in clinical practice.

PMID- 16805911
TI  - Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal
      antibody, CMA-676, Mylotarg) in children with relapsed/refractory myeloid
      leukemia.
AB  - BACKGROUND: Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal
      antibody that has given promising preliminary results in adult myeloid CD33+ AML.
      We conducted a retrospective multicenter study of 12 children treated with GO on
      a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were
      refractory to first-line treatment, 8 patients with de novo AML were in
      refractory first relapse, and one patient with de novo AML was in 2nd relapse
      after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases.
      METHODS: GO was administered alone, at a unit dose of 3-9 mg/m2, once (3
      patients), twice (3 patients), three (5 patients) or five times (1 patient). Mean
      follow-up was 128 days (8-585 d). RESULTS: There were three complete responses
      (25%) leading to further curative treatment (SCT). Treatment failed in the other
      nine patients, and only one patient was alive at the end of follow-up. NCI-CTC
      grade III/IV adverse events comprised hematological toxicity (n = 12),
      hypertransaminasemia (n = 2), allergy and hyperbilirubinemia (1 case each). There
      was only one major adverse event (grade IV allergy). No case of sinusoidal
      obstruction syndrome occurred. CONCLUSION: These results warrant a prospective
      trial of GO in a larger population of children with AML.

PMID- 16805912
TI  - A randomized controlled trial of a psychoeducational group program for unipolar
      depression in adults in Norway (NCT00319540).
AB  - BACKGROUND: Coping with Depression Course (CWD) has shown to be effective in the
      treatment of depression. However, there are very few randomized controlled trials
      on unipolar depression in adults. AIMS: To test the effect of a modified CWD on
      unipolar depression in a randomized controlled trial design in adults. METHODS:
      Participants were recruited through mass media, tested by BDI and clinical
      interview, and randomized into intervention group (N = 81) and control group (N =
      74). The program was mainly conducted by nurses with background in psychiatry and
      primary health care, and the intervention encompassed 8 weekly sessions of 2 1/2
      hours, with 3 booster sessions. RESULTS: By "intention-to-treat" analysis a
      statistically significant effect on depressive symptoms at follow up at 6 months
      was found, and the level of symptoms was sustained after 12 months. CONCLUSION:
      The study shows that the intervention is effective in the treatment of unipolar
      depression, and suitable for specialized psychiatric services as well as primary
      health care.

PMID- 16805913
TI  - Identification and characterization of Smyd2: a split SET/MYND domain-containing
      histone H3 lysine 36-specific methyltransferase that interacts with the Sin3
      histone deacetylase complex.
AB  - BACKGROUND: Disrupting the balance of histone lysine methylation alters the
      expression of genes involved in tumorigenesis including proto-oncogenes and cell
      cycle regulators. Methylation of lysine residues is commonly catalyzed by a
      family of proteins that contain the SET domain. Here, we report the
      identification and characterization of the SET domain-containing protein, Smyd2.
      RESULTS: Smyd2 mRNA is most highly expressed in heart and brain tissue, as
      demonstrated by northern analysis and in situ hybridization. Over-expressed Smyd2
      localizes to the cytoplasm and the nucleus in 293T cells. Although accumulating
      evidence suggests that methylation of histone 3, lysine 36 (H3K36) is associated
      with actively transcribed genes, we show that the SET domain of Smyd2 mediates
      H3K36 dimethylation and that Smyd2 represses transcription from an SV40
      luciferase reporter. Smyd2 associates specifically with the Sin3A histone
      deacetylase complex, which was recently linked to H3K36 methylation within the
      coding regions of active genes in yeast. Finally, we report that exogenous
      expression of Smyd2 suppresses cell proliferation. CONCLUSION: We propose that
      Sin3A-mediated deacetylation within the coding regions of active genes is
      directly linked to the histone methyltransferase activity of Smyd2. Moreover,
      Smyd2 appears to restrain cell proliferation, likely through direct modulation of
      chromatin structure.

PMID- 16805914
TI  - Raman spectroscopy: the gateway into tomorrow's virology.
AB  - In the molecular world, researchers act as detectives working hard to unravel the
      mysteries surrounding cells. One of the researchers' greatest tools in this
      endeavor has been Raman spectroscopy. Raman spectroscopy is a spectroscopic
      technique that measures the unique Raman spectra for every type of biological
      molecule. As such, Raman spectroscopy has the potential to provide scientists
      with a library of spectra that can be used to unravel the makeup of an unknown
      molecule. However, this technique is limited in that it is not able to manipulate
      particular structures without disturbing their unique environment. Recently, a
      novel technology that combines Raman spectroscopy with optical tweezers, termed
      Raman tweezers, evades this problem due to its ability to manipulate a sample
      without physical contact. As such, Raman tweezers has the potential to become an
      incredibly effective diagnostic tool for differentially distinguishing tissue,
      and therefore holds great promise in the field of virology for distinguishing
      between various virally infected cells. This review provides an introduction for
      a virologist into the world of spectroscopy and explores many of the potential
      applications of Raman tweezers in virology.

PMID- 16805916
TI  - Three options for citation tracking: Google Scholar, Scopus and Web of Science.
AB  - BACKGROUND: Researchers turn to citation tracking to find the most influential
      articles for a particular topic and to see how often their own published papers
      are cited. For years researchers looking for this type of information had only
      one resource to consult: the Web of Science from Thomson Scientific. In 2004 two
      competitors emerged--Scopus from Elsevier and Google Scholar from Google. The
      research reported here uses citation analysis in an observational study examining
      these three databases; comparing citation counts for articles from two
      disciplines (oncology and condensed matter physics) and two years (1993 and 2003)
      to test the hypothesis that the different scholarly publication coverage provided
      by the three search tools will lead to different citation counts from each.
      METHODS: Eleven journal titles with varying impact factors were selected from
      each discipline (oncology and condensed matter physics) using the Journal
      Citation Reports (JCR). All articles published in the selected titles were
      retrieved for the years 1993 and 2003, and a stratified random sample of articles
      was chosen, resulting in four sets of articles. During the week of November 7-12,
      2005, the citation counts for each research article were extracted from the three
      sources. The actual citing references for a subset of the articles published in
      2003 were also gathered from each of the three sources. RESULTS: For oncology
      1993 Web of Science returned the highest average number of citations, 45.3.
      Scopus returned the highest average number of citations (8.9) for oncology 2003.
      Web of Science returned the highest number of citations for condensed matter
      physics 1993 and 2003 (22.5 and 3.9 respectively). The data showed a significant
      difference in the mean citation rates between all pairs of resources except
      between Google Scholar and Scopus for condensed matter physics 2003. For articles
      published in 2003 Google Scholar returned the largest amount of unique citing
      material for oncology and Web of Science returned the most for condensed matter
      physics. CONCLUSION: This study did not identify any one of these three resources
      as the answer to all citation tracking needs. Scopus showed strength in providing
      citing literature for current (2003) oncology articles, while Web of Science
      produced more citing material for 2003 and 1993 condensed matter physics, and
      1993 oncology articles. All three tools returned some unique material. Our data
      indicate that the question of which tool provides the most complete set of citing
      literature may depend on the subject and publication year of a given article.

PMID- 16805915
TI  - Molecular signatures induced by interleukin-2 on peripheral blood mononuclear
      cells and T cell subsets.
AB  - Experimentally, interleukin-2 (IL-2) exerts complex immunological functions
      promoting the proliferation, survival and activation of T cells on one hand and
      inducing immune regulatory mechanisms on the other. This complexity results from
      a cross talk among immune cells which sways the effects of IL-2 according to the
      experimental or clinical condition tested. Recombinant IL-2 (rIL-2) stimulation
      of peripheral blood mononuclear cells (PBMC) from 47 donors of different genetic
      background induced generalized T cell activation and anti-apoptotic effects. Most
      effects were dependent upon interactions among immune cells. Specialized
      functions of CD4 and CD8 T cells were less dependent upon and often dampened by
      the presence of other PBMC populations. In particular, cytotoxic T cell effector
      function was variably affected with a component strictly dependent upon the
      direct stimulation of CD8 T cells in the absence of other PBMC. This observation
      may provide a roadmap for the interpretation of the discrepant biological
      activities of rIL-2 observed in distinct pathological conditions or treatment
      modalities.

PMID- 16805917
TI  - Is there a role of statins in the prevention of aortic biological prostheses
      degeneration.
AB  - It has been recently observed that statins might slow the progression of aortic
      stenosis or sclerosis. Preliminary reports suggested a similar positive effect in
      reducing the degeneration of aortic valve bioprostheses even though this
      hypothesis should be further proven and supported by new data. In this review the
      present evidences of the possible effects of statins in this field are discussed.

PMID- 16805918
TI  - SUMO: regulating the regulator.
AB  - Post-translational modifiers of the SUMO (Small Ubiquitin-related Modifier)
      family have emerged as key regulators of protein function and fate. While the
      past few years have seen an enormous increase in knowledge on SUMO enzymes,
      substrates, and consequences of modification, regulation of SUMO conjugation is
      far from being understood. This brief review will provide an overview on recent
      advances concerning (i) the interplay between sumoylation and other post
      translational modifications at the level of individual targets and (ii) global
      regulation of SUMO conjugation and deconjugation.

PMID- 16805919
TI  - Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen
      B27 Caucasian populations.
AB  - Killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen
      (HLA) loci are both highly polymorphic, and some HLA class I molecules bind and
      trigger cell-surface receptors specified by KIR genes. We examined whether the
      combination of KIR3DS1/3DL1 genes in concert with HLA-B27 genotypes is associated
      with susceptibility to ankylosing spondylitis (AS). Two HLA-B27-positive
      Caucasian populations were selected, one from Spain (71 patients and 105
      controls) and another from the Azores (Portugal) (55 patients and 75 controls).
      All were typed for HLA-B and KIR (3DS1 and 3DL1) genes. Our results show that in
      addition to B27, the allele 3DS1 is associated with AS compared with B27 controls
      (p < 0.0001 and p < 0.003 in the Spanish population and Azoreans, respectively).
      We also observed that the association of KIR3DS1 to AS was found in combination
      with HLA-B alleles carrying Bw4-I80 in trans position in the Spanish population
      (30.9% in AS versus 15.2% in B27 controls, p = 0.02, odds ratio (OR) = 2.49) and
      in Azoreans (27.2% in AS versus 8.7% in B27 controls, p = 0.01, OR = 4.4 in
      Azoreans). On the other hand, 3DL1 was decreased in patients compared with B27
      controls (p < 0.0001 in the Spanish population and p < 0.003 in Azoreans). The
      presence of this allele in combination with Bw4-I80 had a protective effect
      against the development of AS in the Spanish population (19.7% in AS, 35.2% in
      B27 controls; p = 0.03, OR = 0.45). The presence of KIR3DS1 or KIR3DL1 in
      combination with HLA-B*27s/HLA-B Bw4-I80 genotypes may modulate the development
      of AS. The susceptibility to AS could be determined by the overall balance of
      activating and inhibitory composite KIR-HLA genotypes.

PMID- 16805920
TI  - Nongenomic oestrogen signalling in oestrogen receptor negative breast cancer
      cells: a role for the angiotensin II receptor AT1.
AB  - INTRODUCTION: Oestrogens can mediate some of their cell survival properties
      through a nongenomic mechanism that involves the mitogen-activated protein kinase
      (MAPK) pathway. The mechanism of this rapid signalling and its dependence on a
      membrane bound oestrogen receptor (ER), however, remains controversial. The role
      of G-protein-coupled receptor and epidermal growth factor (EGF) receptor in an ER
      independent signalling pathway modulated by oestrogen was investigated. METHODS:
      ER-positive and ER-negative breast cancer cell lines (MCF-7 and SKBR3) and
      primary breast cancer cell cultures were used in this study. Cell proliferation
      was assessed using standard MTT assays. Protein and cAMP levels were detected by
      Western blotting and ELISA, respectively. Antigen localization was performed by
      immunocytochemistry, immunohistochemistry and immunofluorescence. Protein
      knockdown was achieved using small interfering RNA technologies. RESULTS: EGF and
      oestrogen, alone and in combination, induced cell proliferation and
      phosphorylation of MAPK proteins Raf and ERK (extracellular signal regulated
      kinase)1/2 in both ER-negative SKBR3 and ER-positive MCF-7 human breast cancer
      cell lines. Increased Raf phosphorylation was also observed in primary human
      breast cultures derived from ER-positive and ER-negative breast tumours.
      Oestrogen induced an increase in intracellular cAMP in ER-negative SKBR3 human
      breast cancer cells. Oestrogen-mediated cell growth and phosphorylation of MAPK
      was modified by the EGF receptor antagonist AG1478, the G-protein antagonist
      pertussis toxin, and the angiotensin II receptor antagonist saralasin. Knockdown
      of angiotensin II type 1 receptor (AT1) protein expression with small interfering
      RNA attenuated oestrogen-induced Raf phosphorylation in ER-negative cells. AT1
      receptor was found to be expressed in the cell membrane of breast tumour
      epithelial cells. CONCLUSION: These findings provide evidence that, in breast
      cancer cells, oestrogen can signal through AT1 to activate early cell survival
      mechanisms in an ER-independent manner.

PMID- 16805921
TI  - ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell
      signaling differentially.
AB  - BACKGROUND: The mitogen-activated protein (MAP) kinases p44ERK1 and p42ERK2 are
      crucial components of the regulatory machinery underlying normal and malignant
      cell proliferation. A currently accepted model maintains that ERK1 and ERK2 are
      regulated similarly and contribute to intracellular signaling by phosphorylating
      a largely common subset of substrates, both in the cytosol and in the nucleus.
      RESULTS: Here, we show that ablation of ERK1 in mouse embryo fibroblasts and NIH
      3T3 cells by gene targeting and RNA interference results in an enhancement of
      ERK2-dependent signaling and in a significant growth advantage. By contrast,
      knockdown of ERK2 almost completely abolishes normal and Ras-dependent cell
      proliferation. Ectopic expression of ERK1 but not of ERK2 in NIH 3T3 cells
      inhibits oncogenic Ras-mediated proliferation and colony formation. These
      phenotypes are independent of the kinase activity of ERK1, as expression of a
      catalytically inactive form of ERK1 is equally effective. Finally, ectopic
      expression of ERK1 but not ERK2 is sufficient to attenuate Ras-dependent tumor
      formation in nude mice. CONCLUSION: These results reveal an unexpected interplay
      between ERK1 and ERK2 in transducing Ras-dependent cell signaling and
      proliferation. Whereas ERK2 seems to have a positive role in controlling normal
      and Ras-dependent cell proliferation, ERK1 probably affects the overall signaling
      output of the cell by antagonizing ERK2 activity.

PMID- 16805922
TI  - Pro-adrenomedullin to predict severity and outcome in community-acquired
      pneumonia [ISRCTN04176397].
AB  - INTRODUCTION: Pro-adrenomedullin (proADM) is helpful for individual risk
      assessment and outcome prediction in sepsis. A major cause of sepsis is community
      acquired pneumonia (CAP). The aim of this study was to investigate the value of
      proADM levels for severity assessment and outcome prediction in CAP. METHODS:
      Data from 302 patients admitted to the emergency department with CAP were
      included in a prospective observational study. Procalcitonin, C-reactive protein
      levels, leukocyte count, clinical variables and the pneumonia severity index
      (PSI) were measured. ProADM levels were measured with a new sandwich immunoassay
      for mid regional ProADM (MR-proADM, Brahms AG, Hennigsdorf/Berlin, Germany).
      RESULTS: ProADM levels, in contrast to C-reactive protein and leukocyte count,
      increased with increasing severity of CAP, classified according to the PSI score
      (ANOVA, p < 0.001). In patients who died during follow-up, proADM levels on
      admission were significantly higher compared to levels in survivors (2.1 (1.5 to
      3.0) versus 1.0 (0.6 to 1.6) nmol/l, p < 0.001). In a receiver operating
      characteristic (ROC) analysis for survival, the area under the ROC curve (AUC)
      for proADM was 0.76 (95% confidence interval (CI) 0.71-0.81), which was
      significantly higher compared to procalcitonin (p = 0.004), C-reactive protein (p
      < 0.001) and total leukocyte count (p = 0.001) and similar to the AUC of the PSI
      (0.73, p = 0.54). A clinical model including the PSI and proADM increased the
      prognostic accuracy to predict failure compared to a model relying on the PSI
      alone (AUC, 0.77 (0.70 to 0.84), p = 0.03). CONCLUSION: ProADM, as a novel
      biomarker, is a useful tool for the risk stratification of patients with CAP.

PMID- 16805923
TI  - Identification, characterization and comparative genomics of chimpanzee
      endogenous retroviruses.
AB  - BACKGROUND: Retrotransposons, the most abundant and widespread class of
      eukaryotic transposable elements, are believed to play a significant role in
      mutation and disease and to have contributed significantly to the evolution of
      genome structure and function. The recent sequencing of the chimpanzee genome is
      providing an unprecedented opportunity to study the functional significance of
      these elements in two closely related primate species and to better evaluate
      their role in primate evolution. RESULTS: We report here that the chimpanzee
      genome contains at least 42 separate families of endogenous retroviruses, nine of
      which were not previously identified. All but two (CERV 1/PTERV1 and CERV 2) of
      the 42 families of chimpanzee endogenous retroviruses were found to have
      orthologs in humans. Molecular analysis (PCR and Southern hybridization) of CERV
      2 elements demonstrates that this family is present in chimpanzee, bonobo,
      gorilla and old-world monkeys but absent in human, orangutan and new-world
      monkeys. A survey of endogenous retroviral positional variation between
      chimpanzees and humans determined that approximately 7% of all chimpanzee-human
      INDEL variation is associated with endogenous retroviral sequences. CONCLUSION:
      Nine families of chimpanzee endogenous retroviruses have been transpositionally
      active since chimpanzees and humans diverged from a common ancestor. Seven of
      these transpositionally active families have orthologs in humans, one of which
      has also been transpositionally active in humans since the human-chimpanzee
      divergence about six million years ago. Comparative analyses of orthologous
      regions of the human and chimpanzee genomes have revealed that a significant
      portion of INDEL variation between chimpanzees and humans is attributable to
      endogenous retroviruses and may be of evolutionary significance.

PMID- 16805924
TI  - General and disease-specific risk factors for depression after ischemic stroke: a
      two-step Cox regression analysis.
AB  - BACKGROUND: Post-stroke depression (PSD) frequently complicates stroke and is
      associated with an impaired functional outcome, more severe cognitive deficits, a
      reduced quality of life, and a higher mortality. The aim of this study was to
      assess whether general risk factors for major depressive disorder (MDD) in the
      community are also risk factors for PSD, and to identify additional, stroke
      related risk factors. METHODS: In a hospital setting, 190 consecutively admitted
      patients were assessed for MDD 1 month after stroke, and at follow-up after 3, 6,
      9 and 12 months. A Cox model was created with four established risk factors for
      MDD in the community (female sex, prior personal history of depression, positive
      family history of depression, and somatic comorbidity other than stroke). Five
      potential disease-related risk factors (disability, cognitive deterioration,
      inter- and intrahemispheric lesion location, and generalized vascular damage on
      computed tomography (CT) scan) were then added individually to this model, to see
      whether these would improve the significance of the overall model. RESULTS: The
      Cox model of four general risk factors for depression in the community was shown
      to be a valid model to predict depression in stroke patients. Of the disease
      specific factors, only incorporation of "disability" in this model improved its
      significance. CONCLUSION: Established risk factors for depression in the
      community are also predictors of depression in the first year after stroke.
      Disability is a non-specific disease-related variable that is associated with
      PSD. The contribution of stroke-specific factors may be less than is generally
      assumed.

PMID- 16805925
TI  - Development and validation of the Geriatric Anxiety Inventory.
AB  - BACKGROUND: Anxiety symptoms and anxiety disorders are highly prevalent among
      elderly people, although infrequently the subject of systematic research in this
      age group. One important limitation is the lack of a widely accepted instrument
      to measure dimensional anxiety in both normal old people and old people with
      mental health problems seen in various settings. Accordingly, we developed and
      tested of a short scale to measure anxiety in older people. METHODS: We generated
      a large number of potential items de novo and by reference to existing anxiety
      scales, and then reduced the number of items to 60 through consultation with a
      reference group consisting of psychologists, psychiatrists and normal elderly
      people. We then tested the psychometric properties of these 60 items in 452
      normal old people and 46 patients attending a psychogeriatric service. We were
      able to reduce the number of items to 20. We chose a 1-week perspective and a
      dichotomous response scale. RESULTS: Cronbach's alpha for the 20-item Geriatric
      Anxiety Inventory (GAI) was 0.91 among normal elderly people and 0.93 in the
      psychogeriatric sample. Concurrent validity with a variety of other measures was
      demonstrated in both the normal sample and the psychogeriatric sample. Inter
      rater and test-retest reliability were found to be excellent. Receiver operating
      characteristic analysis indicated a cut-point of 10/11 for the detection of DSM
      IV Generalized Anxiety Disorder (GAD) in the psychogeriatric sample, with 83% of
      patients correctly classified with a specificity of 84% and a sensitivity of 75%.
      CONCLUSIONS: The GAI is a new 20-item self-report or nurse-administered scale
      that measures dimensional anxiety in elderly people. It has sound psychometric
      properties. Initial clinical testing indicates that it is able to discriminate
      between those with and without any anxiety disorder and between those with and
      without DSM-IV GAD.

PMID- 16805926
TI  - Performance on MMSE sub-items and education level in presenilin-1 mutation
      carriers without dementia.
AB  - BACKGROUND: Spanish-language screening tests that are sensitive to the early
      cognitive changes of Alzheimer's disease (AD) are needed. Persons known to be at
      50% risk for young-onset AD due to presenilin-1 (PSEN1) mutations provide the
      opportunity to assess which measures on the Mini-mental State Examination (MMSE)
      are most sensitive to these early changes. METHODS: We performed genetic and
      Spanish-language cognitive testing on 50 Mexican persons without dementia at risk
      for inheriting PSEN1 mutations. We then compared the performance on sub-items of
      the MMSE between PSEN1 mutation carriers (MCs) and non-carriers (NCs) using t
      tests and Fisher's exact tests. Exploratory multiple logistic regression analyses
      were also performed. RESULTS: Twenty-nine persons were MCs and 21 NCs. NCs tended
      to achieve higher levels of education (p = 0.039) than did MCs. MCs tended to
      perform more poorly when spelling "MUNDO" backwards and on Orientation,
      particularly regarding the date. In multiple regression analyses the ability of
      backwards spelling to predict PSEN1 mutation status was reduced when education
      was included as an independent variable. CONCLUSION: Subjects in the earliest
      stage of PSEN1-related AD showed deficits on orientation to date and in divided
      attention when spelling backwards. It is unclear if educational level should be
      considered an associated feature or a con-founding variable in this population
      although it should be taken into account when considering performance on the MMSE
      task of divided attention. The relative lack of deficits on delayed recall of
      three words probably represents the insensitivity of this measure in early AD.
      This study supports the utility of autosomal dominant AD as a model of the more
      common sporadic form of the disorder.

PMID- 16805927
TI  - Remembering to age successfully: evaluation of a successful aging approach to
      memory enhancement.
AB  - BACKGROUND: Memory enhancement programs that can significantly improve actual
      memory performance and subjective perceptions of everyday memory in elderly
      people are rare. This study was designed to evaluate a new memory enhancement
      program incorporating principles of successful aging, designed to enhance
      subjective and objective everyday memory in community-dwelling old people.
      METHODS: Two matched groups of 20 healthy community-dwelling elderly adults were
      assessed on measures of objective and subjective memory performance before and
      after participating in a memory enhancement or active control condition. RESULTS:
      Planned multivariate analysis of variance (MANOVA) on change scores showed that
      participants in the memory enhancement program improved significantly on both
      objective and subjective measures. Specifically, greater improvement was
      demonstrated on a verbal paired associates task, story recall, face recognition,
      contentment with memory, and use of memory strategies. CONCLUSIONS: Although a
      fully randomized design was not used, the results are promising, suggesting that
      memory training incorporating principles of successful aging can enhance memory
      performance in healthy old people, objectively and subjectively.

PMID- 16805928
TI  - Keep music live: music and the alleviation of apathy in dementia subjects.
AB  - BACKGROUND: A recent Cochrane report concluded that more and better quality
      research is required to investigate the effectiveness of music therapy in
      reducing problems in behavioral, social, emotional and cognitive domains in
      patients with dementia. This randomized placebo-controlled trial with blinded
      observer rater aimed to explore whether music, live or pre-recorded, is effective
      in the treatment of apathy in subjects with moderate to severe dementia. METHODS:
      Thirty-two subjects meeting ICD-10 diagnostic criteria for moderate to severe
      dementia and fulfilling diagnostic criteria for apathy were exposed to live
      interactive music, passive pre-recorded music or silence for 30 minutes. Each
      subject was randomized to 30-minute music or silent periods and was video
      recorded and the muted recording analyzed every 3 minutes using dementia care
      mapping to assess the quality of engagement to the blinded music intervention.
      RESULTS: Compared to low baseline levels of positive engagement (12.5%) in the
      silent placebo period, the majority of subjects (69%), regardless of dementia
      severity, showed a significant and positive engagement to live music. Engagement
      to pre-recorded music was non-significant, with just 25% of all subjects showing
      positive engagement. No subjects showed any evidence of experiencing a state of
      ill-being during either the live or pre-recorded music sessions. CONCLUSIONS:
      During the intervention, live interactive music has immediate and positive
      engagement effects in dementia subjects with apathy, regardless of the severity
      of their dementia. Pre-recorded music is non-harmful but less clearly beneficial.

PMID- 16805929
TI  - Event-related fMRI of word classification and successful word recognition in
      subjects at genetically enhanced risk of schizophrenia.
AB  - BACKGROUND: Verbal declarative memory is a core deficit in schizophrenia
      patients, seen to a lesser extent in unaffected biological relatives.
      Neuroimaging studies suggest volumetric differences and aberrant function in
      prefrontal and temporal regions in schizophrenia patients compared to controls.
      These deficits are also reflected in the small number of similar investigations
      in unaffected biological relatives. However, it is unclear the extent to which
      dysfunction is genetically mediated or a feature of the established illness.
      METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic
      resonance imaging (fMRI) was used to measure brain activation in 68 biological
      relatives of schizophrenia patients (of whom 27 experienced transient or isolated
      psychotic symptoms) and 21 controls during verbal classification and recognition.
      RESULTS: During word classification, the high-risk group showed a greater
      response relative to controls in the right inferior frontal gyrus. During correct
      recognition (relative to correct rejection), the high-risk group showed
      significantly greater response relative to controls in the right cerebellum. When
      the high-risk group was split into those with (HR+) and without (HR-) psychotic
      symptoms, the increased response in the right inferior frontal gyrus was only
      seen when the HR+ were compared to controls. The greater cerebellar response was
      seen when both HR groups were compared to controls. CONCLUSIONS: Activation
      increases in the right inferior frontal gyrus and cerebellum in high-risk
      subjects compared to controls during a relatively low-load memory task are likely
      to represent compensation for genetically mediated abnormalities. This is
      consistent with a leftward shift of the inverted 'U' load-response model of
      cognitive function in schizophrenia.

PMID- 16805930
TI  - Sensory blockade after thoracic paravertebral injection of ropivacaine or
      bupivacaine.
AB  - BACKGROUND AND OBJECTIVE: No clinical trials comparing the characteristics of
      sensory blockade caused by various local anaesthetics in thoracic paravertebral
      blockade have been published. The aim of this prospective study was a clinical
      assessment of sensory blockade after paravertebral injection of ropivacaine or
      bupivacaine in patients undergoing modified radical mastectomy. METHODS: Seventy
      ASA I-II patients were randomized to receive a single injection of ropivacaine
      0.5% (n = 35) or bupivacaine 0.5% (n = 35) at the T4 level. General anaesthesia
      with propofol and fentanyl was provided during the procedure and patients were
      not intubated. The following parameters were analysed: duration and dynamics of
      the sensory blockade and the patient's and surgeon's assessment. RESULTS: Both
      ropivacaine and bupivacaine provided a similar level of analgesia. Ropivacaine
      was characterized by more rapid onset - after only 5 min 53% of patients in this
      group had the extent of sensory blockade wide enough to perform modified radical
      mastectomy in comparison to only 20% after bupivacaine (P 9 segments blocked) was
      noted more often in the ropivacaine group (88% vs. 65%, P < 0.05), lasted longer
      and appeared to be wider than sensory blockade produced by bupivacaine.
      Regression of sensory blockade was initially similar, but after 24 h sensory
      blockade in the ropivacaine group still had a potential to provide analgesia for
      modified radical mastectomy in 81% of patients in comparison to only 50% of such
      patients in the bupivacaine group (P < 0.05). Degree of postoperative pain,
      performance of the cardiovascular system, consumption of medications and
      complications were all similar between the study groups. CONCLUSIONS: Both agents
      provide satisfactory conditions for mastectomy, but ropivacaine seems to be
      superior to bupivacaine for thoracic paravertebral blockade during breast cancer
      surgery.

PMID- 16805931
TI  - The effect of fentanyl and remifentanil, with or without ketoprofen, on pain
      after thyroid surgery: a randomized-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: This study was designed to quantify the additional
      postoperative analgesic efficacy of a single dose of ketoprofen in patients
      undergoing thyroid surgery using two different intraoperative analgesic regimens.
      METHODS: One hundred and twenty patients were randomly assigned to one of four
      groups: intraoperative fentanyl or remifentanil with or without ketoprofen (n =
      30 for each group). Intravenous ketoprofen (1.5 mg kg-1) or saline was
      administered 45 min before the end of surgery. Pain scores, opioid demand and
      length of stay in the postanaesthesia care unit were assessed in a blinded
      manner. RESULTS: Patients receiving intraoperative fentanyl with saline had
      significantly lower visual analogue scale pain scores in the postanaesthesia care
      unit compared with those receiving intraoperative remifentanil with saline (55 +/
      10 mm vs. 80 +/- 18 mm, P < 0.05) and they stayed shorter in the postanaesthesia
      care unit (86 +/- 24 min vs. 126 +/- 37 min). In conjunction with intraoperative
      fentanyl, ketoprofen significantly decreased postoperative pain scores (40 +/- 10
      mm, P < 0.05 compared with fentanyl alone) and opioid demand (4 of 30 patients
      vs. 14 of 30 patients compared with fentanyl alone, P < 0.05). Patients receiving
      intraoperative remifentanil had no additional analgesic benefit with ketoprofen.
      CONCLUSION: After thyroid surgery, patients receiving intraoperative fentanyl had
      lower pain scores and needed less rescue analgesia compared with patients
      receiving intraoperative remifentanil. The adjunction of ketoprofen further
      improved analgesia in patients who received intraoperative fentanyl only.

PMID- 16805932
TI  - Ondansetron or droperidol for prophylaxis of nausea and vomiting after
      intrathecal morphine.
AB  - BACKGROUND AND OBJECTIVE: There is a controversy regarding the best drug for
      prevention of nausea and vomiting in patients receiving intrathecal morphine. The
      aim of this study was to examine efficacy and tolerability of droperidol compared
      with ondansetron for the prevention of morphine-induced nausea and vomiting.
      METHODS: In a randomized, placebo-controlled trial, 120 women undergoing
      Caesarean section under spinal anaesthesia with intrathecal morphine 0.1 mg
      received intravenous ondansetron 4 mg (n = 40), droperidol 1.25 mg (n = 40) or
      saline (n = 40) immediately after umbilical-cord clamping. Nausea and vomiting
      were graded according to intensity at 1, 2, 4, 6, 12 and 24 h. RESULTS: Nausea or
      vomiting occurred in 14 patients (35%) in the placebo group, 4 (10%) in the
      ondansetron group and 10 (25%) in the droperidol group; the difference between
      ondansetron and placebo was statistically significant (P = 0.007). Eleven of the
      14 placebo patients (27.5%) vomited, compared with none of the 4 ondansetron
      patients (vs. placebo, P = 0.0004) and 5 of the droperidol patients (vs. placebo,
      P = 0.18). Three of the 14 placebo patients (7.5%) were nauseous, compared with 4
      (10%) receiving ondansetron and 5 (12.5%) receiving droperidol. CONCLUSIONS:
      Ondansetron was effective in reducing the incidence of nausea and vomiting in
      patients receiving intrathecal morphine for Caesarean section.

PMID- 16805933
TI  - A new simple tool for tonometric determination of the PCO2 in the
      gastrointestinal tract: in vitro and in vivo validation studies.
AB  - BACKGROUND AND OBJECTIVE: Following the discovery of the feasibility of assessing
      the adequacy of the splanchnic perfusion by means of gastrotonometry, this
      technique became extensively used in clinical practice and in research. At
      present, high-technology instruments are available for the purpose. However,
      there is still a need for a simple, cheap tool that is easily applicable for
      patients of all ages. The present article describes such a tool and presents the
      results of in vitro and in vivo validation measurements with it. METHODS: Balloon
      free tonometric probes consisting of silicone rubber tubes were developed. In
      vitro measurements of the uptake of CO2 inside the probes and for comparison in a
      conventional ballooned intestinal tonometer were made in a closed container
      maintained at 37 degrees C. In in vivo studies in anaesthetized dogs, the
      tonometric PCO2 values were determined with a tonometric probe and catheter
      introduced simultaneously into the ileum of the animals and the results were
      analysed by the Bland-Altman method. RESULTS: The in vitro equilibration studies
      revealed that the filling media inside the probes equilibrated rapidly with the
      PCO2 content of the chamber. The data obtained from the in vivo investigations
      with the two different methods demonstrated a statistically significant linear
      association (correlation coefficient: 0.778, significance: P < 0.001).
      CONCLUSION: The new simple tonometric probe described appears to be a reliable
      tool with certain advantages for gastric tonometry. However, further studies are
      warranted before its general clinical use.

PMID- 16805934
TI  - Gabapentin reduces cardiovascular responses to laryngoscopy and tracheal
      intubation.
AB  - BACKGROUND AND OBJECTIVE: We have compared the effects of gabapentin on arterial
      pressure and heart rate at induction of anaesthesia and tracheal intubation in a
      randomized double-blind study. METHODS: Ninety normotensive patients (ASA I)
      undergoing elective surgery were divided into three groups of 30 patients each.
      Patients received oral placebo (Group I), 400 mg of gabapentin (Group II) or 800
      mg of gabapentin (Group III) 1 h prior to surgery in the operating theatre. After
      induction of anaesthesia heart rate and mean arterial pressure were recorded at
      baseline 1, 3, 5, 10 and 15 min after intubation. RESULTS: Patients receiving
      placebo and 400 mg gabapentin showed a significant increase in blood pressure and
      heart rate associated with tracheal intubation compared to baseline levels and
      Group III. There was significant decrease in heart rate and arterial pressure in
      Group III after intubation 1, 3, 5 and 10 min (P < 0.001, P < 0.001, P < 0.05 and
      P < 0.05, respectively) compared to Groups I and II. CONCLUSION: Given 1 h before
      operation gabapentin 800 mg blunted the arterial pressure and heart rate increase
      in first 10 min due to endotracheal intubation. Oral administration of gabapentin
      800 mg before induction of anaesthesia is a simple and practical method for
      attenuating pressor response to laryngoscopy and tracheal intubation after
      standard elective induction.

PMID- 16805935
TI  - Model-based control of neuromuscular block using mivacurium: design and clinical
      verification.
AB  - BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent
      dosing adjustments for individual patient's needs. In this study, we verified a
      new closed-loop controller for mivacurium dosing in clinical trials. METHODS:
      Fifteen patients were studied. T1% measured with electromyography was used as
      input signal for the model-based controller. After induction of propofol/opiate
      anaesthesia, stabilization of baseline electromyography signal was awaited and a
      bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal
      intubation. Closed-loop infusion was started thereafter, targeting a
      neuromuscular block of 90%. Setpoint deviation, the number of manual
      interventions and surgeon's complaints were recorded. Drug use and its
      variability between and within patients were evaluated. RESULTS: Median time of
      closed-loop control for the 11 patients included in the data processing was 135
      [89-336] min (median [range]). Four patients had to be excluded because of sensor
      problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither
      manual interventions nor complaints from the surgeons were recorded. Mean
      necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1.
      Intrapatient variability of mean infusion rates over 30-min interval showed high
      differences up to a factor of 1.8 between highest and lowest requirement in the
      same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with
      mivacurium using our model-based controller. The amount of mivacurium needed to
      maintain T1% at defined constant levels differed largely between and within
      patients. Closed-loop control seems therefore advantageous to automatically
      maintain neuromuscular block at constant levels.

PMID- 16805936
TI  - A comparison of the effect on gastric emptying of propofol or dexmedetomidine in
      critically ill patients: preliminary study.
AB  - BACKGROUND: Propofol and dexmedetomidine are widely used for sedation in the
      intensive care unit yet there are limited data on its effects on gastric
      motility. In our preliminary study, we examined whether or not any effect of
      propofol and dexmedetomidine on gastric emptying is preserved in critically ill
      patients. METHODS: Twenty-four critically ill, enterally fed adult patients each
      received enteral feeding via a nasogastric tube at 50 mL h-1 throughout the 5-h
      study period. Either propofol 2 mg kg-1 h-1 (n = 12, Group P) or dexmedetomidine
      0.2 microg kg-1 h- (n = 12, Group D) was given intravenously over 5 h. Gastric
      motility was measured indirectly by analysis of the absorption over time of 1.5 g
      of paracetamol administered into the stomach at the start of the study period. At
      the beginning and end of the study, residual gastric volume and pH of residual
      gastric fluid were measured. RESULTS: Gastric residual volume measured at the end
      of propofol infusion (19.33 +/- 11.33) was found to be higher when compared with
      the volume measured before infusion (11.33 +/- 4.84) and after dexmedetomidine
      infusion (9.17 +/- 4.54). But, there was no difference between groups in gastric
      emptying time (AUC120 894.53 +/- 499.39 vs. 1113.46 +/- 598.09 propofol and
      dexmedetomidine groups, respectively). CONCLUSION: In our study, gastric residual
      volume measured at the end of propofol infusion was found to be higher when
      compared with the volume measured before infusion and after dexmedetomidine
      infusion. There was no difference between groups in gastric emptying time.

PMID- 16805937
TI  - Intensive insulin therapy to non-cardiac ICU patients: a prospective study.
AB  - OBJECTIVE: Intensive insulin therapy reduced mortality in patients admitted to an
      intensive care unit following mainly cardiac surgery. The aim of this prospective
      study was to evaluate, if intensive insulin therapy could reduce mortality in
      medical and non-cardiac surgical patients admitted to a multidisciplinary
      intensive care unit. PATIENTS AND METHODS: For 6 months all adult patients,
      admitted to the intensive care unit, were included. Insulin was administered, if
      blood glucose 12 mmol L-1. For the next 6 months blood glucose level was reduced
      with intensive insulin therapy (aim 4.4 < BG < 6.1 mmol L-1); 271 patients were
      included. Patient characteristics data, APACHE II score, morbidity and mortality
      were recorded. RESULTS: At admission the two groups were comparable. The overall
      relative mortality was reduced 20% in the intensive insulin treated group (n.s.).
      In the intensive insulin treated group mortality was 13.1% in the medical
      patients and 11.2% in the surgical patients compared to 15.8% and 14.4%,
      respectively, in the conventional treated group (n.s.). The frequency of
      secondary infections was 21.5% in the intensive insulin treated group and 16.0%
      in the conventional treated group (n.s.). The proportion of hypoglycaemia
      increased from 4% to 14% (P < 0.05). CONCLUSIONS: Following intensive insulin
      therapy there was a trend towards reduced mortality in medical and non-cardiac
      surgical patients but less pronounced as in cardiac surgical patients. Intensive
      insulin therapy increased the frequency of hypoglycaemia. Around 4400 patients
      would have to be included in any future randomized study to reach significance.

PMID- 16805938
TI  - Comparing different methods of cardiac output determination: a call for
      consensus.

PMID- 16805940
TI  - An unusual case of airway obstruction.

PMID- 16805941
TI  - Tracheal intubation without muscle relaxants: large doses of opioids, small
      endotracheal tubes.

PMID- 16805943
TI  - Correct sizing of the CobraPLA is necessary for valid study results.

PMID- 16805944
TI  - Fascia-iliaca compartment block for femoral bone fracture in prehospital medicine
      in a 6-yr-old child.

PMID- 16805945
TI  - Morphine and methylprednisolone after knee surgery.

PMID- 16805946
TI  - Role of CYP pharmacogenetics and drug-drug interactions in the efficacy and
      safety of atypical and other antipsychotic agents.
AB  - Cytochrome P450 (CYP) drug oxidases play a pivotal role in the elimination of
      antipsychotic agents, and therefore influence the toxicity and efficacy of these
      drugs. Factors that affect CYP function and expression have a major impact on
      treatment outcomes with antipsychotic agents. In particular, aspects of CYP
      pharmacogenetics, and the processes of CYP induction and inhibition all influence
      in-vivo rates of drug elimination. Certain CYPs that mediate the oxidation of
      antipsychotic drugs exhibit genetic variants that may influence in-vivo activity.
      Thus, single nucleotide polymorphisms (SNPs) in CYP genes have been shown to
      encode enzymes that have decreased drug oxidation capacity. Additionally,
      psychopharmacotherapy has the potential for drug-drug inhibitory interactions
      involving CYPs, as well as drug-mediated CYP induction. Literature evidence
      supports a role for CYP1A2 in the clearance of the atypical antipsychotics
      clozapine and olanzapine; CYP1A2 is inducible by certain drugs and environmental
      chemicals. Recent studies have suggested that specific CYP1A2 variants possessing
      individual SNPs, and possibly also SNP combinations (haplotypes), in the 5'
      regulatory regions may respond differently to inducing chemicals. CYP2D6 is an
      important catalyst of the oxidation of chlorpromazine, thioridazine, risperidone
      and haloperidol. Certain CYP2D6 allelic variants that encode enzymes with
      decreased drug oxidation capacity are more common in particular ethnic groups,
      which may lead to adverse effects with standard doses of psychoactive drugs.
      Thus, genotyping may be useful for dose optimization with certain psychoactive
      drugs that are substrates for CYP2D6. However, genotyping for inducible CYPs is
      unlikely to be sufficient to direct therapy with all antipsychotic agents. In
      vivo CYP phenotyping with cocktails of drug substrates may assist at the
      commencement of therapy, but this approach could be complicated by
      pharmacokinetic interactions if applied when an antipsychotic drug regimen is
      ongoing.

PMID- 16805947
TI  - Formulations generated from ethanol-based proliposomes for delivery via medical
      nebulizers.
AB  - Multilamellar and oligolamellar liposomes were produced from ethanol-based soya
      phosphatidyl-choline proliposome formulations by addition of isotonic sodium
      chloride or sucrose solutions. The resultant liposomes entrapped up to 62% of
      available salbutamol sulfate compared with only 1.23% entrapped by conventionally
      prepared liposomes. Formulations were aerosolized using an air-jet nebulizer
      (Pari LC Plus) or a vibrating-mesh nebulizer (Aeroneb Pro small mesh, Aeroneb Pro
      large mesh, or Omron NE U22). All vibrating-mesh nebulizers produced aerosol
      droplets having larger volume median diameter (VMD) and narrower size
      distribution than the air-jet nebulizer. The choice of liposome dispersion medium
      had little effect on the performance of the Pari nebulizer. However, for the
      Aeroneb Pro small mesh and Omron NE U22, the use of sucrose solution tended to
      increase droplet VMD, and reduce aerosol mass and phospholipid outputs from the
      nebulizers. For the Aeroneb Pro large mesh, sucrose solution increased the VMD of
      nebulized droplets, increased phospholipid output and produced no effect on
      aerosol mass output. The Omron NE U22 nebulizer produced the highest mass output
      (approx. 100%) regardless of formulation, and the delivery rates were much higher
      for the NaCl-dispersed liposomes compared with sucrose-dispersed formulation.
      Nebulization produced considerable loss of entrapped drug from liposomes and this
      was accompanied by vesicle size reduction. Drug loss tended to be less for the
      vibrating-mesh nebulizers than the jet nebulizer. The large aperture size mesh (8
      mum) Aeroneb Pro nebulizer increased the proportion of entrapped drug delivered
      to the lower stage of a twin impinger. This study has demonstrated that liposomes
      generated from proliposome formulations can be aerosolized in small droplets
      using air-jet or vibrating-mesh nebulizers. In contrast to the jet nebulizer, the
      performance of the vibrating-mesh nebulizers was greatly dependent on
      formulation. The high phospholipid output produced by the nebulizers employed
      suggests that both air-jet and vibrating-mesh nebulization may provide the
      potential of delivering liposome-entrapped or solubilized hydrophobic drugs to
      the airways.

PMID- 16805948
TI  - Incorporation of proteins within alginate fibre-based scaffolds using a post
      fabrication entrapment method.
AB  - In this study, a physical entrapment process was explored for the incorporation
      of proteins within preformed fibrous alginates and the release profile was tuned
      by varying the processing parameters. The entrapment process was carried out in a
      series of aqueous solutions at room temperature and involved pre-swelling of the
      fibrous alginate within a Na(+)-rich solution, followed by exposure to the
      protein of choice and entrapping it by re-establishing cross-links of alginate
      with BaCl2. Entrapment and release of fluorescein isothiocyanate-labelled bovine
      serum albumin (FITC-BSA), a model protein, was studied. It was found that a
      sustained release of the incorporated protein in cell culture medium for about 6
      days was achieved. The main factors determining the release profile included the
      NaCl/CaCl2 ratio in the pre-swelling solution, protein concentration, and the
      exposure time. To retard protein release, alginate fibres with entrapped FITC-BSA
      were processed together with poly(D, L-lactide) (PDLLA) into porous alginate
      fibre/PDLLA composites using supercritical CO2. In this manner, release of the
      protein for up to 3 months was achieved.

PMID- 16805949
TI  - In-vitro transcutaneous delivery of ketoprofen and polyunsaturated fatty acids
      from a pluronic lecithin organogel vehicle containing fish oil.
AB  - This work explored the use of pluronic lecithin organogel (PLO) as a base for the
      delivery of bioactive polyunsaturated fatty acids from fish oil, eicosapentaenoic
      acid (EPA), docosahexaenoic acid (DHA) and ketoprofen. PLO was adapted to contain
      fish oil, ketoprofen, or both, and 1,8-cineole as penetration enhancer, and used
      to determine the in-vitro permeation from infinite and finite dosing protocols
      across full thickness porcine skin. Oruvail gel (2.5% ketoprofen) was included
      for comparison. No EPA or DHA was found to permeate skin when applied as an
      infinite dose. From multiple finite doses, small amount (max. 0.22%) of fish oil
      were found to permeate the skin. This indicates retention of fish oil within the
      gel matrix and that the viable domain of full thickness skin was a significant
      barrier. Greater amounts of EPA and DHA were delivered in the presence of
      ketoprofen indicating co-transport resulting from selective complexation,
      although no enhancement was observed using 1,8-cineole. Unlike EPA and DHA,
      substantial amounts of ketoprofen permeated when applied as infinite doses.
      Oruvail, a Carbopol 940-based hydrogel containing 2.5% ketoprofen and ethanol,
      delivered the greatest amount, although similar to the PLO gel containing 5%
      ketoprofen. The addition of propylene glycol enhanced permeation, although the
      presence of fish oil in the PLO gel inhibited ketoprofen permeation. When applied
      as multiple finite doses a maximum of 76 microm cm(-2) (1.12%) was delivered,
      which was reduced by the presence of 1,8-cineole. Greater permeation was again
      observed with Oruvail by a factor of two and with half the ketoprofen dose. To
      conclude, a PLO-based gel is capable of delivering EPA and DHA via a repeat
      finite dosing regimen, although there is evidence for the retention of these very
      lipophilic molecules within the gel matrix. Although to a lesser extent than EPA
      and DHA, ketoprofen was also substantially retained, as exemplified by the
      superior delivery rates from Oruvail. Finally, this work has highlighted the
      importance of using an appropriate topical dosing method to match the intended
      use of a product.

PMID- 16805950
TI  - Transepithelial transport of morphine and mannitol in Caco-2 cells: the influence
      of chitosans of different molecular weights and degrees of acetylation.
AB  - The object of this study was to compare the effect of chitosans of different
      number-average molecular weights (MWs) and degrees of acetylation (F(A)) on
      transepithelial transport of morphine in Caco-2 cells. Caco-2 monolayers on
      polycarbonate (PC) membranes (0.5 cm(2)) were incubated with morphine (10 microM)
      or mannitol (55 microM) for 180 min. Samples for analysis of morphine (LCMSMS)
      and mannitol (liquid scintillation) were drawn at 45, 90, 120 and 180 min.
      Transepithelial electrical resistance (TEER) and transmission electron microscopy
      were used to monitor cell integrity. In controls, morphine transport was half
      that of mannitol. Chitosans affected the transport of morphine and mannitol
      similarly. For chitosans with similar F(A) (0.32-0.43) and varying MWs (7-200
      kD), transport was increased at MWs of 29 kD or more. Among chitosans of similar
      MWs (180-300 kD) and varying F(A) (0.01-0.61), those with the highest F(A) (0.61)
      had the least effect, while chitosans with F(A)/MW 0.01/250 and 0.17/300 promoted
      the greatest transport. An F(A)/MW of 0.32/200 and 0.43/170 induced a high and
      stable transport rate. Chitosans may enhance transepithelial transport of
      morphine by the same mechanism as for mannitol. Chitosans with F(A) of 0.3-0.4
      and MW of approx. 200 kD seem favourable in this respect.

PMID- 16805951
TI  - A comparison of intestinal lymphatic transport and systemic bioavailability of
      saquinavir from three lipid-based formulations in the anaesthetised rat model.
AB  - Saquinavir is a lipophilic, poorly water-soluble HIV protease inhibitor that
      undergoes extensive first-pass metabolism and exhibits poor oral bioavailability.
      Redirection of the absorption pathway of anti-HIV compounds from the portal blood
      to the HIV-rich intestinal lymphatics may enhance therapeutic efficacy and reduce
      the extent of the first-pass effect. This study investigates the potential of
      targeted intestinal lymphatic transport of saquinavir via a lipid formulation
      approach. Three formulations containing oleic acid were examined: cremophor-oleic
      acid mixed micelles, D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS)
      oleic acid mixed micelles and an oleic acid microemulsion. The mesenteric lymph
      duct cannulated anaesthetised rat model was employed. Plasma and lymph samples
      were analysed by HPLC. Lymph triglyceride was measured using an enzymatic
      colorimetric technique. The extent of lymphatic transport from the lipid vehicles
      was 0.025-0.05% of the dose administered. The microemulsion produced higher and
      more prolonged mesenteric lymph concentrations than the micellar formulations. A
      strong correlation existed between the concentration of saquinavir in intestinal
      lymph and lymph triglyceride levels. The systemic bioavailability was estimated
      to be 8.5% and 4.8% for the cremophor mixed micelle and the microemulsion,
      respectively. The cremophor mixed micelles produced higher bioavailability than
      TPGS mixed micelles, implying that the nature of the surfactant can influence the
      distribution of drug between lymph and plasma.

PMID- 16805952
TI  - Enhanced cellular uptake of Ara-C via a peptidomimetic prodrug, L-valyl-ara-C in
      Caco-2 cells.
AB  - This study aimed to investigate the gastrointestinal stability and the cellular
      uptake characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C
      (cytarabine). After the synthesis of L-valyl-ara-C via the incorporation of L
      valine into the N4-amino group of the cytosine ring in araC, the gastrointestinal
      stability of L-valyl-ara-C was examined using artificial gastric juice and
      artificial intestinal fluids. The cellular uptake characteristics of L-valyl-ara
      C were also examined in Caco-2 cells. The disappearance half-life of L-valyl-ara
      C was 2.2 h in artificial gastric juice, while the degradation of L-valyl-ara-C
      was negligible in artificial intestinal fluid and also in the supernatant above
      the Caco-2 cell monolayer during the 2-h incubation. The cellular accumulation of
      L-valyl-ara-C was 5-fold higher than that of ara-C in Caco-2 cells. Furthermore,
      the cellular uptake of L-valyl-ara-C did not increase proportionally to the
      increase in drug concentration. The cellular accumulation of L-valyl-ara-C was
      significantly reduced in the presence of uridine, p-aminohippurate,
      tetraethylammonium and small dipeptides, while it was not changed in the presence
      of L-valine and benzoic acid, suggesting that L-valyl-ara-C could interact with
      multiple uptake transporters, including peptide transporters, organic anion and
      cation transporters and nucleoside transporters, but might not interact with
      amino acid transporters. In conclusion, L-valyl-ara-C could be effective to
      improve the oral absorption of ara-C via the carrier-mediated transport pathway.

PMID- 16805953
TI  - Antiproliferative effect of salvianolic acid A on rat hepatic stellate cells.
AB  - Suppression of activation or proliferation, or induction of apoptosis in hepatic
      stellate cells (HSCs) have been proposed as therapeutic strategies against liver
      fibrosis. Salvia miltiorrhiza has been reported to exert antifibrotic effects in
      rats with hepatic fibrosis, but its mechanisms of action remain to be clarified.
      We have investigated the effects of salvianolic acid A (Sal A), an active
      principle from S. miltiorrhiza, on the proliferation-related biomarkers in a cell
      line of rat HSCs (HSC-T6) stimulated with platelet-derived growth factor-BB
      homodimer (PDGF-BB). DNA synthesis (bromodeoxyuridine (BrdU) incorporation), cell
      cycle related proteins and apoptosis markers were determined to evaluate the
      inhibitory effects of Sal A. The results showed that Sal A (1-10 microM)
      concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU
      incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF
      BB-incubated HSCs, together with a reduction of Bcl-2 protein expression,
      induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of
      cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor
      phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct
      cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental
      concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC
      proliferation, partially through apoptosis induction.

PMID- 16805954
TI  - The relationship between structure and antioxidative activity of piperidine
      nitroxides.
AB  - We have investigated the relationship between structure and antioxidative
      activity of piperidine nitroxides which were substituted by different groups at
      the 4-position. All of the tested piperidine nitroxides inhibited malondialdehyde
      (MDA) generation caused either spontaneously or by a hydroxyl free radical
      generation system (Fe2+-ascorbic acid) in homogenates of liver, heart and kidney
      of rats, and antagonized H2O2-induced haemolysis from rat erythrocytes in a
      concentration-dependent manner. The same rank was followed: Bis-(4-amino-2,2,6,6
      tetramethyl piperidinooxyl) (4-BIS-Tempo) and 4-azido-2,2,6,6-tetramethyl
      piperidinooxyl (4-N(3)-Tempo) > 4-isothiocyanate-2,2,6,6-tetramethyl
      piperidinooxyl (4-ISO-Tempo), 4-2', 4'-dinitrophenylhy-drazone-2,2,6,6
      tetramethyl piperidinooxyl (4-D-Tempo), 4-sulfonate-2,2,6,6-tetramethyl
      piperidinooxyl (4-S-Tempo) and 4-amino-2,2,6,6-tetramethyl piperidinooxyl (4
      NH(2)-Tempo) > 4-acetate ester-2,2,6,6-tetramethyl piperidinooxyl (4-A-Tempo) and
      4-benzoate-2,2,6,6-tetramethyl piperidinooxyl (4-B-Tempo). With the exception of
      4-A-Tempo and 4-D-Tempo, the tested piperidine nitroxides inhibited superoxide
      anion (O(2*-)) release from neutrophils stimulated by zymosan. The concentration
      required for inhibiting O(2*-) release was higher than that of inhibiting MDA
      formation and haemolysis. However, 4-amino-2,2,6,6-tetramethyl piperidine (4-NH2
      TempH) and other 4-position substitutes, such as NaN3 and isothiocyanate, had no
      effects on MDA formation, haemolysis or O(2*-) release. The results indicated
      that nitroxides have a wide range of scavenging reactive oxygen species (ROS)
      actions. The nitroxide moiety was the essential group while the 4-position
      substitutes could influence the activity of nitroxides on scavenging ROS.

PMID- 16805955
TI  - Oxidative stress parameters in different systemic rheumatic diseases.
AB  - The involvement of oxidative stress in the pathogenesis of rheumatic disorders,
      such as systemic sclerosis (SSc) and chronic polyarthritides, has been suggested
      yet not thoroughly verified experimentally. We analysed 4 plasmatic parameters of
      oxidative stress in patients with SSc (n = 17), psoriatic arthritis (PsA) (n =
      10) and rheumatoid arthritis (RA) (n = 9) compared with healthy subjects (n =
      22). The biomarkers were: total antioxidant capacity (TAC) measured by ferric
      reducing antioxidant power (FRAP) method, hydroperoxides determined by ferrous
      ion oxidation in presence of xylenol orange (FOX) method and sulfhydryl and
      carbonyl groups assessed by spectrophotometric assays. The results showed
      significantly increased hydroperoxides in SSc, PsA and RA (3.97 +/- 2.25, 4.87 +/
      2.18 and 5.13 +/- 2.36 micromol L(-1), respectively) compared with the control
      group (2.31 +/- 1.40 micromol L(-1); P < 0.05). Sulfhydryls were significantly
      lower in SSc (0.466 +/- 0.081 mmol L(-1)), PsA (0.477 +/- 0.059 mmol L(-1)) and
      RA (0.439 +/- 0.065 mmol L(-1)) compared with the control group (0.547 +/- 0.066
      mmol L(-1); P < 0.05). TAC in all three diseases showed no difference in
      comparison with controls. Carbonyls were significantly higher in RA than in the
      control group (32.1 +/- 42 vs 2.21 +/- 1.0 nmol (mg protein)(-1); P < 0.05). The
      obtained data indicate augmented free radical-mediated injury in these rheumatic
      diseases and suggest a role for the use of antioxidants in prevention and
      treatment of these pathologies.

PMID- 16805956
TI  - A tetravalent RGD ligand for integrin-mediated cell adhesion.
AB  - Monovalent RGD (arginine-glycine-aspartic acid) peptides or polymers furnished
      with RGD in random distributions are employed as cell-scaffolds and gene delivery
      vehicles. However, integrin binding to RGD is dependent on the spatial
      distribution (clustering) of the ligand and intrinsic integrin affinity via
      conformational changes (avidity). Here we have designed and expressed a
      polypeptide consisting of a tetrameric coiled coil and spacer facilitating
      polyvalent (clustered) display of integrin ligands; the RGD motif was used as
      proof of principle. Size-exclusion chromatography and circular dichroism showed
      that the polypeptide self assembled as a tetramer in solution with a defined
      secondary structure. Cell adhesion to surfaces coated with the polypeptide was up
      to 3-fold greater than that for (monovalent) RGDS peptide at equivalent
      concentrations. Moreover, the polypeptide in solution at concentrations >or= 1
      microM inhibited cell adhesion to fibronectin-coated surfaces, while RGDS peptide
      in solution at concentrations up to 500 muM did not. These cell data demonstrate
      that the polypeptide bound integrin receptors in a polyvalent manner. The
      polypeptide will therefore be of use in the engineering of tissue-culture
      scaffolds with increased cell adhesion activity, or to targeted gene delivery
      vehicles, and could incorporate protein ligands in place of the RGD motif.

PMID- 16805957
TI  - Protective effects of Peganum harmala L. extract, harmine and harmaline against
      human low-density lipoprotein oxidation.
AB  - Oxidative modification of low-density lipoprotein (LDL) particles has been
      implicated in the process of atherogenesis. Antioxidants that prevent LDL from
      oxidation may reduce atherosclerosis. We have investigated the protective effect
      of Peganum harmala-extract (P-extract) and the two major alkaloids (harmine and
      harmaline) from the seeds of P. harmala against CuSO4-induced LDL oxidation.
      Through determination of the formation of malondialdehyde (MDA) and conjugated
      diene as well as the lag phase, the extract (P-extract) and compounds were found
      to possess an inhibitory effect. Moreover, harmaline and harmine reduced the rate
      of vitamin E disappearance and exhibited a significant free radical scavenging
      capacity (DPPH*). However, harmaline had a markedly higher antioxidant capacity
      than harmine in scavenging or preventive capacity against free radicals as well
      as inhibiting the aggregation of the LDL protein moiety (apolipoprotein B)
      induced by oxidation. The results suggested that P. harmala compounds could be a
      major source of compounds that inhibit LDL oxidative modification induced by
      copper.

PMID- 16805958
TI  - Apoptosis inducing activity of 4-substituted coumarins from Calophyllum
      brasiliense in human leukaemia HL-60 cells.
AB  - With the objective of identifying anti-tumour-promoting agents, we carried out a
      primary screening of ten 4-substituted coumarins isolated from Calophyllum
      brasiliense Camb. (Guttiferae), to determine the ability of these compounds to
      inhibit proliferation of the human leukaemia cell line HL-60. Among the 4
      substituted coumarins isolated, calophyllolide (2) and mammea B/BB (3) showed
      significant cytotoxicity against HL-60 cells. Fluorescence microscopy with
      Hoechst 33342 staining revealed that the percentage of apoptotic cells with
      fragmented nuclei and condensed chromatin increased in a time-dependent manner
      after treatment with calophyllolide (2) or mammea B/BB (3). In addition, the
      activity of caspase-9 and caspase-3 was also enhanced in a time-dependent manner
      upon treatment with the 4-substituted coumarins 2 and 3. Caspase-9 and caspase-3
      inhibitors suppressed apoptosis induced by 4-substituted coumarins 2 and 3. These
      results suggest that calophyllolide (2) and mammea B/ BB (3) induced apoptosis in
      HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is
      triggered by mitochondrial dysfunction.

PMID- 16805959
TI  - An extract of Lannea microcarpa: composition, activity and evaluation of
      cutaneous irritation in cell cultures and reconstituted human epidermis.
AB  - Lannea microcarpa (Anacardiaceae) is a tropical tree used in African folk
      medicine and commercial dermopharmaceutical formulations. Fractionation and
      analysis of its polar extract allowed the identification of 4'-methoxy-myricetin
      3-O-alpha-L-rhamnopyranoside, myricetin 3-O-alpha-L-rhamnopyranoside, myricetin 3
      O-beta-D-glucopyranoside, vitexin, isovitexin, gallic acid and epi-catechin, as
      the major constituents. In-vivo assay (the croton oil ear test in mice) showed
      that the extract had significant anti-inflammatory effect (ID50 = 900 microg cm(
      2)) but ten times lower than that of indometacin (ID50 = 93 microg cm(-2)), the
      non-steroidal anti-inflammatory drug used as reference. Cytotoxicity and
      cutaneous irritation of the extract and its constituents were investigated. The
      crude extract and its major components did not affect cell viability in-vitro
      either in three different cultures (J774. A1, WEHI-164 and HEK-293) of cells
      grown in monolayers or in the reconstituted human epidermis (RHE, 3D model), nor
      did they cause release of pro-inflammatory mediators (IL-1alpha) or
      histomorphological modification of RHE.

PMID- 16805960
TI  - Relevant activities of extracts and constituents of animals used in traditional
      Chinese medicine for central nervous system effects associated with Alzheimer's
      disease.
AB  - The centipede Scolopendra subspinipes mutilans L. Koch ('Wugong'), the beetle
      Mylabris phalerata Pallas ('Ban mao') and the earthworm Pheretima aspergillum
      Chen ('DiLong') have a reputation in traditional Chinese medicine for reducing
      symptoms of central nervous system decline, including memory loss. A series of
      extracts of all three organisms was tested for acetylcholinesterase (AChE)
      inhibition and copper ion binding effects, the latter likely to reduce oxidative
      damage caused by excess copper. The beetle and centipede chloroform extracts
      showed the strongest AChE inhibitory effects (30.6% inhibition at 105 microg mL(
      1) and 32.3% inhibition at 167 microg mL(-1), respectively) and, in the case of
      the centipede, this was traced to the unsaturated fatty acids present using
      bioassay-guided fractionation. Cantharidin from the beetle was shown to have AChE
      activity (31% inhibition at 1 muM, 0.196 microg mL(-1)), making it a major
      contributor to the activity of the beetle extract. The earthworm showed no AChE
      inhibitory activity. Since unsaturated fatty acids have not been previously
      reported to have AChE inhibitory activity, a series of related compounds was
      tested to determine structure-activity relationships. It was found that activity
      existed where there was a chain length of more than 16 C atoms with at least one
      unsaturated bond in the chain. The carboxylic acid group was also necessary for
      activity. The fatty acids present in the centipede also showed the ability to
      bind copper ions when tested using a novel thin layer chromatography method
      designed to detect copper-binding compounds. The activities reported give some
      support to the use of the beetle and centipede in traditional Chinese medicine
      for improving cognitive function.

PMID- 16805961
TI  - Effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats.
AB  - The purpose of this study was to investigate the effect of imatinib mesilate on
      the disposition kinetics of ciclosporin in rats. The blood concentration-time
      course and pharmacokinetic parameters of ciclosporin did not significantly change
      after intravenous injection of ciclosporin (10 mg kg(-1)) in rats treated with
      imatinib mesilate (50 mg kg(-1)) as compared with a control. When ciclosporin (10
      mg kg(-1)) was orally administered, the time course, area under the curve,
      bioavailability and peak blood concentration of ciclosporin were significantly
      increased in rats that had been treated with imatinib mesilate 2 h before
      ciclosporin administration as compared with the control. Because both drugs are
      transported via P-glycoprotein and breast cancer resistance protein and
      metabolized by cytochrome P450 3A2, the interaction of imatinib mesilate with
      these proteins may be responsible for the increased intestinal absorption of
      ciclosporin in rats. These results indicate that imatinib mesilate enhanced the
      intestinal absorption of ciclosporin in rats with only the oral administration of
      ciclosporin, suggesting that our results support clinical data. In addition,
      imatinib mesilate may increase the pharmacological effects and possibly toxicity
      of ciclosporin.

PMID- 16805962
TI  - Enhancement of availability of cloricromene at brain level by a lipophilic
      prodrug.
AB  - The pharmacokinetics of a lipophilic alkylamino acid (LAA) prodrug of
      cloricromene (AD6), name CLOR-C4, was studied in rat plasma and brain. In
      particular, we observed that the intraperitoneal administration of CLOR-C4 to
      rats was able to provide a slight but statistically significant higher
      concentration of the active drug metabolite (cloricromene acid) in the brain
      compared with the parent drug administered by the same way. The correlation
      between pharmacokinetic data and calculated partition (LogP) and brain
      distribution coefficients (LogBB) supported the hypothesis that the amphiphilic
      nature of the LAA promoiety could be responsible for a better penetration into
      the brain, more than the simple increase of lipophilicity gained with respect to
      the parent drug.

PMID- 16805963
TI  - Changes in the erythrocyte glutathione concentration in the course of diabetes
      mellitus.
AB  - This study aims to evaluate the significance of the changes of erythrocyte
      reduced glutathione (GSH) in the course of diabetes mellitus including the pre
      diabetes stage and cardiovascular disease co-morbidity. A total of 222
      participants (female:male, 107:115) were selected and their erythrocyte GSH
      levels were measured. The participants were divided into four groups: (i)
      control; (ii) those with blood glucose level > or =5.6 mmol/l but < 6.9 mmol/l as
      pre-diabetes mellitus with no other pathology; (iii) diabetes without co
      morbidity; and (iv) those with diabetes mellitus and cardiovascular disease.
      Statistical analysis was by ANOVA followed by a Fisher's LSD post hoc test. We
      observed that GSH concentration was significantly different between groups (P <
      0.04). The Fisher's post hoc test indicated significant differences in
      erythrocyte GSH levels between the pre-diabetes mellitus and diabetes mellitus
      groups compared to control (P < 0.005 and P < 0.05, respectively). A
      statistically significant change (P < 0.001) involving an initial fall followed
      by a rise in erythrocyte GSH levels was observed when diabetes mellitus and
      diabetes mellitus+cardiovascular disease groups were combined and assessed with
      respect to period of diabetes. We conclude that oxidative stress is already
      present in the pre-diabetes stage as determined by the fall in GSH, representing
      the initial phase of oxidative stress in diabetes mellitus progression. This
      finding provides evidence that antioxidant markers such as GSH could be a useful
      tool for pre-diabetes mellitus screening.

PMID- 16805964
TI  - Hydrogen peroxide inhibits activity of the IGF-1 receptor kinase.
AB  - IGF-1 receptor (IGF1R) is a transmembrane tyrosine kinase, which is indispensable
      for cellular growth and differentiation. Using a recombinant GST-tagged cytosolic
      fragment of IGF1R (GST-IGFK), we now show that oxidation by low doses (50 muM) of
      hydrogen peroxide markedly inhibits maximum phosphate incorporation in
      autophosphorylation and substrate phosphorylation assays. A similar inhibition
      was observed on the activity of intact IGF1R after treatment of T-47D cells.
      These results are in sharp contrast to the positive influence of hydrogen
      peroxide on the highly homologous insulin receptor kinase, which was assayed for
      comparison. This reciprocal influence of physiologically relevant doses of
      hydrogen peroxide may have important implications on signal transduction of the
      closely related receptors for insulin and IGF-1.

PMID- 16805965
TI  - The combined luminol/isoluminol chemiluminescence method for differentiating
      between extracellular and intracellular oxidant production by neutrophils.
AB  - To address the question why isoluminol, but not luminol, failed to detect
      oxidants produced intracellularly, differences between these luminophores were
      investigated with respect to physicochemical parameters and the character of
      chemiluminescence signal. Our results showed the isoluminol molecule to be more
      polar, more hydrophilic and possessing lower ability to form intramolecular bonds
      than the luminol molecule. Therefore, isoluminol: (i) only slightly pervaded
      biological membranes; (ii) depended essentially on extracellular peroxidase;
      (iii) did not produce chemiluminescence in the presence of extracellular
      scavengers; and (iv) it could be considered a specific detector of extracellular
      radicals. On the other hand, the physicochemical parameters of luminol and
      partial resistance of its chemiluminescence to the effect of extracellular
      inhibitors proved the lipo/hydrophilic character of this luminophore and thus its
      ability to interact with radicals both outside and inside of cells. The luminol
      chemiluminescence measured in the presence of extracellular scavengers and the
      isoluminol chemiluminescence were used with the intention to differentiate the
      effects of two antihistamine drugs on intra- and extracellular radical formation.
      In activated human neutrophils, brompheniramine inhibited the extracellular and
      potentiated the intracellular part of chemiluminescence signal, whereas a
      reducing effect of loratadine was observed in both compartments.

PMID- 16805966
TI  - Ursodeoxycholic acid in primary biliary cirrhosis improves glutathione status but
      fails to reduce lipid peroxidation.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) may slow progression in primary biliary
      cirrhosis (PBC), but its effect on survival is controversial. We have previously
      demonstrated that oxidant stress, with severely depressed plasma glutathione, is
      a feature of untreated PBC; this study examines the effect of UDCA on lipid
      peroxidation, antioxidant status and associated processes. PATIENTS AND METHODS:
      Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis,
      inflammation, cholestasis and synthetic function were measured at 0, 3, 6, 9 and
      12 months in blood and urine from 35 PBC patients receiving UDCA. RESULTS: Plasma
      glutathione, reflecting intrahepatic levels, climbed steadily on UDCA; although
      still subnormal, the median value at 12 months was 2.4-fold higher than the
      untreated level. Liver enzyme markers and C-reactive protein also improved,
      whilst PIIINP improved steadily, but the change did not attain statistical
      significance. Serum bilirubin remained unchanged and total antioxidant capacity,
      albumin and vitamin E decreased after 12 months' UDCA treatment. 8-Isoprostane
      increased and malondialdehyde was unchanged. CONCLUSIONS: UDCA treatment
      partially corrected plasma glutathione status and some other biomarkers greatly
      improved, but lipid peroxidation was not reduced. UDCA may, therefore, require
      supplementation with glutathione precursors and/or antioxidant cocktails to
      reduce oxidant stress and thus delay disease progression to cirrhosis.

PMID- 16805967
TI  - Free-radical scavenging by Ouratea parviflora in experimentally-induced liver
      injuries.
AB  - The antioxidant potential of crude extracts and fractions from leaves of Ouratea
      parviflora, a Brazilian medicinal plant used for the treatment of inflammatory
      diseases, was investigated in vitro through the scavenging of radicals 2-diphenyl
      1-picryl-hydrazyl-hydrate (DPPH), hydroxyl radical (HO*), superoxide anion (O2*
      ), and lipid peroxidation in rat liver homogenate. The crude extract (CEOP) and
      hydro-alcoholic fraction (OP4) showed strong inhibitory activity toward lipid
      peroxidation induced by tert-butyl peroxide (IC50 = 2.3 +/- 0.2 and 1.9 +/- 0.1
      microg/ml, respectively). The same products exhibited a strong concentration
      dependent inhibition of deoxyribose oxidation (14.9 +/- 0.2 and 0.2 +/- 0.1
      microg/ml, respectively), and also showed a considerable antioxidant activity
      against O2*- (87.3 +/- 0.1 and 73.1 +/- 0.4 microg/ml, respectively) and DPPH
      radicals (55.4 +/- 0.3 and 38.3 +/- 0.4 microg/ml, respectively). The protective
      effects of CEOP and OP4 were also studied in mouse liver. CCl4 significantly
      increased (by 90%) levels of lipid hydroperoxides, carbonyl protein content
      (64%), DNA damage index (133%), aspartate aminotransferase (261%), alanine
      aminotransferase (212%), catalase activity (23%), and also caused a decrease of
      60% in GSH content. The results showed that CEOP and OP4 exerted cytoprotective
      effects against oxidative injury caused by CCl4 in rat liver, probably related to
      the antioxidant activity showed by the in vitro free radical scavenging property.

PMID- 16805968
TI  - Total antioxidant capacity and the severity of the pain in patients with
      fibromyalgia.
AB  - The purpose of the study was to determine the oxidative and antioxidative status
      of plasma in patients with fibromyalgia. Total antioxidant capacity (TAC) of
      plasma was significantly lower in patients with fibromyalgia (n = 20) than in
      healthy controls (n = 20) [1.5 (SD 0.3) and 1.9 (SD 0.3) mmol Trolox equiv./l, P
      = 0.001]. In contrast, the total peroxide level of plasma was significantly
      higher in patients than in healthy controls [37.4 (SD 6.7) and 33.0 (SD 2.7)
      micromol H2O2/l; P = 0.01]. The oxidative stress index (OSI) level was
      significantly higher in patients with fibromyalgia than in healthy controls [2.5
      (SD 1.0) and 1.8 (SD 0.4); P = 0.007]. A significant negative correlation between
      visual analogue scale (VAS) and TAC level was determined (r = -0.79, P < 0.001).
      The present results indicate that patients with fibromyalgia are exposed to
      oxidative stress and this increased oxidative stress may play a role in the
      etiopathogenesis of the disease. Supplementation of antioxidant vitamins such as
      vitamins C and E to the therapy may be indicated.

PMID- 16805969
TI  - Dipyrone and aminopyrine are effective scavengers of reactive nitrogen species.
AB  - Reactive nitrogen species (RNS), namely nitric oxide (NO*) and peroxynitrite
      (ONOO-) are produced in the inflammatory sites and may contribute to the
      deleterious effects of inflammation. The aim of the present study was to evaluate
      the putative scavenging effect of a particular group of non-steroidal anti
      inflammatory drugs (NSAIDs), the pyrazolone derivatives dipyrone, aminopyrine,
      isopropylantipyrine, and antipyrine against RNS, using in vitro non-cellular
      screening systems. The results obtained showed that dipyrone and aminopyrine were
      highly potent scavengers of NO* and ONOO- while antipyrine exerted little effect
      and isopropylantipyrine no effect whatsoever against these two RNS and that, in
      the presence of bicarbonate, the scavenging potencies of both dipyrone and
      aminopyrine were slightly decreased. It could thus be inferred that the observed
      scavenging effects may be of therapeutic benefit for patients under anti
      inflammatory treatment with dipyrone and aminopyrine in the case of
      overproduction of RNS. On the other hand, the possible depletion of physiological
      NO* concentrations, namely at the gastrointestinal tract as well as the formation
      of reactive derivatives of aminopyrine and/or dipyrone, resulting from their
      reaction with RNS, may otherwise be harmful for these patients.

PMID- 16805970
TI  - [The effect of structural adjustment on health conditions in Latin America and
      the Caribbean, 1980-2000].
AB  - OBJECTIVE: To assess the impact of structural adjustment on health indicators in
      Latin America and the Caribbean during 1980-2000. METHODS: This was an ecological
      study. Public spending and per capita gross domestic product (pcGDP) figures were
      obtained from the World Bank, and life expectancy (LE) and infant mortality (IM)
      figures were obtained from the World Health Organization. Structural adjustment
      (government downsizing) was assessed by looking at the change in the amount of
      spending taken up by the government (or the reduction in public spending) in
      Latin American and Caribbean countries during 1980-1990. Changes in health
      indicators were measured in terms of the percentage variation in LE and IM. The
      variations found in Latin America and the Caribbean were compared to those seen
      in different groups of countries in other parts of the world during 1980-2000.
      Pearson's chi squared test was used to explore the associations between the
      decrease in public spending and health indicators. In order to estimate the
      health effects of such changes, a multivariate linear regression model was
      created, with adjustments for pcGDP. RESULTS: A deceleration in the rise of LE
      and in the decline of IM in Latin America and the Caribbean was noted, especially
      over the period from 1980 through 1990. Significant associations were observed
      between health indicators and the change in public spending in all groups of
      countries included in the study. When adjustments were introduced into the
      multiple regression model, the only associations that remained were seen in Latin
      America and the Caribbean. CONCLUSIONS: In the decade of 1980, adjustments in
      macroeconomic policies had a negative effect on social indicators, specifically
      those that had to do with health conditions in Latin America and the Caribbean.
      Such an effect lasted throughout the following decade.

PMID- 16805971
TI  - Utilization and purchase of medical care services in Mexico by residents in the
      United States of America, 1998-1999.
AB  - OBJECTIVES: We assessed self-reported frequency of purchase of medications and
      medical care services in Mexico by southern New Mexico (United States, [U.S.])
      residents in relation to their medical insurance coverage. METHODS: We analyzed
      data obtained in 1998 and 1999 from a health interview survey of residents in a
      six-county region of southern New Mexico, using prevalence and logistic
      regression methods for complex survey data. RESULTS: About 22% of southern New
      Mexico residents had purchased medications and 11% had sought medical care in
      Mexico at least once during the year preceding the survey. When we adjusted for
      the effects of other variables, persons able to pay for services out of pocket
      and those who were uninsured were more likely than persons who were fully covered
      to purchase medications or medical care in Mexico. CONCLUSIONS: Large numbers of
      people residing near the border in New Mexico traveled south to Mexico to
      purchase medications and medical care. Lack of medical insurance was associated
      with higher frequencies of these purchases. There seems to be a need to establish
      relationships between U.S. private and public care plans and Mexican medical care
      providers to identify appropriate mechanisms for U.S. residents to purchase
      medical care in Mexico.

PMID- 16805972
TI  - Acculturation, socioeconomic status, obesity and lifestyle factors among low
      income Puerto Rican women in Connecticut, U.S., 1998-1999.
AB  - OBJECTIVES: To examine the associations of socioeconomic status and acculturation
      with obesity and lifestyle characteristics that may be risk factors for diabetes
      and cardiovascular disease among low-income Puerto Rican women. METHODS: This
      cross-sectional study was conducted between 1998 and 1999 by interviewing a
      convenience sample of 200 low-income Puerto Rican female caretakers of young
      children in Hartford, Connecticut, United States of America. Various recruitment
      methods were used to ensure adequate representation of the target community. The
      associations of obesity (body mass index > or = 30.0) and lifestyle factors
      (physical activity, cigarette smoking, alcohol consumption, food intake) with
      socioeconomic status (education, employment, car ownership), acculturation, age,
      and marital status were examined with Spearman rho, chi-squared, and Mann-Whitney
      U tests and logistic regression analyses. RESULTS: Mean age was 29 years. Obesity
      (40%), physical inactivity (47%), and cigarette smoking (32%) were common. Less
      acculturated participants were 57% less likely to smoke and 54% less likely to be
      obese than their more acculturated counterparts. Lower socioeconomic status (not
      finishing high school or not owning a car) was associated with a higher
      likelihood of obesity, but unemployed (vs. employed) women were less likely to be
      obese (P < 0.05). Women who did not own a car consumed meat, eggs and fish less
      often than those who owned a car. Smokers were more likely to have an unhealthy
      food intake pattern than nonsmokers. CONCLUSIONS: The associations of
      acculturation and socioeconomic status with some lifestyle characteristics
      suggest the need for culturally appropriate programs to promote healthy lifestyle
      behaviors in this low-income community.

PMID- 16805973
TI  - [Economic impact of dengue and dengue hemorrhagic fever in the State of Zulia,
      Venezuela, 1997-2003].
AB  - OBJECTIVES: To determine the direct and indirect costs of medical care provided
      to cases of dengue and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)
      between 1997 and 2003 in Zulia State, Venezuela. METHODS: The total number of
      patients with dengue and DHF/DSS was obtained from records belonging to the
      Regional Epidemiology Office of the state of Zulia and from reports of cases that
      were confirmed in the Virology Section of Dr. Americo Negrette's Clinical
      Research Institute, Zulia University, Maracaibo, Venezuela, between 1 January
      1997 and 31 December 2003. Direct costs included the cost of emergency medical
      care for all cases and hospital costs for cases with DHF/DSS (cost per bed-day
      and laboratory expenses). The costs connected to absence from work among patients
      over 15 years of age and mothers who accompanied their children under 15 years of
      age comprised the indirect costs, which were adjusted for the proportion of men
      and women in the labor force. Calculations were based on the minimum yearly wage,
      and results were given in United States dollars, converted according to each
      year's average exchange rate. RESULTS: During the study period, 33,857 cases of
      dengue and DHF/DSS were seen. Of them, 30 251 (89.35%) were cases of dengue, and
      3606 (10.65%) were cases of DHF/DSS. Six cases of DHF/DSS died (lethality rate:
      0.2 per 100 cases of DHF/DSS). Direct costs were 474,251.70 US dollars; of these
      costs, 132,042.30 US dollars were spent on emergency medical care and 342,209.40
      US dollars on the hospital costs of DHF/DSS cases. Indirect costs were 873,825.84
      US dollars and comprised 64.8% of overall expenditures (1 ,48,077.54 US dollars)
      connected to this disease during the study years. CONCLUSIONS: This is the first
      study on the economic impact of dengue in the state of Zulia and in Venezuela. In
      spite of some limitations, results show that dengue is an important public health
      problem that causes great expense because of temporary absenteeism from work and
      that undermines regional and national economic development.

PMID- 16805974
TI  - [Relationship between determining factors for depressive symptoms and for dietary
      habits in older adults in Mexico].
AB  - OBJECTIVE: To determine the factors that are commonly associated with both the
      dietary habits of older adults living in the community and depressive symptoms in
      this group. METHODS: Secondary analysis of data on Mexico City obtained by means
      of the multicenter study on Health, Well-being, and Aging (Salud, Bienestar y
      Envejecimiento, SABE) that was carried out in 1999 and 2000. The following
      variables were examined: presence or absence of depressive symptoms, according to
      Yesavage's Geriatric Depression Scale (GDS); mental status, as reflected by the
      score obtained on a modified, shortened version of Folstein's Mini-mental State
      Examination (MMSE); and functional capacity, as measured by Katz' Index of
      Independence in Activities of Daily Living. Those whose score on the shortened
      MMSE was 12 points or less were asked to respond to the Pfeffer Functional
      Activities Questionnaire, which was used to assess their ability to perform the
      basic activities of daily living. Information was obtained through self-report on
      the material, physical, psychological, and social aspects of purchasing,
      preparing, and consuming food products and of oral health status during the most
      recent 12-month period. Variables that were significantly associated with the
      results obtained on the GDS were included in a multivariate regression analysis;
      several statistical models were created, and variables that were shown to be
      statistically significant in the stepwise multivariate linear regression were
      used to determine the best-fitting explanatory model for the results obtained on
      the GDS. RESULTS: The average age of study participants was 64.4 +/- 8.6 years,
      and the prevalence of depressive symptoms was 66%. The score obtained on the GDS
      showed a significant association with the presence of arterial hypertension (P <
      0.01), but not with the self-reported presence of diabetes, neoplasia, stroke,
      lung disease or heart disease. However, the use of dental prostheses (P < 0.01),
      urinary incontinence (P < 0.01), and falls (P < 0.01) were significantly
      associated with the results on the GDS. The intake of milk products, meat, fish,
      fowl, fruit, and vegetables was significantly lower in the group that had
      depressive symptoms. An inverse correlation was detected between the score
      obtained on the GDS on the one hand, and the number of complete meals consumed
      during the day (P < 0.01) and total fluid intake (P < 0.01) on the other. The
      determining factors that were most closely associated with these results were, in
      addition to the presence of arterial hypertension, the presence of cognitive
      impairment (P < 0.01), difficulty performing the basic activities of daily living
      (P = 0.03) and the instrumental activities of daily living (P < 0.01), poor
      mobility (P < 0.01), difficulty using the telephone (P < 0.01), and the self
      perception of having poor memory (P < 0.01), of having insufficient resources
      with which to live (P < 0.01), and of having poor oral health (P < 0.01). These
      variables explained 31% of the variance seen in the R2 values linked to the SDG
      variables that were incorporated into the final explanatory model. CONCLUSION: A
      number of determining factors for depressive symptoms and the results obtained on
      the GDS resemble the factors that determine poor dietary habits among older
      adults. The potential existence of common causative mechanisms calls attention to
      the need for designing interventions aimed at preventing both types of problems
      and their negative consequences. These results confirm the need to take dietary
      habits and other parameters into account when studying depression in older
      adults.

PMID- 16805975
TI  - Health disparities between island and mainland Puerto Ricans.
AB  - OBJECTIVE: To detect health disparities among three populations--Puerto Ricans
      living in Puerto Rico as well as Puerto Ricans and non-Hispanic whites living on
      the United States (U.S.) mainland. METHODS: Data from two similarly designed
      surveys conducted in 1999-2000 were analyzed. The Behavioral Risk Factor
      Surveillance System (BRFSS) provided data on Puerto Ricans living on the island
      and on non-Hispanic whites in the U.S. Another survey of Puerto Ricans living in
      New York City provided data on mainland Puerto Ricans. The age- and sex
      standardized weighted prevalences of various health parameters (e.g., obesity,
      diabetes, smoking, and physical illness) and indicators of access to health care
      (e.g., frequencies of routine checkups and diabetes care) were compared between
      populations by means of standardized rate ratios (SRR). RESULTS: Puerto Ricans
      living on the mainland and those living on the island had a similar prevalence of
      obesity (21% to 22%). Compared with islanders, mainland Puerto Ricans had a
      higher prevalence of diabetes (SRR = 1.4; 95% confidence interval [95% CI] = 1.01
      to 2.0); those with diabetes also showed higher prevalences of smoking (SRR =
      4.2; 95% CI = 2.3 to 7.7) and physical illness (SRR = 1.5; 95% CI = 1.1 to 2.0)
      than Puerto Ricans living on the island. While mainland Puerto Ricans were
      similar to non-Hispanic whites in terms of their utilization of primary
      prevention and diabetes care, island Puerto Ricans trailed behind significantly.
      CONCLUSIONS: Puerto Ricans living on the U.S. mainland and those living in Puerto
      Rico both need to target lowering their prevalence of obesity and diabetes. For
      island Puerto Ricans, improved education about the significance of primary
      prevention and diabetes care is needed. For mainland Puerto Ricans, the
      accessibility of the primary health care system renders it a potentially
      effective venue for interventions, particularly for smoking cessation. More
      studies are warranted to identify factors associated with the poor health status
      observed in mainland Puerto Ricans.

PMID- 16805976
TI  - Pneumococcal disease and vaccination in the Americas: an agenda for accelerated
      vaccine introduction.
AB  - This piece summarizes the presentations and discussions at a meeting on
      pneumococcal disease surveillance in the Americas that was held in Mexico City,
      Mexico, on 2 November 2004. This meeting was organized by the Pan American Health
      Organization (PAHO) and the Pneumococcal Vaccines Accelerated Development and
      Introduction Plan (PneumoADIP) of the Global Alliance for Vaccines and
      Immunization (GAVI). The meeting participants reviewed the status of pneumococcal
      disease surveillance in the Region of the Americas, estimates of the burden of
      pneumococcal disease, the distribution of Streptococcus pneumoniae serotypes that
      cause invasive disease, the status of pneumococcal vaccine introduction, health
      economic analyses, and financial issues related to vaccine introduction. The
      meeting participants also worked to identify the next steps for generating the
      critical information needed to help make decisions on pneumococcal vaccine
      introduction. Coordinated pneumococcal disease surveillance for the Region of the
      Americas dates back to the 1993 establishment by PAHO of the Regional System for
      Vaccines (RSV) project for surveillance of bacterial meningitis and pneumonia,
      including pneumococcal disease. Surveillance data from the RSV indicate that the
      distribution of major serotypes in the Americas has been stable over time (but
      that antibiotic resistance is increasing), with serotype 14 being the leading
      serotype isolated in most countries participating in RSV. Based on local serotype
      data from six of the RSV countries (Argentina, Brazil, Chile, Colombia, Mexico,
      and Uruguay), the 7-valent vaccine would cover 65% of serotypes, the 9-valent
      vaccine would cover 77%, and the 11-valent vaccine would cover 83%.

PMID- 16805977
TI  - [Brazilian guidelines for marketing baby food: history, limitations and
      perspectives].
AB  - The objective of this paper is to present and discuss Brazilian policy concerning
      actions to protect breastfeeding, especially the history, international and
      national background, limitations, and perspectives of the Brazilian Guidelines
      for the Marketing of Baby Food, Pacifiers and Bottles. The Brazilian Guidelines,
      which play a crucial role in protecting breastfeeding against industry marketing
      strategies, were based on the International Code of Marketing of Breastmilk
      Substitutes, proposed by the World Health Organization in 1981. The first version
      of the Brazilian Guidelines was released in 1988, and there were subsequent
      revisions in 1992 and 2001/2002. In 2006, the Guidelines became national law.
      However, the strides made over this period in terms of regulation have been few
      because the law is not always observed. Thus, it is essential that all actors
      involved, including government officials, manufacturers and sellers of baby food
      and other baby products, teaching and health professionals and their
      associations, international bodies, and non-governmental organizations make a
      commitment to enforce the current law.

PMID- 16805978
TI  - Current status and correlated issues on cochlear implantation.

PMID- 16805979
TI  - Cochlear function after selective spiral ganglion cells degeneration induced by
      ouabain.
AB  - BACKGROUND: Ouabain, a cardiac glycoside that specifically binds to Na/K-ATPase
      and inhibits its activity, was applied to gerbils to develop a method for
      studying auditory neuropathy. METHODS: Ouabain was applied to the round window of
      the cochlea in each gerbil by using a piece of gelfoam with 3 microl or 24 microl
      (1 mmol/L) ouabain solution. The changes of the threshold of auditory brainstem
      response, cochlear function round window electrocochleography, as well as the
      morphological changes of the spiral ganglion cells of the cochlea were observed
      after application of ouabain for 24 hours or 96 hours. RESULTS: In ouabain
      treated gerbils, auditory brainstem response and compound action potential
      thresholds showed either elevation or no response at all. However, the thresholds
      of cochlear microphonic and distortion product otoacoustic emissions were not
      affected. Degeneration and necrosis of some spiral ganglion cells in ears with
      applications of ouabain (24 hours, 3 microl, 1 mmol/L; 96 hours, 24 microl, 1
      mmol/L ouabain). The number of spiral ganglion cells was decreased (24 hours, 3
      microl, 1 mmol/L ouabain) or near to a total loss (96 hours, 24 microl, 1 mmol/L
      ouabain). CONCLUSIONS: These results indicate a high degree of independence
      between the spiral ganglion cells and the outer hair cell systems in the cochlear
      transduction mechanism. The method used in this study would provide a valuable
      tool for studying auditory neuropathy.

PMID- 16805980
TI  - Aminoglycoside ototoxicity in three murine strains and effects on NKCC1 of stria
      vascularis.
AB  - BACKGROUND: After establishing a murine model of aminoglycoside antibiotic (AmAn)
      induced ototoxicity, the sensitivity of AmAn induced ototoxicity in three murine
      strains and the effect of kanamycin on the expression of Na-K-2Cl cotransporter-1
      (NKCC1) in stria vascularis were investigated. METHODS: C57BL/6J, CBA/CaJ,
      NKCC1(+/-) mice (24 of each strain) were randomly divided into four experimental
      groups: A: kanamycin alone; B: kanamycin plus 2, 3-dihydroxybenzoate; C: 2, 3
      dihydroxybenzoate alone; and D: control group. Mice were injected with kanamycin
      or/and 2, 3-dihydroxybenzoate twice daily for 14 days. Auditory brainstem
      response (ABR) was measured and morphology of cochlea delineated with succinate
      dehydrogenase staining. Expression of NKCC1 in stria vascularis was detected
      immunohistochemically. RESULTS: All three strains in groups A and B developed
      significant ABR threshold shifts (P < 0.01), which were accompanied by outer hair
      cell loss. NKCC1 expression in stria vascularis was the weakest in group A (A cf
      D, P < 0.01) and the strongest in groups C and D (P < 0.05). CBA/CaJ mice had the
      highest sensitivity to AmAn. CONCLUSIONS: Administration of kanamycin established
      AmAn induced ototoxicity. Kanamycin inhibited the expression of NKCC1 in stria
      vascularis. 2, 3-dihydroxybenzoate attenuated AmAn induced ototoxicity-possibly
      by enhancing the expression of NKCC1. Age related hearing loss did not show
      additional sensitivity to AmAn induced ototoxicity in murine model.

PMID- 16805981
TI  - Comparison of three methods for isolation of nucleic acids from membranate inner
      ear tissue of rats.
AB  - BACKGROUND: Mitochondrial DNA mutations have been found in sensorineural
      deafness. The aim of this study was to compare three methods for extraction of
      nucleic acid from membranate inner ear tissue of rats. METHODS: Alkaline
      denaturation, a conventional phenol-chloroform method and Trizol reagent were
      respectively used to extract the slight nucleic acid from membranate inner ear
      tissue of rats. We assessed the amount and quality of nucleic acid using a UV
      spectrometer and polymerase chain reaction (PCR). RESULTS: The yield and purity
      (OD260/OD280) of DNA from inner ear tissue using the phenol-chloroform method was
      the highest of the three methods. Mitochondrial DNA (mtDNA) fragment can be
      amplified by PCR from nucleic acid prepared by all methods, while no nuclear DNA
      (nDNA) fragment can be amplified by method of alkaline denaturation. Both nuclear
      and mitochondrial genes could be amplified by reverse transcriptional PCR from
      the RNA prepared by Trizol reagent. CONCLUSION: Adequate amount and high-quality
      of mtDNA, nDNA and RNA were obtained from unilateral membranate inner ear tissue
      of rats. Method of alkaline denaturation could be chosen when mtDNA without nDNA
      was needed, while phenol-chloroform method was suitable for extracting total DNA
      (including nDNA and mtDNA); method with Trizol reagent was suitable for
      extracting total RNA and total DNA.

PMID- 16805982
TI  - Intranasal application of Epstein-Barr virus/lipoplex to abrogate eosinophillia
      in murine model of allergic rhinitis.
AB  - BACKGROUND: Currently anti-inflammatory therapy with steroids for allergic
      rhinitis need long-term repeated administration, although it is effective. Gene
      therapy is being suggested to substitute it. The aim of this study was to
      investigate nonviral vector mediated exogenous gene expression in COS-7 cells in
      vitro and the effect of intranasal mouse interleukin (mIL)-12 transgene
      expression on allergen induced eosinophil infiltration of nasal mucosa in a
      murine model of allergic rhinitis. METHODS: In vitro COS-7 cells were infected
      with Epstein-Barr virus (EBV)/lipoplex. The expression of IL-12 p70 in cell
      culture supernatant was examined by enzyme-linked immunosorbent assay (ELISA). In
      mice with ovalbumin (OVA) induced allergic rhinitis, EBV/lipoplex was
      administered by nasal drops before OVA challenge once a day from day 1 to day 10.
      The expression of IL-12 mRNA and protein, the change of eosinophil count in nasal
      mucosa and serum total IgE were measured 24 hours after the last challenge.
      RESULTS: EBV/lipoplex could effectively transfect COS-7 cells. The expression of
      IL-12 p70 in cell culture supernatant was significantly more than in blank
      control. IL-12 via EBV plasmid vector transduction could be overexpressed in
      vivo. In pGEG.mIL-12 treated models, the nasal mucosa revealed a high level of
      widespread mIL-12 transduction by immunohistochemistry and in situ hybridization.
      Histological evaluation revealed marked suppression of eosinophil infiltration in
      nasal mucosa. The eosinophil count in allergic rhinitis group [(26.5 +/-
      9.8)/high-power field (HPF)] was significantly increased over control group
      [(0.40 +/- 0.52)/HPF] (F = 56.94, P < 0.01), while the count in IL-12 gene
      therapy group [(4.60 +/- 2.63)/HPF] was significantly less than that of allergic
      group (F = 56.9, P < 0.01). Serum total IgE between in gene therapy mice [(88.83
      +/- 6.71) ng/ml] and allergic rhinitis mice [(103.1 +/- 5.7) ng/ml] showed a
      significant difference (F = 1216, P < 0.05). CONCLUSIONS: Nonviral EBV plasmid
      vector, pGEG.mIL-12 was able to overexpress exogenous gene both in vitro and in
      murine nasal mucosa in vivo. IL-12 overexpression via EBV/lipoplex could stem
      allergen induced eosinophil infiltration in nasal mucosa in murine models of
      allergic rhinitis, which may suggest a new cytokine immunogenetic therapy for
      allergic rhinitis.

PMID- 16805983
TI  - Changes of the proportion and mortality of pulmonary thromboembolism in
      hospitalized patients from 1974 to 2005.
AB  - BACKGROUND: Pulmonary thromboembolism (PTE) has become a common disease that
      severely endangers people's health. This study analysed the changes in proportion
      and mortality of PTE in hospitalized patients to provide data for prevention and
      management of the disease. METHODS: The data of 763 hospitalized patients with
      PTE from 1974 to 2005 in Fuwai Hospital were analysed. RESULTS: During the 1970s,
      0.27% of patients in a cardiovascular hospital had PTE (< 5 cases per year);
      while so far this century the proportion is 0.94% (48 to 113 per year). The
      mortality of hospitalized PTE patients fell from 20.00% in the 1970s to 4.10%
      this century. Prior to 1990, the mortality of hospitalized PTE patients was
      12.50%, and in the years after 1990 only 3.40%. The difference was statistically
      significant (P < 0.005). People with this disease were mostly between the ages of
      30 and 69 years. Men were most susceptible between the ages of 30 and 69 years,
      while women between the ages of 40 and 69 years. Men contracted PTE 10 years
      earlier than women. The mortality of male PTE patients was 4.70%, not
      significantly different from female patients, 5.06% (0.50 < P < 0.75). There were
      not any significant differences between the mortality of patients in the
      different age groups overall (< or = 39, 40 - 49, 50 - 59, and > or = 60 years, P
      > 0.1). More people contracted the disease in winter than in other seasons (P <
      0.05). There was no obvious difference between the mortality in different seasons
      overall (0.75 < P < 0.90). CONCLUSION: PTE is an increasingly significant disease
      and deserves adequate attention.

PMID- 16805984
TI  - Early experiences on living donor liver transplantation in China: multicenter
      report.
AB  - BACKGROUND: Because of the lack of brain death laws in China, the proportion of
      cadaveric organ donation is low. Many patients with end-stage liver disease die
      waiting for a suitable donor. Living donor liver transplantation (LDLT) would
      reduce the current discrepancy between the number of patients on the transplant
      waiting list and the number of available organ donors. We describe the early
      experience of LDLT in the mainland of China based on data from five liver
      transplant centers. METHODS: Between January 2001 and October 2003, 45 patients
      with end-stage liver disease received LDLT at five centers in China. The
      indication and timing, surgical techniques and complications, nonsurgical issues
      including rejection, infection, and advantages of LDLT in the series were
      reviewed. Actuarial patient and graft survival rates were calculated by using the
      Kaplan-Meier product-limit estimate. Statistical analysis was completed by using
      SPSS 10.0. RESULTS: All LDLT recipients were cirrhotic patients, except for one
      man with fulminant hepatic failure. Among the 45 cases of LDLT, 35 (77.8%) were
      performed in one center (the First Affiliated Hospital of Nanjing Medical
      University). The overall 1 and 3 year survival rate of the recipients was 93.1%
      and 92.0%, respectively. Of the 45 LDLT donors, there were 3 cases of biliary
      leakage, 2 subphrenic collections, 1 fat liquefaction around the incision and 1
      biliary peritonitis after T tube removal. All donors recovered completely.
      CONCLUSIONS: LDLT provides an excellent approach to addressing the problem of
      donor shortage in China even though the operation is complicated, uncompromising
      and difficult with respect to the safety of the donors and receptors. Despite
      early technical hurdles having been overcome, perfection of technique is still
      necessarily. At present, LDLT is a good choice for the patients with irreversible
      liver disease.

PMID- 16805985
TI  - Connective tissue growth factor is associated with the early renal hypertrophy in
      uninephrectomized diabetic rats.
AB  - BACKGROUND: Renal hypertrophy has been regarded as the early feature of diabetic
      nephropathy (DN), which may eventually lead to proteinuria and renal fibrosis.
      However, the exact mechanism of renal hypertrophy is still unclear. The aim of
      this study was to investigate the possible association of connective tissue
      growth factor (CTGF) with renal hypertrophy in uninephrectomized diabetic rats.
      METHODS: Seventy-two Sprague-Dawley (SD) rats were randomly divided into two
      groups: control group (group C, n = 32) and diabetic nephropathy (group DN, n =
      40). Each group was re-divided into 4 subgroups according to the experimental
      period. The rats were sacrificed at 1, 2, 4, and 8 weeks respectively after
      induction of diabetes. Diabetes was induced by intraperitoneal injection of
      streptozotocin (STZ) after rats had received uninephrectomy. Blood glucose (BG),
      body weight (BW), 24-h urinary albumin excretion (24hUalb), kidney weight (KW),
      KW/BW, glomerular tuft area (AG), glomerular tuft volume (VG), proximal tubular
      area (AT) at each time point, the width of glomerular basement membrane (GBM) and
      tubular basement membrane (TBM) at week 8 were measured when the rats were
      sacrificed. Renal expression of CTGF and p27kip1 were detected by
      immunohistochemical staining. The relationship between CTGF expression and
      increasing of VG and AT was analyzed. RESULTS: There was a significant increase
      of 24hUalb, KW, and KW/BW from week 1 onward in diabetic rats compared to those
      in group C (P < 0.05, respectively), diabetic rats also had a significant
      increase of AG, VG, and AT from week 1 onward. It was also shown that diabetic
      rats had a thickening of GBM [(245.7 +/- 103.0) nm vs (121.8 +/- 19.1) nm, P <
      0.01] and TBM [(767.7 +/- 331.1) nm vs (293.0 +/- 110.5) nm, P < 0.01] at week 8.
      There was a weak expression for CTGF and p27kip1 in normal glomeruli and tubuli,
      while a significant increasing expression of CTGF and p27kip1 was found in
      glomeruli and tubuli in diabetic kidney from week 1 onward (P < 0.05,
      respectively), and the extent of CTGF expression was positively correlated with
      AG (r = 0.92, P < 0.05), VG (r = 0.86, P < 0.05), AT (r = 0.94, P < 0.01) and
      positively correlated with the expression of p27kip1 (r = 0.96, P < 0.01).
      CONCLUSION: The expression of CTGF increases in diabetic rat kidney at the early
      stage, which might be an important mediator of renal hypertrophy through
      arresting cell cycling.

PMID- 16805986
TI  - Interleukin-16 in asthma.

PMID- 16805987
TI  - BrdU-labelled neurons regeneration after cerebral cortex injury in rats.

PMID- 16805988
TI  - Effects of co-engraftment of Schwann cells with neural stem cells into rats with
      Parkinson disease.

PMID- 16805989
TI  - HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses
      against HIV-1 infection in mice.

PMID- 16805990
TI  - Influence on the immune function of the human peripheral blood mononuclear cells
      transfected by retrovirus-mediated HSV-tk gene.

PMID- 16805991
TI  - Pro-apoptotic effect of cecropin AD on nasopharyngeal carcinoma cells.

PMID- 16805992
TI  - Initial experience with circumferential pulmonary vein ablation guided by fusion
      of magnetic resonance imaging with three-dimensional electroanatomic mapping.

PMID- 16805993
TI  - Neurilemmomas of the nasal vestibule: report of two cases.

PMID- 16805994
TI  - Can green tea protect against not only sunburn but also melanoma?

PMID- 16805995
TI  - [Clone and expression of murine BTLA extracellular domain gene and its effect on
      the expression of B7 on dendritic cells].
AB  - AIM: To study the regulatory effect of recombinant glutathione S-transferase
      (GST)-extracellular domain of murine B and T lymphocyte attenuator (mBTLAext)
      fusion protein GST-mBTLAext on the expression of B7 on murine dendritic cell (DC)
      line DC2.4. METHODS: cDNA of mBTLA was amplified from total RNA of murine
      splenocytes by RT-PCR. The recombinant prokaryotic expression vector pGEX-4T
      2/mBTLAext was constructed by cloning mBTLAext into pGEX-4T-2 and then
      transformed into E. coli BL21 (DE3). The fusion protein GST-mBTLAext was
      expressed under the induction of 1 mmol/L IPTG, and then was extracted from
      inclusion body and purified through Glutathione Sepharose 4B chromatography
      column. The fusion protein was added into the culture supernatant of DC2.4 and
      its effect on the expression of B7-1 and B7-2 on DC2.4 was analyzed by flow
      cytometry. RESULTS: The recombinant prokaryotic expression vector pGEX-4T
      2/mBTLAext was constructed and the fusion protein GST-mBTLAext was expressed
      successfully. The molecular weight of the fusion protein was 43.0 kDa, determined
      by SDS-PAGE, which was corresponding to expectation. GST-mBTLAext could up
      regulate the expression of B7-1, but didn't alter the expression of B7-2, on
      DC2.4 in a dose dependent manner. CONCLUSION: BTLA had a regulatory effect on the
      expression of B7 on DC. It is significant to study the effect of BTLA on the
      biological behaviour of DC and its molecular mechanism.

PMID- 16805996
TI  - [Isolation and function analysis of rat CD4+ CD25+ regulatory T cells].
AB  - AIM: To investigate the isolation method and to analyze the function of rat
      CD4(+) CD25(+) regulatory T cells. METHODS: Lymphocytes were isolated from the
      rat spleens and then CD4(+) CD25(+) T cells were sorted by magnetic bead cell
      sorting (MACS) system. The purity and Foxp3 expression of CD4(+) CD25(+) T cells
      were analyzed by flow cytometry(FCM) and RT-PCR, respectively. The suppressive
      effect of CD4(+) CD25(+) T cells on the proliferation of CD4(+) CD25(-) T cells
      was analyzed by mixed lymphocyte reaction. IL-2, IFN-gamma and IL-10 levels in
      culture supernatant were detected by ELISA. RESULTS: The purity of CD4(+) CD25(+)
      T cells sorted by MACS was 86%-93%. The CD4(+) CD25(+) T cells could specifically
      express the Foxp3 gene as compared with CD4(+) CD25(-) T cells. In vitro CD4(+)
      CD25(+) T cells could suppress the proliferation of CD4(+) CD25(-) T cells and
      IFN-gamma, IL-2 production, but they themselves could secrete IL-10. CONCLUSION:
      We established an effective procedure for enrichment of CD4(+) CD25(+) regulatory
      T cells by MACS with satisfactory cell purity, viability and function. CD4(+)
      CD25(+) T cells can suppress CD4(+) CD25(-) T cells and specifically express
      Foxp3 gene.

PMID- 16805997
TI  - [Construction and application of retroviral vector system useful for high
      efficiency transfection into human T cells].
AB  - AIM: To construct a retroviral vector system with high-efficiency transfection
      into human T cells and carrying a rapid screening label, and compare it with the
      traditional retroviral vector system. METHODS: Retroviral vector pCMMP-IRES-GFP
      was first constructed by inserting the internal ribosome entry site-green
      fluorescent protein (IRES-GFP) cDNA into retroviral vector pCMMP. The chimeric
      TCR gene was inserted into pCMMP-IRES-GFP and then co-transfected into packaging
      cell line 293T with other two assistant vectors pMD. MLVgag. pol and pHDM. G.
      After 48 h, the culture supernatant was harvested and condensed by
      centrifugation. Meanwhile, the chimeric TCR gene was inserted into pLXSN and then
      transfected into packaging cell line PA317. The transfected PA317 cells were
      obtained by G418 pressure screening. The cells culture supernatant containing
      viruses was harvested after being cultured for 48 h. The viral titer was
      determined by NIH3T3 cells infection. The preactivated primary human T
      lymphocytes were infected by appropriate volume of viral fluid and detected by
      fluorescent microscopy or flow cytometry after 48 h. RESULTS: A retroviral vector
      pCMMP-IRES-GFP was constructed successfully. Compared with the traditional vector
      system, the viral titer was 2.15x10(11) VP/L vs 6.43x10(9) VP/L, and efficiency
      of transfection into preactivated primary T cells was 50%-60% vs 5%-10%.
      Furthermore, the infected cells were also detected by fluorescent microscope and
      could sorted by fluorescent activated cell sorting. CONCLUSION: A retroviral
      vector system with high transfection efficiency into T lymphocytes and carrying a
      rapid screening label has been constructed, which establishes the foundation for
      basic and clinical studies on T lymphocytes.

PMID- 16805998
TI  - [Expression and identification of HCV core protein in human hepatocytes].
AB  - AIM: To construct the recombinant plasmid of HCV core protein, and to express and
      identify it in normal human hepatocyte HL-7702. METHODS: HCV core gene was cloned
      by using PCR from plasmid pBRTM/HCV1-3011 which included the full length of HCV
      gene. The core segment with expression plasmid pcDNA3.1(-) was recombined to
      construct eukaryotic expression plasmid pcDNA3.1(-)/core, which was then
      transfected into human hepatocytes by using poly-cation. The expression of core
      protein was detected by immunochemical staining and Western blot. RESULTS: The
      length and sequence of the cloned core segment were correct. The transfected HL
      7702 cells expressed the core protein. CONCLUSION: The eukaryotic expression
      plasmid pcDNA3.1(-)/core including HCV core gene is successfully constructed. The
      effective expression of HCV core protein in human hepatocytes is useful for
      further development of HCV core antigen.

PMID- 16805999
TI  - [Construction of the transfected cell line expressing the human CXCR4 gene and
      study of its biological function].
AB  - AIM: To construct the tranfected cell line expressing the human CXCR4 gene and to
      study the biological function. METHODS: The total RNA was isolated from
      peripheral blood mononuclear cell (PBMC) with TRIzol, and the CXCR4 gene was
      amplified by RT-PCR, then digested with restriction endonuclease Pst I and EcoR
      I, and inserted into retrovirus vector pEGZ-Term. The recombinant vector together
      with its two helper virus vectors was co-transfected into the package cells 293T
      with LipofectAMINE 2000. Then the supernatant of the 293T cell culture was used
      to infect L929 cells, the cell clones stably expressing the CXCR4 molecule were
      screened in the presence of Zeocin (500 mg/L) after 72 h cultivation. RESULTS: It
      was found that the full-length of CXCR4 gene was successfully cloned, and the
      recombinant retrovirus vector carrying the CXCR4 gene was constructed. The CXCR4
      cDNA transfected L929 cell could stably express the human CXCR4 on the cell
      membrane, and the migration ability of transfected cells was well evidenced in
      the transwell system induced by SDF-1alpha after the transfection with CXCR4.
      CONCLUSION: The CXCR4 transfected L929 cell line was successfully established,
      and it can make the basis for the further research.

PMID- 16806000
TI  - [Inducement of cytotoxic T cell responses in mice by constructing a multi-CTL
      epitope-based DNA vaccine].
AB  - AIM: To construct a multi-CTL epitope-based DNA vaccine to induce specific CTL
      responses. METHODS: Multi-CTL epitope gene which encoded two HCV epitopes(H-2(d))
      was cloned into the eucaryotic expression vector pcDNA3.1 to construct a multi
      CTL epitope-based DNA vaccine. BALB/c mice were vaccinated with the DNA vaccine
      and the specific CTL responses to target cells (P815, H-2(d)) pulsed by different
      CTL epitope peptide were detected. RESULTS: The multi-CTL epitope-based DNA
      vaccine which directed against two HCV CTL epitopes induced specific CTL
      responses to each of the two CTL epitopes independently and enhanced the total
      specific CTL response. CONCLUSION: The multi-CTL epitope-based DNA vaccine is
      constructed by using multi-CTL epitopes linked as encoding sequence through
      natural flanking amino acid residues. It can not only induce specific CTL
      responses to each CTL epitope independently but also enhance the total specific
      CTL response.

PMID- 16806001
TI  - [Immune modulatory effects of mesenchymal stem cells on T lymphocytes in mixed
      lymphocyte culture].
AB  - AIM: To investigate the features of immune modulatory function derived from the
      interaction of mesenchymal stem cells (MSC) with T lymphocytes in vitro. METHODS:
      Normal human bone marrow mononuclear cells were isolated by Ficoll-Hypaque
      density gradient, then ex vivo MSCs were cultured, expanded, and obtained after
      the third passage. The MSCs were added to the two-way mixed lymphocyte culture
      (MLC) according to different proportion. On day 3 and 5, proliferation of T
      lymphocytes in each group of MLC-MSC and ctrl-MLC was measured with MTT
      colorimetry. The surface phenotypes of T lymphocytes were analyzed by flow
      cytometry before and after co-culture of MLC with MSC. RESULTS: MLC added with
      MSC induced dose- and time-dependent inhibition of T lymphocytes proliferation.
      CD4(+) T cell subsets were not suppressed so obviously as CD8(+) T cell subsets.
      CD25 expression of T lymphocytes appeared to be lower in MLC-MSC than in ctrl
      MLC. But the CD4(+) CD25(+) double positive cells were evidently increased versus
      control cultures without MSC. The HLA-DR of activated T lymphocytes was slightly
      decreased compared to the control. CONCLUSION: MSC can significantly suppress T
      lymphocytes' proliferation, especially CD8(+) T cell subsets (CTL). In addition,
      it can down-regulate the expression of some special surface marker, such as CD25
      and HLA-DR, on the activated T lymphocytes.

PMID- 16806002
TI  - [Elevation of IFN-gamma transcription level in peripheral blood mononuclear cells
      of EIAV vaccinated horses].
AB  - AIM: To evaluate the relationship between the transcriptional level of IFN-gamma
      mRNA in peripheral blood mononuclear cells (PBMC) and immune protective response
      driven by inoculated horses with donkey leukocyte attenuated vaccine of
      EIAV(DLV), and to elucidate the immune mechanism of DLV. METHODS: A real-time PCR
      method was established for quantitative detection of IFN-gamma mRNA level from
      horse PBMCs. Twelve horses were divided into vaccination group, healthy control
      group, challenging control group and EIAV natural infection group. The
      transcriptional level and distribution of IFN-gamma mRNA in PBMCs were analyzed.
      The temperature and other parameters of the inoculated horses were monitored or a
      daily basis. Horses inoculated with DLV vaccines were challenged post-inoculated
      8 months, and the change of transcriptional level of IFN-gamma mRNA during
      pre/post-challenge was evaluated. RESULTS: Compared with the healthy control and
      natural infection group. The transcriptional level of IFN-gamma mRNA was much
      higher in vaccination group (P<0.01), and kept increasing even after challenging
      with virulent EIAV strains. In the challenging control group, the transcriptional
      level of IFN-gamma mRNA fluctuated with the development of disease and reduced
      markedly during febrific episodes. CONCLUSION: This study for the first time
      reveals that EIAV-attenuated vaccine could induce high level transcription of IFN
      gamma mRNA, with is associated closely with immune protective response induced by
      DLV. This finding provides some clues to elucidate the mechanism of immunity
      protection of DLV at the molecular level.

PMID- 16806003
TI  - [Cloning, expression and identification of catalase of Helicobacter pylori].
AB  - AIM: To construct the recombinant plasmid containing catalase (KatA) of
      Helicobacter pylori (Hp), analyze its nucleic acid sequence, express it in E.
      coli and study its antigenicity. METHODS: KatA fragments were amplified from Hp
      chromosomal DNA by PCR. Its T-A was cloned, sequenced and compared with other HP
      strains on the GenBank. Then the gene cloned into pGEX-4T-1 fusion expression
      vector was expressed in E. coli and purified by GST-affinity chromatography. The
      purified product was used to identify 29 stains of mouse anti Hp monoclonal
      antibodies and analyze antigenicity with serum of Hp-infected patients by Western
      blot. RESULTS: KatA fragments were composed of 1,515 bp (GenBank No. DQ333889)
      and the nucleotide homology with other Hp strains on the GenBank was 96%-97%. 85
      kDa of the recombinant KatA-pGEX-4T-1 was expressed in E. coli. 4 of 29 anti-Hp
      mouse monoclonal antibodies were against KatA. Western blot analysis proved that
      KatA was specifically recognized in the serum of Hp-infected patients.
      CONCLUSION: The recombinant KatA has original antigenicity. It is of great value
      to clinical sero-diagnosis and vaccine study of Hp.

PMID- 16806004
TI  - [Immune response and protective efficacy induced by fusion protein ESAT6-CFP10 of
      M.tuberculosis in mice].
AB  - AIM: To study murine humoral and cellular immune response induced by fusion
      protein ESAT6-CFP10 and to examine its protective efficacy against M.
      tuberculosis (MTB) in mice. METHODS: BALB/c mice were immunized subcutaneously on
      the back with fusion protein ESAT6-CFP10 that was transferred to nitro cellulose
      (NC) membrane beforehand. Stimulation index (SI) of the spleen lymphocytes of the
      immunized mice was measured by MTT colorimetry. The level of IFN-gamma and IL-2
      and CTL upon antigen-specific stimulation were detected. The vaccinated BALB/c
      mice were intravenously infected with MTB H37Rv (10(5) CFU/mouse). Four weeks
      later the number of CFU in spleens was determined. RESULTS: The titer of serum
      specific antibody in BALB/c mice immunized with fusion protein ESAT6-CFP10 was
      1:6,400. The SI of fusion protein immunized group (1.90+/-0.15) was significantly
      higher than that of saline-immunized group (0.9+/-0.15). The level of IFN-gamma
      and IL-2 induced by the fusion protein was 1.792+/-19 ng/L and 0.211+/-11 ng/L
      respectively, which was significantly higher than that of saline-immunized group
      and lower than that of BCG-immunized group. The specific killing activity of
      splenocytes was 36%. Compared with the saline-immunized mice (bacterial load was
      6.51+/-0.13), MTB number (bacterial load was 5.24+/-0.15) was reduced
      dramatically in the spleens of BALB/c mice immunized with the fusion protein, but
      the protective efficacy of the mice immunized with BCG was higher than that of
      ESAT6-CFP10 vaccinated group. CONCLUSION: Fusion protein ESAT6-CFP10 can be used
      as a candidate for novel vaccines.

PMID- 16806005
TI  - [Cloning of human NKG2D gene and its expression in CHO cells].
AB  - AIM: To construct a recombinant eukaryotic expression vector of human NK cell
      receptor NKG2D, and express the recombinant human NKG2D in CHO cells. METHODS: A
      NKG2D gene fragment, with a length of about 650 bp, was amplified from the NK-92
      cell line by RT-PCR and was cloned to plasmid pGEM-T Easy. Then the cloned DNA
      fragment was sequenced. The recombinant plasmid pGEM-T Easy/NKG2D was digested
      with EcoR I and BamH I, and then NKG2D fragment was isolated and inserted into
      the corresponding restriction site on eukaryotic expression vector pEGFP-N1. The
      Lipofectin was used to transfect the recombinant eukaryotic expression plasmid in
      CHO cells. The expression level of NKG2D gene in transfected CHO cells was
      detected by fluorescence microscope, RT-PCR, Western blot and immunohistochemical
      staining. RESULTS: The length of cDNA fragment amplified by RT-PCR was consistent
      with that of NKG2D. DNA sequencing of pGEM-T Easy/NKG2D revealed that the cloned
      DNA sequence was identical to that of reported NKG2D. Green fluorescence was seen
      in transfected CHO cells by fluorescence microscope. Human NKG2D mRNA was highly
      expressed in transfected CHO cells. Western blot and Immunohistochemical staining
      detection showed that NKG2D was expressed in transfected cells. CONCLUSION: A
      recombinant eukaryotic expression vector of human NKG2D can be constructed and it
      can be expressed successfully in CHO cells.

PMID- 16806006
TI  - [Establishment of an HHCC cell line stably transfected by tumor antigen MAGE-3
      gene and its mRNA expression].
AB  - AIM: To construct the eukaryotic expression vector of tumor antigen MAGE-3 and
      establish human hepatocellular carcinoma cell line (HHCC) expressing MAGE-3.
      METHODS: The MAGE-3 gene was amplified by PCR and cloned into the eukaryotic
      expression vector pIRES2-EGFP to construct the pIRES2-EGFP-MAGE-3 plasmid. The
      recombinant plasmid pIRES2-EGFP-MAGE-3 was transfected into HHCC cells by
      lipofectamine, and then the positive clones were screened by G418. The expression
      of enhanced green fluorescent protein (EGFP) and MAGE-3 mRNA in positive clones
      were detected by fluorescence microscope and RT-PCR, respectively. RESULTS: The
      eukaryotic expression vector pIRES2-EGFP-MAGE-3 was successfully constructed. The
      expression of EGFP was found by fluorescence microscope detection and MAGE-3 mRNA
      transcription was detected by RT-PCR in the positive clones. CONCLUSION: The
      stable MAGE-3-transfected HHCC cell line is successfully established, which will
      provide experimental basis for further study on immunotherapy for hepatocellular
      carcinoma using MAGE-3 as target antigen.

PMID- 16806007
TI  - [Role of Wnt/beta-catenin signaling transduction pathway in rat
      hepatocarcinogenesis].
AB  - AIM: To investigate the role of Wnt/beta-catenin signaling transduction pathway
      in rat hepatocarcinogenesis. METHODS: The mRNAs of Wnt1, beta-catenin, APC,
      cyclin D1 and c-myc genes were amplified by using of semiquantitative reverse
      transcription polymerase chain reaction (RT-PCR) from normal rat livers, atypical
      hyperplasia livers and hepatoma tissues, respectively. Then the proteins
      expression of beta-catenin, APC and cyclin D1 was examined by immunohistochemical
      staining. RESULTS: In normal rat livers, the mRNAs of Wnt1, cyclin D1 and c-myc
      genes were not detected and only beta-catenin protein was observed to have low
      expression at cellular membrane. However, 14 weeks after cancer induction in
      atypical hyperplasia livers, beta-catenin protein and APC protein were
      accumulated in cytoplasm. Meanwhile, cyclin D1 protein was detected in cytoplasm
      and/or nucleus in some cells. 16 weeks after cancer induction in hepatoma
      tissues, the mRNAs and protein expression of beta-catenin, APC, cyclin D1 and c
      myc genes were detected except Wnt1. CONCLUSION: The activation of Wnt/beta
      catenin signaling transduction pathway might be one of the reasons for rat
      hepatocarcinogenesis.

PMID- 16806008
TI  - [Anti-tumor effect of monkshood polysaccharide with adriamycin long circulating
      temperature-sensitive liposome and its mechanism].
AB  - AIM: To observe the synergic action of monkshood polysaccharide (MPS) and
      adriamycin (ADM) long circulating temperature-sensitive liposome (ALTSL) in
      targeting therapy for H22 tumor-bearing mice and explore the mechanism. METHODS:
      The anti-tumor activity was evaluated by using the tumor's weight as an index.
      The life prolongation rate of mice was calculated according to the survival time
      of the tumor-bearing mice. The killer activity of NK cells and the lymphocyte
      transformation rate were detected by the LDH release assay and MTT colorimetry,
      respectively. The apoptosis of tumor cells and the expressions of p53, Fas, Fas-L
      and caspase-3 were analyzed by flow cytometry. The expressions of IL-2 mRNA and
      IL-12 mRNA in spleen lymphocytes were determined by RT-PCR. The pathologic
      changes of tumor, heart, liver and kidney tissues of the tumor-bearing mice were
      observed under light microscope. RESULTS: Compared with the adriamycin liposome
      group, the anti-tumor effects were enhanced in (MPS+ALTSL) group with tumor
      growth inhibitory rate up to 80.4%. The survival time of the tumor-bearing mice
      in ALTSL and (MPS+ALTSL) groups was significantly prolonged compared with the ADM
      group (P<0.01). The killer activity of NK cells was higher in ALTSL group than in
      the NS and ADM groups, and was highest in (MPS+ALTSL) group. The lymphocyte
      transformation rate of (MPS+ALTSL) group was markedly increased (P<0.01) as
      compared with the ADM group. The result of RT-PCR indicated that the expressions
      of IL-2 mRNA and IL-12 mRNA in lymphocytes in the adriamycin long circulating
      liposome (ALCL) group were significantly higher than those in the ADM group.
      Expressions of IL-2 mRNA and IL-12 mRNA was much higher in (MPS+ALTSL) group than
      in ALTSL group. The pathological examination indicated that in (MPS+ALTSL) group,
      more lymphocytes and monocytes were found in tumor tissue. CONCLUSION: ALTSL can
      increase the anti-tumor effect and decrease the side-effects (such as the
      cytotoxicity) of ADM. MPS combined with ALTSL can enhance killer activity of NK
      cells and transformation of T cells, supporting their synergic anti-tumor effect.

PMID- 16806009
TI  - [Effects of bcl-2 antisense oligodeoxynucleotide on proliferation and apoptosis
      of human melanoma A375 cell line].
AB  - AIM: To investigate effects of bcl-2 fully phosporothioated antisense
      oligodeoxynucleotide(bcl-2 ASODN) on proliferation and apoptosis of human
      melanoma A375 cell, and its possible mechanism. METHODS: Proliferation and
      apoptosis of A375 cell with bcl-2 ASODN treatment were evaluated by MTT
      colorimetric assay, laser scanning confocal microscope (LSCM), TUNEL and Annexin
      V/propidium iodide(PI), and the level of bcl-2 mRNA expression in A375 cell was
      detected by RT-PCR before and after being treated by bcl-2 ASODN. RESULTS: MTT
      assay demonstrated that bcl-2 ASODN could inhibit the proliferation of the cells
      in both time and concentration dependent manner. Characteristic morphologic
      apoptosis changes were observed by LSCM after incubated with bcl-2 ASODN for 48
      h. Most nucleus were labeled in brown by TUNEL in ASODN group, but not markedly
      labeled both in SODN and control group. The apoptosis rate of A375 cells in 30
      micromol/L bcl-2 ASODN group was significantly higher than that in bcl-2 SODN and
      in control group. The bcl-2 ASODN-induced apoptosis of A375 cells, which was
      accompanied by declined expression of bcl-2 mRNA was distinctly lower than that
      in SODN and control groups. CONCLUSION: These results suggest that bcl-1 ASODN
      can not only inhibit proliferation but also induce apoptosis of human melanoma
      A375 cells in vitro, and the apoptosis-induced mechanism is down-regulating
      expression of bcl-2 mRNA.

PMID- 16806010
TI  - [Effect of novel human chemokine-like factor superfamily 8 on proliferation and
      EGFR expression of tumor cells].
AB  - AIM: To investigate the effect of chemokine-like factor superfamily 8 (CKLFSF8)
      on proliferation and epidermal growth factor receptor (EGFR) expression of tumor
      cells. METHODS: Expression of CKLFSF8 mRNA in BGC823 and K562 cells was assayed
      by RT-PCR. Then target gene was transfected into tumor cells by lipid method, and
      cell growth was observed by inverted microscope. Cell proliferation was
      determined by MTT assay and expression of EGFR on tumor cells was determined by
      immunocytochemical technique. RESULTS: CKLFSF8 was expressed in the two tumor
      cells. After transfection, cell proliferation was inhibited (P<0.05) and the
      expression of EGFR of tumor cells was also discovered to be inhibited (P<0.05).
      CONCLUSION: The finding shows that cell proliferation and expression of EGFR of
      tumor cells can be inhibited by transfection of CKLFSF8. The new chemokine may
      has a bright prospect in the treatment of tumor.

PMID- 16806011
TI  - [Effect of IL-6 and TNF-alpha on Dengue virus infection of human dendritic
      cells].
AB  - AIM: To study the effect of IL-6 and TNF-alpha on Dengue virus (DV) infection of
      human dendritic cells (DCs). METHODS: Monocytes isolated from healthy human
      peripheral blood were incubated in medium with GM-CSF and IL-4 for 7-10 days, and
      then were collected and identified by transmission electron microscope,
      immunohistochemistry and lymphocytes stimulatory ability assay. DCs infected with
      DV type II (DV(2)) were incubated with IL-6, TNF-alpha at high, medium and low
      concentration. The supernatants were collected at 6 h, 24 h, 48 h, 72 h and 96 h.
      The virus titers were determined by plaque assay and the number of DCs at 48 h
      postinfection was mensurated by MTT. RESULTS: IL-6 at medium or low concentration
      increased DV(2) replication in DCs, whereas TNF-alpha at high and medium
      concentration inhibited DV(2) replication in DCs. Cytokines had no effect on the
      number of normal DCs. CONCLUSION: IL-6 and TNF-alpha may play an important role
      in the pathogenicity and immunity of Dengue virus.

PMID- 16806012
TI  - [Protection of human renal tubular epithelial cells (HK-2 cells) from hypoxia
      reoxygenation damage by recombinant adenovirus containing hCGPx gene].
AB  - AIM: To study the protective effect of human renal tubular epithelial cells (HK-2
      cells) from hypoxia-reoxygenation damage by transfection of recombinant
      adenovirus-mediated human cytosolic glutathione peroxidase(hCGPx) gene. METHODS:
      Recombinant pGEM-T vector containing hCGPx cDNA and pACCMV-pLpA adenovirus
      shuttle plasmid was constructed. Then the shuttle plasmid pACCMV-hCGPx and pJM17
      were co-transfected into 293 cells and recombinant adenovirus AdCMV-hCGPx was
      obtained. Cultured HK-2 cells were transfected with AdCMV-hCGPx or vacant
      recombinant adenovirus (control). The expression ratio of transfected hCGPx gene
      were studied. Cell viability, the percentage of apoptosis and death were
      evaluated after hypoxia-reoxygenation damage. RESULTS: The expression ratio of
      hCGPx gene was higher in the AdCMV-hCGPx transfected cells than that in the
      control group (P<0.01). After hypoxia-reoxygenation damage, the viability of
      hCGPx gene transfected cells was significantly higher than that of control and
      the percentage of apoptosis and death of hCGPx transfected cells was
      significantly lower than that of control. CONCLUSION: The transfection of hCGPx
      mediated by recombinant adenovirus could protect renal tubular epithelial cells
      from hypoxia-reoxygenation damage in vitro.

PMID- 16806013
TI  - [Detection of TCR Vbeta subfamily sjTRECs in normal peripheral blood and cord
      blood].
AB  - AIM: To detect the existence of sjTRECs in TCR 23 Vbeta subfamilies in normal
      peripheral blood and cord blood, and to evaluate the recent thymic emigrants of
      naive T cells of different TCRbeta subfamilies. METHODS: Different amounts of DNA
      from samples (4 cases of thymocytes, 10 cases of cord blood and 10 cases of
      normal PBMCs) were amplified to estimate the frequency of 23 TCR Vbeta-Dbeta
      sjTRECs by using semi-nest PCR. RESULTS: At the same cellular concentration, the
      most frequency of Vbeta-Dbeta1 sjTRECs was found in thymocytes, the second was in
      cord blood, and the lowest was in peripheral blood. At 2x10(5), 5x10(4) and
      1x10(4) cells level, sjTRECs of most Vbeta subfamilies could be detected in cord
      blood and peripheral blood, while sjTRECs of some Vbeta subfamilies could be
      detected at 1x10(3) cells level. The frequencies of Vbeta2-, Vbeta4-, Vbeta7-,
      Vbeta11- and Vbeta19-Dbeta1 sjTRECs and the number of detectable Vbeta
      subfamilies from normal PBMCs were obviously lower than those from cord blood.
      CONCLUSION: The technique of semi-quantitive PCR to detect sjTRECs in 23 Vbeta
      subfamilies was successfully established. Naive T cells from different Vbeta
      subfamilies could be detected with different frequency.

PMID- 16806014
TI  - [Knockdown of Hsp701A induces K562 cells apoptosis by RNA interference].
AB  - AIM: To investigate the apoptosis of K562 cells induced by RNA interference(RNAi)
      targeting Hsp701A. METHODS: Small interference RNA (siRNA) targeting Hsp701A was
      generated and its eukaryotic expression vectors was constructed and transected
      into K562 cells. Proliferation, apoptosis and cell cycle of the transected cells
      was respectively detected by MTT colorimetry and FCM. RESULTS: The eukaryotic
      expression vector of siRNA against Hsp701A was successfully constructed and
      transfected into K562 cells, which markedly decreased the expression of Hsp701A
      on both mRNA and protein level. K562 cells transfected with the vector exhibited
      slower proliferation, increased apoptosis and increased G(0)/G(1) arrest.
      CONCLUSION: The inhibition of Hsp701A gene by RNAi may provide a foundation for
      the development of novel therapeutic strategy for chronic granulocyte leukemia
      (CML).

PMID- 16806015
TI  - [STAT1 antisense oligonucleotides inhibit secretion of TNF-alpha, IL-8 and NO in
      alveolar macrophages of rats suffering from interstitial pulmonary fibrosis].
AB  - AIM: To investigate the effect of signal transducer and activator of
      transcription 1 (STAT1) antisense oligonucleotides (ASON) on secretion of TNF
      alpha, IL-8 and NO by alveolar macrophages (AMs) of rats with bleomycin (BLM)
      induced pulmonary fibrosis. METHODS: Five adult female Wistar rats were
      intratracheally instilled with BLM. After 7 days, the rats were sacrificed under
      ketamine anaesthesia and bronchoalveolar lavage (BAL) was performed to obtain
      AMs. AMs were divided into four groups: STAT1 ASON, STAT1 sense oligonucleotides
      (SON), dexamethasone (DEX) and control groups. Culture medium was collected at 36
      hours after adding STAT1 ASON, STAT1 SON and DEX, respectively. The
      concentrations of TNF-alpha, IL-8 and NO in the culture medium were detected.
      RESULTS: The concentrations of TNF-alpha, IL-8 and NO in STAT1 ASON group were
      lower than those in STAT1 SON, DEX and control groups (P<0.05). Moreover, the
      concentrations of TNF-alpha, IL-8 and NO in DEX group were also lower than those
      in control and STAT1 SON groups (P<0.05). But compared with control group, the
      concentrations of TNF-alpha, IL-8 and NO in STAT1 SON group was not significantly
      different (P<0.05). CONCLUSION: STAT1 ASON can inhibit the secretion of TNF
      alpha, IL-8 and NO in AMs. STAT1 may become a target for treating pulmonary
      fibrosis.

PMID- 16806016
TI  - [Biologic activity of bispecific single chain antibody against human gamma
      seminoprotein and CD3 molecule].
AB  - AIM: To construct a recombinant vector which expresses bispecific single chain
      antibody (BsscFv) against human gamma-seminoprotein and CD3 molecule and evaluate
      its biologic activity. METHODS: The BsscFv gene was constructed by the splicing
      overlap extensive (SOE) PCR and then a flexible peptide linker was inserted
      between anti-human gamma-seminoprotein single chain Fv gene and anti-CD3 single
      chain Fv gene. The fusion gene was subcloned into the pSectag2-B plasmid and was
      expressed in HeLa cell lines. After being analyzed by SDS-PAGE and Western blot,
      the expressed product was purified through a Ni(2+)-NTA superflow affinity
      chromatography column. Flow cytometry (FCM) was used to detect the binding
      activity of BsscFv to CD3(+) cell line Jurkat cells and prostate carcinoma cells
      LNCaP. In vitro killing effect on target cells (LNCaP) mediated by BsscFv was
      determined by chromium(51)-release test. The effect of CTLs mediated by BsscFv on
      inhibiting tumor growth was observed by utilizing nude mice bearing prostate
      cancer cells. RESULTS: DNA sequencing indicated that BsscFv gene consisted of
      1,500 bp, encoding 500 amino acids. SDS-PAGE and Western blot analysis showed
      that the expressed product with relative molecular mass of 61,000 existed in
      culture supernatant of Hela cells. Flow cytometry analysis demonstrated that the
      binding rate of BsscFv to LNCaP cells and Jurkat cells was 54.1% and 53.7%,
      respectively. In vitro, BsscFv mediated cytotoxicity of CTLs to LNCaP cells as
      confirmed by chromium(51)-release assay. In prostate cancer nude mouse model,
      BsscFv inhibited tumor's growth as compared with control group. CONCLUSION: The
      BsscFv against human gamma-seminoprotein and CD3 molecule possesses certain
      biologic activity, and in vitro and in vivo it can mediate cytotoxicity of CTLs
      to prostate cancer cells.

PMID- 16806017
TI  - [Optimized expression of a single-chain Fv antibody against human
      asialoglycoprotein receptor and determination of its affinity constant].
AB  - AIM: To express and purify a single chain Fv antibody (scFv) C1 against human
      hepatic asialoglycoprotein receptor (ASGPR) and to determine affinity constant of
      the purified scFv C1. METHODS: The specific anti-ASGPR phage clone C1 was
      transfected into E. coli HB2151. The single colony was chosen to be inoculated
      into 2 x TY medium and shaken (250 r/min) overnight at 37 degrees C. After 1 in
      100 dilution in 2 x TY medium and induced for secreted expression, scFv C1 was
      induced at different concentrations (0.25, 0.5 and 1.0 mmol/L IPTG) overnight at
      37 degrees C, 25 degrees C and 20 degrees C, respectively. The supernatant was
      precipitated with saturated ammonium sulfate and its sediment was analyzed by SDS
      PAGE. In addition, the sediment was resuspended in 30 mL PBS and dialyzed against
      PBS overnight at 4 degrees C. The expressed scFv C1 was purified by Ni(2+)
      chelating HiTrap HP column and the purity of the purified scFv C1 was identified
      by SDS-PAGE. Then affinity constant of scFv C1 was determined by noncompetitive
      enzyme immunoassay. RESULTS: After induced with 0.5 mmol/L IPTG overnight at 25
      degrees C, the amount of expressed scFv C1 increased greatly and its relative
      molecular mass was about 28,000, and it existed in culture supernant in soluble
      form. The purity of scFv C1 by nickel-agarose column was above 95% and its yield
      was about 0.8 mg/L. The affinity constant of the purified scFv C1 was confirmed
      to be (2.31+/-0.36)x10(-7) mol/L. CONCLUSION: The E. coli HB2151 infected with
      phage C1 clones may express soluble scFv C1 with low affinity, which has
      potential applications to gene therapy of hepatocellular carcinoma.

PMID- 16806018
TI  - [Construction and expression of a fusion protein of scFv against human
      acetylcholine receptor-human serum albumin in E. coli].
AB  - AIM: To prepare the fusion protein of a single chain variable fragment 637
      (scFv637) against human acetylcholine receptor (AChR) and human serum albumin
      (HSA) to increase the stability of scFv637. METHODS: HSA gene was amplified by
      PCR and cloned into vector pHEN2 containing a scFv637 gene to construct
      recombinant vector pHEN2-scFv637-HSA and then transformed into E. coli HB2151 for
      expression. The expression of fusion protein in periplasm of E. coli was detected
      by dot hybridization. Relative molecular mass of fusion protein was checked by
      SDS-PAGE and Western blot. RESULTS: Agarose gel electrophoresis analysis showed
      that the size of HSA gene and fusion gene was about 1,770 bp and 7,054 bp,
      respectively. DNA sequencing proved that the nucleotide sequence of constructed
      scFv637-HSA gene was correct and it was cloned into the open reading frame (ORF)
      of pHEN2. scFv637-HSA fusion protein only existed in periplasm of E. coli HB2151
      transformed with pHEN2-scFv637-HSA. SDS-PAGE and Western blot analysis indicated
      that relative molecular mass of fusion protein was about 95,900. CONCLUSION: The
      scFv637-HSA fusion protein can be successfully expressed in E. coli HB2151, which
      provides a sound basis for further research into its function and clinical
      application.

PMID- 16806019
TI  - [Preparation and characterization of monoclonal antibodies against chicken
      interferon-gamma].
AB  - AIM: To prepare monoclonal antibodies (mAb) against chicken interferon-gamma
      (ChIFN-gamma). METHODS: By using lymphocyte hybridoma technique, the inclusion
      body of the recombined bacteria, BL21(DE3) (pET-ChIFN-gamma), was harvested and
      used to immunize BALB/c mice. With the purified GST-ChIFN-gamma as detecting
      antigen, mAbs against ChIFN-gamma were prepared, and positive hybridoma clones
      were screened by indirect ELISA. The specificity of the mAb was characterized by
      indirect ELISA, Dot-ELISA and Western blot. RESULTS: Two hybridoma cell lines
      secreting mAbs against ChIFN-gamma named 1G5, 5E3 were obtained. The
      immunoglobulin subclasses of both 2 mAbs were IgG2a, and the ELISA titers of 2
      mAbs ascitic fluids were 1:160,000, 1:12,000 respectively. In Dot-ELISA test, the
      2 mAbs could only react with BL21 (DE3) (pET-ChIFN-gamma), BL21 (pGEX-6P-1-ChIFN
      gamma), which expressed His-ChIFN-gamma, GST-ChIFN-gamma, respectively. Western
      blot analysis confirmed that the 2 mAbs could only react with GST-ChIFN-gamma and
      His-ChIFN-gamma proteins. CONCLUSION: Two mAbs specific to the protein of chicken
      interferon gamma are obtained, which may have important application value in
      further studies on immune detection, the functions of immune cells and immune
      regulation.

PMID- 16806020
TI  - [Preparation and characterization of monoclonal antibody against DR5].
AB  - AIM: To prepare monoclonal antibodies(mAb) against DR5 and characterize their
      properties. METHODS: BALB/c mice were immunized with DR5, and then mAb was
      prepared by hybridoma technique. Ig subclass and specificity of mAbs was analyzed
      by ELISA and flow cytometry, respectively. The titres of mAbs in ascitic fluid,
      relative affinity and epitopes recognized by mAbs were determined by indirect
      ELISA. RESULTS: Four hybridoma cell lines secreting anti DR5 mAbs were obtained.
      Their Ig subclass belonged to IgG1. The titers of 4 mAbs in ascitic fluid were
      1x10(-4) - 5x10(-6). Affinity constant of mAbs were 1x10(9). They recognized 2
      different epitopes on DR5 molecule. CONCLUSION: Four mAbs against DR5 are
      prepared successfully, which provides useful reagent for clinical diagnosis and
      further research.

PMID- 16806021
TI  - [Preparation and characterization of monoclonal antibody against human LSECtin].
AB  - AIM: To prepare and characterize monoclonal antibody (mAb) against human LSECtin
      (liver and lymph node sinusoidal endothelial cell C-type lectin) protein.
      METHODS: BALB/c mice were immunized with prokaryotically expressed human LSECtin
      protein. The splenocytes from the immunized mice were fused with murine myeloma
      cells (Sp2/0) and then the mAb-positive hybridoma cells were screened by indirect
      ELISA. Reaction of mAb to LSECtin antigen was characterized by Western blot,
      indirect immunofluorescent staining, immunohistochemical staining and FCM.
      RESULTS: Eight hybridoma cells secreting mAbs were established. The isotypes of
      the mAbs were IgG. Ascites titers were between 1:10(6) - 1:10(7). All the mAbs
      recognized human LSECtin protein on LSECtin-transfected 3T3 cells and six of the
      mAbs specifically recognized liver sinusoidal endothelial cells. CONCLUSION:
      Eight anti-LSECtin mAbs have been obtained. The characterization of the mAbs
      indicate that they show fine specificity by Western blot, indirect
      immunofluorescent staining, immunohistochemical staining and FCM, which can
      provide a powerful reagent for the functional study of LSECtin.

PMID- 16806022
TI  - [Preparation and identification of the rabbit antibody against human sialin].
AB  - AIM: To prepare the rabbit antibody against human sialin and identify its
      properties. METHODS: Recombinant expression vector pGEX-5X-1-sialin was
      constructed, in which the sialin cDNA encoding the 1-38 aa was fused to the C
      terminal of the gene encoding the GST protein. The GST-sialin (N1-38) fusion
      protein was expressed in E. coli JM109 at 37 degrees C in the presence of IPTG at
      0.1 mmol/L for induction for 3 hours, purified by GSTrap FF, and then used as the
      immunogen to prepare the rabbit polyclonal antibody. The properties of antiserum
      against human sialin were identified by ELISA, Western blot and
      immunocytochemistry. RESULTS: The recombinant expression plasmid pGEX-5X-1-sialin
      was constructed. The GST-sialin (N1-38) fusion protein was highly expressed with
      a molecular weight of 30 kDa, and the yield of the fusion protein was about 20%
      to 30% in total E. coli protein. The titre of antiserum against human sialin was
      1:32,000. Western blot analysis proved the rabbit polyclonal antibody could
      identify both GST-sialin (N1-38) fusion protein and GST. Besides, it specially
      recognized a 55 kDa band expressed in the human submandibular gland (HSG) cell
      line. The antigen recognized by the antibody was located in the cytoplasm and
      nucleus of HSG cell. CONCLUSION: The successful preparation of the polyclonal
      antibody against human sialin will provide efficient affinity reagent for further
      functional study of sialin expressed in human salivary glands.

PMID- 16806023
TI  - [Inhibition of rhodiola on the growth of EVC-304 cell line].
AB  - AIM: To observe the effect of rhodiola on human umbilical vein endothelial cell
      line EVC-304. METHODS: EVC-304 was cultured and divided into two groups: control
      group and rhodiola-treated group. Three days after treatment, cell survival rate
      drug concentration curve was obtained by counting the survival cells, and cells
      in each group were stained by Wright's stain and observed under microscope. Cell
      cycle was determined by flow cytometry (FCM). RESULTS: The survival cells in
      rhodiola-treated group was much less than those in control group. More cells in
      rhodiola-treated group stayed in G(1) phase while less in S phase when compared
      with those in control group by FCM. CONCLUSION: Rhodiola can inhibit the growth
      of human endothelial cell line EVC-304, perhaps through inhibiting the
      proliferation of the cells. This may lay the foundation for the mechanism study
      and clinical application of rhodiola in prevention of pulmonary artery
      hypertension.

PMID- 16806024
TI  - [Immunopotentiation of novel adjuvant SWZY on the poorly immunogenic murine
      melanoma vaccine].
AB  - AIM: To evaluate the immunopotentiation of novel adjuvant SWZY on the cancer
      vaccine of poorly immunogenic melanoma. METHODS: C57BL/6 mice immunized with
      inactivated D5 melanoma cells were divided into 6 groups: the control without
      adjuvants, with FCA, FCA+IL-2+GM-CSF, FIA+IL-2+GM-CSF, FIA+SWZY, and FIA+SWZY+IL
      2+GM-CSF. Three days after completion of immunization, DTH response, specific
      killing activity of splenocytes and the level of IFN-gamma and IL-10 in serum and
      splenocytes' culture supernatant were assayed in half of the mice in each group.
      The rest were subject to live D5 tumor cell challenge. Three weeks after tumor
      inoculation, the same immunological parameters were measured. RESULTS: DTH
      response, splenocytes' killing activity of all the experimental groups were
      markedly higher than those in the control group (P<0.05), but decreased as the
      tumor grew larger. The level of IFN-gamma in serum or splenocyte culture
      supernatant of each experimental group was significantly higher than that of the
      control (P<0.05) before tumor formation, whereas IL-10 level was lower than that
      of the control (P<0.05). After tumor formation, the level of IFN-gamma in all
      groups decreased while that of IL-10 increased in general, but the levels of IFN
      gamma and IL-10 in group FCA and FIA+SWZY didn't change very much. CONCLUSION:
      All kinds of adjuvants can enhance the cell-mediated immune response against
      poorly immunogenic tumor to some extent. The novel adjuvant SWZY can strengthen
      immunoresponses similar to FCA. With few harmful side-effect, SWZY might be a
      promising adjuvant for cancer vaccine.

PMID- 16806025
TI  - [Expression and purification of human MT-2a fusion protein in prokaryotic cells
      and preparation of its antiserum].
AB  - AIM: To express and purify human MT-2a in prokaryotic cells and to prepare the MT
      2a-specific rabbit antiserum. METHODS: GST-MT-2a fusion protein was expressed
      after IPTG induction and further purified with Glutathione Sepharose 4B. Then the
      purified GST-MT-2a fusion protein was used to immunize New Zealand rabbits. The
      titer and specificity of rabbit antiserum were evaluated by double
      immunodiffusion, ELISA and Western blot. RESULTS: GST-MT-2a fusion protein was
      highly expressed. The final yield of the pure GST-MT-2a was about 38 mg per liter
      of bacterial culture. Its antiserum with high specificity and potency was also
      obtained. CONCLUSION: The successful expression of GST-MT-2a fusion protein in E.
      coli and the preparation of MT-2a specific rabbit antiserum will be valuable for
      the study on the function of human MT-2a.

PMID- 16806026
TI  - Socioeconomic differences and motorcycle injuries: age at risk and injury
      severity among young drivers. A Swedish nationwide cohort study.
AB  - STUDY OBJECTIVE: The study examines whether there are socioeconomic differences
      among young motorcycle drivers (aged 16-25) involved in road-traffic injuries
      with regard to age and injury severity. DESIGN: Nationwide retrospective register
      based cohort study. SETTING AND PARTICIPANTS: Subjects born in 1970-1972 were
      extracted from the Swedish Population and Housing Census of 1985 (n = 334,070).
      Individual records from the 1985 census were linked to police-reported data and
      hospital-based data for the period 1988-1995 on the basis of a search for each
      subject's first registered road-traffic injury as a motorcycle driver (n = 2034).
      Information on household socioeconomic group was taken from the Swedish census of
      1985. Two categories of crash severity were analysed (minor injury and
      severe/fatal injury), based on assessments of the police and according to length
      of hospitalization. MAIN RESULTS: Incidence of motorcycle injury varies
      considerably according to age of driver, reaching a peak at the age of 17. The
      greatest differences in injury risk between socioeconomic groups are present when
      their members are aged 17-19. At the age of 18, subjects belonging to low
      socioeconomic positions run a risk of injury occurrence 2.5 times higher than
      those belonging to the highest socioeconomic category. Young drivers in lower
      socioeconomic groups have higher odds for both minor and severe injuries than
      their counterparts in the highest socioeconomic group, but there is no further
      increase for the latter. CONCLUSIONS: The study demonstrates how crucial the
      first years of driving are in relation to injury, and how wide the gap is in
      terms of socioeconomic differences at these ages, suggesting that this is the
      most appropriate time for intervention.

PMID- 16806027
TI  - Braking hazards of golf cars and low speed vehicles.
AB  - Research and analysis of braking issues for golf cars and other low speed
      vehicles (LSVs) are reported in this study. It is shown that many such vehicles
      only provide braking for their rear wheels, which can lead to a driver losing
      control during travel on typical steep downgrades. The braking performance of a
      golf car equipped with brakes on two or four wheels was analyzed to determine the
      effects of two and four wheel brake designs on braking efficiency and vehicle yaw
      stability. Besides reducing braking efficiency, it is demonstrated that
      installing brakes on only the rear wheels can lead to directional instability
      (fishtailing) and rollover when the rear wheels are braked until skidding occurs.
      The nonexistence of golf course standards and the inadequacy of golf car and LSV
      standards are noted and a connection between this and the comparatively high
      level of accidents with such vehicles is inferred. Based on these results, it is
      advisable to install brakes on all four wheels of golf cars and LSVs. In
      addition, new safety standards should be considered to reduce the occurrence of
      golf car accidents on steep downhill slopes.

PMID- 16806028
TI  - The development of a naturalistic data collection system to perform critical
      incident analysis: an investigation of safety and fatigue issues in long-haul
      trucking.
AB  - Traditionally, both epidemiological and empirical methods have been used to
      assess driving safety. This paper describes an alternative, hybrid, naturalistic
      approach to data collection that shares advantages with each traditional
      approach. Though this naturalistic approach draws on elements of several safety
      techniques that have been developed in the past, including the Hazard Analysis
      Technique, instrumented vehicle studies, and fleet studies of driving safety
      interventions, it has a number of unique elements. Sophisticated instrumented
      vehicles collected over 400,000 km of commercial vehicle data to address the long
      haul trucking application described in this paper. The development of this data
      collection and analysis method and data collection instrumentation has resulted
      in a set of valuable tools to advance the current state-of-the-practice in
      driving safety assessment. An application of this unique approach to a study of
      long-haul truck driver performance, behavior, and fatigue is described herein.

PMID- 16806029
TI  - Cryopreservation of Trypanosoma brucei gambiense in a commercial cryomedium
      developed for bull semen.
AB  - There have been major advances in the formulation of cryomedia for spermatozoa
      owing to their economic importance. In this study, the suitability of the
      commercial cryomedium Triladyl developed for bull semen was evaluated for the
      cryopreservation of Trypanosoma brucei gambiense. Cryopreservation efficacy was
      determined by direct counting of motile trypanosomes and by viability assessment
      using in vitro and in vivo methods. Culture medium containing 10% glycerol was
      used as the control. Trypanosomes cryopreserved in Triladyl demonstrated a higher
      in vitro viability than those in culture medium with 10% glycerol. Similar
      results were obtained in vivo in immunosuppressed Mastomys natalensis.
      Trypanosomes cryopreserved in Triladyl showed better growth characteristics than
      those in culture medium with glycerol. It can be concluded that the use of
      Triladyl in the cryopreservation of T. b. gambiense leads to a better survival of
      the trypanosomes which could lead to an improved isolation of T. b. gambiense
      from sleeping sickness patients.

PMID- 16806030
TI  - Extended DLVO theory: electrostatic and non-electrostatic forces in oxide
      suspensions.
AB  - According to classical DLVO theory all ions of background salt solution with the
      same ionic charge should result in the same effective force between colloidal
      particles. However, the relative effectiveness of different ions in influencing
      forces between ceramic oxide surfaces follows either a reversed Hofmeister
      sequence or a direct Hofmeister sequence depending on the type of oxide and if
      the pH is above or below the isoelectric point (iep). This ion specificity is
      inexplicable in classical double layer theory that deals only with pure
      electrostatic forces acting between the ions and the colloidal particles. A
      theoretical explanation is given here. At, and above, biological salt
      concentrations other, non-electrostatic (NES) ion specific forces act that are
      ignored in such modeling. In this overview we present the basic theory for the
      double layer near a single oxide surface and for the extended DLVO forces between
      oxide colloidal particles that accounts for these NES forces. We will demonstrate
      that ion specificity can be understood to a large degree once NES forces are
      included consistently in the non-linear theory.

PMID- 16806031
TI  - Application of emulsifiers/stabilizers in dairy products of high rheology.
AB  - The role played by low molecular weight emulsifiers (mono- and di-glycerides) and
      non-dairy stabilizers (alginates, carrageenans, gums and gelatins) in the
      formation and stabilization of liquid milk (and specifically a functionalized
      milk containing omega-3), yoghurt and ice cream has been reviewed. Attention is
      given to the interactions that may occur between the reactive sites on
      polysaccharide stabilizers and milk proteins and other milk components, and to
      the desirable characteristics, e.g., viscosity/consistency, appearance and
      mouthfeel, body and texture, imparted to yoghurt and ice cream by addition of
      emulsifiers and gums.

PMID- 16806032
TI  - Importance of head group polarity in controlling aggregation properties of
      cationic gemini surfactants.
AB  - Cationic gemini surfactants have been extensively studied in the recent past and
      the effect of chain length, spacer length and nature on aggregation behavior has
      been examined. But the effect of variation in head group polarity on
      micellization has not been examined. Hence, the effect of head group polarity of
      the butane-1,4-bis(dodecyldimethylammonium bromide) surfactants on aggregation
      properties is studied through conductance, surface tension, viscosity, and small
      angle neutron scattering (SANS) measurements. The critical micellar concentration
      (cmc), average degree of micelle ionization (beta(ave)), minimum area per
      molecule of surfactant at air-water interface (A(min)), surface excess
      concentration (Gamma(max)) and Gibbs free energy change of micellization (DeltaG
      degrees (mic)) of the surfactants were determined from conductance and surface
      tension data. The aggregation numbers (N), dimension of micelle (b/a), effective
      fractional charge per monomer (alpha) were determined from SANS and hydration of
      micelle (h(m)) from viscosity data. The increasing head group polarity of gemini
      surfactant having spacer chain length of 4 methylene units promotes micellar
      growth, leading to decrease in cmc, beta(ave), DeltaG degrees (mic) and increase
      in N and b/a. This is well supported by the observed increase in hydration (h(m))
      of micelle with increase in aggregation number (N) and dimension (b/a) of
      micelle. The Kraft temperature (k(T)), foamability and foam stability as a
      function of head group polarity of gemini surfactants were also examined.

PMID- 16806033
TI  - Water-in-diesel emulsions and related systems.
AB  - Water-in-diesel emulsions are fuels for regular diesel engines. The advantages of
      an emulsion fuel are reductions in the emissions of nitrogen oxides and
      particulate matters, which are both health hazardous, and reduction in fuel
      consumption due to better burning efficiency. An important aspect is that diesel
      emulsions can be used without engine modifications. This review presents the
      influence of water on the emissions and on the combustion efficiency. Whereas
      there is a decrease in emissions of nitrogen oxides and particulate matters,
      there is an increase in the emissions of hydrocarbons and carbon monoxide with
      increasing water content of the emulsion. The combustion efficiency is improved
      when water is emulsified with diesel. This is a consequence of the
      microexplosions, which facilitate atomization of the fuel. The review also covers
      related fuels, such as diesel-in-water-in-diesel emulsions, i.e., double
      emulsions, water-in-diesel microemulsions, and water-in-vegetable oil emulsions,
      i.e., biodiesel emulsions. A brief overview of other types of alternative fuels
      is also included.

PMID- 16806034
TI  - Megakaryocyte cell sorting from diosgenin-differentiated human erythroleukemia
      cells by sedimentation field-flow fractionation.
AB  - Anticancer differentiation therapy could be one strategy to stop cancer cell
      proliferation. Human erythroleukemia (HEL) cell line, incubated with 10 microM
      diosgenin, underwent megakaryocytic differentiation. Thus, the association
      diosgenin/HEL could be used as a model of chemically induced cellular
      differentiation and anticancer treatment. The goal of this work was to determine
      the capacity of sedimentation field-flow fractionation (SdFFF) to sort
      megakaryocytic differentiated cells. SdFFF cell sorting was associated with
      cellular characterization methods to calibrate specific elution profiles. As
      demonstrated by cell size measurement methods, cellular morphology, ploidy, and
      phenotype, we obtained an enriched, sterile, viable, and functional fraction of
      megakaryocytic cells. Thus, SdFFF is proposed as a routine method to prepare
      differentiated cells that will be further used to better understand the
      megakaryocytic differentiation process.

PMID- 16806035
TI  - [Abecedary of the "Annales". Part 14].
AB  - The terms included and detailed in the present part are: Median, Medline, MeSH,
      meta-analysis, fixed effects model, random effects model, Mean.

PMID- 16806036
TI  - [Posthysterectomy posterior compartment prolapse: Preliminary results of a novel
      transvaginal surgical procedure using polypropylene mesh via the low
      transobturator route].
AB  - OBJECTIVE: The aim of this study is the description and anatomical and functional
      outcome assessment of a novel surgical procedure, based on rectovaginal fascia
      defect repair with polypropylene mesh using the tension-free transobturator and
      infracoccygeal route based on the integral theory developed by Petros. MATERIALS
      AND METHOD: Prospective, consecutive and single centre study performed between
      February 2003 and April 2005. Inclusion criteria were symptomatic
      posthysterectomy stage three to four regarding posterior compartment prolapse
      according to the Baden and Walker classification, with no anterior and/or apical
      prolapse. Principles and description of this new surgical procedure are
      described. RESULTS: Fourteen patients, with a mean age of 63.5 years and a mean
      body mass index of 29.2, were included in the study. All the patients had
      previous hysterectomy, 64.3% reported at least one previous surgery for pelvic
      organ prolapse, 44.5% reported at least one reoperation. All patients complained
      of rectocele and/or enterocele stage three. No perioperative or postoperative
      complication occurred. With a median follow-up of 13 months (range 3-32.9), no
      recurrence and no anterior or apical compartment prolapse occurred. No vaginal
      erosion an infection of the mesh was observed. The mean level of subjective
      satisfaction was 9.23 on a visual analogical scale (0-very disappointed, 10-very
      satisfied). CONCLUSION: This new surgical procedure is effective and safe for the
      repair of posthysterectomy large posterior compartment prolapse. A long-term
      follow-up is required to confirm these promising results.

PMID- 16806037
TI  - [Prognostic factors after surgical resection for hilar cholangiocarcinoma].
AB  - AIMS: To evaluate short and long-term results in 23 patients resected for hilar
      cholangiocarcinoma. METHODS: Between January 2001 and December 2003, 23 patients
      with hilar cholangiocarcinoma were resected and considered for retrospective
      analysis. Univariate and multivariate analysis were performed on several
      clinicopathological variables in order to evaluate the short-term results. Median
      follow-up was 11 months (interquartile range 2-20 months). RESULTS: A major liver
      resection was performed in 19 out of 23 patients (82%): a right hepatectomy
      extended to segment 4 in 5 patients and a left hepatectomy in 14 patients.
      Resection of the caudate lobe was performed in 7 patients (30%). No hospital
      mortality occurred. Overall morbidity rate was 43%. The 1-year survival rate was
      63.2% with a median survival of 19 months. Tumor recurrence appeared in 12
      patients (52%). Low preoperative albumin level (P=0.006), presence of positive
      resection margin (P=0.03) and T-stage (P=0.02) were found to be related to a
      worse median survival. On multivariate analysis, only the preoperative albumin
      level and the presence of positive margin were confirmed as independent
      prognostic factors. CONCLUSION: Aggressive surgical approach remains the only
      potentially curative therapy for the hilar cholangiocarcinoma. Low preoperative
      albumin level, presence of positive resection margin and T-stage resulted as
      factors influencing the prognosis after resection.

PMID- 16806038
TI  - [Princeps procedure of gastric bypass for morbid obesity].
AB  - Technical variants of gastric bypass for morbid obesity are briefly described in
      this article including the three main steps: Roux-en-Y intestinal loop, gastric
      pouch and gastrojejunal anstomosis.

PMID- 16806039
TI  - [Abecedary of the "Annales". Part 15].
AB  - The terms included and detailed in the present part are: number needed to treat,
      number needed to harm, clinical relevance, PICO.

PMID- 16806040
TI  - The use of a heel-mounted accelerometer as an adjunct measure of slip distance.
AB  - A human-centered measure of floor slipperiness could be useful as an adjunct to
      conventional tribologic measures. This paper reports on the development and
      evaluation of a measure of slip distance based on variables derived from the
      signal of a heel-mounted accelerometer. Twenty-one participants walked on a
      laboratory runway under several surface slipperiness conditions at three walking
      speeds during a protocol designed to produce a wide range of slip distances at
      heel strike. Analysis of variance showed significant effects of slip distance (no
      slip, micro-slip and slide), walking speed (1.52, 1.78 and 2.13 m/s) and their
      interactions on peak forward acceleration, peak vertical acceleration and
      deceleration time of the heel following heel strike in 704 trials. Regression
      analysis of slip distance and deceleration time showed the strongest relationship
      with R2=0.511. Large individual variation in the strength of this relationship
      was observed. The heel-mounted accelerometer may have utility as an adjunct
      measure in the evaluation of floor slipperiness, particularly for field
      applications where direct measurement may not be feasible.

PMID- 16806041
TI  - The effects of glove thickness and work load on female hand performance and
      fatigue during a infrequent high-intensity gripping task.
AB  - In various workplaces, gloves are commonly employed to protect the hands with the
      design rationale of 'the thicker the gloves, the better the protection'.
      Therefore, the present paper investigated the effects of glove thickness on hand
      performance and fatigue during two infrequent high-intensity gripping tasks, such
      as 5-s and sustained tasks. The hand performance was evaluated by maximum
      volitional contraction (MVC) and its associated time needed to reach the MVC
      (TMVC), and the total force generation (TFG) during the sustained task. The hand
      fatigue was assessed by MVC degeneration (DeltaMVC), the shift in time needed to
      reach the MVC (DeltaTMVC), and the maximal endurance time (MET) associated with
      the sustained task. Ten female subjects took part in the experiment voluntarily.
      The four-gloved conditions included bare hand, wearing one layer (Cotton-1),
      wearing two layers of cotton gloves (Cotton-2), and covering the handle with two
      layers of cotton glove and exerting with the bare hand (Covered-2). The results
      indicates that wearing gloves decreased the grip MVC, and the thicker the gloves,
      the less the grip MVC, but the wearing style did not change the MVC (Cotton-2 MVC
      was indifferent from Covered-2 MVC). As to muscular fatigue, on the other hand,
      wearing gloves did not affect DeltaMVC, MET, TMVC, or DeltaTMVC. Due to the
      greater bare-hand MVC and indifferent MET, bare-hand TFG was better than those
      conditions with gloves. Finally, the load specified here did not alter TMVC or
      DeltaTMVC, but the greater the load, the more strength degeneration (DeltaMVC)
      was induced.

PMID- 16806042
TI  - The effect of six keyboard designs on wrist and forearm postures.
AB  - There is increasing evidence that alternative geometry keyboards may prevent or
      reduce arm pain or disorders, and presumably the mechanism is by reducing awkward
      arm postures. However, the effect of alternative keyboards, especially the new
      designs, on wrist and arm postures are not well known. In this laboratory study,
      the wrist and forearm postures of 100 subjects were measured with a motion
      analysis system while they typed on 6 different keyboard configurations. There
      were significant differences in wrist extension, ulnar deviation, and forearm
      pronation between keyboards. When considering all 6 wrists and forearm postures
      together, the keyboard with an opening angle of 12 degrees , a gable angle of 14
      degrees , and a slope of 0 degrees appears to provide the most neutral posture
      among the keyboards tested. Subjects most preferred this keyboard or a similar
      keyboard with a gable angle of 8 degrees and they least preferred the keyboard on
      a conventional laptop computer. These findings may assist in recommendations
      regarding the selection of keyboards for computer usage.

PMID- 16806043
TI  - Spectroscopic and thermodynamic measurements of nucleotide-induced changes in the
      human 70-kDa heat shock cognate protein.
AB  - Hsp70 alternates between an ATP-bound state in which the affinity for substrate
      is low and an ADP-bound state in which the affinity for substrate is high, as a
      result Hsp70 assists the protein folding process through nucleotide-controlled
      cycles of substrate binding and release. In this work, we describe the cloning
      and purification of the human 70-kDa heat shock cognate protein, Hsc70, and the
      use of circular dichroism, intrinsic emission fluorescence, and isothermal
      titration calorimetry to characterize conformational changes induced by ADP and
      ATP binding. Binding of either ADP or ATP were not accompanied by a net change in
      secondary structure suggesting that the conformational rearrangement caused by
      nucleotide binding is localized. MgADP or MgATP had a greater effect in the
      stability at stress temperatures than ADP or ATP did. Isothermal titration
      calorimetry data pointed out that Hsc70 had a lower affinity for ATP (KD=710 nM)
      than for ADP (KD=260 nM).

PMID- 16806044
TI  - Signaling through MAP kinase networks in plants.
AB  - Protein phosphorylation is the most important mechanism for controlling many
      fundamental cellular processes in all living organisms including plants. A
      specific class of serine/threonine protein kinases, the mitogen-activated protein
      kinases (MAP kinases) play a central role in the transduction of various extra-
      and intracellular signals and are conserved throughout eukaryotes. These
      generally function via a cascade of networks, where MAP kinase (MAPK) is
      phosphorylated and activated by MAPK kinase (MAPKK), which itself is activated by
      MAPKK kinase (MAPKKK). Signaling through MAP kinase cascade can lead to cellular
      responses including cell division, differentiation as well as response to various
      stresses. In plants, MAP kinases are represented by multigene families and are
      organized into a complex network for efficient transmission of specific stimuli.
      Putative plant MAP kinase cascades have been postulated based on experimental
      analysis of in vitro interactions between specific MAP kinase components. These
      cascades have been tested in planta following expression of epitope-tagged
      kinases in protoplasts. It is known that signaling for cell division and stress
      responses in plants are mediated through MAP kinases and even auxin, ABA and
      possibly ethylene and cytokinin also utilize a MAP kinase pathway. Most of the
      biotic (pathogens and pathogen-derived elicitors) including wounding and abiotic
      stresses (salinity, cold, drought, and oxidative) can induce defense responses in
      plants through MAP kinase pathways. In this article we have covered the
      historical background, biochemical assay, activation/inactivation, and targets of
      MAP kinases with emphasis on plant MAP kinases and the responses regulated by
      them. The cross-talk between plant MAP kinases is also discussed to bring out the
      complexity within this three-component module.

PMID- 16806045
TI  - Vasoactive intestinal polypeptide (VIP) and VPAC1 receptor in adult human dental
      pulp in relation to caries.
AB  - OBJECTIVE: To quantitatively measure VIP levels and to qualitatively study the
      distribution of VIP fibres and demonstrate the presence of the VPAC1 receptor in
      human dental pulp from carious and non-carious adult human teeth. DESIGN: Dental
      pulp samples were collected from non-carious, moderately carious and grossly
      carious adult human teeth. VIP levels were determined using radioimmunoassay. The
      distribution of VIP fibres was studied using immunohistochemistry. The VPAC1
      receptor protein expression was determined by Western blotting. RESULTS: VIP
      levels were found to be significantly elevated in the dental pulp of moderately
      carious compared with non-carious (p=0.0032) or grossly carious teeth (p=0.0029).
      The distribution of VIP fibres was similar in non-carious and carious teeth,
      except that nerve bundles appeared thicker in the pulp samples from carious
      compared with non-carious teeth. Western blotting indicated that the VPAC1
      receptor proteins were detected in similar levels in pooled dental pulp samples
      from both carious and non-carious teeth. CONCLUSION: It is concluded that
      quantitative changes in the levels of VIP in human dental pulp during the caries
      process and the expression of VPAC1 receptor proteins in membrane extracts from
      carious and non-carious teeth suggests a role for VIP in modulating pulpal health
      and disease.

PMID- 16806046
TI  - Cytokine-induced nitric-oxide-dependent apoptosis in mouse osteoblastic cells:
      involvement of p38MAP kinase.
AB  - The apoptotic signalling induced by pro-inflammatory cytokines was examined in
      mouse osteoblastic MC3T3-E1 cells. Annexin-V/propidium iodine double-staining
      analysis demonstrated that the combination of tumour necrosis factor-alpha,
      interleukin-1beta and interferon-gamma caused cell death in osteoblastic cells
      mediated by apoptosis, not necrosis. Treatment with these cytokines resulted in
      potent enhancement of inducible nitric-oxide synthase (iNOS) mRNA and nitric
      oxide (NO) in the cells. A specific inhibitor of p38 mitogen-activated protein
      (MAP) kinase, i.e. SB203580, dose dependently inhibited the induction of iNOS
      mRNA, its enzyme product, NO and DNA fragmentation (as an apoptosis index) in the
      cytokine-treated cells (P<0.05). In contrast, PD98059, a specific inhibitor of
      MEK that acts immediately upstream of classic MAP kinase, had no effect on the
      induction of iNOS, NO or DNA fragmentation in the cells. These results
      demonstrate that this cytokine-induced apoptosis in mouse osteoblastic cells was
      mediated by a p38MAP-kinase-dependent iNOS system.

PMID- 16806047
TI  - Antimicrobial actions of benzimidazoles against the oral anaerobes Fusobacterium
      nucleatum and Prevotella intermedia.
AB  - BACKGROUND/OBJECTIVE: Benzimidazoles are widely used as proton-pump inhibitors to
      control stomach hyperacidity and have been found also to have antimicrobial
      actions against Helicobacter pylori and oral streptococci. Our primary aim was to
      determine if they are active also against oral anaerobes associated with
      gingivitis. Our major focus was on catabolism because it leads to production of
      inflammatory metabolites such as butyrate and ammonia. The benzimidazoles are
      effective in the protonated form at acid pH values and cause irreversible
      inhibition of enzymes associated with formation of drug-target disulfide bonds.
      METHODS: Fusobacterium nucleatum ATCC 25586 and Prevotella intermedia ATCC 25611
      were grown anaerobically in suspension cultures, harvested, washed and exposed to
      the benzimidazole lansoprazole at pH values of 4 or 5 before being washed and
      used for standard assays to detect inhibition of catabolic functions, uptake of
      the agent and lethality. RESULTS: Lansoprazole was found to be a bacteriostatic,
      multi-target antimicrobial against F. nucleatum under anaerobic conditions
      inhibitory for amino acid fermentation and also for glycolysis of glucose or
      fructose. ID(50) values for fermentation of amino acids and dipeptides by F.
      nucleatum ranged from 0.05 mM for lysine to 0.25 mM for serine. Fructose
      catabolism was highly sensitive with an ID(50) value of 0.03 mM apparently
      related to high sensitivity of the phosphoenolpyruvate:fructose
      phosphotransferase system, while the ID(50) for glucose catabolism by intact
      cells was some 0.07 mM. Fermentation of aspartate or aspartylaspartate by P.
      intermedia was found to be lansoprazole-sensitive with ID(50) values of about
      0.18 and 0.20 mM, respectively. CONCLUSION: Catabolism of amino acids, dipeptides
      and sugars by oral anaerobes associated with gingivitis are sensitive to the
      inhibitory actions of lansoprazole. Thus, catabolic pathways are potential
      targets for use of benzimidazoles against bacteria involved in gingivitis.

PMID- 16806048
TI  - Plaque biofilms: the effect of chemical environment on natural human plaque
      biofilm architecture.
AB  - The architecture of microbial biofilms especially the outer regions have an
      important influence on the interaction between biofilm and local environment
      particularly on the flux of materials into and out of biofilm compartments and as
      a consequence, biofilm metabolic behaviour. In the case of dental plaque
      biofilms, architecture will determine access of nutrients including acidogenic
      substrates and therapeutic materials to the microbial biomass and to the
      underlying tooth surface. Manipulation of this architecture may offer a means of
      altering mass transfer into the whole biofilm and biomass and raises the
      possibility of improving access of therapeutics. Plaque biofilms formed in vivo
      on human enamel were subjected to a number of different chemical conditions while
      under observation by confocal laser scanning microscopy in reflection mode. In
      this way the outer 50-100 microm or so of the biofilms was examined. Density and
      distribution of biomass were recorded as degree of reflectance. The amount and
      density of biofilm biomass increased from the plaque saliva interface towards the
      interior. Plaque biofilms were robust and little affected by mechanical
      manipulation, high ionic strength or low pH (2.5). Detergent (SLS), however,
      often appeared to either remove biomass and/or dramatically reduce its density.

PMID- 16806049
TI  - Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by
      relative quantification with real-time polymerase chain reaction.
AB  - Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the
      oral and maxillofacial region and has a poor prognosis. Cytokeratin 19 (CK19) is
      a component of cytoskeleton protein. Previous studies have reported abnormal
      expression of CK19 protein in OSCC tissue. This study is to investigate the
      quantitative level of CK19 gene transcript in OSCC tissue as well as its clinical
      significance. Thirty-one OSCC patients (26 males and 5 females) took part in the
      present study, aged 34-78 years (mean 58.2 years). The level of CK19 mRNA was
      detected using fluorescent quantitative real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) in cancerous and paracancerous tissues. The
      relative quantification in cancerous tissue compared with paracancerous tissue
      was calculated using the 2(-DeltaDeltaCt) equation. The level of CK19 mRNA in
      cancerous tissue from OSCC patients was 2.21-fold higher than that in
      paracancerous tissue (P=0.020), and the amplicon was specific without genomic DNA
      contamination. The level of CK19 mRNA correlated significantly with the
      pathological differentiation grade of OSCC tissue (P=0.025), with poorer
      differentiation indicating a higher level of CK19 mRNA. These results suggest
      that fluorescent quantitative real-time RT-PCR is accurate and reliable for the
      detection of CK19 gene transcript levels in OSCC tissue. The level of CK19 mRNA
      was increased in OSCC tissue, and this was significantly correlated with the
      pathological differentiation grade.

PMID- 16806051
TI  - Transport catalysis.
AB  - Carrier linked solute transport through biomembranes is analysed with the
      viewpoint of catalysis. Different from enzymes, in carriers the unchanged
      substrate induces optimum fit in the transition state. The enhanced intrinsic
      binding energy pays for the energy required of the global conformation changes,
      thus decreasing the activation energy barrier. This "induced transition fit"
      (ITF) explains several phenomena of carrier transport, e.g., high or low affinity
      substrate requirements for unidirectional versus exchange, external energy
      requirement for "low affinity" transport, the existence of side specific
      inhibitors to ground states of the carrier, the requirement of external energy in
      active transport to supplement catalytic energy in addition to generate
      electrochemical gradients.

PMID- 16806050
TI  - Modeling human mitochondrial diseases in flies.
AB  - Human mitochondrial diseases are associated with a wide range of clinical
      symptoms, and those that result from mutations in mitochondrial DNA affect at
      least 1 in 8500 individuals. The development of animal models that reproduce the
      variety of symptoms associated with this group of complex human disorders is a
      major focus of current research. Drosophila represents an attractive model, in
      large part because of its short life cycle, the availability of a number of
      powerful techniques to alter gene structure and regulation, and the presence of
      orthologs of many human disease genes. We describe here Drosophila models of
      mitochondrial DNA depletion, deafness, encephalopathy, Freidreich's ataxia, and
      diseases due to mitochondrial DNA mutations. We also describe several genetic
      approaches for gene manipulation in flies, including the recently developed
      method of targeted mutagenesis by recombinational knock-in.

PMID- 16806052
TI  - MMI1 (YKL056c, TMA19), the yeast orthologue of the translationally controlled
      tumor protein (TCTP) has apoptotic functions and interacts with both microtubules
      and mitochondria.
AB  - The yeast orthologue of mammalian TCTP is here proposed to be named Mmi1p
      (microtubule and mitochondria interacting protein). This protein displays about
      50% amino acid sequence identity with its most distantly related orthologs in
      higher organisms and therefore probably belongs to a small class of yeast
      proteins which have housekeeping but so far incompletely known functions needed
      for every eukaryotic cell. Previous investigations of the protein in both higher
      cells and yeast revealed that it is highly expressed during active growth, but
      transcriptionally down-regulated in several kinds of stress situations including
      starvation stress. In human cells, TCTP presumably has anti-apoptotic functions
      as it binds to Bcl-XL in vivo. TCTP of higher cells was also shown to interact
      with the translational machinery. It has acquired an additional function in the
      mammalian immune system, as it is identical with the histamine releasing factor.
      Here, we show that in S. cerevisiae induction of apoptosis by mild oxidative
      stress, replicative ageing or mutation of cdc48 leads to translocation of Mmi1p
      from the cytoplasm to the mitochondria. Mmi1p is stably but reversibly attached
      to the outer surface of the mitochondria and can be removed by digestion with
      proteinase K. Glutathionylation of Mmi1p, which is also induced by oxidants, is
      not a prerequisite or signal for translocation as shown by replacing the only
      cysteine of Mmi1p by serine. Mmi1p probably interacts with yeast microtubules as
      deletion of the gene confers sensitivity to benomyl. Conversely, the deletion
      mutant displays resistance to hydrogen peroxide stress and shows a small but
      significant elongation of the mother cell-specific lifespan. Our results so far
      indicate that Mmi1p is one of the few proteins establishing a functional link
      between microtubules and mitochondria which may be needed for correct
      localization of mitochondria during cell division.

PMID- 16806054
TI  - Bioenergetics of archaea: ancient energy conserving mechanisms developed in the
      early history of life.
AB  - A key component in cellular bioenergetics is the ATP synthase. The enzyme from
      archaea represents a new class of ATPases, the A1AO ATP synthases. They are
      composed of two domains that function as a pair of rotary motors connected by a
      central and peripheral stalk(s). The structure of the chemically-driven motor
      (A1) was solved by small angle X-ray scattering in solution, and the structure of
      the first A1AO ATP synthases (from methanoarchaea) was obtained recently by
      single particle analyses. These studies revealed novel structural features such
      as a second peripheral stalk and a collar-like structure. Interestingly, the
      membrane-embedded electrically-driven motor (AO) is very different in archaea
      with sometimes novel, exceptional subunit composition.

PMID- 16806053
TI  - Uncoupling proteins: a role in protection against reactive oxygen species--or
      not?
AB  - A physiological function of the original uncoupling protein, UCP1, is well
      established: UCP1 is the molecular background for nonshivering thermogenesis. The
      functions of the "novel" UCPs, UCP2 and UCP3, are still not established. Recent
      discussions imply that all UCPs may play a role in protection against reactive
      oxygen species (ROS). Here we examine critically the evidence that UCP1, UCP2 and
      UCP3 are stimulated by ROS (superoxide) or ROS products (4-hydroxy-2-nonenal),
      and that the UCPs actually diminish oxidative damage. We conclude that,
      concerning UCP1, it is unlikely that it has such a role; concerning UCP2/UCP3,
      most evidence for physiologically significant roles in this respect is still
      circumstantial.

PMID- 16806055
TI  - Inhibition of proton pumping by zinc ions during specific reaction steps in
      cytochrome c oxidase.
AB  - Cytochrome c oxidase (CytcO) is a redox-driven proton pump in the respiratory
      chain of mitochondria and many aerobic bacteria. The results from several studies
      have shown that zinc ions interfere with both the uptake and release of protons,
      presumably by binding near the orifice of the proton entrance and exit pathways.
      To elucidate the effect of Zn2+ binding on individual electron and proton
      transfer reactions, in this study, we have investigated the reaction of the fully
      reduced R. sphaeroides CytcO with O2, both with enzyme in detergent solution and
      reconstituted in phospholipid vesicles, and, with and without, Zn2+. The results
      show that addition of Zn2+ at concentrations of < or = 250 microM to the outside
      of the vesicles did not alter the transition rates between intermediates PR (P3)-
      >F3-->O4. However, proton pumping was impaired specifically during the P3-->F3,
      but not during the F3-->O4 transition at Zn2+ concentrations of < or = 25 microM.
      Furthermore, proton pumping during the P3-->F3 transition was typically impaired
      with the "as isolated" CytcO, which was found to contain Zn2+ ions at microM
      concentration. As has already been shown, Zn2+ was also found to obstruct proton
      uptake during the P3-->F3 transition, presumably by binding to a site near the
      orifice of the D-pathway. In this work we found a KI of approximately 1 microM
      for this binding site. In conclusion, the results show that Zn2+ ions bind on
      both sides of CytcO and that binding of Zn2+ at the proton output side
      selectively impairs proton release during the P3-->F3 transition.

PMID- 16806056
TI  - Interaction of the antimicrobial peptide pheromone Plantaricin A with model
      membranes: implications for a novel mechanism of action.
AB  - Plantaricin A (plA) is a 26-residue bacteria-produced peptide pheromone with
      membrane-permeabilizing antimicrobial activity. In this study the interaction of
      plA with membranes is shown to be highly dependent on the membrane lipid
      composition. PlA bound readily to zwitterionic 1-stearoyl-2-oleoyl-sn-glycero-3
      phosphocholine (SOPC) monolayers and liposomes, yet without significantly
      penetrating into these membranes. The presence of cholesterol attenuated the
      intercalation of plA into SOPC monolayers. The association of plA to
      phosphatidylcholine was, however, sufficient to induce membrane permeabilization,
      with nanomolar concentrations of the peptide triggering dye leakage from SOPC
      liposomes. The addition of the negatively charged phospholipid, 1-palmitoyl-2
      oleoyl-sn-glycero-3-phospho-rac-glycerol POPG (SOPC/POPG; molar ratio 8:2)
      enhanced the membrane penetration of the peptide, as revealed by (i) peptide
      induced increment in the surface pressure of lipid monolayers, (ii) increase in
      diphenylhexatriene (DPH) emission anisotropy measured for bilayers, and (iii)
      fluorescence characteristics of the two Trps of plA in the presence of liposomes,
      measured as such as well as in the presence of different quenchers. Despite
      deeper intercalation of plA into the SOPC/POPG lipid bilayer, much less peptide
      induced dye leakage was observed for these liposomes than for the SOPC liposomes.
      Further changes in the mode of interaction of plA with lipids were evident when
      also the zwitterionic phospholipid, 1-palmitoyl-2-oleoyl-sn-glycerol-3
      phosphoethanolaminne (POPE) was present (SOPC/POPG/POPE, molar ratio 3:2:5), thus
      suggesting increase in membrane spontaneous negative curvature to affect the mode
      of association of this peptide with lipid bilayer. PlA induced more efficient
      aggregation of the SOPC/POPG and SOPC/POPG/POPE liposomes than of the SOPC
      liposomes, which could explain the attenuated peptide-induced dye leakage from
      the former liposomes. At micromolar concentrations, plA killed human leukemic T
      cells by both necrosis and apoptosis. Interestingly, plA formed supramolecular
      protein-lipid amyloid-like fibers upon binding to negatively charged phospholipid
      containing membranes, suggesting a possible mechanistic connection between fibril
      formation and the cytotoxicity of plA.

PMID- 16806058
TI  - Abnormal and normal obsessions: a reconsideration.
AB  - Contemporary cognitive approaches to obsession assume that the content of
      clinical obsessions does not differ from non-clinical obsessive intrusions. This
      assumption goes back to a classic study by Rachman and De Silva [(1978). Abnormal
      and normal obsessions. Behaviour Research and Therapy, 16, 233-248]. In the
      present paper, it is argued that Rachman and De Silva did not postulate a
      complete indifference between clinical and non-clinical obsessions. Study 1 is a
      simple statistical analysis of data presented by Rachman and De Silva. This
      analysis suggested that psychologists are able to discriminate clinical and non
      clinical obsessions beyond chance level, merely by looking at the content of
      obsessions. In study 2, a list of 23 clinical and 47 non-clinical obsessions was
      presented to 11 psychotherapists and 90 psychology undergraduates. Both
      therapists and students were able to distinguish clinical and non-clinical
      obsession beyond chance level. It is concluded that some clinical obsessions can
      be identified as being evidently abnormal, and that additional theory and
      research is needed to identify the causes of these recognisable obsessions.

PMID- 16806057
TI  - Molecular determination of liver fibrosis by synchrotron infrared
      microspectroscopy.
AB  - Liver fibrosis is an adaptive response to various injuries and may eventually
      progress to cirrhosis. Although there are several non-invasive methods available
      to monitor the progression of liver fibrogenesis, they cannot reliably detect
      fibrosis in its early stages, when the process can be stopped or reversed by
      removing or eliminating the underlying etiological agent that cause the hepatic
      injury. In this study, early fibrosis alterations were characterized
      biochemically, morphologically, and spectroscopically in a rat bile duct ligation
      (BDL) model. Progressive elevations in serum alanine transaminase (ALT),
      aspartate transaminase (AST), and bilirubin levels in the BDL rats were found
      indicating the dynamic deterioration of hepatocellular function.
      Immunofluorescence microscopy using monoclonal anti-collagen III antibody further
      revealed abnormal intertwined networks of collagen fibres surrounding the portal
      areas and extending into the lobules towards the central veins in all BDL samples
      starting from week one. Synchrotron infrared microspectroscopy of liver sections
      was exploited to generate false color spectral maps based upon a unique and
      strong collagen absorption at 1340 cm(- 1), revealing a collagen distribution
      that correlated very well with corresponding images provided by
      immunofluorescence imaging. We therefore suggest that infrared microspectroscopy
      may provide an additional and sensitive means for the early detection of liver
      fibrosis.

PMID- 16806059
TI  - The contribution of recollection and familiarity to recognition memory
      performance in chronic pain patients.
AB  - This study examines the selective impact of chronic pain on memory functioning in
      a recognition task. Thirty chronic pain patients and 30 healthy control subjects
      performed a yes-no word recognition test. The contribution of recollection and
      familiarity to both groups' performance was compared by means of the
      Remember/Know (R/K) procedure, which distinguishes recognition based on the
      recollection of the encoding episode (R responses) and recognition accompanied by
      a feeling of familiarity (K responses). Chronic pain patients showed a decrease
      in recollection together with an increase in familiarity: indeed, they reported
      less R and more K responses than control subjects. This pattern of performance
      was not related to the overall recognition ability. These findings are consistent
      with the hypothesis of the attentional cost of chronic pain, suggesting a
      selective impact of chronic pain on the most attention-demanding cognitive
      processes, such as recollection. This study emphasises the relevance of specific
      procedures distinguishing the underlying components of memory functioning rather
      than solely global indicators.

PMID- 16806060
TI  - Leber's hereditary optic neuropathy is associated with the mitochondrial ND6
      T14484C mutation in three Chinese families.
AB  - We report here the clinical, genetic, and molecular characterization of three
      Chinese families with maternally transmitted Leber's hereditary optic neuropathy
      (LHON). Clinical and genetic evaluations revealed the variable severity and age
      of-onset in visual impairment in these families. In the affected matrilineal
      relatives, the loss of central vision is bilateral, the fellow eye becoming
      affected either simultaneously (45%) or sequentially (55%). The penetrances of
      vision loss in these pedigrees were 27%, 50%, and 60%, respectively. The age-at
      onset of vision loss in these families was 14, 19, and 24 years, respectively.
      Furthermore, the ratios between affected male and female matrilineal relatives
      were 1:1, 1:1.2, and 1:2, respectively. Mutational analysis of mitochondrial DNA
      revealed the presence of homoplasmic ND6 T14484C mutation, which has been
      associated with LHON. The incomplete penetrance and phenotypic variability
      implicate the involvement of nuclear modifier gene(s), environmental factor(s) or
      mitochondrial haplotype(s) in the phenotypic expression of the LHON-associated
      T14484C mutation in these Chinese pedigrees.

PMID- 16806061
TI  - Imatinib mesylate inhibits platelet derived growth factor stimulated
      proliferation of rheumatoid synovial fibroblasts.
AB  - Synovial fibroblast is the key cell type in the growth of the pathological
      synovial tissue in arthritis. Here, we show that platelet-derived growth factor
      (PDGF) is a potent mitogen for synovial fibroblasts isolated from patients with
      rheumatoid arthritis. Inhibition of PDGF-receptor signalling by imatinib mesylate
      (1muM) completely abrogated the PDGF-stimulated proliferation and inhibited
      approximately 70% of serum-stimulated proliferation of synovial fibroblasts.
      Similar extent of inhibition was observed when PDGF was neutralized with anti
      PDGF antibodies, suggesting that imatinib mesylate does not inhibit pathways
      other than those mediated by PDGF-receptors. No signs of apoptosis were detected
      in synovial fibroblasts cultured in the presence of imatinib. These results
      suggest that imatinib mesylate specifically inhibits PDGF-stimulated
      proliferation of synovial fibroblasts, and that inhibition of PDGF-receptors
      could represent a feasible target for novel antirheumatic therapies.

PMID- 16806062
TI  - Angiopoietin-related growth factor (AGF) supports adhesion, spreading, and
      migration of keratinocytes, fibroblasts, and endothelial cells through
      interaction with RGD-binding integrins.
AB  - Angiopoietin-related growth factor (AGF) is a newly identified member of
      angiopoietin-related proteins (ARPs)/angiopoietin-like proteins (Angptls). AGF
      has been considered as a novel growth factor in accelerating cutaneous wound
      healing, as it is capable of stimulating keratinocytes proliferation as well as
      angiogenesis. But in our paper, we demonstrate that AGF stimulates keratinocytes
      proliferation only at high protein concentration, however, it can potently
      promote adhesion, spreading, and migration of keratinocytes, fibroblasts, and
      endothelial cells. Furthermore, we confirm that the adhesion and migration
      cellular events are mediated by RGD-binding integrins, most possibly the alpha(v)
      containing integrins, by in vitro inhibition assays using synthetic competitive
      peptides. Our results strongly suggest that AGF is an integrin ligand as well as
      a mitogenic growth factor and theoretically participates in cutaneous wound
      healing in a more complex mechanism.

PMID- 16806063
TI  - Design and characterization of a novel cellular prion-derived quenched
      fluorimetric substrate of alpha-secretase.
AB  - Under normal conditions, the cellular prion protein (PrP(c)) undergoes a
      proteolytic attack between amino acids 111 and 112 which gives rise to the N
      terminal secreted N1 fragment and its C-terminal membrane-tethered counterpart
      C1. Importantly, this cleavage precludes the integrity of the neurotoxic 106-126
      sequence. Here, we describe an original and reliable assay based on a quenched
      fluorimetric substrate (JMV2770) encompassing the 111/112 sequence of PrP(c). In
      whole brain homogenate, the JMV2770-hydrolysing activity is optimal at neutral pH
      and sensitive to the metalloprotease inhibitor BB3103 but not to acidic and
      serine protease blockers. JMV2770 is efficiently cleaved by intact HEK293 cells
      and fibroblasts in culture, consistent with an hydrolysis by a typical
      ectoprotease. Overexpressions of alpha-secretases a disintegrin and
      metalloprotease-9 (ADAM9), ADAM10 or TACE (ADAM17) in human cells increase BB3103
      sensitive JMV2770 hydrolysis, while invalidation of ADAM10 and TACE or reduced
      expression of ADAM9 by an antisense approach significantly reduced its cleavage.
      Finally, analysis of JMV2770 hydrolysis following transient transfection of
      ADAM10 or ADAM9 cDNA in ADAM10(-/-) fibroblasts allowed to confirm our previous
      data establishing that ADAM9 does not behave as a genuine alpha-secretase but
      rather acts as an important upstream regulator of ADAM10 activity.

PMID- 16806064
TI  - HB-EGF: increase in the ischemic rat retina and inhibition of osmotic glial cell
      swelling.
AB  - We determined whether the expression of heparin-binding epidermal growth factor
      like growth factor (HB-EGF) in the sensory rat retina alters during ischemia
      reperfusion, and whether HB-EGF affects the osmotic swelling which is a
      characteristic feature of Muller glial cells after ischemia. Transient retinal
      ischemia was induced by elevation of the intraocular pressure for 1 h. Western
      blots revealed an upregulation of HB-EGF in the retina at 1, 3, and 7 days after
      reperfusion. HB-EGF inhibited the swelling of glial cells in retinal slices, via
      stimulation of the synaptic release of glutamate and subsequent activation of
      glial metabotropic glutamate receptors which resulted in an autocrine release of
      purinergic receptor agonists. Finally, activation of A1 receptors resulted in
      opening of glial K(+) and Cl(-) channels. It is suggested that the increased
      expression of HB-EGF and the inhibition of glial cell swelling may be parts of a
      protective role of HB-EGF in the ischemic retina.

PMID- 16806065
TI  - A mammalian promoter model links cis elements to genetic networks.
AB  - An accurate identification of gene promoters remains an important challenge.
      Computational approaches for this problem rely on promoter sequence attributes
      that are believed to be critical for transcription initiation. Here we report a
      probabilistic model that captures two important properties of promoters, not used
      by previous methods, viz., the location preference and co-occurrence of promoter
      elements. Additionally, we found that many of the position-specific DNA elements
      are strongly linked with the function of the gene product. For instance, a highly
      conserved motif CCTTT at -1 position is strongly associated with protein
      synthesis, cellular and tissue development. Our comparative analysis of promoter
      classes reveals that the promoters devoid of CpG islands are more conserved and
      have fewer alternative transcription start sites. The discovered links between
      promoter elements and gene function allows us to infer genetic networks from
      promoter elements. The web server for the PSPA promoter predictor is available at
      /PSPA.

PMID- 16806066
TI  - Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal
      stem cells.
AB  - Estrogen responsiveness of bone formation is mediated by the estrogen receptor
      alpha (ERalpha) in osteoblastic lineage. As osteoblasts arise from the
      multipotent bone marrow stromal (mesenchymal) cells, this study was undertaken to
      observe the ERalpha in primary female adult rat bone marrow mesenchymal stem
      cells (BMSCs). The ERalpha was localized using immunocytochemical analysis in
      identified primary BMSCs. Then, using real-time PCR analysis, we measured the
      expression of ERalpha messenger RNA (mRNA) in BMSCs. ERalpha transcripts showed
      different trends between untreated cultures (control group) and osteogenic
      induced cultures (treated group). In the control group, ERalpha mRNA climbed at
      peak levels at a confluence stage and decreased until day 20, whereas, in the
      treated group, the ERalpha mRNA kept climbing from a low level until day 20.
      Thus, the observed developmental expression of ERalpha mRNA correlates with
      progressive BMSCs growth and osteogenic differentiation and BMSCs may be a
      primary target cell for estrogen in maintaining bone formation.

PMID- 16806067
TI  - Expression and purification of the soluble isoform of human receptor for advanced
      glycation end products (sRAGE) from Pichia pastoris.
AB  - RAGE is a multi-ligand receptor involved in various human diseases including
      diabetes, cancer or Alzheimer's disease. Engagement of RAGE by its ligands
      triggers activation of key cellular signalling pathways such as the MAP kinase
      and NF-kappaB pathways. Whereas the main isoform of RAGE is a transmembrane
      receptor with both extra- and intracellular domains, a secreted soluble isoform
      (sRAGE), corresponding to the extracellular part only, has the ability to block
      RAGE signalling and suppress cellular activation. Administration of sRAGE to
      animal models of cancer or multiple sclerosis blocked successfully tumour growth
      and the course of the autoimmune disease. These findings demonstrate that sRAGE
      may have a potential as therapeutic. We present here a fast and simple
      purification protocol of sRAGE from the yeast Pichia pastoris. The identity of
      the protein was confirmed by mass spectrometry and Western blot. The protein was
      N-glycosylated and 95-98% pure as judged by SDS-PAGE.

PMID- 16806068
TI  - Improved perfusion conditions for patch-clamp recordings on human erythrocytes.
AB  - Various configurations of the patch-clamp method are powerful tools for examining
      the transport of charged solutes across biological membranes. Originally
      developed for the study of relatively large cells which adhere to solid surfaces
      under in vitro culture, these methods have been increasingly applied to small
      cells or organelles in suspension. Under these conditions, a number of
      significant technical problems may arise as a result of the smaller geometry.
      Here, we examined these problems using human erythrocytes infected with the
      malaria parasite, Plasmodium falciparum, a system where experimental differences
      and the technical difficulty of erythrocyte patch-clamp have hindered universal
      agreement on the properties of the induced ion channels. We found that patch
      clamp recordings on infected erythrocytes are especially susceptible to artifacts
      from mechanical perturbations due to solution flow around the cell. To minimize
      these artifacts, we designed a new perfusion chamber whose geometry allows
      controlled solution flow around the fragile erythrocyte. Not only were recordings
      acquired in this chamber significantly less susceptible to perfusion artifacts,
      but the chamber permitted rapid and reversible application of known inhibitors
      with negligible mechanical agitation. Electrophysiological recordings then
      faithfully reproduced several findings made with more traditional methods. The
      new perfusion chamber should also be useful for patch-clamp recordings on blood
      cells, protoplasts, and organelles.

PMID- 16806069
TI  - TSAd interacts with Smad2 and Smad3.
AB  - Smad-dependent signalling initiated by TGFbeta superfamily members can be
      modulated by a variety of interacting proteins. Using yeast two-hybrid, co
      immunoprecipitation, and GST pull-down assays we identified T-cell SH2 adapter
      (TSAd) as a protein that interacts with Smad2 and Smad3. TSAd is an adapter
      protein thought to participate in many different signalling pathways. The
      objective of this study was to elucidate the domains important for interaction
      between TSAd and Smad proteins. Our results suggest a model for TSAd-Smad
      interaction that is facilitated by multiple TSAd domains, but primarily through
      the TSAd type I SH2 domain. Interestingly, we also found that both Smad2 and
      Smad3 interact with the Lck type I SH2 domain, but not the PI3K type III SH2
      domain. This research raises the possibility that interaction between SH2
      containing proteins and Smad proteins may represent another method to modulate
      Smad-dependent signalling.

PMID- 16806070
TI  - Bmcystatin, a cysteine proteinase inhibitor characterized from the tick Boophilus
      microplus.
AB  - The bovine tick Rhipicephalus (Boophilus) microplus is a blood-sucking animal,
      which is responsible for Babesia spp and Anaplasma marginale transmission for
      cattle. From a B. microplus fat body cDNA library, 465 selected clones were
      sequenced randomly and resulted in 60 Contigs. An open reading frame (ORF)
      contains 98 amino acids named Bmcystatin, due to 70% amino acid identity to a
      classical type 1 cystatin from Ixodes scapularis tick (GenBank Accession No. ).
      The Bmcystatin amino acid sequence analysis showed two cysteine residues,
      theoretical pI of 5.92 and M(r) of 11 kDa. Bmcystatin gene was cloned in pET 26b
      vector and the protein expressed using bacteria Escherichia coli BL21 SI.
      Recombinant Bmcystatin (rBmcystatin) purified by affinity chromatography on Ni
      NTA-agarose column and ionic exchange chromatography on HiTrap Q column presented
      molecular mass of 11 kDa, by SDS-PAGE and the N-terminal amino acid sequenced
      revealed unprocessed N-terminal containing part of pelB signal sequence. Purified
      rBmcystatin showed to be a C1 cysteine peptidase inhibitor with K(i) value of 0.1
      and 0.6 nM for human cathepsin L and VTDCE (vitellin degrading cysteine
      endopeptidase), respectively. The rBmcystatin expression analyzed by semi
      quantitative RT-PCR confirmed the amplification of a specific DNA sequence (294
      bp) in the fat body and ovary cDNA preparation. On the other hand, a protein band
      was detected in the fat body, ovary, and the salivary gland extracts using anti
      Bmcystatin antibody by Western blot. The present results suggest a possible role
      of Bmcystatin in the ovary, even though the gene was cloned from the fat body,
      which could be another site of this protein synthesis.

PMID- 16806071
TI  - Calreticulin facilitates the cell surface expression of ABCG5/G8.
AB  - ATP-binding cassette (ABC) G5 (G5) and ABCG8 (G8) heterodimerize and function as
      sterol transporter that promote biliary excretion of neutral sterols. Both G5 and
      G8 interact with a lectin-like chaperone, calnexin (CNX), in the endoplasmic
      reticulum (ER) but the significance of this interaction remains unclear. Here, we
      show that not only CNX, but also its homologue calreticulin (CRT), is involved in
      the biosynthesis of G5/G8 sterol transporter. Both CNX and CRT interacted with
      immature forms of G5 and G8, and stimulated their productive folding by
      inhibiting their degradation. Interestingly, CRT predominantly enhanced the cell
      surface expression of mature G5/G8 whereas CNX did not have a similar effect.
      Inhibitors of N-glycan processing indicated that quality control of G5 and G8
      might be differentially regulated in the ER. These findings clarify the role of
      CNX and CRT in the biosynthesis and quality control of G5/G8 sterol transporter.

PMID- 16806072
TI  - The DNA-binding domain of yeast Hsf1 regulates both DNA-binding and
      transcriptional activities.
AB  - The heat shock transcription factor (HSF) is a key regulator of the heat shock
      response. In Saccharomyces cerevisiae, the transcription activating ability of
      Hsf1 is repressed by its DNA-binding domain, but the detailed mechanism by which
      the inhibitory function is relieved in response to stress remains unknown. In
      this study, we isolated and characterized three hsf1 mutants with temperature
      sensitive mutations in the DNA-binding domain. Two mutations inhibited DNA
      binding activity, leading to decreased expression of target genes. The third
      mutation caused transcriptional defects without affecting DNA binding, and its
      suppressor mutation was located in a region important for sensing heat shock.
      These results indicate that the DNA-binding domain regulates both the DNA-binding
      and transcriptional activities of Hsf1, and suggest that these functions are
      located within discrete regions of the DNA-binding domain.

PMID- 16806073
TI  - Protection of Bcl-2 by salubrinal.
AB  - The drug salubrinal has been identified as an inhibitor of phosphatases that act
      on the eukaryotic translation initiation factor 2 subunit (eIF2alpha). The
      resulting maintenance of protein phosphorylation results in enhanced protection
      from the adverse effects of initiators of the unfolded protein response. We found
      that salubrinal can also interact with the anti-apoptotic protein Bcl-2,
      inhibiting binding of the non-peptidic antagonist HA14-1 and of a porphycene that
      can catalyze Bcl-2 photodamage. As a result, salubrinal offers protection from
      the apoptotic and autophagic effects that can result from loss of Bcl-2 function.

PMID- 16806074
TI  - Novel covalent modifications of alpha-synuclein during the recovery from
      proteasomal dysfunction.
AB  - Proteasomal dysfunction and alpha-synuclein (alpha-syn) have both been implicated
      in the pathogenesis of Parkinson's disease (PD). However, the functional
      relationship between these two remains elusive. Here we show that in human
      neuroblastoma cells, novel variants of alpha-syn with molecular weights of 22-25
      kDa were induced after washout of the reversible proteasome inhibitors. Induction
      of these variants seemed to be a specific response to proteasome dysfunction,
      because the treatment and washout of other protease inhibitor or mitochondrial
      inhibitor did not induce these variants. Importantly, PD-linked alpha-syn
      mutations have effects on the formation of these variants. Recently, O-linked
      glycosylation and monoubiquitylation of alpha-syn have been reported. Despite the
      similarity in molecular weights, biochemical properties of our variants suggest
      that they are unrelated with such modifications. Taken together, these results
      suggest that alpha-syn is regulated by the specific functional state of the
      proteasomes, and PD-linked mutations may affect this regulation.

PMID- 16806075
TI  - Peroxisome proliferator-activated receptor alpha-independent peroxisome
      proliferation.
AB  - Hepatic peroxisome proliferation, increases in the numerical and volume density
      of peroxisomes, is believed to be closely related to peroxisome proliferator
      activated receptor alpha (PPARalpha) activation; however, it remains unknown
      whether peroxisome proliferation depends absolutely on this activation. To verify
      occurrence of PPARalpha-independent peroxisome proliferation, fenofibrate
      treatment was used, which was expected to significantly enhance PPARalpha
      dependence in the assay system. Surprisingly, a novel type of PPARalpha
      independent peroxisome proliferation and enlargement was uncovered in PPARalpha
      null mice. The increased expression of dynamin-like protein 1, but not peroxisome
      biogenesis factor 11alpha, might be associated with the PPARalpha-independent
      peroxisome proliferation at least in part.

PMID- 16806076
TI  - Paraoxonase-1 expression is up-regulated in Down syndrome fetal liver.
AB  - Patients with Down syndrome appear to be protected from the development of
      atherosclerosis. On the contrary, hyperhomocysteinemia is associated with an
      increased risk for atherosclerosis. As hyperhomocysteinemia due to cystathionine
      beta synthase deficiency is associated with a decreased expression of paraoxonase
      1, a major anti-atherosclerotic component secreted by the liver, we aimed to
      analyze the expression of paraoxonase-1 and cystathionine beta synthase in Down
      syndrome fetal liver by quantitative real-time reverse transcriptase-polymerase
      chain reaction. Paraoxonase-1 was up-regulated in Down syndrome fetal liver,
      while cystathionine beta synthase gene expression in Down syndrome fetuses was
      similar to the gene level in control fetuses. Moreover, there was no evidence for
      an association between paraoxonase-1 genotypes influencing paraoxonase-1 gene
      expression and Down syndrome. Since most serum paraoxonase-1 is synthesized in
      the liver, an increase of hepatic paraoxonase-1 expression might be one of the
      factors which could explain the low incidence of atherosclerotic vascular disease
      in Down syndrome.

PMID- 16806077
TI  - Reconstitution of human hypoxia inducible factor HIF-1 in yeast: a simple in vivo
      system to identify and characterize HIF-1alpha effectors.
AB  - Hypoxia inducible factor 1 (HIF-1), the master regulator of hypoxia-activated
      genes, is involved in many diseases and is a valid drug target. In order to
      develop a simple and genetically tractable in vivo system for HIF-1 analysis, we
      tested the inducible expression of both human HIF-1 subunits (HIF-1alpha and
      ARNT) in the yeast Saccharomyces cerevisiae and showed the formation of
      transcriptionally active HIF-1. The use of this system for the identification and
      characterization of HIF-1 effectors was first validated by showing that two
      chemical Hsp90 inhibitors, geldanamycin and radicicol, impaired the activity of
      HIF-1 in yeast. By applying this system in mutant yeast strains, we then
      identified Hsp90 co-chaperones, which were required for HIF-1 activity.
      Furthermore, using yeast strains co-expressing truncated forms of HIF-1alpha with
      ARNT or both HIF-1alpha and ARNT, we characterized fragments of HIF-1alpha that
      acted as dominant negative mutants and suppressed HIF-1 activity.

PMID- 16806078
TI  - The non-steroidal anti-inflammatory drug, diclofenac, inhibits Na(+) current in
      rat myoblasts.
AB  - The inhibitory effect of diclofenac, a non-steroidal anti-inflammatory drug
      (NSAID), on the voltage-gated inward Na+ current (I(Na)) in cultured rat
      myoblasts was investigated using the whole-cell voltage-clamp technique. At
      concentrations of 10 nM-100 microM, diclofenac produced a dose-dependent and
      reversible inhibition of I(Na) with an IC50 of 8.51 microM, without modulating
      the fast activation and inactivation process. The inhibitory effect of diclofenac
      took place at resting channels and increased with more depolarizing holding
      potential. In addition to inhibiting the Na+ current amplitude, diclofenac
      significantly modulated the steady-state inactivation properties of the Na+
      channels, but did not alter the steady-state activation. The steady-state
      inactivation curve was significantly shifted towards the hyperpolarizing
      potential in the presence of diclofenac. Furthermore, diclofenac treatment
      resulted in a fairly slow recovery from inactivation of the Na+ channel. The
      inhibitory effect of diclofenac was enhanced by repetitive pulses and was
      inflected by changing frequency; the blocking effect at higher frequency was
      significantly greater than at lower frequency. Both intracellular and
      extracellular application of diclofenac could inhibit I(Na), indicating that
      diclofenac may exert its channel inhibitory action both inside and outside the
      channel sites. Our data directly demonstrate that diclofenac can inhibit the
      inward Na+ channels in rat myoblasts. Some different inhibitory mechanisms from
      that in neuronal Na+ channels are discussed.

PMID- 16806079
TI  - Phosphorylated extracellular signal-regulated kinase 1/2 is localized to the XY
      body of meiotic prophase spermatocytes.
AB  - We found that phosphorylated extracellular signal-regulated kinase 1/2 (phospho
      ERK1/2) is localized to the XY body of meiotic prophase spermatocytes. A more
      detailed surface spread analysis showed that phospho-ERK1/2 is localized to the
      synaptonemal complex of the XY pair of pachytene spermatocytes or the entire XY
      body of zygotene spermatocytes. In the XY body of meiotic prophase spermatocytes,
      both transcription and homologous recombination are inactivated. These results
      suggest a novel function of ERK1/2 in meiotic sex chromosome inactivation.

PMID- 16806080
TI  - Mechanisms of sterol regulatory element-binding protein-2 (SREBP-2) regulation of
      human prostasin gene expression.
AB  - Prostasin is a glycosylphosphatidylinositol (GPI)-anchored serine protease and a
      suppressor of tumor cell invasion. We recently reported that the human prostasin
      gene is up-regulated by the transcription factor sterol regulatory element
      binding protein-2 (SREBP-2). In the present study, we identified multiple SREBP-2
      binding sites, known as sterol regulatory elements (SREs), located at positions 
      897, -538, +8, +71, and +98 (named SRE-897, SRE-538, SRE+8, SRE+71, and SRE+98)
      in the human prostasin gene promoter. Prostasin promoter-reporter constructs,
      representing serial deletions of the 5'-flanking region of the human prostasin
      gene, were transiently transfected into HEK-293 cells for evaluation of promoter
      activities. The region defined by nucleotides -17 to +232 of the prostasin gene
      promoter was shown to be essential for the basal transcriptional activity of the
      human prostasin gene. Mutagenesis of the five SREs was carried out for evaluation
      of their roles in SREBP-2 up-regulation. SRE+98, a novel functional sterol
      regulatory element, was found to be the major site for the stimulatory response
      of prostasin gene expression to SREBP-2.

PMID- 16806081
TI  - Key adhesin gene in community-acquired methicillin-resistant Staphylococcus
      aureus.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
      possessing the Panton-Valentine leukocidin (PVL) gene (luk(PV)) is associated
      with skin and soft tissue infections, osteomyelitis, and necrotizing pneumonia.
      There are geographically two types of CA-MRSA: one (sequence type ST30) that is
      worldwide (pandemic) and the other (sequence types, e.g., ST1, ST8 or ST80) that
      is continent-specific. The pandemic type, but not continent-specific type,
      possessed the bone sialoprotein-adhesin gene (bbp), which was associated with
      osteomyelitis. No recent hospital-acquired MRSA had the bbp gene, while past PVL
      positive nosocomial outbreak-derived strains did possess it. The collagen-adhesin
      gene (cna) was associated with pandemic CA-MRSA, though with positive cases even
      in continent-specific CA-MRSA and PVL-negative Japanese region-specific CA-MRSA.
      Thus, the pandemic type is characterized by the combination of luk(PV) and bbp
      (and cna) genes. A specific real-time PCR assay for the bbp gene was developed,
      and dual assay for bbp and luk(PV) in one test tube became possible.

PMID- 16806082
TI  - Double minute chromosomes in mouse methotrexate-resistant cells studied by atomic
      force microscopy.
AB  - Double minute chromosomes (DMs) are acentric, autonomously replicating extra
      chromosomes and frequently mediate gene amplification in tumor and drug resistant
      cells. Atomic force microscopy (AFM) is a powerful tool in microbiology. We used
      AFM to explore the ultrastructure of DMs in mouse fibroblasts 3T3R500. DMs in
      various phases of cell cycle were also studied in order to elucidate the
      mechanisms of their duplication and separation. Metaphase spread and induced
      premature condensed chromosomes (PCCs) were observed under the AFM. DMs were
      detected to be composed of two compact spheres linked by fibers. The fibers of
      DMs directly connected with metaphase chromosomes were observed. Many single
      minutes and few DMs were detected in G1 PCCs, while more DMs were detected in S
      PCCs than in G1 PCCs. Besides, all of the DMs in G2 PCCs were coupled. Our
      present results suggested that DMs might divide into single-minutes during or
      before G1-phase, followed by duplication of the single-minutes in S-phase.
      Moreover, we introduced a new powerful tool to study DMs and got some ideal
      results.

PMID- 16806083
TI  - ZNF325, a novel human zinc finger protein with a RBaK-like RB-binding domain,
      inhibits AP-1- and SRE-mediated transcriptional activity.
AB  - Mitogen-activated protein kinase (MAPK) signal transduction pathways are among
      the most widespread mechanisms of eukaryotic cell regulation. The zinc-finger
      containing transcription factors have been previously revealed to be involved in
      the regulation of the MAPK signaling pathways. Here, we have identified a novel
      human zinc-finger transcriptional repressor, ZNF325, that contains a RBaK-like RB
      binding domain and 15 tandem repeated C2H2 type zinc fingers. Northern blot
      analysis indicates that a 2.7 kb transcript specific for ZNF325 is widely
      expressed in all tissues examined at adult stage and in most of the embryonic
      tissues. Overexpression of ZNF325 in COS-7 cells inhibits the transcriptional
      activities of AP-1 and SRE. The deletion and RNAi analysis indicate that the C2H2
      zinc finger motifs represent the basal transcriptional repressive activity. These
      results indicate that the ZNF325 protein may act as a novel transcription
      repressor in MAPK signaling pathway to mediate cellular functions.

PMID- 16806084
TI  - Suppressive effect on hepatocyte differentiation of hepatitis C virus core
      protein.
AB  - The influence of hepatitis C virus (HCV) protein(s) on cellular differentiation
      remains to be clarified. Using murine normal liver epithelial cells, we
      investigated whether HCV core protein affects differentiation into hepatocytes.
      Mock and HCV core-expressing cells were stimulated with oncostatin M (OSM) and
      dexamethasone, and the degree of differentiation was evaluated by measuring the
      expression of albumin and tyrosine aminotransferase (TAT). Lower amounts after
      stimulation were found in HCV core-expressing cells than in mock cells.
      Phosphorylation of the signal transducer and activator transcription factor 3
      (STAT3) was prevented by the HCV core under OSM stimulation. Reporter gene assay
      revealed that the HCV core/Janus kinase (JAK) interaction directly suppressed the
      OSM-dependent JAK-STAT signal transduction. Furthermore, expression of OSM
      receptor beta (OSMRbeta) after stimulation was prevented by the HCV core. In
      conclusion, the HCV core may suppress differentiation into hepatocytes via
      inhibition of the JAK-STAT pathway and OSMRbeta expression.

PMID- 16806085
TI  - Alterations in transporter expression in liver, kidney, and duodenum after
      targeted disruption of the transcription factor HNF1alpha.
AB  - The transcription factor hepatocyte nuclear factor 1alpha (HNF1alpha) is involved
      in regulation of glucose metabolism and transport, and in the expression of
      several drug and bile acid metabolizing enzymes. Targeted disruption of the
      HNF1alpha gene results in decreased Cyp1a2, and Cyp2e1 expression, and increased
      Cyp4a1 and Cyp7a1 expression, suggesting these enzymes are HNF1alpha target
      genes. Since hepatic metabolism can be coordinately linked with drug and
      metabolite transport, this study aims to demonstrate whether HNF1alpha regulates
      expression of a variety of organic anion and cation transporters through
      utilization of an HNF1alpha-null mouse model. Expression of 32 transporters,
      including members of the Oat, Oatp, Oct, Mrp, Mdr, bile acid and sterolin
      families, was quantified in three different tissues: liver, kidney, and duodenum.
      The expression of 17 of 32 transporters was altered in liver, 21 of 32 in kidney,
      and 6 of 32 in duodenum of HNF1alpha-null mice. This includes many novel
      observations, including marked downregulation of Oats in kidney, as well as
      upregulation of many Mrp and Mdr family members in all three tissues. These data
      indicate that disruption of HNF1alpha causes a marked attenuation of several Oat
      and Oatp uptake transporters in liver and kidney, and increased expression of
      efflux transporters such as Mdrs and Mrps, thus suggesting that HNF1alpha is a
      central mediator in regulating hepatic, renal, and intestinal transporters.

PMID- 16806086
TI  - Bucillamine induces glutathione biosynthesis via activation of the transcription
      factor Nrf2.
AB  - The properties of bucillamine, a synthetic antioxidant, have been attributed
      mainly to the donation of thiol groups to glutathione (GSH). We recently
      demonstrated that glutamate-cysteine ligase catalytic subunit (GCLC), the rate
      limiting enzyme of GSH biosynthesis, and the multidrug-resistance-associated
      protein 2 (Mrp2/MRP2) are coordinately induced in response to xenobiotic through
      the activation of the antioxidant-response element (ARE) by nuclear factor
      erythroid 2 p45-related factor (Nrf2). We tested the hypothesis that bucillamine
      and its oxidized metabolite SA 981 also activate the Nrf2 pathway, thereby
      increasing glutathione biosynthesis in human HepG2 and murine Hepa 1-6 hepatoma
      cell lines, through the induction of the GCLC enzyme as well as the Mrp2/MRP2
      transporter, which mediates the excretion of glutathione and its conjugates from
      hepatocytes. Both bucillamine and SA 981 produced a significant dose-dependent
      increase in the mRNA levels of Mrp2/MRP2 and GCLC after 24 h. The levels of the
      transcription factor Nrf2 in the nuclei were maximal at 3 h, remained elevated at
      6 h, and decreased to control values at 24 h in both cell lines. Moreover, both
      bucillamine and SA 981 significantly increased the expressions of Mrp2/MRP2 and
      GCLC proteins in both cell lines. Finally, in both cell lines, bucillamine and SA
      981 increased the GSH content two- to three-fold. These results demonstrate that
      bucillamine and SA 981 activate the ARE-ARE pathway increasing the expression of
      ARE-driven genes such as those of GCLC and Mrp2/MRP2. The role of bucillamine as
      a chemopreventive agent against cancer remains to be elucidated.

PMID- 16806087
TI  - Differential anti-proliferative actions of peroxisome proliferator-activated
      receptor-gamma agonists in MCF-7 breast cancer cells.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation has been
      a new approach to cancer therapy. In the present study, we investigated the
      effects of two structurally different PPARgamma agonists, rosiglitazone and KR
      62980 on MCF-7 breast cancer cells. Both agonists inhibited the cell
      proliferation and colony formation via apoptosis. PTEN expression was increased
      with decreased Akt phosphorylation by the agonists, whereas agonists actions were
      abolished in PTEN knockdown cells, indicating the critical role of PTEN in the
      anti-proliferative effects of PPARgamma activation. Rosiglitazone induced the MCF
      7 cell differentiation but KR-62980 did not alter the differentiation pattern
      with little effects on the lipid accumulation and the expression of lipogenesis
      markers. These results suggest that PPARgamma activation may result in the
      inhibition of cell proliferation and/or induction of cell differentiation
      depending on the type of PPARgamma agonists, and that KR-62980 may be useful in
      breast cancer therapy by inducing apoptosis.

PMID- 16806088
TI  - Down-regulation of estrogen receptor-alpha in MCF-7 human breast cancer cells
      after proteasome inhibition.
AB  - The eukaryotic proteasome is a 26S ATP-dependent proteolytic complex, which
      possesses chymotrypsin-like, trypsin-like and peptidyl glutamyl peptide hydrolase
      (PGPH) activities, which enable the proteasome to degrade all short-lived and
      many long-lived proteins, and consequently regulate a myriad of activities in
      cells. In this study, we observed that inhibition of the proteasome, and more
      specifically, inhibition of the chymotrypsin-like activity of the proteasome, in
      MCF-7 human breast cancer cells resulted in selective down-regulation of the
      nuclear estrogen receptor-alpha (ERalpha). Our data indicated that estrogen had
      no effect, whereas the ERalpha antagonist, tamoxifen, reduced the amount of
      ERalpha that could be subjected to down-regulation after proteasome inhibition.
      Furthermore, our data demonstrated that protein synthesis was required for the
      down-regulation of ERalpha to occur. Collectively, these data indicate the
      existence of a proteasome-dependent mechanism that is utilized by MCF-7 cells to
      maintain a steady-state level of ERalpha.

PMID- 16806089
TI  - Green tea flavonols inhibit glucosidase II.
AB  - Green tea is getting into the focus of scientific interest due to its beneficial
      health effects, most of which are attributed to its catechin content.
      Polyphenolic tea catechins have antioxidant, antiproliferative, antiangiogenic
      and proapoptotic effects, which makes them promising anticancer compounds. Other
      poly-hydroxy molecules have similar antitumor potentials through the inhibition
      of glucosidase II, which affects the glycoprotein maturation and quality control
      in the endoplasmic reticulum. We investigated the effect of tea catechins on
      glucosidase II activity in rat liver microsomes using 4-methylumbelliferyl
      glucoside and 4-nitrophenyl glucoside as substrates. A concentration-dependent
      inhibition with non-competitive kinetics was found. The IC50 and Ki values for
      certain tea catechins were comparable with those of N-butyldeoxynojirimycin, the
      widely used glucosidase inhibitor. The possible interference of tea catechins
      with the glycoprotein processing in the endoplasmic reticulum should be
      considered as a potential mechanism of their dietary or pharmacological effects.

PMID- 16806090
TI  - Brief sleep after learning keeps emotional memories alive for years.
AB  - BACKGROUND: Sleep after learning supports memory consolidation. However, long
      lasting memory effects of sleep have not yet been investigated. Postlearning
      sleep may be particularly involved in the long-term retention of emotional
      memories and could thereby contribute to the development of posttraumatic stress
      disorder (PTSD), a disease thought to result from overconsolidation of traumatic
      memories. METHODS: Subjects (healthy men) who had learned neutral and emotional
      texts immediately before sleeping or remaining awake for the subsequent 3 hours
      were recontacted after 4 years for long-term memory assessment (forced-choice
      recognition test). RESULTS: Sleep following learning compared with wakefulness
      enhanced memory for emotional texts after 4 years (p = .001). No such enhancement
      was observed for neutral texts (p = .571). CONCLUSIONS: Brief periods of sleep
      immediately following learning cause preservation of emotional memories over
      several years. Sleep deprivation in the immediate aftermath of traumatic events
      could be a promising therapeutic measure to prevent PTSD.

PMID- 16806091
TI  - Microtubule stabilizer ameliorates synaptic function and behavior in a mouse
      model for schizophrenia.
AB  - BACKGROUND: Recent data suggest that cytoskeletal defects may play a role in
      schizophrenia. We previously imitated features of schizophrenia in an animal
      model by disrupting gene coding for a microtubule-associated protein called STOP.
      STOP-null mice display synaptic defects in glutamatergic neurons, hyper
      dopaminergy, and severe behavioral disorders. Synaptic and behavioral deficits
      are amended by neuroleptic treatment in STOP-null mice, providing an attractive
      model to test new antipsychotic agents. We examined the effects of a taxol
      related microtubule stabilizer, epothilone D. METHODS: Mice were treated either
      with vehicle alone or with epothilone D. Treatment effects on synaptic function
      were assessed using electron-microscopy quantification of synaptic vesicle pools
      and electrophysiology in the CA1 region of the hippocampus. Dopamine transmission
      was investigated using electrochemical assays. Behavior was principally assessed
      using tests of maternal skills. RESULTS: In STOP-null mice, treatment with
      epothilone D increased synaptic vesicle pools, ameliorated both short- and long
      term forms of synaptic plasticity in glutamatergic neurons, and had a dramatic
      beneficial effect on mouse behavior. CONCLUSIONS: A microtubule stabilizer can
      have a beneficial effect on synaptic function and behavior, suggesting new
      possibilities for treatment of schizophrenia.

PMID- 16806092
TI  - Aripiprazole blocks reinstatement of cocaine seeking in an animal model of
      relapse.
AB  - BACKGROUND: Aripiprazole (Abilify) is an atypical antipsychotic drug primarily
      characterized by partial agonist activity at dopamine (DA) D2 receptors and low
      side effects. Based on pharmacologic properties that include a stabilization of
      mesocorticolimbic DA activity, a pathway implicated in addiction, aripiprazole
      was tested for its ability to prevent relapse to cocaine seeking in rats.
      METHODS: We assessed the dose-dependent effects of aripiprazole on conditioned
      cue-induced and cocaine-primed reinstatement of drug-seeking behavior following
      chronic intravenous cocaine self-administration in an animal model of relapse.
      RESULTS: Aripiprazole potently and dose-dependently attenuated responding on the
      previously cocaine-paired lever during both reinstatement conditions, with
      slightly greater efficacy at reducing conditioned-cued reinstatement.
      Aripiprazole was effective at doses that failed to alter cocaine self
      administration, food self-administration, reinstatement of food-seeking behavior,
      or basal locomotor activity, suggesting selective effects of aripiprazole on
      motivated drug-seeking behavior. CONCLUSIONS: These results in a relapse model
      show that aripiprazole can block cocaine seeking without affecting other
      behaviors. The D2 partial agonist properties of aripiprazole likely account for
      the blockade of reinstatement of cocaine-seeking behavior. Given its established
      efficacy and tolerability as a treatment for psychosis, aripiprazole may be an
      excellent therapeutic choice for reducing craving and preventing relapse in
      people with cocaine dependency.

PMID- 16806093
TI  - Region specific regulation of NR1 in rhesus monkeys following chronic
      antipsychotic drug administration.
AB  - BACKGROUND: Altered NMDA receptor subunit protein levels have been reported in
      various regions of the schizophrenic brain; however, chronic antipsychotic
      administration in schizophrenic subjects may confound interpretation. METHODS:
      The effects of chronic antipsychotic drug administration (haloperidol and
      clozapine) on protein levels of NR1, NR2A and NR2B proteins were evaluated in the
      nucleus accumbens (NAc), putamen (PUT), dorsolateral prefrontal cortex (DLPFC),
      superior temporal gyrus (STG), and entorhinal cortex (EC) of rhesus monkeys using
      Western blot analysis. RESULTS: Haloperidol administration significantly
      decreased NR1 expression in the DLPFC. In contrast, NR2B expression was not
      affected by antipsychotic administration in any brain region examined. NR2A was
      not reliably detected in any of the brain regions. CONCLUSIONS: Results indicate
      that the NR1 subunit in the DLPFC may be a substrate for antipsychotic action and
      that glutamatergic hypofunction in the DLPFC commonly associated with cognitive
      dysfunction in schizophrenia may be associated with haloperidol administration.

PMID- 16806094
TI  - Cognitive and physical activity differently modulate disease progression in the
      amyloid precursor protein (APP)-23 model of Alzheimer's disease.
AB  - BACKGROUND: In aging mice, activity maintains hippocampal plasticity and adult
      hippocampal neurogenesis at a level corresponding to a younger age. Here we
      studied whether physical exercise and environmental enrichment would also affect
      brain plasticity in a mouse model of Alzheimer's disease (AD). METHODS: Amyloid
      precursor protein (APP)-23 mice were housed under standard or enriched conditions
      or in cages equipped with a running wheel. We assessed beta-amyloid plaque load,
      adult hippocampal neurogenesis, spatial learning, and mRNA levels of trophic
      factors in the brain. RESULTS: Despite stable beta-amyloid plaque load, enriched
      living mice showed improved water maze performance, an up-regulation of
      hippocampal neurotrophin (NT-3) and brain-derived neurotrophic factor (BDNF) and
      increased hippocampal neurogenesis. In contrast, despite increased bodily
      fitness, wheel-running APP23 mice showed no change in spatial learning and no
      change in adult hippocampal neurogenesis but a down-regulation of hippocampal and
      cortical growth factors. CONCLUSIONS: We conclude that structural and molecular
      prerequisites for activity-dependent plasticity are preserved in mutant mice with
      an AD-like pathology. Our study might help explain benefits of activity for the
      aging brain but also demonstrates differences between physical and more cognitive
      activity. It also suggests a possible cellular correlate for the dissociation
      between structural and functional pathology often found in AD.

PMID- 16806095
TI  - Galantamine improves cognition in schizophrenic patients stabilized on
      risperidone.
AB  - BACKGROUND: Cognition in schizophrenia is impaired in a variety of cognitive
      domains. Galantamine, a cholinesterase inhibitor with putative nicotinic agonist
      like effects, improves cognition in Alzheimer's patients. METHODS: Sixteen
      schizophrenic or schizoaffective patients stabilized on risperidone were
      administered galantamine (n=8) or placebo (n=8) in a randomized, double-blind
      trial. The Repeatable Battery for Assessment of Neuropsychological Status (RBANS)
      assessed changes in cognitive performance over an eight-week treatment interval.
      RESULTS: Clinical symptoms improved in both groups during the trial with no
      evidence that galantamine exacerbated extrapyramidal symptoms. Patients treated
      with galantamine experienced an overall improvement in cognitive performance
      (RBANS Total scale score; galantamine = 12.1 +/- 12.8 SD, placebo = .5 +/- 13.5,
      t = 2.32, p < .04). Confidence intervals suggest that RBANS Attention and Delayed
      Memory subscale performance was robustly improved in galantamine patients by
      approximately one standard deviation, effectively normalizing cognitive
      performance in these domains. CONCLUSIONS: Adjunctive treatment with galantamine
      improves memory and attention in patients with schizophrenia who are stabilized
      on risperidone, providing the opportunity to improve functional outcome in these
      patients.

PMID- 16806096
TI  - Comparison of parent and teacher reports of attention-deficit/hyperactivity
      disorder symptoms from two placebo-controlled studies of atomoxetine in children.
AB  - BACKGROUND: The validity of parent reports regarding children's attention
      deficit/hyperactivity disorder (ADHD) symptoms has been questioned. This study
      assessed whether parent reports were as sensitive as teacher reports to document
      change in ADHD symptoms during clinical trials with atomoxetine. METHODS: Data
      were compared from two randomized, double-blind, placebo-controlled clinical
      trials of atomoxetine using different versions (parent or teacher) of the same
      rating scale (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV [parent or
      teacher] Version: Investigator Administered and Scored - ADHD RS). Exclusion
      criteria included history of bipolar disorder, psychosis, seizures, alcohol
      abuse, or positive drug screen. Patients (6-16 years old) were treated with
      atomoxetine (titrated to a maximum dose of 1.8 mg/kg/day) administered once daily
      for up to 7 weeks. Parent and teacher ratings were compared using an analysis of
      covariance (ANCOVA) model. RESULTS: The analysis (n = 318) showed that treatment
      effects (mean change, baseline to endpoint) were similar between parent and
      teacher ratings (total, p = .762; inattention, p = .519; hyperactive/impulsive, p
      = .955). Effect sizes also were similar based on total scores (parent ratings =
      .69; teacher ratings = .63). CONCLUSIONS: Parent reports are as sensitive as
      teacher reports in assessing the efficacy of long-acting pharmacologic treatment
      for ADHD in children during clinical trials using the nonstimulant atomoxetine.

PMID- 16806097
TI  - Intra-subject variability in attention-deficit hyperactivity disorder.
AB  - BACKGROUND: This study is based on a comprehensive survey of the
      neuropsychological attention-deficit hyperactivity disorder (ADHD) literature and
      presents the first psychometric analyses of different parameters of intra-subject
      variability (ISV) in patients with ADHD compared to healthy controls, using the
      Continuous Performance Test, a Go-NoGo task, a Stop Signal Task, as well as N
      back tasks. METHODS: Data of 57 patients with ADHD and 53 age- and gender-matched
      controls were available for statistical analysis. Different parameters were used
      to describe central tendency (arithmetic mean, median), dispersion (standard
      deviation, coefficient of variation, consecutive variance), and shape (skewness,
      excess) of reaction time distributions, as well as errors (commissions and
      omissions). RESULTS: Group comparisons revealed by far the strongest effect sizes
      for measures of dispersion, followed by measures of central tendency, and by
      commission errors. Statistical control of ISV reduced group differences in the
      other measures substantially. One (patients) or two (controls) principal
      components explained up to 67% of the inter-individual differences in intra
      individual variability. CONCLUSIONS: Results suggest that, across a variety of
      neuropsychological tests, measures of ISV contribute best to group
      discrimination, with limited incremental validity of measures of central tendency
      and errors. Furthermore, increased ISV might be a unitary construct in ADHD.

PMID- 16806098
TI  - Tryptophan hydroxylase-1 gene variants associated with schizophrenia.
AB  - BACKGROUND: Serotonin (5-HT) has been implicated in the pathophysiology of
      schizophrenia. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the
      biosynthesis of serotonin (5-HT), and as such it might be related to the
      pathogenesis of schizophrenia. Two isoforms are known, TPH-1 and TPH-2. TPH-1
      association with schizophrenia is debated. METHODS: A case-control design was
      employed for gene-disease association in 155 schizophrenic psychosis patients and
      253 healthy controls, all North European Caucasians. Six single nucleotide
      polymorphisms (SNPs) with a haplotype block structure spanning over 23 kb of the
      total TPH-1 29 kb were analyzed. Linkage disequilibrium and haplotype analyses
      were performed. Bonferroni correction was used for multiple testing. RESULTS:
      Single marker association analyses showed two SNPs significantly associated with
      schizophrenia. Several haplotypes were associated with the disease. A "sliding
      window" analysis attributed the strongest disease association to a haplotype
      configuration localized between the promoter region and intron 3. CONCLUSIONS:
      Our data indicate that TPH-1 associates with schizophrenia. It appears that
      specific combinations of promoter variants vis-a-vis gene transcript variants
      contribute to genetic predisposition to the disease.

PMID- 16806099
TI  - Candidate gene polymorphisms in the serotonergic pathway: influence on depression
      symptomatology in an elderly population.
AB  - BACKGROUND: Depressed mood is a major concern in the elderly, with consequences
      for morbidity and mortality. Previous studies have demonstrated that genetic
      factors in depression and subsyndromal depressive symptoms are no less important
      in the elderly than during other life stages. Variations in genes included in the
      serotonin system have been suggested as risk factors for various psychiatric
      disorders but may also serve as candidates for normal variations in mood.
      METHODS: This study included 684 elderly Danish twins to investigate the
      influence of 11 polymorphisms in 7 serotonin system genes on the mean level of
      depression symptomatology assessed over several years, reflecting individuals'
      underlying mood level. RESULTS: A suggestive association of sequence variations
      in genes responsible for the synthesis (TPH), recognition (5-HTR2A), and
      degradation (MAOA) of serotonin with depression symptomatology was found,
      although the effect was generally restricted to men. We also found that a
      specific haplotype in VMAT2, the gene encoding the vesicular monoamine
      transporter, was significantly associated with depression symptoms in men (p=
      .007). CONCLUSIONS: These results suggest that variations in genes encoding the
      components of serotonin metabolism may influence the basic mood level and that
      different genetic factors may apply in men and women.

PMID- 16806100
TI  - Methylphenidate preferentially increases catecholamine neurotransmission within
      the prefrontal cortex at low doses that enhance cognitive function.
AB  - BACKGROUND: Low doses of psychostimulants, such as methylphenidate (MPH), are
      widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD).
      Surprisingly little is known about the neural mechanisms that underlie the
      behavioral/cognitive actions of these drugs. The prefrontal cortex (PFC) is
      implicated in ADHD. Moreover, dopamine (DA) and norepinephrine (NE) are important
      modulators of PFC-dependent cognition. To date, the actions of low-dose
      psychostimulants on PFC DA and NE neurotransmission are unknown. METHODS: In vivo
      microdialysis was used to compare the effects of low-dose MPH on NE and DA efflux
      within the PFC and select subcortical fields in male rats. Doses used (oral, 2.0
      mg/kg; intraperitoneal, .25-1.0 mg/kg) were first determined to produce
      clinically relevant plasma concentrations and to facilitate both PFC-dependent
      attention and working memory. RESULTS: At low doses that improve PFC-dependent
      cognitive function and that are devoid of locomotor-activating effects, MPH
      substantially increases NE and DA efflux within the PFC. In contrast, outside the
      PFC these doses of MPH have minimal impact on NE and DA efflux. CONCLUSIONS: The
      current observations suggest that the therapeutic actions of low-dose
      psychostimulants involve the preferential activation of catecholamine
      neurotransmission within the PFC.

PMID- 16806101
TI  - RETRACTED: Chronic administration of carbamazepine down-regulates AP-2 DNA
      binding activity and AP-2alpha protein expression in rat frontal cortex.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted
      at the request of author Stanley Rapoport, with approval from Biological
      Psychiatry Editor, John H. Krystal, MD.The National Institutes of Health has
      found that Dr. Jagadeesh S. Rao engaged in research misconduct by falsifying data
      in Figures 1, 3, and 5 of the aforementioned manuscript. No other authors were
      implicated in the data falsification

PMID- 16806102
TI  - Biological risk factors in pediatric bipolar disorder.
AB  - BACKGROUND: The current study attempted to determine whether neurodevelopmental
      and acquired brain abnormalities are more common in pediatric bipolar disorder
      (PBD). METHODS: The study sample consisted of 98 subjects with a mean age of 11.5
      +/- 3.3 years comprising three demographically matched groups: healthy controls
      (HC, n = 28), subjects with bipolar disorder - Type I (PBD, n = 37), and bipolar
      disorder - Type I combined with attention deficit hyperactivity disorder
      (PBD+ADHD, n = 33). Family history of PBD was determined using the Family History
      Screen. Additional measures were administered to assess the history on perinatal
      risk, development milestones, serious physical illnesses, and head injury.
      RESULTS: Logistic regression showed that that family history and perinatal risk
      factors predicted the diagnosis of PBD. PBD diagnosis was 15 times higher among
      those with a family history of BD. Second, for every additional perinatal risk
      factor such as prenatal exposure to drugs or birth complications, the risk of
      having a PBD diagnosis increased more than six-fold. CONCLUSIONS: Having a
      positive familial history of BD in a first degree relative and perinatal insults
      may elevate the risk for developing PBD. Presence of these risk factors,
      especially in the context of clinical signs of affect dysregulation, should alert
      clinicians to screen for PBD.

PMID- 16806103
TI  - Association between alpha-2a-adrenergic receptor gene and ADHD inattentive type.
AB  - BACKGROUND: Previous investigations have demonstrated that an MspI polymorphism
      at the adrenergic alpha2A receptor gene (ADRA2A) is associated with severity of
      attention-deficit/hyperactivity disorder (ADHD) inattentive symptoms in clinical
      samples composed mainly of subjects with ADHD, combined type. This study aimed to
      investigate the association between this ADRA2A polymorphism and attention
      deficit/hyperactivity disorder-inattentive type (ADHD-I) in a nonreferred sample.
      METHODS: In a case-control study, we assessed a sample of 100 children and
      adolescents with ADHD-I and 100 non-ADHD controls. Cases and controls were
      matched by gender and age and were screened by using teacher reports in a revised
      version of the Swanson, Nolan, and Pelham rating scale at 12 schools. Psychiatric
      diagnoses were derived through structured diagnostic interviews. RESULTS:
      Homozygous subjects for the G allele at the ADRA2A had significantly higher odds
      ratio (OR) for ADHD-I than did those with other genotypes (CC + CG genotypes),
      even after adjusting for potential confounders (p = .02; OR = 3.78; 95%
      confidence interval = 1.23-11.62). In family-based analyses, no significant
      associations were detected. CONCLUSIONS: Our results suggest that the ADRA2A may
      be associated with ADHD-I, replicating previous findings from clinical samples
      that have suggested the importance of this gene for the dimension of inattention.
      In addition, these results support the role of the noradrenergic system in ADHD.

PMID- 16806104
TI  - Lithium regulates glycogen synthase kinase-3beta in human peripheral blood
      mononuclear cells: implication in the treatment of bipolar disorder.
AB  - BACKGROUND: Bipolar disorder has been linked to alterations in the
      multifunctional enzyme glycogen synthase kinase-3beta (GSK3beta). The mood
      stabilizer lithium inhibits GSK3beta in vitro and in mouse brain, and this is
      currently the strongest known potential therapeutic target of lithium. We tested
      whether lithium modified GSK3beta in vivo or in vitro in peripheral blood
      mononuclear cells (PBMCs) from healthy control and bipolar disorder subjects.
      METHODS: The PBMCs were obtained from 23 healthy control subjects, 9 bipolar
      subjects currently treated with lithium, and 13 lithium-free bipolar subjects.
      Immunoblot analyses were used to measure the inhibited, serine9-phosphorylated
      GSK3beta. RESULTS: The level of phospho-Ser9-GSK3beta in PBMCs was regulated by
      agents that modified kinases and phosphatases acting on GSK3beta and was
      increased by in vitro lithium treatment. More important, phospho-Ser9-GSK3beta
      levels were eightfold higher in PBMCs from lithium-treated bipolar than healthy
      control subjects. CONCLUSIONS: Signaling pathways regulating serine9
      phosphorylation of GSK3beta can be studied in human PBMCs. Both in vitro and in
      vivo therapeutic lithium treatment is associated with a large increase in phospho
      Ser9-GSK3beta in PBMCs. Therefore, the inhibitory serine9-phosphorylation of
      GSK3beta in human PBMCs may provide a biochemical marker to evaluate the
      association between GSK3beta inhibition and therapeutic responses to lithium
      treatment.

PMID- 16806105
TI  - Nested association between genetic variation in tryptophan hydroxylase II,
      bipolar affective disorder, and suicide attempts.
AB  - BACKGROUND: Bipolar affective disorder (BPAD) is a common mental illness that is
      strongly associated with suicide. Suicidal behavior is thought to result from an
      interaction of genetic, neurobiological, and psychosocial factors and tends to
      cluster in families, suggesting specific familial factors distinct from those
      that underlie BPAD itself. Serotonin signaling has long been implicated in both
      BPAD and suicide, and the gene encoding the brain-expressed isoform of tryptophan
      hydroxlyase (TPH2) has been described. Markers in TPH2 have been implicated in
      suicide and major depressive disorder, but the results across studies are
      inconsistent. No studies have examined TPH2 in large samples of subjects with
      BPAD and suicide attempts (SA). We tested for a relationship between genetic
      variation in TPH2 and risk for BPAD and SA in a large family sample. METHODS: The
      sample consisted of 2018 members of 670 families, ascertained through a sibling
      pair affected with bipolar I, bipolar II, or schizoaffective-bipolar disorder and
      diagnosed under DSM-III/IV criteria. Three single nucleotide polymorphisms
      representing the common haplotypes spanning TPH2 were analyzed. RESULTS: Single
      marker analysis failed to detect significant genetic association with BPAD or SA,
      but the number of informative families was small. Haplotype analysis showed
      significant association with both BPAD and SA, and the same haplotype was
      significantly associated with both BPAD and SA in a replication sample. Case-only
      analysis, stratified by SA, suggested that TPH2 was not an independent genetic
      risk factor for SA in this sample. CONCLUSIONS: The TPH2 might contribute to the
      risk of both BPAD and SA in families with BPAD. Further studies are needed to
      uncover the functional genetic variation that accounts for the observed
      associations.

PMID- 16806106
TI  - Placental trophoblast inclusions in autism spectrum disorder.
AB  - BACKGROUND: Microscopic examination of placental tissue may provide a route to
      assessing risk and understanding underlying biology of autism. METHODS:
      Occurrence of a distinctive microscopic placental morphological abnormality, the
      trophoblast inclusion, was assessed using archived placental tissue. The rate of
      occurrence of trophoblast inclusion-positive slides observed for 13 individuals
      with autism spectrum disorder (ASD) was compared to the rate in an anonymous
      consecutive birth cohort. RESULTS: The occurrence of inclusion positive slides
      was significantly greater in the ASD group compared to the control group (6/27
      slides, 22.2% vs. 12/154, 7.8%; Fisher Exact Test, two-tailed p = .033; relative
      risk 2.85). The proportion of positive cases was also greater in the ASD group
      (5/13 cases, 38.5% vs. 8/61, 13.1%; Fisher Exact, two-tailed p = .044; relative
      risk 2.93). Behavioral severity scores did not differ across groups of inclusion
      positive (N = 4) and negative (N = 8) ASD individuals. CONCLUSIONS: Although
      probably not functionally detrimental or causative, the greater occurrence of
      placental trophoblast inclusions observed in ASD individuals may reflect altered
      early developmental processes. Further research is required to replicate the
      basic finding, to understand the basis for the trophoblastic abnormality, and to
      determine the utility of the measure in early detection of ASD.

PMID- 16806107
TI  - Acute stress reduces reward responsiveness: implications for depression.
AB  - BACKGROUND: Stress, one of the strongest risk factors for depression, has been
      linked to "anhedonic" behavior and dysfunctional reward-related neural circuitry
      in preclinical models. METHODS: To test if acute stress reduces reward
      responsiveness (i.e., the ability to modulate behavior as a function of past
      reward), a signal-detection task coupled with a differential reinforcement
      schedule was utilized. Eighty female participants completed the task under both a
      stress condition, either threat-of-shock (n = 38) or negative performance
      feedback (n = 42), and a no-stress condition. RESULTS: Stress increased negative
      affect and anxiety. As hypothesized based on preclinical findings, stress,
      particularly the threat-of-shock condition, impaired reward responsiveness.
      Regression analyses indicate that self-report measures of anhedonia predicted
      stress-induced hedonic deficits even after controlling for anxiety symptoms.
      CONCLUSIONS: These findings indicate that acute stress reduces reward
      responsiveness, particularly in individuals with anhedonic symptoms. Stress
      induced hedonic deficit is a promising candidate mechanism linking stressful
      experiences to depression.

PMID- 16806108
TI  - Further evidence of association of OPRD1 & HTR1D polymorphisms with
      susceptibility to anorexia nervosa.
AB  - BACKGROUND: A recent study reported strong evidence for the involvement of a
      region on human chromosome 1 and genetic susceptibility to anorexia nervosa (AN).
      A more detailed analysis of this region has suggested 2 genes that may account
      for this susceptibility. These data suggest that polymorphisms in both the
      serotonin 1D (HTR1D) and opioid delta 1 (OPRD1) receptor genes show a significant
      association with restricting AN (RAN). METHODS: In the current study, we have
      conducted an independent association study on 226 females meeting DSM-IV criteria
      for AN and 678 matched volunteers. RESULTS: We genotyped 4 SNPs in HTR1D and 6
      SNPs in OPRD1. 3 SNPs were found to be associated with both RAN and binge-purge
      AN (BPAN) within the gene for OPRD1. We also found evidence of association
      between 2 polymorphisms within HTR1D and RAN. CONCLUSIONS: These data support the
      hypothesis that polymorphisms within this region form a component of the genetic
      basis to susceptibility to RAN. However, further work is required to understand
      the processes that may be mediated by these genes.

PMID- 16806109
TI  - Ameliorative effect of pioglitazone on seizure responses in genetically epilepsy
      susceptible EL mice.
AB  - Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, delayed
      the development of seizure responses and mildly shortened the duration of
      convulsion of genetically epileptic EL mice. mRNA levels of IL-1beta, IL-6 and
      TNF-alpha before seizure and mRNA levels of IL-6 and TNF-alpha after seizure were
      decreased in the brains of the mice with pioglitazone. These results suggest that
      pioglitazone may have ameliorative effects on epileptic seizure responses partly
      through the reduction of inflammatory responses in the brain.

PMID- 16806110
TI  - Assessment of CMV, RSV and SYN1 promoters and the woodchuck post-transcriptional
      regulatory element in adenovirus vectors for transgene expression in cortical
      neuronal cultures.
AB  - In order to investigate protein function in rat primary cortical neuronal
      cultures, we modified an adenoviral vector expression system and assessed the
      strength and specificity of the cytomegalovirus (CMV), rous sarcoma virus (RSV),
      and rat and human synapsin 1 (SYN1) promoters to drive DsRed-X expression. We
      also incorporated the woodchuck post-transcriptional regulatory element (WPRE)
      and a CMV promoter-enhanced green fluorescent protein (EGFP) reporter cassette.
      We observed that the RSV promoter activity was strong in neurons and moderate in
      astrocytes, while the CMV promoter activity was weak-to-moderate in neurons and
      very strong in astrocytes. The rat and human SYN1 promoters exhibited similar but
      weak activity in neurons, despite inclusion of the WPRE. We confirmed that the
      WPRE enhanced RSV promoter-mediated DsRed-X expression in a time-dependent
      fashion. Interestingly, we observed very weak SYN1-mediated DsRed-X expression in
      astrocytes and HEK293 cells suggesting incomplete neuronal-restrictive behavior
      for this promoter. Finally, using our adenoviral expression system, we
      demonstrated that RSV promoter-mediated Bcl-X(L) overexpression attenuated
      neuronal death caused by in vitro ischemia and oxidative stress.

PMID- 16806112
TI  - Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR
      mice.
AB  - Radix Angelica sinensis, known as Danggui in Chinese, has been used to treat
      cardiovascular and cerebrovascular diseases in Traditional Chinese Medicine for a
      long time. Modern phytochemical studies showed that Z-ligustilide (LIG) is the
      main lipophilic component of Danggui. In this study, we examined whether LIG
      could protect ischemia/reperfusion-induced brain injury by minimizing oxidative
      stress and anti-apoptosis. Transient forebrain cerebral ischemia (FCI) was
      induced by the bilateral common carotid arteries occlusion for 30 min. LIG was
      intraperitoneally injected to ICR mice at the beginning of reperfusion. As
      determined via 2,3,5-triphenyl tetrazolium chloride (TTC) staining at 24 h
      following ischemia, the infarction volume in the FCI mice treated without LIG
      (22.1 +/- 2.6%) was significantly higher than that in the FCI mice treated with 5
      mg/kg (11.8 +/- 5.2%) and 20 mg/kg (2.60 +/- 1.5%) LIG (P < 0.05 or P < 0.01).
      LIG treatment significantly decreased the level of malondialdehyde (MDA) and
      increased the activities of the antioxidant enzyme glutathione peroxidase (GSH
      PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P < 0.05 or P <
      0.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2
      expression as well as a significant decrease in Bax and caspase-3
      immunoreactivities in the ischemic cortex. The findings demonstrated that LIG
      could significantly protect the brain from damage induced by transient forebrain
      cerebral ischemia. The antioxidant and anti-apoptotic properties of LIG may
      contribute to the neuroprotective potential of LIG in cerebral ischemic damage.

PMID- 16806111
TI  - Gypenosides protect primary cultures of rat cortical cells against oxidative
      neurotoxicity.
AB  - Gypenosides (GPs) were tested for their ability to protect primary cultures of
      immature cortical cells against oxidative glutamate toxicity. In immature neural
      cells, glutamate cytotoxicity is known to be mediated by the inhibition of
      cystine uptake, leading to depletion of intracellular glutathione (GSH). The
      depletion of GSH impairs cellular antioxidant defenses resulting in oxidative
      stress and cell death. We found that pretreatment with GPs (100-400 microg/ml)
      significantly protected cells from glutamate-induced cell death. It was therefore
      of interest to investigate whether GPs protect cortical cells against glutamate
      induced oxidative injury through preventing GSH depletion. Results show that GPs
      significantly up-regulated mRNAs encoding gamma-glutamylcysteine synthetase
      (gamma-GCS) and glutathione reductase (GR) and enhanced their activities for GSH
      synthesis as well as recycle. Furthermore, GPs lowered the consumption of GSH
      through decreased accumulation of intracellular peroxides, leading to an increase
      in the intracellular GSH content. GPs were also found to prevent lipid
      peroxidation and reduce the influx of Ca(2+) which routinely follows glutamate
      oxidative challenge. GPs treatment significantly blocked glutamate-induced
      decrease in levels of Bcl-2 and increase in Bax, leading to a decrease in
      glutamate-induced apoptosis. Thus, we conclude that GPs protect cortical cells by
      multiple antioxidative actions via enhancing intracellular GSH, suppressing
      glutamate-induced cytosolic Ca(2+) elevation and blocking glutamate-induced
      apoptosis. The novel role of GPs implies their remarkable preventative and
      therapeutic potential in treatment of neurological diseases involving glutamate
      and oxidative stress.

PMID- 16806113
TI  - Differential expression of mouse orexin receptor type-2 (OX2R) variants in the
      mouse brain.
AB  - We have identified two novel mouse orexin type-2 receptor (OX2R) splice variants:
      OX2alphaR and OX2betaR. Here, we have mapped in detail the differential gene
      expression of OX2alphaR and OX2betaR in the mouse brain. Using RT-PCR and in situ
      hybridization, we show that OX2alphaR is expressed in various areas of the mouse
      brain and has low expression in caudal part of cerebellum. OX2betaR is expressed
      in detectable levels, with the exception of striatum, midbrain and anterior part
      of cerebellum/pons. Our novel findings demonstrate the differential expression of
      OX2R splice variants in the mouse brain.

PMID- 16806114
TI  - Substance P induces expression of the corticotropin-releasing factor receptor 1
      by activation of the neurokinin-1 receptor.
AB  - The neuropeptide substance P (SP) has been found to be possibly involved in the
      etiology of affective and anxiety disorders. However, the molecular mechanisms
      underlying this involvement are still poorly understood. In this study, we used
      macroarrays to investigate the differential gene expression profile induced by
      SP, particularly of genes which have been shown to be involved in the
      pathophysiology of affective disorders. As a model system, we used the human
      astrocytoma cell line U373 MG as well as primary rat astroglial cells, which both
      are known to express functional neurokinin-1 receptors (NK-1-R) and to secret
      various cytokines upon stimulation with SP. Among several regulated genes, we
      found that SP (100 and 1000 nM) induced the expression of the corticotropin
      releasing factor receptor 1 (CRF1 receptor). Further analyses revealed that this
      induction was mediated (a) via NK-1-R, as the selective NK-1-R-antagonist L
      733,060 (1 microM) strongly inhibited SP-induced CRF1 receptor expression, and
      (b) intracellularly, by protein kinase C, p42/44 and p38 mitogen-activated
      protein kinases (MAPK), as shown by using specific inhibitors of signal
      transduction pathways. In conclusion, this study demonstrates that SP induces
      CRF1 receptor expression in cells of the CNS, which may be of potential interest
      for a better understanding of the interplay between SP and the stress hormone
      axis and, thus, diseases like affective or anxiety disorders. Further studies are
      needed to substantiate this link in vivo.

PMID- 16806115
TI  - Enhancement of tyrosine hydroxylase expression and activity by Trypanosoma cruzi
      parasite-derived neurotrophic factor.
AB  - A parasite-derived protein, PDNF, produced by the Chagas' disease agent
      Trypanosoma cruzi, functionally mimics mammalian neurotrophic factors by delaying
      apoptotic death and promoting survival and differentiation of neurons, including
      dopaminergic cells, through the activation of nerve growth factor receptor TrkA.
      Because it is well established that neurotrophic factors regulate enzymes
      involved in the biosynthesis of neurotransmitters, we examined whether PDNF could
      also directly activate tyrosine hydroxylase (TH), a rate-limiting enzyme in the
      synthesis of dopamine and other catecholamine neurotransmitters. We found that
      primary cultures of rat ventral mesencephalon responded to PDNF by increasing the
      number of TH-positive neurons and, most importantly, preserved expression of TH
      in neurons treated with Parkinson disease-inducing neurotoxin 1-methyl-4-phenyl
      pyridinium (MPP(+)). In dopaminergic PC12 cells, PDNF induced TH transcription
      via CRE element in TH promoter followed by significant increase in TH protein and
      expansion of TH-positive cell population. Furthermore, PDNF stimulated TH
      enzymatic activity by enhancing phosphorylation of seryl residues 31 and 40
      through the activation of MAPK/Erk1/2 and cAMP-dependent protein kinase A
      signaling, respectively. Therefore, our results indicate that PDNF, in addition
      to its functioning as survival and differentiation-promoting factor for
      dopaminergic neuronal cells, can directly influence activity of the rate-limiting
      enzyme that underlies catecholamine biosynthetic cascade. This novel feature of
      PDNF should help understand the mechanism of neuronal function altered by T.
      cruzi infection, specifically neurotransmitter secretion. In addition, the
      findings have potential implications in the therapy of Chagas' and other
      neurodegenerative disorders.

PMID- 16806116
TI  - In vivo imaging of apoptosis in patients with acute stroke: correlation with
      blood-brain barrier permeability.
AB  - BACKGROUND: We wished to determine the ability of radiolabeled annexin V to
      concentrate at sites of ischemic injury in patients with acute cerebral stroke.
      Secondly, we sought to correlate annexin V imaging in these patients with the
      degree of blood-brain barrier (BBB) breakdown. METHODS: Twelve patients with
      acute stroke had a complete neurological examination, including the National
      Institutes of Health (NIH) stroke scale and the Glasgow Coma Score (GCS). A non
      contrast CT scan was performed on all patients. A SPECT of the brain was obtained
      2 h after injection of annexin V. The integrity of the BBB was evaluated in seven
      patients using Tc-99m-DTPA brain SPECT. RESULTS: All patients had an infarct in
      the MCA territory. Eight patients had abnormal increased annexin V activity,
      which was more common in patients with cortical strokes (P = 0.01). The
      concentration of annexin had no correlation to the volume of stroke, but it was
      significantly and inversely related to the GCS on admission (r = -0.7, P = 0.02).
      Foci of apoptosis were noted contralateral to the affected hemisphere as well.
      All seven patients who underwent DTPA SPECT showed breakdown of the BBB. DTPA
      uptake was significantly and positively associated with NIH score (r = 0.80, P =
      0.01) and inversely associated with GCS (r = -0.89, P = -0.03). CONCLUSION: This
      study shows that it is possible to identify in vivo regions of ischemic neuronal
      injury using radiolabeled annexin V in patients with acute stroke. Annexin
      imaging can play a major role in the selection of therapy in the initial period
      following stroke in adults.

PMID- 16806117
TI  - Neurogenesis of oxytocin-containing neurons in the paraventricular nucleus (PVN)
      of the female pig in 3 reproductive states: puberty gilts, adult gilts and
      lactating sows.
AB  - Evidence suggests that neurogenesis occurs in the adult hypothalamus, including
      centers containing oxytocin and vasopressin producing neurons. The present study
      was undertaken to look at one of these centers, the paraventricular nucleus
      (PVN), to describe its morphology, confirm the presence of neurogenesis and
      examine the effect of reproductive status on the incidence of neurogenesis.
      Serial sections of the paraffin-embedded hypothalamus were made from five puberty
      gilts, four adult gilts and four lactating sows. Specific sections were Nissl
      stained for PVN morphology, while others were stained with an oxytocin (OT)
      primary antibody, which binds to the cytoplasm of oxytocin-containing neurons,
      and proliferating cell nuclear antigen (PCNA) primary antibody, which binds to
      PCNA, a protein expressed in the nucleus during cell division. Cells labeled with
      both OT and PCNA were considered to be oxytocin-containing neurons that had
      recently divided, signifying the recent synthesis of a mature neuron. The general
      morphology of the PVN was similar in all pigs, and three subnuclei were
      identified and named based on cytoarchitecture. Neurogenesis was consistently
      observed in OT-containing neurons of all pigs studied. However, a significantly
      greater number of double-labeled (OT + PCNA) cells occurred in the PVN of
      lactating sows and adult gilts, when compared to puberty gilts. These
      observations confirm the process of neurogenesis in the hypothalamus of the adult
      female pig and suggest that the up-regulation of OT-containing neurons is
      correlated to age and possibly driven by sexual maturation, but not necessarily
      lactation.

PMID- 16806119
TI  - Developmental changes in the vascular network of the rat visual areas 17, 18 and
      18a.
AB  - The present study examines quantitatively the areal and the laminar fluctuations
      of the vascular network in the visual areas 17, 18 and 18a of the rat cerebral
      cortex, from postnatal day (P) 1 to P60. For this purpose, the detailed vascular
      networks of the visual areas, marked after transcardial perfusion of India ink,
      are analyzed with the use of an image analysis system in order to measure the
      total vascular density (VD) and the relative density of capillaries (CD), of
      medium (MD)- and large (LD)-sized vessels in combination with changes in the mean
      diameter of all three types of vessels. Comparative quantitative microscopy
      showed that both VD and CD do not exhibit significant interareal differences in
      the adult rat brain. However, while VD reaches adult values much earlier in area
      18a (P21) than in areas 17 and 18 (P60), CD obtains adult values at P31 in areas
      17 and 18a, but later (P60) in area 18. Maturation process of laminar VD, CD, MD
      and LD was not found to follow a simple (i.e. inside-out or mediolateral)
      sequence, and, in each cortical area, laminar fluctuations of vessels density
      revealed a complicated developmental pattern, which might be attributed to their
      changing structural and functional status. Developmental changes in the diameter
      of capillaries, examined in conjunction with concomitant changes of vascular and
      capillary density in each area, suggest the existence of angiogenesis in all
      three visual areas during the third postnatal week of age.

PMID- 16806118
TI  - Fast cholinergic efferent inhibition in guinea pig outer hair cells.
AB  - Hair cells of inner ear are suggested to be inhibited by the activation of the
      alpha9-containing nicotinic acetylcholine (ACh) receptors (alpha9-containing
      nAChRs). Several studies have suggested that the native nicotinic-like ACh
      receptors (nAChRs) in hair cells display a significant permeability of Ca(2+)
      ions and unusual pharmacological properties. The activation of native nAChRs will
      initiate the hyperpolarization of hair cells by activation of the small
      conductance, Ca(2+)-activated K(+) channels (SK). In this work, the properties of
      the ACh-sensitive potassium current (IK(ACh)) in outer hair cells (OHCs) of
      guinea pigs were investigated by employing whole-cell patch-clamp. Followed by
      perfusion of ACh, OHCs displayed a rapid desensitized current with an N-shaped
      current-voltage curve (I-V) and a reversal potential of - 66 +/- 7 mV. The
      IK(ACh) was still present during perfusion of either iberiotoxin (IBTX, 200 nM)
      or TEA (5 mM) but was potently inhibited by apamin (1 muM), TEA (30 mM). The
      IK(ACh) demonstrated a strong sensitivity to alpha-bungarotoxin (alpha-BgTx),
      bicuculline and strychnine. These results suggested that OHCs display the well
      known SK current, which might be gated by the alpha9-containing nAChRs. Two
      important changes were present after lowering the Ca(2+) concentration in the
      external conditions from 2 mM to 0.2 mM: one was a flattened N-shape I-V
      relationship with a maximum shifted toward hyperpolarized potentials from -20
      approximately -30 mV approximately -40 to -50 mV, the other was a significant
      reduction in the agonist maximal response (percentage of maximal response 10.5 +/
      5.4). These results indicated that native nAChRs are both permeable to and
      modulated by extracellular Ca(2+) ions. Taken together, this work provides direct
      evidences that SK channels in OHCs of guinea pigs are gated by alpha9-containing
      nAChRs, which play an important role in the fast cholinergic efferent inhibition.
      This fast inhibition is both potently dependent on the permeability of Ca(2+)
      ions through the native nAChRs and modulated by Ca(2+) ions.

PMID- 16806120
TI  - Cytosolic prostaglandin E2 synthase (cPGES) expression is decreased in discrete
      cortical regions in psychiatric disease.
AB  - The number of adults in the US affected by bipolar disorder, depression, or
      schizophrenia is approaching 15 million. Despite decades of research, etiologies
      of these illnesses remain elusive. Theories of aberrant brain morphology,
      neurotransmission, and signal conduction have provided the heuristic framework
      for a large body of literature, with attention focused upon hypotheses of
      monoamine signaling underlying psychiatric disease. More recently, attention has
      turned to potential contributions of other signaling pathways, including the
      arachidonic acid cascade and generation of prostaglandins (PG). To determine the
      potential involvement of the pathways leading to PGE2 synthesis in psychiatric
      disease, immunohistochemistry and immunoblotting were performed to measure
      regional expression of the cyclooxygenases (COX) and one of the terminal PGE2
      synthases (PGES) in postmortem tissue provided by The Stanley Medical Research
      Institute. For normal, bipolar, depressed, and schizophrenic subjects, COX-1 and
      COX-2 protein levels did not differ across region and patient populations. In
      contrast, there was a significant effect of diagnosis on cytosolic PGES (cPGES)
      protein levels in the frontal cortex, with remarkable decreases observed in all
      psychiatric groups relative to normal tissue (P < 0.05). Significant reduction of
      cPGES expression was also found in the temporal cortex of bipolar subjects.
      Evaluation of medicated vs. non-medicated subjects revealed a significant effect
      of medication on cPGES expression in the frontal cortex of bipolar, but not
      depressed or schizophrenic subjects. These novel findings further support
      hypotheses of abnormalities in fatty acid and phospholipid metabolism in regions
      associated with psychiatric disease.

PMID- 16806121
TI  - Serotonergic modulation of synaptic transmission and action potential firing in
      frog motoneurons.
AB  - Frog spinal neurons receive a prominent innervation from the bulbar serotonergic
      nuclear complex. We used an isolated spinal cord preparation to examine the
      effect of serotonin (5-hydroxytryptamine, 5-HT) receptor activation on segmental
      and descending monosynaptic excitatory inputs to frog lumbar motoneurons. Bath
      application of 5-HT (0.05 mM) caused a significant reduction in the peak
      amplitude of segmental EPSP elicited by dorsal root (DR) stimulation (P < 0.05).
      Contrasting to DR evoked responses 5-HT did not affect the descending
      monosynaptic EPSP conditioned by ventrolateral column (VLC) stimulation.
      Recording of the VLC induced EPSP-spike (E-S) field response within the ventral
      horn motor nucleus disclosed a substantial enhancement in the population
      discharge of motoneurons upon 5-HT application (P < 0.05). These data suggest the
      potential importance of serotonergic receptors in motor integration and gaining
      of motor output in the frog spinal cord.

PMID- 16806122
TI  - Ethanol modifies the effect of handling stress on gene expression: problems in
      the analysis of two-way gene expression studies in mouse brain.
AB  - Studies analysing the effects of acute treatments on animal behaviour and brain
      biochemistry frequently use pairwise comparisons between sham-treated and 
      untreated animals. In this study, we analyse expression of tPA, Grik2, Smarca2
      and the transcription factor, Sp1, in mouse cerebellum following acute ethanol
      treatment. Expression is compared to saline-injected and -untreated control
      animals. We demonstrate that acute i.p. injection of saline may alter gene
      expression in a gene-specific manner and that ethanol may modify the effects of
      sham treatment on gene expression, as well as inducing specific effects
      independent of any handling related stress. In addition to demonstrating the
      complexity of gene expression in response to physical and environmental stress,
      this work raises questions on the interpretation and validity of studies relying
      on pairwise comparisons.

PMID- 16806123
TI  - Sexual dimorphism in the vomeronasal system of the rabbit.
AB  - Studies have shown that the vomeronasal system (VNS), an olfactory neural network
      that participates in the control of reproductive physiology and behavior, is
      sexually dimorphic in the rat. These works have also shown two main
      characteristics of brain sexual dimorphism: (a) dimorphism appears in neural
      networks related to reproduction and (b) it can present two morphological
      patterns: one in which males present greater morphological measures than females
      (male > female) and another in which the opposite is true (female > male). The
      present work extends the hypothesis to the rabbit, as a representative species of
      Lagomorpha. In addition, the locus coeruleus (LC), which is known to send rich
      noradrenergic projections to VNS structures, was also studied. Sex differences
      were found in: (a) the number of mitral, and dark and light granule cells (female
      > male) of the accessory olfactory bulb (AOB); (b) the medial amygdala (Me) and
      its dorsal (Med) and ventral (Mev) subdivisions, males showing greater values
      than females in volume and number of neurons, while in the posteromedial cortical
      amygdala (PMCo or C(3)), females show greater density of neurons than males and
      (c) the posteromedial division of the bed nucleus of the stria terminalis (BSTMP)
      in which males have more neurons than females. No sex differences were seen in
      the bed nucleus of the accessory olfactory tract (BAOT) and the LC. These results
      evidence that, as it was observed in rodents, sex differences are also seen in
      the VNS of Lagomorpha and that these sex differences present the two
      morphological patterns seen in Rodentia. Differences between orders are discussed
      with respect to the species-specific physiological and behavioral peculiarities.

PMID- 16806124
TI  - Control of dopamine-secretion by Tet-Off system in an in vivo model of
      parkinsonian rat.
AB  - We established a PC12 cell line (PC12TH Tet-Off) in which human tyrosine
      hydroxylase (TH) expression can be negatively controlled by Doxycycline (Dox).
      First, dopamine (DA)-secretion from PC12TH Tet-Off cells was controlled by Dox
      administration in a dose-responsive manner ranging from 0 to 100 ng/ml for 70
      days in vitro. Furthermore, Parkinson's disease model of rats receiving
      encapsulated PC12TH Tet-Off cells displayed a significant decrease of dopamine
      concentration in the cerebrospinal fluid (CSF) and increase of the number of
      apomorphine-induced rotations by Dox-administration, as compared to transplanted
      rats without Dox-administration, although the significant decrease of the
      reduction ratio of DA concentration in the CSF with Dox-administration was
      recognized over time. At 2 months post-implantation, concentration of dopamine in
      the implanted striatum and from the retrieved capsules demonstrated that the
      control of DA-secretion could be partially achieved for 2 months in vivo. Our
      results support both the value of cell therapy using Tet-Off system and the
      technique of encapsulation might be a feasible option for Parkinson's disease
      especially in resolving the problem of dopamine oversupply in the future,
      although a more efficient way to control DA-secretion with quicker regulation and
      much titration of dose should be explored before clinical application.

PMID- 16806125
TI  - Immunohistochemical study of caveolin-1 in the sciatic nerves of Lewis rats with
      experimental autoimmune neuritis.
AB  - The expression of caveolin-1 and the related molecule endothelial nitric oxide
      synthase (eNOS) was analyzed in the sciatic nerves of Lewis rats with
      experimental autoimmune neuritis (EAN). Western blot analysis showed that
      caveolin-1 significantly increased in the sciatic nerves with EAN upon initiation
      of cell infiltration during the early and peak stages (days 10 and 14 post
      immunization, p.i.) and declined thereafter. The pattern of eNOS expression over
      the course of EAN largely matched that of caveolin-1. Immunohistochemistry showed
      that in EAN lesions, intense caveolin-1 immunostaining occurred in ED1-positive
      macrophages as well as in vessels, while the caveolin-1 immunoreaction was
      reduced in Schwann cells in the inflammatory lesions. Consequently, we postulated
      that caveolin-1 expression increased in the sciatic nerves with EAN; this
      possibly mediated either molecular trafficking or nitric oxide generation partly
      through the activation of eNOS in vascular endothelial cells, as well as in
      inflammatory macrophages in EAN and/or cellular apoptosis of inflammatory cells.

PMID- 16806126
TI  - Vibrotactile adaptation enhances spatial localization.
AB  - A two-interval forced choice tracking procedure was used to evaluate the effects
      of a pre-exposure to vibrotactile stimulation ("adaptation") on the capacity of
      human subjects to spatially localize a subsequent tactile stimulus. A 25 Hz
      flutter adapting stimulus was presented at a randomly selected position within a
      20 mm linear array oriented transversely on the hand dorsum. Two flutter stimuli
      delivered subsequently were applied to different sites along the linear array;
      one to the same locus that received the adapting stimulation (the "standard"
      stimulus), the other to a distant site (the "test" stimulus). Following each
      trial, subjects were queried as to which of the two stimuli was delivered to the
      same skin site that received adapting stimulation. A correct response resulted in
      a reduced distance between the sites contacted by the standard and test stimuli
      in the following trial. Four subjects participated in 10 sessions each. A session
      consisted of two sets of 20 trials (one set at 0.5 s and another at 5 s adapting
      stimulus duration). For every subject, 5 s adaptation resulted in an
      approximately 2-fold improvement in spatial discrimination performance over that
      achieved following 0.5 s adaptation. It is proposed that the improved human
      vibrotactile spatial localization performance following 5 s of 25 Hz stimulation
      is due to enhanced spatial funneling of the global neuronal population response
      of primary somatosensory cortex (SI) that has been demonstrated to accompany
      increases in duration of 25 Hz flutter stimuli delivered to the skin.

PMID- 16806127
TI  - Microwave-promoted hydrolysis of plant seed gums on alumina support.
AB  - Using a catalytic amount of potassium persulfate (1.48 x 10(-4)M), eight
      different seed gums were fully hydrolyzed on alumina support under microwave
      irradiation. The hydrolysis time varied between 1.33 and 2.33 min depending upon
      the seed gum structure. The used solid support could be easily separated from the
      hydrolyzates and recycled. However, under microwave field in an aqueous medium,
      the same amount of persulfate was unable to hydrolyze the seed gums. Solid
      supported microwave hydrolysis has been compared with the microwave-enhanced
      aqueous hydrolysis (using K2S2O8 or 0.1N H2SO4) and also with the conventional
      hydrolysis procedures.

PMID- 16806128
TI  - Docking studies on glycoside hydrolase Family 47 endoplasmic reticulum alpha-(1-
      >2)-mannosidase I to elucidate the pathway to the substrate transition state.
AB  - Alpha-(1-->2)-mannosidase I from the endoplasmic reticulum (ERManI), a Family 47
      glycoside hydrolase, is a key enzyme in the N-glycan synthesis pathway. Catalytic
      domain crystal structures of yeast and human ERMan1s have been determined, the
      former with a hydrolytic product and the latter without ligands, with the
      inhibitors 1-deoxymannojirimycin and kifunensine, and with a thiodisaccharide
      substrate analog. Both inhibitors were bound at the base of the funnel-shaped
      active site as the unusual 1C4 conformer, while the substrate analog glycon is a
      3S1 conformer. In the current study, AutoDock was used to dock alpha-D
      mannopyranosyl-(1-->2)-alpha-D-mannopyranose with its glycon in chair (1C4,4C1),
      half-chair (3H2,3H4,4H3), skew-boat (OS2,3S1,5S1), boat (2,5B,3,OB,B1,4,B2,5),
      and envelope (3E,4E,E3,E4) conformations into the yeast ERManI active site. Both
      docked energies and forces on docked ligand atoms were calculated to determine
      how the ligand distorts to the transition state. From these, we can conclude that
      (1) both 1C4 and OS2 can be the starting conformers; (2) the most likely binding
      pathway is 1C4-->3H2-->OS2-->3,OB-->3S1-->3E; (3) the transition state is likely
      to be close to a 3E conformation.

PMID- 16806129
TI  - Physicochemical properties and antitumor activities of water-soluble native and
      sulfated hyperbranched mushroom polysaccharides.
AB  - A water-soluble hyperbranched beta-glucan, coded as TM3b, extracted from
      sclerotia of an edible fungus (Pleurotus tuber-regium) was fractioned into eight
      fractions coded as F1-F8 by a nonsolvent addition method. Five fractions were
      treated with chlorosulfonic acid at 35 degrees C to synthesize successfully
      sulfated derivatives coded as S-F2, S-F3, S-F4, S-F5, and S-F8 with degree of
      substitution of 0.28-0.54. The 13C NMR results of these sulfated beta-glucans
      indicated that while the C-6 position was fully substituted, C-2, C-3, and C-4
      were only partially substituted by the sulfate groups. The weight-average
      molecular weights (Mw) and intrinsic viscosities ([eta]) of the native and
      sulfated TM3b fractions were determined using multi-angle laser light scattering
      and viscometry in 0.15M aq NaCl at 25 degrees C, respectively. The dependences of
      [eta] on Mw for TM3b and sulfated TM3b were found to be [eta]=0.18Mw(0.28+/-0.03)
      (Mw range from 3.30 x 10(4) to 3.90 x 10(7)) and [eta]=2.24 x 10(-2)Mw(0.52+/
      0.06) (Mw range from 3.24 x 10(4) to 3.15 x 10(5)) in 0.15M aq NaCl at 25 degrees
      C, respectively. It revealed that both the native TM3b and its sulfated
      derivatives exist in a spherical chain conformation in 0.15M aq NaCl.
      Furthermore, the native and sulfated TM3b fractions showed potent antitumor
      activities in vivo and in vitro. The sulfated derivatives exhibited relatively
      higher in vitro antitumor activity against human hepatic cancer cell line HepG2
      than the native TM3b. Water solubility and introduction of sulfate groups were
      the main factors in enhancing the antitumor activities.

PMID- 16806130
TI  - Facile and regioselective preparation of partly O-benzylated D-glucopyranose
      acetates via acid-mediated simultaneous debenzylation-acetolysis.
AB  - Fully O-benzylated methyl alpha-D-glucopyranoside shows a steady order in
      stepwise debenzylation when it is treated with sulfuric acid in acetic anhydride.
      Based on the order of debenzylation, regioselective preparations of 2,3,4-tri-,
      2,3-, 2,4-, 3,4-di-, and 2-O-benzyl-D-glucopyranose acetates were facilitated in
      greater than 80% yields. The key points of the preparative reactions were the
      control of the acid strength and choice of suitable substrates.

PMID- 16806131
TI  - New conformationally locked thioderivatives of mannose: synthesis, applications,
      and mechanistic studies.
AB  - Tetrathiomolybdate has been used as an efficient sulfur-transfer reagent in the
      synthesis of a number of thiolevomannosan derivatives having an axial-rich 1C4
      conformation. An unprecedented synthesis of a novel thioorthoester and its
      synthetic utility in glycosylation has been demonstrated. This is a general and
      efficient method for the synthesis of conformationally locked thiosugars.

PMID- 16806132
TI  - Enzymatic synthesis of aldonic acids.
AB  - Several aldonic acids (D-mannonic, D-galactonic, D-xylonic, 2-deoxy-D
      arabinohexonic (2-deoxy-D-gluconic)) were prepared on a scale of several grams by
      a simple oxidation catalyzed by glucose oxidase in pure water.

PMID- 16806133
TI  - Virus receptor trap neutralizes coxsackievirus in experimental murine viral
      myocarditis.
AB  - OBJECTIVE: The coxsackie and adenovirus receptor (CAR) and the decay-accelerating
      factor (DAF) are receptors for coxsackievirus B3 (CVB3), which is known as the
      major cause of human viral myocarditis. We investigated the potential for
      therapeutic use of soluble virus receptor fusion proteins. METHODS: We designed
      and generated a novel virus receptor trap (hCAR-hDAF:Fc) consisting of both CVB3
      receptors and the Fc portion of human IgG1 and evaluated its antiviral effects in
      experimental CVB3 myocarditis. RESULTS: Among four soluble virus receptor fusion
      proteins (hCAR:Fc, hDAF:Fc, hCAR-hDAF:Fc and hDAF-hCAR:Fc), hCAR:Fc and hCAR
      hDAF:Fc in the supernatant of transfected cells neutralized echovirus,
      adenovirus, and various serotypes of CVB in a dose-dependent manner. Both soluble
      viral receptor proteins bound to the VP0 and VP1 capsid proteins of CVB3. The in
      vivo efficacy of viral receptor proteins was evaluated by intramuscular injection
      of plasmid (hCAR:Fc or hCAR-hDAF:Fc) followed by electroporation in a murine
      model of CVB3 myocarditis. Serum levels of the virus receptor proteins increased
      relative to baseline values from day 3 and peaked on day 14 at 12.9-fold for
      hCAR:Fc and 7.1-fold for hCAR-hDAF:Fc. The 3-week survival rate was significantly
      higher in hCAR-hDAF:Fc-treated mice (61%) than in hCAR:Fc-treated mice (29%) and
      in controls (15%; p<0.05). Myocardial inflammation, fibrosis, and myocardial
      virus titers were all significantly reduced in the hCAR:Fc and hCAR-hDAF:Fc
      groups compared to the controls. CONCLUSION: Our soluble virus receptor trap,
      hCAR-hDAF:Fc, attenuated viral infection, myocardial inflammation, and fibrosis,
      resulting in higher survival rates in mice with coxsackieviral myocarditis.
      Furthermore, it consists exclusively of human components, and we demonstrated
      that this soluble virus receptor trap may be used as a potential candidate for a
      novel therapeutic agent for the treatment of acute viral myocarditis during the
      viremic phase.

PMID- 16806134
TI  - RETRACTED: Si RNA inhibition of GRP58 associated with decrease in mitomycin C
      induced DNA cross-linking and cytotoxicity.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (https://www.elsevier.com/about/our-business/policies/article-withdrawal).This
      article has been retracted at the request of the Office of Integrity of the
      University of Maryland due to data entered in Fig 3 of the publication that were
      not supported by raw data, in addition to the fact that the statistical
      evaluations were adultered.

PMID- 16806135
TI  - Identification of lipid binding and lipoprotein lipase activation domains of
      human apoAV.
AB  - ApoAV, a newly discovered apolipoprotein, plays a key role in human triglyceride
      homeostasis; however, the structure-function correlation of apoAV is not clearly
      understood. To explore the relationship, wild type and six deletion mutants, that
      is (AV (Delta(1-51)), AV (Delta(51-128)), AV (Delta(132-188)), AV (Delta(192
      238)), AV (Delta(246-299)), AV (Delta(301-343))), of human apoAV expressed in
      Escherichia coli were studied. All the deleted regions together encompass almost
      the entire 343 amino acid sequence of wild type apoAV. Circular dichroism
      spectroscopy showed that the alpha helical content of lipid-free wild type apoAV
      was 46%. In comparison with wild type apoAV, AV (Delta(192-238)) and AV
      (Delta(301-343)) displayed significantly decreased lipid binding activities,
      confirming the importance of these two regions in lipid binding function of
      apoAV. While, the LPL activation function of apoAV remarkably impaired after
      deletion of residues 192-238. These findings suggested that the domain (192-238)
      is absolutely necessary for apoAV in lipid binding and lipoprotein lipase
      activation.

PMID- 16806136
TI  - Effects of atorvastatin and apoA-I/phosphatidylcholine discs on triglyceride-rich
      lipoprotein subfractions as characterized by capillary isotachophoresis.
AB  - BACKGROUND: The present study examined the effects of atorvastatin and the in
      vitro effect of apolipoprotein (apo) A-I/phosphatidylcholine (POPC) discs on
      charge-based triglyceride-rich lipoprotein (TRL) subfractions in a patient with
      type III hyperlipoproteinemia (HLP) and the apoE2/2 phenotype. METHODS: Charge
      based lipoprotein subfractions were characterized by capillary isotachophoresis
      (cITP). cITP analysis was performed using plasma that had been prestained with a
      lipophilic dye on a Beckman P/ACE MDQ system. RESULTS: Treatment with
      atorvastatin for 4 weeks markedly decreased the slow (s)-migrating TRL
      subfraction and both fast- and slow-migrating low-density lipoprotein (LDL)
      subfractions, but did not affect the fast (f)-migrating TRL subfraction in this
      patient. ApoA-I/POPC discs consisted of two major charge-based subfractions that
      had the mobility of cITP fTRL and sTRL. Incubation of plasma from this patient in
      the presence of apoA-I/POPC discs caused not only a reduction in cITP fast- and
      intermediate-migrating HDL and an increase in cITP sHDL but also a reduction in
      fTRL and sTRL and an increase in sLDL. CONCLUSION: Atorvastatin and apoA-I/POPC
      discs decreased cITP TRL subfractions in a complementary manner, suggesting that
      the combination of apoA-I/POPC discs and atorvastatin could be a promising
      therapeutic approach for hypertriglyceridemia.

PMID- 16806137
TI  - Serum vitamin A and zinc levels of healthy people in northeast Thailand.
AB  - BACKGROUND: Vitamin A and zinc are micronutrients which co-related to diseases
      afflicting northeast Thais. Vitamin A and zinc concentrations in serum have been
      studied in healthy northeast Thais between 23 and 75 years. METHODS: Vitamin A
      was analyzed by HPLC and zinc was determined by flame atomic absorption
      spectrometry. RESULTS: The average serum vitamin A level of the population
      (n=744) was 2.30 micromol/l (95% CI=2.25-2.35). Males had significantly higher
      vitamin A levels than females, i.e. 2.61 micromol/l (95% CI=2.53-2.68) vs. 2.03
      micromol/l (95% CI=1.98-2.09) (p<0.0001). The vitamin A level of females tended
      to increase significantly with age (p<0.005), whereas in males levels were
      relatively constant throughout the age range studied. The average serum zinc
      level of the population (n=1113) was 18.20 micromol/l (95% CI=18.05-18.36). There
      was no significant difference in the zinc levels between males and females, i.e.
      18.20 micromol/l (95% CI=17.90-18.36) vs. 18.36 micromol/l (95% CI=18.05-18.66).
      The zinc level tended to decrease significantly as age increased, particularly in
      the male population (p<0.05). CONCLUSION: The results from this study provide
      baseline data of serum vitamin A and zinc levels in healthy northeast Thais.

PMID- 16806138
TI  - Mutational heterogeneity in low-density lipoprotein receptor gene related to
      familial hypercholesterolemia in Morocco.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder
      caused by mutations in the low-density lipoprotein receptor (LDLR),
      apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9)
      genes. Until now, molecular data concerning FH in Morocco is still limited. To
      gain more information in this field and to assess the contribution of these three
      genes in the cause of FH determinism, we analyzed six unrelated Moroccan probands
      and twenty-five of their family's members. METHODS: After LDLR and APOB genotype
      analysis, we screened the LDLR gene for mutations using southern blot and PCR
      sequencing analysis. We also screened the APOB gene for the two common mutations
      R3500Q and R3531C by PCR-mediated site-directed mutagenesis. The PCSK9 gene was
      analyzed by direct sequencing. RESULTS: We identified three novel mutations
      (C25X, IVS3+5G>T, D558A) and two mutations previously described (D151N, A480E) in
      the LDLR gene. The R3500Q and R3531C mutations are absent in our probands and for
      1 proband, the implication of LDLR, APOB and PCSK9 genes was excluded, supporting
      the implication of a fourth gene in the determination of FH. CONCLUSION: These
      data are in agreement with our previous study that suggests a heterogeneous
      mutational spectrum of FH in Morocco.

PMID- 16806139
TI  - Analysis of clinical manifestations, mutant gene and encoded protein in two
      Chinese MYH9-related disease families.
AB  - BACKGROUND: MYH9-related disease is a rare autosomal dominant disorder
      characterized by the triad of giant platelet, thrombocytopenia and inclusion
      bodies in neutrophil. In recent years, much progress has been made in the
      investigation of its clinical feature and pathogenesis. METHODS: Clinical
      manifestations were analyzed in two Chinese MYH9-related disease families.
      Polymerase chain reaction (PCR), DNA sequencing and CpoI restrictive endonuclease
      map analysis were used to identify spot mutation in nonmuscle myosin heavy chain
      9 (MYH9) gene. Indirect immunofluence combined propidium iodine (PI) nuclei count
      staining technology was applied to probe nonmuscle myosin heavy chain IIA (NMMHC
      A) in MYH9-related disease neutrophils and platelets. Western blot was undergone
      to examine the expression of NMMHC-A in MYH9-related disease patients. RESULTS:
      All of the patients manifested with the typical triad, mild to moderate bleeding
      tendency were their common clinical feature, some patients were accompanied by
      renal lesion. G5521A mutation in MYH9 gene was identified in both families.
      Spindle-like inclusions with yellow fluorescence in MYH9-related disease
      neutrophils were clearly revealed by indirect immunofluence combined PI nuclei
      count-staining technology, which matched very well with the inclusions, detected
      by Wright-Giemsa's stain. An upregulation of NMMHC-A in MYH9-related disease
      neutrophils was observed by Western blotting analysis. CONCLUSION: Mutation of
      MYH9 gene exists in cases of Chinese MYH9-related disease. In the two families,
      the point mutation was located in exon 38(G5521A), and the transference rule of
      the MYH9 gene mutation is corresponding with clinical phenotype distribution.
      Indirect immunofluorescence combining with PI nuclei staining technology is
      sensitive and more specific than Wright-Giemsa's staining in detecting MYH9
      related disease inclusions, with which we might easily distinguish MYH9-related
      disease inclusions from infection-associated inclusions. The expression of the
      NMMHC-A in MYH9-related disease neutrophils was upregulated than normal control.

PMID- 16806140
TI  - Evaluation of renal enzymuria and cellular excretion as an marker of acute
      nephrotoxicity due to an overdose of paracetamol in Wistar rats.
AB  - INTRODUCTION: The present study was conducted to determine whether the urinary
      levels of excreted enzymes, gamma-glutamyltransferase (GGT), alkaline phosphatase
      (ALP), lactate dehydrogenase (LDH), aspartate (AST) and alanine aminotransferases
      (ALT), can efficiently indicate, within 24 h, an acute nephrotoxicity due to an
      overdose of paracetamol (PAR). METHODS: A baseline urine was collected from the
      experimental group. Thereafter, blood collected from the orbital sinus (1.0 ml)
      and paracetamol (650 mg/kg of body weight) was administered by gavage. After the
      drug administration, animals were returned to the metabolic cages and then urine
      was collected in the next 22 h. Blood and urine collection was performed at time
      0+24 h (T(24)), as well as at times 48 and 72 h (T(48) and T(72)). After the last
      urine and blood collection, the rats were killed and the kidneys removed and
      prepared for histological examination. Plasma creatinine and urinary levels of
      creatinine (to determinate glomerular filtration rate-GFR), GGT, ALP, LDH, ALT
      and AST were measured. Kidney tissues were stained with hematoxylin and eosin
      stain for histological assessment. RESULTS: Urinary levels of GGT, ALP and LDH
      enzymes were significantly higher (P<0.05) at T(24) when compared to the levels
      at T(0) and returned to basal levels at T(48) and T(72). The number of urinary
      epithelial cells at T(24) was significantly higher when compared to the control
      time (T(0)) (P<0.001). The GFR was significantly reduced 24, 48 and 72 h after
      the drug administration. CONCLUSION: The number of urinary epithelial cells and
      urinary enzymes levels are a simple and low cost procedure that is available and
      can help in the detection of renal acute lesions.

PMID- 16806141
TI  - Mechanism of ascorbic acid interference in biochemical tests that use peroxide
      and peroxidase to generate chromophore.
AB  - BACKGROUND: Ascorbic acid interferes negatively in peroxidase-based tests
      (Trinder method). However, the precise mechanism remains unclear for tests that
      use peroxide, a phenolic compound and 4-aminophenazone (4-AP). We determined the
      chemical mechanism of this interference, by examining the effects of ascorbic
      acid in the reaction kinetics of the production and reduction of the oxidized
      chromophore in urate, cholesterol, triglyceride and glucose tests. Reaction of
      ascorbic acid with the Trinder method constituents was also verified. RESULTS:
      Ascorbic acid interfered stoichiometrically with all tests studied. However, it
      had two distinct effects on the reaction rate. In the urate test, ascorbic acid
      decreased the chromophore formation with no change in its production kinetics. In
      contrast, in cholesterol, triglyceride and glucose tests, an increase in the lag
      phase of color development occurred. Of all the Trinder constituents, only
      peroxide reverted the interference. In addition, ascorbic acid did not interfere
      with oxidase activity nor reduce significantly the chromophore formed.
      CONCLUSIONS: Peroxide depletion was the predominant chemical mechanism of
      ascorbic acid interference in the Trinder method with phenolics and 4-AP.
      Distinctive effects of ascorbic acid on the reaction kinetics of urate,
      cholesterol, glucose and triglyceride might be due to the rate of peroxide
      production by oxidases.

PMID- 16806142
TI  - Inclusion of MPA and in a rapid multi-drug LC-tandem mass spectrometric method
      for simultaneous determination of immunosuppressants.
AB  - BACKGROUND: [corrected] Mycophenolic Acid (MPA) is often co-prescribed as part of
      a multiple immunosuppressant drug regimen. In this study an established LC-MS/MS
      method for the measurement of immunosuppressants cyclosporine A, tacrolimus,
      sirolimus and everolimus was optimized to include MPA without changing the sample
      pre-treatment and the LC-MS/MS configuration. METHODS: The sample pretreatment
      for EDTA-plasma was used as for whole blood. After protein precipitation of 50
      mul EDTA-plasma fast on-line matrix clean-up was performed using a column
      switching program. The chromatographic step was optimized to separate MPA and its
      glucuronide metabolite (MPAG). Multiple reaction monitoring (MRM) was used for
      detection of MPA (337.7>207.2) and MPAG (513.6>207.2). RESULTS: A total analysis
      time of 5 min was needed to separate MPA and MPAG. The method was linear between
      0.05 and 50 mg/L for MPA. Analytical recoveries were >95%. Variation coefficients
      ranged between 3.1 and 4.1%. Method comparison for MPA was performed using a
      commercial HPLC-UV test. The Pearson correlation coefficients were >0.9. The
      Bland-Altman plot showed an excellent agreement between LC-MS/MS and HPLC-UV
      quantification. CONCLUSION: We present a robust online SPE-LC-MS/MS platform for
      a simultaneous and fast daily therapeutic drug monitoring of five
      immunosuppressive drugs in whole blood and plasma samples.

PMID- 16806143
TI  - The evaluation of altered redox status in plasma and mitochondria of acute and
      chronic diabetic rats.
AB  - OBJECTIVES: An increase in plasma oxidative stress and decreased mitochondrial
      lipid hydroperoxides may contribute to the imbalance in the redox status between
      intramitochondrial and extramitochondrial milieu in chronic experimental diabetic
      rats. DESIGN AND METHODS: To determine the effect of hyperglycemia in promoting
      redox imbalance, we determined lipid hydroperoxides (LHP), protein carbonyl
      (PCO), total antioxidant activity (ferric reducing/antioxidant power; FRAP) and
      albumin as markers of redox status of plasma, and mitochondrial lipid
      hydroperoxide levels as a marker of lipid peroxidation in liver, pancreas and
      kidney tissue of acute and chronic diabetic male Sprague-Dawley rats and their
      controls. The levels of the studied markers were determined by colorimetric
      methods. RESULTS: Plasma and mitochondrial oxidative stress parameter levels of
      acute diabetic rats were not significantly different from their controls. Plasma
      LHP and PCO levels of chronic diabetic rats were increased significantly as
      compared to those of both acute diabetic rats and the controls. Plasma FRAP
      levels of chronic diabetic animals were decreased significantly as compared to
      those of the controls. On the other hand, LHP levels in liver, pancreas and
      kidney mitochondria of chronic diabetic rats were decreased significantly as
      compared to those of both acute diabetic rats and the controls. We observed a
      negative correlation between LHP levels in liver mitochondria of chronic diabetic
      rats, and PCO and fructosamine levels in plasma of chronic diabetic rats were
      correlated. LHP levels in the pancreatic mitochondria of chronic diabetic rats
      and plasma oxidative stress parameters of chronic diabetic rats were not
      significantly correlated. LHP levels in kidney mitochondria of chronic diabetic
      rats were significantly correlated with serum albumin. There was no correlation
      between LHP levels in kidney mitochondria and other plasma oxidative stress
      parameters in chronic diabetic rats. CONCLUSIONS: Our data suggest that redox
      imbalance between plasma and liver mitochondria might become a major threat to
      chronic diabetic rats.

PMID- 16806144
TI  - Utilization of recombinant Fab fragments in a cTnI immunoassay conducted in spot
      wells.
AB  - OBJECTIVES: To evaluate the performance of a new cTnI immunoassay utilizing site
      specifically biotinylated recombinant Fab fragments on recently established spot
      wells. DESIGN AND METHODS: Two different cTnI-specific recombinant site
      specifically biotinylated Fab fragments were produced. The performance of the new
      sandwich-type cTnI immunoassay in spot wells was evaluated in terms of binding
      capacity, assay kinetics and assay sensitivity and compared with a cTnI
      immunoassay carried out in conventional microtitration wells. Furthermore, the
      functionality of the recombinant Fab fragments was compared to the corresponding
      monoclonal antibodies in assay with one, two or three capture antibodies.
      RESULTS: The signal-to-background level was improved, providing an analytical
      detection limit of 0.002 microg/l with a surface of two capture Fab fragments.
      The spot wells increased the signal levels 2-fold and a further 4-fold
      improvement was detected with the Fab fragments already after 5 min assay time.
      CONCLUSIONS: The spot-concept in combination with site-oriented capture Fab
      fragments carries great promise as a very useful approach to improve the
      immunoassay performance of future point-of-care cTnI assays.

PMID- 16806145
TI  - Novel comparison of capillary electrophoresis versus immunoassay in the
      measurement of total percent carbohydrate deficient transferrin.
AB  - OBJECTIVES: Novel comparison of CDT isoforms as determined by CE with an FDA
      approved immunoassay kit. DESIGN AND METHODS: Subjects (n=51) were categorized by
      drinking status based on AUDIT questionnaire responses. CDT isoform analyses by
      CE were compared to a commercially available, FDA-approved immunoassay. The
      analytical specificity of the immunoassay kit was assessed by analysis with IEF.
      RESULTS: Because of the poor correlation between % CDT as measured by CE and the
      TIA immunoassay and between subject-reported drinking levels and results from the
      TIA assay, extraction column eluants from the immunoassays were analyzed by IEF
      for analytical specificity. % CDT by TIA included some trisialo-Tf, a non-CDT
      fraction, in the % CDT determination. CONCLUSIONS: Total % CDT by CE, which
      separates all isoforms is more analytically specific than immunoassays because it
      does not include trisialo-Tf in the CDT calculation.

PMID- 16806146
TI  - Slight association between type 1 diabetes and "ff" VDR FokI genotype in patients
      from the Italian Lazio Region. Lack of association with diabetes complications.
AB  - BACKGROUND: Vitamin D receptor (VDR) mediates the effects of vitamin D. Our paper
      evaluates the FokI and BsmI VDR genotypes in 246 Caucasian (Italian from Lazio
      Region) T1DM patients compared with 246 Caucasian healthy controls, sharing age
      and gender and regional provenience with the patients. In addition, T1DM patients
      without complications were compared with those carrying three complications.
      METHODS: Genotyping has been obtained by RFLP-PCR technique. RESULTS: A slight
      significant association of T1DM with FokI homozygous "f" genotype was observed.
      No association was observed with the presence of multiple complications by a
      multivariate analysis. CONCLUSION: T1DM patients showed slightly increased
      prevalence of "ff" VDR genotype.

PMID- 16806147
TI  - Developmental relocation of presynaptic terminals along distinct types of
      dendritic filopodia.
AB  - Dendritic filopodia are long thin protrusions occurring predominantly on
      developing neurons. Data from different systems suggest a range of crucial
      functions for filopodia in central circuit formation, including steering of
      dendritic growth, branch formation, synaptogenesis, and spinogenesis. Are the
      same filopodia competent to mediate all these processes, do filopodia acquire
      different functions through development, or do different filopodial types with
      distinct functions exist? In this study, 3-dimensional reconstructions from
      confocal image stacks demonstrate the existence of two morphologically and
      functionally distinct types of filopodia located on the dendritic tips versus the
      dendritic shafts of the same developing motoneuron. During dendritic growth, both
      filopodial types undergo a process of stage-specific morphogenesis. Using novel
      quantification strategies of 3-dimensional co-localization analysis for
      immunocytochemically labeled presynaptic specializations along postsynaptic
      filopodia, we find that presynaptic terminals accumulate along filopodia towards
      the dendrites at both stable dendritic shafts and on growing dendritic tips. On
      tips, this is likely to reflect synaptotrophic growth of the dendrite. At stable
      shafts, however, presynaptic sites become relocated along filopodia towards
      dendritic branches. This indicates the interactive growth of both pre- and
      postsynaptic partner towards one another during synaptogenesis, using filopodia
      as guides.

PMID- 16806148
TI  - Gonadotrope and thyrotrope development in the human and mouse anterior pituitary
      gland.
AB  - Genes and orthologous intrinsic and extrinsic factors critical for embryonic
      pituitary gonadotrope and thyrotrope cell differentiation have been identified
      mainly in rodents, but data on the human are very limited. In human fetal
      pituitaries examined between 14 and 19 weeks of gestation using immunofluorescent
      confocal microscopy, we found that most fetal gonadotropes expressed alpha-GSU,
      LHbeta, and FSHbeta gonadotropin subunits while almost no cells expressed alpha
      GSU and LHbeta alone. Gonadotropes expressing alpha-GSU and FSHbeta only were
      detected in both male and female pituitaries, increasing in proportion to total
      gonadotropes in both males and females from 14 (approximately 4.5%) to 19 weeks
      (approximately 16.5%) with a peak in males of 45.5% compared with females of
      16.5% at 17 weeks of gestation. When FSHbeta or LHbeta genes were expressed,
      gonadotropes were non-dividing. This profile of human fetal gonadotrope
      development differs from the current mouse model. Furthermore, while expression
      of alpha-GSU appears to be the lead protein in gonadotropes, in thyrotropes which
      ultimately express alpha-GSU with TSHbeta, we observed that most if not all
      thyrotropes were TSHbeta-positive but alpha-GSU-negative until around 19 weeks in
      human, and e15 in mouse, fetal pituitaries. Furthermore, the TSHbeta-only
      thyrotropes were dividing, and TSHbeta rather than alpha-GSU was the lead protein
      in thyrotrope development. Thus, while biologically active dimeric FSH and LH can
      be produced by the human fetal pituitary by 14 weeks, dimeric biologically active
      TSH will only be produced from around 17 weeks of gestation. The mechanism(s)
      responsible for the different molecular regulation of alpha-GSU gene expression
      in gonadotropes and thyrotropes in the developing human fetal pituitary now
      requires investigation.

PMID- 16806149
TI  - Retinoic acid regulates morphogenesis and patterning of posterior foregut
      derivatives.
AB  - Retinoic acid (RA) is an embryonic signaling molecule regulating a wide array of
      target genes, thereby being a master regulator of patterning and differentiation
      in a variety of organs. Here we show that mouse embryos deficient for the RA
      synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2), if rescued from early
      lethality by maternal RA supplementation between E7.5 and E8.5, lack active RA
      signaling in the foregut region. The resulting mutants completely fail to develop
      lungs. Development of more posterior foregut derivatives (stomach and duodenum),
      as well as liver growth, is also severely affected. A primary lung bud is
      specified in the RA-deficient embryos, which fails to outgrow due to defective
      FGF10 signaling and lack of activation of FGF-target genes, such as Pea3 and Bmp4
      in the epithelium. Specific Hox and Tbx genes may mediate these RA regulatory
      effects. Development of foregut derivatives can be partly restored in mutants by
      extending the RA supplementation until at least E10.5, but lung growth and
      branching remain defective and a hypoplastic lung develops on the right side
      only. Such conditions poorly restore FGF10 signaling in the lung buds. Explant
      culture of RALDH2-deficient foreguts show a capacity to undergo lung budding and
      early branching in the presence of RA or FGF10. Our data implicate RA as a
      regulator of gene expression in the early embryonic lung and stomach region
      upstream of Hox, Tbx and FGF10 signaling.

PMID- 16806150
TI  - Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin
      41 in C. elegans male tail tip morphogenesis.
AB  - To gain an understanding of the genes and mechanisms that govern morphogenesis
      and its evolution, we have analyzed mutations that disrupt this process in a
      simple model structure, the male tail tip of the rhabditid nematode C. elegans.
      During the evolution of rhabditid male tails, there have been several independent
      changes from tails with rounded tips ("peloderan", as in C. elegans) to those
      with pointed tips ("leptoderan"). Mutations which produce leptoderan (Lep) tails
      in C. elegans thus identify candidate genes and pathways in which evolutionary
      changes could have produced leptoderan tails from peloderan ancestors. Here we
      report that two novel, gain-of-function (gf) alleles of lin-41 have lesions
      predicted to affect the N-terminus of the RBCC-domain LIN-41 protein. Both gf
      alleles cause the tail tip of adult males to retain the pointed shape of the
      juvenile tails, producing a Lep phenotype that looks like the tails of leptoderan
      species. Consistent with its role in the heterochronic pathway, we find that lin
      41 governs the timing and extent of male tail tip morphogenesis in a dose
      dependent manner. Specifically, the Lep phenotype results from a heterochronic
      delay in the retraction and fusion of the tail tip cells during L4 morphogenesis,
      such that retraction is not completed before the adult molt. Conversely, we find
      that tail tip morphogenesis and cell fusions begin precociously at the L3 stage
      in the reduced-function lin-41 mutant, ma104, resulting in over-retracted male
      tails in the adult. Because modulated anti-LIN-41 RNAi knockdowns in the gf
      mutants restore wild-type phenotype, we suggest that the leptoderan phenotype of
      the gf alleles is due to a higher activity of otherwise normal LIN-41.
      Additionally, the gf allele is suppressed by the wild-type allele, suggesting
      that LIN-41 normally regulates itself, possibly by autoubiquitination. We
      speculate that small changes affecting LIN-41 could have been significant for
      male tail evolution.

PMID- 16806151
TI  - Temporal identity transition in the avian cerebellar rhombic lip.
AB  - The rhombic lip is a discrete strip of neuroepithelium bordering the roofplate of
      the fourth ventricle, which gives rise to a defined sequence of migratory
      neuronal derivatives. In rhombomere 1 of the chick, early born cells give rise to
      post-mitotic hindbrain nuclei, while later derivatives comprise of cerebellar
      granule cell precursors, a unique proliferative, migratory precursor population
      that forms the external granule cell layer. We have examined the temporal
      specification of these two populations using a heterochronic grafting strategy,
      in ovo. When transplanted into younger neural tube, rhombic lip cells maintain
      their characteristic molecular markers and migrate into the hindbrain. Granule
      cell precursor derivatives of late grafts are, in addition, able to exploit
      neural crest streams to populate the branchial arches. Within the neural tube,
      derivatives of early and late rhombic lip progenitors display patterns of
      migration and process extension, characterised by specific trajectories and
      targets, which are consistent with their temporal origin. However, the normal
      temporal progression of cell production is disrupted in grafted progenitors:
      transplanted early rhombic lip fails to subsequently produce granule cell
      precursors. This indicates that, while the behaviour of derivatives is
      intrinsically specified at the rhombic lip, the orderly temporal transition in
      cell type production is dependent on extrinsic cues present only in the later
      embryo.

PMID- 16806152
TI  - The Xdsg protein in presumptive primordial germ cells (pPGCs) is essential to
      their differentiation into PGCs in Xenopus.
AB  - In order to know the role of the Xdsg gene in presumptive PGCs (pPGCs) of
      Xenopus, we attempted to inhibit the translation of Xdsg mRNA in pPGCs by
      injecting antisense morpholino oligo (asMO), together with Fluorescein Dextran
      Lysine (FDL), into single germ plasm-bearing cells of 32-cell embryos. Among
      three types of asMOs complementary to different parts of the 5'-untranslated
      region of Xdsg mRNA tested, only one asMO, designated as Xdsg-3, inhibited the
      translation of the mRNA in FDL-labeled pPGCs, resulting in the absence of labeled
      PGCs in experimental tadpoles. On the other hand, two other asMOs, Xdsg-1 and -2,
      did not inhibit the translation, so that a similar number of labeled PGCs found
      in FDL-injected but asMO-uninjected control tadpoles were observed in
      experimental tadpoles derived from asMO-injected embryos. Surprisingly, use of
      Xdsg-3 asMO resulted in the disappearance of the protein of Xenopus vasa homolog
      (Xenopus vasa-like gene 1, XVLG1) from FDL-labeled pPGCs by inhibiting the
      translation of XVLG1 mRNA. However, the effect of Xdsg-3 asMO on the translation
      of Xdsg and XVLG1 mRNAs and PGC formation could be canceled by the coinjection
      with Xdsg mRNA. Consequently, the Xdsg protein in pPGCs may play an important
      role in the formation of PGCs by regulating the production of XVLG1 protein.

PMID- 16806153
TI  - Misexpression of acetylcholinesterases in the C. elegans pha-2 mutant accompanies
      ultrastructural defects in pharyngeal muscle cells.
AB  - pha-2 is the Caenorhabditis elegans homolog of the vertebrate homeobox gene Hex.
      Embryonic expression of pha-2 is mostly pharyngeal and the only described mutant
      allele of pha-2 results in a severe pharyngeal defect in which certain muscle
      cells (pm5 cells) and neurons are grossly deformed. Here, we performed a detailed
      characterization of the pha-2 phenotype using cell-type-specific reporters,
      physical manipulation of the nuclei in pharyngeal muscle cells using "optical
      tweezers", electron microscopy, staining of the actin cytoskeleton as well as
      phenotypic rescue and ectopic expression experiments. The main findings of the
      present study are (i) the pha-2 (ad472) mutation specifically impairs the
      pharyngeal expression of pha-2; (ii) in the pha-2 mutant, the cytoskeleton of the
      pm5 cells is measurably weaker than in normal cells and is severely disrupted by
      large tubular structures and organelles; (iii) the pm5 cells of the pha-2 mutant
      fail to express the acetylcholinesterase genes ace-1 and ace-2; (iv) ectopic
      expression of pha-2 can induce ectopic expression of ace-1 and ace-2; and (v) the
      anc-1 mutant with mislocalized pm5 cell nuclei occasionally shows an isthmus
      phenotype similar to that of pha-2 worms.

PMID- 16806154
TI  - A group 13 homeodomain is neither necessary nor sufficient for posterior
      prevalence in the mouse limb.
AB  - Posterior prevalence is the general property attributed to HOX proteins
      describing the dominant effect of more posterior HOX proteins over the function
      of anterior orthologs in common areas of expression. To explore the HOX group 13
      protein domains required for this property, we used the mouse Prx-1 promoter to
      drive transgenic expression of Hox constructs throughout the entire limb bud
      during development. This system allowed us to conclusively demonstrate a
      hierarchy of Hox function in developing limbs. Furthermore, by substituting the
      HOXD11 or HOXA9 homeodomain for that of HOXD13, we show that a HOXD13 homeodomain
      is not necessary for posterior prevalence. Proximal expression of these chimeric
      proteins unexpectedly caused defects consistent with wild-type HOXD13 mediated
      posterior prevalence. Moreover, group 13 non-homeodomain residues appear to
      confer the property as proximal expression of HOXA9 containing the HOXD13
      homeodomain did not result in limb reductions characteristic of HOXD13. These
      data are most compatible with models of posterior prevalence based on protein
      protein interactions and support examination of the N-terminal non-homeodomain
      regions of Hox group 13 proteins as necessary agents for posterior prevalence.

PMID- 16806155
TI  - Dickkopf related genes are components of the positional value gradient in Hydra.
AB  - Hydra is a classical model organism to understand fundamental developmental
      biological processes such as regeneration and axis formation. Here, we show that
      two genes which share some similarity with members of the Dickkopf family of
      proteins, HyDkk1/2/4-A and HyDkk1/2/4-C, are co-expressed in gland cells and
      regulated by the positional value gradient. While HyDkk1/2/4-A is expressed
      throughout the gastric region, HyDkk1/2/4-C has a graded expression pattern with
      a high level of transcripts just below the tentacle zone and absence of
      expression in the budding zone. Blocking the activity of GSK-3beta caused a
      drastic downregulation of HyDkk1/2/4-C expression in the gastric tissue.
      Experimental reduction of the number of HyDkk1/2/4-C-expressing cells resulted in
      expansion of the HyWnt expression domain in the hypostome. Thus, similar to
      Dickkopf proteins in vertebrates, one of the functions of HyDkk1/2/4-C in hydra
      may be to antagonize Wnt signalling.

PMID- 16806156
TI  - Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during
      facial morphogenesis and palatal fusion.
AB  - Transforming growth factor beta (TGF-beta) proteins play important roles in
      morphogenesis of many craniofacial tissues; however, detailed biological
      mechanisms of TGF-beta action, particularly in vivo, are still poorly understood.
      Here, we deleted the TGF-beta type I receptor gene Alk5 specifically in the
      embryonic ectodermal and neural crest cell lineages. Failure in signaling via
      this receptor, either in the epithelium or in the mesenchyme, caused severe
      craniofacial defects including cleft palate. Moreover, the facial phenotypes of
      neural crest-specific Alk5 mutants included devastating facial cleft and appeared
      significantly more severe than the defects seen in corresponding mutants lacking
      the TGF-beta type II receptor (TGFbetaRII), a prototypical binding partner of
      ALK5. Our data indicate that ALK5 plays unique, non-redundant cell-autonomous
      roles during facial development. Remarkable divergence between Tgfbr2 and Alk5
      phenotypes, together with our biochemical in vitro data, imply that (1) ALK5
      mediates signaling of a diverse set of ligands not limited to the three isoforms
      of TGF-beta, and (2) ALK5 acts also in conjunction with type II receptors other
      than TGFbetaRII.

PMID- 16806157
TI  - Implication of site quality on mitochondrial electron transport activity and its
      interaction with temperature in feral Mya arenaria clams from the Saguenay Fjord.
AB  - The advent of global warming has given rise to questions about the impact of
      temperature/pollution interactions on the integrity of certain benthic organisms
      like bivalves. This interaction was examined in intertidal Mya arenaria clams
      from the Saguenay Fjord using the concepts of cellular energy allocation and
      temperature-dependent mitochondrial electron transport (METT) activity. Clams
      were collected at low tide from six sites (two clean, four polluted) for
      determinations of condition factor (weight/shell length), growth index (age-to
      length ratio), gonadal lipids and maturation index, gonad MET at various habitat
      temperatures, METT, gill xanthine oxidase and gill DNA damage. Condition factor
      was generally lower at the four polluted sites, with growth index being severely
      affected at two of them. Gonadal maturation was also significantly dampened at
      two of the four pollution-impacted sites. Gill xanthine oxidase (purine bases
      salvage pathway) and DNA strand breaks were significantly increased at most of
      the polluted sites, confirming pollution-mediated damage in clams. Moreover, MET
      at 20 degrees C, METT and gonad lipids were significantly induced at the polluted
      sites. Clam condition factor was negatively correlated with most of the
      biomarkers for cellular energy allocation (gonadal lipids, MET and METT), but not
      with gonadal maturation. DNA damage and xanthine oxidase were positively
      correlated with MET at 20 degrees C and METT. This is the first report of
      electron transport in mitochondria being more sensitive to incremental
      temperature increases in clams under pollution stress. The gradual warming of
      clam habitats would likely worsen the impacts of pollution in feral clam
      populations.

PMID- 16806158
TI  - Protections of pinocembrin on brain mitochondria contribute to cognitive
      improvement in chronic cerebral hypoperfused rats.
AB  - To study effects of pinocembrin, a natural compound extracted from propolis, on
      cognitive ability impaired by chronic cerebral hypoperfusion in rats, and if it
      did so, to investigate its effects on brain mitochondria. Rat chronic cerebral
      hypoperfusion was achieved by permanent bilateral common carotid arteries
      ligation, with regional cerebral blood flow evaluated. Cognitive ability was
      tested by Morris water maze task. Production of reactive oxygen species and
      origin targets including mitochondria membrane potential, respiratory chain
      complex I, complex III activities and mitochondria swelling degree were
      evaluated. Cytochrome oxidase was determined on its expression level by western
      blotting. Pinocembrin alleviated cognitive impairments in Morris water maze and
      decreased mitochondria reactive oxygen species production, in accordance with its
      improvements on complex I activity, membrane potential level, mitochondria
      swelling degree and cytochrome oxidase deficits. Pinocembrin could improve rat
      cognitive impairments induced by chronic cerebral hypoperfusion, contributed to
      its protections on brain mitochondria structure and function.

PMID- 16806159
TI  - Induction of Fas clustering and apoptosis by coral prostanoid in human hormone
      resistant prostate cancer cells.
AB  - Cyclopentenone prostaglandins (PGs) such as PGA1, PGA2 and delta12-PGJ2 have been
      shown to suppress tumor cell growth and to induce apoptosis in prostate cancer
      cells. Bromovulone III, which is isolated from the soft coral Clavularia viridis,
      is a cyclopentenone prostanoid. In this study, the anti-tumor activity as well as
      action mechanism of bromovulone III was identified in prostate cancer cells.
      Bromovulone III displayed anti-tumor activity of 30 to 100 times more effective
      than PGA1, PGA2 and delta12-PGJ2 in PC-3 cells. Several targets of caspases and
      Bcl-2 family of proteins were detected and the data demonstrated that bromovulone
      III induced the activation of caspase-8, -9 and -3, and Bid cleavage in which the
      caspase-8 activation occurred the first. Bromovulone III did not modify the
      protein levels of death receptors and ligands. Of note, the Fas clustering in PC
      3 cells responsive to bromovulone III was observed by confocal immunofluorescence
      microscopy suggesting the involvement of Fas-mediated pathway. Bromovulone III
      also induced the cleavage of Mcl-1 in this study. The cleavage fragments (24, 19
      and 17 kDa) may partly share the apoptotic insult. Although it has been suggested
      that Fas-mediated signaling may contribute to the caspase-8 activation induced by
      DNA-damaging agents; however, bromovulone III did not induce any DNA breakage,
      suggesting that bromovulone III-induced Fas/caspase-8-dependent signaling is not
      through the direct target on DNA damage. In summary, the data suggest that
      bromovulone III causes a rapid redistribution and clustering of Fas in PC-3
      cells. Subsequently, the Fas event causes the activation and interaction of
      caspase-8/Bid/caspase-9 signaling cascades, and the activation of executor
      caspase-3.

PMID- 16806160
TI  - Sildenafil reduces cardiovascular remodeling associated with hypertensive
      cardiomyopathy in NOS inhibitor-treated rats.
AB  - Many of the physiological responses to nitric oxide (NO) are mediated by cyclic
      5'-guanosine monophosphate (cGMP), the intracellular levels of which are
      regulated by phosphodiesterase type 5 (PDE5). In situations of reduced NO
      formation, the inhibition of PDE5 by selective inhibitors such as sildenafil
      could be beneficial in restoring physiological functions by enhancing the
      intracellular levels of cGMP. In this study, we evaluated the effects of
      sildenafil on the hemodynamic and histological alterations induced by the chronic
      treatment of rats with N(omega)-nitro-L-arginine-methyl ester (L-NAME). After 8
      weeks of concomitant treatment with sildenafil and L-NAME, arterial blood
      pressure was significantly lower (P<0.05) than in L-NAME-treated rats. The fall
      in blood pressure was associated with a slight reduction in the total peripheral
      vascular resistance (P<0.05). Sildenafil partially prevented the decrease in
      cardiac output seen in L-NAME-treated rats. Morphologically, sildenafil reduced
      the total area of the myocardial lesions and attenuated the cardiomyocyte and
      vascular smooth muscle remodeling seen with L-NAME. These results show that
      sildenafil prevented the deleterious hemodynamic and morphological alterations
      associated with L-NAME-induced hypertension. This beneficial effect was probably
      mediated by an increase in cardiac and vascular cGMP levels as reflected in
      circulating plasma cGMP levels.

PMID- 16806161
TI  - Cyclic phosphatidic acid stimulates respiration without producing vasopressor or
      tachycardiac effects in rats.
AB  - The effects of a novel lipid mediator, cyclic phosphatidic acid (cPA), on
      respiratory and cardiovascular functions were examined in anesthetized rats.
      Intravenous (i.v.) administration of 3-O-carba-oleoyl-cPA at doses of 130 and 390
      microg/kg produced dose-dependent increases in tidal volume and respiratory
      frequency, resulting in an increase in total ventilation. Heart rate was slightly
      decreased at a dose of 390 microg/kg, while systemic arterial pressure was not
      affected. Bilateral section of vagi and carotid sinus nerves designed to
      eliminate major regulatory inputs from the peripheral afferents to the
      respiratory center reduced these responses, but did not abolish them. These
      results indicate that cPA stimulates respiration, via central and peripheral
      mechanisms acting on the central respiratory rhythm generator in the brain stem.
      Administration of cPA may be of therapeutic value as a respiratory stimulant
      without producing vasopressor or tachycardiac effects, for treatment of
      respiratory disorders.

PMID- 16806162
TI  - Isoflurane preconditioning protects human neuroblastoma SH-SY5Y cells against in
      vitro simulated ischemia-reperfusion through the activation of extracellular
      signal-regulated kinases pathway.
AB  - It has been reported that a prior exposure of isoflurane, a commonly used
      volatile anesthetic in clinical practice, reduces brain cell death after
      ischemia. This isoflurane preconditioning-induced neuroprotection has been shown
      in rat in vivo and in vitro brain ischemia models. To investigate the mechanisms
      of this protection, we used the human neuroblastoma SH-SY5Y cells and simulated
      ischemia in vitro by oxygen-glucose deprivation. We found that isoflurane
      exposure for 30 min at 24 h before a 5-h oxygen-glucose deprivation dose
      dependently reduced cell death. Isoflurane exposure induced
      phosphorylation/activation of extracellular signal-regulated kinase (ERK).
      Inhibition of the phospho-ERK expression abolished the isoflurane preconditioning
      induced protection. Isoflurane exposure also increased the expression of early
      growth response gene 1 (Egr-1) and Bcl-2, proteins downstream of ERK. Egr-1 is a
      transcription factor and plays a role in cell survival. Bcl-2 is an anti
      apoptotic protein. The increased expression of Egr-1 and Bcl-2 by isoflurane was
      inhibited by ERK inhibition. Thus, our results suggest a role of ERK/Egr-1/Bcl-2
      pathway in the isoflurane preconditioning-induced protection in the human
      neuroblastoma SH-SY5Y cells.

PMID- 16806163
TI  - Early tolerance to the hypophagic effect of the cannabinoid receptor antagonist
      SR141716 does not impede blockade of an orexigenic stimulus.
AB  - The cannabinoid CB1 receptor antagonist SR141716 (Rimonabant) is known to reduce
      food intake by central and peripheral mechanisms. Recently, SR141716 has been
      reported to block the orexigenic effect of ghrelin, a potent orexigenic peptide
      produced by the stomach. This study investigated whether in rats, made tolerant
      to the hypophagic effect of SR141716, the drug was still capable to block the
      orexigenic activity of another non-natural (hypothalamic) peptide, i.e., the
      growth hormone releasing peptide (GHRP) hexarelin, a ghrelin mimetic. In the
      acute experiments, each dose of SR141716 (1, 5 and 10 mg/kg i.p.) reduced food
      intake with respect to vehicle-treated rats, whereas hexarelin (160 microg/kg
      s.c.) markedly stimulated feeding. All doses of SR141716 were capable to reduce
      the orexigenic effect of the GHRP. A 15-day administration of SR141716 (10 mg/kg
      i.p.) reduced both food intake and body weight. Tolerance to the hypophagic
      effect of SR141716 developed within 5 days, but in contrast, body weight remained
      markedly below that of vehicle-treated group throughout the entire treatment
      period. Interestingly, despite development of tolerance to its hypophagic effect,
      SR141716 was capable to suppress the orexigenic effect of repeated hexarelin
      challenge tests performed throughout the chronic experiments. In conclusion, the
      results of the present study confirm and broaden the existence of a functional
      relationship between ghrelin and endocannabinoids in the control of food intake,
      and bespeak the ability of a CB1 receptor antagonist to suppress orexia caused by
      stimuli alien to direct stimulation of the cannabinoid system.

PMID- 16806164
TI  - Ligustilide inhibits vascular smooth muscle cells proliferation.
AB  - Proliferation and migration of vascular smooth muscle cells (VSMCs) are believed
      to develop atherosclerosis and venous bypass graft disease. Ligustilide is widely
      used to treat some pathological settings such as atherosclerosis and
      hypertension. The aim of this study was to examine the effect of ligustilide on
      VSMCs proliferation. The results show that ligustilide significantly inhibited
      VSMCs proliferation and cell cycle progression. Further analysis shows that
      ligustilide suppressed reactive oxygen species production and extracellular
      signal-related kinases (ERK), c-Jun N-terminal protein kinase (JNK), and p38 MAP
      kinase. Cells were treated with antioxidant, superoxide dismutase, catalase, and
      DPI, respectively, leading to repress ERK, JNK, and p38 activation. The
      inhibitors of mitogen activated protein kinase (MAPK), PD98059, SB203580, and
      Sp600125, inhibited cell proliferation. These findings suggest the
      antiproliferative effect of ligustilide was associated with the decrement of
      reactive oxygen species resulting in the suppression of MAPK pathway. Thus,
      ligustilide contribute to be the effective agent in preventing cardiovascular
      diseases.

PMID- 16806165
TI  - Serofendic acid, a neuroprotective substance derived from fetal calf serum,
      inhibits mitochondrial membrane depolarization and caspase-3 activation.
AB  - We have previously reported that a neuroprotective substance, serofendic acid,
      was purified and isolated from fetal calf serum. Here, we investigated the effect
      of serofendic acid on glutamate-induced apoptosis using rat primary cultures of
      cortical neurons. Exposure of the cortical cultures to relatively low
      concentration of glutamate (100 microM) induced neuronal death and nuclear
      fragmentation. Glutamate exposure also induced a transient increase in caspase-3
      activity. A membrane-permeable inhibitor of caspase-3 (DEVD-CHO) prevented the
      glutamate neurotoxicity. Serofendic acid (0.01-10 microM) markedly prevented
      glutamate-induced apoptotic neuronal death and nuclear fragmentation. To
      elucidate the protective mechanism of serofendic acid, we first examined the
      effect on the glutamate-induced increase in intracellular Ca2+ concentration.
      Glutamate-induced increase in intracellular Ca2+ concentration was significantly
      inhibited by MK-801, a NMDA receptor antagonist, but not by serofendic acid.
      Next, we investigated the effect of serofendic acid on the loss of mitochondrial
      membrane potential induced by glutamate by using a fluorescence indicator,
      tetramethylrhodamine methyl ester (TMRM). Glutamate exposure resulted in a rapid
      reduction of TMRM fluorescence, indicating that mitochondrial membrane was
      depolarized by glutamate. Serofendic acid prevented the loss of mitochondrial
      membrane potential following glutamate exposure. Moreover, serofendic acid
      reduced the activation of caspase-3 induced by glutamate. Finally, serofendic
      acid directly inhibited the activity of recombinant human caspase-3, -7 and -8 at
      higher concentrations. These results indicate that serofendic acid prevents
      glutamate-induced apoptosis in cultured cortical neurons by the prevention of
      loss of mitochondrial membrane potential and the reduction of the process of
      caspase-3 activation.

PMID- 16806166
TI  - Pro-invasive gene regulating effect of irradiation and combined temozolomide
      radiation treatment on surviving human malignant glioma cells.
AB  - The current chemotherapeutic treatment of glioblastoma patients has minor
      success. Little is known about the molecular and cellular mechanisms of the
      resistance of gliomas towards current therapies. This study investigated both
      suppressive cellular effects and regulation of extracellular matrix remodeling
      proteins with pro-invasive activity in surviving human glioblastoma cells under
      clinically relevant treatments. All cellular and molecular biological
      investigations were performed on the genetically well-defined and clinically
      relevant p53-wild type U87Mg glioma cells. Malignant glioma cells underwent
      either radiation or temozolomide treatments alone, or combined chemo/radio
      treatment. Protein expression patterns were investigated by two-dimensional
      polyacrylamide gel electrophoresis followed by protein spot identification using
      tandem mass spectrometry analysis. Specific expression levels were quantified by
      Western-blotting. Extracellular gelatinase activities for both metalloproteinases
      MMP-2 and MMP-9 were determined by zymogramms. Survival curves indicated no
      effective suppression of glioma cells under all treatment conditions tested.
      Morphological changes demonstrated sub-lethal effect of both temozolomide and
      combined treatment. Expression of MMP-2, MMP-9, and membrane type 1 matrix
      metalloproteinases (MT1-MMP) was differentially up-regulated by increasing
      cellular density and treatment conditions. A significantly enhanced extracellular
      degrading activity under all treatment conditions tested was demonstrated for MMP
      2 only. Being a marker for brain tumour progression and angiogenesis, lysozyme c
      was highly up-regulated under the combined chemo/radio treatment. The activation
      of proteins with pro-invasive activity indicates an increasing malignancy grade
      of surviving glioma cells under treatment conditions tested correlating well with
      more aggressive tumour phenotypes observed clinically in recurrences of treated
      glioblastomas.

PMID- 16806167
TI  - Sertindole, in contrast to clozapine and olanzapine, does not disrupt water maze
      performance after acute or chronic treatment.
AB  - Cognitive deficits in schizophrenia are associated with poor functional outcome,
      and may be further aggravated by treatment with antipsychotics. In the present
      study the acute and chronic (3 weeks of treatment) effects of clozapine,
      olanzapine, and sertindole on performance in the Morris water maze in rats was
      compared, using pharmacologically and/or clinically relevant dose regimens. An
      experimental design consisting of three trials/day over 3 days was used.
      Performance was expressed as the distance and latency to find a submerged
      platform, as well as the percentage of "non-finders", i.e. percentage of trials
      where the rat was unable to find the platform within the total trial time of 60
      s. Clozapine (40 mg/kg, p.o.) and olanzapine (2.5 mg/kg, s.c.) impaired water
      maze performance when given acutely. However, tolerance developed to the deficit
      induced by clozapine, whereas the olanzapine-mediated impairment was enhanced
      after chronic treatment. Sertindole (2.5 mg/kg, p.o.) had no disruptive effect on
      performance after either acute or chronic treatment. Exposure measurements
      confirmed that all three compounds were present in the serum at least at
      clinically effective concentrations. Thus, the three antipsychotics tested
      differentially affected rodent cognition, whereby sertindole appeared to have a
      lower potential than either clozapine or olanzapine to induce cognitive
      impairment. The hypothesis that the low potency of sertindole in inducing
      dopamine D2 receptor blockade, combined with lack of antimuscarinic and histamine
      H1 antagonist activity in vivo is discussed. Clearly further studies are needed
      to assess the potential cognition-enhancing effects of sertindole vs. other
      antipsychotics in a relevant animal model of schizophrenia.

PMID- 16806168
TI  - Effect of the anti-receptor ligand-blocking 225 monoclonal antibody on EGF
      receptor endocytosis and sorting.
AB  - The anti-receptor antibody, 225 mAb, is known to block binding of ligand to the
      epidermal growth factor receptor (EGFR). However, the effect of this neutralizing
      antibody on EGFR endocytosis, trafficking and degradation remains unclear. Here,
      we demonstrate that endocytosis of (125)I-225 mAb occurs, albeit with a slower
      rate than that of EGF. Using pulse chase assays, we show that internalized (125)I
      225 mAb is recycled to the surface much more efficiently than internalized (125)I
      EGF. Also, we found that internalization of (125)I-225 mAb, in contrast to that
      of EGF, is independent of receptor tyrosine kinase activity, as evidenced by its
      insensitivity to AG1478, a specific EGFR tyrosine kinase inhibitor. Analysis of
      the levels of cell surface and total EGFR showed that treatment with 225 mAb
      results in a 30-40% decrease in surface EGFR and a relatively slow downregulation
      of total EGFR. Taken together, these data indicate that 225 mAb induces
      internalization and downregulation of EGFR via a mechanism distinct from that
      underlying EGF-induced EGFR internalization and downregulation.

PMID- 16806169
TI  - Genetic visualization of neurogenesis.
AB  - Neurons are generated from stem or progenitor cells in discrete areas in the
      adult brain. The exact temporal and spatial distribution of adult neurogenesis
      has, however, been difficult to establish because of inherent limitations with
      the currently used techniques, and there are numerous controversies with regard
      to whether neurons are generated in specific regions or in response to insults.
      We describe here the generation of transgenic mice that express conditionally
      active Cre recombinase under the control of a nestin enhancer element. These mice
      allow the recombination of reporter alleles specifically in neural stem and
      progenitor cells and the visualization of their progeny in the adult brain. This
      offers a simple and efficient way to visualize live adult born neurons without
      the caveats of currently used techniques.

PMID- 16806170
TI  - HaCaT keratinocyte migration is dependent on epidermal growth factor receptor
      signaling and glycogen synthase kinase-3alpha.
AB  - After epithelial disruption by tissue injury, keratinocytes migrate from the
      wound edge into a provisional matrix. This process is stimulated by growth
      factors that signal through epidermal growth factor (EGF) receptor, including
      EGF, heparin-binding EGF-like growth factor (HB-EGF) and transforming growth
      factor-alpha (TGF-alpha), and by for example keratinocyte growth factor (KGF) and
      TGF-beta1 that function through different receptors. We have previously shown
      that keratinocyte migration induced by EGF or staurosporine is dependent on the
      activity of glycogen synthase kinase-3 (GSK-3). In the present study, we show
      that keratinocyte migration induced by TGF-beta1, KGF, EGF, TGF-alpha and
      staurosporine depends on EGFR signaling, involves autocrine HB-EGF expression and
      is potently blocked by GSK-3 inhibitors SB-415286 and LiCl. Inhibition of GSK-3
      also retards wound reepithelialization in vivo in mice. Moreover, inhibition of
      GSK-3 activity prevented cell rounding that is an early event in EGFR-mediated
      keratinocyte migration. Isoform-specific GSK-3alpha and GSK-3beta knockdown and
      overexpression experiments with siRNAs and adenoviral constructs, respectively,
      revealed that GSK-3alpha is required for keratinocyte migration, whereas
      excessive activity of GSK-3beta is inhibitory. Thus, induction of keratinocyte
      migration is conveyed through EGFR, promoted by endogenous HB-EGF and requires
      GSK-3alpha activity.

PMID- 16806171
TI  - Lens epithelial cells synthesize and secrete ceruloplasmin: effects of
      ceruloplasmin and transferrin on iron efflux and intracellular iron dynamics.
AB  - Although an essential nutrient, iron can catalyze damaging free radical
      reactions. Therefore elaborate mechanisms have evolved to carefully regulate iron
      metabolism. Ceruloplasmin, a protein with ferroxidase activity, and transferrin,
      an iron binding protein have important roles in maintaining iron homeostasis in
      cells. Since oxidative damage is a hallmark of cataractogenesis, it is essential
      to determine iron's role in lenticular physiology and pathology. In the current
      study of lens epithelial cells, the effects of ceruloplasmin and transferrin on
      intracellular distribution and efflux of iron were determined. Both ceruloplasmin
      and transferrin increased iron efflux from these cells and their effects were
      additive. Ceruloplasmin had significant effects on extracellular iron
      distribution only in cases of iron overload. Surprisingly, both transferrin and
      ceruloplasmin had significant effects on intracellular iron distribution. Under
      physiological conditions, ceruloplasmin increased iron incorporation into the
      storage protein, ferritin. Under conditions of iron overload, it decreased iron
      incorporation into ferritin, which is consistent with increased efflux of iron.
      Measurements of an intracellular chelatable iron pool indicated that both
      transferrin and ceruloplasmin increased the size of this pool at 24 h, but these
      increases had different downstream effects. Finally, lens epithelial cells made
      and secreted transferrin and ceruloplasmin. These results indicate an important
      role for these proteins in iron metabolism in the lens.

PMID- 16806172
TI  - Cellular redox state predicts in vitro corneal endothelial cell proliferation
      capacity.
AB  - Cellular redox state using the non-invasive mitochondrial autofluorescence
      technique of redox fluorometry was evaluated as a predictor for corneal
      endothelial proliferative capacity in vitro. Human corneal endothelial cells
      (HCEC) harvested from eye bank corneas were cultured in plates with two different
      coating substrates; type I collagen and poly-D-lysine. Cellular autofluorescence
      was measured with both DAPI (excitation: G365, emission: bandpass 445/50) and
      FITC (excitation: bandpass 450-490, emission bandpass 515-565) filter sets on
      days 3, 5, 7, and 14. The redox fluorometric ratio was calculated as net "DAPI"
      signal intensity divided by net "FITC" signal intensity. Normalized redox ratio
      was calculated as redox ratio divided by individual cell size. Cellular
      proliferation was analyzed by live cell count on days 2, 7, and 14. Mitochondrial
      staining was performed on days 4 and 14. The poly-d-lysine substrate decreased
      the proliferation capacity of HCEC in comparison to type I collagen out to 2
      weeks (p=0.045). The cellular redox fluorometric ratio decreased significantly as
      the cells proliferated (p<0.001). The cells cultured on type I collagen coated
      plates exhibited significantly lower redox fluorometric ratios than cells
      cultured on poly-D-lysine coated plates at day 7 (p=0.015). Normalized redox
      ratio showed significantly lower value in type I collagen coated plates at days 7
      (p=0.015) and 14 (p=0.039). Correlated cell proliferation capacity was
      significantly higher on type I collagen coating at days 7 and 14 (p=0.045 and
      p=0.049 respectively). HCECs showed different growth potential in vitro on
      different culture surface coating agents. This difference was well correlated
      with cellular redox ratios determined using redox fluorometry. Cellular redox
      ratio can be a potential predictor of cellular proliferation capacity.

PMID- 16806173
TI  - Does increased excitatory drive from the subthalamic nucleus contribute to
      dopaminergic neuronal death in Parkinson's disease?
AB  - Excitotoxicity has been suggested to play a pivotal role in the pathogenesis of
      Parkinson disease (PD). As subthalamic nucleus (STN) neurons express glutamate
      and are overactivated in parkinsonism, it seems that in PD dopaminergic (DA)
      neurons are under the influence of abnormally high levels of glutamate and
      consequently might be more vulnerable to neurodegeneration. To determine the
      contribution of the overactivated STN-SN pathway to the progression of PD, we
      studied the effect of prior unilateral STN lesion on the toxicity induced by
      subsequent administration of 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP)
      to non-human primates. In animals from group 1, kainic-induced lesion of the STN
      was performed prior to the administration of MPTP whereas in animals from group
      2, STN lesion was caused after animals had been chronically treated with MPTP.
      The lesion of the STN elicited a contralateral hemiballism in animals from group
      1, and they developed an asymmetrical parkinsonism after being exposed to MPTP.
      The STN lesion produced an improvement in the contralateral parkinsonism and mild
      choreic movements in animals from group 2. Cell counting of tyrosine hydroxylase
      immunoreactive (TH-ir) cells was performed by stereology and showed a similar
      loss of TH-ir cells (approximately 85%) in the ipsilateral and contralateral SN
      to the lesioned STN. These data indicate that the surgical removal of the
      excitatory drive from the STN to SN neurons does not protect dopaminergic neurons
      against a chronic and extended toxic effect of MPTP and do not support the
      assumption that STN blockade might delay the progression of PD.

PMID- 16806174
TI  - Nonhuman sialic acid Neu5Gc is very low in human embryonic stem cell-derived
      neural precursors differentiated with B27/N2 and noggin: implications for
      transplantation.
AB  - A concern recently has been raised that human embryonic stem cell (HESC) lines
      cultured with currently available methods may have limited clinical usefulness
      due to the immunogenicity of the nonhuman sialic acid Neu5Gc incorporated into
      their membranes during culturing. We find this concern has little relevance to
      neural differentiation protocols with B27/N2/noggin because of the gradual
      decline of Neu5Gc to less than 1% in differentiating cells upon switching to
      B27/N2 medium.

PMID- 16806175
TI  - Retrovirally delivered Islet-1 increases recruitment of Ng2 expressing cells from
      the postnatal SVZ into the striatum.
AB  - Neural stem and progenitor cells hold the promise to be used in cell-based
      therapies to treat both acute and degenerative neurological diseases. To date,
      most research has been focused on the use of in vitro propagated stem cells used
      as a source of cells in cell replacement therapies. However, mobilization of
      endogenous neural stem cells to generate a specific differentiated cell type
      offers an attractive alternative. In this study, we investigate the possibility
      to direct the formation of specific cells from the endogenous stem and progenitor
      cells residing in the subventricular region of the postnatal brain. With the aim
      to induce postnatal generation of striatal neurons, we ectopically expressed
      Islet-1, a LIM homeodomain transcription factor expressed by striatal progenitors
      during development, in cells of the subventricular zone (SVZ) of neonatal and
      adult rats. Ectopic expression of Islet-1 in the neonatal, but not adult, SVZ
      resulted in the appearance of a population of cells in the striatum. These cells
      were primarily located in the ventrolateral area of the striatum where they
      differentiate into Ng2 expressing cells. However, no neurogenesis was observed in
      the striatum, nor was ectopic striatal differentiation observed in any other area
      of the brain after retroviral expression of Islet-1 in the SVZ. Thus, although
      ectopic expression of Islet-1 is sufficient to direct the migration of cells into
      the striatum in neonatal animals, it does not specify a striatal projection
      neuron phenotype in cells generated from the SVZ after birth.

PMID- 16806176
TI  - Immune-mediated neuroprotection of axotomized mouse facial motoneurons is
      dependent on the IL-4/STAT6 signaling pathway in CD4(+) T cells.
AB  - The CD4(+) T lymphocyte has recently been found to promote facial motoneuron
      (FMN) survival after nerve injury. Signal Transducer and Activator of
      Transcription (STAT)4 and STAT6 are key proteins involved in the CD4(+) T cell
      differentiation pathways leading to T helper type (Th)1 and Th2 cell development,
      respectively. To determine which CD4(+) T cell subset mediates FMN survival, the
      facial nerve axotomy paradigm was applied to STAT4-deficient (-/-) and STAT6-/-
      mice. A significant decrease in FMN survival 4 weeks after axotomy was observed
      in STAT6-/- mice compared to wild-type (WT) or STAT4-/- mice. Reconstituting
      STAT6-/- mice with CD4(+) T cells obtained from WT mice promoted WT levels of FMN
      survival after injury. Furthermore, rescue of FMN from axotomy-induced cell death
      in recombination activating gene (RAG)-2-/- mice (lacking T and B cells) could be
      achieved only by reconstitution with CD4(+) T cells expressing functional STAT6
      protein. To determine if either the Th1 cytokine, interferon-gamma (IFN-gamma) or
      the Th2 cytokine IL-4 is involved in mediating FMN survival, facial nerve axotomy
      was applied to IFN-gamma-/- and IL-4-/- mice. A significant decrease in FMN
      survival after axotomy occurred in IL-4-/- but not in IFN-gamma-/- mice compared
      to WT mice, indicating that IL-4 but not IFN-gamma is important for FMN survival
      after nerve injury. In WT mice, intracellular IFN-gamma vs. IL-4 expression was
      examined in CD4(+) T cells from draining cervical lymph nodes 14 days after
      axotomy, and substantial increase in the production of both CD4(+) effector T
      cell subsets was found. Collectively, these data suggest that STAT6-mediated
      CD4(+) T cell differentiation into the Th2 subset is necessary for FMN survival.
      A hypothesis relevant to motoneuron disease progression is presented.

PMID- 16806177
TI  - Does excitotoxic cell death of motor neurons in ALS arise from glutamate
      transporter and glutamate receptor abnormalities?

PMID- 16806178
TI  - Dynamic changes in CA1 dendritic spines associated with ischemic tolerance.
AB  - Hippocampal CA1 neurons are particularly vulnerable to 5-10 min durations of
      global ischemia. These cells can develop tolerance to ischemia through prior
      exposure to brief episodes of ischemia (ischemic preconditioning, IP). Dendritic
      spines are implicated in various forms of neuroplasticity including memory and
      recovery of function. Here we characterized the changes in hippocampal CA1
      dendritic spines during the development of ischemic tolerance and the subsequent
      postischemic recovery period. Gerbils received 5 min, bilateral carotid artery
      occlusions preceded by two 1.5 min occlusions each of which were 24 h apart
      (tolerance groups). Spine densities were calculated from CA1 apical and basilar
      dendrites in tolerant animals that survived 3 (IP3), 10 (IP10) or 30 (IP30) days
      as well as sham-operated animals and those that received only the two
      preconditioning episodes (PO). Habituation to a novel open-field was assessed 3,
      7, 10 and 30 days after ischemia to gauge CA1 functional integrity. Dendritic
      spines were quantified from Golgi-Cox stained sections of the CA1 subfield. IP10,
      IP30 and PO animals had significantly higher CA1 basilar and apical spine
      densities than all other groups. Tolerant animals initially displayed open-field
      habituation impairments at a time when spine densities were reduced. Behavioral
      impairments gradually subsided over time in coincidence with an increase in CA1
      spine densities. These findings suggest that dendritic spines may play a role in
      recovery of function associated with ischemic tolerance and stroke.

PMID- 16806179
TI  - Blood-borne factors inhibit Alzheimer's beta-amyloid fibril formation in vitro.
AB  - Soluble amyloid beta-protein (Abeta) does not aggregate to beta-amyloid fibrils
      (fAbeta) in the brain of normal humans. We recently found that the cerebrospinal
      fluid (CSF) from non-Alzheimer's disease (AD) subjects inhibited the formation of
      fAbeta(1-40) and fAbeta(1-42) more strongly than that from AD subjects, although
      the CSF obtained from both groups inhibited the fAbetas formation in vitro. Here,
      we examined the influence of plasma obtained from AD, non-AD and healthy control
      (CTL) subjects on the formation of fAbeta(1-40) and fAbeta(1-42) in vitro.
      Although the plasma obtained from all groups inhibited the formation of fAbeta(1
      40) and fAbeta(1-42), the plasma from non-AD and CTL subjects inhibited the
      formation of fAbetas more strongly than that from AD subjects. These results
      indicate that the plasma as well as CSF in AD would provide a molecular
      environment favorable for fAbeta formation, suggesting a decrease of specific
      inhibitory factors and/or increase of specific accelerating factors.

PMID- 16806180
TI  - Wld(S) mice are protected against the Parkinsonian mimetic MPTP.
AB  - The progressive loss of the nigrostriatal pathway is a distinguishing feature of
      Parkinson's disease. Because terminal field loss appears to precede cell body
      loss, we tested whether the mouse mutant Wld(S), which delays axonal degeneration
      in a variety of disorders, would ameliorate nigrostriatal degeneration following
      treatment with the Parkinsonian mimetic 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). The present findings show that the Wld(S) gene product
      enhances survival, prevents nigrostriatal axon degeneration, and attenuates
      neurotransmitter loss but does not rescue cell bodies. As MPTP is thought to
      impair mitochondrial energy production, these data suggest that disease pathology
      due to metabolic dysfunction could be improved by the Wld(S) gene product. These
      results suggest new therapeutic avenues for Parkinson's disease.

PMID- 16806181
TI  - Reorganization of the rat cerebellar cortex during postnatal development
      following cisplatin treatment.
AB  - We examined the effects of the antitumor agent cisplatin on the development and
      plasticity of cerebellar cytoarchitecture. Since knowledge of the parallel and
      climbing fiber-Purkinje cell system is important in order to determine the
      architectural basis of cerebellar function, we used immunofluorescence for
      vesicular glutamate transporters (VGluT1 and VGluT2) to evaluate the trend of
      synaptogenesis of parallel and climbing fibers on Purkinje cells in the
      cerebellum vermis after a single injection of cisplatin to 10-day-old rats, i.e.,
      during a crucial period of cerebellar development. The temporal and spatial
      patterns of VGluT1 and VGluT2 immunoreactivity after the early cisplatin injury
      provided evidence that remodeling of excitatory afferents and Purkinje cell
      dendrites occurs. After an early slow down of Purkinje cell dendrite growth, 7
      days following the treatment, the extension of the molecular layer was reduced,
      as was parallel fiber innervation, but VGluT1 immunoreactive fibers contacted
      Purkinje cell dendrite branches extending within the external granular layer.
      VGluT2 immunopositive climbing fiber varicosities were still largely present on
      the soma and stem dendrites of Purkinje cells. Twenty days after the cisplatin
      injection, the thickness of the VGluT1 immunopositive molecular layer was
      reduced. VGluT2 climbing fiber varicosities were found on the remodeled Purkinje
      cell dendrites, as in controls, although at a lower density. Alterations in the
      immunoreactivity for polysialic acid neural cell adhesion molecule (PSA-NCAM)
      during the recovery phase suggest that this molecule plays a fundamental role not
      only during development, but also in the reorganization of neuroarchitecture. The
      changes were restricted to the neocerebellar vermis and were likely dependent on
      the different timing of lobule formation. The results of these investigations
      reveal the existence of vulnerability windows of the cerebellum to exposure to
      experimental or environmental cytotoxic agents during a critical period in
      development.

PMID- 16806182
TI  - Spinal cord injury-specific depression of monosynaptic spinal reflex transmission
      by l-5-hydroxytryptophan results from loss of the 5-HT uptake system and not 5-HT
      receptor supersensitivity.
AB  - We studied changes in the spinal segmental reflex and serotonergic (5-HT)
      responses in rats after spinal cord injury (SCI) produced by the weight-dropping
      method at the T8 level. The spinal monosynaptic reflex amplitude (MSR) was
      recorded from the L5 ventral root following stimulation of the ipsilateral L5
      dorsal root. The 5-HT precursor l-5-hydroxytryptophan (L-5-HTP) depressed MSR in
      the spinal cord injured rats but not in normal rats. We investigated whether the
      SCI-specific depression of MSR by L-5-HTP was attributable to postsynaptic
      supersensitivity of 5-HT receptors or presynaptic loss of the 5-HT uptake system.
      Sumatriptan, a selective 5-HT(1B/1D) receptor agonist that is not taken up by 5
      HT transporters, depressed the MSR similarly in both SCI and normal rats,
      suggesting that SCI resulted in the loss of 5-HT terminals and not postsynaptic
      supersensitivity of 5-HT receptors.

PMID- 16806183
TI  - On the move to stimulate cell plasticity in the substantia nigra in Parkinson's
      disease.

PMID- 16806184
TI  - Reduced expression of endothelin B receptors and mechanical hyperalgesia in
      experimental chronic diabetes.
AB  - Diabetic neuropathy is one of the major complications of diabetes mellitus. Small
      nerve fibers degenerate early in the disease, leading to symptoms ranging from
      hyperalgesia to loss of pain and temperature sensation. However, the cellular and
      molecular mechanisms responsible for abnormal pain perception in diabetes have
      not been identified. Both type-A and type-B endothelin receptors (ETAR and ETBR,
      respectively) are present in sensory nerves and appear to regulate neuropathic
      and inflammatory pain. In this study, we compared the expression of endothelin
      receptors and nociceptive responses in normal and experimentally diabetic rats.
      Diabetic animals exhibited both an increase in the withdrawal responses to high
      threshold stimuli (mechanical hyperalgesia) and to light touch stimuli (tactile
      allodynia). Immunohistochemical and Western blot analysis revealed that diabetic
      rats have significantly reduced expression of ETBR in sciatic nerves, while no
      changes were observed in dorsal root ganglia (DRG). In contrast, the expression
      of ETAR in either sciatic nerves or DRG of diabetic rats was not altered.
      Importantly, ETBR-deficient transgenic rats showed alterations in pain perception
      similar to those observed in diabetic rats. These results suggest that changes in
      the expression of ETBR in peripheral nerve may contribute to the development of
      mechanical hyperalgesia and tactile allodynia in chronic diabetes.

PMID- 16806185
TI  - Intraspinal administration of an antibody against CD81 enhances functional
      recovery and tissue sparing after experimental spinal cord injury.
AB  - We previously demonstrated that the tetraspanin protein CD81 is up-regulated by
      astrocytes and microglia after traumatic spinal cord injury in rats and that CD81
      is involved in adhesion and proliferation of cultured astrocytes and microglia.
      Since these reactive glial cells contribute to secondary damage and glial scar
      formation, we studied the effect of local administration of an anti-CD81 antibody
      in experimental spinal cord injury. Adult rats were subjected to a moderate
      spinal cord contusion injury and treated for 2 weeks with different doses of the
      anti-CD81 antibody AMP1 (0.5-5 microg/h) or non-immune IgG (5.0 microg/h). A
      technique was developed to infuse the antibodies directly into the lesion site
      via an intraspinal cannula connected to a pump. Functional recovery was monitored
      during 8 postoperative weeks by means of the Basso, Beattie and Bresnahan (BBB)
      locomotor rating scale, the BBB subscore and Grid-walk test. At the end of the
      study, quantitative histology was performed to assess tissue sparing. Our data
      showed that by itself cannulation of the lesion site resulted in minimal
      functional and histological impairments. Application of 0.5 microg/h AMP1
      resulted in a marked functional recovery (BBB 2 points; Grid-walk 30% less errors
      compared to control). This recovery was accompanied by an 18% increase in tissue
      sparing at the lesion epicentre. No gross histological changes in glial scarring
      were apparent. Our data demonstrate beneficial effects of an anti-CD81 antibody
      on functional recovery in spinal cord injured rats and suggest that this effect
      is mediated through a reduction in secondary tissue loss.

PMID- 16806186
TI  - Oxidative stress in the brain at early preclinical stages of mouse scrapie.
AB  - Oxidative stress has been shown to be involved in the pathogenesis of
      neurodegenerative diseases including prion diseases. Although a growing body of
      evidence suggests direct involvement of oxidative stress in the pathogenesis of
      prion diseases, it is still not clear whether oxidative stress is a causative
      early event in these conditions or a secondary phenomenon commonly found in the
      progression of neurodegenerative diseases. Using a mouse scrapie model, we
      assessed oxidative stress in the brain at various stages of the disease
      progression and observed significantly increased concentration of lipid
      peroxidation markers, malondialdehyde and 4-hydroxyalkenals, and mRNA level of an
      oxidative stress response enzyme, heme oxygenase-1, at early preclinical stages
      of scrapie. The changes preceded dramatic synaptic loss demonstrated by
      immunohistochemical staining of a synaptic protein, synaptophysin. These findings
      imply that the brain undergoes oxidative stress even from an early stage of prion
      invasion into the brain. Given the well-known deleterious effects of reactive
      oxygen-species-mediated damage in the brain, it is considered that the oxidative
      stress at the preclinical stage of prion diseases may predispose the brain to
      neurodegenerative mechanisms that characterize the diseases.

PMID- 16806187
TI  - Role of heat shock response and Hsp27 in mutant SOD1-dependent cell death.
AB  - The fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS) is
      characterized by selective loss of motor neurons and mutations in the copper-zinc
      superoxide dismutase (SOD1) enzyme underlie one form of familial ALS. The
      pathogenic mechanism of these mutations is elusive but is thought to involve
      oxidative stress and protein aggregation. These two phenomena are known to induce
      heat shock proteins (Hsps) which protect stressed cells through their chaperoning
      and anti-apoptotic activity. In order to investigate the role of Hsp27 in mutant
      SOD1-dependent cell death, we used mutant and wild type SOD1 overexpressing N2a
      mouse neuroblastoma cells. Mutant SOD1-dependent cell death could be induced by
      heat shock, and by treating the cells with cyclosporine A or lactacystin.
      Transfection with an Hsp27 expression construct did not protect the N2a cells
      against mutant SOD1-dependent cell death. However, pre-conditioning N2a cells
      with a mild heat shock was accompanied by a significant upregulation of Hsp27 in
      the mutant SOD1 cells, and protected these cells against subsequent cell death
      induced by a more severe heat shock. Selective inhibition of the Hsp27
      upregulation, through the use of Hsp27 siRNA, did not attenuate the protective
      effect of this treatment. These results show that activation of the heat shock
      response protects cells against mutant SOD1-dependent cell death, but that Hsp27
      is not an essential component of the stress response leading to protection.

PMID- 16806188
TI  - The effects by neuroleptics, antimycotics and antibiotics on disulfide reducing
      enzymes from the human pathogens Acanthamoeba polyphaga and Naegleria fowleri.
AB  - This paper discusses the effects of two neuroleptic agents, chlorpromazine and
      trifluoperazine; three antimycotics, amphotericin B, ketoconazole and miconazole
      and four antibiotics, pentamidine, rifampicin, mepacrine and metronidazole on the
      NADPH-dependent disulfide reducing enzymes cystine reductase (CysR), glutathione
      reductase (GR) trypanothione reductase (TR) and a putative disulfide reductase
      for compound X in Acanthamoeba polyphaga from the human pathogens A. polyphaga
      and Naegleria fowleri. Against A. polyphaga, all nine drugs studied had the
      capacity to inhibit the putative disulfide reductase from the trophozoites at a
      concentration of 32microg/ml during a 24h incubation and they were: the
      neuroleptics trifluoperazine (100%) and chlorpromazine (96%), the antimycotics
      miconazole (89%) ketoconazole (81%) and amphotericin B, (53%) and the antibiotics
      pentamidine (89%), rifampicin (64%), mepacrine (57%) and metronidazole (14%).
      Only six of the nine drugs simultaneously inhibited CysR, GR and the putative
      disulfide reductase. In N. fowleri, the most potent inhibitors of trypanothione
      reductase were amphotericin B and miconazole which inhibited 100% at a
      concentration of 32microg/ml during the 24h incubation followed by the
      neuroleptics trifluoperazine (92%) and chlorpromazine (80%) and the antibiotic
      mepacrine (70%). All these also inhibited CysR and GR from the trophozoites other
      than mepacrine which inhibited only CysR and TR. Ketoconazole, rifampicin (which
      did not affect CysR), pentamidine and metronidazole had opposite effects since
      they did not inhibit but increased the amount of the three thiols.

PMID- 16806189
TI  - Cryptosporidium species: preliminary descriptions of the prevalence and genotype
      distribution among school children and hospital patients in the Venda region,
      Limpopo Province, South Africa.
AB  - In the present study, the prevalence and species distribution of Cryptosporidium
      among school children and hospital patients in the Venda region of South Africa
      was determined. Real time PCR (qPCR) was used for initial screening to detect
      positive samples while a nested PCR followed by restriction fragment length
      polymorphism was used to determine the species genotype. From a total of 244
      stool samples tested, 44 (18%) had Cryptosporidium with no significant difference
      (chi(2)=0.04; P=0.841) between samples collected from patients attending
      hospitals 36/197 (18%) and the samples from primary schools 8/47 (17%). The age
      groups most affected were those from 2 to 5 years old (28.6%) and 50 to 59 years
      old (50.0%). Cryptosporidium was detected in 4 (12.5%) of the 31 HIV positive
      individuals. Fifty-seven percent of the Cryptosporidium positive samples were
      diarrheic and 26 (59.1%) had elevated lactoferrin content. C. hominis (82%) was
      more common than C. parvum (18%). This study has demonstrated the high prevalence
      of Cryptosporidium infections in the Venda region and its implications in causing
      diarrhea and inflammation.

PMID- 16806190
TI  - Fundamental research is the basis for understanding and treatment of many human
      diseases.
AB  - There are numerous examples of how fundamental research has been required to
      understand and treat human disease. This article focuses on three human diseases
      of lipid metabolism in which advancements in understanding and treatment would
      not have been possible without basic research. Fabry disease is an inherited
      metabolic disorder caused by the lack of a specific enzyme in glycosphingolipid
      catabolism. Cardiovascular disease is a complex and multifactorial disease but as
      many as half of the cases can be attributed to abnormal levels of plasma
      cholesterol. The incidence of liver disease is increasing due to the current
      epidemic of obesity. It is only recently that curiosity-driven research has
      yielded valuable insight into the mechanism by which liver disease evolves.

PMID- 16806191
TI  - Interleukin-1 stimulated activation of the COT catalytic subunit through the
      phosphorylation of Thr290 and Ser62.
AB  - The protein kinase COT/Tpl2 is activated by interleukin-1 (IL-1), TNFalpha and
      lipopolysaccharide, and its activation by these agonists involves the IkappaB
      kinase beta (IKKbeta) catalysed phosphorylation of the p105 regulatory subunit.
      Here, we show that COT activation also requires catalytic subunit
      phosphorylation, since IL-1beta induced a 5-10-fold activation of a COT mutant
      unable to bind p105. Activation was paralleled by the phosphorylation of Thr290
      and Ser62 and unaffected by the IKKbeta inhibitor PS1145 at concentrations which
      prevented the degradation of IkappaBalpha. Mutagenesis experiments indicated that
      COT activation is initiated by Thr290 phosphorylation catalysed by an IL-1
      stimulated protein kinase distinct from IKKbeta, while Ser62 phosphorylation is
      an autophosphorylation event required for maximal activation.

PMID- 16806192
TI  - Wolfram syndrome-associated mutations lead to instability and proteasomal
      degradation of wolframin.
AB  - Wolfram syndrome is caused by mutations in WFS1 encoding wolframin, a polytopic
      membrane protein of the endoplasmic reticulum. Here, we investigated the
      molecular pathomechanisms of four missense and two truncating mutations in WFS1.
      Expression in COS-7 cells as well as direct analysis of patient cells revealed
      that WFS1 mutations lead to drastically reduced steady-state levels of wolframin.
      All mutations resulted in highly unstable proteins which were delivered to
      proteasomal degradation. No wolframin aggregates were found in patient cells
      suggesting that Wolfram syndrome is not a disease of protein aggregation. Rather,
      WFS1 mutations cause loss-of-function by cellular depletion of wolframin.

PMID- 16806193
TI  - Prior exposure to restraint stress enhances 7,12-dimethylbenz(a)anthracene (DMBA)
      induced DNA damage in rats.
AB  - Over the years, several lines of evidence have emerged supporting the role of
      stress in the development and progression of cancer. Stress can cause an increase
      in the production of reactive oxygen species (ROS) and decrease in the in vivo
      antioxidant defense systems. A ROS-induced DNA damage in peripheral lymphocytes,
      liver and skin cells may be revealed by Comet assay. To test whether DNA is
      damaged by stress/DMBA/stress and DMBA, rats were exposed to multiple doses of
      DMBA in the presence and absence of restraint stress, and DNA damage was
      evaluated. Insignificant differences were detected in all the three cells tested
      (peripheral lymphocytes, liver and skin cells) between control and stress
      treatment in terms of frequencies of damaged DNA. The extent of DNA migration was
      enhanced in DMBA treated rats in a dose dependent manner. Pre-stress DMBA
      treatment showed still higher frequencies of damage in comparison with control,
      stress alone or DMBA alone groups. Thus, prior exposure to stress clearly
      enhanced the DMBA induced DNA damage, especially so in the skin cells (target
      organ of the carcinogen application) than liver and peripheral lymphocytes as
      observed on the basis of the extent of DNA migration (tail DNA) during single
      cell gel electrophoresis.

PMID- 16806194
TI  - Proteasome response to interferon-gamma is altered in senescent human
      fibroblasts.
AB  - We have investigated immunoproteasomes in human fibroblasts during replicative
      senescence. Unlike levels of constitutive proteasome catalytic subunits and 26S
      proteasome regulatory subunits, levels of immunosubunits did not decrease
      dramatically in senescent cells. However, the induction of immunosubunits by
      interferon-gamma (IFN-gamma) was lost in senescent cells. In contrast, levels of
      the 11S proteasome regulator, PA28, were increased by IFN-gamma even in senescent
      cells, and both immunosubunits and PA28 increased with the reversible growth
      arrest in confluent cell cultures. The results highlight differences in the
      mechanisms of regulation of immunoproteasomes compared to constitutive
      proteasomes and in the irreversible growth arrest of senescent cells compared to
      reversible contact-induced growth arrest.

PMID- 16806195
TI  - Introgression of a novel salt-tolerant L-myo-inositol 1-phosphate synthase from
      Porteresia coarctata (Roxb.) Tateoka (PcINO1) confers salt tolerance to
      evolutionary diverse organisms.
AB  - We have previously demonstrated that introgression of PcINO1 gene from Porteresia
      coarctata (Roxb.) Tateoka, coding for a novel salt-tolerant L-myo-inositol 1
      phosphate synthase (MIPS) protein, confers salt tolerance to transgenic tobacco
      plants (Majee, M., Maitra, S., Dastidar, K.G., Pattnaik, S., Chatterjee, A.,
      Hait, N.C., Das, K.P. and Majumder, A.L. (2004) A novel salt-tolerant L-myo
      inositol-1-phosphate synthase from Porteresia coarctata (Roxb.) Tateoka, a
      halophytic wild rice: molecular cloning, bacterial overexpression,
      characterization, and functional introgression into tobacco-conferring salt
      tolerance phenotype. J. Biol. Chem. 279, 28539-28552). In this communication we
      have shown that functional introgression of the PcINO1 gene confers salt
      tolerance to evolutionary diverse organisms from prokaryotes to eukaryotes
      including crop plants albeit to a variable extent. A direct correlation between
      unabated increased synthesis of inositol under salinity stress by the PcINO1 gene
      product and salt tolerance has been demonstrated for all the systems pointing
      towards the universality of the application across evolutionary divergent taxa.

PMID- 16806196
TI  - Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its
      reversal by Memantine.
AB  - The activity of protein phosphatase (PP)-2A, which regulates tau phosphorylation,
      is compromised in Alzheimer disease brain. Here we show that the transient
      transfection of PC12 cells with inhibitor-2 (I2PP2A) of PP2A causes abnormal
      hyperphosphorylation of tau at Ser396/Ser404 and Ser262/Ser356. This
      hyperphosphorylation of tau is observed only when a sub-cellular shift of I2PP2A
      takes place from the nucleus to the cytoplasm and is accompanied by cleavage of
      I2PP2A into a 20 kDa fragment. Memantine, an un-competitive inhibitor of N-methyl
      D-aspartate receptors, inhibits this abnormal phosphorylation of tau and cell
      death and prevents the I2PP2A-induced inhibition of PP2A activity in vitro. These
      findings demonstrate novel mechanisms by which I2PP2A regulates the intracellular
      activity of PP2A and phosphorylation of tau, and by which Memantine modulates
      PP2A signaling and inhibits neurofibrillary degeneration.

PMID- 16806197
TI  - The role of the N-terminal domain of chloroplast targeting peptides in organellar
      protein import and miss-sorting.
AB  - We have analysed 385 mitochondrial and 567 chloroplastic signal sequences of
      proteins found in the organellar proteomes of Arabidopsis thaliana. Despite
      overall similarities, the first 16 residues of transit peptides differ
      remarkably. To test the hypothesis that the N-terminally truncated transit
      peptides would redirect chloroplastic precursor proteins to mitochondria, we
      studied import of the N-terminal deletion mutants of ELIP, PetC and Lhcb2.1. The
      results show that the deletion mutants were neither imported into chloroplasts
      nor miss-targeted to mitochondria in vitro and in vivo, showing that the entire
      transit peptide is necessary for correct targeting as well as miss-sorting.

PMID- 16806198
TI  - Development of glutathione-coupled cantilever for the single-molecule force
      measurement by scanning force microscopy.
AB  - The accuracy and the fidelity of a single-molecule force measurement largely rely
      on how the molecule of interest is attached to the solid substrate surface (bead,
      cantilever, cover glass and etc.). A site-specific attachment of a protein
      without affecting its structure and enzymatic function has been a major concern.
      Here, we established a glutathione-coupled cantilever to which any glutathione S
      transferase (GST)-fused proteins can be attached in a desired direction. The
      rupture force between glutathione and GST was approximately 100 pN on average. By
      using this cantilever, we succeeded in measuring the interaction force between
      importin alpha and importin beta.

PMID- 16806199
TI  - Tumor necrosis factor-alpha and interleukin-1beta increases CTRP1 expression in
      adipose tissue.
AB  - CTRP1, a member of the CTRP superfamily, consists of an N-terminal signal peptide
      sequence followed by a variable region, a collagen repeat domain, and a C
      terminal globular domain. CTRP1 is expressed at high levels in adipose tissues of
      LPS-stimulated Sprague-Dawley rats. The LPS-induced increase in CTRP1 gene
      expression was found to be mediated by TNF-alpha and IL-1beta. Also, a high level
      of expression of CTRP1 mRNA was observed in adipose tissues of Zucker diabetic
      fatty (fa/fa) rats, compared to Sprague-Dawley rats in the absence of LPS
      stimulation. These findings indicate that CTRP1 expression may be associated with
      a low-grade chronic inflammation status in adipose tissues.

PMID- 16806200
TI  - Discrimination between the activity of protein kinase CK2 holoenzyme and its
      catalytic subunits.
AB  - The acronym CK2 denotes a highly pleiotropic Ser/Thr protein kinase whose over
      expression correlates with neoplastic growth. A vexed question about the
      enigmatic regulation of CK2 concerns the actual existence in living cells of the
      catalytic (alpha and/or alpha') and regulatory beta-subunits of CK2 not assembled
      into the regular heterotetrameric holoenzyme. Here we take advantage of novel
      reagents, namely a peptide substrate and an inhibitor which discriminate between
      the holoenzyme and the catalytic subunits, to show that CK2 activity in CHO cells
      is entirely accounted for by the holoenzyme. Transfection with individual
      subunits moreover does not give rise to holoenzyme formation unless the catalytic
      and regulatory subunits are co-transfected together, arguing against the
      existence of free subunits in CHO cells.

PMID- 16806201
TI  - GRP78-binding protein regulates cAMP-induced glial fibrillary acidic protein
      expression in rat C6 glioblastoma cells.
AB  - We previously reported that a novel GRP78-binding protein (GBP) is predominantly
      expressed in rat brain and its expression declines through the aging process. To
      characterize its biological function, we established C6 glioblastoma cells that
      stably overexpressed GBP. Stable overexpression of GBP attenuated cAMP-induced
      expression of the glial fibrillary acidic protein (GFAP) gene, which was
      accompanied by a decrease in cAMP-induced signal transducer and activators of
      transcription 3 (STAT3) phosphorylation. Other distinct cAMP-induced events,
      including a transient reduction in extracellular signal-regulated protein kinase
      phosphorylation and a slowdown in cell proliferation, were hardly affected by GBP
      overexpression. Most importantly, treatment with siRNA against endogenous GBP
      markedly downregulated GBP expression in C6 glioblastoma cells, and dramatically
      augmented cAMP-induced GFAP mRNA expression in parallel with hyper
      phosphorylation of STAT3. These results suggest a novel function of GBP in
      regulating GFAP gene expression via STAT3 phosphorylation.

PMID- 16806202
TI  - Mouse adenovirus type 1 attachment is not mediated by the coxsackie-adenovirus
      receptor.
AB  - Common human adenovirus (Ad) vectors are derived from serotype 2 or 5, which use
      the coxsackie-adenovirus receptor (CAR) as their primary cell receptor. We
      investigated the receptor usage of mouse adenovirus type 1 (MAV-1), which in vivo
      is characterized by a pronounced endothelial cell tropism. Alignment of the fiber
      knob sequences of MAV-1 and those of CAR-using adenoviruses, revealed that amino
      acid residues, critical for interaction with CAR, are not conserved in the MAV-1
      fiber knob. Attachment of MAV-1 to Chinese hamster ovary (CHO) cells was not
      increased by stable transfection with mouse CAR, whereas the binding efficiency
      of Ad2 was 20-fold higher in the mouse CAR-transfectant compared to the wild type
      cells. Also, purified fiber knob of Ad5, which is interchangeable with the Ad2
      fiber knob, did not compete with MAV-1 for receptor binding, indicating that MAV
      1 binds to a receptor different from CAR. These results support further
      exploration of an MAV-1-derived vector as a potential vehicle for gene delivery
      to cell types which are not efficiently transduced by human adenovirus vectors.

PMID- 16806203
TI  - Mechanisms of ammonium transport, accumulation, and retention in ooyctes and
      yeast cells expressing Arabidopsis AtAMT1;1.
AB  - Ammonium is a primary source of N for plants, so knowing how it is transported,
      stored, and assimilated in plant cells is important for rational approaches to
      optimise N-use in agriculture. Electrophysiological studies of Arabidopsis
      AtAMT1;1 expressed in oocytes revealed passive, Deltapsi-driven transport of
      NH(4)(+) through this protein. Expression of AtAMT1;1 in a novel yeast mutant
      defective in endogenous ammonium transport and vacuolar acidification supported
      the above mechanism for AtAMT1;1 and revealed a central role for acid vacuoles in
      storage and retention of ammonia in cells. These results highlight the
      mechanistic differences between plant AMT proteins and related transporters in
      bacteria and animal cells, and suggest novel strategies to enhance nitrogen use
      efficiency in agriculture.

PMID- 16806204
TI  - Interaction of FliS flagellar chaperone with flagellin.
AB  - Premature polymerization of flagellin (FliC), the main component of flagellar
      filaments, is prevented by the FliS chaperone in the cytosol. Interaction of FliS
      with flagellin was characterized by isothermal titration calorimetry producing an
      association constant of 1.9x10(7) M-1 and a binding stoichiometry of 1:1.
      Experiments with truncated FliC fragments demonstrated that the C-terminal
      disordered region of flagellin is essential for FliS binding. As revealed by
      thermal unfolding experiments, FliS does not function as an antifolding factor
      keeping flagellin in a secretion-competent conformation. Instead, FliS binding
      facilitates the formation of alpha-helical secondary structure in the chaperone
      binding region of flagellin.

PMID- 16806205
TI  - Use of laparoscopic cytoreductive surgery to treat infertile women with localized
      adenomyosis.
AB  - OBJECTIVE: We report on two infertile women with localized adenomyosis who had
      successful pregnancies after treatment with laparoscopic cytoreductive surgery.
      DESIGN: Case report. SETTING: Tertiary care university hospital. PATIENT(S): Two
      infertile women with localized adenomyosis. INTERVENTION(S): Laparoscopic
      excision of adenomyotic lesion with/without subsequent hypoestrogenic agent was
      performed. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): Hypoestrogenic agent
      with danazol was administered 3 months immediately after surgery in one woman.
      Both women conceived spontaneously at 30 and 21 months after surgery,
      respectively. The pregnancies were uneventful, and healthy infants were delivered
      via cesarean section at term. CONCLUSION(S): Laparoscopic cytoreductive surgery
      can be an alternative treatment to the use of hypoestrogenic agents or
      hysterectomy in women with localized adenomyosis, especially for those who want
      to maintain their fertility and achieve successful pregnancies. Patients may wait
      up to 21 months after surgery until a pregnancy occurs.

PMID- 16806206
TI  - Single nucleotide polymorphism in exon 17 of the insulin receptor gene is not
      associated with polycystic ovary syndrome in a Korean population.
AB  - OBJECTIVE: To assess the association between the single nucleotide polymorphism
      of the insulin receptor (INSR) gene and polycystic ovary syndrome (PCOS) in a
      Korean population. DESIGN: Case-control study. SETTING: University-based
      hospital. PATIENT(S): One hundred seventy-four patients with PCOS and 93 healthy
      women as controls. MAIN OUTCOME MEASURE(S): Frequency of three genotypes for
      single nucleotide polymorphism found in exon 17 of INSR gene. RESULT(S): The high
      frequency of the T allele was shown both in patient and control groups. The
      frequency of C allele, which known as a normal allele, was slightly higher in the
      patient group than in the control group. CONCLUSION(S): The C/T polymorphism in
      exon 17 of the INSR gene is not associated with susceptibility of PCOS in a
      Korean population.

PMID- 16806207
TI  - Laparoscopic creation of a neovagina with the laparoscopic Vecchietti operation:
      comparison of two instrument sets.
AB  - OBJECTIVE: To compare safety and effectiveness of two different instrument sets
      for the laparoscopic Vecchietti operation for the creation of a neovagina.
      DESIGN: Descriptive study. SETTING: Tertiary referral center. PATIENT(S): Twenty
      six women with Rokitansky syndrome. Twelve consecutive patients had surgery with
      the kit recently developed by Storz (group 1) and 14 consecutive patients had
      surgery with the original kit of Vecchietti (group 2). INTERVENTION(S):
      Laparoscopic Vecchietti operation and clinical and instrumental follow-up for all
      patients. MAIN OUTCOME MEASURE(S): All the parameters reflecting safety,
      effectiveness, and compliance that were systematically measured for all patients.
      RESULT(S): Patients in group 1 had a wider vagina at device removal and
      experienced less vaginal bleeding than patients in group 2, and the removal of
      the device was simpler. Patients in group 1 had a shorter vagina at device
      removal and retained the device and the Foley catheter for a longer period than
      patients in group 2. Diameter and length of neovagina at 1-month follow-up were
      comparable in the two groups. CONCLUSION(S): The availability of this new
      instrument set represents a small but significant improvement in the creation of
      a neovagina by the laparoscopic Vecchietti operation in women with Rokitansky
      syndrome.

PMID- 16806208
TI  - Bicornuate rudimentary uterine horns with functioning endometrium and complete
      cervical-vaginal agenesis coexisting with ovarian endometriosis: a case report.
AB  - OBJECTIVE: To report a patient with bicornuate rudimentary uterine horns with
      functioning endometrium and complete cervical-vaginal agenesis coexisting with
      ovarian endometriosis. DESIGN: Case report. SETTING: University hospital.
      PATIENT(S): A 37-year-old woman with an extremely rare mullerian anomaly of the
      uterus and vagina coexisting with ovarian endometriosis. INTERVENTION(S):
      Resection of the rudimentary uterine horns with bilateral salpingo-oophorectomy.
      MAIN OUTCOME MEASURE(S): Relief from pelvic pain after the operative procedure.
      RESULT(S): The definite diagnosis and removal of the mullerian anomaly and
      endometriosis foci. CONCLUSION(S): Cyclic pelvic pain since the age of 14 was due
      to cryptomenorrhoea in the presence of the bicornuate rudimentary uterine horns
      with functioning endometrium and cervical-vaginal agenesis. Ovarian endometriosis
      developed as a result. In such cases, invasive procedures, such as laparoscopy or
      laparotomy, should be considered to establish the diagnosis. Removing the
      functioning rudimentary uterine horns just after menarche should prevent the
      development of endometriosis and hematometra.

PMID- 16806209
TI  - Simultaneous bilateral ovarian torsion in the follicular phase after gonadotropin
      stimulation.
AB  - OBJECTIVE: To present and discuss the first report of follicular phase bilateral
      ovarian torsion following a cancelled IVF cycle. DESIGN: Case report. SETTING:
      University-based assisted reproductive technology program. PATIENT(S): A 41-year
      old nulligravid patient on day 3 of her menses following a cancelled IVF cycle.
      INTERVENTION(S): Gonadotropin ovulation induction; laparoscopy with detorsion of
      left and right ovaries; aspiration of cysts. RESULT(S): Ovarian torsion resolved;
      follicular development in the following natural cycle. CONCLUSION(S): This is a
      unique case of simultaneous bilateral ovarian torsion following a cancelled IVF
      cycle and presenting in the ensuing follicular phase. Physicians should be aware
      of this unusual risk related to persistently enlarged ovaries in the cycle
      following gonadotropin stimulation. Furthermore, management of the infertility
      patient should be conservative and focused on ovarian preservation whenever
      feasible. Early surgical intervention can permit reperfusion and salvage of the
      affected adnexa.

PMID- 16806210
TI  - Effect of rosiglitazone on embryonic growth and morphology: a study using a whole
      rat embryo culture model.
AB  - The effects of various concentrations of rosiglitazone on in vitro rat embryo
      growth and morphology during the critical period of organogenesis was evaluated.
      We found that rosiglitazone has no significant effects on growth and morphology
      of in vitro early embryo development, even at very high concentrations.

PMID- 16806211
TI  - Tibolone and estradiol plus norethisterone acetate similarly influence
      endothelium-dependent vasodilatation in healthy postmenopausal women.
AB  - In healthy postmenopausal women, E(2) plus norethisterone acetate (1 mg + 0.5 mg)
      or tibolone (2.5 mg) similarly modify flow-mediated endothelium-dependent
      vasodilatation. The effect is dependent on baseline vasodilator reserve, with low
      values being augmented by either treatment.

PMID- 16806212
TI  - Danazol inhibits aromatase activity of endometriosis-derived stromal cells by a
      competitive mechanism.
AB  - OBJECTIVE: To evaluate the inhibitory effect of danazol on estrogen (E)
      production in endometriosis. DESIGN: Prospective randomized study. SETTING:
      Academic research unit of the department of obstetrics and gynecology in a
      university hospital. PATIENT(S): Thirteen patients with endometriosis.
      INTERVENTION(S): Danazol was added to the culture of endometriosis-derived
      stromal cells or suspensions of microsomes prepared from chocolate cysts. MAIN
      OUTCOME MEASURE(S): The aromatase activities as well as mRNA and protein levels
      of aromatase in endometriosis-derived stromal cells or microsomes of
      endometriosis were examined. RESULT(S): Danazol treatment with a concentration
      greater than 10(-6) M significantly suppressed aromatase activity of
      endometriosis-derived stromal cells under basal and prostaglandin E(2) (PGE(2))
      stimulated conditions. Danazol (10(-5) M) did not affect mRNA and protein levels
      of aromatase. Danazol competitively inhibited aromatase activity (by 1.7 x 10(-6)
      M of calculated Ki and 2.9 x 10(-5) M of Ki') of endometriosis microsomes.
      CONCLUSION(S): Danazol competitively inhibited aromatase activity in
      endometriosis-derived stromal cells without affecting either the mRNA or protein
      levels of aromatase. These results indicate the efficacy of local application of
      danazol to endometriotic lesions.

PMID- 16806213
TI  - A prospective study of early pregnancy loss in humans.
AB  - OBJECTIVE: To test two hypotheses: In spontaneous conceptions, early pregnancy
      loss (EPL) is associated with [1] inadequate luteal (ovarian) P, and/or [2]
      elevated follicular (adrenal) P. DESIGN: A population-based prospective study.
      SETTING: Thirty rural Bolivian communities. PATIENT(S): Women volunteers (n =
      191), 19-40 years old, in stable sexual unions and not using contraception.
      INTERVENTION(S): Collection of serial saliva samples throughout sequential
      ovarian cycles and urine samples during late luteal phases. Collections continued
      throughout pregnancy for each detected conception. MAIN OUTCOME MEASURE(S):
      Occurrence of spontaneous conceptions and subsequent outcomes. Salivary
      concentrations of P. Test for elevated urinary human chorionic gonadotropin
      (hCG). RESULT(S): Luteal (through implantation) P levels were similar in
      pregnancies lost within 5 weeks after conception (EPL; n = 8) and those
      pregnancies that were maintained longer (sustained conceptions, SC; n = 32).
      Follicular P was significantly higher in EPL than in SC. CONCLUSION(S): [1]
      Elevated follicular P was associated with EPL in natural conceptions in healthy
      women. [2] Early pregnancy loss exhibits absolute luteal P levels comparable to
      SC, but lower luteal/follicular P ratios.

PMID- 16806214
TI  - Breast tuberculosis imaging.
AB  - We report unusual magnetic resonance images of breast tuberculosis before and
      after treatment. Magnetic resonance imaging may assess the efficiency of
      treatment of breast tuberculosis.

PMID- 16806215
TI  - Gonadal changes and blood sex steroids levels during natural sex inversion in the
      protogynous Mediterranean red porgy, Pagrus pagrus (Teleostei: Sparidae).
AB  - Changes in gonadal structure and serum levels of sex steroids were investigated
      during natural sex inversion from female to male in reared populations of the
      protogynous Mediterranean red porgy, Pagrus pagrus. Four developmental phases
      were identified by histological observation: female, early transitional (ETr),
      late transitional (LTr), and male phases. At female phase, a few nests of
      spermatogonia were observed at the posterior-ventral part of the gonad mainly in
      females out of the breeding season. At ETr phase, spermatogonial proliferation
      occurred while perinucleolar oocytes showed signs of degeneration. At LTr phase,
      seminiferous lobules were formed and spermatogonial proliferation expanded along
      the ovary which degenerated. All types of male germ cells could be found. At male
      phase, functional testis underwent active spermatogenesis while small ovarian
      remnants associated to fat tissue could be detected. Both 17beta-estradiol (E2)
      and estrone (E1) blood levels were significantly lower in fish at transitional
      and male phases in comparison to breeding females, while levels of 11
      ketotestosterone (11-KT) and testosterone (T) gradually increased in the
      transitional and male phases. In conclusion, the protogynous P. pagrus possess a
      delimited type bisexual gonad with a medio-dorsal ovarian area and a latero
      ventral testicular zone. Sex inversion starts mainly after the female breeding
      season with an active spermatogonial proliferation. The testis tissues develop
      while ovarian tissues regress to disappear completely in the functional male.
      This process is accompanied by a sharp decrease of estrogens levels and a
      progressive increase of androgens levels. The physiological significance of such
      endocrine changes is discussed.

PMID- 16806216
TI  - Social suppression of cortisol in female marmosets: role of luteinizing
      hormone/chorionic gonadotropin.
AB  - Behaviorally subordinate female common marmosets (Callithrix jacchus) undergo
      suppression of ovulation and chronic reductions in basal plasma cortisol
      concentrations. Indirect evidence suggests that hypophyseal chorionic
      gonadotropin (CG; the major pituitary luteinizing gonadotropin in marmosets) may
      elevate cortisol concentrations in female marmosets, and therefore that social
      suppression of CG may contribute to diminution of cortisol in subordinates. To
      test this hypothesis, we determined whether pharmacological inhibition of
      pituitary CG release decreases basal and adrenocorticotropin (ACTH)-stimulated
      cortisol secretion. We characterized cortisol and reproductive hormone
      concentrations in six ovary-intact and six ovariectomized marmosets during long
      term treatment with leuprolide acetate, a gonadotropin-releasing hormone (GnRH)
      agonist, and vehicle. Leuprolide suppressed basal plasma CG concentrations,
      abolished the CG response to exogenous GnRH, and, in intact animals, blocked
      ovarian cyclicity. During treatment with vehicle, plasma cortisol concentrations
      were elevated during the periovulatory phase in intact females, compared to the
      follicular phase, the luteal phase, and ovariectomized females. Leuprolide
      suppressed basal cortisol concentrations of intact females as compared to the
      periovulatory phase, but did not affect basal cortisol in ovariectomized animals
      and did not alter responses to exogenous ACTH. These findings suggest that
      elevations in circulating CG concentrations are associated with elevated cortisol
      concentrations in female marmosets, and that this relationship requires
      simultaneous increases in ovarian hormones that occur only during the
      periovulatory period. Thus, suppression of CG release in anovulatory subordinate
      females may not play an important role in socially induced diminution of
      cortisol.

PMID- 16806217
TI  - Paediatric fractures sustained in Parkour (free running).

PMID- 16806218
TI  - Second-trimester double or triple screening for Down syndrome: a comparison of
      Chinese and Caucasian populations.
AB  - OBJECTIVES: To compare the performance of double screening (measuring maternal
      serum levels of alpha-fetoprotein [AFP] and total beta-human chorionic
      gonadotrophin [hCG] as markers for Down syndrome) with that of triple screening
      (also measuring levels of unconjugated estriol [uE3]) in the second trimester of
      pregnancy, and to compare ethnic variance between Chinese and Caucasian
      populations. METHODS: The study investigated 15096 normal singleton pregnancies
      and 24 pregnancies affected with Down syndrome. Frequency distributions of AFP,
      hCG, and uE3 levels were analyzed. Likelihood ratios (LRs) were calculated using
      the multiple of median value (MoM) of AFP, hCG, and uE3 as variables. After
      multiplying maternal age risk by the LR values for the markers used in double and
      triple screening, the specific risks obtained with double and triple screening
      were estimated. The detection rate (DR) and false-positive rate (FPR) were
      calculated at different cut-off points. The serum markers' levels were also
      compared with those of Caucasian women. RESULTS: The median MoM value of hCG was
      higher in women with affected pregnancies (1.40) than those with unaffected
      pregnancies (1.00). However, the median MoMs of AFP and uE3 (0.79 and 0.68) were
      lower in affected than in unaffected pregnancies. At a FPR of 5%, the detection
      rates reached with double and triple screening were 50% and 66.7%, respectively.
      Ratios of the 3 serum markers' medians to those in a study with Caucasian women
      were 1.06 (range=1.04-1.09) for AFP, 1.14 (range=1.10-1.17) for hCG, and 1.28
      (range=1.23-1.41) for uE3 for the relevant gestational weeks. CONCLUSION: Triple
      screening performed better than double screening in the second trimester. Ethnic
      variance should be taken into account in Down syndrome screening.

PMID- 16806219
TI  - Predictors of psychological well-being amongst Korean immigrants to the United
      States: a structured interview survey.
AB  - BACKGROUND: As international migration becomes a common phenomenon in many
      countries, the health issues of immigrants are becoming an important area of
      concern among health care professionals worldwide. OBJECTIVE: Adopting the stress
      health outcome framework, this study examined risks and resources of both
      positive and negative affect (i.e., happiness and depression) among Korean
      Americans who experienced acculturative and recent life stresses. METHODS:
      Hierarchical multiple regression analyses were performed to examine correlates of
      positive and negative outcomes in the stress process on a final sample of 147
      Korean immigrants from a cross-sectional study. RESULTS: For happiness, lower
      levels of acculturative stress and recent life stress, a greater sense of
      mastery, and greater social support were associated with an increased level of
      happiness. None of the individual characteristics were significant. R(2) for the
      full model was .53. For negative affect, acculturative stress and recent life
      stress explained a significant portion (41%) of the total variance associated
      with depression (R(2)=.51). As with the happiness variable, individual
      characteristics failed to add to the predictiveness of the equation, while sense
      of mastery and social support functioned as significant resources in reducing
      depression. CONCLUSION: Increased mastery and greater social support were
      consistently predictive of greater happiness and less depression. Implications
      for future immigrant research are discussed.

PMID- 16806220
TI  - Nurses' reasoning process during care planning taking pressure ulcer prevention
      as an example. A think-aloud study.
AB  - BACKGROUND: Nurses' clinical reasoning is of great importance for the delivery of
      safe and efficient care. Pressure ulcer prevention allows a variety of aspects
      within nursing to be viewed. OBJECTIVE: The aim of this study was to describe
      both the process and the content of nurses' reasoning during care planning at
      different nursing homes, using pressure ulcer prevention as an example. DESIGN: A
      qualitative research design was chosen. SETTINGS: Seven different nursing homes
      within one community were included. PARTICIPANTS: Eleven registered nurses were
      interviewed. METHOD: The methods used were think-aloud technique, protocol
      analysis and qualitative content analysis. Client simulation illustrating
      transition was used. The case used for care planning was in three parts covering
      the transition from hospital until 3 weeks in the nursing home. RESULT: Most
      nurses in this study conducted direct and indirect reasoning in a wide range of
      areas in connection with pressure ulcer prevention. The reasoning focused
      different parts of the nursing process depending on part of the case. Complex
      assertations as well as strategies aiming to reduce cognitive strain were rare.
      Nurses involved in direct nursing care held a broader reasoning than consultant
      nurses. Both explanations and actions based on older ideas and traditions
      occurred. CONCLUSIONS: Reasoning concerning pressure ulcer prevention while care
      planning was dominated by routine thinking. Knowing the person over a period of
      time made a more complex reasoning possible. The nurses' experience, knowledge
      together with how close to the elderly the nurses work seem to be important
      factors that affect the content of reasoning.

PMID- 16806221
TI  - Protein disulfide isomerase assisted protein folding in malaria parasites.
AB  - In eukaryotes, the formation of protein disulfide bonds among cysteine residues
      is mediated by protein disulfide isomerases and occurs in the highly oxidised
      environment of the endoplasmic reticulum. This process is poorly understood in
      malaria parasites. In this paper, we report the gene isolation, sequence and
      phylogenetic comparisons, protein structure and thioredoxin-domain analyses of
      nine protein disulfide isomerases-like molecules from five species of malaria
      parasites including Plasmodium falciparum and Plasmodium vivax (human),
      Plasmodium knowlesi (simian) and Plasmodium berghei and Plasmodium yoelii
      (murine). Four of the studied protein disulfide isomerases belong to P.
      falciparum malaria and have been named PfPDI-8, PfPDI-9, PfPDI-11 and PfPDI-14,
      based on their chromosomal location. Among these, PfPDI-8 bears the closest
      similarity to a prototype PDI molecule with two thioredoxin domains (containing
      CGHC active sites) and a C-terminal Endoplasmic reticulum retrieval signal, SEEL.
      PfPDI-8 is expressed during all stages of parasite life cycle and is highly
      conserved (82-96% identity at amino acid level) in the other four Plasmodium
      species studied. Detailed biochemical analysis of PfPDI-8 revealed that this
      molecule is a potent oxido-reductase enzyme that facilitated the disulfide
      dependent conformational folding of EBA-175, a leading malaria vaccine candidate.
      These studies open the avenues to understand the process of protein folding and
      secretory pathway in malaria parasites that in turn might aid in the production
      of superior recombinant vaccines and provide novel drug targets.

PMID- 16806222
TI  - A contributory role for activated hepatic stellate cells in the dynamics of
      Schistosoma japonicum egg-induced fibrosis.
AB  - The disease manifestations of schistosomiasis arise from the mammalian host
      mediated type 2 T-helper cell-induced (Th2) fibro-granulomatous inflammatory
      response to eggs trapped within host tissues. Activated hepatic stellate cells
      are well described as the effector cells of hepatic fibrosis in a variety of
      human diseases and rodent models. The aim of this study was to further understand
      the mechanism of fibrosis and the role of hepatic stellate cells in hepatic
      schistosomiasis progression. Groups of female CBA mice, which produce an
      intermediate degree of Schistosoma japonicum-induced liver fibrosis, were
      infected with S. japonicum, perfused at fortnightly time points and the liver
      tissue and contained egg granulomas examined by immunohistochemistry and cytokine
      and chemokine analysis using quantitative PCR. Immunohistochemistry demonstrated
      the presence of activated hepatic stellate cells in the periphery of egg
      granulomas, adjacent to fibrotic areas. Time course analysis demonstrated that
      the transcription of smooth muscle actin-alpha type 1 collagen, IL-4, IL-13, IL
      13Ralpha2 and tissue inhibitor of metalloproteinase-1 mirrored the initial
      increase and subsequent down-modulation of granuloma diameter in mice. However,
      the transcription of monocyte chemo-attractant protein-1, Regulated upon
      Activation Normal T Cell Expressed and Secreted (RANTES), TNF-alpha, IFN-gamma
      and matrix metalloproteinase-9 paralleled the evolution of the total liver
      disease burden. Transforming growth factor-beta1 transcription did not appear to
      be of biological significance in this mouse model. Immunohistochemical analysis
      of human hepatic granulomas showed close association of smooth muscle actin-alpha
      expressing cells with fibrosis in five available cases of end-stage (advanced)
      schistosomiasis japonica. We conclude that activated hepatic stellate cells play
      a contributory role in the granulomatous, fibrotic process induced by S.
      japonicum eggs, both in the murine model and in human disease.

PMID- 16806223
TI  - Gene expression profiles of some immune relevant genes from skin of susceptible
      and responding Atlantic salmon (Salmo salar L.) infected with Gyrodactylus
      salaris (Monogenea) revealed by suppressive subtractive hybridisation.
AB  - Suppressive subtractive hybridisation was used to examine the genetic basis of
      susceptibility and resistance of the Atlantic salmon (Salmo salar) to
      Gyrodactylus salaris infection. Selected immune relevant genes are listed and two
      genes, for myeloid leukemia differentiation protein (Mcl-1) and opioid growth
      factor receptor (OGFr), obtained from the susceptible salmon library were
      characterised. Both sequences showed high amino acid identity and similarity with
      human and mouse isoforms, and their possible involvement in the response of
      salmon to G. salaris is discussed. Quantitative reverse transcriptase-PCR was
      performed for both genes. Upregulation of Mcl-1 in B1 backcross salmon of the
      susceptible phenotypic category compared with resistant salmon was demonstrated.
      The possible relationship of the salmon Mcl-1 and cytokines (interleukin 1beta)
      in the G. salaris-induced host response is discussed. Potential involvement of
      OGFr in the depletion of mucous cells during prolonged and heavy G. salaris
      infection, via suppression of DNA synthesis and profound decrease in basal cell
      proliferation, is proposed. However, only two of six susceptible fish showed high
      upregulation of OGFr, which might indicate that its expression is localised to
      sites of wounds resulting from a heavy burden of G. salaris.

PMID- 16806224
TI  - Vasa vasorum neovascularization and lesion distribution among different vascular
      beds in ApoE-/-/LDL-/- double knockout mice.
AB  - OBJECTIVE: To increase understanding of the substantial variation in the
      incidence and distribution of atherosclerotic lesions among different vascular
      beds. In view of some evidence that there are different distributions of
      adventitial vasa vasorum (VV) in different vascular beds, and that this
      correlates with lesion formation, we explored this possible linkage in apoE-/
      /LDL-/- double knockout mice, which develop VV at age beyond 16 weeks. METHODS
      AND RESULTS: Samples from the aorta, coronary, pulmonary, carotid, and cerebral
      arteries in apoE-/-/LDL-/- double knockout mice at the age of 16-80 weeks (n=24)
      were scanned by micro-CT. Using those 3D images, we characterized plaque volume,
      vessel luminal diameter and VV luminal volume along the vessels. Results were
      complemented by histology. Advanced atherosclerotic lesions were found in the
      aorta, pulmonary artery and carotid artery. Occluded intramyocardial vessels
      (vessel diameter approximately 0.1mm) with concomitant myocardial infarctions
      were found without any evidence of adventitial VV neovascularization. VV luminal
      volume follows the order: aorta>pulmonary arteries>carotid arteries. VV were only
      observed in atherosclerotic diseased vessels with a lumen diameter>0.4mm. No
      atherosclerotic lesions, and no VV, were observed in cerebral arteries.
      CONCLUSION: The spatial heterogeneity in the development of atherosclerotic
      lesions among different vascular beds is linked to appearance of VV and to vessel
      lumen diameter.

PMID- 16806225
TI  - Gender influence on metabolic syndrome's effects on arterial stiffness and
      pressure wave reflections in treated hypertensive subjects.
AB  - BACKGROUND: In hypertensive subjects, aortic stiffness, an independent predictor
      of cardiovascular (CV) risk, measured from pulse wave velocity (PWV), contributes
      to enhance augmentation index (AI), a marker of the timing and amplitude of wave
      reflections. Whether PWV and AI are correlated and reflect CV risk in
      hypertensive men and women with metabolic syndrome (MS) remains unknown. METHODS:
      In a cohort of 613 (364 males) treated hypertensive subjects with and without MS
      (41% MS) pulse wave analysis was used to determine aortic PWV and carotid AI. CV
      risk was estimated from standard Framingham equations. RESULTS: In females, but
      not in males, aortic PWV was higher in subjects with MS, when compared with those
      without MS (12.7+/-0.3m/s versus 11.1+/-0.4m/s, p<0.001). This result was
      independent of age and blood pressure. Only in females AI was independently
      related to the presence of MS; AI did not differ between subjects with or without
      MS, both males and females. AI did not correlate with PWV, except in males
      without MS. The overall CV risk was strongly associated to PWV independently of
      MS and gender, but AI was associated to CV risk only in males. CONCLUSION: In
      treated hypertensive subjects, the effect of MS on PWV and AI is modulated by
      gender. The dissociation between PWV and AI observed in women with MS was due to
      "blunted" wave reflections. This finding is associated with the fact that PWV,
      but not AI, was a constant marker of CV risk in subjects with MS, whether men and
      women.

PMID- 16806226
TI  - Prediction of genetic risk for metabolic syndrome.
AB  - OBJECTIVES: The aim of the study was to identify gene polymorphisms that confer
      susceptibility to metabolic syndrome in order to allow reliable assessment of
      genetic risk for this condition. METHODS AND RESULTS: The study population
      comprised 1788 unrelated Japanese individuals (1033 men, 755 women), including
      1017 subjects with metabolic syndrome (634 men, 383 women) and 771 controls (399
      men, 372 women). The genotypes for 158 polymorphisms of 133 candidate genes were
      determined with a method that combines the polymerase chain reaction and sequence
      specific oligonucleotide probes with suspension array technology. Multivariable
      logistic regression analysis with adjustment for age, sex, and the prevalence of
      smoking revealed that the -1131T-->C polymorphism of the apolipoprotein A-V gene
      (APOA5) was significantly associated with the prevalence of metabolic syndrome,
      with the C allele representing a risk factor for this condition. A stepwise
      forward selection procedure demonstrated that APOA5 genotype (CC+TC versus TT)
      significantly affected the prevalence of metabolic syndrome. The C allele of this
      polymorphism was associated with an increased serum concentration of
      triglycerides and a decreased concentration of HDL-cholesterol. CONCLUSIONS:
      Genotype for APOA5 may prove reliable for assessment of genetic risk for
      metabolic syndrome.

PMID- 16806227
TI  - Potent free radical scavenger, edaravone, suppresses oxidative stress-induced
      endothelial damage and early atherosclerosis.
AB  - OBJECTIVE: Effects of potent free radical scavenger, edaravone, on oxidative
      stress-induced endothelial damage and early atherosclerosis were investigated
      using animal models and cultured cells. METHODS AND RESULTS: Endothelial
      apoptosis was induced by 5-min intra-arterial exposure of a rat carotid artery
      with 0.01 mmol/L H(2)O(2). Edaravone treatment (10mg/kg i.p.) for 3 days
      suppressed endothelial apoptosis, as evaluated by chromatin staining of en face
      specimens at 24h, by approximately 40%. Similarly, edaravone dose-dependently
      inhibited H(2)O(2)-induce apoptosis of cultured endothelial cells in parallel
      with the inhibition of 8-isoprostane formation, 4-hydroxy-2-nonenal (4-HNE)
      accumulation and VCAM-1 expression. Next, apolipoprotein-E knockout mice were fed
      a high-cholesterol diet for 4 weeks with edaravone (10mg/kg i.p.) or vehicle
      treatment. Edaravone treatment decreased atherosclerotic lesions in the aortic
      sinus (0.18+/-0.01 to 0.09+/-0.01 mm(2), P<0.001) and descending aorta (5.09+/
      0.86 to 1.75+/-0.41 mm(2), P<0.05), as evaluated by oil red O staining without
      influence on plasma lipid concentrations or blood pressure. Dihydroethidium
      labeling and cytochrome c reduction assay showed that superoxide anions in the
      aorta were suppressed by edaravone. Also, plasma 8-isoprostane concentrations and
      aortic nitrotyrosine, 4-HNE and VCAM-1 contents were decreased by edaravone
      treatment. CONCLUSIONS: These results suggest that edaravone may be a useful
      therapeutic tool for early atherosclerosis, pending the clinical efficacy.

PMID- 16806228
TI  - Aerobic exercise and lipids and lipoproteins in children and adolescents: a meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: Use the meta-analytic approach to examine the effects of aerobic
      exercise on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C),
      low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in children
      and adolescents. STUDY DESIGN: Randomized controlled trials which were limited to
      aerobic exercise >or=4 weeks in children and adolescents 5-19 years of age.
      RESULTS: Twelve outcomes representing 389 subjects were available for pooling.
      Using random-effects modeling, a trend for statistically significant decreases of
      12% was found for TG (X +/-S.E.M., -11.0+/-6.1mg/dl; 95% CI, -22.8-0.8 mg/dl)
      with no statistically significant changes for TC, HDL-C, and LDL-C. Decreases in
      LDL-C were associated with increased training intensity (r=-0.89; 99% CI, -0.99
      to -0.04) and older age (r=-0.90; 99% CI, -0.99 to -0.25) while increases in HDL
      C were associated with lower initial HDL-C (r=-0.75; 99% CI, -0.94 to -0.80).
      Statistically significant decreases in TG were observed in overweight/obese
      subjects with a trend for increases in HDL-C (TG, X +/-S.E.M., -23.9+/-7.0mg/dl;
      95% CI, -37.6 to -10.1mg/dl; HDL-C, X +/-S.E.M., 4.0+/-2.3mg/dl; 95% CI, -0.5
      8.5mg/dl). CONCLUSIONS: Aerobic exercise decreases TG in overweight/obese
      children and adolescents.

PMID- 16806229
TI  - Atherogenesis takes place in cholesterol-fed rabbits when circulating
      concentrations of endogenous cortisol are increased and inflammation suppressed.
AB  - Atherosclerosis is an inflammatory disease, but the response of the endogenous
      anti-inflammatory system during this process has not been evaluated previously.
      Cortisol is the end product of this anti-inflammatory system, but is also able to
      activate cellular processes that induce atherogenesis; however, it is unknown
      whether atherogenesis occurs when circulating concentrations of endogenous
      cortisol are increased or when they are decreased. We have evaluated the counter
      regulatory responses of cortisol and interleukin-1beta (IL-1beta) during the
      short- and long-term responses to vascular injury in rabbits fed a 2% cholesterol
      diet. In the short-term group (n=18), serum cortisol and IL-1beta concentrations
      were measured after 10, 20 and 30 days. Rabbits developed hypercholesterolemia
      and hypercortisolemia, with only modest increases in IL-1beta. Although
      inflammation was low-grade, atherogenesis took place, with subintimal lipid
      accumulation evident on day 30. In the second group (n=18), we evaluated
      variables after 40, 60 and 90 days. This group developed hypercholesterolemia,
      but serum cortisol concentrations were inappropriately normal, while IL-1beta
      concentrations were elevated 8.6-fold; advanced atherosclerotic plaques were
      evident on days 60 and 90. These results show that atherogenesis occurs when high
      endogenous cortisol levels are suppressing inflammation, and are consistent with
      a promotion of early atherogenesis by high cortisol concentrations.

PMID- 16806230
TI  - CETP expression enhances liver HDL-cholesteryl ester uptake but does not alter
      VLDL and biliary lipid secretion.
AB  - The aim of this work was to study how CETP expression affects whole body
      cholesterol homeostasis. Thus, tissue uptake and plasma removal rates of labeled
      HDL-cholesteryl ester (CE), VLDL secretion rates, and biliary lipid secretion and
      fecal bile acid content were compared between human CETP transgenic (Tg) and non
      transgenic (nTg) mice fed with a standard diet. CETP Tg mice exhibited increased
      HDL-CE plasma fractional catabolic rate and uptake by the liver, adrenals,
      adipose tissue and spleen. HDL fractions from both CETP Tg and from nTg mice were
      removed faster from the plasma of CETP expressing than from nTg mice, suggesting
      a direct role of CETP in accelerating tissue CE uptake. However, neither hepatic
      output of VLDL cholesterol and triglycerides nor biliary lipid and fecal bile
      acid excretion were changed in CETP Tg compared to nTg mice. CETP Tg mice also
      showed enhanced hepatic cholesterol content. Steady state cholesterol homeostasis
      was probably preserved through the downregulation of hepatic HMG-CoA reductase
      and LDL receptor expression. In conclusion, although CETP expression facilitates
      cholesteryl ester tissue uptake, it does not alter biliary lipid and fecal bile
      acid excretion, the mandatory final step of the reverse cholesterol transport.

PMID- 16806231
TI  - Inflammatory suppression rapidly attenuates microvascular dysfunction in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is associated with greater risk of cardiovascular
      morbidity and mortality, the inflammatory component of RA being strongly linked
      to this excess risk. Endothelial dysfunction is linked to atherosclerosis and has
      been demonstrated in larger vessels in RA. In this pilot study, we determined for
      the first time whether skin microvascular function was impaired in patients with
      active RA and also determined its response to anti-inflammatory treatment. This
      was assessed non-invasively using laser Doppler imaging combined with
      iontophoresis of the vasodilators acetylcholine (ACh, endothelium dependent) and
      sodium nitroprusside (SNP, endothelium independent) to the forearm. Eight RA
      patients admitted for acute flare-ups were assessed before and following anti
      inflammatory treatment. Standard laboratory indices were obtained along with pain
      perception (VAS). A control group of eight subjects was included for baseline
      comparison. Compared to this group, vascular function was substantially and
      significantly (P<0.00001) lower in RA patients. Following treatment, as CRP and
      VAS decreased, vascular function improved for both ACh (P<0.00001) and SNP
      (P=0.001), this improvement being significantly greater for ACh (P<0.001).
      Vascular dysfunction is evident in RA patients, even at the level of the
      cutaneous microcirculation, but improves as inflammation regresses. Assessment of
      cutaneous vascular function may be a useful, non-invasive surrogate indicator of
      vascular risk in RA, inclusive of myocardial microvascular abnormalities.

PMID- 16806232
TI  - Coronary endothelium expresses a pathologic gene pattern compared to aortic
      endothelium: correlation of asynchronous hemodynamics and pathology in vivo.
AB  - Coronary arteries are the most disease prone arteries in the circulation and are
      characterized by unique hemodynamic features, wherein wall shear stress (WSS)
      induced by blood flow and circumferential strain (CS) driven by pressure are
      highly out-of-phase temporally (asynchronous hemodynamics). To investigate
      whether there is a correlation between asynchronous hemodynamics and pathology in
      vivo, we examined endothelial cell (EC) gene expression and nuclear morphology in
      two distinct hemodynamic regions of male New Zealand rabbits: coronary arteries
      (left anterior descending artery cLAD), and aorta (aortic arch inner curvature,
      outer curvature, and straight descending aorta). En face imaging showed strong
      similarities in EC nuclear length:width ratio and angle of orientation in the
      cLAD and aorta. Real-time RT-PCR, however, showed that coronary arteries had
      significantly reduced (>5-fold) eNOS mRNA levels compared to all aortic regions,
      while ET-1 showed an opposite trend ( approximately 2.5-fold). Coronary arteries
      with characteristic asynchronous hemodynamics displayed pro-atherogenic eNOS and
      ET-1 gene expression profiles while the EC nuclei morphology did not differ from
      non-atherogenic regions in the aorta. This study demonstrates a correlation
      between asynchronous hemodynamics and pro-atherogenic gene expression patterns in
      vivo that is induced by hemodynamics inherent to the circulation.

PMID- 16806233
TI  - Identifying leukocyte gene expression patterns associated with plasma lipid
      levels in human subjects.
AB  - Plasma lipid levels have been known to be risk factors for atherosclerosis for
      decades, and in recent years it has become accepted that inflammation is a
      crucial event in the pathogenesis of atherosclerosis. In this study, we
      investigated the relationship between plasma lipids and leukocytes by profiling
      and analyzing leukocyte gene expression in response to plasma lipid levels. We
      discovered several interesting patterns of leukocyte gene expression: (1) the
      expression of a number of immune response- and inflammation-related genes are
      correlated with plasma lipid levels; (2) genes involved in lipid metabolism and
      in the electron transport chain were positively correlated with triglycerides and
      low-density lipoprotein cholesterol (LDL) levels, and negatively correlated with
      high-density lipoprotein cholesterol (HDL) levels; (3) genes involved in platelet
      activation were negatively correlated with HDL levels; (4) transcription factors
      regulating lipogenesis-related genes were correlated with plasma lipid levels;
      (5) a number of genes correlated with plasma lipid levels were found to be
      located in the regions of known quantitative trait loci (QTLs) associated with
      hyperlipemia. Our findings suggest that leukocytes respond to changing plasma
      lipid levels by regulating a network of genes, including genes involved in immune
      response, and lipid and fatty acid metabolism.

PMID- 16806234
TI  - Endothelial progenitor cell mobilization after percutaneous coronary
      intervention.
AB  - BACKGROUND: In animal models, circulating endothelial progenitor cells (EPC) have
      been shown to participate in repair of damaged or degenerating vascular surfaces.
      In humans, reduced EPC counts correlate with cardiovascular risk and disease
      outcome; yet it has been difficult to establish that EPC are in fact mobilized in
      response to vascular injury as a physiologic response. We therefore studied early
      (<12h) mobilization of EPCs into the peripheral circulation after a defined
      vascular manipulation, percutaneous coronary intervention (PCI) in acute coronary
      syndrome (ACS) and non-ACS patients. METHODS AND RESULTS: CD34/CD31 positive EPC
      colony forming units (EPC-CFU) were quantified by a blinded observer in
      peripheral blood samples from eight control patients with angiographically normal
      coronary arteries, and in 30 patients with coronary artery lesions before and 12h
      after PCI. All patients (n=38) had one or more CV risk factors. Ten patients
      presented with acute coronary syndrome (PCI(ACS)), and the rest (n=20) underwent
      elective PCI (PCI(Elect)). Despite the presence of an acute coronary syndrome,
      patients in the PCI(ACS) group did not present with increased EPC-CFU compared
      with either the PCI(Elect) or control groups (P>0.05). In addition, EPC-CFU
      (colonies/ml blood) increased significantly in the PCI(Elect) group after stent
      placement (11.8+1.6 before versus 16.5+1.9 after, P=0.0009), while in contrast,
      PCI did not stimulate EPC mobilization in patients in the PCI(ACS) group (9.6+3.2
      before versus 6.5+1.8, P=0.20). We found a higher presenting vascular endothelial
      growth factor (VEGF) level in the PCI(Elect) group compared to PCI(ACS)
      (78.7+25.2 versus 15.3+7.9 pg/ml blood, P=0.02). However, VEGF levels increased
      after PCI only in the PCI(ACS) group (15.3+7.9 to 133.3+27.5 pg/ml, P=0.003) and
      not in the PCI(Elect) group (78.7+25.2 to 79.7+12.2 pg/ml, P=0.97). CONCLUSION:
      Our findings suggest that focal coronary endothelial injury as a result of PCI
      triggers early mobilization of EPC into the peripheral circulation in patients
      presenting for an elective PCI, without a corresponding rise in VEGF levels. In
      contrast, patients with an acute coronary syndrome fail to respond to PCI with
      early EPC mobilization despite a significant rise in VEGF. The results of the
      present study may suggest a novel mechanism for early EPC augmentation after PCI.

PMID- 16806235
TI  - Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and
      trans-resveratrol in apolipoprotein E deficient mice.
AB  - A strong negative correlation between polyphenols consumption and coronary heart
      disease has been extensively documented. These results prompted investigations on
      the mechanisms responsible for polyphenols effects in cardiovascular disease. The
      aim of this work was to investigate in apoE KO mice the effect of P183/1 (a
      mixture of cathechin, caffeic acid and resveratrol) on atherosclerosis and gene
      expression patterns in the vascular wall. ApoE KO mice were fed a diet
      supplemented with P183/1, 40 and 160 mg/kg body weight/day for 8 weeks. The
      supplementation with the high dose of P183/1 significantly reduced the presence
      of atherosclerotic plaque by 40 and 36% in the aortic sinus and in the ascending
      aorta, respectively. This reduction was associated with a reduced expression of
      markers for macrophages, lymphocytes (both Th1 and Th2) and of MCP-1, MIP-1alpha,
      MIP-1beta, CCR1, CCR2 and ET1 in the vascular wall. In conclusion, P183/1
      supplementation significantly decreases atherosclerosis in ApoE KO mice by
      affecting inflammatory cells recruitment and expression of pro-inflammatory
      chemokines in the vascular wall.

PMID- 16806236
TI  - Artificial composite bone as a model of human trabecular bone: the implant-bone
      interface.
AB  - The use of artificial bones in implant testing has become popular due to their
      low variability and ready availability. However, friction coefficients, which are
      critical to load transfer in uncemented implants, have rarely been compared
      between human and artificial bone, particularly for wet and dry conditions. In
      this study, the static and dynamic friction coefficients for four commercially
      used titanium surfaces (polished, Al(2)O(3) blasted, plasma sprayed, beaded)
      acting on the trabecular component of artificial bones (Sawbones) were compared
      to those for human trabecular bone. Artificial bones were tested in dry and wet
      conditions and normal interface stress was varied (0.25, 0.5, 1.0MPa). Friction
      coefficients were mostly lower for artificial bones than real bone. In
      particular, static friction coefficients for the dry polished surface were 20% of
      those for real bone and 42-61% for the dry beaded surface, with statistical
      significance (alpha<0.05). Less marked differences were observed for dynamic
      friction coefficients. Significant but non-systematic effects of normal stress or
      wet/dry condition on friction coefficients were observed within each surface
      type. These results indicate that the use of artificial bone models for pre
      clinical implant testing that rely on interface load transfer with trabecular
      bone for mechanical integrity can be particularly sensitive to surface finish and
      lubrication conditions.

PMID- 16806237
TI  - Prediction of summation in incompletely fused tetanic contractions of rat muscle.
AB  - Summation is the accumulating contractile force resulting from sequential
      activations applied to a muscle without sufficient interval to permit complete
      relaxation. The purpose of this study was to evaluate summation in the rat medial
      gastrocnemius muscle, and to determine if the contractile responses during
      summation could be predicted from the relationship between force and activation
      pattern. In the first part of this study, the consistency of summation in the rat
      gastrocnemius muscle was assessed and prediction equations were derived. The
      second part compared predicted summation with actual contractions obtained in a
      new set experiments. Summation was assessed by calculation of the contractile
      response, per stimulation, for up to five stimulating pulses at these
      frequencies: 20, 40, 60 and 80Hz. This was done by subtraction of the force
      transient for j-1 pulses of stimulation (where j=1-5 pulses) from the force
      response with j pulses of stimulation. Each of these force differences was
      evaluated for peak rate of force development, contraction time and half
      relaxation time. Contraction and half-relaxation times changed by only a small
      magnitude from values obtained for the twitch. Peak rate of force development was
      proportional to the active force for all force transients obtained by
      subtraction. The force per activation increased from the first to the fifth
      stimulus, and was dependent on interpulse delay. In the second series of
      experiments, the predicted force was related to the actual force for brief
      tetanic contractions at 40, 50 and 60Hz (r(2)=0.875). These experiments
      demonstrate that the force response to sequential activations is consistent and
      predictable. Summation can be predicted, knowing only the amplitude of the twitch
      contraction and the relationship between delay and force for each activating
      stimulus.

PMID- 16806238
TI  - Selectivity in reversed-phase separations Influence of the stationary phase.
AB  - The selectivity difference between 15 different stationary phases was measured
      using a large number of analytes at 2 or 3 different pH values (3, 7 and 10) with
      acetonitrile and methanol as the mobile phase modifiers. The packings discussed
      include standard C(8) and C(18) packings, packings with embedded polar groups, a
      phenyl packing, a pentafluoro-phenyl packing, an adamantylethyl packing and
      others. The major selectivity differences observed are discussed in detail.
      Specific effects such as pi-pi interactions on phenyl packings or hydrogen-bond
      interactions on phases with embedded polar groups are confirmed.

PMID- 16806239
TI  - Novel nylon-supported organic-inorganic hybrid membrane with hierarchical pores
      as a potential immobilized metal affinity adsorbent.
AB  - Chitosan-based porous organic-inorganic hybrid membranes supported by
      microfiltration nylon membranes were prepared, in which gamma
      glycidoxypropyltrimethoxysilane (GPTMS) was used as an inorganic source as well
      as crosslinking reagent. Polyethylene glycol (PEG) with different molecular
      weight and content was used as imprinting molecule for morphology control. In
      situ crosslinking of chitosan and simultaneous polymerization of GPTMS in PEG
      template environment endowed the hybrid membrane with specific characteristics.
      Distinct hybrid effect between chitosan (CS) and GPTMS was revealed by shifting
      in X-ray diffraction (XRD) pattern, decomposition in simultaneous
      thermogravimetry and differential scanning calorimetry (TG/DSC) testing. As
      manifested by scanning electron microscopy (SEM), the molecular weight and
      content of PEG had remarkable effect on the resulting surface morphology of the
      hybrid membrane and a given surface morphology could be obtained by extracting of
      the imprinted PEG molecular. Among three types of porogen used: PEG 400, PEG 4000
      and PEG 20000, only PEG 20000 could result in a porous surface. Moreover, a
      special porous surface with three-dimensional (3D) hierarchical structure-in
      structure pore fashion was obtained when content of PEG 20000 was controlled at
      15%. Experimental results also showed that the hybrid membrane had low swelling
      ratio and high stability in acidic solution. After conveniently coordinated with
      copper ions, the porous metal chelating hybrid membrane could effectively adsorb
      the model protein, bovine serum albumin (BSA). As expected, the hybrid membrane
      imprinted with 15% PEG 20000 had remarkably high copper ion binding and BSA
      adsorption capacity, which might result from the large surface area, high ligand
      density and suitable interconnected 3D hierarchical porous surface.

PMID- 16806240
TI  - Transition from creeping via viscous-inertial to turbulent flow in fixed beds.
AB  - This review is concerned with the analysis of flow regimes in porous media, in
      particular, in fixed beds of spherical particles used as reactors in engineering
      applications, or as separation units in liquid chromatography. A transition from
      creeping via viscous-inertial to turbulent flow is discussed based on macro-scale
      transport behaviour with respect to the pressure drop-flow rate dependence, in
      particular, the deviation from Darcy's law, as well as direct microscopic data
      which reflect concomitant changes in the pore-level hydrodynamics. In contrast to
      the flow behaviour in straight pipes, the transition from laminar to turbulent
      flow in fixed particulate beds is not sharp, but proceeds gradually through a
      viscous-inertial flow regime. The onset of this steady, nonlinear regime and
      increasing role of inertial forces is macroscopically manifested in the failure
      of Darcy's law to describe flow through fixed beds at higher Reynolds numbers.
      While the physical reasons for this failure still are not completely understood,
      it is not caused by turbulence which occurs at Reynolds numbers about two orders
      of magnitude above those for which a deviation from Darcy's law is observed.
      Microscopic analysis shows that this steady, nonlinear flow regime is
      characterized by the development of an inertial core in the pore-level profile,
      i.e., at increasing Reynolds number velocity profiles in individual pores become
      flatter towards the center of the pores, while the velocity gradient increases
      close to the solid-liquid interface. Further, regions with local backflow and
      stationary eddies are demonstrated for the laminar flow regime in fixed beds. The
      onset of local fluctuations (end of laminar regime) is observed at superficial
      Reynolds numbers on the order of 100. Complementary analysis of hydrodynamic
      dispersion suggests that this unsteady flow accelerates lateral equilibration
      between different velocities in fixed beds which, in turn, reduces spreading in
      the longitudial (macroscopic flow) direction.

PMID- 16806241
TI  - Determination of sulfonamides in selected Malaysian swine wastewater by high
      performance liquid chromatography.
AB  - An analytical HPLC method for the simultaneous determination of eight
      sulfonamides in swine wastewater was developed. The samples were collected from
      three states in Malaysia. Sample clean up was carried out by employing solid
      phase extraction using a 60 mg Oasis HLB (Waters) cartridge with 3 ml reservoir.
      The HPLC column used was Supelcosil C18 (250 mm x 4.6mm I.D.) and elution was
      carried out using gradient mode. The mobile phases used were acetonitrile and
      0.5% acetic acid in purified water. Antibiotics were detected using UV absorbance
      at 272 nm. Recoveries obtained for sulphanilamide ranged from 31.9+/-5.1% to
      36.2+/-1.0%, while recoveries for other sulfa drugs studied were from 91.9+/-5.0%
      to 106.0+/-1.1%. The limit of quantitation (LOQ) for sulfamerazine,
      sulfamethazine and sulfamethoxypyridazine was 7.5 ng/L, while the LOQ for the
      other studied antibiotics was 5.0 ng/L. The method was used to analyse
      sulfonamides in wastewater collected from selected Malaysian swine facilities.

PMID- 16806242
TI  - Time distribution of adsorption entropy of gases on heterogeneous surfaces by
      reversed-flow gas chromatography.
AB  - The reversed-flow gas chromatography (RF-GC) technique has been applied to
      measure the adsorption entropy over time, when gaseous pentane is adsorbed on the
      surface of two solids (gamma-alumina and a silica supported rhodium catalyst) at
      393.15 and 413.15K, respectively. Utilizing experimental chromatographic data,
      this novel methodology also permits the simultaneous measurement of the local
      adsorption energy, epsilon, local equilibrium adsorbed concentration, c(s)(*),
      and local adsorption isotherm, theta(p, T, epsilon) in a time resolved way. In
      contrast with other inverse gas chromatographic methods, which determine the
      standard entropy at zero surface coverage, the present method operates over a
      wide range of surface coverage taking into account not only the adsorbate
      adsorbent interaction, but also the adsorbate-adsorbate interaction. One of the
      most interesting observations of the present work is the fact that the
      interaction of n-pentane is spontaneous on the Rh/SiO(2) catalyst for a very
      short time interval compared to that on gamma-Al(2)O(3). This can explain the
      different kinetic behavior of each particular gas-solid system, and it can be
      attributed to the fact that large amounts of n-C(5)H(12) are present on the
      active sites of the Rh/SiO(2) catalyst compared to those on gamma-Al(2)O(3), as
      the local equilibrium adsorbed concentration values, c(s)(*), indicate.

PMID- 16806243
TI  - Future of high pressure liquid chromatography: do we need porosity or do we need
      pressure?
AB  - Making a theoretical study supported by experiments of the kinetic advantages of
      increased inlet pressures versus increased external porosity using impedance
      plots of analysis time versus required plate number, it is found that both
      approaches more or less have the same effect on the kinetic performance. The need
      to change a given system to one with an increased inlet pressure or with an
      increased external porosity can best be assessed from the optimal plate number
      (N(opt)) of the system. When the pursued application requires a plate number that
      is larger than N(opt), any increase in inlet pressure and external porosity is
      beneficial. When the required plate number is smaller than N(opt), any increase
      in inlet pressure and external porosity should preferentially be accompanied by
      an overall reduction of the feature sizes of the support. The degree to which
      this feature size reduction can be realized in practice will to a large extent
      determine which of the two approaches will be the dominant system of the future.

PMID- 16806244
TI  - Development of a novel method based on liquid chromatography-evaporative light
      scattering detection for the direct determination of streptomycin and
      dihydrostreptomycin in raw materials, pharmaceutical formulations, culture media
      and plasma.
AB  - A novel method for the non-derivatization liquid chromatographic determination of
      streptomycin (STR) and dihydrostreptomycin (DHSTR) was developed and validated
      based on evaporative light scattering detection (ELSD). Utilizing a
      ThermoHypersil BetaBasic C18 analytical column, evaporation temperature of 50
      degrees C and pressure of nebulizing gas (nitrogen) of 3.5 bar, the optimized
      mobile phase was 1.25 mL L(-1) TFA aqueous solution, in an isocratic mode at a
      rate of 1.0 mL min(-1). STR was eluted at 5.6 min and DHSTR at 7.8 min with a
      resolution of 4.4. Linear calibration curves were obtained from 2 to 120 microg
      mL(-1) (r > 0.9990) for STR and 2-75 microg mL(-1) (r > 0.9994) for DHSTR, with a
      LOD equal to 0.7 and 0.5 microg mL(-1), respectively. The developed method was
      applied for the assay of STR and DHSTR (sulfate) in pharmaceutical raw materials
      and formulations, while the simultaneous direct determination of sulfate was
      feasible (tR = 2.5 min, LOD = 1.4 microg mL(-1), double logarithmic calibration
      curve in the range of 4-50 microg mL(-1), r > 0.9998). Modified isocratic mobile
      phase (H2O-ACN, 90:10, v/v, containing 1.25 mL L(-1) TFA), was used for the
      determination of streptomycin B impurity in STR sulfate raw material and a
      gradient mobile phase (H2O-ACN containing TFA) was used for the determination of
      DHSTR in the presence of penicillinG procaine. The developed method was also
      applied for the assay of commercial formulations (STR powder and DHSTR injection
      solution and suspension) (%recovery 98-102, %RSD < 1.3, n = 3 x 3), for the
      determination of STR in bacteria culture medium (%recovery 99.6, %RSD = 0.8, n =
      3 x 3), and for the determination of DHSTR in human plasma (2.0-23.0 microg mL(
      1)) after solid phase extraction using carboxylate cartridges (%recovery 98.4
      101.8, %RSD = 3.2, n = 3 x 3).

PMID- 16806245
TI  - Synthesis and determination of dicarboxylic degradation products of nonylphenol
      polyethoxylates by gas chromatography-mass spectrometry.
AB  - The synthesis and determination of persistent dicarboxylic metabolites of
      alkylphenol polyethoxylates (NPEOs), carboxyalkyl phenoxy ethoxy carboxylates
      (CAPECs), are investigated. The synthesized CAPECs have three and four carbon
      atoms and a carboxyl group in the alkyl chain side, and a carboxymethoxy acid
      group in its para-position (expressed as CA(3)P1EC and CA(4)P1EC in their
      abbreviation). The synthesis was successfully accomplished via a four-step
      reaction sequence that started from 4-fluoroanisole. After propylation by a
      propanol/acetyl chloride procedure, the derivatives of synthesized CA(3)P1EC and
      CA(4)P1EC were separated and identified by GC-MS with electron impact ionization
      (EI). The most abundant characteristic ions were produced by benzylic cleavages
      of carboxyalkyl chain to yield [M-87](+), corresponding to ions of m/z 235 for
      CA(3)P1EC and m/z 249 for CA(4)P1EC. Recoveries of synthesized CA(3)P1EC and
      CA(4)P1EC in various spiked water samples ranged from 82 to 92% with relative
      standard deviations (RSD) lesser than 7%. The limits of quantitation (LOQ) of
      CA(3)P1EC and CA(4)P1EC were estimated to be 0.005 and 0.01 microg/l in 100ml of
      water samples, respectively. The concentrations of CA(4)P1EC residues were
      detected in the aquatic environment ranging from n.d. to 3.24 microg/l. The
      results show that the synthesized CA(4)P1EC has been successfully applied to more
      accurately determine the concentrations of CA(4)P1EC residues in water samples.

PMID- 16806246
TI  - Enantiomeric purity methods for three pharmaceutical compounds by electrokinetic
      capillary chromatography utilizing highly sulfated-gamma-cyclodextrin as the
      chiral selector.
AB  - Methods for enantiomeric purity by electrokinetic chromatography were developed
      and validated for three pharmaceutical compounds, each utilizing highly sulfated
      gamma-cyclodextrin (HS-gamma-CD) as the chiral recognition agent. Two of the
      compounds are weak bases, hence charged at low pH, and the third is a quaternary
      nitrogen compound, charged at all pH. In each instance quantification was via an
      authentic reference standard with addition of an internal standard. Separation
      was on a 61 cm x 50 microm untreated capillary under reverse polarity with a
      background electrolyte of 5% HS-gamma-CD in pH 2.50 lithium phosphate buffer.
      Each method was validated with respect to the usual validation parameters,
      notably recovery and precision, yielding results, including limits of detection
      and quantitation, that allow reporting the minor enantiomer to 0.1% and less. In
      applying the methods, all batches of bulk drug tested were shown to be of
      enantiomeric purity > or =99.9%.

PMID- 16806247
TI  - How does column packing microstructure affect column efficiency in liquid
      chromatography?
AB  - Full three-dimensional computer simulations of the fluid flow and dispersion
      characteristics of model nonporous chromatographic packings are reported.
      Interstitial porosity and packing defects are varied in an attempt to understand
      the chromatographic consequences of the packing microstructure. The tracer zone
      dispersion is calculated in the form of plate height as a function of fluid
      velocity for seven model particle packs where particles are selectively removed
      from the packs in clusters of varying size and topology. In an attempt to examine
      the consequences of loose but random packs, the velocities and zone dispersion of
      seven defect-free packs are simulated over the range 0.36< or =epsilon< or =0.50,
      where epsilon is the interstitial porosity. The results indicate that defect-free
      loose packings can give good chromatographic efficiency but the efficiency can
      vary depending on subtle details of the pack. When the defect population
      increases, the zone dispersion increases accordingly. For a particle pack where
      6% of the particles are removed from an epsilon=0.36 pack, approximately 33% of
      the column efficiency is lost. These results show that it is far more important
      in column packing to prevent defect sites leading to inhomogeneous packing rather
      than obtaining the highest density pack with the smallest interstitial void
      volume.

PMID- 16806248
TI  - On-rod standardization technique for time-weighted average water sampling with a
      polydimethylsiloxane rod.
AB  - In this study, a polydimethylsiloxane (PDMS) rod was developed as a passive
      sampler, based on the solid-phase microextraction (SPME) technique. The on-rod
      standardization technique was applied to the PDMS rod passive sampler. Using the
      desorption of the pre-loaded standard on the PDMS rod to calibrate the absorption
      of the target analytes allows for the determination of the time-weighted average
      (TWA) concentrations of pollutants in the aqueous media. The PDMS rod passive
      sampler with the on-rod standardization technique was tested in the laboratory
      with a flow-through system and was subsequently applied to measure TWA
      concentrations of polycyclic aromatic hydrocarbons (PAHs) in the field (Hamilton
      Harbour, Hamilton, Ont., Canada). Both the laboratory and field experiments
      demonstrated that, with the on-rod standardization technique, the PDMS rod can be
      successfully used as a passive sampler for TWA water sampling in the field. The
      PDMS rod passive sampler benefits from the inherent advantages of the SPME
      approach: it incorporates sampling, isolation and enrichment into one step. The
      design of this system also addressed the additional needs for passive sampling
      techniques, providing an economical approach to field sampling that is also easy
      to deploy. Rather, with this approach, TWA concentrations of target analytes can
      be obtained by one sampler, and can be analyzed directly, with no further sample
      preparation treatment required.

PMID- 16806249
TI  - Micellar electrokinetic capillary chromatography--synchronous monitoring of
      substrate and products in the myrosinase catalysed hydrolysis of glucosinolates.
AB  - A micellar electrokinetic capillary chromatography (MECC) method has been
      developed for monitoring the myrosinase catalysed hydrolysis of 2-hydroxy
      substituted glucosinolates and the simultaneous formation of the corresponding
      degradation products (oxazolidine-2-thiones (OZTs) and nitriles). Glucosibarin
      ((2R)-2-hydroxy-2-phenylethylglucosinolate) was chosen as the model glucosinolate
      owing to the difficulties in determining hydrolysis rates of this type of
      substrates in traditional UV-assays. The method was afterwards validated with
      glucobarbarin ((2S)-2-hydroxy-2-phenylethylglucosinolate) and progoitrin ((2R)-2
      hydroxybut-3-enylglucosinolate). Aromatic glucosinolates without a 2-hydroxy
      group in their side chains, such as glucotropaeolin (benzylglucosinolate) and
      gluconasturtiin (phenethylglucosinolate) were also tested. Formation of the
      glucosinolate hydrolysis products was monitored simultaneously at 206 nm and 230
      nm. This allowed estimation of the extinction coefficient of the OZT derived from
      glucosibarin, which was found to be 18,000 M(-1) cm(-1) and 12,000 M(-1) cm(-1)
      at 206 nm and 230 nm, respectively. The developed method has limit of detection
      of 0.04 mM and 0.06 mM and limit of quantification of 0.2 mM and 0.3 mM for the
      glucosibarin derived OZT and nitrile, respectively. Linearity of the
      glucosinolate concentration was examined at six concentration levels from 2.5 mM
      to 100 mM and at 206 nm a straight line (R(2)=0.9996) was obtained. The number of
      theoretical plates (N) at the optimal system conditions was 245,000 for the
      intact glucosibarin, 264,000 for the OZT and 252,000 for the nitrile.

PMID- 16806250
TI  - Multiple dual-mode centrifugal partition chromatography, a semi-continuous
      development mode for routine laboratory-scale purifications.
AB  - Nowadays, centrifugal partition chromatography (CPC) separations can be routinely
      achieved at the laboratory scale. The solvent system selection has been made
      easy, as generic sets of solvent systems are described in publications and books.
      This approach, however, generally reduces the scope of optimization strategies
      for two important parameters: selectivity and sample solubility. This can be very
      limiting for the preparative separation of structurally similar compounds.
      Multiple dual-mode (MDM) CPC has been developed to provide an easy-to-use
      alternative technique to circumvent this problem. A MDM separation consists of a
      succession of dual-mode runs (i.e. multiple inversion of stationary and mobile
      phase) that can only be achieved because both chromatographic phases are liquids.
      This original elution mode is thus a semi-continuous process with a classical
      sample injection and which only requires a single CPC column. Underlying
      mechanisms of MDM were studied using a model mixture of acenaphthylene and
      naphthalene. A mixture of two synthetic pairs of diastereomers was then
      successfully submitted to MDM CPC, in the framework of the synthesis of
      biologically active compounds.

PMID- 16806251
TI  - High-performance liquid chromatographic separation of dihydropyrimidine racemates
      on polysaccharide-derived chiral stationary phases.
AB  - The chromatographic behavior of a set of racemic dihydropyrimidines (DHPMs) has
      been evaluated on two polysaccharide-derived chiral stationary phases under
      normal phase conditions. One of these is coated, the other chemically
      immobilized. The outstanding solvent compatibility of the immobilized chiral
      stationary phase (CSP) permits the use of solvents such as ethyl acetate (EtOAc)
      that are unsuitable for coated supports, for which traditional 2-propanol:hexanes
      mixtures have been employed. Drastic changes in the chromatographic retention and
      resolution of DHPMs and, in general, in the separation performances have been
      observed for the two systems. From a practical point of view, EtOAc has been
      proven to be a better choice for the separation of this important class of
      compounds. By comparing molecules different in specific positions of their
      scaffolds, hypotheses concerning the role of individual chemical groups on
      retention and selectivity have been done. These effects have been quantified, in
      some cases, in terms of standard Gibbs energy variations. Even if no
      chromatographic measurements have been made under nonlinear conditions, clear
      indications of the potential use of immobilized chiral adsorptive media operated
      with EtOAc:hexanes mixtures for preparative separations of DHPMs have been
      evidenced.

PMID- 16806252
TI  - Determination of five anthraquinones in medicinal plants by capillary zone
      electrophoresis with beta-cyclodextrin addition.
AB  - A simple and rapid method for the simultaneous determination of five
      anthraquinone derivatives including aloe-emodin, emodin, chrysophanol, physcoin
      and rhein in Rheum species and Polygonum cuspidatum was established by capillary
      zone electrophoresis (CZE) using beta-cyclodextrin (CD) as modifier and urea to
      enhance its solubility. The apparent binding constants of these derivatives with
      beta-CD were evaluated. After an optimization study, the best conditions were
      selected using 35 mM phosphate buffer (pH 11.0) containing 20 mM beta-CD and 2 M
      urea, applied voltage 20 kV and detection at 254 nm. Under such conditions, all
      of the five anthraquinones were baseline-separated within a short analysis time
      of 12 min with symmetrical peaks and high theoretical plate numbers (189,000
      314,000). The RSD values of the migration times and peak areas were 0.6-1.1, 1.3
      1.9% (intra-day) and 0.6-1.5, 1.3-2.8% (inter-day, for a 5-day period),
      respectively. The limits of detection for the analytes (S/N = 3) were 0.33-0.62
      microg/ml. The recoveries were ranged from 93.37 to 107.69%. The proposed method
      was successfully applied to the determination of anthraquinones in ethanol
      extracts of two kinds of Rheum plants (R. palmatum and R. hotaoense) and P.
      cuspidatum.

PMID- 16806253
TI  - Determination of the accessible volume and the interaction parameter in the
      adsorption mode of liquid chromatography.
AB  - The main physical parameters in liquid chromatography of oligomers-the accessible
      volume and the adsorption interaction parameter-are discussed. It is shown, that
      in liquid adsorption chromatography (LAC) there is a linear relation between
      elution volume and the distance of two subsequent peaks of a homologous series.
      From the intercept of the regression lines in such a plot the accessible volume
      can be easily determined at any mobile phase in LAC (corresponding to conditions
      of weak or strong adsorption) without any information about the molar mass of the
      peaks. From the slope of this dependence the adsorption interaction parameter of
      a given repeat unit can be obtained. The accurate determination of the accessible
      volume and the adsorption interaction parameter in the LAC regime is presented
      for PEG, PPG and fatty alcohols on various reversed phase columns with different
      pore size in methanol-water or acetone-water mobile phases. The difference
      between the void volume, the dead volume or hold-up volume (from the solvent peak
      position) and the accessible volume (obtained by this procedure) is discussed.

PMID- 16806254
TI  - Chlorination of aromatic compounds in micellar media: regioselectivity.
AB  - Chlorination of phenol and ortho-chlorophenol was studied in micellar media in
      order to observe the effect on regioselectivity. Hydrogen peroxide/hydrochloric
      acid-aqueous system, which is environmentally a safer route was employed for
      chlorination. Selectivity ratio was found to be dependent on the nature and
      concentration of the surfactant. Ortho/para selectivity ratio up to 12 was
      realized for the chlorination of phenol. 2,6-/2,4-dichlorophenol ratio up to 1.01
      was realized for the chlorination of ortho-chlorophenol.

PMID- 16806255
TI  - A non-invasive quantitative assay to measure murine intestinal inflammation using
      the neutrophil marker lactoferrin.
AB  - Intestinal inflammation in mice is most frequently assessed by histology or FACS,
      processes that necessitate sacrificing mice. We developed a lactoferrin ELISA for
      murine feces to quantify intestinal inflammation in mice with enteric infections
      or colitis. Levels of fecal lactoferrin, a protein secreted by activated
      neutrophils, were consistent with neutrophil infiltration as assessed by
      histology, indicating that this fecal lactoferrin ELISA is a good alternative to
      histology. The fecal lactoferrin ELISA provides a non-invasive, quantitative
      assessment of intestinal inflammation, which should facilitate longitudinal
      studies of the development of and/or therapies reducing intestinal inflammation
      in individual mice and reduce the number of mice needed for such studies.

PMID- 16806256
TI  - Cold hardiness in relation to trace metal stress in the freeze-avoiding beetle
      Tenebrio molitor.
AB  - The antifreeze proteins (AFPs) are a family of proteins characterised by their
      ability to inhibit the growth of ice. These proteins have evolved as a protection
      against lethal freezing in freeze avoiding species. Metal stress has been shown
      to reduce the cold hardening in invertebrates, but no study has investigated how
      this type of stress affects the production of AFPs. This study demonstrates that
      exposure to cadmium (Cd), copper (Cu) and zinc (Zn) reduces the normal
      developmental increase in AFP levels in Tenebrio molitor larvae reared under
      summer conditions. Exposure to winter conditions, however stimulated the
      production of AFPs in the metal exposed larvae, and raised the concentrations of
      AFPs to normal winter levels. The reduced level of AFPs in metal-stressed animals
      acclimated to summer conditions seems to arise from alterations in the normal
      gene expression of AFPs. The results indicate that metal exposure may cause
      freeze avoiding insects to become more susceptible to lethal freezing, as they
      enter the winter with lowered levels of AFPs. Such an effect cannot be revealed
      by ordinary toxicological tests, but may nevertheless be of considerable
      ecological importance.

PMID- 16806257
TI  - On the functional significance of juvenile hormone in the accessory sex glands of
      male Heliothis virescens.
AB  - The storage of large quantities of juvenile hormone (JH) in male abdomens is a
      phenomenon known from some species of moths. Juvenile hormone, stored in male
      accessory sex glands (ASG), may be transferred to the female during copulation,
      but the physiological significance of the JH transfer remains unclear. Here,
      using the moth Heliothis virescens as a model, we show that JH transferred from
      male to the promiscuous female promotes JH synthesis and egg development in the
      female. We propose that this explains the functional significance of JH transfer
      in species that exhibit last male sperm precedence, and that this hormone acts as
      a bioactive substance which the first male to mate uses for co-opting and
      regulating the female's gonadotropic mechanisms, thereby ensuring that despite
      last male sperm precedence he will sire a significant number of viable offspring.

PMID- 16806258
TI  - Phylogenetic origins of African and Neotropical Beauveria bassiana s.l. pathogens
      of the coffee berry borer, Hypothenemus hampei.
AB  - A phylogenetic epidemiological study of Beauveria bassiana s.l. was conducted for
      African and Neotropical pathogens of the coffee berry borer (CBB), Hypothenemus
      hampei, based on inferences from two nuclear intergenic regions, EFutr and Bloc.
      CBB pathogens were distributed among four terminal clades, however, the majority
      of African and Neotropical isolates cluster in a well-supported monophyletic
      group, informally designated AFNEO_1. Although the relationship between African
      and Neotropical AFNEO_1 is unresolved, the majority of alleles detected were
      exclusive to either the African or the Neotropical populations. These fixed
      genetic differences suggest that their disjunction predates the world trade in
      coffee. Neotropical AFNEO_1 have a broad host range and CBB pathogens are
      intermixed phylogenetically with isolates from diverse indigenous insects.
      Several Neotropical AFNEO_1 isolates were isolated from coffee plants as
      epiphytes or endophytes, thus plants themselves may potentially serve as
      reservoirs of pathogens against their insect pests. Topological incongruence
      between the EFutr and Bloc phylogenies of Neotropical AFNEO_1 may signify that
      individuals within this population are recombining.

PMID- 16806259
TI  - The effect of myosin regulatory light chain phosphorylation on the frequency
      dependent regulation of cardiac function.
AB  - Although it has been suggested that in cardiac muscle the phosphorylation level
      of myosin regulatory light chain (RLC) correlates with frequency of stimulation,
      its significance in the modulation of the force-frequency and pressure-frequency
      relationships remains unclear. We examined the role of RLC phosphorylation on the
      force-frequency relation (papillary muscles), the pressure-frequency relation
      (Langendorff perfused hearts) and shortening-frequency relation (isolated cardiac
      myocytes) in nontransgenic (NTG) and transgenic mouse hearts expressing a
      nonphosphorylatable RLC protein (RLC(P-)). At 22 degrees C, NTG and RLC(P-)
      muscles showed a negative force-frequency relation. At 32 degrees C, at
      frequencies above 1 Hz, both groups showed a flat force-frequency relation. There
      was a small increase in RLC phosphorylation in NTG muscles when the frequency of
      stimulation was increased from 0.2 Hz to 4.0 Hz. However, the level of RLC
      phosphorylation in these isolated muscles was significantly lower compared to
      samples taken from NTG intact hearts. In perfused hearts, there was no difference
      in the slope of pressure-frequency relationship between groups, but the RLC(P-)
      group consistently developed a reduced systolic pressure and demonstrated a
      decreased contractility. There was no difference in the level of RLC
      phosphorylation in hearts paced at 300 and 600 bpm. In RLC(P-) hearts, the level
      of TnI phosphorylation was reduced compared to NTG. There was no change in the
      expression of PLB between groups, but expression of SERCA2 was increased in
      hearts from RLC(P-) compared to NTG. In isolated cardiac myocytes, there was no
      change in shortening-frequency relationship between groups. Moreover, there was
      no change in Ca(2+) transient parameters in cells from NTG and RLC(P-) hearts.
      Our data demonstrate that in cardiac muscle RLC phosphorylation is not an
      essential determinant of force- and pressure-frequency relations but the absence
      of RLC phosphorylation decreases contractility in force/pressure developing
      preparations.

PMID- 16806260
TI  - An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects
      of angiotensin II and endothelin-1.
AB  - Leptin is a 16 kDa product of the obesity gene secreted primarily by adipocytes.
      We recently identified cardiomyocytes as a target for the direct hypertrophic
      effects of leptin and suggested that leptin may be a biological link between
      obesity and cardiovascular pathologies. Activation of the renin-angiotensin and
      endothelin systems is associated with development of cardiovascular diseases and
      plasma renin levels are elevated in obese individuals. We therefore determined
      possible interaction between these factors in mediating hypertrophy in cultured
      neonatal rat ventricular myocytes. Treatment for 24 h with leptin (3.1 nM),
      angiotensin II (100 nM) or endothelin-1 (ET-1, 10 nM) significantly increased
      cell area by 37%, 36% and 35%, respectively and significantly increased gene
      expression of myosin light chain-2 and alpha-skeletal actin as well as leucine
      incorporation. The hypertrophic effects of all three agents were prevented by
      leptin and a leptin triple mutant receptor antagonist whereas the AT(1) receptor
      blocker (Sar1-lle(8))-Ang II or the ET(A) receptor blocker BQ123 was ineffective
      against leptin-induced hypertrophy. Both angiotensin II and ET-1 significantly
      increased leptin levels in the culture medium by fivefold. Moreover, both
      angiotensin II and ET-1 increased the gene expression of the short form (OBRa) by
      180% and long form (OBRb) of leptin receptors by 200%, and this increase was
      abolished by both leptin receptor and leptin antibodies and leptin triple mutant.
      Although both angiotensin II and ET-1 increased phosphorylation of MAPK (p38,
      ERK1/2 and JNK) and NF-kappaB, the ability of leptin blockade to attenuate the
      hypertrophic responses was generally dissociated from these effects suggesting an
      alternate, yet to be identified cellular pathway mediating this role of leptin.
      Our studies therefore suggest a novel autocrine function for leptin in mediating
      the hypertrophic effects of both angiotensin II and ET-1 in cardiac myocytes.

PMID- 16806261
TI  - PKA-mediated ERK1/2 inactivation and hsp70 gene expression following exercise.
AB  - Exercise induces the expression of the cardioprotective protein, Hsp70, through
      the activation of its transcription factor HSF1. Recently, we reported that
      administration of a protein kinase A (PKA) inhibitor suppressed exercise-induced
      hsp70 gene expression, suggesting a role for PKA in the regulation of HSF1
      activation in vivo. While the mechanism by which PKA regulates HSF1 is unclear,
      studies in vitro have reported that HSF1 is phosphorylated on two serine residues
      by mitogen activated protein kinases (MAPKs); ERK1/2 (ser307) and JNK/SAPK
      (ser363). As PKA is a regulator of these protein kinases, the current study
      examined the role of PKA in their activation and subsequent regulation of
      exercise-induced hsp70 gene expression. Following treadmill-running exercise (60
      min at 30 m/min; 2% grade), both ERK1/2 and JNK/SAPK demonstrated distinct
      phosphorylation profiles. Increased phosphorylation of ERK1/2 was observed
      immediately post-exercise, whereas JNK/SAPK phosphorylation was not significantly
      elevated until 30 min post-exercise. Administration of the PKA inhibitor (H89;
      0.360 mg/kg) maintained ERK1/2 phosphorylation to at least 30 min post exercise
      (n = 5; P < 0.05) while JNK/SAPK phosphorylation was unaltered. Inhibition of
      this PKA-mediated increase in ERK1/2 phosphorylation through the simultaneous
      administration of an ERK1/2 inhibitor (UB-1026; 0.25 mg/kg) restored exercise
      induced hsp70 mRNA levels in PKA-inhibited rats that previously demonstrated a
      suppressed response (P < 0.05). Given that ERK1/2 has been shown to be a negative
      regulator of HSF1 in vitro, these results suggest a role for ERK1/2 in the PKA
      mediated regulation of HSF1 activation following exercise.

PMID- 16806262
TI  - Strain-stimulated hypertrophy in cardiac myocytes is mediated by reactive oxygen
      species-dependent Ras S-glutathiolation.
AB  - Although reactive oxygen species (ROS) appear to play a central role in mediating
      myocardial hypertrophy in response to hemodynamic overload, little is known about
      the molecular targets by which ROS regulate growth signaling. In cardiac
      myocytes, we tested the hypothesis that mechanical strain causes cellular
      hypertrophy via ROS-dependent post-translational modification of Ras leading to
      activation of the Raf/Mek/Erk growth pathway. Cyclic mechanical strain increased
      Ras activity by 1.5 to 1.6-fold. Adenoviral overexpression of the N17 dominant
      negative mutant of Ras inhibited strain-stimulated Erk activation and protein
      synthesis. Strain-stimulated Ras activation was inhibited by overexpression of
      catalase, indicating that it is redox-dependent. Strain caused S-glutathiolation
      of Ras, which was inhibited by catalase overexpression and reversed by DTT. MALDI
      TOF mass spectrometry demonstrated that in myocytes subjected to strain there was
      S-glutathiolation of Ras at Cys118. Adenoviral overexpression of a mutated Ras in
      which Cys118 was substituted with serine inhibited strain-stimulated S
      glutathiolation of Ras, Erk activation and protein synthesis. Overexpression of
      glutaredoxin-1 likewise inhibited strain-stimulated Ras S-glutathiolation, Ras
      activation, Erk activation and protein synthesis. These findings indicate that
      mechanical strain causes ROS-dependent S-glutathiolation of Ras at Cys118,
      leading to myocyte hypertrophy via activation of the Raf/Mek/Erk pathway.

PMID- 16806263
TI  - Attenuation of cardiac dysfunction by a PPAR-alpha agonist is associated with
      down-regulation of redox-regulated transcription factors.
AB  - Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a key regulator
      of lipid and glucose metabolism and is implicated in inflammation. We
      investigated the effects of the PPAR-alpha activator fenofibrate on, as well as
      the role of redox-regulated transcription factors, in the development of left
      ventricular (LV) hypertrophy and heart failure in Dahl salt-sensitive (DS) rats.
      DS rats were fed a high-salt diet and treated with either fenofibrate (30 or 50
      mg/kg per day) or vehicle from 7 weeks of age. Fenofibrate inhibited the
      development of compensated hypertensive LV hypertrophy, attenuated the LV
      relaxation abnormality and systolic dysfunction, and improved the survival rate
      in DS rats. It also prevented a decrease in the ratio of reduced to oxidized
      glutathione and inhibited up-regulation of the DNA binding activities of the
      redox-regulated transcription factors NF-kappaB, AP-1, Egr-1, SP1, and Ets-1
      induced in the left ventricle by the high-salt diet. Expression of target genes
      for these transcription factors, including those for adhesion molecules (VCAM-1,
      ICAM-1), cytokines (MCP-1), growth factors (TGF-beta, PDGF-B), and osteopontin,
      was also increased by the high-salt diet in a manner sensitive to treatment with
      fenofibrate. Furthermore, the infiltration of macrophages and T lymphocytes into
      the left ventricle and the increase in the plasma concentration of C-reactive
      protein were inhibited by fenofibrate. The PPAR-alpha activator fenofibrate thus
      attenuated the progression of heart failure and improved the survival rate in
      this rat model. These effects were associated with inhibition of the inflammatory
      response and of activation of redox-regulated transcription factors in the left
      ventricle.

PMID- 16806264
TI  - Cigarette smoke exposure impairs VEGF-induced endothelial cell migration: role of
      NO and reactive oxygen species.
AB  - Endothelial dysfunction is one of the earliest pathological effects of cigarette
      smoking. Vascular endothelial growth factor (VEGF) has been shown to be an
      important regulator of endothelial healing and growth. Accordingly, we tested the
      hypothesis that cigarette smoke exposure impairs VEGF actions in endothelial
      cells. In human umbilical vein endothelial cells (HUVECs), cigarette smoke
      extracts (CSE) inhibited VEGF-induced tube formation in the matrigel assay. CSE
      did not affect HUVECs proliferation, but significantly reduced cellular migration
      in response to VEGF. This impaired migratory activity was associated with a
      reduced expression of alpha(v)beta(3), alpha(v)beta(5), alpha(5)beta(1) and
      alpha(2)beta(1) integrins. The Akt/eNOS/NO pathway has been shown to be important
      for VEGF-induced endothelial cell migration. We found that CSE inhibited Akt/eNOS
      phosphorylation and NO release in VEGF-stimulated HUVECs. This was associated
      with an increased generation of reactive oxygen species (ROS). Importantly, in
      HUVECs exposed to CSE, treatment with antioxidants (NAC, vitamin C) reduced ROS
      formation and rescued VEGF-induced NO release, cellular migration and tube
      formation. Moreover, treatment with NO donors (SNAP, SNP) or a cGMP analog (8-Br
      cGMP) rescued integrin expression, cellular migration and tube formation in
      endothelial cells exposed to CSE. (1) Cigarette smoke exposure impairs VEGF
      induced endothelial cell migration and tube formation. (2) The mechanism involves
      increased generation of ROS, decreased expression of surface integrins together
      with a blockade of the Akt/eNOS/NO pathway. (3) These findings could contribute
      to explain the negative effect of cigarette smoking on endothelial function and
      vessel growth.

PMID- 16806265
TI  - Noradrenergic neuron-specific overexpression of nNOS in cardiac sympathetic
      nerves decreases neurotransmission.
AB  - Gene transfer of neuronal nitric oxide synthase (nNOS) with nonspecific
      adenoviral vectors can cause promiscuous transduction. We provide direct evidence
      that nNOS targeted only to cardiac sympathetic neurons inhibits sympathetic
      neurotransmission. An adenovirus constructed with a noradrenergic neuron-specific
      promoter (PRSx8), driving nNOS or enhanced green fluorescence protein (eGFP) gene
      expression caused exclusive expression in tyrosine hydroxylase (TH) positive rat
      cardiac sympathetic neurons. There was no detectable leakage of transgene
      expression in other cell types in the preparation nor did the transgene express
      in choline acetyltransferase (CHAT)-positive intracardiac cholinergic ganglia.
      Functionally, Ad.PRS-nNOS gene transfer increased nNOS activity and significantly
      reduced norephinephrine release evoked by field stimulation of isolated right
      atria. These effects were reversed by the NOS inhibitor N(omega)-Nitro-L
      arginine. Our results demonstrate that noradrenergic cell-specific gene transfer
      with nNOS can inhibit cardiac sympathetic neurotransmission. This targeted
      technique may provide a novel method for reducing presynaptic sympathetic
      hyperactivity.

PMID- 16806266
TI  - Characterization of the functional domains of Escherichia coli RNase II.
AB  - RNase II is a single-stranded-specific 3'-exoribonuclease that degrades RNA
      generating 5'-mononucleotides. This enzyme is the prototype of an ubiquitous
      family of enzymes that are crucial in RNA metabolism and share a similar domain
      organization. By sequence prediction, three different domains have been assigned
      to the Escherichia coli RNase II: two RNA-binding domains at each end of the
      protein (CSD and S1), and a central RNB catalytic domain. In this work we have
      performed a functional characterization of these domains in order to address
      their role in the activity of RNase II. We have constructed a large set of RNase
      II truncated proteins and compared them to the wild-type regarding their
      exoribonucleolytic activity and RNA-binding ability. The dissociation constants
      were determined using different single- or double-stranded substrates. The
      results obtained revealed that S1 is the most important domain in the
      establishment of stable RNA-protein complexes, and its elimination results in a
      drastic reduction on RNA-binding ability. In addition, we also demonstrate that
      the N-terminal CSD plays a very specific role in RNase II, preventing a tight
      binding of the enzyme to single-stranded poly(A) chains. Moreover, the
      biochemical results obtained with RNB mutant that lacks both putative RNA-binding
      domains, revealed the presence of an additional region involved in RNA binding.
      Such region, was identified by sequence analysis and secondary structure
      prediction as a third putative RNA-binding domain located at the N-terminal part
      of RNB catalytic domain.

PMID- 16806267
TI  - Crystal structure of the catalytic domain of human MAP kinase phosphatase 5:
      structural insight into constitutively active phosphatase.
AB  - MAP kinase phosphatase 5 (MKP5) is a member of the mitogen-activated protein
      kinase phosphatase (MKP) family and selectively dephosphorylates JNK and p38. We
      have determined the crystal structure of the catalytic domain of human MKP5 (MKP5
      C) to 1.6 A. In previously reported MKP-C structures, the residues that
      constitute the active site are seriously deviated from the active conformation of
      protein tyrosine phosphatases (PTPs), which are accompanied by low catalytic
      activity. High activities of MKPs are achieved by binding their cognate
      substrates, representing substrate-induced activation. However, the MKP5-C
      structure adopts an active conformation of PTP even in the absence of its
      substrate binding, which is consistent with the previous results that MKP5 solely
      possesses the intrinsic activity. Further, we identify a sequence motif common to
      the members of MKPs having low catalytic activity by comparing structures and
      sequences of other MKPs. Our structural information provides an explanation of
      constitutive activity of MKP5 as well as the structural insight into substrate
      induced activation occurred in other MKPs.

PMID- 16806268
TI  - Structural basis for detoxification and oxidative stress protection in membranes.
AB  - Synthesis of mediators of fever, pain and inflammation as well as protection
      against reactive molecules and oxidative stress is a hallmark of the MAPEG
      superfamily (membrane associated proteins in eicosanoid and glutathione
      metabolism). The structure of a MAPEG member, rat microsomal glutathione
      transferase 1, at 3.2 A resolution, solved here in complex with glutathione by
      electron crystallography, defines the active site location and a cytosolic domain
      involved in enzyme activation. The glutathione binding site is found to be
      different from that of the canonical soluble glutathione transferases. The
      architecture of the homotrimer supports a catalytic mechanism involving subunit
      interactions and reveals both cytosolic and membraneous substrate entry sites,
      providing a rationale for the membrane location of the enzyme.

PMID- 16806269
TI  - Visual hallucinations in Parkinson's disease: clues to separate origins.
AB  - Our paper discusses two experimental studies suggesting that Visual
      Hallucinations (VH) in Parkinson's Disease (PD) may have separate origins. The
      first is a prospective 8years study evaluating the appearance of VH, visual
      abnormalities assessed by Visual Evoked Potentials (VEPs) and REM sleep Behaviour
      Disorder (RBD), in 80 PD patients treated with l-Dopa and Dopaminoagonists (DA).
      In chronically treated, cognitively unimpaired, PD patients VH were statistically
      related (p=0.001) to RBD occurrence and high DA doses. Visual abnormalities were
      significantly reduced by l-Dopa or DA intake, and were statistically unrelated to
      VH. The second study involved PD patients placed in a Virtual Reality
      Environment, to decontextualize visual input. When motor symptoms worsened and
      VEP abnormalities developed patients consistently described hallucinatory
      dysperceptions of the virtual environment. The two studies therefore show that VH
      can occur in two seemingly distinct conditions, one is related to chronic
      treatment and to a sleep disorder frequently observed in PD, the other is
      probably related to a hypodopaminergic state. Our studies support a recently
      proposed integrative model of VH, and show that the neural circuits purported to
      explain VH must include the retinal dopaminergic system and the REM sleep
      regulatory system.

PMID- 16806270
TI  - The "posture second" strategy: a review of wrong priorities in Parkinson's
      disease.
AB  - Falls are common in Parkinson's disease. It remains difficult to predict these
      falls, presumably because clinical balance tests assess single components of
      postural control, whereas everyday fall mechanisms are typically more
      complicated. A substantial proportion of everyday falls appears to occur while
      Parkinson patients attempt to perform multiple tasks at the same time.
      Furthermore, little attention is generally paid to the possible contribution of
      cognitive impairments to falls. The importance of mental dysfunction is supported
      by the fact that cognitive loading while walking or balancing can lead to marked
      deteriorations in postural performance, and there is some evidence to suggest
      that such "dual tasking" is particularly difficult for elderly persons with
      dementia or depression. We examined what strategies Parkinson patients used when
      a basic walking task became increasingly challenging by adding additional tasks
      (both motor and cognitive). Most patients could perform a simple "dual task"
      test: simultaneously walking and answering simple questions. However, as the
      walking task became more complex, patients' performance began to deteriorate.
      Interestingly, this was reflected not only by failure to answer questions, but
      also by an increasing number of blocks in motor performance (walking and
      balancing). This behaviour was different from that of both young and elderly
      controls, who appeared to sacrifice performance on the cognitive task in order to
      optimise their gait and balance ("posture first" strategy). Preliminary evidence
      suggest that impaired multiple task performance is associated with a two-fold
      increased risk of sustaining falls in daily life. We conclude that Parkinson
      patients are less inclined than healthy persons to maintain a safe gait. Instead,
      Parkinson patients use a "posture second" strategy and treat all elements of a
      complex task with equal priority, which in daily life may go at the expense of
      maintaining balance and lead to falls.

PMID- 16806271
TI  - Non-dopaminergic treatment of cognitive impairment and dementia in Parkinson's
      disease: a review.
AB  - OBJECTIVE: To review the clinical management of cognitive impairment and dementia
      related to Parkinson's disease (PD), with emphasis on pharmacologic intervention
      strategies such as cholinesterase inhibitors. DATA SOURCES: A MEDLINE, EMBASE,
      PsychINFO, and Cochrane Collaboration search of English language literature from
      1970 to 2004 was performed to identify reviews, studies, case reports, and
      letters pertaining to the treatment of cognitive impairment in PD. The
      bibliographies of selected articles were reviewed for additional references.
      STUDY SELECTION: Human studies or case reports in adults with PD describing the
      use of drug and other therapies for the treatment of cognitive impairment in PD.
      DATA EXTRACTION: Studies were reviewed for study design, number of subjects,
      outcome measures, dosage, side-effects, particularly, worsening of PD motor
      symptoms. CONCLUSION: The strongest evidence for the pharmacological treatment of
      cognitive impairment and dementia in PD supports the use of cholinesterase
      inhibitors. Evidence for the efficacy and safety of other agents in PD dementia
      is either insufficient or inconclusive, but offers intriguing clues for potential
      future treatments. No reports from the Cochrane Collaboration were found.

PMID- 16806272
TI  - Novel neuroprotection by caffeine and adenosine A(2A) receptor antagonists in
      animal models of Parkinson's disease.
AB  - The adenosine A(2A) receptor has recently emerged as a leading non-dopaminergic
      therapeutic target for Parkinson's disease, largely due to the restricted
      distribution of the receptor in the striatum and the profound interaction between
      adenosine and dopamine receptors in brain. Two lines of research in particular
      have demonstrated the promise of the A(2A) receptor antagonists as novel anti
      parkinsonian drugs. First, building on extensive preclinical animal studies, the
      A(2A) receptor antagonist KW6002 has demonstrated its potential to increase motor
      activity in PD patients of the advanced stage in a recent clinical phase IIB
      trial. Second, recently two prospective epidemiological studies of large cohorts
      have firmly established the inverse relationship between the consumption of
      caffeine (a non-specific adenosine antagonist) and the risk of developing PD. The
      potential neuroprotective effect of caffeine and A(2A) receptor antagonists in PD
      is further substantiated by the demonstration that pharmacological blockade (by
      caffeine or specific A(2A) antagonists) or genetic depletion of the A(2A)
      receptor attenuated dopaminergic neurotoxicity and neurodegeneration in animal
      models of PD. Moreover, A(2A) receptor antagonism-mediated neuroprotection goes
      beyond PD models and can be extended to a variety of other brain injuries induced
      by stroke, excitotoxicity and mitochondrial toxins. Intensive investigations are
      under way to dissect out common cellular mechanisms (such as A(2A) receptor
      modulation of neuroinflammation) which may underlie the broad spectrum of
      neuroprotection by A(2A) receptor inactivation in brain.

PMID- 16806273
TI  - Region with persistent high frequency of multiple sclerosis in Croatia and
      Slovenia.
AB  - OBJECTIVE: The aim of this study was to evaluate the prevalence of multiple
      sclerosis (MS), and to determine the clinical characteristics and the occurrence
      of familial MS in the Gorski kotar-Kocevje region, which was previously
      considered to be a region of high prevalence of MS. METHODS: All clinically and
      laboratory supported definite cases of MS according to Poser's criteria, living
      residents of the chosen area on June 1, 1999 were included in the study. The
      patients were ascertained through national case registers for MS at the
      University Medical Centers (Rijeka and Ljubljana), registries of the national
      associations of MS patients, as well as from the medical records of regional
      outpatient clinics. RESULTS: The crude annual prevalence per 100,000 population
      was 151.9 (95% CI 123.2-187.4). 28.7% of patients had a history of MS among first
      , second-, or third-degree relatives. The frequency of primary progressive course
      of disease was 23.5%. The sex ratio (F/M) was 1.41. CONCLUSION: A stable high
      prevalence of MS as well as a high number of familial MS cases was identified in
      the neighbouring regions of Slovenia and Croatia.

PMID- 16806274
TI  - Involuntary defection and the evolutionary origins of empathy.
AB  - An occasional involuntary defection (IVD)--being unable, rather than unwilling,
      to donate help to others--is an intrinsic attribute of reciprocal cooperation
      (2003. J. Theor. Biol. 225-285). In fact, it is easy to see that--barring special
      circumstances--individuals that can donate help whenever requested do not need
      help of the same kind from others. That is, it is by no means clear why such
      individuals should participate in symmetric reciprocity interactions. In this
      paper, I analyse the consequences of introducing IVD into direct reciprocity
      modeling and show that a simple form of empathy--not retaliating after being
      punished for IVD--is a prerequisite for evolutionarily stable cooperation.
      Furthermore: we will see that the stability of this, empathic retaliator,
      strategy increases with the number of opportunities for cooperative exchanges in
      the life of an average individual.

PMID- 16806275
TI  - Motor potential profile and a robust method for extracting it from time series of
      motor positions.
AB  - Molecular motors are small, and, as a result, motor operation is dominated by
      high-viscous friction and large thermal fluctuations from the surrounding fluid
      environment. The small size has hindered, in many ways, the studies of physical
      mechanisms of molecular motors. For a macroscopic motor, it is possible to
      observe/record experimentally the internal operation details of the motor. This
      is not yet possible for molecular motors. The chemical reaction in a molecular
      motor has many occupancy states, each having a different effect on the motor
      motion. The overall effect of the chemical reaction on the motor motion can be
      characterized by the motor potential profile. The potential profile reveals how
      the motor force changes with position in a motor step, which may lead to insights
      into how the chemical reaction is coupled to force generation. In this article,
      we propose a mathematical formulation and a robust method for constructing motor
      potential profiles from time series of motor positions measured in single
      molecule experiments. Numerical examples based on simulated data are shown to
      demonstrate the method. Interestingly, it is the small size of molecular motors
      (negligible inertia) that makes it possible to recover the potential profile from
      time series of motor positions. For a macroscopic motor, the variation of driving
      force within a cycle is smoothed out by the large inertia.

PMID- 16806276
TI  - Dynamics, stability and inheritance of somatic DNA methylation imprints.
AB  - Recent research highlights the role of CpG methylation in genomic imprinting,
      histone and chromatin modification, transcriptional regulation, and 'gene
      silencing' in cancer development. An unresolved issue, however, is the role of
      stable inheritance of factors that manage epigenetic imprints in renewing or
      expanding cell populations in soma. Here we propose a mathematical model of CpG
      methylation that is consistent with the cooperative roles of de novo and
      maintenance methylation. This model describes (1) the evolution of methylation
      imprints toward stable, yet noisy equilibria, (2) bifurcations in methylation
      levels, thus the dual stability of both hypo- and hypermethylated genomic
      regions, and (3) sporadic transitions from hypo- to hypermethylated equilibria as
      a result of methylation noise in a finite system of CpG sites. Our model not only
      affords an explanation of the persistent coexistence of these two equilibria, but
      also of sporadic changes of site-specific methylation levels that may alter
      preset epigenetic imprints in a renewing cell population.

PMID- 16806277
TI  - Using stacked generalization to predict membrane protein types based on pseudo
      amino acid composition.
AB  - Membrane proteins are vitally important for many biological processes and have
      become an attractive target for both basic research and drug design. Knowledge of
      membrane protein types often provides useful clues in deducing the functions of
      uncharacterized membrane proteins. With the unprecedented increasing of newly
      found protein sequences in the post-genomic era, it is highly demanded to develop
      an automated method for fast and accurately identifying the types of membrane
      proteins according to their amino acid sequences. Although quite a few
      identifiers have been developed in this regard through various approaches, such
      as covariant discriminant (CD), support vector machine (SVM), artificial neural
      network (ANN), and K-nearest neighbor (KNN), classifier the way they operate the
      identification is basically individual. As is well known, wise persons usually
      take into account the opinions from several experts rather than rely on only one
      when they are making critical decisions. Likewise, a sophisticated identifier
      should be trained by several different modes. In view of this, based on the frame
      of pseudo-amino acid that can incorporate a considerable amount of sequence-order
      effects, a novel approach called "stacked generalization" or "stacking" has been
      introduced. Unlike the "bagging" and "boosting" approaches which only combine the
      classifiers of a same type, the stacking approach can combine several different
      types of classifiers through a meta-classifier to maximize the generalization
      accuracy. The results thus obtained were very encouraging. It is anticipated that
      the stacking approach may also hold a high potential to improve the
      identification quality for, among many other protein attributes, subcellular
      location, enzyme family class, protease type, and protein-protein interaction
      type. The stacked generalization classifier is available as a web-server named
      "SG-MPt_Pred" at: http://202.120.37.186/bioinf/wangsq/service.htm.

PMID- 16806278
TI  - Colorimetric heparinase assay for alternative anti-metastatic activity.
AB  - Heparanase has been previously associated with the metastatic potential,
      inflammation, and angiogenesis of tumor cells. Heparanase activity has been
      detected by means of UV absorption, radiolabeled substrates, electrophoretic
      migration, and heparan sulfate affinity assays. However, those methods have
      proven to be somewhat problematic with regards to application to actual
      biological samples, the accessibility of the immobilized substrates, experimental
      sensitivity, and the separation of degraded products. Rather than focusing on
      heparanase activity, then, we have developed a rapid, alternative colorimetric
      heparinase assay, on the basis of the recent finding that sulfated disaccharides
      generated from heparin by bacterial heparinase exhibit biological properties
      comparable to those from heparan sulfate by mammalian heparanase. In this study,
      the concentrations of porcine heparin and bacterial heparinase I were determined
      using a Sigma Diagnostics Kit. Morus alba was selected as a candidate through
      this assay system, and an inhibitor, resveratrol, was purified from its methanol
      extract. Its anti-metastatic effects on the pulmonary metastasis of murine B16
      melanoma cells were also evaluated. Our findings suggest that this assay may
      prove useful as a diagnostic tool for heparinase inhibition, as an alternative
      anti-metastatic target.

PMID- 16806279
TI  - Altered renal sodium handling in spontaneously hypertensive rats (SHR) after
      hypertonic saline intracerebroventricular injection: role of renal nerves.
AB  - The mechanism by which blood pressure rises in the SHR strain remains to be
      elucidated. Also, there is a surprising lack of experimental data on the
      natriuretic mechanisms induced by intracerebroventricular (ICV) injection of
      hyperosmotic saline (HoS) in SHR. In normotensive animals ICV injection of HoS
      causes coordinated responses including natriuresis and inhibition of renal
      sympathetic nerve activity. In the present study, we hypothesized that presumable
      blunting of the sympathoinhibitory response to centrally injected HoS may
      contribute to a lack of suppression of efferent renal nerve outflow in SHR. To
      test this hypothesis, the present study evaluates the influence of renal
      denervation after central HoS injection at increasing concentration on urinary
      sodium handling in SHR compared with age-matched normotensive WKy rats. The study
      confirmed previous data showing pronounced natriuretic response to centrally HoS
      stimuli but also demonstrated that the creatinine clearance (C(Cr)) and
      fractional sodium excretion responses diminished as graded NaCl concentrations
      were increased in WKy rats but not in SHR. In SHR, increased FE(Na) obtained by
      central administration of 0.90 M NaCl was produced by increases in proximal
      (FEP(Na)) and post-proximal fractional urinary sodium rejection without changes
      in C(Cr), indicating a direct tubular effect. Renal denervation caused
      significant antinatriuresis by decreased C(Cr) and increased FEP(Na) reabsorption
      in WKy but not in SHR. This study suggests that natriuresis observed only after
      higher centrally HoS stimuli with a rightward shift of dose-response curve
      provides evidence of a down-regulation of target organ responsiveness of
      periventricular areas of genetic hypertensive rats.

PMID- 16806280
TI  - MMP-9 antisense oligodeoxynucleotide exerts an inhibitory effect on osteoclastic
      bone resorption by suppressing cell migration.
AB  - We have previously shown that matrix metalloproteinases (MMPs) play a role in
      osteoclastic bone resorption by facilitating migration of osteoclastic cells
      toward bone surface through matrices. Of MMPs identified so far, MMP-9 is likely
      the most important proteinase for the action, since osteoclasts express this
      enzyme at a tremendously high level. However, no direct evidence has been
      provided to demonstrate its contribution to bone resorption. In this study, to
      address this point, we used an MMP-9 antisense phosphothiorate
      oligodeoxynucleotide (S-ODN), which was shown to inhibit the protein synthesis of
      MMP-9 efficiently. We demonstrated that the antisense S-ODN inhibited
      osteoclastic pit formation on matrigel-coated dentine slices in a concentration
      dependent manner with a maximum reduction of total pit volume by 53% at 10
      microM. These results, taken together, suggest that MMP-9 is involved in
      osteoclastic bone resorption process possibly by facilitating migration of
      osteoclasts through proteoglican-rich matrices.

PMID- 16806281
TI  - Antioxidant effect of tetrahydrocurcumin in streptozotocin-nicotinamide induced
      diabetic rats.
AB  - Oxidative stress has been suggested to be a contributory factor in development
      and complication of diabetes. In the present study, we have investigated the
      effect of tetrahydrocurcumin (THC), one of the active metabolites of curcumin on
      antioxidants status in streptozotocin-nicotinamide induced diabetic rats. Oral
      administration of THC at 80 mg/kg body weight of diabetic rats for 45 days
      resulted in significant reduction in blood glucose and significant increase in
      plasma insulin levels. In addition, THC caused significant increase in the
      activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione
      S-transferase, reduced glutathione, vitamin C and vitamin E in liver and kidney
      of diabetic rats with significant decrease in thiobarbituric acid reactive
      substances (TBARS) and hydroperoxides formation in liver and kidney, suggesting
      its role in protection against lipid peroxidation induced membrane damage. These
      biochemical observations were supplemented by histopathological examination of
      liver and kidney section. The antidiabetic and antioxidant effects of THC are
      more potent than those of curcumin at the same dose. Results of the present study
      indicated that THC showed antioxidant effect in addition to its antidiabetic
      effect in type 2 diabetic rats.

PMID- 16806282
TI  - Chemical pollution--has it been tackled sufficiently? Visions of a healthier
      Baltic Sea.

PMID- 16806283
TI  - Are toxic contaminants accumulating in Massachusetts coastal sediments following
      startup of the Massachusetts Bay outfall: a comprehensive comparison of baseline
      and post-diversion periods.
AB  - The Massachusetts Water Resources Authority (MWRA) conducts monitoring to address
      concerns related to the 2000 diversion of secondarily treated effluent discharge
      into Massachusetts Bay. Baseline data (1992-2000) showed multiple regions defined
      by physical and chemical composition. Near the Massachusetts Bay outfall, there
      is a series of heterogeneous sediments in relatively close proximity to the
      primary historic source of contaminants (Boston Harbor). Farfield sediments
      exhibited greater compositional definition from one another, which was attributed
      to the greater spatial separation of the sampling locations. Factors that
      influence contaminant variability include local and distributed sources, and are
      primarily related to gradients in depositional environments. Post-diversion
      sediment data suggest that 4 years of treated effluent discharge has not
      increased contaminant concentrations to the bay system. However, abundance of the
      sewage tracer, Clostridium perfringens, has increased variably in sediments
      located within 2 km of the outfall, providing a distinct effluent signal near the
      outfall.

PMID- 16806284
TI  - Spatial distribution of nine metals in surface sediment of an urban estuary prior
      to a large scale reclamation project.

PMID- 16806285
TI  - Polycyclic aromatic hydrocarbons (PAHs) in small island coastal environments: a
      case study from harbours in Guam, Micronesia.

PMID- 16806286
TI  - Trace metal contamination and benthic assemblages in Subae estuarine system,
      Brazil.

PMID- 16806287
TI  - Conceptual, methodological and computational issues concerning the compartmental
      modeling of a complex biological system: Postprandial inter-organ metabolism of
      dietary nitrogen in humans.
AB  - A multi-compartmental model has been developed to describe dietary nitrogen (N)
      postprandial distribution and metabolism in humans. This paper details the entire
      process of model development, including the successive steps of its construction,
      parameter estimation and validation. The model was built using experimental data
      on dietary N kinetics in certain accessible pools of the intestine, blood and
      urine in healthy adults fed a [15N]-labeled protein meal. A 13-compartment, 21
      parameter model was selected from candidate models of increasing order as being
      the minimum structure able to properly fit experimental data for all sampled
      compartments. Problems of theoretical identifiability and numerical
      identification of the model both constituted mathematical challenges that were
      difficult to solve because of the large number of unknown parameters and the few
      experimental data available. For this reason, new robust and reliable methods
      were applied, which enabled (i) a check that all model parameters could
      theoretically uniquely be determined and (ii) an estimation of their numerical
      values with satisfactory precision from the experimental data. Finally, model
      validation was completed by first verifying its a posteriori identifiability and
      then carrying out external validation.

PMID- 16806288
TI  - Lymphangiogenesis in the developing lung promoted by VEGF-A.
AB  - Understanding the basic processes of late-stage pulmonary vascular development is
      essential as this period corresponds to the stage when preterm infants have
      increased chance of survival. During this period, refinement of the gas exchange
      unit leads to close apposition of the capillary vasculature and airway epithelium
      through thinning of the mesenchyme, formation of alveolar septae and functional
      adaptation of endothelial cells into vessels including pulmonary lymphatics. The
      pulmonary lymphatic network promotes efficient gas exchange through maintaining
      interstitial fluid balance. Through conditional transgene regulation, we found
      that a modest, pathologically relevant increase in vascular endothelial growth
      factor A (VEGF-A) in distal lung during only the perinatal period adversely
      affected final refinement of the gas exchange unit. VEGF-A induction disrupted
      the established vascular network, increased endothelial cell number, altered
      endothelial ultrastructure and reduced mesenchymal thinning. In addition, VEGF-A
      induction caused a 3-fold increase in small vessels identified as lymphatics in
      distal lung. mRNA levels of lymphangiogenic factors VEGF-D/-C were unchanged,
      while levels of the cognate receptor VEGFR-3 increased. The responses to VEGF-A
      induction in the perinatal period differ from those during early lung development
      when endothelial migration, but not proliferation altered initial vascular
      patterning (Akeson, A.L., Greenberg, J.M., Cameron, J.E., Thompson, F.Y., Brooks,
      S.K., Wiginton, D., Whitsett, J.A., 2003. Temporal and spatial regulation of VEGF
      A controls vascular patterning in the embryonic lung. Dev. Biol. 264, 443-455).
      The late-stage response resembles that of adult lung to VEGF-inducing stimuli
      including injury and disease. These data suggest that VEGF-A influences the
      balance between development of blood and lymphatic vasculature during lung
      organogenesis.

PMID- 16806289
TI  - Three-dimensional visualization of microvessel architecture of whole-mount tissue
      by confocal microscopy.
AB  - The three-dimensional architecture of the nascent microvascular network is a
      critical determinant of vascular perfusion in the setting of regenerative growth,
      vasculopathies and cancer. Current methods for microvessel visualization are
      limited by insufficient penetration and instability of endothelial immunolabels,
      inadequate vascular perfusion by the high-viscosity polymers used for vascular
      casting, and destruction of tissue stroma during the processing required for
      scanning electron microscopy. The aim of this study was to develop whole-mount
      tissue processing methods for 3D in situ visualization of the microvasculature
      that were also compatible with supplementary labeling for other structures of
      interest in the tissue microenvironment. Here, we present techniques that allow
      imaging of the microvasculature by confocal microscopy, to depths of up to 1500
      mum below the specimen surface. Our approach includes labeling luminal surfaces
      of endothelial cells by i.v. injection of fluorescently conjugated lectin and
      filling the microvasculature with carbon or fluorescent nanoparticles/Mercox,
      followed by optical clearing of thick tissue sections to reduce light scatter and
      permit 3D visualization of microvessel morphology deep into the sample. Notably,
      tissue stroma is preserved, allowing simultaneous labeling of other structures by
      immunohistochemistry or nuclear dyes. Results are presented for various murine
      tissues including fat, muscle, heart and brain under conditions of normal health,
      as well as in the setting of a glioma model growing in the subcutaneous space or
      orthotopically in the brain parenchyma.

PMID- 16806290
TI  - Multi-image particle tracking velocimetry of the microcirculation using
      fluorescent nanoparticles.
AB  - Particle tracking velocimetry provides a Lagrangian description of flow
      properties in the microcirculation. To determine the utility of fluorescent
      nanoparticles to provide Lagrangian coordinates, we tracked these particles both
      in vitro and in vivo. The particles had a neutral charge and fluorescence
      intensity greater than 1,000 times the PKH26-labeled red blood cells. At image
      acquisition rates of 60 frames per second, particles were tracked at velocities
      up to 4,000 microm/s. Morphometric changes reflecting streaking artifact were
      significant at velocities of 4,000 microm/s (P < 0.05), but not at lower
      velocities (P > 0.05). Intravital microscopy monitoring after intravenous
      injection of the particles demonstrated a circulation half-life that was
      inversely related to particle size: 500 nm nanoparticles demonstrated a smaller
      change in plasma concentration than larger particles. Regardless of the size of
      the particles, more than 50% of the recovered fluorescence was located in the
      liver. These results suggest that fluorescent nanoparticles provide a convenient
      and practical Lagrangian description of flow velocity in the microcirculation.

PMID- 16806291
TI  - Biomarkers and molecular epidemiology--present state and future trends:
      concluding remarks.

PMID- 16806292
TI  - Comparative genetic mutation frequencies based on amino acid composition
      differences.
AB  - Genetic variation inferred from large-scale amino acid composition comparisons
      among genomes and chromosomes of several species, Saccharomyces cerevisiae,
      Drosophila melanogaster, Ceanorhabditis elegans, H. sapiens, is shown to be
      correlated (highest, r(2)=0.9855, p<0.01) with reported mutation rates for
      various genes in these species. This study, based largely on pseudogene data,
      helps to establish reference mutation frequencies that are likely to be
      representative of overall genome mutation rates in each of the species examined,
      and provides further insight into heterogeneity of mutation rates among genomes.

PMID- 16806293
TI  - Genetic polymorphisms and haplotype structures of the CYP4A22 gene in a Japanese
      population.
AB  - The CYP4A fatty acid monooxygenases oxidize endogenous arachidonic acid to 20
      hydroxyeicosatetraenoic acid that acts as a regulator of blood pressure. Among
      the isoforms of the CYP4A subfamily, the human CYP4A22 was recently identified.
      In this study, we report the comprehensive investigation of polymorphisms in the
      CYP4A22 gene. To investigate genetic variation in CYP4A22 in 191 Japanese
      subjects, we used denaturing HPLC (DHPLC) and direct sequencing. Our
      investigation has enabled the identification of 13 sequence variations in the
      CYP4A22 coding region, thereby demonstrating for the first time that this gene is
      subject to polymorphism. Two of these sequence variations correspond to silent
      mutations located in exons 8 (His323His) and 9 (Gly390Gly). Nine of these
      sequence variations correspond to missense mutations located in exons 1
      (Arg11Cys), 3 (Arg126Trp), 4 (Gly130Ser and Asn152Tyr), 5 (Val185Phe), 6
      (Cys231Arg), 7 (Lys276Thr), 10 (Leu428Pro), and 12 (Leu509Phe). One of these
      sequence variations corresponds to nonsense mutations located in exon 9
      (Gln368stop). The 13th mutation corresponds to a nucleotide deletion (G7067del)
      that causes a frameshift and consequently results in a stop codon 80 nucleotides
      downstream. In addition to the wild-type CYP4A22*1 allele, 20 variants, namely
      CYP4A22*2-15, were characterized by haplotype analysis. Based on these data, we
      concluded that allelic variants of the human CYP4A22 gene exist and speculated
      that some of these variants may be functionally relevant.

PMID- 16806294
TI  - Genomic instability of human aberrant crypt foci measured by inter-(simple
      sequence repeat) PCR and array-CGH.
AB  - Aberrant crypt foci (ACF) are the earliest identifiable neoplastic lesions in the
      colon. Thirty-two ACFs were examined for genomic instability in forms detectable
      either by inter-(simple sequence repeat) PCR or by array comparative genomic
      hybridization [array-CGH]. One-fourth of ACFs revealed moderate instability by
      inter-(simple sequence repeat) PCR; none showed amplifications or deletions on
      array-CGH. The absence of genomic events detectible by BAC array-CGH indicates
      early events in colorectal tumor progression are typically smaller than the
      approximate 150 kb size of a BAC clone insert.

PMID- 16806295
TI  - Chronic DHEAS administration facilitates hippocampal long-term potentiation via
      an amplification of Src-dependent NMDA receptor signaling.
AB  - Dehydroepiandrosterone sulfate (DHEAS) has well characterized effects on memory
      and cognitive performances. Recently we have reported that repetitive
      administration of DHEAS lowers the threshold pulse number in inducing activity
      dependent long-term potentiation (LTP) in rat hippocampal Schaffer collateral-CA1
      synapses, in which a sub-threshold high frequency stimulation (HFS, 30 pulses at
      100 Hz) for normal rats could induce robust LTP in DHEAS-treated rats (Chen et
      al., 2006). Here we report that the sub-threshold HFS could trigger the
      phosphorylation of Src and ERK2 in the DHEAS-treated rats, but not in control
      rats. We found in slices obtained from the DHEAS-treated rats that NMDA-induced
      intracellular Ca2+([Ca2+]i) transients in CA1 pyramidal neurons were
      significantly potentiated, which was essential for the Src and ERK2
      phosphorylations. The activation of ERK2, a downstream factor of Src family
      kinase, was required for the DHEAS-facilitated LTP. The Src family kinase
      inhibitor PP2, but not its inactive homologue PP3, attenuated the NMDA-induced
      [Ca2+]i increase and abolished the DHEAS-facilitated LTP. These findings suggest
      that the chronic administration of DHEAS brings the NMDA receptor (NMDAr) to a
      potentiated state that causes an enough level of [Ca2+]i increase for LTP
      induction even by the sub-threshold HFS. The potentiated [Ca2+]i transient by the
      sub-threshold HFS may trigger the Src phosphorylation that will further
      potentiate NMDAr followed by an activation of ERK2 and LTP induction. This novel
      postsynaptic NMDAr/Src-mediated signal amplification through "NMDAr-Ca2+-->Src-
      >NMDAr-Ca2+" cycle may play a pivotal role in the DHEAS-facilitated LTP
      induction.

PMID- 16806296
TI  - Isolation and pharmacological characterisation of hostoxin-1, a postsynaptic
      neurotoxin from the venom of the Stephen's banded snake (Hoplocephalus
      stephensi).
AB  - Envenoming by the Stephen's banded snake (Hoplocephalus stephensi) is not usually
      characterised by neurotoxicity. The present study describes the pharmacological
      characterisation of hostoxin-1 (MW 6660 Da), the first neurotoxin to be isolated
      from the venom of the Stephen's banded snake. Hostoxin-1 (0.3-1.0 microM) caused
      concentration-dependent inhibition of indirect twitches of the chick biventer
      cervicis nerve-muscle preparation. The neurotoxic activity of hostoxin-1 (0.3
      microM) was irreversible by washing, but significantly reversed by the addition
      of CSL tiger snake antivenom (5 units/ml) added at t90 (i.e. time at which
      twitches were inhibited by 90%). In addition, hostoxin-1 (0.3 microM) inhibited
      responses to exogenous acetylcholine and carbachol, but not KCl, indicating a
      postsynaptic mode of action. Hostoxin-1 (5-30 nM) displayed pseudo-irreversible
      antagonism at the skeletal muscle nicotinic receptor with a pA2 value of 8.45+/
      0.32 (i.e. approximately 100-fold more potent than tubocurarine). H. stephensi
      venom displayed a high level of PLA2 activity (specific activity 100.1+/-4.4
      micromol/min/mg). However, the activity of hostoxin-1 was negligible. Partial N
      terminal sequencing of hostoxin-1 indicates that it has high sequence homology
      with other elapid short-chain neurotoxins.

PMID- 16806297
TI  - Treatment with valproate after status epilepticus: effect on neuronal damage,
      epileptogenesis, and behavioral alterations in rats.
AB  - Epileptogenesis, i.e. the process leading to epilepsy with spontaneous recurrent
      seizures, can be initiated by a number of brain damaging insults, including
      traumatic brain injury, status epilepticus (SE), and stroke. Such acquired
      epilepsy is often associated with memory impairment and behavioral problems.
      There has been a growing interest in the use of antiepileptic drugs (AEDs) for
      neuroprotection and prevention or modification of epileptogenesis induced by such
      brain insults. One promising candidate in this respect is valproic acid (VPA), a
      widely used AED that has been reported to exert neuroprotective activity in a
      number of in vitro and in vivo models. The present study investigated whether VPA
      reduces brain damage and improves functional outcome in a rat model of post-SE
      epilepsy. A self-sustaining SE was induced by prolonged electrical stimulation of
      the basal amygdala via a depth electrode. SE was terminated after 4 h by
      diazepam, immediately followed by onset of treatment with VPA. VPA was injected
      i.p. at a bolus dose of 400 mg/kg, followed by three times daily administration
      of 200 mg/kg for 4 weeks. A control group received vehicle instead of VPA after
      SE. Spontaneous seizures were recorded in all rats of both groups following
      termination of treatment, without significant inter-group difference in seizure
      frequency or severity. However, treatment with VPA after SE prevented the
      hyperexcitability and locomotor hyperactivity observed in vehicle-treated
      epileptic rats. Furthermore, VPA completely counteracted the neuronal damage in
      the hippocampal formation, including the dentate hilus. The data demonstrate
      that, although VPA does not prevent the occurrence of spontaneous seizures after
      SE, it exerts powerful neuroprotective effects and prevents part of the
      behavioral alterations, demonstrating that administration of VPA immediately
      after SE exerts a favorable effect on long-term functional outcome.

PMID- 16806298
TI  - Context-dependent regulation of embryonic stem cell differentiation by mGlu4
      metabotropic glutamate receptors.
AB  - The mGlu5 receptor is the only metabotropic glutamate receptor subtype expressed
      by mouse embryonic stem (ES) cells grown under non-differentiating conditions
      [Cappuccio, I., Spinanti, P. Porcellini, A., Desiderati, F., De Vita, T., Storto,
      M., Capobianco, L., Battaglia, G., Nicoletti, F., Melchiorri, D., 2005.
      Endogenous activation of mGlu5 metabotropic glutamate receptors supports self
      renewal of cultured mouse embryonic stem cells. Neuropharmacology 1, 196-205]. We
      now report that ES cells differentiating into embryoid bodies (EBs) progressively
      lose mGlu5 receptors and begin to express mGlu4 receptors at both mRNA and
      proteinc level. A 4-day treatment of EBs with the mGlu4 receptor agonist, L-2
      amino-4-phosphonobutanoate (L-AP4), increased mRNA levels of the mesoderm marker,
      brachyury and the endoderm marker, H19, and decreased the expression of the
      transcript for the primitive ectoderm marker, fibroblast-growth factor-5 (FGF-5).
      These effects were prevented by the mGlu4 receptor antagonists, alpha
      methylserine-O-phosphate (MSOP). Plating of EBs for 4 days in vitro in ITSFn
      medium induced cell differentiation towards a neural lineage, as reflected by the
      expression of the intermediate filament protein, nestin, and the homeobox
      protein, Dlx-2. Pharmacological activation of mGlu4 receptors during cell
      incubation in ITSFn medium increased the expression of both neural markers.
      Similar results were obtained when neural differentiation was induced by exposure
      of EBs to retinoic acid. These data suggest that differentiation of cultured ES
      cells is associated with changes in the expression pattern of mGlu receptors and
      that activation of mGlu4 receptors affects cell differentiation in a context
      dependent manner.

PMID- 16806299
TI  - A role for vanilloid receptor 1 (TRPV1) and endocannabinnoid signalling in the
      regulation of spontaneous and L-DOPA induced locomotion in normal and reserpine
      treated rats.
AB  - Although most commonly associated with actions at cannabinoid CB1 receptors on
      the extracellular surface of the plasma membrane, the endocannabinoid anandamide
      (AEA) is also transported into the cell, by the putative anandamide membrane
      transporter (AMT), and activates the vanilloid receptor 1 (TRPV1) at an
      intracellular site. AEA is then inactivated by fatty acid amide hydrolase (FAAH).
      As systemic administration of TRPV1 ligands reduces locomotor activity in normal
      rodents, we hypothesised that activation of TRPV1 by endocannabinoids could play
      a role in the control of voluntary movement and that such actions could be
      regulated by AMT and FAAH. Motor activity was assessed in normal, in reserpine
      treated, and in reserpine-treated rats treated with L-DOPA. In normal rats, the
      TRPV1 agonist capsaicin (1 mg/kg) or the FAAH inhibitor URB597 (10 mg/kg) caused
      a significant reduction in movement in both the horizontal (locomotion) and
      vertical (rearing) planes (-45% and -53% respectively with capsaicin; -33% and 
      37% for URB597). Capsaicin-induced hypolocomotion was attenuated by the TRPV1
      antagonist, capsazepine. There was no effect of capsaicin, URB597 or the AMT
      inhibitor OMDM-2 on motor activity in reserpine-treated rats. L-DOPA treatment of
      reserpine-treated rats elicited high levels of motor activity in both the
      horizontal and vertical planes. Horizontal activity was attenuated by capsaicin
      (1 mg/kg, -60%), but not by URB597 (10 mg/kg) or OMDM-2 (5 mg/kg). Vertical
      activity was attenuated by capsaicin (1 mg/kg, -61%) and by URB597 (10 mg/kg, 
      54%), but not by OMDM-2. These data suggest that activation of the TRPV1 system
      can suppress spontaneous locomotion in normal animals and modulates several L
      DOPA-induced behaviours in reserpine-treated rats.

PMID- 16806300
TI  - Antinociceptive activity of chemical congeners of improgan: optimization of side
      chain length leads to the discovery of a new, potent, non-opioid analgesic.
AB  - Improgan is a chemical congener of the H2 antagonist cimetidine which shows the
      profile of a highly effective analgesic when administered directly into the CNS.
      Although the improgan receptor is unknown, improgan activates analgesic pathways
      which are independent of opioids, but may utilize cannabinoid mechanisms. To
      discover selective, potent, improgan-like drugs, seven compounds chemically
      related to improgan were synthesized and tested for antinociceptive activity in
      rats after intracerebroventricular (icv) administration. Among a series of
      improgan congeners in which the alkyl chain length of improgan ((-CH2)3-) was
      varied, five compounds showed full agonist antinociceptive activity with
      potencies greater than that of improgan. VUF5420 (containing (-CH2)4-, EC50 =
      86.1 nmol) produced maximal antinociceptive activity after doses which showed no
      motor impairment or other obvious toxicity, and was 2.3-fold more potent than
      improgan (EC50 = 199.5 nmol). As found previously with improgan, VUF5420-induced
      antinociception was unaffected by administration of the opioid antagonist
      naltrexone, but was inhibited by the CB1 antagonist SR141716A, suggesting a non
      opioid, cannabinoid-related analgesic action. However, VUF5420 showed very low
      affinity (Kd approximately 10 microM) on CB1-receptor activation of 35S-GTPgammaS
      binding, indicating that this drug does not directly interact with the CB1
      receptor in vivo. The present results show that VUF5420 is a high potency,
      improgan-like, non-opioid analgesic which may indirectly activate cannabinoid
      pain-relieving mechanisms.

PMID- 16806301
TI  - 4-aminopyridine, a Kv channel antagonist, prevents apoptosis of rat cerebellar
      granule neurons.
AB  - Compelling evidence indicates that excessive potassium (K+) efflux and
      intracellular K+ depletion are the key early steps in apoptosis. Previously, we
      reported that apoptosis of cerebellar granule neurons induced by incubation in
      low-K+ (5 mM) and serum-free medium was associated with an increase in A-type
      transient inactivation of K+ channel current (IA) amplitude and modulation of
      channels' gating properties. Here, we showed that a classic K+ channel blocker, 4
      aminopyradine (4-AP), significantly inhibited IA amplitude in a concentration
      dependent manner (reduction of current by 10 microM and 10 mM 4-AP was 11.4+/
      1.3% and 72.2+/-3.3%, respectively). Moreover, 4-AP modified the steady-state
      activation and inactivation kinetics of IA channels, such that the activation and
      inactivation curves were shifted to the right about 20 mV and 17 mV,
      respectively. Fluorescence staining showed that 4-AP dramatically increased the
      viability of cells undergoing apoptosis in a dose-dependent manner. That is,
      while 5 mM 4-AP was present, cell viability was 84.9+/-5.2%. Consistent with the
      cell viability analysis, internucleosomal DNA fragmentation by gel
      electrophoresis analysis showed that 5 mM 4-AP also protected against neuronal
      apoptosis. Furthermore, 4-AP significantly inhibited cytochrome c release and
      caspase-3 activity induced by low-K+/serum-free incubation. Finally, current
      clamp analysis indicated that 5 mM 4-AP did not significantly depolarize the
      membrane potential. These results suggest that 4-AP has robust neuroprotective
      effects on apoptotic granule cells. The neuroprotective effect of 4-AP is likely
      not due to membrane depolarization, but rather that 4-AP may modulate the gating
      properties of IA channels in an anti-apoptotic manner.

PMID- 16806302
TI  - Null mutation of the alpha4 nicotinic receptor subunit increases the propensity
      of muscarinic-mediated neuronal bursting in mouse hippocampal slices.
AB  - Alpha4 subunit nicotinic cholinergic receptor (nAChR) knock out mice (KO) have a
      greater susceptibility to proconvulsant-induced seizures than do wild type (WT).
      The underlying mechanisms remain obscure. We tested whether such seizure-like
      activity was reflected in bursting activity of hippocampal neurons by recording
      with intracellular microelectrodes from CA1 pyramidal neurons in slices from WT
      and KO mice. Intriguingly, while carbachol-induced bursting activity occurred in
      only 21% of WT slices, qualitatively identical patterns of bursting occurred in
      72% of KO slices. Extracellular recordings from CA1 and CA3 regions suggest that
      carbachol-mediated population activity was regionalized in our preparations. The
      relative weighting of excitatory to inhibitory synaptic potentials was similar
      between WT and alpha4 KO mice. However, burst-firing cells had a smaller input
      time constant than non-bursters. Low-concentration DHbetaE (selective alpha4beta2
      nAChR antagonist) did not increase the propensity of WT slices to burst-fire,
      indicating that absence of alpha4 subunits per se, cannot explain the differences
      in activity between slices from WT and KO mice. These observations suggest that
      alpha4 nAChRs are unlikely to be involved in modulating the pattern of bursting
      neural activity, but their absence could induce subtle developmental changes in
      the sensitivity of hippocampal circuits to develop this behaviour.

PMID- 16806303
TI  - HU0622: a small molecule promoting GAP-43 activation and neurotrophic effects.
AB  - During the course of neuronal development or regeneration, the axonal growth cone
      protein growth-associated protein 43 (GAP-43) is expressed in a great majority of
      differentiating neurons, suggesting that the regulation of this gene is tied to
      important differentiation signals common to many neurons. In order to discover
      non-peptide molecules capable of mimicking the effects of NGF, we developed a
      reporter gene assay system based on measurement of light production in PC12 cells
      stably transfected with the luciferase reporter gene, the expression of which
      depends on the transcriptional activation of GAP-43. High throughput screening of
      the proprietary compound collection using this system revealed (E,E)-1-[5-(3,4
      dihydroxyphenyl)-1-oxo-2,4-pentadienyl]piperidine (HU0622), a piperine
      derivative, to be an activator of GAP-43 transcription. HU0622 strongly induced
      neurite outgrowth and extension in PC12 and sensory neuronal cultures of chick
      dorsal root ganglia. The compound induced sustained extracellular signal
      regulated kinase (ERK) activation that is crucial for neurite outgrowth activity
      without activating NGF receptor, TrkA. Furthermore, HU0622 as well as NGF
      promoted PC12 survival under serum-free conditions and activated Akt/protein
      kinase B downstream from phosphatidylinositol 3-kinase (PI3K). HU0622 also
      promoted survival of rat dorsal root ganglion neurons deprived of NGF. HU0622, a
      small non-peptidyl molecule, may be a novel promising lead compound for the
      stimulation of nerve regeneration.

PMID- 16806304
TI  - Ethanol inhibition of NMDA-induced responses and acute tolerance to the
      inhibition in rat rostral ventrolateral medulla in vivo: Involvement of cAMP
      dependent protein kinases.
AB  - Our recent study showed that intravenous ethanol selectively inhibited the
      pressor effects elicited by the microinjection of N-methyl-D-aspartate (NMDA)
      into rostral ventrolateral medulla (RVLM) and acute tolerance to the inhibition
      was observed during prolonged application of ethanol in anesthetized Sprague
      Dawley rats. In this study, we examined the role of the cAMP-dependent protein
      kinase (PKA) signaling pathway in acute tolerance to ethanol inhibition of NMDA
      induced responses in rat RVLM. A significant increase in the level of PKA
      regulated phosphoserine 897 on the NMDA NR1 subunit was found in the
      rostroventral medulla during acute ethanol tolerance. Reduction of NMDA-induced
      pressor effects was observed at 10 min but disappeared at 40 min after continuous
      ethanol infusion. This effect was dose-dependently blocked by microinjection of
      KT5720 (0.04-4 pmol, a selective PKA inhibitor) or cAMPS-Rp (0.02, 0.2 pmol, a
      cAMP antagonist) into the RVLM 10 min post-injection of ethanol; KT 5720 or cAMPS
      Rp alone at doses tested had no significant effects on NMDA-induced responses.
      Post-treatment with cAMPS-Sp (10 pmol, a cAMP activator) did not affect acute
      ethanol tolerance. Interestingly, administration of KT 5720 (0.4, 4 pmol) or
      cAMPS-Rp (2,10 pmol) into the RVLM 20 min before the injection of ethanol also
      reduced the inhibitory effects of ethanol on NMDA-induced pressor effects in a
      dose-dependent manner. Our results provide the first in vivo evidence that PKA
      signaling pathways participate in acute tolerance to ethanol inhibition of NMDA
      receptor function. Furthermore, PKA-mediated signaling pathways may also be
      involved in the interaction between ethanol and NMDA receptors.

PMID- 16806305
TI  - Enhanced antinociceptive effects of morphine in histamine H2 receptor gene
      knockout mice.
AB  - We have previously shown that antinociceptive effects of morphine are enhanced in
      histamine H1 receptor gene knockout mice. In the present study, involvement of
      supraspinal histamine H2 receptor in antinociception by morphine was examined
      using histamine H2 receptor gene knockout (H2KO) mice and histamine H2 receptor
      antagonists. Antinociception was evaluated by assays for thermal (hot-plate, tail
      flick and paw-withdrawal tests), mechanical (tail-pressure test) and chemical
      (formalin and capsaicin tests) stimuli. Thresholds for pain perception in H2KO
      mice were higher than wild-type mice. Antinociceptive effects of
      intracerebroventricularly administered morphine were enhanced in the H2KO mice
      compared to wild-type mice. Intracerebroventricular co-administration of morphine
      and cimetidine produced significant antinociceptive effects in the wild-type mice
      when compared to morphine or cimetidine alone. Furthermore, zolantidine, a
      selective and hydrophobic H2 receptor antagonist, enhanced the effects of
      morphine in all nociceptive assays examined. These results suggest that histamine
      exerts inhibitory effects on morphine-induced antinociception through H2
      receptors at the supraspinal level. Our present and previous studies suggest that
      H1 and H2 receptors cooperatively function to modulate pain perception in the
      central nervous system.

PMID- 16806306
TI  - The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function
      in the central nervous system.
AB  - Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti
      inflammatory, and analgesic properties, and it has been shown to interact with
      gamma-aminobutyric acid (GABA) type A receptors (GABAARs) and strychnine
      sensitive glycine receptors in the rat central nervous system. In contrast to a
      proposed agonistic action at these two types of inhibitory receptors,
      pharmacological evidence has shown that, under certain conditions, TCC manifests
      convulsant activity in animals and humans. We now show that the phasic and tonic
      GABAAR-mediated currents recorded from Purkinje cells and granule neurons,
      respectively, in parasagittal cerebellar slices from adult male rats were
      inhibited by TCC in a concentration-dependent manner. The median inhibitory
      concentrations of TCC for these effects were approximately 0.15 and approximately
      0.9 microM, respectively. TCC did not potentiate GABABR-mediated currents in
      hippocampal slices, suggesting that its muscle relaxant action is not mediated by
      GABABRs. Intraperitoneal injection of TCC in rats either alone or in combination
      with negative modulators of GABAergic transmission revealed convulsant and
      proconvulsant actions of this drug. Our data, consistent with clinical
      observations of the epileptogenic effect of this compound, suggest that TCC is a
      potent competitive antagonist of GABAAR function.

PMID- 16806307
TI  - Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition
      of neurotransmitter release in rat nucleus accumbens core.
AB  - We examined the occurrence of functional interactions between CB1 cannabinoid and
      mu opioid receptors in the core of rat nucleus accumbens (NAc core). To that end,
      receptor-mediated inhibition of depolarization (4-aminopyridine)-induced
      [3H]glutamate release and glutamate (NMDA) receptor-stimulated [14C]acetylcholine
      (ACh) and [3H]GABA release was studied in superfused NAc core slices. The
      inhibitory effects of the mu receptor agonist morphine and the CB1 receptor
      agonist HU210 on the release of these neurotransmitters were selectively
      antagonized by the mu receptor antagonist naloxone and the CB1 receptor
      antagonist SR141716A, respectively. Surprisingly, naloxone prevented the
      antagonistic action of SR141716A at CB1 receptors and SR141716A abolished that of
      naloxone at mu receptors mediating inhibition of [3H]glutamate and [3H]GABA
      release. Therefore, these antagonists seem to allosterically interact, indicating
      the involvement of physically associated mu opioid and CB1 cannabinoid receptors.
      Such an interaction between antagonists was not observed at the receptors
      mediating inhibition of [14C]ACh release. Moreover, dose-response curves of the
      agonists showed that mu and CB1 receptors mediating inhibition of [3H]glutamate
      release display a non-additive interaction, whereas these receptors
      synergistically interact regarding their inhibitory control of [3H]GABA release.
      Finally, the apparent allosteric interaction between antagonists was also
      observed regarding the effects of other receptor-selective agonists and
      antagonists at mu opioid and CB1 cannabinoid receptors (mediating inhibition of
      NMDA-induced [3H]GABA release) and must therefore be a unique property of the
      receptors involved. These data suggest the existence of physically associated mu
      opioid and CB1 cannabinoid receptors, whereby activation of these receptors
      results in either a non-additive (glutamate release) or a synergistic (GABA
      release) effect. It is proposed that these allosterically interacting mu and CB1
      receptors in the NAc core may represent G-protein coupled heterodimeric receptor
      complexes.

PMID- 16806308
TI  - The H current blocker ZD7288 decreases epileptiform hyperexcitability in the rat
      neocortex by depressing synaptic transmission.
AB  - Neurons respond to intracellular injection of hyperpolarizing current pulses by
      generating depolarizing sags contributed by a cation current termed Ih. Ih
      modulates neuron excitability and rhythmicity. It is, however, unclear whether
      the net effect of changing Ih leads to facilitation or depression of cortical
      epileptiform activity. Here, we addressed this issue by using field and
      intracellular recordings to study the effects of ZD7288 (10-100 microM), a
      bradycardic agent known to abolish Ih, on the epileptiform discharges (duration =
      2.5 +/- 0.3 s, mean +/- SEM; interval of occurrence = 34.2 +/- 3.3 s, n = 30
      slices) induced in rat neocortical slices by 4-aminopyridine and GABA receptor
      antagonists. ZD7288 abolished the depolarizing sags seen during injection of
      intracellular hyperpolarizing current pulses while increasing resting membrane
      potential and apparent input resistance. These effects, which were fully
      established with 10 microM ZD7288, were associated with a dose-dependent decrease
      in the occurrence of spontaneous epileptiform events and a reduction in their
      duration (the latter change occurring at doses > 20 microM). ZD7288 also caused a
      dose-dependent decrease of background postsynaptic potentials. Finally, ZD7288
      could depress epileptiform activity during Cs+ pre-treatment, a procedure known
      to block Ih. These data indicate that ZD7288 hampers neocortical epileptiform
      synchronization, but also suggest that most of this action reflects the ability
      of ZD7288 to decrease synaptic transmission.

PMID- 16806309
TI  - Mechanism of beta-bungarotoxin in facilitating spontaneous transmitter release at
      neuromuscular synapse.
AB  - The mechanism of the action of beta-bungarotoxin (beta-BuTx) in the facilitation
      of spontaneous transmitter release at neuromuscular synapse was investigated in
      Xenopus cell culture using whole-cell patch clamp recording. Exposure of the
      culture to beta-BuTx dose-dependently enhances the frequency of spontaneous
      synaptic currents (SSCs). Buffering the rise of intracellular Ca2+ with BAPTA-AM
      hampered the facilitation of SSC frequency induced by beta-BuTx. The beta-BuTx
      enhanced SSC frequency was reduced when the pharmacological Ca2+ -ATPase
      inhibitor thapsigargin was used to deplete intracellular Ca2+ store. Application
      of membrane-permeable inhibitors of inositol 1,4,5-trisphosphate (IP3) but not
      ryanodine receptors effectively occluded the increase of SSC frequency elicited
      by beta-BuTx. Treating cells with either wortmannin or LY294002, two structurally
      different inhibitors of phosphatidylinositol 3-kinase (PI3K) and with
      phospholipase C (PLC) inhibitor U73122, abolished the beta-BuTx-induced
      facilitation of synaptic transmission. The beta-BuTx-induced synaptic
      facilitation was completely abolished while there was presynaptic loading of the
      motoneuron with GDPbetaS, a non-hydrolyzable GDP analogue and inhibitor of G
      protein. Taken collectively, these results suggest that beta-BuTx elicits Ca2+
      release from the IP3 sensitive intracellular Ca2+ stores of the presynaptic nerve
      terminal. This is done via PI3K/PLC signaling cascades and G protein activation,
      leading to an enhancement of spontaneous transmitter release.

PMID- 16806310
TI  - The role of configural information in facial emotion recognition in
      schizophrenia.
AB  - The schizophrenia deficit in facial emotion recognition could be accounted for by
      a deficit in processing the configural information of the face. The present
      experiment was designed to further test this hypothesis by studying the face
      inversion effect in a facial emotion recognition task. The ability of 26
      schizophrenic patients and 26 control participants to recognize facial emotions
      on upright and upside-down faces was assessed. Participants were told to state
      whether faces expressed one of six possible emotions (happiness, anger, disgust,
      fear, sadness, neutrality) in two sessions, one with upright faces and the other
      with upside-down faces. Discriminability and the decision criterion were
      computed. The results indicated that the schizophrenic patients were impaired in
      upright facial emotion discrimination by comparison with the controls. They also
      exhibited an inversion effect similar to the controls. However, whereas controls
      tended to adopt a more conservative criterion for all emotions and a liberal
      criterion for neutrality when the faces were upside-down, schizophrenic patients
      presented a decision criterion pattern that was similar for the two orientations
      and similar to controls in upside-down emotion recognition. The lack of a
      decision criterion shift was associated with positive symptoms such as delusions,
      hallucinations, and bizarre behavior. Moreover, positive and negative symptoms
      were associated with inversion effect on discriminability; the more severe the
      symptoms, the weaker the inversion effect. We conclude that individuals with
      schizophrenia do process the configural information of the face. However, further
      investigations are needed to assert whether this information is of good quality
      in schizophrenia.

PMID- 16806311
TI  - The special involvement of the rostrolateral prefrontal cortex in planning
      abilities: an event-related fMRI study with the Tower of London paradigm.
AB  - Planning abilities are essential for the successful management of everyday life
      activities. Although several neuroimaging studies provide evidence that the
      prefrontal cortex is crucially involved in planning, the differential roles of
      its subregions are still a matter of debate. The aim of this study was to
      investigate the neural correlates of planning by focusing on the functional
      differentiation between the dorsolateral and rostrolateral prefrontal cortex
      using the Tower of London (ToL) task and a parametric event-related functional
      MRI design. In order to control for activations unspecific to planning, two
      control conditions were presented, which were matched for the length of single
      events in the ToL task. Seventeen right-handed healthy subjects participated in
      this study. All statistics were reported with corrections for multiple
      comparisons (p < 0.05). Compared to control conditions, activations in the ToL
      task were observed in the dorsolateral prefrontal cortex bilaterally, the right
      ventrolateral and left rostrolateral prefrontal cortex along with the thalamus,
      as well as in the parietal and premotor cortex bilaterally. Task complexity
      dependent analyses revealed that only the left rostrolateral prefrontal cortex
      showed a BOLD signal increase over the four planning levels, which could not be
      observed in the control conditions. Hence, current findings suggest that planning
      involves an extensive fronto-parieto-thalamic network. Within this network, the
      rostrolateral prefrontal cortex seems to be the only region that is exclusively
      reactive to planning specific processes, which we described in terms of
      simultaneous monitoring of internally generated and externally presented
      information.

PMID- 16806312
TI  - Differential activation of the amygdala and the 'social brain' during fearful
      face-processing in Asperger Syndrome.
AB  - Impaired social cognition is a core feature of autism. There is much evidence
      showing people with autism use a different cognitive style than controls for face
      processing. We tested if people with autism would show differential activation of
      social brain areas during a face-processing task. Thirteen adults with high
      functioning autism or Asperger Syndrome (HFA/AS) and 13 matched controls. We used
      fMRI to investigate 'social brain' activity during perception of fearful faces.
      We employed stimuli known to reliably activate the amygdala and other social
      brain areas, and ROI analyses to investigate brain areas responding to facial
      threat as well as those showing a linear response to varying threat intensities.
      We predicted: (1) the HFA/AS group would show differential activation (as opposed
      to merely deficits) of the social brain compared to controls and (2) that social
      brain areas would respond to varied intensity of fear in the control group, but
      not the HFA/AS group. Both predictions were confirmed. The controls showed
      greater activation in the left amygdala and left orbito-frontal cortex, while the
      HFA/AS group showed greater activation in the anterior cingulate gyrus and
      superior temporal cortex. The control group also showed varying responses in
      social brain areas to varying intensities of fearful expression, including
      differential activations in the left and right amygdala. This response in the
      social brain was absent in the HFA/AS group. HFA/AS are associated with different
      patterns of activation of social brain areas during fearful emotion processing,
      and the absence in the HFA/AS brain of a response to varying emotional intensity.

PMID- 16806313
TI  - Patients with Parkinson's disease learn to control complex systems-an indication
      for intact implicit cognitive skill learning.
AB  - Implicit memory and learning mechanisms are composed of multiple processes and
      systems. Previous studies demonstrated a basal ganglia involvement in purely
      cognitive tasks that form stimulus response habits by reinforcement learning such
      as implicit classification learning. We will test the basal ganglia influence on
      two cognitive implicit tasks previously described by Berry and Broadbent, the
      sugar production task and the personal interaction task. Furthermore, we will
      investigate the relationship between certain aspects of an executive dysfunction
      and implicit learning. To this end, we have tested 22 Parkinsonian patients and
      22 age-matched controls on two implicit cognitive tasks, in which participants
      learned to control a complex system. They interacted with the system by choosing
      an input value and obtaining an output that was related in a complex manner to
      the input. The objective was to reach and maintain a specific target value across
      trials (dynamic system learning). The two tasks followed the same underlying
      complex rule but had different surface appearances. Subsequently, participants
      performed an executive test battery including the Stroop test, verbal fluency and
      the Wisconsin card sorting test (WCST). The results demonstrate intact implicit
      learning in patients, despite an executive dysfunction in the Parkinsonian group.
      They lead to the conclusion that the basal ganglia system affected in Parkinson's
      disease does not contribute to the implicit acquisition of a new cognitive skill.
      Furthermore, the Parkinsonian patients were able to reach a specific goal in an
      implicit learning context despite impaired goal directed behaviour in the WCST, a
      classic test of executive functions. These results demonstrate a functional
      independence of implicit cognitive skill learning and certain aspects of
      executive functions.

PMID- 16806315
TI  - Quantifying deficits in the perception of fear and anger in morphed facial
      expressions after bilateral amygdala damage.
AB  - Amygdala damage has been associated with impairments in perceiving facial
      expressions of fear. However, deficits in perceiving other emotions, such as
      anger, and deficits in perceiving emotion blends have not been definitively
      established. One possibility is that methods used to index expression perception
      are susceptible to heuristic use, which may obscure impairments. To examine this,
      we adapted a task used to examine categorical perception of morphed facial
      expressions [Etcoff, N. L., & Magee, J. J. (1992). Categorical perception of
      facial expressions. Cognition, 44(3), 227-240]. In one version of the task,
      expressions were categorized with unlimited time constraints. In the other,
      expressions were presented with limited exposure durations to tap more automatic
      aspects of processing. Three morph progressions were employed: neutral to anger,
      neutral to fear, and fear to anger. Both tasks were administered to a participant
      with bilateral amygdala damage (S.P.), age- and education-matched controls, and
      young controls. The second task was also administered to unilateral temporal
      lobectomy patients. In the first version, S.P. showed impairments relative to
      normal controls on the neutral-to-anger and fear-to-anger morphs, but not on the
      neutral-to-fear morph. However, reaction times suggested that speed-accuracy
      tradeoffs could account for results. In the second version, S.P. showed
      impairments on all morph types relative to all other subject groups. A third
      experiment showed that this deficit did not extend to the perception of morphed
      identities. These results imply that when heuristics use is discouraged on tasks
      utilizing subtle emotion transitions, deficits in the perception of anger and
      anger/fear blends, as well as fear, are evident with bilateral amygdala damage.

PMID- 16806314
TI  - The functional neuroanatomy of autobiographical memory: a meta-analysis.
AB  - Autobiographical memory (AM) entails a complex set of operations, including
      episodic memory, self-reflection, emotion, visual imagery, attention, executive
      functions, and semantic processes. The heterogeneous nature of AM poses
      significant challenges in capturing its behavioral and neuroanatomical
      correlates. Investigators have recently turned their attention to the functional
      neuroanatomy of AM. We used the effect-location method of meta-analysis to
      analyze data from 24 functional imaging studies of AM. The results indicated a
      core neural network of left-lateralized regions, including the medial and
      ventrolateral prefrontal, medial and lateral temporal and retrosplenial/posterior
      cingulate cortices, the temporoparietal junction and the cerebellum. Secondary
      and tertiary regions, less frequently reported in imaging studies of AM, are also
      identified. We examined the neural correlates of putative component processes in
      AM, including, executive functions, self-reflection, episodic remembering and
      visuospatial processing. We also separately analyzed the effect of select
      variables on the AM network across individual studies, including memory age,
      qualitative factors (personal significance, level of detail and vividness),
      semantic and emotional content, and the effect of reference conditions. We found
      that memory age effects on medial temporal lobe structures may be modulated by
      qualitative aspects of memory. Studies using rest as a control task masked
      process-specific components of the AM neural network. Our findings support a
      neural distinction between episodic and semantic memory in AM. Finally, emotional
      events produced a shift in lateralization of the AM network with activation
      observed in emotion-centered regions and deactivation (or lack of activation)
      observed in regions associated with cognitive processes.

PMID- 16806316
TI  - Brain correlates of discourse processing: an fMRI investigation of irony and
      conventional metaphor comprehension.
AB  - Higher levels of discourse processing evoke patterns of cognition and brain
      activation that extend beyond the literal comprehension of sentences. We used
      fMRI to examine brain activation patterns while 16 healthy participants read
      brief three-sentence stories that concluded with either a literal, metaphoric, or
      ironic sentence. The fMRI images acquired during the reading of the critical
      sentence revealed a selective response of the brain to the two types of
      nonliteral utterances. Metaphoric utterances resulted in significantly higher
      levels of activation in the left inferior frontal gyrus and in bilateral inferior
      temporal cortex than the literal and ironic utterances. Ironic statements
      resulted in significantly higher activation levels than literal statements in the
      right superior and middle temporal gyri, with metaphoric statements resulting in
      intermediate levels in these regions. The findings show differential hemispheric
      sensitivity to these aspects of figurative language, and are relevant to models
      of the functional cortical architecture of language processing in connected
      discourse.

PMID- 16806317
TI  - Repetition suppression and semantic enhancement: an investigation of the neural
      correlates of priming.
AB  - The priming of a stimulus by another has become an important tool for exploring
      the neural underpinnings of conceptual representations. However, priming effects
      can derive from many different types of relationships and it is important to
      distinguish between them in order to be able to develop theoretical accounts of
      the representation of conceptual knowledge. While it is well known that
      repetition priming (the repeated presentation of the same stimulus) is associated
      with a reduced neural response, called repetition suppression (RS), the neural
      correlates of semantic priming (when two stimuli are related in meaning but not
      identical) are not so well established. We compared the neural correlates of
      repetition and semantic priming using written words, independently manipulating
      form and meaning. In an fMRI study, subjects saw single words and made a concrete
      abstract decision. Two consecutive words were identical (town-town) or varied
      along a continuum of semantic relatedness, from highly related (cord-string) to
      unrelated (face-sail). We found distinct patterns of activation for repetition
      and semantic priming. Repetition priming was associated with RS in LIFG,
      bilateral parahippocampal gyrus and R fusiform gyrus. We also observed increased
      activation for word repetition in the RMFG and RMTG/STG, which may reflect
      recognition of item's earlier presentation. There was no evidence of suppression
      for semantic relatedness. Semantic priming was associated with enhanced
      activation in multiple bilateral fronto-temporal areas, i.e. semantic
      enhancement. The results suggest that repetition and semantic priming in visual
      word recognition depend on distinct cognitive processes and neural substrates.

PMID- 16806318
TI  - Restricted ocular exploration does not seem to explain simultanagnosia.
AB  - One major function of parietal cortex is to direct our attention towards salient
      stimuli. The present data suggest that it also plays an important role in visual
      gestalt perception. Patients with simultanagnosia following lesions in this area
      are not able to extract the meaning of a visual scene whereas being perfectly
      able to recognise individual objects of this scene. We tested two patients with
      simultanagnosia with hierarchical Navon figures combined with eye movements
      recordings. The patients' performance allowed us to compare directly the scan
      paths in trials in which the global letter shape was recognised with trials in
      which the global letter shape was not recognised. We did not find any obvious
      differences in the eye movement pattern related to the two perceptual situations.
      The two patients did not show a significant problem in shifting their eyes (and
      thus possibly also their attentional focus) to all aspects of the complex visual
      stimulus when attempting to bind together the different elements of spatially
      distributed information. The results demonstrate that restricted ocular
      exploration cannot be the reason for the patients' inability to recognise the
      global shape of stimuli. Our data rather suggest a role of parietal cortex in
      visual gestalt perception that is beyond its role of directing attention towards
      relevant objects.

PMID- 16806319
TI  - Galanin in the PVN increases nutrient intake and changes peripheral hormone
      levels in the rat.
AB  - In self-selection feeding paradigms, rats display differential patterns of
      nutrient (protein, carbohydrate or fat) intake. Factors known to influence this
      selection include brain peptides as well as circadian parameters. In this series
      of experiments we investigated the role of PVN galanin in nutrient intake during
      the early and late dark periods in the rat. Rats were allowed to select between
      three isocaloric diets enriched in protein, carbohydrate or fat. Following a 2
      week adaptation period, the animals' 24-h intake was monitored for 4 weeks.
      Galanin was injected into the PVN and food intake was measured 1, 2 and 24 h post
      injection. Galanin significantly increased the 1 h total food intake but it
      failed to increase the intake of any particular nutrient. Galanin had no effect 2
      or 24 h post-injection. Analysis of the data grouped by preference based on the
      rats 24 h baseline selection patterns over the 4-week period revealed that
      galanin seem to increase the preferred nutrient. That is, galanin preferentially
      increased the intake of the carbohydrate- or fat-rich diet in animals with high
      (over 40% of the total food intake) 24-h baselines in this particular nutrient.
      Finally, analysis of the plasma hormone levels after paraventricular galanin
      administration revealed a significant increase in noradrenaline levels, a small
      reduction in plasma insulin with no effects on adrenaline, glucose or
      corticosterone. The data revealed that galanin in the PVN influences both food
      intake and metabolic functioning. PVN galanin significantly increases sympathetic
      outflow and seems to stimulate the intake of the individual rat's preferred
      macronutrient.

PMID- 16806320
TI  - Chemesthesis from volatile organic compounds: Psychophysical and neural
      responses.
AB  - In Experiment 1, subjects sought to localize the nostril stimulated, left or
      right, in tests with nine esters (acetates, propionates, and butyrates) at
      concentrations meant to trigger chemesthesis (pungency, irritation). The task
      produced psychometric functions for chemesthetic detection unconfounded by
      olfactory sensations. The functions indicated a sharp transition from no
      detection to perfect detection, rather uniform across the esters, which
      themselves varied in potency by two log units. The correlation between the
      thresholds for the eight materials that yielded thresholds and predictions from a
      published linear free energy relationship (LFER) equaled 0.99. In Experiment 2,
      amplitude of the negative mucosal potential (NMP) was recorded from the septum.
      The resulting functions also increased with concentration sharply. Against a
      criterion amplitude of the NMP, thresholds measured in the first experiment (and
      predictions from the LFER) correlated 0.99. The NMP seems to offer an adequate
      objective measure of sensory irritation. The LFER, although effective
      predictively, could stand to have a parameter to anticipate that molecules beyond
      a certain size fail to trigger irritation. In the present case, a cut-off of
      chemesthetic potency occurred between butyl butyrate and hexyl butyrate for the
      group of subjects, with some variation of the boundary among individuals.

PMID- 16806321
TI  - Behavioral strategies of the African ice rat Otomys sloggetti robertsi in the
      cold.
AB  - Thermoregulation in cold environments imposes great energy demands on small
      mammals. For the ice rat Otomys sloggetti robertsi, a herbivore endemic to high
      altitude alpine regions of southern Africa, these demands might be high since it
      does not hibernate and is poorly-adapted physiologically to low temperatures. We
      investigated whether ice rats modify their behavior patterns seasonally by
      recording the duration of behaviors as well as sequential transitions among
      behaviors for free-living adult males and females. Contrary to expectations,
      gender and time of day did not influence ice rat behavior in both seasons.
      However, there were marked seasonal differences in the duration of behaviors,
      with ice rats spending significantly more time foraging and basking in winter
      whereas they remained belowground in their burrows for longer periods of time in
      summer. Hoarding behavior increased significantly from summer to winter and
      females showed higher levels of hoarding in summer than males. Sequential
      analyses revealed that behaviors were strongly influenced by season. There were
      more two-way transitions in winter than in summer, indicating the occurrence of
      behavioral routines which might reduce energy expenditure. Our data suggest that
      ice rats modify their behavior in terms of the duration and sequences of
      behaviors in response to prevailing environmental conditions.

PMID- 16806322
TI  - Role of food type in yohimbine- and pellet-priming-induced reinstatement of food
      seeking.
AB  - We have recently adapted a reinstatement model, commonly used to study relapse to
      drugs of abuse, to study the role of stress and anxiety in relapse to palatable
      food seeking [Ghitza UE, Gray SM, Epstein DH, Rice KC, Shaham Y. The anxiogenic
      drug yohimbine reinstates palatable food seeking in a rat relapse model: a role
      of CRF(1) receptors. Neuropsychopharmacology [in press]]. We found that the
      anxiogenic drug yohimbine, as well as pellet-priming, reinstate food seeking in
      food restricted rats previously trained to lever press for palatable food pellets
      (25% fat, 48% carbohydrate). Here, we studied the generality of the effect of
      yohimbine and pellet priming on reinstatement of food seeking by using three
      distinct pellet types: non-sucrose carbohydrate (NSC) (5.5% fat, 60%
      carbohydrate, 4.5% fiber), fiber (0% fat, 0% carbohydrate, 91% fiber) and sucrose
      (0% fat, 91% carbohydrate, 4% fiber). Rats were placed on a restricted diet (75
      80% of daily standard food) and for 9-12 intermittent training days (9 h/day,
      every other day) lever-pressed for the food pellets under a fixed ratio-1 (20-s
      timeout) reinforcement schedule. Subsequently, the rats were given 9-10 daily
      extinction sessions during which lever-presses were not reinforced, and were then
      injected with yohimbine (0, 0.5, 1.0, 2.0 mg/kg, i.p.) or given a single food
      pellet to induce reinstatement of food seeking. Yohimbine reinstated food seeking
      previously reinforced by NSC and sucrose pellets, but had a minimal effect on
      food seeking in rats previously trained to lever press for fiber pellets. Pellet
      priming produced a greater degree of reinstatement of lever pressing in rats
      previously trained on NSC pellets than in rats trained on fiber or sucrose
      pellets. Results suggest that the magnitude of the effect of yohimbine and pellet
      priming on reinstatement of food seeking depends in part on the composition of
      the food pellets used during training.

PMID- 16806323
TI  - Reinforcing and aversive effects of caffeine measured by flavor preference
      conditioning in caffeine-naive and caffeine-acclimated rats.
AB  - Literature on the stimulus properties of caffeine in rats and humans has
      described both reinforcing and aversive effects. But some disagreement exists
      regarding whether caffeine is an effective positive reinforcer for caffeine-naive
      individuals, and how its stimulus properties change with habitual consumption.
      These experiments measured the reinforcing/aversive effects of caffeine for rats
      across a range of concentrations, assayed by conditioned aversion or preference
      for caffeine-paired flavors, and investigated changes in preference/aversion
      after extensive prior consumption. In the first two experiments, caffeine-naive
      rats were trained in sessions alternating daily between a distinctly flavored
      palatable solution (CS+) containing caffeine (0.07-0.25 mg/ml, yielding actual
      doses of approximately 4-31 mg/kg bodyweight) and a differently flavored
      palatable solution (CS-) without caffeine. In post-conditioning two-bottle choice
      tests between the CS+ and CS- flavors a clear preference/aversion function was
      apparent across the range of doses. In a third experiment, extensive acclimation
      to daily caffeine consumption prior to flavor-caffeine pairing significantly
      altered the preference/aversion function, apparently by reducing the aversiveness
      of higher doses, not increasing reinforcement by a low dose. These experiments
      provide additional evidence for an inherent reinforcing effect for naive rats,
      and also an effect of prior caffeine consumption history.

PMID- 16806324
TI  - Is expression of some behaviours associated with de-arousal in restricted-fed
      chickens?
AB  - Broiler breeder chickens show apparently abnormal behaviours when subjected to
      routine quantitative food restriction during rearing. By using a combination of
      videorecording and radiotelemetry, this experiment addressed the question of
      whether such behaviours are associated with de-arousal. In each of 2 years, 3
      female chickens had radiotelemetry devices (Data Sciences) implanted surgically
      at 12 weeks of age, for measuring putative physiological indices of arousal
      (heart rate, blood pressure, body temperature, telencephalic EEG). Subsequently,
      when caged individually and moving freely, they were monitored over 2 days when
      their daily food ration (60 g pellets provided at 0900 h) was all eaten in <10
      min. Their behaviour (nine categories) and arousal indices were recorded in every
      minute during the photoperiod (0700 to 1900 h), using special computer software
      for videorecording (Noldus) and radiotelemetry (Dataquest LabPRO) analyses. Most
      time was spent in behaviour categories stand, push bar and feeder directed. Heart
      rate, blood pressure, body temperature, and relative powers in delta (1-4 Hz) and
      theta (4-8 Hz) frequency bands of the EEG power spectrum were all highest during
      feeder directed, whereas heart rate, temperature and delta EEG were all lowest
      during stand. Judging from significant correlation coefficients between times
      spent in different behaviours and corresponding physiological variables, across
      the day, and between ranked mean values of the 6 birds, other trends were also
      evident. For example, total time spent in all (non-food directed) oral behaviours
      was related positively to an index of de-arousal (slow wave EEG) and negatively
      to an index of arousal (heart rate). Collectively, however, these results provide
      apparently conflicting evidence of both arousal and de-arousal being associated
      with every behaviour analysed. This conclusion is explicable if abnormal
      behaviours are related to arousal in a homeostatic way [Savory, C.J., Kostal, L.
      Temporal patterning of oral stereotypies in restricted-fed fowls: 1.
      Investigations with a single daily meal. Int. J. Comp. Psychol. 1996, 9:117
      139.], being both stimulated by it and reducing it.

PMID- 16806325
TI  - Sensory interactions through neural pathways.
AB  - The word "taste" includes olfaction and somatosensory information besides the
      proper sense of taste. Taste and somatosensory sensitivity are very close and
      overlapping in most central nervous system projection areas. The objective of the
      present paper is to review a series of experiments disclosing functional
      neurophysiological interactions between taste and somatosensory information at
      different levels.

PMID- 16806326
TI  - Identification of a low vindoline accumulating cultivar of Catharanthus roseus
      (L.) G. Don by alkaloid and enzymatic profiling.
AB  - The Madagascar periwinkle [Catharanthus roseus (L.) G. Don] is a commercially
      important horticultural flower species and is the only source of the
      monoterpenoid indole alkaloids (MIAs), vinblastine and vincristine, key
      pharmaceutical compounds used to combat a number of different cancers. The
      present study uses high performance liquid chromatography for metabolic profiling
      of the MIAs extracted from seedlings and young leaves of 50 different flowering
      cultivars of C. roseus to show that, except for a single low vindoline cultivar
      (Vinca Mediterranean DP Orchid), they accumulate similar levels of MIAs. Further
      enzymatic studies with extracts from young leaves and from developing seedlings
      show that the low vindoline cultivar has a 10-fold lower tabersonine-16
      hydroxylase activity than those of C. roseus cv. Little Delicata. It is concluded
      that rapid metabolic and more selective enzymatic profiling of Catharanthus
      mutants could be useful for the identification of a range of altered MIA
      biosynthesis lines.

PMID- 16806327
TI  - The absolute configuration of (-)-3-hydroxy-alpha-calacorene.
AB  - 3-Hydroxy-alpha-calacorene was identified in extracts from cold-shocked seedlings
      of cotton (Gossypium hirsutum L.) and kenaf (Hibiscus cannabinus L.), both of
      which are members of the Malvaceae family. (-)-3-Hydroxy-alpha-calacorene was
      isolated from Heterotheca inuloides Cass. (Asteraceae). HPLC on a chiral
      stationary phase column showed that the 3-hydroxy-alpha- calacorene from cotton
      and kenaf had the same relative configuration, while that from H. inuloides was
      of the opposite configuration. X-ray crystallographic analysis established the
      absolute configuration of the compound in H. inuloides as (8R)-(-)-3-hydroxy
      alpha-calacorene.

PMID- 16806328
TI  - Bioassay-guided isolation of aldose reductase inhibitors from Artemisia
      dracunculus.
AB  - An ethanolic extract of Artemisia dracunculus L. having antidiabetic activity was
      examined as a possible aldose reductase (ALR2) inhibitor, a key enzyme involved
      in diabetic complications. At 3.75 microg/mL, the total extract inhibited ALR2
      activity by 40%, while quercitrin, a known ALR2 inhibitor, inhibited its activity
      by 54%. Bioactivity guided fractionation and isolation of the compounds that
      inhibit ALR2 activity was carried out with the total ethanolic extract yielding
      four bioactive compounds with ALR2 inhibitory activity ranging from 58% to 77% at
      3.75 microg/mL. Using LC/MS, (1)H NMR, (13)C NMR and 2D NMR spectroscopic
      analyses, the four compounds were identified as 4,5-di-O-caffeoylquinic acid,
      davidigenin, 6-demethoxycapillarisin and 2',4'-dihydroxy-4
      methoxydihydrochalcone. This is the first report on their isolation from A.
      dracunculus and the ALR2 inhibitory activity of 4,5-di-O-caffeoylquinic acid, 6
      demethoxycapillarisin and 2',4'-dihydroxy-4-methoxydihydrochalcone. These results
      suggest a use of the extract of A. dracunculus for ameliorating diabetic
      complications.

PMID- 16806329
TI  - Isolation and structure elucidation of cytotoxic polyacetylenes and polyenes from
      Echinacea pallida.
AB  - Bioassay-guided fractionation of n-hexane extracts of Echinacea pallida
      (Asteraceae) roots led to the isolation and structure elucidation of two
      polyacetylenes (1, 3) and three polyenes (2, 4, 5). Two are known hydroxylated
      compounds, namely 8-hydroxy-pentadeca-(9E)-ene-11,13-diyn-2-one (1) and 8-hydroxy
      pentadeca-(9E,13Z)-dien-11-yn-2-one (2). Two dicarbonylic constituents, namely
      pentadeca-(9E)-ene-11,13-diyne-2,8-dione (3) and pentadeca-(9E,13Z)-dien-11-yne
      2,8-dione (4), were isolated and characterized for the first time. Furthermore,
      the structure elucidation of pentadeca-(8Z,13Z)-dien-11-yn-2-one (5) is
      described. The structure of the compounds isolated was determined on the basis of
      UV, IR, NMR (including 1D and 2D NMR experiments, such as 1H-1H gCOSY, gHSQC
      DEPT, gHMBC, gNOESY) and MS spectroscopic data. The cytotoxic activity of the
      isolated constituents against MIA PaCa-2 human pancreatic adenocarcinoma cells
      was evaluated in the concentration range 1-100 microg/ml. Results show that the
      hydroxylated compounds (1, 2) have low cytotoxicity, while the more hydrophobic
      polyacetylenes (3) and polyenes (4, 5) displayed moderate activity.

PMID- 16806330
TI  - The phytoalexins from cauliflower, caulilexins A, B and C: isolation, structure
      determination, syntheses and antifungal activity.
AB  - Our continuous search for phytoalexins from crucifers led us to examine
      phytoalexin production in florets of cauliflower (Brassica oleracea var.
      botrytis) under abiotic (UV light) elicitation. Four known (isalexin, S-(-)
      spirobrassinin, 1-methoxybrassitin, brassicanal C) and three new (caulilexins A
      C) phytoalexins were isolated. The syntheses and antifungal activity of
      caulilexins A-C against the economically important pathogenic fungi Leptosphaeria
      maculans, Rhizoctonia solani and Sclerotinia sclerotiorum, and the first
      synthesis of brassicanal C are reported.

PMID- 16806331
TI  - Identification of Taylorella equigenitalis responsible for contagious equine
      metritis in equine genital swabs by direct polymerase chain reaction.
AB  - A direct-PCR assay was developed for the rapid detection of Taylorella
      equigenitalis, a Gram-negative bacterium responsible for contagious equine
      metritis (CEM) in Equidae. The bacteria may be detected in equine genital swabs
      without need for a preliminary step of DNA extraction or bacterial isolation.
      Specificity was determined with 125 isolates of T. equigenitalis, 24 isolates of
      Taylorella asinigenitalis, five commensal bacteria of the genital tract and a
      facultative intracellular pathogen of foals found in large concentration in soil.
      Our PCR is specific and amplified a 413-bp 16S ribosomal DNA product only in all
      T. equigenitalis.

PMID- 16806332
TI  - Sex- and age-related differences in rabies immunoglobulin hypersensitivity.
AB  - We retrospectively reviewed 72132 patients who had received rabies immunoglobulin
      between 1987 and 2005 at the Queen Saovabha Memorial Institute, Bangkok. Purified
      equine rabies immunoglobulin (ERIG) was given to 42965 (59.56%) patients and
      human rabies immunoglobulin (HRIG) to 29167 (40.44%) patients. A total of 812
      patients from both groups (1.13%) reported adverse reactions; among those who had
      received ERIG, 43.13% were male and 56.87% were female, and among those who had
      received HRIG, 34.62% were male and 65.38% were female. Females were at higher
      risk of exhibiting ERIG or HRIG hypersensitivity than males (P<0.01). None of the
      reactions was life-threatening. Serum sickness-like reactions to ERIG and HRIG
      were rare under the age of 10 years (0.05 and 0.01% among recipients in that age
      group).

PMID- 16806333
TI  - Human tapeworms in north Vietnam.
AB  - Sixty-five Taenia samples were collected from patients in a referral hospital in
      Hanoi, north Vietnam, for species identification by morphological and molecular
      techniques. PCR-RFLP of a mitochondrial 12S rDNA fragment, developed for this
      study, allowed direct differentiation between all Taenia spp., overcoming the
      disadvantages of classical morphological examination, which failed on
      disintegrated samples. Taenia saginata asiatica was the most common species
      (55.4%) followed by T. saginata (38.5%) and T. solium (6.2%). This report
      demonstrates the complexity of the epidemiology of Taenia spp. in Vietnam and the
      need for further work to reveal transmission patterns of these species.

PMID- 16806334
TI  - PCR-RFLP method for the identification of four members of the Anopheles annularis
      group of mosquitoes (Diptera: Culicidae).
AB  - The Anopheles annularis group of mosquitoes is widely distributed in Southeast
      Asia and may be locally important as malaria vectors. Members of this group are
      morphologically very similar and often difficult to distinguish, particularly A.
      nivipes and A. philippinensis. We report the sequence analysis of the rDNA
      internal transcribed spacer 2 (ITS2) and Domain-3 (D3) regions of the four
      members of the A. annularis group -A. nivipes, A. philippinensis, A. annularis
      and A. pallidus - and a method for their molecular identification. No
      intraspecies sequence variation was detected among the specimens, while
      interspecific sequence differences were greater for ITS2 than the D3 regions.
      Comparison of the D3 sequences of the four species revealed two SmaI restriction
      sites in A. nivipes, but only one site in A. philippinensis, A. annularis and A.
      pallidus. The ApaI site was present in both A. philippinensis and A. pallidus,
      while an NcoI site was present in A. pallidus only. Restriction digestion of the
      PCR products of D3 fragment individually with SmaI, ApaI and NcoI produced a
      distinctive pattern for all the four species. We present, for the first time, a
      PCR-RFLP method to distinguish the four members of the A. annularis group of
      mosquitoes.

PMID- 16806335
TI  - Toxicity due to organophosphorus compounds: what about chronic exposure?
AB  - The inappropriate use of toxic chemicals is common in developing countries, where
      it leads to excessive exposure and high risks of unintentional poisoning. The
      risks are particularly high with the pesticides used in agriculture, where poor
      rural populations live and work in close proximity to these compounds, which are
      often stored in and around the home. It is estimated that 99% of all deaths from
      pesticide poisoning occur in developing countries. Whilst the acute toxicity of
      pesticides has been well documented, there is still relatively little known of
      the effects on health of chronic pesticide exposure. Organophosphate insecticides
      have been extensively used in agriculture in developing countries, with little
      protection for the communities and individuals thus exposed. Given the
      indisputable chronic exposure of vulnerable groups to organophosphate compounds,
      including pregnant women, the fetus and young children, the potential for
      widespread adverse effects is considerable. Thus, whilst there is some evidence
      that chronic exposure may have adverse effects on health, there is an urgent need
      for high-quality observational and interventional studies of both occupational
      and environmental exposure to these compounds.

PMID- 16806336
TI  - Tibolone exerts progestational inhibition of matrix metalloproteinase expression
      in human endometrial stromal cells.
AB  - Tibolone and its metabolites were evaluated on matrix metalloproteinase (MMP)
      expression in human endometrial stromal cells (HESCs) under the hypothesis that
      these steroids would act as progestins on MMP-1, -2, and -3 expression. After 7
      days of priming and 24h experimental incubation of confluent cultured HESCs, 10(
      7) M medroxyprogesterone acetate (P) reduced MMP-1 to 49+/-34% (p<0.05) and MMP-3
      to 33+/-22% of basal levels (mean+/-S.E.M., p<0.05, n=5). Although HESCs were
      unaffected by 10(-8) M estradiol (E), E+P reduced MMP-1 and MMP-3 levels an
      additional 2.5-fold from P alone. Tibolone and Delta-4 tibolone were equivalent
      to E+P in inhibiting MMP-1 and MMP-3 output, whereas 10(-6)M of 3alpha-OH or
      3beta-OH tibolone was required to elicit significant inhibition of both MMPs
      (p<0.05). By contrast, none of the treatments affected HESC-secreted MMP-2
      output. The ELISA results were confirmed by Western blotting and by substrate gel
      zymography. Quantitative RT-PCR demonstrated corresponding changes in MMP-1 and
      MMP-3 mRNA levels. Inhibition of MMP-1 and MMP-3 expression by tibolone and Delta
      4 tibolone is consistent with the metabolism of tibolone to Delta-4 tibolone, and
      subsequent binding of Delta-4 tibolone to the progesterone receptor. Since 3alpha
      OH and 3beta-OH tibolone bind exclusively to the estrogen receptor, their
      inhibition of MMP-1 and MMP-3 suggests metabolism by HESCs to Delta-4 tibolone.
      These observations help to explain the paradox that the endometrium becomes
      atrophic after tibolone administration despite the persistence in the circulation
      of 3alpha-OH and 3beta-OH tibolone, but not tibolone or Delta-4 tibolone.

PMID- 16806337
TI  - Effects of 17beta-estradiol on growth and apoptosis in human vascular endothelial
      cells: influence of mechanical strain and tumor necrosis factor-alpha.
AB  - Vascular endothelial cell (EC) integrity is key to arterial health; endothelial
      dysfunction is linked to atherogenesis. Atherosclerosis shows a male
      preponderance, possibly related to the protective effect of estrogens in women.
      This study examined the effect of estrogens on growth, apoptosis and adhesion
      molecule expression in cultured human EC. The effects of 17beta-estradiol (E2)
      were studied in human umbilical vein endothelial cells (HUVEC) under normal
      culture conditions, and following exposure to cyclic mechanical strain or tumor
      necrosis factor alpha (TNFalpha). E2 enhanced HUVEC growth in serum-enriched
      media, in a concentration-dependent manner. This up-regulation of EC growth by E2
      was associated with an increase in telomerase activity, assessed by PCR-based
      TRAP analysis. Cyclic strain enhanced [(3)H]-thymidine incorporation into DNA,
      and increased activation of mitogen-activated protein (MAP) kinase ERK1/2 and
      expression of early growth genes (Egr-1 and Sp-1); E2 attenuated the strain
      induced ERK1/2 activation but not the early growth gene expression or DNA
      synthesis. TNFalpha (20 ng/mL) induced apoptosis in HUVEC, causing a decrease in
      DNA synthesis, increase in floating and Annexin-V-stained cell numbers, and
      morphological changes. TNFalpha also upregulated ERK1/2 activity and expression
      of adhesion molecules (ICAM-1, VCAM-1 and E-selectin). E2 significantly
      attenuated the effects of TNFalpha on ERK1/2 activity, apoptosis, and E-selectin
      expression in the cells. Thus, estradiol enhances growth and reduces TNFalpha
      induced apoptosis in EC; enhanced EC growth may be mediated via upregulation of
      telomerase activity. These effects are possible cellular mechanisms underlying
      female gender-associated cardiovascular protection.

PMID- 16806338
TI  - Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats
      after oral administration.
AB  - 3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in
      sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal
      activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In
      this study, the toxicokinetics and biotransformation of 4-MBC were characterized
      in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per
      group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn
      oil. Metabolites formed were characterized and the kinetics of elimination for 4
      MBC and its metabolites from blood and with urine were determined. Metabolites of
      4-MBC were characterized by (1)H NMR and LC-MS/MS as 3-(4
      carboxybenzylidene)camphor and as four isomers of 3-(4
      carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the
      camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major
      metabolite. After oral administration of 4-MBC, only very low concentrations of 4
      MBC were present in blood and the peak concentrations of 3-(4
      carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC;
      blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the
      limit of detection. Blood concentration of 4-MBC and 3-(4
      carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then
      decreased with half-lives of approximately 15 h. No major differences in peak
      blood levels between male and female rats were seen. In urine, one isomer of 3-(4
      carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4
      carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4
      carboxybenzylidene)camphor were only minor metabolites excreted with urine.
      However, urinary excretion of 4-MBC-metabolites represents only a minor pathway
      of elimination for 4-MBC, since most of the applied dose was recovered in feces
      as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4
      carboxybenzylidene)-6-hydroxycamphor. Glucuronides of both metabolites were also
      present in feces, but partly decomposed during sample workup and were thus not
      quantified. The results show that absorbed 4-MBC undergoes extensive first-pass
      biotransformation in rat liver resulting in very low blood levels of the parent 4
      MBC. Enterohepatic circulation of glucuronides derived from the two major 4-MBC
      metabolites may explain the slow excretion of 4-MBC metabolites with urine and
      the small percentage of the administered doses recovered in urine.

PMID- 16806339
TI  - Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl
      chloride or dichloroacetic anhydride.
AB  - Dichloroacetyl chloride (DCAC) is formed from trichloroethene (TCE), which is
      implicated in inducing/accelerating autoimmune response. Due to its potent
      acylating activity, DCAC may convert proteins to neo-antigens and thus could
      induce autoimmune responses. Dichloroacetic anhydride (DCAA), which is a similar
      acylating agent, might also induce autoimmune responses. To evaluate if
      chloroacylation plays a role in the induction of autoimmunity, we have measured
      the autoimmune responses following treatment with DCAC or DCAA in autoimmune
      prone MRL+/+ mice. Five-week-old female mice were injected intraperitoneally
      (twice weekly) with 0.2 mmol/kg of DCAC or DCAA in corn oil for 6 weeks. Total
      serum IgG, IgG1, and IgE levels were significantly increased in DCAC-treated mice
      as compared to controls. These increases corresponded with increases in DCAC
      specific IgG and IgG1 levels. Total serum IgM was decreased in both DCAC- and
      DCAA-treated mice. Antinuclear antibodies, measured as an indication of systemic
      autoimmune responses, were increased in both DCAC- and DCAA-treated mice. Of
      eight Th1/Th2 cytokines measured in the serum, only IL-5 was significantly
      decreased in both treatment groups. The cytokine secretion patterns of splenic
      lymphocytes after stimulation with antibodies against CD3 (T cell receptor
      mediated signal) and CD28 (costimulatory signal) differed between treatment and
      control groups. Levels of IL-1, IL-3, IL-6, IFN-gamma, G-CSF, and KC were higher
      in cultures of stimulated splenocytes from either DCAC- or DCAA-treated mice than
      from controls. The level of IL-17 was only increased in cultures from DCAC
      treated mice. Increased lymphocytic populations were found in the red pulp of
      spleens following treatment with either DCAC or DCAA. In addition, thickening of
      the alveolar septa in the lungs of DCAC- or DCAA-treated mice was observed. The
      lung histopathology in exposed mice was consistent with the symptomology observed
      in welders exposed to DCAC/phosgene. Thickening was more pronounced in DCAC
      treated mice. Our data suggest that DCAC and DCAA elicit autoimmune responses in
      MRL+/+ mice that might be reflective of their chloroacylation potential in vivo.

PMID- 16806340
TI  - Effect of plasma homocysteine level and urinary monomethylarsonic acid on the
      risk of arsenic-associated carotid atherosclerosis.
AB  - Arsenic-contaminated well water has been shown to increase the risk of
      atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may
      modify the risk by interfering with the biomethylation of ingested arsenic. In
      this study, we assessed the effect of plasma homocysteine level and urinary
      monomethylarsonic acid (MMA(V)) on the risk of atherosclerosis associated with
      arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls
      were studied. Lifetime cumulative arsenic exposure from well water for study
      subjects was measured as index of arsenic exposure. Homocysteine level was
      determined by high-performance liquid chromatography (HPLC). Proportion of MMA(V)
      (MMA%) was calculated by dividing with total arsenic species in urine, including
      arsenite, arsenate, MMA(V), and dimethylarsinic acid (DMA(V)). Results of
      multiple linear regression analysis show a positive correlation of plasma
      homocysteine levels to the cumulative arsenic exposure after controlling for
      atherosclerosis status and nutritional factors (P < 0.05). This correlation,
      however, did not change substantially the effect of arsenic exposure on the risk
      of atherosclerosis as analyzed in a subsequent logistic regression model.
      Logistic regression analyses also show that elevated plasma homocysteine levels
      did not confer an independent risk for developing atherosclerosis in the study
      population. However, the risk of having atherosclerosis was increased to 5.4-fold
      (95% CI, 2.0-15.0) for the study subjects with high MMA% (> or =16.5%) and high
      homocysteine levels (> or =12.7 micromol/l) as compared to those with low MMA%
      (<9.9%) and low homocysteine levels (<12.7 micromol/l). Elevated homocysteinemia
      may exacerbate the formation of atherosclerosis related to arsenic exposure in
      individuals with high levels of MMA% in urine.

PMID- 16806341
TI  - Methyl-beta-cyclodextrin enhances the susceptibility of human breast cancer cells
      to carboplatin and 5-fluorouracil: involvement of Akt, NF-kappaB and Bcl-2.
AB  - The response rates of extensively used chemotherapeutic drugs, carboplatin (Carb)
      or 5-fluorouracil (5-FU) are relatively disappointing because of considerable
      side effects associated with their high-dose regimen. In the present study, we
      determined whether treatment with a cholesterol depleting agent, methyl-beta
      cyclodextrin (MCD), enhances the weak efficacy of low doses of Carb or 5-FU in
      human breast cancer cells. Data demonstrate that pretreatment with MCD
      significantly potentiates the cytotoxic activity of Carb and 5-FU in both MCF-7
      and MDA-MB-231. Furthermore, we explored the molecular basis of enhanced
      cytotoxicity, and our data revealed that low-dose treatment with these drugs in
      MCD pretreated cells exhibited significantly decreased Akt phosphorylation, NF
      kappaB activity and down-regulation in expression of anti-apoptotic protein Bcl
      2. In addition, MCD pretreated cells demonstrated an increased intracellular drug
      accumulation as compared to cells treated with drugs alone. Taken together, our
      data provide the basis for potential therapeutic application of MCD in
      combination with other conventional cytotoxic drugs to facilitate reduction of
      drug dosage that offers a better chemotherapeutic approach with low toxicity.

PMID- 16806342
TI  - Monomethylarsonous acid induces transformation of human bladder cells.
AB  - Arsenic is a human bladder carcinogen. Arsenic is methylated to both monomethyl
      and dimethyl metabolites which have been detected in human urine. The trivalent
      methylated arsenicals are more toxic than inorganic arsenic. It is unknown if
      these trivalent methylated metabolites can directly cause malignant
      transformation in human cells. The goal of this study is determine if
      monomethylarsonous acid (MMA(III)) can induce malignant transformation in a human
      bladder urothelial cell line. To address this goal, a non-tumorigenic human
      urothelial cell line (UROtsa) was continuously exposed to 0.05 muM MMA(III) for
      52 weeks. Hyperproliferation was the first phenotypic change observed in exposed
      UROtsa (URO-MSC). After 12 weeks of exposure, doubling time had decreased from 42
      h in unexposed control cells to 27 h in URO-MSC. Hyperproliferation continued to
      be a quality possessed by the URO-MSC cells after both 24 and 52 weeks of
      exposure to MMA(III), which had a 40-50% reduction in doubling time. Throughout
      the 52-week exposure, URO-MSC cells retained an epithelial morphology with subtle
      morphological differences from control cells. 24 weeks of MMA(III) exposure was
      required to induce anchorage-independent growth as detected by colony formation
      in soft agar, a characteristic not found in UROtsa cells. To further substantiate
      that malignant transformation had occurred, URO-MSC cells were tested after 24
      and 52 weeks of exposure to MMA(III) for the ability to form tumors in SCID mice.
      Enhanced tumorigenicity in SCID mouse xenografts was observed after 52 weeks of
      treatment with MMA(III). These observations are the first demonstration of
      MMA(III)-induced malignant transformation in a human bladder urothelial cell line
      and provide important evidence that MMA(III) may be carcinogenic in human
      tissues.

PMID- 16806343
TI  - Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: role
      of nonoxidative metabolism.
AB  - Chronic alcohol abuse, a major health problem, causes liver and pancreatic
      diseases and is known to impair hepatic alcohol dehydrogenase (ADH). Hepatic ADH
      catalyzed oxidation of ethanol is a major pathway for the ethanol disposition in
      the body. Hepatic microsomal cytochrome P450 (CYP2E1), induced in chronic alcohol
      abuse, is also reported to oxidize ethanol. However, impaired hepatic ADH
      activity in a rat model is known to facilitate a nonoxidative metabolism
      resulting in formation of nonoxidative metabolites of ethanol such as fatty acid
      ethyl esters (FAEEs) via a nonoxidative pathway catalyzed by FAEE synthase.
      Therefore, the metabolic basis of ethanol-induced cytotoxicity was determined in
      HepG2 cells and recombinant HepG2 cells transfected with ADH (VA-13), CYP2E1
      (E47) or ADH + CYP2E1 (VL-17A). Western blot analysis shows ADH deficiency in
      HepG2 and E47 cells, compared to ADH-overexpressed VA-13 and VL-17A cells.
      Attached HepG2 cells and the recombinant cells were incubated with ethanol, and
      nonoxidative metabolism of ethanol was determined by measuring the formation of
      FAEEs. Significantly higher levels of FAEEs were synthesized in HepG2 and E47
      cells than in VA-13 and VL-17A cells at all concentrations of ethanol (100-800
      mg%) incubated for 6 h (optimal time for the synthesis of FAEEs) in cell culture.
      These results suggest that ADH-catalyzed oxidative metabolism of ethanol is the
      major mechanism of its disposition, regardless of CYP2E1 overexpression. On the
      other hand, diminished ADH activity facilitates nonoxidative metabolism of
      ethanol to FAEEs as found in E47 cells, regardless of CYP2E1 overexpression.
      Therefore, CYP2E1-mediated oxidation of ethanol could be a minor mechanism of
      ethanol disposition. Further studies conducted only in HepG2 and VA-13 cells
      showed lower ethanol disposition and ATP concentration and higher accumulation of
      neutral lipids and cytotoxicity (apoptosis) in HepG2 cells than in VA-13 cells.
      The apoptosis observed in HepG2 vs. VA-13 cells incubated with ethanol appears to
      be mediated by release of mitochondrial cytochrome c via activation of caspase-9
      and caspase-3. These results strongly support our hypothesis that diminished
      hepatic ADH activity facilitates nonoxidative metabolism of ethanol and the
      products of ethanol nonoxidative metabolism cause apoptosis in HepG2 cells via
      intrinsic pathway.

PMID- 16806344
TI  - Complete mitochondrial DNA sequence of a Conoidean gastropod, Lophiotoma
      (Xenuroturris) cerithiformis: gene order and gastropod phylogeny.
AB  - We have determined the first complete nucleotide sequence of the mitochondrial
      genome of a venomous mollusc, the Conoidean gastropod, Lophiotoma (Xenuroturris)
      cerithiformis. It is 15,380 nucleotide pairs (ntp) and encodes 13 proteins, two
      ribosomal RNAs and 22 tRNAs of the mitochondrion's own protein synthesizing
      system. The protein mRNAs, ribosomal RNAs and 13 of the tRNAs are transcribed
      from the same strand, the remaining tRNAs from the other strand. The longest
      segment of unassigned sequence is 139 ntp and includes a 82 ntp segment that is a
      perfect inverted repeat sequence of 37 ntp separated by 8 nt. The gene
      arrangement of L. cerithiformis mtDNA shows remarkable similarity to the gene
      arrangements of mtDNAs of the vetigastropod Haliotis rubra, the polyplacophoran
      Katharina tunicata and the cephalopod Octopus vulgaris, but differs dramatically
      from the gene arrangements found in the mtDNAs of pulmonate and opisthobranch
      gastropods, as well as mtDNAs of bivalves and scaphopods. A single sixteen gene
      inversion that distinguishes L. cerithiformis mtDNA from mtDNAs of H. rubra, K.
      tunicata and O. vulgaris is shared by mtDNA of a littorinomorph gastropod
      Littorina saxitalis, suggesting a close relationship of conoidean and
      littorinomorph gastropods.

PMID- 16806345
TI  - A novel method to design sparse linear arrays for ultrasonic phased array.
AB  - In ultrasonic phased array testing, a sparse array can increase the resolution by
      enlarging the aperture without adding system complexity. Designing a sparse array
      involves choosing the best or a better configuration from a large number of
      candidate arrays. We firstly designed sparse arrays by using a genetic algorithm,
      but found that the arrays have poor performance and poor consistency. So, a
      method based on the Minimum Redundancy Linear Array was then adopted. Some
      elements are determined by the minimum-redundancy array firstly in order to
      ensure spatial resolution and then a genetic algorithm is used to optimize the
      remaining elements. Sparse arrays designed by this method have much better
      performance and consistency compared to the arrays designed only by a genetic
      algorithm. Both simulation and experiment confirm the effectiveness.

PMID- 16806346
TI  - Doppler-shifted cyclotron, doppleron-phonon, and pseudo-doppleron-phonon
      resonances in indium.
AB  - Ultrasonic investigations have been carried out in geometry of the experiment
      corresponding to acoustic analogy of the Faraday effect with the use of a super
      pure crystal like indium. Lowering the temperature from 4.2 K to 1.28 K has
      revealed new peculiarities of in the magnetic field dependences of absorption and
      phase velocity of circularly polarized ultrasonic waves. The peculiarities have
      been interpreted as manifestation of multiple doppleron-phonon and Doppler
      shifted cyclotron resonances. The discovery of these resonances has changed
      interpretation of some anomalies observed in the previous experiments.

PMID- 16806347
TI  - Determine mechanical properties of particulate composite using ultrasound
      spectroscopy.
AB  - It is known that microscopic spherulite growth plays an important role in
      macroscopical properties such as elastic moduli of some semicrystalline polymers.
      Ultrasonic spectroscopy can be used to quantitatively determine the role of
      spherulites. As a first approximation, spherulitic polymers are modeled as a
      material with spherical inclusions in an amorphous matrix. This two-phase
      composite model is then physically realized by embedding glass micro-spheres in
      an epoxy. The dynamic mechanical properties of these composites are
      experimentally determined by measuring their acoustic properties such as phase
      velocity and attenuation. Acoustic scattering theories are then applied to this
      model to test their predictive capabilities for the real composite's mechanical
      properties.

PMID- 16806348
TI  - Dynamic interaction of anti-plane shear waves with arc-shaped interfacial crack
      in piezoelectric media.
AB  - The dynamic interaction between anti-plane shear waves with arc-shaped
      interfacial crack of piezoelectric media is considered here. The region of the
      debonding is modeled as an arc-shaped interfacial crack with non-contacting
      faces. The electric permeable and impermeable boundary conditions are adopted to
      get the disturbed solution, respectively. The crack opening displacement and the
      electric potential are represented by Chebyshev polynomials and a system of
      equations is derived. The calculation results show that the piezoelectric
      coefficient has remarkable effect on the crack opening displacement.

PMID- 16806349
TI  - Thickness vibrations of a piezoelectric plate under biasing fields.
AB  - Thickness vibrations of a piezoelectric plate under uniform initial
      thermoelectromechanical fields are investigated in this article. An exact
      solution is obtained for materials with general anisotropy. A plate of langasite,
      a relatively new piezoelectric material with strong piezoelectric coupling, is
      analyzed with imposed uniform acceleration as the biasing field as an example.
      The results show that the biasing fields have remarkable effect on the free
      vibrations of piezoelectric plate.

PMID- 16806350
TI  - Interior dynamics of subharmonious surface wave in an idealized bidimensional
      granular layer.
AB  - In this paper, high-speed photography was used to investigate the intrinsic
      dynamics of subharmonious surface wave in a vertical vibrated and idealized
      bidimensional granular layer. Using the high-speed photography, velocity fields
      of the granular layer at different stages through two cycles were obtained, which
      show the continuous particle motions during a cycle. From the velocity fields, a
      crystal structure in the wave-hollow was observed, which is reported for the
      first time. Furthermore, quantitative results of kinetic energy distribution in
      the layer were calculated, which shows temporal correspondence with the evolution
      of the wave pattern.

PMID- 16806351
TI  - Study of the elastic constants in a La0.6Sr0.4MnO3 film by means of laser
      generated ultrasonic wave method.
AB  - Two dimensional (2D) displacement field of the laser-generated ultrasonic wave is
      detected in a two-layered structure of La(0.6)Sr(0.4)MnO(3) (LSMO)/MgO system by
      means of the optical difference detection method. In order to obtain the elastic
      constants of the La(0.6)Sr(0.4)MnO(3) thin film, the displacement field of the
      laser-generated ultrasonic wave for the La(0.6)Sr(0.4)MnO(3)/MgO system is
      analyzed with finite element method (FEM). We further compare the theoretical
      simulations with the experimental results, and the elastic constants for the LSMO
      film, i.e., the Young's modulus and Poisson ratio, are obtained.

PMID- 16806352
TI  - Identification of laser-generated ultrasounds in the response of the cylinder
      over time and space.
AB  - A theoretical solution is presented to identify laser-generated ultrasounds in
      the transient response over time and space of a cylinder impacted by a laser line
      pulse. Theoretical radial displacements at various observation angles are
      obtained for an aluminum cylinder under thermoelastic regime. The corresponding
      displacements are observed experimentally by the laser ultrasonic technique. Good
      agreement is found in the time arrival, shape and relative amplitude of surface
      waves and various longitudinal and transverse bulk waves. These laser-generated
      ultrasounds are further identified by the ray trajectory analysis. This work will
      be helpful for the inverse problem of the nondestructive evaluation of cylinder
      parts.

PMID- 16806353
TI  - Individual and collective vibrational modes of nanostructures studied by
      picosecond ultrasonics.
AB  - We report on picosecond ultrasonic measurements obtained on aluminum and platinum
      nanostructures with variable dot size and lateral periodicity which realized a 2D
      phononic crystal. Performing investigations at different resolution scales, we
      have identified individual modes of vibration depending on the dot size, and mode
      of vibration strongly correlated with the bi-dimensional organization. The
      platinum dots sputtered on an aluminum layer have shown a behavior of isolated
      oscillators without any coupling between neighbor elements in this phononic
      crystal. The frequency of such normal modes, extracted from time resolved
      measurements are in good agreement with 3D finite element simulations. In
      contrast, with aluminum dot systems where the coupling is more efficient we
      observe a complex spectrum of vibrational modes related to the band structure
      induced by the bi-dimensional patterning.

PMID- 16806354
TI  - The transient response of a transversely isotropic cylinder under a laser point
      source impact.
AB  - The transient response of a transversely isotropic cylinder under a laser point
      source impact is solved theoretically. The radial displacement generated by the
      laser under the ablation regime is numerically calculated by introducing Fourier
      series expansion and two-dimensional Fourier transform. The validity of this
      theoretical solution is demonstrated on a fiber reinforced composite cylinder
      with a strong anisotropy. Experimental displacements are detected at the cylinder
      surface by the laser ultrasonic technique, and are analyzed by the ray
      trajectories. Corresponding theoretical displacements are calculated numerically
      and compared to the experimental signals. Good agreement is found. The
      diffraction effect caused by the cusp is observed in both theory and experiment.

PMID- 16806355
TI  - Probing of liquids by Bessel light beams under conditions of acousto-optical
      interactions.
AB  - The acousto-optical interactions of Bessel and Gaussian light beams with the
      ultrasonic field in liquids under the condition of Raman-Nath diffraction for the
      standing-wave mode are experimentally investigated. The main differences of
      acousto-optical interactions for Bessel and Gaussian light beams are revealed.
      The various phenomena of refraction and focusing of Bessel beam in liquids owing
      to sound-field spatial modulation are demonstrated.

PMID- 16806356
TI  - Picosecond ultrasonics time resolved spectroscopy using a photonic crystal fiber.
AB  - We present a broadband picosecond ultrasonics time resolved spectroscopy.
      Detection of picosecond coherent acoustic phonons using a wavelength continuum
      generation in a photonic crystal fiber (PCF) with femtosecond laser pulses is
      developed. Measurements are performed for selected wavelengths of a broad
      wavelength probe pulse within a bandwidth of 250 nm with an 825 nm center
      wavelength on two samples made of tungsten and of gallium arsenide.

PMID- 16806357
TI  - Acousto-electron interaction in InGaAsP/InP laser heterostructures.
AB  - The frequency modulation of the heterolaser radiation under the ultrasonic strain
      has been found out. The dynamic and static analysis of the spectral parameters
      change caused by the alternating strain has been fulfilled. A model is proposed
      for describing the experimental data, and their theoretical analysis is
      performed. It is demonstrated that the acousto-electron interaction is dominant
      under the action of surface waves in InGaAsP/InP laser heterostructures.

PMID- 16806358
TI  - Application of the laser generated focused-Lamb wave for non-contact imaging of
      defects in plate.
AB  - The laser generation method of focused-Lamb wave is expected to have high defect
      detection ability with advantages of non-contact testing. In this method, the
      laser beam is illuminated on the surface of the object through an arrayed-arc
      slit, and then the energy of the generated Lamb wave is concentrated on the focus
      point of arc. This focusing effect enables the concentration of higher wave
      intensity on the focus with better S/N ratio of signal, and has better spatial
      resolution compared to the conventional line arrayed method. This paper describes
      a 2-D imaging system using this laser generated, focused-Lamb wave combined with
      its detection by the air-coupled transducer. This technique is fully non-contact
      so it can be easily applied for the automatic inspection. The effectiveness of
      the proposed method was verified by experiments on a 1-mm thick aluminum plate
      with artificial drill-hole defect with diameters of 1mm. The 2-D image of was
      constructed by scanning and the result showed that the location and size of
      defects were clearly detected.

PMID- 16806359
TI  - Combined phase-sensitive acoustic microscopy and confocal laser scanning
      microscopy.
AB  - Combined phase-sensitive acoustic microscopy (PSAM) at 1.2 GHz and confocal laser
      scanning microscopy (CLSM) in reflection and fluorescence has been implemented
      and applied to polymer blend films and fluorescently labeled fibroblasts and
      neuronal cells in order to explore the prospects and the various contrast
      mechanisms of this powerful technique. Topographic contrast is available for
      appropriate samples from CLSM in reflection and, with significantly higher
      precision, from the acoustic phase images. Material contrast can be gained from
      acoustic amplitude V(z) graphs. In the case of the biological cells investigated,
      the optical and acoustic images are very different and exhibit different features
      of the samples.

PMID- 16806360
TI  - The ultrasonic probe for the investigating of internal object structure by
      ultrasound transmission tomography.
AB  - The main component of every device used for investigating internal object
      structure by Ultrasound Transmission Tomography (UTT) is a special ultrasonic
      probe. This paper presents the structure of model multielement ring probe for
      examining objects using this method in divergent ray projection geometry. The
      probe is made up of 1024 rectangular separate piezoelectric transducers working
      at frequency f=1.7 MHz, placed inside a ring with diameter D=30 cm and height h=9
      cm. Each element of the probe is equipped with a quarter-wave matching layer. All
      the transducers function as transmitters and receivers, and can be joined in
      groups both during transmitting and during receiving. Some examples of admittance
      characteristics of a single piezoelectric transducer and examples of shapes of
      pulses generated and received by particular transducers were presented. Important
      factors affecting the measurement resolution are the sizes of the active surface
      of the transducers.

PMID- 16806361
TI  - Mechanism of O2-accelerated sonolysis of bisphenol A.
AB  - The effects of dissolved gases on the sonochemical degradation of bisphenol A
      (BPA) were studied at a frequency of 500 kHz. BPA degradation rate increased in
      the order O(2)>Ar>air>N(2). The rate constant for oxygen (2.6 h(-1)) was
      approximately two fold higher than that for argon (1.2 h(-1)). A primary
      intermediate (2,3-dihydro-2-methylbenzofuran), a typical intermediate of BPA
      formed during attack by OH radicals, was detected only in the presence of oxygen,
      revealing that a different reaction path was responsible for the enhancement of
      decomposition.

PMID- 16806362
TI  - Study of polarization control model for piezoelectric actuator.
AB  - A major deficiency of piezoelectric actuator is that their control accuracy is
      seriously limited by hysteresis. In this paper, the reason why hysteresis can be
      reduced by controlling polarization is explained according to the analysis of
      microscopic polarization mechanism and domain wall theory of piezoelectric
      actuator. The reason of occurring hysteresis in voltage control mode is also
      given. Then a control model based polarization is derived. In order to evaluate
      its effectiveness, the control method based on polarization is realized by
      controlling the charge of piezoelectric actuator. The experimental results show
      that the polarization control method is significantly more linear and less
      hysteresis than the voltage control method.

PMID- 16806363
TI  - Use of the application of heterodyne laser interferometer in power ultrasonics.
AB  - We are particularly interested in the measurement of nonlinear acoustic waves in
      air, within the range of the Raman-Nath diffraction regime. We used a heterodyne
      laser interferometric system with a Bragg cell frequency of 80 MHz. A harmonic
      power acoustic wave with a frequency in the range of 20 kHz was generated, but
      higher harmonics appear when nonlinear propagation occurs in restricted volumes
      or waveguides. This topic raises a number of interesting questions. The most
      complex problem arises when processing an extremely wide-band output signal from
      a photo-detector, where the signal contains a huge number of high amplitude
      harmonics in a measured acoustic signal. The wide-band output signal from
      nonlinear wave measurement was simulated by means of similar wide-band output
      signals obtained by measuring known dynamic mechanical displacements. Because the
      frequency band of common analog circuits used for signal processing is too
      narrow, the output signal from the interferometer was digitalized and processed.
      This paper discusses the results of these tests and provides estimates of the
      frequency restrictions of signal processing.

PMID- 16806364
TI  - Temperature dependences of relaxation time, adiabatic and isothermal elastic
      moduli in ZnSe:Ni and ZnSe:Cr crystals obtained in an ultrasonic experiment.
AB  - Theory of ultrasonic absorption and dispersion, based on the Zener equation, was
      used for constructing the equations, those made it possible to restore the
      temperature dependences of relaxation time, adiabatic and isothermal elastic
      moduli on the basis of experimental data on the temperature dependences of
      ultrasound absorption and phase velocity. This method was used for processing the
      experimental results obtained in single crystals of ZnSe:Ni and ZnSe:Cr.

PMID- 16806365
TI  - Lamb waves beam deviation due to small inclination of the test structure in air
      coupled ultrasonic NDT.
AB  - In Lamb waves inspection, an air-coupled transmitter transducer is oriented at a
      specific angle such that it generates a pure Lamb mode which propagates along the
      structure and interacts with any existing defects. For this inspection system,
      amplitude losses appears when small inclinations of the tested structure occurs.
      An important factor which affects directly these losses has been observed, it
      consists of the Lamb waves beam (LWB) deviation due to this bad alignment. In
      this work, a simple expression of LWB deviation has been deduced. This expression
      includes the test structure angle, phase velocity of generated Lamb mode, and the
      phase velocity of waves propagating in the coupled medium. A(0) Lamb mode is
      generated and detected in 1 mm thick aluminium plate sample using 1 MHz PZ27
      piezoelectric transducers of 20 mm of diameter. Experimental LWB deviation angles
      are measured for different inclination angles of the test sample. A comparative
      study is released with theoretical results. For 1 degree of misalignment in the
      aluminium plate inclination, and transducers separation distance of 35 mm, LWB
      deviation angle is around 7 degrees and the amplitude is reduced by around 11%.
      Then, for a large separation distance, we must move the receiver transducer to
      detect the deviated LWB. It is shown that, for both theoretical and experimental
      studies, the LWB deviation and its measured amplitude are very sensitive to the
      alignment of the tested structure with respect to the transmitter-receiver
      transducers plane. In metal plates it is most satisfactory to use A(0) mode
      compared with S(0) mode since it is easy to excite and has a large amplitude and
      small deviation beam angles.

PMID- 16806366
TI  - A dynamical model of subharmonic generation in ultrasonic infrared thermography.
AB  - Subharmonics are often observed in ultrasonic infrared thermography (UIR) system
      as samples are excited by ultrasonic transducers, and it is testified that, as
      the subharmonics appear, the detectability of cracks or defects in the sample is
      greatly enhanced in the UIR system. A dynamical model to explore the generation
      mechanism of the subharmonics and simulate the sample motion excited by an
      ultrasonic transducer in the UIR system is presented in this paper. In the model,
      the sample is continuously impacted by the transducer as the transducer is pushed
      to the sample by a constant force, in which the sample is simplified as a damped
      oscillator and the transducer is simplified as an active oscillator with constant
      frequency and amplitude. The impact process is also taken into account, in which
      the acting force is assumed to vary linearly during the impact process. A stable
      waveform of subharmonics in the sample can be obtained in appropriate conditions.

PMID- 16806367
TI  - Propagation phenomena of wideband guided waves in a bended pipe.
AB  - Ultrasonic guided waves in pipes have been anticipated as a rapid screening
      technique for pipe inspection because of their long-range propagation due to low
      energy leakage. In this paper, the propagation phenomena of guided waves in a
      bended pipe were investigated using a wideband laser ultrasonic system. The laser
      ultrasonic system, together with wavelet transformation, is a powerful tool for
      observing the dispersive phenomena intrinsic to guided waves. Bended stainless
      steel (SUS304) pipes with 6-mm outer diameter and 1-mm wall thickness were used
      in the experiments. The bending angles of the pipes were set to 0 degrees
      (straight pipe), 10 degrees, 30 degrees, 60 degrees and 90 degrees. The radius of
      the bend was 12.5 mm in all the pipes. A Q-switched Nd:YAG laser was employed to
      generate the guided waves. The generated guided waves were detected with a
      heterodyne interferometer. The obtained time-domain signals and their wavelet
      coefficients indicated the following two conclusions: (1) The amplitude of the
      F(1,1) mode converted from the L(0,1) mode increased with the increase of the
      bending angle. (2) Mode conversions from the L(0,1) to F(1,1) modes and vice
      versa were clearly observed in the low-frequency range up to around 200 kHz.

PMID- 16806368
TI  - Parametric estimation of ultrasonic phase velocity and attenuation in dispersive
      media.
AB  - In ultrasonic characterization of liquids, gases, and solids, accurate estimation
      of frequency dependent attenuation and phase velocity is of great importance. Non
      parametric methods, such as Fourier analysis, suffers from noise sensitivity, and
      the variance of the estimated quantities is limited by the signal-to-noise ratio.
      In this paper we present a parametric method for estimation of these properties.
      Pulse echo experiments in ethane, oxygen and mixtures of the two show that the
      proposed method can estimate phase velocity and attenuation with up to 50 times
      lower variance than standard non-parametric methods.

PMID- 16806369
TI  - A new open-loop driving method of piezoelectric actuator for periodic reference
      inputs.
AB  - The hysteresis characteristic of piezoelectric actuators is one of the major
      deficiencies in a wide variety of precise tracking positioning controls. In this
      paper, a novel mathematical model is proposed to describe hysteresis precisely
      and an open-loop tracking controller is implemented with the proposed model to
      compensate the hysteresis for tracking periodic sinusoidal inputs. Finally, some
      tracking control experiments based on a micro-positioning stage for the desired
      sinusoidal trajectory are performed according to the proposed method and the
      experimental results demonstrate that the positioning precision is noticeably
      improved in the open-loop operation compared to the conventional open-loop
      control without any compensation. In comparison to the regular PID closed-loop
      controller, the proposed feedforward control method has better tracking
      performance.

PMID- 16806370
TI  - Ultrasonic spectroscopy of pure cyclic compounds.
AB  - Ultrasonic studies of the group of halogens of benzene and particularly
      dependence of acoustic parameters on the structure of organic liquids,
      demonstrate some interesting regularities in the group of these compounds in gas
      and liquid states. In this paper results for five cyclic liquids: bromo-, chloro
      , fluoro- and jodobenzene are discussed and compared to benzene. Vibrational
      relaxation was observed in all the compounds. The studies reported here as well
      as other experimental for great number of compounds support the conclusion that
      almost all vibrational relaxation processes in liquids can be described using a
      single relaxation time. It also seems that all vibrational degrees of freedom of
      the molecule take part in this vibrational process. It seems that differences in
      transition probabilities between molecules studied could be caused by additional
      attraction between of molecules having a significant dipole moments.

PMID- 16806371
TI  - Calculation of electromechanical coupling coefficient of Lamb waves in
      multilayered plates.
AB  - Two methods have been always used to calculate the electromechanical coupling
      coefficient of a Lamb wave in a multilayered plate: one is an approximate method
      using the acoustic velocity difference under different electric boundary
      conditions and the other is the Green's function method. The Green's function
      method is more accurate but more complicated, because an 8N-order matrix is used
      for calculating the electromechanical coupling coefficient of the Lamb wave in an
      N-layered plate, which induces great computation loads and some calculation
      deviations. In this paper, a transfer matrix method is used for calculating the
      electromechanical coupling coefficient of Lamb waves in a multilayered plate, in
      which only an 8-order matrix is needed regardless of the number of layers of the
      plate. The results show that the transfer matrix method can obtain the same
      accuracy as those by the Green's function method, but the computation load and
      deviation are greatly decreased by avoiding the use of a high order matrix used
      in the Green's function method.

PMID- 16806372
TI  - An ultrasonic measurement model using a multi-Gaussian beam model for a
      rectangular transducer.
AB  - To date, ultrasonic measurement models have primarily treated systems where
      circular transducers are used. Recently, however, a highly efficient ultrasonic
      beam model for a rectangular transducer has also become available where the
      transducer is represented as a superposition of a relatively few Gaussian beams.
      Thus, using the multi-Gaussian beams, we developed ultrasonic measurement models
      for systems where a rectangular transducer is employed. In this paper, we
      describe the developed models including the beam model, the efficiency factor for
      a rectangular transducer and far-field scattering models for some standard
      scatterers. Furthermore, the accuracy of the proposed model is verified by the
      comparison of the model-based predictions to the experimental measurements.

PMID- 16806373
TI  - Anomalous sea surface reverberation scale model experiments.
AB  - Low frequency sea surface sound backscattering from approximately 100 Hz to a few
      kHz observed from the 1960s broadband measurements using explosive charges to the
      Critical Sea Test measurements conducted in the 1990 s is substantially higher
      than explained by rough sea surface scattering theory. Alternative theories for
      explaining this difference range from scattering by bubble plumes/clouds formed
      by breaking waves to stochastic scattering from fluctuating bubble layers near
      the sea surface. In each case, theories focus on reverberation in the absence of
      the large-scale surface wave height fluctuations that are characteristic of a sea
      that produces bubble clouds and plumes. At shallow grazing angles, shadowing of
      bubble plumes and clouds caused by surface wave height fluctuations may induce
      first order changes in the backscattered signal strength. To understand the
      magnitude of shadowing effects under controlled and repeatable conditions, scale
      model experiments were performed in a 3 m x 1.5 m x 1.5 m tank at the Technical
      University of Denmark. The experiments used a 1 MHz transducer as the source and
      receiver, a computer controlled data acquisition system, a scale model target,
      and a surface wave generator. The scattered signal strength fluctuations observed
      at shallow angles are characteristic of the predicted ocean environment. These
      experiments demonstrate that shadowing has a first order impact on bubble plume
      and cloud scattering strength and emphasize the usefulness of model scale
      experiments for studying underwater acoustic events under controlled conditions.

PMID- 16806374
TI  - The range equation of the ultrasonic link in gas media.
AB  - The paper presents a few chosen issues concerning the conditions that must be met
      to render possible the effective use of ultrasonic waves in active and passive
      applications in various gas media. The basic parameters of the gas medium
      influencing the transmission of ultrasonic waves in this kind of medium were
      discussed. An analysis of the range equation of the ultrasonic coupler in the gas
      medium and the computer model of the link in the stationary medium conditions
      were presented. An equation for the level of power decrease in the link was
      formulated and the calculated and measured characteristics of the level of power
      decrease for a few ultrasonic transducers working in the band of 20-100 kHz were
      presented in graphs.

PMID- 16806375
TI  - Modern acoustic emission technique and its application in aviation industry.
AB  - This paper proposes the concept of modern acoustic emission (MAE) technique and
      describes its application in aviation industry. Modern AE is characterized by the
      combination of AE parameter and waveform analysis based on the understanding of
      AE source mechanism, the property of sound wave propagation and the interaction
      between sound wave and the medium in which the sound wave is propagating. Another
      feature of MAE is characterized by the application of so-called fully digital AE
      apparatus with low noise, high speed of data transmission and accurate AE source
      locating capability. MAE is merely an imagination without the realization of the
      advanced fully digital AE instrument. The application of MAE in monitoring the
      conditions of aircraft structures during a fatigue test was taken as an example
      for showing the important role played by AE. Roles of AE in the evaluation of
      (environment-related) corrosion damage of aircraft were also presented.

PMID- 16806376
TI  - Combined surface-focused acoustic microscopy in transmission and scanning
      ultrasonic holography.
AB  - Employment of ultrasound techniques in nondestructive testing may require
      identification of the acoustic modes contributing to imaging. Such identification
      can be achieved, with some restrictions, by time-of-flight analysis. Another
      approach is acoustic holography that reveals the propagation properties of any
      selected mode. In anisotropic media, the propagation features are distinct and
      allow for a reliable classification of the selected mode. Both techniques were
      applied for classification of bonded, disbonded, and weakly bonded areas in
      directly bonded semiconductor wafers.

PMID- 16806377
TI  - Parallel numerical simulation of the ultrasonic waves in a prestressed formation.
AB  - Formation stress prediction plays an important role in petroleum production.
      Understanding ultrasonic wave propagation in a stress-induced anisotropic
      formation will help us to find an efficient method to correctly predict formation
      stress or formation pore pressure. In this work, a parallel 3D finite-difference
      time domain (FDTD) method is developed to simulate elastic wave propagation in
      pre-stressed formations. A perfectly matched layer (PML) is used as an absorbing
      boundary condition. The acceleration ration of total CPU computation time and the
      lasting time of the program run in the super computer-ShenTeng 6800 in the Super
      Computation Center of Chinese Academy of Science (CAS) are tested. It shows that
      the acceleration factor of the parallel FDTD program is considerably high even if
      the domain is only divided in one direction. When the total computation model
      size fixed, the acceleration factor of 8 CPU and 64 CPU is 3.0 and 13.8,
      respectively. The velocities under various static stresses are obtained by
      processing the array data calculated with the FDTD using Prony's method. The
      linear relation between velocity and the applied pre-stress is in agreement with
      that predicted by the acoustoelasticity theory. Results from the numerical
      simulation confirm the reciprocity principle and the superposition principle.

PMID- 16806378
TI  - Characteristics of fundamental acoustic wave modes in thin piezoelectric plates.
AB  - The characteristics of the three lowest order plate waves (A(0), S(0), and SH(0))
      propagating in piezoelectric plates whose thickness h is much less than the
      acoustic wavelength lambda are theoretically analyzed. It is found that these
      waves can provide much higher values of electromechanical coupling coefficient
      K(2) and lower values of temperature coefficient of delay (TCD) than is possible
      with surface acoustic waves (SAWs). For example, in 30Y-X lithium niobate, the
      SH(0) mode has K(2)=0.46 and TCD=55 ppm/degrees C. The corresponding values for
      SAW in the widely used, strong coupling material of 128Y-X lithium niobate are
      K(2)=0.053 and TCD=75 ppm/degrees C. Another important advantage of plate waves
      is that, unlike the case of SAWs, they can operate satisfactorily in contact with
      a liquid medium, thus making possible their use in liquid phase sensors.

PMID- 16806379
TI  - Evaluation of CVD diamond coating layer using leaky Rayleigh wave.
AB  - In the present study, the possibility of using leaky Rayleigh waves as a
      nondestructive tool for the evaluation of CVD diamond coating layer is explored
      experimentally. For this purpose, a set of CVD diamond coated specimens are
      prepared and the leaky Rayleigh waves are measured in an immersion, pulse-echo
      setup. For the proper analysis of the acquired signals we propose a novel signal
      analysis approach, namely the "time trace angular scan (TTAS)" image. Then, the
      proposed approach together with the backward radiation profiles are applied for
      the analysis of signals acquired in the initial experiments. The TTAS image shows
      the entire information on both time-of-arrival and angle of incidence of the
      signals for the proper "time-angle windowing." Then, the backward radiation
      profile of the windowed signals provides adequate parameters from which
      nondestructive evaluation of the coated specimens is carried out.

PMID- 16806380
TI  - Nondestructive testing using air-borne ultrasound.
AB  - Over the last two decades, more efficient transducers were developed for the
      generation and reception of air-borne ultrasound, thus enabling the non-contact,
      non-contaminating inspection of composite laminates and honeycomb structures
      widely used in the aerospace industry. This paper presents the fundamentals of
      making air-borne ultrasonic measurement, and point out special considerations
      unique to propagating ultrasound in air and through solids. Transducer beam
      profile characterization, thickness dependence and resonance effects in the
      transmission of air-coupled ultrasound through plates, and the detection and
      imaging of defects and damage in solid laminates and honeycomb sandwich will be
      discussed and illustrated with examples. Finally, a manual scan system developed
      for implementing air-borne ultrasonic imaging in the field and on aircraft will
      be introduced.

PMID- 16806381
TI  - Observation of fluorescence emissions from single-bubble sonoluminescence in
      water doped with quinine.
AB  - Sonoluminescence is a phenomenon involving the transduction of sound into light.
      The detailed mechanism as well as the energy-focusing potentials are not yet
      fully explored and understood. So far only optical photons are observed, while
      emissions in the ultra-violet range are only inferred. By doping the fluorescent
      dye quinine into water with dilute sulphuric acid, the high energy photons can be
      converted into the optical photons with slower decay constants. These
      sonoluminescence and fluorescent emissions were observed in coincidence, and the
      emitted signals of the two modes can be differentiated by their respective timing
      profiles. Plans for using this technique as a diagnostic tool to quantitatively
      study ultra-violet and other high energy emissions in sonoluminescence are
      discussed.

PMID- 16806382
TI  - Study of a new type linear ultrasonic motor with double-driving feet.
AB  - A new type linear USM with double-driving feet has been developed. The stator
      consists of eight piezoelectric ceramic plates and one brass plate. Piezoelectric
      ceramics plates are polarized along the thickness and are symmetrically bonded to
      the two surfaces of one rectangle brass plate. Double-driving feet are assembled
      on the same side of the brass plate. The working vibration mode is a composite in
      plane bimode, which consists of the first longitudinal in-plane vibration mode
      and the second bending one. The basic size of the linear USM is determined
      carefully by FEA. The characteristics of the prototype motor were measured
      experimentally.

PMID- 16806383
TI  - A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness
      of the NY99 strain of West Nile virus.
AB  - Substitutions were engineered individually and in combinations at the fusion
      loop, receptor-binding domain and a stem-helix structure of the envelope protein
      of a West Nile virus strain, NY99, and their effects on mouse virulence and
      presentation of epitopes recognized by monoclonal antibodies (MAbs) were
      assessed. A single substitution within the fusion loop (L107F) attenuated mouse
      neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The
      L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose
      epitope had not been previously identified. MAb 3D9 was subsequently shown to be
      broadly cross-reactive with other flaviviruses, consistent with binding near the
      highly conserved fusion loop.

PMID- 16806384
TI  - Adeno-associated virus (AAV) capsid genes isolated from rat and mouse liver
      genomic DNA define two new AAV species distantly related to AAV-5.
AB  - Using polymerase chain reactions and genome walking strategies, adeno-associated
      virus (AAV)-like capsid genes were isolated from rat and mouse liver genomic DNA,
      where they are present at <5 copies per cell. These genes define two new species
      of AAVs since their amino acid sequences are <60% identical to each other or to
      any other AAV capsid. They are most similar to the AAV-5 and goat AAV capsids. A
      recombinant vector with the mouse AAV capsid and a lacZ transgene (rAAV-mo.1
      lacZ) was able to transduce rodent cell lines in vitro. However, it was not able
      to transduce eight human cell lines or primary human fibroblasts in vitro. It did
      not bind heparin and its ability to transduce cells in vitro was not inhibited by
      heparin, mucin, or sialic acid suggesting it uses a novel entry receptor. rAAV
      mo.1 lacZ was 29 times more resistant to in vitro neutralization by pooled,
      purified human IgG than AAV-2. In vivo, rAAV-mo.1 lacZ efficiently transduced
      murine ocular cells after a subretinal injection. Intramuscular injection of a
      rAAV-mo.1 human factor IX (hFIX) vector into mice resulted in no detectable hFIX
      in plasma, but intravenous injection resulted in high plasma levels of hFIX,
      equivalent to that obtained from a rAAV-8 hFIX vector. Biodistribution analysis
      showed that rAAV-mo.1 primarily transduced liver after an intravenous injection.
      These AAV capsids may be useful for gene transfer in rodents.

PMID- 16806385
TI  - Vaccinia virus K1L protein supports viral replication in human and rabbit cells
      through a cell-type-specific set of its ankyrin repeat residues that are distinct
      from its binding site for ACAP2.
AB  - Vaccinia virus (VV) K1L is a host-range gene and encodes a protein comprised of
      six ankyrin repeats (ANKs). We showed here that a large portion of the K1L
      protein, except ankyrin repeat 1 (ANK1) and C-terminal halves of ANK2 and ANK3,
      can be deleted or substituted with an unrelated ANK with no adverse effect on VV
      replication in human HeLa cells. In contrast, only ANK4 and ANK6 can be mutated
      without impairing VV replication in rabbit RK13 cells. The growth rate of VV in
      HeLa cells was reduced differentially by substituting phenylalanine 82 or serine
      83 of ANK2 and abolished completely by substituting both residues. These
      substitutions, however, did not affect K1L's ability to bind ACAP2, a GTPase
      activating protein for ARF6. Our data support the hypothesis that surface
      residues of a few consecutive K1L ANKs mediate the host-range function by
      interacting with protein factors that are distinct from ACAP2.

PMID- 16806386
TI  - The E5 oncoprotein of BPV-4 does not interfere with the biosynthetic pathway of
      non-classical MHC class I.
AB  - The major histocompatibility complex (MHC) class I region in mammals contains
      both classical and non-classical MHC class I genes. Classical MHC class I
      molecules present antigenic peptides to cytotoxic T lymphocytes, whereas non
      classical MHC class I molecules have a variety of functions. Both classical and
      non-classical MHC molecules interact with natural killer cell receptors and may
      under some circumstances prevent cell death by natural killer cytotoxicity. The
      E5 oncoprotein of BPV-4 down-regulates the expression of classical MHC class I on
      the cell surface and retains the complex in the Golgi apparatus. The inhibition
      of classical MHC class I to the cell surface results from both the impaired
      acidification of the Golgi, due to the interaction of E5 with subunit c of the H+
      V-ATPase, and to the physical binding of E5 to the heavy chain of MHC class I.
      Despite the profound effect of E5 on classical MHC class I, E5 does not retain a
      non-classical MHC class I in the Golgi, does not inhibit its transport to the
      cell surface and does not bind its heavy chain. We conclude that, as is the case
      for HPV-16 E5, BPV-4 E5 does not down-regulate certain non-classical MHC class I,
      potentially providing a mechanism for the escape of the infected cell from attack
      by both cytotoxic T lymphocytes and NK cells.

PMID- 16806387
TI  - Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via
      a redox-sensitive pathway.
AB  - Respiratory syncytial virus (RSV)-induced chemokine gene expression occurs
      through the activation of a subset of transcription factors, including Interferon
      Regulatory Factor (IRF)-3. In this study, we have investigated the signaling
      pathway leading to RSV-induced IRF-3 activation and whether it is mediated by
      intracellular reactive oxygen species (ROS) generation. Our results show that RSV
      infection induces expression and catalytic activity of IKKepsilon, a noncanonical
      IKK-like kinase. Expression of a kinase-inactive IKKepsilon blocks RSV-induced
      IRF-3 serine phosphorylation, nuclear translocation and DNA-binding, leading to
      inhibition of RANTES gene transcription, mRNA expression and protein synthesis.
      Treatment of alveolar epithelial cells with antioxidants or with NAD(P)H oxidase
      inhibitors abrogates RSV-induced chemokine secretion, IRF-3 phosphorylation and
      IKKepsilon induction, indicating that ROS generation plays a fundamental role in
      the signaling pathway leading to IRF-3 activation, therefore, identifying a novel
      molecular target for the development of strategies aimed to modify the
      inflammatory response associated with RSV infection of the lung.

PMID- 16806388
TI  - Visual training improves underwater vision in children.
AB  - Children in a tribe of sea-gypsies from South-East Asia have been found to have
      superior underwater vision compared to European children. In this study, we show
      that the improved underwater vision of these Moken children is not due to better
      contrast sensitivity in general. We also show that European children can achieve
      the same underwater acuity as the Moken children. After 1 month of underwater
      training (11 sessions) followed by 4 months with no underwater activities,
      European children showed improved underwater vision and distinct bursts of pupil
      constriction. When tested 8 months after the last training session in an outdoor
      pool in bright sunlight-comparable to light environments in South-East Asia-the
      children had attained the same underwater acuity as the sea-gypsy children. The
      achieved performance can be explained by the combined effect of pupil
      constriction and strong accommodation.

PMID- 16806389
TI  - Flank facilitation and contour integration: different sites.
AB  - Observers' ability to integrate features into extended contours, and to exploit
      the flanking structure to facilitate contrast detection (flank facilitation),
      exhibit a similar dependence on element spacing and orientation. Here, we
      investigate whether this reflects the operation of a common cortical mechanism by
      comparing performance for both tasks under monocular, binocular, dichoptic, and
      stereoscopic viewing conditions. Our results clearly implicate different cortical
      sites for flank-facilitated detection and contour integration; the former is a
      purely monocular phenomenon and must therefore occur at the earliest stages of
      cortical processing. In contrast, contour integration is a binocular process and
      occurs after the encoding of relative disparity, suggesting substantial extra
      striate involvement. We conclude that the sites, and therefore the mechanisms,
      underlying these two seemingly related psychophysical phenomena are different.

PMID- 16806390
TI  - Texture segregation on the basis of contrast polarity of odd-symmetric filters.
AB  - This is the first study to demonstrate the selectivity of learning for contrast
      polarity. The finding is the main result of an investigation into the existence
      of central and peripheral vision mechanisms selective for contrast polarity
      within the texture-segregation process, using the perceptual learning paradigm in
      a detection task. Energy models (Malik & Perona, 1990) exclude segregation of
      textures composed of elements of odd-symmetric luminance profile by contrast
      polarity differences. Here the target was a Gabor patch (0.8 deg) of 1 cyc/deg in
      sine phase (odd-symmetry) embedded in a background of mirror-image elements. Our
      results showed that, in fovea, segregation on the basis of contrast polarity was
      above threshold from the first session. After learning, the target popped-out in
      both central and peripheral vision for durations over 10 ms. Our major result is
      that learning is selective for contrast polarity; it is also selective for
      orientation and position, all characteristics distinctive of early processing.
      Since the learning effects were obtained with texture composed of odd-symmetric
      mirror-image elements, they indicate that the output from odd-symmetric filters
      was not excluded or inhibited in texture segmentation, but instead played an
      active role. Our data support models of texture segmentation, in which detection
      of texture gradient is achieved on the basis of early cortical process, before
      the non-linear transformation of their output.

PMID- 16806391
TI  - Peripheral defocus does not necessarily affect central refractive development.
AB  - PURPOSE: Recent experiments in monkeys suggest that deprivation, imposed only in
      the periphery of the visual field, can induce foveal myopia. This raises the
      hypothesis that peripheral refractive errors imposed by the spectacle lens
      correction could influence foveal refractive development also in humans. We have
      tested this hypothesis in chicks. METHODS: Chicks wore either full field
      spectacle lenses (+6.9 D/-7 D), or lenses with central holes of 4, 6, or 8mm
      diameter, for 4 days (n=6 for each group). Refractions were measured in the
      central visual field, and at -45 degrees (temporal) and +45 degrees (nasal), and
      axial lengths were measured by A-scan ultrasonography. RESULTS: As previously
      described, full field lenses were largely compensated within 4 days (refraction
      changes with positive lenses: +4.69+/-1.73 D, negative lenses: -5.98+/-1.78 D,
      both p<0.001, Dunnett's test, to untreated controls). With holes in the center of
      the lenses, the central refraction remained emmetropic and there was not even a
      trend of a shift in refraction (all groups: p>0.5, Dunnetts test). At +/-45
      degrees , the lenses were partially compensated despite the 4/6/8mm central
      holes; positive lenses: +2.63 / +1.44 / +0.43 D, negative lenses: -2.57 / -1.06 /
      +0.06 D. CONCLUSIONS: There is extensive local compensation of imposed refractive
      errors in chickens. For the tested hole sizes, peripherally imposed defocus did
      not influence central refractive development. To alter central refractive
      development, the unobstructed part in the central visual field may have to be
      quite small (hole sizes smaller than 4mm, with the lenses at a vertex distance of
      2-3mm).

PMID- 16806392
TI  - Neural and optical limits to visual performance in myopia.
AB  - We investigated the relative importance of neural and optical limitations to
      visual performance in myopia. A number of visual performance measures were made
      on all or subsets of 121 eyes of emmetropic and myopic volunteers aged 17-35
      years. These tests included visual measures that are mainly neurally limited
      (spatial summation out to +/-30 degrees in the horizontal visual field and
      resolution acuity out to +/-10 degrees in the horizontal visual field) and
      central ocular aberrations. We found that myopia affected the neurally limited
      tests, but had little effect on central higher order aberration. The critical
      area for spatial summation increased in the temporal visual field at 0.03 log
      units/dioptre of myopia. Resolution acuity decreased at approximately 0.012 log
      units/dioptre of myopia. Losses of visual function were slightly greater in the
      temporal than in the nasal visual field. The observed visual deficit in myopia
      can be explained by either global retinal expansion with some post-receptor loss
      (e.g. ganglion cell death) or a posterior polar expansion in which the point
      about which expansion occurs is near the centre of the previously emmetropic
      globe.

PMID- 16806393
TI  - Groundbreaking papers in water research 1967-2006. Microbiology and biochemistry
      of enhanced biological phosphate removal process.

PMID- 16806394
TI  - Screening for unicellular algae as possible bioassay organisms for monitoring
      marine water samples.
AB  - ECOTOX is an automatic early warning system to monitor potential pollution of
      freshwater, municipal or industrial waste waters or aquatic ecosystems. It is
      based on a real time image analysis of the motility and orientation parameters of
      the unicellular, photosynthetic flagellate Euglena gracilis. In order to widen
      the use of the device to marine habitats and saline waters nine marine
      flagellates were evaluated as putative bioassay organisms, viz. Dunaliella
      salina, Dunaliella viridis, Dunaliella bardawil, Prorocentrum minimum Kattegat,
      P. minimum Lissabon, Tetraselmis suecica, Heterocapsa triquetra, Gyrodinium
      dorsum and Cryptomonas maculata. Because of their slow growth the last three
      strains were excluded from further evaluation. Selection criteria were ease of
      culture, density of cell suspension, stability of motility and gravitactic
      orientation. The sensitivity toward toxins was tested using copper(II) ions. The
      instrument allows the user to automatically determine effect-concentration (EC)
      curves from which the EC(50) values can be calculated. For the interpretation of
      the EC curves a sigmoid logistic model was proposed which proved to be
      satisfactory for all tested strains. The inhibition of the motility was
      considered as the most appropriate movement parameter as an endpoint. The
      Dunaliella species had the lowest sensitivity to copper with EC(50) values of
      220, 198 and 176 mg/L for D. salina, D. bardawil and D. viridis, respectively,
      followed by T. suecica with an EC(50) value of 40 mg/L. The Prorocentrum species
      were found to be the most sensitive with an EC(50) value of 13.5 mg/L for P.
      minimum Lissabon and 7.5 mg/L for P. minimum Kattegat.

PMID- 16806395
TI  - The effect of advanced treatment on chlorine decay in metallic pipes.
AB  - Experiments were run to measure what effect advanced treatment might have on the
      kinetics of chlorine and chloramine decay in metallic pipes that comprise many
      drinking water distribution systems. A recirculating loop of 6-in diameter
      unlined ductile iron pipe was used to simulate turbulent flow conditions in a
      pipe with significant corrosion and tubercle buildup. Conventionally treated test
      water was subjected to either ozonation, carbon adsorption (GAC), reverse osmosis
      (RO) or no further treatment before being chlorinated and introduced into the
      pipeline simulator. Results showed that overall chlorine decay in the simulator
      was consistently dominated by wall reactions whose first-order rate constants
      were an order of magnitude higher than those for the bulk water. With free
      chlorine, the wall rate constants for ozonated and GAC-treated water were about
      twice those of conventional or RO-treated water. This behavior is believed due to
      the effect that changes in the organic content of water have on its ability to
      complex iron and the effect that changes in water conductivity have on pipe wall
      corrosion. Tests run with chloraminated water showed no statistically significant
      effect of treatment type and had wall rate constants that were only 40 to 70% as
      high as those using free chlorine.

PMID- 16806396
TI  - Effect of solids retention time on structure and characteristics of sludge flocs
      in sequencing batch reactors.
AB  - The effect of solids retention time (SRT) (4-20 d) on sludge floc structure, size
      distribution and morphology in laboratory-scale sequencing batch reactors
      receiving a glucose-based synthetic wastewater was studied using image analysis
      in a long-term experiment over one year. Floc size distribution (>10 microm)
      could be characterized by a log-normal model for no bulking situations, but a bi
      modal distribution of floc size was observed for modest bulking situations. In
      each operating cycle of the SBRs, the variation in food /microorganisms ratio
      (0.03-1.0) had no significant influence on floc size distribution and morphology.
      The results from a long-term study over one year showed that no clear
      relationship existed between SRT and median floc size based on frequency.
      However, sludge flocs at the lower SRTs (4-9 d) were much more irregular and more
      variable in size with time than those at higher SRTs (16 and 20 d). The level of
      effluent-suspended solids at lower SRTs was higher than that at higher SRTs.

PMID- 16806397
TI  - Photocatalytic oxidation of nitrogen oxides using TiO2 loading on woven glass
      fabric.
AB  - TiO2 loading on woven glass fabric is applied to treat nitrogen oxides (NOx) by
      photocatalytic oxidation (PCO). In this paper, the PCO behavior of NO at high
      concentrations was studied by PCO of NOx at source levels (20-168 ppm). The PCO
      efficiency reached 27% in this experiment, while the inlet NOx concentration was
      168 ppm (147 ppm NO). The dependency of the reaction rate on several key
      influencing factors (relative humidity, space time, inlet concentration, oxygen
      percentage) was also studied. The results illustrate that the resulting hydroxyl
      radical and active oxide play an important role in the oxidation of NOx. The
      reactions are limited by the thermodynamic equilibrium after ca. 15s space time.
      A possible explanation for the catalyst deactivation is the accumulation of
      nitric acid and nitrous acid on the TiO2 surface during the PCO of NOx. However,
      the photocatalytic activity can be recovered with a simple heat treatment. The
      results from the study of the effect of the inlet concentration were described
      with the Langmuir-Hinshelwood model.

PMID- 16806398
TI  - CWAO of phenol using CeO2/gamma-Al2O3 with promoter--effectiveness of promoter
      addition and catalyst regeneration.
AB  - The effect of promoter addition on activity of CeO(2)/gamma-Al(2)O(3) was
      assessed via the CWAO of phenol. Adding Cu as the promoter rendered the most
      effective performance, followed by Mn, although the performance of Mn-promoted
      catalyst was inferior to CeO(2)/gamma-Al(2)O(3). Mineralization of phenol was
      effectively implemented at 160 degrees C using Cu-promoted catalyst (Ce15Cu5).
      Furthermore, at 180 degrees C this catalyst produced about 100% conversion of
      phenol (1h) and 95% removal of chemical oxygen demand (4h), higher than that of
      CeO(2)/gamma-Al(2)O(3). In contrast, Mn-promoted catalyst (Ce15Mn5) required a
      temperature above 220 degrees C for acceptable performance. Activity of re-used
      catalyst declined noticeably, due to deposits of carbonaceous compounds and
      leaching of metal ions. Regeneration with acetone rinsing after the first run was
      effective in recovering activity of Ce15Cu5, although after a second run further
      regeneration with acetone rinsing had only a moderate effect, due to residual
      carbonaceous deposits and the additive effect of leached metal species in each
      run. As an alternative to acetone, HCl or HNO(3) solution (0.01 M) was less
      effective at regenerating activity. In promoted catalysts, leached metal ions
      accounted for the majority of mineralization of phenol, while the solid catalyst
      played a dual role of initiator and terminator of free radicals. Despite a
      superior catalytic performance, leaching of Cu(2+) from the promoted catalyst
      caused a severe decline in activity and poses the problem of secondary pollution
      of treated wastewater. Therefore, addition of Cu, as well as other metal species,
      is unfavorable in promoting the CeO(2)/gamma-Al(2)O(3) catalyst.

PMID- 16806399
TI  - Study of metabolites from the degradation of polycyclic aromatic hydrocarbons
      (PAHs) by bacterial consortium enriched from mangrove sediments.
AB  - The PAH metabolites produced during degradation of fluorene, phenanthrene and
      pyrene by a bacterial consortium enriched from mangrove sediments were analyzed
      using the on-fiber silylation solid-phase microextraction (SPME) combining with
      gas chromatography-mass spectrometry (GC-MS) method. Seventeen metabolites at
      trace levels were identified in different PAH degradation cultures based on the
      full scan mass spectra. In fluorene degradation cultures, 1-, 2-, 3- and 9
      hydroxyfluorene, fluorenone, and phthalic acid were detected. In phenanthrene and
      pyrene degradation cultures, various common metabolites such as phenanthrene and
      pyrene dihydrodiols, mono-hydroxy phenanthrene, dihydroxy pyrene, lactone and 4
      hydroxyphenanthrene, methyl ester, and phthalic acid were found. The detection of
      various common and novel metabolites demonstrates that SPME combining with GC-MS
      is a quick and convenient method for identification as well as monitoring the
      real time changes of metabolite concentrations throughout the degradation
      processes. The knowledge of PAH metabolic pathways and kinetics within indigenous
      bacterial consortium enriched from mangrove sediments contributes to enhance the
      bioremediation efficiency of PAH in real environment.

PMID- 16806400
TI  - Removal of added nitrate in cotton burr compost, mulch compost, and peat:
      mechanisms and potential use for groundwater nitrate remediation.
AB  - We conducted batch tests on the nature of removal of added nitrate in cotton burr
      compost, mulch compost, and sphagnum peat that may be potentially used in a
      permeable reactive barrier (PRB) for groundwater nitrate remediation. A rigorous
      steam autoclaving protocol (121 degrees C for 2h each day for three consecutive
      days) for the cotton burr compost and autoclaving of all labware and the nitrate
      working solutions resulted in drastically different results compared to the non
      autoclaved treatment. In the non-autoclaved cotton burr compost, added nitrate at
      20 mg N l(-1) decreased rapidly and was not detected after 3d; whereas, the
      autoclaved cotton burr compost showed persistent nitrate above 15.5 mg N l(-1)
      even after 10d, which is comparable with nitrate concentrations above 17.6 mg N
      l(-1) in a treatment using NaN(3) at 1000 mg l(-1). Dewaxed cotton burr compost
      showed decreased nitrate reduction compared to the pristine cotton burr compost.
      No nitrate reduction was detected in the dewaxed sphagnum peat. It is concluded
      that nitrate removal in the organic media is controlled by microbiologically
      mediated processes. The use of readily available cotton burr and mulch composts
      may offer a cost-effective method of nitrate removal from contaminated
      groundwater.

PMID- 16806401
TI  - Levels of metals, PCBs, PCNs and PAHs in soils of a highly industrialized
      chemical/petrochemical area: temporal trend.
AB  - In 2005, the concentrations of various metals and organic pollutants were
      analyzed in soils collected in different areas of Tarragona (Catalonia, Spain),
      where an important chemical/petrochemical complex is located. The levels of seven
      elements (As, Cd, Cr, Hg, Mn, Pb and V), as well as those of polychlorinated
      biphenyls (PCBs), polychlorinated naphthalenes (PCNs) and polycyclic aromatic
      hydrocarbons (PAHs) were determined in soils, and compared with those obtained in
      a background study carried out in 2002. Only Cd and Pb showed significant higher
      concentrations in the petrochemical zone, while no significant differences were
      found for the remaining elements. In turn, vanadium was the only element showing
      a significant increase in the concentration between 2002 and 2005. With regard to
      the organic pollutants, no significant differences were found according to the
      area of sampling. However, an increase in naphthalene levels was observed during
      the period 2002-2005 in soils of the chemical and petrochemical areas. According
      to the present results, it is suggested that the levels of vanadium must be
      periodically monitored to assure that the important industrialization of
      Tarragona does not mean health risks for the population living near the complex.

PMID- 16806402
TI  - Dietary intake of dioxins and dioxin-like PCBs, due to the consumption of dairy
      products, fish/seafood and meat from Ismailia city, Egypt.
AB  - Although dietary intake studies have been carried out extensively in most
      developed countries, to evaluate the health risks of PCDD/Fs and DL-PCBs, no data
      of this kind exists for Egypt. In this study, concentrations of PCDD/Fs and DL
      PCBs were measured using HRGC/HRMS in the most contributing foodstuffs (dairy
      products, fish/seafood, and meat) randomly collected from Ismailia city, Egypt.
      The dietary intake of PCDD/Fs and DL-PCBs were subsequently determined, and
      compared with the most recent studies. To provide a primary estimation of the
      whole TEQ intake in Egypt if all the main food categories included, an estimation
      of the dietary intake (based on EU data) for some important and non-measured
      groups (cereals, vegetables/fruits, eggs and milk) was carried out. The
      calculated dietary intake based on the WHO assumption of 60 kg bw ranged from
      3.69 to 4.0 pg WHO-TEQ/kg bw/day for PCDD/Fs and from, 6.04 to 6.68 pg WHO-TEQ/kg
      bw/day, if DL-PCBs were included. PCBs intake contributed about 40% of the total
      TEQ intake. Dairy products (mainly cheese) were the main contributor to the
      intake of PCDD/Fs (89%), while fish/seafood and meat have more or less the same
      percent share (5.4%). The dairy products contamination was the reason for our
      elevated dietary intake, as the content of PCDD/Fs and DL-PCBs is several times
      higher than in all the developed countries. The total intake (PCDD/Fs+DL-PCBs)
      due to consumption of dairy products, fish/seafood and meat, is close to that
      reported in EU countries at the beginning of 1980s, but much higher than all
      those mentioned in all the recent reports, and higher than the maximum WHO TDI of
      4 pg TEQ/kg bw/day. A recalculation of the dietary intake to include not only our
      measured data but also the data for the non-measured groups, yielded a total
      intake in the range of 4.06-6.38 pg TEQ/kg bw/day for PCDD/Fs and a range of 6.59
      9.98 pg TEQ/kg bw/day for total including PCBs. Results show that cereals and
      vegetables/fruits contribute significantly to PCDD/Fs TEQ intake in Egypt and
      play a more important role than fish/seafood and meat. This is the case even
      though the intake for cereals and vegetables/fruits based on EU data.

PMID- 16806404
TI  - Nature and extent of the exposure to fibrous amphiboles in Biancavilla.
AB  - An epidemiological and environmental study in the Biancavilla area (Sicily,
      Italy) was recently prompted by an impressively high incidence of malignant
      pleural mesothelioma. Epidemiology suggested an environmental contamination by
      amphibole fibres rather than risks related to a specific occupational activity.
      The aim of this study is to describe the diffusion of fibrous amphiboles in the
      area and identify their source. Fibrous amphiboles were found in the products
      from the local quarries, which had been used for years to build houses. After
      sampling all around Biancavilla, three sites were detected and they were
      characterized by an abundant presence of mineral fibres. Fibrous amphiboles were
      also recovered from building materials (mortar and plasters) and airborne
      particulates sampled in urban sites with high dust emissions due mainly to
      unpaved roads. Moreover, amphibole fibres were detected in the lung tissue of a
      woman who died of pleural mesothelioma. The results of this study suggest that
      the amphibole fibre diffusion in the Biancavilla environment lasted for many
      years and had been maximum during the sixties and the seventies with the
      uncontrolled development of the local building industry. Today, the environmental
      situation results to be changed following both the closing of the stone quarries
      and the urbanization works after 2001, above all the asphalting of dusty roads.
      Anyway sporadic mesothelioma cases have still to be expected in the next years.

PMID- 16806403
TI  - The role of the sea-surface microlayer in the air-sea gas exchange of
      organochlorine compounds.
AB  - Simultaneous measurements of organochlorine compounds (OCs) in seawater, the sea
      surface microlayer and the atmosphere were conducted in June-July 2004 in the
      coastal marine environment of Singapore. Together, these measurements represent
      the first data on the flux of OCs between the ocean and atmosphere reported in
      the scientific literature that take into account the implication of the sea
      surface microlayer (SML) as a controlling boundary layer for the exchange of OCs.
      The average fluxes of SigmaPCBs and SigmaHCHs were 127.5 and -32.8 ng m(-2) day(
      1) respectively using a modified two-layer model (negative flux indicates
      adsorption by the ocean). The average fluxes using a conventional approach,
      ignoring the SML as boundary layer (classical two-layer model), were 67.2 and 
      43.1 ng m(-2) day(-1) for SigmaPCBs and SigmaHCHs, respectively. However, the
      maximum difference in the flux calculation between the two approaches was up to
      15-fold for individual compounds at high enrichment in the SML. It is shown that
      the SML plays an important role in the control of air-sea gas exchange of OCs,
      particular under a low prevailing wind regime and with an enrichment of OCs in
      the SML. The physical and chemical properties of OCs are critical factors in the
      control of the air-sea gas exchange process, and the effect of the SML on this
      process is more significant for more hydrophobic OCs.

PMID- 16806405
TI  - A review of acidity generation and consumption in acidic coal mine lakes and
      their watersheds.
AB  - Lakes developing in former coal mine pits are often characterized by high
      concentrations of sulfate and iron and low pH. The review focuses on the causes
      for and fate of acidity in these lakes and their watersheds. Acidification is
      primarily caused by the generation of ferrous iron bearing and mineralized
      groundwater, transport through the groundwater-surface water interface, and
      subsequent iron oxidation and precipitation. Rates of acidity generation in mine
      tailings and dumps, and surface water are often similar (1 to >10 mol m(-2) yr(
      1)). Weathering processes, however, often suffice to buffer groundwaters to only
      moderately acidic or neutral pH, depending on the suite of minerals present. In
      mine lakes, the acidity balance is further influenced by proton release from
      transformation of metastable iron hydroxysulfate minerals to goethite, and proton
      and ferrous iron sequestration by burial of iron sulfides and carbonates in
      sediments. These processes mostly cannot compensate acidity loading from the
      watershed, though. A master variable for almost all processes is the pH: rates of
      pyrite oxidation, ferrous iron oxidation, mineral dissolution, iron
      precipitation, iron hydroxide transformation, and iron and sulfate reduction are
      strongly pH dependent. While the principle mechanism of acidity generation and
      consumption and several controls are mostly understood, this cannot be said about
      the fate of acidity on larger spatial and temporal scales. Little is also known
      about critical loads and the internal regulation of biogeochemical iron, sulfur,
      and carbon cycling in acidic mine lakes.

PMID- 16806406
TI  - Quantifying submarine groundwater discharge in the coastal zone via multiple
      methods.
AB  - Submarine groundwater discharge (SGD) is now recognized as an important pathway
      between land and sea. As such, this flow may contribute to the biogeochemical and
      other marine budgets of near-shore waters. These discharges typically display
      significant spatial and temporal variability making assessments difficult.
      Groundwater seepage is patchy, diffuse, temporally variable, and may involve
      multiple aquifers. Thus, the measurement of its magnitude and associated chemical
      fluxes is a challenging enterprise. A joint project of UNESCO and the
      International Atomic Energy Agency (IAEA) has examined several methods of SGD
      assessment and carried out a series of five intercomparison experiments in
      different hydrogeologic environments (coastal plain, karst, glacial till,
      fractured crystalline rock, and volcanic terrains). This report reviews the
      scientific and management significance of SGD, measurement approaches, and the
      results of the intercomparison experiments. We conclude that while the process is
      essentially ubiquitous in coastal areas, the assessment of its magnitude at any
      one location is subject to enough variability that measurements should be made by
      a variety of techniques and over large enough spatial and temporal scales to
      capture the majority of these changing conditions. We feel that all the
      measurement techniques described here are valid although they each have their own
      advantages and disadvantages. It is recommended that multiple approaches be
      applied whenever possible. In addition, a continuing effort is required in order
      to capture long-period tidal fluctuations, storm effects, and seasonal
      variations.

PMID- 16806407
TI  - Fine root biomass, necromass and chemistry during seven years of elevated
      aluminium concentrations in the soil solution of a middle-aged Picea abies stand.
AB  - Toxic effects of aluminium (Al) on Picea abies (L.) Karst. (Norway spruce) trees
      are well documented in laboratory-scale experiments, but field-based evidence is
      scarce. This paper presents results on fine root growth and chemistry from a
      field manipulation experiment in a P. abies stand that was 45 years old when the
      experiment started in 1996. Different amounts of dissolved aluminium were added
      as AlCl3 by means of periodic irrigation during the growing season in the period
      1997-2002. Potentially toxic concentrations of Al in the soil solution were
      obtained. Fine roots were studied from direct cores (1996) and sequential root
      ingrowth cores (1999, 2001, 2002) in the mineral soil (0-40 cm). We tested two
      hypotheses: (1) elevated concentration of Al in the root zone leads to
      significant changes in root biomass, partitioning into fine, coarse, living or
      dead fractions, and distribution with depth; (2) elevated Al concentration leads
      to a noticeable uptake of Al and reduced uptake of Ca and Mg; this results in Ca
      and Mg depletion in roots. Hypothesis 1 was only marginally supported, as just a
      few significant treatment effects on biomass were found. Hypothesis 2 was
      supported in part; Al addition led to increased root concentrations of Al in 1999
      and 2002 and reduced Mg/Al in 1999. Comparison of roots from subsequent root
      samplings showed a decrease in Al and S over time. The results illustrated that 7
      years of elevated Al(tot) concentrations in the soil solution up to 200 microM
      are not likely to affect root growth. We also discuss possible improvements of
      the experimental approach.

PMID- 16806408
TI  - Decreased nitric oxide and increased platelet aggregation levels in patients with
      Behcet's disease.

PMID- 16806409
TI  - Delayed thrombin-induced platelet-fibrin clot generation by clopidogrel: a new
      dose-related effect demonstrated by thrombelastography in patients undergoing
      coronary artery stenting.
AB  - BACKGROUND: We have previously demonstrated that clopidogrel reduces platelet
      activation and aggregation in patients undergoing stenting. However, the effect
      of the clopidogrel loading dose on the rate of thrombin-induced platelet-fibrin
      clot formation is unknown in this patient population. METHODS AND RESULTS: Using
      thrombelastography (TEG) we measured the time to platelet-fibrin clot formation
      (R), a marker of the speed of thrombin generation, in 120 patients undergoing
      elective coronary artery stenting treated with standard and high loading doses of
      clopidogrel. Platelet reactivity to adenosine diphosphate (ADP) by light
      transmittance aggregometry (LTA) was determined simultaneously. Measurements were
      made immediately before and at 24 h after clopidogrel treatment. Clopidogrel
      produced a prolongation in R (4.4+/-1.4 min pre vs. 5.4+/-1.7 min post, p<0.001)
      that directly correlated with the change in platelet aggregation (r=0.65,
      p<0.0001). Prolongation in R was greatest in patients treated with a high loading
      dose (p=0.004). CONCLUSIONS: Delayed thrombin-induced platelet-fibrin clot
      formation as measured by TEG is a newly reported dose-related effect of
      clopidogrel that may contribute to the overall antithrombotic properties of the
      drug in patients undergoing stenting. This effect was more marked in patients
      loaded with 600 mg, lending further mechanistic support for this dose of
      clopidogrel as a more effective antithrombotic regimen than the standard 300 mg
      dose. Measurement of R may serve as a new indicator of clopidogrel
      responsiveness.

PMID- 16806410
TI  - Lymphovascular invasion in radical prostatectomy specimens: prediction of adverse
      pathologic features and biochemical progression.
AB  - OBJECTIVES: Patients and referring physicians often ask about the significance of
      lymphovascular invasion (LVI) on pathology reports from radical prostatectomy
      specimens. However, limited data are available concerning the relationship
      between LVI and preoperative screening characteristics, pathologic tumor
      features, and patient prognosis. METHODS: LVI was evaluated for its ability to
      predict elevated prostate-specific antigen velocity, adverse pathologic features,
      and biochemical progression in 1709 men who underwent radical prostatectomy for
      clinically localized disease. RESULTS: LVI was present in 118 (7%) of the 1709
      men. On univariate analysis, LVI was significantly associated with tumor grade,
      tumor volume, and other adverse pathologic features. Prostate-specific antigen
      velocity was not significantly associated with the presence of LVI. Biochemical
      progression occurred in 34% of those with LVI compared with 10% of those without
      LVI (P <0.0001). However, on multivariate analysis with other pathologic tumor
      features, LVI was not an independent predictor of progression. CONCLUSIONS: LVI
      is a relatively uncommon finding in radical prostatectomy specimens for
      clinically localized disease. Although LVI was seen primarily in large-volume,
      high-grade tumors, it was not an independent predictor of progression in the
      multivariate model.

PMID- 16806411
TI  - No-scalpel, no-needle vasectomy.

PMID- 16806412
TI  - T1c prostate cancer detection rate and pathologic characteristics: comparison
      between patients with serum prostate-specific antigen range of 3.0 to 4.0 ng/mL
      and 4.1 to 10.0 ng/mL in Korean population.
AB  - OBJECTIVES: To prospectively evaluate the Stage T1c prostate cancer detection
      rate and pathologic characteristics of patients with a serum prostate-specific
      antigen (PSA) level of 3.0 to 4.0 ng/mL and compare this with the rate of
      patients who had a PSA level of 4.1 to 10.0 ng/mL. METHODS: We analyzed the data
      of patients who had PSA levels of 3.0 to 10.0 ng/mL, benign findings on digital
      rectal examination, and no specific lesion identified on transrectal
      ultrasonography. The clinical characteristics, cancer detection rate, and
      pathologic findings of the biopsy and prostatectomy specimen were compared
      between the low (3.0 to 4.0 ng/mL) and intermediate (4.1 to 10.0 ng/mL) PSA
      groups. RESULTS: A total of 450 patients met our criteria. Of these 450 patients,
      85 and 365 had a low or an intermediate PSA level, respectively. Prostate cancer
      was diagnosed in 26% of the low and 19% of the intermediate PSA group. No
      significant difference was found between the two groups in the pathologic biopsy
      findings, including the mean Gleason score and percentage of patients with a
      Gleason score of 7 or more. The pathologic findings of the prostatectomy
      specimens also showed no significant differences between the two groups,
      including the mean Gleason score, pathologic stage, and percentage of
      insignificant prostate cancer. CONCLUSIONS: No statistically significant
      difference was found in the incidence of Stage T1c prostate cancer or pathologic
      characteristics in comparison between the low and intermediate PSA groups. These
      results suggest that a lower PSA cutoff should be considered as an indication for
      prostate biopsy in the Korean population.

PMID- 16806413
TI  - Complete urinary tract extirpation: the University of Maryland experience.
AB  - OBJECTIVES: Complete urinary tract extirpation (CUTE) involves simultaneous
      bilateral nephroureterectomy, cystectomy or cystoprostatectomy, and the creation
      of a urinary diversion, if needed. Case reports of this operation have been
      published, but to our knowledge, this is the largest case series yet reported. We
      sought to evaluate the characteristics and outcomes of patients who underwent
      CUTE. METHODS: From 1994 to 2005, 9 patients underwent CUTE at our institution.
      We performed a retrospective chart review of these patients. The data reviewed
      included demographics, operative time, length of stay, complications,
      recurrences, and overall survival. RESULTS: Nine patients who underwent CUTE were
      identified. The mean patient age at the operation was 61 years. Five patients
      were men. The mean operative time was 356 minutes. Two patients required a blood
      transfusion. The length of stay averaged 10.8 days (range 6 to 47). Four patients
      had functioning renal allografts before and after surgery. Three patients needing
      dialysis received renal allografts postoperatively. The overall survival rate at
      a mean follow-up of 31 months was 86%. CONCLUSIONS: Although this report
      presented a small number of patients, it has illustrated that CUTE can be
      performed safely and allow definitive surgical treatment of patients with complex
      genitourinary pathologic findings.

PMID- 16806414
TI  - Complications after radical cystectomy: analysis of population-based data.
AB  - OBJECTIVES: To determine the morbidity and mortality from radical cystectomy in a
      nationally representative population-derived sample. Complications after radical
      cystectomy have been reported from large single-institution series but population
      based representative data are lacking. METHODS: All patients undergoing radical
      cystectomy for bladder cancer were identified from the National Inpatient Sample
      data set of the Health Care Utilization Project (1998 to 2002). The prevalence of
      different complications coded according to the International Classification of
      Diseases, version 9, after cystectomy were determined. Independent hospital and
      patient-related factors associated with the occurrence of a complication were
      determined by logistic regression analysis. The prevalence of complication by
      type and frequency were compared with that in other large reported series.
      RESULTS: The in-hospital mortality rate was 2.57%, and at least one complication
      other than death occurred in 28.4% of patients. These rates were comparable to
      those reported in published studies. Younger patients had a lower likelihood of
      complications. Younger patients and those undergoing cystectomy at large bed
      size, urban, teaching hospitals were less likely to have secondary complications
      after surgery, and younger patients, women, and those undergoing cystectomy at
      high-volume hospitals were less likely to have primary complications directly
      related to their surgery. CONCLUSIONS: The overall morbidity and mortality rates
      after radical cystectomy in a population-based sample were comparable to those
      reported from individual centers. Larger centers in urban locations may have
      lower complication rates but only hospitals performing a high volume of
      cystectomies were associated with fewer primary surgery-related complications.

PMID- 16806415
TI  - Adjuvant systemic chemotherapy in the treatment of patients with invasive
      transitional cell carcinoma of the upper urinary tract.
AB  - OBJECTIVES: To evaluate the efficacy of adjuvant systemic chemotherapy in
      conjunction with surgery in patients with invasive transitional cell carcinoma of
      the upper urinary tract. METHODS: From January 1991 to May 2001, 36 men and 7
      women had invasive (Stage pT2 or worse), but not metastatic, disease and were the
      subjects of this study. Their median age was 59 years (range 36 to 72). Of these
      43 patients, 32 were scheduled to receive more than four courses of cisplatin
      based chemotherapy. The median follow-up period of all the evaluated patients was
      30.7 months (range 4.7 to 98.8). RESULTS: Recurrence was observed in 12 patients
      (37.5%) who underwent chemotherapy and 7 (63.6%) who did not (P = 0.170). The
      disease-free survival was lower in the nonchemotherapy group than in the
      chemotherapy group (P = 0.0439). During the follow-up period, 9 patients (28.1%)
      in the chemotherapy group died and 9 patients (81.8%) in the nonchemotherapy
      group died (P = 0.004). Multivariate Cox proportional hazard model analysis
      revealed that the use of adjuvant chemotherapy (P = 0.006, relative risk = 9.19)
      and node-positive status (P = 0.008, relative risk = 8.28) were strongly
      associated with overall survival. In the chemotherapy group, 24 (75%) had side
      effects due to the treatment; however, fever and gastrointestinal symptoms were
      the chief adverse effects and were well tolerated. CONCLUSIONS: Our results have
      indicated that adjuvant systemic chemotherapy may provide therapeutic benefit in
      patients with invasive transitional cell carcinoma of the upper urinary tract.

PMID- 16806416
TI  - Examination of laparoscopic retrieval bag washings for malignant cells after hand
      assisted laparoscopic radical nephrectomy and intact specimen removal.
AB  - OBJECTIVES: Port site metastases after hand-assisted laparoscopic radical
      nephrectomy have been described in the literature. There is no uniform agreement
      among urologists regarding the use of a retrieval bag before intact specimen
      removal. The aim of this study was to determine whether LapSac renal extraction
      bag washings contain malignant cells. METHODS: We prospectively obtained washings
      from the LapSac retrieval bag after hand-assisted laparoscopic radical
      nephrectomy and intact specimen removal for renal cell carcinoma. In 30
      consecutive cases, after removal of the kidney specimen from the LapSac, the
      LapSac was irrigated with 50 mL sterile Hank's balanced salt solution. These
      washings were sent for cytologic examination. Cytologic evaluation was performed
      with a Thin Prep and the Papanicolaou method. RESULTS: We performed 30 hand
      assisted laparoscopic radical nephrectomies for suspected renal cell carcinoma
      with the above protocol. One specimen was benign and one showed transitional cell
      carcinoma; these were excluded from the study. Six specimens were stage T1a, 17
      were T1b, 1 was T2, 2 were T3a, and 2 were T3b. Histopathology revealed 27
      specimens with clear cell renal cell carcinomas with Fuhrman grades from 1 to 4;
      1 specimen showed chromophobe renal cell carcinoma. Margins were negative in all
      cases, and there were no gross or microscopic tumor violations. The cytologic
      results from 27 cases were negative and in 1 case with T3b renal cell carcinoma
      the LapSac washings were positive for malignant cells. CONCLUSIONS: The
      preliminary findings from our study show that low-stage, low-grade tumors removed
      laparoscopically with minimal manipulation do not exfoliate cells into their
      LapSac retrieval bags.

PMID- 16806417
TI  - Hand-assisted laparoscopic ureterolysis to treat ureteral obstruction secondary
      to idiopathic retroperitoneal fibrosis: assessment of a novel technique and
      initial series.
AB  - OBJECTIVES: To describe a novel technique and assess an initial series of hand
      assisted laparoscopic ureterolysis for the treatment of retroperitoneal fibrosis.
      METHODS: Five patients (3 women and 2 men, mean age 56.4 years) with ureteral
      obstruction secondary to retroperitoneal fibrosis underwent bilateral hand
      assisted laparoscopic ureterolysis with biopsy. These patients had undergone an
      imaging evaluation with excretory urography, computed tomography, furosemide
      washout nucleotide scan, and/or magnetic resonance imaging. All had ureteral
      stents placed before or at surgery. A periumbilical hand port, bilateral 10-mm
      perirectal camera ports, and bilateral 5-mm or 10-mm working ports were placed.
      The ureters were completely mobilized and placed intraperitoneally. The patient
      demographic, operative, and early and late postoperative data were collected.
      RESULTS: The average operating room time was 259 minutes (range 215 to 300), and
      the estimated blood loss was 80 mL (range 50 to 200). The mean hospital stay was
      4.20 days (range 3 to 5). One minor intraoperative ureteral injury and no
      postoperative complications occurred. The mean analgesic requirement was 45.6 mg
      morphine sulfate (range 20 to 88). Three patients also received 120 mg of
      parenteral ketorolac. All indwelling ureteral stents were removed by 2 to 4 weeks
      postoperatively. At 22.4 months (range 12 to 29) postoperatively, 90% of the
      renal units were unobstructed. CONCLUSIONS: Hand-assisted laparoscopic
      ureterolysis is an effective minimally invasive technique with less morbidity
      than open ureterolysis. It offers a shorter operative time and is less
      technically challenging than conventional laparoscopy. It is our preferred
      surgical approach for obstructive retroperitoneal fibrosis.

PMID- 16806418
TI  - Percutaneous suprapubic cystolithotripsy under local anesthesia.
AB  - OBJECTIVES: To assessed the feasibility and effectiveness of percutaneous
      cystolithotripsy under local anesthesia in selected patients. METHODS: Thirty-one
      patients with bladder stones of different etiologies underwent percutaneous
      cystolithotripsy under local anesthesia. Suprapubic access was obtained with
      ultrasound guidance, and fragmentation of the stone was performed using the Swiss
      lithoclast. Suprapubic and transurethral catheters were placed postoperatively.
      RESULTS: No major intraoperative complications occurred. The whole procedure was
      well tolerated, and no significant differences were found in the mean pain score
      between the percutaneous suprapubic cystolithotripsy group and a group of male
      patients who underwent rigid cystoscopy under local anesthesia (P = 0.35).
      Complete stone clearance was achieved in all but 1 patient (96.78%). Bladder
      irrigation because of gross hematuria was needed in 5 patients, but no blood
      transfusion was required. Fever developed in 1 patient and was treated with
      intravenous antibiotics. The average hospitalization was 2.3 days (range 2 to 5).
      After a mean follow-up of 10 months, no recurrent stone developed. CONCLUSIONS:
      Percutaneous suprapubic cystolithotripsy under local anesthesia is a safe and
      effective technique to remove bladder calculi. Thus, it may be used as an
      alternative treatment option in selected patients.

PMID- 16806419
TI  - Role of volume and attenuation value histogram of urinary stone on noncontrast
      helical computed tomography as predictor of fragility by extracorporeal shock
      wave lithotripsy.
AB  - OBJECTIVES: To test, for the first time, the predictive capability of the total
      stone volume (TSV) and the attenuation value histogram. Recently, the mean
      attenuation value (MAV) of urinary stones has been recognized as a predictor of
      fragility by extracorporeal shock wave lithotripsy. However, properties other
      than MAV, including the TSV and the heterogeneity of attenuation value histogram,
      may also be related to fragility. METHODS: A total of 62 renal and proximal
      ureteral radiopaque stones treated with extracorporeal shock wave lithotripsy
      were included in this prospective study. Stones less than 5 mm or greater than 20
      mm were excluded. Attenuation value histograms were graphed from the data from
      noncontrast helical computed tomography scans. The TSV, MAV, and hump existence
      (HE) on the histogram were also calculated. These parameters were compared
      between the treatment success and treatment failure groups. RESULTS: Of the 62
      stones, 6 were excluded, 39 were in the success group, and 17 in the failure
      group. Of the 56 stones, 16 had a hump and 40 did not on the attenuation value
      histograms. The TSV, MAV, and HE were significantly different statistically
      between the two groups (P <0.001), with an accuracy of 82.1%, 83.9%, and 91.1%,
      respectively. Also, HE was the only independent predictor of success or failure
      of extracorporeal shock wave lithotripsy on multivariate analysis (P = 0.0073).
      CONCLUSIONS: Our results have suggested that TSV, MAV, and HE are good predictors
      of stone fragility. The treatment modality of the stone should be selected
      according to the HE, which is a practical, simple, and predictive index.

PMID- 16806420
TI  - Can prilocaine infiltration alone be the most minimally invasive approach in
      terms of anesthesia during extracorporeal shock wave lithotripsy?
AB  - OBJECTIVES: To evaluate the analgesic effect and utility of prilocaine
      infiltration alone for minimal morbidity during extracorporeal shock wave
      lithotripsy. METHODS: A total of 114 patients with kidney stones, aged 18 to 69
      years, were randomly separated into two groups. The 58 patients in group 1
      received intramuscular diclophenac 30 minutes before extracorporeal shock wave
      lithotripsy, and the 56 patients in group 2 received prilocaine infiltration into
      the 30 cm2 area below the 12th rib right before the session. A visual analog
      scale (0 to 100 mm) was used to evaluate pain. RESULTS: The visual analog scale
      scores for group 2 were statistically lower at 1, 10, and 20 minutes compared
      with the scores for group 1 (P = 0.006, P = 0.005, and P = 0.006, respectively).
      However, no difference was detected at the end of the procedure. The requirement
      for additional analgesic was less in group 2 (P = 0.007). CONCLUSIONS: Prilocaine
      infiltration alone can be used for analgesic purposes efficiently and safely
      during extracorporeal shock wave lithotripsy with minimal morbidity.

PMID- 16806421
TI  - IkappaB kinase 2 inhibition corrects defective nitrergic erectile mechanisms in
      diabetic mouse corpus cavernosum.
AB  - OBJECTIVES: Oxidative or glyco-oxidative stress-induced activation of the
      transcription factor, nuclear factor (NF)-kappaB, is associated with the
      neurovascular complications of diabetes mellitus. Antioxidant treatment has
      beneficial effects in diabetic patients; however, delineating a possible role for
      NF-kappaB deactivation against direct antioxidant effects has been difficult. NF
      kappaB is negatively regulated by the inhibitor of kappaB (IkappaB) complex that,
      in turn, is activated by specific kinases. Thus, the aim was to investigate the
      effects of the IkappaB kinase 2 inhibitor, AS602868, on corpus cavernosum
      function in diabetic mice. METHODS: Diabetes was induced by streptozotocin; the
      duration was 6 weeks. Intervention AS602868 treatment (100 mg/kg/day) was given
      for 2 weeks after 4 weeks of untreated diabetes. Corpora cavernosum were isolated
      in organ baths for measurement of agonist-evoked or electrical stimulation-evoked
      smooth muscle tensions. RESULTS: The maximal nitrergic nerve-mediated relaxation
      of phenylephrine-precontracted cavernosum was reduced approximately 30% by
      diabetes (P <0.001). AS602868 treatment completely reversed the deficit (P
      <0.001). Maximal nitric oxide-mediated endothelium-dependent relaxation to
      acetylcholine was attenuated approximately 32% by diabetes (P <0.05). This was
      completely restored by IkappaB kinase 2 inhibition (P <0.01). Furthermore,
      AS602868 treatment also completely corrected (P <0.01) an approximate 20%
      diabetic deficit (P <0.001) in maximal endothelium-independent relaxation to the
      nitric oxide donor, sodium nitroprusside. CONCLUSIONS: Inhibition of IkappaB
      kinase 2 can correct nitric oxide-dependent indexes of diabetic erectile
      dysfunction. This suggests that NF-kappaB activation is important in the
      development of diabetic cavernosum nitrergic neuropathy and vasculopathy.

PMID- 16806422
TI  - Immunohistochemical expression of tumor antigens MAGE-A1, MAGE-A3/4, and NY-ESO-1
      in squamous cell carcinoma of the penis.
AB  - OBJECTIVES: To investigate by immunohistochemistry the expression of MAGE-A and
      NY-ESO-1/LAGE-1, cancer testis antigens (CTAs), in squamous cell carcinoma of the
      penis. METHODS: A total of 30 penile carcinoma samples from patients undergoing
      penile amputation at the Urology Clinics at the Zagreb Clinical Hospital Center
      and University Hospital "Sestre milosrdnice" from 1997 to 2004 were investigated
      in this study. Three monoclonal antibodies were used for immunohistochemical
      staining: 77B specific for MAGE-A1, 57B recognizing multiple MAGE-A CTAs, and
      D8.38, specific for NY-ESO-1 antigen. RESULTS: The expression of MAGE-A1 was not
      observed in the carcinoma samples, but both multi-MAGE-A and NY-ESO-1-specific
      reagents stained 29 (97%) of 30 samples. Immunohistochemical staining was
      prevailingly detected in the cytoplasm. A significant heterogeneity was observed
      within the same specimen, in which areas with strong positivity coexisted with
      CTA-negative areas. The extent of CTA expression did not correlate significantly
      with tumor grade. CONCLUSIONS: The results of this study have documented for the
      first time the expression of CTAs in squamous cell carcinoma of the penis.
      Additional research is warranted to explore the potential implications regarding
      both diagnosis and therapy.

PMID- 16806423
TI  - Meconium periorchitis.

PMID- 16806424
TI  - Anterior transanal, transsphincteric sagittal approach for fistula repair
      secondary to laparoscopic radical prostatectomy: a simple and effective
      technique.
AB  - INTRODUCTION: To report our experience with the anterior, transanal,
      transsphincteric, sagittal approach in the correction of rectourinary fistula
      secondary to laparoscopic radical prostatectomy. TECHNICAL CONSIDERATIONS: Of the
      first 110 laparoscopic extraperitoneal radical prostatectomies performed from
      December 2001 to February 2004, 9 (8%) were complicated by rectal injury. Of the
      nine rectal lesions, seven were diagnosed intraoperatively and the rectal defects
      closed laparoscopically. Primary repair failed in 1 of the 7 patients. In 2 other
      patients, the rectal injuries were missed intraoperatively, and a rectourinary
      fistula later developed. Rectourinary fistula was confirmed in these 3 patients
      by cystoscopy and digital rectal examination. The procedure chosen for repair was
      the anterior sagittal transrectal anal approach. The time from diagnosis to
      fistula repair was 1 to 3 months. Fistula repair was successful in all patients.
      The mean follow-up was 12 to 24 months. No patient presented with fecal
      incontinence or anal strictures. Postprostatectomy urinary continence was not
      affected by the procedure. CONCLUSIONS: The transsphincteric transanal surgical
      approach provides many advantages for the repair of acquired urethrorectal
      fistulas after laparoscopic radical prostatectomy. It allows for good surgical
      exposure and fistula tract identification and ensures good access to well
      vascularized tissue. This surgical technique is simple, effective, reproducible,
      and associated with minimal morbidity.

PMID- 16806425
TI  - Laparoscopic-assisted radical cystectomy with U-shaped orthotopic ileal
      neobladder constructed using nonabsorbable titanium staples.
AB  - INTRODUCTION: Recently, nonabsorbable staples have been safely used in a variety
      of urologic open and laparoscopic extirpative and reconstructive procedures. We
      report the surgical steps of our technique of U-shaped orthotopic ileal
      neobladder created with titanium staples. TECHNICAL CONSIDERATIONS: Using stay
      stitches, a 45 to 50-cm ileal segment is arranged in a U shape with two segments
      of approximately 20 cm and an afferent limb of 5 or 10 cm. An opening is made at
      the lowest point of the U-ileal segment on its antimesenteric border. The jaws of
      the 80 x 3.5-mm nonabsorbable mechanical stapler are accommodated within the
      bowel loop and fired twice, bringing together and detubularizing approximately 15
      cm of each arm of the U. To complete the pouch detubularization, another small
      opening is made at the bottom of the chimney on its medial border. After this, a
      third nonabsorbable mechanical stapler had its jaws introduced through this
      opening and through the open end of the bowel segment on the right side and the
      stapler is fired, completing the U pouch. Subsequently, the open ends of the U
      segment and the opening made at the base of the afferent limb are closed with
      absorbable running sutures. CONCLUSIONS: Our technique is feasible and may
      represent an alternative to expand the spectrum of continent urinary reservoirs
      that could be expeditiously created with nonabsorbable staples. Continued
      surveillance is mandatory to determine the lithiasis-inducing potential of these
      titanium staples within the urinary tract.

PMID- 16806426
TI  - Decrease in nocturnal urinary levels of arginine vasopressin in patients with
      nocturnal polyuria.
AB  - OBJECTIVES: To elucidate whether heart function and endocrine levels of arginine
      vasopressin (AVP) or solute diuresis is associated with the nocturnal voided
      volume, and whether the urinary AVP could be a parameter for screening for
      nocturnal polyuria caused by AVP insufficiency. METHODS: A total of 50 patients
      were enrolled in this study. The blood and urine samples were obtained every 6
      hours at 6 pm, 12 am, 6 am, and 12 pm. Atrial natriuretic peptide and brain
      natriuretic peptide were measured at admission. All voided urine samples were
      collected every 6 hours for examination. The evaluation items were AVP,
      osmolarity, sodium, potassium, chloride, and creatinine in blood and urine.
      RESULTS: The patients were classified into a group with nocturnal polyuria (n =
      21) and a group without nocturnal polyuria (n = 25). There was no significant
      difference in atrial natriuretic peptide, brain natriuretic peptide, electrolytes
      in blood and urine, and plasma AVP of each sample between the two groups, but
      urinary AVP/urinary creatinine and urine osmolarity at 12 am and 6 am in the
      group with nocturnal polyuria were significantly lower than those in the group
      without nocturnal polyuria. The nocturnal voided volume correlated with urinary
      AVP/urinary creatinine level in the urine samples obtained at 12 am and 6 am.
      CONCLUSIONS: The present data have demonstrated that the significant decrease in
      urinary AVP/urinary creatinine level at 6 am may contribute to the increased
      nocturnal voided volume followed by nocturia and that the circadian rhythm
      disorder of AVP can be predicted by a noninvasive test measuring urinary
      AVP/urinary creatinine in the urine voided early in the morning.

PMID- 16806427
TI  - Technical refinement for third kidney transplantation.
AB  - To overcome the technical difficulties of a third renal transplantation, we
      developed a refined technique. After native ureteral stenting, the subhepatic
      retroperitoneum was approached by way of a midline incision. The renal vein was
      sewn to the vena cava, the artery to the common iliac artery, and the ureter to
      the native stented ureter.

PMID- 16806428
TI  - Investigation of factors affecting result of distal hypospadias repair:
      comparison of two techniques.
AB  - OBJECTIVES: To evaluate the factors affecting the results, as well as the success
      of two techniques, by retrospectively investigating cases of distal hypospadias
      in which the patients had undergone Mathieu urethroplasty or tubularized incised
      plate urethroplasty. METHODS: We retrospectively evaluated 117 patients who
      underwent distal hypospadias repair. A percutaneous suprapubic catheter
      (Cistofix) and urethral split catheter were placed as a diversion in the 41
      patients undergoing Mathieu urethroplasty. The Cistofix and urethral catheter
      were placed in 35 patients and a urethral catheter was placed in 41 of the
      patients who underwent tubularized incised plate urethroplasty. The success rates
      were compared according to the surgical technique, age, hypospadias status
      (primary or secondary), type of urinary diversion, and presence of chordee.
      RESULTS: No statistically significant difference in the success rate was found
      between the two techniques. Furthermore, the different types of diversion used in
      tubularized incised plate urethroplasty did not affect the success rate. When the
      success of primary hypospadias repair (n = 84) was compared with secondary
      hypospadias repair (n = 33), success in patients with secondary hypospadias was
      low. No difference was observed when operational success was compared in terms of
      patient age (older versus younger than 5 years of age) or the presence or absence
      of chordee. CONCLUSIONS: Our results have shown that tubularized incised plate
      urethroplasty should be preferred for distal hypospadias because of the better
      cosmetic results, invasive urinary diversions should be avoided, and the most
      importance should be given to the initial surgical intervention.

PMID- 16806429
TI  - Holmium: yttrium-aluminum-garnet laser puncture of ureteroceles in neonatal
      period.
AB  - OBJECTIVES: The use of the holmium:yttrium-aluminum-garnet (YAG) laser to incise
      a ureterocele in children has been reported. However, its use to puncture
      ureteroceles in neonates has not. Therefore, we evaluated the effectiveness and
      safety of ureterocele puncture using a holmium-YAG laser in neonatal patients.
      METHODS: We reviewed our experience of all neonates (ie, children younger than 28
      days old) who underwent transurethral puncture of a ureterocele. The preoperative
      data collected included age at presentation, mode of presentation, ureterocele
      location, and weight and age at the procedure. A holmium:YAG laser was used to
      incise the ureterocele, and a 200, 365, or 550-microm laser fiber was passed
      through a 6F or 7.5F cystoscope. RESULTS: A total of 4 neonates (2 boys and 2
      girls) underwent transurethral holmium laser puncture of five ureteroceles. All
      patients were initially diagnosed with prenatal ultrasound findings confirmed
      after birth with additional imaging. The mean age at the initial puncture was
      13.8 days, with a mean patient weight of 3.9 kg. The mean follow-up was 2.8 years
      (range 1.7 to 3.4). Four (80%) of five ureteroceles were adequately decompressed
      after one attempt. One patient required a second puncture of the ureterocele at
      46 days of age because of incomplete decompression. None of the patients
      experienced an intraoperative or postoperative complication, including new
      vesicoureteral reflux after laser puncture. CONCLUSIONS: Holmium:YAG laser
      puncture of ureterocele is a safe, efficacious, and viable option for children in
      the neonatal period. However, this technique in these young children requires
      additional evaluation.

PMID- 16806430
TI  - Management of neonates with large abdominal wall defects and undescended testis.
AB  - OBJECTIVES: To assess, in a retrospective study, the outcome of different
      treatment modalities in newborns with undescended testes secondary to large
      abdominal wall or diaphragmatic defects. Large abdominal and diaphragmatic
      defects are known to be associated with cryptorchidism, yet the reported
      incidence varies widely. METHODS: A total of 112 neonates with large abdominal
      wall or diaphragmatic defects were treated from 1981 to 2005. Of the 55 male
      patients in this series, 9 (16.4%) presented with abdominal testes and 4 had an
      extra-abdominal testis (7.3%). RESULTS: The 2 patients undergoing primary
      orchiopexy had testes of normal size and in the normal position at last follow
      up. In one of these patients in whom the testis was brought down to the internal
      inguinal ring, spontaneous descent occurred and the testis on the affected side
      was normal. The other patient required additional surgery and had an atrophic
      testis at last follow-up. In 1 patient with severe concomitant malformations,
      primary orchiectomy was performed. The 4 patients who did not receive initial
      treatment all lost their testes owing to atrophy. CONCLUSIONS: The results of the
      present study have indicated that primary orchiopexy should be attempted in all
      cases of abdominal wall defects associated with abdominal cryptorchid testes
      because it yields better testicular salvage rates. In cases in which the
      spermatic cord is not long enough to place the testis into the scrotum,
      mobilization and fixation at the lowest site possible resulted in better outcomes
      than leaving the testis in the abdomen.

PMID- 16806431
TI  - Anxiety disorders in children with epispadias-exstrophy.
AB  - OBJECTIVES: To evaluate the hypothesis that anxiety disorders are common comorbid
      conditions in children with the epispadias-exstrophy complex. METHODS: Twenty
      consecutive outpatient exstrophy subjects ranging in age from 5 to 22 years were
      assessed using a formalized semistructured psychiatric evaluation and were
      categorized according to the Diagnostic and Statistical Manual of Mental
      Disorders, version IV, criteria. Disorders were identified if subjects endured
      moderate to severe impairment in their home, academic, and social environments.
      RESULTS: All 20 subjects met the criteria for at least one anxiety disorder; 19
      met criteria for more than one anxiety disorder. The adolescent subjects
      described a gradual waning of some specific symptoms some time after surgical
      correction of the physical conditions (eg, incontinence) but intensifying sexual
      anxiety with age. CONCLUSIONS: The epispadias-exstrophy complex appears to be
      associated with clinically significant vulnerabilities for anxiety disorders in
      children.

PMID- 16806432
TI  - Impact of extent of lymphadenectomy on survival after radical prostatectomy for
      prostate cancer.
AB  - OBJECTIVES: Controversy exists regarding the benefit of extended lymphadenectomy
      at radical prostatectomy for prostate cancer. We sought to determine whether more
      extended lymphadenectomy, along with radical prostatectomy, resulted in a
      decreased risk of prostate cancer-specific death at 10 years. METHODS: Data on
      all patients undergoing radical prostatectomy (with or without lymphadenectomy)
      for prostate cancer obtained from the Surveillance, Epidemiology, and End Results
      Program (1988 to 1991) were examined. All surviving patients had a minimal follow
      up of 10 years. Multivariate Cox proportional hazards analysis was used to
      determine the independent effect of lymphadenectomy on the risk of prostate
      cancer-specific death. RESULTS: Patients undergoing excision of at least 4 lymph
      nodes (node-positive and node-negative patients) or more than 10 nodes (only node
      negative patients) had a lower risk of prostate cancer-specific death at 10 years
      than did those who did not undergo lymphadenectomy. The removal of a greater
      number of nodes was associated with a greater likelihood of the presence of
      positive nodes. The presence of more than one positive node was associated with a
      greater risk of prostate cancer-related death. CONCLUSIONS: Performing more
      extensive pelvic lymphadenectomy in patients undergoing radical prostatectomy
      could improve the accuracy of staging and reduce the risk of prostate cancer
      specific death in the long term.

PMID- 16806433
TI  - Prognostic significance of immunohistochemical expression of the HER-2/neu
      oncoprotein in bone metastatic prostate cancer.
AB  - OBJECTIVES: To investigate the usefulness of the overexpression of the human
      epidermal growth factor receptor (HER-2) oncoprotein in patients with bone
      metastatic prostate cancer as a marker for the time to recurrence and outcome
      after endocrine therapy. METHODS: We studied 50 patients who had been diagnosed
      with bone metastatic prostate cancer. HER-2 overexpression in the prostatic
      tissue by biopsy was evaluated by immunohistochemistry using the Hercep test. The
      results were scored into four levels by two pathologists; scores greater than 1+
      were considered positive. RESULTS: The HER-2 staining score was 0, 1+, 2+, 3+,
      and indeterminate in 28, 4, 11, 6, and 1 case, respectively. HER-2 was
      overexpressed (greater than 1+) in 21 patients (42%). The cause-specific survival
      and nonrecurrence rates were significantly lower in the HER-2-positive group than
      in the negative group (P = 0.0084 and P = 0.0485, respectively). Furthermore, the
      cause-specific survival rate after recurrence was significantly greater in the
      HER-2-negative group than in the positive group (P = 0.0247). CONCLUSIONS: We
      consider that HER-2 overexpression, as measured by immunohistochemistry, may be
      useful as a marker of an unfavorable prognosis by predicting the interval until
      relapse and outcome after endocrine therapy in patients with bone metastatic
      prostate cancer.

PMID- 16806434
TI  - Association of neoadjuvant hormonal therapy with adverse health-related quality
      of life after permanent iodine-125 brachytherapy for localized prostate cancer.
AB  - OBJECTIVES: To characterize the influence of neoadjuvant hormonal therapy (NHT)
      on health-related quality of life after permanent iodine-125 brachytherapy (BT)
      for prostate cancer. METHODS: A cross-sectional survey using the Expanded
      Prostate Cancer Index Composite health-related quality-of-life instrument was
      administered to 134 consecutive patients a median of 29 months after BT. A
      separate group of 111 patients with comparable demographic characteristics
      without any prior treatment for prostate cancer rendered the baseline information
      (control group). The scores and symptom rates were compared. The effect of NHT
      was tested for independence in a multivariate analysis. RESULTS: In contrast to
      patients who received NHT, prostatic edema was hardly detectable 30 days after
      implantation in patients who received BT alone (comparing median preimplant and
      postimplant volumes), resulting in a greater dose to the prostate and anterior
      rectal wall. However, compared with the control group and the patients who
      received BT alone, the addition of NHT to BT led to lower health-related quality
      of-life scores in all domains. Score differences of more than 10 points with a
      statistical significance were found for the urinary bother, sexual
      function/bother, and hormonal function/bother domains. Apart from the sexual
      function scores (patient age shown to be the crucial factor), the influence of
      NHT remained independent on multivariate analysis. CONCLUSIONS: The results
      stress the need for well-considered administration of NHT before BT and the need
      for reporting the use of NHT in studies dealing with BT-related toxicity.

PMID- 16806435
TI  - Development of an immunocytokine, IL-2-183B2scFv, for targeted immunotherapy of
      ovarian cancer.
AB  - OBJECTIVES: The purpose of this study was to develop an immunocytokine for
      immunotherapy of human ovarian cancer. METHODS: The single-chain Fv of a
      monoclonal antibody, COC183B2, specific for an ovarian carcinoma-associated
      antigen (OC183B2), was genetically fused with the coding sequence of interleukin
      2 (IL-2). The fusion protein, also called immunocytokine, IL-2-183B2scFv, was
      expressed in CHO cells and examined for its specificity and biological function.
      RESULTS: The immunocytokine, IL-2-183B2scFv, retained the functions of both the
      antibody and IL-2. It was able to target IL-2 to tumor cells that overexpress
      OC183B2, and stimulate the proliferation of an IL-2-dependent cell line, CTLL-2.
      CONCLUSIONS: The IL-2-183B2scFv maintains the functions of both IL-2 and
      antibody. It can be potentially used for immunotherapy of ovarian cancer by
      delivering a high concentration of IL-2 to OC183B2-expressing ovarian cancer
      cells.

PMID- 16806436
TI  - Role of appendectomy at the time of primary surgery in patients with early-stage
      ovarian cancer.
AB  - OBJECTIVE: To determine whether appendectomy is warranted in patients with
      apparent early-stage ovarian cancer who undergo surgery for staging and
      cytoreduction and to determine the complication rate associated with appendectomy
      in such patients. METHODS: We reviewed the medical records of all patients who
      underwent appendectomy at the time of primary surgery for ovarian cancer at The
      University of Texas M. D. Anderson Cancer Center between January 1992 and
      December 2004 and who did not meet any of the following exclusion criteria: stage
      III or IV ovarian cancer, appendectomy as part of a second-look procedure or
      secondary tumor-reductive surgery, primary appendiceal cancer, primary
      gastrointestinal malignancy with metastasis to the appendix, incomplete
      clinicopathologic data, appendicitis as a preoperative diagnosis, primary
      fallopian tube cancer, primary peritoneal cancer, or documented dual primary
      tumors. RESULTS: Fifty-seven patients were included in this analysis. The median
      age was 47 years (range, 13-75). Median follow-up was 53 months (range, 3-147).
      Histologic diagnoses were as follows: invasive epithelial carcinoma, 35 patients
      (61%); tumor of low malignant potential, 15 patients (26%); malignant germ cell
      tumor, 4 patients (7%); and other, 3 patients (5%). Twenty-three patients (40%)
      had pure mucinous tumors. Forty-six patients (81%) had stage I and 11 patients
      (19%) had stage II disease. The median CA-125 level was 36.2 U/mL (range, 7
      7900). No patient had evidence of appendiceal involvement. No patient suffered an
      intraoperative or postoperative complication directly related to appendectomy.
      CONCLUSIONS: Appendectomy at the time of surgery for apparent early-stage ovarian
      cancer is not associated with complications but should not be routinely
      recommended.

PMID- 16806437
TI  - Nucleotide excision repair genotype and the incidence of endometrial cancer:
      effect of other risk factors on the association.
AB  - OBJECTIVES: Certain nucleotide excision repair (NER) genotypes appear to be
      associated with an altered risk of endometrial cancer. These associations could
      be modified by characteristics and exposures that themselves influence risk of
      disease. METHODS: We conducted a population-based case-control study in western
      Washington State to address the role of specific NER genotypes in conjunction
      with relevant exposures, such as postmenopausal hormone therapy, obesity, parity,
      oral contraceptive use, and cigarette smoking on risk of endometrial cancer. Case
      women (n=371), ages 50-69 years, were diagnosed with invasive endometrial cancer
      between 1994 and 1999. Control women (n=420), matched to cases on age and county
      of residence, were selected using random-digit dialing (ages 50-65) and random
      selection from HCFA data files (ages 66-69). RESULTS: Risk of endometrial cancer
      was not associated with ERCC1, ERCC2 (XPD), ERCC4 (XPF), or ERCC5 (XPG) genotype.
      A reduced risk of endometrial cancer was observed with presence of the XPA g23a
      variant allele, but only among women with a history of oral contraceptive use (OR
      0.47, 95% CI 0.32-0.69). A decreased risk associated with carriage of at least
      one variant allele for both XPC A499V and XPC K939Q was restricted to women with
      BMI<30 kg/m2 (OR 0.45, 95% CI 0.25-0.82). The size of the association between
      these genotypes and risk of endometrial cancer did not differ by postmenopausal
      hormone use, parity, or smoking. CONCLUSIONS: Our study provides limited evidence
      for interactions between NER genotypes and DNA damage-causing exposures in the
      etiology of endometrial cancer. Subsequent studies are needed to confirm the
      observed associations.

PMID- 16806438
TI  - KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive
      carcinomas, borderline tumors and extraovarian implants.
AB  - OBJECTIVE: Mutations of BRAF, a downstream mediator of K-RAS, have been described
      in serous borderline tumors of the ovary. Data concerning other types of ovarian
      tumors are scarce. Therefore, we assessed KRAS and BRAF mutation in a series of
      more than 100 different ovarian tumors. METHODS: Paraffin-embedded material,
      including invasive carcinomas, borderline tumors, benign lesions and implants,
      was used. BRAF codon 600 in exon 15 and K-RAS codon 12 in exon 2 were analysed.
      RESULTS: 92 cases (92%), including all serous carcinomas (100%), did not show a
      mutation of BRAF. Eight cases (8.0%), including five serous borderline tumors
      (31.25%), contained a mutation. In all serous borderline tumors, codon 600 was
      affected. The remaining three cases were invasive carcinomas of endometrioid
      (mutation on codon 600), mucinous (mutation on codon 600) and clear cell
      (mutation on codon 615) subtype. There was no BRAF mutation in mucinous
      borderline tumors. Regarding K-RAS, 89 cases (87.25%) did not show an aberration.
      The 11 positive borderline tumors (10.7%) were of serous (22.2%) and of mucinous
      type (46.6%). There was a KRAS mutation in a serous and a mucinous invasive
      carcinoma each. BRAF and K-RAS mutations were mutually exclusive and not seen in
      implants. CONCLUSION: Mutation of either K-RAS or BRAF is frequent in borderline
      tumors but is not found in invasive serous carcinomas and is very rare in other
      invasive subtypes. This supports the notion of different pathological pathways.
      For the development of extraovarian implants, further studies are observed.

PMID- 16806439
TI  - Three sequential chemotherapy doublets for the treatment of newly diagnosed
      advanced mullerian malignancies: the modified triple doublet regimen.
AB  - OBJECTIVE: Previously, we reported the use of three sequential doublets (Triple
      Doublets) in the treatment of women with newly diagnosed and advanced stage
      mullerian malignancies. The surgically defined negative second look operation
      (SLO) rate to Triple Doublets was 38%. Modifications were made to this treatment
      regimen that were predicted to reduce toxicity and possibly increase efficacy.
      METHODS: Open label two-cohort study. Patients with a new diagnosis of Stages II
      IV mullerian malignancy were eligible. After cytoreductive surgery, patients were
      treated with three sequential doublets including 3 cycles of carboplatin and
      gemcitabine, and 3 cycles of carboplatin and paclitaxel, and 3 cycles of
      doxorubicin and topotecan. After therapy, all women were clinically staged and
      evaluated at SLO if clinical staging was negative for residual disease. Primary
      endpoints were toxicity and negative SLO rate with rates of 60% and 40% defined a
      priori in optimally cytoreduced (cohort 1) and suboptimally cytoreduced or Stage
      IV (cohort 2), respectively. RESULTS: Eighty-five eligible patients were enrolled
      with a median age of 52 years. Forty-seven and thirty-eight women were in cohorts
      1 and 2, respectively. 723 cycles of chemotherapy were delivered with no toxic
      deaths. Grades 3 and 4 toxicities included neutropenia in 75% of patients and
      thrombocytopenia in 65% of patients during at least one cycle of therapy. Fever
      and neutropenia were seen in 3.5% of patients. All Grades 3 and 4 non-hematologic
      toxicities were seen at a frequency of <10%. Seventy women underwent SLO with a
      negative SLO rate of 53% with an additional 9% having microscopically positive
      procedures. Negative SLO rate was 74% in cohort 1 and 36% in cohort 2.
      CONCLUSIONS: Treatment with the modified triple doublet regimen is tolerable with
      an encouraging pathologic CR rate.

PMID- 16806440
TI  - Evaluation of deletions in 7q11.2 and 8p12-p21 as prognostic indicators of tumour
      development following molar pregnancy.
AB  - OBJECTIVES: Previous studies have identified loss of chromosomal regions 7p12
      q11.2 and 8p12-p21 in choriocarcinoma suggesting that suppressor genes involved
      in tumour development may be located within these regions. Our objectives were to
      refine the regions of loss and evaluate these deletions as prognostic indicators
      of trophoblastic tumour development following molar pregnancy. METHODS:
      Fluorescent microsatellite genotyping was used to perform deletion mapping in a
      series of thirty-nine gestational trophoblastic tumours (GTT) including both
      choriocarcinoma and placental site trophoblastic tumours. RESULTS: Significant
      loss of heterozygosity (LOH) was found for both regions in GTT that originated in
      non-molar pregnancies. Although no common interval of loss was found in those GTT
      with LOH for the 7q11.2 region, for the 8p12-p21 locus, markers D8S1731 and NEFL
      defined a minimal region of loss in all tumours showing LOH. However, complete
      LOH of either region occurred in only a minority of tumours (20%; chromosome 7:
      24%; chromosome 8) suggesting that loss of neither region is likely to be a
      primary event in the development of GTT. This was further supported by the
      observation that no deletions were found in either region for the fourteen GTT
      that followed complete molar pregnancies. CONCLUSIONS: While we have defined a
      minimal interval in 8p12-p21 in which tumour suppressor genes involved in GTT are
      likely to be located, the data suggest that deletions in 7q11.2 or 8p12-p21 are
      unlikely to be useful prognostic indicators in the management of patients with
      molar pregnancies.

PMID- 16806441
TI  - The reinforcement of invasion in epithelial ovarian cancer cells by 17 beta
      Estradiol is associated with up-regulation of Snail.
AB  - OBJECTIVE: The transcription factor Snail, which is implicated in the triggering
      of epithelial-mesenchymal transitions (EMT), plays an important role in adhesion,
      invasion and metastasis of tumor cells. In the present study, we assessed 17beta
      Estradiol (E2)'s effect on Snail, E-cadherin and MMP-2 expression of epithelial
      ovarian cancer cell line ES-2 and SKOV3. Then we induced Snail gene silencing by
      RNA interference to explore the effect of E2 on E-cadherin and MMP-2 expression
      when Snail gene expression was blocked. METHODS: Treated by 10(-8) M E2, Snail, E
      cadherin and MMP-2 mRNA expression of the cells was measured by RT-PCR; Snail,
      MMP-2 protein expression was detected by IHC; and MMP-2 activity was determined
      by Zymography. E-cadherin protein level was measured by Western blot. We
      constructed the small interfering dsRNA expression vector (pRNAT-U6.1/Neo-Snail)
      targeting Snail gene, as well as a negative control vector (pRNAT-U6.1/Neo-Neg).
      Then the cells were transiently transfected with the vectors. Western blot and
      zymography were conducted to determine E-cadherin protein level and matrix
      metalloproteinase activity of the cells transfected with pRNAT-U6.1/Neo-Snail or
      pRNAT-U6.1/Neo-Neg after treated with E2 for 24 h. RESULTS: The expression of ER
      alpha mRNA and protein was negative in ES-2 cells and positive in SKOV3 cells,
      and ER beta expression was positive in both cell lines. 10(-8) mol/l E2 elevated
      expression of Snail and MMP-2 mRNA and protein in both ES-2 and SKOV3 cells, and
      reduced expression of E-cadherin mRNA and protein in SKOV3 cells. While in the
      RNAi group transfected with the small interfering dsRNA expression vector (pRNAT
      U6.1/Neo-Snail) targeting Snail gene, E2 treatment did not have a significant
      effect on MMP-2 activity or E-cadherin protein in ES-2 and SKOV3 cells.
      CONCLUSIONS: 17beta-Estradiol increased Snail expression in both ER alpha
      negative ES-2 cells and ER alpha-positive SKOV3 cells independent of the
      existence of ER alpha. The increase of MMP-2 expression in ES-2 and SKOV3 cells
      and decrease of E-cadherin expression in SKOV3 cells induced by E2 were
      associated with up-regulation of Snail.

PMID- 16806442
TI  - Pelvic lymphadenectomy for cervical carcinoma: laparotomy extraperitoneal,
      transperitoneal or laparoscopic approach? A randomized study.
AB  - OBJECTIVE: To compare transperitoneal, extraperitoneal and laparoscopic pelvic
      lymphadenectomy in terms of feasibility and morbidity in patients affected by
      cervical cancer undergoing radical hysterectomy. METHODS: Consecutive patients
      affected by stage IB-IIB cervical carcinoma scheduled for radical surgery entered
      the study. Patients were randomly assigned to transperitoneal (TPL),
      extraperitoneal (EPL) or laparoscopic pelvic lymphadenectomy (LPL). All patients
      underwent classical radical hysterectomy. Perioperative data were recorded.
      Follow up examinations were performed at the 15th, 30th and 60th day after
      surgery. RESULTS: 168 patients entered the study. The mean operative times were:
      63+/-7.6, 54+/-6.7 and 75+/-8.4 min (TPL vs EPL P<0.001; EPL vs LPL P<0.001; TPL
      vs LPL P<0.001) for TPL, EPL and LPL respectively. The feasibility of the
      procedures, analyzed on an intention-to-treat basis, was 96%, 93% and 95% for
      TPL, EPL and LPL group respectively (P=ns). The average hospitalizations were:
      5.6+/-0.9, 3.2+/-0.4 and 3.1+/-0.3 days (TPL vs EPL P<0.001; TPL vs LPL P<0.001)
      for TPL, EPL and LPL respectively. CONCLUSIONS: EPL and LPL are as feasible and
      effective as TPL and can be adequately performed with a reasonable complication
      rate. LPL showed a statistically significant longer operative time. However, both
      EPL and LPL can minimize some postoperative complications reducing length of
      stay.

PMID- 16806443
TI  - Multiple vaccine and pyridostigmine interactions: effects on cognition, muscle
      function and health outcomes in marmosets.
AB  - Following active service during the 1990/1991 Gulf Conflict, a number of UK and
      US veterans presented with a diverse range of symptoms, collectively known as
      Gulf Veterans Illnesses (GVI). The administration of vaccines and/or the
      pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB),
      given to armed forces personnel during the Gulf Conflict has been implicated as a
      possible factor in the aetiology of these illnesses. The possibility that long
      term health effects may result from the administration of these vaccines
      (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B,
      meningococcal meningitis and cholera) and/or PB, have been investigated using a
      non-human primate model, the common marmoset. This paper reports the results from
      three aspects of the study, cognitive behaviour (performance of a touchscreen
      mediated discrimination task), muscle function (performance of a simple strength
      test) and general health. There were no marked long-term changes in cognition,
      muscle function or health that could be attributed to vaccines and/or PB
      administration. Statistical differences related to treatments were only observed
      in two aspects of cognition and one of clinical chemistry. These changes were
      transient in nature and their magnitude were minor and, in consequence, was not
      regarded as having long-term biological significance.

PMID- 16806444
TI  - The effects of long-term chronic buprenorphine treatment on the locomotor and
      nucleus accumbens dopamine response to acute heroin and cocaine in rats.
AB  - We have previously shown that chronic treatment with the partial mu-opioid
      receptor agonist, buprenorphine, blocks the nucleus accumbens dopamine response
      to an acute injection of heroin, whereas it potentiates the response to an acute
      injection of cocaine after 4-5 days of treatment. Here we studied the effects of
      chronic exposure to buprenorphine via osmotic minipumps for up to 28 days (1.5 or
      3.0 mg/kg/day) on responses to acute injections of heroin and cocaine. Increases
      in locomotion induced by heroin (0.25 mg/kg, sc), given on the 5th, 15th or 25th
      day of treatment were unaffected by buprenorphine, whereas increases induced by
      cocaine (20 mg/kg, ip) were enhanced early in treatment but not on the 15th or
      25th days. Using in vivo microdialysis we found that both the suppression of the
      dopaminergic response in the nucleus accumbens to heroin and the potentiation to
      cocaine seen early in treatment diminished over the 26-27 days, whereas basal
      dopamine levels remained elevated throughout. Therefore, although these studies
      do not explain the mechanism whereby buprenorphine reduces heroin and cocaine
      intake, they do indicate that there is little tolerance to the presence of
      chronic buprenorphine.

PMID- 16806445
TI  - Effect of MK-801 and ketamine on hydroxyl radical generation in the posterior
      cingulate and retrosplenial cortex of free-moving mice, as determined by in vivo
      microdialysis.
AB  - This study investigated the effect of MK-801 and ketamine, N-methyl-D-aspartate
      (NMDA) receptor antagonists which can induce schizophrenic symptoms and have
      neurotoxicity in human and animals, on hydroxyl radical (*OH) generation in the
      posterior cingulate and retrosplenial (PC/RS) cortex of free-moving mice using
      the salicylic acid trapping technique. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg)
      acute administration significantly increased *OH levels in mouse PC/RS cortex.
      The basal *OH levels after MK-801 and ketamine administrations for 7 consecutive
      days were significantly increased compared with the naive basal levels. MK-801
      (0.6 mg/kg) or ketamine (50 mg/kg) challenge after chronic administration further
      significantly increased dialysate levels of *OH. Our study also found that the
      release of *OH was secondary to stereotyped behavior, and the intensity of
      stereotyped behavior induced by MK-801 was more than that induced by ketamine.
      The results suggested that NMDA receptor antagonists participate in the
      generation of *OH in the PC/RS cortex of mouse, and oxidative stress, derived
      from the formation of free radicals, might play an important role in the
      pathophysiology of these two models of schizophrenia.

PMID- 16806447
TI  - A peer-modeling and rewards-based intervention is effective in increasing fruit
      and vegetable consumption in children.

PMID- 16806448
TI  - Luteal and follicular count in bitches: assessment by means of magnetic resonance
      imaging.
AB  - This study was done to determine whether preovulatory follicles or corpora lutea
      (physiological structures, PS) can be counted in the ovaries of bitches by means
      of magnetic resonance imaging (MRI). In Experiment 1, the ovaries from 15 German
      shepherd bitches (five in the follicular phase, one in the periovulatory period,
      five during the first 38 days of diestrus and four between Day 48 of diestrus and
      full-term gestation) were embedded in gelatin to form three phantoms with 10
      ovaries each. Each phantom was exposed to MRI, using a 1mm slice thickness, a 1mm
      slice interval, a voxel size of 1mm cubic and a variety of pulse sequences,
      whereafter the ovaries were dissected and the numbers of follicles, corpora lutea
      and cysts counted. T2-weighted images were superior to T1-weighted images. Each
      of three operators counted the numbers of PS and cysts on T2-weighted images
      obtained in the coronal, transverse and sagital planes of each ovary, which, for
      the 30 ovaries, provided 270 operator by ovary by plane estimations and 90
      operator by ovary estimations for each type of structure. Images of cysts were
      hyperintense, those of early corpora lutea and follicles similar and moderate and
      those of late corpora lutea hypo-intense and not clearly discernable from ovarian
      stroma. Estimations of PS were too low in 68%, correct in 12% and too high in 20%
      of estimations (n=270). Estimations of PS were correct in three operator by ovary
      combinations, out by 1 in 22 and out by more than 1 in 65. No operator estimated
      PS correctly in any bitch. In Experiment 2 MRI was done on three deeply sedated
      bitches in the periovulatory phase in an attempt to obtain images of the ovaries
      in order to count the follicles. The acquisition time of 5-7 min rendered images
      of poor quality from live bitches and none of their ovaries could be seen. MRI is
      not suitable for counting follicles or corpora lutea in the ovaries of bitches.

PMID- 16806449
TI  - Freezing of in vitro produced bovine embryos in animal protein-free medium
      containing vegetal peptones.
AB  - Successful cryopreservation is essential for a large-scale dispersal of bovine in
      vitro produced (IVP) embryos that have been shown to be more sensitive to
      cryopreservation than their in vivo counterparts. On the other hand, the use of
      animal proteins in freezing media increases sanitary risks. We first replaced
      animal proteins, such as bovine serum albumin (BSA) in the freezing medium by
      plant-derived peptides (vegetal peptones). A batch of wheat peptones was selected
      after a preliminary experiment showing the absence of toxicity of
      concentrations<18 mg/mL on in vitro bovine blastocysts. Increasing concentrations
      of peptones were then added in the freezing medium. The surviving and hatching
      rates were not affected by comparison with those observed with BSA. No
      significant difference was observed between groups either for the total number of
      cells or for the ratio ICM/Total cell, nor for the rate of apoptosis in surviving
      embryos. When embryos were cryopreserved in 1.8 mg/mL peptone, the hatching rate
      and embryo quality as assessed at 48 h post-thawing were not significantly
      different from those of unfrozen embryos. In a second experiment two additives
      were added in this animal protein-free freezing medium containing 1.8 mg/mL
      peptones. No beneficial effect of adding 1 mg/mL sodium hyaluronate or 100 microM
      beta-mercaptoethanol was observed on embryo survival or quality. In conclusion,
      we have demonstrated that vegetal peptones can replace BSA in freezing media
      without affecting blastocyst survival and quality.

PMID- 16806450
TI  - Laparoscopic ovum pick-up and in vitro production of sika deer embryos: effect of
      season and culture conditions.
AB  - Amongst the 200 deer subspecies worldwide, more than 40 are considered as
      endangered. In vitro embryo production may represent an efficient way to produce
      and disseminate offspring from sparse remaining individuals in these species.
      With a view to establishing a method of in vitro embryo production, we assessed
      the ovarian response after hormonal stimulation (oFSH), oocyte yield following
      laporoscopic ovum pick-up (LOPU) and oocyte developmental competence according to
      seasonal reproductive status in sika deer (Cervus nippon nippon). Twelve adult
      sika deer hinds were allocated between two groups and submitted weekly to oFSH
      follicular growth stimulation followed by LOPU. Hinds in Group A (n=6) were
      treated first during the breeding season (5 weeks), and then during the non
      breeding season (3 weeks). Hinds in Group B (n=6) were submitted to similar
      procedures but in the reverse order (treated first during the non-breeding
      season). Cumulus-oocytes complexes (COC) recovered from Group B were allowed to
      mature in vitro for 24 h in TCM-199 medium supplemented with oFSH, goat
      follicular fluid and 100 microM cysteamine. In vitro fertilization was performed
      with frozen/thawed semen in SOFaa medium supplemented with 20% estrous sheep
      serum and presumptive zygotes were cultured in the presence or absence of ovine
      oviductal epithelial cell monolayer (oOEC) in SOFaa-BSA medium. Mean number of
      follicles aspirated per hind per session decreased significantly between breeding
      and non-breeding season in Group A (9.8+/-0.7 versus 3.2+/-0.7, mean+/-S.E.M.,
      respectively, P<0.001) but did not change between the non-breeding and the
      subsequent breeding season in Group B (5.3+/-0.7 and 5.7+/-0.7, respectively,
      P>0.05). Irrespective of the season, good quality COC with complete and compact
      cumulus investments were recovered allowing a high cleavage rate after in vitro
      maturation and fertilization. Whereas development to the blastocyst stage did not
      occur in SOF medium alone, high development rates to the blastocyst stage were
      observed in oOEC co-culture regardless of season (22% and 34% of total oocytes in
      co-culture during non-breeding and breeding season, respectively).

PMID- 16806451
TI  - Reproductive performance of gilts following vaccination and subsequent
      heterologous challenge with European strains of porcine reproductive and
      respiratory syndrome virus.
AB  - The objective of this study was to evaluate the efficacy of two commercially
      available modified live virus vaccines for preventing the reproductive and early
      postnatal consequences of infecting (challenging) pregnant gilts with virulent
      porcine reproductive and respiratory syndrome virus (PRRSV). For this purpose 21
      crossbred gilts were allocated to one or another of four groups (Groups A-D).
      Group A comprised four gilts neither vaccinated nor challenged; Group B comprised
      five gilts that were challenged but not vaccinated; Group C comprised seven gilts
      that were vaccinated (AmervacPRRS) and challenged; Group D comprised five gilts
      that were vaccinated (Pyrsvac-183) and challenged. Vaccination was 24 days before
      conception, and challenge was at 90 days of gestation. Both vaccine viruses and
      the challenge virus were European strains but differed in part from one another
      on the basis of their genetic (nucleotide) sequence. After challenge PRRSV was
      isolated from five (100%), four (57%), and two (40%) of the gilts of Groups B, C
      and D, respectively. Although vaccination failed to prevent a detectable viremia
      in all of the gilts of Groups C and D after they were challenged (or congenital
      infection of some of their pigs), it did provide a statistically significant
      level of protection in regard to the incidence of congenital infection,
      reproductive performance, and pig health and viability. Namely, for Groups C and
      D the numbers of liveborn pigs/litter and healthy pigs/litter throughout the
      early postnatal period were similar to those of Group A (nonvaccinated and
      nonchallenged) and far exceeded those of Group B (nonvaccinated and challenged).

PMID- 16806452
TI  - A comparison of fatigue crack growth in resin composite, dentin and the
      interface.
AB  - OBJECTIVES: The objective of this in vitro study was to evaluate the fatigue
      crack growth properties of the dentin/resin adhesive interface. METHODS: Compact
      tension (CT) specimens were prepared from coronal dentin, resin composite, and
      dentin bonded to resin composite using Optibond Solo Plus adhesive. All specimens
      were then subjected to cyclic Mode I loading while fully hydrated at a stress
      ratio of R=0.1 and frequency of 5 Hz. Steady state fatigue crack growth was
      modeled using the Paris Law in terms of the exponent (m) and coefficient (C).
      RESULTS: The average fatigue crack growth rates in the resin composite ranged
      from 1.6E-06 to 3.8E-05 mm/cycle with growth occurring over a stress intensity
      range from 0.40 to 0.77 MPa m(1/2); the average growth exponent was 6.9+/-3.1.
      Average fatigue crack growth rates for the dentin/resin interface specimens
      ranged from 5.5E-07 to 6.4E-03 mm/cycle with growth occurring over a stress
      intensity range from 0.37 to 0.64 MPa m(1/2). The Paris Law exponent for these
      specimens ranged from 16<or=m<or=25. Fatigue crack growth at the interface
      occurred primarily in the adhesive resin and at the adhesive-dentin interface. In
      addition, many of the dentin/resin specimens underwent unstable fracture at a
      comparatively low stress intensity range without undergoing cyclic crack growth.
      SIGNIFICANCE: The dentin/resin adhesive interface proved to be significantly more
      sensitive to fatigue crack growth than either dentin or resin composite.
      Variation in the cyclic crack growth responses of the dentin/resin interface
      specimens suggests that the interface, and particularly the adhesive resin,
      exhibits lower resistance to crack initiation and growth in comparison to dentin.

PMID- 16806453
TI  - Thermal and rheological properties of nixtamalized maize starch.
AB  - The effect of nixtamalization process on thermal and rheological characteristics
      of corn starch was studied. Starch of raw sample had higher gelatinization
      temperature than its raw counterpart, because, the Ca(2+) ions stabilize starch
      structure of nixtamalized sample; however, the enthalpy values were not different
      in both samples. The temperature of the phase transition of the retrograded
      starches (raw and nixtamalized) were not different at the storage times assessed,
      but the enthalpy values of the above mentioned transition was different,
      indicating a lower reorganization of the starch structure in the nixtamalized
      sample. The viscoamylographic profile showed differences between both starches,
      since raw starch had higher peak viscosity than the nixtamalized sample due to
      partial gelatinization of some granules during this heat treatment. Rheological
      test showed that at low temperature (25 degrees C) the raw and nixtamalized
      starches presented different behaviour; however, the elastic characteristic was
      more important in the starch gel structure. The nixtamalization process produced
      changes in thermal and rheological characteristics becoming important in those
      products elaborated from nixtamalized maize.

PMID- 16806454
TI  - The development and characterization of a glutathione-sensitive cross-linked
      polyethylenimine gene vector.
AB  - A glutathione-sensitive cross-linked polyethylenimine gene vector CLPEI(50%) was
      specially designed via the cross-linking reaction between the low molecular
      weight polyethylenimine (PEI(1800)) and dimethyl 3.3'-dithiopropionimidate
      dihydrochloride (DTBP). The acid-base titration test indicated that CLPEI(50%)
      still possessed efficient proton sponge effect. The property of CLPEI(50%)-DNA
      complexes were investigated by atomic force microscopy (AFM) and dynamic light
      scattering (DLS). CLPEI(50%) induced DNA condensation and formed spherical
      nanoparticles. The diameter of polyplexes prepared at pH value of 6.0 and 7.4 was
      about 150 and 260 nm, respectively. It was interesting to find the polyplexes
      were sensitive to the reductive glutathione (GSH). The CLPEI(50%)-DNA polyplexes
      prepared at N/P ratio of 10 were unpacked at GSH concentration of 3mm, which was
      comparable to the intracellular environment. The in vitro cytotoxicity of
      CLPEI(50%) was also significantly reduced comparing with PEI(25k). The biomimetic
      CLPEI(50%)-DNA polyplexes with the low cytotoxicity and GSH-sensitive property
      could be a good candidate for gene delivery.

PMID- 16806455
TI  - Ni(II) activates the Nrf2 signaling pathway in human monocytic cells.
AB  - Nickel is a component of biomedical alloys that is released during corrosion and
      causes inflammation in tissues by as yet unknown mechanisms. Recent data show
      that Ni(II) at concentrations of 10-50 microM amplifies lipopolysaccharide
      triggered, NFkappaB-mediated cytokine secretion from monocytes. In the current
      study, we tested the hypothesis that Ni(II) amplifies cytokine secretion by
      activating the Nrf2 antioxidant pathway rather than by enhancing activity of the
      NFkappaB signaling pathway. Human THP1 monocytes were exposed to Ni(II)
      concentrations of 10-30 microM for 6-72 h, then immunoblots of whole-cell lysates
      or cytosolic and nuclear proteins were used to detect changes in Nrf2 or NFkappaB
      signaling. Our results show that Ni(II) increased (by 1-2 fold) whole-cell Nrf2
      levels and nuclear translocation of Nrf2, and amplified lipopolysaccharide (LPS)
      induction of Nrf2 (by 3-5 fold), but had no detectable effect on the initial
      activation or nuclear translocation of NFkappaB. Because Nrf2 target gene
      products are known regulators of NFkappaB nuclear activity, our results suggest
      that Ni(II) may affect cytokine secretion indirectly via modulation of the Nrf2
      pathway.

PMID- 16806456
TI  - Heparin-regulated release of growth factors in vitro and angiogenic response in
      vivo to implanted hyaluronan hydrogels containing VEGF and bFGF.
AB  - Controlled release of human vascular endothelial growth factor (VEGF) or basic
      fibroblast growth factor (bFGF) from hydrogels composed of chemically modified
      hyaluronan (HA) and gelatin (Gtn) was evaluated both in vitro and in vivo. We
      hypothesized that inclusion of small quantities of heparin (Hp) in these gels
      would regulate growth factor (GF) release over an extended period, while still
      maintaining the in vivo bioactivity of released GFs. To test this hypothesis, HA,
      Gtn, and Hp (15 kDa) were modified with thiol groups, then co-crosslinked with
      poly (ethylene glycol) diacrylate (PEGDA). Either VEGF or bFGF was incorporated
      into the gels before crosslinking with PEGDA. Release of these GFs in vitro could
      be sustained over 42 days by less than 1% Hp content, and was found to decrease
      monotonically with increasing Hp concentration. As little as 0.03% Hp in the gels
      reduced the released VEGF fraction from 30% to 21%, while 3% Hp reduced it to
      19%. Since the minimum Hp concentration capable of effective controlled GF
      release in vitro was found to be 0.3% (w/w), this concentration was selected for
      subsequent in vivo experiments. To evaluate the bioactivity of released GFs in
      vivo, gel samples were implanted into the ear pinnas of Balb/c mice and the
      resulting neovascularization response measured. In the presence of Hp,
      vascularization was sustained over 28 days. GF release was more rapid in vitro
      from gels containing Gtn than from gels lacking Gtn, though unexpectedly, the in
      vivo neovascularization response to Gtn-containing gels was decreased.
      Nevertheless significant numbers of neovessels were generated. The ability to
      stimulate localized microvessel growth at controlled rates for extended times
      through the release of GFs from covalently linked, Hp-supplemented hydrogels will
      ultimately provide a powerful therapeutic tool.

PMID- 16806457
TI  - Equibiaxial strain stimulates fibroblastic phenotype shift in smooth muscle cells
      in an engineered tissue model of the aortic wall.
AB  - Many cells in the body reside in a complex three-dimensional (3D) environment
      stimulated by mechanical force. In vitro bioreactor systems have greatly improved
      our understanding of the mechanisms behind cell mechanotransduction. Current
      systems to impose strain in vitro are limited either by the lack of uniform
      strain profile or inability to strain 3D engineered tissues. In this study, we
      present a system capable of generating cyclic equibiaxial strain to an engineered
      vascular wall model. Type I collagen hydrogels populated with rat aortic smooth
      muscle cells (RASMCs) were created either as a compacting disk or constrained
      hemisphere. Both models were adhered to silicone membranes precoated with
      collagen I, fibronectin, or Cell-Tak and assayed for adhesion characteristics.
      The best performing model was then exposed to 48 h of 10% strain at 1Hz to
      simulate wall strain profiles found in vascular aneurysms, with static cultures
      serving as controls. The finite strain profile at the level of the membrane and
      the free surface of the construct was quantified using microbeads. The results
      indicate that the hemisphere model adhered with Cell-Tak had the most stable
      adhesion, followed by fibronectin and collagen I. Disk models did not adhere well
      under any coating condition. Uniform strain propagation was possible up to a
      maximum area strain of 20% with this system. RASMC responded to 10% equibiaxial
      strain by becoming less elongated, and immunohistochemistry suggested that
      stretched RASMC shifted to a more synthetic phenotype in comparison to static
      controls. These results suggest that equibiaxial strain may induce smooth muscle
      cell differentiation. We conclude that this system is effective in stimulating
      cells with cyclic equibiaxial strain in 3D cultures, and can be applied to a
      variety of biomaterial and tissue engineering applications.

PMID- 16806458
TI  - The in vitro adsorption of cytokines by polymer-pyrolysed carbon.
AB  - This study investigated a range of phenol-formaldehyde-aniline-based pyrolysed
      carbon matrices and their component materials, for their ability to adsorb a
      range of inflammatory cytokines crucial to the progression of sepsis. The
      efficiency of adsorption of the target molecules from human plasma was assessed
      and compared to that of Adsorba 300C, a commercially available cellulose-coated
      activated charcoal. Results indicate that a number of the primary carbon/resin
      materials demonstrate efficient adsorption of the cytokines studied here (TNF, IL
      6 and IL-8), comparable to other adsorbents under clinical investigation. Our
      findings also illustrate that these adsorbent capabilities are retained when the
      primary particles are combined to form a pyrolysed carbon matrix. This capability
      will enable the engineering of the carbon matrix porosity allowing a blend of
      carbonised particle combinations to be tailored for maximum adsorption of
      inflammatory cytokines. The present findings support further investigation of
      this carbon material as a combined carbon-based filtration/adsorbent device for
      direct blood purification.

PMID- 16806459
TI  - The correlation of RANK, RANKL and TNFalpha expression with bone loss volume and
      polyethylene wear debris around hip implants.
AB  - This study investigates receptor activator NF-kappaB (RANK), RANK ligand (RANKL)
      and tumour necrosis factor (TNFalpha), key factors regulating bone turnover,
      present in the tissues near peri-prosthetic osteolysis. Tissue was obtained from
      zones of peri-prosthetic osteolysis from 11 patients undergoing revision of total
      hip prostheses, analysed preoperatively by high-resolution spiral multislice CT
      using a metal artefact suppression protocol. Synovial tissue from 10 patients
      with osteoarthritis undergoing primary hip replacement was used as control
      tissue. Immunohistochemical analysis of formalin fixed tissue sections
      demonstrated that RANK, RANKL and TNFalpha were strongly expressed by large
      multinucleated cells containing polyethylene wear debris in revision tissues.
      Control tissue stained weakly for RANK, RANKL and TNFalpha. A strong statistical
      correlation (p<0.02) was found between the five parameters, volume of bone loss,
      polyethylene wear debris, RANK, RANKL and TNFalpha expression. Importantly, in
      vitro studies revealed that RANKL and TNFalpha synergise to increase the volume
      of bone resorbed, by more than seven fold, when compared to the effect of either
      cytokine treatment alone. This suggests that the interaction of TNFalpha and
      RANKL promotes osteoclast activity associated with polyethylene wear and
      therapies targeting TNF activity may be useful to treat peri-implant osteolysis.

PMID- 16806460
TI  - Long telomeres in the mature human placenta.
AB  - OBJECTIVE: To investigate whether telomere shortening may play a role in
      senescence of the placenta. STUDY DESIGN: Villous tissue was collected from
      single, random sites of full-term placentas (39-41 weeks of gestation; n=10) as
      well as multiple, specific sites of the same placenta (39-41 weeks of gestation;
      n=5). For the latter group of placentas, samples were taken near the umbilical
      cord and at the periphery on both the maternal and fetal sides (a total of 4
      samples per placenta). Cord blood samples were also obtained from all placental
      donors. Telomerase activity was assessed by the TRAP assay, and telomere length
      measured by Southern analysis of mean terminal restriction fragment (TRF) length.
      RESULTS: We show for the first time that telomeres are longer ( approximately 25%
      longer; P<0.001) in placenta tissue than in cord blood from the same donor.
      CONCLUSION: Telomere shortening is unlikely to have a significant role in
      senescence or terminal maturation of the placenta.

PMID- 16806461
TI  - TRP channels and Ca2+ signaling.
AB  - There is a rapidly growing interest in the family of transient receptor potential
      (TRP) channels because TRP channels are not only important for many sensory
      systems, but they are crucial components of the function of neurons, epithelial,
      blood and smooth muscle cells. These facts make TRP channels important targets
      for treatment of diseases arising from the malfunction of these channels in the
      above cells and for treatment of inflammatory pain. TRP channels are also
      important for a growing number of genetic diseases arising from mutations in
      various types of TRP channels. The Minerva-Gentner Symposium on TRP channels and
      Ca(2+) signaling, which took place in Eilat, Israel (February 24-28, 2006) has
      clearly demonstrated that the study of TRP channels is a newly emerging field of
      biomedicine with prime importance. In the Eilat symposium, investigators who have
      contributed seminal publications and insight into the TRP field presented their
      most recent, and in many cases still unpublished, studies. The excellent
      presentations and excitement generated by them demonstrated that much progress
      has been achieved. Nevertheless, it was also evident that the field of TRP
      channels is still in its infancy in comparison to other fields of ion channels,
      and even the fundamental knowledge of the gating mechanism of TRP channels is
      still unsolved. The beautiful location of the symposium, together with informal
      intensive discussions among the participants, contributed to the success of this
      meeting.

PMID- 16806462
TI  - Mitochondria buffer NCX-mediated Ca2+-entry and limit its diffusion into vascular
      smooth muscle cells.
AB  - The reverse-mode of the Na(+)/Ca(2+)-exchanger (NCX) mediates Ca(2+)-entry in
      agonist-stimulated vascular smooth muscle (VSM) and plays a central role in salt
      sensitive hypertension. We investigated buffering of Ca(2+)-entry by peripheral
      mitochondria upon NCX reversal in rat aortic smooth muscle cells (RASMC).
      [Ca(2+)] was measured in mitochondria ([Ca(2+)](MT)) and the sub-plasmalemmal
      space ([Ca(2+)](subPM)) with targeted aequorins and in the bulk cytosol
      ([Ca(2+)](i)) with fura-2. Substitution of extracellular Na(+) by N-methyl-d
      glucamine transiently increased [Ca(2+)](MT) ( approximately 2microM) and
      [Ca(2+)](subPM) ( approximately 1.3microM), which then decreased to sustained
      plateaus. In contrast, Na(+)-substitution caused a delayed and tonic increase in
      [Ca(2+)](i) (<100nM). Inhibition of Ca(2+)-uptake by the sarcoplasmic reticulum
      (SR) (30microM cyclopiazonic acid) or mitochondria (2microM FCCP or 2microM
      ruthenium red) enhanced the elevation of [Ca(2+)](subPM). These treatments also
      abolished the delay in the [Ca(2+)](i) response to 0Na(+) and increased its
      amplitude. Extracellular ATP (1mM) caused a peak and plateau in [Ca(2+)](i), and
      only the plateau was inhibited by KB-R7943 (10microM), a selective blocker of
      reverse-mode NCX. Evidence for ATP-mediated NCX-reversal was also found in
      changes in [Na(+)](i). Mitochondria normally exhibited a transient elevation of
      [Ca(2+)] in response to ATP, but inhibiting the mitochondrial NCX with CGP-37157
      (10microM) unmasked an agonist-induced increase in mitochondrial Ca(2+)-flux.
      This flux was blocked by KB-R7943. In summary, mitochondria and the sarcoplasmic
      reticulum co-operate to buffer changes in [Ca(2+)](i) due to agonist-induced NCX
      reversal.

PMID- 16806464
TI  - A constitutively active nonselective cation conductance underlies resting Ca2+
      influx and secretion in bovine adrenal chromaffin cells.
AB  - We have combined fluorimetric measurements of the intracellular free Ca(2+)
      concentration ([Ca(2+)](i)) with the patch clamp technique, to investigate
      resting Ca(2+) entry in bovine adrenal chromaffin cells. Perfusion with nominally
      Ca(2+)-free medium resulted in a rapid, reversible decrease in [Ca(2+)](i),
      indicating a resting Ca(2+) permeability across the plasma membrane. Simultaneous
      whole-cell voltage-clamp showed a resting inward current that increased when
      extracellular Ca(2+) (Ca(2+)(o)) was lowered. This current had a reversal
      potential of around 0 mV and was carried by monovalent or divalent cations. In
      Na(+)-free extracellular medium there was a reduction in current amplitude upon
      removal of Ca(2+)(o), indicating the current can carry Ca(2+). The current was
      constitutively active and not enhanced by agents that promote Ca(2+)-store
      depletion such as thapsigargin. Extracellular La(3+) abolished the resting
      current, reduced resting [Ca(2+)](i) and inhibited basal secretion. Abolishment
      of resting Ca(2+) influx depleted the inositol 1,4,5-trisphosphate-sensitive
      Ca(2+) store without affecting the caffeine-sensitive Ca(2+) store. The results
      indicate the presence of a constitutively active nonselective cation conductance,
      permeable to both monovalent and divalent cations, that can regulate [Ca(2+)](i),
      the repletion state of the intracellular Ca(2+) store and the secretory response
      in resting cells.

PMID- 16806465
TI  - The pharmacology and regulation of T type calcium channels: new opportunities for
      unique therapeutics for cancer.
AB  - T type calcium channels are implicated in a fascinating array of physiological
      and pathophysiological phenomena, as reviewed extensively in this issue of Cell
      Calcium. It is also evident from this timely collection of papers that knowledge
      about T channels is nascent. This creates the exciting potential to explore an
      uncharted territory for new insights into important physiological processes and
      associated diseases. Equally exciting and perhaps more important is the
      opportunity to exploit the developing understanding of T channels to design new
      therapeutic approaches to diseases that are now intractable to varying degrees.
      This review will focus on the controversy surrounding the proposed novel
      functions for and means of regulation of T type Ca2+ channels, particularly with
      regard to the potential role of pharmacologic modulation of T type Ca2+ channels
      in cytostatic cancer chemotherapy. In addition, we will concentrate on recent
      studies of the molecular pharmacology and physiology of T type channels, since
      these areas (molecular pharmacology [T.N. Heady, J.C. Gomora, T.L. Macdonald, E.
      Perez-Reyes, Molecular pharmacology of T-type Ca2+ channels, Jpn. J. Pharmacol.
      85 (2001) 339-350.]; physiology [E. Perez-Reyes, Molecular physiology of low
      voltage-activated t-type calcium channels, Physiol. Rev. 83 (2003) 117-161.])
      have been very well-reviewed and the reader is referred to these authoritative
      sources.

PMID- 16806463
TI  - TRPM4 controls insulin secretion in pancreatic beta-cells.
AB  - TRPM4 is a calcium-activated non-selective cation channel that is widely
      expressed and proposed to be involved in cell depolarization. In excitable cells,
      TRPM4 may regulate calcium influx by causing the depolarization that drives the
      activation of voltage-dependent calcium channels. We here report that insulin
      secreting cells of the rat pancreatic beta-cell line INS-1 natively express TRPM4
      proteins and generate large depolarizing membrane currents in response to
      increased intracellular calcium. These currents exhibit the characteristics of
      TRPM4 and can be suppressed by expressing a dominant negative TRPM4 construct,
      resulting in significantly decreased insulin secretion in response to a glucose
      stimulus. Reduced insulin secretion was also observed with arginine vasopressin
      stimulation, a Gq-coupled receptor agonist in beta-cells. Moreover, the
      recruitment of TRPM4 currents was biphasic in both INS-1 cells as well as HEK-293
      cells overexpressing TRPM4. The first phase is due to activation of TRPM4
      channels localized within the plasma membrane followed by a slower secondary
      phase, which is caused by the recruitment of TRPM4-containing vesicles to the
      plasma membrane during exocytosis. The secondary phase can be observed during
      perfusion of cells with increasing [Ca(2+)](i), replicated with agonist
      stimulation, and coincides with an increase in cell capacitance, loss of FM1-43
      dye, and vesicle fusion. Our data suggest that TRPM4 may play a key role in the
      control of membrane potential and electrical activity of electrically excitable
      secretory cells and the dynamic translocation of TRPM4 from a vesicular pool to
      the plasma membrane via Ca(2+)-dependent exocytosis may represent a key short-
      and midterm regulatory mechanism by which cells regulate electrical activity.

PMID- 16806466
TI  - Secretoneurin stimulates goldfish pituitary luteinizing hormone production.
AB  - Secretoneurin (SN), a 33-34 amino acid neuropeptide is derived from
      endoproteolysis of secretogranin II (SgII), a member protein of the chromogranin
      family. SN is widely distributed in various tissues of vertebrates especially in
      pituitary and hypothalamus, and is a potential new hormone. In vivo, i.p.
      injection of SN increased luteinizing hormone (LH) release in goldfish pretreated
      with the dopamine antagonist domperidone. In 6-h static incubation of goldfish
      pituitary fragments, 10 and 100 nM but not 1 nM concentrations of goldfish SN had
      a direct stimulatory effect to increase LH release by 2.3- and 1.5-fold (p<0.05),
      respectively. In addition, 500 nM SN induced a 2.6-fold increase in LHbeta
      subunit messenger RNA (mRNA) levels in pituitary fragments, regardless of whether
      LHbeta mRNA levels were expressed relative to 18S ribosomal RNA or beta-actin
      mRNA. We suggest that the stimulatory actions of SN on LH release may be a part
      of a paracrine or autocrine feedback loop in the pituitary.

PMID- 16806467
TI  - mRNA expression of MAGE-A3 gene in leukemia cells.
AB  - Leukemia-associated antigens such as proteins encoded by MAGE genes might provide
      tools for immunotherapy of leukemia. Positive and negative results of MAGE-A gene
      expression in hematological malignancies have been reported. This led us to study
      MAGE-A gene expression in human leukemias using RT-PCR. Among 115 leukemias from
      various subtypes, 14/34 (41.17%) AML were positive for one of the three genes
      analyzed (MAGE-A1 1/32; MAGE-A3 10/32; MAGE-B2 3/12). Expression was also
      detected in 23/76 (30.26%) B-cell ALL patients (MAGE-A1 2/53; MAGE-A3 20/53; MAGE
      B2 1/32). One of these patients expressed both MAGE-A1 (weak signal) and -A3
      (strong signal) genes. Other patient with CML were positive for MAGE-B2 (1/5,
      20%). MAGE-A3 expression data were corroborated by real time RT-PCR through
      determination of MAGE-A3 transcript levels. We concluded that the MAGE-A3 gene is
      expressed at the mRNA level in a proportion of human leukemias.

PMID- 16806468
TI  - Cloning and characterisation of a prophenoloxidase from the haemocytes of mud
      crab Scylla serrata.
AB  - A prophenoloxidase (proPO) cDNA was cloned from the haemocytes of mud crab Scylla
      serrata using oligonucleotide primers and RT-PCR. Both 3'- and 5'-regions were
      isolated by rapid amplification of cDNA end (RACE) method. Analysis of the
      nucleotide sequence revealed that the cDNA clone has a full length of 2663bp,
      with an open reading frame of 2019bp, a 124-bp 5'-untranslated region, and a 520
      bp 3'-untranslated region containing a poly A signal. It encodes a protein of 673
      amino acids with a predicted molecular weight of 77.5kDa and with an estimated pI
      of 5.96. It contains two putative tyrosinase copper-binding motifs with six
      histidine residues (copper A, 185, 189, 211, and copper B, 346, 350, 386). The
      proPO has thiol-ester-like motif (GCGWPQHM), which showed similar structural
      features of proPOs from other decapod crustaceans. It also contains five possible
      glycosylation sites, and a conserved C-terminal region common to all known
      proPOs. Sequence comparison showed that the proPO-deduced amino acid of mud crab
      S. serrata has an overall similarity of 78%, 57%, 56%, 51-55%, 54%, 53%, 52%,
      52%, and 52% to that of Dungeness crab Cancer magister, American lobster Homarus
      americanus, European lobster Homarus gammarus, kuruma prawn Marsupenaeus
      japonicus, crayfish Pacifastacus leniusculus, white shrimp Litopenaeus vannamei,
      tiger shrimp Penaeus monodon, green tiger shrimp Penaeus semisulcatus, and giant
      freshwater prawn Macrobrachium rosenbergii, respectively. The proPO was strongly
      expressed in haemocytes, but not in heart, eyestalk, gill, muscle, ovary,
      hepatopancreas, stomach, and intestine. The proPO transcript of mud crab S.
      serrata increased significantly in 12 and 24h post-lipopolysaccharide (LPS)
      injection, but returned to the original values in 72h post injection.

PMID- 16806469
TI  - A second generation snp-derived Escherichia coli-Streptomyces shuttle expression
      vector that is generally transferable by conjugation.
AB  - An Escherichia coli-Streptomyces shuttle vector (pJN100) was constructed, by
      inserting an origin of transfer (oriT), derived from the E. coli broad host range
      plasmid RK2, into pANT1202, a high-copy-number vector for gene expression in
      Streptomyces. The resulting conjugably transferable vector contains the pANT1202
      derived SnpR (LysR-like protein) activated snpA promoter that drives strong
      heterologous expression of proteins. We initially demonstrated that plasmid
      pJN100 was transferred with high frequency (10(-5-7) exconjugants per recipient)
      into several Streptomyces strains that were refractory to transformation by other
      means. Plasmid pJN100 was also shown to be stable in E. coli and Streptomyces. We
      confirmed functional protein expression by using a pJN100 derivative to
      complement a mutant of Streptomyces griseus with a disrupted chromosomal copy of
      the gene nonM, a gene encoding an essential reductase in the nonactin
      biosynthesis gene cluster. High levels of protein expression were confirmed using
      Western blotting to assess the production of the serine esterase NonR, an enzyme
      responsible for nonactin resistance in the nonactin producer S. griseus.

PMID- 16806470
TI  - Effects of lead contamination on soil enzymatic activities, microbial biomass,
      and rice physiological indices in soil-lead-rice (Oryza sativa L.) system.
AB  - The effect of lead (Pb) treatment on the soil enzymatic activities, soil
      microbial biomass, rice physiological indices and rice biomass were studied in a
      greenhouse pot experiment. Six levels of Pb viz. 0(CK), 100, 300, 500, 700, 900
      mg/kg soil were applied in two types of paddy soils. The results showed that Pb
      treatment had a stimulating effect on soil enzymatic activities and microbial
      biomass carbon (Cmic) at low concentration and an inhibitory influence at higher
      concentration. The degree of influence on enzymatic activities and Cmic by Pb was
      related to the clay and organic matter contents of the soils. When the Pb
      treatment was raised to the level of 500 mg/kg, ecological risk appeared both to
      soil microorganisms and plants. The results also revealed a consistent trend of
      increased chlorophyll contents and rice biomass initially, maximum at a certain
      Pb treatment, and then decreased gradually with the increase in Pb concentration.
      Pb was effective in inducing proline accumulation and its toxicity causes
      oxidative stress in rice plants. Therefore, it was concluded that soil enzymatic
      activities, Cmic and rice physiological indices, could be sensitive indicators to
      reflect environmental stress in soil-lead-rice system.

PMID- 16806471
TI  - Prisons in transition.
AB  - The role of the prison has changed, in some ways dramatically, over the last two
      decades. The prison population has grown and its composition has altered. There
      has been an increase in the depth and weight of imprisonment, and a hardening of
      its emotional tone. Prisoners' voices have been silenced, outcomes have
      deteriorated, and yet public presentation of the prison has improved. Power has
      shifted upwards, as senior managers have an unprecedented grip on establishments
      and their 'performance'. There are new fantasies about, and constructions of, the
      prison's role, with little evidence to support such public and political dreams.
      Such sleights of hand are only possible without knowledge of the prison's
      interior life. Punitive prisons which treat prisoners, and possibly prison staff,
      unfairly and with little or no respect add to human suffering and do not address
      either the problem of crime or the problem of public fear.

PMID- 16806472
TI  - Occurrence and degradation of butyltins and wastewater marker compounds in
      sediments from Barcelona harbor, Spain.
AB  - Contamination of Barcelona harbor sediments was assessed by the quantitative
      determination of butyltins (TBT, DBT and MBT) and surfactant intermediates,
      namely linear alkylbenzenes (LABs) and nonylphenols (NPs), as markers of urban
      and industrial wastewater contamination, respectively. Degradation indexes of TBT
      and LABs were calculated. Tributyltin predominated in the whole area over its
      degradation products, ranging from 98 to 4702 ng Sn/g. These elevated
      concentrations reveal a persistent historical contamination and a moderate
      degradation (BT(deg)). Moreover, the high LAB concentrations (1.2-53.1 microg/g)
      compared to the relatively low NP levels (3.8-72.0 ng/g) suggest a predominance
      of urban over industrial wastewater inputs, although a significant correlation
      (r(2) = 0.82, N = 12, P = 0.001) between LABs and NPs was found. Stormwater
      runoff and combined sewer overflows (CSO) were likely the most possible sources
      for both surfactant intermediates. The high degradation index values obtained for
      LABs could indicate an improvement in the wastewater management reducing its
      recent discharge into the Barcelona harbor area.

PMID- 16806473
TI  - Environmental contamination of heavy metals from zinc smelting areas in Hezhang
      County, western Guizhou, China.
AB  - Total heavy metal (Cd, Cr, Cu, Pb and Zn) concentrations were evaluated in
      smelting waste, soil, crop and moss samples collected from the Hezhang artisanal
      zinc smelting areas, Guizhou, China. Soil samples from the cornfield near the
      smelting sites contained extremely high Cd (5.8-74 mg kg(-1)), Pb (60-14,000 mg
      kg(-1)) and Zn (260-16,000 mg kg(-1)) concentrations. Elevated heavy metal
      concentrations were also found in corn plants and total Pb (0.80-1.5 mg kg(-1))
      and Cd (0.05-0.76 mg kg(-1)) concentrations in corn grain have totally or
      partially exceeded the national guidance limits for foodstuff. Thus, the soil-to
      crop transfer of heavy metals might pose a potential health risk to the local
      residents. Similar to the high heavy metal levels in soil and corn, Cd, Cr, Cu,
      Pb and Zn concentrations in moss samples collected from the smelting sites ranged
      from 10 to 110, 10 to 55, 26 to 51, 400 to 1200 and 330 to 1100 mg kg(-1),
      respectively, exhibiting a local spatial pattern of metals deposition from the
      atmosphere. Based on examination of Zn/Cd and Pb/Cd ratios of the analyzed
      samples, we have distinguished between the flue gas dust derived and smelting
      waste derived metals in different environmental compartments.

PMID- 16806474
TI  - Prediction of MHC-binding peptides of flexible lengths from sequence-derived
      structural and physicochemical properties.
AB  - Peptide binding to MHC is critical for antigen recognition by T-cells. To
      facilitate vaccine design, computational methods have been developed for
      predicting MHC-binding peptides, which achieve impressive prediction accuracies
      of 70-90% for binders and 40-80% for non-binders. These methods have been
      developed for peptides of fixed lengths, for a limited number of alleles, trained
      from small number of non-binders, and in some cases based straightforwardly on
      sequence. These limit prediction coverage and accuracy particularly for non
      binders. It is desirable to explore methods that predict binders of flexible
      lengths from sequence-derived physicochemical properties and trained from diverse
      sets of non-binders. This work explores support vector machines (SVM) as such a
      method for developing prediction systems of 18 MHC class I and 12 class II
      alleles by using 4208-3252 binders and 234,333-168,793 non-binders, and evaluated
      by an independent set of 545-476 binders and 110,564-84,430 non-binders. Binder
      accuracies are 86-99% for 25 and 70-80% for 5 alleles, non-binder accuracies are
      96-99% for 30 alleles. Binder accuracies are comparable and non-binder accuracies
      substantially improved against other results. Our method correctly predicts 73.3%
      of the 15 newly-published epitopes in the last 4 months of 2005. Of the 251
      recently-published HLA-A*0201 non-epitopes predicted as binders by other methods,
      63 are predicted as binders by our method. Screening of HIV-1 genome shows that,
      compared to other methods, a comparable percentage (75-100%) of its known
      epitopes is correctly predicted, while a lower percentage (0.01-5% for 24 and 5
      8% for 6 alleles) of its constituent peptides are predicted as binders. Our
      software can be accessed at .

PMID- 16806475
TI  - Apoptosis by IL-2 deprivation in human CD8+ T cell blasts predominates over death
      receptor ligation, requires Bim expression and is associated with Mcl-1 loss.
AB  - The mechanisms responsible for the down-modulation of the activation of separated
      CD4(+) or CD8(+) human T cell blasts were studied using cells obtained from
      healthy donors. In the absence of IL-2, human CD4(+) T cell blasts were sensitive
      to both FasL and Apo2L/TRAIL, but human CD8(+) T cell blasts died, with no
      additional effect of death receptor ligation. CD8(+) T cell blasts were more
      sensitive than CD4(+) T cell blasts to apoptosis induction by IL-2 deprivation,
      which was associated with a decrease in the expression of anti-apoptotic proteins
      of the Bcl-2 family, especially of Mcl-1 in CD8(+) T cell blasts. The maintenance
      of high levels of Bim expression was also necessary, since down-modulation of Bim
      expression by siRNA in normal human CD8(+) T cell blasts greatly reduced
      apoptosis by IL-2 deprivation. These data, together with previous works, point to
      an important role of the presence or absence of immuno-stimulatory cytokines in
      the type of regulation of human CD8(+) T cell responses (death by cytokine
      deprivation versus death receptor inhibition of cytokine-dependent growth).

PMID- 16806476
TI  - Saxatilin inhibits TNF-alpha-induced proliferation by suppressing AP-1-dependent
      IL-8 expression in the ovarian cancer cell line MDAH 2774.
AB  - Tumor necrosis factor-alpha (TNF-alpha)-induced proliferation of cancer cell line
      MDAH 2774 was significantly suppressed by treating the cells with saxatilin, a
      snake venom disintegrin. The suppressed proliferation was found to be associated
      with the level of interleukin-8 (IL-8) expression in the cells. TNF-alpha-induced
      IL-8 promoter activation that is inhibited by saxatilin treatment was dependent
      on activating protein-1 (AP-1) instead of nuclear factor-kappa B (NF-kappaB).
      Coexpression of dominant negative p38 (DN-p38) suggested that p38 is involved in
      the IL-8 promoter activity which is regulated by saxatilin or TNF-alpha.
      Experimental evidence clearly indicated that saxatilin inhibits TNF-alpha-induced
      proliferation of the ovarian cancer cells by suppressing IL-8 expression in AP-1
      dependent manner.

PMID- 16806477
TI  - Genome-wide survey of the gene expression response to saprolegniasis in Atlantic
      salmon.
AB  - Pathogenic saprolegniaceae species are among the major disease-causing agents in
      farmed salmonids and in freshwater fish in general. Recent studies have used high
      throughput cDNA-based methods to identify new potential actors of fish defence
      systems against various bacteria and viruses. However, the response of fish to
      fungal or fungus-like pathogens is still poorly documented. Here, we used a
      16,006-gene salmonid cDNA microarray to identify genes which transcription levels
      are modified in juvenile Atlantic salmon (Salmo salar) affected with
      saprolegniasis compared to healthy fish from the same families. Our results
      confirmed the importance of non-specific immunity in the response of fish to
      saprolegniaceae infections and identified both similarities and differences in
      their genome-wide transcriptional response to oomycetes compared with their
      responses to bacterial or viral infections. Moreover, several clones with no
      known homologues were shown to be over-transcribed in infected fish. These may
      represent as yet unidentified immune-relevant genes in fish.

PMID- 16806478
TI  - Intraocular pressure changes and ocular biometry during Sirsasana (headstand
      posture) in yoga practitioners.
AB  - PURPOSE: To study the intraocular pressure (IOP) changes in Sirsasana (headstand
      posture) done by experienced yoga practitioners and correlate the ocular
      biometric parameters with the IOP changes, and to screen for the prevalence of
      ocular hypertension in this group of subjects. DESIGN: Prospective case
      observational series. PARTICIPANTS: Seventy-five subjects (50 Asian Indians and
      25 Caucasians) from a yoga training institute volunteered for the study. METHODS:
      All participants underwent a detailed ophthalmic examination along with ocular
      biometry and corneal pachymetry. Intraocular pressure was recorded using a
      Tonopen before, during, and after the Sirsasana. Changes were compared using the
      paired t test. Age, axial length, anterior chamber depth, lens thickness, corneal
      curvature, corneal thickness, race, and the length of time for which the
      practitioner was performing yoga were correlated with the induced IOP difference
      in a randomly selected eye using Pearson's correlation coefficient with
      Bonferroni correction for multiple comparisons. MAIN OUTCOME MEASURES: Ocular
      biometry and induced IOP difference. RESULTS: The mean increase in IOP at
      baseline and immediately after assuming Sirsasana was 15.1+/-4.1 mmHg (R = 0.07;
      P = 0.999) and after 5 minutes was 15.8+/-4.6 mmHg (R = -0.25; P = 0.357). The
      induced increase in IOP during the posture was twice the baseline IOP. There was
      no correlation between age, ocular biometry, and ultrasound pachymetry when
      compared with the induced IOP difference. One subject (1.33%) was found to have
      baseline IOP of more than 21 mmHg. CONCLUSION: There was a uniform 2-fold
      increase in the IOP during Sirsasana, which was maintained during the posture in
      all age groups irrespective of the ocular biometry and ultrasound pachymetry. We
      did not demonstrate a higher prevalence of ocular hypertensives in this cohort of
      yoga practitioners nor did the risk factors contributing to glaucoma show any
      correlation with magnitude of IOP raise during the posture.

PMID- 16806479
TI  - Acquired dyschromatopsia among petrochemical industry workers exposed to benzene.
AB  - Exposure to organic solvents, which are widely used in industry, can lead to
      dysfunction of the nervous system. However, controversy continues about the
      nature of early-stage damage to the nervous system from low-grade chronic
      exposure to organic solvents. Since loss of color-vision can be a sensitive early
      marker of neurotoxic damage, the main aim of this study was to investigate the
      association between low-level chronic exposure to organic solvents, especially
      benzene, and acquired dyschromatopsia. The study initially comprised 1236 workers
      who were employed at a large petrochemical distillation factory. After excluding
      those workers who may have had color-vision impairment due to congenital or
      acquired eye diseases and those with other medical conditions, 908 males who had
      worked for at least 6 months were included in the final analysis. Those who
      worked only in the office were categorized as nonexposed, while those who worked
      at outside facilities were divided into three groups of approximately equal size
      according to their estimated cumulative exposure levels to benzene (low, medium,
      high). Color-vision was assessed using the Lanthony D-15 desaturated panel color
      test. The results showed that the color-confusion index (CCI) was positively
      related to age. In the qualitative assessment of types of color-vision loss, the
      prevalence of total dyschromatopsia was significantly higher with increasing
      cumulative exposure levels in the left eye (p<0.05) but not in the right eye. The
      significance for the prevalence of type III dyschromatopsia was borderline in the
      left eye (p=0.0571). The relationship between acquired dyschromatopsia and
      exposure level also showed an increase in the odds ratio in the left eye but not
      in the right eye. Taken together, these results suggest that chronic low-level
      exposure to benzene can lead to acquired dyschromatopsia.

PMID- 16806480
TI  - Benchmark concentrations for methyl mercury obtained from the 9-year follow-up of
      the Seychelles Child Development Study.
AB  - Methyl mercury (MeHg) is highly toxic to the developing nervous system. Human
      exposure is mainly from fish consumption since small amounts are present in all
      fish. Findings of developmental neurotoxicity following high-level prenatal
      exposure to MeHg raised the question of whether children whose mothers consumed
      fish contaminated with background levels during pregnancy are at an increased
      risk of impaired neurological function. Benchmark doses determined from studies
      in New Zealand, and the Faroese and Seychelles Islands indicate that a level of 4
      25 parts per million (ppm) measured in maternal hair may carry a risk to the
      infant. However, there are numerous sources of uncertainty that could affect the
      derivation of benchmark doses, and it is crucial to continue to investigate the
      most appropriate derivation of safe consumption levels. Earlier, we published the
      findings from benchmark analyses applied to the data collected on the Seychelles
      main cohort at the 66-month follow-up period. Here, we expand on the main cohort
      analyses by determining the benchmark doses (BMD) of MeHg level in maternal hair
      based on 643 Seychellois children for whom 26 different neurobehavioral endpoints
      were measured at 9 years of age. Dose-response models applied to these continuous
      endpoints incorporated a variety of covariates and included the k-power model,
      the Weibull model, and the logistic model. The average 95% lower confidence limit
      of the BMD (BMDL) across all 26 endpoints varied from 20.1 ppm (range=17.2-22.5)
      for the logistic model to 20.4 ppm (range=17.9-23.0) for the k-power model. These
      estimates are somewhat lower than those obtained after 66 months of follow-up.
      The Seychelles Child Development Study continues to provide a firm scientific
      basis for the derivation of safe levels of MeHg consumption.

PMID- 16806481
TI  - Interpretation of small effect sizes in occupational and environmental
      neurotoxicology: individual versus population risk.
AB  - Some have questioned the importance of the small effect sizes generally reported
      in epidemiological studies of neurotoxicity. To some extent, this reflects a
      failure to appreciate the critical distinction between individual and population
      risk. In the first part of the paper, arguments are marshaled to support the
      contention that small shifts in the mean value of a health index within a study
      sample can, under some circumstances, carry substantial implications for the
      health status of the population from which the study sample was drawn. Under such
      circumstances, a population-based approach to prevention might be as effective as
      a patient-based approach. The second part clarifies conditions under which this
      will be true (e.g., a monotonic relationship between a health index and risk of
      disease) and conditions under which it might not (e.g., a J-shaped relationship).
      In the third part, the relative levels of uncertainty in characterizing
      individual versus population risk are explored. In neurotoxicological studies,
      uncertainty in characterizing individual risk could be reduced by adjusting, in
      addition to bone fide confounders, for covariates that are strong predictors of
      outcome and by more assiduous efforts to characterize major effect modifiers.

PMID- 16806482
TI  - Cisplatin mediates selective downstream hydrolytic cleavage of Met-(Gly)(n)-His
      segments (n=1,2) in methionine- and histidine-containing peptides: the role of
      ammine loss trans to the initial Pt-S(Met) anchor in facilitating amide
      hydrolysis.
AB  - The pH- and time-dependent reactions of the antitumor drug cisplatin, cis
      [PtCl(2)(NH(3))(2)], with the methionine- and histidine-containing pentapeptides
      Ac-Met-Gly-His-Gly-Gly-OH, Ac-Met-Gly-Gly-His-Gly-OH and Ac-Gly-Met-Gly-His-Gly
      OH (Gly=glycyl, Met=L-methionyl, His=L-histidyl) at 313K have been investigated
      by high performance liquid chromatography, mass spectrometry and nuclear magnetic
      resonance. Cisplatin mediates a rapid "downstream" hydrolytic cleavage of the Met
      Gly amide bond in weakly acid solution (pH < or =5) for all three peptides,
      leading to release of H-Gly-His-Gly-Gly-OH, H-Gly-Gly-His-Gly-OH and H-Gly-His
      Gly-OH, respectively, and formation of kappa(2)S,N(M) chelate complexes of the
      methionine-containing residuals Ac-Met-OH or Ac-Gly-Met-OH. An alternative
      reaction pathway affords tridentate kappa(3)S,N(M),N(imidazole) macrochelates of
      the original pentapeptide following ammine loss. The downstream cleavage pathway
      is competitive with the likewise cisplatin-mediated upstream cleavage of the Ac
      Gly linkage in the pentapeptide Ac-Gly-Met-Gly-His-Gly-OH. This leads to
      formation of both the kappa(3)S,N(M),N(G1) complex of H-Gly-Met-Gly-His-Gly-OH
      due to upstream cleavage and the analogous tridentate complex for H-Gly-Met-OH
      due to initial downstream loss of H-Gly-His-Gly-OH followed by upstream loss of
      acetic acid. As downstream cleavage is not observed for Ac-(Gly)(2)-Met-(Gly)(2)
      OH under similar conditions, it may be concluded that rapid histidine imidazole
      substitution of the ammine ligand in trans-position to an anchoring methionine S
      atom must assist hydrolytic cleavage of the Met-Gly amide bond.

PMID- 16806483
TI  - Crystal structure of ferric-yersiniabactin, a virulence factor of Yersinia
      pestis.
AB  - Yersiniabactin (Ybt), the siderophore produced by Yersinia pestis, has been
      crystallized successfully in the ferric complex form and the crystal structure
      has been determined. The crystals are orthorhombic with a space group of
      P2(1)2(1)2(1) and four distinct molecules per unit cell with cell dimensions of
      a=11.3271(+/-0.0003)A, b=22.3556(+/-0.0006)A, and c=39.8991(+/-0.0011)A. The
      crystal structure of ferric Ybt shows that the ferric ion is coordinated as a 1:1
      complex by three nitrogen electron pairs and three negatively charged oxygen
      atoms with a distorted octahedral coordination. The molecule displays a Delta
      absolute configuration with chiral centers at N2, C9, C10, C12, C13, and C19 in
      R, R, R, R, S, S configurations, respectively. Few of the crystal structures of
      siderophores have been solved, and those which have been are of simple
      hydroxamate and catechol types such as ferrioxamine B and agrobactin. To our
      knowledge this is the first report of the ferric crystal structure of 5-member
      heterocycle siderophore.

PMID- 16806484
TI  - Toxoplasmosis following alemtuzumab based allogeneic haematopoietic stem cell
      transplantation.
AB  - Alemtuzumab is a humanised monoclonal antibody against CD52 used as an
      immunosuppressive agent in allogeneic HSCT. Regimens including alemtuzumab for
      allogeneic haematopoietic stem cell transplant (HSCT) conditioning have been
      associated with an increased incidence of viral complications. Patients with
      prior toxoplasma exposure undergoing alemtuzumab containing HSCT could therefore
      be expected to be at a higher risk of toxoplasma reactivation. We conducted a
      retrospective review of 220 alemtuzumab based allogeneic HSCT performed over a 4
      year period, of which 202 were reduced intensity conditioning (RIC) HSCT. A total
      of 67 patients (30%) in whom the pre-transplant recipient toxoplasma IgG test was
      positive were classified as high-risk for toxoplasma infection. All patients
      started trimethoprim/sulfamethoxazole prophylaxis following HSCT when the
      neutrophil count was > or = 1x10(9)/l. Two high-risk patients developed
      toxoplasma invasive disease with cerebral involvement at 2 and 4 months post
      transplantation respectively. The incidence of toxoplasma disease in the entire
      cohort and amongst high-risk patients was 0.9% and 3.0% respectively. Despite in
      vivo T-cell depletion with alemtuzumab, the incidence of toxoplasma disease in
      our cohort was comparable with previously reported T-cell replete HSCT studies.

PMID- 16806485
TI  - The surface expression of HLA-F on decidual trophoblasts increases from mid to
      term gestation.
AB  - HLA-F has recently only begun to be studied in earnest, and has been thought not
      to be expressed on the cell surface. However, in our previous report, we
      demonstrated surface expression of HLA-F on extravillous trophoblasts (EVTs)
      invading the decidua in term placental tissues. To better understand its
      function, we attempted to determine when surface expression of HLA-F begins
      during normal pregnancy, and whether there is a difference in expression between
      normal and preeclamptic placentas, by comparing the expression of HLA-G and -E by
      immunohistochemical staining with anti-HLA-E, -F and -G antibodies (3D12, 3D11
      and 87G, respectively). In EVTs, HLA-F was expressed only in the cytoplasm weakly
      during the first trimester, after which expression increased and moved to the
      cell surface with the progression of pregnancy from the second trimester, which
      was confirmed by the results of double-labeled immunofluorescence staining with
      anti-HLA-F and anti-HLA-G antibodies, and by flow cytometry using trophoblasts
      isolated from the decidua. HLA-E showed similar expression as HLA-F, though it
      was expressed on the cell surface from the first trimester, while HLA-G was
      expressed strongly in the cytoplasm and on the cell surface during all stages of
      pregnancy. The expressions of HLA-E, -F and -G in preeclamptic placentas were not
      different from those in normal placentas, though there were a greater number of
      necrotic EVTs in preeclampsia. The increase in expression of HLA-E and HLA-F from
      the second trimester to full term was coincident with the timing of rapid growth
      of the fetus. Our results suggest that these may function together to prepare an
      environment that supports fetal growth.

PMID- 16806486
TI  - Regulation of chemokine production in response to pro-inflammatory cytokines in
      first trimester decidual cells.
AB  - OBJECTIVE: Chemokines initiate the immune response by controlling leukocyte
      migration and lymphocyte development. Macrophage infiltration of the decidua has
      been implicated in the genesis of recurrent miscarriage and preeclampsia.
      Therefore, we determined whether cultured human decidual cells produce
      monocyte/macrophage-recruiting chemokines in response to a potent pro
      inflammatory cytokine, interleukin-1beta (IL-1beta), and whether decidual cell
      conditioned medium contains monocyte- and macrophage-chemoattractant activity.
      METHODS: Leukocyte-free first trimester decidual cells were treated for 6h with
      estradiol (E(2)) and medroxyprogesterone acetate (MPA) to mimic the steroidal
      milieu of pregnancy, or E(2) and MPA and IL-1beta (1 ng/ml) to mimic inflamed
      decidua. Total RNA was used for cDNA synthesis. Biotinylated cRNAs were generated
      and chemically fragmented for hybridization on Affymetrix HG_U133 Plus 2.0 chips
      followed by fluorescence labeling and optical scanning. Raw data generated from
      Affymetrix GCOS 1.2 (GeneChip Operating Software) were analyzed by GeneSpring 7.2
      software. Subsequently microarray results were validated by real time RT-PCR and
      Western blotting. A functional study of monocyte migration was carried out also
      using conditioned media from culture. RESULTS: Five chemokines responsible for
      monocyte/macrophage chemoattraction and activation, including C-C motif ligand 2
      (CCL2), CCL5, C-X-C motif ligand 2 (CXCL2), CXCL3 and CXCL8, were markedly
      elevated from 29- to 975-fold after exposure to IL-1beta in cultured first
      trimester decidual cells. The results of real-time RT-PCR (up-regulation from 43-
      to 3069-fold) and Western blotting (up-regulation from 15- to 300-fold) confirmed
      the microarray findings. Monocyte migration was significantly induced by the
      conditioned medium from IL-1beta-treated decidual cells. CONCLUSIONS: Treatment
      of first trimester decidual cells with IL-1beta induces secretion of
      monocyte/macrophage recruiting-chemokines and promotes monocyte migration.
      Extrapolation of these in vitro results to the milieu of implantation site
      suggests a mechanism whereby IL-1beta could mediate excessive macrophage
      infiltration of the decidua.

PMID- 16806487
TI  - Myeloid-related protein-8/14 is associated with proinflammatory cytokines in
      cervical mucus.
AB  - Myeloid-related protein-8 (MRP-8), MRP-14, and MRP-8/14 are found in a variety of
      inflammatory conditions and are involved in the host defense system. The
      objective of this study was to determine the concentrations of MRP-8, MRP-14, and
      MRP-8/14 in human cervical mucus and the associations between MRP-8/14 and
      proinflammatory cytokines. Samples of cervical mucus were obtained using a
      syringe from sexually active women (n=97) during the preovulatory phase. Samples
      from seven women were obtained using a swab placed in the cervical canal during
      the proliferative, preovulatory, and luteal phases. Concentrations of MRP-8, MRP
      14, MRP-8/14, IL-1alpha, IL-6, IL-8, and granulocyte elastase were measured using
      an ELISA. The mean levels of MRP-8, MRP-14, and MRP-8/14 in cervical mucus were
      1.87, 0.46, and 23.90microg/ml, respectively. The concentration of MRP-8/14
      showed positive correlations with concentrations of IL-1alpha (p<0.0001), IL-8
      (p<0.0001), and granulocyte elastase (p<0.0001). However, there were no
      significant differences in MRP-8/14 levels in the cervical mucus of each patient
      during the menstrual cycle. MRP-8/14 was mainly detected in human cervical mucus
      and showed a positive correlation with proinflammatory cytokines. The MRP-8/14
      level in cervical mucus may be useful as a marker of inflammation of the uterine
      cervix.

PMID- 16806488
TI  - Analysis of endometrial myeloid and lymphoid dendritic cells during mouse estrous
      cycle.
AB  - This study was performed to evaluate the frequency and localization of
      endometrial myeloid (CD11c(+) CD11b(+)) and lymphoid (CD11c(+) CD8alpha(+))
      dendritic cells (DCs) at different stages of murine estrous cycle. To address the
      systemic effect of ovarian hormones fluctuations during estrous cycle, the same
      variables were studied in splenic DCs as well. Stages of the estrous cycle of
      Balb/c mice were determined by examination of vaginal smears. Frozen sections of
      uterus and spleen at each stage of estrous cycle were stained for CD11c and MHC
      II. Two-color immunohistochemistry was also carried out using anti-CD11c with one
      of the antibodies against CD11b, CD8alpha, CD86, and DEC-205. The average density
      of DCs and relative percentage of myeloid and lymphoid DCs (MDCs and LDCs) were
      determined at each stage of estrous cycle by morphometric analysis. Our results
      showed that DCs were present throughout the estrous cycle in mice endometrium,
      but their frequency was highest at estrus and lowest at proestrus (P<0.005). The
      lymphoid subset of DCs was more prominent at estrus relative to those at other
      stages (P<0.005). Conversely, the relative percentage of myeloid DCs at estrus
      was significantly lower compared to other stages (P<0.005). Nearly all
      endometrial and splenic DCs expressed CD86 and MHC-II. At proestrus, and
      particularly at estrus, DCs were more concentrated subadjacent to the luminal and
      glandular epithelial layers with some scattered throughout the stroma whereas, at
      metestrus and diestrus, DCs were randomly distributed in stroma and around the
      glandular and luminal epithelial layers. The number and immunophenotype of
      splenic DCs were not statistically different between stages of estrous cycle. Our
      results suggest that endometrial but not splenic myeloid and lymphoid DCs are
      influenced by steroid hormones during estrous cycle.

PMID- 16806489
TI  - Association between aggressiveness, schizotypal personality traits and cannabis
      use in Swiss psychology students.
AB  - Associations between aggressiveness, schizotypal traits, and self-declared
      cannabis consumption were explored in Swiss psychology students (n = 205). Higher
      hostility levels were strongly associated with more pronounced schizotypal
      traits, whereas frequency of cannabis use was not. Therefore, earlier reported
      correlations might be due to a subgroup of hostile consumers.

PMID- 16806490
TI  - Episodic memory for emotional and non-emotional words in individuals with
      anhedonia.
AB  - Anhedonia is a symptom that plays a significant role in theories of illness such
      as depression and schizophrenia. Some previous research suggests that
      participants who report high levels of social/physical anhedonia also show
      deficits in both self-report and physiological measures of emotional processing,
      particularly for measures of emotional valence as compared with emotional
      arousal. Little is known about memory for emotionally valenced information or how
      this might be related to emotional processing in anhedonia. Participants were 391
      undergraduate students participating for course credit. We administered an
      incidental encoding task that required participants to rate emotional words on
      both valence and arousal dimensions. We then administered surprise recall and
      recognition tasks to all participants. Results indicated that higher levels of
      physical and social anhedonia were associated with attenuated valence ratings of
      emotional words but did not influence arousal ratings or the memory pattern for
      emotionally valenced information. These findings suggest that there is some
      reduction in emotional experience in individuals with anhedonia, but that this
      reduction does not appear to produce a deficit in memory performance, perhaps due
      to the intact experience of arousal.

PMID- 16806491
TI  - Neutrophil extracellular trap formation by bovine neutrophils is not inhibited by
      milk.
AB  - Neutrophils are the first line of defense in a mammary gland infection. However,
      the process of neutrophil transmigration across a membrane and ingestion of fat
      and/or casein when incubated in milk have been shown to inhibit bacterial
      phagocytosis and oxidative burst functions. Recently, a killing mechanism has
      been described whereby stimulated neutrophils release nuclear and granule
      material in fibrous webs that physically trap and kill bacteria. We demonstrate
      that these neutrophil extracellular traps are also produced by bovine blood
      neutrophils stimulated with PMA/ionomycin. Importantly, neutrophil extracellular
      traps can be formed when neutrophils have been incubated for up to 6h in milk
      prior to stimulation. This contrasts milk's rapid inhibition of bacterial
      phagocytosis and oxidative burst functions in the neutrophil. Furthermore,
      stimulation of neutrophils with bacteria common to mammary gland infections leads
      to neutrophil extracellular traps being formed in milk. Some bacteria tested
      stimulated enhanced formation of neutrophil extracellular traps in milk compared
      to culture media. Therefore, being unaffected by incubation in milk may indicate
      an important role for neutrophil extracellular traps in defense against mastitis.

PMID- 16806492
TI  - Assessment of the ovine acute phase response and hepatic gene expression in
      response to Escherichia coli endotoxin.
AB  - Lipopolysaccharide (LPS), a bacterial membrane endotoxin, induces a systemic
      inflammatory response (IFR) through the activation of blood monocytes and hepatic
      kupffer cells. These cells secrete pro-inflammatory cytokines, which subsequently
      activate the hypothalamic-pituitary-adrenal axis (HPAA) to release cortisol, an
      anti-inflammatory hormone that regulates the IFR and subsequent immune response
      (IR). The intent of this study was to characterize the acute phase response in
      female sheep challenged systemically with a range of doses of Escherichia coli
      endotoxin. Yearling ewes were challenged with an i.v. bolus dose of LPS (0, 200,
      400, 600 ng/kg BW) and the acute phase response assessed by measuring serum
      interleukin (IL)-6 and cortisol concentrations, and the febrile response over
      time. A follow-up liver biopsy study was performed to determine kinetic
      differences in the expression of eight candidate hepatic genes between LPS dose
      groups using real-time RT-PCR. The initial time trail did not follow a linear
      dose response relationship with respect to the febrile and HPAA response to LPS
      challenge. Serum IL-6 concentrations increased in the two highest treatment
      groups but did not correlate with the observed febrile and HPAA response. The
      expression of Toll-like receptor 4, CD14, IL-6, tumor necrosis factor-alpha, IL
      1beta, macrophage migration inhibitory factor, 11-beta-hydroxysteroid
      dehydrogenase (HSD), and tachykinin precursor 1 hepatic genes was dependent on
      both the dose and the kinetics of the response to LPS.

PMID- 16806493
TI  - Dietary antioxidants and behavioral enrichment enhance neutrophil phagocytosis in
      geriatric Beagles.
AB  - The study objective was to determine the effects of feeding food enriched in
      antioxidants and a program of environmental/cognitive enrichment on selected ex
      vivo assays of inflammatory and immune cells in healthy geriatric Beagle dogs
      (n=21). Four groups of dogs were tested using a 2 x 2 factorial design. The 2
      year longitudinal study included both nutritional (control food or antioxidant
      fortified food) and behavioral (normal level or cognitive enrichment)
      interventions. Behavior enrichment included increased exercise, environmental
      enrichment, and a series of learning tasks. Phagocytosis of opsonized latex
      coated beads by peripheral blood neutrophils was measured by flow cytometry and
      found to be significantly increased in dogs receiving both dietary antioxidants
      and cognitive enrichment. Simultaneous stimulation of cells with Con A and
      suppression with Dex resulted in decreased lymphocyte proliferation in dogs
      receiving both dietary antioxidants and cognitive enrichment, compared to dogs
      receiving dietary antioxidants or cognitive enrichment alone. There were no
      significant differences between the groups of dogs for percentages of CD4 and CD8
      T-lymphocyte subpopulations before or after lymphocyte stimulation with Con A.
      These results support our hypothesis that both dietary antioxidants and
      behavioral enrichment enhance host defense mechanisms.

PMID- 16806494
TI  - The molecular cloning and functional expression of the dog CCR5.
AB  - Activation of CCR5 by specific chemokines is involved in the regulation of the
      immunological response of leukocytes at sites of inflammation. In addition, CCR5
      serves as a fusion co-factor for macrophage-tropic strains of human
      immunodeficiency virus type 1 (HIV-1). Consequently, several CCR5 antagonists are
      currently in development for the treatment of HIV-1 infection. The dog CCR5 gene
      was cloned in order to characterise the chemokine binding site of the dog
      receptor for comparison across species. The deduced amino acid sequence of the
      dog CCR5 has close homology to the human receptor (80% identity). A HEK-293 cell
      line expressing the dog recombinant receptor was generated and immunoblot
      analysis with an anti-human CCR5 antibody revealed a 58kDa band in the cell
      lysate. In functional calcium signalling assays, the CCR5 endogenous ligands MIP
      1alpha, MIP-1beta and RANTES evoked a robust response in the dog recombinant CCR5
      cells. In a CRE-Luc (cAMP response element-luciferase) reporter gene assay, MIP
      1beta (0.01-30nM) produced concentration-dependent inhibition of forskolin
      induced elevation in cAMP levels, and was equipotent in dog, human and macaque
      recombinant CCR5 cells (EC(50) 0.4, 0.21 and 0.47nM, respectively). These data
      suggest that chemokine signalling is conserved in the dog CCR5.

PMID- 16806495
TI  - Expression of different classes of immunoglobulin in intraepithelial plasma cells
      of the Harderian gland of domestic ducks Anas platyrhynchos.
AB  - The Harderian gland of chickens contains numerous plasma cells and is considered
      as a peripheral lymphoid organ. Data about this gland in other avian species are
      scarce or inexistent. Considering that ducks show some unique characteristics
      regarding the immune system, which are important in evolutionary context, and
      that unusual location of plasma cells into the epithelium was recently described
      in primitive avian species, here we investigated the occurrence and characterized
      intraepithelial plasma cells in the Harderian gland of ducks, according to the
      immunoglobulin produced. Numerous intraepithelial plasma cells were found
      confined to the Harderian gland ducts. Plasma cells were also found in the ducts
      lamina propria. IgM-positive cells were the most abundant into the epithelium. In
      contrast, IgY- or IgA-positive cells were predominant in the lamina propria. The
      constancy of intraepithelial plasma cells in all specimens examined indicates
      that they may be essential mediator for an effective immunesurvaillance of the
      ocular mucosa.

PMID- 16806496
TI  - Modulation of acute graft-versus-host disease and chimerism after adoptive
      transfer of in vitro-expanded invariant Valpha14 natural killer T cells.
AB  - Mouse natural killer T cells with an invariant Valpha14-Jalpha18 TCR
      rearrangement (Valpha14i NKT cells) are able to regulate immune responses through
      rapid and large amounts of Th1 and Th2 cytokine production. It has been reported
      that in vivo administration of the Valpha14i NKT cell ligand, alpha
      galactosylceramide (alpha-GalCer) significantly reduced morbidity and mortality
      of acute graft-versus-host disease (GVHD) in mice. In this study, we examined
      whether adoptive transfer of in vitro-expanded Valpha14i NKT cells using alpha
      GalCer and IL-2 could modulate acute GVHD in the transplantation of spleen cells
      of C57BL/6 mice into (B6xDBA/2) F(1) mice. We found that the adoptive transfer of
      cultured spleen cells with a combination of alpha-GalCer and IL-2, which
      contained many Valpha14i NKT cells, modulated acute GVHD by exhibiting long-term
      mixed chimerism and reducing liver damage. Subsequently, the transfer of
      Valpha14i NKT cells purified from spleen cells cultured with alpha-GalCer and IL
      2 also inhibited acute GVHD. This inhibition of acute GVHD by Valpha14i NKT cells
      was blocked by anti-IL-4 but not by anti-IFN-gamma monoclonal antibody.
      Therefore, the inhibition was dependent on IL-4 production by Valpha14i NKT
      cells. Our findings highlight the therapeutic potential of in vitro-expanded
      Valpha14i NKT cells for the prevention of acute GVHD after allogeneic
      hematopoietic stem cell transplantation.

PMID- 16806497
TI  - PACAP 38 as a modulator of immune and endocrine responses during LPS-induced
      acute inflammation in rats.
AB  - The effect of PACAP 38 administration on neuroendocrine and immune parameters was
      examined in rats with LPS-induced peritonitis. Treatment with PACAP 38 alone did
      not influence the serum level of the cytokines and hormones examined, but
      significantly decreased immune cell activity. When administered together with
      LPS, PACAP 38 reversed its effect on immune and humoral parameters, causing a
      decrease in the serum concentrations of TNFalpha and corticosterone, and an
      increase in T4 and GH. The majority of PACAP 38 effects disappeared earlier than
      those previously observed for VIP. PACAP 38 appears to represent a short-lasting
      modulator of immune and endocrine responses during acute inflammation.

PMID- 16806498
TI  - Elevated serum soluble vascular adhesion protein-1 (VAP-1) in patients with
      active relapsing remitting multiple sclerosis.
AB  - Vascular adhesion protein-1 (VAP-1) is an endothelial cell molecule which
      controls leukocyte infiltration into tissues. Elevated serum soluble VAP-1-levels
      have been described in certain diseases with an inflammatory component. VAP-1
      expression or function has not previously been studied in multiple sclerosis
      (MS). We report here that the concentration of soluble VAP-1 in serum is
      significantly higher in multiple sclerosis patients with ongoing inflammatory
      activity, as demonstrated by gadolinium-enhancing MRI lesions, when compared to
      patients with no gadolinium-enhancing lesions (555+/-195 vs. 388+/-102 ng/ml,
      p=0.0068). We propose that VAP-1 might participate in controlling leukocyte entry
      into inflamed brain.

PMID- 16806499
TI  - Isolation and culture of microvascular endothelial cells from murine spinal cord.
AB  - The isolation and culture of spinal cord microvascular endothelial cells (SCMEC),
      which form the blood-spinal cord barrier (BSCB), is described. Though
      morphologically similar to brain microvascular endothelial cells (BMEC) that form
      the blood-brain barrier (BBB), SCMEC express reduced amounts of several prominent
      BBB proteins, including tight junction-associated proteins ZO-1 and occludin,
      adherens junction-associated proteins beta-catenin and VE-cadherin, and the
      efflux transporter P-glycoprotein. These distinguishing features may reflect more
      widespread differences between the BBB and BSCB that impact physiological and
      pathophysiological processes.

PMID- 16806500
TI  - Serial blood T cell repertoire alterations in multiple sclerosis patients;
      correlation with clinical and MRI parameters.
AB  - A significant skewing of the peripheral T cell repertoire has been shown in
      relapsing-remitting multiple sclerosis (MS). Most of the studies already
      performed in this field are cross-sectional and therefore, little is known of the
      T cell repertoire evolution over time in MS and the correlation of T cell
      repertoire variation with clinical and MRI parameters. This study was performed
      on serially harvested frozen PBMC from nine untreated MS patients (27 samples)
      and 14 healthy individuals. The blood T cell repertoire of each patient was
      analysed at the complementarity determining region 3 (CDR3) level and compared
      with a monthly MRI scan performed over a six month period with assessment of T2
      lesion load and gadolinium enhancing lesions. A highly significant blood T cell
      repertoire skewing was observed in MS patients as compared with healthy controls
      (p<0.01). In addition, the number of altered Vbeta families correlated
      significantly with both the T2 lesion volume and the number of gadolinium
      enhancing lesions as assessed by MRI (Spearman correlation tests, r=0.51 and
      r=0.44, p<0.01 and p<0.05 respectively). Furthermore, the variation of the number
      of altered Vbeta families over time also correlated with the appearance of new
      gadolinium enhancing lesions (r=0.36, p=0.05). These findings which need
      confirmation on larger serial cohorts, suggest an association between the
      magnitude of TCRBV CDR3 length distribution alterations in the peripheral blood
      of MS patients and the disease process.

PMID- 16806501
TI  - Measuring health-related quality of life after pediatric cochlear implantation: a
      systematic review.
AB  - OBJECTIVE: The measurement of health-related quality of life (HRQL) in children
      presents conceptual and methodological challenges owing to the
      multidimensionality of the required information and limitations in patient self
      report. HRQL results provide a broad measure of treatment impact from the patient
      and family perspective and are crucial to guiding clinical and policy decisions.
      The objective of this study was to evaluate how HRQL in children with cochlear
      implants has been measured in published studies in order to draw conclusions that
      could inform future investigations of this area of clinical research. METHODS: We
      searched PubMed, EMBASE, CINAHL, PsychoInfo, and Web of Science databases using a
      defined search string and hand-searched reference lists of relevant articles and
      personal files. Retrieved citations were reviewed in two stages, a title and
      abstract screen followed by review of the full-length article. Inclusion criteria
      for studies were: (1) original peer-reviewed research article; (2) enrolled
      subjects <18 years old with cochlear implants; (3) use of a HRQL instrument that
      incorporated components of physical, mental, and social health; and (4) in
      English. Data from full-length articles were extracted by a single-investigator.
      RESULTS: We retrieved 671 citations with our search strategy, and 10 citations
      were found to be eligible for inclusion. All studies used a cross-sectional
      design, and three types of HRQL instruments were used: generic questionnaires, ad
      hoc instruments designed specifically for the purposes of the study, and the
      parents views and experiences with pediatric CI questionnaire. Heterogeneity in
      study design and instruments prevented a quantitative, meta-analysis of the data.
      CONCLUSIONS: Studies that used well-validated, generic HRQL instruments supported
      conclusions that were less subject to potential bias from the perspective of the
      clinician investigator. Most studies did not use well-defined cohorts with
      respect to age at implantation and duration of implant use, and conclusions in
      these studies were also subject to potential bias. No well-validated, deafness
      specific HRQL instruments are currently available. Future research should be done
      with existing, generic HRQL instruments and with strict study inclusion criteria.
      Suggested generic HRQL instruments are discussed.

PMID- 16806502
TI  - Epstein-Barr virus integrates frequently into chromosome 4q, 2q, 1q and 7q of
      Burkitt's lymphoma cell line (Raji).
AB  - Epstein-Barr virus (EBV) integration into a Burkitt's lymphoma (BL) cell line
      (Raji) was investigated, using polymerase chain reaction (PCR), Southern
      hybridization, genomic library screening and fluorescence in situ hybridization
      (FISH). BaMHIW fragments of the EBV genome and DNA sequences of the viral latent
      membrane protein (LMP)1 and LMP2 genes were detected in Raji cells. BaMHI
      digested high-molecular weight DNA from Raji cells generated 4 and 10 kb, 23 kb
      fragments that hybridized to Probe-1 (EBV genome 13232-16189) and Probe-2 (EBV
      genome 5-3271). Genomic library for Raji cells was constructed. Plaques (1 x
      10(5)) were screened with Probe-2, and four positive clones were obtained.
      Chromosomal integration of EBV DNA was detected in the Raji cell. The viral
      integration sites included 1p, 1q, 2q, 3p, 3q, 4q, 5q, 6q, 7p, 7q, 9q, 11p, 14q
      and 15q. Despite this multiplicity of integration sites, integration showed high
      frequency only at the sites 4q, 2q, 1q and 7q; 64% of the total signals were
      found in these four chromosomal bands. No viral integration occurred in
      chromosomes 16-22 or the sex chromosomes (X, Y). This study is the first
      comprehensive FISH analysis of EBV integration into the chromosomes of the Raji
      cell line. The findings support the notion that EBV integrates into the Raji cell
      genome non-randomly.

PMID- 16806503
TI  - A universal heterologous internal control system for duplex real-time RT-PCR
      assays used in a detection system for pestiviruses.
AB  - A heterologous in vitro transcript based on a specific primer-probe HEX system
      was generated as a universal internal control (IC) to improve virus-specific real
      time reverse-transcriptase PCR (RT-PCR) assays. By using a set of different
      primers, several PCR fragments of desired sizes of an in vitro transcript of the
      enhanced green fluorescent protein (EGFP) gene were generated, and the fragments
      were detected using a HEX-labelled probe. For long-term storage of the in vitro
      transcript a special RNA-safe buffer (RSB) was developed. Freezing and thawing of
      the IC diluted in RSB did not result in any substantial loss of detectable IC
      copy numbers. The new IC system was used for the first time in a duplex real-time
      RT-PCR assay for the detection of pestivirus-derived RNA, in particular from
      bovine viral diarrhea virus (BVDV). Primers and TaqMan probes for the 'panpesti'
      assay were selected by analysing the consensus sequence of the 5' non-translated
      region (5' NTR) of more than 600 different pestiviruses. Finally, the optimised
      primer probe combination showed an analytical sensitivity of less than 10
      copies/reaction. In the duplex set-up, the analytical sensitivity of the
      validated real-time RT-PCR was identical to the sensitivity of the single assay
      without IC, and the diagnostic sensitivity of the duplex assay was equal or
      higher if compared to virus isolation.

PMID- 16806504
TI  - Evaluation of a commercial enzyme immunoassay for the detection of norovirus
      antigen in fecal samples from children with sporadic acute gastroenteritis.
AB  - The Ridascreen Norwalk-like virus enzyme immunoassay was compared with (RT)-PCR
      on 92 stool samples collected from children with sporadic acute gastroenteritis.
      Homogenization and pre-dilution of the whole stool sample resulted in high
      specificity (97.5%) and moderate sensitivity (60%). This assay may be useful to
      screen outbreaks for norovirus, but limited to detect the virus in sporadic cases
      of diarrhea.

PMID- 16806505
TI  - Autism, the superior temporal sulcus and social perception.
AB  - The most common clinical sign of autism spectrum disorders (ASD) is social
      interaction impairment, which is associated with communication deficits and
      stereotyped behaviors. Based on recent brain-imaging results, our hypothesis is
      that abnormalities in the superior temporal sulcus (STS) are highly implicated in
      ASD. STS abnormalities are characterized by decreased gray matter concentration,
      rest hypoperfusion and abnormal activation during social tasks. STS anatomical
      and functional anomalies occurring during early brain development could
      constitute the first step in the cascade of neural dysfunction underlying ASD. We
      will focus this review on the STS, which has been highly implicated in social
      cognition. We will review recent data on the contribution of the STS to normal
      social cognition and review brain-imaging data implicating this area in ASD. This
      review is part of the INMED/TINS special issue "Nature and nurture in brain
      development and neurological disorders", based on presentations at the annual
      INMED/TINS symposium (http://inmednet.com/).

PMID- 16806506
TI  - D-serine signalling in the brain: friend and foe.
AB  - Neurons and glia talk to each other at synapses. Glia sense the level of synaptic
      activity and consequently regulate its efficacy via the release of
      neuromodulators. One such glia-derived modulator is D-serine, an amino acid that
      serves as an endogenous ligand for the strychnine-insensitive glycine-binding
      site of NMDA glutamate receptors. Here, we provide an overview of recent findings
      on the mechanisms of its synthesis, release and clearance at synapses, with an
      emphasis on the dichotomy of behaviour of this novel messenger in the brain. The
      discovery of the good and ugly faces of this gliotransmitter is an important
      issue of modern neuroscience that has repercussions for the treatment of brain
      disorders.

PMID- 16806507
TI  - alphaCaMKII autophosphorylation: a fast track to memory.
AB  - Alpha Ca(2+)/calmodulin-dependent kinase II (alphaCaMKII), the major synaptic
      protein in the forebrain, can switch into a state of autonomous activity upon
      autophosphorylation. It has been proposed that alphaCaMKII autophosphorylation
      mediates long-term memory (LTM) storage. However, recent evidence shows that
      synaptic stimulation and behavioural training only transiently increase the
      autonomous alphaCaMKII activity, implicating alphaCaMKII autophosphorylation in
      LTM formation rather than storage. Consistent with this, mutant mice deficient in
      alphaCaMKII autophosphorylation can store LTM after a massed training protocol,
      but cannot form LTM after a single trial. Here, we review evidence that the role
      of alphaCaMKII autophosphorylation is in fact to enable LTM formation after a
      single training trial, possibly by regulating LTM consolidation-specific
      transcription.

PMID- 16806508
TI  - Inducible proteopathies.
AB  - Numerous degenerative diseases are characterized by the aberrant polymerization
      and accumulation of specific proteins. These proteopathies include neurological
      disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease
      and the prion diseases, in addition to diverse systemic disorders, particularly
      the amyloidoses. The prion diseases have been shown to be transmissible by an
      alternative conformation of the normal cellular prion protein. Other
      proteopathies have been thought to be non-transmissible, but there is growing
      evidence that some systemic and cerebral amyloidoses can be induced by exposure
      of susceptible hosts to cognate molecular templates. As we review here, the
      mechanistic similarities among these diseases provide unprecedented opportunities
      for elucidating the induction of protein misfolding and assembly in vivo, and for
      developing an integrated therapeutic approach to degenerative proteopathies.

PMID- 16806510
TI  - Synaptic plasticity: one STEP at a time.
AB  - Striatal enriched tyrosine phosphatase (STEP) has recently been identified as a
      crucial player in the regulation of synaptic function. It is restricted to
      neurons within the CNS and acts by downregulating the activity of MAP kinases,
      the tyrosine kinase Fyn and NMDA receptors. By modulating these substrates, STEP
      acts on several parallel pathways that impact upon the progression of synaptic
      plasticity. Here, we review recent advances that demonstrate the importance of
      STEP in normal cognitive function, and its possible involvement in cognitive
      disorders such as Alzheimer's disease.

PMID- 16806511
TI  - Blueprints for behavior: genetic specification of neural circuitry for innate
      behaviors.
AB  - Innate behaviors offer a unique opportunity to use genetic analysis to dissect
      and characterize the neural substrates of complex behavioral programs. Courtship
      in Drosophila involves a complex series of stereotyped behaviors that include
      numerous exchanges of multimodal sensory information over time. As we will
      discuss in this review, recent work has demonstrated that male-specific
      expression of Fruitless transcription factors (Fru(M) proteins) is necessary and
      sufficient to confer the potential for male courtship behaviors. Fru(M) factors
      program neurons of the male central and peripheral nervous systems whose function
      is dedicated to sexual behaviors. This circuitry seems to integrate sensory
      information to define behavioral states and regulate conserved neural elements
      for sex-specific behavioral output. The principles that govern the circuitry
      specified by Fru(M) expression might also operate in subcortical networks that
      govern innate behaviors in mammals.

PMID- 16806512
TI  - Dynamic auditory processing, musical experience and language development.
AB  - Children with language-learning impairments (LLI) form a heterogeneous population
      with the majority having both spoken and written language deficits as well as
      sensorimotor deficits, specifically those related to dynamic processing. Research
      has focused on whether or not sensorimotor deficits, specifically auditory
      spectrotemporal processing deficits, cause phonological deficit, leading to
      language and reading impairments. New trends aimed at resolving this question
      include prospective longitudinal studies of genetically at-risk infants,
      electrophysiological and neuroimaging studies, and studies aimed at evaluating
      the effects of auditory training (including musical training) on brain
      organization for language. Better understanding of the origins of developmental
      LLI will advance our understanding of the neurobiological mechanisms underlying
      individual differences in language development and lead to more effective
      educational and intervention strategies. This review is part of the INMED/TINS
      special issue "Nature and nurture in brain development and neurological
      disorders", based on presentations at the annual INMED/TINS symposium
      (http://inmednet.com/).

PMID- 16806513
TI  - Viral infections in the developing and mature brain.
AB  - A number of different RNA and DNA viruses can invade the brain and cause
      neurological dysfunction. These range from the tiny polio picornavirus, which has
      only 7kb of RNA genetic code that preferentially infects motor neurons, to the
      relatively large cytomegalovirus, which has >100 genes in its 235kb DNA genome
      and causes various neurological problems in the developing brain but is
      comparatively harmless to adults. This brief overview of some aspects of
      neurovirology addresses the complex problems that underlie an appreciation of the
      contribution of viral infections to brain disease. [This review is part of the
      INMED/TINS special issue "Nature and nurture in brain development and
      neurological disorders", based on presentations at the annual INMED/TINS
      symposium (http://inmednet.com/).]

PMID- 16806514
TI  - Therapeutic strategies towards HIV-1 infection in macrophages.
AB  - It is widely recognized that macrophages (M/M) represent a crucial target of HIV
      1 in the body and play a pivotal role in the pathogenic progression of HIV-1
      infection. This strongly supports the clinical relevance of therapeutic
      strategies able to interfere with HIV-1 replication in M/M. In vitro studies
      showed that nucleoside analogue inhibitors of HIV-1 reverse transcriptase have
      potent antiviral activity in M/M, although the limited penetration of these
      compounds in sequestered body compartments and low phosphorylation ability of
      M/M, suggest that a phosphonate group linked to NRTIs may confer greater anti-HIV
      1 activity in M/M. Differently, the antiviral activity of non-nucleoside reverse
      transcriptase inhibitors in M/M is similar to that found in CD4+ lymphocytes.
      Interestingly, protease inhibitors, acting at a post-integrational stage of HIV-1
      life-cycle are the only drugs active in chronically infected M/M. A careful
      analysis of the distribution of antiviral drugs, and the assessment of their
      activity in M/M, represent key factors in the development of therapeutic
      strategies aimed to the treatment of HIV-1-infected patients. Moreover, testing
      new and promising antiviral compounds in such cells may provide crucial hints
      about their efficacy in patients infected by HIV.

PMID- 16806515
TI  - Respiratory syncytial virus infections: recent prospects for control.
AB  - Respiratory syncytial virus (RSV) infections remain a significant public health
      problem throughout the world, although recently developed and clinically approved
      anti-RSV antibodies administered prophylactically to at-risk populations appear
      to have significantly affected the disease development. Much effort has been
      expended to develop effective anti-RSV therapies, using both in vitro assay
      systems and mouse, cotton rat, and primate models, with several products now in
      various stages of clinical study. Several products are also being considered for
      the treatment of clinical symptoms of RSV. In this review, updates on the status
      of the approved anti-RSV antibodies, ribavirin, and recent results of studies
      with potential new anti-RSV compounds are summarized and discussed.

PMID- 16806516
TI  - The distribution of substance P and met-enkephalin in vocal control nuclei among
      oscine species and its relation to song complexity.
AB  - Substance P (SP) and methionine-enkephalin (ENK) have been reported to appear in
      song control nuclei of oscine species. However, it remains unknown whether or not
      SP and ENK location in song control nuclei is correlated with song behavior. To
      address this issue, the present study first measured two variables for song
      complexity, i.e., song repertoire sizes, and syllable repertoire sizes in 11
      oscine species. Then, we examined the distribution of SP and ENK in four control
      nuclei, two in the motor pathway, i.e., HVC and the robust nucleus of arcopallium
      (RA), and the other two in the forebrain pathway, i.e., Area X and the lateral
      magnocellular nucleus of the anterior nidopallium (LMAN). Finally, we measured
      the relative amounts of immunoreactivity for SP and ENK in song control nuclei,
      and tested whether they were correlated with song complexity. Our results showed
      that: (1) SP and ENK were broadly distributed in the song control nuclei of
      studied species. However, SP immunohistochemistry was more robust in comparison
      with ENK, and SP is generally more abundant in the two song learning nuclei than
      those in the two song producing ones; (2) SP and ENK staining patterns in song
      control nuclei did not show any obvious phylogenetic relationship among studied
      oscine species; (3) there was a significant correlation between the relative
      amounts of immunoreactivity for SP and the song and syllable repertoire sizes.
      Our results suggest that SP or ENK might be involved in song behavior, such as
      birdsong learning or memory.

PMID- 16806517
TI  - Behavioral and hippocampal changes after prenatal invasive interventions with
      possible relevance to schizophrenia.
AB  - In an attempt to model neurodevelopmental defects that may contribute to the
      outbreak of schizophrenia after adolescence, the present study examined the
      effects of prenatal interventions in rats, including injections of kainic acid,
      on motor, cognitive and social behaviour, which was assessed repeatedly between
      PDs 56-62 (week 8) and 168-174 (week 24), as well as on hippocampal morphology.
      As compared to untreated controls (n=5-9), the offspring (n=12 or 16) of treated
      mothers exhibited shorter latencies to leave a dark box and enter an illuminated
      field on weeks 12, 16 and 20, a higher number of perseverations in a T-maze
      alternation task on weeks 16 and 20, longer nose contacts with strange and
      familiar partners in a social interaction test on weeks 12 and 16 and lower
      weight gains over the course of testing. They also had shorter pyramidal cells in
      hippocampal area CA3. Thus, the prenatally treated offspring showed certain
      alterations in their brains and behaviour that resembled the human condition of
      schizophrenia (e.g., changes at cell level in the hippocampus, perseverative
      behaviour, lower weight gains), although others (e.g., increased social contacts)
      did not.

PMID- 16806518
TI  - Spatial choices of rats based on abstract visual information: Pattern- or
      configuration-discrimination?
AB  - Animals demonstrate their ability to represent a geometric configuration of their
      environment and to use this information for spatial decisions in their response
      space in many situations. In presented experiment, we examined the ability of
      rats to interpret a configuration of abstract visual stimuli to make spatial
      decisions in a real response space. We tested whether they are able to interpret
      spatial configuration of abstract stimuli or whether they perceive such visual
      stimuli simply as geometric patterns associated to particular spatial choices.
      The rats were tested in a Skinner box with four nosing holes in the transparent
      front wall through which a computer screen was visible. According to the visual
      stimuli on the screen, the rats should choose the appropriate nosing hole to
      obtain a reward. We compared two groups of rats: the first group was exposed to
      the visual stimuli designed as a representation of the response space: the
      position of rewarded nosing hole was shown in relation to other nosing holes. The
      second group was exposed to one of four geometric patterns associated to one of
      the four nosing holes but without any implicit information about the response
      space. The results suggested that rats using the stimuli with information about
      configuration were significantly more successful than rats trained to respond to
      visual stimuli unrelated to the geometry of the environment.

PMID- 16806519
TI  - Antidepressant-like activity of selective serotonin reuptake inhibitors combined
      with a NK1 receptor antagonist in the mouse forced swimming test.
AB  - Substance P antagonists of the neurokinin-1 receptor type (NK1) have growing
      interest as new antidepressant therapies. It has been postulated that these drugs
      exert this putative therapeutic effect without direct interactions with serotonin
      (5-HT) neurons. In line with this assumption, previous intracerebral in vivo
      microdialysis experiments provided evidence that the NK1 receptor antagonists did
      not change basal cortical 5-HT levels. However, we found that increases in
      cortical 5-HT overflow caused by systemic injection of the selective serotonin
      reuptake inhibitor (SSRI), paroxetine was higher in freely moving (C57BL/6x129sv)
      NK1-/- mutants than in wild-type NK1+/+ mice. More recently, a pharmacological
      study has led to a similar conclusion since GR205171, a NK1 receptor antagonist,
      potentiated paroxetine-induced increases in cortical 5-HT dialysate following its
      acute systemic or intra-raphe administration to wild-type mice . In the present
      study, we tested whether an acute combination of SSRI and NK1 receptor antagonist
      could display antidepressant-like activity using the forced swimming test in
      Swiss mice. We found that a single systemic dose of GR205171 (10 and 30 mg/kg,
      i.p.) had no effect by itself. However, it selectively potentiated the
      antidepressant-like activity of subactive doses of two serotonergic
      antidepressant drugs, citalopram and paroxetine (without psychomotor stimulant
      activity), but not that of noradrenaline reuptake inhibitor, desipramine. In
      agreement with neurochemical data, the present study confirms that co
      administration of a NK1 receptor antagonist with an antidepressant drug such as a
      SSRI may have a therapeutic potential to improve the treatment of major
      depressive episodes in human compared to SSRI alone.

PMID- 16806520
TI  - Communal nesting, an early social enrichment, increases the adult anxiety-like
      response and shapes the role of social context in modulating the emotional
      behavior.
AB  - Early experiences affect brain function and behavior at adulthood. Being reared
      in a communal nest (CN), consisting in a single nest where three mothers keep
      their pups together and share care-giving behavior from birth to weaning
      (postnatal day 25), provides a highly stimulating social environment to the
      developing pup. CN characterizes the natural ecological niche of many rodent
      species including the mouse. Here we show that, at adulthood, compared to mice
      reared in standard laboratory conditions (SN), CN reared mice displayed increased
      anxiety-like behavior, performing more thigmotaxis in the open field and spending
      less time in the open arms of the plus-maze. Furthermore, we showed that social
      context (being alone or with a familiar conspecific in the test apparatus)
      affects the emotional response in both the plus-maze and open field test and that
      the relevance of social context changes according to the early social
      experiences. In particular, CN mice display higher levels of anxiety-like
      behavior, compared to SN mice, only when alone but not in the presence of a
      familiar conspecific. Overall, in line with previous findings, the present study
      suggests that CN mice have a more elaborate social and emotional behavior
      compared to SN mice and thus may be more appropriate to investigate socio
      emotional impairments, in particular in the case of mouse models of
      neurodevelopmental disorders, such as autism, or anxiety and mood disorders.

PMID- 16806521
TI  - Decreased prefrontal activation during letter fluency task in adults with
      pervasive developmental disorders: a near-infrared spectroscopy study.
AB  - Functional neuroimaging studies have suggested that dysfunction of prefrontal
      cortex (PFC) is present in persons with pervasive developmental disorders (PDD).
      Recently, the development of near-infrared spectroscopy (NIRS) has enabled
      noninvasive bedside measurement of regional cerebral blood volume. Although NIRS
      enables the noninvasive clarification of brain functions in many psychiatric
      disorders, it has not yet been used to examine subjects with PDD. The aim of our
      study was to conduct an NIRS cognitive activation study to verify PFC dysfunction
      in PDD. The subjects were 10 adults with PDD and 10 age- and gender-matched
      healthy subjects. Hemoglobin concentration changes were measured with a 24
      channel NIRS machine during the letter fluency task. While the number of words
      generated during the letter fluency task did not differ significantly between
      groups, the analysis of covariance including IQ as a confounding covariate showed
      that the PDD group was associated with bilateral reduction in oxy-hemoglobin
      concentration change as compared with the control group. The statistical results
      did not change when only IQ-matched high-functioning subjects (N=7) were
      included. Moreover, reduced oxy-hemoglobin concentration change for the right PFC
      was significantly correlated with verbal communication deficits within the PDD
      group. The present findings are consistent with proposed prefrontal dysfunction
      in PDD subjects identified by other neuroimaging modalities. The present results
      may be also potentially useful for applying NIRS to clinical settings of child
      psychiatry.

PMID- 16806522
TI  - Effects of medial amygdala inactivation on a panic-related behavior.
AB  - In the last years, the role played by the medial nucleus of the amygdala (MeA) in
      the modulation of fear- and anxiety-related behaviors has been increasingly
      investigated. This nucleus plays an important role in the processing of predator
      odor-induced defensive reactions, i.e. freezing and risk-assessment behaviors.
      Immunohistochemical evidence also indicates that the MeA may be involved in the
      regulation of escape, a defensive behavior related to panic attacks. In this
      study, we further addressed this question by investigating the effects of the
      reversible inactivation of the nucleus on escape behavior generated in male
      Wistar rats by two different aversive stimuli, electrical stimulation of the
      dorsal periaqueductal gray matter (dPAG) and exposure to one of the open arms of
      the elevated T-maze. Results showed that intra-MeA administration of either the
      reversible sodium channel blocker lidocaine (34 nmol/0.2 microl) or the GABA(A)
      receptor agonist muscimol (0.22 nmol/0.2 microl) raised the threshold of aversive
      electrical stimulation, increasing the amount of current that applied to the dPAG
      evokes escape, an antiaversive effect. Local microinjection of muscimol (0.22
      nmol/0.2 microl) inhibited escape behavior in the elevated T-maze, also
      suggesting an antiaversive effect. In this latter test, muscimol did not affect
      inhibitory avoidance, a behavior associated with generalized anxiety disorder.
      Muscimol effect in the elevated T-maze was independent of changes in general
      exploratory activity as measured in an open-field. Taken together, our data
      corroborate previous evidences suggesting that the MeA is involved in the
      modulation of escape. Dysfunction of this regulatory mechanism may be of
      relevance in the genesis/maintenance of panic disorder.

PMID- 16806523
TI  - Sulfotransferase activities towards xenobiotics and estradiol in two marine fish
      species (Mullus barbatus and Lepidorhombus boscii): characterization and
      inhibition by endocrine disrupters.
AB  - We have characterized hepatic phenol sulfotransferase (SULT) activities in two
      benthic fish species, Mullus barbatus and Lepidorhombus boscii, using p
      nitrophenol, dopamine, 17beta-estradiol, 4-nonylphenol, and 1-naphthol as
      substrates. High affinity sulfation of 17beta-estradiol was observed in both
      species (Km=28-75 nM), suggesting the presence of a specific estrogen
      sulfotransferase that catalyzes the formation of estradiol-3 sulfate. Among the
      tested compounds, 1-naphthol was the most effective substrate for sulfation, with
      Vmax/Km ratios several hundred-fold higher than the other substrates examined.
      Both species sulfated the tested compounds, but only M. barbatus was able to
      sulfate dopamine. We also tested the inhibitory effects of common marine
      pollutants with estrogenic (4-nonylphenol) and androgenic (tributyltin,
      triphenyltin) properties on p-nitrophenol and 17beta-estradiol SULT activities. 4
      Nonylphenol and triphenyltin inhibited sulfation of both substrates at micromolar
      concentrations in both species. However, tributyltin was only effective against
      SULTs from L. boscii, again at micromolar concentrations. The data indicate that
      M. barbatus and L. boscii are able to sulfate a range of xenobiotics and
      endogenous compounds, and inhibition of these activities by environmental
      pollutants may contribute to the known toxic effects of these compounds.

PMID- 16806524
TI  - Oral toxicity of the microcystin-containing cyanobacterium Planktothrix rubescens
      in European whitefish (Coregonus lavaretus).
AB  - The microcystin-producing cyanobacterium Planktothrix is one of the most
      widespread genera amongst toxin producing cyanobacteria in European lakes. In
      particular, the metalimnic blooms of Planktothrix rubescens have been associated
      with growing problems in the professional freshwater fishery as a decrease in
      yearly yields in the important coregonids fishery often coincides with the
      appearance of P. rubescens. P. rubescens is a cyanobacterial species known to
      produce toxic compounds, e.g. microcystins. Although microcystins have been
      reported to affect fish health, behaviour, development and growth and have also
      been associated with feral fish kills, there is currently no specific information
      on the effects of toxic Planktothrix filaments in fish and especially coregonids.
      Therefore, the aim of this study was to investigate the effects of an
      environmentally relevant dose of P. rubescens filaments orally applied to
      coregonids and to discuss the findings in the context of microcystin toxicity
      previously reported in carp and trout. A single dose of P. rubescens culture, at
      a density of 80,000 cells per 120 microl, was applied to coregonids thus
      corresponding to 0.6-0.9 microg microcystin-LR(equiv.)/kg body weight.
      Behavioural changes and opercular beat rates, growth, hepatosomatic index,
      condition and plasma glucose were determined. Liver, kidney, gill and the
      gastrointestinal tract were assessed histopathologically and
      immunohistologically. Exposed fish showed behavioural changes, increased
      opercular beat rates and elevated plasma glucose levels, possibly representing a
      physiological stress response. Histopathological alterations in liver,
      gastrointestinal tract and kidney, also immunopositive for microcystin suggested
      causality of tissue damage and the in situ presence of microcystins. The observed
      combination of stress and organ damage may explain the frequently reduced weight
      and thus the fitness noted in coregonids subjected to regular occurrences of
      stratified and dispersed P. rubescens blooms, e.g. in lake Ammersee, Bavaria,
      Germany.

PMID- 16806525
TI  - Osmoregulation and tissue water regulation in the freshwater red crab
      Dilocarcinus pagei (Crustacea, Decapoda), and the effect of waterborne inorganic
      lead.
AB  - Inorganic lead has been measured in high concentrations in certain streams in
      Brazil. This study has evaluated the osmoregulatory effects of lead on the native
      freshwater red crab Dilocarcinus pagei. In order to probe its osmoregulatory and
      tissue volume regulatory capabilities and how it would be affected by lead, the
      crab has been submitted to individual and combined salt and chemical stresses
      (Pb2+). Male crabs were exposed for 10 days to either: (1) control (freshwater,
      FW), (2) brackish water of salinity 15 (BW), (3) inorganic lead in freshwater
      (FWPb), and (4) inorganic lead in brackish water (BWPb), 2.7 mgPb/L. In vivo,
      whole crabs lost weight transiently when exposed to Pb2+, both in FW and in BW.
      Haemolymph osmolality and ion concentrations increased and remained elevated upon
      exposure of crabs to BW, with or without Pb2+, showing a trend to hyper
      conformation. In vitro, muscle weight decreased in isosmotic conditions upon
      exposure to Pb2+. Na+, Cl-, and ninhydrin positive substances (NPS) were
      increased in muscle exposed to hyperosmotic saline, well above what would be
      expected from simple efflux of water, suggesting a partial regulatory volume
      increase (RVI) capacity. This partial RVI involves the Na+, K+, 2Cl- 
      cotransporter and the Na+/H+ exchanger on Na+ and Cl- uptake, as judged from
      further decreases in muscle weight in the presence of the respective inhibitors.
      A breakdown of proteins into NPS seems to follow the uptake of inorganic ions.
      Pb2+ has affected water and ion movements in D. pagei both in the whole animal
      and in the isolated tissue. This study has highlighted the relevance of
      evaluating tissue volume regulation in aquatic animals confronted with metal
      polluted waters.

PMID- 16806526
TI  - Haematological responses of acute nitrite exposure in walleye (Sander vitreus).
AB  - Nitrite (NO2-) is a toxic intermediary of the bacterial oxidation of nitrogenous
      wastes (e.g. ammonia) in an aquatic environment. It becomes most lethal when
      oxygen becomes limited due to high fish densities or in the presence of high
      bacterial activity due to waste build-up-both situations commonly found in
      intensive aquaculture. To date however, little is known about how this toxin
      affects the physiology of walleye, an intended culture species, particularly in
      intensive re-circulating systems. This study aims to define threshold
      concentrations of nitrite that affect haemoglobin-oxygen affinity and carrying
      capacity in walleye. During in vivo tests, fish (N=20) were subjected to a medium
      effective concentration (EC50) of nitrite (0.9 mmol L(-1)) for 48 h while the
      effects of nitrite accumulation on blood properties were measured. The effects of
      oxygenation state on red blood cell (RBC) nitrite uptake and metHb formation was
      further investigated by in vitro tonometry. In vitro nitrite exposure to 3 mmol
      L(-1) resulted in a significantly higher methaemoglobin formation in 50% air
      saturated than 100% air saturated RBCs. Both cell water content and haematocrit
      decreased with time in 50% air saturated treatments, whereas total Hb remained
      constant, suggesting a reduction in RBC volume. Similar effects were observed
      during 48 h in vivo and in vitro nitrite exposure tests, indicating the reduction
      in RBC volume likely was not the result of a catecholamine response. Walleye were
      found to be tolerant to an accumulation of blood-NO2- levels similar to common
      carp, a highly Mean Cellular Volume (MCV) tolerant species, before succumbing to
      methaemoglobinemia. The elevated tolerance to nitrite of walleye is a beneficial
      characteristic for successful rearing in a culture setting, where reduced oxygen
      and elevated MCV levels are prevalent. The findings from this study may be used
      in developing guidelines for species-specific management of nitrogenous wastes in
      aquaculture.

PMID- 16806527
TI  - 2-Cys peroxiredoxins from Schistosoma japonicum: the expression profile and
      localization in the life cycle.
AB  - Peroxiredoxin (Prx) is known to be an antioxidant protein that protects the
      organisms against various oxidative stresses and functions as a signal
      transductor. Here, we determined the full-length cDNA sequences of three types of
      Prx from an Asian blood fluke, Schistosoma japonicum: Prx-1, Prx-2 and Prx-3.
      According to the deduced amino acid sequences, only Prx-3 had a mitochondria
      targeting sequence. Using RT-PCR, it was shown that these Prx genes were
      constitutively expressed in the eggs, cercariae and adult worms of the
      schistosome. Western blot analysis using antisera specific for each Prx revealed
      that all the three Prx proteins existed in these developmental stages. By
      immunolocalization analysis, Prx-1 existed on the surface of a miracidium and in
      the space between a miracidium and an eggshell. Furthermore, Prx-1 was deposited
      in the host tissues around the eggs. In adult worms, Prx-1 was not only expressed
      in the tegument, but also contained in their excretory/secretory products. The
      surface of the 7 day-schistosomula was stained with anti-Prx-1 antiserum. On the
      other hand, Prx-2 only existed inside the miracidia in eggs. In addition, Prx-2
      was mainly detected in the sub-tegumental tissues, parenchyma, vitelline gland
      and gut epithelium of the adult worms, but was not detected in the tegument of
      adults and schistosomula. Taken together with previous reports by other
      investigators, these data suggest that Prx-1 acts to protect the parasite against
      the ROS produced by host immune cells, and that Prx-2 plays important roles in
      intracellular redox signaling and/or in the reduction of ROS generated through
      the hemoglobinolytic process in the digestive tract.

PMID- 16806528
TI  - The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase of
      Trypanosomatidae and the glycosomal redox balance of insect stages of Trypanosoma
      brucei and Leishmania spp.
AB  - The genes for the mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase
      were identified in Trypanosoma brucei and Leishmania major genomes. We have
      expressed the L. major gene in Saccharomyces cerevisiae and confirmed the
      subcellular localization and activity of the produced enzyme. Using cultured T.
      brucei procyclic and Leishmania mexicana promastigote cells with a permeabilized
      plasma membrane and containing intact glycosomes, it was shown that
      dihydroxyacetone phosphate is converted into pyruvate, and stimulates oxygen
      consumption, indicating that all components of the glycerol 3
      phosphate/dihydoxyacetone phosphate shuttle between glycosomes and mitochondrion
      are present in these insect stages of both organisms. A computer model has been
      prepared for the energy and carbohydrate metabolism of these cells. It was used
      in an elementary mode analysis to get insight into the metabolic role of the
      shuttle in these insect-stage parasites. Our analysis suggests that the shuttle
      fulfils important roles for these organisms, albeit different from its well-known
      function in the T. brucei bloodstream form. It allows (1) a high yield of further
      metabolizable glycolytic products by decreasing the need to produce a secreted
      end product of glycosomal metabolism, succinate; (2) the consumption of glycerol
      and glycerol 3-phosphate derived from lipids; and (3) to keep the redox balance
      of the glycosome finely tuned due to a highly flexible and redundant system.

PMID- 16806529
TI  - Post-translational signal peptide cleavage controls differential epitope
      recognition in the QP-rich domain of recombinant Theileria parva PIM.
AB  - The presence of the schizont stage of the obligate intracellular parasites
      Theileria parva or T. annulata in the cytoplasm of an infected leukocyte results
      in host cell transformation via a mechanism that has not yet been elucidated.
      Proteins, secreted by the schizont, or expressed on its surface, are of interest
      as they can interact with host cell molecules that regulate host cell
      proliferation and/or survival. The major schizont surface protein is the
      polymorphic immunodominant molecule, PIM, which contains a large glutamine- and
      proline-rich domain (QP-rd) that protrudes into the host cell cytoplasm.
      Analyzing QP-rd generated by in vitro transcription/translation, we found that
      the signal peptide was efficiently cleaved post-translationally upon addition of
      T cell lysate or canine pancreatic microsomes, whereas signal peptide cleavage of
      a control protein only occurred cotranslationally and in the presence of
      microsomal membranes. The QP-rd of PIM migrated anomalously in SDS-PAGE and
      removal of the 19 amino acids corresponding to the predicted signal peptide
      caused a decrease in apparent molecular mass of 24kDa. The molecule was analyzed
      using monoclonal antibodies that recognize a set of previously defined PIM
      epitopes. Depending on the presence or the absence of the signal peptide, two
      conformational states could be demonstrated that are differentially recognized,
      with N-terminal epitopes becoming readily accessible upon signal peptide removal,
      and C-terminal epitopes becoming masked. Similar observations were made when the
      QP-rd of PIM was expressed in bacteria. Our observations could also be of
      relevance to other schizont proteins. A recent analysis of the proteomes of T.
      parva and T. annulata revealed the presence of a large family of potentially
      secreted proteins, characterized by the presence of large stretches of amino
      acids that are also particularly rich in QP-residues.

PMID- 16806530
TI  - Overfeeding during lactation modulates insulin and leptin signaling cascade in
      rats' hearts.
AB  - Insulin has been described as a potential mediator of intrinsic responses to the
      nutritional state in the heart due to its effects on cardiac metabolism, mainly
      on glucose transport. It has been demonstrated that leptin can act through some
      components of the insulin-signaling cascade. We investigated the association
      between overfeeding during lactation and alterations of insulin and leptin
      signaling in the heart. In summary, we analyzed a feasible cross-talk between
      insulin and leptin through the study of some key proteins of their cascades in
      the heart. In order to study the effect of overfeeding on these cascades, Wistar
      rats were overfed through litter size reduction to only three pups. At 10 and 21
      days of life, key proteins such as insulin receptor, leptin receptor, PI3-kinase,
      JAK2, STAT3, and GLUT4 were measured by Western blotting. Furthermore, the pups'
      weight and the plasma levels of insulin, leptin and glucose were determined.
      Overfed animals were overweight, had high insulin and leptin plasma levels, and
      displayed an activation of insulin and leptin cascade, leading to an increased
      translocation of GLUT4. We suggest that overfeeding during lactation probably
      alters cardiac metabolism, through the activation of a modulated cross-talk
      between leptin and insulin cascades.

PMID- 16806531
TI  - The role of Sp1 and Sp3 in the constitutive DPYD gene expression.
AB  - Dihydropyrimidine dehydrogenase (DPD), the initial and rate-limiting enzyme in
      the 5-fluorouracil (5-FU) catabolic pathway, has been implicated as one of the
      factors determining the efficacy and toxicity of the anticancer agent 5-FU.
      Studies have attributed variation in DPD activity partially to alterations at the
      transcriptional level of DPYD gene. We investigated the transcription factors
      implicated in the constitutive expression of DPYD by utilizing a 174-bp fragment
      of the DPYD promoter region in which three consensus Sp protein binding sites
      (SpA, SpB and SpC) were predicted. The binding of Sp1 and Sp3 transcription
      factors to this region was detected by electrophoretic mobility shift and
      chromatin immunoprecipitation assays. By ectopically expressing human Sp1 and Sp3
      in Sp-deficient Drosophila S2 cells, we demonstrated that Sp1 is a strong
      activator, while Sp3 by its own is a weak activator of the DPYD promoter.
      Moreover, Sp3 may serve as a competitor of Sp1, thus decreasing the Sp1 induced
      promoter activity. SpA, SpB and SpC sites are all Sp1 inducible. In the full
      activation of the DPYD promoter in human cell lines, the SpB site is essential;
      the SpC site works cooperatively with SpB, while SpA has minor promoter activity.
      These studies provide further insight into the molecular mechanisms underlying
      the heterogeneity of DPD activity, and may facilitate the efficacy and safety of
      5-FU-based chemotherapy.

PMID- 16806532
TI  - Identification and expression of a new splicing variant of FAD-sulfhydryl oxidase
      in adult rat brain.
AB  - Flavoproteins of the quiescin/sulfhydryl oxidase (QSOX) family catalyze oxidation
      of peptide and protein thiols to disulfides with the reduction of oxygen to
      hydrogen peroxide. We report here the molecular cloning of a new putative
      sulfhydryl oxidase cDNA, rQSOX-L (GenBank Accession no ), from adult rat brain
      and its expression studied by RT-PCR, Northern and Western blots in rat tissues.
      DNA-sequencing demonstrated the existence of two cDNAs in rat cortex,
      corresponding to a long transcript (rQSOX-L) and a short transcript (rQSOX-S)
      which differed by 851 nucleotides due to alternative splicing. The new
      transcript, rQSOX-L (3356 nucleotides), was specifically expressed in brain,
      hypophysis, heart, testis and seminal vesicle. The distribution of this variant
      is not homogeneous in the different tissues studied and suggests a complex gene
      regulation. The full-length rQSOX-L cDNA has an open reading frame of 2250-bp
      encoding a protein of 750 amino acids that contains a signal peptide sequence, a
      protein-disulfide-isomerase-type thioredoxin and ERV1-ALR domains and a long form
      specific C-terminal extension. The rQSOX-L protein is highly homologous to
      members of the sulfhydryl oxidase/Quiescin family and contains particularly two
      potential sites for N-glycosylation. This protein isoform was specifically
      detected in rat brain tissues in opposition to the low molecular form that was
      ubiquitous. Matrix-assisted laser desorption/ionization time of flight mass
      spectrometry analysis of the immunoprecipitate tryptic fragments allowed the
      identification of rQSOX-L protein.

PMID- 16806533
TI  - Intracellular localization of RORalpha is isoform and cell line-dependent.
AB  - The retinoid-related orphan receptor alpha (RORalpha) belongs to the nuclear
      receptor superfamily and comprises four isoforms generated by different promotor
      usage and alternative splicing. To better understand its function, the
      subcellular distribution of RORalpha was investigated. We could show that
      subcellular distribution of RORalpha is cell line and isoform-dependent. Isoform
      specific differences were mediated by the A/B domains which with the exception of
      RORalpha1 contain a signal that mediates cytoplasmic localization. The lack of
      this signal in RORalpha1 results in a complete nuclear localization and prevents
      cell membrane association observed for RORalpha2, 3, and 4. The region
      responsible for membrane association was identified as the C-terminal alpha-helix
      12. Furthermore, the hinge region/ligand binding domain mediates nuclear
      localization. Our results show that isoform specific activity of RORalpha is not
      only regulated by different expression and DNA binding affinities but also by
      different subcellular distribution. Different access to the nucleus reveals an
      important mechanism regulating the activity of this constitutively active nuclear
      receptor.

PMID- 16806534
TI  - Iron uptake in fungi: a system for every source.
AB  - Fungi have a remarkable capacity to take up iron when present in any of a wide
      variety of forms, which include free iron ions, low-affinity iron chelates,
      siderophore-iron chelates, transferrin, heme, and hemoglobin. Appropriately,
      these unicellular eukaryotes express a variety of iron uptake systems, some of
      which are unique to fungi and some of which are present in plants and animals, as
      well. The reductive system of uptake relies upon the external reduction of ferric
      salts, chelates, and proteins prior to uptake by a high-affinity, ferrous
      specific, oxidase/permease complex. This system recognizes a broad range of
      substrates. The non-reductive system exhibits specificity for siderophore-iron
      chelates, and transporters of this system exhibit multiple substrate-dependent
      intracellular trafficking events.

PMID- 16806535
TI  - Nocturnal oxygen therapy prevents progress of congestive heart failure with
      central sleep apnea.
AB  - BACKGROUND: Sleep disordered breathing has been reported to be associated with
      congestive heart failure (CHF). Nocturnal oxygen has been shown to abolish apnea.
      The aim of this study is to examine whether nocturnal oxygen reduces sympathetic
      nerve activity, and prevents progress of CHF. METHODS: 93 patients with left
      ventricular ejection fractions < 60%, were examined with overnight saturation
      monitoring for an oxygen desaturation index. Subjects with oxygen desaturation of
      4% > or = 4/h were examined with polysomnography. Apnea-hypopnea index (AHI) was
      calculated as the total number of episodes of apnea and hypopnea per hour of
      sleep. We started nocturnal oxygen for the patients with AHI > or = 20. Urinary
      and plasma catecholamines concentrations, serum brain natriuretic peptide, human
      atrial natriuretic peptide, and endothelial nitric oxide synthase levels were
      measured before and after starting oxygen. RESULTS: Compared among the three
      groups, CHF with central sleep apnea (CHF-CSA) group had significantly higher 24
      h urinary adrenaline (CHF-CSA: 4.411+/-2.940 micromol/day, CHF with obstructive
      sleep apnea (CHF-OSA): 2.686+/-1.084 micromol/day, CHF without apnea (CHF-N):
      3.178+/-1.778 micromol/day, P<0.05). Oxygen therapy significantly decreased AHI
      and 4 serum BNP levels (from 91.75+/-80.35 pg/ml to 52.75+/-45.70 pg/ml, mean
      change=33.85 pg/ml, P=0.0208). Serum eNOS levels were lower in CHF-CSA group and
      CHF-OSA group than in CHF-N group (CHF-CSA: 15.89+/-10.75 pg/ml, CHF-OSA: 7.46+/
      3.91 pg/ml, CHF-N: 27.33+/-14.83 pg/ml, P<0.05). CONCLUSIONS: Nocturnal oxygen
      may prevent progress of CHF with central sleep apnea.

PMID- 16806536
TI  - Using an individualised quality of life measure in older heart failure patients.
AB  - BACKGROUND: Existing tools purporting to measure quality of life in heart failure
      do not allow expression of individual needs and preferences. The Patient
      Generated Index is a recently introduced tool that allows individualised
      assessment of quality of life. METHODS: 59 patients aged 65 years and over with a
      clinical diagnosis of chronic heart failure were administered the Patient
      Generated Index at baseline, 1 week and 12 weeks, along with the Guyatt chronic
      heart failure questionnaire, Minnesota Living with Heart failure questionnaire
      and Short Form-12 tool. Changes in questionnaire scores were used to calculate
      reproducibility and responsiveness to change. Comparison of Patient Generated
      Index scores with the other questionnaires and with New York Heart Association
      class was used to determine construct validity. RESULTS: All four questionnaires
      were completed by >90% of participants. Intraclass correlation coefficients
      denoting reproducibility were high for the Guyatt (0.93) and Minnesota
      questionnaires (0.89), moderate for the Patient Generated Index (0.65) and Short
      Form-12 (0.59). Responsiveness to change was similar for all questionnaires, but
      lower than in previous studies. The Patient Generated Index correlated with New
      York Heart association class and correlated moderately with the other
      questionnaires. The most important domains nominated on the Patient Generated
      Index were walking, performing daily activities, feeling tired and climbing
      stairs. CONCLUSIONS: The Patient Generated Index can be administered successfully
      to older heart failure patients; usefulness is limited by suboptimal
      reproducibility and responsiveness. Impairment of physical function is the factor
      most cited by older heart failure patients affecting their quality of life.

PMID- 16806537
TI  - Doppler echocardiography and tissue Doppler imaging in the healthy rabbit:
      differences of cardiac function during awake and anaesthetised examination.
AB  - OBJECTIVE: In the past years, Doppler echocardiography has evolved into a
      commonly used technique. More recent sophisticated advances in imaging quality
      have substantially improved spatial and temporal resolution allowing the
      adaptation of this technique to small animal models, particularly in rabbits but
      even in mice. Recently, parameters obtained by Tissue Doppler Imaging (TDI) have
      been shown to be more independent of pre- and afterload than classic hemodynamic
      Doppler measurements. Exploration of animal models may require anaesthesia but
      there is only very little information on the effect of anaesthesia on
      echocardiographic parameters in rabbits. METHODS: We therefore performed Doppler
      echocardiographic examinations of 20 wild-type New Zealand White rabbits in awake
      state and under light ketamine-xylazine anaesthesia. Special focus was put on the
      evaluation of global and regional left ventricular systolic and diastolic
      function using TDI and the myocardial performance index (Tei-index). RESULTS:
      Doppler-echocardiographic measurements including TDI in rabbits were feasible to
      assess cardiac morphology and function within a short examination time. There
      were some distinct changes of functional parameters during anaesthesia. Exemplary
      for systolic function, fractional shortening, cardiac output and systolic TDI
      velocity of the lateral wall decreased distinctly. Global left ventricular
      function measured by the Tei-index deteriorated. CONCLUSIONS: Doppler
      echocardiography and TDI can be performed easily, quickly and safely in the
      rabbit. Anaesthesia with the cardiodepressive ketamine-xylazine shows some
      distinct Doppler-echocardiographically measurable negative effects on cardiac
      function. Thus, echocardiography with less cardiodepressive anaesthetic regimes
      or even without anaesthesia after training of the animals should be considered as
      alternatives whenever possible.

PMID- 16806538
TI  - QT dispersion in non-apneic simple snoring patients and the effect of surgical
      therapy on QT dispersion.
AB  - AIM: Increased QT dispersion in cases of obstructive sleep apnea, which may
      induce serious arrhythmias, is a well-known process. However, there is little
      information about the QT dispersion in patients with simple snoring without
      apnea. We investigated QT dispersion in snoring and the effect of surgical
      therapy on QT dispersion. METHODS: One hundred and sixty two patients with simple
      snoring without apnea were included in this study. Patients had polysomnography
      and surface electrocardiography (ECG) on the pre-operative 1st week and post
      operative 4th week. The patients underwent one of the three surgical procedures,
      which include uvulopalatopharyngoplasty, laser assisted uvulopalatoplasty, and
      cautery assisted uvulopalatoplasty. QT dispersion was calculated in each patient
      from pre-operative and post-operative surface ECG. Pre-operative and post
      operative values were compared using the student's t test. P<0.05 was considered
      statistically significant. RESULTS: One hundred and fourteen of the patients were
      male, 48 were female, and the mean age was 35.2+/-14.1 years (range: 21-51). No
      improvements were observed in 9 of the patients. Surgical interventions were
      successful in 153 patients (94%). Post-operative QTc max and QTc dispersion
      values were significantly shortened, and QTc min was increased compared to the
      pre-operative values (449.6+/-6.2 vs. 440.9+/-20.8, and 68.2+/-8.4 vs. 43.8+/
      6.2, and 381.3+/-7.8 vs. 397.0+/-5.9 respectively; P=0.001). CONCLUSION: This
      study shows that QT dispersion is increased in simple snoring patients without
      apnea and that QT dispersion decreases after surgical interventions.

PMID- 16806539
TI  - Ventricular tachycardia associated with hereditary magnesium-losing nephropathy.
AB  - Ventricular tachycardia (VT) can be a life threatening condition which can be
      caused by an underlying electrolyte disturbance, such as hypomagnesaemia. Causes
      of electrolyte disturbances, such as magnesium losing nephropathy, should be
      identified early to allow correct management of the underlying cause of the
      cardiac arrhythmia.

PMID- 16806540
TI  - A novel haplotype in ABCA1 gene effects plasma HDL-C concentration.
AB  - BACKGROUND AND OBJECTIVES: ATP-binding cassette transporter 1 (ABCA1) is a trans
      membrane protein responsible for the efflux of cholesterol and phospholipids
      across the cell membrane, an essential step in the reverse cholesterol transport
      system. This study investigates the effect of five non-synonymous SNPs of ABCA1
      gene on plasma HDL-C levels in Pakistani individuals free of ischemic heart
      disease and stroke. METHODS: Five non-synonymous SNPs were selected after
      sequencing ABCA1 gene in patients of Hypoalphalipoproteinemia. The presence of
      these SNPs was then checked in 200 individuals by using PCR-RFLP. Plasma glucose
      and lipid fractions were measured in fasting state. Ethical approval was obtained
      from the Ethical Review Committee, Aga Khan University and informed consent was
      obtained from all subjects. RESULTS: LL genotype of V825L polymorphism was
      associated with decreased levels of HDL-C [-0.17 (-0.32 to -0.19); P=0.02] and
      P774 allele showed a significant increase in HDL-C levels as compared to T774
      allele [-0.15 (-0.18 to -0.02); P=0.01]. R219K, A399V and V771M polymorphisms did
      not show any association with levels of HDL-C, LDL-C, cholesterol and
      triglycerides. Haplotype analysis between R219K and V825L polymorphisms showed a
      unique interaction between R219 allele and L825 allele. The RL haplotype was
      found to be associated with decreased levels of HDL-C [-0.12 (-0.22 to -0.03);
      P=0.001]. CONCLUSIONS: ABCA1 polymorphisms are associated with varying levels of
      HDL-C in Pakistani individuals. These results warrant further investigations as
      ABCA1 polymorphisms may have a major role in the high incidence of cardiovascular
      disorders in South Asians.

PMID- 16806541
TI  - Bayesian estimation of sensitivity and specificity of serum ELISA and faecal
      culture for diagnosis of paratuberculosis in Greek dairy sheep and goats.
AB  - Latent class models were used to estimate the sensitivity (Se) and the
      specificity (Sp) of a serum ELISA and a faecal culture (FC) method for the
      diagnosis of paratuberculosis separately, in sheep and goats. The estimates were
      obtained by a Bayesian method. Possible dependence of diagnostic errors was
      investigated by comparing models where independence was assumed to models
      allowing for conditional dependence given the true disease status. ROC analysis
      for the serum ELISA was also performed and optimized cut-off values based on the
      misclassification cost term were determined. No evidence of conditional
      dependence was found. Assuming independence, posterior medians and 95% credible
      intervals for the Se(ELISA), Sp(ELISA), Se(FC) and Sp(FC), were 63% (42, 93%),
      95% (90, 98%), 8% (2, 17%) and 98% (95, 100%) in goats and 37% (10, 80%), 97%
      (93, 99%), 16% (2, 48%) and 97% (95, 99%) in sheep. AUC was calculated 0.702 for
      sheep and 0.847 for goats. For the serum ELISA, there is need of species- and
      purpose-specific cut-off selection. For instance, with 20% prevalence situation
      and assuming equal and five-fold cost of a false negative to a false positive
      test result, the optimal cut-off is 0.3 and 0.05 in sheep, respectively, while it
      is 0.6 and 0.1 in goats, respectively. Serum ELISA performed better in goats than
      in sheep. Lowering the cut-off, in relation to the one recommended by the
      manufacturer, improved Se(ELISA) without seriously compromising Sp(ELISA), in
      either species.

PMID- 16806542
TI  - Prediction of human cases of West Nile virus by equine cases, Saskatchewan,
      Canada, 2003.
AB  - In 2003, an outbreak of West Nile virus (WNV) occurred in Saskatchewan, Canada
      from July to September. One-hundred thirty-three horse cases and 947 human cases
      were recorded and data were analyzed retrospectively for evidence of clustering
      to determine if clinical infection in the horse population could be used to
      estimate human risk of infection with WNV. Kulldorff's scan statistic was used to
      identify spatial-temporal clusters in both the human and horse cases. In most
      areas, human clusters were not preceded by horse clusters. In one area, a
      significant cluster of horse cases preceded human cases by 1 week; however, 1
      week does not provide sufficient time for human-health authorities to act and
      provide advance warning for the public.

PMID- 16806543
TI  - Is health insurance affordable for the uninsured?
AB  - In this paper, we investigate the meaning of "affordability" in the context of
      health insurance. Assessing the relationship between the affordability of
      coverage and the large number of uninsured in the U.S. is important for
      understanding the barriers to purchasing coverage and evaluating the role of
      policy in reducing the number of uninsured. We propose several definitions of
      affordability and examine the implications of alternative definitions for
      estimates of the proportion of uninsured who are unable to afford coverage. We
      find that, depending on the definition, health insurance was affordable to
      between one-quarter and three-quarters of the uninsured in the United States in
      2000.

PMID- 16806544
TI  - Quantification of Pyrenophora teres in infected barley leaves using real-time
      PCR.
AB  - Net blotch is a barley foliar disease caused by two forms of Pyrenophora teres:
      Pyrenophora teres f. teres (PTT) and Pyrenophora teres f. maculata (PTM). To
      monitor and quantify their occurrence during the growing season, diagnostic
      system based on real-time PCR was developed. TaqMan MGB (Minor Groove Binder)
      primers and probes were designed that showed high specificity for each of the two
      forms of P. teres. As a host plant internal standard, TaqMan MGB primers and
      probe based on RacB gene sequence were designed. The method was optimised on pure
      fungal DNA and on plasmid standard dilutions. Quantification was accomplished by
      comparing Ct values of unknown samples with those obtained from plasmid standard
      dilutions. The assay detects down to five gene copies per reaction. It is able to
      produce reliable quantitative data over a range of six orders of magnitude. The
      developed assay was used to differentiate and quantify both forms of P. teres in
      infected barley leaves. Correlation R(2)=0.52 was obtained between the Ct values
      and size of symptoms areas in early stage of infection. Application of the TaqMan
      MGB technology to leaf samples collected in 20 barley varieties in the region
      Kromeriz during the growing season of 2003 and 2004 revealed that P. teres f.
      teres predominated in these 2 years. The developed method is an important tool to
      quantify and monitor the dynamics of the two forms of P. teres during the growing
      season.

PMID- 16806545
TI  - High-resolution analysis of catechol-type siderophores using polyamide thin layer
      chromatography.
AB  - The iron-deficient culture supernatant of a soil bacterial strain identified as
      Erwinia sp. was analyzed using a new high-resolution polyamide thin layer
      chromatography (TLC) and a silica TLC. The results showed both TLC methods were
      very effective for separating simple catechol compounds such as 2,3
      dihydroxybenzoic acid (2,3-DHBA) and catechol. However, in the analysis of more
      complicated catechol compounds or true catechol-type siderophores (conjugates of
      2,3-DHBA and amino acids), the polyamide TLC had the higher resolution. Polyamide
      TLC analysis showed that strain S1 produced three distinct catechol-type
      siderophores.

PMID- 16806546
TI  - Individual variability in brain activations associated with episodic retrieval: a
      role for large-scale databases.
AB  - The localization of brain functions using neuroimaging techniques is commonly
      dependent on statistical analyses of groups of subjects in order to identify
      sites of activation, particularly in studies of episodic memory. Exclusive
      reliance on group analysis may be to the detriment of understanding the true
      underlying cognitive nature of brain activations. In this overview, we found that
      the patterns of brain activity associated with episodic retrieval are very
      distinct for individual subjects from the patterns of brain activity at the group
      level. These differences appear to go beyond the relatively small variations due
      to cyctoarchitectonic differences or spatial normalization. We review evidence
      that individual patterns of brain activity vary widely across subjects and are
      reliable over time despite extensive variability. We suggest that varied but
      reliable individual patterns of significant brain activity may be indicative of
      different cognitive strategies used to produce a recognition response. We argue
      that individual analyses in conjunction with group analyses are likely to be
      critical in fully understanding the relationship between retrieval processes and
      underlying neural systems.

PMID- 16806547
TI  - Selective attention to spatial and non-spatial visual stimuli is affected
      differentially by age: effects on event-related brain potentials and performance
      data.
AB  - To assess selective attention processes in young and old adults, behavioral and
      event-related potential (ERP) measures were recorded. Streams of visual stimuli
      were presented from left or right locations (Experiment 1) or from a central
      location and comprising two different spatial frequencies (Experiment 2). In both
      experiments, results were compared in visual-only and visual+auditory stimulus
      context conditions. Participants were forced to respond fast in both experiments,
      while maintaining high accuracy. In Experiment 1, no behavioral effects of aging
      were found; however, an enlargement of the N1 component in the older age group
      suggested that older adults initial selection process was larger than that of
      young adults. A late frontal effect following the P300 elicited by attended non
      targets was larger in the visual+auditory condition than in the visual-only
      condition in the old age group. This effect was interpreted as reflecting a
      memory update of the relevant target location. In Experiment 2, older adults made
      relatively more errors in the visual+auditory condition than in visual-only
      condition, more so than the young adults. Older adults' ERP data were also
      characterized by an enlargement of the occipital selection negativity, compared
      to the young age group. In contrast to experiment 1, no late frontal post-P3
      effect could be found, suggesting that the memory trace of the relevant stimulus
      feature was updated less frequently, explaining the reduction in response
      accuracy in the visual+auditory stimulus context conditions.

PMID- 16806548
TI  - The neuroimaging research process from the participants' perspective.
AB  - The aim of this study was to investigate participants' experiences of taking part
      in research conducted using fMRI or MEG procedures. Forty-four participants
      completed a questionnaire after taking part in either fMRI or MEG experiments;
      the questionnaire asked about experiences of and attitudes toward fMRI/MEG. Ten
      follow-up interviews were conducted to enable an in-depth analysis of these
      attitudes and experiences. The findings were generally positive: all participants
      thought fMRI and MEG were safe procedures, 93% would recommend participating in
      neuroimaging research to their friends and family, and participants were positive
      about participating in future neuroimaging research. However, some negative
      issues were identified. Some participants reported feeling nervous prior to
      scanning procedures, several participants reported side-effects after taking
      part, a number of participants were upset at being in a confined space and some
      participants did not feel confident about exiting the scanner in an emergency.
      Several recommendations for researchers are made, including a virtual tour of the
      scanning equipment during the consenting process in order to better prepare
      potential participants for the scanning experience and to minimize the potential
      psychological discomfort sometimes experienced in neuroimaging research.

PMID- 16806549
TI  - S-Allylcysteine prevents the rat from 3-nitropropionic acid-induced
      hyperactivity, early markers of oxidative stress and mitochondrial dysfunction.
AB  - We investigated the effects of S-allylcysteine (SAC) on early behavioral
      alterations, striatal changes in superoxide dismutase (SOD) activity, lipid
      peroxidation (LP) and mitochondrial dysfunction induced by the systemic infusion
      of 3-nitropropionic acid (3-NPA) to rats. SAC (300 mg/kg, i.p.), given to animals
      30 min before 3-NPA (30 mg/kg, i.p.), prevented the hyperkinetic pattern evoked
      by the toxin. In addition, 3-NPA alone produced decreased activities of manganese
      (Mn-SOD) and copper/zinc-dependent superoxide dismutase (Cu,Zn-SOD), increased
      LP (evaluated as the formation of lipid fluorescent products) and produced
      mitochondrial dysfunction in the striatum (measured as decreased 3-(3,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction). In contrast,
      pretreatment of 3-NPA-injected rats with SAC resulted in a significant prevention
      of all these markers. Our findings suggest that the protective actions of SAC are
      related with its antioxidant properties, which in turn may be accounting for the
      preservation of SOD activity and primary mitochondrial tasks.

PMID- 16806550
TI  - The detection and prevalence of Clostridium botulinum in pig intestinal samples.
AB  - To determine the prevalence of Clostridium botulinum types A, B, E, and/or F in
      pig intestinal samples, different PCR-based methods were compared using
      artificially contaminated faeces. The methods included a multiplex PCR targeted
      to botulinum neurotoxin genes A, B, E, and F or a nested PCR targeted to toxin
      genes B, E, and F, combined with different pre-enrichment protocols and forms of
      templates. A method including the two-step enrichment followed by DNA extraction
      and multiplex PCR yielded the highest number of positives. This assay protocol
      was employed to investigate 100 pig intestinal samples. The sample materials
      studied included colon wall, intestinal content, and mucus peeled from the colon
      wall. Three pigs (3%) were positive for C. botulinum type B, and no other
      toxinotypes were detected in any sample. The number of positive samples was
      higher when colon wall or peeled mucus was analyzed compared to the intestinal
      content. C. botulinum was isolated from two PCR-positive samples and confirmed to
      be type B by PCR. Both isolates were shown to be proteolytic and thus to
      represent C. botulinum group I.

PMID- 16806551
TI  - Fluorescence microscopy of NaCl-stressed, elongated Salmonella and Listeria cells
      reveals the presence of septa in filaments.
AB  - The cell morphology of Salmonella enteritidis and Listeria monocytogenes after
      the application of stress was examined. Cells were stressed by plating the
      bacteria on Tryptone Soya Agar (TSA) plates, with 5-10% NaCl. The plates were
      subsequently incubated for 6 days at 25 degrees C. Finally, the cells were
      harvested and subjected to different fluorescent probes in order to visualize the
      possible presence of septa in elongated cells. Use of the stain 4',6-Diamidino-2
      phenylindole (DAPI), which is a blue fluorescent nucleic acid stain that
      preferentially stains double-stranded DNA, showed clearly the presence of dark
      spots, probably cellular partitions where no nucleic acids were present, in both
      Salmonella and Listeria cells. Another stain, FM 4-64, a lipophilic styryl dye
      for red staining of the inner membrane, showed the presence of highly fluorescent
      spots in Listeria cells, probably indicating the presence of membranes. For
      Salmonella, however, FM 4-64 was not successful in revealing septa in filaments.
      Double staining applied to elongated Listeria cells showed areas with high
      fluorescence in DAPI-staining (DNA-rich spots) which contained low fluorescence
      in FM 4-64-staining (membrane spots) and vice versa, which is a confirmation that
      the elongated cells are indeed composed of several normal size cells.

PMID- 16806552
TI  - Validation of predictive growth models describing superatmospheric oxygen effects
      on Pseudomonas fluorescens and Listeria innocua on fresh-cut lettuce.
AB  - Two microbial growth models predicting the growth of Pseudomonas fluorescens and
      Listeria innocua at superatmospheric oxygen and carbon dioxide concentrations at
      7 degrees C were validated on fresh-cut butterhead lettuce. Cut lettuce was
      inoculated with the same strain of L. innocua as the in vitro experiments. The P.
      fluorescens strain was tagged with a gene encoding green fluorescent protein
      (GFP) in order to distinguish the inoculated strain from contaminating
      Pseudomonaceae. Also growth of aerobic mesophilic and lactic acid bacteria was
      monitored during the experiments. The suggested P. fluorescens model was
      appropriate to predict growth on cut lettuce. L. innocua on the other hand, grew
      considerably slower under in vivo circumstances than predicted. CO(2) had a
      growth promoting effect on L. innocua growing on cut lettuce, whereas in vitro an
      inhibiting effect was observed. Validation parameters are calculated and
      hypotheses to explain the discrepancy between predicted and observed growth of L.
      innocua are provided.

PMID- 16806553
TI  - Microbial diversity and succession during the manufacture and ripening of
      traditional, Spanish, blue-veined Cabrales cheese, as determined by PCR-DGGE.
AB  - The diversity and dynamics of the dominant microbial communities arising during
      the manufacture and ripening of four batches of naturally fermented Cabrales
      cheese were investigated by the PCR-DGGE culture-independent technique. Total
      microbial DNA was extracted from cheese milk, curd and cheese samples and used as
      template material in PCR experiments to amplify the V3 region of the bacterial
      16S rRNA gene, plus the D1 region of the eukaryotic 26S rRNA gene. These regions
      were then analysed using DGGE. Eukaryotic and bacterial bands were identified by
      isolation, reamplification and sequencing. The results were compared to those
      obtained in a previous microbial characterization of the same four batches using
      classical culturing methods. Great variability was recorded between batches by
      the PCR-DGGE technique. This was also shown by culturing, and underlines the
      uniqueness of artisanal products. Lactocococcus lactis subsp. lactis was dominant
      from the cheese milk stage until the end of ripening, whereas populations of
      certain Lactobacillus species appeared during ripening. Populations of species
      never isolated by culturing were found to be numerous by the PCR-DGGE method, in
      particular Lactococcus garvieae and Lactococcus raffinolactis. Other, completely
      unknown lactococci were also detected. The dominant eukaryotic populations from
      day 15 onwards were those of Penicillium roqueforti and Geotrichum candidum.

PMID- 16806554
TI  - Analysis of Campylobacter spp. contamination in broilers from the farm to the
      final meat cuts by using restriction fragment length polymorphism of the
      polymerase chain reaction products.
AB  - We investigated the genotype diversity and dynamics of Campylobacter jejuni and
      Campylobacter coli in six commercial broiler farms during rearing and abattoir
      processing. In total, 223 C. jejuni and 36 C. coli strains isolated (on farm,
      transportation crates, carcasses after defeathering, and chicken wing meat at the
      end of the processing line) were subtyped by PCR-RFLP based on flagellin (fla
      typing) gene. Eleven (C. jejuni) and four (C. coli) different RFLP patterns were
      found. Multiple C. jejuni genotypes were identified in five out of six farms
      (except Farm 5). Furthermore, a clear tendency for dominance of particular
      genotypes was observed in almost all farms except Farm 3. Although diverse C.
      jejuni genotypes were isolated on the farms and transport crates, they were not
      detected in chicken wing cuts at the end of the processing line. We also observed
      varied distribution of types in different sampling stages both at the farm level
      and the processing environment. However, the interpretation of such fluctuations
      is precarious as new types occurred on some occasions, particularly during
      processing. Our results show that chicken wing meat contamination resulted mainly
      from farm strain carryover, and that the carcasses were probably contaminated
      during processing. In addition, the new strain types observed were isolated more
      frequently after defeathering as compared to other processing steps. Therefore,
      this stage, in addition to evisceration, is one of the critical control points in
      the processing line to prevent cross-contamination and for controlling the spread
      of campylobacters.

PMID- 16806555
TI  - Adaptation of a freshwater anammox population to high salinity wastewater.
AB  - For the successful application of anaerobic ammonium oxidation (anammox) in
      wastewater practice it is important to know how to seed new anammox reactors with
      biomass from existing reactors. In this study, a new high salinity anammox
      reactor was inoculated with biomass from a freshwater system. The changes in
      activity and population shifts were monitored. It was shown that freshwater
      anammox bacteria could adapt to salt concentrations as high as 30 gl(-1) provided
      the salt concentration was gradually increased. Higher salt concentrations
      reversibly inhibited anammox bacteria. The nitrogen removal efficiency and
      maximum anammox activity of the salt adapted sludge was very similar to the
      reference freshwater sludge. Fluorescence in situ hybridization analysis revealed
      that the freshwater anammox species Candidatus "Kuenenia stuttgartiensis" was the
      dominant in both salt adapted sludge and freshwater sludge. These results show
      that gradual adaptation may be the key to successful seeding of anammox
      bioreactors.

PMID- 16806556
TI  - Mutations of the Hepatitis C virus protein NS4B on either side of the ER membrane
      affect the efficiency of subgenomic replicons.
AB  - The non-structural protein NS4B of the Hepatitis C virus (HCV) is an integral
      membrane protein located in the endoplasmic reticulum (ER). Although the function
      of the NS4B in the viral life cycle is unknown a critical role in replication has
      been indicated. In order to investigate which components are involved we
      initially introduced restriction sites near the extremities of the NS4B in a
      subgenomic replicon that resulted in the alterations of six amino acid residues.
      This totally abolished replication. We subsequently introduced 14 single point
      mutations into different regions of NS4B based on the current topology model. One
      mutation abolished replication, while most conferred reduced replicon
      establishment and one mutation resulted in improved efficiency. Neither the
      protein processing nor the membrane altering capacity of NS4B was affected.
      Surprisingly, mutations situated in the ER lumen also conferred strong effects,
      despite the fact that replication occurs on the cytosolic side of the ER
      membrane. We conclude that the molecular integrity of NS4B is vital for HCV
      replication. Our results suggest that NS4B interacts with itself and with other
      viral and cellular factors, and may carry intrinsic capacities in order to allow
      replication.

PMID- 16806557
TI  - Histonefection: Novel and potent non-viral gene delivery.
AB  - Protein/peptide-mediated gene delivery has recently emerged as a powerful
      approach in non-viral gene transfer. In previous studies, we and other groups
      found that histones efficiently mediate gene transfer (histonefection).
      Histonefection has been demonstrated to be effective with various members of the
      histone family. The DNA binding domains and natural nuclear localisation signal
      sequences make histones excellent candidates for effective gene transfer. In
      addition, their positive charge promotes binding to anionic molecules and helps
      them to overcome the negative charge of cells that is an important barrier to
      cellular penetration. Histonefection appears to have particular promise in cancer
      gene transfer and therapy.

PMID- 16806558
TI  - Gastroretentive Accordion Pill: Enhancement of riboflavin bioavailability in
      humans.
AB  - The purpose of this study was to evaluate the ability of the Accordion Pill (AP),
      a novel controlled release gastroretentive unfolding dosage form (DF), to
      increase the bioavailability of riboflavin (RF) in humans. Three formulations
      containing 75 mg of RF and differing in release rate (immediate release (IR)
      capsule, AP#1, and AP#2) were administered with a low-calorie meal. Gastric
      residence time (GRT) of the AP was assessed by magnetic resonance imaging. Serial
      blood and urine samples were taken and assayed for RF. The AP demonstrated
      prolonged (up to 10.5 h) GRT in humans. Significant elevation in RF
      bioavailability (209+/-37%, mean+/-S.E.) was achieved by the AP#1 in comparison
      to the IR capsule. A correlation was established between the in-vitro release
      rates from DF and bioavailability of RF in humans, and it was modeled taking into
      account the saturable nature of RF absorption transport and its narrow absorption
      window (NAW) in the upper gastro-intestinal tract. It is anticipated that the AP
      will provide a valuable pharmaceutical solution to enhance therapy with NAW
      drugs.

PMID- 16806559
TI  - A patient with Werner syndrome and adiponectin gene mutation.
AB  - Werner syndrome is a premature aging disease characterized by genomic instability
      and increased cancer risk. Here, we report a 45-year-old diabetic man as the
      first Werner syndrome patient found to have an adiponectin gene mutation. Showing
      graying and loss of hair, skin atrophy, and juvenile cataract, he was diagnosed
      with Werner syndrome type 4 by molecular analysis. His serum adiponectin
      concentration was low. In the globular domain of the adiponectin gene, I164T in
      exon 3 was detected. When we examined effects of pioglitazone (15 mg/day) on
      serum adiponectin multimer and monomer concentrations using selective assays, the
      patient's relative percentage increased in adiponectin concentration was almost
      same as that in the 18 diabetic patients without an adiponectin mutation, but the
      absolute adiponectin concentration was half of those seen in diabetic patients
      treated with the same pioglitazone dose who had no adiponectin mutation. The
      response suggested that pioglitazone treatment might help to prevent future
      Werner syndrome-related acceleration of atherosclerosis. Present and further
      clinical relevant to atherosclerosis in this patient should be imformative
      concerning the pathogenesis and treatment of atherosclerosis in the presence of
      hypoadiponectinemia and insulin resistance.

PMID- 16806560
TI  - Efficacy of continuous glucose monitoring system (CGMS) to detect postprandial
      hyperglycemia and unrecognized hypoglycemia in type 1 diabetic patients.
AB  - BACKGROUND: To evaluate the efficacy of continuous glucose monitoring system
      (CGMS) to detect postprandial hyperglycemia and unrecognized hypoglycemia in type
      1 diabetes mellitus (DM1) patients. METHODS: We studied 46 patients
      (43.4%M/56.6%F), average age of 25.9+/-12.8 years, submitted to 72 h CGMS. It
      were analyzed: capillary glycemia (CG) and CGMS sensor's value, glycemic
      excursions, postprandial hyperglycemia, asymptomatic hypoglycemia and therapeutic
      management after CGMS. Correlation coefficient during hypo and hyperglycemia and
      sensitivity/specificity were determined. RESULTS: The mean capillary glucose
      values were 191.8+/-46.2mg/dl versus 190.9+/-42.1mg/dl by CGMS sensor, with no
      statistical difference by T-test (T=-0.6; p=0.79). The CGMS was significantly
      more efficient in detection of glycemic excursion than CG (p=0.001). The
      postprandial hyperglycemia was identified in 76.9% of diabetic patients and
      asymptomatic hypoglycemia was detected in 58.2% of these patients. The
      correlation coefficient presented no significance (p=0.16) during hypoglycemia
      versus during hyperglycemia (p=0.002). The CGMS sensor presented low sensitivity
      (79.1%) to detect hypoglycemia versus hyperglycemia (96.8%). CONCLUSIONS: The
      CGMS showed to be a good method to identify postprandial hyperglycemia, to
      improve therapeutics management and confirmed the low sensitivity of CGMS to
      detect unrecognized hypoglycemia in DM1 patients.

PMID- 16806561
TI  - Chronic renal failure in diabetic patients increases lipid risk factors for
      atherosclerosis.
AB  - Diabetic patients are at high risk of cardiovascular disease and the risk is
      amplified in the presence of nephropathy, which may be partially attributed to
      modifications in lipoproteins. Moreover, lipoprotein profile may be affected by
      incipient nephropathy, glomerulopathy, and mild or severe renal failure. The aim
      of our study was to evaluate whether chronic renal failure (CRF) changes
      lipoprotein profile and apo A-I urinary excretion in diabetic subjects with
      glomerulopathy in comparison with non-diabetic subjects with glomerulopathy and
      CRF. Diabetic (n=25) and non-diabetic (n=10) patients with glomerulopathy and CRF
      showed significantly higher LDL-cholesterol, non-HDL-cholesterol and HDL
      triglyceride levels than diabetic individuals without CRF (n=10). Arylesterase
      and paraoxonase activities did not show any difference between groups. Apo A-I
      could not be detected in urine samples from diabetic patients without CRF. All
      diabetic subjects with glomerulopathy and CRF who presented proteinuria above 6.5
      g/24 h showed detectable urinary apo A-I (range=13.1-61.0 mg/24 h). Similarly,
      all non-diabetic patients with glomerulopathy and CRF who had proteinuria above
      8.0 g/24 h also evidenced detectable apo A-I in urine (range=25.6-557.3 mg/24 h).
      Urinary apo A-I showed positive and significant correlations with urea (r=0.73,
      p<0.05) and proteinuria (r=0.97, p<0.0001), and a negative correlation with
      albumin plasma levels (r=-0.68, p<0.05). In conclusion, the presence of CRF in
      diabetic patients was associated with a more atherogenic lipoprotein profile.

PMID- 16806562
TI  - Perceptions of tuberculosis and health seeking behaviour in rural Inner Mongolia,
      China.
AB  - PURPOSE: This study aimed to explore perceptions of TB, and health care seeking
      pathways, among poor rural communities in Inner Mongolia. METHODOLOGY: Twenty
      focus group discussions (FGDs) were held and 105 farmers were included. Six
      hundred and fourteen randomly selected respondents were surveyed through
      interview questionnaire, in three poor rural counties with a high TB prevalence.
      MAIN FINDINGS: A substantial proportion of community members were unclear or
      misinformed as to how TB was transmitted. Sixty percent of respondents identified
      prolonged cough as a main symptom of TB, while only 40% perceived TB to be caused
      by 'close interaction with TB patient'. In addition, 70% could not afford TB
      treatment and fell into debt as a result of having to seek medical care. Social
      stigma associated with TB influenced marriage prospects and impeded important
      social interactions within the community. Respondents' perceptions of TB were
      associated with their socio-economic status. Women, young people, low-income
      groups and those with less education tended to be less knowledgeable about TB.
      All farmers in the study reported only seeking health care after they failed to
      treat themselves; and most of them then sought care from less qualified village
      level health care providers. Less educated people, low-income groups and old
      people were identified as less likely to seek care, or more likely to seek care
      at village level where it is cheaper. Both financial and structural barriers were
      found to stop farmers seeking health care. CONCLUSIONS AND POLICY IMPLICATIONS:
      Perceptions of TB and social stigma associated with the disease, together with
      socio-economic factors, shape the health seeking behaviour of poor farmers.
      Accessibility and affordability of TB health care issues should be dealt with
      through a multi-pronged approach, including health promotion in addition to
      expansion of the DOTS strategy and rural health insurance schemes.

PMID- 16806563
TI  - Hong Kong's health spending projections through 2033.
AB  - OBJECTIVE: To derive actuarial projection estimates of Hong Kong's total domestic
      health expenditure to the year 2033. METHODS: Disaggregating health expenditure
      by age, sex, unit cost and utilisation level, we estimated future health spending
      by projecting utilisation (by public/private, inpatient/outpatient care) to
      reflect demographic changes and associated increase in demand (from higher
      expectations and greater intensity of care), and then multiplying such by the
      projected unit costs (incorporating the impact of key cost drivers such as public
      expectations, technological changes and potential productivity gains) to obtain
      total expenditure estimates. RESULTS: The model was most sensitive to the excess
      health care price inflation rate, i.e. the annual price/cost growth of medical
      goods and services over and above per capita GDP growth. Population ageing and
      growth per se, without taking into account related technologic innovation for
      chronic conditions that particularly afflict older adults, contribute relatively
      little to overall spending growth. Given the model assumptions, it is possible to
      limit total health spending to below 10% of GDP by 2033, where the public share
      would gradually decline from the current 57% to between 46% and 49%. CONCLUSIONS:
      Expenditure control through global budgeting, technology assessment and demand
      side constraints should be considered although their effectiveness remains
      inconclusive.

PMID- 16806564
TI  - One perfect worm.
AB  - Recent studies show that local populations of the nematode Caenorhabditis elegans
      possess nearly as much genetic variation as that seen in existing worldwide
      collections. This suggests either wide-ranging migration and intense natural
      selection or recent dispersal, perhaps by human association. Either way, the
      effective population size of this ubiquitous model organism is unexpectedly
      small.

PMID- 16806565
TI  - To be or not to be toxic: aggregations in Huntington and Alzheimer disease.
AB  - Insoluble aggregated proteins in Alzheimer disease and Huntington disease might
      not be pathogenic. Human studies have poor correlations between aggregates and
      clinical disease or pathology in these disorders, whereas mouse models have
      demonstrated that neuronal loss can occur in the absence of detectable
      aggregates. Furthermore, aggregates can exist in the absence of disease pathology
      in mice or symptoms in humans. Recent research suggests that soluble protein
      fragments, not insoluble aggregated proteins, are the toxic species in these
      disorders.

PMID- 16806566
TI  - Is optimal gene order impossible?
AB  - Recent evidence suggests that yeast genes encoding proteins that are present in
      the same protein complex tend to be linked and to be co-expressed. More
      generally, we found that genes that are close to each other in the protein
      interaction network tend to be linked more often than expected and are often co
      expressed. Unexpectedly, we found that linked genes in network proximity have
      unusually high recombination rates. Because high recombination rates are
      associated with high rates of genome re-organization, our findings might explain
      why the clustering of genes in proximity in the network is such a weak effect:
      there could be a co-evolutionary cycle of physical linkage for co-expression,
      upwards modification of the recombination rate and concomitant break-up of a
      cluster. Under such a model an "optimal" gene order is never stable.

PMID- 16806567
TI  - Integrating patterns of polymorphism at SNPs and STRs.
AB  - Single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs) differ in
      mutation rate and mechanism. As a result of these differences, simultaneous
      consideration of polymorphism patterns at SNPs and STRs can provide insights that
      are difficult to obtain from analysis of either marker type in isolation. Here,
      we use coalescent simulations to model the opposing effects of contrasting
      mutational dynamics and of shared genealogical history on the correlation between
      polymorphism at linked SNPs and STRs. Results show that polymorphism patterns are
      correlated only weakly despite the shared underlying genealogy, underscoring the
      importance of divergent mutational processes. Examples illustrate how knowledge
      of these relationships could aid population genetic inference, indicating the
      need for thorough theoretical studies.

PMID- 16806568
TI  - Natural selection on gene expression.
AB  - Changes in genetic regulation contribute to adaptations in natural populations
      and influence susceptibility to human diseases. Despite their potential
      phenotypic importance, the selective pressures acting on regulatory processes in
      general and gene expression levels in particular are largely unknown. Studies in
      model organisms suggest that the expression levels of most genes evolve under
      stabilizing selection, although a few are consistent with adaptive evolution.
      However, it has been proposed that gene expression levels in primates evolve
      largely in the absence of selective constraints. In this article, we discuss the
      microarray-based observations that led to these disparate interpretations. We
      conclude that in both primates and model organisms, stabilizing selection is
      likely to be the dominant mode of gene expression evolution. An important
      implication is that mutations affecting gene expression will often be deleterious
      and might underlie many human diseases.

PMID- 16806569
TI  - Development of quantification software using model-based segmentation of left
      ventricular myocardium in gated myocardial SPECT.
AB  - Gated myocardial single photon emission computed tomography (SPECT) is being used
      for the diagnosis of coronary artery diseases. In this study, we developed new
      software for the quantification of volumes and ejection fraction (EF) on the
      gated myocardial SPECT data using a cylindrical model. Volumes and EF by
      developed software were validated by comparing with those quantified by
      quantitative gated SPECT (QGS) software. Cylinder model for left ventricular
      myocardium was used to eliminate background activity and count profiles across
      the myocardium were fitted to the Gaussian curve to determine the endocardial and
      epicardial boundary. End-diastolic volume (EDV), end-systolic volume (ESV) and EF
      were calculated using this boundary information. Gated myocardial SPECT was
      performed in 83 patients. EDV, ESV and EF values estimated using present method
      were compared to those obtained using the commercialized software QGS, and
      reproducibility in the parameter estimation was assessed. EF, EDV and ESV
      obtained using two methods were correlated well (correlation coefficients = 0.96,
      0.96 and 0.98). The correlation between the parameters repetitively estimated
      from the same data set by an operator was very high (correlation coefficients =
      0.96, 0.99 and 0.99 for EF, EDV and ESV). On the repeated acquisition,
      reproducibility was also high with correlation coefficients of 0.89, 0.97 and
      0.98. The present software will be useful for the development of new parameters
      for describing the perfusion and function of the LV.

PMID- 16806570
TI  - MedDietScore: a computer program that evaluates the adherence to the
      Mediterranean dietary pattern and its relation to cardiovascular disease risk.
AB  - Mediterranean dietary traditions have long been associated with lower mortality
      rates and better health status. The Mediterranean dietary pattern has become
      customary to be represented in the form of a pyramid, the base of which refers to
      foods which are suggested to be consumed most frequently and the top of the
      pyramid to those foods consumed rarely. Recently, an index (diet score) that
      estimates the adherence level to Mediterranean diet was developed and associated
      with cardiovascular disease risk and biomarkers. In this work we present a
      computer program that can easily calculate this diet score, as well as its
      association with cardiovascular disease risk. The application of this software to
      the general public might be a useful tool for the reduction of the disease burden
      related with nutritional habits at population level.

PMID- 16806571
TI  - Preprocessing RR interval time series for heart rate variability analysis and
      estimates of standard deviation of RR intervals.
AB  - Heart rate variability is concerned with the analysis of the fluctuations in the
      interval between heart beats known as RR intervals. The long time RR time series
      obtained suffer from non-stationarity and the presence of ectopic beats, which
      prevents extraction of useful statistical information. The paper describes a
      wavelet-based technique for trend removal and a nonlinear filter to remove
      ectopic beats. This attempts to correct the limitations observed in a recent
      advanced heart rate toolkit [J. Niskanen, M.P. Tarvainen, P.O. Ranta-aho P.A.
      Karjalainen, Software for advanced HRV analysis, Comput. Meth. Prog. Biomed.,76
      (2004) 73-81] when preprocessing. The results are encouraging. The preprocessed
      data are then used to obtain the standard deviation of RR interval time series
      (SDRR) of 15 healthy patients and 15 patients suffering from congestive heart
      failure. The results demonstrate the importance of preprocessing. The analysis
      show that the SDRR values of congestive heart failure patients are depressed
      compared to the healthy group.

PMID- 16806572
TI  - Glucocorticoid receptor expression in advanced non-small cell lung cancer:
      clinicopathological correlation and in vitro effect of glucocorticoid on cell
      growth and chemosensitivity.
AB  - The current study aimed to immunohistochemically examine the tumor
      glucocorticoids receptor (GR) expression in patients with advanced non-small cell
      lung cancer (NSCLC) and to examine the effect of glucocorticoids (GCs) on the in
      vitro NSCLC cells growth and chemosensitivity. High GR expression was detected in
      51% of the tumor specimens. The difference in tumor GR expression was not
      associated with cell type, gender, age, or stage. The outcome was significantly
      superior for patients whose tumor showed high GR expression compared to those
      with either low expression or non-expression. The median progression-free
      survival was 8.0 versus 5.6 months (p=0.039) and overall survival was 18.1 versus
      10.2 months, (p=0.003), respectively. Almost all these patients have received GC
      as antiemetics or allergic preventive treatment during chemotherapy courses,
      therefore, the effect of GC on the chemosensitivity in vivo was not evaluable.
      However, in vitro cytotoxicity assay showed that dexamethasone (DEX) had
      heterogeneous effects on the growth and chemosensitivity of the NSCLC cell lines.
      These findings suggest that tumor samples express high levels of GR in about half
      of the patients with advanced NSCLC, and this high expression of GR may be
      associated with better outcome. The effect of GC treatment on the
      chemosensitivity in NSCLC patients remains to be established.

PMID- 16806573
TI  - A phase I and pharmacological study of amrubicin and topotecan in patients of
      small-cell lung cancer with relapsed or extensive-disease small-cell lung cancer.
AB  - Cisplatin-based chemotherapy is considered to be a standard treatment in patients
      with relapsed or extensive-disease (ED) small-cell lung cancer (SCLC), the
      survival benefit remains modest. Relapsed or ED-SCLC patients were enrolled.
      Topotecan and amrubicin were administered on Days 1-5 and on Days 3-5,
      respectively. Nine patients received a total of 24 cycles. Since all three
      patients experienced dose-limiting toxicity (grade 4 neutropenia lasting for more
      than 4 days, grade 3 febrile neutropenia, and grade 4 thrombocytopenia) at the
      third dose level (topotecan: 0.75 mg/m2, amrubicin 40 mg/m2), the maximum
      tolerated dose was determined to be this dose level. Objective response was
      observed in six patients (67%). The maximum concentration (Cmax) and area under
      the plasma concentration-time curve (AUC) of amrubicin increased in a dose
      dependent manner. Amrubicin did not influence the pharmacokinetics of topotecan.
      The Cmax and AUC of amrubicin were correlated with the duration of grade 4
      neutropenia. The mean Cmax of topotecan on day 2 in responders (22.9+/-3.6) was
      significantly higher than that in non-responders (10.9+/-0.4). This phase I study
      showed the safety and activity of two-drug combination of amrubicin and topotecan
      in patients with relapsed or ED-SCLC.

PMID- 16806574
TI  - The animal cultures debate.
AB  - Recent interest in animal cultures has been fuelled by high-profile reports of
      intra- and interpopulation differences in the behavioural repertoires of primates
      and cetaceans, consistent with the existence of socially learned traditions.
      Several studies have mapped spatial differences in behaviour, revealing a mosaic
      of behavioural phenotypes within species. The dominant current approach attempts
      to determine whether this is cultural variation by excluding asocial learning,
      ecological or genetic factors. However, claims of animal cultures remain
      controversial because such comparisons are subject to weaknesses; thus, new
      approaches to isolating the influence of culture on behaviour are required. Here
      we suggest that, rather than attributing behaviour to explanatory categories,
      researchers would often be better advised to partition variance in behaviour to
      alternative sources.

PMID- 16806575
TI  - Functional evo-devo.
AB  - Functional factors such as optimal design and adaptive value have been the
      central concern of evolutionary biology since the advent of the New Synthesis. By
      contrast, evolutionary developmental biology (evo-devo) has concentrated
      primarily on structural factors such as the ways in which body parts can be
      built. These different emphases have stood in the way of an integrated
      understanding of the role of development in evolution. Here, we try to bridge
      this gap by outlining the relevance of functional factors in evo-devo. We use
      modularity and the view of development as a flexible evolutionary system to
      outline a unified perspective that includes both structural and functional
      aspects.

PMID- 16806576
TI  - Using ecosystem engineers to restore ecological systems.
AB  - Ecosystem engineers affect other organisms by creating, modifying, maintaining or
      destroying habitats. Despite widespread recognition of these often important
      effects, the ecosystem engineering concept has yet to be widely used in
      ecological applications. Here, we present a conceptual framework that shows how
      consideration of ecosystem engineers can be used to assess the likelihood of
      restoration of a system to a desired state, the type of changes necessary for
      successful restoration and how restoration efforts can be most effectively
      partitioned between direct human intervention and natural ecosystem engineers.

PMID- 16806577
TI  - Towards a more plant physiological perspective on soil ecology.
AB  - Soil respiration almost balances carbon fixation by terrestrial photosynthesis
      and exceeds all anthropogenic carbon emissions by an order of magnitude, yet we
      lack precise knowledge of the sources of, and controls upon, the release of
      carbon dioxide from soils. Here, we discuss the increasing evidence that half of
      this carbon release is from living plant roots, their mycorrhizal fungi and other
      root-associated microbes, and that this release is driven directly by recent
      photosynthesis. The new studies challenge the widespread view that soil activity
      is dominated by decomposer organisms using older detrital material and that root
      litter inputs equal those of aboveground litter. The new observations emphasize
      the physiological continuity and dynamic interdependence of the plant-microbe
      soil system and highlight the need for closer cooperation between plant and soil
      scientists.

PMID- 16806578
TI  - Capability and limitations of first-order and diffusion approaches to describe
      long-term sorption of chlortoluron in soil.
AB  - This paper compares the capability of a first-order and a spherical diffusion
      model to describe and predict long-term sorption and desorption processes of
      chlortoluron in two soils. Chlortoluron sorption was investigated at different
      time scales utilizing one rate experiment (120 days) and two sorption/desorption
      experiments. Experimental periods for sorption and desorption were set to 1 day
      (five desorption steps) and 30 days (three desorption steps), respectively. Upon
      fitting, the two models satisfactorily described the whole set of data. The
      spherical diffusion model performed better than the first-order model. We then
      tested the predictive capability of the models by predicting 30-day
      sorption/desorption data using kinetic parameters fitted on 1-day
      sorption/desorption data only. While the spherical diffusion model was able to
      predict the 30-day data set, the first-order model failed completely. Fitting
      both models to subsets of the data corresponding to different experimental time
      scales revealed that the rate parameter as well as the Freundlich coefficient of
      the first-order model are strongly time-dependent--a property that is not shared
      by parameters of the spherical diffusion model. The apparent stability of the
      spherical diffusion model with regard to time dependency of its parameters
      indicates that sorptive uptake may be diffusion-controlled. This also explains
      the models greater predictive power across different time scales compared to the
      first-order model. Finally, we investigate the suitability of solute class
      specific log-linear relationships between the first-order rate parameter and the
      Freundlich coefficient presented by earlier researchers in the light of the time
      dependency observed for the parameters of the first-order model.

PMID- 16806579
TI  - An evolutionary perspective on dieting.
AB  - We examine the principal features of dieting using an evolutionary perspective,
      which sheds light on certain anomalies while raising other interesting questions.
      We focus on (a) the reasons that dieters give for dieting, (b) the difficulty of
      dieting, and (c) the apparent opposition between the proclivities toward self
      indulgence and self-control. We propose that while self-indulgence and self
      control both serve adaptive functions, these evolved tendencies are naturally
      triggered by different ecological challenges. Implications for dieting in an
      ecology of plenty are explored.

PMID- 16806580
TI  - Evolutionary and anthropological perspectives on optimal foraging in obesogenic
      environments.
AB  - The nutrition transition has created an obesogenic environment resulting in a
      growing obesity pandemic. An optimal foraging approach provides cost/benefit
      models of cognitive, behavioral and physiological strategies that illuminate the
      causes of caloric surfeit and consequent obesity in current environments of
      abundant food cues; easy-access and reliable food patches; low processing costs
      and enormous variety of energy-dense foods. Experimental and naturalistic
      observations demonstrate that obesogenic environments capitalize on human
      proclivities by displaying colorful advertising, supersizing meals, providing
      abundant variety, increasing convenience, and utilizing distractions that impede
      monitoring of food portions during consumption. The globalization of fast foods
      propels these trends.

PMID- 16806581
TI  - Estrus variation in anxiolytic-like effects of intra-lateral septal infusions of
      the neuropeptide Y in Wistar rats in two animal models of anxiety-like behavior.
AB  - Anxiolytic-like effects of intra-lateral septal infusions of the neuropeptide Y
      (NPY) were assessed during several estrus phases in Wistar rats tested in two
      animal models of anxiety-like behavior. In a conflict operant test, results
      showed that during late proestrus, intra-lateral septal nuclei infusions of NPY
      (1.0 microg/microl, P<0.05; 2.0 microg/microl, P<0.05; 2.5 microg/microl, P<0.05)
      increased the number of immediately punished responses. During metestrus-diestrus
      only the highest doses of NPY (2.5 microg/microl, P<0.05) increased the number of
      immediately punished reinforcers. In the elevated plus-maze test, results showed
      that during late proestrus, intra-lateral septal nuclei infusions of NPY (1.0
      microg/microl, P<0.05; 2.0 microg/microl, P<0.05) produced anxiolytic-like
      actions. During metestrus-diestrus only the highest doses of NPY (2.0
      microg/microl, P<0.05) produced anxiolytic-like actions. Neither NPY nor estrus
      phases significantly modified the number of closed arms entries in the elevated
      plus-maze test. It is concluded that anxiolytic-like effects of NPY vary within
      the estrus cycle in Wistar rats.

PMID- 16806582
TI  - N-terminal parathyroid hormone-related peptide hyperpolarizes endothelial cells
      and causes a reduction of the coronary resistance of the rat heart via
      endothelial hyperpolarization.
AB  - Parathyroid hormone-related peptide (PTHrP) is known to be a strong vasorelaxant
      peptide. The mechanisms by which PTHrP reduces the coronary resistance of the rat
      heart have not been worked out but seem to be independent of the classical
      PTH/PTHrP receptor-mediated, cAMP-dependent effect. In this study we hypothesized
      that PTHrP reduces the coronary resistance of the rat heart via endothelial cell
      hyperpolarization. Isolated microvascular endothelial cells from rat heart were
      incubated with PTHrP(1-36), and changes in the membrane potential were recorded
      via DiBAC fluorescence. Cells exposed to PTHrP showed a hyperpolarization of
      approximately 7mV. In the isolated Langendorff preparation, PTHrP-dependent
      vasodilatation of l-nitro-arginine-exposed hearts was abolished under
      depolarizing conditions (high potassium). Denudation of the endothelial cell
      layer significantly impaired the vasodilatory effect of PTHrP. In the presence of
      H89 (a cAMP/protein kinase A pathway antagonist) and indomethacin (a
      cyclooxygenase inhibitor), PTHrP dilated the vessels. In conclusion, PTHrP
      exerted a nitric oxide-independent vasodilatory effect that depends on
      endothelial cell hyperpolarization.

PMID- 16806583
TI  - Effects of the antimicrobial peptide BMAP-27 in a mouse model of obstructive
      jaundice stimulated by lipopolysaccharide.
AB  - An experimental study was designed to investigate the efficacy of BMAP-27, a
      compound of the cathelicidin family, in neutralizing Escherichia coli 0111:B4
      lipopolysaccharide (LPS) in bile duct-ligated mice. Main outcome measures were:
      endotoxin and TNF-alpha concentrations in plasma, evidence of bacterial
      translocation in blood and peritoneum, and lethality. Adult male BALB/c mice were
      injected intraperitoneally with 2 mg/kg E. coli 0111:B4 LPS 1 week after sham
      operation or bile duct ligation (BDL). Six groups were studied: sham with
      placebo, sham with 120 mg/kg tazobactam-piperacillin (TZP), sham with 1 mg/kg
      BMAP-27, BDL with placebo, BDL with 120 mg/kg TZP, and BDL with 1mg/kg BMAP-27.
      After LPS, TNF-alpha plasma levels were significantly higher in BDL mice compared
      to sham-operated animals. BMAP-27 achieved a significant reduction of plasma
      endotoxin and TNF-alpha concentration when compared with placebo- and TZP-treated
      groups. On the other hand, both TZP and BMAP-27 significantly reduced the
      bacterial growth compared with saline treatment. Finally, LPS induced 60% and 55%
      lethality in BDL placebo- and TZP-treated treated mice and no lethality in sham
      operated mice, while only BMAP-27 significantly reduced the lethality to 10%. In
      light of its dual antimicrobial and anti-endotoxin properties, BMAP-27 could be
      an interesting compound to inhibit bacterial translocation and endotoxin release
      in obstructive jaundice.

PMID- 16806584
TI  - Melanocortin-4 receptor-mediated inhibition of apoptosis in immortalized
      hypothalamic neurons via mitogen-activated protein kinase.
AB  - The melanocortin-4 receptor (MC4R) is a seven transmembrane member of the
      melanocortin receptor family. The GT1-1 cell line exhibits endogenous expression
      of MC4R. In this study, GT1-1 cells were used to study MC4R signaling pathways
      and to examine the effects of melanocortin receptor agonist NDP-MSH on apoptosis.
      MC4R mRNA expression was demonstrated by RT-PCR. Functional melanocortin receptor
      expression was implied by specific binding of NDP-MSH and cAMP production. NDP
      MSH-stimulated GnRH release in a dose-dependent manner. Serum deprivation-induced
      apoptosis in GT1-1 cells, and the NDP-MSH inhibited this effect. The melanocortin
      receptor antagonist SHU9119 blocked the antiapoptotic actions of NDP-MSH, and the
      MAP kinase inhibitor PD98059 significantly attenuated the antiapoptotic effect.
      NDP-MSH-stimulated ERK1/2 phosphorylation in a dose-dependent manner. ERK1/2
      phosphorylation could be abolished by SHU9119. In GT1-1 cells, melanocortin
      receptor activation causes ERK1/2 phosphorylation. In these cells, MC4R
      activation is also associated with antiapoptotic effects.

PMID- 16806585
TI  - Release of glutamate by the embryonic spinal motoneurons of rat positively
      regulated by acetylcholine through the nicotinic and muscarinic receptors.
AB  - It has been shown that mature neurons in adult vertebrates can co-express
      glutamate and acetylcholine. Furthermore, interactions at the synaptic level have
      been demonstrated. In a previous study we found that also motoneurons at early
      embryonic stages, thus well prior to synapse formation, release acetylcholine,
      and that glutamate increases this release. We now report the existence of a
      glutamate release from embryonic motoneurons and the increase of glutamate
      release by acetylcholine. This effect is mediated by nicotinic and muscarinic
      cholinergic receptors present on embryonic motoneurons. Using conditions of
      partial or total depletion of calcium, we show that the glutamate release has two
      components: one is calcium-dependent and the other calcium-independent.
      Furthermore, we show that extracellular glutamate can be taken up by motoneurons,
      probably via the neuronal glutamate transporter EAAC1, which we find to be
      expressed at this stage. Monitoring of the glutamate release kinetics showed that
      extracellular glutamate concentration reached a steady-state level, strongly
      suggesting the establishment of equilibrium between glutamate release and uptake.
      Altogether, these results support the idea that glutamate can act as a
      neurotransmitter in embryonic motoneurons. We hypothesise that, glutamate acts as
      a regulator of motoneuron maturation and spinal cord development.

PMID- 16806586
TI  - Neuroprotective effects of iron chelator Desferal on dopaminergic neurons in the
      substantia nigra of rats with iron-overload.
AB  - The aim of the present study was to investigate whether the iron chelator
      Desferal prevents the degeneration of dopaminergic neurons in the substantia
      nigra (SN) induced by iron-overload in rats. Using fast cyclic voltammetry,
      tyrosine hydroxylase (TH) immunohistochemistry, Perls' iron staining, and high
      performance liquid chromatography-electrochemical detection, we measured the
      degeneration of dopaminergic neurons and increased iron content in the SN of rats
      overloaded with iron dextran and assessed the effects of treatment with Desferal.
      The results showed that iron dextran overload increased the iron content in the
      SN, decreased dopamine release and content, and reduced the numbers of TH
      immunoreactive neurons. Treatment with Desferal prevented the increased iron
      content in the SN. As a result, dopamine release and content remained at almost
      normal levels, while the numbers of TH-immunoreactive neurons remained at control
      values. This study suggests that the iron chelator Desferal is neuroprotective
      against iron-overload, so iron chelators that can cross the blood-brain barrier
      may have the potential to treat cases where abnormal iron accumulation in the
      brain is associated with the degenerative processes, as in Parkinson's disease.

PMID- 16806587
TI  - Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats.
AB  - Rodent models of cognitive aging routinely use spatial performance on the water
      maze to characterize medial temporal lobe integrity. Water maze performance is
      dependent upon this system and, as in the aged human population, individual
      differences in learning abilities are reliably observed among spatially
      characterized aged rats. However, unlike human aging in which cognitive deficits
      rarely occur in isolation, few non-spatial learning deficits have been identified
      in association with spatial impairment among aged rats. In this study, a subset
      of male aged Fischer 344 rats was impaired both in water maze and odor
      discrimination tasks, whereas other aged cohorts performed on par with young
      adult rats in both settings. The odor discrimination learning deficits were
      reliable across multiple problems. Moreover, these deficits were not a
      consequence of anosmia and were specific to olfactory learning, as cognitively
      impaired aged rats performed normally on an analogous non-olfactory
      discrimination task. These are among the first data to describe an aging model in
      which individual variability among aged rat cognition occurs across two
      independent behavioral domains.

PMID- 16806588
TI  - Neuroprotective effect of Coenzyme Q10 on ischemic hemisphere in aged mice with
      mutations in the amyloid precursor protein.
AB  - This study was designed to test whether Coenzyme Q10 (CoQ10) supplementation has
      neuroprotective effect in aged, double-transgenic amyloid precursor protein
      (APP)/presenilin 1 (PS1), single transgenic APP and PS1 mice exposed to ischemic
      injury of the brain. Forty-eight mice (12 each of APP/PS1, APP, PS1 and wild
      type) were studied. Half of each genotype groups (n=6 per group) was treated with
      CoQ10 (1200 mg/kg/day) after ischemic injury and the other half with placebo.
      Magnetic resonance (MR) images were used to measure the volume of induced
      infarction (IFV), as well as the volume of the hemispheres and hippocampi.
      Significantly greater volumes of infarction and lesser volumes of
      hemisphere/hippocampus on the ischemic side were observed in APP/PS1 and APP mice
      than in PS1 and wild-type mice. This is consistent with amplification of the
      effect of ischemia in APP carriers. After 28 days of CoQ10 treatment, APP/PS1 or
      APP mutations have smaller infarct volumes, while the volumes of hemisphere and
      hippocampus on the infarcted side were larger than those treated with placebo. No
      differences between CoQ10- and placebo-treated groups in volumes of infarct,
      hemisphere and hippocampus were observed in PS1 and wild-type mice. We conclude
      that CoQ10 has a protective effect on the brain from infarction and atrophy
      induced by ischemic injury in aged and susceptible transgenic mice.

PMID- 16806589
TI  - Exploring QSAR on 3-aminopyrazoles as antitumor agents for their inhibitory
      activity of CDK2/cyclin A.
AB  - Chemical inhibitors of cyclin-dependent kinases have great therapeutic potential
      against various proliferative and neurodegenerative disorders. The pharmacophoric
      requirement of 3-aminopyrazole, inhibitors of CDK2/cyclin A as antitumor agents
      was explored. QSAR study was performed using ETSA index, RTSA index, indicator
      parameters and atomic charges to consider quantitatively the effect of the
      structural variation on the antitumor activity of 3-aminopyrazole. Result showed
      that atom number 5 is important for the activity. It plays some electronic roles
      in the interaction of these compounds with enzymes as well as assumed to be
      involved through the dispersive/van der Waals interactions with enzyme. Presence
      of meta substitutions on the phenyl ring indicate the detrimental effects towards
      the activity. The presence of substituted biphenyl/2-thenyl phenyl at R1 are
      favorable towards the activity. QSAR study also indicates that with increasing
      the electronegativity of oxygen at position 8, the activity increases.

PMID- 16806590
TI  - Pharmacological activity and hydrolysis behavior of novel ibuprofen
      glucopyranoside conjugates.
AB  - Novel ester prodrugs (II, III and IV) of ibuprofen (I) were synthesized using
      alpha-methyl, ethyl and propyl glucopyranoside as promoieties and tested for
      their anti-inflammatory, analgesic and ulcerogenic activities. Study of their
      chemical hydrolysis in aqueous buffer (pH 3.0-10.0) showed that these compounds
      acted as true prodrugs of ibuprofen, giving the ibuprofen and alkyl
      glucopyranoside. Additionally, all the derivatives studied did cleave rapidly
      inside the biological system and on oral administration did elicit a
      pharmacological profile quite similar to that of ibuprofen, but, unlike this
      drug, they displayed reduced gastric ulceration. In conclusion, these alkyl
      glucopyranoside esters have promising properties as prodrugs for oral delivery of
      ibuprofen.

PMID- 16806591
TI  - [Cholinesterase inhibitor therapy in long term care settings].
AB  - PURPOSE: Cholinesterase Inhibitors (ChEIs) have proven efficacy in outpatients
      with mild to moderate Alzheimer's Disease (AD). The benefits of maintaining this
      treatment once patients are institutionalised remain controversial. The aim of
      this study was to present current therapeutic strategies regarding ChEIs use in
      long-term care settings (LTC). METHODS: A multicentric, retrospective,
      observational study was conducted on currently available ChEIs (donezepil,
      rivastigmine, galantamine) prescribed in LTC. Data were obtained from medical
      records. Judgement was based on three criteria: ChEIs indication, follow-up, and
      justification for maintenance of treatment. RESULTS: Among the 1,373 patients
      evaluated, 6% (N=81) were receiving ChEIs. They represented various stages of the
      disease, with cognitive and functional decline ranging from severe (18%) to very
      mild (10%). Among patients receiving ChEIs, 29% met neither the indication for
      which these drugs were approved, nor professional guidelines. Patient evaluation
      at entry was of high quality, with 90% of records including cognitive, functional
      and behavioural evaluation. Follow-up evaluations were weaker, with at least one
      assessment domain missing in 40% of the medical records. ChEIs treatment was
      maintained, although almost half of patients experienced a worsening of their
      clinical state. CONCLUSION: This study shows that follow-up of institutionalised
      patients receiving ChEIs could be improved. While treatment maintenance seems to
      be the rule, it should be questioned on ethical, efficacy, and economic grounds.
      The rationale for use and discontinuation of these therapeutic strategies in
      institutional settings requires urgent review.

PMID- 16806592
TI  - [Carcinoma cuniculatum: an uneasy diagnosis to suspect in case of chronic
      osteomyelitis with unsuccessful outcome despite appropriate antibiotic therapy].
AB  - INTRODUCTION: The clinical and histological features of cuniculatum carcinoma
      (CC) are often misleading. CASE REPORT: We report a case of CC of the foot, which
      was misdiagnosed as osteomyelitis for a two year period and which relapsed 2
      months after complete resection. DISCUSSION: The CC has to be evoked in patients
      with chronic osteomyelitis and torpid wound. The anatomopathologist needs to be
      aware of the suspected diagnosis.

PMID- 16806593
TI  - [Prevalence of Epstein-Barr virus in Sjogren's syndrome in Tunisia].
AB  - PURPOSE: The cause of Sjogren's syndrome is unclear. Several studies suggested
      the role of Epstein-Barr virus (EBV) in the pathogenesis of this syndrome, but
      this always remains a subject of numerous controversies. The purpose of this
      study was to evaluate the prevalence of EBV in Sjogren's syndrome in Tunisia.
      METHODS: A series of 31 paraffin-embedded biopsies of salivary glands from
      patients with Sjogren's syndrome were studied in comparison with 19 control
      glands. EBV was investigated by PCR, EBERs in situ hybridization and by
      immunohistochemistry for the detection of LMP1, EBNA2 and ZEBRA. RESULTS: EBV DNA
      was detected by PCR in 3 of 22 PCR beta-globin positive Sjogren's syndrome cases
      (13.6%) and in 2 of 17 PCR beta-globin positive control glands (11.7%); in situ
      hybridization positivity was noted in rare lymphocytes in the 3 EBV positive
      cases of Sjogren's syndrome, but not in control glands; immunohistochemical study
      was negative in all cases. CONCLUSION: EBV infection does not appear to play a
      significant role in the pathogenesis of Sjogren's syndrome in Tunisia.

PMID- 16806594
TI  - [Chronic calcifying pancreatitis revealing a primary hyperparathyroidism].
AB  - INTRODUCTION: The association of pancreatitis and hyperparathyroidism is rare.
      CASE RECORD: A 41-year-old man had consulted for a strong abdominal pain reliant
      to a chronic calcifying pancreatitis. A major hypercalcaemia led to a primary
      hyperparathyroidism diagnosis. The evolution was favourable after parathyroid
      adenoma surgery. DISCUSSION: The hypercalcaemia activate the transformation of
      trypsinogen into trypsin which is toxic for the pancreas. The role of parathyroid
      hormone remains unclear.

PMID- 16806596
TI  - Transmissibility and mortality impact of epidemic and pandemic influenza, with
      emphasis on the unusually deadly 1951 epidemic.
AB  - There are important gaps in our current understanding of the influenza virus
      behavior. In particular, it remains unclear why some inter-pandemic seasons are
      associated with unusually high mortality impact, sometimes comparable to that of
      pandemics. Here we compare the epidemiological patterns of the unusually deadly
      1951 influenza epidemic (A/H1N1) in England and Wales and Canada with those of
      surrounding epidemic and pandemic seasons, in terms of overall mortality impact
      and transmissibility. Based on the statistical and mathematical analysis of vital
      statistics and morbidity epidemic curves in these two countries, we show that the
      1951 epidemic was associated with both higher mortality impact and higher
      transmissibility than the 1957 and 1968 pandemics. Surprisingly in Liverpool,
      considered the 'epicenter' of the severe 1951 epidemic, the mortality impact and
      transmissibility even surpassed the 1918 pandemic.

PMID- 16806597
TI  - Analysis of a delayed epidemic model with pulse vaccination and saturation
      incidence.
AB  - Pulse vaccination is an important strategy for the elimination of infectious
      diseases. An SEIRS epidemic model with time delays and pulse vaccination is
      formulated in this paper. Using the discrete dynamical system determined by the
      stroboscopic map, we obtain the exact infection-free periodic solution of the
      impulsive epidemic system and prove that the infection-free periodic solution is
      globally attractive if the vaccination rate is larger than theta*. Moreover, we
      show that the disease is uniformly persistent if the vaccination rate is less
      than theta*. The permanence of the model is investigated analytically. Our
      results indicate that a long latent period of the disease is sufficient condition
      for the extinction of the disease.

PMID- 16806598
TI  - Multivalent DNA vaccine protects mice against pulmonary infection caused by
      Pseudomonas aeruginosa.
AB  - For efficacious vaccine development against Pseudomonas aeruginosa (P.
      aeruginosa), the immunogenicity of multivalent DNA vaccine was evaluated. Three
      different plasmids each targeting a fusion of outer membrane proteins
      (OprF/OprI), a protein regulating type III secretion system (PcrV), or an
      appendage (PilA) were prepared and mice were immunized with single (monovalent)
      or a combination of these plasmids (multivalent) via intramuscular
      electroporation (imEPT) or gene gun. Immunization with multivalent DNA vaccine
      via imEPT induced the most potent protection against lethal pneumonia. Although
      the serum levels of IgG binding to whole bacteria cells were comparable between
      groups, the strongest immune protection was associated with the serum levels of
      Th1-dominated multivalent IgG, the bronchoalveolar levels of macrophage
      inflammatory protein 2 (MIP-2) and IFN-gamma, and the number of neutrophils and
      macrophages in the bronchoalveolar lavage following intranasal challenge. These
      results implied the possible clinical application of multivalent DNA vaccine
      against P. aeruginosa.

PMID- 16806599
TI  - Self-mimicking autoimmune domains of hepatitis C virus core antigen.

PMID- 16806600
TI  - Immune responses in mice induced by prime-boost schemes of the Plasmodium
      falciparum apical membrane antigen 1 (PfAMA1)-based DNA, protein and recombinant
      modified vaccinia Ankara vaccines.
AB  - The apical membrane antigen 1 (AMA1) of malaria parasites is a leading vaccine
      candidate. Its expression in merozoites and sporozoites and its importance for
      erythrocyte and hepatocyte invasion underline the significance of both humoral
      and cellular immunities against this antigen in malaria protection. We have
      generated a DNA construct and a recombinant poxvirus (rMVA) for expressing the
      Plasmodium falciparum AMA1 ectodomain, produced recombinant AMA1 protein (rAMA1)
      and evaluated their antigenicity in mice using single and combinatory vaccine
      schemes. Our results showed that although vaccinations of mice by either DNA or
      rMVA alone did not yield high antibody responses, they had primed significant
      numbers of rAMA1-responsive splenocytes. Under heterologous prime-boost schemes,
      priming with DNA followed by boosting with rMVA or rAMA1 protein resulted in a
      significant increase in antibody titers. In addition, the antibody titers to AMA1
      appeared to be correlated with the levels of inhibition of merozoite invasion of
      erythrocytes in vitro. Furthermore, different prime-boost schemes resulted in
      different AMA1-specific antibody isotype (IgG1/IgG2a) ratios, providing us with
      an indication about Th1 or Th2 responses the vaccination regimens have induced.
      This study has yielded useful information for further in vivo evaluation of the
      suitability and effectiveness of the heterologous prime-boost strategy in AMA1
      vaccination.

PMID- 16806601
TI  - Towards improved influenza A virus surveillance in migrating birds.
AB  - The last decade has seen a marked increase in highly pathogenic avian influenza
      (HPAI) outbreaks around the world. This increase and the zoonotic potential of
      some of the HPAI viruses are of great concern to animal and public health as well
      as biodiversity. It is now well recognized that global influenza virus
      surveillance in wild birds can play a key role in the early recognition of and
      preparation for these threats. Here we summarize the most important results from
      our wild bird surveillance studies in Northern Europe over the last 8 years and
      conclude that surveillance studies in wild birds are indeed useful to generate
      prototypic vaccine candidates and to design and evaluate diagnostic tests, prior
      to the occurrence of outbreaks in animals and humans. Through this 8-year
      experience we also identified gaps in our knowledge on influenza A viruses and
      their natural hosts which may help to assist in the design of improved
      surveillance studies. This is particularly relevant if wild bird surveillance
      studies are used as an "early warning system" for the arrival of the H5N1 HPAI
      virus in a country or region and to assess the risk posed by these viruses in
      general.

PMID- 16806602
TI  - Immune responses elicited by bacterial minicells capable of simultaneous DNA and
      protein antigen delivery.
AB  - Recent events surrounding emerging infectious diseases, bioterrorism and
      increasing multidrug antibiotic resistance in bacteria have drastically increased
      current needs for effective vaccines. Many years of study have shown that live,
      attenuated pathogens are often more effective at delivering heterologous protein
      or DNA to induce protective immune responses. However, these vaccine carriers
      have inherent safety concerns that have limited their development and their use
      in many patient populations. Studies using nonliving delivery mechanisms have
      shown that providing both protein antigen and DNA encoding the antigen to an
      individual induces an improved, more protective immune response but rarely, if
      ever, are both delivered simultaneously. Here, non-replicating bacterial
      minicells derived from a commensal E. coli strain are shown to effectively induce
      antigen-specific immune responses after simultaneous protein and DNA delivery.
      These data demonstrate the potential use of achromosomal bacterial minicells as a
      vaccine carrier.

PMID- 16806603
TI  - The impact of routine infant immunization with Haemophilus influenzae type b
      conjugate vaccine in Malawi, a country with high human immunodeficiency virus
      prevalence.
AB  - Malawi has extreme poverty and a high-human immunodeficiency virus (HIV)
      prevalence. Following Haemophilus influenzae type b (Hib) conjugate vaccine
      introduction during 2002, we evaluated vaccine impact by reviewing hospital
      surveillance data for acute bacterial meningitis in Blantyre district among
      children age 1-59 months admitted during 1997-2005. Documented annual Hib
      meningitis incidence rates decreased from 20-40/100,000 to near zero among both
      rural and urban residents despite no change in pneumococcal meningitis incidence
      rates. Before vaccine introduction, an average of 10 children/year had Hib
      meningitis and HIV infection compared to 2/year during 2003-2004 and none during
      2005. Vaccine effectiveness was high following two or more doses of vaccine. The
      most urgent future need is for a sustainable routine infant immunization program,
      including a less expensive vaccine that preferably is delivered in a multivalent
      form.

PMID- 16806604
TI  - Virus and virus-like particle-based immunogens for Alzheimer's disease induce
      antibody responses against amyloid-beta without concomitant T cell responses.
AB  - A vaccine targeting the amyloid-beta (Abeta) peptide is a promising potential
      immunotherapy for Alzheimer's disease patients. However, experience from a recent
      clinical trial of a candidate Abeta vaccine has suggested that it is important to
      develop techniques to induce high titer antibodies against Abeta associated with
      vaccine efficacy while reducing the T cell responses against Abeta that were
      potentially responsible for serious side effects. We have previously demonstrated
      that immunization with self- and foreign antigens arrayed in a repetitive fashion
      on the surface of virus-like particles (VLPs) induces high titer antibody
      responses at low doses and in the absence of potentially inflammatory adjuvants.
      In this study, we examined the antibody and T cell responses upon immunization
      with human papillomavirus VLP- and Qbeta bacteriophage-based Abeta vaccines.
      Immunization with Abeta conjugated to VLPs or Qbeta elicited anti-Abeta antibody
      responses at low doses and without the use of adjuvants. The flexibility of these
      virus-based display systems allowed us to link and induce antibodies against
      short Abeta-derived peptides from the amino- and carboxyl-termini of the peptide.
      Immunization of mice with Abeta peptide in combination with Freund's adjuvant
      elicited predominantly IgG2c antibodies and strong T cell proliferative responses
      against Abeta. In contrast, VLP-conjugated Abeta peptides elicited more balanced
      isotype responses, dominated by IgG1. Both VLP and Qbeta-based Abeta vaccines
      induced weak or negligible T cell responses against Abeta. T cell responses were
      largely directed against linked viral epitopes. Taken together, virus-based
      vaccines that allow the presentation of Abeta in a repetitive dense array are new
      and potentially more effective vaccine candidates for Alzheimer's disease.

PMID- 16806605
TI  - Influenza A virus and the cell nucleus.
AB  - It is over 20 years since the publication of experiments that showed that
      influenza A virus RNA synthesis takes place in the cell nucleus and that here,
      the virus subverts the cellular transcription machinery to express and replicate
      its own single-strand RNA genome. In the years since, our understanding of the
      organisation of the nucleus has increased enormously, particularly with regards
      to the functional integration of the RNA polymerase II transcriptosome. This
      review summarises recent progress in defining the intimate association between
      the viral and cellular transcriptional machinery.

PMID- 16806606
TI  - Vaccination confers significant protection of sheep against infection with a
      virulent United Kingdom strain of Corynebacterium pseudotuberculosis.
AB  - Using a virulent United Kingdom Corynebacterium pseudotuberculosis isolate, an
      ovine experimental model of caseous lymphadenitis was developed, in which the
      manifestation of disease was equivalent to the naturally observed infection in
      this country. Subsequently, the capacity of several experimental vaccines to
      protect against experimental challenge was determined. Sheep were immunised with
      a recombinant derivative of phospholipase D, deriving from the virulent UK
      isolate, a formalin-killed bacterin of the same strain, or a bacterin
      supplemented with recombinant phospholipase D. Following homologous experimental
      challenge, the phospholipase D and bacterin vaccines were observed to confer
      statistically significant protection against infection, and appeared to restrict
      dissemination of challenge bacteria beyond the inoculation site in the majority
      of animals. More importantly, the combined vaccine succeeded in providing
      absolute protection against infection, whereby challenge bacteria were eradicated
      from all vaccinates. In addition to the experimental vaccines, a commercially
      available CLA vaccine, unlicensed for use in the European Union, was assessed for
      its capacity to protect against heterologous challenge. The vaccine conferred
      significant protection, although the dissemination of infection beyond the
      inoculation site was not restricted as it had been with the previous vaccines.
      However, no animals immunised with this vaccine manifested infection within the
      lungs; thus, a potentially important route of disease transmission was
      eliminated. The results of this study provide information pertinent to the
      development of an effective caseous lymphadenitis vaccination strategy in the UK.

PMID- 16806607
TI  - Real-time monitoring of the influenza vaccine field effectiveness.
AB  - Twice a year, the World Health Organization recommends the composition of the
      influenza vaccine depending on the strains which circulate several months before
      the beginning of the epidemic. Therefore, it is important to assess the field
      vaccine effectiveness (FVE) yearly. Thanks to data on vaccine coverage and data
      on influenza like illness cases collected by the French Sentinel Network, we are
      able to estimate the FVE few weeks after the beginning of the yearly influenza
      epidemic. In this paper, we have analysed the estimates obtained for the last 10
      epidemic seasons for people over and under 65. Making the assumption that the
      vaccine coverage is stable from 1 year to another, we are able to assess the
      level of the FVE few weeks after the beginning of the epidemic and we should
      detect a lack of effectiveness of the vaccine.

PMID- 16806608
TI  - The application of phosphogypsum in agriculture and the radiological impact.
AB  - Radium-226 in phosphogypsum produced in a phosphate industry, SICNG operating at
      Thessaloniki, Northern Greece since May 1966, varied from 261 to 688 Bq kg(-1)
      (mean value 508 Bq kg(-1)). This radionuclide in soil tilled with phosphogypsum
      used for agricultural purposes varied from 50 to 479 Bq kg(-1) (average 205 Bq
      kg(-1)), while in the regular soil of cultivated fields it varied from 37 to 54
      Bq kg(-1) (average 48 Bq kg(-1)). Radium-226 in rice originated from cultivated
      fields tilled with phosphogypsum or not varied from 0.36 to 1.98 Bq kg(-1)
      (average 1.53 Bq kg(-1)) with the higher values observed in samples originated
      from cultivated fields tilled with phosphogypsum. Radium-226 transfer factors,
      TF, from soil tilled with phosphogypsum to plants for the case of rice varied
      from 6.5 x 10(-3) to 2.0 x 10(-2) (geometric mean: 1.1 x 10(-2)). A mean (226)Ra
      content in rice 1.53 Bq kg(-1) results in a daily intake of (226)Ra by humans in
      Greece 0.0084 Bq day(-1) leading to an annual effective dose for adults 0.86
      microSv y(-1) which is much less in contributing to the average exposure to
      natural radiation sources (2.4 mSv y(-1)) and particularly to the part due to
      ingestion (0.29 mSv y(-1)). It is necessary to continuously control (monitoring)
      (226)Ra in phosphogypsum before any use for agricultural purposes.

PMID- 16806609
TI  - Location, identification, and size distribution of depleted uranium grains in
      reservoir sediments.
AB  - The location, nature, and size distribution of uranium-rich grains in sediment
      layers can be identified by sunbursts of etched particle tracks if each sample is
      pressed against a track detector, next irradiated with thermal neutrons, and the
      detectors then chemically etched to reveal fission tracks. The total track
      abundance from the sample is a measure of the 235U content; hence, if the bulk
      uranium (mostly 238U) has been measured, the two sets of results give the
      depletion or enrichment of the uranium. Sunbursts of tracks mark the locations of
      low-abundance, high-uranium grains allowing them to be singled out for further
      study.

PMID- 16806610
TI  - A simple and rapid method for analyzing radon in coastal and ground waters using
      a radon-in-air monitor.
AB  - We have developed a simple and portable technique for measuring moderately high
      levels of 222Rn (t1/2=3.8d) in natural waters such as coastal water, groundwater,
      and river water. The water sample is carefully collected in a glass bottle, and
      the sample bottle is connected to a radon-in-air monitor in a closed air-loop
      mode. By purging air through the sample, radon is emanated from the water until a
      chemical equilibration is obtained between the two phases. The radon in the air
      loop is determined using the radon-in-air monitor. Then, the radon in water is
      calculated by a radon-partitioning factor between water and air for a measured
      water temperature. This technique is especially convenient for determination of
      222Rn in natural waters on field sites, since it eliminates the preparation of He
      gas, cold traps, and alpha-scintillation cells and counter, which are required
      for traditional radon emanation methods.

PMID- 16806611
TI  - Distribution and inventories of fallout radionuclides (239+240Pu, 137Cs) and
      210Pb to study the filling velocity of salt marshes in Donana National Park
      (Spain).
AB  - Within an extensive multinational and multidisciplinary project carried out in
      Donana National Park (Spain) to investigate its preservation and regeneration,
      the filling velocity of the salt marshes has been evaluated through the
      calculation of their average sediment accumulation rates. (239+240)Pu and (137)Cs
      from weapons testing fallout and total (210)Pb distribution profiles and
      inventories have been determined in some of the most characteristic zones of the
      park, namely, the ponds (or "lucios") and the waterjets (or "canos"). Plutonium
      inventories range from 16 to 101 Bq m(-2), (137)Cs values fluctuate between 514
      and 3,758 Bq m(-2) and unsupported (210)Pb values comprise between 124 and 9398
      Bq m(-2). Average sedimentation rates range from 3 to 5 mm y(-1) (1952-2002).
      These data are higher than those obtained by carbon dating for the period 6,500
      AD-present, estimated as 1.5-2 mm y(-1), suggesting an increase in the
      accumulation of sediments and the alteration of the park's hydrodynamics caused
      by the re-channeling of the major rivers feeding the salt marshes.

PMID- 16806612
TI  - Concentration and characteristics of depleted uranium in biological and water
      samples collected in Bosnia and Herzegovina.
AB  - During Balkan conflicts in 1994-1995, depleted uranium (DU) ordnance was employed
      and was left in the battlefield. Health concern is related to the risk arising
      from contamination of the environment with DU penetrators and dust. In order to
      evaluate the impact of DU on the environment and population in Bosnia and
      Herzegovina, radiological survey of DU in biological and water samples were
      carried out over the period 12-24 October 2002. The uranium isotopic
      concentrations in biological samples collected in Bosnia and Herzegovina, mainly
      lichens, mosses and barks, were found to be in the range of 0.27-35.7 Bq kg(-1)
      for (238)U, 0.24-16.8 Bq kg(-1) for (234)U, and 0.02-1.11 Bq kg(-1) for (235)U,
      showing uranium levels to be higher than in the samples collected at the control
      site. Moreover, the (236)U in some of the samples was detectable. The isotopic
      ratios of (234)U/(238)U showed DU to be detectable in many biological samples at
      most sites examined, but in very low levels. The presence of DU in the biological
      samples was as a result of DU contamination in air. The uranium concentrations in
      water samples collected in Bosnia and Herzegovina were found to be in the range
      of 0.27-16.2 m Bq l(-1) for (238)U, 0.41-15.6 m Bq l(-1) for (234)U and 0.012
      0.695 m Bq l(-1) for (235)U, and two water samples were observed to be DU
      positive; these values are much lower than those in mineral water found in
      central Italy and below the WHO guideline for public drinking water. From
      radiotoxicological point of view, at this moment there is no significant
      radiological risk related to these investigated sites in terms of possible DU
      contamination of water and/or plants.

PMID- 16806613
TI  - Accidental use of the median nerve as an interposition material in first
      carpometacarpal joint arthroplasty.
AB  - Harvesting the median nerve accidentally as a tendon graft, is a major
      complication of upper extremity surgery which is noted only rarely in the
      literature. This article seems to be the first report of the median nerve being
      used as an interposition material in first carpometacarpal joint arthroplasty.

PMID- 16806614
TI  - Gender influence on fatigability of back muscles during intermittent isometric
      contractions: a study of neuromuscular activation patterns.
AB  - BACKGROUND: Gender difference in the fatigability of muscles can be attributed to
      muscle mass (or strength) and associated level of vascular occlusion, substrate
      utilization, muscle composition, and neuromuscular activation patterns. The
      purpose of this study was to assess the role of neuromuscular activation patterns
      to explain gender differences in back muscle fatigability during intermittent
      isometric tasks. METHODS: Sixteen males and 15 females performed maximal
      voluntary contractions (Strength) and a fatigue test to exhaustion (fatigue
      criterion=time to exhaustion), while standing in a static dynamometer measuring
      L5/S1 extension moment. The fatigue test consisted of repetitions of an 8-s cycle
      (1.5 s ramp to reach 40% of maximal voluntary contraction +5s plateau at 40% of
      maximal voluntary contraction +1.5s rest). Surface electromyography signals were
      collected bilaterally from 4 back muscles (multifidus at the L5 level,
      iliocostalis lumborum at L3, and longissimus at L1 and T10). FINDINGS: Males were
      stronger (P<0.05) than females (316, SD 82>196, SD 25 Nm) but showed
      significantly shorter time-to-exhaustion values (7.1, SD 5.2<13.0, SD 6.1 min.),
      the latter result being corroborated by electromyographic indices of fatigue.
      However, the gender effect on time to exhaustion disappeared when accounting for
      Strength, thus supporting the muscle mass hypothesis. Among the various
      electromyographic indices computed to assess neuromuscular activation patterns,
      the amount of alternating activity between homolateral and between contralateral
      muscles showed a gender effect (females>males). INTERPRETATION: These results
      support the muscle mass hypothesis as well as the neuromuscular activation
      hypothesis to explain gender differences in back muscle fatigability.

PMID- 16806615
TI  - The effect of necrotic lesion size and rotational degree on the stress reduction
      in transtrochanteric rotational osteotomy for femoral head osteonecrosis--a three
      dimensional finite-element simulation.
AB  - BACKGROUND: The prospect for success in the efficacy of osteotomy for precollapse
      stage of femoral head osteonecrosis depends on the ability to predict reliably
      the stress changes derived from specific osteotomies. A three-dimensional finite
      element analysis was thus designed to compute necrotic femoral head stress
      changes with different extent of necrocrosis that accompany anterior or posterior
      rotational osteotomies. METHOD: Computed tomography images of a standard
      composite femur were used to create the three-dimensional finite-element intact
      femur model. Based on the intact model, 27 models simulating three different
      levels of necrotic region together with nine different rotational osteotomies
      were created. The von Mises stress distributions of each model were analyzed and
      compared for a loading condition simulating single-legged stance. FINDINGS: (1)
      The stress reduction in anterior rotational osteotomy is more effective as
      compared to that of the posterior rotational osteotomy for various necrotic
      lesion sizes. (2) Von Mises stress on the necrotic zone decreased with increasing
      rotational angle. The decreasing rate was higher for the femoral head with a
      narrow lesion. (3) Femoral head with a wider necrotic lesion had a higher risk
      for developing collapse due to high local stress on the surface of necrotic
      region; whereas the necrotic region tended to expand in size instead of collapse
      for femoral head with a narrow lesion due to high local stress on the interface
      between necrotic region and healthy bone. INTERPRETATION: Transtrochanteric
      rotational osteotomy is a technically demanding procedure and associated with
      high complication risks, a more scrupulous planning including the finite-element
      analysis should be considered before doing surgery in clinical subjects.

PMID- 16806616
TI  - Migration and cyclic motion of a new short-stemmed hip prosthesis--a
      biomechanical in vitro study.
AB  - BACKGROUND: Uncemented, short-stemmed hip prostheses have been developed to
      reduce the risk of stress shielding and to preserve femural bone stock. The long
      term success of these implants is yet uncertain. Prerequisite for
      osseointegration is sufficient primary stability. In this study the cyclic motion
      and migration patterns of a new short-stemmed hip implant were compared with
      those for two clinically successful shaft prostheses. METHODS: The prostheses
      were implanted in paired fresh human femura and loaded dynamically (gait cycle)
      with increasing load (max 2,100 N) up to 15,000 cycles. Relative displacements
      between prosthesis and bone were recorded using a 3D-video analysis system.
      FINDINGS: The short stem displayed a biphasic migration pattern with
      stabilisation at maximum load. Initial migration was predominantly into varus and
      was greater than that for the shaft prostheses. Failure occurred in cases of poor
      bone quality and malpositioning. Cyclic motion of the short prosthesis was less
      than that for the shaft prostheses. Surface finish showed no effect. System
      stiffness for the new stem was lower than for the shaft prostheses.
      INTERPRETATION: The new stem tended to migrate initially more than the shaft
      prostheses, but stabilised when cortical contact was achieved or the cancellous
      bone was compacted sufficiently. Bone quality and correct positioning were
      important factors for the short stem. The lower cyclic motion of the new stem
      should be favourable for bony ingrowth. The lower system bending stiffness with
      the new implant indicated a more physiological loading of the bone and should
      thereby reduce the effects of stress shielding.

PMID- 16806617
TI  - Evaluation of passive and active rehabilitation and of tendon repair for partial
      tendon lacerations after three weeks of healing in canines.
AB  - BACKGROUND: Both passive and active rehabilitation have been shown to be superior
      to immobilization following partial tendon laceration, but few studies have
      directly compared these two rehabilitation protocols. In addition, controversy
      still remains over whether a partial tendon laceration should be repaired.
      METHODS: We evaluated gap formation, adhesions, gliding function and structural
      properties of repaired and unrepaired tendons following 3 weeks of unrestricted
      active rehabilitation versus passive mobilization for partial laceration of
      canine flexor digitorum profundus tendons. An ex vivo radiographic method was
      used to measure tendon excursion and rotation at each finger joint. The tendon
      was examined for adhesions, and gapping was measured with calipers. The tendons
      were tensile tested to failure. FINDINGS: We found no significant differences in
      tendon excursion, total joint rotation, or adhesions between any groups. Gap size
      was higher with active mobilization. We found no effect of rehabilitation
      protocol on the strength or stiffness of healing tendons at 3 weeks. Tendon
      repair did not affect tendon strength, but did produce higher stiffness in
      healing tendons at 3 weeks. INTERPRETATION: The results indicate that active
      rehabilitation appears safe for partial lacerations less than 60 percent. Though
      repair appears to weaken the tendon in the early stages of healing, it may
      provide some biomechanical benefit by the middle stages of healing.

PMID- 16806618
TI  - Decreased limits of stability in response to postural perturbations in subjects
      with low back pain.
AB  - BACKGROUND: Low back pain is associated with abnormal movement strategies due to
      changes in neuromuscular control. A plausible contributing factor to low back
      pain is poor control of trunk muscles, thus understanding motor control
      alterations in this population can guide rehabilitation. Quantification of
      postural responses following support surface translations is one way to examine
      motor control impairments in people with low back pain. METHODS: Twenty-four
      healthy subjects [mean 33 (SD 11) years] who had no low back pain and 26 subjects
      [mean 39 (SD 13) years] with chronic, recurrent low back pain were instructed to
      stand with feet placed on separate force plates, which were mounted on a moveable
      platform. The platform was translated unexpectedly in one of 12 directions for a
      total of 72 trials. For both the sagittal and frontal planes, the net center of
      pressure displacement was derived and the total body center of mass was
      calculated by combining kinematic and anthropometric data. FINDINGS: For sagittal
      plane responses, subjects with low back pain had reduced and delayed sagittal
      plane center of pressure responses (P<0.01) compared to the subjects without low
      back pain. In contrast, the sagittal plane center of mass responses were larger
      in magnitude (P=0.03) yet similarly delayed in onset (P=0.04) for the low back
      pain group. Frontal plane responses did not differ between groups.
      INTERPRETATION: Subjects with low back pain have altered automatic postural
      coordination, both in terms of magnitude and timing of responses, indicating
      alterations in neuromuscular control.

PMID- 16806619
TI  - Evaluation of hydrophobicity in PAH-contaminated soils during phytoremediation.
AB  - The impact of recalcitrant organic compounds on soil hydrophobicity was evaluated
      in contaminated soil from a manufactured gas plant site following 12 months of
      phytoremediation. Significant reduction in soil wetting and water retention was
      observed in contaminated soil compared to an uncontaminated control.
      Phytoremediation was effective at reducing total PAHs by 69% with corresponding
      changes in soil classification from extremely hydrophobic (initial sample) to
      moderately-strongly hydrophobic (planted) and hydrophilic-very hydrophilic
      (unplanted) after 12 months. The greatest reduction in soil hydrophobicity was
      observed in the unplanted, unfertilized treatments that had the lowest removal
      rate of PAHs. The presence of plants may contribute to hydrophobicity in
      contaminated soil.

PMID- 16806620
TI  - Chlorobiphenyls in sediments.

PMID- 16806621
TI  - Cognitive vulnerability: a model of the etiology of fear.
AB  - This paper attempts to fill the partial theoretical vacuum surrounding the
      understanding of fear acquisition. A review of recent and contemporary theories
      of the etiology of fear is presented, serving as a justification for further
      theorizing and allowing for greater understanding of those aspects of fear that
      remain to be adequately explained. A new model of the etiology of specific fears
      is subsequently put forward and the various aspects and implications of this
      model are discussed. How an individual perceives a stimulus is proposed as being
      critical in determining fear in relation to the stimulus. In particular,
      perceptions of the stimulus as uncontrollable, unpredictable, dangerous and
      disgusting create a schema of vulnerability. The Cognitive Vulnerability Model
      integrates much of the extensive body of research on fears and specific phobias
      into a unifying theory of the etiology of fear. The model offers parsimonious
      explanations for the various characteristics of specific fears and phobias.

PMID- 16806622
TI  - The permeable institution: an ethnographic study of three acute psychiatric wards
      in London.
AB  - In Asylums, Goffman [1961. Asylums. London: Penguin] identified some permeable
      features of the old mental hospitals but presented them as exceptions to the rule
      and focused on their impermeable aspects. We argue that this emphasis is no
      longer valid and offer an alternative ideal type that better represents the
      reality of everyday life in contemporary 'bricks and mortar' psychiatric
      institutions. We call this the "permeable institution". The research involved
      participant observation of between 3 and 4 months and interviews with patients,
      patient advocates and staff on 3 psychiatric wards. Evidence for permeability
      includes that ward membership is temporary and changes rapidly (patients tend to
      have very short stays and staff turnover is high); patients maintain contact with
      the outside world during their stay; and institutional identities are blurred to
      the point where visitors or new patients can easily mistake staff and patients
      for one another. Permeability has both positive consequences (e.g., reduced risk
      of institutionalism), and negative consequences (e.g., unwanted people coming
      into hospital to cause trouble, and illicit drug use among patients). Staff
      employ various methods to regulate their ward's permeability, within certain
      parameters. The metaphor of the total/closed institution remains valuable, but it
      fails to capture the highly permeable nature of the psychiatric institutions we
      studied. Analysts may therefore find the permeable institution a more helpful
      reference point or ideal type against which to examine and compare empirical
      cases. Perhaps most helpful is to conceptualise a continuum of institutional
      permeability with total and permeable institutions at each extreme.

PMID- 16806623
TI  - On feeling in control: a biological theory for individual differences in control
      perception.
AB  - This review aims to create a cross-disciplinary framework for understanding the
      perception of control. Although, the personality trait locus of control, the most
      common measure of control perception, has traditionally been regarded as a
      product of social learning, it may have biological antecedents as well. It is
      suggested that control perception follows from the brain's capacity for self
      regulation, leading to flexible and goal directed behaviours. To this account, a
      model is presented which spans several levels of analyses. On a behavioural
      level, control perception may be a corollary of emotion regulation, executive
      functions, and social cognition. On a neural level, these self-regulatory
      functions are substantiated in part by the dorsolateral and ventral prefrontal
      cortex and the anterior cingulate cortex. In addition, a possible role of
      subcortical-cortical dopamine pathways underlying control perception is
      discussed.

PMID- 16806624
TI  - Cerebellar syndrome in a patient with pneumonia under lithium treatment: A case
      report.
AB  - We report the case of a 31-year-old man with bipolar disorder who was on a
      combination therapy of lithium, lamotrigine and escitalopram. Serum lithium level
      was within therapeutic range. Cerebellar symptoms such as dysarthria, ataxia, and
      dyskinesia developed in the patient following the pneumonia. Cerebellar syndrome
      was most likely due to lithium neurotoxicity, which was associated with
      additional factors such as acute febrile pneumonia, fever and hyponatremia. The
      reported case suggests that infections may increase the risk of cerebellar
      toxicity of lithium, even in the therapeutic doses.

PMID- 16806625
TI  - Serum creatine kinase levels in chronic psychosis patients--a comparison between
      atypical and conventional antipsychotics.
AB  - Creatine kinase is an important enzyme in the energy metabolism of many cell
      types, including muscle cells. Increased serum levels of creatine kinase may
      serve as a marker of enhanced creatine kinase synthesis in muscle cells or muscle
      cell membrane damage. The purpose of this study was to compare serum creatine
      kinase levels in chronic psychosis patients treated with either atypical or
      conventional antipsychotics. Forty-nine patients, receiving clozapine (n=18), or
      olanzapine (n=18), or conventional agents (n=13), were studied. Fasting serum
      samples were analyzed for creatine kinase. A significant difference in median
      creatine kinase level was found among the treatment groups (p=0.03), in that the
      creatine kinase level was higher both in the patients receiving clozapine and in
      the patients receiving olanzapine, compared to that in patients receiving
      conventional antipsychotics, p=0.001 and p<0.0001, respectively. In addition,
      elevated creatine kinase levels above the upper limit of normal were found in 6
      (17%) of the patients treated with clozapine or olanzapine, but in none of the
      patients treated with conventional agents. In summary, the present results
      indicate that therapy with atypical antipsychotics like clozapine and olanzapine,
      in contrast to conventional agents, may be associated with serum creatine kinase
      elevation.

PMID- 16806626
TI  - Effects of clozapine, olanzapine and haloperidol on nitric oxide production by
      lipopolysaccharide-activated N9 cells.
AB  - Schizophrenia is a devastating illness of unknown etiology and the basis for its
      treatment rests in the symptomatic response to antipsychotics. It was found that
      some of the patients with schizophrenia elicited microglia activation. The
      present study used lipopolysaccharide (LPS)-activated mouse microglial cell line
      N9 as an in vitro model to mimic microglia activation seen in the patients with
      schizophrenia. The effects of clozapine, olanzapine and haloperidol on the
      release of nitric oxide (NO) by LPS-stimulated N9 cells were investigated. The
      results showed that olanzapine significantly inhibited NO release by LPS
      stimulated N9 cells. Clozapine and haloperidol did not show significant effects
      on this model. The present study suggested that the inhibiting effect of
      olanzapine on the NO release by LPS-stimulated microglial cells might be a new
      mechanism through which olanzapine exhibits its therapeutic effect in the
      treatment of schizophrenia.

PMID- 16806627
TI  - Estimation of ochratoxin A in portuguese population: new data on the occurrence
      in human urine by high performance liquid chromatography with fluorescence
      detection.
AB  - With increasing knowledge of the persistence of OTA in the food chain, exposure
      to this mycotoxin is a potential human health hazard to humans, and evaluating
      its presence in populations has become highly important. A sensitive and accurate
      analytical method for the determination of ochratoxin A in urine was validated,
      since is less invasive than blood monitoring. It involves extraction with 5%
      NaHCO3, immunoaffinity column (IAC) for clean-up and high performance liquid
      chromatography with fluorescence detection (HPLC-FD). The limit of quantification
      was 0.02 ng/mL of urine (1.3 ng/mL of the extract injected) and recovery of
      ochratoxin A from urine samples spiked at the three fortification levels, were
      higher than 90% with RSD lower than 9%. The identification of OTA was confirmed
      by methyl ester derivatization and then HPLC analysis. Based in ours first
      results we can assume that OTA conjugation with glucuronic acid in human urine
      occurs. In the present study, we follow up OTA levels in 60 urine samples of
      inhabitants from Coimbra city, Portugal, in order to evaluate population
      contamination, and the presence of OTA was found in 42 samples, at concentrations
      above the LOQ, ranged between 0.021 and 0.105 ng/mL.

PMID- 16806628
TI  - Protocatechuic acid suppresses MPP+ -induced mitochondrial dysfunction and
      apoptotic cell death in PC12 cells.
AB  - Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of
      Alpinia (A.) oxyphylla, showed antioxidant neuroprotective effect in our previous
      study. Here, we investigated the effect of PCA on the MPP(+)-induced
      mitochondrial dysfunction and apoptotic cell death in PC12 cells. The apoptosis
      in MPP(+)-induced PC12 cells was associated with loss of mitochondrial membrane
      potential, the formation of reactive oxygen species (ROS), GSH depletion,
      activation of caspase-3 and down-regulation of Bcl-2. In contrast, treatment of
      PC12 cells with PCA significantly prevented the above-mentioned mitochondrial
      dysfunction. Our data pointed to the potential clinical application/use of PCA to
      overcome neurodegenerative diseases such as Parkinson's disease.

PMID- 16806629
TI  - Cyclic fatty acid monomer formation in domestic frying of frozen foods in
      sunflower oil and high oleic acid sunflower oil without oil replenishment.
AB  - During the frying process, oxidation, hydrolysis, polymerization, isomerization,
      and cyclization occur. Polymers and Cyclic fatty acid monomers (CFAM) are
      potentially toxic, and the latter are detected at relatively low levels (0.01
      0.7%) in used frying oils. Twenty fryings of different frozen foods were carried
      out over 10 consecutive days in sunflower oil (SO) and in high oleic acid
      sunflower oil (HOSO). Fatty acid methyl ester derivates were hydrogenated with
      platinum oxide catalyst under hydrogen. Ethyl palmitate was added as an internal
      standard before hydrogenation. The CFAM obtained were isolated, concentrated and
      quantified by HPLC using a reverse-phase column followed by gas chromatography.
      Linear adjustments between total and individual CFAM content and the number of
      frying operations performed with both oils were established by analysis of
      variance. The comparison between linear equation adjustments of both oils was
      performed by a two-way analysis of covariance. After 20 fryings 15.4 +/- 0.06 g
      polar content/100 g oil, 7.15 +/- 0.08 g polymers/ oil, 11.52 +/- 0.08 g
      polymers/100g oil and 855 +/- 8.9 mg CFAM/kg oil were detected in SO. A 10 mg/100
      mg oil of altered fatty acid content correspond to 700 mg/kg CFAM, while 25%
      polar material and 10% polymer content would correspond to about 850-1,000 mg
      CFAM/kg oil. Data suggest that frying with SO produces in each new frying 9 mg
      CFAM/kg more than frying with HOSO (p < 0.001). After frying cyclopentyl
      structures were more than twice as abundant as cyclohexyl fatty acids in both
      oils. Bicyclic compound formation was significantly higher in SO (p < 0.001).
      Because digestion and absorption of polar material, polymers and CFAM occur, data
      clearly show the advantageousness and advisability of frying with HOSO rather
      than SO.

PMID- 16806630
TI  - [Abbe-Mustarde's flap with lower lid transposition: three clinical cases].
AB  - The ideal solution first recommended is the use of Abbe-Mustarde's flap with
      lower lid transposition to rebuild the total loss of the upper eyelid. Every step
      of the surgical technique has been detailed to improve the result and keep the
      drawbacks under control. After having read articles on this subject, we describe
      three clinical cases, which enable us to compare with others surgical techniques
      that cannot rebuild all the levels of the eyelids and the edge of the eyelashes.

PMID- 16806631
TI  - A dose-response study following in utero and lactational exposure to di-(2
      ethylhexyl) phthalate (DEHP): effects on androgenic status, developmental
      landmarks and testicular histology in male offspring rats.
AB  - An extensive dose-response study following in utero and lactational exposure to
      di-(2-ethylhexyl) phthalate (DEHP) was conducted. A wide range of low and high
      DEHP doses were tested. Reproductive effects were evaluated on male offspring
      rats. Female Wistar rats were treated daily with DEHP and peanut oil by gavage
      from gestation day 6 to lactation day 21 at doses of 0.015, 0.045, 0.135, 0.405
      and 1.215 mg DEHP/kg body weight (bw)/day (low doses) and at 5, 15, 45, 135 and
      405 mg DEHP/kg bw/day (high doses). Nipple retention and reduced anogenital
      distance, both sensitive markers of anti-androgenic effects during development,
      were only seen in males exposed to the highest dose (405 mg/kg/day). Delayed
      preputial separation was observed in animals exposed to 15 mg DEHP/kg/day and
      higher doses. Histopathological examination of the testis on postnatal days
      (PNDs) 1 and 22 revealed changes at 135 and 405 mg DEHP/kg/day. The most
      prominent finding on PND 1 was the presence of bi- and multinucleated gonocytes.
      On PND 22 signs of reduced germ cell differentiation in seminiferous tubules of
      exposed animals were observed. Testis weight on PND 22 was significantly
      increased at 5, 15, 45 and 135 mg/kg/day, an effect that qualitatively differs
      from exposure to higher doses. The current results show that DEHP acts as an anti
      androgen at a high dose exposure (405 mg/kg/day). However, these results also
      indicate that other subtle developmental effects occur at lower DEHP doses.

PMID- 16806632
TI  - Comparative study of natural antioxidants - curcumin, resveratrol and melatonin -
      in cadmium-induced oxidative damage in mice.
AB  - The present study was designed to examine the antioxidative effect of curcumin,
      resveratrol and melatonin pre-treatment on cadmium-induced oxidative damage and
      cadmium distribution in an experimental model in mice. Male CD mice were treated
      once daily for 3 days with curcumin (50mg/kg b.w., p.o.), resveratrol (20mg/kg
      b.w., p.o.) or melatonin (12mg/kg, p.o.), dispersed in 0.5% methylcellulose. One
      hour after the last dose of antioxidants cadmium chloride was administered
      (7mg/kg b.w., s.c.) to pre-treated animals and control animals receiving
      methylcellulose. At 24th h after Cd administration the lipid peroxidation (LP -
      expressed as malondialdehyde production), reduced glutathione (GSH), catalase
      (CAT) and glutathione peroxidase (GPx) were estimated in liver homogenates.
      Cadmium concentration was measured in the liver, kidneys, testes and brain by
      AAS. Cadmium chloride administration to mice induced hepatic lipid peroxidation
      (to 133%, p<0.001), decreased GSH content (to 65%, p<0.001) and inhibited
      catalase (to 68%, p<0.001) and GPx activity (to 60%, p<0.001) in the liver.
      Curcumin, resveratrol and melatonin oral pre-treatment completely prevented the
      Cd-induced lipid peroxidation and Cd-induced inhibition of GPx hepatic activity.
      Resveratrol was effective against Cd-induced inhibition of catalase activity
      (p<0.001). The decrease in hepatic GSH level was not prevented by curcumin,
      resveratrol or melatonin pre-treatment. In mice treated with antioxidants alone
      the level of LP, GSH, GPx or CAT was not different from control levels. The pre
      treatment with antioxidants did not affect cadmium distribution in the tissues of
      Cd-intoxicated mice. The results demonstrate that curcumin, resveratrol and
      melatonin pre-treatment effectively protect against cadmium-induced lipid
      peroxidation and ameliorate the adverse effect of cadmium on antioxidant status
      without any reduction in tissue Cd burden.

PMID- 16806633
TI  - Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats.
AB  - Twenty years after Chernobyl disaster, many people are still chronically exposed
      to low dose of (137)Cs, mainly through the food consumption. A large variety of
      diseases have been described in highly exposed people with (137)Cs, which include
      bone disorders. The aim of this work was to investigate the biological effects of
      a chronic exposure to (137)Cs on Vitamin D(3) metabolism, a hormone essential in
      bone homeostasis. Rats were exposed to (137)Cs in their drinking water for 3
      months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar
      concentration ingested by the population living in contaminated territories in
      the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D(3)
      metabolism, related nuclear receptors and Vitamin D(3) target genes were assessed
      by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and
      phosphate levels were measured in plasma. An increase in the expression level of
      cyp2r1 (40%, p<0.05) was observed in the liver of (137)Cs-exposed rats. However a
      significant decrease of Vitamin D (1,25(OH)D(3)) plasma level (53%, p=0.02) was
      observed. In brain, cyp2r1 mRNA level was decreased by 20% (p<0.05), while the
      expression level of cyp27b1 is increased (35%, p<0.05) after (137)Cs
      contamination. In conclusion, this study showed for the first time that chronic
      exposure with post-accidental doses of (137)Cs affects Vitamin D(3) active form
      level and induces molecular modifications of CYPs enzymes involved its metabolism
      in liver and brain, without leading to mineral homeostasis disorders.

PMID- 16806634
TI  - Crystal structure of the bacterial ribosomal decoding site complexed with
      amikacin containing the gamma-amino-alpha-hydroxybutyryl (haba) group.
AB  - Amikacin is the 4,6-linked aminoglycoside modified at position N1 of the 2
      deoxystreptamine ring (ring II) by the L-haba group. In the present study, the
      crystal structure of a complex between oligonucleotide containing the bacterial
      ribosomal A site and amikacin has been solved at 2.7 A resolution. Amikacin
      specifically binds to the A site in practically the same way as its parent
      compound kanamycin. In addition, the L-haba group interacts with the upper side
      of the A site through two direct contacts, O2*...H-N4(C1496) and N4*
      H...O6(G1497). The present crystal structure shows how the introduction of the L
      haba group on ring II of aminoglycoside is an effective mutation for obtaining a
      higher affinity to the bacterial A site.

PMID- 16806635
TI  - Metal(loid)s and radionuclides cytotoxicity in Saccharomyces cerevisiae. Role of
      YCF1, glutathione and effect of buthionine sulfoximine.
AB  - The presence of heavy metal(loid)s in soils and waters is an important issue with
      regards to human health. Taking into account speciation problems, in the first
      part of this report, we investigated under identical growth conditions, yeast
      tolerance to a set of 15 cytotoxic metal(loid)s and radionuclides. The yeast
      cadmium factor 1 (YCF1) is an ATP-Binding Cassette transporter mediating the
      glutathione detoxification of heavy metals. In the second part, metal(loid)s that
      could be handled by YCF1 and a possible re-localisation of the transporter after
      heavy metal exposure were evaluated. YCF1 and a C-terminal GFP fusion, YCF1-GFP,
      were overexpressed in wild-type and Deltaycf1 strains. Both forms were
      functional, conferring a tolerance to Cd, Sb, As, Pb, Hg but not to Ni, Zn, Cu,
      Ag, Se, Te, Cr, Sr, Tc, U. Confocal experiments demonstrated that during exposure
      to cytotoxic metals, the localisation of YCF1-GFP was restricted to the yeast
      vacuolar membrane. In the last part, the role of glutathione in this resistance
      mechanism to metal(loid)s was studied. In the presence of heavy metals,
      application of buthionine sulfoximine (BSO), a well-known inhibitor of gamma
      glutamylcysteine synthetase, led to a decrease in the cytosolic pool of GSH and
      to a limitation of yeast growth. Surprisingly, BSO was able to phenocopy the
      deletion of gamma-glutamylcysteine synthetase after exposure to Cd but not to Sb
      or As. In the genetic context of gsh1 and gsh2 yeast mutants, the critical role
      of GSH for Cd, As, Sb and Hg tolerance was compared to that of wild-type and
      Deltaycf1.

PMID- 16806636
TI  - Time to give the first medication during resuscitation in out-of-hospital cardiac
      arrest.
AB  - OBJECTIVE: There is no evidence showing an impact from any advanced cardiac life
      support (ACLS) medications on patient survival following cardiac arrest. One
      potential reason for a lack of such benefit may be medication timing. We formed
      the hypothesis that medications are given late after rescuer arrival, limiting
      any benefit. We performed a meta-analysis to determine the time from emergency
      medical services (EMS) dispatch to first medication administration, regardless of
      route, during out-of-hospital cardiac arrest (OOHCA). Then, the mean time and
      ranges of reported study medication delivery in clinical trials where medication
      was the experimental intervention was determined. METHODS: We conducted a
      comprehensive literature review between January 1990 and August 2005 in MEDLINE
      using the following MeSH headings: cardiopulmonary resuscitation, cardiac arrest,
      heart arrest, EMS, EMT, ambulance, and the names of all ACLS medications. We
      reviewed the abstracts of 632 studies and full manuscripts of 248 published
      papers. We eliminated the following articles from further analysis: non-peer
      reviewed; all without human primary data (includes review articles, guidelines or
      consensus manuscripts, editorials, or simulation studies); animal data; case
      reports. We used no language restriction. From this search, our independent
      reviewers found 17 papers that contained information on time to medication
      administration. RESULTS: We analyzed reporting of drug delivery time to 7617
      patients in 32 different emergency medical services systems. Time to first
      medication delivery by any route was a mean of 17.7 min (range 10.0-25.0; 95% CI
      around mean 10.6, 24.8). Time to intravenous experimental medication
      administration was a mean of 19.4 min (range 13.3-25.0; 95% CI around mean 12.8,
      25.9). CONCLUSIONS: Medications are given late during out-of-hospital cardiac
      arrest, even in cohorts where drug delivery is a key study intervention.

PMID- 16806637
TI  - Inter-rater reliability for witnessed collapse and presence of bystander CPR.
AB  - OBJECTIVE: Witnessed collapse and bystander CPR are the variables most frequently
      associated with good outcome from out-of-hospital cardiac arrest (OOHCA). The
      reliability of abstracting witnessed collapse and bystander CPR from prehospital
      Emergency Medical Services (EMS) patient care records (PCRs) is not known. We
      sought to determine the inter-rater reliability for different methods of
      ascertaining and defining witnessed collapse and performance of bystander CPR.
      METHODS: A sample of 100 PCRs for patients with OOHCA was selected at random from
      a pool of 325 PCRs between May 2003 and January 2005. Paramedics used a drop down
      menu to indicate witnessed collapse and bystander CPR, and completed a narrative
      description of the event. An on-scene EMS physician also completed a data sheet.
      The PCR was examined by two separate evaluators to determine the presence of
      witnessed collapse and bystander CPR. A consensus was reached by three other
      reviewers using all available data sources. Inter-rater agreement was quantified
      using the unweighted kappa statistic. RESULTS: For witnessed collapse, there is
      substantial agreement between the following: individual evaluators (kappa=0.76,
      S.D.=0.07), individual evaluators and consensus group (kappa=0.61, S.D.=0.07 and
      0.66, S.D.=0.07), and physician and consensus group (kappa=0.68, S.D.=0.08).
      Agreement between individual evaluators and the physician was fair to moderate
      (kappa=0.38, S.D.=0.07 and 0.44, S.D.=0.07). Agreement between individual
      evaluators, physician, consensus group and the PCR drop down menu was fair to
      moderate (kappa range 0.33, S.D.=0.09 to 0.54, S.D.=0.09). For bystander CPR,
      there is substantial agreement between the individual evaluators and the
      consensus group (kappa=0.64, S.D.=0.07 and 0.63, S.D.=0.06) and between the
      physician and the consensus group (kappa=0.61, S.D.=0.08). Agreement between the
      two individual evaluators is moderate (kappa=0.59, S.D.=0.07). Agreement between
      the physician and individual evaluators is fair (kappa=0.36, S.D.=0.07 and 0.38,
      S.D.=0.07). The PCR drop down menu had moderate to substantial agreement with the
      individual evaluators, physician, and consensus group (kappa range 0.50,
      S.D.=0.09 to 0.75, S.D.=0.09). CONCLUSIONS: Determination of witnessed collapse
      and bystander CPR during OOHCA may be less reliable than previously thought, and
      differences between methods of rating could influence study results.

PMID- 16806638
TI  - Moderate sea states do not influence the application of an AED in rigid
      inflatable boats.
AB  - PURPOSE: This study was to determine if the AED can be operated correctly on
      board rigid inflatable rescue boats (RIBs), and if downloading of data later for
      quality control is possible. METHODS: Six AEDs were tested for their reliability,
      robustness and stability. Data were collected on three different types of RIBs,
      in a harbour and at sea. Each AED was connected to a volunteer and a manikin
      simulating VF. Data from the AED were continuously collected. RESULTS: At one of
      the RIBs each AED became wet; no AED had a technical problem. When connected to
      the volunteer, the ECGs delivered by the AEDs showed a regular sinus rhythm. When
      connected to a manikin in VF, each AED was able to recognise VF and to provide a
      shock. There were differences in the time between first analysis and the shock.
      The voice prompt of the Zoll AED Plus was 'understandable', while the other AEDs
      were 'difficult to understand'. We had a problem with the infrared connection,
      which means that evaluation and quality control afterwards may be difficult.
      CONCLUSION: The use of AEDs on RIBs during patient transport over calm water is
      possible and effective. The AED should have a screen and better features to
      download data. However, AEDs are only worthwhile when they fit well in the Chain
      of Survival (fast arrival, immediately availability of an AED, trained provider
      and advanced life support).

PMID- 16806639
TI  - Influence of medical direction on the management of prehospital myocardial
      infarction.
AB  - Prehospital management of myocardial infarction was evaluated in two differently
      structured Emergency Medical Service (EMS) systems in Southern Finland: a
      physician directed EMS with on-site physician involvement (physician EMS) and an
      EMS without operational physician involvement with paramedics only (non-physician
      EMS). The management of 641 consecutive acute ST-elevation myocardial infarction
      (STEMI) patients between 1997 and 1999 (263 patients in the physician EMS group
      and 378 patients in non-physician EMS group) were studied. Patients treated in
      the physician EMS received all necessary medical care including thrombolytic
      therapy at the scene whereas patients in the non-physician EMS were transported
      to hospital for definitive treatment after initial care. There were no
      differences in the demographics of the patients. The delays from onset of pain to
      initiation of thrombolysis were shorter in the physician EMS-group (124+/-101 min
      (25-723) versus 196+/-150 min (12-835), p<0.001). In 2% of the patients in the
      physician EMS group the pain to therapy-time was unknown compared to 27% in the
      non-physician EMS group (p<0.001). Fifty-two patients (20%) in the physician EMS
      received thrombolytic therapy after cardiopulmonary resuscitation compared to two
      patients in the non-physician EMS (p<0.001). Of the resuscitated patients in the
      physician directed EMS group 60% were discharged from the hospital, and 44% of
      these had a good neurological recovery. We conclude that a physician directed EMS
      is able to reduce the pain to therapy delays significantly in STEMI patients and
      may offer thrombolytic therapy to a wider patient group compared to an EMS
      without operational medical involvement.

PMID- 16806640
TI  - A moderate dose of propofol and rapidly induced mild hypothermia with
      extracorporeal lung and heart assist (ECLHA) improve the neurological outcome
      after prolonged cardiac arrest in dogs.
AB  - BACKGROUND AND PURPOSE: Propofol has been shown to protect against neuronal
      damage induced by brain ischaemia in small animal models. We reported previously
      that mild hypothermia (33 degrees C) in combination with extracorporeal lung and
      heart assist (ECLHA) improved the neurological outcome in dogs with cardiac
      arrest (CA) of 15 min induced during normothermia. In the present study, we
      investigated the neuroprotective effect of propofol infusion under mild
      hypothermia with ECLHA in this model. METHODS: Twenty-one female dogs (15 mongrel
      dogs and 6 beagles) were divided into three groups: Midazolam 0.1 mg/(kg h)
      infusion group (M, n=7), Propofol 2 mg/(kg h) infusion group (P2, n=7), Propofol
      4 mg/(kg h) infusion group (P4, n=7). Normothermic ventricular fibrillation (VF)
      was induced in all dogs for 15 min, followed by brief ECLHA and 168 h of
      intensive care. The drug infusion was initiated at a constant rate after the
      restoration of spontaneous circulation (ROSC) to 24 h. Mild hypothermia (33
      degrees C) was maintained for 20 h. Neurological deficit scores (NDS: 0%=normal,
      100%=brain death) were evaluated for neurological function from 33 to 168 h.
      RESULTS: One dog in the M group died, and the remaining dogs survived for 168 h.
      The P4 group showed better neurological recovery compared with the M group (48 h,
      21+/-16% versus 32+/-15%; 72 h, 7+/-6% versus 25+/-11%; 96 h, 6+/-6% versus 21+/
      6%; 120 h, 5+/-5% versus 20+/-6%; 144 h, 4+/-4% versus 20+/-6%; 168 h, 4+/-4%
      versus 20+/-6%, p<0.05). One dog in the P2 and three dogs in the P4 group
      achieved full neurological recovery (NDS: 0%). The number of intact pyramidal
      cells in the hippocampal CA1 was greater in the propofol groups than midazolam
      group (p<0.05). CONCLUSION: The combination of propofol infusion at a rate of 4
      mg/(kg h), 24h and rapidly induced mild hypothermia (33 degrees C) with ECLHA
      might provide a successful means of cerebral resuscitation from CA.

PMID- 16806641
TI  - Calculating early warning scores--a classroom comparison of pen and paper and
      hand-held computer methods.
AB  - To assist in the early detection of critical illness, many hospitals now use a
      "track and trigger" system that allocates points to routine vital signs
      measurements on the basis of their derangement from an arbitrarily agreed
      "normal" range. These points are summed to provide an early warning score (EWS).
      Little is known about the accuracy with which EWS are calculated and charted. We
      compared the speed and accuracy of charting the weighted value attributed to each
      vital sign, and of calculating the EWS, using the traditional pen and paper
      method with that using a specially programmed, personal digital assistant
      (VitalPAC). Incorrect entries or omissions occurred in 24 (29%) of 84 EWS
      computed using pen/paper compared to 8 (10%) computed using the VitalPAC method.
      Fewer incorrect clinical actions were indicated using EWS derived via the
      VitalPAC method (4/84, 5%) than from those calculated using pen/paper (12/84,
      14%). The mean time (+/-S.D.) taken for participants to calculate and chart a set
      of weighted values and EWS using the pen/paper method was 67.6+/-35.3 s (n=84).
      The corresponding time taken to enter a set of physiological data using the
      VitalPAC was 43.0+/-23.5 s (n=84). By comparison with the conventional pen/paper
      method, the use of VitalPAC was on average 1.6-times faster. The use of a device
      such as VitalPAC offers significant advantages both in speed and accuracy of
      recording of EWS.

PMID- 16806642
TI  - Emergency medical service providers' experience with family presence during
      cardiopulmonary resuscitation.
AB  - OBJECTIVE: To describe emergency medical service providers' experiences with
      family member presence during resuscitation, and to determine whether those
      experiences are similar within urban and suburban settings. METHODS: We conducted
      a personally distributed survey of a convenience sample of urban and suburban
      emergency medical service (EMS) providers presenting to two Midwestern Emergency
      Departments. Providers were questioned as to their experiences with resuscitating
      patients in the presence of family members. RESULTS: There were 128 respondents
      to the survey (59 urban and 69 suburban), of which 70.1% were EMT-Paramedics. No
      provider who was approached refused participation. Nearly all (122) had performed
      CPR in the presence of family members, with most (77%) performing greater than
      20. Subjects averaged 12.3 years of experience. The majority of urban and
      suburban providers felt it was inappropriate for family to witness resuscitations
      (75.9% versus 60.3%, respectively; p=0.068). Many providers reported feeling
      uncomfortable with family presence (31.5% urban versus 44.8% suburban; p=0.136),
      and few preferred that family witness the resuscitation (13.2% urban versus 15.4
      suburban; p=0.738). A minority of providers believed that family were better
      prepared to accept the death of the patient (37.0% urban versus 37.6% suburban;
      p=0.939). Approximately half felt comfortable providing emotional support (66.0%
      urban versus 53.7% suburban; p=0.173). Many felt that family caused a negative
      impact during resuscitation (53.7% urban and 36.8% suburban; p=0.061). Urban
      providers more often reported feeling threatened by family members during
      resuscitation (66.7% versus 39.7%; p=0.003), and felt that family often
      interfered with their ability to perform resuscitations (35.6% versus 16.4%,
      p=0.014). CONCLUSIONS: EMS providers have substantial experience with family
      witnessed resuscitations, are uncomfortable about their presence, and often must
      provide support for families. While urban providers tended to report more
      negative experiences and perceptions, there were minimal differences between the
      two groups.

PMID- 16806643
TI  - Thyrotoxic heart disease.
AB  - Patients with tachyarrythmias as a result of thyroid storm have been typically
      treated with beta-blockers to decrease the heart rate and alleviate beta-receptor
      mediated symptoms such as anxiety and tremulousness. We report an unusual case of
      a previously well young man presenting to the emergency department with atrial
      flutter and who was clinically hyperthyroid. The patient was treated with
      propanolol to control his heart rate but suffered cardiovascular collapse.
      Although the patient was successfully resuscitated, he required inotropic support
      and intra-aortic balloon pump. The use of propanolol should be carefully
      considered in patients with thyrotoxic cardiomyopathy especially in those with
      heart failure because of the risk of exacerbation.

PMID- 16806644
TI  - Reduced survival following resuscitation in patients with documented clinically
      abnormal observations prior to in-hospital cardiac arrest.
AB  - BACKGROUND: Patients suffering in-hospital cardiac arrest (IHCA) often have
      abnormal clinical observations documented prior to the arrest. This study
      assesses whether these patients have a less favourable outcome following IHCA.
      METHODS: A multiple logistic regression analysis of retrospectively collected
      hospital chart data and prospectively collected Utstein style resuscitation data.
      Patients were defined as having abnormal clinical observations if they had one of
      the following documented 8 h before the arrest: systolic arterial blood pressure
      below 90 or over 200, pulse rate below 40 or over 140 beats per min or oxygen
      saturation below 90% with or without supplemental oxygen. Pre-arrest variables
      included were: age, sex and functional status, co-morbidities, reason for
      hospital admission, days in the hospital before the arrest, witnessed or un
      witnessed arrest, arrest occurring outside regular working hours, monitored or
      non-monitored ward, whether basic life support was performed before the arrival
      of the resuscitation team, delay to arrival of resuscitation team and initial
      rhythm. RESULTS: Survival to hospital discharge of patients with clinically
      abnormal observations was 9% and among those without 18% (p=0.037). Independent
      pre-arrest predictors of survival were: un-witnessed arrest (odds ratio [OR] 0.1,
      confidence interval (CI) 0.01-0.8), initial rhythm other than ventricular
      fibrillation or ventricular tachycardia (OR 0.13, CI 0.05-0.3), delay to arrival
      of the resuscitation team exceeding 2 min (median) (OR 0.4, CI 0.15-0.9) and the
      presence of documented clinical abnormal observations prior to the arrest (OR
      0.3, CI 0.09-0.95). CONCLUSIONS: Patients with documented clinically abnormal
      observations before IHCA have a worse outcome than those without, despite prompt
      resuscitation. Efforts should be made to identify these patients in time, thereby
      possibly avoiding the arrest. This can also be used when assessing the prognosis
      in IHCA.

PMID- 16806645
TI  - Uterocutaneous fistula in term abdominal pregnancy.

PMID- 16806646
TI  - Successful use of insulin glargine during entire pregnancy until delivery in six
      Type 1 diabetic women.

PMID- 16806647
TI  - Follow-up of screening patients conservatively treated for cervical
      intraepithelial neoplasia grade 2-3.
AB  - OBJECTIVES: To evaluate the frequency and correlates of non-adherence to follow
      up among patients conservatively treated for CIN2-3. STUDY DESIGN: Study
      population comprised 1560 patients aged 25-64 years from a screening programme in
      northern Italy. The regional standard protocol was used as a reference.
      Multinomial logistic regression analysis was used to estimate the odds ratio
      probability of a patient being lost to follow-up (no check-ups within 27 months
      of treatment) or incompletely followed-up (1-3 negative check-ups) versus having
      4 negative check-ups. RESULTS: Three hundred twenty-six patients (21%) were lost
      to follow-up, 678 (43%) were incompletely followed-up, 352 (23%) presented for 4
      negative check-ups and 204 (13%) were diagnosed with persistent disease. The
      probability of no or incomplete follow-up was greater for patients who lived in
      the urban district, who were treated in private settings (versus screening
      centres), who exhibited a visibile squamocolumnar junction on pre-treatment
      colposcopy, who were treated with cold knife excision and local destructive
      therapy (versus loop diathermy excision), and whose surgical specimens had
      positive excision margins. CONCLUSIONS: Adherence to the reference protocol was
      poor. Factors involved in follow-up failures require greater clinical attention.

PMID- 16806648
TI  - The proteolytic profile of prelabour ruptured amnion at term: a case-control
      study.
AB  - OBJECTIVES: The aim of this study was to investigate whether prelabour ruptured
      membranes at term display increased proteolytic activity and to determine whether
      regional structural alterations within membranes are reflective of regional
      variations in proteolytic activity. STUDY DESIGN: Multiple amnion samples were
      collected from 37 women with prelabour membrane rupture and 37 women whose
      membranes ruptured spontaneously during labour. In all cases the gestation was
      greater than 37 weeks. Substrate zymography was used to qualitatively assess
      gelatinase and serine protease involvement. General protease activity (metallo,
      serine, acid and sulfhydryl) was measured quantitatively by fluorescent substrate
      cleavage. RESULTS: Substrate zymography revealed no active gelatinases or serine
      proteases. Fluorescent studies of general protease activity showed no significant
      difference between the groups and no significant regional variation. CONCLUSIONS:
      Gelatinase and serine protease activity do not play a major role in the formation
      of a membrane rupture initiation site or in prelabour membrane rupture at term.

PMID- 16806649
TI  - Interrelation of peri-operative morbidity and ASA class assignment in patients
      undergoing gynaecological surgery.
AB  - OBJECTIVE: The aim of this study was to estimate intra- and post-operative risk
      using the American Society of Anaesthesiologists (ASA) classification which is an
      important predictor of an intervention and of the entire operating programme.
      STUDY DESIGN: In this retrospective study, 4435 consecutive patients undergoing
      elective and emergency surgery at the Gynaecological Clinic of the University
      Hospital of Zurich were included. The ASA classification for pre-operative risk
      assessment was determined by an anaesthesiologist after a thorough physical
      examination. We observed several pre-, intra- and post-operative parameters, such
      as age, body-mass-index, duration of anaesthesia, duration of surgery, blood
      loss, duration of post-operative stay, complicated post-operative course,
      morbidity and mortality. The investigation of different risk factors was achieved
      by a multiple linear regression model for log-transformed duration of
      hospitalisation. RESULTS: Age and obesity were responsible for a higher ASA
      classification. ASA grade correlates with the duration of anaesthesia and the
      duration of the surgery itself. There was a significant difference in blood loss
      between ASA grades I (113+/-195 ml) and III (222+/-470 ml) and between classes II
      (176+/-432 ml) and III. The duration of post-operative hospitalisation could also
      be correlated with ASA class. ASA class I=1.7+/-3.0 days, ASA class II=3.6+/-4.3
      days, ASA class III=6.8+/-8.2 days, and ASA class IV=6.2+/-3.9 days. The mean
      post-operative in-hospital stay was 2.5+/-4.0 days without complications, and
      8.7+/-6.7 days with post-operative complications. Multiple linear regression
      model showed that not only the ASA classification contained an important
      information for the duration of hospitalisation. Parameters such as age, class of
      diagnosis, post-operative complications, etc. also have an influence on the
      duration of hospitalisation. CONCLUSION: This study shows that the ASA
      classification can be used as a good and early available predictor for the
      planning of an intervention in gynaecological surgery. The ASA classification
      helps the surgeon to assess the peri-operative risk profile of which important
      information can be derived for the planning of the operation programme.

PMID- 16806650
TI  - The effect of ICSI, maternal age, and embryonic stage on early clinical loss rate
      of twin versus singleton pregnancies.
AB  - OBJECTIVES: To compare early loss rates between twin and singleton pregnancies
      following ART. STUDY DESIGN: First-trimester sonography counted the number of
      embryos with positive heartbeat in women undergoing IVF/ICSI and transfer of one
      to three embryos. The number of lost pregnancies was calculated from a second
      trimester sonogram. Loss rates of the entire pregnancy were related to maternal
      age <38 or > or = 38 years, IVF or ICSI, and cleavage or blastocyst stage embryo
      transfers (in ICSI cases). RESULTS: Patients underwent IVF with (n = 672) and
      without (n = 189) ICSI. The overall odds of miscarrying the entire singleton
      pregnancy were 2.6 times that of a twin gestation (95% CI 1.5, 4.5). The
      disadvantage for singletons compared to twins seems more apparent in pregnancy
      after ICSI in the subgroup of patients <38 years (OR 2.9, 95% CI 1.5, 5.8). In
      this subgroup, the disadvantage conferred to singletons appeared only among days
      2-3 embryo transfers (OR 3.0, 95% CI 1.3, 7.2). CONCLUSION: A significantly lower
      early spontaneous loss rate of twin pregnancies seems related to ICSI followed by
      cleavage stage embryo transfer in patients <38 years.

PMID- 16806651
TI  - Awareness of hormonal emergency contraception among married women in a Kuwaiti
      family social network.
AB  - OBJECTIVE: Awareness and use of hormonal emergency contraception are not known in
      the Arab world. This study investigated awareness and perceptions of hormonal
      emergency contraception among women within a Kuwaiti extended family and their
      social contacts. STUDY DESIGN: A cross-sectional survey was conducted using a
      self-administered questionnaire which was distributed to 66 married women within
      a Kuwaiti family's social network. The questionnaire provided a short explanation
      of hormonal emergency contraception and then elicited the respondent's prior
      awareness, concerns and perception on future availability. RESULTS: The mean
      (S.D.) age of the respondents was 35.1 (6.3) years. Over 30% were currently using
      oral contraceptives; 28% were using no contraceptive method. Four women (6.1%)
      had heard of hormonal emergency contraception before, one had used it. Most
      respondents (65.2%) would not use or inform a friend about hormonal emergency
      contraception. Main concerns were risks to the health of the woman (83.3%) or the
      baby (54.5%) or that it was abortifacient (21.2%). However, 90.9% of respondents
      wanted hormonal emergency contraception to be available. CONCLUSIONS: Awareness
      of hormonal emergency contraception is low among Kuwaiti women. Despite some
      concerns, they feel it should be made available. Health care providers and
      policymakers should address this situation.

PMID- 16806653
TI  - Complications associated with caesarean delivery in a setting with high HIV
      prevalence rates.
AB  - OBJECTIVE: This study was designed to determine the prevalence of complications
      associated with abdominal delivery in a setting of high caesarean section (C/S)
      and HIV rates. METHOD: A detailed review of the records of 737 C/S performed over
      a three-month period was conducted in a tertiary teaching hospital in Durban,
      South Africa. RESULTS: The overall complication rate was 14.2%. Major
      complications included endometritis, wound sepsis, post-partum haemorrhage and
      bladder injury. HIV infection may have a negative impact on morbidity rates.
      Disimpacting the fetal head vaginally had a significant association with
      endometritis (p=0.021). The use of a corrugated drain did not prevent wound
      sepsis (p<0.001). CONCLUSION: Complications associated with C/S are common is a
      setting of high C/S rates and HIV infection.

PMID- 16806654
TI  - Gynaecological operations: do they improve sexual life?
AB  - Aim of the study was to determine if gynaecological operations have an effect on
      sexual function using the current medlined literature. We performed a Medline
      search using the terms "sexual life/function after operative gynaecological
      treatment", "sexual life/function after operations for gynaecological problems",
      "sexual life/function after hysterectomy", "sexual life/function, incontinence"
      and "sexual life/function, pelvic organ prolapse". Reviews were excluded. We
      divided the operations into four groups of (1) combined prolapse and incontinence
      operations, (2) prolapse operations only, (3) incontinence operations only and
      (4) hysterectomy and compared pre-to postoperative sexual outcome. Thirty-six
      articles including 4534 patients were identified. Only 13 studies used a
      validated questionnaire. The other authors used self-designed and non-validated
      questionnaires or orally posed questions by the examiner to determine sexual
      function. Prolapse operations particularly posterior repair using levator
      plication seem to deteriorate sexual function, incontinence procedure have some
      worsening effect on sexual function and hysterectomy seems to improve sexual
      function with no differences between subtotal or total hysterectomy.
      Gynaecological operations do influence sexual function. However, little validated
      data are available to come to this conclusion.

PMID- 16806655
TI  - Giant congenital scalp blue nevus, a neonatal case report.

PMID- 16806656
TI  - The incidence and characteristics of uterine bleeding during postoperative GnRH
      agonist treatment combined with tibolone add-back therapy in endometriosis
      patients of reproductive age.
AB  - OBJECTIVES: This study was undertaken to evaluate the incidence and the factors
      associated with uterine bleeding while taking GnRH agonist treatment combined
      with tibolone add-back therapy in endometriosis patients of reproductive age.
      STUDY DESIGN: The medical records of 188 endometriosis (stages III-IV) patients
      of reproductive age receiving postoperative GnRH agonist treatment combined with
      tibolone add-back therapy for 6 months were reviewed. Clinical features were
      analyzed and compared between the two groups: Group A, patients without an
      episode of uterine bleeding (n=137) and Group B, patients that had experienced
      uterine bleeding (n=51). RESULTS: Demographic profiles were not different in the
      two groups. The incidence of uterine bleeding was 27.1% and irregular spotting
      was the most frequent bleeding pattern. The proportion of patients who received
      ovarian surgery during pelviscopy was higher in Group B (p<0.05), but other
      clinical characteristics were not different between two groups. CONCLUSIONS: The
      incidence of uterine bleeding was 27.1%. And, the proportion of patients who
      received ovarian surgery was higher in patients with uterine bleeding.

PMID- 16806658
TI  - An approach based on spatial multicriteria analysis to map the nature
      conservation value of agricultural land.
AB  - Knowledge of the nature conservation value of agricultural land provides a useful
      input to land-use planning. However, the scarcity of suitable data causes this
      component to rarely play a role. The paper proposes a methodology based on
      commonly available data to assess the nature conservation value of agricultural
      landscapes, and to generate cartographic results to be used as decision variables
      in planning. The approach relies on landscape ecological indicators and on the
      application of multicriteria analysis in a Geographical Information System (GIS)
      context. Four criteria were selected: the agricultural landscape type, the cover
      of vegetation remnants and marginal features, the length of forest-agriculture
      ecotones, and the proximity to nature reserves. These criteria were assessed
      directly or by means of specific indicators, generating maps that were
      subsequently aggregated through spatial multicriteria analysis. The approach was
      tested in an alpine area located in Trentino (northern Italy).

PMID- 16806659
TI  - Comparative effect of Al, Se, and Mo toxicity on NO3(-) assimilation in sunflower
      (Helianthus annuus L.) plants.
AB  - Here, we study the effect caused by three trace elements--Al, Se, and Mo--applied
      at the same concentration (100 microM) and in their oxyanionic forms-
      NaAl(OH)(4), Na(2)SeO(4), and Na(2)MoO(4)--on NO(3)(-) assimilation (NO(3)(-),
      nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), and
      glutamate synthase (GOGAT) activities, and concentrations of amino acids and
      proteins) in sunflower (Helianthus annuus L. var. Kasol) plants. The most harmful
      element for sunflower plants proved to be selenate, followed by aluminate. On the
      contrary, the application of molybdate had no negative effect on the growth of
      this plant, suggesting the possibility of using sunflower for the
      phytoremediation of this metal, mainly in agricultural zones used for grazing
      where the excess of this element can provoke problems of molybdenosis in
      ruminants (particularly in cattle). In addition, we found that the alteration of
      NO(3)(-) assimilation by SeO(4)(2-) and Al(OH)(4)(-) directly influences the
      growth and development of plants, foliar inhibition of NR activity by SeO(4)(2-)
      being more harmful than the decrease in foliar availability of NO(3)(-) provoked
      by Al(OH)(4)(-).

PMID- 16806660
TI  - Use of artificial neural network black-box modeling for the prediction of
      wastewater treatment plants performance.
AB  - A reliable model for any wastewater treatment plant is essential in order to
      provide a tool for predicting its performance and to form a basis for controlling
      the operation of the process. This would minimize the operation costs and assess
      the stability of environmental balance. This process is complex and attains a
      high degree of nonlinearity due to the presence of bio-organic constituents that
      are difficult to model using mechanistic approaches. Predicting the plant
      operational parameters using conventional experimental techniques is also a time
      consuming step and is an obstacle in the way of efficient control of such
      processes. In this work, an artificial neural network (ANN) black-box modeling
      approach was used to acquire the knowledge base of a real wastewater plant and
      then used as a process model. The study signifies that the ANNs are capable of
      capturing the plant operation characteristics with a good degree of accuracy. A
      computer model is developed that incorporates the trained ANN plant model. The
      developed program is implemented and validated using plant-scale data obtained
      from a local wastewater treatment plant, namely the Doha West wastewater
      treatment plant (WWTP). It is used as a valuable performance assessment tool for
      plant operators and decision makers. The ANN model provided accurate predictions
      of the effluent stream, in terms of biological oxygen demand (BOD), chemical
      oxygen demand (COD) and total suspended solids (TSS) when using COD as an input
      in the crude supply stream. It can be said that the ANN predictions based on
      three crude supply inputs together, namely BOD, COD and TSS, resulted in better
      ANN predictions when using only one crude supply input. Graphical user interface
      representation of the ANN for the Doha West WWTP data is performed and presented.

PMID- 16806661
TI  - Decreased RECK expression indicating proteolytic imbalance in prostate cancer is
      associated with higher tumor aggressiveness and risk of prostate-specific antigen
      relapse after radical prostatectomy.
AB  - OBJECTIVES: Decreased expression of reversion-inducing cysteine-rich protein with
      Kazal motifs (RECK) was recently shown in several cancer types. To evaluate its
      potential role for prostate carcinoma, we investigated RECK expression in
      prostate cancer (pCA) samples. METHODS: RECK messenger RNA levels in 15
      microdissected normal/tumor matches were determined by quantitative reverse
      transcriptase-polymerase chain reaction. Protein expression of RECK was evaluated
      by immunohistochemical staining in tissue samples of adenomectomies (n=24) and
      pCA samples after radical prostatectomy (n=247). RECK expression was related to
      preoperative prostate-specific antigen (PSA), tumor stage and grade, surgical
      margin status, and PSA relapse-free time after radical prostatectomy. RESULTS:
      Consistent with lower RECK messenger RNA by 24%, RECK protein expression was
      decreased in pCA, compared with adjacent normal tissue and prostatic
      intraepithelial neoplasia. RECK expression in samples of benign prostatic
      hyperplasia from adenomectomy specimens was higher than in normal adjacent tissue
      of prostate carcinomas. Decreased RECK expression was associated with higher
      Gleason score (> or =7) and higher tumor stage. Multivariate analysis using the
      Cox proportional hazards model revealed that negative RECK expression was an
      independent prognostic factor for an increased risk of PSA relapse, especially in
      patients with higher tumor grades (Gleason score > or =7). CONCLUSIONS: Decreased
      RECK expression correlating with the aggressiveness of pCA and the PSA relapse
      free time could become an adjunct tissue biomarker to improve the follow-up and
      treatment decision for these pCA patients.

PMID- 16806662
TI  - A nomogram for staging of exclusive nonobturator lymph node metastases in men
      with localized prostate cancer.
AB  - OBJECTIVES: Some patients with localized prostate cancer are at risk of
      nonobturator lymph node invasion (NOLNI) and may require an extended pelvic lymph
      node dissection (ePLND). We explored the rate of exclusive NOLNI and developed a
      nomogram to predict it. MATERIAL AND METHODS: We mapped all ePLND specimens
      according to their anatomic location (obturator, external iliac, internal iliac
      lymph nodes) and assessed the location-specific rate of LNI in 565 patients. A
      multivariate logistic regression-based nomogram predicting NOLNI was then
      internally validated with 200 bootstrap resamples. RESULTS: Overall, 11.1% (63 of
      565) had LNI and 21 (3.7%) had exclusive NOLNI. The nomogram predicting exclusive
      NOLNI was 80.2% accurate. The nomogram's negative predictive value was 99%, when
      it predicted 0-10% probability of NOLNI. This approach could allow the omission
      of an ePLND in 350 of 565 (61.9%) patients and still correctly stage 85.8% of
      NOLNI cases. CONCLUSIONS: Our nomogram-based approach offers the possibility of
      identifying men who are at virtually zero risk of exclusive NOLNI. In these men,
      an ePLND may be safely avoided.

PMID- 16806663
TI  - Radical cystectomy and orthotopic bladder replacement in females.
AB  - INTRODUCTION: More than 15 years ago, several centers started to offer urethra
      sparing cystectomy and orthotopic urinary diversion for female patients with
      bladder malignancies. Several studies have been published, outlining both the
      anatomical and oncological aspects of such an approach. METHODS: In this
      contribution, the main aspects regarding the surgical technique of cystectomy and
      orthotopic urinary diversion in female patients, including technical variations
      which have been derived over the years, are presented. RESULTS AND CONCLUSION:
      The video shows a detailed description of the surgical technique, and the main
      steps of the procedure are demonstrated in schematic drawings as well as in
      animations to facilitate understanding. Emphasis is given on important anatomical
      and physiological aspects, which have influenced the current surgical steps.
      Possible sequelae on oncological and functional outcome, which play an important
      role in the evaluation of this procedure, are also discussed.

PMID- 16806664
TI  - Pattern of renal function deterioration as a predictive factor of unilateral
      ureteropelvic junction obstruction treatment.
AB  - OBJECTIVES: To assess the process of renal function deterioration in patients
      with unilateral ureteropelvic junction (UPJ) obstruction and its impact on their
      treatment course. MATERIAL AND METHODS: The files of patients treated for
      unilateral UPJ obstruction at our department from 1996 to 2003 were
      retrospectively reviewed. All patients were initially treated conservatively and
      followed up regularly. Criteria for conversion to surgical treatment were
      increase in anteroposterial renal pelvis diameter, increase in T(1/2) washout
      pattern, and drop of relative renal function (RRF) below 40% in diuretic
      renogram. Patients operated on because of multiple urinary infections, pelvic
      stones, or solitary kidneys were excluded. Patients were divided into group A,
      which included those whose treatment was converted from conservative to surgical,
      and group B in which patients were treated conservatively. All patients operated
      on underwent dismembered pyeloplasty. RESULTS: Sixty-four patients with grade
      three or four hydronephrosis in postnatal ultrasound examination and an
      obstructive pattern in diuretic renogram were studied. All group A patients
      (n=47) reached an RRF below 40%; in 41 (87.2%) deterioration of RRF was detected
      in at least two sequential follow-up studies. In group B patients (n=17),
      deterioration was also detected in seven (41.1%) patients in two sequential
      studies (p<0.0005), although the RRF never dropped below 40%. No differences in
      gender, side of obstruction, or frequency of follow-up were detected between the
      two groups. CONCLUSIONS: RRF deterioration and its progression for at least two
      sequential follow-ups could serve as a predictive factor for surgical treatment.

PMID- 16806665
TI  - Bulbar urethroplasty with dorsal onlay buccal mucosal graft and fibrin glue.
AB  - OBJECTIVES: We describe a new surgical technique with the use of fibrin glue for
      bulbar urethra reconstruction using a dorsal buccal mucosal onlay graft. METHODS:
      Six patients with a mean age of 43 yr underwent bulbar urethroplasty with dorsal
      onlay buccal mucosal graft and fibrin glue. The urethra was mobilised from the
      corpora cavernosa and opened along its dorsal surface. The buccal mucosal graft
      was applied on the corpora cavernosa using 2 ml of fibrin glue. Two interrupted
      polyglactin 5-0 sutures were used to fix the apices of the graft to the
      underlying albuginea of the corpora cavernosa. The urethra was rotated back to
      cover the graft and an adjunctive fibrin glue was injected over the urethra.
      RESULTS: The mean operative time was 100 min (range, 90-120 min). No
      intraoperative or postoperative complications were observed. Voiding
      cystourethrography was performed when the catheter was removed 2 wk after
      surgery. Urine culture, uroflowmetry, and urethrography were repeated after 6 and
      12 mo and annually thereafter. Mean follow-up was 16 mo (range, 12-24 mo). No
      restrictures at the anastomotic sites were demonstrated in any of the patients 6
      and 12 mo after surgery. CONCLUSIONS: The use of fibrin glue represents a slight
      but significant step toward perfecting the surgical technique of bulbar urethral
      reconstruction.

PMID- 16806666
TI  - The correlation between metabolic syndrome and prostatic growth in patients with
      benign prostatic hyperplasia.
AB  - OBJECTIVES: To evaluate the relationship between metabolic syndrome and annual
      prostatic growth rates in benign prostatic hyperplasia (BPH) patients. METHODS:
      The 78 BPH patients with lower urinary tract symptoms included in this
      prospective study were divided into two groups according to whether they had a
      diagnosis of metabolic syndrome. This diagnosis was made according to the most
      recent consensus report of the National Cholesterol Education Program's Third
      Adult Treatment Panel. Blood pressure, body weight, body height, and waist and
      hip circumferences were measured. The body mass index (BMI) and waist-to-hip
      ratio (WHR) were calculated. Biochemical analyses including serum glucose, total
      cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), insulin, and prostate-specific antigen
      (PSA) were performed. Total prostate (TP) volume and transitional zone (TZ)
      volume were measured by transrectal ultrasound. Annual TP and TZ growth rates
      were calculated. RESULTS: BPH patients with metabolic syndrome (first group) had
      significantly higher median body weight, BMI, serum glucose, serum triglyceride,
      and PSA levels but lower serum HDL-C level, compared with BPH patients without
      metabolic syndrome (second group, p<0.05). Median annual TP growth rate (1.0
      ml/yr) and median annual TZ growth rate (1.25 ml/yr) were significantly higher in
      the first group versus the second group (0.64 ml/yr and 0.93 ml/yr, respectively,
      p<0.05). CONCLUSIONS: The present study demonstrates a further increase in
      prostate growth in BPH patients with metabolic syndrome. Future studies are
      needed to confirm our results and to explain underlying mechanisms.

PMID- 16806667
TI  - Large-volume laparoscopic partial nephrectomy using the potassium-titanyl
      phosphate (KTP) laser in a survival porcine model.
AB  - OBJECTIVES: Laparoscopic partial nephrectomy (LPN) remains a technically
      challenging procedure primarily because of difficulties with hemostasis. In an
      attempt to develop a hemostatic cutting instrument for laparoscopic partial
      nephrectomy, we evaluated the potassium-titanyl-phosphate (KTP) laser for use
      during large-volume laparoscopic partial nephrectomy in a porcine model. METHODS:
      Transperitoneal lower pole laparoscopic partial nephrectomy was performed in six
      pigs. Two nonsurvival animals were used initially to develop the laser technique.
      Four animals underwent a right-sided laparoscopic laser partial nephrectomy
      followed by an identical left-sided procedure 2 weeks later. Renal hilar
      occlusion was used in all cases. A novel 365-mum end-firing laser fibre and 80-W
      KTP laser were used for resection and hemostasis. All renal remnants underwent
      retrograde pyelography and histologic examination. RESULTS: Laser resection and
      hemostasis was successfully completed in all cases, and no perioperative
      complications occurred. Mean estimated blood loss was 80 ml (25-250 ml). Mean
      laser and warm ischemia times were 35 and 34 minutes, respectively. Resection
      speed was limited by smoke formation but not by cutting or hemostatic efficiency
      of the laser. Mean resected kidney mass was 30 g or 25% of total kidney mass.
      There were no urinomas, but, on retrograde pyelogram, extravasation was noted in
      seven of eight kidneys (87.5%). CONCLUSIONS: The KTP laser provides hemostasis
      during large-volume resection in the porcine kidney. This technique appears
      promising for laparoscopic partial nephrectomy in humans.

PMID- 16806668
TI  - Kinetic analysis on the sensitivity of glucose- or glyoxal-induced LDL glycation
      to the inhibitory effect of Psidium guajava extract in a physiomimic system.
AB  - Experimentation with a physiomimic system and kinetic analysis exhibited four
      distinct reaction phases in LDL glycation despite of the type of inducer: glucose
      or glyoxal. LDL glycation was more sensitive to a status of hyperglycemia (such
      as 400 mg glucose/100 mL) as evidenced by the reaction order of 0.53. Glucose
      reacted intensively in the Initial Phase (reaction period 0-2h) which was
      identified to result from a parallel mechanism involving both the direct Schiff's
      product formation and the auto-oxidative cleavages. In contrast, a physiological
      level of glyoxal revealed merely a reaction order of only 0.09, implicitly
      indicating a far less sensitive glycation which can be attributed to a mechanism
      proceeding simply through a molecular Schiff's reaction. On treatment with
      Psidium guajava L. aqueous extract (PE) (0.01-0.625 mg/mL), a rather unique and
      significant inhibitory characteristic on LDL glycation was observed with a dose
      dependent manner. We attributed such an effect of PE to its distinct abundance of
      polyphenolic content (165.61+/-10.39 mggallic acid equivalent (GAE)/g).
      Conclusively, PE is an excellent anti-LDL glycative agent whose potential
      therapeutic uses can be extended to the prevention of a variety of cardiovascular
      and neurodegenerative diseases associated with glycations.

PMID- 16806669
TI  - Microtubules as mechanical force sensors.
AB  - Microtubules are polymers of tubulin subunits (dimers) arranged on a hexagonal
      lattice. Each tubulin dimer comprises two monomers, the alpha-tubulin and beta
      tubulin, and can be found in two states. In the first state a mobile negative
      charge is located into the alpha-tubulin monomer and in the second into the beta
      tubulin monomer. Each tubulin dimer is modeled as an electrical dipole coupled to
      its neighbors by electrostatic forces. The location of the mobile charge in each
      dimer depends on the location of the charges in the dimer's neighborhood.
      Mechanical forces that act on the microtubule affect the distances between the
      dimers and alter the electrostatic potential. Changes in this potential affect
      the mobile negative charge location in each dimer and the charge distribution in
      the microtubule. The net effect is that mechanical forces affect the charge
      distribution in microtubules. We propose to exploit this effect and use
      microtubules as mechanical force sensors. We model each dimer as a two-state
      quantum system and, following the quantum computation paradigm, we use discrete
      quantum random walk on the hexagonal microtubule lattice to determine the charge
      distribution. Different forces applied on the microtubule are modeled as
      different coin biases leading to different probability distributions of the
      quantum walker location, which are directly connected to different charge
      distributions. Simulation results show that there is a strong indication that
      microtubules can be used as mechanical force sensors and that they can also
      detect the force directions and magnitudes.

PMID- 16806670
TI  - Early development of visual recognition.
AB  - The most important ability of the human vision is object recognition, yet it is
      exactly the less understood aspect of the vision system. Computational models
      have been helpful in progressing towards an explanation of this obscure cognitive
      ability, and today it is possible to conceive more refined models, thanks to the
      new availability of neuroscientific data about the human visual cortex. This work
      proposes a model of the development of the object recognition capability, under a
      different perspective with respect to the most common approaches, with a precise
      theoretical epistemology. It is assumed that the main processing functions
      involved in recognition are not genetically determined and hardwired in the
      neural circuits, but are the result of interactions between epigenetic influences
      and the basic neural plasticity mechanisms. The model is organized in modules
      related with the main visual biological areas, and is implemented mainly using
      the LISSOM architecture, a recent self-organizing algorithm closely reflecting
      the essential behavior of cortical circuits.

PMID- 16806671
TI  - Gender-related psychological and behavioural correlates of pubertal timing in a
      national sample of Swiss adolescents.
AB  - The potential consequences of early and late puberty on the psychological and
      behavioural development of the adolescent are not well known. This paper presents
      focused analyses from the Swiss SMASH study, a self-administered questionnaire
      survey conducted among a representative sample of 7488 adolescents from 16 to 20
      years old. Data from participants reporting early or late timing of puberty were
      compared with those reporting average timing of maturation. Early maturing girls
      reported a higher rate of dissatisfaction with body image (OR=1.32) and
      functional symptoms (OR=1.52) and reported engaging in sexual activity more often
      (OR=1.93). Early maturing boys reported engaging in exploratory behaviours
      (sexual intercourse, legal and illegal substance use) at a significantly higher
      rate (OR varying between 1.4 and 1.99). Both early and late maturing boys
      reported higher rates of dysfunctional eating patterns (OR=1.59 and 1.38,
      respectively), victimisation (OR=1.61 and 1.37, respectively) and depressive
      symptoms (OR=2.11 and 1.53, respectively). Clinicians should take into account
      the pubertal stage of their patients and provide them, as well as their parents,
      with appropriate counselling in the field of mental health and health behaviour.

PMID- 16806672
TI  - Ligand-activated PPARbeta efficiently represses the induction of LXR-dependent
      promoter activity through competition with RXR.
AB  - Angiopoietin-like protein 3 (angptl3), a member of the vascular endothelial
      growth factor family, was shown to play an important role in regulating lipid
      metabolism. To elucidate the mechanism by which PPARbeta represses angptl3
      promoter activity, reporter constructs were prepared and transfection analysis
      carried out. PPARbeta repressed angptl3-Luc promoter activity and activation of
      PPARbeta by L-165041, a PPARbeta-specific ligand, increased the extent of
      repression. The repression by L-165041 was lost in angptl3-Luc plasmids having a
      deleted or mutated LXRalpha binding site (DR4). PPARbetaL405R, deficient in
      RXRalpha binding, had no effect on angptl3-Luc promoter activity. PPARbeta did
      not repress the activity of GAL4-LXRalpha which activates of GAL4DBD TK-Luc
      independent of RXR. Addition of RXRalpha completely abolished the repression of
      angptl3-Luc activity by PPARbeta. Mammalian two-hybrid analysis revealed that
      PPARbeta ligand binding enhanced the dissociation of the LXRalpha-RXRalpha
      heterodimer. Gel shift assays also indicated that PPARbeta ligand binding
      increased dissociation of LXRalpha/RXRalpha binding to a DR4 oligonucleotide
      probe; addition of RXRalpha restored the binding lost by addition of PPARbeta.
      Collectively, these results suggest that the binding of PPARbeta-specific ligand
      enhances the affinity between RXRalpha and activated PPARbeta and thus may
      regulate angptl3 gene expression through a DR4 element by competing with LXRalpha
      for RXRalpha.

PMID- 16806673
TI  - A novel peptide that selectively binds highly metastatic hepatocellular carcinoma
      cell surface is related to invasion and metastasis.
AB  - Using a phage display approach, we identified AWYPLPP peptide as a specific
      peptide ligand that binds to the cell surface of highly metastatic human
      hepatocellular carcinoma (HCC). Moreover, the peptide was able to promote in
      vitro invasion of highly metastatic HCC cells by activating matrix
      metalloproteinase-9 and in vivo lung metastasis of HCC tumors. These results
      indicate that AWYPLPP peptide likely recognizes a novel receptor that is
      selectively expressed on the cell surface of highly metastatic HCC and mediates
      cellular activities associated with the invasive phenotype. Identification of the
      receptor for the AWYPLPP peptide may provide new insights into the molecular
      mechanism of HCC metastasis.

PMID- 16806674
TI  - Retinoic acid receptor beta2 is epigenetically silenced either by DNA methylation
      or repressive histone modifications at the promoter in cervical cancer cells.
AB  - To elucidate the silencing mechanism of retinoic acid receptor beta2 (RAR beta2)
      in cervical carcinogenesis, we investigated RAR beta2 expression and the status
      of both DNA methylation and histone modifications at the promoter in cervical
      cancer cell lines. RAR beta2 was frequently repressed in cancer cell lines and in
      primary cancers of the cervix. Although the majority of RAR beta2-negative
      cancers had methylated promoter, RAR beta2 was repressed with hypomethylated
      promoter in a substantial fraction of the cancers. The RAR beta2-negative cells
      with hypomethylated promoters showed a repressive histone modification pattern at
      the promoter. RAR beta2 was reactivated by a histone deacetylase inhibitor,
      accompanied by formation of active histone modifications. The repressive
      modification was also observed in cells repressed with hypermethylated promoter,
      but RAR beta2 was reactivated only by DNA demethylating agent and not by histone
      deacetylase inhibitor. Our results suggest that RAR beta2 is silenced by either
      of the two key epigenetic pathways, DNA methylation or repressive histone
      modifications, depending on the individual cancer cells.

PMID- 16806675
TI  - Adsorptive removal of chlorophenols from aqueous solution by low cost adsorbent-
      Kinetics and isotherm analysis.
AB  - Adsorptive removal of parachlorophenol (PCP) and 2,4,6-trichlorophenol (TCP) from
      aqueous solutions by activated carbon prepared from coconut shell was studied and
      compared with activated carbon of commercial grade (CAC). Various chemical agents
      in different concentrations were used (KOH, NaOH, CaCO(3), H(3)PO(4) and ZnCl(2))
      for the preparation of coconut shell activated carbon. The coconut shell
      activated carbon (CSAC) prepared using KOH as chemical agent showed high surface
      area and best adsorption capacity and was chosen for further studies. Batch
      adsorption studies were conducted to evaluate the effect of various parameters
      such as pH, adsorbent dose, contact time and initial PCP and TCP concentration.
      Adsorption equilibrium reached earlier for CSAC than CAC for both PCP and TCP
      concentrations. Under optimized conditions the prepared activated carbon showed
      99.9% and 99.8% removal efficiency for PCP and TCP, respectively, where as the
      commercially activated carbon had 97.7% and 95.5% removal for PCP and TCP,
      respectively, for a solution concentration of 50mg/L. Adsorption followed pseudo
      second-order kinetics. The equilibrium adsorption data were analysed by Langmuir,
      Freundlich, Redlich-Peterson and Sips model using non-linear regression
      technique. Freundlich isotherms best fitted the data for adsorption equilibrium
      for both the compounds (PCP and TCP). Similarly, acidic pH was favorable for the
      adsorption of both PCP and TCP. Studies on pH effect and desorption revealed that
      chemisorption was involved in the adsorption process. The efficiency of the
      activated carbon prepared was also tested with real pulp and paper mill effluent.
      The removal efficiency using both the carbons were found highly satisfactory and
      was about 98.7% and 96.9% as phenol removal and 97.9% and 93.5% as AOX using CSAC
      and CAC, respectively.

PMID- 16806676
TI  - Photocatalytic decolorization of azo-dye with zinc oxide powder in an external UV
      light irradiation slurry photoreactor.
AB  - Photocatalytic decolorization of azo-dye Orange II in water has been examined in
      an external UV light irradiation slurry photoreactor using zinc oxide (ZnO) as a
      semiconductor photocatalyst. The effects of process parameters such as light
      intensity, initial dye concentration, photocatalyst loading and initial solution
      pH on the decolorization rate of Orange II have been systematically investigated.
      A two-stage photocatalytic decolorization of Orange II, the first stage of fast
      decolorization rate and the subsequent second stage of rather slow decolorization
      rate, was found. The efficiency of decolorization of Orange II increased as
      initial Orange II concentration decreased and UV light intensity increased. There
      was the optimal ZnO concentration being around 1000 mg L(-1). The optimal pH was
      around 7.7, which was at the natural pH of the dye solution. The effect of
      aeration rate on the decolorization of Orange II has been also investigated and
      the enhancement of decolorization of Orange II with increasing aeration rate was
      found. By using a model for the light intensity profile in the external UV light
      irradiation slurry photoreactor, the simulation model for the decolorization of
      Orange II with ZnO photocatalyst has been developed. The proposed model in which
      the slow decolorization in the second stage as well as the initial fast
      decolorization is also taken into account could simulate the experimental results
      for UV light irradiation satisfactorily. The proposed simulation model in which
      the change of light intensity with time due to the decolorization of Orange II
      and the light scatter due to solid photocatalysts are considered will be very
      useful for practical engineering design of the slurry photoreactor of wastewater
      including textile dyes.

PMID- 16806677
TI  - Kinetics of adsorption of dyes from aqueous solution using activated carbon
      prepared from waste apricot.
AB  - Adsorbent (WA11Zn5) has been prepared from waste apricot by chemical activation
      with ZnCl(2). Pore properties of the activated carbon such as BET surface area,
      pore volume, pore size distribution, and pore diameter were characterized by N(2)
      adsorption and DFT plus software. Adsorption of three dyes, namely, Methylene
      Blue (MB), Malachite Green (MG), Crystal Violet (CV), onto activated carbon in
      aqueous solution was studied in a batch system with respect to contact time,
      temperature. The kinetics of adsorption of MB, MG and CV have been discussed
      using six kinetic models, i.e., the pseudo-first-order model, the pseudo-second
      order model, the Elovich equation, the intraparticle diffusion model, the Bangham
      equation, the modified Freundlich equation. Kinetic parameters and correlation
      coefficients were determined. It was shown that the second-order kinetic equation
      could describe the adsorption kinetics for three dyes. The dyes uptake process
      was found to be controlled by external mass transfer at earlier stages (before 5
      min) and by intraparticle diffusion at later stages (after 5 min). Thermodynamic
      parameters, such as DeltaG, DeltaH and DeltaS, have been calculated by using the
      thermodynamic equilibrium coefficient obtained at different temperatures and
      concentrations. The thermodynamics of dyes-WA11Zn5 system indicates endothermic
      process.

PMID- 16806678
TI  - Flame atomic absorption spectrometric determination of trace quantities of
      cadmium in water samples after cloud point extraction in Triton X-114 without
      added chelating agents.
AB  - A new micell-mediated phase separation method for preconcentration of ultra-trace
      quantities of cadmium as a prior step to its determination by flame atomic
      absorption spectrometry has been developed. The method is based on the cloud
      point extraction (CPE) of cadmium in iodide media with Triton X-114 in the
      absence of any chelating agent. The optimal extraction and reaction conditions
      (e.g., acid concentration, iodide concentration, effect of time) were studied,
      and the analytical characteristics of the method (e.g., limit of detection,
      linear range, preconcentration, and improvement factors) were obtained. Linearity
      was obeyed in the range of 3-300 ng mL(-1) of cadmium. The detection limit of the
      method is 1.0 ng mL(-1) of cadmium. The interference effect of some anions and
      cations was also tested. The method was applied to the determination of cadmium
      in tap water, waste water, and sea water samples.

PMID- 16806679
TI  - Process development for the removal and recovery of hazardous dye erythrosine
      from wastewater by waste materials-Bottom Ash and De-Oiled Soya as adsorbents.
AB  - Erythrosine is a water-soluble xanthene class of dye. It is widely used as
      colorant in foods, textiles, drugs and cosmetics. It is highly toxic, causes
      various types of allergies, thyroid activities, carcinogenicity, DNA damage
      behaviour, neurotoxicity and xenoestrogen nature in the humans and animals. The
      photochemical and biochemical degradation of the erythrosine is not recommended
      due to formation of toxic by-products. The present paper is an attempt to remove
      erythrosine from wastewater using adsorption over Bottom Ash-a power plant waste
      and De-Oiled Soya-an agricultural waste. Under the batch studies, effect of
      concentration of dye, temperature, pH of the solution, dosage of adsorbents,
      sieve size of adsorbents, etc., have been studied for the uptake of the dye over
      both adsorbents. The adsorption process verifies Langmuir and Freundlich
      adsorption isotherms in both the cases and based on the data different
      thermodynamic parameters have been evaluated. Batch studies also include kinetic
      measurements, rate constant study, mass transfer behaviour and establishment of
      mechanistic pathway for both the cases. For the bulk removal of the dye column
      operations have been carried out and breakthrough capacities of the Bottom Ash
      and De-Oiled Soya columns have been calculated. Attempts have also been made for
      the recovery of the adsorbed dye from exhausted columns by eluting dilute NaOH
      and more than 90% of the dye was recovered.

PMID- 16806680
TI  - Pb(II) and Cd(II) removal from aqueous solutions by olive cake.
AB  - The removal of heavy metals from wastewater using olive cake as an adsorbent was
      investigated. The effect of the contact time, pH, temperature, and concentration
      of adsorbate on adsorption performance of olive cake for Pb(II) and Cd(II) ions
      were examined by batch method. Adsorption of Pb(II) and Cd(II) in aqueous
      solution onto olive cake was studied in single component. After establishing the
      optimum conditions, elution of these ions from the adsorbent surface was also
      examined. The optimum sorption conditions were determined for two elements.
      Maximum desorption of the Pb(II) and Cd(II) ions were found to be 95.92 and
      53.97% by 0.5M HNO(3) and 0.2M HCl, respectively. The morphological analysis of
      the olive cake was performed by the scanning electron microscopy (SEM).

PMID- 16806681
TI  - Decolorization of methyl orange by ozonation in combination with ultrasonic
      irradiation.
AB  - The combination of ultrasound and ozone for the decolorization of azo dye, methyl
      orange, was studied. The effect of ultrasonic power, ozone gas flow rate, gaseous
      ozone concentration, initial dye concentration, pH and hydroxyl radical scavenger
      on the decolorization of methyl orange was investigated. The results showed that
      the synergistic effect was achieved by combining ozone with ultrasonic
      irradiation for the decolorization of methyl orange. The synergistic effect was
      more significant when the system temperature was raised due to the heat effect of
      ultrasonic irradiation. The decolorization of methyl orange fits the pseudo first
      order kinetic model. The decolorization rate increased with the increase of
      ultrasonic power, ozone gas flow rate, gaseous ozone concentration. However, the
      decolorization rate decreased with the increasing initial dye concentration.
      Either pH or sodium carbonate has little effect on the decolorization rate,
      indicating that the low frequency ultrasound enhanced ozonation process for the
      decolorization of methyl orange is mainly a direct reaction rather than radical
      reaction.

PMID- 16806682
TI  - Electrochemical treatment of the effluent of a fine chemical manufacturing plant.
AB  - In this work, the electrochemical oxidation of an actual industrial wastewater
      with conductive-diamond anodes has been studied. The wastewater is the effluent
      of a fine chemicals plant. This effluent consists of an aqueous solution of
      solvents (ketones and alcohols) with a high concentration of aromatic compounds
      coming from the raw materials, intermediates and products of the different
      processes of the plant and its COD is around 6000 mg dm(-3). The electrolyses
      were carried out in a discontinuous operation mode under galvanostatic
      conditions, using a bench-scale plant equipped with a single compartment
      electrochemical flow cell. The conductive-diamond electrochemical oxidation
      (CDEO) allowed achieving the complete mineralization of the waste with high
      current efficiencies. These efficiencies seem to strongly depend on the
      concentration, pH and temperature but not on the current density (in the range
      studied). This confirms that besides the hydroxyl radicals mediated oxidation,
      CDEO combines other important oxidation processes such as the direct
      electrooxidation on the diamond surface and the oxidation mediated by other
      electrochemically formed compounds generated on this electrode. Other two
      advanced oxidation processes (ozonation and Fenton oxidation) have been also
      studied in this work for comparison purposes. Both technologies were able to
      treat the wastes, but they obtained very different results in terms of efficiency
      and mineralization. The efficiency of ozonation and electrochemical oxidation
      were very similar (especially during the first stages), although the energy
      consumption required by the electrochemical process to remove at fixed percentage
      of COD or TOC was significantly smaller than that of ozonation. The possible
      accumulation of carboxylic acid as final products excludes the use of Fenton
      oxidation as a sole treatment technology.

PMID- 16806683
TI  - An integrated technique using zero-valent iron and UV/H2O2 sequential process for
      complete decolorization and mineralization of C.I. Acid Black 24 wastewater.
AB  - The zero-valent iron (ZVI) reduction succeeds for decolorization, while
      UV/H(2)O(2) oxidation process results into mineralization, so that this study
      proposed an integrated technique by reduction coupling with oxidation process in
      order to acquire simultaneously complete both decolorization and mineralization
      of C.I. Acid Black 24. From the experimental data, the zero-valent iron addition
      alone can decolorize the dye wastewater yet it demanded longer time than ZVI
      coupled with UV/H(2)O(2) processes (Red-Ox). Moreover, it resulted into only
      about 30% removal of the total organic carbon (TOC), which was capable to be
      effectively mineralized by UV/H(2)O(2) process. The proposed sequential ZVI
      UV/H(2)O(2) integration system cannot only effectively remove color and TOC in AB
      24 wastewater simultaneously but also save irradiation power and time demand.
      Furthermore, the decolorization rate constants were about 3.77-4.0 times
      magnitude comparing with that by UV/H(2)O(2) process alone.

PMID- 16806684
TI  - The use of artificial neural networks (ANN) for modeling of decolorization of
      textile dye solution containing C. I. Basic Yellow 28 by electrocoagulation
      process.
AB  - In this paper, electrocoagulation has been used for removal of color from
      solution containing C. I. Basic Yellow 28. The effect of operational parameters
      such as current density, initial pH of the solution, time of electrolysis,
      initial dye concentration, distance between the electrodes, retention time and
      solution conductivity were studied in an attempt to reach higher removal
      efficiency. Our results showed that the increase of current density up to 80 Am(
      2) enhanced the color removal efficiency, the electrolysis time was 7 min and the
      range of pH was determined 5-8. It was found that for achieving a high color
      removal percent, the conductivity of the solution and the initial concentration
      of dye should be 10 mS cm(-1) and 50 mg l(-1), respectively. An artificial neural
      networks (ANN) model was developed to predict the performance of decolorization
      efficiency by EC process based on experimental data obtained in a laboratory
      batch reactor. A comparison between the predicted results of the designed ANN
      model and experimental data was also conducted. The model can describe the color
      removal percent under different conditions.

PMID- 16806685
TI  - Effect of hardness on acute toxicity of metal mixtures using Daphnia magna:
      prediction of acid mine drainage toxicity.
AB  - In this study, the effect of hardness on the combined outcome of metal mixtures
      was investigated using Daphnia magna. The toxic unit (TU) was calculated using
      modified LC(50) values based on the hardness (i.e., LC(50-soft) and LC(50-hard)).
      From a bioassay test, the degree of sensitivity to hardness on the toxicity
      changes was in the order: Cd<Cu<Zn<Pb, with 25, 66, 77 and 88% decreases in the
      LC(50) values, respectively, when the hard test solution was replaced with a soft
      test solution. In mixture toxicity tests, the difference in the test solution
      hardness was found to clearly cause different toxicities, as determined by the TU
      calculated by the LC(50-hard), using the toxicity of a standard culture medium as
      the reference. That is, approximately four to five times higher toxicity was
      observed in soft (i.e., 44+/-4 mg/L as CaCO(3)) rather than hard water (i.e.,
      150+/-10mg/L as CaCO(3)) test solutions. In the tests where the modified
      reference toxicity values (i.e., LC(50-soft) and LC(50-hard) for soft and hard
      test solution, respectively) obtained from the individual metal toxicity tests
      with different hardness were used to calculate the TU, the results showed very
      similar D. magna toxicities to those of the TU from the mixture of soft and hard
      test solutions, regardless of the hardness. According to the toxicity results of
      the mixture, the aquatic toxic effects of the acid mine drainage (AMD) collected
      from mine areas that contained metal mixtures were investigated using Daphnia
      magna and the modified LC(50) value of the TU hardness function calculated for
      varying solution hardness. The results of the biological WET test closely matched
      our overall prediction, with significant correlation, having a p-value of 0.513
      in one way ANOVA test (n=19). Therefore, this study revealed that the predicted
      toxicity of the metal mixture agreed well with the biological toxicity test when
      the modified LC(50) value was employed as the basis of hardness in the TU
      calculation.

PMID- 16806686
TI  - Environmental assessment of different photo-Fenton approaches for commercial
      reactive dye removal.
AB  - An environmental study using life cycle assessment (LCA) has been applied to
      three bench-scale wastewater treatments for Cibacron Red FN-R hetero-bireactive
      dye removal: artificial light photo-Fenton process, solar driven photo-Fenton
      process and artificial light photo-Fenton process coupled to a biological
      treatment. The study is focused on electricity and chemicals consumption,
      transports and atmosphere and water emissions generated by the different
      processes involved. Results show that the artificial light photo-Fenton process
      is the worst treatment in terms of environmental impact. On the other hand, both
      solar driven and coupled to biological photo-Fenton processes reduce
      significantly the environmental damage, although none can be identified as the
      best in all impact categories. The major environmental impact is attributed to
      the H2O2 consumption and to the electrical energy consumption to run the UVA
      lamp. An economic analysis of the different photo-Fenton processes has also been
      performed and the results are discussed together with those obtained from the
      environmental assessment.

PMID- 16806687
TI  - Sorbent extraction of rubeanic acid-metal chelates on a new adsorbent: Sepabeads
      SP70.
AB  - A sorbent extraction procedure for lead, iron, cadmium and manganese ions on
      Sepabeads SP70 adsorption resin has been presented prior to their flame atomic
      absorption spectrometric determinations. By the passage of aqueous samples
      including analyte ions-rubeanic acid chelates through Sepabeads SP70 column,
      metal chelates adsorb quantitatively and almost all matrix elements will pass
      through the column to drain. The influence of potential interfering ions was also
      studied. The validation of the method was made though the analysis of LGC 6010
      Hard drinking water, SRM 1577b Bovine liver and GBW 07603 Bush branches and
      leaves standard reference materials (SRM). The method was applied to the
      determination of analyte ions from various water, wastewater, cow meat and milk,
      red wine, and tobacco samples with successfully results.

PMID- 16806688
TI  - Biodegradation of phenol and sodium salicylate mixtures by suspended Pseudomonas
      putida CCRC 14365.
AB  - The biodegradation of single phenol and sodium salicylate (SA) and their binary
      mixtures in water by free Pseudomonas putida (P. putida) CCRC 14365 was
      experimentally studied at 30 degrees C and pH 7. The initial concentration of the
      cells, adapted with either phenol or SA, was maintained at 0.025 g/L. Single
      substrate experiments were performed in the substrate level range 0.53-3.18 mM.
      The Haldane model has shown that phenol was biodegraded more quickly
      (mu(max)=0.245 h(-1)) than SA (0.137 h(-1)) under the ranges studied, and SA had
      a more inhibitory effect on cell growth (K(I)=5.21 mM) than phenol (12.6 mM) at
      low substrate levels even by SA-adapted cells. Binary substrate experiments were
      carried out at two fixed total substrate levels of 1.06 and 3.18 mM, with a
      varying molar concentration ratio of 0.33-3.0. The presence of a small amount of
      phenol to SA could significantly enhance the biodegradation of SA, particularly
      when the phenol-adapted cells were employed. On the other hand, the addition of a
      small amount of SA to phenol would retard the biodegradation of phenol,
      especially at higher total substrate levels (3.18 mM).

PMID- 16806689
TI  - Detonation temperature of high explosives from structural parameters.
AB  - A new scheme is introduced for calculating detonation temperature of different
      classes of high explosives. The ratio of oxygen to carbon and hydrogen to oxygen
      as well as specific structural parameters are the fundamental factors in the new
      method. An empirical new correlation is used to calculate detonation temperature
      of energetic compounds without considering heat contents of explosives and
      detonation products. Calculated detonation temperatures for both pure and
      explosive formulations show good agreement with respect to measured detonation
      temperatures and complicated computer code using BKWR and BKWS equations of
      state. Predicted detonation temperatures have root-mean-square (rms) percent
      deviation of 4.6, 14.2 and 4.6 from measured values for new method, BKWR and BKWS
      equations of state, respectively.

PMID- 16806690
TI  - Sulfidation treatment of copper-containing plating sludge towards copper resource
      recovery.
AB  - The present study is concerned with the sulfidation treatment of copper
      containing plating sludge towards copper resource recovery by flotation of copper
      sulfide from treated sludge. The sulfidation treatment was carried out by
      contacting simulated or real copper plating sludge with Na(2)S solution for a
      period of 5 min to 24 h. The initial molar ratio of S(2-) to Cu(2+) (S(2-) to
      Me(2+) in the case of real sludge) was adjusted to 1.00, 1.25 or 1.50, while the
      solid to liquid ratio was set at 1:50. As a result, it was found that copper
      compounds were converted to various copper sulfides within the first 5 min. In
      the case of simulated copper sludge, CuS was identified as the main sulfidation
      product at the molar ratio of S(2-) to Cu(2+) of 1.00, while Cu(7)S(4) (Roxbyite)
      was mainly found at the molar ratios of S(2-) to Cu(2+) of 1.50 and 1.25. Based
      on the measurements of oxidation-reduction potential, the formation of either CuS
      or Cu(7)S(4) at different S(2-) to Cu(2+) molar ratios was attributed to the
      changes in the oxidation-reduction potential. By contrast, in the case of
      sulfidation treatment of real copper sludge, CuS was predominantly formed,
      irrespective of S(2-) to Me(2+) molar ratio.

PMID- 16806691
TI  - Obestatin alters sleep in rats.
AB  - Obestatin is a recently identified peptide derived from the ghrelin gene. Ghrelin
      stimulates food intake whereas obestatin has an opposite effect in rats. Previous
      experiments in our laboratory revealed that ghrelin also induces wakefulness in
      rats. The aim of the present experiments was to study the effect of obestatin on
      sleep. Rats received intraperitoneal (n = 7; 16 or 64 microg/kg) or
      intracerebroventricular (i.c.v.; n = 11) injection of pyrogen-free isotonic NaCl
      or obestatin (1, 4 and 16 microg in a volume of 4 microl) at dark onset. Sleep
      wake activity was recorded for 23 h. I.c.v. administration of 16 microg obestatin
      induced a significant increase (approximately 58%) in the time spent in non-rapid
      eye-movement sleep (NREMS) in the first hour after the injection. This resulted
      from an increase in the number of NREMS episodes and shortened sleep latency.
      Electroencephalographic (EEG) slow-wave activity (0.5-4 Hz) was reduced by
      obestatin treatment. The initial increase in NREMS time was followed by a
      decrease in both NREMS and REMS in the second hour after the injection.
      Peripheral injection of obestatin did not induce significant changes in sleep in
      any post-injection hours. Results suggest that the sleep-promoting effect of
      centrally administered obestatin may be part of the behavioral manifestation of
      satiety elicited by the peptide. Current results confirm the finding that two
      regulatory peptides derived from the same gene have opposite actions in the same
      species.

PMID- 16806692
TI  - Selective alteration of expression of Na+/Ca2+ exchanger isoforms after transient
      focal cerebral ischemia in rats.
AB  - The Na+/Ca2+ exchanger (NCX) is an antiporter located in the plasma membrane of
      many cells, which can maintain the intracellular Ca(2+) homeostasis. Some studies
      have shown the close relationship of NCX and cerebral ischemia. But controversial
      results were obtained. Three NCX isoforms, NCX1, NCX2, and NCX3 were distributed
      selectively in central nervous system, which suggests that each isoform may have
      different function in cerebral ischemia. In this study we investigated the time
      related alteration of gene and protein expressions of NCX1, NCX2, and NCX3 in rat
      brain cortex after 2 h of transient middle cerebral artery occlusion (tMCAO).
      Reverse transcription-polymerase chain reaction (RT-PCR) was used to investigate
      the mRNA levels of each NCX isoform at 2, 6, 12, and 24 h of reperfusion,
      respectively. Western blot was used to measure the protein expressions of each
      NCX isoform at 2, 12, and 24 h of reperfusion, respectively. The results showed
      that NCX1 mRNA level was reduced by 42.1% and 27.8%, respectively, at 2 and 6h of
      reperfusion and restored to normal level at 12 and 24 h of reperfusion. NCX1
      protein was decreased by 36.6% at 2 h of reperfusion and recovered at 12 and 24 h
      of reperfusion. The mRNA and protein levels of NCX2 and NCX3 did not change
      significantly over time. These results suggest that NCX1 might play an important
      role in transient focal cerebral ischemia.

PMID- 16806693
TI  - Morphometry of otoliths in chicken macula lagena.
AB  - The macula lagena located at the apical end of the cochlea in birds is
      characterized by the presence of numerous otoliths with unclear sensory
      functions. These otoliths are reported to be similar to those in the vestibular
      system but their detailed features in morphology are unknown. In the present
      study, we examined the number, size and shape of otoliths from the macula lagena
      in Chinese domestic chickens (Gallus Ling Nan) with a scanning electron
      microscope for morphometry. For chickens aged 10-15 post-hatch days, the otoliths
      in each macula lagena were counted to be 16,055 +/- 4038 (mean +/- S.D., n = 4).
      The average length and width were 12.98 +/- 3.70 microm and 5.10 +/- 1.48 microm
      (n = 526 otoliths), respectively. The ratio of length to width for the otolith
      was 2.58 +/- 0.39 (n = 526 otoliths) and remained relatively constant despite
      their variations in physical size. Almost all the otoliths were in regular shape
      and appeared like isolated cylinders with smooth facets at each end, but a few of
      them (0.025% of 64,221 otoliths screened) were found to be in odd shapes, such as
      T-shape and cross-shape. The results suggest that otoliths in the macula lagena
      and those in the vestibular system of bird's inner ear have similar physical
      properties and may play a similar role in sensing gravitational and acceleration
      signals.

PMID- 16806694
TI  - Alpinia protocatechuic acid protects against oxidative damage in vitro and
      reduces oxidative stress in vivo.
AB  - In this study, the neuroprotective effects of Alpinia protocatechuic acid (PCA),
      a phenolic compound isolated from the dried fruits of Alpinia Oxyphylla Miq. was
      found. The protective effect of Alpinia PCA against H2O2-induced oxidative damage
      on PC12 cells was investigated by measuring cell viability via 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate
      dehydrogenase (LDH) assays. Rats were injected intraperitoneally with Alpinia PCA
      at a dose of 5mg/kg per day for 7 days, behavioral testing was performed in Y
      maze. In order to make clear the neuroprotective mechanism of Alpinia PCA, the
      activities of endogenous antioxidants and the content of lipid peroxide in brain
      were assayed. The results proved that Alpinia PCA significantly prevented the
      H2O2-induced reduction in cell survival, improved the cognition of aged rats,
      reduced the content of lipid peroxide, increased the activity of glutathione
      peroxidase and superoxide dismutase. All these suggested that Alpinia PCA was a
      potential neuroprotective agent and its neuroprotective effects were achieved at
      least partly by promoting endogenous antioxidant enzymatic activities and
      inhibiting free radical generation.

PMID- 16806695
TI  - Age-related changes in the frequency profile of children's finger tremor.
AB  - Little consensus exists as to the age-related pattern of change in the frequency
      characteristics of postural tremor through childhood. We investigated postural
      finger tremor of children (6 and 10 years) and adults (18-22 years) using
      accelerometers under dual and single limb conditions (10s trials). The postural
      tremor of the children exhibited proportionally more power below 10 Hz and less
      power above 20 Hz than that of the adults. It also showed a significantly lower
      peak frequency and lower proportion of power at the peak frequency than the
      adults in the 15-30 Hz frequency band but did not differ significantly from the
      adults in peak frequency or proportion of power at the peak frequency in the 5-15
      Hz frequency band. The greater relative contribution of fast time scales over the
      1-30 Hz frequency band in the organization of the postural tremor of the adults
      in comparison to the children may be a contributing factor to adult's typically
      observed reduced motor skill performance variability.

PMID- 16806696
TI  - Regional scalp EEG slow-wave synchronization during sleep cyclic alternating
      pattern A1 subtypes.
AB  - The levels of EEG synchronization, in the 0.25-2.5 Hz band, during the A1
      subtypes of the sleep "cyclic alternating pattern" (CAP) were measured in five
      healthy subjects by means of the synchronization likelihood (SL) algorithm. SL
      was measured for seven electrode pairs (F4-F3, C4-C3, P4-P3 for the analysis of
      interhemispheric SL and F4-C4, C4-P4, F3-C3, and C3-P3, for the analysis of
      intrahemispheric SL). During the A1 CAP subtypes, SL tended to be highest between
      pairs of electrodes situated over different hemispheres; in particular, SL
      obtained from F4-F3 was the highest, followed by that of P4-P3. These results
      indicate that the transient high level of synchronization in the slow-wave EEG
      range, during the sleep A1 CAP subtypes, is a phenomenon involving mostly the
      anterior parts of the brain and is probably based on interhemispheric
      interactions, possibly mediated by transcallosal connections.

PMID- 16806697
TI  - Polymorphisms in the DNA repair genes XPD (ERCC2) and XPF (ERCC4) are not
      associated with sporadic late-onset Alzheimer's disease.
AB  - Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair,
      recognizing and dealing a variety of helix-distorting lesions. Xeroderma
      pigmentosum group D (XPD) and group F (XPF) are essential participants in NER
      pathway. There is evidence that two common polymorphisms of XPD gene (g.22541C>A;
      exon 6 and g.35931A>C; Lys>Gln; exon 23) may be associated with differential DNA
      repair activities. Alzheimer's disease (AD) is characterized by progressive
      neuronal loss correlated in time with the symptoms of disease considered.
      Although deficient DNA repair was proposed in the etiology of AD by several
      researchers, polymorphisms of DNA repair genes have not been studied in AD yet.
      We conducted a case-control study including 97 patients with AD and age- and sex
      matched 101 control subjects to examine the role of genetic polymorphisms of XPD
      and XPF (g.30028T>C; exon 11) as a risk factor for AD. The frequencies of the
      XPD/exon 6, XPD/exon 23, and XPF/exon 11 variant alleles in our control group
      were 0.41, 0.35, and 0.35, respectively. No significant association was observed
      between the variant alleles of XPD/exon 6 (OR=0.94, 95% CI=0.63-1.41), XPD/exon
      23 (OR=1.24, 95% CI=0.82-1.86) and XPF/exon 11 (OR=1.08, 95% CI=0.72-1.64) and
      AD. Our results suggest that the polymorphic variants of these NER genes do not
      contribute to the risk of developing AD.

PMID- 16806698
TI  - Protective effect of quercetin, a natural flavonoid against neuronal damage after
      transient global cerebral ischemia.
AB  - Previous studies have demonstrated that quercetin, a bioflavonoid shows the
      inhibitory effect against ischemia and reperfusion-induced injury in various
      tissues including neural tissue. Quercetin is also reported to have an inhibitory
      effect against matrix metalloproteinases (MMPs). Because MMPs are known to play a
      main role in the pathophysiology of brain ischemic insult, their mechanisms of
      possible protective effect of quercetin against brain ischemia remain to be
      clarified. In the present study, C57BL/6 mice were subjected to 20 min transient
      global brain ischemia. Cerebral blood flow was monitored by laser doppler
      flowmeter. Animals were sacrificed 72 h after ischemia. Quercetin (50 mg/kg,
      dissolved in saline) was intraperitoneally administered to mice at 30 min before
      and immediately after ischemia and from the second day, quercetin was then
      administered once daily until sacrifice. The present study was undertaken to test
      the effect of quercetin on neuronal damage after transient cerebral ischemia.
      Neuronal damages were remarkable in the medial portion of CA1 and CA2 areas after
      ischemic insult. In quercetin-treated mice, delayed neuronal damage was
      significantly decreased compared with vehicle-treated mice. Mice treated with
      quercetin showed attenuated brain MMP-9 activity. Gelatin gel zymography showed
      an induction of MMP-9 protein after ischemia. Quercetin significantly inhibited
      ischemia-induced elevation of MMP-9. In situ zymography showed elevations in
      gelatinase activities after brain ischemia. Quercetin also inhibited TdT-mediated
      dUTP nick end labeling (TUNEL) staining in CA1 and CA2 areas. These results
      demonstrate that quercetin, a natural flavonoid reduces global ischemia-induced
      neuronal damage through inhibition of MMP-9 activity.

PMID- 16806699
TI  - Ventriloquism aftereffects occur in the rear hemisphere.
AB  - After exposure to a consistent spatial disparity of auditory and visual stimuli,
      subjective localization of sound sources is usually shifted in the direction of
      the visual stimuli. This study investigates whether such aftereffects can be
      observed in humans after exposure to a conflicting bimodal stimulation in virtual
      reality and whether these aftereffects are confined to the trained locations.
      Fourteen subjects participated in an adaptation experiment, in which auditory
      stimuli were convolved with non-individual head-related transfer functions,
      delivered via headphones. First, we assessed the auditory localization of
      subjects in darkness. They indicated the perceived direction of a sound using an
      angular pointer. We then immersed the subjects in a virtual environment by means
      of a head-mounted display. They were asked to reproduce sequences of movements of
      virtual objects with a mouse click on the objects. However, we introduced a
      spatial disparity of 15 degrees between the visual event and the concurrent
      auditory stimulation. After 20 min of exposure, we tested the subjects again in
      total darkness to determine whether their auditory localization system had been
      modified by the conflicting visual signals. We observed a shift of subjective
      localization towards the left in both dorsal and frontal hemifields of the
      subject, mainly for auditory stimuli located in the right hemispace. This result
      suggests that interaural difference cues and monaural spectral cues were not
      equally adapted, and that visual stimuli mainly influence the processing of
      binaural directional cues of sound localization.

PMID- 16806700
TI  - Immunofluorescence analysis of the expression of Norpeg (Rai14) in retinal Muller
      and ganglion cells.
AB  - Novel retinal pigment epithelial cell gene (Norpeg, Rai14), a developmentally
      regulated mouse gene, encodes a protein containing six ankyrin repeats and a
      coiled-coil domain. The objective of the present study was to characterize the
      Norpeg protein and to analyze its expression in mouse retina using an antibody
      preparation that we developed. The approximately 110kDa Norpeg was
      immunoprecipitated and characterized by mass spectrometry. Primary cultures of
      Muller and ganglion cells isolated from the mouse retina were found to express
      Norpeg when analyzed by immunoblotting and immunofluorescence microscopy.
      Immunofluorescence analysis of normal mouse retina sections demonstrated that
      Norpeg is expressed in cells of the ganglion cell layer, inner nuclear layer as
      well as in the retinal pigment epithelium. Immunoreactivity was also evident in
      the radial glial (Muller) cell fibers.

PMID- 16806701
TI  - Touch down: the effect of artificial touch cues on orientation in microgravity.
AB  - Orienting oneself in space is not an easy task. On Earth, we combine visual,
      vestibular and pressure cues into a coherent concept of up and down. Since there
      are no cues from gravity in space, astronauts have to adjust the way they
      determine up from down, with the possible risk of space motion sickness. In three
      tasks performed by one astronaut in the International Space Station (ISS), we
      examined the effect of artificial touch cues presented to the torso. The role of
      "natural" touch cues on spatial orientation in microgravity, such as pressure
      presented to the sole of the feet, has already been shown, but it is not trivial
      whether the brain can also integrate artificial orientation information that has
      no real life equivalent. We find that artificial touch information in the form of
      a localised vibration on the torso that indicates down can make orienting in
      microgravity faster, better and easier. The importance of the artificial touch
      information seems to increase over the initial 7 days of staying in microgravity
      while the weight of visual information decreases over the same period. The
      results underline the capacity of the brain to adapt to unusual environments and
      to use and integrate artificial cues. Besides astronauts, pilots, divers and
      people with a vestibular dysfunction may benefit from this technology.

PMID- 16806702
TI  - The inhibition of stuttering via the presentation of natural speech and
      sinusoidal speech analogs.
AB  - Sensory signals containing speech or gestural (articulatory) information (e.g.,
      choral speech) have repeatedly been found to be highly effective inhibitors of
      stuttering. Sine wave analogs of speech consist of a trio of changing pure tones
      representative of formant frequencies. They are otherwise devoid of traditional
      speech cues, yet have proven to evoke consistent linguistic percepts in
      listeners. Thus, we investigated the potency of sinusoidal speech for inhibiting
      stuttering. Ten adults who stutter read while listening to (a) forward-flowing
      natural speech; (b) forward-flowing sinusoid analogs of natural speech; (c)
      reversed natural speech; (d) reversed sinusoid analogs of natural speech; and (e)
      a continuous 1000 Hz pure tone. The levels of stuttering inhibition achieved
      using the sinusoidal stimuli were potent and not significantly different from
      those achieved using natural speech (approximately 50% in forward conditions and
      approximately 25% in the reversed conditions), suggesting that the patterns of
      undulating pure tones are sufficient to endow sinusoidal sentences with 'quasi
      gestural' qualities. These data highlight the sensitivity of a specialized
      'phonetic module' for extracting gestural information from sensory stimuli.
      Stuttering inhibition is thought to occur when perceived gestural information
      facilitates fluent productions via the engagement of mirror neurons (e.g., in
      Broca's area), which appear to play a crucial role in our ability to perceive and
      produce speech.

PMID- 16806703
TI  - Expression of ubiquitin and proteasome in motorneurons and astrocytes of spinal
      cords from patients with amyotrophic lateral sclerosis.
AB  - Proteasome, ubiquitin, GFAP and neurofilament were evaluated in motorneurons and
      astrocytes of spinal cords of ALS and control cases. ALS neurons exhibited
      ubiquitin positive inclusions and areas of strong immunoreaction for proteasome.
      Areas of proteasome stain were observed close to neurofilament positive proximal
      process enlargement. The percentage of neurons strongly immunoreacted, for
      proteasome was higher in ALS cases than in controls. Many astrocytes were
      positive for ubiquitin and proteasome. These results suggest that the ubiquitin
      proteasome pathway is involved in the ALS pathogenesis and agree with the view
      that ALS is a disorder of protein aggregation that affects neurons and
      nonneuronal cells.

PMID- 16806704
TI  - Selective migration and engraftment of bone marrow mesenchymal stem cells in rat
      lumbar dorsal root ganglia after sciatic nerve constriction.
AB  - Bone marrow mesenchymal stem cells (MSCs) preferentially migrate to the injured
      hemisphere when administered intravenously to rats with traumatic or ischemic
      brain injuries. In this study, we have investigated the localization of MSCs
      injected into the lumbar-4 dorsal root ganglion (L4-DRG) of rats with a sciatic
      nerve single ligature nerve constriction (SLNC). MSCs were isolated by their
      adherence to plastic, cultured until confluence and labelled with Hoechst.
      Animals with a unilateral injection of MSCs were subjected to an ipsilateral,
      bilateral or contralateral SLNC. After 9 days, they were perfused and the lumbar
      DRGs were dissected out, cut in a cryostat and observed with a fluorescence
      microscope. Large numbers of Hoechst-positive cells were observed in the injected
      L4-DRG, distributed around primary afferent neurons, resembling the anatomical
      localization of glial cells. In animals with an ipsilateral SLNC, some cells were
      detected in the ipsilateral L3, L5 or L6-DRGs but not in the contralateral
      ganglia. In animals with a bilateral lesion, MSCs migrated to both the
      ipsilateral and contralateral DRGs whereas in animals with a contralateral
      ligature, MSCs migrated to the contralateral DRGs. These results suggest that
      MSCs preferentially engraft in DRGs hosting primary sensory neurons affected by a
      lesion of their peripheral branches. Further studies should be carried out in
      order to elucidate the molecular mechanisms involved in this migration and
      homing, in order to evaluate the possible use of MSCs as a new therapeutic
      strategy for the treatment of peripheral nerve neuropathies.

PMID- 16806705
TI  - Inhibition of the spinal phosphoinositide 3-kinase exacerbates morphine
      withdrawal response.
AB  - The present study investigates the roles of the spinal phosphoinositide 3-kinase
      (PI3K) signaling pathway in naloxone-precipitated withdrawal in acute and chronic
      morphine-dependent mice. There are two principal findings: (1) intrathecal
      pretreatment with wortmannin or LY294002, two structurally unrelated PI3K
      inhibitors, produced a dose-dependent increase of naloxone-precipitated
      withdrawal jumping, which was accompanied by an increased expression of spinal
      Fos protein in acute and chronic morphine-dependent mice; and (2) the expression
      of spinal p110gamma, the catalytic subunit PI3K, in the membrane fraction was
      significantly down-regulated by naloxone-precipitated withdrawal in acute and
      chronic morphine-dependent mice. This study provides new evidence showing that
      inactivation of the PI3K signaling pathway in the spinal cord may be involved in
      the expression of morphine withdrawal.

PMID- 16806706
TI  - CSF -neurofilament correlates with outcome after aneurysmal subarachnoid
      hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event. Following the
      bleeding, a number of pathophysiological changes and clinical factors determine
      outcome. Not surprisingly, attempts to predict outcome based on a single factor
      have failed. The neurological status graded at admission to hospital and
      distributions of the blood on CT are the strongest predictors. There is evidence
      that cerebrospinal fluid (CSF) proteins may serve as markers of the extent of
      brain damage. The present study is focused on the light unit of neurofilament
      protein (NFL), previously not evaluated in aSAH. Lumbar puncture (LP),
      neurological grading according to World Federation of Neurological Surgeons
      (WFNS) and neurological examination according to the National Institute of Health
      Stroke Scale (NIHSS) were performed in 48 consecutive patients with aSAH 10-14
      days after the hemorrhage. CSF-NFL concentrations were analyzed using an ELISA.
      Outcome was assessed after 1 year and categorised according to the extended
      Glasgow Outcome Scale (GOSE). A significant correlation between CSF-NFL and GOSE
      was detected at follow up after 1 year. CSF-NFL also correlated with WFNS and
      NIHSS on the day of the lumbar puncture. CSF-NFL is a biochemical marker of brain
      damage correlating to neurological status and long-term outcome after aneurysmal
      subarachnoid hemorrhage.

PMID- 16806707
TI  - Spinal nerve lesion alters blood-spinal cord barrier function and activates
      astrocytes in the rat.
AB  - Alterations in the spinal cord microenvironment in a neuropathic pain model in
      rats comprising right L-4 spinal nerve lesion were examined following 1, 2, 4 and
      10 weeks using albumin and glial fibrillary acidic protein (GFAP)
      immunoreactivity. Rats subjected to nerve lesion showed pronounced activation of
      GFAP indicating astrocyte activation, and exhibited marked leakage of albumin,
      suggesting defects of the blood-spinal cord barrier (BSCB) function in the
      corresponding spinal cord segment. The intensities of these changes were most
      prominent in the gray matter of the lesioned side compared to the contralateral
      cord in both the dorsal and ventral horns. The most marked changes in albumin and
      GFAP immunoreaction were seen after 2 weeks and persisted with mild intensities
      even after 10 weeks. Distortion of nerve cells, loss of neurons and general
      sponginess were evident in the gray matter of the spinal cord corresponding to
      the lesion side. These nerve cell and glial cell changes was mainly evident in
      the areas showing leakage of endogenous albumin in the spinal cord. These novel
      observations indicate that chronic nerve lesion has the capacity to induce a
      selective increase in local BSCB permeability that could be instrumental in nerve
      cell and glial cell activation. These findings may be relevant to our current
      understanding on the pathophysiology of neuropathic pain.

PMID- 16806708
TI  - The influence of prognostic factors on neck pain intensity, disability, anxiety
      and depression over a 2-year period in subjects with acute whiplash injury.
AB  - The influence of potential prognostic factors (occupant- and crash-related
      factors, initial neck pain intensity and headache, whiplash injury severity,
      helplessness, locus of control, socioeconomic status) on neck pain intensity
      (VAS), disability (DRI), anxiety and depression (HADS) was estimated in a cohort
      of 3704 subjects with whiplash injury following a motor vehicle crash.
      Questionnaires were administered (baseline, 1-, 6-, 12-, 24-month follow-ups).
      VAS was trichotomized; "low" (0-30), "moderate" (31-54), "severe" (55-100). A
      cumulative logit model with a proportional odds assumption was applied. Results
      regarding depression differed somewhat from the other outcomes. Overall, initial
      neck pain intensity was an important prognostic factor, but acted also as an
      evident effect modifier. Females had slightly increased odds for all outcomes but
      depression, for which no gender differences were shown. Injury severity was
      associated with all outcomes, but was most pronounced regarding disability among
      those who perceived numbness/pain in arms/hands and also had severe initial neck
      pain (proportional odds ratio [OR] 6.5; 95% confidence interval [CI] 2.5-17.0).
      Initial headache influenced all outcomes. Income was not related to any of the
      outcomes, whereas a lower level of education was associated with all outcomes but
      depression. Locus of control was not a factor of importance. In contrast,
      helplessness was related to all outcomes, but was most pronounced regarding neck
      pain intensity and depression for subjects with severe initial neck pain (OR 4.8;
      95% CI 2.9-7.8; OR 6.6; 95% CI 2.6-17.0). Associations seem to be established
      early, and then to be relatively constant over time.

PMID- 16806709
TI  - Clonidine maintains intrathecal self-administration in rats following spinal
      nerve ligation.
AB  - Clonidine is approved for spinal administration against neuropathic pain, and
      reverses both spontaneous and elicited pain in humans following spinal
      administration. Rodent studies that seek to model pharmacology in pain states
      have historically relied on reflexive withdrawal from noxious stimuli as the
      primary endpoint. Drug self-administration studies have face validity in the drug
      abuse field for modeling drug abuse in humans, however, this methodology has not
      been applied to address issues related to drug seeking behaviors that may be
      relevant for other human populations, such as patients with neuropathic pain.
      Rats without spinal nerve ligation (SNL) failed to acquire intrathecal clonidine
      self-administration over 10 days of access. Rats were found to self-administer
      intrathecal infusions of clonidine following SNL in a stable and dose-responsive
      manner, however, and clonidine was self-administered throughout the day with 66%
      of total drug intake occurring during the dark cycle. Substitution of clonidine
      with saline or with clonidine and the alpha2-adrenoceptor antagonist idazoxan
      resulted in extinction of responding in SNL animals. Food reinforcement was
      initially decreased in SNL rats self-administering clonidine compared to normal
      animals, however, tolerance developed to this effect of clonidine in SNL rats
      after 5 days. These data demonstrate that drug self-administration can be applied
      to questions other than drug abuse, and provides an additional measure for
      development of novel therapeutic strategies for chronic pain treatment.

PMID- 16806710
TI  - The effect of 300 mW, 830 nm laser on chronic neck pain: a double-blind,
      randomized, placebo-controlled study.
AB  - A randomized, double-blind, placebo-controlled study of low-level laser therapy
      (LLLT) in 90 subjects with chronic neck pain was conducted with the aim of
      determining the efficacy of 300 mW, 830 nm laser in the management of chronic
      neck pain. Subjects were randomized to receive a course of 14 treatments over 7
      weeks with either active or sham laser to tender areas in the neck. The primary
      outcome measure was change in a 10 cm Visual Analogue Scale (VAS) for pain.
      Secondary outcome measures included Short-Form 36 Quality-of-Life questionnaire
      (SF-36), Northwick Park Neck Pain Questionnaire (NPNQ), Neck Pain and Disability
      Scale (NPAD), the McGill Pain Questionnaire (MPQ) and Self-Assessed Improvement
      (SAI) in pain measured by VAS. Measurements were taken at baseline, at the end of
      7 weeks' treatment and 12 weeks from baseline. The mean VAS pain scores improved
      by 2.7 in the treated group and worsened by 0.3 in the control group (difference
      3.0, 95% CI 3.8-2.1). Significant improvements were seen in the active group
      compared to placebo for SF-36-Physical Score (SF36 PCS), NPNQ, NPAD, MPQVAS and
      SAI. The results of the SF-36 - Mental Score (SF36 MCS) and other MPQ component
      scores (afferent and sensory) did not differ significantly between the two
      groups. Low-level laser therapy (LLLT), at the parameters used in this study, was
      efficacious in providing pain relief for patients with chronic neck pain over a
      period of 3 months.

PMID- 16806711
TI  - Evaluation of the ELISA test for the antibody detection in cattle naturally and
      experimentally infected with Cysticerccus bovis.
AB  - The ELISA test was evaluated for the diagnosis of bovine cysticercosis using
      heterologous antigens from the larvae of T. solium and T. crassiceps, by using
      different types of positive and negative control sera, to allow a broader
      analysis of the results. The ELISA test showed low sensitivity under natural
      conditions of bovine cysticercosis manifestation, but high rates (up to 90%)
      under experimental conditions. The high specificity of the test (81-100%) made
      evident its capacity to differentiate cysticercosis from other bovine diseases.
      No difference in performance was found among the antigens studied. It was
      concluded that the ELISA test has deficiencies in detecting anti-cysticercosis
      antibodies of animals at slaughterhouse. However, it can be useful in detecting
      experimentally infected animals and differentiating cysticercosis from other
      bovine diseases.

PMID- 16806712
TI  - World association for the advancement of veterinary parasitology (WAAVP): second
      edition of guidelines for evaluating the efficacy of anthelmintics in swine.
AB  - Guidelines are provided for evaluating the efficacy of anthelmintics in swine
      which, in conjunction with other sets of guidance such as those of the
      International Cooperation on Harmonization of Technical Requirements for
      Registration of Veterinary Medicinal Products (VICH GL7 and VICH GL16), should
      encourage the adoption of uniform registration requirements globally. Testing of
      efficacy should be carried out according to the principles of "Good Clinical
      Practice" (VICH GL9, 2000). Data obtained according to these guidelines should be
      internationally acceptable for the registration of anthelmintics for swine.
      Further, the use of the guidelines should expedite development, government
      review, and approval of anthelmintics for swine, as well as contribute towards
      reducing costs and the number of experimental animals used for drug testing.

PMID- 16806713
TI  - Capillary and venous Babesia canis rossi parasitaemias and their association with
      outcome of infection and circulatory compromise.
AB  - This observational study of 100 dogs naturally infected with Babesia canis rossi
      determined whether severity of parasitaemia was associated with outcome of
      infection and documented the relative distribution of parasitised red blood cells
      (pRBC) in capillary and venous circulation. The association between increased
      parasitaemias and outcome with a clinically compromised circulation was also
      investigated. Outcome was defined as either hospitalisation with death, or
      hospitalisation with eventual recovery or treatment as an outpatient. Dogs were
      enrolled if large babesias were found on stained thin capillary blood smears made
      from an ear prick. Thin venous smears were prepared from jugular or cephalic
      blood. Parasitaemias were manually counted and expressed as the percent pRBC. Ten
      dogs died, 50 recovered after hospitalisation and 40 were treated as outpatients.
      Venous sampling site did not affect venous parasitaemia (P=0.6). Both capillary
      and venous parasitaemias of dogs that died were significantly higher than those
      of dogs that recovered after hospitalisation (P=0.002) and dogs that were treated
      as outpatients (P<0.0001). When assessing the whole group, capillary parasitaemia
      (median 0.61%, range <0.05-71.6%, interquartile range (IQR) 0.22-3.75%) was
      significantly higher than venous parasitaemia (median 0.14%, range 0-30.6%, IQR
      0.046-0.52%) with P<0.0001. The 21 dogs with a clinically compromised circulation
      were more likely to die (P<0.0001) and had significantly higher capillary (median
      5.98%, range 0.09-71.6%, IQR 2.44-19.41%) and venous (median 2.81%, range <0.05
      30.6%, IQR 0.17-9.03%) parasitaemias than the 79 dogs with a clinically normal
      circulation (capillary median parasitaemia 0.38%, range <0.05-12.87%, IQR 0.16
      1.42%; venous median parasitaemia 0.096%, range 0-6.13%, IQR <0.05-0.33%;
      P<0.0001). This study shows that high parasitaemia is significantly associated
      with death in B c rossi infected dogs. The previous clinical suspicion that
      capillary parasitaemias are usually higher than venous parasitaemias is
      confirmed. Thus capillary samples are the most appropriate diagnostic samples.
      Prior observations that a clinically compromised circulation is associated with
      death are confirmed. Despite the highly significant association between
      compromised circulation and higher parasitaemia, it is thought unlikely that
      parasite burden is the sole trigger for circulatory collapse.

PMID- 16806714
TI  - Analysis of neutral glycosphingolipids from Trypanosoma brucei.
AB  - Neutral glycosphingolipids (GSLs) were isolated from Trypanosoma brucei and
      analyzed by thin-layer chromatography (TLC), TLC/secondary ion mass spectrometry
      (TLC/SIMS), and liposome immune lysis assay (LILA). Three species of neutral
      GSLs, designated as N-1, -2, and -3 were separated on TLC. N-1 GSL migrated very
      close to glucosylceramide (GlcCer) and N-2 GSL showed the same mobility as
      lactosylceramide (LacCer). On the other hand, the mobility of N-3 GSL on the TLC
      plate was slower than globotetraosylceramide (Gb4). In order to characterize the
      molecular species of neutral GSLs from T. brucei, N-1, -2 and -3 GSLs were
      analyzed by TLC/SIMS. The TLC/SIMS analysis of N-1 of the parasites revealed a
      series of (M-H)- ions from m/z 698 to 825 representing the molecular mass range
      of ceramide monohexoside (CMH) (GlcCer or galactosylceramide). On the other hand,
      the TLC/SIMS spectra of N-2 GSL revealed a series of (M-H)- ions from m/z 944-987
      indicating the molecular mass range of LacCer. In the TLC/SIMS analysis of N-3
      GSL, however, the characteristic molecular ions that can elucidate the structure
      of N-3 GSL were not obtained. In order to confirm the results obtained from
      TLC/SIMS, N-1, -2, and -3, GSLs were tested by LILA with specific antibodies
      against GlcCer, LacCer, and Gb4, respectively. N-1 GSL had reactivity to anti
      GlcCer antibody and N-2 GSL reacted with the antibody against LacCer. However, N
      3 GSL was not recognized by anti-Gb4 antibody. Using anti-GlcCer and anti-LacCer
      antibodies, furthermore, we studied the expression of GlcCer and LacCer in T.
      brucei parasites. Both GlcCer and LacCer were detected on the cell surface of T.
      brucei.

PMID- 16806715
TI  - Immunocytochemical localization of scorpion digestive lipase.
AB  - The scorpion hepatopancreas consists of digestive diverticula and interstitial
      tissue. A digestive diverticulum is composed of two differentiated cell types:
      the secretory zymogene-like cells and the digestive cells which are the most
      abundant. The scorpion digestive lipase (SDL) has been previously purified from
      scorpion hepatopancreas, but its cellular localization has not yet been
      established. Polyclonal antibodies specific to SDL were prepared and used in
      immunofluorescence and immunogold techniques to determine the cellular location
      of SDL. Our results clearly established that SDL was detected intracellularly in
      specific vesicles tentatively named (SDL+) granules of the digestive cells. No
      immunolabelling was observed in secretory zymogene-like cells. This
      immunocytolocalization indicates that lipid digestion might occur in specific
      granules inside the digestive cells, as suggested by previous studies on the
      scorpion digestive process.

PMID- 16806716
TI  - Sialilated beta1,6 branched N-oligosaccharides modulate adhesion, chemotaxis and
      motility of melanoma cells: Effect on invasion and spontaneous metastasis
      properties.
AB  - B16BL6 cells, selected specifically for invasive characteristics from B16F10
      mouse melanoma cells, displayed greater ability to metastasize to lungs and
      produced larger colonies than the parent cells, when injected intravenously. When
      the two cell lines were compared for surface beta1,6-branched N-oligosaccharides
      by flow cytometry using Leuco-Phyto-Heam-Agglutinin, B16BL6 were found to express
      significantly higher levels. Inhibition of the oligosaccharide expression, by
      treatment of the cells with swainsonine or antisense-N-acetyl glucosaminyl
      transferase-V, significantly reduced metastasis and invasion (>50%). Further,
      inhibition of oligosaccharides on the molecules like beta1 integrin (one of the
      major carriers) caused 30-45% reduction in their adherence to extra-cellular
      matrix components especially collagen IV and laminin, and chemotaxis towards
      fibronectin and matrigel. The inhibition also decreased haptotaxis by
      approximately 50% to fibronectin but surprisingly was enhanced towards laminin by
      approximately 75%. The cells on which the expression of these oligosaccharides
      was inhibited failed to exhibit the characteristic spontaneous metastasis and
      adhesion properties of B16BL6 cells. In none of the cases, however, the secretion
      of matrix-metallo-proteases correlated with oligosaccharide expression.
      Sialylation of surface oligosaccharides was found to be accompanied by even
      higher motility and adherence to the substrates. These results strongly support
      an important role of cell surface beta1,6-linked N-oligosaccharides, especially
      the sialylated derivatives, in the processes that influence invasion and
      metastasis.

PMID- 16806717
TI  - Mechanisms of modulation of pregnanolone on glycinergic response in cultured
      spinal dorsal horn neurons of rat.
AB  - The glycine receptors and neurosteroids in spinal cord are both implicated in
      nociceptive signal processing. However, the modulatory effects of neurosteroid
      pregnanolone (5beta-pregnan-3alpha-ol-20-one) on native glycine receptors remain
      unclear. In the present study, we examined the effects of pregnanolone and its
      three isomers on glycine receptors by using whole-cell patch-clamp technique. Our
      results showed that pregnanolone reversibly inhibited the amplitude of glycine
      induced current mediated by native glycine receptors and recombinant alpha1-,
      alpha2-, alpha3- and alpha1beta-glycine receptors. In cultured spinal dorsal horn
      neurons of rats, pregnanolone inhibited the glycine-induced current in dose
      dependent manner, with an antagonist concentration inducing half-maximal response
      of 1.0+/-0.3 microM. The inhibitory effect of pregnanolone on glycine-induced
      current was voltage-independent and pregnanolone shifted the concentration
      response curve for glycine-induced current rightward in a parallel manner without
      altering the maximal value and Hill coefficient. The isomer of pregnanolone,
      allopregnanolone (5alpha-pregnan-3alpha-ol-20-one) slightly enhanced glycine
      induced current, whereas iso-pregnanolone (5beta-pregnan-3beta-ol-20-one) and iso
      allopregnanolone (5alpha-pregnan-3beta-ol-20-one) did not affect the glycine
      induced current significantly in cultured spinal dorsal horn neurons. Thus, our
      results suggest that the inhibitory effect of pregnanolone on glycine-induced
      current is of a competitive type and depends on the stereo structure of
      pregnanolone. Furthermore, pregnanolone decreased the amplitude and frequency of
      the glycinergic miniature inhibitory postsynaptic currents. Through modulating
      the glycinergic inhibitory neurotransmission, pregnanolone may affect the
      nociceptive sensory processing under physiological and pathological conditions.

PMID- 16806718
TI  - Normal aging of offspring mice of mothers with induced inflammation during
      pregnancy.
AB  - Intrauterine inflammation is a major risk for offspring neurodevelopmental brain
      damage and may result in cognitive limitations and poor cognitive and perceptual
      outcomes. In the present study we tested the possibility that prenatal exposure
      to a high level of inflammatory factors may increase the risk for
      neurodegeneration in aging. The effect of systemic maternal inflammation (MI),
      induced by lipopolysaccharide (LPS) on offspring brain aging, was examined in 8
      month old (adult) and 20 month old (aged) offspring mice. A significant effect of
      age was found in the distance and velocity of exploration in the open field in
      both groups. In addition, MI aged offspring covered longer distances and enter
      frequently to the center of the field compared with the aged control group.
      Although only little difference was found in the aged MI offspring compared with
      the control offspring, the overall profile of behavior of these mice differs from
      that of the control group, as detected by clustering analysis. The expression of
      the death-associated protein FAS-ligand and the amount of apoptotic cell death
      were examined in the brains of aged offspring. Similar levels of FAS-ligand
      expression and parallel density of apoptotic cells were detected in the brains of
      aged mice of control and MI groups. Altogether, moderate systemic MI was not
      found to increase the risk for cell death in the aged offspring; limited effect
      was found in mice profile of behavior.

PMID- 16806719
TI  - Compartmental distribution of hyperpolarization-activated cyclic-nucleotide-gated
      channel 2 and hyperpolarization-activated cyclic-nucleotide-gated channel 4 in
      thalamic reticular and thalamocortical relay neurons.
AB  - Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels conduct a
      monovalent cationic current, I(h), which contributes to the electrophysiological
      properties of neurons and regulates thalamic oscillations in circuits containing
      the glutamatergic ventrobasal complex (VB) and GABAergic reticular thalamic
      nucleus (RTN). Four distinct HCN channel isoforms (HCN1-4) have been identified,
      and mRNAs and proteins for HCN channels have been detected in the RTN and VB,
      with HCN2 and HCN4 being the predominant isoforms. RTN and VB neurons have
      distinct electrophysiological properties, and those differences may reflect
      variable compartmental distribution of HCN channels. Whole cell patch clamp
      recordings from thalamic neurons in brain slices obtained from C57/Bl6 mice
      demonstrate that I(h) is much smaller in RTN than in VB neurons although the time
      constants for I(h) current activation are very similar. To study the
      compartmental distribution of the underlying channels, we performed qualitative
      and quantitative examination of HCN2 and HCN4 expression using fluorescent
      immunohistochemistry and confocal microscopy. HCN2-immunoreactivity (IR) on the
      somata of RTN neurons was approximately 10-fold less than that seen in VB neurons
      while HCN4-IR was detected on the somata of RTN and VB neurons to an equal
      degree. HCN2-IR in RTN and VB did not overlap with synaptophysin-IR, but strongly
      colocalized with cortactin-IR, indicating that HCN2 was not present in axon
      terminals but was present in dendritic spines. Although HCN2-IR in spines was
      more pronounced in VB than in RTN, the ratio of spinous to somatic expression in
      RTN was dramatically higher than that in VB, strongly suggesting that HCN2-IR in
      RTN is principally located in sites distal to the soma. In contrast, HCN4-IR did
      not colocalize with either synaptophysin or cortactin. The colocalization of HCN2
      IR with HCN4-IR was greater in VB than in RTN. The results suggest that the
      distinct compartmental distribution of HCN2 channels in RTN and VB neurons
      contributes to the profound differences in the I(h)-dependent properties of these
      cells.

PMID- 16806720
TI  - Limited brain diffusion of the glucocorticoid receptor agonist RU28362 following
      i.c.v. administration: implications for i.c.v. drug delivery and glucocorticoid
      negative feedback in the hypothalamic-pituitary-adrenal axis.
AB  - The experiments described herein present a method for tracking diffusion of the
      glucocorticoid receptor agonist RU28362 in brain following i.c.v. drug
      administration. A useful property of glucocorticoid receptor is that it is
      primarily cytoplasmic when unbound and rapidly translocates to the nucleus when
      bound by ligand. Thus, removal of endogenous glucocorticoids by adrenalectomy
      allows us to identify brain regions with activated glucocorticoid receptor after
      i.c.v. glucocorticoid receptor agonist treatment by examining the presence or
      absence of nuclear glucocorticoid receptor immunostaining. We have previously
      demonstrated that an i.p. injection of 150 microg/kg RU28362 1 h prior to
      restraint stress is sufficient to suppress stress-induced hypothalamic-pituitary
      adrenal axis hormone secretion [Ginsberg AB, Campeau S, Day HE, Spencer RL (2003)
      Acute glucocorticoid pretreatment suppresses stress-induced hypothalamic
      pituitary-adrenal axis hormone secretion and expression of corticotropin
      releasing hormone hnRNA but does not affect c-fos mRNA or fos protein expression
      in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol 15:1075
      1083]. We report here, however, that in rats i.c.v. treatment with a high-dose of
      RU28362 (1 microg) 1 h prior to stressor onset does not suppress stress-induced
      hypothalamic-pituitary-adrenal axis activity. We then performed a series of
      experiments to examine the possible differences in glucocorticoid receptor
      activation patterns in brain and pituitary after i.c.v. or i.p. treatment with
      RU28362. In a dose-response study we found that 1 h after i.c.v. injection of
      RU28362 (0.001, 0.1 and 1.0 microg) glucocorticoid receptor nuclear
      immunoreactivity was only evident in brain tissue immediately adjacent to the
      lateral or third ventricle, including the medial but not more lateral portion of
      the medial parvocellular paraventricular nucleus of the hypothalamus. In
      contrast, i.p. injection of RU28362 produced a uniform predominantly nuclear
      glucocorticoid receptor immunostaining pattern throughout all brain tissue.
      I.c.v. injection of the endogenous glucocorticoid receptor agonist,
      corticosterone (1 microg) also had limited diffusion into brain tissue. Time
      course studies indicated that there was not a greater extent of nuclear
      glucocorticoid receptor immunostaining present in brain after shorter (10 or 30
      min) or longer (2 or 3 h) intervals of time after i.c.v. RU28362 injection.
      Importantly, time-course studies found that i.c.v. RU28362 produced significant
      increases in nuclear glucocorticoid receptor immunostaining in the anterior
      pituitary that were evident within 10 min after injection and maximal after 1 h.
      These studies support an extensive literature indicating that drugs have very
      limited ability to diffuse out of the ventricles into brain tissue after i.c.v.
      injection, while at the same time reaching peripheral tissue sites. In addition,
      these studies indicate that significant occupancy of some glucocorticoid receptor
      within the paraventricular nucleus of the hypothalamus and pituitary is not
      necessarily sufficient to suppress stress-induced hypothalamic-pituitary-adrenal
      axis activity.

PMID- 16806721
TI  - Different receptors mediate the electrophysiological and growth cone responses of
      an identified neuron to applied dopamine.
AB  - Neurotransmitters are among the many cues that may guide developing axons toward
      appropriate targets in the developing nervous system. We have previously shown in
      the mollusk Lymnaea stagnalis that dopamine, released from an identified pre
      synaptic cell, differentially affects growth cone behavior of its target and non
      target cells in vitro. Here, we describe a group of non-target cells that also
      produce an inhibitory electrophysiological response to applied dopamine. We first
      determined, using pharmacological blockers, which receptors mediate this
      physiological response. We demonstrated that the dopaminergic
      electrophysiological responses of non-target cells were sensitive to a D2
      receptor antagonist, as are known target cell responses. However, the non-target
      cell receptors were linked to different G-proteins and intracellular signaling
      pathways than the target cell receptors. Despite the presence of a D2-like
      receptor at the soma, the growth cone collapse of these non-target cells was
      mediated by D1-like receptors. This study shows that different dopamine receptor
      sub-types mediated the inhibitory physiological and growth cone responses of an
      identified cell type. We therefore not only provide further evidence that D2- and
      D1-like receptors can be present on the same neuron in invertebrates, but also
      show that these receptors are likely involved in very different cellular
      functions.

PMID- 16806722
TI  - The role of adolescent social disinhibition expectancies in moderating the
      relationship between psychological distress and alcohol use and misuse.
AB  - We examined the effects of adolescent social disinhibition expectancies and adult
      psychological distress on alcohol use and misuse in adulthood, using the 1970
      British Cohort Study data. Multivariate imputation by chained equations filled in
      incomplete cases for 7023 men and 6896 women. A propensity to heavy alcohol use
      and misuse was predicted by social expectations of the releasing effects of
      alcohol acquired in adolescence (adolescent social disinhibition expectancies).
      Psychological distress at age 30 increased the likelihood of very heavy alcohol
      use in men and misuse of alcohol in men and women. An absence of adolescent
      social disinhibition expectancies protects adults from drinking alcohol.
      Moreover, among men without these expectancies, psychological distress did not
      predict heavy alcohol use, whereas this association was present among men with
      expectations of alcohol. Policies that aim to manage adult alcohol use should be
      initiated in adolescence. Reduction of psychological distress will prevent both
      men and women from misusing alcohol.

PMID- 16806723
TI  - Target-derived neurotrophins may influence the survival of adult retinal ganglion
      cells when local neurotrophic support is disrupted: Implications for glaucoma.
AB  - Following target innervation, developing and neonatal retinal ganglion cells
      (RGCs) depend on neurotrophic factors from their target tissue for survival. This
      dependence is reduced for adult RGCs which rely primarily on trophic support from
      their local environment; however, some findings indicate that target tissue may
      play a role in the long-term survival of RGCs. We propose that a deficiency in
      neurotrophic factors from the target tissue may influence the survival of RGCs
      when local neurotrophic support is disrupted. Furthermore, we propose that this
      hypothesis may explain, at least in part, the progressive loss of RGCs in optic
      neuropathies such as glaucoma. Neurotrophic factors are present in the adult
      superior colliculus and they are trafficked to the retina; however, removal or
      lesioning of the adult target tissue results in little or no RGC loss for up to
      several months. In vitro, adult RGCs will survive when maintained by co-culturing
      these neurons with their target tissue. As well, the timing and pattern of adult
      RGC loss is consistent with that seen in glaucoma and in reports of delayed RGC
      loss following target-removal. Our hypothesis can be tested by selectively
      disrupting local neurotrophic support and evaluating RGC survival when target
      derived neurotrophic support is maintained and when it is disrupted.
      Specifically, intravitreal injection of blocking antibodies could be used to
      disrupt local neurotrophic signaling, while aspiration of the superior colliculus
      will eliminate retrograde transport from the primary target tissue in rodents.
      The results of these experiments would provide valuable information concerning
      the influence of target-derived neurotrophic support when local neurotrophin
      signaling is disrupted. Specifically, this research could verify whether
      deficiencies in target-derived neurotrophic support play a role in RGC loss
      during glaucoma. A further understanding of this mechanism may lead to the
      development of effective neuroprotective strategies for treating glaucoma.

PMID- 16806724
TI  - The timing is right: Evolution of AIDS-causing HIV strains is consistent with
      history of chloroquine use.

PMID- 16806725
TI  - Insular Alzheimer's disease pathology as a cause of "age-related" autonomic
      dysfunction and mortality in the non-demented elderly.
AB  - Only a few brain structures have been implicated in the autonomic control of
      blood pressure and heart rate. Among them are heteromodal association areas in
      the cortex, especially the insular cortex. Ischemic insular lesions have been
      associated with both cardiac arrhythmias and mortality. However, stroke may not
      be the only insular pathology with the potential to disrupt autonomic function.
      Alzheimer's disease (AD) is associated with both insular pathology and autonomic
      dysfunction. Alzheimer's dementia is merely the final stage of a pathological
      process that spans decades. Recent studies have demonstrated a hierarchichal
      sequence of AD pathology that includes the insular cortex. This may explain why
      AD has effects on BP and central autonomic cardio-regulatory functions. However,
      AD reaches the insular cortex at a "preclinical" stage in its development (i.e.,
      before "dementia" can be diagnosed). Thus, AD pathology should also be considered
      as a possible explanation for autonomic morbidity and mortality in non-demented
      elderly persons. We hypothesize that autonomic dyscontrol, commonly seen in non
      demented well elderly persons without significant cardiovascular disease (CVD),
      reflects subclinical stages of AD pathology affecting the insular cortex. If
      true, then preclinical AD pathology should be considered as a possible
      explanation for arrhythmia/fall related morbidity and mortality in non-demented
      elderly persons.

PMID- 16806726
TI  - A possible hypoxia-induced endothelial proliferation in the pathogenesis of
      epithelioid hemangioma.
AB  - Epithelioid hemangioma is an uncommon benign vascular lesion with distinct
      clinicopathological characteristics. Histologically, this entity mainly composed
      of well-formed but often immature vessels lined by epithelioid endothelial cells
      with prominent chronic inflammatory component. There is considerable controversy
      whether epithelioid hemangioma is a reactive lesion or a true neoplasm. We
      postulated that the local hypoxia may play a role in the pathogenesis of this
      vascular tumor. This local hypoxic condition may caused by many incidences such
      as congenital vascular malformation or trauma. The hypoxia will lead to the
      proliferation of endothelial cells and the formation of this vascular tumor,
      which may lead by putative stimulators VEGF and HIF-1. Hypoxia may also promote
      endothelial cell proliferation through the renin-angiotensin-aldosterone system.
      Additionally, the inflammatory cells including eosinophils and mast cells may
      contribute to the endothelial cell proliferation in EH. Further study
      investigating the associated factors of hypoxia may lead to new, potentially
      important insights into epithelioid hemangioma, and might also contribute to
      novel strategies for the management of this entity.

PMID- 16806727
TI  - Pro-inflammatory cytokines may induce late preconditioning in unstable angina
      patients.
AB  - Late preconditioning can be induced by a wide variety of stimulus, including non
      pharmacological and pharmacological. Thus, late preconditioning is a universal
      response of the heart to stress and it requires the simultaneous activation of
      multiple stress-responsive genes. Recently, compelling evidence has evolved that
      the up-regulation of pro-inflammatory cytokines plays an important role in
      induction of the late phase of ischemic preconditioning in rodent models.
      However, the role of cytokines in induction of late preconditioning in humans has
      not been explored. Patients with unstable coronary syndromes have a systemic
      inflammatory responses with increase of the pro-inflammatory cytokines, such as
      TNFalpha, IL-6. And some researchers find the patients undergoing CABG with
      unstable angina have a better cardioprotective effect caused by late
      preconditioning characterized by the activated NF-kappaB and synthesized effector
      proteins (HSP72 and eNOS). Therefore, we hypothesize that pro-inflammatory
      cytokines may induce late preconditioning in unstable angina patients directly or
      through remote preconditioning. It is difficult to test our hypotheses in vivo,
      but in vitro, human tissue culture with isolated atrial myocardium could be
      tested. If the hypotheses is true, the biological complication is immense. A new
      physiological function of pro-inflammatory cytokines is found, that is, inducing
      endogenous cytoprotection. From the clinical point of view, administering the
      appropriate pro-inflammatory cytokines will be beneficial to patients before
      cardiac surgery.

PMID- 16806728
TI  - An expanded microarray platform for diagnosis of nonbacterial sepsis: potential
      usefulness for immunosuppressed patients.

PMID- 16806729
TI  - Inhibition of SHH signaling pathway: molecular treatment strategy of odontogenic
      keratocyst.
AB  - Odontogenic keratocyst (OKC) is a relatively common cystic lesion occurred in the
      tooth-bearing areas of the jaws. This entity is thought to arise from the dental
      lamina or its remnant with significant growth capacity and recurrence potential.
      The Sonic hedgehog (SHH) signaling pathway plays a critical role in tooth
      development. Patched (PTCH) combines with Smoothened (SMO) to form a receptor
      complex for SHH ligand. Mutations in the PTCH resulting in aberrant activation of
      SHH signaling pathway were identified as the underlying genetic event of both
      sporadic and syndrome-related OKCs. We postulate that any strategy to develop
      antagonists of active receptor, transcriptional factors of SHH signaling pathway
      will be an effective treatment for OKC. These strategies include reintroducing a
      wild-type form of PTCH, inhibition of the SMO molecule by synthetic small
      antagonists and suppression of the downstream transcription factors of the SHH
      signaling pathway. It seems that inhibition of SMO by intracystic injection of
      antagonist protein of SMO is the most potential treatment choice.

PMID- 16806730
TI  - Sympathetic nervous system plays an important role in the relationship between
      immune mediated diseases.
AB  - T helper (Th) lymphocytes have been classified into distinct subsets, Th1 and Th2
      on the basis of the cytokines they produce. According to the cross-regulatory
      properties of Th1 and Th2 cells, one would assume that to be affected by a Th1
      type disease increases susceptibility to a Th1 type disease and inhibits a Th2
      type disease and vice versa about being affected by a Th2 type disease. However,
      the pattern of related diseases does not necessarily follow the conventional
      pattern of inhibitory effects of Th1 and Th2 immune responses on each other. For
      example, Mycobacteria including BCG, that induce Th1 immune responses; can
      modulate some Th1 type autoimmune diseases including MS, experimental autoimmune
      encephalomyelitis (EAE; an animal model for Multiple Sclerosis) and insulin
      dependent diabetes mellitus (IDDM) thereby leading to an alleviation of their
      symptoms. Also BCG precipitates a syndrome similar to systemic lupus
      erythematosus (SLE), a Th2 type disease; in NOD mice. The coexistence of the
      major Th2-mediated atopic diseases such as asthma, eczema and allergic rhinitis
      with the Th1-mediated autoimmune conditions including; coeliac disease (CD),
      IDDM, rheumatoid arthritis (RA) and psoriasis is another example that is in
      apparent disagreement with counter-regulatory effects of Th1/Th2 phenotypes.
      HYPOTHESIS: SNS can be stimulated by pro-inflammatory cytokines, production of
      which is induced by mycobacteria including BCG. Although these cytokines can
      inhibit SNS activity in the site of inflammation and secondary lymphoid organs,
      they increase sympathetic tone in other places. Increased sympathetic tone can
      induce an anti-inflammatory and Th2 type milieu. This milieu can inhibit MS and
      IDDM and provide a susceptible environment for starting of SLE. Atopic diseases
      are Th2 type immune mediated diseases; therefore, they increase the production of
      Th2 type cytokine and decrease production of pro-inflammatory cytokines in the
      site of allergic reaction and also in secondary lymphoid organs. Therefore,
      atopic diseases decrease sympathetic tone in all tissues except in the sites of
      allergic reaction and secondary lymphoid organs. Decreased sympathetic tone
      results in a pro-inflammatory milieu and in such an environment, Th1 type
      autoimmune diseases can affect tissues.

PMID- 16806731
TI  - The Unitarian Hypothesis for the aetiology of diabetes mellitus.
AB  - Over the years, several clinical syndromes have been described in diabetes
      mellitus. Although world opinion has settled somewhat on the main two types, the
      debate continues as to how the 'formes frustes' syndromes fit in and what if any
      implications there are for the accepted aetiology of the disease. Type 1, insulin
      dependent diabetes mellitus, results from pancreatic inadequacy as a result of a
      variety of insults such as autoimmune attack, toxic damage, etc. Insulin
      administration is at the core of the therapeutic approach. Type 2, non insulin
      dependent diabetes mellitus, results from reduced responsiveness of the target
      tissues to insulin and as such, an insulin resistance syndrome is described.
      Lifestyle adjustment and oral hypoglycaemic agents are the mainstay of therapy.
      Over the years, however, insulin insufficiency will develop in most cases and
      insulin therapy required in order to achieve normoglycaemia. The aetiology of
      these main two types has been maintained to be distinct from each other and as
      such types 1 and 2 are described as two separate developmental conditions.
      Furthermore, the variant patterns, such as malnutrition related, drug induced,
      intermittent or phasic insulin requiring, gestational, temporary, stress related,
      etc., all present a challenge as to how they fit in aetiologically. The Unitarian
      Hypothesis, by presenting this overall cascade of biochemical and physiological
      interactions, brings a logic which embraces the points of entry of a variety of
      insults, all of which can lead to the clinical picture of hyperglycaemia and its
      attendant adverse outcomes. The hypothesis buttresses the belief that nature -
      the genetic predisposition which directs potential antibody development; and
      nurture - the environmental influences such as nutritional status (over- or under
      ), infective and toxic attack, can aggravate or initiate aspects of the cascade
      of reactions leading to hyperglycaemia. The causative agents functioning
      internally within the cascade are imputed to be free radicals, oxidizing
      molecular species and antibodies and the corollary to this overview concept would
      be that a situation that minimizes the genesis and accumulation of these three
      agents would minimize the development of diabetes mellitus. Currently the debate
      is rife about the use of free radical scavengers and antioxidants in the
      treatment and prevention of diabetes mellitus. The verdict is still out on this
      approach. Our research on rootcrops such as yams and cassava, staple foods in
      tropical countries, indicates the presence of cyanoglycosides such as linamarin,
      which on digestion yields cyanide radicals. These radicals are pancreatotoxic
      especially in the undernourished state. Dog models however, have shown that free
      radical scavengers such as riboflavin, Vitamin B(2), is protective against this
      toxic damage. Further, scientific investigations have clearly demonstrated the
      role of antibody attack and have been able to ward off the appearance of type 1
      diabetes mellitus in susceptible individuals, by the early use of
      immunosuppressive therapy such as cyclosporin. Thus the Unitarian Hypothesis
      demonstrates how all types of clinical syndromes being described in diabetes
      mellitus are not necessarily variants of a specific illness but rather
      manifestations of a central process of membrane damage-->antibody response-
      >insulin inadequacy (quantitatively or qualitatively); and the future
      intervention in containing this disease may well lie in focusing on preservation
      of the integrity of the body's cell membranes.

PMID- 16806732
TI  - Bird flu, influenza and 1918: the case for mutant Avian tuberculosis.
AB  - Influenza is Italian for "influence", Latin: influentia. It used to be thought
      that the disease was caused by a bad influence from the heavens. Influenza was
      called a virus long, long before it was proven to be one. In 2005, an article in
      the New England Journal of Medicine estimated that a recurrence of the 1918
      influenza epidemic could kill between 180 million and 360 million people
      worldwide. A large part of the current bird-flu hysteria is fostered by a
      distrust among the lay and scientific community regarding the actual state of our
      knowledge regarding the bird flu or H5N1 and the killer "Influenza" Pandemic of
      1918 that it is compared to. And this distrust is not completely unfounded.
      Traditionally, "flu" does not kill. Experts, including Peter Palese of the Mount
      School of Medicine in Manhattan, remind us that even in 1992, millions in China
      already had antibodies to H5N1, meaning that they had contracted it and that
      their immune system had little trouble fending it off. Dr. Andrew Noymer and
      Michel Garenne, UC Berkely demographers, reported in 2000 convincing statistics
      showing that undetected tuberculosis may have been the real killer in the 1918
      flu epidemic. Aware of recent attempts to isolate the "Influenza virus" on human
      cadavers and their specimens, Noymer and Garenne summed that: "Frustratingly,
      these findings have not answered the question why the 1918 virus was so virulent,
      nor do they offer an explanation for the unusual age profile of deaths". Bird flu
      would certainly be diagnosed in the hospital today as Acute Respiratory Distress
      Syndrome (ARDS). Roger and others favor suspecting tuberculosis in all cases of
      acute respiratory failure of unknown origin. By 1918, it could be said, in so far
      as tuberculosis was concerned, that the world was a supersaturated sponge ready
      to ignite and that among its most vulnerable parts was the very Midwest where the
      1918 unknown pandemic began. It is theorized that the lethal pig epidemic that
      began in Kansas just prior to the first human outbreaks was a disease of avian
      and human tuberculosis genetically combined through mycobacteriophage
      interchange, with the pig, susceptible to both, as its involuntary living culture
      medium. What are the implications of mistaking a virus such as Influenza A for
      what mycobacterial disease is actually causing? They would be disastrous, with
      useless treatment and preventative stockpiles. The obvious need for further
      investigation is presently imminent and pressing.

PMID- 16806733
TI  - Increased cell division contributes to carcinogenesis by both gene mutation and
      aneuploidy.

PMID- 16806734
TI  - A hypothesis: Sunspot cycles may detect pandemic influenza A in 1700-2000 A.D.
AB  - BACKGROUND: Influenza pandemics in this century (1946-1947, 1957 and 1968) have
      fascinated some people for the idea of 11-year pattern pandemic cycles. In solar
      physics, it is well known that sunspot cycles also have regular periods of around
      11 years. This study therefore aims to investigate the association between
      sunspot cycles and the occurrences of pandemic influenza. The hypothesis here
      states that sunspot numbers can detect pandemic influenza A between 1700 and 2000
      A.D. PRESENTATION OF THE HYPOTHESIS: Antigenic shift of influenza occurs is a
      result of genetic reassortment between animal and human influenza A viruses. It
      is suggested the viruses spread from the migratory birds to other avian species
      such as chicken or ducks along their migratory pathways. Solar activity has an
      influence on terrestrial climate in terms of temperature, rainfall, storms and
      finally the biological systems. It was shown that the arrival dates of some
      migratory birds were delayed with increased sunspot numbers. This delay arrival
      may be associated with increased contacts with other susceptible birds in their
      migratory routes that facilitate genetic reassortment of the circulating
      influenza viruses. TEST THE HYPOTHESIS: Comprehensive reviews on both pandemics
      and possible pandemics of influenza were searched. International sunspot numbers
      were obtained from the World Data Center for Sunspot Index, Belgium and used to
      detect pandemics by binomial test. Five comprehensive reviews were found and the
      agreements on pandemics were good to excellent. Sensitivity of using Sunspot
      Number more than 50 (SSN>50) to detect pandemics increased as the levels of
      agreements increased. In stringent criteria, two pandemics might have occurred in
      the 18th century (1729-1733 and 1781-1782), two in the 19th century (1830-1833
      and 1889-1892) and three in the 20th century (1918-1920, 1957-1958 and 1968
      1969). The sensitivity of using SSN>50 to detect influenza pandemics was 85.7%
      (95%CI=59.8-100%, p=0.019). The specificity was 51.2% (95%CI=35.9-66.5%).
      IMPLICATIONS OF THE HYPOTHESIS: On top of virological and epidemiological
      surveillance, sunspot cycles may be an inexpensive and easy method to detect
      influenza pandemics. The next high risk period will be around 2008-2013 and it
      may suggest us to be more alert and be prepared in order to minimize unnecessary
      deaths as a result of influenza.

PMID- 16806735
TI  - Acquisition, extinction and temporal discrimination in human conditioned
      avoidance.
AB  - Two experiments were conducted with the aim of designing a videogame for the
      study of human conditioned avoidance. Participants had to destroy enemy
      spaceships with the goal of increasing the score in a counter. Coloured signals
      might announce the launching of a bomb that could hit participant's spaceship
      producing a 30 points decrease in participant's score. Three groups of
      participants were trained in discriminating between a warning signal (W) and a
      safety signal (S) in Experiment 1. Instrumental group could avoid the loss of
      points by hiding the spaceship before the offset of W. Participants in the Yoked
      group received the same treatment received by their instrumental partners,
      regardless of their behaviour. In the Pavlovian group, W was always followed by
      the loss of points, regardless of participant's behaviour. Discrimination between
      W and S was better in the Instrumental groups than in the Yoked and Pavlovian
      control groups. Experiment 2 found extinction of avoidance when the warning
      signal was not followed by the bomb. Temporal discrimination was found within the
      participants that received the instrumental contingency in both experiments, with
      higher avoidance response towards the end of the warning signal. Temporal
      discrimination disappeared after extinction in Experiment 2.

PMID- 16806736
TI  - Generalization of conditioned food aversions in grazing sheep and its
      implications for food categorization.
AB  - When grazing on heterogeneous pastures, herbivores may rely on food item
      generalization and categorization processes for reducing information processing
      while selecting their diet. The objective of this study was to assess the
      generalization of an aversion by grazing sheep for items differing by one or two
      criteria from an item against which they were negatively conditioned. Four items
      cultivated in pots were offered to the animals, resulting from the combination of
      an intrinsic criterion, i.e. grass species (ryegrass and fescue) and a transitory
      criterion, i.e. sward height (tall and short). We assessed the generalization
      process by comparing binary choices between the initially preferred tall ryegrass
      and the three other items, before and after animals had been partially
      conditioned against tall ryegrass. This method proved useful in assessing the
      generalization of an aversion. Sheep did not generalize their aversion on the
      basis of sward height but rather on species: they increased their preference for
      tall fescue and decreased their instantaneous preference for short ryegrass after
      having been conditioned against tall ryegrass. The generalization of an aversion
      through different states of a same species could indicate the possibility of a
      species-based categorization by grazing herbivores.

PMID- 16806737
TI  - Strategic self-regulation, decision-making and emotion processing in poly
      substance abusers in their first year of abstinence.
AB  - Individuals with substance dependence (ISD) frequently show signs of impaired
      emotion processing, self-regulation and decision-making, even after prolonged
      abstinence from drug use and partial recovery of other neuropsychological
      functions. These impairments have been associated with alterations in the
      orbitofrontal cortex (OFC) in lesion and imaging studies. The aim of this study
      was to examine the performance of a group of ISD, who had been abstinent for at
      least 4 months, on a series of emotional perception, self-regulation and decision
      making tests sensitive to OFC dysfunction. Thirty ISD (poly-substance abusers in
      their first year of abstinence) and 35 healthy comparison (HC) participants were
      in the study. We administered the Ekman Faces Test (EFT), the Revised Strategy
      Application Test (R-SAT) and the Iowa Gambling Task (IGT) to both ISD and HC.
      Results showed that the ISD presented significant deficits in the recognition of
      facial emotional expressions and decision-making as measured by the EFT and the
      IGT. The ISD also showed poorer strategy awareness, impaired self-regulation and
      higher impulsivity on the R-SAT. We found significant correlations between the
      different measures linked to OFC functioning. We did not find significant
      correlations between length of abstinence and performance on these tests. These
      results suggest that the evaluation of emotion, self-regulation and decision
      making contributes greatly to the characterization of the persistent deficits
      exhibited by ISD during prolonged abstinence.

PMID- 16806738
TI  - Prospective validation of substance abuse severity measures from administrative
      data.
AB  - BACKGROUND: Severity measures for clients in substance abuse treatment programs
      are becoming increasingly important as funders adopt payment systems linked to
      agency performance. Recently, two severity measures based on administrative data
      have been developed. This study validated these measures using prospective data.
      METHODS: Subjects were participants in the Drug Abuse Treatment Outcomes Study
      (adult or adolescent components) or the Substance Abuse and Mental Health
      Services Administration Medicaid Managed Behavioral Healthcare and Vulnerable
      Populations project (adult or adolescent chemical dependency components).
      Severity measures were calculated based on data obtained at entry into substance
      abuse treatment. The baseline severity measures were included along with age,
      gender, and race/ethnicity in logistic regression models predicting abstinence at
      follow-up for alcohol use, marijuana use, cocaine use, or heroin use. RESULTS:
      For adults, the severity measures were highly statistically significant (p<0.001)
      for all models in both data sets, indicating that adults with higher severity
      were more likely (and much more likely in many cases) to use alcohol, marijuana,
      cocaine, or heroin at the follow-up interview than were those with lower
      severity. For adolescents, the severity measure was highly statistically
      significant (p<0.001) for marijuana in both data sets and for alcohol in the
      Medicaid data set. CONCLUSIONS: Baseline severity measures were powerful
      predictors of abstinence at follow-up. These measures, derived from routinely
      available electronic records, appear to have noteworthy predictive validity. The
      severity indicators can be used for administrative purposes such as risk
      adjustment when examining treatment agency performance.

PMID- 16806739
TI  - Age-period-cohort influences on trends in past year marijuana use in the US from
      the 1984, 1990, 1995 and 2000 National Alcohol Surveys.
AB  - BACKGROUND: Previous studies have described trends in marijuana use in the US and
      examined age-period-cohort (APC) effects finding increased lifetime use among
      cohorts born after 1945. However, no studies have utilized data on current
      consumption in multiple cross-sectional surveys to estimate these factors.
      METHODS: Age-period-cohort models including demographic factors are estimated
      using logistic regressions in four US National Alcohol Surveys (NAS) conducted
      between 1984 and 2000. Trends in past year marijuana use are also evaluated.
      RESULTS: Marijuana use declined over the study period from 10% to 7.2% of the
      population. Declines were mainly seen among men, resulting in a degree of gender
      convergence, particularly for those aged 18-25. Significant effects of age,
      period and cohort were found, with steep declines in use by age from the early
      20s to the 40s. All male cohorts born after 1945 and female cohorts born between
      1945 and 1960 showed elevated prevalence compared to earlier cohorts.
      CONCLUSIONS: Trend results from the NAS differ from those in other surveys and
      indicate decreased prevalence of past year marijuana use and gender convergence.
      APC results confirm past findings of age effects and cohort differences between
      those born before and after 1945. Marijuana use presents many measurement
      difficulties and future research to understand differences across surveys is
      needed.

PMID- 16806740
TI  - Patterns of acquisitive crime during methadone maintenance treatment among
      patients eligible for heroin assisted treatment.
AB  - OBJECTIVE: To determine the patterns of acquisitive crime during methadone
      maintenance treatment among chronic, treatment-resistant heroin users eligible
      for heroin assisted treatment in the Netherlands. METHODS: We retrospectively
      assessed the type and number of illegal activities during 1 month of standard
      methadone maintenance treatment in 51 patients prior to the start of heroin
      assisted treatment. Data were collected using a semi-structured interview
      focussed on crime with special emphasis on property crime. Volume analyses
      consisted of frequencies and descriptives of mean numbers of offences per day and
      per type. RESULTS: In a Dutch population of problematic drug users eligible for
      and prior to commencing heroin assisted treatment, 70% reported criminal
      activities and 50% reported acquisitive crimes. Offending took place on 20.5 days
      per month with on average 3.1 offences a day. Acquisitive crime consisted mainly
      of shoplifting (mean 12.8 days, 2.2 times/day) and theft of bicycles (mean 5.8
      days, 2.4 times/day); theft from a vehicle and burglaries were committed less
      frequently. The majority of these patients (63%) reported to have started
      offending in order to acquire illicit drugs and alcohol. CONCLUSION: During
      methadone maintenance treatment, 50% of criminally active, problematic heroin
      users eligible for heroin assisted treatment reported acquisitive crime.
      Shoplifting, thefts and/or other property crimes were committed on average two to
      three times on a crime day. This study discusses that the detail provided by self
      reported crime data can improve cost estimates in economic evaluations of heroin
      assisted treatment.

PMID- 16806741
TI  - On the abundance, amino acid composition, and evolutionary dynamics of low
      complexity regions in proteins.
AB  - Protein sequences frequently contain regions composed of a reduced number of
      amino acids. Despite their presence in about half of all proteins and their
      unusual prevalence in the malaria parasite Plasmodium falciparum, the function
      and evolution of such low-complexity regions (LCRs) remain unclear. Here we show
      that LCR abundance and amino acid composition depend largely, but not
      exclusively, on genomic A+T content and obey power-law growth dynamics. Further,
      our results indicate that LCRs are analogous to microsatellites in that DNA
      replication slippage and unequal crossover recombination are important molecular
      mechanisms for LCR expansion. We support this hypothesis by demonstrating that
      the size of LCR insertions/deletions among orthologous genes depends upon length.
      Moreover, we show that LCRs enable intra-exonic recombination in a key family of
      cell-surface antigens in P. falciparum and thus likely facilitate the generation
      of antigenic diversity. We conclude with a mechanistic model for LCR evolution
      that links the pattern of LCRs within P. falciparum to its high genomic A+T
      content and recombination rate.

PMID- 16806742
TI  - New candidate species most closely related to penguins.
AB  - The phylogenetic position of the order Spenisciformes in Aves remains unclear
      despite several independent analyses based on morphological and molecular data.
      To address this issue, we determined the complete mtDNA sequence of rockhopper
      penguins. The mitochondrial genome, excluding the region from the D-loop to
      12SrRNA, was also sequenced for petrel, albatross, frigatebird, loon and grebe,
      which previous studies suggest are related to penguins. A maximum likelihood
      analysis of the phylogenetic placement of penguins with 23 birds, including 17
      species whose mtDNA sequences were previously reported, suggested that storks are
      the closest extant relatives of penguins, with 78% and 56% bootstrap supports,
      depending on the choice of outgroup species. Thus, ciconiiform birds constitute
      new candidates as the closest extant relatives of penguins (previously proposed
      candidates were either gaviiform, podicipediform, or procellariiform birds). In
      addition to this new evidence, our analysis gave evidence to some of ambiguous
      relationships in the avian tree: our analysis supported a basal split between
      passerines and other neoavians within Neoaves, and rejected the monophyly of
      Falconiformes as well as that of loons and grebes.

PMID- 16806743
TI  - Complicated RNA splicing of chicken telomerase reverse transcriptase revealed by
      profiling cells both positive and negative for telomerase activity.
AB  - Telomerase reverse transcriptase (TERT) is an essential component of the
      telomerase ribonucleoprotein complex which maintains telomeres. The objective of
      this study was to investigate chicken TERT (cTERT) alternative RNA splicing
      profiles of samples varying for telomerase activity and immortalization
      parameters. These included systems both in vivo (gastrula embryo, embryo and
      adult liver) and in vitro (chicken embryo fibroblasts (CEFs) and DT40 cells).
      Nineteen cTERT variants were discovered, which were generated through exon
      skipping, intron retention, and alternative usage of splice donor and acceptor
      sites. Three variants were predicted to introduce in-frame mutations, whereas the
      others were predicted to have premature termination codons. The number of cTERT
      variants detected ranged from 10 in adult liver to 13 in CEFs. One variant (V4)
      was found in all samples and was predicted to generate a truncated protein
      lacking telomerase catalytic activity. Interestingly, the standard TERT expected
      from the full-length transcript was expressed not only in telomerase-positive,
      but also in telomerase-negative samples. The complicated expression profiles of
      cTERT in various cell systems suggest that sophisticated regulatory pathways are
      involved in cTERT pre-mRNA editing. Further, these results support the body of
      increasing evidence that alternative splicing of TERT, both in human and chicken,
      contributes to telomerase activity regulation.

PMID- 16806744
TI  - Repetitive exposure to TGF-beta suppresses TGF-beta type I receptor expression by
      differentiated osteoblasts.
AB  - Transforming growth factor-beta (TGF-beta) has potent, cell phenotype restricted
      effects. In bone, it controls multiple activities by osteoblasts through three
      predominant receptors. Of these, the relative amounts of TGF-beta receptor I
      (TbetaRI) vary directly with TGF-beta sensitivity. The rat TbetaRI gene promoter
      includes cis-acting elements for transcription factor Runx2. Here we show
      conservation and selective partitioning of TbetaRI and retention of TGF-beta
      activity with osteoblast differentiation, Runx2 binding to the TbetaRI gene
      promoter on osteoblast chromatin, and decreased promoter activity by Runx2
      binding site mutation. Furthermore, in contrast to the stimulatory effects
      induced by single or limited exposure to TGF-beta, we found that osteoblasts
      became resistant to TGF-beta after high dose and repetitive treatment. TbetaRI
      protein, mRNA, and gene promoter activity all decreased after three daily TGF
      beta treatments, in parallel with a reduction in Runx2 protein and Runx dependent
      gene expression. In this way, sustained TGF-beta exposure can limit its own
      effectiveness by suppressing the expression of its primary signaling receptor.
      This tightly controlled system may constitute a feedback loop to protect against
      TGF-beta excess, and impose important limitations that are required for the
      progression of events during skeletal growth, remodeling and repair.

PMID- 16806745
TI  - Isolation and characterization of meridamycin biosynthetic gene cluster from
      Streptomyces sp. NRRL 30748.
AB  - Meridamycin is a non-immunosuppressive, FKBP12-binding natural macrolide with
      potential therapeutic applications in a variety of medical conditions. To set the
      stage for structural modification of meridamycin by genetic engineering, we have
      cloned and completely sequenced approximately 117 kb of DNA encompassing the
      meridamycin biosynthetic gene cluster from the producing strain, Streptomyces sp.
      NRRL 30748. Clustered in the center of the cloned DNA stretch are six genes
      responsible for the construction of the core structure of meridamycin, including
      merP encoding a non-ribosomal peptide synthase for pipecolate-incorporation, four
      PKS genes (merA-D) together encoding 1 loading module and 14 extension modules,
      and merE encoding a cytochrome P450 monooxygenase. A number of genes with
      potential pathway-specific regulatory or resistance functions have also been
      identified. The absence of the gene encoding lysine cyclodeaminase in the
      sequenced gene cluster and the rest of the genome of NRRL 30748 indicated the
      synthesis of pipecolate in this strain is not through the common lysine
      cyclodeamination route previously described for rapamycin and FK506/FK520
      biosynthesis. An efficient conjugation method has been developed for Streptomyces
      sp. NRRL 30748 to facilitate the genetic manipulation of meridamycin biosynthetic
      gene cluster. Disruption of merP resulted in the complete abolition of
      meridamycin production, proving the identity of the gene cluster. A novel
      meridamycin analogue, C36-keto-meridamycin, has been successfully generated
      through deletion of a DNA fragment encoding KR1 domain of MerA from the
      chromosomal DNA.

PMID- 16806746
TI  - Characteristics of methicillin resistant Staphylococcus aureus isolated from
      chicken meat and hospitalized dogs in Korea and their epidemiological
      relatedness.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is one of the most important
      pathogens in human and veterinary hospitals. The isolation of MRSA from animals
      and foodstuffs has been reported with an increased incidence. However,
      methicillin (oxacillin) is not used in animal husbandry or in animal hospitals in
      Korea. In this study, three pre-MRSA and one silent mecA-carrying methicillin
      susceptible S. aureus (smMSSA) were isolated from retail chicken meat, and three
      MRSA were isolated from hospitalized dogs in Korea. The three pre-MRSA isolates
      were determined to have a staphylococcal cassette chromosome mec (SCCmec) type
      III, and the smMSSA isolate was not classified. The animal hospital isolates were
      found to contain SCCmec type II. Seven and 15 S. aureus isolated from
      hospitalized humans and bovine milk, respectively, were also examined in this
      study in order to determine the epidemiological origins of MRSA. Multilocus
      sequencing typing (MLST) revealed that the chicken meat and bovine milk isolates
      were closely related to the animal hospital isolates. The SCCmec characteristics
      and MLST analyses indicated the possibility of the human to animal transmission
      of MRSA. These results highlight the importance of identifying MRSA carriers as
      well as intercepting MRSA transmission because MRSA is becoming increasingly
      widespread without any plausible relationship with the use of methicillin
      (oxacillin).

PMID- 16806747
TI  - Reduction of spermatogenesis and steroidogenesis in mice after fentin and
      fenbutatin administration.
AB  - The present study was designed to assess potential reproductive toxicity caused
      by fentin and fenbutatin in the mice. Adult male mice received i.p. injections of
      fentin hydroxide and fenbutatin oxide at a dose of 0, 10 or 25 microg/kg body
      weight on 1st, 3rd and 5th day of experimentation. Mice were sacrificed on day 25
      and analyzed for spermatogenesis and steroidogenesis. A significant decrease in
      epididymal sperm count, sperm motility, sperm viability and sperm function (HOS
      coiling) were observed in experimental mice when compared with controls. The
      decrease in sperm quantity and quality was significant in the 25 microg/kg group
      than that in the control group. The activity levels of testicular steroidogenic
      enzymes, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) were significantly decreased in treated mice
      indicating decreased steroidogenesis after organotin compounds administration.
      The levels of serum testosterone decreased with an increase in follicle
      stimulating hormone and luteinizing hormone in experimental mice when compared to
      control mice. The results suggest that fentin and fenbutatin cause impairment of
      spermatogenesis through the inhibition of testosterone production.

PMID- 16806748
TI  - Influence of season and parity on the recovery of in vivo canine oocytes by
      flushing fallopian tubes.
AB  - Assisted reproductive technology (ART) in dogs largely depends on the in vivo
      matured oocytes due to lack of a suitable in vitro maturation system. The present
      study evaluated the technique of flushing fallopian tubes to collect in vivo
      matured canine oocytes by laparotomy, and determined the effects of seasons, and
      parity of donor bitches on the success of oocyte retrieval. Oocytes were
      retrieved from anesthetized bitches by laparotomy. About 7 ml of TCM-199
      supplemented with HEPES was used to flush each individual fallopian tube. Oocytes
      were categorized as good, fair, poor, immature or aged based on the nuclear
      stage, cumulus cell layers, color and homogeneity of ooplasm. Oocytes categorized
      as being good or fair were considered usable, while poor, aged or immature
      oocytes were considered unusable for ART. A significantly higher number of
      oocytes per bitch were retrieved during the spring (11.2) compared to the winter
      (7.9). The oocyte recovery rates were 89.4, 92.2, 89.7 and 89.3% for spring,
      summer, autumn, and winter, respectively. The highest percentage of usable
      oocytes (74.7%) was retrieved during autumn (P>0.05). The number of oocytes was
      influenced by the parity of the donor bitch. Significantly more oocytes were
      collected from the multiparous bitches (10.3) compared to nulliparous bitches
      (7.7). The percentage of usable oocytes was more in multipara (71.5%) compared to
      nullipara (64.7%) (P>0.05). Collection of in vivo produced oocytes by laparotomy
      represents a potential source of matured oocytes for ART in dogs.

PMID- 16806749
TI  - Ovarian steroids and the human breast: regulation of stem cells and cell
      proliferation.
AB  - Ovarian steroidal control of mammary gland proliferation and differentiation is
      not well defined in the human. We therefore developed the athymic nude mouse
      model in which intact normal human breast tissue is xenografted subcutaneously
      and treated with human physiological serum levels of oestrogen (E) and/or
      progesterone (P). We showed that: (i) E, and not P, is the major steroid hormone
      inducing proliferation of epithelial cells in the adult non-pregnant, non
      lactating breast; (ii) E induces progesterone receptor (PR) expression; and (iii)
      PR expression is maximally induced at low E concentrations while a higher amount
      of E was required to induce proliferation. Using double label immuno
      fluorescence, we demonstrated that cells expressing the oestrogen receptor-alpha
      (ER alpha) invariably contained the PR but that steroid receptor expression and
      cell proliferation (Ki67 antigen) were dissociated. Recently, we have
      demonstrated that some ER alpha/PR-positive epithelial cells are quiescent breast
      stem cells suggesting that they act as "steroid hormone sensors" that secrete
      paracrine factors to regulate the proliferative activity of adjacent ER alpha/PR
      negative epithelial cells. The dissociation between steroid receptor expression
      and cell proliferation in normal epithelium was lost at an early stage in ER
      alpha/PR-positive breast tumour formation perhaps indicating that they arise from
      deregulation of the normally quiescent breast stem cells.

PMID- 16806750
TI  - Impact of seafood and fruit consumption on bone mineral density.
AB  - OBJECTIVES: Over the past decade, dietary choices and nutrition have proven to be
      major modulators of bone mineral density (BMD) in men and women. We investigated
      environmental determinants, specifically dietary habits, of BMD by using multiple
      regression models in a rural Chinese population. METHODS: BMDs were measured at
      the hip and total body in 5848 men and 6207 women, aged 25-64. Dietary and
      supplemental intakes were assessed by a simple, one-page questionnaire tailored
      to collect nutritional information from large rural populations. Another
      questionnaire was used to collect information on the subjects' age, disease
      history, smoking, alcohol consumption, physical activity as well as women's
      menstrual status and reproductive history. Multiple regression models were used
      to assess the relationships among dietary variables and BMD, after adjusting for
      age, BMI (body mass index), weight, occupation, smoking status, and alcohol
      consumption. RESULTS: Increasing seafood consumption was significantly associated
      with greater BMD in women (p<0.001), especially those consuming more than 250 g
      per week of seafood. One thousand and three hundred and twenty-four men and 1479
      women consumed >250 g of fruit per week. Higher fruit intake was found to be
      significantly associated with higher BMD in both sexes (p<0.05). High vegetable
      consumption, however, did not positively impact BMD. CONCLUSIONS: This study with
      its large population size has identified preventive measures, as well as some
      risk factors, involved in bone loss and osteoporosis. Our results highlight the
      importance of several dietary variables as significant determinants of BMD. It
      also emphasizes the role of dietary intake in general and shows that specific
      foods, such as fruits and seafood, can positively impact BMD.

PMID- 16806751
TI  - Kinetic model of drug distribution in the urinary bladder wall following
      intravesical instillation.
AB  - Intravesical administration of cytotoxic agents is commonly used in urological
      practice for treatment of superficial bladder cancer. The leading motive is
      optimisation of drug delivery near the site of action and reduction of systemic
      toxicity. Bladder pharmacokinetics is complicated by several mechanisms. The
      objectives of this work were to develop a kinetic model of drug distribution in
      the bladder wall following intravesical instillation and to study the effect of
      various parameters on tissue and systemic drug exposure and explore the potential
      benefits of permeability enhancing effects of chitosan (CH) and polycarbophil
      (PC) through simulation. Key elements of the model are variable urinary drug
      concentration due to urine formation and voiding, biphasic diffusion in the
      bladder tissue and systemic absorption. Model parameters were estimated from
      bladder-tissue concentration profiles obtained in previous in vitro experiments
      with pipemidic acid (PPA) as a model drug. The results support further
      investigations on application of CH and PC in intravesical drug delivery. Both
      polymers increase permeability of the bladder wall by diffusion enhancement in
      the urothelium and presumably by improving the contact with the bladder surface.
      The developed mathematical model could serve for optimisation of intravesical
      drug delivery and future development of intravesical drug delivery systems.

PMID- 16806752
TI  - In vitro release and in vivo absorption in beagle dogs of meloxicam from Eudragit
      FS 30 D-coated pellets.
AB  - The objective of this study was to develop meloxicam-loaded colon-specific
      pellets coated with Eudragit FS 30 D and further evaluate their in vitro release
      and in vivo absorption in beagle dogs. Meloxicam-loaded cores (drug loading,
      4.8%, w/w) were prepared by layering drug-binder (HPMC)-solubilizer (beta
      cyclodextrin) solution onto nonpareils (710-850 microm) and then coated with a
      copolymer of methyl acrylate, methyl methacrylate and methacrylic acid (Eudragit
      FS 30 D). The obtained pellets with 15% (w/w) coating level had a spherical form
      and a smooth surface with coating thickness approximately 28 microm. The in vitro
      drug release from the pellets was pH-dependent with sufficient gastric resistance
      (pH 1.2: no release; pH 6.8: 6%; pH 7.0: 52%; pH 7.2: 100%; pH 7.4: 100%, after 3
      h incubation). In vivo study was carried out using pentagastrin-pretreated beagle
      dogs. The onset of meloxicam absorption from the coated pellets with 15% (w/w)
      Eudragit FS 30 D (3.0+/-0.8 h) was significantly delayed (p<0.05) compared to
      that from the uncoated drug-layered cores (0.6+/-0.3 h). The area under the
      meloxicam plasma concentration-time curve (AUC(0-->96)(h) was not significantly
      different between the two preparations (p>0.05), although AUC(0-->96)(h) obtained
      after oral administration of coated pellets (142.5+/-59.6 microg h/ml) was lower
      than that obtained after administration of uncoated drug-layered cores (180.8+/
      61.9 microg h/ml). These results suggested that meloxicam could be delivered to
      the colon with 15% (w/w) coating level of Eudragit FS 30 D and this polymer
      coating had no significant influence on the relative bioavailability of meloxicam
      of the pellets.

PMID- 16806753
TI  - Swellable drug-polyelectrolyte matrices (SDPM) of alginic acid characterization
      and delivery properties.
AB  - This study deals with the development and characterization of the delivery
      properties of swellable drug-polyelectrolyte matrices (SDPM) of alginic acid
      (AA). Complexes (AA-D)(x) in solid state were obtained by neutralization of AA
      with different molar proportions (x) of model basic drugs (D), in which D is
      atenolol, metoclopramide and propranolol. They were characterized by DSC, IR and
      X-ray diffraction. Matrices prepared by compaction of (AA-D)(x) alone or in a
      mixture with sodium alginate (NaAA) were subjected to measurements of solvent up
      take, release kinetics and erosion in three media (water, buffer of pH 6.8 and
      0.01 M HCl). In addition, the dynamics of swelling was also evaluated. All SDPM
      assayed exhibited a remarkable zero order of delivery in water and buffer of pH
      6.8 and also in two-step delivery experiments: 2 h in acid medium followed by a
      second step at pH 6.8. Experimental results indicate that the erosion of the
      hydrogel layer is the main delivery process. Delivery rate, can be modulated
      either by varying the composition of (AA-D)(x) or by diluting it with NaAA.

PMID- 16806754
TI  - Influence of sodium metabisulfite and glutathione on the stability of vitamin C
      in O/W emulsion and extemporaneous aqueous gel.
AB  - Vitamin C exerts several functions on skin as collagen synthesis, depigmentant
      and antioxidant activity. Vitamin C is unstable in the presence of oxygen,
      luminosity, humidity, high temperatures and heavy metals, which presents a
      significant challenge to the development of cosmetic formulations. Therefore, the
      utilization of an effective antioxidant system is required to maintain the
      vitamin C stability. The purpose of this research work was to develop prototypes
      of cosmetic formulations, as O/W emulsion and extemporaneous aqueous gel,
      containing vitamin C and to evaluate the influence of sodium metabisulfite (SMB)
      and glutathione (GLT), as antioxidants, on the stability of the active substance.
      A HPLC stability-indicating method was developed and validated for this study and
      stability assays were performed in 90 and 26 days and storage conditions were
      5.0+/-0.5, 24+/-2 and 40.0+/-0.5 degrees C. The HPLC stability-indicating method
      showed linearity (r(2)>0.99), specificity, R.S.D.<1.22% and accuracy/recovery
      ranging from 95.46 to 101.54%. Preparations with SMB or GLT and the antioxidant
      free presented results statistically distinct, demonstrating the necessity of the
      antioxidant system addition. O/W emulsions with SMB or GLT retained the vitamin C
      content >90.38% stored at 5.0+/-0.5 and 24+/-2 degrees C. For the aqueous gel
      with SMB or GLT, the active substance concentration was maintained >94.03%.
      Considering the vitamin C stability, the SMB and the GLT showed to be
      statistically adequate, as antioxidants, for the cosmetic formulations.

PMID- 16806755
TI  - Deformable liposomes and ethosomes: mechanism of enhanced skin delivery.
AB  - Despite intensive research, the mechanisms by which vesicular systems deliver
      drugs into intact skin are not yet fully understood. In the current study,
      possible mechanisms by which deformable liposomes and ethosomes improve skin
      delivery of ketotifen under non-occlusive conditions were investigated. In vitro
      permeation and skin deposition behavior of deformable liposomes and ethosomes,
      having ketotifen both inside and outside the vesicles (no separation of free
      ketotifen), having ketotifen only inside the vesicles (free ketotifen separated)
      and having ketotifen only outside the vesicles (ketotifen solution added to empty
      vesicles), was studied using rabbit pinna skin. Results suggested that both the
      penetration enhancing effect and the intact vesicle permeation into the stratum
      corneum might play a role in improving skin delivery of drugs by deformable
      liposomes, under non-occlusive conditions, and that the penetration enhancing
      effect was of greater importance in case of ketotifen. Regarding ethosomes,
      results indicated that ketotifen should be incorporated in ethosomal vesicles for
      optimum skin delivery. Ethosomes were not able to improve skin delivery of non
      entrapped ketotifen.

PMID- 16806756
TI  - Optimization of poorly compactable drug tablets manufactured by direct
      compression using the mixture experimental design.
AB  - The poor flowability and bad compressibility characteristics of paracetamol are
      well known. As a result, the production of paracetamol tablets is almost
      exclusively by wet granulation, a disadvantageous method when compared to direct
      compression. The development of a new tablet formulation is still based on a
      large number of experiments and often relies merely on the experience of the
      analyst. The purpose of this study was to apply experimental design methodology
      (DOE) to the development and optimization of tablet formulations containing high
      amounts of paracetamol (more than 70%) and manufactured by direct compression.
      Nineteen formulations, screened by DOE methodology, were produced with different
      proportions of Microcel 102, Kollydon VA 64, Flowlac, Kollydon CL 30, PEG 4000,
      Aerosil, and magnesium stearate. Tablet properties, except friability, were in
      accordance with the USP 28th ed. requirements. These results were used to
      generate plots for optimization, mainly for friability. The physical-chemical
      data found from the optimized formulation were very close to those from the
      regression analysis, demonstrating that the mixture project is a great tool for
      the research and development of new formulations.

PMID- 16806757
TI  - Lipoplexes with biotinylated transferrin accessories: novel, targeted, serum
      tolerant gene carriers.
AB  - Novel transfecting assemblies comprising biotinylated cationic liposomes, DNA and
      tribiotinylated transferrin-streptavidin (streptavidin(bio3-transferrin))
      accessories have been prepared, characterized and evaluated for toxicity and DNA
      delivery capability in human cervical carcinoma cells (HeLa). Two new lipophilic
      cholesteryl-based biotin derivatives, biotinylcholesterylformylhydrazide (MSB1)
      and aminohexanoylbiotinylcholesterylformylhydrazide (MSB2) provided docking
      points for streptavidin(bio3-transferrin) on cationic liposomes which were
      formulated with N,N-dimethylaminopropylaminylsuccinylcholesterylformylhydrazide
      (MS09) and dioleoylphosphatidylethanolamine (DOPE) in a 2:48:50 molar ratio.
      Ethidium dye displacement assays and gel retardation studies suggest that in
      ternary complexes, the DNA is electrostatically bound to the cationic liposomes
      while transferrins remain liposome-bound through streptavidin-biotin
      interactions. Assemblies fully protected plasmid DNA from serum nuclease
      digestion over a range of liposome:pGL3 DNA ratios (3-8:1, w/w) and exhibited low
      growth inhibition of HeLa cells (circa 5%) at the optimal transfection
      composition for streptavidin(bio3-transferrin):liposome:pGL3 DNA of 10:6:1
      (w/w/w). Transfection levels, which were twice those of untargeted lipoplexes
      containing MSB1 or MSB2, were not significantly diminished in the presence of 10%
      foetal bovine serum. Excess transferrin (200 microg per well) reduced
      transfection levels to those of untargeted complexes, supporting the notion that
      at least 50% of ternary complexes gained entry into the cervical carcinoma cells
      by receptor mediation. Conversely, transfection levels with untargeted lipoplexes
      were only slightly reduced in the presence of transferrin at the same
      concentration.

PMID- 16806758
TI  - Altered pharmacokinetics of paclitaxel by the concomitant use of morin in rats.
AB  - The purpose of this study was to investigate the effect of morin on the
      pharmacokinetics of orally and intravenously administered paclitaxel in rats.
      Pharmacokinetic parameters of paclitaxel were determined in rats after an oral
      (30 mg kg(-1)) or intravenous (3 mg kg(-1)) administration of paclitaxel to rats
      in the presence and absence of morin (3.3 and 10 mg kg(-1)). Compared to the
      control given paclitaxel alone, pretreatment with morin 30 min prior to the oral
      administration of paclitaxel increased C(max) and AUC of paclitaxel by 70-90% and
      30-70%, respectively, while there was no significant change in T(max) and
      terminal plasma half-life (T(1/2)) of paclitaxel. Consequently, absolute and
      relative bioavailability values of paclitaxel in the rats after the pretreatment
      with morin were significantly higher (p<0.05) than those from the control. In
      contrast, following an intravenous administration of paclitaxel (3.3 mg kg(-1)),
      the pharmacokinetic profiles of paclitaxel were not altered significantly in the
      presence of morin. Those results suggest that the enhanced oral exposure of
      paclitaxel should be mainly due to the inhibition effect of morin on the
      gastrointestinal extraction of paclitaxel during the intestinal absorption.
      Therefore, the concurrent use of morin or morin-containing dietary supplement may
      provide a therapeutic benefit in the oral delivery of paclitaxel.

PMID- 16806759
TI  - Investigation on a new scleroglucan/borax hydrogel: structure and drug release.
AB  - The aim of this work is to elucidate the structure of the new hydrogel prepared
      with scleroglucan (Sclg) and borax, suitable for drug delivery, applying
      theoretical approaches, and to explain its very peculiar swelling. The possible
      linkages with borate ions have been investigated and original parameters for the
      4,6-gluco-borate moiety have been introduced. The structures relative to the Sclg
      chains in the presence of borax and the possible mutual arrangements among the
      triple helices are given. According to molecular dynamics simulations, the most
      probable assembly of the chains in the network is proposed, without and in the
      presence of three tested model drugs with different molecular dimensions:
      theophylline (TPH), Vitamin B12 (Vit. B12) and myoglobin (MGB). The hydrogel
      supramolecular structure, formed via chemical and physical linkages among the
      polysaccharidic chains, is built up taking into account the steric hindrance of
      the entrapped molecules. It is shown that molecular dynamics analysis can be a
      useful tool capable to shed some light on the anomalous swelling of the hydrogel,
      suitable for drug release, giving a new insight on the network structure and the
      release rate of the guest molecules.

PMID- 16806760
TI  - Folk medical uses of plant foods in southern Appalachia, United States.
AB  - An analysis of information obtained from interviews with 660 older native
      inhabitants of the southern Appalachian region in the United States indicates
      that plant foods, especially cultivars and materials processed from them, and
      some wildcrafted plant foods as well, constituted the bulk of the folk materia
      medica in the 1920s and 1930s. Aside from their use for the treatment of common
      ailments, many plant foods were, and still are to a lesser extent, valued in the
      region for cleaning and building blood, cleaning the bowel, and as a source of
      vitamins and minerals. The dependence on plant foods and wildcrafted medicinal
      plants, however, appears to have diminished considerably in recent years.

PMID- 16806761
TI  - Nicotiflorin reduces cerebral ischemic damage and upregulates endothelial nitric
      oxide synthase in primarily cultured rat cerebral blood vessel endothelial cells.
AB  - Nicotiflorin is a flavonoid glycoside extracted from a traditional Chinese
      medicine Flos Carthami. In the current study, we investigated the neuroprotective
      effect of nicotiflorin on a transient focal cerebral ischemia-reperfusion model
      in rats. Nicotiflorin (2.5-10 mg/kg) administered after onset of ischemia
      markedly reduced brain infarct volume by 24.5-63.2% and neurological deficits.
      Also the effect of nicotiflorin on endothelial nitric oxide synthase (eNOS)
      activity, mRNA and protein expression after hypoxia-reoxygenation (H-R) treatment
      was investigated in an in vitro model mimic cerebrum ischemia-reperfusion in
      vivo. After total 4 h hypoxia and 12 h reoxygenation, eNOS activity, mRNA and
      protein levels in the primarily cultured rat cerebral blood vessel endothelial
      cells treated with nicotiflorin (25-100 microg/ml) 2 h after onset of hypoxia
      were significantly higher than eNOS activity, mRNA and protein levels in the pure
      H-R cells and also higher than eNOS activity, mRNA and protein levels in cells
      cultured under normoxic conditions. The results demonstrated that nicotiflorin
      had a protective effect against cerebral ischemic damage. The results also gave
      an important elucidation for the mechanism underlying the protective effect at
      the cellular level.

PMID- 16806762
TI  - Ondamtanggamibang protects neurons from oxidative stress with induction of heme
      oxygenase-1.
AB  - Ondamtanggamibang (ODG) has been used as a remedy to treat psychological anxiety
      and depression in Oriental medicine. In this study, we found the protective
      effects of ODG against oxidative stress by induction of the antioxidative enzyme,
      heme oxygenase (HO)-1 in neuronal PC12 cells. Pretreatment with ODG extract
      protected neuronal cells from damage induced by H(2)O(2) and 6-hydroxydopamine (6
      OHDA), but simultaneous treatment with ODG extract did not. ODG also inhibited
      the intracellular reactive oxygen species elevation by H(2)O(2) and 6-OHDA. ODG
      stimulation strongly induced the expression of HO-1 in PC12 cells. The protective
      effect of ODG extract on oxidative stress-induced damage was suppressed by HO
      inhibitor, zinc protoporphyrin IX (ZnPP-IX). Taken together, these data suggest
      that ODG treatment has potential protective effects in neuronal cells under
      oxidative stress.

PMID- 16806763
TI  - Wound healing potential of Tephrosia purpurea (Linn.) Pers. in rats.
AB  - Tephrosia purpurea is a well-known herb for its hepatoprotective, anticancer,
      antiulcer, antibacterial and in healing bleeding piles, etc. The present study
      was aimed for wound healing potential of ethanolic extract of Tephrosia purpurea
      (aerial part) in the form of simple ointment using three types of wound models in
      rats as incision wound, excision wound and dead space wound. The results were
      comparable to standard drug Fluticasone propionate ointment, in terms of wound
      contraction, tensile strength, histopathological and biochemical parameters such
      as hydroxyproline content, protein level, etc. Histopathological study showed
      significant (P<0.05) increase in fibroblast cells, collagen fibres and blood
      vessels formation. All parameters were observed significant (P<0.05) in
      comparison to control group.

PMID- 16806764
TI  - KIOM-79 inhibits LPS-induced iNOS gene expression by blocking NF-kappaB/Rel and
      p38 kinase activation in murine macrophages.
AB  - We demonstrate that KIOM-79, combined extracts obtained from Magnolia
      officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis,
      inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of RAW
      264.7 cells with KIOM-79 inhibited LPS-stimulated nitric oxide production in a
      dose-related manner. Immunohisto-chemical staining of iNOS and RT-PCR analysis
      showed that the decrease of NO was due to the inhibition of iNOS gene expression.
      Immunostaining of p65, EMSA, and reporter gene assay showed that KIOM-79
      inhibited NF-kappa/Rel nuclear translocation, DNA binding, and transcriptional
      activation, respectively. Western immunoblot analysis of p38 kinase showed KIOM
      79 significantly inhibited the phosphoylation of p38 kinase which is important in
      the regulation of iNOS gene expression. Collectively, this series of experiments
      indicates that KIOM inhibits iNOS gene expression by blocking NF-kappa/Rel and
      p38 kinase signaling. Due to the critical role that NO release plays in mediating
      inflammatory responses, the inhibitory effects of KIOM-79 on iNOS suggest that
      KIOM-79 may represent a useful anti-inflammatory agent.

PMID- 16806765
TI  - Sudden infant death syndrome (SIDS)--standardised investigations and
      classification: recommendations.
AB  - Sudden infant death syndrome (SIDS) still accounts for considerable numbers of
      unexpected infant deaths in many countries. While numerous theories have been
      advanced to explain these events, it is increasingly clear that this group of
      infant deaths results from the complex interaction of a variety of heritable and
      idiosyncratic endogenous factors interacting with exogenous factors. This has
      been elegantly summarised in the "three hit" or "triple risk" model.
      Contradictions and lack of consistencies in the literature have arisen from
      diverse autopsy approaches, variable applications of diagnostic criteria and
      inconsistent use of definitions. An approach to sudden infant death is outlined
      with discussion of appropriate tissue sampling, ancillary investigations and the
      use of controls in research projects. Standardisation of infant death
      investigations with the application of uniform definitions and protocols will
      ensure optimal investigation of individual cases and enable international
      comparisons of trends.

PMID- 16806766
TI  - Demands on scientific studies: vitality of wounds and wound age estimation.
AB  - Research on vitality and wound age estimation belongs to the classic fields in
      forensic medicine. Despite large literature data there is still considerable
      demand of further research and practical transfer of knowledge and techniques to
      daily casework. Scientific studies must fulfil basic criteria as to appropriate
      methods, selection of case material, analysis of results and quality control.
      Nowadays, immunohistochemistry, biochemical tests and molecular biological
      techniques are mainly used studying questions of vitality and wound age.
      Investigations can be based on human tissue samples (autopsy material, vital
      specimens) or animal experiments. The possibilities, advantages and disadvantages
      of these study designs are described. Indispensable is the use of appropriate
      control groups or control samples and a sufficient case number which permits
      statistical analysis. Main strategy is to minimize variations due to methods and
      investigators as the unavoidable biological variation of vitality processes and
      wound repair is large enough.

PMID- 16806767
TI  - Microsatellite autosomal genotyping data in four indigenous populations from El
      Salvador.
AB  - Fifteen microsatellite loci (D3S1358, TH01, D21S11, D18S51, PENTA E, D5S818,
      D13S317, D7S820, D16S539, CSF1PO, PENTA D, vWA, D8S1179, TPOX, and FGA) have been
      genotyped in four indigenous populations from El Salvador (Central America),
      namely, Conchagua, Izalco, Panchimalco, and San Alejo. Here we have obtained
      values for several indices of forensic interest for these population samples.
      Population differentiation test showed no significant statistical differences
      between these four populations, and an AMOVA test indicates that most of the
      genetic variation (approximately 100%) occurs within individuals. Population
      pairwise genetic comparisons with other population samples seem to indicate the
      existence of a major Native American component in the populations from El
      Salvador.

PMID- 16806768
TI  - STR data for the 15 AmpFlSTR identifiler loci in the Western Romanian population.
AB  - Allele frequencies for the 15 tetranucleotide short tandem repeat loci contained
      in the AmpFlSTR Identifiler kit were obtained from a population sample of 219
      unrelated individuals born in the western part of Romania.

PMID- 16806769
TI  - Demands on scientific studies in clinical toxicology.
AB  - Scientific case studies in clinical toxicology on single cases or series of
      similar cases should document sufficient information on the clinical methodology
      and observations, the medical laboratory methodology and results, the
      toxicological analyses methodology and results, the source of used reference
      values for drug/poison concentrations and kinetics with critical discussion of
      such values, a description and discussion of the toxicodynamic, the toxicological
      and the kinetic properties of the detected drugs and/or poisons. The data
      management, statistical analysis and finally the clinical and/or analytical
      outcomes must also be described and discussed in correlation to already published
      data. Statistical methods used for evaluation of clinical as well as for
      analytical data should be described in detail. When possible, quantitative
      findings should be presented with appropriate indicators of measurement error or
      uncertainty. Requirements for such studies are discussed.

PMID- 16806770
TI  - Analysis of 15 STR loci in Chinese population from Sichuan in West China.
AB  - Allele frequencies for 15 STR loci found in PowerPlex 16 System kit were
      determined in a sample of 200 unrelated individuals living in Sichuan area in
      west China. The values of observed heterozygosity (Ho), power of discrimination
      (PD), probability of paternity exclusion (PE) and polymorphism information
      content (PIC) were calculated. All loci were in accordance with Hardy-Weinberg
      equilibrium (p<0.05). The obtained frequency distributions were compared with
      other previously reported population data.

PMID- 16806771
TI  - Editorial on the recommendations of the DNA commission of the ISFG on the
      interpretation of mixtures.

PMID- 16806772
TI  - The use of forensic botany and geology in war crimes investigations in NE Bosnia.
AB  - From 1997 to 2002 the United Nations International Criminal Tribune for the
      former Yugoslavia (ICTY) undertook the exhumation of mass graves in NE Bosnia as
      part of the war crimes investigations aimed at providing evidence for the
      prosecution of war criminals in The Hague. This involved the location and
      exhumation of seven former mass graves (primary sites) dug following the fall of
      Srebrenica in July 1995. These primary mass graves were secretly and hurriedly
      exhumed three months later and most of the bodies or body parts transported and
      reburied in a large number of secondary sites many of which were subsequently
      exhumed by ICTY. The aim of the pollen and soil/sediment studies was to provide
      an 'environmental profile' of the original site of the samples and use this to
      match the relocated bodies to the original mass graves. This was part of
      completing the chain of evidence, providing evidence of the scale and
      organization of the original atrocities and the subsequent attempts to conceal
      the evidence related to them. All the primary sites were located in areas of
      contrasting geology, soils and vegetation, and this allowed matching of the
      sediment transported in intimate contact with the bodies to the original burial
      sites, which in some cases were also the execution sites. In all, over 24 sites
      were investigated, over 240 samples collected and analyzed under low power
      microscopy and 65 pollen sub-samples fully analyzed. The pollen and sediment
      descriptions were used in conjunction with the mineralogy (using XRD) of primary
      and secondary sites in order to provide matches. These matches were then compared
      with matching evidence from ballistic studies and clothing. The evidence has been
      used in court and is now in the public domain. It is believed this is the first
      time 'environmental profiling' techniques have been used in a systematic manner
      in a war crimes investigation.

PMID- 16806773
TI  - Homicide-suicide - an event hard to prevent and separate from homicide or
      suicide.
AB  - Suicide preceded by homicide is a rare but tragic event that often shocks the
      whole community. Annual rates show considerable variation, though not as great as
      the incidence of homicides. Within the industrialized nations, Finland's
      prevalence rates for homicide-suicide have been mid-range. The National Suicide
      Prevention Project recorded and carefully analysed all suicides committed in
      Finland during a 12-month period. In this material of almost 1400 suicides, 10
      verified homicide-suicide cases were found. The perpetrator was male in all but
      one case, and all the victims were family, 9/10 being spouses and/or children.
      The most typical homicide-suicide seemed to be a man shooting a family member
      during a separation process. No perpetrator was found suffering from a psychotic
      disorder but three had major depression. The homicide-suicides were compared with
      the suicides and statistically significant differences emerged in two variables:
      shooting was more often the method used in the homicide-suicide cases, which,
      furthermore, were more likely to involve a divorce or recent rupture in another
      long-term intimate relationship. Sharing few common variables with either
      homicide or suicide, homicide-suicide appears to be a distinct phenomenon whose
      prevention would seem to be extremely difficult on the individual level. Since
      shooting is the most common method of homicide-suicide, firearm licenses should
      be more restricted.

PMID- 16806774
TI  - Liver histopathology of fatal phosphine poisoning.
AB  - Two commonly used pesticides in agriculture are phosphides of aluminium and zinc.
      Both of these metal phosphides act through elaboration of toxic phosphine gas.
      The poisoning in Iran is mostly oral and suicidal. Phosphine is rapidly absorbed
      throughout the gastrointestinal tract after ingestion and it is partly carried to
      the liver by the portal vein. In this study the liver histopathology of fatal
      poisoning is scrutinized. A descriptive, retrospective study was performed on 38
      fatal phosphine poisonings. The slides of liver specimens of the cases were
      retrieved and studied separately by two pathologists. The poisoning was suicidal
      in 33 (86.5%) of cases. Portal inflammation was negligible in 37 cases and only
      in one of the cases, a moderate degree of chronic inflammation accompanied by
      granuloma formation was observed. Major histopathologic findings were as follows:
      mild sinusoidal congestion; 12 cases (31.6%), severe sinusoidal congestion; 25
      cases (45.8%), central vein congestion; 23 cases (60.5%), centrilobular necrosis;
      3 cases (7.9%), hepatocytes nuclear fragmentation; 6 cases (15.8%), sinusoidal
      clusters of polymorphonuclear leukocytes; 12 cases (31.6%), and mild
      macrovesicular steatosis; 5 cases (13.2%). Fine isomorphic cytoplasmic vacuoles
      were observed in 36 cases (94.7%). These vacuoles were distributed uniformly in
      all hepatic zones in the majority (75%) of cases. This study reveals that the
      main histopathologic findings of fatal phosphine poisoning in the liver are fine
      cytoplasmic vacuolization of hepatocytes and sinusoidal congestion.

PMID- 16806775
TI  - Study types and study issues in clinical medicine.

PMID- 16806776
TI  - Human Y-specific STR haplotypes in population of Serbia and Montenegro.
AB  - Nine Y chromosome short tandem repeat (STR) loci (DYS19, DYS385, DYS389I,
      DYS389II, DYS390, DYS391, DYS392 and DYS393) were analyzed in group of 237
      unrelated healthy males from population of Serbia and Montenegro in order to
      assess the frequencies of Y haplotypes. We observed 174 different haplotypes of
      which 146 (61.6%) were seen only once. Y-STR allelic frequencies in Serbia and
      Montenegro, in general, correspond to other European populations, except for the
      DYS19, DYS385 and DYS389II loci.

PMID- 16806777
TI  - Clinical and EEG characteristics of benign rolandic epilepsy in Chinese patients.
AB  - We retrospectively evaluated the clinical and electroencephalogram (EEG)
      characteristics of benign rolandic epilepsy (BRE) in Chinese children. Two
      hundred and seventy-six patients with BRE were enrolled in this study. All
      patients had their first seizure between the ages of 3 and 12 years. 39.5% (109
      cases) of patients ceased to have further BRE seizures by the age of 6 years,
      93.1% (257 cases) recovered by the age of 12 years and 96.7% (267 cases)
      recovered by the age of 18 years. Two hundred and twenty-seven patients suffered
      only simple partial seizures, whereas 49 patients suffered generalized seizures
      from onset of BRE. The EEG scans of 239 patients showed repetitive diphasic
      spikes or sharp waves with high amplitude, which were most dominant in the
      central or centrotemporal areas. The spikes were confined to one hemisphere in
      180 patients and occurred bilaterally in 59 patients. Ninety-eight patients were
      treated with antiepileptic drugs (AEDs): carbamazepine (CBZ) or valproate (VPA).
      The study showed that, in Chinese children, BRE is remarkably characteristic in
      its clinical and EEG presentation. Although BRE is usually benign in terms of
      ease of control with AEDs and spontaneous seizure remission, for those patients
      with a high frequency of seizures, AEDs should be prescribed positively.

PMID- 16806778
TI  - Zonisamide eradicated paroxysmal headache with EEG abnormalities triggered by
      hypertensive encephalopathy due to purpura nephritic syndrome.
AB  - Generally, prognosis of hypertensive encephalopathy in childhood is favorable. We
      reported a 5-year-old girl who presented with a headache attack and EEG
      abnormalities after hypertensive encephalopathy due to purpura nephritis. The
      patient had suffered from hypertensive encephalopathy due to purpura nephritis,
      which soon ameliorated. Five months later, she developed attacks of headache,
      vomiting and disturbed consciousness with left side-predominant EEG
      abnormalities. Although carbamazepine and sodium valproate failed to improve her
      condition, zonisamide eradicated both the symptoms and EEG abnormalities, and an
      attack has not reoccurred for 5 years since completion of her treatment. It is
      noteworthy that delayed-onset complications can occur in child hypertensive
      encephalopathy, cases of which should be followed up prudently. Zonisamide should
      be considered for treatment of attacks of headaches with an epileptic character.

PMID- 16806779
TI  - [A mild blackwater fever].
AB  - We report a highly probable case of moderately severe blackwater fever. A French
      woman, living in Guinea Bissau, was used to taking self-medication halofantrine
      for malaria. On this occasion, she felt unusual chills and pyrexia after a non
      documented bout of malaria, followed by nausea, then jaundice with dark-red
      urines despite another treatment with halofantrine. A sepsis was eliminated by
      two negatives thick peripheral blood drop examinations. Hemolysis was noted with
      8.1 g/dl of hemoglobin, Coombs positive, and LDH at 1,452 IU/l, associated to
      renal failure with 34 ml per minute of clearance. The outcome was favourable with
      rehydration. Blackwater fever has been described with the three aminoalcohols,
      but mainly in severe presentations. Clinicians are not familiar with this
      disease, even though it has major therapeutic implications: quinine,
      halofantrine, and mefloquine become strictly contra-indicated. Moderate forms may
      be unknown, and this observation should be taken into account to prevent
      mistreatment in future patients.

PMID- 16806780
TI  - [Cases of imported cholera in France, summer 2005. A. Tarantola for the incident
      management teams].
AB  - Cholera is a bacterial infection, which causes digestive symptoms and massive
      diarrhoea. It may lead to dehydration and death if appropriate medical management
      is not rapidly initiated. Most cases of infection by choleric vibrio, however,
      remain symptom-free or may mimic common gastroenteritis. A review of two cases of
      imported cholera in France in the summer of 2005 and the community- and hospital
      based investigation, which they triggered, enabled the incident management teams
      to assess risks of transmission. There were no secondary cases among 58 hospital
      contacts and 15 family contacts of the cases. Clinicians will find a discussion
      of possible clinical presentations and the risk of secondary transmission, in the
      context of progressing epidemics in countries, which have maintained close ties
      with France.

PMID- 16806781
TI  - Long-term treatment with N-acetylcysteine, but not caloric restriction, protects
      mesenchymal stem cells of aged rats against tumor necrosis factor-induced death.
AB  - The survival of mesenchymal stem cells (MSCs) to tumor necrosis factor alpha
      (TNFalpha) stimulation was evaluated after a long-term antioxidant treatment, or
      caloric restriction, in aged rats. MSCs were isolated from bone marrow of 30
      month-old rats which orally received N-acetylcysteine in the last 18 months. The
      necrotic cell death-induced in vitro by TNFalpha, determined by trypan blue
      exclusion, was markedly attenuated in MSCs obtained from treated vs. control aged
      rats (percent mean+/-SEM: 10.9+/-2.17 vs. 17.8+/-0.53; p<0.05). Also, the
      proliferation rate of MSCs from control, but not N-acetylcysteine-treated, aged
      rats evaluated up to 2 weeks was significantly higher than that of MSCs from
      younger (4-month-old) rats. No significant effect was observed relative to the
      parameters investigated when the aged rats were previously subjected to a
      hypocaloric diet for 18 months. In conclusion, a prolonged supplementation with N
      acetylcysteine in rats can increase resistance to necrotic death of MSCs and may
      also counteract an excessive rate of MSC proliferation.

PMID- 16806782
TI  - Multiple roles of FOXO transcription factors in mammalian cells point to multiple
      roles in cancer.
AB  - The FOXO family of transcription factors has been implicated in several cellular
      processes including cell cycle arrest, cell death and protection from stress
      stimuli. FOXO function is influenced by multiple signaling pathways. Many of
      these pathways are known to be misregulated in cancer. Perturbation of FOXO
      function leads to uncontrolled cell proliferation and accumulation of DNA damage.
      It is becoming clear that active FOXO proteins play an important role in keeping
      cells in check and inactivation of FOXO proteins is associated with
      characteristics of cancer cells. FOXO proteins may represent new therapeutic
      targets for a broad spectrum of cancers.

PMID- 16806783
TI  - Colorectal stenting for colonic obstruction: the indications, complications,
      effectiveness and outcome--5 year review.
AB  - INTRODUCTION: Currently self-expanding metallic stents are being used for
      palliation and acute decompression of colonic obstruction. The aim of this study
      is to review our experience of using these metallic stents over a 5-year period.
      MATERIALS AND METHODS: Case records of 102 patients who had colorectal stenting
      between 1998 and 2004 were reviewed retrospectively. The indications for
      colorectal stenting, efficacy of the procedure in relieving the obstruction,
      complications and clinical outcome were analysed. RESULTS: Ninety-nine patients
      had malignant disease and in three patients a benign cause of obstruction was
      demonstrated. All procedures were performed during normal working hours. Stenting
      was technically successful in 87 patients (85%). A single stent was placed in 80
      patients. Seven patients required two stents. Of the successful cases, 67 had
      stents placed by fluoroscopy alone and 20 by a combined fluoroscopy/endoscopy
      procedure. Four percent had early complications (within 30 days) which included
      four perforations. There were late complications (over 30 days) in 9% which
      included five stent migrations, two blocked stents and one colovesical fistula.
      Ninety percent (n=76) of the successful patients needed no further radiological
      or surgical intervention later. Survival ranged from 14 days to 2 years.
      CONCLUSION: Colorectal stenting when technically successful is an effective
      procedure for both preoperative and palliative decompression of colonic
      obstruction.

PMID- 16806784
TI  - Shift in imaging modalities of the spine through 25 years and its impact on
      patient ionizing radiation doses.
AB  - STUDY DESIGN: Retrospective. OBJECTIVE: To explore the shift in modalities when
      diagnosing the spine in the years 1979-2003. To see how this shift, together with
      a radiation protective policy, have influenced on the ionizing radiation doses.
      SUMMARY OF BACKGROUND DATA: The shift from CT/myelography to MR when diagnosing
      the spine is well known. To what extent this has changed the radiation doses has
      to our knowledge not yet been published. METHODS: Activity reports from a
      department of radiology have been reviewed. Relevant radiation doses estimates
      have been obtained from the Norwegian Radiation Protection Authority. RESULTS:
      MRI was introduced in 1992 and has been used increasingly since then.
      Conventional X-ray to the spine has been practically unchanged. Myelography and
      CT decreased markedly after the introduction of MRI. The total number of
      examinations of the spine has increased, but the radiation doses given have
      decreased since 1993. CONCLUSIONS: The introduction of MRI together with a
      radiation protective policy have reduced the ionizing radiation doses given to
      this population, in spite of an increase in the total number of examinations of
      the spine.

PMID- 16806785
TI  - The management of emergency radiology: key facts.
AB  - Diagnostic imaging is very important in the diagnosis and management of the
      emergency patient. It is necessary for the emergency radiology unit to be located
      within the Emergency Department, and to allow the interdisciplinary management of
      the patient by all specialists. Logistics, technological equipment and staff of
      the emergency radiology unit must be designed and worked out in the best way to
      guarantee the fastest and effective assistance to the emergency patient.

PMID- 16806786
TI  - Diastereoisomeric resolution of a pronucleotide using solid phase extraction and
      high performance liquid chromatography: application to a stereoselective
      decomposition kinetic in cell extracts.
AB  - A stereospecific HPLC methodology has been developed for the diastereoisomeric
      resolution of a mononucleotide prodrug in cell extracts. This method involves the
      use of solid phase extraction on a C18 cartridge. Diastereoisomers and internal
      standard resolutions were performed on a cellulose based chiral column (Chiralcel
      OD-H) used in the normal phase mode. The method was validated in terms of
      specificity, recovery, linearity (diasteroisomers mixture concentration: 3-60
      micromol L(-1)), precision and accuracy and detection limit (1.67 and 1.33
      micromol L(-1) for first and second eluted diastereoisomer). This method was
      applied to the determination of the apparent rate constants of disappearance and
      half-lives of each stereoisomers. This permits to conclude to the
      stereoselectivity of the enzymatic activity involved in the decomposition pathway
      of 2.

PMID- 16806787
TI  - LC-MS Determination of remifentanil in maternal and neonatal plasma.
AB  - An HPLC-MS with electrospray ionization method for the determination of
      remifentanil in human plasma samples, pre-treated with SPE cartridge, has been
      developed and validated. Ionisation was performed by positive-ion electrospray
      and quadrupole filter mass spectrometer operated in the single ion-recording
      mode. Pre-treatment was performed using Waters Oasis((R)) SPE cartridges.
      Chromatographic separation was achieved in isocratic elution using a X-Terra C8 5
      microm, 150 mm x 2.1 mm i.d. column. The mobile phase consisted of a mixture of
      water, methanol and acetonitrile (86:10:4, v/v/v) containing 0.1% of formic acid.
      The method showed to be linear in the range between 0.5 and 48.0 ng/ml, the
      estimated LOD is 0.18 ng/ml and the LOQ is 0.5 ng/ml. The method can be used to
      quantify remifentanil in plasma samples taken from adult and newborn patients in
      a range suitable for clinical studies.

PMID- 16806788
TI  - Behavioral and hypothalamic-pituitary-adrenal responses to anterodorsal thalami
      nuclei lesions and variable chronic stress in maternally separated rats.
AB  - In maternally separated rats, variable chronic stress decreased the emotional
      reactivity and provoked a state of hypoactivity of the hypothalamic-pituitary
      adrenal system at 3 months old but increased its activity after the open field
      test. The anterodorsal thalami nuclei control of the endocrine response under
      stress conditions was not manifested however its seems activate grooming
      behavior. The development of behavioral and endocrine response to stress is
      influenced by early postnatal environment. On the other hand, the anterodorsal
      thalami nuclei exert an inhibitory influence on the hypothalamic-pituitary
      adrenal system under basal and stressful conditions. The aim of this work is to
      determine the magnitude of behavioral and hypothalamic-pituitary-adrenal
      responses to variable chronic stress in adult female rats with anterodorsal
      thalami nuclei lesions, previously isolated for 4.5 h daily during the first 3
      weeks of life. The groups were: non-maternally separated sham and lesioned,
      maternally separated sham and lesioned with variable chronic stress with and
      without open field test. At 3 months old, under variable chronic stress, maternal
      separation provoked an increase in ambulation in sham and lesioned animals
      (P<0.01) but this parameter was not modified by lesion in either non-maternally
      separated or maternally separated groups. Neither the lesion nor the maternal
      separation changed the defecation and rearing parameter. Grooming behavior was
      lower in maternally separated lesioned rats (P<0.05). Under variable chronic
      stress maternal separation decreased adrenocorticotrophin hormone in comparison
      with non-maternally separated (P<0.001) and the lesion did not alter this
      response. Regarding corticosterone concentrations, maternal separation did not
      affect this hormone under variable chronic stress conditions and after the open
      field test there was an increase of this in both non-maternally separated and
      maternally separated sham and lesioned (P<0.001).

PMID- 16806789
TI  - Differential effects of hypoglossal and facial nerve injuries on survival and
      growth of rats at different developmental stages.
AB  - The hypoglossal (XII) nerve is made up of functionally different nerve branches:
      the medial branch related to protrusion of the tongue and the lateral branch
      related to its retraction. The present study was performed to determine the
      effects of facial (VII) and XII nerve injuries on the survival and growth of rats
      in which the unilateral or bilateral VII and XII nerve components (main trunk,
      XII-trunk; medial branch, XII-med; lateral branch, XII-lat) had been resected at
      different developmental stages. In the suckling period, unilateral as well as
      bilateral injuries in the XII-trunk or XII-med nerve produced disturbed milk
      intake, lower survival rates and growth retardation in the nerve-injured rats. In
      the transition and mastication periods, only bilateral injury in the XII-trunk or
      XII-med nerve produced disturbed food intake followed by lower survival rates and
      growth retardation in those animals. The unilateral XII-lat nerve injury did not
      have significant effects on milk and food intake, whereas the bilateral injury
      caused disturbance in milk intake especially at the early neonatal stage. The
      unilateral VII nerve injury at the early neonatal stage caused deteriorating
      effects on food intake resulting in lower survival rate and severe growth
      retardation in the nerve-injured rats. The results indicate that the survival and
      growth of XII and VII nerve-resected rats differ considerably depending on the
      nerves injured and the developmental ages of the animals at the time of nerve
      insult.

PMID- 16806790
TI  - Differences between primiparous and multiparous dairy cows in the inter
      relationships between metabolic traits, milk yield and body condition score in
      the periparturient period.
AB  - During the early postpartum period dairy cows mobilize fat and muscle to support
      lactation. This is associated with alterations in blood metabolite and hormone
      profiles which in turn influence milk yield and fertility. This study developed
      models to determine how metabolic traits, milk yield and body condition score
      were inter-related at different times in the periparturient period and to compare
      these relationships in primiparous (PP, n=188) and multiparous (MP, n=312) cows.
      Data from four previous studies which included information on blood metabolic
      parameters, parity, milk yield, body condition score and diet were collated into
      a single dataset. Coefficients of polynomial equations were calculated for each
      trait between -1 week pre-calving and week +7 postpartum using residual maximum
      likelihood modelling. The completed dataset was used in a multiple correlation
      model to determine how the best fit curves were related to each other over time.
      PP cows had higher concentrations of insulin-like growth factor-I and lower beta
      hydroxybutyrate concentrations throughout, higher leptin concentrations pre
      partum and both the peak in non-esterified fatty acids and the nadir in urea
      concentration occurred earlier after calving. These differences were associated
      with significantly lower milk production. Leptin concentrations fell at calving
      and were related to body condition score. Insulin was negatively correlated with
      yield in MP cows only. In MP cows the relationship between insulin-like growth
      factor-I and yield switched from negative to positive between weeks +4 and +7.
      Both beta-hydroxybutyrate and urea were positively related to yield in PP cows.
      In contrast, in MP cows beta-hydroxybutyrate was negatively correlated with yield
      and urea was strongly related to body condition score but not yield. These
      results suggest that there are differences in the control of tissue mobilization
      between PP and MP cows which may promote nutrient partitioning into growth as
      well as milk during the first lactation.

PMID- 16806791
TI  - Cloning and characterization of canine thyroglobulin complementary DNA.
AB  - Canine thyroglobulin (cTg) is one of the thyroid autoantigens associated with
      hypothyroidism caused by autoimmune thyroiditis in dog. To identify canine
      specific areas in cTg, we cloned, by reverse transcriptase PCR, and sequenced the
      complete cDNA of cTg. It revealed an open reading frame of 8289 nucleotides,
      which encode a polypeptide of 2762 amino acids that is 78.9 and 78.1% identical
      to bovine and human thyroglobulin, respectively. This complete cTg sequence may
      be useful to promote the understanding of the primary structure of cTg and, it
      will be informative data in the further search about antigenic epitopes
      associated with autoimmune thyroiditis and pathogenesis of cTg-associated thyroid
      diseases in dog.

PMID- 16806792
TI  - Overexpression of RhoA is associated with poor prognosis in hepatocellular
      carcinoma.
AB  - AIMS: The aim of this study was to investigate the relationship between RhoA
      expression and clinic pathological parameters of hepatocellular carcinoma (HCC),
      and to evaluate the prognostic value of RhoA for HCC patients. METHODS: Three
      methods, including reverse transcription and polymerase chain reaction, Western
      blot and immunohistochemical staining were employed to detect RhoA expression in
      128 HCC specimens. The correlation between RhoA expression and clinicopathologic
      outcome, and prognostic value of RhoA for HCC patients were analyzed. RESULTS:
      HCC tissues revealed significantly higher levels of both RhoA mRNA and protein
      than pericarcinomatous liver tissues (PCLT) (P=0.001). The mRNA and protein
      expression levels of RhoA in HCC tissues showed strongly positive correlation
      (correlation coefficient=0.712, P=0.01). There was significant correlation among
      RhoA mRNA and protein overexpression, and venous invasion (P=0.009 and P=0.040,
      respectively) and cell differentiation (P=0.021 and P=0.017). HCC patients with
      RhoA-positive expression showed a significantly poor prognosis than those with
      RhoA-negative expression (P=0.039). CONCLUSIONS: Our data strongly suggested that
      increased RhoA expression in HCC correlated with venous invasion and cell
      differentiation of HCC, overexpression of RhoA indicated a poor prognosis in HCC
      patients.

PMID- 16806793
TI  - Experience with intradermal injection and intradermal-plus-deep injection in the
      radioguided sentinel node biopsy of early breast cancer patients.
AB  - AIMS: Methods of administering (99m)Tc-phytate during sentinel node biopsy of
      early breast cancer patients were compared to improve the sensitivity of the
      technique. METHODS: Two injection methods, intradermal vs. intradermal-plus-deep
      injection, were compared in 648 early breast cancer patients. Intradermal
      injection was done in 323 consecutive patients (325 breasts), and intradermal
      plus-deep injection was done in 325 consecutive patients (329 breasts). The
      following items were compared: (1) The number of axillary nodes detected
      scintigraphically and removed surgically, and the breast number of
      micrometastasis to axillary nodes; (2) The number of internal mammary nodes
      detected scintigraphically and removed surgically; and (3) The sensitivity of
      axillary SNB. RESULTS: The number of axillary nodes scintigraphically detected
      was 1.63+/-0.80 (mean+/-SD) in patients given intradermal injection, and was
      1.82+/-0.94 in patients given intradermal-plus-deep injection. The number of
      axillary nodes surgically removed was 1.78+/-0.93 in patients given intradermal
      injection, and was 1.95+/-0.99 in patients given intradermal-plus-deep injection.
      The visualization of internal mammary nodes was superior with intradermal-plus
      deep injection (5/325 for intradermal, and 51/329 for intradermal-plus-deep). The
      putative sensitivity was 71/72 (98.6%) for the intradermal-plus-deep method and
      56/62 (90.3%) for the intradermal method. The frequency of detection of
      micrometastasis was 24 in 71 true positive (38.8%) for the intradermal-plus-deep
      method and 13 in 56 true positive (23.2%) for the intradermal method.
      CONCLUSIONS: The SNB procedure with the intradermal-plus-deep injection method
      detected more axillary and internal mammary nodes, more (not statistically
      significant) micrometastasis and improved the putative sensitivity more than the
      SNB procedure with the intradermal injection method.

PMID- 16806794
TI  - Morbidity after inguinal sentinel lymph node biopsy and completion lymph node
      dissection in patients with cutaneous melanoma.
AB  - BACKGROUND: Aim of the study was to assess the short-term and long-term morbidity
      after inguinal sentinel lymph node biopsy (SLNB) with or without completion groin
      dissection (GD) in patients with cutaneous melanoma. METHODS: Between 1995 and
      2003, 127 inguinal SLNBs were performed for cutaneous melanoma. Sixty-six
      patients, median age 50 (18-77) years, met the inclusion criteria and were
      studied. Short-term complications were analysed retrospectively, while long-term
      complications were evaluated using volume measurement and range of motion
      measurement of the lower extremities. RESULTS: Fifty-two patients underwent SLNB
      alone (SLNB group) and 14 patients underwent completion groin dissection after
      tumour-positive SLNB (SLNB/GD group). Morbidity after SLNB alone: wound
      infections (n=1), seroma (n=1), postoperative bleeding (n=1), erysipelas (n=1),
      and slight lymphedema 6% (n=3). Morbidity after SLNB/GD: wound infections (n=4),
      seroma (n=1), wound necrosis (n=1), postoperative bleeding (n=1), and slight
      lymphedema 64% (n=9). There were differences between the two groups in the total
      number of short-term complications (p<0.001), volume difference (p<0.001),
      flexion (p=0.009), and abduction (p=0.011) limitation of the hip joint.
      CONCLUSION: Inguinal SLNB is accompanied with a low complication rate. However,
      SLNB followed by groin dissection is associated with an increased risk of wound
      infection and slight lymphedema.

PMID- 16806795
TI  - Reconstruction of large defects on the scalp and forehead as an interdisciplinary
      challenge: experience in the management of 39 cases.
AB  - AIMS: To describe options and indications for different surgical reconstruction
      techniques after resection of large skin tumours on the scalp taking into account
      an interdisciplinary approach of cranio-maxillofacial surgeon, dermatologist, and
      neurosurgeon, and to evaluate complications and postoperative outcome. PATIENTS
      AND METHODS: From a total of 39 patients with large skin tumour resections on the
      scalp and/or the forehead, treated between January 01, 1995 and June 30, 2005, a
      number of 42 surgical reconstructions were performed. The medical histories, the
      surgical treatment, postoperative complications, follow-up and outcome were
      evaluated. RESULTS: The excision defects measured 146 cm(2) (range: 80.6-546
      cm(2)) on average. The most common methods for defect closure were multiple
      rotation-advancement flaps (n=19). Six patients were treated with split-thickness
      skin grafts after bone drilling for inducing granulation tissue to grow. Free
      latissimus dorsi muscle flaps were used in 8 patients and radial forearm flaps in
      4 cases. Postoperative complications were rare. An algorithm for the surgical
      approach to large scalp defects was developed. CONCLUSION: For reconstruction of
      large defects on the scalp and forehead, various reliable methods may be used
      with regard to individual patient-specific parameters in cooperation with
      different medical specialties involved.

PMID- 16806796
TI  - Significance of lymph node metastasis in patients with diffuse malignant
      peritoneal mesothelioma.
AB  - BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and
      invariably fatal neoplasm. Some studies have shown that cytoreductive surgery
      (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) achieved an
      improved survival, as compared to historical controls. However, the significance
      of lymph node involvement in this disease has never been well defined. METHODS:
      One hundred patients with DMPM underwent CRS and PIC at the Washington Hospital
      Center. The inclusion criteria for surgery consisted of histological diagnosis of
      DMPM, age <80 years and good performance status. All data were collected
      prospectively. Lymph node status, seven clinical variables and eight treatment
      related prognostic factors were analyzed for survival. RESULTS: Seven patients
      were lymph node positive and they all died of their disease within 2 years after
      the surgery. The remaining 93 patients had 5- and 7-year survival of 50% and 43%,
      respectively. Univariate analysis showed that gender (p<0.001), peritoneal cancer
      index (p=0.009), lymph node status (p<0.001), extra-abdominal invasion (p=0.026),
      histological type (p<0.001), intraoperative blood loss (p=0.035), completeness of
      cytoreduction (p<0.001), intraperitoneal chemotherapy regimen (p=0.041), and redo
      cytoreductive surgery (p=0.022) were significant for survival. Multivariate
      analysis demonstrated that female gender, lymph node metastasis not detected,
      epithelial type, and adequate cytoreduction were independently associated with an
      improved survival. CONCLUSIONS: CRS and PIC showed an improved survival for DMPM,
      as compared to historical controls. Lymph node status along with three other
      prognostic variables was significant in the multivariate analysis.

PMID- 16806797
TI  - Increases in circulating VEGF levels during COX-2 inhibitor treatment in breast
      cancer patients.
AB  - Cyclooxygenase-2 (COX-2) inhibitors are being tried in clinics for cancer
      treatment. One of the mechanism by which COX-2 inhibitors suppress cancer
      progression is suggested to be inhibition of angiogenesis. To investigate how COX
      2 inhibitors affect regulation of angiogenic factors, we studied alterations in
      VEGF levels in sera and plasma during COX-2 inhibitor treatment in breast cancer
      patients. Serum and plasma VEGF levels were monitored in 48 patients treated with
      the COX-2 inhibitor celecoxib together with 5-FU, epirubicine, cyclophosphamide
      (FEC). Serum VEGF levels showed decreases on day 3 of the first cycle (P<0.0001),
      followed by increases after 3 weeks (P<0.0001). Plasma VEGF levels did not show
      decreases on day 3 but showed increases after 3 weeks (P<0.05). The increases of
      VEGF levels in sera and plasma continued until the next cycle of the treatment.
      In patients treated with FEC alone (without celecoxib) did not show increases in
      serum VEGF levels during the treatment. Our data showed that treatment with COX-2
      inhibitors decreased serum VEGF levels at an early time and increased VEGF levels
      in serum and plasma at a late time in breast cancer patients. Further studies are
      necessary to elucidate how COX-2 inhibitors regulate production of VEGF in
      different cells and different tissues in cancer patients.

PMID- 16806798
TI  - Identification of a respiratory-type nitrate reductase and its role for survival
      of Mycobacterium smegmatis in Wayne model.
AB  - Nitrate reductase (NR) is found to be expressed in certain mycobacterium sp.
      whose link with the development of persistence is yet to be resolved. The present
      study demonstrates the action of selective inhibitors on NR as well as in the
      survival of Mycobacterium smegmatis using Wayne's model. During gradual shift
      down to anaerobic stage in Wayne's model, conversion of nitrate to nitrite became
      apparent in M. smegmatis. More than 97 percent inhibition was observed for the
      conversion of nitrate to nitrite by azide (0.05 mM) and thiocyanate (20 mM) in
      both whole-cell as well as its cell-free lysate, respectively. Under identical
      condition, chlorate (20 mM) inhibited nitrate reduction by 67 and 10 percent,
      respectively. At these concentrations, neither of azide, thiocyanate nor chlorate
      had any significant effect on cell growth under aerobic condition. In Wayne's
      culture model, thiocyanate and chlorate inhibited the growth of M. smegmatis by
      almost 2 logs at the same concentrations whereas azide inhibited by almost 1.75
      log when added at the time of inoculation. Exposure of same culture at 96 h after
      inoculation in Wayne's model to these inhibitors showed 1.74, 1.95 and 2.37 log
      inhibition of viable cells with respect to azide, thiocyanate and chlorate. These
      findings further indicated that NR inhibitors kill the bacilli at anaerobic stage
      under the experimental condition mentioned. Metronidazole (MTZ) (2 mM) and
      Nitrofurantoin (NIT) (0.3 mM) reduced the cell number at both stages by <0.7 log.
      They did not have any effect on NR. Altogether, the results clearly indicate that
      NR-specific inhibitors could become more promising in killing the bacilli at
      anaerobic stage than the available conventional drugs.

PMID- 16806799
TI  - Effects of seawater salinity fluctuations on primary tissue culture from the
      mussel Mytilus galloprovincialis. Potential application to the detection of
      seawater genotoxicity.
AB  - The present results were obtained in the context of an attempt to develop an in
      vitro test intended to assess the genotoxicity of seawater. It is based on a
      short-term culture method of mussel mantle explants that gives mitotic cells in
      which DNA damage is likely to be detected. Its principle consists of the
      incorporation of the seawater to be tested in the culture medium. Two factors
      that influence cell proliferation were studied: (1) salinity of seawater and (2)
      basic composition of the culture medium i.e. replacement of Eagle's Basal Medium
      (BME) by Eagle's Minimum Essential Medium (MEM). When culture medium contained
      BME, a salinity change from 35 per thousand to 28 per thousand (that is the case
      for coastal or estuarine waters) resulted in a significant reduction of cell
      proliferation. In contrast, when culture medium was prepared with MEM, the same
      decrease of salinity did not change significantly the number of metaphase cells
      obtained. This suggested medium prepared with MEM allowed tissues in culture to
      better withstand the hypoosmotic shock generated by 28 per thousand seawater.
      This has been attributed to amino acids the concentration of which being higher
      in MEM than in BME. Direct and indirect mechanisms of osmoregulation are
      suggested to explain the observations. These results show that the test proposed
      could be used to assess the genotoxicity of coastal or estuarine seawater with
      salinity comprised from 28 per thousand to 35 per thousand, provided that MEM is
      used.

PMID- 16806800
TI  - The cognitive mediation of obsessive-compulsive symptoms: a longitudinal study.
AB  - Contemporary cognitive models of obsessive-compulsive disorder (OCD) posit that
      OC symptoms arise from negative interpretations of intrusive thoughts, which are
      derived from trait-like dysfunctional assumptions ("obsessive beliefs;" e.g.,
      concerning overestimates of responsibility). Although correlational studies
      suggest that obsessive beliefs, negative interpretations of intrusions, and OC
      symptoms are interrelated, prospective studies evaluating the directional
      hypotheses implied in the cognitive model are lacking. In the present
      longitudinal study, 76 first time expecting parents were followed through the
      postpartum. Results indicated that the tendency to negatively interpret the
      presence and meaning of unwanted intrusive infant-related thoughts early in the
      postpartum period (3-4 weeks) mediated the relationship between pre-childbirth
      obsessive-beliefs and late postpartum (12 weeks) OC symptoms. Results are
      discussed in terms of their theoretical and treatment implications.

PMID- 16806801
TI  - Examination of the decline in fear and disgust during exposure to threat-relevant
      stimuli in blood-injection-injury phobia.
AB  - In the present study, participants (N=22) displaying marked fear of blood
      injection-injury (BII) stimuli were provided 30 min of in vivo exposure to threat
      relevant stimuli, during which time their fear and disgust levels were repeatedly
      assessed. Growth curve analyses were then conducted to examine the decay slopes
      in both fear and disgust and their relationship. Results indicated that exposure
      led to significant declines in fear and disgust across trials. However, the decay
      slope observed for fear was significantly greater than that for disgust. Further
      analyses revealed that the decline in fear across trials remained significant
      after accounting for the changes in disgust. However, the effect of trial on
      disgust was no longer significant after controlling for the reduction in fear.
      Global disgust sensitivity levels prior to exposure did not moderate the level of
      fear activation or fear reduction during exposure. BII-specific digust
      sensitivity was also not associated with initial levels of fear. However, levels
      of BII-specific disgust sensitivity were independently negatively associated with
      fear decline. Theoretical and clinical implications of the findings are
      discussed.

PMID- 16806802
TI  - Subtypes of social phobia: are they of any use?
AB  - This study investigated the existence of DSM-IV social phobia subtype models in
      the community. Data came from the Dresden Predictor Study of a representative
      sample of 1877 German women (aged 18-24 years) who completed a diagnostic
      interview and filled out various self-report questionnaires. The number of feared
      social situations was distributed continuously without a clear-cut for
      delineation of subtypes and significantly increased functional impairment,
      comorbidity, subjective need for psychotherapy, seeking psychotherapeutic help
      and dysfunctional attitudes, and decreased social support and mental health.
      Subtype models based on the number (1, 2-4 and >4) and type ('formal speaking
      fear' versus 'other fears') of social fear did not have extra value above the
      continuum model of social phobia. The heterogeneity within social phobia has to
      be seen as a continuum of severity of social phobia, with a greater number of
      feared situations associated with more functional, social and psychological
      disability.

PMID- 16806803
TI  - Across-tissue expression and evolution of genes controlled by the Aire
      transcription factor.
AB  - Aire (autoimmune regulatory protein) enhances expression of certain genes in
      thymic medullary epithelial cells (MECs). Using publicly available data, we
      examined expression patterns, across 82 distinct tissue types, of genes
      previously identified as Aire-activated, Aire-repressed, and Aire-independent.
      Consistent with the hypothesis that the effect of Aire in MECs is to increase
      expression of tissue-specific genes, Aire-activated genes had a low overall level
      of expression but a large range between the lowest and the highest levels of
      expression in different tissues. By contrast, Aire-repressed genes tended to have
      a high overall level of expression and less marked differences between the
      highest and the lowest levels of expression. Nonetheless, the expression scores
      of Aire-repressed genes showed broader ranges of values than those of Aire
      independent genes. Phylogenetic analyses of members of two gene families that
      included two Aire-activated genes illustrated two contrasting patterns of the
      relationship of Aire-activated genes within the same family. The two Aire
      activated members of the major urinary protein family arose through a recent gene
      duplication (after the rat-mouse divergence), whereas the most recent common
      ancestor of the two Aire-activated members of cytochrome p450 family 2 duplicated
      prior to the radiation of the eutherian orders. In the latter family, the Aire
      activated Cyp2a4 gene and the Aire-independent Cyp2a5 gene arose through a recent
      duplication, after the rat-mouse divergence. Thus the set of Aire-activated genes
      is subject to change over evolutionary time and includes genes of recent origin.

PMID- 16806804
TI  - Interactions among genomic structure, function, and evolution revealed by
      comprehensive analysis of the Arabidopsis thaliana genome.
AB  - The genome in a higher organism consists of a number of types of nucleotide
      sequence-specialized components, with each having tens of thousands of members or
      elements. It is crucial for our understanding of how a genome as an entity is
      organized, functions, and evolves to determine how these components are organized
      in the genome and how they relate with each other; however, no such knowledge is
      available. Here, we report a comprehensive analysis of the organization and
      interaction of all 40 components constituting the genome of the plant model
      species, Arabidopsis thaliana, at the whole-genome and chromosome levels. The 40
      components include (i) 6 genome structural components consisting of GC%, genes,
      retrotransposons, DNA transposons, simple repeats, and low complex repeats; (ii)
      3 evolutionarily critical features consisting of recombination rate, nucleotide
      substitutions, and nucleotide insertions/deletions; and (iii) 31 categories of
      genes with different functions and numbers of functions. We show that the
      distributions of 39 of the 40 components of the genome (excepting GC%) deviate
      significantly from the random distribution model and different types of the
      genome components are significantly correlated. These results remained to be true
      even when the genomic regions, such as centromeric regions, where transposable
      and repeat elements are abundant were excluded from the analyses. These findings
      suggest that DNA molecules contained in the Arabidopsis genome are each organized
      and structured from their constituting components in an unambiguous manner and
      that different types of the components that constitute or characterize the genome
      interact. The analysis also showed that each chromosome consists of a similar set
      of the components at similar densities, suggesting that the unique organization
      and interaction pattern of the components in each chromosome may represent, at
      least in part, the identity of a chromosome or a genome at the genome level, thus
      partly accounting for the phenotypic variation among different species. The data
      also provide comprehensive and new insights into many phenomena significant in
      genome biology, with which we particularly discuss the variation of genetic
      recombination. The variation of genetic recombination rate along a chromosomal
      arm is shaped, not only by the distribution of simple repeats, retrotransposons,
      DNA transposons, and nucleotide substitutions, but also by the functions of genes
      contained, especially those with multiple functions, suggesting that variation of
      genetic recombination along a chromosomal arm is the result of interactions among
      the components constituting local genome structure, function, and evolution.

PMID- 16806805
TI  - Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired
      dachshunds as a homologue of human Leber congenital amaurosis.
AB  - Cone-rod dystrophy 1 (cord1) is a recessive condition that occurs naturally in
      miniature longhaired dachshunds (MLHDs). We mapped the cord1 locus to a region of
      canine chromosome CFA15 that is syntenic with a region of human chromosome 14
      (HSA14q11.2) containing the retinitis pigmentosa GTPase regulator-interacting
      protein 1 (RPGRIP1) gene. Mutations in RPGRIP1 have been shown to cause Leber
      congenital amaurosis, a group of retinal dystrophies that represent the most
      common genetic causes of congenital visual impairment in infants and children.
      Using the newly available canine genome sequence we sequenced RPGRIP1 in affected
      and carrier MLHDs and identified a 44-nucleotide insertion in exon 2 that alters
      the reading frame and introduces a premature stop codon. All affected and carrier
      dogs within an extended inbred pedigree were homozygous and heterozygous,
      respectively, for the mutation. We conclude the mutation is responsible for cord1
      and demonstrate that this canine disease is a valuable model for exploring
      disease mechanisms and potential therapies for human Leber congenital amaurosis.

PMID- 16806806
TI  - Prenatal developmental toxicity study of the basic rubber accelerator, 1,3-di-o
      tolylguanidine, in rats.
AB  - Pregnant rats were given 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 10, 20 or
      40 mg/kg bw/day on days 6-19 of pregnancy and the pregnancy outcome was
      determined on day 20 of pregnancy. At 40 mg/kg bw/day, deaths were observed in
      four out of 24 females. The incidences of females showing mydriasis at 20 and 40
      mg/kg bw/day and showing decreased locomotor activity at 40 mg/kg bw/day were
      significantly increased. Alopecia, bradypnea, prone position and tremor were also
      observed at mg/kg bw/day. The maternal body weight gain at 20 and 40 mg/kg bw/day
      and food consumption at 40 mg/kg bw/day were significantly reduced. A
      significantly decreased weight of the gravid uterus, increased incidence of
      postimplantation loss, decreased number of live fetuses, and lowered weights of
      fetuses and placentae were found at 40 mg/kg bw/day. The incidences of the total
      number of fetuses with external malformations at 40 mg/kg bw/day and with
      skeletal malformations at 20 and 40 mg/kg bw/day were significantly increased.
      Significantly higher incidences of fetuses with brachydactyly and short tail and
      defects of caudal vertebrae, phalanges and metacarpals were observed at 40 mg/kg
      bw/day. Delayed ossification was also noted at 40 mg/kg bw/day. The data indicate
      that DTG is teratogenic at maternal toxic doses and the NOAELs of DTG for
      maternal and developmental toxicity are 10 mg/kg bw/day in rats.

PMID- 16806807
TI  - Genetic causes of male infertility.
AB  - Genetic causes account for 10-15% of severe male infertility, including
      chromosomal aberrations and single gene mutations. Natural selection prevents the
      transmission of mutations causing infertility, while this protective mechanism
      may be overcome by assisted reproduction techniques. Consequently the
      identification of genetic factors has become good practice for appropriate
      management of the infertile couple. Furthermore, patients affected by some forms
      of genetic alterations produce a higher frequency of sperm with aneuploidies.
      Sperm aneuploidies are the direct result of the constitutional genetic
      abnormality or are caused by meiotic errors induced by the altered testicular
      environment that these men present. In this review we will report and discuss the
      genetic causes of male infertility known up to date and we will analyse genetic
      polymorphisms possibly associated with male infertility.

PMID- 16806808
TI  - Nicotine downregulates the l-selectin system that mediates cytotrophoblast
      emigration from cell columns and attachment to the uterine wall.
AB  - Here we show that maternal smoking downregulated, in a dose-dependent manner,
      cytotrophoblast expression of l-selectin and its TRA-1-81-reactive carbohydrate
      ligands. Cell islands -- cell columns that fail to make uterine attachments,
      often more numerous in the placentas of smokers -- exhibited an even greater
      downregulation of the l-selectin adhesion system. These effects were attributable
      to nicotine, since exposure of explanted villi to this drug in vitro reproduced
      the effects observed in situ. Videomicroscopy showed that the downstream
      consequences included inhibition of all stages of cytotrophoblast outgrowth from
      columns, including rolling adhesion within columns and generation of invasive
      cells at the distal ends. These results suggest that nicotine, acting through the
      l-selectin adhesion system, impairs the development of cell columns that connect
      the fetal portion of the placenta to the uterus, one possible reason why women
      who smoke have a much harder time achieving and sustaining pregnancy than their
      nonsmoking counterparts.

PMID- 16806809
TI  - PCR approach for the detection of Trypanosoma brucei and T. equiperdum and their
      differentiation from T. evansi based on maxicircle kinetoplast DNA.
AB  - The goal of this study was to develop a PCR approach based on the sequence of
      maxicircle kinetoplast DNA (kDNA) of Trypanosoma brucei to distinguish T.
      brucei/T. equiperdum from T. evansi and to evaluate its diagnostic use for their
      detection in blood samples. Primers derived from the sequence of the maxicircle
      kDNA of T. brucei, encoding the NADH dehydrogenase subunit 5 (nad5) gene, were
      used to test the PCR-amplification from T. brucei (including T. b. brucei and T.
      b. rhodesiense), T. equiperdum, T. evansi, T. vivax and T. congolense. A primer
      pair to a nuclear DNA region incorporated into a separate PCR was employed to
      control for the presence of amplifiable genomic DNA (representing the subgenus
      Trypanozoon) in each sample subjected to the PCR. Products of approximately 395bp
      were amplified from all T. brucei and T. equiperdum samples tested using the nad5
      PCR, but not from T. evansi DNA samples or any of the control samples
      representing T. vivax, T. congolense, or host. The current PCR approach allows
      the rapid differentiation of T. brucei/T.equiperdum from T. evansi and can detect
      the equivalent of 20-25 cells of T. brucei or T. equiperdum in purified genomic
      DNA or infected blood samples.

PMID- 16806810
TI  - Potential regulatory SNPs in promoters of human genes: a systematic approach.
AB  - Single nucleotide polymorphisms (SNPs) can significantly contribute to the
      cellular level of the mRNA transcripts encoded by human disease related genes.
      DNA variations between individuals can be an indication of predisposition to
      disease or affect the response to treatment. An algorithm allowing in silico
      extraction of SNPs with the high probability of influencing the level of gene
      expression is highly desirable. We performed a whole-genome analysis of SNP
      markers in regulatory areas of the human genes. Computational criteria were
      applied to predict an influence of the nucleotide replacement on the individual
      gene's expression. We formed a list of 14127 regulatory SNPs corresponding to
      8555 regulatory areas suitable for future association studies. A catalogue of
      1859 SNP entries, confirmed by analysis in populations, and allocated to 1607
      human regulatory areas was created. We also revealed 13 cases of overlapped
      promoters corresponding to the human genes transcribed from opposite DNA strands
      and containing the regulatory SNP markers validated in populations. A population
      validated set of regulatory SNP markers is organized in a database available in
      open access as a Supplementary file and by ftp://194.67.85.195/.

PMID- 16806811
TI  - Distribution of orexin/hypocretin immunoreactivity in the brain of a male
      songbird, the house finch, Carpodacus mexicanus.
AB  - Previous research has shown orexin/hypocretin immunoreactive (orexin-ir) neurons
      in domesticated Galliformes. However, these findings may not be representative of
      other birds and these studies did not include a distribution of orexin-ir
      projections throughout the brain. The present study was carried out in a wild
      caught passerine, the house finch, Carpodacus mexicanus, and includes a detailed
      description of orexin-ir neurons and their projections. Orexin A and B-ir neurons
      were located in a single population centered on the paraventricular nucleus of
      the hypothalamus extending into the lateral hypothalamic area, consistent with
      other studies in birds. Orexin A and B-ir fibers were similarly visible across
      the brain, with the highest density within the preoptic area, hypothalamus and
      thalamus. Orexin-ir projections extended from the paraventricular nucleus
      rostrally to the preoptic area, laterally towards the medial striatum,
      nidopallium, and dorsally along the lateral ventricle towards the mesopallium.
      Caudally, the highest densities of orexin-ir fibers were found along the third
      ventricle. The periaqueductal grey, substantia nigra pars compacta and the locus
      coeruleus also showed a high density of orexin-ir fibers. This study showed a
      detailed fiber distribution previously unreported in birds and showed that orexin
      ir neurons were located in similar areas regardless of phylogeny or domestication
      in birds. The apparently conserved neural distribution of orexins suggests that
      these peptides play similar roles among birds. The widespread distribution of the
      projections in brain areas serving various roles indicates the potential
      involvement of these peptides in multiple behavioral and physiological functions.

PMID- 16806812
TI  - Effects of a Snoezelen room on the behavior of three autistic clients.
AB  - The effect of a Snoezelen room on the disruptive and prosocial behavior of three
      male, autistic inpatients was examined. In an ABAB reversal design, specific
      disruptive and prosocial behaviors were recorded for each client throughout the
      four 28-day periods of the study. Results indicated that the three clients had
      different responses to the room, but no client showed a decrease in disruptive
      behaviors while in the Snoezelen condition compared to baseline, and one client
      showed a clear pattern of increased disruptive behavior during the Snoezelen
      periods. There was a slight tendency for clients to engage in more prosocial
      behaviors while in Snoezelen. These findings do not support the contention that
      Snoezelen rooms are effective interventions for aggressive behavior in this
      client population.

PMID- 16806813
TI  - Methanol alters ecto-nucleotidases and acetylcholinesterase in zebrafish brain.
AB  - Methanol is a neurotoxic compound that is responsible for serious damage on CNS.
      Besides being found as an environmental contaminant, this alcohol is also
      employed as a component of cryoprotector solutions for zebrafish embryos. Here we
      tested the acute effect of methanol on ecto-nucleotidase (NTPDase, ecto-5'
      nucleotidase) and acetylcholinesterase (AChE) activities in zebrafish brain.
      After acute treatment, there were significant decreases on ATP (26% and 45%) and
      ADP hydrolysis (26% and 30%) at 0.5% and 1.0%, respectively. However, no
      significant alteration on ecto-5'-nucleotidase activity was verified in zebrafish
      brain. A significant inhibition on AChE activity (39%, 33% and 30%) was observed
      at the range of 0.25% to 1.0% methanol exposure. Four NTPDase sequences were
      identified from phylogenetic analyses, which one is similar to NTPDase1 and the
      others to NTPDase2. Methanol was able to inhibit NTPDase1, two isoforms of
      NTPDase2 and AChE transcripts. To evaluate if methanol affects directly these
      enzymes activities, we have performed in vitro assays. ATP hydrolysis presented a
      significant inhibition (19% and 34%) at 1.5% and 3.0%, respectively, and ADP
      hydrolysis decreased only at 3.0% (29.2%). Nevertheless, AMP hydrolysis and AChE
      were not altered after in vitro exposure. The inhibitory effect observed on these
      enzymes could contribute to the neurodegenerative events promoted by methanol in
      zebrafish brain.

PMID- 16806814
TI  - Associations between platelet monoamine oxidase-B activity and acquired colour
      vision loss in a fish-eating population.
AB  - Platelet monoamine oxidase-B (MAO-B) has been considered a surrogate biochemical
      marker of neurotoxicity, as it may reflect changes in the monoaminergic system in
      the brain. Colour vision discrimination, in part a dopamine dependent process,
      has been used to identify early neurological effects of some environmental and
      industrial neurotoxicants. The objective of this cross-sectional study was to
      explore the relationship between platelet MAO-B activity and acquired colour
      discrimination capacity in fish-consumers from the St. Lawrence River region of
      Canada. Assessment of acquired dyschromatopsia was determined using the Lanthony
      D-15 desaturated panel test. Participants classified with dyschromatopsia (n=81)
      had significantly lower MAO-B activity when compared to those with normal colour
      vision (n=32) (26.5+/-9.6 versus 31.0+/-9.9 nmol/min/20 microg, P=0.030)).
      Similarly, Bowman's Colour Confusion Index (CCI) was inversely correlated with
      MAO-B activity when the vision test was performed with the worst eye only (r=
      0.245, P=0.009), the best eye only (r=-0.188, P=0.048) and with both eyes
      together (r=-0.309, P=0.001). Associations remained significant after adjustment
      for age and gender when both eyes (P=0.003) and the worst eye (P=0.045) were
      tested. Adjustment for heavy smoking weakened the association between MAO-B and
      CCI in the worst eye (P=0.140), but did not alter this association for both eyes
      (P=0.006). Adjustment for blood-mercury concentrations did not change the
      association. This study suggests a relationship between reduced MAO-B activity
      and acquired colour vision loss and both are associated with tobacco smoking.
      Therefore, results show that platelet MAO-B may be used as a surrogate
      biochemical marker of acquired colour vision loss.

PMID- 16806815
TI  - Fine needle aspiration: a novel application in laryngology.
AB  - Fine needle aspiration (FNA) has had an early start in medicine and has been
      heavily used in the United States since the 1980s. It is regarded as a highly
      effective means to sample mass lesions, serving as the first diagnostic procedure
      in many instances. FNA is safe, less invasive than biopsy, and reduces the risk
      of scar formation. Its main limitations can be overcome through effective
      training and practiced technique. In laryngology, the development of new and
      diversified therapeutic and diagnostic strategies depends on the development of
      equally appropriate diagnostic tools. FNA has the potential to be a relatively
      easy procedure that can be performed under local anesthesia, increasing the
      otolaryngologist's armamentarium. Combining the FNA procedure with technology now
      available, secondary to advances in genomic science, rather than cytology and H&E
      stains, provides the means of obtaining clinically useful information about
      benign and malignant disease for clinicians and researchers. This paper provides
      a review of the traditional FNA procedure. It offers an introduction to the
      future applicability of FNA to office-based laryngology. Lastly, this paper
      familiarizes the reader with the genomic principles being used for this
      procedure.

PMID- 16806816
TI  - Acoustic analysis of the interaction of choral arrangements, musical selection,
      and microphone location.
AB  - Acoustic differences were evaluated among three choral arrangements and two
      choral textures recorded at three microphone locations. A choir was recorded when
      singing two musical selections of different choral texture, one homophonic and
      one polyphonic. Both musical selections were sung in three choral arrangements:
      block sectional, sectional-in-columns, and mixed. Microphones were placed at the
      level of the choristers, the conductor, and the audience. The recordings at each
      location were analyzed using long-term average spectrum (LTAS). The LTAS from the
      mixed arrangement exhibited more signal amplitude than the other arrangements in
      the range of 1000-3500Hz. When considering the musical selections, the chorus
      produced more signal amplitude in the region of 1800-2200Hz for the homophonic
      selection. In addition, the LTAS produced by the choir for the homophonic
      selection varied across the microphone locations. As for the microphone location,
      the LTAS of the signal detected directly in front of the chorus had a greater
      slope than the other two locations. Thus, the acoustic signal near the choristers
      differed from the signals near the conductor and in the audience. Conductors may
      be using acoustic information from the region of the second and third formants
      when they decide how to arrange a choir for a particular musical selection.

PMID- 16806817
TI  - Online data visualization using the neural gas network.
AB  - A high-quality distance preserving output representation is provided to the
      neural gas (NG) network. The nonlinear mapping is determined concurrently along
      with the codebook vectors. The adaptation rule for codebook positions in the
      projection space minimizes a cost function that favors the trustworthy
      preservation of the local topology. The proposed visualization method, called OVI
      NG, is an enhancement over curvilinear component analysis (CCA). The results show
      that the mapping quality obtained with OVI-NG outperforms the original CCA, in
      terms of the trustworthiness, continuity, topographic function and topology
      preservation measures.

PMID- 16806818
TI  - Large-scale data exploration with the hierarchically growing hyperbolic SOM.
AB  - We introduce the Hierarchically Growing Hyperbolic Self-Organizing Map (H2SOM)
      featuring two extensions of the HSOM (hyperbolic SOM): (i) a hierarchically
      growing variant that allows for incremental training with an automated adaptation
      of lattice size to achieve a prescribed quantization error and (ii) an
      approximate best match search that utilizes the special structure of the
      hyperbolic lattice to achieve a tremendous speed-up for large map sizes. Using
      the MNIST and the Reuters-21578 database as benchmark datasets, we show that the
      H2SOM yields a highly efficient visualization algorithm that combines the virtues
      of the SOM with extremely rapid training and low quantization and classification
      errors.

PMID- 16806819
TI  - 3D visualization to assist iterative object definition from medical images.
AB  - In medical imaging, many applications require visualization and/or analysis of
      three-dimensional (3D) objects (e.g. organs). At same time, object definition
      often requires considerable user assistance. In this process, objects are usually
      defined in an iterative way and their visualization during the process is very
      important to guide the user's actions for the next iteration. The usual procedure
      provides slice visualization during object definition (segmentation) and 3D
      visualization afterward. In this paper, we propose and evaluate efficient methods
      to provide 3D visualization during iterative object definition. The methods
      combine the differential image foresting transform for segmentation with voxel
      splatting/ray casting for visualization.

PMID- 16806820
TI  - ERK1/2 and p38-MAPK signalling pathways, through MSK1, are involved in NF-kappaB
      transactivation during oxidative stress in skeletal myoblasts.
AB  - Skeletal muscle is highly adapted to respond to oxidative imbalances, since it is
      continuously subjected to an increased production of reactive oxygen species
      (ROS) during exercise. Oxidative stress, however, has been associated with
      skeletal muscle atrophy and damage in many diseases. In this study, we examined
      whether MAPK and NF-kappaB pathways participate in the response of skeletal
      myoblasts to oxidative stress, and whether there is a cross talk between these
      pathways. H(2)O(2) induced a strong activation of ERKs, JNKs and p38-MAPK in a
      time- and dose-dependent profile. ERK and JNK activation by H(2)O(2), but not
      that of p38-MAPK, was mediated by Src kinase and, at least in part, by EGFR.
      H(2)O(2) also stimulated a mild translocation of NF-kappaB to the nucleus, as
      well as a moderate phosphorylation of its endogenous cytoplasmic inhibitor
      IkappaB (at Ser32/36), without any significant decrease in IkappaB total levels.
      Moreover, oxidative stress induced a strong phosphorylation of NF-kappaB p65
      subunit at Ser536 and Ser276. Inhibition of MAPK pathways by selective inhibitors
      did not appear to affect H(2)O(2)-induced nuclear translocation of NF-kappaB or
      the phosphorylation of IkappaB. In contrast, phosphorylation of p65 at Ser276 was
      found to be mediated by MSK1, a substrate of both ERKs and p38-MAPK. In
      conclusion, it seems that, during oxidative stress, NF-kappaB translocation to
      the nucleus is most likely not related with the MAPK activation, while p65
      phosphorylations are in part mediated by MAPKs pathways, probably modifying
      signal specificity.

PMID- 16806821
TI  - Expression of multiple isoforms of the cAMP-dependent protein kinase (PK-A)
      catalytic subunit in the nematode, Caenorhabditis elegans.
AB  - The cAMP-dependent protein kinase (protein kinase A, PK-A) plays a central role
      in the regulation of many aspects of eukaryotic cellular activity. In the free
      living nematode, Caenorhabditis elegans, two genes encode PK-A-like catalytic
      subunits. The kin-1 gene has the potential to generate, through alternative
      splicing events, a multiplicity of catalytic subunit isoforms; in contrast, the
      F47F2.1b gene appears to encode just a single authentic catalytic subunit-like
      protein. Here, we report on the occurrence of, and developmental changes in the
      expression of, polypeptide products of these genes in both C. elegans and the
      closely related nematode, C. briggsae. Polypeptides derived from the F47F2.1 gene
      and its orthologue were detected in mixed stage populations of C. elegans and C.
      briggsae, respectively. Likewise, a number of polypeptides arising as a result of
      alternative splicing of transcripts from kin-1, or its orthologue in C. briggsae,
      were identified in mixed stage populations of nematodes. These isoforms included
      polypeptides with N-termini encoded by exons N'1 or N'4 and C-termini encoded by
      exons 7 or N. The expression of isoforms with an N-terminus encoded by the N'1
      exon is of significance because the amino acid sequence encoded by this exon
      encompasses an N-myristoylation motif. Isoform abundance appears to be related to
      developmental stage. Substantial differences in polypeptide expression profiles
      can be seen in embryonic and adult nematodes. The functional significance of this
      PK-A catalytic subunit isoform diversity is discussed.

PMID- 16806822
TI  - Inhibition of K+ efflux prevents mitochondrial dysfunction, and suppresses
      caspase-3-, apoptosis-inducing factor-, and endonuclease G-mediated constitutive
      apoptosis in human neutrophils.
AB  - Neutrophils die rapidly via apoptosis and their survival is contingent upon
      rescue from constitutive programmed cell death by signals from the
      microenvironment. In these experiments, we investigated whether prevention of
      K(+) efflux could affect the apoptotic machinery in human neutrophils. Disruption
      of the natural K(+) electrochemical gradient suppressed neutrophil apoptosis
      (assessed by annexin V binding, nuclear DNA content and nucleosomal DNA
      fragmentation) and prolonged cell survival within 24-48 h of culture. High
      extracellular K(+) (10-100 mM) did not activate extracellular signal-regulated
      kinase (ERK) and Akt, nor affected phosphorylation of p38 MAPK associated with
      constitutive apoptosis. Consistently, pharmacological blockade of ERK kinase or
      phosphatidylinositol 3-kinase (PI 3-kinase) did not affect the anti-apoptotic
      action of KCl. Inhibition of K(+) efflux effectively reduced, though never
      completely inhibited, decreases in mitochondrial transmembrane potential
      (DeltaPsi(m)) that preceded development of apoptotic morphology. Changes in
      DeltaPsi(m) resulted in attenuation of cytochrome c release from mitochondria
      into the cytosol and decreases in caspase-3 activity. Culture of neutrophils in
      medium containing 80 mM KCl with the pan-caspase inhibitor Z-VAD-FMK resulted in
      slightly greater suppression of apoptosis than KCl alone. High extracellular KCl
      also attenuated translocation of apoptosis-inducing factor (AIF) and endonuclease
      G (EndoG) from mitochondria to nuclei. The DNase inhibitor, aurintricarboxylic
      acid (ATA) partially inhibited nucleosomal DNA fragmentation, and the effects of
      ATA and 80 mM KCl were not additive. These results show that prevention of K(+)
      efflux promotes neutrophil survival by suppressing apoptosis through preventing
      mitochondrial dysfunction and release of the pro-apoptotic proteins cytochrome c,
      AIF and EndoG independent of ERK, PI 3-kinase and p38 MAPK. Thus, K(+) released
      locally from damaged cells may function as a survival signal for neutrophils.

PMID- 16806823
TI  - Galpha13 mediates activation of the cytosolic phospholipase A2alpha through fine
      regulation of ERK phosphorylation.
AB  - Heterotrimeric GTP-binding (G) proteins transduce hormone-induced signals to
      their effector enzymes, which include several phospholipases. In particular, the
      G(o)/G(i) and G(q) protein families have been shown to couple signaling to
      phospholipase A(2) (PLA(2)), phospholipase C, and phospholipase D, while the
      G(12)/G(13) family has been linked to the activation of small GTPases of the Rho
      family, and hence, to phospholipase D activation. Here, we demonstrate that in
      CHO cells, the G(12)/G(13) family is also able to activate cPLA(2)alpha, through
      the activation of RhoA and, subsequently, ERK1/2. Hormone-induced arachidonic
      acid release increased as a consequence of Galpha(13) overexpression, and was
      inhibited through inhibition of Galpha(13) signaling. The Galpha(13)-mediated
      cPLA(2)alpha activation was inhibited by pharmacological blockade of ERK1/2 with
      either U0126 or PD98059, and by RhoA inactivation with C3 toxin or a dominant
      negative RhoA (N19RhoA), and was stimulated by the serine-threonine phosphatase
      inhibitor calyculin A. Our data thus identify a pathway of cPLA(2)alpha
      regulation that is initiated by thrombin and purinergic receptor activation, and
      that signals through Galpha(13), RhoA and ERK1/2, with the involvement of a
      calyculin-sensitive phosphatase.

PMID- 16806824
TI  - Low cell cholesterol levels increase NFkappaB activity through a p38 MAPK
      dependent mechanism.
AB  - Cholesterol, p38 MAPK and NFkappaB have been shown to participate in inflammation
      and cellular differentiation. Here, we examined the effect of cholesterol on
      NFkappaB-dependent transcription and the mechanisms underlying this effect in
      NIH3T3 cells. We show that chronic cholesterol depletion achieved with
      lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment
      resulted in a significant increase in NFkappaB-dependent transcription, NFkappaB
      DNA binding, IkappaBalpha degradation and p65/NFkappaB translocation to the
      nucleus, and the addition of exogenous cholesterol reversed these effects.
      Previously, we have shown that low cell cholesterol levels activate p38 MAPK.
      Here, we found that inhibition of p38 MAPK with the specific inhibitor SB203580
      blocked the increase in NFkappaB activity, IkappaBalpha degradation and
      p65/NFkappaB translocation to the nucleus induced by cholesterol depletion.
      Moreover, the inhibition of the p38 MAPK downstream effector MSK1 with the
      specific inhibitor H89, or the overexpression of a kinase defective MSK1
      abrogated the NFkappaB-dependent transcription induced by cholesterol depletion.
      On the other hand, the transactivation potential of p65/NFkappaB depends on
      phosphorylation of S276 by MSK1. We observed that cholesterol depletion increased
      the p65/NFkappaB transactivation capacity. This effect was reversed by cell
      cholesterol repletion or incubation with the SB203580 inhibitor. Moreover, the
      expression of a p65/NFkappaB S276A mutant was insensitive to cholesterol
      depletion. Together, our results demonstrate that cholesterol depletion induces
      NFkappaB transcriptional activity, not only by affecting the IkappaBalpha
      degradation and the translocation of p65/NFkappaB to the nucleus, but also
      regulating the p65/NFkappaB transactivating potential through a p38 MAPK/MSK1
      mediated pathway.

PMID- 16806825
TI  - Effects of interleukin-1beta on hippocampal glutamate and GABA releases
      associated with Ca2+-induced Ca2+ releasing systems.
AB  - Recent clinical and basic studies have demonstrated that hyperactivation of
      interleukin-1beta (IL-1beta) plays important roles in generation of febrile and
      epileptic seizures. To clarify this mechanism, the present study determined the
      effects of IL-1beta on Ca2+-associated releases of glutamate and GABA in mouse
      hippocampus. Both basal and K+-evoked GABA releases were regulated by Ca2+ influx
      and Ca2+-induced Ca2+ releasing system (CICR). The K+-evoked glutamate release
      was also regulated by Ca2+ influx and CICR, whereas basal glutamate release was
      not affected by them. IL-1beta increased basal releases of glutamate and GABA
      depending on the activation of Ca2+ influx and ryanodine receptor (RyR)-sensitive
      CICR, but reduced K+-evoked releases depending on Ca2+ influx, RyR-sensitive and
      inositol 1,4,5-trisphosphate receptor (IP3R)-sensitive CICRs. During neuronal
      hyperexcitability, the effect of IL-1beta on GABA release was more predominantly
      modulated by Ca2+ influx and RyR-sensitive CICR than that on glutamate. These
      results indicate that hyperactivation of IL-1beta leads to imbalance between
      glutamatergic and GABAergic transmission via toxic overload response of Ca2+
      influx and CICR.

PMID- 16806826
TI  - Clinical spectrum of mutations in SCN1A gene: severe myoclonic epilepsy in
      infancy and related epilepsies.
AB  - Severe myoclonic epilepsy in infancy (SMEI) manifests very frequent generalized
      tonic-clonic seizures (GTC), accompanied by myoclonic seizures, absences and
      partial seizures [Dravet, C., 1978. Les epilepsie grave de l'enfant. Vie Med. 8,
      543-548; Dravet, C., Roger, J., Bureau, M., Dalla Bernardina, B., 1982. Myoclonic
      epilepsies in childhood. In: Akimoto, H., Kazamatsuri, H., Seino, M., Ward, A.
      (Eds.), Advances in Epileptology. Raven Press, New York, pp. 135-140; Dravet, C.,
      Bureau, M., Oguni, H., Fukuyama, Y., Cokar, O., 2002. Severe myoclonic epilepsy
      of infancy (Dravet syndrome). In: Roger, J., Bureau, M., Dravet, C., Genton, P.,
      Tassinari, C.A., Wolf, P. (Eds.), Epileptic Syndromes in Infancy, Childhood and
      Adolescence, third ed. John Libbey, London, pp. 81-103]. However, there is a
      group of severe epilepsy that has many characteristics common to SMEI except for
      myoclonic seizures. We reported this group of epilepsy as intractable childhood
      epilepsy with GTC (ICEGTC) [Watanabe, M., Fujiwara, T., Yagi, K., Seino, M.,
      Higashi, T., 1989b. Intractable childhood epilepsy with generalized tonic-clonic
      seizures. J. Jpn. Epil. Soc. 7, 96-105 (in Japanese); Fujiwara, T., Watanabe, M.,
      Takahashi, Y., Higashi, T., Yagi, K., Seino, M., 1992. Long-term course of
      childhood epilepsy with intractable grand mal seizures. Jpn. J. Psychiatr.
      Neurol. 46, 297-302]. Recently, mutations of the neuronal voltage-gated sodium
      channel alphasubunit type 1 gene (SCN1A) have been found in SMEI [Claes, L., Del
      Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., De Jonghe, P., 2001,
      De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic
      epilepsy of infancy. Am. J. Hum. Genet. 68, 327-1332]. Mutations in SCN1A are
      found in both SMEI and ICEGTC at high rates of 70-81%. The loci of the mutations
      seen in ICEGTC are quite similar to those found in SMEI, suggesting a genotypic
      continuity between these entities. The clinical spectrum of epilepsies harboring
      SCN1A mutations may be consisted of various phenotypes with GEFS+ on the mildest
      end and SMEI on the severest end of the spectrum.

PMID- 16806827
TI  - Interaction of valproic acid and carbapenem antibiotics with multidrug resistance
      associated proteins in rat erythrocyte membranes.
AB  - We recently reported that the decrease in plasma valproic acid (VPA) level by
      carbapenem antibiotics (CPs) may partly be due to the increased erythrocyte
      distribution of VPA. In order to clarify the mechanisms underlying altered VPA
      distribution in erythrocytes, we examined the role of multidrug resistance
      associated proteins (Mrps). The uptake of 2,4-dinitrophenyl-S-glutathione (DNP
      SG), a substrate of Mrps, by inside-out vesicles (IOVs) prepared from rat
      erythrocytes was an ATP-dependent, active process. DNP-SG uptake was mediated by
      high- and low-affinity transport systems, and was inhibited by various Mrp
      inhibitors such as probenecid and indomethacin. Glutathione stimulated only the
      high-affinity transport system. VPA inhibited the low-affinity transport of DNP
      SG, while panipenem, a CP, inhibited both high- and low-affinity transport. ATP
      dependent, Mrp-mediated transport of methotrexate, another Mrp substrate, in IOVs
      was also observed, and VPA and various CPs inhibited the transport. The uptake of
      [(3)H]VPA was examined, and found to be ATP-dependent. ATP-dependent uptake of
      [(3)H]VPA was inhibited by Mrp inhibitors and panipenem, while the inhibition was
      not observed in the absence of ATP. These results indicate that VPA and CPs
      interact with Mrp-mediated transport in erythrocyte membranes, and VPA itself is
      transported by Mrps, which is inhibited by panipenem. Thus, the increased
      erythrocyte distribution of VPA by CPs observed under in vivo conditions may
      partly be explained by their interaction with Mrps in erythrocyte membranes.

PMID- 16806828
TI  - A new paradigm for West syndrome based on molecular and cell biology.
AB  - Symptomatic West syndrome has heterogeneous backgrounds. Recently, two novel
      genes, ARX and CDKL5, have been found to be responsible for cryptogenic West
      syndrome or infantile spasms. Both are located in the human chromosome Xp22
      region and are mainly expressed and play roles in fetal brain. Moreover, several
      genes responsible for brain malformations including lissencephaly, which is
      frequently associated with West syndrome or infantile spasms, have been found,
      and the mechanisms responsible for the neural network disorders in these brain
      malformations are rapidly being determined. Findings of animal and in vitro
      studies and mutation analyses in humans are delineating the molecular and
      cellular basis of West syndrome. Mutations of the ARX gene controlling the
      development of GABAergic interneurons exhibit pleiotropic effects including
      lissencephaly with a strong genotype-phenotype correlation. An expansion mutation
      of the first polyalanine tract of ARX is more strongly related to infantile
      spasms than is that of the second polyalanine tract. Although the phenotype of
      CDKL5 mutation is similar to Rett syndrome caused by MECP2 mutation, the former
      is characterized by early-onset seizures and association with West syndrome.
      Lissencephaly caused by LIS1 or DCX mutation frequently results in West syndrome,
      while lissencephaly due to ARX mutation is associated with the most severe form
      of epilepsy but never results in West syndrome nor infantile spasms. Both LIS1
      and DCX participate in the development of GABAergic interneurons as well as
      pyramidal neurons, while ARX participates only in that of interneurons.
      Individuals with lissencephaly due to ARX mutation lack non-pyramidal or
      GABAergic interneurons. ARX is crucial for the development of GABAergic
      interneuron, so abnormal interneurons in patients with ARX mutation are thought
      to be implicated in the pathological mechanism, even though brain MRI is normal.
      Abnormal interneurons appear to play an essential role in the pathogenesis of
      West syndrome or infantile spasms, which can be considered an interneuronopathy.

PMID- 16806829
TI  - Children with ESES: variability in the syndrome.
AB  - OBJECTIVE: We undertook a retrospective study of children who present with
      significant activation of paroxysmal discharges during sleep to examine the
      clinical spectrum of disorders that present with such an EEG abnormality.
      BACKGROUND: Electrical status epilepticus in sleep (ESES) is an electrographic
      pattern characterized by nearly continuous spike-wave discharges in slow wave
      sleep, usually with a frequency of 1.5-3 Hz and usually diffuse and bilateral in
      distribution. A variety of neurocognitive and behavioral problems have been
      associated with this EEG pattern. METHODS: We conducted a retrospective review of
      1497 EEG records of patients admitted to University of California, Los Angeles
      (UCLA) for overnight video-EEG monitoring during a 5 year interval. Demographic,
      clinical and electroencephalographic variables were evaluated. RESULTS: EEG
      records for 102 patients meeting criteria were identified. Clinical information
      was available for 90 of those patients. Eighteen of these patients could be
      diagnosed with Landau-Kleffner syndrome (LKS). Key findings include: (1)
      neuroimaging abnormalities were uncommon in our LKS patients; (2) among children
      who do not fit the specific diagnostic criteria for LKS, a spike-wave index (SWI)
      >50% was more likely to be associated with global developmental disturbances than
      SWI < or =50% (p<0.05); (3) Children with generalized discharges were more likely
      to experience severe or global developmental disturbance than those with focal
      abnormalities, without reaching statistical significance (p=0.07). CONCLUSIONS:
      Severity of ESES can vary over time between and within patients and clinical
      status does not always directly correlate with SWI. However, the prognosis of LKS
      is substantially better than CSWS and these two disorders could be classified in
      a dichotomous manner rather than be seen as two points along a continuum.

PMID- 16806830
TI  - Unilateral cortical spreading depression is an early marker of audiogenic
      kindling in awake rats.
AB  - Spreading depression (SD), a self-propagating wave of reversible cellular
      depolarization, is thought to play an important role in brain pathophysiology. SD
      and seizures are closely related events but little is known about involvement of
      SD in chronic epileptogenesis. Here we show that cortical SD is the first and
      highly reproducible manifestation of audiogenic kindling induced by repeated
      sound stimulation of WAG/Rij rats with genetic audiogenic and absence epilepsy.
      Repetition of sound-induced running seizures in freely moving rats led to an
      appearance and gradual intensification of post-running facial and forelimb clonic
      convulsions coupled with afterdischarge in the fronto-parietal cortex. Before the
      development of these traditional manifestations of audiogenic kindling, an
      unilateral cortical SD wave began to be triggered by audiogenic seizures. Once
      cortical SD appeared, it became a permanent component of subsequent seizures. SD
      was always recorded in the hemisphere ipsilateral to the running direction. Only
      at the late stages of audiogenic kindling SD developed bilaterally. To estimate
      the contribution of SD in postictal effects of audiogenic seizures, we compared
      cortical activity after seizures induced SD or not. It was found that only
      seizures with cortical SD were followed by postictal suppression of spontaneous
      spike-wave discharges displayed by WAG/Rij rats. The results show that (1)
      cortical SD is readily triggered by brief sensory-induced seizures in awake
      animals; (2) SD may be responsible for postictal changes in cortical activity;
      (3) unilateral initiation of SD suggests asymmetrical recruitment of the cortex
      into seizure network during audiogenic kindling.

PMID- 16806831
TI  - Examining the role of common genetic variation in the gamma2 subunit of the
      GABA(A) receptor in epilepsy using tagging SNPs.
AB  - INTRODUCTION: Mutations in the gamma2 subunit gene of the GABA(A) receptor,
      GABRG2, have been shown to cause generalised epilepsy syndromes in rare familial
      cases. Here we set out to examine whether common variation in GABRG2 predisposes
      to the development of common, complex forms of epilepsy in two large independent
      cohorts. METHODS: We have applied a tagging single nucleotide polymorphism (tSNP)
      technique allowing us to satisfactorily represent common variation in the gene.
      However, to ensure maximal representation of functional variation and in
      particular in cases of low minor allele frequency (MAF), we have identified and
      forced known functional variation as tagging SNPs. We examined the association
      between tagging SNPs and subtypes of epilepsy in two independent cohorts; the
      first consisted of 677 cases and 384 healthy controls, the second of 684 cases
      and 277 healthy controls. RESULTS: We failed to detect any variation that
      conferred an increased risk of disease development in both cohorts. DISCUSSION:
      Our results suggest that common variants of strong effect in GABRG2 do not appear
      to play a role in the development of common, complex forms of epilepsy. This
      report illustrates a number of important features of study design in genetic
      association studies, including the simultaneous use of map and sequence-based
      techniques and the necessity of replication before robust conclusions can be
      drawn from results.

PMID- 16806832
TI  - Landau-Kleffner syndrome is not an eponymic badge of ignorance.
AB  - In a 1992 editorial article, Landau expressed the hope of collective agreement in
      the medical community about Landau-Kleffner syndrome (LKS) in terms of diagnosis
      criteria, etiology, pathophysiology and rational therapy. Since then,
      neurophysiological and neuroimaging studies have led to the view that LKS is an
      acquired aphasia, secondary to an epileptic disturbance affecting a cortical area
      involved in verbal processing. This fits with the hypothesis of a "functional
      ablation" caused by epileptic activity. Under these criteria, epileptic aphasia
      becomes a subgroup of the continuous spike-waves syndrome in which epileptic
      discharges originate from the temporal cortex. Genetic predisposition for KLS
      could be related to hyperexcitability and synchronization of interneurons within
      the perisylvian cortices, which generate the spike-waves. Activation of these
      waves during NREM sleep, following thalamo-cortical uncoupling, might then alter
      the blood brain barrier and provoke an autoimmune reaction. Interneuron
      hyperactivity might in turn have an antiepileptic protective effect, associated
      with the inhibition of a specific function, and spike-waves activity over the
      long term might eventuate in focal atrophy. This morphological defect might
      explain the poor verbal outcome in some cases of LKS. From this study we
      recommend a multicenter control study of good design and methodology be carried
      out to compare the efficacies of early versus delayed (3 months) corticosteroid
      treatment in patients with typical LKS that is being treated by clobazam (or
      diazepam) monotherapy.

PMID- 16806833
TI  - A neuropsychological study of patients with temporal lobe epilepsy and chronic
      interictal psychosis.
AB  - PURPOSE: To characterize the pattern of cognitive deficits in patients with
      temporal lobe epilepsy (TLE) and interictal (schizophrenia-like) psychosis and to
      examine the relationship between neuropsychological deficits and Magnetization
      transfer imaging. METHODS: Twenty patients with TLE and interictal psychosis were
      compared to 20 non-psychotic TLE patients. Patients were matched with respect to
      premorbid IQ, age and conventional MRI findings. A battery of neuropsychological
      tests was administered. The neuropsychological tests which showed significant
      group differences were used for correlational analysis with magnetization
      transfer ratio (MTR) which provides a quantitative measure of macromolecular
      structural integrity. RESULTS: Patients with interictal psychosis were
      significantly more impaired on executive and semantic memory tasks than the non
      psychotic TLE group. Vocabulary test scores correlated significantly with MTR
      reduction in the left fusiform gyrus in the psychotic but not the non-psychotic
      group. DISCUSSION: In this study, patients with TLE and interictal psychosis were
      more cognitively impaired than non-psychotic TLE patients. Our findings suggest
      that the cognitive deterioration in these patients may occur as the illness
      progresses and the causes for this are probably multifactorial. Our study also
      provides further evidence that MTR may be useful in investigating structural
      correlates of cognitive impairment.

PMID- 16806834
TI  - Na channel gene mutations in epilepsy--the functional consequences.
AB  - Mutations of voltage-gated sodium channel genes SCN1A, SCN2A, and SCN1B have been
      identified in several types of epilepsies including generalized epilepsy with
      febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI). In
      both SCN1A and SCN2A, missense mutations tend to result in benign idiopathic
      epilepsy, whereas truncation mutations lead to severe and intractable epilepsy.
      However, the results obtained by the biophysical analyses using cultured cell
      systems still remain elusive. Now studies in animal models harboring sodium
      channel gene mutations should be eagerly pursued.

PMID- 16806835
TI  - Sex differences in digit ratio (2D:4D) are disrupted in adolescents with
      schizotypal personality disorder: altered prenatal gonadal hormone levels as a
      risk factor.
AB  - The 2nd to 4th finger digit ratio (2D:4D) is a sexually dimorphic feature
      determined during gestation indexing prenatal androgen/estrogen levels. More
      'feminized' 2D:4D phenotype has been demonstrated in schizophrenia versus same
      sex controls. This study examined 2D:4D in adolescents with schizotypal
      personality disorder (SPD). Among normal controls, right 2D:4D was significantly
      greater (more feminized) in females than males. We replicated laterality effects;
      significant sex differences only on right. There were no significant sex
      differences among SPDs. Diagnostic group differences were restricted to
      White/Caucasian males with greater right 2D:4D in SPDs. Findings suggest
      disruptions in prenatal gonadal hormones in vulnerability for schizophrenia.

PMID- 16806836
TI  - Evidence that brain tissue volumes are associated with HVA reactivity to
      metabolic stress in schizophrenia.
AB  - BACKGROUND: Although liability to psychosis is thought to have its origins in
      cerebral alterations, expressed as cerebral grey and white matter loss, less is
      known about the degree to which such vulnerabilities impact on functional
      parameters, in particular altered stress reactivity. Breier et al. [Breier, A.,
      Davis, O.R., Buchanan, R.W., Moricle, L.A., Munson, R.C., 1993b. Effects of
      metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship
      to prefrontal cortex volume. Arch. Gen. Psychiatry 50(7), 541-550] reported that
      lower prefrontal cortex volume was associated with altered metabolic stress
      response, but this finding has never been replicated. METHODS: Thirty-one
      patients with psychosis underwent structural magnetic resonance imaging scanning
      and a metabolic stress paradigm (glucoprivic 2-deoxyglucose (2DG) condition
      versus placebo condition) that yielded information on plasma homovanillic acid
      (HVA) reactivity. Total cerebral tissue volumes were derived from automated
      segmentation procedures. Associations between metabolic stress and tissue volumes
      (as well as their interactions) on the one hand, and plasma HVA level on the
      other, were investigated using multilevel random regression techniques. RESULTS:
      Analysis revealed a significant increase in plasma HVA over time in the 2DG
      condition. The increase in HVA in the stress condition was stronger in patients
      with lower grey and white matter volumes. There was no significant interaction
      between metabolic stress and CSF volume. CONCLUSION: Lower grey and white matter
      volumes in schizophrenia are associated with a dysregulated
      dopaminergic/noradrenergic mediated stress response. These findings may support
      the hypothesis that alterations in cortico-subcortical connections affect
      psychosis susceptibility through an altered stress response.

PMID- 16806837
TI  - Lifetime positive symptoms in patients with schizophrenia and cannabis abuse are
      partially explained by co-morbid addiction.
AB  - Recent prospective findings have shown that cannabis use by young people could be
      a risk factor for psychotic symptoms in adulthood, but the long-term impact of
      cannabis abuse on the clinical features of declared schizophrenia remains to be
      explored. We assessed the independent influence of cannabis abuse on the clinical
      symptoms of schizophrenia, after controlling for frequently co-occurring
      addictive disorders. Patients with schizophrenia, and with (N=66), or without
      (N=139) cannabis abuse, were compared for lifetime positive and negative
      symptoms, taking into account presence of any other addictive disorders. The
      incidence of the abuse of drugs other than cannabis was nearly five times greater
      amongst patients with both schizophrenia and cannabis abuse. When the analyses
      were limited to subjects with no other abuse, less avolution and fewer apathy
      symptoms were still detected in patients with schizophrenia and cannabis abuse
      than in those with no abuse (p=0.0001). In contrast, between-group differences
      for positive symptoms were abolished when multiple substance abuses were taken
      into account. The strong association between cannabis abuse and fewer negative
      symptoms in schizophrenia was thus replicated in this sample, but once co-morbid
      addictive disorders had been controlled no influence of cannabis abuse on
      hallucinations was detected. Distinguishing the effects of co-occurring addictive
      disorder(s) in patients with schizophrenia and cannabis dependence may thus be
      important when attempting to analyse the impact of cannabis abuse.

PMID- 16806838
TI  - Do you hear what I hear? Neural correlates of thought disorder during listening
      to speech in schizophrenia.
AB  - Thought disorder is a fundamental symptom of schizophrenia, observable as
      irregularities in speech. It has been associated with functional and structural
      abnormalities in brain regions involved in language processing, including left
      temporal regions, during language production tasks. We were interested in the
      neural correlates of thought disorder during receptive language processing, as
      this function is relatively preserved despite relying on the same brain regions
      as expressive language. Twelve patients with schizophrenia and 11 controls
      listened to 30-s speech samples while undergoing fMRI scanning. Thought disorder
      and global symptom ratings were obtained for each patient. Thought disorder but
      not global symptomatology correlated positively with the BOLD response in the
      left posterior superior temporal lobe while listening to comprehensible speech
      (cluster-level corrected p=.023). The pattern of brain activity associated with
      thought disorder during listening to comprehensible speech differs from that seen
      during language generation tasks, where a reduction of the leftward laterality of
      language has often been observed. As receptive language is spared in thought
      disorder, we propose that the increase in activation reflects compensatory
      processing allowing for normal performance.

PMID- 16806839
TI  - A comparison of outcomes among patients with schizophrenia in two mental health
      systems: a health state approach.
AB  - This paper introduces a health state modeling approach using clustering and
      Markov analysis to compare short- and long-term outcomes among health care
      populations. We provide a comparison to more conventional mixed effects
      regression methods and show that discrete state modeling offers a richer portrait
      of patient outcomes than the standard univariate techniques. We demonstrate our
      approach using primary data from a three year observational study of patients
      treated for schizophrenia at a VA Medical Center (VA) and in a Community Mental
      Health Center (CMHC) in the same urban community. Randomly selected samples of
      outpatients treated for schizophrenia or schizoaffective disorder were
      interviewed every six months using standardized psychiatric assessments such as
      the Positive and Negative Syndrome Scale (PANSS). Items from the PANSS were used
      to define 7 discrete health states representing different levels of severity and
      diverse mixtures of psychiatric symptoms. Conventional analysis showed that VA
      patients exhibited increasingly severe symptoms, while CMHC patients remained
      more stable over the study period. Health state analysis reinforced these results
      but also identified which subpopulations of VA patients were deteriorating. In
      particular they showed that there was little change over time among VA patients
      in the best and worst health states. Instead the deterioration was caused by VA
      patients with: a) mild symptoms and hallucinations and b) serious positive and
      negative symptoms, being more likely to enter a state with severe positive and
      negative symptoms accompanied by moderate general distress.

PMID- 16806840
TI  - Proteolytic cleavage of Livin (ML-IAP) in apoptotic melanoma cells potentially
      mediated by a non-canonical caspase.
AB  - BACKGROUND: Several inhibitor of apoptosis proteins (IAPs) are cleaved during
      apoptosis. Studies of the melanoma-associated IAP (ML-IAP) Livin, using
      recombinant molecules, have implicated both caspases 3/7 and the serine protease
      Omi/HtrA2 in its proteolytic cleavage. OBJECTIVE: To characterize the apoptotic
      cleavage of Livin in melanocytic cells, and evaluate the role of known proteases.
      METHODS: We assessed the capacity of a variety of stimuli to induce Livin
      cleavage in human melanoma cell lines and normal human melanocytes. The role of
      caspases and Omi was examined using caspase inhibitors and RNAi, respectively. A
      potential caspase substrate was further examined by site-directed mutagenesis.
      Deletion mapping was used to identify the cleavage site. RESULTS: Livin cleavage
      was observed in multiple human melanoma cell lines in response to a variety of
      apoptotic stimuli (UVB, 4-TBP, cisplatin, TNF, Bax), and not affected by the
      addition of various protease inhibitors or RNAi-mediated silencing of Omi/HtrA2.
      Livin cleavage induced by 4-TBP, but not UVB or cisplatin, was blocked by the pan
      caspase inhibitor zVAD-fmk. Mutation of Asp52 to Glu in Livin did not affect
      cleavage, while either mutation of Asp52 to Ala, deletion of Asp52, or deletion
      of the adjacent region (residues 53-61) abrogated cleavage. CONCLUSION: Livin
      cleavage, induced by multiple apoptotic stimuli in melanoma cells, likely occurs
      in an Omi-independent fashion at residue 52 within its potential caspase
      substrate (DHVD52). However, relative insensitivity of the apoptotic cleavage to
      zVAD-fmk, or Asp52 to Glu mutation, suggests the involvement of a non-canonical
      caspase.

PMID- 16806841
TI  - Pimecrolimus and tacrolimus differ in their inhibition of lymphocyte activation
      during the sensitization phase of contact hypersensitivity.
AB  - BACKGROUND: As reported previously, oral administration of the calcineurin
      inhibitors (CNI) pimecrolimus and tacrolimus resulted in equipotent inhibition of
      the elicitation phase of contact hypersensitivity (CHS) in mice. The
      sensitization phase was inhibited by tacrolimus but was unaffected by
      pimecrolimus, even at higher doses. OBJECTIVE: The kinetics of lymph node
      hyperplasia and up-regulation of T and B cell activation antigens were analyzed
      to obtain a better understanding of the divergent CNI profile in CHS. METHODS:
      Lymph node (LN) cells of CNI-untreated and treated mice were examined with flow
      cytometry at various time points after sensitization with oxazolone. LN
      hyperplasia and drug levels were also determined. RESULTS: Sensitization induced
      a higher portion of LN cells expressing the activation antigens CD25, CD69 and
      CD134 and an increase in activated B cells (B220(+)/CD40(+)) compared to naive
      mice. Up-regulation of these markers was completely or profoundly blocked with
      tacrolimus, whereas pimecrolimus at the three-fold higher dose caused
      significantly less inhibition. Tacrolimus also completely blocked the
      sensitization-associated increase of CD11c(+) antigen presenting cells (APC) in
      LN, whereas pimecrolimus showed significantly less inhibition. In contrast to
      tacrolimus, LN weight and cellularity were not affected by pimecrolimus at any
      time point after sensitization. Concentration of tacrolimus in blood and in the
      draining LN substantially exceeded that of pimecrolimus by factors 6.7-14 and 5.6
      5.8, respectively, at the same dose levels. CONCLUSION: In contrast to
      tacrolimus, systemic treatment of mice with pimecrolimus only weakly interferes
      with lymphocyte activation and does not affect hyperplasia of the draining lymph
      nodes during sensitization.

PMID- 16806842
TI  - The real-time, three-dimensional analyses of benign and malignant skin tumors by
      confocal laser scanning microscopy.
AB  - BACKGROUND: In obtain images of skin tumors non-invasively with real-time,
      confocal laser scanning microscope (CLSM) is introduced. OBJECTIVE: Reconstructed
      images of given horizontal sections were converted into three-dimensions using
      the data set of a large number of tomograms in the horizontal directions.
      METHODS: To develop the multiplaner reconstruction images of skin tumors in
      vertical directions and three-dimensionally reconstructed images of tumors will
      be obtained from the continuously collected horizontal image data sets. RESULTS:
      Three-dimensional analyses of the skin tumors from reconstructed images of the
      CLSM scanning have provided the information as to their physiological
      characteristics as well as the extent of deep invasion in real-time with non
      invasive manner. High performance three-dimensional conversion software was
      effective in displaying three-dimensional construction of skin tumors.
      CONCLUSION: The CLSM scanning images followed by three-dimensional reconstruction
      using them can provide the real-time and non-invasive diagnoses of skin tumors
      and analyze the radial growth phase of tumors and the three-dimensional growth
      characteristics.

PMID- 16806843
TI  - Gene Therapy for ALS: progress and prospects.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating disease for which there are
      no effective drug treatments to date. Recent advances in Gene Therapy open up the
      possibility of developing an effective treatment aiming at halting or delaying
      the degeneration of motor neurons. Viral vectors such as lentiviral vectors and
      adeno-associated virus can transfer genes into many different types of primary
      neurons from a broad range of species including man and the resulting gene
      expression is long-term. Numerous animal studies have now been undertaken with
      these vectors and correction of disease models has been obtained. These vectors
      have been refined to a very high level and can be produced safely for the clinic.
      However, we believe that there are some major issues that need to be addressed in
      order to see a Gene Therapy approach with viral vectors proceed to the clinic for
      ALS patients. This review will describe the general features of lentiviral
      vectors. It will then describe some key examples of gene transfer and genetic
      correction in animal models of motor neuron disease. The prospects for the
      clinical evaluation of lentiviral vectors for the treatment of human motor neuron
      disease will be outlined.

PMID- 16806844
TI  - The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis.
AB  - Unfortunately and despite all efforts, amyotrophic lateral sclerosis (ALS)
      remains an incurable neurodegenerative disorder characterized by the progressive
      and selective death of motor neurons. The cause of this process is mostly
      unknown, but evidence is available that excitotoxicity plays an important role.
      In this review, we will give an overview of the arguments in favor of the
      involvement of excitotoxicity in ALS. The most important one is that the only
      drug proven to slow the disease process in humans, riluzole, has anti-excitotoxic
      properties. Moreover, consumption of excitotoxins can give rise to selective
      motor neuron death, indicating that motor neurons are extremely sensitive to
      excessive stimulation of glutamate receptors. We will summarize the intrinsic
      properties of motor neurons that could render these cells particularly sensitive
      to excitotoxicity. Most of these characteristics relate to the way motor neurons
      handle Ca(2+), as they combine two exceptional characteristics: a low Ca(2+)
      buffering capacity and a high number of Ca(2+)-permeable AMPA receptors. These
      properties most likely are essential to perform their normal function, but under
      pathological conditions they could become responsible for the selective death of
      motor neurons. In order to achieve this worst-case scenario, additional
      factors/mechanisms could be required. In 1 to 2% of the ALS patients, mutations
      in the SOD1 gene could shift the balance from normal motor neuron excitation to
      excitotoxicity by decreasing glutamate uptake in the surrounding astrocytes
      and/or by interfering with mitochondrial function. We will discuss point by point
      these different pathogenic mechanisms that could give rise to classical and/or
      slow excitotoxicity leading to selective motor neuron death.

PMID- 16806845
TI  - Implication of nanos2-3'UTR in the expression and function of nanos2.
AB  - Translational control of gene expression is an important component of the
      regulation of cellular differentiation and development. To elucidate the function
      of the 3'untranslated region (UTR) of the nanos2 gene in mice, we compared the
      phenotypes of lacZ knock-in mice with or without a native nanos2 3'UTR and found
      that this region of the nanos2 gene has a potential role during translational
      regulation in germ cells. The nanos2-3'UTR functions to repress the translation
      of mRNA in oocytes, but enhances the production of protein in the male gonads. To
      further understand the significance of the nanos2 3'UTR in vivo, we generated the
      mouse line nanos2pA/pA, which lacks this region endogenously. In nanos2(-/pA)
      mice, the number of germ cell-depleted seminiferous tubules was increased when
      compared with that of nanos2pA/pA mice, indicating a dose-dependent defect in
      spermatogenesis. These results suggest that the level of nanos2 protein is
      critical for normal spermatogenesis, and that this pathway may be regulated
      through the nanos2-3'UTR. We found that the defects in nanos2pA/pA and nanos2(
      /pA) mice were caused by apoptosis of gonocytes in the embryonic gonads and
      gonocyte/spermatogonia in neonatal testes. In addition, it was noted that the
      nanos2 expression was restricted to a particular subset of spermatogonia after
      birth, which indicates that nanos2 plays a role in the maintenance and
      differentiation of gonocytes/spermatogonia in neonatal testes.

PMID- 16806846
TI  - Maintenance of segment and appendage primordia by the Tribolium gene knodel.
AB  - For homeotic and segment-polarity genes in Drosophila, a switch in gene
      regulation has been described that distinguishes patterning and maintenance
      phases. Maintenance of segment and organ primordia involves secondary patterning
      and differentiation steps, as well as survival factors regulating proliferation
      and organ size. In a screen for embryonic lethal mutations in the flour beetle
      Tribolium castaneum, we have recovered two alleles of the knodel gene, which
      result in short, bag-like embryos. These embryos have severely reduced appendages
      and differentiate a cuticle that lacks most overt signs of segmentation. In
      addition, they lack bristles and display defects in the nervous system. Early
      patterning in knodel mutant embryos is normal up to the extended germ band stage,
      as indicated by the formation of regular even-skipped (Tc'eve) and wingless
      (Tc'wg) stripes. Afterwards, however, these patterns degenerate. Similarly,
      proximo-distal growth and patterning of limbs are nearly normal initially, but
      limb primordia shrink, and proximo-distal patterns degenerate, during subsequent
      stages. knodel could be a segment polarity gene required for segment border
      maintenance in both trunk and appendages. Alternatively, it may have a more
      general role in tissue or organ maintenance.

PMID- 16806847
TI  - Evidence for activation of Amh gene expression by steroidogenic factor 1.
AB  - The anti-Mullerian hormone gene (Amh) is responsible for regression in males of
      the Mullerian ducts. The molecular mechanism of regulation of chicken Amh
      expression is poorly understood. To investigate the regulation of chicken Amh
      expression, we have cloned Amh cDNAs from quail and duck as well as the promoter
      regions of the gene from chicken, quail, and duck. The expression patterns of Amh
      during embryonic development in these three species were found to be similar,
      suggesting that the regulatory mechanisms of Amh expression are conserved. The
      sequence of the proximal promoter of Amh contains a putative binding site for
      steroidogenic factor 1 (SF1), the protein product of which can up-regulate Amh in
      mammals. We showed here that SF1 is able to activate the chicken Amh promoter and
      binds to its putative SF1 binding site. These results suggest that SF1 plays a
      role in regulation of Amh expression in avian species.

PMID- 16806848
TI  - Gata3 is required for early morphogenesis and Fgf10 expression during otic
      development.
AB  - Inner ear develops from an induced surface ectoderm placode that invaginates and
      closes to form the otic vesicle, which then undergoes a complex morphogenetic
      process to form the membranous labyrinth. Inner ear morphogenesis is severely
      affected in Gata3 deficient mouse embryos, but the onset and basis of the
      phenotype has not been known. We show here that Gata3 deficiency leads to severe
      and unique abnormalities during otic placode invagination. The invagination
      problems are accompanied often by the formation of a morphological boundary
      between the dorsal and ventral otic cup and by the precocious appearance of
      dorsal endolymphatic characteristics. In addition, the endolymphatic domain often
      detaches from the rest of the otic epithelium during epithelial closure. The
      expression of several cell adhesion mediating genes is altered in Gata3 deficient
      ears suggesting that Gata3 controls adhesion and morphogenetic movements in early
      otic epithelium. Inactivation of Gata3 leads also to a loss of Fgf10 expression
      in otic epithelium and auditory ganglion demonstrating that Gata3 is an important
      regulator of Fgf-signalling during otic development.

PMID- 16806849
TI  - Neural correlates of habituation to taste stimuli in healthy women.
AB  - Recent studies show that specific regions of the cortex contribute to modulation
      of appetitive behaviors. The purpose of this study was to determine whether
      neural response in these regions changes over time when a taste stimulus is
      administered repeatedly. Such a paradigm may be useful for determining whether
      altered habituation contributes to disturbed eating behavior. This study used a
      programmable syringe pump to compare administration of a 10% sucrose solution to
      distilled water in 11 healthy female subjects using functional magnetic resonance
      imaging. The stimuli were presented in either a sequential or pseudorandom order.
      An a priori 'Region of Interest' (ROI) based analysis method was used, with ROIs
      defined in the prefrontal cortex, insula, amygdala, and hippocampus. To test
      habituation, activation during the first half of each block was compared with
      activation during the second half. For the pseudorandom blocks, subjects showed
      habituation in almost all ROIs to water, but in none to sucrose. By contrast, for
      sequential blocks, both stimuli produced habituation in taste-related brain
      regions. These data suggest that habituation patterns in healthy subjects may
      depend on frequency and regularity of stimulus administration.

PMID- 16806850
TI  - Review of 1H magnetic resonance spectroscopy findings in major depressive
      disorder: a meta-analysis.
AB  - In a review of the current literature, we identified (1)H MRS studies of major
      depressive disorder (MDD) that examined the metabolites N-acetylaspartate (NAA),
      choline (Cho), myo-inositol (mI), glutamate/glutamine/gamma-aminobutyric acid
      GABA (Glx), and creatine (Cr). Separate meta-analyses comparing adult and
      pediatric MDD patients with healthy controls were performed. For adults, 14
      studies with 227 patients/246 controls for NAA, 15 studies with 240 patients/261
      controls for Cho, seven studies with 96 patients/104 controls for mI, six studies
      with 86 patients/109 controls for Glx, and nine studies with 146 patients/173
      controls for Cr were identified. There were six studies containing a total of 79
      pediatric depressed patients. We performed 15 separate meta-analyses to combine
      results from studies with similar characteristics. Adult MDD patients had higher
      Cho/Cr values than controls in the basal ganglia. In contrast, three studies on
      Glx levels indicated significantly lower Glx levels in the frontal lobe of MDD
      patients. The review indicated increased Cho/Cr in the basal ganglia in MDD and
      no alteration of NAA, suggesting an increased membrane turnover in MDD without a
      neurodegenerative outcome. Lower Glx levels in depressed patients in contrast to
      a likely hyperglutamatergic state in bipolar disorder may implicate a different
      pathophysiological ground in MDD.

PMID- 16806851
TI  - Dependence of chymosin and pepsin partition coefficient with phase volume and
      polymer pausidispersity in polyethyleneglycol-phosphate aqueous two-phase system.
AB  - The influence of the phase volume ratio and polymer pausidispersity on chymosin
      and pepsin partition in polyethylenglycol-phosphate aqueous two-phase systems was
      studied. Both proteins showed a high affinity for the polyethylenglycol rich
      phase with a partition coefficient from 20 to 100 for chymosin and from 20 to 180
      for pepsin, when the polyethyleneglycol molecular mass in the system varied
      between 1450 and 8000. The partition coefficient of chymosin was not affected by
      the volume phase ratio, while the pepsin coefficient showed a significant
      decrease in its partition coefficient with the increase in the top/bottom phase
      volume ratio.

PMID- 16806852
TI  - Influence of urea additives on micellar morphology/protein conformation.
AB  - The present study highlights the fact that the effect of additives (urea,
      monomethylurea, thiourea) on the supramolecular assemblies and proteins is
      strikingly similar. To investigate the effect, a viscometeric study on sphere-to
      rod transition (s-->r) was undertaken in a system (3.5%
      tetradecyltrimethylammonium bromide+0.05 M NaBr + 1-pentanol [P.M. Lindemuth,
      G.L. Bertand, J. Phys. Chem. 97 (1993) 7769]) in the presence and absence of the
      said additives. [1-pentanol] needed for s-->r (i.e. [1-pentanol]s-->r) was
      determined from the relative viscosity versus [1-pentanol] profiles. It was
      observed that the additives preponed as well as postponed s-->r depending upon
      their nature and concentrations. These effects are explained in terms of
      increased polarity of the medium and the adsorption ability of
      urea/monomethylurea on the charged surfactant monomers of the micelle. In case of
      thiourea, postponement of s-->r was observed throughout which is attributed to
      its structure. To derive an analogy between micelles and proteins the additive
      induced conformational changes of the protein, bovine serum albumin (BSA) was
      taken to monitor secondary structural changes and tryptophanyl fluorescence. A
      marked increase in secondary structure (far-UVCD) and increased tryptophanyl
      fluorescence with a marked blue shift in lambdamax was observed in presence of
      low concentrations of urea or alkylurea. This indicates that a more compact
      environment is created in presence of these additives, if added judiciously.
      Addition of thiourea to BSA caused a marked quenching without any significant
      change in lambdamax. The large decrease in tryptophanyl emission in presence of
      low thiourea concentrations seems to be specific and related to thiourea
      structure as no corresponding changes were observed in urea/alkylurea. All these
      effects pertaining to protein behavior fall in line with that of morphological
      observations on the present as well as surfactant systems studied earlier [S.
      Kumar, N. Parveen, Kabir-ud-Din, J. Phys. Chem. B 108 (2004) 9588].

PMID- 16806853
TI  - Surfactive water-soluble copolymers for the preparation of controlled surface
      nanoparticles by double emulsion/solvent evaporation.
AB  - We have already shown that polylactide (PLA) nanoparticles covered with a
      hydrophilic polymeric layer can be prepared by simple emulsion/solvent
      evaporation by using amphiphilic copolymers as surfactants during the procedure.
      The external layer is then constituted by the hydrophilic part of the
      macromolecular surfactant. This kind of nanospheres is useful for the
      encapsulation of lipohilic molecules. The use of amphiphilic copolymers as
      surfactants in the preparation of PLA nanospheres with controlled surface
      properties, was then applied to the double emulsion/solvent evaporation
      procedure. The aim was to allow the encapsulation of water-soluble bioactive
      molecules in PLA particles with controlled surface properties. In this paper, we
      describe the results obtained with three different water-soluble
      monomethoxypolyethylene oxide (MPEO)-b-PLA diblock copolymers used as surfactants
      in the preparation of nanoparticles by double emulsion/solvent evaporation. After
      organic solvent evaporation, the obtained nanospheres were proved to be really
      covered by a MPEO layer whose characteristics were determined. It was firstly
      shown that the MPEO-covered particles did not flocculate at 25 degrees C, even in
      4 M NaCl while suspensions of bare nanospheres were destabilized for a NaCl
      concentration as low as 0.04 M. On the other hand, the suspensions of MPEO
      covered nanoparticles in 0.3 M Na2SO4 were found to be very sensitive to
      temperature as they flocculated at a temperature lying between 45 and 55 degrees
      C depending on the MPEO-b-PLA composition. This property was attributed to the
      fact that MPEO is a polymer with a low critical solution temperature. The
      concentration of MPEO at the nanoparticle surface was then calculated for the
      three kinds of particles, from the initial flocculation temperature, and was
      found to be comparable to the value determined directly.

PMID- 16806854
TI  - Effect of surface proteins on Staphylococcus epidermidis adhesion and
      colonization on silicone.
AB  - Shunt infections are one of the most serious complications in shunt implant
      surgery. Previous studies have suggested that cerebrospinal fluid (CSF) proteins
      could affect bacterial adhesion and subsequent shunt infection. A systematic
      study using immobilized protein on the surface of silane-modified silicone was
      conducted to determine how these modifications influenced Staphylococcus
      epidermidis adhesion and colonization. A comparison was also made with silicone
      having physically adsorbed protein. A colony-counting adhesion assay and scanning
      electron microscopy (SEM) were used to provide quantitative analysis of bacterial
      adhesion and semi-quantitative analysis of bacterial colonization, respectively.
      In order to determine the appropriate silanization process for effective protein
      immobilization, the effect of bovine serum albumin (BSA) immobilized on n-3
      (trimethoxysilyl)propyl-ethylenediamine (AEAPS)/silicone,
      aminopropyltriethoxysilane (APTMS)/silicone, 3
      (glycidyloxypropyl)trimethoxysilane (GPTMS)/silicone, and
      octadecyltrichlorosilane (OTS)/silicone on bacterial adhesion was investigated.
      Upon identifying that OTS is the most effective silane, different types of
      proteins, including: BSA, human serum albumin (HSA), gamma-globulin, and
      fibrinogen were immobilized on OTS/silicone by a photo-immobilization method.
      Immobilized protein on modified silicone surfaces was found to be stable in
      saline for 30 days, while physically adsorbed protein showed instability within
      hours as determined by contact angle measurements and X-ray photoelectron
      spectroscopy (XPS). For HSA/OTS/silicone, BSA/OTS/silicone, gamma
      globulin/OTS/silicone, fibrinogen/OTS/silicon, and physically absorbed BSA on
      silicone, the contact angles were 78.5 degrees, 80.7 degrees, 78.9 degrees, 81.3
      degrees, and 96.5 degrees; and the amount of nitrogen content was found to be
      4.6%, 5.0%, 5.6%, 7.2%, and 3.2%, respectively. All protein immobilized on
      OTS/silicone surfaces significantly reduced bacterial adhesion by around 75%
      compared to untreated silicone, while physically adsorbed BSA on silicone reduced
      by only 29.4%, as determined by colony-counting adhesion assay. However, there
      was no significant difference on bacterial adhesion among the different types of
      proteins immobilized on OTS/silicone. Minimizing bacterial adhesion and
      colonization can be attributed to the increased concentration of -NH2 group, and
      stability and more hydrophilic nature of the protein/OTS/silicone surfaces.

PMID- 16806855
TI  - An integrated approach to model hepatic drug clearance.
AB  - It has been well accepted that hepatic drug extraction depends on the blood flow,
      vascular binding, transmembrane barriers, transporters, enzymes and cosubstrate
      and their zonal heterogeneity. Models of hepatic drug clearances have been
      appraised with respect to their utility in predicting drug removal by the liver.
      Among these models, the "well-stirred" model is the simplest since it assumes
      venous equilibration, with drug emerging from the outflow being in equilibrium
      with drug within the liver, and the concentration is the same throughout. The
      "parallel tube" and dispersion models, and distributed model of Goresky and co
      workers have been used to account for the observed sinusoidal concentration
      gradient from the inlet and outlet. Departure from these models exists to include
      heterogeneity in flow, enzymes, and transporters. This article utilized the
      physiologically based pharmacokinetic (PBPK) liver model and its extension that
      include heterogeneity in enzymes and transporters to illustrate how in vitro
      uptake and metabolic data from zonal hepatocytes on transport and enzymes may be
      used to predict the kinetics of removal in the intact liver; binding data were
      also necessary. In doing so, an integrative platform was provided to examine
      determinants of hepatic drug clearance. We used enalapril and digoxin as
      examples, and described a simple liver PBPK model that included transmembrane
      transport and metabolism occurring behind the membrane, and a zonal model in
      which the PBPK model was expanded three sets of sub-compartments that are
      arranged sequentially to represent zones 1, 2, and 3 along the flow path. The
      latter model readily accommodated the heterogeneous distribution of hepatic
      enzymes and transporters. Transport and metabolic data, piecewise information
      that served as initial estimates, allowed for the unknown efflux and other
      intrinsic clearances to be estimated. The simple or zonal PBPK model provides
      predictive views on the hepatic removal of drugs and metabolites.

PMID- 16806856
TI  - Biliary secretion of rosuvastatin and bile acids in humans during the absorption
      phase.
AB  - AIM: The aim of this study was to investigate the biliary secretion of
      rosuvastatin in healthy volunteers using an intestinal perfusion method after
      administration of 10mg rosuvastatin dispersion in the intestine. METHODS: The Loc
      I-Gut tube was positioned in the distal duodenum/proximal jejunum and a semi-open
      segment was created by inflating the proximal balloon in ten volunteers. A
      dispersion of 10mg rosuvastatin was administered below the inflated balloon and
      bile was collected proximally of the inflated balloon. Bile and plasma samples
      were withdrawn every 20 min during a 4h period (absorption phase) and additional
      plasma samples were collected 24 and 48 h post-dose. RESULTS: The study showed
      that there is a substantial and immediate transport of rosuvastatin into the
      human bile, with the maximum concentration appearing 42 min after dosing,
      39,000+/-31,000 ng/ml. Approximately 11% of the administered intestinal dose was
      recovered in the bile after 240 min. At all time points the biliary concentration
      exceeded the plasma concentration, and the average bile to plasma ratio was
      5200+/-9200 (range 89-33,900, median 2000). We were unable to identify any bile
      specific metabolites of rosuvastatin in the present study. CONCLUSION:
      Rosuvastatin is excreted via the biliary route in humans, and the transport and
      accumulation of rosuvastatin in bile compared to that in plasma is rapid and
      extensive. This intestinal perfusion technique offers a successful way to
      estimate the biliary secretion for drugs, metabolites and endogenous substances
      during the absorption phase in healthy volunteers.

PMID- 16806857
TI  - Cyclodextrins in the production of large porous particles: development of dry
      powders for the sustained release of insulin to the lungs.
AB  - The aim of this work was to develop dry powders intended for insulin pulmonary
      delivery. To this purpose, large porous particles (LPP) made of poly(lactide-co
      glycolide) (PLGA) were produced by the double emulsion-solvent evaporation
      technique. Hydroxypropyl-beta-cyclodextrin (HPbetaCD), also known as absorption
      enhancer for pulmonary protein delivery, was tested as aid excipient to optimize
      the aerodynamic behaviour of the microparticles. Several microsphere
      formulations, differing in HPbetaCD and insulin loadings, were produced and their
      properties compared. A contemporary release of insulin and HPbetaCD from the
      system can be achieved by selecting appropriate formulation conditions. HPbetaCD
      containing LPP with flow properties and dimensions suitable for aerosolization
      and deposition in deep regions of the lung following inhalation were produced. In
      conclusion, the developed system turns to be of great potential for the combined
      delivery of the protein and the adsorption promoter in the respiratory tract.

PMID- 16806858
TI  - Review of global regulations concerning biowaivers for immediate release solid
      oral dosage forms.
AB  - The regulations with respect to biowaivers for immediate release (IR) solid oral
      dosage forms in the USA, the EU, Japan and from the World Health Organization
      (WHO) are summarized and compared. Two case studies are presented, one from our
      own files and one from the open literature, showing the similarities and the
      differences among the qualification requirements of the four systems. The
      regulatory experience gained up to now is reviewed and expected future trends are
      discussed.

PMID- 16806859
TI  - The determination of relative path length as a measure for tortuosity in compacts
      using image analysis.
AB  - Tortuosity is defined as the ratio of the actual path length from start to goal
      through the pores to the Euclidean distance (shortest linear distance). However,
      traditional methods to calculate tortuosity, such as the calculation of
      tortuosity out of the results from dissolution experiments, do not determine path
      length directly. In this paper we describe the application of image analysis for
      direct measurement of path length in order to obtain quantitative information on
      tortuosity. Several planes in cubic sodium chloride compacts, made by uni-axial
      compression, were imaged using scanning electron microscopy (SEM). In these
      images the average path length from top-to-bottom and from left-to-right was
      calculated, using the gray-weighted distance transform (GDT). As the direct,
      straight forward path was defined as having a length of unity, the relative path
      length could be taken as a quantitative measure for the tortuosity. The relative
      path length through the pores was found to be 1.4-1.6 and the relative path
      length over the grains was significantly lower (1.0-1.2). In most cases, the
      relative path length through the pores was significantly higher for the compacts
      containing small particles than for the compacts made of large particles. The
      relative path length was also dependent on the direction of the measurement, i.e.
      in the direction of compression of the compact or perpendicular to it. This
      indicates anisotropy in structure with the pores preferentially oriented in the
      direction of compression. It was concluded that this method is a valuable tool
      for the determination of path length in compacts as a direct measure for
      tortuosity. It can also be used to evaluate the anisotropy in structure.

PMID- 16806860
TI  - [A leucocoria in an infant].

PMID- 16806861
TI  - [Medical aspects of commercial air travel].
AB  - A high proportion of commercial plane passengers are children: two million fly
      every year on Air-France airlines. In this field, the physician can be called
      upon to authorize or prohibit travelling. He could take measures or offer his
      services at the request of the cabin staff. The authors review flight physiology
      and stress, their potential effects on healthy children or those with medical
      conditions, and their fitness to fly.

PMID- 16806862
TI  - [Complement factor I deficiency revealed by repeated systemic Streptococcus
      pneumoniae infection].
AB  - Recurrent and serious otitis media, and 2 Streptococcus pneumoniae bacteraemia
      episodes evoked an immune system deficiency in a 6-year-old girl. Upon
      investigation of the complement system, CH50 activity was moderately reduced and
      C4 antigen level was normal contrasting with low C3 antigen level. Factor 1 was
      undetectable. Factor I deficiency is rare, and its diagnosis has important
      practical consequences. Thanks to preventive antibiotic therapy with penicillin V
      and vaccinations against Neisseria meningitidis and S. pneumoniae, life
      expectancy and quality of this child can be significantly improved.

PMID- 16806863
TI  - Pulmonary tumor types induced in Wistar rats of the so-called "19-dust study".
AB  - The incidences of primary lung tumor types histologically diagnosed in 28 groups
      of Wistar rats of the so-called "19-dust study" are described, the total study
      having been already presented by Pott and Roller (Carcinogenicity study with
      nineteen granular dusts in rats. Eur J Oncol, 2005; 10: 249-81). Each exposed
      group was repeatedly instilled intratracheally with a suspension of one type and
      dose of 13 non-mining dusts differing in at least one of the following
      properties: chemical composition, density, specific surface area, and mean
      particle size. Eleven of the 13 dusts were classified as respirable granular bio
      durable particles without known significant specific toxicity (abbreviation of
      the nine-word definition: GBP). In 579 (58%) lungs of 1002 rats which survived
      more than 26 weeks after the first instillation of GBP, at least one primary lung
      tumor type was observed, and in 306 (31%) at least two types. Three benign tumor
      types were diagnosed in the 579 tumor-bearing rats: bronchiolo-alveolar adenoma
      in 46%, cystic keratinizing epithelioma in 53%, and non-keratinizing epithelioma
      in 2.6% of the rats. Two of three malignant tumor types (bronchiolo-alveolar
      carcinoma and squamous cell carcinoma) occurred in 46% and 31% of the tumor
      bearing rats, respectively, and adenosquamous carcinoma was diagnosed in 0.9%.
      Numerous lungs with a malignant tumor also showed one or more benign tumor types.
      In addition, single or multiple metastases from primary tumors of other sites
      (mainly carcinoma of the uterus) were diagnosed in 14% of the 1002 lungs. The
      proportionate incidences of the four predominantly diagnosed tumor types were
      compared with three summarized experimental groups which were exposed either to
      carbon black (two size classes), to titanium dioxide (two size classes), or to
      the total of the other nine GBP. A significant difference was not detected. The
      combination of dust volume with particle size correlated best with the
      carcinogenic effect, in contrast to dust mass and surface area.

PMID- 16806864
TI  - Indole-3-carbinol alters placental cytochrome P450 1A1 and P-glycoprotein levels
      in rats: a potential role in intensifying fetal intrauterine growth-retardation
      produced by tobacco smoke.
AB  - To investigate the deleterious effects and possible mechanism of prenatal indole
      3-carbinol (I3C) treatment on normal and tobacco-induced intrauterine growth
      restriction (IUGR) in rats, prenatal development toxicity in rats was studied.
      Expression of rat placental cytochrome P4501A1 (CYP1A1) and P-glycoprotein (Pgp),
      including mdr1a and mdr1b, were detected using reverse transcription-polymerase
      chain reaction (RT-PCR) and immunohistochemistry. Results showed that prenatal
      oral I3C had no significant effects on corpora lutea counts, implantation or the
      number of live, dead and resorbed fetuses in normal rats. Fetal malformations,
      sex ratio, neonatal body weights and physical developmental indices were also
      unchanged after prenatal I3C treatment. However, the offspring in the tobacco +
      I3C (4 mg kg(-1)) group showed lower average body weights (3.98+/-0.29 g) than
      tobacco control (4.48+/-0.11 g), and body and tail lengths lagged significantly
      behind those of the tobacco-smoke exposure only group. Expression of placental
      CYP1A1 mRNA by RT-PCR was not detected in the normal group, but was detected in
      the I3C, tobacco and tobacco + I3C groups. The level of CYP1A1 mRNA expression in
      the tobacco + I3C group was higher than in tobacco control. The level of mdr1a
      mRNA increased significantly in the I3C group when compared to normal control,
      and no obvious difference was detected between tobacco and tobacco + I3C groups.
      Expression of mdr1b mRNA was increased in the I3C and tobacco + I3C groups
      compared to their respective controls. Immunohistochemistry results showed that
      placental Pgp expression was enhanced in the I3C, tobacco and tobacco + I3C
      groups when compared to the normal control. The results suggest that prenatal
      oral I3C had no developmental toxicity but intensified fetal IUGR produced by
      prenatal tobacco-smoke exposure in rats. Up-regulations of placental CYP1A1 and
      Pgp by I3C might underlie the toxic mechanism.

PMID- 16806865
TI  - Relationships between renal morphology and diet in 26 species of new world bats
      (suborder microchiroptera).
AB  - The renal morphology of 24 species of mormoopid and phyllostomid bats feeding on
      six different diets was examined to test evolutionary changes in several
      structural traits presumably led by dietary shifts from ancestral insectivorous
      diets. The kidneys of a fish-eating vespertilionid and an insect-eating
      emballonurid were also examined but not included in the phylogenetic comparison.
      The length, width, and breadth of the kidneys were used to calculate relative
      medullary thickness (RMT). Tissues were processed for stereological analysis, and
      the volumes of the kidney, nephron components, and vasculature were determined.
      RMT did not correlate with body mass in either animal-eating or plant-eating
      phyllostomid and mormoopid bats. The shift from insectivory to frugivory and
      nectarivory was accompanied by a reduction in RMT, a reduction in the percent of
      renal medulla, and an increase in the percent of renal cortex. No changes in
      these traits were observed in bats that shifted to carnivorous, omnivorous or
      sanguinivorous habits. No changes were observed in renal vasculature, in the
      percentage of cortical and medullary nephron components or of capillaries
      surrounding the nephrons in any feeding group. Vespertilionid and emballonurid
      species had similar values in all traits examined as compared to insectivorous
      phyllostomids and mormoopids. Our data suggest that diet does not influence a
      single area of the nephron, but rather the entire nephron such that the relative
      amounts of renal cortex and medulla are affected.

PMID- 16806866
TI  - Changes in the patterning of a hydroid colony.
AB  - It is a widely held view that colonial hydroids (Cnidaria, Hydroidomedusae) are
      formed on the basis of a repetition of uniform elements. The dominant opinion is
      that the equal spatial organisation of the colony exists during all stages of its
      development except the primary polyp, which develops from the settled larva.
      However, the complex structure and large dimensions of shoots in certain thecate
      species (subcl. Leptomedusae) suggest that the organisation of the primary shoot
      differs strongly from that of established colonies. The present study based on a
      thorough collection and examination of the collected material allowed to describe
      the entire sequence of the colony ontogeny in Hydrallmania falcata
      (Sertulariidae). The established shoots of this species are characterised by
      relatively large size, spiral arrangement of pinnate branches over the shoot
      stem, and hydranths arranged in one row along the upper side of branches. We
      showed that the primary shoot developing from the larva has much smaller
      dimensions and an alternate arrangement of hydranths. During further colony
      development the shoot organisation undergoes a gradual transformation ending with
      the emergence of large shoots with 'characteristic' species-specific features.
      The discovered sequence of changes in shoot patterning shows certain correlations
      with alterations of the growing tip dimensions. The dimensions of the growing tip
      seem to determine the patterning in accordance with the particular spatial
      location of the tip. This finding implies the necessity of a detailed
      reinvestigation of the entire colony development in thecate hydroids, which would
      make a significant contribution to the understanding of the morphogenetic
      evolution and patterning mechanisms within this group of colonial organisms.

PMID- 16806867
TI  - The discoidin domain receptor DDR2 is a receptor for type X collagen.
AB  - During endochondral ossification, collagen X is deposited in the hypertrophic
      zone of the growth plate. Our previous results have shown that collagen X is
      capable of interacting directly with chondrocytes, primarily via integrin
      alpha2beta1. In this study, we determined whether collagen X could also interact
      with the non-integrin collagen receptors, discoidin domain receptors (DDRs), DDR1
      or DDR2. The widely expressed DDRs are receptor tyrosine kinases that are
      activated by a number of different collagen types. Collagen X was found to be a
      much better ligand for DDR2 than for DDR1. Collagen X bound to the DDR2
      extracellular domain with high affinity and stimulated DDR2 autophosphorylation,
      the first step in transmembrane signalling. Expression of DDR2 in the epiphyseal
      plate was confirmed by RT-PCR and immunohistochemistry. The spatial expression of
      DDR2 in the hypertrophic zone of the growth plate is consistent with a
      physiological interaction of DDR2 with collagen X. Surprisingly, the discoidin
      domain of DDR2, which fully contains the binding sites for the fibrillar
      collagens I and II, was not sufficient for collagen X binding. The nature of the
      DDR2 binding site(s) within collagen X was further analysed. In addition to a
      collagenous domain, collagen X contains a C-terminal NC1 domain. DDR2 was found
      to recognise the triple-helical region of collagen X as well as the NC1 domain.
      Binding to the collagenous region was dependent on the triple-helical
      conformation. DDR2 autophosphorylation was induced by the collagen X triple
      helical region but not the NC1 domain, indicating that the triple-helical region
      of collagen X contains a specific DDR2 binding site that is capable of receptor
      activation. Our study is the first to describe a non-fibrillar collagen ligand
      for DDR2 and will form the basis for further studies into the biological function
      of collagen X during endochondral ossification.

PMID- 16806868
TI  - Regulation of serine protease inhibitor-E2 and plasminogen activator expression
      and secretion by follicle stimulating hormone and growth factors in non
      luteinizing bovine granulosa cells in vitro.
AB  - During ovarian follicle growth, there is expansion of the basal lamina and
      changes in the follicular extracellular matrix (ECM) that are mediated in part by
      proteolytic enzyme cascades regulated by tissue-type plasminogen activator (tPA)
      and urokinase plasminogen activator (uPA). One PA inhibitor, serine protease
      inhibitor-E2 (SERPINE2) is expressed in granulosa but not theca cells, and
      expression changes with follicle development. In this study, we hypothesized that
      PA and SERPINE2 expression/secretion by granulosa cells are regulated by FSH and
      growth factors. SERPINE2 mRNA and protein levels, tPA gene expression and uPA
      secretion were stimulated by FSH. Insulin-like growth factor-I stimulated
      SERPINE2 secretion and uPA activity, and decreased secreted tPA activity and gene
      expression. Bone morphogenetic protein-7 increased SERPINE2 secretion and
      expression and tPA secretion. In contrast, fibroblast growth factor-2 inhibited
      tPA secretion and SERPINE2 secretion and expression. Epidermal growth factor
      inhibited SERPINE2 secretion and expression, but increased secreted tPA activity.
      Estradiol and SERPINE2 secretion were highly positively correlated, but estradiol
      did not alter SERPINE2 expression. These data demonstrate that SERPINE2
      expression and protein secretion are regulated by FSH and growth factors in non
      luteinizing bovine granulosa cells. As estradiol is a known marker of follicle
      health, and SERPINE2 is an anti-apoptotic factor, we propose that SERPINE2 is
      involved in the regulation of atresia in bovine follicles.

PMID- 16806869
TI  - Testican-1 is dispensable for mouse development.
AB  - Testicans are proteoglycans belonging to the BM-40/SPARC/osteonectin family of
      extracellular calcium-binding proteins. Testican-1 is strongly expressed in the
      brain and has been reported to modulate neuronal attachment and matrix
      metalloproteinase activation. Characterization of the mouse testican-1 gene
      (Ticn1), consisting of 12 exons out of which exon 3 is alternatively spliced,
      allowed the construction of a gene targeting construct. Mice deficient in
      testican-1 showed no obvious morphological or behavioral abnormalities, were
      fertile, and had normal life spans. Despite the fact that neither of the testican
      1 homologues expressed in the brain, testican-2, testican-3 and SC1/hevin, showed
      an increased expression in Ticn1 null mice, these results, together with those
      from other gene targetings, indicate extensive functional redundancy among brain
      proteoglycans.

PMID- 16806870
TI  - Gastric mucosal cell model for estimating relative gastrointestinal toxicity of
      non-steroidal anti-inflammatory drugs.
AB  - The study objective was to characterize the AGS human gastric mucosal cell line
      as a model for estimating gastrointestinal toxicity of COX-inhibiting compounds.
      Rofecoxib, celecoxib, nimesulide, ibuprofen, indomethacin, aspirin, salicylic
      acid, naproxen and acetaminophen were tested for inhibition of COX-2-mediated
      prostaglandin E2 synthesis in A549 and AGS cells. The IC50 ratio AGS/A549 was
      calculated as an estimate of the therapeutic index (TI) for gastrointestinal
      toxicity. Calculated IC50 values of non-steroidal anti-inflammatory drugs
      (NSAIDs) in A549 cells were in excellent agreement with published values (r =
      0.996; P < 0.005). Calcium ionophore induction of arachidonic acid release in AGS
      cells provided TI similar to those using platelets and A549 cells (r = 0.918; P <
      0.01). The AGS/A549 model exhibited lower TI than the platelet/A549 model.
      Spearman ranking correlated clinical NSAID gastropathy with lower AGS TI values.
      The AGS cell line has excellent potential to serve as a model for assessing the
      gastrointestinal effects of COX-inhibiting compounds.

PMID- 16806871
TI  - The bioavailability and pharmacodynamics of different concentrations of omega-3
      acid ethyl esters.
AB  - Omega-3 fatty acids have a long history of use as dietary supplements and more
      recently for therapeutic applications as prescription pharmaceuticals. Achieving
      a high concentration is critical for developing convenient, practical therapeutic
      formulations. The objective of the study was to explore the uptake and effects of
      different concentrations of omega-3 acid ethyl esters. Three different omega-3
      concentrations were investigated in a clinical study with 101 subjects. All
      participants were dosed for 14 days with 5.1g per day of eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) ethyl esters provided in three
      concentrations: 62.5%, 80% and 85% of total fatty acids. Key endpoints of the
      study were serum phospholipids and standard fasting lipid panels at day 14.
      Although administered the same quantity of omega-3 fatty acids, the patients
      taking the more concentrated formulations had higher levels of EPA/DHA in serum
      phospholipids and greater reductions in serum triglyceride and VLDL cholesterol
      levels. Total and non-HDL cholesterol were significantly reduced from baseline
      with all three formulations. In conclusion the concentration of omega-3 fatty
      acids of the formulations studied had independent effects on the uptake and
      effect outcomes during short-term administration. Very high concentrations of
      omega-3 acid ethyl esters (80%) appear to have higher uptake and are more potent
      for reducing triglycerides (TGs) and VLDL-cholesterol than formulations with
      lower concentrations.

PMID- 16806873
TI  - Comparison of the Sit-to-Stand Test with 6 min walk test in patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To discuss the utility of Sit-to-Stand Test (STST) compared to the
      6min walking test (6MWT) for the evaluation of functional status in patients with
      chronic obstructive pulmonary disease (COPD). MATERIAL-METHOD:  SUBJECTS: Fifty
      three patients with stable COPD (mean forced expiratory volume in 1s (FEV(1))
      46+/-9% predicted, mean age 71+/-12 year) and 15 healthy individuals (mean FEV(1)
      101+/-13% predicted and mean age 63+/-8) were included. INTERVENTIONS: Functional
      performance was evaluated by STST and 6MWT. During the tests, severity of dyspnea
      (by Modified Borg Scale), heart rate, pulsed oxygen saturation (SpO(2), by
      Modified Borg Scale) (by pulse oxymeter), blood pressure were measured. The
      pulmonary function (by spirometry), quadriceps femoris muscle strength (by manual
      muscle test) and quality of life (by Nottingham Health Profile Survey) were
      evaluated. RESULTS: The STST and 6MWT results were lower in COPD group than the
      healthy group (P<0.05). During the 6MWT the rise in the heart rate, systolic
      blood pressure and the decrease in SpO(2) were statistically significant
      according to STST in COPD groups (P<0.05). The STST and 6MWT were strongly
      correlated with each other in both groups (P<0.05). Similarly, they were
      correlated with age, quality of life, peripheral muscle strength and dyspnea
      severity in COPD groups (P<0.05). CONCLUSION: Similar to 6MWT, STST is also able
      to determine the functional state correctly. Additionally, it produces less
      hemodynamical stress compared to the 6MWT. In conclusion, STST can be used as an
      alternative of the 6MWT in patients with COPD.

PMID- 16806874
TI  - Total lung lavage by awake flexible fiberoptic bronchoscope in a 13-year-old girl
      with pulmonary alveolar proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare, heterogeneous diffuse lung
      disease in childhood. We report a case of an asymptomatic 13-year old girl with
      PAP. She had radiolographic findings suggesting the diagnosis, which was
      confirmed by the "milky" bronchoalveolar lavage fluid and the histology of
      transbronchial biopsy. Total lung lavage was performed by flexible fiberoptic
      bronchoscope under local anesthesia with success. This is the first reported case
      of a PAP in a child that was treated by being awake during bronchoscopy. After
      one-year of follow-up, the patient remains free of symptoms.

PMID- 16806875
TI  - Assessing the usefulness of outcomes measured in a cystic fibrosis treatment
      trial.
AB  - Forced expiratory volume in 1s (FEV(1)) is the usual primary outcome variable in
      clinical trials in cystic fibrosis (CF). Usually, several secondary outcomes are
      also measured. We assessed which secondary outcomes are likely to give additional
      clinically useful information about treatment effects, in order to inform the
      design of future studies. The study was performed as part of a trial comparing
      daily rhDNase with alternate day rhDNase and hypertonic saline in CF. The primary
      outcome was FEV(1). Secondary outcomes were forced vital capacity (FVC), forced
      expiratory flow at 25-75% of forced vital capacity (FEF(25-75)), number of
      pulmonary exacerbations, weight gain, quality of life (QOL), and exercise
      tolerance. The usefulness of each secondary outcome was investigated by assessing
      if the change in that outcome over the treatment period could be predicted from
      the primary outcome. Change in FEV(1) correlated with changes in FVC (r(2)=0.76,
      P=0.001), FEF(25-75) (r(2)=0.64, P=0.001), weight (r(2)=0.08, P=0.001), and
      change in oxygen saturation with exercise (r(2)=0.08, P=0.001). However, it did
      not correlate with changes in visual analogue score (VAS) with exercise, QOL, nor
      with the occurrence of pulmonary exacerbations. Only the outcomes QOL and VAS
      with exercise actually provided additional information to FEV(1) in this study.

PMID- 16806876
TI  - The dose-response characteristics of inhaled corticosteroids when used to treat
      asthma: an overview of Cochrane systematic reviews.
AB  - Inhaled corticosteroids form the cornerstone of treatment for most patients with
      asthma. A range of compounds are available with a wide range of prescribable
      doses. In this overview, we summarize the findings from a number of Cochrane
      systematic reviews that have examined the relative benefits of different doses of
      beclometasone dipropionate, budesonide and fluticasone propionate when used to
      treat children and adults. The key findings are that all inhaled corticosteroids
      demonstrate a dose-response relationship for efficacy measures, but most of the
      benefit in mild-to-moderate severity disease is gained in the low-to-moderate
      dose range of each drug. In this group, high doses of fluticasone lead to small
      improvements in measures of control at the expense of a steep increase in the
      incidence of oral side-effects. In patients with severe disease who are dependent
      on oral steroids, there may be appreciable benefit in reducing oral steroids from
      very high compared with high doses of fluticasone.

PMID- 16806877
TI  - Endosome dynamics during development.
AB  - Endocytosis has traditionally been studied in isolated cells. More recently,
      however, the analysis of protein trafficking in whole organisms has revealed that
      it plays exciting roles during development. Endocytic trafficking of cell
      adhesion molecules regulates epithelial polarity and cell migration.
      Developmental signaling pathways are regulated by the trafficking of receptors
      and their ligands through the endocytic pathway. Finally, impairment of the
      endocytic machinery can affect proliferation control and contribute to tumor
      development.

PMID- 16806879
TI  - Intracellular sterol transport and distribution.
AB  - Sterols are important components of many biological membranes, and changes in
      sterol levels can have dramatic effects on membrane properties. Sterols are
      transported rapidly between cellular organelles by vesicular and nonvesicular
      processes. Recent studies have identified transmembrane proteins that facilitate
      the removal of sterols from membranes as well as soluble cytoplasmic proteins
      that play a role in their movement through the cytoplasm. The mechanisms by which
      these proteins work are generally not well understood. Cells maintain large
      differences in the sterol:phospholipid ratio in different organelles. Recent
      theoretical and experimental studies indicate ways in which the lipid environment
      can alter the chemical potential of sterols, which may help to explain aspects of
      their transport kinetics and distribution.

PMID- 16806880
TI  - Inter-organelle membrane contact sites: through a glass, darkly.
AB  - Inter-organelle membrane contact sites are zones where heterologous membranes,
      usually the endoplasmic reticulum plus a partner organelle, come into close
      apposition. These sites are very poorly understood because so few of their
      components have been identified; however, it is clear that they are specialised
      for traffic of material and information between the two membranes. There have
      been recent advances in the study of lipid transfer proteins, such as ceramide
      transfer protein (CERT) and homologues of oxysterol binding protein (OSBP). Not
      only can these proteins carry lipids across the cytoplasm, but they have been
      found to target both the endoplasmic reticulum and a partnering organelle, and in
      some cases have been localised to membrane contact sites. Further work will be
      needed to test whether these lipid transfer proteins act when anchored at inter
      organelle contact sites.

PMID- 16806881
TI  - A pre-synaptic to-do list for coupling exocytosis to endocytosis.
AB  - Synaptic vesicles are made locally in the nerve terminal during recycling of
      membrane. Synaptic vesicle proteins must be sorted and concentrated on the plasma
      membrane, packaged into a budding vesicle of precise size and cut away from the
      synaptic surface. Adaptors, scaffolds, BAR-domain and ENTH-domain proteins all
      must be coordinated to carry out this sequence of events prior to the action of
      dynamin. Details of how this is orchestrated at nerve terminals are just
      beginning to emerge.

PMID- 16806882
TI  - Biogenesis of secretory granules.
AB  - Secretory granules of neuroendocrine cells store and release peptide hormones and
      neuropeptides in response to various stimuli. Generation of granules from the
      Golgi complex involves the aggregation of cargo proteins and their sorting from
      non-regulated secretory molecules. Recent findings on knockout mice lacking
      individual granule constituents have challenged the hypothesis that an
      'essential' protein for the assembly of these organelles exists, while studies on
      polypyrimidine tract-binding protein and ICA512/IA-2 have provided insight into
      the mechanisms for adjusting granule production in relation to stimulation and
      secretory activity.

PMID- 16806884
TI  - Molecular structures of coat and coat-associated proteins: function follows form.
AB  - Endocytic clathrin-coated vesicles arise through the deformation of a small
      region of plasma membrane encapsulated by a cytosol-oriented clathrin lattice.
      The coat assembles from soluble protomers in a rapid and highly cooperative
      process, and invagination is tightly linked to the selective enrichment of cargo
      molecules within the nascent bud. Recent structural and functional studies
      demonstrate that coat assembly, membrane deformation, local actin dynamics and
      the final scission event are intricately coupled, and begin to reveal how key
      multifunctional, modular proteins are responsible for this linkage. An emerging
      mechanistic theme is how sequential engagement of common interaction surfaces or
      network hubs can evict prior binding partners from the assembly zone to ensure
      vectorial progression of the coat assembly process.

PMID- 16806885
TI  - Developing a master plan for hospital solid waste management: a case study.
AB  - Disposal of about 1750tons of solid wastes per day is the result of a rapid
      population growth in the province of Khuzestan in the south west of Iran. Most of
      these wastes, especially hospital solid wastes which have contributed to the
      pollution of the environment in the study area, are not properly managed
      considering environmental standards and regulations. In this paper, the framework
      of a master plan for managing hospital solid wastes is proposed considering
      different criteria which are usually used for evaluating the pollution of
      hospital solid waste loads. The effectiveness of the management schemes is also
      evaluated. In order to rank the hospitals and determine the share of each
      hospital in the total hospital solid waste pollution load, a multiple criteria
      decision making technique, namely analytical hierarchy process (AHP), is used. A
      set of projects are proposed for solid waste pollution control and reduction in
      the proposed framework. It is partially applied for hospital solid waste
      management in the province of Khuzestan, Iran. The results have shown that the
      hospitals located near the capital city of the province, Ahvaz, produce more than
      43% of the total hospital solid waste pollution load of the province. The results
      have also shown the importance of improving management techniques rather than
      building new facilities. The proposed methodology is used to formulate a master
      plan for hospital solid waste management.

PMID- 16806883
TI  - Endoplasmic reticulum architecture: structures in flux.
AB  - The endoplasmic reticulum (ER) is a dynamic pleiomorphic organelle containing
      continuous but distinct subdomains. The diversity of ER structures parallels its
      many functions, including secretory protein biogenesis, lipid synthesis, drug
      metabolism and Ca2+ signaling. Recent studies are revealing how elaborate ER
      structures arise in response to subtle changes in protein levels, dynamics, and
      interactions as well as in response to alterations in cytosolic ion
      concentrations. Subdomain formation appears to be governed by principles of self
      organization. Once formed, ER subdomains remain malleable and can be rapidly
      transformed into alternative structures in response to altered conditions. The
      mechanisms that modulate ER structure are likely to be important for the
      generation of the characteristic shapes of other organelles.

PMID- 16806886
TI  - Sub-second adsorptive fast Fourier transform coulometric technique as a novel
      method for the determination of nanomolar concentrations of sodium valproate in
      its pharmaceutical preparation in flowing solution systems.
AB  - In this work, a novel electrochemical technique has been developed for
      determination of nanomolar concentration of sodium valproate in flow-injection
      systems. The detection was done by adsorptive fast Fourier transform coulometric
      (AFFTC), in which the potential waveform consists of potential steps for
      cleaning, accumulation, and a potential ramp that was continuously applied on an
      Au disk microelectrode. Moreover, a special computer program is introduced based
      on numerical method, for calculation of the analyte signal (which is the partial
      and total charge exchanges at the electrode surface) and noise reduction. The
      optimum parameters were: pH value of 2.0, scan rate value of 40 Vs(-1),
      accumulation potential of 200 mV and accumulation time of 0.3 s. Detection limit
      of the method for sodium valproate was 9.0x10(-9) M. The relative standard
      deviation of the method at 1.3x10(-7) M was 2.0% for 10 runs.

PMID- 16806887
TI  - Building of an immunosensor: how can the composition and structure of the thiol
      attachment layer affect the immunosensor efficiency?
AB  - Immunosensors, based on the immobilization of a model rabbit antibody on mixed
      self-assembled monolayers and Protein A as a linking agent on gold transducers,
      were elaborated and characterized at each step by modulated polarization-infrared
      spectroscopy (PM-IRRAS) and occasionally by atomic force microscopy (AFM) and
      quartz crystal microbalance (QCM). By testing two different mixed SAMs comprising
      11-mercaptoundecanoic acid (MUA), together with either decanethiol (C9CH3) or
      mercaptohexanol (C6OH), the role of the chemical composition and structure of the
      antibody attachment layer upon the sensor performance was demonstrated.

PMID- 16806888
TI  - Amperometric tyrosinase biosensor based on polyacrylamide microgels.
AB  - An amperometric enzyme sensor using tyrosinase (PPO) entrapped in polyacrylamide
      microgels has been developed for determination of phenolic compounds.
      Polyacrylamide microgels were obtained by the concentrated emulsion
      polymerization method. The crosslinking of the polymer matrix optimum to retain
      the enzyme and to allow the diffusion of the compounds involved in the enzyme
      reaction has been studied (4.0%) as well as the influence on the response of
      analytical parameters such as pH, temperature, enzyme load and working potential.
      The useful lifetime of the biosensor was 27 days and it was useful to determine
      monophenolics compounds (e.g. cresol, chlorophenol) and diphenolics compounds
      (e.g. catechol and dopamine) by amperometric measurements at -100mV (versus SCE)
      in a batch system. The results showed that the substrate structures have a great
      influence on the sensor response.

PMID- 16806889
TI  - Electrochemically amplified detection for lipopolysaccharide using
      ferrocenylboronic acid.
AB  - A novel electrochemical technique for lipopolysaccharide (LPS) detection has been
      developed using a combination of ferrocenylboronic acid derivatives and an enzyme
      modified electrode. The enzyme-modified electrode was constructed from a gold
      electrode modified with a bovine serum albumin membrane containing diaphorase.
      Ferrocenylboronic acid derivatives are oxidized on the electrode, and then
      regenerated by a diaphorase-catalyzed reaction in the presence of NADH. The
      consumption/regeneration cycle for ferrocenylboronic acid derivatives resulted in
      a chemically amplified current response. The current response for
      ferrocenylboronic acid derivatives decreased in association with its complexation
      with glycosyl units of LPS, and this current decrease caused by LPS was also
      amplified by the recycling process. On the other hand, the addition of a
      monosaccharide such as D-mannose or D-galactose induced no response at the same
      LPS concentration. The enzyme membrane immobilized on the electrode plays an
      important role in selectivity as well as chemical amplification. In addition, the
      enzyme-modified electrode exhibited a rapid response of 5 min for LPS, which is
      much faster than the currently used method. The detection limit of LPS from
      Escherichia coli O127:B8 was as low as 50 ng ml-1.

PMID- 16806890
TI  - Towards the design of highly selective recognition sites into molecular
      imprinting polymers: a computational approach.
AB  - A computational approach to simulate the formation of possible imprinted polymers
      in acetonitrile solution for theophylline (THO) is proposed, using combined
      molecular dynamics (MD), molecular mechanics (MM), docking and site mapping
      computational techniques. Methacrylic acid (MAA) and methylmethacrylate (MMA)
      monomers are used to simulate possible homo and copolymer structures. The model
      is able predict binding affinity and selectivity when considering THO analogues,
      such as caffeine, theobromine, xanthine and 3-methylxanthine. Comparison with
      available experimental data is proposed.

PMID- 16806891
TI  - Investigation into the effect that probe immobilisation method type has on the
      analytical signal of an EIS DNA biosensor.
AB  - The analytical performance of an enhanced surface area electrolyte insulator
      semiconductor (EIS) device was investigated for DNA sensor development. The work
      endeavored to advance EIS performance by monitoring the effect of DNA probe
      layers have on the impedimetric signal during target hybridisation detection. Two
      universally employed covalent chemistries, direct and spacer-mediated attachment
      of amino modified probe molecules to amino-functionalised surfaces were
      investigated. Relative areal densities of immobilised probe were measured on
      planar and enhanced surface area substrates using epi-fluorescence microscopy.
      The reproducibility of the each immobilisation method was seen to have a direct
      effect on the reproducibility of the impedimetric signal. The sensitivity and
      selectivity was seen to be dependent on the type of immobilisation method. Real
      time, impedimetric detection of target DNA hybridisation concentrations as low as
      25 and 1 nM were possible. The impact that probe concentration had on the
      impedimetric signal for selective and non-selective interactions was also
      investigated.

PMID- 16806892
TI  - Yeast two-hybrid contributions to interactome mapping.
AB  - Interactome mapping, the systematic identification of protein interactions within
      an organism, promises to facilitate systems-level studies of biological
      processes. Using in vitro technologies that measure specific protein
      interactions, static maps are being generated that include many of the protein
      networks that occur in vivo. Most of the binary protein interaction data
      currently available was generated by large-scale yeast two-hybrid screens. Recent
      efforts to map interactions in model organisms and in humans illustrate the
      promise and some of the limitations of the two-hybrid approach. Although these
      maps are incomplete and include false positives, they are proving useful as a
      framework around which to elaborate and model the in vivo interactome.

PMID- 16806893
TI  - Mammalian cell factories for efficient and stable protein expression.
AB  - As the commercial market for therapeutic protein production from mammalian cells
      has expanded, so has the requirement for improved efficiency and stability of
      production. Rapid developments have been made in understanding the molecular
      environment of transgenes in chromatin, including elucidation of the contribution
      of epigenetic modifications to expression, and this understanding is being used
      to enhance expression from host cells. Technical advances surrounding the 'omics'
      revolution are enabling the rational identification of complex control factors
      that define the flow of information from transgene to desired protein. Using
      information from 'omics' interrogations, directed cell engineering has been
      employed to enhance the translational and secretory capacity of host cells. Taken
      together, these recent advances are likely to lead to improved routes for protein
      production in the future.

PMID- 16806894
TI  - Phosphoproteomic approaches to elucidate cellular signaling networks.
AB  - Protein phosphorylation is crucial in the regulation of signaling pathways that
      control various biological responses. Recent progress in diverse methodologies to
      investigate protein phosphorylation in complex biological samples has resulted in
      more rapid, detailed and quantitative analyses of signaling networks. In
      particular, advances in mass spectrometry (MS) have enabled the identification
      and quantification of thousands of both known and novel phosphorylation sites.
      Initial MS-based information can be complemented with a variety of recently
      developed and improved phosphoproteomic techniques. These include multiplexed
      microbead or kinase activity assays, flow cytometry based single-cell analysis,
      protein microarrays and interaction studies. The combination of multiple
      approaches, coupled with phenotypic response measurements, computational modeling
      and biochemical manipulations, will ultimately reveal the mechanistic regulation
      of signaling networks.

PMID- 16806895
TI  - Feedback signaling controls leading-edge formation during chemotaxis.
AB  - Chemotactic cells translate shallow chemoattractant gradients into a highly
      polarized intracellular response that includes the localized production of
      PI(3,4,5)P(3) on the side of the cell facing the highest chemoattractant
      concentration. Research over the past decade began to uncover the molecular
      mechanisms involved in this localized signal amplification controlling the
      leading edge of chemotaxing cells. These mechanisms have been shown to involve
      multiple positive feedback loops, in which the PI(3,4,5)P(3) signal amplifies
      itself independently of the original stimulus, as well as inhibitory signals that
      restrict PI(3,4,5)P(3) to the leading edge, thereby creating a steep
      intracellular PI(3,4,5)P(3) gradient. Molecules involved in positive feedback
      signaling at the leading edge include the small G-proteins Rac and Ras,
      phosphatidylinositol-3 kinase and F-actin, as part of interlinked feedback loops
      that lead to a robust production of PI(3,4,5)P(3).

PMID- 16806896
TI  - The first cell-fate decisions in the mouse embryo: destiny is a matter of both
      chance and choice.
AB  - Development of the early mouse embryo has always been classified as regulative,
      meaning that when parts or blastomeres of the embryo are isolated they change
      their developmental fate and can even reconstruct the whole. However, regulative
      development does not mean that, in situ, these parts or blastomeres are
      equivalent; it does not mean that the early mammalian embryo is a ball of
      identical cells without any bias. Regulative development simply means that
      whatever bias the regions of the embryo might have they still remain flexible and
      can respond to experimental interference by changes of fate. This realization --
      that regulative development and patterning can co-exist -- has led to a
      renaissance of interest in the first days of development of the mouse embryo, and
      several laboratories have provided evidence for some early bias. Now the
      challenge is to gain some understanding of the molecular basis of this bias.

PMID- 16806897
TI  - Attraction rules: germ cell migration in zebrafish.
AB  - The migration of zebrafish primordial germ cell towards the region where the
      gonad develops is guided by the chemokine SDF-1a. Recent studies show that soon
      after their specification, the cells undergo a series of morphological
      alterations before they become motile and are able to respond to attractive cues.
      As migratory cells, primordial germ cells move towards their target while
      correcting their path upon exiting a cyclic phase in which morphological cell
      polarity is lost. In the following stages, the cells gather at specific locations
      and move as cell clusters towards their final target. In all of these stages,
      zebrafish germ cells respond as individual cells to alterations in the shape of
      the sdf-1a expression domain, by directed migration towards their target - the
      position where the gonad develops.

PMID- 16806898
TI  - Mechanistic insight into how Shh patterns the vertebrate limb.
AB  - The hands and feet of a newborn baby are a beautiful reminder of the complexity
      of embryonic patterning. Classical studies on how these structures form have led
      to a theoretical framework for understanding, in general, how discrete groups of
      cells can instruct differential fates across a wider field through the action of
      long-range signals. The discovery just more than a decade ago that localized
      expression of Sonic hedgehog (Shh) differentially patterns structures across the
      limb field, resulting in digits with unique characteristics, provided a starting
      point for readdressing these models at a molecular level. Current research has
      revealed unexpected complexity in how a gradient of Shh activity is both
      established and received, prompting re-evaluation of the nature of patterning
      mechanisms within the limb.

PMID- 16806899
TI  - Follow the fatty brick road: lipid signaling in cell migration.
AB  - Lysophospholipids play important roles in the migration of lymphocytes, smooth
      muscle cells and germ cells in vertebrates and invertebrates. In vertebrates, the
      migratory responses are mediated by specific G-protein-coupled receptors. These
      are expressed in both migrating lymphocyte and smooth muscle cells, and in their
      surrounding cells. In Drosophila germ cell migration, lipid phosphatases also act
      in both the surrounding and the migrating cells. In all three scenarios, the
      contributions of these genes in the stationary and migrating cells are being
      teased apart by genetic studies and direct observation, with exciting results.

PMID- 16806901
TI  - Adjuvant trastuzumab therapy for HER2-overexpressing breast cancer: what we know
      and what we still need to learn.
AB  - With the reporting of five studies with different and complementary designs, but
      all demonstrating a similar and striking benefit from the targeted drug
      trastuzumab in HER2-overexpressing breast cancer, the year 2005 has profoundly
      marked the history of randomised adjuvant breast cancer trials. In view of the
      halving in recurrence risk, obtained at the real but small risk of
      cardiotoxicity, these results are generating hope in women affected with this
      aggressive form of the disease. But at the same time these results pose real
      challenges to healthcare authorities faced with the high cost of the anti-HER2
      monoclonal antibody. These results also leave oncologists and patients to deal
      with a complex treatment tailoring process that needs to take into account risk
      of an early relapse as well as the benefit versus risk of trastuzumab according
      to the different patterns of administration used in the clinical trials.

PMID- 16806902
TI  - The role of complementary and alternative medicine in the management of early
      breast cancer: recommendations of the European Society of Mastology (EUSOMA).
AB  - Patients diagnosed with breast cancer have many needs that for a start include
      the expectation of cure. Where cure is unlikely there is always a place for hope
      and spiritual support. Furthermore whether dealing with the early stages or with
      the advanced disease patients require symptomatic control that encompasses pain
      relief, control of nausea and vomiting and psychological distress. To achieve all
      of these goals there is a need that goes beyond the role of scientific medicine.
      This position papers describes the guidelines for the use of complimentary and
      alternative medicine (CAM) developed by a workshop on behalf of the European
      Society of Mastology (EUSOMA).

PMID- 16806903
TI  - Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus.
AB  - The aims of this study were reviewing our experience regarding the pulmonary
      toxicity of the mammalian target of rapamycin (mTOR) inhibitor temsirolimus,
      discussing potential pathogenic mechanisms and proposing management strategies.
      Medical records and radiological reports of 22 patients treated with weekly doses
      of temsirolimus 25 mg were reviewed. Eight (36%) out of 22 patients developed
      pulmonary abnormalities compatible with drug-induced pneumonitis. Half were
      asymptomatic and in those with symptoms, dyspnea and dry cough were the most
      common. Radiologically two different patterns, ground glass opacities and lung
      parenchymal consolidation, were described. The management of this toxicity was
      variable, ranging from no intervention to discontinuation of the drug. In our
      experience temsirolimus may cause drug-induced pneumonitis at a higher incidence
      than that previously reported. The presentation and its severity are variable.
      The risk of developing this toxicity may be increased among subjects with
      abnormal pre-treatment pulmonary functions or history of lung disease.

PMID- 16806904
TI  - Dutasteride affects progesterone metabolizing enzyme activity/expression in human
      breast cell lines resulting in suppression of cell proliferation and detachment.
AB  - Recent evidence indicates that progesterone metabolites play important roles in
      regulating breast cancer. Previous studies have shown that breast carcinoma and
      tumorigenic breast cell lines have higher 5alpha-reductase and lower 3alpha
      hydroxysteroid oxidoreductase (3alpha-HSO) and 20alpha-HSO activities and mRNA
      expression levels than normal tissue and non-tumorigenic cell lines. The 5alpha
      reduced progesterone metabolites such as 5alpha-dihydroprogesterone (5alphaP)
      promote both mitogenic and metastatic activity in breast cell lines in culture,
      whereas the 4-pregnene metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4
      pregnen-20alpha-ol-3-one (20alphaHP) have the opposite (anti-cancer-like)
      effects. The 5alpha-reductase inhibitor dutasteride has been shown to inhibit
      5alpha-reduction of testosterone to 5alpha-dihydrotestosterone in prostate
      tissue, resulting in decreased prostate volume. The aim of this study was to
      determine if dutasteride is an effective inhibitor of progesterone 5alpha
      reduction in human breast cell lines and if such inhibition reduces mammary cell
      proliferation and detachment. The effect of dutasteride on progesterone
      metabolizing enzyme activities and mRNA expression were examined in tumorigenic
      MCF-7 and non-tumorigenic MCF-10A human breast cell lines. Dutasteride (10(-6)M)
      inhibited progesterone conversion to 5alpha-pregnanes by >95% and increased 4
      pregnene production. The results indicated that effects of dutasteride on the
      progesterone metabolizing enzymes are due to direct inhibition of 5alpha
      reductase activity and to altered levels of expression of 5alpha-reductase and
      HSO mRNAs. Treatment of cells with progesterone without medium change for 72 h
      resulted in significant conversion to 5alpha-pregnanes and increases in cell
      proliferation and detachment. The increases in proliferation and detachment were
      blocked by dutasteride and were reinstated by concomitant treatment with 5alphaP,
      providing proof-of-principle that the effects were due not to progesterone but to
      the 5alpha-reduced metabolites. This study provides the first evidence that
      dutasteride is a potent progesterone 5alpha-reductase inhibitor and that such
      inhibition may be beneficial in breast cancer.

PMID- 16806905
TI  - Comparison of effects of 4-hydroxy tamoxifen and trilostane on oestrogen
      regulated gene expression in MCF-7 cells: up-regulation of oestrogen receptor
      beta.
AB  - 4-Hydroxy tamoxifen (OHT) and trilostane interact differently with the oestrogen
      receptor (ER). OHT is a competitive inhibitor whereas trilostane has direct, but
      non-competitive effects on ER. This study compared the effects of OHT and
      trilostane, in the presence of 17beta-oestradiol (E2) on gene expression in MCF-7
      breast cancer cells using microarrays each representing nearly 20,000 human
      genes. Striking differences between the sets of genes affected by these two drugs
      were observed. Both OHT and trilostane affected transcription of genes involved
      in cell cycle regulation, cell adhesion and matrix formation, however, only 12.5%
      of trilostane down-regulated genes and 9.2% of up-regulated genes were similarly
      regulated by OHT. A selective up-regulation of ERbeta by trilostane, but not OHT,
      was observed and confirmed by qRT-PCR. Similar up-regulation of this gene by
      trilostane was observed in the uterus of trilostane-treated (4 mg/kg for 7 days)
      rats, in which ERbeta mRNA (3-fold) and ERbeta protein expression (10-fold) were
      both increased. These data show that OHT and trilostane regulate the expression
      of different sets of genes, reflecting their different modes of interaction with
      ER. Trilostane-specific up-regulation of ERbeta could explain its positive
      benefit rates in acquired tamoxifen resistance.

PMID- 16806906
TI  - Detection of the Bcl I polymorphism of the glucocorticoid receptor gene by single
      tube allele-specific polymerase chain reaction.
AB  - The Bcl I polymorphism of the glucocorticoid receptor gene, recently identified
      as an intronic C to G change 646 nucleotides downstream of exon 2, has been
      associated with increased sensitivity to glucocorticoids and its potential
      relevance in metabolic disturbances and in various disorders has been extensively
      investigated. In the present study, we designed a single-tube allele-specific
      polymerase chain reaction for genotyping this polymorphism in peripheral blood
      DNA samples. When the Bcl I polymorphism was detected with this novel method in a
      cohort of 247 healthy subjects, the observed genotype distribution matched the
      Hardy-Weinberg equilibrium (100 subjects homozygous for the wild-type, 124
      heterozygous and 23 homozygous for the mutant allele). In 50 randomly selected
      subjects the Bcl I polymorphism was also determined using a traditional
      restriction fragment length polymorphism technique and DNA sequencing, and the
      results showed 100% coincidence with those obtained by our novel method. The
      method proved to be more rapid and less labour-intensive compared to currently
      used techniques, and it avoided the use of extensive instrumentals. We assume
      that this novel method may have a broad utility in clinical and molecular
      epidemiological studies aimed to elucidate the impact of the Bcl I polymorphism
      of the glucocorticoid receptor gene either on metabolic disturbances, or various
      disorders, including cancer treatment and hormone substitution therapies.

PMID- 16806907
TI  - Particleboard quality characteristics of saline jose tall wheatgrass and chemical
      treatment effect.
AB  - The objective of this research was to characterize the qualities (mechanical
      properties and water resistance) of particleboard made from saline Jose Tall
      Wheatgrass (JTW), Agropyron elongatum. For the JTW particleboards made with 4%
      polymeric methane diphenyl diisocyanate (PMDI), the mechanical properties and
      water resistance improved with the increase of particleboard density from 0.71 to
      0.75 g/cm(3). The particleboards with density of 0.74 g/cm(3) had similar
      mechanical properties of wood-based particleboards, except for lower internal
      bond strength. Among the particleboards made with particles of different initial
      moisture contents from 2% to 10%, the particleboard with the particles of 8%
      initial moisture content had the highest qualities. The pretreatment using NaOH
      solution to wash the JTW particles reduced the qualities of finished
      particleboards bonded with both PMDI and urea formaldehyde (UF) resins.
      Particleboards made with PMDI showed superior qualities than those made with UF,
      as shown by the measured contact angle results between the adhesives and JTW.

PMID- 16806908
TI  - Optimization of culture variables for improving glucoamylase production by
      alginate-entrapped Thermomucor indicae-seudaticae using statistical methods.
AB  - Alginate-entrapped sporangiospores of Thermomucor indicae-seudaticae were used
      for the production of glucoamylase. The critical variables that affected
      glucoamylase production were identified by Plackett-Burman design (sucrose, yeast
      extract, K(2)HPO(4) and asparagine) and further optimized by using a four factor
      central composite design (CCD) of response surface methodology (RSM). Immobilized
      sporangiospores secreted 41% and 60% higher glucoamylase titers in shake flasks
      and airlift fermenter, respectively, when the variables were used at their
      optimum levels (sucrose 3.0%, yeast-extract 0.2%, K(2)HPO(4) 0.1% and asparagine
      0.35%). Glucoamylase production (26.3 U ml(-1)) in the optimized medium was in
      good agreement with the values predicted by the quadratic model (26.7 U ml(-1)),
      thereby confirming its validity. The enzyme production was sustainable in flasks
      of higher volume and also airlift fermenter, and attained a peak within 32 h in
      the fermenter as compared to that of 48 h in shake flasks.

PMID- 16806909
TI  - Enhanced production of scleroglucan by Sclerotium rolfsii MTCC 2156 by use of
      metabolic precursors.
AB  - The aim of this work was to study the effect of addition of different amino acids
      and sugar nucleotides as metabolic precursors on the production of scleroglucan.
      A maximum yield of 20.00 g/l and 22.32 g/l was obtained with optimized media
      supplemented with L-lysine (1.1 mM) and uridine mono-phosphate (UMP),
      respectively as compared to 16.52 g/l scleroglucan achieved with the control in
      the absence of metabolic precursors.

PMID- 16806910
TI  - Anaerobic co-digestion of olive mill wastewater with olive mill solid waste in a
      tubular digester at mesophilic temperature.
AB  - Anaerobic co-digestion is a well established process for treating many types of
      organic wastes, both solid and liquid. In this study we have investigated, on a
      laboratory scale, the anaerobic co-digestion of olive mill wastewater (OMW) with
      olive mill solid waste (OMSW) using semi-continuous, feeding, tubular digesters
      operated at mesophilic temperatures. Each digester was fed with an influent,
      composed of OMW and OMSW, at an organic loading rate (OLR) varying between 0.67
      and 6.67 g COD/l/d. The hydraulic retention times (HRT) were 12, 24 and 36 days.
      The TCOD concentrations of OMW used as the main substrate were 24, 56 and 80 g
      COD/l; the amount of the dry OMSW used as a co-substrate was fixed to
      approximately 56 g/l of OMW. The results indicated that the best methane
      production was about 0.95 l/l/day obtained at an OLR = 4.67 g COD/l/d,
      corresponding to influent TCOD = 56 g COD/l at an HRT = 12d. In contrast, the
      maximum TCOD removal efficiency (89%) was achieved at an OLR = 0.67 g COD/l/d,
      corresponding to influent TCOD = 24 g COD/l at an HRT = 36 d. Moreover, the
      inhibition of biogas production was observed at the highest OLR studied.

PMID- 16806911
TI  - Extraction of inhibitor-free metagenomic DNA from polluted sediments, compatible
      with molecular diversity analysis using adsorption and ion-exchange treatments.
AB  - PCR inhibitor-free metagenomic DNA of high quality and high yield was extracted
      from highly polluted sediments using a simple remediation strategy of adsorption
      and ion-exchange chromatography. Extraction procedure was optimized with series
      of steps, which involved gentle mechanical lysis, treatment with powdered
      activated charcoal (PAC) and ion-exchange chromatography with amberlite resin.
      Quality of the extracted DNA for molecular diversity analysis was tested by
      amplifying bacterial 16S rDNA (16S rRNA gene) with eubacterial specific universal
      primers (8f and 1492r), cloning of the amplified 16S rDNA and ARDRA (amplified
      rDNA restriction analysis) of the 16S rDNA clones. The presence of discrete
      differences in ARDRA banding profiles provided evidence for expediency of the DNA
      extraction protocol in molecular diversity studies. A comparison of the optimized
      protocol with commercial Ultraclean Soil DNA isolation kit suggested that method
      described in this report would be more efficient in removing metallic and organic
      inhibitors, from polluted sediment samples.

PMID- 16806912
TI  - Fungicidal property of active component derived from Acorus gramineus rhizome
      against phytopathogenic fungi.
AB  - The fungicidal property of Acorus gramineus rhizome-derived materials against
      Botrytis cineria, Erysiphe graminis, Phytophthora infestans, Puccinia recondita,
      Pyricularia grisea, and Rhizoctonia solani was tested using a whole plant method
      in vivo, and was compared with a synthetic fungicide and seven commercially
      available A. gramineus rhizome-derived components. The responses varied according
      to the plant pathogen tested. At 2000 mg/l, the hexane fraction of A. gramineus
      rhizomes showed strong fungicidal activities against R. solani and P. infestans.
      The results indicated at least one of the fungicidal actions of alpha-asarone and
      asaronaldehyde derived from A. gramineus rhizomes.

PMID- 16806913
TI  - N-Tetrahydroquinolinyl, N-quinolinyl and N-isoquinolinyl biaryl carboxamides as
      antagonists of TRPV1.
AB  - Starting from the high throughput screening hit (3), novel N
      tetrahydroquinolinyl, N-quinolinyl and N-isoquinolinyl carboxamides have been
      identified as potent antagonists of the ion channel TRPV1. The N
      quinolinylnicotinamide (46) showed excellent potency at human, guinea pig and rat
      TRPV1, a favourable in vitro DMPK profile and activity in an in vivo model of
      inflammatory pain.

PMID- 16806914
TI  - Design and synthesis of new water-soluble tetrazolide derivatives of celecoxib
      and rofecoxib as selective cyclooxygenase-2 (COX-2) inhibitors.
AB  - In an attempt to prepare a new water-soluble, parenteral COX-2 inhibitor,
      rofecoxib (9) and celecoxib (13) analogues were designed and synthesized for
      evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo anti
      inflammatory activity. In this experiment, respective SO(2)Me and SO(2)NH(2)
      hydrogen-bonding pharmacophores were replaced by a tetrazole ring. Molecular
      modeling (docking) studies showed that the tetrazole ring of these two analogues
      (9 and 13) was inserted deep into the secondary pocket of the human COX-2 binding
      site where it undergoes electrostatic interaction with Arg(513). The rofecoxib
      (9) and celecoxib (13) analogues exhibited a high in vitro selectivity (9, COX-1
      IC(50) = 3.8 nM; COX-2 IC(50) = 1.8 nM; SI = 2.11; 13, COX-1 IC(50) = 4.1 nM; COX
      2 IC(50) = 1.9 nM; SI = 2.16) relative to the reference drug celecoxib (COX-1
      IC(50) = 3.7 nM; COX-2 IC(50) = .2 nM; SI=1.68) and also showed high aqueous
      solubility at pH higher than 7 and good anti-inflammatory activity in a
      carrageenan-induced rat paw edema assay. However, 9 and 13 had no significant
      damage on gastric mucosa.

PMID- 16806915
TI  - Development of first photoresponsive prodrug of paclitaxel.
AB  - A prodrug of paclitaxel which has a coumarin derivative conjugated to the amino
      acid moiety of isotaxel (O-acyl isoform of paclitaxel) has been synthesized. The
      prodrug was selectively converted to isotaxel by visible light irradiation (430
      nm) with the cleavage of coumarin. Finally, paclitaxel was released by subsequent
      spontaneous O-N intramolecular acyl migration.

PMID- 16806916
TI  - Inhibitors of epidermal growth factor receptor tyrosine kinase: optimisation of
      potency and in vivo pharmacokinetics.
AB  - The structure-activity and structure-property relationships of anilinoquinazoline
      inhibitors of EGFR were investigated. Strategies to lower volume of distribution
      and shorten half-life through structure and pKa modulation are discussed.

PMID- 16806917
TI  - Newly discovered orally active pure antiestrogens.
AB  - In order to develop orally active pure antiestrogens, we incorporated the carboxy
      containing side chains into the 7alpha-position of the steroid scaffold and found
      that 17-keto derivative CH4893237 (12b) functioned as a pure antiestrogen with
      its oral activity much superior to clinically used pure antiestrogen, ICI182,780.
      Results from the pharmacokinetic evaluation indicated that the potent
      antiestrogen activity at oral dosing in mice attributed to both improved
      absorption from the intestinal wall and metabolic stability in liver.

PMID- 16806918
TI  - An efficient one-pot synthesis of octahydroquinazolinone derivatives using
      catalytic amount of H2SO4 in water.
AB  - In this investigation, a practical green chemistry procedure for synthesis of
      octahydroquinazolinone according to the Biginelli reaction using 5,5-dimethyl-1,3
      cyclohexanedione, urea or thiourea, and appropriate aromatic aldehydes in the
      presence of two drops of concentrated H(2)SO(4) as a catalyst is described in
      water. This methodology is of interest due to the use of water as a solvent
      without use of any organic solvent and toxic metals as catalyst, thus minimizing
      the cost, the operational hazards, and environmental pollution. Also this
      modified route provides much higher yields and simple work-up procedure of
      products.

PMID- 16806919
TI  - 4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17beta
      hydroxysteroid dehydrogenase. Part 3. Identification of lead candidate.
AB  - A series of 4,5-disubstituted cis-pyrrolidinones was investigated as inhibitors
      of 17beta-HSD II for the treatment of osteoporosis. Biochemical data for several
      compounds are given. Compound 42 was selected as the lead candidate.

PMID- 16806920
TI  - Monocyclic thiophenes as protein tyrosine phosphatase 1B inhibitors: capturing
      interactions with Asp48.
AB  - A series of monocyclic thiophenes was designed and synthesized as PTP1B
      inhibitors. Guided by X-ray co-crystal structural information and computational
      modeling, rational design led to key interactions with Asp48 and improved
      inhibitory potency against PTP1B.

PMID- 16806921
TI  - Antibacterial activity of pyrrolopyridine-substituted oxazolidinones: synthesis
      and in vitro SAR of various C-5 acetamide replacements.
AB  - A series of pyrrolopyridine-substituted oxazolidinones containing various C-5
      acetamide isosteres was synthesized and the structure-antibacterial activity
      relationships determined against a representative panel of susceptible and
      resistant Gram-positive bacteria.

PMID- 16806922
TI  - Modification of the clozapine structure by parallel synthesis.
AB  - A structure-activity study based on the core structure of clozapine 1b was
      accomplished by utilizing high-throughput synthesis. Several focused libraries
      were designed and synthesized to quickly develop SAR. The results indicate that
      by varying different regions of clozapine, both D(1)-selective and D(2)-selective
      compounds can be obtained.

PMID- 16806923
TI  - Comparative QSAR modeling of CCR5 receptor binding affinity of substituted 1-(3,3
      diphenylpropyl)-piperidinyl amides and ureas.
AB  - The present QSAR study attempts to explore the structural and physicochemical
      requirements of substituted 1-(3,3-diphenylpropyl)-piperidinyl amides and ureas
      for CCR5 binding affinity using linear free energy-related (LFER) model of
      Hansch. QSAR models have been developed using electronic (Hammett sigma),
      hydrophobicity (pi), and steric (molar refractivity and STERIMOL L, B1, and B5)
      parameters of phenyl ring substituents of the compounds along with appropriate
      dummy variables. Whole molecular descriptor like partition coefficient
      (logP(calcd)) was also tried as an additional descriptor. Statistical techniques
      like stepwise regression, multiple linear regression with factor analysis as the
      data preprocessing step (FA-MLR), partial least squares with factor analysis as
      the preprocessing step (FA-PLS), principal component regression analysis (PCRA),
      multiple linear regression with genetic function approximation (GFA-MLR), and
      genetic partial least squares (G/PLS) were applied to identify the structural and
      physicochemical requirements for the CCR5 binding affinity. The generated
      equations were statistically validated using leave-one-out technique. The quality
      of equations obtained from stepwise regression, FA-MLR, FA-PLS, and PCRA is of
      acceptable statistical range (explained variance ranging from 71.9% to 80.4%,
      while predicted variance ranging from 67.4% to 77.0%). The GFA-derived models
      show high intercorrelation among predictor variables used in the equations while
      the G/PLS model shows lowest statistical quality among all types of models. The
      best models were also subjected to leave-25%-out crossvalidation.

PMID- 16806924
TI  - Synthesis and pharmacological study of novel pyrido-quinazolone analogues as anti
      fungal, antibacterial, and anticancer agents.
AB  - A versatile method for novel pyrido-quinazolones was described here and tested
      for anti-fungal, antibacterial, and anticancerous activities. These synthesized
      compounds were characterized on the basis of spectroscopic techniques and
      evaluated for specific radiopharmaceuticals. Preliminary radiolabeling results
      with (99m)Tc and biological evaluation studies showed promising results for
      further evaluation in vivo. The efficiency of labeling was more than 98% and
      complexes were stable for about 18 h at 25 degrees C in the presence of serum.

PMID- 16806925
TI  - Tri-substituted triazoles as potent non-nucleoside inhibitors of the HIV-1
      reverse transcriptase.
AB  - A new series of 1,2,4-triazoles was synthesized and tested against several NNRTI
      resistant HIV-1 isolates. Several of these compounds exhibited potent antiviral
      activities against efavirenz- and nevirapine-resistant viruses, containing K103N
      and/or Y181C mutations or Y188L mutation. Triazoles were first synthesized from
      commercially available substituted phenylthiosemicarbazides, then from
      isothiocyanates, and later by condensing the desired substituted anilines with
      thiosemicarbazones.

PMID- 16806926
TI  - Fluorogenic ester substrates to assess proteolytic activity.
AB  - The synthesis of a new type of fluorogenic ester substrates is described.
      Prepared from fluorescein in three steps with common commercially available
      precursors, they all generate bright green fluorescence upon proteolysis. Their
      particular structure allows the same substrate be used to report enzymatic
      activity of various proteases from serine and cysteine superfamilies. The
      substrate cleavage is sensitive to specific protease inhibitors providing a tool
      for inhibitor screening.

PMID- 16806927
TI  - Constitutive upregulations of titin-based signalling proteins in KY deficient
      muscles.
AB  - An increase in the expression of stretch/stress response elements in fast and
      slow muscles has been previously described in a transcriptional profiling of KY
      deficient muscles. Here, we have characterized the induction of this titin-based
      family of signalling proteins in ky/ky muscles at the protein level. Changes in
      expression of MLP, MARP2 and Xin have been related to the onset of dystrophic and
      adaptive changes that operate in ky/ky muscles. Our results indicate that
      induction of this set of genes is an early consequence of the interference caused
      by the absence of the KY protein. A search of muscle profiles of mouse models
      revealed such molecular hallmark only in muscles subjected to a single bout of
      eccentric contractions and specific titin mutants. Based on the role of this
      family as titin-based stress response molecules, it is suggested that titin
      structural/signalling instability is common to ky and titin mouse mutants and
      eccentric contractions.

PMID- 16806928
TI  - Mitochondrial myopathy with exercise intolerance and retinal dystrophy in a
      sporadic patient with a G583A mutation in the mt tRNA(phe) gene.
AB  - We describe a second patient with the 583G>A mutation in the tRNA(phe) gene of
      mitochondrial DNA (mtDNA). This 17-year-old girl had a mitochondrial myopathy
      with exercise intolerance and an asymptomatic retinopathy. Muscle investigations
      showed occasional ragged red fibers, 30% cytochrome c oxidase (COX)-negative
      fibers, and reduced activities of complex I+IV in the respiratory chain. The
      mutation was heteroplasmic (79%) in muscle but undetectable in other tissues.
      Analysis of single muscle fibers revealed a significantly higher level of mutated
      mtDNA in COX-negative fibers. Our study indicates that the 583G>A mutation is
      pathogenic and expands the clinical spectrum of this mutation.

PMID- 16806929
TI  - Decrement pattern in Lambert-Eaton myasthenic syndrome is different from
      myasthenia gravis.
AB  - The decrement pattern at low rates of repetitive nerve stimulation in myasthenia
      gravis (MG) is characterized by a decrease of compound muscle action potential
      size within the first 4-5 responses. With subsequent stimuli, compound muscle
      action potential size either increases or does not change. Following an
      observation that the pattern of decrement might be different in patients with
      Lambert-Eaton myasthenic syndrome (LEMS), we retrospectively studied traces from
      eight LEMS patients and 14 patients with seropositive generalized MG, calculating
      decrement percent from first to fourth and from first to ninth compound muscle
      action potential. In the LEMS patients, compound muscle action potential
      amplitude decreased progressively from first to ninth stimulus at 2, 3 or 5Hz in
      all traces but one. In contrast, MG patients demonstrated the expected
      improvement after the initial decrement in all traces except one. In the
      evaluation of patients suspected of having myasthenia gravis, the finding of
      progressive decrement pattern at low rates of repetitive nerve stimulation may
      alert the electromyographer to the possibility of Lambert-Eaton syndrome and
      prompt the performance of further electrodiagnostic tests.

PMID- 16806930
TI  - Clinical spectrum of CMT4C disease in patients homozygous for the p.Arg1109X
      mutation in SH3TC2.
AB  - We investigated the manifestations of CMT4C disease in a genetically homogeneous
      group of patients homozygous for the recently identified Gypsy founder mutation
      p.Arg1109X in SH3TC2. We observed a surprising degree of variation in age at
      onset, rate of progression, extent and severity of motor and sensory involvement,
      scoliosis, and cranial nerve involvement, suggesting that the phenotypic spectrum
      of CMT4C disease is much broader than the classical diagnostic criteria.
      Phenotype similarity in first degree relatives and increasing heterogeneity in
      more distantly related subjects point to the involvement of genetic modifiers,
      possibly variants in the genes encoding protein partners interacting with SH3TC2.

PMID- 16806931
TI  - Distinct phenotypic features and gender-specific disease manifestations in a
      Spanish family with desmin L370P mutation.
AB  - Desminopathies represent a subtype of myofibrillar myopathy caused by mutations
      in the DES gene, which cause myofibril disruption and intracellular inclusions
      containing desmin and other protein components. Desminopathy mainly involves
      skeletal and cardiac muscle, separately or together. Both autosomal dominant and
      autosomal recessive inheritance have been reported. Here, we describe the second
      family identified to date with an L370P desmin mutation. The disease in this
      family shows autosomal dominant inheritance with a particular phenotype, where
      males suffer from sudden death of cardiac origin while females exhibit a more
      benign myopathy of distal onset and slower progression. Because the only family
      previously identified with this mutation was limited to one studied patient, the
      present kindred represents the largest clinical investigation of the phenotype
      associated with the L370P mutation.

PMID- 16806932
TI  - Coronins: the return of the crown.
AB  - Coronins are highly conserved regulators of the actin cytoskeleton whose
      structure and biological function have remained mysterious until recently. They
      were originally identified in Dictyostelium, where they localize to actin-rich
      crown-like structures on the dorsal surface of cells. Coronins bind filamentous
      actin and the Arp2/3 complex and are involved in modulating actin dynamics.
      Unlike other known Arp2/3-binding proteins, coronins inhibit Arp2/3 nucleating
      activity. Genetic data from Dictyostelium, yeast and Drosophila indicate that
      coronins are important regulators of several actin-dependent physiological
      processes. Here, we review recent insights into mammalian coronin structure,
      function and regulation and identify key questions that remain unanswered in this
      field.

PMID- 16806933
TI  - Beyond comfort: oral hygiene as a critical nursing activity in the intensive care
      unit.
AB  - BACKGROUND: The role of oral hygiene in maintaining the health and well being of
      patients in the intensive care unit (ICU) is indisputable. This importance is not
      reflected in the body of research related to ICU practice. While a number of
      studies have examined oral hygiene practices in oncological patients there is
      significantly less attention devoted to these practices in the critically ill.
      AIM: This paper has two discrete yet interrelated aims. Firstly, in relation to
      current available evidence and based on a sound knowledge of oral physiology,
      identify barriers to effective oral hygiene and subsequent effectiveness of the
      most commonly used and recommended methods of providing oral hygiene in the
      critically ill population. Secondly, informed by the critical review, identify
      recommendations for practice and future intervention studies. FINDINGS: To date,
      there is no definitive evidence to determine the most appropriate method of oral
      hygiene including the use of beneficial mouth rinses. Barriers identified in this
      review to providing optimal hygiene include: (1) mechanical barriers and
      equipment issues, (2) perceptions of the importance of mouth care and empathy
      with patient discomfort by nurses, (3) altered patient sensory perception and
      discomfort and (4) difficulties in patient communication. In spite of these
      challenges opportunities for collaborative research and increasing expertise in
      nurse researchers creates a climate to derive solutions to these factors.
      CONCLUSIONS: It is clearly evident from this review of oral hygiene practices in
      intensive care that the need for ongoing research is of paramount importance. ICU
      nurses undeniably require rigorous research studies in order to inform their
      practice in the provision of oral hygiene for critically ill patients.

PMID- 16806934
TI  - Factors associated with pelvic retraction during gait in cerebral palsy.
AB  - Clinical and dynamic (gait-related) measures thought to be associated with pelvic
      retraction were investigated in patients with cerebral palsy. Gait laboratory
      data of 233 patients with cerebral palsy were studied retrospectively. Two groups
      were selected; those who demonstrated pelvic retraction during gait <-6.85
      degrees (mean - 2 standard deviations from normal (n=88) and those with >-4.83
      degrees (mean - 1 standard deviation from normal) (n=101). About 37.8% of the
      total population reviewed showed pelvic retraction of <-6.85 degrees . There was
      a higher prevalence of retraction among hemiplegics (46.3%) compared to diplegics
      (30.4%). Differences were also found between hemiplegic and diplegic subjects in
      terms of factors associated with pelvic retraction. Clinical and dynamic
      tightness of the gastro-soleus were the most significant features associated with
      pelvic retraction among hemiplegic subjects. Clinical and dynamic flexion and
      internal rotation of the hip were the most significant features associated with
      retraction in the diplegic population. This study suggests that pelvic retraction
      is multifactorial in origin and secondary to both static clinical measures as
      well as dynamic features during gait.

PMID- 16806935
TI  - Postural responses to specific types of working memory tasks.
AB  - Standing participants performed working memory tasks that varied along three
      dimensions: (1) type of information presented (verbal or visual); (2) the primary
      cognitive process engaged (encoding or rehearsal); and (3) interference that
      targeted the working memory components (phonological loop and visual sketchpad)
      believed primarily active during rehearsal. Postural sway variability decreased
      during rehearsal and increased during encoding. The effects during encoding, but
      not during rehearsal, differed for verbal versus visual material. Changes in
      cognitive activity were also associated with changes in the temporal patterns of
      postural sway. The results suggest postural control is sensitive to the type of
      cognitive task performed.

PMID- 16806936
TI  - Tools to study molecular mechanisms of Aspergillus pathogenicity.
AB  - The unique nature of Aspergillus fungi represents a challenge for scrutinizing
      the attributes that render these saprophytic microorganisms pathogenic or
      allergenic under certain environmental circumstances. Recent publication of the
      genomic sequence from an isolate of the major pathogen Aspergillus fumigatus
      denotes enormous progress in aiming at cellular features and gene products that
      contribute to its pathogenicity. Latest developments to study virulence-related
      characteristics comprise profiling techniques, conditional gene inactivation and
      precise manipulation of the genome by means of gene targeting. Advances in
      assessing the virulence potential of particular mutant strains in alternative
      test systems complement these approaches.

PMID- 16806937
TI  - Medial double-plating for fracture dislocations involving the proximal tibia.
AB  - Fracture dislocations of the knee involving the proximal tibia are difficult to
      treat because of the operative approach that maybe required and the instability
      of the construct. This paper evaluates the use of a two-incision approach with a
      medial double-plating technique. The clinical results of a case series of 42
      patients collected prospectively are presented. At final follow-up 37 out of 42
      (88%) had satisfactory reduction of the articular surface and 41 (98%) had
      satisfactory alignment. At one year postoperation there was no loss in reduction
      or alignment. The mean HSS score was 90.9 (s.d. 3.35, range 83 to 97). There were
      no superficial or deep infections, however four cases (10%) had a sanguinous
      effusion for more than one week postoperatively. It was concluded that the medial
      double-plating operation is an effective way of managing fracture dislocations
      involving the proximal tibia.

PMID- 16806938
TI  - The meniscal flounce: a valuable arthroscopic sign.
AB  - PURPOSE: The purpose of this study was to characterise the incidence and
      significance of the meniscal flounce. TYPE OF STUDY: Prospective Cohort Study.
      METHOD: A prospective study of 1088 consecutive knee arthroscopies. RESULTS:
      Intact menisci tended to have a flounce of characteristic size and position. The
      presence of this 'normal' flounce was closely correlated with an intact meniscus
      (p<0.0001). For the medial meniscus with a small flounce in zone 3 the
      sensitivity, specificity, and positive predictive value (PPV) for an intact
      medial meniscus were 68.5%; 92.9%; and 92.1% respectively. Conversely the
      presence of meniscal pathology correlated closely with either an absent or
      abnormal flounce (p<0.0001). The absence of a medial flounce had sensitivity,
      specificity, and PPV for a meniscal tear of 82.8%; 84.9%; and 81.9% respectively.
      CONCLUSIONS: The findings of this study are useful for arthroscopists especially
      when there is difficulty visualising all of the posterior half of the meniscus.
      In this situation the presence of a normal flounce is likely to signify an intact
      meniscus. However the presence of an abnormal or absent flounce may be the sign
      of an occult meniscal tear requiring better exposure.

PMID- 16806939
TI  - Bilateral dislocation of the knee with rupture of both patellar tendons. A case
      report.
AB  - Knee dislocations are rare injuries caused by violent trauma. Damage to soft
      tissues and ligament lesions almost always accompany the injury. Vascular
      compromise further complicates the situation. We report a case of bilateral
      posterior knee dislocation with traumatic rupture of both patellar tendons.
      Treatment consisted of external fixation of both knees. Vascular compromise
      resolved with reduction and traction pins were placed on both patellae which were
      connected to the external fixators on following days. Primary repair of patellar
      tendon was undertaken after gradual distal repositioning of patella. The result
      is successful with full range of motion. Rupture of patellar tendon should be
      considered with posterior dislocation of the knee. External fixators provide
      quick stabilization in case of vascular compromise and can be modified to provide
      a traction system for distal repositioning of patella which allows primary repair
      of the patellar tendon.

PMID- 16806940
TI  - Pyrexia following total knee replacement.
AB  - This study aims to determine the incidence and factors associated with pyrexia
      following total knee replacement (TKR). We performed a retrospective analysis of
      the temperature charts and histories of patients who underwent 170 TKRs. There
      was a statistically significant increase in mean temperature from pre-operation
      to post-operation, and this increase remained significant through to 5 days post
      surgery (p<0.0001). Sixty-two (36.5%) patients were pyrexial (>or=38 degrees C)
      at some point. Fourteen patients developed a clinical infection, but only four of
      these were pyrexial. There was no association between pyrexia and infection,
      allogenic blood transfusion, haemoglobin loss, use of urinary catheter,
      rheumatoid arthritis, anaesthetic type, and previous pyrexia following TKR.
      Pyrexia as a diagnostic test for the development of infection had a sensitivity
      of 0.286 (95% CI=0.084-0.581), specificity of 0.628 (95% CI=0.548-0.704) and
      positive predictive value of 0.065 (95% CI=0.018-0.157). Pyrexia in the first 5
      days following TKR is usually a normal physiological response and should not
      cause undue concern about the presence of infection.

PMID- 16806941
TI  - Medium-term results of the Scorpio total knee replacement.
AB  - We performed a medium-term clinical and radiological analysis of 160 patients
      (173 knees) who underwent Scorpio total knee arthroplasty between August 1997 and
      September 2000. Seventeen patients (19 knees) were lost to follow-up and 29
      patients (29 knees) died before completing a minimum 5 year follow-up. The mean
      age of the patients at the time of the operation was 73.5 years and the mean
      duration of follow-up was 5 years and ten months. At the time of latest follow
      up, the mean knee score was 92 and the mean functional score was 65. Overall, 104
      knees were rated as excellent, 12 knees as good, 8 knees as fair, and one knee as
      poor. Thin, incomplete, non-progressive radiolucent lines were noted around eight
      tibial components and one femoral component. Massive osteolysis in the tibia was
      observed in one case. Only one patient needed revision of the prosthesis. Our
      findings suggest that the prosthesis design with a single flexion extension
      radius is associated with a good medium-term outcome.

PMID- 16806942
TI  - A systematic literature review to investigate if we identify those patients who
      can cope with anterior cruciate ligament deficiency.
AB  - Rupture of the anterior cruciate ligament (ACL) results in increased tibiofemoral
      laxity in the knee, thereby ultimately resulting in knee instability and
      dysfunction. However, ACL rupture does not automatically infer functional
      impairment and instability as confirmed by the ACL deficient (ACLD) coper, who
      can resume pre-morbid activity levels. Alternatively, an authentic ACLD non-coper
      is unable to return to pre-injury levels of activity due to repeated incidents of
      giving-way. Little is known as to the contributory factors, which allows copers
      dynamic stability and render non-copers functionally impaired. This systematic
      literature review aims to examine the evidence presented by relevant trials in
      order to identify measurement tools, which could differentiate ACLD copers and
      non-copers. A literature search found nine trials; four adhered to the inclusion
      criteria of this review. Consensus was achieved within the studies that laxity
      measurements and IKDC ratings are incapable of distinguishing the functional
      status of the ACLD patient. Alternatively, Lysholm, KOS-Sport, KOS-ADL and Global
      Knee Function Rating Scores were regarded as capable of discriminating between
      ACLD copers and non-copers. Disagreement existed as to the efficacy of the
      Quadriceps Index and the single leg hop in categorising the ACLD patient
      according to function level. It was concluded that no single measurement tool is
      sufficient in determining the functional status of the ACLD individual.
      Consequently, a collaboration of tests is recommended, specifically incorporating
      the KOS-Sport, Global Knee Function Rating, hop tests and Quadriceps Index.

PMID- 16806943
TI  - Synthesis and cytotoxic activities of beta-carboline amino acid ester conjugates.
AB  - Beta-carboline represents a class of compounds with potent anti-tumor activity by
      intercalating with DNA. To further enhance the cytotoxic potency and
      bioavailability of beta-carboline, a series of novel beta-carboline amino acid
      ester conjugates were designed and synthesized, and the cytotoxic activities of
      these compounds were tested using a panel of human tumor cell lines. In addition,
      the membrane permeability of these compounds was evaluated in vitro using a Caco
      2 cell monolayer model. The beta-carboline amino acid ester conjugates
      demonstrated improved cytotoxic activity compared to the parental beta
      carbolines. In particular, the Lys/Arg conjugates were the most potent analogs
      with an IC(50) value of 4 and 1 microM against human cervical carcinoma cells.
      The low interaction energy of Arg conjugate based on molecular modeling may
      contribute to its enhanced cytotoxicity. Taken together, this study provided new
      insights into structure-activity relationships in the beta-carboline amino acid
      ester conjugates and identified the beta-carboline Lys/Arg conjugates as
      promising lead compounds for further in vivo biological and molecular evaluation.

PMID- 16806944
TI  - Synthesis and in vitro antitumor evaluation of some indeno[1,2-c]pyrazol(in)es
      substituted with sulfonamide, sulfonylurea(-thiourea) pharmacophores, and some
      derived thiazole ring systems.
AB  - The synthesis of a series of 3-(4-chlorophenyl)-[1,2-c]pyrazol(in)es substituted
      with benzenesulfonamide, N1,N3-disubstituted sulfonylurea, sulfonylthiourea
      pharmacophores, and some derived thiazolidinone and thiazoline ring systems is
      described. All the newly synthesized target compounds were subjected to the NCI
      in vitro disease-oriented antitumor screening to be evaluated for their antitumor
      activity. Eight compounds namely; 2-4, 7, 8, 10, 13, and 16; showed promising
      broad spectrum antitumor activity against most of the tested subpanel tumor cell
      lines (GI50 < 100 microM). Compound 3, 4-(3-(4-chlorophenyl)-4H-indeno[1,2
      c]pyrazol- 2-yl)-benzenesulfonamide; although it did not show the highest growth
      inhibitory value (GI50 (MG-MID) 13.2 microM), it proved to be the most active
      analog in this study with the highest cytostatic and cytotoxic potentials (TGI
      and LC50 (MG-MID) concentrations of 33.1 and 66.1 microM, respectively). In
      general, the oxidized pyrazoles displayed better antitumor activity than their
      parent pyrazoline analogs, whereas the benzenesulfonamides and the N1, N3
      disubstituted sulfonylureas showed significant better antitumor spectrum than the
      sulfonylthioureido and the derived thiazole analogs.

PMID- 16806945
TI  - Design, synthesis, and biological evaluation of 1,2,3-trisubstituted-1,4
      dihydrobenzo[g]quinoxaline-5,10-diones and related compounds as antifungal and
      antibacterial agents.
AB  - A series of (S)-N-(3-chloro-1,4-naphthoquinon-2-yl)-alpha-amino acid ethyl esters
      3 and 1,2,3-trisubstituted-1,4-dihydrobenzo[g]quinoxaline-5,10-diones 6-23 were
      synthesized and evaluated for antifungal and antibacterial activities. The
      structure-activity relationship of these compounds was studied and the results
      show that the compounds 3a and 3b exhibited in vitro antifungal activity against
      Candida albicans, Cryptococcus neoformans, and Sporothrix schenckii whereas
      compounds 12 and 22 showed in vitro antibacterial activity against Klebsiella
      pneumoniae and Escherichia coli.

PMID- 16806946
TI  - New progesterone receptor antagonists: phosphorus-containing 11beta-aryl
      substituted steroids.
AB  - A new series of phosphorus-containing 11beta-aryl-substituted steroids have been
      synthesized in an eight-step sequence involving a palladium-catalyzed coupling
      reaction to introduce a phosphorus group onto the aromatic ring. The compounds
      were evaluated for progesterone receptor (PR) antagonist activity in a T47D cell
      based assay and for glucocorticoid receptor (GR) antagonist activity in an A549
      cell-based assay. The structure-activity relationships of these compounds are
      discussed. Selected compounds were tested in vivo in a rat complement C3 assay.

PMID- 16806947
TI  - The synthesis of L-carvone and limonene derivatives with increased
      antiproliferative effect and activation of ERK pathway in prostate cancer cells.
AB  - Thirty-one novel derivatives of carvone, carveol, and limonene were designed and
      synthesized using L-carvone as a starting material via chlorination, nucleophilic
      substitution, and reduction. The structures of these derivatives were
      characterized by MS and 1H NMR. The antiproliferative effect was evaluated in
      human prostate cancer LNCaP cells. L-carvone, L-carveol, and L-limonene were weak
      cell growth inhibitors and introduction of 4-(2-methoxyphenyl)piperazine to
      carvone, carveol or limonene significantly increased their antiproliferative
      effect. The antiproliferative effect was correlated with ERK activation and
      p21(waf1) induction.

PMID- 16806948
TI  - Synthesis and beta-lactamase reactivity of alpha-substituted phenaceturates.
AB  - Beta-lactams with 6alpha (penicillins) or 7alpha (cephalosporins) substituents
      are often beta-lactamase inhibitors. This paper assesses the effect of such
      substituents on acyclic beta-lactamase substrates. Thus, a series of m
      carboxyphenyl phenaceturates, substituted at the glycyl alpha-carbon by -OMe, 
      CH(2)OH, -CO(2)(-), and -CH(2)NH(3)(+), have been prepared, and tested for their
      reactivity against serine beta-lactamases. The latter two are novel substituents
      in beta-lactamase substrates. The methoxy and hydroxymethyl compounds were found
      to be poor to moderately good substrates, depending on the enzyme. The
      aminomethyl compound gave rise to a transiently stable (t(1/2)=4.6s) complex on
      its reaction with a class C beta-lactamase. The reactivity of the compounds
      against three low molecular weight DD-peptidases was also tested. Again, the
      methoxy and hydroxymethyl compounds proved to be quite good substrates with no
      sign of inhibitory complexes. The DD-peptidases reacted with one enantiomer (the
      compounds were prepared as racemates), presumably the D compound. The class C
      beta-lactamase reacted with both D and L enantiomers although it preferred the
      latter. The structural bases of these stereo-preferences were explored by
      reference to the crystal structure of the enzyme by molecular modeling studies.
      The aminomethyl compound was unreactive with the DD-peptidases, whereas the
      carboxy compound did not react with any of the above-mentioned enzymes. The
      inhibitory effects of the -OMe and -CH(2)OH substituents in beta-lactams
      apparently require a combination of the substituent and the pendant leaving group
      of the beta-lactam at the acyl-enzyme stage.

PMID- 16806949
TI  - Captive solvent [11C]acetate synthesis in GMP conditions.
AB  - Reliable procedure for the production of 1-[(11)C]acetate in GMP conditions was
      developed based on a combination of the captive-solvent Grignard reaction
      conducted in the sterile catheter followed by the convenient solid-phase
      extraction purification on a series of ion-exchange cartridges. The described
      procedure proved to be reliable in more than 30 patient productions. The process
      provides stable radiochemical yields (65% EOB) of sodium acetate (1-[(11)C]) of
      the Ph.Eur. quality (radiochemical purity better than 95%) in a short time (5
      min).

PMID- 16806950
TI  - A theoretical model for the production of Ac-225 for cancer therapy by photon
      induced transmutation of Ra-226.
AB  - Radium needles that were once implanted into tumours as a cancer treatment are
      now obsolete and constitute a radioactive waste problem, as their half-life is
      1600 years. We are investigating the reduction of radium by transmutation on a
      small scale by bombarding Ra-226 with high-energy photons from a medical linear
      accelerator (linac) to produce Ra-225, which subsequently decays to Ac-225, which
      can be used as a generator to produce Bi-213 for use in 'targeted alpha therapy'
      for cancer. This paper examines the possibility of producing Ac-225 with a linac
      using an accurate theoretical model in which the bremsstrahlung photon spectrum
      at 18 MV linac electron energy is convoluted with the corresponding photonuclear
      cross sections of Ra-226. The total integrated yield can then be obtained and is
      compared with a computer simulation. This study shows that at 18 MV, the
      photonuclear reaction on Ra-226 can produce low activities of Ac-225 with a
      linac. However, a high power linac with high current, pulse length and frequency
      is needed to produce practical amounts of Ac-225 and a useful reduction of Ra
      226.

PMID- 16806951
TI  - Neuroprotection by two polyphenols following excitotoxicity and experimental
      ischemia.
AB  - Brain ischemia induces neuronal loss which is caused in part by excitotoxicity
      and free radical formation. Here, we report that mangiferin and morin, two
      antioxidant polyphenols, are neuroprotective in both in vitro and in vivo models
      of ischemia. Cell death caused by glutamate in neuronal cultures was decreased in
      the presence of submicromolar concentrations of mangiferin or morin which in turn
      attenuated receptor-mediated calcium influx, oxidative stress as well as
      apoptosis. In addition, both antioxidants diminished the generation of free
      radicals and neuronal loss in the hippocampal CA1 region due to transient
      forebrain ischemia in rats when administered after the insult. Importantly,
      neuroprotection by these antioxidants was functionally relevant since treated
      ischemic rats performed significantly better in three hippocampal-dependent
      behavioral tests. Together, these results indicate that mangiferin and morin have
      potent neuroprotectant activity which may be of therapeutic value for the
      treatment of acute neuronal damage and disability.

PMID- 16806952
TI  - Ventral tegmental area dopamine neurons are resistant to human mutant alpha
      synuclein overexpression.
AB  - Parkinson's disease (PD) is characterized by the formation of intracytoplasmic
      inclusions, which contain alpha-synuclein (alpha-syn) protein. While most
      profound neurodegeneration is seen in the dopamine (DA) synthesizing neurons
      located in the ventral midbrain, it is unclear why some DA cell groups are more
      susceptible than others. In the midbrain, the degeneration of the substantia
      nigra (SN) DA neurons is severe, whereas the involvement of the ventral tegmental
      area (VTA) neurons is relatively spared. In the present study, we overexpressed
      human A53T alpha-syn in the VTA neurons and found that A53T toxicity did not
      affect their survival. There was, however, a mild functional impairment seen as
      altered open field locomotor activity. Overexpression of A53T in the SN, on the
      other hand, led to profound cell loss. These results suggest that the selective
      susceptibility of nigral DA neurons is at least in part associated with factor(s)
      involved in handling of alpha-syn that is not shared by the VTA neurons.
      Secondly, these results highlight the fact that impaired but surviving neurons
      can have a substantial impact on DA-dependent behavior and should therefore be
      considered as a critical part of animal models where novel therapeutic
      interventions are tested.

PMID- 16806953
TI  - Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal
      neurogenesis with attenuation of spontaneous recurrent seizures following
      pilocarpine-induced status epilepticus.
AB  - Recent evidences suggest key roles of abnormal neurogenesis and astrogliosis in
      the pathogenesis of epilepsy. Alterations in the microenvironment of the stem
      cell, such as microglial activation and cyclooxygenase-2 induction may cause
      ectopic neurogenesis or astrogliosis. Here, we examined if inflammatory blockade
      with celecoxib, a selective cyclooxygenase-2 inhibitor, could modulate the
      altered microenvironment in the epileptic rat brain. Celecoxib attenuated the
      likelihood of developing spontaneous recurrent seizures after pilocarpine-induced
      prolonged seizure. During the latent period, celecoxib prevented neuronal death
      and microglia activation in the hilus and CA1 and inhibited the generation of
      ectopic granule cells in the hilus and new glia in CA1. The direct inhibition of
      precursor cells by celecoxib was further demonstrated in human neural stem cells
      culture. These findings raise the evidence of COX-2 induction to act importantly
      on epileptogenesis and suggest a potential therapeutic role for COX-2 inhibitors
      in chronic epilepsy.

PMID- 16806954
TI  - Biosynthesis of flavan 3-ols by leucoanthocyanidin 4-reductases and anthocyanidin
      reductases in leaves of grape (Vitis vinifera L.), apple (Malus x domestica
      Borkh.) and other crops.
AB  - Catechin and epicatechin biosyntheses were studied of grape (Vitis vinifera L.),
      apple (Malus x domestica Borkh.) and other crop leaves, since these monomers and
      the derived proanthocyanidins are important disease resistance factors. Grape and
      apple leucoanthocyanidin 4-reductase (LAR; EC 1.17.1.3) enzymes were
      characterized on basis of plant and recombinant enzymes. In case of grape, two
      LAR cDNAs were cloned by assembling available EST sequences. Grape and apple leaf
      anthocyanidin reductase (ANR; EC 1.3.1.77) cDNAs were also obtained and the
      respective plant and recombinant enzymes were characterized. Despite general low
      substrate specificity, within the respective flavonoid biosyntheses of grape and
      apple leaves, both enzyme types deliver differently hydroxylated catechins and
      epicatechins, due to substrate availability in vivo. Furthermore, for LAR enzymes
      conversion of 3-deoxyleucocyanidin was shown. Beside relevance for plant
      protection, this restricts the number of possible reaction mechanisms of LAR. ANR
      enzyme activity was demonstrated for a number of other crop plants and its
      correlation with (-)-epicatechin and obvious competition with UDP
      glycosyl:flavonoid-3-O-glycosyltransferases was considered.

PMID- 16806955
TI  - Nickel elicits a fast antioxidant response in Coffea arabica cells.
AB  - The antioxidant responses of coffee (Coffea arabica L.) cell suspension cultures
      to nickel (Ni) were investigated. Ni was very rapidly accumulated in the cells
      and the accumulation could be directly correlated with the increase of NiCl(2)
      concentration in the medium. At 0.05 mM NiCl(2) growth was stimulated, but at 0.5
      mM NiCl(2), the growth rate was reduced. An indication of alterations in the
      presence of reactive oxygen species was detected by an increase in lipid
      peroxidation at 0.5 mM NiCl(2). Catalase (CAT; EC 1.11.1.6), glutathione
      reductase (GR; EC 1.6.4.2), ascorbate peroxidase (APX; EC 1.11.1.11), guaiacol
      peroxidase (GOPX; EC 1.11.1.7) and superoxide dismutase (SOD; EC 1.15.1.1)
      activities were increased, particularly at earlier NiCl(2) exposure times and the
      activities were higher at 0.5 mM NiCl(2) for most of exposure times tested. Non
      denaturing PAGE revealed one CAT isoenzyme, nine SOD isoenzymes and four GR
      isoenzymes. The SOD isoenzymes were differentially affected by NiCl(2) treatment
      and one GR isoenzyme was increased by NiCl(2). NiCl(2) at 0.05 mM did not induce
      lipid peroxidation and the main response appeared to be via the induction of SOD,
      CAT, GOPX and APX activities for the removal of the reactive oxygen species and
      through the induction of GR to ensure the availability of reduced glutathione.

PMID- 16806956
TI  - Protein phosphorylation and membrane association of sucrose synthase in
      developing tomato fruit.
AB  - Calcium-dependent protein kinase (CDPK) activities were detected both in the
      soluble and the membrane fraction of various tomato (Lycopersicon esculentum
      Mill.) organs, using a synthetic peptide mimicking the serine 11 phosphorylation
      site of a tomato sucrose synthase (SS, EC 2.4.1.13) isoform as substrate. The
      levels of membrane and soluble Ser-CDPK activities were differentially regulated
      during fruit development. The membrane Ser-CDPK activity was maximal in young
      fruit but decreased as the fruit developed, suggesting a specific role during
      fruit growth. Using an in gel assay with purified tomato SS as substrate, we
      showed that partially purified soluble and membrane Ser-CDPK preparations both
      contained a SS-kinase polypeptide of 55 kDa. The membrane and soluble Ser-CDPK
      activities were largely inactivated in the absence of calcium or when MgCl(2) was
      replaced by MnCl(2). Both soluble and membrane Ser-CDPK activities were very
      sensitive to staurosporine. Using Fe(III)-immobilized metal chromatography to
      determine the apparent phosphorylation status of the enzyme in vivo, we showed
      that soluble SS was largely dephosphorylated in fruits fed EGTA or staurosporine,
      compared to fruits fed water or sucrose. Moreover, the level of SS increased by
      about two-fold in the membrane fraction of fruits fed the Ser-CDPK inhibitors,
      compared to the control. The level of SS protein in the membrane and soluble
      fractions of tomato fruit was developmentally regulated, the membrane form being
      specifically detected in actively growing fruits. Together, our results suggest
      that a mechanism involving protein phosphorylation/dephosphorylation and/or
      calcium would in part control the association of SS isoforms with membranes in
      developing tomato fruit.

PMID- 16806957
TI  - Aster tripolium L. and Sesuvium portulacastrum L.: two halophytes, two strategies
      to survive in saline habitats.
AB  - Aster tripolium L. (Dollart, Germany) and Sesuvium portulacastrum L. (Dakhla,
      Morocco) are potential halophytic vegetables, fodder plants, and ornamentals for
      re-vegetating saline land. To compare their strategies involved in salt tolerance
      both plants were grown with 0%, 1.5%, and 3% (Aster) or 0%, 2.5%, and 5%
      (Sesuvium) NaCl in the watering solution. The growth rate was reduced in both
      species with increasing NaCl concentrations. The quotient of Na(+)/K(+) indicates
      that Aster accumulates more K(+) in comparison to Na(+) while the reverse is true
      for Sesuvium. Osmolality of the leaf sap increased with increasing NaCl
      concentration in both Aster and Sesuvium. Transpiration rate was severely reduced
      in both Aster (3%) and Sesuvium (5%) plants after 10 d of NaCl watering. The
      CO(2) assimilation rate decreased in Aster (3%) and Sesuvium (5%) NaCl-treated
      plants from day 5 to day 10. The most important results from chlorophyll
      fluorescence measurements were derived from the non-photochemical quenching
      analysis (NPQ). First, both plants had linearly increasing levels of NPQ with
      increasing NaCl concentrations. Second, Sesuvium had almost half the NPQ value
      when compared to Aster under increased soil salinity. In Aster P-ATPase
      activities were decreased in plants treated with 3% NaCl after three days of
      treatment, F-ATPase activities increased with increasing NaCl concentrations and
      no clear changes were measured in V-ATPase activities. In Sesuvium any changes
      could be observed in the three ATPase activities determined. To conclude, Aster
      and Sesuvium use different strategies in adaptation to soil salinity.

PMID- 16806958
TI  - Effects of ABA, auxin, and gibberellin on the expression of genes for vacuolar H+
      -inorganic pyrophosphatase, H+ -ATPase subunit A, and Na+/H+ antiporter in
      barley.
AB  - We analyzed the effects of ABA, auxin, and gibberellin on the expression of two
      genes (HVP1 and HVP10) for vacuolar H(+)-inorganic pyrophosphatase (EC 3.6.1.1)
      and one (HvVHA-A) for the catalytic subunit (subunit A) of vacuolar H(+)-ATPase
      (EC 3.6.1.3) by quantification of the transcript levels, to identify the hormones
      responsible for regulating the expression of these genes in barley (Hordeum
      vulgare L.) in response to environmental changes such as salt stress. ABA
      markedly induced the expression of HVP1 and slightly increased the expression of
      HVP10 and HvVHA-A. In contrast, 2,4-D only increased the expression of HVP1, and
      GA(3) had no significant effects on any gene. The maximum level of HVP1
      transcripts in response to these hormones was also much higher than the levels of
      HVP10 and HvVHA-A transcripts. In addition, we also analyzed the expression of
      one gene (HvNHX1) for vacuolar Na(+)/H(+) antiporter, and HvNHX1 expression
      changed in a pattern similar to that of the HVP1 expression. Furthermore,
      treatment with ABA and 2,4-D increased Na(+)/H(+) antiport activity and proton
      translocating activities by H(+)-PPase and H(+)-ATPase in tonoplast vesicles, and
      treatment with ABA also increased the amount of V-PPase protein of tonoplast
      vesicles. These results suggest that the hormones ABA and 2,4-D regulate the
      expression of the H(+)-pump and Na(+)/H(+) antiporter genes and are thus
      important effectors that regulate the expression of HVP1and HvNHX1.

PMID- 16806959
TI  - Role of defense/stress-related marker genes, proteins and secondary metabolites
      in defining rice self-defense mechanisms.
AB  - Rice, a first cereal crop whose draft genome sequence from two subspecies
      (japonica-type cv. Nipponbare and indica-type 93-11) was available in 2002, along
      with its almost complete genome sequence in 2005, has drawn the attention of
      researchers worldwide because of its immense impact on human existence. One of
      the most critical research areas in rice is to discern the self-defense
      mechanism(s), an innate property of all living organisms. The last few decades
      have seen scattered research into rice responses to diverse environmental stimuli
      and stress factors. Our understanding on rice self-defense mechanism has
      increased considerably with accelerated research during recent years mainly due
      to identification and characterization of several defense/stress-related
      components, genes, proteins and secondary metabolites. As these identified
      components have been used to study the defense/stress pathways, their compilation
      in this review will undoubtedly help rice (and others) researchers to effectively
      use them as a potential marker for better understanding, and ultimately, in
      defining rice (and plant) self-defense response pathways.

PMID- 16806960
TI  - The development of platinum compounds and their possible combination.
AB  - Cisplatin plays a central role in cancer chemotherapy in spite of its toxicity.
      To circumvent this toxicity and to enhance its therapeutic index a lot of
      preclinical and clinical studies have been conducted and several thousand
      analogues have been synthesized. Much more analysis remains to be done, but
      nowadays, the absence of any definitive, biologically interpretable molecular
      predictor of activity is consistent with the idea that platinum compounds have
      multiple intracellular targets and that cells can have multiple mechanisms of
      resistance. This review analyses a part of these platinum compounds analyzed to
      date, their mechanism of action, resistance and the future trends in this sector.

PMID- 16806961
TI  - Geriatric assessment for oncologists: rationale and future directions.
AB  - Sixty percent of all cancer occurrences and seventy percent of cancer mortalities
      occur in people over the age of 65. As the population ages, there is an emerging
      need to develop a means for oncologists to characterize the "functional age" of
      older patients with cancer in order to tailor treatment decisions and stratify
      outcomes based on factors other than chronological age and to develop
      interventions to optimize cancer treatment. In this paper, we discuss the
      formulation of a geriatric assessment for older patients with cancer. The
      measures included in this assessment were chosen based on their validity,
      reliability, brevity, adaptability for self-administration, and ability to
      prognosticate risk for morbidity or mortality in an older patient. The proposed
      geriatric assessment covers the essential domains of assessment predictive of
      survival in the geriatric population, is primarily self-administered, and limited
      personnel time is required. Our eventual goal is to determine if this geriatric
      assessment measure can identify factors independent of age that predict cancer
      treatment morbidity and mortality and result in rationale interventions to
      optimize oncologic care.

PMID- 16806962
TI  - Oxaliplatin-related neurotoxicity: how and why?
AB  - In early clinical trials, oxaliplatin has demonstrated significant activity
      against colorectal cancer in combination with 5-fluorouracil (5-FU) and folinic
      acid (FA), both in metastatic as in radically resected disease. The drug differs
      from the other two most important platinum compounds (cisplatin and carboplatin)
      for the absence of nephrotoxicity or for the reduced drug-induced ototoxicity.
      During its administration, two different types of neurological symptoms can be
      experienced: the first one occurs during or immediately after the end of the
      infusion and it appears as a transient peripheral sensory neuropathy manifesting
      as paresthesias and dysesthesia in the extremities sometimes accompanied by
      muscular contractions of the extremities or the jaw (triggered or enhanced by
      exposure to cold). The second one occurs after long-term administration of
      oxaliplatin presenting with deep sensory loss, sensory ataxia and functional
      impairment (similar to those observed with cisplatin). This type of neurotoxicity
      is usually late-onset and correlated with the cumulative-dose of oxaliplatin. The
      aim of this review is to analyse the mechanism underlying induction of
      neurotoxicity and the possible treatments to prevent and to treat it.

PMID- 16806963
TI  - Cetuximab in advanced non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) remains a major problem in the western
      civilization and developing countries. Since most patients with NSCLC have
      advanced disease at diagnosis, to date, chemotherapy, with third-generation
      platinum-based doublets, represents the standard of care. Advances in the
      knowledge of tumour biology and mechanisms of oncogenesis has granted the
      singling out of several molecular targets for NSCLC treatment. Epidermal growth
      factor receptor (EGFR), a member of ErbB family, is one of the most studied
      target. Cetuximab is a chimeric (human-murine) monoclonal antibody directed
      against the extracellular domain of the EGFR that blocks ligand (TGF-alpha, EGF)
      access to the receptor. In the present paper we discuss about the activity,
      tolerability and efficacy of cetuximab, the EGFR monoclonal blocking antibody
      with the largest amount of clinical data being available on the treatment of
      advanced NSCLC.

PMID- 16806964
TI  - Chaperoning steroid hormone action.
AB  - Those that efface themselves in the action tend to be forgotten. But molecular
      chaperones are always there, often serving as equal partners. Because of their
      intrinsic functional frailty, a large number of signaling molecules have come to
      depend on molecular chaperones, notably the Hsp90 chaperone machine. This applies
      to the subset of nuclear receptors that converts steroid hormone signals to
      transcriptional outputs. Steroid receptors appear to rely on the Hsp90 machine
      for folding, regulation of the allosteric switch and recycling. This review
      discusses the complexities of the chaperone machinery and the diversity of
      regulatory options afforded by this assistance for hormone action.

PMID- 16806965
TI  - Closing the link in short-loop prolactin feedback.
AB  - Short-loop negative feedback actions of prolactin in hypothalamus have been
      recognized for some time. Two recent papers demonstrate the multiple sites of
      this feedback action and the signaling mechanisms involved.

PMID- 16806966
TI  - Cancer stem cells: differentiation block or developmental back-tracking?

PMID- 16806967
TI  - The truncated 23-230 form of the prion protein localizes to the nuclei of
      inducible cell lines independently of its nuclear localization signals and is not
      cytotoxic.
AB  - The mechanisms of prion-induced neurological dysfunction observed in prion
      diseases are poorly understood. Transgenic mice expressing a truncated form of
      the prion protein (23-230 PrP) acquire cerebellar degeneration (Ma and Lindquist,
      Science, 2002). To decipher the mechanisms of neurodegeneration induced by 23-230
      PrP, we established inducible cell lines expressing this truncated form of PrP.
      We found that 23-230 PrP, expected to be cytosolic, accumulated mostly in the
      nucleus of the cells and was not cytotoxic. Nuclear localization of this mutant
      form of PrP is independent of its predicted nuclear localization signals. In
      contrast to what we previously described for PrPSc, nuclear accumulation of 23
      230 PrP does not require a functional microtubule network. We observed that 23
      230 PrP interacts with chromatin in vivo, as already described for recombinant
      PrP and for PrPSc. Our data demonstrate that the 23-230 PrP model does not
      reflect the situation of a cytosolic PrP but could represent a very useful tool
      to understand the consequences of the accumulation of the prion protein in the
      nucleus.

PMID- 16806968
TI  - Cracking the genome's second code: enhancer detection by combined phylogenetic
      footprinting and transgenic fish and frog embryos.
AB  - Genes involved in vertebrate development are unusually enriched for highly
      conserved non-coding sequence elements. These regions are readily detected in
      silico, by genome-wide sequence comparisons between different vertebrates, from
      mammals to fish (phylogenetic footprinting). It follows that sequence
      conservation must be the result of positive selection for an essential
      physiological role. An obvious possibility is that these conserved sequences
      possess regulatory or structural functions important for gene expression and,
      thus, an in vivo assay becomes necessary. We have developed a rapid testing
      system using zebrafish and Xenopus laevis embryos that allows us to assign
      transcriptional regulatory functions to conserved non-coding sequence elements.
      The sequences are cloned into a vector containing a minimal promoter and the GFP
      reporter, and are assayed for their putative cis-regulatory activity in zebrafish
      or Xenopus transgenic experiments. Vectors used include plasmid DNA and the Tol2
      transposon system in fish and X. laevis. We have followed this logic to detect
      and analyze conserved elements in an intergenic region present in the Iroquois
      (Irx) gene clusters of zebrafish, Xenopus tropicalis, Fugu rubripes and mouse. We
      have assayed approximately 50 of these conserved elements and shown that the
      majority behave as modular positive regulatory elements (enhancers) that
      contribute to specific temporal and spatial domains that are part of the
      endogenous gene expression pattern. Moreover, comparison of the activity of
      cognate Irx enhancers from different organisms demonstrates that conservation of
      sequence is accompanied by in vivo functional conservation across species.
      Finally, for some of the most conserved elements, we have been able to identify a
      critical core sequence, essential for correct enhancer function.

PMID- 16806969
TI  - Protein expression and preliminary crystallographic analysis of amino-terminal
      fragment of urokinase-type plasminogen activator.
AB  - The amino-terminal fragment (ATF, Ser1-Glu143) of urokinase-type plasminogen
      activator (uPA) is responsible for some important functions of uPA, such as
      receptor binding and chemotactic activity. To dissect the function and structure
      activity relationship of ATF, recombinant human ATF was expressed in Pichia
      pastoris system at a yield of about 30 mg/L. The recombinant ATF was captured by
      a cation exchange column, further purified up to 99% purity by a gel filtration
      column, and characterized in terms of its receptor binding capability. The
      purified ATF was then crystallized by the method of sitting-drop vapor diffusion
      with magnesium sulfate as the precipitating agent at 298 K. The crystals belong
      to space group P1 with unit cell dimensions of a=47.5A, b=64.7A, c=65.4A,
      alpha=71.6 degrees , beta=92.1 degrees , gamma=84.0 degrees .

PMID- 16806970
TI  - De novo design of a two-stranded coiled-coil switch peptide.
AB  - The properties and characteristics shared by amyloid fibrils formed from disease
      and non-disease associated proteins that are unrelated in sequence and structure
      offer the prospect that model systems can be used to systematically assess the
      factors that predispose a native protein to form amyloid fibrils. Based on a de
      novo design approach, we recently reported a unique switch peptide model system,
      ccbeta, that forms a three-stranded coiled-coil structure at low temperatures and
      which can be easily converted to amyloid fibrils by increasing the temperature.
      To simplify the system further, we describe here the redesign of a two-stranded
      ccbeta coiled-coil variant and its detailed analysis by a variety of biophysical
      methods. Compared with the original design, the characteristics of the peptide
      make it even simpler to elucidate and validate fundamental principles of amyloid
      fibril-formation.

PMID- 16806971
TI  - Expression of Mx mRNA following infection with IPNV is greater in IPN-susceptible
      Atlantic salmon post-smolts than in IPN-resistant Atlantic salmon parr.
AB  - The Mx response was compared in parr and post-smolt Atlantic salmon following
      intra-peritoneal injection of the same dose of Infectious Pancreatic Necrosis
      Virus (IPNV) per g of fish. Mx gene expression, measured by quantitative RT-PCR
      in liver, showed a maximum level 3days after injection in parr with undetectable
      levels on day 7. In post-smolts, similar levels as in parr were attained on day
      3, but levels then continued to rise on day 5 and 7 to about 10 times higher than
      the peak level in parr. Poly I:C injected parr showed Mx levels similar to IPNV
      injected post-smolts. Mortality from IPN in post-smolts occurred on days 6 and 7.
      Levels of IPN VP2 transcripts in parr were very low and did not increase with
      time, suggesting viral replication was low. Individual variation in levels of Mx
      and IPN VP2 gene transcripts was very high in post-smolts and although data is
      limited there was an inverse relationship between the levels of Mx and VP2,
      suggesting that individuals with high Mx levels on day 5 may be able to prevent
      viral replication. This contrasts with the response in parr, where IPN-resistance
      was not associated with a high Mx response.

PMID- 16806972
TI  - Expression kinetics of interferon and interferon-induced genes in Atlantic salmon
      (Salmo salar) following infection with infectious pancreatic necrosis virus and
      infectious salmon anaemia virus.
AB  - Infectious pancreatic necrosis virus (IPNV) and infectious salmon anaemia virus
      (ISAV) are economically important pathogens of the salmonid aquaculture industry.
      Atlantic salmon were challenged by intraperitoneal injection (i.p.) with either
      virus followed by time-course sampling. Cohabiting fish in the IPNV challenge
      were also sampled. Kidney tissue was analysed using a TaqMan real-time PCR assay
      to measure the expression of a range of host immune genes in relation to the
      endogenous control, elongation factor 1 alpha (ELF). Host genes measured included
      Mx, type I and type II interferon (IFN), gammaIFN induced protein (gammaIP),
      interleukin-1 beta (IL-1beta) and tumour necrosis factor alpha (TNF-alpha). Viral
      levels were also measured. In i.p. injected fish, both viruses greatly induced
      expression of Mx, gammaIP, type I and type II IFN by day 6 post-infection,
      however only ISAV caused substantial mortality. Some differences between the
      expression kinetics produced by both viruses were noted. Infection with ISAV
      increased IL-1beta expression following day 6, but no effect was seen in fish
      infected with IPNV. Neither virus induced TNF-alpha expression. This study
      confirms the presence of both type I and type II IFN responses and their induced
      genes in Atlantic salmon upon infection with an orthomyxovirus and a birnavirus.

PMID- 16806973
TI  - Gender effects on trapezius surface EMG during delayed onset muscle soreness due
      to eccentric shoulder exercise.
AB  - The purpose of this study was to investigate gender-specific motor control
      strategies during eccentric exercise and delayed onset muscle soreness (DOMS) in
      the shoulder region. Twelve healthy males and females participated in the study.
      Eccentric shoulder exercises were conducted on the dominant shoulder while the
      other side served as control. The exerted force, range of shoulder elevation,
      rating of perceived exertion, pain intensity, and surface electromyography (EMG)
      from the trapezius muscles were recorded and analyzed. A significant decrease in
      exerted force during exercise was only found in males despite similar rating of
      perceived exertion among genders. During eccentric exercise: males showed
      increasing root mean square (RMS) of the EMG while a decrease occurred for
      females, no difference between genders in mean power frequency of the EMG were
      seen. During static and dynamic contractions: no differences between genders in
      pain intensity or RMS were observed; RMS of the exercised side were lower than
      that of the control side (P<0.05) at 24 h after exercise. The results indicated a
      more prominent muscle fatigue resistance in females compared with males and
      mobilization of different muscle activation strategies during eccentric exercise.
      A protective adaptation to DOMS, i.e. decrease in RMS values was found with no
      gender differences.

PMID- 16806974
TI  - Strength and fatigability of selected muscles in upper limb: assessing muscle
      imbalance relevant to tennis elbow.
AB  - PURPOSE: The aetiology of tennis elbow has remained uncertain for more than a
      century. To examine muscle imbalance as a possible pathophysiological factor
      requires a reliable method of assessment. This paper describes the development of
      such a method and its performance in healthy subjects. We propose a combination
      of surface and fine-wire EMG of shoulder and forearm muscles and wrist strength
      measurements as a reliable tool for assessing muscle imbalance relevant to the
      pathophysiology of tennis elbow. METHODS: Six healthy volunteers participated.
      EMG data were acquired at 50% maximal voluntary isometric contraction from five
      forearm muscles during grip and three shoulder muscles during external rotation
      and abduction, and analysed using normalized median frequency slope as a fatigue
      index. Wrist extension/flexion strength was measured using a purpose-built
      dynamometer. RESULTS: Significant negative slope of median frequency was found
      for all muscles, with good reproducibility, and no significant difference in
      slope between the different muscles of the shoulder and the wrist. (Amplitude
      slope showed high variability and was therefore unsuitable for this purpose.)
      Wrist flexion was 27+/-8% stronger than extension (mean+/-SEM, p=0.006).
      CONCLUSION: This is a reliable method for measuring muscle fatigue in forearm and
      shoulder. EMG and wrist strength studies together can be used for assessing and
      identifying the muscle balance in the wrist-forearm-shoulder chain.

PMID- 16806975
TI  - Modifications of brain tissue volumes in facioscapulohumeral dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD), a pathology primarily
      characterized by involvement of the muscles in the face, shoulder and upper arm,
      can be associated to several CNS disorders, including sensorineural hearing
      deficits, schizophrenia, epilepsy and mental retardation. Aim of our study was to
      verify if brain tissue volumes, as measured by segmentation of MRI studies, are
      altered in FSHD. Volumes of gray matter (GM), white matter (WM), and
      cerebrospinal fluid (CSF) were compared, taking into account head size age and
      sex, both globally (by multiple regression analysis) and regionally (by optimized
      voxel-based morphometry-VBM) in thirty patients with FSHD and 39 normal subjects
      (NS). FSHD patients had significantly lower GM volumes and higher CSF volumes (P
      < 10(-4)). GM loss showed a borderline correlation with clinical severity (P <
      0.05). Brain tissue volumes did not correlate with disease duration, size of the
      genetic deletion, age at onset and the presence at MRI of WM hyperintensities
      (detected in 4/22 patients). At VBM three clusters of GM loss were detected, in
      the left precentral cortex (Brodmann areas 6, 2 and 44, P < 10(-14) corrected for
      multiple comparisons at cluster level), in the anterior cingulate (Brodmann areas
      33, 24 and 11, P < 10(-4)) and in the right fronto-polar region (Brodmann area
      10, P < 5.10(-3)). To the best of our knowledge, this is the first study to
      demonstrate a reduction in GM volume in FSHD. We hypothesize that localized GM
      loss in FSHD is the consequence of a selective involvement of specific CNS
      structures.

PMID- 16806976
TI  - Gender differences in the neural correlates of response inhibition during a stop
      signal task.
AB  - We used functional magnetic resonance imaging to examine gender differences in
      the neural correlates of response inhibition during a stop signal task. The task
      has a frequent "go" signal to set up a pre-potent response tendency and a less
      frequent "stop" signal for subjects to withhold their response. A contrast in
      brain activation was made between successful and failed inhibitions for
      individual subjects. We compared 20 men and 20 women matched in age and years of
      education and in stop signal performance, with stop success rate, post-error
      slowing and task-related frustration ratings as covariates. The results showed
      greater activation in men, compared to women, in a wide array of cortical and
      subcortical areas, including the globus pallidus and motor thalamus during stop
      signal inhibition. In contrast, no brain regions demonstrated greater activation
      in women, even at a lower statistical threshold. Moreover, while men activated
      the medial superior frontal and anterior cingulate cortices, women activated the
      caudate tail to mediate response inhibition. These results extended gender
      differences in regional brain activation to response inhibition during a
      cognitive motor task. Men activated the motor circuitry while women appeared to
      involve visual association or habit learning during stop signal performance.

PMID- 16806977
TI  - Multiple brain networks for visual self-recognition with different sensitivity
      for motion and body part.
AB  - Multiple brain networks may support visual self-recognition. It has been
      hypothesized that the left ventral occipito-temporal cortex processes one's own
      face as a symbol, and the right parieto-frontal network processes self-image in
      association with motion-action contingency. Using functional magnetic resonance
      imaging, we first tested these hypotheses based on the prediction that these
      networks preferentially respond to a static self-face and to moving one's whole
      body, respectively. Brain activation specifically related to self-image during
      familiarity judgment was compared across four stimulus conditions comprising a
      two factorial design: factor Motion contrasted picture (Picture) and movie
      (Movie), and factor Body part a face (Face) and whole body (Body). Second, we
      attempted to segregate self-specific networks using a principal component
      analysis (PCA), assuming an independent pattern of inter-subject variability in
      activation over the four stimulus conditions in each network. The bilateral
      ventral occipito-temporal and the right parietal and frontal cortices exhibited
      self-specific activation. The left ventral occipito-temporal cortex exhibited
      greater self-specific activation for Face than for Body, in Picture, consistent
      with the prediction for this region. The activation profiles of the right
      parietal and frontal cortices did not show preference for Movie Body predicted by
      the assumed roles of these regions. The PCA extracted two cortical networks, one
      with its peaks in the right posterior, and another in frontal cortices; their
      possible roles in visuo-spatial and conceptual self-representations,
      respectively, were suggested by previous findings. The results thus supported and
      provided evidence of multiple brain networks for visual self-recognition.

PMID- 16806978
TI  - To modulate or not to modulate: differing results in uniquely shaped Williams
      syndrome brains.
AB  - Voxel based morphometry (VBM) studies of Williams syndrome (WS) have demonstrated
      remarkably consistent findings of reduced posterior parietal gray matter compared
      to typical controls. Other WS VBM findings have been inconsistent, however. In
      particular, different findings have been reported for hypothalamus and
      orbitofrontal gray matter regions. We examined a sample of 8 WS and 9 control
      adults and show that the hypothalamus and orbitofrontal cortex results depend on
      whether the images undergo Jacobian modulation. Deformation based morphometry
      (DBM) analysis demonstrated that major brain shape differences between the groups
      accounted for the Jacobian modulated gray matter findings. These results indicate
      that cautious interpretations of modulated gray matter findings are warranted
      when there are gross shape and size differences between experimental groups. This
      study demonstrates the importance of methodological choices towards understanding
      a disorder like WS, but also highlights the consistency of parietal lobe,
      orbitofrontal, and midbrain findings for this disorder across methodologies,
      participants, and research groups.

PMID- 16806979
TI  - MRI time series modeling of MS lesion development.
AB  - A mathematical model was applied to new lesion formation in multiple sclerosis,
      as apparent on frequent T2-weighted MRI. The pathophysiologically motivated two
      process model comprises two opposing nonlinear self-limiting processes, intended
      to represent degenerative and reparatory processes, respectively, investigating
      T2 activity from a dynamic/temporal rather than a spatial/static perspective.
      Parametric maps were obtained from the model to characterize the MRI dynamics of
      lesion development, answering the questions of how long new T2 lesion activity
      persists, how much residual damage/hyperintensity remains and how the T2 dynamics
      compare to those of contrast-enhancing MRI indicating active inflammation. 997
      MRI examinations were analyzed, acquired weekly to monthly from 45 patients over
      a 1-year period. The model was applied to all pixels within 332 new lesions,
      capturing the time profiles with excellent fidelity (r = 0.89 +/- 0.03 average
      correlation between model and image data). From this modeling perspective, the
      observed dynamics in new T2 lesions are in agreement with two opposing processes
      of longitudinal intensity change, such as inflammation and degeneration versus
      resorbtion and repair. On average, about one third of a new lesion consisted of
      transient signal change with little or no residual hyperintensity and activity of
      10 weeks or less. Global lesion burden as MRI surrogate of disease activity may
      therefore be confounded by large amounts of transient hyperintensity. T2 activity
      also persisted significantly beyond the period of contrast enhancement, thereby
      defining MRI sensitivity toward a subacute phase of lesion development beyond
      blood-brain barrier patency. Concentric patterns of dynamic properties within a
      lesion were observed, consistent with concentric histological appearance of
      resulting MS plaques.

PMID- 16806980
TI  - Improving whole brain structural MRI at 4.7 Tesla using 4 irregularly shaped
      receiver coils.
AB  - Both higher magnetic field strengths (> or =3 T) and multiple receiver "array
      coils" can provide increased signal-to-noise ratio (SNR) for MRI. This increase
      in SNR can be used to obtain images with higher resolution, enabling better
      visualisation of structures within the human brain. However, high field strength
      systems also suffer from increased B(1) non-uniformity and increased power
      deposition, reaching specific absorption rate (SAR) limits more quickly. For
      these problems to be mitigated, a careful choice of both the pulse sequence
      design and transmit RF coil is required. This paper describes the use of a
      prototype array coil consisting of 4 irregularly shaped coils within a standard
      configuration for neuroimaging at 4.7 T (a head transmit/receive volume coil to
      minimise SAR and a head gradient insert for maximum gradient performance). With a
      fast spin echo (FSE) pulse sequence optimised for 4.7 T, this provides
      dramatically increased quality and resolution over a large brain volume. Using
      the array coil, a SNR improvement relative to the volume coil of 1-1.5 times in
      central brain areas and 2-3 times in cortical regions was obtained. Array coil
      images with a resolution of 352 x 352 x 2000 mum had a SNR of 16.0 to 26.2 in
      central regions and 19.9 to 34.8 in cortical areas. Such images easily
      demonstrate cortical myeloarchitecture, while still covering most of the brain in
      a approximately 12 min scan.

PMID- 16806981
TI  - A1 adenosine receptor PET using [18F]CPFPX: displacement studies in humans.
AB  - BACKGROUND: Imaging of cerebral A(1) adenosine receptors (A(1)AR) with positron
      emission tomography (PET) has recently become available for neurological
      research. To date, it has still not been unraveled if there is a valid reference
      region without specific radioligand binding that may be used to improve image
      quantification. We conducted in vivo displacement studies in humans to elucidate
      this important question using the A(1)AR ligand [(18)F]CPFPX. METHODS: Five
      healthy male volunteers underwent [(18)F]CPFPX bolus/infusion PET with short
      infusion of unlabelled CPFPX as competitor (n = 4; 0.9 to 4.0 mg) or vehicle (n =
      1; control condition) after equilibrium of [(18)F]CPFPX distribution was
      attained. RESULTS: Infusion of CPFPX induced a rapid displacement of [(18)F]CPFPX
      binding in all regions, including the cerebellum (region with lowest binding).
      Even at the highest competitor dose, no full displacement was reached.
      Displacement was dose-dependent in all regions except the cerebellum where floor
      effects and/or noise might have obscured dose dependency. Specific binding was
      estimated to account for about one third and two thirds of total equilibrium
      uptake in cerebellum and cortex, respectively. CONCLUSIONS: Although the
      cerebellum is the region with lowest in vivo [(18)F]CPFPX binding, it is not an
      ideal reference region devoid of specific binding. Nevertheless, as will be
      discussed, the use of a reference region analysis may be a useful, non-invasive
      alternative analysis method in carefully selected applications.

PMID- 16806982
TI  - Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis.
AB  - Brain atrophy measured by MRI is an important correlate with clinical disability
      and disease duration in multiple sclerosis (MS). Unfortunately, neuropathologic
      mechanisms which lead to this grey matter atrophy remain unknown. The objective
      of this study was to determine whether brain atrophy occurs in the mouse model,
      experimental autoimmune encephalomyelitis (EAE). Postmortem high-resolution T2
      weighted magnetic resonance microscopy (MRM) images from 32 mouse brains (21 EAE
      and 11 control) were collected. A minimum deformation atlas was constructed and a
      deformable atlas approach was used to quantify volumetric changes in
      neuroanatomical structures. A significant decrease in the mean cerebellar cortex
      volume in mice with late EAE (48-56 days after disease induction) as compared to
      normal strain, gender, and age-matched controls was observed. There was a direct
      correlation between cerebellar cortical atrophy and disease duration. At an early
      time point in disease, 15 days after disease induction, cerebellar white matter
      lesions were detected by both histology and MRM. These data demonstrate that
      myelin-specific autoimmune responses can lead to grey matter atrophy in an
      otherwise normal CNS. The model described herein can now be used to investigate
      neuropathologic mechanisms that lead to the development of gray matter atrophy in
      this setting.

PMID- 16806983
TI  - Effect of brain tumor neovasculature defined by rCBV on BOLD fMRI activation
      volume in the primary motor cortex.
AB  - We utilized blood oxygenation level dependent (BOLD) functional magnetic
      resonance imaging (fMRI) and MR perfusion imaging methods to study the influence
      of brain tumor neovascularity on the BOLD fMRI activation volume in the primary
      motor cortex (PMC). The results from 57 brain tumor cases demonstrated that, for
      grade IV gliomas only, decreases in the BOLD fMRI activation volumes within the
      ipsilateral PMC, when compared with that observed in the contralateral PMC,
      correlated with increases in the relative regional cerebral blood volume (rCBV)
      in the PMC. In addition, relative increases in the activation volumes,
      corresponding to decreases in the rCBV, exhibited a linear dependence on the
      distance between the grade IV glioma and PMC. These findings lend support to the
      hypothesis that decreases in the fMRI activation volumes adjacent to a GBM may,
      in part, be due to the increased contribution of aberrant tumor neovascularity,
      with the resultant de-coupling of blood flow from neuronal activity. The nature
      of the relationship between the resulting activation volumes and adjacent tumor
      characteristics is complex, but is found to be dependent on the tumor grade and
      type, as well as the distance of the tumor to the PMC.

PMID- 16806984
TI  - Does healthy aging affect the hemispheric activation balance during paced index
      to-thumb opposition task? An fMRI study.
AB  - Normal aging is generally associated with declining performance in cognitive and
      fine motor tasks. Previous functional imaging studies have been inconsistent
      regarding the effect of aging on primary motor cortex (M1) activation during
      finger movement, showing increased, unchanged or decreased activation
      contralaterally, and more consistently increased activation ipsilaterally.
      Furthermore, no study has addressed the effect of age on M1 hemispheric
      activation balance. We studied 18 optimally healthy right-handed subjects, age
      range 18-79 years (mean +/- SD: 47 +/- 17) using 3 T fMRI and right index finger
      thumb tapping auditory-paced at 1.25 Hz. The weighted Laterality Index (wLI) for
      M1 was obtained according to Fernandez et al. (2001) [Fernandez, G., de Greiff,
      A., von Oertzen, J., Reuber, M., Lun, S., Klaver, P., et al. 2001. Language
      mapping in less than 15 min: real-time functional MRI during routine clinical
      investigation. Neuroimage 14 585-594], with some modifications. The wLI, as well
      as the total activation on each side, were assessed against age using non
      parametric correlation. There was a highly significant negative correlation
      between age and wLI such that the older the subjects, the lower the wLI.
      Furthermore, there was a highly significant positive correlation between total
      activation for ipsilateral M1 and age, and a nearly significant trend for
      contralateral M1. This study documents that during execution of a simple paced
      motor task, the older the subject the less lateralized the M1 activation balance
      as a result of increasing amount of activation on both sides, more significantly
      so ipsilaterally. Thus, in aging, enhanced M1 recruitment bilaterally is required
      to produce the same motor performance, suggesting a compensatory process. These
      findings are in line with cognitive studies indicating a tendency for the aging
      brain to reduce its functional lateralization, perhaps from less efficient
      transcallosal connections.

PMID- 16806985
TI  - Brain plasticity in recovery from stroke: an MEG assessment.
AB  - The aim of this paper was to deepen understanding about the role played by brain
      plasticity in obtaining clinical recovery. Eighteen patients, who had recovered
      partially or totally from dysfunctions due to a monohemispheric infarction within
      the middle cerebral artery territory, underwent magnetoencephalographic (MEG)
      recordings of rolandic areas cerebral activity both in rest state (spectral power
      properties) and in response to the electrical stimulation of the contralateral
      median nerve (M20 and M30 cortical sources). MEG evaluation was performed in
      acute (T0: mean 5 days from ischemic attach) and post-acute phase (T1: median 6
      months). At T1, all the inter-hemispheric asymmetries were reduced for both
      spontaneous and evoked activity parameters with respect to T0. In post-acute
      phase, lower cortical excitability, higher delta and theta power and lower
      spectral entropy were associated to a worse clinical state. An unusual
      recruitment-as revealed by an excessive inter-hemispheric asymmetry of M20
      cortical source position-correlated with higher level of clinical amelioration in
      the patients who showed a partial recovery. In addition to confirmative evidence
      that "normalization" of neural activity in both the affected and unaffected
      hemispheres subtends best clinical recovery, present data provide support to the
      positive role of cerebral plasticity phenomena--i.e. unusual neural recruitments-
      to regain lost functions in those patients unable to achieve total recovery.

PMID- 16806986
TI  - Exploring the visual world: the neural substrate of spatial orienting.
AB  - Inspecting the visual environment, humans typically direct their attention across
      space by means of voluntary saccadic eye movements. Neuroimaging studies in
      healthy subjects have identified the superior parietal cortex and intraparietal
      sulcus as important structures involved in visual search. However, in apparent
      contrast, spatial disturbance of free exploration typically is observed after
      damage of brain structures located far more ventrally. Lesion studies in such
      patients disclosed the inferior parietal lobule (IPL) and temporo-parietal
      junction (TPJ), the superior temporal gyrus (STG) and insula, as well as the
      inferior frontal gyrus (IFG) of the right hemisphere. Here we used functional
      magnetic resonance imaging to investigate the involvement of these areas in
      active visual exploration in the intact brain. We conducted a region of interest
      analysis comparing free visual exploration of a dense stimulus array with the
      execution of stepwise horizontal and vertical saccades. The comparison of BOLD
      responses revealed significant signal increases during exploration in TPJ, STG,
      and IFG. This result calls for a reappraisal of the previous thinking on the
      function of these areas in visual search processes. In agreement with lesion
      studies, the data suggest that these areas are part of the network involved in
      human spatial orienting and exploration. The IPL dorsally of TPJ seem to be of
      minor importance for free visual exploration as these areas appear to be equally
      involved in the execution of spatially predetermined saccades.

PMID- 16806987
TI  - Centrifugal regulation of human cortical responses to a task-relevant
      somatosensory signal triggering voluntary movement.
AB  - Many studies have reported a movement-related modulation of response in the
      primary and secondary somatosensory cortices (SI and SII) to a task-irrelevant
      stimulation in primates. In the present study, magnetoencephalography (MEG) was
      used to examine the top-down centrifugal regulation of neural responses in the
      human SI and SII to a task-relevant somatosensory signal triggering a voluntary
      movement. Nine healthy adults participated in the study. A visual warning signal
      was followed 2 s later by a somatosensory imperative signal delivered to the
      right median nerve at the wrist. Three kinds of warning signal informed the
      participants of the reaction which should be executed on presentation of the
      imperative signal (rest or extension of the right index finger, extension of the
      left index finger). The somatosensory stimulation was used to both generate
      neural responses and trigger voluntary movement and therefore was regarded as a
      task-relevant signal. The responses were recorded using a whole-head MEG system.
      The P35m response around the SI was reduced in magnitude without alteration of
      the primary SI response, N20m, when the signal triggered a voluntary movement
      compared to the control condition, whereas bilateral SII responses peaking at 70
      100 ms were enhanced and the peak latency was shortened. The peak latency of the
      responses in the SI and SII preceded the onset of the earliest voluntary muscle
      activation in each subject. Later bilateral perisylvian responses were also
      enhanced with movement. In conclusion, neural activities in the SI and SII evoked
      by task-relevant somatosensory signals are regulated differently by motor-related
      neural activities before the afferent inputs. The present findings indicate a
      difference in function between the SI and SII in somatosensory-motor regulation.

PMID- 16806988
TI  - Structural insights from high-resolution diffusion tensor imaging and
      tractography of the isolated rat hippocampus.
AB  - The hippocampus is a critical structure for learning and memory formation injured
      by diverse neuropathologies such as epilepsy or Alzheimer's disease. Recently,
      clinical investigations have attempted to use diffusion tensor MRI as a more
      specific surrogate marker for hippocampal damage. To first better understand the
      tissue architecture of healthy hippocampal regions, this study characterized 10
      rat hippocampi with diffusion tensor imaging (DTI) at 50-microm in-plane image
      resolution using a 14.1-T magnet. Chemical fixation of the dissected and
      straightened rat hippocampus provided a simple, effective way to reduce partial
      volume effects when segmenting hippocampal regions and improved mean signal-to
      noise per unit time (e.g. 50.6+/-4.4 at b=1250 s/mm2 in 27 min). Contrary to
      previous reports that water diffusion is homogeneous throughout the nervous
      system, statistically different mean diffusivities were observed (e.g. 0.238+/
      0.054 and 0.318+/-0.084 microm2/ms for the molecular and granule cell layers
      respectively) (ANOVA, P<0.05). Different hippocampal subregions had lower
      fractional anisotropy than uniformly fibrous structures like corpus callosum
      because of their complex architecture. DTI-derived color fiber orientation maps
      and tractography demonstrated most components of the trisynaptic intrahippocampal
      pathway (e.g. orientations in stratum lacunosum-moleculare were dominated by
      perforant and Schaffer fibers) and also permitted some assessment of connectivity
      in the rat hippocampus.

PMID- 16806991
TI  - Sicyopterus lagocephalus: widespread species, species complex, or neither? A
      critique on the use of molecular data for species identification.

PMID- 16806990
TI  - Contrasting patterns of genetic structure in two species of the coral trout
      Plectropomus (Serranidae) from east and west Australia: introgressive
      hybridisation or ancestral polymorphisms.
AB  - Inter-specific genetic relationships among regional populations of two species of
      grouper (Plectropomus maculatus and Plectropomus leopardus) were examined using
      mitochondrial and nuclear markers. mtDNA revealed contrasting regional inter
      specific patterns whilst nuclear markers revealed contrasting patterns among
      markers, irrespective of region. In eastern Australia (EA) the species form a
      single mtDNA lineage, but the two species are reciprocally monophyletic in
      Western Australia (WA). This supports previous evidence for hybridisation between
      these species on the east coast. WA P. leopardus forms a sister relationship with
      the EA P. leopardus-maculatus clade while WA P. maculatus is more basal and
      sister to the P. leopardus lineages, indicating mtDNA does not suffer from
      incomplete lineage sorting for these species. In contrast, one of three nuclear
      markers (locus 7-90TG) differentiated the species into two reciprocally
      monophyletic clades, with no evidence of hybridisation or ancestral polymorphism.
      The remaining two nuclear markers (2-22 and ETS-2) did not separate these two
      species, while distinguishing other plectropomid species, suggesting incomplete
      lineage sorting at these nuclear loci. These results together with coalescence
      analyses suggest that P. leopardus females have hybridised historically with P.
      maculatus males and that P. maculatus mitochondria were displaced through
      introgressive hybridisation and fixation in the P. maculatus founder population
      on the Great Barrier Reef. The contrasting regional patterns of mtDNA structure
      may be attributed to Quaternary sea-level changes and shelf width differences
      driving different reef configurations on each coast. These reef configurations
      have provided opportunities for local scale interaction and reproduction among
      species on the narrower EA continental shelves, but not on the broader WA
      continental shelves.

PMID- 16806989
TI  - Mapping an intrinsic MR property of gray matter in auditory cortex of living
      humans: a possible marker for primary cortex and hemispheric differences.
AB  - Recently, magnetic resonance properties of cerebral gray matter have been
      spatially mapped--in vivo--over the cortical surface. In one of the first
      neuroscientific applications of this approach, this study explores what can be
      learned about auditory cortex in living humans by mapping longitudinal relaxation
      rate (R1), a property related to myelin content. Gray matter R1 (and thickness)
      showed repeatable trends, including the following: (1) Regions of high R1 were
      always found overlapping posteromedial Heschl's gyrus. They also sometimes
      occurred in planum temporale and never in other parts of the superior temporal
      lobe. We hypothesize that the high R1 overlapping Heschl's gyrus (which likely
      indicates dense gray matter myelination) reflects auditory koniocortex (i.e.,
      primary cortex), a heavily myelinated area that shows comparable overlap with the
      gyrus. High R1 overlapping Heschl's gyrus was identified in every instance
      suggesting that R1 may ultimately provide a marker for koniocortex in
      individuals. Such a marker would be significant for auditory neuroimaging, which
      has no standard means (anatomic or physiologic) for localizing cortical areas in
      individual subjects. (2) Inter-hemispheric comparisons revealed greater R1 on the
      left on Heschl's gyrus, planum temporale, superior temporal gyrus and superior
      temporal sulcus. This asymmetry suggests greater gray matter myelination in left
      auditory cortex, which may be a substrate for the left hemisphere's specialized
      processing of speech, language, and rapid acoustic changes. These results
      indicate that in vivo R1 mapping can provide new insights into the structure of
      human cortical gray matter and its relation to function.

PMID- 16806992
TI  - Nuclear and mitochondrial sequence data reveal the major lineages of starlings,
      mynas and related taxa.
AB  - We investigated the phylogenetic relationships among the major lineages of the
      avian family Sturnidae and their placement within the Muscicapoidea clade using
      two nuclear (RAG-1 and myoglobin) and one mitochondrial gene (ND2). Among
      Muscicapoidea, we recovered three clades corresponding to the families Cinclidae,
      Muscicapidae and Sturnidae (sensu [Sibley, C.G., Monroe Jr., B.L., 1990.
      Distribution and Taxonomy of Birds of the World. Yale University Press, New
      Haven, CT]). Within the sturnoid lineage Mimini and Sturnini are sister groups,
      with Buphagus basal to them. We identified three major lineages of starlings: the
      Philippine endemic genus Rhabdornis, an Oriental-Australasian clade (genera
      Scissirostrum, Gracula, Mino, Ampeliceps, Sarcops, Aplonis), and an Afrotropical
      Palaearctic clade (all African taxa, Sturnus and Acridotheres). We discuss the
      biogeographic implications of our findings and suggest an Asiatic origin for this
      family. The congruence between the age of major clades, estimated by NPRS, and
      palaeoclimatic data present evidence for the role of climatic changes in shaping
      present day distribution of the group.

PMID- 16806993
TI  - Safety pharmacology in focus: new methods developed in the light of the ICH S7B
      guidance document.
AB  - 'Safety' continues to be a growth area in 'Pharmacology'. This issue of Journal
      of Pharmacological and Toxicological Methods is the third to be focused on
      methods development in the safety pharmacology area. The unusual nature of safety
      pharmacology mandates that methods development be done with, not only scientific
      validation, but also, adherence to the mandates of legislation to the forefront.
      This focused issue draws on a broad range of global safety pharmacology experts,
      many of whom operate in the industrial milieu. They have reviewed and updated
      current models, validated modifications, and have also introduced novel
      methodology important to the conduct of non-clinical safety pharmacology studies.
      The contributors were all active participants at the 5th Annual Safety
      Pharmacology Society (SPS) meeting held in Mannheim, Germany September 25-28,
      2005. The publications presented here describe in vitro and in vivo
      pharmacological methods development that has been informed by the S7A regulatory
      guidance document for pre-clinical safety testing of drugs. While S7A describes
      the 'core battery' of methods used to characterize the safety pharmacology
      profile of a compound, the most recent news in Safety Pharmacology involves
      ratification of the related S7B safety guidance document. Unlike the past, S7B
      heralds a new era for the pharmaceutical industry since it now sets out how to
      address safety concerns of a new chemical entity (NCE) in relation to adverse
      actions on ventricular repolarization, a topic that has vexed industry and
      regulatory authorities for many years. Unsurprisingly there are many papers in
      the present issue that address this specific aspect of safety pharmacology. These
      include results from the Health and Environmental Sciences Institute of the
      International Life Sciences Institute (ILSI/HESI) initiative, in which non
      clinical in vitro (hERG and Purkinje fiber) and in vivo (QT dog study) assays
      were found to be useful in the determination of drug-induced QT prolongation
      risk, and thus provide better characterization of a biomarker for the potential
      risk in humans for development of the torsades de pointes syndrome. However,
      safety methods development does not begin and end with ventricular
      repolarization. This focused issue also describes the re-evaluation and
      validation of a primate CNS model for evaluating orthostatic hypotension, and
      outlines a simple and rapid rodent object recognition task model that can be used
      to assess the amnesic potential of an NCE. Reviews of respiratory safety studies
      as well as both in vitro and in vivo aspects of cardiovascular function are also
      described. There are also papers that describe the pharmacology of vehicles and
      solvents used to solubilize study drugs and the applicability of voltage
      sensitive dyes to optically record cardiac action potentials from single
      myocytes. Thus, this issue of the Journal of Pharmacological and Toxicological
      Methods remains a primary resource for industrial and academic pharmacologists
      interested in better understanding non-clinical safety pharmacology methods.

PMID- 16806994
TI  - ACTH therapy for generalized seizures other than spasms.
AB  - PURPOSE: We reviewed our experience with ACTH for the treatment of intractable
      generalized seizures other than spasms. METHODS: Efficacy and adverse effects of
      ACTH against intractable generalized seizures other than spasms were
      retrospectively investigated in 15 patients treated between 1991 and 2003. The
      median age of the patients at ACTH therapy was 42 months. The targeted type of
      seizure was brief tonic in 6, atypical absence in 6, atonic in 2, and myoclonic
      in 1. The dose of ACTH was 0.01-0.015 mg/kg in most patients. The effect of ACTH
      was determined at the end of ACTH therapy, and 3 months and 1 year after ACTH
      therapy. RESULTS: Seizure freedom was obtained in 13 of 15 patients. However, 6
      of them had a recurrence of seizures within 3 months after ACTH therapy. ACTH was
      the most effective in patients with atypical absence seizures. Statistical
      analysis showed that the number of injection and total dose of ACTH were smaller
      in patients with atypical absence seizures than in those with brief tonic
      seizures. Adverse effects were frequent but serious one was not observed.
      CONCLUSION: ACTH therapy was effective in patients with intractable generalized
      seizures other than spasms. However, its efficacy was often transient. ACTH can
      be useful for generalized seizures other than spasms but its limitation should be
      considered.

PMID- 16806995
TI  - Electroclinical evolution in ring chromosome 20 epilepsy syndrome: a case with
      severe phenotypic features followed for 25 years.
AB  - Intractable epilepsy and peculiar EEG patterns characterize ring chromosome 20
      syndrome [r(20)], while dysmorphic features, mental retardation and behavioural
      disturbances are widely variable. The clinical evolution of r(20) over time is
      not well defined as relatively few cases have been reported. Here we describe a
      patient with severe clinical features followed for a 25-year period. The patient
      was subjected to clinical, psychometric and EEG evaluation twice a year from the
      age of 21 years. Cytogenetic studies, using chromosome analysis and fluorescence
      in situ hybridization (FISH) and several immunological investigations were
      performed. Ring chromosome 20 was found in 50% of examined metaphases with the
      deletion of subtelomeric regions 20p and 20q. Our patient presented with marked
      dysmorphic features, severe mental retardation, tetraparesis, dysarthria and
      intractable epilepsy with onset during the first year of life. During follow up,
      EEG findings and clinical features progressively worsened: a progressive
      disorganization of background EEG activity occurred and mental and motor
      impairment evolved. The severity of clinical expression depended on the extent of
      chromosomal deletion and on the haploinsufficiency of other important related
      genetic loci due to ring instability. The progressive worsening of both clinical
      and EEG features over a long period, which has also been reported by other
      authors, further characterized this syndrome.

PMID- 16806996
TI  - MRI of bone marrow edema-like signal in the pathogenesis of subchondral cysts.
AB  - OBJECTIVE: To determine if a relationship exists between bone marrow edema-like
      signal and subchondral cysts on magnetic resonance imaging (MRI). DESIGN:
      Retrospective cohort of 32 patients with two sequential knee MRI. Patients with
      acute trauma, infection, neoplasm, or osteonecrosis were excluded. The degree of
      osteoarthritis was assessed using an adaptation of the Baltimore Longitudinal
      Study of Aging (BLSA) scale. Initial and follow-up exams were reviewed for
      presence, location, size and changes of marrow edema-like signal, subarticular
      cysts and cartilage abnormality. All locations in the knee were aggregated for
      analysis with descriptive statistics. RESULTS: The mean time interval between
      exams was 17.52 months (range 2.1-40.1 months). There were 23 cysts: 11 (47.8%)
      new, 6 (26.1%) increased size, 1 (4.4%) decreased size, and 5 (21.7%) no change
      in pre-existing lesions. Cysts always arose from regions of marrow edema-like
      signal. There were 68 subarticular areas of marrow edema-like signal: 16 (23.5%)
      new, 23 (33.8%) increased size, 17 (25%) decreased size, 11 (16.2%) resolved and
      1 (1.5%) no change in pre-existing lesion. Marrow edema-like signal size always
      changed with cyst development: increased in 6/11 (54.5%), decreased in 2/11
      (18.1%) and resolved in 3/11 (27.2%). Change in cyst size was always accompanied
      by a change in edema-like signal size. An MRI visible cartilage abnormality was
      adjacent to 87% (20/23) of cysts. The mean BLSA score changed from 2.6 to 3.6
      indicating an overall progression of osteoarthritis. CONCLUSION: Subchondral
      cysts develop in pre-existing regions of subchondral bone marrow edema-like
      signal.

PMID- 16806997
TI  - The cleavage of biglycan by aggrecanases.
AB  - OBJECTIVE: Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin
      motifs (ADAMTS)-4] and aggrecanase-2 (ADAMTS-5) have been named for their ability
      to degrade the proteoglycan aggrecan. While this may be the preferred substrate
      for these enzymes, they are also able to degrade other proteins. The aim of this
      work was to determine whether the aggrecanases could degrade biglycan and
      decorin. METHODS: Biglycan, decorin and aggrecan were purified from human and
      bovine cartilage and subjected to degradation by recombinant aggrecanase-1 or
      aggrecanase-2. In vitro degradation was assessed by sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) and immunoblotting, and the
      cleavage site in biglycan was determined by N-terminal amino acid sequencing.
      SDS/PAGE and immunoblotting were also used to assess in situ degradation in both
      normal and arthritic human articular cartilage. RESULTS: Both aggrecanase-1 and
      aggrecanase-2 are able to cleave bovine and human biglycan at a site within their
      central leucine-rich repeat regions. Cleavage occurs at an asparagine-cysteine
      bond within the fifth leucine-rich repeat. In contrast, the closely related
      proteoglycan decorin is not a substrate for the aggrecanases. Analysis of human
      articular cartilage from osteoarthritic (OA) and rheumatoid arthritic (RA) joints
      showed that a biglycan degradation product of equivalent size is present in the
      extracellular matrix. No equivalent degradation product was, however, detectable
      in normal adult human articular cartilage. CONCLUSION: Biglycan, which is
      structurally unrelated to aggrecan, can act as a substrate for aggrecanase-1 and
      aggrecanase-2, and these proteinases may account for at least part of the
      biglycan degradation that is present in arthritic cartilage.

PMID- 16806998
TI  - High molecular weight hyaluronic acid down-regulates the gene expression of
      osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes
      from patients with early osteoarthritis.
AB  - OBJECTIVE: Activated synoviocytes play important roles in the progression of
      human osteoarthritis (OA). Intra-articular injection of high molecular weight
      hyaluronic acid (HMW-HA) has been used as viscosupplementation for knee OA but
      its effect on synoviocytes remains undisclosed. This study aims to investigate
      the effects of HMW-HA on the gene expression of 16 OA-associated cytokines and
      enzymes, including interleukin (IL)-1beta, IL-6, IL-8, leukemia inhibitory factor
      (LIF), tumor necrosis factor (TNF)-alpha, TNF-alpha converting enzyme (TACE),
      matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor
      of metalloproteinase (TIMP)-1, TIMP-2, aggrecanase-1, aggrecanase-2, and
      inducible nitric oxide synthase (iNOS), in fibroblast-like synoviocytes (FLS)
      from patients with early stage OA. METHOD: Synovial fluid-derived FLS were
      obtained from the knees of 15 patients with early stage OA. IL-1-stimulated or
      unstimulated FLS were cultured with or without the treatment of 600-800kDa HMW
      HA. Moreover, blocking experiments with anti-CD44 monoclonal antibodies (mAb)
      were used to examine the involvement of CD44 in HMW-HA effects. We designed and
      validated the real-time quantitative polymerase chain reaction (Q-PCR) assays
      with SYBR Green dyes for simultaneous quantification of the expression of the 16
      genes. RESULTS: HMW-HA down-regulated IL-8 and iNOS gene expression in
      unstimulated FLS and down-regulated aggrecanase-2 and TNF-alpha gene expression
      in IL-1-stimulated FLS. CD44 blocking inhibited the down-regulatory effects of
      HMW-HA on gene expression. CONCLUSION: HMW-HA may have a structure-modifying
      effect for OA by down-regulation of aggrecanase-2 in FLS. HMW-HA also has an anti
      inflammatory effect by down-regulation of TNF-alpha, IL-8, and iNOS in FLS. These
      effects may be mediated through the interaction of CD44 and HMW-HA.

PMID- 16806999
TI  - N-all-trans-retinoyl-L-proline inhibits metastatic potential of hepatocellular
      carcinoma cells.
AB  - Tumor metastasis is usually a serious problem in tumor patients because of the
      lack of therapeutic approaches. A new compound, N-all-trans-retinoyl-L-proline
      (ATRP), has been developed and its metastasis inhibition activity has been
      studied. Low concentrations of ATRP have already been found to inhibit
      hepatocellular carcinoma cells (HCC) in a dose- and time-dependent manner by
      inducing the expression of p27(kip). We found that ATRP inhibited metastasis
      associated behaviors in Hep3B cells, such as cell migration, invasion, collagen
      adhesion and gelatinase expression, more significantly than retinoic acid.
      Further, such inhibitory activities were observed in the regulation of cellular
      surface fucosylated epitope functions, such as binding of ulex europaeus lectin,
      expression of Lewis x, y and b, and activity of alpha1,3 fucosyltransferase.
      Hep3B cells pretreated with ATRP showed a significantly reduced incidence of
      experimental intrahepatic metastasis in nude mice. We conclude that ATRP is an
      alternative inhibitor and potential therapeutic agent for HCC metastasis with a
      different mechanism of action from ATRP.

PMID- 16807000
TI  - Experience with songs in adulthood reduces song-induced gene expression in
      songbird auditory forebrain.
AB  - Male songbirds learn to produce song within a limited phase early in life;
      however they continue to learn to recognize songs in adulthood. Studies looking
      at Zenk activation after exposure to songs learned early in life for song
      production and songs learned in adulthood show opposite patterns of activation,
      suggesting distinct neural mechanisms may be involved in these two forms of
      learning. In this study, we look at IEG Zenk activation in auditory regions NCM
      and CMM of song sparrows (Melospiza melodia) to see whether recent exposure to
      song in adulthood leads to greater or decreased Zenk activation upon hearing that
      song versus a novel song. We found significantly lower activation in birds
      exposed to previously heard songs versus novel songs in vNCM but not dNCM, though
      further analysis suggest an overall trend in NCM. We found no significant
      difference in the amount of activation to previously heard songs vs. novel songs
      in CMM. These results support previous findings suggesting that activation is
      reduced to learned stimuli; we discuss possible implications of these findings in
      relation to song production learning early in life and song recognition learning
      in adulthood.

PMID- 16807001
TI  - Fluoropolymer-coated dacron versus PTFE grafts for femorofemoral crossover
      bypass: randomised trial.
AB  - OBJECTIVES: To investigate whether patency of a thin walled 8 mm fluoropassivated
      Dacron graft was similar to that of a standard 8mm PTFE graft for femorofemoral
      crossover bypass surgery. DESIGN: A randomised multicentre clinical trial
      comparing two vascular grafts with participation of 10 departments of vascular
      surgery in Denmark, Sweden and Norway. PATIENTS AND METHODS: 198 patients were
      randomised to PTFE (n=107) or fluoropolymer-coated Dacron grafts (n=91), 63%
      underwent surgery for claudication, 27% for ischaemic rest pain and 10% for
      tissue loss. The median follow-up time was 24 months (IQR 19-26 months). RESULTS:
      The primary patency rate of the two grafts was similar (log rank test: p=0.35).
      The primary patency rates (95% CI) for coated Dacron and PTFE grafts were 92% (86
      98) and 94% (89-99) at 12 months and 87% (74-95) and 93% (87-99) at 24 months,
      respectively. CONCLUSION: In patients with unilateral iliac artery disease not
      amenable to angioplasty, the femoral-femoral bypass is durable and effective. No
      difference in patency was found between the two graft materials (fluoropolymer
      coated Dacron and PTFE).

PMID- 16807002
TI  - Hydra, a niche for cell and developmental plasticity.
AB  - The silencing of genes whose expression is restricted to specific cell types
      and/or specific regeneration stages opens avenues to decipher the molecular
      control of the cellular plasticity underlying head regeneration in hydra. In this
      review, we highlight recent studies that identified genes involved in the
      immediate cytoprotective function played by gland cells after amputation; the
      early dedifferentiation of digestive cells into blastema-like cells during head
      regeneration, and the early late proliferation of neuronal progenitors required
      for head patterning. Hence, developmental plasticity in hydra relies on spatially
      restricted and timely orchestrated cellular modifications, where the functions
      played by stem cells remain to be characterized.

PMID- 16807003
TI  - Two different evolutionary origins of stem cell systems and their molecular
      basis.
AB  - We propose two major evolutionary origins of stem cell systems in the animal
      kingdom. Adult pluripotent stem cell systems are found in many invertebrates and
      probably evolved as components of asexual reproduction. Lineage-specific stem
      cell systems probably evolved later and include neural and hematopoietic stem
      cell types. We propose that these two types of stem cell systems evolved
      independently. The vasa-like genes regulate reproductive stem cells, but not
      lineage-specific stem cells, which may be regulated by gcm genes. Here, we review
      the evidence for the molecular basis for the evolutionary origin of these two
      different stem cell systems.

PMID- 16807004
TI  - The stem cell concept in sponges (Porifera): Metazoan traits.
AB  - Sponges are considered the oldest living animal group and provide important
      insights into the earliest evolutionary processes in the Metazoa. This paper
      reviews the evidence that sponge stem cells have essential roles in cellular
      specialization, embryogenesis and Bauplan formation. Data indicate that sponge
      archaeocytes not only represent germ cells but also totipotent stem cells. Marker
      genes have been identified which are expressed in totipotent stem cells and
      gemmule cells. Furthermore, genes are described for the three main cell lineages
      in sponge, which share a common origin from archaeocytes and result in the
      differentiation of skeletal, epithelial, and contractile cells.

PMID- 16807005
TI  - Formation of glomerular maps in the olfactory system.
AB  - Sensory perception relies on the decoding of external stimuli into an internal
      neuronal representation, which requires precise connections between the periphery
      and the brain. In the olfactory system the axons of chemosensory neurons with the
      same odorant receptor coalesce into common glomeruli in the olfactory bulb,
      forming a receptor-topic map. The creation of this map begins prenatally when
      axons navigate towards the bulb, resort in a receptor-specific manner and
      terminate in a broad area interdigitated with other axon populations; distinct
      glomeruli form postnatally. While the initial process of glomerulization requires
      mainly molecular determinants, activity-dependent processes lead to a refinement
      of glomerular organization.

PMID- 16807006
TI  - Recommendations and supporting evidence in guidelines for referral of patients to
      sleep laboratories.
AB  - At the request of Canadian health ministries, we reviewed recommendations in
      guidelines prepared by professional bodies on the referral of individuals to
      sleep laboratories. Searching electronic databases and the Internet, we found 37
      guidelines that covered 18 applications of sleep laboratory investigation
      including obstructive sleep apnea, other respiratory disorders, obstructive sleep
      apnea and other conditions in children, sudden infant death syndrome, treatment
      for snoring, insomnia, depression with insomnia, narcolepsy, restless legs
      syndrome/periodic limb movement disorder, parasomnias and circadian rhythm
      disorders. We identified recommendations on referral of patients for sleep
      studies and assessed the quality and relevance of evidence cited in support of
      these. Of 81 recommendations, 46 were supported by evidence from primary
      investigations. Only six cases cited evidence from well-conducted, prospective
      controlled studies. Evidence was highly relevant in 18 cases, of some relevance
      in 22 and of little or no relevance in six. No evidence was provided in support
      of 31 recommendations, and in four cases the guideline had identified an absence
      of available evidence. Although the publications from professional bodies that
      were reviewed contain much detailed information, evidence supporting many
      recommendations is limited. There is a need for further, good quality, studies of
      many sleep laboratory applications.

PMID- 16807007
TI  - Neurophysiological aspects of primary insomnia: implications for its treatment.
AB  - Insomnia has usually been studied from a behavioral perspective. Somatic and/or
      cognitive conditioned arousal was shown to play a central role in sleep
      complaints becoming chronic, and was used as a starting point for the development
      of treatment modalities. The introduction of the neurocognitive perspective, with
      its focus on cortical or CNS arousal, has given rise to a renewed interest in the
      neurophysiological characteristics of insomnia. Recent research, using
      quantitative EEG, neuroimaging techniques and the study of the microstructure of
      sleep, suggests a state of hyperarousal with a biological basis. Furthermore,
      insomnia might not be restricted to sleep complaints alone because it appears to
      be a 24-h disorder, affecting several aspects of daytime functioning as well.
      These new findings have implications for the treatments used and indicate that a
      focus on cortical or CNS arousal should be pursued. As such, the use of EEG
      neurofeedback, a self-regulation method based on the paradigm of operant
      conditioning, might be a promising treatment modality. Preliminary results for
      insomnia and successful applications for other disorders suggest that this
      treatment can have the necessary stabilizing effects on the EEG activity,
      possibly resulting in a normalizing effect on daytime as well as nighttime
      functioning.

PMID- 16807008
TI  - Light-dependent regulation of the gene cut-1 of Neurospora, involved in the
      osmotic stress response.
AB  - The gene cut-1 from Neurospora encodes a protein of the haloacid dehalogenase
      (HAD) family, a group of enzymes usually associated to phosphatase or
      phosphotransferase activities. Loss of cut-1 function results in an osmosensitive
      phenotype and its transcription is induced by high osmotic pressure or heat
      shock, but not by other stressing conditions tested. Unexpectedly, cut-1
      transcript levels markedly decrease following illumination in the wild type and
      in some mutants tested, such as bd and vvd. The reduction was less pronounced in
      wc-1 and wc-2 mutants, indicating that this photoresponse is principally mediated
      by the WC system, a conclusion further supported by the lack of effect of blue
      light in a wc-1 mutant. Additionally, cut-1 mRNA levels are much higher in the
      dark in wc, vvd, bd, and cut mutants, showing the involvement of these genes in a
      cut-1 down-regulation mechanism. In the cases investigated, the mRNA levels of
      these strains increased further under high osmotic conditions, indicating an
      independent derepression effect. The environmental or genetic factors influencing
      cut-1 expression have no significant effect on the mRNA levels of two additional
      Neurospora genes encoding HAD proteins.

PMID- 16807009
TI  - Stress and acute phase protein response: an inconspicuous but essential linkage.

PMID- 16807010
TI  - Pharmacokinetic behavior and pharmacokinetic/pharmacodynamic integration of
      marbofloxacin after subcutaneous administration in goats.
AB  - The pharmacokinetic behavior of marbofloxacin was studied in goats after single
      dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in
      plasma was determined by high performance liquid chromatography and the data
      obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak
      plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h
      (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area
      under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively.
      Taking into account the values obtained for the efficacy indices, it was
      concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to
      treat infections caused by high susceptible bacteria like Escherichia coli or
      Salmonella spp.

PMID- 16807011
TI  - Clinical variation in melioidosis in pigs with clonal infection following
      possible environmental contamination from bore water.
AB  - An outbreak of melioidosis occurred in pigs on a rural property in the tropical
      north of the Northern Territory of Australia. The pigs were mostly asymptomatic
      but lesions in the parotid glands suggested an oral route of infection. Skin
      lesions were also common and one piglet had disseminated infection. Pulsed-field
      gel electrophoresis showed an identical pattern amongst Burkholderia pseudomallei
      isolates from the pigs, with similarity to an isolate from the unchlorinated bore
      water supplying the property.

PMID- 16807012
TI  - Carcass condemnation causes of growth retarded pigs at slaughter.
AB  - Condemnation causes of growth retarded pigs were studied in a Spanish abattoir. A
      total of 513 carcasses out of 6017 (8.5%) were rejected during inspection. The
      main reasons for condemnation were abscesses, cachexia, catarrhal
      bronchopneumonia, vertebral osteomyelitis, arthritis, pleuritis, peritonitis and
      pleuropneumonia. Positive relationships were found between tail lesions and
      arthritis (OR=5.23) or vertebral osteomyelitis (OR=24.81), while no relationships
      were found between tail lesions and abscesses. Lower risks were observed among
      carcasses condemned for cachexia, and were as follows: abscesses (OR=0.18),
      arthritis (OR=0.32), vertebral osteomyelitis (OR=0.06). Arcanobacterium pyogenes,
      either alone or in combination with other agents, was the main bacterial species
      isolated from abscesses, osteomyelitis and arthritis (73.5% of lesions). Direct
      economical losses associated with condemnation were calculated to be 30,000 Euro.

PMID- 16807013
TI  - Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain.
AB  - In this study we investigated the role of endothelin-1 (ET-1) and its peripheral
      receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors
      were induced in the hind paw of female mice by local injection of cells derived
      from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated
      by reduction in withdrawal thresholds in response to mechanical stimulation,
      began at four days after SCC inoculation and lasted to 28 days, the last day of
      measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were
      significantly upregulated compared to normal tissue, and local administration of
      the ET-A receptor selective antagonist, BQ-123 (100 microM) significantly
      elevated withdrawal thresholds, indicating the induction of an antinociceptive
      effect. These findings support the suggestion that ET-1 and ET-A receptors
      contribute to the severity of carcinoma-induced soft tissue cancer pain.

PMID- 16807015
TI  - Revisiting the initial rate approximation in kinetic NOE measurements.
AB  - The nuclear Overhauser effect (NOE) is undoubtedly one of the most useful tools
      in NMR spectroscopy and is widely used in solving structural and conformational
      problems of small organic molecules and macromolecular systems alike. In
      particular, measurement of the kinetics of the NOE, often facilitated by
      selective 1D NOE buildup experiments, can generate invaluable quantitative
      distance information for the molecule being investigated. In practice, analysis
      of such kinetic NOE data routinely assumes a first-order approximation of the
      initial buildup rate. However, often times such an approximation holds true only
      for the shortest mixing times. As shown by Macura and others, the linear range of
      the NOE buildup obtained from 2D NOESY and exchange experiments can be
      substantially extended by simply scaling the NOE cross-peaks against the
      corresponding diagonal peaks. In this note, we demonstrate through a detailed
      analysis that the same approach can be applied to the analysis of 1D NOE data
      obtained with the DPFGSE NOE pulse sequence, one of the most widely used
      selective 1D NOE experiments today. We show that this approach allows the
      inclusion of data points acquired with much longer mixing times in the analysis
      and thus considerably improves the accuracy of the measured cross-relaxation
      rates and internuclear distances, while considerably simplifying the data
      analysis. Similar results can be obtained for the rotating frame DPFGSE ROE
      experiment.

PMID- 16807014
TI  - Characteristics of sensory DRG neurons innervating the wrist joint in rats.
AB  - BACKGROUND: Wrist pain can be the result of trauma, or inflammatory processes
      such as arthritis or synovitis. There is evidence that sensory nerve fibers are
      present in the wrist joints of animals and humans; however, the sensory
      innervation pattern of the wrist, as well as the types of nerves innervating it,
      have not been clarified. The purpose of this study was to characterize the types
      of sensory dorsal root ganglion (DRG) neurons innervating the wrist joint in the
      rat. METHODS: In this study, retrograde neurotransport was combined with lectin
      affinity histochemistry and immunohistochemistry to characterize DRG neurons
      innervating the wrist joint in rats. We used 3 markers: calcitonin gene-related
      peptide (CGRP) as a marker of small, peptide-containing neurons associated with
      inflammatory pain; the glycoprotein binding the isolectin from Griffonia
      simplicifolia (IB4) for small, non-peptide-containing neurons related to
      transmission of pain following nerve injury; and neurofilament 200 (NF200) for
      small and large myelinated fibers. IB4-binding and CGRP-containing neurons are
      typically involved in pain sensation, whereas NF200 is associated with pain and
      proprioception. RESULTS: Neurons innervating the wrist joints, retrogradely
      labeled with fluoro-gold (FG), were distributed throughout DRGs from C6 to T1. Of
      all of the FG labeled neurons, the percentage of NF200 immunoreactive (IR)
      neurons and CGRP-IR neurons were 26% and 45%, respectively. The percentage of IB4
      binding neurons was 3%, significantly less than the ratio of CGRP-IR neurons to
      the total FG labeled neurons. CONCLUSION: Under physiological conditions in rats,
      DRG neurons transmit several types of sensation from the wrist joint including
      proprioception and pain. Most of the labeled neurons were CGRP-IR peptide
      containing neurons. It is likely that these neurons are the predominant afferents
      for inflammatory pain signals from the wrist. Because peptide-containing neurons
      are associated with inflammatory pain, it is likely that the inflammation in the
      wrist joint causes wrist joint pain.

PMID- 16807016
TI  - Gradient shimming with spectrum optimisation.
AB  - Shimming, i.e. homogenising the unavoidable distortion of the static magnetic
      field B0 in NMR spectroscopy, is still an annoying, time consuming task. Although
      compared with conventional manual or computerised search methods gradient
      shimming initiated a new era in terms of operation and efficiency, there remain
      aspects that inhibit fully automated shimming with a result of guaranteed
      quality. The major reason for this limitation is that the judgement of the
      quality of the B0 homogeneity takes place in the spatial domain, although the
      actual objects of interest are the lines in the spectral domain. In this work,
      this restriction is removed by the introduction of a new framework for gradient
      shimming that enables to directly aim at the spectrum quality. Based on the
      mapped B0 field shimming is simulated and spectra are calculated for the virtual
      residual inhomogeneity. Using a suitable criterion to judge the spectrum quality
      an optimisation is performed, thus providing the predicted optimum spectrum and
      the corresponding residual B0 field. This target field is then aimed at during
      the real, iterative shimming procedure. For the widely applicable case of
      optimising the shape of a single line a powerful quality criterion was developed
      using an envelope of the calculated lineshape spectrum. The whole procedure is
      demonstrated for adjusting the on-axis shim functions based on one-dimensional
      field map data and for both on- and off-axis shimming using three-dimensional
      data. The results are verified with 1H NMR spectra acquired on standard NMR test
      samples.

PMID- 16807017
TI  - Spin 3/2 Zeeman perturbed NQR in the presence of slow sample rotation.
AB  - Theoretical and experimental results are presented for the case of Zeeman
      perturbed nuclear quadrupole resonance (NQR) using spin-3/2 nuclei with a small
      Zeeman interaction, gammaB0, while the sample is very slowly rotated. It is found
      that the decay envelope for a simple two-pulse echo measurement can be strongly
      affected even though the sample may rotate only a few degrees or less during the
      course of the measurement. To lowest order the decay envelope can be described
      using a one dimensional function of the product of gammaB0, the rotation rate,
      and the square of the pulse spacing. Aside from an indirect and weak dependence
      on the quadrupole asymmetry parameter, eta, the result is independent of the NQR
      frequency. Identical results are expected for a stationary sample in a small
      rotating magnetic field. The effect seen here may be used to advantage to measure
      rotational motion, for example of particles in fluids, or may be an additional
      complication for some Zeeman perturbed NQR measurements, including some NQR
      detection and imaging methods.

PMID- 16807018
TI  - Selective J-resolved spectra: a double pulsed field gradient spin-echo approach.
AB  - A simple method to obtain selective J-resolved spectra is presented, which relies
      on the refocusing properties of double pulsed field gradient spin-echoes and
      provides unambiguous assignment of the measured coupling constants. The proposed
      examples show how this method is of general applicability, and requires no more
      than a simple optimization strategy to produce artifact-free spectra. Examples of
      application include the determination of a small, long-range coupling constant
      (0.7 Hz) in trans-retinal and Halpha couplings in a tripeptide.

PMID- 16807019
TI  - Indirect detection of nitrogen-14 in solids via protons by nuclear magnetic
      resonance spectroscopy.
AB  - This Communication describes the indirect detection of 14N nuclei (spin I=1) in
      solids by nuclear magnetic resonance (NMR) spectroscopy. The two-dimensional
      correlation method used here is closely related to the heteronuclear multiple
      quantum correlation (HMQC) experiment introduced in 1979 to study molecules in
      liquids, which has recently been used to study solids spinning at the magic
      angle. The difference is that the coherence transfer from neighboring 1H nuclei
      to 14N is achieved via a combination of J couplings and residual dipolar
      splittings (RDS). Projections of the two-dimensional correlation spectra onto the
      14N dimension yield powder patterns which reflect the 14N quadrupolar
      interaction. In contrast to the indirect detection of 14N via 13C nuclei that was
      recently demonstrated [Gan, J. Am. Chem. Soc. 128 (2006) 6040; Cavadini et. al.,
      J. Am. Chem. Soc., 128 (2006) 7706], this approach may benefit from enhanced
      sensitivity, and does not require isotopic enrichment in 13C, although the 1H
      line-widths may have to be reduced upon selective deuteration.

PMID- 16807020
TI  - Spatially encoded pulse sequences for the acquisition of high resolution NMR
      spectra in inhomogeneous fields.
AB  - We have recently proposed a protocol for retrieving nuclear magnetic resonance
      (NMR) spectra based on a spatially-dependent encoding of the MR interactions. It
      has also been shown that the spatial selectivity with which spins are manipulated
      during such encoding opens up new avenues towards the removal of magnetic field
      inhomogeneities; not by demanding extreme Bo field uniformities, but rather by
      compensating for the dephasing effects introduced by the field distribution at a
      radiofrequency excitation and/or refocusing level. The present study discusses in
      further detail a number of strategies deriving from this principle, geared at
      acquiring both uni- as well as multi-dimensional spectroscopic data at high
      resolution conditions. Different variants are presented, tailored according to
      the relative sensitivity and chemical nature of the spin system being explored.
      In particular a simple multi-scan experiment is discussed capable of affording
      substantial improvements in the spectral resolution, at nearly no sensitivity or
      scaling penalties. This new compensation scheme is therefore well-suited for the
      collection of high-resolution data in low-field systems possessing limited signal
      to-noise ratios, where magnetic field heterogeneities might present a serious
      obstacle. Potential areas of applications of these techniques include high-field
      in vivo NMR studies in regions near tissue/air interfaces, clinical low field MR
      spectroscopy on relatively large off-center volumes difficult to shim, and ex
      situ NMR. The principles of the different compensation methods are reviewed and
      experimentally demonstrated for one-dimensional inhomogeneities; further
      improvements and extensions are briefly discussed.

PMID- 16807021
TI  - Diffusion coefficient distribution from NMR-DOSY experiments using Hopfield
      neural network.
AB  - Diffusion ordered spectroscopy (DOSY) is a powerful two-dimensional NMR method to
      study molecular translation in various systems. The diffusion coefficients are
      usually retrieved, at each frequency, from a fit procedure on the experimental
      data, considering a unique coefficient for each molecule or mixture. However, the
      fit can be improved if one regards the decaying curve as a multiexponential
      function and the diffusion coefficient as a distribution. This work presents a
      computer code based on the Hopfield neural network to invert the data. One small
      molecule binary mixture with close diffusion coefficients is treated with this
      approach, demonstrating the effectiveness of the method.

PMID- 16807022
TI  - Functional anatomy of bronchial veins.
AB  - The amount of bronchial arterial blood that drains into the systemic venous
      system is not known. Therefore, in this study we further delineated the
      functional anatomy of the bronchial venous system in six adult, anesthetized, and
      mechanically ventilated sheep. Through a left thoracotomy, the left azygos vein
      was dissected and the insertion of the bronchial vein into the azygos vein was
      identified. A pouch was created by ligating the azygos vein on either side of the
      insertion of the bronchial vein. A catheter was inserted into this pouch for the
      measurement of bronchial venous occlusion pressure and bronchial venous blood
      flow. An ultrasonic flow probe was placed around the common bronchial branch of
      the bronchoesophageal artery to monitor the bronchial arterial blood flow.
      Catheters were also placed into the carotid artery and the pulmonary artery. The
      mean bronchial blood flow was 20.6+/-4.2mlmin(-1) (mean+/-SEM) and, of this, only
      about 13% of the blood flow drained into the azygos vein. The mean systemic
      artery pressure was 72.4+/-4.1mmHg whereas the mean bronchial venous occlusion
      pressure was 38.1+/-2.1mmHg. The mean values for blood gas analysis were as
      follows: bronchial venous blood pH=7.54+/-0.02, PCO(2)=35+/-2.6, PO(2)=95+/
      5.7mmHg; systemic venous blood-pH=7.43+/-0.02, PCO(2)=48+/-3.2, PO(2)=42+/
      2.0mmHg; systemic arterial blood-pH=7.51+/-0.03, PCO(2)=39+/-2.1, PO(2)=169+/
      9.8mmHg. We conclude that the major portion of the bronchial arterial blood flow
      normally drains into the pulmonary circulation and only about 13% drains into the
      bronchial venous system. In addition, the oxygen content of the bronchial venous
      blood is similar to that in the systemic arterial blood.

PMID- 16807023
TI  - Additional clinical benefit of enoxaparin in COPD patients receiving salmeterol
      and fluticasone propionate in combination.
AB  - It is now well recognised that heparin possesses numerous anti-inflammatory
      properties in addition to its anticoagulant properties. Thus, the aim of this
      study was to investigate the effects of the low molecular weight heparin,
      enoxaparin (ENX), as an add-on therapy for a period of 12 weeks, to inhaled
      salmeterol/fluticasone propionate (SLM/FP) combination in patients with stable
      chronic obstructive pulmonary disease (COPD). Forty-six patients were randomised
      to receive 12 weeks of treatment in one of two treatment groups: (1) fixed
      combination of SLM 50 microg and FP 500 microg Diskus, one inhalation twice
      daily; or (2) as group 1 plus 20 mg ENX administered subcutaneously once daily
      for 12 weeks. Patients attended the clinic before and after 4, 8 and 12 weeks of
      treatment for evaluations of lung function, blood gas tensions, dyspnoea and
      supplemental salbutamol use. Thirty-six patients completed the 12-week treatment
      period, 20 from group 1 and 16 from group 2. A significant increase in forced
      expiratory volume in 1 s (FEV1) over baseline was observed after 12 weeks of
      treatment in group 1 (0.145 L, 95% CI: 0.994-1.406, p<0.01), whilst significant
      increases in FEV1 over baseline were observed in group 2 after 4, 8 and 12 weeks
      of treatment with a maximum increase at 12 weeks of 0.244 L (95% CI: 1.175-1.596,
      p<0.01). Both treatment groups experienced similar improvements in blood gas
      tensions, dyspnoea and supplemental salbutamol use. Our results suggest that
      addition of ENX to conventional therapy of COPD may provide additional clinical
      benefit and must be further investigated as a treatment for COPD.

PMID- 16807024
TI  - Effects of hypergravity environments on amphibian development, gene expression
      and apoptosis.
AB  - This study investigates how rearing under conditions of hypergravity affects
      amphibian development, Xotx2 and Xag1 gene expression and apoptosis. Uncleaved
      Xenopus laevis eggs 20 min after insemination, 2 cell stage embryos, and gastrula
      stage embryos were raised at 2G and 5G, while controls were raised in normal
      gravity. Apoptosis in brain and eye inner structures of hatching embryos was
      scored using the TUNEL staining method, and gene expression in tail-bud embryos
      was analyzed by whole-mount in situ hybridization. Results showed that: (1) 5G
      retarded the development of eggs and embryos and induced microcephaly and
      microphthalmia. (2) 5G suppressed the expression of the two genes, Xotx2
      (involved in fore- and midbrain and eye development) and Xag1 (regulating cement
      gland formation). (3) Eggs and 2 cell stage embryos raised at 5G showed a greater
      extent of brain and eye apoptosis compared with controls, while those raised at
      2G showed no significant difference. These findings suggest that high gravity
      suppresses certain gene functions and induces abnormal apoptosis in brain and
      eyes, resulting in developmental retardation and various morphological
      abnormalities.

PMID- 16807025
TI  - An endothelial-cell-enriched primary culture system to study vascular endothelial
      growth factor (VEGF A) expression in a teleost, the Japanese eel (Anguilla
      japonica).
AB  - A partial gene for eel (Anguilla japonica) vascular endothelial growth factor
      (VEGF) has been cloned and an endothelial-cell-enriched primary culture derived
      from rete mirabile established to study regulation of the expression of the eel
      VEGF gene. Cells were cultured in M199 medium containing 0.1% fetal calf serum
      (FCS) and serum-free M199 medium for long-and short-term experiments,
      respectively. Cells were separately treated with cobalt ions (Co2+), basic
      fibroblast growth factor (bFGF), and estradiol (E2), which have been demonstrated
      to stimulate mammalian VEGF A expression, followed by quantification of the VEGF
      mRNA levels by real-time reverse transcription polymerase chain reaction. Our
      results show that: (1) the deduced eel VEGF protein encoded by the cloned gene is
      about 130 amino acids in length, and is closely related to a zebrafish (Danio
      rerio) VEGF A; (2) the endothelial-cell-enriched rete mirabile primary culture
      containing mainly (over 70%) the capillary endothelial cells; (3) the expression
      levels of the eel VEGF transcript were increased by Co2+, bFGF, and E2 treatments
      in a dose-and time-dependent manner. Our data demonstrate that an eel partial
      VEGF gene has been cloned and its regulation of expression in endothelial-cell
      enriched rete mirabile cell culture is similar to that in higher vertebrates.

PMID- 16807026
TI  - The activity of several components of the innate immune system in diploid and
      triploid turbot.
AB  - The use of triploid fish may be of interest in research, e.g. study of how this
      condition affects the size and activity of cells. In addition, triploid fish are
      sterile and production of triploids in fish species that are marketed after
      reaching sexual maturity may be of economic interest. In the present study, the
      effects of triploidy on the activity of several components of the innate immune
      system of turbot (Psetta maxima L) were determined. Triploid turbot had bigger
      cells (erythrocytes and neutrophils) but the number of blood erythrocytes,
      leucocytes and thrombocytes was lower than in diploid fish. The differential cell
      count was similar in both types of fish. The respiratory burst and the phagocytic
      activities were higher in neutrophils of triploid turbot. However, because the
      number of neutrophils was higher in diploids, the total respiratory burst
      activity and the phagocytosis per microliter of blood was similar in both types
      of fish. No differences were found in serum complement, lysozyme or bactericidal
      activities. The results indicate that the activities of the humoral components of
      the innate immune system tested are similar in diploid and triploid fish and that
      the lower leucocyte number found in triploids is compensated for by higher cell
      activity.

PMID- 16807027
TI  - Rapid metabolic adaptation in European sea bass (Dicentrarchus labrax) juveniles
      fed different carbohydrate sources after heat shock stress.
AB  - A study was conducted to evaluate the effect of two dietary carbohydrate sources
      (waxy maize starch and glucose) on the metabolic adaptation of sea bass juveniles
      (initial weight: 24 g) to a heat shock treatment (temperature rise from 18
      degrees C to 25 degrees C within 24 h). Two isonitrogenous and isolipidic diets
      were formulated to contain 20% waxy maize starch (WS diet) or 20% glucose (GLU
      diet). Triplicate groups of fish were fed to near satiation for 4 weeks at both
      temperatures (18 degrees C and 25 degrees C). Then, fish previously maintained at
      18 degrees C were submitted to a heat shock (18 degrees C to 25 degrees C) and
      continued to be fed with the same diets during 1 more week. The higher water
      temperature significantly improved growth performance, feed efficiency, as well
      as protein efficiency ratio, independently of diet. At 25 degrees C, but not at
      18 degrees C, growth of fish fed the WS diet was higher than that of fish fed the
      GLU diet. Plasma glucose levels were higher in sea bass fed the GLU diet and not
      influenced by water temperature. Fish fed a glucose diet or reared at high
      temperatures (25 degrees C) showed enhanced liver glycolytic, lipogenic and
      gluconeogenic capacities compared to fish fed a starch diet or reared at low
      temperatures (18 degrees C). For the majority of the enzymes studied, 1 week
      seemed to be enough time for metabolic adaptation in sea bass submitted to an
      acute heat shock. Irrespective of carbohydrate source, HSP70 gene expression was
      similar in both cold water (18 degrees C) and warm water (25 degrees C)
      acclimated sea bass. A weak down regulation was observed after heat shock only in
      fish fed the GLU diet. This suggests that HSP70 gene expression is not affected
      by the rearing temperature per se.

PMID- 16807028
TI  - Novel function of the skin in calcium metabolism in female and male chickens
      (Gallus domesticus).
AB  - To study the role of the skin in differential calcium metabolism in White Leghorn
      chickens, we compared the composition of suction blister fluid (SBF) collected
      from cutaneous blisters with blood and serum in female and male animals in
      various physiological states. As an estimate for interstitial fluid (IF), SBF was
      used as a determinant of local cutaneous metabolism. Sample collection was
      carried out under ketamine-xylazine anesthesia. Eight chickens of both sexes were
      raised freely in similar environmental conditions and fed with similar food
      during their growth from juvenile to sexually mature and fully adult state. SBF,
      blood and serum were examined for concentrations of ionized Ca2+, Na+ and K+ with
      ion-selective electrodes (ISEs), and osmolalities by freezing point osmometry. pH
      and total protein content were also assessed. Our results showed that SBF of
      chickens is calcium-poor at the juvenile state and that it draws more Ca2+ in
      adult males than laying females of the same age. Interestingly, Ca2+ accumulation
      was observed also in females after laying had ceased. There was a positive
      correlation between blood and SBF Ca2+ in females but a negative one in males. In
      general, it was found that SBF of chickens was rich in Na+ and K+, was hypertonic
      compared to serum at the juvenile state and had a protein content of 36-47% of
      that in serum. Different from mammals, SBF in adult chickens was alkaline with
      the mean values of 8.7+/-0.14 in females and 8.8+/-0.06 in males. Age- and sex
      related variability in cutaneous Ca2+ concentrations in chickens, and the
      differences of SBF composition between that of mammals point to a novel role of
      skin functions in avians. Possible functions of the skin as a dynamic calcium
      source balancing the free circulating Ca2+ levels and, also, as an excretory
      organ for Ca2+ are discussed.

PMID- 16807029
TI  - Stress protein response in two sibling species of Marenzelleria (Polychaeta:
      Spionidae): is there an influence of acclimation salinity?
AB  - The induction and synthesis of stress proteins in the polychaete sibling species
      Marenzelleria viridis and M. neglecta was investigated at two different
      acclimation salinities (10 and 25 ppt). By in vitro labeling of dissected
      metameres with (35)S-methionine/cysteine and electrophoretic separation, four
      size classes of heat shock proteins (Hsps) were detected corresponding to 86, 78,
      75 and 27 kDa. All Hsps, with the exception of Hsp86, represent a complex of
      multiple isoforms. The sibling species differed in three aspects of their heat
      shock response: (1) the induction temperature for Hsp75 synthesis was 25 degrees
      C and 30 degrees C in M. viridis and M. neglecta, respectively; (2) the relative
      level of synthesis of Hsp75 was higher in M. viridis; (3) the heat shock response
      was inactivated at a higher temperature in M. neglecta compared to M. viridis.
      The results showed that acclimation salinity had no explicit effect on Hsp
      synthesis in either species and that M. viridis was thermally more sensitive than
      its sibling species. We proposed that temperature, alone or in combination with
      other abiotic factors, plays a far greater role in the biogeographic distribution
      in Marenzelleria spp. than has been estimated so far.

PMID- 16807030
TI  - Pronase digestion of brush border membrane-bound Cry1Aa shows that almost the
      whole activated Cry1Aa molecule penetrates into the membrane.
AB  - Bacillus thuringiensis insecticidal proteins, Cry toxins, following ingestion by
      insect larvae, induce insecticidal effect by penetrating the brush border
      membranes (BBM) of midgut epithelial cells. Purified, activated B. thuringiensis
      Cry1Aa bound to Bombyx mori BBMV or unbound Cry1Aa were vigorously digested with
      Pronase. Both digests were compared by Western blotting. Free Cry1Aa was digested
      to alpha-helix and/or to amino acids at 1 mg Pronase/mL within 2.4 h at 37
      degrees C. Whereas, BBMV-bound Cry1Aa was very resistant to Pronase digestion and
      even at 2 mg for 24 h, 7.5 kDa and approximately 30 kDa peptide were detected by
      alpha-2,3 antiserum, and alpha-4,5 and alpha-6,7 antisera, respectively. Another
      approximately 30 kDa peptide was also detected by beta-6-11 and domain III
      antisera. These fragments are believed either to be embedded in or to strongly
      interact with the BBMV. The 7.5 and former approximately 30 kDa peptides are
      thought to be derived from alpha-2,3 helix and stretch of alpha-4 to alpha-7
      helices. Furthermore the latter approximately 30 kDa was thought to include the
      stretch of beta-6 to domain III. Moreover, the embedded Cry1Aa molecule appears
      to be segregated in some areas of beta-1-5 sheets, resulting in the above two
      approximately 30 kDa peptides. From these digestion patterns, we proposed new
      membrane insertion model for single Cry1Aa molecule. On the other hand, in
      digestion of BBMV-bound Cry1Aa, 15 kDa peptide which was recognized only by alpha
      4,5 antiserum was observed. This fragment must be dimeric alpha-4,5 helices and
      we discussed the origin of this peptide.

PMID- 16807031
TI  - Molecular characterization of the sarcoplasmic calcium-binding protein (SCP) from
      crayfish Procambarus clarkii.
AB  - Sarcoplasmic Calcium-binding Protein (SCP) is believed to function as the
      invertebrate equivalent of vertebrate parvalbumin, namely to "buffer" cytosolic
      Ca2+. We have cloned and characterized a novel SCP from axial abdominal muscle of
      crayfish Procambarus clarkii (referred to as pcSCP1), and have examined tissue
      specific distribution and expression as a function of molting stage in non
      epithelial and epithelial tissues. The complete sequence of pcSCP1 consists of
      1,052 bp with a 579 bp open reading frame, coding for 193 amino acid residues
      (molecular mass of 21.8 kDa). There is a 387 bp 3' terminal non-coding region
      with a poly (A) tail. The deduced pcSCP1 protein sequence matched most closely
      with published SCP sequences from another crayfish Astacus leptodactylus (92.8%)
      and from shrimp (78.6-81.2%) and fruit fly (53%). Real-time PCR analysis
      confirmed that pcSCP1 is ubiquitously expressed in all tissues tested (gill,
      hepatopancreas, intestine, antennal gland, muscle); however it is most abundant
      in muscle particularly in the axial abdominal muscle. The real-time PCR analysis
      revealed that pcSCP1 expression is downregulated in pre- and postmolt stages
      compared with intermolt. Epithelial (hepatopancreas and antennal gland) SCP
      expression exhibited a more dramatic decrease than that observed in muscle.
      Expression trends for pcSCP1 paralleled published trends for sarco/endoplasmic
      reticular calcium ATPase (SERCA), suggesting that their cellular function in
      regulating intracellular Ca2+ is linked.

PMID- 16807032
TI  - Generating short-term kinetic responses of primary metabolism of Penicillium
      chrysogenum through glucose perturbation in the bioscope mini reactor.
AB  - A first study of the in vivo kinetic properties of primary metabolism of
      Penicillium chrysogenum is presented. Dynamic metabolite data have been generated
      by rapidly increasing the extracellular glucose concentration of cells cultivated
      under well-defined conditions in an aerobic glucose-limited chemostat followed by
      measurement of the fast dynamic response of the primary metabolite levels
      (glucose pulse experiment). These experiments were carried out directly in the
      chemostat as well as in a mini plug flow reactor (BioScope) outside the
      chemostat. The results of the glucose pulse experiments carried out in the
      chemostat and the Bioscope were highly similar. During the 90 s time window of
      the pulse experiment, the glucose consumption rate increased to a value twice as
      high as in the steady state, a much lower increase than observed for the
      fermenting yeast Saccharomyces cerevisiae under similar conditions. Although the
      observed metabolite patterns in P. chrysogenum were comparable to S. cerevisiae
      large differences in the magnitude of the dynamic behavior were observed between
      both organisms. During the pulse experiment the level of glycolytic and TCA cycle
      intermediates, and adenine nucleotides changed between two- and five-fold.
      Furthermore, a highly similar five-fold increase in the cytocolic NADH/NAD ratio
      could be calculated from two independent equilibrium assumptions (fructose 1,6
      bis-phosphate to the pool of 2 and 3PG and oxaloacetate to fumarate with
      glutamate transaminase). It was also found that the C4 pool (aspartate, fumarate,
      and malate) became much more reduced due to this increase in NADH/NAD ratio.
      Equilibrium conditions were confirmed to exist in the hexose-P pool, the
      glycolysis between F16bP and 2+3PG and in the C4 pool of the TCA cycle (fumarate,
      malate, oxaloacetate and aspartate).

PMID- 16807033
TI  - Enzyme replacement therapy in alpha-mannosidosis guinea-pigs.
AB  - alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity
      of lysosomal alpha-mannosidase and is characterised by massive accumulation of
      mannose-containing oligosaccharides in affected individuals. Patients develop
      behaviour and learning difficulties, skeletal abnormalities, immune deficiency
      and hearing impairment. Disease in alpha-mannosidosis guinea-pigs resembles the
      clinical, histopathological, biochemical and molecular features of the human
      disease. We have used the guinea-pig model to investigate efficacy of enzyme
      replacement therapy as a treatment for alpha-mannosidosis. Intravenous
      recombinant human lysosomal alpha-mannosidase, administered at a dose of 1mg/kg,
      was cleared from circulation with a half-life of 53 h, with significant enzyme
      activity (1.4x normal levels) detected in circulation one week post-injection.
      alpha-Mannosidase administered to alpha-mannosidosis guinea-pigs at 1mg/kg (onset
      at birth or approximately 30 days) and 10mg/kg (at birth) was distributed widely
      amongst tissues, including to capillary depleted brain. By monitoring with tandem
      mass spectrometry, enzyme replacement therapy was found to be effective in
      reducing stored substrates in peripheral tissues at both dose rates, and in brain
      by up to 39% at the 10mg/kg dose, compared with untreated alpha-mannosidosis
      controls. Reductions of up to 60% of urinary mannose containing oligosaccharides
      were also observed. No histological improvements were seen in the brain at either
      dose, however marked decreases in lysosomal vacuolation in liver, kidney, spleen
      and endocrine pancreas, as well as a significant reduction in trigeminal ganglion
      neurons were observed. Multiple injections of 1mg/kg recombinant enzyme in alpha
      mannosidosis guinea-pigs induced a very rapid humoral immune response precluding
      long-term intravenous treatment.

PMID- 16807034
TI  - Sexually transmitted Chlamydia trachomatis, Neisseria gonorrhoeae, and HIV-1
      infections in two at-risk populations in Barcelona: female street prostitutes and
      STI clinic attendees.
AB  - OBJECTIVE: To determine the prevalence of Chlamydia trachomatis (CT), Neisseria
      gonorrhoeae (NG), and HIV-1 infections in female street prostitutes and STI
      clinic attendees in Barcelona. DESIGN: This was a prospective study carried out
      in two four-month periods over two years. Urine specimens were tested for CT and
      NG using a PCR pooling algorithm. Among street prostitutes HIV-1 testing in urine
      was also carried out. RESULTS: The prevalences of CT, NG, and HIV-1 in female
      street prostitutes (n=301) were 4.7%, 3.7%, and 1.0%, respectively. Women from
      Eastern Europe had the highest prevalence of CT (p=0.01). Prevalences of CT, NG,
      and HIV-1 among all clinic attendees (n=536) were 4.3%, 4.5%, and 4.4%,
      respectively. Prevalence of HIV-1 infection among homosexual men was higher
      compared with heterosexual men and women (p<0.001). CONCLUSIONS: Overall CT
      prevalence is currently lower than in other European countries, although it could
      increase as a result of immigration. Rates of HIV-1 and of NG are higher among
      homosexual than among heterosexual men.

PMID- 16807035
TI  - [Metastatic nasopharyngeal carcinoma: clinical study and therapeutic results of
      95 cases].
AB  - PURPOSE: The objective of this retrospective study was to discuss the
      epidemioclinical criteria and the therapeutic results of metastatic
      nasopharyngeal carcinoma. PATIENTS AND METHODS: The current study concerned 95
      patients with histologically proven nasopharyngeal carcinoma who were metastatic
      at diagnosis or who had developed late metastasis. We reviewed the
      epidemioclinical records of all the patients. Patients were treated with
      chemotherapy (BEC regimen: bleomycin, epirubicin and cisplatin or PBF regimen:
      bleomycin, 5-fluorouacil and cisplatin) and radiotherapy of pauci metastatic
      localizations (single or double) or bone metastasis with high risk of compression
      or fracture+/-associated with locoregional radiotherapy for patients who were
      metastatic at diagnosis. Response was assessed according to the WHO criteria.
      Overall survival was calculated according to the Kaplan-Meier method. A long-term
      disease-free survival was defined from 36 months. RESULTS: There were 34 patients
      who were metastatic at diagnosis and 61 patients who had developed late
      metastasis. The mean age was 41.5 years (sex-ratio: 3.1). Bone metastases were
      the most frequent (83%). Objective and complete response rates were respectively
      75% and 70%, and 32% and 16% for BEC and PBF regimens. Twenty-five patients
      received radiotherapy for pauci metastatic localizations, among whom 19 patients
      who were metastatic at diagnosis received locoregional irradiation. The overall
      survival probability was of 15% for three years. Eleven patients were long
      survivors (extremes: 36 and 134 months). CONCLUSION: Therapeutic results were
      comparable to those reported in other series using platin combination
      chemotherapy. Radiotherapy of metastasis yielded to long-term survival.

PMID- 16807036
TI  - Flagellin in combination with curli fimbriae elicits an immune response in the
      gastrointestinal epithelial cell line HT-29.
AB  - Flagellin is the major cytokine-releasing factor when Salmonella enterica serovar
      Typhimurium (S. Typhimurium) infects intestinal epithelial cells. In this work it
      is shown that curli, an adhesive proteinaceous surface component of
      Enterobacteriaceae involved in biofilm formation of S. Typhimurium and
      Escherichia coli strains can bind flagellin and thus elicit an immune response by
      the intestinal epithelial cell line HT-29.

PMID- 16807037
TI  - Development of a rapid and convenient method for the quantification of HIV-1
      budding.
AB  - In cells, the expression of Gag protein, one of the major structural proteins of
      retroviruses, is sufficient for budding virus-like particles (VLPs) from the cell
      surface. We have previously reported that spheroplasts of Saccharomyces
      cerevisiae expressing HIV-1 Gag proteins from an episomal plasmid constitutively
      released a large amount of VLPs into culture media; however, commercially
      available ELISA kits which detect mature capsid of HIV-1 could not detect
      uncleaved 55-kDa Gag proteins released from budding yeast. We therefore developed
      a method to quantitate VLP levels released from budding yeast by using fusion
      protein from HIV-1 Gag and Firefly Luciferase. This system is useful for
      screening cellular factor(s) involved in retrovirus budding from S. cerevisiae.

PMID- 16807038
TI  - Are the increases in local tumour necrosis factor and lipid peroxidation observed
      in pre-starved mice infected with Salmonella typhimurium markers of increased
      liver damage?
AB  - Pathogenic microorganisms are known to sense and process signals within their
      hosts, including those resulting from starvation. Therefore, an attempt was made
      to evaluate the extent and the possible underlying mechanism of Salmonella
      typhimurium-induced hepatic damage using pre-starved laboratory mice. The
      following parameters were analysed, comparing control, fed infected, starved, and
      starved infected mice: the bacterial load in the liver, fluctuations in liver
      derived enzymes alanine-aminotransferase and aspartate-aminotransferase,
      histopathological changes, lipid peroxidation as well as estimation of reduced
      glutathione, superoxide dismutase and catalase, along with the TNF content in
      livers. The number of bacterial cells recovered from starved infected livers at 3
      days post-S. typhimurium inoculation was comparable to the number recovered from
      fed infected livers at 5 days post-Salmonella inoculation, indicating an early
      increase in the development of the bacteria in starved mice. A marked elevation
      in liver-derived enzymes in mouse serum and significant histopathological changes
      are markers of liver damage of higher amplitude in starved infected mice.
      Analysis of the liver indicated a significant increase in lipid peroxidation in
      starved infected mice compared to their control counterparts, a process coupled
      with increased TNF level. Although the reduced glutathione levels showed a marked
      increase in the starved infected mice, there was a significant decrease in
      superoxide dismutase and catalase activities in this group.

PMID- 16807039
TI  - Purification of outer membrane vesicles from Pseudomonas aeruginosa and their
      activation of an IL-8 response.
AB  - Considerable lung injury results from the inflammatory response to Pseudomonas
      aeruginosa infections in patients with cystic fibrosis (CF). The P. aeruginosa
      laboratory strain PAO1, an environmental isolate, and isolates from CF patients
      were cultured in vitro and outer membrane vesicles from those cultures were
      quantitated, purified, and characterized. Vesicles were produced throughout the
      growth phases of the culture and vesicle yield was strain-independent. Strain
      dependent differences in the protein composition of vesicles were quantitated and
      identified. The aminopeptidase PaAP (PA2939) was highly enriched in vesicles from
      CF isolates. Vesicles from all strains elicited IL-8 secretion by lung epithelial
      cells. These results suggest that P. aeruginosa colonizing the CF lung may
      produce vesicles with a particular composition and that the vesicles could
      contribute to inflammation.

PMID- 16807040
TI  - Group B streptococcal arthritis.
AB  - Recent data suggest that group B streptococcal arthritis is being increasingly
      diagnosed. We retrospectively reviewed the records of patients admitted to our
      Teaching Hospital Rheumatology Department for septic arthritis between May 2000
      and May 2004 and we reviewed the relevant literature to determine the
      characteristics of group B streptococcal arthritis. We compared age, hospital
      stay duration, and number of joints involved in the patients with group B
      streptococcal arthritis and in those with septic arthritis due to other
      organisms. Of 48 consecutive patients with septic arthritis, five (10.4%) had
      arthritis due to group B streptococci. Mean age of these five patients was 51.6+/
      18.3 years and mean hospital stay duration was 13.2+/-9.23 days. Arthritis
      distribution was oligoarticular in three patients, polyarticular in one patient,
      and monoarticular in one patient. The mean number of involved joints was
      significantly (P=0.005) higher in the patients with group B streptococcal
      arthritis than in the other patients (2.6+/-1.5 vs 1.1+/-0.4 joints). Age and
      hospital stay duration were not significantly different. The frequently
      oligoarticular or polyarticular distribution of group B streptococcal arthritis,
      together with the sometimes limited symptoms, may lead to diagnostic wanderings
      or delays.

PMID- 16807041
TI  - Histoplasma capsulatum tenosynovitis in a patient with rheumatoid arthritis
      scleroderma overlap syndrome.

PMID- 16807042
TI  - Kingella kingae septic arthritis with endocarditis in an adult.
AB  - Kingella kingae is part of the nonpathogenic flora normally found in the oral
      cavity and pharynx. Recent reports have established that K. kingae can cause
      invasive infections in pediatric patients. Few cases have been described in
      adults, however. We report a case of K. kingae arthritis of the knee followed by
      endocarditis in a 59-year-old woman. Physicians and microbiologists should be
      alert to the possibility of K. kingae infection. K. kingae is easy to detect
      provided its specific culture requirements are taken into account. Synovial fluid
      inoculation into blood culture vials considerably increases the likelihood of K.
      kingae recovery in patients with septic arthritis.

PMID- 16807043
TI  - Systemic vasculitis revealing a benign tumor: a paraneoplastic syndrome?
AB  - Systemic vasculitis is a rare event in the course of malignant tumors and has not
      been described in association with benign tumors. We report a case of renal
      oncocytoma in a patient who presented with digital necrosis, arthralgia, myalgia,
      and a decline in general health. The symptoms resolved fully after tumor
      excision, supporting a diagnosis of paraneoplastic syndrome.

PMID- 16807044
TI  - [Place of surgery in the management of gestational trophoblastic tumors. Gynecol
      Obstet Fertil 2006;34:233-8].

PMID- 16807045
TI  - [Human papillomavirus prophylactic vaccines: stakes and perspectives].
AB  - Human Papillomavirus (HPV) infection is established as the necessary cause of
      cervical precancers and cancers. To date, more than 120 genotypes are known, but
      only high risk oncogen genotypes could induce a cancer. HPV 16 and 18 are implied
      in nearly 70% of cervical cancer around the world. Although some persistent HPV
      infections progress to cervical cancer, host immunity is generally able to clear
      most HPV infections providing an opportunity for cervical cancer prevention
      through vaccination. Candidate prophylactic vaccines based on papillomavirus L1
      virus-like particles (VLPs) are currently on human clinical trials: one targeting
      cervical cancer with a bivalent VLP L1 vaccine containing the two genotypes most
      frequently involved in cervical cancer (type 16 and 18) and the other, protecting
      against warts as well as cervical cancer, with a quadrivalent HPV VLP L1 vaccine
      containing genotypes 6, 11, 16 and 18. The first clinical trials revealed the
      satisfactory tolerance and excellent immunogenicity of these vaccines inducing
      high serum antibody titers with minimal side effects. After more than three
      years, both clinical trials on women 15 to 25 years old have shown that vaccines
      are able to type specifically protect against nearly 90% of infection and all
      cervical intra-epithelial neoplasia. The vaccinal strategy defined to date
      targets preadolescents and adolescent young females (11-13 years) before the
      first sexual course but some questions are still not resolved concerning the
      prescriber, the actors of the vaccination and the duration of the protection.
      Nevertheless cervical cancer screening should be carried on for many years, even
      if a large vaccinal strategy is decided. Such a vaccine would save lives and
      reduce the need for costly medical procedures and the psychological stress
      induced by this cancer.

PMID- 16807046
TI  - Validation of sensitive human leukocyte antigen-sequence-specific primer and
      probe typing in forensic DNA examination.
AB  - Validation studies were carried out with the commercially available HLA typing
      kit using a PCR-SPP (sequence-specific primer and probe) technique. This
      technique has made it possible to type class I (HLA-A and -B) and class II (HLA
      DRB1 and -DQB1) alleles at low-resolution level with total 10 ng of template DNA,
      in addition to amplify directly from various forms of blood samples without DNA
      isolation procedure. Experimental examinations with bloodstains smeared on cotton
      cloth that were a week to 3 months old, bloodstains on gauze stored for 18 years,
      and buccal cells revealed that this HLA-SPP typing kit is a sensitive and
      reliable method for forensic investigations.

PMID- 16807047
TI  - The forensic availability of a simple and time-saving method for the
      identification of dipteran species to estimate postmortem interval using
      entomological evidence.

PMID- 16807048
TI  - A study on mRNA expressions of fibronectin in dermal and cerebral wound healing
      for wound age estimation.
AB  - We investigated mRNA expressions of fibronectin for wound age estimation during
      dermal and cerebral wound healing. Fibronectin mRNA expressions in the injured
      skin peaked at 8h post-injury. The expressions were detected in endothelial cells
      before and after injury, whereas they were detectable in the epidermal cells at 1
      240 h, in fibroblasts at 1-72 h, in neutrophils and macrophages at 8-72 h,
      respectively. However, the expressions in epidermal cells became relatively weak
      in the subacute phase. Fibronectin mRNA expressions of the injured cerebrum
      increased after the intervention and peaked at 48 h, whereas there was a slight
      decrease during 24h post-injury. Although fibronectin mRNA was seen exclusively
      in the endothelial cells of the intact cerebrum, it was also detected in
      astrocytes during wound healing. From these findings, it was considered that
      fibronectin played an important role in dermal and cerebral wound healing.
      Expression of fibronectin mRNA was considered to indicate the acute phase of
      dermal wound healing, and the subacute phase of cerebral wound healing.

PMID- 16807049
TI  - Synthesis of Pt modified ZSM-5 and beta zeolite catalysts: influence of
      ultrasonic irradiation and preparation methods on physico-chemical and catalytic
      properties in pentane isomerization.
AB  - Influence of preparation methods and ultrasound irradiation on physico-chemical
      and catalytic properties was investigated by synthesizing Pt-ZSM-5 and Pt-Beta
      catalysts by in-situ and impregnation methods and applying ultrasound irradiation
      to synthesis gel mixture of ZSM-5 and Beta zeolites. It was concluded from the X
      ray powder diffraction patterns of Pt-ZSM-5 and Pt-Beta zeolite catalysts that
      introduction of Pt by in-situ method and ultrasound irradiation did not influence
      the structures of ZSM-5 and Beta zeolites. Morphology of ZSM-5 and Beta zeolites
      were investigated by scanning electron microscopy. SEM micrographs showed that
      the Pt-ZSM-5-IS-US catalyst synthesized by in-situ method with ultrasound
      irradiation resulted in smaller crystals of ZSM-5 than Pt-ZSM-5-IS catalyst
      prepared without ultrasound irradiation. Furthermore SEM micrographs of Pt-Beta
      11-IS-US zeolite synthesized using ultrasound irradiation showed much smaller
      crystals than Pt-Beta-11-IM indicating that ultrasound irradiation had a
      significant effect on the morphology of Beta zeolite. Conversion of n-pentane and
      selectivity to iso-pentane over the Pt-ZSM-5-IS-US zeolite catalysts prepared by
      ultrasound irradiation during in-situ introduction of platinum was higher than
      the catalysts prepared without the ultrasound irradiation. Furthermore ultrasound
      irradiated and in-situ synthesized Pt-Beta-11-IS-US catalyst also showed higher
      selectivity to iso-pentane than Pt-H-Beta-11-IM prepared by impregnation method.

PMID- 16807051
TI  - Heart rate variability in mental stress aloud.
AB  - Previous investigations on arithmetic stress with verbalization showed that
      spectral measures of heart rate variability (HRV) did not assess changes in
      autonomic modulation, although the heart rate (HR) increased. In this study non
      linear measures of HRV are determined and linear measures are re-examined in
      order to understand this apparent discrepancy between HR and HRV changes. In 23
      healthy subjects 5-min electrocardiograms (ECGs) were recorded at rest and during
      arithmetic stress aloud. We determined non-linear (short-term scaling exponent,
      sensitivity to the initial condition and signal complexity) and linear (low
      frequency and high-frequency spectral powers) measures. Our results showed that
      averaging concealed out an opposite effect of mental stress aloud on spectral
      measures and that this could be the main reason why the effect was not
      quantified. We found that increase of HR upon mental stress aloud could be
      achieved through the decreased as well as increased modulation in high-frequency
      band (HF). We also showed that non-linear measures distinguished this opposite
      effect of mental stress aloud on linear measures. Decreased HF power is
      associated with increase in short-term scaling exponent and decrease in signal
      complexity, while increased HF power increased sensitivity to the initial
      conditions. Apart from their opposite response to the mental stress, the two
      groups differed in baseline in sensitivity to the initial conditions. We suggest
      that variety of changes in HR dynamics upon different perturbation could be due
      to some differences in intrinsic properties of the system.

PMID- 16807050
TI  - Electrochemistry of nanoscale DNA surface films on carbon.
AB  - A DNA electrochemical biosensor is an integrated receptor-transducer device. The
      most important step in the development and manufacture of a sensitive DNA
      biosensor for the detection of DNA-drug interactions is the immobilization
      procedure of the nucleic acid probe on the transducer surface. Magnetic A/C Mode
      atomic force microscopy (MAC Mode AFM) images in air were used to characterize
      two different procedures for immobilising nanoscale double-stranded DNA (dsDNA)
      surface films on carbon electrodes. Thin film dsDNA layers presented holes in the
      dsDNA film that left parts of the electrode surface uncovered while thicker films
      showed a uniform and complete coverage of the electrode. These two procedures for
      preparing dsDNA-biosensors were used to study the influence of reactive oxygen
      species (ROS) in the mechanism of DNA damage by quercetin, a flavonoid, and
      adriamycin, an anthracycline anticancer drug. The study of quercetin-DNA
      interactions in the presence of Cu(II) ions indicated that the formation of a
      quercetin-Cu(II) complex leads to the formation of ROS necessary to react with
      DNA, disrupting the helix and causing the formation of 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodGuo). Reduced adriamycin radicals are able to directly
      cause oxidative damage to DNA, generating 8-oxodGuo and ROS are not directly
      involved in this genomic mutagenic lesion.

PMID- 16807052
TI  - Electrochemical screening of self-assembling beta-sheet peptides using supported
      phospholipid monolayers.
AB  - In the context of the medical applications of beta-sheet self-assembling
      peptides, it is important to be able to predict their activity at the biological
      membrane level. A study of the interaction of four systematically varied 11
      residue (P11-1, P11-2, P11-6 and P11-7) and one 13-residue (P13-1) designed beta
      sheet self-assembling peptides with DOPC monolayers on a mercury electrode is
      reported in this paper. Experiments were carried out in 0.1 mol dm(-3) KCl
      electrolyte with added phosphate buffer (0.001 mol dm(-3)) at pH approximately
      7.6. The capacity-potential curves of the coated electrode in the presence and
      absence of the different peptides were measured using out-of-phase ac
      voltammetry. The frequency dependence of the complex impedance of the coated
      electrode surfaces in the presence and absence of the peptides was estimated
      between 65,000 and 0.1 Hz at -0.4V versus Ag/AgCl 3.5 mol(-3) dm(-3) KCl. The
      monolayer permeabilising properties of the peptides were studied by following the
      reduction of Tl(I) to Tl(Hg) at the coated electrode. Of the five peptides
      studied, P11-2, P11-7 and P13-1 interact most strongly with the DOPC layer. P11-1
      which has a polar primary structure shows no obvious interaction with the
      phospholipid but surprisingly, it permeabilises the phospholipid layer to Tl(+).

PMID- 16807053
TI  - Rapid screening test for sleep apnea using a nonlinear and nonstationary signal
      processing technique.
AB  - It is hypothesized that obstructive sleep apnea (OSA) can be detected from a
      short-time, daytime recording of the nasal airway pressure, resulting in a
      screening tool to identify adult patients at risk for OSA. A nonlinear and
      nonstationary signal analysis technique based on the Hilbert-Huang transform was
      used to extract signals intrinsic to OSA, using the first two intrinsic mode
      functions from the empirical mode decomposition. The Hilbert spectrum was
      centered around 1.5Hz for normal subjects and shifted upward in frequency scale
      with increased likelihood of OSA. The histogram of the 1.5Hz signal from the
      Hilbert spectrum was used to compute the apnea percentage for assessing OSA. The
      proposed method was tested with two data sets. Data set 1 consisted of 18 human
      subjects with 3 OSA cases from retrospective diagnosis. Data set 2 consisted of
      16 subjects who went through a prospective study of the all-night
      polysomnographic test and the 5-min nasal airway pressure test. The proposed OSA
      detection method achieved 100% sensitivity and 100% specificity for data set 1,
      85.7% sensitivity and 100% specificity for data set 2. While further tests will
      be needed to insure robustness and standardize the instrumentation, the study has
      demonstrated the feasibility of a rapid screening test for obstructive sleep
      apnea.

PMID- 16807054
TI  - Fuzzy support vector machines for adaptive Morse code recognition.
AB  - Morse code is now being harnessed for use in rehabilitation applications of
      augmentative-alternative communication and assistive technology, facilitating
      mobility, environmental control and adapted worksite access. In this paper, Morse
      code is selected as a communication adaptive device for persons who suffer from
      muscle atrophy, cerebral palsy or other severe handicaps. A stable typing rate is
      strictly required for Morse code to be effective as a communication tool.
      Therefore, an adaptive automatic recognition method with a high recognition rate
      is needed. The proposed system uses both fuzzy support vector machines and the
      variable-degree variable-step-size least-mean-square algorithm to achieve these
      objectives. We apply fuzzy memberships to each point, and provide different
      contributions to the decision learning function for support vector machines.
      Statistical analyses demonstrated that the proposed method elicited a higher
      recognition rate than other algorithms in the literature.

PMID- 16807055
TI  - Herpes simplex keratitis.
AB  - Herpes simplex keratitis (HSK) results from an infection with the herpes simplex
      virus type 1 (HSV-1) also known as human herpesvirus type 1 (HHV-1). Primary
      infection may involve an ocular or non-ocular site, following which latency might
      be established principally in the trigeminal ganglion but also in the cornea.
      During latency, the virus appears as a circular episome associated with histones
      with active transcription only from the region encoding the latency-associated
      transcript (LAT). The LAT region is implicated in neuronal survival, anti
      apoptosis, virulence, suppression of transcription, establishment of and
      reactivation from latency. The initial keratitis may develop after infection
      through the "front door route" (entry into the ocular surface from droplet
      spread) or "back door route" (spread to the eye from a non-ocular site,
      principally the mouth). The initial ocular infection may be mild. Visual
      morbidity results from recurrent keratitis, which leads to corneal scarring,
      thinning and neovascularisation. Although, recurrent disease may potentially
      occur through anterograde axonal spread from the trigeminal ganglion to the
      cornea, recent evidence suggests that HSV-1 in the cornea may be another source
      of recurrent disease. The pathogenesis and severity of HSK is largely determined
      by an interaction between viral genes encoded by the strain of HSV-1 and the make
      up of the host's immune system. Herpetic stromal disease is due to the immune
      response to virus within the cornea and the ability of the strain to cause
      corneal stromal disease is correlated with its ability to induce corneal
      vascularisation. The pathogenesis of corneal scarring and vascularisation is
      uncertain but appears to be a complex interaction of various cytokines,
      chemokines and growth factors either brought in by inflammatory cells or produced
      locally in response to HSV-1 infection. Evidence now suggests that HSV-1
      infection disrupts the normal equilibrium between angiogenic and anti-angiogenic
      stimuli leading to vascularisation. Thrombospondin 1 and 2, matricellular
      proteins, involved in wound healing are potent anti-angiogenic factors and appear
      to be one of the key players. Elucidating their roles in corneal scarring and
      vascularisation may lead to improved therapies for HSK.

PMID- 16807056
TI  - Botulinum toxin B ultrasound-guided injections for sialorrhea in amyotrophic
      lateral sclerosis and Parkinson's disease.
AB  - Sialorrhea is frequent and invalidating in patients with amyotrophic lateral
      sclerosis (ALS) or Parkinson's disease (PD). Botulinum toxin (BTX) emerged as an
      alternative to traditional treatments. We evaluated efficacy and tolerability of
      ultrasound-guided BTX-B injections in parotids and submandibular glands in 18
      patients with ALS or PD. At 1 week, both objective (cotton rolls weight) and
      subjective evaluations (dedicated clinical scales) documented sialorrhea
      reduction (p<0.01). ALS patients reported shorter benefit duration (p<0.001) and
      higher prevalence of viscous saliva (seven vs one patients), possibly due to
      different pattern of autonomic involvement. BTX-B seems efficacious in reducing
      sialorrhea in ALS and PD but the risk-benefit ratio might differ between these
      two conditions. This might have implications for clinical practice.

PMID- 16807057
TI  - Schwann cells: origins and role in axonal maintenance and regeneration.
AB  - The Schwann cell plays a vital role in maintaining the peripheral nervous system
      (PNS). Schwann cells are derived from neural crest cells, and come in two types
      either myelinating or non-myelinating Schwann cells. Both play a pivotal role in
      the maintenance and regeneration of axons of the neurons in the PNS. The
      regulation of Schwann cells is mediated a number of different neurotrophic
      factors which signal to transcription factors such as Krox-20, Oct-6 and Sox-10.
      Schwann cells are affected in a number of demyelinating disorders, such as
      Charcot-Marie-Tooth disease and Guillain-Barre Syndrome, infected by
      Mycobacterium leprae to cause leprosy and are responsible for the tumors seen in
      patients with neurofibromatosis type 1 and neurofibromatosis type 2. The Schwann
      cell is under investigation as a therapeutic agent for demyelinating diseases and
      spinal cord injuries. Further research on Schwann cells will help understand
      these diseases and perhaps lead to new treatments.

PMID- 16807058
TI  - Undecanesulfonate does not allosterically activate H+ uniport mediated by
      uncoupling protein-1 in brown adipose tissue mitochondria.
AB  - Undecanesulfonate is transported by uncoupling protein-1. Its inability to induce
      H+ uniport with reconstituted uncoupling protein-1 supports fatty acid cycling
      hypothesis. Rial et al. [Rial, E., Aguirregoitia, E., Jimenez-Jimenez, J., &
      Ledesma, A. (2004). Alkylsulfonates activate the uncoupling protein UCP1:
      Implications for the transport mechanism. Biochimica et Biophysica Acta, 1608,
      122-130], have challenged the fatty acid cycling by observing uncoupling of brown
      adipose tissue mitochondria due to undecanesulfonate, interpreted as allosteric
      activation of uncoupling protein-1. We have estimated undecanesulfonate effects
      after elimination of endogenous fatty acids by carnitine cycle in the presence or
      absence of bovine serum albumin. We show that the undecanesulfonate effect is
      partly due to fatty acid release from albumin when undecanesulfonate releases
      bound fatty acid and partly represents a non-specific uncoupling protein
      independent acceleration of respiration, since it proceeds also in rat heart
      mitochondria lacking uncoupling protein-1 and membrane potential is not decreased
      upon addition of undecanesulfonate without albumin. When the net fatty acid
      induced uncoupling was assayed, the addition of undecanesulfonate even slightly
      inhibited the uncoupled respiration. We conclude that undecanesulfonate does not
      allosterically activate uncoupling protein-1 and that fatty acid cycling cannot
      be excluded on a basis of its non-specific effects.

PMID- 16807059
TI  - Human thyroid carcinoma cell invasion is controlled by the low density
      lipoprotein receptor-related protein-mediated clearance of urokinase plasminogen
      activator.
AB  - The low density lipoprotein receptor-related protein (LRP), a large scavenger
      receptor reported to mediate the uptake and degradation of various ligands,
      emerges as a promising receptor for targeting the invasive behaviour of human
      cancer cells. However, the accurate function of LRP during tumor invasion seems
      to be highly dependent on cellular context and remains controversial. The
      expression patterns of both this receptor and the main proteolytic systems
      involved in cell invasion were examined in two follicular thyroid carcinoma cell
      lines exhibiting different invasive phenotypes. We established that a low
      expression of LRP at the cell surface was associated to elevated extracellular
      MMP2 and urokinase plasminogen activator (uPA) activities as well as to high
      invasiveness properties. Surprisingly, neither exogenously added receptor
      associated protein, an antagonist of LRP, nor LRP blocking antibodies
      significantly modified the amount of extracellular MMP2. Furthermore, the
      invasive phenotype of thyroid carcinoma cells was not related to their matrix
      metalloproteinases amount since different specific inhibitors of these proteases
      failed to affect the invasive properties of both cell lines. Additionally,
      blocking LRP-mediated clearance led to a further increase of the uPA amount and
      activities and to increased invasiveness in both cell lines. Finally thyroid
      carcinoma cells aggressiveness was widely increased by exogenous uPA; and anti
      uPA antibodies treatments abolished both basal and receptor-associated protein
      induced thyroid cell invasion. Overall our results identified the LRP-mediated
      clearance of uPA as one of the mechanisms involved during the control of human
      thyroid carcinoma cell invasion.

PMID- 16807060
TI  - The role of G-CSF in adaptive immunity.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a pleiotropic cytokine playing a
      major role as regulator of hematopoiesis and innate immune responses. There is
      growing evidence that G-CSF also exerts profound immunoregulatory effects in
      adaptive immunity. G-CSF mediates anti-inflammatory reactions accompanied by TH2
      cell differentiation and promotes tolerogeneic cell populations at both poles of
      APC/T cell interaction. These recent findings have highlighted the novel impact
      of G-CSF in transplantation tolerance and autoimmunity. G-CSF represents a
      powerful and promising cytokine to promote T cell tolerance in pathological
      conditions associated with a TH1/TH2 imbalance.

PMID- 16807061
TI  - FiRe and microarrays: a fast answer to burning questions.
AB  - FiRe is a user-friendly Excel macro designed to survey microarray data rapidly.
      This software interactively assembles data from different experiments and
      produces lists of candidate genes according to patterns of gene expression.
      Furthermore, macros bundled with FiRe can compare lists of genes, merge
      information from different spreadsheets, link candidates to information available
      from web-based databases, and produce heat-maps for easy visualization of
      microarray data. FiRe is freely available at
      http://www.unifr.ch/plantbio/FiRe/main.html .

PMID- 16807062
TI  - Pulmonary fissure segmentation on CT.
AB  - A pulmonary fissure is a boundary between the lobes in the lungs. Its
      segmentation is of clinical interest as it facilitates the assessment of lung
      disease on a lobar level. This paper describes a new approach for segmenting the
      major fissures in both lungs on thin-section computed tomography (CT). An image
      transformation called "ridge map" is proposed for enhancing the appearance of
      fissures on CT. A curve-growing process, modeled by a Bayesian network, is
      described that is influenced by both the features of the ridge map and prior
      knowledge of the shape of the fissure. The process is implemented in an adaptive
      regularization framework that balances these influences and reflects the causal
      dependencies in the Bayesian network using an entropy measure. The method
      effectively alleviates the problem of inappropriate weights of regularization
      terms, an effect that can occur with static regularization methods. The method
      was applied to segment and visualize the lobes of the lungs on chest CT of 10
      patients with pulmonary nodules. Only 78 out of 3286 left or right lung regions
      with fissures (2.4%) required manual correction. The average distance between the
      automatically segmented and the manually delineated "ground-truth" fissures was
      1.01 mm, which was similar to the average distance of 1.03 mm between two sets of
      manually segmented fissures. The method has a linear-time worst-case complexity
      and segments the upper lung from the lower lung on a standard computer in less
      than 5 min.

PMID- 16807063
TI  - Bayesian decision theory in sensorimotor control.
AB  - Action selection is a fundamental decision process for us, and depends on the
      state of both our body and the environment. Because signals in our sensory and
      motor systems are corrupted by variability or noise, the nervous system needs to
      estimate these states. To select an optimal action these state estimates need to
      be combined with knowledge of the potential costs or rewards of different action
      outcomes. We review recent studies that have investigated the mechanisms used by
      the nervous system to solve such estimation and decision problems, which show
      that human behaviour is close to that predicted by Bayesian Decision Theory. This
      theory defines optimal behaviour in a world characterized by uncertainty, and
      provides a coherent way of describing sensorimotor processes.

PMID- 16807064
TI  - Probabilistic models of cognition: conceptual foundations.
AB  - Remarkable progress in the mathematics and computer science of probability has
      led to a revolution in the scope of probabilistic models. In particular,
      'sophisticated' probabilistic methods apply to structured relational systems such
      as graphs and grammars, of immediate relevance to the cognitive sciences. This
      Special Issue outlines progress in this rapidly developing field, which provides
      a potentially unifying perspective across a wide range of domains and levels of
      explanation. Here, we introduce the historical and conceptual foundations of the
      approach, explore how the approach relates to studies of explicit probabilistic
      reasoning, and give a brief overview of the field as it stands today.

PMID- 16807065
TI  - Case studies in current drug development: 'glycylcyclines'.
AB  - Glycylcyclines represent a new class of tetracycline antibiotics with potent
      antibacterial activities against resistant pathogens. One of the glycylcyclines,
      Tygacil, was selected for further development and has been approved by the FDA.
      It has an expanded broad-spectrum of antibacterial activity both in vitro and in
      vivo. It is active against a wide range of clinically relevant pathogens
      including Gram-positive, Gram-negative, atypical, and anaerobic bacteria and
      bacterial strains carrying either or both of the two major forms of tetracycline
      resistance (efflux and ribosomal protection). Most importantly, it is active
      against the multiply antibiotic resistant Gram-positive pathogenic bacteria,
      including methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 16807066
TI  - Bacterial resistance: a sensitive issue complexity of the challenge and
      containment strategy in Europe.
AB  - The development of antimicrobial agents has been a key achievement of modern
      medicine. However, their overuse has led to an increasing incidence of infections
      due to antibiotic-resistant microorganisms. Quantitative figures on the current
      economic and health impact of antimicrobial resistance are scant, but it is
      clearly a growing challenge that requires timely action. That action should be at
      the educational, ethical, economic and political level. An important first step
      would be to increase public awareness and willingness to take the necessary
      measures to curb resistance. Hence, studies are needed that would provide solid,
      quantitative data on the societal impact of antibiotic resistance. This review
      discusses the complexity of resistance, identifies its main drivers and proposes
      measures to contain it on a European scale.

PMID- 16807067
TI  - Rho GDP dissociation inhibitors as potential targets for anticancer treatment.
AB  - The Rho GDP dissociation inhibitors (RhoGDIs) are a major class of regulators of
      Rho GTPases and play essential roles in normal cell growth and malignant
      transformation. Although RhoGDIs are known to inhibit Rho activities, recent
      studies indicate that RhoGDIs can also act as positive regulators through their
      ability to target Rho GTPases to specific subcellular membranes or to protect the
      GTPases from degradation by caspases. RhoGDIs are aberrantly expressed in human
      tumors and this may contribute to Rho-induced cancer progression. This review
      will discuss the dual roles of RhoGDIs in the regulation of Rho GTPases,
      highlighting a possible role in regulating tumorigenicity. In addition, the
      potential for targeting RhoGDIs for anticancer therapy will be discussed.

PMID- 16807069
TI  - Retrospective study of survival and treatment pattern in a cohort of patients
      with oral and oropharyngeal tongue cancers from 1987 to 2004.
AB  - This is a retrospective study of patients with oral and oropharyngeal tongue
      cancers who presented to the Royal Adelaide Hospital (RAH) from 1987 to 2004. The
      aims of this study were to determine sociodemographic and tumour characteristics,
      treatment patterns and five-year disease-specific survival of the disease. All
      cases of tongue cancers, including untreated and palliative cases, were
      identified through the Royal Adelaide Hospital Cancer Registry and were included
      in statistical analysis. A total of 212 cases of tongue cancer were identified.
      Patients less than 45 years of age accounted for 15% of cases and had a tendency
      to present with advanced stage disease. Squamous cell carcinoma was the most
      common histological type. Almost 30% of recorded cases were oropharyngeal or base
      of tongue cancers. Nearly half of the patients had advanced stage (III and IV)
      disease at presentation, which was significantly associated with rural area of
      residence, base of tongue sub-site and early diagnostic period. Treatment
      involved a multidisciplinary approach and majority of patients were treated with
      a curative intent. Palliative treatment was more likely to be given to patient
      with oropharyngeal tongue cancers or advance stage disease. There was no
      significant improvement of five-year disease-specific survival over the 18-year
      period. Poorer survival was significantly associated with age 45 years or older,
      oropharyngeal tongue cancers and advanced stage disease. Tongue cancer is an
      important health issue associated with poor survival. Early detection and
      diagnosis is important in order to improve survival rate for this malignancy.

PMID- 16807070
TI  - Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous
      cell carcinoma (OSCC).
AB  - Chromosomal aberrations are known to have an impact on the initiation and
      progression of oral squamous cell carcinoma (OSCC), but individual genes involved
      in OSCC pathogenesis are poorly described. To elucidate the molecular events
      underlying oral carcinogenesis, a set of primary OSCC were screened for distinct
      genetic imbalances by means of array-based comparative genomic hybridisation. For
      this, a DNA array was used containing 812 genomic targets including oncogenes,
      tumour-suppressor genes and chromosomal regions frequently altered in human
      neoplasms. The most frequent aberrations were amplification of MYC, EGFR, CCND1
      and PIK3CA, whereas deletions affected TRAILR1 and ATM. Furthermore, a distinct
      high-level amplification of the fibroblast growth factor receptor 1 (FGFR1) locus
      was detected in two cases. Detailed FISH analysis on OSCC tissue microarray
      sections revealed amplification prevalence for FGFR1 of 17.4% (16/92).
      Furthermore, FGFR1 protein analysis by immunohistochemistry on a TMA containing
      178 OSCC found a high FGFR1 expression in tumours of early t-stadium and UICC
      stage (T1/2 vs. T3/4: p=0.002; SI-II vs. S III-IV: p=0.048). Our results indicate
      that an increase in FGFR1 expression contributes to oral carcinogenesis at an
      early stage of development.

PMID- 16807071
TI  - Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a
      potential diagnostic biomarker.
AB  - CDH13 encodes a cell adhesion molecule, H-cadherin. In this study, we examined
      CDH13 methylation in nasopharyngeal carcinoma (NPC). Methylation specific PCR
      results showed that CDH13 was methylated in 20% (1/5) NPC cell lines, 100% (2/2)
      NPC xenografts and 89.7% (52/58) of the NPC primary tumors, while only methylated
      in 10% (1/10) normal nasopharyngeal epithelia (P<0.05). CDH13 expression in NPC
      cell lines and NPC xenografts analyzed by RT-PCR showed that expressions of CDH13
      were reversely correlated with their methylation status. In CDH13-silenced cell
      line, demethylating agent 5-aza-deoxycytidine could dramatically restore CDH13
      expression. Taken together, CDH13 promoter is aberrantly methylated in NPC both
      in vitro and in vivo, and promoter methylation plays a pivotal role in the
      silencing of H-cadherin expression. Furthermore, the high sensitivity (81%) and
      specificity (0% false positives) of detecting CDH13 methylation from
      nasopharyngeal swabs suggest it could be utilized as a tool for early diagnosis.

PMID- 16807072
TI  - Application of alpha-smooth muscle actin and c-kit in the differential diagnosis
      of adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma.
AB  - The expression of vimentin, alpha-smooth muscle actin (alpha-SMA) and c-kit in
      adenoid cystic carcinomas (AdCCs) and polymorphous low-grade adenocarcinomas
      (PLGAs) was investigated immunohistochemically to evaluate the application of
      these markers to distinguish AdCCs from PLGAs when the histological features are
      equivocal. Tissue specimens of AdCCs and of PLGAs, formalin-fixed and paraffin
      embedded were retrospectively studied using vimentin, alpha-SMA and c-kit.
      Positive staining for alpha-SMA was identified in all AdCCs and 25% of PLGAs. The
      immunoreactivity of c-kit in all positive cases of AdCCs (83%) and PLGAs (41%)
      was more than 50% and less than 50% of tumor cells respectively. The expression
      pattern for both alpha-SMA and c-kit, in tubular structures of AdCCs was
      different of that seen in the same structures in PLGAs. The results of this study
      support the potential application of alpha-SMA and c-kit as an adjunctive aid in
      the differential diagnosis of AdCCs from PLGAs.

PMID- 16807073
TI  - Risk factors for wound infection after oral cancer surgery.
AB  - Wound infection is a common complication after oral cancer surgery and may result
      in significant functional morbidity, poor cosmetic results and prolonged
      hospitalization. The purpose of this study was to identify the most important
      factors contributing to operative wound infections in patients with oral and
      oropharyngeal cancer. A retrospective review of complications in 111 patients
      after oral and oropharynx cancer surgery with an immediate reconstruction is
      presented. Potential risk factors for infection were categorized based on the
      patient, the disease, and the treatment. Flap-related complications developed in
      73 patients (65.76%). Wound infection occurred in 69 (62.12%), and a fistula in
      10 patients (9%). Other complications developed in 41.44% of the patients. The
      analysis of risk factors for the development of infection showed the following
      factors to be significant: male sex, T and S tumour stages, reconstruction,
      tracheostomy, nasogastric tube or gastrostomy feeding and extent of surgery.

PMID- 16807074
TI  - A questionnaire survey of current UK practice for adjuvant radiotherapy following
      surgery for oral and oropharyngeal squamous cell carcinoma.
AB  - A postal questionnaire was sent to 281 members of the British Association of Head
      and Neck Oncologists (BAHNO) to survey, which patients should receive adjuvant
      radiotherapy following primary surgery for oral and oropharyngeal squamous cell
      carcinoma (O&OSCC). Two hundred and one clinicians were involved in decision
      making for adjuvant radiotherapy in O&OSCC, of which, 132 (66%) responded. Apart
      from general agreement that patients with involved margins or extracapsular
      spread (ECS) should have adjuvant radiotherapy and that in patients with small
      tumours with clear margins and no neck metastasis, radiotherapy should be
      avoided, opinion was divided. Considerable variation in opinion in the UK was
      identified for a subgroup of intermediate risk patients as to whether they should
      have adjuvant radiotherapy. The majority of respondents (95%) would consider
      submitting patients to a prospective multi-centre trial. There is a need for
      research regarding adjuvant radiotherapy for O&OSCC patients at intermediate risk
      of relapse following primary surgery.

PMID- 16807075
TI  - Micronuclei, DNA single-strand breaks and DNA-repair activity in mice exposed to
      1,3-butadiene by inhalation.
AB  - We investigated single-strand breaks and endonuclease III-sensitive sites in DNA
      along with gamma-irradiation-specific DNA-repair activity in hepatocytes and
      frequencies of micronuclei in polychromatic bone-marrow erythrocytes of male NMRI
      mice (2 months old, weight 30-35 g) during sub-acute inhalation exposure to 1,3
      butadiene (28 days, 500 mg/m3) and up to 28 days after the exposure.
      Concentrations of 1,3-butadiene in blood, an indicator of internal exposure,
      moderately increased during the exposure period. The most interesting finding was
      that gamma-irradiation-specific DNA-repair activity gradually increased during
      exposure, being significantly higher compared with control levels on days 7 and
      28 of exposure (P = 0.005 and 0.035, respectively), reaching a maximum on day 1
      after the termination of exposure (P = 0.003) and then returning to control
      levels. A significant correlation between gamma-irradiation-specific DNA-repair
      activity and the concentration of 1,3-butadiene in blood (R = 0.866, P = 0.050)
      supports a possible induction of DNA-repair activity by the exposure to 1,3
      butadiene and formation of its metabolites. The initial increase in micronucleus
      frequency (micronuclei per 1000 cells) in the exposed mice continuously decreased
      from 20.4 +/- 5.1 (day 3) to 15.1 +/- 3.2 (day 28) within the exposure period,
      and subsequently from 12.4 +/- 5.1 to 4.6 +/- 1.6 in the period following
      termination of the 1,3-butadiene exposure, while micronucleus frequencies in
      control animals were significantly lower (from 1.7 +/- 1.5 to 4.2 +/- 0.8).

PMID- 16807076
TI  - Environmental pollution affects genetic diversity in wild bird populations.
AB  - Many common environmental pollutants, together with nuclear radiation, are
      recognized as genotoxic. There is, however, very little information on pollution
      related genetic effects on free-living animal populations, especially in
      terrestrial ecosystems. We investigated whether genetic diversity in two small
      insectivorous passerines, the great tit (Parus major) and the pied flycatcher
      (Ficedula hypoleuca), was changed near point sources of heavy metals (two copper
      smelters) or radioactive isotopes (nuclear material reprocessing plant). We
      measured concentration of heavy metals and nucleotide diversity in mitochondrial
      DNA in feather samples taken from nestlings in multiple polluted areas and at
      control sites. In both species, heavy metal concentrations - especially of
      arsenic - were increased in feathers collected at smelter sites. The P. major
      population living near a smelter showed significantly higher nucleotide diversity
      than a control population in an unpolluted site, suggesting increased mutation
      rates in a polluted environment. On the contrary, F. hypoleuca showed reduced
      nucleotide diversity at both smelter sites but increased nucleotide diversity
      near the source of radioactivity. Our results show that heavy metal pollution and
      low level nuclear radiation affect the nucleotide diversity in two free-living
      insectivorous passerines. We suggest that the different response in these two
      species may be due to their different ability to handle toxic compounds in the
      body.

PMID- 16807077
TI  - In vitro genotoxicity of para-phenylenediamine and its N-monoacetyl or N,N'
      diacetyl metabolites.
AB  - para-Phenylenediamine (PPD), a widely used ingredient of oxidative hair dyes, is
      converted by human hepatocytes and in the human epidermis, or after topical
      application to rats, to its N-monoacetylated (MAPPD) and/or N,N'-diacetylated
      (DAPPD) derivatives. We investigated in vitro genotoxic properties of PPD, MAPPD
      and DAPPD in the Ames test, the micronucleus test (MNT) in human lymphocytes and
      the mouse lymphoma assay (Hprt locus, PPD only). Given that MAPPD and DAPPD are
      actual human skin and hepatic metabolites of PPD and represent the substances to
      which humans are systemically exposed, they were tested in the absence of
      metabolic activation. In the Ames test, PPD was slightly mutagenic in Salmonella
      typhimurium strain TA98 in the presence of a rat liver metabolic activation
      system (S-9), whereas MAPPD and DAPPD were negative in all strains. When tested
      up to toxic doses, PPD did not induce mutation at the Hprt locus of L5178Y mouse
      lymphoma cells in two independent experiments, either in the absence or presence
      of S-9, suggesting that PPD is non-mutagenic in mammalian cells. In the in vitro
      micronucleus test, PPD induced micronuclei (MN) in cultured human peripheral
      blood lymphocytes (HL) in the presence of S-9, when tested following 24-h PHA
      stimulation. No increases in MN frequency were observed in the absence of S-9,
      when tested following 24-h PHA stimulation. However, PPD induced MN both in the
      absence and presence of metabolic activation, when tested following 48-h PHA
      stimulation. In contrast, MAPPD and DAPPD did not induce MN in HL when tested up
      to 10mM concentrations or to their limit of solubility, respectively, after
      either 24- or 48-h stimulation. In conclusion, the results of the Ames and MN
      tests confirm that PPD has a slight genotoxic potential in vitro, although it was
      non-mutagenic in mammalian cells. Given that MAPPD and DAPPD were negative in the
      Ames and the MN tests, these acetylated conversion products are considered to be
      detoxified metabolites that are biologically less reactive than the parent
      molecule PPD.

PMID- 16807078
TI  - Geographical distribution of Metagonimus yokogawai and M. miyatai in Shizuoka
      Prefecture, Japan, and their site preferences in the sweetfish, Plecoglossus
      altivelis, and hamsters.
AB  - Sweetfish, Plecoglossus altivelis, obtained from 18 rivers in Shizuoka Prefecture
      were examined for metacercarial infection of 2 flukes, Metagonimus yokogawai and
      Metagonimus miyatai. The infection rate and density of metacercariae in the fish
      were higher in eastern and western regions than in central region of the
      prefecture. After infection of hamsters with metacercariae derived from the
      scale, 98.7% of the adult worms obtained from the intestine was found to be M.
      miyatai. Conversely, from infection with metacercariae from the flesh, 90.0% of
      the worms was M. yokogawai. Since the worms had no exclusivity in the tissues, we
      conclude that the flukes have location preference with the former primarily
      preferring the scale, and the latter the flesh. Fish from two rivers located in
      adjacent areas in the western region had relatively a higher ratio of M.
      yokogawai in the scale relative to other rivers, suggesting an intraspecific
      genetic variation due to geographical isolation. On examination of adult worms in
      the hamster's intestine, M. yokogawai was mainly located towards the anterior
      part of the intestine, unlike M. miyatai, suggesting that in mammalian host too,
      the parasites have site preference.

PMID- 16807079
TI  - Impact of single dose of diethylcarbamazine and other antifilarial drug
      combinations on bancroftian filarial infection variables: assessment after 2
      years.
AB  - The impact of single dose mass drug administration of diethylcarbamazine (DEC),
      DEC with albendazole (ALB), and ivermectin (IVR) with albendazole, was examined
      on the human bancroftian filarial infections in village scale trials in south
      India, from a follow-up study after 2 years. The treatment arms administered with
      DEC alone and DEC+ALB demonstrated long-term benefits in reducing microfilaraemia
      significantly (P<0.05), while antigenaemia reduction was negligible. The arm with
      ALB+IVR did not show such reductions. Among the antigenaemic and microfilaraemic
      individuals, 87% became amicrofilaraemic in DEC+ALB arm, which were higher than
      that observed in the other 2 treatment arms. Among amicrofilaraemics (but Ag+),
      nearly 35% cleared of infection in DEC+ALB, while 26% and 6% in DEC alone and
      IVR+ALB arms, respectively. The drug combination DEC+ALB was observed to
      demonstrate a significant impact in reducing filarial infection even after 2
      years post treatment.

PMID- 16807080
TI  - Spectra and structure of binary azeotropes II. Acetone-n-pentane.
AB  - Acetone and n-pentane from an azeotrope with the mole ratio of 1:3, respectively.
      As the result of this azeotrope formation, some characteristic vibrational modes
      in FT-IR and chemical shifts in 1H NMR changes. The amount of these band and
      signal changes is an indication of the extend of interaction between two
      components and their orientation in unit structure of the cluster. FT-IR and 1H
      NMR spectra of pure substances and their azeotrope were recorded, spectral
      changes analyzed. Unit structure of azeotrope was deduced based on mole ratio,
      boiling point changes of pure components, and spectral changes in fundamental
      frequency and chemical shifts.

PMID- 16807081
TI  - Synthesis and spectroscopic studies of some transition metal complexes of a novel
      Schiff base ligands derived from 5-phenylazo-salicyladehyde and o-amino benzoic
      acid.
AB  - Cu(II), Mn(II), Ni(II), and Zn(II) metal complexes with novel heterocyclic Schiff
      base derived from 5-phenyl azo-salicyladehyde and o-amino benzoic acid have been
      synthesized and characterized on the basis of elemental analyses, electronic, IR,
      and (1)H NMR spectra, and also by aid of scanning electron microscopy (SEM), X
      ray powder diffraction, molar ratio measurements, molar conductivity
      measurements, and thermogravimetric analyses. It has been found that the Schiff
      base behaves as neutral tridentate (ONO) ligand forming chelates with 1:1
      (metal:ligand) stoichiometry.

PMID- 16807082
TI  - C-H...O hydrogen bond in chloroform-triformylmethane complex: blue-shifted or red
      shifted?
AB  - B3LYP/6-311+G** level of theory is used to investigate the C-H...O hydrogen bond
      formed by chloroform and two conformers of triformylmethane (TFM), i.e. cis-TFM
      (concerned with C1 configuration) and trans-TFM (concerned with C2 and C3
      configurations). Polarized continuum model (PCM) is used to study the solvent
      (chloroform) effect on this hydrogen bond. The C3 configuration is more stable
      than the C1 configuration whether the absolute energy or the stabilization energy
      is concerned. For the C1 and C2 configurations this hydrogen bond is of blue
      shifted type both in gas phase and in chloroform solution. For the C3
      configuration this hydrogen bond is of red-shifted type in gas phase but turns
      into blue-shifted type in chloroform solution instead. It's inappropriate to
      simply designate this hydrogen bond as blue-shifted type or red-shifted type.

PMID- 16807083
TI  - Public healthcare in Mozambique: strategic issues in the ICT development during
      managerial changes and public reforms.
AB  - It has been predicted that major introduction of information communication
      technology (ICT) for health care organisations (HCO) over the next 10 years will
      be used to achieve the universal coverage and improve the quality of health care
      delivered to people. Which is the best strategy on ICT transfer, adoption and
      adaptation for the local Mozambican HCO? This paper argues that a sociotechnical
      approach of ICT development can help policy makers and health managers to address
      the technology transfer in a better and more appropriate way to their social
      context and to the public health reforms in progress. The urgency of health care
      demands (e.g. AIDS epidemic) and the institutional changes implemented by the
      Government and the local Ministry of Health (MOH), open a dynamic process of re
      organisation inside the health institutions in the next years. This process needs
      to be monitored and initiatives planned, which places pressure on the evolution
      of health information system (HIS). The increase in the use of ICT can be an ally
      for health managers. The emergence of the open source software (OSS) and the
      recent ICT market trends towards networking may also enable local HCO to better
      face and solve the long process of health care standardisation, which usually
      prepares and accompanies any introduction of ICT. On the other side, the "big
      bang" introduction of electronic packages, devices and software applications may
      be an obstacle framing and anchoring local HCO to external settings, "modern" and
      universal models. Thus, a uniform step-by-step implementation of hospital-based
      health information system is desirable.

PMID- 16807084
TI  - Putting the technical back into socio-technical systems research.
AB  - Socio-technical systems (STS) analysis has provided us with a powerful framework
      with which to analyse the reasons behind the poor acceptability, uptake and
      performance of many information or communication technology systems (ICT).
      However, for the contribution of STS thinking to be more than simply a means of
      critiquing current practices and ICT systems, it needs to also contribute to the
      process of developing new and more effective ICT systems. Specifically, we need
      to develop a formal design language for translating our insights about the socio
      technical nature of work, into design specifications that result in better
      interventions in the work place. We need to get 'technical' about what we mean
      and about what we want from a design, and we need to work alongside technologists
      to shape technology, as well as the processes, organisations and cultures within
      which they will be embedded. Indeed the process of design itself can be seen as a
      socio-technical one, and understanding the decision to design itself may allow us
      one day to stop designing for people, and create STS that sustainably design
      themselves.

PMID- 16807085
TI  - More than just a mouse click: research into work practices behind the assignment
      of medical trust marks on the World Wide Web.
AB  - Hyperlinked web trust marks have been a popular topic of discussion during the
      past 10 years. However, the discussion has focused mostly on what these trust
      marks are not doing in terms of helping patients (or other lay end users) find
      reliable medical information on the web. In this paper, we discuss how this focus
      on patients and their actions with respect to trust marks, has overshadowed, if
      not rendered invisible, what trust marks are doing to educate medical
      site/information providers. We draw on data from ethnographic research conducted
      at the Health on the Net Foundation in 2002 and 2003 in order to explore an
      alternate definition of what it means to be a 'user' of a trust mark and the
      importance of the review process in educating site providers. We argue that
      understanding the work involved in the process of assigning a seal is crucial to
      understanding the role that the seal plays as part of the medical internet.

PMID- 16807086
TI  - An optimal culture condition maintains human hepatocyte phenotype after long-term
      culture.
AB  - BACKGROUND: Long-term culture of primary hepatocytes from various species is
      impeded by a decrease of cell viability and a loss of hepatocyte-specific
      function. The aim of the present study was to investigate whether our optimal
      culture condition (OC) can maintain the phenotype of primary hepatocytes in long
      term culture. METHODS: Primary human hepatocytes were cultured in either
      hepatocyte maintenance medium (HM) or OC for 2-4 weeks. Expression of hepatocyte
      specific genes was determined by real-time quantitative RT-PCR. RESULTS: The
      level of albumin mRNA in human hepatocytes cultured in OC was 11-fold more than
      in HM and gene expression levels of alpha1-antitrypsin and transferrin were at
      approximately 40 and 11% of freshly isolated primary human hepatocytes. Electron
      microscopy revealed that cells in OC displayed hepatocyte properties (e.g.
      polarity, junctional complexes, bile canaliculi and glycogen particles).
      Cytochrome P4501A1/2 activity of hepatocytes cultured in OC was 15- and 17-fold
      higher than in HM at 2 and 4 weeks of culture, and DNA synthesis was higher.
      CONCLUSIONS: Using our optimal culture condition, we were able to maintain the
      phenotype of primary human hepatocytes in long-term culture. They not only
      maintain better liver-specific function, but also retain higher proliferative
      potential.

PMID- 16807087
TI  - Plasma PAF-acetylhydrolase: an unfulfilled promise?
AB  - Plasma Platelet-activating-Factor (PAF)-acetylhydrolase (PAF-AH also named
      lipoprotein-PLA(2) or PLA(2)G7 gene) is secreted by macrophages, it degrades PAF
      and oxidation products of phosphatidylcholine produced upon LDL oxidation and/or
      oxidative stress, and thus is considered as a potentially anti-inflammatory
      enzyme. Cloning of PAF-AH has sustained tremendous promises towards the use of
      PAF-AH recombinant protein in clinical situations. The reason for that stems from
      the numerous animal models of inflammation, atherosclerosis or sepsis, where
      raising the levels of circulating PAF-AH either through recombinant protein
      infusion or through the adenoviral gene transfer showed to be beneficial.
      Unfortunately, neither in human asthma nor in sepsis the recombinant PAF-AH
      showed sufficient efficacy. One of the most challenging questions nowadays is as
      to whether PAF-AH is pro- or anti-atherogenic in humans, as PAF-AH may possess a
      dual pro- and anti-inflammatory role, depending on the concentration and the
      availability of potential substrates. It is equally possible that the plasma
      level of PAF-AH is a diagnostic marker of ongoing atherosclerosis.

PMID- 16807088
TI  - Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated
      linoleic acid and show anti-obesity effects in diet-induced obese mice.
AB  - Many previous studies have reported that conjugated linoleic acid could be
      produced by starter culture bacteria, but the effects of the bacteria were not
      investigated. Moreover, there was no evidence of the conjugated linoleic acid
      producing bacteria having potential health or nutritional effects related to
      conjugated linoleic acid, including reducing body fat. Here, we investigated the
      anti-obesity effect of Lactobacillus rhamnosus PL60, a human originated bacterium
      that produces t10, c12-conjugated linoleic acid, on diet-induced obese mice.
      After 8 weeks of feeding, L. rhamnosus PL60 reduced body weight without reducing
      energy intake, and caused a significant, specific reduction of white adipose
      tissue (epididymal and perirenal). Although the size of epididymal adipocytes was
      not reduced by L. rhamnosus PL60, apoptotic signals and UCP-2 mRNA levels
      increased in adipose tissue. Liver steatosis, a well known side effect of CLA,
      was not observed by L. rhamnosus PL60 treatment; on the contrary it seemed to be
      normalized. Results showed that the amount of conjugated linoleic acid produced
      by Lactobacillus rhamnosus PL60 was enough to produce an anti-obesity effect.

PMID- 16807090
TI  - Membrane and juxtamembrane targeting by PH and PTB domains.
AB  - Modular pleckstrin homology (PH) and phospho-tyrosine binding (PTB) domains are
      present in a remarkably large number of proteins from yeast to humans. With a
      common core fold, these domain families have evolved to recognize membrane
      embedded phospholipids, in particular phosphoinositides, peripheral membrane
      proteins, and peptide motifs in juxtamembrane regions of integral membrane
      proteins. As the result of intensive investigation using biochemical,
      biophysical, and structural approaches, common ligand recognition principles have
      emerged along with insights into the structural variations that account for the
      diversity of ligand specificities. Analyses of membrane targeting in cells have
      revealed additional determinants beyond the primary ligand binding sites. In this
      review, we highlight unifying recognition principles and further illustrate with
      examples how divergent mechanisms contribute to membrane and juxtamembrane
      targeting by PH and PTB domains.

PMID- 16807091
TI  - Event-related desynchronization/synchronization during an auditory-verbal working
      memory task in mild Parkinson's disease.
AB  - OBJECTIVE: Event-related desynchronization (ERD) and synchronization (ERS) were
      studied during an auditory-verbal working memory task in patients suffering from
      Parkinson's disease (PD). METHODS: PD patients (n=7, mean age 59) at a mild stage
      of the disease volunteered in the study. A group of healthy subjects (n=10, mean
      age 61) served as control group. ERD and ERS of the 1-25 Hz EEG frequencies were
      studied using wavelet transforms during memory encoding and retrieval. RESULTS:
      Both groups performed equally well on the memory task. Statistically significant
      differences in ERD/ERS responses were observed in posterior electrodes during
      encoding of the memory set due to the fact that alpha ( approximately 10-15 Hz)
      ERS was elicited in the controls, but not in the PD group. In broad frequency
      bands ( approximately 6-25 Hz) ERD responses were observed in both groups during
      memory retrieval. A pre-stimulus alpha ERS seen in the control group was absent
      in the PD group. CONCLUSIONS: The results of this preliminary study indicate that
      Parkinson's disease might affect brain oscillatory responses in the alpha
      frequency range in the encoding phase of auditory-verbal working memory.
      SIGNIFICANCE: The ERD/ERS patterns may reflect neurophysiological alterations in
      the processes underlying working memory deficits in PD.

PMID- 16807089
TI  - Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc
      depletion.
AB  - The synthesis of phospholipids in the yeast Saccharomyces cerevisiae is regulated
      by zinc, an essential mineral required for growth and metabolism. Cells depleted
      of zinc contain increased levels of phosphatidylinositol and decreased levels of
      phosphatidylethanolamine. In addition to the major phospholipids, the levels of
      the minor phospholipids phosphatidate and diacylglycerol pyrophosphate decrease
      in the vacuole membrane of zinc-depleted cells. Alterations in
      phosphatidylinositol and phosphatidylethanolamine can be ascribed to an increase
      in PIS1-encoded phosphatidylinositol synthase activity and to decreases in the
      activities of CDP-diacylglycerol pathway enzymes including the CHO1-encoded
      phosphatidylserine synthase, respectively. Alterations in the minor vacuole
      membrane phospholipids are due to the induction of the DPP1-encoded
      diacylglycerol pyrophosphate phosphatase. These changes in the activities of
      phospholipid biosynthetic enzymes result from differential regulation of gene
      expression at the level of transcription. Under zinc-deplete conditions, the
      positive transcription factor Zap1p stimulates the expression of the DPP1 and
      PIS1 genes through the cis-acting element UAS(ZRE). In contrast, the negative
      regulatory protein Opi1p, which is involved in inositol-mediated regulation of
      phospholipid synthesis, represses the expression of the CHO1 gene through the cis
      acting element UAS(INO). Regulation of phospholipid synthesis may provide an
      important mechanism by which cells cope with the stress of zinc depletion, given
      the roles that phospholipids play in the structure and function of cellular
      membranes.

PMID- 16807092
TI  - Role of corpus callosum in interhemispheric coherent activity during sleep.
AB  - OBJECTIVE: To investigate to what extent the increase in interhemispheric
      coherent activity observed from wakefulness to sleep depends on the integrity of
      the corpus callosum (CC). METHODS: Interhemispheric coherent activity was
      analyzed in two epileptic patients selected for callosotomy because of multifocal
      refractory epilepsy, before and 4 months after callosotomy. One patient underwent
      complete callosotomy and another was subjected to callosotomy of the anterior
      2/3, which offered the possibility of comparing the role of the CC in the
      coherent activity increase from wakefulness to sleep, between anterior regions
      with interrupted CC communication (in the two patients) and posterior regions
      with intact communication (in one of them). Results were compared with a group of
      normal subjects. RESULTS: Both patients showed increased coherent activity from
      wakefulness to sleep after surgery. CONCLUSIONS: Results demonstrate that
      interhemispheric coherent activity, despite an attenuation after surgery, is
      higher during SWS than during wakefulness after sectioning the CC; however, they
      have to be taken with caution because they come from two patients only.
      SIGNIFICANCE: Present results show that the increase in coherent activity during
      sleep does not depend exclusively on callosal integrity but also on state
      dependent influences from sleep-promoting mechanisms, probably spread throughout
      the thalamo-cortical network.

PMID- 16807094
TI  - Trigeminal sensory pathway function in patients with SUNCT.
AB  - OBJECTIVE: Short-lasting unilateral neuralgiform headache with conjunctival
      injection and tearing (SUNCT) is a rare primary headache whose origins are
      unclear. To seek information on its pathophysiology, we studied the trigeminal
      Abeta and Adelta pathways by recording trigeminal reflexes and laser evoked
      potentials (LEPs) in patients with SUNCT. METHODS: Trigeminal reflexes and LEPs
      were recorded in 11 consecutive patients. Ten patients had neuroimaging evidence
      documenting idiopathic SUNCT and one had a posterior fossa tumour that compressed
      the trigeminal nerve thus causing symptomatic SUNCT. RESULTS: Whereas the
      patients with idiopathic SUNCT had normal trigeminal reflex and LEP responses,
      the patient with symptomatic SUNCT had abnormal responses. CONCLUSIONS: Our
      neurophysiological findings show that idiopathic SUNCT spares the trigeminal
      sensory pathways whereas symptomatic SUNCT does not. SIGNIFICANCE:
      Neurophysiological testing can easily differentiate the idiopathic and
      symptomatic forms of SUNCT. It also suggests that the two forms are
      pathophysiologically distinct entities.

PMID- 16807095
TI  - Modulation of electrically induced pain by paired pulse transcranial magnetic
      stimulation of the medial frontal cortex.
AB  - OBJECTIVE: Aim of this study was to investigate whether paired pulse transcranial
      magnetic stimulation (ppTMS) applied over the medial frontal cortex (MFC) affects
      acute Adelta fiber-mediated electrically induced pain. In addition, we
      investigated whether this effect depends on the time course of the stimulation,
      on the noxious stimulus intensity or on the ppTMS intensity. METHODS: For painful
      stimulation, the electrical stimulus for the nociceptive flexion reflex (NFR) was
      used. PpTMS (ISI: 50 ms) was applied over the medial frontal cortex at different
      intervals ranging from 0 to 1,000 ms following the previous elicited NFR in 10
      healthy volunteers. Three sequences at 3 different NFR stimulus intensities (at
      NFR threshold, 1.3 x and 1.6 x NFR threshold) with a ppTMS stimulus intensity at
      1.2 x resting motor threshold (RMT) and one sequence with elevated ppTMS at 1.6 x
      RMT stimulus intensity were performed. Pain intensity and pain unpleasantness
      were assessed by visual analogue scales. RESULTS: Pain ratings differed in
      dependence of the interstimulus interval between NFR and ppTMS. Post-hoc t-tests
      revealed an increased verbal pain report within interstimulus intervals from 25
      to 75 ms at NFR threshold as well as for 25 ms at 1.3 x NFR threshold when ppTMS
      was applied at 1.2 x RMT and from 0 to 75 ms at 1.6 x NFR threshold when ppTMS
      was applied at 1.6 x RMT. CONCLUSIONS: The present data suggest that ppTMS over
      MFC-applied in a certain time window-can enhance pain perception of acute Adelta
      fiber-mediated electrically induced pain. We hypothesize that the increase of
      pain is due to interference between ppTMS and the incoming nociceptive input.
      Further pain processing might be modulated by direct effects on MFC or indirect
      effects on anterior cingulate cortex (ACC) or spinal nociception. SIGNIFICANCE:
      Brain areas involved in cognitive and emotional adaptation to pain can be used,
      in place of primary motor areas, as cortical targets in TMS trials of
      experimental or ongoing pain.

PMID- 16807097
TI  - Electrical impedance myography: transitioning from human to animal studies.
AB  - OBJECTIVE: To determine the feasibility of performing electrical impedance
      myography (EIM) in rats. METHODS: EIM was performed on the hamstring muscles of 6
      healthy adult rats with applied frequencies of 2-300 kHz. Studies were performed
      over a 6-week period, with 3 rats having recordings made from the skin (surface
      EIM) and 3 with recordings directly from the muscle (direct-muscle EIM). In
      addition, sciatic nerve crush was performed on one rat and comparisons made pre-
      and post-injury. Reactance and resistance were measured and the primary outcome
      variable, the phase angle (theta), calculated. RESULTS: EIM patterns in the rat
      hamstring muscles were qualitatively similar to those observed in human subjects.
      This held true for both surface and direct-muscle recordings, although direct
      muscle data appeared less repeatable. Sciatic nerve crush data in the single rat
      showed a dramatic reduction in phase and a relative loss of frequency-dependence.
      CONCLUSIONS: EIM data similar to that obtained from human subjects can be
      acquired from rat muscles with surface recordings proving more consistent and
      easier to obtain than direct-muscle recordings. Changes seen with sciatic nerve
      crush mirror those seen in patients with neurogenic injury. SIGNIFICANCE: These
      results support the possibility of performing EIM on rat models of neuromuscular
      disease.

PMID- 16807098
TI  - Nonconvulsive status epilepticus in Creutzfeldt-Jakob disease.

PMID- 16807099
TI  - Auditory processing during deep propofol sedation and recovery from
      unconsciousness.
AB  - OBJECTIVE: Using evoked potentials, this study investigated effects of deep
      propofol sedation, and effects of recovery from unconsciousness, on the
      processing of auditory information with stimuli suited to elicit a physical MMN,
      and a (music-syntactic) ERAN. METHODS: Levels of sedation were assessed using the
      Bispectral Index (BIS) and the Modified Observer's Assessment of Alertness and
      Sedation Scale (MOAAS). EEG-measurements were performed during wakefulness, deep
      propofol sedation (MOAAS 2-3, mean BIS=68), and a recovery period. Between deep
      sedation and recovery period, the infusion rate of propofol was increased to
      achieve unconsciousness (MOAAS 0-1, mean BIS=35); EEG measurements of recovery
      period were performed after subjects regained consciousness. RESULTS: During deep
      sedation, the physical MMN was markedly reduced, but still significant. No ERAN
      was observed in this level. A clear P3a was elicited during deep sedation by
      those deviants, which were task-relevant during the awake state. As soon as
      subjects regained consciousness during the recovery period, a normal MMN was
      elicited. By contrast, the P3a was absent in the recovery period, and the P3b was
      markedly reduced. CONCLUSIONS: Results indicate that the auditory sensory memory
      (as indexed by the physical MMN) is still active, although strongly reduced,
      during deep sedation (MOAAS 2-3). The presence of the P3a indicates that
      attention-related processes are still operating during this level. Processes of
      syntactic analysis appear to be abolished during deep sedation. After propofol
      induced anesthesia, the auditory sensory memory appears to operate normal as soon
      as subjects regain consciousness, whereas the attention-related processes indexed
      by P3a and P3b are markedly impaired. SIGNIFICANCE: Results inform about effects
      of sedative drugs on auditory and attention-related mechanisms. The findings are
      important because these mechanisms are prerequisites for auditory awareness,
      auditory learning and memory, as well as language perception during anesthesia.

PMID- 16807100
TI  - Event-related potential correlates of depression, insight and negative symptoms
      in males with recent-onset psychosis.
AB  - OBJECTIVE: The neurobiology of clinical characteristics -in particular
      depression, insight and negative symptoms- in recent-onset psychosis (ROP) was
      studied using event-related potentials (ERPs). METHODS: Twenty right-handed ROP
      men and 20 controls completed an auditory-oddball task. ROP men had minimum
      exposure to antipsychotic medication. N100, N200 and P300 were studied to
      ascertain the effects of (a) diagnosis (patients versus controls), and (b)
      clinical characteristics. RESULTS: ROP men had significantly lower anterior N100,
      enhanced N200 at T3, and lower P300 at Pz than controls. Lower right-anterior
      N100 and enhanced right-anterior N200 amplitude explained 47.7% of negative
      symptoms. Left-central N100 amplitude explained 30.28% of negative symptoms.
      Lower left-posterior and higher right-posterior P300 amplitude explained 65.99%
      of total symptoms. Lower left-central N100, enhanced left-central N200 and
      depression explained 78.8% of impairments in insight and judgement. Impaired
      insight/judgement correlated positively with right-anterior N200 and was
      identified as the most significant co-efficient for depression. CONCLUSIONS:
      Disturbed selective-attention and executive function indexed by N100 and N200,
      respectively, are associated with poor insight and negative symptoms. A complex
      interaction exists between insight and depression. SIGNIFICANCE: The current
      results demonstrate a biological basis of insight and depression and a complex
      interaction between the two, perhaps mediated by executive function, in early
      psychosis.

PMID- 16807101
TI  - Increase in high frequency EEG activity explains the poor performance of EEG
      spectral entropy monitor during S-ketamine anesthesia.
AB  - OBJECTIVE: To study the effects of S-ketamine on the EEG and to investigate
      whether spectral entropy of the EEG can be used to assess the depth of hypnosis
      during S-ketamine anesthesia. METHODS: The effects of sub-anesthetic (159 (21);
      mean (SD) ng/ml) and anesthetic (1,959 (442) ng/ml) serum concentrations of S
      ketamine on state entropy (SE), response entropy (RE) and classical EEG spectral
      power variables (recorded using the Entropy Module, GE Healthcare, Helsinki,
      Finland) were studied in 8 healthy males. These EEG data were compared with EEG
      recordings from 6 matching subjects anesthetized with propofol. RESULTS: The
      entropy values decreased from the baseline SE 85 (3) and RE 96 (3) to SE 55 (18)
      and RE 72 (17) during S-ketamine anesthesia but both inter- and intra-individual
      variation of entropy indices was wide and their specificity to indicate
      unconsciousness was poor. Propofol induced more pronounced increase in delta
      power (P<0.02) than S-ketamine, whereas anesthetic S-ketamine induced more high
      frequency EEG activity in the gamma band (P<0.001). Relative power of 20-70 Hz
      EEG activity was associated with high SE (P=0.02) and RE (P=0.03) values during S
      ketamine anesthesia. CONCLUSIONS: These differences in low and high frequency EEG
      power bands probably explain why entropy monitor, while adequate for propofol, is
      not suitable for assessing the depth of S-ketamine anesthesia. SIGNIFICANCE: The
      entropy monitor is not adequate for monitoring S-ketamine-induced hypnosis.

PMID- 16807102
TI  - Minimization of cochlear implant stimulus artifact in cortical auditory evoked
      potentials.
AB  - OBJECTIVE: To compare two methods of minimizing cochlear implant artifact in
      cortical auditory evoked potential (CAEP) recordings. METHODS: Two experiments
      were conducted. In the first, we assessed the use of independent component
      analysis (ICA) as a pre-processing filter. In the second, we explored the use of
      an optimized differential reference (ODR) for minimizing artifacts. RESULTS: Both
      ICA and the ODR can minimize the artifact and allow measurement of CAEP
      responses. CONCLUSIONS: When using a large number of recording electrodes ICA can
      be used to minimize the implant artifact. When using a single electrode montage
      an optimized differential reference is adequate to minimize the artifact.
      SIGNIFICANCE: The use of an optimized differential reference could allow cortical
      evoked potentials to be used in routine clinical assessment of auditory pathway
      development in children and adults fit with cochlear implants.

PMID- 16807103
TI  - Indirect ultrasound measurement of humeral torsion in adolescent baseball players
      and non-athletic adults: reliability and significance.
AB  - Accurate clinical interpretation of shoulder rotation range requires knowledge of
      the contribution of humeral torsion. This study compares the reliability of
      indirectly measuring humeral torsion using ultrasound visualisation with direct
      palpation and compares the degree of humeral torsion in a non-throwing adult
      population with a population of elite adolescent baseballers. The reliability of
      a novel method of indirectly measuring humeral torsion using palpation and
      ultrasound was established prior to using the ultrasound method to determine the
      amount of humeral torsion in both humeri of a group of 16 non-throwing subjects
      and 36 elite adolescent baseball players. Excellent inter-tester reliability was
      found for the ultrasound method of measuring humeral torsion in each arm (ICC
      2,1: 0.98 and 0.94) but poor reliability for the direct palpation method (ICC
      2,1: 0.51 and 0.49). Using the ultrasound method, side-to-side differences in
      humeral torsion ranged from 0 to 13 degrees for the non-throwing group and 0 to
      29 degrees for the baseball players. This side-to-side difference was significant
      in the baseball players (p<0.001) but not significant in the non-throwing group
      (p=0.43). Whilst side-to-side differences in humeral torsion were noted between
      all subjects irrespective of arm dominance, only throwers demonstrated
      consistently greater humeral retrotorsion in their throwing arm. A reliable
      clinical tool for estimating humeral torsion, such as that employed in this
      study, will allow for a more valid prescription of interventions for the
      treatment of shoulder dysfunction.

PMID- 16807104
TI  - Characteristics of anterior cruciate ligament injuries in Australian football.
AB  - Anterior cruciate ligament (ACL) injuries are the most costly injuries in
      football at both professional and amateur levels (Orchard J, Seward H, McGivern
      J, Hood S. Intrinsic and extrinsic risk factors for anterior cruciate ligament
      injury in Australian footballers. Am J Sports Med 2001;29:196-200.). In this
      study video analysis of 34 ACL injuries in Australian football was performed to
      investigate the causes of these injuries. Factors that may have contributed to
      the cause of the injury were analysed, rated and reported. The factors analysed
      were: type of manoeuvre, direction the knee 'gave way', running speed, knee
      angle, cutting angle and if the player was accelerating or decelerating. The
      majority of the injuries analysed occurred in non-contact situations (56%). Of
      these 37% occurred during sidestepping manoeuvres, 32% in landing, 16% land and
      step, 10% stopping/slowing and 5% crossover cut manoeuvres. Ninety-two percent of
      the non-contact injuries occurred at extended knee angles of 30 degrees or less,
      which is also commonly known to place stress on the ACL and reduce the protective
      role of hamstrings. Over half (54%) of non-contact injuries occurred whilst
      decelerating. It would be expected that greater speed and angle cut too would
      increase the frequency of ACL injury. The results could not confirm this with
      most injuries occurring at running speeds of slow jogging to running and equal
      number of injuries occurred at cutting to angles of the ranges 15-45 degrees and
      45-75 degrees. These results give greater understanding into potential causes or
      contributors of ACL injury and information to assist in the development of knee
      injury prevention programs.

PMID- 16807105
TI  - Reliability and validity of the Chinese version of IPAQ (short, last 7 days).
AB  - The aim of this study was to examine the reliability and validity of the Chinese
      version of the International Physical Activity Questionnaire (IPAQ-C). The IPAQ-C
      was administered three times to each participant to examine the stability and
      reliability of the self-reported physical activity, whilst data to examine
      concurrent validity were acquired over 7 consecutive days using a physical
      activity log (PA-log), and an MTI accelerometer. A complete set of data was
      obtained from 49 Chinese residents (range 15-55 years; 30 males). The total
      physical activity recorded by IPAQ-C was acceptably reliable (ICC of 0.79 and %CV
      of 26%). There was weak agreement between IPAQ-C and the total MTI-derived
      activity and any of its constituent sub-components. Better agreement was seen
      between IPAQ-C and the PA-log data, with no significant difference between
      average total activity (3931 and 4047 MET min week(-1), respectively, p=0.51),
      and a bias and LOA of 3% and 94% of the mean score, respectively. Although these
      statistics are not dissimilar to those reported on other self-report physical
      activity questionnaires, suggesting the IPAQ-C is adequately reliable and valid
      for the measurement of total physical activity in a Chinese population, care
      needs to be taken, especially as the sub-components of total activity were
      markedly less valid and reliable.

PMID- 16807106
TI  - Supportive care for patients with oesophageal and other upper gastrointestinal
      cancers: The role of a specialist nurse in the team.
AB  - The care pathway of patients with upper gastrointestinal cancers is complex. We
      retrospectively evaluated the patients' opinions of support and supportive care
      given by a specialist nurse who led the care of such patients. A study-specific
      questionnaire addressed the support given by the specialist nurse and other
      professionals in the team before, during and after treatment. Virtually all 73
      responders considered the support of the specialist nurse important (87-94%).
      This support seemed more appreciated than that of outpatient clinic (P = 0.00)
      and surgical ward staff (P = 0.01) during the diagnostic phase, and during the
      follow-up it became more important than that of all other team professionals. A
      second study-specific questionnaire assessed the supportive care. Of 49 patients,
      71-94% completely agreed that the supportive care given by the specialist nurse
      was satisfactory, and 90-100% considered it important. Whereas 10% had difficulty
      in understanding physicians' information, none had such problems regarding
      information given by the nurse (P = 0.09). Review of documented contacts between
      the specialist nurse and 75 patients with oesophago-gastric cancer revealed that
      contacts were frequent during follow-up, and nutritional problems predominated.
      Thus, specialist nurses can be recommended as leaders of the care pathway of
      patients with upper gastrointestinal cancers.

PMID- 16807107
TI  - The DARC conspiracy--virus invasion tactics.
AB  - Is there a "conspiracy" at work among viral pathogens? Apparently, yes. Rabies
      virus, lenti- and retroviruses, and herpesviruses, the "co-conspirators", target
      select members of the tumor necrosis factor (TNF) receptor superfamily to invade
      the cells of their host. The intrigue deepens, as several reports have revealed
      that the viral envelope proteins interact with the cellular TNF receptor in a
      highly conserved region of previously unknown function. Targeting of this region
      by diverse pathogens suggests that a selective advantage is acquired. This
      advantage might involve regulation of the immune response, because recent
      investigations of the herpesvirus entry receptor demonstrated that this conserved
      region engages an inhibitory co-receptor governing T-cell activation.

PMID- 16807108
TI  - TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate
      immunity.
AB  - Significant advances in our understanding of innate immunity have been made
      following the identification of three families of pathogen sensors: Toll-like
      receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs).
      Members of the TLR family recognize bacteria, viruses, fungi and protozoa; NLRs
      with known functions detect bacteria, and RLRs are anti-viral. It is likely that
      interplay between these families ensures the efficient co-ordination of innate
      immune responses, through either synergistic or co-operative signalling.
      Important interactions occur between TLRs and certain NLRs for inducing the pro
      inflammatory cytokine interleukin (IL)-1beta. TLRs induce pro-IL-1beta production
      and prime NLR-containing multi-protein complexes, termed "inflammasomes", to
      respond to bacterial products and products of damaged cells. This results in
      caspase-1 activation and the subsequent processing of pro-IL-1beta to its active
      form. In this article, we hypothesize that during the first phase of the host
      response to infection, an important interplay occurs between these families,
      providing a substantial combinatorial repertoire in innate immunity.

PMID- 16807109
TI  - T cells climb on board Blimp-1.
AB  - B lymphocyte-induced maturation protein (Blimp)-1, a transcriptional repressor,
      has long been known to drive the terminal maturation of B cells into plasma
      cells. However, two recent studies reveal an unanticipated role for Blimp-1 in T
      cell homeostasis. Blimp-1-deficient T cells exhibit enhanced proliferative and
      functional responses following activation, and induce spontaneous colitis. Hence,
      aside from its role in B-cell differentiation, Blimp-1 directs restraint among T
      cells.

PMID- 16807111
TI  - Commentary on the current opinions on blood components safety/efficacy.

PMID- 16807112
TI  - Development of a mock hemopoietic stem cell component suitable for the validation
      of cryopreservation procedures.
AB  - We developed a laboratory model of a unit of hemopoietic progenitor cells (mock
      HPC unit) suitable for the validation of HPC cryopreservation procedures. The
      project was prompted by the practical and ethical difficulty of using real HPC
      units collected from healthy donors and patients for validation purposes. Mock
      HPC units of different volumes ranging from about 120 to about 540mL were
      prepared by pooling a routinely discarded by product of our procedure to prepare
      platelet concentrates from buffy-coats, a standard procedure in most blood
      centers in Europe. Five ABO/Rh identical buffy coats each of 50mL volume,
      obtained from 450mL whole blood units by hard spin, were pooled with 300mL of a
      commercial platelet additive solution. After soft spin, the supernatant platelet
      concentrate pool was removed. The bottom fraction of this procedure, which
      contains RBC, WBC, HPC and platelets, constitutes a mock-HPC unit of about 120mL
      volume. Several bottom fractions may be pooled to obtain a mock-HPC unit of the
      desired volume. We used 20 mock-HPC units to validate an automatic procedure of
      HPC cryopreservation with a controlled rate freezer. In particular, we documented
      the standardization of critical points of the cooling profile, such as the
      correspondence of the crystallization phase with the theoretical freezing
      temperature of the product, the temperature peak rise above the theoretical
      freezing temperature of -5.7 degrees C and the automatic achievement in the
      chamber of a constant minimum temperature during supercooling (about -37 degrees
      C) with mean chamber loading volumes ranging from 231.8 to 1027.2mL.

PMID- 16807114
TI  - Pondering probiotics.

PMID- 16807113
TI  - Potent antitumor activity of a tumor-specific soluble TCR/IL-2 fusion protein.
AB  - We previously have generated a single-chain T cell receptor-cytokine fusion
      protein (264scTCR/IL-2) comprising interleukin-2 genetically linked to a soluble
      HLA-A2.1-restricted TCR recognizing a peptide of human p53 protein. In this
      report, we show that 264scTCR/IL-2 inhibits the growth of primary tumors derived
      from the A375 (p53+/HLA-A2.1+) human melanoma and exhibits significantly better
      antitumor activity than recombinant human IL-2 alone. Moreover, treatment with
      264scTCR/IL-2 results in tumor growth retardation in mice bearing large A375
      tumors and other p53+/HLA-A2.1+ human tumors but does not affect tumor outgrowth
      of HLA-A2.1-negative tumors. This suggests that antigen targeting plays a
      substantial role in the efficacy of 264scTCR/IL-2 against p53+/HLA-A2+ tumors.
      Further, the antitumor activity of 264scTCR/IL-2 was found to be likely mediated
      by NK cell activation and tumor infiltration. A biologically active chimeric
      version of the molecule (c264scTCR/IL-2) also exhibits favorable pharmacokinetic
      properties required of a clinical candidate for this novel class of potent
      antitumor activities and targeted anticancer immunotherapeutics.

PMID- 16807115
TI  - Macrophage migration inhibitory factor has a proinflammatory activity via the p38
      pathway in glucocorticoid-resistant ulcerative colitis.
AB  - Macrophage migration inhibitory factor (MIF) is a cytokine that has potent anti
      steroid effects and might be implicated in the pathogenesis of Ulecrative colitis
      (UC). We defined the functional role of MIF in the glucocorticoid (GC)-resistant
      inflammatory response in UC. Twenty-four colonic samples were obtained from GC
      responsive cases, GC refractory cases, Crohn's disease and controls. LPMC were
      isolated from surgical specimens. MIF was strongly expressed at mRNA levels in
      refractory cases rather than responsive cases with UC and controls. IL-8
      production from LPMC was significantly reduced by GC addition in responsive cases
      but not in refractory cases. In refractory cases, anti-MIF Ab ameliorated GC
      resistant IL-8 production and p38-MAPK activity of LPMC. In addition, p38-MAPK
      antagonist SB230580 also ameliorated GC-resistant IL-8 production. These results
      suggest that MIF has an additional proinflammatory activity through the p38-MAPK
      pathway in GC-resistant UC.

PMID- 16807116
TI  - Specific inhibition of nonsense-mediated mRNA decay components, SMG-1 or Upf1,
      rescues the phenotype of Ullrich disease fibroblasts.
AB  - Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that
      degrades aberrant mRNAs containing premature translation termination codons
      (PTCs). The essential proteins for NMD include SMG-1, a protein kinase, and Upf1,
      a substrate of SMG-1 with RNA helicase activity. In this study, we evaluated the
      effects of NMD inhibition by siRNA-mediated knockdown of SMG-1 or Upf1 on the
      phenotype of Ullrich disease, an autosomal recessive congenital muscular
      dystrophy. The patient studied showed a homozygous frameshift mutation with a PTC
      in the collagen VI alpha2 gene, which encodes a truncated but partially
      functional protein. The patient's fibroblasts showed a nearly complete loss of
      the triple-helical collagen VI protein and functional defects in the
      extracellular matrix (ECM) due to the crucial deficiency of the collagen VI
      alpha2 protein. We have shown that siRNA-mediated knockdown of SMG-1 or Upf1
      causes the up-regulation of the mutant triple-helical collagen VI, resulting in
      the formation of partially functional ECM. We suggest that the inhibition of NMD
      may be useful as a therapeutic approach to treat some human genetic diseases
      exacerbated by NMD.

PMID- 16807117
TI  - Serial analysis of gene expression in progressing and regressing mouse tumors
      implicates the involvement of RANTES and TARC in antitumor immune responses.
AB  - Previously we demonstrated that gene transduction of the granulocyte-macrophage
      colony stimulating-factor (GM-CSF) gene into mouse tumor cells eliminated
      tumorigenicity in vivo. The rejection process of the subcutaneous tumor was as
      follows: transient tumor growth peaked around 10 days after tumor injection, then
      the tumors were rejected within a week. In this paper, we analyzed the gene
      expression of the transiently established tumor masses by the serial analysis of
      gene expression method to identify molecules associated with the antitumor
      effect. We then screened those genes that were differentially expressed between
      the parental and the GM-CSF-transduced tumors and identified a group of genes
      that are suggested to have a relationship with tumor rejection, including a
      cytokine receptor, adhesion molecules, chemokines, cytotoxicity-related
      molecules, and others. Focusing on the chemokine genes TARC and RANTES, which
      were preferentially expressed in the GM-CSF-transduced tumors, their forced
      expression on mouse tumor cells showed moderate suppression of tumor formation.
      Transduction of GM-CSF in combination with either the TARC or the RANTES gene
      into tumor cells profoundly inhibited tumor establishment. Histological findings
      suggested the significant contribution of CD4+ T cells to tumor regression in
      both TARC/GM-CSF- and RANTES/GM-CSF-transduced tumor cells, in excess of that
      seen with GM-CSF transduction alone.

PMID- 16807118
TI  - The mouse dystrophin muscle promoter/enhancer drives expression of mini
      dystrophin in transgenic mdx mice and rescues the dystrophy in these mice.
AB  - Successful gene therapy for Duchenne muscular dystrophy (DMD) requires the
      restoration of dystrophin protein in skeletal muscles. To achieve this goal,
      appropriate regulatory elements that impart tissue-specific transgene expression
      need to be identified. Currently, most muscle-directed gene therapy studies
      utilize the muscle creatine kinase promoter. We have previously described a
      muscle enhancer element (mDME-1) derived from the mouse dystrophin gene that
      increases transcription from the mouse dystrophin muscle promoter. Here, we
      explore the use of this native mouse dystrophin muscle promoter/enhancer to drive
      expression of a human dystrophin minigene in transgenic mice. We show that the
      dystrophin promoter can provide tissue-specific transgene expression and that the
      mini-dystrophin protein is expressed at the sarcolemma of skeletal muscles from
      mdx mice, where it restores the dystrophin-associated glycoprotein complex. The
      level of transgene expression obtained is sufficient to protect mdx muscles from
      the morphological and physiological symptoms of muscular dystrophy, as well as
      from exercise-induced damage. Therefore, the dystrophin muscle promoter/enhancer
      sequence represents an alternative for use in gene therapy vectors for the
      treatment of DMD.

PMID- 16807119
TI  - Adenoviral gene vector tethering to nanoparticle surfaces results in receptor
      independent cell entry and increased transgene expression.
AB  - The present studies investigated the hypothesis that affinity immobilization of
      replication-defective adenoviruses (Ad) on the surfaces of biodegradable
      nanoparticles (NP) can improve transduction through uncoupling cellular uptake
      from the coxsackie-adenovirus receptor (CAR). Ad was tethered to the surfaces of
      polylactide-based NP that were surface-activated using a photoreactive
      polyallylamine-benzophenone-pyridyldithiocarboxylate polymer, which enabled (via
      thiol chemistry) the covalent attachment of Ad-binding proteins, either the
      recombinant D1 domain of CAR or an adenoviral knob-specific monoclonal antibody.
      Gene transfer by NP-Ad complexes was studied in relation to cellular uptake as a
      function of cell type and the character of NP-Ad binding. NP-Ad complexes, but
      not Ad applied with or without control nonimmune IgG-modified NP, significantly
      increased green fluorescent protein reporter expression in endothelioma and
      endothelial and arterial smooth muscle cells (SMC) in direct correlation to the
      extent of NP-Ad internalization. CAR-independent uptake of NP-Ad was confirmed by
      demonstrating inhibition of free Ad- but not NP-Ad complex-mediated transduction
      by knob protein. Complexes formulated with an Ad encoding inducible nitric oxide
      synthase inhibited growth of cultured SMC to a significantly greater extent than
      those with (GFP)Ad or (NULL)Ad or free vector. It is concluded that Ad-specific
      affinity tethering to biodegradable NP can significantly increase the level of
      gene expression via a CAR-independent uptake mechanism.

PMID- 16807120
TI  - The future of cardiovascular imaging and non-invasive diagnosis: a joint
      statement from the European Association of Echocardiography, the Working Groups
      on Cardiovascular Magnetic Resonance, Computers in Cardiology, and Nuclear
      Cardiology, of the European Society of Cardiology, the European Association of
      Nuclear Medicine, and the Association for European Paediatric Cardiology.
AB  - Advances in medical imaging now make it possible to investigate any patient with
      cardiovascular disease using multiple methods which vary widely in their
      technical requirements, benefits, limitations, and costs. The appropriate use of
      alternative tests requires their integration into joint clinical diagnostic
      services where experts in all methods collaborate. This statement summarises the
      principles that should guide developments in cardiovascular diagnostic services.

PMID- 16807121
TI  - Up-regulation of an extracellular superoxide dismutase-like activity in
      hibernating hamsters subjected to oxidative stress in mid- to late arousal from
      torpor.
AB  - Torpor-arousal cycles, one of the inherent features in hibernators, are
      associated with a rapid increase in body temperature and respiration, and it
      would lead to elevation of reactive oxygen species (ROS) generation. However,
      hibernators apparently tolerate this oxidative stress. We have observed in Syrian
      hamsters (Mesocricetus auratus) a maximal temperature shift and respiratory rate
      in mid- to late arousal (16-33 degrees C rectal temperature) from torpor. To
      examine plasma antioxidant status during arousal, we studied total superoxide
      radical-scavenging activity in plasma by electron spin resonance. The superoxide
      radical-scavenging activity reached a maximum at 32 degrees C, coincident with a
      peak in plasma uric acid levels, a ROS generation indicator. The up-regulated
      activity at 32 degrees C was attributable to the peak of the activity eluted at
      260-kDa on gel-filtration chromatography, but was not to small antioxidant
      molecules such as ascorbate and alpha-tocopherol. The activity eluted at 260-kDa
      increased 3-fold at 32 degrees C compared with that of the torpid state, and was
      not detected either at 6 h after the onset of arousal or in the euthermic state.
      Moreover, the activity exhibited extracellular SOD-like properties: its induction
      in plasma by heparin injection and its affinity for heparin. Our results suggest
      that the 260-kDa extracellular SOD-like activity plays a role in the tolerance
      for the oxidative stress during arousal from torpor.

PMID- 16807122
TI  - Enhanced antioxidant defense due to extracellular catalase activity in Syrian
      hamster during arousal from hibernation.
AB  - Mammalian hibernators are considered a natural model for resistance to ischemia
      reperfusion injuries, and protective mechanisms against oxidative stress evoked
      by repeated hibernation-arousal cycles in these animals are increasingly the
      focus of experimental investigation. Here we show that extracellular catalase
      activity provides protection against oxidative stress during arousal from
      hibernation in Syrian hamster. To examine the serum antioxidant defense system,
      we first assessed the hibernation-arousal state-dependent change in serum
      attenuation of cytotoxicity induced by hydrogen peroxide. Serum obtained from
      hamsters during arousal from hibernation at a rectal temperature of 32 degrees C,
      concomitant with the period of increased oxidative stress, attenuated the
      cytotoxicity four-fold more effectively than serum from cenothermic control
      hamsters. Serum catalase activity significantly increased during arousal, whereas
      glutathione peroxidase activity decreased by 50%, compared with cenothermic
      controls. The cytoprotective effect of purified catalase at the concentration
      found in serum was also confirmed in a hydrogen peroxide-induced cytotoxicity
      model. Moreover, inhibition of catalase by aminotriazole led to an 80% loss of
      serum hydrogen peroxide scavenging activity. These results suggest that
      extracellular catalase is effective for protecting hibernators from oxidative
      stress evoked by arousal from hibernation.

PMID- 16807123
TI  - Masculinization of female golden rabbitfish Siganus guttatus using an aromatase
      inhibitor treatment during sex differentiation.
AB  - To elucidate the involvement of endogenous estrogen (estradiol-17beta; E2) and
      the decisive factor (somatic or germinal element) in the ovarian differentiation
      of tropical marine teleosts, the effect of the aromatase inhibitor (AI) fadrozole
      on gonadal sex differentiation in the golden rabbitfish Siganus guttatus (Bloch)
      was examined for different dosages and periods of treatment. Fadrozole
      interrupted ovarian cavity formation at a dose of 500 microg g(-1) diet, while
      there was little effect at 10 or 100 microg g(-1). The gonads from both the 30
      day and 90-day administration (500 microg g(-1) diet) groups were significantly
      biased toward testes (P=0.002 and <0.0001, respectively), which suggests strongly
      that E2 is involved in early ovarian differentiation and that its suppression is
      an indispensable condition for testicular differentiation in S. guttatus. The
      results from the two different AI treatment periods imply that the initial
      feminization of somatic gonadal elements determines subsequent ovarian
      differentiation, including oogenesis: a conclusion supported by the considerable
      time lag between ovarian cavity formation and subsequent oogenesis during normal
      ovarian differentiation in S. guttatus.

PMID- 16807124
TI  - Age- and tissue-dependent metallothionein and cytosolic metal distribution in a
      native Mediterranean fish, Mullus barbatus, from the Eastern Adriatic Sea.
AB  - The levels of metallothionein (MT), a biomarker of metal exposure, and of
      cytosolic metals (Zn, Cu, Cd), known as MT inducers, were investigated as
      variables of age (1 to 8 years) and tissue mass (liver, kidney, brain) of red
      mullet (Mullus barbatus). Within the age from 1 to 8 years the most significant
      increase is evident for cytosolic Cd in liver (43-fold) and in kidney (5-fold).
      MT and essential metals are constant with age or slightly increased. Over the
      growth period, statistically significant MT and metal increase is evident only
      between 1 and 6-8 years old specimens, while for Cd in liver and kidney cytosol
      significant increase already exists at 4 years old specimens. Metal distribution
      in all tissues follows the order: Zn>Cu>Cd, with even 500-800 times lower Cd
      levels than essential metal levels. Consequently, MTs follow the levels of
      essential metals, Zn and Cu, indicating MT involvement in homeostasis of
      essential metals. In contrast to kidney and brain, hepatic MT levels are not age
      dependent. Inclusion of hepatic MT measurements and the associated cytosolic
      metals will be useful in the assessment of long-term metal effects in demersal
      fish M. barbatus.

PMID- 16807125
TI  - Effects of ascorbic acid on impaired vascular reactivity in aortas isolated from
      age-matched hypertensive and diabetic rats.
AB  - Impaired vascular reactivity is a hallmark of several cardiovascular diseases
      that include hypertension and diabetes. This study compared the changes in
      vascular reactivity in age-matched experimental hypertension and diabetes, and,
      subsequently, tested whether these changes could be affected directly by ascorbic
      acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic
      acid effects was also investigated. All the experiments were performed in the
      presence of a cyclooxygenase inhibitor, indomethacin (10 microM). Results showed
      that the endothelium-dependent and -independent relaxations induced by
      acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were blunted to
      a similar extent in isolated aortic rings from age-matched spontaneously
      hypertensive (SHR) (R(max): ACh = 72.83+/-1.86%, SNP = 96.6+/-1.90%) and diabetic
      (Rmax: ACh = 64.09+/-5.14%, SNP = 95.84+/-1.41%) rats compared with aortic rings
      of normal rats (Rmax: ACh = 89%, SNP = 104.0+/-1.0%). The alpha1-receptor
      mediated contractions induced by phenylephrine (PE) were augmented in diabetic
      (Cmax = 148.8+/-9.0%) rat aortic rings compared to both normal (Cmax = 127+/
      6.9%) and SHR (Cmax = 118+/-4.5%) aortic rings. Ascorbic acid pretreatment was
      without any significant effects on the vascular responses to ACh, SNP and PE in
      aortic rings from normal rats. Ascorbic acid significantly improved ACh-induced
      relaxations in SHR (Rmax = 89.09+/-2.82%) aortic rings to a level similar to that
      observed in normal aortic rings, but this enhancement in ACh-induced relaxations
      was only partial in diabetic aortic rings. Ascorbic acid lacked any effects on
      SNP-induced relaxations in both SHR and diabetic aortic rings. Ascorbic acid
      markedly attenuated contractions induced by PE in aortic rings from both SHR
      (Cmax = 92.9+/-6.68%) and diabetic (Cmax = 116.9+/-9.4%) rats. Additionally,
      following inhibition of nitric oxide synthesis with l-NAME, ascorbic acid
      attenuated PE-induced contractions in all aortic ring types studied. These
      results suggest that (1) vascular hyper-responsiveness to alpha(1)-receptor
      agonists in diabetic arteries is independent of endothelial nitric oxide
      dysfunction; (2) ascorbic acid directly modulates contractile responses of
      hypertensive and diabetic rat aortas, likely through mechanisms in part
      independent of preservation of endothelium-derived nitric oxide.

PMID- 16807126
TI  - Ligustilide induces vasodilatation via inhibiting voltage dependent calcium
      channel and receptor-mediated Ca2+ influx and release.
AB  - The purpose of the present study was to investigate the effect of ligustilide on
      vasodilatation in rat mesenteric artery and the mechanisms responsible for it.
      Isometric tension of rat mesenteric artery rings was recorded by a sensitive
      myograph system in vitro. The results showed that ligustilide at concentrations
      more than 10 microM relaxed potassium chloride (KCl)-preconstricted rat
      mesenteric artery in a concentration-dependent manner. The vasodilatation effect
      of ligustilide was not dependent on endothelium. Ligustilide rightwards shifted
      concentration-response curves induced by KCl, calcium chloride (CaCl(2)),
      noradrenaline (NA) or 5-hydroxytryptamine (5-HT) in a non-parallel manner. This
      suggests that the vasodilatation effects were most likely via voltage-dependent
      calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Propranolol,
      glibenclamide, tetraethylammonium and barium chloride did not affect the
      vasodilation induced by ligustilide, showing that beta-adrenoceptor, ATP
      sensitive potassium channel, calcium-activated potassium channel and inwardly
      rectifying potassium channel were not involved in the vasodilatation. Ligustilide
      concentration-dependently inhibited the vasoconstriction induced by NA or CaCl(2)
      in Ca(2+)-free medium, indicating that the vasodilatation relates to inhibition
      of extracellular Ca(2+) influx through VDCC and ROCC, and intracellular Ca(2+)
      release from Ca(2+) store. Since caffeine-induced contraction was inhibited by
      ligustilide, inhibition of intracellular Ca(2+) released by ligustilide occurred
      via the ryanodine receptors. Our results suggest that ligustilide induces
      vasodilatation in rat mesenteric artery by inhibiting the VDCC and ROCC, and
      receptor-mediated Ca(2+) influx and release.

PMID- 16807128
TI  - Targeted inhibition of phosphoinositide 3-kinase activity as a novel strategy to
      normalize beta-adrenergic receptor function in heart failure.
AB  - Human heart failure is a complex clinical syndrome characterized by extensive
      abnormalities in the beta-adrenergic receptor (betaAR) system. Normalization of
      betaAR signalling consistently ameliorates cardiac dysfunction and survival in
      heart failure, suggesting that betaAR dysfunction may be intrinsically linked to
      the deterioration of cardiac performance. Agonist-dependent phosphorylation of
      betaARs by betaAR kinase 1 (betaARK1) initiates the processes of desensitization
      and downregulation, hallmarks of heart failure. Our recent studies have shown
      that betaARK1 forms a cytosolic complex with phosphoinositide 3-kinase (PI3K) and
      that translocation of betaARK1 to the plasma membrane also promotes the betaAR
      targeting of PI3Ks. At the plasma membrane, the generation of 3'-phosphorylated
      phosphatidylinositols by PI3K is required in the process of endocytosis, a
      prodrome to receptor downregulation. A large body of data now indicates that
      betaAR-targeting of PI3Ks is consistently associated with abnormalities of betaAR
      signalling under pathological conditions, including pressure-overload hypertrophy
      and heart failure from different causes. In this review we will discuss the role
      of betaAR-targeted PI3K activity and novel experimental strategies to disrupt the
      betaARK1/PI3K complex and in turn ameliorate betaAR dysfunction and the
      progression of heart failure.

PMID- 16807127
TI  - Early-onset endothelin receptor blockade in hypertensive heterozygous Ren-2 rats.
AB  - Male heterozygous Ren-2 transgenic rats and Hannover Sprague-Dawley rats fed a
      normal or high-salt diet were either untreated or treated with the nonselective
      receptor ET(A)/ET(B) receptor blocker bosentan or the selective ET(A) receptor
      blocker, ABT-627, known as atrasentan. Survival rate was partly increased by
      bosentan and fully normalized by atrasentan. Bosentan did not significantly
      influence the course of hypertension in TGR, whereas atrasentan significantly
      decreased BP on both diets. Atrasentan substantially reduced proteinuria, cardiac
      hypertrophy, glomerulosclerosis and left ventricular ET-1 tissue concentration on
      both diets. Our data indicate that ET(A) receptor blockade is superior to
      nonselective blockade in attenuating hypertension, end-organ damage and improving
      survival rate.

PMID- 16807129
TI  - Optimizing randomized phase II trials assessing tumor progression.
AB  - The traditional development paradigm for phase II trials in oncology has been
      challenged in recent years by the introduction of cytostatic therapies. These
      agents slow the growth of tumors rather than cause high rates of shrinkage, this
      argues for the use of endpoints that measure growth inhibition such as
      progression free survival. We have previously argued the need for randomized
      trials in this setting. Here we discuss methodological solutions to enhance the
      development decision at the end of phase II in the context of progression
      endpoints employed in randomized trials. There are well recognized issues
      associated with progression endpoints relating to bias in the timing and
      interpretation of assessments. In this paper we present design and analysis
      solutions that will minimize bias by using methods that are either partially or
      completely time independent. We also discuss other design features to maximize
      the information yielded in a phase II setting. We advocate the creation of
      progression endpoints that utilize all available progression data rather than
      early fixed time-point analyses and show that little is to be gained by assessing
      progression status any more frequently than would be required in routine clinical
      practice. Such design and analysis measures will optimize the development
      decision made at the end of phase II clinical evaluation.

PMID- 16807130
TI  - Minimization method for balancing continuous prognostic variables between
      treatment and control groups using Kullback-Leibler divergence.
AB  - This paper proposes a method for balancing prognostic variables between treatment
      and control groups in design of clinical trials. It assumes that some of
      prognostic variables are continuous and others are categorical and that they are
      independently distributed. The proposed method uses the Kullback-Leibler
      divergence (KLD) as the index of difference in distribution between two groups.
      It sequentially allocates each subject to a group using a biased coin method so
      as to reduce the estimate of KLD. That is, when first i subjects have been
      allocated to two groups and the (i+1)th subject is enrolled, the KLD is estimated
      if the (i+1)th subject was to be allocated to either of the groups, and the
      subject is then allocated with a certain probability, e.g. 0.80, so as to make
      the KLD small. Simulation studies based on the hypothetical prognostic variables
      and on the actual data of hyperlipidemia patients were carried out in order to
      compare the proposed method with the Pocock-Simon method, which transforms the
      continuous prognostic variables into categorical variables by dividing the whole
      scale into several categories. The p values of homogeneity test of means and
      variances were used to evaluate the achieved balance. The observed p values in
      the proposed method were better than those in the Pocock-Simon method. In
      addition to the balance, the precision of parameter estimates assuming analysis
      of covariance model was examined. The results showed the precision of estimators
      tended to be more stable in the proposed method than the Pocock-Simon method.

PMID- 16807131
TI  - Random-effects model for meta-analysis of clinical trials: an update.
AB  - The random-effects model is often used for meta-analysis of clinical studies. The
      method explicitly accounts for the heterogeneity of studies through a statistical
      parameter representing the inter-study variation. We discuss several iterative
      and non-iterative alternative methods for estimating the inter-study variance and
      hence the overall population treatment effect. We show that the leading methods
      for estimating the inter-study variance are special cases of a general method-of
      moments estimate of the inter-study variance. The general method suggests two new
      two-step methods. The iterative estimate is statistically optimal and it can be
      easily calculated on a spreadsheet program, such as Microsoft Excel, available on
      the desktop of most researchers. The two-step methods approximate the optimal
      iterative method better than the earlier one-step non-iterative methods.

PMID- 16807132
TI  - Cardiac autonomic function in chagasic elderly patients in an endemic area: A
      time and frequency domain analysis approach.
AB  - Chagas' disease is a common cause of cardiac autonomic impairment. In an endemic
      area there is a predominance of the indeterminate form and the number of elderly
      individuals committed by the disease is increasing. This study aimed to
      investigate the profile of heart rate variability (HRV) in elderly chagasic
      patients. 28 aged chagasic (CH), 28 non-chagasic (NC) aged individuals and 28
      adults between 20 and 40 years old (YG) were studied. R-R intervals were assessed
      in time and frequency domains applying an autoregressive algorithm. There was no
      difference regarding temporal and spectral indices among the elderly groups in
      baseline. The values of the variance in CH, NC and YG individuals were 891.80,
      283.60, 2557.00, showing a reduction of the total HRV in the aged groups when
      compared to the young control (p < 0.001). During the cold face test, the pNN50
      response was significantly different only in the young group (p < 0.001). The
      temporal and spectral indices were not different among the elderly groups. The
      percentile changes of the R-R intervals induced by the tilt test in CH, NC and YG
      were respectively -7.04%, -9.35%, -15.81%, being significantly higher in the
      young individuals (p < 0.001). There was no difference regarding the percentile
      changes of the temporal and spectral indices between CH and NC elderly patients.
      The cardiac autonomic function assessed by HRV parameters presented no
      differences among the elderly individuals (CH and NC) living in an endemic area.

PMID- 16807133
TI  - Surprising niche for the plant pathogen Pseudomonas syringae.
AB  - The biology and ecology of plant pathogenic bacteria have been studied almost
      exclusively in agricultural contexts. In contrast, for numerous human pathogens
      their biological activity in niches outside of medical contexts is well-known.
      Whereas there is increasing evidence that traits fostering survival in
      'environmental' niches can be the basis for virulence factors of human pathogens,
      niches for plant pathogenic bacteria outside of plants or of agricultural
      settings have not been elucidated. Most phytopathogenic bacteria are not obligate
      parasites, some of them can be transported to altitudes of several kilometres,
      they are scrubbed from the atmosphere by rainfall, and thus they are presumably
      transported to and might survive in a wide range of habitats. We isolated
      Pseudomonas syringae from river epilithon (rock-attached biofilms composed of
      algae, diatoms, rotifers, bacteria and nematodes) at densities up to 6000 cells
      g(-1) in France and the USA, some in pristine settings where waters flowed
      directly from snow melt and had not passed through agricultural zones. These
      strains induced hypersensitivity in indicator plants (tobacco) suggesting the
      presence of functional pathogenicity systems, and many induced disease in 1-7 of
      the plant species tested and produced a syringomycin-like toxin. Strains also
      were resistant to some antibiotics used to control plant diseases but not to
      copper sulphate. Sequencing of the 16S rDNA of epilithon strains and of reference
      strains of P. syringae revealed that a genetic lineage containing the strains
      with the broadest host range was distributed across several continents. Is it
      likely that wide spread dissemination of P. syringae occurs via aerosols and
      precipitation. This work highlights our limited understanding of non-agricultural
      niches in the ecology and evolution of plant pathogenic bacteria, of their role
      in the development of agricultural epidemics both as sources of inoculum and as
      sources of novel traits that may enhance bacterial pathogenicity and fitness.

PMID- 16807134
TI  - The effect of co- and superinfection on the adaptive dynamics of vesicular
      stomatitis virus.
AB  - In many infectious diseases, hosts are often simultaneously infected with several
      genotypes of the same pathogen. Much theoretical work has been done on modelling
      multiple infection dynamics, but empirical evidences are relatively scarce.
      Previous studies have demonstrated that coinfection allows faster adaptation than
      single infection in RNA viruses. Here, we use experimental populations of the
      vesicular stomatitis Indiana virus derived from an infectious cDNA, to show that
      superinfection dynamics promotes faster adaptation than single infection. In
      addition, we have analysed two different periodicities of multiple infection,
      daily and separated 5 days in time. Daily multiple infections allow higher
      fitness increases than multiple infections taking place every 5 days. We propose
      that the effect of superinfection on fitness is mainly influenced by the time
      elapsed between the first and the second infection, since shorter time intervals
      offer more opportunities to competition between resident and invading
      populations.

PMID- 16807135
TI  - Differential usage of non-homologous end-joining and homologous recombination in
      double strand break repair.
AB  - Repair of DNA double strand breaks (DSBs) plays a critical role in the
      maintenance of the genome. DSB arise frequently as a consequence of replication
      fork stalling and also due to the attack of exogenous agents. Repair of broken
      DNA is essential for survival. Two major pathways, homologous recombination (HR)
      and non-homologous end-joining (NHEJ) have evolved to deal with these lesions,
      and are conserved from yeast to vertebrates. Despite the conservation of these
      pathways, their relative contribution to DSB repair varies greatly between these
      two species. HR plays a dominant role in any DSB repair in yeast, whereas NHEJ
      significantly contributes to DSB repair in vertebrates. This active NHEJ requires
      a regulatory mechanism to choose HR or NHEJ in vertebrate cells. In this review,
      we illustrate how HR and NHEJ are differentially regulated depending on the phase
      of cell cycle and on the nature of the DSB.

PMID- 16807136
TI  - Palindromes and genomic stress fractures: bracing and repairing the damage.
AB  - DNA palindromes are a source of instability in eukaryotic genomes but remain
      under-investigated because they are difficult to study. Nonetheless, progress in
      the last year or so has begun to form a coherent picture of how DNA palindromes
      cause damage in eukaryotes and how this damage is opposed by cellular mechanisms.
      In yeast, the features of double strand DNA interruptions that appear at
      palindromic sites in vivo suggest that a resolvase-type activity creates the
      fractures by attacking a palindrome after it extrudes into a cruciform structure.
      Induction of DNA breaks in this fashion could be deterred through a Center-Break
      palindrome revision process as investigated in detail in mice. The MRX/MRN likely
      plays a pivotal role in prevention of palindrome-induced genome damage in
      eukaryotes.

PMID- 16807137
TI  - Transpositions and translocations induced by site-specific double-strand breaks
      in budding yeast.
AB  - Much of what we know about the molecular mechanisms of repairing a broken
      chromosome has come from the analysis of site-specific double-strand breaks
      (DSBs). Such DSBs can be generated by conditional expression of meganucleases
      such as HO or I-SceI or by the excision of a DNA transposable element. The
      synchronous creation of DSBs in nearly all cells of the population has made it
      possible to observe the progress of recombination by monitoring both the DNA
      itself and proteins that become associated with the recombining DNA. Both
      homologous recombination mechanisms and non-homologous end-joining (NHEJ)
      mechanisms of recombination have been defined by using these approaches. Here I
      focus on recombination events that lead to alterations of chromosome structure:
      transpositions, translocations, deletions, DNA fragment capture and other small
      insertions. These rearrangements can occur from ectopic gene conversions
      accompanied by crossing-over, break-induced replication, single-strand annealing
      or non-homologous end-joining.

PMID- 16807138
TI  - Analysis of mutagenic V(D)J recombinase mediated mutations at the HPRT locus as
      an in vivo model for studying rearrangements with leukemogenic potential in
      children.
AB  - Pediatric acute lymphocytic leukemia (ALL) is a multifactorial malignancy with
      many distinctive developmentally specific features that include age specific
      acquisition of deletions, insertions and chromosomal translocations. The analysis
      of breakpoint regions involved in these leukemogenic genomic rearrangements has
      provided evidence that many are the consequence of V(D)J recombinase mediated
      events at both immune and non-immune loci. Hence, the direct investigation of in
      vivo genetic and epigenetic features in human peripheral lymphocytes is necessary
      to fully understand the mechanisms responsible for the specificity and frequency
      of these leukemogenic non-immune V(D)J recombinase events. In this review, I will
      present the utility of analyzing mutagenic V(D)J recombinase mediated genomic
      rearrangements at the HPRT locus in humans as an in vivo model system for
      understanding the mechanisms responsible for leukemogenic genetic alterations
      observed in children with leukemia.

PMID- 16807139
TI  - Perspectives on the formation of radiation-induced exchange aberrations.
AB  - Controversy surrounding the proposed mechanism of radiation-induced translocation
      has existed virtually since the inception of radiation genetics/cytogenetics,
      some 75 years ago. Chief among these controversies is how close chromosomes have
      to be to one another at the time of exposure for an exchange to occur. An
      historically related issue, and one that continues to generate lively debate, is
      whether both chromosomes participating in an exchange must sustain radiation
      damage, or whether instead a single damaged site on one chromosome is sufficient.
      The intent of this paper is to present one person's perspective as we revisit
      these two long-standing issues, armed with more recent knowledge in three key
      areas. These include a new-found appreciation for the complexity of chromosome
      rearrangements; molecular processes of recombination that are likely to be
      involved; and the architecture of the nucleus regarding the relationship among
      chromosomes during interphase.

PMID- 16807141
TI  - Common fragile sites as targets for chromosome rearrangements.
AB  - Common fragile sites are large chromosomal regions that preferentially exhibit
      gaps or breaks after DNA synthesis is partially perturbed. Fragile site
      instability in cultured cells is well documented and includes gaps and breaks on
      metaphase chromosomes, translocation and deletions breakpoints, and sister
      chromosome exchanges. In recent years, much has been learned about the genomic
      structure at fragile sites and the cellular mechanisms that monitor their
      stability. The study of fragile sites has merged with that of cell cycle
      checkpoints and DNA repair, with multiple proteins from these pathways implicated
      in fragile site stability, including ATR, BRCA1, CHK1, and RAD51. Since their
      discovery, fragile sites have been implicated in constitutional and cancer
      chromosome rearrangements in vivo and recent studies suggest that common fragile
      sites may serve as markers of chromosome damage caused by replication stress
      during early tumorigenesis. Here we review the relationship of fragile sites to
      chromosome rearrangements, particularly in tumor cells, and discuss the
      mechanisms that may be involved.

PMID- 16807140
TI  - The involvement of non-B DNA structures in gross chromosomal rearrangements.
AB  - Non-B DNA conformations adopted by certain types of DNA sequences promote genetic
      instabilities, especially gross rearrangements including translocations. We
      conclude the following: (a) slipped (hairpin) structures, cruciforms, triplexes,
      tetraplexes and i-motifs, and left-handed Z-DNA are formed in chromosomes and
      elicit profound genetic consequences via recombination-repair, (b) repeating
      sequences, probably in their non-B conformations, cause gross genomic
      rearrangements (translocations, deletions, insertions, inversions, and
      duplications), and (c) these rearrangements are the genetic basis for numerous
      human diseases including polycystic kidney disease, adrenoleukodystrophy,
      follicular lymphomas, and spermatogenic failure.

PMID- 16807142
TI  - Open follow-up study of tobramycin nebuliser solution and colistin in patients
      with cystic fibrosis.
AB  - A previous study of tobramycin nebuliser solution (TNS) compared with colistin
      [C] in cystic fibrosis (CF) patients, chronically infected with pseudomonas,
      showed benefit for the TNS treated patients over one treatment cycle only. The
      current report is of an extension of that study. An open randomised cross-over
      study of TNS compared with C was conducted on 21 patients who had previously been
      on the 1 cycle study. They continued for a further 5 months and then crossed over
      to the alternate treatment. There was an advantage for TNS over C in FEV(1) %
      predicted change over time. The C slope was -0.88% per month and the TNS slope
      0.35% per month (p=0.0002). This suggests advantages of TNS over C in a study
      with a small number of patients. Larger studies are required.

PMID- 16807143
TI  - Comparison of methods of assessment of renal function in cystic fibrosis (CF)
      patients.
AB  - Renal failure is increasingly being recognised in CF patients, usually as a
      consequence of long-term nephrotoxic therapy. There is a need for a simple method
      of assessment of renal function in this patient group. We compared measured
      creatinine clearance from validated timed urine collections (the generally
      accepted practical test of glomerular filtration) with 10 formulae used to
      estimate creatinine clearance in a group of 74 CF adult patients and 29 matched
      normal controls. Compared to direct measurement, formulae gave a range of values
      (95% CI for mean bias -13 to +27.9 ml/min). Even those with the best correlation
      (r=0.7) gave wide error ranges (limits of agreement: -42.3 to 45.9 ml/min). The
      most commonly used formulae (Cockroft-Gault [CGF] and abbreviated Modification of
      Diet in Renal Disease [aMDRD]) were not superior to most other formulae tested.
      Both CGF and aMDRD-derived estimates compared less favourably in CF patients than
      controls (mean bias: 9.7 vs 3.4 ml/min (p<0.05) and 4.9 vs 1.4 (p<0.05)
      respectively; 78% vs 95% (p<0.01) and 77% vs 97% (p<0.01) of estimates within 33%
      of measurement respectively). In particular, both CGF and aMDRD grossly
      overestimated renal function (mean bias 18.3 and 15.8 ml/min respectively,
      p<0.001) in CF patients with reduced creatinine clearance (<80 ml/min). CGF,
      aMDRD and other formulae cannot be used to reliably assess renal function in CF
      patients, since they will fail to detect those with renal impairment. Some form
      of carefully supervised direct measurement is still required.

PMID- 16807145
TI  - Simultaneous determination of plasmatic phytosterols and cholesterol precursors
      using gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring
      (SIM).
AB  - Phytosterols (beta-sitosterol, cholestanol and campesterol) and cholesterol
      precursors (desmosterol and lathosterol), have been suggested as important
      biochemical markers of intestinal cholesterol absorption and liver biosynthesis,
      respectively, and as useful clinical parameters in the study of
      hypercholesterolemia, beta-sitosterolemia, atherosclerosis and cardiovascular
      disease, including pharmacological response to hypolipidemic agents. We developed
      an optimised analytical method for the simultaneous analysis of cholestanol,
      desmosterol, lathosterol, campesterol and beta-sitosterol in plasma using
      capillary gas chromatography coupled to mass spectrometry (GC-MS) with multiple
      selected ion monitoring (SIM). This method is based on the alkaline hydrolysis of
      sterol esters, extraction of free sterols and derivatization. The recovery of all
      sterols was in the range 76-101%. Within-day relative standard deviations
      (R.S.Ds.) and the between-day R.S.Ds. of cholestanol, desmosterol, lathosterol,
      campesterol and beta-sitosterol were less than 8%, and their plasma levels in 161
      normal subjects were (mean+/-S.D.) 4.73+/-2.57, 2.37+/-1.04, 6.23+/-3.14, 3.67+/
      1.95 and 5.92+/-3.62 micromol/l, respectively.

PMID- 16807146
TI  - Height and weight in Germany, evidence from the German Socio-Economic Panel,
      2002.
AB  - This paper examines the socio-economic variation in height and weight using data
      from the German Socio-Economic Panel. Results reinforce previous research insofar
      as height is associated with socio-economic differences. For example, a low
      maternal schooling level or a lower position in the income distribution is
      negatively correlated with the height of West Germans. Furthermore, there is a
      west-east and a north-south gradient in height in Germany. BMI is also determined
      by individuals' characteristics with similar underlying patterns. That is, in
      both West and East Germany, women with low income and low education have a higher
      BMI whereas the better educated women weigh less.

PMID- 16807147
TI  - Conformational stability of secretory leucocyte protease inhibitor: a protein
      with no hydrophobic core and very little secondary structure.
AB  - Conformational stability of proteins (including disulfide containing proteins)
      has been routinely characterized by spectroscopic techniques. Proteins which lack
      adequate signal of circular dichroism may require unconventional technique.
      Secretory Leucocyte Protease Inhibitor (SLPI) is a 107 amino acids protein with a
      high density of disulfide pairing (eight). The native SLPI has no hydrophobic
      core and contains very little hydrogen bonded secondary structure [Gruetter, M.,
      Fendrich, G., Huber, R., and Bode, W. (1988) The 2.5 A X-ray crystal structure of
      the acid stable proteinase inhibitor from human mucous secretions analyzed in its
      complex with bovine alpha-chymotrypsin. The EMBO J. 7, 345-352.]. In this study,
      conformational stability of SLPI has been investigated by the method of disulfide
      scrambling, which permits quantification of the native and denatured (scrambled)
      proteins by HPLC. Due to high heterogeneity of denatured SLPI, the native and
      scrambled SLPI are extensively overlapped on HPLC. This impediment was further
      overcome by the development of a novel method which distinguishes the native and
      scrambled isomers of SLPI by exploiting the relative stability of their disulfide
      bonds. The study reveals mid-point denaturation of SLPI at 1.36 M of GdmSCN, 4.0
      M of GdmCl and >8 M urea. Based on the GdmCl denaturation curve, the unfolding
      free energy (DeltaG(H20)) of SLPI was estimated to be 4.56 kcal/mol. The results
      of our studies suggest an alternative strategy for analyzing conformational
      stability of disulfide proteins that are not suitable to the conventional
      spectroscopic techniques.

PMID- 16807148
TI  - On the statistical analysis of the GS-NS0 cell proteome: imputation, clustering
      and variability testing.
AB  - We have undertaken two-dimensional gel electrophoresis proteomic profiling on a
      series of cell lines with different recombinant antibody production rates. Due to
      the nature of gel-based experiments not all protein spots are detected across all
      samples in an experiment, and hence datasets are invariably incomplete. New
      approaches are therefore required for the analysis of such graduated datasets. We
      approached this problem in two ways. Firstly, we applied a missing value
      imputation technique to calculate missing data points. Secondly, we combined a
      singular value decomposition based hierarchical clustering with the expression
      variability test to identify protein spots whose expression correlates with
      increased antibody production. The results have shown that while imputation of
      missing data was a useful method to improve the statistical analysis of such data
      sets, this was of limited use in differentiating between the samples
      investigated, and highlighted a small number of candidate proteins for further
      investigation.

PMID- 16807149
TI  - Collagenous pouchitis.
AB  - Collagenous colitis is characterised by watery diarrhoea, normal colonic mucosa
      on endoscopy, diffuse colitis with surface epithelial injury, and a distinctive
      thickening of the subepithelial collagen table on histology. Some patients can
      develop medically refractory collagenous colitis, in which case they may require
      surgical intervention. This is the first report of collagenous pouchitis in a
      collagenous colitis patient with proctocolectomy and ileal pouch-anal
      anastomosis. A patient with medically refractory collagenous colitis who
      underwent a total proctocolectomy and ileal pouch-anal anastomosis was
      sequentially evaluated with an endoscopy and histology of the colon, distal small
      intestine, and ileal pouch. A 58-year-old female had a 10-year history of
      collagenous colitis before having a total proctocolectomy and ileal pouch-anal
      anastomosis for medically refractory disease. The histologic features of
      collagenous colitis were present in all colon and rectum biopsy or resection
      specimens, but were absent in the distal ileum specimen. The post-operative
      course was complicated by persistent increase of stool frequency, abdominal
      cramps, and incontinence. A pouch endoscopy was performed 3 years after ileal
      pouch-anal anastomosis which showed the histologic features of collagenous
      colitis in the ileal pouch, collagenous pouchitis, while the pre-pouch neo
      terminal ileum had no pathologic changes. After antibiotic therapy, the
      histologic changes of collagenous pouchitis resolved. This is the first reported
      case of collagenous pouchitis. Since the abnormal collagen table and its
      associated features were only present in the pouch and absent in the neo-terminal
      ileum, and the patient had histologic improvement after antibiotic therapy, it
      would suggest that faecal stasis and bacterial load may play a role in the
      pathogenesis.

PMID- 16807151
TI  - Optical coherence tomography compared with histology of the main pancreatic duct
      structure in normal and pathological conditions: an 'ex vivo study'.
AB  - BACKGROUND AND STUDY AIMS: Optical coherence tomography permits high-resolution
      imaging of tissue microstructures by a probe inserted into the main pancreatic
      duct through a standard ERCP catheter. The aim of this study was to compare
      optical coherence tomography images of the main pancreatic duct with histology
      and identify the optical coherence tomography pattern of the normal and
      pathological structure of the main pancreatic duct. PATIENTS AND METHODS:
      Multiple sections of neoplastic and non-neoplastic segments of 10 consecutive
      surgical pancreatic specimens obtained from patients with pancreatic head
      adenocarcinoma were investigated by optical coherence tomography scanning within
      1h of resection. One hundred optical coherence tomography findings were then
      compared with the corresponding histopathological diagnoses. RESULTS: Main
      pancreatic duct wall architecture appeared at optical coherence tomography
      investigation as a three-layer structure with a different back-scattered signal
      from each layer. Optical coherence tomography imaging was concordant with
      histology in 81.8% and 18.75% of sections with normal tissue and chronic
      inflammatory changes. The K statistic between the two procedures was equal to
      0.059 for non-neoplastic main pancreatic duct wall appearance. In all neoplastic
      sections optical coherence tomography showed a subverted layer architecture with
      heterogeneous back-scattering of the signal and was concordant with histology.
      CONCLUSIONS: Optical coherence tomography provided images of main pancreatic duct
      wall structure that were concordant with histology in 100% of cases in presence
      of neoplastic ductal changes and did not have false-positive or negative results.
      Optical coherence tomography images were also concordant with histology in about
      80% of cases with normal main pancreatic duct structure; however, the
      differential diagnosis between normal tissue and chronic pancreatitis or
      dysplastic changes appeared very difficult.

PMID- 16807150
TI  - Characterization of gene expression profile in rat Kupffer cells stimulated with
      IFN-alpha or IFN-gamma.
AB  - BACKGROUND AND AIM: Kupffer cells are intrasinusoidal space located macrophages
      with phagocytic capacity. Interferons are cytokines with antiviral,
      antiproliferative and immunomodulatory activities which may influence the
      activity of Kupffer cells. Aim of this study was to evaluate Kupffer cell gene
      expression after interferon-alpha or interferon-gamma stimulation in order to
      investigate a link between these cytokines and macrophage activation. METHODS:
      Rat Kupffer cells were cultured for 24 h and divided into three groups:
      unstimulated; stimulated with interferon-alpha and stimulated with interferon
      gamma. After 8 h stimulation total RNA was extracted and processed according to
      Affymetrix protocols and hybridised on R34A microarray gene set. Data analyses
      was performed using Microarray Analysis Suite 5.0 software. Genes showing
      remarkably different expression in microarray analysis were confirmed by real
      time PCR. RESULTS: Nearly 4000 out of the 8800 genes represented in the array
      were expressed by Kupffer cells. Among these, interferon-alpha up-regulates 91
      genes by over two-fold (antiviral, antigen processing and presentation, and
      tumour suppressor/proapoptotic genes) and down-regulates 72 genes by 50% or more.
      Interferon-gamma up-regulates 70 genes by over two-fold and down-regulates 78
      genes by 50% or more. Most of the genes induced by interferon-alpha are also
      induced by interferon-gamma. Down-regulated genes include growth factors and
      genes involved in cell cycle/proliferation. Real-time PCR confirms the results of
      the array. CONCLUSION: Interferons directly target rat Kupffer cells and are
      involved in the regulation of a wide variety of genes. Their expression profile
      shed light onto molecular mechanism of Kupffer cells activation in specific
      pathways such as antiviral and antitumour processes.

PMID- 16807152
TI  - Expressional analysis of anti-apoptotic phospho-BAD protein and mutational
      analysis of pro-apoptotic BAD gene in hepatocellular carcinomas.
AB  - BACKGROUND: It has become clear that, together with proliferation, deregulation
      of apoptosis plays a pivotal role in tumourigenesis. BAD is a pro-apoptotic Bcl-2
      family protein and regulates the intrinsic apoptosis pathway. Phosphorylation of
      BAD inhibits the apoptosis function of BAD. AIMS: To investigate whether
      alteration of the phospho-BAD protein and somatic mutation of BAD gene are
      characteristics of human hepatocellular carcinoma. PATIENTS AND METHODS: We
      analysed the expression of phospho-BAD in 20 hepatocellular carcinomas by
      immunohistochemistry. Also, we analysed the BAD gene for the detection of somatic
      mutations by a single-strand conformation polymorphism assay in 69 hepatocellular
      carcinomas. RESULTS: Phospho-BAD expression in the non-tumour hepatocytes was
      seen in all of the hepatocellular carcinomas, while the expression in the cancer
      cells was observed in 15% (3 of the 20) of the hepatocellular carcinomas. There
      was no somatic mutation of BAD Bcl-2 homology 3 (BH3) domain in the 69
      hepatocellular carcinomas. CONCLUSIONS: The data showed that loss of phospho-BAD
      expression, but not BAD gene mutation, is a feature of hepatocellular carcinomas.
      The decreased expression of phospho-BAD in the hepatocellular carcinoma cells
      compared to the non-tumour hepatocytes suggests that loss of phospho-BAD
      expression may play a role in hepatocellular tumourigenesis.

PMID- 16807154
TI  - Irritable bowel syndrome: the burden and unmet needs in Europe.
AB  - Irritable bowel syndrome affects approximately 10-15% of the European population,
      although prevalence rates vary depending on the classification used and the
      country surveyed. This may be due to differences in patterns of medical care and
      diagnosis of the condition. Up to 70% of individuals with irritable bowel
      syndrome may not have been formally diagnosed. The disorder affects 1.5-3 times
      as many women as men and poses a significant economic burden in Europe, estimated
      at euro 700-euro 1600 per person per year. It also reduces quality of life and is
      associated with psychological distress, disturbed work and sleep, and sexual
      dysfunction. It is a chronic disorder, which affects many individuals for more
      than 10 years. Most patients are managed in primary care, although some are
      referred to gastroenterologists and other specialists. Patients with irritable
      bowel syndrome undergo more abdomino-pelvic surgery than the general population.
      We propose that a positive diagnosis of the condition may avoid the delay in
      diagnosis many patients experience. We conclude that, in Europe, there are
      significant unmet needs including lack of familiarity with irritable bowel
      syndrome, difficulties in diagnosis and lack of effective treatments for the
      multiple symptoms of the disorder. The development of pan-European guidelines for
      irritable bowel syndrome will benefit patients with this condition in Europe.

PMID- 16807156
TI  - Fibre reinforced bioresorbable composites for spinal surgery.
AB  - Composites containing different amounts of beta-tricalcium phosphate (beta-TCP)
      embedded in a poly-lactide (PLA70) matrix with and without poly-lactide (PLA96)
      fibre reinforcement were studied and the feasibility of using these composites in
      spinal fusion implants was examined. Compressive yield strength was measured in
      two directions: parallel to (83-97 MPa) and perpendicular to (108-123 MPa) the
      laminated structure of the composites. In the parallel direction, the addition of
      beta-TCP decreased compressive yield strength while in the perpendicular
      direction this was increased when compared to plain specimens (p<0.05). Fibre
      reinforcement had no significant effect on compressive yield strength (p<0.05),
      but did increase impact strength by 127-216% for notched specimens (parallel
      direction) and by about 65% for un-notched specimens (perpendicular direction)
      (p<0.05). A 24 week in vitro analysis of implant prototypes in simulated body
      fluid revealed a decrease in compressive yield strength, which was greater for
      the samples containing 50 wt.% beta-TCP than for those containing 25 wt.% beta
      TCP. After 12 weeks incubation the composites retained 66-99% of their initial
      compressive strength, depending on composition. After 24 weeks incubation the
      lowest compressive strength was 51% (56 MPa: 50/50) and the highest was 94% (90
      MPa: 75/25) of the initial value. Calcium phosphate precipitation on the surfaces
      of the materials in vitro was also observed. The initial compressive strengths of
      the studied composites were comparable to materials used in spinal fusion
      applications, but adequate strength retention behaviour needs to be confirmed
      before undertaking clinical experiments.

PMID- 16807157
TI  - Danger: hydra in wonderland!

PMID- 16807158
TI  - A new case of megalencephaly and perisylvian polymicrogyria with post-axial
      polydactyly and hydrocephalus: MPPH syndrome.
AB  - We report a new case of megalencephaly and polymicrogyria with post-axial
      polydactyly and hydrocephalus (MPPH syndrome) in an 18-month-old girl. She was
      the first child of healthy non-consanguineous parents and measurements at birth
      were +3 standard deviations (S.D.) for weight, +2 S.D. for length and +4 S.D. for
      OFC. Ultrasound scan at 24 weeks of gestation (WG) showed mild ventriculomagaly
      with unique umbilical artery and dacryocystocele. Clinical examination at birth
      revealed macrosomia with macrocephaly, facial dysmorphism, post-axial polydactyly
      at the right hand and both feet, and axial hypotonia with hypertonic arms and
      legs. At 18 months of age, weight was +2 S.D., length was +2 S.D. and OFC was +4
      S.D. She remained hypertonic, could not sit and had no hand use. Cerebral
      magnetic resonance imaging showed stable ventriculomegaly and polymicrogyria
      located on the frontal and perisylvian region with white matter hypersignal on T2
      weighted images. There was no associated visceral malformation. Standard and high
      resolution cytogenetic examination, telomeric FISH and array-CGH studies were
      normal. This case represents the sixth observation of MPPH syndrome as described
      by Mirzaa et al. in 2004. We provide further neurological follow-up since three
      out of five index patients were aged 6 months or less. We postulate that
      macrosomia at birth might be a major feature (five/six cases), with advanced bone
      age in the two/two investigated cases. White matter abnormalities might be an
      occasional feature of this syndrome (three/six cases), as well as
      dacryocystocele, if not coincidental (one/six case). The mode of inheritance of
      this syndrome remains unknown since there was no significant family history in
      all reported cases. The search for infracytogenetic chromosomal imbalance was
      unsuccessful.

PMID- 16807160
TI  - The learning processes of international students through the eyes of foreign
      supervisors.
AB  - Semi-structured interviews were conducted with external supervisors of
      international electives undertaken by Dutch undergraduate students, in order to
      gain insight into student learning processes during these electives. The
      interviews served to triangulate information on these learning processes that was
      obtained from students' self-reports. The results of the case study reported in
      this paper were largely consistent with findings from prior studies of
      international electives in which learning processes and sociocultural differences
      were examined: experiential learning processes appeared to dominate and
      sociocultural differences occasionally seemed to blur productive learning,
      especially when the differences between the national cultures of host country and
      student home country were substantial. It is recommended that students'
      experiential learning from international electives should be supplemented with
      'guided' and 'self-directed' learning with a focus on the sociocultural
      dimension.

PMID- 16807159
TI  - Bisphosphonates suppress periosteal osteoblast activity independently of
      resorption in rat femur and tibia.
AB  - Recent studies demonstrate that bisphosphonates suppress bone resorption by
      leading to apoptosis of the osteoclast and inhibiting the differentiation to
      mature osteoclasts. The influence of bisphosphonates on bone formation is
      unknown, although it has been hypothesized that bisphosphonates inhibit
      osteoblast apoptosis and stimulate osteoblast proliferation and differentiation
      in vitro, leading to increased bone formation. The purpose of this study was to
      investigate the effect of bisphosphonates on bone formation. We administered
      risedronate at 0.05, 0.5 or 5.0 microg/kg/day or alendronate at 0.1, 1.0 or 10
      microg/kg/day subcutaneously for 17 days to 6-month-old female Sprague-Dawley
      rats. Control rats were given a daily subcutaneous injection of saline. Following
      sacrifice, the femoral and tibial mid-diaphyses were harvested and mineralizing
      surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR/BS)
      were measured on periosteal and endocortical surfaces. In the femur, periosteal
      MAR was significantly lower in all treatment groups (22-29% for risedronate, 26
      36% for alendronate) than in control. In the tibia, periosteal MAR and BFR of all
      treatment groups were significantly lower (41-50% for risedronate, 43-52% for
      alendronate) than in the control group. Because the periosteal surfaces of these
      bones are only undergoing bone formation in modeling mode, our results show that
      bisphosphonates suppress bone formation independently of bone resorption. Because
      this effect is seen on periosteal MAR rather than on periosteal MS/BS, we
      hypothesize that bisphosphonates affect the activity of individual osteoblasts at
      the cell level. This may help to explain the reason that the anabolic effects of
      teriparatide are blunted when administered concurrently with or following a
      course of bisphosphonates in humans.

PMID- 16807161
TI  - Effect of teaching context and tutor workshop on tutorial skills.
AB  - Effective faculty development workshops are essential to develop and sustain the
      quality of faculty's teaching. In an integrated problem-based curriculum, tutors
      expressed the needs to further develop their skills in facilitating students'
      content learning and small-group functioning. Based on the authors' prior
      observations that tutors' performance depends on their teaching context, a
      workshop was designed not only tailored to the tutors' needs but also organized
      within their respective teaching unit. The purposes of this study are (1) to
      evaluate whether this workshop is effective and improves tutors' teaching skills,
      and (2) to assess whether workshop effectiveness depends on tutors' performance
      before the workshop and on their teaching unit environment. Workshop
      effectiveness was assessed using (a) tutors' perception of workshop usefulness
      and of their improvement in tutorial skills, and (b) students' ratings of tutor
      performance before and after the workshop. In addition, an analysis of variance
      model was designed to analyse how tutors' performance before the workshop and
      their teaching unit influence workshop effectiveness. Tutors judged the workshop
      as helpful in providing them with new teaching strategies and reported having
      improved their tutorial skills. Workshop attendance enhanced students' ratings of
      tutors' knowledge of problem content and ability to guide their learning. This
      improvement was also long-lasting. The workshop effect on tutor performance was
      relative: it varied across teaching units and was higher for tutors with low
      scores before the workshop. A workshop tailored to tutors' needs and adapted to
      their teaching unit improves their tutorial skills. Its effectiveness is,
      however, influenced by tutors' level of performance before the workshop and by
      the environment of their teaching unit. Thus, to be efficient, the design of a
      workshop should consider not only individual tutors' needs, but also the
      background of their teaching units, with special attention to their internal
      organization and tutor group functioning.

PMID- 16807162
TI  - An expert patient-led approach to learning and teaching: the case of
      physiotherapy.
AB  - With patient expertise being afforded greater legitimacy in healthcare provision,
      there is a strengthening case for involving patients more creatively in the
      education of healthcare professionals. This paper reports on the results of a
      small-scale educational research project designed to explore how third-year
      physiotherapy students experienced a teaching session on the subject of strokes,
      led by two expert patients, and what they learnt from it. Applying a qualitative
      methodology, six students were interviewed in depth about the experience. Four
      key pedagogic themes emerged from the analysis of the interview transcripts. The
      first related to the differences between the expert patients in terms of their
      backgrounds and their reactions to experiencing a stroke and of their respective
      contributions to the session. A second concerned the anxieties students felt in
      participating in a session of this kind, since there were various departures from
      the norm, and what they should take from it in terms of their learning. A third
      theme was uncertainty regarding the relationship between the presenters and
      students. The fourth theme was the impact on student learning given that it had
      not been a conventional session. Notwithstanding any misgivings the session
      helped to validate the contribution that those who have direct experience of a
      clinical condition can make to the education of healthcare professionals,
      particularly in the affective domain. In planning sessions of this kind it is
      recommended that presenters are chosen with a view to challenging stereotypes and
      that they are encouraged to tell their stories in an open and flexible manner,
      albeit within a framework of intended learning outcomes. Students need to
      approach the session with an open mind and, above all, tutors need to be prepared
      to take risks.

PMID- 16807164
TI  - The small group in problem-based learning: more than a cognitive 'learning'
      experience for first-year medical students in a diverse population.
AB  - In problem-based learning (PBL) curricula, first-year students need to adapt to a
      new learning environment and an unfamiliar new pedagogy. The small-group tutorial
      potentially offers a learning environment where students can become self-directed
      learners, collaborating with other group members to achieve individual and group
      learning goals. At the end of the first six-week theme in a relatively new PBL
      curriculum, new medical students were canvassed about coping with PBL (self
      directed learning; content; time management; resources) and the value of the
      small-group tutorial, the latter of which is currently being reported. Almost 84%
      of students (n = 178) responded. The benefits of participating in small groups
      were categorized into three domains-cognitive, affective and social-as identified
      from student responses. Results were analysed in terms of gender and prior
      educational experience (secondary school vs. prior tertiary educational
      experience). For almost 94% of students, the small-group tutorial provided a
      conducive learning environment that influenced their personal development (i.e.
      tolerance, patience) and socialization into the faculty. Significantly more males
      indicated that they had developed social skills, while more school-leavers
      (matriculants) than mature students felt more receptive to the views of others.
      More mature students claimed to have made friends. Irrespective of some
      conflicting opinions in the literature, the present results suggest that the PBL
      tutorial may be important in facilitating student socialization into a new and
      unfamiliar academic environment, particularly when the pedagogy differs markedly
      from their past educational experiences. Through interacting with fellow students
      from diverse origins who hold different views in the intimate setting of the
      small group, students felt that they had not only increased their knowledge but
      had also developed personally and socially. It is proposed that the small group
      may be useful for integrating a diverse population of students into a new
      academic environment.

PMID- 16807165
TI  - What is EBM and how should we teach it?

PMID- 16807166
TI  - A matter of explanation: assessment, scholarship of teaching and their disconnect
      with theoretical development.
AB  - This commentary explores the development of assessment and its implications on
      the scholarship of teaching. Assessment and the scholarship of teaching's aim has
      been fixed on the practical and relevant, rarely furthering what we collectively
      know about student learning and development. As medical educators investigate
      important educational issues, informing assessment efforts with existing
      literature and a theoretical framework offers several advantages. Aligning sound
      assessment plans with a theoretical framework not only addresses essential
      questions about the extent students are learning, but provides direction, focus
      and coordination for future investigations.

PMID- 16807167
TI  - Developing a learning culture: twelve tips for individuals, teams and
      organizations.
AB  - A culture of learning in providing health services and education for health
      professionals is a constant challenge for individuals, team and organizations.
      The importance of such a culture was highlighted by the findings of the Bristol
      Royal Infirmary Inquiry (2001). This was discussed in the context of the
      literature on the Learning Organization (Senge, 1990) at the 2004 Association of
      Medical Education in Europe (AMEE) conference, and reviewed a year later at the
      2005 AMEE conference. This paper outlines twelve tips for educational and health
      service organizations in facilitating a culture of learning for their members and
      also offers specific advice to individual students and professionals.

PMID- 16807168
TI  - Teaching evidence-based medicine to undergraduate medical students: a course
      integrating ethics, audit, management and clinical epidemiology.
AB  - A six-week full time course for third-year undergraduate medical students at
      Imperial College uniquely links evidence-based medicine (EBM) with ethics and the
      management of change in health services. It is mounted jointly by the Medical and
      Business Schools and features an experiential approach. Small teams of students
      use a problem-based strategy to address practical issues identified from a range
      of clinical placements in primary and secondary care settings. The majority of
      these junior clinical students achieve important objectives for learning about
      teamwork, critical appraisal, applied ethics and health care organisations. Their
      work often influences the care received by patients in the host clinical units.
      We discuss the strengths of the course in relation to other accounts of
      programmes in EBM. We give examples of recurring experiences from successive
      cohorts and discuss assessment issues and how our multi-phasic evaluation informs
      evolution of the course and the potential for future developments.

PMID- 16807169
TI  - Evidence-based medicine: discrepancy between perceived competence and actual
      performance among graduating medical students.
AB  - Since at the time of graduation from medical school physicians are expected to
      demonstrate adequate professional competence including mastery of critical
      appraisal skills, we conducted a preliminary, cross-sectional, web-based study to
      examine the extent to which fourth year medical students in the US are competent
      in core areas of evidence-based medicine (EBM). Using self-assessment
      instruments, subjects (n = 150) were asked to demonstrate their ability to
      understand the practical meaning of key methodological and data analysis
      constructs as they relate to patient care, to rate their perceived competence in
      core areas of EBM and to disclose their attitudes toward critical appraisal of
      the literature and EBM. The mean score in our cohort was 55% suggesting that
      students may have knowledge gaps that interfere with their ability to critically
      appraise the medical literature. There was an apparent chasm between subjects'
      perceived competence and their actual performance on the assessment instrument.
      These findings, if corroborated in larger studies, (1) suggest that better
      education in EBM is needed so as to avoid the possibility that patient care may
      inadvertently be jeopardized; and (2) cast doubt on the use of self-assessed
      knowledge as a proxy for actual skills with respect to EBM and medical decision
      making.

PMID- 16807170
TI  - The assessment and treatment of the acutely ill patient--the role of the patient
      simulator as a teaching tool in the undergraduate programme.
AB  - The assessment and treatment of the acutely ill patient is an essential part of
      the role of the pre-registration house officer, and research has demonstrated
      that management of such patients in the ward setting is often sub-optimal.
      However, this is an area which is difficult to teach at an undergraduate level,
      particularly without exposing patients to unnecessary risk. A patient simulator
      such as the SimMan could allow these issues to be addressed in a safe,
      reproducible and controlled environment. A protocol for the assessment and
      treatment of the acutely ill patient was designed. This was then implemented
      using a series of three teaching sessions during which small groups of final year
      medical students took part in simulated clinical scenarios on the SimMan
      mannequin. A questionnaire was administered to participating students before and
      after teaching to assess their perceived confidence and competence in a number of
      areas deemed important for newly qualified house officers. Data from 23 students
      were obtained and demonstrated a significant improvement in students' perceived
      levels of confidence and competence following training on the simulator. Feedback
      from students was extremely positive with all students reporting that sessions
      were a valuable addition to the final year programme. The SimMan allows students
      to gain knowledge and skills in a vital area of clinical practice which hitherto
      had been poorly covered within the curriculum. The sessions will be incorporated
      into the teaching programme for all future final-year students.

PMID- 16807171
TI  - Can a ward simulation exercise achieve the realism that reflects the complexity
      of everyday practice junior doctors encounter?
AB  - Recent changes in medical education have resulted in an increased focus on
      patient safety. It is vital that new doctors can recognize and manage acutely-ill
      patients, as well as work safely and effectively as a member of a multi
      professional team. A ward simulation exercise has been developed to provide a
      safe, but authentic setting to support junior doctors with further practice and
      feedback. In developing such an exercise realism is important in recreating the
      complex climate in which the junior doctor has to function as part of the
      healthcare team in the hospital ward. This paper shares the design methodology of
      a ward simulation exercise and the views on its authenticity from both the junior
      doctors and the observers.

PMID- 16807172
TI  - The effectiveness of academic admission interviews: an exploratory meta-analysis.
AB  - Admission to health-related professions is very competitive and selecting
      candidates with the best prospects for success is critical. A variety of measures
      are used to assess candidates to predict success. The purpose of this research
      was to assess the effectiveness of using selection interviews for admissions.
      Meta-analysis was applied to a sample of 20 studies examined in a comprehensive
      review article on the use of interviews in healthcare academic disciplines.
      Nineteen of these studies examined the relationship between performance in an
      interview situation and academic performance, while 10 examined the relationship
      between performance in an interview situation and clinical performance. A
      separate meta-analysis was conducted for each category of performance measure.
      The mean sample-size-effect size for studies examining the predictive power of
      interviews for academic success was 0.06 (95% confidence intervals 0.03-0.08),
      indicating a very small effect. The sample of studies was homogeneous using a
      fixed-effect model. The sample of studies for predicting clinical success had a
      mean effect size of 0.17 (95% confidence intervals 0.11-0.22), indicating modest
      positive predictive power. Using a random-effects model, this sample of studies
      was also homogeneous. Future research should investigate a larger sample of
      primary studies.

PMID- 16807173
TI  - Nursing faculty teaching basic skills to medical students.
AB  - Medical education often uses a 'see one, do one, teach one' approach to teaching
      basic skills, whereas nursing education uses a more intense, competency based
      approach. Many nursing faculty become experts in teaching skills; however, there
      is little literature evaluating medical student skills training led by nursing
      faculty. The purpose of this paper is to describe and report initial evaluation
      data on an innovative teaching strategy using nursing faculty to teach specific
      skills to medical students. Nursing faculty designed a hands-on four hour
      clinical skills training laboratory for medical students. All (176) medical
      students completed and evaluated this skills laboratory and their own preparation
      for these skills. Medical students felt the laboratory was outstanding or good
      (94%), the content was at an appropriate level (94%) and the relevance was high
      or medium (96%). Medical students felt more prepared to perform the skills after
      completing the skills laboratory than before, and when compared to previous
      medical students without the skills laboratory. Many medical students commented
      positively about the nursing faculty. Nursing faculty teaching specific skills to
      medical students is acceptable and effective and provides medical students with
      positive exposure to nurses as experts.

PMID- 16807174
TI  - Tuning medical education for rural-ready practice: designing and resourcing
      optimally.
AB  - In an effort to bring doctors back to the bush the Australian government has
      resourced a number of rural clinical schools (RCS). At the RCS in the University
      of Western Australia students were allocated in small groups to rural sites for
      the entire fifth year of a six-year course, sitting the same final examinations
      as city students. Key factors guiding the successful outcome were the resourcing
      and implementation of the infrastructure and teaching and learning pedagogy. In
      designing support, the disconnection of students from their city colleagues was
      anticipated as an issue, as was the pedagogical indoctrination of the teachers.
      The curriculum implementation was adapted in this light. The role of the Web in
      teaching and learning, and their status as 'student colleagues' and independent
      learners were pivotal aspects. As students settled at their site, their
      confidence grew and their anxiety over urban disconnection dissipated. By
      benchmarking themselves using Web-based formative assessments and in formative
      'objective structured clinical examinations' staged for them by the RCS, the
      students received ongoing feedback on their progress. This model of embedding
      students in rural centres for an extended period with rural practitioners as
      teachers was successfully implemented at multiple sites geographically vastly
      separate.

PMID- 16807175
TI  - Medical education in the public versus the private setting: a qualitative study
      of medical students' attitudes.
AB  - Public hospitals serve as primary training sites for medical students. Public
      patients may therefore bear a disproportionate burden of medical student
      education. The purpose of this study was to critically examine the ethics of
      medical education in the public setting. Attitudes of first- and fourth-year
      students towards the role of public patients in medical education were elicited
      in focus groups. Inductive qualitative analysis was utilized to organize data
      into conceptual groups, which were then analyzed within an ethical framework. All
      patients have an equal obligation to participate in medical education. Students
      identified modifying factors that could affect a patient's obligation to educate
      future physicians. Available data highlight a concern that public teaching
      hospitals may provide a lower quality of care. If true, then the public teaching
      setting is creating an unfair burden upon that patient population who would then
      have a weakened obligation to participate in medical education.

PMID- 16807176
TI  - Use of portfolios as a learning and assessment tool in a surgical practical
      session of urology during undergraduate medical training.
AB  - We chose to introduce a portfolio as a learning and assessment tool in a
      practical training session of urological surgery for undergraduate medical
      students. Our primary objectives were to develop the students' self reflexive
      ability in front of complex medical cases and to teach them how to identify their
      learning needs in a short period of time, on a specific topic. Students
      completed, during their training session, a portfolio on a urological topic under
      the constant supervision of a tutor. The students were evaluated on their
      portfolio's presentation with a 20-point grade grid known in advance. Even in a
      surgical training session, a portfolio can be a useful learning and assessment
      tool. It clearly encourages self-reflection and pre-professional practice.

PMID- 16807177
TI  - The oral board examination for plastic surgery: seeking a better way.
AB  - Passing written and oral certifying examinations is a prerequisite to obtaining
      the license required from the Ministry of Health to start practicing as a Plastic
      Surgeon in Israel. In recent years, residents have complained about the
      unfairness of the method of the oral examination in terms of questions that
      varied according to the examiner. Before instituting changes, the position and
      attitudes of plastic surgeons in Israel, both senior surgeons and residents,
      regarding the oral examination was investigated. A detailed questionnaire
      containing 20 questions was distributed among 44 senior surgeons and 17 residents
      who attended the Annual Meeting of Israeli Plastic and Reconstructive Surgery
      Association in November 2001. The answers were analysed using the Pearson chi
      square test. According to this survey, a majority of responders agreed that the
      format of the oral examination should be changed. Although significant
      differences were found among the senior surgeons and the residents, the approach
      of the residents was found to be more acceptable. Reflecting the literature, the
      residents felt that the oral examination should be built of standardized
      questions and the anticipated answers should be pre-determined. The examination
      should cover a wide spectrum of subjects, with a restricted amount of time for
      each answer. A majority, 77% of the seniors and 64% of the residents, agreed that
      there was something to be learned about the abilities of the examinee from the
      presentation of a few case studies, and it was felt that this should be added to
      the revised examination. Only competent examiners should participate and each
      should rate the examinee independently. An observer from the same program was
      preferred. The majority of the responders also preferred a high quality and valid
      examination and did not like to view the examination as a barrier to entering the
      profession.

PMID- 16807178
TI  - Graduating internal medicine residents' self-assessment and performance of
      advanced cardiac life support skills.
AB  - Internal medicine residents in the US must be competent to perform procedures
      including Advanced Cardiac Life Support (ACLS) to become board-eligible. Our aim
      was to determine if residents near graduation could assess their skills in ACLS
      procedures accurately. Participants were 40 residents in a university-based
      training program. Self-assessments of confidence in managing six ACLS scenarios
      were measured on a 0 (very low) to 100 (very high) scale. These were compared to
      reliable observational ratings of residents' performance on a high-fidelity
      simulator using published treatment protocols. Residents expressed strong self
      confidence about managing the scenarios. Residents' simulator performance varied
      widely (range from 45% to 94%). Self-confidence assessments correlated poorly
      with performance (median r = 0.075). Self-assessment of performance by graduating
      internal medicine residents was not accurate in this study. The use of self
      assessment to document resident competence in procedures such as ACLS is not a
      proxy for objective evaluation.

PMID- 16807179
TI  - Measuring wellness among resident physicians.
AB  - Requirements to include professionalism in residency curricula have generated a
      substantial body of literature concerning the environments that fail to nurture
      professionalism. Local and national surveys provide evidence that a high
      prevalence of depersonalization and emotional exhaustion exists among residents
      and that clinical practice is impaired as a result of these factors. A group of
      34 residents from ten residency programmes participated in the psychometric
      testing of a resident wellness assessment instrument that can be rapidly
      administered, scored, and interpreted. The Brief Resident Wellness Profile is
      composed of a Mood faces graphical rating item and a six-question subscale. The
      six-item subscale had good reliability (alpha = 0.83; r = 0.84), convergent
      validity (r = 0.63), discriminant validity (r = -0.37), and concurrent validity (
      p = 0.007). The Mood faces item had good convergent validity (r = 0.66),
      discriminant validity (r = -0.71), and concurrent validity ( p = 0.008). The
      Brief Resident Wellness Profile appears to be a reliable and valid instrument
      that measures residents' sense of professional accomplishment and mood and can be
      rapidly administered, scored, and interpreted.

PMID- 16807180
TI  - Study guides: a study of different formats.
AB  - More emphasis is being placed on students as independent learners with teachers
      acting as facilitators. It has been argued that student-centred learning can be
      supported usefully by study guides. This paper supports previous claims as to the
      value of study guides as perceived by students. But what should study guides look
      like? A total of 151 second-year medical students at the University of Dundee
      were given three versions of a study guide covering the topic of hypertension,
      each incorporating a different educational approach but with the same content. A
      timetable-based version of the guide focused on the students' day-to-day
      timetable and related the learning outcomes to each of the scheduled learning
      opportunities. A problem-based version of the guide introduced a clinical problem
      and encouraged the students to think of the learning outcome for the module as
      they related to the problem. Thirdly, an outcome-based version was structured
      round the 12 key areas of the learning outcomes. The timetable-based guide was
      preferred by the majority of students, although some preferred the problem-based
      guide and others the outcome-based guide. This may in part be due to students'
      lack of familiarity with a problem-based and outcome-based approach. It may also
      relate to what is seen as a key function of a study guide: to lead the student
      through the day-to-day learning experiences in a course and to introduce a
      student to a course or a topic and provide an overview of what is to be achieved
      in their studies of it.

PMID- 16807181
TI  - The OSCE: a new challenge to the evaluation system in Korea.
AB  - Introduced in Korea in 1994, the number of medical schools using Objective
      Structured Clinical Examination (OSCE) and standardized patients (SPs) has been
      steadily increasing. Although OSCE is accepted as an effective teaching and
      evaluation tool in Korea, many challenges in applying OSCE remain. These problems
      stem mainly from differences in the educational environment and infrastructure in
      medical schools between different countries. To reduce trial and error cost
      inefficiencies and to help accelerate the adaptation process, sharing experiences
      at all levels of applying OSCE to non-Western settings would be valuable. The
      authors describe how and to what extent the OSCE has been applied to the Korean
      medical education system. Additionally, the elements that should be in place for
      OSCE to successfully transform the national licensure examination into a high
      stakes examination are described.

PMID- 16807182
TI  - Hospital doctors' views of their CPD and its relationship to learning in the
      organization.
AB  - Continuing professional development (CPD) has traditionally been an autonomous,
      professional concern of doctors in the UK. In a changing educational and service
      climate, can individualized approaches to CPD be reconciled with adult learning
      principles and learning that is practice-based and multidisciplinary? A survey of
      the CPD of consultant and non-consultant career grade staff in Wales (UK) has
      provided some clues on how doctors perceive their learning needs in relation to
      those of Trust hospitals. It indicated that these doctors pursued traditional
      forms of continuing education (reading, lectures and meetings), gained clinical
      knowledge and changed their practice as a result. The majority saw themselves as
      accountable for CPD to their college and specialty. Trusts had yet to promote CPD
      as a clinical governance priority but respondents felt that appraisal helped to
      mediate individual and organizational perspectives of CPD. Most career-grade
      doctors believed their CPD activities met the needs of their employing
      organizations and felt satisfied with a 'traditional' approach to CPD. Doctors
      and service organizations may need to confront preconceptions regarding education
      and respective roles in the negotiation of CPD if team-based learning in practice
      is to become established.

PMID- 16807183
TI  - The use of personal digital assistants among medical residents.
AB  - The purpose of this study was to determine residents' perception of the utility
      of personal digital assistants (PDAs) and their influence on clinical practice at
      two teaching hospitals, one of which subsidized resident purchase of a PDA. A
      total of 21 residents in the unsubsidized group (32%) and 24 residents in the
      subsidized group (96%) owned a PDA. Medical residents who were provided with PDAs
      perceived them to be less useful than residents who were not provided with them.
      Palm owners in both groups responded that they used these devices to organize
      their record keeping and the most frequently used programs were pharmacopoeias,
      medical reference and clinical calculators. Residents quickly adapted PDA to
      clinical care and further research is needed to assess their impact on resident
      education and patient outcomes.

PMID- 16807184
TI  - Learning environments in medical education.

PMID- 16807185
TI  - Simulated patients and the development of procedural and operative skills.

PMID- 16807186
TI  - PBL patient scenarios were designed using five stages.

PMID- 16807187
TI  - The evaluation of dermatologic education in the postgraduate period.

PMID- 16807188
TI  - The influence of histology and embryology courses on student achievement in gross
      human anatomy courses.

PMID- 16807193
TI  - Cerebellar purkinje cell loss in heterozygous rora+/- mice: a longitudinal study.
AB  - The staggerer (sg) mutation is a spontaneous deletion in the Rora gene that
      prevents the translation of the ligand-binding domain (LBD), leading to the loss
      of RORalpha activity. The homozygous Rorasg/sg mutant mouse, whose most obvious
      phenotype is ataxia associated with cerebellar degeneration, also displays a
      variety of other phenotypes. The heterozygous Rora+/sg is able to develop a
      cerebellum that is qualitatively normal but which suffers a significant loss of
      cerebellar neuronal cells with advancing age. A truncated protein synthesized by
      the mutated allele may play a role both in Rorasg/sg and Rora+/sg. To determine
      the effects during life span of true haplo-insufficiency of the RORalpha protein,
      derived from the invalidation of the gene, we compared the evolution of Purkinje
      cell numbers in heterozygous Rora knock-out males (Rora+/-) and in their wild
      type counterparts from 1 to 24 months of age. We also compared the evolution of
      Purkinje cell (PC) numbers in Rora+/- and Rora+/sg males from 1 to 9 months. The
      main finding is that in Rora+/- mice, for which only one-half the normal amount
      of protein is produced, the deficit was established as early as 1 month and did
      not change during the animals' adult lifespans. Thus, the effects of aging on PC
      number were apparent much earlier in Rora+/- than in Rora+/sg, although at 24
      months of age the degrees of deficit were similar.

PMID- 16807194
TI  - The inheritance of cognitive skills: does genomic imprinting play a role?
AB  - Genomic imprinting refers to the differential expression of a gene based on
      parental origin. Animal and clinical studies have suggested that genomic
      imprinting is influential in brain development, with the maternal genome playing
      a disproportionate role in the development of the cortex. The present study
      investigated this phenomenon in a nonclinical human population, using
      intrafamilial correlations. Broadly consistent with predictions, it was found
      that abilities mediated by frontal, parietal, and temporal lobes, but not
      occipital lobes, were more closely correlated between children and mothers versus
      fathers. The implications of these findings for the prevailing theory of the
      evolution of genomic imprinting, and for the general study of genetics and
      behavior, are discussed.

PMID- 16807195
TI  - Behavioral genetics of caenorhabditis elegans unc-103-encoded erg-like K(+)
      channel.
AB  - The Caenorhabditis elegans unc-103 gene encodes a potassium channel whose
      sequence is most similar to the ether-a-go-go related gene (erg) type of K+
      channels. We find that the n 500 and e 1597 gain-of-function (gf) mutations in
      unc-103 cause reduced excitation in most muscles, while loss-of-function (lf)
      mutations cause mild muscle hyper-excitability. Both gf alleles change the same
      residue near the cytoplasmic end of S6, consistent with this region regulating
      channel activation. We also report additional dominant-negative and lf alleles of
      unc-103 that can antagonize or reduce the function of both gf and wild-type
      alleles. The unc-103 locus contains 6 promoter regions that express unc-103 in
      different combinations of body-wall and sex-specific muscles, motor-, inter- and
      sensory-neurons. Each promoter drives transcripts containing a unique first exon,
      conferring sequence variability to the N-terminus of the UNC-103 protein, while
      three splice variants introduce variability into the UNC-103 C-terminus. unc
      103(0) hermaphrodites prematurely lay embryos that would normally be retained in
      the uterus and lay eggs under conditions that inhibit egg-laying behavior. In the
      egg-laying circuit, unc-103 is expressed in vulval muscles and the HSN neurons
      from different promoters. Supplying the proper UNC-103 isoform to the vulval
      muscles is sufficient to restore regulation to egg-laying behavior.

PMID- 16807196
TI  - Age-related changes in event-cued visual and auditory prospective memory proper.
AB  - We rely upon prospective memory proper (ProMP) to bring back to awareness
      previously formed plans and intentions at the right place and time, and to enable
      us to act upon those plans and intentions. To examine age-related changes in
      ProMP, younger and older participants made decisions about simple stimuli
      (ongoing task) and at the same time were required to respond to a ProM cue,
      either a picture (visually cued ProM test) or a sound (auditorily cued ProM
      test), embedded in a simultaneously presented series of similar stimuli (either
      pictures or sounds). The cue display size or loudness increased across trials
      until a response was made. The cue size and cue loudness at the time of response
      indexed ProMP. The main results showed that both visual and auditory ProMP
      declined with age, and that such declines were mediated by age declines in
      sensory functions (visual acuity and hearing level), processing resources,
      working memory, intelligence, and ongoing task resource allocation.

PMID- 16807197
TI  - In-home cognitive training with older married couples: individual versus
      collaborative learning.
AB  - Research has demonstrated that older adults' cognitive performance can be
      enhanced via formal intervention, as well as more informal intervention including
      collaboration or working with a partner. The current study investigated the
      effects of an inductive reasoning training program adapted for in-home use among
      older adults assigned to individual training (n = 30), collaborative training (n
      = 34), or a no-treatment control group (n = 34). The training consisted of 10
      sessions, and all participants completed a pretest followed by a post-test 6
      weeks later. Findings suggest that older adults could effectively "train
      themselves" without the guidance of a formal instructor. The results, however,
      did not indicate immediate added benefit in reasoning performance for
      collaborative versus individual training using the current reasoning program.

PMID- 16807198
TI  - Flashbulb memories for September 11th can be preserved in older adults.
AB  - Flashbulb memories (FMs) are vivid, long-lasting memories for the source of
      surprising, arousing news. Laboratory studies have consistently found that older
      adults, especially those with below-average frontal lobe (FL) function, are
      impaired in source memory relative to young. We tested memory for the source of
      news concerning the September 11th terrorist attacks in older adults with high or
      low frontal lobe function and in young people. We found no age differences in
      source memory a year after the event and no differences related to FL function.
      Flashbulb memories may be different from usual cases of source memory because of
      their emotional content, personal importance, or social relevance.

PMID- 16807199
TI  - Competence in everyday activities as a predictor of cognitive risk and mortality.
AB  - This study examined the association of a performance-based measure of everyday
      functioning with clinically meaningful outcomes. Elderly participants in a
      prospective study of dementia were assessed at two occasions on the Everyday
      Problems Test for Cognitively Challenged Elderly (EPCCE), a performance-based
      measure of everyday functioning. Older adults who remained cognitively intact
      performed approximately 0.66 SD units higher on the EPCCE at both occasions than
      elders rated as impaired, when covarying on age, education, gender, and cognitive
      status. Relative to the nonimpaired participants, decline in EPCCE performance
      over a 2-year interval was significantly greater for impaired participants and
      those participants who transitioned from nonimpaired to impaired over the course
      of the study. Increased risk of mortality was associated with lower baseline
      scores and decline in EPCCE performance even after controlling for demographic
      variables and performance on the Mini-Mental State Examination. Given the
      clinical importance of identifying "at risk" elders for impairment, the findings
      from this study provide initial evidence for the predictive utility of
      performance-based measures of everyday functioning.

PMID- 16807200
TI  - Fluency, familiarity, aging, and the illusion of truth.
AB  - Research has shown that repeated statements are rated as more credible than new
      statements. However, little research has examined whether such "illusions of
      truth" can be produced by contextual (nonmnemonic) influences, or compared to the
      magnitude of these illusions in younger and older adults. In two experiments, we
      examined how manipulations of perceptual and conceptual fluency influenced truth
      and familiarity ratings made by young and older adults. Stimuli were claims about
      companies or products varying in normative familiarity. Results showed only small
      effects of perceptual fluency on rated truth or familiarity. In contrast,
      manipulating conceptual fluency via semantic/textual context had much larger
      effects on rated truth and familiarity, with the effects modulated by normative
      company familiarity such that fluency biases were larger for lesser-known
      companies. In both experiments, young and older adults were equally susceptible
      to fluency-based biases.

PMID- 16807201
TI  - Aging, task complexity, and efficiency modes: the influence of working memory
      involvement on age differences in response times for verbal and visuospatial
      tasks.
AB  - We examined the information-processing functions (response-time x load) of
      younger and older adults for two verbal and one visuo-spatial task; each task was
      implemented in a baseline and a high-complexity condition. Heightened complexity
      transformed the baseline functions in either an additive or a multiplicative
      fashion. The processing efficiency of older adults was defined as the old-young
      ratio of the slopes of the load functions. Three levels of efficiency could be
      distinguished. The first level, with an age-related slowing factor of about 1.2,
      consisted of low-complexity verbal processing and additive-complexity verbal
      processing. The second level, associated with a slowing factor of about 1.6,
      consisted of a mixture of verbal-high-multiplicative-complexity processing and
      visuo-spatial-low-complexity processing. The third level, with a slowing factor
      of about 4, consisted of visuo-spatial processing of high multiplicative
      complexity. The results go against any common factor theory of aging. Instead,
      they suggest that a shift from a higher to a lower mode of efficiency is
      triggered by a greater degree of working memory involvement.

PMID- 16807202
TI  - Dietary intake of organotin compounds in Finland: a market-basket study.
AB  - The objective of this study was to estimate the intake of organic tin compounds
      from foodstuffs in a Finnish market basket. The study was conducted by collecting
      13 market baskets from supermarkets and market places in the city of Kuopio,
      eastern Finland. Altogether 115 different food items were bought. In each basket,
      foodstuffs were mixed in proportion to their consumption and analysed by GC/MS
      for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and
      triphenyltin, and dioctyltin). Organotin compounds were detected in only four
      baskets, with the fish basket containing the largest number of different
      organotins. The European Food Safety Authority has established a tolerable daily
      intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin,
      triphenyltin and dioctyltin. According to this study, the daily intake of these
      compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish
      basket. This exposure is only 1% of the tolerable daily intake and poses
      negligible risk to the average consumer. However, for consumers eating large
      quantities of fish from contaminated areas, the intake may be much higher.

PMID- 16807203
TI  - Lead and cadmium in meat and meat products consumed by the population in Tenerife
      Island, Spain.
AB  - The aim of this study was to determine the levels of lead and cadmium in chicken,
      pork, beef, lamb and turkey samples (both meat and meat products), collected in
      the island of Tenerife (Spain). Lead and cadmium were measured by graphite
      furnace atomic absorption spectrometry (GFAAS). Mean concentrations of lead and
      cadmium were 6.94 and 1.68 microg kg(-1) in chicken meat, 5.00 and 5.49 microg
      kg(-1) in pork meat, 1.91 and 1.90 microg kg(-1) in beef meat and 1.35 and 1.22
      microg kg(-1) in lamb meat samples, respectively. Lead was below the detection
      limit in turkey samples and mean cadmium concentration was 5.49 microg kg(-1).
      Mean concentrations of lead and cadmium in chicken meat product samples were 3.16
      and 4.15 microg kg(-1), 4.89 and 6.50 microg kg(-1) in pork meat product, 6.72
      and 4.76 microg kg(-1) in beef meat product and 9.12 and 5.98 microg kg(-1) in
      turkey meat product samples, respectively. The percentage contribution of the two
      considered metals to provisional tolerable weekly intake (PTWI) was calculated
      for meat and meat products. Statistically significant differences were found for
      lead content in meats between the chicken and pork groups and the turkey and beef
      groups, whereas for cadmium concentrations in meats, significant differences were
      observed between the turkey and chicken, beef and lamb groups. In meat products,
      no clear differences were observed for lead and cadmium between the various
      groups.

PMID- 16807204
TI  - Relationship between physicochemical properties and maximum residue levels and
      tolerances of crop-protection products for crops set by the USA, European Union
      and Codex.
AB  - Residues on foodstuffs resulting from the use of crop-protection products are a
      function of many factors, e.g. environmental conditions, dissipation and
      application rate, some of which are linked to the physicochemical properties of
      the active ingredients. Residue limits (maximum residue levels (MRLs) and
      tolerances) of fungicides, herbicides and insecticides set by different
      regulatory authorities are compared, and the relationship between physicochemical
      properties of the active ingredients and residue limits are explored. This was
      carried out using simple summary statistics and artificial neural networks. US
      tolerances tended to be higher than European Union MRLs. Generally, fungicides
      had the highest residue limits followed by insecticides and herbicides.
      Physicochemical properties (e.g. aromatic proportion, non-carbon proportion and
      water solubility) and crop type explained up to 50% of the variation in residue
      limits. This suggests that physicochemical properties of the active ingredients
      may control important aspects of the processes leading to residues.

PMID- 16807205
TI  - Multi-residue method for the determination of 450 pesticide residues in honey,
      fruit juice and wine by double-cartridge solid-phase extraction/gas
      chromatography-mass spectrometry and liquid chromatography-tandem mass
      spectrometry.
AB  - A multi-residue method was developed for the determination of 450 pesticide
      residues in honey, fruit juice and wine using double-cartridge solid-phase
      extraction (SPE), gas chromatography-mass spectrometry (GC-MS) and liquid
      chromatography-tandem mass spectrometry (LC-MS-MS). The method development was
      based on an appraisal of the characteristics of GC-MS and LC-MS-MS for 654
      pesticides as well as the efficiency of extraction and purification from honey,
      fruit juice and wine. Samples were first diluted with water plus acetone, then
      extracted with portions of dichloromethane. The extracts were concentrated and
      cleaned up with graphitized carbon black and aminopropyl cartridges stacked in
      tandem. Pesticides were eluted with acetonitrile + toluene, and the eluates were
      concentrated. For 383 pesticides, the eluate was extracted with hexane twice and
      internal standard solution was added prior to GC-MS determination. For 67
      pesticides, extraction was with methanol prior to LC-MS-MS determination. The
      limit of detection for the method was between 1.0 and 300 ng g(-1) depending on
      each pesticide analyte. At the three fortification levels of 2.0-3000 ng g(-1),
      the average recovery rates were between 59 and 123%, among which 413 pesticides
      (92% of the 450) had recovery rates of 70-120% and 35 pesticides (8% of the 450)
      had recovery rates of 59-70%. There were 437 pesticides (97% of the 450) with a
      relative standard deviation below 25%; there were 13 varieties (3% of the 450)
      between 25.0 and 30.4%.

PMID- 16807206
TI  - Occurrence of aflatoxin M1 in retail milk samples from Bogota, Colombia.
AB  - A study was conducted to establish the occurrence and levels of contamination of
      aflatoxin M1 (AFM1) in retail milk from Bogota, Colombia. A total of 241 samples
      were analysed during 2004 and 2005. Samples were cleaned up by an immunoaffinity
      column and AFM1 was quantified by liquid chromatography with fluorescence
      detection. A total of 69.2 and 79.4% of the samples analysed during 2004 and
      2005, respectively, were found to contain levels of AFM1 above 10 ng l(-1).
      Levels of contamination ranged from 10.7 to 213.0 ng l(-1) in 2004, and from 10.6
      to 288.9 ng l(-1) in 2005. Despite the high incidence of AFM1 found in the milk
      samples analysed, all samples complied with current local regulations, which
      allow AFM1 content in milk up to 400 ng l(-1). However, due to the high incidence
      of AFM1 in milk found in the present study, it is recommended that a permanent
      surveillance programme be established for milk consumed in Bogota in order to
      prevent milk lots containing levels above the regulatory level entering the food
      chain.

PMID- 16807207
TI  - Production and characterization of a monoclonal antibody that cross-reacts with
      the mycotoxins nivalenol and 4-deoxynivalenol.
AB  - Nivalenol is a mycotoxin produced by certain fungi that are pathogenic to
      important cereal crops, in particular maize, wheat, and barley. This toxin,
      3alpha,4beta,7alpha,15-tetrahydroxy-12,13-epoxytrichothec-9-en-8-one, is found
      worldwide and is closely related to 4-deoxynivalenol (DON or vomitoxin), a
      mycotoxin associated with outbreaks of Fusarium head blight in North America. The
      literature on the toxicity of nivalenol suggests it is similar, if not more
      toxic, than DON. Despite the development of rapid immunologically based assays
      for detecting DON, such assays have not existed for detecting nivalenol without
      chemical modification of the analyte. This paper describes the development of a
      monoclonal antibody using a nivalenol-glycine protein conjugate. The monoclonal
      antibody was most specific for an acetylated form of DON (3-Ac-DON), but it
      exhibited sensitivity and cross-reactivity that were useful for detecting
      nivalenol and DON at relevant levels without the need to modify either toxin
      chemically. In an competitive indirect ELISA format, the concentrations of toxins
      able to inhibit colour development by 50% (IC50) were 1.7, 15.8, 27.5, 68.9, and
      1740 ng ml(-1) for the mycotoxins 3-Ac-DON, DON, nivalenol, 15-Ac-DON, and
      fusarenon-X, respectively. The antibody was also used to develop a competitive
      direct ELISA for DON and nivalenol, with IC50's of 16.5 ng ml(-1) (DON) and 33.4
      ng ml(-1) (nivalenol). These assays are capable of detecting both DON and
      nivalenol simultaneously, a property that may be useful in regions where these
      toxins co-occur or in formats, such as immunoaffinity columns, where co-isolation
      of both toxins is desirable.

PMID- 16807209
TI  - A simple steady-state model for carry-over of aflatoxins from feed to cow's milk.
AB  - A simple steady-state model is derived from two kinetic one-compartment models
      for the disposition of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the
      lactating cow. The model relates daily intake of AFB1 in feed of dairy cattle and
      the cow's lactation status to resulting concentrations of AFM1 in milk. Moreover,
      assuming a linear relationship between the cow's lactation status and feed
      intake, the model relates daily milk production and AFB1 concentration in total
      feed to AFM1 levels in milk. The model explains similar experimental outcomes
      from different investigations into carry-over of aflatoxins from feed to milk.
      Although it is difficult to set a permanent limit for AFB1 in feed, the European
      Union (EU) limit of 5 microg AFB1 kg(-1) concentrate has proved, thus far, to be
      an appropriate level in preventing the EU limit of 0.05 microg AFM1 kg(-1) milk
      being exceeded.

PMID- 16807208
TI  - International shipping of fumonisins from maize extracts on C18 sorbent.
AB  - Fumonisins are mycotoxins found in maize. In developing countries, the resources
      required for analysis are often lacking, and the shipping of maize between
      countries can be difficult since the importation of plant materials requires
      permits/inspection to prevent the entry of pests that frequently infest maize. A
      simple, safe and legal method for shipping maize extracts to the USA was needed
      to conduct a survey of fumonisins in Central America. The objective was to
      develop a method for isolating and shipping maize extracts for fumonisin analysis
      so as to facilitate a survey of fumonisin exposure. The results indicate that
      fumonisins in acetonitrile:water extracts of maize can be isolated on C18
      cartridges, held for at least 3 days at 22 degrees C and then an additional 4
      days at 4 degrees C before elution and analysis with no losses. This method
      allows the importation and analysis of maize samples from foreign locations
      without complications from international safety concerns.

PMID- 16807210
TI  - Analysis of vinylidene chloride and 1-chlorobutane in foods packaged with
      polyvinylidene chloride casing films by headspace gas chromatography/mass
      spectrometry (GC/MS).
AB  - A headspace gas chromatography/mass spectrometry method was developed for the
      simultaneous determination of vinylidene chloride and 1-chlorobutane in foods
      packaged with polyvinylidene chloride casing films. The solid foodstuff was
      homogenized with an equal mass of distilled water. The homogenate was incubated
      for 1 h at 90 degrees C in a sealed headspace vial, and the headspace gas was
      then analysed by gas chromatography/mass spectrometry in selected ion-monitoring
      mode using a bonded porous polymer-coated capillary column. The recovery rates of
      vinylidene chloride and 1-chlorobutane in foodstuffs were 94.5-103.9 and 85.8
      120.3%, respectively. Among 13 samples tested, vinylidene chloride was detected
      at 0.001-0.020 microg g(-1) in 11 foodstuffs, and 1-chlorobutane was detected at
      0.004-0.040 microg g(-1) in all 13 foodstuffs. Furthermore, vinylidene chloride
      was detected at 0.04 microg g(-1) in one casing film, and 1-chlorobutane was
      detected in all casing films. The results indicate that these compounds migrated
      from the casing films into the foodstuffs.

PMID- 16807211
TI  - Release of alpha-tocopherol from antioxidative low-density polyethylene film into
      fatty food simulant: influence of complexation in beta-cyclodextrin.
AB  - The release of alpha-tocopherol from two formulations (with and without
      complexation with beta-cyclodextrin) of low-density polyethylene (LDPE) film was
      examined. Specific migration studies were performed at 7.0 +/- 0.5 degrees C
      using plastic bags filled with 95% ethanol as a fatty food simulant. The amount
      of complexed and free (non-complexed) alpha-tocopherol migrating into the food
      simulant was followed by high-performance liquid chromatography (HPLC). It was
      concluded that complexation with beta-cyclodextrin had a significant effect on
      the release rate of the antioxidant. Using a mathematical model for the
      description of the migration, a decrease in diffusion coefficient (D) of one
      order of magnitude was calculated in the case of complexed alpha-tocopherol
      compared with the free form. Total migration of alpha-tocopherol from both films
      was observed, meaning that the partition coefficient of tocopherol was not
      influenced by incorporation with cyclodextrin. Thus, complexation might be the
      key to a long-lasting antioxidative effect of such kind of active packaging.

PMID- 16807212
TI  - Migration of dehydroabietic and abietic acids from paper and paperboard food
      packaging into food-simulating solvents and Tenax TA.
AB  - An investigation was undertaken to establish the concentration in paper products
      of dehydroabietic (DHA) and abietic (AA) resin acids, present in rosin, which are
      major toxicants of pulp- and paper-mill effluent. Their migration was studied
      from paper and paperboard products into various food-simulating solvents and the
      substitute fatty food simulant Tenax TA (modified polyphenylene oxide). DHA and
      AA were detected in five of 10 virgin paper products and in all 10 recycled
      paperboard products for food-contact use at concentrations of 14-500 and 110-1200
      microg/g, respectively. In virgin paper products, the highest migration was into
      95% ethanol or heptane, with negligible or no migration into other solvents. In
      recycled paperboard products, migration was highest into 95% ethanol, but was
      also observed into 20% ethanol, water and heptane. Migration to Tenax TA was also
      observed and the migration level increased with time. The maximum migration
      levels of DHA and AA into food simulants were 0.853 and 3.14 microg/g,
      respectively. The results suggest that, in the worst case, the daily intake of
      DHA and AA from paper and paperboard products was 50 times lower than the
      tolerable daily intake of rosin.

PMID- 16807213
TI  - The dangers and draw of online communication: pro-anorexia websites and their
      implications for users, practitioners, and researchers.
AB  - Recent advances in communication have enabled an underground interest group,
      unrestricted by geographic boarders, to evolve. The so-called pro-anorexia
      movement has a particular presence in the form of Internet discussion boards.
      This paper examines the potential impact of such online activity for those
      visiting these resources, for practitioners working with individuals who have
      anorexia, and for those conducting research into the condition. It contributes to
      the debate about this controversial development in the world of eating disorders.

PMID- 16807214
TI  - Eating disorder prevention research: a meta-analysis.
AB  - Eating disorder prevention programs have yielded mixed results and are somewhat
      controversial, primarily because of claims they may produce iatrogenic effects.
      We used meta-analysis to evaluate the effectiveness of eating disorder prevention
      programs and investigate moderators of intervention effects. Overall, prevention
      programs had large effects on improving knowledge and small net effects on
      reducing maladaptive eating attitudes and behaviors. Studies targeting
      participants at a relatively higher risk for developing an eating disorder
      produced greater benefits. Concerns about iatrogenic effects of including
      psychoeducational material on eating disorders were not supported by the data.
      These findings challenge conclusions drawn in previous review articles regarding
      the ineffectiveness of prevention programs and support the ability of eating
      disorder prevention programs to demonstrate behavioral improvements.

PMID- 16807215
TI  - Supporting friends and family members with eating disorders: discrepancies
      between intentions and reality.
AB  - This study examined how female undergraduate students anticipated they would
      approach a friend or family member with disordered eating and what kinds of
      support they believed to be helpful. The relationship between eating disorder
      symptomatology and anticipated approaches also was examined. Participants read
      vignettes depicting scenarios involving a friend or family member with disordered
      eating and described their anticipated approach. They also rated the helpfulness
      of various support attempts, and completed the EDI-2. Although collaborative
      approaches were rated more favorably than controlling approaches, 76% of
      responses generated by participants fell into the latter category. Reasons for
      the discrepancy between support attempts offered and those that are believed to
      be most helpful and the implications of these findings to the treatment and
      prevention of eating disorders are addressed.

PMID- 16807216
TI  - Daily spillover to and from binge eating in first-year university females.
AB  - Coping models of binge eating propose that stress and/or negative affect trigger
      binge eating, which serves to shift attention to the binge and its consequences.
      The current study tested these general assumptions using 14-day daily diary data
      collected from 66 first-year university females. Hierarchical Generalized Linear
      Modeling results showed that increased stress, negative affect, and weight
      concerns were associated with an increased likelihood of reporting symptoms of
      binge eating within days. Elevated weight concerns predicted next-day binge
      eating and binge eating predicted greater next-day negative affect. Discussion
      focuses on implications for coping models of binge eating.

PMID- 16807219
TI  - Stories I tell my patients: run by the numbers.

PMID- 16807220
TI  - The last word: stop the war on weight: obesity and eating disorder prevention
      working together toward health.

PMID- 16807221
TI  - Molecular Medicine and biomedical education: reshaping our mission.

PMID- 16807222
TI  - Molecular genetic aspects and pathophysiology of endocrine hypertension.

PMID- 16807223
TI  - Short stature and dysmorphology associated with defects in the SHOX gene.
AB  - Since its discovery in 1997, knowledge about the SHOX gene ( Short stature
      HOmeoboX-containing gene) has rapidly advanced. Although originally described as
      causing idiopathic short stature, SHOX mutations are also responsible for growth
      retardation in Leri-Weill dyschondrosteosis, Langer mesomelic dysplasia and
      Turner syndrome. Furthermore, SHOX has a broad functional scope and leads to a
      variety of different morphological-skeletal stigmata associated with these
      syndromes. This article reviews clinical and molecular data associated SHOX gene
      defects. Functional ongoing studies are expected to improve our understanding of
      the SHOX gene as comprising part of a genetic process responsible for normal
      growth and bone development.

PMID- 16807224
TI  - The problem of exogenous subclinical hyperthyroidism.
AB  - Over the past two decades a plethora of publications and clinical practice data
      have established that subclinical thyroid dysfunction is a common condition
      occurring much more frequently than the overt expression of thyroid disease.
      Subclinical hypothyroidism is considered to be the most common of these entities.
      However, far more common and relatively less studied is exogenous sublinical
      hyperthyroidism (SubHyper) caused by L-thyroxine (T4) administration to
      thyroidectomized or hypothyroid patients or patients with simple or nodular
      goiter. Despite iodination, simple goiter is still prevalent and single or
      multiple nodules are now detected by ultrasound screening in 25-30% of adults,
      who are accordingly frequently given long-term T4 treatment. Approximately half
      of European Endocrinologists administer T4 permanently to patients with the above
      entities with the aim of suppressing TSH levels. Furthermore, in the USA the
      Colorado Study demonstrated that 40% of patients receiving thyroid hormones had
      abnormal [corrected] TSH levels (i.e. lower than 0.3 or higher than 5.1 mU/L); of
      these, 0.9% had hyperthyroidism and 20.7% subclinical hyperthyroidism [corrected]
      These facts render exogenous SubHyper an everyday problem for the
      endocrinologist. Exogenous SubHyper differs in many aspects from endogenous, its
      principal difference being that it is an iatrogenic thyroid disorder induced by
      the endocrinologist. The management of exogenous SubHyper relies on appropriate
      adjustment of T4 dosage taking into consideration a) individual requirements in
      T4, sex, age and the presence of cardiovascular disease or other co-morbidity, b)
      the recognition that small changes in serum FT4 have a logarithmic effect on TSH,
      c) the variability of FT4-TSH interactions between individuals, d) the
      instability of T4 preparations and its bioavailability, and e) the values of
      serum FT4 and FT3 that accompany a suppressed TSH. This last parameter is of
      importance since it is the free thyroid hormones values in the serum that
      generate and reflect the thyroid metabolic state of the organism rather than the
      degree of TSH suppression.

PMID- 16807225
TI  - Early microvascular and macrovascular dysfunction is not accompanied by
      structural arterial injury in polycystic ovary syndrome.
AB  - OBJECTIVE: During the last decade cardiovascular risk factors and endothelial
      dysfunction have been shown to be present early in life in women with Polycystic
      Ovary Syndrome (PCOS). The aim of the present study was a global assessment of
      abnormalities in the arterial bed of young women with PCOS by non-invasive,
      reproducible methods. DESIGN: 27 women with PCOS and 27 control women of
      comparable age, body mass index and waist-to-hip ratio were studied.
      Macrovascular function was assessed by flow-mediated dilatation (FMD) on the
      brachial artery. Nitrate-induced dilatation (NID) was performed to exclude a
      vascular smooth muscle cells injury. Microvascular function was assessed by
      venous occlusion plethysmography studying forearm blood flow. Arterial structure
      was evaluated by ultrasonographic assessment of intima-media thickness (IMT) of
      the carotid artery. RESULTS: FMD values were lower in women with PCOS compared to
      controls (PCOS: 3.84+/-0.74% vs. controls: 9.83+/-0.97%, P<0.001), but no
      difference was observed in NID (PCOS: 16.59+/-1.84% vs. controls: 16.64+/-2.05%,
      P=0.98) values. The time required for reactive hyperemia to reach peak value, a
      plethysmography parameter, was longer in PCOS women (PCOS: 20.63+/-4.67 sec vs.
      controls: 10.38+/-5.11 sec, P=0.02). No difference was observed in the combined
      IMT among the studied groups (PCOS: 0.49+/-0.01 mm v.s. controls: 0.51+/-0.02 mm,
      P=0.19). CONCLUSIONS: Using non invasive methodologies endothelial dysfunction in
      the macrocirculation and early impairment in the microcirculation were
      demonstrated in young women with PCOS who had normal profile of glycemia,
      lipidemia and blood pressure, and no evidence of structural arterial impairment.

PMID- 16807226
TI  - Insulin resistance, growth factors and cytokine levels in overweight women with
      breast cancer before and after chemotherapy.
AB  - OBJECTIVE: To evaluate insulin values, insulin resistance, growth factors and
      cytokine levels in women suffering from breast cancer and the effect of
      chemotherapy on these parameters. DESIGN: In a prospective study, glucose and
      insulin values were determined in ten previously undiagnosed diabetic
      postmenopausal women with stage IV breast cancer (hepatic metastases excluded)
      during an oral glucose tolerance test (OGTT) carried out after a glucose load of
      75 g. At baseline, leptin, Interleukin-1 (IL-1), Interleukin-6 (IL-6),
      Interleukin-8 (IL-8), Insulin-Growth Factor-1 (IGF-1), Tumor-Necrosis-Factor
      alpha (TNF-alpha), Vascular Endothelial Growth Factor (VEGF) and Platelet Derived
      Growth Factor (PDGF) levels were also determined using appropriate methodolody.
      Insulin resistance and beta-cell function were calculated (HOMA-model). All women
      were evaluated prior to and after chemotherapy applied for 6 months. RESULTS: 1)
      Insulin levels at 120 minutes of the OGTT were higher before compared to post
      chemotherapy (Mean+/-SD: 170.39+/-78.07 vs 111.75+/-76.19, p=0.037). 2) Body mass
      index (BMI) was an important predictor of post-glucose load insulin levels both
      before (coefficient=1.051, p=0.004) and after chemotherapy (coefficient=0.711,
      p=0.003). 3) Before chemotherapy BMI values were positively related to PDGF
      levels (rs=0.685, p=0.029), while after chemotherapy this relationship became non
      significant (rs=0.188, p=0.603). Before chemotherapy there was a negative
      relationship between VEGF and waist circumference (coefficient= -0.542, p=0.023).
      CONCLUSIONS: Post-glucose load insulin values significantly decrease after
      chemotherapy. There is a positive relationship between BMI and post-glucose load
      insulin before and after chemotherapy. The contribution of the reduction in
      insulin, a known growth factor, to the outcome of chemotherapy in these patients
      remains speculative at present.

PMID- 16807227
TI  - Estradiol and progesterone supplementation during luteal phase improved the
      receptivity of the endometrium in a patient with a history of diethylstilboestrol
      exposure in-utero.
AB  - BACKGROUND: Diethylstilboestrol (DES) exposure in-utero has been shown to have
      negative effects on pregnancy. DES-exposed women are at increased risk of early
      spontaneous pregnancy loss, ectopic gestation and infertility. DESIGN: A 34-year
      old woman with a 6-year history of primary infertility is presented. The patient
      underwent in vitro fertilization (IVF) treatment without success. To improve the
      quality of the endometrium following IVF treatment, E2 and progesterone
      supplementation was added to the usual therapeutic regimen. The pregnancy
      progressed uneventfully and a normal female was born. CONCLUSIONS: This case
      indicates that the administration of E2 and progesterone in DES-exposed women
      might improve endometrium receptivity and consequently pregnancy outcome.

PMID- 16807228
TI  - Nobel prize winner Christian de Duve. From insulin to lysosomes.

PMID- 16807229
TI  - Cooperative fluctuations point to the dimerization interface of p53 core domain.
AB  - Elastic network models are used for investigation of the p53 core domain
      functional dynamics. Global modes of motion indicate high positive correlations
      for residue fluctuations across the A-B interface, which are not observed at the
      B-C interface. Major hinge formation is observed at the A-B interface upon
      dimerization indicating stability of the A-B dimer. These findings imply A-B as
      the native dimerization interface, whereas B-C is the crystal interface. The A-B
      dimer exhibits an opening-closing motion about DNA, supporting the previously
      suggested clamp-like model of nonspecific DNA binding followed by diffusion.
      Monomer A has limited positive correlations with DNA, while monomer B exhibits
      high positive correlations with DNA in the functionally significant slow modes.
      Thus, monomer B might seem to maintain the stability of the dimer-DNA complex by
      forming the relatively fixed arm of the dimer clamp, whereas the other arm of the
      clamp, monomer A, might allow sliding via continuous association/dissociation
      mechanisms.

PMID- 16807230
TI  - Coupling between lipid shape and membrane curvature.
AB  - Using molecular dynamics simulations, we examine the behavior of lipids whose
      preferred curvature can be systematically varied. This curvature is imposed by
      controlling the headgroup size of a coarse-grained lipid model recently developed
      by us. To validate this approach, we examine self-assembly of each individual
      lipid type and observe the complete range of expected bilayer and micelle phases.
      We then examine binary systems consisting of lipids with positive and negative
      preferred curvature and find a definite sorting effect. Lipids with positive
      preferred curvature are found in greater proportions in outer monolayers with the
      opposite observed for lipids with negative preferred curvature. We also observe a
      similar, but slightly stronger effect for lipids in a developing spherical bud
      formed by adhesion to a colloid (e.g., a viral capsid). Importantly, the
      magnitude of this effect in both cases was large only for regions with strong
      mean curvature (radii of curvature <10 nm). Our results suggest that lipid shape
      must act in concert with other physico-chemical effects such as phase transitions
      or interactions with proteins to produce strong sorting in cellular pathways.

PMID- 16807231
TI  - The C-terminal residues of bacteriophage T7 gene 4 helicase-primase coordinate
      helicase and DNA polymerase activities.
AB  - The gene 4 protein of bacteriophage T7 plays a central role in DNA replication by
      providing both helicase and primase activities. The C-terminal helicase domain is
      not only responsible for DNA-dependent dTTP hydrolysis, translocation, and DNA
      unwinding, but it also interacts with T7 DNA polymerase to coordinate helicase
      and polymerase activities. The C-terminal 17 residues of gene 4 protein are
      critical for its interaction with the T7 DNA polymerase/thioredoxin complex. This
      C terminus is highly acidic; replacement of these residues with uncharged
      residues leads to a loss of interaction with T7 DNA polymerase/thioredoxin and an
      increase in oligomerization of the gene 4 protein. Such an alteration on the C
      terminus results in a reduced efficiency in strand displacement DNA synthesis
      catalyzed by gene 4 protein and T7 DNA polymerase/thioredoxin. Replacement of the
      C-terminal amino acid, phenylalanine, with non-aromatic residues also leads to a
      loss of interaction of gene 4 protein with T7 DNA polymerase/thioredoxin.
      However, neither of these modifications of the C terminus affects helicase and
      primase activities. A chimeric gene 4 protein containing the acidic C terminus of
      the T7 gene 2.5 single-stranded DNA-binding protein is more active in strand
      displacement synthesis. Gene 4 hexamers containing even one subunit of a
      defective C terminus are defective in their interaction with T7 DNA polymerase.

PMID- 16807232
TI  - Essential residues in the C terminus of the bacteriophage T7 gene 2.5 single
      stranded DNA-binding protein.
AB  - Gene 2.5 of bacteriophage T7 encodes a single-stranded DNA (ssDNA)-binding
      protein (gp2.5) that is an essential component of the phage replisome. Similar to
      other prokaryotic ssDNA-binding proteins, gp2.5 has an acidic C terminus that is
      involved in protein-protein interactions at the replication fork and in
      modulation of the ssDNA binding properties of the molecule. We have used genetic
      and biochemical approaches to identify residues critical for the function of the
      C terminus of gp2.5. The presence of an aromatic residue in the C-terminal
      position is essential for gp2.5 function. Deletion of the C-terminal residue,
      phenylalanine, is detrimental to its function, as is the substitution of this
      residue with non-aromatic amino acids. Placing the C-terminal phenylalanine in
      the penultimate position also results in loss of function. Moderate shortening of
      the length of the acidic portion of the C terminus is tolerated when the aromatic
      nature of the C-terminal residue is preserved. Gradual removal of the acidic C
      terminus of gp2.5 results in a higher affinity for ssDNA and a decreased ability
      to interact with T7 DNA polymerase/thioredoxin. The replacement of the charged
      residues in the C terminus with neutral amino acids abolishes gp2.5 function. Our
      data show that both the C-terminal aromatic residue and the overall acidic charge
      of the C terminus of gp2.5 are critical for its function.

PMID- 16807234
TI  - BRCA1 suppresses osteopontin-mediated breast cancer.
AB  - BRCA1 is a well described breast cancer susceptibility gene thought to be
      involved primarily in DNA repair. However, mutation within the BRCA1
      transcriptional domain is also implicated in neoplastic transformation of mammary
      epithelium, but responsible mechanisms are unclear. Here we show in a rat mammary
      model system that wild type (WT) BRCA1 specifically represses the expression of
      osteopontin (OPN), a multifunctional estrogen-responsive gene implicated in
      oncogenic transformation, particularly that of the breast. WT.BRCA1 selectively
      binds OPN-activating transcription factors estrogen receptor alpha, AP-1, and
      PEA3, inhibits OPN promoter transactivation, and suppresses OPN mRNA and protein
      both from an endogenous gene and a relevant model inducible gene. WT.BRCA1 also
      inhibits OPN-mediated neoplastic transformation characterized by morphology
      change, anchorage-independent growth, adhesion to fibronectin, and invasion
      through Matrigel. A mutant BRCA1 allele (Mut.BRCA1) associated with familial
      breast cancer lacks OPN suppressor effects, binds to WT.BRCA1, and impedes
      WT.BRCA1 suppression of OPN. Stable transfection of rat breast tumor cell lines
      with Mut.BRCA1 dramatically up-regulates OPN protein and induces anchorage
      independent growth. In human primary breast cancer, BRCA1 mutation is
      significantly associated with OPN overexpression. Taken together, these data
      suggest that BRCA1 mutation may confer increased tissue-specific cancer risk, in
      part by disruption of BRCA1 suppression of OPN gene transcription.

PMID- 16807233
TI  - Large store-operated calcium selective currents due to co-expression of Orai1 or
      Orai2 with the intracellular calcium sensor, Stim1.
AB  - The molecular nature of store-operated Ca(2+)-selective channels has remained an
      enigma, due largely to the continued inability to convincingly demonstrate Ca(2+)
      selective store-operated currents resulting from exogenous expression of known
      genes. Recent findings have implicated two proteins, Stim1 and Orai1, as having
      essential roles in store-operated Ca(2+) entry across the plasma membrane.
      However, transient overexpression of these proteins on their own results in
      little or no increase in store-operated entry. Here we demonstrate dramatic
      synergism between these two mediators; co-transfection of HEK293 cells with Stim1
      and Orai1 results in an approximate 20-fold increase in store-operated Ca(2+)
      entry and Ca(2+)-selective current. This demonstrates that these two proteins are
      limiting for both the signaling and permeation mechanisms for Ca(2+)-selective
      store-operated Ca(2+) entry. There are three mammalian homologs of Orai1, and in
      expression experiments they all produced or augmented store-operated Ca(2+) entry
      with efficacies in the order Orai1 > Orai2 > Orai3. Stim1 apparently initiates
      the signaling process by acting as a Ca(2+) sensor in the endoplasmic reticulum.
      This results in rearrangement of Stim1 within the cell and migration toward the
      plasma membrane to regulate in some manner Orai1 located in the plasma membrane.
      However, we demonstrate that Stim1 does not incorporate in the surface membrane,
      and thus likely regulates or interacts with Orai1 at sites of close apposition
      between the plasma membrane and an intracellular Stim1-containing organelle.

PMID- 16807235
TI  - AI-1 influences the kinase activity but not the phosphatase activity of LuxN of
      Vibrio harveyi.
AB  - The Gram-negative bacterium Vibrio harveyi produces and responds to three
      autoinducers, AI-1, AI-2, and CAI-1 to regulate cell density dependent gene
      expression by a process referred to as quorum sensing. The concentration of the
      autoinducers is sensed by three cognate hybrid sensor kinases, and information is
      channeled via the HPt protein LuxU to the response regulator LuxO. Here, a
      detailed biochemical study on the enzymatic activities of the membrane-integrated
      hybrid sensor kinase LuxN, the sensor for N-(d-3-hydroxybutanoyl)homoserine
      lactone (AI-1), is provided. LuxN was heterologously overproduced as the full
      length protein in Escherichia coli. LuxN activities were characterized in vitro
      and are an autophosphorylation activity with an unusually high ATP turnover rate,
      stable LuxU phosphorylation, and a slow phosphatase activity with LuxU
      approximately P as substrate. The presence of AI-1 affected the kinase but not
      the phosphatase activity of LuxN. The influence of AI-1 on the LuxN--> LuxU
      signaling step was monitored, and in the presence of AI-1, the kinase activity of
      LuxN, and hence the amount of LuxU approximately P produced, were significantly
      reduced. Half-maximal inhibition of kinase activity by AI-1 occurred at 20 mum.
      Together, these results indicate that AI-1 directly interacts with LuxN to down
      regulate its autokinase activity and suggest that the key regulatory step of the
      AI-1 quorum sensing system of Vibrio harveyi is AI-1-mediated repression of the
      LuxN kinase activity.

PMID- 16807236
TI  - CCL5-CCR5-mediated apoptosis in T cells: Requirement for glycosaminoglycan
      binding and CCL5 aggregation.
AB  - CCL5 (RANTES (regulated on activation normal T cell expressed and secreted)) and
      its cognate receptor, CCR5, have been implicated in T cell activation. CCL5
      binding to glycosaminoglycans (GAGs) on the cell surface or in extracellular
      matrix sequesters CCL5, thereby immobilizing CCL5 to provide the directional
      signal. In two CCR5-expressing human T cell lines, PM1.CCR5 and MOLT4.CCR5, and
      in human peripheral blood-derived T cells, micromolar concentrations of CCL5
      induce apoptosis. CCL5-induced cell death involves the cytosolic release of
      cytochrome c, the activation of caspase-9 and caspase-3, and poly(ADP-ribose)
      polymerase cleavage. CCL5-induced apoptosis is CCR5-dependent, since native PM1
      and MOLT4 cells lacking CCR5 expression are resistant to CCL5-induced cell death.
      Furthermore, we implicate tyrosine 339 as a critical residue involved in CCL5
      induced apoptosis, since PM1 cells expressing a tyrosine mutant receptor,
      CCR5Y339F, do not undergo apoptosis. We show that CCL5-CCR5-mediated apoptosis is
      dependent on cell surface GAG binding. The addition of exogenous heparin and
      chondroitin sulfate and GAG digestion from the cell surface protect cells from
      apoptosis. Moreover, the non-GAG binding variant, (44AANA47)-CCL5, fails to
      induce apoptosis. To address the role of aggregation in CCL5-mediated apoptosis,
      nonaggregating CCL5 mutant E66S, which forms dimers, and E26A, which form
      tetramers at micromolar concentrations, were utilized. Unlike native CCL5, the
      E66S mutant fails to induce apoptosis, suggesting that tetramers are the minimal
      higher ordered CCL5 aggregates required for CCL5-induced apoptosis. Viewed
      altogether, these data suggest that CCL5-GAG binding and CCL5 aggregation are
      important for CCL5 activity in T cells, specifically in the context of CCR5
      mediated apoptosis.

PMID- 16807237
TI  - DNA damage-induced down-regulation of human Cdc25C and Cdc2 is mediated by
      cooperation between p53 and maintenance DNA (cytosine-5) methyltransferase 1.
AB  - The Cdc25C phosphatase mediates cellular entry into mitosis in mammalian cells.
      Cdc25C activates Cdc2 for entry into mitosis by dephosphorylating Thr and Tyr at
      the site of inhibitory phosphorylation. The Cdc25C gene contains tumor suppressor
      p53 binding sites and is demonstrated to contribute to the p53-dependent cell
      cycle arrest upon DNA damage. Here we show that both Cdc25C and Cdc2 were down
      regulated in wild-type HCT116 cells but not in p53-null, DNMT1-null or DNMT1and
      DNMT3b-null cells, upon p53 stabilization following doxorubicin-mediated DNA
      damage. Furthermore, zebularine, a drug that selectively traps and depletes
      nuclear DNMT1 and DNMT3b, relieved p53-mediated repression of endogenous Cdc25C
      and Cdc2. Methylation analysis of the Cdc25C and Cdc2 promoter displayed internal
      CG methylation proximal to the p53 binding site upon DNA damage in a p53
      dependent manner. Chromatin immunoprecipitation of doxorubicin treated wild-type
      HCT116 cells showed the presence of DNMT1, p53, H3K9me2, and the transcriptional
      repressor HDAC1 on the Cdc25C and Cdc2 promoters, suggesting their involvement as
      repressive complexes in Cdc25C and Cdc2 gene silencing. Thus, the general
      mechanism of p53-mediated gene repression may involve recruitment of other
      repressive factors.

PMID- 16807238
TI  - Osteopontin induction of hyaluronan synthase 2 expression promotes breast cancer
      malignancy.
AB  - Osteopontin (OPN) is a tumor-associated, secreted phosphoprotein that has been
      implicated in breast cancer progression and metastasis. Research concerning how
      OPN functions in tumor progression has led to the identification of a limited
      number of genes that contribute functionally to OPN-induced cellular behaviors.
      Recent microarray analysis, comparing 21NT breast cancer cells transfected to
      constitutively overexpress OPN with control cells, revealed hyaluronan synthase 2
      (HAS2) to be a gene highly up-regulated in OPN-overexpressing cells. In this
      study, we further examined the relationship between OPN and HAS2. We show that
      21NT OPN-transfected cells express high levels of HAS2, which is associated with
      increased HA production and matrix retention and is necessary for tumor cell
      adhesion to bone marrow endothelial cells and anchorage-independent growth.
      Finally, stable transfection of antisense HAS2 into 21NT cells overexpressing OPN
      resulted in a reduction in HAS2 expression, HA production, and pericellular
      retention. Antisense-mediated down-regulation of HAS2 also resulted in a
      significant decrease in cellular proliferation and colony growth in soft agar. To
      our knowledge, this is the first report of the ability of OPN to regulate HAS2
      expression and HA production in breast cancer cells and further illustrates a
      unique functional relationship by which enhanced HA production facilitates OPN
      mediated cell behaviors.

PMID- 16807239
TI  - Catalytic importance of acidic amino acids on subunit NuoB of the Escherichia
      coli NADH:ubiquinone oxidoreductase (complex I).
AB  - The NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli is composed
      of 13 subunits called NuoA through NuoN and contains one FMN and 9 iron-sulfur
      clusters as redox groups. Electron transfer from NADH to ubiquinone is coupled
      with the translocation of protons across the membrane by a yet unknown mechanism.
      Redox-induced Fourier transform infrared difference spectroscopy showed that the
      oxidation of iron-sulfur cluster N2 located on NuoB is accompanied by the
      protonation of acidic amino acid(s). Here, we describe the effect of mutating the
      conserved acidic amino acids on NuoB. The complex was assembled in all mutants
      but the electron transfer activity was completely abolished in the mutants E67Q,
      D77N, and D94N. The complex isolated from these mutants contained N2 although in
      diminished amounts. The protonation of acidic amino acid(s) coupled with the
      oxidation of N2 was not detectable in the complex from the mutant E67Q. However,
      the conservative mutations E67D and D77E did not disturb the enzymatic activity,
      and the signals because of the protonation of acidic amino acid(s) were
      detectable in the E67D mutant. We discuss the possible participation of Glu(67)
      in a proton pathway coupled with the redox reaction of N2.

PMID- 16807240
TI  - Mechanistic coupling of bacteriophage T4 DNA packaging to components of the
      replication-dependent late transcription machinery.
AB  - Regulation of the terminal stage of viral DNA development, DNA packaging, is
      poorly understood. A new phage T4 in vitro DNA packaging assay employed purified
      proheads, terminase (gp17 + gp16), and ATP to encapsidate DNA resistant to
      nuclease. Mature phage T4 DNA and linearized plasmid DNAs containing or lacking a
      cloned T4 gene were packaged with high (approximately 10%) efficiency.
      Supercoiled, relaxed covalently closed, and nicked circular plasmid DNAs were
      packaged inefficiently, if at all, by these components. However, efficient
      packaging is achieved for nicked circular plasmid DNA, but not covalently closed
      plasmid DNA, upon addition to packaging mixtures of the purified T4 late
      transcription-replication machinery proteins: gp45 (sliding clamp), gp44/gp62
      (clamp loader complex), gp55 (late sigma-factor), and gp33 (transcriptional co
      activator). The small terminase subunit (gp16) is inhibitory for packaging linear
      DNAs, but enhances the transcription-replication protein packaging of nicked
      plasmid DNA. Taken together with genetic and biochemical evidence of a
      requirement for gp55 for concatemer packaging to assemble active wild-type phage
      particles (1), the plasmid packaging results show that initiation of phage T4
      packaging on "endless" concatemeric DNA in vivo by terminase depends upon
      interaction with the DNA loaded gp45 coupled late transcription-replication
      machinery. The results suggest a close mechanistic connection in vivo between DNA
      packaging and developmentally concurrent replication-dependent late
      transcription.

PMID- 16807241
TI  - Hierarchic finite level energy landscape model: to describe the refolding
      kinetics of phosphoglycerate kinase.
AB  - One of the most intriguing predictions of energy landscape models is the
      existence of non-exponential protein folding kinetics caused by hierarchical
      structures in the landscapes. Here we provide the strongest evidence so far of
      such hierarchy and determine the time constants and weights of the kinetic
      components of the suggested hierarchic energy landscape. To our knowledge, the
      idea of hierarchical folding energy barriers has never been tested over such a
      broad timescale. Refolding of yeast phosphoglycerate kinase was initiated from
      the guanidine-unfolded state by stopped-flow or manual mixing and monitored by
      tryptophan fluorescence from 1 ms to 15 min. The strategy to build a model that
      describes folding of yeast phosphoglycerate kinase was to start from the simplest
      paradigm and modify it stepwise to the necessary minimal extent after repeated
      comparisons with the experiments. We made no a priori assumptions about the
      folding landscape. The result was a hierarchic finite level landscape model that
      quantitatively describes the refolding of yeast phosphoglycerate kinase from 1 ms
      to 15 min. The early steps of the folding process happen in the upper region of
      the landscape, where the surface has a hierarchic structure. This leads to
      stretched kinetics in the early phase of the folding. The lower region of the
      energy landscape is dominated by a trap that reflects the accumulation of molten
      globule intermediate state. From this intermediate, the protein can reach the
      global energy minimum corresponding to the native state through a cross-barrier
      folding step.

PMID- 16807242
TI  - The PUB domain functions as a p97 binding module in human peptide N-glycanase.
AB  - The AAA ATPase p97 is a ubiquitin-selective molecular machine involved in
      multiple cellular processes, including protein degradation through the ubiquitin
      proteasome system and homotypic membrane fusion. Specific p97 functions are
      mediated by a variety of cofactors, among them peptide N-glycanase, an enzyme
      that removes glycans from misfolded glycoproteins. Here we report the three
      dimensional structure of the aminoterminal PUB domain of human peptide N
      glycanase. We demonstrate that the PUB domain is a novel p97 binding module
      interacting with the D1 and/or D2 ATPase domains of p97 and identify an
      evolutionary conserved surface patch required for p97 binding. Furthermore, we
      show that the PUB and UBX domains do not bind to p97 in a mutually exclusive
      manner. Our results suggest that PUB domain-containing proteins constitute a
      widespread family of diverse p97 cofactors.

PMID- 16807243
TI  - Structural insights into HypB, a GTP-binding protein that regulates metal
      binding.
AB  - HypB is a prokaryotic metal-binding guanine nucleotide-binding protein that is
      essential for nickel incorporation into hydrogenases. Here we solved the x-ray
      structure of HypB from Methanocaldococcus jannaschii. It shows that the G-domain
      has a different topology than the Ras-like proteins and belongs to the SIMIBI
      (after Signal Recognition Particle, MinD and BioD) class of NTP-binding proteins.
      We show that HypB undergoes nucleotide-dependent dimerization, which is
      apparently a common feature of SIMIBI class G-proteins. The nucleotides are
      located in the dimer interface and are contacted by both subunits. The active
      site features residues from both subunits arguing that hydrolysis also requires
      dimerization. Two metal-binding sites are found, one of which is dependent on the
      state of bound nucleotide. A totally conserved ENV/IGNLV/ICP motif in switch II
      relays the nucleotide binding with the metal ionbinding site. The homology with
      NifH, the Fe protein subunit of nitrogenase, suggests a mechanistic model for the
      switch-dependent incorporation of a metal ion into hydrogenases.

PMID- 16807244
TI  - Heparan sulfate-related oligosaccharides in ternary complex formation with
      fibroblast growth factors 1 and 2 and their receptors.
AB  - Biosynthesis of heparan sulfate (HS) is strictly regulated to yield products with
      cell/tissue-specific composition. Interactions between HS and a variety of
      proteins, including growth factors and morphogens, are essential for embryonic
      development and for homeostasis in the adult. Fibroblast growth factors (FGFs)
      and their various receptors (FRs) form ternary complexes with HS, as required for
      receptor signaling. Libraries of HS-related, radiolabeled oligosaccharides were
      generated by chemo-enzymatic modification of heparin and tested for affinity to
      immobilized FR ectodomains in the presence of FGF1 or FGF2. Experiments were
      designed to enable assessment of N-sulfated 8- and 10-mers with defined numbers
      of iduronic acid 2-O-sulfate and glucosamine 6-O-sulfate groups. FGF1 and FGF2
      were found to require similar oligosaccharides in complex formation with FR1c-3c,
      FGF2 affording somewhat more efficient oligosaccharide recruitment than FGF1.
      FR4, contrary to FR1c-3c, bound oligosaccharides at physiological ionic
      conditions even in the absence of FGFs, and this interaction was further promoted
      by FGF1 but not by FGF2. In all systems studied, the stability of FGF
      oligosaccharide-FR complexes correlated with the overall level of saccharide O
      sulfation rather than on the precise distribution of sulfate groups.

PMID- 16807245
TI  - Serglycin is the major secreted proteoglycan in macrophages and has a role in the
      regulation of macrophage tumor necrosis factor-alpha secretion in response to
      lipopolysaccharide.
AB  - It has recently been shown that serglycin is essential for maturation of mast
      cell secretory granules. However, serglycin is expressed also by other cell
      types, and in this study we addressed the role of serglycin in macrophages.
      Adherent cells were prepared from murine peritoneal cell populations and from
      spleens, and analyzed for proteoglycan synthesis by biosynthetic labeling with
      [35S]sulfate. Conditioned media from serglycin-/- peritoneal macrophages and
      adherent spleen cells displayed a 65-80% reduction of 35S-labeled proteoglycans,
      compared with corresponding material from serglycin+/+ cells, indicating that
      serglycin is the dominant secretory proteoglycan in macrophages of these origins.
      In contrast, the levels of intracellular proteoglycans were similar in
      serglycin+/+ and serglycin-/- cells, suggesting that serglycin is not stored
      intracellularly to a major extent in macrophages. This is in contrast to mast
      cells, in which serglycin is predominantly stored intracellularly. Transmission
      electron microscopy revealed that the absence of serglycin did not cause any
      major morphological effects on peritoneal macrophages, in contrast to dramatic
      defects in intracellular storage vesicles in peritoneal mast cells. Several
      secretory products were not found to be affected by the lack of serglycin.
      However, the secretion of tumor necrosis factor-alpha in response to
      lipopolysaccharide stimulation was markedly higher in serglycin-/- cultures than
      in those of serglycin+/+. The present report thus demonstrates that serglycin is
      the major proteoglycan secreted by peritoneal macrophages and suggests that the
      macrophage serglycin may have a role in regulating secretion of tumor necrosis
      factor-alpha.

PMID- 16807246
TI  - Syndecan-1 expression in epithelial cells is induced by transforming growth
      factor beta through a PKA-dependent pathway.
AB  - Syndecans comprise a major family of cell surface heparan sulfate proteoglycans
      (HSPGs). Syndecans bind and modulate a wide variety of biological molecules
      through their heparan sulfate (HS) moiety. Although all syndecans contain the
      ligand binding HS chains, they likely perform specific functions in vivo because
      their temporal and spatial expression patterns are different. However, how
      syndecan expression is regulated has yet to be clearly defined. In this study, we
      examined how syndecan-1 expression is regulated in epithelial cells. Our results
      showed that among several bioactive agents tested, only forskolin and three
      isoforms of TGFbeta (TGFbeta1-TGFbeta3) significantly induced syndecan-1, but not
      syndecan-4, expression on various epithelial cells. Steady-state syndecan-1 mRNA
      was not increased by TGFbeta treatment and cycloheximide did not inhibit syndecan
      1 induction by TGFbeta, indicating that TGFbeta induces syndecan-1 in a post
      translational manner. However, TGFbeta induction of syndecan-1 was inhibited by
      transient expression of a dominant-negative construct of protein kinase A (PKA)
      and by specific inhibitors of PKA. Further (i) syndecan-1 cytoplasmic domains
      were Ser-phosphorylated when cells were treated with TGFbeta and this was
      inhibited by a PKA inhibitor, (ii) PKA was co-immunoprecipitated from cell
      lysates by anti-syndecan-1 antibodies, (iii) PKA phosphorylated recombinant
      syndecan-1 cytoplasmic domains in vitro, and (iv) expression of a syndecan-1
      construct with its invariant Ser(286) replaced with a Gly was not induced by
      TGFbeta. Together, these findings define a regulatory mechanism where TGFbeta
      signals through PKA to phosphorylate the syndecan-1 cytoplasmic domain and
      increases syndecan-1 expression on epithelial cells.

PMID- 16807247
TI  - Solution structure and antiestrogenic activity of the unique C-terminal, NR-box
      motif-containing region of MTA1s.
AB  - Metastasis tumor-associated 1 short form (MTA1s) is a naturally occurring,
      alternatively spliced variant of MTA1 that functions as a repressor of estrogen
      receptor (ER) alpha transcriptional functions, at least in part by binding and
      sequestering ERalpha in the cytoplasm. A unique C-terminal 33-amino acid region
      containing a nuclear receptor (NR)-box motif (-LRILL-) mediates binding of MTA1s
      with ERalpha and is indispensable in this interaction. Here, we elucidated the
      solution structure of this 33-amino acid region by NMR spectroscopy. We found a
      predominance of the alpha-helical region toward the N-terminal region, which
      includes the NR-box motif. In silico docking and comparison studies showed
      similarities between the NR-box motif of MTA1s and a similar motif of
      coregulators, both in structure and mode of ERalpha binding. In MCF-7 breast
      cancer cells, the MTA1s peptide effectively repressed ERalpha transactivation
      function, as evidenced by the estrogen response element-luc assay and down
      regulation of estrogen-induced genes. In mechanistic studies, we found that the
      antiestrogenic effects of the MTA1s peptide were due to its ability to compete
      with the coactivator recruitment to ERalpha. Furthermore, the peptide efficiently
      repressed estrogen-induced proliferation and anchorage-independent growth of MCF
      7 cells. In addition, the MTA1s peptide blocked the progression of tumors formed
      by MCF-7 cells overexpressing an ERalpha coactivator in a xenograft-based assay.
      In brief, the characterization of structure and antiestrogenic activity of MTA1s
      peptide highlight its therapeutic potential.

PMID- 16807248
TI  - Regulation of survivin stability by the aryl hydrocarbon receptor-interacting
      protein.
AB  - Survivin is a multifunctional member of the IAP (inhibitor of apoptosis) family,
      but its molecular interactions in protection from cell death and regulation of
      cell division have not been completely elucidated. In a proteomics screening to
      identify novel survivin-binding partners, we found that the aryl hydrocarbon
      receptor-interacting protein (AIP) directly associates with survivin in vitro and
      in co-immunoprecipitation experiments in vivo. This interaction is mediated by
      the carboxyl-terminal end of AIP, which contains three tetratricopeptide motifs,
      and involves the carboxyl terminus coiled coil in survivin with critical roles of
      Asp(142) in AIP recognition. A survivin mutant lacking only Asp(142) fails to
      bind AIP and exhibits accelerated degradation in vivo in a reaction reversed by a
      proteasome inhibitor. Acute knock-down of AIP by short interference RNA or
      competition of the survivin-AIP complex by peptidyl mimicry destabilizes survivin
      levels in cells, with enhanced apoptosis but no changes in cell cycle
      progression. Therefore, AIP regulates survivin stability, thus elevating a
      cellular anti-apoptotic threshold. The survivin-AIP complex may influence the
      cellular xenobiotic response to environmental toxin(s) and contribute to
      subcellular chaperone trafficking during cell death regulation.

PMID- 16807249
TI  - CCAAT/enhancer-binding protein alpha mediates induction of hepatic
      phosphoenolpyruvate carboxykinase by p38 mitogen-activated protein kinase.
AB  - Excessive hepatic gluconeogenesis and glucose production are important
      contributors to hyperglycemia in both type 1 and type 2 diabetes. In diabetic
      humans and animal models, elevated levels of p38 mitogen-activated protein kinase
      (p38) are observed in several tissues. Our study shows that activity of p38 is
      significantly elevated in livers of db/db or streptozocin-induced type 1 diabetic
      mice. Using cultured hepatoma cells, we find that activation of p38 enhances
      expression of hepatic gluconeogenic gene phosphoenolpyruvate carboxykinase
      (PEPCK). Furthermore, our studies demonstrate that activation of p38 stimulates
      phosphorylation of CCAAT/enhancer-binding protein alpha (C/EBPalpha) at serine 21
      and increases its transactivation activity in the context of PEPCK gene
      transcription. Our results indicate that C/EBPalpha mediates p38-stimulated PEPCK
      transcription in liver cells.

PMID- 16807250
TI  - Benefits and concerns of simplification strategies in HIV-infected patients.
AB  - Highly active antiretroviral therapies (HAART) provide sustained viral control in
      most patients, but many of these regimens are restricted by complex dosing, drug
      drug interactions and toxicities. Numerous strategies of simplified treatment
      have been explored in order to improve patient quality of life and adherence to
      treatment, as well as to manage drug-related toxicities while maintaining viral
      suppression. The first simplification strategy involved switching from protease
      inhibitors (PIs) to non-nucleoside reverse transcriptase inhibitors (NNRTIs),
      with an additional benefit on lipid metabolism. The development of once-daily
      drugs or co-formulated combinations has successfully been used to further
      simplify treatment. However, studies assessing triple nucleoside regimens have
      shown a higher frequency of viral failure in comparison with standard HAART,
      mainly in patients with previous sequential suboptimal treatments. Finally, NRTI
      sparing approaches, consisting of NNRTI+PI combinations or monotherapies with
      boosted PIs, are alternatives to avoid NRTI-related mitochondrial toxicities. An
      accurate analysis of each patient's history will be necessary in each case to
      determine whether a simplification strategy is appropriate.

PMID- 16807251
TI  - Antibacterial activity of YC-20, a new oxazolidinone.
AB  - OBJECTIVES AND METHODS: YC-20 is a novel oxazolidinone that has targeted activity
      against Gram-positive bacteria. The in vitro activity of YC-20 and 6 comparators
      against 522 clinical isolates of Gram-positive species was determined. RESULTS:
      YC-20 is a potent oxazolidinone with all isolates tested displaying MIC50 and
      MIC90 values of <0.5 and 2 mg/L, respectively. MICs of YC-20 for all isolates
      tested, with the exception of methicillin-susceptible Staphylococcus epidermidis,
      were similar or lower than those of linezolid. CONCLUSIONS: This study suggests a
      potential new antibiotic for the treatment of infections with Gram-positive
      bacteria.

PMID- 16807252
TI  - Comparability of laboratory diagnosis and antimicrobial susceptibility testing of
      Neisseria gonorrhoeae from reference laboratories in Western Europe.
AB  - OBJECTIVES: The aim of this study was to obtain information on the comparability
      of methods for the laboratory diagnosis of bacterial sexually transmitted
      infections (STIs) that contribute to the surveillance data in the European Union
      (EU) and Norway. Surveillance of bacterial STIs is important across Europe
      because of the movement of individuals between countries at a time when STI
      incidence appears to be increasing in many countries. METHODS: Cross-sectional
      survey using a questionnaire, to provide information on laboratory methods for
      the diagnosis of gonorrhoea, and a panel of strains of Neisseria gonorrhoeae, to
      compare susceptibility testing, was circulated to laboratories in the EU and
      Norway. RESULTS: The questionnaire revealed marked diversity in the methodologies
      used for the laboratory diagnosis of gonorrhoea across Europe. Fourteen
      laboratories participated in an exchange of gonococcal strains to assess the
      methodology in current use for susceptibility testing. The methods included disc
      diffusion and determination of the minimum inhibitory concentration (MIC) using
      agar dilution and/or Etest. There was no common method used, each centre varied
      from another by at least one procedure. Overall agreement using all methods was
      >70%, being highest for ceftriaxone and lowest for tetracycline. Disc diffusion
      gave the lowest agreement with the consensus compared with determination of MIC
      by either agar dilution or Etest. CONCLUSIONS: A variety of methods were used
      across the EU and Norway for the laboratory diagnosis and susceptibility testing
      and resulted in poor concordance between laboratories on the definition of
      resistant N. gonorrhoeae. This suggests that there is a need for greater
      standardization of methodology that provides surveillance data in the EU and
      Norway.

PMID- 16807253
TI  - Characterization of defective beta-lactamase genes in Yersinia enterocolitica.
AB  - OBJECTIVES: To study at the molecular level the heterogeneity of expression of
      the two chromosomal beta-lactamases, BlaA and BlaB, in Yersinia enterocolitica
      strains isolated from clinical samples. METHODS: MIC determination by the agar
      dilution method and beta-lactamase assays was performed to determine the
      resistance level conferred by these enzymes. DNA cloning, PCR and direct
      sequencing were used to detect the presence of mutations. RESULTS: The blaA
      allele from strain IP97 (blaA97) was found to carry a deletion of 51 bp which
      entirely abolished its beta-lactamase activity. Both the ampR gene and the
      promoter region of strain Y56 were shown to be functional by a gene swapping
      experiment. The blaB allele from strain Y56 was found to carry two point
      mutations, only one of them resulting in a change in the amino acid sequence of
      the protein. This single amino acid change created a practically inactive BlaB or
      AmpC cephalosporinase in Y. enterocolitica Y56. CONCLUSIONS: The lack of activity
      observed in the beta-lactamases of some Y. enterocolitica isolates was due to the
      presence of point mutations or small deletions in the corresponding genes.

PMID- 16807254
TI  - Timing of vancomycin prophylaxis for cardiac surgery patients and the risk of
      surgical site infections.
AB  - BACKGROUND: Increased incidence of methicillin-resistant Staphylococcus species
      has required some hospitals to choose vancomycin for surgical prophylaxis.
      Guidelines for appropriate timing of vancomycin prophylaxis state that the
      infusion should begin within 120 min before the first surgical incision. However,
      no studies have investigated the proper timing of vancomycin prophylaxis in
      relationship to surgical site infections (SSI). The objective of the present
      study was to assess the effect of vancomycin prophylaxis timing in relation to
      the first surgical incision on the incidence of SSI. METHODS: We prospectively
      monitored vancomycin prophylaxis timing and incidence of SSI in 2048 patients
      undergoing coronary bypass graft or valve replacement surgery. The timing of
      vancomycin was categorized into five groups based on the relation between the
      start of the infusion and the surgical cut time. Study hypotheses were tested
      using logistic analysis and further validated using a Heckman two-stage model.
      RESULTS: The incidence of SSI were lowest in the 176 patients given vancomycin
      between 16 and 60 min before the surgical incision (3.4%) compared with 15
      patients given vancomycin between 0 and 15 min [26.7%; relative risk (RR): 7.8;
      95% CI: 2.5-24.7], 888 patients given vancomycin between 61 and 120 min (7.7%;
      RR: 2.2; 95% CI: 0.99-5.09), 700 patients given vancomycin between 121 and 180
      min (6.9%; RR: 2.0; 95% CI: 0.87-4.62) or 269 patients given vancomycin >180 min
      (7.8%; RR: 2.3; 95% CI: 0.94-5.56) (P = 0.0119 by chi(2) analysis). Stepwise
      logistic regression analysis and a Heckman two-stage model confirmed that
      vancomycin administration between 16 and 60 min before the first surgical
      incision was associated with the lowest incidence of SSI. CONCLUSIONS: Vancomycin
      administration within 16-60 min before the first surgical incision reduced the
      risk of SSI in cardiac surgery patients.

PMID- 16807255
TI  - High genetic diversity vs. low genetic differentiation in Nouelia insignis
      (Asteraceae), a narrowly distributed and endemic species in China, revealed by
      ISSR fingerprinting.
AB  - BACKGROUND AND AIMS: Nouelia insignis Franch., a monotypic genus of the
      Asteraceae, is an endangered species endemic in Yunnan and Sichuan Provinces of
      China. Most of the populations are seriously threatened. Some of them are even at
      the brink of extinction. In this study, the genetic diversity and differentiation
      between populations of this species were examined in two drainage areas. METHODS:
      DNA fingerprinting based on inter-simple sequence repeat polymorphisms was
      employed to detect the genetic variation and population structure in the species.
      KEY RESULTS: Genetic diversity at species level was high with P=65.05%
      (percentage of polymorphic loci) and Ht=0.2248 (total genetic diversity). The
      coefficient of genetic differentiation among populations, Gst, which was
      estimated by partitioning the total gene diversity, was 0.2529; whereas, the
      genetic differentiation between populations in the Jinsha and Nanpan drainage
      areas was unexpectedly low (Gst=0.0702). CONCLUSIONS: Based on the genetic
      analyses of the DNA fingerprinting, recent habitat fragmentation may not have led
      to genetic differentiation or the loss of genetic diversity in the rare species.
      Spatial apportionment of fingerprinting polymorphisms provides a footprint of
      historical migration across geographical barriers. The high diversity detected in
      this study holds promise for conservation and restoration efforts to save the
      endangered species from extinction.

PMID- 16807256
TI  - The floral scales in Hellmuthia (Cyperaceae, Cyperoideae) and Paramapania
      (Cyperaceae, Mapanioideae): an ontogenetic study.
AB  - BACKGROUND AND AIMS: In 1976 the monotypic genus Hellmuthia was placed in the
      Hypolytreae s.l., but was subsequently ascribed to the Mapanioideae, tribe
      Chrysitricheae, mainly because of the presence in Hellmuthia of two lateral,
      mapanioid-like floral scales with ciliated keels, the anatomy of the nutlet, the
      embryo and the inflorescence. Recently, based on cladistic analyses and supported
      by pollen ontogenetic evidence, Hellmuthia was transferred to a Cyperaceae, tribe
      Cypereae, clade mainly consisting of Ficinia and Isolepis. In this study, the
      floral ontogeny in Hellmuthia was investigated and compared with the floral
      ontogeny in Paramapania, with special attention for the floral scales. METHODS:
      Freshly collected inflorescences of Hellmuthia membranacea and Paramapania
      parvibractea were investigated using scanning electron and light microscopy. KEY
      RESULTS: In the conical 'spikelet' in Hellmuthia, proximal bracts occur, each
      axillating an axis with empty glume-like structures, or a reduced spikelet.
      Hence, it is a reduced partial inflorescence. In Hellmuthia, the stamen primordia
      originate before the primordia of the perianth-gynoecium appear. Moreover, a
      third adaxially positioned 'floral scale' was observed for the first time. The
      position and relative time of appearance of the floral scales in Hellmuthia are
      typical for perianth parts in Cyperoideae. The basal position of Hellmuthia
      within a clade of species with usually perianthless flowers, allows the presence
      of rudiments of a perianth in Hellmuthia to be interpreted as a primitive state.
      Development of the lateral 'scales' in Paramapania follows a different pattern.
      Therefore, it was decided that the lateral 'scales' in Paramapania are different
      from the lateral perianth parts in Hellmuthia. The pollen grains in Hellmuthia
      are cyperoid, with one polar and five lateral apertures, of which the membrane is
      covered with sexinous bodies. The pollen surface is granulate and perforate with
      microspines. CONCLUSIONS: The floral ontogeny in Hellmuthia occurs according to
      the general cyperoid pattern. The lateral scales in Hellmuthia are perianth
      parts, and they are not homologous to the lateral 'scales' in Paramapania.

PMID- 16807257
TI  - Effectiveness and acceptability of lidocaine spray in reducing perineal pain
      during spontaneous vaginal delivery: randomised controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness and acceptability of a lidocaine spray
      in reducing perineal pain during spontaneous vaginal delivery. DESIGN: Randomised
      controlled trial. SETTING: Consultant led obstetric unit. PARTICIPANTS: 185 women
      who had a spontaneous vaginal delivery without epidural analgesia. INTERVENTIONS:
      Topically applied local anaesthetic spray (93 women) and placebo spray (92
      women). MAIN OUTCOME MEASURE: Primary outcome measure was pain during delivery (0
      100 scale). The 16 secondary outcome measures included second degree perineal
      trauma during delivery, trauma of the genital tract, and dyspareunia by two
      months. RESULTS: Lidocaine spray did not reduce pain during spontaneous vaginal
      delivery: mean 77 and 72 on a scale of 0-100 in the lidocaine and placebo groups,
      respectively (difference between means 4.8, 95% confidence interval -1.7 to
      11.2). Lidocaine spray may reduce genital tract trauma during delivery, in
      particular second degree perineal trauma. The intervention was highly acceptable
      to the women and midwives. CONCLUSIONS: Although lidocaine spray applied to the
      perineum during spontaneous vaginal delivery did not reduce perineal pain, it was
      acceptable to both the women and the midwives. TRIAL REGISTRATION: Current
      controlled trials ISRCTN99732966 [controlled-trials.com].

PMID- 16807258
TI  - Potential misclassification of causes of death from COPD.
AB  - Little is known about causes of death in chronic obstructive pulmonary disease
      (COPD) and the validity of mortality statistics in COPD. The present authors
      examined causes of death using data from the Copenhagen City Heart Study. Of the
      12,979 subjects with sufficient data from the baseline examination during 1976
      1978, 6,709 died before 2001. Of these, 242 died with COPD as cause of death.
      Among subjects with at least severe COPD at baseline, only 24.9% had COPD as
      cause of death and, in almost half of the cases where COPD was listed as cause of
      death, the subject had a normal forced expiratory volume in one second /forced
      vital capacity ratio at baseline. In COPD patients, having COPD on the death
      certificate was associated with chronic mucus hypersecretion (CMH) at baseline,
      an odds ratio (OR) of 3.6 (95% confidence interval 1.7-7.7), and being female (OR
      2.7 (1.3-5.6)). In subjects without COPD, CMH and smoking were predictors of COPD
      as underlying cause of death, ORs 2.3 (1.5-3.7) and 2.2 (1.4-3.6), respectively.
      It was concluded that chronic obstructive pulmonary disease is underreported on
      death certificates, that biases in the use of chronic obstructive pulmonary
      disease as cause of death can be assessed, and that possible "over-diagnosis" of
      chronic obstructive pulmonary disease on death certificates in subjects unlikely
      to have significant disease should initiate caution when using causes of
      mortality in chronic obstructive pulmonary disease epidemiology.

PMID- 16807259
TI  - Nontuberculous mycobacteria in bronchiectasis: Prevalence and patient
      characteristics.
AB  - The aim of the current study was to investigate the prevalence and clinical
      associations of nontuberculous mycobacteria (NTM) in a well-characterised cohort
      of patients with adult-onset bronchiectasis. The sputum of all patients attending
      a tertiary referral bronchiectasis clinic between April 2002 and August 2003 was
      examined for mycobacteria as part of an extensive diagnostic work-up. NTM
      positive patients subsequently had further sputa examined. A modified
      bronchiectasis scoring system was applied to all high-resolution computed
      tomography (HRCT) scans from NTM-positive patients, and a matched cohort without
      NTM. Out of 98 patients attending the clinic, 10 had NTM in their sputum on first
      culture; of those, eight provided multiple positive cultures. Three patients were
      treated for NTM infection. A higher proportion of NTM-positive than -negative
      patients were subsequently diagnosed with cystic fibrosis (two out of nine versus
      two out of 75). On HRCT scoring, more patients in the NTM-positive group had
      peripheral mucus plugging than in the NTM-negative group. In the current
      prospective study of a large cohort of patients with bronchiectasis, 10% cultured
      positive for nontuberculous mycobacteria in a random clinic sputum sample. Few
      clinical parameters were helpful in discriminating between groups, except for a
      higher prevalence of previously undiagnosed cystic fibrosis and of peripheral
      mucus plugging on high-resolution computed tomography in the nontuberculous
      mycobacteria group.

PMID- 16807260
TI  - Clinical evaluation of a screen pneumotachograph as an in-line filter.
AB  - The American Thoracic Society/European Respiratory Society Task Force underlined
      that the use of in-line filters during respiratory function tests "is an area of
      controversy". The aim of the present study was to measure the contamination
      occurring during forced expiration downstream from a screen pneumotachograph (SP)
      with and without an in-line filter (Pall PF30S). A total of 40 healthy subjects
      performed eight consecutive maximal expiratory manoeuvres into four sterile
      apparatuses (A1: no filter, no SP; A2: filter-only; A3: SP-only; A4: filter and
      SP) in random order. A blood agar plate was fixed downstream from the apparatus.
      Colony-forming units (CFUs) were counted after 24 h incubation at 37 degrees C.
      Of the 40 plates obtained with each apparatus, 13 were sterile with A1 (range 0
      679 CFUs), 25 with A2 (0-49 CFUs), 30 with A3 (0-35 CFUs) and 39 with A4 (one CFU
      in the only positive plate). A1 versus A2 and also A3 versus A4 gave different
      values for the CFU number, but A2 and A3 showed similar contamination levels. The
      authors conclude that: 1) the in-line filter does not perform better than a
      screen pneumotachograph; 2) it does not eliminate the need to decontaminate the
      pneumotachograph; and 3) equipment placed downstream from an in-line filter and a
      screen pneumotachograph is almost protected from contamination.

PMID- 16807261
TI  - Physical activity is independently related to aerobic capacity in cystic
      fibrosis.
AB  - It is unclear whether a relationship between physical activity (PA) and maximal
      oxygen uptake (V'(O2,max)) exists in cystic fibrosis (CF) and, if so, whether the
      relationship reflects a direct effect or is mediated by the effects of
      confounding variables, such as pulmonary or muscle function. The objective of the
      present study was to determine the relationship between PA and V'(O2,max) in CF
      while adjusting for possible influences of confounding factors. In total, 36
      female and 35 male patients with CF from Germany and Switzerland (aged 12-40 yrs,
      forced expiratory volume in one second (FEV1) 25-107% predicted) were studied. A
      Wingate test was employed to measure muscle power. PA was monitored for 7 days
      and expressed in two ways: 1) average daily accelerometer count (ADAC) and 2)
      time spent in moderate-to-vigorous PA (MVPA). V'(O2,max) was determined during an
      incremental cycle exercise test to volitional fatigue. PA was positively related
      to V'(O2,max). In a multiple linear regression analysis, height, sex, FEV1,
      muscle power and ADAC (additionally explained variance 2.5%) or time spent in
      MVPA (additionally explained variance 3.7%) were identified as independent
      predictors of V'(O2,max). In conclusion, high levels of physical activity in
      addition to good muscular and pulmonary functions are associated with a high
      aerobic capacity in cystic fibrosis.

PMID- 16807262
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes
      in the radiologically normal mediastinum.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can
      sample enlarged mediastinal lymph nodes in patients with nonsmall cell lung
      cancer (NSCLC). To date, EBUS-TBNA has only been used to sample nodes visible on
      computed tomography (CT). The aim of the present study was to determine the
      accuracy of EBUS-TBNA in sampling nodes <or=1 cm in diameter. NSCLC patients with
      CT scans showing no enlarged lymph nodes (no node >1 cm) in the mediastinum
      underwent EBUS-TBNA. Identifiable lymph nodes at locations 2r, 2l, 4r, 4l, 7,
      10r, 10l, 11r and 11l were aspirated. All patients underwent subsequent surgical
      staging. Diagnoses based on aspiration results were compared with those based on
      surgical results. In 100 patients (mean age 58.9 yrs; 68 males), 119 lymph nodes
      ranging 5-10 mm in size were detected and sampled. Malignancy was detected in 19
      patients but missed in two; all diagnoses were confirmed by surgical findings.
      The mean diameter of the punctured lymph nodes was 8.1 mm. The sensitivity of
      EBUS-TBNA for detecting malignancy was 92.3%, specificity was 100%, and the
      negative predictive value was 96.3%. No complications occurred. In conclusion,
      endobronchial ultrasound-guided transbronchial needle aspiration can accurately
      sample even small mediastinal nodes, therefore avoiding unnecessary surgical
      exploration in one out of six patients who have no computed tomography evidence
      of mediastinal disease. Potentially operable patients with no signs of
      mediastinal involvement on computed tomography may benefit from pre-surgical
      endobronchial ultrasound-guided transbronchial needle aspiration and staging.

PMID- 16807263
TI  - Anti-inflammatory cytokines in cystic fibrosis lung disease.
AB  - Lung inflammation plays a pivotal role in the pathogenesis of airway disease in
      cystic fibrosis (CF). An imbalance between pro- and anti-inflammatory mediators
      has been observed and a deficiency in the anti-inflammatory response has been
      proposed, but this concept remains controversial. In the present study, the
      concentrations of two anti-inflammatory mediators, lipoxin A (LxA4) and Clara
      cell protein 10 (CC-10), were assessed in bronchoalveolar lavage fluid (BALF) of
      CF patients with a wide range of endobronchial inflammation and disease controls
      with neutrophilic inflammation unrelated to CF. No differences were observed in
      LxA4 BALF concentrations between CF patients and controls with a similar degree
      of neutrophilic airway inflammation. Concentrations were also similar in CF
      patients with mild versus more severe airway inflammation. In contrast, CC-10
      concentrations were lower in CF patients, but this decrease was limited to
      patients with more intense airway inflammation. The present data do not support
      the concept of a primary defect in anti-inflammatory mediators in cystic fibrosis
      lung disease. Although Clara cell protein concentrations were found to be
      reduced, these alterations appear to be secondary to neutrophilic airway
      inflammation rather than due to a primary deficiency.

PMID- 16807264
TI  - Healthcare workers with tuberculosis infected during work.
AB  - The risk for healthcare workers (HCWs) of tuberculosis (TB) attributable to
      occupational exposure is difficult to determine, as are the conditions
      contributing to this risk. The objective of the present study was to determine
      which TB cases among HCWs in the Netherlands were infected during work and to
      analyse factors which contributed to infection and subsequent disease. The total
      study population consisted of 101 cases over a 5-yr period. In 67 (66%) subjects
      the route of infection could be determined by epidemiological and microbiological
      information. Of these cases, 28 out of 67 (42%) were due to infection at work, 19
      (28%) were community acquired, and 20 (30%) were infected abroad. The 28 cases
      infected at work were subject to an in-depth analysis. Delayed diagnosis of the
      index case, especially in the elderly patient, was the main cause of patient-to
      HCW transmission. In some circumstances, inadequate infection-control measures
      also contributed to transmission. In conclusion, a high suspicion of tuberculosis
      by the clinician, adequate infection control measures by hospital authorities,
      and early identification of latent tuberculosis infection by occupational and
      public-health specialists are necessary to prevent tuberculosis among healthcare
      workers.

PMID- 16807265
TI  - Sildenafil treatment for portopulmonary hypertension.
AB  - Portopulmonary hypertension (POPH) is regarded as a subtype of pulmonary arterial
      hypertension (PAH); however, established PAH therapies have not been evaluated
      for this condition. The current authors treated 14 patients (four male, 10
      female; mean (range) age 55 (39-75) yrs) with moderate (n = 1) or severe (n = 13)
      POPH caused by alcoholic liver disease (n = 7), chronic viral hepatitis (n = 3),
      autoimmune hepatitis (n = 3), and hepatic manifestation of hereditary
      haemorrhagic teleangiectasia (n = 1) with oral sildenafil. Eight patients were
      newly started on pulmonary vasoactive treatment, while six patients were already
      on treatment with inhaled prostanoids (iloprost, n = 5; treprostinil, n = 1).
      During treatment with sildenafil, mean +/- sd 6-min walk distance increased from
      312 +/- 111 m to 397 +/- 99 m after 3 months, and 407 +/- 97 m after 12 months.
      Mean +/- sd pro-brain natriuretic peptide levels decreased from 582 +/- 315 ng x
      mL(-1) to 230 +/- 278 ng x mL(-1), and to 189 +/- 274 ng x mL(-1) after 3 and 12
      months, respectively. Two patients died after 1 and 2 months from liver failure
      and cardiac failure, respectively. There was a similar response to sildenafil
      treatment after 3 and 12 months in patients on monotherapy and those on
      combination therapy. In conclusion, sildenafil might be effective in monotherapy
      and in combination therapy with inhaled prostanoids in portopulmonary
      hypertension, leading to significant improvement by 3 months and sustained
      response over 12 months.

PMID- 16807267
TI  - How is difficult asthma managed?
AB  - Most patients with asthma can be easily treated. Some have difficult asthma; in
      some because the diagnosis is erroneous, in others because of comorbidity or
      noncompliance. A European Respiratory Society Task Force has called for an
      integrated approach for these patients, and positive results have been reported
      using protocols. In the UK, there is no overall understanding of the size of this
      problem, or how these patients are managed. A postal survey of 683 consultant
      members of the British Thoracic Society designed to elicit respondents' views on
      how they would manage four clinical scenarios was conducted. There was a 50.4%
      response rate. Few reported a uniform approach to the investigation of such
      patients. The availability of allied healthcare professionals was variable. The
      21 consultant respiratory physicans, reporting a special interest in difficult
      asthma, were significantly more likely to objectively assess compliance, perform
      skin-prick tests and to utilise a liaison psychiatrist than those without an
      expressed special interest in asthma. Many reported difficulty in accessing
      psychologists, liaison psychiatrists and social workers. Approaches to the
      diagnosis and management of "vocal cord dysfunction" were variable. The results
      of this postal survey of specialist thoracic physicians in the UK suggest that a
      protocol for difficult asthma is not in widespread use and that access to
      necessary allied healthcare professionals is not uniform. Pulmonologists with a
      declared special interest in difficult asthma may have configured their services
      and approaches more in line with that proposed by the European Respiratory
      Society Task Force.

PMID- 16807266
TI  - Phosphodiesterase 4 inhibition of beta2-integrin adhesion caused by leukotriene
      B4 and TNF-alpha in human neutrophils.
AB  - Phosphodiesterase (PDE)4 inhibition attenuates neutrophilic inflammation in
      chronic obstructive pulmonary disease. The objective of the present study was to
      examine the efficacy and mechanism by which PDE4 inhibition blocks adhesion of
      beta(2)-integrin to an endothelial counterligand. Neutrophils (polymorphonuclear
      leukocytes (PMNs)) were isolated from humans receiving no medication. Adhesion
      was analysed by myeloperoxidase activity. The effects of cilomilast+/-salmeterol
      on the following were determined: 1) surface CD11b expression; 2) adhesion; 3)
      intracellular cyclic adenosine monophosphate (cAMP) concentration; and 4)
      extracellular signal-regulated kinase (ERK)-1/2-mediated group IVA-phospholipase
      A(2) (gIVA-PLA(2)) phosphorylation caused by leukotriene (LT)B(4) or tumour
      necrosis factor (TNF)-alpha activation. Either cilomilast or rolipram+/
      salmeterol caused concentration-related blockade of LTB(4)-induced adhesion to
      counterligand, but had no effect on TNF-alpha-activated PMNs. A comparable
      increase in intracellular cAMP concentration for PMNs activated with LTB(4) and
      TNF-alpha was caused by 1 muM cilomilast and 0.1 microM salmeterol. Upregulation
      of surface CD11b expression and ERK-1/2 phosphorylation were blocked by
      cilomilast or rolipram+/-salmeterol for PMNs activated by LTB(4), but not for
      cells stimulated by TNF-alpha. Cilomilast+/-salmeterol also blocked gIVA-PLA(2)
      phosphorylation caused by LTB(4) but not TNF-alpha. In conclusion, the current
      study demonstrates that both leukotriene B(4) and tumour necrosis factor-alpha
      upregulate cyclic adenosine monophosphate. However, cyclic adenosine
      monophosphate does not block beta(2)-integrin adhesion caused by tumour necrosis
      factor-alpha. It was concluded that tumour necrosis factor-alpha prevents
      inhibition of extracellular signal-regulated kinase-1/2-mediated group IVA
      phospholipase A(2) activation, which is essential for beta(2)-integrin adhesion
      in polymorphonuclear leukocytes.

PMID- 16807268
TI  - Tuberculosis outbreak among students in a boarding school.
AB  - Tuberculosis (TB) outbreaks present a public health challenge. Six cases of
      active TB emerged in a boarding school in Israel during 1 yr. An epidemiological
      outbreak investigation was performed, followed by implementation of control
      measures. The investigation included interviews, tuberculin skin test (TST) and
      chest radiographs of the students. Close contact (n = 155) was defined as being
      in the same class or dormitory with a patient. Remote contact (n = 246) was
      defined as being in the school. An epidemiological association was detected among
      five of the cases and a distinct pattern was found in molecular analysis. TST was
      performed in 398 (99.2%) students. Repeated (two-step) TST was applied to the
      close contacts. The degree of contact, country of origin and previous bacille
      Calmette-Guerin vaccination were significantly associated with TST reactions.
      Preventive directly observed therapy was completed by 157 (91.3%) students.
      During 5 yrs follow-up, no additional cases emerged. While investigating a
      tuberculosis outbreak, the definition of degree of contact is a significant
      predictor for detecting positive tuberculin test. Immigration from an endemic
      country, as well as previous bacille Calmette-Guerin vaccination have a major
      effect on tuberculin skin-test results. The directly observed therapy approach
      was found to be successful in preventing further morbidity.

PMID- 16807269
TI  - Trends in imported childhood malaria in the UK: 1999-2003.
AB  - OBJECTIVE: To describe the epidemiology of imported malaria in children in the
      UK. METHODS: Surveillance data on children with imported malaria, collected
      through an enhanced surveillance network set up by the Malaria Reference
      Laboratory (London, UK), diagnosed between January 1999 and December 2003 were
      analysed. RESULTS: Over the 5-year study period, 9238 cases were reported to the
      Malaria Reference Laboratory, and children accounted for 1456 (14.8%) cases. The
      number of imported paediatric malaria cases fell from 326 in 1999 to 241 in 2003.
      Malarial infection occurred in children of all ages and the number of patients
      increased gradually with age. Visiting family and relatives was the most common
      reason for travel (59.5%), with only 7.2% travelling to an area endemic to
      malaria on holiday. Most infections (88.4%) were acquired in Africa, and mainly
      in Nigeria (49.7%). Plasmodium falciparum was responsible for 81.7% of all cases,
      followed by P. vivax (11.1%). The number of both P. falciparum and P. vivax cases
      fell gradually from 262 and 45 cases in 1999 to 196 and 20 cases in 2003,
      respectively. Malaria prophylaxis was taken by 39% of 500 children with malaria
      who had travelled to a country endemic to malaria. The proportion of children
      with malaria who had taken malaria prophylaxis decreased steadily from 53% in
      1999 to 29% in 2003. Two (0.14%) children died compared with 62 (0.76%) adults
      over the 5-year study period (p = 0.007). CONCLUSIONS: Although the incidence of
      malaria has started to decline, a considerable number of children are still
      diagnosed with malaria in the UK. In addition, the proportion of children with
      malaria who had taken malaria prophylaxis is falling. Although it is reassuring
      to note the low mortality, there is an urgent need to improve preventive measures
      among families travelling to high-risk countries.

PMID- 16807270
TI  - Hearts with concordant ventriculoarterial connections but parallel arterial
      trunks.
AB  - OBJECTIVES: To determine the characteristic morphological features of hearts with
      concordant ventriculoarterial connections and parallel arterial trunks, and to
      provide unequivocally a method to describe their anatomy. DESIGN, METHODS AND
      PATIENTS: The entire cardiac database and cardiac pathological archive at the
      Hospital for Sick Children, Toronto, Ontario, Canada, was interrogated to
      identify all patients with concordant ventriculoarterial connections and parallel
      arterial trunks. The clinical records, autopsy reports and actual cardiac
      specimens of those who underwent autopsy, were reviewed. RESULTS: 8 cases meeting
      our criteria were identified. The infundibular anatomy was variable, including
      four hearts with bilateral infundibulums, three with subpulmonary infundibulums
      and one with bilaterally absent infundibulums. Considerable variability was also
      found in the type of atrial arrangement, along with the morphology of the
      atrioventricular junctions. The most common findings were the usual atrial
      arrangement (n = 5), left juxtaposition of the right atrial appendages (n = 3),
      an atrial septal defect (n = 6), univentricular atrioventricular connection (n =
      5), ventricular septal defect (n = 8) and pulmonary obstruction (n = 4). In
      addition, five specimens had either a single coronary artery or two coronary
      arteries arising from the anticipated right coronary aortic sinus. CONCLUSIONS:
      Concordant ventriculoarterial connections with parallel arterial trunks can be
      found in a variety of segmental combinations. An accurate diagnosis of these rare
      hearts can be achieved by detailed analysis of not only the ventriculoarterial
      connections but also the infundibular anatomy and the spatial relationship of the
      arterial trunks. Particular attention to the coronary arteries is warranted.

PMID- 16807271
TI  - Impaired endothelium-dependent vascular reactivity in patients with familial
      combined hyperlipidaemia.
AB  - BACKGROUND: Familial combined hyperlipidaemia (FCHL) is associated with a
      markedly increased risk of premature coronary artery disease. This study was
      designed to evaluate whether preclinical atherosclerotic functional abnormalities
      are detectable in the arteries of patients with FCHL. METHODS: 60 subjects were
      recruited for the study: 30 probands of families with FCHL (mean (standard
      deviation (SD)) age 48 (10) years, 77% men), defined by fasting total plasma
      cholesterol or triglyceride concentration >250 mg/dl (>6.5 mmol/l cholesterol,
      >2.8 mmol/l triglyceride) and by the occurrence of multiple lipoprotein
      phenotypes within a family, and 30 age-matched and sex-matched healthy controls.
      All subjects underwent high-resolution B-mode ultrasound examination and the
      brachial arterial reactivity, a marker of endothelial function, was measured by a
      semiautomated computerised program. Lipid profile, resting blood pressure, body
      mass index (BMI), smoking status, insulin and homocysteine levels were also
      determined. RESULTS: Compared with controls, patients with FCHL had significantly
      higher BMI, diastolic blood pressure and insulin levels. No difference was
      observed in baseline brachial diameter between the two groups (mean (SD) 3.45
      (0.51) mm for FCHL v 3.60 (0.63) mm for controls; p = 0.17). In response to flow
      increase, the arteries of the controls dilated (mean (SD) 8.9% (4.9%), range 2.3
      20.8%), whereas in the patients with FCHL, brachial arterial reactivity was
      significantly impaired (5.5% (2.5%), range 0-10.1%; p = 0.002). In multivariate
      linear regression analysis, apolipoprotein B and BMI were independent
      determinants of brachial artery response to reactive hyperaemia. CONCLUSIONS: The
      findings of our study suggest that vascular reactivity is impaired in the
      arteries of patients with FCHL.

PMID- 16807272
TI  - Plasma haemostatic markers, endothelial function and ambulatory blood pressure
      changes with home versus hospital cardiac rehabilitation: the Birmingham
      Rehabilitation Uptake Maximisation Study.
AB  - BACKGROUND: Cardiac rehabilitation is an accepted therapeutic intervention in
      patients after myocardial infarction or coronary revascularisation. The effects
      of cardiac rehabilitation programmes, whether home based or hospital based, on
      haemostatic indices (as reflected by fibrinogen, plasma viscosity, fibrin D-dimer
      (an index of thrombogenesis), von Willebrand factor (vWf, an index of endothelial
      damage/dysfunction), soluble P-selectin (an index of platelet activation)),
      vasomotor function (using flow-mediated dilatation (FMD)) and ambulatory blood
      pressure (ABP) in patients with coronary heart disease are unknown. METHODS: 81
      patients (66 men, mean (SD) 59 (11) years) after myocardial infarction or
      coronary revascularisation were randomised to comprehensive hospital-based (n =
      40) or home-based (n = 41) cardiac rehabilitation. Plasma levels of vWf, D-dimer,
      fibrinogen, soluble P-selectin and plasma viscosity, as well as FMD and 24-h ABP,
      were measured at baseline and after 3 months of cardiac rehabilitation. RESULTS:
      In patients who completed cardiac rehabilitation, levels of vWf, fibrinogen and D
      dimer were significantly lower and FMD improved (all p<or=0.001), whereas levels
      were unchanged in controls. Significant reductions were also observed in 24-h
      mean systolic blood pressure, diastolic blood pressure and mean aortic pressure
      after completion of cardiac rehabilitation (all p<0.05). No significant
      differences were observed between the hospital-based and home-based cardiac
      rehabilitation programmes on these indices. CONCLUSIONS: Cardiac rehabilitation
      improves haemostasis, endothelial function and ABP in patients with coronary
      heart disease, with no significant differences between home-based and hospital
      based cardiac rehabilitation programmes. These effects may contribute to the
      beneficial effects of cardiac rehabilitation programmes on CV outcomes.

PMID- 16807273
TI  - Pathological effects of alcohol septal ablation for hypertrophic obstructive
      cardiomyopathy.
AB  - BACKGROUND: The pathological effects and the mechanisms of action of
      intracoronary administration of ethanol for alcohol septal ablation (ASA) for the
      management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown.
      METHODS: We examined surgical specimens and, in one case, autopsy specimens from
      four patients who underwent surgical septal myectomy 2 days to 14 months after
      unsuccessful ASA. RESULTS: Pathological examination early after ASA showed
      coagulative necrosis of both the myocardium and the septal perforator arteries.
      Affected arteries were distended and occluded by necrotic intraluminal debris,
      without platelet-fibrin thrombi. Late after unsuccessful ASA, excised septal
      tissue was heterogeneous, containing a region of dense scar, and adjacent tissue
      containing viable myocytes and interspersed scar. CONCLUSIONS: Intracoronary
      administration of ethanol in patients with HOCM causes acute myocardial
      infarction with vascular necrosis. The coagulative necrosis of the arteries,
      their distension by necrotic debris and the absence of platelet-fibrin thrombi
      distinguish ethanol-induced infarction from that caused by atherosclerotic
      coronary artery disease. The direct vascular toxicity of ethanol may be an
      important aspect of the mechanism of successful ASA.

PMID- 16807274
TI  - A population study of the long-term consequences of Rose angina: 20-year follow
      up of the Renfrew-Paisley study.
AB  - OBJECTIVE: To examine the long-term cardiovascular consequences of angina in a
      large epidemiological study. DESIGN: Prospective cohort study conducted between
      1972 and 1976 with 20 years of follow-up (the Renfrew-Paisley Study). SETTING:
      Renfrew and Paisley, West Scotland, UK. PARTICIPANTS: 7048 men and 8354 women
      aged 45-64 years who underwent comprehensive cardiovascular screening at
      baseline, including the Rose Angina Questionnaire and electrocardiography (ECG).
      MAIN OUTCOME MEASURES: All deaths and hospitalisations for cardiovascular reasons
      occurring over the subsequent 20 years, according to the baseline Rose angina
      score and baseline ECG. RESULTS: At baseline, 669 (9.5%) men and 799 (9.6%) women
      had angina on Rose Angina Questionnaire. All-cause mortality for those with Rose
      angina was 67.7% in men and 43.3% in women at 20 years compared with 45.4% and
      30.4%, respectively, in those without angina (p<0.001). Values are expressed as
      hazards ratio (HR) (95% confidence interval (CI). In a multivariate analysis, men
      with Rose angina had an increased risk of cardiovascular death or hospitalisation
      (1.49 (1.33 to 1.66), myocardial infarction (1.63 (1.41 to 1.85)) or heart
      failure (1.54 (1.13 to 2.10)) compared with men without angina. The corresponding
      HR (95% CI) for women were 1.38 (1.23 to 1.55), 1.56 (1.31 to 1.85) and 1.92
      (1.44 to 2.56). An abnormality on the electrocardiogram (ECG) increased risk
      further, and both angina and an abnormality on the ECG increased risk most of all
      compared with those with neither angina nor ischaemic changes on the ECG.
      Compared with men, women with Rose angina were less likely to have a
      cardiovascular event (0.54 (0.46 to 0.64)) or myocardial infarction (0.44 (0.35
      to 0.56)), although there was no sex difference in the risk of stroke (1.11 (0.75
      to 1.65)), atrial fibrillation (0.84 (0.38 to 1.87)) or heart failure (0.79 (0.51
      to 1.21)). CONCLUSIONS: Angina in middle age substantially increases the risk of
      death, myocardial infarction, heart failure and other cardiovascular events.

PMID- 16807275
TI  - Screening in women's health, with emphasis on fetal Down's syndrome, breast
      cancer and osteoporosis.
AB  - Screening tests have become increasingly popular in women's health care over the
      last two decades. The initiative for screening is typically generated by either
      an agency or the health care professional being consulted for some reason. In
      many instances, however, the demand for screening tests is patient driven with
      the health care provider being poorly prepared to determine the usefulness of
      screening. This review illustrates the complexity of screening using three
      disorders where early detection and treatment have the potential to improve the
      quality and longevity of life. Prenatal diagnosis of Down's syndrome does not
      offer the parents the opportunity for cure but does offer the opportunity for
      education and rational choice as the impact of the diagnosis on the family is
      weighed. The evidence for breast cancer screening is more persuasive for older
      than younger women, but even in older women, there is a balance of risks and
      benefits. Treatment options for osteoporosis have improved in terms of reductions
      in fracture risk as well as beneficial effects on bone density, but evidence of
      the effectiveness of a screening programme for this condition in an unselected
      population is lacking. Ultimately, it is crucial that women be provided with
      clear and comprehensive information about the screening programme, in terms of
      possible gains but also costs of various kinds: physical, economic and
      psychological.

PMID- 16807276
TI  - Hormones and cardiovascular health in women.
AB  - Cardiovascular diseases (CVDs) may have their origin before birth: the
      combination of being small at birth and having an overly rich post-natal diet
      increases the likelihood of obesity and of acquiring a specific metabolic
      syndrome in adulthood that carries an increased risk of CVD. The incidence of CVD
      and mortality is very low in women of reproductive age but rises to a significant
      level in older women. In this article, we discuss CVD in relation to hormonal
      contraception, pregnancy and polycystic ovarian syndrome (PCOS) in younger women
      and menopause in older women. Women with PCOS have a higher risk of diabetes and
      hypertension, but studies to date have not shown an effect on CVD events. Use of
      combined hormonal contraception has only small effects on CVD because of the low
      baseline incidence of myocardial infarction (MI), stroke and venous
      thromboembolism (VTE) among young women. Women with existing risk factors or
      existing CVD, however, should consider alternative contraception. In pregnancy,
      CVD is rare, although, in the West, it now accounts for a significant proportion
      of maternal mortality as the frequency of obstetrical causes of mortality has
      substantially declined. The frequency of VTE is 15 per 10,000 during pregnancy
      and the post-partum period. In older women, menopause causes a slightly higher
      risk of MI after allowing for age, although there is substantial heterogeneity in
      the results of studies on menopause and age at menopause and MI. A larger effect
      might have been expected, because estrogen reduces the risk of developing
      atherosclerosis in premenopausal women, whereas in post-menopausal women who may
      have established atherosclerotic disease, estrogen increases the risk of
      myocardial disease through the effects on plaque stability and clot formation.
      Recent trial results indicate that hormone treatment in menopause does not
      favourably affect the risk of MI, stroke or other vascular disease. Thus,
      prevention of CVD should rely on diet and fitness, low-dose aspirin and treatment
      of hypertension, hyperglycaemia and hyperlipidaemia.

PMID- 16807277
TI  - Cavotricuspid isthmus angiography predicts atrial flutter ablation efficacy in
      281 patients randomized between 8 mm- and externally irrigated-tip catheter.
AB  - AIMS: Radiofrequency ablation (RFA) of cavotricuspid isthmus (CTI)-dependent
      atrial flutter can be performed using various types of ablation catheters. Recent
      evaluations comparing externally cooled-tip RFA (ecRFA) catheters and large-tip
      (8 mm) catheters found that ecRFA catheter may have a higher efficacy for CTI
      ablation. The aim of this prospective study was to compare both catheters by
      stratifying on CTI morphology in order to explain, in part, the discrepancies
      between previous randomized studies, and to validate predictive factors of
      difficult CTI ablation on clinical, echocardiographic, and angiographic data.
      METHODS AND RESULTS: Over a period of 24 months, 281 patients were included and
      stratified on CTI morphology: 'straight', 'concave', and 'pouch-like recess'. In
      straight CTI (n=150), the duration of application time with a median of 6 min
      [interquartile range (IQR) 4-9] vs. a median of 12 min (IQR 16-19; P<0.0001) and
      the duration of X-ray exposure with a median of 6 min (IQR 4.4-9.7) vs. a median
      of 10.4 min (IQR 7-17; P<0.0001) were significantly lower with an 8 mm-tip when
      compared with ecRFA catheter. In contrast, in concave CTI (n=95), a trend towards
      both shorter application time with a median of 12.5 min (IQR 6-23) vs. a median
      of 19 min (IQR 7-28; P=0.08) and X-ray duration exposure with a median of 10.4
      min (IQR 6-20) vs. a median of 13 min (IQR 8-24; P=0.08) with an ecRFA catheter
      when compared with 8 mm-tip catheter were evidenced. No significant difference
      was shown between 8 mm-tip and ecRFA catheters in the pouch-like recess group
      (n=36). Predictive factors of difficult ablation include right CTI length and
      morphology. CONCLUSION: This study demonstrates that the 8 mm-tip catheter is
      more effective for ablation in case of a straight angiographic isthmus morphology
      and that the ecRFA catheter tends to be more effective in case of concave
      angiographic isthmus morphology. Thus, angiographic isthmus evaluation may
      predict both the effectiveness of an RF catheter, and the risk of an expensive
      crossover. These data may explain, in part, the discrepancies of previous studies
      comparing both catheters.

PMID- 16807278
TI  - Mifepristone-induced amenorrhoea is associated with an increase in microvessel
      density and glucocorticoid receptor and a decrease in stromal vascular
      endothelial growth factor.
AB  - BACKGROUND: We have previously shown that the progesterone antagonist
      mifepristone is a contraceptive when given in a dose of 2 or 5 mg per day. The
      majority of women experience amenorrhoea rather than the irregular break through
      bleeding usually occurring with other estrogen-free contraceptive pills, such as
      progestogen-only pill (POP). We investigated the effects of low-dose mifepristone
      on endometrial parameters which may be associated with changes in endometrial
      function, such as microvasculature, vascular endothelial growth factor (VEGF) and
      glucocorticoid receptor (GR) content. METHODS AND RESULTS: Endometrial biopsies
      were collected from 16 women before (late proliferative phase) and 60 and 120
      days after taking 2 or 5 mg mifepristone daily for 120 days. Seven of the eight
      women who received 2 mg mifepristone and all eight women who received 5 mg were
      amenorrhoeic during the study. Mean estradiol (E(2)) concentrations remained in
      the mid-proliferative range, and the majority (9/16) of women showed
      proliferative endometrial histology at 60 and 120 days following treatment. There
      was a significant increase in the density of the endometrial stroma (P < 0.05)
      and microvessels (P < 0.01) following 120 days of treatment. Immunocytochemistry
      showed that GR, hitherto localized specifically in endometrial stroma, was up
      regulated in the nuclei of glands (P < 0.05) and surface (luminal) epithelium (P
      < 0.01) by 60 days and maintained at 120 days. There was a significant reduction
      in stromal VEGF protein expression by day 120 of treatment (P < or = 0.01).
      CONCLUSION: The high incidence of amenorrhoea in women taking mifepristone may be
      related to changes in the regulation of vascular function.

PMID- 16807279
TI  - The normal human myometrium has a vascular spatial gradient absent in small
      fibroids.
AB  - BACKGROUND: The human uterine vasculature is highly structured, exhibiting
      circumferential and radial branching. Previously published angiograms of the
      arterial network describe a system of regular coils. Uterine fibroids lack this
      structured vasculature. In this study, we make a comparison between the
      vasculature in normal myometrium and in fibroids using robust stereological
      methods thus far lacking in the literature. METHODS: Stereological and
      morphometric analysis of the vascular system was carried out on 15 normal and 27
      small fibroid (5-40 mm) uteri taken from women suffering menorrhagia. Projected
      images of published angiograms were also re-examined, measuring tortuosity.
      RESULTS: A decreasing gradient of vascular smooth muscle from outer to inner
      myometrium was found in normal uteri, with no corresponding gradient in capillary
      tissue fraction. An association between vascular luminal size, amplitude and
      frequency of vessel bending was also established. Conversely, fibroids were found
      to lack structured or muscularized vasculature. CONCLUSIONS: A quantitative
      gradient within the myometrial vascular system, which is absent in fibroids, has
      been demonstrated. These structural differences between diseased and healthy
      tissues are probably because of differing expression of angiogenic growth factors
      and may explain the distribution of particles seen after uterine artery
      embolization.

PMID- 16807280
TI  - MUC4 gene polymorphism and expression in women with implantation failure.
AB  - INTRODUCTION: The molecular mechanism of human embryo implantation is poorly
      understood. The role of MUC4 mucin, present in endometrial epithelium, has never
      been explored, and results obtained in animal studies strongly suggest a role in
      implantation. We investigated the role of MUC4 in human embryo implantation.
      METHODS AND RESULTS: We analysed the MUC4 variable number of tandem repeat (VNTR)
      polymorphism in three populations by Southern blot analysis: spontaneously
      fertile patients (C), infertile patients with repeated unexplained implantation
      failures after IVF (IF) and patients with a child after IVF (IVF-C). We found no
      differences in the size or allelic distribution of MUC4 VNTR between these three
      populations. We also examined, in IVF-C and IF groups, the endometrial expression
      of MUC4 mRNA as well as the expression of the MUC4 glycoprotein together with
      estrogen receptor (ER) and progesterone receptor (PR). No expression differences
      could be detected. However, we noticed a pattern of expression for MUC4 protein,
      which is limited to patches of cells in the luminal and glandular epithelium.
      CONCLUSIONS: We conclude that the different-sized MUC4 alleles do not interfere
      with implantation. The absence of coexpression of MUC4 and the steroid receptors
      suggests that MUC4 expression is not directly regulated by steroids.

PMID- 16807281
TI  - Differential effects of oral conjugated equine estrogen and transdermal estrogen
      on atherosclerotic vascular disease risk markers and endothelial function in
      healthy postmenopausal women.
AB  - BACKGROUND: Recent studies have revealed that HRT may increase the risk for
      atherosclerotic vascular disease (ASVD). METHODS: We investigated the effects of
      HRT via different administration routes on the markers for ASVD and endothelial
      function in healthy postmenopausal women. The oral HRT group (n=18) received
      conjugated equine estrogen 0.625 mg/day; the transdermal HRT group (n=18)
      received 17beta-estradiol (E2) gel 0.6 mg/day for 6 months. The control group
      (n=30) had no treatment for 6 months. RESULTS: The C-reactive protein (CRP) rose
      from 0.129+/-0.116 to 0.752+/-0.794 mg/dl (P<0.01) in the oral HRT group but
      remained unchanged in the transdermal HRT and control groups. The flow-mediated
      vasodilation (FMD) in the brachial artery was increased significantly by HRT from
      6.0% before oral HRT to 14.7% after oral HRT (P<0.001) and from 5.9% before
      transdermal HRT to 13.9% after transdermal HRT (P=0.001). CONCLUSIONS: These data
      suggest that oral estrogen induces ASVD risk by increasing acute inflammation;
      however, transdermal estrogen avoids this untoward effect. Additionally,
      transdermal estrogen exerts a positive effect on endothelial function similar to
      that of oral estrogen. Therefore, the transdermal route might be favourable in
      terms of ASVD risks.

PMID- 16807282
TI  - The effects of oxygen concentration and gestational age on extravillous
      trophoblast outgrowth in a human first trimester villous explant model.
AB  - BACKGROUND: In the first trimester of human pregnancy, extravillous trophoblasts
      from placental villi invade the decidua temporarily occluding the spiral
      arteries, preventing maternal blood flow and creating a low-oxygen environment,
      which is believed to play an important role in the regulation of extravillous
      trophoblast outgrowth. This work aimed to quantify the effects of gestational age
      and oxygen concentration on extravillous trophoblast outgrowth. METHODS: A
      quantitative first trimester villous explant model was used to measure the
      frequency and area of extravillous trophoblast outgrowths from villi grown in 1.5
      or 8% oxygen. RESULTS: The percentage of explants producing outgrowth declined
      independently of oxygen concentration as gestation increased from 8 to 12 weeks.
      Culture in 1.5% oxygen significantly reduced the frequency and area of outgrowths
      in comparison with 8% oxygen. HLA-G and alpha1 integrin were both expressed
      throughout outgrowths, with no difference in the expression between oxygen
      concentrations. Gestation influenced the response of explants to oxygen, with a
      significant differential response to oxygen concentration in placentae under 11
      weeks of gestation, whereas in villi from placentae of 11 or 12 weeks, no
      differential response was observed. CONCLUSIONS: In the first trimester, oxygen
      and gestational age both regulate extravillous trophoblast outgrowth.

PMID- 16807283
TI  - The colloidal thyroxine (T4) ring as a novel biomarker of perchlorate exposure in
      the African clawed frog Xenopus laevis.
AB  - The purpose of this study was to determine if changes in colloidal thyroxine
      (T(4)) immunoreactivity can be used as a biomarker of perchlorate exposure in
      amphibian thyroid tissue. Larval African clawed frogs (Xenopus laevis) were
      exposed to 0, 1, 8, 93, and 1131 microg perchlorate/l for 38 and 69 days to cover
      the normal period of larval development and metamorphosis. The results of this
      study confirmed the presence of an immunoreactive colloidal T(4) ring in thyroid
      follicles of X. laevis and demonstrated that the intensity of this ring is
      reduced in a concentration-dependent manner by perchlorate exposure. The smallest
      effective concentration of perchlorate capable of significantly reducing
      colloidal T(4) ring intensity was 8 microg perchlorate/l. The intensity of the
      immunoreactive colloidal T(4) ring is a more sensitive biomarker of perchlorate
      exposure than changes in hind limb length, forelimb emergence, tail resorption,
      thyrocyte hypertrophy, or colloid depletion. We conclude that the colloidal T(4)
      ring can be used as a sensitive biomarker of perchlorate-induced thyroid
      disruption in amphibians.

PMID- 16807284
TI  - The steroid hormone biosynthesis pathway as a target for endocrine-disrupting
      chemicals.
AB  - Various chemicals found in the human and wildlife environments have the potential
      to disrupt endocrine functions in exposed organisms. Increasingly, the enzymes
      involved in the steroid biosynthesis pathway are being recognized as important
      targets for the actions of various endocrine-disrupting chemicals. Interferences
      with steroid biosynthesis may result in impaired reproduction, alterations in
      (sexual) differentiation, growth, and development and the development of certain
      cancers. Steroid hormone synthesis is controlled by the activity of several
      highly substrate-selective cytochrome P450 enzymes and a number of steroid
      dehydrogenases and reductases. Particularly aromatase (CYP19), the enzyme that
      converts androgens to estrogens, has been the subject of studies into the
      mechanisms by which chemicals interfere with sex steroid hormone homeostasis and
      function, often related to (de)feminization and (de)masculinazation processes.
      Studies in vivo and in vitro have focussed on ovarian and testicular function,
      with less attention given to other steroidogenic organs, such as the adrenal
      cortex. This review aims to provide a comprehensive overview of the state of
      knowledge regarding the mechanisms by which chemicals interfere with the function
      of steroidogenic enzymes in various tissues and organisms. The endocrine
      toxicities and mechanisms of action related to steroidogenesis of a number of
      classes of drugs and environmental contaminants are discussed. In addition,
      several potential in vitro bioassays are reviewed for their usefulness as
      screening tools for the detection of chemicals that can interfere with
      steroidogenesis. Analysis of the currently scattered state of knowledge indicates
      that still relatively little is known about the underlying mechanisms of
      interference of chemicals with steroidogenesis and their potential toxicity in
      steroidogenic tissues, neither in humans nor in wildlife. Considerably more
      detailed and systematic research in this area of (endocrine) toxicology is
      required for a better understanding of risks to humans and wildlife.

PMID- 16807285
TI  - Tissue distribution and ontogeny of sulfotransferase enzymes in mice.
AB  - Sulfotransferases (Sults) are phase-II conjugation enzymes that catalyze the
      transfer of a sulfonate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS)
      to target endo and xenobiotics. PAPS is formed from inorganic sulfate by the
      action of the enzyme PAPS synthase (PAPSs). In the present study, the tissue
      distribution and developmental changes in the mRNA expression of 11 Sult isozymes
      and 2 PAPSs isoforms in mice were quantified. Sult1a1, 1b1, 1c1, 1c2, 1d1, 1e1,
      2a1/2, 2b1, 3a1, 4a1, 5a1, PAPSs1, and PAPSs2 mRNA expression was quantified in
      14 tissues from male and female mice using the branched DNA signal amplification
      assay. Sult2a1/2 and 3a1 expression were highest in liver; Sult1b1, 2b1, and
      PAPSs2 in small intestine; Sult1a1 in large intestine; Sult1c2 in stomach;
      Sult1d1 in kidney; Sult1e1 in placenta; and Sult4a1 in brain. Sult1c1, 5a1, and
      PAPSs1 were ubiquitously expressed in most tissues. These enzymes demonstrated
      three different ontogenic expression patterns in liver. Sult1a1, 1c2, 1d1, 2a1/2,
      and PAPSs2 hepatic expression gradually increased from birth until about 3 weeks
      of age and then declined somewhat thereafter, Sult1c1 expression was highest
      before birth and declined after that, and Sult3a1 mRNA expression was very low in
      fetal livers and remained low until 30 days of age, when expression in females
      dramatically increased, whereas it never increased in males. The organ-specific
      distribution of Sults as well as the different expression of the Sults in young
      animals may affect the pharmacokinetic behavior and organ-specific toxicity of
      xenobiotics.

PMID- 16807286
TI  - Methoxychlor inhibits growth and induces atresia of antral follicles through an
      oxidative stress pathway.
AB  - The mammalian ovary contains antral follicles, which are responsible for the
      synthesis and secretion of hormones that regulate estrous cyclicity and
      fertility. The organochlorine pesticide methoxychlor (MXC) causes atresia
      (follicle death via apoptosis) of antral follicles, but little is known about the
      mechanisms by which MXC does so. Oxidative stress is known to cause apoptosis in
      nonreproductive and reproductive tissues. Thus, we tested the hypothesis that MXC
      inhibits growth and induces atresia of antral follicles through an oxidative
      stress pathway. To test this hypothesis, antral follicles isolated from 39-day
      old CD-1 mice were cultured with vehicle control (dimethylsulfoxide [DMSO]), MXC
      (1-100 microg/ml), or MXC + the antioxidant N-acetyl cysteine (NAC) (0.1-10 mM).
      During culture, growth was monitored daily. At the end of culture, follicles were
      processed for quantitative real-time polymerase chain reaction of Cu/Zn
      superoxide dismutase (SOD1), glutathione peroxidase (GPX), and catalase (CAT)
      mRNA expression or for histological evaluation of atresia. The results indicate
      that exposure to MXC (1-100 microg/ml) inhibited growth of follicles compared to
      DMSO controls and that NAC (1-10 mM) blocked the ability of MXC to inhibit
      growth. MXC induced follicular atresia, whereas NAC (1-10 mM) blocked the ability
      of MXC to induce atresia. In addition, MXC reduced the expression of SOD1, GPX,
      and CAT, whereas NAC reduced the effects of MXC on their expression.
      Collectively, these data indicate MXC causes slow growth and increased atresia by
      inducing oxidative stress.

PMID- 16807287
TI  - Prevalence of serum antibodies to human papilloma virus in patients with genital
      ulcer disease in an urban population of Tanzania.
AB  - BACKGROUND: The epidemiology of human papillomavirus (HPV) in Tanzania is largely
      unknown both in risk groups and in the general population. OBJECTIVE: To
      determine the cumulative seroprevalence of selected HPV types in order to
      evaluate exposure to HPV in urban Tanzania. METHOD: In a cross-sectional study,
      sera of 200 patients of both sexes with genital ulcer disease (GUD) and sera of
      60 male blood donors and 60 pregnant women were tested for antibodies to the
      oncogenic HPV types 16, 18, 31, 33, 35, 51 and 52 using an ELISA based on virus
      like particles (VLP). RESULTS: The overall seroprevalence of HPV types for all
      patients with GUD was 83% and 77% for women and men, respectively. For pregnant
      women and male blood donors, the corresponding percentages were 55% and 15%,
      respectively. The most common HPV types were 16, 18 and 52. Infection with
      multiple types was more than 10 and 5 times more frequent than infection with a
      single type 16 in patients with GUD and in pregnant women, respectively. The
      seroprevalence to HPV types 16, 18, 51 and 52 was considerably higher in HIV
      positive patients with GUD than in HIV-negative patients. CONCLUSIONS: Infections
      with the oncogenic HPV types 16, 18 and 52 are common among patients with GUD and
      pregnant women in urban Tanzania, emphasising the need for control, treatment and
      implementation of appropriate HPV vaccine programmes.

PMID- 16807288
TI  - Sex work in Tallinn, Estonia: the sociospatial penetration of sex work into
      society.
AB  - BACKGROUND: It is important to describe and understand the underlying patterns
      and dynamics that govern sex work in societies undergoing rapid political and
      social changes, its heterogeneity across populations, and its evolution through
      time in order to inform future research, sound policy formation, and programme
      delivery. OBJECTIVES: To describe the socioeconomic and cultural determinants,
      organisational structure, distinct categories, and spatial patterning of sex work
      in Tallinn, Estonia, and identify recent temporal changes in sex work patterns.
      METHODS: In-depth interviews with key informants; naturalistic observations of
      sex work and drug use venues, geo-mapping of sex work sites, review of media,
      public policy, and commissioned reports, and analyses of existing data. RESULTS:
      Sex work takes place in a hierarchy of locations in Tallinn ranging from elite
      brothels and "love flats" to truck stops. These sites vary in terms of their
      public health importance and social organisation. There are full time, part time,
      and intermittent male and female sex workers. Among others, the taxi driver,
      madam and the bartender are central roles in the organisation of sex work in
      Tallinn. Cell phone and internet technology enable sex work to be highly
      dispersed and spatially mobile. CONCLUSION: Future research and programmatic
      service delivery or outreach efforts should respond to the changing profile of
      sex work in Tallinn and its implications for STD/HIV epidemiology.

PMID- 16807289
TI  - Management of a syphilis outbreak in street sex workers in east London.
AB  - OBJECTIVE: To describe the control and management of a syphilis outbreak in
      female street sex workers (SSWs) in east London. METHODS: Following the
      identification of several cases of infectious syphilis in SSWs in east London, a
      targeted service for screening and treatment of syphilis and other sexually
      transmitted infections was developed. A multidisciplinary team (MDT) joined an
      existing outreach service to facilitate this. Once it became apparent that this
      was not an isolated case, an outbreak control team (OCT) was established.
      RESULTS: Between April and December 2004 a total of 14 (58%) women with 15 cases
      of infectious syphilis were identified in 24 SSWs: 14/15 (93%) received
      treatment. Epidemiological treatment for syphilis was also given to the rest of
      SSWs at the initial visit. Several coexistent STIs were identified in this
      cohort. As part of the enhanced outbreak surveillance in north east London, 21
      cases of infectious syphilis were reported in SSWs between April 2004 and
      December 2005. CONCLUSION: Outbreak management in this population was
      challenging: an MDT approach was crucial in identifying and treating syphilis to
      prevent onward transmission. There was a high prevalence of syphilis and other
      STIs in this cohort, and we treated the majority of cases. The formation of an
      OCT enabled us to monitor the outbreak and implement control measures more
      effectively. The novel intervention we describe has proved valuable in helping to
      control this syphilis outbreak.

PMID- 16807291
TI  - GEP100/BRAG2: activator of ADP-ribosylation factor 6 for regulation of cell
      adhesion and actin cytoskeleton via E-cadherin and alpha-catenin.
AB  - GEP(100) (p100) was identified as an ADP-ribosylation factor (ARF) guanine
      nucleotide-exchange protein (GEP) that partially colocalized with ARF6 in the
      cell periphery. p100 preferentially accelerated guanosine 5[gamma
      thio]triphosphate (GTPgammaS) binding by ARF6, which participates in protein
      trafficking near the plasma membrane, including receptor recycling, cell
      adhesion, and cell migration. Here we report that yeast two-hybrid screening of a
      human fetal brain cDNA library using p100 as bait revealed specific interaction
      with alpha-catenin, which is known as a regulator of adherens junctions and actin
      cytoskeleton remodeling. Interaction of p100 with alpha-catenin was confirmed by
      coimmunoprecipitation of the endogenous proteins from human HepG2 or CaSki cells,
      although colocalization was difficult to demonstrate microscopically. alpha
      Catenin enhanced GTPgammaS binding by ARF6 in vitro in the presence of p100.
      Depletion of p100 by small interfering RNA (siRNA) treatment in HepG2 cells
      resulted in E-cadherin content 3-fold that in control cells and blocked
      hepatocyte growth factor-induced redistribution of E-cadherin, consistent with a
      known role of ARF6 in this process. F-actin was markedly decreased in normal rat
      kidney (NRK) cells overexpressing wild-type p100, but not its GEP-inactive
      mutants, also consistent with the conclusion that p100 has an important role in
      the activation of ARF6 for its functions in both E-cadherin recycling and actin
      remodeling.

PMID- 16807292
TI  - Implications of structures of synaptic tetramers of gamma delta resolvase for the
      mechanism of recombination.
AB  - The structures of two mutants of the site-specific recombinase, gammadelta
      resolvase, that form activated tetramers have been determined. One, at 3.5-A
      resolution, forms a synaptic intermediate of resolvase that is covalently linked
      to two cleaved DNAs, whereas the other is of an unliganded structure determined
      at 2.1-A resolution. Comparisons of the four known tetrameric resolvase
      structures show that the subunits interact through the formation of a common core
      of four helices. The N-terminal halves of these helices superimpose well on each
      other, whereas the orientations of their C termini are more variable. The
      catalytic domains of resolvase in the unliganded structure are arranged
      asymmetrically, demonstrating that their positions can move substantially while
      preserving the four-helix core that forms the tetramer. These results suggest
      that the precleavage synaptic tetramer of gammadelta resolvase, whose structure
      is not known, may be formed by a similar four-helix core, but differ in the
      relative orientations of its catalytic and DNA-binding domains.

PMID- 16807293
TI  - Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis
      through sustained c-Jun N-terminal kinase 1 activation.
AB  - A major link between inflammation and cancer is provided by NF-kappaB
      transcription factors. Ikkbeta(Deltahep) mice, which specifically lack IkappaB
      kinase beta (IKKbeta), an activator of NF-kappaB, in hepatocytes, are unable to
      activate NF-kappaB in response to proinflammatory stimuli, such as TNF-alpha.
      Surprisingly, Ikkbeta(Deltahep) mice are hypersusceptible to diethylnitrosamine
      (DEN)-induced hepatocarcinogenesis. Because defective NF-kappaB activation
      promotes sustained c-Jun N-terminal kinase (JNK) activation in cells exposed to
      TNF-alpha, whose expression is induced by DEN, and JNK activity is required for
      normal hepatocyte proliferation, we examined whether increased susceptibility to
      DEN-induced hepatocarcinogenesis in Ikkbeta(Deltahep) mice requires JNK
      activation. Hepatocytes express both JNK1 and JNK2, but previous studies indicate
      that JNK1 is more important for hepatocyte proliferation. We therefore
      investigated this hypothesis using mice homozygous for a JNK1 deficiency either
      in wild-type or Ikkbeta(Deltahep) backgrounds. In both cases, mice lacking JNK1
      were much less susceptible to DEN-induced hepatocarcinogenesis. This impaired
      tumorigenesis correlated with decreased expression of cyclin D and vascular
      endothelial growth factor, diminished cell proliferation, and reduced tumor
      neovascularization. Whereas hepatocyte-specific deletion of IKKbeta augmented DEN
      induced hepatocyte death and cytokine-driven compensatory proliferation,
      disruption of JNK1 abrogated this response. In addition to underscoring the
      importance of JNK1-mediated hepatocyte death and compensatory proliferation,
      these results strongly suggest that the control of tissue renewal through the IKK
      and JNK pathways plays a key role in liver carcinogenesis.

PMID- 16807294
TI  - The dominant role of CD8+ dendritic cells in cross-presentation is not dictated
      by antigen capture.
AB  - Mouse spleens contain three populations of conventional (CD11c(high)) dendritic
      cells (DCs) that play distinct functions. The CD8(+) DC are unique in that they
      can present exogenous antigens on their MHC class I molecules, a process known as
      cross-presentation. It is unclear whether this special ability is because only
      the CD8(+) DC can capture the antigens used in cross-presentation assays, or
      because this is the only DC population that possesses specialized machinery for
      cross-presentation. To solve this important question we examined the splenic DC
      subsets for their ability to both present via MHC class II molecules and cross
      present via MHC class I using four different forms of the model antigen ovalbumin
      (OVA). These forms include a cell-associated form, a soluble form, OVA expressed
      in bacteria, or OVA bound to latex beads. With the exception of bacterial
      antigen, which was poorly cross-presented by all DC, all antigenic forms were
      cross-presented much more efficiently by the CD8(+) DC. This pattern could not be
      attributed simply to a difference in antigen capture because all DC subsets
      presented the antigen via MHC class II. Indeed, direct assessments of endocytosis
      showed that CD8(+) and CD8(-) DC captured comparable amounts of soluble and bead
      associated antigen, yet only the CD8(+) DC cross-presented these antigenic forms.
      Our results indicate that cross-presentation requires specialized machinery that
      is expressed by CD8(+) DC but largely absent from CD8(-) DC. This conclusion has
      important implications for the design of vaccination strategies based on antigen
      targeting to DC.

PMID- 16807295
TI  - Structure-function-folding relationship in a WW domain.
AB  - Protein folding barriers result from a combination of factors including
      unavoidable energetic frustration from nonnative interactions, natural variation
      and selection of the amino acid sequence for function, and/or selection pressure
      against aggregation. The rate-limiting step for human Pin1 WW domain folding is
      the formation of the loop 1 substructure. The native conformation of this six
      residue loop positions side chains that are important for mediating protein
      protein interactions through the binding of Pro-rich sequences. Replacement of
      the wild-type loop 1 primary structure by shorter sequences with a high
      propensity to fold into a type-I' beta-turn conformation or the statistically
      preferred type-I G1 bulge conformation accelerates WW domain folding by almost an
      order of magnitude and increases thermodynamic stability. However, loop
      engineering to optimize folding energetics has a significant downside: it
      effectively eliminates WW domain function according to ligand-binding studies.
      The energetic contribution of loop 1 to ligand binding appears to have evolved at
      the expense of fast folding and additional protein stability. Thus, the two-state
      barrier exhibited by the wild-type human Pin1 WW domain principally results from
      functional requirements, rather than from physical constraints inherent to even
      the most efficient loop formation process.

PMID- 16807296
TI  - Prey evolution on the time scale of predator-prey dynamics revealed by allele
      specific quantitative PCR.
AB  - Using rotifer-algal microcosms, we tracked rapid evolution resulting from
      temporally changing natural selection in ecological predator-prey dynamics. We
      previously demonstrated that predator-prey oscillations in rotifer-algal
      laboratory microcosms are qualitatively altered by the presence of genetic
      variation within the prey. In that study, changes in algal gene frequencies were
      inferred from their effects on population dynamics but not observed directly.
      Here, we document rapid prey evolution in this system by directly observing
      changes in Chlorella vulgaris genotype frequencies as the abundances of these
      algae and their consumer, Brachionus calyciflorus, change through time. We
      isolated a group of algal clones that we could distinguish by using
      microsatellite-DNA markers, and developed an allele-specific quantitative PCR
      technique (AsQ-PCR) to quantify the frequencies of pairs of clones in mixed
      culture. We showed that two of these genotypes exhibited a fitness tradeoff in
      which one was more resistant to predation (more digestion-resistant), and the
      other had faster population growth under limiting nitrogen concentrations. A
      fully specified mathematical model for the rotifer-algal population and
      evolutionary dynamics predicted that these two clones would undergo a single
      oscillation in clonal frequencies followed by asymptotic fixation of the more
      resistant clone, rather than the recurrent oscillations previously observed with
      other algal clones. We used AsQ-PCR to confirm this prediction: the superior
      competitor dominated initially, but as rotifer densities increased, the more
      predator-resistant clone predominated.

PMID- 16807297
TI  - Biological versus nonbiological older brothers and men's sexual orientation.
AB  - The most consistent biodemographic correlate of sexual orientation in men is the
      number of older brothers (fraternal birth order). The mechanism underlying this
      effect remains unknown. In this article, I provide a direct test pitting prenatal
      against postnatal (e.g., social/rearing) mechanisms. Four samples of homosexual
      and heterosexual men (total n = 944), including one sample of men raised in
      nonbiological and blended families (e.g., raised with half- or step-siblings or
      as adoptees) were studied. Only biological older brothers, and not any other
      sibling characteristic, including nonbiological older brothers, predicted men's
      sexual orientation, regardless of the amount of time reared with these siblings.
      These results strongly suggest a prenatal origin to the fraternal birth-order
      effect.

PMID- 16807298
TI  - Ouabain induces cell proliferation through calcium-dependent phosphorylation of
      Akt (protein kinase B) in opossum kidney proximal tubule cells.
AB  - Cardiotonic glycosides, like ouabain, inhibit Na(+)-K(+)-ATPase. Recent evidence
      suggests that low molar concentrations of ouabain alter cell growth. Studies were
      conducted to examine the effect of ouabain on Akt phosphorylation and rate of
      cell proliferation in opossum kidney (OK) proximal tubule cells. Cells exposed to
      10 nM ouabain displayed increased Akt Ser(473) phosphorylation, as evidenced by
      an increase in phospho-Akt Ser(473) band density. Ouabain-stimulated Akt Ser(473)
      phosphorylation was inhibited by pretreatment with phosphatidylinositol 3-kinase
      (PI3K) inhibitors (LY294002 and wortmannin), a PLC inhibitor (edelfosine), and an
      Akt inhibitor. Moreover, ouabain-mediated Akt Ser(473) phosphorylation was
      suppressed by reduction of extracellular calcium (EGTA) or when intracellular
      calcium was buffered by BAPTA-AM. An inhibitor of calcium store release (TMB-8)
      and an inhibitor of calcium entry via store-operated calcium channels (SKF96365)
      also suppressed ouabain-mediated Akt Ser(473) phosphorylation. In fura-2 AM
      loaded cells, 10 nM ouabain increased capacitative calcium entry (CCE). Ouabain
      at 10 nM did not significantly alter baseline cytoplasmic calcium concentration
      in control cells. However, treatment with 10 nM ouabain caused a significantly
      higher ATP-mediated calcium store release. After 24 h, 10 nM ouabain increased
      the rate of cell proliferation. The Akt inhibitor, BAPTA-AM, SKF96365, and
      cyclopiazonic acid suppressed the increase in the rate of cell proliferation
      caused by 10 nM ouabain. Ouabain at 10 nM caused a detectable increase in (86)Rb
      uptake but did not significantly alter Na(+)-K(+)-ATPase (ouabain-sensitive
      pNPPase) activity in crude membranes or cell sodium content. Taken together, the
      results point to a role for CCE and Akt phosphorylation, in response to low
      concentrations of ouabain, that increase the rate of cell proliferation without
      inhibiting Na(+)-K(+)-ATPase-mediated ion transport.

PMID- 16807299
TI  - Lidocaine depresses splenocyte immune functions following trauma-hemorrhage in
      mice.
AB  - Traumatic and/or surgical injury as well as hemorrhage induces profound
      suppression of cellular immunity. Although local anesthetics have been shown to
      impair immune responses, it remains unclear whether lidocaine affects lymphocyte
      functions following trauma-hemorrhage (T-H). We hypothesized that lidocaine will
      potentiate the suppression of lymphocyte functions after T-H. To test this, we
      randomly assigned male C3H/HeN (6-8 wk) mice to sham operation or T-H. T-H was
      induced by midline laparotomy and approximately 90 min of hemorrhagic shock
      (blood pressure 35 mmHg), followed by fluid resuscitation (4x shed blood volume
      in the form of Ringer lactate). Two hours later, the mice were killed and
      splenocytes and bone marrow cells were isolated. The effects of lidocaine on
      concanavalin A-stimulated splenocyte proliferation and cytokine production in
      both sham-operated and T-H mice were assessed. The effects of lidocaine on LPS
      stimulated bone marrow cell proliferation and cytokine production were also
      assessed. The results indicate that T-H suppresses cell proliferation, Th1
      cytokine production, and MAPK activation in splenocytes. In contrast, cell
      proliferation, cytokine production, and MAPK activation in bone marrow cells were
      significantly higher 2 h after T-H compared with shams. Lidocaine depressed
      immune responses in splenocytes; however, it had no effect in bone marrow cells
      in either sham or T-H mice. The enhanced immunosuppressive effects of lidocaine
      could contribute to the host's enhanced susceptibility to infection following T
      H.

PMID- 16807300
TI  - Mitoenergetic failure in Alzheimer disease.
AB  - Brain cells are highly energy dependent for maintaining ion homeostasis during
      high metabolic activity. During active periods, full mitochondrial function is
      essential to generate ATP from electrons that originate with the oxidation of
      NADH. Decreasing brain metabolism is a significant cause of cognitive
      abnormalities of Alzheimer disease (AD), but it remains uncertain whether this is
      the cause of further pathology or whether synaptic loss results in a lower energy
      demand. Synapses are the first to show pathological symptoms in AD before the
      onset of clinical symptoms. Because synaptic function has high energy demands,
      interruption in mitochondrial energy supply could be the major factor in synaptic
      failure in AD. A newly discovered age-related decline in neuronal NADH and redox
      ratio may jeopardize this function. Mitochondrial dehydrogenases and several
      mutations affecting energy transfer are frequently altered in aging and AD. Thus,
      with the accumulation of genetic defects in mitochondria at the level of energy
      transfer, the issue of neuronal susceptibility to damage as a function of age and
      age-related disease becomes important. In an aging rat neuron model, mitochondria
      are both chronically depolarized and produce more reactive oxygen species with
      age. These concepts suggest that multiple treatment targets may be needed to
      reverse this multifactorial disease. This review summarizes new insights based on
      the interaction of mitoenergetic failure, glutamate excitotoxicity, and amyloid
      toxicity in the exacerbation of AD.

PMID- 16807301
TI  - Physiological diversity of mitochondrial oxidative phosphorylation.
AB  - To investigate the physiological diversity in the regulation and control of
      mitochondrial oxidative phosphorylation, we determined the composition and
      functional features of the respiratory chain in muscle, heart, liver, kidney, and
      brain. First, we observed important variations in mitochondrial content and
      infrastructure via electron micrographs of the different tissue sections.
      Analyses of respiratory chain enzyme content by Western blot also showed large
      differences between tissues, in good correlation with the expression level of
      mitochondrial transcription factor A and the activity of citrate synthase. On the
      isolated mitochondria, we observed a conserved molar ratio between the
      respiratory chain complexes and a variable stoichiometry for coenzyme Q and
      cytochrome c, with typical values of [1-1.5]:[30-135]:[3]:[9-35]:[6.5-7.5] for
      complex II:coenzyme Q:complex III:cytochrome c:complex IV in the different
      tissues. The functional analysis revealed important differences in maximal
      velocities of respiratory chain complexes, with higher values in heart. However,
      calculation of the catalytic constants showed that brain contained the more
      active enzyme complexes. Hence, our study demonstrates that, in tissues,
      oxidative phosphorylation capacity is highly variable and diverse, as determined
      by different combinations of 1) the mitochondrial content, 2) the amount of
      respiratory chain complexes, and 3) their intrinsic activity. In all tissues,
      there was a large excess of enzyme capacity and intermediate substrate
      concentration, compared with what is required for state 3 respiration. To
      conclude, we submitted our data to a principal component analysis that revealed
      three groups of tissues: muscle and heart, brain, and liver and kidney.

PMID- 16807302
TI  - Disruption of alpha-actinin-integrin interactions at focal adhesions renders
      osteoblasts susceptible to apoptosis.
AB  - Maintenance of bone structural integrity depends in part on the rate of apoptosis
      of bone-forming osteoblasts. Because substrate adhesion is an important regulator
      of apoptosis, we have investigated the role of focal adhesions in regulating bone
      cell apoptosis. To test this, we expressed a truncated form of alpha-actinin (ROD
      GFP) that competitively displaces endogenous alpha-actinin from focal adhesions,
      thus disrupting focal adhesions. Immunofluorescence and morphometric analysis of
      vinculin and tyrosine phosphorylation revealed that ROD-GFP expression
      dramatically disrupted focal adhesion organization and reduced tyrosine
      phosphorylation at focal adhesions. In addition, Bcl-2 protein levels were
      reduced in ROD-GFP-expressing cells, but caspase 3 cleavage, poly(ADP-ribose)
      polymerase cleavage, histone H2A.X phosphorylation, and cytotoxicity were not
      increased due to ROD-GFP expression alone. Increases in both ERK and Akt
      phosphorylation were also observed in ROD-GFP-expressing cells, although
      inhibition of either ERK or Akt individually or together failed to induce
      apoptosis. However, we did find that ROD-GFP expression sensitized, whereas alpha
      actinin-GFP expression protected, cells from TNF-alpha-induced apoptosis. Further
      investigation revealed that activation of TNF-alpha-induced survival signals,
      specifically Akt phosphorylation and NF-kappaB activation, was inhibited in ROD
      GFP-expressing cells. The reduced expression of antiapoptotic Bcl-2 and inhibited
      survival signaling rendered ROD-GFP-expressing cells more susceptible to TNF
      alpha-induced apoptosis. Thus we conclude that alpha-actinin plays a role in
      regulating cell survival through stabilization of focal adhesions and regulation
      of TNF-alpha-induced survival signaling.

PMID- 16807303
TI  - ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice.
AB  - Obesity has been linked to cardiovascular disease, hypertension, diabetes and the
      metabolic syndrome, with elevated markers of systemic inflammation. Intercellular
      adhesion molecule-1 (ICAM-1) is a transmembrane adhesion molecule involved in
      leukocyte migration to sites of inflammation. In human obesity, elevated
      expression of the soluble form of ICAM-1 (sICAM-1) is positively correlated with
      abdominal fat deposition. Increases in adiposity have also been correlated with
      macrophage infiltration into adipose tissue. Here we investigate adipose tissue
      production and transcriptional regulation of ICAM-1 in a mouse model of dietary
      obesity. After feeding mice a high-fat diet, ICAM-1 expression in serum and
      adipose tissue was analyzed by ELISA, Northern blotting, real-time quantitative
      PCR, and flow cytometry. After 6 mo on the high-fat diet, sICAM-1 levels
      significantly correlated with body weight and abdominal fat mass. ICAM-1 mRNA was
      expressed in adipose tissue of mice, with significantly higher levels in males
      than females. After only 3 wk, there were adipose tissue-specific increases in
      mRNAs for ICAM-1, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in male
      mice. Analysis of the stromal-vascular fraction of male adipose tissue revealed
      CD11b-negative cells with increased surface ICAM-1 and CD34. We also found two
      populations of F4/80+, CD11b+, ICAM-1+ cells, one of which also expressed CD14
      and CD11c and was increased in response to a high-fat diet. These results
      indicate that within 3 wk on a high-fat diet, male mice exhibited significant
      increases in pro-inflammatory factors and immune cell infiltration in adipose
      tissue that may represent links between obesity and its associated inflammatory
      complications.

PMID- 16807304
TI  - Mobilisation of mesenchymal cells into blood in response to skeletal muscle
      injury.
AB  - Mesenchymal cells recruited to damaged tissues must circulate through the
      bloodstream. The absolute numbers of circulating mesenchymal stem cells (cMSCs)
      in two different models of acute and chronic skeletal muscle injury were
      determined. cMSCs were present in significantly higher numbers in both models
      than in healthy controls. These results support the hypothesis that MSCs are
      mobilised into the bloodstream after skeletal muscle tissue damage. These two
      models (acute and chronic) would be of value in the search for molecular
      mediators of mobilisation of MSCs into the circulation.

PMID- 16807305
TI  - Ultrasound guided electrocoagulation in patients with chronic non-insertional
      Achilles tendinopathy: a pilot study.
AB  - BACKGROUND: High resolution colour Doppler ultrasound shows intratendinous
      Doppler activity in patients with chronic Achilles tendinopathy. Treatment of
      this neovascularisation with sclerosing therapy seems to relieve the pain.
      However, the procedure often has to be repeated. OBJECTIVE: To investigate the
      effect of electrocoagulation of the neovessels on tendon pain and tendon
      vascularity in patients with chronic Achilles tendinopathy. METHODS: Colour
      Doppler ultrasound guided electrocoagulation was used on vessels in the ventral
      portion of the Achilles tendon in 11 patients (seven men, four women, mean age 41
      years) with painful chronic mid-portion Achilles tendinosis. A unipolar
      coagulation device was used. RESULTS: One patient dropped out after two months
      (dissatisfied with the results). The remaining 10 patients (91%) were satisfied.
      These 10 patients were still satisfied at six months of follow up and had
      returned to their previous level of activity. All 10 patients were "cured" after
      one treatment. The patient who dropped out received two treatments because of
      lack of progress. There was significantly reduced pain (Likert pain scale, 0-10)
      during activity, from a median of 7 (range 4 to 10) at baseline to 0 (0 to 8) at
      six months' follow up (p<0.005); and at rest, from 1.5 (1 to 5) to 0 (0 to 8) (p
      = 0.005). In all patients, vascularisation was unchanged at the six months follow
      up, with no significant change in semiquantitative or quantitative colour
      scoring. CONCLUSIONS: Coagulation in the area with vessels entering the tendon
      appears to be effective treatment for painful chronic mid-tendinous Achilles
      tendinopathy. No effect on the intratendinous Doppler activity could be detected,
      suggesting that the effect is independent of changes in blood flow. Localisation
      of hyperaemia appears to be the key to the pathology and for targeting the
      treatment. One explanation could be that the effect is obtained by destruction of
      nerves accompanying the vessels.

PMID- 16807306
TI  - A prospective cohort study of injury in amateur and professional boxing.
AB  - BACKGROUND: There is concern over the potential for a high incidence of injury in
      boxing. This is despite a lack of prospective data evaluating the risk for modern
      day participants. Updated, reliable data with a focus on potential exposure to
      injury for both amateur and, especially, professional boxers is required. AIM: To
      determine the epidemiology of injury and exposure of amateur and professional
      boxers in Victoria, Australia. METHODS: A prospective cohort study with one year
      follow up was carried out over 2004-2005. Thirty three amateur and 14 active
      professional boxers registered with either Boxing Victoria Inc (amateurs) or the
      Professional Boxing and Combat Sports Board of Victoria (professionals)
      volunteered. Exposure at training and competition was measured, and any injuries
      sustained during this participation were recorded. RESULTS: Twenty one injuries
      were sustained by the cohort during the follow up period. Most were to the head
      region (71%; 95% confidence interval -3.7 to 89.4), with concussion being the
      most common (33%). An overall injury rate of 2.0 injuries per 1000 hours of
      boxing was calculated. CONCLUSION: The high exposure experienced by the boxers
      (as a result of considerable training time) indicated that boxing has acute
      injury rates comparable to, and often lower than, those found in other contact
      and non-contact sports. Further, acute injuries during training appear to be less
      common and severe than those sustained in bouts.

PMID- 16807307
TI  - Physeal injuries in children's and youth sports: reasons for concern?
AB  - A systematic review of the literature on the frequency and characteristics of
      sports related growth plate injuries affecting children and youth in organised
      sport was carried out. Both acute and chronic physeal injuries related to
      participation in sports have been reported to occur, although injury incidence
      data are somewhat limited. Of particular concern is the growing number of stress
      related physeal injuries, including those affecting the lower extremities.
      Although most physeal injuries appeared to resolve with treatment and rest, there
      is also evidence of growth disturbance and deformity. Possible injury risk
      factors and countermeasures are discussed, and suggestions for directing future
      research provided.

PMID- 16807309
TI  - Advance care planning and hospital in the nursing home.
AB  - BACKGROUND: the number of nursing home residents (NHRs) in hospital is increasing
      although hospital admission may be deleterious to their health. OBJECTIVE: to
      evaluate a system of educating residents, their families, staff and general
      practitioners about outcomes of dementia, advance care planning (ACP) and
      hospital in the home. METHODS: we employed one clinical nurse consultant, who
      utilised the 'Let Me Decide' Advance Care Directive. The intervention area
      consisted of two hospitals and the 21 nursing homes (NHs) around them compared
      with another, geographically separate, hospital and the 13 homes around it. We
      conducted a controlled evaluation monitoring emergency admissions to hospital.
      RESULTS: emergency calls to the ambulance service from intervention NHs decreased
      (intervention versus control; -1 versus +21%; P = 0.0019). The risk of a resident
      being in an intervention hospital bed for a day compared with in a control
      hospital bed, per NH bed, fell by a quarter from being initially similar
      [Relative Risk (RR) = 1.01; 95% confidence interval (CI) 0.98-1.04; P = 0.442] to
      being lower (RR = 0.74; 95% CI 0.72-0.77; P<0.0001). There was no significant
      change in mortality in the intervention homes, but in the control homes mortality
      rose in the third year to be 11.2 per 100 beds higher than in the intervention
      area (P<0.05). CONCLUSION: ACP and hospital in the home can result in decreased
      hospital admission and mortality of NHRs.

PMID- 16807310
TI  - Use of antipsychotics among nonagenarian residents in long-term institutional
      care in Finland.
AB  - BACKGROUND: There is a paucity of information about the use of antipsychotic
      medication in long-term care, especially among the oldest-old residents.
      OBJECTIVE: To analyse the factors associated with the use of antipsychotic
      medication among nonagenarian residents in long-term institutional care. DESIGN:
      A retrospective study was designed from cross-sectional data, gathered in the
      period 1 January 2003 to 30 June 2003, in Finland. Data were extracted from the
      Resident Assessment Instrument database, based on Minimum Data Set 2.0
      assessments. SETTING: Data were provided by 23 hospital-based institutions and 43
      residential homes. SUBJECTS: Residents aged >or=90 years were included,
      consisting of 1,334 resident assessments. RESULTS: Almost a third of the
      residents received one or more antipsychotic medication. In the logistic
      regression analysis, factors associated with the use of antipsychotics among
      nonagenarian residents were as follows: socially inappropriate or disruptive
      behavioural symptoms [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.36
      2.54], concomitant anxiolytic medication (OR 1.83, 95% CI 1.39-2.42), recurring
      anxious complaints (OR 1.61, 95% CI 1.17-2.22), recurring physical movements (OR
      1.43, 95% CI 1.08-1.91) and unsettled relationships (OR 1.35, 95% CI 1.15-1.57).
      A good sense of initiative or involvement was significantly less likely to be
      associated with antipsychotics (OR 0.86, 95% CI 0.80-0.94). There were no
      associations between any psychiatric diagnoses or symptoms and the use of
      antipsychotics. CONCLUSIONS: Antipsychotic medication use in nonagenarians in
      long-term institutions was common and seemed in many cases to be associated with
      residents' negative attitudes to others. Querulous residents received
      antipsychotics more commonly than those with good social skills. Clearly defined
      indications may not be fulfilled in many cases, and an evaluation of treatment
      may be lacking. These may indicate that in Finland, there could be a considerable
      gap between antipsychotic medication recommendations and actual clinical
      practice.

PMID- 16807311
TI  - Alzheimer's Quick Test cognitive screening criteria for West African speakers of
      Krio.
AB  - OBJECTIVES: To obtain normative data for Alzheimer's Quick Test (AQT) measures of
      perceptual and cognitive speed from West African speakers of Krio. SUBJECTS:
      Normal adults, who were functionally independent, from Sierra Leone (n = 164)
      aged 25-79 years. METHODS: Perceptual and cognitive speed were measured with AQT
      single- and dual-dimension colour-number (C-N) and colour-animal (C-A) naming
      tasks. Tests were administered individually in the participants' communities.
      RESULTS: Men and women performed similarly (P>0.05), whereas literate speakers
      used significantly less time than preliterate peers (P<0.01). Correlations
      between age and colour naming were low (P<0.01) and speed decreased by <0.1 s per
      year. Dual-dimension naming remained stable across ages. Correlations with years
      of education were low for dual-dimension naming (P<0.01) and speed increased
      approximately 0.4 s per added year. Correlations between age and education and
      AQT naming were non-significant for literate participants. Criterion time cut
      offs (seconds) for screening were developed for preliterate and literate speakers
      of Krio for typical (<+1 SD), slower-than-typical (between +1 and +2 SD) and
      atypical (>+2 SD) performance. CONCLUSION: AQT C-N and C-A naming are time
      efficient (3-5 min each), objective and reliable and can be administered in Krio
      to West African adults in Africa, Europe or North America to screen for cognitive
      impairments and facilitate referral for medical workup.

PMID- 16807312
TI  - NO-1886 upregulates ATP binding cassette transporter A1 and inhibits diet-induced
      atherosclerosis in Chinese Bama minipigs.
AB  - It is widely believed that high density lipoprotein-cholesterol (HDL-C) functions
      to transport cholesterol from peripheral cells to the liver by reverse
      cholesterol transport (RCT), a pathway that may protect against atherosclerosis
      by clearing excess cholesterol from arterial cells. A cellular ATP binding
      cassette transporter called ABCA1 mediates the first step of RCT. NO-1886 has
      been proven to be highly effective at increasing HDL-C and reducing
      atherosclerosis. However, the mechanism of atherosclerosis inhibition for NO-1886
      is not fully understood. In this study, the effects of NO-1886 on ABCA1 were
      investigated in high-fat/high-sucrose/high-cholesterol-fed Chinese Bama minipigs.
      Administration of NO-1886 (0.1 g/kg body weight/day) in the diet for 5 months
      significantly reduced atherosclerosis lesions and significantly increased plasma
      HDL-C and apolipoprotein A-I levels. The mRNA and protein levels of ABCA1 in the
      liver, retroperitoneal adipose tissue, and aorta were increased by NO-1886 as
      well. Multivariate linear regression analysis showed that the levels of LPL in
      plasma and the levels of ABCA1 in aorta were independently associated with the
      atherosclerotic lesion area. In addition, NO-1886 upregulated liver X receptor
      alpha and affected the expression of scavenger receptor class B type I in the
      liver. These results demonstrate that the mechanism of atherosclerosis inhibition
      for NO-1886 is associated with its effect on ABCA1.

PMID- 16807313
TI  - Ultra fast miniaturized real-time PCR: 40 cycles in less than six minutes.
AB  - We have designed, fabricated and tested a real-time PCR chip capable of
      conducting one thermal cycle in 8.5 s. This corresponds to 40 cycles of PCR in 5
      min and 40 s. The PCR system was made of silicon micromachined into the shape of
      a cantilever terminated with a disc. The thin film heater and a temperature
      sensor were placed on the disc perimeter. Due to the system's thermal constant of
      0.27 s, we have achieved a heating rate of 175 degrees C s(-1) and a cooling rate
      of -125 degrees C s(-1). A PCR sample encapsulated with mineral oil was dispensed
      onto a glass cover slip placed on the silicon disc. The PCR cycle time was then
      determined by heat transfer through the glass, which took only 0.5 s. A real-time
      PCR sample with a volume of 100 nl was tested using a FAM probe. As the single
      PCR device occupied an area of only a few square millimeters, devices could be
      combined into a parallel system to increase throughput.

PMID- 16807314
TI  - Methylation enrichment pyrosequencing: combining the specificity of MSP with
      validation by pyrosequencing.
AB  - It has been suggested that detection of aberrant DNA methylation in clinical
      specimens such as sputum or saliva may be a valuable tumour biomarker. Any
      clinically applicable detection technique must combine high sensitivity with high
      specificity. In this study we describe methylation enrichment pyrosequencing
      (MEP), which benefits from the high sensitivity and specificity of methylation
      specific PCR (MSP) but has a second, confirmatory, pyrosequencing step. The
      pyrosequencing reaction is rapid, relatively inexpensive and offers significant
      logistical advantages over previously described validation methods. As proof of
      principle, we illustrate MEP using assays of p16 and cyclin A1 promoters in a
      methylated DNA dilution matrix and also in a clinical setting using paired saliva
      and oral tumour specimens. Our results confirm that mis-priming of MSP, with
      subsequent false positive results, can occur frequently (perhaps 10%) in assays
      combining high numbers of PCR cycles and low concentrations of starting DNA. In
      our clinical example, MEP of saliva-derived DNA was more sensitive than standard
      non-methylation-specific pyrosequencing as illustrated using p16 and cyclin A1
      promoter methylation assays.

PMID- 16807315
TI  - Short, synthetic and selectively 13C-labeled RNA sequences for the NMR structure
      determination of protein-RNA complexes.
AB  - We report an optimized synthesis of all canonical 2'-O-TOM protected
      ribonucleoside phosphoramidites and solid supports containing [13C5]-labeled
      ribose moieties, their sequence-specific introduction into very short RNA
      sequences and their use for the structure determination of two protein-RNA
      complexes. These specifically labeled sequences facilitate RNA resonance
      assignments and are essential to assign a high number of sugar-sugar and
      intermolecular NOEs, which ultimately improve the precision and accuracy of the
      resulting structures. This labeling strategy is particularly useful for the study
      of protein-RNA complexes with single-stranded RNA in solution, which is rapidly
      an increasingly relevant research area in biology.

PMID- 16807316
TI  - Promiscuous mismatch extension by human DNA polymerase lambda.
AB  - DNA polymerase lambda (Pol lambda) is one of several DNA polymerases suggested to
      participate in base excision repair (BER), in repair of broken DNA ends and in
      translesion synthesis. It has been proposed that the nature of the DNA
      intermediates partly determines which polymerase is used for a particular repair
      reaction. To test this hypothesis, here we examine the ability of human Pol
      lambda to extend mismatched primer-termini, either on 'open' template-primer
      substrates, or on its preferred substrate, a 1 nt gapped-DNA molecule having a 5'
      phosphate. Interestingly, Pol lambda extended mismatches with an average
      efficiency of approximately 10(-2) relative to matched base pairs. The match and
      mismatch extension catalytic efficiencies obtained on gapped molecules were
      approximately 260-fold higher than on template-primer molecules. A crystal
      structure of Pol lambda in complex with a single-nucleotide gap containing a
      dG.dGMP mismatch at the primer-terminus (2.40 A) suggests that, at least for
      certain mispairs, Pol lambda is unable to differentiate between matched and
      mismatched termini during the DNA binding step, thus accounting for the
      relatively high efficiency of mismatch extension. This property of Pol lambda
      suggests a potential role as a 'mismatch extender' during non-homologous end
      joining (NHEJ), and possibly during translesion synthesis.

PMID- 16807318
TI  - Genes invoked in the ovarian transition to menopause.
AB  - Menopause and the associated declines in ovarian function are major health issues
      for women. Despite the widespread health impact of this process, the molecular
      mechanisms underlying the aging-specific decline in ovarian function are almost
      completely unknown. To provide the first gene-protein analysis of the ovarian
      transition to menopause, we have established and contrasted RNA gene expression
      profiles and protein localization and content patterns in healthy young and
      perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and
      protein levels that are noted prior to molecular evidence of steroidogenic
      failure. In this model, ovarian reproductive aging displays similarities with
      chronic inflammation and increased sensitivity to environmental cues. Overall,
      our results indicate the presence of mouse climacteric genes that are likely to
      be major players in aging-dependent changes in ovarian function.

PMID- 16807317
TI  - Phosphoproteomics reveals extensive in vivo phosphorylation of Arabidopsis
      proteins involved in RNA metabolism.
AB  - Most regulatory pathways are governed by the reversible phosphorylation of
      proteins. Recent developments in mass spectrometry-based technology allow the
      large-scale analysis of protein phosphorylation. Here, we show the application of
      immobilized metal affinity chromatography to purify phosphopeptides from
      Arabidopsis extracts. Phosphopeptide sequences were identified by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS/MS). A total of 79 unique
      phosphorylation sites were determined in 22 phosphoproteins with a putative role
      in RNA metabolism, including splicing of mRNAs. Among these phosphoproteins, 12
      Ser/Arg-rich (SR) splicing factors were identified. A conserved phosphorylation
      site was found in most of the phosphoproteins, including the SR proteins,
      suggesting that these proteins are targeted by the same or a highly related
      protein kinase. To test this hypothesis, Arabidopsis SR protein-specific kinase 4
      (SRPK4) that was initially identified as an interactor of SR proteins was tested
      for its ability to phosphorylate the SR protein RSp31. In vitro kinase assays
      showed that all in vivo phosphorylation sites of RSp31 were targeted by SRPK4.
      These data suggest that the plant mRNA splicing machinery is a major target of
      phosphorylation and that a considerable number of proteins involved in RNA
      metabolism may be targeted by SRPKs.

PMID- 16807319
TI  - Can autism speak to neuroscience?

PMID- 16807320
TI  - The developmental neurobiology of autism spectrum disorder.

PMID- 16807321
TI  - Heparan sulphation patterns generated by specific heparan sulfotransferase
      enzymes direct distinct aspects of retinal axon guidance at the optic chiasm.
AB  - Retinal ganglion cell (RGC) axons from each eye execute a series of maneuvers as
      they converge on the ventral surface of the brain at the optic chiasm for sorting
      into the optic tracts. Heparan sulfate proteoglycans (HSPGs) are extracellular
      glycoproteins involved in cell-surface interactions. HSPGs exhibit massive
      structural diversity, conferred partly by extensive post-translational
      modification including differential sulfation. Here we examine the roles of HSPG
      sulfation in RGC axon guidance at the chiasm. We identified different axon
      navigation phenotypes in two heparan sulfate sulfotransferase (Hst) mutant
      embryos, Hs2st-/- and Hs6st1-/-, each lacking an enzyme that catalyzes a
      particular HSPG modification. Hs2st-/- embryos display axon disorganization at
      the chiasm. Hs6st1-/- embryos exhibit prolific inter-retinal innervation. We show
      that RGCs express Hs2st and Hs6st1 and that navigation errors made by their axons
      coincide with regions of high Hs2st and/or Hs6st1 expression at the chiasm. Slit
      proteins are expressed at particular locations in the retina and around the
      chiasm and are normally deployed to prevent axons entering inappropriate
      territories. We show that Hs2st and/or Hs6st1 expression coincides with Slit
      expression domains at locations where RGC axons make navigation errors in Hs2st-/
      and Hs6st1-/- mutants and that Hs6st1-/- RGC axons are less sensitive to Slit2
      repulsion than their wild-type counterparts in vitro. We suggest that (1) Hs2st
      and Hs6st1 are each deployed to generate distinct patterns of heparan sulfation
      on RGCs and at the optic chiasm and (2) this differential sulfation directs
      retinal axons through the chiasm, at least in part by modulating the response of
      the navigating growth cone to Slit proteins.

PMID- 16807322
TI  - Layer acquisition by cortical GABAergic interneurons is independent of Reelin
      signaling.
AB  - Functioning of the cerebral cortex requires the coordinated assembly of circuits
      involving glutamatergic projection neurons and GABAergic interneurons. Despite
      their segregated origin in different regions of the telencephalon, projection
      neurons and interneurons born synchronically end up adopting the same cortical
      layer, suggesting that layer acquisition is highly coordinated for both neuronal
      types. The radial migration and laminar arrangement of projection neurons depends
      on Reelin, a secreted glycoprotein expressed near the pial surface during
      embryogenesis. In contrast, the mechanisms controlling layer acquisition by
      cortical interneurons remain essentially unknown. Here, we have used an
      ultrasound-guided transplantation approach to analyze the mechanisms underlying
      the acquisition of laminar locations by cortical interneurons. We found that
      layer acquisition by cortical GABAergic interneurons does not directly depend on
      Reelin signaling. Moreover, interneurons invade their target layers well after
      synchronically generated projection neurons reach their final destination. These
      results suggest a model in which cues provided by projection neurons guide
      cortical interneurons to their appropriate layer, and reveal that, at least for
      some neuronal types, long-range radial migration does not directly require
      Reelin.

PMID- 16807323
TI  - Long-term depression at the mossy fiber-deep cerebellar nucleus synapse.
AB  - Several lines of evidence have indicated that the deep cerebellar nuclei (DCN)
      are a site of memory storage for certain forms of motor learning, most notably
      associative eyelid conditioning. In particular, these experiments, together with
      network models, have implicated the excitatory glutamatergic synapse between
      mossy fibers and DCN neurons in this memory trace. However, to date, evidence for
      persistent use-dependent change in the strength of this synapse has been almost
      entirely absent. Here, we report that high-frequency burst stimulation of mossy
      fibers, either alone or paired with postsynaptic depolarization, gives rise to
      long-term depression (LTD) of the mossy fiber-DCN synapse. This form of LTD is
      not associated with changes in the paired-pulse ratio and is blocked by loading
      with a postsynaptic Ca2+ chelator but not by bath application of an NMDA receptor
      antagonist. Mossy fiber-DCN LTD requires activation of a group I metabotropic
      glutamate receptor (mGluR) and protein translation. Unlike mGluR/translation
      dependent LTD in other brain regions, this form of LTD requires mGluR1 and is
      mGluR5 independent.

PMID- 16807324
TI  - Temperature-dependent shift of balance among the components of short-term
      plasticity in hippocampal synapses.
AB  - Studies of short-term plasticity (STP) in the hippocampus, performed mostly at
      room temperature, have shown that small central synapses rapidly depress in
      response to high-frequency stimulation. This decrease in synaptic strength with
      synapse use places constraints on the use of STP as a dynamic filter for
      processing of natural high-frequency input. Here we report that, because of a
      strong but differential temperature dependence of STP components, the properties
      of STP in excitatory hippocampal synapses change dramatically with temperature.
      By separating the contributions of various STP processes during spike trains at
      different temperatures, we found a shift from dominating depression at 23 degrees
      C to prevailing facilitation and augmentation at 33-38 degrees C. This shift of
      balance among STP components resulted from a large increase in amplitudes of
      facilitation and augmentation (Q10 approximately 2.6 and approximately 5.1,
      respectively) and little change in the amplitude of depression (Q10 approximately
      1.1) with temperature. These changes were accompanied by the accelerated decay of
      all three processes (Q10 = 3.2, 6.6, and 2.1, respectively). The balance of STP
      components achieved at higher temperatures greatly improved the maintenance of
      synaptic strength during prolonged synaptic use and had a strong effect on the
      processing of natural spike trains: a variable mixture of facilitated and
      depressed responses at 23 degrees C changed into a significantly more
      reproducible and depression-free filtering pattern at 33-38 degrees C. This
      filtering pattern was highly conserved among cells, slices, and animals, and
      under various physiological conditions, arguing for its physiological
      significance. Therefore, the fine balance among STP components, achieved only at
      near body temperatures, is required for the robust function of STP as a dynamic
      filter during natural stimulation.

PMID- 16807325
TI  - Brief bursts of parallel fiber activity trigger calcium signals in bergmann glia.
AB  - Changes in synaptic strength during ongoing activity are often mediated by
      neuromodulators. At the synapse between cerebellar granule cell parallel fibers
      (PFs) and Purkinje cells (PCs), brief bursts of stimuli can evoke endocannabinoid
      release from PCs and GABA release from interneurons that both inhibit
      transmission by activating presynaptic G-protein-coupled receptors. Studies in
      several brain regions suggest that synaptic activity can also evoke calcium
      signals in astrocytes, thereby causing them to release a transmitter, which acts
      presynaptically to regulate neurotransmitter release. In the cerebellum, Bergmann
      glia cells (BGs) are intimately associated with PF synapses. However, the
      mechanisms leading to calcium signals in BGs under physiological conditions and
      the role of BGs in regulating ongoing synaptic transmission are poorly
      understood. We found that brief bursts of PF activity evoke calcium signals in
      BGs that are triggered by the activation of metabotropic glutamate receptor 1 and
      purinergic receptors and mediated by calcium release from IP3-sensitive internal
      stores. We found no evidence for modulation of release from PFs mediated by BGs,
      even when endocannabinoid- and GABA-mediated presynaptic modulation was
      prominent. Thus, despite the fact that PF activation can reliably evoke calcium
      transients within BGs, it appears that BGs do not regulate synaptic transmission
      on the time scale of seconds to tens of seconds. Instead, endocannabinoid release
      from PCs and GABA release from molecular layer interneurons provide the primary
      means of feedback that dynamically regulate release from PF synapses.

PMID- 16807326
TI  - N-cadherin transsynaptically regulates short-term plasticity at glutamatergic
      synapses in embryonic stem cell-derived neurons.
AB  - The cell adhesion molecule N-cadherin has been proposed to regulate synapse
      formation in mammalian central neurons. This is based on its synaptic
      localization enabling alignment of presynaptic and postsynaptic specializations
      by an adhesion mechanism. However, a potential role of N-cadherin in regulating
      synaptic transmission has remained elusive. In this paper, a functional analysis
      of N-cadherin knock-out synapses was enabled by in vitro neuronal differentiation
      of mouse embryonic stem cells circumventing the early embryonic lethality of mice
      genetically null for N-cadherin. In our in vitro system, initial synapse
      formation was not altered in the absence of N-cadherin, which might be
      attributable to compensatory mechanisms. Here, we demonstrate that N-cadherin is
      required for regulating presynaptic function at glutamatergic synapses. An
      impairment in the availability of vesicles for exocytosis became apparent
      selectively during high activity. Short-term plasticity was strongly altered with
      synaptic depression enhanced in the absence of N-cadherin. Most intriguingly,
      facilitation was converted to depression under specific stimulation conditions.
      This indicates an important role of N-cadherin in the control of short-term
      plasticity. To analyze, whether N-cadherin regulates presynaptic function by a
      transsynaptic mechanism, we studied chimeric cultures consisting of wild-type
      neocortical neurons and ES cell-derived neurons. With N-cadherin absent only
      postsynaptically, we observed a similar increase in short-term synaptic
      depression as found in its complete absence. This indicates a retrograde control
      of short-term plasticity by N-cadherin. In summary, our results revealed an
      unexpected involvement of a synaptic adhesion molecule in the regulation of short
      term plasticity at glutamatergic synapses.

PMID- 16807327
TI  - GABA transporters regulate a standing GABAC receptor-mediated current at a
      retinal presynaptic terminal.
AB  - At the axon terminal of goldfish retinal bipolar cells, GABA(C) receptors have
      been shown to mediate inhibitory reciprocal synaptic currents. Here, we
      demonstrate a novel standing GABAergic current mediated exclusively by GABA(C)
      receptors. Selective inhibition of GAT-1 GABA transporters on amacrine cells
      increases this tonic current and reveals a specific functional coupling between
      GAT-1 transporters and GABA(C) receptors. We propose that this GABA(C) receptor
      mediated standing current serves to regulate synaptic gain by shunting
      depolarizing potentials that can produce Ca2+-dependent action potentials at the
      bipolar cell terminal. Furthermore, we find that the amount of GABA(C) receptor
      mediated reciprocal feedback between bipolar cell terminals and amacrine cells is
      greatly increased when GAT-1 transporters are specifically blocked by NO-711 (1
      [2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic
      acid hydrochloride). The involvement of GAT-1 transporters in regulating this
      standing (or tonic) GABA(C) current implicates them in a novel role as major
      determinants of presynaptic excitability.

PMID- 16807328
TI  - Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the
      aggregation, of both endogenous phospho- and caspase-3-cleaved tau species.
AB  - Accumulation of the microtubule-associated protein tau into neurofibrillary
      lesions is a pathological consequence of several neurodegenerative diseases,
      including Parkinson's disease and Alzheimer's disease. Hereditary mutations in
      the MAPT gene were shown to promote the formation of structurally distinct tau
      aggregates in patients that had a parkinsonian-like clinical presentation.
      Whether tau aggregates themselves or the soluble intermediate species that
      precede their aggregation are neurotoxic entities in these disorders has yet to
      be resolved; however, recent in vivo evidence supports the latter. We
      hypothesized that depletion of CHIP, a tau ubiquitin ligase, would lead to an
      increase in abnormal tau. Here, we show that deletion of CHIP in mice leads to
      the accumulation of non-aggregated, ubiquitin-negative, hyperphosphorylated tau
      species. CHIP-/- mice also have increased neuronal caspase-3 levels and activity,
      as well as caspase-cleaved tau immunoreactivity. Overexpression of mutant (P301L)
      human tau in CHIP-/- mice is insufficient to promote either argyrophilic or "pre
      tangle" structures, despite marked phospho-tau accumulation throughout the brain.
      These observations are supported in post-developmental studies using RNA
      interference for CHIP (chn-1) in Caenorhabditis elegans and cell culture systems.
      Our results demonstrate that CHIP is a primary component in the ubiquitin
      dependent degradation of tau. We also show that hyperphosphorylation and caspase
      3 cleavage of tau both occur before aggregate formation. Based on these findings,
      we propose that polyubiquitination of tau by CHIP may facilitate the formation of
      insoluble filamentous tau lesions.

PMID- 16807329
TI  - Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the
      Cerebellum.
AB  - The tight coupling between increased neuronal activity and local cerebral blood
      flow, known as functional hyperemia, is essential for normal brain function.
      However, its cellular and molecular mechanisms remain poorly understood. In the
      cerebellum, functional hyperemia depends almost exclusively on nitric oxide (NO).
      Here, we investigated the role of different neuronal populations in the control
      of microvascular tone by in situ amperometric detection of NO and infrared
      videomicroscopy of microvessel movements in rat cerebellar slices. Bath
      application of an NO donor induced both NO flux and vasodilation. Surprisingly,
      endogenous release of NO elicited by glutamate was accompanied by
      vasoconstriction that was abolished by inhibition of Ca2+-phopholipase A2 and
      impaired by cyclooxygenase and thromboxane synthase inhibition and endothelin A
      receptor blockade, indicating a role for prostanoids and endothelin 1 in this
      response. Interestingly, direct stimulation of single endothelin 1-immunopositive
      Purkinje cells elicited constriction of neighboring microvessels. In contrast to
      glutamate, NMDA induced both NO flux and vasodilation that were abolished by
      treatment with a NO synthase inhibitor or with tetrodotoxin. These findings
      indicate that NO derived from neuronal origin is necessary for vasodilation
      induced by NMDA and, furthermore, that NO-producing interneurons mediate this
      vasomotor response. Correspondingly, electrophysiological stimulation of single
      nitrergic stellate cells by patch clamp was sufficient to release NO and dilate
      both intraparenchymal and upstream pial microvessels. These findings demonstrate
      that cerebellar stellate and Purkinje cells dilate and constrict, respectively,
      neighboring microvessels and highlight distinct roles for different neurons in
      neurovascular coupling.

PMID- 16807330
TI  - Selective alterations of white matter associated with visuospatial and
      sensorimotor dysfunction in turner syndrome.
AB  - Turner syndrome (TS) is a neurogenetic disorder characterized by impaired
      spatial, numerical, and motor functioning but relatively spared verbal ability.
      Results from previous neuroimaging studies suggest that gray matter alterations
      in parietal and frontal regions may contribute to atypical visuospatial and
      executive functioning in TS. Recent findings in TS also indicate variations in
      the shape of parietal gyri and white matter microstructural anomalies of the
      temporal lobe. Diffusion tensor imaging and structural imaging methods were used
      to determine whether 10 females with TS and 10 age- and gender-matched control
      subjects exhibited differences in fractional anisotropy, white matter density,
      and local brain shape. Relative to controls, females with TS had lower fractional
      anisotropy (FA) values in the deep white matter of the left parietal-occipital
      region extending anteriorly along the superior longitudinal fasciculus into the
      deep white matter of the frontal lobe. In addition, decreased FA values were
      located bilaterally in the internal capsule extending into the globus pallidus
      and in the right prefrontal region. Voxel-based morphometry (VBM) analysis showed
      corresponding white matter density differences in the internal capsules and left
      centrum semiovale. Tensor-based morphometry analysis indicated that the FA and
      VBM results were not attributable to differences in the local shape of brain
      structures. Compared with controls, females with TS had increases in FA values
      and white matter density in language-related areas of the inferior parietal and
      temporal lobes. These complementary analyses provide evidence for alterations in
      white matter pathways that subserve affected and preserved cognitive functions in
      TS.

PMID- 16807331
TI  - Identification of an endoplasmic reticulum-retention motif in an intracellular
      loop of the kainate receptor subunit KA2.
AB  - Neuronal kainate receptors are typically heteromeric complexes composed of GluR5
      7 and KA1-2 subunits. Although GluR5-7 can exist as functional homomeric
      channels, the KA subunits cannot. KA2 is widely expressed in the CNS, and
      KA2/GluR6 heteromers are the most prevalent subunit composition in brain.
      Previous work has identified endoplasmic reticulum (ER)-retention motifs in the C
      terminus of KA2, which prevent surface expression of KA2 homomers. However, we
      find that, when these motifs are mutated, only a small fraction of KA2 is surface
      expressed. We now identify an additional ER retention motif in the intracellular
      loop region of KA2, which, when mutated together with the C-terminal motifs,
      significantly increases the level of KA2 surface expression. However,
      electrophysiological analysis of surface-expressed KA2 homomers indicates that
      they do not form functional ion channels. In heterologous cells, a large fraction
      of KA2 remains intracellular even when the trafficking motifs are mutated or when
      GluR6 is coexpressed. Therefore, we analyzed the trafficking of endogenous KA2 in
      vivo. We find that native KA2 surface expression is dramatically reduced in GluR6
      knock-out mice compared with wild-type mice. In contrast, KA2 trafficking was
      unaffected in the GluR5 knock-out. Thus, our study demonstrates that trafficking
      motifs in both the intracellular loop and C terminus regulate KA2 surface
      expression; however, in neurons, GluR6 oligomerization is required for egress of
      KA2 from the ER and transport to the cell surface. The combination of these
      mechanisms likely prevents surface expression of nonfunctional KA2 homomers and
      ensures a high level of GluR6/KA2 heteromeric kainate receptors.

PMID- 16807332
TI  - The tip-link antigen, a protein associated with the transduction complex of
      sensory hair cells, is protocadherin-15.
AB  - Sound and acceleration are detected by hair bundles, mechanosensory structures
      located at the apical pole of hair cells in the inner ear. The different elements
      of the hair bundle, the stereocilia and a kinocilium, are interconnected by a
      variety of link types. One of these links, the tip link, connects the top of a
      shorter stereocilium with the lateral membrane of an adjacent taller stereocilium
      and may gate the mechanotransducer channel of the hair cell. Mass spectrometric
      and Western blot analyses identify the tip-link antigen, a hitherto unidentified
      antigen specifically associated with the tip and kinocilial links of sensory hair
      bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as
      an avian ortholog of human protocadherin-15, a product of the gene for the
      deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15
      transcripts are shown to be expressed in the mouse inner ear, and these define
      four major isoform classes, two with entirely novel, previously unidentified
      cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing
      isoform classes reveal that each has a different spatiotemporal expression
      pattern in the developing and mature inner ear. Two isoforms are distributed in a
      manner compatible for association with the tip-link complex. An isoform located
      at the tips of stereocilia is sensitive to calcium chelation and proteolysis with
      subtilisin and reappears at the tips of stereocilia as transduction recovers
      after the removal of calcium chelators. Protocadherin-15 is therefore associated
      with the tip-link complex and may be an integral component of this structure
      and/or required for its formation.

PMID- 16807333
TI  - Mitochondrial trafficking to synapses in cultured primary cortical neurons.
AB  - Functional synapses require mitochondria to supply ATP and regulate local [Ca2+]i
      for neurotransmission. Mitochondria are thought to be transported to specific
      cellular regions of increased need such as synapses. However, little is known
      about how this occurs, including the spatiotemporal distribution of mitochondria
      relative to presynaptic and postsynaptic sites, whether mitochondria are
      dynamically recruited to synapses, and how synaptic activity affects these
      trafficking patterns. We used primary cortical neurons in culture that form
      synaptic connections and show spontaneous synaptic activity under normal
      conditions. Neurons were cotransfected with a mitochondrially targeted cyan
      fluorescent protein and an enhanced yellow fluorescent protein-tagged
      synaptophysin or postsynaptic density-95 plasmid to label presynaptic or
      postsynaptic structures, respectively. Fluorescence microscopy revealed longer
      dendritic mitochondria that occupied a greater fraction of neuronal process
      length than axonal mitochondria. Mitochondria were significantly more likely to
      be localized at synaptic sites. Although this localization was unchanged by
      inhibition of synaptic activity by tetrodotoxin, it increased in dendritic
      synapses and decreased in axonal synapses during overactivity by veratridine.
      Mitochondrial movement and recruitment to synapses also differed between axons
      and dendrites under basal conditions and when synaptic activity was altered.
      Additionally, we show that movement of dendritic mitochondria can be selectively
      impaired by glutamate and zinc. We conclude that mitochondrial trafficking to
      synapses is dynamic in neurons and is modulated by changes in synaptic activity.
      Furthermore, mitochondrial morphology and distribution may be optimized
      differentially to best serve the synaptic distributions in axons and dendrites.
      Last, selective cessation of mitochondrial movement in dendrites suggests early
      postsynaptic dysfunction in neuronal injury and degeneration.

PMID- 16807334
TI  - Lateral diffusion drives constitutive exchange of AMPA receptors at dendritic
      spines and is regulated by spine morphology.
AB  - Synapse specificity is a basic feature of synaptic plasticity, but it remains
      unclear how synapse-specific signaling is achieved if postsynaptic membrane
      proteins can diffuse laterally between synapses. We monitored movements of AMPA
      receptors (AMPARs) on the surface of mature neurons to investigate the role of
      lateral diffusion in constitutive AMPAR trafficking and to assess the influence
      of membrane architecture on the surface distribution of synaptic proteins. Our
      data show that lateral diffusion is responsible for the continual exchange of a
      substantial pool of AMPARs at the spine surface. Furthermore, we found that a
      general characteristic of membrane proteins is that their movement into and out
      of spines is slow compared with that in nonspiny membrane. This shows that
      lateral diffusion is dependent on spine morphology and is restricted at the spine
      neck. These results demonstrate the importance of lateral diffusion in
      trafficking of AMPAR protein population and provide new insight into how spine
      structure can maintain synapse specificity by compartmentalizing lateral
      diffusion and therefore increasing the residence time of membrane proteins near
      individual synapses.

PMID- 16807335
TI  - Variability of motor neuron spike timing maintains and shapes contractions of the
      accessory radula closer muscle of Aplysia.
AB  - The accessory radula closer (ARC) muscle of Aplysia has long been studied as a
      typical "slow" muscle, one that would be assumed to respond only to the overall,
      integrated spike rate of its motor neurons, B15 and B16. The precise timing of
      the individual spikes should not much matter. However, but real B15 and B16 spike
      patterns recorded in vivo show great variability that extends down to the timing
      of individual spikes. By replaying these real as well as artificially constructed
      spike patterns into ARC muscles in vitro, we examined the consequences of this
      spike-level variability for contraction. Replaying the same pattern several times
      reproduces precisely the same contraction shape: the B15/B16-ARC neuromuscular
      transform is deterministic. However, varying the timing of the spikes produces
      very different contraction shapes and amplitudes. The transform in fact operates
      at an interface between "fast" and "slow" regimens. It is fast enough that the
      timing of individual spikes greatly influences the detailed contraction shape. At
      the same time, slow integration of the spike pattern through the nonlinear
      transform allows the variable spike timing to determine also the overall
      contraction amplitude. Indeed, the variability appears to be necessary to
      maintain the contraction amplitude at a robust level. This phenomenon is tuned by
      neuromodulators that tune the speed and nonlinearity of the transform. Thus, the
      variable timing of individual spikes does matter, in at least two, functionally
      significant ways, in this "slow" neuromuscular system.

PMID- 16807338
TI  - Panic-prone state induced in rats with GABA dysfunction in the dorsomedial
      hypothalamus is mediated by NMDA receptors.
AB  - Rats with chronic inhibition of GABA synthesis and consequently enhanced
      glutamatergic excitation in the dorsomedial hypothalamus (DMH) develop panic-like
      responses, defined as tachycardia, tachypnea, hypertension, and increased anxiety
      as measured by a social interaction (SI) test, after intravenous sodium lactate
      infusions, a phenomenon similar to patients with panic disorder. Therefore, the
      present studies tested the role of the postsynaptic NMDA and AMPA type
      glutamatergic receptors in the lactate-induced panic-like responses in these
      rats. Rats were fit with femoral arterial and venous catheters and Alzet pumps
      [filled with the GABA synthesis inhibitor L-allylglycine (L-AG; 3.5 nmol/0.5
      microl per hour) or its inactive isomer D-AG] into the DMH. After 4-5 d of
      recovery only those rats with L-AG pumps exhibited panic-like responses to
      lactate infusions. Using double immunocytochemistry, we found that rats
      exhibiting panic-like responses (e.g., L-AG plus lactate) had increased c-Fos
      immunoreactivity in DMH neurons expressing the NMDA receptor 1 (NR1) subunit, but
      not those expressing the glutamate receptor 2 and 3 subunits of the AMPA
      receptors. To confirm this pharmacologically, we tested another group of rats
      implanted with l-AG pumps with intravenous lactate infusions preceded by
      injections of either NMDA [aminophosphonopentanoic acid (AP-5) or (+)-5-methyl
      10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801)] or non
      NMDA [CNQX or 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodazepin-5-yl)
      benzenamine dihydrochloride (GYKI52466)] antagonists into the DMH. Injections of
      NMDA, but not non-NMDA, antagonists into the DMH resulted in dose-dependent
      blockade of the tachycardia, tachypnea, hypertension, and SI responses after
      lactate infusions. These results suggest that NMDA, and not non-NMDA, type
      glutamate receptors regulate lactate-induced panic-like responses in rats with
      GABA dysfunction in the DMH.

PMID- 16807337
TI  - Ongoing epileptiform activity in the post-ischemic hippocampus is associated with
      a permanent shift of the excitatory-inhibitory synaptic balance in CA3 pyramidal
      neurons.
AB  - Ischemic strokes are often associated with late-onset epilepsy, but the
      underlying mechanisms are poorly understood. In the hippocampus, which is one of
      the regions most sensitive to ischemic challenge, global ischemia induces a
      complete loss of CA1 pyramidal neurons, whereas the resistant CA3 pyramidal
      neurons display a long-term hyperexcitability several months after the insult.
      The mechanisms of this long-term hyperexcitability remain unknown despite its
      clinical implication. Using chronic in vivo EEG recordings and in vitro field
      recordings in slices, we now report spontaneous interictal epileptiform
      discharges in the CA3 area of the hippocampus from post-ischemic rats several
      months after the insult. Whole-cell recordings from CA3 pyramidal neurons,
      revealed a permanent reduction in the frequency of spontaneous and miniature
      GABAergic IPSCs and a parallel increase in the frequency of spontaneous and
      miniature glutamatergic postsynaptic currents. Global ischemia also induced a
      dramatic loss of GABAergic interneurons and terminals together with an increase
      in glutamatergic terminals in the CA3 area of the hippocampus. Altogether, our
      results show a morpho-functional reorganization in the CA3 network several months
      after global ischemia, resulting in a net shift in the excitatory-inhibitory
      balance toward excitation that may constitute a substrate for the generation of
      epileptiform discharges in the post-ischemic hippocampus.

PMID- 16807339
TI  - On the role of the pontine brainstem in vocal pattern generation: a telemetric
      single-unit recording study in the squirrel monkey.
AB  - In a recent study, we localized a discrete area in the ventrolateral pontine
      brainstem of squirrel monkeys, which seems to play a role in vocal pattern
      generation of frequency-modulated vocalizations. The present study compares the
      neuronal activity of this area with that of three motoneuron pools involved in
      phonation, namely the trigeminal motor nucleus, facial nucleus, and nucleus
      ambiguous. The experiments were performed in freely moving squirrel monkeys
      (Saimiri sciureus) during spontaneous vocal communication, using a telemetric
      single-unit recording technique. We found vocalization-related activity in all
      motoneuron pools recorded. Each of them, however, showed a specific profile of
      activity properties with respect to call types uttered, syllable structure, and
      pre-onset time. Different activity profiles were also found for neurons showing
      purely vocalization-correlated activity, vocalization- and mastication-correlated
      activity, and vocalization- and respiration-correlated activity. By comparing the
      activity properties of the proposed vocal pattern generator with the three
      motoneuron pools, we show that the pontine vocalization area is, in fact, able to
      control each of the three motoneuron pools during frequency-modulated
      vocalizations. The present study thus supports the existence of a vocal pattern
      generator for frequency-modulated call types in the ventrolateral pontine
      brainstem.

PMID- 16807336
TI  - Main determinants of presynaptic Ca2+ dynamics at individual mossy fiber-CA3
      pyramidal cell synapses.
AB  - Synaptic transmission between hippocampal mossy fibers (MFs) and CA3 pyramidal
      cells exhibits remarkable use-dependent plasticity. The underlying presynaptic
      mechanisms, however, remain poorly understood. Here, we have used fluorescent
      Ca2+ indicators Fluo-4, Fluo-5F, and Oregon Green BAPTA-1 to investigate Ca2+
      dynamics in individual giant MF boutons (MFBs) in area CA3 traced from the somata
      of granule cells held in whole-cell mode. In an individual MFB, a single action
      potential induces a brief peak of free Ca2+ (estimated in the range of 8-9
      microm) followed by an elevation to approximately 320 nm, which slowly decays to
      its resting level of approximately 110 nm. Changes in the somatic membrane
      potential influence presynaptic Ca2+ entry at proximal MFBs in the hilus. This
      influence decays with distance along the axon, with a length constant of
      approximately 200 microm. In giant MFBs in CA3, progressive saturation of
      endogenous Ca2+ buffers during repetitive spiking amplifies rapid Ca2+ peaks and
      the residual Ca2+ severalfold, suggesting a causal link to synaptic facilitation.
      We find that internal Ca2+ stores contribute to maintaining the low resting Ca2+
      providing approximately 22% of the buffering/extrusion capacity of giant MFBs.
      Rapid Ca2+ release from stores represents up to 20% of the presynaptic Ca2+
      transient evoked by a brief train of action potentials. The results identify the
      main components of presynaptic Ca2+ dynamics at this important cortical synapse.

PMID- 16807340
TI  - Adenoviral-mediated modulation of Sim1 expression in the paraventricular nucleus
      affects food intake.
AB  - Haploinsufficency of Sim1, which codes for a basic helix-loop-helix-PAS (PER-ARNT
      SIM) transcription factor, causes hyperphagia in mice and humans, without
      decrease in energy expenditure. Sim1 is expressed in several areas of the brain,
      including the developing and postnatal paraventricular nucleus (PVN), a region of
      the hypothalamus that controls food intake. We have previously found that the
      number of PVN cells is decreased in Sim1+/- mice, suggesting that their
      hyperphagia is caused by a developmental mechanism. However, the possibility that
      Sim1 functions in the postnatal PVN to control food intake cannot be ruled out.
      To explore this hypothesis, we used adenoviral vectors to modulate Sim1
      expression in the postnatal PVN of wild-type mice. Unilateral stereotaxic
      injection into the PVN of an adenoviral vector producing a short hairpin RNA
      directed against Sim1 resulted in a significant increase in food intake, which
      peaked to 22% 6 d after the procedure, compared with the injection of a control
      virus. In contrast, injection of an adenovirus that expresses Sim1 induced a
      decrease in food intake that was maximal on the seventh day after the procedure,
      reaching 20%. The impact of bilateral injections of these vectors into the PVN
      was not greater than that of unilateral injections. Together, these results
      strongly suggest that Sim1 functions along a physiological pathway to control
      food intake.

PMID- 16807341
TI  - Actions and consequences in bimanual interaction are represented in different
      coordinate systems.
AB  - Moving one part of the body can generate interaction forces that tend to
      destabilize other parts of the body. However, stability is maintained by
      mechanisms that predict and actively oppose these interaction forces. When our
      body or environment changes, these anticipatory mechanisms adapt so as to
      continue to produce accurate predictions. In this study, we examine the
      acquisition of a novel predictive coordination between the arms, in a situation
      in which a force is produced on one hand as a consequence of the action of the
      other hand. Specifically, a force was applied to the left hand that depended on
      the velocity of the right hand. With practice, subjects learned to stabilize the
      perturbed left arm during right-arm movements by predicting and actively opposing
      the externally applied forces. After adaptation, we examined how learning
      generalized to a new joint configuration of the right or left arm to investigate
      the coordinate systems in which the internal transformation from movement to
      force is represented. This revealed a dissociation between the representation of
      the action of the right arm and the representation of its consequence, that is
      the force on the left arm. The movement is represented in extrinsic coordinates
      related to the velocity of the hand, whereas the force resulting from the
      movement is represented in a joint-based intrinsic coordinate system.

PMID- 16807342
TI  - Kainate receptor-mediated inhibition of glutamate release involves protein kinase
      A in the mouse hippocampus.
AB  - The mechanisms involved in the inhibition of glutamate release mediated by the
      activation of presynaptic kainate receptors (KARs) at the hippocampal mossy fiber
      CA3 synapse are not well understood. We have observed a long-lasting inhibition
      of CA3 evoked excitatory postsynaptic currents (eEPSCs) after a brief application
      of kainate (KA) at concentrations ranging from 0.3 to 10 muM. The inhibition
      outlasted the change in holding current caused by the activation of ionotropic
      KARs in CA3 pyramidal cells, indicating that this action is not contingent on the
      opening of the receptor channels. The inhibition of the eEPSCs by KA was
      prevented by G protein and protein kinase A (PKA) inhibitors and was enhanced
      after stimulation of the adenylyl cyclase (AC) with forskolin. We conclude that
      KARs present at mossy fiber terminals mediate the inhibition of glutamate release
      through a metabotropic mechanism that involves the activation of an AC-second
      messenger cAMP-PKA signaling cascade.

PMID- 16807343
TI  - A new "kine" of pain: MCP-1 and sensory neuron excitability. Focus on "MCP-1
      enhances excitability of nociceptive neurons in chronically compressed dorsal
      root ganglia".

PMID- 16807344
TI  - Vibrissa myoclonus (rhythmic retractions) driven by resonance of excitatory
      networks in motor cortex.
AB  - Rodents use rhythmic vibrissae movements to sense the environment. It is
      currently unclear whether intrinsic activity in the vibrissa motor cortex (vMI)
      is capable of driving vibrissa movements on a cycle-by-cycle basis. Disinhibition
      of vMI results in the occurrence of spontaneous 5- to 15-Hz synchronized
      oscillations. In behaving rats, this synchronous resonance of vMI is shown here
      to drive contralateral vibrissa movements that are phase-locked to each cycle of
      the oscillation. In contrast to active whisking during sensing, which consists of
      active protractions, the vibrissa movements produced by vMI oscillations
      consisted of rhythmic retractions. The results demonstrate that rhythmic motor
      cortex output is capable of driving vibrissa movements on a cycle-by-cycle basis.
      Such motor output may be primarily expressed during abnormal states such as those
      related to cortical myoclonous, tremors, and cortical seizures.

PMID- 16807345
TI  - Multiple time scales of temporal response in pyramidal and fast spiking cortical
      neurons.
AB  - Neural dynamic processes correlated over several time scales are found in vivo,
      in stimulus-evoked as well as spontaneous activity, and are thought to affect the
      way sensory stimulation is processed. Despite their potential computational
      consequences, a systematic description of the presence of multiple time scales in
      single cortical neurons is lacking. In this study, we injected fast spiking and
      pyramidal (PYR) neurons in vitro with long-lasting episodes of step-like and
      noisy, in-vivo-like current. Several processes shaped the time course of the
      instantaneous spike frequency, which could be reduced to a small number (1-4) of
      phenomenological mechanisms, either reducing (adapting) or increasing
      (facilitating) the neuron's firing rate over time. The different
      adaptation/facilitation processes cover a wide range of time scales, ranging from
      initial adaptation (<10 ms, PYR neurons only), to fast adaptation (<300 ms),
      early facilitation (0.5-1 s, PYR only), and slow (or late) adaptation (order of
      seconds). These processes are characterized by broad distributions of their
      magnitudes and time constants across cells, showing that multiple time scales are
      at play in cortical neurons, even in response to stationary stimuli and in the
      presence of input fluctuations. These processes might be part of a cascade of
      processes responsible for the power-law behavior of adaptation observed in
      several preparations, and may have far-reaching computational consequences that
      have been recently described.

PMID- 16807347
TI  - Inhibition of Nav1.7 and Nav1.4 sodium channels by trifluoperazine involves the
      local anesthetic receptor.
AB  - The calmodulin (CaM) inhibitor trifluoperazine (TFP) can produce analgesia when
      given intrathecally to rats; however, the mechanism is not known. We asked
      whether TFP could modulate the Na(v)1.7 sodium channel, which is highly expressed
      in the peripheral nervous system and plays an important role in nociception. We
      show that 500 nM and 2 muM TFP induce major decreases in Na(v)1.7 and Na(v)1.4
      current amplitudes and that 2 muM TFP causes hyperpolarizing shifts in the steady
      state inactivation of Na(v)1.7 and Na(v)1.4. CaM can bind to the C-termini of
      voltage-gated sodium channels and modulate their functional properties; therefore
      we investigated if TFP modulation of sodium channels was due to CaM inhibition.
      However, the TFP inhibition was not replicated by whole cell dialysis of a
      calmodulin inhibitory peptide, indicating that major effects of TFP do not
      involve a disruption of CaM-channel interactions. Rather, our data show that TFP
      inhibition is state dependent and that the majority of the TFP inhibition depends
      on specific amino-acid residues in the local anesthetic receptor site in sodium
      channels. TFP was also effective in vivo in causing motor and sensory blockade
      after subfascial injection to the rat sciatic nerve. The state-dependent block of
      Na(v)1.7 channels with nanomolar concentrations of TFP raises the possibility
      that TFP, or TFP analogues, might be useful for regional anesthesia and pain
      management and could be more potent than traditional local anesthetics.

PMID- 16807348
TI  - Inhibitory postsynaptic potentials in lumbar motoneurons remain depolarizing
      after neonatal spinal cord transection in the rat.
AB  - GABA and glycine are excitatory in the immature spinal cord and become inhibitory
      during development. The shift from depolarizing to hyperpolarizing inhibitory
      postsynaptic potentials (IPSPs) occurs during the perinatal period in the rat, a
      time window during which the projections from the brain stem reach the lumbar
      enlargement. In this study, we investigated the effects of suppressing influences
      of the brain on lumbar motoneurons during this critical period for the negative
      shift of the reversal potential of IPSPs (E(IPSP)). The spinal cord was
      transected at the thoracic level on the day of birth [postnatal day 0 (P0)].
      E(IPSP), at P4-P7, was significantly more depolarized in cord-transected than in
      cord-intact animals (E(IPSP) above and below resting potential, respectively).
      E(IPSP) at P4-P7 in cord-transected animals was close to E(IPSP) at P0-P2. K-Cl
      cotransporter KCC2 immunohistochemistry revealed a developmental increase of
      staining in the area of lumbar motoneurons between P0 and P7 in cord-intact
      animals; this increase was not observed after spinal cord transection. The
      motoneurons recorded from cord-transected animals were less sensitive to the
      experimental manipulations aimed at testing the functionality of the KCC2 system,
      which is sensitive to [K(+)](o) and blocked by bumetanide. Although bumetanide
      significantly depolarized E(IPSP), the shift was less pronounced than in cord
      intact animals. In addition, a reduction of [K(+)](o) affected E(IPSP)
      significantly only in cord-intact animals. Therefore influences from the brain
      stem may play an essential role in the maturation of inhibitory synaptic
      transmission, possibly by upregulating KCC2 and its functionality.

PMID- 16807346
TI  - Ionic mechanism underlying recovery of rhythmic activity in adult isolated
      neurons.
AB  - Neurons exhibit long-term excitability changes necessary for maintaining proper
      cell and network activity in response to various inputs and perturbations. For
      instance, the adult crustacean pyloric network can spontaneously recover rhythmic
      activity after complete shutdown resulting from permanent removal of
      neuromodulatory inputs. Dissociated lobster stomatogastric ganglion (STG) neurons
      have been shown to spontaneously develop oscillatory activity via excitability
      changes. Rhythmic electrical stimulation can eliminate these oscillatory patterns
      in some cells. The ionic mechanisms underlying these changes are only partially
      understood. We used dissociated crab STG neurons to study the ionic mechanisms
      underlying spontaneous recovery of rhythmic activity and stimulation-induced
      activity changes. Similar to lobster neurons, rhythmic activity spontaneously
      develops in crab STG neurons. Rhythmic hyperpolarizing stimulation can eliminate,
      but more commonly accelerate, the emergence of stable oscillatory activity
      depending on Ca(2+) influx at hyperpolarized voltages. Our main finding is that
      upregulation of a Ca(2+) current and downregulation of a high-threshold K(+)
      current underlies the spontaneous homeostatic development of oscillatory
      activity. However, because of a nonlinear dependence on stimulus frequency,
      hyperpolarization-induced oscillations appear to be inconsistent with a
      homeostatic regulation of activity. We find no difference in the activity
      patterns or the underlying ionic currents involved between neurons of the fast
      pyloric and the slow gastric mill networks during the first 10 days in isolation.
      Dynamic-clamp experiments confirm that these conductance modifications can
      explain the observed activity changes. We conclude that spontaneous and
      stimulation-induced excitability changes in STG neurons can both result in
      intrinsic oscillatory activity via regulation of the same two conductances.

PMID- 16807351
TI  - Operant conditioning of reciprocal inhibition in rat soleus muscle.
AB  - Operant conditioning of the H-reflex, the electrical analog of the spinal stretch
      reflex (SSR), induces activity-dependent plasticity in the spinal cord and might
      be used to improve locomotion after spinal cord injury. To further assess the
      potential clinical significance of spinal reflex conditioning, this study asks
      whether another well-defined spinal reflex pathway, the disynaptic pathway
      underlying reciprocal inhibition (RI), can also be operantly conditioned. Sprague
      Dawley rats were implanted with electromyographic (EMG) electrodes in right
      soleus (SOL) and tibialis anterior (TA) muscles and a stimulating cuff on the
      common peroneal (CP) nerve. When background EMG in both muscles remained in
      defined ranges, CP stimulation elicited the TA H-reflex and SOL RI. After
      collection of control data for 20 days, each rat was exposed for 50 days to up
      conditioning (RIup mode) or down-conditioning (RIdown mode) in which food reward
      occurred if SOL RI evoked by CP stimulation was more (RIup mode) or less (RIdown
      mode) than a criterion. TA and SOL background EMG and TA M response remained
      stable. In every rat, RI conditioning was successful (i.e., change > or =20% in
      the correct direction). In the RIup rats, final SOL RI averaged 171+/- 28% (mean
      +/- SE) of control, and final TA H-reflex averaged 114 +/- 14%. In the RIdown
      rats, final SOL RI averaged 37 +/- 13% of control, and final TA H-reflex averaged
      60 +/- 18%. Final SOL RI and TA H-reflex sizes were significantly correlated.
      Thus like the SSR and the H-reflex, RI can be operantly conditioned; and
      conditioning one reflex can affect another reflex as well.

PMID- 16807349
TI  - Phase locking of auditory-nerve fibers to the envelopes of high-frequency sounds:
      implications for sound localization.
AB  - Although listeners are sensitive to interaural time differences (ITDs) in the
      envelope of high-frequency sounds, both ITD discrimination performance and the
      extent of lateralization are poorer for high-frequency sinusoidally amplitude
      modulated (SAM) tones than for low-frequency pure tones. Psychophysical studies
      have shown that ITD discrimination at high frequencies can be improved by using
      novel transposed-tone stimuli, formed by modulating a high-frequency carrier by a
      half-wave-rectified sinusoid. Transposed tones are designed to produce the same
      temporal discharge patterns in high-characteristic frequency (CF) neurons as
      occur in low-CF neurons for pure-tone stimuli. To directly test this hypothesis,
      we compared responses of auditory-nerve fibers in anesthetized cats to pure
      tones, SAM tones, and transposed tones. Phase locking was characterized using
      both the synchronization index and autocorrelograms. With both measures, phase
      locking was better for transposed tones than for SAM tones, consistent with the
      rationale for using transposed tones. However, phase locking to transposed tones
      and that to pure tones were comparable only when all three conditions were met:
      stimulus levels near thresholds, low modulation frequencies (<250 Hz), and low
      spontaneous discharge rates. In particular, phase locking to both SAM tones and
      transposed tones substantially degraded with increasing stimulus level, while
      remaining more stable for pure tones. These results suggest caution in assuming a
      close similarity between temporal patterns of peripheral activity produced by
      transposed tones and pure tones in both psychophysical studies and
      neurophysiological studies of central neurons.

PMID- 16807350
TI  - Endocannabinoid-mediated depolarization-induced suppression of inhibition in
      hilar mossy cells of the rat dentate gyrus.
AB  - Hilar mossy cells represent a unique population of local circuit neurons in the
      hippocampus and dentate gyrus. Here we use electrophysiological techniques in
      acute preparations of hippocampal slices to demonstrate that depolarization of a
      single hilar mossy cell can produce robust inhibition of local GABAergic
      afferents. This depolarization-induced suppression of inhibition (DSI) can be
      observed as a transient reduction in frequency of spontaneous inhibitory
      postsynaptic currents (sIPSCs) or as a transient reduction in amplitude of evoked
      IPSCs (eIPSCs). We find that DSI of eIPSCs as observed in hilar mossy cells is
      enhanced by activation of muscarinic acetylcholine receptors, blocked by
      chelation of postsynaptic calcium, and critically dependent on retrograde
      activation of presynaptic cannabinoid type 1 (CB1) receptors. We further report
      that activation of CB1 receptors on GABAergic afferents to hilar mossy cells (by
      either endogenous or exogenous agonists) preferentially inhibits calcium
      dependent exocytosis and that endocannabinoid-dependent retrograde signaling in
      this system is subject to tight spatial constraints.

PMID- 16807352
TI  - Contribution of persistent Na+ current and M-type K+ current to somatic bursting
      in CA1 pyramidal cells: combined experimental and modeling study.
AB  - The intrinsic firing modes of adult CA1 pyramidal cells vary along a continuum of
      "burstiness" from regular firing to rhythmic bursting, depending on the ionic
      composition of the extracellular milieu. Burstiness is low in neurons exposed to
      a normal extracellular Ca(2+) concentration ([Ca(2+)](o)), but is markedly
      enhanced by lowering [Ca(2+)](o), although not by blocking Ca(2+) and Ca(2+)
      activated K(+) currents. We show, using intracellular recordings, that burstiness
      in low [Ca(2+)](o) persists even after truncating the apical dendrites,
      suggesting that bursts are generated by an interplay of membrane currents at or
      near the soma. To study the mechanisms of bursting, we have constructed a
      conductance-based, one-compartment model of CA1 pyramidal neurons. In this neuron
      model, reduced [Ca(2+)](o) is simulated by negatively shifting the activation
      curve of the persistent Na(+) current (I(NaP)) as indicated by recent
      experimental results. The neuron model accounts, with different parameter sets,
      for the diversity of firing patterns observed experimentally in both zero and
      normal [Ca(2+)](o). Increasing I(NaP) in the neuron model induces bursting and
      increases the number of spikes within a burst but is neither necessary nor
      sufficient for bursting. We show, using fast-slow analysis and bifurcation
      theory, that the M-type K(+) current (I(M)) allows bursting by shifting neuronal
      behavior between a silent and a tonically active state provided the kinetics of
      the spike generating currents are sufficiently, although not extremely, fast. We
      suggest that bursting in CA1 pyramidal cells can be explained by a single
      compartment "square bursting" mechanism with one slow variable, the activation of
      I(M).

PMID- 16807353
TI  - Nuclear localization of PTEN by a Ran-dependent mechanism enhances apoptosis:
      Involvement of an N-terminal nuclear localization domain and multiple nuclear
      exclusion motifs.
AB  - The targeting of the tumor suppressor PTEN protein to distinct subcellular
      compartments is a major regulatory mechanism of PTEN function, by controlling its
      access to substrates and effector proteins. Here, we investigated the molecular
      basis and functional consequences of PTEN nuclear/cytoplasmic distribution. PTEN
      accumulated in the nucleus of cells treated with apoptotic stimuli. Nuclear
      accumulation of PTEN was enhanced by mutations targeting motifs in distinct PTEN
      domains, and it was dependent on an N-terminal nuclear localization domain.
      Coexpression of a dominant negative Ran GTPase protein blocked PTEN accumulation
      in the nucleus, which was also affected by coexpression of importin alpha
      proteins. The lipid- and protein-phosphatase activity of PTEN differentially
      modulated PTEN nuclear accumulation. Furthermore, catalytically active nuclear
      PTEN enhanced cell apoptotic responses. Our findings indicate that multiple
      nuclear exclusion motifs and a nuclear localization domain control PTEN nuclear
      localization by a Ran-dependent mechanism and suggest a proapoptotic role for
      PTEN in the cell nucleus.

PMID- 16807354
TI  - Measuring nanometer scale gradients in spindle microtubule dynamics using model
      convolution microscopy.
AB  - A computational model for the budding yeast mitotic spindle predicts a spatial
      gradient in tubulin turnover that is produced by kinetochore-attached microtubule
      (kMT) plus-end polymerization and depolymerization dynamics. However, kMTs in
      yeast are often much shorter than the resolution limit of the light microscope,
      making visualization of this gradient difficult. To overcome this limitation, we
      combined digital imaging of fluorescence redistribution after photobleaching
      (FRAP) with model convolution methods to compare computer simulations at
      nanometer scale resolution to microscopic data. We measured a gradient in
      microtubule dynamics in yeast spindles at approximately 65-nm spatial intervals.
      Tubulin turnover is greatest near kinetochores and lowest near the spindle poles.
      A beta-tubulin mutant with decreased plus-end dynamics preserves the spatial
      gradient in tubulin turnover at a slower time scale, increases average
      kinetochore microtubule length approximately 14%, and decreases tension at
      kinetochores. The beta-tubulin mutant cells have an increased frequency of
      chromosome loss, suggesting that the accuracy of chromosome segregation is linked
      to robust kMT plus-end dynamics.

PMID- 16807358
TI  - Y(4) receptors mediate the inhibitory responses of pancreatic polypeptide in
      human and mouse colon mucosa.
AB  - The antisecretory effects of several Y agonists, including pancreatic polypeptide
      (PP), indicate the presence of Y(1), Y(2), and Y(4) receptors in mouse and human
      (h) colon mucosae. Here, we used preparations from human and from wild-type (WT),
      Y(4), and Y(1) receptor knockout ((-/-)) mice, alongside Y(4) receptor
      transfected cells to define the relative functional contribution of the Y(4)
      receptor. First, rat (r) PP antisecretory responses were lost in murine Y(4)(-/-)
      preparations, but hPP and Pro(34) peptide YY (PYY) costimulated Y(4) and Y(1)
      receptors in WT mucosa. The Y(1) antagonist/Y(4) agonist GR231118
      [(Ile,Glu,Pro,Dpr,Tyr,Arg,Leu,Arg,Try-NH(2))-2-cyclic(2,4'),(2',4)-diamide]
      elicited small Y(4)-mediated antisecretory responses in human tissues pretreated
      with the Y(1) antagonist, BIBO3304 [(R)-N-[[4-(aminocarbonylaminomethyl)
      phenyl]methyl]-N(2)-(diphenylacetyl)-argininamide trifluoroacetate)], and
      attenuated Y(4)-mediated hPP responses in mouse and human mucosa. GR231118 and
      rPP were also antisecretory in hY(4)-transfected epithelial monolayers but were
      partial agonists compared with hPP at this receptor. In Y(4)-transfected human
      embryonic kidney (HEK) 293 cells, Y(4) ligands displaced [(125)I]hPP binding with
      orders of affinity (pK(i)) at human (hPP = rPP > GR231118 > Pro(34)PYY = PYY) and
      mouse (rPP = hPP > GR231118 > Pro(34)PYY > PYY) Y(4) receptors. GR231118- and rPP
      stimulated guanosine 5'-3-O-(thio)triphosphate binding through hY(4) receptors
      with significantly lower efficacy than hPP. GR231118 marginally increased basal
      but abolished further PP-induced hY(4) internalization to recycling (transferrin
      labeled) pathways in HEK293 cells. Taken together, these findings show that Y(4)
      receptors play a definitive role in attenuating colonic anion transport and may
      be useful targets for novel antidiarrheal agents due to their limited peripheral
      expression.

PMID- 16807355
TI  - Sir2 represses endogenous polymerase II transcription units in the ribosomal DNA
      nontranscribed spacer.
AB  - Silencing at the rDNA, HM loci, and telomeres in Saccharomyces cerevisiae
      requires histone-modifying enzymes to create chromatin domains that are
      refractory to recombination and RNA polymerase II transcription machineries. To
      explore how the silencing factor Sir2 regulates the composition and function of
      chromatin at the rDNA, the association of histones and RNA polymerase II with the
      rDNA was measured by chromatin immunoprecipitation. We found that Sir2 regulates
      not only the levels of K4-methylated histone H3 at the rDNA but also the levels
      of total histone H3 and RNA polymerase II. Furthermore, our results demonstrate
      that the ability of Sir2 to limit methylated histones at the rDNA requires its
      deacetylase activity. In sir2Delta cells, high levels of K4-trimethylated H3 at
      the rDNA nontranscribed spacer are associated with the expression of
      transcription units in the nontranscribed spacer by RNA polymerase II and with
      previously undetected alterations in chromatin structure. Together, these data
      suggest a model where the deacetylase activity of Sir2 prevents
      euchromatinization of the rDNA and silences naturally occurring intergenic
      transcription units whose expression has been associated with disruption of
      cohesion complexes and repeat amplification at the rDNA.

PMID- 16807357
TI  - Translocation of endothelial nitric-oxide synthase involves a ternary complex
      with caveolin-1 and NOSTRIN.
AB  - Recently, we characterized a novel endothelial nitric-oxide synthase (eNOS)
      interacting protein, NOSTRIN (for eNOS-trafficking inducer), which decreases eNOS
      activity upon overexpression and induces translocation of eNOS away from the
      plasma membrane. Here, we show that NOSTRIN directly binds to caveolin-1, a well
      established inhibitor of eNOS. Because this interaction occurs between the N
      terminus of caveolin (positions 1-61) and the central domain of NOSTRIN
      (positions 323-434), it allows for independent binding of each of the two
      proteins to eNOS. Consistently, we were able to demonstrate the existence of a
      ternary complex of NOSTRIN, eNOS, and caveolin-1 in Chinese hamster ovary (CHO)
      eNOS cells. In human umbilical vein endothelial cells (HUVECs), the ternary
      complex assembles at the plasma membrane upon confluence or thrombin stimulation.
      In CHO-eNOS cells, NOSTRIN-mediated translocation of eNOS involves caveolin in a
      process most likely representing caveolar trafficking. Accordingly, trafficking
      of NOSTRIN/eNOS/caveolin is affected by altering the state of actin filaments or
      cholesterol levels in the plasma membrane. During caveolar trafficking, NOSTRIN
      functions as an adaptor to recruit mediators such as dynamin-2 essential for
      membrane fission. We propose that a ternary complex between NOSTRIN, caveolin-1,
      and eNOS mediates translocation of eNOS, with important implications for the
      activity and availability of eNOS in the cell.

PMID- 16807356
TI  - The Nup107-160 nucleoporin complex is required for correct bipolar spindle
      assembly.
AB  - The Nup107-160 complex is a critical subunit of the nuclear pore. This complex
      localizes to kinetochores in mitotic mammalian cells, where its function is
      unknown. To examine Nup107-160 complex recruitment to kinetochores, we stained
      human cells with antisera to four complex components. Each antibody stained not
      only kinetochores but also prometaphase spindle poles and proximal spindle
      fibers, mirroring the dual prometaphase localization of the spindle checkpoint
      proteins Mad1, Mad2, Bub3, and Cdc20. Indeed, expanded crescents of the Nup107
      160 complex encircled unattached kinetochores, similar to the hyperaccumulation
      observed of dynamic outer kinetochore checkpoint proteins and motors at
      unattached kinetochores. In mitotic Xenopus egg extracts, the Nup107-160 complex
      localized throughout reconstituted spindles. When the Nup107-160 complex was
      depleted from extracts, the spindle checkpoint remained intact, but spindle
      assembly was rendered strikingly defective. Microtubule nucleation around sperm
      centrosomes seemed normal, but the microtubules quickly disassembled, leaving
      largely unattached sperm chromatin. Notably, Ran-GTP caused normal assembly of
      microtubule asters in depleted extracts, indicating that this defect was upstream
      of Ran or independent of it. We conclude that the Nup107-160 complex is dynamic
      in mitosis and that it promotes spindle assembly in a manner that is distinct
      from its functions at interphase nuclear pores.

PMID- 16807360
TI  - Acid-induced release of platelet-activating factor by human esophageal mucosa
      induces inflammatory mediators in circular smooth muscle.
AB  - In a human in vitro model of esophagitis, we investigated the genesis of
      esophagitis-associated dysmotility by examining HCl-induced production of
      inflammatory mediators in the mucosa and investigating their effect on esophageal
      circular muscle. Muscularis propria was removed from organ donors' esophagi,
      leaving the mucosal tube intact. The tube was tied at both ends, forming a sac,
      and filled with HCl at pH 4. After 3 h of incubation, the supernatant surrounding
      the sac was analyzed or applied to circular muscle strips. HCl alone did not
      affect circular muscle contraction in response to electrical field stimulation
      (EFS), but supernatant of HCl-treated mucosa abolished contraction. The
      inhibition was reversed by the platelet-activating factor (PAF) antagonist CV3988
      [(+/-)-3-(N-octadecylcarbamoyl)-2-methoxy) propyl-(2-thiazolioethyl) phosphate],
      whereas the PAF analog 2-O-methyl platelet-activating factor C-16 (PAF-16)
      inhibited EFS-induced contraction and acetylcholine (ACh) release in circular
      muscle strips. The hydrogen peroxide scavenger catalase reversed the inhibition
      in contraction, to the same extent as CV3988. We therefore measured PAF and
      hydrogen peroxide (H(2)O(2)) in mucosa, mucosa supernatant, and circular muscle.
      HCl increased PAF and interleukin (IL)-1beta (but not IL-6, prostaglandin E(2),
      or H(2)O(2)) in mucosa, and only PAF was released into the supernatant,
      presumably to affect circular muscle. In circular muscle, exogenous PAF induced
      sequential formation of IL-6, H(2)O(2), IL-1beta, and PAF. Release of PAF by the
      mucosa inhibits ACh release from circular muscle layer neurons and initiates
      sequential formation of inflammatory mediators in muscle, resulting in production
      of PAF by the muscle itself, possibly initiating in a self-sustaining cycle.

PMID- 16807359
TI  - Interleukin-10 protects lipopolysaccharide-induced neurotoxicity in primary
      midbrain cultures by inhibiting the function of NADPH oxidase.
AB  - The role of anti-inflammatory cytokines in Parkinson's disease is not completely
      understood. In this study, using mesencephalic neuron-glia cultures, we report
      that both pretreatment and post-treatment of rat mesencephalic neuron-glia
      cultures with interleukin (IL)-10, a natural immune modulator, reduced
      lipopolysaccharide (LPS)-induced DA neurotoxicity. The main purpose of this study
      was to elucidate the molecular mechanism underlying IL-10-elicited
      neuroprotection. IL-10 significantly inhibited LPS-induced production of tumor
      necrosis factor-alpha, nitric oxide, and extracellular superoxide in microglia
      cells. In addition, using reconstituted neuron and glia cell cultures, IL-10 was
      shown to be neuroprotective only in the presence of microglia. More importantly,
      IL-10 failed to protect DA neurons in cultures from mice lacking NADPH oxidase
      (PHOX), a key enzyme for extracellular superoxide production in immune cells,
      suggesting the critical role of PHOX in IL-10 neuroprotection. This conclusion
      was further supported by the finding that IL-10 inhibited LPS-induced
      translocation of the cytosolic subunit of NADPH oxidase p47(phox) to the
      membrane. When the Janus tyrosine kinase (JAK) 1 signaling pathway was blocked,
      IL-10 failed to attenuate LPS-induced superoxide production, indicating that the
      JAK1 signaling cascade mediates the inhibitory effect of IL-10. Together, our
      results suggest that IL-10 inhibits LPS-induced DA neurotoxicity through the
      inhibition of PHOX activity in a JAK1-dependent mechanism.

PMID- 16807361
TI  - Intracellular delivery of the p38 mitogen-activated protein kinase inhibitor
      SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in
      renal tubular cells: a novel strategy to treat renal fibrosis.
AB  - During renal injury, activation of p38 mitogen-activated protein kinase (MAPK) in
      proximal tubular cells plays an important role in the inflammatory events that
      eventually lead to renal fibrosis. We hypothesized that local inhibition of p38
      within these cells may be an interesting approach for the treatment of renal
      fibrosis. To effectuate this, we developed a renal-specific conjugate of the p38
      inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H
      imidazole] and the carrier lysozyme. First, we demonstrated that SB202190
      inhibited the expression of albumin-induced proinflammatory (monocyte
      chemoattractant protein-1) and transforming growth factor (TGF)-beta1-induced
      profibrotic (procollagen-Ialpha1) genes over 50% in renal tubular cells (normal
      rat kidney-52E). Next, we conjugated SB202190 via a carbamate linkage to
      lysozyme. However, this conjugate rapidly released the drug upon incubation in
      serum. Therefore, we applied a new platinum(II)-based linker approach, the so
      called universal linkage system (ULS), which forms a coordinative bond with
      SB202190. The SB202190-ULS-lysozyme remained stable in serum but released the
      drug in kidney homogenates. SB202190-ULS-lysozyme accumulated efficiently in
      renal tubular cells and provided a local drug reservoir during a period of 3 days
      after a single intravenous injection. Treatment with SB202190-ULS-lysozyme
      inhibited TGF-beta1-induced gene expression for procollagen-Ialpha1 by 64% in HK
      2 cells. Lastly, we evaluated the efficacy of a single dose of the conjugate in
      the unilateral renal ischemia-reperfusion rat model. A reduction of intrarenal
      p38 phosphorylation and alpha-smooth muscle actin protein expression was observed
      4 days after the ischemia-reperfusion injury. In conclusion, we have developed a
      novel strategy for local delivery of the p38 MAPK inhibitor SB202190, which may
      be of use in the treatment of renal fibrosis.

PMID- 16807362
TI  - Differential effects of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5
      pyridyl]carbamoyl]-6-trifluoromethylindone (SB 243213) on 5-hydroxytryptamine(2C)
      receptor-mediated responses.
AB  - 5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6
      trifluoromethylindone (SB 243213) is a selective, high-affinity 5
      hydroxytryptamine (serotonin)(2C) receptor ligand that has been previously
      characterized as a competitive 5-HT(2C) receptor antagonist that has a long
      duration of activity in vivo. It is active in two preclinical models of anxiety
      and has an improved anxiolytic profile compared with benzodiazepines. In this
      study, we further characterized the pharmacological properties of SB 243213 by
      measuring its effects on each of multiple responses coupled to the 5-HT(2C)
      receptor. In Chinese hamster ovary cells, SB 243213 was an inverse agonist for
      the phospholipase A(2) response, for guanosine 5'-O-(3-[(35)S]thio)triphosphate
      binding, for reduction of constitutive desensitization, and for enhancement of
      dopamine release in the rat nucleus accumbens, with relative efficacies of 0.6,
      1, 1, and 0.6, respectively. However, for the phospholipase C (PLC) signaling
      cascade, SB 243213 behaved as an antagonist. Although SB 243213 was previously
      characterized as a competitive antagonist for the PLC response, the magnitude of
      the dextral shift of the 5-HT concentration-response curve was time-dependent,
      and the maximal PLC response to 5-HT was decreased, probably as a result of the
      slow dissociation rate of SB 243213 (initial dissociation rate was 3.2 times
      slower than SB206553, a prototypical 5-HT(2C) receptor inverse agonist). Taken
      together, these data show that the pharmacological characteristics of SB 243213
      at the 5-HT(2C) receptor differ depending upon the response measured, and they
      support the hypothesis that different drugs, acting at the same receptor subtype,
      can differentially regulate multiple cellular signaling systems.

PMID- 16807363
TI  - An isoflurane- and alcohol-insensitive mutant GABA(A) receptor alpha(1) subunit
      with near-normal apparent affinity for GABA: characterization in heterologous
      systems and production of knockin mice.
AB  - Volatile anesthetics and alcohols enhance transmission mediated by gamma
      aminobutyric acid type A receptors (GABA(A)Rs) in the central nervous system, an
      effect that may underlie some of the behavioral actions of these agents.
      Substituting a critical serine residue within the GABA(A)R alpha(1) subunit at
      position 270 with the larger residue histidine eliminated receptor modulation by
      isoflurane, but it also affected receptor gating (increased GABA sensitivity). To
      correct the shift in GABA sensitivity of this mutant, we mutated a second
      residue, leucine at position 277 to alanine. The double mutant
      alpha(1)(S270H,L277A)beta(2)gamma(2S) GABA(A)R was expressed in Xenopus laevis
      oocytes and human embryonic kidney (HEK)293 cells, and it had near-normal GABA
      sensitivity. However, rapid application of a brief GABA pulse to receptors
      expressed in HEK293 cells revealed that the deactivation was faster in double
      mutant than in wild-type receptors. In all heterologous systems, the enhancing
      effect of isoflurane and ethanol was greatly decreased in the double mutant
      receptor. Homozygous knockin mice harboring the double mutation were viable and
      presented no overt abnormality, except hyperactivity. This knockin mouse line
      should be useful in determining which behavioral actions of volatile anesthetics
      and ethanol are mediated by the GABA(A)Rs containing the alpha(1) subunit.

PMID- 16807364
TI  - Inhibition of the enzymatic activity of heme oxygenases by azole-based antifungal
      drugs.
AB  - Ketoconazole (KTZ) and other azole antifungal agents are known to have a variety
      of actions beyond the inhibition of sterol synthesis in fungi. These drugs share
      structural features with a series of novel heme oxygenase (HO) inhibitors
      designed in our laboratory. Accordingly, we hypothesized that therapeutically
      used azole-based antifungal drugs are effective HO inhibitors. Using gas
      chromatography to quantify carbon monoxide formation in vitro and in vivo, we
      have shown that azole-containing antifungal drugs are potent HO inhibitors.
      Terconazole, sulconazole, and KTZ were the most potent drugs with IC(50) values
      of 0.41 +/- 0.01, 1.1 +/- 0.4, and 0.3 +/- 0.1 microM for rat spleen microsomal
      HO activity, respectively. Kinetic characterization revealed that KTZ was a
      noncompetitive HO inhibitor. In the presence of KTZ (2.5 and 10 microM), K(m)
      values for both rat spleen and brain microsomal HO were not altered; however, a
      significant decrease in the catalytic capacity (V(max)) was observed (P < 0.005).
      KTZ was also found to weakly inhibit nitric-oxide synthase with an IC(50) of 177
      +/- 2 microM but had no effect on the enzymatic activity of NADPH cytochrome P450
      reductase. Because these drugs were effective within the concentration range
      observed in humans, it is possible that inhibition of HO may play a role in some
      of the pharmacological actions of these antimycotic drugs.

PMID- 16807365
TI  - A gene-targeting approach for functional characterization of KIAA genes encoding
      extremely large proteins.
AB  - Given that thousands of genes exist in the mammalian genome, criteria are needed
      to prioritize their functional analysis and to decrease the likelihood of
      producing gene-targeted mice that lack overt phenotypes. Initial analysis efforts
      are likely to be fruitful if focused on genes encoding large proteins, since at
      least some large proteins serve as frameworks for intricate assembly of protein
      complexes, and their inactivation would render definitive, observable phenotypes.
      Here, we describe the functional characterization of the murine homologues of
      five human KIAA genes (KIAA1409, KIAA1440, KIAA1447, KIAA1768, and KIAA1276) that
      encode large proteins. Gene-targeted mice had phenotypic and developmental
      defects resulting from the functional deletion of three of these five genes. Mice
      with targeted disruption of KIAA1409 lacked the ability to drink, and those with
      targeted disruption of KIAA1447 displayed hind leg motor dysfunction. Disruption
      of KIAA1440 led to embryonic lethality at the blastocyst stage. The high success
      rate of our approach demonstrates the rationale for the genome-wide functional
      examination of large proteins in mice using reverse genetics.

PMID- 16807366
TI  - Improved lung growth and function through hypoxia-inducible factor in primate
      chronic lung disease of prematurity.
AB  - Bronchopulmonary dysplasia (BPD), a chronic lung disease affecting preterm
      neonates, is associated with significant childhood and adult health problems.
      Histopathologic features of BPD include impaired vascular and distal airway
      development. We previously showed that activation of hypoxia-inducible factors
      (HIFs) by inhibition of prolyl hydroxylase domain-containing proteins (PHDs) is
      feasible and that it stimulates vascular endothelial growth factor (VEGF)
      dependent angiogenesis in vitro. We tested the hypothesis that enhancement of
      angiogenesis by activation of HIFs improves lung growth and function in
      prematurely born neonates in vivo. Preterm baboons (125 day+14 day pro re nata O2
      model, corresponding to 27 human gestational weeks) were treated for 14 days with
      intravenous (i.v.) FG-4095, a PHD inhibitor. Notably, 77% of diminished total
      alveolar surface area in untreated controls was recovered by FG-4095 treatment.
      Functional significance of the structural changes was indicated by improved
      oxygenation and lung compliance in FG-4095-treated newborns. Surfactant proteins
      B and C and saturated phosphatidylcholine were unchanged. Incidence of
      spontaneous ductus arteriosus closure was increased, likely contributing to lower
      ratio of pulmonary to systemic blood flow in FG-4095 group. These findings
      indicate that HIF stimulation by PHD inhibition ameliorates pathological and
      physiological consequences of BPD.

PMID- 16807367
TI  - Vascularization and engraftment of a human skin substitute using circulating
      progenitor cell-derived endothelial cells.
AB  - We seeded tissue engineered human skin substitutes with endothelial cells (EC)
      differentiated in vitro from progenitors from umbilical cord blood (CB-EC) or
      adult peripheral blood (AB-EC), comparing the results to previous work using
      cultured human umbilical vein EC (HUVEC) with or without Bcl-2 transduction.
      Vascularized skin substitutes were prepared by seeding Bcl-2-transduced or
      nontransduced HUVEC, CB-EC, or AB-EC on the deep surface of decellularized human
      dermis following keratinocyte coverage of the epidermal surface. These skin
      substitutes were transplanted onto C.B-17 SCID/beige mice receiving systemic
      rapamycin or vehicle control and were analyzed 21 d later. CB-EC and Bcl-2-HUVEC
      formed more human EC-lined vessels than AB-EC or control HUVEC; CB-EC, Bcl-2
      HUVEC, and AB-EC but not control HUVEC promoted ingrowth of mouse EC-lined
      vessels. Bcl-2 transduction increased the number of human and mouse EC-lined
      vessels in grafts seeded with HUVEC but not with CB-EC or AB-EC. Both CB-EC and
      AB-EC-induced microvessels became invested by smooth muscle cell-specific alpha
      actin-positive mural cells, indicative of maturation. Rapamycin inhibited
      ingrowth of mouse EC-lined vessels but did not inhibit formation of human EC
      lined vessels. We conclude that EC differentiated from circulating progenitors
      can be utilized to vascularize human skin substitutes even in the setting of
      compromised host angiogenesis/vasculogenesis.

PMID- 16807368
TI  - Overexpression of FasL in retinal pigment epithelial cells reduces choroidal
      neovascularization.
AB  - Choroidal neovascularization (CNV) is responsible for the severe visual loss in
      age-related macular degeneration. CNV formation is considered to be due to an
      imbalance between pro- and antiangiogenic factors that lead to neovascular growth
      from the choriocapillaris into the subretinal space. To define whether FasL
      overexpression in retinal pigment epithelial cells (RPE) can inhibit choroidal
      neovascularization through Fas-FasL-mediated apoptosis, we examined the role of
      this pathway in a mouse model of laser-induced choroidal neovascularization. FasL
      was expressed in the retinal pigment epithelium of transgenic mice. Polymerase
      chain reaction (PCR), immunoblot, and immunohistochemistry confirmed that the
      transgene FasL was specifically expressed in RPE. The established laser model was
      used to induce choroidal neovascularization (CNV) in wild-type (WT) and
      transgenic mice. CNV formation was compared with respect to fluorescein
      angiographic leakage (at days 0 and 14 after laser injury) and histological
      appearance. The lesions were assessed on RPE-choroidal flatmounts after CD31
      labeling and with confocal microscopy after perfusion with rhodamine-labeled
      concanavalin A (Con A). Apoptosis was quantified by TUNEL positivity and caspase
      activation. FasL mRNA and protein were highly expressed in the RPE of the
      transgenic mice before and after laser photocoagulation. In contrast, FasL was
      only weakly expressed in the RPE layer of WT C57BL/6J mice. While ruptures of
      Bruch's membrane and CNV formation were observed histologically two weeks after
      laser photocoagulation in transgenic as well as control eyes, the shape and size
      of CNV lesions were reduced in the transgenic mice. The area of leakage was
      decreased by 70% in FasL transgenic mice compared with WT mice (P<0.005). The
      number of TUNEL-positive cells was greater in FasL-overexpressing mice and
      correlated with the expression of activated caspases. Th expression of other
      antiangiogenic factors such as PEDF remained unchanged. The specific
      overexpression of FasL in RPE layer reduced CNV formation in our laser model. Our
      results strongly point to the FasL-Fas pathway as a potential therapeutic target
      in controlling pathological choroidal neovascularization.

PMID- 16807369
TI  - Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a
      new host defense mechanism.
AB  - Tat, the HIV transactivating protein, and matrix metalloproteinases (MMPs), a
      family of extracellular matrix (ECM) endopeptidases, have been implicated in the
      pathogenesis of HIV-associated dementia. However, the possibility that MMPs
      interact with viral proteins has remained unexplored. We therefore treated mixed
      human fetal neuronal cultures with recombinant Tat and select MMPs. Neurotoxicity
      was determined by measuring mitochondrial membrane potential and neuronal cell
      death. Previous studies have shown that Tat and MMP independently cause
      neurotoxicity. Surprisingly, we found the combination of Tat and MMP produced
      significant attenuation of neurotoxicity. To determine whether there was a
      physical interaction between Tat and MMP, we used protein electrophoresis and
      Western blot techniques, and found that MMP-1 can degrade Tat. This effect was
      blocked by MMP inhibitors. Furthermore, MMP-1 decreased Tat-mediated
      transactivation of the HIV long terminal repeat region, and this functionality
      was restored when MMP-1 activity was inhibited. These results suggest that the
      decrease in Tat-induced neurotoxicity and HIV transactivation is due to Tat's
      enzymatic cleavage by MMP-1. The direct interaction of human MMPs with viral
      proteins has now been demonstrated, with resultant modulation of Tat-mediated
      neurotoxicity and transactivation. This study elucidates a unique viral-host
      interaction that may serve as an innate host defense mechanism.

PMID- 16807370
TI  - Coding region paraoxonase polymorphisms dictate accentuated neuronal reactions in
      chronic, sub-threshold pesticide exposure.
AB  - Organophosphate pesticides (OPs), known inhibitors of acetylcholinesterase
      (AChE), are used extensively throughout the world. Recent studies have focused on
      the ACHE/PON1 locus as a determinant of inherited susceptibility to environmental
      OP exposure. To explore the relationship of the corresponding gene-environment
      interactions with brain activity, we integrated neurophysiologic,
      neuropsychological, biochemical, and genetic methods. Importantly, we found that
      subthreshold OP exposure leads to discernible physiological consequences that are
      significantly influenced by inherited factors. Cortical EEG analyses by LORETA
      revealed significantly decreased theta activity in the hippocampus,
      parahippocampal regions, and the cingulate cortex, as well as increased beta
      activity in the prefrontal cortex of exposed individuals-areas known to play a
      role in cholinergic-associated cognitive functions. Through neuropsychological
      testing, we identified an appreciable deficit in the visual recall in exposed
      individuals. Other neuropsychological tests revealed no significant differences
      between exposed and non-exposed individuals, attesting to the specificity of our
      findings. Biochemical analyses of blood samples revealed increases in paraoxonase
      and arylesterase activities and reduced serum acetylcholinesterase activity in
      chronically exposed individuals. Notably, specific paraoxonase genotypes were
      found to be associated with these exposure-related changes in blood enzyme
      activities and abnormal EEG patterns. Thus, gene-environment interactions
      involving the ACHE/PON1 locus may be causally involved in determining the
      physiological response to OP exposure.

PMID- 16807371
TI  - Activation of sPLA2-IIA and PGE2 production by high mobility group protein B1 in
      vascular smooth muscle cells sensitized by IL-1beta.
AB  - Lipid mediators such as prostaglandin E2 (PGE2) play a central role during
      atherogenesis as a consequence of inflammation. PGE2 is produced from
      phospholipids by a cascade of enzymatic reactions involving phospholipase A2
      (PLA2), cyclooxygenase (COX), and prostaglandin E synthase (PGES). It is released
      by several cell types, including vascular smooth muscle cells (VSMCs). Recent
      work has shown that the secretory PLA2-IIA (sPLA2-IIA), the most abundant isoform
      of secreted PLA2 in VSMCs, acts as a potent cytokine and activates VSMCs through
      a positive feedback loop. High mobility group protein 1 (HMGB1), also known as
      amphoterin, is a ubiquitous protein that plays various roles in the nucleus.
      HMGB1 is released by necrotic cells and by immune cells in response to various
      inflammatory mediators and acts as a potent proinflammatory cytokine. The present
      study investigates the role of HMGB1 in the activation of sPLA2-IIA expression
      and PGE2 production in VSMCs. Recombinant HMGB1 slightly activated the sPLA2-IIA,
      COX-2, and mPGES-1 genes but dramatically stimulated these genes in VSMCs that
      had been incubated with the proinflammatory cytokine IL-1beta for 24 h. This
      effect was accompanied by significantly increased PGE2 release. Induction of the
      three known receptors of HMGB1, namely RAGE, TLR-2, and TLR-4, by IL-1beta
      suggests that proinflammatory cytokines sensitize VSMCs to HMGB1. This provides
      new insights into the role of HMGB1 in VSMCs, suggesting it may be essential for
      the progression of atherosclerosis.

PMID- 16807373
TI  - Evidence of calcium-dependent pathway in the regulation of human beta1,3
      glucuronosyltransferase-1 (GlcAT-I) gene expression: a key enzyme in proteoglycan
      synthesis.
AB  - The importance of heparan- and chondroitin-sulfate proteoglycans in physiological
      and pathological processes led to the investigation of the regulation of beta1,3
      glucuronosyltransferase I (GlcAT-I), responsible for the completion of
      glycosaminoglycan-protein linkage tetrasaccharide, a key step prior to
      polymerization of chondroitin- and heparan-sulfate chains. We have cloned and
      functionally characterized GlcAT-I 5'-flanking regulatory region. Mutation
      analysis and electrophoretic mobility shift assays demonstrated the importance of
      Sp1 motif located at -65/-56 position in promoter activity. Furthermore, we found
      that elevation of intracellular calcium concentration by the calcium ionophore
      ionomycin stimulated GlcAT-I gene expression as well as glycosaminoglycan chain
      synthesis in HeLa cells. Bisanthracycline, an anti-Sp1 compound, inhibited GlcAT
      I basal promoter activity and suppressed ionomycin induction, suggesting the
      importance of Sp1 in calcium induction of GlcAT-I gene expression. Nuclear
      protein extracts from ionomycin-induced cells exhibited an increased DNA binding
      of Sp1 factor to the consensus sequence at position -65/-56. Signaling pathway
      analysis and MEK inhibition studies revealed the important role of p42/p44 MAPK
      in the stimulation of GlcAT-I promoter activity by ionomycin. The present study
      identifies, for the first time, GlcAT-I as a target of calcium-dependent
      signaling pathway and evidences the critical role of Sp1 transcription factor in
      the activation of GlcAT-I expression.

PMID- 16807372
TI  - Biglycan regulates the expression and sarcolemmal localization of dystrobrevin,
      syntrophin, and nNOS.
AB  - The dystrophin-associated protein complex (DAPC) provides a linkage between the
      cytoskeleton and the extracellular matrix (ECM) and is also a scaffold for a host
      of signaling molecules. The constituents of the DAPC must be targeted to the
      sarcolemma in order to properly function. Biglycan is an ECM molecule that
      associates with the DAPC. Here, we show that biglycan null mice exhibit a mild
      dystrophic phenotype and display a selective reduction in the localization of
      alpha-dystrobrevin-1 and -2, alpha- and beta1-syntrophin, and nNOS at the
      sarcolemma. Purified biglycan induces nNOS redistribution to the plasma membrane
      in cultured muscle cells. Biglycan protein injected into muscle becomes stably
      associated with the sarcolemma and ECM for at least 2 wk. This injected biglycan
      restores the sarcolemmal expression of alpha-dystrobrevin-1 and -2, and beta1-
      and beta2-syntrophin in biglycan null mice. We conclude that biglycan is
      important for the maintenance of muscle cell integrity and plays a direct role in
      regulating the expression and sarcolemmal localization of the intracellular
      signaling proteins dystrobrevin-1 and -2, alpha- and beta1-syntrophin and nNOS.

PMID- 16807374
TI  - Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice
      identifies novel markers for brain pericytes.
AB  - Normal blood microvessels are lined by pericytes, which contribute to microvessel
      development and stability through mechanisms that are poorly understood. Pericyte
      deficiency has been implicated in the pathogenesis of microvascular abnormalities
      associated with diabetes and tumors. However, the unambiguous identification of
      pericytes is still a problem because of cellular heterogeneity and few available
      molecular markers. Here we describe an approach to identify pericyte markers
      based on transcription profiling of pericyte-deficient brain microvessels
      isolated from platelet-derived growth factor (PDGF-B)-/- and PDGF beta receptor
      (PDGFRbeta)-/- mouse mutants. The approach was validated by the identification of
      known pericyte markers among the most down-regulated genes in PDGF-B-/- and
      PDGFRbeta-/- microvessels. Of candidates for novel pericyte markers, we selected
      ATP-sensitive potassium-channel Kir6.1 (also known as Kcnj8) and sulfonylurea
      receptor 2, (SUR2, also known as Abcc9), both part of the same channel complex,
      as well as delta homologue 1 (DLK1) for in situ hybridization, which demonstrated
      their specific expression in brain pericytes of mouse embryos. We also show that
      Kir6.1 is highly expressed in pericytes in brain but undetectable in pericytes in
      skin and heart. The three new brain pericyte markers are signaling molecules
      implicated in ion transport and intercellular signaling, potentially opening new
      windows on pericyte function in brain microvessels.

PMID- 16807375
TI  - Regulation of mouse hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde
      decarboxylase, a key enzyme in the tryptophan-nicotinamide adenine dinucleotide
      pathway, by hepatocyte nuclear factor 4alpha and peroxisome proliferator
      activated receptor alpha.
AB  - Nicotinamide adenine dinucleotide (NAD) plays a critical role in the maintenance
      of cellular energy homeostasis. alpha-Amino-beta-carboxymuconate-epsilon
      semialdehyde decarboxylase (ACMSD) is the key enzyme regulating de novo synthesis
      of NAD from l-tryptophan (Trp), designated the Trp-NAD pathway. Acmsd gene
      expression was found to be under the control of both hepatocyte nuclear factor
      4alpha (HNF4alpha) and peroxisome proliferator-activated receptor alpha
      (PPARalpha). Constitutive expression of ACMSD mRNA levels were governed by
      HNF4alpha and downregulated by activation of PPARalpha by the ligand Wy-14,643
      ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid]), as revealed by
      studies with hepatic HNF4alpha-null mice and PPARalpha-null mice, respectively.
      Transient transfection and electrophoretic mobility shift analyses showed an
      HNF4alpha binding site in the Acmsd gene promoter that directed transactivation
      of reporter gene constructs by HNF4alpha. The Acmsd promoter was not responsive
      to PPARalpha in transactivation assays. Wy-14,643 treatment decreased HNF4alpha
      protein levels in wild-type, but not PPARalpha-null, mouse livers, with no
      changes in HNF4alpha mRNA. These results show that Wy-14,643, through PPARalpha,
      post-transcriptionally down-regulates HNF4alpha protein levels, leading to
      reduced expression of the HNF4alpha target gene Acmsd.

PMID- 16807376
TI  - Endocrine regulation of gender-divergent mouse organic anion-transporting
      polypeptide (Oatp) expression.
AB  - Several examples of gender-divergent pharmacokinetics exist in humans and
      experimental animals, and one reason for these variations may be gender
      differences in transporter expression. Organic anion transporting polypeptides
      (Oatp) are transporters involved in hepatic and renal uptake of many organic
      compounds. In mouse livers, Oatp1a1 is male-predominant, whereas Oatp1a4 is
      female-predominant. However, in kidneys, Oatp1a1 and Oatp3a1 are both female
      predominant. The purpose of the present study was to determine whether sex
      hormones and/or growth hormone (GH) secretion patterns are responsible for the
      gender-specific Oatp expression in mice. Gonadectomized mice, GH-releasing
      hormone receptor-deficient little (lit/lit) mice, and hypophysectomized mice were
      used with replacement of sex hormones or GH in male or female secretion patterns.
      Androgens increased Oatp1a1 mRNA in liver and kidney, whereas male-pattern GH
      administration increased Oatp1a1 mRNA in livers but not in kidneys. Hepatic
      Oatp1a4 mRNA levels were decreased by both androgens and male-pattern GH
      administration. In kidneys, Oatp3a1 mRNA expression was only induced by androgen
      treatment. In conclusion, gender-divergent Oatp expression in liver is caused by
      male-pattern GH secretion pattern and androgens. In kidney, gender-divergent Oatp
      expression is exclusively caused by stimulation by androgens.

PMID- 16807377
TI  - Association of substance-use behaviours and their social-cognitive determinants
      in secondary school students.
AB  - In two samples of Flemish secondary school students, co-occurrence of different
      types of substance use was observed: smoking was associated with marijuana use in
      Sample 1 (n = 597) and alcohol consumption in Sample 2 (n = 403). It was
      investigated whether social-cognitive determinants of these behaviours were also
      associated. Low to medium correlations were observed. Confirmatory factor
      analyses showed that a model with general social-cognitive factors (across
      different substances) did not have adequate fit. Substance use was mainly
      associated with variables referring to the specific substance under
      consideration, with the exception of self-efficacy in buying and smoking
      cigarettes; this factor was linked not only to smoking but also to alcohol and
      marijuana use. Adolescents who regularly used two substances generally held
      positions on social-cognitive scales that were more unfavourable than those who
      only used one substance. In order to change determinants of use, substance
      specific cognitions and skills may be important targets.

PMID- 16807378
TI  - Fidelity of implementation in a treatment effectiveness trial of Reconnecting
      Youth.
AB  - In 'a treatment effectiveness trial', a program is evaluated in a real-world
      setting, with an emphasis on achieving high implementation fidelity. Through
      fidelity assessment, the link between program implementation and outcomes is
      systematically evaluated and ultimately leads to a greater understanding of
      program success or failure. This paper reports the results of an implementation
      fidelity study of the 'Reconnecting Youth' (RY) prevention program. The research
      questions were (i) was the program implemented with fidelity? and (ii) did better
      fidelity predict better outcomes? RY is an indicated drug abuse prevention
      program for high school students that seeks to 'reconnect' high-risk youth to
      school before they drop out. The results reported here were part of a randomized
      controlled effectiveness trial of the RY prevention program conducted in two
      urban school districts in which 15 teachers taught 41 RY classes. Overall,
      implementation fidelity was high with an average 90% of core lessons being
      taught. Unexpectedly, increased quality of implementation predicted increased
      alcohol use and anger. Adherence (teaching more of the curriculum) predicted
      increased marijuana use, while exposure (student attendance) significantly
      increased bonding to high-risk peers, alcohol use and anger.

PMID- 16807379
TI  - beta1-Integrins determine the dendritic morphology which enhances DC-SIGN
      mediated particle capture by dendritic cells.
AB  - The morphology of antigen-presenting dendritic cells (DCs) is characterized by
      the presence of numerous long dendrites. The formation of these processes is
      shown to require the interaction between the beta1-integrin (CD29) on the surface
      of the DCs and fibronectin in the extracellular matrix. This interaction occurs
      at focal contacts formed at the tips of dendrites, which contain high
      concentrations of the beta1-integrins, actin and the cytoskeletal proteins
      vinculin, paxillin and talin. Dendrites contain an extensive microtubule (MT)
      network, and are retracted in the presence of the MT inhibitor colchicine,
      suggesting that MTs are essential for dendrite stability. The dendritic
      morphology is shown to contribute directly to an enhanced ability to capture
      dendritic cell specific ICAM-3 grabbing nonintegrin (DC-SIGN)-coated beads. Time
      lapse photography demonstrates that dendrites are highly dynamic structures, with
      cells extending and retracting multiple dendrites in different directions over a
      3-h period. This motility increases the area scanned by an individual DC by over
      2-fold. The unusual combination of a dendritic morphology and high motility is
      likely to play a major role in the efficient function of DCs as sentinels of the
      immune system.

PMID- 16807380
TI  - Full-term development of rat after transfer of nuclei from two-cell stage
      embryos.
AB  - Cloning technology would allow targeted genetic alterations in the rat, a species
      which is yet unaccessible for such studies due to the lack of germline-competent
      embryonic stem cells. The present study was performed to examine the
      developmental ability of reconstructed rat embryos after transfer of nuclei from
      early preimplantation stages. We observed that single blastomeres from two-cell
      embryos and zygotes reconstructed by pronuclei exchange can develop in vitro
      until morula/blastocyst stage. When karyoplasts from blastomeres were used for
      the reconstruction of embryos, highest in vitro cleavage rates were obtained with
      nuclei in an early phase of the cell cycle transferred into enucleated
      preactivated oocytes or zygotes. However, further in vitro development of
      reconstructed embryos produced from blastomere nuclei was arrested at early
      cleavage stages under all conditions tested in this study. In contrast, immediate
      transfer to foster mothers of reconstructed embryos with nuclei from two-cell
      embryos at an early stage of the cell cycle in preactivated enucleated oocytes
      resulted in live newborn rats, with a general efficiency of 0.4%-2.2%. The
      genetic origin of the cloned offspring was verified by using donor nuclei from
      embryos of Black Hooded Wistar rats and transgenic rats carrying an ubiquitously
      expressed green fluorescent protein transgene. Thus, we report for the first time
      the production of live cloned rats using nuclei from two-cell embryos.

PMID- 16807381
TI  - SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid
      dehydrogenase type 2 gene in human endometrium.
AB  - The opposing actions of estrogen and progesterone during the menstrual cycle
      regulate the cyclical and predictable endometrial proliferation and
      differentiation that is required for implantation. Progesterone indirectly
      stimulates the expression of 17beta hydroxysteroid dehydrogenase type 2
      (HSD17B2), which catalyzes the conversion of biologically potent estradiol to
      weakly estrogenic estrone in the endometrial epithelium. We previously
      demonstrated upregulation of the HSD17B2 gene in human endometrial epithelial
      cells by factors secreted from endometrial stromal cells in response to
      progesterone. We investigated the underlying mechanism by which these stroma
      derived, progesterone-induced paracrine factors stimulate HSD17B2 expression.
      Here, we show that transcription factors SP1 and SP3 interact with specific
      motifs in HSD17B2 promoter to upregulate enzyme expression in human endometrial
      epithelial cell lines. Conditioned medium (CM) from progestin-treated stromal
      cells increased levels of SP1 and SP3 in endometrial epithelial cells and induced
      HSD17B2 mRNA expression. Mithramycin A, an inhibitor of SP1-DNA interaction,
      reduced epithelial HSD17B2 promoter activity in a dose-dependent manner. Serial
      deletion and site-directed mutants of the HSD17B2 promoter demonstrated that two
      overlapping SP1 motifs (nt -82/-65) are essential for induction of promoter
      activity by CM or overexpression of SP1/SP3. CM markedly enhanced, whereas anti
      SP1/SP3 antibodies inhibited, binding of nuclear proteins to this region of the
      HSD17B2 promoter. In vivo, we demonstrated a significant spatiotemporal
      association between epithelial SP1/SP3 and HSD17B2 levels in human endometrial
      biopsies. Taken together, these data suggest that HSD17B2 expression in
      endometrial epithelial cells, and, therefore, estrogen inactivation, is regulated
      by SP1 and SP3, which are downstream targets of progesterone-dependent paracrine
      signals originating from endometrial stromal cells.

PMID- 16807382
TI  - Sex steroids are involved in the regulation of gonadotropin-releasing hormone and
      dopamine D2 receptors in female tilapia pituitary.
AB  - Although molecular mechanisms underlying steroid effects on GnRH and dopamine
      receptors are well documented in mammals, little is known in fish. Herein, we
      describe the expression of pituitary GnRH and dopamine receptors relative to
      gonadotropin expression and release. We exposed female tilapia to graded doses of
      estradiol or 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) in vitro, and of
      estradiol in vivo, and determined mRNA levels of gnrhr1, gnrhr3, drd2, lhb, and
      fshb by real-time PCR. We also determined gonadotropin levels using specific
      ELISAs. Exposure to low doses of estradiol caused increased gnrhr3 mRNA levels in
      vivo and in vitro, probably related to positive feedback on FSH release.
      Increasing concentrations of estradiol resulted in increased drd2 mRNA levels in
      vivo and in vitro, inhibition of LH and FSH release, and inhibition of lhb mRNA
      levels in vivo, possibly related to negative feedback. At high doses of
      estradiol, FSH release increased in preparation for a new generation of
      follicles. Exposure to nanomolar doses of DHP resulted in increased drd2 mRNA
      levels, probably related to negative feedback on LH release. A decrease in drd2
      levels at the micromolar range of DHP (concomitant with increased gnrhr3 and fshb
      mRNA levels) may be related to the recruitment of a new generation of oocytes.
      Exposure to DHP also resulted in increased lhb mRNA levels toward final oocyte
      maturation. Salmon GnRH analog (sGnRHa) increased mRNA levels of gnrh1and gnrh3;
      when combined with DHP, sGnRHa synergistically increased expression of gnrh3
      only. These results emphasize the role of sex steroids on positive and negative
      feedbacks controlling the reproductive cycle.

PMID- 16807383
TI  - A growth-maturation system that enhances the meiotic and developmental competence
      of porcine oocytes isolated from small follicles.
AB  - In livestock, most of the follicles on the ovarian surface are small follicles. A
      procedure that supports the in vitro growth and maturation of these small
      follicle-derived oocytes may offer a new source of useable oocytes for both
      biotechnological and fundamental research purposes. The objective of the current
      study was to test the hypothesis that providing a more growth-supporting and less
      maturation-promoting environment during the first phase of small follicle-derived
      oocyte maturation may improve oocyte competence for meiosis and embryo
      development upon activation. In our small follicle-derived oocyte growth
      maturation system (SGM group), cumulus-oocyte complexes (COCs) from small
      follicles (1-3 mm) were first cultured in oocyte growth medium for 24 h, then in
      oocyte maturation medium for 20 h. As controls, COCs from small (SM group) and
      large (LM group) follicles were cultured using a conventional in vitro maturation
      (IVM) approach in which they were directly cultured in oocyte maturation medium.
      At 24 h of culture, the percentage of small follicle-derived oocytes that
      underwent germinal vesicle breakdown (GVBD) in the SGM group was comparable to
      that of large follicle-derived oocytes (LM group) but was significantly higher
      than that of the SM group (P < 0.05). At 44 h of culture, compared to 36% in the
      SM group, 55% of the SGM group oocytes reached metaphase II (MII; P < 0.05). In
      addition, the level of cyclin B in oocytes of the SGM group was comparable to
      that of oocytes from LM group and was significantly higher than that of oocytes
      from the SM group (P < 0.05). When activated and in vitro fertilized (IVF), 7.3
      and 9.0 times more parthenogenetic and IVF embryos developed to blastocyst stage
      in the SGM group than in the SM group (P < 0.05). The mRNA expression levels of
      three developmentally important genes--DNA-methyltransferase 1, Pou domain class
      5 transcription factor 1, and Fibroblast growth factor receptor 2--in embryos of
      the SGM group were comparable to those of embryos developed from the LM group,
      whereas they were significantly lower in those of the SM group (P < 0.05). Our
      data suggest that the oocyte growth-maturation system facilitates the final stage
      of oocyte growth and thus resulted in better oocyte nuclear, cytoplasmic
      maturation, and developmental competency compared with the conventional direct
      oocyte maturation system.

PMID- 16807384
TI  - Circadian clock gene expression in the ovary: Effects of luteinizing hormone.
AB  - A molecular device that measures time on a daily, or circadian, scale is a nearly
      ubiquitous feature of eukaryotic organisms. A core group of clock genes, whose
      coordinated function is required for this timekeeping, is expressed both in the
      central clock and within numerous peripheral organs. We examined expression of
      clock genes in the rat ovary. Transcripts for core oscillator elements (Arntl,
      Clock, Per1, Per2, and Cry1) were present in the ovary as indicated by
      quantitative real-time RT-PCR. Rhythmic expression patterns of Arntl and Per2
      transcripts and protein products were out of phase with respect to the central
      oscillator and in complete antiphase to each other. Expression of Arntl was
      significantly elevated after the LH surge on the day of proestrus. Finally, hCG
      treatment induced cyclic expression of both Arntl and Per2 gene products in
      hypophysectomized, immature rats primed with eCG. Collectively, these data
      suggest that the core underpinnings of the transcriptional/translational feedback
      loop that drives circadian rhythmicity is present in the rat ovary. Furthermore,
      the study identifies LH as a potential regulator of circadian clock gene rhythms
      in the ovary.

PMID- 16807385
TI  - Restoration of spermatogenesis and male fertility by transplantation of dispersed
      testicular cells in the chicken.
AB  - Transplantation of male germ cells into sterilized recipients has been widely
      used in mammals for conventional breeding and transgenesis purposes. This study
      presents a workable approach for germ cell transplantation between male chickens.
      Testicular cells from adult and prepubertal donors were dispersed and
      transplanted by injection directly into the testes of recipient males sterilized
      by repeated gamma irradiation. We describe the repopulation of the recipient
      seminiferous epithelium up to the production of heterologous sperm in about 50%
      of transplanted males. In comparison to males transplanted with testicular cell
      preparations from adult donors, in which the first ejaculates with sperm were
      recovered about 5 wk after transfer, a substantial interval (about 10 wk) was
      necessary to obtain ejaculates after the transfer of testicular cells from
      prepubertal donors. However, in both cases, recipient males produced ejaculates
      capable of fertilizing ova and producing progeny expressing donor genes.

PMID- 16807386
TI  - Combination therapy for exercise intolerance in COPD.

PMID- 16807387
TI  - COX-2: a link between airway inflammation and disordered chloride secretion in
      cystic fibrosis?

PMID- 16807389
TI  - Diagnosing CF: sweat, blood and years.

PMID- 16807388
TI  - When in doubt should we cut it out? The role of surgery in non-small cell lung
      cancer.

PMID- 16807390
TI  - The burden of lung disease.

PMID- 16807392
TI  - Alveolar haemorrhage in anti-glomerular basement membrane disease without
      detectable antibodies by conventional assays.
AB  - Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of
      disease attributable to circulating anti-GBM antibodies. While active anti-GBM
      disease in the absence of circulating anti-GBM antibodies has been described, it
      is considered rare with the use of current routinely available assays. We report
      four subjects with features consistent with active anti-GBM antibody disease
      without detectable antibodies by routinely available enzyme linked immunosorbent
      assay (ELISA) and immunoblot techniques. All were smokers who presented with
      diffuse alveolar haemorrhage, minimal renal involvement, and undetectable anti
      GBM antibodies. Seronegative anti-GBM disease with predominant pulmonary
      involvement may be more common than previously appreciated and should be part of
      the differential diagnosis for otherwise unexplained diffuse alveolar
      haemorrhage. Renal biopsy with immunofluorescent studies should be considered in
      the diagnostic evaluation of such subjects, including those with idiopathic
      pulmonary haemosiderosis.

PMID- 16807391
TI  - Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute
      respiratory distress syndrome (ARDS): paradox or paradigm?
AB  - Acute respiratory distress syndrome (ARDS), the most severe form of acute lung
      injury (ALI), remains a devastating condition with a high mortality. It is
      characterised by alveolar injury and increased pulmonary vascular permeability.
      Vascular endothelial cell growth factor (VEGF) was identified by its properties
      to increase permeability and act as a cellular growth factor, hence its potential
      for a key role in the pathogenesis of ALI/ARDS. This review describes the basic
      biology of VEGF and its receptors as an essential prerequisite to discussing the
      available and sometimes paradoxical published data, before considering a paradigm
      for the role of VEGF in the human lung.

PMID- 16807393
TI  - Etanercept in chronic severe asthma.

PMID- 16807394
TI  - High Pseudomonas aeruginosa acquisition rate in CF.

PMID- 16807395
TI  - TB screening and anti-TNFalpha treatment.

PMID- 16807396
TI  - Association between sibship size and allergic diseases in the Glasgow Alumni
      Study.

PMID- 16807397
TI  - Prehospital standardization of medical airway management: incidence and risk
      factors of difficult airway.
AB  - OBJECTIVES: The rate of difficult intubation in prehospital emergency medicine
      varies greatly among studies already published and depends on several factors.
      The authors' objective was to determine the rate of difficult intubations and to
      determine factors associated with prehospital difficult airways when a standard
      protocol for sedation and intubation was applied. METHODS: This 30-month
      clinical, observational, prospective study was performed in a suburb of Paris,
      France (Val de Marne, population 1,300,000) by a prehospital emergency medical
      unit. Airway management for patients who needed tracheal intubation was
      standardized. The pharmacological procedure recommended rapid sequence intubation
      for patients with spontaneous cardiac activity. In cases of difficult,
      laryngoscopy-assisted intubation, a predefined algorithm was proposed. The
      Intubation Difficulty Score (IDS) was calculated for all patients requiring
      tracheal intubation, and factors associated with difficult intubation, defined by
      IDS of >5, were identified by using multivariate statistical analysis. RESULTS:
      During the study period, 1,442 patients were included; 640 (44%) were in
      cardiorespiratory arrest, and 802 had a spontaneous cardiac activity. Deviation
      from the pharmacological and airway management procedures occurred in 1% of
      cases. When the predefined difficult airway management algorithm was followed,
      failure to intubate was encountered twice (0.1%). One hundred six (7.4%) patients
      had an IDS of >5, and 60 (4.1%) required first (n = 56) then second (n = 4)
      alternative techniques for tracheal intubation. Semirigid leaders allowed
      tracheal access in 93% of difficult-intubation patients. One patient required a
      prehospital cricothyroidotomy. Factors associated with difficult intubation were
      the following: a history of ear, nose, or throat neoplasia or surgery; obesity;
      facial trauma; the operator's status; and the operator's position. CONCLUSIONS:
      If prehospital medical airway management is standardized and performed by trained
      operators, failure to intubate is rare (0.1%), and the incidence of difficult
      tracheal intubation is 7.4%, independent of cardiorespiratory status.

PMID- 16807398
TI  - System complexity as a measure of safe capacity for the emergency department.
AB  - OBJECTIVES: System complexity is introduced as a new measure of system state for
      the emergency department (ED). In its original form, the measure quantifies the
      uncertainty of demands on system resources. For application in the ED, the
      measure is being modified to quantify both workload and uncertainty to produce a
      single integrated measure of system state. METHODS: Complexity is quantified
      using an information-theoretic or entropic approach developed in manufacturing
      and operations research. In its original form, complexity is calculated on the
      basis of four system parameters: 1) the number of resources (clinicians and
      processing entities such as radiology and laboratory systems), 2) the number of
      possible work states for each resource, 3) the probability that a resource is in
      a particular work state, and 4) the probability of queue changes (i.e., where a
      queue is defined by the number of patients or patient orders being managed by a
      resource) during a specified time period. RESULTS: An example is presented to
      demonstrate how complexity is calculated and interpreted for a simple system
      composed of three resources (i.e., emergency physicians) managing varying patient
      loads. The example shows that variation in physician work states and patient
      queues produces different scores of complexity for each physician. It also
      illustrates how complexity and workload differ. CONCLUSIONS: System complexity is
      a viable and technically feasible measurement for monitoring and managing surge
      capacity in the ED.

PMID- 16807399
TI  - Surge capacity associated with restrictions on nonurgent hospital utilization and
      expected admissions during an influenza pandemic: lessons from the Toronto severe
      acute respiratory syndrome outbreak.
AB  - BACKGROUND: Current influenza pandemic models predict a surge in influenza
      related hospitalizations in affected jurisdictions. One proposed strategy to
      increase hospital surge capacity is to restrict elective hospitalizations, yet
      the degree to which this measure would meet the anticipated is unknown.
      OBJECTIVES: To compare the reduction in hospitalizations resulting from
      widespread nonurgent hospital admission restrictions during the Toronto severe
      acute respiratory syndrome (SARS) outbreak with the expected increase in
      admissions resulting from an influenza pandemic in Toronto. METHODS: The authors
      compared the expected influenza-related hospitalizations in the first eight weeks
      of a mild, moderate, or severe pandemic with the actual reduction in the number
      of hospital admissions in Toronto, Ontario, during the first eight weeks of the
      SARS-related restrictions. RESULTS: Influenza modeling for Toronto predicts that
      there will be 4,819, 8,032, or 11,245 influenza-related admissions in the first
      eight weeks of a mild, moderate, or severe pandemic, respectively. In the first
      eight weeks of SARS-related hospital admission restrictions, there were 3,654
      fewer hospitalizations than expected in Toronto, representing a modest 12%
      decrease in the overall admission rate (a reduction of 1.40 admissions per 1,000
      population). Therefore, influenza-related admissions could exceed the reduction
      in admissions resulting from restricted hospital utilization by 1,165 to 7,591
      patient admissions, depending on pandemic severity, which corresponds to an
      excess of 0.44 to 2.91 influenza-related admissions per 1,000 population per
      eight weeks, and an increase of 4% to 25% in the overall number of admissions,
      when compared with nonpandemic conditions. CONCLUSIONS: Pandemic modeling for
      Toronto suggests that influenza-related admissions would exceed the reduction in
      hospitalizations seen during SARS-related nonurgent hospital admission
      restrictions, even in a mild pandemic. Sufficient surge capacity in a pandemic
      will likely require the implementation of other measures, including possibly
      stricter implementation of hospital utilization restrictions.

PMID- 16807400
TI  - Identification and functional characterization of a new human kidney-specific
      H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2.
AB  - A cDNA coding a new H+/organic cation antiporter, human kidney-specific multidrug
      and toxin extrusion 2 (hMATE2-K), has been isolated from the human kidney. The
      hMATE2-K cDNA had an open reading frame that encodes a 566-amino acid protein,
      which shows 94, 82, 52, and 52% identity with the hMATE2, hMATE2-B, hMATE1, and
      rat MATE1, respectively. Reverse transcriptase-PCR revealed that hMATE2-K mRNA
      but not hMATE2 was expressed predominantly in the kidney, and hMATE2-B was
      ubiquitously found in all tissues examined except the kidney. The
      immunohistochemical analyses revealed that the hMATE2-K as well as the hMATE1 was
      localized at the brush border membranes of the proximal tubules. HEK293 cells
      that were transiently transfected with the hMATE2-K cDNA but not hMATE2-B
      exhibited the H+ gradient-dependent antiport of tetraethylammonium (TEA).
      Transfection of hMATE2-B had no affect on the hMATE2-K-mediated transport of TEA.
      hMATE2-K also transported cimetidine, 1-methyl-4-phenylpyridinium (MPP),
      procainamide, metformin, and N1-methylnicotinamide. Kinetic analyses demonstrated
      that the Michaelis-Menten constants for the hMATE2-K-mediated transport of TEA,
      MPP, cimetidine, metformin, and procainamide were 0.83 mM, 93.5 microM, 0.37 mM,
      1.05 mM, and 4.10 mM, respectively. Ammonium chloride-induced intracellular
      acidification significantly stimulated the hMATE2-K-dependent transport of
      organic cations such as TEA, MPP, procainamide, metformin, N1-methylnicotinamide,
      creatinine, guanidine, quinidine, quinine, thiamine, and verapamil. These results
      indicate that hMATE2-K is a new human kidney-specific H+/organic cation
      antiporter that is responsible for the tubular secretion of cationic drugs across
      the brush border membranes.

PMID- 16807401
TI  - Late-onset manifestation of antenatal Bartter syndrome as a result of residual
      function of the mutated renal Na+-K+-2Cl- co-transporter.
AB  - Genetic defects of the Na+-K+-2Cl- (NKCC2) sodium potassium chloride co
      transporter result in severe, prenatal-onset renal salt wasting accompanied by
      polyhydramnios, prematurity, and life-threatening hypovolemia of the neonate
      (antenatal Bartter syndrome or hyperprostaglandin E syndrome). Herein are
      described two brothers who presented with hyperuricemia, mild metabolic
      alkalosis, low serum potassium levels, and bilateral medullary nephrocalcinosis
      at the ages of 13 and 15 yr. Impaired function of sodium chloride reabsorption
      along the thick ascending limb of Henle's loop was deduced from a reduced
      increase in diuresis and urinary chloride excretion upon application of
      furosemide. Molecular genetic analysis revealed that the brothers were compound
      heterozygotes for mutations in the SLC12A1 gene coding for the NKCC2 co
      transporter. Functional analysis of the mutated rat NKCC2 protein by tracer-flux
      assays after heterologous expression in Xenopus oocytes revealed significant
      residual transport activity of the NKCC2 p.F177Y mutant construct in contrast to
      no activity of the NKCC2-D918fs frameshift mutant construct. However,
      coexpression of the two mutants was not significantly different from that of
      NKCC2-F177Y alone or wild type. Membrane expression of NKCC2-F177Y as determined
      by luminometric surface quantification was not significantly different from wild
      type protein, pointing to an intrinsic partial transport defect caused by the
      p.F177Y mutation. The partial function of NKCC2-F177Y, which is not negatively
      affected by NKCC2-D918fs, therefore explains a mild and late-onset phenotype and
      for the first time establishes a mild phenotype-associated SLC12A1 gene mutation.

PMID- 16807402
TI  - Macula densa control of renin secretion and preglomerular resistance in mice with
      selective deletion of the B isoform of the Na,K,2Cl co-transporter.
AB  - Na,K,2Cl co-transporter (NKCC2), the primary NaCl uptake pathway in the thick
      ascending limb of Henle, is expressed in three different full-length splice
      variants, called NKCC2F, NKCC2A, and NKCC2B. These variants, derived by
      differential splicing of the variable exon 4, show a distinct distribution
      pattern along the loop of Henle, but the functional significance of this
      organization is unclear. By introduction of premature stop codons into exon 4B,
      specific for the B isoform, mice with an exclusive NKCC2B deficiency were
      generated. Relative expression levels and distribution patterns of NKCC2A and
      NKCC2F were not altered in the NKCC2B-deficient mice. NKCC2B-deficient mice did
      not display a salt-losing phenotype; basal plasma renin and aldosterone levels
      were not different from those of wild-type mice. Ambient urine osmolarities,
      however, were slightly but significantly reduced. Distal Cl concentration was
      significantly elevated and loop of Henle Cl absorption was reduced in
      microperfused superficial loops of Henle of NKCC2B-deficient mice. Because of the
      presence of NKCC2A in the macula densa, maximum tubuloglomerular feedback
      responses were normal, but tubuloglomerular feedback function curves were right
      shifted, indicating reduced sensitivity in the subnormal flow range. Plasma renin
      concentration in NKCC2B-deficient mice was reduced under conditions of salt
      loading compared with that in wild-type mice. This study shows the feasibility of
      generating mice with specific deletions of single splice variants. The mild
      phenotype of mice that are deficient in the B isoform of NKCC2 indicates a
      limited role for NKCC2B for overall salt retrieval. Nevertheless, the high
      affinity NKCC2B contributes to salt absorption and macula densa function in the
      low NaCl concentration range.

PMID- 16807403
TI  - Increased water intake decreases progression of polycystic kidney disease in the
      PCK rat.
AB  - Renal enlargement in polycystic kidney disease (PKD) is caused by the
      proliferation of mural epithelial cells and transepithelial fluid secretion into
      the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the
      proliferation of human PKD cells in vitro via cAMP-dependent activation of the B
      Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK
      activity is elevated in cells that line the cysts in animals with PKD, and AVP
      receptor antagonists reduce ERK activity and halt disease progression. For
      suppression of the effect of AVP physiologically, water intake was increased in
      PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism,
      and function was determined. The addition of 5% glucose in the drinking water
      increased fluid intake approximately 3.5-fold compared with rats that received
      tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP
      excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water
      intake was associated with reduced renal expression of AVP V2 receptors (41.0%),
      B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen
      positive renal cells (61.7%). High water intake reduced the kidney/body weight
      ratio 28.0% and improved renal function. Taken together, these data demonstrate
      that water intake that is sufficient to cause persistent water diuresis
      suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK
      rats. It is suggested that limiting serum AVP levels by increased water intake
      may be beneficial to some patients with PKD.

PMID- 16807404
TI  - Mechanisms for renal blood flow control early in diabetes as revealed by chronic
      flow measurement and transfer function analysis.
AB  - The purpose of this study was to establish the roles of the myogenic response and
      the TGF mechanism in renal blood flow (RBF) control at the very earliest stages
      of diabetes. Mean arterial pressure (MAP) and RBF were measured continuously, 18
      h/d, in uninephrectomized control and diabetic rats, and transfer function
      analysis was used to determine the dynamic autoregulatory efficiency of the renal
      vasculature. During the control period, MAP averaged 91 +/- 0.5 and 89 +/- 0.4
      mmHg, and RBF averaged 8.0 +/- 0.1 and 7.8 +/- 0.1 ml/min in the control and
      diabetic groups, respectively. Induction of diabetes with streptozotocin caused a
      marked and progressive increase in RBF in the diabetic rats, averaging 10 +/- 6%
      above control on day 1 of diabetes and 22 +/- 3 and 34 +/- 1% above control by
      the end of diabetes weeks 1 and 2. MAP increased approximately 9 mmHg during the
      2 wk in the diabetic rats, and renal vascular resistance decreased. Transfer
      function analysis revealed significant increases in gain to positive values over
      the frequency ranges of both the TGF and myogenic mechanisms, beginning on day 1
      of diabetes and continuing through day 14. These very rapid increases in RBF and
      transfer function gain suggest that autoregulation is impaired at the very onset
      of hyperglycemia in streptozotocin-induced type 1 diabetes and may play an
      important role in the increase in RBF and GFR in diabetes. Together with previous
      reports of decreases in chronically measured cardiac output and hindquarter blood
      flow, this suggests that there may be differential effects of diabetes on RBF
      versus nonrenal BF control.

PMID- 16807405
TI  - Chronic inhibition of mammalian target of rapamycin signaling downregulates
      insulin receptor substrates 1 and 2 and AKT activation: A crossroad between
      cancer and diabetes?
AB  - Overactivation of the mammalian target of rapamycin (mTOR) branch downstream of
      the phosphatidylinositol 3-kinase-AKT pathway critically modulates insulin and
      growth factor signaling by insulin receptor substrates (IRS). On the basis of in
      vitro studies, the mTOR inhibitor rapamycin has been reported to lead to enhanced
      activation of AKT by relieving this feedback inhibition on IRS function. In view
      of the critical role of AKT in insulin signaling and tumorigenesis, the in vivo
      expression and activation of this kinase and of IRS-1 and IRS-2 were explored in
      PBMC of 30 patients who were treated long term with rapamycin. A marked decrease
      of basal and insulin-stimulated AKT phosphorylation, which correlated with the
      increase of patients' insulin resistance, and a significant increase of IRS total
      protein expression, together with a lower (IRS-2) or absent (IRS-1) increase of
      insulin-induced tyrosine phosphorylation, were found. Therefore, contrary to the
      expectations, long-term exposure to rapamycin caused the impairment of IRS
      signaling and AKT activation, and this would help to explain the
      antiproliferative effect and the possible deterioration of glucose metabolism
      that are observed in rapamycin-treated patients. These findings may form a novel
      basis for improved understanding of the role of mTOR inhibition in human
      diseases, such as diabetes and cancer.

PMID- 16807406
TI  - Molecular mechanism for elevation of asymmetric dimethylarginine and its role for
      hypertension in chronic kidney disease.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide
      synthase. ADMA is generated by protein methyltransferase (PRMT) and is
      metabolized mainly by dimethylarginine dimethylaminohydrolase (DDAH). ADMA levels
      are reported to increase in patients with chronic kidney disease (CKD), thereby
      playing a role in the pathogenesis of accelerated atherosclerosis in this
      population. However, the precise mechanism underlying ADMA accumulation in these
      patients is not fully understood. This study investigated the molecular mechanism
      for the elevation of ADMA levels in CKD, using a rat remnant kidney model that
      represents progressive CKD. After male Sprague-Dawley rats underwent baseline
      measurement of BP and renal function, 5/6 subtotal nephrectomy (5/6Nx) and 4/6
      nephrectomy were performed. Plasma and urinary levels of ADMA and symmetric
      dimethylarginine, an inert isomer of ADMA, were measured by HPLC. Expression
      levels of PRMT genes and DDAH proteins were analyzed by semiquantitative reverse
      transcription-PCR and Western blotting, respectively. Plasma ADMA levels were
      elevated in the Nx groups in proportion to the degree of nephrectomy despite
      marked increases in renal clearance of ADMA. In contrast, renal clearance of
      symmetric dimethylarginine was decreased and its plasma levels were increased in
      the Nx groups. Furthermore, both liver and kidney gene expression of PRMT was
      increased, whereas DDAH protein expression was decreased in the 5/6Nx group.
      Plasma ADMA levels were correlated with systolic BP levels. Moreover, adenovirus
      mediated DDAH gene transfer into the 5/6Nx rats prevented the elevation of BP
      levels, which was associated with the reduction of plasma and urinary ADMA
      levels. The results presented here suggest that decreased DDAH levels as well as
      increased PRMT gene expression could cause the elevation of plasma ADMA levels,
      thereby eliciting hypertension in CKD. Substitution of DDAH protein or
      enhancement of its activity may become a novel therapeutic strategy for the
      treatment of hypertension-related vascular injury in CKD.

PMID- 16807407
TI  - Haplotype of signal transducer and activator of transcription 3 gene predicts
      cardiovascular disease in dialysis patients.
AB  - Signal transducer and activator of transcription 3 (STAT3) protein has been
      linked to cardiovascular disease (CVD) through multiple pathways in experimental
      and animal studies. STAT3 gene variation was examined as a predictor of incident
      CVD in a subcohort of 529 incident white dialysis patients. Fifteen single
      nucleotide polymorphisms of the STAT3 gene were genotyped. Haplotypes were
      estimated using software PHASE 2.1, and associations with first CVD event were
      tested using Cox proportional hazards analysis. Adjusted global tests of
      haplotype association with incident CVD and inflammation markers were performed
      using permutated P value in R-package Haplo.score. An a priori specified additive
      genetic model was assumed for haplotype analysis. Both genotypes (four single
      nucleotide polymorphisms with P < 0.001) and haplotypes (P = 0.002 overall) were
      associated with incident CVD. Two major haplotype blocks, blocks A and C, were
      identified. Compared with common haplotype A-1, A-3 was associated with a hazard
      ratio (HR) of 0.70 (95% confidence interval [CI] 0.51 to 0.94) for CVD events
      after adjustment for covariates including C-reactive protein (CRP) and
      interleukin 6. Compared with common haplotype C-1, C-3 was associated with an
      adjusted HR of 2.12 (95% CI 1.25 to 3.57) for CVD events. Associations were
      independent of inflammation markers, but IL-6 levels were 14% lower (geometric
      mean ratio 0.86; 95% CI 0.77 to 0.96) per copy of haplotype A-3 compared with
      haplotype A-1 in block A after adjustment for CRP and other risk factors (P =
      0.008). Variation in the STAT3 gene is associated with the risk for CVD among
      white dialysis patients independent of serum IL-6 and CRP levels.

PMID- 16807409
TI  - Images in clinical medicine. Hypothyroid-induced hyporeflexia.

PMID- 16807408
TI  - ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).
AB  - Mutation in the CHMP2B gene has been implicated in frontotemporal dementia. The
      authors screened CHMP2B in patients with ALS and several cohorts of control
      samples. They identified mutations (Q206H; I29V) in two patients with non-SOD1
      ALS. Neuropathology of the Q206H case showed lower motor neuron predominant
      disease with ubiquitylated inclusions in motor neurons. Antibodies to p62
      (sequestosome 1) showed novel oligodendroglial inclusions in the motor cortex.

PMID- 16807410
TI  - For sale: physicians' prescribing data.

PMID- 16807411
TI  - Incidentalomas--clinical correlation and translational science required.

PMID- 16807412
TI  - Identification and survival of carriers of mutations in DNA mismatch-repair genes
      in colon cancer.
AB  - BACKGROUND: The identification of mutations in germ-line DNA mismatch-repair
      genes at the time of diagnosis of colorectal cancer is important in the
      management of the disease. METHODS: Without preselection and regardless of family
      history, we recruited 870 patients under the age of 55 years soon after they
      received a diagnosis of colorectal cancer. We studied these patients for germ
      line mutations in the DNA mismatch-repair genes MLH1, MSH2, and MSH6 and
      developed a two-stage model by multivariate logistic regression for the
      prediction of the presence of mutations in these genes. Stage 1 of the model
      incorporated only clinical variables; stage 2 comprised analysis of the tumor by
      immunohistochemical staining and tests for microsatellite instability. The model
      was validated in an independent population of patients. We analyzed 2938 patient
      years of follow-up to determine whether genotype influenced survival. RESULTS:
      There were 38 mutations among the 870 participants (4 percent): 15 mutations in
      MLH1, 16 in MSH2, and 7 in MSH6. Carrier frequencies in men (6 percent) and women
      (3 percent) differed significantly (P<0.04). The addition of immunohistochemical
      analysis in stage 2 of the model had a sensitivity of 62 percent and a positive
      predictive value of 80 percent. There were 35 mutations in the validation series
      of 155 patients (23 percent): 19 mutations in MLH1, 13 in MSH2, and 3 in MSH6.
      The performance of the model was robust among a wide range of cutoff
      probabilities and was superior to that of the Bethesda and Amsterdam criteria for
      hereditary nonpolyposis colorectal cancer. Survival among carriers was not
      significantly different from that among noncarriers. CONCLUSIONS: We devised and
      validated a method of identifying patients with colorectal cancer who are
      carriers of mutations in DNA repair genes. Survival was similar among carriers
      and noncarriers.

PMID- 16807413
TI  - A controlled trial of homocysteine lowering and cognitive performance.
AB  - BACKGROUND: The results of observational studies suggest that plasma homocysteine
      concentrations are inversely related to cognitive function in older people. Our
      objective was to test the hypothesis that lowering the plasma homocysteine
      concentration improves cognitive function in healthy older people. METHODS: We
      conducted a two-year, double-blind, placebo-controlled, randomized clinical trial
      involving 276 healthy participants, 65 years of age or older, with plasma
      homocysteine concentrations of at least 13 micromol per liter. Homocysteine
      lowering treatment was a daily supplement containing folate (1000 microg) and
      vitamins B12 (500 microg) and B6 (10 mg). Tests of cognition were conducted at
      baseline and after one and two years of treatment. Treatment effects were
      adjusted for baseline values, sex, and education. RESULTS: On average, during the
      course of the study, the plasma homocysteine concentration was 4.36 micromol per
      liter (95 percent confidence interval, 3.81 to 4.91 micromol per liter) lower in
      the vitamin group than in the placebo group (P<0.001). Overall, there were no
      significant differences between the vitamin and placebo groups in the scores on
      tests of cognition. CONCLUSIONS: The results of this trial do not support the
      hypothesis that homocysteine lowering with B vitamins improves cognitive
      performance. (Australian Clinical Trials registry number, ACTR NO
      12605000030673.).

PMID- 16807414
TI  - N-acetylcysteine and contrast-induced nephropathy in primary angioplasty.
AB  - BACKGROUND: Patients with acute myocardial infarction undergoing primary
      angioplasty are at high risk for contrast-medium-induced nephropathy because of
      hemodynamic instability, the need for a high volume of contrast medium, and the
      lack of effective prophylaxis. We investigated the antioxidant N-acetylcysteine
      for the prevention of contrast-medium-induced nephropathy in patients undergoing
      primary angioplasty. METHODS: We randomly assigned 354 consecutive patients
      undergoing primary angioplasty to one of three groups: 116 patients were assigned
      to a standard dose of N-acetylcysteine (a 600-mg intravenous bolus before primary
      angioplasty and 600 mg orally twice daily for the 48 hours after angioplasty),
      119 patients to a double dose of N-acetylcysteine (a 1200-mg intravenous bolus
      and 1200 mg orally twice daily for the 48 hours after intervention), and 119
      patients to placebo. RESULTS: The serum creatinine concentration increased 25
      percent or more from baseline after primary angioplasty in 39 of the control
      patients (33 percent), 17 of the patients receiving standard-dose N
      acetylcysteine (15 percent), and 10 patients receiving high-dose N-acetylcysteine
      (8 percent, P<0.001). Overall in-hospital mortality was higher in patients with
      contrast-medium-induced nephropathy than in those without such nephropathy (26
      percent vs. 1 percent, P<0.001). Thirteen patients (11 percent) in the control
      group died, as did five (4 percent) in the standard-dose N-acetylcysteine group
      and three (3 percent) in the high-dose N-acetylcysteine group (P=0.02). The rate
      for the composite end point of death, acute renal failure requiring temporary
      renal-replacement therapy, or the need for mechanical ventilation was 21 (18
      percent), 8 (7 percent), and 6 (5 percent) in the three groups, respectively
      (P=0.002). CONCLUSIONS: Intravenous and oral N-acetylcysteine may prevent
      contrast-medium-induced nephropathy with a dose-dependent effect in patients
      treated with primary angioplasty and may improve hospital outcome.
      (ClinicalTrials.gov number, NCT00237614[ClinicalTrials.gov]).

PMID- 16807415
TI  - Effect of iodine intake on thyroid diseases in China.
AB  - BACKGROUND: Iodine is an essential component of thyroid hormones; either low or
      high intake may lead to thyroid disease. We observed an increase in the
      prevalence of overt hypothyroidism, subclinical hypothyroidism, and autoimmune
      thyroiditis with increasing iodine intake in China in cohorts from three regions
      with different levels of iodine intake: mildly deficient (median urinary iodine
      excretion, 84 microg per liter), more than adequate (median, 243 microg per
      liter), and excessive (median, 651 microg per liter). Participants enrolled in a
      baseline study in 1999, and during the five-year follow-up through 2004, we
      examined the effect of regional differences in iodine intake on the incidence of
      thyroid disease. METHODS: Of the 3761 unselected subjects who were enrolled at
      baseline, 3018 (80.2 percent) participated in this follow-up study. Levels of
      thyroid hormones and thyroid autoantibodies in serum, and iodine in urine, were
      measured and B-mode ultrasonography of the thyroid was performed at baseline and
      follow-up. RESULTS: Among subjects with mildly deficient iodine intake, those
      with more than adequate intake, and those with excessive intake, the cumulative
      incidence of overt hypothyroidism was 0.2 percent, 0.5 percent, and 0.3 percent,
      respectively; that of subclinical hypothyroidism, 0.2 percent, 2.6 percent, and
      2.9 percent, respectively; and that of autoimmune thyroiditis, 0.2 percent, 1.0
      percent, and 1.3 percent, respectively. Among subjects with euthyroidism and
      antithyroid antibodies at baseline, the five-year incidence of elevated serum
      thyrotropin levels was greater among those with more than adequate or excessive
      iodine intake than among those with mildly deficient iodine intake. A baseline
      serum thyrotropin level of 1.0 to 1.9 mIU per liter was associated with the
      lowest subsequent incidence of abnormal thyroid function. CONCLUSIONS: More than
      adequate or excessive iodine intake may lead to hypothyroidism and autoimmune
      thyroiditis.

PMID- 16807417
TI  - Images in clinical medicine. Disseminated central nervous system nocardiosis.

PMID- 16807416
TI  - Clinical practice. Early Lyme disease.

PMID- 16807418
TI  - Case records of the Massachusetts General Hospital. Case 20-2006. An 84-year-old
      man with staphylococcal bacteremia and renal failure.

PMID- 16807419
TI  - Decoding hereditary colorectal cancer.

PMID- 16807420
TI  - Vitamin B12, folic acid, and the prevention of dementia.

PMID- 16807421
TI  - Iodine nutrition--more is better.

PMID- 16807422
TI  - The new era of medical imaging--progress and pitfalls.

PMID- 16807423
TI  - Fondaparinux versus enoxaparin in acute coronary syndromes.

PMID- 16807424
TI  - Enoxaparin versus unfractionated heparin in ST-elevation myocardial infarction.

PMID- 16807425
TI  - The Canadian Medical Association Journal.

PMID- 16807426
TI  - Prevalence of monoclonal gammopathy of undetermined significance.

PMID- 16807427
TI  - Case 8-2006: a woman with Crohn's disease and altered mental status.

PMID- 16807428
TI  - 1,3-beta-D-glucan in patients receiving intravenous amoxicillin-clavulanic acid.

PMID- 16807429
TI  - Imipenem in patients with immediate hypersensitivity to penicillins.

PMID- 16807430
TI  - Evaluating the effectiveness of the Massachusetts workforce development system
      using no-shows as a nonexperimental comparison group.
AB  - This article examines the effect of the Massachusetts workforce development
      system on the earnings of disadvantaged adults using nonexperimental data from
      the late 1990s. The authors construct a comparison sample for program
      participants using individuals who apply for and are offered services yet do not
      participate in a training program. They present a series of difference-in
      difference estimates that make several alternative efforts to correct for
      selectivity bias, including econometric models that regression adjust for
      observable characteristics and fixed-effect models that adjust for time-invariant
      person effects. They also employ probabilistic matching techniques to more finely
      align the treatment and comparison samples. On average, program participants
      experienced 20% increases in annual earnings 1 year postintervention and 25%
      increases after 2 years. The authors uncover considerable heterogeneity in these
      effects, suggesting that the most difficult to serve and the most job ready
      benefit the least.

PMID- 16807431
TI  - Evaluation of curricula in higher education: challenges for evaluators.
AB  - Evaluation of teaching at universities is traditionally realized in terms of
      student ratings. Curriculum evaluation is rarely done in a systematic manner.
      More often, the emphasis is placed on a particular aspect, which is only of
      little help in terms of modifying education. A very prominent example is that of
      medical education. Here, evaluations of curricula primarily focus on new
      curricula by contrasting them to traditional ones. The article at hand deals with
      a different evaluation approach, in which five phases have to be considered and
      contrasting results to other teaching formats are not the main focus. In this
      article, the authors concentrate on the first phase (baseline evaluation) of the
      systematic evaluation of a medical curriculum. They describe several challenges
      of such an evaluation approach and illustrate the strategies used to overcome
      them. In addition, associated relevant empirical findings from this evaluation
      study are presented.

PMID- 16807432
TI  - How to begin a new topic in mathematics: does it matter to students' performance
      in mathematics?
AB  - The authors use Canadian data from the Third International Mathematics and
      Science Study to examine six instructional methods that mathematics teachers use
      to introduce new topics in mathematics on performance of eighth-grade students in
      six mathematical areas (mathematics as a whole, algebra, data analysis, fraction,
      geometry, and measurement). Results of multilevel analysis with students nested
      within schools show that the instructional methods of having the teacher explain
      the rules and definitions and looking at the textbook while the teacher talks
      about it had little instructional effects on student performance in any
      mathematical area. In contrast, the instructional method in which teachers try to
      solve an example related to the new topic was effective in promoting student
      performance across all mathematical areas.

PMID- 16807433
TI  - Towards a faith-based program theory: a reconceptualization of program theory.
AB  - A meta-program theory is proposed to overcome the limitations and improve the use
      of program theory as an approach to faith-based program evaluation. The
      essentials for understanding religious organizations, their various programs, and
      faith and spirituality are discussed to support a rationale for developing a
      faith-based program theory that captures the complex nature of religious program
      phenomena. Implications for public policy are examined. New concepts based on
      structural approach and four program theories are formulated for program
      analysis. Several theoretical concepts for faith-based program evaluation to
      guide methods for describing patterns that reflect the religious beliefs and
      values are suggested.

PMID- 16807434
TI  - The imprecise science of evaluating scholarly performance: utilizing broad
      quality categories for an assessment of business and management journals.
AB  - In a growing number of countries, government-appointed assessment panels develop
      ranks on the basis of the quality of scholarly outputs to apportion budgets in
      recognition of evaluated performance and to justify public funds for future R&D
      activities. When business and management journals are being grouped in broad
      quality categories, a recent study has noted that this procedure was placing the
      same journals in essentially the same categories. Drawing on journal quality
      categorizations by several German- and English-speaking business departments and
      academic associations, the author performs nonparametric tests and correlations
      to analyze whether this claim can be substantiated. In particular, he examines
      the ability of broad quality categorizations to add value to governmental,
      administrative, and academic decision making by withstanding the criticism
      traditionally levied at research quality assessments.

PMID- 16807435
TI  - Pemetrexed and malignant pleural mesothelioma.
AB  - Malignant Pleural Mesothelioma (MPM) continues to be a challenging problem;
      because few patients may be treated with radical surgery and conventional
      chemotherapy have achieved very dismal results. Pemetrexed is a new drug with
      multitarget antifolate activity which seems to be particularly active in many
      solid tumors and also in MPM. The principal clinical experiences of pemetrexed
      alone or in combination with other compounds, chiefly platinum and its
      derivative, are reported. The Italian study on 1114 cases of MPM treated over 30
      months is discussed and the definitive results will be available after a complete
      external review of all responsive patients.

PMID- 16807436
TI  - Challenges in the treatment of bladder cancer.
AB  - Seventy to eighty percent of patients with newly-diagnosed bladder cancer will
      present with superficial tumors (Ta, Tis or T(1)). There is, however, a continuum
      between superficial and muscle-invasive cancer, with the advanced cases usually
      associated with less-differentiated histology and aneuploidy. Common sites of
      metastasis include regional lymph nodes, bone, lung, skin and liver. From the low
      cure rates achieved with radical cystectomy, there is strong evidence that
      bladder cancer, from the outset, is a systemic disease. The limitations of local
      treatment are well-documented: a local control rate of 30% with radiation
      treatment, and 50-70% with radical cystectomy; and no improvement in surgical
      cure was seen with the use of preoperative radiation. Over the past 30 years,
      since the initial reports of the effectiveness of cisplatin in the treatment of
      advanced bladder cancer, there has been a steady flow of chemotherapeutic agents,
      singly and in combination, shown to be effective in the treatment of this tumor.
      While response rates and CR rates have increased with the use of combination
      chemotherapy, this has not translated into survival in advanced disease of
      greater than 16 months. While the search for more effective agents and
      combinations continues, attention has also been given to the roles of neoadjuvant
      and adjuvant chemotherapy in an effort to improve the cure rate achieved with
      surgery alone. Although radical cystectomy, with continent diversion or
      neobladder construction in selected cases remains the standard of care in the
      United States for patients with muscle-invasive bladder cancer, several groups
      have explored therapeutic strategies that aim at bladder preservation. Early
      approaches with the goal of bladder preservation consisted of radiation treatment
      as monotherapy (largely abandoned) or aggressive TURBT for smaller tumors. Over
      the past 20 years, the Massachusetts General Hospital (MGH) and the Radiation
      Therapy Oncology Group (RTOG) have studied patients with muscle-invading bladder
      cancer utilizing tri-modality treatment: a visibly complete transurethral
      resection followed by radiation with concurrent radiosensitizing chemotherapy
      and, subsequently, adjuvant chemotherapy. Thus, chemotherapy has been used in two
      phases of treatment (1) as radiosensitizers, given concurrently with radiation
      treatment and (2) as adjuvant treatment, recognizing that survival will only be
      improved by the successful treatment of micrometastases. Based on preliminary
      information from reports of the effectiveness of gemcitabine/cisplatin in
      advanced disease, that combination was chosen as the adjuvant regimen in one of
      our earlier protocols, recently completed and reported. Our current protocol
      utilizes the Bellmunt regimen as our adjuvant program with the highest RR in
      advanced disease. This study is ongoing, with early reports of tolerance of the
      three-drug regimen encouraging. The treatment options for muscularis propria
      invasive bladder tumors can broadly be divided into those that spare the bladder
      and those that involve removing it. In the United States, radical cystectomy with
      pelvic lymph node dissection is the standard method used to treat patients with
      this tumor.

PMID- 16807437
TI  - Gemcitabine in the treatment of advanced transitional cell carcinoma of the
      urothelium.
AB  - M-VAC (cisplatin, methotrexate, adriamycin, vinblastine) combination chemotherapy
      has been for long time the standard of care in fit patient with advanced
      urothelial tumors. Gemcitabine/cisplatin with similar results and an improved
      toxicity profile has proved to be a new standard alternative. Whether or not we
      can improve survival with newer triplet regimens will depend upon the results of
      ongoing phase III trials. In addition to the new active drug combinations and
      targeted therapies, new approaches are emerging for treatment. Chemotherapy
      optimization using molecular markers predicting chemosensitivity are being
      applied. There is an obvious need to incorporate in clinical trials a systematic
      translational approach to explain both our successes and our failures.

PMID- 16807439
TI  - Actual experience and future development of gemcitabine in superficial bladder
      cancer.
AB  - Gemcitabine has a molecular weight of 299 D, lower than that of commonly-used
      intravesical chemotherapeutic agents such as mitomycin C (389 D) and doxorubicin
      (589 D). This may enable gemcitabine to penetrate the bladder mucosa with
      beneficial effects in the treatment of early invasive bladder cancer (T1
      disease). At the same time the molecular weight is high enough to prevent
      significant systemic absorption in an intact bladder. Based on the results of
      phase I studies, it appears that the 2000 mg dose of gemcitabine in 50/100 ml
      normal saline when administered intravesically for up to 2 h once a week for 6
      weeks has unremarkable systemic and local side effects and therefore should be
      considered the most convenient schedule. The currently available phase II studies
      have assessed the activity of intravesical gemcitabine on a marker lesion in
      intermediate risk superficial bladder cancers (SBC), showing complete responses
      in up to 56% of cases. Few attempts have been made to test the activity of
      intravesical gemcitabine in high risk SBC achieving unexpected complete responses
      in BCG refractory CIS. Gemcitabine seems to have fulfilled the requirements to be
      a promising new candidate for standard intravesical therapy in SBC so far.
      Further phase II trials exploring the activity of gemcitabine on highly-recurrent
      intermediate risk or high risk SBC would provide additional information to
      foresee its efficacy in clinical practice and thus constitute the framework for
      large comparative phase III trials.

PMID- 16807438
TI  - Long-term survival results of a randomized trial comparing gemcitabine/cisplatin
      and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally
      advanced and metastatic bladder cancer.
AB  - PURPOSE: To compare long-term survival in patients with locally advanced and
      metastatic transitional cell carcinoma (TCC) of the urothelium treated with
      gemcitabine plus cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin
      (MVAC). PATIENTS AND METHODS: Efficacy data from a large randomized phase III
      study of GC versus MVAC were updated. Time-to-event analyses were performed on
      the observed distributions of overall survival time and progression-free
      survival. RESULTS: Four hundred and five patients were randomized, 203 to the GC
      arm and 202 to the MVAC arm. At the time of this analysis, 347 patients have died
      (GC 176, MVAC 171). Overall survival was similar in both arms (HR 1.09; 95%
      confidence interval [CI] 0.88-1.34, P = 0.66) with a median survival of 14.0
      months (95% CI 12.3-15.5 months) in the GC, and 15.2 months (95% CI 13.2-17.3
      months) in the MVAC arm. The median progression-free survival was 7.7 months with
      GC (95% CI 6.8-8.8) and 8.3 months with MVAC (95% CI 7.3-9.7) with a HR of 1.09
      (95% CI 0.89-1.34). Significant prognostic factors favoring overall survival
      included performance status (>70), TNM staging (M0 vs. M1), low/normal alkaline
      phosphatase expression, number of sites of disease <3, and the absence of
      visceral metastasis. By adjusting for these prognostic factors, the HR was 0.99
      for overall survival and 1.01 for progression-free survival. CONCLUSIONS: Long
      term overall and progression-free survival following treatment with GC or MVAC
      are similar. These results strengthen the role of GC as a standard of care in
      patients with locally advanced and metastatic transitional-cell carcinoma (TCC).

PMID- 16807440
TI  - Adjuvant chemotherapy of bladder cancer.
AB  - BACKGROUND: Bladder cancer is one of the most common genitourinary cancer. 1/3 of
      patients presents with invasive disease. Radical cystectomy is the standard
      treatment for patients with muscle invasive disease: although local treatment can
      be curative, about 50% of patients will develop distant metastases. Optimal
      treatment for high risk patients includes local and perioperative systemic
      therapy (adjuvant or neoadjuvant chemotherapy). PATIENTS AND METHODS: We
      performed a review of clinical trials and metanalysis of adjuvant treatment for
      muscle-invasive bladder cancer. RESULTS: Data from single published trials of
      adjuvant chemotherapy (CT) are not univocal, and several methodological problems
      were found. A recent meta-analysis of individual patient data (IPD) from all
      eligible published and unpublished trials, found that adjuvant chemotherapy
      administration provides a significant survival and disease free survival
      advantage. Two large, multi-center, randomized trials are on-going to clarify the
      role of post-operative CT. CONCLUSIONS: A trend in favour of adjuvant
      chemotherapy comes out from some of the trials reviewed by us and by the
      metanalysis performed by the ABC collaborative group. However it is not clear yet
      which patients might derive the maximum benefit from such an approach and which
      ones might be safety candidate to deferred treatment, on relapse. The incoming
      results of the EORTC trial and of the Italian trial which are currently comparing
      the value of early vs. deferred treatment of patients at higher risk of relapse
      will probably provide an adequate answer to this question. Outside clinical
      trials, the potential benefit of adjuvant chemotherapy should be appropriately
      weighted versus the putative hazards and decision making appropriately tailored
      in the individual patients according to the aggressiveness of his/her disease and
      the presence of comorbidities.

PMID- 16807441
TI  - Pharmacogenomics and gemcitabine.
AB  - Approximately half of lung cancer patients present with metastases, and a large
      proportion will develop recurrent disease, with median survival to cisplatin
      based chemotherapy of 11 months. No predictive factor of response to cisplatin
      based chemotherapy is yet available in clinical practice. The nucleotide excision
      repair system plays a major role in repairing a variety of distorting lesions,
      notably platinum-induced DNA adducts. ERCC1 is a leading gene in repairing
      cisplatin DNA damage. We carried out three different studies examining
      individually the role of ERCC1, RRM1, and then both, mRNA expression in paraffin
      embedded pretreatment bronchial biopsies from gemcitabine/cisplatin-treated
      advanced non-small-cell lung cancer (NSCLC) patients. Median survival was
      significantly prolonged in patients with low levels of ERCC1 or RRM1. BRCA1 is
      involved in homologous recombination repair, and we observed that low levels of
      BRCA1 mRNA significantly increased survival in gemcitabine/cisplatin-treated
      patients. Our observations lead us to recommend that tumors be regularly assessed
      for ERCC1 and BRCA1 mRNA expression in order to customize gemcitabine/cisplatin
      treatment.

PMID- 16807442
TI  - A phase II study of gemcitabine and immunotherapy in renal cancer: preliminary
      results and review of the literature.

PMID- 16807443
TI  - Challenges in the treatment of gastrointestinal tumours.
AB  - In the last 20 years there have been many breakthroughs in the treatment of
      gastrointestinal tumours. In this review we have considered the three most
      important subgroups of gastrointestinal tumours (colorectal, gastric and
      pancreatic cancer), focusing on the state-of-the-art treatments.

PMID- 16807444
TI  - Pharmacokinetic evaluation of gemcitabine and 2',2'-difluorodeoxycytidine-5'
      triphosphate after prolonged infusion in patients affected by different solid
      tumors.
AB  - BACKGROUND: The study determined pharmacokinetic parameters, toxicity profile and
      preliminary clinical activity of gemcitabine administered i.v. at different
      infusion rates in patients with a range of solid tumors. PATIENTS AND METHODS:
      Twenty patients were enrolled for both pharmacokinetic and clinical studies.
      Gemcitabine 300 mg/m(2) was administered during 1 h, 2 h or 3 h, and as a
      conventional dose of 1000 mg/m(2) during 30 min infusion. Administration was on
      days 1, 8 and 15 every 4 weeks. RESULTS: Patients were randomly assigned to one
      of the four arms. After 30 min infusion of 1000 mg/m(2) gemcitabine the plasma
      concentration remained above the saturation level of 10-20 microM, whereas after
      1, 2 or 3 h infusion 300 mg/m(2) gemcitabine it remained below the saturation
      level for most of the time (being in the range 2.5-10 microM). Gemcitabine
      triphosphate was determined in the four arms in white blood cells; for infusion
      times from 0.5 to 3 h there was a progressive enhancement of gemcitabine
      triphosphate levels. In all evaluable patients the toxicity was mild,
      myelosuppression being the main toxicity. No grade 3 or 4 toxicities occurred.
      Clinical response was similar in patients receiving 300 mg/m(2) gemcitabine in 2
      and 3 h and in the 1000 mg/m(2) arm. CONCLUSIONS: 300 mg/m(2) gemcitabine during
      3 h infusion produced the highest accumulation of gemcitabine triphosphate. Thus,
      to achieve the highest possible gemcitabine triphosphate level, prolonged
      infusion time would appear to be more important than a high dose administered as
      a short infusion. However, there was no substantial difference in toxicity or
      antitumoral activity in the all different patient groups.

PMID- 16807445
TI  - New target therapies in advanced pancreatic cancer.
AB  - The recent elucidation both of the mechanisms involved in pancreatic cancer
      carcinogenesis and the related molecular events, has led to several distinct
      therapeutic advances, including many novel target agents, such as monoclonal
      antibodies against EGFR, EGFR-tyrosine kinase inhibitors, monoclonal antibody
      against VEGF, farnesyl transferase inhibitors, matrix metalloproteinase
      inhibitors, COX 2 inhibitors, and the development of gene therapy to target
      pancreatic cancer. This review highlights recent findings in the treatment of
      pancreatic cancer by using these novel therapeutic approaches.

PMID- 16807446
TI  - Gemcitabine and liposomal doxorubicin in biliary and hepatic carcinoma (HCC)
      chemotherapy: preliminary results and review of the literature.
AB  - BACKGROUND: Advanced biliary tract cancers have a poor prognosis. Gemcitabine (G)
      as a single agent or in combination represents an active treatment option.
      Systemic chemotherapy in hepatocellular carcinoma represents a palliative
      treatment. Gemcitabine in combination with Liposomal Doxorubicin (LD) may
      represent an active treatment option. PATIENTS AND METHODS: Clinical trials for
      biliary and hepatic carcinoma have been reviewed. RESULTS: We obtained RC (1 pt),
      RP (4 pts), SD (8 pts) and seven pts had PD (RR 25% and SD 40%). Our chemotherapy
      regimen was Gemcitabine 1000 mg/m(2) d 1 and 8, Liposomal Doxorubicin 30 mg d 1,
      q 28. Patients were 21 (17 M), aged 44 to 78 (median 63 yrs). Only in 8 pts we
      observed G 3-4 haematological toxicity, thrombocytopenia and neutropenia (7 G3, 1
      G4).

PMID- 16807447
TI  - Primary systemic therapy in operable breast cancer: clinical data and biological
      fall-out.
AB  - Primary systemic chemotherapy (PST) was first used in early 1970s for the
      treatment of locally advanced breast cancer; in this setting primary chemotherapy
      was administered to allow for radical surgery and the objective response rates
      were high with a substantial proportion of patients amenable to surgery. On the
      basis of this activity, PST was subsequently used to treat operable locally
      advanced or large primary tumors to increase the rate of conservative surgery.
      First generation clinical trials demonstrated that breast conservation rates were
      improved, that a proportion of patients experienced a complete pathologic
      response and that response to PST was a good predictor of long term outcome.
      Second generation of clinical trials were designed to compare PST to
      postoperative adjuvant chemotherapy: here again the rate of conservative surgery
      was significantly improved and the pathologic response rate demonstrated its
      prognostic value, however no progression free or survival improvement was
      obtained in comparison with postoperative treatments. Another interesting
      observation from these trials was that some tumor parameters (histology, grade,
      hormone receptor status) can predict the likelihood of achieving a pathologic
      complete response. On the basis of these data, PST can now be considered the
      standard of care for locally advanced disease, an reasonable option in case of
      large primary breast tumors not eligible for conservative surgery and an
      acceptable alternative for all the patients who are candidate to adjuvant
      treatment. It however clear that PST represents an excellent in vivo model to
      test new regimens, to evaluate biomarkers with predictive value and to evaluate
      the treatment induced modifications in tumor biology. Availability of new
      technologies able to measure the expression of thousands of genes and of new
      molecularly directed drugs will increase further the interest in this treatment
      strategy.

PMID- 16807448
TI  - First line chemotherapy of metastatic breast cancer.
AB  - In the last 20-30 years the approach to metastatic breast cancer by chemotherapy
      has been largely studied. Anthracyclines, taxanes and, more recently,
      capecitabine and gemcitabine represent the breakthrough of treatment. In the next
      future the combination of chemotherapy and target therapy will be considered more
      frequently.

PMID- 16807449
TI  - Gemcitabine: monochemotherapy of breast cancer.
AB  - BACKGROUND: Gemcitabine is a nucleoside analogue with proven activity in advanced
      and metastatic breast cancer. Its action is associated with a favourable toxicity
      profile which is mainly hematological. Its unique mechanism of action along with
      not overlapping toxicity is particularly useful both in combination treatment
      with other active drugs and a sequential therapy in the palliative setting.
      DESIGN: Phase II studies of gemcitabine performed over the last decade were
      reviewed. RESULTS AND CONCLUSIONS: Despite some conflicting results in some
      trials, gemcitabine confirmed to be a useful drug to treat this condition.

PMID- 16807450
TI  - In vitro studies on gemcitabine combinations with other antiblastics.
AB  - The use of gemcitabine in combination with chemotherapeutic agents, including
      cisplatin, pemetrexed and taxanes, is characterized by the enhancement of their
      anticancer activity. The analysis of the underlying pharmacodynamics has revealed
      that modulation of nucleotide pools, drug metabolism, and cellular DNA repair
      capability are the most common factors to explain the additive to synergistic
      interaction between gemcitabine and anticancer agents in several human cancers in
      vitro and in vivo.

PMID- 16807451
TI  - Gemcitabine and taxanes in metastatic breast cancer.

PMID- 16807452
TI  - Biological agents and gemcitabine in the treatment of breast cancer.

PMID- 16807453
TI  - Challenges for chemotherapy in ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is treated with surgery followed by combination
      chemotherapy with paclitaxel plus carboplatin. In an effort to improve outcomes,
      clinical trials are evaluating the following strategies: maintenance therapy;
      intraperitoneal drug administration; new combinations; novel cytotoxics;
      combination chemotherapy for recurrent disease; and molecular-targeted therapies.
      PATIENTS AND METHODS: Clinical trials evaluating the above strategies are being
      performed in ovarian cancer in patients with: (1) previously untreated advanced
      ovarian cancer; (2) platinum-sensitive recurrent disease; and (3) platinum
      resistant recurrent disease. RESULTS: Combination chemotherapy regimens are
      superior to single-agent therapy in recurrent ovarian cancer. Molecular-targeted
      therapy has produced objective responses in previously treated patients.
      Maintenance therapy of any type has not been shown to prolong survival.
      Intraperitoneal therapy has resulted in improved survival with considerable
      toxicity in patients with small-volume stage III disease. CONCLUSIONS: Numerous
      novel clinical strategies are being evaluated in ovarian cancers that have the
      potential to improve outcomes compared to standard therapy.

PMID- 16807454
TI  - Role of gemcitabine in ovarian cancer treatment.
AB  - Newer agents and combinations are needed in order to improve current results in
      ovarian cancer treatment. Gemcitabine is a novel agent that has shown promising
      activity as a single agent in the treatment of platinum-resistant ovarian cancer
      and a favorable toxicity profile. Because of its clinical and preclinical
      synergism with platinum analogues, Gemcitabine has been combined with Carboplatin
      as a convincing approach in the treatment of platinum-sensitive recurrent ovarian
      cancer patients. Further combination of Gemcitabine and other agents, including
      paclitaxel, are also feasible and have been actively studied in order to
      establish the role of Gemcitabine in the management of treated and untreated
      ovarian cancer patients.

PMID- 16807455
TI  - Gemcitabine and anthracyclines in platinum-resistant ovarian cancer.
AB  - BACKGROUND: Most of the patients with advanced ovarian cancer will recur after
      first-line platinum-based chemotherapy and need additional treatment. Gemcitabine
      (G) and Anthracyclines are active in this setting and their combination has shown
      synergistic antiproliferative activity in vitro, due to different mechanisms of
      action and non-overlapping toxicities. PATIENTS AND METHODS: In 2002 we began a
      phase II study with G 1000 mg/m(2) (day 1,8) combined to Epirubicin (E) 60
      mg/m(2) (day 1), every 3 weeks for 6 cycles, in Platinum resistant/refractory
      ovarian carcinoma patients. RESULTS: Among 30 patients enrolled so far (27
      evaluable), receiving 149 cycles (median 6), 1 complete and 12 partial responses
      (48%), 9 stabilizations (33%) and 5 progressions (18%) were observed, with a good
      correlation with serological responses. Median time to progression was 8 months,
      while median time to response was 10 weeks and median duration 8 months. Grade 3
      4 toxicities consisted of neutropenia (58%), thrombocytopenia (3%), anemia (10%),
      liver toxicity (13%), and mucositis (7%). Eight patients (27%) received G-CSF and
      3 (10%) blood transfusions. No febrile neutropenia nor cardiotoxicity were
      observed. CONCLUSIONS: Although our results are preliminary, G/E combination
      appears particularly effective and safe in these platinum resistant/refractory
      patients.

PMID- 16807456
TI  - Multimodal approach to ovarian cancer.

PMID- 16807457
TI  - In vitro basis for schedule-dependent interaction between gemcitabine and
      topoisomerase-targeted drugs in the treatment of colorectal cancer.
AB  - BACKGROUND: While combination of gemcitabine with anti-topoisomerase poisons is
      routinely used in oncology, little is known on the biological interactions
      between these drugs. DESIGN: To understand the cellular basis for this
      association, we hypothesized an interaction of the two agents at the
      topoisomerase level. A real-time RT-PCR method was designed to quantify
      topoisomerase expression after treatment with gemcitabine (GEM) in two human
      colon adenocarcinoma cell lines. Efficacy of drugs as single agents and in
      combination was analyzed on the basis of their cytotoxic effects. RESULTS: We
      showed that a) gemcitabine induces expression of all major eukaryotic
      topoisomerases (I, II alpha and beta) at definite times after drug
      administration; b) cytotoxicity was more relevant when cells were treated with
      GEM and the topoisomerase poison within a short period of time. In particular
      synergistic effects were found when the anti-topoisomerase II agent was given 3 h
      after gemcitabine or when the anti-topoisomerase I drug was delivered 3 h before
      or after the antimetabolite. CONCLUSIONS: These findings help explaining the
      effectiveness of the combined therapy GEM/topoisomerase poisons and suggest a
      drug administration protocol for clinical treatment.

PMID- 16807458
TI  - Topoisomerase I, II alpha and II beta mRNA expression in peripheral blood
      mononuclear cells of patients with solid tumor: preliminary results.
AB  - BACKGROUND: The pyrimidine antimetabolite Gemcitabine (G) (2',2'
      difluorodeoxycytidine) is used against several malignancies G exerts its
      antitumour effect mainly by incorporation of its triphosphate metabolite (dFdCTP)
      into DNA. Subsequently, DNA polymerase adds one additional deoxynucleotide and
      DNA synthesis is interrupted. The nuclear enzymes topoisomerase I and II (TPs)
      are critical for DNA function and cell survival; they control, maintain and
      modify DNA topology during both replication and translation of genetic materials.
      These enzymes induce cuts in one or both strands of DNA, allowing strands to pass
      through the nick and then rejoining the nicked strand of DNA. Anti-topoisomerase
      (TPs-inhibitors) drugs exist and are largely used in chemotherapy, however, most
      often blindly of the cancer TPs status. AIM: To understand the best association
      between G and TPs-inhibitors, we studied: (a) Topoisomerases I, II alpha and II
      beta mRNA expression in Peripheral Mononuclear Blood Cells (PBMCs) of patients
      with solid tumor, after 1, 2, 3, 4, 5, 6 h after treatment with Gemcitabine (G);
      b) in vivo expression of TPs genes after administration of Gemcitabine (a
      topoisomerases up-regulating drug) combined with the TPs inhibitors drugs (TID)
      Topotecan (T) and Etoposide (E), added to the culture beneath 1 h after TPD
      treatment. TPs mRNA expression was measured by quantitative real-time RT-PCR in
      PBMCs. RESULTS: The administration of 1-h infused G is followed by a fast rise of
      TPs expression (P > 0.0001 Student's t test, paired data, each patient control of
      himself); TPs inhibitors, sequentially given after G, highly reduced the TPs
      rising (P > 0.0001). CONCLUSIONS: G induces a TPs increase. A rationale might be
      available for combination chemotherapy (G plus TPs inhibitors). The study is
      ongoing to enroll further patients.

PMID- 16807459
TI  - Clinical studies of pemetrexed and gemcitabine combinations.
AB  - Pemetrexed (ALIMTA) is a novel multitargeted antifolate that inhibits thymidylate
      synthase, dihydrofolate reductase, and glycinamide ribonucleotide
      formyltransferase. This agent is broadly active in a wide variety of solid
      tumors, including breast cancer, bladder cancer, mesothelioma, non-small-cell
      lung cancer, pancreatic cancer and ovarian cancer. Pemetrexed has also shown
      clinically relevant activity in combination with gemcitabine. This combination
      has been, and continues to be evaluated for the treatment of a number of
      malignancies, including non-small cell lung and ovarian cancer. A recently
      published randomized trial of different sequences has identified the sequence of
      pemetrexed on day 1 followed by gemcitabine on day 1 and gemcitabine on day 8,
      every 21 days as the most efficacious and least toxic sequence.

PMID- 16807460
TI  - 10-year update on chemotherapy for non-small cell lung cancer.
AB  - BACKGROUND: A 1995 meta analysis of chemotherapy in patients with advanced non
      small cell carcinoma indicated clinical benefit from cisplatin based
      chemotherapy. Subsequent studies have aimed to increase the efficacy or decrease
      the toxicity of chemotherapy. PATIENT AND METHODS: Illustrative studies and meta
      analyses of different aspects of chemotherapy which have taken place over the
      last decade, are reviewed. RESULTS: The use of novel (third generation)
      chemotherapy agents has resulted in a further increase in patient survival.
      Gemcitabine was shown to be associated with an increase in progression free
      survival when compared to other third generation agents as well as a strong
      tendency to increased overall survival. An increase in survival was also shown
      with doublet chemotherapy regimes as compared to the use of single agents only.
      The use of triplet agent chemotherapy results in no further increased survival,
      but increased toxicity. Cisplatin is associated with increased survival over
      carboplatin based chemotherapy regimens when third generation agents are used,
      but increased nausea and vomiting. Non-platin third generation combinations give
      equivalent survival to platin-based regimens. CONCLUSIONS: First line
      chemotherapy given to patients with advanced NSCLC should be two-drug combination
      regimen. Non-platin containing regimens may be used as an alternative to platinum
      based regimens in the first line.

PMID- 16807461
TI  - Development of gemcitabine in non-small cell lung cancer: the Italian
      contribution.
AB  - Gemcitabine, a pyrimidine nucleoside antimetabolite, is one of the most promising
      new cytotoxic agents. The drug has shown activity in a variety of solid tumors,
      but appears to be most active in the treatment of non-small cell lung cancer. In
      this disease, several Italian investigators have evaluated gemcitabine in phase
      II and III clinical trials. Due to preclinical synergism with cisplatin, the
      Italian Lung Cancer Project played an important role to assess the efficacy and
      activity of the gemcitabine-cisplatin combination along with the best doses and
      schedule to adopt, thus leading to gemcitabine approval for first line treatment
      of advanced non-small cell lung cancer. Several Italian studies have also
      investigated gemcitabine non-platinum based combinations, gemcitabine in third
      generation platinum-based triplets and gemcitabine as second line therapy, but
      all these studies led to conflicting and inconclusive results. The low toxicity
      profile makes the drug a valid option for unfit and elderly patients. The
      Multicenter Italian Lung Cancer in the Elderly Study was a phase III randomized
      trial conducted in elderly patients with advanced non-small cell lung cancer that
      showed that single agent gemcitabine is at least as effective as either single
      agent vinorelbine or the combination of gemcitabine and vinorelbine. In the
      neoadjuvant treatment of stage III disease, a number of phase II studies with
      third generation platinum-based doublets or triplets have been conducted by
      Italian investigators with encouraging results. Current clinical trials are
      addressing the role of gemcitabine in combination with new targeted therapies.
      Future studies should be designed in order to identify subgroups of patients who
      are more likely to benefit from gemcitabine chemotherapy.

PMID- 16807462
TI  - Simplified gemcitabine and platin regimen in patients with advanced or metastatic
      non-small cell lung cancer (NSCLC) to be proposed as neoadjuvant therapy.
AB  - BACKGROUND: Chemotherapy of non-small-cell lung cancer (NSCLC) has been improved
      by the use of cis-platin (P) and the pyrimidine antimetabolite gemcitabine (G)
      (2',2'-difluorodeoxycytidine). GP regimens currently used in Italy for NSCLC were
      and are mainly based on G day 1, 8 and 15; P on day 2, every 28 days (4 Day
      Hospital admissions per cycle). However, the third G dose is frequently omitted
      because of myelo-toxicity, with a consistent dose decrease of both G and P in
      comparison with the intended dose. The 24-h lag time from 1(st) G and P has not
      reasonable clinical pharmacology base. AIM OF THE STUDY: To have a simplified GP
      regimen based on two Day-Hospital admissions per cycle, with G on day 1 and 8, P
      after G on day 8; every 21 days, with the goal to use it in the neoadjuvant
      setting. MATERIAL AND METHODS: The study was designed as a controlled,
      prospective, multicentre investigation, based on G (1500 mg/m(2)) on day 1 and 8,
      and P (100 mg/m(2)) on day 8 immediately following G, administered on a 3-week
      cycle. Quality of life (EORTC) was valuated in 46 patients out of 95 valuable
      patients. Restaging procedures were repeated after the 3rd and the 6th cycle.
      RESULTS: Enrolled patients were 105 (stage IV: 63: IIIB: 29; IIIA: 13). GP cycles
      were 488 (1 to 6 per patient) 95 patients had at least 3 cycles and 59 of them
      had further 3 cycles. Myelotoxicity >or= g3 was mainly neutropenia, easily
      amenable with symptomatic and GCSF therapies (12.6% neutropenic fever); PNS
      toxicity occurred in 17.9% of patients. QoL was ameliorated (P < 0.05). Therapy
      was tolerable and gave a Response Rate (RR) of 52.3% after 3 cycles (Intention-to
      treat analysis) and of 57.9% in 95 valuable patients who received at least 3
      therapy cycles. CONCLUSION: Present results confirm a good efficacy and/or
      synergism of G to P, with G on day 1 and 8 and P on day 8. This two day-hospital
      admissions regimen is at least as good as more complex GP regimens, and may be
      proposed in the neoadjuvant setting.

PMID- 16807463
TI  - Chemo-radiotherapy in non-small cell lung cancer: the role of gemcitabine.
AB  - Gemcitabine (2'-2'-difluorodeoxycytidine) is a well-known cytotoxic drug and a
      potent radio-enhancer. We herein report the in vitro evidence of its activity,
      and the clinical experiences when this drug is administered concurrently with
      radiation. The phase I-II trials are analyzed, focusing on the recent ability to
      deliver irradiation with low incidence of side effects.

PMID- 16807464
TI  - Neo-adjuvant chemotherapy in non-small cell lung cancer (NSCLC).

PMID- 16807465
TI  - Current status of adjuvant chemotherapy in NSCLC.

PMID- 16807466
TI  - First line chemotherapy in advanced or metastatic NSCLC.
AB  - The lung cancer global incidence has regularly increased during the last decades.
      Non Small Cell Lung Cancer (NSCLC) accounts for approximately 80% of all lung
      tumors. Different schedules including cisplatin plus gemcitabine or vinorelbine
      or paclitaxel or docetaxel or irinotecan showed advantages in terms of response
      rate, toxicity and quality of life, but little improvement in terms of survival.
      Some advantage was documented in favour of the combination including cisplatin
      plus a new drug versus monochemotherapy with new drugs. The large phase III
      studies performed with doublets containing new drugs and platinum are not free of
      criticism but in summary the research involving more than 3000 patients failed to
      indicate a standard regimen. With the aim of strengthen the phase III studies
      results, a meta-analysis tested the survival outcomes of published randomized
      trials, analysing the effects of the combination of gemcitabine and platinum
      compounds versus any platinum-based regimens. Gemcitabine-platinum combinations
      appear to offer a statistically significant superior efficacy in terms of overall
      survival and progression free survival as compared to other platinum-based
      regimens. Considering the palliative role of chemotherapy in advanced NSCLC and
      in order to reduce toxicity, not cisplatin-containing regimens were investigated.
      The results support the suggestion from the last ASCO guidelines: first-line
      chemotherapy of advanced NSCLC should be a two-drug combination regimen and not
      platin-based chemotherapy may be used as alternative to platinum-based regimens.
      The new frontier is represented by pharmacogenomic. The potential benefits of the
      pharmacogenomic approach lay in the possibility of predicting the patient
      chemotherapy response developing customized chemotherapeutic combinations and
      limiting severe side effects.

PMID- 16807467
TI  - Second-line chemotherapy for non-small cell lung cancer.
AB  - Despite being considered a standard of care, administration of second-line
      chemotherapy for non-small cell lung cancer is limited to patients in good
      performance status (ECOG PS 0-1) and to selected patients with PS 2. Drugs
      currently approved by FDA in this setting are docetaxel, gefitinib, erlotinib and
      pemetrexed, while in Europe those registered with this indication are only
      docetaxel and pemetrexed. This short review will focus on the role of pemetrexed,
      from the controlled phase II trial, to the development of the vitamin
      supplementation strategy to decrease toxicity, to the large phase III
      registration trial undertaken vs. the standard docetaxel. Moreover, the huge
      patient material collected during this latter trial has lead to further analyses
      to clarify several aspects of second-line treatment, from toxicity to quality of
      life assessment, to its role in elderly patients and to the direct translation in
      terms of costs. Finally, we will give a brief overview on current trials, that
      mainly explore the possibility to raise pemetrexed dose, and thus to increase its
      activity while maintaining an acceptable toxicity.

PMID- 16807468
TI  - Cellular pharmacology of gemcitabine.
AB  - Gemcitabine (2',2'-difluoro 2'-deoxycytidine, dFdC) is the most important
      cytidine analogue developed since cytosine arabinoside (Ara-C). The evidence of
      its potent antitumor activity in a wide spectrum of in vitro and in vivo tumor
      models has been successfully confirmed in the clinical setting. Despite
      structural and pharmacological similarities to Ara-C, gemcitabine displays
      distinctive features of cellular pharmacology, metabolism and mechanism of
      action. Following influx through the cell membrane via nucleoside transporters,
      gemcitabine undergoes complex intracellular conversion to the nucleotides
      gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP) responsible for its
      cytotoxic actions. The cytotoxic activity of gemcitabine may be the result of
      several actions on DNA synthesis. dFdCTP competes with deoxycytidine triphosphate
      (dCTP) as an inhibitor of DNA polymerase. dFdCDP is a potent inhibitor of
      ribonucleoside reductase, resulting in depletion of deoxyribonucleotide pools
      necessary for DNA synthesis and, thereby potentiating the effects of dFdCTP.
      dFdCTP is incorporated into DNA and after the incorporation of one more
      nucleotide leads to DNA strand termination. This extra nucleotide may be
      important in hiding the dFdCTP from DNA repair enzymes, as incorporation of
      dFdCTP into DNA appears to be resistant to the normal mechanisms of DNA repair.
      Gemcitabine can be effectively inactivated mainly by the action of deoxycytidine
      deaminase to 2,2'-difluorodeoxyuridine. Also, 5'-nucleotidase opposes the action
      of nucleoside kinases by catalysing the conversion of nucleotides back to
      nucleosides. Additional sites of action and self-potentiating effects have been
      described. Evidence that up- or down-regulation of the multiple membrane
      transporters, target enzymes, enzymes involved in the metabolism of gemcitabine
      and alterations in the apoptotic pathways may confer sensitivity/resistance to
      this drug, has been provided in experimental models and more recently also in the
      clinical setting. Synergism between gemcitabine and several other antineoplastic
      agents has been demonstrated in experimental models based on specific
      pharmacodynamic interactions. Knowledge of gemcitabine cellular pharmacology and
      its molecular mechanisms of resistance and drug interaction may thus be pivotal
      to a more rational clinical use of this drug in combination regimens and in
      tailored therapy.

PMID- 16807469
TI  - Chemotherapy of advanced NSCLC in special patient population.
AB  - The elderly and patients with Performance Status (PS) of 2, constitute the so
      called special patient population. The tolerability of chemotherapy in this
      population is globally worse, and treatment approaches should be different.
      Platinum-based combination chemotherapy is currently recommended as the standard
      treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its
      role in special patient population is controversial. The best treatment for
      elderly patients with advanced NSCLC is still debated. In the first randomized
      study dedicated to elderly NSCLC patients, single-agent vinorelbine showed
      superiority over supportive care alone, both in terms of survival and quality of
      life. In a large randomized trial, gemcitabine plus vinorelbine failed to show
      any advantage over either agent alone. Subset analyses suggest that the efficacy
      of platinum-based combination chemotherapy is similar in fit older and younger
      patients, with an acceptable increase in toxicity for elderly patients. However,
      the role of platin-based chemotherapy needs to be defined in prospective
      randomised trials. With the current evidence, single-agent chemotherapy with a
      third-generation drug (vinorelbine, gemcitabine, taxanes) should be the
      recommended option for non-selected elderly patients with advanced NSCLC. Also
      for PS2 patients there is no consensus on standard treatment. On the basis of
      current evidence, chemotherapy treatment appears justified for patients with
      advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine,
      taxanes) could be the preferred option, although carboplatin-based or low-dose
      cisplatin-based doublets may represent alternative options. Stronger evidence is
      expected from new clinical research specifically focused on PS2 patients. High
      priority should be given to the evaluation of tolerability and efficacy of
      platinum-based combinations and role of new targeted therapies.

PMID- 16807470
TI  - Non-small-cell lung cancer: which platinum for gemcitabine?

PMID- 16807471
TI  - Non-platinum combination of gemcitabine in NSCLC.

PMID- 16807472
TI  - Review of the pemetrexed and gemcitabine combination in patients with advanced
      stage non-small cell lung cancer.
AB  - Pemetrexed is a new multitargeted antifolate that can be easily administered as a
      10-min infusion every 3 weeks. The use of folic acid, vitamin B(12), and
      corticoid prophylaxis has significantly reduced pemetrexed-induced toxicity.
      Single-agent pemetrexed has shown antitumor activity in a wide range of solid
      tumors, including non-small cell lung cancer (NSCLC). Association with
      vinorelbine, cisplatin, carboplatin, and oxaliplatin have been tried, but the
      pemetrexed and gemcitabine combination, an easy to administer cisplatin-free
      doublet, has been documented in many phase 2 trials in the first-line treatment
      of advanced NSCLC. In vitro cytotoxic assays and phase I studies have defined
      several schedules of administration for pemetrexed and gemcitabine. The
      recommended dose is pemetrexed 500 mg/m(2) on day 1 or 8, and gemcitabine 1250
      mg/m(2) on day 1 and 8, but it is unknown if pemetrexed should precede or follow
      gemcitabine and at what time interval. Published studies have failed to show
      significant differences in overall survival times despites response rates
      oscillating between 15% and 41%. The main toxicities are neutropenia, fatigue,
      skin rashes and elevated transaminases and seem to occur with similar rates in
      the many phase 2 trials. Hopes for the future are in tailored chemotherapy, since
      molecular markers of sensitivity are available for gemcitabine and pemetrexed,
      allowing to determinate in the future which patients will be most likely to
      benefit from the gemcitabine-pemetrexed doublet.

PMID- 16807473
TI  - Novel targeted approaches in non-small cell lung cancer (NSCLC).

PMID- 16807474
TI  - The surgeon and the oncologist in non-small cell lung cancer (NSCLC).
AB  - A strict collaboration is necessary between the oncologist and the surgeon, both
      must know the respective problematic and competences and must contribute together
      to all phases of clinical management of patients affected by NSCLC.

PMID- 16807475
TI  - Chemotherapy advances in small cell lung cancer.

PMID- 16807476
TI  - Dementia with cerebrovascular disease.
AB  - In this case study, we review the symptoms, cognitive testing, brain imaging, and
      brain pathology of a woman with dementia, for whom the neuropathological findings
      suggest a prominent contribution of cerebrovascular disease. Vascular dementia is
      the term commonly used for persons with dementia resulting from strokes, either
      clinically evident or subclinical "silent" events. "Mixed dementia" is the term
      used when there is an admixture of pathological findings related to Alzheimer's
      disease (AD) and cerebrovascular disease, as in this situation. In some cases of
      mixed dementia, the pathological involvement of AD may be the principal
      contributory cause of the cognitive symptoms, and in others, the vascular changes
      may give the greater contribution.

PMID- 16807477
TI  - The age of cancer.
AB  - The biggest risk factor for cancer isn't smoking or bad diet or anything a person
      can avoid. It's growing old. New findings might help explain the connection
      between aging and cancer. According to the study, a gene that's faulty in a
      disorder that resembles accelerated aging shuts down in many cancers.

PMID- 16807478
TI  - Death-bed prophecy.
AB  - What's left to learn about aging? The burning question for many researchers is
      whether life-stretching pathways and genes from model organisms boost human life
      span. Researchers might be able to track down additional genes and pathways that
      adjust longevity by studying a broader range of organisms or by tracking the
      evolution of genes that promote aging. An alternative way to extend our lives
      might be to identify the genes behind late-life killers such as heart disease and
      diabetes. Lab animals last longer on a very low-cal diet, and scientists are
      probing whether humans can benefit from this austerity. Or better yet, perhaps
      researchers can design molecules that deliver the gain of calorie reduction
      without the pain. Scientists are also focusing on which parts of the cell incur
      damage as we age and how growth and reproduction tie in to longevity. The speed
      of the next round of advances will depend on whether movers and shakers in
      funding organizations recognize the importance of the research and are willing to
      pay for it.

PMID- 16807479
TI  - The role of mitochondria in conserved mechanisms of aging.
AB  - The European research project MiMage, supported by the European Community's Sixth
      Framework for Research and Technological Development, focuses on elucidating the
      role of mitochondria in conserved mechanisms of aging. This Perspective
      summarizes a selection of talks presented in April 2006 at the second MiMage
      symposium by members from participating laboratories and invited speakers.

PMID- 16807480
TI  - Aging on the job.
AB  - The older population is growing faster than the population as a whole. Paid work
      is the main mechanism for physical activity in humans. We, therefore, wanted to
      ascertain whether work practices (such as employment status and the types of
      tasks workers perform) follow the biological decline in physical activity that
      occurs with aging in humans and many other species. We recorded work practices in
      3352 adults in the Ivory Coast to establish how work burdens are distributed
      across different age groups in a community that is minimally fettered by legal
      constraints. We found a decrease in the amount of work performed with increasing
      age, and we found that elderly persons performed more skilled, less exothermic
      tasks than younger workers. These data mirror global workforce distribution
      trends expressed by age. If the trend continues, a major portion of the
      population will be unlikely to contribute to the labor force in the near future,
      producing potentially adverse economic consequences in some populations. Although
      the problem might be averted or at least minimized by implementing different
      employment policies, biological factors could overlay and supervene any economic
      planning.

PMID- 16807481
TI  - Developing a research agenda in biogerontology: physiological systems.
AB  - The Biology of Aging Program (BAP) at the National Institute on Aging supports
      research in many areas, including processes of cell senescence and apoptosis,
      genetic influences on aging, and how aging leads to tissue dysfunction. Several
      approaches to research on aging physiological systems are described, along with
      BAP programmatic efforts to enhance and support that research. Understanding the
      relation between aging and tissue dysfunction has led to new insights into how
      health can be improved for aged individuals.

PMID- 16807482
TI  - WRN's tenth anniversary.
AB  - Werner syndrome (WS) is a segmental progeroid syndrome in which patients display
      pleiotropic features of aging seen in the normal population. The advent of
      positional cloning in the 1990s markedly accelerated the identification of human
      disease-causing genes. In 1996, mutations in WRN, which was shown to encode a
      new, putative member of the family of RecQ DNA helicases, were identified in four
      patients as the cause of WS. Ten years after the identification of WRN, what have
      we learned about its role in WS, and its contribution to normal aging?

PMID- 16807483
TI  - A work in progress: the metabolic syndrome.
AB  - Metabolic syndrome refers to a constellation of risk factors for cardiovascular
      disease. They include elevated plasma glucose concentrations, dyslipidemia,
      hypertension, and abdominal obesity. These conditions typically occur during
      middle age or later in life. Although there is no clear consensus on the
      diagnosis of metabolic syndrome, it is a potentially important entity to
      recognize and manage once traditional cardiovascular risk factors, such as
      smoking, hypertension, dyslipidemia, and diabetes, have been treated
      individually. This Perspective summarizes our current knowledge of the metabolic
      syndrome. Lifestyle change, including diet and exercise, is probably the best
      available option for treating the metabolic syndrome. However, rigorous lifestyle
      interventions are difficult to implement outside of a clinical trial setting,
      especially among elderly patients.

PMID- 16807484
TI  - The unusual genetics of human longevity.
AB  - In no species other than humans do cultural, social, and biological factors
      interact with each other in modulating complex phenotypes. Thus, the
      identification of genetic factors that affect human longevity is a true
      challenge. The model of centenarians provides us a unique opportunity to tackle
      this challenge. In this Perspective, we discuss some recent findings (the impact
      of geography and demography on the longevity phenotype, the relationship between
      longevity and homozygosity, the role of the nuclear-mitochondrial genome cross
      talk) by which new ideas are suggested, such as the concept of a complex allele
      timing as a pivotal process in modulating the probability of achieving longevity.

PMID- 16807485
TI  - From bedside to bench: does mental and physical activity promote cognitive
      vitality in late life?
AB  - A wide range of animal and human studies provide evidence for the potential of
      physical and cognitive exercise in promoting cognitive health later in life. The
      effects of such activities on intermediate outcomes, such as cognitive
      performance, are becoming clearer, as are the molecular mechanisms involved.
      Physical and cognitive exercise might increase "cognitive reserve" and increase
      the overall health of the brain, thereby reducing or delaying cognitive
      impairment and dementia. However, conclusive evidence for such benefits is not
      yet established. The third annual Bedside to Bench conference, cosponsored by The
      American Geriatrics Society and the National Institutes of Health's National
      Institute on Aging, reviewed current knowledge regarding the role of physical and
      cognitive exercise in promoting cognitive vitality. Conference attendees
      identified gaps in our current understanding of these processes and recommended
      next steps for research. In particular, researchers will need to explore clinical
      issues related to the timing, intensity, and duration of various types and
      combinations of physical and cognitive activities in animal models to elucidate
      the mechanisms involved and inform the design of future human studies. The
      concept of the enriched environment currently employed in animal studies to
      promote physical activity, socialization, and problem solving should be explored
      in human studies.

PMID- 16807486
TI  - Targeting the role of the endosome in the pathophysiology of Alzheimer's disease:
      a strategy for treatment.
AB  - Membrane-bound endosomal vesicles play an integral role in multiple cellular
      events, including protein processing and turnover, and often critically regulate
      the cell-surface availability of receptors and other plasma membrane proteins in
      many different cell types. Neurons are no exception, being dependent on endosomal
      function for housekeeping and synaptic events. Growing evidence suggests a link
      between neuronal endosomal function and Alzheimer's disease (AD) pathophysiology.
      Endosomal abnormalities invariably occur within neurons in AD brains, and
      endocytic compartments are one likely site for the production of the pathogenic
      beta-amyloid peptide (Abeta), which accumulates within the brain during the
      disease and is generated by proteolytic processing of the amyloid precursor
      protein (APP). The enzymes and events involved in APP processing are appealing
      targets for therapeutic agents aimed at slowing or reversing the pathogenesis of
      AD. The neuronal endosome may well prove to be the intracellular site of action
      for inhibitors of beta-amyloidogenic APP processing. We present here the view
      that knowledge of the endosomal system in the disease can guide drug discovery of
      AD therapeutic agents.

PMID- 16807487
TI  - I come not to bury SAGE KE but to appraise It.
AB  - This article serves as a eulogy for the Science of Aging Knowledge Environment
      (SAGE KE). This online resource--Science's Web site on aging--is publishing its
      last issue today. The piece is a personal recollection of co-creating the site-
      and includes some thoughts on how the field of aging has changed over the last
      six years.

PMID- 16807488
TI  - Human deaths from avian influenza in Azerbaijan--further spread in birds
      worldwide.

PMID- 16807489
TI  - Cases of chikungunya imported into Europe.

PMID- 16807491
TI  - Comprehensive guidance to reduce infection risk from spa pools and whirlpool
      baths.

PMID- 16807490
TI  - First case of vCJD reported in a Japanese patient: update.

PMID- 16807492
TI  - Measuring teaching ability with the Rasch model by scaling a series of product
      and performance tasks.
AB  - Rasch measurement can provide a much needed solution to scaling teacher ability.
      Typically, decisions about teacher ability are based on dichotomously scored
      certification tests focused on knowledge of content or pedagogy. This paper
      presents early developmental work of a partial-credit teacher-ability scale of 42
      tasks (performances and products) with 348 rated items or criteria. The tasks and
      criteria are aligned with national and state standards for expected teacher
      knowledge and skills. These tasks are being used in about two-thirds of Florida
      school districts and are spreading to colleges of education. Over time there will
      be many variations in both tasks and criteria, but here we focus on the initial
      system and the Rasch model as part of the plan for development of the system.

PMID- 16807493
TI  - An introduction to the theory of unidimensional unfolding.
AB  - Despite its 55 year presence in the field of mathematical psychology, the theory
      of unidimensional unfolding remains an enigma for many psychometricians and
      applied practitioners. This paper is the first of a three part series; and it
      aims to introduce unidimensional unfolding theory. The paper begins with a simple
      hypothetical example presenting an idealised distinction between responses to
      cumulative and unfolding dichotomous items. This followed by an accessible
      presentation of the theory of unidimensional unfolding as first articulated by
      Clyde H. Coombs (1950, 1964). The concept of the single peaked preference
      function (Coombs and Avrunin, 1977) which underpins unfolding theory is then
      presented. The article then progresses to the class of Rasch (1960) based IRT
      models developed by Andrich (1995) and Luo (2001). It was shown these models
      propose arguments not inconsistent with Coombs's (1964) original theory. The
      presumption of additive structure in psychological attributes was concluded to be
      the key weakness of the theories of unidimensional unfolding discussed.

PMID- 16807494
TI  - Estimating person locations from partial credit data containing missing
      responses.
AB  - Certain assessment situations produce partial credit data. For instance,
      performance assessment items may utilize a rubric that assigns partial credit for
      some not completely correct responses. In some cases examinees may choose to not
      answer each question. This study investigated the effect of various strategies
      for handling these missing responses for estimating a respondent's location.
      These methods included ignoring the omitted response, selecting the "midpoint"
      category score, treating the omitted response as incorrect, hotdecking, and a
      likelihood-based approach. A simulation study was performed to examine the
      efficacy of these methods with the partial credit and generalized partial credit
      models. Expected a posteriori (EAP) ability estimation was used. Results showed
      that the Midpoint and Likelihood procedures performed the best of methods
      examined. In contrast, omitted responses should not be treated as incorrect nor
      ignored when estimating an examinee's proficiency using EAP. Implications for
      practitioners are discussed.

PMID- 16807495
TI  - Validation of a questionnaire used to assess safety and professionalism among
      arborists.
AB  - This article summarizes a validation study of an instrument designed to measure
      safety and professionalism practices of arborists. A sample of 386 arborists from
      the State of Louisiana responded to the 58-item questionnaire. Analyses focused
      on several aspects of Messick's validation framework. Structural validity
      evidence was provided by analyses that indicate that the measures are
      unidimensional. Content validity evidence was supported by generally high
      positive values of the biserial correlations and optimal values of standardized
      mean-square item fit indices. Substantive validity evidence was provided by
      analyses that support the use of the two-point rating scale and a rank ordering
      of item means that is consistent with substantive theory. Person fit indices
      indicated little misfit among measures. Support for the generalizability aspect
      of validity was provided by an acceptable level of internal consistency and
      fairly tight error bands around estimated arborist measures. Additionally, few
      items exhibited DIF. Finally, with respect to the external aspect of validity,
      group differences between arborist measures were consistent with substantive
      theory.

PMID- 16807496
TI  - How accurate are lexile text measures?
AB  - The Lexile Framework for Reading models comprehension as the difference between a
      reader measure and a text measure. Uncertainty in comprehension rates results
      from unreliability in reader measures and inaccuracy in text readability
      measures. Whole-text processing eliminates sampling error in text measures.
      However, Lexile text measures are imperfect due to misspecification of the Lexile
      theory. The standard deviation component associated with theory misspecification
      is estimated at 64L for a standard-length passage (approximately 125 words). A
      consequence is that standard errors for longer texts (2,500 to 150,000 words) are
      measured on the Lexile scale with uncertainties in the single digits.
      Uncertainties in expected comprehension rates are largely due to imprecision in
      reader ability and not inaccuracies in text readabilities.

PMID- 16807498
TI  - Multicomponent latent trait models for complex tasks.
AB  - Contemporary views on cognitive theory (e.g., Sternberg and Perez, 2005) regard
      typical measurement tasks, such as ability and achievement test items,
      multidimensional, rather than unidimensional. Assessing the levels and the
      sources of multidimensionality in an item domain is important for item selection
      as well as for item revision and development. In this paper, multicomponent
      latent trait models (MLTM) and traditional multidimensional item response theory
      models are described mathematically and compared for the nature of the dimensions
      that can be estimated. Then, some applications are presented to provide examples
      of MLTM. Last, practical estimation procedures are described, along with syntax,
      for the estimation of MLTM and a related model.

PMID- 16807497
TI  - Rasch modeling of the structure of health risk behavior in South african
      adolescents.
AB  - The study used Rasch analysis to investigate the presence of a syndrome of health
      risk behavior in South African adolescents. A total of 2186 in-school adolescents
      participated in the study (males = 1077; females = 1119; age range = 12-16 years;
      median = 13 years). The data are baseline from a longitudinal study of a leisure
      based drug abuse and HIV/AIDS prevention program at Mitchell's Plain in Cape
      Town, South Africa. The adolescents completed a self-report measure on various
      health risk vulnerabilities, including use of alcohol, tobacco and other drugs
      (ATOD), co-occurrence of penetrative sex with use of ATOD, health related self
      efficacy, personal beliefs about health, peer perceptions, and use of
      contraceptives. The Rasch analysis calibrated data on 50 items from the aforesaid
      conceptually distinct health risk domains. Infit and Outfit mean square
      statistics and principal components analysis of the standardized residuals
      suggested a fit of the data to the unidimensional Rasch measurement model. The
      findings support a syndrome view of health risk in teenagers as proposed by
      problem behavior theory.

PMID- 16807499
TI  - Differentiation and regeneration of adrenal tissues: An initial step toward
      regeneration therapy for steroid insufficiency.
AB  - In animal experiments, adrenal cortical tissue has been successfully regenerated
      through xenotransplantation of cloned adrenocortical cells, suggesting that the
      intraadrenal stem cells required for such tissue formation may be present in the
      adrenal cortex. Stable expression of Ad4BP/SF-1, a key factor for adrenal and
      gonadal development and steroidogenesis, has been shown to direct embryonic stem
      cells toward the steroidogenic lineage. However, this steroidogenic capacity was
      very limited since progesterone was only produced in the presence of an exogenous
      substrate. Bone marrow mesenchymal cells are thought to contain pluripotent
      progenitor cells, which differentiate into multiple lineages. We have
      demonstrated that adenovirus-mediated forced expression of SF-1 in long-term
      cultured bone marrow cells can produce steroidogenic cells with the capacity for
      de novo synthesis of various steroid hormones in response to ACTH. This discovery
      may represent the first step in autologous cell transplantation therapy for
      patients with steroid hormone deficiency.

PMID- 16807500
TI  - Follicular thyroid carcinoma: From diagnosis to treatment.
AB  - Unusual presentations with bone, lung or soft tissue metastases in initial
      diagnosis of follicular thyroid carcinoma have been reported occasionally. This
      implies how difficult it is to diagnosis this type of cancer at the pre-operative
      or intra-operative stage of treatment. Fine needle aspiration cytology has been
      shown to be an ineffective method for diagnosing vascular or capsule invasion of
      follicular thyroid cancer. Multiple frozen sections, usually 5 to 12 depending on
      the size of the tumor, can achieve a diagnostic accuracy of 98%. Clinical
      application of various gene expressions in thyroid follicular tumors by needle
      aspiration using in situ hybridization requires further investigation. Although
      radioactive iodide (131I) has been used as the standard treatment for follicular
      thyroid carcinoma with distant metastases, the effectiveness of 131I treatment
      for follicular thyroid carcinoma depends on the differentiation of cancer cells.
      The possibility of 131I for thyroid remnant ablation replacing a secondary
      operation for follicular thyroid carcinoma has been debated. Recent studies
      applied more expressions of sodium iodide symporters to attain the effect of 131I
      treatment and slow the proliferation of thyroid cancer cell which, in turn, slows
      the progression of follicular carcinoma. Consensus for the surgical procedures
      for the specific prognostic risks for follicular thyroid carcinoma is needed.
      Dedifferentiated, anti-angiogenic, or gene therapies for follicular thyroid
      cancer with distant metastases or anaplastic transformation comprise the
      principal directions in future research for this cancer.

PMID- 16807501
TI  - TIRF microscopy analysis of the mechanism of insulin exocytosis.

PMID- 16807502
TI  - Effect of exposure duration of ovaries and oocytes at ambient temperature on
      parthenogenetic development of porcine follicular oocytes.
AB  - This study was conducted to evaluate the effects of exposing porcine ovaries to
      30-33 C during transportation for 4 h and subsequently room temperature (25 C)
      for 6 h of storage on in vitro maturation (IVM) and subsequent parthenogenetic
      development of oocytes collected from the ovaries. After IVM, oocytes having a
      tight oopalsm membrane and no signs of degeneration were exposed to Dulbecco's
      phosphate-buffered saline (DPBS) with 7% ethanol (v/v) for 7 min to induce
      parthenogenetic activation. Moreover, we also determined whether exposure of the
      collected oocytes to room temperature for 1, 2 and 4 h in DPBS or porcine
      follicular fluid (pFF) affected parthenogenetic development. When porcine ovaries
      were stored after transportation, oocytes collected from the stored ovaries
      showed a significantly higher rate of degeneration after 65 h of IVM (58.4%) and
      a significantly lower rate of cleavage after parthenogenetic activation (40.1%)
      than oocytes collected from ovaries immediately after transportation (38.9% and
      47.4%, respectively). However, there was no significant difference in
      developmental rates to the morula and blastocyst stages between these two groups
      (14.4% and 14.3%, respectively). The duration of preservation, 1, 2, and 4 h, of
      oocytes in DPBS did not affect parthenogenetic development. In contrast, when
      preserved for 4 h in pFF, the developmental rates of the oocytes were
      significantly decreased. This suggested that some factor(s) in follicular fluid
      affects the developmental rate of oocytes with the passage of time in ambient
      conditions. These results suggest that even after 6 h storage of ovaries, oocytes
      having normal morphology after IVM have the same rate of parthenogenetic
      development as oocytes collected from ovaries just after 4 h of transportation,
      except for a lower cleavage rate, and that exposure of oocytes to room
      temperature for 4 h in DPBS does not affect their parthenogenetic developmental
      competence.

PMID- 16807504
TI  - Collateral uterine blood flow in Holstein cows during the third trimester of
      pregnancy.
AB  - Blood flow to the gravid and nongravid uterine horns of four multiparous Holstein
      cows (mean +/- SD, BW=641.8 +/- 95.4 kg; age=4.8 +/- 1.2 years; parity=3.0 +/-
      1.2) was measured on days 225, 248, and 266 of gestation. Surgery was conducted
      on day 214.5 +/- 4.0 of gestation through the flank of the standing cows. Transit
      time ultrasonic flow probes (diameter 12 or 14 mm) were fitted surgically around
      the uterine arteries of each cow. Surgery was completed within two hours of
      anesthesia, and the animals recovered rapidly following surgery. Uterine blood
      flow (UBF, l/min) was recorded at 10 sec intervals for approximately 23.5 hours;
      these values were averaged to determine UBF. The mean gravid UBF was
      significantly (P<0.05) greater than the nongravid UBF in this study. The range of
      the gravid and nongravid UBFs varied from 3.61 to 14.05 and 0.72 to 6.54 l/min,
      respectively. There were no changes (P>0.1) in the mean gravid and nongravid UBFs
      from day 225 to 266 of gestation.

PMID- 16807503
TI  - Expression of inhibin/activin subunits in the ovaries of fetal and neonatal mice.
AB  - In the present study, the expression of inhibin/activin subunits in the mouse
      ovary from 13 days post-coitus (dpc) to 30 days postpartum (dpp) was
      investigated. Circulating FSH, LH, inhibin A, and inhibin B in neonatal to 30 dpp
      ovaries were measured. Inhibin/activin subunits (alpha, beta(A), beta(B) ) were
      weakly stained in 13 dpc ovarian stromal cells and increased with age. Inhibin
      alpha subunit was immunolocalized in follicular granulosa cells at each
      developmental stage. In 30 dpp ovaries, several large antral follicles were
      strongly stained for inhibin alpha subunit. Inhibin beta(A) subunit was weakly
      immunolocalized in granulosa cells until 20 dpp. Moreover, 2 to 3 antral
      follicles from 20 to 30 dpp were strongly stained for inhibin beta(A) subunit.
      There was relatively high immunoactivity for inhibin beta(B) subunit in neonatal
      to 30 dpp mouse ovaries. All three inhibin subunits were stained in theca
      interstitial cells from 15 dpp onward. RIA data showed that a temporal increase
      in circulating FSH occurred around 10 dpp, while the plasma concentrations of LH
      were sustained at a relatively higher level from 8 to 15 dpp. Inhibin B was
      detectable in circulation early at 1 dpp (day of birth), and a clear increase in
      inhibin B occurred around 8 dpp. Circulating inhibin B gradually increased from
      20 dpp to 30 dpp, indicating a negative correlation with FSH. Inhibin A levels
      were only measured on 25 and 30 dpp, and the levels were low. These results
      suggest that inhibins play an important role in early folliculogenesis in mice.
      In addition, inhibin B seems to be the main functional isoform from the neonatal
      to prepubertal stage in the mouse ovary.

PMID- 16807505
TI  - Effect of potassium simplex optimization medium and NCSU23 supplemented with beta
      mercaptoethanol and amino acids of in vitro fertilized porcine embryos.
AB  - The present study was conducted to examine the comparative efficacy of potassium
      simplex optimization medium (KSOM) and North Carolina State University (NCSU)-23
      medium supplemented with beta-mercaptoethanol (beta-ME) and amino acids (AA) on
      the developmental competence of porcine in vitro fertilized (IVF) embryos. Four
      experiments were conducted. KSOM and NCSU-23 medium were used to culture porcine
      parthenogenetic (Exp. 1) and IVF (Exp. 2) embryos. KSOM and NCSU-23 were equally
      effective in supporting porcine parthenogenetic and IVF embryo development from
      the 1-cell stage to blastocysts. The NCSU-23 medium (Exp. 3) and KSOM (Exp. 4)
      were supplemented with amino acid (AA; 5 microl/ml non-essential amino acids + 10
      microl/ml essential amino acids) and/or 10 microM beta-mercaptoethanol (beta-ME).
      The quality of blastocysts from Exp. 3 and 4 was evaluated by counting the number
      of total cells and determining the ratio of the inner cell mass (ICM) to
      trophoectoderm (TE) cells. Supplementing with AA and beta-ME or beta-ME alone in
      NCSU-23 produced significant (p<0.05) differences in terms of rate of cleavage to
      the 2- to 4- cell (80.8 to 85.4% vs. 73.6%) and blastocyst (30.4 to 30.5 vs.
      23.5%) stages and the number of TE (51.4 to 53.8 vs. 35.8) and total cells (67.2
      to 71.2 to 48.8) over the control group. On the other hand, supplementing KSOM
      with AA and/or beta-ME produced significant (p<0.05) differences in terms of rate
      of cleavage to the 2- to 4-cell (78.8% vs. 67.7%) and morula (57.8% vs. 46.3%)
      stages and the number of ICM (18.6 to 19.2 vs. 11.6) and total cells (62.8 to
      70.6 vs. 42.8) over control group. In conclusion, our study demonstrates that
      both KSOM and NCSU-23 medium supplemented with AA and beta-ME and/or only beta-ME
      alone are superior to normal KSOM and NCSU-23 for porcine IVF embryo culture in
      terms of embryo developmental competence and quality.

PMID- 16807506
TI  - Application of laser-assisted zona drilling to in vitro fertilization of
      cryopreserved mouse oocytes with spermatozoa from a subfertile transgenic mouse.
AB  - Development of assisted reproductive technologies is necessary to obtain
      fertilized oocytes in a subfertile transgenic mouse strain. Here, we showed the
      application of laser-assisted drilling of the zona pellucida to in vitro
      fertilization of cryopreserved mouse oocytes with sperm from subfertile
      transgenic mice (C57BL/6N-Tg(UCP/FAD2)U8 strain). After cryopreservation by
      vitrification, the recovery and survival rates of the zona-drilled mouse oocytes
      were 97% (97/100) and 94% (91/97), respectively. In vitro fertilization of the
      cryopreserved zona-drilled mouse oocytes with sperm from the subfertile
      transgenic mice was greatly facilitated (60%, 55/91) compared to that of the
      cryopreserved zona-intact mouse oocytes (11%, 81/768). In vitro fertilized
      embryos that developed to the 2-cell stage were again cryopreserved by
      vitrification, and after warming they were transferred into recipient females.
      Subsequently, six viable offspring were delivered, and all were confirmed to be
      transgenic mice. These results indicate that laser-assisted zona drilling of
      oocytes combined with cryopreservation by vitrification may be a useful approach
      for large-scale production of in vitro fertilized embryos for managing transgenic
      mouse strains with reproductive disabilities such as subfertile sperm.

PMID- 16807507
TI  - Reproductive and growth performance in Jin Hua pigs cloned from somatic cell
      nuclei and the meat quality of their offspring.
AB  - Somatic cell cloning is expected to be a valuable method for conserving genetic
      resources in pigs. In this study, we compared the reproductive and growth
      performance of Jin Hua cloned pigs with that of naturally bred Jin Hua pigs. In
      addition, we generated offspring from the cloned sows and examined the
      productivity and quality of meat in the progeny. The birth weights and growth
      rates of somatic cell-cloned pigs were similar to those of Jin Hua pigs. The
      cloned pigs reached puberty very early, and this is typical of the Jin Hua breed.
      Furthermore, reproductive performance, in terms of traits such as gestation
      period, litter size, and raising rate in the cloned pigs were similar to Jin Hua
      pigs. Although the offspring of the cloned (OC) pigs had lower birth weights than
      the Jin Hua breed, the daily weight gain of the OC pigs was significantly higher,
      especially at the finishing stage. The carcass quality of the OC pigs had similar
      characteristics to the Jin Hua breed, namely thick back fat and a small loin
      area. Furthermore, the meat qualities of the OC pigs were similar to those of Jin
      Hua pigs in terms of intramuscular fat content and tenderness. These results
      demonstrate that cloned pigs and their offspring were similar to the Jin Hua
      breed in most of the growth, reproductive, and meat productive performances. This
      strongly suggests that pigs cloned from somatic cell nuclei have the potential to
      be a valuable genetic resource for breeding.

PMID- 16807508
TI  - Autoimmunity: basic mechanisms and implications in endocrine diseases. Part I.
AB  - Autoimmunity implies disturbances at several levels of the immune control. Self
      tolerance and discrimination between self and non-self synergize to avoid the
      development of autoimmunity. Negative selection in the thymus, the transcription
      factor AIRE, CD4+CD25+ regulatory T cells, and dendritic cells cooperate to
      produce and maintain tolerance. Cytokines modulate deriving immune processes and
      influence the local micro-environment. Multiple mechanisms are involved in
      tolerance breakdown: genetic factors (major histocompatibility complex
      haplotypes, polymorphisms in the cytotoxic T lymphocyte antigen gene and
      epigenetic alterations), environmental factors (mainly infections), impaired
      apoptosis, and the emergence of autoreactive naive lymphocytes. These events may
      be involved in the pathogenesis of endocrine diseases at several levels.

PMID- 16807509
TI  - Autoimmunity: basic mechanisms and implications in endocrine diseases. Part II.
AB  - Regulation of the immune response to self-antigens is a complex process that
      involves maintaining self-tolerance while preserving the capacity to exert an
      effective immune response. The primary mechanism that leads to self-tolerance is
      central tolerance. However, potential pathogenic autoreactive lymphocytes are
      normally present in the periphery of all individuals. This suggests the existence
      of mechanisms of peripheral tolerance that prevent the initiation of autoimmune
      diseases by limiting the activation of autoreactive lymphocytes. If these
      mechanisms of peripheral tolerance are impaired, the autoreactive lymphocytes may
      be activated and autoimmune diseases can develop. Several processes are involved
      in the maintenance of peripheral tolerance: the active suppression mediated by
      regulatory T cell populations, the different maturation state of antigen
      presenting cells presenting the autoantigen to autoreactive lymphocytes, inducing
      tolerance instead of cell activation, the characteristics of B cell populations.
      A deeper comprehension of these mechanisms may lead to important therapeutic
      applications, such as the development of cellular vaccines for organ-specific
      autoimmune diseases. In addition, autoimmunity does not always have pathological
      consequences, but may exert a protective function, as suggested by several
      observations on the beneficial role of autoreactive T cells in central nervous
      system injury.

PMID- 16807512
TI  - The future of stem cells in liver diseases.
AB  - Preliminary experience with clinical hepatocyte transplantation during the past
      decade has provided proof of concept that cell therapy can be effective for the
      treatment of some liver diseases. Recent progress in cell biology resulting in
      the isolation and characterization of hepatic stem cells and progenitor cells
      further increased the expectation for a new approach to the treatment of genetic
      and chronic liver disease. Several potential sources have been identified of
      hepatic stem/ progenitor cells exhibiting both differentiation towards the
      hepatic lineage in vitro and hepatic parenchymal repopulation with liver-specific
      metabolic activity in liver-injured animal models. However, a few of these
      results proved to be poorly reproducible in different laboratories, and it was
      recognized that some initial optimistic conclusions were drawn from incorrect
      interpretation of experimental data or from insufficient knowledge of the
      mechanisms involved in tissue regeneration. Moreover, only modest results have
      emerged so far from ongoing clinical experience involving the use of putative
      stem cells in liver disease. There is much need for a joined effort to
      concentrate the resources on a specific cell population, in order to better
      characterize its function, to assess its safety and to develop better focused
      clinical trials. In conclusion, while the biological features of stem cells still
      justify the hope for future clinical applications, hepatic stem cell therapy has
      still a long way to go from bench to bedside.

PMID- 16807510
TI  - Heparin-induced thrombocytopenia in a pediatric patient receiving extracorporeal
      membrane oxygenation managed with argatroban.
AB  - INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is rare in the pediatric
      population, with a majority occurring in the pediatric intensive care unit
      setting. All cases reported to date have been associated with the use of
      unfractionated heparin. Because unfractionated heparin is the anticoagulant of
      choice for extracorporeal membrane oxygenation (ECMO) and other extracorporeal
      therapies, the development of HIT in these patients can be devastating, making
      management problematic. We report a case of HIT type II with evidence of small
      vessel arterial thrombosis in a 17-month-old boy receiving ECMO and continuous
      renal replacement therapy successfully treated with argatroban. CASE: The patient
      was a 17-month-old boy with severe hypercapnic and hypoxemic respiratory failure
      secondary to asthma and mucus plugging that failed conventional and
      unconventional ventilation. Venovenous ECMO was initiated, and within 24 hrs,
      there was a precipitous decrease in the platelet count, with the development of
      cutaneous ischemia involving his lower limbs. Argatroban was started and the
      child maintained on ECMO and continuous renal replacement therapy, with
      resolution of the cutaneous ischemia and recovery of the platelet count. Heparin
      associated antibodies were positive. DISCUSSION: HIT is rare in the pediatric
      population. Recognition of HIT is vital because withdrawal of heparin is the
      first and most important therapy. For patients receiving ECMO or continuous renal
      replacement therapy who develop HIT, synthetic thrombin inhibitors have been
      reported as an alternative. However, little information on their use in
      extracorporeal life support has been published, particularly in the pediatric
      population. CONCLUSION: This report documents a pediatric case of HIT type II
      successfully treated with argatroban, allowing continuation of the ECMO and
      continuous renal replacement therapy therapy, with resolution of the cutaneous
      ischemia and thrombocytopenia.

PMID- 16807513
TI  - Post-liver transplantation medical complications.
AB  - Liver transplantation (LT) is widely accepted as an effective therapeutic
      modality for a variety of irreversible acute and chronic liver disease. The
      success of liver transplantation has increased steadily over the last two decades
      and several advances have been made since the first human liver transplant. This
      procedure has become routine with an excellent outcome in terms of both quality
      and length of survival. The results of liver transplantation have improved due to
      advances in perioperative technique, a better understanding of the course and
      prognosis of several liver disease, improved immunosuppressive therapy and more
      effective postoperative care. Nevertheless, improved tools detecting under
      immunosuppression, new strategies against viral infections(i.e. cytomegalovirus),
      and new immunosuppressive drugs will probably even prevent further graft
      dysfunction in the future. However, complications are common in the early and
      long term period and contribute to significant morbidity and mortality. One of
      the major challenges facing the transplant community is the increasing metabolic
      complications that are now affecting quality of life and long-term survival.
      Thus, knowledge of complications that emerge during follow up period, early and
      accurate establishment of diagnosis, and prompt institution of appropriate
      interventions are essential for optimal patient and graft outcome. This review
      summarizes available data about medical complications of the early and long term
      follow up.

PMID- 16807514
TI  - Beta blockers in portal hypertension. Are they really a good option?
AB  - Non-selective beta blockers are very useful drugs in preventing first variceal
      bleeding and re-bleeding in patients with cirrhosis. These drugs work in two
      ways: 1) by blocking beta1 receptors and reducing cardiac output, and 2) by
      blocking beta2 receptors, producing splanchnic vasoconstriction and reducing
      portal flow. Consequently, they reduce portal pressure. In primary prophylaxis,
      beta blockers reduced the bleeding risk from 30 to 15%; in secondary prophylaxis,
      this risk decreased from 60 to 42% in the first year. Heart rate decrease does
      not necessary correlate with reduction in hepatic venous pressure gradient
      (HVPG). When this gradient is reduced to less than 12 mmHg, the patient will not
      bleed; when this is reduced > 20% from basal values bleeding risk is extremely
      low, estimated at 9% at 2 years. The only way to know whether the patient has
      become a responder is to measure the HVPG. Additionally, by means of this method
      we also can identify the non-responders, who have a higher rate of re-bleeding,
      between 54 and 64%, and can attempt to utilize a more aggressive therapy, such as
      adding isosorbide mononitrate to the beta blocker or combining the beta blocker
      with endoscopic ligation. These options are discussed in the present review.

PMID- 16807515
TI  - Obesity-related leptin receptor polymorphisms and gallstones disease.
AB  - OBJECTIVE: Investigate the association between polymorphisms in the leptin
      receptor gene associated with obesity and gallstone disease. DESIGN: We conducted
      a cross-sectional study, carried out at a tertiary setting. SUBJECTS: We enrolled
      97 subjects, comprising 54 subjects with gallstones (cases) and 43 controls
      (without gallstones). MEASUREMENTS: Diet was assessed using a validated
      questionnaire for the Mexican population. Body mass index, waist circumference,
      serum glucose,insulin, leptin, lipids and lipoproteins levels were measured.
      Insulin resistance was calculated by HOMA-IR. Genomic DNA was isolated from
      lymphoblastoid cells, and Q223R and K656N polymorphisms in the leptin receptor
      gene were typed using polymerase chain reaction. Unconditional univariate
      logistic regression analysis was conducted to estimate the probability of
      gallstone disease associated with the polymorphisms as main effect. RESULTS:
      Cases were different in gender(40.74% males in cases vs 74.41% in controls; p <
      0.001), older (49.74 vs 44.83 years; p < 0.05), and had more body fat (32.34% vs
      28.14%; p = 0.01). Individuals carrying the polymorphism Q223R exhibited a higher
      BMI (28.44 +/- 6.6 kg/m2 vs 25.94 +/- 3.67 kg/m2, p < 0.05) and waist
      circumference (96.7 +/- 16.39 cm vs 89.2 +/- 11.05 cm, p < 0.05). In univariate
      analysis, we did not observe a relation between the presence of a R223 or N656
      genotype and gallstone disease in our population (OR = 0.78, 95% CI 0.35-1.73).
      CONCLUSION: Obesity-related leptin receptor polymorphisms are not associated with
      gallstones disease.

PMID- 16807516
TI  - An experience with covered transjugular intrahepatic portosystemic shunt for
      refractory ascites from western India.
AB  - BACKGROUND: In refractory ascites/hydrothorax (RA), uncovered transjugular
      intrahepatic portosystemic shunt (TIPS) is shown to be superior to large-volume
      therapeutic paracentesis (LVP) for long-term control of ascites, but at a cost of
      increased risk of hepatic encephalopathy (HE). Use of covered TIPS has shown to
      improve shunt patency rate over uncovered TIPS. This retrospective analysis was
      performed on patients with RA to assess efficacy of TIPS, both covered and
      uncovered. METHODS: Over 10-year period, patients with RA, patients either
      required LVP at least 2 times in a month, or were intolerant to LVP, or were
      unwilling to undergo further LVP, were treated with TIPS (Group-A = 12 patients
      with uncovered TIPS {Wallstent = 10, Memotherm = 1, SMART = 1}, age = 56.1 +/-
      4.5 years, male: female = 5:1; Group-B = 11 patients with e-PTFE-covered TIPS
      {Viatorr = 11}, age = 55.8 +/- 5.2 years, male: female = 8:3). They were followed
      up with clinical and ultrasonography/ Doppler examination every monthly for 3
      months and every 3 monthly thereafter (mean = 9.6 +/- 4.2 months). Clinical
      success (disappearance of ascites at 1-month), technical success (post-TIPS
      reduction of portosystemic pressure gradient {PPG} < 12 mmHg), appearance of
      encephalopathy, TIPS-dysfunction (> 50% reduction in flow-velocity, > 50% shunt
      stenosis or increase in PPG > 12 mmHg in presence of symptoms) and mortality were
      noted. Data were analyzed using chi-square test and t test. RESULTS: Baseline
      clinical and biochemical characteristics were similar in both groups. TIPS
      placement was possible in 11/12 group-A and 11/ 11 group-B patients. Fall in PPG
      after TIPS was similar in both groups. One patient in group-A was lost followup
      after the procedure. On comparison of group-A and group-B, clinical success
      (63.3% and 81.8%), technical success (90.9% and 100%), occurrence of HE (60% and
      54.4%) and mortality at 1-year (70% and 63.3%) were not significantly different.
      TIPS-dysfunction requiring re-intervention was significantly more common in group
      A (50%) than group-B (0%). CONCLUSIONS: Covered TIPS was superior to uncovered
      TIPS, because of less TIPS-dysfunction without increasing chances of HE; but
      failed to offer any survival advantage.

PMID- 16807518
TI  - Common bile duct: a retreat for ascariasis!

PMID- 16807517
TI  - Metabolic syndrome, non-alcoholic steatohepatitis (NASH), and hepatocyte growth
      factor (HGF).
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is not only an antiapoptotic and
      antifibrotic factor of liver, but it is also an adipokine. Serum HGF levels are
      strongly associated with liver diseases, obesity, insulin resistance (IR), and
      metabolic syndrome (MS). Non-alcoholic steatohepatitis (NASH) is the hepatic
      component of MS. To the best of our knowledge, serum HGF levels in patients with
      NASH have not been previously studied. Our aim was to elucidate the correlation
      of HGF with the clinical and histopathological parameters of NASH. METHODS: The
      study group consisted of 26 patients (13 men) who had clinical diagnoses of NASH
      and underwent liver biopsies. Controls were 13 volunteers (3 men) with negative
      viral autoimmune markers, and with normal levels of serum lipids and liver
      enzymes. RESULTS: Among the NASH patients, 14(54%) were overweight and 10 (39%)
      had grade I-II obesity. All the patients had class 3-4 non-alcoholic fatty liver
      disease (NAFLD) except for 2 who had class 2 disease. All of the patients had
      Child's class A liver disease, and MS was present in 5 (19%) patients and 8(31%)
      patients had Homeostasis Model Assessment of Insulin Resistance (HOMA) > 3. Serum
      HGF levels were similar in NASH patients (1.24 +/- 1.09 pg/mL) and controls (0.86
      +/- 0.22 pg/mL) (p = 0.21). The levels of serum HGF did not differ between the
      patients with or without MS (1.65 +/- 1.48 pg/mL and 1.04 +/- 0.80 pg/mL,
      respectively, p=0.65). HGF was not correlated with the laboratory or
      histopathological parameters. CONCLUSIONS: Serum HGF levels were higher in NASH
      patients than in the controls, although it was statistically insignificant and a
      correlation with MS could not be detected in this study.

PMID- 16807520
TI  - An unusual cause of bilioenteric anastomotic dysfunction after iatrogenic bile
      duct injury.
AB  - Roux en Y hepatojejunostomy is the surgery of choice for bile duct repair.
      Anastomotical dysfunction after reconstruction has several etiopathologies.
      Besides technical factors, ischemia of the duct is responsible for late
      obstruction. Bile colonization with secondary stones and sludge can also be
      identified as a cause. An unusual cause of anastomotical dysfunction secondary to
      ascaris biliary infestation after biliary reconstruction is reported herein. The
      patient had intermittent cholangitis and eosinophilia. At operation, the worm was
      found obstructing the anastomosis.

PMID- 16807519
TI  - Vanishing bile duct syndrome in a child with toxic epidermal necrolysis: an
      interplay of unbalanced immune regulatory mechanisms.
AB  - Vanishing bile duct syndrome (VBDS) is a rare disorder and requires a liver
      biopsy for a diagnosis. The condition has not been reported in children with
      toxic epidermal necrolysis (TEN). The etiology of VBDS in our patient with TEN is
      most likely from drug hypersensitivity. A high index of suspicion will prompt
      clinicians to start more specific investigations and treatments. The use of
      immunosuppressive agents, intravenous immunoglobulin and ursodeoxycholic acid has
      not been consistently successful in these patients. A new approach with biologic
      agents such as anti-tumor necrosis factor-alpha may be a promising therapy and
      reduce severe adverse outcomes.

PMID- 16807521
TI  - Traumatic dissociation, epileptic-like phenomena, and schizophrenia.
AB  - OBJECTIVES: According to recent evidence, trauma and stress are important
      etiological factors in pathogenesis of schizophrenia. However, the hypothetical
      influence of traumatic stress on epileptic-like (or kindling) phenomena in
      schizophrenia is at this time unclear. METHODS: In order to discover the
      influence of trauma, 82 patients with a diagnosis of paranoid schizophrenia and
      50 healthy controls were assessed for symptoms of dissociation, traumatic stress
      and psycho-sensory symptoms of epileptic origin. RESULTS: We have found
      significant traumatization and dissociation in patients who met the cut-off score
      for psychosensory epileptic-like symptoms and also significant correlations among
      these measures have been found. CONCLUSIONS: These data suggest a certain role of
      epileptic-like phenomena in dissociative states in schizophrenia and are in
      accordance with rare intracranial EEG findings which suggest a certain role of
      epileptiform events in schizophrenia.

PMID- 16807522
TI  - The association of monoamine oxidase B functional polymorphism with postoperative
      pain intensity.
AB  - OBJECTIVES: The monoamine oxidase B (MAO-B) is an enzyme involved in metabolism
      of dopamine, benzylamine, phenylethylamine, tyramine and tryptamine. The A/G
      polymorphism in intron 13 of the MAO-B gene has been previously found to be
      associated with variability of the MAO-B enzyme activity. The aim of the present
      association study has been to examine the relationship between the A/G
      polymorphism in intron 13 and postoperative pain intensity. METHODS: 284 subjects
      (105 males and 179 females) undergoing planned tonsillectomy were examined. The
      intensity of pain was evaluated using 100-mm visual analogue scale (VAS). A PCR
      method with allele specific primers for detection of A/G polymorphism was used.
      RESULTS: We found a relationship between the A/G polymorphism in intron 13 of the
      MAO-B gene and average intensity of postoperative pain in male subjects. Higher
      average intensity of postoperative pain was detected in males with the G allele
      (3.96) in comparison with males with the A allele (3.45) and the difference was
      statistically significant (p<0,03). CONCLUSIONS: Results of this study indicate
      the relationship between the MAO-B polymorphism and postoperative pain intensity
      in the Czech male population. A potential role of MAO-B in the perception of pain
      intensity is discussed.

PMID- 16807523
TI  - Stimulation of the hippocampal glutamate receptor systems induces stress-like
      responses.
AB  - OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis controls glucocorticoid
      secretion and is in turn controlled by a diverse set of afferents in the brain.
      However, the precise mechanisms underlying these actions remain to be elucidated.
      In our previous study, a lesion in the entorhinal cortex, which is the major
      provider of glutamatergic innervation to the hippocampus, significantly
      attenuated the elevation of adrenocorticotropic hormone (ACTH) in plasma during
      immobilization stress. In the present study, we examined the effects of
      microinjections of glutamatergic agonists into the hippocampus on plasma ACTH and
      glucose concentrations. We also studied the interactions between glutamate and
      acetylcholine in this response in the hippocampus. MATERIALS AND METHODS: NMDA
      and AMPA subtypes of glutamate agonists were microinjected into the rat
      hippocampus, and ACTH and glucose levels in plasma were measured. The interaction
      between cholinergic and glutamatergic systems was investigated pharmacologically.
      RESULTS: Both the NMDA and AMPA subtypes of glutamate agonists induced elevations
      of plasma ACTH and glucose levels in a dose-dependent fashion. These responses
      were independent of those induced by activation of the hippocampal cholinergic
      system. CONCLUSION: Stimulation by the NMDA and AMPA subtypes of glutamate
      receptors in the hippocampus induced elevations of plasma ACTH and glucose, and
      these responses were independent of the cholinergic system.

PMID- 16807524
TI  - Gender-dependent differences in sensation seeking and social interaction are
      correlated with saliva testosterone titre in adolescents.
AB  - OBJECTIVES: In the present study, we tested the hypothesis that gender -
      dependent differences in novelty seeking, leadership, and sympathy might
      correlate with testosterone titre. Since several studies report that the impact
      of testosterone on personality traits is more visible under emotional challenging
      situations, we harvested saliva testosterone upon an anticipated stressor
      (academic examination) and under basal conditions. SETTING AND DESIGN: 19 female
      and 23 male adolescents (17 to 19 years of age) completed standardized
      questionnaires on sensation seeking, anxiety, and social interaction. Two weeks
      later, they had to write an anticipated, rigorous examination in mathematics in
      their school. Before and after the examination, saliva had been harvested from
      each subject and testosterone titre has been estimated. METHODS: Saliva
      testosterone was quantified using a luminescence immunoassay (LIA). Each subject
      completed questionnaires on sensations seeking according to Zuckerman (SSS - V),
      anxiety (STAI), and social interactions. RESULTS: Both genders showed an increase
      in their testosterone titre shortly after examination or announcement of test
      scores. A Spearman correlation coefficient indicated a significant correlation
      between testosterone titre and sensation seeking subscales in female but not in
      male subjects. Analysis of social interactions revealed that peers regarded male
      subjects, who had high testosterone titres, as leaders but not as likeable
      individuals, whereas they regarded female subjects, who had high testosterone
      titres, not as leaders but as highly likeable individuals. CONCLUSION: Theses
      findings strongly suggest that testosterone has gender specific effects on
      novelty seeking, dominance, and sympathy.

PMID- 16807525
TI  - CSF-studies in neuropsychiatric disorders.
AB  - Cerebrospinal fluid (CSF) is a clear and colourless fluid that surrounds the
      brain and spine. Due to the close proximity of CSF to the brain, pathological
      brain-processes are likely to be reflected in CSF. CSF can be obtained through
      lumbar puncture and is frequently performed in the differential diagnosis of
      neuropsychiatric disorders. Beyond clinical applications, CSF has been studied as
      part of different research-protocols. In this review, we will focus on CSF
      analysis in Alzheimer Disease, major depression and schizophrenia. We will review
      both clinical applications as well as research applications in all three
      disorders. We will also assess new technological advances that have made it
      possible to study large numbers of proteins in CSF and how these advances may
      change CSF-analysis in the years to come.

PMID- 16807526
TI  - A meta-analysis epidemiological assessment of neurodevelopmental disorders
      following vaccines administered from 1994 through 2000 in the United States.
AB  - BACKGROUND: Thimerosal is an ethylmercury-containing compound (49.6% mercury by
      weight) used as at the preservative level in vaccines (0.005% to 0.01%). METHODS:
      Statistical modeling in a meta-analysis epidemiological assessment of the Vaccine
      Adverse Event Reporting System (VAERS) for neurodevelopment disorders (NDs)
      reported following Diphtheria-Tetanus-whole-cell-Pertussis (DTP) vaccines in
      comparison to Diphtheria-Tetanus-whole-cell-Pertussis-Haemophilus Influenzae Type
      b (DTPH) vaccines (administered: 1994-1997) and following Thimerosal-containing
      Diphtheria-Tetanus-acellular-Pertussis (DTaP), vaccines in comparison to
      Thimerosal-free DTaP vaccines (administered: 1997-2000), was undertaken. RESULTS:
      Significantly increased adjusted (sex, age, vaccine type, vaccine manufacturer)
      risks of autism, speech disorders, mental retardation, personality disorders,
      thinking abnormalities, ataxia, and NDs in general, with minimal systematic error
      or confounding, were associated with TCV exposure. CONCLUSION: It is clear from
      the results of the present epidemiological study and other recently published
      data associating mercury exposure with childhood NDs, additional ND research
      should be undertaken in the context of evaluating mercury-associated exposures,
      especially from Thimerosal-containing vaccines.

PMID- 16807527
TI  - A new model of anterior subcapsular cataract: involvement of TGFbeta/Smad
      signaling.
AB  - PURPOSE: To develop a new animal model of anterior subcapsular cataract formation
      by topical application of alkali to the eye and to examine the role of
      Transforming growth factorbeta/Smad3 (TGFbeta/Smad3) signaling in the formation
      of this cataract model. METHODS: Under anesthesia, one eye of adult Wistar rats
      (n=142) was subjected to alkali burn by topical application of 1 N NaOH. The eye
      was then histologically examined at specific time intervals. Immunohistochemistry
      with a battery of antibodies was carried out to examine the epithelial
      mesenchymal transition (EMT) in lens epithelium. Enzyme immunoassay was employed
      to determine the level of growth factors in aqueous humor and lens tissue. Smad3
      null mice were also used to examine the role of Smad3 signaling in
      cataractogenesis in this model. RESULTS: Two days post-burn of the ocular
      surface, lens epithelium underwent EMT as evidenced by the upregulation of Snail
      and alpha-smooth muscle actin and formed a multilayer of cells beneath the
      capsule. Smad signaling was found to be activated in EMT-type lens cells. The
      majority of myofibroblast-type lens cells expressed proliferative cell nuclear
      antigen (PCNA). The total amount of active TGFbeta2, total TGFbeta2, and
      Fibroblast growth factor 2 (FGF2) increased in the aqueous humor and lens. Loss
      of Smad3 attenuated, but did not completely abolish, EMT in the lens epithelium.
      CONCLUSIONS: Topical alkali treatment of the ocular surface readily induces an
      EMT-type anterior subcapsular cataract. Smad3 signaling is involved, but not
      required, for achievement of EMT in the lens epithelium in this cataract model.

PMID- 16807528
TI  - NADH binding properties of rabbit lens lambda-crystallin.
AB  - PURPOSE: The present investigation aims to evaluate the NADH binding ability of
      lambda-crystallin, a taxon-specific enzyme-crystallin, in the rabbit lens.
      METHODS: A lambda/betaL1-crystallin fraction was separated from the rabbit lens
      soluble fraction by gel filtration and the enzyme-crystallin was partially
      purified by subsequent affinity column chromatography. Analysis of NADH bound to
      the lambda-crystallin preparation was performed using spectrophotometric and
      enzymological methods. Binding of added NADH to the enzyme-crystallin preparation
      was also analyzed using a simple ultrafiltration method, which was theoretically
      equivalent to equilibrium dialysis, to study additional NADH binding to the
      protein. RESULTS: The prepared lambda-crystallin samples clearly exhibited an
      absorption maximum at 340 nm, even though they were thoroughly dialyzed. This was
      due to the presence of nondialyzable NADH bound tightly to the protein. The bound
      NADH was removed by charcoal treatment, and extracted by 0.1% SDS or 70 degrees C
      heat treatment. A dissociation constant (Kd) of less than 5 nM indicated tight
      binding of NADH. The quantity of bound NADH in the 88% purified 33 kDa enzyme
      crystallin was estimated to be 20.5 nmol/mg protein, suggesting a stoichiometry
      of 0.7 mol of the nucleotide/mol of the 33 kDa protein. Additional looser binding
      of added NADH to lambda-crystallin was observed in both the lambda/betaL1
      crystallin fraction (including the full-length 33 kDa protein: 34%; 25-30 kDa
      proteins, most of which might be generated by cleavage of the 33 kDa protein:
      64%) and the partially purified enzyme-crystallin. It was assumed from the
      analysis of binding titration that some (about 30%) of the 33 kDa protein and
      most of the lower molecular weight proteins still possessed the ability to
      loosely bind NADH. Kd values of their lower affinity binding were determined to
      be 2 or 6 microM. CONCLUSIONS: From the present study, we conclude that lambda
      crystallin plays a sufficiently important role as a NADH binding protein to
      maintain high levels of this nucleotide in the rabbit lens.

PMID- 16807529
TI  - The TGFbeta1 gene codon 10 polymorphism contributes to the genetic predisposition
      to high myopia.
AB  - PURPOSE: Transforming growth factor-beta (TGFbeta), a multifunctional growth
      factor that plays a key role in the remodeling of scleral tissue, may be involved
      in the predisposition and pathophysiology of high myopia. Our aim was to examine
      the association between myopia and the polymorphisms within codon 10 of the
      TGFbeta1 gene. METHODS: This was a case control study. The study group contained
      participants who had high myopia and a spherical equivalent greater than -6.00 D.
      The control group was composed of medical students whose spherical equivalent was
      less then -0.5 D. All volunteers in this study were over 16 years old and had
      never undergone ocular surgery. Genotyping was conducted by restriction fragment
      length polymorphism, and the results were compared between myopia patients and
      control subjects. RESULTS: The frequency of the CC genotype in TGFbeta1 codon 10
      differed significantly between patients in the high myopia group (n=201) and
      individuals in the control group (n=86; p<0.001). People with either the CT or TT
      genotype had a lower probability of having high myopia with a spherical
      equivalent greater than -6.00 D than those with the CC genotype. Furthermore,
      there was a higher frequency of the C allele in the high myopia group than with
      the control group (p<0.001, OR=1.83, CI=1.27-2.63). CONCLUSIONS: The frequency of
      the CC homozygote in the high myopia group was much higher than in the control
      group, indicating people with the CC homozygote may be at a higher risk of
      developing high myopia. Varied expression of this gene may contribute to the
      genetic predisposition to high myopia in Chinese Taiwanese.

PMID- 16807530
TI  - Quantitative measurement of young human eye lens crystallins by direct injection
      Fourier transform ion cyclotron resonance mass spectrometry.
AB  - PURPOSE: Human eye lenses at birth are primarily constructed of 12 distinct
      crystallins and two truncated crystallins. The molecular weights of these 14
      proteins vary between about 20,000 and 30,000 Da. The relative amounts of these
      molecules and their post-synthetic changes with age are of substantial interest
      in the study of lens biochemistry and lens pathology. Fourier transform mass
      spectrometry of unfractionated lens homogenates now permits precise quantitative
      measurement of the relative amounts of lens crystallins. We report herein the
      measurement of the 14 crystallins in 10 pairs of lenses from humans between the
      ages of 2 and 300 days. METHODS: Eye lenses were obtained from human donors of
      various ages in the first year of life. These lenses were homogenized in 0.02 M
      phosphate buffer at pH 7.0 with 0.001 M EDTA, desalted by washing over a 3,000 Da
      filter, and injected directly into the nanospray source of a hybrid Fourier
      transform ion cyclotron resonance mass spectrometer, Qq-FT(ICR)MS, equipped with
      a 12 Tesla magnet. The crystallins were quantitatively ionized and mass analyzed
      in the ICR cell of the mass spectrometer. The detected signals of all of the
      isotopic and charge state species for each crystallin were normalized and summed
      to determine the protein quantities. RESULTS: The relative amounts of the 14
      crystallins are found to be quite similar from individual to individual at birth.
      These amounts are in integer ratios to one another that suggest important
      structural relations within the lens. In two cases, the relative amounts of
      alphaA- and betaB2-crystallin change proportionally to the logarithm of age
      during the first year, with alphaA- decreasing and betaB2-crystallin increasing.
      The changes in alphaA- and betaB2-crystallin are mutually offsetting, with alphaA
      crystallin decreasing from 30% to 18% and betaB2-increasing from 12% to 24%.
      CONCLUSIONS: These observations suggest that the human eye lens at birth is
      constructed of crystallins in which the numbers of crystallin molecules have
      regular integral relationships to each other. As the lens develops during the
      first year, some of these relationships change. While the functional significance
      of the reciprocal decrease in alphaA- and increase in betaB2-crystallin is not
      known, betaB2-crystallin may substitute for alphaA-crystallin in the lens
      structures synthesized during the year after birth. Direct injection FT(ICR)MS of
      unfractionated lens was found to be an excellent method for the quantitative
      measurement of lens crystallins.

PMID- 16807531
TI  - Cellular debris and ROS in age-related cortical cataract are caused by
      inappropriate involution of the surface epithelial cells into the lens cortex.
AB  - PURPOSE: To quantify changes in the lens epithelial cells and underlying lens
      cortex responsible for age-related cortical cataract (ARCC) in the rat. METHODS:
      Freshly isolated lenses were stained vitally for DNA with Hoechst 33342. Reactive
      oxygen species (ROS) and mitochondria were visualized and quantified by
      dihydrorhodamine 123 (DHR). The fluorescence was quantified using Laser Scanning
      Confocal Microscopy (LSCM) of vitally stained lenses. Cortical DNA was verified
      as such by DNAse I digestion. Cataract reflections were determined from
      digitalized images of light reflections taken with a low magnification light
      microscope, or with the LSCM. RESULTS: The anterior surface epithelia of old rat
      lenses were full of gaps and ragged in appearance with a decrease of over 50% in
      lens epithelial cell (LEC) density. The surface LECs were frequently seen to have
      involuted into the cortex at inappropriate sites, forming deposits full of DNA,
      nuclear and mitochondrial debris, and abundant ROS. These involutions frequently
      originated near open gaps in the surface epithelia, where they appear to have
      detached from the capsular membrane. Cortical cataracts in the rat lenses were
      seen to co-localize with these LEC involutions, as had been seen previously in
      mice with ARCC. CONCLUSIONS: ARCC in rats co-localized with inappropriate
      accumulations of nuclei, mitochondria, DNA, and expression of ROS in debris
      filled foci. These were the result of both involution of surface LECs into areas
      of cortical ARCC, and by an extension of the normal bow region deep into the
      anterior and posterior of cataractous lenses. These results were in complete
      agreement with our previous studies on ARCC in mice.

PMID- 16807538
TI  - Bone morphogenetic protein-7 expression and activity in the human adult normal
      kidney is predominantly localized to the distal nephron.
AB  - Bone morphogenetic protein-7 (BMP)-7 plays an important role during fetal kidney
      development. In the adult, BMP-7 is most strongly expressed in the kidney
      compared to other organs, but the exact expression pattern as well as the
      function of BMP-7 is unclear. The major aim of the present study was to define
      which parts of the human kidney do physiologically express BMP-7 and which cells
      appear to be targets of BMP activity by showing phosphorylated BMP-receptor
      associated Smads 1, 5, or 8 and inhibitor of differentiation factor 1 (ID1)
      expression. BMP-7 expression was localized by immunohistology to the epithelia of
      the distal tubule as well as the collecting ducts (CDs). Phospho-Smads 1/5/8 and
      ID1 expression largely colocalized with BMP-7 and was also localized in the
      epithelia of the distal tubule and the CDs. This was confirmed by polymerase
      chain reaction-based mRNA expression analysis. In vitro, proximal tubular cells
      (PTCs) expressed BMP receptors and BMP-receptor-associated Smads and were
      reactive to BMP-7. Our data indicate that BMP-7 expression in the adult human
      kidney appears to be more restricted than in the fetal situation and
      predominantly found in the distal nephron. Also, evidence of in vivo BMP
      signalling (i.e. phospho-Smads and ID1 expression) was found there. These
      findings suggest that BMP-7 plays a physiological role mostly in this part of the
      kidney. Still, as reported previously, PTCs are responsive to BMP-7, but
      presumably not in an autocrine or paracrine mode in normal adult kidneys.

PMID- 16807539
TI  - Vascular defect beyond the endothelium in type II diabetic patients with overt
      nephropathy and moderate renal insufficiency.
AB  - There is a paucity of data on the effects of overt nephropathy and moderate renal
      impairment on endothelial function in diabetic patients. A total of 26 type II
      diabetic (DM) patients with nephropathy (DMN+) (mean +/- s.d. age: 63.7 +/- 6.3
      years), 32 diabetic patients without nephropathy (DMN-) (59.4 +/- 10.1 years),
      and 52 non-diabetic subjects (54.9 +/- 8.2 years) were recruited. High-resolution
      ultrasound scan was used to measure carotid intima media thickness (IMT) and flow
      mediated dilation (FMD) of the brachial artery. Endothelium-independent dilation
      was determined by maximal vascular dilation after sublingual nitroglycerine
      (glyceryl trinitrate (GTN)-induced dilation). The mean carotid IMT increased
      progressively from non-DM to DMN- to DMN+ groups (0.74 +/- 0.23 vs 0.80 +/- 0.25
      vs 1.03 +/- 0.38 mm; P=0.001 for trend) whereas FMD- (4.3 +/- 2.5 vs 3.9 +/- 1.7
      vs 1.9 +/- 2.0%, P<0.001 for trend) and GTN-induced dilation (14.7 +/- 4.0 vs
      14.5 +/- 3.9 vs 10.3 +/- 3.2%; P<0.001 for trend) declined in an opposite manner.
      On multivariate analysis, age (beta=0.257, P=0.009), glomerular filtration rate
      (beta=-0.364, P<0.001), and smoking (beta=0.25, P=0.013) were independently
      associated with carotid IMT (F=15.76, R(2)=0.340, P<0.001). After adjustment for
      baseline brachial arterial diameter, history of smoking (beta=-0.039, P<0.001),
      fasting plasma glucose (beta=-0.033, P=0.002), and total cholesterol (beta=
      0.023, P=0.024) were independently associated with vessel diameter after FMD
      (F=2446.5, R(2)=0.992, P<0.001); whereas age (beta=-0.069, P=0.001) and urinary
      albumin excretion (beta=-0.048, P=0.018) were independently associated with
      vessel diameter after GTN (F=851.6, R(2)=0.967, P<0.001). Type II diabetic
      patients with overt nephropathy and moderate renal impairment had both structural
      and functional vascular abnormalities beyond the endothelium.

PMID- 16807540
TI  - Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular
      cell death and crystallization inhibitors.
AB  - We previously reported that oxidative stress and renal tubular damage occur in
      chronic hyperoxaluric rats. However, the in vivo responses of renal epithelial
      cells after vitamin E administration and their correlations with calcium oxalate
      (CaOx) crystal formation have not been evaluated. Male Wistar rats received 0.75%
      ethylene glycol (EG) for 7, 21, or 42 days to induce CaOx deposition (EG group).
      Another group of EG-treated rats received 200 mg kg(-1) of vitamin E
      intraperitoneally (EG+E group) to evaluate its effect on hyperoxaluria. Urinary
      electrolytes and biochemistry and levels of lipid peroxides and enzymes were
      examined, together with serum vitamin E levels. Levels of the tubular markers,
      alpha and mu glutathione S-transferase, proliferating cell nuclear antigen
      (PCNA), osteopontinin (OPN), and Tamm-Horsfall protein (THP) were also measured,
      and TUNEL staining was performed to examine the viability of the tubular
      epithelium. There were no significant differences between the two age-matched
      controls either untreated or given vitamin E. Compared to untreated controls,
      tubular cell death was increased at all time points in EG rats with a gradual
      increase in CaOx crystals, whereas the number of PCNA-positive cells was only
      significantly increased on day 21. In EG+E rats, tubular cell death was decreased
      compared to the EG group, and cell proliferation was seen at all time points,
      while CaOx crystal deposition was decreased, but hyperoxaluria, urinary lipid
      peroxides, and enzymuria were unaffected. Vitamin E supplement prevented the loss
      of OPN and THP in renal tissues by EG and the reduction in their levels in the
      urine. The beneficial effect of vitamin E in reducing CaOx accumulation is due to
      attenuation of tubular cell death and enhancement of the defensive roles of OPN
      and THP.

PMID- 16807541
TI  - Contribution of adenosine receptors in the control of arteriolar tone and
      adenosine-angiotensin II interaction.
AB  - Adenosine (Ado) mediates vasoconstriction via A(1)-Ado receptors and vasodilation
      via A(2)-Ado receptors in the kidney. It interacts with angiotensin II (Ang II),
      which is important for renal hemodynamics and tubuloglomerular feedback (TGF).
      The aim was to investigate the function of Ado receptors in the Ado-Ang II
      interaction in mouse microperfused, afferent arterioles. Ado (10(-11)-10(-4)
      mol/l) caused a biphasic response: arteriolar diameters were reduced (-7%) at Ado
      10(-11)-10(-9) mol/l and returned to control values at higher concentrations.
      Treatment with Ang II (10(-10) mol/l) transformed the response into a
      concentration-dependent constriction. N(6)-cyclopentyladenosine (A(1)-Ado
      receptor agonist) reduced diameters (12% at 10(-6) mol/l). Application of
      CGS21680 (10(-12)-10(-4) mol/l, A(2A) receptor agonist) increased the diameter by
      13%. Pretreatment with ZM241385 (A(2A)-Ado receptor antagonist) alone or in
      combination with MRS1706 (A(2B)-Ado receptor antagonist) resulted in a pure
      constriction upon Ado, whereas 8-cyclopentyltheophylline (CPT) (A(1)-Ado receptor
      antagonist) inhibited the constrictor response. Afferent arterioles of mice
      lacking A(1)-Ado receptor did not show constriction upon Ado. Treatment with Ado
      (10(-8) mol/l) increased the response upon Ang II, which was blocked by CPT. Ado
      (10(-5) mol/l) did not influence the Ang II response, but an additional blockade
      of A(2)-Ado receptors enhanced it. The action of Ado on constrictor A(1)-Ado
      receptors and dilatory A(2)-Ado receptors modulates the interaction with Ang II.
      Both directions of Ado-Ang II interaction, which predominantly leads to an
      amplification of the contractile response, are important for the operation of the
      TGF.

PMID- 16807542
TI  - Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin
      receptor gene-transgenic rats.
AB  - Increased macula densa cyclooxygenase-2 (COX-2) is observed in diabetic rats and
      may contribute to hyperfiltration states. However, the signals mediating
      increased COX-2 expression in diabetic rats remain undetermined. We recently
      found that non-proteolytic activation of prorenin by site-specific binding
      proteins, such as prorenin receptor, plays a pivotal role in the development of
      diabetic nephropathy. The present study was designed to determine the
      contribution of prorenin receptor to renal cortical COX-2 expression. The COX-2
      mRNA and protein levels of six 4-week-old male wild-type rats and six human
      prorenin receptor gene-transgenic (hProRenRcTg) rats were measured by real-time
      polymerase chain reaction methods, Western blotting, and immunohistochemistry,
      and compared. There were no differences between the two groups in arterial
      pressure measured by telemetry, urinary sodium excretion, or renal levels of rat
      prorenin receptor mRNA. The renal cortical COX-2 mRNA levels of the hProRenRcTg
      rats were significantly higher than those of the wild-type rats, and the renal
      cortical COX-2 protein levels were also higher in hProRenRcTg rats than in the
      wild-type rats. Immunohistochemical analysis revealed that COX-2 immunostaining
      was predominantly present in the macula densa cells, and significantly more COX-2
      positive cells were present in the hProRenRcTg rats than in the wild-type rats.
      In addition, COX-2 inhibition with NS398 significantly decreased renal cortical
      blood flow in the hProRenRcTg rats but not in the wild-type rats. These results
      strongly suggest that human prorenin receptor directly or indirectly contributes
      to the regulation of renal cortical COX-2 expression.

PMID- 16807543
TI  - Renal and vascular actions of urotensin II.
AB  - The peptide hormone urotensin II (UII) has been highly conserved through the
      vertebrates from fish to humans. As it was shown to be the endogenous ligand for
      the mammalian orphan G-protein-coupled receptor GPR14, now renamed the UT
      receptor, interest in UII physiology has grown. Initial observations of a potent
      vasoconstrictor effect have been tempered with the subsequent revelation of an
      endothelium-dependent vasodilator action. These complex and contrasting vascular
      actions are both species- and vascular bed-specific. UII also plays a role in
      body fluid regulation in lower vertebrates, and it now appears that this extends
      to mammals. The kidney is a major source of both circulating and urinary UII. UII
      is found in both the proximal tubules and collecting ducts; the UT receptor is
      localized primarily to the renal medulla, with greatest expression in the inner
      medullary collecting ducts. Infusion in rats produced conflicting results:
      exogenous UII has been shown to increase glomerular filtration rate (GFR) and
      excretion of water and sodium, but also to reduce the same variables. Inhibition
      of UT receptor activity with the antagonist urantide resulted in an increase in
      GFR, diuresis, and natriuresis, suggesting that endogenous UII exerts a tonic
      influence on basal renal function. UII may also play a role in renal disease,
      being elevated in the circulation or urine of patients with renal failure and in
      experimental models of cardiovascular disease such as the spontaneously
      hypertensive rat. It remains to be established whether these changes represent an
      underlying primary cause or a compensatory response.

PMID- 16807544
TI  - Honokiol, a small molecular weight natural product, alleviates experimental
      mesangial proliferative glomerulonephritis.
AB  - Glomerulonephritis (GN) is still the most common cause of end-stage renal
      disease. Accumulation of glomerular macrophages, proliferation of mesangial
      cells, and deposition of extracellular matrix proteins are pathobiological
      hallmarks of GN. Pharmacological interventions that can inhibit these insults may
      be beneficial in the retardation of the progression of GN. Honokiol originally
      isolated from Magnolia officinalis, shows antioxidative, anti-inflammatory, and
      antiproliferative activities in a variety of inflammation models. In this study,
      we first investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis.
      Anti-Thy1 nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1
      antibodies intravenously. Nephritic rats were randomly assigned to receive
      honokiol (2.5 mg/kg, twice a day) or vehicle and were killed at various time
      points. Glomerular histology and immunohistopathology and urine protein excretion
      were studied. Western blotting was conducted for markers of proliferation.
      Adhesion molecules, chemokine, and extracellular matrix gene expression were
      evaluated by Northern blotting. Honokiol-treated nephritic rats excreted less
      urinary protein and had lower glomerular cellularity and sclerosis. The increased
      intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in
      nephritic rats could be abolished by the treatment of honokiol. Honokiol also
      alleviated glomerular monocyte chemoattractant protein-1 and intracellular
      adhesion molecule-1, similar to type I (alpha1) collagen and fibronectin mRNA
      levels of nephritic rats. These results indicate that honokiol may have
      therapeutic potential in mesangial proliferative GN.

PMID- 16807548
TI  - Prevalence and risk factor analysis of microalbuminuria in Japanese general
      population: the Takahata study.
AB  - Microalbuminuria, an indicator of glomerular injury, is associated with increased
      risk of progressive renal deterioration, cardiovascular disease, and mortality.
      However, the prevalence of microalbuminuria in Japanese general population is
      less certain. Thus, we examined the prevalence of microalbuminuria and its
      associated risk factors in Japan. Subjects of this cross-sectional study were
      asymptomatic individuals over 40 years in Takahata, Japan. Urine albumin
      creatinine ratio was calculated from a single-spot urine specimen collected in
      the morning. Creatinine clearance (CCr) was obtained by Cockcroft-Gault equation.
      Multivariate logistic regression analysis was used to determine which risk
      factors (i.e., age, hypertension, diabetes, obesity, and salt intake) might
      predict the presence of microalbuminuria. A total of 2321 subjects (mean age, 64
      years; men, 1034; women, 1287) were entered into the final analysis. Among them,
      the prevalence of microalbuminuria, macroalbuminuria, and proteinuria by dipstick
      test (> or = 1+) were 317 (13.7%), 39 (1.7%), and 103 (4.4%), respectively. Age,
      hypertension, and diabetes were independently associated with microalbuminuria in
      men. In addition to the classical risk factors detected in men, estimated 24-h
      urinary sodium excretion and uric acid were also independently associated with
      microalbuminuria in women. Among the 668 subjects with renal insufficiency (CCr
      <60 ml/min/1.73 m(2)), the prevalence of microalbuminuria and macroalbuminuria
      were 119 (17.8%) and 18 (2.7%), respectively. In conclusion, microalbuminuria is
      prevalent across all age groups and is associated with lifestyle-related risk
      factors in Japanese general population. However, there are a substantial number
      of subjects with renal insufficiency accompanying no microalbuminuria.

PMID- 16807546
TI  - Long-term regulation of proximal tubule acid-base transporter abundance by
      angiotensin II.
AB  - In the proximal tubule, angiotensin II (Ang-II) regulates HCO(-)(3) reabsorption
      and H+ secretion by binding the type 1 Ang-II (AT1) receptor, stimulating
      Na(+)/HCO(-)(3) cotransport and Na(+)/H(+) exchange. Studies were carried out to
      determine if long-term changes in Ang-II receptor occupation alter the abundance
      of the basolateral Na(+)/HCO(-)(3) cotransporter (NBC1) or the apical membrane
      type 3 Na(+)/H(+) exchanger (NHE3). In the first set of experiments, rats eating
      a low-sodium diet were infused with the AT1 blocker, candesartan, or vehicle. In
      the second, lisinopril-infused rats were infused with either Ang II or vehicle.
      Transporter abundances were determined in whole kidney homogenates (WKH) and in
      brush border membrane (BBM) preparations by semiquantitative immunoblotting.
      Tissue distribution of transporters was assessed by immunocytochemistry. Blockade
      of the AT1 receptor by candesartan caused decreased abundance of NBC1 in WKH (59
      +/- 9% of control; P<0.05) and Ang-II infusion increased abundance (130 +/- 7% of
      control; P<0.05). Changes in NBC1 in response to candesartan were confirmed
      immunohistochemically. Neither candesartan nor Ang II infusion affected the
      abundance of NHE3 in WKH or cortical homogenates. Candesartan decreased type 2
      sodium-phosphate cotransporter abundance in both WKH (52 +/- 7% of control;
      P<0.05) and BBM (32 +/- 7% of control; P<0.05). Serum bicarbonate was decreased
      by candesartan and increased by Ang-II. Candesartan also decreased urinary
      ammonium excretion (P<0.05). The long-term effects of Ang-II in the proximal
      tubule may be mediated in part by regulation of NBC1 abundance, modifying
      bicarbonate reabsorption.

PMID- 16807549
TI  - 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine
      parathyroid cells.
AB  - Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription
      and block chief cell hyperplasia, making them integral tools in the treatment of
      secondary hyperparathyroidism in patients with chronic kidney disease. Recently,
      human parathyroid glands have been shown to express 25-hydroxyvitamin D 1alpha
      hydroxylase (1alphaOHase), but documentation of the 1alphaOHase activity in
      parathyroid cells and its potential role in activating 25-hydroxyvitamin D(3)
      (25(OH)D(3)) to 1,25-dihydroxyvitamin D(3) (1,25(OH)2D3) have not been reported.
      The relative potencies of 25(OH)D(3) and 1,25(OH)(2)D(3) in reducing PTH
      secretion and mRNA were determined in primary cultures of bovine parathyroid
      cells (bPTC). The effects of blocking 1alphaOHase activity on suppression of PTH
      mRNA and induction of 24-hydroxylase mRNA were examined. Vitamin D receptor (VDR)
      affinities were estimated by intact cell competitive binding assay. Metabolism of
      25(OH)D(3) by bPTC was assessed using a radioimmunoassay that measures all 1
      hydroxylated metabolites of vitamin D. 25(OH)D(3) suppressed PTH secretion and
      mRNA (ED(50)=2 nM), but was several hundred times less potent than
      1,25(OH)(2)D(3). The lower potency of 25(OH)D(3) correlated with its lower VDR
      affinity. bPTCs converted 25(OH)D(3) to 1-hydroxylated metabolites, but the rate
      of conversion was low. Inhibition of 1alphaOHase with the cytochrome P450
      inhibitor clotrimazole did not block 25(OH)D(3)-mediated suppression of PTH.
      Clotrimazole enhanced 24-hydroxylase mRNA induction, presumably by inhibiting
      catabolism of 25(OH)D(3). In conclusion, 25(OH)D(3) suppresses PTH synthesis by
      parathyroid cells, possibly by direct activation of the VDR.

PMID- 16807550
TI  - Endothelial bound lipoprotein lipase (LpL) depletion in hypoalbuminemia results
      from decreased endothelial binding, not decreased secretion.
AB  - Hypertriglyceridemia in nephrotic (NS) and Nagase analbuminemic rats (Analb)
      results from reduced triglyceride clearance. NS and Analb have reduced or absent
      albumin, reduced plasma oncotic pressure (pi), but Analb lack proteinuria. The
      heparin releasable lipoprotein lipase (LpL) pool in both models is greatly
      reduced, suggesting reduced LpL is related to low albumin or pi and not
      proteinuria. To determine the cause of endothelial LpL reduction, we studied
      effectors of endothelial LpL (eLpL) levels from gene expression, to delivery and
      endothelial binding. eLpL was measured as heparin releasable activity. eLpL and
      secretion rate was measured in isolated hearts perfused with heparin. mRNA levels
      were measured in rat hearts by kinetic RT-PCR. Finally, binding of (125)I-LpL by
      competition assays rat endothelial cells measured serum-induced changes in
      affinity. eLpL in vivo was reduced in nephrotic and Analb rats. While the eLpL
      pool was reduced in isolated perfused hearts, neither LpL secretion by isolated
      hearts nor myocardial mRNA was reduced in NS or Analb. Binding of LpL to RAEC
      preincubated with serum from either NS or Analb was reduced compared to control.
      LpL mRNA levels and release rate was not altered in hearts from NS rats, while
      eLpL is depleted, suggesting that reduced eLpL in NS is not the result of reduced
      delivery. The finding that NS serum alters LpL binding to RAEC suggests LpL
      depletion results from decreased binding rather than defective delivery. This in
      turn is a consequence of reduced serum albumin or pi but does not require
      proteinuria.

PMID- 16807558
TI  - How do you categorize an animal's natural life span? 100% E.

PMID- 16807559
TI  - How do you categorize an animal's natural life span?

PMID- 16807560
TI  - How do you categorize an animal's natural life span? Natural does not equal pain
      free.

PMID- 16807561
TI  - Liver lesion in an opossum (Didelphus virginianus). Diagnosis: incidental
      iatrogenic foreign body (gossypiboma).

PMID- 16807563
TI  - Air sac cannula placement in birds.
AB  - Air sac cannulas are indicated in birds with upper respiratory obstruction or for
      ventilation during surgical procedures involving the head and neck. Proper
      technique, knowledge of potential complications, and an understanding of the
      indications for air sac tube placement are important for scientists,
      veterinarians, and technicians who work with birds.

PMID- 16807565
TI  - Barriers to assessment and treatment of pain in laboratory animals.
AB  - Pain is an undesirable potential consequence of many of the procedures conducted
      on animals in the course of scientific research, and in most cases it is
      unnecessary. The US Congress, the public, and laboratory animal medical
      professionals have indicated that pain should be prevented or minimized in
      laboratory animals, yet there is ample evidence to suggest that unalleviated pain
      is still a problem for some laboratory animals. This evidence is circumstantial
      to some extent but has its basis in problematic issues of pain control in both
      veterinary and human medicine. The author attempts to identify specific barriers
      to reduction of pain in laboratory animals. She then seeks to determine the
      relative importance of each obstacle and to develop approaches to overcoming each
      obstacle.

PMID- 16807564
TI  - Detection, eradication, and research implications of Helicobacter infections in
      laboratory rodents.
AB  - Researchers first isolated and characterized Helicobacter hepaticus in 1994 as a
      cause of hepatitis that progressed to hepatocellular carcinoma in A/JCr mice.
      During the past decade, isolation and characterization of additional novel
      helicobacters from rodents has continued. In addition to causing overt disease,
      rodent helicobacter infections are important because intercurrent disease in
      select models will confound research data. Emerging evidence suggests that
      inflammatory responses to enterohepatic helicobacter infections may alter host
      responses to other experimental stimuli in unanticipated ways. Additionally,
      scientists have experimentally infected a variety of inbred mouse strains and
      genetically engineered mice with a variety of Helicobacter spp. isolated from
      rodents, birds, and higher mammals (including humans) to develop animal models of
      gastrointestinal diseases as well as idiopathic human disease syndromes. This
      review highlights current information about helicobacter infections in laboratory
      rodents and provides recommendations for the detection and eradication of these
      infections. The authors discuss the impact of subclinical and clinical disease
      and offer recommendations for managing helicobacter-free rodent colonies.

PMID- 16807566
TI  - Use of an adjustable restraint device for prolonged and intermittent intravenous
      infusion and blood sampling in ferrets.

PMID- 16807568
TI  - The Community-Referred Radiology scheme: an evaluation.
AB  - AIMS: To evaluate the Community-Referred Radiology (CRR) scheme. METHODS: The
      study involved: (1) interviews with local stakeholders; (2) analysis of the
      number, type, and cost of referrals as well as sociodemographic characteristics
      of patients using the CRR database (for the year October 2003-October 2004); and
      (3) review of referral criteria, by an independent radiologist, of a random
      sample of 100 referrals. RESULTS: The scheme was widely used, and was viewed as
      being highly satisfactory by general practitioners. There were 117 types of
      radiology investigation ordered. Chest X-ray was the most requested
      investigation. Women constituted 65.5% of users. Maori had a lower rate of
      referral compared with New Zealand (NZ) European. The average cost of
      investigation in the NZ European and the 'Not stated' groups was higher than in
      other ethnic groups. Six (6.1%) of referrals did not align with the National
      Radiology Referral Guidelines. CONCLUSIONS: The CRR scheme is perceived as being
      a popular, well-run, and streamlined service. The comparatively low rate of
      radiology referral for Maori people and people living in the most deprived areas
      as well as the lower average cost of their tests warrant further investigation. A
      number of recommendations are made aimed at further enhancing the scheme.

PMID- 16807570
TI  - Patients' complaints about doctors in surgical training.
AB  - AIM: Research looking at the effect of complaints on senior medical staff has
      shown that while there is important information to be gained from patient
      criticisms of medical care, they are often not well received by doctors. There is
      no information on the effects of complaints on junior medical staff and those
      undergoing vocational training in New Zealand. The aim of this study is to assess
      the impact of complaints on trainees in general surgery. METHOD: A questionnaire
      was devised and sent to all advanced general surgical trainees in New Zealand.
      There were four sections to the questionnaire covering background, professional
      life, family life, and personal health. The scale was semantically anchored at
      not applicable, strongly agree, agree, neither, disagree, and strongly disagree.
      RESULTS: Following electronic mailings of the questionnaire at three different
      times, 35 of 58 (60%) questionnaires were returned of which 21 (60%) of the
      respondents had received at least one major complaint; 10 (29%) indicated they
      had experienced one complaint; 4 (11%) reported 2 complaints; 3 (9%) had received
      3 complaints; and 1 (3%) reported 4 complaints. None of the respondents believed
      that the complaint had improved their surgical training. Thirty-one (86%)
      respondents believed that the complaint had made them practice more defensively;
      13 (38%) felt that the complaint had a negative effect of future doctor-patient
      relationships; and 15 (43%) felt a lack of trust with such relationships. Twenty
      three (67%) felt decreased enjoyment with their training and 18 (53%) felt the
      complaint had a negative effect on their family. Twenty-seven (78%) felt
      depressed over the complaint, with 18 (52%) feeling a lack of support and being
      alone with the experience. CONCLUSION: Trainees receiving complaints find them
      difficult to deal with; they incur an emotional cost on the doctor and possible
      future doctor patient relationships. Thus it is important that trainee doctors
      receive support and guidance throughout this difficult and stressful event.

PMID- 16807569
TI  - The New Zealand mobile surgical bus service: what is it achieving?
AB  - AIM: Equitable access and provision of healthcare is a cornerstone of New Zealand
      Government health planning. Recent closures of rural hospitals have lead to
      difficulties with access to surgical services. The mobile surgical service has
      been developed to help; partly to address this issue as well as to address
      several other stated goals in the provision of rural heath. This study aims to
      audit the goals set out for the mobile surgical service and determine if they are
      been achieved. METHOD: The following outcome measures were assessed: number and
      type of procedure, length of stay, complications, services for Maori, upskilling
      for rural staff, social benefits, impact on child health, improved training with
      telepresence surgery, and the cost. RESULTS: Over the first 2 years (1 March 2002
      to 28 February 2004) of service provision, 1901 procedures were undertaken; 57
      patients had complications. The most common complication was wound infection,
      which occurred in 5% of operations. One in 3 treated patients were Maori and 40%
      of those treated were 15 years of age or younger. The mobile surgical bus service
      also appears to be meeting its social benefit, upskilling goals, and educational
      goals. CONCLUSIONS: The provision of specialist services to the rural communities
      is a difficult problem faced not only in New Zealand. Though still on a trial
      basis, the mobile surgical service bus appears to be meeting its stated goals to
      be addressing one of the important goals of the Government health policy:
      equitable access and provision to surgical care.

PMID- 16807571
TI  - International medical graduates' training needs: perceptions of New Zealand
      hospital staff.
AB  - OBJECTIVE: To determine the opinion of New Zealand doctors and nurses on the
      possible training needs of international medical graduates (IMGS) in New Zealand
      hospitals. DESIGN: A postal questionnaire sent to hospital doctors and nurses.
      METHODS: All doctors working at Wellington, Kenepuru, and Hutt Hospitals in the
      greater Wellington region, and nurses working in acute medical wards at the same
      hospitals, were asked to complete a questionnaire based on the Northern Clinical
      Training Network and Capital Coast District Health Board resident medical officer
      assessment forms regarding an overseas-trained doctor they had worked with in the
      last year. RESULTS: The response rate for the doctor's questionnaires was 68/174
      (39.1%), with 51 of these from New Zealand doctors rating an international
      medical graduate. The response rate for the nurses was 58/60 (96.7%). Areas where
      the median score of the questionnaire was unsatisfactory (less than three out of
      five on an ordinal scale rating performance) were clinical documentation;
      communication with patients, families, and other health professionals; knowledge
      of hospital policies and procedures, and medicolegal matters; and some aspects of
      patient management. There was no difference in median ratings between doctors and
      nurses. CONCLUSIONS: More specific training may improve the performance of
      overseas-trained doctors in the New Zealand health system. A further study of the
      perceived needs of the overseas-trained doctors themselves may be useful.

PMID- 16807572
TI  - Avoidable hospitalisations: potential for primary and public health initiatives
      in Canterbury, New Zealand.
AB  - AIM: To investigate the extent of potentially "avoidable hospitalisations" in the
      Canterbury District Health Board area; specifically, to identify the leading
      causes, recent trends, and estimated costs of avoidable hospitalisations.
      METHODS: All hospitalisations in Christchurch Hospital from 2000 to 2004 were
      analysed and potentially "avoidable admissions" were categorised using ICD10
      clinical codes. Costs of these admissions were estimated for the financial year
      ending 30 June 2003 using diagnostic-related groups (DRGs). RESULTS: The leading
      causes of potentially "avoidable hospitalisations" in Christchurch Hospital were
      cardiovascular disease, stroke, respiratory, gastrointestinal, and urinary
      disorders. The total estimated costs of avoidable hospitalisations in 2003 were
      NZ 96.6 million dollars, accounting for an estimated 94,462 bed days. The
      estimated costs of cardiovascular admissions (excluding stroke) were 50.6 million
      dollars, with stroke accounting for an additional 6.2 million dollars.
      CONCLUSION: Potentially "avoidable admissions" to Christchurch Hospital comprised
      31% of all hospital admissions. There is considerable opportunity to invest in
      public and primary health initiatives aimed at early detection and intervention,
      with the major opportunities being identified as cardiovascular disease, stroke,
      respiratory, gastrointestinal, and urinary disorders.

PMID- 16807573
TI  - Otago rural hospitals study: what do utilisation rates tell us about the
      performance of New Zealand rural hospitals?
AB  - AIM: To provide a description of the role and function of Otago Province's three
      main rural hospitals, utilising analysis of hospital discharge data for the
      period July 2001 to June 2002. METHODS: Calculation of hospitalisation rates
      based on analysis of information contained in the National Minimum Dataset
      (Hospital Events); Census data from Statistics New Zealand; and local knowledge
      of hospital utilisation by geographical district. RESULTS: A comparison between
      the rural Otago population and New Zealand (as a whole) show age-standardised
      hospitalisation rates of 19,847 vs 19,930 per 100,000, and a mean length of
      hospital stay of 4.5 days vs 6.8 days respectively. Patients aged over 75 years
      account for 49% of the work of rural Otago hospitals calculated by total bed
      days; 9% of patients account for 28% of the total discharges. CONCLUSIONS:
      Results show that Otago's rural hospitals (when compared to the New Zealand
      average) provide an efficient and appropriate service for their communities when
      judged by hospitalisation rates, mean length of stay, and patient groups cared
      for. There are serious difficulties encountered in using the National Minimum
      Dataset to analyse the workload of a rural hospital. An agreed methodology to
      overcome these difficulties is needed as they have significant implications for
      service planning and resource allocation for rural hospitals in New Zealand.

PMID- 16807574
TI  - Medical image. Seminoma with extensive metastases to the right atrium.

PMID- 16807575
TI  - An unusual cause of stroke.

PMID- 16807576
TI  - PHARMAC and the statin debacle.
AB  - Statins are lipid-modifying drugs which dramatically lower the total and low
      density lipoprotein cholesterol levels and have been shown in large clinical
      trials to reduce the rate of vascular events, including heart attacks, strokes,
      and death. For every 1% reduction in the LDL cholesterol level, the relative risk
      for major coronary heart disease events is reduced by approximately 1%. Since the
      landmark Scandinavian Simvastatin Survival Study (4S) was published in 1994,
      multiple further clinical trials have reinforced the benefits of treating large
      numbers of patients with statins with the emphasis on achieving low LDL
      cholesterol levels (currently 1.6 mmol/L) for the optimal management of patients
      at very high risk. However PHARMAC's actions since statins were first available
      have significantly impaired the optimal management of New Zealand patients. A
      review of the methods employed during the statin era is a useful exercise in
      understanding how PHARMAC functions and emphasises the point that rather than
      achieving low-cost prices for drugs, PHARMAC simply impedes the timely delivery
      of modern medicines to New Zealand patients.

PMID- 16807577
TI  - An unusual manifestation of Meckel's diverticulum: strangulated paraumbilical
      hernia.

PMID- 16807578
TI  - Evolution of the New Zealand childhood immunisation schedule from 1980: a
      personal view.
AB  - A personal view of the evolution of the New Zealand immunisation schedule (from
      the perspective of someone who has been involved in the decision-making process
      since 1980) is presented in this article. The rationale behind changes to
      vaccination strategies to control pertussis, hepatitis B, polio, measles, mumps
      and rubella, and Haemophilus influenzae type b are presented. Finally brief
      comment is made on the National Immunisation Register and the likely vaccines to
      be introduced into the schedule in the foreseeable future.

PMID- 16807579
TI  - Is it ethical for doctors to strike?

PMID- 16807580
TI  - PHARMAC and EpiPen for anaphylaxis.

PMID- 16807581
TI  - PHARMAC and erythropoietin for cancer patients.

PMID- 16807582
TI  - More from PHARMAC on long-acting insulin analogues: insulin glargine now funded.

PMID- 16807583
TI  - Criticism of New Zealand Medical Association's position on the minimum purchase
      age for alcohol--and NZMA response.

PMID- 16807584
TI  - Enhanced R-matrix algorithms for multilayered diffraction gratings.
AB  - I present enhanced R-matrix algorithms for analysis of general multilayered
      diffraction gratings. The previous R-matrix algorithms are enhanced in three
      aspects: computational efficiency, numerical stability, and application of half R
      matrix in addition to full and quarter R-matrix recursions. On the basis of the
      eigensolutions of rigorous coupled-wave analysis, the enhanced R-matrix
      algorithms deal with eigen-submatrices directly and bypass the auxiliary layer R
      matrix. Such exclusion of a layer matrix leads to improvements in efficiency and
      algorithm robustness particularly for zero or small layer thickness relative to
      wavelength. Application of the enhanced algorithms to grating diffraction is
      exploited especially for the half and quarter R-matrix recursions. Comparison of
      various R-matrix algorithms via a table of flop counts shows that the enhanced
      algorithms are more efficient apart from being well conditioned.

PMID- 16807586
TI  - Surface contouring by optical edge projection based on a continuous wavelet
      transform.
AB  - A novel optical edge projection method for surface contouring of an object with
      low reflectivity is presented. A structured light edge is projected onto a dark
      surface, and the image is captured by a CCD camera. The surface profile of the
      object is then evaluated by an active triangular projection technique, and a
      whole-field three-dimensional contour of the object is obtained by scanning the
      optical edge over the entire object surface. An edge detection method based on a
      continuous wavelet transform (CWT) is employed to determine the location of the
      optical edge. The method of optical edge detection is described, and
      characteristic details of gray-level distribution along the edge are analyzed. It
      is shown that the proposed wavelet edge detection method is not dependent on any
      threshold values; hence the true edge position can be determined without
      subjective selection. A black low-reflectivity object surface made from woven
      carbon fiber is measured, and the experimental results show that the profile of a
      woven carbon fiber can be obtained by the proposed method.

PMID- 16807585
TI  - Simultaneous measurement of stress and temperature with a fiber Bragg grating
      based on a loop thin-wall section beam.
AB  - We designed and demonstrated what we believe to be a novel sensor for
      simultaneous measurement of stress and temperature. A fiber Bragg grating is
      flatly adhered to the surface of a loop thin-wall section beam. The theoretical
      analyses and the experimental results show that both the central wavelength shift
      and the chirped bandwidth of the grating reflection spectrum have a linear
      relationship with the stress and the temperature, respectively, and the slopes of
      them are different. Therefore, the temperature and stress can be discriminated by
      interrogating the chirped fiber grating. Moreover, we also investigated the
      strain of the loop thin-wall section beam, and the results show that the strain
      is cosine proportional to the double positional angle.

PMID- 16807587
TI  - Linear displacement measurement with a grating and speckle pattern illumination.
AB  - We present a study of the variations of a speckle pattern passing through a
      grating that can be displaced. This study is described theoretically by a simple
      model based on the scalar diffraction theory in the Fresnel zone. The intensity
      correlation of the modified speckle as a function of the grating displacement is
      obtained and compared with experimental results. The possibilities of
      metrological applications in optical encoders are suggested.

PMID- 16807588
TI  - Quantitative rainbow schlieren deflectometry as a temperature diagnostic for
      nonsooting spherical flames.
AB  - Numerical analysis and experimental results are presented to define a method for
      quantitatively measuring the temperature distribution of a spherical diffusion
      flame using rainbow schlieren deflectometry in microgravity. The method employed
      illustrates the necessary steps for the preliminary design of a rainbow schlieren
      system. The largest deflection for the normal gravity flame considered in this
      paper is 7.4 x 10(-4) rad, which can be accurately measured with 2 m focal-length
      collimating and decollimating optics. The experimental uncertainty of deflection
      is less than 5 x 10-(5) rad.

PMID- 16807589
TI  - Surface roughness of stainless-steel mirrors for focusing soft x rays.
AB  - We have used polished stainless steel as a mirror substrate to provide focusing
      of soft x rays in grazing-incidence reflection. The critical issue of the quality
      of the steel surface, polished and coated with gold, is discussed in detail. A
      comparison is made to a polished, gold-coated, electroless nickel surface, which
      provides a smoother finish. We used the surface height distributions, measured
      with an interferometric microscope and complemented by atomic-force microscope
      measurements, to compute power spectral densities and then to evaluate the
      surface roughness. The effects of roughness in reducing the specular reflectivity
      were verified by soft-x-ray measurements.

PMID- 16807590
TI  - Replicated, high-aspect-ratio micro-optical components fabricated from inorganic
      solgel materials.
AB  - A replication process for the fabrication of refractive microlenses from a purely
      inorganic solgel material based on tetraethoxysilane is presented. The
      geometrical dimensions and optical properties of the inorganic microlenses are
      characterized and compared with those of microlenses replicated in a hybrid
      xerogel containing organic additives. By a reduced solvent content in the sol
      composition, together with modifications in the replication process, it was
      possible to obtain inorganic xerogel lenses with exceptionally high sagittal
      height values of as much as 28 microm. Compared with the hybrid xerogel, the
      inorganic xerogel has the advantage of an absorption coefficient that is five
      times lower in the visible spectral range and exhibits optical transparency in
      the near-ultraviolet range for wavelengths down to 200 nm.

PMID- 16807591
TI  - Wavelet-modified maximum average correlation height filter for rotation
      invariance that uses chirp encoding in a hybrid digital-optical correlator.
AB  - We discuss and implement a wavelet-modified maximum average correlation height
      (MACH) filter for 0 degrees -360 degrees in-plane rotations in a hybrid digital
      optical correlator. Use of a wavelet transform improves the performance of the
      MACH filter by reducing the number of filters that are required to identify a
      target rotated at any angle between 0 degrees and 360 degrees in-plane rotations
      and enhances the autocorrelation peak intensity significantly. The output of a
      hybrid digital-optical correlator contains two autocorrelation peaks and a strong
      dc. Using a chirp function with the wavelet-modified MACH filter, the correlation
      signals are focused in three different planes. Thus placing a peak-capturing CCD
      camera at a particular plane, only one autocorrelation peak is recorded,
      discarding the strong dc and other autocorrelation peaks. A signal-to-noise ratio
      has been calculated as a metric of goodness of the proposed wavelet-modified MACH
      filter.

PMID- 16807592
TI  - Programmable polarization-independent spectral phase compensation and pulse
      shaping by use of a single-layer liquid-crystal modulator.
AB  - What we believe to be the first use of a single-layer liquid-crystal modulator
      array for spectral phase pulse shaping that operates independently of input
      polarization is reported. Polarization insensitivity is essential to optical
      fiber-based applications such as dispersion compensation.

PMID- 16807593
TI  - Implementation of discrete unitary transformations by multimode waveguide
      holograms.
AB  - Integration of holograms into multimode waveguides allows the implementation of
      arbitrary unitary mode transformations and unitary matrix-vector multiplication.
      Theoretical analysis is used to justify a design approach to implement specific
      functions in these devices. Based on this approach, a compact mode-order
      converter, a Hadamard transformer, and a spatial pattern generator-correlator are
      proposed and analyzed. Beam propagation simulations are used to verify the
      theoretical calculations and to address bandwidth, scalability, and fabrication
      criteria. Optical pattern generators were successfully fabricated using standard
      photolithographic techniques to demonstrate the feasibility of the devices.

PMID- 16807594
TI  - Phase-shifting digital holography with a phase difference between orthogonal
      polarizations.
AB  - Phase-shifting digital holography with a phase difference between orthogonal
      polarizations is proposed. The use of orthogonal polarizations can make it
      possible to record two phase-shifted holograms simultaneously. By combining the
      holograms with the distributions of a reference wave and an object wave, the
      complex field of the object's wavefront can be obtained. Preliminary experimental
      results are shown to confirm the proposed method.

PMID- 16807595
TI  - Use of polarimetric lidar for the study of oriented ice plates in clouds.
AB  - A polarization lidar operating at 532 nm was converted into an automatic,
      polarimetric lidar capable of measuring the entire Stokes vector of backscattered
      light and its derived quantities. Among these quantities, circular and linear
      depolarizations were studied as tools for investigating the presence of
      anisotropic scattering media. Isotropic scatterers show a simple relationship
      between linear and circular depolarization, a relation that we confirm
      theoretically and experimentally. Deviations from this relation, which are
      possible in the presence of anisotropic scatterers such as horizontally oriented
      ice plates when they are observed with a slant lidar, were studied both
      numerically and experimentally.

PMID- 16807596
TI  - Hot-air optical turbulence generator for the testing of adaptive optics systems:
      principles and characterization.
AB  - A statistically repeatable, hot-air optical turbulence generator, based on the
      forced mixing of two air flows with different temperatures, is described.
      Characterization results show that it is possible to generate any turbulence
      strength up to CN2 Dh approximately 6 x 10(-10) m1/3, allowing a ratio of beam
      diameter to Fried's parameter as large as D/r0 approximately 25 for one crossing
      through the turbulator or D/r0 approximately 38 for two crossings. The outer
      scale (L0 approximately 133 +/- 60 mm) is found to be compatible with the
      turbulator mixing chamber size (170 mm), and the inner scale (l0 approximately
      7.6 +/- 3.8 mm) is compatible with the values in the literature for the free
      atmosphere. The temporal power spectrum analysis of the centroid of the focused
      image shows good agreement with Kolmogorov's theory. Therefore the device can be
      used with confidence to emulate realistic turbulence in a controlled manner. A
      calibrated CN2 profile, both in layer altitude and strength, is necessary for the
      testing of off-axis adaptive optics correction (multiconjugate adaptive optics).
      Testing was done to calibrate the CN2 profile using the slope detection and
      ranging technique. The first results, with only one layer, show the validity of
      the approach and indicate that a multiple-pass scheme is viable with a few
      modifications of the current setup.

PMID- 16807597
TI  - Complementary study of differential absorption lidar optimization in direct and
      heterodyne detections.
AB  - A detailed study using both analytical and numerical calculations of direct and
      heterodyne differential absorption lidar (DIAL) techniques is conducted to
      complement previous studies. The DIAL measurement errors depend on key
      experimental parameters, some of which can be adjusted to minimize the
      statistical error. Accordingly, the pertinent criteria on optical thickness, the
      number of photons emitted at the on and off wavelengths, are discussed to reduce
      the relative error on the total column content or range-resolved measurements
      that rely on either hard target or atmospheric backscatter returns. In direct
      detection, the optimal optical thickness decreases from 1.3 to 0.8 when the
      background increases while the on-line-to-off-line optimal energy ratio decreases
      from 3.6 to 2.7. In heterodyne detection, the minimum error is obtained for an
      optical thickness of 1.2 and an energy ratio of 4.3.

PMID- 16807599
TI  - Doppler-free spectroscopy using a continuous-wave optical frequency synthesizer.
AB  - A continuous-wave (cw) optical frequency synthesizer is demonstrated by using a
      monolithic-type cw optical parametric oscillator (cw-OPO) and an optical
      frequency comb. The cw-OPO is phase locked to an optical frequency comb that is
      phase locked to an atomic clock. The output frequency of the cw-OPO is frequency
      shifted with an electro-optic modulator, which makes it possible to tune the
      frequency continuously over 10 GHz. Furthermore, Doppler-free spectroscopy is
      performed using the optical frequency synthesizer for a cesium D1 line at 895 nm.
      The observed linewidth of 5 MHz is the natural linewidth of cesium. The center
      frequency of the line is consistent with a previous report.

PMID- 16807600
TI  - Laser triangulation for liquid film thickness measurements through multiple
      interfaces.
AB  - Laser triangulation is used to measure the thickness of a liquid film in a test
      section consisting of a quartz viewing window, a water layer, and a hydrophobic
      membrane. The triangulation sensor acquires measurements to the bounding surfaces
      of the film while peering through multiple interfaces. This allows the difference
      between the two measurements to constitute the local film thickness. A refraction
      model is developed and applied to the analysis of data collected from the
      experiment. For verification, an empirical method is also developed and compared
      to the analytical approach. The measurement technique is intended to assess the
      stability of liquid films for use as gas-liquid contactors.

PMID- 16807601
TI  - Narrowband Bragg reflectors in Ti:LiNbO3 optical waveguides.
AB  - Bragg grating reflectors etched in amorphous silicon overlay films have been
      integrated with Ti:LiNbO3 optical waveguides to obtain a narrow (0.05 nm)
      reflectance spectrum with a > 20 dB dip in the transmittance spectrum. These
      results were realized at a wavelength of 1542.7 nm for TE polarization on an x
      cut, y-propagating substrate with gratings etched to a depth of approximately 93
      nm in a 105 nm thick silicon film over a length of 12.5 mm. The reflectance in
      the channel waveguides is found to be strongly dependent on the depth of the
      etched grating. The effect of the Bragg waveguide loss factor on the
      transmittance and reflectance spectra is investigated by using a model for
      contradirectional coupling that includes an attenuation coefficient. The values
      for coupling constants kappa and amplitude attenuation constants alpha of samples
      etched for different time durations to control the grating depths are obtained
      from the model through the use of the depth of the dips in the transmittance
      spectra and the spectral widths of the reflectance peaks. It is concluded that
      the corrugated Si overlay film increases the insertion loss by approximately 2.7
      dB, and the loss is not significantly affected by the grating depth.

PMID- 16807602
TI  - Multimode interference devices with input-output ports on the sides.
AB  - Multimode interference (MMI) devices are useful for power splitting and for the
      separation or combination of wavelengths or polarizations, usually in integrated
      optics. Input-output guides connect to the MMI region by ports. In all previously
      reported MMI devices, the input and output guides connect only to the ends of the
      MMI region; i.e., they are end ported. What is believed to be a novel arrangement
      of the input-output ports on MMI devices is described. By placing input-output
      ports either partially or entirely on the sides of the MMI region (i.e., side
      porting), a variety of benefits are achieved and a variety of new devices can be
      made.

PMID- 16807603
TI  - Characteristic analysis of nanosilicon rectangular waveguides for planar light
      wave circuits of high integration.
AB  - When a full-vectorial finite-difference method is used, rectangular Si waveguides
      can be characterized for planar light-wave circuits of high integration. The
      single-mode condition for a rectangular Si waveguide is obtained first. The
      birefringence, which can be adjusted by modifying the thickness of the cladding
      layer, is also studied. For a nano-Si rectangular waveguide the pure bending loss
      is very small even for an ultrasmall bending radius (e.g., a few micrometers),
      and the transition loss becomes dominant. The width and height are optimized to
      minimize the bending radius for the requirement that the bending loss is smaller
      than 0.1 dB. Finally the coupling between two parallel straight waveguides is
      analyzed, and it is shown that there is an optimal width for the maximal coupling
      length.

PMID- 16807604
TI  - Saturable-absorber-based spatial filtering of high-power laser beams.
AB  - A saturable-absorber-based technique for spatial filtering of high-average-power
      laser beams is described. For a focused, radially symmetric beam having its
      highest intensity at the center, this saturable absorber behaves like a soft
      aperture with gradually increasing attenuation toward the beam edges, thus
      selectively transmitting the low divergence components that are confined close to
      the central axis of the propagating laser beam. This technique has been
      successfully used to reduce the divergence of a high-power, high-repetition-rate,
      tunable, narrowband, pulsed dye laser. Our results demonstrate how a judicious
      choice of operating parameters allows spatial filtering to be achieved with the
      introduction of a minimum absorption loss of the laser beam in the saturable
      absorber. Following a time-dependent analysis of a rate equation model describing
      the propagation and interaction of the laser beam with the saturable absorber, we
      have also obtained theoretical estimates for the extent of spatial filtering. Our
      theoretical estimates have been found to be in good agreement with our
      experimental observations.

PMID- 16807605
TI  - Single-frequency Sb-based distributed-feedback lasers emitting at 2.3 microm
      above room temperature for application in tunable diode laser absorption
      spectroscopy.
AB  - GaInAsSb/GaAlAsSb/GaSb distributed-feedback (DFB) laser diodes based on a type I
      active region were fabricated by molecular beam epitaxy at the Centre
      d'Electronique et de Micro-Optoelectronique de Montpellier (CEM2). The DFB
      processing was done by Nanoplus Nanosystems and Technologies GmbH. The devices
      work in the continuous-wave regime above room temperature around an emission
      wavelength of 2.3 microm with a side-mode suppression ratio greater than 25 dB
      and as great as 10 mW of output power. The laser devices are fully characterized
      in terms of optical and electrical properties. Their tuning properties made them
      adaptable to tunable diode laser absorption spectroscopy because they exhibit
      more than 220 GHz of continuous tuning by temperature or current. The direct
      absorption of CH4 is demonstrated to be possible with high spectral selectivity.

PMID- 16807606
TI  - Ammonia detection by using quantum-cascade laser photoacoustic spectroscopy.
AB  - A pulsed quantum-cascade distributed-feedback laser, temperature tunable from -41
      degrees C to +31.6 degrees C, and a resonant differential photoacoustic detector
      are used to measure trace-gas concentrations to as low as 66 parts per 10(9) by
      volume (ppbv) ammonia at a low laser power of 2 mW. Good agreement between the
      experimental spectrum and the simulated HITRAN spectrum of NH3 is found in the
      spectral range between 1046 and 1052 cm(-1). A detection limit of 30 ppbv ammonia
      at a signal-to-noise ratio of 1 was obtained with the quantum-cascade laser (QCL)
      photoacoustic (PA) setup. Concentration changes of approximately 50 ppbv were
      detectable with this compact and versatile QCL-based PA detection system. The
      performance of the PA detector, characterized by the product of the incident
      laser power and the minimum detectable absorption coefficient, was 4.7 x 10-9 W
      cm(-1).

PMID- 16807607
TI  - Control of giant pulse duration in neodymium minilasers with controllable cavity
      length and pulsed pumping.
AB  - In a solid-state laser incident on a LiNdP4O12 crystal, pumped by a short light
      pulse, giant pulse oscillation without the use of resonator Q switching is
      realized. Tuning of the oscillation pulse duration from 2 up to 20 ns is achieved
      by changing the cavity length from 24 to 3 mm, respectively. Our analysis of this
      mode of laser radiation is made on the basis of the rate equations. The factors
      influencing oscillation pulse duration are investigated. It is shown that in a
      limiting case the minimal value of the pulse duration is limited by only the rate
      of excitation transfer from the pumping band to the metastable level.

PMID- 16807608
TI  - Group-velocity-matched optical parametric oscillator in tilted quasi-phase
      matched gratings.
AB  - An achromatic phase-matching scheme is reported for an optical parametric
      oscillator in tilted quasi-phase-matched gratings. The spectral angular
      dispersion is introduced in interaction waves such that each wave component
      satisfies the two-dimensional (noncollinear) quasi-phase matching. This is
      equivalent to simultaneous quasi-phase matching and group-velocity matching for
      ultrashort pulses. The phase-matching bandwidth for 10 mm periodically poled KTP
      increases by a factor of 12 at lambdas = 1.7 microm compared with one-dimensional
      quasi-phase matching. The effective interaction length will increase as a result
      of the matching.

PMID- 16807609
TI  - Laser-induced fluorescence of ketones at elevated temperatures for pressures up
      to 20 bars by using a 248 nm excitation laser wavelength: experiments and model
      improvements.
AB  - Laser-induced fluorescence of acetone and 3-pentanone for a 248 nm excitation
      wavelength was investigated for conditions relevant for internal combustion
      engines regarding temperature, pressure, and gas composition. An optically
      accessible calibration chamber with continuous gas flow was operated by using CO2
      and air as a bath gas. According to the varying pressure and temperature
      conditions during the compression stroke of a spark ignition engine, fluorescence
      experiments were performed under isothermal pressure variations from 1 to 20 bars
      for different temperatures between 293 and 700 K. The ketone fluorescence
      behavior predictions, based on a model previously developed by Thurber et al.
      [Appl. Opt. 37, 4963 (1998)], were found to overestimate the pressure-related
      fluorescence increase for high temperature and small wavelength excitation at 248
      nm. The parameters influencing the model only in the large vibrational energy
      regime were newly adjusted, which resulted in an improved model with a better
      agreement with the experiment. The model's validity for excitation at larger
      wavelengths was not influenced. For the air bath gas an additional collision and
      vibrational energy sensitive quenching rate was implemented in the model for both
      tracers, acetone and 3-pentanone.

PMID- 16807610
TI  - Extension of geometrical-optics approximation to on-axis Gaussian beam
      scattering. I. By a spherical particle.
AB  - The geometrical-optics approximation of light scattering by a transparent or
      absorbing spherical particle is extended from plane wave to Gaussian beam
      incidence. The formulas for the calculation of the phase of each ray and the
      divergence factor are revised, and the interference of all the emerging rays is
      taken into account. The extended geometrical-optics approximation (EGOA) permits
      one to calculate the scattering diagram in all directions from 0 degrees to 180
      degrees. The intensities of the scattered field calculated by the EGOA are
      compared with those calculated by the generalized Lorenz-Mie theory, and good
      agreement is found. The surface wave effect in Gaussian beam scattering is also
      qualitatively analyzed by introducing a flux ratio factor. The approach proposed
      is particularly important to the further extension of the geometrical-optics
      approximation to the scattering of large spheroidal particles.

PMID- 16807611
TI  - Extension of geometrical-optics approximation to on-axis Gaussian beam
      scattering. II. By a spheroidal particle with end-on incidence.
AB  - On the basis of our previous work on the extension of the geometrical-optics
      approximation to Gaussian beam scattering by a spherical particle, we present a
      further extension of the method to the scattering of a transparent or absorbing
      spheroidal particle with the same symmetric axis as the incident beam. As was
      done for the spherical particle, the phase shifts of the emerging rays due to
      focal lines, optical path, and total reflection are carefully considered. The
      angular position of the geometric rainbow of primary order is theoretically
      predicted. Compared with our results, the Mobius prediction of the rainbow angle
      has a discrepancy of less than 0.5 degrees for a spheroidal droplet of aspect
      radio kappa within 0.95 and 1.05 and less than 2 degrees for kappa within 0.89
      and 1.11. The flux ratio index F, which qualitatively indicates the effect of a
      surface wave, is also studied and found to be dependent on the size, refractive
      index, and surface curvature of the particle.

PMID- 16807612
TI  - Quantitative flow visualization in supersonic jets through tomographic inversion
      of wavefronts estimated through shadow casting.
AB  - We present a simple method with which to reconstruct wavefronts that are
      transilluminating supersonic jets through measurement of their local slopes. The
      wavefront slopes are measured in two orthogonal directions by use of the average
      displacements suffered by a random-dot pattern in its shadow cast by the
      wavefront in front of it. A smooth wavefront is estimated from its measured
      slopes by a least-squares curve fitting technique. The calculated wavefront
      distortion is tomographically inverted to yield the density distributions of the
      object. The results are comparable to that obtained by use of a phase-retrieval
      algorithm from axial intensity transport measurements.

PMID- 16807613
TI  - Subnanosecond-resolution phase-resolved fluorescence imaging technique for
      biomedical applications.
AB  - Characterization of fluorescence emissions from cells often leads to conclusive
      results in the early detection of cellular abnormalities. Cellular abnormalities
      can be characterized by their difference in the fluorescence lifetime, which may
      be less than nanoseconds. A sensitive frequency domain technique, also called a
      phase-resolved fluorescence imaging technique, is proposed in which fluorescence
      emissions at the same wavelengths can more effectively be separated with
      subnanosecond resolution in their lifetime difference. The system configuration
      is optimized by incorporating even-step phase shifting in the homodyne-assisted
      signal-processing concept along with the phase-resolved fluorescence technique to
      eliminate the dc offsets of emission. Experiments are carried out with simulated
      samples composed of two fluorescence emissions of the same wavelength but with
      different lifetime values. Suppression of either of the fluorescence emissions by
      selective imaging of the other validates the superiority of the proposed
      technique. Hence, this technique can potentially be applied in the early
      detection of cellular abnormalities.

PMID- 16807614
TI  - Analytical solution for light propagation in a two-layer tissue structure with a
      tilted interface for breast imaging.
AB  - Reflectance measurement of breast tissue is influenced by the underlying chest
      wall, which is often tilted as seen by the detection probe. We develop an
      analytical solution of light propagation in a two-layer tissue structure with
      tilted interface and refractive index difference between the layers. We validate
      the analytical solution with Monte Carlo simulations and phantom experiments, and
      a good agreement is seen. The influence of varying the tilting angle of the
      interface on the reflectance is discussed for two types of layered structures.
      Further, we apply the developed analytical solution to obtain the optical
      properties of breast tissue and chest wall from clinical data. Inverse
      calculation using the developed solution applied to the data obtained from Monte
      Carlo simulations shows that the optical properties of both layers are obtained
      with higher accuracy as compared to using a simple two-layer model ignoring the
      interface tilt. This is expected to improve the accuracy in estimating the
      optical properties of breast tissue, thus enhancing the accuracy of optical
      tomography of breast tumors.

PMID- 16807615
TI  - High-resolution image reconstruction in fluorescence microscopy with patterned
      excitation.
AB  - We discuss data treatment strategies in structured illumination microscopy, using
      simulated and experimental data. In the setup, the illumination pattern is
      generated by projecting a movable pinhole mask into the sample, and a wide-field
      fluorescence microscope image is acquired for each pattern position. The
      structured illumination data obtained from a two-dimensional illumination pattern
      can be treated by projection strategies such as in video confocal microscopy
      (sum, maximum, maximum minus minimum, and superconfocal), by a scaled subtraction
      of the out-of-focus estimate, or by a modified version of the Fourier-space
      treatment, as is known for data from one-dimensional structured illumination. We
      investigate the influence of some data processing strategies on unwanted effects
      such as residual patterning and local deviations from linearity in the
      reconstructed intensity.

PMID- 16807616
TI  - New tools, old challenges: the emerging role of angiotensin receptor blockers in
      the treatment of the systolic hypertension epidemic.

PMID- 16807617
TI  - Eprosartan mesylate effectively reduces systolic and diastolic blood pressure in
      a Canadian primary care setting.
AB  - BACKGROUND: Evidence suggests that antihypertensive agents may have differential
      effects on systolic blood pressure (SBP) and that home BP monitoring (HBPM) may
      enhance the antihypertensive effects. OBJECTIVES: To evaluate the efficacy and
      safety of eprosartan mesylate in the treatment of hypertension, particularly on
      SBP in older subjects, and to assess the role of HBPM. METHODS: A randomized,
      open-label, 10-week study was conducted in 35 primary care centres across Canada.
      One hundred ninety-eight subjects (aged 60 to 84 years) with mild to moderate
      hypertension (SBP 140 mmHg to 179 mmHg, diastolic BP [DBP] 109 mmHg or less) were
      included in the analysis. All subjects received open-label eprosartan mesylate
      600 mg once daily, and were randomly assigned to eprosartan treatment alone or
      eprosartan plus HBPM. Hydrochlorothiazide 12.5 mg once daily could be added after
      week 4. The primary outcomes were the change in SBP at study end and the effect
      of HBPM on SBP. RESULTS: In the eprosartan and eprosartan plus HBPM groups, SBP
      was reduced by 17.6 mmHg and 19.9 mmHg, and DBP was reduced by 8.7 mmHg and 8.5
      mmHg, with a systolic pressure response of 58% and 65%, respectively. HBPM had no
      additional benefits. Eprosartan was well tolerated, with the majority of adverse
      events being mild to moderate. CONCLUSIONS: Eprosartan alone or in combination
      with hydrochlorothiazide was highly effective and safe in lowering blood
      pressure, notably SBP, in older subjects with mild to moderate hypertension.

PMID- 16807618
TI  - The angiotensin receptor blocker eprosartan mesylate reduces pulse pressure in
      isolated systolic hypertension.
AB  - BACKGROUND: Isolated systolic hypertension (ISH) is a common and particularly
      poorly controlled form of hypertension. OBJECTIVE: To assess the effect of
      eprosartan 600 mg tablet once daily on blood pressure (BP), pulse pressure, BP
      response, compliance and safety in subjects with ISH compared with subjects with
      combined systolic-diastolic hypertension (non-ISH). PATIENTS AND METHODS: The
      present study is a post hoc evaluation of a prospective, randomized, open-label,
      multicentre study. Subjects 60 to 84 years old with ISH (systolic BP 140 mmHg or
      greater with diastolic BP less than 90 mmHg) (n=97) or non-ISH (systolic BP 140
      mmHg or greater with diastolic BP 90 mmHg or greater) (n=98) received 10 weeks of
      treatment with either eprosartan alone or eprosartan plus home BP monitoring.
      RESULTS: Eprosartan significantly reduced systolic BP at the study end point from
      baseline in both the ISH group and the non-ISH group (-17.5+/-14.5 mmHg and 
      20.6+/-14.1 mmHg [mean +/- SD], respectively; P<0.0001). The reduction in
      diastolic BP was significantly greater in subjects with non-ISH than in those
      with ISH (-12.2+/-8.1 mmHg and -5.0+/-7.9 mmHg, respectively; P<0.0001). Mean
      pulse pressure was significantly reduced from baseline in both groups (P<0.0001),
      but was reduced to a significantly greater degree in the ISH group than in the
      non-ISH group (-12.5+/-12.3 mmHg and -8.4+/-11.1 mmHg, respectively; P<0.05). The
      most common adverse events were dizziness, headache and fatigue. CONCLUSIONS:
      Eprosartan effectively lowered BP and pulse pressure in all subjects. The
      magnitude of pulse pressure reduction was significantly greater in the ISH group,
      and the diastolic BP reduction was greater in the non-ISH group, suggesting that
      eprosartan may be especially suitable in the treatment of subjects with ISH.

PMID- 16807619
TI  - The effect of treatment with eprosartan on pulse pressure: factors predicting
      response.
AB  - BACKGROUND: Pulse pressure is an important cardiovascular risk factor,
      particularly in the elderly and in patients with isolated systolic hypertension.
      The differential impact of antihypertensive agents on pulse pressure is not
      known. OBJECTIVE: To assess the antihypertensive effect of treatment with the
      angiotensin II receptor blocker eprosartan on pulse pressure, and the factors
      influencing this effect. METHODS: The present study was an observational study of
      4067 patients (55% women, mean age 67 years) with essential hypertension, newly
      diagnosed or unresponsive to current treatment, in which 3133 patients received
      12 weeks of treatment with eprosartan 600 mg/day (87% monotherapy) in primary
      care centres. Blood pressure was measured using a validated oscillometric device
      (Omron 705CP, Omron Healthcare Inc, USA). RESULTS: Eprosartan significantly
      reduced pulse pressure at 12 weeks (13.5 mmHg, P<0.001). The reductions in
      systolic, diastolic and mean blood pressures were also statistically significant
      (26.0 mmHg, 12.6 mmHg and 17.1 mmHg, respectively). After correcting the pulse
      pressure for hypertension severity (pulse pressure/mean blood pressure ratio),
      this index was reduced from 62% to 58% with eprosartan, suggesting a 4% reduction
      in the pulsatile component. This reduction was more pronounced in patients over
      60 years of age, those with a higher index at baseline and those with
      hypertensive cardiovascular complications. Adverse drug reactions occurred in
      1.5% of patients. CONCLUSION: Eprosartan is an effective, well tolerated
      antihypertensive drug that reduces pulse pressure. This reduction is partially
      independent of the severity of high blood pressure, which may be important for
      both safety and target organ protection.

PMID- 16807620
TI  - Liver transplantation. Introduction.

PMID- 16807621
TI  - Steroid avoidance in liver transplantation.
AB  - Corticosteroids have always played a valuable role in transplantation.
      Unfortunately, they are subject to a wide range of side effects, such as
      hyperlipidemia, hypertension, diabetes mellitus, osteoporosis, growth retardation
      and Cushingoid appearance. Steroids may also exacerbate problems that existed
      before surgery, including malignancy, hepatitis B and hepatitis C. New, powerful
      immunosuppressants have allowed steroid use to be reduced or avoided altogether,
      but use of these regimens is not simple and may be associated with late acute
      rejection and recurrence of autoimmune disease. The present review examines the
      rationale for steroid avoidance in liver transplantation and assesses the new
      regimens that are currently being developed.

PMID- 16807622
TI  - Practical considerations of right lobe living donor liver transplantation in
      adults.
AB  - The practice of living donor liver transplantation in adults has developed
      rapidly over the past five years and brings with it a set of unique technical and
      ethical challenges. The evaluation of potential donors focuses on their health
      and motives, and the results of noninvasive imaging, with the objective of
      ensuring the best outcomes for both donors and recipients. Graft volume is
      critical to success, and venous outflow reconstruction is paramount, although
      there is no consensus on the preferred method. Biliary tract complications occur
      in 30% of recipients. Complications that may interfere with recovery or delay the
      return to well-being occur in one of every four or five donors. The precise risk
      of donor death cannot be stated with certainty because comprehensive data on all
      cases are not available. It is clear, however, that donation of the right lobe of
      the liver carries with it a much greater risk of mortality than kidney donation.
      The paucity of details reported on donors who have died make it impossible to
      determine to what extent the deaths were preventable. The option of living
      donation is an invitation to expand the criteria for recipient selection to
      include, for example, patients with tumours that exceed traditional transplant
      guidelines. The risk-benefit ratios for donors become especially problematic when
      post-transplant recipient survival is below current standards.

PMID- 16807623
TI  - The challenge of recurrent hepatitis C virus in liver transplant recipients.
AB  - Hepatitis C virus (HCV) has become the leading indication for liver
      transplantation (LT) worldwide. Short-term graft and patient survival after LT in
      these individuals is comparable with other indications for LT. There is, however,
      a disturbing trend for decreased survival over the longer term. The natural
      history of HCV infection after LT is evolving. Its early recurrence and the wide
      spectrum of recurrent disease is recognized, from minimal histological and
      clinical disease to very aggressive forms of hepatic damage such as fibrosing
      cholestatic hepatitis. There is growing concern that recurrent HCV is becoming
      more aggressive. Although many factors have been implicated, the causes have not
      been fully elucidated. Interferon-based antiviral therapy is challenging to use
      in this patient population because of significant toxicity. Nevertheless, these
      agents have some efficacy, and pegylated interferons, which are now being used
      more frequently, achieve superior response rates. The role of liver
      retransplantation in this patient population is controversial, because of both a
      reduced survival rate and an overall shortage of organ donors. The present review
      discusses the challenges that occur in LT recipients with HCV.

PMID- 16807625
TI  - The South African Hypertension Guideline 2006: a major step forward for improved
      management of hypertension.

PMID- 16807624
TI  - Renal dysfunction in liver transplantation: the problem and preventive
      strategies.
AB  - Ongoing improvements in survival following liver transplantation have
      necessitated a re-evaluation of immunosuppression protocols. Corticosteroids and
      calcineurin inhibitors (CNIs) are the most frequently used immunosuppressive
      drugs for liver transplantation but are associated with a wide range of adverse
      effects, such as hypertension, hyperlipidemia and nephrotoxicity. The need for
      hemodialysis after liver transplantation is associated with poor outcomes. Renal
      dysfunction in this setting may be caused by pre-existing renal disease,
      hepatorenal syndrome and/or post-transplant factors, including the use of
      nephrotoxic drugs, most notably CNIs such as cyclosporine and tacrolimus. The
      methods that address this problem include the diligent control of metabolic
      factors (eg, hypertension and hyperlipidemia), therapeutic monitoring of CNIs and
      withdrawal or reduction of the dosage of CNIs, combined with the use of newer non
      nephrotoxic agents. Although there is no clear consensus about the most effective
      strategy, the optimal long-term immunosuppressive regimen would prevent rejection
      without causing nephrotoxicity or other significant adverse effects. Recent
      evidence suggests that the liver is a tolerogenic organ and that some patients
      may need little, if any, long-term immunosuppression.

PMID- 16807626
TI  - Consequence of resistance training on body composition and coronary artery
      disease risk.
AB  - Coronary artery disease (CAD) is a substantial cause of death and disability in
      South Africa and Western society, with research showing obesity to be one of the
      most common CAD risk factors. Furthermore, obesity is speculated to be the
      fastest-growing CAD risk factor and to become the most prevalent CAD risk factor.
      Research on obesity is therefore essential, and we propose some preventative
      measures that will hopefully limit the expansion of this risk factor for CAD.
      Most of the literature has focused primarily on aerobic modes of exercise. The
      aim of this study, therefore, was to investigate whether resistance training
      would improve body composition. Twenty-eight males were matched by age,
      percentage of body fat and waist-to-hip ratio and randomly assigned either to a
      resistance-training group (n = 13) or a control group (n = 15). Each subject's
      body mass, percentage body fat, lean mass, fat mass, waist-to-hip ratio and body
      mass index were assessed both pre- and post-experimentally following the eight
      week experimental period. The resistance-training group trained three times
      weekly at 60% of their one-repetition maximum using nine resistance exercises.
      Each exercise was performed for three sets of 15 repetitions each, whereas the
      control group did not exercise over this period. The dependent t-test indicated
      that resistance training significantly changed body mass, percentage of body fat,
      lean mass and fat mass (all had a p-value of 0.00; p <or= 0.01). Furthermore, the
      independent t-test demonstrated that lean mass, fat mass and percentage of body
      fat were statistically significantly different between the control and resistance
      training groups. In conclusion, resistance training improved four of the six
      measured body composition variables, therefore implying that resistance training
      does in fact improve the majority of body composition variables and therefore CAD
      risk.

PMID- 16807627
TI  - Vasorelaxant and hypotensive effects of Sclerocarya birrea (A Rich) Hochst
      (Anacardiaceae) stem bark aqueous extract in rats.
AB  - The vasorelaxant and hypotensive effects of Sclerocarya birrea stem bark aqueous
      extract have been examined in rat experimental paradigms. Cumulative additions of
      S birrea stem bark aqueous extract (SBE 12.5-200 mg/ml) to the bath fluid induced
      concentration-dependent relaxations of endothelium- containing normotensive
      Wistar rat isolated aortic rings pre-contracted with noradrenaline (NA). The
      vasorelaxant effect of SBE on endothelium-containing isolated aortic rings was
      annulled by removal of the functional endothelium (in endothelium-denuded
      normotensive Wistar rat isolated aortic rings), or by pretreatment of the
      endothelium-containing isolated aortic rings with NG-nitro-L-arginine methyl
      ester (L-NAME), an inhibitor of nitric oxide synthase (NOS). Bolus intravenous
      administrations of the plant extract (SBE 25-400 mg/kg iv) caused transient, dose
      dependent and significant (p < 0.05-0.001) reductions in systemic arterial blood
      pressure and heart rates of anaesthetised normotensive and hypertensive Dahl salt
      sensitive rats. The findings of this experimental animal study suggest that S
      birrea stem bark aqueous extract relaxes normotensive Wistar rat aortic vascular
      smooth muscle via endothelium-dependent nitric oxide (NO); and that the
      hypotensive effect of the plant extract is likely to be mediated, at least in
      part, through nitric oxide synthase activation and subsequent nitric oxide
      release.

PMID- 16807628
TI  - Cardiovascular disease and hormone replacement therapy in post-menopausal women.

PMID- 16807629
TI  - Cryopreservation of platelets at the end of their conventional shelf life leads
      to severely impaired in vitro function.
AB  - Storage time for platelet concentrates (PCs) is limited to five days due to
      'aging' of the platelets and an increasing risk of bacterial proliferation.
      Storage time can be prolonged by cryopreservation. We investigated in vitro
      function of six consecutive PCs at the end of their conventional shelf life
      followed by cryopreservation for 24 hours. Spontaneous, adenosine diphosphate
      (ADP)-induced and collagen-induced activation before and after cryopreservation
      were determined by flow cytometry. Additionally, ADP- and collagen-induced
      aggregation was measured. After cryopreservation two-thirds of the platelets were
      spontaneously activated, twice as many as before the procedure (p < 0.001). ADP
      induced activation was significantly reduced (p = 0.014). Collagen-induced
      activation was unchanged. Aggregation stimulated by ADP and collagen was
      significantly reduced (p = 0.005 and p = 0.009, respectively). Our results show
      severely impaired in vitro function of platelets after storage at 22 degrees C
      for five days followed by cryopreservation. Cryopreservation of PCs after a
      storage time of five days cannot be recommended.

PMID- 16807630
TI  - Comprehensive assessment of left ventricular pseudo-aneurysms with magnetic
      resonance imaging.
AB  - In a small number of patients, myocardial infarction, trauma, infection or
      cardiac surgery are complicated by incomplete wall rupture and pseudo-aneurysm
      formation. We describe the advances made in the non-invasive assessment of this
      condition with the introduction of magnetic resonance imaging (MRI) and discuss
      the value of specific MRI techniques for comprehensive structural and functional
      cardiac assessment.

PMID- 16807631
TI  - Homocysteine in vascular disease: an emerging clinical perspective.
AB  - Traditionally, arterial and venous thrombo-embolism has been attributed to
      pathophysiological lesions in the vessel wall, or altered blood contents or flow
      through the lumen. Logically these fall into the category of a high-shear system,
      as opposed to the rather different circumstances in slowly moving columns of
      blood. The re-evaluation of this belief has been prompted by acknowledgement that
      there is currently a shift in emphasis. Recently we have recognised a common
      central factor in the internal dysfunction of the vessel that precedes and so
      initiates thrombocyte adhesion.

PMID- 16807632
TI  - Analysis of a medical aid administrator database for costs and utilisation of
      benefits by patients claiming for lipid-lowering agents.
AB  - OBJECTIVE: This is a descriptive study to analyse overall costs of medical scheme
      beneficiaries using lipid-lowering agents. The purpose of the analysis was to
      relate claims for lipid-lowering agents to utilisation and costs of drugs and
      services. METHODS: An analysis was undertaken of physician visits, cardiac
      related disease co-morbidities and hospitalisation. Any medication or dose
      changes were also analysed, including those after hospitalisation. RESULTS: A
      total of 100 691 patients were identified, clustered around the age groups of 40
      to 70 years, of whom 60% were males. The cohort consisted ethnically mainly of
      whites (68%), with an even distribution (6-9%) of Asian, black and Coloured
      subjects. Of these patients, approximately a third had recorded co-morbidities,
      mainly hypertension (58.6%) and the more prevalent cardiovascular (ischaemic
      heart disease, coronary artery disease) and metabolic disorders. While drug costs
      accounted for approximately 28% of total costs, hospitalisation cost (66%) was by
      far the greatest cost driver. Whereas drug costs appeared to have decreased over
      the period of analysis, hospitalisation costs had increased dramatically.
      Patients appeared to be stable on initial prescribed drug therapy with a
      relatively low incidence of switching (< 25%), mainly to the generic,
      simvastatin. Adherence to statin therapy was remarkably high at 85%. CONCLUSIONS:
      Despite the manifold shortcomings, mainly due to the lack of ICD10 coding and
      information on critical clinical parameters, the study gives some brief insights
      into the burden of managing patients with cardiovascular diseases and provides a
      basis for improving future studies.

PMID- 16807633
TI  - Isolated left ventricular non-compaction as a cause of thrombo-embolic stroke: a
      case report and review.
AB  - Isolated left ventricular non-compaction is the result of incomplete myocardial
      morphogenesis, leading to persistence of the embryonic myocardium. The condition
      is recognised by an excessively prominent trabecular meshwork and deep
      intertrabecular recesses of the left ventricle. These intertrabecular recesses
      are prone to thrombus formation, with resultant embolic sequelae. We describe a
      case of cerebral thrombo-embolism in a young woman due to isolated left
      ventricular non-compaction.

PMID- 16807634
TI  - Images in cardiology. Thoracic pain and T-wave inversion.

PMID- 16807642
TI  - Immunomagnetic isolation and FACS--competing techniques for the enumeration of
      circulating endothelial cells.

PMID- 16807643
TI  - A common origin of the 4143insA ADAMTS13 mutation.
AB  - Severely deficient activity of the von Willebrand Factor (VWF) cleaving
      metalloprotease, ADAMTS13, is associated with thrombotic thrombocytopenic purpura
      (TTP). The mutation spectrum ofADAMTS13 is rather heterogeneous, and numerous
      mutations spread across the gene have been described in association with
      congenital TTP. The 4143insA mutation is unusual with respect to its geographic
      concentration. Following the initial report from Germany in which the 4143insA
      mutation was detected in four apparently unrelated families, we have now
      identified this mutation in a further eleven patients from Norway, Sweden,
      Poland, Germany, the Czech Republic and Australia. Confirmation that the
      Australian patient is of German ancestry, together with the Northern and Central
      European origin of most of the other patients, suggests that the 4143insA
      mutation has a common genetic background. We established ADAMTS13 haplotypes by
      analyzing 17 polymorphic intragenic markers. The haplotypes linked to 4143insA
      were identical in all informative families. Three novel candidate mutations,
      C347S, P671L and R1060W, as well as the known mutation R507Q, were also
      identified during the course of the study. We conclude that 4143insA has a common
      genetic background and is frequent among patients with hereditary ADAMTS13
      deficiency in Northern and Central European countries.

PMID- 16807645
TI  - Factor V Leiden mutation and pregnancy-related venous thromboembolism: what is
      the exact risk? Results from a meta-analysis.
AB  - The magnitude of the association of factor V Leiden mutation with pregnancy
      related venous thrombosis remains unclear. Our objective was to undertake a
      systematic review and a metaanalysis of the literature to estimate precisely the
      association of factorV Leiden mutation with the risk of first, or recurrent,
      pregnancy-related venous thromboembolism. Studies published before October 2005
      were identified by Medline((R)). Using both fixed and random effect models, odds
      ratios (OR) with accompanying 95% confidential intervals (CI) were calculated for
      the factor V Leiden mutation and the clinical end-point (Yusuf-Peto adaptation of
      the Mantel-Haenszel, DerSimonian and Laird method). We identified 13 studies
      including 7 cohorts and 6 casecontrol studies relating to factor V Leiden and
      pregnancy-related venous thrombosis. The results from the cohorts showed a pooled
      OR of 4.46 (95% CI, 1.82-10.94; 7,879 pooled women), with no evidence of
      statistical heterogeneity (p = 0.36), for the risk of a first venous
      thromboembolism during pregnancy or the postpartum period associated with the
      factor V Leiden mutation. Case-control studies revealed a higher risk (OR 8.6,
      95% CI, 5.85-12.63; 1,433 [corrected] pooled women) with significant
      heterogeneity (p < 0.005). Because of insufficient data, an analysis for the risk
      of recurrence could not be performed. Our findings emphasize the fact that
      limited data are available on this topic. This meta-analysis provides clinicians
      with an estimate of the average risk of a first thrombosis occurring during
      pregnancy in women carrying the factor V Leiden to assist the management of such
      women.

PMID- 16807644
TI  - Antithrombotic properties of Ixolaris, a potent inhibitor of the extrinsic
      pathway of the coagulation cascade.
AB  - Ixolaris is a two-Kunitz tick salivary gland protein identified in Ixodes
      scapularis that presents extensive sequence homology to TFPI. It binds to FXa or
      FX as scaffolds and inhibits tissue factor/FVIIa complex (extrinsic Xnase).
      Differently from TFPI, ixolaris does not bind to the active site cleft of FXa.
      Instead, complex formation is mediated by the FXa heparin-binding exosite, which
      may also results in decreased FXa activity into the prothrombinase complex. In
      this report, we show that recombinant (125)I-ixolaris interacts with rat and
      human FX in plasma and prolongs the prothrombin time (PT) and activated partial
      thromboplastin time (aPTT) in vitro. We have also investigated the effects of
      ixolaris in vivo, using a venous thrombosis model. Subcutaneous (s.c.) or
      intravenous (i.v.) administration of ixolaris in rats caused a dose-dependent
      reduction in thrombus formation, with complete inhibition attained at 20
      microg/kg and 10 microg/kg, respectively. Antithrombotic effects were observed 3
      h after s.c. administration of ixolaris and lasted for 24 h thereafter. Ex vivo
      experiments showed that ixolaris (up to 100 microg/kg) did not affect the aPTT,
      while the PT was increased by approximately 0.4-fold at the highest ixolaris
      concentration. Remarkably, effective antithrombotic doses of ixolaris (20
      microg/kg) was not associated with bleeding which was significant only at higher
      doses of the anticoagulant (40 microg/kg). Our experiments demonstrate that
      ixolaris is an effective and possibly safe antithrombotic agent in vivo.

PMID- 16807646
TI  - Antiphospholipid antibodies and hyperhomocysteinaemia in patients with vascular
      occlusive disease.
AB  - Hyperhomocysteinemia (HHcy), lupus anticoagulant (LA) and anticardiolipin
      antibodies (ACA) are independent risk factors for thrombosis. Even though risks
      are cumulative, the clinical impact of the association is unknown. Preliminary
      data suggested that HHcy might be associated with transient LA and ACA,
      disappearing after lowering HHcy. We prospectively evaluated the association of
      HHcy and LA/ACA, the effect of lowering HHcy with folic acid in LA behavior, and
      the correlation of the initial dRVVT with LA behavior after folic acid in 210
      patients with thrombosis and adverse pregnancy outcomes. Prevalence of HHcy among
      patients with LA/ACA was 40%. Thirty-one patients exhibited only HHcy (15%; Group
      1), 106 (50%; Group 2) had only LA/ACA, while 73 (35%; Group 3) had both. After
      therapy, 63% and 64% of LA/ACA remained positive in Group 3 and 2, respectively.
      We observed a trend towards a more positive dRVVT in persistent LA after lowering
      HHcy. No differences in clinical presentation or in outcomes after two years of
      followup were observed among the groups. Even though the association of HHcy and
      LA/ACA is common in patients with thrombosis, it might have no prognostic
      implications if Hcy levels are lowered. Currently, no laboratory findings
      correlate with LA behavior, which is independent of homocysteine levels and
      vitamin treatment.

PMID- 16807647
TI  - Interleukin-10 promoter polymorphism and venous thrombosis: a case-control study.
AB  - The human interleukin-10 promoter gene is highly polymorphic. IL-10 polymorphisms
      have been associated with various autoimmune and lymphoproliferative disorders.
      Although IL-10 has been shown to modulate thrombin generation in several
      experimental models, it is not known whether IL-10 polymorphisms could be a risk
      factor for venous thrombosis. We therefore conducted a case-control study
      comparing 74 consecutive patients who experienced at least one episode of
      documented venous thromboembolic event and 100 healthy controls. All subjects
      were Caucasians. Five polymorphisms of the IL-10 promoter gene were studied: two
      highly polymorphic dinucleotide repeats, IL-10 R and IL-10G, and three single
      nucleotide polymorphisms at position -1082, -819 and -592. Factor VG1691C Leiden
      mutation was systematically determined. Multivariate logistic regression analysis
      showed that IL-10 G13 and G10 alleles are independent risk factors for venous
      thrombosis (Odds ratio:OR = 3.33, p = 0.003 and OR = 2.83, p = 0.03,
      respectively). Furthermore, IL-10 G10 allele is more frequent in recurrent
      disease.

PMID- 16807648
TI  - Flow cytometry-sorted non-viable endotoxin-treated human monocytes are strongly
      procoagulant.
AB  - Monocytes/macrophages are important in disease states such as gram-negative
      sepsis and coronary artery disease. Following exposure to lipopolysaccharide
      (LPS), monocytes express tissue factor (TF), the main initiator of blood
      coagulation. We previously demonstrated that human monocytes treated with high
      concentrations of LPS, or with LPS and calcium ionophore, displayed higher TF
      activity than monocytes treated with only low concentrations of LPS, even though
      the monocytes under all conditions expressed similar amounts of cell surface TF
      antigen. Such restrainedTF activity is often referred to as encryption and its
      release as de-encryption. We also observed that the increase in TF activity, de
      encryption, coincided with an increase in cell surface phosphatidylserine (PS)
      representing apoptosis and necrosis. In the present work, we separated LPS and
      LPS and calcium ionophore-treated human monocytes into two populations, one of
      mainly viable, PS negative cells, and one of mainly non-viable, PS positive
      cells, by sorting flow-cytometry. We observed that non-viable cells expressed
      considerably less TF antigen than viable cells. Despite this, non-viable cells
      were clearly more procoagulant than viable cells in two different coagulation
      assays. Procoagulant activity was dependent on both TF and PS. We consider the
      higher content of externalized PS in non-viable monocytes as the major reason for
      the stronger procoagulant activity of these cells. Thus, TF de-encryption appears
      largely to occur on PS positive, non-viable cells under these conditions. This
      supports the important role of PS in coagulation, and it suggests that PS
      expression signifying cell death, may be clinically relevant.

PMID- 16807649
TI  - Enhanced platelet activation by prolactin in patients with ischemic stroke.
AB  - Prolactin and leptin are newly recognised platelet co-stimulators due to
      potentiation of ADP-induced platelet aggregation. Elevated leptin levels have
      recently been found to be a risk factor for ischemic stroke in both men and
      women, and especially in combination with increased blood pressure for
      hemorrhagic stroke in men. Until now an association between hyperprolactinemia
      and ischemic stroke has not been investigated systematically. We determined
      plasma prolactin and leptin levels as well as platelet P-selectin expression in
      36 patients with ischemic stroke or transient ischemic attack and detected a
      significant correlation between increased prolactin values and enhanced ADP
      stimulated P-selectin expression on platelets. In contrast, no correlation of
      leptin values with platelet P-selectin expression was found. Next we determined
      plasma prolactin and leptin as well as acquired and congenital risk factors of
      thrombophilia in patients with first-ever non-hemorrhagic stroke with or without
      atrial fibrillation. Excluding patients with such preexisting risk factors, 21
      patients with and 59 patients without atrial fibrillation were identified.
      Patients without atrial fibrillation revealed significantly higher plasma
      prolactin levels than patients with atrial fibrillation. Furthermore, the
      influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression
      in vitro was tested, showing that aspirin was without effect, whereas clopidogrel
      significantly inhibited platelet P-selectin expression. In conclusion,
      hyperprolactinemia might be a novel risk factor for stroke mediating its
      thrombogenic effect through enhanced platelet reactivity, and this might
      correspond to a higher efficacy of antiplatelet combination therapy with
      clopidogrel compared to aspirin therapy alone.

PMID- 16807650
TI  - Detection and quantification of mature circulating endothelial cells using flow
      cytometry and immunomagnetic beads: a methodological comparison.
AB  - Mature circulating endothelial cells (CECs) are novel cellular markers of
      endothelial damage/dysfunction. The two main techniques of CEC enumeration are
      flow cytometry (FC) and immunomagnetic bead (IB) isolation. Both quantify CECs
      accurately, but a direct comparison of both methods has not been reported. We
      sought to assess the agreement between the two methods in two patient
      populations, and a group of healthy subjects, with emphasis given to
      methodological issues. We included 34 patients with acute coronary syndrome
      (ACS), 60 patients with primary breast cancer (PBC) and 30 healthy controls (HC).
      We quantified CECs using the IB method [CD146 and FITCUlex europaeus lectin-1]
      and FC [CD45, CD34 and CD146]. Bland-Altman plots suggested reasonable agreement
      (<5% of events >2 standard deviations from the mean) between FC and the IB
      methods for CEC quantification in whole blood in the two disease groups (ACS and
      PBC), but not among the HCs. There were no statistically significant differences
      in CEC levels by the two methods amongst all three patient groups. There is
      reasonable agreement between the FC and the IB methods for mature CEC
      quantification in whole blood, especially amongst disease groups. The agreement
      between the two methods appears to weaken in healthy controls, and at lower and
      higher absolute CEC counts.

PMID- 16807651
TI  - Endothelial dysfunction and systemic inflammation in persons with echolucent
      carotid plaques.
AB  - Echolucent carotid plaques are associated with high risk for future ischemic
      cerebrovascular events independent of the degree of stenosis. Elevated levels of
      markers of systemic inflammation and endothelial dysfunction are predictors for
      future myocardial infarction and stroke. The present study was undertaken to
      investigate the relations between plaque morphology, endothelial dysfunction
      assessed by tissue-plasminogen activator antigen (t-PA ag) and vonWillebrand
      factor (vWF), and systemic inflammation in persons with carotid stenosis. We
      conducted a crosssectional study including 133 persons with carotid stenosis and
      138 controls without stenosis recruited from the populationbased Tromso Study.
      High-resolution B-mode and colour Doppler/pulsed-wave Doppler ultrasonography of
      both carotid arteries was performed, and plaque morphology in terms of
      echogenicity was assessed. Persons with carotid stenosis had significantly higher
      plasma t-PA and vWF concentrations than controls. There was a significant inverse
      relationship between t-PA ag and plaque echogenicity (p = 0.034). The increased
      plasma t-PA ag in persons with carotid stenosis was not associated with increased
      plasminogen activator inhibitor-I (PAI-1). Persons with echolucent carotid
      plaques had higher degree of systemic inflammation, and plasma t-PA and vWF
      concentration increased significantly across quartiles of WBC, fibrinogen, and hs
      CRP. Our findings may suggest that plasma t-PA may be superior to vWF as a marker
      for endothelial dysfunction due to its ability to discriminate between various
      plaque echogenicity, and that the predictive role of t-PA ag in cardiovascular
      disease is independent of inhibited fibrinolysis.

PMID- 16807652
TI  - Turnover and fate of fibrinogen and platelets at the rabbit aorta wall
      immediately after a balloon de-endothelializing injury in vivo.
AB  - A de-endothelializing injury to the artery wall in vivo results in a rapid
      procoagulant response at the surface of the exposed subendothelium. Activated
      tissue factor (TF)-bearing cells and hemostasis factors located at the site of
      injury respond by producing thrombin, and within minutes the principal thrombus
      forming, blood-borne components (platelets, fibrinogen) accumulate at the site.
      To compare their behaviors, the rates of uptake and turnover of rabbit (51)Cr
      platelets and rabbit (125)I-fibrinogen were quantified simultaneously during the
      initial 100-min interval after a balloon catheter injury to the rabbit aorta in
      vivo. Platelets ( approximately 70,000/mm(2)) and fibrin(ogen) ( approximately
      2.8 pmol/cm(2)) saturated the ballooned aorta surface within five minutes after
      injury. Whereas the adherent platelet and fibrinogen concentrations remained
      steady at the aorta surface, fibrin(ogen)-related products continued to
      accumulate slowly in the tunica media (TM) for at least 100 minutes. A relatively
      small proportion (3.7%/min) of adhered platelets turned over at the ballooned
      aorta surface at 10 minutes, decreasing to 1.2%/min at 100 minutes. By contrast,
      a larger proportion of fibrin(ogen) ( approximately 20%/min) was turned over
      within the platelet layer at 10 minutes, decreasing to 6%/min at 100 minutes. As
      verified by immunostaining aorta sections and by protein analysis of TM extracts,
      the uptakes of platelets and fibrinogen at the site of injury contributed to an
      accumulation of products of platelet releasate and fibrin(ogen) degradation
      (FDPs) within the TM. These observations improve our understanding of the
      hemostatic processes and subsequent events that occur after an arterial injury in
      vivo.

PMID- 16807653
TI  - Early in vivo anticoagulation inhibits the angiogenic response following hindlimb
      ischemia in a rodent model.
AB  - Emerging findings have demonstrated the critical role of blood clotting factors
      in the formation and stabilization of embryonic blood vessels. Whether a similar
      role is true during post-natal angiogenesis remains to be determined. Here we
      sought to determine whether the suppression of thrombin generation with
      anticoagulant drugs at doses routinely used for therapeutic purposes would affect
      the angiogenesis pattern following hindlimb ischemia in rats. Animals were
      treated with r-hirudin or enoxaparin within six hours post induction of hindlimb
      ischemia, whereas two other groups received oral anticoagulation warfarin
      beginning at day 3 post-ischemia or saline (as control). The revascularization
      anatomical and functional responses were evaluated 30 days following tissue
      ischemia. Chronic administration of the drugs resulted in stable anticoagulation
      in all animals throughout the experiment. Animals that received drugs with fast
      anticoagulation effects (i.e. r-hirudin and enoxaparin) presented a significant
      decrease in capillary density and capillary-to-myocyte ratio compared to control
      animals. These effects were not associated with changes in relative perfusion of
      the hindlimb at steady state. These anti-angiogenic effects occur in a time
      dependent manner, since delayed inhibition of coagulation (>72 hours) presents no
      adverse effect on the angiogenic response. We conclude that the use of
      anticoagulant drugs immediately after tissue ischemia induction hampers in vivo
      angiogenic response in a rodent hindlimb ischemia model.

PMID- 16807654
TI  - Identification of factor inhibitors by diagnostic haemostasis laboratories: a
      large multi-centre evaluation.
AB  - We have assessed the proficiency of diagnostic haemostasis facilities to
      correctly identify coagulation factor abnormalities and inhibitors. Forty-two
      laboratories participating in the external Quality Assurance Program (QAP)
      conducted by the RCPA agreed to participate and were each sent a set of eight
      samples (each 3 x 1 ml) for evaluation. They were asked to blind test these
      samples for the presence or absence of inhibitors, and where identified, to
      perform further analysis (including specific inhibitor analysis). In order to
      make the exercise more challenging, in addition to true factor inhibitors,
      samples were provided that reflected potential pre-analytical variables that
      might arise and complicate inhibitor detection or lead to false inhibitor
      identification. In brief, the sample set comprised a true high level factor (F) V
      inhibitor, a true moderate level FVIII inhibitor (but sample was
      defibrinogenated), a true lupus anticoagulant (LA), a normal (but slightly aged)
      plasma sample, a normal serum sample, a normal EDTA sample, an oral
      anticoagulant/vitamin K deficiency sample, and a gross heparin ( approximately 10
      U/ml) contaminated sample. Sixty-three percent of participants correctly
      identified the true FV inhibitor as such, although the reported range varied
      greatly [10 to >250 Bethesda units (BU/ml)] and 46% correctly identified the true
      FVIII inhibitor, despite the complication of the sample presentation, although
      the reported range also varied (7 to 64 BU/ml). Some laboratories either failed
      to identify the inhibitor present, or misidentified the inhibitor type. The LA,
      the oral anticoagulant/vitamin K deficiency, the normal serum sample, and the
      normal (aged) sample were also correctly identified by most laboratories, as was
      the absence of specific factor inhibitors in these samples. However, a small
      subset of laboratories incorrectly identified the presence of specific factor
      inhibitors in some of these samples. The heparin sample was also correctly
      identified by most (68%) laboratories. In contrast, the normal EDTA sample was
      misidentified as a FV and/or FVIII inhibitor by most (68%) laboratories, and only
      one laboratory correctly identified this as an EDTA sample. Thus, we conclude
      that although laboratories are able, in most cases, to identify the presence of
      true factor inhibitors, there is a large variation in identified inhibitor levels
      and there are also some significant errors in identification (i.e. false
      negatives and misidentifications). In addition, there is a significant false
      positive error rate where some laboratories will identify the presence of
      specific factor inhibitors where no such inhibitor exists (i.e. false positives).

PMID- 16807655
TI  - Sensitivity and specificity of a quantitative point of care D-dimer assay using
      heparinized whole blood, in patients with clinically suspected deep vein
      thrombosis.
AB  - D-dimer assays are efficient in the exclusion diagnostics of deep vein thrombosis
      (DVT) in patients without severe concomitant diseases. We have determined
      diagnostic sensitivity and specificity of a new point-of-care rapid assay for
      quantitative determination of D-dimer in heparinized whole blood in outpatients
      with suspected DVT. In 19 participating centers, 637 patients were included in
      the study, of which 77 were excluded, the majority because of inadequate
      documentation of analytical quality control measures. DVT was diagnosed in 223 of
      the remaining 560 patients by duplex ultrasound examination. The POC D-dimer
      assay showed a high sensitivity of 96.9% for the diagnosis of DVT and a high
      specificity of 60.8% at a pre-specified cutoff of 0.5 microg/ml. For Tina-quant D
      dimer, sensitivity was slightly lower at 94.9%, with a specificity of 64.8%. The
      VIDAS D-dimer assay showed a sensitivity of 98.2%, but specificity was 40.7%. The
      area under the curve (AUC +/- standard error, 95% confidence interval) was 0.879
      +/- 0.019 (0.845-0.909) for POC D-dimer, 0.908 +/- 0.016 (0.877-0.934) for Tina
      quant D-dimer, and 0.895 +/- 0.018 (0.862-0.922) forVIDAS D-dimer. Differences
      were not statistically significant. The new whole blood POC D-dimer assay is a
      reliable tool for exclusion of DVT in symptomatic outpatients, displaying a
      comparable diagnostic performance as VIDAS D-dimer and Tina-quant D-dimer assays.

PMID- 16807656
TI  - Rituximab in the treatment of acquired factor VIII inhibitors.

PMID- 16807657
TI  - Dysfibrinogenemia (fibrinogen Wilmington) due to a novel Aalpha chain truncation
      causing decreased plasma expression and impaired fibrin polymerisation.

PMID- 16807658
TI  - Cerebral venous thrombosis as a rare onset of Churg-Strauss syndrome.

PMID- 16807659
TI  - Extensive thromboembolic event as initial presentation of monoclonal gammopathy
      of undetermined significance.

PMID- 16807660
TI  - Accurate characterization of the IVS7 repeat polymorphism of FVII gene and
      identification of three novel allelic forms.

PMID- 16807661
TI  - Protein Z gene polymorphisms (intron F 79 G>A; -13 A>G) are not associated with
      acute coronary syndromes.

PMID- 16807662
TI  - Analysis of thrombotic factors in severe acute respiratory syndrome (SARS)
      patients.

PMID- 16807663
TI  - Decreased brain-derived neurotrophic factor (BDNF)- and beta-thromboglobulin
      (beta-TG)- blood levels in Alzheimer's disease.

PMID- 16807664
TI  - Arsenic carcinogenesis in the skin.
AB  - Chronic arsenic poisoning is a world public health issue. Long-term exposure to
      inorganic arsenic (As) from drinking water has been documented to induce cancers
      in lung, urinary bladder, kidney, liver and skin in a dose-response relationship.
      Oxidative stress, chromosomal abnormality and altered growth factors are possible
      modes of action in arsenic carcinogenesis. Arsenic tends to accumulate in the
      skin. Skin hyperpigmentation and hyperkeratosis have long been known to be the
      hallmark signs of chronic As exposure. There are significant associations between
      these dermatological lesions and risk of skin cancer. The most common arsenic
      induced skin cancers are Bowen's disease (carcinoma in situ), basal cell
      carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's
      disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with
      As-BD are considered for more aggressive cancer screening in the lung and urinary
      bladder. As-BD provides an excellent model for studying the early stages of
      chemical carcinogenesis in human beings. Arsenic exposure is associated with G2/M
      cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and As-BD
      lesions. These cellular abnormalities relate to the p53 dysfunction induced by
      arsenic. The characteristic clinical figures of arsenic-induced skin cancer are:
      (i) occurrence on sun-protected areas of the body; (ii) multiple and recrudescent
      lesions. Both As and UVB are able to induce skin cancer. Arsenic treatment
      enhances the cytotoxicity, mutagenicity and clastogenicity of UV in mammalian
      cells. Both As and UVB induce apoptosis in keratinocytes by caspase-9 and caspase
      8 signaling, respectively. Combined UVB and As treatments resulted in the
      antiproliferative and proapoptotic effects by stimulating both caspase pathways
      in the keratinocytes. UVB irradiation inhibited mutant p53 and ki-67 expression,
      as well as increased in the number of apoptotic cells in As-BD lesions which
      resulted in an inhibitory effect on proliferation. As-UVB interaction provides a
      reasonable explanation for the rare occurrences of arsenical cancer in the sun
      exposed skin. The multiple and recurrent skin lesions are associated with
      cellular immune dysfunction in chronic arsenism. A decrease in peripheral CD4+
      cells was noticed in the inhabitants of arsenic exposure areas. There was a
      decrease in the number of Langerhans cells in As-BD lesion which results in an
      impaired immune function on the lesional sites. Since CD4+ cells are the target
      cell affected by As, the interaction between CD4+ cells and epidermal
      keratinocytes under As affection might be closely linked to the pathogenesis of
      multiple occurrence of arsenic-induced skin cancer. In this review, we provide
      and discuss the pathomechanisms of arsenic skin cancer and the relationship to
      its characteristic figures. Such information is critical for understanding the
      molecular mechanism for arsenic carcinogenesis in other internal organs.

PMID- 16807665
TI  - Falciform ligament in the management of the residual cavity for liver
      hydatidosis: new surgical technique.
AB  - INTRODUCTION: Hydatid disease is a common condition worldwide and continues to be
      a significant societal problem in many countries of all continents. Alhough other
      treatment options are also available, surgery remains the cornerstone of therapy
      for hepatic hydatid disease. Omentoplasty seems to be an efficient technique for
      managing the residual cavity, but it has some shortcomings and might be difficult
      in secondary cases. Therefore we describe a new technique using the falciform
      ligament as a flap instead of omentum for managing the residual cavity, as it is
      more anatomic and a better option for liver cysts. METHODS: From April 2004 to
      October 2005, a total of 20 patients (11 women) with a median age of 43 years
      (range 23-66 years) underwent partial cystectomy-falciformoplasty for hydatid
      liver disease. The falciform ligament was prepared as a flap in all patients
      during the initial step of the operation and, after partial cystectomy and
      evacuation of the cystic components, the flap was inserted into the cystic cavity
      and fixed with sutures. A single drain was inserted into the subhepatic area.
      RESULTS: Cysts were located in the right lobe of the liver in 14 patients and
      mean diameter of the cyst was 10 cm (range 7-25 cm). The mean duration of the
      operation was 40 minutes (range 35-69 minutes), and the mean postoperative
      hospital stay was 4 days (range 3-7 days). None of the patients had any major
      complications. Only two patients had persistent drainage for 7 days, which
      stopped spontaneously. The median follow-up was 9 months (range 2-19 months).
      Patients underwent duplex ultrasonography (US) to check the viability of the flap
      and the residual cavity at 1 week, 1 month, and 3 months postoperatively. US did
      not reveal any collection, the cavities were fully collapsed, and blood flow to
      the falciform ligaments was seen to be viable. CONCLUSIONS: Using the falciform
      ligament as a flap for management of the residual cavity is an easy, safe,
      effective new technique with few complications. It might be a good choice in
      patients with hydatid liver disease.

PMID- 16807666
TI  - Surgical correction of the overgrown columellar labial junction: complementary
      method.
AB  - The overgrown columellar labial junction remains a controversial and neglected
      aspect of rhinoplasty. The authors encountered this problem in a large number of
      their patients and found that routine techniques were not sufficient to correct
      it. They therefore developed a complementary method in rhinoplasty that is safe
      and easy to handle, with long-lasting, satisfactory results for both the patient
      and the surgeon. This method has provided not only better stability on the
      columellar base, but also good aesthetic results. The study involved 43
      rhinoplasty patients with a follow-up period of approximately 1.5 years. This
      report analyzes the surgical anatomy related to the overgrown columellar labial
      junction. Pre- and postoperative aspects of cases involving overgrown columellar
      labial junctions and surgical procedures are discussed.

PMID- 16807667
TI  - A new method for correcting type I and type II constricted (cup and lop) ears.
AB  - Tanzer suggested the term "constricted ear," denoting a spectrum of deformities
      limited to the superior third of the ear. Tanzer classified the constricted ear
      into three types. Type I ears have involvement of the helix, which usually is
      flattened. Type II ears show involvement of both the helix and the scapha. With
      type III ears, the auricle is rolled into a nearly tubular form that some authors
      regard as a form of microtia. The authors' new method for correcting the
      constricted ear varies in accordance with the diverse degree of deformity. The
      new method was used to correct constricted ears through a one-stage operation in
      eight type I cases. For the remaining six type 2 cases, the methods were combined
      with composite grafting. Most of the patients were satisfied with the final
      results. Therefore, the authors conclude that their approach is suitable for the
      treatment of type I and type II constricted ears.

PMID- 16807668
TI  - Subtotal ear reconstruction for correction of type 3 constricted ears.
AB  - Constricted ears are characterized by four features: (a) lop deformity, (b)
      protrusion, (c) low ear position, and (d) decreased ear size. These deformities,
      resulting from inadequate length of the helix, have been described by Tanzer
      (1975) as a purse-string closure of the ear. Constricted ears are classified into
      types 1, 2, and 3 according to the severity of the deformity. Type 3 constricted
      ear, the most severe, with decreased size and loss of the upper half of the
      normal ear contour, is classified currently as a mild form of microtia.
      Therefore, autogenous rib cartilage was used to reconstruct the affected ear much
      as in correction of microtia. The expanded skin flap in the mastoid area was used
      to reconstruct auricles for 14 patients with type 3 constricted ear in the
      authors' center from 2001 to 2004. All the patients were satisfied with the final
      results. Therefore, the authors conclude that their operative technique is
      practical and reliable.

PMID- 16807669
TI  - Lack of effect of corticosteroid injection at the shoulder joint on blood glucose
      levels in diabetic patients.
AB  - The effect of systemic glucocorticosteroids on the metabolism of glucose is well
      known; however, there are no reports on the effect of intraarticular steroids on
      the metabolism of glucose in diabetic patients. Controlled or near controlled
      diabetic patients who have self-monitoring devices for home monitoring of blood
      glucose with shoulder pain were offered an intraarticular crystalloid steroid
      injection of 35 mg of methylprednisolone acetate (MPA) at the shoulder joint
      after failure of pharmacological and physical therapy. Patients were asked to
      record blood glucose levels before and 2 h after breakfast, lunch, and supper
      (six times a day) every other day during 1 week before the injection and during
      the day of the injection, the next day and every other day for 2 weeks after the
      injection. Fructosamine levels were obtained just before the injection and 2
      weeks after the injection. Wilcoxon signed rank test was used to compare the mean
      glucose levels before with those after the injection. Paired t test was used to
      compare the mean fructosamine values after the injection with those before the
      injection. Eighteen patients completed the study. Fifteen had adhesive
      capsulitis. The mean glucose levels before injection were 165.5, 195.5, 184.6,
      199.4, 182.8, and 200.7 mg% before and 2 h after breakfast, lunch, and supper,
      respectively. There was no significant change between the mean glucose values
      before and after meals after the injection compared to those before the
      injection, respectively, except on a few occasions only throughout the study
      period. Mean fructosamine level before injection was 279 micromol/l+/-49.8
      compared to 275 micromol/l+/-50.9 after the injection (P=0.125). Intraarticular
      injection of MPA at the shoulder joint in diabetic patients with shoulder pain
      has no significant effect on blood glucose levels.

PMID- 16807670
TI  - From molecular mimicry to cross-reactivity or pathogen expansion? A hypothesis.
AB  - Very recently, several studies have convincingly demonstrated the role of
      infection in the development of the antiphospholipid syndrome. Cross antibody
      mediated reactivity due to molecular mimicry between endothelial glycoproteins
      and microbial products was considered as an important pathogenic mechanism.
      However, another consequence of the molecular mimicry may be proposed. Similar
      tissues have less likelihood of being rejected and have a greater chance of being
      accepted by the host. According to this principle, pathogens with common-to-host
      antigens may attach readily and not be eliminated. A direct expansion of such
      pathogens may involve new territories. The targets of the approach 1, "from
      molecular mimicry to cross-reactivity," are T-B cells system inhibition
      modulation. The targets of approach 2, "from molecular mimicry to pathogen
      expansion," are pathogens, enforcement of barriers, elimination techniques, and
      preventive strategy.

PMID- 16807671
TI  - Prognostic impact of Thomsen-Friedenreich tumor antigen and disseminated tumor
      cells in the bone marrow of breast cancer patients.
AB  - PURPOSE: The Thomsen-Friedenreich antigen (TF, CD176) is a specific oncofetal
      carbohydrate epitope (Gal beta1-3GalNAc alpha-O-Ser/Thr) expressed on the surface
      of various carcinomas. It mediates endothelium adhesion and formation of
      metastases. As it also causes immune response, its prognostic impact is
      indeterminate. The presence of disseminated tumor cells in the bone marrow of
      breast cancer patients (DTC-BM) indicates worse prognosis. We examined the
      expression of TF in primary breast cancer tissue of 265 patients with known BM
      status at the time of first diagnosis. METHODS: BM aspiration, cytospin
      preparation and immunocytochemical staining with the anti-Cytokeratin antibody
      A45 B/B3 was done following a standardised protocol. TF expression was examined
      immunohistochemically on Tissue Micro Arrays (TMA) with the anti-TF antibody A78
      G/A7. Evaluation was done using the immunoreactive score (IRS). RESULTS: Median
      IRS for TF expression was 2 (0-12). 68 of 265 patients (25.7%) showed DTC-BM with
      a median of 2/2 x 10(6) cells (1-1500). There was no correlation between TF
      expression and DTC-BM. After a median follow up of 60.1 months (7-119), the
      detection of DTC-BM showed prognostic significance for overall survival (OS, p =
      0.034), whereas TF positivity (IRS > 2) indicated prolonged disease-free (p =
      0.01), distant disease-free (p = 0.005), and overall survival (p = 0.005).
      DISCUSSION: Patients with TF-positive tumors had a significantly better
      prognosis. Dissemination routes, TF-mediated metastasis formation, and the
      immunogeneity of TF might determine the prognostic impact of TF expression in
      different tumor entities. Further characterisation of primary tumors and DTC-BM
      could help to improve the biological understanding of metastases and develop
      targeted therapies.

PMID- 16807672
TI  - Fulvestrant in advanced male breast cancer.

PMID- 16807673
TI  - Polymorphisms in the KDR and POSTN genes: association with breast cancer
      susceptibility and prognosis.
AB  - Angiogenesis is an important step in the development of cancer. Vascular
      endothelial growth factor is a major regulator of breast cancer angiogenesis, the
      effects of which are transmitted through the kinase domain receptor (KDR). Up
      regulation of KDR by periostin (POSTN) induces angiogenesis. We screened the KDR
      and the POSTN genes for published single nucleotide polymorphisms (SNPs) and
      chose two SNPs in each gene for further analyses. We carried out a case-control
      study consisting of 412 familial and 912 unselected breast cancer cases together
      with ethnically and geographically selected controls. Genotype, haplotype and
      genotype combination analyses were carried out to evaluate their effect on
      susceptibility to and prognosis of breast cancer. A haplotype in the POSTN gene
      was associated with an increased risk even after correction for multiple
      comparisons. Nominal associations between the SNPs and prognostic indicators were
      also observed. Tumors of the KDR 472His allele carriers were less often
      progesterone receptor negative according to both genotype and haplotype analyses
      (OR 0.61, 95%CI 0.40-0.92 and OR 0.60, 95%CI 0.40-0.91, respectively). The POSTN 
      33G allele carriers had more often high grade and estrogen receptor negative
      tumors (OR 1.75, 95%CI 1.02-3.01 and OR 1.70, 95%CI 1.04-2.78, respectively). The
      overall and cancer specific survival after 15 years of follow-up was more than
      75%, and it did not depend on the genotype. Although a major effect of the SNPs
      in the KDR and the POSTN genes on breast cancer susceptibility and prognosis was
      excluded, the effect of the POSTN C-33G SNP on prognosis needs further
      characterization.

PMID- 16807674
TI  - A study on the association of cytochrome-P450 1A1 polymorphism and breast cancer
      risk in north Indian women.
AB  - Cytochrome P-450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogens and
      mammary carcinogens into 2-hydroxy catechol metabolites. Many commonly occurring
      single nucleotide polymorphism (SNP) are reported in CYP1A1 in various
      populations that include, isoleucine to valine substitution at 462 codon in heme
      binding region in exon 7 (A to G transition at position 2455; M2), threonine to
      asparagine substitution at codon 461 (C to A transversion at position 2453; M4),
      T to C transition at 3801 position (M1) and T to C transition at position 3205
      (M3) in 3' non-coding region. Epidemiological studies have shown inconsistent
      patterns between CYP1A1 polymorphism and breast cancer risk among various
      populations. Most of the studies have shown significant association between
      CYP1A1 genotype polymorphism and breast cancer risk. The present investigation
      was therefore undertaken to investigate the association of M1, M2, M3 and M4
      polymorphisms and their subsequent contribution in premenopausal and
      postmenopausal women with breast cancer risk in north Indian women. Genomic DNA
      was isolated from case controls and breast cancer patients, specific segments of
      genomic DNA were amplified and restriction fragment length polymorphism (RFLP)
      was performed. CYP1A1 expression and catalytic activity were also assessed in
      premenopausal and postmenopausal case controls and patients. Polymorphism at M1,
      M2 and M4 alleles was detected and odds ratio for W/M1 and M1/M1 was calculated
      as 1.07 (95% CI, 0.59-1.87) and 0.74 (95% CI, 0.28-1.96) respectively. Odds ratio
      for W/M1 and M1/M1 alleles in premenopausal and postmenopausal women was 1.09
      (95% CI, 0.45-2.49)/0.62 (95% CI, 0.10-2.66) and 1.60 (95% CI, 0.60-4.22)/1.06
      (95% CI, 0.22-7.33) respectively. Odds ratio for W/M4 and M4/M4 allele was 1.20
      (95% CI, 0.65-2.24)/4.55 (95% CI, 0.44-226.2) and 0.96 (95% CI, 0.36-2.64)/4.51
      (95% CI, 0.23-273.0) respectively in total and premenopausal women. In
      postmenopausal women odds ratio was calculated as 1.16 (95% CI, 0.45-2.94) for
      M4/W but it could not be detected for M4/M4 since this genotype was not found in
      any postmenopausal case controls. Odds ratio for W/M2 genotype was calculated
      0.57 (95% CI, 0.28-1.02), 1.06 (95% CI, 0.40-2.47) and 0.33 (95% CI, 0.12-0.89)
      respectively for total, premenopausal and postmenopausal women, however, in any
      group the odds ratio for M2/M2 could not be detected as M2/M2 genotype was not
      found in breast cancer patients. Polymorphism at M1 and M4 alleles was not found
      significantly associated with breast cancer risk and only wild type genotype was
      found in case controls and patients for M3 allele. Lack of protective association
      between CYP1A1 M2 genotype was also observed, however, in postmenopausal women a
      significant protective association with breast cancer risk was found (odds ratio,
      0.33; 95% CI, 0.12-0.89; P-value 0.03). Similarly, no significant alteration in
      CYP1A1 expression and catalytic activity was observed in wild type and variant
      genotypes both in premenopausal and postmenopausal patients as compared with
      their respective controls. The results obtained from the present investigation
      thus suggest that probably CYP1A1 (M1, M2, M3, and M4) polymorphism alone does
      not play a significant role in the breast cancer risk in north Indian women.

PMID- 16807675
TI  - Direct-to-patient BRCA1 testing: the Twoj Styl experience.
AB  - Ideally, a genetic screening program for cancer should offer testing to all women
      who qualify, and who wish to participate, and who might benefit from the test. As
      the number of preventive options for women at high risk for hereditary breast
      cancer expands, the demand for testing increases. However, many women do not have
      ready access to testing because of cost, and many others have not been recognized
      by their physicians to be candidates for testing. It is possible to increase
      women's awareness about hereditary cancer through the popular press. Genetic
      testing was offered to 5000 Polish women through an announcement placed in a
      popular women's magazine (Twoj Styl) in October 2001. A total of 5024 women who
      qualified received a free genetic test for three mutations in BRCA1 which are
      common in Poland. Out of these, 198 women (3.9%) were found to carry a BRCA1
      mutation. The overall cost per mutation detected was 630 US dollars-
      approximately 50-100 times less than the equivalent cost in North America.
      Genetic counseling was offered to women with a positive test or with a
      significant family history of breast or ovarian cancer. The great majority of
      women who took part in the program expressed a high degree of satisfaction and
      after one year approximately two-thirds of identified mutation carriers had
      complied with our recommendations for breast cancer screening. We found this
      model of genetic testing and delivery of genetic information to be very efficient
      in a population in which founder mutations predominate. There is a need for
      similar studies in other populations.

PMID- 16807676
TI  - A high risk of occurrence of sporadic breast cancer in individuals with the 104NN
      polymorphism of the COL18A1 gene.
AB  - We investigated the influence of the polymorphism D104N of the COL18A1 gene,
      encoding endostatin, on the occurrence of sporadic breast cancer in 181 patients
      and 448 controls. The homozygous 104NN polymorphism was found in five patients
      but was absent in controls (2.8% vs 0.0%; P = 0.002). Individuals with this
      genotype had a significantly increased risk for disease. Our results suggest, for
      the first time, that the homozygous 104NN polymorphism, even at low frequency,
      constitutes an important inherited determinant of the disease.

PMID- 16807677
TI  - Lack of association between NOS3 Glu298Asp and breast cancer risk: a case-control
      study.
AB  - Nitric oxide (NO) plays a central role in the physiololgy and pathology of
      diverse tissues. Different studies provide data suggesting that the endothelial
      cell nitric oxide synthase (NOS3) expression in peritumoral microvessels might be
      a prognostic indicator in breast cancer patients. However, the putative
      contribution of common NOS3 germline variants to breast cancer risk remained
      unknown. A recent work comprising 269 breast cancer patients and 244 controls
      suggested that NOS3 Glu298Asp polymorphism is associated to breast cancer risk
      (OR=1.9). We performed an independent analysis of these results in 440 unrelated
      patients and 321 controls from Spanish population. Although our study was 90%
      powered to detect ORs >/=1.55, did not find any significant difference in the
      Glu298Asp allele distribution between cases and controls (P > 0.42). These
      putative reasons for this result are discussed.

PMID- 16807678
TI  - Proteasome inhibitors induce a p38 mitogen-activated protein kinase (MAPK)
      dependent anti-apoptotic program involving MAPK phosphatase-1 and Akt in models
      of breast cancer.
AB  - Proteasome inhibitors represent a novel class of anti-tumor agents that have
      clinical efficacy against hematologic malignancies, but single-agent activity
      against solid tumors such as breast cancer has been disappointing, perhaps due to
      activation of anti-apoptotic survival signals. To evaluate a possible role for
      the p38 mitogen-activated protein kinase (MAPK), A1N4-myc human mammary
      epithelial, and BT-474 and MDA-MB-231 breast carcinoma cells, were studied.
      Exposure of these lines to pharmacologic p38 blockade enhanced proteasome
      inhibitor-mediated apoptosis, as did overexpression of dominant negative (DN)-p38
      alpha and -beta-MAPK isoforms. Inhibition of p38 resulted in suppression of
      induction of anti-apoptotic MAPK phosphatase (MKP)-1, in association with
      enhanced activation of the pro-apoptotic c-Jun-N-terminal kinase (JNK). Moreover,
      infection of cells treated with a proteasome inhibitor/p38 inhibitor combination
      with Adenovirus (Ad) inducing over-expression of MKP-1 suppressed apoptosis
      compared with controls. Further targets of p38 MAPK were also studied, and
      proteasome inhibition activated phosphorylation of MAPK-activated protein kinase
      2, heat shock protein (HSP)-27, and the AKT8 virus oncogene cellular homolog
      (Akt). Inhibition of p38 MAPK resulted in decreased phospho-HSP-27 and phospho
      Akt, while down-regulation of HSP-27 with a small interfering RNA decreased
      phosphorylation of Akt, directly linking activation of p38 to Akt. Finally,
      inhibition of Akt with phosphatidylinositol-3-kinase inhibitors increased
      apoptosis, as did over-expression of DN-Akt. These studies support the hypothesis
      that proteasome inhibitors activate an anti-apoptotic survival program through
      p38 MAPK that involves MKP-1 and Akt. Further, they suggest that strategies
      targeting MKP-1 and Akt could enhance the anti-tumor efficacy of proteasome
      inhibitors against breast cancer.

PMID- 16807679
TI  - Dural arteriovenous fistulas of the cavernous sinus with onset of intracerebral
      haemorrhage mimicking hypertensive putaminal hemorrhage.
AB  - We describe a patient with dural arteriovenous fistulas of the cavernous sinus
      (CS-dAVFs) who developed an intracerebral haemorrhage (ICH) mimicking
      hypertensive putaminal haemorrhage. Drainage into the superior ophthalmic vein
      (SOV) and inferior petrosal sinus (IPS) was not demonstrated on cerebral
      angiography, and only cortical venous reflux into the Sylvian vein was observed.
      In cases of venous drainage concentrated on the Sylvian vein, CS-dAVFs could
      indicate ICH with radiological appearance resembling putaminal haemorrhage.

PMID- 16807682
TI  - Gene expression profiles during heat acclimation in Arabidopsis thaliana
      suspension-culture cells.
AB  - Thermotolerance is induced by moderated heat acclimation. Suspension cultures of
      heat-acclimated Arabidopsis thaliana L. (Heynh.), ecotype Columbia, show
      thermotolerance against lethal heat shock (9 min, 50 degrees C), as evidenced by
      a chlorophyll assay and fluorescein diacetate staining. To monitor the genome
      wide transcriptome changes induced by heat acclimation at 37 degrees C, we
      constructed an A. thaliana cDNA microarray containing 7,989 unique genes, and
      applied it to A. thaliana suspension-culture cells harvested at various times
      (0.5, 1, 2.5, 6, and 16 h) during heat acclimation. Data analysis revealed 165
      differentially expressed genes that were grouped into ten clusters. We compared
      these genes with published and publicly available microarray heat-stress-related
      data sets in AtGenExpress. Heat-shock proteins were strongly expressed, as
      previously reported, and we found several of the up-regulated genes encoded
      detoxification and regulatory proteins. Moreover, the transcriptional induction
      of DREB2 (dehydration responsive element-binding factor 2) subfamily genes and
      COR47/rd17 under heat stress suggested cross-talk between the signaling pathways
      for heat and dehydration responses.

PMID- 16807683
TI  - Muscle architecture of the common chimpanzee (Pan troglodytes): perspectives for
      investigating chimpanzee behavior.
AB  - Thorpe et al. (Am J Phys Anthropol 110:179-199, 1999) quantified chimpanzee (Pan
      troglodytes) muscle architecture and joint moment arms to determine whether they
      functionally compensated for structural differences between chimpanzees and
      humans. They observed enough distinction to conclude that musculoskeletal
      properties were not compensatory and suggested that chimpanzees and humans do not
      exhibit dynamically similar movements. These investigators based their assessment
      on unilateral limb musculatures from three male chimpanzees, of which they called
      one non-adult representative. Factors such as age, sex, and behavioral
      lateralization may be responsible for variation in chimpanzee muscle
      architecture, but this is presently unknown. While the full extent of variation
      in chimpanzee muscle architecture due to such factors cannot be evaluated with
      data presently available, the present study expands the chimpanzee dataset and
      provides a preliminary glimpse of the potential relevance of these factors.
      Thirty-seven forelimb and 36 hind limb muscles were assessed in two chimpanzee
      cadavers: one unilaterally (right limbs), and one bilaterally. Mass, fiber
      length, and physiological cross-sectional area (PCSA) are reported for individual
      muscles and muscle groups. The musculature of an adult female is more similar in
      architectural patterns to a young male chimpanzee than to humans, particularly
      when comparing muscle groups. Age- and sex-related intraspecific differences do
      not obscure chimpanzee-human interspecific differences. Side asymmetry in one
      chimpanzee, despite consistent forelimb directional asymmetry, also does not
      exceed the magnitude of chimpanzee-human differences. Left forelimb muscles, on
      average, usually had higher masses and longer fiber lengths than right, while
      right forelimb muscles, on average, usually had greater PCSAs than left. Most
      muscle groups from the left forelimb exhibited greater masses than right groups,
      but group asymmetry was significant only for the manual digital muscles. The hind
      limb exhibited less asymmetry than the forelimb in most comparisons. Examination
      of additional chimpanzees would clarify the full range of inter- and intra
      individual variation.

PMID- 16807685
TI  - Antidepressants and suicidality.

PMID- 16807684
TI  - Phosphoproteomic analysis of the human pituitary.
AB  - The pituitary is the central endocrine gland that regulates the functions of
      various target organs in the human body. Because of the pivotal regulatory role
      of the pituitary, it is essential to define on a global scale the components of
      the pituitary protein machinery, including a comprehensive characterization of
      the post-translational modifications of the pituitary proteins. Of particular
      interest is the examination of the phosphorylation status of the pituitary in
      health and disease. Towards the goal of global profiling of pituitary protein
      phosphorylation, we report here the application of the in-gel IEF-LC-MS/MS
      approach to the study of the pituitary phosphoproteome. The analytical strategy
      combined isoelectric focusing in immobilized pH gradient strips with immobilized
      metal ion affinity chromatography and mass spectrometry. With this method, a
      total of 50 phosphorylation sites were characterized in 26 proteins. Because the
      investigation involved primary tissue, the findings provide a direct glimpse into
      the phosphoprotein machinery operating within the human pituitary tissue
      microenvironment.

PMID- 16807687
TI  - Bilateral compressive lumbosacral plexopathy due to internal iliac artery
      aneurysms.

PMID- 16807688
TI  - Effectiveness of a prolonged compression of scalp arteries on migraine attacks.

PMID- 16807686
TI  - Single gene disorders causing ischaemic stroke.
AB  - Stroke is the third most common cause of death and the leading cause of long-term
      neurological disability in the world. Conventional vascular risk factors for
      stroke contribute approximately to only forty to fifty percent of stroke risk.
      Genetic factors may therefore contribute to a significant proportion of stroke
      and may be polygenic, monogenic or multi-factorial. Monogenic (single gene)
      disorders may potentially account for approximately one percent of all ischaemic
      stroke. Monogenic stroke disorders include conditions such as cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts
      and leukoencephalopathy (CARASIL) and hereditary endotheliopathy, retinopathy,
      nephropathy and stroke (HERNS). In addition, other monogenic conditions such as
      sickle cell and Fabry disease also lead to stroke. These monogenic disorders
      cause either small vessel or large vessel stroke (or a combination of both) and
      serve as useful models for understanding and studying conventional stroke and
      cerebrovascular disease and its accompaniments such as vascular dementia.

PMID- 16807689
TI  - Joseph Jules Dejerine (1849-1917).

PMID- 16807693
TI  - Extract of the bristles of Dirphia sp. increases nitric oxide in a rat pleurisy
      model.
AB  - OBJECTIVES: In the present study we assessed the inflammatory potential of venom
      obtained from caterpillar genus Dirphia in an acute model of lung injury.
      MATERIAL AND METHODS: Injection of extract from the bristles of Dirphia sp. (EBD)
      into the pleural cavity of rats elicited an acute inflammation response
      characterized by fluid accumulation which contained a large number of
      polymorphonuclear neutrophils (PMNs). RESULTS: The results show that EBD induces
      an inflammatory response, with a significant increase in PMNs, exudate and nitric
      oxide within 4 h after a 0.04 mg/kg dose. The administration of anti-inflammatory
      drugs (fructose-1,6-bisphosphate, dexamethasone, rofecoxib, sodium diclofenac and
      pyrilamine) significantly reduced the inflammatory effect of EBD. CONCLUSIONS:
      EBD causes an inflammatory reaction in the pleural cavity of rats involving a
      variety of inflammatory mediators, its action mechanism probably involving
      cellular injury and the exacerbated induction of cytokines and nitric oxide.

PMID- 16807694
TI  - Organ specific apoptosis following polymicrobial intraperitoneal infection.
AB  - BACKGROUND: Leukocyte apoptosis allows safe removal of potentially harmful cells
      and facilitates resolution of inflammation. We hypothesized that the number of
      apoptotic cells changes in a disproportionate fashion in parenchymal organs in
      response to intra-abdominal infection. MATERIALS AND METHODS: The percentage of
      apoptotic cells in the liver, spleen, lung, and peripheral blood was evaluated
      following cecal ligation and puncture (CLP) in mice. Tissue myeloperoxidase (MPO)
      levels were measured as an index of neutrophil extravasation. RESULTS: Liver &
      spleen MPO continually increased, while lung MPO remained low after CLP. In
      parallel to the increase in MPO, liver & spleen apoptosis continually increased
      throughout the 9-day follow-up period, whereas lung apoptosis remained unchanged.
      CONCLUSIONS: The distribution of apoptotic cells during intraperitoneal infection
      occurs in an organ specific manner, with significant increases in the spleen and
      liver. This distribution likely reflected the clearance of apoptotic cells as the
      inflammatory focus became contained.

PMID- 16807696
TI  - Peripheral blood mononuclear cell responses to heat shock proteins and their
      derived synthetic peptides in juvenile idiopathic arthritis patients.
AB  - BACKGROUND: Sequence homology and cross reactivity between microbial and human
      heat shock proteins (hsps) led to the concept that hsps might be involved in the
      etiopathogenesis of autoimmune diseases. OBJECTIVE: In our study we stimulated
      peripheral blood mononuclear cells (PBMC) of patients with juvenile idiopathic
      arthritis (JIA) and healthy controls with various hsp-derived peptides together
      with the whole molecules of corresponding hsp. METHODS: PBMC were cultured with
      recombinant human hsp60 (rh-hsp60), rh-hsp70, Mycobacterium bovis hsp65 (M.bovis
      hsp65), P562-571 human hsp60, P180-188 M. bovis hsp65, P450-463 human hsp70 and
      P545-554 cytokeratin derived synthetic peptides. Cell responses were measured
      after incorporation of (3)H-thymidine and expressed as stimulation indices.
      RESULTS AND CONCLUSION: We found elevated proliferative response to rh-hsp60, M.
      bovis hsp65 and P562-571 human hsp60 derived peptide in patients with JIA
      polyarthritis. Significantly elevated proliferation to P180-188 M. bovis hsp65
      was found in JIA lasting more than 2 years. None of the particular clinical
      characteristics (RF, ANA, HLA B27 and disease activity) seemed to be associated
      with hsp or hsp-derived synthetic peptide proliferative response in the JIA
      cohort.

PMID- 16807695
TI  - The differential effects of low dose and high dose concanavalin A on cytokine
      profile and their importance in liver injury.
AB  - OBJECTIVE: Intravenous injection of concanavalin A (Con A) can cause mice to
      suffer from acute liver failure in a dose dependent manner and little is known
      about the difference between the high dose and the low dose of Con A regarding
      the immune response they initiate. The aim of this study was to analyze whether
      differential effects exist between the low dose and high dose of concanavalin A
      on the intrahepatic immune system and their importance in the development of
      liver injury. MATERIALS AND METHODS: A high dose of Con A (15 microg/g) was
      injected intravenously to induce murine hepatitis. A low dose of Con A (3
      microg/g) was injected intravenously 12 h before the injection of the high dose
      of Con A (15 microg/g). Liver injury was evaluated by serum transaminase assay
      and H&E staining. Serum cytokine concentrations were determined by enzyme-linked
      immunosorbent assay (ELISA), intrahepatic cytokine and Fas mRNA levels by reverse
      transcriptase polymerase chain reaction. Intracellular cytokine expression and
      FasL expression were analyzed by flow cytometry and Fas protein expression in
      hepatocytes by Western-blotting. Intrahepatic apoptosis was evaluated by terminal
      deoxynucleotidyl transferase mediated nick end labeling (TUNEL). RESULTS: Low
      dose Con A injection induced a distinct cytokine expression profile,
      characterized by a preferentially elevated serum IL-6 at the early stage of
      stimulation, whereas high dose Con A injection provoked significant elevation of
      various cytokines involved in Con A-induced hepatitis. Pretreatment with a low,
      nonhepatoxic dose of Con A (3 microg/g) significantly decreased production of
      proinflammatory cytokines induced by the high dose Con A (15 microg/g).
      Furthermore, low dose Con A pretreatment could significantly decrease the serum
      levels of transaminases and liver necrosis induced by high dose of Con A. The
      intrahepatic Fas expression was also apparently reduced, accompanied by a
      decrease in hepatocyte apoptosis. CONCLUSION: Low dose Con A stimulation induced
      a different cytokine profile from high dose Con A stimulation resulting in
      differential importance in the development of liver injury.

PMID- 16807697
TI  - The cervical lymph node preparation: a novel approach to study lymphocyte homing
      by intravital microscopy.
AB  - OBJECTIVE: Lymphocyte recirculation constitutes an integral part of the adaptive
      immune system. Blood-borne lymphocytes migrate into secondary lymphoid organs,
      crossing the vascular wall of site-specific high endothelial venules (HEVs). We
      created a preparation of the cervical lymph node in mice to study lymphocyte
      homing in vivo. METHODS AND RESULTS: Our novel approach allowed the detailed
      analysis of hemodynamics and lymphocyte-HEV endothelium interactions by means of
      intravital fluorescence microscopy. We confirm the key roles of L-selectin and
      LFA-1 for lymphocyte homing. Blockade of L-selectin function inhibited lymphocyte
      rolling and firm adhesion by 92% and 66%. In LFA-1-deficient mice, lymphocyte
      firm adhesion was reduced by 70%. In addition to the microcirculation studies,
      the cervical lymph node preparation allowed for visualization of afferent
      lymphatic transport, which is mainly derived from the oral mucosa. CONCLUSION:
      This study reports a novel technical tool for the detailed in vivo analysis of
      adaptive immune responses.

PMID- 16807698
TI  - The antioxidants curcumin and quercetin inhibit inflammatory processes associated
      with arthritis.
AB  - OBJECTIVE: Curcumin and quercetin are antioxidant molecules with anti
      proliferative, anti-inflammatory and immunosuppressive activities. The objective
      of this study was to investigate the inhibitory activity of these agents using
      four assays of inflammatory aspects of arthritis. METHODS: Crystal-induced
      neutrophil activation was measured by luminol-dependent chemiluminescence.
      Synoviocyte proliferation was measured by an MTS assay using HIG-82 rabbit
      synoviocytes in cell culture. Chondrocyte (cultured primary cells) expression of
      the matrix metalloproteinases collagenase and stromelysin was measured by
      Northern Blot analysis. Angiogenesis was measured using the chorioallantoic
      membrane of the chick embryo. RESULTS: Both agents inhibited neutrophil
      activation, synoviocyte proliferation and angiogenesis. Curcumin strongly
      inhibited collagenase and stromelysin expression at micromolar concentrations
      whereas quercetin had no effect in this assay. CONCLUSION: These studies suggest
      that curcumin and to a lesser extent quercetin may offer therapeutic potential
      for the treatment of crystal-induced arthritis or rheumatoid arthritis.

PMID- 16807699
TI  - Orthodontic springs and auxiliary appliances: assessment of magnetic field
      interactions associated with 1.5 T and 3 T magnetic resonance systems.
AB  - The objective of this paper is to evaluate magnetic field interactions at 1.5 and
      3 T for 20 orthodontic devices used for fixed orthodontic therapy. Twenty springs
      and auxiliary parts made from varying ferromagnetic alloys were tested for
      magnetic field interactions in the static magnetic field at 1.5 and 3 T. Magnetic
      translational force F(z) (in millinewtons) was evaluated by determining the
      deflection angle beta [American Society for Testing and Materials (ASTM standard
      test method)]. Magnetic-field-induced rotational force F(rot) was qualitatively
      determined using a five-point scale. beta was found to be >45 degrees in 13(15)
      devices at 1.5(3) T and translational force F(z) exceeded gravitational force
      F(g) on the particular object [F(z) 10.17-261.4 mN (10.72-566.4 mN) at 1.5(3) T].
      F(z) was found to be up to 24.1(47.5)-fold higher than F(g) at 1.5(3) T.
      Corresponding to this, F(rot) on the objects was shown to be high at both field
      strengths (> or = +3). Three objects (at 1.5 T) and one object (at 3 T) showed
      deflection angles <45 degrees , but F(rot) was found to be > or = +3 at both
      field strengths. For the remaining objects, beta was below 45 degrees and torque
      measurements ranged from 0 to +2. Of 20 objects investigated for magnetic field
      interactions at 1.5(3) T, 13(15) were unsafe in magnetic resonance (MR), based on
      the ASTM criteria of F(z). The implications of these results for orthodontic
      patients undergoing MRI are discussed.

PMID- 16807700
TI  - Giant cell tumors of the tendon sheath may present radiologically as intrinsic
      osseous lesions.
AB  - The purpose of this study was to explain radiographic features of giant cell
      tumors of the tendon sheath (GCTTS), in particular, osseous extension, by
      correlating imaging findings with histology in order to increase the accuracy of
      radiological diagnosis. In a series of 200 consecutive osseous (pseudo) tumors of
      the hand, on radiography, six patients presented with an intrinsic osseous lesion
      caused by a histologically confirmed neighboring GCTTS. Available radiographs,
      computed tomography (CT), and contrast-enhanced magnetic resonance (MR) images
      were correlated with histology. Radiography showed osseous lesions consisting of
      well-defined cortical defects in four (one of whom also demonstrated cortical
      scalloping) and a slightly expansile, well-defined osteolytic lesion in two
      patients. MR obtained in four patients showed the extraosseous tumor
      invading/eroding bone and causing cortical scalloping (three and one patients,
      respectively). Extension depicted on MR was confirmed on the two available
      resection specimens. All lesions were polylobular (cauliflower or mushroom like)
      and neighboring tendon sheaths. Dense collagen and hemosiderin-loaded macrophages
      explained the high CT attenuation and the low MR signal intensity on T2-weighted
      images that was observed in all four MR and in all two CT scans. The high density
      of proliferative capillaries explained the marked enhancement observed in all
      four patients with gadolinium (Gd)-chelate-enhanced MR imaging. GCTTS is a soft
      tissue (pseudo) tumor that may invade bone and as a consequence mimick an
      intrinsic osseous lesion on radiographs. In such cases, specific MR and CT
      features that can be explained by histological findings can be used to suggest
      the correct diagnosis.

PMID- 16807701
TI  - Ethnical differences in HLA-II genotyping results of North-Eastern Polish
      ulcerative colitis patients.

PMID- 16807702
TI  - Preparation of a novel composite particles and its application in the fluorescent
      detection of proteins.
AB  - A new fluorescence method for the detection of proteins with novel composite
      nanoparticles (CdS/PPA) has been developed. The composite nanoparticles have been
      prepared through an in-situ polymerization method under ultrasonic irradiation.
      The surface of the composite nanoparticles was covered with functional groups (
      COOH). These groups may play a major role in the improving the water solubility
      and biocompatibility of the nanoparticles. The composite particles is combined
      with proteins in NaAc-HCl buffer solution (pH=1.99), which can result in strong
      fluorescence, and the response is linearly proportional to the concentration of
      proteins. In lambdaem/lambdaex=650 nm/365 nm place (the stoke' shift is 285 nm),
      its fluorescent strength reaches the maximum. Under the optimum conditions, the
      linear range is 0.10-20.0 microg.ml(-1) with the detection limit of 41 ng.ml(-1)
      for HSA, and 0.10-15.0 microg.ml(-1) with the detection limit of 35 ng.ml(-1) for
      Human gamma-IgG . The method has been applied to the determination of the total
      protein in human serum samples collected from the hospital and the results are
      satisfactory.

PMID- 16807703
TI  - Biosensors as useful tools for environmental analysis and monitoring.
AB  - Recent advances in the development and application of biosensors for
      environmental analysis and monitoring are reviewed in this article. Several
      examples of biosensors developed for relevant environmental pollutants and
      parameters are briefly overviewed. Special attention is paid to the application
      of biosensors to real environmental samples, taking into consideration aspects
      such as sample pretreatment, matrix effects and validation of biosensor
      measurements. Current trends in biosensor development are also considered and
      commented on in this work. In this context, nanotechnology, miniaturisation,
      multi-sensor array development and, especially, biotechnology arise as fast
      growing areas that will have a marked influence on the development of new
      biosensing strategies in the near future.

PMID- 16807705
TI  - Comment on "The influence of hyperchloraemia on acid--base interpretation in
      diabetic ketoacidosis" by Taylor et al.

PMID- 16807706
TI  - Colonization of the medial lumen is a risk factor for catheter-related
      bloodstream infection.
AB  - OBJECTIVE: To analyze the colonization of each lumen and the risk factors for
      triple-lumen central venous catheter-related bloodstream infection (CRBI). DESIGN
      AND SETTING: Prospective, observational study in the medical-surgical intensive
      care unit (ICU) of a teaching hospital. PATIENTS: A total of 120 patients
      requiring the insertion of a triple-lumen catheter. INTERVENTIONS: Cultures of
      the catheter. MEASUREMENTS AND RESULTS: The catheters were removed when CRBI was
      suspected or at discharge from ICU. At the removal time, blood cultures, a swab
      of the insertion site and a culture of the catheter tip were performed.
      Furthermore, we made quantitative cultures of the proximal, medial and distal
      lumen. We diagnosed CRBI in six patients (3.35 CRBI/1,000 days at risk), and we
      observed that in these patients colonization of the medial lumen was more
      frequent (5/6) than in patients without CRBI (9/114; p = 0.0001). The logistic
      regression analysis showed that colonization of the medial lumen was an
      independent risk factor for CRBI (OR 28.1, 95% CI 2.2-364.9). CONCLUSIONS:
      Colonization of the medial lumen is an independent risk factor for triple-lumen
      catheter-related bloodstream infection, possibly due to the absence of use of
      this lumen.

PMID- 16807707
TI  - Differences in time to positivity can affect the negative predictive value of
      blood cultures drawn through a central venous catheter.

PMID- 16807708
TI  - Long-standing type II diabetes mellitus is not a risk factor for slow gastric
      emptying in critically ill patients.
AB  - OBJECTIVE: Delayed gastric emptying (GE) is common both in critical illness and
      in patients with diabetes mellitus (DM). The effect of DM on the incidence of
      slow GE in these patients is unknown. We evaluated the effect of DM on liquid GE
      in critically ill patients. METHODS: Retrospective analysis of GE using a
      standard [13C]octanoic acid breath test in 12 type 2 DM patients compared with
      (a) 44 critically ill patients without DM, including (b) a subgroup of 15 age-
      and sex-matched patients and (c) 15 healthy volunteers. We determined the gastric
      emptying coefficient (GEC) and the gastric half-emptying time (t50). Mean APACHE
      II scores, blood glucose levels and use of morphine were similar between patient
      groups. RESULTS: GE was faster in critically ill patients with DM (t50 122 +/- 11
      min, GEC: 3.8 +/- 0.3) than in patients without DM (t50 168 +/- 16 min, GEC 2.8
      +/- 0.1) and in age- and sex-matched controls (t50 165 +/- 13 min, GEC 2.7 +/-
      0.2) and was similar to that in healthy volunteers (t50 148 +/- 13 min, GEC 3.5
      +/- 0.1). The proportion of patients with slow emptying (GEC < 3.2) was greater
      in non-DM (all = 56%, matched = 60%) than in DM patients (25%) and healthy
      subjects (26%). CONCLUSION: Long-standing type diabetes mellitus is not a risk
      factor for slow GE in critically ill patients.

PMID- 16807710
TI  - Air ionisation in an intensive care unit.

PMID- 16807711
TI  - The effect of birthplace on heat tolerance and mortality in Milan, Italy, 1980
      1989.
AB  - The temperature-mortality relationship follows a well-known J-V shaped pattern
      with mortality excesses recorded at cold and hot temperatures, and minimum at
      some optimal value, referred as Minimum Mortality Temperature (MMT). As the MMT,
      which is used to measure the population heat-tolerance, is higher for people
      living in warmer places, it has been argued that populations will adapt to
      temperature changes. We tested this notion by taking advantage of a huge
      migratory flow that occurred in Italy during the 1950s, when a large number of
      unemployed people moved from the southern to the industrializing north-western
      regions. We have analyzed mortality-temperature relationships in Milan residents,
      split by groups identified by area of birth. In order to obtain estimates of the
      temperature-related risks, log-linear models have been used to fit daily death
      count data as a function of different explanatory variables. Results suggest that
      mortality risks differ by birthplace, regardless of the place of residence,
      namely heat tolerance in adult life could be modulated by outdoor temperature
      experienced early in life. This indicates that no complete adaptation might occur
      with rising external environmental temperatures.

PMID- 16807712
TI  - Neuronal responses in MST reflect the post-saccadic enhancement of short-latency
      ocular following responses.
AB  - Movements of the visual scene evoke short latency ocular following responses
      (OFRs) in monkeys that are mediated at least in part by the medial superior
      temporal area of the cortex (MST). It is known that the sensitivity of the OFR to
      motion is transiently enhanced immediately after a saccade and this post-saccadic
      enhancement is largely secondary to visual reafference during the antecedent
      saccade. As part of an investigation of the neural basis of this post-saccadic
      enhancement, we examined the dependence of OFR-related neuronal activity in MST
      on the post-saccadic delay interval in alert monkeys (Macaca fuscata). Large
      field motion stimuli were applied either 50 or 150 ms after a centering saccade
      and response measures were based on the initial (open-loop) changes in (a) eye
      position and (b) discharge rate. Of the 67% of MST neurons whose OFR-related
      activity showed significant dependence on the post-saccadic delay, 91% mirrored
      the OFR, showing higher sensitivity to motion at the shorter post-saccadic delay
      interval. However, the sensitivity of OFR-related neurons in MST to post-saccadic
      delay varied considerably from cell to cell and, on average, was 79.6% of that
      shown by the OFR. We suggest that this enhanced OFR-related activity in the wake
      of a saccade is causally linked to the visually based post-saccadic enhancement
      of the OFR.

PMID- 16807714
TI  - Aortic rupture: comparison of three imaging modalities.
AB  - We report a case of a 56-year-old man with traumatic aortic rupture (TAR)
      sustained in a motor vehicle accident diagnosed by helical computed tomography,
      aortography, and transesophageal echocardiography. A large majority of patients
      with TAR never make it to the hospital, and for those who do, a timely diagnosis
      is critical for survival. We discuss the merits and pitfalls of the three imaging
      modalities.

PMID- 16807713
TI  - Mitochondrial DNA sequence variation and mutation rate in patients with CADASIL.
AB  - Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL), which is clinically
      characterised by recurrent ischemic strokes, migraine with aura, psychiatric
      symptoms, cognitive decline and dementia. We have previously described a patient
      with CADASIL caused by a R133C mutation in the NOTCH3 gene and with a concomitant
      myopathy caused by a 5650G>A mutation in the MTTA gene in mitochondrial DNA
      (mtDNA). We assume that the co-occurrence of the two mutations is not
      coincidental and that mutations in the NOTCH3 gene may predispose the mtDNA to
      mutations. We therefore examined the nucleotide variation in the mtDNA coding
      region sequences in 20 CADASIL pedigrees with 77 affected patients by
      conformation-sensitive gel electrophoresis and sequencing. The sequence variation
      in mtDNA was then compared with that among 192 healthy Finns. A total of 180
      mtDNA coding region sequence differences were found relative to the revised
      Cambridge reference sequence, including five novel synonymous substitutions, two
      novel nonsynonymous substitutions and one novel tRNA substitution. We found that
      maternal relatives in two pedigrees differed from each other in their mtDNA.
      Furthermore, the average number of pairwise differences in sequences from the 41
      unrelated maternal lineages with CADASIL was higher than that expected among
      haplogroup-matched controls. The numbers of polymorphic sites and polymorphisms
      that were present in only one sequence were also higher among the CADASIL
      sequences than among the control sequences. Our results show that mtDNA sequence
      variation is increased within CADASIL pedigrees. These findings suggest a
      relationship between NOTCH3 and mtDNA.

PMID- 16807715
TI  - Impact of bedside right upper quadrant ultrasonography on radiology imaging.
AB  - Many Emergency Departments (ED) use emergency ultrasonography of the right upper
      quadrant (RUQ) to capture images of the gallbladder in patients with suspected
      gallstones. It is unclear what impact this practice has on additional imaging
      performed by radiology. Patients were enrolled 24 h a day by ED residents and
      attending physicians who have completed an educational program in limited RUQ
      ultrasound. All ultrasounds were videotaped and later reviewed. According to the
      American College of Emergency Physicians' credentialing standards, 25 ultrasounds
      were required before using the results clinically. A total of 352 patients were
      enrolled by 42 physicians over a 1-year period. Two hundred twelve (60.2%) of the
      ultrasounds were performed clinically, with the rest performed for teaching
      purposes. One hundred seventy-nine (50.9%) of the ultrasounds were performed by
      credentialed physicians. One hundred forty-nine (70%) clinical and 29 (20.7%)
      teaching ultrasounds had additional imaging. The average time to follow up
      imaging after discharge from the ED was 8.51 days. Most patients receiving
      emergency ultrasound of their RUQ had follow-up imaging by radiology.

PMID- 16807716
TI  - Controversy concerning E.R. physician performance of procedures.

PMID- 16807717
TI  - Determination of respiratory phase during acquisition of airway cine MR images.
AB  - Subjects were imaged on a 1.5-T Signa MRI system using the head-neck vascular
      coil. An axial fast gradient echo cine, at the base of the second cervical
      vertebra, was obtained. A total of 128 images were acquired with a rapid image
      acquisition (one per second) over several respiratory cycles. The analog signal
      from the MR scanner (RF unblank) was utilized to determine the duration of the
      cine MR sequence. The phase of respiration was determined by analyzing the nasal
      air flow connected via pressure tubing to a pressure transducer outside the MR
      scanner room. We were thus able to determine the phase of respiration during
      acquisition of individual airway cine MR images. There was a wide range of airway
      volume measurements over the respiratory cycle with the lowest volume at end
      expiration and the highest at peak inspiration.

PMID- 16807718
TI  - Intrauterine gastric perforation.
AB  - We describe a case of intrauterine gastric perforation in a 31-week gestational
      age baby girl. The patient presented at birth with abdominal distension,
      respiratory distress, and massive pneumoperitoneum on radiography. The
      perforation was managed by resuscitation, celiotomy, and gastrostomy tube
      placement through the site of perforation. This is the second report of an
      intrauterine gastric perforation in the literature.

PMID- 16807719
TI  - No increase in gastroesophageal reflux after laparoscopic gastrostomy in
      children.
AB  - The objective of the study was to assess the influence of a laparoscopic video
      assisted gastrostomy on acid gastroesophageal reflux (GER). A prospective
      uncontrolled study included 23 neurologically disabled children, from 10 months
      to 15 years of age, all with severe nutritional problems and in need of a
      gastrostomy. They all had a history of clinical GER problems including vomiting,
      choking and chest infections. A 24-h pH monitoring was used for a quantitative
      assessment of GER the day before surgery and 12+/-3 months (7-22 months)
      postoperatively. The gastrostomy was placed on the anterior wall of the stomach
      near the lesser curvature. The main outcome measure was the comparison of the pre
      and postoperative 24-h pH monitoring and the reflux index (RI), i.e. the
      percentage of time with pH below 4. The results showed a non-significant
      reduction of RI from 6.8+/-4.5 preoperatively to 3.7+/-2.0 postoperatively. We
      conclude that a gastrostomy using the video-assisted technique and placing the
      stoma on the anterior wall of the stomach close to the lesser curvature does not
      cause aggravation of acid reflux.

PMID- 16807720
TI  - Mesenchymal hamartoma of the liver: is biopsy always necessary?

PMID- 16807721
TI  - Lock and roll: single-molecule genotyping in situ using padlock probes and
      rolling-circle amplification.
AB  - In this review I will describe the development of a technique that enables
      genotyping of individual DNA molecules in the context of morphologically
      preserved fixed cells, from the fundamental concept published in 1994 to the
      present status. The review describes enzyme-assisted histochemistry approaches to
      achieve highly specific molecular identification reactions coupled to efficient
      signal amplification. The primary molecular identification is accomplished
      through circularization of oligonucleotide probes, called padlock probes. The
      circularization reaction is catalyzed by a DNA ligase, which provides robust
      distinction between single-nucleotide variants under standard reaction
      conditions. To generate a detectable signal from individual circularized probe
      molecules, a DNA polymerase is added that replicates probe circles, generating a
      long tandem-repeated DNA product, easily visualized using a standard epi
      fluorescence microscope. Individual signals are recorded as bright dots,
      providing digital information about the abundance of specific sequences and
      opportunities for simultaneous detection of several targets using spectral
      multiplexing. The importance of strictly target-dependent signal amplification
      will be discussed.

PMID- 16807722
TI  - Treatment of calculi in kidneys with congenital anomalies: an assessment of the
      efficacy of lithotripsy.
AB  - We studied the effectiveness of extracorporeal shock wave lithotripsy (ESWL) in
      the treatment of stones in kidneys with congenital anomalies to determine factors
      that may affect the results. Patients found to have renal calculi in kidneys with
      different types of congenital anomalies were treated using ESWL. All patients
      were investigated by intravenous urography (IVU) to confirm the diagnosis. J
      stents were inserted prior to therapy in renal units with calculi exceeding 1.5
      cm in diameter. Complications encountered and factors affecting success using
      this treatment modality were analysed. Twenty-five patients (18 males, 7 females)
      were studied between August 1988 and July 2005. There were nine patients with
      horseshoe kidneys, eight with ectopic kidneys, three with malrotated kidneys, two
      with duplex renal system, and one patient each with polycystic kidneys and
      hypoplastic kidney. The IVU showed 31 isolated calyceal or renal pelvic stones
      with mean stone burden of 1.44cc. All 25 patients were treated by lithotripsy.
      Twenty-four (77.4%) renal units (in 19 patients) were completely cleared of
      stones, 2 (6.5%) renal units (2 patients) were partially cleared of calculi and
      the procedures failed in 5 (16.1%) renal units (4 patients). Out of five renal
      units in which the procedures failed, open surgery was performed in three renal
      units and percutaneous nephrolithotomy (PCNL) was performed in two. None of the
      25 patients developed any major complications. No significant adverse changes in
      renal function tests were observed at 3-month follow-up. The stone-free rate was
      influenced and reduced by stone size and location in the pelvi-calyceal system.
      Calculi in kidneys with congenital anomalies may be treated successfully by ESWL
      as a first-line therapy in the majority of patients. With position modifications,
      localization of stones may be facilitated and disintegrated. The outcome in
      patients so treated does not differ significantly from that in those with normal
      kidneys.

PMID- 16807723
TI  - Glycinergic transmission.
AB  - Inhibition in the mature central nervous system is mediated by activation of
      gamma-aminobutyric acid (GABA(A)) and glycine receptors. Both receptors belong to
      the same superfamily of ligand-gated ion channels and share common transmembrane
      topology and structural and functional features. Glycine receptors are pentameric
      ligand-gated anion channels composed of two different subunits, named alpha und
      beta, that assemble with a fixed stoichiometric ratio of two alpha to three beta
      subunits. Four genes encoding the alpha subunits exist, whereas only one gene
      encoding the beta subunit has been detected. Ligand binding occurs at the
      interface of alpha and beta subunits. The beta subunit, which is unable to form
      homo-oligomeric receptors, is responsible for assembly and channel properties.
      Moreover, this subunit carries a binding motif for the cytoplasmic protein
      gephyrin, which is believed to mediate synaptic clustering and anchoring at
      inhibitory synapses by interacting with the subsynaptic cytoskeleton. Synaptic
      gephyrin appears to restrict the mobility of glycine receptors diffusing in the
      plane of the plasma membrane, thereby generating dynamic plasma membrane domains
      contributing to the plasticity of inhibitory synapses. Glycine receptors are well
      established as playing important roles in controlling motor functions and sensory
      signaling in vision and audition and those in the dorsal horn of the spinal cord
      are now considered to be new targets for pain therapies. Like GABA(A) receptors,
      glycine receptors have been shown to be depolarizing during development. The
      functional meaning of the developmental switch from excitatory to inhibitory
      glycine receptor action remains to be elucidated.

PMID- 16807724
TI  - Immunohistochemical study of cutaneous nerves in the emu.
AB  - The distribution and chemical content of cutaneous nerves in 3- to 13-day-old emu
      chicks (Dromaius novaehollandiae) were examined by using double-labelling
      immunohistochemistry. Seven different subpopulations of cutaneous nerves were
      identified based on their neurochemistry. No intraepidermal nerve fibres were
      found. However, axons were located within the dermis and were often associated
      with blood vessels, pennamotor muscles and feather follicles or innervated Herbst
      corpuscles. Both similarities and differences exist between subpopulations of
      cutaneous nerves in the emu and volant birds. As in volant birds, a subpopulation
      of cutaneous axons innervates the superficial skin layers and contains
      immunoreactivity to both substance P and calcitonin gene-related peptide (CGRP).
      This suggests that the neuropeptide content of these presumptive free nerve
      endings is conserved throughout the evolution of birds. In contrast, Herbst
      corpuscles in the emu are innervated by axons that contain immunoreactivity for
      CGRP or neuropeptide Y (NPY) but that lack the calbindin D-28k immunoreactivity
      found in fibres innervating Herbst corpuscles of volant birds. Herbst corpuscles
      therefore may have a different chemical content in a flightless species from that
      in volant birds.

PMID- 16807725
TI  - Anesthesiological and intensive care considerations in children undergoing
      extensive cerebral excision procedure for congenital epileptogenic lesions.
AB  - INTRODUCTION: Epilepsy is a relatively common condition in childhood with a
      generally favorable prognosis of the affected population. Nevertheless, a
      significant minority of the treated children do not respond to the medical
      treatment so that surgical treatment is necessary. While minor surgical
      procedures have a negligible incidence of mortality, major ones may carry a
      significant risk of perioperative complications. The leading cause of mortality
      is represented by hemorrhagic derangements after high intraoperative and
      postoperative blood loss, mostly in very young patients. Therefore, restoration
      of euvolemia, detection and correction of related bleeding disorders represent
      the major concern for pediatric neuroanesthesiologists and intensivists
      throughout the perioperative period. The present report is focused on the
      anesthesia and intensive care management of the surgical epileptic patient.
      CONCLUSION: Authors recommend that these high-risk procedures should be performed
      in highly experienced centers where pediatric neurosurgery is performed daily.

PMID- 16807727
TI  - Epilepsy related to hypothalamic hamartomas: surgical management with special
      reference to gamma knife surgery.
AB  - OBJECTIVE: A large spectrum of surgical techniques can be proposed to young
      patients presenting with hypothalamic hamartomas (HH) associated with severe
      epilepsy. The aim of this report is to point on some clinical and anatomical
      parameters supposed to influence the choice of the surgical approach and to
      emphasize the specific role of radiosurgery. MATERIALS AND METHODS: We reviewed
      both our experience and the recent literature based on a Pubmed search. Lateral
      pterional, midline frontal through the lamina terminalis, transcallosal
      interforniceal approaches, endoscopic treatment through the foramen of Monro,
      disconnecting surgery, radiofrequency ablation, brachytherapy and gamma knife
      surgery (GKS) were all considered. Mortality, morbidity, and efficacy of each of
      these techniques were compared. Specific limits, difficulties, and constraints
      were taken into account. Our experience of radiosurgery is based on a prospective
      trial which enrolled 60 patients with HH and associated severe epilepsy between
      October 1999 and December 2005. RESULTS: Several surgical techniques can lead to
      a real reversal of the epileptic encephalopathy. The main factors for the
      decision-making process are the age, the size of the lesion and its anatomical
      type (according to our original classification), the severity of the epilepsy,
      and the severity of the cognitive/psychiatric comorbidity. In our prospective
      trial (GKS), 27 patients have a follow-up superior to 3 years. Among those, 59.2%
      have an excellent result with a dramatic behavioral and cognitive improvement and
      are completely seizure-free (37%) or have only rare non-disabling seizures
      (22.2%). No permanent neurological complication has been observed so far; three
      patients have presented a transient poikilothermia. GKS is clearly the safer
      approach for these difficult patients. Young patients with severe epilepsy and
      comorbidity must be operated on using a curative approach as early as possible.
      Very large type VI or mixed type with a large component above the floor of the
      third ventricle must be disconnected and then the upper remnant can be ideally
      treated by GKS (staged surgery). Type V (rarely epileptic) and IV are frequently
      operable by disconnection. Type I HH deeply embedded in the hypothalamus are
      operated on by GKS efficiently and safely. Type II HH can be operated on either
      endoscopically or transcallosally or by GKS depending on the parents' choice and
      severity of epilepsy. In small type III HH, GKS is a safer procedure, due to the
      very close relationship to the fornix and mammillary bodies. In very large type
      III HH, transcallosal interforniceal approach is proposed but with significant
      risks especially concerning short-term memory. When the lesion is sufficiently
      small, GKS is globally offering the patient a rate of seizure cessation
      comparable to microsurgery with, however, a much lower risk (no neurological
      deficit reported till now). CONCLUSION: Our first results indicate that GKS is as
      effective as microsurgical resection and very much safer. GKS also allows
      avoiding the vascular risk related to radiofrequency lesioning or stimulation.
      The disadvantage of radiosurgery is its delayed action. Longer follow-up is
      mandatory for a reliable evaluation of the role of GKS. The early effect on
      subclinical discharges turns out to play a major role in the dramatic improvement
      of sleep quality, behavior, and developmental learning acceleration at school.

PMID- 16807726
TI  - Intracranial aneurysms in children under 1 year of age: a systematic review of
      the literature.
AB  - OBJECTIVE: Intracranial aneurysms are very rare in early childhood. Because the
      location, morphology as well as the clinical and radiological presentation of
      these aneurysms seem to be different from those in adults, we performed a
      systematic review of the literature to discuss the clinical, morphological, and
      radiological features of intracranial aneurysms in the first year of life.
      MATERIALS AND METHODS: A computerized search of both Pubmed and EMBASE from
      before 1966 to 2005 was performed. Included were all articles that dealt with
      cases in which an intracranial aneurysm was demonstrated in children under 1 year
      of age. RESULTS: We found 110 articles in which 131 cases of an intracranial
      aneurysm in children under 1 year were presented. The mean age at diagnosis of
      the aneurysm was 4.9+/-3.5 months with a male to female ratio of 1.1. There was a
      hemorrhagic presentation in 73% (n=96). The patients presenting with a hemorrhage
      were younger (mean 4.3 vs 6.7 months, P<0.001) and tended to have smaller-sized
      (i.e.<2.5 cm) aneurysms (P=0.07). The aneurysm was defined as traumatic or
      infectious in 15 and 13 cases, respectively. In 21% (n=27), there was various
      vascular or congenital co-morbidity. In 76%, the aneurysm was located in the
      anterior circulation. The prevalence of aneurysms on the middle cerebral artery
      (MCA) was nearly three times higher than on any other vessel. The mean aneurysm
      size was 1.8+/-1.4 cm, with 30 giant aneurysms (>2.5 cm). The giant aneurysms
      were significantly more often located in the posterior circulation (43 vs 16%,
      P=0.01). The mean period of follow-up was 13.6+/-24.8 months. The Glasgow Outcome
      Scale (GOS) could be derived in 106 cases: 50% had an excellent outcome (GOS of
      5). CONCLUSIONS: The presentation of arterial aneurysms in children under the age
      of 1 year differs from that in adults with a significantly higher prevalence of
      giant aneurysms in the posterior circulation. The prevalence of aneurysms on the
      MCA is nearly three times higher than on any other vessel. The patients
      presenting with a hemorrhage were younger and tended to have smaller-sized
      aneurysms. Our study did not confirm the male predominance that has thus far been
      associated with pediatric aneurysms. The outcome is comparable or slightly better
      than in adults.

PMID- 16807728
TI  - Endoscopic endonasal approaches to anterior skull base defects in pediatric
      patients.
AB  - INTRODUCTION: We studied 12 pediatric patients with congenital or acquired
      anterior skull base defects. All subjects underwent surgery owing to progressive
      symptoms. The endoscopic endonasal approach is a new method in the treatment of
      this pathology in children. MATERIALS AND METHODS: Twelve children had surgery to
      correct anterior skull base defects: seven patients with a spontaneous anterior
      basal meningoencephalocele and five with posttraumatic cerebrospinal fluid (CSF)
      leakage. The defects were repaired using the endoscopic endonasal approach, which
      combined with the fluorescein diagnostic test, detects the exact location of the
      skull base defect. Different closure techniques were used to obtain a permanent
      graft, depending on the type, location, and size of the defect. An intraoperative
      fluorescein test confirmed the absence of CSF leakage after surgery. RESULTS: The
      follow-up period ranged from 3 to 72 months. Symptoms resolved in all patients
      after surgery and none of them experienced complications or recurrence of CSF
      leakage. Postoperative magnetic resonance scans showed that the defect had
      successfully been repaired in all patients. DISCUSSION: The surgical treatment of
      skull base defects in children reduces life-threatening risks, which include
      infections, CSF leaks, and enlargement or trauma of the sac. The endoscopic
      technique minimizes surgical scars and has little impact on brain tissue. The
      endoscopic endonasal approach to the anterior skull base helps to preserve the
      physiology of the nose and sinuses and reduces the impact on the still developing
      splanchnocranium in pediatric patients. It ensures a definitive repair of the
      defect and requires a very short inpatient period.

PMID- 16807729
TI  - Population clinical pharmacology of children: modelling covariate effects.
AB  - INTRODUCTION: Population modelling using mixed effects models provides a means to
      study variability in paediatric drug responses among individuals representative
      of those in whom the drug will be used clinically. DISCUSSIONS: Explanatory
      covariates explain the predictable part of the between-individual variability.
      Growth and development are two major aspects of children not seen in adults.
      These aspects can be investigated by using size and age as covariates. Problems
      attributable to co-linearity can be approached by using size as the first
      covariate. Size standardisation is achieved using allometric scaling, a
      mechanistic approach that has a strong theoretical and empirical basis. Age is
      used to describe the maturation of clearance. The quantitative models (linear,
      exponential, first-order, variable slope sigmoidal) used to describe this
      maturation process vary depending on the span of the ages under investigation.
      Measures of response are not always straightforward and can be more difficult to
      quantify in children. CONCLUSION: Covariate investigation in children is
      improving the understanding of developmental aspects of drug disposition and
      effects in the paediatric population, ultimately leading to more effective use of
      medications.

PMID- 16807730
TI  - Population clinical pharmacology of children: general principles.
AB  - INTRODUCTION: Population modelling using mixed-effects models provides a means to
      study variability in drug responses among individuals representative of those for
      whom the drug will be used clinically. DISCUSSION: The advantages of these models
      in paediatric studies are that they can be used to analyse sparse data, sampling
      times are not crucial and can be fitted around clinical procedures and
      individuals with missing data may still be included in the analysis. The
      introduction of explanatory covariates explains the predictable part of the
      between-individual variability. Simulations using parameter estimates and their
      variability can be used to investigate large numbers of children--many more than
      is possible in studies dealing with real children--for a fraction of the cost,
      which is an advantage when developing clinical trials. Paediatric population
      modelling has expanded greatly in the past decade and is now a routine procedure
      during the development and investigation of drugs. Children have benefitted and
      will continue to benefit from this approach.

PMID- 16807731
TI  - Intraoperative versus postoperative electrochemotherapy in high grade soft tissue
      sarcomas: a preliminary study in a spontaneous feline model.
AB  - Feline soft tissue sarcomas are spontaneous, rapidly growing, and aggressive
      neoplasms that mimic their human counterpart. The purpose of this study was to
      evaluate the feasibility and efficacy of electrochemotherapy (ECT) in an adjuvant
      fashion for the treatment of feline sarcomas, and the possibility of repeated
      treatments in the case of recurrence. Cats with fibrosarcoma (FSA) were assigned
      to receive surgery or surgery plus ECT. Feline patients recruited in the ECT
      study were enrolled in a microscopic arm (39 patients) or a macroscopic arm (19
      patients) on the basis of their tumor status (absence or presence of gross
      disease). Patients received local injection of bleomycin followed by bursts of
      eight biphasic pulses at a voltage of 1,300 V/cm for postoperative and of 800
      V/cm for intraoperative treatments. The median time to recurrence was 4 months
      for cats treated with surgery alone, 19 months for the postoperative cohort, and
      12 months for the intraoperative group. Moreover, ten patients with recurring
      neoplasms were retreated and experienced responses lasting 6 to 28+ months. Side
      effects were minimal. Of interest, the metastatic rate (1.7%) in our patients was
      negligible: only one cat had distant spread. The results suggest that ECT is a
      well tolerated and potentially useful addition to surgery in controlling high
      grade sarcomas. On the basis of these results, additional evaluations are
      warranted in pets and in humans.

PMID- 16807732
TI  - Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in
      advanced pancreatic adenocarcinoma.
AB  - BACKGROUND: PEFG regimen (cisplatin and epirubicin 40 mg/m2 day 1, gemcitabine
      600 mg/m2 days 1 and 8, 5-fluorouracil (FU) 200 mg/m2/day continuous infusion)
      significantly improved the outcome of patients with advanced pancreatic
      adenocarcinoma (PA) with respect to standard gemcitabine in a previous phase III
      trial. This regimen was subsequently modified in a dose-finding study by
      increasing dose intensity of cisplatin and epirubicin (both at 30 mg/m2 every 14
      days) and of gemcitabine (at 800 mg/m2 every 14 days). Results of a consecutive
      series treated by dose-intense PEFG regimen are herewith reported. MATERIAL AND
      METHODS: Dose-intense PEFG was administered to chemotherapy-naive patients with
      stages III-IV PA, < 75 years, performance status (PS) > 50, till progressive
      disease or for a maximum of 6 months. RESULTS: Between January 2004 and June
      2005, 49 (31 or 63% metastatic) patients, median age 62 years, median PS 80, were
      treated with dose-intense PEFG. Partial response and stable disease was observed
      in 24 (49%) and 16 (33%) patients, respectively; 31 patients were progression
      free at 6 months (PFS-6 = 63%). Median survival was 10.5 months and 1-year
      overall survival (OS) was 48% (95% confidence interval: 33-61%). Main grade 3-4
      toxicity was: neutropenia in 26% of patients, stomatitis and fatigue in 8%,
      anaemia, diarrhoea, nausea/vomit in 6%, febrile neutropenia and thrombocytopaenia
      in 4%, hand-foot syndrome in 2%. CONCLUSION: When compared with 84 patients
      treated by classical PEFG at the same institution, dose-intense PEFG was not
      inferior in terms of PFS-6 (63 versus 57%), 1-year OS (48 versus 42%) and
      response rate (49 versus 49%); it allowed to increase dose intensity for
      gemcitabine by 32%, for cisplatin and epirubicin by 36% (FU reduced by 3%), to
      significantly reduce grade 3-4 hematological toxicity (neutropenia: 26 versus
      86%; P < 0.00001; thrombocytopaenia: 4 versus 58%; P < 0.00001) and to reduce by
      one-third the number of outpatient accesses. The new PEFG schedule appears more
      suitable for clinical use and should be preferred as a basis for further
      development of therapeutic strategies against pancreatic cancer.

PMID- 16807734
TI  - [Neurodermatitis].

PMID- 16807733
TI  - Genetic characterization of the polycotyledon locus in tomato.
AB  - Developmental mutants serve as a useful material to unravel the mechanisms
      necessary for organ development. The polycotyledon (poc) mutant of tomato, with
      multiple cotyledons in the seedling and varied phenotypic effects in the adult
      plant is one such mutant. Studies using physiological and anatomical methods in
      our lab suggest that POC is involved in the negative regulation of polar auxin
      transport, which is likely the reason for the pleiotropic phenotype in the
      mutant. Because of the physiological significance of the polycotyledon mutant
      described in this paper and also being first of its kind in tomato and also other
      plant species, we are using a map-based cloning approach to map the polycotyledon
      gene. Molecular mapping of this locus using segregating interspecific F2 mapping
      population localized polycotyledon gene close to TG424 marker on the long arm of
      chromosome 9. The closest marker mapped was a PCR marker identified in this
      study, E8A2 at a distance of 7.4 cM from the poc locus. The absence of tightly
      linked RAPD markers and the non-availability of more mapped markers in this
      region led us to initiate chromosome walk to polycotyledon gene. Both the
      flanking markers TG248 and E8A2 were used to screen the BAC library and a contig
      was developed for TG248 marker. The BAC-end sequences were analyzed for their use
      as RFLP markers to enrich this region for markers. Analysis of the BAC-end
      sequences revealed that poc is localized in the region surrounded by copia-like
      retrotransposon elements explaining the absence of markers in the euchromatin
      region on long arm of chromosome 9. Further studies identified two BAC-end
      sequences which mapped around the poc locus and also indicated very low physical
      versus genetic distance ratio in this region. The double mutant analyses of poc
      with the other two known polycotyledon mutants of tomato, pct and dem revealed
      allelism with pct; therefore, the poc mutant was named as pct1-2, and also the
      original pct mutant was renamed as pct1-1.

PMID- 16807735
TI  - [Cartilage repair in the knee joint].
AB  - Full thickness defects of the articular cartilage in the knee joint have lower
      regenerative properties compared to chondral lesions of the ankle. In order to
      avoid early osteoarthritis, symptomatic articular cartilage defects in younger
      patients should undergo biological reconstruction as early as possible. There are
      different surgical procedures available to achieve a biological resurfacing of
      the articular joint line. Numerous animal experiments and clinical studies have
      shown that early biological reconstruction of circumscribed cartilage defects in
      the knee is superior to a conservative or delayed operative treatment. This
      effect refers not only to the defect healing but also to the elimination of
      changes following secondary osteoarthritis. The different surgical procedures can
      be differentiated concerning the various indications and the final outcome.
      Additional malalignment, meniscus tears, and/or ligament instabilities should be
      treated simultaneously together with the cartilage resurfacing. The mid- and long
      term results of the different current techniques are promising, but further
      modifications and improvements are needed.

PMID- 16807736
TI  - [Diagnosis and treatment of the Essex-Lopresti lesion. Literature review and four
      case reports].
AB  - BACKGROUND: A fracture of the radial head in combination with a rupture of the
      interosseous membrane and lesion of the distal radioulnar joint known as Essex
      Lopresti lesion is a rare injury. Usually it is caused by a high-energy trauma.
      Initially unrecognized distal radioulnar dislocations often show poor results.
      MATERIAL AND METHOD: Four case reports are presented to discuss the trauma
      mechanism together with diagnostic and treatment options. Especially the accuracy
      of ultrasound to diagnose an interosseous membrane disruption was evaluated.
      RESULTS: After an average of 35 months all patients were examined using the
      Morrey score and the modified score of Green and O'Brien. Initially the extent of
      the injury was not diagnosed in three cases. According to the score values the
      average results have been fair. CONCLUSIONS: An early diagnosis is the key for
      the correct treatment of an Essex-Lopresti lesion based on the classification of
      Edwards and Jupiter. In addition to the clinical and radiological assessment
      ultrasound should be used to diminish the rate of unrecognized interosseous
      membrane disruptions.

PMID- 16807737
TI  - [Treatment of the combined pelvic and thoracic trauma in the emergency room].
AB  - Priorities in the diagnosis and treatment of a multiple trauma with injuries to
      the thorax and pelvis are usually determined by the pattern and the severity of
      the injury sustained. In this case a haemodynamically unstable patient with
      severest pelvic trauma and a moderate thoracic trauma developed progressive
      haemodynamic instability during an intervention to the pelvis, resulting in a
      lethal outcome for the patient. The cause only became obvious when computed
      tomography of the thorax (CTT) was performed which was able to demonstrate venous
      pulmonary bleeding compressing the left atrium. In haemodynamically unstable
      patients with a major pelvic trauma combined with a moderate thoracic trauma,
      early CTT should therefore be a main priority in the initial management of such
      patients in the resuscitation room. The time spent on such a diagnostic procedure
      seems to be worth the information gained, which can significantly influence the
      initial choices and priorities in treatment.

PMID- 16807738
TI  - [Simultaneous rupture of a patellar tendon and contralateral quadriceps tendon].
AB  - The simultaneous bilateral rupture of the quadriceps tendon is a rare injury;
      only occasional reports exist about the bilateral simultaneous rupture of the
      patellar tendon. Degenerative changes of the tendon due to drugs or diseases lead
      to the rupture. We describe two cases of simultaneous rupture of the patellar and
      contralateral quadriceps tendons; only one patient had special risks. We report
      the management of therapy and the functional results using the Lysholm score and
      Knee Rating Scale.

PMID- 16807739
TI  - [Misinterpretation of anterior pelvic ring fractures in the elderly].
AB  - Clinical outcome following pelvic ring fractures of AO/OTA type-A in the elderly
      is often unsatisfying because the posterior pelvic ring fracture is
      underdiagnosed and patients with type B fractures were conservatively treated
      like patients with type A fractures. This so-called "A-B" problem was
      systematically analyzed in our patients with pelvic ring fractures. 183 patients
      were treated with pelvic ring fractures. Primarily, the injuries were classified
      as follows: 81 type A, 38 type B, and 64 type C. The diagnosis was changed from
      type A to type B injury in seven patients. Parameters of investigation included
      fracture type, duration of symptoms, treatment, and outcome score according to
      the German Multicenter Study Group Pelvis. Persistent pain in the sacral area
      over an average of 2 (1-6) weeks was found in all patients. The CT scan revealed
      in all patients a transalar sacral impression fracture in the sense of an
      internal rotationally unstable injury of type AO/OTA B 2.1. The treatment
      consisted in a supra-acetabular external fixator for an average of 3 weeks. After
      4 weeks the mean pelvis outcome score was 9 (7-10) points. In cases of persistent
      pain for more than 2 weeks after transpubic pelvic ring fractures in the elderly
      further investigation by CT scan should be recommended to exclude a concomitant
      sacral fracture, which then could be safely treated by a supra-acetabular
      external fixator.

PMID- 16807740
TI  - [Persistent mydriasis after deep lamellar keratoplasty].

PMID- 16807741
TI  - [Current pathophysiological aspects of systemic sclerosis].
AB  - Systemic scleroderma is characterized by a chronic inflammatory process of
      unknown etiology resulting in an increased deposition of connective tissue
      proteins in the involved organs. Involvement of the vascular system and the
      resulting fibrosis lead to atrophy and malfunction of the involved internal
      organs and the skin. Due to the development of new therapeutic concepts in
      particular with regard to the vascular involvement, the interaction between the
      vascular system and the connective tissue moves increasingly into focus. This
      review describes the major advancemades during recent years for the understanding
      of the pathophysiology of systemic scleroderma.

PMID- 16807742
TI  - [Expression und function of the ORL-1 receptor on human leukocytes].
AB  - BACKGROUND: The ORL-1 receptor is expressed by human leukocytes. Limited
      knowledge exists about the function and interaction between the nervous and
      immune systems. The aim of our study was to investigate the expression of the
      nociceptin-ORL-1 receptor system on different leukocyte subsets and the influence
      of the ORL-1 receptor on the intracellular production of cytokines. METHODS:
      Blood from healthy volunteers of different age and sex was analysed for the
      expression of the ORL-1 receptor by PCR and flow cytometry and the influence of
      nociceptin on the LPS-induced production of intracellular cytokines by flow
      cytometry. RESULTS: The ORL-1 receptor mRNA is expressed by granulocytes,
      lymphocytes and monocytes. We could also show the expression of the ORL-1
      receptor protein on the cell surface of all types of white blood cells.
      Nociceptin has no influence on LPS-induced cytokine production in human
      monocytes. There was neither a difference between young and old nor between male
      or female volunteers. CONCLUSION: The ORL-1 receptor is expressed by all subtypes
      of leukocytes. The function of this receptor is not the modulation of cytokine
      production and requires further studies.

PMID- 16807743
TI  - Does endoluminal coil embolization cause distension of intracranial aneurysms?
AB  - INTRODUCTION: The aim of the present study was to determine whether intracranial
      aneurysms are distended after coil embolization and to evaluate the
      distensibility of ruptured aneurysms treated with endovascular coiling. METHODS:
      This was a prospective study of 20 consecutive patients with 22 aneurysms, who
      presented with a ruptured cerebral aneurysm and were treated with endovascular
      coiling of the aneurysm in a single institution. A diagnostic digital subtraction
      angiography (DSA) and a three-dimensional radiographic angiography (3DRA) were
      performed with bi-plane angiography equipment (Philips V5000) immediately before
      and after the embolization procedure to detect volume enlargement of the aneurysm
      after embolization, and the extent of the enlargement. A simulation study with
      steel spheres was carried out to study the possible error of over-estimation of
      the postembolization volume due to the beam-hardening artifact. RESULTS: There
      was no procedure-related rupture of the aneurysms. The percentage by volume of
      solid coil within the coil mass ranged from 15.78% to 82.01% in the present
      series. All aneurysms showed distension which ranged from 0.09% to 34.23%. The
      distensibility of the aneurysms was 34.23%. Error due to the beam-hardening
      artifact was negligible. CONCLUSION: Endoluminal packing of intracranial saccular
      aneurysms with embolization coils could cause a certain degree of distension in
      aneurysms treated with coil embolization, with the degree of distension up to
      34.2%. Intracranial aneurysms were able to tolerate a certain degree of
      endoluminal distension without a risk of immediate rupture, even those that had
      ruptured recently.

PMID- 16807744
TI  - Generation and maintenance of diversity in the cattle MHC class I region.
AB  - Major histocompatibility complex (MHC) class I genes play a crucial role in the
      immune defence against intracellular pathogens. An important evolutionary
      strategy is to generate and maintain a high level of diversity in these genes.
      Humans express three highly polymorphic classical MHC class I genes (HLA-A, HLA-B
      and HLA-C). In contrast, some species, for example rat and rhesus macaque,
      maintain diversity by generation of haplotypes that vary considerably with regard
      to the number and combination of transcribed genes. Cattle appear to use both
      strategies. We show that various combinations of six apparently classical genes,
      three of which are highly polymorphic, are transcribed on different haplotypes.
      Although additional sequences were identified in both cDNA and gDNA, it was not
      possible to assign them to any of these defined genes. Most were highly divergent
      or were non-classical class I genes. Thus, we found little evidence for frequent
      duplication and deletion of classical class I genes as reported in some other
      species. However, the maintenance of class I diversity in cattle may involve
      limited gene shuffling and deletion, possibly as a result of unequal crossing
      over within the class I region.

PMID- 16807745
TI  - Expansion of the mast cell chymase locus over the past 200 million years of
      mammalian evolution.
AB  - The acidic granules of natural killer (NK) cells, T cells, mast cells, and
      neutrophils store large amounts of serine proteases. Functionally, these
      proteases are involved, e.g., in the induction of apoptosis, the recruitment of
      inflammatory cells, and the remodeling of extra-cellular matrix. Among the
      granule proteases are the phylogenetically related mast cell chymases, neutrophil
      cathepsin G, and T-cell granzymes (Gzm B to H and Gzm N), which share the
      characteristic absence of a Cys(191)-Cys(220) bridge. The genes of these
      proteases are clustered in one locus, the mast cell chymase locus, in all
      previously investigated mammals. In this paper, we present a detailed analysis of
      the chymase locus in cattle (Bos taurus) and opossum (Monodelphis domestica). The
      gained information delineates the evolution of the chymase locus over more than
      200 million years. Surprisingly, the cattle chymase locus contains two alpha
      chymase and two cathepsin G genes where all other studied chymase loci have
      single genes. Moreover, the cattle locus holds at least four genes for
      duodenases, which are not found in other chymase loci. Interestingly, duodenases
      seem to have digestive rather than immune functions. In opossum, on the other
      hand, only two chymase locus-related genes have been identified. These two genes
      are not arranged in one locus, but appear to have been separated by a marsupial
      specific chromosomal rearrangement. Phylogenetic analyses place one of the
      opossum genes firmly with mast cell alpha-chymases, which indicates that the
      alpha-chymase had already evolved as a separate, clearly identifiable gene before
      the separation of marsupials and placental mammals. In contrast, the second gene
      in opossum is positioned phylogenetically between granzymes, cathepsin G, and the
      duodenases. These genes, therefore, probably evolved as separate subfamilies
      after the separation of placental mammals from marsupials. In platypus, only one
      chymase locus-like sequence could be identified. This previously published
      "granzyme" does not cluster clearly with any of the chymase locus gene families,
      but shares the absence of the Cys(191)-Cys(220) bridge with the other chymase
      locus proteases. These findings indicate that all chymase locus genes are derived
      from a single ancestor that was present more than 200 million years ago.

PMID- 16807746
TI  - Rapid lineage-specific diversification of the mast cell chymase locus during
      mammalian evolution.
AB  - Serine proteases constitute the major protein granule content of cells of several
      hematopoietic cell lineages. A subgroup of these proteases, including the mast
      cell chymases, neutrophil cathepsin G, and T cell granzymes B to F and N, are in
      all investigated mammals encoded in one locus, the chymase locus. It is
      interesting to note that this locus has diversified greatly during the last 95
      Myr of mammalian evolution. This divergence is exemplified by the presence of
      Mcpt8-related genes and multiple beta-chymases in the mouse and rat, which lack
      direct counterparts in primates and in seven functional granzyme genes in the
      mouse where the human locus has only two. To study the expansion of the locus
      during rodent evolution and to better understand the evolutionary origin of beta
      chymases and the Mcpt8-family, we have performed a detailed analysis of the
      chymase locus of four mammalian species, i.e., human, dog, mouse, and rat. As a
      result, we report here a second chymase-like gene in dog, Cma2, which clusters
      with beta-chymases in phylogenetic analyses. This finding supports a duplication
      of the common ancestor for alpha- and beta-chymases before the major radiation of
      placental mammals, and a loss of the ancestral beta-chymase gene sometime during
      primate evolution. Moreover, we show that in the rat, the Mcpt8-family
      diversified relatively recently together with sequences related to the beta
      chymase Mcpt2. Eight novel genes were identified in the duplication region, four
      of which are predicted to be functional. Duplications of rat granzyme B- and C
      like sequences occurred seemingly independently within a similar time frame, but
      did not give rise to functional genes. Due to the duplications in rat and
      deletions in the carnivore/primate lineage, the rat chymase locus is
      approximately 15 and 9 times larger than its counterparts in dog and human,
      respectively. These findings illustrate the importance of gene duplications in
      conferring rapid changes in mammalian genomes.

PMID- 16807747
TI  - Causes of incidental neutropenia in adulthood.
AB  - The incidental discovery of neutropenia during routine blood counting represents
      a common problem for clinicians. However, there are no reported data of
      systematic evaluations of adults with incidental neutropenia. As such, this was
      the aim of the present study. Ninety-seven adults with incidental neutropenia
      were submitted to a clinical and laboratory approach including medical
      evaluation, complete blood count (CBC), serial CBC, direct and indirect
      antiglobulin test, bone marrow smear and biopsy, assessment of folate, vitamin
      B12 and iron status, serum liver enzymes, serum proteins, serological exams for
      hepatitis B and C virus, cytomegalovirus, mononucleosis, human immunodeficiency
      virus and toxoplasmosis, detection of lupus erythematosus cells, antinuclear and
      anti-DNA antibodies and rheumatoid factor, dosage of free thyroxin and
      thyrotropin, chest roentgenogram and abdominal echography. Chronic idiopathic
      neutropenia of adults was identified in 34.0% of the individuals, neutropenia due
      to exposure to chemical agents was seen in 16.5%, infectious diseases in 9.3%,
      autoimmune diseases in 9.3%, haematological diseases in 9.3%, thyroid disorders
      in 8.2%, ethnic neutropenia in 7.2%, drug-related neutropenia in 2.1%, cyclic
      neutropenia in 2.1% and iron deficiency in 2.1%. Recovery or improvement of the
      neutrophil count was seen upon treatment or recuperation from infectious,
      autoimmune, haematological and thyroid diseases and iron supplementation. We
      conclude that the evaluation of individuals with incidental neutropenia using a
      structured approach may make the identification of clinically silent diseases
      possible, and provide an opportunity for early treatment, avoiding complications
      of the diseases and consequences of neutropenia.

PMID- 16807748
TI  - Dramatic improvement in hereditary hemorrhagic telangiectasia after treatment
      with the vascular endothelial growth factor (VEGF) antagonist bevacizumab.

PMID- 16807749
TI  - Diffusion, cross-diffusion and competitive interaction.
AB  - The cross-diffusion competition systems were introduced by Shigesada et al. [J.
      Theor. Biol. 79, 83-99 (1979)] to describe the population pressure by other
      species. In this paper, introducing the densities of the active individuals and
      the less active ones, we show that the cross-diffusion competition system can be
      approximated by the reaction-diffusion system which only includes the linear
      diffusion. The linearized stability around the constant equilibrium solution is
      also studied, which implies that the cross-diffusion induced instability can be
      regarded as Turing's instability of the corresponding reaction-diffusion system.

PMID- 16807750
TI  - Transgenic Acacia sinuata from Agrobacterium tumefaciens-mediated transformation
      of hypocotyls.
AB  - Transgenic herbicide tolerant Acacia sinuata plants were produced by
      transformation with the bar gene conferring phosphinothricin resistance.
      Precultured hypocotyl explants were infected with Agrobacterium tumefaciens
      strain EHA105 in the presence of 100 microM acetosyringone and shoots regenerated
      on MS (Murashige and Skoog, 1962, Physiol Plant 15:473-497) medium with 13.3
      microM benzylaminopurine, 2.6 microM indole-3-acetic acid, 1 g l(-1) activated
      charcoal, 1.5 mg l(-1) phosphinothricin, and 300 mg l(-1) cefotaxime.
      Phosphinothricin at 1.5 mg l(-1) was used for the selection. Shoots surviving
      selection on medium with phosphinothricin expressed GUS. Following Southern
      hybridization, eight independent shoots regenerated of 500 cocultivated explants
      were demonstrated to be transgenic, which represented transformation frequency of
      1.6%. The transgenics carried one to four copies of the transgene. Transgenic
      shoots were propagated as microcuttings in MS medium with 6.6 microM 6
      benzylaminopurine and 1.5 mg l(-1) phosphinothricin. Shoots elongated and rooted
      in MS medium with gibberellic acid and indole-3-butyric acid, respectively both
      supplemented with 1.5 mg l(-1) phosphinothricin. Micropropagation of transgenic
      plants by microcuttings proved to be a simple means to bulk up the material.
      Several transgenic plants were found to be resistant to leaf painting with the
      herbicide Basta.

PMID- 16807751
TI  - Copper-induced changes in the growth, oxidative metabolism, and saponin
      production in suspension culture roots of Panax ginseng in bioreactors.
AB  - Roots of Panax ginseng exposed to various concentrations of Cu (0.0, 5, 10.0,
      25.0, and 50.0 microM) accumulated high amounts of Cu in a concentration
      dependent and duration-dependent manner. Roots treated with 50 microM Cu resulted
      in 52% and 89% growth inhibition after 20 and 40 days, respectively. Saponin
      synthesis was stimulated at a Cu concentration between 5 and 25 muM but decreased
      at 50 microM Cu. Malondialdehyde content (MDA), lipoxygenase activity (LOX),
      superoxide ion (O2*-) accumulation, and H2O2 content at 5 and 10 microM Cu
      treated roots were not increased but strongly increased at 50 microM Cu resulting
      in the oxidation of ascorbate (ASC) and glutathione (GSH) to dehydroascorbate
      (DHA) and glutathione disulfide (GSSG), respectively indicating a clear oxidative
      stress. Seven well-resolved bands of superoxide dismutase (SOD) were detected in
      the gel and an increase in SOD activity seemed to be mainly due to the induction
      of Fe-SOD 3. Five to 10 microM Cu slightly induced activity of ascorbate
      peroxidase (APX) and dehydroascorbate reductase (DHAR), guaiacol peroxidase (G
      POD) but inhibited monodehydroascorbate reductase (MDHAR) and glutathione
      reductase (GR) enzyme activities. No changes in catalase (CAT) activity and in
      activity gel were found up to 25 microM Cu, but both G-POD and CAT activities
      were inhibited at 50 microM Cu. Glutathione metabolism enzymes such as gamma
      glutamylcysteine synthetase (gamma-GCS), glutathione-S-transferase (GST), and
      glutathione peroxidase activities (GPx) were activated at 5 and 10 microM Cu but
      were strongly inhibited at 50 microM Cu due to the Cu accumulation in root
      tissues. The strong depletion of GSH at 50 microM Cu was associated to the strong
      induction of gamma-glutamyltranspeptidase (gamma-GGT) activity. These results
      indicate that plant could grow under Cu stress (5-25 microM) by modulating the
      antioxidant defense mechanism for combating Cu induced oxidative stress.

PMID- 16807752
TI  - Correlation of intercondylar notch cross sections to the ACL size: a high
      resolution MR tomographic in vivo analysis.
AB  - INTRODUCTION: To correlate cross sections of the intercondylar notch to cross
      sections of the anterior cruciate ligament (ACL) and to analyze gender-related
      differences in notch and ACL morphometry with an attempt to explain the
      observation that a small intercondylar notch and the female gender predispose to
      a rupture of the ACL. MATERIAL AND METHODS: High resolution MR imaging was
      performed on a 1.5 T magnet using a dedicated extremity-coil in ten left and ten
      right knee joints of 20 volunteers (10 male, 10 female, mean age 25 years) with
      no history of knee abnormalities. Continuous axial T2-weighted MR images
      perpendicular to the longitudinal axis of the ACL were acquired. Cross-sectional
      areas of the ACL midsubstance at the contact area to the posterior cruciate
      ligament were measured. For imaging and evaluation of the osseous limits of the
      intercondylar notch a 3D-dataset of the knee was acquired. Anterior, middle and
      posterior planes of the intercondylar notch were calculated and analyzed for
      measurement of the notch area AN and notch width index NWI. The ratio of the ACL
      cross-sectional area of the ACL and the cross-sectional area of the notch was
      defined as the ACL notch index (ANI) and used as a standardized tool for
      evaluation. For statistical evaluation, linear regression analysis was performed.
      Mean values between male and female were compared using a t test. In addition,
      five matched pairs of male and female volunteers of same height were analyzed.
      RESULTS: Mean cross-sectional size of the ACL at the crossing with the PCL was
      54.4 +/- 20.4 mm2. Regression analysis showed a significant correlation (P <
      0.05) of the ACL cross-sectional area to the notch areas on all three planes and
      NWI, respectively. Comparison between the sexes revealed that female participants
      had significantly smaller cross-sectional areas of the ACL, the notch areas, the
      NWI and ANI. This difference was found for both the complete study group and the
      matched pairs of same height. CONCLUSIONS: The smaller the intercondylar notch
      the smaller the cross-sectional area of the ACL midsubstance. In addition to the
      impingement of the ACL at the anterior and posterior roof of the notch, a
      biomechanically weaker ACL may be the reason for disposition to an ACL rupture in
      patients with a small intercondylar notch. Women have a thinner ACL midsubstance
      than men of the same height which may be one of the critical etiologic factors
      that predispose women to an ACL rupture.

PMID- 16807753
TI  - Reader's letter on: Gorschewsky et al.: the treatment of proximal humeral
      fractures with intramedullary titanium helix wire by 97 patients.

PMID- 16807754
TI  - Influence of anatomy and head position on intranasal drug deposition.
AB  - The objective of this study was to determine the influence of individual
      anatomical differences on intranasal drug deposition. The data of a comparison of
      seven different administration techniques in ten healthy volunteers was used in
      this single-blind crossover pilot study. After intranasal administration of a
      dyed test formulation, endoscopic video imaging was done on seven non-sequential
      days. The deposition pattern per individual around the head of the middle
      turbinate was analyzed for each technique and correlated with the individual
      anatomy. Decreased deposition of dyed test formulation in the target area around
      the head of the middle turbinate was observed in the presence of minor septal
      deviations, narrow nasal valve areas, or inferior turbinate hypertrophy; a
      lateral head position helps to bypass a minor septal deviation. Although results
      are preliminary, we conclude that anatomy and head position are important factors
      in the deposition of topical nasal drugs and may be the key to improving
      individual local nasal (steroid) treatment.

PMID- 16807755
TI  - Infection with virulent and avirulent P. syringae strains differentially affects
      photosynthesis and sink metabolism in Arabidopsis leaves.
AB  - Infection of plants with pathogens leads not only to the induction of defence
      reactions but also to changes in carbohydrate metabolism. In this study, the
      effects of infection by a virulent and an avirulent strain of P. syringae on
      spatio-temporal changes in photosynthesis were compared using chlorophyll
      fluorescence imaging. The maximum PSII quantum yield, effective PSII quantum
      yield and nonphotochemical quenching were decreased in Arabidopsis leaves
      infected with either strain. At the same time, the quantum yield of nonregulated
      energy dissipation was increased. These changes could be detected by chlorophyll
      fluorescence imaging before symptoms were visible by eye. The effects were
      restricted to the vicinity of the infection site and did not spread to uninfected
      areas of the leaf. Qualitatively similar changes in photosynthetic parameters
      were observed in both interactions. Major differences between the responses to
      both strains were evident in the onset and time course of changes. A decrease in
      photosynthesis was detectable already at 3 h only after challenge with the
      avirulent strain while after 48 h the rate of photosynthesis was lower with the
      virulent strain. In contrast to photosynthesis, the regulation of marker genes
      for source/sink relations and the activities of invertase isoenzymes showed
      qualitative differences between both interactions. Inoculation of the virulent
      but not the avirulent strain resulted in downregulation of photosynthetic genes
      and upregulation of vacuolar invertases. The activity of vacuolar invertases
      transiently increased upon infection with the virulent strain but decreased with
      the avirulent strain while extracellular invertase activity was downregulated in
      both interactions.

PMID- 16807756
TI  - MUC6 down-regulation correlates with gastric carcinoma progression and a poor
      prognosis: an immunohistochemical study with tissue microarrays.
AB  - PURPOSE: MUC6 was first discovered by screening a gastric mucosa cDNA library and
      is expressed in the mucous cells of the neck zone and antral glands of the
      stomach. The aim of the present study was to clarify whether down-regulation has
      any clinicopathological or prognostic significance in gastric neoplasia. METHODS:
      Expression of MUC6, MUC5AC and MUC2 was examined using tissue microarrays for
      immunohistochemistry in gastric carcinomas (n = 225), adenomas (n = 40), and
      normal mucosa (n = 89) and compared with clinicopathological parameters and
      survival data. RESULTS: MUC6 expression was lower in gastric carcinomas than in
      adenomas or normal mucosa (P < 0.05) and inversely correlated with tumor size,
      depth of invasion, lymphatic and venous invasion, lymph node metastasis and UICC
      staging (P < 0.05). Positive links with expression of MUC2 and MUC5AC were noted
      (P < 0.05). MUC6 expression was lower in diffuse-type than intestinal-type
      lesions (P < 0.05). Kaplan-Meier analysis indicated that cumulative survival of
      patients with no MUC6 expression was significantly lower than with weak, moderate
      or strong expression in all and even advanced gastric carcinoma (P < 0.05).
      Multivariate analysis showed three independent prognostic factors, depth of
      invasion, lymphatic and venous invasion, to concordantly affect the relationship
      between MUC6 expression and prognosis. CONCLUSIONS: Down-regulation of MUC6 may
      contribute to malignant transformation of gastric epithelial cells and underlie
      the molecular bases of growth, invasion, metastasis and differentiation of
      gastric carcinoma. Altered expression might therefore be employed as an indicator
      of pathobiological behaviors and prognosis of gastric carcinoma.

PMID- 16807758
TI  - Detecting disease gene in DNA haplotype sequences by nonparametric dissimilarity
      test.
AB  - Association studies for complex diseases based on haplotype data have received
      increasing attention in the last few years. A commonly used nonparametric method,
      which takes haplotype structure into consideration, is to use the U-statistic to
      compare the similarities between genetic compositions in the case and control
      populations. Although the method and its variants are convenient to use in
      practice, there are some areas where the tests cannot detect even large
      differences between cases and controls. To overcome this problem and enhance the
      power, we propose a new form of the weighted U-statistic, which directly compares
      the dissimilarity between the haplotype structures in the case and control
      populations. We show that this test statistic is asymptotically a linear
      combination of the absolute values of normal random variables under the null
      hypothesis, and shifts strictly toward the right under the alternative, and
      therefore has no blind areas of detection. Simulation studies indicate that our
      test statistic overcomes the weakness of the existing ones and is robust and
      powerful as well.

PMID- 16807757
TI  - A systematic analysis of disease-associated variants in the 3' regulatory regions
      of human protein-coding genes II: the importance of mRNA secondary structure in
      assessing the functionality of 3' UTR variants.
AB  - In an attempt both to catalogue 3' regulatory region (3' RR)-mediated disease and
      to improve our understanding of the structure and function of the 3' RR, we have
      performed a systematic analysis of disease-associated variants in the 3' RRs of
      human protein-coding genes. We have previously analysed the variants that have
      occurred in two specific domains/motifs of the 3' untranslated region (3' UTR) as
      well as in the 3' flanking region. Here we have focused upon 83 known variants
      within the upstream sequence (USS; between the translational termination codon
      and the upstream core polyadenylation signal sequence) of the 3' UTR. To place
      these variants in their proper context, we first performed a comprehensive survey
      of known cis-regulatory elements within the USS and the mechanisms by which they
      effect post-transcriptional gene regulation. Although this survey supports the
      view that RNA regulatory elements function within the context of specific
      secondary structures, there are no general rules governing how secondary
      structure might exert its influence. We have therefore addressed this question by
      systematically evaluating both functional and non-functional (based upon in vitro
      reporter gene and/or electrophoretic mobility shift assay data) USS variant
      containing sequences against known cis-regulatory motifs within the context of
      predicted RNA secondary structures. This has allowed us not only to establish a
      reliable and objective means to perform secondary structure prediction but also
      to identify consistent patterns of secondary structural change that could
      potentiate the discrimination of functional USS variants from their non
      functional counterparts. The resulting rules were then used to infer potential
      functionality in the case of some of the remaining functionally uncharacterized
      USS variants, from their predicted secondary structures. This not only led us to
      identify further patterns of secondary structural change but also several
      potential novel cis-regulatory motifs within the 3' UTRs studied.

PMID- 16807760
TI  - Severe cardiac hypertrophy and long-term dialysis: the Midwest Pediatric
      Nephrology Consortium study.
AB  - Cross-sectional studies have demonstrated that left ventricular hypertrophy (LVH)
      is common in children on maintenance dialysis. We report the echocardiogram
      results of 17 children from seven centers in the Midwest Pediatric Nephrology
      Consortium who have spent at least 2 years on maintenance dialysis and had three
      consecutive echocardiograms: at initiation of dialysis therapy and 1 and 2 years
      later. The results indicate that LVH is prevalent at the initiation of dialysis
      (82%) and remains both frequent (82%) and severe (59%) after 2 years of
      maintenance dialysis. Normalization of LV geometry was unlikely: the prevalence
      of concentric LVH increased and the prevalence of eccentric LVH did not change
      over time, indicating poor blood pressure and volume status control in these
      patients. We conclude that children on maintenance dialysis are at high risk for
      future cardiovascular disease.

PMID- 16807759
TI  - Association analysis of SOD2 variants with methamphetamine psychosis in Japanese
      and Taiwanese populations.
AB  - SOD2 (superoxide dismutase 2) plays a crucial role in protecting the cells
      against damage caused by free radicals, by catalyzing their detoxification. On
      the other hand, cell damage caused by free radical generation following
      methamphetamine administration has been postulated as one of the possible
      pathophysiological mechanisms for methamphetamine psychosis. Hence, we
      investigated the association of SOD2 polymorphisms with the development of
      methamphetamine psychosis, in two independent populations of Japan and Taiwan. We
      recruited 116 patients with methamphetamine psychosis and 189 controls in Japan,
      and 135 patients with methamphetamine psychosis and 204 controls in Taiwan. The
      methamphetamine group was divided into two clinical subtypes: a transient type of
      psychosis (i.e., good prognosis) and a prolonged type of psychosis (i.e., poor
      prognosis), according to the course of the manifestation of psychosis. With
      reference to the genotypic and allelic frequencies of Ala/Val functional
      polymorphism in exon 2, we found significant differences between individuals with
      prolonged methamphetamine psychosis and control samples from Japan and Taiwan in
      the genotypic (P value 0.014 and 0.016, respectively) and in the allelic (P value
      0.004 and 0.047, respectively) frequencies. Our results suggest that Ala/Val
      polymorphism of the SOD2 gene could be associated with the risk of developing
      methamphetamine psychosis.

PMID- 16807761
TI  - Psychosocial evaluation of candidates for living related kidney donation.
AB  - Living kidney donation has raised practical and ethical questions since renal
      transplantation became possible 50 years ago. Nevertheless, living donors are a
      common source for badly needed organs in the pediatric population. The safety and
      well being of the living donor are important concerns. Among the risks of living
      donation are those of a psychological and social nature. To protect these donor
      interests, psychosocial evaluations of donors are done at some transplant
      centers, but there is a lack of consistency regarding standardization of the
      evaluation, the content of the evaluation, and the role of the interviewer. Goals
      of the overall living donor evaluation for kidney transplantation at The
      Children's Hospital of Philadelphia, and the components of the psychosocial
      evaluation protocol in particular, are presented. The protocol's strengths are
      discussed, including the standardization of evaluations for all potential donors;
      the broad spectrum of psychosocial domains assessed; the psychometric measures
      administered; the systematic handling of negative results and some donors' desire
      to opt out; and the protection of confidentiality. Future directions with regard
      to long-term psychosocial outcomes and research protocols are discussed.

PMID- 16807763
TI  - Urinary tract pathogens and their antimicrobial resistance patterns in Turkish
      children.

PMID- 16807762
TI  - Hypercalciuria in patients with CLCN5 mutations.
AB  - Hypercalciuria is regarded as a characteristic symptom of Dent disease, an X
      linked recessive tubulopathy characterized by low molecular weight (LMW)
      proteinuria, nephrocalcinosis/nephrolithiasis, and progressive renal failure due
      to mutations in the CLCN5 gene. As the presence of hypercalciuria may affect the
      decision to consider a CLCN5 mutation in the differential diagnosis, the
      phenotypic spectrum and the relative frequency of hypercalciuria in patients with
      CLCN5 mutations was determined. We assessed renal calcium excretion in 34 male
      patients with proven CLCN5 mutations, who had been referred because of LMW
      proteinuria and at least one additional symptom of Dent disease. Hypercalciuria
      was defined as renal calcium excretion exceeding 0.1 mmol/kg per day. Data
      obtained were compared with all series of CLCN5-positive patients identified by a
      systematic literature survey. In 7 of our 19 families, at least 1 affected male
      had normal calcium excretion. Hypercalciuria was observed in 22 of 31 patients
      tested (71%) compared to 85 of 90 (94.4%) in series from Europe and North America
      and 74.4% from Japan. LMW proteinuria was present in all CLCN5-positive patients;
      25% of the patients in European and North American series, 45% of the Japanese,
      and 41% in the present series had only two of the four principal symptoms of Dent
      disease. Therefore, a CLCN5 mutation should be considered irrespective of the
      presence of hypercalciuria in a patient with LMW proteinuria and one additional
      symptom of Dent disease.

PMID- 16807764
TI  - Non-lethal fetal toxicity of the angiotensin receptor blocker candesartan.

PMID- 16807765
TI  - Steroid-responsive nephrotic syndrome in a patient with nail-patella syndrome.
AB  - Nail-patella syndrome (NPS) is a rare disorder with autosomal dominant mode of
      inheritance. We report a child with NPS and steroid-responsive, frequently
      relapsing nephrotic syndrome. The child had dystrophic nails, flexion
      contractures of both elbows and normal renal functions. X-rays of the knees and
      pelvis showed hypoplastic patellae and iliac horns. Renal histology was
      unremarkable with mild focal increase in mesangial cellularity compatible with
      minimal change disease. Ultrastructural features of NPS including thickening of
      the glomerular basement membrane with electron-lucent areas were not found.

PMID- 16807766
TI  - PRCC-TFE3 renal cell carcinoma in a boy with a history of contralateral
      mesoblastic nephroma.
AB  - The genetics of renal tumors in children is widely recognized. However, most of
      the studies published to date emphasize the association between Wilms tumor and
      the WT-1 gene. Recently, a unique translocation between the X chromosome and
      chromosome 1 or t(X;1) has been described in several reports of renal cell
      carcinomas (RCCs) diagnosed in children and adolescents that results in PRCC-TFE3
      gene fusion. We report here a 9-year old African-American boy with a history of a
      right congenital mesoblastic nephroma treated with nephrectomy and followed by
      annual checkups. After 9 years, he was diagnosed with a mass at the hilum of the
      left kidney during the work-up of new-onset hypertension. A limited biopsy
      revealed densely hyalinized connective tissue that was initially interpreted to
      be a hyalinized contralateral mesoblastic nephroma. The child received
      chemotherapy, but the mass continued to grow. He underwent a left nephrectomy,
      and the pathology was diagnostic for a clear cell RCC. Chromosomal analysis
      disclosed a t(X;1)(p11.2;q21) translocation, which is known to result in a PRCC
      TFE3 gene fusion. The tumor showed nuclear labeling for TFE3 protein by
      immunohistochemistry, supporting the above diagnosis. He has been on
      hemodialysis, is tumor free, and has not been receiving chemotherapy for 24
      months. This is the first report of a RCC as a second malignant neoplasm in a
      child treated for a congenital mesoblastic nephroma.

PMID- 16807767
TI  - Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by
      chromosomal effectiveness of spectrum energy photons and neutrons.
AB  - The effective dose of combined spectrum energy neutrons and high energy spectrum
      gamma-rays in A-bomb survivors in Hiroshima and Nagasaki has long been a matter
      of discussion. The reason is largely due to the paucity of biological data for
      high energy photons, particularly for those with an energy of tens of MeV. To
      circumvent this problem, a mathematical formalism was developed for the photon
      energy dependency of chromosomal effectiveness by reviewing a large number of
      data sets published in the literature on dicentric chromosome formation in human
      lymphocytes. The chromosomal effectiveness was expressed by a simple
      multiparametric function of photon energy, which made it possible to estimate the
      effective dose of spectrum energy photons and differential evaluation in the
      field of mixed neutron and gamma-ray exposure with an internal reference
      radiation. The effective dose of reactor-produced spectrum energy neutrons was
      insensitive to the fine structure of the energy distribution and was accessible
      by a generalized formula applicable to the A-bomb neutrons. Energy spectra of all
      sources of A-bomb gamma-rays at different tissue depths were simulated by a Monte
      Carlo calculation applied on an ICRU sphere. Using kerma-weighted chromosomal
      effectiveness of A-bomb spectrum energy photons, the effective dose of A-bomb
      neutrons was determined, where the relative biological effectiveness (RBE) of
      neutrons was expressed by a dose-dependent variable RBE, RBE(gamma, D (n)),
      against A-bomb gamma-rays as an internal reference radiation. When the newly
      estimated variable RBE(gamma, D (n)) was applied to the chromosome data of A-bomb
      survivors in Hiroshima and Nagasaki, the city difference was completely
      eliminated. The revised effective dose was about 35% larger in Hiroshima, 19%
      larger in Nagasaki and 26% larger for the combined cohort compared with that
      based on a constant RBE of 10. Since the differences are significantly large, the
      proposed effective dose might have an impact on the magnitude of the risk
      estimates deduced from the A-bomb survivor cohort.

PMID- 16807768
TI  - The influence of various storage conditions on cell viability in amniotic
      membrane.
AB  - Up to now freeze-dried, gamma-sterilised or glycerol-preserved amniotic membranes
      (AMs) have widely been used in the field of ophthalmology and wound care (e.g.
      leg ulcers, burns). After some preservation processes in use, like freeze-drying
      or glycerol-preserving, the cells in the AM are no longer viable. Within this
      study we evaluated the influence of different short-term and long-term storage
      conditions on cell viability in AM. Therefore AMs from cesarean section placentae
      were washed and biopsied to evaluate the microbiological status and to determine
      the viability of the tissue. Additionally, viability under various storage
      conditions was examined by assessment of mitochondrial activity. Preservation
      included temperatures above and below 0 degrees C as well as various media
      compositions. As expected, cell viability in amnion decreases during storage, in
      fact the effect was more pronounced when stored frozen, but the higher viability
      of amnion obtained by storage above 0 degrees C with medium is associated with
      the limitation to a short period of storage of about 28 days. The evaluated
      preservation methods are the basis for future non-clinical in-vivo studies in
      which the possible benefit of amnion as a viable biomaterial in wound healing
      will be investigated.

PMID- 16807769
TI  - Down-regulation of transglutaminase II leads to impaired motility of cancer cells
      by inactivation of the protein kinase, Akt, and decrease of reactive oxygen
      species.
AB  - We employed RNA interference to determine the role of tissue transglutaminase II
      (TGase II) in motility of cancer cells. Down-regulation of TGase II by small
      interfering RNA against TGase II impaired adhesion and motility of HeLa cells by
      decreasing phosphorylation of the protein kinase, Akt, and reactive oxygen
      species (ROS). Over-expression of TGase II showed opposite effects. These results
      suggest potential utility of TGase II for development of therapeutic anti cancer
      vaccine.

PMID- 16807770
TI  - Co-expression of interleukin-6 and human growth hormone in apparently normal
      prostate biopsies that ultimately progress to prostate cancer using low pH, high
      temperature antigen retrieval.
AB  - Prostate cancer is the most common cancer in American men and the second leading
      cause of cancer deaths in this group. Both growth hormone (GH) and the
      inflammatory cytokine interleukin 6 (IL-6) have been implicated in prostate
      cancer progression. Studies in other systems have shown that an increase in GH
      results in an increase in IL-6 also. The current study demonstrated a parallel
      spatial and temporal expression of GH and IL-6 in cells in prostate cancer
      glandular acina cells. This study cannot determine if this expression is
      coincidental or causative, but it seems likely that the increase in GH could
      induce the expression of IL-6, since this is the case in other tissues. Optimal
      labelling for IL-6 in our study was achieved with low pH, high temperature
      antigen retrieval.

PMID- 16807771
TI  - Isolated subvalvular pulmonary stenosis: depiction at whole heart magnetic
      resonance imaging.
AB  - Isolated subvalvular pulmonary stenosis is a rare condition and its morphological
      evaluation is obscure. Whole heart magnetic resonance imaging (MRI) is a new,
      totally non-invasive technique which allows three-dimensional comprehension of
      the cardiac structure. We describe a patient with isolated subvalvular pulmonary
      stenosis, in whom whole heart MRI was useful to detect and evaluate the right
      ventricular outflow obstruction.

PMID- 16807772
TI  - Cardiac magnetic resonance findings in isolated congenital left ventricular
      diverticuli.
AB  - Congenital ventricular diverticulum is a rare cardiac abnormality, frequently
      associated with other cardiac or non-cardiac congenital malformations.
      Clinically, congenital ventricular diverticulum may be asymptomatic or cause
      systemic embolization, heart failure, ventricular rupture, ventricular arrhythmia
      and sudden death. Cardiac magnetic resonance (CMR) can be a useful non-invasive
      and non-ionizing method to confirm the presence, size and extent of left
      ventricular (LV) diverticulum and its tissue characterization. In these reports
      we documented the presence of six diverticuli in patients underwent to CMR for
      other clinical indications. In all the cases, magnetic resonance showed an
      accurate assessment of diverticuli.

PMID- 16807773
TI  - Endovascular repair in management of thoracic aortic aneurysms.
AB  - OBJECTIVE: Aneurysms of the thoracic aorta are still potentially life-threatening
      situations. The conventional operation is still associated with morbidity.
      Endovascular stent graft repair offers an alternative to conventional operation
      for management of aortic diseases. Our aim was to report our experience with
      endovascular stent graft repair of thoracic aortic aneurysms. PATIENTS AND
      METHODS: Between November 2002 and October 2005, endovascular stent graft repair
      was performed in 26 patients: post-traumatic aortic aneurysm (n=4), Type B
      dissection (n=3) and descending thoracic aortic aneurysm (n=19). The deployed
      stent graft systems were Talent-Medtronic (n=14) and Excluder-Gore (n=12).
      RESULTS: Successful deployment of the stent grafts in the appropriate position
      was achieved in all patients. There was neither hospital mortality nor
      paraplegia. Late and non-procedure related death occurred in only one patient
      (3.8%). An average of 40% shrinkage of the aneurysmal space was observed. There
      was no early mortality and endoleaks. The median intensive care unit and hospital
      stay times were 1 and 7 days (range 4-13 days), respectively. Post-operative
      computed tomography scans were obtained in all patients and complete thrombosis
      was observed in the false lumen of dissecan aneurysms (n=3) and sac of saccular
      aneurysms in 25 patients. Mean follow up time was 17.1+/-5.4 months. CONCLUSIONS:
      Endovascular stent graft treatment for treatment of thoracic aorta aneurysm, Type
      B dissection and traumatic disease of the thoracic aorta is technically feasible.
      Although the short and mid-term results are encouraging the long term results
      will determine the future of this treatment.

PMID- 16807774
TI  - Atherosclerosis imaging with intravascular ultrasound. Validating acquisition and
      measurement tools to assure meaningful results.

PMID- 16807775
TI  - Dynamic left ventricular outflow tract obstruction induced by dobutamine stress
      echocardiography leading to myocardial ischemia and infarction.
AB  - Left ventricular outflow tract (LVOT) obstruction occurring during dobutamine
      stress echocardiography (DSE) occurs in approximately 15-20% of patients
      undergoing DSE. The clinical significance and mechanism of LVOT obstruction has
      been debated, but is now generally felt to result from the pharmacological
      effects of dobutamine in increasing inotropy and causing peripheral vasodilation.
      It must be realized that in rare instances, ischemia may occur and lead to wall
      motion abnormalities and eventually myocardial infarction. We present the case of
      a 70-year-old asymptomatic woman who underwent a routine pre-operative cardiac
      stress evaluation and was found to develop a dynamic outflow tract obstruction
      leading to myocardial ischemia and infarction.

PMID- 16807776
TI  - Acquired cardiac hypertrophy with outflow tract obstruction in a patient with
      severe Takayasu arteritis.
AB  - Takayasu arteritis with coronary artery involvement is rare and its association
      with secondary cardiac hypertrophy with severe outflow tract obstruction is not
      common. We describe a case of Takayasu arteritis, diagnosed 10 years ago, whose
      coronary artery involvement and obstructive cardiac hypertrophy are ascertained
      after our investigations.

PMID- 16807777
TI  - Aortic wrap as a novel technique of type I endoleak repair.
AB  - Type I endoleak after endovascular abdominal repair is associated with a high
      risk of aneurysm expansion and rupture. Though type I endoleak can frequently be
      managed with endovascular techniques, in this report we describe a patient whose
      endoleak was refractory to multiple attempts at endovascular repair. The patient
      ultimately underwent a novel minimally invasive surgical repair with placement of
      an aortic wrap around the infrarenal aortic neck, successfully abolishing the
      endoleak.

PMID- 16807778
TI  - Fluorescence enhancement of carbendazim fungicide in cucurbit[6]uril.
AB  - The potential increase in fluorescence of a benzimidazole-type fungicide
      (carbendazim) due to complexation with cucurbit[6]uril is reported. The
      fluorescence of the probe carbendazim in aqueous Na2SO4 solution (pH=7.61) at
      room temperature is found to increase by a maximum factor of approximately 10.0
      and blue-shifted up to approximately 11+/-1 nm with the increase in
      cucurbit[6]uril concentration up to approximately 5 mM. This fluorescence
      enhancement is the result of formation of a 1:1 guest-host inclusion complex, in
      which the guest carbendazim is incorporated inside the hydrophobic cavity of the
      host curbit[6]uril through the amido-ester part. Such mode of inclusion is
      supported by NMR spectral measurements, in which upon encapsulation, the
      resonance of the methyl-protons of the amido-ester moiety is shifted
      significantly to upfield in the (1)H NMR spectrum. Also, to assess the formation
      of inclusion complex, solid samples prepared by co-evaporation have been studied,
      using differential scanning calorimetry (DSC). Measurement of the enhancement as
      a function of cucurbit[6]uril concentrations yielded a value of the equilibrium
      constant (Ka) of 271+/-10 M(-1) at 25 degrees C. From the temperature dependence
      of the equilibrium constants, DeltaH and DeltaS values have been negative in
      sign, indicating the dipole-dipole interactions and the steric factors associated
      with the formation of this inclusion complex. It might be proposed that the
      spectral changes due to the inclusion of carbendazim are the result of decrease
      in the polarity of the surrounded media rather than the loss of carbendazim
      rotational mobility.

PMID- 16807779
TI  - EFA6A-like antibodies in paraneoplastic encephalitis associated with immature
      ovarian teratoma: a case report.
AB  - We describe a 19-year-old patient with paraneoplastic encephalitis associated
      with immature ovarian teratoma (OT), who presented with psychiatric symptoms,
      prolonged disturbance of consciousness, refractory status epilepticus, central
      hypoventilation, and various abnormal involuntary movements. Immunological
      characterization of the patient's serum and cerebrospinal fluid (CSF)
      demonstrated the presence of an autoantibody that colocalized with EFA6A, a brain
      specific protein involved in the regulation of dendritic development of
      hippocampal neurons. Despite the severity of the symptoms, the patient showed
      significant neurological improvement following removal of the tumor and
      chemotherapy. This case suggests that physicians should rule out an OT in young
      women with encephalitis who present with the subacute-onset of psychiatric
      symptoms. Antibodies that colocalize with EFA6A are a valuable marker for early
      diagnosis of a potentially reversible paraneoplastic encephalitis associated with
      OT.

PMID- 16807781
TI  - Intelligence and adaptive function in children diagnosed with brain tumour during
      infancy.
AB  - BACKGROUND: Late effects of treatment in children diagnosed and treated for brain
      tumours in infancy is a major concern. Assessment of infants presenting with
      brain tumours is difficult and there is little information available regarding
      the development of infants prior to treatment and hence the impact of the tumour
      itself on developmental outcomes. AIM: To describe the development of children
      diagnosed with brain tumours in infancy and to document their cognitive and
      adaptive function at school entry. METHOD: Infants were psychologically evaluated
      at the time of diagnosis of a brain tumour and during their fifth or sixth year
      in preparation for school entry. RESULTS: Children diagnosed with brain tumours
      in infancy display developmental delays in a number of areas of adaptive
      function. By the time these children are school age they display further
      compromise in cognitive and academic skills and adaptive behaviour. Higher levels
      of deficit at follow-up were associated with tumour location in the
      supratentorium, younger age at diagnosis and longer time since diagnosis. The
      effect of radiotherapy could not be determined because of differing degrees of
      developmental compromise in the treatment groups at baseline. CONCLUSION: Brain
      tumours in infancy confer a risk of poor developmental progress at the time of
      diagnosis. These children display additional compromise of development by the
      time they reach school age. Research protocols evaluating the impact of treatment
      in infants diagnosed with brain tumours need to take account of the developmental
      status of the child at diagnosis.

PMID- 16807780
TI  - Medical management of patients with brain tumors.
AB  - The most common medical problems in brain tumor patients include the management
      of seizures, peritumoral edema, medication side effects, venous thromboembolism
      (VTE), fatigue and cognitive dysfunction. Despite their importance, there are
      relatively few studies specifically addressing these issues. There is increasing
      evidence that brain tumor patients who have not had a seizure do not benefit from
      prophylactic antiepileptic medications. Patients on corticosteroids are at
      greater risk of Pneumocystis jerovecii pneumonia and may benefit from
      prophylactic therapy. There is also growing evidence suggesting that
      anticoagulation may be more effective than inferior vena cava IVC) filtration
      devices for treating VTE in brain tumor patients and the risk of hemorrhage with
      anticoagulation is relatively small. Low-molecular weight heparin may be more
      effective than coumadin. Medications such as modafinil and methylphenidate have
      assumed an increasing role in the treatment of fatigue, while donepezil and
      memantine may be helpful with memory loss.

PMID- 16807782
TI  - Effectiveness of novel combination chemotherapy, consisting of 5-fluorouracil,
      vincristine, cyclophosphamide and etoposide, in the treatment of low-grade
      gliomas in children.
AB  - Low-grade gliomas (LGG), which account for about 30% of brain tumors in children,
      are usually treated with surgical excision and/or radiotherapy. For patients who
      have significant residual tumor after resection or relapse after radiation, the
      proper chemotherapy regimen has not yet been identified. Thirteen children
      diagnosed with LGG outside the cerebellum between January 1999 and December 2004,
      all of whom had significant residual tumor after surgical resection, relapsed
      after radiation or showed visual deterioration, were treated for 18 months with a
      multi-drug regimen of vincristine, etoposide, cyclophosphamide and 5
      fluorouracil. Of the 7 patients who completed chemotherapy, 1 showed complete
      response (CR), 5 showed partial response (PR), and 1 had stable disease (SD). In
      5 patients, chemotherapy was prematurely discontinued; 4 of these patients showed
      tumor progression and 1 had SD. One patient is still undergoing treatment. The
      side effects of chemotherapy were manageable. The median time to tumor response
      was 34 months (range, 2-82 months). The progression free survival was 67.3%.
      Pediatric LGG patients with residual tumor after surgery or who undergo
      relapse(s) may be successfully treated using our combination chemotherapy
      regimen.

PMID- 16807783
TI  - Angiogenic patterns and their quantitation in high grade astrocytic tumors.
AB  - BACKGROUND: The objectives of this study on high grade astrocytic tumors were (i)
      to establish differences, if any, between grades III & IV tumors among angiogenic
      parameters, both qualitative and quantitative, and (ii) to correlate angiogenic
      parameters with proliferation indices, namely T2a and MIB1 labeling indices.
      DESIGN: Twenty nine consecutive cases of WHO grades III (11) and IV (18)
      astrocytic tumors diagnosed in the year-2004 were studied, using H&E and CD34,
      MIB1 and T2a immunostaining by streptavidin biotin technique. Angiogenic patterns
      were studied and parameters quantitated using Image Pro Plus software (four
      hotspots) on CD34 immunostained sections to determine intratumoral microvessel
      density (iMVD), microvascular area (MVA), aspect, mean diameter (MD) and fractal
      dimension (FD). RESULTS: Main angiogenic patterns of capillary (18) and
      glomeruloid (9) types were best developed in glioblastomas. Statistically
      significant differences (P<0.05) were seen between grades III and IV in iMVD,
      aspect, MD and FD, but not in angiogenic patterns or MVA (P = 0.27).
      Statistically significant differences (P<0.05) were seen between glioblastomas
      with glomeruloid vs. capillary types in iMVD and FD, but not in MVA, aspect and
      mean vessel diameter. T2a values correlated with MIB1 labeling indices (R =
      0.965, P<0.001). Intratumoral endothelial MIB1 LI was significantly higher in
      grade IV as compared to grade III, but did not correlate with angiogenic
      parameters. No correlation of angiogenic patterns and proliferation indices was
      noted (R = -0.221, P = 0.26). Limited follow up data showed all recurrent grade
      IV tumors to be of glomeruloid type. CONCLUSION: Increased angiogenesis in grade
      IV, as compared to grade III, astrocytic tumors is characterized by an increased
      number/density of vessels: an increase in vessels characterized by
      disproportionate lengthening and likely associated with the infiltrative
      properties of the tumors; and an increase in pliable, irregularly shaped or
      structured vessels. In addition, there is a greater frequency of glomeruloid
      structures indicating inadequate directional migration of the newly formed
      vessels. The lack of correlation of these angiogenesis parameters with the MIB1
      and T2a proliferation indices reflects the complexity of angiogenesis parameters
      in high grade gliomas. Further studies are needed to determine the usefulness of
      the angiogenic parameters in the improved diagnosis (grading) and prognosis of
      astrocytic tumors.

PMID- 16807784
TI  - Alzheimer's disease: halothane induces Abeta peptide to oligomeric form--solution
      NMR studies.
AB  - Alzheimer's disease (AD) is a significant contributor to cognitive decline and is
      responsible for about half of the cases of dementia in later life. Although exact
      etiology of AD is not known, however, many risk factors for AD are identified.
      Anesthesia for elderly patients is considered as a risk factor in AD as they
      frequently experience deterioration in cognitive function with long exposure to
      anesthetics during surgery. Inhaled anesthetic agents remain the mainstay for
      patients undergoing major surgical operations. This study using multidimensional
      NMR spectroscopy provides the first direct evidence in vitro that inhaled
      anesthetic, halothane specifically interacts with Abeta40 and Abeta42 peptide.
      Halothane induces structural alternation of Abeta peptide from soluble monomeric
      alpha-helical form to oligomeric beta-sheet conformation, which may hasten the
      onset of AD. Abeta42 is more prone to oligomerization compared to Abeta40 in the
      presence of halothane. The molecular mechanism of halothane induced structural
      alternation of Abeta peptide is discussed.

PMID- 16807785
TI  - Hippocampal neuropathology of diabetes mellitus is relieved by estrogen
      treatment.
AB  - 1. A recently recognized complication of uncontrolled diabetes mellitus is the
      encephalopathy involving, among other regions, the hippocampus. Since estrogens
      bring neuroprotection in cases of brain injury and degenerative diseases, we have
      studied if estradiol (E2) administration counteracts some hippocampal
      abnormalities of streptozotocin (STZ)-diabetic adult mice. 2. We first report the
      ability of E2 to modulate neurogenesis in the dentate gyrus (DG) and
      subventricular zone (SVZ) of diabetic mice. Using bromodeoxyuridine (BrdU) to
      label newly generated cells, a strong reduction in cell proliferation was
      obtained in DG and SVZ of mice sacrificed 20 days after STZ administration. The
      reduction was completely relieved by 10 days of E2 pellet implantation, which
      increased 30-fold the circulating E2 levels. 3. Diabetic mice also showed
      abnormal expression of astrocyte markers in hippocampus. Thus, increased number
      of GFAP(+) cells, indicative of astrogliosis, and increased number of
      apolipoprotein-E (Apo-E)(+) astrocytes, a marker of ongoing neuronal dysfunction,
      was found in stratum radiatum below the CA1 hippocampal subfield of diabetic
      mice. Both parameters were reverted to normal by the E2 regime that upregulated
      cell proliferation. 4. The studies demonstrated that hippocampal neuropathology
      of uncontrolled diabetes is a reversible condition and sensitive to estrogen
      treatment. Studies in animal models may open up new venues for understanding the
      beneficial role of steroid hormones in diabetic encephalopathy.

PMID- 16807786
TI  - Pharmacogenomics: catechol O-methyltransferase to thiopurine S-methyltransferase.
AB  - 1. Pharmacogenomics is the study of the role of inheritance in variation in the
      drug response phenotype-a phenotype that can vary from adverse drug reactions at
      one end of the spectrum to lack of therapeutic efficacy at the other. 2. The
      thiopurine S-methyltransferase (TPMT) genetic polymorphism represents one of the
      best characterized and most clinically relevant examples of pharmacogenomics.
      This polymorphism has also served as a valuable "model system" for studies of the
      ways in which variation in DNA sequence might influence function. 3. The
      discovery and characterization of the TPMT polymorphism grew directly out of
      pharmacogenomic studies of catechol O-methyltransferase (COMT), an enzyme
      discovered by Julius (Julie) Axelrod and his coworkers. 4. This review will
      outline the process by which common, functionally significant genetic
      polymorphisms for both COMT and TPMT were discovered and will use these two
      methyltransferase enzymes to illustrate general principles of pharmacogenomic
      research-both basic mechanistic and clinical translational research-principles
      that have been applied to a series of genes encoding methyltransferase enzymes.

PMID- 16807787
TI  - Induced current bio-impedance technique for monitoring bone mineral density--a
      simulation model.
AB  - In this study, the feasibility of using induced current bio-impedance technique
      as a method to determine and monitor bone mineral density (BMD) was theoretically
      evaluated using computerized simulation model. A 2D polar coordinates numerical
      solver was developed using the Finite Volume Method (FVM) in order to simulate
      the developed potentials over an axial CT cross section of a human thigh. Varying
      femur BMD were simulated by varying femur relative permittivity values. At the
      chosen excitation current of 1 ampere at a frequency of 20 kHz, the real
      component of the surface potential was found to be more sensitive to BMD
      variation than the imaginary component (3.9 microV g(-1) cm3 compared with 0.174
      microV g(-1) cm3). The correlation between varying femur permittivities and the
      real component of the developed surface potential was found to be quadratic and
      influenced by the coil geometry and the measuring point location. Measurement
      sensitivity was improved either by taking the measuring point closer to the femur
      location or by minimizing the distance between the excitation coil and the femur.
      These results provide the basic principle that may enable a future use of bio
      impedance technique for bone density evaluation and monitoring.

PMID- 16807788
TI  - Application of the method of fundamental solutions to potential-based inverse
      electrocardiography.
AB  - Potential-based inverse electrocardiography is a method for the noninvasive
      computation of epicardial potentials from measured body surface
      electrocardiographic data. From the computed epicardial potentials, epicardial
      electrograms and isochrones (activation sequences), as well as repolarization
      patterns can be constructed. We term this noninvasive procedure
      Electrocardiographic Imaging (ECGI). The method of choice for computing
      epicardial potentials has been the Boundary Element Method (BEM) which requires
      meshing the heart and torso surfaces and optimizing the mesh, a very time
      consuming operation that requires manual editing. Moreover, it can introduce mesh
      related artifacts in the reconstructed epicardial images. Here we introduce the
      application of a meshless method, the Method of Fundamental Solutions (MFS) to
      ECGI. This new approach that does not require meshing is evaluated on data from
      animal experiments and human studies, and compared to BEM. Results demonstrate
      similar accuracy, with the following advantages: 1. Elimination of meshing and
      manual mesh optimization processes, thereby enhancing automation and speeding the
      ECGI procedure. 2. Elimination of mesh-induced artifacts. 3. Elimination of
      complex singular integrals that must be carefully computed in BEM. 4. Simpler
      implementation. These properties of MFS enhance the practical application of ECGI
      as a clinical diagnostic tool.

PMID- 16807789
TI  - Cultural competence in interdisciplinary collaborations: a method for respecting
      diversity in research partnerships.
AB  - There is growing recognition of the need by funding agencies, universities, and
      research units for interdisciplinary research to tackle complex societal problems
      that cannot be adequately addressed by single disciplines alone.
      Interdisciplinary collaboration capitalizes on a diversity of perspectives and
      practices that each discipline offers in hopes of providing innovative solutions
      to multifaceted problems. However, for interdisciplinary work to be effective,
      members of the collaboration must recognize that cultural differences exist
      between and within disciplines. This paper conceptualizes disciplines as cultural
      groups and advocates for culturally competent practices to facilitate
      interdisciplinary research and practice. Specifically, each participant in
      interdisciplinary collaborations must value diversity, develop the capacity for
      self-assessment, work towards understanding one's own disciplinary culture, and
      be sensitive to the dynamics inherent when cultures interact. Additionally,
      members of any interdisciplinary endeavor must be cognizant of power dynamics at
      play and avoid such things as tokenism, informal hierarchies, and disciplinary
      policing. Through awareness of one's own disciplinary culture and sensitivity to
      others, interdisciplinary research and practice may provide creative solutions to
      important problems.

PMID- 16807790
TI  - Bridging uncharted waters in Georgia: Down Syndrome Association of Atlanta
      outreach to Latino/a families.
AB  - Receiving the news that your newborn child has Down syndrome is difficult for
      most parents; difficulties which are compounded by language and cultural barriers
      for immigrant Latino/a families. The metro Atlanta area has shown a large
      increase in this population in the last 10 years, and increasing numbers of
      Latino/a parents with children with Down syndrome are coming in contact with the
      health care system. Experiences and observations regarding the formation of a
      Latino/a support group for parents of children with Down syndrome in Atlanta are
      described. In addition, efforts to integrate these Latino/a parents into a parent
      education conference sponsored by the Down Syndrome Association of Atlanta are
      also recounted. Finally, reflections upon the lessons learned and individual and
      organizational changes that occurred as a result of the process are discussed.

PMID- 16807791
TI  - Windows of opportunity: fundamental concepts for understanding alcohol-related
      disparities experienced by young Blacks in the United States.
AB  - This paper presents a theoretical framework for conceptualizing alcohol-related
      disparities experienced by young Blacks in the United States. The framework
      highlights areas of risk and opportunity as they relate to the development of
      alcohol use and alcohol-related problems. In this paper, life course development
      theory serves as a guide for identifying a critical period in the development of
      alcohol-related disparities and it serves to guide the identification of
      opportunities to prevent or attenuate this health outcome. We also highlight
      concepts from ecosocial theory, resilience theory, and prevention science that
      advance our understanding of risk and protective factors for the social problems
      that young Blacks experience related to alcohol use. We conclude with suggestions
      for designing studies that range from etiology to preventive interventions. We
      also recommend methodologies that allow for more nuanced understandings of the
      etiology and prevention of alcohol use and alcohol-related problems experienced
      by young Blacks than have been available to date.

PMID- 16807792
TI  - Reduction of concurrent antipsychotic prescribing practices through the use of
      PSYCKES.
AB  - The New York State Office of Mental Health has implemented the browser based
      Psychiatric Clinical Knowledge Enhancement System (PSYCKES) medication
      application throughout its inpatient system of care. PSYCKES provides detailed
      current medication regimens and histories, as well as medication best practices
      reports at the patient, psychiatrist, ward, and facility levels. South Beach
      Psychiatric Center (SBPC) has made specific use of a best practices report which
      details proportions of caseloads and number of patients on two or more concurrent
      antipsychotic medications. Psychiatrists received extensive application and
      desktop support and individual and group training was conducted. PSYCKES current
      and historical medication regimens were reviewed for individual cases and best
      practices reports were used in psychiatry supervision from January 2004 to March
      2005. SBPC psychiatrists achieved marked reductions in the proportions of their
      caseloads on two or more concurrent antipsychotics. Although we cannot impute
      causality from this pre-post implementation design, the results of this
      evaluation suggest that the use of PSYCKES was effective in reducing such
      regimens for inpatients.

PMID- 16807793
TI  - The kids oneida project: what happened to services when the payment rules
      changed.
AB  - Community-based systems of care may provide high quality, cost-effective
      alternatives to institutional care for children and adolescents. This report
      examines Kids Oneida (KO), a not-for-profit managed care entity established in
      upstate New York in 1998 to serve such children and their families. Changes in
      payment rules that established the program allowed KO to contract with a wide
      array of providers to provide and be reimbursed for non-traditional and formerly
      unreimbursable services, such as mentoring and supervision. By design, emphasis
      was on highly individualized plans of care in which traditional office-based
      services played only a small part. During the first 30 months of KO's operation,
      228 children, whose severity of emotional disturbances was comparable to those of
      children placed in residential treatment centers, had average monthly
      expenditures for first admissions of 2,734 dollars for services and 228 dollars
      for administrative fees. Median length of stay in the program was 13.5 months,
      yielding an estimate of 39,987 dollars for typical length of stay. Length of stay
      and treatment costs were not related to children's gender or race. Length of stay
      was significantly longer for children with diagnoses indicating attention deficit
      hyperactivity disorder and behavior disorders. Treatment costs were significantly
      higher for children with behavior disorders and/or substance use and children who
      had had prior contact with the juvenile justice system.

PMID- 16807794
TI  - Predictors of compliance with the postpartum visit among women living in healthy
      start project areas.
AB  - OBJECTIVES: Few studies have examined factors associated with compliance with a
      postpartum visit (PPV). The identification of such factors is of particular
      importance in populations with high rates of unintended pregnancies and medical
      complications of pregnancy. This study seeks to determine factors associated with
      compliance with a PPV among low-income women in the population served by fourteen
      Healthy Start sites. METHODS: Data from the Healthy Start Survey of Postpartum
      Women were reviewed to identify variables associated with compliance with a PPV
      at or beyond 6 weeks. Multiple logistic regression models were created, based on
      a sociobehavioral model of health services use, to examine which types of factors
      (demographic, social, enabling or need) are most strongly associated with the use
      of a PPV. RESULTS: The study population consisted of survey respondents
      interviewed six weeks or more following delivery. Eighty-five percent of
      respondents had had a PPV at time of interview. In a multiple regression
      analysis, enabling factors such as multiple moves (OR (95% CI)=0.34 (0.18,
      0.67)), trouble understanding the provider (OR (95% CI)=0.65 (0.43, 0.99)) and
      appointment reminders (OR (95% CI)=2.37 (1.40, 4.02)) were most strongly
      associated with a PPV. CONCLUSIONS: This work finds that women with unstable
      housing, transportation barriers, and difficulties communicating with providers
      are at risk for not receiving a PPV. This suggests that access to postpartum
      health services in the Healthy Start communities studied may not be entirely
      equitable. Policies aimed at improving interconception care will need to address
      these barriers to accessing health services.

PMID- 16807795
TI  - Postpollination changes in floral odor in Silene latifolia: adaptive mechanisms
      for seed-predator avoidance?
AB  - Floral odor is a key trait for pollinator attraction in many plants, but may also
      direct antagonists like herbivores to flowers. In this study, we examined how
      floral scent changes after pollination in Silene latifolia, which has a
      specialized relationship with the seed predator Hadena bicruris. We found an
      overall decrease in total scent emission and considerable changes in relative
      amounts of scent compounds after pollination. Lilac aldehydes A and B as well as
      veratrole contributed most to the decrease in scent emission. These three
      compounds are known to be key signals for the attraction of H. bicruris to the
      flowers. A specific downregulation of these compounds may increase the
      reproductive success of the plant by reducing seed predation after pollination.

PMID- 16807796
TI  - Is speeding a form of gambling in adolescents?
AB  - Speeding is a major contributor to motor vehicle accidents, which are the leading
      cause of death in adolescents. This study compares the extent to which
      adolescents with gambling behavior and substance use reported driving over the
      posted speed limits ("speeding"). Florida adolescents ages 13-17 (n = 1051) were
      surveyed, and asked about gambling activities, problems related to gambling,
      substance use, demographic questions, and speeding. Of the 562 respondents who
      were drivers, the gender distribution was 52.1% male and 47.9% female. Of those
      respondents, 76.9% were Caucasian, 6.8% were African American, 10.1% were
      Hispanic, and 6.1% were Native American/Asian/Other. Simple correlation analysis
      revealed that self-reported speeding is significantly related to gambling
      behavior and substance use. When a linear regression model was used, four factors
      showed the most significant influence on self-reported speeding: past year
      gambling tendency, age, trouble with the police due to drinking, and tranquilizer
      usage. Gambling behavior and high-risk speeding (driving >= 10 mph over speed
      limit) also were noted to be positively correlated. Our data indicate a
      relationship between risky driving, gambling, and other risk-taking behaviors in
      adolescents, and support the hypothesis that speeding may be a form of gambling
      behavior in this age group.

PMID- 16807797
TI  - Anger expression and pain: an overview of findings and possible mechanisms.
AB  - A tendency to manage anger via direct expression (anger-out) is increasingly
      recognized as influencing responses to pain. Elevated trait anger-out is
      associated with increased responsiveness to acute experimental and clinical pain
      stimuli, and is generally related to elevated chronic pain intensity in
      individuals with diverse pain conditions. Possible mechanisms for these links are
      explored, including negative affect, psychodynamics, central adipose tissue,
      symptom specific muscle reactivity, endogenous opioid dysfunction, and genetics.
      The opioid dysfunction hypothesis has some experimental support, and
      simultaneously can account for anger-out's effects on both acute and chronic
      pain. Factors which may moderate the anger-out/pain link are described, including
      narcotic use, gender, and genetic polymorphisms. Pain exacerbating effects of
      trait anger-out are contrasted with the apparent pain inhibitory effects of
      behavioral anger expression exhibited in anger-provoking contexts. Conceptual
      issues related to the state versus trait effects of expressive anger regulation
      are discussed.

PMID- 16807798
TI  - Medical and psychosocial predictors of delay in seeking medical consultation for
      breast symptoms in women in a public sector setting.
AB  - We examined demographic, medical and psychosocial factors related to delay in
      seeking medical consultation for breast symptoms. In this cross-sectional survey,
      124 women with breast symptoms attending an outpatient breast surgery clinic in a
      county general hospital completed questionnaires measuring demographic, medical
      and psychosocial variables. Our outcome variable was delay in seeking medical
      consultation. Younger age (p <or= 0.05), less education (p <or= 0.01), absence of
      a lump (p <or= 0.05), lower perceived risk (p <or= 0.001), less spirituality (p
      <or= 0.01), cost (p <or= 0.001) and not wanting to think about breast symptom(s)
      (p <or= 0.05) were related to delay. Multivariate analyses showed absence of a
      breast lump by education interaction (p <or= 0.05), risk perception (p <or=
      0.001), spirituality (p <or= 0.01) and cost (p <or= 0.001) collectively accounted
      for 38.4% of the variance in delay. Health promotion programs targeting low
      income populations should emphasize the importance of breast symptoms other than
      lumps, especially to younger and less educated women.

PMID- 16807799
TI  - Introduction: the role of myoepithelial cells in integration of form and function
      in the mammary gland.

PMID- 16807800
TI  - Intrauterine breast development and the mammary myoepithelial lineage.
AB  - As their name implies, the myoepithelial cells found at the epithelial
      mesenchymal interface of the human mammary gland disclose features suggestive of
      a dual epithelial-like and muscle-like differentiation, i.e. they co-express
      various keratins and vimentin intermediate filaments, as well as smooth muscle
      related antigens. This article provides an overview of the literature on
      intrauterine breast development with special emphasis on the myoepithelial
      component of the fetal human mammary gland epithelium. It discusses original and
      recently published immunohistochemical data on myoepithelial precursors and
      reasserts the relevance of developmental, morphological fetal tissue-based
      studies to the understanding and the clinical management of adult diseases.

PMID- 16807801
TI  - Myoepithelial cells in the control of mammary development and tumorigenesis: data
      from genetically modified mice.
AB  - Until recently, myoepithelial cells-the second major cell population in the
      mammary epithelium-were not considered to play an important role in the
      morphogenetic events during gland development. Mouse mutants with changes in the
      gene expression pattern characteristic of the basal myoepithelial cell layer have
      been generated and used to show that these cells influence the proliferation,
      survival and differentiation of luminal cells, modulate stromal-epithelial
      interactions and actively participate in mammary morphogenesis. Various cellular
      and molecular mechanisms may underlie the observed phenotypes. These include an
      unbalanced expression of matrix degrading metalloproteinases (MMPs) and their
      inhibitors, leading to changes in the composition and organization of the
      (extracellular matrix) ECM, the production of soluble growth factors affecting
      stromal and epithelial cell growth and differentiation and direct signaling
      through cell-cell contacts between the myoepithelial and luminal cell layers.

PMID- 16807802
TI  - Oxytocin receptor signaling in myoepithelial and cancer cells.
AB  - Oxytocin (OT) plays a crucial role as a mediator of breast myoepithelial cell
      contraction, the process responsible for the ejection of milk during lactation,
      and is also involved in myoepithelial cell proliferation and postpartum mammary
      gland proliferation. Furthermore, although a number of breast cancer cells have
      oxytocin receptors (OTRs), it has been reported that OT stimulates, inhibits, or
      has no effect on cell proliferation. As these different effects seem to be
      mediated by different signaling pathways elicited by OTR stimulation, we here
      review the regulation of OTR signaling in different cell systems and discuss how
      understanding the molecular basis of receptor coupling specificity has become
      extremely important for understanding the role played by OTRs in regulating cell
      growth.

PMID- 16807804
TI  - Myoepithelial cells: autocrine and paracrine suppressors of breast cancer
      progression.
AB  - Host cellular paracrine regulation of tumor progression is an important
      determinant of tumor biology but one cell that has been ignored in this
      regulation is the myoepithelial cell. Myoepithelial cells surround normal ducts
      and precancerous lesions, especially of the breast and form a natural border
      separating proliferating epithelial cells from proliferating endothelial cells
      (angiogenesis). Myoepithelial cells may thus negatively regulate tumor invasion
      and metastasis. Whereas epithelial cells are susceptible targets for transforming
      events, myoepithelial cells are resistant. Therefore, it can be said that
      myoepithelial cells function as both autocrine as well as paracrine tumor
      suppressors. Our laboratory has found that myoepithelial cells secrete a number
      of suppressor molecules including high amounts of diverse proteinase inhibitors
      and angiogenic inhibitors but low amounts of proteinases and angiogenic factors
      compared to common malignant cell lines. This observation has been made in vitro,
      in mice, and in humans and suggests that myoepithelial cells exert pleiotropic
      suppressive effects on tumor progression. The gene expression profile of
      myoepithelial cells may explain the pronounced anti-invasive and anti-angiogenic
      effects of myoepithelial cells on carcinoma cells and may also account for the
      reduced malignancy of myoepithelial tumors, which are devoid of appreciable
      angiogenesis and invasive behavior.

PMID- 16807803
TI  - Do myoepithelial cells hold the key for breast tumor progression?
AB  - Mammary myoepithelial cells have been a neglected facet of breast cancer biology,
      largely ignored since they have been considered to be less important for
      tumorigenesis than luminal epithelial cells from which most of breast carcinomas
      are thought to arise. In recent years as our knowledge of stem cell biology and
      the cellular microenvironment has been increasing, myoepithelial cells are slowly
      starting to gain more attention. Emerging data raise the hypothesis whether
      myoepithelial cells play a key role in breast tumor progression by regulating the
      in situ to invasive carcinoma transition and that myoepithelial cells are part of
      the mammary stem cell niche. Paracrine interactions between myoepithelial and
      luminal epithelial cells are known to be important for regulation of cell cycle
      progression, establishing epithelial cell polarity, and inhibiting cell migration
      and invasion. Based on these functions, normal mammary myoepithelial cells have
      been called "natural tumor suppressors." However, during tumor progression
      myoepithelial cells seem to loose these properties, and eventually this cell
      population diminishes as tumors become invasive. Better understanding of
      myoepithelial cell function and their role in tumor progression may lead to their
      exploitation for cancer therapeutic and preventative measures.

PMID- 16807805
TI  - Myoepithelial cells: their origin and function in breast morphogenesis and
      neoplasia.
AB  - The human breast epithelium is a branching ductal system composed of an inner
      layer of polarized luminal epithelial cells and an outer layer of myoepithelial
      cells that terminate in distally located terminal duct lobular units (TDLUs).
      While the luminal epithelial cell has received the most attention as the
      functionally active milk-producing cell and as the most likely target cell for
      carcinogenesis, attention on myoepithelial cells has begun to evolve with the
      recognition that these cells play an active part in branching morphogenesis and
      tumor suppression. A major question that has been the subject of investigation
      pertains to how the luminal epithelial and myoepithelial lineages are related and
      precisely how they arise from a common putative stem cell population within the
      breast. Equally important is the question of how heterotypic signaling occurs
      between luminal epithelial and surrounding myoepithelial cells in normal breast
      morphogenesis and neoplasia. In this review we discuss data from our laboratories
      and from others regarding the cellular origin of human myoepithelial cells, their
      function in maintaining tissue polarity in the normal breast, and their role
      during neoplasia.

PMID- 16807806
TI  - Myoepithelial cells: pathology, cell separation and markers of myoepithelial
      differentiation.
AB  - Until recently the myoepithelial cell has been studied relatively little in terms
      of its role in breast cancer. A number of malignancies showing myoepithelial
      differentiation have been reported in the literature, although they are still
      thought to be relatively rare and only limited studies are published. As a result
      of recent expression profiling experiments, one type of tumor with myoepithelial
      features, the so-called 'basal' breast cancer, has received a renewed interest,
      although it has been known to pathologists for more than two decades. These
      tumors, which express markers of both luminal and myoepithelial cells, are now
      being studied using antibodies against some new molecules that have emerged from
      studies of sorted normal luminal and myoepithelial cells. These
      immunohistochemical data, combined with genomic studies, may lead to better
      identification and management of patients with 'basal' tumors.

PMID- 16807807
TI  - Biomaterials in ophthalmology, 2005.

PMID- 16807808
TI  - Blue light-filtering foldable acrylic intraocular lens.

PMID- 16807809
TI  - Numerical estimation of heat distribution from the implantable battery system of
      an undulation pump LVAD.
AB  - We have been developing an implantable battery system using three series
      connected lithium ion batteries having an energy capacity of 1,800 mAh to drive
      an undulation pump left ventricular assist device. However, the lithium ion
      battery undergoes an exothermic reaction during the discharge phase, and the
      temperature rise of the lithium ion battery is a critical issue for implantation
      usage. Heat generation in the lithium ion battery depends on the intensity of the
      discharge current, and we obtained a relationship between the heat flow from the
      lithium ion battery q(c)(I) and the intensity of the discharge current I as
      q(c)(I) = 0.63 x I (W) in in vitro experiments. The temperature distribution of
      the implantable battery system was estimated by means of three-dimentional finite
      element method (FEM) heat transfer analysis using the heat flow function q(c)(I),
      and we also measured the temperature rise of the implantable battery system in in
      vitro experiments to conduct verification of the estimation. The maximum
      temperatures of the lithium ion battery and the implantable battery case were
      measured as 52.2 degrees C and 41.1 degrees C, respectively. The estimated result
      of temperature distribution of the implantable battery system agreed well with
      the measured results using thermography. In conclusion, FEM heat transfer
      analysis is promising as a tool to estimate the temperature of the implantable
      lithium ion battery system under any pump current without the need for animal
      experiments, and it is a convenient tool for optimization of heat transfer
      characteristics of the implantable battery system.

PMID- 16807810
TI  - In vivo evaluation of the improved MCMS-0102 pacemaker with a rapid pacing mode
      for induction of experimental heart failure in animals.
AB  - The MCMS-0102 cardiac pacemaker for rapid ventricular pacing to induce heart
      failure in animals has been improved in terms of miniaturization and performance.
      To determine the performance of the new MCMS-0102, six devices were implanted in
      beagle dogs, and two of these devices were reimplanted for continued pacing in a
      total of eight beagle dogs. The hearts were paced at 260 beats per minute for 4
      weeks (P group: n = 8). The hemodynamic status of the P group was examined and
      compared with nonpaced dogs (NP group: n = 8). The neurohumoral status of the P
      group was evaluated before and after rapid pacing. Stable operation of the six
      devices during rapid pacing was confirmed using the telemetry system. Postmortem
      examinations revealed features similar to clinical heart failure characterized by
      massive ascites, pleural effusion, cardiomegaly, and liver congestion in all the
      paced dogs. Cardiac output was 1.1 +/- 0.2 l/min in the NP group and 0.5 +/- 0.1
      l/min in the P group (P < 0.0001). The left atrial pressure and the central
      venous pressure of the P group and the NP group were 23 +/- 6 versus 6 +/- 2 mmHg
      (P < 0.0001) and 10 +/- 3 versus 4 +/- 3 mmHg (P < 0.001), respectively. In the
      paced dogs, plasma renin activity increased from 0.5 +/- 0.4 to 8.5 +/- 7.4
      ng/ml/h (P < 0.05) and atrial natriuretic peptide levels increased from 69 +/- 41
      to 229 +/- 72 pg/ml (P < 0.001). The improved MCMS-0102 was successfully
      implanted in beagle dogs and it succeeded in inducing the congestive heart
      failure model.

PMID- 16807811
TI  - Nanopillar sheets as a new type of cell culture dish: detailed study of HeLa
      cells cultured on nanopillar sheets.
AB  - Nanopillar sheets were fabricated with high-aspect ratio structures with a
      diameter of 160-1,000 nm and a height of 1 mum by nanoimprinting. The suitability
      of nanopillar sheets as a new type of cell culture dish was examined by studying
      the behavior of HeLa cells cultured on the sheets using light microscopy,
      scanning electron microscopy, and fluorescence microscopy observing actin and
      vinculin molecules. The nanopillar structure enabled easy subculture of the cells
      from the sheets without conventional trypsinization. Moreover, the HeLa cells
      divided and proliferated on the sheets in a different way to that found on petri
      dish because of the manner in which the cells adhered to the materials.

PMID- 16807812
TI  - Evaluation of blood access dysfunction based on a wavelet transform analysis of
      shunt murmurs.
AB  - We investigated shunt murmurs based on wavelet transform analysis as a new method
      for assessing vascular access function. In the present study, in patients with
      venous stenosis near an arteriovenous fistula (A-V fistula), a sensor was placed
      at different positions around the stenosis and shunt murmur signals obtained
      using a measurement system were subjected to time-frequency analysis based on
      wavelet transforms. The shunt murmurs obtained from the stenotic region closely
      represented some features of murmurs that are often referred to as "high-pitch"
      murmurs in the clinical setting. In contrast, shunt murmurs obtained about 5 cm
      downstream of the stenotic region closely represented some features of murmurs
      that are often referred to as "low-pitch" murmurs in the clinical setting.
      Furthermore, with the aim of extending the lifespan of arteriovenous grafts (A-V
      grafts) by detecting and treating stenotic lesions before the A-V graft becomes
      occluded, we evaluated the possibility of utilizing the present shunt murmur
      analysis for monitoring stenosis in such A-V grafts. When shunt murmurs from
      patients with A-V grafts were analyzed, the results suggested that the blood flow
      through the venous anastomosis of the graft was the most turbulent. This present
      method whereby blood flow in an A-V fistula is assessed based on the frequency
      distribution on a time-frequency plane by wavelet transform analysis is
      advantageous because findings are not markedly affected by sensor attachment.
      Furthermore, because the sensor is attached using an adhesive collar,
      measurements can be taken over a short period of time before each dialysis
      session.

PMID- 16807813
TI  - Development of a highly responsive needle-type glucose sensor using polyimide for
      a wearable artificial endocrine pancreas.
AB  - To produce a long-life, stable, miniature glucose sensor for a wearable
      artificial endocrine pancreas (WAEP), we developed a novel microneedle-type
      glucose sensor using polyimide, designated the PI sensor (outer diameter, 0.3 mm;
      length, 16 mm), and investigated its characteristics in vitro and in vivo. In the
      in vitro study, we tested the sensor in 0.9% NaCl solution with varying glucose
      concentrations and observed an excellent linear relationship between the sensor
      output and glucose concentration (range: 0-500 mg/100 ml). In in vivo
      experiments, the PI sensor was inserted into the abdominal subcutaneous tissue of
      beagle dogs (n = 5), and interstitial fluid glucose concentrations were monitored
      after sensor calibration. Simultaneously, blood glucose concentrations were also
      monitored continuously with another PI sensor placed intravenously. The
      correlation and time delay between subcutaneous tissue glucose (Y) and blood
      glucose concentrations (X: 30-350 mg/100 ml) were Y = 1.03X + 7.98 (r = 0.969)
      and 6.6 +/- 1.2 min, respectively. We applied the new WAEP system/PI sensor and
      an intravenous insulin infusion algorithm developed previously for glycemic
      control in diabetic dogs. The use of the WAEP system resulted in excellent
      glycemic control after an oral glucose challenge of 1.5 g/kg (post-challenge
      blood glucose levels: 176 +/- 18 mg/100 ml at 65 min and 93 +/- 23 mg/100 ml at
      240 min), without any hypoglycemia. Thus, we confirmed that our new PI sensor has
      excellent sensor characteristics in vitro and in vivo. The new WAEP using this
      sensor is potentially suitable for clinical application.

PMID- 16807814
TI  - Femoral arteriovenous fistula: a complication of temporary hemodialysis catheter
      placement.
AB  - The femoral vein is increasingly being used as a temporary route for dual-lumen
      hemodialysis catheter placement because it is thought to be safer than the
      internal jugular or subclavian vein sites. However, several factors preclude the
      wider use of indwelling femoral catheters for hemodialysis, including
      interference with ambulation and concern over bleeding, infection, and deep
      thrombosis. Herein we describe a case of right superficial femoral arteriovenous
      fistula as a complication of the insertion of a dual-lumen hemodialysis catheter
      into the right femoral vein. The arteriovenous fistula was successfully managed
      with surgical vascular repair. From this experience, we emphasize that it is
      important for physicians and nursing staff treating patients with indwelling
      central catheters to exercise vigilance to allow early detection and treatment of
      these potentially serious, albeit rare, complications.

PMID- 16807815
TI  - Infection management in a patient with a left ventricular assist device: a case
      report of long-term cefazolin sodium hydrate administration.
AB  - A 55-year-old woman suffered from a bloodstream infection (Staphylococcus
      aureus), which originated from pump inflow and outflow skin exits, from 4 months
      after a parocorporeal left ventricular assist device (LVAD) had been implanted.
      In addition to local irrigation, repeated administration of a weekly unit of
      cefazolin hydrate was temporarily effective, but fever frequently recurred.
      Because short-term antibiotic administration had limited effectiveness, a much
      longer-term course of cefazolin was begun at 14 months post-LVAD implantation and
      was planned to continue until future transplantation. Unfortunately, the patient
      died from a cerebral embolism at 19 months after LVAD implantation; long-term
      consecutive cefazolin administration had suppressed the infection for over 5
      months without side effects. To treat intractable LVAD-associated bloodstream
      infection, long-term administration of a narrow-spectrum beta-lactam drug is an
      effective option.

PMID- 16807816
TI  - [The ecologic milieu in inpatient treatment].
AB  - OBJECTIVE: Therapeutic milieus can be characterized by interactional qualities
      ("social atmosphere") and by ecological conditions. The paper gives a literature
      review on ecological aspects of the therapeutic milieu. Furthermore, a
      questionnaire is introduced operationalizing and measuring the quality of
      ecological milieus. METHOD: 127 patients of two psychosomatic inpatient units
      were asked to evaluate the ecological milieu at home and in the hospital, using
      the housing milieu questionnaire. RESULTS: Patients rated both the quality of
      their home and of the hospital-milieu rather positive. In a comparison of both
      milieus the patients rated the hospital better in respect to space availability,
      noise, building status, and conflicts with others, while the home milieu gets
      higher ratings for cleanliness, the availability of household devices, and the
      possibility to pursue own interests. The housing milieu questionnaire has a high
      internal consistency (home: Cronbach's alpha=0.82, clinic: Cronbach's alpha=0.83)
      and good retest reliability (home: r=0.895; clinic: r=0.854). CONCLUSIONS: The
      literature review shows that the ecological milieu is an important part of the
      therapeutic milieu and should get more attention in science and practice. The
      housing milieu questionnaire allows to describe ecological aspects of the
      therapeutic milieu. Differences between home and hospital argue for the
      sensitivity of the scale. The questionnaire can be used to analyze the quality of
      ecological aspects of the therapeutic milieu.

PMID- 16807817
TI  - [Persistent dissociation as predictor of posttraumatic stress disorder in
      psychosocial disaster workers].
AB  - BACKGROUND: The author prospectively examined the power of persistent
      dissociation in predicting acute and chronic posttraumatic stress disorder
      symptoms (PTSD) in psychologists, psychotherapists, crisis intervention teams and
      clergymen after a disaster. METHODS: 135 psychosocial disaster workers were
      assessed (6 weeks and 6 months after the catastrophe) with the Acute Stress
      Disorder Scale (ASDS), the Posttraumatic Stress Diagnostic Scale (PDS) and the
      German short version of the Dissociative Experience Scale (FDS-20). Correlational
      analysis and a hierarchical multiple regression analysis were conducted. RESULTS:
      Persistent dissociation and acute stress symptoms were correlated with later
      acute and chronic PTSD diagnosis. Together, persistent dissociation und acute
      stress symptoms accounted for 74 % (m)/36 % (w) of the acute and 58 % (m)/44 %
      (w) of the variance in PTSD symptoms. CONCLUSIONS: The results support that
      persistent dissociation is a main predictor of acute and chronic posttraumatic
      stress symptoms in disaster workers.

PMID- 16807819
TI  - Gibberellin biosynthesis and the regulation of plant development.
AB  - Gibberellins (GAs) form a large family of plant growth substances with distinct
      functions during the whole life cycle of higher plants. The rate of GA
      biosynthesis and catabolism determines how the GA hormone pool occurs in plants
      in a tissue and developmentally regulated manner. With the availability of genes
      coding for GA biosynthetic enzymes, our understanding has improved dramatically
      of how GA plant hormones regulate and integrate a wide range of growth and
      developmental processes. This review focuses on two plant systems, pumpkin and
      Arabidopsis, which have added significantly to our understanding of GA
      biosynthesis and its regulation. In addition, we present models for regulation of
      GA biosynthesis in transgenic plants, and discuss their suitability for altering
      plant growth and development.

PMID- 16807820
TI  - Molecular analysis of brassinosteroid action.
AB  - Brassinosteroids (BRs) are steroidal plant hormones with important regulatory
      roles in various physiological processes, including growth, xylem
      differentiation, disease resistance, and stress tolerance. Several components of
      the BR signal transduction pathway have been identified. The extracellular
      domains of receptor kinases such as BRI1 perceive BRs and transduce the signal
      via intracellular kinase domains. Within the cell further kinases and
      phosphatases determine the phosphorylation status of transcription factors such
      as BES1 and BZR1. These factors mediate major BR effects. Studies of BR-regulated
      genes shed light on the molecular mode of BR action. Genes encoding cell-wall
      modifying enzymes, enzymes of the BR biosynthetic pathway, transcription factors,
      and proteins involved in primary and secondary metabolism are subject to BR
      regulation. Gene expression data also point at interactions with other
      phytohormones and a role of BR in stress responses. This article gives a survey
      of the BR-signaling pathway. Two BR-responsive genes, OPR3 and EXO, are described
      in detail.

PMID- 16807821
TI  - Jasmonate biosynthesis in Arabidopsis thaliana--enzymes, products, regulation.
AB  - Among the plant hormones jasmonic acid and related derivatives are known to
      mediate stress responses and several developmental processes. Biosynthesis,
      regulation, and metabolism of jasmonic acid in Arabidopsis thaliana are reviewed,
      including properties of mutants of jasmonate biosynthesis. The individual
      signalling properties of several jasmonates are described.

PMID- 16807822
TI  - The role of salicylic acid and jasmonic acid in pathogen defence.
AB  - Phytohormones are not only instrumental in regulating developmental processes in
      plants but also play important roles for the plant's responses to biotic and
      abiotic stresses. In particular, abscisic acid, ethylene, jasmonic acid, and
      salicylic acid have been shown to possess crucial functions in mediating or
      orchestrating stress responses in plants. Here, we review the role of salicylic
      acid and jasmonic acid in pathogen defence responses with special emphasis on
      their function in the solanaceous plant potato.

PMID- 16807823
TI  - Integration of abscisic acid signalling into plant responses.
AB  - The phytohormone abscisic acid (ABA) plays a major role as an endogenous
      messenger in the regulation of plant's water status. ABA is generated as a signal
      during a plant's life cycle to control seed germination and further developmental
      processes and in response to abiotic stress imposed by salt, cold, drought, and
      wounding. The action of ABA can target specifically guard cells for induction of
      stomatal closure but may also signal systemically for adjustment towards severe
      water shortage. At the molecular level, the responses are primarily mediated by
      regulation of ion channels and by changes in gene expression. In the last years,
      the molecular complexity of ABA signal transduction surfaced more and more. Many
      proteins and a plethora of "secondary" messengers that regulate or modulate ABA
      responses have been identified by analysis of mutants including gene knock-out
      plants and by applying RNA interference technology together with protein
      interaction analysis. The complexity possibly reflects intensive cross-talk with
      other signal pathways and the role of ABA to be part of and to integrate several
      responses. Despite the missing unifying concept, it is becoming clear that ABA
      action enforces a sophisticated regulation at all levels.

PMID- 16807824
TI  - Many roads lead to "auxin": of nitrilases, synthases, and amidases.
AB  - Recent progress in understanding the biosynthesis of the auxin, indole-3-acetic
      acid (IAA) in Arabidopsis thaliana is reviewed. The current situation is
      characterized by considerable progress in identifying, at the molecular level and
      in functional terms, individual reactions of several possible pathways. It is
      still too early to piece together a complete picture, but it becomes obvious that
      A. thaliana has multiple pathways of IAA biosynthesis, not all of which may
      operate at the same time and some only in particular physiological situations.
      There is growing evidence for the presence of an indoleacetamide pathway to IAA
      in A. thaliana, hitherto known only from certain plant-associated bacteria, among
      them the phytopathogen Agrobacterium tumefaciens.

PMID- 16807825
TI  - Auxin biosynthesis in maize.
AB  - For the biosynthesis of the phytohormone indole-3-acetic acid (IAA), a number of
      tryptophan-dependent and -independent pathways have been discussed. Maize is an
      appropriate model system to analyze IAA biosynthesis particularly because high
      quantities of IAA conjugates are stored in the endosperm. This allowed precursor
      feeding experiments in a kernel culture system followed by retrobiosynthetic NMR
      analysis, which strongly suggested that tryptophan-dependent IAA synthesis is the
      predominant route for auxin biosynthesis in the maize kernel. Two nitrilases
      ZmNIT1 and ZmNIT2 are expressed in seeds. ZmNIT2 efficiently hydrolyzes indole-3
      acetonitrile (IAN) to IAA and thus could be involved in auxin biosynthesis.
      Redundant pathways, e.g., via indole-3-acetaldehyde could imply that multiple
      mutants will be necessary to obtain IAA-deficient plants and to conclusively
      identify relevant genes for IAA biosynthesis.

PMID- 16807826
TI  - Indole-3-acetic acid protein conjugates: novel players in auxin homeostasis.
AB  - Indole-3-acetic acid (IAA) is found in plants in both free and conjugated forms.
      Within the group of conjugated IAA there is a unique class of proteins and
      peptides where IAA is attached directly to the polypeptide structure as a
      prosthetic group. The first gene, IAP1, encoding for a protein with IAA as a
      prosthetic group, was cloned from bean (Phaseolus vulgaris). It was shown that
      the expression of IAP1 as a major IAA modified protein in bean seed (PvIAP1) was
      correlated to a developmental period of rapid growth during seed development.
      Moreover, this protein underwent rapid degradation during germination. Since
      further molecular analysis was difficult in bean, the IAP1 gene was transformed
      into Arabidopsis thaliana and Medicago truncatula. Expression of the bean IAP1
      gene in both plant species under the control of its native promoter targeted
      protein expression to the seeds. In Arabidopsis no IAA was found to be attached
      to PvIAP1. These results show that there is specificity to protein modification
      by IAA and suggests that protein conjugation may be catalyzed by species specific
      enzymes. Furthermore, subcellular localization showed that in Arabidopsis PvIAP1
      was predominantly associated with the microsomal fraction. In addition, a related
      protein and several smaller peptides that are conjugated to IAA were identified
      in Arabidopsis. Further research on this novel class of proteins from Arabidopsis
      will both advance our knowledge of IAA proteins and explore aspects of auxin
      homeostasis that were not fully revealed by studies of free IAA and lower
      molecular weight conjugates.

PMID- 16807827
TI  - How does auxin enhance cell elongation? Roles of auxin-binding proteins and
      potassium channels in growth control.
AB  - Elongation growth and a several other phenomena in plant development are
      controlled by the plant hormone auxin. A number of recent discoveries shed light
      on one of the classical problems of plant physiology: the perception of the auxin
      signal. Two types of auxin receptors are currently known: the AFB/TIR family of F
      box proteins and ABP1. ABP1 appears to control membrane transport processes (H+
      secretion, osmotic adjustment) while the TIR/AFBs have a role in auxin-induced
      gene expression. Models are proposed to explain how membrane transport (e.g., K+
      and H+ fluxes) can act as a cross-linker for the control of more complex auxin
      responses such as the classical stimulation of cell elongation.

PMID- 16807828
TI  - Ion channels meet auxin action.
AB  - The regulation of cell division and elongation in plants is accomplished by the
      action of different phytohormones. Auxin as one of these growth regulators is
      known to stimulate cell elongation growth in the aerial parts of the plant. Here,
      auxin enhances cell enlargement by increasing the extensibility of the cell wall
      and by facilitating the uptake of osmolytes such as potassium ions into the cell.
      Starting in the late 1990s, the auxin regulation of ion channels mediating K+
      import into the cell has been studied in great detail. In this article we will
      focus on the molecular mechanisms underlying the modulation of K+ transport by
      auxin and present a model to explain how the regulation of K+ channels is
      involved in auxin-induced cell elongation growth.

PMID- 16807829
TI  - Noise yields order--auxin, actin, and polar patterning.
AB  - Plant patterns have to integrate environmental cues and to cope with a high level
      of noise in the sensory outputs of individual cells. In the first part of this
      review, we demonstrate that local self-amplification linked to lateral inhibition
      can meet this requirement. In the second part, we describe the search for
      candidates for such self-amplification loops in the context of auxin-dependent
      cell growth using Graminean coleoptiles as a model. Auxin-dependent
      reorganization of actin microfilaments interfered with the auxin sensitivity of
      growth. Auxin might control the intracellular transport of factors important for
      auxin sensing via the actomyosin system. By means of a rice mutant with elevated
      auxin responsiveness, we identified an auxin response factor (OSARF1), whose
      expression is upregulated by auxin as a second candidate for a self-amplification
      loop. We studied the cross-talk between auxin signalling and environmental cues
      in the rice mutant hebiba, where the photoinhibition of growth is impaired. We
      found that jasmonate plays a central role in this cross-talk correlated to a
      downregulation of auxin responsiveness. To obtain an insight into auxin-dependent
      coordination, we analyzed a tobacco cell line with axial cell divisions. By a
      combination of modelling and physiological manipulation, we could demonstrate
      that auxin synchronizes the divisions of adjacent cells on the background of
      strong heterogeneity of individual cells. We conclude that self-amplification of
      auxin signalling coupled to mutual competition for available auxin provides a
      versatile tool to fulfill the special requirements posed by patterning in plants.

PMID- 16807830
TI  - New insights into the biology of cytokinin degradation.
AB  - A survey of recent results is presented concerning the role of cytokinin
      degradation in plants, which is catalyzed by cytokinin oxidase/dehydrogenase
      (CKX) enzymes. An overview of Arabidopsis CKX gene expression suggests that their
      differential regulation by biotic and abiotic factors contributes significantly
      to functional specification. Here, we show using reporter gene and
      semiquantitative RT-PCR analyses regulation of individual CKX genes by cytokinin,
      auxin, ABA, and phosphate starvation. Partially overlapping expression domains of
      CKX genes and cytokinin-synthesizing IPT genes in meristematic tissues and endo
      reduplicating cells lend support for a locally restricted function of cytokinin.
      On the other hand, their expression in vascular tissue suggests a function in
      controlling transported cytokinin. Recent studies led to a model for the
      biochemical reaction mechanism of CKX-mediated catalysis, which was refined on
      the basis of the three-dimensional enzyme structure. Last but not least, the
      developmental functions of CKX enzymes are addressed. The recent identification
      of the rice OSCKX2 gene as an important novel breeding tool is highlighted.
      Together the results corroborate the relevance of metabolic control in
      determining cytokinin activity.

PMID- 16807831
TI  - Moss biology and phytohormones--cytokinins in Physcomitrella.
AB  - Mosses present several advantages for the analysis of phytohormone physiology.
      Their enormous regeneration capacity, the possibility of controlling their whole
      life cycle under in vitro culture conditions, as well as the small number of cell
      types facilitate studies of hormone homeostasis. This review focuses on the
      metabolism and biosynthesis of cytokinins, mostly summarising data obtained using
      the moss Physcomitrella patens (Hedw.) B.S.G. which has served as a model system
      for cytokinin research for many years. A comparison of metabolic differences with
      respect to seed plants is presented, pointing out an important role of adenosine
      kinase for the formation of nucleotides during cytokinin interconversion in
      Physcomitrella. Results on cytokinin biosynthesis in Physcomitrella are
      summarised with respect to the OVE mutants, which can be considered unique in the
      plant kingdom due to their strong overproduction of cytokinins. The OVE phenotype
      is correlated with both increased activity in early stages of cytokinin
      biosynthesis as well as increased conversion of cytokinin riboside to the base.
      Cytokinin interconverting reactions can contribute to the increased levels of
      cytokinins in OVE mutants. Further studies on hormone physiology in moss will
      help to complete our understanding of hormonal homeostasis by elucidating the
      situation in an evolutionary early embryophyte.

PMID- 16807832
TI  - Crosstalk between auxin, cytokinins, and sugars in the plant cell cycle.
AB  - Plant meristems are utilization sinks, in which cell division activity governs
      sink strength. However, the molecular mechanisms by which cell division activity
      and sink strength are adjusted to a plant's developmental program in its
      environmental setting are not well understood. Mitogenic hormonal as well as
      metabolic signals drive and modulate the cell cycle, but a coherent idea of how
      this is accomplished, is still missing. Auxin and cytokinins are known as
      endogenous mitogens whose concentrations and timing, however, can be externally
      affected. Although the sites and mechanisms of signal interaction in cell cycle
      control have not yet been unravelled, crosstalk of sugar and phytohormone signals
      could be localized to several biochemical levels. At the expression level of cell
      cycle control genes, like cyclins, Cdks, and others, synergistic but also
      antagonistic interactions could be demonstrated. Another level of crosstalk is
      that of signal generation or modulation. Cytokinins affect the activity of
      extracellular invertases and hexose-uptake carriers and thus impinge on an
      intracellular sugar signal. With tobacco BY-2 cells, a coordinated control of
      cell cycle activity at both regulatory levels could be shown. Comparison of the
      results obtained with the root cell-representing BY-2 cells with literature data
      from shoot tissues or green cell cultures of Arabidopsis and Chenopodium suggests
      opposed and tissue-specific regulatory patterns of mitogenic signals and signal
      crosstalk in root and shoot meristems.

PMID- 16807833
TI  - Moss systems biology en route: phytohormones in Physcomitrella development.
AB  - The moss Physcomitrella patens has become a powerful model system in modern plant
      biology. Highly standardized cell culture techniques, as well as the necessary
      tools for computational biology, functional genomics and proteomics have been
      established. Large EST collections are available and the complete moss genome
      will be released soon. A simple body plan and the small number of different cell
      types in Physcomitrella facilitate the study of developmental processes. In the
      filamentous juvenile moss tissue, developmental decisions rely on the
      differentiation of single cells. Developmental steps are controlled by distinct
      phytohormones and integration of environmental signals. Especially the
      phytohormones auxin, cytokinin, and abscisic acid have distinct effects on early
      moss development. In this article, we review current knowledge about phytohormone
      influences on early moss development in an attempt to fully unravel the complex
      regulatory signal transduction networks underlying the developmental decisions of
      single plant cells in a holistic systems biology approach.

PMID- 16807835
TI  - Nosocomial infections caused by Acinetobacter baumannii: a major threat
      worldwide.

PMID- 16807836
TI  - Retrospective analysis of multidrug-resistant Acinetobacter baumannii strains
      isolated during a 4-year period in a university hospital.
AB  - OBJECTIVE: To describe the epidemiology of Acinetobacter baumannii infection
      during 2000-2003 and to determine whether the multidrug-resistant strains were
      already present in our Toulouse hospital before the 2003 French national
      outbreak. DESIGN: Descriptive molecular and clinical epidemiologic study of A.
      baumannii isolates using a combination of antibiotyping and pulsed-field gel
      electrophoresis (PFGE). SETTING: A 1,000-bed university hospital in Toulouse,
      France. METHODS: All clinical samples that had tested positive for A. baumannii
      between January 1, 2000, and December 31, 2003, were collected. Multidrug
      resistant isolates of A. baumannii were then submitted to PFGE, and clinical
      characteristics of the source patients were noted. RESULTS: A total of 1,277 A.
      baumannii samples were identified, 791 of which had not been previously
      identified; 148 were positive for multidrug-resistant strains. These strains were
      more likely to have been isolated in the intensive care unit (ICU) than were
      susceptible strains (P<.001; relative hazard, 3.77). The positive clinical
      samples were of various types (eg, nonprotected respiratory samples [43%] and
      blood [5%]), but no difference in type of source was seen between resistant and
      susceptible strains. A simultaneous analysis of pulsotypes and antibiotypes
      proved that the outbreak in the ICU in 2003 could be linked to an initially
      endemic clone that had been isolated in 2001. Furthermore, a second clone
      responsible for an extended-spectrum beta -lactamase phenotype was sporadically
      present in our institution. Although the strains isolated in the burn unit were
      also genetically related one to another, the specific responsible clone only
      appeared in 2003. CONCLUSION: Several multidrug-resistant clones can coexist
      endemically for several years and can be detected during an outbreak by close
      survey of epidemic sources.

PMID- 16807837
TI  - Control of an outbreak of multidrug-resistant Acinetobacter baumannii
      calcoaceticus colonization and infection in an intensive care unit (ICU) without
      closing the ICU or placing patients in isolation.
AB  - OBJECTIVE: To describe the control of multidrug-resistant Acinetobacter baumannii
      calcoaceticus (MDRABC) colonization and infection in an intensive care unit
      (ICU). SETTING: An 18-bed ICU in a large tertiary care teaching hospital in
      London. INTERVENTIONS: After recognition of the outbreak, a range of infection
      control measures were introduced over several months that were primarily aimed at
      reducing environmental contamination with the outbreak strain. Strategies
      included use of a closed tracheal suction system for all patients receiving
      mechanical ventilation, use of nebulized colistin for patients with evidence of
      mild to moderate ventilator-associated pneumonia, improved availability of
      alcohol for hand decontamination, and clearer designation of responsibilities and
      strategies for cleaning equipment and the environment in the proximity of
      patients colonized or infected with MDRABC. RESULTS: The outbreak lasted from
      June 2001 through November 2002 and involved 136 new cases of MDRABC infection or
      colonization. The number of newly diagnosed cases per month reached a maximum of
      15 in February 2002, and the number of new cases slowly decreased over the next 9
      months. CONCLUSION: This outbreak was controlled by emphasizing the control of
      environmental reservoirs and did not require recourse to ward closure or
      placement of affected patients in isolation.

PMID- 16807838
TI  - Acinetobacter skin colonization of US Army Soldiers.
AB  - OBJECTIVE: To evaluate whether skin colonization with Acinetobacter calcoaceticus
      baumannii complex exists in a population of healthy, nondeployed US Army soldiers
      and, if present, how it might relate to the infections seen in current war
      casualties. DESIGN: We sampled various skin sites of soldiers to test for the
      presence of A. calcoaceticus-baumannii complex and to establish the prevalence of
      colonization. We then used ribotyping and antimicrobial susceptibility profiles
      to compare the isolates we recovered with A. calcoaceticus-baumannii complex
      isolates from injured soldiers. SETTING: Fort Sam Houston, Texas. PARTICIPANTS: A
      population of healthy, nondeployed US Army soldiers in training. RESULTS: A total
      of 17% of healthy soldiers were found to harbor A. calcoaceticus-baumannii
      complex. However, the strains differed from those recovered from injured
      soldiers. CONCLUSIONS: Skin carriage of A. calcoaceticus-baumannii complex exists
      among soldiers before deployment. However, the difference in the strains isolated
      from healthy soldiers, compared with the strains from injured soldiers, makes it
      difficult to identify skin colonization as the source of infection.

PMID- 16807839
TI  - A multicenter intervention to prevent catheter-associated bloodstream infections.
AB  - BACKGROUND: Education-based interventions can reduce the incidence of catheter
      associated bloodstream infection. The generalizability of findings from single
      center studies is limited. OBJECTIVE: To assess the effect of a multicenter
      intervention to prevent catheter-associated bloodstream infections. DESIGN: An
      observational study with a planned intervention. SETTING: Twelve intensive care
      units and 1 bone marrow transplantation unit at 6 academic medical centers.
      PATIENTS: Patients admitted during the study period. INTERVENTION: Updates of
      written policies, distribution of a 9-page self-study module with accompanying
      pretest and posttest, didactic lectures, and incorporation into practice of
      evidence-based guidelines regarding central venous catheter (CVC) insertion and
      care. MEASUREMENTS: Standard data collection tools and definitions were used to
      measure the process of care (ie, the proportion of nontunneled catheters inserted
      into the femoral vein and the condition of the CVC insertion site dressing for
      both tunneled and nontunneled catheters) and the incidence of catheter-associated
      bloodstream infection. RESULTS: Between the preintervention period and the
      postintervention period, the percentage of CVCs inserted into the femoral vein
      decreased from 12.9% to 9.4% (relative ratio, 0.73; 95% confidence interval [CI],
      0.61-0.88); the total proportion of catheter insertion site dressings properly
      dated increased from 26.6% to 34.4% (relative ratio, 1.29; 95% CI, 1.17-1.42),
      and the overall rate of catheter-associated bloodstream infections decreased from
      11.2 to 8.9 infections per 1,000 catheter-days (relative rate, 0.79; 95% CI, 0.67
      0.93). The effect of the intervention varied among individual units. CONCLUSIONS:
      An education-based intervention that uses evidence-based practices can be
      successfully implemented in a diverse group of medical and surgical units and
      reduce catheter-associated bloodstream infection rates.

PMID- 16807840
TI  - The importance of addressing multidrug resistance and not assuming single-drug
      resistance in case-control studies.
AB  - BACKGROUND: Case-control studies analyzing antibiotic exposure as a risk factor
      for antimicrobial resistance usually assume single-drug resistance in the
      bacteria under study, even though resistance to multiple antimicrobials may be
      present. Since antibiotic selection pressures differ depending on the
      susceptibility profile of the antimicrobial-resistant bacteria, an accurate
      assessment of whether exposure to an individual antimicrobial is a risk factor
      for the emergence of resistance should distinguish between single-drug-resistant
      and multidrug-resistant bacteria. OBJECTIVE: To determine whether the exposures
      to individual antibiotics that were identified as independent risk factors in
      case-control studies differed depending on whether single-drug-resistant or
      multidrug-resistant bacteria were evaluated. DESIGN: Two retrospective case
      control studies were performed with data on patients harboring Pseudomonas
      aeruginosa strains resistant only to ciprofloxacin (CRPA) and patients harboring
      P. aeruginosa strains resistant to ciprofloxacin and other antibiotics (multidrug
      resistant P. aeruginosa [MDR-PA]). These 2 groups were compared with patients not
      harboring P. aeruginosa. SETTING: Two tertiary care hospitals. RESULTS: A total
      of 41 patients harboring CRPA and 151 patients harboring MDR-PA were identified
      and matched to 192 control subjects. By conditional logistic regression,
      independent risk factors associated with presence of CRPA were nonambulatory
      status (OR, 5.6 [95% confidence interval {CI}, 1.4-23]; P=.02) and prior
      ciprofloxacin exposure (OR, 5.0 [95% CI, 1.2-21]; P=.03). Independent risk
      factors for presence of MDR-PA were a Charlson score greater than 2 (OR, 3.3 [95%
      CI 1.8-6.0]; P<.001) and exposure to quinolones (OR, 2.8 [95% CI, 1.2-5.0];
      P=.001), third- and fourth-generation cephalosporins (OR, 3.5 [95% CI, 1.7-7.1];
      P<.001), imipenem (OR, 3.8 [95% CI, 1.2-12.1]; P=.02), and/or aminoglycosides
      (OR, 2.3 [95% CI, 1.04-5.1]; P=.04). CONCLUSION: There were substantial
      differences in exposure to individual antimicrobials between patients harboring
      CRPA and patients harboring MDR-PA. Future case-control studies addressing risk
      factors for single-drug-resistant bacteria should consider the complete
      susceptibility profile of the bacteria under investigation.

PMID- 16807841
TI  - Acquisition of multidrug-resistant organisms among hospital patients hospitalized
      in beds adjacent to critically ill patients.
AB  - OBJECTIVE: To assess whether patients hospitalized in beds physically adjacent to
      critically ill patients are at increased risk to acquire multidrug-resistant
      pathogens. DESIGN: Cohort study.Setting. Shaare Zedek Medical Center, a 550-bed
      medical referral center. PATIENTS: From April to September 2004, we enrolled
      consecutive newly admitted patients who were hospitalized in beds adjacent to
      either mechanically ventilated patients or patients designated as "do not
      resuscitate" (DNR). For each of these patients, we also enrolled a control
      patient who was not hospitalized in a bed adjacent to a critically ill patient.
      We collected specimens from the anterior nares, the oral cavity, and the perianal
      zone at the time of admission and subsequently at 3-day intervals until discharge
      or death. Specimens were cultured on selective media to detect growth of
      antibiotic-resistant pathogens, including Acinetobacter baumannii, methicillin
      resistant Staphylococcus aureus (MRSA), extended-spectrum beta lactamase (ESBL)
      producing Enterobacteriaceae, and vancomycin-resistant enterococci (VRE).
      RESULTS: We enrolled 46 neighbor-control pairs. Among neighbors and controls,
      respectively, the incidence rates for isolation of A. baumannii was 8.3 and 4
      isolations per 100 patient-days (relative risk [RR], 2.1 [95% confidence interval
      {CI}, 0.8-5.2]; P=.12), the incidence rates for MRSA were 1.4 and 2.6 isolations
      per 100 patient-days (RR, 0.6 [95% CI, 0.1-2.3]; P=.45), the incidence rates for
      ESBL-producing Enterobacteriaceae were 10.5 and 9 isolations per 100 patient-days
      (RR, 1.2 [95% CI, 0.6-2.4]; P=.84), the incidence rates for VRE were 4.3 and 4.8
      isolations per 100 patient-days (RR, 0.9 [95% CI, 0.3-2.4]; P=1), and the
      composite incidence rate was 21.7 and 16.2 isolations per 100 patient-days (RR,
      1.3 [95% CI, 0.8-2.3]; P=0.3). CONCLUSIONS: In this pilot study, we did not
      detect an increased incidence rate of isolation of multidrug-resistant pathogens
      among patients hospitalized in beds adjacent to critically ill patients. Further
      studies with larger samples should be conducted in order to generate valid data
      and provide patients, physicians, and policy makers with a sufficient knowledge
      base from which decisions can be made.

PMID- 16807842
TI  - Comparison of unit-specific and hospital-wide antibiograms: potential
      implications for selection of empirical antimicrobial therapy.
AB  - OBJECTIVE: To identify differences between unit-specific and hospital-wide
      antibiograms and to determine the potential impact of these differences on
      selection of empirical antimicrobial therapy. SETTING: A 625-bed tertiary care
      medical center. METHODS: Antimicrobial susceptibility results were collected for
      all inpatient clinical bacterial isolates recovered over a 3-year period;
      isolates were categorized by the hospital location of the patient at the time of
      sampling and by the anatomic site from which the isolate was recovered.
      Antibiograms from each unit were compiled for the most commonly isolated
      organisms and were compared to the hospital-wide antibiogram. RESULTS: A total of
      9,970 bacterial isolates were evaluated in this study, including 2,646
      enterococcal isolates, 2,806 S. aureus isolates, 2,795 E. coli isolates, and
      1,723 Pseudomonas aeruginosa isolates. The percentages of bacterial isolates
      resistant to antimicrobials were significantly higher in the medical ICU and
      surgical ICU than the hospital-wide antibiogram would have predicted, whereas the
      percentages of isolates susceptible to antimicrobials were significantly higher
      in the non-ICU units, compared with the hospital overall. However, on general
      medicine units, the prevalence of susceptibility to levofloxacin was
      significantly lower than that for the hospital overall. CONCLUSIONS: Unit
      specific antibiograms are important for making informed decisions about empirical
      antimicrobial therapy, because the hospital-wide antibiogram may mask important
      differences in susceptibility rates across different units. These differences may
      have important implications for selecting the optimal empirical antimicrobial
      therapy.

PMID- 16807844
TI  - Antibiotic-stewardship practices at top academic centers throughout the United
      States and at hospitals throughout Massachusetts.
AB  - OBJECTIVE: Improvements in antibiotic prescribing to reduce bacterial resistance
      and control hospital costs is a growing priority, but the way to accomplish this
      is poorly defined. Our goal was to determine whether certain antibiotic
      stewardship interventions were universally instituted and accepted at top US
      academic centers and to document what interventions, if any, are used at both
      teaching and community hospitals within a geographic area. DESIGN: Two surveys
      were conducted. In survey 1, detailed phone interviews were performed with the
      directors of antibiotic stewardship programs at 22 academic medical centers that
      are considered among the best for overall medical care in the United States or as
      leaders in antibiotic stewardship programs. In survey 2, teaching and community
      hospitals throughout Massachusetts were surveyed to ascertain what antibiotic
      oversight program components were present. RESULTS: In survey 1, each of the 22
      participating hospitals had instituted interventions to improve antibiotic
      prescribing, but none of the interventions were universally accepted as essential
      or effective. In survey 2, of 97 surveys that were mailed to prospective
      participants, a total of 54 surveys from 19 teaching hospitals and 35 community
      hospitals were returned. Ninety-five percent of the teaching hospitals had a
      restricted formulary, compared with 49% of the community hospitals, and 89% of
      teaching hospitals had an antibiotic approval process, compared with 29% of
      community hospitals. CONCLUSION: There was great variability among the approaches
      to the oversight of antibiotic prescribing at major academic hospitals.
      Antibiotic management interventions were lacking in more than half of the
      Massachusetts community hospitals surveyed. More research is needed to define the
      best antibiotic stewardship interventions for different hospital settings.

PMID- 16807843
TI  - Inaccurate communications in telephone calls to an antimicrobial stewardship
      program.
AB  - BACKGROUND: Antimicrobial stewardship programs (ASPs) decrease unnecessary
      antimicrobial use, decrease antimicrobial resistance, and improve patient
      outcomes. The effectiveness of a prior approval system--that is, the requirement
      that approval be obtained from ASP practitioners before certain antimicrobials
      can be used--depends on the accuracy of the patient data communicated from the
      primary service. OBJECTIVES: To determine the incidence of inaccurate
      communication of patient data during ASP interactions, describe examples of
      inaccurate communications, and identify risk factors for inaccurate
      communication. DESIGN: We used a retrospective cohort design. We evaluated the
      communicated patient data for clinically important inaccuracies, using the
      patients' medical records as the gold standard. SETTING: A tertiary care medical
      center that has a prior approval system for restricted antimicrobials. PATIENTS:
      Inpatients discussed in telephone ASP interactions. INTERVENTION: Observational
      study. RESULTS: Of telephone calls requesting prior approval from ASP
      practitioners, 39% (95% confidence interval [CI], 31%-48%) contained an
      inaccuracy in at least 1 type of patient data (eg, current antimicrobial
      therapy); the incidence varied widely between data types. Examples of
      inaccuracies are given to demonstrate their clinical relevance. In multivariable
      analysis, inaccurate communications were more common for telephone calls from
      surgical services (versus calls from nonsurgical services: odds ratio, 2.1 [95%
      CI, 1.1-3.9]) and for calls received by Infectious Diseases fellows (versus
      pharmacists: odds ratio, 2.0 [95% CI, 1.1-3.8]). CONCLUSIONS: A high proportion
      of ASP calls requesting prior approval included patient data inaccuracies, which
      have the potential to affect the prescribing of antimicrobials. Although risk
      factors were identified, these communication errors were common across the
      different types of ASP interactions. Inaccurate communications may compromise the
      utility of ASPs that use a prior approval system for optimizing antimicrobial
      use.

PMID- 16807845
TI  - A Web-based course on infection control for physicians in training: an
      educational intervention.
AB  - OBJECTIVE: To evaluate the effectiveness of a Web-based course on infection
      control accessed by physicians in training. DESIGN: Educational intervention.
      SETTING: A 607-bed urban teaching hospital. PARTICIPANTS: A total of 55
      physicians in training beginning their first postgraduate year (the iPGY1 group)
      and 59 physicians completing their first, second, or third postgraduate year (the
      oPGY group). INTERVENTION: Individuals in the iPGY1 group took a Web-based course
      on infection control practices. MEASUREMENTS: Persons in the iPGY1 group who took
      the Web-based course completed an evaluation test consisting of 15 multiple
      choice questions (total possible score, 15 points). The same test was given to
      persons in the oPGY group, who did not take the Web-based course. We compared
      scores of the Web-based test taken by subjects in the iPGY1 group immediately
      after the course with scores of the test they took 3 months after the course and
      with test scores of subjects in the oPGY group. RESULTS: The mean score (+/-SD)
      for subjects in the iPGY1 group who took the Web-based course was 10.6+/-2.2,
      compared with 8.0+/-2.5 for subjects in the oPGY group (P<.001). The mean score
      (+/-SD) for subjects in the iPGY1 group 3 months after completing the course
      decreased to 8.0+/-2.4 (P<.001 by the paired t test). For the oPGY group,
      significant differences were found between the scores (+/-SD) for subjects in the
      internal medicine (9.9+/-2.3), emergency medicine (8.4+/-1.7), pediatrics (7.0+/
      1.7), and family medicine (5.8+/-1.6) residency programs (P<.001); there were no
      significant differences in scores according to the year of residency.
      CONCLUSIONS: Web-based infection control courses are an attractive teaching tool
      for physicians in training and need to be considered for teaching infection
      control. The evaluation of information retention will help identify physicians in
      training who require further training.

PMID- 16807846
TI  - Risk factors for surgical site infection in children.
AB  - OBJECTIVES: To assess the appropriateness of using the indices developed by the
      Study on the Efficacy of Nosocomial Infection Control (SENIC) and the National
      Nosocomial Infections Surveillance (NNIS) project to determine risk factors for
      surgical site infection (SSI) in children and, if not appropriate, to explore the
      factors related to SSI in children so these factors could be used in a risk index
      for pediatric patients. DESIGN: Cohort study during more than 4 years. SETTING:
      La Paz University Hospital, a national reference center that serves Health Area 5
      of Madrid, Spain, which has approximately 500,000 inhabitants. PATIENTS:
      Convenience sample consisting of the 3,646 children admitted for surgery who had
      a postsurgical stay of more than 2 days. RESULTS: A model with 8 predictive
      factors (degree of surgical contamination; duration of surgery; type of surgery;
      use of a peripheral venous catheter, central venous catheter, or urinary
      catheter; number of diagnoses; and SSI exposition time) was created. Its relation
      to the SSI rate was better than that of the SENIC or NNIS indices. Its
      sensitivity, specificity, and area under the receiver-operating characteristic
      curve were higher than that of the SENIC index. CONCLUSIONS: The model that we
      created seems to be more adequate for predicting SSI and evaluating pediatric
      patients' intrinsic risk than the SENIC and NNIS indices.

PMID- 16807847
TI  - Control of Legionella pneumophila contamination in a respiratory hydrotherapy
      system with sulfurous spa water.
AB  - OBJECTIVE: To evaluate the effectiveness of different disinfection treatments in
      a spa water system contaminated by Legionella pneumophila and associated with a
      case of Legionella pneumonia. DESIGN: During an 18-month period, the spa water
      was analyzed by taking samples from the well, the recirculation line, and the
      final distribution devices (nebulizers and nasal irrigators). Various attempts
      were made to eradicate Legionella organisms by chemical and thermal shock. The
      final protocol consisted of heat shock treatment at 70 degrees C-75 degrees C for
      3 hours, 2 nights per week, followed by a lowering of the water temperature to 30
      deg C+/-1 deg C for use in the plant. In addition, 3 times a week superheated
      steam (at a pressure of 1 atmosphere) was introduced for 1 hour into the
      nebulization machines. SETTING: A spa at which sulfurous water was used for
      hydrotherapy by means of aerosol and nasal irrigation. PATIENT: A 74-year-old
      woman with legionnaires disease. RESULTS: After the case of infection occurred,
      L. pneumophila was isolated from the recirculation line at a concentration of
      400,000 cfu/L and from the nebulizers and nasal irrigators at levels ranging from
      3,300 to 1,800,000 cfu/L. The colonizing organisms consisted of a mixture of L.
      pneumophila serogroup 1 (12%) and serogroup 5 (88%). The shock treatment with
      chlorine dioxide and peracetic acid resulted in the eradication of Legionella
      organisms from the recirculation line but not from the water generated from the
      final distribution devices. After the restructuring of the plant and the
      application of thermal shock protocol, an evaluation after 12 months revealed no
      evidence of Legionella contamination. CONCLUSION: To prevent Legionella
      colonization, disinfection treatment is effective if associated with carefully
      selected materials, good circuit design, and good maintenance practices.

PMID- 16807848
TI  - Accuracy of healthcare worker recall and medical record review for identifying
      infectious exposures to hospitalized patients.
AB  - OBJECTIVE: To determine the validity of using healthcare worker (HCW) recall of
      patient interactions and medical record review for contact tracing in a critical
      care setting. DESIGN: Trained observers recorded the interactions of nurses,
      respiratory therapists, and service assistants with study patients in a medical
      surgical intensive care unit. These observers' records were used as the reference
      standard to test the criterion validity of using HCW recall data or medical
      record review data to identify exposure characteristics. We assessed the effects
      of previous quarantine of the HCW (because of possible exposure) and the
      availability of patients' medical records for use as memory aids on the accuracy
      of HCW recall. SETTING: A 10-bed medical-surgical intensive care unit at Mount
      Sinai Hospital in Toronto, Ontario. PATIENTS: Thirty-six HCWs observed caring for
      16 patients, for a total of 55 healthcare worker shifts. RESULTS: Recall accuracy
      was better among HCWs who were provided with patient medical records as memory
      aids (P<.01). However, HCWs tended to overestimate exposures when they used
      patient medical records as memory aids. For 6 of 26 procedures or care
      activities, this tendency to overestimate was statistically significant (P<.05).
      Most HCWs with true exposures were identified by means of this technique, despite
      the overestimations. Documentation of the activities of the 4 service assistants
      could not be found in any of the patients' medical records. Similarly, the
      interactions between 6 (19%) of 32 other patient-HCW pairs were not recorded in
      patients' medical records. CONCLUSIONS: Data collected from follow-up interviews
      with HCWs in which they are provided with patient medical records as memory aids
      should be adequate for contact tracing and for determining exposure histories.
      Neither follow-up interviews nor medical record review alone provide sufficient
      data for these purposes.

PMID- 16807849
TI  - Comparison of UV C light and chemicals for disinfection of surfaces in hospital
      isolation units.
AB  - OBJECTIVE: To determine the bactericidal effect on surfaces of ceiling- and wall
      mounted UV C (UVC) light (wavelength, 254 nm) in isolation units, compared with
      standard hospital environmental cleaning and chemical disinfection during final
      disinfection after patients are treated for infections. DESIGN: Microbial samples
      were obtained from surfaces in isolation units (patient room, anteroom, and
      bathroom) before and after irradiation with UVC, chloramine disinfection, and
      standard hospital environmental cleaning. Samples were tested using standard
      contact plates. SETTING: Four identical, negative air-pressure isolation units
      (patient room, anteroom, and bathroom) with a defined number of ceiling- and wall
      mounted UVC light units. The UVC distribution was monitored in one isolation unit
      after irradiation for approximately 40 minutes, corresponding to doses ranging
      from 160 J/m2 in a shadowed area to 19,230 J/m2 at the mostly highly exposed site
      (which is high enough to inactivate most bacterial organisms, including spores).
      RESULTS: UVC disinfection significantly reduced the number of bacteria on
      surfaces directly or indirectly exposed to UVC to a very low number, as did 5%
      chloramine disinfection alone (P<.001 for both). Completely shadowed areas in the
      isolation unit (eg, the bed rail, lockers, and mattresses) still required
      disinfection by chemicals. CONCLUSION: Disinfection with UVC light may
      significantly reduce environmental bacterial contamination and thereby protect
      the next patient housed in an isolation room. UVC disinfection may not be used
      alone but is a good addition to chemical disinfection.

PMID- 16807850
TI  - Pyrogenic reactions and hemorrhage associated with intrinsic exposure to
      endotoxin-contaminated intravenous solutions.
AB  - OBJECTIVE: An epidemiological investigation was conducted to determine risk
      factors for adverse reactions among patients in hospitals and the possibility of
      extrinsic or intrinsic contamination of intravenous solutions. DESIGN: A
      retrospective cohort study was conducted to identify solutions associated with
      adverse reactions. Implicated lots were cultured for bacteria, and endotoxin
      concentrations were measured. SETTING: Five hospitals in the state of Pernambuco,
      Brazil, were investigated from February through March 2002. PATIENTS: Surgical
      inpatients or outpatients receiving intravenous solutions during the study
      period. RESULTS: Of 355 surgical patients or outpatients treated at hospitals, 28
      (8%) developed illness within a mean of 2.5 hours after exposure to intravenous
      solutions implicated in adverse reactions; 5 (17.9%) of the case patients died.
      Laboratory testing of bottles from the lots of Ringer's lactate solution
      implicated in deaths demonstrated a high mean endotoxin concentration of 88.3
      endotoxin units (EU)/mL (range, 9.7-298.0 EU/mL), compared with the permitted
      limit in Brazil of <0.5 EU/mL. Testing of metronidazole implicated in adverse
      reactions at another hospital and produced by the same company that manufactured
      the lots Ringer's lactate solution also showed high endotoxin concentrations
      (mean level, 8.3 EU/mL [range, 5.0-58.3 EU/mL]). The outbreak was controlled
      after a national recall of the implicated brand of intravenous solutions.
      CONCLUSIONS: Case patient status was associated with use of Ringer's lactate
      solution and metronidazole from large bottles, both of which were produced by the
      same company. High endotoxin concentrations were demonstrated in unopened bottles
      of implicated products, which is consistent with intrinsic contamination. The
      high mortality rate may have been compounded by the fact that clinicians
      administered additional volumes of contaminated 0.9% isotonic sodium chloride
      solution in response to hypotension or bleeding to some surgical patients. No
      additional case patients were identified after a national recall of products,
      inspection, closure of the implicated company's manufacturing facility, and
      establishment of random quality-control testing of intravenous solutions.

PMID- 16807851
TI  - Dissemination of IMP-1 metallo- beta -lactamase-producing Acinetobacter species
      in a Brazilian teaching hospital.
AB  - OBJECTIVE: To evaluate the emergence and dissemination of metallo- beta 
      lactamase (MBL)-producing Acinetobacter species. DESIGN: All carbapenem-resistant
      Acinetobacter strains (1 strain per patient) collected during the period 1993
      2001 were evaluated. SETTING: A Brazilian tertiary care teaching hospital
      (Hospital Sao Paulo, Sao Paulo). METHODS: Seventy-three strains of carbapenem
      resistant Acinetobacter species were recovered from the organism bank of the
      hospital. All isolates were tested for antimicrobial susceptibility by broth
      microdilution methods, and the production of MBL was initially assessed by
      phenotypic tests (MBL Etest strip and a disk approximation test). The MBL enzymes
      were identified by polymerase chain reaction using primers for bla(IMP),
      bla(VIM), and bla(SPM), followed by gene sequencing. Genetic similarity among the
      carbapenem-resistant strains was evaluated by automated ribotyping. RESULTS: Only
      colistin and ampicillin-sulbactam showed reasonable in vitro activity against
      carbapenem-resistant isolates (97% and 74% of isolates susceptible,
      respectively). More than half of the isolates (55%) had a positive MBL phenotypic
      test result and a positive polymerase chain reaction result for bla(IMP-1). The
      proportion of IMP-1-producing Acinetobacter isolates among carbapenem-resistant
      strains increased from 0% in the 1993-1997 period to 29% in 1998 and 100% in the
      1999-2001 period. No carbapenem-resistant Acinetobacter isolates that harbored
      bla(VIM) or bla(SPM) were detected. Molecular typing results revealed 20
      ribogroups among carbapenem-resistant isolates. During the study period of 1994
      2001, we identified 2 major ribogroups, 52-1 (MBL-negative and MBL-positive
      strains) and 60-7 (MBL-positive strains), that had a coefficient of similarity of
      0.85 or higher. CONCLUSIONS: Our results indicate that IMP-1-producing strains of
      Acinetobacter emerged in our institution in 1998. Since then, production of this
      MBL was detected not only in the major ribogroups of carbapenem-resistant
      Acinetobacter species but also among isolates that belonged to 17 distinct
      ribogroups, indicating that this important mechanism of antimicrobial resistance
      was disseminated among distinct clones.

PMID- 16807852
TI  - Increasing antibiotic resistance among isolates of Escherichia coli recovered
      from inpatients and outpatients in a Saudi Arabian hospital.
AB  - OBJECTIVE: To study the pattern of antibiotic resistance among Escherichia coli
      and the trend in resistance during a 6-year period in a Saudi Arabian hospital.
      DESIGN: Retrospective in vitro surveillance study of the antibiotic
      susceptibility pattern among E. coli isolates recovered from outpatients and from
      inpatients. SETTING: A general hospital in Saudi Arabia. PATIENTS: All patients
      with a culture positive for E. coli during a 6-year study period. RESULTS: A
      statistically significant increase in antibiotic resistance was observed among
      outpatient and inpatient isolates of E. coli. Inpatient isolates were more likely
      to be resistant to antimicrobial agents. Among isolates from outpatients, 50%
      were resistant to ampicillin, 33% were resistant to trimethoprim-sulfamethoxazole
      (TMP-SMZ), and 14% were resistant to ciprofloxacin. Among isolates from
      inpatients, 63% were resistant to ampicillin, 44% were resistant to TMP-SMZ, and
      33% were resistant to ciprofloxacin. There was a low rate of resistance to
      imipenem (0.3% of isolates), amikacin (2%), and nitrofurantoin (2.4%-6.5%).
      Resistance to ceftazidime was detected in 9% of outpatient isolates and 17% of
      inpatient isolates. Multidrug resistance was defined as resistance to 2 or more
      classes of antibiotics. Multidrug resistance was detected in 2.0%-28.1% of
      outpatient isolates and 7.4%-39.6% of inpatient isolates, depending on the
      combination of antimicrobials tested. More isolates were resistant to ampicillin
      plus TMP-SMZ than to any other combination of antimicrobials. CONCLUSION: The
      prevalence of antibiotic resistance among outpatient and inpatient E. coli
      isolates increased during the study period. The rates of antibiotic resistance
      were statistically significantly higher among inpatient isolates, compared with
      outpatient isolates. These findings call for wiser use of antibiotics and
      continued surveillance of antibiotic resistance.

PMID- 16807853
TI  - Characteristics of programs involving canine visitation of hospitalized people in
      Ontario.
AB  - OBJECTIVES: To determine the distribution of canine-visitation programs in
      Ontario and to characterize the nature of the programs the dogs are affiliated
      with. DESIGN: A cross-sectional survey of hospitals in Ontario was used to
      determine whether they permitted dogs to visit patients and, if so, where the
      dogs originated. On the basis of this information, dog owners were then contacted
      through their respective associations and interviewed using a standardized
      questionnaire. SETTING: A cross-section of hospitals in Ontario. PARTICIPANTS: A
      total of 223 (97%) of the 231 hospitals surveyed responded. Ninety owners of 102
      visitation dogs were interviewed. RESULTS: A total of 201 (90%) of the 223
      hospitals indicated that dogs were permitted in their facilities. Origins ranged
      from national therapy-dog agencies to the patients' families. Acute care wards
      were 5.1 times as likely than other wards to disallow animals (95% confidence
      interval, 2.2-12.2; P<.001). According to the 90 dog owners included in the
      study, the screening protocols that dogs were required to pass to participate in
      their respective visitation programs were highly variable, as were the owners'
      infection control practices. Eighteen owners (20%) said they did not practice any
      infection control. Sixty-six owners (73%) allowed their dogs on patients' beds,
      and 71 (79%) let their dogs lick patients. Thirty-six owners (40%) were unable to
      name one zoonotic disease that may be transmitted from their dog. CONCLUSIONS:
      Although canine-visitation programs have become standard practice in nonacute
      human healthcare facilities, infection control and dog-screening practices are
      highly variable and potentially deficient. Hospital staff, visitation groups, pet
      owners, and veterinarians need to work together to protect both people and pets.

PMID- 16807854
TI  - Emergence of carbapenem resistance in Acinetobacter baumannii recovered from
      blood cultures in Australia.
AB  - We describe the first emergence of carbapenem-resistant Acinetobacter baumannii
      in Australia. Ninety A. baumannii isolates recovered from cultures of blood
      specimens from 69 patients were analyzed. Overall, 58 isolates (64%) were
      resistant to meropenem. The chi 2 test for linear trend revealed that emergence
      of carbapenem resistance was statistically significant during the 32-month study
      period. Selected isolates were of the same clonal type, and no genes encoding
      carbapenemases were identified.

PMID- 16807855
TI  - Dog bite transmission of antibiotic-resistant bacteria to a human.
AB  - The prevalence of multidrug-resistant bacteria in the community is increasing,
      and companion animals serve as a potential reservoir for such bacteria. This
      report describes a case of a companion dog that was treated with multiple courses
      of antibiotics for a chronic illness and transmitted multidrug-resistant bacteria
      to a human through a bite.

PMID- 16807856
TI  - Patterns in the offering of hepatitis B prophylaxis by US emergency department
      physicians.
AB  - US emergency department physicians surveyed were more likely to offer hepatitis B
      prophylaxis to patients after unknown hepatitis B status needlestick injuries
      than sexual exposures, especially consensual sex. There was no difference in
      willingness to offer prophylaxis with respect to patient occupation or age or
      with respect to ED physicians' demographic and professional characteristics.

PMID- 16807857
TI  - Pseudomonas aeruginosa sepsis in stem cell transplantation patients.
AB  - We report the epidemiological investigation of an outbreak of Pseudomonas
      aeruginosa infection in 6 patients who shared, during different periods, the same
      2 rooms of a bone marrow transplantation unit. Phenotypic and molecular analysis
      of isolates from patients and from the environment strongly suggested a single,
      environmental source of infection.

PMID- 16807858
TI  - Correlation between Legionella contamination in water and surrounding air.
AB  - We evaluated Legionella pneumophila contamination of water and surrounding air in
      a burn care department equipped with bathtubs. In water, the bacterium always
      aerosolized, but in surrounding air, it diluted itself to such a point that it
      became undetectable at 1 m or more from the source of emission, which indicated
      that patients were at low risk of inhaling a dangerous quantity of the microbe.

PMID- 16807859
TI  - Acquisition of multidrug-resistant Serratia marcescens by critically ill patients
      who consumed tap water during receipt of oral medication.
AB  - We describe an outbreak of multidrug-resistant Serratia marcescens infection and
      colonization involving adults admitted to a surgical intensive care unit.
      Examination of the outbreak revealed epidemiological evidence that consumption of
      tap water from a contaminated faucet during receipt of oral medication was the
      mechanism of S. marcescens acquisition.

PMID- 16807860
TI  - 3-Methyl-4-chlorophenol for prion decontamination of medical devices.
AB  - Disinfectants containing 3-methyl-4-chlorophenol were tested for their capacity
      to inactivate the infectious agent of scrapie. Coincubation of brain homogenates
      prepared from terminally ill scrapie-infected hamsters with the disinfectants
      rendered the prion protein PrP(Sc) sensitive to proteinase K digestion.
      Inoculation of hamsters with disinfectant-treated samples indicated a reduction
      in infectivity levels to below the limit of detection.

PMID- 16807861
TI  - Polymerase chain reaction identification of coagulase-negative Staphylococci and
      of strain diversity and spread of Staphylococcus epidermidis in a major medical
      center in Lebanon.
AB  - A 2-step polymerase chain reaction (PCR) assay and random amplification of
      polymorphic DNA (RAPD) analysis, respectively, were assessed to identify
      coagulase-negative staphylococci organisms to the species level and to determine
      the strain diversity and spread of Staphylococcus epidermidis, the most
      frequently isolated species, in a medical center in Beirut, Lebanon. Our data
      indicated that PCR was faster and was more efficient in identifying S.
      epidermidis isolates than is conventional biochemical testing. RAPD analysis have
      shown that S. epidermidis strains were scattered across the different clinical
      services, demonstrating various clusters of infection in the medical center.

PMID- 16807862
TI  - Hospital-acquired pneumonia in the intensive care units of Polish hospitals.
AB  - We analyzed the epidemiological characteristics of pneumonia in intensive care
      units of Polish hospitals. Among 11,587 patients, there were 191 cases of
      hospital-acquired pneumonia (HAP). The incidence of HAP was 5.6%, and that of
      ventilator-associated pneumonia (VAP) was 17.9%. The overall mortality rate was
      12.6%, and the mortality rate for patients who received artificial ventilation
      was 15.0%. The predominant organisms causing HAP and VAP were Pseudomonas
      aeruginosa and Escherichia coli, and 21.1% of Staphylococcus aureus isolates were
      resistant to methicillin.

PMID- 16807863
TI  - Acinetobacter nares colonization of healthy US soldiers.

PMID- 16807864
TI  - Nosocomial postsurgical meningitis in children: a 12-year survey comparing data
      from 1993-1998 with data from 1999-2004.

PMID- 16807866
TI  - [Video-electroencephalography prolonged monitoring in patients with ambulatory
      diagnosis of medically refractory temporal lobe epilepsy: application of fuzzy
      logic's model].
AB  - INTRODUCTION: The video-electroencephalography (video-EEG) prolonged monitoring
      is an important auxiliary diagnostic instrument in epilepsy, and provides
      valuable information to classify the type of crisis and epileptic syndromes and
      to localize the epileptogenic zone. The fuzzy logic gives an efficient and
      intelligent analysis method, able to make inferences over ambiguous systems, and
      has been increasing used in several areas. AIMS: To correlate clinical and
      electroencephalographic data obtained with video-EEG of patients with clinical
      and interictal electroencephalography criteria of medically refractory temporal
      lobe epilepsy (TLE) and to make inferences of diagnosis precision with the
      application of the Fuzzy Hierarchy COPPE/Cosenza Model; to investigate the
      frequency in which the clinical, syndromic and topographic diagnosis can be
      modified in these patients; to evaluate the usefulness and applicability of fuzzy
      logic on the analysis of this type of study. PATIENTS AND METHODS: Transversal,
      prospective study, that included 22 adult outpatients with ambulatory diagnosis
      of medically refractory TLE, submitted to video-EEG monitoring that varied from
      48 hours to 10 days. The grade of diagnosis precision was infered by fuzzy logic.
      RESULTS: The clinical diagnosis of epilepsy was modified in two (9%) patients,
      the syndromic in six (27.2%) and the topographic in 16 (72.7%). The fuzzy
      indicators of ambulatory diagnostic precision were: 0.91 to clinical diagnosis;
      0.74 to syndromic diagnosis and 0.36 to topographic diagnosis, considering 1 the
      maximal precision diagnostic value (attributed to the video-EEG results).
      CONCLUSIONS: The video-EEG prolonged monitoring established the clinical,
      syndromic and topographic correct diagnosis in these patients; the fuzzy logic
      best defined a mathematical value of the correspondence between ambulatorial
      diagnosis of TLE and the video-EEG prolonged monitoring.

PMID- 16807865
TI  - [A descriptive study of perinatal asphyxia and its sequelae].
AB  - INTRODUCTION: Perinatal asphyxia is a potential cause of brain injury that can
      produce some alterations on the neurologic development of the newborn. On the
      last years most part of the investigation have been focused on the
      physiopathology of the perinatal asphyxia, but correlation between asphyxia and
      brain damage is not well defined. PATIENTS AND METHODS: A retrospective study was
      made of the patients with the diagnosis of perinatal asphyxia born at the General
      Hospital of Segovia during a period of ten years (1992-2001). We took data about
      gestation, birth, neonatal period and follow-up period from their clinical
      histories. RESULTS: Over this period of ten years 703 cases of perinatal asphyxia
      have been diagnosed, supposing this an incidence of 7,2 cases of each 100
      newborns. 116 of these newborns present risk factors of brain damage and were
      followed at least two years. 53 of the 116 newborns (45%) present evidence of
      hypoxic-ischemic encephalopathy on neonatal period. During the period of two
      years, 42 of the asphyxiated infants follow up (36%) present neurologic sequelae,
      being psychomotor retardation the most common. CONCLUSION: For a correct
      interpretation of the relationship between perinatal asphyxia and neurologic
      sequelae we have to analyze all of the perinatal data and discard any other
      possible aetiology or pathogenic mechanism.

PMID- 16807867
TI  - [Evaluation of the Spanish version of the Memory Impairment Screen].
AB  - INTRODUCTION: Screening tests for detecting dementias are usually long, sometimes
      difficult to apply, and require a certain amount of instruction prior to using
      them. The Memory Impairment Screen (MIS) is a fast (3-4 minutes), easy-to-apply
      screening test that evaluates short-term verbal memory. AIM: To evaluate the
      value of the MIS for screening for dementia in our population. SUBJECTS AND
      METHODS: We evaluated 101 subjects who were divided into two groups, one
      consisting of 49 individuals with dementia according to DMS-IV criteria and the
      other made up of 52 subjects with no cognitive impairment. Demographic variables
      (sex, age, schooling) were studied together with the results from the Global
      Deterioration Scale, the Folstein Mini-Mental State Examination (MMSE), the MIS,
      the Semantic Verbal Fluency (SVF) and the Command-Condition Clock Test (CCCT).
      STATISTICAL ANALYSIS: demographic variables and the results from the tests for
      the two groups (with and without dementia) were compared, and the parameters for
      diagnostic usefulness and the areas under the ROC (aROC) were determined.
      RESULTS: No significant differences were found between the sociodemographic
      variables except for a higher mean age in the group with dementia. The MIS showed
      a sensitivity of 83.7% (95% CI: 71-97.9), which was higher than the SVF and the
      CCCT, and a specificity of 94.2% (95% CI: 84.4-98), which was higher than the
      MMSE and the SVF. The aROC of the MIS was 0.935 (95% CI: 0.954-1.006).
      CONCLUSIONS: These findings show that the MIS is a good test for screening for
      dementia, and its simplicity and quick application could make it suitable for use
      in our population.

PMID- 16807868
TI  - [Neuronal migration disorders: a cause of curable medication resistant epilepsy].
AB  - INTRODUCTION: Focal cortical dysplasia is a neuronal migration disorder that
      appears with bouts of epileptic seizures that are usually medication resistant.
      The improvements introduced into neuroimaging techniques in recent years have
      made it possible to diagnose and offer surgical treatment to certain patients who
      have been under polytherapy for many years with poor control over their seizures.
      CASE REPORT: We report the case of a 22-year-old male with epileptic fits since
      the age of 18 months, who was refractory to multiple combinations of oral
      antiepileptic drugs (AEDs) with electroencephalograms that displayed frontal,
      fast spike-wave discharges, with greater expression on the left side and findings
      from neuroimaging techniques that were repeatedly normal. After being readmitted
      to hospital because his seizures had got worse, the neuroimaging study was
      repeated and left frontal focal cortical dysplasia was observed, which led us to
      start considering neurosurgery. At present, six months after the intervention,
      the patient has had no further convulsive fits and therapy with oral AEDs is
      being reduced. CONCLUSIONS: Neuroimaging studies must be repeated in patients
      that have already been examined because in this way it may be possible to save a
      group of patients (who would otherwise have to resign to poor control over their
      seizures as well as the side effects of many AEDs) from becoming medication
      resistant.

PMID- 16807869
TI  - [The neural bases of taste aversion learning: the formation of acquired hedonic
      taste representations].
AB  - INTRODUCTION: Taste aversion conditioning is a form of associative learning in
      which certain qualities of a food (mainly its taste) are associated to specific
      negative visceral consequences that derive from eating it. Establishing this
      learning depends on gustatory-visceral integration processes carried out in the
      central nervous system. DEVELOPMENT: In this manuscript our aim is to offer a
      global view of the centres and connections that play the most significant roles
      in the formation of taste aversion learning (TAL). CONCLUSIONS: Many researchers
      consider that the initial level of integration is situated within the
      parabrachial nuclei. A priori and given the basic vital nature of TAL, its
      formation and completion could be thought to take place at this brain stem level,
      without requiring the intervention of the higher processing structures.
      Nevertheless, in the literature on TAL there is a large body of both
      neuroanatomical and neurobehavioural evidence that seems to indicate that the
      formation of TAL requires complex interactions between the parabrachial nuclei
      and certain prosencephalic structures, such as the insular cortex or the
      amygdala, among others.

PMID- 16807870
TI  - [A proposal for a clinical registry of dementias].
AB  - AIMS: We outline a proposal for the structural and functional features needed to
      develop a registry of dementias which can be used to collect standardised
      information that is both reliable and valid concerning cases of dementia in the
      specialised health care centres within a particular geographical area.
      DEVELOPMENT: Due to the shortage of information about aspects concerning the
      impact of dementias on the health care system (in terms of the usage of resources
      and patterns of detection, referral, diagnosis and treatment in usual clinical
      practice in primary and secondary care), a sequential implementation of the
      registry is proposed so that it can be adapted to each health district or region.
      The first step is to identify the cases and sources of information; second, a
      system for collecting data must be developed that allows information to be
      gathered in a standardised manner while at the same time making it possible to
      work in close collaboration with the specialists who diagnose dementia; and,
      third, it must be set up with the logistics and staff needed to centralise all
      the functions and activities of the registry. CONCLUSIONS: Epidemiological
      surveillance is an essential instrument for planning, managing and distributing
      community health resources, for following up the natural history of chronic
      diseases and for assessing the impact of programmes of prevention. In this
      respect, and from a functional point of view, the proposed registry of dementias
      meets all the basic requirements of epidemiological surveillance.

PMID- 16807871
TI  - [Update on gamma-hydroxybutyric acid].
AB  - AIMS: The article offers an updated review of the main pharmacological aspects of
      gamma-hydroxybutyric acid (GHB), as well as its clinical and behavioural effects.
      DEVELOPMENT: A number of pharmacological, neurochemical and electrophysiological
      studies have clearly shown that endogenous GHB plays a role as a neurotransmitter
      and/or neuromodulator in the central nervous system (CNS). GHB displays specific
      synthesis, release and reuptake mechanisms, as well as particular binding sites
      that suggest the existence of a central GHBergic system. This substance,
      popularly known as 'liquid ecstasy', is also a potentially abusable drug; if
      administered for prolonged periods of time it can lead to dependence and
      withdrawal symptoms after the patient stops taking it. Its chief behavioural
      actions include sedation/sleepiness, induction of absence seizures, catalepsy or
      reduced aggression, among others. Some of these effects appear to be related to
      an interaction that has been reported to exist between the GHBergic system and
      the dopaminergic and GABAergic receptors in the CNS. From the clinical point of
      view, its use has been approved in some countries to treat the narcoleptic
      syndrome, and it has also been considered for possible use in the treatment of
      alcohol or opiate abuse. Finally, recent studies conducted with laboratory
      animals suggest the existence of a possible neurotoxic effect following prolonged
      administration in abusable dosages. CONCLUSIONS: GHB is an extraordinarily
      interesting compound. It acts as a neurotransmitter/neuromodulator in the CNS. It
      is also an abusable recreational drug and may also be used to treat a number of
      different pathological conditions, the most important of which is narcolepsy. The
      possible development of neurotoxicity following prolonged administration,
      however, imposes considerable limitations on its usefulness in clinical contexts.

PMID- 16807872
TI  - [Cerebral venous thrombosis and factor V Leiden].

PMID- 16807874
TI  - [Coma induced by an overdose of intrathecal baclofen].

PMID- 16807873
TI  - [Recurring myelopathy and Sjogren's syndrome: an analysis of one case].

PMID- 16807875
TI  - Relaxing effect of ylang ylang oil on humans after transdermal absorption.
AB  - The aim of this study was to investigate the effects of ylang ylang oil (Cananga
      odorata, Annonaceae) on human physiological parameters and self-evaluation after
      transdermal absorption. Forty healthy volunteers participated in the experiments.
      Physiological parameters recorded were skin temperature, pulse rate, breathing
      rate and blood pressure. Self-evaluation was assessed by means of visual analog
      scales (VAS). The ylang ylang oil caused a significant decrease of blood pressure
      and a significant increase of skin temperature. At the behavioral level, subjects
      in the ylang ylang oil group rated themselves more calm and more relaxed than
      subjects in the control group. These findings are likely to represent a relaxing
      effect of the ylang ylang oil and provide some evidence for the usage of the
      ylang ylang oil in aromatherapy such as causing a relief of depression and stress
      in humans.

PMID- 16807876
TI  - A comparison of wound healing following treatment with Lavandula x allardii honey
      or essential oil.
AB  - The increased interest in complementary therapies has led to the investigation of
      products traditionally believed to have a beneficial effect in wound healing. Two
      such products are honey and lavender essential oil. In this study a rat
      excisional wound model was used to investigate the action of Lavandula x allardii
      honey and essential oil, and a standard therapeutic honey (Medihoney). Four 8 mm
      wounds were created surgically on the dorsal surface of each rat and honey or
      essential oil applied to the wounds twice a day for 4 days. Wound healing was
      analysed by wound contraction and capillary volume at 5 and 12 days post-surgery.
      Although no statistically significant difference in wound contraction was
      observed for the essential oil or honey treated wounds relative to the untreated
      control, both honeys were shown to reduce the capillary volume in the wound site
      at day 12 with no difference between the honeys (control 154 +/- 14 microm(3) vs
      L. x allardii honey 77 +/- 18 microm(3) and Medihoney 89 +/- 39 microm(3), p <
      0.001; mean +/- SD). This suggests that scar maturation in these animals was more
      advanced than in other groups. These data suggest that L. x allardii honey, but
      not essential oil, has a beneficial action in wound healing.

PMID- 16807878
TI  - Effects of ephedrae herba on melanogenesis and gene expression profiles using
      cDNA microarray in B16 melanocytes.
AB  - Ephedrae Herba (EH) is obtained by drying the stems of Ephedra sinica Stapf
      (family Ephedraceae). EH has been used clinically to treat colds and to reduce
      edema in skin. The effects of EH on melanogenesis were studied in B16 murine
      melanocytes. The tyrosinase activity and melanin content were measured after
      incubation with EH. Both reverse transcription-polymerase chain reaction and cDNA
      microarray analysis were used to study the mechanism of EH action. EH decreased
      tyrosinase activity and melanin content in a dose-dependent manner. EH decreased
      microphthalmia-associated transcription factor (MITF) and tyrosinase gene
      expression. These effects were controlled by MITF-mediated regulation of
      tyrosinase gene expression. EH also altered the expression of about 100 other
      genes. These results suggest that EH may be used clinically to treat freckles and
      liver spots.

PMID- 16807877
TI  - Pretreatment with neem (Azadirachta indica) leaf preparation in Swiss mice
      diminishes leukopenia and enhances the antitumor activity of cyclophosphamide.
AB  - Cancer chemotherapy is associated with several life threatening complications,
      including bone marrow suppression and leucopenia. To overcome this problem,
      colony stimulating factor (CSF), granulocyte colony stimulating factor (GCSF) and
      granulocyte macrophage colony stimulating factor (GMCSF), can be used, however,
      these therapeutics are expensive and have several disadvantages, including tumor
      growth promoting activities. This study attempted to use an immunostimulatory
      neem (Azadirachta indica) leaf preparation (NLP) to prevent the cyclophosphamide
      (CYP) induced reduction in the WBC count. Pretreatment of mice with NLP reduced
      the extent of leucopenia and neutropenia in normal and tumor bearing CYP treated
      mice. NLP pretreatment enhanced in vitro tumor cell cytotoxicity by peripheral
      blood mononuclear cells (PBMC) from CYP treated mice in either normal or tumor
      bearing conditions. Similarly, NLP pretreatment of mice enhanced the CYP mediated
      in vivo tumor growth inhibition and survivability of the host. Based on these
      observations, it is concluded that NLP would be an effective tool to reduce CYP
      induced hematological complications.

PMID- 16807879
TI  - Inhibition of nitric oxide synthase expression in activated microglia and
      peroxynitrite scavenging activity by Opuntia ficus indica var. saboten.
AB  - Activated microglia by neuronal injury or inflammatory stimulation overproduce
      nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen
      species (ROS) such as superoxide anion, resulting in neurodegenerative diseases.
      The toxic peroxynitrite (ONOO-), the reaction product of NO and superoxide anion
      further contributes to oxidative neurotoxicity. A butanol fraction obtained from
      50% ethanol extracts of Opuntia ficus indica var. saboten (Cactaceae) stem (SK
      OFB901) and its hydrolysis product (SK OFB901H) inhibited the production of NO in
      LPS-activated microglia in a dose dependent manner (IC50 15.9, 4.2 microg/mL,
      respectively). They also suppressed the expression of protein and mRNA of iNOS in
      LPS-activated microglial cells at higher than 30 microg/mL as observed by western
      blot analysis and RT-PCR experiment. They also inhibited the degradation of I
      kappaB-alpha in activated microglia. Moreover, they showed strong activity of
      peroxynitrite scavenging in a cell free bioassay system. These results imply that
      Opuntia ficus indica may have neuroprotective activity through the inhibition of
      NO production by activated microglial cells and peroxynitrite scavenging
      activity.

PMID- 16807880
TI  - The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra
      on CD69 expression and immune cell activation in humans.
AB  - The increasing use of medicinal herbs among the general public has piqued the
      need for scientific-based research to determine the mechanism of action of herbs
      administered orally in human subjects. The ability of three herbs, Echinacea
      purpurea, Astragalus membranaceus and Glycyrrhiza glabra, to activate immune
      cells in human subjects was assessed in this pilot study. The effect of these
      herbs when ingested for 7 days was measured both when administered singly, and in
      combination, using flow cytometry. The primary cell activation marker measured
      was CD69. The results demonstrate that Echinacea, Astragalus and Glycyrrhiza
      herbal tinctures stimulated immune cells as quantified by CD69 expression on CD4
      and CD8 T cells. This activation took place within 24 h of ingestion, and
      continued for at least 7 days. In addition, these three herbs had an additive
      effect on CD69 expression when used in combination.

PMID- 16807881
TI  - Effects of Papaver rhoeas extract on the acquisition and expression of morphine
      induced behavioral sensitization in mice.
AB  - In the present study, the effects of a water-alcohol extract of Papaver rhoeas on
      the acquisition and expression of morphine-induced behavioral sensitization in
      mice were investigated. The subcutaneous (s.c.) administration of morphine (50
      mg/kg) induced locomotor activity in animals, whereas the drug did not show an
      effect at a dose of 5 mg/kg. On the other hand, intraperitoneal (i.p.)
      administration of the plant extract (25, 50 and 100 mg/kg) did not show any
      effect. The locomotor behavioral response was enhanced in mice pretreated with
      morphine (5 mg/kg, daily x 3 days) alone, indicating that sensitization had
      developed. Extract (25, 50 and 100 mg/kg, i.p.) administration, 30 min before
      each of the three daily doses of morphine decreased the development of
      sensitization. Moreover, intraperitoneal administration of the plant extract (25,
      50 and 100 mg/kg) 30 min before the test reduced the expression of morphine
      induced behavioral sensitization. The results indicate that administration of the
      extract of Papaver rhoeas reduced the acquisition and expression of morphine
      induced behavioral sensitization in mice.

PMID- 16807882
TI  - Glycosides derived from Hemidesmus indicus R. Br. root inhibit adherence of
      Salmonella typhimurium to host cells: receptor mimicry.
AB  - For centuries, indigenous plants have been used against enteritis but their
      molecular targets and mode of action remain obscure. The present study was
      carried out to elucidate the protective and therapeutic role, if any, of
      glycosides from Hemidesmus indicus against S. typhimurium-induced pathogenesis.
      Studies were carried out in a human intestinal cell line (Int 407) and a murine
      macrophage cell line (P388D1) in order to evaluate its potency in local as well
      as systemic infections. The inhibitory role of the glycosides present in
      Hemidesmus indicus root extract (GHI) were tested by pre-coating the cells (both
      Int 407 and P388D1) with GHI prior to infection, and by neutralizing the wild
      type bacteria with GHI before cell infection. In both cases, GHI protected the
      host cells from the cytotoxic effects of the wild S. typhimurium. This suggests
      that the biologically significant sugars (hexose, hexosamine, fucose and sialic
      acid etc) present in GHI might be mimicking host cell receptor saccharides and
      thereby blocking the bacterial ligands from binding to the host cells. Int 407
      cells infected with wild-type bacteria had a diffused adherence pattern after 4 h
      incubation, but this typical character was not observed in cells infected with
      GHI-treated bacteria and the cells were normal in appearance at 4 h. After 18 h
      cells infected with wild-type bacteria were hypertrophoid with a disintegrated
      membrane and wrapped in a bacterial coat, whereas cells infected with treated
      bacteria had comparatively less morphological changes and few defective shrunken
      rods adhered locally. This suggests that the glycosides can change the adherence
      pattern of S. typhimurium from diffused to local. Treated bacteria had less
      adherence and invasion capability in Int 407 as well as P388D1 cells. The results
      show the decreased ability of adherence of GHI-treated S. typhimurium was due to
      a loss of surface hydrophobicity. A nonspecific binding between S. typhimurium
      and the glycosides was confirmed using ELISA. In summary, the glycosides of H.
      indicus root inhibited S. typhimurium induced pathogenesis nonspecifically, by
      reducing bacterial surface hydrophobicity and perhaps also by mimicking host cell
      receptors, thereby blocking its attachment to host cell and further pathological
      effects.

PMID- 16807883
TI  - Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of
      Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats.
AB  - The present study was undertaken to investigate the analgesic, antiinflammatory
      and hypoglycaemic effects of Zingiber officinale dried rhizomes ethanol extract
      (ZOE) in mice and rats. The analgesic effect of ZOE was evaluated by 'hot-plate'
      and 'acetic acid' analgesic test methods in mice; while the antiinflammatory and
      hypoglycaemic effects of the plant extract were investigated in rats, using fresh
      egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes
      mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and
      chlorpropamide (250 mg/kg) were used as reference drugs for comparison. ZOE (50
      800 mg/kg i.p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic
      effects against thermally and chemically induced nociceptive pain in mice. The
      plant extract (ZOE, 50-800 mg/kg p.o.) also significantly (p < 0.05-0.001)
      inhibited fresh egg albumin-induced acute inflammation, and caused dose-related,
      significant (p < 0.05-0.001) hypoglycaemia in normal (normoglycaemic) and
      diabetic rats. The findings of this experimental animal study indicate that
      Zingiber officinale rhizomes ethanol extract possesses analgesic,
      antiinflammatory and hypoglycaemic properties; and thus lend pharmacological
      support to folkloric, ethnomedical uses of ginger in the treatment and/or
      management of painful, arthritic inflammatory conditions, as well as in the
      management and/or control of type 2 diabetes mellitus in some rural Africa
      communities.

PMID- 16807884
TI  - In Vitro antioxidative activity of pumpkin seed (Cucurbita pepo) protein isolate
      and its In Vivo effect on alanine transaminase and aspartate transaminase in
      acetaminophen-induced liver injury in low protein fed rats.
AB  - The antioxidative effects of pumpkin seed protein isolate (Cucurbita pepo) were
      investigated in vitro. The isolate exhibited about 80% radical scavenging
      activity, chelating activity of approximately 64% on Fe2+ ions and an inhibition
      of approximately 10% of xanthine oxidase. Subsequently the effects of the isolate
      on the plasma activity levels of alanine transaminase and aspartate transaminase
      against acetaminophen induced acute liver injury in low-protein fed male Sprague
      Dawley rats were ascertained. The rats were maintained on a low-protein diet for
      5 days and divided into three subgroups. Two subgroups were injected with
      acetaminophen and the other with an equivalent amount of polyethylene glycol 400.
      Two hours after intoxication one of the two subgroups was administered with the
      protein isolate. Rats from the different subgroups were killed at 24, 48 and 72 h
      after treatment. After 5 days on the low-protein diet the activity levels of the
      enzymes were significantly higher than their counterparts on a normal balanced
      diet. The administration of protein isolate after acetaminophen intoxication
      resulted in significantly reduced activity levels. It is concluded that the
      protein isolate has promising antioxidative properties. Furthermore, the isolate
      administration was effective in alleviating the detrimental effects associated
      with protein malnutrition and acetaminophen intoxication.

PMID- 16807885
TI  - Extract of Coptidis rhizoma induces cytochrome-c dependent apoptosis in
      immortalized and malignant human oral keratinocytes.
AB  - Coptidis rhizoma (C. rhizoma) had been demonstrated as an antioxidant and
      anticancer agent, however, its antioral cancer mechanism still remains unclear.
      Using water extracts of C. rhizoma, growth and apoptosis-related experiments for
      the treatment of multi-stage of oral cancer were carried out on immortalized
      human oral keratinocytes (IHOK), primary oral cancer cells (HN4), metastatic oral
      cancer cells (HN12) and human skin keratinocytes (HaCaT) by MTT assay, three
      dimensional (3-D) raft cultures, western blotting, cell cycle analysis, nuclear
      staining and cytochrome c expression related to the apoptosis signaling pathway.
      C. rhizoma inhibited the proliferation of immortalized and malignant oral
      keratinocytes in a dose- and time-dependent manner. In 3-D organotypic culture,
      C. rhizoma-treated cells showed less maturation than the control cells,
      displaying low surface keratinization and decreased epithelial thickness. The
      major mechanism of growth inhibition by C. rhizoma appears to be the induction of
      apoptosis, which is supported by the results of the cell cycle analysis, FITC
      annexin V staining, DNA fragmentation assay and DAPI staining. The induction of
      apoptosis by C. rhizoma was more prominent in immortalized keratinocytes than in
      malignant oral keratinocytes. Cytochrome-c release from mitochondria, accompanied
      by the activation of caspase-3, was observed in C. rhizoma-treated IHOK and oral
      cancer cells. These results suggest that C. rhizoma has apoptotic effects in
      immortalized and malignant oral keratinocytes via the mitochondrial signaling
      pathway.

PMID- 16807886
TI  - Artificial extracellular matrix proteins contain heparin-binding and RGD
      containing domains to improve osteoblast-like cell attachment and growth.
AB  - Through the recombinant DNA technology, it is possible to create artificial
      extracellular matrix (aECM) proteins with domains chosen to modulate cellular
      behaviors. In this study, we constructed three aECM proteins containing both
      heparin-binding and RGD-containing domains (387RGDS, Tri-FN10, and TNC-FN3)
      produced in Escherichia coli. Promotion of MG-63 cell attachment and growth in
      two-dimensional (2D) cultures (tissue culture plate, polycaprolactone membrane)
      and 3D cultures (Cytodex 1 and Plastic Plus microcarriers) were demonstrated on
      these three aECM protein-coated surfaces. These three aECM proteins improved MG
      63 cell attachment and growth in the order TNC-FN3 > Tri-FN10 > 387RGDS in both
      2D and 3D cultures. This study is the first report of the construction of aECM
      proteins that contain both heparin-binding and RGD-containing domains used in
      osteoblast tissue engineering applications.

PMID- 16807887
TI  - Multi-template approach to modeling engineered disulfide bonds.
AB  - The key issue for disulfide bond engineering is to select the most appropriate
      location in the protein. By surveying the structure of experimentally engineered
      disulfide bonds, we found about half of them that have geometry incompatible with
      any native disulfide bond geometry. To improve the current prediction methods
      that tend to apply either ideal geometrical or energetical criteria to single
      three-dimensional structures, we have combined a novel computational protocol
      with the usage of multiple protein structures to take into account protein
      backbone flexibility. The multiple structures can be selected from either
      independently determined crystal structures for identical proteins, models of
      nuclear magnetic resonance experiments, or crystal structures of homology-related
      proteins. We have validated our approach by comparing the predictions with known
      disulfide bonds. The accuracy of prediction for native disulfide bonds reaches
      99.6%. In a more stringent test on the reported engineered disulfide bonds, we
      have obtained a success rate of 93%. Our protocol also determines the oxido
      reduction state of a predicted disulfide bond and the corresponding mutational
      cost. From the energy ranking, the user can easily choose top predicted sites for
      mutagenesis experiments. Our method provides information about local stability of
      the engineered disulfide bond surroundings.

PMID- 16807888
TI  - Trout Ea4- or human Eb-peptide of pro-IGF-I disrupts heart, red blood cell, and
      vasculature development in zebrafish embryos.
AB  - E-peptide of the pro-insulin-like growth factor (pro-IGF)-I is produced by
      proteolytic cleavage of the pro-hormone in post-translational processing.
      Introduction of a transgene encoding a secreted form of rtEa4- or hEb-peptide
      into newly fertilized zebrafish (Danio rerio) eggs by electroporation or
      microinjection resulted in embryos with abnormal cardiovascular features and
      reduced red blood cells and vasculature. Two different phenocopies of heart
      developmental defects were observed: (i) Group I embryos exhibited heart
      development arrested at the heart muscle stage and (ii) group II embryos
      exhibited heart development arrested at the heart tube stage. Both groups of
      embryos also exhibited reduction of red blood cells and vasculature. The mRNA
      levels of genes essential for heart development (GATA 5 and NKX2.5),
      hematopoiesis (GATA 1 and GATA 2), and vasculogenesis (VEGF) in normal and
      defective embryos were determined by quantitative real-time RT-PCR at 36 hr post
      fertilization (hpf). Significant reduction of GATA 5, NKX2.5, GATA 1, GATA 2, and
      VEGF mRNA levels was observed in both groups of defective embryos. These results
      suggest that overexpression of rtEa4 or hEb transgene in zebrafish embryos
      disrupts heart development, hematopoiesis, and vasculogenesis by reducing the
      levels of GATA 5, NKX2.5, GATA 1, GATA 2, and VEGF mRNA.

PMID- 16807889
TI  - Astrocytes and developmental white matter disorders.
AB  - There is an increasing awareness that the astrocytes in the immature
      periventricular white matter are vulnerable to ischemia and respond to
      inflammation. Here we provide a synopsis of the articles that have evaluated the
      causes and consequences of developmental brain injuries to white matter
      astrocytes as well as the consequences of several genetic mutations that result
      in abnormal astrocyte development. Emerging data suggest that the astrocytes are
      not simply responding to the injury but are likely victims as well as culprits.
      Given the important roles that astrocytes play in maintaining ionic,
      neurotransmitter, and metabolic homeostasis in the brain, a more thorough
      understanding of the mechanisms that lead to their incapacitation, demise, or
      reactions as well as a better understanding of the stimuli that regulate their
      neuroprotective and regenerative properties will enable these cells to be
      manipulated to preserve the integrity of white matter and to potentially provide
      therapeutics to enhance neonatal regeneration and recovery from brain injury.

PMID- 16807890
TI  - Microglia and inflammation: impact on developmental brain injuries.
AB  - Inflammation during the perinatal period has become a recognized risk factor for
      developmental brain injuries over the past decade or more. To fully understand
      the relationship between inflammation and brain development, a comprehensive
      knowledge about the immune system within the brain is essential. Microglia are
      resident immune cells within the central nervous system and play a critical role
      in the development of an inflammatory response within the brain. Microglia are
      critically involved with both the innate and adaptive immune system, regulating
      inflammation and cell damage within the brain via activation of Toll-like
      receptors, production of cytokines, and a myriad of other intracellular and
      intercellular processes. In this article, microglial physiology is reviewed along
      with the role of microglia in developmental brain injuries in humans and animal
      models. Last, microglial functions within the innate and adaptive immune system
      will be summarized. Understanding the processes of inflammation and microglial
      activation is critical for formulating effective preventative and therapeutic
      strategies for developmental brain injuries.

PMID- 16807891
TI  - Determination of eugenol in rat plasma by liquid chromatography-quadrupole ion
      trap mass spectrometry using a simple off-line dansyl chloride derivatization
      reaction to enhance signal intensity.
AB  - A rapid, selective and sensitive method was developed for the determination of
      eugenol concentration using an off-line dansyl chloride derivatization step to
      enhance signal intensity. The method consisted of a protein precipitation
      extraction followed by derivatization with dansyl chloride and analysis by full
      scan liquid chromatography electrospray quadrupole ion trap mass spectrometry (LC
      ESI-QIT). The separation was achieved using a 100 x 2 mm C(8) analytical column
      combined with an isocratic mobile phase composed of 75:25 acetonitrile: 0.1%
      formic acid in water set at a flow rate of 0.25 mL/min. Signal intensity of the
      eugenol-dansyl chloride derivative was increased up to 100-fold as compared with
      the underivatized eugenol in positive electrospray mode. An analytical range of
      100-20,000 ng/mL was used in the calibration curve of plasma and blood samples.
      The LOD observed was 0.5 pg injected on column. The novel method met all
      requirements of specificity, sensitivity, linearity, precision, accuracy and
      stability. In conclusion, a rapid and sensitive LC-ESI/MS/MS method using a
      derivatization agent was developed to enhance signal intensity of eugenol.

PMID- 16807892
TI  - Prediction of upper aerodigestive tract cancer by slide-based cytometry.
AB  - AIM: To evaluate slide-based cytometry in screening for and following up of
      carcinoma of the upper aerodigestive tract using swabs for a minimal-invasive
      approach. METHODS: Laser scanning cytometry (LSC) was used for multiparametric
      analysis of cells stained for cytokeratin and DNA to determine the DNA-index (DI)
      of the tumor cells. Histograms with 0.95 < DI < 1.05 and 1.9 < DI < 2.1 were
      defined as DNA euploid and any other DI as DNA aneuploid. After subsequent HE
      staining, single cells were relocalized in order to document morphology.
      Conventional cytology was also performed on a subset of the slides. Routine
      histopathology of parallel biopsies served as gold standard in all cases.
      RESULTS: 115 swabs from 109 patients were obtained from the entire upper
      aerodigestive tract. 16 swabs were classified as insufficient for LSC. In the
      remaining 99 specimens, 1 benign lesion was misclassified as malignant, while 61
      of the 75 malignant lesions were correctly identified. This corresponds to
      predictive values of 98.4% and 62.2% for the detection of malignant and benign
      samples by LSC. CONCLUSION: This pilot study demonstrates the validity of LSC
      screening for the identification of tumor malignancy in the upper aerodigestive
      tract from swab collected cytological material.

PMID- 16807893
TI  - Scanning cytometry with a LEAP: laser-enabled analysis and processing of live
      cells in situ.
AB  - BACKGROUND: Scanning cytometry now has many of the features (and power) of
      multiparameter flow cytometry while keeping its own advantages as an imaging
      technology. Modern instruments combine capabilities of scanning cytometry with
      the ability to manipulate cells. A new technology, called LEAP (laser-enabled
      analysis and processing), offers a unique combination of capabilities in cell
      purification and selective macromolecule delivery (optoinjection). METHODS: LEAP
      mediated cell purification and optoinjection effects were assessed in model
      experiments using adherent and suspension cell types and cell mixtures plated and
      processed at different densities. Optoinjection effects were visualized by
      delivering fluorescent dextrans into cells. Results were analyzed using the LEAP
      instrument's own imaging system as well as by fluorescence and confocal
      microscopy. RESULTS: Live cell samples (adherent and suspension) could be
      purified to 90-100% purity with 50-90% yield, causing minimal cell damage
      depending on the cell type and plating density. Nearly one hundred percent of the
      targeted cells of all cell types examined could be successfully optoinjected with
      dextrans of 3-70 kDa, causing no visual damage to the cells. Indirect
      optoinjection effects were observed on untargeted cells within 5-60 microm to
      targeted areas under conditions used here. CONCLUSIONS: LEAP provides solutions
      in cell purification and targeted macromolecule delivery for traditional and
      challenging applications where other methods fall short.

PMID- 16807894
TI  - Slide-based cytometry for cytomics--a minireview.
AB  - In the postgenomic era, to gain the most detailed quantitative data from
      biological specimens has become increasingly important in the emerging new fields
      of high-content and high-throughput single-cell analysis for systems biology and
      cytomics. Areas of research and diagnosis with the demand to virtually measure
      "anything" in the cell include immunophenotyping, rare cell detection and
      characterization in the case of stem cells and residual tumor cells, tissue
      analysis, and drug discovery. Systemic analysis is also a prerequisite for
      predictive medicine by genomics, proteomics, and cytomics. This issue of
      Cytometry Part A is dedicated to innovative concepts of system wide single cells
      analysis and manipulation, new technologies, data analysis and display, and,
      finally, quality assessment. The manuscripts to these chapters are provided by
      cutting edge experts in the fields. This overview will briefly highlight the most
      important aspects of this continuously developing field.

PMID- 16807895
TI  - Toward complete laser ablation of melanoma contaminant cells in a co-culture
      outgrowth model via image cytometry.
AB  - BACKGROUND: Contaminant cancer cells in autologous transplant tissue can cause
      relapse and the rates are unknown. A method capable of removing all contaminant
      cells with a high probability detected by cytomic analyses would be useful.
      Neither 100% cell purging nor techniques for measuring the probability of success
      have been developed. Here, we report a method for removing 100% of the cells
      under ideal staining conditions and quantify the probability of success. METHODS:
      Laser ablation was combined with previously reported automated microscopy to
      purge contaminant cells and evaluate 100% ablation in a co-culture model of
      prestained mouse melanoma cells mixed with mouse NIH-3T3 cells. Melanoma passage
      efficiency was measured by: (1) micropipetting single cells into microtiter wells
      and (2) ablating all but one melanoma cell in co-cultures. RESULTS: (74 +/- 5)%
      of single melanoma cells pipetted into microtiter plate wells divided at least
      once. With ablation of all but one contaminant cell in co-cultures, melanoma
      dominated in (62 +/- 8)% cultures in 21 days. With 100% ablation in six
      additional experiments, no melanoma outgrowth was observed, giving a >99.1%
      probability that all contaminant melanoma cells were purged. CONCLUSIONS: We
      successfully demonstrated a model for complete ablation within a defined
      probability using automated high-content image cytometry with ideal staining
      conditions. The results show that the instrumentation is capable of delivering
      100% ablation at a defined probability and establishes the basis for further
      studies with clinical models wherein pretherapeutic cytomic analyses of unique
      cellular expression and/or morphological characteristics will be key for
      contaminant cancer cell identification.

PMID- 16807896
TI  - Individual cell-based models of the spatial-temporal organization of
      multicellular systems--achievements and limitations.
AB  - Computational approaches of multicellular assemblies have reached a stage where
      they may contribute to unveil the processes that underlie the organization of
      tissues and multicellular aggregates. In this article, we briefly review and
      present some new results on a number of 3D lattice free individual cell-based
      mathematical models of epithelial cell populations. The models we consider here
      are parameterized by bio-physical and cell-biological quantities on the level of
      an individual cell. Eventually, they aim at predicting the dynamics of the
      biological processes on the tissue level. We focus on a number of systems, the
      growth of cell populations in vitro, and the spatial-temporal organization of
      regenerative tissues. For selected examples we compare different model approaches
      and show that the qualitative results are robust with respect to many model
      details. Hence, for the qualitative features and largely for the quantitative
      features many model details do not matter as long as characteristic biological
      features and mechanisms are correctly represented. For a quantitative prediction,
      the control of the bio-physical and cell-biological parameters on the molecular
      scale has to be known. At this point, slide-based cytometry may contribute. It
      permits to track the fate of cells and other tissue subunits in time and
      validated the organization processes predicted by the mathematical models.

PMID- 16807897
TI  - Quality assessment of confocal microscopy slide based systems: performance.
AB  - BACKGROUND: All fluorescence slide-based cytometry detections systems basically
      include the following components: (1) an excitation light source, (2)
      intermediate optics, and (3) a detection device consisting of a CCD camera or a
      PMT. The optical principles employed is slide-based systems are similar to those
      of confocal microscopes (CLSM). METHODS: The following tests evaluated confocal
      equipment performance: dichroic reflectivity, field illumination, lens
      performance, laser power output, spectral registration, axial resolution, PMT
      reliability, and system noise. RESULTS: Quality assurance tests provide a basis
      to determine if the equipment is operating correctly. Laser power, PMTs function,
      dichroic reflection, spectral registration, axial registration, system noise and
      sensitivity, lens performance and laser stability were tested colocalization of
      UV and visible peaks of a bead should be less than 210 nm. Interference contrast
      optics decrease fluorescence resolution. CONCLUSIONS: QA tests that assess CLSM
      system performance are also applicable to other slide-based systems. By
      utilization this type of testing approach, the subjective nature of assessing the
      CLSM may be eliminated. These tests serve as guidelines for other investigators
      to ensure that their machines are providing data that is accurate with the
      necessary resolution, sensitivity and precision.

PMID- 16807898
TI  - Quality assessment of confocal microscopy slide-based systems: instability.
AB  - BACKGROUND: All slide-based fluorescence cytometry detections systems basically
      include an excitation light source, intermediate optics, and a detection device
      (CCD or PMT). Occasionally, this equipment becomes unstable, generating
      unreliable and inferior data. METHODS: A number of tests have been devised to
      evaluate equipment performance and instability. The following four instability
      tests are described: galvanometer scanning, stage drift, correct wavelength
      spectral detection, and long-term laser power. RESULTS: Quality assurance tests
      revealed that a confocal microscope can become unstable in the following
      parameters, yielding inaccurate data: laser power, PMTs functionality,
      spectrophotometer accuracy, galvanometer scanning and laser stability, and stage
      drift. Long-term laser power stability has been observed to vary greatly.
      CONCLUSIONS: Confocal systems can become unstable in the following parameters:
      long-term laser power, galvanometer scanning, spectrophotometer accuracy, and
      stage stability. Instability in any of these parameters will affect image
      quality. Laser power fluctuations result from either a defective Acousto-optic
      tunable filter or improper heat dissipation. Spectrophotometer instability will
      generate unreliable spectra data, extra light reflections, and poor image
      quality. Galvanometer scanning instability yields poor image quality while
      microscope stage drift results in a sample going out of the plane of focus. With
      minor modifications, these tests may be applicable to other slide-based systems.

PMID- 16807899
TI  - Characterization of human monocyte-derived microglia-like cells.
AB  - Microglial cells are central to brain immunity and intervene in many human
      neurological diseases. The aim of this study was to develop a convenient cellular
      model for human microglial cells, suitable for HIV studies. Microglia derive from
      the hematogenous myelomonocytic lineage, possibly as a distinct subpopulation but
      in any case able to invade the CNS, proliferate, and differentiate into ameboid
      and then ramified microglia in the adult life. We thus attempted to derive
      microglia-like cells from human monocytes. When cultured with astrocyte
      conditioned medium (ACM), monocytes acquired a ramified morphology, typical of
      microglia. They overexpressed substance P and the calcium binding protein Iba-1
      and dimly expressed class II MHC, three characteristics of microglial cells.
      Moreover, they also expressed a potassium inward rectifier current, another
      microglia-specific feature. These monocyte-derived microglia-like cells (MDMi)
      were CD4(+)/CD14(+), evocative of an activated microglia phenotype. When treated
      with lipopolysaccharide (LPS), MDMi lost their overexpression of substance P,
      which returned to untreated monocyte-derived macrophage (MDM) level. Compared
      with MDM, MDMi expressed higher CD4 but lower CCR5 levels; they could be infected
      by HIV-1(BaL), but produced less virus progeny than MDM did. This model of human
      microglia may be an interesting alternative to primary microglia for large scale
      in vitro HIV studies and may help to better understand HIV-associated
      microgliosis and chronic inflammation in the brain.

PMID- 16807900
TI  - Synaptophysin protein and mRNA expression in the human hippocampal formation from
      birth to old age.
AB  - In the human neocortex, progressive synaptogenesis in early postnatal life is
      followed by a decline in synaptic density, then stability from adolescence until
      middle age. No comparable data are available in the hippocampus. In this study,
      the integral synaptic vesicle protein synaptophysin, measured
      immunoautoradiographically, was used as an index of synaptic terminal abundance
      in the hippocampal formation of 37 subjects from 5 weeks to 86 yr old, divided
      into 4 age groups (10 infants, 15 adolescents/young adults, 6 adults, and 6
      elderly). In all hippocampal subfields, synaptophysin was lowest in infancy, but
      did not differ significantly between the older age groups, except in dentate
      gyrus (DG) where the rise was delayed until adulthood. A similar developmental
      profile was found in the rat hippocampus. We also measured synaptophysin mRNA in
      the human subjects and found no age-related changes, except in parahippocampal
      gyrus wherein the mRNA declined from infancy to adolescence, and again in old
      age. The synaptophysin protein data demonstrate a significant presynaptic
      component to human postnatal hippocampal development. In so far as synaptophysin
      abundance reflects synaptic density, the findings support an increase in
      hippocampal and parahippocampal synapse formation during early childhood, but
      provide no evidence for adolescent synaptic pruning. The mRNA data indicate that
      the maturational increases in synaptophysin protein are either translational
      rather than transcriptional in origin, or else are secondary to mRNA increases in
      neurons, the cell bodies of which lie outside the hippocampal formation.

PMID- 16807901
TI  - Influence of point mutations on the flexibility of cytochrome b5: molecular
      dynamics simulations of holoproteins.
AB  - Two membrane-bound isoforms of cytochrome b5 have been identified in mammals, one
      associated with the outer mitochondrial membrane (OM b5) and the other with the
      endoplasmic reticulum (microsomal, or Mc b5). The soluble heme binding domains of
      OM and Mc b5 have highly similar three-dimensional structures but differ
      significantly in physical properties, with OM b5 exhibiting higher stability due
      to stronger heme association. In this study, we present results of 8.5-ns length
      molecular dynamics simulations for rat Mc b5, bovine Mc b5, and rat OM b5, as
      well as for two rat OM b5 mutants that were anticipated to exhibit properties
      intermediate between those of rat OM b5 and the two Mc proteins: the
      A18S/I32L/L47R triple mutant (OM3M) and the A18S/I25L/I32L/L47R/L71S quintuple
      mutant (OM5M). Analysis of the structure, fluctuations, and interactions showed
      that the five b5 variants used in this study differed in organization of their
      molecular surfaces and heme binding cores in a way that could be used to explain
      certain experimentally observed physical differences. Overall, our simulations
      provided qualitative microscopic explanations of many of the differences in
      physical properties between OM and Mc b5 and two mutants in terms of localized
      changes in structure and flexibility. They also reveal that opening of a surface
      cleft between hydrophobic cores 1 and 2 in bovine Mc b5, observed in two
      previously reported simulations (E. M. Storch and V. Daggett, Biochemistry, 1995,
      Vol. 34, pp. 9682-9693; A. Altuve, Biochemistry, 2001, Vol. 40, pp. 9469-9483),
      probably resulted from removal of crystal contacts and likely does not occur on
      the nanosecond time scale. Finally, the MD simulations of OM5M b5 verify that
      stability and dynamic properties of cytochrome b5 are remarkably resistant to
      mutations that dramatically alter the stability and structure of the apoprotein.

PMID- 16807902
TI  - Assembly of transmembrane helices of simple polytopic membrane proteins from
      sequence conservation patterns.
AB  - The transmembrane (TM) domains of most membrane proteins consist of helix
      bundles. The seemingly simple task of TM helix bundle assembly has turned out to
      be extremely difficult. This is true even for simple TM helix bundle proteins,
      i.e., those that have the simple form of compact TM helix bundles. Herein, we
      present a computational method that is capable of generating native-like
      structural models for simple TM helix bundle proteins having modest numbers of TM
      helices based on sequence conservation patterns. Thus, the only requirement for
      our method is the presence of more than 30 homologous sequences for an accurate
      extraction of sequence conservation patterns. The prediction method first
      computes a number of representative well-packed conformations for each pair of
      contacting TM helices, and then a library of tertiary folds is generated by
      overlaying overlapping TM helices of the representative conformations. This
      library is scored using sequence conservation patterns, and a subsequent
      clustering analysis yields five final models. Assuming that neighboring TM
      helices in the sequence contact each other (but not that TM helices A and G
      contact each other), the method produced structural models of Calpha atom root
      mean-square deviation (CA RMSD) of 3-5 A from corresponding crystal structures
      for bacteriorhodopsin, halorhodopsin, sensory rhodopsin II, and rhodopsin. In
      blind predictions, this type of contact knowledge is not available. Mimicking
      this, predictions were made for the rotor of the V-type Na(+)-adenosine
      triphosphatase without such knowledge. The CA RMSD between the best model and its
      crystal structure is only 3.4 A, and its contact accuracy reaches 55%.
      Furthermore, the model correctly identifies the binding pocket for sodium ion.
      These results demonstrate that the method can be readily applied to ab initio
      structure prediction of simple TM helix bundle proteins having modest numbers of
      TM helices.

PMID- 16807903
TI  - Ordering in a glycine-rich peptide conjugate: microscopic, fluorescence, and
      metalation studies.
AB  - Glycine residues play an intriguing role in peptide/protein structure where they
      can act as tightly packing amino acids with flexible bond angles. For example,
      structural role of glycines is highlighted in natural silk fibers where different
      structural polymorphs have been reported. This study deals with a glycine-rich
      segment from the conserved octarepeat (PHGGGWGQ) in prion protein. We have
      synthesized a bis-conjugate 3, containing a truncated pentapeptide segment
      (GGGWG), to study its time-dependent solution phase aggregation by a combination
      of microscopic methods and fluorescence. This discontinuous peptide conjugate 3
      exhibited interesting photophysical properties upon self-assembly allowing us to
      propose a possible model of peptide filament formation. Taking note of the fact
      that prion octarepeats bind copper, we also demonstrate the ability of this
      conjugate to bind copper and the growth and ultrastructure of metallized fibers
      formed upon incubation. Enforcing peptide fiber formation in metal binding motifs
      offers an entry into metal impregnated fibers for possible nanobiotechnological
      applications.

PMID- 16807904
TI  - Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts:
      leukodystrophies arising from astrocyte dysfunction.

PMID- 16807905
TI  - Vanishing white matter disease: a review with focus on its genetics.
AB  - Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive
      brain disorder, most often with a childhood onset. Magnetic resonance imaging and
      spectroscopy indicate that, with time, increasing amounts of cerebral white
      matter vanish and are replaced by fluid. Autopsy confirms white matter
      rarefaction and cystic degeneration. The process of localization and
      identification of the first two genes related to VWM, EIF2B5 and EIF2B2, was
      facilitated by two founder effects in the Dutch population. EIF2B5 and EIF2B2
      encode the epsilon and beta subunits of translation initiation factor eIF2B. Soon
      it was shown that mutations in all five eIF2B subunit genes can cause VWM. EIF2B
      is essential for the initiation of translation of RNA into protein and is
      involved in regulation of the process, especially under stress conditions, which
      may explain the sensitivity to stress conditions observed in VWM patients. The
      pathophysiology of the disease is still poorly understood.

PMID- 16807906
TI  - Inflammation in white matter: clinical and pathophysiological aspects.
AB  - While the central nervous system (CNS) is generally thought of as an
      immunopriviledged site, immune-mediated CNS white matter damage can occur in both
      the perinatal period and in adults, and can result in severe and persistent
      neurological deficits. Periventricular leukomalacia (PVL) is an inflammatory
      white matter disease of premature infants that frequently results in cerebral
      palsy (CP). Clinical and experimental studies show that both hypoxic/ischemic and
      innate immune mechanisms contribute to the destruction of immature
      oligodendroglia and of axons in the deep cerebral white matter in PVL. No data
      are yet available as to whether there is any genetic predisposition to PVL or to
      its neurological sequelae. Multiple sclerosis (MS) is an inflammatory white
      matter disease that often begins in young adulthood, causes multifocal
      destruction of mature oligodendroglia and of axons, and eventually leads to
      substantial cumulative neurological disability. Certain genetic polymorphisms
      contribute to susceptibility to MS, and adaptive immune responses to myelin
      associated self antigens, or to exogenous antigens that mimic these self
      antigens, play a central role in the pathophysiology of this disease.

PMID- 16807907
TI  - Canavan disease: a white matter disorder.
AB  - Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as
      the loss of myelin, results in axonal dysfunction and hence a disruption of
      information processing between brain regions. The major feature of
      leukodystrophies is the lack of proper myelin formation during early development
      or the onset of myelin loss late in life. These early childhood WM diseases are
      described as hypomyelination or dysmyelination arising from a primary block in
      normal myelin synthesis because of a genetic mutation expressed in
      oligodendrocytes, or failure in myelination secondary to neuronal or astroglial
      dysfunctions (van der Knaap 2001 Dev. Med. Child Neurol. 43:705-712). Here, we
      describe the pathophysiological parameters of Canavan disease (CD), caused by
      genetic mutations of the aspartoacylase (ASPA) gene, a metabolic enzyme
      restricted in the central nervous system (CNS) to oligodendrocytes. CD presents
      pathophysiological dysfunctions similar to diseases caused by myelin gene
      mutations, such as Pelizaeus-Merzbacher disease (PMD) and several animal models,
      such as myelin deficient rat (md), jimpy (jp), shiverer (sh), and quaking (qk
      viable) mutant mice. These single gene mutations have pleiotropic effects,
      whereby the alteration of one myelin gene expression disrupts functional
      expression of other oligodendrocyte genes with an outcome of
      hypomyelination/dysmyelination. Among all of the known leukodystrophies, CD is
      the first disorder, which was approved and tested for the adeno-associated virus
      vector (AAV)-ASPA gene therapy (Leone et al. 2000 Ann. Neurol. 48:27-38; Janson
      et al. 2001 Trends Neurosci. 24:706-712) without much success following the first
      two attempts. ASPA gene delivery attempts in animal models have shown a lowering
      of N-acetyl L-aspartate and a change in motor functions, while sponginess of the
      WM, a characteristic of CD remained unchanged (Matalon et al. 2003 Mol. Ther. 7
      (5, Part 1):580-587; McPhee et al. 2005 Brain Res. Mol. Brain Res. 135:112-121)
      even with better viral serotype and delivery of the gene during early phase of
      development (Klugmann et al. 2005 Mol. Ther. 11:745-753). While different
      approaches are being sought for the success of gene therapy, there are pivotal
      developmental questions to address regarding the specific regions of the CNS and
      cell lineages that become the target for the onset and progression of CD symptoms
      from early to late stages of development.

PMID- 16807908
TI  - Preface: white matter disorders.

PMID- 16807909
TI  - The Yin and Yang of cell cycle progression and differentiation in the
      oligodendroglial lineage.
AB  - In white matter disorders such as leukodystrophies (LD), periventricular
      leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the
      remyelination failure by oligodendrocyte progenitor cells involves errors in the
      sequence of events that normally occur during development when progenitors
      proliferate, migrate through the white matter, contact the axon, and
      differentiate into myelin-forming oligodendrocytes. Multiple mechanisms underlie
      the eventual progressive deterioration that typifies the natural history of
      developmental demyelination in LD and PVL and of adult-onset demyelination in MS.
      Over the past few years, pathophysiological studies have mostly focused on
      seeking abnormalities that impede oligodendroglial maturation at the level of
      migration, myelination, and survival. In contrast, there has been a strikingly
      lower interest for early proliferative and differentiation events that are likely
      to be equally critical for white matter development and myelin repair. This
      review highlights the Yin and Yang principles of interactions between intrinsic
      factors that coordinately regulate progenitor cell division and the onset of
      differentiation, i.e. the initial steps of oligodendrocyte lineage progression
      that are obviously crucial in health and diseases.

PMID- 16807910
TI  - Perinatal white matter injury: the changing spectrum of pathology and emerging
      insights into pathogenetic mechanisms.
AB  - Perinatal brain injury in survivors of premature birth has a unique and
      unexplained predilection for periventricular cerebral white matter.
      Periventricular white-matter injury (PWMI) is now the most common cause of brain
      injury in preterm infants and the leading cause of chronic neurological
      morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions
      (periventricular leukomalacia; PVL) and diffuses myelination disturbances. Recent
      neuroimaging studies support that the incidence of PVL is declining, whereas
      focal or diffuse noncystic injury is emerging as the predominant lesion. Factors
      that predispose to PVL during prematurity include hypoxia, ischemia, and maternal
      fetal infection. In a significant number of infants, PWMI appears to be initiated
      by perturbations in cerebral blood flow that reflect anatomic and physiological
      immaturity of the vasculature. Ischemic cerebral white matter is susceptible to
      pronounced free radical-mediated injury that particularly targets immature stages
      of the oligodendrocyte lineage. Emerging experimental data supports that
      pronounced ischemia in the periventricular white matter is necessary, but not
      sufficient to generate PWMI. The developmental predilection for PWMI to occur
      during prematurity appears to be related to both the timing of appearance and
      regional distribution of susceptible oligodendrocyte progenitors. Injury to
      oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by
      disrupting the maturation of myelin-forming oligodendrocytes. Chemical mediators
      that may contribute to white-matter injury include reactive oxygen species
      glutamate, cytokines, and adenosine. As our understanding of the pathogenesis of
      PWMI improves, it is anticipated that new strategies for directly preventing
      brain injury in premature infants will develop.

PMID- 16807911
TI  - Childhood multiple sclerosis: a review.
AB  - Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central
      nervous system (CNS) that is increasingly recognized as a disease that affects
      children. Similar to adult-onset MS, children present with visual and sensory
      complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be
      helpful in diagnosing MS when CSF immunoglobulins and oligoclonal bands are
      present. White matter demyelinating lesions on MRI are required for the
      diagnosis; however, children typically have fewer lesions than adults. Many
      criteria have been proposed to diagnose MS that have been applied to children,
      mostly above 10 years of age. The recent revisions to the McDonald criteria allow
      for earlier diagnosis, such as after a clinically isolated event. However,
      children are more likely than adults to have monosymptomatic illnesses. None of
      the approved disease-modifying therapies used in adult-onset MS have been
      approved for pediatrics; however, a few studies have verified their safety and
      tolerability in children. Although children and adults with MS have similar
      neurological symptoms, laboratory (cerebrospinal fluid) data, and neuroimaging
      findings, the clinical course, pathogenesis, and treatment of childhood onset MS
      require further investigation.

PMID- 16807912
TI  - Chemistry of Ru(eta6-1,3,5-cyclooctatriene)(eta2-dimethyl fumarate)2.
AB  - The chemistry of a novel zerovalent Ru complex, Ru(eta6-cot)(eta2-dmfm)2 (1)
      (cot=1,3,5-cyclooctatriene; dmfm=dimethyl fumarate), is reviewed with a focus on
      its reactivity toward phosphines, amines, and H2O, as well as arenes and p
      quinones. A variety of novel zerovalent Ru complexes were synthesized from
      Ru(eta6-cot)(eta2-dmfm)2 (1), and it was shown that the complexes preferably bear
      both electron-donating and -accepting ligands simultaneously to exhibit
      thermodynamic stability. The first isolable zerovalent Ru aqua complexes were
      successfully prepared, and in these complexes, the generation of a chiral center
      on the O atom of the coordinated H2O was disclosed. In addition, the
      characteristic catalytic activity of 1 in organic synthesis was considered by
      reviewing recently developed novel reactions: (i) dimerization of 2,5
      norbornadiene to pentacyclo[6.6.0.0(2,6).0(3,13).0(10,14)]tetradeca-4,11-diene
      (PCTD), (ii) intramolecular hydroamination of aminoalkynes to cyclic imines,
      (iii) formal [4+2] cycloaddition of alkynes with dmfm to trans-4-cyclohexene-1,2
      dicarboxylates, and (iv) co-dimerization of dihydrofurans with alpha,beta
      unsaturated esters to 2-alkylidenetetrahydrofurans. The products obtained here
      are expected to be used as novel functional organic monomers.

PMID- 16807913
TI  - Hippocampal volumetry: Is a consensus definition of the posterior boundaries
      possible?

PMID- 16807914
TI  - Cerebral metastasis and other central nervous system complications of
      pleuropulmonary blastoma.
AB  - BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare tumor of pleura and lung in
      young children. Central nervous system (CNS) complications, particularly cerebral
      parenchymal metastases, occur in aggressive forms of PPB: Types II and III PPB.
      This article evaluates cerebral and meningeal metastases, cerebrovascular events
      (CVA) caused by tumor emboli, spinal cord complications, and intracranial second
      malignancies in PPB. PROCEDURE: International PPB Registry and literature cases
      were evaluated for CNS events. Cerebral metastasis patients were evaluated for
      gender, side of origin of PPB, PPB Type, interval from diagnosis to metastasis,
      status of chest disease, treatment, and outcome. Standard statistical methods
      were used to calculate the cumulative probability of cerebral metastasis and
      survival following metastasis. RESULTS: Thirty-nine cases of cerebral metastasis
      were identified in 5/53 Registry Type II cases, 15/44 Registry Type III cases,
      and 19/143 literature Type II/III cases. Metastases occurred 1-60, median 11.5
      months after diagnosis. Chest disease was controlled in 50% of children at time
      of metastasis. The cumulative probability of cerebral metastasis by 5 years from
      diagnosis was 11% for Type II patients (95%CI (confidence interval): 2-20%) and
      54% for Type III patients (95%CI: 31-76%). Seven children survive cerebral
      metastasis. Other CNS complications were post-operative CVA (five cases), spinal
      cord invasion or compression (six), leptomeningeal disease (three), and second
      intracranial malignancies (two). CONCLUSIONS: Cerebral metastasis is more
      frequent in PPB than in other childhood sarcomas. Clinicians should screen for
      this complication. Diverse other CNS complications are less common and require
      careful diagnosis.

PMID- 16807915
TI  - Postnatal respiratory distress in a dichorial twin with congenital thoracic
      neuroblastoma after assisted reproduction by intracytoplasmatic sperm injection.
AB  - We report on the case of a female twin with congenital thoracic neuroblastoma
      after conception via intracytoplasmatic sperm injection (ICSI). Birth occurred at
      37 + 1-week gestation per primary sectio caesarea. Acute respiratory distress
      necessitated intubation and mechanical ventilation. Ultrasound and magnetic
      resonance imaging (MRI) showed a mass in the right upper thorax compressing the
      trachea. The tumor was subtotally excised and histological analysis revealed
      neuroblastoma. No further treatment was given. The residual primary tumor
      regressed spontaneously. Four years after diagnosis, both twins are healthy and
      normally developed.

PMID- 16807917
TI  - A biophysical model of the male urethra: comparing viscoelastic properties of
      polyvinyl alcohol urethras to male pig urethras.
AB  - AIMS: We aim at developing a non-invasive method for grading and diagnosing
      urinary bladder outlet obstruction, based on noise recording with a perineal
      contact microphone during voiding. We found that the noise production during
      voiding depends amongst others on the viscoelastic properties of the urethral
      wall. To further test our method, we need a realistic biophysical model of the
      male urethra. METHODS: We made various model urethras with different viscoelastic
      properties from a 10% aqueous solution of polyvinyl alcohol cryogel. We measured
      the viscoelastic properties of each model and compared them to those of the male
      pig urethra. The male pig urethra was used, as it is physiologically comparable
      to the human male urethra. The viscoelastic properties of both model and pig
      urethras were measured by applying strain to the urethral wall in a stepwise
      manner and recording the pressure response. We fitted the step-response of a
      mechanical model to this pressure response and derived the viscoelastic
      properties from the coefficients of this response. RESULTS: A uniform model
      urethra that was freeze-thawed three times, with a Y-shaped flow channel was
      found to best represent the male pig urethra. CONCLUSIONS: We consider the three
      times freeze-thawed model urethra with a Y-shaped flow channel the best model of
      the human male urethra. And we therefore use this model urethra for studying the
      relation between noise recording during urine flow and the degree of bladder
      outlet obstruction.

PMID- 16807918
TI  - Structural models of the snake venom factor V activators from Daboia russelli and
      Daboia lebetina.
AB  - Blood coagulation factor V (FV) is a multifunctional protein that circulates in
      human plasma as a precursor molecule which can be activated by thrombin or
      activated factor X (FXa) in order to express its cofactor activity in prothrombin
      activation. FV activation is achieved by limited proteolysis after Arg709,
      Arg1018, and Arg1545 in the FV molecule. The venoms of Daboia russelli and Daboia
      lebetina contain a serine protease that specifically activates FV by a single
      cleavage at Arg1545. We have predicted the three-dimensional structure of these
      enzymes using comparative protein modeling techniques. The plasminogen activator
      from Agkistrodon acutus, which shows a high degree of homology with the venom FV
      activators and for which a high-quality crystallographic structure is available,
      was used as the molecular template. The RVV-V and LVV-V models provide for the
      first time a detailed and accurate structure of a snake venom FV activator and
      explain the observed sensitivity or resistance toward a number of serine protease
      inhibitors. Finally, electrostatic potential calculations show that two
      positively charged surface patches are present on opposite sides of the active
      site. We propose that both FV activators achieve their exquisite substrate
      specificity for the Arg1545 site via interactions between these exosites and FV.

PMID- 16807916
TI  - Repetitive cycles of high-dose cytarabine are effective for childhood acute
      myeloid leukemia: long-term outcome of the children with AML treated on two
      consecutive trials of Tokyo Children's Cancer Study Group.
AB  - BACKGROUND: Various methods of intensive chemotherapy have contributed to an
      improved survival in pediatric acute myeloid leukemia (AML). We here report the
      long-term results of the two consecutive trials of Tokyo Children's Cancer Study
      Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C)
      based combination chemotherapy in post-remission phase. PROCEDURE: A total of 216
      eligible children with newly diagnosed AML were treated in the two consecutive
      multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September
      1998. In M91-13 trial, patients received eight courses of intensive post
      remission chemotherapy, including six HD-Ara-C containing courses, after
      remission-induction therapy. Autologous hematopoietic stem cell transplantation
      (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated
      if donor was available. In M96-14 trial, the last two HD-Ara-C courses were
      omitted from the chemotherapy arm. RESULTS: The remission-induction rate was
      88.8% and probability of 5-year Overall survival (OS) and event-free survival
      (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%),
      respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without
      Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21)
      or inv(16) was a significant good prognostic factor both in the univariate and
      multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a
      good survival exceeding 70% in 5 years. CONCLUSIONS: These results suggest that
      repetitive use of HD-Ara-C was effective and safe for childhood AML. However,
      further optimization of AML therapy is required.

PMID- 16807919
TI  - Transition state of a SH3 domain detected with principle component analysis and a
      charge-neutralized all-atom protein model.
AB  - The src SH3 domain has been known to be a two-state folder near room temperature.
      However, in a previous study with an all-atom model simulation near room
      temperature, the transition state of this protein was not successfully detected
      on a free-energy profile using two axes: the radius of gyration (R(g)) and native
      contact reproduction ratio (Q value). In this study, we focused on an atom
      packing effect to characterize the transition state and tried another analysis to
      detect it. To explore the atom packing effect more efficiently, we introduced a
      charge-neutralized all-atom model, where all of the atoms in the protein and
      water molecules were treated explicitly, but their partial atomic charges were
      set to zero. Ten molecular dynamics simulations were performed starting from the
      native structure at 300 K, where the simulation length of each run was 90 ns, and
      the protein unfolded in all runs. The integrated trajectories (10 x 90 = 900 ns)
      were analyzed by a principal component analysis (PCA) and showed a clear free
      energy barrier between folded- and unfolded-state conformational clusters in a
      conformational space generated by PCA. There were segments that largely deformed
      when the conformation passed through the free-energy barrier. These segments
      correlated well with the structural core regions characterized by large phi
      values, and the atom-packing changes correlated with the conformational
      deformations. Interestingly, using the same simulation data, no significant
      barrier was found in a free-energy profile using the R(g) and Q values for the
      coordinate axes. These results suggest that the atom packing effect may be one of
      the most important determinants of the transition state.

PMID- 16807920
TI  - Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet.
AB  - OBJECTIVE: The full anticonvulsant effect of the ketogenic diet (KD) can require
      weeks to develop in rats, suggesting that altered gene expression is involved.
      The KD typically is used in pediatric epilepsies, but is effective also in
      adolescents and adults. Our goal was to use microarray and complementary
      technologies in adolescent rats to understand its anticonvulsant effect. METHODS:
      Microarrays were used to define patterns of gene expression in the hippocampus of
      rats fed a KD or control diet for 3 weeks. Hippocampi from control- and KD-fed
      rats were also compared for the number of mitochondrial profiles in electron
      micrographs, the levels of selected energy metabolites and enzyme activities, and
      the effect of low glucose on synaptic transmission. RESULTS: Most striking was a
      coordinated upregulation of all (n = 34) differentially regulated transcripts
      encoding energy metabolism enzymes and 39 of 42 transcripts encoding
      mitochondrial proteins, which was accompanied by an increased number of
      mitochondrial profiles, a higher phosphocreatine/creatine ratio, elevated
      glutamate levels, and decreased glycogen levels. Consistent with increased energy
      reserves, synaptic transmission in hippocampal slices from KD-fed animals was
      resistant to low glucose. INTERPRETATION: These data show that a calorie
      restricted KD enhances brain metabolism. We propose an anticonvulsant mechanism
      of the KD involving mitochondrial biogenesis leading to enhanced alternative
      energy stores.

PMID- 16807921
TI  - Shorter telomeres are associated with mortality in those with APOE epsilon4 and
      dementia.
AB  - OBJECTIVE: Reduced telomere length may be a marker of biological aging. We
      hypothesized that telomere length might thus relate to increased risk for
      dementia and mortality. METHODS: This nested case-control study used stored
      leukocyte DNA from 257 individuals (mean age, 81.4 +/- 7.9 years; 64.6% female;
      44.7% Hispanic, 33.5% non-Hispanic black, and 21.8% non-Hispanic white). Our
      assay used real-time polymerase chain reaction, with two separate reactions
      amplifying telomere sequence and reference single copy gene (ribosomal-protein
      P0), providing a calculated telomere-to-single copy gene (T/S) ratio. RESULTS:
      Mean telomere length was shorter among subjects dying during follow-up than in
      those surviving (0.453 +/- 0.211 vs 0.525 +/- 0.226 [+/- standard deviation]; p <
      0.009). It was also shorter in those with Alzheimer's disease compared with
      control subjects (0.458 +/- 0.207 vs 0.516 +/- 0.229; p < 0.03). For participants
      with Alzheimer's disease, compared with those with the longest telomeres, the
      mortality odds ratio (OR) was 4.8 (95% confidence interval [CI], 1.7-13.8) in
      those with intermediate-length telomeres and 7.3 (95% CI, 2.4-22.0) in those with
      the shortest telomeres. The presence of an epsilon4 allele also increased the
      mortality OR, with an OR of 5.8 (95% CI, 1.3-26.4) for intermediate-length
      telomeres and an OR of 9.0 (95% CI, 1.9-41) for the shortest telomeres.
      INTERPRETATION: Our findings suggest that leukocyte telomere length is related to
      both dementia and mortality and may be a marker of biological aging.

PMID- 16807922
TI  - GlycoVis: visualizing glycan distribution in the protein N-glycosylation pathway
      in mammalian cells.
AB  - Glycosylation has profound effects on the quality of recombinant proteins
      produced in mammalian cells. The biosynthetic pathways of N-linked glycans on
      glycoproteins involves a relatively small number of enzymes and nucleotide
      sugars. Many of these glycoconjugate enzymes can utilize multiple N-glycans as
      substrates, thus generating a large number of glycan intermediates, and making
      the biosynthetic pathway resemble a network with diverging and converging paths.
      The N-glycans on secreted glycoprotein molecules include not only terminal
      glycans, but also pathway intermediates. To better assess the glycan distribution
      and the potential route of their synthesis, we created GlycoVis, a visualization
      program that displays the distribution and the potential reaction paths leading
      to each N-glycan on the reaction network. The substrate specificities of the
      enzymes involved were organized into a relationship matrix. With the input of
      glycan distribution data, the program outputs a reaction pathway map which labels
      the relative abundance levels of different glycans with different colors. The
      program also traces all possible reaction paths leading to each glycan and
      identifies each pathway on the map. Glycoform distribution of Chinese Hamster
      Ovary cell-derived tissue plasminogen activator (TPA), and human and mouse IgG
      were used as illustrations for the application of GlycoVis. In addition, the
      intracellular and secreted IgG from an NS0 producer cell line were isolated, and
      their glycoform profiles were displayed using GlycoVis for comparison. This
      visualization tool facilitates the analysis of potential reaction paths utilized
      under different physiological or culture conditions, and may provide insight on
      the potential targets for metabolic engineering.

PMID- 16807923
TI  - Proteomic methods applied to the analysis of immobilized biocatalysts.
AB  - Methods adapted from proteomics can directly characterize proteins present in
      immobilized biocatalysts. Complete hydrolysis followed by HPLC analysis of Tyr
      and Phe estimates total protein bound, and is preferable to conventional
      difference methods, as tested with subtilisin Carlsberg on silica. This new
      method shows that various treatments give quantitative desorption of proteins
      immobilized by adsorption. Intact desorbed proteins may be analyzed by
      electrospray mass spectrometry. The Candida antarctica lipase B from Novozyme 435
      was shown to be heavily glycosylated, while the lipase from Lipozyme RM IM was a
      mixture of four N-terminally truncated forms. Peptides from selective cleavage
      were analyzed by tandem mass spectrometry, leading to automatic identification of
      proteins present. A second major protein present in Lipozyme RM IM was thus found
      to be alpha-amylase from Aspergillus oryzae. These methods should be valuable
      complements to activity measurements in understanding immobilized enzyme activity
      and stability.

PMID- 16807924
TI  - Kinetics of Lactococcus lactis growth and metabolite formation under aerobic and
      anaerobic conditions in the presence or absence of hemin.
AB  - The study of batch kinetics of Lactococcus lactis cell growth and product
      formation reveals three distinct metabolic behaviors depending upon the
      availability of oxygen to the culture and the presence of hemin in the medium.
      These three cultivation modes, anerobic homolactic fermentation, aerobic
      heterolactic fermentation, and hemin-stimulated respiration have been studied at
      pH 6.0 and 30 degrees C with a medium containing a high concentration of glucose
      (60 g/L). A maximum cell density of 5.78 g/L was obtained in the batch culture
      under hemin-stimulated respiration conditions, about three times as much as that
      achieved with anerobic homolactic fermentation (1.87 g/L) and aerobic
      heterolactic fermentation (1.80 g/L). The maximum specific growth rate was 0.60/h
      in hemin-stimulated respiration, slightly higher than that achieved in homolactic
      fermentation (0.56/h) and substantially higher than that in heterolactic
      fermentation (0.40/h). Alteration of metabolism caused by the supplementation of
      oxygen and hemin is evidenced by changes in both cell growth kinetics and
      metabolite formation kinetics, which are characterized by a unique pseudo-diauxic
      growth of L. lactis. We hypothesise that Lactococcus lactis generates bioenergy
      (ATP) through simultaneous lactate formation and hemin-stimulated respiration in
      the primary exponential phase, when glucose is abundant, and utilizes lactate for
      cell growth and cell maintenance in the stationary phase, after glucose is
      exhausted. We also examined the applicability of a modified logistic model and
      the Luedeking-Piret model for cell growth kinetics and metabolite formation
      kinetics, respectively.

PMID- 16807925
TI  - Metabolic analysis of adaptive evolution for in silico-designed lactate-producing
      strains.
AB  - Experimental evolution is now frequently applied to many biological systems to
      achieve desired objectives. To obtain optimized performance for metabolite
      production, a successful strategy has been recently developed that couples
      metabolic engineering techniques with laboratory evolution of microorganisms.
      Previously, we reported the growth characteristics of three lactate-producing,
      adaptively evolved Escherichia coli mutant strains designed by the OptKnock
      computational algorithm. Here, we describe the use of (13)C-labeled experiments
      and mass distribution measurements to study the evolutionary effects on the
      fluxome of these differently designed strains. Metabolic flux ratios and
      intracellular flux distributions as well as physiological data were used to
      elucidate metabolic responses over the course of adaptive evolution and metabolic
      differences among strains. The study of 3 unevolved and 12 evolved engineered
      strains as well as a wild-type strain suggests that evolution resulted in
      remarkable improvements in both substrate utilization rate and the proportion of
      glycolytic flux to total glucose utilization flux. Among three strain designs,
      the most significant increases in the fraction of glucose catabolized through
      glycolysis (>50%) and the glycolytic fluxes (>twofold) were observed in
      phosphotransacetylase and phosphofructokinase 1 (PFK1) double deletion (pta-
      pfkA) strains, which were likely attributed to the dramatic evolutionary increase
      in gene expression and catalytic activity of the minor PFK encoded by pfkB. These
      fluxomic studies also revealed the important role of acetate synthetic pathway in
      anaerobic lactate production. Moreover, flux analysis suggested that independent
      of genetic background, optimal relative flux distributions in cells could be
      achieved faster than physiological parameters such as nutrient utilization rate.

PMID- 16807926
TI  - Stable expression of a heterogeneous gene introduced via gene targeting into the
      HPRT locus of human fibrosarcoma cells.
AB  - To obtain a cell line that maintains stability of gene expression is important
      for industrial production of therapeutic proteins from recombinant cells. In this
      study, we attempted to improve the stability of expression of an exogenous gene
      by using the gene-targeting method in cultured cells. In our gene-targeting
      system, the green fluorescent protein (GFP) gene was used as an exogenous
      reporter gene targeted to the locus of the endogenous hypoxanthine phosphoribosyl
      transferase (HPRT) gene, which is constitutively expressed. Cell lines selected
      using markers of the targeting DNA were cultivated for 129 days without any drug
      selection, and the expression levels of GFP protein and the chromosomal structure
      of the gfp gene in these cell lines were evaluated. Cell lines in which gfp genes
      were randomly integrated into the genome showed decreased GFP expression, which
      resulted from loss of genes or attenuation of transcription. In contrast, cell
      lines in which the gfp gene was targeted to the hprt locus maintained a stable
      chromosomal structure and stable expression of the gfp gene, even after prolonged
      cultivation. These results suggest that constitutively expressed endogenous gene
      loci may be suitable positions for stable expression of exogenous genes, and that
      the gene-targeting strategy presented here may be useful for generation of cell
      lines for industrial protein production.

PMID- 16807927
TI  - A high-rate perfusion bioreactor for plant cells.
AB  - A perfusion bioreactor allowing continuous extraction of secondary metabolites
      was designed and challenged for Eschscholtzia californica plant cell suspensions.
      Four sedimentation columns mounted inside a 2.5-L bioreactor separated single
      cells and cell aggregates from the culture medium. Cells were elicited with
      chitin at day 4 and the liquid medium free of cells and debris was then
      continuously pumped to the extraction columns containing fluidized XAD-7 resins,
      and then recirculated back to the cell suspension. A medium upward velocity
      corresponding to cell sedimentation velocity maintained a stable cell/medium
      separation front in the columns for sedimented cell volume (SCV) of 90% (70%
      packed cell volume, PCV). Two perfusion bioreactor cultures of 10 and 14 days
      were performed. A maximum dilution rate of 20.4/day was reached from day 4 to day
      6, and was then reduced to 5/day at day 9 for 55% SCV. Control cultures were
      performed without and with free extraction resins into the cell suspension.
      Perfusion cultures showed similar specific growth rates of 0.24 +/- 0.04/day
      before and after elicitation. However, production level in the perfusion cultures
      was similar to that from the culture without resins with a maximum of 2.06
      micromole/gDW total alkaloids, with 1.54 micromole/gDW in the resins. Cultures
      with free resins resulted in 30.94 micromole/gDW with 28.4 +/- 8.8 micromole/gDW
      in the resins. Difference in the cells nutritional state from elicitation was
      identified as a major cause in the production reduction. However, pathway to
      chelilutine was favored in the continuous extraction culture.

PMID- 16807928
TI  - Development and characterization of a small-scale bioreactor based on a
      bioartificial hepatic culture model for predictive pharmacological in vitro
      screenings.
AB  - A vast majority of pharmacons are beset by possible interactions and side effects
      which have usually been tested in laboratory animals. However, better methods are
      needed to reduce the number of animal experiments and interspecies differences
      with respect to drug metabolism, as well as to provide a faster and more cost
      effective way of analysis. These facts have led to the development of in vitro
      models based on isolated primary hepatocytes to better assess drug metabolism,
      interactions, and toxicity. A new small-scale bioreactor with the hepatic
      sandwich model and a gas-permeable membrane at the bottom allowing a definable
      oxygen exchange, has been constructed and compared with the conventional well
      plates. Compared to hepatocytes cultured in conventional systems, the cells
      exhibited a stronger liver-specific capacity and remained in a differentiated
      state in the small-scale bioreactor over a cultivation period of 17 days. This in
      vitro model could serve as a tool to predict the liver response to newly
      developed drugs.

PMID- 16807929
TI  - Sulfide oxidation under chemolithoautotrophic denitrifying conditions.
AB  - Chemolithoautotrophic denitrifying microorganisms oxidize reduced inorganic
      sulfur compounds coupled to the reduction of nitrate as an electron acceptor.
      These denitrifiers can be applied to the removal of nitrogen and/or sulfur
      contamination from wastewater, groundwater, and gaseous streams. This study
      investigated the physiology and kinetics of chemolithotrophic denitrification by
      an enrichment culture utilizing hydrogen sulfide, elemental sulfur, or
      thiosulfate as electron donor. Complete oxidation of sulfide to sulfate was
      observed when nitrate was supplemented at concentrations equal or exceeding the
      stoichiometric requirement. In contrast, sulfide was only partially oxidized to
      elemental sulfur when nitrate concentrations were limiting. Sulfide was found to
      inhibit chemolithotrophic sulfoxidation, decreasing rates by approximately 21
      fold when the sulfide concentration increased from 2.5 to 10.0 mM, respectively.
      Addition of low levels of acetate (0.5 mM) enhanced denitrification and sulfate
      formation, suggesting that acetate was utilized as a carbon source by
      chemolithotrophic denitrifiers. The results of this study indicate the potential
      of chemolithotrophic denitrification for the removal of hydrogen sulfide. The
      sulfide/nitrate ratio can be used to control the fate of sulfide oxidation to
      either elemental sulfur or sulfate.

PMID- 16807930
TI  - Asymmetric allylic substitution catalyzed by C1-symmetrical complexes of
      molybdenum: structural requirements of the ligand and the stereochemical course
      of the reaction.
AB  - Application of new chiral ligands (R)-(-)-12 a and (S)-(+)-12 c (VALDY), derived
      from amino acids, to the title reaction, involving cinnamyl (linear) and
      isocinnamyl (branched) type substrates (4 and 5 --> 6), led to excellent regio-
      and enantioselectivities (>30:1, < or =98 % ee), showing that ligands with a
      single chiral center are capable of high asymmetric induction. The structural
      requirements of the ligand and the mechanism are discussed. The application of
      single enantiomers of deuterium-labeled substrates (both linear 38 c and branched
      37 c) and analysis of the products (41-43) by (2)H{(1)H} NMR spectroscopy in a
      chiral liquid crystal matrix allowed the stereochemical pathways of the reaction
      to be distinguished. With ligand (S)-(+)-12 c, the matched enantiomer of branched
      substrate was found to be (S)-5, which was converted into (R)-6 with very high
      regio- and stereoselectivity via a process that involves net retention of
      stereochemistry. The mismatched enantiomer of the branched substrate was found to
      be (R)-5, which was also converted into (R)-6, that is, with apparent net
      inversion, but at a lower rate and with lower overall enantioselectivity. This
      latter feature, which may be termed a "memory effect", reduced the global
      enantioselectivity in the reaction of the racemic substrate (+/-)-5. The
      stereochemical pathway of the mismatched manifold has been shown also to be one
      of net retention, the apparent inversion occurring through equilibration via an
      Mo-allyl intermediate prior to nucleophilic attack. Incomplete equilibration
      leads to the memory effect and thus to lower enantioselectivity. Analysis of the
      mismatched manifold over the course of the reaction revealed that the memory
      effect is progressively attenuated with the nascent global selectivity increasing
      substantially as the reaction proceeds. The origin of this effect is suggested to
      be the depletion of CO sources in the reaction mixture, which attenuates turnover
      rate and thus facilitates greater equilibrium. The linear substrate was also
      converted into the branched product with net syn stereochemistry, as shown by
      isotopic labeling. An analogous process operates in the generation of small
      quantities of linear product from branched substrate.

PMID- 16807931
TI  - Towards perfunctionalized dodecahedranes--en route to C20 fullerene.
AB  - "One-pot" substitution of the twenty hydrogen atoms in pentagonal dodecahedrane
      (C(20)H(20)) by OH, F, Cl, and Br atoms is explored. Electrophilic insertion of
      oxygen atoms with DMDO and TFMDO as oxidizing reagents ended, far off the desired
      C(20)(OH)(20), in complex polyol mixtures (up to C(20)H(10)(OH)(10) decols, a
      trace of C(20)H(OH)(19)?). Perfluorination was successful in a NaF matrix but
      (nearly pure) C(20)F(20) could be secured only in very low yield. "Brute-force"
      photochlorination (heat, light, pressure, time) provided a mixture of hydrogen
      free, barely soluble C(20)Cl(16) dienes in high yield and C(20)Cl(20) as a trace
      component. Upon electron-impact ionization of the C(20)Cl(16) material sequential
      loss of the chlorine atoms was the major fragmentation pathway furnishing,
      however, only minor amounts of chlorine-free C(20) (+) ions. "Brute-force"
      photobrominations delivered an extremely complex mixture of polybromides with
      C(20)HBr(13) trienes as the highest masses. The MS spectra exhibited exclusive
      loss of the Br substituents ending in rather intense singly, doubly, and triply
      charged C(20)H(4-0) (+(2+)(3+)) ions. The insoluble approximately C(20)HBr(13)
      fraction (C(20)Br(14) trienes as highest masses) obtained along a modified
      bromination protocol, ultimately allowed the neat mass selection of C(20) (-)
      ions. The C(20)Cl(16) dienes and C(20)H(0-3)Br(14-12) tri-/tetraenes, in spite of
      their very high olefinic pyramidalization, proved resistant to oxygen and
      dimerization (polymerization) but added CH(2)N(2) smoothly. Dehalogenation of the
      respective cycloaddition products through electron-impact ionization resulted in
      C(22-24)H(4-8) (+(2+)) ions possibly constituting bis-/tris-/tetrakis-methano
      C(20) fullerenes or partly hydrogenated C(22), C(23), and C(24) cages.

PMID- 16807932
TI  - Combination of 768-well microplate array diagonal gel electrophoresis with duplex
      PCR of X and Y chromosome markers for quality control of epidemiological DNA
      banks.
AB  - Large DNA banks for human epidemiological studies have become an increasingly
      important research tool. The power of genotype-phenotype studies is dependent
      both on the quality of phenotyping and of genotyping and of correct linking of
      phenotypes to genotypes. Samples must be tracked through numerous steps between
      subject or patient and post-genotypic data. Only one phenotype, sex, has a
      perfect and binary correlation with genotype. In mixed sex studies, it may be
      advantageous for purposes of quality control to keep sexes mixed during the steps
      from acquisition to DNA bank, in order to be able to check later for sample
      swaps. We have designed a duplex PCR combining an amplicon from MAOA marking the
      X chromosome and an amplicon from DDX3Y marking the Y chromosome. We combined
      this with a simple economical palmtop sized 768-well microplate compatible
      electrophoresis system developed in-house for examination of duplex PCR products.
      We applied this quality control test in the validation of two DNA banks.

PMID- 16807933
TI  - Evaluation of whole-genome amplification of low-copy-number DNA in chimerism
      analysis after allogeneic stem cell transplantation using STR marker typing.
AB  - Whole-genome DNA amplification (WGA) is a promising method that generates large
      amounts of DNA from samples of limited quantity. We investigated the accuracy of
      a multiplex PCR approach to WGA over STR loci. The amplification bias within a
      locus and over all analyzed loci was investigated in relation to the amount of
      template in the WGA reaction, the specific STR locus, and allele length. We
      observed reproducible error-free STR profiles with 10 ng down to 1 ng of DNA
      template. The amplification deviation at a locus and between loci was within the
      intra-method reproducibility. WGA is the method of choice for amplifying nanogram
      amounts of genomic DNA for different applications. We detected unbalanced STR
      amplifications at one locus and between loci, allelic drop-outs, and additional
      alleles after WGA of low-copy-number DNA. We found that the high number of drop
      outs and drop-ins could be eradicated using pooled DNA from separate WGA
      reactions even with as little as 100 pg of starting template. Nevertheless, the
      quality of the results was still not sufficient for use in routine chimerism
      analysis of limited specific cell populations after allogeneic stem cell
      transplantation.

PMID- 16807934
TI  - On-chip chiral separation based on bovine serum albumin-conjugated carbon
      nanotubes as stationary phase in a microchannel.
AB  - A novel method of chiral separation based on protein-stationary phase immobilized
      in a poly(methyl methacrylate) microfluidic chip was developed. BSA conjugated
      with the shortened carboxylic single-walled carbon nanotubes (SWNTs) was employed
      as the chiral selector. Successful separation of tryptophan enantiomers was
      achieved in less than 70 s with a resolution factor of 1.35 utilizing a
      separation length of 32 mm. This is the first example of chiral separation based
      on SWNTs-BSA conjugates as stationary phase immobilized in microchip channel. The
      stability of the stationary phase in the channel was examined by microchip
      electrophoresis with laser-induced fluorescence detection. Factors that
      influenced the chiral separation resolution were examined. Under the optimized
      conditions, the proposed modified chip revealed adequate repeatability concerning
      run-to-run. These results show that the use of SWNTs-BSA conjugates within
      microfluidic channels hold great promise for a variety of analytical schemes.

PMID- 16807935
TI  - A new approach for the removal of protein impurities from purified biologicals
      using combinatorial solid-phase ligand libraries.
AB  - The removal of last impurity traces from a purified protein is generally called
      polishing. It is an important step in downstream processing since protein
      impurities may generate undesirable side effects when the preparation is intended
      for research, diagnostic and more importantly therapeutic applications. Polishing
      is generally achieved by using orthogonal separation methods to previous steps,
      the most common being gel permeation chromatography. In spite of its polishing
      effectiveness, this technique suffers from a poor separation capacity and modest
      productivity as a result of low speed. Other approaches, for instance, based on
      anion exchange or on hydrophobic chromatography, that may be optimized for a
      given process cannot be used as generic methods. This document reports for the
      first time the use of a combinatorial solid-phase peptide library as a general
      method for the removal of impurity traces. Several examples of impurity trace
      removal are reported; starting material is either a pure protein spiked with
      serum proteins or with Escherichia coli extracts or current purified proteins
      still containing a small percentage of impurities. Among polished proteins are
      recombinant human albumin expressed in Pichia pastoris and human transferrin
      purified from whole plasma. This new method is used in neutral or even
      physiological pH and ionic strength conditions, with a remarkable capability to
      remove impurities. The process is as rapid as current adsorption chromatography
      procedures usable for the removal of a large number of protein impurities, with
      each one present in small amounts, such as host cell proteins.

PMID- 16807936
TI  - Comparison of oligonucleotide migration in a bicontinuous cubic phase of
      monoolein and water and in a fibrous agarose hydrogel.
AB  - Porous hydrogels such as agarose are commonly used to analyze DNA and water
      soluble proteins by electrophoresis. More recently lyotropic liquid crystals,
      such as the diamond cubic phase formed by the lipid monoolein and water, has
      become a new type of well-defined porous structure of interest for both
      hydrophilic and amphiphilic analytes. Here we compare these two types of matrixes
      by investigating the nature of retardation they confer to an oligonucleotide that
      migrates in their respective aqueous phases. The retardation for a 25-mer
      oligonucleotide was found to be about 35-fold stronger in the cubic phase than in
      an agarose hydrogel modified to have the same average pore size. According to
      modelling, the strong retardation is primarily due to the fact that hydrodynamic
      interaction with the continuous monoolein membrane is a stronger source of
      friction than the steric interactions (collisions) with discrete gel fibres. A
      secondary effect is that the regular liquid crystal has a narrower pore-size
      distribution than the random network of the agarose gel. In agreement with
      experiments, these two effects together predict that the retardation in the cubic
      phase is a 30-fold stronger than in an agarose gel with the same average pore
      radius.

PMID- 16807937
TI  - Preparative capillary zone electrophoresis using a dynamic coated wide-bore
      capillary.
AB  - Preparative capillary zone electrophoresis separations of cytochrome c from
      bovine and horse heart are performed efficiently in a surfactant-coated
      capillary. The surfactant, dimethylditetradecylammonium bromide (2C(14)DAB),
      effectively eliminated protein adsorption from the capillary surface, such that
      symmetrical peaks with efficiencies of 0.7 million plates/m were observed in 50
      microm id capillaries when low concentrations of protein were injected. At
      protein concentrations greater than 1 g/L, electromigration dispersion became the
      dominant source of band broadening and the peak shape distorted to triangular
      fronting. Matching of the mobility of the buffer co-ion to that of the cytochrome
      c resulted in dramatic improvements in the efficiency and peak shape. Using 100
      mM bis(2-hydroxyethyl)imino-tris(hydroxymethyl)methane phosphate buffer at pH 7.0
      with a 100-microm id capillary, the maximum sample loading capacity in a single
      run was 160 pmol (2.0 microg) of each protein.

PMID- 16807938
TI  - Studying protein-drug interaction by microfluidic chip affinity capillary
      electrophoresis with indirect laser-induced fluorescence detection.
AB  - We developed a microfluidic chip-affinity CE method based on indirect LIF
      detection to study protein-drug interactions. The interaction between heparin and
      BSA was quantitatively studied, as a model system. In our method, sodium
      fluorescein was chosen as background, and redistilled water as marker to monitor
      EOF. The electrophoretic mobility changes of BSA were measured, with various
      concentrations of heparin added to the running buffer. Each run was completed
      within 80 s. The binding constant was determined to be (1.24 +/- 0.05) x 10(3) M(
      1), which was in good agreement with that reported in the literature.

PMID- 16807939
TI  - A simple protocol for protein extraction of recalcitrant fruit tissues suitable
      for 2-DE and MS analysis.
AB  - Fruit tissues are considered recalcitrant plant tissue for proteomic analysis.
      Three phenol-free protein extraction procedures for 2-DE were compared and
      evaluated on apple fruit proteins. Incorporation of hot SDS buffer, extraction
      with TCA/acetone precipitation was found to be the most effective protocol. The
      results from SDS-PAGE and 2-DE analysis showed high quality proteins. More than
      500 apple polypeptides were separated on a small scale 2-DE gel. The successful
      protocol was further tested on banana fruit, in which 504 and 386 proteins were
      detected in peel and flesh tissues, respectively. To demonstrate the quality of
      the extracted proteins, several protein spots from apple and banana peels were
      cut from 2-DE gels, analyzed by MS and have been tentatively identified. The
      protocol described in this study is a simple procedure which could be routinely
      used in proteomic studies of many types of recalcitrant fruit tissues.

PMID- 16807941
TI  - Proteomic and bioinformatic analysis of iron- and sulfur-oxidizing
      Acidithiobacillus ferrooxidans using immobilized pH gradients and mass
      spectrometry.
AB  - A comparative analysis of the protein composition of Acidithiobacillus
      ferrooxidans cells grown on elemental sulfur and ferrous iron was performed. A
      newly developed protocol involving immobilized pH gradients, improved protein
      reduction, mass spectrometry protein identification and full genome sequence
      information was applied. This approach resulted in more than 1300 protein spots
      displayed in broad and basic pH ranges, the best A. ferrooxidans proteome
      resolution to date. A comparative image analysis revealed that the proteome was
      significantly influenced by the growth type, and allowed for the detection of
      many physiologically important proteins. Among them were sulfate
      adenylyltransferase and sulfide dehydrogenase, which are involved in sulfate
      assimilation and sulfide metabolism, respectively. Many other proteins were
      related to important processes like cell attachment and electron transport. Co
      migration of phosphate and sulfate transport proteins was also observed.

PMID- 16807942
TI  - Proteomic examination of Ralstonia eutropha in cellular responses to formic acid.
AB  - In this study, Ralstonia eutropha was used to elucidate protein changes in
      response to formic acid. Sixty-three differentially expressed proteins in
      relation to formic acid in R. eutropha were found with 1-D PAGE and nano-LC
      MS/MS. Among the proteins with decreased expression, four were involved in the
      shikimate pathway and three proteins in the pyrimidine biosynthesis pathway. With
      the increased expression of proteins, a dramatic change occurred in the induction
      of ion transporters in relation to maintenance of the acid-base balance. A
      detoxification process of formic acid in the bacteria might be related to a
      membrane enzyme, formate hydrogenylase. Three proteins in polyhydroxyalkanoate
      synthesis were enhanced and five proteins in glutathione biosynthesis increased
      in response to formic acid. Three enzymes in mevalonate biosynthesis and heat
      shock proteins were also elevated in the cells. Therefore, formic acid might have
      an inhibitory effect on aromatic amino acid production and pyrimidine
      biosynthesis in R. eutropha. R. eutropha cells seemed to attempt to overcome the
      effects of formic acid by increasing ion transporters and proteins that
      metabolized formic acid.

PMID- 16807940
TI  - Characterization of the human urine proteome by preparative electrophoresis in
      combination with 2-DE.
AB  - The protein components of urine are useful indicators of renal function and human
      health in general. Urine samples are easily attainable making them ideal
      substrates for biomarker research. Analysis of the urine proteome however, has
      been hindered by the great variability of the urine specimens, and the presence
      of various proteins in low abundance or modified forms. To alleviate some of
      these problems urine samples from five different individuals were pooled,
      concentrated and the proteome characterized by a combination of preparative
      electrophoresis and 2-DE, followed by PMF. A total of 778 protein spots
      corresponding to 141 different gene products were identified. In comparison, 171
      spots corresponding to 44 unique proteins were identified in the unfractionated
      starting material. Among the proteins identified from the preparative
      electrophoresis were many of low abundance such as proteins involved in signal
      transduction. Furthermore, the median molecular mass of the identified proteins
      from the preparative electrophoresis was significantly lower in comparison to the
      proteins identified from the unfractionated starting material (39 886 Da versus
      71 317 Da, respectively). Concluding, application of this methodology provides a
      coherent analysis of the urine proteome and contributes to the generation of the
      urine protein map in health and disease.

PMID- 16807943
TI  - Proteomic signatures corresponding to histological classification and grading of
      soft-tissue sarcomas.
AB  - We performed a global protein expression study on soft-tissue sarcoma in order to
      develop novel diagnostic biomarkers and allow molecular classification. 2-D
      difference gel electrophoresis was used to generate the global protein expression
      profiles of 80 soft-tissue sarcoma samples with seven different histological
      backgrounds. We found that 67 protein spots distinguished the subtypes of soft
      tissue sarcoma. Hierarchical clustering with these 67 protein spots resulted in
      the grouping of all 80 sarcoma samples corresponding to the histological
      classification. We found that the expression pattern of tropomyosin isoforms was
      different in conventional and pleomorphic leiomyosarcomas. We also identified
      five proteins, including alpha-1-antitrypsin, alpha-actinin 1, HSP27, and
      elongation factor 2, that could differentiate between malignant fibrous
      histiocytomas and leiomyosarcomas in grade III into low-risk and high-risk
      groups, which differed significantly with respect to survival. These results
      establish proteomics as a powerful tool to develop novel biomarkers for diagnosis
      and molecular classification of soft-tissue sarcomas. Identification of proteins
      associated with survival in grade III sarcoma will allow delineation of a high
      risk group that may benefit from adjuvant therapy and the exclusion of low-risk
      patients in whom additional therapies are unlikely to exhibit clinical benefit.

PMID- 16807945
TI  - A triad based on an iridium(III) bisterpyridine complex leading to a charge
      separated state with a 120-micros lifetime at room temperature.
AB  - A triad D-Ir-A, where Ir is an Ir(III) bisterpyridine complex connected through
      an amidophenyl spacer to D, a triphenylamine electron donor, and to A, a
      naphthalene bisimide electron acceptor, has been synthesized and
      electrochemically investigated. The photoinduced processes in the triad, which is
      more than 4-nm long, have been characterized by steady-state and time-resolved
      optical spectroscopy by comparison with the model dyads D-Ir, Ir-A, and the
      reference monomers D, Ir, and A. A sequential electron transfer occurs upon
      excitation of the D and Ir units, leading to the charge-separated state D+-Ir- -A
      in 100 % yield and subsequently to D+-Ir-A- in about 10 % yield. The final charge
      separated state has a lifetime at room temperature of 120 micros in air-free
      acetonitrile and of 100 micros in air-equilibrated solvent. Excitation of the A
      units does not yield intramolecular reactivity, but the resulting triplet-excited
      state localized on the acceptor, D-Ir-3A, displays intermolecular reactivity.

PMID- 16807944
TI  - Impact of the availability of sonography in the acute gynecology unit.
AB  - OBJECTIVE: The initial assessment of acute gynecology patients is usually based
      on history and clinical examination and does not involve ultrasound. The aim of
      this study was to investigate the impact of the availability of transvaginal
      sonography at the time of initial assessment of the emergency gynecology patient.
      METHODS: This was a prospective observational study carried out over a 5-month
      period in the acute gynecology unit of an inner London teaching hospital. Women
      were assessed in the routine manner by history-taking and clinical examination
      and questionnaires were completed by the doctors, including details of the
      intention to treat. Transvaginal ultrasound examinations were then performed and
      a second diagnosis and management plan were made utilizing the extra information
      from the scan. The plans for clinical management before and after the ultrasound
      examination were compared. RESULTS: We originally recruited 1000 consecutive
      women to the study. The mean age was 31.1 (SD, 9.81) years. Complete data were
      available for 920 (92%). 84 (9.1%) women did not require a scan. Of the 521 women
      with a positive pregnancy test, 75.6% were reassured immediately that their
      pregnancy was intrauterine. 143 women (27.4%) were given the diagnosis of a
      suspected ectopic pregnancy before sonography, compared with 29 (5.6%) after.
      Following the ultrasound examination there was a change in clinical management in
      54.1% of the women with a positive pregnancy test and a reduction in admissions
      (including inpatient theater admissions) (from 40.3% to 17.1%) and outpatient
      follow-up examinations (from 41.1% to 35.5%). In 90 (23.8%) non-pregnant women a
      significant ovarian cyst (> 5 cm) was suspected clinically; 28/90 (31.1%) were
      confirmed on sonography. Following the ultrasound examination there was a change
      in clinical management for 38.1% of non-pregnant women and a reduction in
      admissions (from 37.1% to 19.4%) and outpatient follow-up examinations (from
      25.7% to 18.1%). CONCLUSION: It appears that the availability of transvaginal
      sonography at the time of initial assessment of emergency gynecology patients
      improves diagnostic accuracy and reduces unnecessary admissions and follow-up
      examinations.

PMID- 16807946
TI  - Host-guest chemistry of copper(II)-histidine complexes encaged in zeolite Y.
AB  - Structural analysis has been carried out on copper(II)-histidine (Cu(2+)/His)
      complexes after immobilization in the pore system of the zeolites NaY and de
      aluminated NaY (DAY). The aim of this study was to determine the geometrical
      structure of Cu(2+)/His complexes after encaging, to obtain insight into both the
      effect of the zeolite matrix on the molecular structure and redox properties of
      the immobilized complexes. In addition to N(2) physisorption and X-ray
      fluorescence (XRF) analyses, a combination of UV/Vis/NIR, ESR, X-ray absorption
      (EXAFS and XANES), IR, and Raman spectroscopy was used to obtain complementary
      information on both the first coordination shell of the copper ion and the
      orientation of the coordinating His ligands. It was demonstrated that two
      complexes (A and B) are formed, of which the absolute and relative abundance
      depends on the Cu(2+)/His concentration in the ion-exchange solution and on the
      Si/Al ratio of the zeolite material. In complex A, one His ligand coordinates in
      a tridentate facial-like manner through N(am), N(im), and O(c), a fourth position
      being occupied by an oxygen atom from a zeolite Bronsted site. In complex B, two
      His ligands coordinate as bidentate ligands; one histamine-like (N(am), N(im))
      and the other one glycine-like (N(am), O(c)). In particular the geometrical
      structure of complex A differs from the preferred structure of Cu(2+)/His
      complexes in aqueous solutions; this fact implies that the zeolite host material
      actively participates in the coordination and orientation of the guest molecules.
      The tendency for complex A to undergo reduction in inert atmosphere to Cu(1+) (as
      revealed by dynamic XANES studies) suggests activation of complex A by the
      interaction with the zeolite material. EXAFS analysis confirms the formation of a
      distorted four coordinate geometry of complex A, suggesting that the combination
      of zeolite and one His ligand force the Cu(2+) complex into an activated,
      entactic state.

PMID- 16807948
TI  - A hyaluronidase supercatalyst for the enzymatic polymerization to synthesize
      glycosaminoglycans.
AB  - Hyaluronidase (HAase) catalyzes multiple enzymatic polymerizations with
      controlling regio- and stereoselectivity perfectly. This behavior, that is, the
      single enzyme being effective for multireactions and retaining the enzyme
      catalytic specificity, is not usual, and hence, HAase is a supercatalyst. Various
      sugar oxazoline monomers prepared based on the concept "transition-state analogue
      substrate" were successfully polymerized and copolymerized with HAase catalysis,
      yielding natural and unnatural glycosaminoglycans.

PMID- 16807947
TI  - Lipopolysaccharides from Serratia marcescens possess one or two 4-amino-4-deoxy-L
      arabinopyranose 1-phosphate residues in the lipid A and D-glycero-D-talo-oct-2
      ulopyranosonic acid in the inner core region.
AB  - The carbohydrate backbones of the core-lipid A region were characterized from the
      lipopolysaccharides (LPSs) of Serratia marcescens strains 111R (a rough mutant
      strain of serotype O29) and IFO 3735 (a smooth strain not serologically
      characterized but possessing the O-chain structure of serotype O19). The LPSs
      were degraded either by mild hydrazinolysis (de-O-acylation) and hot 4 M KOH (de
      N-acylation), or by hydrolysis in 2 % aqueous acetic acid, or by deamination.
      Oligosaccharide phosphates were isolated by high-performance anion-exchange
      chromatography. Through the use of compositional analysis, electrospray
      ionization Fourier transform mass spectrometry, and 1H and 13C NMR spectroscopy
      applying various one- and two-dimensional experiments, we identified the
      structures of the carbohydrate backbones that contained D-glycero-D-talo-oct-2
      ulopyranosonic acid and 4-amino-4-deoxy-L-arabinose 1-phosphate residues. We also
      identified some truncated structures for both strains. All sugars were D
      configured pyranoses and alpha-linked, except where stated otherwise.

PMID- 16807950
TI  - Formation of complex micelles with double-responsive channels from self-assembly
      of two diblock copolymers.

PMID- 16807949
TI  - Palladium-catalyzed DYKAT of butadiene monoepoxide: enantioselective total
      synthesis of (+)-DMDP, (-)-bulgecinine, and (+)-broussonetine G.
AB  - Palladium catalyzed asymmetric allylic alkylation reaction of an amine with two
      equivalents of butadiene monoxide allows for the expedient synthesis of trans-
      and cis-2,5-dihydropyrroles. The versatility of these chiral synthons towards the
      synthesis of a wide variety of iminosugar natural products was demonstrated with
      the short and high yielding asymmetric syntheses of (+)-DMDP, and (-)
      bulgecinine. In addition, the first total synthesis of (+)-broussonetine G, a
      potent glycosidase inhibitor, is described along with the assignment of its
      relative and absolute stereochemical configuration.

PMID- 16807951
TI  - Metastable sorption state of a metal-organic porous material determined by in
      situ synchrotron powder diffraction.

PMID- 16807952
TI  - HaloTag protein-mediated site-specific conjugation of bioluminescent proteins to
      quantum dots.

PMID- 16807953
TI  - [Pd(Ar-BIAN)(alkene)]-catalyzed highly chemo-, regio-, and stereoselective
      semihydrogenation of 1,2-allenyl phosphonates and related compounds.

PMID- 16807954
TI  - Diagnosis and prognosis of fetuses with double outlet right ventricle.
AB  - OBJECTIVES: To examine the echocardiographic features, associated anomalies, and
      outcomes of fetuses diagnosed with double outlet right ventricle (DORV). METHODS:
      Fetuses with DORV were identified from 987 fetal echocardiograms performed from
      August 1, 2002 to August 1, 2004. The medical records of 19 fetuses with DORV
      were reviewed. RESULTS: Nineteen fetuses were diagnosed with DORV. The pregnancy
      was terminated in 15.8% (3/19) of cases. Postnatal assessment was not obtained in
      26.3% (5/19) cases. Accurate prenatal diagnosis of the relationship of the
      ventricular septal defect (VSD) with the great arteries was achieved in 14 of 14
      cases (100%). Chromosomal abnormalities (21.4%), abnormalities of body situs
      (35.7%), and other extracardiac abnormalities were diagnosed in association. Only
      4 of 13 (30.8%) infants with confirmed DORV survived beyond 28 days. CONCLUSIONS:
      DORV is found in fetuses with a large spectrum of associated cardiac and
      extracardiac lesions. The overall prognosis for fetuses with DORV is poor
      throughout the spectrum of these lesions, not only related to the primary lesion
      but also depending on the associated intra- and extracardiac abnormalities. While
      the complexity of the heart disease in fetuses with DORV makes detailed fetal
      diagnosis challenging, it can be accomplished with a high degree of accuracy.

PMID- 16807955
TI  - Optimising non-viral gene delivery in a tumour spheroid model.
AB  - BACKGROUND: Our current understanding of how the unique tumour microenvironment
      influences the efficacy of gene delivery is limited. The current investigation
      systematically examines the efficiency of several non-viral gene transfer agents
      to transfect multicellular tumour spheroids (MCTS), an in vitro model that
      displays a faithful three-dimensional (3D) representation of solid tumour tissue.
      METHODS: Using a luciferase reporter assay, gene transfer to MCTS was optimised
      for 22 kDa linear and 25 kDa branched polyethyleneimine (PEI), the cationic
      lipids Lipofectamine(trade mark) and DCChol : DOPE, and the physical approach of
      tissue electroporation. Confocal microscopy was used to take optical tissue
      slices to identify the tissue localisation of green fluorescent protein (GFP)
      reporter gene expression and the distribution of fluorescently labelled
      complexes. A MCTS model of quiescent tumour regions was used to establish the
      influence of cellular proliferation status on gene transfer efficiency. RESULTS:
      Of the polyplexes tested, 22 kDa linear PEI provided optimal gene delivery, with
      gene expression peaking at 46 h. Despite being the optimal vector tested, PEI
      mediated transfection was limited to cells at the MCTS periphery. Using
      fluorescent PEI, it was found that complexes could only penetrate the outer 3-5
      proliferating cell layers of the MCTS, sparing the deeper quiescent cells. Gene
      delivery in an MCTS model comprised entirely of quiescent cells demonstrated that
      in addition to being inaccessible to the vector, quiescent tumour regions are
      inherently less susceptible to PEI-mediated transfection than proliferating
      regions. This 'resistance' to transfection observed in quiescent cells was
      overcome through the use of electroporation. Despite the improved efficacy of
      electroporation in quiescent tissue, the gene expression was still confined to
      the outer regions of MCTS. The results suggest that limited access to central
      regions of an MCTS remain a significant barrier to gene delivery. CONCLUSIONS:
      This data provides new insights into tumour-specific factors affecting non-viral
      gene transfer and highlights the difficulties in delivering genes to avascular
      tumour regions. The MCTS model is a useful system for the initial screening of
      future gene therapy strategies for solid tumours.

PMID- 16807956
TI  - Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA, VII, and XIV
      with l- and d-histidine and crystallographic analysis of their adducts with
      isoform II: engineering proton-transfer processes within the active site of an
      enzyme.
AB  - Activation of six human carbonic anhydrases (CA, EC 4.2.1.1), that is, hCA I, II,
      IV, VA, VII, and XIV, with l- and d-histidine was investigated through kinetics
      and by X-ray crystallography. l-His was a potent activator of isozymes I, VA,
      VII, and XIV, and a weaker activator of hCA II and IV. d-His showed good hCA I,
      VA, and VII activation properties, being a moderate activator of hCA XIV and a
      weak activator of hCA II and IV. The structures as determined by X-ray
      crystallography of the hCA II-l-His/d-His adducts showed the activators to be
      anchored at the entrance of the active site, contributing to extended networks of
      hydrogen bonds with amino acid residues/water molecules present in the cavity,
      explaining their different potency and interaction patterns with various
      isozymes. The residues involved in l-His recognition were His64, Asn67, Gln92,
      whereas three water molecules connected the activator to the zinc-bound
      hydroxide. Only the imidazole moiety of l-His interacted with these amino acids.
      For the d-His adduct, the residues involved in recognition of the activator were
      Trp5, His64, and Pro201, whereas two water molecules connected the zinc-bound
      water to the activator. Only the COOH and NH(2) moieties of d-His participated in
      hydrogen bonds with these residues. This is the first study showing different
      binding modes of stereoisomeric activators within the hCA II active site, with
      consequences for overall proton-transfer processes (rate-determining for the
      catalytic cycle). The study also points out differences of activation efficiency
      between various isozymes with structurally related activators, convenient for
      designing alternative proton-transfer pathways, useful both for a better
      understanding of the catalytic mechanism and for obtaining pharmacologically
      useful derivatives, for example, for the management of Alzheimer's disease.

PMID- 16807957
TI  - Catalytic ethylene polymerisation in carbon dioxide as a reaction medium with
      soluble nickel(II) catalysts.
AB  - A series of neutral Ni(II)-salicylaldiminato complexes substituted with
      perfluorooctyl- and trifluoromethyl groups, [Ni{kappa(2)-N,O-6-C(H)==NAr-2,4
      R'(2)C(6)H(2)O}(Me)(pyridine)] (6 a: Ar=2,6-{4-(F(17)C(8))C(6)H(4)}(2)C(6)H(3),
      R'=I; 6 b: Ar=2,6-{4-(F(3)C)C(6)H(4)}(2)C(6)H(3), R'=I; 6 c: Ar=2,6-{3,5
      (F(3)C)(2)C(6)H(3)}(2)C(6)H(3), R'=3,5-(F(3)C)(2)C(6)H(3); 6 d: Ar=2,6-{4
      (F(17)C(8))C(6)H(4)}(2)C(6)H(3), R'=3,5-(F(3)C)(2)C(6)H(3); 6 e: Ar=2,6-{3,5
      (F(3)C)(2)C(6)H(3)}(2)C(6)H(3), R'=I) were studied as catalyst precursors for
      ethylene polymerisation in supercritical CO(2). Catalyst precursors 6 a and 6 c,
      which are soluble in scCO(2), afford the highest polymer yields, corresponding to
      2 x 10(3) turnovers. Semicrystalline polyethylene (M(n) typically 10(4) g mol(
      1)) is obtained with variable degrees of branching (11 to 24 branches per 1000
      carbon atoms, predominantly Me branches) and crystallinities (54 to 21 %),
      depending on the substitution pattern of the catalyst.

PMID- 16807958
TI  - Specific vectorial immobilization of oligonucleotide-modified yeast cytochrome C
      on carbon nanotubes.
AB  - Iso-1-cytochrome c from the yeast Saccharomyces cerevisiae (YCC) contains a
      surface cysteine residue, Cys102, that is located opposite to the lysine-rich
      side containing the exposed heme edge, which is the docking site for enzymes.
      Site-specific vectorial immobilization of YCC via Cys102 on single-walled carbon
      nanotubes (SWNT) thus provides a selective interface between nanoscopic
      electronic devices and complex enzymes. We have achieved this by modification of
      Cys102 with an oligonucleotide (dT(18)). Atomic force microscopy, fluorescence
      imaging, and cyclic voltammetry show the specific adsorption of YCC, modified
      with dT(18), on the SWNT sidewall with retention of its native properties.
      Pretreatment of the SWNT with Triton-X405 blocks the nonspecific binding of
      untreated YCC but does not interfere with binding of the oligonucleotide-modified
      YCC.

PMID- 16807959
TI  - Molecular-recognition and binding properties of cyclodextrin-conjugated
      polyrotaxanes.

PMID- 16807960
TI  - Surface composition of materials used as catalysts for methanol steam reforming:
      a theoretical study.
AB  - PdZn (1:1) alloy is assumed to be the active component of a promising catalyst
      for methanol steam reforming. Using density functional calculations on periodic
      supercell slab models, followed by atomistic thermodynamics modeling, we study
      the chemical composition of the surfaces PdZn(111) and, as a reference, Cu(111)
      in contact with water and hydrogen at conditions relevant to methanol steam
      reforming. For the two surfaces, we determine similar maximum adsorption energies
      for the dissociative adsorption of H(2), O(2), and the molecular adsorption of
      H(2)O. These reactions are calculated to be exothermic by about -40, -320, and 
      20 kJ mol(-1), respectively. Using a thermodynamic analysis based on
      theoretically predicted adsorption energies and vibrational frequencies, we
      determine the most favorable surface compositions for given pressure windows.
      However, surface energy plots alone cannot provide quantitative information on
      individual coverages in a system of coupled adsorption reactions. To overcome
      this limitation, we employ a kinetic model, from which equilibrium surface
      coverages of H, O, OH, and H(2)O are derived. We also discuss the sensitivity of
      our results and the ensuing conclusions with regard to the model surfaces
      employed and the inaccuracies of our computational method. Our kinetic model
      predicts surfaces of both materials, PdZn and Cu, to be essentially adsorbate
      free already from very low values of the partial pressure of H(2). The model
      surfaces PdZn(111) and Cu(111) are predicted to be free of water-related
      adsorbates for a partial H(2) pressure greater than 10(-8) and 10(-5) atm,
      respectively.

PMID- 16807961
TI  - Discovery of a family of isopolyoxotungstates [H4W19O62]6- encapsulating a {WO6}
      moiety within a {W18} Dawson-like cluster cage.

PMID- 16807962
TI  - Chemical locomotion.
AB  - Research into the autonomous motion of artificial nano- and microscale objects
      provides basic principles to explore possible applications, such as self-assembly
      of superstructures, roving sensors, and drug delivery. Although the systems
      described have unique propulsion mechanisms, motility in each case is made
      possible by the conversion of locally available chemical energy into mechanical
      energy. The use of catalysts onboard can afford nondissipative systems that are
      capable of directed motion. Key to the design of nano- and micromotors is the
      asymmetric placement of the catalyst: its placement in an environment containing
      a suitable substrate translates into non-uniform consumption of the substrate and
      distribution of reaction products, which results in the motility of the object.
      These same principles are exploited in nature to effect autonomous motion.

PMID- 16807963
TI  - Enhancement of Pt utilization in electrocatalysts by using gold nanoparticles.

PMID- 16807964
TI  - A unique mechanism for methyl ester formation via an amide intermediate found in
      myxobacteria.
AB  - Secondary metabolism involves a broad diversity of biochemical reactions that
      result in a wide variety of biologically active compounds. Terminal amide
      formation during the biosynthesis of the myxobacterial electron-transport
      inhibitor, myxothiazol, was analyzed by heterologous expression of the unique
      nonribosomal-peptide synthetase, MtaG, and incubation with a synthesized
      substrate mimic. These experiments provide evidence that the terminal amide is
      formed from a carrier protein-bound myxothiazol acid that is thioesterified to
      MtaF. This intermediate is transformed to an amide by extension with glycine and
      subsequent oxidative cleavage by MtaG. The final steps of melithiazol assembly
      involve a highly similar protein-bound intermediate (attached to MelF, a
      homologue of MtaF), which is transformed to an amide by MelG (homologue of MtaG).
      In this study, we also show that the amide moiety of myxothiazol A can be
      hydrolyzed in vivo to the formerly unknown free myxothiazol acid by heterologous
      expression of melJ in the myxothiazol producer Stigmatella aurantiaca DW4/3-1.
      The methyltransferase MelK can finally methylate the acid to give rise to the
      methyl ester, which is produced as the final product in the melithiazol A
      biosynthetic pathway. These experiments clarify the role of MelJ and MelK during
      melithiazol assembly.

PMID- 16807965
TI  - Long-lived palladium catalysts for CO/vinyl arene polyketones synthesis: a
      solution to deactivation problems.
AB  - A series of cationic palladium complexes of general formula [Pd(Me)(MeCN)(N
      N)][PF(6)] (N-N = (phen) 1 a, 4,7-dichloro-1,10-phenanthroline (4,7-Cl(2)-phen) 2
      a, 4,7-diphenyl-1,10-phenanthroline (4,7-Ph(2)-phen) 3 a, 4-methyl-1,10
      phenanthroline (4-Me-phen) 4 a, 4,7-dimethyl-1,10-phenanthroline (4,7-Me(2)-phen)
      5 a, 5,5,6,6-tetrafluoro-5,6-dihydro-1,10-phenanthroline (F(4)-phen) 6 a,
      containing different substituted phenanthroline ligands, have been prepared from
      the corresponding neutral chloro derivatives [Pd(Me)(Cl)(N-N)], (1 b-6 b). The X
      ray crystal structure of [Pd(Cl)(2)(4,7-Cl(2)-phen)] (2 b') was determined. DFT
      calculations show that the electron density on the metal is tuned by the
      substituents on the ligands. The catalytic behavior of complexes 1 a-6 a in the
      CO/styrene and CO/p-Me-styrene copolymerizations was studied in detail, showing
      that the generated catalysts are active for at least 90 h, yielding copolymers of
      high molecular weight. A firm correlation between the electron density on
      palladium on the one hand and the catalytic activity of the complexes and the
      molecular weight and the stereochemistry of the polyketones synthesized on the
      other hand has been established: the catalyst containing the F(4)-phen is thus
      far the most active among those tested, yielding the syndiotactic CO/styrene
      copolymer with a stereoregularity of 96 % (uu triad) and with an M(w) value of 1
      000 000.

PMID- 16807966
TI  - Significantly accelerated direct electron-transfer kinetics of hemoglobin in a
      C(60)-MWCNT nanocomposite film.
AB  - The direct electrochemistry of hemoglobin (Hb) was studied in a novel all-carbon
      nanocomposite film of C(60)-MWCNT (MWCNT=multiple-walled carbon nanotube) and
      compared with that in bare MWCNT film. The heterogeneous electron-transfer rate
      constant k(s) of Hb/C(60)-MWCNT was determined to be 0.39 s(-1), which is more
      than one order of magnitude greater than that of Hb/MWCNT (0.03 s(-1)). The
      significantly accelerated electron-transfer kinetics are attributed to the
      mediator role played by C(60), which is finely dispersed on the MWCNT surfaces.
      The excellent stability of Hb/C(60)-MWCNT was established and its potential
      application towards the electrocatalytic reduction of O(2) was demonstrated.

PMID- 16807967
TI  - Ruthenation of duplex and single-stranded d(CGGCCG) by organometallic anticancer
      complexes.
AB  - We have studied the interaction of the organometallic anticancer ruthenium(II)
      complexes [(eta(6)-p-cymene)Ru(en)Cl][PF(6)] (1) and [(eta(6)
      biphenyl)Ru(en)Cl][PF(6)] (2) (en=ethylenediamine) with the single-stranded (ss)
      DNA hexamer d(CGGCCG) (I) and the duplex d(CGGCCG)(2) (II) by HPLC, ESI-MS, and
      one- and two-dimensional (1)H and (15)N NMR spectroscopy. For ss-DNA, all three
      G's are readily ruthenated with [(eta(6)-arene)Ru(en)](2+), but for duplex DNA
      there is preferential ruthenation of G3 and G6, and no binding to G2 was
      detected. For monoruthenated duplexes, N7 ruthenation of G is accompanied by
      strong hydrogen bonding between G-O6 and en-NH for the p-cymene adducts.
      Intercalation of the non-coordinated phenyl ring between G3 and C4 or G6 and C5
      was detected in the biphenyl adducts of mono- and diruthenated duplexes, together
      with weakening of the G-O6NH-en hydrogen bonding. The arene ligand plays a major
      role in distorting the duplex either through steric interactions (p-cymene) or
      through intercalation (biphenyl).

PMID- 16807968
TI  - Resonance structures of the amide bond: the advantages of planarity.
AB  - Delocalization indexes based on magnitudes derived from electron-pair densities
      are demonstrated to be useful indicators of electron resonance in amides. These
      indexes, based on the integration of the two-electron density matrix over the
      atomic basins defined through the zero-flux condition, have been calculated for a
      series of amides at the B3LYP/6-31+G* level of theory. These quantities, which
      can be viewed as a measure of the sharing of electrons between atoms, behave in
      concordance with the traditional resonance model, even though they are integrated
      in Bader atomic basins. Thus, the use of these quantities overcomes contradictory
      results from analyses of atomic charges, yet keeps the theoretical appeal of
      using nonarbitrary atomic partitions and unambiguously defined functions such as
      densities and pair densities. Moreover, for a large data set consisting of 24
      amides plus their corresponding rotational transition states, a linear relation
      was found between the rotational barrier for the amide and the delocalization
      index between the nitrogen and oxygen atoms, indicating that this parameter can
      be used as an ideal physical-chemical indicator of the electron resonance in
      amides.

PMID- 16807969
TI  - Characterising the electronic structure of ionic liquids: an examination of the 1
      butyl-3-methylimidazolium chloride ion pair.
AB  - In this paper we analyse the electronic properties of gas-phase 1-butyl-3
      methylimidazolium Cl ion pairs, [C(4)C(1)im]Cl, in order to deepen our
      understanding of ionic liquids in general. Examination of charge densities,
      natural bond orbitals (NBO), and delocalised molecular orbitals computed at the
      B3LYP and MP2/6-31(++)G(d,p) levels have enabled us to explain a number of
      experimental phenomena: the relative acidity of different sites on the
      imidazolium ring, variations in hydrogen-bond donor and acceptor abilities, the
      apparent contradiction of the hydrogen-bond-donor parameters for different types
      of solute, the low probability of finding a Cl(-) anion at the rear of the
      imidazolium ring and the expansion of the imidazolium ring in the presence of a
      strong hydrogen-bond acceptor. The unreactive but coordinating environment and
      large electrochemical window have also been accounted for, as has the strong
      electron-donating character of the carbon atoms to the rear of the ring in
      associated imidazolylidenes. The electronic structure of the [C(4)C(1)im](+)
      cation is best described by a C(4)==C(5) double bond at the rear, and a
      delocalised three-centre 4 e(-) component across the front (N(1)-C(2)-N(3)) of
      the imidazolium ring; delocalisation between these regions is also significant.
      Hydrogen-bond formation is driven by Coulombic stabilisation, which compensates
      for an associated destabilisation of the electronic part of the system.
      Interactions are dominated by a large positive charge at C(2) and the build up of
      pi-electron density above and below the ring, particularly that associated with
      the double bond between C(4) and C(5). The NBO partial charges have been computed
      and compared with those used in a number of classical simulations.

PMID- 16807970
TI  - An experimental and theoretical investigation of gas-phase reactions of Ca2+ with
      glycine.
AB  - The gas-phase reactions between Ca(2+) and glycine ([Ca(gly)](2+)) have been
      investigated through the use of mass spectrometry techniques and B3-LYP/cc-pWCVTZ
      density functional theory computations. The major peaks observed in the
      electrospray MS/MS spectrum of [Ca(gly)](2+) correspond to the formation of the
      [Ca,C,O(2),H](+), NH(2)CH(2) (+), CaOH(+), and NH(2)CH(2)CO(+) fragment ions,
      which are produced in Coulomb explosion processes. The computed potential energy
      surface (PES) shows that not only are these species the most stable product ions
      from a thermodynamic point of view, but they may be produced with barriers lower
      than for competing processes. Carbon monoxide is a secondary product, derived
      from the unimolecular decomposition of some of the primary ions formed in the
      Coulomb explosions. In contrast to what is found for the reactions of Ca(2+) with
      urea ([Ca(urea)](2+)), minimal unimolecular losses of neutral fragments are
      observed for the gas-phase fragmentation processes of [Ca(gly)](2+), which is
      readily explained in terms of the topological differences between their
      respective PESs.

PMID- 16807971
TI  - Diels-Alder ligation of peptides and proteins.
AB  - The development of the Diels-Alder cycloaddition as a new method for the site
      specific chemoselective ligation of peptides and proteins under mild conditions
      is reported. Peptides equipped with a 2,4-hexadienyl ester and an N-terminal
      maleimide react in aqueous media to give cycloadducts in high yields and
      depending on the amino acid sequence with high stereoselectivity. Except for the
      cysteine SH group the transformation is compatible with all amino acid side chain
      functional groups. For ligation to proteins the hexadienyl group was attached to
      avidin and streptavidin noncovalently by means of complex formation with a
      biotinylated peptide or by covalent attachment of a hexadienyl ester-containing
      label to lysine side chains incorporated into the proteins. Site-specific
      attachment of the hexadienyl unit into a Rab protein was achieved by means of
      expressed protein ligation followed by protection of the generated cysteine SH by
      means of Ellman's reagent. The protein reacted with different maleimido-modified
      peptides under mild conditions to give the fully functional cycloadducts in high
      yield. The results demonstrate that the Diels-Alder ligation offers an
      advantageous and technically straightforward new opportunity for the site
      specific equipment of peptides and proteins with further functional groups and
      labels. It proceeds under very mild conditions and is compatible with most
      functional groups found in proteins. Its combination with other ligation methods,
      in particular expressed protein ligation is feasible.

PMID- 16807972
TI  - A DFT study on the relative affinity for oxygen of the alpha and beta subunits of
      hemoglobin.
AB  - DFT calculations are carried out on computational models of the active center of
      the alpha and beta subunits of hemoglobin in both its oxygenated (R) and
      deoxygenated (T) states. The computational models are defined by the full heme
      group, including all porphyrin substituents, and the four amino acids closer to
      it. The role of the protein environment is introduced by freezing the position of
      the alpha carbon atom of each of the four amino acids to the positions they have
      in the available PDB structures. Oxygen affinity is then evaluated by computing
      the energy difference between the optimized structures of the oxygenated and
      deoxygenated forms of each model. The results indicate a higher affinity of the
      alpha subunits over the beta ones. Analysis of the computed structures points out
      to the strength of the hydrogen bond between the distal histidine and the oxygen
      molecule as a key factor in discriminating the different systems.

PMID- 16807973
TI  - QM/MM calculations with DFT for taking into account protein effects on the EPR
      and optical spectra of metalloproteins. Plastocyanin as a case study.
AB  - A detailed study of the influence of the surrounding protein on magnetic and
      optical spectra of metalloproteins is presented using the quantum
      mechanical/molecular mechanical (QM/MM) approach. The well-studied type I copper
      site in plastocyanin in the cupric oxidation state is taken as a test case
      because its spectroscopic properties have been extensively studied and are well
      understood. The calculations have been performed using nonrelativistic and scalar
      relativistic (at the level of the zeroth order regular approximation, ZORA)
      calculations (B3LYP functional). Linear response theory has been used to
      calculate first- and second-order properties, namely the EPR g-tensor, the
      central metal hyperfine couplings (HFCs), the HFCs of the directly coordinating
      ligands, as well as superhyperfine couplings (1H, 14N) from remote nuclei,
      transition energies, and oscillator strengths. Two different model systems have
      been defined that do not and do include important amino acids from the second
      coordination sphere, respectively. For comparison, calculations have been carried
      out in the gas phase and in a dielectric continuum (conductor like screening
      model, COSMO) with a dielectric constant of four. The best results were obtained
      at the scalar relativistic ZORA level for the largest model in conjunction with
      explicit modeling of the protein environment through the QM/MM procedure, which
      is also considered to be the highest level of theory used in this work. The
      protein effects beyond the second coordination sphere were found to be quite
      substantial (up to 30% changes on some properties), and were found to require an
      explicit treatment of the protein beyond the second coordination sphere. In
      addition, the embedding water cage was found to have a nonnegligible influence on
      the calculated spectroscopic data, which is of the same order as the influence of
      the protein backbone charges. However, while qualitatively satisfactory, the
      errors in the calculated spectroscopic parameters are still substantial, and can
      all be traced back to the fact that the linear-response of the presently
      available functionals is "too stiff" with respect to the external perturbations
      at least for the model systems studied here. Ligand field-based approaches are
      used to correct for systematic errors in the DFT procedures. As a consequence, we
      propose a new breakdown of the copper hyperfine interaction into Fermi-contact,
      spin-dipolar and spin-orbit contributions.

PMID- 16807974
TI  - Metal-thiolate bonds in bioinorganic chemistry.
AB  - Metal-thiolate active sites play major roles in bioinorganic chemistry. The M-
      S(thiolate) bonds can be very covalent, and involve different orbital
      interactions. Spectroscopic features of these active sites (intense, low-energy
      charge transfer transitions) reflect the high covalency of the M--S(thiolate)
      bonds. The energy of the metal-thiolate bond is fairly insensitive to its
      ionic/covalent and pi/sigma nature as increasing M--S covalency reduces the
      charge distribution, hence the ionic term, and these contributions can
      compensate. Thus, trends observed in stability constants (i.e., the Irving
      Williams series) mostly reflect the dominantly ionic contribution to bonding of
      the innocent ligand being replaced by the thiolate. Due to high effective nuclear
      charges of the Cu(II) and Fe(III) ions, the cupric- and ferric-thiolate bonds are
      very covalent, with the former having strong pi and the latter having more sigma
      character. For the blue copper site, the high pi covalency couples the metal ion
      into the protein for rapid directional long range electron transfer. For
      rubredoxins, because the redox active molecular orbital is pi in nature, electron
      transfer tends to be more localized in the vicinity of the active site. Although
      the energy of hydrogen bonding of the protein environment to the thiolate ligands
      tends to be fairly small, H-bonding can significantly affect the covalency of the
      metal-thiolate bond and contribute to redox tuning by the protein environment.

PMID- 16807975
TI  - Performance of DFT in modeling electronic and structural properties of
      cobalamins.
AB  - Computational modeling of the enzymatic activity of B12-dependent enzymes
      requires a detailed understanding of the factors that influence the strength of
      the Co--C bond and the limits associated with a particular level of theory. To
      address this issue, a systematic analysis of the electronic and structural
      properties of coenzyme B12 models has been performed to establish the performance
      of three different functionals including B3LYP, BP86, and revPBE. In particular
      the cobalt-carbon bond dissociation energies, axial bond lengths, and selected
      stretching frequencies have been analyzed in detail. Current analysis shows that
      widely used B3LYP functional significantly underestimates the strength of the Co-
      C bond while the nonhybrid BP86 functional produces very consistent results in
      comparison to experimental data. To explain such different performance of these
      functionals molecular orbital analysis associated with axial bonds has been
      performed to show differences in axial bonding provided by hybrid and nonhybrid
      functionals.

PMID- 16807976
TI  - Correlation between computed gas-phase and experimentally determined solution
      phase infrared spectra: models of the iron-iron hydrogenase enzyme active site.
AB  - Gas-phase density functional theory calculations (B3LYP, double zeta plus
      polarization basis sets) are used to predict the solution-phase infrared spectra
      for a series of CO- and CN-containing iron complexes. It is shown that simple
      linear scaling of the computed C--O and C--N stretching frequencies yields
      accurate predictions of the the experimentally determined nu(CO) and nu(CN)
      values for a variety of complexes of different charges and in solvents of varying
      polarity. As examples of the technique, the resulting correlation is used to
      assign structures to spectroscopically observed but structurally ambiguous
      species in two different systems. For the (mu-SCH2CH2CH2S)[Fe(CO)3]2 complex in
      tetrahydrofuran solution, our calculations show that the initial electrochemical
      reduction process leads to a simple one-electron reduced product with a structure
      very similar to the (mu-SCH2CH2CH2S)[Fe(CO)3]2 parent complex. For the iron-iron
      hydrogenase enzyme active site, our computations show that the absence or
      presence of a water molecule near the distal iron center (the iron center further
      from the [4Fe4S] cluster and protein backbone) has very little effect on the
      predicted infrared spectra.

PMID- 16807977
TI  - An update of the defensive barrier function of skin.
AB  - Skin, as the outermost organ in the human body, continuously confronts the
      external environment and serves as a primary defense system. The protective
      functions of skin include UV-protection, anti-oxidant and antimicrobial
      functions. In addition to these protections, skin also acts as a sensory organ
      and the primary regulator of body temperature. Within these important functions,
      the epidermal permeability barrier, which controls the transcutaneous movement of
      water and other electrolytes, is probably the most important. This permeability
      barrier resides in the stratum corneum, a resilient layer composed of corneocytes
      and stratum corneum intercellular lipids. Since the first realization of the
      structural and biochemical diversities involved in the stratum corneum, a
      tremendous amount of work has been performed to elucidate its roles and functions
      in the skin, and in humans in general. The perturbation of the epidermal
      permeability barrier, previously speculated to be just a symptom involved in skin
      diseases, is currently considered to be a primary pathophysiologic factor for
      many skin diseases. In addition, much of the evidence provides support for the
      idea that various protective functions in the skin are closely related or even co
      regulated. In this review, the recent achievements of skin researchers focusing
      on the functions of the epidermal permeability barrier and their importance in
      skin disease, such as atopic dermatitis and psoriasis, are introduced.

PMID- 16807978
TI  - Pulmonary rehabilitation in patients with neuromuscular disease.
AB  - In neuromuscular disease (NMD) patients with progressive muscle weakness,
      respiratory muscles are also affected and hypercapnia can increase gradually as
      the disease progresses. The fundamental respiratory problems NMD patients
      experience are decreased alveolar ventilation and coughing ability. For these
      reasons, it is necessary to precisely evaluate pulmonary function to provide the
      proper inspiratory and expiratory muscle aids in order to maintain adequate
      respiratory function. As inspiratory muscle weakening progresses, NMD patients
      experience hypoventilation. At this point, respiratory support by mechanical
      ventilator should be initiated to relieve respiratory distress symptoms. Patients
      with adequate bulbar muscle strength and cognitive function who use a non
      invasive ventilation aid, via a mouthpiece or a nasal mask, may have their
      hypercapnia and associated symptoms resolved. For a proper cough assist, it is
      necessary to provide additional insufflation to patients with inspiratory muscle
      weakness before using abdominal thrust. Another effective method for managing
      airway secretions is a device that performs mechanical insufflation-exsufflation.
      In conclusion, application of non-invasive respiratory aids, taking into
      consideration characterization of respiratory pathophysiology, have made it
      possible to maintain a better quality of life in addition to prolonging the life
      span of patients with NMD.

PMID- 16807979
TI  - Effects of metoclopramide and ranitidine on preoperative gastric contents in day
      case surgery.
AB  - This prospective, randomized, double-blinded study was performed to evaluate the
      effects of intravenous metoclopramide and ranitidine on preoperative gastric
      contents in outpatients receiving intravenous anesthesia for laparoscopic
      gynecologic surgery. Fifteen minutes before the induction of anesthesia, the Z-M
      group (n=20) received 50 mg ranitidine and 10 mg metoclopramide intravenously and
      the control group (n=20) received the same volume of normal saline. Before the
      surgery, a 14-F multiorifice nasogastric tube was inserted to aspirate the
      gastric contents of patients under sedation with propofol and midazolam. The mean
      pH values of the gastric fluid were 2.7 +/- 2.0 (SD) [median 1.6 (range: 1.2
      7.2)] in the control group, and 6.1 +/- 1.9 [median 6.8 (range 1.4-7.8)] in the Z
      M group. The mean aspirated volumes (mL) were 15.3 +/- 10.4 (SD) [median 11.0
      (range: 5.0-44.0)] in the control group, and 6.9 +/- 10.0 (SD) [median 4.5
      (range: 0-38.0)] in the Z-M group. There were significantly more high-risk
      (gastric fluid volumes > 25 mL and pH < 2.5) patients in the control group (4/20,
      20%) than in the Z-M group (1/20, 5%). In conclusion, intravenous prophylactic
      ranitidine and metoclopramide may be an easy and useful method to decrease the
      volume while increasing the pH of gastric contents, and therefore may reduce the
      number of patients at risk for aspiration pneumonitis in ambulatory laparoscopic
      procedures who receive an anesthesia.

PMID- 16807980
TI  - Posterior lumbar interbody fusion via a unilateral approach.
AB  - This study sought to determine the outcomes of posterior lumbar interbody fusion
      (PLIF), via a unilateral approach, in selected patients who presented with
      unilateral leg pain and segmental instability of the lumbar spine. Patients with
      a single level of a herniated disc disease in the lumbar spine, unilateral leg
      pain, chronic disabling lower back pain (LBP), and a failed conservative
      treatment, were considered for the procedure. A total of 41 patients underwent a
      single-level PLIF using two PEEK (Poly-Ether-Ether-Ketone) cages filled with
      iliac bone, via a unilateral approach. The patients comprised 21 women and 20 men
      with a mean age of 41 years (range: 22 to 63 years). Two cages were inserted
      using a unilateral medial facetectomy and a partial hemilaminectomy. At follow
      up, the outcomes were assessed using the Prolo Scale. The success of the fusion
      was determined by dynamic lumbar radiography and/or computerized tomography
      scanning. All the patients safely underwent surgery without severe complications.
      During a mean follow-up period of 26 months, 1 patient underwent percutaneous
      pedicle screw fixation due to persistent LBP. A posterior displacement of the
      cage was found in one patient. At the last follow up, 90% of the patients
      demonstrated satisfactory results. An osseous fusion was present in 85% of the
      patients. A PLIF, via a unilateral approach, enables a solid union with
      satisfactory clinical results. This preserves part of the posterior elements of
      the lumbar spine in selected patients with single level instability and
      unilateral leg pain.

PMID- 16807981
TI  - Postoperative spinal epidural hematoma: risk factor and clinical outcome.
AB  - We report a series of epidural hematomas which cause neurologic deterioration
      after spinal surgery, and have taken risk factors and prognostic factors into
      consideration. We retrospectively reviewed the database of 3720 cases of spine
      operation in a single institute over 7 years (1998 April- 2005 July). Nine
      patients who demonstrated neurologic deterioration after surgery and required
      surgical decompression were identified. Factors postulated to increase the
      postoperative epidural hematoma and to improve neurologic outcome were
      investigated. The incidence of postoperative epidural hematoma was 0.24%.
      Operation sites were cervical 3 cases, thoracic 2 cases, and lumbar 4 cases.
      Their original diagnoses were tumor 3 cases, cervical stenosis 2 cases, lumbar
      stenosis 3 cases and herniated lumbar disc 1 case. The symptoms of epidural
      hematomas were neurologic deterioration and pain. After decompression, clinical
      outcome revealed complete recovery in 3 cases (33.3%), incomplete recovery in 5
      cases (55.6%) and no change in 1 case (11.1%). Factors increasing the risk of
      postoperative epidural hematoma were coagulopathy from medical illness or
      anticoagulation therapy (4 cases, 44.4%) and highly vascularized tumor (3 cases,
      33.3%). The time interval to evacuation of complete recovery group (29.3 hours)
      was shorter than incomplete recovery group (66.3 hours). Patients with
      coagulopathy and highly vascularized tumor were more vulnerable to spinal
      epidural hematoma. The postoperative outcome was related to the preoperative
      neurological deficit and the time interval to the decompression.

PMID- 16807982
TI  - Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ
      and invasive ductal carcinoma of the breast.
AB  - We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2
      mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive
      ductal carcinoma of the breast. We further compared these two types of carcinomas
      for differences in microvessel density, and expression of angiogenic factors and
      CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and
      invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2
      mRNAs were not statistically different between DCIS and invasive ductal
      carcinomas, nor did they differ statistically when grouped by tumor size,
      histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel
      density and expression of VEGF and TGF-beta1 were not statistically different
      between DCIS and invasive ductal carcinoma. CD44std expression was significantly
      increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was
      also significantly increased in lower clinical stage, histologic grade and
      nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis
      was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta1 expression (p
      < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2
      mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive
      ductal carcinoma suggest that the invasive potential of breast carcinoma is
      already achieved before morphologically overt invasive growth is observed. As MT1
      MMP mRNA expression is significantly correlated with axillary nodal metastasis,
      it may be useful as a prognostic indicator of invasive ductal carcinoma.
      Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression,
      our finding supports a role for TIMP2 in tumor growth, as well as the utility of
      CD44std as a prognostic indicator of breast cancer.

PMID- 16807983
TI  - Greater impairment in negative emotion evaluation ability in patients with
      paranoid schizophrenia.
AB  - To explore whether or not patients with schizophrenia display a more profound
      impairment of negative emotion processing, we assessed the implicit evaluation of
      positive and negative emotional stimuli. Twenty patients with schizophrenia (9
      paranoid, 11 non-paranoid) and 22 normal controls were instructed to classify
      emotional pictures according to the intrinsic valence if the pictures were black
      and white. If the stimuli were color-filtered, participants were instructed to
      press the positive/negative response key according to the extrinsic valence
      (assigned valence of color). The error rates of the color-filtered stimuli were
      used as dependent measures. Normal controls made more errors on trials of the
      positive pictures when the correct response was the negative response key than
      when the correct response was the positive response key. The reverse was true on
      trials of the negative pictures. Patients with schizophrenia, especially paranoid
      schizophrenia, committed more errors in trials of the positive pictures when the
      correct response key was the negative response key. However, the reverse was not
      true on trials of the negative pictures. These findings suggest that patients
      with paranoid schizophrenia might suffer from an impaired ability to evaluate
      negative emotions and have a loosening of association within their negative
      emotional networks.

PMID- 16807984
TI  - Human brain astrocytes mediate TRAIL-mediated apoptosis after treatment with IFN
      gamma.
AB  - TNF-related apoptosis inducing ligand (TRAIL) expressions were studied in primary
      human brain astrocytes in response to pro-inflammatory cytokines. When astrocytes
      were treated with IL-1beta, TNF-alpha or IFN-gamma, TRAIL was induced in cultured
      fetal astrocytes. In particular, IFN-gamma induced the highest levels of TRAIL in
      cultured astrocytes. When astrocytes were pre-treated with IFN-gamma, they
      induced apoptosis in TRAIL-sensitive Peer cells. Our results suggest that IFN
      gamma modulates the expression of TRAIL in astrocytes, which may enhance
      cytotoxic sensitivity of infiltrating immune cells or brain cells other than
      astrocytes during inflammation of brain.

PMID- 16807985
TI  - Antiallodynic effects of acupuncture in neuropathic rats.
AB  - Peripheral nerve injury often results in abnormal neuropathic pain such as
      allodynia or hyperalgesia. Acupuncture, a traditional Oriental medicine, has been
      used to relieve pain and related symptoms. However, the efficiency of acupuncture
      in relieving neuropathic pain is not clear. The aim of this study was to
      investigate the anti-allodynic effects of acupuncture through behavioral and
      electrophysiological examinations. Male Sprague-Dawley rats were subjected to
      neuropathic surgery consisting of a tight ligation and transection of the left
      tibial and sural nerves, under pentobarbital anesthesia. The acupuncture
      experiment consisted of four different groups, one treated at each of three
      different acupoints (Zusanli (ST36), Yinlingquan (SP9), and a sham-acupoint) and
      a control group. Behavioral tests for mechanical allodynia and cold allodynia
      were performed for up to two weeks postoperatively. Extracellular
      electrophysiological recordings were made from the dorsal roots using platinum
      wire electrodes. Mechanical and cold allodynia were significantly reduced after
      acupuncture treatment at the Zusanli and Yinlingquan acupoints, respectively.
      Electrophysiological neural responses to von Frey and acetone tests were also
      reduced after acupuncture at the same two acupoints. These results suggest that
      acupuncture may be beneficial in relieving neuropathic pain.

PMID- 16807986
TI  - Clinical experiences of cardiac myxoma.
AB  - Although cardiac myxoma is rare, it is the most common primary cardiac tumor.
      Seventy-four cases of cardiac myxoma that were surgically treated in our center
      between August 1980 and February 2005 were retrospectively reviewed. The mean
      patient age was 50.4 +/- 15.0 (range 7-80) years, and 53 patients (71.6%) were
      female. The most common preoperative symptom, occurring in 44 patients, was
      dyspnea. The interval from onset of symptoms to surgery was 9 months. Seventy
      cases were located in the left atrium, 3 in the right atrium and 1 in the right
      ventricle. The myxoma in the right ventricle could not be resected completely,
      due to severe infiltration. Cardiopulmonary bypass and aortic cross clamp times
      were 100.4 +/- 37.1 and 64.8 +/- 29.8 minutes, respectively. There were no
      hospital deaths, and 7 patients suffered from postoperative complications
      including atrial fibrillation in 2 cases. During the follow up period (mean 105.7
      +/- 73.6 months), there was no tumor recurrence and 6 late deaths that were not
      related to the underlying tumor. There was no evidence of tumor growth in the
      cases with incomplete resection during the 14-month follow-up. In conclusion, in
      this study there was no recurrence of tumors after complete resection and
      surgical resection is considered to be the curative method of treatment for
      cardiac myxoma.

PMID- 16807987
TI  - Analysis of C-reactive protein and biochemical parameters in pericardial fluid.
AB  - This study was designed to examine the relationship between pericardial fluid and
      plasma CRP levels, and to alterations in other biochemical parameters in patients
      undergoing Coronary Artery Bypass Grafting (CABG). The study group consisted of
      96 Coronary Artery Disease (CAD) patients who were referred to our clinic for a
      CABG procedure and from whom sufficient amount of pericardial fluid could be
      collected. The patients were classified into 3 groups: Stable Angina Pectoris
      (SAP) (n=27), Unstable Angina Pectoris (USAP) (n=36), and Post-Myocardial
      Infarction (PMI) (n=33). Levels of CRP, glucose, albumin, total protein, Creatine
      Kinase (CK), Creatine Kinase-MB (CK-MB), and Lactate Dehydrogenase (LDH) were
      determined in pericardial fluid samples and in simultaneously collected blood
      samples from radial artery. The pericardial CRP and LDH levels in the PMI group
      were higher than in the SAP (p=0.015 and p=0.000, respectively) and USAP
      (p=0.011, p=0.047) groups. Serum CRP levels in USAP (p=0.014) and PMI (p= 0.000)
      groups were higher than those in the SAP group. Pericardial albumin levels in the
      PMI group were higher than in the USAP group (p=0.038). In all groups, the
      pericardial fluid/serum protein ratio was > 0.5, the LDL ratio was > 0.6, and
      pericardial fluid LDH concentrations were > 300 mg/dl. CRP level of pericardial
      fluid was significantly higher in the PMI group than in other groups. However,
      pericardial fluid LDH levels were higher than blood LDH levels in this group and
      were also higher than pericardial fluid LDH levels of other groups.

PMID- 16807988
TI  - The effectiveness of embolotherapy for treatment of hemoptysis in patients with
      varying severity of tuberculosis by assessment of chest radiography.
AB  - The effectiveness of percutaneous embolotherapy in cases of hemoptysis due to
      pulmonary tuberculosis from increasing severity of lung parenchymal injury was
      compared. The pattern of pleural involvement, as seen on chest radiography and
      angiography, were comparatively analyzed in 230 patients who were available for
      follow-ups from March 1992 to December 2003. Chest radiography findings were
      classified into 4 types based on levels of complicated lesions and pleural
      involvement. Angiography findings were divided into 4 groups based on the level
      of blood supply to lesions. Early hemostasis with respect to radiographic group
      were as follows: Type I- 92% (73/79), Type II- 80% (52/65), Type III- 70%
      (42/60), and Type IV- 56% (52/92); there was an average success rate of 73%
      (219/296), and continued hemostasis was found in 80% of Type I patients (62/77),
      77% of Type II patients (41/53), 62% of Type III patients (25/40), and 45% of
      Type IV patients (27/60), with an average long- term hemostatic rate of 67%
      (155/230). Increasing severity of pleural involvement and associated
      complications correlated with increasing development of systemic collateral
      arteries other than the bronchial artery. The severely increased circulation in
      systemic collateral arteries makes it difficult to predict good hemostatic
      results following embolization. Therefore, we recommend aggressive treatment,
      such as surgical intervention, after embolization in such instances.

PMID- 16807989
TI  - Development of the stress-induced cognition scale.
AB  - The objective of this study was to develop the stress- induced cognition scale
      (SCS). A preliminary survey was conducted on 109 healthy adults to obtain
      cognitive stress responses. Then, 215 healthy subjects completed a preliminary
      questionnaire. A comparison was made regarding cognitive stress responses among
      73 patients with depressive disorders and 215 healthy subjects. Factor analysis
      of the SCS yielded 3 subscales: extreme thought, aggressive-hostile thought, and
      self-depreciative thought. The test-retest reliability for the 3 subscales and
      the total score was significantly high, ranging from 0.87 to 0.95. The Cronbach's
      alpha for the 3 subscales and total score ranged from 0.82 to 0.94. The
      convergent validity was calculated by correlating the 3 subscales and total score
      of the SCS with the total score of the global assessment of recent stress (GARS)
      scale, the perceived stress questionnaire (PSQ), and the Symptom Checklist-90
      Revised (SCL-90-R). The correlations were all at significant levels. The
      depressive disorder group scored significantly higher than the healthy control
      group in all the subscale scores and total scores of the SCS. Female subjects
      were significantly higher than males in the total scores of the SCS. These
      results indicate that the SCS is highly reliable and valid, and that it can be
      utilized as an effective measure for research related to cognitive assessment.

PMID- 16807990
TI  - Neonatal outcome after preterm delivery in HELLP syndrome.
AB  - The present study compares neonatal outcome after preterm delivery of infants in
      pregnancies complicated by the HELLP syndrome or severe preeclampsia (PS). The
      maternal and neonatal charts of 71 out of a total of 409 pregnancies that were
      complicated by hypertensive disorders at Severance hospital between January 1995
      and December 2004 were reviewed. Twenty-one pregnancies were complicated by HELLP
      syndrome and 50 pregnancies were complicated by PS. Fifty normotensive (NT)
      patients who delivered because of preterm labor comprised the control group.
      Results were analyzed by the chi-square test and ANOVA. Gestational age and
      maternal age at delivery were matched among the three groups. The neonatal
      outcomes of the HELLP syndrome group were compared with the PS and NT groups.
      There were significant differences between the HELLP syndrome group and the PS
      group in the incidence of intraventricular hemorrhage (IVH) (61.9% vs. 26%,
      p=0.006), sepsis (85.7% vs. 44%, p =0.003) and mechanical ventilation (MV) rate
      (81% vs. 54%, p=0.039). There were significant differences between the HELLP
      syndrome group and the NT group in the incidence of neonatal death (ND) (19.5%
      vs. 2.0%, p=0.034), respiratory distress syndrome (RDS) (38.1% vs. 8%, p=0.0045),
      IVH (61.9% vs. 4%, p < 0.0001), sepsis (85.7% vs. 14%, p < 0.0001), intensive
      care (IC) (85.7% vs. 24%, p < 0.0001) and MV rate (80.1% vs. 14%, p < 0.0001).
      There were also significant differences between the PS and NT groups in the
      incidence of ND (20% vs. 2%, p=0.0192), RDS (30% vs. 8%, p=0.0085), IVH (26% vs.
      4%, p=0.0070), sepsis (44% vs. 14%, p=0.0015), IC (78% vs. 24%, p < 0.0001), MV
      rate (54% vs. 14%, p < 0.0001) and low 5-min APGAR score (50% vs. 16%, p=0.0005).
      This study shows increased morbidity in newborns of mothers complicated with
      HELLP syndrome and indicates that early, regular and high quality management of
      these patients is essential to improve both maternal and neonatal outcome.

PMID- 16807991
TI  - Simplified EM grid vitrification is a convenient and efficient method for mouse
      mature oocyte cryopreservation.
AB  - This study was performed to evaluate the efficiency of simplified EM grid
      vitrification, skipping the step of removing the cryoprotectant (5.5M EG + 1.0M
      sucrose) droplet on the grid after loading oocytes, compared to conventional
      cryopreservation protocols for mouse mature oocytes. Firstly, the recovery,
      survival, fertilization and hatching rates of simplified EM grid vitrification
      were compared with those of the slow freezing method using 1.5M DMSO. Then,
      conventional EM grid vitrification was compared with simplified EM grid
      vitrification. Simplified EM grid vitrification showed higher survival,
      fertilization and hatching rates than those of the slow freezing method (85.6%
      vs. 63.2%; 51.0% vs. 22.3%; 38.7% vs. 12.5%, p < 0.01, respectively). Moreover,
      simplified EM grid vitrification showed higher recovery, survival and
      fertilization rates than those of conventional EM grid vitrification (100% vs.
      95.0%, p=0.024; 90.0% vs. 78.9%, p=0.033; 56.7% vs. 38.7%, p=0.021,
      respectively). Hatching rate tended to be higher for simplified EM grid
      vitrification compared to conventional EM grid vitrification (41.1% vs. 24.1%).
      In conclusion, simplified EM grid vitrification is a convenient and efficient
      method for cryopreservation of mouse mature oocytes, compared to conventional EM
      grid vitrification and slow freezing methods.

PMID- 16807992
TI  - Significance of small dense low-density lipoprotein as a risk factor for coronary
      artery disease and acute coronary syndrome.
AB  - Small dense LDL (sd-LDL) has recently emerged as an important coronary artery
      disease (CAD) risk factor. This study was performed to investigate how LDL
      particle size is related to CAD and acute coronary syndrome (ACS). Blood samples
      were collected from 504 patients that underwent coronary angiography to evaluate
      chest pain. The LDL particle size of these samples was measured. The mean LDL
      particle size was smaller in patients with angiographically proven CAD than in
      the controls (26.41 +/- 0.95 vs 26.73 +/- 0.64 nm, p < 0.001), and was negatively
      correlated with the Framingham risk score (r=-0.121, p=0.007). Patients with more
      extensive CAD had smaller LDL particles. LDL particle size was also smaller in
      patients with acute coronary syndrome as compared to non-ACS patients (26.09 +/-
      1.42 vs 26.54 +/- 0.63 nm, p=0.011). These results suggest that sd-LDL is
      independently associated with the incidence and extent of CAD, and can be a risk
      factor for the development of ACS in the Korean population.

PMID- 16807993
TI  - The relative contributions of the medial sural and peroneal communicating nerves
      to the sural nerve.
AB  - The medial sural cutaneous nerve (MSCN) and peroneal communicating nerve (PCN)
      conjoin in the calf area to form the sural nerve (SN). In previous anatomic
      studies, there was unresolved debate as to the main contributor to the sural
      nerve, and the relative contributions of MSCN and PCN had not been studied. The
      purpose of this study is to determine their relative neurophysiologic
      contributions to the SN by nerve conduction study (NCS). A total of 47 healthy
      subjects (25 males and 22 females, mean age 29.6 +/- 10.4 yrs, range 20-59 yrs)
      participated in the study. This study employed the orthodromic nerve conduction
      technique: stimulation at the ankle and recording at the mid calf (SN);
      specifically, we preformed stimulation at the mid calf (MSCN, PCN) and recording
      at 14 cm proximal to the middle of the popliteal fossa (MSCN) and fibular head
      (PCN). The onset and peak latencies (ms) were SN 2.3 +/- 0.2 and 3.0 +/- 0.2;
      MSCN 2.1 +/- 0.2 and 2.8 +/- 0.2; and PCN 2.1 +/- 0.2 and 2.8 +/- 0.2. The peak
      to-peak amplitudes (microV) and areas (nVsec) of the SN, MSCN, and PCN were 9.7
      +/- 3.9, 7.0 +/- 4.7, and 5.0 +/- 3.2; and 7.2 +/- 2.9, 5.7 +/- 3.4, and 4.0 +/-
      2.4, respectively. The side-to-side difference was not statistically significant.
      The main contributor to the SN was found to be the MSCN. The relative
      contribution ratio of the MSCN to the PCN was 1.37:1 by amplitude and 1.42:1 by
      area. However, in 32.9% of the subjects, the contribution of the PCN was greater
      than that of the MSCN.

PMID- 16807994
TI  - Treatment of infected urachal cysts.
AB  - The urachus is a fibrous cord that arises from the anterior bladder wall and
      extends cranially to the umbilicus. Traditionally, infection has been treated
      using a two-stage procedure that includes an initial incision and drainage which
      is then followed by elective excision. More recently, it has been suggested that
      a single-stage excision with improved antibiotics is a safe option. Thus, we
      intended to compare the effects of the two-stage procedure and the single-stage
      excision. We performed a retrospective review on nine patients treated between
      May 1990 and September 2005. The methods used in diagnosis were ultrasonography,
      computed tomography (CT), magnetic resonance imaging (MRI), and cystoscopy. The
      study group was comprised of three males and six females with a mean age of 28.2
      years (with a range from three to 71 years). Symptoms consisted of abdominal
      pain, abdominal mass, fever, and dysuria. The primary incision and drainage
      followed by a urachal remnant excision with a bladder cuff excision (two-stage
      procedure) was performed in four patients. The mean postoperative hospitalization
      lasted 5.8 days (with a range of three to seven days), and there were no reported
      complications. A primary excision of the infected urachal cyst and bladder cuff
      (single-stage excision) was performed in the other five patients. These patients
      had a mean postoperative hospitalization time of 9.2 days (with a range of four
      to 15 days), and complications included an enterocutaneous fistula, which
      required additional operative treatment. The best method of treating an infected
      urachal cyst remains a matter of debate. However, based on our results, the two
      stage procedure is associated with a shorter hospital stay and no complications.
      Thus, when infection is extensive and severe, we suggest that the two-stage
      procedure offers a more effective treatment option.

PMID- 16807995
TI  - An unusual case with membranous lipodystrophy in a hypertensive patient with
      transepidermal elimination.
AB  - Membranous lipodystrophy represents a peculiar type of fat necrosis that is
      present in patients with various types of skin disease. It is characterized by
      the presence of microcysts and macrocysts and is lined by amorphous eosinophilic
      material with a crenelated arabesque appearance. These findings have been
      associated with lupus erythematosus, diabetes mellitus, erythema nodosum, trauma,
      etc. We report a case of a 43-year-old woman who had a red to purple asymptomatic
      indurated plaque, approximately seven cm in diameter and on the left arm. She was
      a chronic hepatitis B antigen carrier and had hypertension for four years.
      Histopathology of the biopsied lesion showed transepidermal elimination of
      altered collagen and elastic fibers, as well as membranous lipodystrophy changes.
      There were hypertensive vascular changes including lymphohistiocytic infiltration
      around the vascular wall, swelling of endothelial cells, increased thickness of
      the vascular walls, and narrowing of the lumen. We report a case showing
      transepidermal elimination with membranous lipodystrophy. We carefully suggest
      that the secondary phenomenon of transepidermal elimination was associated with
      membranous lipodystrophy and degenerate connective tissues.

PMID- 16807996
TI  - A 20-year-old woman with Hashimoto's thyroiditis and Evans' syndrome.
AB  - Here we report the case of a 20-year-old female patient previously diagnosed with
      Hashimoto's thyroiditis and overt hypothyroidism, and who had been taking
      synthetic thyroxine (100 microg/day) for eight months. She experienced
      intermittent dizziness and generalized weakness, and was diagnosed as having
      severe autoimmune hemolytic anemia (AIHA). We prescribed prednisolone treatment
      and continued synthetic thyroxine administration. Two years and five months
      later, she developed idiopathic thrombocytopenic purpura (ITP) and was diagnosed
      with Evans' syndrome. Thereafter, laparoscopic splenectomy was performed because
      her autoimmune hemolytic anemia was refractory and dependent on steroid therapy.
      The HLA genotypes of the patient were HLA-A*020101/A* 2602, HLA-B*270502/B*5401,
      HLA-Cw*0102/Cw*020202, HLA-DRB1*0404/DRB1*0405, and HLA-DQB1*0302/DQ B1*0401.
      Hashimoto's thyroiditis is often associated with other nonendocrine autoimmune
      diseases, and antithyroid antibodies are frequently observed in Evans' syndrome
      (coexistence of AIHA and ITP). However, there is no report of Evans' syndrome
      developing in patients with overt hypothyroidism and Hashimoto's thyroiditis.
      This case suggests that three autoimmune diseases (AIHA, ITP, and Hashimoto's
      thyroiditis) might share a common immunogenetic pathway in pathogenesis.

PMID- 16807997
TI  - A case of hemolytic uremic syndrome caused by Escherichia coli O104:H4.
AB  - A 29-year-old woman presented with bloody diarrhea, abdominal pain, hemolytic
      anemia, thrombocytopenia, and acute renal failure. She was diagnosed with
      Escherichia coli O104:H4-associated hemolytic-uremic syndrome (HUS) and treated
      with plasmapheresis and hemodialysis for 3 weeks. She recovered without sequelae.
      To the best of our knowledge, this is the first report of Escherichia coli
      O104:H4-associated HUS in Korea. We recommend that Escherichia coli O104:H4, as
      well as the more common O157:H7, be considered in the diagnosis of bloody
      diarrhea-associated HUS.

PMID- 16807998
TI  - Tearing of the mitral valve during vent removal after a successful mitral valve
      repair: a beneficial role of transesophageal echocardiography.
AB  - In this case, a successful mitral valve repair was confirmed by transesophageal
      echocardiography (TEE) at the end of a cardiopulmonary bypass. The left
      ventricular vent was placed through the mitral valve to remove the air after the
      TEE examination, and on its way out, the left ventricular vent damaged the
      anterior mitral leaflet (AML). Re-examination of the valve with TEE detected the
      new mitral valve insufficiency. The CPB was reinstituted, and tearing of the
      lateral third part of the anterior mitral leaflet was found. This case emphasizes
      the importance of TEE in the operating room as a continuous monitor, not only to
      evaluate the result of the cardiac surgery, but also to detect any unpredictable
      events during the surgery.

PMID- 16807999
TI  - Toronto City Council adopts drug strategy.

PMID- 16808001
TI  - Australia: Court quashes sentence of man convicted for HIV transmission.

PMID- 16808000
TI  - Germany: study shows effectiveness of prison needle exchange.

PMID- 16808002
TI  - US: Arizona ordered to cover HIV-positive woman's organ transplant.

PMID- 16808003
TI  - Libya: Death sentences of foreign health care workers overturned.

PMID- 16808004
TI  - Abstracts of the Annual British Association for Sexual Health and HIV (BASHH)
      Spring Meeting, Nottingham, 2006.

PMID- 16808005
TI  - Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6)
      by alkamides of Piper nigrum.
AB  - Nineteen alkamides isolated from Piper nigrum L. were tested for their mechanism
      based inhibition on human liver microsomal dextromethorphan O-demethylation
      activity, a prototype marker for cytochrome P450 2D6 (CYP2D6). All compounds
      increased their inhibitory activity with increasing preincubation time. Among
      them, 15 and 17 showed more than 50 % decrease of the CYP2D6 residual activity
      after 20 min preincubation. Further investigations on 15 and 17 showed that the
      characteristic time- and concentration-dependent inhibition, which required a
      catalytic step with NADPH, was not protected by nucleophiles, and was decreased
      by the presence of a competitive inhibitor. The kinetic parameters for
      inactivation (kinact and KI) were 0.028 min-1 and 0.23 microM for 15 and 0.064
      min-1 and 0.71 microM for 17, respectively, which were stronger than the known
      mechanism-based inhibitor, paroxetine (a positive control). Thus, 15 and 17 are
      potent mechanism-based inhibitors of CYP2D6.

PMID- 16808006
TI  - [A construction worker with acute knee pain].
AB  - BACKGROUND: Out of all peripheral arterial aneurysms, 70% are located in the
      popliteal artery; less than 4% of these rupture. Ruptured popliteal aneurysms may
      be mistaken for deep venous thrombosis. MATERIAL AND METHODS: From March until
      June 2001 three patients were primarily admitted with a diagnosis of venous
      thrombosis. This delayed the appropriate treatment of a ruptured popliteal
      aneurysm considerably. Two patients were first anticoagulated with warfarin
      before being transferred to the surgical ward. All the patients were operated on
      with the exclusion of the popliteal aneurysm and a femoropopliteal bypass
      conduit. RESULTS: The haematoma from a ruptured popliteal aneurysm presenting
      with pain and venous swelling is easily mistaken for a deep venous thrombosis. In
      these three patients the correct diagnosis was made respectively 18, 2 and 20
      days after the onset of swelling and pain. INTERPRETATION: Ruptured popliteal
      aneurysms can be mistaken for a venous thrombosis or a Baker cyst. A Duplex scan
      will most often lead to a correct diagnosis. Surgery is mandatory. Delayed
      diagnosis and treatment increases morbidity and may lead to loss of limb.

PMID- 16808007
TI  - [Popliteal aneurysm--a rare, but important diagnosis].

PMID- 16808009
TI  - Abstracts of the 12th Annual Meeting of Human Brain Mapping, June 11-15, 2006,
      Florence, Italy.

PMID- 16808008
TI  - [International workshop on lysosomal storage disorders, December 2005, Athens,
      Greece].

PMID- 16808010
TI  - Instructions for repair.

PMID- 16808011
TI  - New regulations may breed new opportunities as buzz builds around insurance
      mandates.

PMID- 16808012
TI  - [Retroperitoneal hemangioma--a case report].
AB  - Localization of hemangioma in retroperineum causes late diagnosis of the disease.
      The tumour is usually detected only when the clinical symptoms caused by the
      pressure of the surrounding tissues occur. This article presents the case of
      retroperitoneal hemangioma preoperatively diagnosed as suspect feochromocytoma.

PMID- 16808013
TI  - Rickettsioses: from genome to proteome, pathobiology, and rickettsiae as an
      international threat. Proceedings of the 4th International Conference on
      Rickettsiae and Rickettsial Diseases. June 18-21, 2005. Logrono, Spain.

PMID- 16808014
TI  - Proceedings of the 5th Amino Acid Assessment Workshop. October 24-25, 2005. Los
      Angeles, California, USA.

PMID- 16808017
TI  - Selected papers from the Twenty-Fifth Annual Conference on Peritoneal Dialysis.
      February 28-March 2, 2005. Tampa, Florida, USA.

PMID- 16808016
TI  - Prevention of Assisted Suicide Act.

PMID- 16808018
TI  - You've got questions; we've got answers--maybe.

PMID- 16808019
TI  - Randomized open comparison of the safety of SLIT in a no-updosing and traditional
      updosing schedule in patients with Parietaria allergy.
AB  - BACKGROUND: Due to optimal safety of sublingual immunotherapy (SLIT), it was
      suggested that a slow up-dosing phase maybe not necessary, and therefore the
      treatment will be more patient-friendly, avoiding dosing mistakes. PATIENTS:
      Twenty adult patients suffering allergic rhinitis due to Parietaria, were
      enrolled. Half of them received the traditional schedule and the other half
      immediately started with 200 STU. RESULTS: No difference was observed between the
      traditional up-dosing treatment schedule and no-up-dosing treatment schedule in
      terms of side effects, even mild local side effects, even mild local side effects
      was greater with traditional regimen.

PMID- 16808020
TI  - 15-second triage tool. The use of capnography for the rapid assessment & triage
      of critically injured patients & victims of chemical terrorism.

PMID- 16808021
TI  - Pediatric DKA. The presentation, assessment & prehospital management of diabetic
      ketoacidosis in children.

PMID- 16808022
TI  - The effect of vitamin D as adjuvant therapy in pulmonary tuberculosis with
      moderate-advance lesion.

PMID- 16808023
TI  - Proceedings of the International Rhizosphere Congress 2004, Munich, Germany.

PMID- 16808024
TI  - Human Immunology: Patient-Based Research. Proceedings of a conference, May 16-18,
      2005, New York, New York, USA.

PMID- 16808025
TI  - Petsavers take a closer look at canine cruciates.

PMID- 16808026
TI  - Public Health Genetics: Experiences and Challenges. Proceedings of an
      International Symposium, February 19-21, 2004, Bielefeld, Germany.

PMID- 16808027
TI  - Hearts of wisdom: American women caring for kin, 1850-1940.  [Review of: Abel,
      E.K.  Hearts of wisdom: American women caring for kin, 1850-1940.  Cambridge,
      Mass.: Harvard U. Pr., 2000].

PMID- 16808028
TI  - Public vows: a history of marriage and the nation. [Review of: Cott, N.F. Public
      vows: a history of marriage and the nation. Cambridge, Mass.: Harvard U. Pr.,
      2000].

PMID- 16808029
TI  - Public vows: a history of marriage and the nation. [Review of: Cott, N.F. Public
      vows: a history of marriage and the nation.  Cambridge, Mass.: Harvard U. Pr.,
      2000].

PMID- 16808030
TI  - Nymphomania: a history. [Review of: Groneman, C. Nymphomania: a history. New
      York: Norton, 2000].

PMID- 16808031
TI  - Evidence-Based Approach to Optimal Management of HPEN Access. Proceedings of a
      consensus conference, January 27-28, 2005, Orlando, Florida, USA.

PMID- 16808032
TI  - The sanitary city: urban infrastructure in America from Colonial times to the
      present. [Review of: Melosi, M.V. The sanitary city: urban infrastructure in
      America from Colonial times to the present. Baltimore: Johns Hopkins U. Pr.,
      2000].

PMID- 16808033
TI  - Shades of citizenship: race and the census in modern politics. [Review of:
      Nobles, M. Shades of citizenship: race and the census in modern politics.
      Stanford: Stanford U. Pr., 2000].

PMID- 16808034
TI  - Medical geography in historical perspective. [Review of: Rupke, N.A., ed. Medical
      geography in historical perspective. London: Wellcome Inst. for the Hist. of
      Medicine, 2000].

PMID- 16808035
TI  - Attention and intention, decoded!

PMID- 16808036
TI  - Devices and desires: gender, technology, and American nursing. [Review of:
      Sandelowski, M. Devices and desires: gender, technology, and American nursing.
      Chapel Hill: U. of North Carolina Pr.; New York: Hill and Wang, 2000].

PMID- 16808037
TI  - BARS at the synapse: PICK-1 lipid binding domain regulates targeting,
      trafficking, and synaptic plasticity.

PMID- 16808038
TI  - Endovascular management of traumatic aortic injuries.

PMID- 16808039
TI  - Preoperative fasting.

PMID- 16808040
TI  - The village enlightenment in America: popular religion and science in the
      nineteenth century. [Review of: Hazen, C.J. The village enlightenment in America:
      popular religion and science in the nineteenth century. Urbana: U. of Illinois
      Pr., 2000].

PMID- 16808041
TI  - Raising the dead: readings of death and (black) subjectivity. [Review of:
      Holland, S.P. Raising the dead: readings of death and (black) subjectivity.
      Durham, N.C.: Duke U. Pr., 2000].

PMID- 16808042
TI  - Sexual liberation or sexual license?: the American revolt against Victorian
      sexuality. [Review of: White, K. Sexual liberation or sexual license?: the
      American revolt against Victorian sexuality. Chicago: Ivan R. Dee, 2000].

PMID- 16808043
TI  - 2-Arachidonoylglycerol (2-AG) membrane transport: history and outlook.
AB  - Only a few studies have addressed the transport of 2-arachidonoylglycerol (2-AG),
      a naturally occurring agonist for cannabinoid receptors. Based upon saturation
      kinetics, these early reports have proposed that 2-AG enters the cell by a
      specific 2-AG transporter, via the putative anandamide transporter, or by simple
      diffusion. In this review, the uptake of 2-AG is discussed in light of the recent
      advances that have been made for anandamide transport, where the mechanism
      appears to be rate-limited diffusion through the membrane. Endocannabinoids may
      be a distinct class of agonists since they are hydrophobic and neutral,
      exhibiting similar biophysical properties to some anesthetics that freely diffuse
      through the membrane.

PMID- 16808044
TI  - Mechanisms of methamphetamine-induced dopaminergic neurotoxicity.
AB  - Methamphetamine (METH) is a powerful stimulant of abuse with potent addictive and
      neurotoxic properties. More than 2.5 decades ago, METH-induced damage to
      dopaminergic neurons was described. Since then, numerous advancements have been
      made in the search for the underlying mechanisms whereby METH causes these
      persistent dopaminergic deficits. Although our understanding of these mechanisms
      remains incomplete, combinations of various complex processes have been described
      around a central theme involving reactive species, such as reactive oxygen and/or
      nitrogen species (ROS and RNS, respectively). For example, METH-induced
      hyperthermia, aberrant dopamine(DA), or glutamate transmission; or mitochondrial
      disruption leads to the generation of reactive species with neurotoxic
      consequences. This review will describe the current understanding of how high
      dose METH administration leads to the production of these toxic reactive species
      and consequent permanent dopaminergic deficits.

PMID- 16808045
TI  - Developmental toxicity of prenatal exposure to toluene.
AB  - Organic solvents have become ubiquitous in our environment and are essential for
      industry. Many women of reproductive age are increasingly exposed to solvents
      such as toluene in occupational settings (ie, long-term, low-concentration
      exposures) or through inhalant abuse (eg, episodic, binge exposures to high
      concentrations). The risk for teratogenic outcome is much less with low to
      moderate occupational solvent exposure compared with the greater potential for
      adverse pregnancy outcomes, developmental delays, and neurobehavioral problems in
      children born to women exposed to high concentrations of abused organic solvents
      such as toluene, 1,1,1-trichloroethane, xylenes, and nitrous oxide. Yet the
      teratogenic effects of abuse patterns of exposure to toluene and other inhalants
      remain understudied. We briefly review how animal models can aid substantially in
      clarifying the developmental risk of exposure to solvents for adverse
      biobehavioral outcomes following abuse patterns of use and in the absence of
      associated health problems and co-drug abuse (eg, alcohol). Our studies also
      begin to establish the importance of dose (concentration) and critical perinatal
      periods of exposure to specific outcomes. The present results with our clinically
      relevant animal model of repeated, brief, high-concentration binge prenatal
      toluene exposure demonstrate the dose-dependent effect of toluene on prenatal
      development, early postnatal maturation, spontaneous exploration, and amphetamine
      induced locomotor activity. The results imply that abuse patterns of toluene
      exposure may be more deleterious than typical occupational exposure on fetal
      development and suggest that animal models are effective in studying the
      mechanisms and risk factors of organic solvent teratogenicity.

PMID- 16808046
TI  - Endocannabinoid signaling directs periimplantation events.
AB  - An emerging concept in female reproduction is the role of endocannabinoids, a
      group of endogenously produced lipid mediators that bind to and activate
      cannabinoid receptors. Although adverse effects of cannabinoids in female
      reproduction have been implicated for years, the mechanisms by which they exert
      these effects remained elusive. With the identification of cannabinoid receptors,
      endocannabinoid ligands, their key synthetic and hydrolytic pathways, and the
      generation of knockout mouse models for cannabinoid receptors, a wealth of
      information is now available regarding the significance of
      cannabinoid/endocannabinoid signaling in early pregnancy. This review focuses on
      various aspects of endocannabinoid signaling in preimplantation embryo
      development and activation, and uterine differentiation during the
      periimplantation embryo-uterine dialog. It is hoped that a deeper understanding
      will lead to potential clinical applications of the endocannabinoid system as a
      target for regulating female fertility.

PMID- 16808047
TI  - A 28-year-old man with neck ache.

PMID- 16808048
TI  - British beef, Ontario water and dead crows.

PMID- 16808049
TI  - [On the 80th birthday of Academician Aleksandr Mikhailovich Ugolev (1926-1991)].

PMID- 16808050
TI  - Religious freedom and Indian rights: the case of Oregon v. Smith. [Review of:
      Long, C.N. Religious freedom and Indian rights: the case of Oregon v. Smith.
      Lawrence: U. Pr. of Kansas, 2000].

PMID- 16808051
TI  - Pious traders in medicine: a German pharmaceutical network in eighteenth-century
      North America. [Review of: Wilson, R. Pious traders in medicine: a German
      pharmaceutical network in eighteenth-century North America. University Park, Pa.:
      Penn State Pr., 2000].

PMID- 16808052
TI  - "Heal thyself": managing health care reform. [Review of: Armstrong, P., et al.
      "Heal thyself": managing health care reform. Toronto: Garamond, 2000].

PMID- 16808053
TI  - Committed to the state asylum: insanity and society in nineteenth-century Quebec
      and Ontario. [Review of: Moran, J.E. Committed to the state asylum: insanity and
      society in nineteenth-century Quebec and Ontario. Montreal: McGill-Queen's U.
      Pr., 2000].

PMID- 16808054
TI  - [The nursing profession: a history of caring in the hospitals of Quebec. (Review
      of: Cohen, Y. Profession infirmiere: une histoire des soins dans les hopitaux du
      Quebec. Montreal: Pr. de l'U. de Montreal, 2000)].

PMID- 16808055
TI  - [The evolution of the protection of children in Quebec: from its origins to our
      day. (Review of: Joyal, R., ed. L'evolution de la protection de l'enfance au
      Quebec: des origines a nos jours. Sainte-Foy, Que.: Pr. de l'U. Laval, 2000)].

PMID- 16808056
TI  - Josiah Gordon "Doc" Scurlock: physician, gunfighter, and family man.

PMID- 16808057
TI  - Hearts of wisdom: American women caring for kin, 1850-1940. [Review of: Abel,
      E.K. Hearts of wisdom: American women caring for kin, 1850-1940. Cambridge,
      Mass.: Harvard U. Pr., 2000].

PMID- 16808058
TI  - Increasing molecular mass allows better tumor targeting and retention of cancer
      therapy.

PMID- 16808059
TI  - New FACTT technique is conservatively over 1000-times more sensitive than ELISA.

PMID- 16808060
TI  - Cetuximab approved by FDA for treatment of head and neck squamous cell cancer.

PMID- 16808061
TI  - The sanitary city: urban infrastructure in America from colonial times to the
      present. [Review of: Melosi, M.V. The sanitary city: urban infrastructure in
      America from colonial times to the present. Baltimore: Johns Hopkins U. Pr.,
      2000].

PMID- 16808062
TI  - Biologists and the promise of American life: from Meriwether Lewis to Alfred
      Kinsey. [Review of: Pauly, P.J. Biologists and the promise of American life: from
      Meriwether Lewis to Alfred Kinsey. Princeton: Princeton U. Pr., 2000].

PMID- 16808063
TI  - The people's doctors: Samuel Thomson and the American botanical movement, 1790
      1860. [Review of: Haller, J.S., Jr. The people's doctors: Samuel Thomson and the
      American botanical movement, 1790-1860. Carbondale: Southern Illinois U. Pr.,
      2000].

PMID- 16808064
TI  - The loves of the plants; or, the cross-fertilization of science and desire at the
      end of the eighteenth century.

PMID- 16808065
TI  - The biomechanical response of spinal cord tissue to uniaxial loading.
AB  - The spinal cord is an integral component of the spinal column and is prone to
      physical injury during trauma or more long-term pathological insults. The
      development of computational models to simulate the cord-column interaction
      during trauma is important in developing a proper understanding of the injury
      mechanism. Such models would be invaluable in seeking both preventive strategies
      that reduce the propensity for injury and identifying specific treatment regimes.
      However, these developments are hampered by the limited information available on
      the structural and mechanical properties of this soft tissue owing to the
      difficulty in handling this material in a cadaveric situation. The purpose of the
      present paper is to report the rapid deterioration in the quality of the tissues
      once excised, which provides a further challenge to the successful elucidation of
      the structural properties of the tissue. In particular, the tangent modulus of
      the tissue is seen to increase sharply over a period of 72 h.

PMID- 16808066
TI  - Comparison of kinematics between thoracolumbar T11-t12 and T12-L1 functional
      spinal units.
AB  - The purpose of this study was to compare the kinematics in terms of the locations
      and loci of instantaneous axes of rotation (IARs) at levels T11-T12 and T12-L1 of
      thoracolumbar junction (TLJ). The LAR is one of the kinematics characteristics of
      a functional spinal unit (FSU) in a plane under load. There is little information
      about loci of IARs in the TLJ. Validated finite element (FE) models of T11-T12
      and T12-L1 FSUs were used to determine the locations and loci of IARs in three
      anatomical planes. In the sagittal plane, the locations and loci of the IARs were
      located below the intervertebral disc for T11-T12, and situated in the
      intervertebral disc for T12-L1. In the frontal plane, they were all located
      around the mid-sagittal plane for T11-T12 and T12-L1. In the transverse plane,
      they fell in the medio-anterior region of the movable vertebra T11 for T11-T12,
      and located near the cortical shell of the upper vertebra T12 for T12-L1. These
      findings may offer an insight to better understanding the kinematics of the human
      thoracolumbar spine and provide clinically relevant information for the
      evaluation of spinal stability and functionality of implant devices.

PMID- 16808067
TI  - Layer manufacturing for in vivo devices.
AB  - Traditional in vivo devices fabricated to be used as implantation devices
      included sutures, plates, pins, screws, and joint replacement implants. Also,
      akin to developments in regenerative medicine and drug delivery, there has been
      the pursuit of less conventional in vivo devices that demand complex architecture
      and composition, such as tissue scaffolds. Commercial means of fabricating
      traditional devices include machining and moulding processes. Such manufacturing
      techniques impose considerable lead times and geometrical limitations, and
      restrict the economic production of customized products. Attempts at the
      production of non-conventional devices have included particulate leaching,
      solvent casting, and phase transition. These techniques cannot provide the
      desired total control over internal architecture and compositional variation,
      which subsequently restricts the application of these products. Consequently,
      several parties are investigating the use of freeform layer manufacturing
      techniques to overcome these difficulties and provide viable in vivo devices of
      greater functionality. This paper identifies the concepts of rapid manufacturing
      (RM) and the development of biomanufacturing based on layer manufacturing
      techniques. Particular emphasis is placed on the development and experimentation
      of new materials for bio-RM, production techniques based on the layer
      manufacturing concept, and computer modelling of in vivo devices for RM
      techniques.

PMID- 16808068
TI  - Selective laser sintering of hydroxyapatite reinforced polyethylene composites
      for bioactive implants and tissue scaffold development.
AB  - Selective laser sintering (SLS) has been investigated for the production of
      bioactive implants and tissue scaffolds using composites of high-density
      polyethylene (HDPE) reinforced with hydroxyapatite (HA) with the aim of achieving
      the rapid manufacturing of customized implants. Single-layer and multilayer block
      specimens made of HA-HDPE composites with 30 and 40 vol % HA were sintered
      successfully using a CO2 laser sintering system. Laser power and scanning speed
      had a significant effect on the sintering behaviour. The degree of particle
      fusion and porosity were influenced by the laser processing parameters, hence
      control can be attained by varying these parameters. Moreover, the SLS processing
      allowed exposure of HA particles on the surface of the composites and thereby
      should provide bioactive products. Pores existed in the SLS-fabricated composite
      parts and at certain processing parameters a significant fraction of the pores
      were within the optimal sizes for tissue regeneration. The results indicate that
      the SLS technique has the potential not only to fabricate HA-HDPE composite
      products but also to produce appropriate features for their application as
      bioactive implants and tissue scaffolds.

PMID- 16808069
TI  - Finite element analysis of the long-term fixation strength of cemented ceramic
      cups.
AB  - Clinical studies have shown that adequate fixation of ceramic cups using bone
      cement is difficult to achieve. As the cement-ceramic bond strength is low, a
      satisfactory fixation strength requires a cup design that allows mechanical
      interlocking, although such a design will probably promote cement cracking and
      therefore cup loosening in the long term. An investigation has been carried out
      to establish whether a cemented ceramic cup can be designed in such a way that
      both a satisfactory initial fixation strength is obtained and cement cracking is
      reduced to levels found around PE cups functioning well in vivo. By means of
      finite element analysis, the fatigue loading of three geometrically different
      cemented acetabular cups, with ceramic and PE material properties, has been
      simulated, and the severity of the crack patterns produced in the cement has been
      analysed. Furthermore, the fixation strength has been analysed by simulating a
      pull-out test prior to and after fatigue testing. All ceramic cups produced much
      larger amounts of cement damage during fatigue testing than any PE cup, caused by
      stress concentrations in the cement that were attributable to the high stiffness
      of the ceramic. Even a completely smooth ceramic cup produced more damage than a
      sharp-grooved PE cup. Owing to the excessive cement cracking, the fixation
      strength of the ceramic cups dropped after fatigue loading. It is concluded that
      cemented ceramic cups have an increased risk of long-term mechanical failure by
      comparison with PE cups, and that a ceramic cup design that combines sufficient
      fixation strength with low cement failure may be difficult to achieve.

PMID- 16808070
TI  - Effect of lubricant composition on the fatigue properties of ultra-high molecular
      weight polyethylene for total knee replacement.
AB  - Ultrahigh molecular weight polyethylene (UHMWPE) fatigue is a critical factor
      affecting the longevity of total knee replacement (TKR) bearings. With the
      increased need for laboratory studies to mimic near in vivo conditions for
      accurate characterization of material performance, the present study investigated
      the role of hyaluronic acid (HA) in testing lubricant on the crack growth
      response of UHMWPE. It was hypothesized that the change in lubricant viscosity as
      a result of HA would affect the fatigue life of the polymer. A fracture mechanics
      approach as per ASTM E 647 was adopted for this study. Surface micrograph and
      surface chemistry analyses were employed to study the micromechanisms of fatigue
      failure and protein adsorption of the specimen surfaces. Rheological analysis
      indicated that the addition of HA to diluted bovine serum increased testing
      lubricant viscosity. HA concentrations of 2.22, 0.55, and 1.5 g/l closely matched
      the viscosity ranges reported for osteoarthritis, rheumatoid arthritic diseased
      joint fluid, and periprosthetic fluids respectively. Results showed that the
      addition of HA to standard diluted bovine serum lubricants, in concentrations
      similar to that of periprosthetic fluid, delayed crack initiation and crack
      growth during fatigue testing.

PMID- 16808071
TI  - A new approach to C2 continuous piecewise bicubic representation of the articular
      surfaces of diarthrodial joints.
AB  - Based on the force-deflection equation for a beam subjected to lateral point
      loads, a C2 continuous piecewise bicubic mathematical representation was proposed
      to model complicated geometrical surfaces, e.g. the articular surfaces of human
      joints. The method was then extended so that it could be used for mathematical
      modelling of incomplete nets of data points, as well as smoothing of noisy and/or
      filtering of erroneous data points. Mathematical techniques were also developed
      to calculate the required unknown parameters explicitly, with no need to solve
      the system of equations simultaneously. The performance of the proposed method
      was evaluated on a number of surface modelling problems, including two known
      analytical surfaces and the human femoral and patellar articular surfaces. The
      results indicate that the proposed method is precise, flexible, and easy to apply
      and has several advantages over the conventional smoothing methods, i.e. the B
      spline approach.

PMID- 16808072
TI  - The biomechanical effect of vertebroplasty on the adjacent vertebral body: a
      finite element study.
AB  - The increased use of vertebroplasty for the treatment of osteoporotic vertebral
      compression fractures has led to concerns that the technique may increase the
      risk of fracture in the adjacent vertebrae. The aim of this study was to simulate
      the biomechanical effects of vertebroplasty using an osteoporotic two-vertebrae
      finite element model. Following a simulated compression fracture, the model was
      augmented with one of three volumes of PMMA-based cement or left untreated. Upon
      reloading, an increase in segment stiffness was found with increasing volumes of
      cement. However, in all the treated models there was an increase in endplate
      deflection into the adjacent vertebra causing plastic failure of the surrounding
      trabecular bone. More damage was caused in the adjacent vertebra of the treated
      models than in the untreated model. The model results suggest that clinicians
      should be wary of using standard vertebroplasty cements to treat compression
      fractures in patients with highly osteoporotic bone.

PMID- 16808073
TI  - Effects of ageing on the biomechanical properties of rat articular cartilage.
AB  - Previous studies have demonstrated that male Sprague Dawley (SD) rats experience
      age-related bone loss with the same characteristics as that in ageing men. As
      articular cartilage, like bone, is a critical component of the health and
      function of the musculoskeletal system, the authors hypothesized that articular
      cartilage in the untreated male SD rats could be a suitable model for studying
      the age-related deterioration of articular cartilage in men. To test this
      hypothesis, male SD rats were killed at between 6 and 27 months. The right femur
      of each rat was removed. The effects of ageing on the structural integrity of the
      distal femoral articular cartilage were studied by biomechanical testing with a
      creep indentation apparatus. The aggregate modulus, Poisson's ratio,
      permeability, thickness, and percentage recovery of articular cartilage were
      determined using finite element/non-linear optimization modelling. No significant
      differences were observed in these biomechanical properties of the distal femoral
      articular cartilage as a function of age. Therefore, untreated male SD rats
      appear to be unsuitable for studying the age-related changes of articular
      cartilage as they occur in men. However, and more intriguingly, it is also
      possible that ageing does not affect the biomechanical properties of articular
      cartilage in the absence of cartilage pathology.

PMID- 16808074
TI  - A review of magnetic resonance imaging compatible manipulators in surgery.
AB  - Developments in magnetic resonance imaging (MRI), coupled with parallel progress
      in the field of computer-assisted surgery, mean that an ideal environment has
      been created for the development of MRI-compatible robotic systems and
      manipulators, capable of enhancing many types of surgical procedure. However, MRI
      does impose severe restrictions on mechatronic devices to be used in or around
      the scanners. In this article a review of the developments in the field of MRI
      compatible surgical manipulators over the last decade is presented. The
      manipulators developed make use of different methods of actuation, but they can
      be reduced to four main groups: actuation transmitted through hydraulics,
      pneumatic actuators, ultrasonic motors based on the piezoceramic principle and
      remote manual actuation. Progress has been made concerning material selection,
      position sensing, and different actuation techniques, and design strategies have
      been implemented to overcome the multiple restrictions imposed by the MRI
      environment. Most systems lack the clinical validation needed to continue on to
      commercial products.

PMID- 16808075
TI  - Thermoelastic analysis of high-pressure angioplasty balloons.
AB  - Failures in angioplasty balloons are investigated using typical destructive
      techniques. The material properties of moulded balloons are derived from tensile
      tests and used to establish the reasons for failure of the balloons.
      Thermoelastic stress analysis is used to determine the stress distribution in the
      balloons, and a means of interpreting the data to derive actual stresses is
      described. The departure from linear elastic behaviour in the angioplasty
      balloons is identified using thermoelastic analysis. The results from the
      thermoelastic analysis are discussed and compared with those from the destructive
      tests, and the thermoelastic technique is shown to be a potential new means for
      non-destructive analysis of angioplasty balloons.

PMID- 16808076
TI  - Effects of ascorbic acid concentration on the tissue engineering of the
      temporomandibular joint disc.
AB  - The temporomandibular joint (TMJ) disc is a specialized fibrocartilaginous
      tissue. When the disc becomes an obstacle and becomes damaged, surgeons have no
      choice but to perform a discectomy. Tissue engineering may provide a novel
      treatment modality for TMJ disorder patients who undergo discectomy. No studies
      have been conducted on the most favourable media for TMJ disc cells. The
      objective of the current study was to examine the effects on biochemical and
      biomechanical properties of varying ascorbic acid concentrations (0, 25, or 50
      microg/ml) on TMJ disc cells seeded on non-woven PGA scaffolds. The ascorbic acid
      concentration of the 25 microg/ml group resulted in more effective cell seeding
      of the scaffolds, with 1.53 million cells per construct, by comparison with the 0
      and 50 microg/ml groups which had 1.20 million and 1.32 million cells per
      scaffold respectively. At week 4, the 25 microg/ml group had a higher collagen
      content than the 0 microg/ml group, with 30.4 +/- 2.7 and 24.9 +/- 3.3 microg of
      collagen per construct respectively. The 25 microg/ml group had a higher
      aggregate modulus than the 50 microg/ml group, with values of 6.1 +/- 1.3 and 4.0
      +/- 0.9 kPa respectively at week 4. The results of this study indicate that the
      use of 25 microg/ml of ascorbic acid in culture media is effective for the tissue
      engineering of the TMJ disc, significantly outperforming media without or with 50
      microg/ml of ascorbic acid.

PMID- 16808077
TI  - Validation of the soft tissue restraints in a force-controlled knee simulator.
AB  - In vitro testing of total knee replacements (TKRs) is important both at the
      design stage and after the production of the final components. It can predict
      long-term in vivo wear of TKRs. The two philosophies for knee testing are to
      drive the motion by displacement or to drive the motion by force. Both methods
      have advantages and disadvantages. For force control an accurate simulation of
      soft tissue restraints is required. This study was devised to assess the accuracy
      of the soft tissue restraints of the force-controlled Stanmore knee simulator in
      simulating the restraining forces of the anterior cruciate ligament (ACL) and
      posterior cruciate ligament (PCL). In order to do this, human cadaver knee joints
      were subjected to the ISO Standard Walking Cycle. The resulting kinematics were
      monitored when the soft tissue structures were intact, when the ACL and PCL were
      resected, and when they were simulated by springs positioned anteriorly and
      posteriorly. The stiffness of the springs was determined from the literature. Two
      different stiffnesses of springs were used which were 7.24 N/mm (designated as
      soft springs) and 33.8 N/mm (designated as hard springs). All the intact knees
      showed displacements that were within the range of the machine. Cutting the ACL
      and PCL resulted in anterior and posterior motion and internal external rotation
      that were significantly greater than the intact knee. Results showed that when
      the ACL and PCL were cut hard springs positioned anterior and posterior to the
      knee returned the knee to near normal anterior-posterior (AP) motion. Using hard
      springs in the posterior position in any condition reduced rotational
      displacements. Therefore using springs in a force-controlled simulator is a
      compromise. More accuracy may be obtained using springs that are of intermediate
      stiffness.

PMID- 16808078
TI  - The predictive power of surface profile parameters on the amount of wear measured
      in vitro on metal-on-polyethylene artificial hip joints.
AB  - Various studies report a weak correlation between the average surface roughness
      R(a) of metallic ballheads and the observed wear rate of the polyethylene cups
      coupled to them. The aim of this study is to verify, with controlled in vitro
      experiments, whether other parameters such as the total roughness R(t), and the
      skewness R(sk) are better predictors of the polyethylene wear when the metallic
      heads present a surface conditioning that varies substantially from specimen to
      specimen, as is usually the case with retrieved specimens. Twelve CoCrMo (cobalt
      chromium-molybdenum) ballheads were intentionally damaged in order to reproduce a
      wide spectrum of surface conditioning and were then subjected to the standard
      wear test against polyethylene cups, using a hip joint wear simulator. After 2 x
      10(6) cycles the weight lost by the cups was assessed with a gravimetric
      procedure, and the surface roughness of the metallic ballheads was qualified in
      terms of R(a), R(t), and R(sk). The various parameters were correlated to the
      weight loss using a linear regression analysis. The skewness R(sk) showed a
      coefficient linear regression R2 = 0.80, while the average roughness R(a), used
      in most previous studies, presented an R2 = 0.56. It was concluded that when
      specimens with substantially different surface conditioning are compared, as in
      retrievals analysis, it is also important to report the skewness R(sk) so that
      qualify the surface roughness of the specimens can be qualified.

PMID- 16808079
TI  - The stability of the femoral component of a minimal invasive total hip
      replacement system.
AB  - In this study, the initial stability of the femoral component of a minimal
      invasive total hip replacement was biomechanically evaluated during simulated
      normal walking and chair rising. A 20 mm diameter canal was created in the
      femoral necks of five fresh frozen human cadaver bones and the femoral heads were
      resected at the smallest cross-sectional area of the neck. The relatively short,
      polished, taper-shaped prostheses were cemented centrally in this canal according
      to a standardized procedure. A servohydraulic testing machine was used to apply
      dynamic loads to the prosthetic head. Radiostereophotogrammetric analysis was
      used to measure rotations and translations between the prosthesis and bone. In
      addition, the reconstructions were loaded until failure in a static, displacement
      controlled test. During the dynamic experiments, the femoral necks did not fail
      and no macroscopical damage was detected. Maximal values were found for normal
      walking with a mean rotation of about 0.2 degrees and a mean translation of about
      120 microm. These motions stabilized during testing. The mean static failure load
      was 4714 N. The results obtained in this study are promising and warrant further
      development of this type of minimal invasive hip prosthesis.

PMID- 16808080
TI  - On the biomechanical stability of cementless straight conical hip stems.
AB  - The aim of the present study was to investigation in vitro the effect of
      deficient bone-implant contact on the primary stability of a straight conical
      stem. Various possible deficient contact patterns were derived from surgical
      simulations. The effect of stair climbing loads on the bone-implant micromotion
      was firstly investigated using a finite element model and then an in vitro test
      aimed at assessing primary stability. It was found that if the surface features
      are prevented from biting dense bone in a few small but critical regions, stem
      primary stability is completely lost. These results suggest that the surface
      features used in the axisymmetric stem under investigation can be too sensitive
      to deficient contact conditions, and thus should be augmented with additional
      antirotational fins. Preliminary tests showed that a stem with the addition of
      such fins presents good primary stability in all tested conditions.

PMID- 16808081
TI  - Three dimensional stereolithography models of cancellous bone structures from
      muCT data: testing and validation of finite element results.
AB  - Stereolithography (STL) models of complex cancellous bone structures have been
      produced from three-dimensional micro-computed tomography data sets of human
      cancellous bone histological samples from four skeletal sites. The STL models
      have been mechanically tested and the derived stiffness compared with that
      predicted by finite element analysis. The results show a strong correlation (R2 =
      0.941) between the predicted and calculated stiffnesses of the structures and
      show promise for the use of STL as an additional technique to complement the use
      of finite element models, for the assessment of the mechanical properties of
      complex cancellous bone structures.

PMID- 16808082
TI  - PTSD, risk factors, and expectations among women having a baby: a two-wave
      longitudinal study.
AB  - INTRODUCTION: The aim of the study was to evaluate the incidence of chronic post
      traumatic stress disorder (PTSD) after childbirth in relation to pre-partum
      variables (personality characteristics, anamnestic risk factors) and intra-partum
      obstetrical and neonatal variables. Since expectations before an event could
      modify the perceptions, reactions, and satisfaction afterward, the
      representations of the idealized delivery were carefully analyzed. Moreover, the
      real and desired help perception from physicians and family members were
      separately considered during pregnancy and after delivery in relation to PTSD.
      METHOD: The study was carried out submitting a questionnaire to pregnant women
      twice: firstly when women were in their 38 << 42 gestational week (Time 1) and
      secondly after 3-6 months from childbirth (Time 2). 93 women were recruited at a
      University City Hospital in Milan, Italy. PTSD subscales, depression, and anxiety
      levels were also assessed. RESULTS: 2.4% of women had a complete PTSD, while
      32.1% of them resulted in having one or two positive subscales of symptoms: 15.5%
      (N = 13) had a positive intrusion subscale, 25.0% (N = 21) had a positive arousal
      subscale, while only 3.6% (N = 3) had a positive avoidance subscale. Pre-delivery
      depression influences PTSD, but only for the intrusion subscale. Pre-delivery
      physical risk factors are linked to PTSD on the avoidance subscale. At Time 2
      depression and PTSD are often present simultaneously. Given the high percentage
      of healthy newborns, intra-partum obstetrical variables do not seem to influence
      PTSD. High trait anxiety distinctively coexists with a specific expected delivery
      and a 'deception' in desired and real support from professionals. CONCLUSIONS:
      Childbirth is a risk condition for PTSD, depression during pregnancy influences
      the intrusion subscale, while having physical problems influences the arousal
      subscale. Expectations and support are modulated by the anxiety levels and they
      are not directly related to chronic PTSD.

PMID- 16808083
TI  - Relational factors in psychopathological responses to childbirth.
AB  - Childbirth can represent for women the time of greatest vulnerability experience,
      often associated with being out of control, loneliness or sadness. One hundred
      and sixty women who had 'normal' births were assessed within 48 hours on
      potential predictive measures and at 3-6 months post-partum for PTSD. Symptoms of
      depression, anxiety, perceived and desired support by family members, friends,
      medical personnel were also assessed. t-Test and chi-square were used to analyze,
      differences between 'risk group' and 'non-risk group'. Few women (1.25%) showed
      questionnaire responses suggesting clinically significant levels on PTSD; other
      women (28.75%) reported clinically significant symptoms for at least one
      subscale. Being at the first delivery experience, together with perceptions of
      low levels of support from family members and medical personnel, were found to be
      related to experience of post-traumatic stress symptoms. Anxiety for the child
      and previous depression are also related to such symptoms. Moreover, anxiety and
      depression are related to a difficult recognition of the support received, as
      well as to the desire for more support, in the care of the newborn, from medical
      professionals.

PMID- 16808084
TI  - Towards a conceptual framework for understanding post-traumatic stress symptoms
      following childbirth and implications for further research.
AB  - This paper provides a synthesis of current knowledge about post-traumatic stress
      symptoms following childbirth. In particular it presents a two dimensional
      conceptual framework for understanding the development of symptoms based upon
      predisposing (pre-pregnancy/pregnancy), precipitating (perinatal) and maintaining
      (postnatal) factors, which relate to internal (within individual), external
      (environmental) and interactional factors. In addition key methodological issues
      and areas for further research are identified.

PMID- 16808085
TI  - Post-traumatic symptoms after childbirth: what should we offer?
AB  - Most studies on post-traumatic stress symptoms after childbirth have focused on
      prevalence of and looked at etiological factors and predictors. While most
      authors agree that around 1.5% of the women develop post-traumatic stress
      disorder (PTSD) and significantly more present with post-traumatic stress
      symptoms, the studies still lack a proper diagnosis using diagnostic interviews
      to validate the enhanced stress scores found in questionnaires. Also, some
      relevant predicting factors such as pre-existing psychopathology and dissociation
      during labor have not been investigated so far. Mostly, however, research on
      counseling strategies for women with post-traumatic symptoms after childbirth has
      been neglected. While most women remain in a mother-child unit during the first
      days after birth, there is a unique opportunity to systematically assess birth
      experience in this setting and screen for women at risk for developing trauma
      symptoms. This article presents a multilevel counseling approach including
      postnatal counseling and counseling in a subsequent pregnancy.

PMID- 16808086
TI  - The longitudinal course of post-traumatic stress after childbirth.
AB  - Post-traumatic stress was assessed in early and late pregnancy, and 1, 4, 7, and
      11 months postpartum by means of questionnaires among 1224 women. Thirty-seven
      women (3%) had post-traumatic stress (meeting criteria B, C, and D for PTSD) at
      least once within 1-11 months postpartum. In pregnancy, depression, severe fear
      of childbirth, 'pre'-traumatic stress, previous counseling related to
      pregnancy/childbirth, and self-reported previous psychological problems were
      associated with an increased risk of having post-traumatic stress within 1-11
      months postpartum. Sum-scores of post-traumatic stress did not decrease over time
      among women who at least once had post-traumatic stress (criteria B, C, and D)
      within 1-11 months postpartum. Women with post-traumatic stress also showed a
      decrease in perceived social support over time postpartum.

PMID- 16808087
TI  - Are therapeutic ultrasound units a potential vector for nosocomial infection?
AB  - BACKGROUND AND PURPOSE: Nosocomial infections present a widespread problem in
      today's healthcare environment, with a significant number of patients acquiring
      an infection annually. With the contemporary transition of immunocompromised and
      high-risk patients to community-based care, therapeutic ultrasound has the
      potential to be a vector of infection in the physiotherapy setting. The purpose
      of the present study was to determine the degree of contamination on therapeutic
      ultrasound transducer heads and ultrasound gel after routine clinical use, and to
      evaluate the efficacy of recommended infection control procedures. METHOD: The
      study consisted of two phases. Using a prospective cross-sectional design,
      microbiological cultures were obtained from 44 transducer heads and 43 gels.
      Subjects were drawn from a variety of physiotherapy practice settings. All
      samples containing more than five colony forming units per cm2 were considered
      contaminated. Following these measurements, a repeated-measures design was used
      to re-evaluate the 44 transducer heads for the amount and type of bacteria
      present after cleaning with a 70% alcohol wipe. RESULTS: Twenty-seven per cent of
      transducer heads and 28% of gels were contaminated. Transducer heads showed
      fairly low levels of contamination across the sample, with the majority of
      organisms isolated found in normal skin and environmental flora. Gels were
      heavily contaminated with opportunistic and potentially pathogenic organisms,
      including Stenotrophomonas maltophilia, Staphylococcus aureus, Acinetobacter
      baumannii and Rhodotorula mucilaginosa. No multi-resistant organisms were
      identified. Cleaning with 70% alcohol significantly reduced the level of
      contamination on transducer heads (p < 0.01). CONCLUSIONS: Therapeutic ultrasound
      equipment is a potential vector for nosocomial infection in physiotherapy
      patients. The risk of infection from transducer heads can be effectively removed
      by cleaning with 70% alcohol between patients. Further research into possible
      strategies to reduce the risk of infection from ultrasound gels is needed.

PMID- 16808088
TI  - Therapists' experiences and perceptions of teamwork in neurological
      rehabilitation: reasoning behind the team approach, structure and composition of
      the team and teamworking processes.
AB  - BACKGROUND AND PURPOSE: Teamwork and the interdisciplinary team approach have
      been strongly advocated for use in the provision of neurological rehabilitation
      services. However, whether teamwork has been adopted, and in what form, has yet
      to be established. The present study investigated therapists' experiences and
      perceptions of the reasoning behind the team approach in neurological
      rehabilitation, the structure and composition of the team within which they
      worked and the team working process. METHOD: This article reports part of an
      exploratory qualitative study. Five occupational therapists and five
      physiotherapists from three teams: a rehabilitation centre; a community team; and
      a stroke unit based within the UK. Semi-structured interviews were undertaken
      with each participant and then transcribed. Content and thematic analysis of the
      qualitative interview data was carried out, with respondents validating both the
      transcription and analysis stages. RESULTS: Perceived composition and structure
      of the neurological rehabilitation team was variable across teams and between
      individual team members. There was disparity as to whether patients were included
      within the neurological team; the interdisciplinary team approach had not been
      consistently adopted and there were sub-teams and other team memberships in
      existence. Reasoning behind the team approach supported the perceived benefits of
      teamwork from a number of perspectives, and the activities reported as part of
      the team process were diverse. CONCLUSIONS: Different teams may choose to use
      different strategies depending on the aims and context of the team effort. In
      some instances interdisciplinary teamwork and patient-centred approaches were not
      adopted consistently and the process of teamwork itself is both complex and
      diverse.

PMID- 16808089
TI  - Item analysis of the NHANES ADL instrument in a sample of patients reporting
      frequent severe headaches.
AB  - BACKGROUND AND PURPOSE: The National Health and Nutrition Examination Surveys
      (NHANES) activity of daily living (ADL) instrument is a 16-item questionnaire
      designed to represent the internal latent construct of activities of daily
      living. The purpose of the present study was to measure selected psychometric
      properties (dimensionality, internal consistency and individual item response) of
      the NHANES ADL instrument on a population of patients who reported frequent
      severe headaches. METHOD: The study group consisted of 672 attendees of a
      traditional medical appointment with a report of severe headaches. Data analyses
      included exploratory factor analysis, internal consistency measures and graded
      item response theory. RESULTS: The NHANES ADL instrument is a uni-dimensional and
      internally consistent measure of activities of daily living. Graded item response
      theory analyses indicated that all 16 single items were sensitive measures of the
      latent construct of activities and daily living. Selected items demonstrated high
      discrimination while others demonstrated moderate discrimination among responses.
      CONCLUSION: Individual use of selected items of the NHANES ADL instrument may
      further improve the capacity of the healthcare provider in measuring and
      recording dysfunction associated with headaches.

PMID- 16808090
TI  - Evidence based practice: a survey of physiotherapists' current practice.
AB  - BACKGROUND AND PURPOSE: [corrected] Evidence-based practice is the explicit use
      of current best evidence in making decisions about the care of individual
      patients and is a concept of growing importance for physiotherapy. The aim of the
      present study was to investigate Australian physiotherapists' self-reported
      practice, skills and knowledge of evidence-based practice and to examine
      differences between recent and experienced graduates, physiotherapists with low
      and high levels of training and physiotherapists working in private practice and
      hospital settings. METHOD: A survey was sent to 230 physiotherapists working in
      hospitals and in private practice. One hundred and twenty-four were completed and
      returned. RESULTS: Although 69.4% of respondents said they frequently (at least
      monthly) read research literature, only 10.6%, 15.3% and 26.6% of respondents,
      respectively, searched PEDro, Cochrane and Medline or Cinahl databases
      frequently, and only 25.8% of respondents reported critically appraising research
      reports. Recent graduates rated their evidence-based practice skills more highly
      than more experienced graduates, but did not perform evidence-based practice
      tasks more often. Physiotherapists with higher levels of training rated their
      evidence-based practice skills more highly, were more likely to search databases
      and to understand a range of evidence-based practice terminology than those with
      lower levels of training. Private practice and hospital physiotherapists rated
      their evidence-based practice skills equally and performed most evidence-based
      practice activities with equal frequency. CONCLUSIONS: Respondents had a positive
      attitude toward evidence-based practice and the main barriers to evidence-based
      practice were time required to keep up to date, access to easily understandable
      summaries of evidence, journal access and lack of personal skills in searching
      and evaluating research evidence. Efforts to advance evidence-based practice in
      physiotherapy should focus on reducing these barriers.

PMID- 16808091
TI  - Balance and gait improved in patients with MS after physiotherapy based on the
      Bobath concept.
AB  - BACKGROUND AND PURPOSE: Patients with multiple sclerosis (MS) tend to have
      movement difficulties, and the effect of physiotherapy for this group of patients
      has been subjected to limited systematic research. In the present study
      physiotherapy based on the Bobath concept, applied to MS patients with balance
      and gait problems, was evaluated. The ability of different functional tests to
      demonstrate change was evaluated. METHOD: A single-subject experimental study
      design with ABAA phases was used, and two patients with relapsing-remitting MS in
      stable phase were treated. Tests were performed 12 times, three at each phase: A
      (at baseline); B (during treatment); A (immediately after treatment); and A
      (after two months). The key feature of treatment was facilitation of postural
      activity and selective control of movement. Several performance and self report
      measures and interviews were used. RESULTS: After intervention, improved balance
      was shown by the Berg Balance Scale (BBS) in both patients, and improved quality
      of gait was indicated by the Rivermead Visual Gait Assessment (RVGA). The
      patients also reported improved balance and gait function in the interviews and
      scored their condition as 'much improved'. Gait parameters, recorded by an
      electronic walkway, changed, but differently in the two patients. Among the
      physical performance tests the BBS and the RVGA demonstrated the highest change,
      while no or minimal change was demonstrated by the Rivermead Mobility Index (RMI)
      and Ratings of Perceived Exertion (RPE). CONCLUSION: The findings indicate that
      balance and gait can be improved after physiotherapy based on the Bobath concept,
      but this should be further evaluated in larger controlled trials of patients with
      MS.

PMID- 16808092
TI  - Case report: physiotherapy cuts the dose of botulinum toxin.
AB  - BACKGROUND AND PURPOSE: Cervical dystonia is a complex chronic neurological
      disorder which is more commonly managed with pharmacological interventions.
      METHOD: This Case Report outlines the rehabilitation of a patient who was able to
      reduce the effective dose of botulinum toxin when physiotherapy management was
      added to a long- term pharmacological regime. CONCLUSIONS: A good outcome is
      demonstrated from a combined physiotherapy and botulinum toxin intervention.

PMID- 16808093
TI  - [Epidemiologic characteristic of hepatitis B in the Splitsko-Dalmatinska County].
AB  - Epidemiologic characteristics of hepatitis B virus (HBV) infection in the Split
      Dalmatia County and in Croatia as a whole from January 1, 1994 till December 31,
      2003 were analyzed. The mean number of hepatitis B cases was 28 (morbidity rate
      6.03 per thousand) in the Split-Dalmatia County and 208 (morbidity rate 4.68 per
      thousand) in Croatia. Over the last five years, there was a marked decrease in
      the incidence of hepatits B in the Split-Dalmatia County (morbidity rate 1.55 per
      thousand), whereas its incidence at the national level showed a stable pattern
      (morbidity rate 4.49 per thousand). In the Split-Dalmatia County, the majority of
      patients (57.51%) were aged 15-29, which could be attributed to risky sexual
      contacts and intravenous drug use. The male to female ratio was 2.1(188:93).
      There was no major incidence fluctuation according to months of year. The
      hepatitis B mortality rate was 0.24% (5/2079) in Croatia as a whole, whereas no
      case of HBV lethality was recorded in the Split-Dalmatia County. The significant
      decrease in the hepatitis B morbidity rate in the Split-Dalmatia County most
      probably resulted from the comprehensive measures of prevention, especially
      vaccination, the early introduction of the needle exchange program (1955-1996).

PMID- 16808094
TI  - [Prostate carcinoma patients treated in county hospital Cakovec in past two
      years].
AB  - Prostate carcinoma is an important cause of morbidity and mortality in men of
      middle and older age. It is second diagnosed malignant tumor among men in USA and
      in Europe. Hereby, we'd like to show the number of treated patients at our
      hospital between January 2002 and January 2004. We made a retrospective analysis
      of patients' histories, discharge letters and operation protocols. During that
      period 70 transrectal biopsies (12 cilindars) were made, finding prostate
      carcinomas at 39 patients. Three patients with negative biopsies were
      incidentally diagnosed at TURP. Average age of treated patients was 72 years (51
      90), with Gleason score 6.12 and PSA average 32.4 (5.2-159). Ten radical
      prostatectomies, 23 subcapsular orchidectomies and 6 chemical castrations by LH
      RH agonists were made. Further palliative irradiation was performed in 7 patients
      with bone metastases and radical irradiation in 16 patients unable to undergone
      surgery. Only early detection of disease can lead to successful treatment, so we
      should search for prostate tumor in all male patients who come to see urologist
      and are older than 50 years.

PMID- 16808095
TI  - [Microcellular lung carcinoma in patient with hepatosplenic T-cell lymphoma: a
      case report].
AB  - Hepatosplenic T-cell lymphoma (HSTCL) is a rare form of extranodal non-Hodgkin
      lymphoma derived from cytotoxic T-cells, usually manifesting by sinusoidal
      infiltration of spleen, liver and bone marrow. In 1997 World Health Organization
      classified malignant lymphomas and placed HSTCL among peripheral T-cell
      neoplasms. The course of the diseases is usually very agressive with a median
      survival time of 8 to 16 moths despite multiagent chemotherapy. We present a case
      of a 48-year-old male patient whose initial symptoms were fatigue, weight loss
      and night sweats, which were followed by splenomegaly and pancytopenia. After
      clinical examination we suspected him to have HSTCL which was proved
      pathohistologically upon splenectomy and it is the first case of this lymphoma
      diagnosed in "Merkur" Clinical Hospital. As a first line of lymphoma therapy we
      decided to apply FED course (fludarabine, cyclophosphamide, prednisone), being
      aware of the published poor results the standard CHOP chemotherapy
      (cyclophosphamide, doxorubicin, vincristine, prednisolone) yields. As far as we
      know, the results of this chemotherapy course in the therapy of this tumor have
      never been published. The patient underwent 6 courses of FED therapy, which he
      tolerated well and was in good clinical condition. Upon the completion of the 6th
      course of therapy he was diagnosed with lung anaplastic microcellular carcinoma
      and was treated with 3 course of PE therapy (cisplatin, etoposide).

PMID- 16808096
TI  - [Magnetic resonance imaging in fetal medicine].
AB  - Fast magnetic resonance imaging (MRI) has revolutionized our ability to image the
      fetus by using fast scanning techniques. Individual images are obtained in 300
      400 s allowing fetal imaging without sedation due to reduced fetal movement
      artifacts. MRI is most useful for evaluation of the anomalies of fetal nervous
      and urinary system which are not fully clarified by ultrasound. The influence of
      magnetic resonance depending on gestational age on perinatal management nowadays
      is certain. This review discusses its current application and future
      developments.

PMID- 16808097
TI  - [Laparoscopic treatment of acute cholecystitis].
AB  - Acute cholecystitis has been considered a contraindication for laparoscopic
      cholecystectomy after its affirmation as the golden standard for treatment of
      chronic cholecystitis. However, over time it has been proven that acute
      cholecystitis could also be managed laparoscopically, although it was technically
      demanding procedure, burdened with relatively high conversion rates. In this
      study we present our series of 26 patients, urgently admitted for acute
      cholecystitis. They are presented with clinical findings typical for acute
      cholecystitis. The diagnosis was determined using ultrasound examination, and
      confirmed postoperatively by pathohistological findings. In all 26 cases we
      managed to perform laparoscopic cholecystectomy, there were no conversion. Mean
      operative time was 73 +/- 21 minutes. Postoperatively, we haven't recorded any
      significant complications. Mean hospital stay was 4.8 +/- 2.5 days. Even though
      laparoscopic treatment of acute cholecystitis is technically more demanding and
      lengthier procedure than laparoscopic treatment of chronic cholecystitis, we
      consider acute cholecystitis to be a laparoscopically manageable disease. During
      the operation, tissue edema and hyperemia presented main technical challenge.
      They presented a significantly greater problem if the symptoms lasted for more
      than 3 days prior to operation. Therefore we suggest that laparoscopic
      cholecystectomy should be carried out in the first 72 hours after the onset of
      symptoms, since any further delay will lead to development of tissue hyperemia
      and edema, thus making the operation technically more demanding.

PMID- 16808098
TI  - [Pathophysiology of ischaemia-reperfusion injury].
AB  - Reperfusion of ischaemic tissue provides oxygen and substrates that are necessary
      for tissue recovery and concurrently removes toxic metabolites. However,
      reperfusion may induce various detrimental processes that may cause further
      tissue damage. Such deterioration of tissue function after reperfusion is defined
      as ischaemia-reperfusion injury. The consequences of ischemia-reperfusion injury
      vary from reversible cell dysfunction to local and remote tissue destruction,
      multiple organ failure and death. The pathogenesis of ischaemia-reperfusion
      injury is complex and includes excessive production of reactive oxygen species,
      activation of neutrophils, activation of complement, involvement of cytokines and
      other inflammatory mediators, vasoactive substances NO and endothelin. This
      review discusses the pathophysiology of ischaemia-reperfusion injury, the
      mechanisms of reactive oxygen species production, and the role of other factors
      in the pathogenesis of such injury. Several approaches and procedures used in pre
      clinical and clinical studies in order to limit ischaemia-reperfusion injury are
      also presented.

PMID- 16808099
TI  - [The role of genetic factors in the etiopathogenesis of psoriasis].
AB  - Psoriasis is a chronic skin disease characterized by epidermal hyperproliferation
      that is probably mediated by an immunologic reaction to particular epidermal,
      dermal or circulating immunogenic peptide. The inheritance of psoriasis within
      some families suggests the importance of genetic factors in the pathogenesis of
      the disease. Population based studies revealed that psoriasis is associated with
      HLA genes class I and II located on the chromosome 6. The highest risk of
      developing psoriasis carries the HLA-Cw*0602 gene. The analysis of HLA
      polymorphism in Croatian patients also showed the importance of Cw*0602 allele in
      psoriasis susceptibility. Until now, eight different gene loci for psoriasis are
      mentioned in the OMIM (Online Mendelian Inheritance in Men) data base. Even
      though, the psoriasis association with HLA genes is doubtless, only some carriers
      of susceptible genes develop the disease. Therefore, some other genes except HLA
      genes as well as some environmental factors have a role in the pathogenesis of
      psoriasis.

PMID- 16808100
TI  - [Alternative hormone therapy in postmenopause].
AB  - Despite the fact that hormonal combination used in huge Wpmen's Health Initiative
      (WHI) is not common all over the world, and treated population is, because of
      age, in risk per se, study results have consternated not only lay users, but
      prescribers too. Namely, increased cancer, stroke and coronary heart disease risk
      associated with long term use of postmenopausal hormone therapy (HT) have rapidly
      declined the number of women treated with HT (either estrogen alone or estrogen
      plus progestogen). Considering recent position statements from leading
      organizations dealing with menopause, individualization of therapy and lower
      dosage HT becomes the state of the art. Not only WHI, but also results of other
      studies published during past few years, have induced curiosity for non-estrogen
      containing treatments in climacteric medicine. This review shows not only
      mandatory list of possibilities, but also emphasises which of the alternative and
      complementary treatments are evidence based regarding published randomized
      controlled trials.

PMID- 16808101
TI  - [Sodium levels in the Dalmatian water resources in 2003].
AB  - The objective of this paper was to analyse the sodium levels in the spring water,
      surface and groundwater in Dalmatia during 2003. The sodium concentrations were
      computed from the difference between coefficient K1 (the ratio between the
      chlorides and sulfates sum and the carbonate hardness) and K2 (the ratio between
      non-carbonate and carbonate hardness) and carbonate hardness. The average sodium
      concentrations have been expressed by a median and they ranged from 1.8 mg/L Na
      to 17.6 mg/L Na in the spring water, in the surface water they ranged from 1.0 to
      502 mg/L Na and in the groundwater they ranged from 11.1 mg/L Na to 124.3 mg/L
      Na. In the spring water the sodium concentrations varied from 32% to 217%, in the
      surface water from 40% to 159% and in the groundwater from 77.3% to 180%.
      According to the corrosiveness coefficient K1, 83% of the spring waters are
      classified as non-corrosive and 17% as water with a low degree of corrosiveness;
      84% of the surface waters are classified as non-corrosive water and 16% as very
      corrosive; all groundwater is classified as very corrosive water. Out of the
      total of 60 analyzed water resources 64% are classified as hypotensive, 20% as
      normotensive and 17% as hypertensive water. The drinking water has been defined
      as hypotensive (<10 mg/L Na), normotensive (from 11 to 20 mg/L Na) and
      hypertensive (>20 mg/L Na) by relating the sodium concentration projectively with
      the notion of arterial pressure knowing that an increased sodium concentration in
      blood increases the blood pressure. From the informatics standpoint the data
      related to health should be classified into data bases which can serve as a
      methodological starting point for studying the influence of sodium upon human
      health. Consequently, epidemiological studies should relate various sodium levels
      in drinking water to other factors which affect human health.

PMID- 16808102
TI  - [Women and medical skill--historic view].
AB  - By the Banal edict of 28 June 1903, while the country was part of the Austrian
      Hungarian monarchy, women physicians in Croatia were granted permission to carry
      out medical practice. In the memory of that occasion a historical overview of the
      women's role in medical science and practice is presented. The evidence of
      women's medical skills dates back to 2500 BC in Ancient Egypt. The 11th and 12th
      centuries saw first women gain access to medical schools in Europe. Women doctors
      practiced mainly gynaecology, obstetrics, cosmetics, skin and eye diseases. It
      took another seven centuries for them to be treated as men's equals as far as
      medical training and permission to work were concerned. In the 18th and 19th
      centuries the number of female physicians greatly increased in Europe, USA, and
      Canada. In Croatia the first woman medical doctor was Milica Sviglin Cavov, who
      graduated from the Medical School in Zurich in 1893, but was not allowed to work
      in the home country. The first woman to practice medicine in Croatia was Karola
      Maier Milobar in 1906. The first woman to have graduated from the Medical School
      in Zagreb, capital of Croatia, following its opening in 1917, was Kornelija
      Sertic The paper concludes with a view of the present-day role of women in
      medical practice, education and science.

PMID- 16808103
TI  - [Role of clinicians in cytologic diagnosis].

PMID- 16808105
TI  - Reproduction ofarticulator settings and movements with an ultrasonic jaw movement
      recorder.
AB  - The KaVo ARCUS digma is an ultrasonic mandibular movement recorder, which
      provides articulator setting information for Kavo articulators. The first part of
      this study examined the ability of the device to record condylar control values
      pre-set on Kavo's own articulators. Using a mechanical pantograph, the second
      part of the study tested the ability of the device to record, and then allow
      reproduction on a Kavo articulator, the movements of a Denar D5A articulator. The
      device was accurate in recording Sagittal Condylar Inclination, but less so for
      Progressive Side Shift. Immediate Side Shift was persistently under-recorded.
      Pantographic tracings demonstrated similar paths of articulator movements so long
      as Immediate Side Shift was not set.

PMID- 16808104
TI  - The effect of disinfection on irreversible hydrocolloid and type III gypsum
      casts.
AB  - Under standardised conditions, 80 impressions were made of a ruled stainless
      steel die (ISO Specification 1563) using irreversible hydrocolloid (alginate).
      The alginates were subsequently treated with 3 commercially available
      disinfectants, Perform-ID, ImpressiVand Dimenol and poured with type III gypsum.
      The alginates were evaluated for surface detail reproduction and the gypsum for
      surface detail reproduction and hardness. Disinfection with Perform ID
      significantly affected the surface detail reproduction of alginate while Dimenol
      and ImpressiV did not. Perform ID and Dimenol both significantly affect the
      hardness of poured type III gypsum casts while ImpressiV did not.

PMID- 16808106
TI  - Abutment taper of full cast crown preparations by dental students in the UWI
      School of Dentistry.
AB  - Retention of crowns has been shown to be inversely proportional to taper. The
      objective of this study was to compare the abutment taper of teeth prepared for
      full veneer crowns by students at the UWI School of Dentistry with those of other
      dental schools. Twenty five dies were scanned by a Co-ordinate Measuring Machine
      (CMM) and the mean taper and standard deviations were found to be 20.3 +/- 11.3
      degrees mesio-distally and 18.3 +/- 8.5 degrees bucco-lingually. This study shows
      that the taper achieved by dental students at the UWI School of Dentistry
      preparing teeth for full veneer crowns is comparable to those achieved by other
      dental students in the US, UK, Europe and Japan.

PMID- 16808107
TI  - The effect of a commercially available chlorhexidine mouthwash product on human
      osteoblast cells.
AB  - Chlorhexidine mouthwash (CMW) is used for decontamination of tooth, implant or
      prosthetic surfaces to treat or prevent local infection. A cell culture model was
      used to investigate cytotoxicity of CMW employing an MTT assay to record cell
      activity. Human osteoblast-like cells (HOS TE 85) were seeded. Dilutions of CMW
      (1:1 to 1:128) were made up with culture medium. Positive and negative controls
      were prepared. Cells were incubated, exposed to CMW, for 5 min to 4 h. Diluted
      tetrazolium salt solution was added. Plates were incubated for a further 4 h.
      Medium was removed, dimethylsulphoxide was added, and absorbance at 570nm read.
      Undiluted CMW caused total cytotoxicity, similar to positive control. Progessive
      dilution of CMW was associated with elevated cell survival. Cytotoxicity
      increased with longer time exposures. It was concluded that CMW can be cytotoxic
      in high concentrations and when applied for long time periods. Work is needed to
      determine effects on other cell types and clinical significance of these
      findings.

PMID- 16808108
TI  - Influence of surface treatments on the shear bond strength of Panavia 21 to a
      Type III gold alloy.
AB  - Cylinders of Type III gold alloy were sandblasted with either: 50 micron
      Aluminium Oxide particles (Group 1); CoJet Sand (Group 2); the CoJet System -
      CoJet Sand followed by application of silane primer (Group 3). Shear testing was
      undertaken following apposition of Panavia 21 resin. Mean shear bond strengths
      (+/- standard deviation) were Group 1, 32.9 (+/-18.2) MPa; Group 2, 26.5 (+/
      10.8) MPa and Group 3, 45.6 (+/- 25.8) MPa. There was no statistically difference
      between Group 1 and 2; and between group 1 and 3. However, there was a
      significant; difference between Group 2 and 3 p < 0.05). While the CoJet System
      achieved the highest mean shear bond strength it conveyed no statistical
      advantage over the traditional method of sandblasting with aluminium oxide.

PMID- 16808109
TI  - A technique for post-orthodontic retention of maxillary anterior teeth in the
      restored dentition: A case report.
AB  - Retention is one of the most important factors in the long term success of
      orthodontic treatment. In the adult patient when orthodontic movement is part of
      an overall treatment plan involving other disciplines, the provision of permanent
      retention can he complicated. Several methods have been proposed in the
      literature to date, all with their own problems and risks. This case report
      presents a technique that may solve this problem for suitable patients in a way
      that is both non-invasive and has excellent long-term maintenance potential.

PMID- 16808110
TI  - Clinical marginal gap of porcelain fused to electro-formed gold coping crowns.
AB  - This study evaluated the marginal and internal gaps of Auro Galvano Crowns (AGC)
      in vivo. One hundred AGC crowns were examined using white and black silicone
      materials; the thickness of the silicone layer was measured at 16 reference
      points using a microscope. The mean marginal gaps among anterior, premolar and
      molar teeth, and the mean gaps within the groups were compared by analysis of
      variance and Dunnett T3 test. The results showed that at the margins, there were
      no significant differences among the four measuring points within each group, and
      there were no significant differences in the mean marginal gaps among the three
      groups. The mean marginal gaps in all groups were within the limits of clinical
      acceptability.

PMID- 16808111
TI  - Dental implant treatment for patients with psychiatric disorders.
AB  - The literature with respect to whether or not psychiatric disorders represent a
      contraindication to dental implant treatment is sparse and contradictory. This
      paper describes three cases in which patients with psychiatric disorders were
      provided with dental implant retained prostheses. It is concluded that mental
      health disorders are not necessarily a contraindication to dental implant
      treatment and dental implant treatment can provide valuable psychological
      support. If any doubt exists about the effect of a psychiatric disorder on the
      prognosis of implant treatment the opinion of a psychiatrist should be obtained.
      The development of liaison psychiatry for dental hospitals should be seen as an
      ideal.

PMID- 16808112
TI  - Probiotics and their potential health claims.
AB  - Many studies have attempted to identify specific positive health effects of
      probiotics. One of the challenges in generalizing health effects of probiotics is
      that different strains exert disparate effects on human health. As a result, the
      efficacy of one strain or species cannot necessarily be inferred from another.
      The objective of this review is to examine the current scientific literature that
      could be used as the basis for potential health claims. More specifically, this
      paper will review existing evidence of different probiotic strains to prevent and
      treat diarrhea, treat irritable bowel syndrome (IBS), treat inflammatory bowel
      disease, and prevent colon cancer. The strongest evidence is related to the use
      of Lactobacillus rhamnosus GG in the prevention and treatment of rotavirus
      associated diarrhea. Further examination of the literature also shows promise in
      the treatment of some forms of IBS with probiotics. Future studies that use
      consistent supplementation regimes will allow more definitive conclusions to be
      drawn on the effects of probiotics on IBS, inflammatory bowel disease, and colon
      cancer.

PMID- 16808113
TI  - The elimination of trans fats from spreads: how science helped to turn an
      industry around.
AB  - Mensink and Katan showed in 1990 that trans fats reduce high- and increase low
      density lipoprotein cholesterol. Unilever aided this study because the company
      considered knowledge on trans fats incomplete in spite of their long history of
      safe use. The decision in 1994 to remove trans fats from Unilever's retail
      spreads was triggered by media events, but it was built on a solid understanding
      of the nutritional and technological aspects of trans fats. Over the next 14
      years, manufacturers worldwide followed suit. This experience illustrates that
      food companies need to know about the health effects of their products and how to
      apply that knowledge.

PMID- 16808114
TI  - Nutrition and genes in the development of orofacial clefting.
AB  - Clefts of the lip, alveolus, and/or palate, which are called orofacial clefts
      (OFC), occur in 0.5 to 3 per 1000 live and stillbirths. The pathogenesis of these
      congenital malformations remains largely unknown, but evidence is increasing that
      both nutritional and genetic factors are involved. Unlike genetic factors,
      nutritional causes can be corrected and may therefore contribute to the
      prevention of OFC. The goal of this review is to summarize the embryogenesis and
      genes involved in OFC, and to give an overview of the nutrients and related genes
      in humans. Improving our knowledge of the role of nutrition, genes, and their
      interactions in the pathogenesis of OFC may stimulate the development of
      nutritional interventions for OFC prevention in the future.

PMID- 16808115
TI  - The FOOD Trial Collaboration: nutritional supplementation strategies and acute
      stroke outcome.
AB  - Results from three large, randomized, multicenter FOOD (Feed or Ordinary Food)
      Collaboration Trials showed no reduction in death or poor outcome with routine
      oral protein-energy supplementation of stroke patients who were primarily well
      nourished upon admission to the hospital. Nasogastric tube feeding was favored
      over percutaneous endoscopic gastrostomy as the early route of feeding in
      dysphagic stroke patients.

PMID- 16808116
TI  - How an increased intake of alpha-tocopherol can suppress the bioavailability of
      gamma-tocopherol.
AB  - alpha-Tocopherol is the only form of vitamin E in vitamin supplements, whereas
      gamma-tocopherol is the predominant form of vitamin E in the US diet. gamma
      Tocopherol has beneficial properties as an anti-inflammatory and possibly anti
      atherogenic and anticancer agent. Excess a-tocopherol taken in supplements causes
      a reduction of gamma-tocopherol concentration in plasma. The biochemical
      mechanism of this effect, which is important to human nutrition, has recently
      been elucidated.

PMID- 16808117
TI  - Management of unconscious casualties in far forward deployed Special Forces.

PMID- 16808118
TI  - Cardiovascular risks in a military health care beneficiary population with high
      blood pressure.

PMID- 16808119
TI  - Cigarette smoking among enlisted military personnel during deployment.

PMID- 16808120
TI  - Body composition standards to prevent obesity in the military.

PMID- 16808121
TI  - Training for medical support of mountain operations.
AB  - Man is not designed to live or to fight at altitude, and mountains have
      successfully resisted armies' attempts to conquer them for centuries. High
      altitude mountainous terrain imposes great strains on individuals, units, and the
      health services designed to protect them. Medical personnel are challenged to
      minimize the damaging effects of the harsh environment, to maximize survival
      rates, and to preserve combat effectiveness by optimizing physiological and
      behavioral adaptation. Such challenges are best met with targeted medical
      training. This article reviews basic altitude physiology, relevant military
      history, the scope of altitude illnesses, prevention and treatment strategies,
      and existing mountain medicine training programs.

PMID- 16808122
TI  - Night firing range performance following photorefractive keratectomy and laser in
      situ keratomileusis.
AB  - OBJECTIVE: To investigate the effect of laser refractive surgery on night weapons
      firing. METHODS: Firing range performance was measured at baseline and
      postoperatively following photorefractive keratectomy and laser in situ
      keratomileusis. Subjects fired the M-16A2 rifle with night vision goggles (NVG)
      at starlight, and with iron sight (simulated dusk). Scores, before and after
      surgery, were compared for both conditions. RESULTS: No subject was able to
      acquire the target using iron sight without correction before surgery. After
      surgery, the scores without correction (95.9 +/- 4.7) matched the preoperative
      scores with correction (94.3 +/- 4.0; p = 0.324). Uncorrected NVG scores after
      surgery (96.4 +/- 3.1) exceeded the corrected scores before surgery (91.4 +/-
      10.2), but this trend was not statistically significant (p = 0.063). CONCLUSION:
      Night weapon firing with both the iron sight and the NVG sight improved after
      surgery. This study supports the operational benefits of refractive surgery in
      the military.

PMID- 16808123
TI  - Factory-based permethrin impregnation of uniforms: residual activity against
      Aedes aegypti and Ixodes ricinus in battle dress uniforms worn under field
      conditions, and cross-contamination during the laundering and storage process.
AB  - The factory-based permethrin coating technique has only recently been developed.
      Consequently, no data are available on residual activity, laundering, and
      weathering resistance in impregnated battle dress uniforms (BDUs) worn under
      military deployment conditions, or on the cross-contamination potential of such
      uniforms. Herein, factory-impregnated BDUs worn-out during military deployment to
      Afghanistan were investigated for residual permethrin concentration, residual
      efficacy against arthropod vectors, and cross-contamination during laundering and
      storage. When compared with BDUs subjected to 50 defined washings using the U.S.
      Insect/Arthropod Repellent Fabric Treatment method, no significant differences in
      efficacy were observed against Aedes mosquitoes, but remaining knockdown activity
      in Ixodes ticks was significantly better in polymer-coated BDUs. BDUs impregnated
      by the polymer-coating method were found to be effective for the life of the
      uniform, ensuring protection of soldiers in the field from arthropod vectors,
      while causing less cross-contamination than those treated by the Insect/Arthropod
      Repellent Fabric Treatment method.

PMID- 16808124
TI  - Chest pain among combat veterans: a conceptual framework.
AB  - This article describes the decision-making processes regarding seeking treatment
      for the symptom of chest pain in a population of combat veterans with post
      traumatic stress disorder and panic disorder. Qualitative methods and
      standardized tools were used to explore the prehospital experiences of combat
      veterans who met diagnostic criteria for post-traumatic stress disorder, panic
      disorder, and admission to a coronary care unit for the symptom of chest pain.
      Semistructured audiotaped interviews were conducted. Obtaining medical treatment
      for the chest pain was dependent on internal and external motivating forces
      outweighing internal and external restraining forces in the decision-making
      process. The experience of military training influenced responses because of the
      expectation of self-reliance. A conceptual model emerged from the data that
      described the influences and restraints in seeking medical treatment.

PMID- 16808125
TI  - Ketamine for procedural sedation and analgesia by nonanesthesiologists in the
      field: a review for military health care providers.
AB  - Military health care providers located in field environments frequently face
      situations in which procedural sedation and analgesia are necessary, without the
      advantage of sophisticated monitoring equipment. Ketamine is a unique agent that
      can be administered either intravenously or intramuscularly to produce
      predictable and profound analgesia, with an exceptional safety profile. We review
      the issues unique to ketamine and provide a practical guide for the use of
      ketamine for adult and pediatric patients in a field environment.

PMID- 16808126
TI  - Severe acute respiratory syndrome in a naval diver.
AB  - Severe acute respiratory syndrome (SARS) is a highly infectious, rapidly
      progressive, emerging disease. Early diagnosis and preventive measures are key
      for treatment and minimization of secondary spread. In the context of the armed
      forces, aggressive containment measures are essential to prevent an outbreak. In
      this study, we present the first reported case, to our knowledge, of SARS in a
      naval diver. The special physical requirements for divers and the potential
      complications associated with deep sea diving necessitate extensive investigation
      before certification of fitness for diving after SARS. In the early recovery
      period, potential problems during diving are caused by inadequate lung
      ventilation in relation to exercise level and increased breathing resistance
      attributable to weak respiratory muscles, with corresponding risk of hypoxia and
      hypercapnia, as well as decreased ability to respond to nonrespiratory problems
      during diving. Problems in the late recovery period include increased risk of
      diving complications (such as pulmonary barotrauma) resulting from fibrosis and
      scarring within the lung parenchyma, which are known complications of SARS. From
      our experience, we suggest that computed tomographic scans of the thorax, lung
      function tests, and careful follow-up monitoring should play a vital role in the
      assessment of patients during the convalescent period, before certification of
      fitness to dive.

PMID- 16808127
TI  - Post-traumatic shoulder dystonia in an active duty soldier.
AB  - Acquired focal dystonia is often precipitated by minor local traumatic injury,
      resulting in severe pain and disability. An active duty soldier with shoulder
      dystonia, after a fall, that responded partially to botulinum toxin A is
      described. Post-traumatic dystonia as a neurological illness is discussed, with
      emphasis on mechanisms, precipitating causes, differential diagnosis, and
      treatment implications for battlefield clinicians.

PMID- 16808128
TI  - Dermatitis artefacta in soldiers.
AB  - BACKGROUND: Dermatitis artifacta is not an uncommon disease in military settings.
      Soldiers may intentionally produce skin lesions to achieve sick leave from
      military duties. The aim of this work was to describe a series of soldiers with
      dermatitis artifacta. METHODS: A prospective study was conducted among soldiers
      of the Israel Defense Force. RESULTS: Fourteen soldiers from the Israel Defense
      Force were included in the study. There were 13 men and one woman. The ages of
      the patients ranged between 19 and 26 years. For all patients, dermatitis
      artifacta was characterized by the acute appearance of a pruritic rash located on
      readily accessible areas of the limbs and abdomen. The rash was associated with
      systemic symptoms for 12 (85.7%) of 14 patients. None of the patients admitted to
      intentionally inflicting the skin lesions. The rash consisted of erythematous
      patches with numerous papules and pustules arranged in a linear pattern. All
      patients were treated with topical corticosteroids, four patients were treated
      with antibiotics, and three patients were treated with systemic corticosteroids.
      For all patients, the eruption resolved completely within 1 to 3 weeks.
      CONCLUSIONS: In the context of soldiers standing to gain sick leave by assuming
      the sick role, dermatitis artifacta can be reliably diagnosed by noting the
      characteristic location and morphological features of the skin lesions.

PMID- 16808129
TI  - A novel device developed, tested, and used for warming and maintaining
      intravenous fluids in a forward surgical team during Operation Enduring Freedom.
AB  - OBJECTIVE: To determine whether an accessory to the Bair Hugger warming unit
      (BHWU), a piece of equipment intrinsic to the forward surgical team, could be
      designed and used to warm and to maintain large volumes of intravenous fluids at
      an optimal infusion temperature in an austere environment. METHODS: The X-1 is a
      simple, collapsible, 5-gallon nylon cooler with handles, modified with a port for
      the BHWU hose and a one-way flutter valve vent. RESULTS: The warming of
      intravenous fluids to the optimal infusion temperature was accomplished with the
      BHWU and X-1. The warming time was influenced by the ambient temperature, the
      starting temperature of the fluids, and the number of bags being warmed. The
      warmed fluid could be stored and maintained in the X-1. The heat retention of the
      fluids was influenced by the ambient temperature, the number of bags warmed, and
      the insulating properties of the X-1. CONCLUSIONS: The BHWU can be used with the
      compact X-1 to warm and to store large volumes of intravenous fluids at the
      optimal infusion temperature in the field environment and was successfully used
      by a forward surgical team in Afghanistan, during Operation Enduring Freedom, for
      the treatment of combat-wounded soldiers.

PMID- 16808130
TI  - Outcomes of community-acquired, methicillin-resistant Staphylococcus aureus, soft
      tissue infections treated with antibiotics other than vancomycin.
AB  - Community-acquired, methicillin-resistant Staphylococcus aureus (cMRSA), soft
      tissue infections are becoming increasingly prevalent in the outpatient setting.
      Few studies have been specifically designed to examine the efficacy of oral
      antibiotic therapy for these infections. We performed an observational study to
      determine the effect of alternative, orally administered antibiotics on cMRSA
      soft tissue infections. Consecutive patients between January 2001 and March 2004
      who had skin or soft tissue infections from which cMRSA was isolated and who had
      never received vancomycin were studied through retrospective and concurrent
      review. Primary outcome measures were improvement or resolution of infection 5
      and 14 days after initiation of treatment with orally administered antibiotics
      and rates of recurrence within 30 days after completion of treatment. Thirty
      subjects met the inclusion criteria. Twenty-one subjects received either
      clindamycin, trimethoprim/sulfamethoxazole, doxycycline/minocycline, or a
      fluoroquinolone. Five subjects received a beta-lactam antibiotic with abscess
      drainage, and four subjects underwent abscess drainage alone. Improvement was
      noted for all subjects at 5 days, complete resolution of infection occurred for
      all subjects by 14 to 17 days, and in no case did relapse occur within 30 days.
      cMRSA skin and soft tissue infections can be successfully treated with orally
      administered antibiotics to which the organism has demonstrable in vitro
      susceptibility.

PMID- 16808131
TI  - Fetal growth curves for an ethnically diverse military population: the American
      Institute of Ultrasound in Medicine-accredited platform experience.
AB  - OBJECTIVE: To determine which fetal growth curve provided the best estimates of
      fetal weight for a cohort of ethnically diverse patients at sea level. METHODS:
      The study consisted of a population of 1,729 fetuses examined at sea level
      between January 1, 1997, and June 30, 2000, at 18 weeks, 28 weeks, and term.
      Gestational age (GA) based on menstrual dates was confirmed or adjusted by crown
      rump length or early second-trimester biometry. Fetal weight was estimated by
      using biparietal diameter, head circumference, abdominal circumference, and femur
      length. Our fetal growth curves were analyzed with fourth-order polynomial
      regression analysis, applying four previously defined formulae for fetal growth.
      RESULTS: Fetal growth curves for estimated fetal weight demonstrated the expected
      parabolic shape, which varied according to the formulae used. Our curve best fit
      the following equation: estimated fetal weight = 4.522 - 0.22 x GA age + 0.25 x
      GA(2) - 0.001 x GA(3) + 5.248 x 10(-6) x GA(4) (R2 = 0.976). SD increased in
      concordance with GA. CONCLUSION: Madigan Army Medical Center serves a racially
      mixed, culturally diverse, military community with unrestricted access to
      prenatal care. Determination of the optimal population-appropriate growth curve
      at the correct GA assists clinicians in identifying fetuses at risk for growth
      restriction or macrosomia and therefore at risk for increased perinatal morbidity
      and death.

PMID- 16808132
TI  - Hypercholesterolemia and smoking habits of Lithuanian military personnel.
AB  - OBJECTIVE: To investigate the prevalence of risk factors for cardiovascular
      disease, namely, hypercholesterolemia and current smoking, among 25- to 54-year
      old men and women among Lithuanian active duty military personnel. METHODS: Serum
      cholesterol levels were measured enzymatically for 200 persons (126 men and 74
      women). Interviews regarding smoking habits were performed for 82.5% of those
      persons (98 men and 67 women). RESULTS: Hypercholesterolemia (total cholesterol
      level of > or = 6.2 mmol/L) was determined for 45.2% of men and 40.5% of women.
      After distribution of men and women into three age groups (25-34, 35-44, and 45
      54 years), it was determined that the rate of hypercholesterolemia increased with
      age (among groups of men, 29.6%, 46.7%, and 74.0%; among groups of women, 18.8%,
      51.5%, and 40.0%, respectively). The proportion of current smokers among men was
      2.6 times higher than that among women (45.9% vs. 17.9%; p < 0.001). The highest
      rate of current smoking was in the 35- to 44-year group of men (64.5%). The
      coexistence of hypercholesterolemia and current smoking among men was 3.1 times
      higher than that among women (23.5% vs. 7.5%; p < 0.01). The highest rates of
      current smoking with hypercholesterolemia were in the 35- to 44-year and 45- to
      54-year groups of men (32.2% and 31.8%, respectively). CONCLUSION: The data
      demonstrated a relatively high rate (32.1%) of coexistence of two independent
      risk factors for cardiovascular disease (hypercholesterolemia and current
      smoking) among men 35 to 54 years of age from Lithuanian military personnel.

PMID- 16808133
TI  - A survey of mild traumatic brain injury treatment in the emergency room and
      primary care medical clinics.
AB  - This study surveyed health care providers about their evaluation and treatment of
      mild traumatic brain injury (TBI) in adults. We presented two vignettes
      describing mild TBI cases to staff in the emergency department (N = 22) and
      primary care clinics (N = 16) at Wilford Hall Air Force Medical Center and asked
      how they would evaluate and treat these patients. Most providers said they would
      assess visual changes, nausea/vomiting, headache, and neck pain. More emergency
      department personnel than primary care clinic providers would make referrals to
      different specialties, whereas more primary care clinic providers would schedule
      a follow-up appointment. Neither group of providers mentioned assessing common
      postconcussive symptoms of fatigue, emotional changes, and problems sleeping.
      Comparing findings to current literature suggest that added focus on emotional,
      cognitive and psychosocial factors, and education of the patient and family could
      improve early identification of mild TBI patients at risk for poor recovery.

PMID- 16808134
TI  - Comparison of injury rates between cadets with limb length inequalities and
      matched control subjects over 1 year of military training and athletic
      participation.
AB  - OBJECTIVES: To compare lower-limb overuse injury and low back pain incidence
      among cadets with and without limb length inequality (LLI) over 1 year of
      military training and athletic participation. METHODS: A total of 1,100 cadets
      were screened for LLIs; 126 of 1,100 were identified to have a LLI of > 0.5 cm
      and were assigned a matched control cadet. Injury rates, numbers of visits to
      sick call, and numbers of days spent on medical excusal during a 1-year period
      were then compared for the 252 cadets. RESULTS: There was no difference in
      prevalence of injury between the groups and no significant differences (p > 0.05)
      between the groups in injury rates, visits to sick call, or number of days spent
      on medical excusal. CONCLUSIONS: These findings do not support any increased
      incidence of injuries in a young, healthy, athletic, military population with
      mild LLIs, compared with matched control subjects without LLIs, over 1 year.

PMID- 16808135
TI  - The prevalence of admission for sarcoma in the military health system during 2002
      2003.
AB  - The etiology of sarcomas is not clear. Environmental exposures have been
      implicated as potential agents in the development of some sarcomas, but more
      research is needed. The military health system (MHS) may be able to provide
      population-based information regarding sarcomas. Discharge diagnoses for bone
      sarcoma and soft tissue sarcoma were searched within a large administrative
      database maintained by the U.S. military. There were > 200 cases of bone sarcoma
      and > 300 cases of soft tissue sarcoma during the 2-year study period of 2002
      2003. The crude prevalence of admission for bone sarcoma within the MHS was 1.2
      cases per 100,000 per year. The crude prevalence of admission for soft tissue
      sarcoma was 1.7 cases per 100,000 per year. These statistics suggest that the MHS
      may be used to test hypotheses regarding sarcoma epidemiological features,
      especially for studies that concern military-related exposures. However, nearly
      70% of the military beneficiaries who were sarcoma patients were admitted to
      civilian hospitals, as opposed to military treatment facilities. Therefore,
      population-based studies of sarcoma patients in the MHS should seek means to
      capture data for patients who are treated outside military facilities. The
      database used for this study may provide important information regarding these
      patients. In addition, military health care planners may use the information from
      this study to develop referral strategies within the MHS.

PMID- 16808136
TI  - Endoscopy in a deployed combat support hospital: maintaining military end
      strength.
AB  - OBJECTIVE: The objective was to examine the safety and efficacy of the 48th
      Combat Support Hospital's use of diagnostic endoscopy in Afghanistan. METHODS: A
      retrospective review was performed on the medical records of all endoscopy
      patients treated at the 48th Combat Support Hospital in Bagram, Afghanistan, from
      December 6, 2002 through June 7, 2003. RESULTS: Twenty-four patients (male, 21;
      female, 3; mean age, 35 years) underwent 28 endoscopic procedures as follows:
      colonoscopy, 14; esophagogastroduodenoscopy (EGD), 13; and flexible
      sigmoidoscopy, 1. Four patients underwent both EGD and colonoscopy. There were no
      complications. Of the 18 U.S. military patients, 3 (15%) were evacuated for
      further evaluation and/or treatment and 1 (5%) patient underwent an elective
      screening colonoscopy. For 14 of 17 U.S. military personnel (82%), the endoscopic
      procedures obviated evacuation from Afghanistan. CONCLUSIONS: Diagnostic
      colonoscopy and EGD were valuable and safe adjuncts that precluded evacuations
      out of theater for 82% of military patients. Endoscopy should be used when U.S.
      military operations necessitate the deployment of large numbers of forces for
      protracted periods.

PMID- 16808137
TI  - Effects of pregnancy on the Army Physical Fitness Test.
AB  - The purpose of this study was to determine the amount of time needed for
      postpartum soldiers to return to prepregnancy fitness condition as evidenced by
      Army Physical Fitness Test scores (APFT). The findings from this study have
      implications for health care providers, patients, and the Army regarding the
      effects of pregnancy and delivery on the human body, and determining the actual
      and perceived time needed for postpartum recovery and return to prepregnancy
      fitness condition. Using a quantitative descriptive design, data were gathered
      using a questionnaire. Results revealed that complications, weight gain, and
      postpartum exercise practices had statistically significant effects on postpartum
      APFT scores. There were statistically significant differences between the
      prepregnancy and first postpregnancy APFT scores as well. The significant
      differences in scores and personal beliefs stated by the soldiers suggest that
      the current pregnancy profile of 6 months is not enough time for women to recover
      and perform as they previously did.

PMID- 16808138
TI  - Brief interventions to reduce harmful alcohol use among military personnel:
      lessons learned from the civilian experience.
AB  - Unhealthy alcohol use is among the leading causes of morbidity and mortality in
      the United States. Among military personnel, service members between the ages 18
      and 25 had a 27.3% prevalence of heavy drinking in the previous 30 days, compared
      to 15.3% among civilians in the same age group. In the civilian world, > 100
      million patients are treated in U.S. emergency departments (ED) annually; 7.9% of
      these visits are alcohol related. Alcohol is associated with a broad range of
      health consequences that may ultimately present in the ED setting: traumatic
      injuries (e.g., motor vehicle crashes, intentional violence, falls);
      environmental injuries (e.g., frostbite); cardiovascular problems (e.g.,
      hypertension, dilated cardiomyopathy); gastrointestinal disorders (e.g.,
      hepatitis, pancreatitis, gastrointestinal bleeding); neurological problems (e.g.,
      encephalopathy, alcohol withdrawal, withdrawal seizures), as well as
      psychological problems (e.g., depression, suicide). Seminal work has been done to
      create behavioral interventions for at-risk drinkers. These motivational
      interventions have been found to be successful in encouraging clients to change
      their risky behaviors. We present such a technique, called the Brief Negotiated
      Interview as performed in a civilian ED setting, in hopes of adapting it for use
      in the military context. Military health care providers could easily adapt this
      technique to help reduce risky levels of alcohol consumption among service
      members, retirees, or military dependents.

PMID- 16808139
TI  - The health readiness of junior enlisted military women: the social determinants
      of health model and research questions.
AB  - Currently, women comprise 17% of the 1.4 million U.S. active military and 20% of
      the 1.2 million reserve force. Well over three-quarters of these women are
      enlisted (82%). Enlisted women are young, between the ages of 17 and 29, and one
      half are ethnic minorities. Enlisted women are a growing minority within the
      predominantly male hierarchical military organization. The most junior of these
      women, in addition to being vastly outnumbered by men, fall along with junior
      enlisted men at the bottom of the military organizational structure. This unique
      position may have health consequences. The purpose of this article is to propose
      research questions within the context of the Marmot and Wilkinson's social
      determinants of health model. Proposed research questions are provided to address
      the current gaps in the science related to the contextual health readiness issues
      of junior enlisted military women.

PMID- 16808140
TI  - The importance of body weight and weight management for military personnel.
AB  - Weight or fat reduction and maintenance among military personnel and attainment
      of desired body composition and physical appearance are considered important. A
      high level of body fat has been shown to have an adverse effect on performance in
      a number of military activities. The effect of rapid weight loss on performance
      appears to depend on the method of weight loss, the magnitude of weight loss, and
      the type of exercise or activity performance test used. Personnel who undertake
      imprudent weight-loss strategies, that is, personnel who try to change their
      usual body size by chronically restricting their food and fluid intake, may
      suffer a number of problems. Overweight personnel and their military coaches are
      just as susceptible to false ideas about weight loss and dieting as the rest of
      the community. Inappropriate weight loss causes a loss of lean tissue and can
      reduce, rather than enhance, performance. The understanding and promotion of
      safe, effective, appropriate weight-loss and weight-maintenance strategies
      represent important functions of the military system and officials. The greatest
      likelihood of success requires an integrated program, both during and after the
      weight-loss phase, in which assessment, increased energy expenditure through
      exercise and other daily activities, energy intake reduction, nutrition
      education, lifestyle changes, environmental changes, and psychological support
      are all components.

PMID- 16808141
TI  - A low-intensity intervention to prevent annual weight gain in active duty Air
      Force members.
AB  - Elevated body weight among active duty Air Force (ADAF) members is a substantial
      and growing problem, and typically results from gaining small amounts of weight
      each year over many years. We designed a strategy to prevent annual weight gain
      in ADAF members using self-directed behavior change booklets followed by weekly e
      mails about diet and physical activity for a year. The intervention was
      universally offered to ADAF members meeting selection criteria at five U.S. Air
      Force bases (n = 3,502); members at 60 other U.S. Air Force bases served as
      controls (n = 65,089). The intervention was completely effective at preventing
      weight gain in a subgroup of men (those above the lowest three ranks, with
      baseline weight above maximum allowable) and in women, while controls continued
      to gain weight. Since the intervention did not require personalized contact, this
      approach has promise for large-scale population-based efforts aimed at preventing
      weight gain in working adults.

PMID- 16808142
TI  - Health care utilization by United Nations peacekeeping veterans with co
      occurring, self-reported, post-traumatic stress disorder and depression symptoms
      versus those without.
AB  - It remains to be determined whether patients with comorbid post-traumatic stress
      disorder (PTSD) and depression use more health care resources than do those
      without. United Nations peacekeeping veterans from Canada were divided into four
      groups, i.e., PTSD alone (n = 23), depression alone (n = 167), comorbid PTSD and
      depression (n = 119), and neither (n = 164), and compared with respect to total
      number of visits to any health care professional in the past year. Analysis of
      variance revealed that the groups significantly differed in total visits. Post
      hoc analyses indicated that veterans with co-occurring PTSD and depression
      symptoms had more visits than did those in the other groups and that veterans
      with PTSD symptoms alone and depression symptoms alone had more visits than did
      those with neither PTSD nor depression. Additional analyses revealed that
      veterans with co-occurring PTSD and depression symptoms made more visits to
      general practitioners, specialists, pharmacists, and mental health professionals
      than did the others. Future research directions and implications for treatment
      planning are discussed.

PMID- 16808143
TI  - Direct admission to cardiology for patients hospitalized for atrial fibrillation
      reduces length of stay and increases guideline adherence.
AB  - OBJECTIVE: We hypothesized that a clinical pathway for inpatient management of
      atrial fibrillation on a cardiology service would result in improved resource
      utilization. METHODS: In July 2002, an evidence-based pathway was developed for
      treatment of patients hospitalized for atrial fibrillation. Guidelines directed
      patient care from admission from the emergency department to inpatient management
      on a cardiology service. Ancillary testing, anticoagulation, and inpatient length
      of stay were then compared before and after institution of the pathway. RESULTS:
      The overall length of stay was significantly shorter for patients admitted
      through the pathway (43.0 hours vs. 82.0 hours, p < 0.01). After the pathway,
      there was increased use of transesophageal echocardiography and a trend toward
      increased use of warfarin. CONCLUSIONS: Patients requiring hospitalization for
      symptomatic atrial fibrillation had a nearly 50% reduction in length of stay,
      with a trend toward increased utilization of risk-appropriate antithrombotic
      therapy, if they were directly admitted through cardiology via a clinical
      pathway.

PMID- 16808144
TI  - Chiropractic services in the Canadian Armed Forces: a pilot project.
AB  - This article reports on satisfaction associated with the introduction of
      chiropractic services within a military hospital, through a Canadian Armed Forces
      Pilot Project. We distributed a 27-item survey that inquired about demographic
      information and satisfaction with chiropractic services to 102 military personnel
      presenting for on-site chiropractic services at the Archie McCallum Hospital in
      Halifax, Nova Scotia. We provided a second 3-item survey, designed to explore
      referral patterns and satisfaction with chiropractic services, to all referring
      military physicians. A multivariable linear regression model was constructed to
      explore which factors were associated with patients' satisfaction with
      chiropractic services. The response rate to the patient and physician
      satisfaction surveys was 67.6% (69 of 102) and 83.3% (10 of 12), respectively.
      Chronic low back pain accounted for most presentations to the hospital
      chiropractic clinic. The majority of military personnel (94.2%) and referring
      physicians (80.0%) expressed satisfaction with chiropractic services. Our
      adjusted analysis found that older age (beta = -0.37; 95% confidence interval = 
      0.73 to -0.02) and a presenting complaint of knee pain (beta = -15.56; 95%
      confidence interval = -29.61 to -1.51) was associated with decreased satisfaction
      with chiropractic care. Although our finding of high satisfaction with
      chiropractic services is encouraging, formal studies on functional outcomes and
      cost effectiveness of chiropractic care are required to better inform the role of
      chiropractic services in the Canadian Armed Forces.

PMID- 16808145
TI  - Answer to last month's radiology case and image: emergency decompressive
      craniotomy with banked skull flap in subcutaneous pocket.

PMID- 16808146
TI  - Natural neo acids and neo alkanes: their analogs and derivatives.
AB  - This review presents more than 260 naturally occurring (as well as 47
      synthesized) neo fatty (carboxylic) acids, neo alkanes, and their analogs and
      derivatives, isolated and identified from plants, algae, fungi, marine
      invertebrates, and microorganisms, that demonstrate different biological
      activities. These natural metabolites are good prospects for future chemical
      preparations as antioxidants, and also as anticancer, antimicrobial, and
      antibacterial agents. Described also are some synthetic bioactive compounds
      containing a tertiary butyl group(s) that have shown high anticancer, antifungal,
      and other activities. Applications of some neo fatty (carboxylic) acid
      derivatives in cosmetic, agronomic, and pharmaceutical industries also are
      considered. This is the first review to consider naturally occurring neo fatty
      (carboxylic) acids, neo alkanes, and other metabolites containing a tertiary
      butyl group(s) [or tert-butyl unit(s)].

PMID- 16808147
TI  - Gestational diabetes mellitus enhances arachidonic and docosahexaenoic acids in
      placental phospholipids.
AB  - In previous studies, we reported that neonates of women with gestational diabetes
      mellitus (GDM) have reduced blood levels of arachidonic acid (AA) and
      docosahexaenoic acid (DHA) that were unrelated to maternal status. Since both AA
      and DHA are selectively transferred from maternal to fetal circulation by the
      placenta, we have investigated whether the FA composition of the placenta is
      altered by GDM. Thirty-six women, 11 with and 25 without GDM, were recruited from
      Newham General Hospital, London. The women with GDM had higher levels of di-homo
      gamma-linolenic (P < 0.05), docosatetraenoic (n-6 DTA; P< 0.0001),
      docosapentaenoic n-6 (P< 0.005), total n-6 (P < 0.005), docosapentaenoic (n-3
      DPA; P < 0.005), and total n-3 (P < 0.01) FA, as well as higher levels of AA (P <
      0.05) and DHA (P < 0.01), in placental choline phosphoglycerides (CPG) compared
      with the healthy women who served as controls. Similarly, the women with GDM had
      elevated n-6 DTA (P < 0.005), AA, total n-6 metabolites (P < 0.05), DHA, total n
      3 metabolites, and total n-3 FA (P < 0.005) in ethanolamine phosphoglycerides
      (EPG). In contrast to CPG and EPG, the placental TG of the women with GDM had
      higher linoleic acid (P< 0.05) and lower AA, n-6 metabolites, and n-3 DPA (P <
      0.01). The placenta is devoid of desaturase activity, and it is thought to be
      reliant on maternal circulation for both AA and DHA. Hence, the enhanced levels
      of the two FA in the placenta of the GDM group suggests that these FA are taken
      up from the maternal circulation and retained after esterification into
      phosphoglycerides instead of being transferred to the fetus. Further study is
      needed to elucidate the mechanism involved and the effect of the phenomenon on
      postnatal growth and development of the offspring.

PMID- 16808148
TI  - Effect of diacylglycerol on the development of impaired glucose tolerance in
      sucrose-fed rats.
AB  - The effects of DAG oil and TAG oil on impaired glucose tolerance in rats that
      were fed a diet containing high levels of sucrose were compared. Male Wistar rats
      (8 wk old and 32 wk old) were fed either high-sucrose (57.5% sucrose w/w) or
      control diets containing either 10% (w/w) DAG or TAG oil with a similar FA
      composition for 48 wk in 8-wk-old rats and for 24 wk in 32-wk-old rats. Plasma
      lipids, the size of the islets of Langerhans, and insulin, glucose, and
      adipocytokine levels were measured. An oral glucose tolerance test (OGTT) was
      carried out during the study period. For rats in both age groups that were fed a
      high-sucrose diet, the DAG oil group had lower plasma glucose and insulin
      response in an OGTT, and lower homeostasis model assessment-R levels, than the
      TAG oil group. Furthermore, in 8-wk-old rats that were fed a high-sucrose diet,
      the DAG oil group accumulated less visceral fat and showed suppressed decreases
      [corrected] of plasma adiponectin and [corrected] increases of plasma insulin,
      leptin, and the size of islet of Langerhans compared with the TAG oil group. No
      difference in the OGTT was found between the DAG and TAG oil groups in either age
      group of rats fed a control diet. In conclusion, these results suggest that DAG
      oil ingestion prevents the high-sucrose-diet-induced development of impaired
      glucose tolerance compared with TAG oil ingestion.

PMID- 16808150
TI  - Effect of low vitamin A status on fat deposition and fatty acid desaturation in
      beef cattle.
AB  - A group of Angus beef cattle was removed from temperate pastures and fed a very
      low beta-carotene cereal-based ration in a feedlot for over 300 d. Half the group
      was supplemented weekly with retinyl palmitate (at the rate of 60,000 IU vitamin
      A/100 live weight (LW)/day), sufficient to offset clinical vitamin A deficiency;
      the other half received no supplement. Blood was sampled from all animals at
      biweekly intervals to assess beta-carotene and vitamin A status. Adipose tissue
      was sampled by biopsy on three occasions throughout the experimental period and
      at slaughter to assess FA composition. Muscle was sampled at slaughter to
      determine the intramuscular fat content. The mean plasma concentration of beta
      carotene of all animals fell from an initial value of 20.1 to 5.2 microg/mL at 14
      d, to 1.4 microg/mL at 35 d, and to zero at 105 d. Mean vitamin A in plasma was
      not significantly different between the treatment groups initially. The values
      then rose to almost twice their initial values by 35 d, but subsequently fell to
      below initial values by day 119. Thereafter, plasma vitamin A of the supplemented
      group was significantly greater than that of the unsupplemented group (P < 0.05).
      Muscle samples at slaughter from supplemented animals contained significantly (P
      < 0.01) more intramuscular lipid (13.0 vs. 9.6%). Major changes occurred over
      time in FA composition in both groups. Saturated FA decreased as monounsaturated
      FA increased over the first 60 d. An index of desaturation of FA was
      significantly lower (P < 0.001) in the vitamin A-supplemented group than in the
      nonsupplemented group. M.P. of the adipose tissue of nonsupplemented animals was
      32.3 degrees C, significantly less (P< 0.05) than that of supplemented animals
      (34.1 degrees C). Feeding vitamin A was associated with less intramuscular fat
      but with a less desirable (less unsaturated, more solid) FA profile.

PMID- 16808149
TI  - Rat adult offspring serum lipoproteins are altered by maternal consumption of a
      liquid diet.
AB  - Palatable liquid diets for the administration of ethanol (EtOH) to animals have
      proven to be a major advance for the study of the effects of EtOH consumption
      under conditions of isocaloric nutrition of the control animals. Using a liquid
      diet, the original aim of the reported studies was to examine the effect of
      maternal EtOH consumption during pregnancy on the lipoprotein (Lp) profiles of
      the adult offspring measured by means of nuclear magnetic resonance spectroscopy.
      However, initial data suggested that compared to a maternal chow diet, the basal
      maternal liquid diet (without EtOH) had a significant effect on specific serum Lp
      of the adult offspring. The adult offspring of mothers who had consumed a basal
      liquid diet without EtOH exhibited significant increases in their plasma
      triglycerides (TG) and cholesterol content compared to adult offspring whose
      mothers consumed a chow diet. Further, there were significant increases in the
      offspring's VLDL and low density Lp (LDL) subfractions' particle number,
      regardless of whether the maternal liquid diet was ad libitum-fed, pair-fed, or
      EtOH-containing. The increase in offspring plasma TG was due to increases in
      specific VLDL subfraction particle numbers and not to increased TG content per
      particle. Similarly, the increase in plasma cholesterol was the result of
      elevated level of the very small LDL particles but not to an increased amount of
      cholesterol per LDL particle. These findings should be further examined in light
      of the widespread use of liquid diets in research to administer EtOH, especially
      for studies of fetal alcohol syndrome.

PMID- 16808152
TI  - Analysis of triacylglycerols of seeds and berries of sea buckthorn (Hippophae
      rhamnoides) of different origins by mass spectrometry and tandem mass
      spectrometry.
AB  - TAG of seeds, berries, and fruit pulp/peel of different subspecies of sea
      buckthorn (Hippophae rhamnoides) were analyzed by MS and tandem mass spectrometry
      (MS/MS). The seeds contained mainly TAG with acyl carbon number (ACN) of 52 with
      2-6 double bonds (DB) (20-30%), and TAG of ACN 54 with 3-9 DB (70-80%). In the
      pulp/peel fraction, the major TAG were species with ACN:DB of 48:1 to 48:3 (19
      49%), 50:1 to 50:4 (31-41%), and 52:1 to 52:6 (9-19%). The molecular weight
      species of whole berries largely resembled those of fruit pulp/peel with
      additional species of ACN 54 from the seeds (5-24%). Subspecies (ssp.) sinensis
      differed from ssp. mongolica and rhamnoides by having a higher proportion of TAG
      of ACN 52 (27% vs. 21% and 22%, P< 0.05) and a lower proportion of ACN 54 (71%
      vs. 79% and 78%, P < 0.01) in seed TAG. Seed TAG of ssp. mongolica contained a
      higher proportion of more unsaturated species compared with those of the two
      other subspecies. Berry TAG of ssp. mongolica had the highest proportion of
      molecular species of ACN 48 due to the higher proportion of palmitic and
      palmitoleic acids and the lower seed content of the berries. Overall, palmitic
      acid favored the sn-1 and sn-3 positions. The order of preference of unsaturated
      FA for the sn-2 position depended at least partially on the FA combination of
      TAG. Seed TAG of ssp. mongolica contained a higher proportion of alpha-linolenic
      acid in the sn-2 position than those of ssp. sinensis. In berry TAG, ssp.
      mongolica had the highest proportions of palmitoleic and linoleic acids in the sn
      2 position, and the lowest proportion of oleic/cis-vaccenic acid in the sn-2
      position, among the three subspecies.

PMID- 16808151
TI  - Differential effect of lysophospholipids on activities of human plasma
      paraoxonase1, either soluble or lipid-bound.
AB  - Interaction of paraoxonase1 (PON1) with lysophospholipids was examined with
      respect to activity regulation and binding property. Paraoxonase activity of
      purified PON1 was partially inhibited by palmitoyl-lysophosphatidyl-glycerol
      (palmitoyl-lysoPG) and lysophosphatidylinositol (lysoPI), which had a stimulatory
      effect on arylesterase and diazoxonase activities. The selective inhibition of
      paraoxonase activity by palmitoyl-lysoPG, characterized by noncompetitiveness and
      charge interaction, was also observed with HDL- or dimyristoylphosphatidylcholine
      (DMPC)-bound PON1. Meanwhile, lysophosphatidylcholine (lysoPC) stimulated all
      three activities of purified PON1, although it stimulated DMPC-bound or HDL-bound
      PON1 to a lesser extent. The stimulatory action of lysophospholipids was observed
      around their CMC, suggesting that micelle formation of lysophospholpids might be
      involved in the stimulation of PON1 activity. Presumably in support of this, the
      tryptophan fluorescence intensity of PON1 was increased by lysophospholipids at
      concentrations required for the stimulation of PON1 activity. Separately, lysoPC
      stimulation was less remarkable for DMPC-bound PON1 than for either
      dimyristoylphosphatidylserine (DMPS)- or dimyristoylphosphatidylglycerol-bound
      PON1, suggesting a tight association between PON1 and DMPC. In support of this,
      the stimulatory role of apolipoprotein A-I was less prominent for DMPC-bound PON1
      than for DMPS-bound PON1. Taken together, these data suggest that the inhibition
      of paraoxonase activity by lysoPG or lysoPI may be due to binding to a site
      distinct from the active center, whereas the stimulation by lysophospholipid may
      be ascribed to the micelle formation around the lipid-associable region of PON1.

PMID- 16808153
TI  - NMR characterization of dihydrosterculic acid and its methyl ester.
AB  - Cyclopropane FA occur in nature in the phosphoplipids of bacterial membranes, in
      oils containing cyclopropene FA, and in Litchi sinensis oil. Dihydrosterculic
      acid (2-octyl cyclopropaneoctanoic acid) and its methyl ester were selected for
      1H and 13C NMR analysis as compounds representative of cyclopropane FA. The 500
      MHz 1H NMR spectra acquired with CDCl3 as solvent show two individual peaks at 
      0.30 and 0.60 ppm for the methylene protons of the cyclopropane ring. Assignments
      were made with the aid of 2D correlations. In accordance with previous
      literature, the upfield signal is assigned to the cis proton and the downfield
      signal to the trans proton. This signal of the trans proton is resolved from the
      peak of the two methine protons of the cyclopropane ring, which is located at
      0.68 ppm. The four protons attached to the two methylene carbons alpha to the
      cyclopropane ring also show a split signal. Two of these protons, one from each
      methylene moiety, display a distinct shift at 1.17 ppm, and the signal of the
      other two protons is observed at 1.40 ppm, within the broad methylene peak. The
      characteristic peaks in the 13C spectra are also assigned.

PMID- 16808154
TI  - Effect of temperature on the fatty acid composition and temporal trajectories of
      fatty acids in fasting Daphnia pulex (Crustacea, Cladocera).
AB  - Poikilothermic organisms accumulate highly unsaturated FA (HUFA) in their lipids
      at reduced temperatures to maintain cell membrane fluidity. In this study we
      investigated the effect of temperature on temporal trajectories of FA of fasting
      Daphnia pulex cultured on a HUFA-free diet. Daphnia pulex populations were
      maintained for 1 mon at 22 and 11 degrees C and were fed the chlorophyte
      Ankistrodesmus falcatus. We observed conversion of C18 FA precursors to EPA
      (20:5n3) and arachidonic acid (ARA; 20:4n6) in D. pulex. We showed that long-term
      exposure to cold temperature causes a significant increase in EPA. HUFA such as
      ARA and EPA are highly conserved during starvation. Therefore, D. pulex has the
      biosynthetic capacity to adjust and to maintain the content of HUFA required to
      survive at low temperatures.

PMID- 16808155
TI  - Effects of storage time and added antioxidant on fatty acid composition of red
      blood cells at -20 degrees C.
AB  - The stability of PUFA in venous red blood cells (RBC) of women aged 25 to 55
      years (n = 12) was investigated during storage at -20 degrees C. The RBC sample
      from each participant was divided into seven portions: one baseline with the
      antioxidant BHT, another without BHT, samples without BHT stored for 2, 4, 9, or
      17 wk, and samples with BHT stored for 17 wk. No difference was found in
      proportions of PUFA at baseline and after storage for 2 and 4 wk without BHT, and
      17 wk with BHT. After 9 wk without BHT the proportion of 22:6n-3 in RBC was
      lower, and after 17 wk without BHT proportions of all PUFA were lower than at
      baseline. High proportion of 22:6n-3 in RBC at baseline was associated with more
      stable concentration of total FA in RBC without BHT during 17 wk. The findings
      indicate that PUFA in RBC from healthy women are stable at -20 degrees C for 4 wk
      without BHT and for at least 17 wk with BHT.

PMID- 16808156
TI  - Effect of antiretroviral agents on triglyceride levels in HIV-1-infected pregnant
      women.

PMID- 16808157
TI  - Differentiation of human amniotic membrane cells into osteoblasts in vitro.
AB  - OBJECTIVE: Pluripotent stem cells may be exist in the human amniotic membrane
      (HAM). The present article was aimed at establishing HAM cell lines and
      investigating their differentiation into osteoblasts in vitro. METHODS: HAM cell
      lineswere established using routine cell culture techniques and expanded in
      vitro. RESULTS: HAM cells were propagated from 45 out of 50 specimens (90%) and
      all were maintained normal karyotypes in vitro. Alkaline phosphatase (ALP)
      activity and alizarin red S stain were positive for 12 out of 22 HAM cell lines
      (54.5%). The 22 HAM cell lines were selectedat random. CONCLUSIONS: This study
      demonstrates that this isolation method II was more effective for establishing
      cell lines which differentiate into osteoblast rather than method I.

PMID- 16808158
TI  - [New treatments of choroidal neovascularization].

PMID- 16808159
TI  - [Effect of photodynamic therapy with ATX-S 10 (Na) on experimental choroidal
      neovascularization].
AB  - PURPOSE: To evaluate an appropriate irradiative condition for selective occlusion
      of experimental choroidal neovascularization(CNV) with photodynamic therapy (PDT)
      using ATX-S 10 (Na). METHODS: Experimental CNV was induced in monkey eyes by
      laser photocoagulation. PDT(dose of irradiative energy 40 to 80J/cm2) was
      performed after 3.5 mg/kg of body weight intravenous injections of ATX-S 10(Na).
      CNV and retinal vessel occlusion induced by PDT was evaluated by fluorescein
      angiography (FA) at 1 and 7 days after irradiation. If FA showed no fluorescein
      dye leakage from CNV at 1 and 7 days after irradiation, CNV was evaluated by
      histopathological analysis at 7 days after irradiation. RESULTS: Within 30 to 33
      minutes after ATX-S 10(Na) injection and irradiation with 50 to 60 J/ cm2, FA
      showed no fluorescein dye leakage from CNV and no closure of retinal vessels at 1
      and 7 days after irradiation. Light micrographs showed occluded CNV, and retinal
      vessels remained patent and there was no apparent change in the inner layer of
      the retina. CONCLUSIONS: Irradiative condition of ATX-S10 (Na) 3.5 mg/kg was
      appropriate 30 to 33 minutes after ATX-S 10(Na) injection and irradiation with 50
      to 60 J/cm2.

PMID- 16808160
TI  - [Evaluation of cases of polypoidal choroidal vasculopathy showing classic
      choroidal neovascularization in their natural course].
AB  - BACKGROUND: Some cases of polypoidal choroidal vasculopathy (PCV) in their
      natural course develop into classic choroidal neovascularization(CNV) as shown by
      fluorescein angiography (FA) findings. SUBJECTS AND METHOD: We evaluated 8 eyes
      of 8 PCV patients showing classic CNV by FA findings, using indocyanine green
      angiography (IA) and optical coherence tomography(OCT). RESULT: All patients
      showed subretinal grayish exudates, which were considered fibrinous. Five cases
      were recognized as true subretinal CNV according to IA and OCT findings. The
      other 3 patients showed polypoidal dilatation with vascular networks by IA, and a
      moderately reflective mass considered fibrinous over the polypoidal elevation of
      retinal pigment epithelium (RPE) by OCT. CONCLUSION: Both true CNV and PCV with
      fibrin are present in PCV patients showing classic CNV. It requires care to
      determine proper treatment.

PMID- 16808161
TI  - [Optic nerve atrophy after vitrectomy for diabetic retinopathy: its systemic and
      local risk factors].
AB  - PURPOSE: To evaluate the incidence and risk factors of optic nerve atrophy after
      vitrectomy for diabetic retinopathy. SUBJECTS AND METHODS: Clinical charts of 48
      eyes of 40 patients who underwent vitrectomy for diabetic retinopathy were
      retrospectively reviewed. The relationship between postoperative optic nerve
      atrophy and patients' physical condition was statistically analyzed. RESULT:
      Postoperative optic nerve atrophy, distinct from glaucomatous optic nerve
      atrophy, occurred in 5 eyes (10.4%). Its incidence was correlated with higher
      plasma creatinine concentration (p=0.001), proliferative diabetic retinopathy (p=
      0.046), and retinal white vessel formation (p= 0.007). Maintenance of the best
      postoperative visual acuity was difficult in the patients with optic nerve
      atrophy. CONCLUSION: Patients with proliferative diabetic retinopathy accompanied
      by renal dysfunction were at high risk of optic nerve atrophy after vitrectomy.

PMID- 16808162
TI  - [Clinical evaluation of primary position downbeat nystagmus].
AB  - PURPOSE: Primary position downbeat nystagmus is a vertical nystagmus with a rapid
      phase downwards presenting in any gaze. We evaluated causative lesions, etiology,
      and incidence by age groups. MATERIALS AND METHODS: Twenty-five patients with
      primary position downbeat nystagmus were enrolled in this study. Their causative
      lesions, etiology, and frequency by age group were investigated. We divided the
      patients into 3 groups depending on age; under 30, from 30 to 60, and over 60
      years. RESULT: Cerebrovascular disorder was diagnosed in 5 patients. Four
      patients had cerebellar degeneration. Three patients had multiple sclerosis or
      Arnold-Chiari malformation. Two patients had cerebellar tumor. In the young group
      under 30, etiology was mainly cerebellar tumor or multiple sclerosis. Especially
      cerebellar tumor was limited to this group. In the middle age group, there was no
      distinctive tendency. In the older group over 60 years, cerebrovascular disorder
      was predominant. In 10 patients with intracranial lesions, the foci were located
      in the cerebellum, pons, or medulla oblongata. CONCLUSION: The causes of primary
      position down beat nystagmus tended to be age-dependent. The locations of
      causative lesions were the cerebellum and the inferior brain stem.

PMID- 16808163
TI  - [A case of Prader-Willi syndrome treated by vitrectomy].
AB  - BACKGROUND: We report a successful treatment by vitrectomy in an adult case of
      Prader-Willi syndrome. CASE REPORT: We encountered a case of Prader-Willi
      syndrome in a 29-year-old male patient with proliferative diabetic retinopathy
      and cataract. We performed a vitrectomy and a cataract extraction on the patient.
      Initial examination showed proliferative diabetic retinopathy in both eyes.
      Funduscopy revealed tractional retinal detachment with atrophic retina in the
      right eye and retinal detachment in the inferior half of the fundus with vitreous
      hemorrhage in the left eye. We performed a vitrectomy with a combination of
      phacoemulsification and intraocular lens implantation only on the left eye.
      Visual acuity in the left eye increased from counting fingers preoperatively to
      0.6(n.c) postoperatively. The right eye was left untreated because the visual
      prognosis was not expected to improve even if the eye received surgical
      intervention. The final visual acuity in the right eye was no light perception at
      the end of the follow-up period. CONCLUSION: Careful follow-up and early
      treatment are necessary for patients with diabetic retinopathy accompanied by
      Prader-Willi syndrome as it could develop into blindness.

PMID- 16808164
TI  - [A case of normal-tension glaucoma with impaired eye movements in a young
      patient].
AB  - BACKGROUND: We report a case of normal-tension glaucoma(NTG) with impaired eye
      movements in a young patient. CASE: A 22-year-old man with enlarged optic disc
      cuppings and visual field defects was suspected to have NTG, and was found, upon
      examination, to have impaired eye movements. Intraocular pressure recordings,
      including diurnal variation, were under 21 mmHg. Gonioscopic findings were
      normal. Magnetic resonance image(MRI) showed no particular findings. The patient
      was diagnosed with NTG. Using the 123I-iodoamphetamine single photon emission
      computed tomography (123I-IMP SPECT), decreased cerebral blood flow was detected
      in the patient's occipital lobe and an electro-oculogram showed impaired eye
      movements during smooth pursuit. The patient's visual field defects have
      increased over the last two years, but, no accompanying change in his eye
      movements has been observed. CONCLUSION: The patient in this case has NTG with
      impaired eye movements and decreased cerebral blood flow suggesting that some
      disorder of the central nervous system may be one of the causative mechanisms of
      NTG.

PMID- 16808165
TI  - [Starlike branched and hyperbranched biodegradable polymer systems as DNA
      carriers].
AB  - The information on the synthesis of new biologically compatible and biologically
      degradable DNA carriers based on starlike polymer conjugates of proteins (lysine
      dendrimers and their derivatives) and hyperbranched polyamino acids is reviewed.
      Their capacity to bind and compact DNA and to provide for transfection is
      discussed based on results obtained with model systems. The English version of
      the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see
      also http://www.maik.ru.

PMID- 16808166
TI  - [The formation and role of beta-amyloid peptides in neurons upon amyloidosis].
AB  - The formation mechanism of amyloid peptides in normally functioning neuron and
      upon the development of amyloidosis resulting in neuron death is described.
      Amyloid peptides are formed by enzymatic processing of a large protein precursor
      and participate in intermolecular interactions after conformational
      rearrangements resulting in the formation of pathogenic structures. They enter
      into the cascade of molecular and cellular events leading to amyloidosis and
      death of nervous cells. These molecular events clarify the relation between the
      conformation and function of neuropathogenic peptides and the role of this
      relation in the development of pathology of differentiated neurons. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no.
      3; see also http://www.maik.ru.

PMID- 16808167
TI  - [Development and application of an expert system for analysis of the functional
      continuum of regulatory peptides].
AB  - An expert computer system was developed to analyze the effects of regulatory
      peptides (RPs) and some other biologically active compounds. The database
      includes information on their structures and physiological and inductive effects
      taking in account the method of administration, doses, and types of organisms.
      The developed method of vector representation of RP effects and the software
      modules provide for the estimation of the role of single RPs and their
      combinations in the regulatory system of organism. The expert system was used for
      solving the following tasks: (1) an analysis of the structural and functional
      organization of the RP continuum and a search for effective RP combinations
      regulating the levels of anxiety, depression, cognitive processes, etc; (2)
      design of a network of complicated cross inductive connections of major members
      of RP families; and (3) an analysis of the peculiar features of functioning of
      numerous internal reward factors. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also
      http://www.maik.ru.

PMID- 16808168
TI  - [Arachidonoyl amino acids and arachidonoyl peptides: synthesis and properties].
AB  - N-Arachidonoyl (AA) derivatives of amino acids (glycine, phenylalanine, proline,
      valine, gamma-amino butyric acid (GABA), dihydroxyphenylalanine, tyrosine,
      tryptophan, and alanine) and peptides (Semax, MEHFPGP, and PGP) were synthesized
      in order to study the biological properties of acylamino acids. The mass spectra
      of all the compounds at atmospheric pressure electrospray ionization display the
      most intense peaks of protonated molecular ions; the detection limits for these
      compounds are 10 fmol per sample. AA-Gly showed the highest inhibitory activity
      toward fatty acid amide hydrolase from rat brain (IC50 6.5 microM) among all the
      acylamino acids studied. AA-Phe, AA-Tyr, and AA-GABA exhibited a weak but
      detectable inhibitory effect (IC50 55, 60, and 50 microM, respectively). The
      acylated amino acids themselves, except for AA-Gly, were stable to the hydrolysis
      by this enzyme. All the arachidonoylamino acids inhibited cabbage phospholipase D
      to various degrees; AA-GABA and AA-Phe proved to be the most active (IC50 20 and
      27 microM, respectively). Attempts to detect the biosynthesis of AA-Tyr in
      homogenates of rat liver and nerve tissue showed no formation in vitro of either
      this acylamino acid or AA-dopamine and AA-Phe, the products of its metabolism.
      The highest contents of these metabolites were detected in liver homogenate and
      in the brain homogenate, respectively. Acylamino acids exert no cytotoxic effect
      toward the glioma C6 cells. It was shown that N-acylation of Semax with
      arachidonic acid results in enhancement of its hydrolytic stability and increases
      its affinity for the sites of specific binding in rat cerebellum membranes. The
      English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol.
      32, no. 3; see also http://www.maik.ru.

PMID- 16808169
TI  - [Conformational analysis of cysteine-containing peptides and prospects of their
      application to 213Bi chelating in antitumor therapy].
AB  - The method of conformational analysis was applied to the spatial structures of
      peptide analogues of phytochelatins and some fragments of metallothioneins: (Cys
      Gly)3, (Cys-Gly)3Asp, (Cys-Gly)3Glu, (Cys-betaAla)3, (Cys-gammaGlu)3, and (Cys
      Gly-Gly)3. All the possible low-energy conformations of the molecules were
      revealed and the role of intra- and inter-residual interactions in the formation
      of their spatial structures was determined. A different tendency of the molecules
      under study for acceptance of conformations favorable for binding bismuth ions
      was shown. Low-energy structures providing an optimum binding of bismuth ion were
      shown to be most frequent for (Cys-betaAla)3 peptide. Among the analogues of
      peptide fragments of the metallothioneins, lacking in natural peptides, low
      energy pentapeptide CCXXC fragments (where X = Gln, Asn, Phe, Tyr, and Gly) were
      revealed. In the alpha-helical conformations of these pentapeptides, the distance
      between the sulfur atoms corresponds to that in Bi2S3. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also
      http://www.maik.ru.

PMID- 16808170
TI  - [Effect of a cholecystokinin tetrapeptide analogue on opioid reception under
      acute and chronic morphine administration].
AB  - Effects of a modified CCK-4, a tetrapeptide fragment of cholecystokinin, on
      opioid reception and cAMP level were studied. The modified CCK-4 changed the
      ligand binding of the opioid receptors of mu- and sigma-types in vitro. In vivo,
      it prevented changes in opioid reception caused by a single morphine injection or
      by morphine withdrawal after its long-term introduction. The CCK-4 analogue did
      not exert any effect in the state of intoxication after a long-term introduction
      of morphine or even promoted the morphine effect. The introduction of the CCK-4
      analogue alone or together with morphine changed the forskoline-stimulated level
      of cAMP. These changes depended on the brain structure and the duration of the
      introduction of morphine and the CCK-4 analogue. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also
      http://www.maik.ru.

PMID- 16808171
TI  - [The modulating effect of amino acids on an organotypic culture of lymphoid
      tissue].
AB  - The effect of 20 essential and nonessential L-amino acids on the dynamics of
      development of spleen explants from 1- and 21-day-old rats on an organotypic
      tissue culture was studied. The hydrophilic amino acids with a higher molecular
      mass (asparagine, lysine, arginine, and glutamic acid) induced an inhibitory
      effect on the growth zone of explants of immature tissue from 1-day-old animals
      and an opposite, stimulating effect on the mature spleen tissue of 21-day-old
      rats. An immunohistochemical analysis revealed a reciprocal correlation between
      the expression of the proapoptotic protein p53 and the cell proliferation upon
      the action of lysine, asparagine, and glutamic acid. The role of polar amino
      acids in the modulation of cell proliferation and apoptosis in dependence on the
      period of ontogenesis was determined. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also
      http://www.maik.ru.

PMID- 16808172
TI  - [Biological activity and pharmacological prospects of lupane terpenoids: II.
      Semisynthetic lupane derivatives].
AB  - The discussion of lupane triterpenoids as prospective medicinal preparations is
      continued, and semisynthetic triterpenoids are being discussed. Acyl derivatives
      that mainly exhibit high anti-HIV, antitumor, and organo-protective activities
      are described. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

PMID- 16808173
TI  - [The synthesis of arginine derivatives of chromone and azauracil].
AB  - The coupling of N-succinimide esters of 3-[7-hydroxy-3-(4-methyl-1,3-thiazol-2
      yl)-6-ethyl-4-oxo-4H-chromen-2-yl]propanoic acid and 5-carboxymethyl-6-azauracil
      with free arginine yielded the corresponding arginine derivatives, which were
      purified by crystallization. The structures of the compounds were confirmed by 1H
      NMR spectroscopy. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

PMID- 16808174
TI  - [Molecular environment of the subdomain IIIe loop of the RNA IRES element of
      hepatitis C virus on the human 40S ribosomal subunit].
AB  - The molecular environment of the internal ribosome entry site (IRES) element of
      hepatitis C viral (HCV) RNA in the binary complex with the human 40S ribosomal
      subunit was studied. To this end, RNA derivatives bearing mild UV-reactive
      perfluorophenylazide groups at nucleotide G87 in IRES domain II and at nucleotide
      A296 in the subdomain IIIe loop were used, which were prepared by the RNA
      complementarily-addressed modification with alkylating oligonucleotide
      derivatives. None of the RNA derivatives were shown to be crosslinked to the 18S
      rRNA of the 40S subunit. It was found that the photoreactive group of IRES
      nucleotide A296 was crosslinked to the 40S subunit S2/S3a, S5, and p40 (SOA)
      proteins. No protein crosslinking was observed for the RNA derivative containing
      the same photoreactive group in nucleotide G87. It was concluded that the
      subdomain IIIe loop of the HCV RNA IRES element in the complex with the 40S
      subunit is located on the outer subunit surface between the head and the body
      next to the "beak" near the entrance into the mRNA-binding channel. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no.
      3; see also http://www.maik.ru.

PMID- 16808175
TI  - [New ceramides from sea sponge Oceanapia sp].
AB  - Total ceramides containing nonbranched and iso-branched C18- and C19
      phytosphingosines acylated with non-hydroxylated fatty acids were isolated from a
      marine sponge Oceanapia sp. The structures of these compounds were determined by
      HPLC, NMR, MALDI-TOF MS, and GLC-MS of the Me3Si derivatives and by chemical
      transformations. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

PMID- 16808176
TI  - [Cytotoxic compounds from the marine actinobacterium].
AB  - We isolated a bioactive streptomycete from marine sediment samples collected at
      Bay of Bengal, India, during our systematic study of marine actinobacteria. The
      taxonomic studies indicated that the isolate is related to Strepomyces
      corchorusii. However, it differed in certain aspects, and, hence, was designated
      as S. corchorusii AUBN(1)/7. A solvent extraction followed by a chromatographic
      purification helped obtain from the isolate two cytotoxic compounds, which were
      identified as resistomycin, a quinone-related antibiotic, and tetracenomycin D,
      an anthraquinone antibiotic, on the basis of spectral data of pure compounds.
      They demonstrated in vitro a potent cytotoxic activity against cell lines HMO2
      (gastric adenocarcinoma) and HepG2 (hepatic carcinoma) and also exhibited weak
      antibacterial activities against Gram-positive and Gram-negative bacteria. The
      English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol.
      32, no. 3; see also http://www.maik.ru.

PMID- 16808178
TI  - Rise of the dental phoenix.

PMID- 16808177
TI  - [Binding of phosphatidylinositol-3,4,5-triphosphate to 45-kDa sec14-like protein
      from the rat olfactory epithelium in liposomes].
AB  - The binding of phosphatidylinositol-3,4,5-triphosphate to a protein with
      molecular mass of 45 kDa from rat olfactory epithelium (p45) was investigated
      using a model membrane system. Liposomes containing a mixture of phospholipids
      (phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol-3,4,5
      triphosphate) were used in the study. The binding of the protein to liposomes
      caused by its interaction with phosphatidylinositol-3,4,5-triphosphate was
      confirmed by cosedimentation and immunoblotting with chemiluminescent detection
      using monoclonal antibodies to the native protein p45. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also
      http://www.maik.ru.

PMID- 16808179
TI  - The National Human Resources plan for health in South Africa 2006.

PMID- 16808180
TI  - A critical evaluation of the committee of preliminary inquiry of the Health
      Professions Council of South Africa, with specific reference to maxillo-facial
      and oral surgery (Part 1).

PMID- 16808182
TI  - Treatment of aesthetic problems in paediatric dentistry.
AB  - Aesthetic problems in childhood and adolescence can have a significant effect on
      psychosocial development and interaction with peers. Abnormalities of shape,
      size, colour and structure of the whole or part of the anterior dentition of
      children can lead to such problems. This article outlines the most appropriate
      options for the clinical management of different aetiological categories of
      aesthetic problems, and develops a hierarchy of intervention that should be
      pursued in a logical order until a satisfactory cosmetic outcome is achieved.
      These techniques are readily available to most dental practitioners and there is
      no reason for a child to have to wait until late adolescence for treatment. Dent
      Update 2003; 30: 307-313 CLINICAL RELEVANCE: Aesthetic problems in children and
      adolescents may be treated by a variety of techniques.

PMID- 16808181
TI  - Post-operative sequelae of lower third molar removal: a literature review and
      pilot study on the effect of Covomycin D.
AB  - Pain, swelling and dry socket formation commonly follow third molar surgery. The
      objective was to investigate the effect of intrasocket Covomycin D, an
      antibiotic/anti-inflammatory medication, on pain, swelling and dry socket
      following lower third molar removal. Nineteen subjects had bilateral lower third
      molars removed. The patients were blinded to the side of medication; the opposite
      side acted as the control; post-operatively a pain visual analogue scale was
      completed, the side of the worst swelling and the incidence of dry socket noted.
      The data was analysed using the Wilcoxons matched pairs signed ranks test.
      Results showed that the pain score was lower for the medicated side in 11
      patients on day one and in 16 patients over the six day post-operative period (p
      < 0.6). The swelling was less on the medicated side in fourteen patients. Three
      dry sockets developed in non-medicated sockets. In conclusion this study shows
      that the use of intra-socket Covomycin D favourably influences post-operative
      sequelae following lower third molar removal.

PMID- 16808183
TI  - Updates on local anaesthetics.
AB  - This article draws from a book entitled: "A practical approach to hazards of
      local anaesthetic injections" by DP Barnard.

PMID- 16808184
TI  - Implants and age.

PMID- 16808185
TI  - General practitioner's pathology. Case 4. Internal (or pulpal) resorption of
      dentine.

PMID- 16808186
TI  - Sedation corner 9. Antidepressants.

PMID- 16808187
TI  - General practitioner's radiology. Case 41. Central giant cell granuloma .

PMID- 16808188
TI  - How to help smokers quit: Part 2.

PMID- 16808189
TI  - MOM project--Mission of Mercy.

PMID- 16808190
TI  - Dental anxiety and substance abuse relapse.

PMID- 16808191
TI  - Iraq eye.

PMID- 16808192
TI  - Flossing.

PMID- 16808193
TI  - Ease your workload by automating patient communication.

PMID- 16808194
TI  - Dental implants: exceptional not experimental.

PMID- 16808195
TI  - You gotta know when to hold 'em...
AB  - Putting together a winning team is certainly not a game. It requires skill,
      diligence, and a little bit of luck. The poker analogy is simply a tool to
      present critical information in a fun, relevant format. However, with a
      proactive, pragmatic, and creative approach to hiring, you will improve your odds
      of successfully hiring the perfect match for your practice. Good luck!

PMID- 16808196
TI  - The treatment of hepatic metastases in colorectal carcinoma.
AB  - Colorectal carcinoma is the third most common cause of cancer death in the United
      States, with 135,000 new cases and 55,000 deaths annually. Ultimately, two-thirds
      (99,000) of all patients with colorectal cancer will develop metastasis to the
      liver and other organs in their life span, making metastatic colorectal cancer
      the second leading cause of cancer-related death in North America. The optimal
      management of these patients has become increasingly complex with the myriad of
      treatment options that are available. Because the timing of any therapy (surgery,
      chemotherapy, or others) has become integral to the success of the treatment, a
      collaborative approach involving multiple specialties is needed for the best
      patient outcome. Defined clinical and pathologic determinants of outcome have
      been demonstrated to effect the overall and disease-free survival of patients
      with metastatic colorectal cancer. Understanding of these determinants remains
      essential to any treating physician and has lead to significant paradigm shifts
      in the management of patients with metastatic colorectal cancer.

PMID- 16808197
TI  - Advantages of laparoscopic appendectomy in the elderly.
AB  - Laparoscopic appendectomy (LA) has gained in popularity in recent years. The
      number of elderly patients undergoing appendectomy has increased as that segment
      of the population has increased in number; however, the utility and benefits of
      LA in the elderly population are not well established. We hypothesized that LA in
      the elderly has distinctive advantages in perioperative outcomes over open
      appendectomy (OA). We queried the 1997 to 2003 North Carolina Hospital
      Association Patient Data System for all patients with the primary ICD-9 procedure
      code for OA and LA. Patients > or = 65 years of age (elderly) were identified and
      reviewed. Outcomes including length of stay (LOS), charges, complications,
      discharge location, and mortality were compared between the groups. There were
      29,244 appendectomies performed in adult patients (>18 years old) with 2,722 of
      these in the elderly. The annual percentage of LA performed in the elderly
      increased from 1997 to 2003 (11.9-26.9%, P < 0.0001). When compared with OA,
      elderly patients undergoing LA had a shorter LOS (4.6 vs 7.3 days, P = 0.0001), a
      higher rate of discharge to home (91.4 vs 78.9%, P = 0.0001) as opposed to a step
      down facility, fewer complications (13.0 vs 22.4%, P = 0.0001), and a lower
      mortality rate (0.4 vs 2.1%, P = 0.007). When LA was compared with OA in elderly
      patients with perforated appendicitis, LA resulted in a shorter LOS (6.8 vs 9.0
      days, P = 0.0001), a higher rate of discharge to home (86.6 vs 70.9%, P =
      0.0001), but equivalent total charges (dollars 22,334 vs dollars 23,855, P =
      0.93) and mortality (1.0 vs 2.98%, P = 0.10). When elderly patients that
      underwent LA were compared with adult patients (18-64 years old), they had higher
      total charges (dollars 16,670 vs dollars 11,160, P = 0.0001) but equivalent
      mortality (0.37 vs 0.15%, P = 0.20). The use of laparoscopy in the elderly has
      significantly increased in recent years. In general, the safety and efficacy of
      LA is demonstrated by a reduction in mortality, complications, and LOS when
      compared with OA. The laparoscopic approach to the perforated appendix in the
      elderly patient has advantages over OA in terms of decreased LOS and a higher
      rate of discharge to home as opposed to rehabilitation centers, nursing homes, or
      skilled nursing care. When compared with all younger adults, the laparoscopic
      approach in the elderly was associated with equal mortality rates even though
      hospitalization charges were higher. Laparoscopy may be the preferred approach in
      elderly patients who require appendectomy.

PMID- 16808198
TI  - Pediatric pelvic fractures: a marker for injury severity.
AB  - Pelvic fractures comprise a small number of annual Level I pediatric trauma
      center admissions. This is a review of the University of Chicago Level I
      Pediatric Trauma Center experience with pediatric pelvic fractures. This is a
      retrospective review of the University of Chicago Level I Pediatric Trauma Center
      experience with pediatric pelvic fractures during the 12-year period from 1992 to
      2004. From 1992 to 2004, there were 2850 pediatric trauma admissions. Thirteen
      patients were identified with pelvic fractures; seven were boys and six were
      girls. The average age was 8 years old. The mechanism of injury in all cases was
      motor vehicle related; 11 patients (87%) sustained pedestrian-motor vehicle
      crashes. According to the Torode and Zeig classification system, type III
      fractures occurred in eight patients (62%) and type IV fractures occurred in six
      patients (31%). Associated injuries occurred in eight patients (62%). Seven of
      these patients (88%) had associated injuries involving two or more organ systems.
      Of the associated injuries, additional orthopedic injuries were the most common,
      occurring in 62 per cent of our patients. Neurological injuries occurred in 54
      per cent of patients, vascular injuries in 39 per cent, pulmonary injuries in 31
      per cent, and genitourinary injuries in 15 per cent. Five patients (38%) were
      treated operatively; only two patients underwent operative management directly
      related to their pelvic fracture. The remaining three patients underwent
      operative management of associated injuries. The mortality rate was 0 per cent.
      Although pelvic fractures are an uncommon injury in pediatric trauma patients,
      the morbidity associated with these injuries can be profound. The majority of
      pelvic fractures in children are treated nonoperatively, however, more than one
      half of these patients have concomitant injuries requiring operative management.
      When evaluating and treating pediatric pelvic fractures, a systematic
      multidisciplinary approach must be taken to evaluate and prioritize the pelvic
      fracture and the associated injuries.

PMID- 16808199
TI  - Attracting medical students to surgical residency programs.
AB  - With the goals of creating a better match between medical students and general
      surgery programs and providing a program that is desirable to medical students
      who are interested in pursuing careers in surgery, a survey was designed to
      categorize student interests and to determine what factors are used in choosing a
      general surgery program. The survey focused on the reasons that surgical resident
      candidates select a program. Each statement was rated for importance on a 5-point
      scale, and then the top 10 statements were ranked in order of importance. The
      survey was distributed to 19 community hospitals, 23 university programs, and
      medical students interviewing for surgical residency. A total of 286 surveys were
      returned from 18 programs and medical students. The statements with the three
      highest ratings were "amount of operative exposure," "diversity of operative
      cases," and "perceived relationships among faculty and residents." "Amount of
      operative exposure," "diversity of operative cases," and "ability to pursue
      fellowship training after residency" received the top rankings. There was a
      significant difference between men and women in the ratings of three statements.
      However, there was no difference with the ranking of the statements. There was
      also a significant difference between residents early and late in their training
      on ratings of five statements and on the ranking of two statements. The ratings
      of six statements were significantly different between community and university
      programs. A significant difference between types of program was also found with
      the rankings of four statements. There was a difference between small and large
      programs on two ratings of statements and one ranking. This data provides a
      useful resource for programs and candidates in preparing for candidate/residency
      selection.

PMID- 16808201
TI  - Care of critically ill surgical patients using the 80-hour Accreditation Council
      of Graduate Medical Education work-week guidelines: a survey of current
      strategies.
AB  - As a result of the recently mandated work-hour restrictions, it has become more
      difficult to provide 24-hour intensive care unit (ICU) in-house coverage by the
      general surgical residents. To assess the current state of providing appropriate
      continuous care to surgical critical care patients during the era of resident
      work-hour constraints, a national survey was conducted by the Association of
      Program Directors of Surgery. The results revealed that 37 per cent of programs
      surveyed have residents other than general surgery housestaff providing cross
      coverage and writing orders for surgical ICU patients. Residents in emergency
      medicine, anesthesia, family medicine, otorhinolaryngology,
      obstetrics/gynecology, internal medicine, urology, and orthopedic surgery have
      provided this cross-coverage. Some found it necessary to use physician extenders
      (i.e., nurse practitioners or physician assistants), thereby decreasing the
      burden of surgical housestaff coverage. The results indicated that 30 per cent
      use physician extenders to help cover the ICU during daytime hours and 11 per
      cent used them during nighttime hours. In addition, 24 per cent used a "night
      float" system in an attempt to maintain continuous care, yet still adhere to the
      mandated guidelines. In conclusion, our survey found multiple strategies,
      including the use of physician extenders, a "night-float" system, and the use of
      nongeneral surgical residents in an attempt to provide continuous coverage for
      surgical ICU patients. The overall outcome of these new strategies still needs to
      be assessed before any beneficial results can be demonstrated.

PMID- 16808200
TI  - Accelerated migration and proliferation of smooth muscle cells cultured from
      neointima induced by a vena cava filter.
AB  - Formation of a neointima is associated with grafted artery or vein, angioplasty,
      and stent and inferior vena cava filter (IVCF) implantation. Contributing to the
      neointima is a population of vascular smooth muscle cells (SMC) that migrates
      from media and subsequently proliferates within intima. The purpose of this
      present study was to culture SMC from normal vessel wall and from neointima and
      to compare migration and growth of these cells. Neointima was stimulated in the
      vena cava of pigs by placement of an IVCF for 30 days. Tissue was taken from the
      thickened wall between the struts and from a normal segment of the IVCF. After
      removal of the endothelium and adventitia, explants were placed in culture dishes
      and were observed for the migration of cells. Immunoassay for smooth muscle alpha
      actin was used to identify cell origin. Proliferation was determined by cell
      counting. The cell cycle regulator cyclin D1 was detected by Western blot
      analysis. SMC phenotype was confirmed by positive immunostaining for smooth
      muscle alpha-actin. Cells migrated from the neointimal explants (NI-SMC) more
      rapidly than cells from explants of normal media (NM-SMC). Proliferation of NI
      SMC was also more rapid than NM-SMC with or without exogenous mitogens. NI-SMC
      expressed more cyclin D1 than NM-SMC. Injury to the vena cava triggered neointima
      formation characterized by the expansion of a population of SMC with increased
      migration and replication compared with SMC from normal regions of the vessel.

PMID- 16808202
TI  - Hemodynamic monitoring of organ donors: a novel use of the esophageal echo
      Doppler probe.
AB  - The esophageal Doppler monitoring (EDM) technology is well described in the
      literature. As it evolved over the last several years, the use of EDM has found
      expanded indications in various clinical settings. One of the areas where EDM has
      not been studied extensively is its use during optimization of organ donors
      before organ procurement. Close hemodynamic monitoring has become essential in
      the era of increasing use of extended organ donors. We present six cases of
      successful EDM use during preorgan procurement resuscitation of organ donors.
      Despite labile hemodynamics in the majority of these cases, EDM-guided
      optimization of resuscitative endpoints allowed successful organ procurements and
      transplants, including 12 kidneys, 6 livers, 3 hearts, 2 pancreases, and 2 lungs.
      The EDM technology is noninvasive, technically easy, and less expensive than the
      traditional pulmonary artery catheter. Other potential benefits of the EDM
      include its portability and possibility of deployment in any setting by trained
      organ procurement personnel or critical care nursing staff. In conclusion,
      successful organ procurement can be facilitated by the use of EDM technology in
      hemodynamically labile organ donor patients.

PMID- 16808203
TI  - A complication-free course ensures a survival advantage in patients after
      regional therapy for metastatic colorectal cancer.
AB  - Hepatic artery infusional (HAI) chemotherapy has been shown to favorably impact
      outcome in patients with metastatic colorectal cancer, but complications often
      preclude complete treatment. The purpose of this study was to determine whether
      HAI complications impact survival in these patients. Patients undergoing HAI pump
      placement at our institution from September 2001 to July 2004 were separated into
      terciles based on the number of treatments completed: < or = 1 (none), 2 to 4
      (partial), and > or = 5 (complete). Complications relating to pump placement or
      treatment were recorded for each and their impact on survival was determined.
      Kaplan-Meier survival in 15 patients receiving no treatment was significantly
      shorter than 7 patients completing therapy (P = 0.02). Thirty-three per cent of
      patients receiving no therapy were alive at 26 months, whereas 63 per cent of
      partially and 86 per cent of completely treated patients were alive at 32 and 30
      months, respectively. Patients receiving no treatment had more overall
      complications (80%) and significantly (P < 0.05) more pump-related complications
      (60%) than those completing therapy (43% and 0%, respectively). Cox regression
      revealed a significant correlation to gender (hazard ratio, 3.9), tumor size
      (hazard ratio, 1.17), and carcinoembryonic antigen level (hazard ratio, 1.02) to
      survival. Patients receiving complete HAI treatment survive longer than those
      receiving no treatment. Potentially preventable pump-related complications not
      only impacted the patients' ability to continue therapy, but survival times as
      well.

PMID- 16808204
TI  - Laparoscopic debridement of recurrent pancreatic abscesses in the hostile
      abdomen.
AB  - Recurrent necrotizing pancreatitis in the frozen or hostile abdomen remains a
      challenge. Percutaneous drainage is useful in these cases but often fails if
      there is significant pancreatic necrosis. We describe a technique for
      laparoscopic drainage of necrotic pancreas. The preexisting percutaneous drainage
      tract was sequentially dilated and a working thoracoscope was placed via a Hasson
      cannula. A pulsatile irrigation system was used to open the cavity for
      visualization and to wash away obvious necrotic debris. Working sequentially
      using the irrigation jet flow for debridement and visualization, we opened the
      entire tract and debrided a majority of the necrotic tissue. A large drainage
      tube was placed to allow the egress of any residual infection. Three patients to
      date have been treated with the above technique with no intraoperative
      complications. All three patients did well initially postoperatively and had
      adequate drainage. One patient developed a delayed pancreatic pseudocyst.
      Laparoscopic debridement via percutaneous drainage tract is a useful technique in
      the hostile abdomen.

PMID- 16808205
TI  - Predictors and outcomes of sternal wound complications in patients after coronary
      artery bypass graft surgery.
AB  - We sought to assess predictors and outcomes of sternal wound complications in
      patients after coronary artery bypass grafting (CABG). A nested, case-control
      study from a 10-year hospitalization cohort with prospective data collection was
      conducted. Included in the cohort were patients age 18 and above undergoing CABG
      surgery between March 1997 and July 2003 (n = 7889). Patients who underwent any
      surgery other CABG were excluded. Cases were matched to controls 1:3 on year of
      surgery. Cases were CABG patients with sternal wound complications, which was
      defined as requiring antibiotics and/or topical treatment, requiring extra
      nursing care, dehiscence, or requiring surgical intervention (n = 89). Controls
      were CABG patients without sternal wound complications (n = 267). The study
      examined 29 risk factors and 10 outcome variables. Univariate analysis on the
      risk factors revealed 10 significant risk factors. Logistic regression analysis
      was conducted and the risk factors that significantly predicted sternal wound
      complications after CABG surgery included older age (odds ratio [OR] = 0.85, 95%
      confidence interval [CI] 0.808-0.892), previous CABG surgery (OR = 3.9, 95% CI
      1.03-15.37), and in class three or four of the New York Heart Association
      functional class (OR = 2.8, 95% CI 1.27-6.12). There was a significant difference
      between CABG patients with and without sternal wound complications on nine
      outcome variables. Of the 29 predictors of post-CABG sternal wound infections
      being examined, 10 proved to be significant. Further analysis demonstrated only
      three variables that significantly predicted sternal wound complications. Older
      age, previous CABG surgery, and class three or four of the New York Heart
      Association functional class predispose CABG patients to sternal wound
      infections.

PMID- 16808206
TI  - Surgical residents' perception of simulation training.
AB  - Laparoscopic surgical simulation is a valuable and validated training tool. We
      examined its perception and use among general surgery residents at our
      institution. Questionnaires were sent to all 29 general surgery residents with a
      93 per cent response rate. Residents were divided into junior residents (JR; PGY
      1-2) and senior residents (SR; PGY 3-5). JR spent more hours in the simulation
      center and completed their assigned tasks faster than SR (14 vs 52 days). Thirty
      three per cent of SR felt that simulation training should be limited to JR in
      contrast to only 8 per cent of JR. However, 93 per cent of residents agreed that
      the program improved their laparoscopic skills. Most residents feel that
      simulation training is essential and mandatory in current surgical residency (75%
      of JR and 67% of SR) and needs to be extended to open surgery (67% JR and 60%
      SR). Seventy-five per cent of JR, but only 13 per cent of SR, feel that
      residents' involvement in procedures should be based on performance in surgical
      simulation. JR ranked simulation training first in useful ways to learn new
      skills, whereas SR ranked proctorship highest. JR have a higher use of simulation
      training and a higher perception of its utility.

PMID- 16808207
TI  - Recurrent asystole resulting from high cervical spinal cord injuries.
AB  - Cervical spinal cord injury is a highly morbid condition frequently associated
      with cardiovascular instability. This instability may include bradyarrhythmias,
      as well as hypotension, and usually resolves in a relatively short time. However,
      over a 3-year period (January 2003-December, 2005), 5 of 30 patients with
      complete cervical spinal cord injuries seen at our Level I trauma center required
      placement of permanent cardiac pacemakers for recurrent bradycardia/asystolic
      events. Strong consideration for pacemaker placement should be given for those
      spinal cord-injured patients with symptomatic bradyarrhythmic events still
      occurring 2 weeks after injury.

PMID- 16808208
TI  - Independent lung ventilation in the management of traumatic bronchopleural
      fistula.
AB  - Independent lung ventilation (ILV) is a technique for managing patients with
      unilateral lung disease or injury who have failed conventional mechanical
      ventilation. A 20-year-old man sustained severe ballistic injuries to the chest
      and abdomen. Damage control laparotomy controlled the patient's initial
      hemorrhage, however, an evolving cavitary pulmonary lesion subsequently developed
      into a high-volume bronchopleural fistula. Progressive atelectasis of the damaged
      lung resulted in profound hypoxemia and hypercarbia refractory to conventional
      mechanical ventilation. Synchronous ILV was initiated using a double-lumen
      endotracheal tube and two ventilators titrated to optimize the patient's
      oxygenation and ventilation and minimize ventilator-induced lung injury.
      Intensive ILV over the next 17 days resulted in recruitment of the atelectatic
      right lung, resolution of the bronchopleural fistula, and significant improvement
      in oxygenation and pulmonary compliance. This appears to be the longest reported
      use of ILV for traumatic lung injury.

PMID- 16808209
TI  - Treatment of pilonidal disease with laser epilation.
AB  - Pilonidal disease is a debilitating, chronic disease of the natal cleft. It
      mainly involves the sacrococcygeal region and the presentation varies from
      asymptomatic pits to painful draining abscesses. Treatment options vary from
      observation to wide excision. Unfortunately, surgical treatment often results in
      recurrence. The etiologic agent remains in question, as does the optimal
      treatment. Our objective was to assess the efficacy of laser epilation as an
      adjunctive therapy to surgical excision of the pilonidal sinus. Eighteen men and
      five women were treated with laser epilation in our office from 2001 to 2004. All
      patients had experienced recurrent folliculitis and had undergone some form of
      drainage procedure or prior excision. After surgical excision of the affected
      area, a Vasculite Plus laser was used for the epilation treatments. Each session
      involved 9 to 12 treatments and the patients underwent an average of two
      sessions. All 19 of the patients that remain in follow-up report no recurrence of
      their folliculitis or need for further surgical procedures. During treatment, six
      of the men and one of the women experienced a superficial wound dehiscence. All
      healed with local wound care and continued laser treatments. Laser epilation is
      an effective adjunctive therapy for the treatment of pilonidal disease. Although
      not curative in and of itself, the removal of hair allows better healing and
      decreases the chance of recurrence by removal of a significant etiology of
      pilonidal disease.

PMID- 16808210
TI  - Pediatric blunt trauma: a retrospective analysis in a Level I trauma center.
AB  - This study consisted of an 8-year retrospective trauma registry analysis of blunt
      trauma and comprised of 2458 children (<18 years of age) and 4568 adults (18-64
      years of age). Falls and motor vehicular crashes were seen in 30.4 per cent (749)
      and 23 per cent (566) of children, and 25.4 per cent (1158) and 41.9 per cent
      (1914) of adults. Children had a higher mean revised trauma score (7.69 vs 7.66)
      and Glasgow Coma Score (14.5 vs 14.3), and a lower Injury Severity Score (ISS;
      6.68 vs 7.83 and hospital length of stay (2.8 vs 3.8 days) with P < 0.05. Overall
      mortality was 1.3 per cent in children and 1.9 per cent in adults (P = 0.05).
      Pedestrian accidents resulted in a 3.8 per cent (6/161) mortality rate. Pediatric
      nonsurvivors had a 6.4-fold higher ISS than survivors compared with a 5.2-fold
      increase in adults. Mortality progressively increased with higher ISS; 0.09 per
      cent in <15, 1.3 per cent, in 15 to 24, and 17 per cent in children with > or =
      25 ISS. Mortality in multiple chest injuries was 19 per cent. The presence of
      chest trauma resulted in a 46-fold higher mortality in children. Most lethal
      injuries were combined head, chest, and abdomen trauma with a 25 per cent
      mortality in children and 28 per cent in adults. Admission Glasgow Coma Score <9
      and systolic blood pressure below 100 mm Hg carried high mortality: 39 and 6 per
      cent in children vs 31 and 24 per cent in adults. Ninety-seven per cent of
      children and 89 per cent of adults were discharged home.

PMID- 16808211
TI  - Peritoneocystic shunting for ascites.
AB  - The study was designed to determine if a prototype pump could be successfully
      implanted in the abdomen and effectively remove excess fluid without causing
      complications for a 1-month period. The procedure was performed on four swine
      under general anesthesia. A standard two-valve Denver shunt was implanted under
      the skin with the efferent limb implanted in the urinary bladder. The
      effectiveness of the pump was verified in vivo by pumping normal saline irrigated
      into the abdomen. The incision was closed and the animals were observed for any
      problems. After 1 month, a repeat test of the pump was performed. After this
      second test, the animals were euthanized and examined for complications of the
      device. All four swine survived the procedure and the 1-month follow-up. Pump
      function at the end of the 1-month interval was maintained in three of the four
      animals. None of the swine developed calculi. There were no consistent pathologic
      findings, although all four swine showed evidence of reactive inflammation at the
      insertion site of the efferent limb into the bladder. Preliminary data suggests
      that a subcutaneously implanted peritoneocystic shunt may be an option for the
      treatment of tense ascites.

PMID- 16808212
TI  - Video capsule endoscopy: clinical relevance of capsule endoscopy findings.
AB  - Video capsule endoscopy (VCE) is a novel diagnostic tool for noninvasively
      visualizing the lumen of the entire small intestine. It is especially useful in
      identifying the source of obscure small intestinal bleeding. However, VCE is not
      always optimal for localizing small bowel lesions. Several studies show VCE to be
      markedly superior to standard diagnostic techniques although the true clinical
      relevance of many of the capsule endoscopic findings remain unknown. We present
      two case reports of VCE findings that resulted in surgical intervention but were
      found to be benign lesions on definitive pathological examination. The actual
      clinical relevance of many of the lesions found on VCE thus remains to be
      demonstrated.

PMID- 16808213
TI  - Adrenal insufficiency in hemorrhagic shock.
AB  - Adrenal insufficiency during sepsis is well documented. The association between
      hemorrhagic shock and adrenal insufficiency is unclear and may be related to
      ischemia, necrosis, or resuscitation. This study was designed to determine the
      incidence of relative adrenal insufficiency in hemorrhagic shock. A retrospective
      review of a prospectively gathered database for patients admitted to the trauma
      intensive care unit with hemorrhagic shock was undertaken. A random serum
      cortisol of <25 mcg/dL defined relative adrenal insufficiency. All of the
      cortisol levels were drawn within the first 24 hours of admission. Data analyzed
      included demographics, length of stay, injury mechanism, infections, and
      mortality. Fifteen patients presented with hemorrhagic shock, with 14 of 15
      meeting the criteria for relative adrenal insufficiency. The average serum
      cortisol level was 15.8 (9-26.8). The average APACHE II score was 18.3 (4-33),
      and the average Injury Severity Score was 22.5 (8-41). The mechanism was blunt
      trauma in 10 patients and penetrating trauma in 5. The average intensive care
      unit and hospital length of stay were 13.2 and 27.4 days, respectively. There
      were five urinary tract infections, four blood stream infections, and two wound
      infections. Two of the 15 patients died. Relative adrenal insufficiency appears
      to be common in hemorrhagic shock. Future research is warranted to elucidate the
      pathophysiology, as well as to prospectively determine which patients may benefit
      from steroid replacement.

PMID- 16808214
TI  - Intraperitoneal hemorrhage in a patient with hepatic focal nodular hyperplasia.
AB  - Focal nodular hyperplasia (FNH) is a common benign liver tumor that is often
      confused with hepatic adenoma. Despite the benign course of both lesions, hepatic
      adenomas are associated with rupture and bleeding, and suggested management often
      includes prophylactic surgical resection. FNH lesions are thought to not rupture
      or bleed, and traditional management does not include resection. We report the
      case of a woman with FNH who presented with intraperitoneal hemorrhage after the
      rupture of a FNH lesion. Only six previous documented cases of hemoperitoneum
      associated with FNH have ever been reported. This report reviews all previously
      recorded cases of FNH lesions that have resulted in intraperitoneal hemorrhage.
      We suggest that although FNH is a benign lesion and intervention is typically
      unnecessary, the potential for rupture requiring surgical resection should always
      be considered.

PMID- 16808215
TI  - Anguishing over a spleen.

PMID- 16808216
TI  - Computed tomography follow-up imaging of stroke.
AB  - Due to its widespread availability, computer tomography (CT) scanning continues
      to be the primary initial imaging modality for assessment of patients with
      suspected acute stroke. It serves as a screening tool for other structural
      lesions which can mimic stroke and evaluates for possible hemorrhage prior to
      potential thrombolytic therapy. Findings seen on the initial CT may also serve as
      prognostic indicators of patient outcome helping with management decisions. As
      well, follow-up imaging in the subacute stages of infarct is also valuable for
      assessment of potential complications such as infarct extension, hemorrhagic
      transformation (and/or intracranial hemorrhage), and cerebral edema.

PMID- 16808217
TI  - Practical noninvasive neurovascular imaging of the neck arteries in patients with
      stroke, transient ischemic attack, and suspected arterial disease that may lead
      to ischemia, infarction, or flow abnormalities.
AB  - Stroke is the third leading cause of death in the United States, killing nearly
      157,000 people a year with an estimated society cost of dollar 58 billion in
      2006. A large percentage of ischemic strokes is secondary to extracranial carotid
      and vertebral arterial disease. While digital subtraction angiography has
      traditionally been used for the initial evaluation of the degree of stenosis,
      noninvasive imaging has moved to the forefront in the extracranial arterial
      evaluation. The importance of understanding the imaging techniques, findings,
      interpretation, artifacts, and pitfalls is essential to appropriate patient
      management.

PMID- 16808218
TI  - Using CT in the diagnosis and management of patients with cerebral vasospasm.
AB  - Cerebral vasospasm remains a serious complication of aneurysmal subarachnoid
      hemorrhage. Efforts in improving its clinical outcome have been focused on early
      diagnosis and applying effective treatment regimens. Standard diagnostic
      modalities currently used do not fully address this complex disease. The use of
      CT angiography and CT perfusion are discussed, with emphasis on its potential
      role in not only detecting vasospasm, but also in guiding management decisions
      and assessing clinical outcome.

PMID- 16808219
TI  - Computed tomography of pediatric stroke.
AB  - The causes of stroke in the children are varied. Magnetic resonance imaging (MRI)
      is generally accepted as the study of choice for definitive diagnosis of ischemic
      injury. However, often times MRI is not immediately available in the acute
      setting. This review highlights some of the major causes of stroke in children
      and the current role of computed tomography (CT), and more specifically, CT
      angiography in the pediatric setting.

PMID- 16808220
TI  - Stroke imaging with xenon-CT.
AB  - This article briefly reviews the current literature and implementation of a
      typically non-firstline methodology to diagnose acute stroke: inhalational
      mediated Xenon CT perfusion (Xe-CT). The intent of this article is to provide a
      short overview of this techniques; the reader is directed to the references for
      additional information.

PMID- 16808221
TI  - Computed tomographic angiography in stroke imaging: fundamental principles,
      pathologic findings, and common pitfalls.
AB  - The development of multidetector row computed tomography (MDCT) now permits
      visualization of the entire vascular tree that is relevant for the management of
      stroke within 15 seconds. Advances in MDCT have brought computed tomography
      angiography (CTA) to the frontline in evaluation of stroke. CTA is a rapid and
      noninvasive modality for evaluating the neurovasculature. This article describes
      the role of CTA in the management of stroke. Fundamentals of contrast delivery,
      common pathologic findings, artifacts, and pitfalls in CTA interpretation are
      discussed.

PMID- 16808222
TI  - Computed tomography angiography and computed tomography perfusion in ischemic
      stroke: A step-by-step approach to image acquisition and three-dimensional
      postprocessing.
AB  - Recent technical advances in both image acquisition and postprocessing have
      enabled computed tomography angiography (CTA) with computed tomography perfusion
      to become front-line tools for acute stroke evaluation in many institutions. This
      article provides a step-by-step approach to utilizing these technologies,
      particularly in the rapid triage of appropriate stroke patients to reperfusion
      therapies. The specific contrast injection, image acquisition, and 3D
      postprocessing protocols for high-quality CTA, currently in use at our
      institution, are delineated. An important point of emphasis is how preliminary
      angiographic and cerebral perfusion observations can be made immediately at the
      scanner to expedite emergent therapy. Also explored is the manner in which a
      dedicated 3D lab can support a high clinical volume, including a large percentage
      of emergent studies. An accurate yet time-efficient approach for the
      neuroradiologist to integrate 3D interpretation with CTA source data review is
      offered. Several important imaging and interpretive pitfalls in stroke CTA are
      illustrated.

PMID- 16808223
TI  - If veterinary service is to continue in rural Canada, fees must be increased.

PMID- 16808224
TI  - An ethicist's commentary on raising the legal status of animals.

PMID- 16808225
TI  - Proposed Canadian Voluntary National Johne's Disease Prevention and Control
      Program.

PMID- 16808226
TI  - Early history of the Canadian federal meat inspection service.

PMID- 16808228
TI  - Pig characteristics associated with mortality and light exit weight for the
      nursery phase.
AB  - One thousand and ten weaned pigs that were reared in 1 nursery in Iowa from
      weaning (17 +/- 2 days ) until 10 weeks of age were evaluated. A weaning weight
      threshold of 3.6 kg maximized the sensitivity and specificity to correctly
      predict the likelihood of dying or being light in weight at exit from the nursery
      (< or = 14.5 kg). Weaning weight < or = 3.6 kg (OR = 2.92), barrow (OR = 1.75),
      and sow unit (A versus B, OR = 2.14) were significant predictors of mortality in
      the nursery. Birth weight < or = 1.0 kg (OR = 2.66), weaning weight < or = 3.6 kg
      (OR = 8.75), gilt (OR = 1.4), sow unit (OR = 2.38), and gilt as nursing sow at
      weaning (OR = 1.66) were significant predictors of being lightweight at nursery
      exit. Eighteen per cent of the nursery deaths and almost half of lightweight
      nursery pigs could be prevented if there were no lightweight pigs at weaning.

PMID- 16808227
TI  - Equine gastrointestinal motility--ileus and pharmacological modification.
AB  - Colic is a common problem encountered in equine practice. Alteration of
      gastrointestinal motility is often the underlying cause for abdominal pain.
      Gastrointestinal motility can be measured as myoelectric activity, mechanical
      activity, and transit of intraluminal contents. Regulation of motility is based
      on a complex interaction between central innervation, autonomic innervation, and
      the enteric nervous system. Various humoral and neurochemical substances are
      required to interact flawlessly to allow propulsive motility. Ileus is defined as
      the absence of propulsive aboral movement of gastrointestinal contents,
      irrespective of its pathophysiology. Potential etiologies for ileus are described
      in this review. The prokinetic drugs available for clinical use are discussed.
      Choosing the appropriate prokinetic drug requires knowledge about the complex
      nature of gastrointestinal motility and its abnormalities.

PMID- 16808229
TI  - Prevalence of contagious mastitis pathogens in bulk tank milk in Prince Edward
      Island.
AB  - The purpose of this study was to 1) estimate the herd prevalence of contagious
      mastitis pathogens in bulk milk from Prince Edward Island (PEI) dairy farms, 2)
      determine the association between bulk milk culture results and mean bulk milk
      somatic cell count (BMSCC), and 3) investigate the agreement of repeated bulk
      milk cultures. Three consecutive bulk milk samples were obtained at weekly
      intervals from all 258 PEI dairy herds and were cultured using routine laboratory
      methods. Cumulative prevalence of Staphylococcus aureus, Streptococcus
      agalactiae, and Mycoplasma spp. (M. bovis and M. alkalescens) was 74%, 1.6%, and
      1.9%, respectively. Bulk milk somatic cell count of Staph. aureus-positive herds
      was higher than that of negative herds. Agreement for Staph. aureus isolation
      between 3 consecutive tests was moderate (kappa = 0.46). Mycoplasma bovis and M.
      alkalescens in bulk milk are being reported for the 1st time in PEI ever and in
      Canada since 1972.

PMID- 16808230
TI  - A comparison of serum harvesting methods and type of refractometer for
      determining total solids to estimate failure of passive transfer in calves.
AB  - Monitoring the passive transfer of immunoglobulins from colostrums particularly
      in noncentrifuged samples can be useful for calf health management programs. The
      results of total solids refractometry from centrifuge and noncentrifuge harvested
      sources of serum were highly correlated (R2 = 0.95). Results from a digital and a
      hand-held refractometer were highly correlated (R2 = 0.96).

PMID- 16808231
TI  - Cutaneous adverse reaction to furosemide treatment: new clinical findings.
AB  - A poodle was admitted for investigation of pruritus and a lesional pattern of
      erythema and alopecia located in the dorsolumbar area. After differential
      diagnosis ruling out several processes a rare side effect to furosemide, not yet
      described in canine medicine was confirmed as the possible causative agent.

PMID- 16808232
TI  - Oral ulceration and bleeding associated with pancreatic enzyme supplementation in
      a German shepherd with pancreatic acinar atrophy.
AB  - A 20-month-old German shepherd with primary pancreatic acinar atrophy and
      exocrine pancreatic insufficiency that was treated with pancreatic enzyme
      supplementation, vitamin B12, and cimetidine developed oral bleeding. Following
      discontinuation of the cimetidine, increased preincubation of the enzymes with
      the food, and symptomatic therapy for the ulceration, the dog's condition
      improved.

PMID- 16808233
TI  - Sebaceous adenitis in a 7-year-old Arabian gelding.
AB  - A 7-year-old Arabian gelding was presented with a 9-month history of progressive
      patches of nonpruritic scaling, crusting, alopecia, and leukoderma of the
      periocular areas and muzzle, becoming generalized over time. Sebaceous adenitis
      was diagnosed on histopathologic examination. Lesions resolved without treatment,
      coinciding with regression of a sarcoid on the neck.

PMID- 16808234
TI  - Animal-dependent veterinary staff: too much of a good thing.

PMID- 16808235
TI  - More orthopedic bits and pieces.

PMID- 16808236
TI  - Veterinary diagnostic imaging.Thymoma.

PMID- 16808238
TI  - RAPD analysis of genetic diversity and population genetic structure of Stipa
      krylovii Reshov. in Inner Mongolia steppe.
AB  - Random amplified polymorphic DNA (RAPD) analysis was used to characterize the
      genetic diversity and population genetic structure of Stipa krylovii populations
      in Inner Mongolia steppe of North China. Thirteen 10 bp oligonucleotide primers,
      which generated 237 RAPD bands, were used to analyze 90 plants of five
      populations from three regions, meadow steppe, typical steppe and desert steppe,
      from the east to the west. The genetic diversity of Stipa krylovii that was
      revealed by observed number of alleles (na), expected number of alleles (ne),
      Nei's diversity index (h), Shannon's diversity index (H), amplificated loci,
      polymorphic loci and the percentage of polymorphic loci (PPB) increased from the
      east to the west. The Pearson's correlation analysis between genetic diversity
      parameters and ecological parameters indicated that the genetic diversity of
      Stipa krylovii was associated with precipitation and cumulative temperature
      variations along the longitude (humidity were calculated by precipitation and
      cumulative temperature). Dendrogram based on Jaccard's genetic distance showed
      that the individuals from the same population formed a single sub-group. Although
      most variation (56.85%) was within populations, there was high genetic
      differentiation among populations of Stipa krylovii, high differentiation within
      and between regions by AMOVA analysis. Either Nei's unbiased genetic distance
      (G(ST)) or gene flow (Nm) among pairwise populations was not correlated with
      geographical distance by Mantel's test (P > 0.05), suggesting that there was no
      consistency with the isolation by distance model in these populations. Natural
      selection may have played a role in affecting the genetic diversity and
      population structure, but habitat destruction and degradation in northern
      grassland in China may be the main factor responsible for high genetic
      differentiation among populations, within and among regions.

PMID- 16808237
TI  - [Analysis of genetic variation in unisexual and bisexual lizard species of the
      genus Leiolepis from Southeast Asia].
AB  - Using multilocus DNA fingerprinting with microsatellite probes (CAC)5, (GACA)4,
      (GGCA)4 and (GATA)4, intraspecific variation of the Southeast Asian lizards
      belonging to the genus Leiolepis (bisexual species Leiolepis reevesii and
      triploid parthenogenetic species Leiolepis guentherpetersi) was first examined.
      The L. guentherpetersi lizards were characterized by monophyletic DNA fingerprint
      profiles for the loci detected by the (GACA)4, (GGCA)4, and (CAC)5 probes, in
      terms of intrapopulation similarity index constituting S = 0.96. This was
      different from the individual-specific profiles of the lizards from bisexual,
      presumably parental species, L. reevesii (S = 0.6; P < 0.001). Genetic
      homogeneity of triploid L. guentherpetersi lizards at the loci examined serves as
      one of the arguments for the parthenogenetic nature of this species. Genetic
      variability of triploid parthenogenetic species L. guentherpetersi appeared to be
      comparable with that reported earlier for the Caucasian rock lizards of the genus
      Darevskia, namely, D. dahlia, D. armeniaca, and D. unisexualis (P > 0.05). The
      results of DNA fingerprinting analysis of the same L. guentherpetersi samples
      with the (GATA)4 hybridization probe were unexpected. Variability of
      parthenogenetic species L. guentherpetersi at the (GATA)n markers was remarkably
      higher than that at other DNA markers (S = 0.35; P = 3.08 x 10(-11)), being
      comparable to the variation of the (GATA)n DNA markers in bisexual species L.
      reevesii (P = 0.74). The reasons for high polymorphism of the (GATA)n-containing
      loci in L. guentherpetersi still remain unclear. This polymorhism is probably
      associated with high instability of the loci, which can be revealed by means of
      family analysis of parthenogenetic offspring.

PMID- 16808239
TI  - IncP plasmids are most effective in mediating conjugation between Escherichia
      coli and streptomycetes.
AB  - Mobilizable shuttle plasmids containing the origin of transfer (oriT) region of
      plasmid F (IncFI), ColIb-P9 (IncI1), and RP4/RP1 (IncPalpha) were constructed to
      test the ability of the cognate conjugation system to mediate gene transfer from
      Escherichia coli to Streptomyces. The conjugative system of the IncPalpha
      plasmids was shown to be most effective in conjugative transfer, giving peak
      values of (2.7 +/- 0.2) x 10(-2) S. lividans TK24 exconjugants per recipient
      cell. To assess whether the mating-pair formation system or the DNA-processing
      apparatus of the IncPalpha plasmids is crucial in conjugative transfer, an assay
      with an IncQ-based mobilizable plasmid (RSF1010) specifying its own DNA
      processing system was developed. Only the IncPalpha plasmid mobilized the
      construct to S. lividans indicating that the mating-pair formation system is
      primarly responsible for the promiscuous transfer of the plasmids between E. coli
      and Streptomyces. Dynamic of conjugative transfer from E. coli to S. lividans was
      investigated and exconjugants starting from the first hour of mating were
      obtained.

PMID- 16808240
TI  - [Analysis of mutations in the mat1 region of Schizosaccharomyces pombe strain
      with the deletion of gene rhp55+].
AB  - DNA double-strand breaks may occur both under the action of various exogenous
      factors and in the course of cell metabolism processes, in particular, upon
      mating type switching in yeast. Genes belonging to the epistatic group RAD52 are
      known to repair such DNA damage. Molecular defects in mating type switching
      occurring after the deletion of gene rhp55+ encoding the paralog of
      recombinational protein Rhp51, which is a functional homolog of Escherichia coli
      RecA, were studied in fission yeast. Analysis of stable nonswitching segregants
      in h90 rhp55 mutants with unchanged configuration of the mating type switching
      locus but with a drastically decreased level of double-strand DNA break formation
      at the mat1 :1 locus demonstrated changes in DNA sequences within the region
      responsible for the generation of the breaks. These changes might have resulted
      from incorrect gene conversion upon repair of double-strand DNA breaks in
      Schizosaccharomyces pombe rhp55 mutants.

PMID- 16808241
TI  - [Dependence of the carcinogenicity of nitro compounds on their structural
      characteristics].
AB  - A new approach to the description of quantitative structure-activity
      relationships (QSAR analysis) based on compound descriptors has been used. The
      effect of the structural characteristics of nitric compounds on their
      carcinogenicity has been studied. It has been found that the carcinogenicity of
      nitric compounds is determined by the presence of furyl and/or azole heterocycles
      not condensed with benzene rings in their molecular structures. The
      carcinogenicity of the nitric compounds in which the benzene ring is the basic
      structure is determined by the presence of other substituents (halogens, amines,
      and methyl groups) and their positions relative to the nitro group.

PMID- 16808242
TI  - [Factors of maintaining chromosome polymorphism in common vole Microtus arvalis
      Pallas, 1779: reduced fertility and meiotic drive].
AB  - The common vole Microtus arvalis (the form obscurus) exhibits polymorphism of a
      pericentric inversion in chromosome pair 5 throughout the species range. In the
      Urals populations, the frequency of an acrocentric variant of the heteromorphic
      chromosome is very low (on average 3.2%) and virtually does not change annually.
      The factors of maintaining stable chromosomal polymorphism in the common vole
      were studied under conditions of a laboratory colony. Heterozygous and homozygous
      for the acrocentric chromosome females showed a significant reduction of the
      reproductive output irrespective of the male karyotype. This effect was
      manifested mostly in litter size at birth. A number of cytogenetic and
      exophenotypic characteristics, as well as parent--offspring transmission of this
      chromosome in crosses of various types, were examined. We have found meiotic
      drive in favor of the acrocentric, as a result of which the frequency of the
      acrocentric (without taking into account the postnatal mortality) totaled over
      all cross variants (0.48) was significantly higher than that expected with random
      segregation (0.42). It is likely that meiotic drive of the acrocentric largely
      compensates for the reduced fertility of its carriers, being among the factors of
      maintaining it in natural populations.

PMID- 16808243
TI  - [Evaluation of the state of the gene pool of natural populations of vertebrate
      animals inhabiting the fragmented landscape of Moscow and Moscow district (with
      special reference to brown frogs)].
AB  - A system of urban ecological genetic monitoring has been developed for the first
      time in Russia and in the world. As a model, two species of brown frogs, Rana
      arvalis Nilss. and R. temporaria L. (16 populations, seven isozyme loci) were
      used. An evaluation of the gene pool state in urban frog populations has shown
      that the diversity in the Moscow frog populations was lower than that in natural
      populations (up to 80 and 50% in respectively R. anvalis and R. temporaria). Mean
      heterozygosities per locus were higher in large natural populations than in small
      urban isolates: in R. arvalis, these values were 0.16 and 0.06; in R. temporaria,
      0.34 and 0.18, respectively. The number of polymorphic loci was also higher in
      natural populations than in the urban ones: 4 versus 2 in R. arvalis and 5 versus
      4 in R. temporaria. Using superoxiddismutase as an example, fixation of different
      alleles of the same locus in different small isolates was shown. The gene pool
      condition of all but one urban populations of brown frog was evaluated as
      unsatisfactory, and that of the R. arvalis populations, as critical. These
      changes of the gene pool are explained mainly by gene drift accompanied by
      inbreeding, which was caused by human-induced fragmentation of the range and a
      decrease in population size of the species. The results of this study was
      employed in the development of the Moscow governmental program on restoration of
      the gene pools of vanishing animal species on specially protected natural urban
      territories. The series of works on long-term monitoring and assessment of the
      state of natural populations of model species in anthropogenic landscapes of
      Moscow and Moscow district has laid a foundation for a new branch of science,
      gene urbanology.

PMID- 16808244
TI  - [A change in the stability of marker nptII and uidA gene expression in transgenic
      tobacco plants].
AB  - A comparative analysis of variability of heterologous gene expression was
      conducted in original (T0) transgenic tobacco plants, differing with respect to
      the copy number of uidA gene (a single and two copies as a direct duplication)
      within the T-DNA insertion, and among progenies obtained by their self
      pollination (T1). Variability of beta-glucuronidase enzyme activity was shown in
      original transgenic plants or among progenies of the first generation in both
      groups. It is established that the activity level of beta-glucuronidase among T0
      plants with a duplication of the uidA gene is significantly higher (21.9 times)
      than that determined in transformants with a single-copy gene. In T1 progenies of
      plant 16.40, carrying a duplication of the uidA gene, a drastic decrease in
      enzyme activity was observed, which correlated with a decrease or absence of mRNA
      transcripts, pointing to a disturbance in reporter gene expression. Alterations
      in the functioning of another heterologous gene (nptII) within the same T-DNA
      insertion were not observed among progenies of transgenic plant 16.40.

PMID- 16808246
TI  - [Age dynamics of genetic variation in an isolated population of chalk pine Pinus
      sylvestris var. cretacea Kalenicz. ex Kom. from Donbass].
AB  - Based on analysis of variation at ten allozyme loci in three age groups (25-35,
      40-80, and more than 100 years of age) of plants and in seed embryos, demographic
      dynamics of the gene pools was studied in a small (60.5 ha) isolated relict
      population of chalk pine Pinus sylvestris var. cretacea Kalenicz. ex Kom. from
      the steppe zone of Ukraine. The observed grenotype proportions in these tree
      groups were shown to fit Hardy-Weinberg expectations, while in the embryos of
      their seeds, an excess of homozygotes was observed at five to nine loci. The mean
      observed heterozygosity in the sample of old (> 100 years of age) trees (H(O) =
      0.225) was substantially lower than in trees of the two other age groups (H(O) =
      0.307; 0.311), but significantly higher than in the corresponding embryo samples
      (H(O) = 0.183-0.207). No allele and genotype heterogeneity of the maternal trees
      and embryos of their seeds was found. However, heterogeneity was high when the
      progeny of trees of different ages, particularly in pairs with old trees, were
      compared.

PMID- 16808245
TI  - [The effect of duplications in the T-DNA on the stability of manifestation of
      heterologous genes in transgenic tobacco plants].
AB  - The duplication of uidA gene within T-DNA was shown to disturb stability of
      expression of another marker gene, nptII, in the second generation (T2) of selfed
      initial transformants and in F1 hybrids of the crosses with nontransgenic
      tobacco. Hybridological analysis of the progeny resulting from various crosses
      involving T1 plants demonstrated that the expression of nptII gene was impaired
      in the hybrids that were hemizygous for the inactivated copy of uidA gene.

PMID- 16808247
TI  - [Differentiation of closely related oyster fungi Pleurotus pulmonarius and P.
      ostreatus by mating and molecular markers].
AB  - Classical matings and RAPD-PCR analysis were used to differentiate two closely
      related basidial fungi, Pleurotus pulmonarius and P. ostreatus, which are
      widespread in Russian forest biocenoses with moderate climate. Monokaryon
      monokaryon (mon-mon) and dikaryon--monokaryon (di-mon) matings demonstrated
      complete reproductive isolation of the two species, which have partly overlapping
      morphological traits. The prevalence of a particular species in nature was shown
      to depend to a great extent on the natural conditions, namely, the day and night
      temperature ranges. The clustering of natural Pleurotus strains displayed two
      trends: one was associated with natural reproductive isolation of the two species
      (D = 0.61) and the other, with the geographical factor (D = 0.39). A relatively
      recent origin is suggested for the divergence of the two species and the
      reproductive barrier between them. Adaptation to natural conditions was
      considered to be the main factor causing the divergence of natural Pleurotus
      populations and, eventually, allopatric speciation.

PMID- 16808248
TI  - [Identification of leaf rust resistance genes in wheat (Triticum aestivum L.)
      cultivars using molecular markers].
AB  - A collection of 68 cultivars of common wheat has been screened for leaf rust
      resistance genes with the use of molecular markers. Markers of genes Lr1, Lr9,
      Lr10, Lr19, Lr20, Lr21, Lr24, and Lr26 have been used. It has been suggested that
      allele Xgwm295 be used as a marker for identifying the Lr34 gene. The genes
      originating from Triticum aestivum L., as well as the Lr26 gene contained in rye
      translocation 1RS, are the most frequent. Genes originating from wild wheats were
      rarer in the cultivars studied.

PMID- 16808249
TI  - [The effect of the duration of callus culture on the accumulation of genetic
      alterations in regenerated pea Pisum sativum L].
AB  - Two groups of regenerant plants were obtained from different pea genotypes (lines
      R-9 and W1 and cultivar Viola). The first group was derived after eight months of
      culture and the second, from calluses cultured for a prolonged (more than ten
      years) time. Using random amplified polymorphic DNA (RAPD) and inter simple
      sequence repeats (ISSR) methods, the regenerants and the original lines were
      compared with regard to genetic differences. The regenerants from both groups
      were shown to differ in DNA polymorphism from the original lines and from one
      another. The divergence of the regenerants was also different, depending largely
      on the original genotype. Examination of genetic differences between the first
      and the second group showed that the variability increased with culturing time.
      This was particularly evident for regenerants of the Viola cultivar, in which
      variability ranged from 0-5% (first group of regenerants) to 10% (second group of
      regenerants).

PMID- 16808250
TI  - [Comparative study of the population structure and population assignment of
      sockeye salmon Oncorhynchus nerka from West Kamchatka based on RAPD-PCR and
      microsatellite polymorphism].
AB  - Using two types of molecular markers, a comparative analysis of the population
      structure of sockeye salmon from West Kamchatka as well as population assignment
      of each individual fish were carried out. The values of a RAPD-PCR-based
      population assignment test (94-100%) were somewhat higher than those based on
      microsatellite data (74-84%). However, these results seem quite satisfactory
      because of high polymorphism of the microsatellite loci examined. The UPGMA
      dendrograms of genetic similarity of three largest spawning populations,
      constructed using each of the methods, were highly reliable, which was
      demonstrated by high bootstrap indices (100% in the case of RAPD-PCR; 84 and
      100%, in the case of microsatellite analysis), though the resultant trees
      differed from one another. The different topology of the trees, in our view, is
      explained by the fact that the employed methods explored different parts of the
      genome; hence, the obtained results, albeit valid, may not correlate. Thus, to
      enhance reliability of the results, several methods of analysis should be used
      concurrently.

PMID- 16808251
TI  - Micronucleus frequency in peripheral blood lymphocytes and exfoliated buccal
      cells of untreated cancer patients.
AB  - Some genetic diseases may increase the cellular instability. Since most human
      tumors have some genetic base, this study was undertaken for the genetic
      instability in cancer patients by micronucleus analysis, a mutation-screening
      test, which is more practical and economic technique than metaphase analysis
      carried out for chromosomal aberrations. Genetic changes were assessed in
      untreated cancer patients (lung, stomach and colon cancer) by different
      genotoxical screening methods; the cytokinesis-block micronucleus test and the
      buccal mucosa cell micronucleus test. The evaluation of micronuclei number in
      peripheral blood lymphocytes and buccal cells showed a genomic instability in
      somatic cells. There was a significant increase in the number of micronuclei in
      cancer patients prior to the initiation of chemotherapy, and/or radiotherapy
      compared with healthy human subjects. Furthermore, there was no significant
      difference between smokers and non-smoking groups or male and female groups.
      These results suggest that cancer in humans is characterized by an increase of
      chromosomal damage and thus, the micronucleus assay carried out here may be
      useful in routine cytogenetic studies of cancer.

PMID- 16808252
TI  - [Frequencies of C677T and A1298C polymorphisms of methylenetetrahydrofolate
      reductase gene at the early stage of human individual development].
AB  - In most cases, the cause of embryo and fetus death remains unclear although the
      multifactorial causes are suspected. The polymorphic C677T and A1298C variants of
      the MTHFR gene are associated with an increase in the level of homocysteine,
      which is risk factor of pregnancy loss. The subject of this study is analysis of
      genotypes and haplotypes of C677T and A1298C polymorphic variants of MTHFR genes
      in the groups of spontaneous abortions with the normal karyotype and newborns in
      the Tomsk population. Between these groups, no statistically significant
      differences were determined in the allele, genotype, and haplotype distributions
      of C677T and A1298C polymorphisms of the MTHFR gene. The haplotype frequencies of
      C677T and A1298C polymorphic variants of MTHFR gene in the Russian populations,
      which proved to be similar to those in most European populations, are presented.

PMID- 16808253
TI  - [Advances in the quality of life related with health and renal transplantation].

PMID- 16808254
TI  - [Clinical research based nephrology (bases for the constitution of an Evidence
      Based Nephrology Group in the Spanish Society of Nephrology)].

PMID- 16808255
TI  - [Refractory acute rejection in the fourth renal transplantation].

PMID- 16808256
TI  - [Impact of immunossuppression in the cardiovascular risk profile after renal
      transplantation I].

PMID- 16808257
TI  - [What are the Hox genes? Its importance in vascular and renal disease].

PMID- 16808258
TI  - [Relationship between renal function and bone mineral density in postmenopausal
      women that undergo bone mass evaluation].
AB  - As osteoporosis and renal insufficiency are two prevalent pathologies in the
      aging population we decided to evaluate retrospectively the renal function
      (estimated by formula) in postmenopausal women who came to our Institute for bone
      mass determination to establish the relationship between them. Thus, we studied
      300 postmenopausal women with a mean age of 66.9 +/- 6.8 years who had a bone
      densitometry performed; we chose total femur bone mineral density (TFBMD) for
      defining osteopenia and osteoporosis as this measurement included substantial
      amounts of both trabecular and cortical bone; osteopenia/osteoporosis was
      diagnosed using T score criteria recommended by the WHO. We also measured BMD at
      the femoral neck. Renal function was estimated by the Cockcroft-Gault formula
      using serum creatinine determination. We found osteoporosis in 61 patients
      (20.3%). Of them, el 81.9% have renal insufficiency (estimated creatinine
      clearance-ECrC < or = 60 ml/min), compared to 54% of 239 women who had normal
      BMD/osteopenia (p < 0.001). Six of 61 (9.8%) women with osteoporosis had severe
      renal insufficiency (ECrC < or = 36 ml/min) versus 4/239 (1.6%) women with normal
      BMD/osteopenia (p = 0.001). Women with osteoporosis were older, and had a
      significantly lower weight and ECrC compared to patients without osteoporosis
      (ECrC 52 +/- 11 ml/min vs 59 +/- 12 ml/min; p < 0.0001). We found a significant
      positive correlation between TFBMD and ECrC (r = 0.389) as well as with weight (r
      = 0.422) and a negative correlation between age and ECrCE (r = -0.51) and with
      TFBMD (r = -0.22). In the multiple regression analysis only weight continued to
      correlate significantly with TFBMD (Beta = 0.344). When FNBMD was considered as
      the dependent variable, we found a significantly negative correlation with age (r
      = -0.30) and significantly positive correlations with height (r = 0. 16), weight
      (r = 0.33) and ECcr (r = 0.39). In the multiple regression analysis only age
      (Beta = -0.20) and weight (Beta = 0.20) continued having an independent
      correlation FNBMD. We conclude that our data confirm that there exists a
      substantial prevalence of renal insufficiency, even severe, among patients with
      densitometric osteoporosis that should be kept in mind when one is considering
      the prescription of medications as bisphosphonates that have renal clearance, so
      as not to jeopardize the efficacy and the security of these drugs.

PMID- 16808259
TI  - [Renal involvement in amyloidosis. Clinical outcomes, evolution and survival].
AB  - BACKGROUND: Systemic amyloidosis is a disease resulting from extracellular
      deposition of fibrillar protein in various organs. Main systemic amyloidosis are:
      primary (AL) and Secondary (AA). The kidney is usually involved, conferring and
      adverse prognosis. In the last decade there has been a change in the aetiology of
      AA amyloidosis. OBJECTIVES: To analyse the incidence of AL and AA amyloidosis in
      our current population as well as the aetiology of AA amyloidosis. To describe
      clinical outcomes, renal involvement and survival. PATIENTS AND METHODS: We
      performed a descriptive analysis of all cases of amyloidosis diagnosed from 1992
      to 2004 in our hospital. Diagnosis was assessed on histological criteria:
      positivity Congo Red stain. Clinical data, renal involvement, dialysis treatment
      and survival were analysed. RESULTS: 76 cases, 44 women, mean age 70.7 +/- 12.
      Types: 55 AA (72%), 21 AL (28%) systemic amyloidosis. AA aetiology was: 66%
      rheumatic disorders, 28% infectious disease, 6% others. Incidence for AL was 4.6
      and for AA 12.2 cases/million. Renal involvement was present in 75% at diagnosis
      (69% Creatinine clearance < 60 ml/min, 37% urinary protein > 3 g/24 hours). 21
      cases (28%) progressed to renal disease stage V in the 8.1 +/- 9.8 months follow
      up period, and 14 cases started dialysis treatment (10 HD, 4 CAPD). In 7 cases
      (33%) dialysis was not indicated due to their poor clinical condition, short life
      expectancy and bad quality of life. Mean global survival at diagnosis was 55% and
      40% at 12 and 24 months (AL 58% and 19%; AA 55% and 44%). Mean survival from the
      start of dialysis was 30% and 5% at 12 and 24 months. CONCLUSIONS: Although
      amyloidosis has a low incidence in our population, the kidney is usually
      involved. Rheumatological disorders are the principal aetiology of AA
      amyloidosis. Long term survival is poor, specially for AL.

PMID- 16808260
TI  - [Effect of oxidative stress in patients with chronic renal failure].
AB  - BACKGROUND: Cardiovascular disease remains the single most common cause of excess
      morbidity and mortality in end-stage renal disease (ESRD) patients and the
      traditional risk factors can't explain the high incidence of these events. New
      "non-traditional" risk factors are analysed in uremic patients and the increased
      oxidative stress is postulated to be an important contributor to uremic
      cardiovascular risk. METHODS: In order to evaluate the effects of the
      hemodialysis treatment, a complete oxidative stress study was performed in
      fifteen uremic patients. Representative antioxidant enzymes such as superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), together with
      oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators
      including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG), were
      analysed to assess oxidative stress status in normal control volunteers and in
      uremic patients treated with hemodialysis (HD). In the latter group blood samples
      were taken prior and after HD to evaluate the effect of the session of HD over
      the oxidative markers. RESULTS: Low levels of antioxidant enzyme activities were
      observed in the uremic patients as compared with normal control subjects. HD
      treatment results in a significant recovery of these enzyme activities but remain
      lower as compared with control values. Levels of GSSG and GSH concentrations were
      increased and reduced respectively in uremic patients. These differences were
      even higher before the HD and were reduced upon treatment to levels closer to
      those observed in controls. MDA levels and 8-oxo-dG levels were also increased in
      uremic patients with the highest values observed in the pre-treated HD group.
      Even though HD treatment decreases the levels of oxidation products in
      mononuclear cells of uremic patients the values of the control group are not
      reached. CONCLUSIONS: Our results suggest that hemodialysis by itself could
      correct the oxidative status in these patients. The possible mechanisms involved
      in the oxidative stress changes with the hemodialysis treatment will be discussed
      below.

PMID- 16808261
TI  - [A long-term comparative study of calcitriol versus alphacalcidol in patients
      with secondary hyperparathyroidism on hemodialysis].
AB  - Calcitriol has traditionally been the most widely used treatment for secondary
      hyperparathyroidism (SHPT) in uremic patients. There are currently no crossover
      equivalence studies of alphacalcidol versus calcitriol establishing which of the
      two derivatives is more active and better tolerated. The objective of this study
      was to compare the long term effect on control of PTH of similar doses of
      alphacalcidol versus calcitriol in the treatment of SHPT in these patients.
      METHODS: We conducted a retrospective study on 21 hemodialysis patients with
      stable SHPT of varying severity treated with intravenous calcitriol. In July
      2002, the pharmacy of the reference hospital decided to substitute calcitriol for
      alphacalcidol based on the similarity of the two drugs. The conversion was made
      substituting a similar amount of drug. Mean absolute serum levels and percentage
      change in PTH, calcium and phosphorus were compared between the two periods and
      at 0, 3, 6, 9, 12 and 15 months after starting treatment with alphacalcidol.
      Student's t-test for paired means was used to compare the values between the two
      periods. RESULTS: In the calcitriol period, mean PTH levels were 275.2 +/- 111.7
      pg/ml. The mean dose of drug used was 1.7 +/- 0.8 mcg postdialysis, and serum
      calcium and phosphorus levels were 10.1 +/- 0,5 mg/dl and 5,2 +/- 0,9 mg/dl,
      respectively (p < 0.01). Mean dialysate calcium content was 2,9 +/- 0,3 mEq/l. In
      the alphacalcidol period, PTH increased (441.6 +/- 178.3 pg/ml) (p < 0.001) and
      the percentage of patients with PTH < 300 pg/ml decreased (24% at the end of the
      period), in spite of significantly increasing the mean drug dose (2,3 +/- 0,9 mcg
      postdialysis) (p < 0.05). Serum calcium levels did not show significant
      differences (10.2 +/- 0.7 mg/dl) (p = NS), but phosphorus control was improved
      (4,7 +/- 0,5 mg/dl) (p < 0.01). The percentage of patients with PTH < 300 pg/ml
      decreased progressively from the start of treatment with alphacalcidol from 75%
      to 24% at the end of follow-up. Our results seem to suggest that the dose of
      alphacalcidol and calcitriol are not equivalent and we need to increase the dose
      of alphacalcidol to obtain a similar result to calcitriol on suppression of PTH
      in uremic patients with SPTH.

PMID- 16808262
TI  - [Quality control systems implementation in the Spanish Dialysis Units].
AB  - OBJECTIVE: The aim of this study was to evaluate and analyze the implementation
      of a Quality Management Systems (QMS) and the use of Clinical Performance
      measures by the Nephrology Services and Hemodialysis Units in Spain. METHOD: The
      Quality Management Work Group of the Spanish Society of Nephrology (SEN) realized
      a survey that was directed to all the Spanish Nephrology Services and
      Hemodialysis Units. No exclusion criteria were defined for the study. The survey
      was based on a multichotomous self completing "Ad Hoc" questionnaire. RESULTS:
      The survey was answered by 46.7% of the polled centers (44.5% were public
      hospitals and 55.5% private centers). Of those replying the survey 70 % had a
      QMS, with a higher implementation in the area of Hemodialysis (HD). The ISO 9001
      2000 was the prefer QMS model chosen by 76.4% of the centers. 68.6% of the
      centers with a QMS were certified by an external Auditing Group. 91.7% of the
      Nephrology Services and Hemodialysis units were using some clinical practice
      guideline. A high percentage of the centers had medical protocols and nursing
      plans (> 90%). A significantly higher implementation of QMS was observed in
      Private Hospitals and Hemodialysis Units (88.8 %) when compared to public
      Hospitals (46.1%) (X2: 31.5; p < 0.001). The ISO 9000 Standard certification was
      selected by 78,3% of the private centers and by 21,7% of the public centers (X2:
      37.3; p < 0.001). The certification or accreditation were done by an external
      auditing group in 68. 1% of the private centers compared to 31.9% for the public
      Hospitals (X2: 24.8; p < 0.001). Although the rate of answers prevents from
      extracting definitive conclusions, the result seems to indicate that in the
      Spanish Nephrology Community a clear trend exists towards the use QMS. This
      tendency suggests, that in the near future, there will be a progressive
      implementation and routine use of QMS in the Nephrology Community in Spain.

PMID- 16808263
TI  - [Determination of the dose of dialysis with integrated modules in the same
      monitor].
AB  - The "gold standard" method to measure the mass balance achieved during dialysis
      for a given solute is based on the total dialysate collection. This procedure is
      unfeasible and too cumbersome. For this reason, alternative methods have been
      proposed including the urea kinetic modelling (Kt/V), the measurement of
      effective ionic dialysance (Diascan), and the continuous spent sampling of
      dialysate (Quantiscan). The aim of this study was to compare the reliability and
      agreement of these two methods with the formulas proposed by the urea kinetic
      modelling for measuring the dialysis dose and others haemodialysis parameters. We
      studied 20 stable patients (16 men/4 women) dialyzed with a monitor equipped with
      the modules Diascan (DC) and Quantiscan (QC) (Integra. Hospal). The urea
      distribution volume (VD) was determined using anthropometric data (Watson
      equation) and QC data. Kt/V value was calculated according to Daurgidas 2nd
      generation formula corrected for the rebound (eKt/V), and using DC (Kt/VDC) and
      QC (Kt/VQC) data. The total mass of urea removed was calculated as 37,93 +/- 16
      g/session. The VD calculated using Watson equation was 35.7 +/- 6.6 and the VDQC
      was 35.06 +/- 9.9. And they showed an significative correlation (r:0,82 p <
      0.001). The (VDQC-VDWatson) difference was -0.64 +/- 5.8L (ns). Kt/VDC was
      equivalent to those of eKt/V (1.64 +/- 0.33 and 1.61 +/- 0.26, mean difference 
      0.02 +/- 0.29). However, Kt/VQC value was higher than eKt/V (1.67 +/- 0.22 and
      1.61 +/- 0.26 mean difference 0.06 +/- 0.07 p < 0.01). Both values correlated
      highly (R2: 0.92 p < 0.001). Urea generation (C) calculated using UCM was 8.75 +/
      3.4 g/24 h and those calculated using QC was 8.64 +/- 3.21 g/24 h. Mean
      difference 0.10 +/- 1.14 (ns). G calculated by UCM correlated highly with that
      derived from QC (R2: 0.88 p < 0.001). In conclusion, Kt/VDC and Kt/VQC should be
      considered as valid measures for dialysis efficiency. However, the limits of
      agreement between Kt/VQC and eKt/V were closer than Kt/VDC.

PMID- 16808264
TI  - [Renal transplantation in the northwest of Spain: analysis of the activity in the
      region of Galicia].
AB  - BACKGROUND: Spain is the world leader in organ transplant rates, and the national
      average is maintained in the northwestern Spanish region of Galicia. However,
      there is no official registry recording transplantation results in this region.
      In this paper we report a study of patient and graft survival and risk factors
      among kidney transplant patients in Galicia between January 1996 and December
      2000. METHODS: Patients receiving kidney transplants in Galicia in the above
      period were monitored up to the end of 2001, deaths and graft losses were
      recorded and analysed by actuarial and Kaplan-Meier methods, and possible risk
      factors for death and graft loss were evaluated using Cox's proportional hazards
      model. RESULTS: In the study period, 672 kidneys were transplanted, all from
      deceased donors. Graft and patient survival rates were respectively 80% and 94%
      after 1 year, and 67% and 83%, after 5 years. Two-thirds of graft losses occurred
      within the first year and the most common cause was vascular thrombosis (44%).
      Independent risk factors for graft loss were donor asystole (relative risk [RR] =
      3.41, 95% confidence interval [CI]: 1.73-6.73), donor age (RR = 1.54, CI: 1.05
      2.27 for 40-60-year-olds, RR = 2.59, CI: 1.66-4.07 for over-60s, relative to
      under-40s), donation from outside the institution in which implant was performed
      (RR = 1.43, CI: 1.02-2.02), acute rejection (RR = 2.32, CI: 1.63-3.22), and
      retransplantation (RR = 1.56, CI: 1.03-2.37). The main causes of death were
      infections (38%), followed by cardiovascular pathologies (30%) and tumours (11%).
      CONCLUSIONS: The kidney transplant rate varies excessively within Galicia; the
      global rate is 50 per million inhabitants per year. Patient survival is similar
      to those recorded in national registers, but graft survival is deficient,
      apparently due to a high incidence of vascular thrombosis.

PMID- 16808265
TI  - [Renal transplantation with positive crossmatch].
AB  - INTRODUCTION: Lymphocytotoxic antibodies reduce the expectancy of renal
      transplantation due to the increased risk of a positive crossmatch. MATERIAL AND
      METHODS: We analyzed the evolution of eight kidney transplants performed in our
      unit in presence of a positive crossmatch with historical T and/or B lymphocyte
      positive crossmatches. RESULTS: Mean panel reactivity was 76,6 +/- 25,7% (r: 22
      100%), been higher than 75% in six patients. Six patients were recipients of a
      second or third transplant. Immunosuppression consisted of quadruple therapy
      including induction with thymoglobuline. Five patients had delayed graft
      function, and one had primary non-function of the graft. One patient lost her
      graft due to chronic allograft nephropathy in the second year postransplantation.
      Six patients maintained a good renal function (serum creatinine 1,2 +/- 0,5
      mg/dl, proteinuria 0,20 +/- 0,34 g/day). CONCLUSION: Renal transplantation in
      presence of a positive cross-match with historical serum and T lymphocytes and/or
      B lymphocytes, was followed by a satisfactory graft survival.

PMID- 16808266
TI  - [Peritoneal fluid agitation and dialysis dose estimation in automatic peritoneal
      dialysis].

PMID- 16808267
TI  - [Herpes simplex virus encephalitis in a renal transplant patient].
AB  - The incidence of herpes simplex virus (HSV) encephalitis is estimated to occur
      annually in 2-4 cases per million population. HSV encephalitis is exceptional in
      renal transplant patients, we have found two previous reports after an extensive
      bibliography search. We report a case of a 47 years old women renal transplant
      recipient who presented 3 months after transplantation fever, stupor and aphasia.
      The diagnosis HSV encephalitis was achieved by PCR in cerebrospinal fluid and
      magnetic resonance imaging. She was treated with aciclovir for 4 weeks and
      recovered completely without neurologic sequelae.

PMID- 16808268
TI  - [Hypokaliemic nephropathy as a form of presentation of Conn syndrome].
AB  - Hypokalemia is generally associated to neuromuscular symtoms, acid-base disorders
      and even to rhabdomyolysis. However, chronic hypokalemia can induce chronic renal
      failure through a characteristic tubulointerstitial damage consisting on
      vacuolization of epithelial tubular cells and interstitial fibrosis. This entity
      is called hypokalemic nephropathy, quite unusual and probably little know in our
      speciality. We present a clinical report of a patient admitted to our hospital
      with a severe hypokalemia secondary to an aldosterone producing adrenal adenoma
      that was diagnosed during admission. Besides hypokalemia the patient presented
      renal failure. Renal biopsy proved characteristic tubulointerstitial damage as
      described in hypokaliemic nephropathy. In summary, we report a Conn syndrome
      presenting as a hypokalemic nephropathy.

PMID- 16808269
TI  - [Rapid recurrence of ANCA-MPO positive vasculitis after non-heart beating donor
      renal transplantation].
AB  - We report a patient with end stage renal disease with lesions compatibles with
      renal vasculitis antineutrophil cytoplasmic autoantibody (ANCA)-associated in
      phase of sclerosis that underwent renal transplantation from a non-heart beating
      donor after one year of haemodialysis treatment, without evidence of active
      vasculitis. Post-transplantation management was performed according to our
      protocol in this kind of donors with immunosuppressive treatment based on
      daclizumab, half-doses of tacrolimus, mycophenolate mofetil and steroids. In the
      third week the renal biopsy showed an acute necrotizing vasculitis associated
      with crescent glomerulonephritis. The patient was initially diagnosed of acute
      vascular rejection and initiated treatment with 6-metilprednisolone and anti-CD3
      monoclonal anti-bodies. Two days later he developed a cutaneous purpura and the
      skin biopsy showed an acute necrotizing vasculitis. The determination of
      circulating ANCA-anti-myeloperoxidase (MPO) was positive. We initiated treatment
      with oral cyclophosphamide plus mycophenolate mofetil discontinuation with rapid
      improvement of cutaneous lesions and initiation of renal function recovery.

PMID- 16808270
TI  - [Renal polycystic disease of asymmetric onset or unilateral renal cystic
      disease?].

PMID- 16808271
TI  - [UNE-EN ISO 9001-2000 in the public health system].

PMID- 16808272
TI  - [Arterial thrombosis in minimal lesion nephrotic syndrome].

PMID- 16808273
TI  - [Are preventive guidelines for kidney failure observed in patients treated with
      ACEI/ARA II?].

PMID- 16808274
TI  - [Chronic transplant nephropathy].

PMID- 16808275
TI  - [Organ blood flow and microcirculatory vessels in fish].

PMID- 16808276
TI  - [Generation of active oxygen forms by marine invertebrates: mechanisms and
      possible biological functions].

PMID- 16808277
TI  - [Protein phosphatases in the regulation of sodium transport across erythrocyte
      membrane in lamprey, Lampetra fluviatilis].

PMID- 16808278
TI  - [Nucleic acid and protein concentrations in chick embryo organs of different
      age].

PMID- 16808279
TI  - [Phospholipids content in tissues of Microtus oeconomus living in the areas with
      elevated level of radiation].

PMID- 16808280
TI  - [Effect of antibodies to S100 protein on ion channels of incoming and outcoming
      currents in identified neurons of snail, Helix lucorum].

PMID- 16808281
TI  - [Physiological and biochemical aspects of skipped spawning in Barentsev sea cod,
      Gadus morhua].

PMID- 16808282
TI  - [Alteration in activity of protein synthesis system in brain neurons of Citellus
      undulatus at hibernation and hypothermia].

PMID- 16808283
TI  - [Sleep-waking cycle and hypothalamo-hypophysis neurosecretory system of young
      rats at photostimulation].

PMID- 16808284
TI  - [Comparative analysis of functions of reproductive organs in cow and female
      reindeer. Blood cells content in vessels of reproductive organs].

PMID- 16808285
TI  - [Recognition and size comparison of two-dimensional images and three-dimensional
      objects by primitive monkeys].

PMID- 16808286
TI  - [Ability of macaca rhesus to perform elementary mathematical functions].

PMID- 16808287
TI  - [Possible olfactory function of the antennal nerve and the lateral protocerebrum
      of dragonfly (Aeschna grandis) larva].

PMID- 16808288
TI  - [Organization of the hypothalamic region of the diencephalon in sturgeons].

PMID- 16808289
TI  - [Apoptosis and vasopressin, insulin and Bcl-2 expression in neurosecretory system
      of old mice].

PMID- 16808290
TI  - [Changes in nonlinear characteristics of heart rate variability under functional
      load on the cardiovascular system in healthy subjects and coronary heart disease
      patients].

PMID- 16808291
TI  - [Heart rate variability in healthy humans during night sleep].

PMID- 16808292
TI  - [Dependence of the functional capacity of the cardiorespiratory system on the
      body mass in patients with coronary heart disease].

PMID- 16808293
TI  - [EEG spatial organization during intense hyperventilation (cyclic breathing): II.
      EEG correlates of psychovisceral phenomena].

PMID- 16808294
TI  - [The valence use of emotional evaluations of short musical fragments for
      analyzing the functional states of students].

PMID- 16808295
TI  - [Analysis of two components of the human center of mass trajectory in quiet
      standing].

PMID- 16808296
TI  - [Development of the energetics of muscular exercise with age: summary of a 30
      year study: II. "Power zones" and their changes with age].

PMID- 16808297
TI  - [Influence of moderate physical exercise on the cardiac rhythm parameters of
      elementary and junior high school children].

PMID- 16808298
TI  - [Individual characteristics of external respiration during intermittent
      normobaric hypoxia].

PMID- 16808299
TI  - [Regional characteristics of external respiration under the environmental
      conditions of Northeastern Russia].

PMID- 16808300
TI  - [Functional variability of the indices of ventilation and gas exchange in healthy
      young men in Western Siberia].

PMID- 16808301
TI  - [Airway conductance in high school students living in the European North].

PMID- 16808302
TI  - [Characteristics of the formation of compensatory and adaptive responses of
      sailors to chronic stress].

PMID- 16808303
TI  - [Physiological and ethnogenetic risk factors for cardiovascular thrombosis].

PMID- 16808304
TI  - [The role of monocytes in the effects of beta-endorphin and selective agonists of
      mu- and delta-Opiate receptors on the proliferative activity of peripheral blood
      lymphocytes].

PMID- 16808305
TI  - [Endotoxin aggression in the pathogenesis of chronic inflammatory diseases of
      small pelvis organs and infertility, or an antiendotoxin approach to their
      treatment].

PMID- 16808306
TI  - [Immunophysiology of endothelial cells].

PMID- 16808307
TI  - [Reactions of the autonomic nervous system of students with different
      characteristics of higher nervous activity in the situation of examination
      stress].

PMID- 16808308
TI  - [Sphygmographic method for determining the vasoconstrictor sensitivity of the
      circulatory apparatus to hypercapnia in athletes].

PMID- 16808309
TI  - [Disturbance in oscillatory and rotational movements in living systems in the
      infrared range as a vital activity factor whose changes result in molecular
      pathology].

PMID- 16808310
TI  - [Influence of recombinant human erythropoietin (rHuEPO) on plasma levels of
      selected hormones in females with rheumatoid arthritis].
AB  - During recent years, it was shown, that treatment with recombinant human
      erythropoietin (rHuEPO) stimulates erythropoiesis in patients both with renal and
      nonrenal anaemia. Additionally in patients with chronic renal failure treated
      with rHuEPO a significant, however only transient, influence on function of
      endocrine glands was also found. The present study aimed to asses for the first
      time the influence of rHuEPO on function of endocrine organs in anaemic patients
      with rheumatoid arthritis and normal renal function. Twenty two woman with
      rheumatoid arthritis and concomitant anaemia (Ht < or = 30%) were enrolled into
      the study. In 13 of them rHuEPO was used during 4 months (5000 IU 2 times per
      week s.c.). The rest 9 woman with similar degree of anaemia did not receive
      rHuEPO therapy. In woman of both groups intensive clinical and biochemical
      monitoring during 4 months period was performed. Blood samples were withdrawn
      before and after 4 months of rHuEPO therapy or clinical observation only. In
      these blood samples plasma concentrations of somatotropin (HGH), insulin (IRI),
      aldosterone (ALD), atrial natriuretic peptide (ANP), 25-hydroxycholecalciferol
      (25OHD3), intact parathyroid hormone (iPTH) and plasma renin activity (PRA) were
      estimated. After 4 months of rHuEPO therapy significant increase of plasma IRI,
      ANP concentrations and significant decrease of PRA and plasma ALD, HGH
      concentrations were found. Therapy with rHuEPO does not influence significantly
      plasma iPTH and 25OHD3 concentration. During 4 months of clinical observation in
      patients not treated with rHuEPO, plasma concentrations of HGH, IRI, ALD, ANP,
      25OHD3, iPTH and plasma renin activity (PRA) did not change significantly.
      Results obtained in this study suggest, that rHuEPO therapy does influence the
      function of endocrine organs also in patients with rheumatoid arthritis with
      normal renal function.

PMID- 16808311
TI  - [Quantitative assessment of mRNA TGF-beta1 in liver tissue in connection with
      serum mean daily level of TGF-1 in chronic hepatitis B patient].
AB  - Monitoring of fibrosis process with the use of histopathologic studies on liver's
      bioptates is limited, so it is attempted to find reliable, obtained with less
      invasive methods, sensitive and reflecting fibrosis dynamics markers of this
      process. The aim of the study was simultaneously to assess liver's expression as
      well as circadian and mean daily TGF-betal concentration in serum of patients
      with chronic hepatitis type B in comparison to control group. Studies were
      performed on 50 patients (9 women, 41 men) aged 45.9 +/- 2.3 years with chronic
      hepatitis type B. Control group consisted of 20 patients (mean age 38.6 +/- 3.7
      years), in which so called minimal changes without fibrosis were observed in
      histophatologic bioptate of liver. Blood for studies was collected every 4 houres
      during the day. Serum concentration of TGF-betal was assessed with the use of
      ELISA method, and expression of mRNA TGF-betal in liver with QRT-PCR method. No
      significant difference between circadian as well as mean daily serum TGF-betal
      concentration beetwen control group and the group with chronic hepatitis type B
      was shown. Increased expression of mRNA, TGF-betal in bioptate of liver of
      patients with chronic hepatitis type B in comparison to control group was noted.
      In "minimal changes" control group presence of significant positive correlation
      between expression of mRNA TGF-beta1 in liver and concentration of this cytokine
      in serum was shown, in the group of patients with chronic hepatitis B this
      connection was not noted.

PMID- 16808312
TI  - [The effect of hypolipemic therapy with diet and simvastatin on the course of
      angina pectoris and the results of exercise stress test in patients with coronary
      artery disease].
AB  - Statins are the multi-directorial acting drugs in atherosclerosis prevention,
      which decrease the overall and cardiovascular mortality. The aim of this study
      was to estimate the effect of six-month long hypolipemic therapy with diet and 20
      mg of simvastatin on clinical intensity of angina pectoris and the course of
      exercise stress test. PATIENTS AND METHODS: We studied 44 patients with typical
      anginal chest pain. In all blood sampling and treadmill stress test were made,
      and next in all hypolipemic diet and simvastatin 20 mg were recommended. After
      four weeks and six months of treatment clinical assessment and exercise test were
      made. RESULTS: After four weeks and six month long observation period the
      decrease of total and LDL cholesterol, triglycerides and fibrinogen were found.
      Moreover, we have observed the improvement in frequency of anginal symptoms,
      their intensity in CCS classification and number of nitroglycerin tablets taken
      per week. The course of exercise test was also ameliorated: the percentage of
      patients, in whom stress test was finished because of chest pain was decreased,
      time of chest pain duration after exercise cessation was shorter, the percentage
      of patients with significant ST interval depression diminished, maximal ST
      interval depression as well as the time of significant ST interval depression
      duration also decreased. Although improvement in values of mentioned parameters,
      after six months long therapy with simvastatin the percentage of patients with
      Duke's treadmill score value showing intermediate cardiovascular risk (between 
      10 and +4) increased. In conclusion, therapy with hypolipemic diet and
      simvastatin already after four weeks decreased plasma lipids and fibrinogen
      levels and improved the course of angina pectoris and exercise stress test, what
      suggested its effectiveness not only as the treatment improving atherosclerosis
      risk factors, but also with prompt and clinical important effect ameliorating the
      handicapped coronary reserve.

PMID- 16808313
TI  - [Comparison of the effect of nitroglycerine and pentaerithritol compositum on
      exercise time restricted by anginal pain or objective parameters of ischaemia in
      patients with stable angina].
AB  - Short acting nitrates are commonly used to prevent the anginal pain. The purpose
      of the study was to compare antianginal efficacy of Pentaerythritol compositum
      (20 mg of pentaerythritol tetranitrate and 0.5 mg of nitroglicerine) and 0,5 mg
      of nitroglycerine. Twenty patients aged 45-75 years with stable angina were
      enrolled. Antianginal effectiveness was evaluated during treadmill test. Time to
      ischemic pain and/or electrocardiographic parameters of ischemia were measured.
      It was found that Pentaerythritol compositum was superior to nitroglycerine in
      preventing angina with the difference disappearing 60 minutes after drug
      administration. Both drugs were well tolerated. Achieved results show that
      Pentaerythritol compositum can be effective as antianginal drug in patients with
      stable angina.

PMID- 16808314
TI  - [The use of AF SUPRESSION pacing algorithm in supression of paroxysmal atrial
      fibrillation in patients with bradycardia--one center experience].
AB  - Heart pacing with algorithms preventing episodes of paroxysmal atrial
      fibrillation (PAF) is one of the modern methods of PAF treatment. The usefulness
      of AF suppression TM pacing algorithm in Integrity AFx DR pacing was evaluated.
      The study group consisted of 7 patients with paroxysmal AF (for average 2,5 year;
      requiring on average 6 cardioversions in ICCU per year) and standard pacemaker
      indications. The small number of enrolled patients resulted from high cost of the
      pacemaker. In our study we turned on AF suppression TM pacing algorithm 3 months
      after pacemaker implantation and evaluated the number of PAF episodes at 3 and 6
      months. Pharmacotherapy was not changed. Antiarrhythmic stimulation resulted in
      reduction of the number of PAF (on average by 11) at 3 months and was well
      tolerated by the patients. AF Suppression(tm) pacing algorithm is effective only
      if PAF is preceded by supraventricular extrasystole.

PMID- 16808315
TI  - [Transient hyponatremia the first symptome of multiple endocrine neoplasia type 1
      (MEN 1)--case report].
AB  - Transient character of laboratory abnormalities is usually explained as a false
      result of estimation. Spontaneous disappearance of laboratory abnormalities could
      be recognized as non-important and contradicting serious disease. Presented case
      of multiple endocrine neoplasia type 1 (MEN 1) denies these assumptions. Sixty
      nine-years old woma was admitted to the internal department because of weakness,
      fever, dehydration and hypotension--symptom accompanying an upper respiratory
      infection. Moderate hyponatremia (122.6 mmol/l) was found in a routine laborator
      examination. All clinical symptoms as well as hyponatremia disappeared during
      hospitalization. Transient hyponatremi was not ignored. Further laboratory and
      hormonal investigations were performed. Fasting, morning serum cortisol
      concentration and 24-hours urinary excretion of free corticosterids were
      decreased and Synacten stimulation test reveale incomplete cortisol stimulation.
      Pituitary tumour was found in the CT scan. Moreover blood ionized calcium an
      parathyroid hormone were elevated. These results revealed secondary adrenal
      insufficiency, non-functioning pituitary tumor and hyperparathyroidism. Removal
      of pituitary adenoma was done. Asymptomatic hypercalcemia persists. Presented MEN
      1 was atypical because: 1. Usually hyperparathyroidism is the first and most
      frequent symptom while in our patient the first symptom was transient
      hyponatremia secondary to the pituitary tumor, 2. was diagnosed in the old age
      while the majority of MEN 1 patients are younger, 3. asymptomatic course of
      hypercalcemia indicates that in some of elder patients removal of the parathyroid
      glands might not be necessary.

PMID- 16808316
TI  - [Recurrent hemoptysis following thienopyridines and amiodarone administration.
      therapeutic dilemma].
AB  - The authors describe a case of a 74-year-old man with advanced coronary heart
      disease in whom pulmonary hemorrhagic complications during therapy with
      ticlopidine and subsequently with clopidogrel and amiodarone were observed. Fever
      and massive hemoptysis following five days of ticlopidine treatment, before
      elective coronary angiography, were noticed. Transient interstitial X-ray changes
      of the right lung were visible. Three months later a new episode on the third day
      of clopidogrel administration was manifested. He was after PCI, performed because
      of ACS complicated with ventricular fibrillation. Two days following clopidogrel
      discontinuation hemoptysis remitted but after ten days occurred again (this time
      with bilateral X-ray changes). Amiodarone, given after VF, was stopped.
      Spectacular improvement with steroid treatment was observed. Indobufen
      (reversible COX- 1 inhibitor) as an antiplatelet therapy was availed. The authors
      discuss therapeutic dilemma concerning the patient with coexisting different
      diseases.

PMID- 16808317
TI  - [Caplan's syndrome: case report].
AB  - A case of a 56-years old male with rheumatoid arthritis and unclear tumoral
      radiological changes in the lungs was described. Since noninvasive diagnostic
      procedures failed to explain nature of the pulmonary changes, an open pulmonary
      biopsy was performed. Pathological examination revealed presence of rheumatoid
      nodules and pneumoconiosis, typical for Caplan's syndrome. In the past, the
      patient had been working in foundry industry for 16 years and he had been exposed
      to silica and iron dust. Articular symptoms were revealed prior to finding the
      lung changes even dust exposure had occurred many years earlier. In spite of the
      fact that rheumatoid arthritis is a relatively common disease and pneumoconiosis
      is also not rare entity, the coexistence of both conditions i.e. Caplan's
      syndrome has been rarely diagnosed and described.

PMID- 16808318
TI  - [Cardiovascular events in patients with systemic lupus erythematosus and
      rheumatoid arthrosis. New view on the old problem].

PMID- 16808319
TI  - [The role of tissue factor pathway inhibitor (TFPI) in thrombotic complications].

PMID- 16808320
TI  - [Usefulness of tumour markers in the diagnostic of gastric cancer].

PMID- 16808321
TI  - [Music application in the therapy of psychic and somatic diseases].

PMID- 16808322
TI  - [Hepatorenal syndrome].

PMID- 16808323
TI  - [Effect of grapefruit juice on bioavailability of drugs].

PMID- 16808324
TI  - The role of viral and cellular proteins in the budding of human immunodeficiency
      virus.
AB  - For over two decades, research on Human immunodeficiency virus (HIV), which is
      responsible for AIDS, has aimed at understanding of the molecular mechanisms used
      by this virus during its life cycle. An essential step in the HIV life cycle is
      the budding, which promotes the release of viral particles from the host cell. It
      has recently been revealed that HIV in the process of budding uses besides one
      viral protein also the machinery of the infected cell, in particular the proteins
      Tsg101 and ubiquitin. The viral protein is the p6 domain of the Gag precursor
      polyprotein. In normal cells, Tsg101 functions as a regulator of endocytic
      trafficking that recognizes ubiquitinated cargo and directs its delivery to
      degradative compartments. In HIV-infected cells, Tsg101 and ubiquitin interact
      with Gag p6 to promote the release of new viral particles from the host cell.
      Molecular mechanisms underlying the process of HIV budding from infected cells
      suggests a whole new range of drug targets that could prove useful in AIDS
      suppression in HIV-positive patients.

PMID- 16808325
TI  - A DNA vaccine that encodes rabies virus glycoprotein lacking transmembrane domain
      enhances antibody response but not protection.
AB  - Rabies virus (RV) glycoprotein (gp) consists of three domains: cytoplasmic,
      transmembrane and ectodomain. It occurs in a complete, membrane-bound form within
      the infected cell, but it is released from them in a deleted, secreted form
      lacking the transmembrane domain. This study was performed to test the importance
      of the transmembrane domain for the capability of the RV gp gene, introduced into
      mice via a recombinant plasmid (DNA vaccine), to induce immune response and
      protection against challenge. Although the antibody response to the secreted form
      of gp was higher than that to complete gp, the protective efficacy of the
      respective DNA vaccine against challenge was not better than that of the DNA
      vaccine inducing complete gp. This indicates that the transmembrane domain of RV
      gp is important for generating protection against rabies and should be present in
      RV DNA vaccines.

PMID- 16808326
TI  - Induction of tumor necrosis factor alpha in murine macrophages with various
      strains of Coxiella burnetii and their lipopolysaccharides.
AB  - The ability of various strains of Coxiella burnetii (C.b.) and their phase I and
      II lipopolysaccharides (LPSs) to induce tumor necrosis factor alpha (TNF-alpha)
      in peritoneal Balb/c mouse macrophages in vitro was investigated. Considerable
      differences in the induction ability were observed in dependence on the strain
      applied. In a TNF-alpha bioassay, the most effective inducers were both
      corpuscles and LPSs of the strains Priscilla and Scurry, followed by Nine Mile,
      Luga, and Henzerling I. In contrast, in ELISA, the most effective inducers were
      LPSs of the strains Luga and Henzerling, followed by Nine Mile, Priscilla, and
      Scurry. The role of toll-like receptor 4 (TLR4) in the induction was confirmed by
      the use of C3H/HeJ mouse macrophages. Thus, the induction of TNF-alpha was much
      higher in Balb/c mouse macrophages than that in TLR4-deficient C3H/HeJ mouse
      macrophages. Differences in the results of the bioassay and those of ELISA
      suggest a role of another secreted factor(s) induced with C.b. in murine
      macrophages that could act synergically with TNF-alpha in L929 cells in the
      bioassay. The observed differences in TNF-alpha induction might play a role in
      the pathobiology of Q fever.

PMID- 16808327
TI  - Development of a real-time PCR for Tomato yellow leaf curl Sardinia virus.
AB  - Recently, tomato yellow leaf curl disease has become important for the tomato
      grown both in greenhouse and field conditions in Tunisia. Here, we describe a
      rapid, specific, reliable, and sensitive real-time PCR, based on TaqMan
      chemistry, for Tomato yellow leaf curl Sardinia virus (TYLCSV). This method
      proved suitable for the detection and quantification of this virus in tomato,
      pepper and bean plants. It detected the virus even in the samples that were
      negative by conventional assays.

PMID- 16808328
TI  - Molecular variability of the coat protein gene of Potato virus Y from tobacco in
      China.
AB  - Thirty-three tobacco samples showing typical symptoms of Potato virus Y (PVY)
      infection were obtained from tobacco fields in various regions of China. The
      results of indirect ELISA confirmed the infection with PVY. All the isolates had
      a capacity to infect tobacco systemically in greenhouse, causing either of two
      main symptoms: veinal necrosis and mosaic. The nucleotide and amino acid
      sequences of the coat protein (CP) gene and protein, respectively, of the
      isolates were determined. Comparison of the isolates revealed a high conservation
      of the CP gene with an identity of 83.2%. A phylogenetic tree of 41 Chinese
      isolates of PVY, based on complete CP gene, showed 3 groups corresponding to the
      strains PVYNTN (A group), PVYO (C group) and a putative new strain similar to
      PVYN (B group). The amino acid sequences of complete CP protein of the isolates
      showed an identity of 87.6%. The highest identity was observed in the C-terminal
      half of the CP protein, where only 11 amino acid differences could be observed,
      in contrast to the N-terminal half with 22 differences.

PMID- 16808329
TI  - Nucleotide sequence analysis of the ORF0 region of Potato leafroll virus isolates
      from Tunisia.
AB  - Potato leafroll virus (PLRV) isolates from potato plants from different regions
      of Tunisia were investigated for the ORF0 variable region of genomic RNA using
      PCR, nucleotide sequencing and sequence analysis. Based on the ORF0 variable
      region nucleotide sequence, individual Tunisian isolates were more homologous as
      a group compared to the isolates originating from other parts of the world. There
      was no correlation between bioclimatic origin of the isolates and their ORF0
      sequence. Alignment of the deduced amino acid sequences showed that the P0
      protein was not much conserved. Unexpectedly, Tunisian isolates were found to be
      most homologous to Peruvian ones both at nucleotide and amino acid level. A
      phylogenetic tree, based on the P0 amino acid sequence, showed that all the PLRV
      isolates were located in two major clusters regardless of their geographic
      origin. In the second cluster, three sub-clusters could be distinguished. These
      results provide valuable information for molecular characterization of the PLRV
      isolates occurring in Tunisia.

PMID- 16808330
TI  - JC polyomavirus reactivation is not associated with herpes zoster.
AB  - Herpes zoster (HZ) is a neurocutaneous disease caused by Varicella-zoster virus
      (VZV) as a consequence of declined cell-mediated immunity, immune suppression and
      immunodeficiency. As reactivation of JC polyomavirus (JCPyV) might be linked with
      immunodeficiency or immunosuppressive therapy, the relationship between HZ and
      JCPyV reactivation was investigated. The incidence of JCPyV in urine samples from
      102 patients with HZ and 100 healthy individuals from South Korea was determined
      by PCR. The incidence values for HZ patients and control individuals did not
      differ significantly (24.5% vs. 20.0%, respectively, P = 0.5391). When different
      age groups were monitored, the positivity values of 21.1%, 20.0%, and 30% were
      found for 20-39, 40-59 and over 60 year-old patients, respectively. In order to
      determine the genotype of JCPyV isolates, their VP1-large T antigen (VT)
      intergenic region was PCR amplified, sequenced and analyzed. Three distinct
      types, namely 1, 2A and 7B were found in 8%, 24%, and 68% of were found among 25
      isolates from HZ patients. Using phylogenetic analysis, the type 1 isolates were
      assigned to the 1C subtype. These results indicate that HZ does not play an
      important role in JCPyV reactivation and is not associated with JCPyV.

PMID- 16808331
TI  - Development and evaluation of a multiplex RT-PCR for detecting main viruses and a
      viroid of potato.
AB  - A multiplex RT-PCR (mRT-PCR) for detecting four potato viruses (Potato virus S
      (PVS), Potato virus X (PVX), Potato virus Y (PVY), and Potato leaf roll virus
      (PLRV)) and one potato viroid (Potato spindle tuber viroid (PSTVd)) was
      developed. The mRT-PCR consisted of one reaction with specific primers designed
      according to the sequences of coat protein (CP) genes of respective viruses and
      the sequence of the viroid. The entire procedure from tissue grinding to RT-PCR
      results takes about 4 hrs. The reliability of the method was tested on leaves
      sampled from the field, greenhouse and in vitro-grown plants by comparison with
      double-antibody sandwich ELISA (DAS-ELISA). A high correlation between these two
      methods was observed. The mRT-PCR was also evaluated by testing infected samples
      obtained from the International Potato Center, Lima, Peru; this testing confirmed
      its high reliability and sensitivity.

PMID- 16808332
TI  - Detection of transgene copy number by analysis of the T1 generation of tobacco
      plants with introduced P3 gene of potato virus A.
AB  - Real-time PCR, namely the deltadeltaCt method was used to determine the relative
      copy number of Potato virus A (PVA) P3 gene in the genome of the T1 generation of
      18 transgenic tobacco lines. These results were compared with segregation ratios
      of kanamycin (Km)-resistant phenotype in T1 plants of each line and were found to
      be, in general, concordant. All the five lines with the Mendelian segregation
      ratio of 3:1 carried one gene copy. In 12 of 13 lines with uneven segregation
      more inserted gene copies were detected. Only for one line the real-time PCR and
      phenotype segregation differed. According to our results the real-time PCR of T1
      generation may be used as supplementary method of estimation of the number of
      transgene copies in the case of nonavailability of the original T0 plants.

PMID- 16808333
TI  - Assessment of efficacy of a live oral poliovirus vaccine for virulent Sabin-like
      poliovirus 1 strains in Japan.
AB  - Virulent Sabin-like poliovirus (VSLP) was isolated from river and sewage waters
      between October 1993 and September 1995 in Toyama Prefecture, Japan (Yoshida et
      al., Lancet 356, 1461-1463, 2000). In this study, to assess the possibility of an
      epidemic of poliomyelitis caused by a VSLP in Japan under the current vaccination
      policy of administration of live attenuated oral poliovirus vaccine (OPV), we
      determined titers of serum neutralizing antibodies to poliovirus 1 (PV-1) strains
      Sabin (vaccine strain), Mahoney (wild-type strain) and G4-12 (VSLP) in various
      groups of residents of Toyama Prefecture, Japan. The seropositivity and geometric
      mean neutralizing antibody titers against these strains in the individuals who
      obtained two doses of OPV were 99.1%, 94.5% and 95.5%, respectively, and 564, 186
      and 194, respectively. Although the antibody titers to G4-12 were lower compared
      with those to Sabin, these results indicate that the OPV vaccination policy in
      Japan has been effective in preventing poliomyelitis caused by VSLPs. These
      results also suggest that (i) an epidemic of poliomyelitis caused by a VSLP has
      not occurred in Japan due to herd immunity, and (ii) the possibility of
      reemergence of VSLPs will be prevented if sufficient herd immunity is acquired
      immediately after completion of the OPV vaccination in accordance with the
      poliomyelitis eradication program.

PMID- 16808334
TI  - Changes in the reactivity of the immune system of children after the influenza A
      infection.

PMID- 16808335
TI  - [Computer simulation of the association of caffeine and actinocin derivatives in
      aqueous solutions].
AB  - The association of caffeine and actinocin derivatives (ActII), the analogues of
      anticancer antibiotic actinomycin D, was studied by molecular dynamics
      simulation. The simulation was carried out with consideration of solvent
      molecules, water and Na+ and Cl- ions. The information was obtained which
      describes in detail the association of caffeine and ActII in water and aqueous
      salt solutions and interaction of monomers and dimers with water-ion environment.
      The hydration schemes for monomers and associated forms of caffeine and ActII
      were determined. The calculated values of interaction energies of monomers in
      dimers show that the aggregation of these compounds in aqueous solutions is an
      energetically favorable process. The self- and heteroassociates were stabilized
      by van-der-Waals, electrostatic, and hydrophobic interactions and also due to the
      formation of intermolecular hydrogen bonds. The reconstruction of hydration
      shells of monomers after their association in water is energetically unfavorable
      and destabilizes the dimer formation. The reconfiguration of hydration shell of
      monomers after their association in the presence of Na+ and Cl- ions is
      energetically favorable for dimer of singly charged ActII+ and heteroassociates
      Cf-ActII+. The formation of heterodimers Cf-ActII is energetically more favorable
      than the formation of self-associates of caffeine. Therefore, caffeine can
      decrease the concentration of aromatic biologically active compounds, actinocin
      derivatives, in solution through the formation of heteroassociates and hence lead
      to a decrease in the pharmacological activity of the analogues of anticancer
      antibiotic acting as an interceptor.

PMID- 16808336
TI  - [Estimation of the hydrophobic effect based on the density functional theory].
AB  - Using the fundamental measure treatment of the density functional theory, we have
      developed a method to calculate the solvation of hydrophobic solutes. The method
      allows one to calculate the density profile and the solvation energy for
      hydrophobic molecules. An additional benefit of the method is the possibility to
      calculate interaction forces and the mean force potential between hydrophobic
      nanoparticles. On the basis of the method, the solvation energies for spherical
      solutes of different sizes from one angstrom up to several nanometers were
      calculated.

PMID- 16808337
TI  - [Effect of temperature on the modification of spectral properties of tryptophan
      aqueous solutions induced by water previously treated with laser radiation].
AB  - It was shown that preliminary exposure of a solvent (water) to low-intensity
      laser radiation reduces the tryptophan fluorescence intensity, and this
      fluorescence quenching effect is retained throughout the temperature range
      explored (from 8 up to 50 degrees C). The effects found are interpreted as
      resulting from changes in solvent properties induced by the action of
      electromagnetic radiation on interaction of water molecules with solute.

PMID- 16808338
TI  - [Intramolecular dynamics of human erythrocyte membrane proteins upon modification
      of spectrin by tryptophan phosphorescence].
AB  - The slow (millisecond) protein internal dynamics of isolated human erythrocyte
      membranes in suspension without treatment, after deleting 95% of spectrin, after
      spectrin thermal denaturation upon acidification of medium in the pH range 6.0
      4.0, and spectrin extracted in solution from membranes has been studied by room
      temperature tryptophan phosphorescence. It has been established that integral
      proteins and spectrin differ in structural and dynamic state. Millisecond
      movements of structural elements of integral proteins are more restricted
      compared with those of spectrin. The removal of spectrin from the membrane led to
      an increase in slow fluctuations of integral protein structure. This indicates
      that spectrin participates in the control of the structural and dynamic state of
      erythrocyte membrane proteins. As medium was acidified in the pH range 6.0-4.0,
      the protein slow internal dynamics of membranes in native state decreased, which
      was explained by spectrin pH aggregation. After thermal denaturation of spectrin,
      no pH-induced increase of membrane protein structure rigidity was observed.

PMID- 16808339
TI  - [Effect of temperature on intramolecular dynamics and conformational state of
      bacterial alkaline phosphatase].
AB  - The slow internal dynamics and the conformational state of Escherichia coli
      alkaline phosphatase by the action of temperature in the range 0-100 degrees C
      have been investigated by tryptophan room temperature phosphorescence and
      fluorescence. It has been shown that heating an alkaline phosphatase solution in
      the interval 0-70 degrees C leads to a substantial increase in the slow internal
      dynamics. A further increase in temperature to 95 degrees C causes a reversible
      enhancement of internal dynamics and a partial unfolding of the globule. Heating
      the protein solution in a narrow temperature range 97-100 degrees C induces an
      irreversible conformational transition, which is characterized by total unfolding
      of the globule, a drastic increase in internal dynamics, and the loss of
      enzymatic activity.

PMID- 16808340
TI  - [Kinetics of ligand binding to nucleic acids at random fillings].
AB  - Ligand binding with nucleic acids is described in frames of the theory of random
      processes. It is shown that the probabilistic description of binding of a ligand
      to nucleic acid allows one to describe not only the kinetics of changes in the
      number of bound ligands at arbitrary fillings but also to calculate stationary
      values of the number of bound ligands and its dispersion. A general analysis of
      absorption isotherms and the kinetics of ligand binding with nucleic acids allows
      one to determine the rate constants of formation and decomposition of the ligand
      nucleic acid complex. A comparison of the results obtained with the case of low
      fillings is conducted.

PMID- 16808341
TI  - [Physico-chemical properties and thermostability of human hemoglobin molecules
      modified by rheopolyglucin and dialdehydedextrane].
AB  - The structural characteristics and thermostability of human hemoglobin molecules
      modified by rheopolyglucin and dialdehydedextrane have been studied. The
      influence of mixture pH, the exposure time, and temperature of incubation and the
      rate of dextrane oxidation on the intensity of conjugation of human hemoglobin
      with dialdehydedextrane has been estimated. Optimal conditions for the binding of
      hemoglobin to dialdehydedextrane have been determined. The formation of the
      hemoglobin- dialdehydedextrane complex leads to the shielding of protein
      chromophore groups by the polysaccharide matrix and the transformation of a part
      of hemoproteid molecules from the low-spin form (HbO2) to high-spin forms (Hb,
      MetHb). It has been found that the temperature of denaturation transition for the
      native protein and hemoglobin in the presence of rheopolyglucin is 60 degrees C,
      and that for the hemoglobin-dialdehydedextrane conjugate is 80 degrees C. The
      latter is probably determined by the enhancement of hydrophobic interactions
      inside the protein globule under the effect of dialdehydedextrane and by the
      ability of the externally-bound carbohydrate components to prevent the
      association of hemoglobin molecules.

PMID- 16808342
TI  - [Investigation of ribosomes of E. coli and T. maritima by atomic force
      microscopy].
AB  - Subunits 70S, 50S, and 30S of ribosomes of E. coli and T. maritima have been
      studied by atomic force microscopy. A considerable heterogeneity of structures
      was visualized when 70S and 30S subunits were sorbed on mica. The linear size and
      the height of molecules were estimated. It was found that the heights of
      ribosomes of E. coli and T. maritima substantially differ. The average height of
      70S ribosomes of E. coli was 9.4 + 0.01 nm and that of T. maritima was 10.35 +/-
      0.02 nm. The differences in the dimensions were probably determined by special
      organization of the mobile ribosomal element the L7/L12-stalk.

PMID- 16808343
TI  - [Photochemical properties of a bacteriorhodopsin analogue containing 13-desmethyl
      13-(trifluoromethyl)retinal].
AB  - It was shown that the substitution of the CF3 group in the structure of retinal
      for the methyl group in the position C-13 causes not only a decrease in the
      affinity of the proton to the nitrogen atom in the Schiff base (pK approximately
      8.4) but also considerably changes the photochemical properties of the
      bacteriorhodopsin analogue. At pH > 6.5, the rate of the Schiff base
      reprotonation during M decay depends on the concentration of protons in medium.
      In the photocycle of the "yellow" M-like form with the deprotonated Schiff base,
      the long-wavelenght product absorbing at 625 nm is formed, which has a similar pH
      dependence of decay kinetics. Both processes had also similar activation energies
      (about 15 +/- 1 kCal/mol). The conclusion was made that, in both cases, a proton
      transfer from water medium through the donor part of the channel accordingly up
      to the Schiff base and Asp96 takes place. In this analogue, however, the
      structure of water molecules necessary for the stabilization of the proton on the
      Schiff base is broken. As a result, the dehydration of the preparation gives rise
      to a fraction of M-like form of bacteriorhodopsin with the deprotonated Schiff
      base.

PMID- 16808344
TI  - [Visualizing single fluorophores in live cells].
AB  - The methods have been described that can be used to visualize single fluorescent
      molecules in live cells: laser epifluorescent, confocal, near-field, two-photon,
      and total internal reflection microscopy. Each method has its own advantages and
      limitations. We showed that total internal reflection microscopy is a method of
      choice for single fluorophore visualisation near substrate-medium interface. It
      can be used to study receptors, ion channels, and many cytoskeleton or signalling
      molecules located at or in close proximity to basal cell membrane. It was shown
      that it is very important to use rigorous criteria for single fluorophore
      identification since these objects emit a limited number of photons before
      irreversible photo-bleaching, and their fluorescence is often obscured by cell
      auto-fluorescence and out-of-focus fluorescence. Methods used for lateral
      mobility studies of single molecules floating on cell membrane were also
      described.

PMID- 16808345
TI  - [Energy transformation coupled to formate oxidation during anaerobic
      fermentation].
AB  - A correlation between the rate of ATP synthesis by F0F1 ATP-synthase and formate
      oxidation by formate hydrogen lyase (FHL) has been established in inverted
      membrane vesicles of Escherichia coli JW 136 mutant with double deletions (delta
      hya/ delta hyb) of hydrogenase 1 and 2 grown anaerobically on glucose in the
      absence of external electron acceptors (pH 6.5). ATP synthesis was suppressed by
      H+ -ATPase inhibitors N,N'-dicyclohexylcarbodiimide (DCCD) and sodium azide as
      well as by the protonophore carbonyl cyanide-m-chlorophenyhydrazone (CCCP).
      Copper ions inhibited formate-dependent hydrogenase and ATP-synthase activities
      but did not affect the ATPase activity of vesicles. The maximal rate of ATP
      synthesis (0.83 microM/min x mg protein) stimulated by K+ ions was determined
      when sodium formate, ADP and inorganic phosphate were applied simultaneously. The
      results confirm the assumption about the dual role of hydrogenase 3, formate
      hydrogen lyase subunit, which is able to couple the reduction of protons to H2
      and their translocation through a membrane with chemiosmotic synthesis of ATP.

PMID- 16808347
TI  - [Production of oxygen free radicals by cardiac mitochondria: effect of hypoxia
      reoxygenation].
AB  - The effect of the duration of hypoxia on superoxide radical production in
      isolated rat heart mitochondria was studied by the spin trapping technique. 4,5
      Dioxybenzene was used as a spin trap. Samples were placed into the cavity of an
      EPR spectrometer in thin-wall gas-permeable capillary tubes, which allowed
      keeping the suspension of mitochondria in aerobic or hypoxic conditions.
      Previously we have demonstrated that the rate of superoxide generation by
      mitochondria isolated from postischemic hearts depends radically on the duration
      of myocardial ischemia. By contrast, in mitochondria isolated from intact hearts,
      the effect did not depend on the duration of hypoxia. The rate of superoxide
      production by isolated mitochondria in the presence of antimycin A (a complex III
      Q-cycle inhibitor) and complex I or complex II substrates was 0.9 +/- 0.1 nmole
      O2*- /min/mg protein at 25 degrees C. Under reoxygenation conditions, after 10
      min of hypoxia, the rate of superoxide production was considerably higher than
      before hypoxia. At the same time, after prolonged hypoxia, its value was
      practically the same as after 10-min hypoxia. The results enable the conclusion
      that isolated mitochondria are less sensitive to hypoxic conditions than
      mitochondria in ischemic heart.

PMID- 16808346
TI  - [Interaction between dinitrosyl iron complexes and intermediate products of
      oxidative stress].
AB  - The interaction between glutathione-containing dinitrosyl iron complexes and
      superoxide radicals has been studied under the conditions of superoxide radical
      generation in mitochondria and in a model system xanthine-xanthine oxidase. It
      has been shown that both superoxide radical and hydroxyl radical are involved in
      the destruction of dinitrosyl iron complexes. At the same time, iron contained in
      dinitrosyl iron complex, apparently, does not catalyze the decomposition of
      hydrogen peroxide with the formation of hydroxyl radical. It has been found that
      dinitrosyl iron complexes with different anion ligands inhibit effectively the
      formation of phenoxyl probucol radical in a hemin-H2O2 a system. In this process,
      different components of the dinitrosyl iron complexes take part in the
      antioxidant action of these complexes.

PMID- 16808348
TI  - [Changes in the free-radical state and level of free iron during the formation of
      drug resistance in tumor cells].
AB  - The development of resistance of K562 human erythroleukemia cells to doxorubicin,
      a widely used antitumor antibiotic with the prooxidant action, leads to changes
      in the free-radical state of cells. It has been found that the formation of
      superoxide anion in resistant cells decreases. The introduction of doxorubicin to
      the culture medium induced a considerably lesser increase in the formation of O2*
      in resistant cells compared to sensitive cells. At the same time, a strong
      decrease in the ESR signal of semiquinone type with a g-factor of 2.006 was
      observed in a culture of resistant cells grown in the absence of doxorubicin as
      compared with sensitive cells grown under similar conditions. At the same time, a
      decrease in the level of paramagnetic nitrosyl complexes of nonheme iron in
      resistant cells was recorded, indicating a decrease in the content of free
      nonheme iron as a result of the formation of drug resistance. In addition, a
      decrease in the level of mRNA of the transferrin receptor in resistant cells was
      found by the RT-PCR. These data indicate the development of a coodinated redox
      dependent adaptive response, which makes itself evident as a suppression of free
      radical processes during the formation of resistance of K562 cells to
      doxorubicin.

PMID- 16808349
TI  - [Effect of hydrophobicity of yeast cell envelope on the rate of autooxidation of
      methyloleate].
AB  - The relationships between the antioxidant and antiperoxide properties and the
      lipid composition of yeast cell envelope prior to, and after the reaction with a
      liquid culture medium were studied. Correlations between the hydrophobicity of
      envelopes, their lipid composition and the parameters of the kinetic curves of
      the oxidation of model methyloleate in the presence of lipids were established.
      It was found that, irrespective of the general content of lipids in yeast cell
      envelope, preparations with high antiperoxide activity of lipids had a high
      hydrophobicity and sorbed lipophilic prooxidants from medium, whereas
      preparations with low antiperoxide activity were less hydrophobic and adsorbed
      predominantly lipophilic inhibitors. It was found that the most comprehensive
      information on the physicochemical properties of lipids adsorbed from medium is
      provided by an analysis of kinetic curves of oxidation in toto.

PMID- 16808350
TI  - [Growth and proton-potassium exchange in Enterococcus hirae: protonophore effect
      and the role of oxidation-reduction potential].
AB  - Enterococcus hirae ATCC 9790 are able to grow under anaerobic conditions during
      the fermentation of sugars (pH 8.0) in the presence of the protonophore
      carbonylcyanide-m-chlorophenylhydrazone at a lesser specific growth rate. As
      bacteria grow, the acidification of the external medium and a drop in the redox
      potential from positive to negative (up to -220 mV) values occur. The reducer
      dithiothreitol, which maintains the negative values of the redox potential,
      increases the growth rate and acidification of the medium, recovering thereby the
      effect of the protonophore (without interacting with it). Conversely, the
      impermeable oxidizer ferricyanide, while maintaining positive values of the redox
      potential, inhibits the bacterial growth. These results indicate the role of the
      proton-motive force and importance of reducing processes in bacterial growth. The
      proton-potassium exchange is inhibited by carbonylcyanide-m-chlorophenylhydazone
      but is restored with dithiothreitol. Dithiothreiol is able to substitute the
      proton-motive force; however, ferricyanide and dithiothreitol may also directly
      affect the bacterial membrane.

PMID- 16808351
TI  - [Intensification of extraction by yeast Saccharamyces cerevisiae 1968 of copper
      ions from a solution in magnetic field].
AB  - It was determined whether it is possible to intensify the biosorption of copper
      ions from a copper sulfate solution with yeast Saccharomyces cerevisiae 1968 by
      introducing a metal headpiece into the solution and by applying an external
      magnetic field. The study was carried out in a magnetic field oriented both
      parallel and perpendicular to the axes of the rods (with parallel and
      perpendicular geometry of the system) that make up the headpiece. It was shown
      that the extent of intensification of the extraction of copper ions at different
      geometries of the system differs insignificantly and that the extraction of
      copper ions from the solution occurs by biosorption and cementation onto the
      metal headpiece.

PMID- 16808353
TI  - [Correlation between the sizes of Drosophila populations and parameters of solar
      activity].
AB  - The relationship between the time series of the dynamics of the numbers of
      experimental populations of Drosophila melanogaster at the preimaginal stage and
      three heliogeophysical indices: Wolf numbers, the intensity of the 10.7-cm radio
      flux, and the Kp-index of geomagnetic activity was analyzed. Statistically
      significant data were obtained indicating that the dynamics of the number of the
      populations is related to the heliogeophysical factors, and this relationship
      depends on the phase of the 11-year cycle of solar activity. It was shown that
      the fertility of females and the survival of eggs is stimulated by factors
      associated with solar activity.

PMID- 16808352
TI  - [Effect of low-intensity laser radiation (632.8 nm) on immune cells isolated from
      mice].
AB  - The effect of in vitro exposure to low-power laser light with a power density of
      0.2 mW/cm2 and a wavelength of 632.8 nm induced by helium-neon laser on the
      functional activity of macrophages and splenic lymphocytes was studied. If the
      exposure period did not exceed 60 sec, the stimulation in interleukin-2 (IL-2)
      and nitric oxide (NO) production, as well as an increase in the activity of
      natural killer cells were observed. The increase of irradiation dose by
      prolongation of the exposure duration up to 180 s induced a significant decrease
      in NO production and natural killer cell activity, but IL-2 production was not
      different from the control level. A remarkable decrease in interferon-gamma (IFN
      gamma) production was observed following laser light exposure of cells for 60 or
      180 s, whereas under lower doses (exposure for 5 or 30 sec) IFN-gamma production
      increased. Irradiation of isolated macrophages induced a significant stimulation
      of cellular tumor necrosis factor-alpha (TNF- alpha) production at all dboes
      used, and, what is more important, an enhancement in both TNF-a phaand
      interleukin-6 (IL-6) production was revealed as early as after a 5-s exposure. In
      this case, more prolonged exposure periods, 60 and 180 s, either did not induce
      changes in IL-6 production (in macrophages) or decreased IL-6 production (in
      lymphocytes). Thus, upon in vitro exposure of cells to extremely low-power laser
      light, a basic tendency was observed: short-term irradiation predominantly
      induced stimulation in secretory activity of cells, whereas prolongation of
      exposure mainly induced immunosuppression. The only exception to the rule was a
      change in interleukin-3 (IL-3) production, which decreased after short-time
      exposure, but, on the opposite, increased when the cells were exposed for 180 s.
      In addition, a high sensitivity to extremely low-power laser light was supported
      by expression of the inducible heat shock protein, Hsp70, the effect being
      observed at all doses used, including the exposure for 5 s. At the same time,
      expression of another heat shock protein, Hsp90, was somewhat reduced after
      irradiation of cells with laser light.

PMID- 16808354
TI  - [Connection of the tangents of the regression slope of the heart rate graph with
      linear and nonlinear dynamics in stationary short-time series].
AB  - The connection of the regression slope of heart rate graph (b1) with linear and
      nonlinear dynamics in stationary short-time series (256 points) was studied. A
      new index for the estimation of nonlinear dynamics in stationary short-time
      series was used, which is based on the correlation dimension. The results of the
      study indicated that the dynamics of heart rate in stationary short-time series
      can be represented as the sum of linear (periodic) and nonlinear (stochastic)
      processes. A relation of b1 with both linear and nonlinear dynamics of heart rate
      was found. The formulas for the calculation of absolute and relative (to the
      amplitude of periodic fluctuations) noise levels in heart rate dynamics were
      derived. A comparative analysis of nonlinear dynamics of heart rate in stationary
      short-time series for different functional states of humans was performed. The
      increase in the relative noise level in heart rate dynamics with increasing
      breathing frequency is related not only to a decrease in control breathing
      amplitude but also to an increase in the noise amplitude. The decrease in the
      absolute noise level for nervous excitation, fatigue, and mental stress were
      found. The predominance of nonlinear (stochastic) processes over linear
      (periodic) processes in the relaxed state was established.

PMID- 16808355
TI  - [The contingency of the parameters of the human brain electroencephalograms and
      electromagnetic fields of the Schuman resonator based on monitoring studies].
AB  - The contingency of the variations in the amplitude frequency parameters of the
      main modes of extremely-low-frequency resonances ionosphere waveguide (Shuman
      resonances) and changes in the parameters of human electroencephalograms in the
      range of the frequency "window" (6-16 Hz) was studied. The results of studies in
      the regimes of synchronized monitoring suggest that the contingency of the
      parameters of electroencephalograms and extremely-low-frequency resonances,
      expressed in the parameters of the cross-correlation function, is statistically
      significant and varies from 0.12 to 0.65 at alpha = 0.95. It was found that the
      magnitude of contingency is largely the function of the current value of the
      solar and geomagnetic activity.

PMID- 16808356
TI  - [Survival of amphibian embryos after continuous ultrasound treatment].
AB  - The influence of continuous ultrasound on the embryonic development of grass frog
      Rana temporaria has been investigated. Intact embryos at the blastula stage were
      treated by ultrasound of different frequency (0.88 and 2.64 MHz), intensity (0.05
      1.0 W/cm2), and duration (1-15 min). The treatment with ultrasound of frequency
      0.88 MHz and intensity 0.05 W/cm2 for 1-5 min tended to increase the proportion
      of normally developing embryos up to hatch (10-25% of control). Increasing the
      intensity of ultrasound (0.88 MHz) to 0.7-1.0 W/cm2 and the duration of its
      action to 5-15 min induced the death of almost all of treated embryos. No
      significant differences were found between the development of control embryos and
      embryos treated with ultrasound of middle intensity (0.2-0.7 W/cm2) for 1-5 min.
      The exposure of amphibian embryos to ultrasound of frequency 2.64 MHz and
      intensity 0.05-0.7 W/cm2 for 1-5 min did not change their survival. Increasing
      the intensity of ultrasound (2.64 MHz) to 1.0 W/cm2 and the duration of its
      action to 5 min decreased the number of normal developing embryos (by 35%).

PMID- 16808357
TI  - [New mechanisms of biological effects of electromagnetic fields].
AB  - The production of ATP in mitochondria depends on the magnesium nuclear spin and
      magnetic moment of a Mg2+ ion in creatine kinase and ATPase. This suggests that
      enzymatic synthesis of ATP is an ion-radical process and thus depends on the
      external magnetic field (magnetobiology originates from this fact) and microwave
      fields, which control the spin states of ion-radical pairs and affect the ATP
      synthesis. The chemical mechanism of ATP synthesis and the origin of biological
      effects of electromagnetic (microwave) fields are discussed.

PMID- 16808358
TI  - [The paradox of magnetobiology: analysis and prospects for solution].
AB  - The wording, content, and corollaries of the so-called "kT problem" are
      considered. The problem points to the paradox of the biological effects of weak
      low-frequency magnetic fields. The conventional wording of the problem contains
      implicit assumptions the analysis of which shows their incomplete physical
      validity.

PMID- 16808359
TI  - [Regular measurement--a new method for biophysical experiment].
AB  - A system of quantized relations between the value of the quantity being measured
      and the width of its experimental scattering was experimentally found in the
      results of measurements of rates of various processes. For determining D, the
      square of the ratio of the root-mean-square deviation to the mean value of the
      quantity being measured, particularly long series of stereotypic measurements
      under stable conditions, so-called regular measurements, are carried out. Regular
      changes in biochemical, chemical, and physical quantities show that the D value
      is related by a simple rational expression to the universal dimensionless
      constant D0 whose numerical value was measured with required accuracy. The
      simplicity of the ratios of D and D0 may result from the fact that, during
      regular measurements, the quantum behavior of the system macrodevice-object can
      be revealed.

PMID- 16808360
TI  - [The interaction of lamda-Cro repressor and its mutant covalent S-S-dimer lamda
      CroV55C with symmetric and asymmetric DNA].
AB  - Binding of lamda-Cro protein and mutant CroV55C disulfide bonded dimer to
      synthetic olygonucleotide duplexes were studied using a competition with
      distamycin A. The equilibrium binding constants for lamda operator OR3 and
      duplexes contained symmetry left or right halves of OR3 with one base pair
      deletion or insertion in center of duplex were calculated. The higher binding
      constant for Cro was detected with 17 bp symmetry duplex consist two left halves
      of OR3, for the mutant CroV55C higher binding constant was detected with 16 bp
      derivate of this duplex with the central GC base pair deletion.

PMID- 16808361
TI  - [The surgical treatment of Graves' disease].
AB  - A man aged 80 and three women aged 66, 26, and 39 years respectively, underwent
      surgery for Graves' disease. The first woman had pneumonia and experienced
      thyrotoxic storm. Euthyroidism was restored with antithyroid drugs (ATD) and
      thyroidectomy was performed as ablative treatment for hyperthyroidism. The man
      presented with thyrotoxicosis and had severe Graves' ophthalmopathy. After
      euthyroidism was restored with ATD, he underwent subtotal thyroidectomy. The
      second woman presented with severe thyrotoxicosis but was allergic to ATD. She
      was treated with iodine and beta-blockers after which subtotal thyroidectomy was
      done as an ablative procedure. Medical treatment for hyperthyroidism failed in
      the last patient and, as she had experienced severe psychological disturbances
      during a previous relapse, she too chose surgery as a definitive treatment
      option. In two patients the postoperative course was complicated by early
      hypocalcaemia and one of these patients experienced temporary recurrent laryngeal
      nerve paralysis. Surgery has a limited role in the treatment of Graves' disease.
      In pregnant women with severe ATD-resistant thyrotoxicosis, surgery is the only
      treatment option, while in patients with Graves' orbitopathy surgery may be
      preferable because of its neutral and perhaps even beneficial effects on eye
      symptoms. Large goitre size and thyroid nodules are concomitant reasons for
      choosing surgery, as are allergy to ATD and patients' preference. Lastly, in
      patients who have suffered from severe thyrotoxicosis, surgery provides rapid and
      definitive treatment. Early morbidity following surgery is common and should be
      discussed with the patient.

PMID- 16808362
TI  - [Preconception care: an essential part of the care for mother and child].
AB  - Despite the modernisation of antenatal care in the Western world, the incidence
      of a number of adverse pregnancy outcomes, such as birth defects, low birth
      weight and preterm birth, has not decreased over the past few decades. Since its
      inception at the beginning of the last century, the concept of antenatal care has
      not changed. The first antenatal visit typically starts at the end of the first
      trimester. By this stage of pregnancy organogenesis and early placentation have
      been completed making it almost impossible to reverse any unfavourable exposure
      on the foetus. Preconception care addresses risk factors that are present prior
      to pregnancy. By either eliminating or altering risk factors during this period,
      pregnancy outcome may improve. The goal of preconception care is to optimise the
      quality of foetal, newborn and infant life through primary prevention. With
      regard to genetic conditions the aims of preconception care are more nuanced. The
      principle components of preconception care include (a) risk assessment, (b)
      information and advice on health promotion, (c) specific counselling and (d)
      intervention. The effectiveness of preconception care has been demonstrated in
      women who are at increased risk of adverse pregnancy outcome. In women at low
      risk, however, the usefulness of preconception care has yet to be established.
      The concept of preconception care is relatively simple, logical and promises
      much. For preconception care to be a success, it is crucial to make this form of
      preventive care available to all prospective parents. The Internet could play a
      major part in the dissemination of information that is relevant to a successful
      outcome of pregnancy.

PMID- 16808363
TI  - [Photographs of deceased newborn infants as documentation and as aid in mourning
      process for parents].
AB  - The death of a newborn infant is an extremely emotional event for relatives. Many
      hospitals provide the parents with support, and in some cases a mourning protocol
      is available. Some hospitals offer parents photographs of infants which have died
      around birth. The photographs are often taken by a nurse or doctor on the
      maternity or paediatric ward. It is advisable to draw up a mourning protocol
      which allows professional studio photographs to be taken. As a photograph is
      often the only concrete memento that parents have of their baby, it is important
      for it to be of good quality. The parents decide what they would prefer, but it
      is important to point out to them that their wishes and needs immediately
      following the death may differ to those in the longer term.

PMID- 16808364
TI  - [Diagnostic image (278). A confused man with a cough].
AB  - A 69-year-old man with confusion and a subdural haematoma presented with a cough
      and a radiopaque lesion was visible on chest X-ray. Bronchoscopy revealed a push
      pin, which was removed successfully using a rigid bronchoscope.

PMID- 16808365
TI  - [Quality of a non-subsidised multicentre randomised trial in non-academic
      hospitals; an audit].
AB  - OBJECTIVE: To determine whether a randomised clinical trial in general hospitals
      can be performed in a reliable way without financial support. DESIGN:
      Descriptive. METHOD: The trial involved 1040 patients in whom an inguinal hernia
      had been corrected with a propylene mat in the period 1998-2003. They were
      randomised to either a single dose of prophylactic antibiotics or a placebo. The
      primary outcome measure was 'wound infection during the 3 months after the
      operation'. The audit concerned 98 patients, chosen at random, for whom 3
      investigators from an independent bureau collected data from the patient charts
      and study forms during 3 clinic visits in the period 2000-2003. Whether various
      quality criteria had been fulfilled was assessed on the basis of these data.
      RESULTS: In all 4 participating clinics, approval of the medical ethics
      assessment committees had been obtained. The trial protocol corresponded to the
      consent form. A proper informed consent was obtained from 63/98 patients (64%).
      The last (third) follow-up was missed in 23/98 patients (23%). During the trial,
      the patients who had missed this follow-up were contacted by telephone, which
      succeeded in 98%. The status and trial forms had been filled out completely and
      correctly with regard to the peroperative randomisation forms in 90% of the cases
      and with regard to the follow-up in 75% of the cases. The trial protocol was
      adhered to on almost every point. CONCLUSION: The data collection in the studied,
      not financed trial was adequate, probably as a result of the relatively simple
      questions posed, the easily determinable outcome measure and the efforts expended
      above and beyond the protocol.

PMID- 16808366
TI  - [Fever and exanthema as manifestations of the second stage of syphilis].
AB  - A man aged 30 had been suffering from episodes of fever for several weeks. He had
      diarrhoea and had developed generalized maculopapular exanthema that also
      affected the palms of his hands and soles of his feet. After viral causes were
      excluded the symptoms proved to be caused by syphilis. His condition was
      complicated by uveitis. The patient recovered after a single dose of benzyl
      penicillin and local mydratics and corticosteroid eye drops. The incidence of
      syphilis is rising and its clinical spectrum is broad. Therefore in patients with
      fever and exanthema of unknown origin this disease should be considered. One
      should be aware of the wide variety of complications that can result from
      syphilis.

PMID- 16808367
TI  - [A man with the combination of dry and wet beriberi].
AB  - A 34-year-old alcoholic man had neurological and cardiac symptoms. The patient
      was admitted to the hospital for acute painful sensory disturbances and severe
      weakness of the feet. Neurological and electrophysiological investigation
      revealed axonal sensorimotor polyneuropathy that was most prominent in the legs.
      Cardiac assessment showed signs and symptoms of heart failure due to a high
      output state. Blood analysis showed a low thiamine concentration of 58 nmol/l
      (lower reference limit: 80). Therefore, a diagnosis of combined wet beriberi with
      cardiomyopathy and dry beriberi with axonal polyneuropathy was made. The
      treatment of beriberi is simple and effective and consists of thiamine
      supplementation in conjunction with diuretic treatment. With this approach, the
      patient recovered fully. Patients with beriberi have a good prognosis,
      particularly when the diagnosis is made at an early stage.

PMID- 16808368
TI  - [Deficient information in developing countries: Internet alone is no solution].
AB  - Health-care personnel in developing countries have poor access to information,
      partly because the books are out of date and journals and Internet access are
      lacking, and partly because the information that is available is not appropriate
      for the local situation. There is too little research aimed at the problems of
      the Third World. This is due to a lack of interest in Western countries and
      because local scientists have done too little research. Internet solves the
      problem of access to information for health-care personnel in large hospitals and
      institutes, but there is still a shortage of relevant information for them as
      well. The editorial boards of professional journals could make a contribution by
      facilitating the publication of relevant research. Health-care personnel in rural
      areas will remain dependent upon basic books. This basic component of the
      provision of information should continue to receive attention. For the time
      being, Internet will remain inaccessible for rural health-care personnel. One of
      the initiatives being undertaken in order to improve the provision of information
      to health-care personnel in developing countries is the distribution of the 'blue
      trunk library' of the WHO with a selection of more than 100 basic books in every
      trunk. A number of journals have also taken action: the BMJ Publishing Group
      offers access to its journals free of charge to the 118 poorest countries and the
      Canadian Medical Association Journal provides free copies to libraries in
      developing countries. Moreover, a number ofwebsites have been started with a view
      to enlarging the information for health-care personnel in the Third World.

PMID- 16808369
TI  - [Relief for surviving relatives following a suicide].

PMID- 16808370
TI  - [Young children with serious disorders as a result of late diagnosis of cystic
      fibrosis].

PMID- 16808371
TI  - [The guideline 'Treatment of acute carbon-monoxide poisoning' from doctors in
      clinics with a tank for hyperbaric ventilation].

PMID- 16808372
TI  - [The guideline 'Treatment of acute carbon-monoxide poisoning' from doctors in
      clinics with a tank for hyperbaric ventilation].

PMID- 16808373
TI  - [The first newborn with congenital rubella syndrome during the rubella epidemic
      in The Netherlands in 2004/'05].

PMID- 16808374
TI  - [Recurrent abdominal pain caused by left mesocolic hernia].

PMID- 16808375
TI  - [Scabies outbreak in a hospital and in 8 health-care institutions caused by an
      elderly patient with scabies crustosa].

PMID- 16808376
TI  - [Diagnosis image (260). A woman with a black crust on the face].

PMID- 16808377
TI  - [Main military-and-clinical hospital in the system of medical support of the
      Russian Federation's Armed Forces].
AB  - Burdenko N.N. MMCH is the main hospital, a scientific-and-methodological center
      of medical service concerning prophylaxis-and-treatment spheres, the main
      clinical base of the State istitute of increasing doctors' qualification of RF MD
      and a military-and-medical faculty of the Moscow medical academy by Sechenov I.M.
      The hospital has the greatest experience of treatment of the wounded, sick and
      injured in all wars and armed conflicts with the participation of the Russian
      army. In the hospital's staff there is a unique flying surgical-and-reanimation
      laboratory "Skalpel" for urgent evacuation of the wounded from armed conflicts'
      centers. Almost all types of high technology medical care are provided in the
      hospital. About 6500 of the wounded and the sick obtain such treatment every
      year; 70-80% of the sick having treatment in the hospital are from the group of
      the most severe and complex patients. The hospital has the highest scientific and
      methodological level among hospitals of the Russian Federation's Armed Forces: 48
      doctors and 141 candidates of medical science, those include 21 professors and 12
      docents. It is the main base for new medical equipment and drugs testing to the
      interest of all medical service of the RF AF.

PMID- 16808378
TI  - [Creation and development of Burdenko N.N. MMCH calculating center].

PMID- 16808379
TI  - [Modern aspects of urgent thoracal surgery in Burdenko N.N. MMCH].

PMID- 16808380
TI  - [The main principles of the organization of modern fighting injury radiation
      diagnosis in a diversified in-patient department].
AB  - On the base of accumulated experience in the main principles of the organization
      of modern fighting injury radiation diagnosis authors propose usage of the most
      informatory for the injured method of radiation diagnosis on the first stage of
      the examination. In a specialized diversified hospital the examination of the
      injured should begin with computed tomography enabling to obtain maximum
      information in minimum time about injures got, which is most important for the
      reduction of the preoperational period.

PMID- 16808381
TI  - [The perspectives of roentgenoendovascular surgery development in a diversified
      prophylaxis-and-treatment hospital].
AB  - Great experience of Burdenko N.N. Main military-and-clinical hospital
      angiographic research department's work is systemized. On the base of
      retrospective analysis of 1621 medical cards the evaluation of the nearest and
      distant treatment results, its efficiency, and importance of
      roentgenoendovascular surgery in the system of specialized medical care is
      presented. Conclusions on the far perspectives of this direction's development in
      a diversified hospital were drawn..

PMID- 16808383
TI  - [Optimization of diagnosis and treatment for acute pancreatitis].

PMID- 16808382
TI  - [Regional anesthesia in practice of a military doctor-and-anesthesiologist].

PMID- 16808384
TI  - [Subatrophic status of mucous tunic of pharynx in servicemen and principles of
      its treatment].

PMID- 16808385
TI  - [Acute renal failure: mechanism of development, diagnosis and treatment].

PMID- 16808386
TI  - [Some organizational aspects of treatment for patients with terminal renal
      failure having programmed hemodialysis].

PMID- 16808387
TI  - [Burdenko N.N. main military-and-clinical hospital in military-and-medical museum
      funds].
AB  - Burdenko N.N. Main military-and-clinical hospital fund in Military-and-medical
      museum the Russian Federation's Ministry of defense amounts to over 300 units of
      keeping - written and material sources, photodocuments in connection with the
      first Russian state medical and educational organization's activity.

PMID- 16808388
TI  - [Some from history of Burdenko N.N. main military-and-clinical hospital
      infectious department].

PMID- 16808389
TI  - [Stages of stomatology and maxillofacial surgery development in the main military
      hospital].

PMID- 16808390
TI  - ["To work here is a great honour and huge responsibility" (An interview with a
      colonel of medical service Ardashev V.N.)].

PMID- 16808391
TI  - [Urea as an indicator of anthropogenic pollution of water of swimming pools].
AB  - The sports swimming pools of Volgograd were examined for the levels of urea. All
      the study swimming pools were found to have a level of urea in the range of 28-80
      micromol/l; which is about 10-15 times higher that its background level in the
      natural water reservoirs. Analysis of urea in the water of a swimming pool is
      proposed as a sensitive and simple test for fresh man-made water pollution.

PMID- 16808392
TI  - [Assessment of a risk to health as a way of reducing congenital and hereditary
      pathology in children].
AB  - Based on the data available in the literature and his own findings, the author
      determines the urgency of study of environment-dependent diseases in a poor
      ecological area. The analytical survey presents data available about the
      ecological situation in the town of Omsk, a center of chemical and oil-refining
      industries of Western Siberia from 1997 to 2003. Particular emphasis is laid on a
      child's responses to the combined exposure to unfavorable environmental factors.
      The signs characterizing ecopathology are considered and the main principles of
      the treatment and prevention of environment-dependent diseases are given.

PMID- 16808393
TI  - [The adaptation as a health index].
AB  - Search for available and informative methods for assessing human health indices
      is a topical problem of Russian public health care. The present paper proposes to
      use the computer program of a cyclic adaptive reaction change model--STAT (the
      Hem variant) for the assessment of the body's adaptability, an important index of
      individual and populational health. An attempt was made to develop and form new
      approaches to determining the adaptability in schoolchildren from their
      leukogram.

PMID- 16808394
TI  - [A modification factor of spontaneous chromosomal aberrations in miner's towns
      and settlements].
AB  - The level and qualitative spectrum of spontaneous chromosomal aberrations (CA)
      were comparatively analyzed in the lymphocytes of 655 children and adolescents
      from the Kemerovo Region. The presented sample was divided into 3 groups
      according to the type of an inhabited locality: 1) small miner's towns; 2) large
      industrial towns; and 3) rural localities. The maximum frequency of CA (3.77 +/-
      0.22%) was noted in a group of dwellers in the miner's towns; its minimum
      frequency (2.68 +/- 0.17%) among the rural inhabitants. The significant
      clastogenic effects (including the markers of radiation exposure) were detected
      in the miner's towns located in the southern part of the region, which
      represented mountain and submountain areas. At the same time, in the northern and
      western parts of the Kemerovo Region, the average frequencies of CA in children
      and adolescents did not exceed the control background values. Thus, the residence
      in the inhabited localities specializing in mining is not a factor of absolute
      toxicogenetic risk.

PMID- 16808395
TI  - [Human health in the space rocket-making areas: medical and environmental
      aspects].
AB  - The paper deals with the problems of medical and ecological escorts of space
      rocket-making activities. The properties of one of the highly toxic components of
      propellant - asymmetric dimethylhydrazine as a substance assigned to a class of
      ecological toxicants, are considered. The data obtained on implementing the
      program for a study of the health status in the population living not far from
      the asymmetric dimethylhydrazine-polluted areas are presented. The authors
      propose to consider a package of measures that can apply the systems approach to
      securing the safety of the population to live and work in areas under space
      rocket making activities, which is based on the prevention principle provided by
      the Rio de Janeiro Environment and Development Declaration.

PMID- 16808396
TI  - [Mathematical simulation of accumulation of opportunistic micromycetes in
      petroleum-polluted soils].
AB  - The impact of pollution of different types of soils (leached chernozem, grey wood
      and dark-grey wood soils) with petroleum and its products on the size, species
      specific composition, and accumulation of opportunistic micromycetes was studied
      in long-term field microallotment and laboratory conditions. Petroleum and its
      refining products were shown to increase the size of micromycetes and to change
      their structure and species diversity. A mathematical model has been developed,
      which describes the time course of changes in the size of mushroom propagules
      under different environmental conditions.

PMID- 16808397
TI  - [The health status of the rural population living in the areas contiguous with
      industrial towns].
AB  - Exposed to environmental pollution with emissions from industrial enterprises,
      the population of their contiguous rural areas faces a high risk of their health.
      The studies of the health status of the population from the contiguous rural
      areas versus that from the non-contiguous ones have established that measurements
      of a risk to the children's health revealed the highest risk among the contiguous
      areas in the Sterlitamaksky district and the least risk among the non-contiguous
      ones in the Askinsky district. The markers of carcinogenic ill-being in the
      contiguous rural areas were the incidence of cancer of the lip, esophagus,
      stomach, larynx, cervix uteri, uterine appendages, and prostate and leukemia. The
      high risk of cancer of the lip and esophagus in the control area and in other non
      contiguous rural areas may be accounted for by the bad life-style in villagers,
      alcohol abuse, and smoking.

PMID- 16808398
TI  - [The problem of iodine deficiency in the Tver Region: sociohygienic aspects].

PMID- 16808399
TI  - [The health status of workers while mining and enriching chrysotile asbestos:
      hygienic aspects].

PMID- 16808400
TI  - [Current problems of occupational morbidity on the railway transport].
AB  - The paper discusses the present working conditions on railway transport, by using
      the results of employee rating, characterizes railway services showing the
      greatest magnitude of adverse and dangerous factors of working conditions. It
      also characterizes occupational morbidity in railway transport workers over 5
      years (1999-2003) and by hazards problems of occupational morbidity and by basic
      services: locomotive, wagon, and track ones. The paper also presents the rates of
      disability due to occupational diseases, characterizes the priorities of
      prevention of occupational diseases on the railway transport.

PMID- 16808401
TI  - [Ophthalmological assessment of professionally significant functions in persons
      undergone laser myopia correction].
AB  - Professionally significant functions (visual acuity, color vision and its
      parameters, and dark adaptation and its parameters) were determined in moderate
      and severe myopia before and after its excimer laser correction by the LASIK
      method: in early (1, 3 months) and late (6, 12 months) periods after surgery to
      decide where the operated persons are allowed to have the jobs associated with
      railway traffic safety. Sixty-one patients with moderate and severe myopia and 23
      control individuals were examined at the Moscow Research and Technological
      Complex "Eye Surgery". The examinations have demonstrated that the values of
      visual acuity, color vision, and dark adaptation considerably improved. Whether
      the persons undergone excimer laser myopia correction are allowed to have the
      jobs associated with railway transport safety should be individually decided, by
      taking into account the postoperative recovery of professionally significant
      visual functions.

PMID- 16808402
TI  - [Higher mental functions of the workers of the Ministry of Internal Affairs under
      extreme professional activities].
AB  - Mental (cognitive) processes were analyzed in officers from different
      subdivisions of internal affairs bodies during their service. The study
      parameters were found to be in the normal range, but at the same time there were
      significant differences between occupational groups. The more the length of
      service was, the more verbal information was kept in mind in officers from
      criminal investigation and inquiry departments and district militia inspectors.
      With more service, there is an increase in mental fatigue and a reduction in the
      level of combinatorial analysis in all study groups. The findings enhance the
      capacities of solving the problems of occupational selection, staff arrangement,
      timely psychological correction and prevention of mental diseases.

PMID- 16808403
TI  - [The impaired upper respiratory environment as a criterion for a risk of
      respiratory diseases in firemen].
AB  - Microbiocenoses were qualitatively and quantitatively determined; the
      cytomorphological parameters of the upper respiratory tract mucosae were studied,
      and the concentrations of SIgA were measured in the saliva of firemen. In the
      latter, nonspecific infection resistance was found to diminish due to the
      influence of poor occupational factors. A strong correlation was found between
      the influencing factors and the development of upper airway diseases; the latter
      were greatly affected by occupational factors.

PMID- 16808404
TI  - [Hygienic assessment of actual nutrition in primary class teachers from Ryazan
      comprehensive schools].
AB  - The present study is part of a comprehensive study performed by the Ryazan State
      Pedagogical University among teachers in different regions of the European part
      of Russia. It gives a hygienic assessment of actual nutrition in teachers of
      primary forms from Ryazan comprehensive schools, which was studied continuously
      during 7 days by questionnaire surveys of 307 teachers in winter and summer. The
      total dietary intake of protein was less than the normal physiological values in
      16.1% of the teachers, higher in 53.4%, and normal in 30.5%. That of fat was less
      than the normal physiological value in 30.1% and greater in 25.8%. The dietary
      intake of carbohydrates was less than the normal physiological value in most
      cases (72.6%). In the primary-form teachers, the daily calorie intake was less
      than the normal physiological value. There was the highest deficiency of vitamins
      B1, PP, and C. Analysis of mineral composition indicated that calcium and
      magnesium were most deficient. Overweight was detected in 32.3% of the teachers.
      It is concluded that there is a need for balanced feeding in teachers, by
      expanding the assortment of full-value natural foods.

PMID- 16808405
TI  - [Nutrition at the preschool institutions: organizational aspects].
AB  - Three meals a day with a high-calorie afternoon snack (instead of afternoon snack
      and supper) moved an hour later than usual are most adequate and physiological
      for preschool children who stay at a preschool institution for 10.5 to 12 hours.
      This is achieved by a reduced food assortment that covers 85% of daily energy
      losses in a child. Control of nutrition adequacy in the preschool institution by
      a bookkeeping cumulative list is rather effective and informative. A month
      official control of the nutritive value of a mean daily menu apportionment does
      not achieve the main objective of a control - to maintain the nutrition balance
      of meals and their correction with foods. While republishing normative documents
      on nutrition at the preschool institutions, sanitary epidemiological surveillance
      bodies wish to be overcautious, by expanding the list of products and dishes
      prohibited for use, thus releasing the workers of the nutrition unit of a
      preschool institution from responsibility for safe nutrition, but this frequently
      causes damage to nutrition itself.

PMID- 16808406
TI  - [Impact of present-day forms of organization of physical education on the health
      status of preschool children].
AB  - During a natural hygienic experiment, the physical development, psychomotor
      activity, exercise performance, and readiness were evaluated in 6-year-old
      children, in whom physical education had been organized by routine and
      experimental programs, including health-improving swimming in the indoor pool of
      a preschool educational establishment. Exercises built up on the principle of
      plot-role playing games, by using the developing corrective exercises and
      psychological and pedagogical escort, were established to be highly effective.
      The proposed methods contribute to the timely harmonious development of a child,
      his movement characteristics, positively affect the neurofunctional status, by
      ensuring the optimum psychomotor development, and maintain a high exercise
      performance.

PMID- 16808407
TI  - [Evaluation of the physical development of adolescents of call-up age and armed
      forces personnel].
AB  - At present, there are no methods for evaluating the physical development of
      subjects of call-up age, which present problems during recruitment of those who
      can adequately cope with set problems for armed forces. A large number of
      conscripts were examined, by using anthropometry, physiometry, the Stange test,
      and exercise test. A classification system was developed on the basis of
      mathematical models derived by means of discriminant analysis. The procedure
      tested by the authors could determine the informative value of indices and
      identify the most important indices for the objective evaluation of an
      individual's physical development. The software implementation of the proposed
      approaches will permit a rapid evaluation of physical development both during the
      work of a draft board' and in the military unit.

PMID- 16808408
TI  - [Psychophysiological features in 4-to-10-year-old children with visual
      dysfunction].

PMID- 16808409
TI  - [The health status of pupils from different-profile schools].
AB  - The paper presents the results of prenosological examination of 1246 pupils from
      different-profile schools by computer-aided electrostructurography. The least
      children with morphofunctional changes in the viscera and systems were found at
      sports school. Gastrointestinal functional changes (intestinal dysfunction,
      biliary dyskinesia) and structural disorders (chronic gastritis, chronic colitis,
      posttoxic hepatic changes) hold the lead in the structure of total morbidity. In
      a great deal of the examinees, functional changes are frequently associated with
      morphological disorders within one or several systems.

PMID- 16808410
TI  - [New approaches to integrating prophylactic and health-improving technologies in
      an educational process].

PMID- 16808411
TI  - [Hygienic assessment of textbooks for educational establishments of different
      types].
AB  - The role of hygienic parameters of prints in the development of fatigue and this
      or that abnormality in schoolchildren of today has been inadequately studied.
      Practically every three or two textbooks on the humanities, analyzed by the
      authors, show breaches of the orders of educational publishing products; they are
      much less significantly encountered in the textbooks on natural sciences and, in
      isolated instances, in those on mathematical sciences. Thus, due to the
      variations in their weight, the lettering of a body text, high component
      complexity and abstractedness, the textbooks are a risk factor for visual,
      nervous, and musculoskeletal diseases among pupils of educational establishments,
      particularly those of the innovation type. The problems associated of the present
      day textbook are of no hygienic order, although they may exert a considerable
      impact on pupils' efficiency.

PMID- 16808412
TI  - [Identification of risk factors for respiratory diseases in adolescents from an
      industrial city].
AB  - The prevalence of respiratory disease and the spread of risk factors were studied
      in adolescents living in Saratov. Respiratory diseases held the lead among other
      classes of diseases in young people; these diseases were more prevalent in
      adolescents than in children and adults. Examination of their outpatient cards
      revealed defects in the management of pulmonological patients. Screening could
      identify the most important risk factors of respiratory diseases (such as poor
      housing and living conditions, smoking, and recurrent acute respiratory viral
      infections (ARVI)) and make up three groups of patients: 1) those at risk for
      respiratory diseases and frequently ARVI; 2) those with acute respiratory
      diseases; and 3) those with chronic respiratory diseases.

PMID- 16808413
TI  - [Comparative analysis of childhood morbidity depending on the type of feeding].
AB  - Retrospective and prospective studies were made in 1248 infants of the first year
      of life and in 642 children aged 7 to 14 years who lived in Kirov and its region.
      The purpose of the study was to evaluate the impact of different types of feeding
      on their morbidity. The children who had received an artificial feeding were
      ascertained to be more frequently ill both in their first year of life and at an
      older age.

PMID- 16808414
TI  - [The morphofunctional state of the respiratory system in 18-27-year-old persons
      living in Uzbekistan].
AB  - The morphofunctional state of the respiratory system was studied in 2104 male
      Uzbeks aged 18-27 years from rural and urban areas. The chest circumference,
      frontal and sagittal diameters, respiratory excursion and vital capacity, breath
      holding were found to be higher in the rural males in almost all age groups than
      in the urban ones, suggesting that the latter had a low activity. The increase in
      the diametrical chest sizes mainly occurred by the asthenic type in the rural
      males and by the hyperstenic type in the urban ones. Unlike the urban males, the
      rural ones showed a more developed respiratory system and its rather higher
      functional and adaptive capacities. There was a close correlation of the total
      sizes of the body with the morphological signs of the chest and their low
      correlation with the external respiratory functional parameters.

PMID- 16808415
TI  - [Monitoring methodology of the educational environment and schoolchildren's
      health].

PMID- 16808416
TI  - [To the establishment of the sizes and organization of sanitary-hygienic zones].

PMID- 16808417
TI  - [Basic results of the 60th anniversary (1946-2006) pedagogical and scientific
      activities of the Department of General Hygiene, Moscow State Medical
      Stomatological University].

PMID- 16808418
TI  - [Primary care: need for research].

PMID- 16808419
TI  - [Ongoing professional development. The semFYC portfolio, a learning tool for
      professional improvement].

PMID- 16808421
TI  - Lifestyle counseling in type 2 diabetes prevention: a case study of a nurse's
      communication activity to produce change talk.
AB  - As a case study, this article describes a nurse's communication activity,
      focusing on change talk during lifestyle counseling in primary healthcare. All
      videotaped counseling sessions with a single patient within a period of two years
      were transcribed verbatim. In the analysis, an emphasis was placed on the nurse's
      communication activity that produced change talk, how the nurse initiated change
      talk, and how the patient received it. The observations provide evidence that the
      dilemma of simultaneously maintaining professional authority and patient
      perspective leads to sensitivity in lifestyle counseling. Three categories of
      change talk were identified: rejected, restrictive, and expansive change talk.
      Producing change talk is a very demanding task for counselors. It is best
      produced when the nurse stays within the patient's frame of reference with a
      combination of reflective, change-inducing questions, encouraging assessments and
      conversational space. On the basis of our results, we suggest that nurses need
      training to identify and to encourage patients' change talk and to communicate
      flexibly according to patients' values during lifestyle counseling. In addition,
      in order to insist on change talk, we need to demonstrate how change talk could
      be carried out so that nurses could orient to it.

PMID- 16808422
TI  - Representations of people with HIV and hepatitis C in editorials of medical
      journals: discourses and interdiscursive relations.
AB  - HIV and hepatitis C are blood-borne viruses that cause chronic diseases and
      affect (in parts of the developed world) predominantly groups that are
      marginalized and discriminated against: gay men and injecting drug users,
      respectively. This paper compares the representation of people with HIV and
      hepatitis C in editorials of medical journals between 1989 and 2001. Analysis is
      informed by critical discourse analysis and systemic functional linguistics.
      Hepatitis C editorials draw almost exclusively on the discourse of biomedicine,
      and patients are either absent or objects in medical procedures. In HIV
      editorials, a variety of other discourses are integrated into the discourse of
      biomedicine, thereby creating multidimensional representations of people with HIV
      as patients and agents in medical procedures, involved in decision making,
      affected by economic factors, social and cultural issues. The paper discusses the
      role of the gay community in discursive change and argues that discursive
      diversity in the representation of people infected with HIV and hepatitis C in
      medical journals is necessary for health policy, the professional development of
      healthcare providers, and media reporting to the general public.

PMID- 16808423
TI  - When psychotherapists disclose personal information about themselves to clients.
AB  - Psychotherapists sometimes disclose personal information to their clients during
      therapeutic sessions. We report here our analysis of how these 'therapist self
      disclosures' are done. In a sample of 15 sessions involving four therapists, we
      find that all therapists use them sparingly and some not at all. When they do,
      they 'match' something in the client's preceding turn. Vehicles for the match can
      range from comparatively simple agreements to more complicated 'second stories',
      which use analogies from the therapists' own current life. We find that these
      'personal' disclosures are invariably rather ordinary but are made to bear
      visibly on the therapeutic business at hand, though not always in obvious ways.
      The ordinariness of therapist's self-disclosures underpins what seems to be one
      of their main actions-to 'normalize', for a number of disparate local
      interactional contingencies, the clients' experience. We discuss the practice of
      using one's own life experiences to bear on one's client's troubles, noting the
      recurrent features of extreme case formulations and explicit recipient design. We
      conclude with a brief discussion of the relation between our analyses and those
      which might be offered by members of the therapeutic community.

PMID- 16808424
TI  - The deep play of medicine: discursive and collaborative processing of evidence in
      medical problem solving.
AB  - Ethnographic research was conducted in the thoracic ward of a Norwegian
      university hospital in order to study collaborative medical problem solving. As a
      general principle, evidence-based medicine is supposed to lead the process of
      medical problem solving. However, medical problem solving also requires evidence
      of a different kind. This is the more concrete form of evidence, such as X rays
      and other representations, that guides medical practice and makes sure that
      decisions are grounded in sound empirical facts and knowledge. In medicine,
      'evidence' is on the one hand an abstract category; on the other hand, it is a
      tool that is practically enacted during the problem-solving work. Medical
      evidence does not 'show itself'. As such it has an emergent quality. Medical
      evidence has to be established and made practically useful in the collaborative
      settings by the participants in order to make conclusions about diagnoses and
      treatment. Hence, evidence is an interactional product; it is discursively
      generated and its applicability requires discourse. In addition, the production
      of medical evidence requires more than medical discourse and professional
      considerations. This paper looks at the production processes and use of medical
      evidence and the ambiguous meaning of this term in practical medicine.

PMID- 16808425
TI  - Media(ted) fabrications: how the science-media symbiosis helped 'sell' cord
      banking.
AB  - This paper considers the problematic role of the science-media symbiosis in the
      dissemination of misleading and emotionally manipulative information regarding
      services offered by CordBank, New Zealand's only umbilical cord blood banking
      facility. As this case study illustrates, the growing reliance of health and
      science reporters on the knowledge capital of medical specialists, biogenetic
      researchers, and scientists potentially enhances the ability of 'expert' sources
      to set the agenda for media representations of emerging medical and scientific
      developments, and may undermine the editorial independence of journalists and
      editors, many of whom in this case failed to critically evaluate deeply
      problematic claims regarding the current and future benefits of cord banking.
      Heavy reliance on established media frames of anecdotal personalization and
      technoboosterism also reinforced a proscience journalistic culture in which
      claims by key sources were uncritically reiterated and amplified, with
      journalistic assessments of the value of cord banking emphasizing potential
      benefits for individual consumers. It is argued that use of these media frames
      potentially detracts from due consideration of the broader social, ethical,
      legal, and health implications of emerging biomedical developments, along with
      the professional, personal, and increasingly also financial interests at stake in
      their public promotion, given the growing commercialization of biogenetic
      technologies.

PMID- 16808426
TI  - An enquiry into scientific and media discourse in the MMR controversy: authority
      and factuality.
AB  - In this paper, we investigate two scientific articles at opposite ends of the MMR
      debate-Wakefield et al. (1998) (which started the debate) and Taylor et al.
      (1999)-and four media articles published to inform the public of the results of
      these two scientific studies. Because people need to assess truth claims about
      health risks, communicators seek to establish their believability in two ways:
      authority (i.e., the attribution of scientific claims to sources that may be
      perceived as believable because of their status) and factuality (i.e., the
      moderating, limiting, or highlighting of truth claims). The importance of
      authority was confirmed by the media texts' preference for direct quotes and
      messages about what people ought to do, especially at the beginning of the
      debate. Our most significant find, however, relates to two important indicators
      of factuality: avoidance of vague references and high use of epistemic modals,
      where Wakefield et al. displays a pattern not at all different from the media
      texts and opposite to that expected from a scientific text. That Wakefield et al.
      stands out in the majority of indicators investigated is of interest in view of
      its controversial position in the MMR debate and worthy of further study.

PMID- 16808427
TI  - What healthcare students do with what they don't know: the socializing power of
      'uncertainty' in the case presentation.
AB  - Healthcare students learn to manage clinical uncertainty amid the tensions that
      emerge between clinical omniscience and the 'truth for now' realities of the
      knowledge explosion in healthcare. The case presentation provides a portal to
      viewing the practitioner's ability to manage uncertainty. We examined the
      communicative features of uncertainty in 31 novice optometry case presentations
      and considered how these features contributed to the development of professional
      identity in optometry students. We also reflected on how these features compared
      with our earlier study of medical students' case presentations. Optometry
      students, like their counterparts in medicine, displayed a novice rhetoric of
      uncertainty that focused on personal deficits in knowledge. While optometry and
      medical students shared aspects of this rhetoric (seeking guidance and deflecting
      criticism), optometry students displayed instances of owning limits while medical
      students displayed instances of proving competence. We found that the nature of
      this novice rhetoric was shaped by professional identity (a tendency to assume an
      attitude of moral authority or defer to a higher authority) and the clinical
      setting (inpatient versus outpatient settings). More explicit discussions
      regarding uncertainty may help the novice unlock the code of contextual forces
      that cue the savvy member of the community to sanctioned discursive strategies.

PMID- 16808428
TI  - Commentary 1. 'Telling the truth about genomics': hype and hope.

PMID- 16808429
TI  - Commentary 2. 'Telling the truth about genomics': legitimating a third voice: the
      role of philosophy in societal debates.

PMID- 16808430
TI  - Commentary 3. 'Telling the truth about genomics': toward a societal agenda for
      genomics research.

PMID- 16808432
TI  - Recognition of a cervical cancer derived tumor cell line by a human
      papillomavirus type 16 E6 52-61-specific CD8 T cell clone.
AB  - The E6 and E7 proteins of high-risk human papillomavirus (HPV) types are thought
      to be the ideal sources of antigens for immunotherapy for cervical cancer since
      they are expressed by the tumors and not by normal cells. We recently described
      new HPV 16 epitopes, including the E6 52-61 peptide restricted by HLA class I
      molecule B57. Primary tumor cell lines were established from three HLA-B57
      positive, HPV 16 positive cervical cancer patients, and their recognition by a E6
      52-61 specific CD8+ T cell clone was determined using a chromium release assay
      and an IFN-gamma enzyme-linked immunospot (ELISPOT) assay. The recognition of
      homologous epitopes contained in other high-risk HPV types (18, 31, 33, 35, 39,
      45, 51, 52, 56, 58, 59, 68, and 73) was also examined at the peptide level. A low
      level of killing of two of the tumor cell lines derived from the three patients
      was demonstrated using a chromium release assay. The level of killing of one of
      these tumor cell lines was enhanced upon treatment with IFN-gamma and/or the
      addition of antigen. This tumor cell line also induced measurable IFN-gamma
      secretion. The recognition of homologous epitopes from HPV 35, 39, 45, 51, and 73
      was detected in an ELISPOT assay. Therefore, the HPV 16 E6 52-61 epitope appears
      to be at least weakly expressed by tumor cell lines derived from cervical cancer,
      and the HPV 16 E6 52-61-specific T cell clone can recognize homologous peptides
      derived from other high risk HPV sequences.

PMID- 16808433
TI  - Quantitative analysis of modified proteins and their positional isomers by tandem
      mass spectrometry: human histone H4.
AB  - Here we show that fragment ion abundances from dissociation of ions created from
      mixtures of multiply modified histone H4 (11 kDa) or of N-terminal synthetic
      peptides (2 kDa) correspond to their respective intact ion abundances measured by
      Fourier transform mass spectrometry. Isomeric mixtures of modified forms of the
      same protein are resolved and quantitated with a precision of </=5% using the
      relative ratios of their fragment ions, with intact protein ions created by
      electrospray greatly easing many of the systematic biases that more strongly
      affect small peptides (e.g., differences in ionization efficiency and ion m/z
      values). The ion fragmentation methods validated here are directly extensible to
      intact human proteins to derive quantitative information on the highly related
      and often isomeric protein forms created by combinatorial arrays of
      posttranslational modifications.

PMID- 16808434
TI  - Probabilistic quotient normalization as robust method to account for dilution of
      complex biological mixtures. Application in 1H NMR metabonomics.
AB  - For the analysis of the spectra of complex biofluids, preprocessing methods play
      a crucial role in rendering the subsequent data analyses more robust and
      accurate. Normalization is a preprocessing method, which accounts for different
      dilutions of samples by scaling the spectra to the same virtual overall
      concentration. In the field of 1H NMR metabonomics integral normalization, which
      scales spectra to the same total integral, is the de facto standard. In this
      work, it is shown that integral normalization is a suboptimal method for
      normalizing spectra from metabonomic studies. Especially strong metabonomic
      changes, evident as massive amounts of single metabolites in samples,
      significantly hamper the integral normalization resulting in incorrectly scaled
      spectra. The probabilistic quotient normalization is introduced in this work.
      This method is based on the calculation of a most probable dilution factor by
      looking at the distribution of the quotients of the amplitudes of a test spectrum
      by those of a reference spectrum. Simulated spectra, spectra of urine samples
      from a metabonomic study with cyclosporin-A as the active compound, and spectra
      of more than 4000 samples of control animals demonstrate that the probabilistic
      quotient normalization is by far more robust and more accurate than the
      widespread integral normalization and vector length normalization.

PMID- 16808435
TI  - Liver-specific functional studies in a microfluidic array of primary mammalian
      hepatocytes.
AB  - Nearly half a billion dollars in resources are lost each time a drug candidate is
      withdrawn from the market by the Food and Drug Administration (FDA) for reasons
      of liver toxicity. The number of late-phase drug developmental failures due to
      liver toxicity could potentially be reduced through the use of hepatocyte-based
      systems capable of modeling the response of in vivo liver tissue to toxic
      insults. With this article, we report progress toward the goal of realizing an
      array of primary hepatocytes for use in high-throughput liver toxicity studies.
      Described herein is the development of a 64 (8 x 8) element array of microfluidic
      wells capable of supporting micropatterned primary rat hepatocytes in coculture
      with 3T3-J2 fibroblasts. Each of the wells within the array was continuously
      perfused with medium and oxygen in a nonaddressable format. The key features of
      the system design and fabrication are described, including the use of two
      microfluidic perfusion networks to provide the coculture with an independent and
      continuous supply of cell culture medium and oxygen. Also described are the
      fabrication techniques used to selectively pattern hepatocytes and 3T3-J2
      fibroblasts within the wells of the array. The functional studies used to
      demonstrate the synthetic and metabolic capacity of the array are outlined in
      this article. These studies demonstrate that the hepatocytes contained within the
      array are capable of continuous, steady-state albumin synthesis (78.4 microg/day,
      sigma = 3.98 microg/day, N = 8) and urea production (109.8 microg/day, sigma =
      11.9 microg/day, N = 8). In the final section of the article, these results are
      discussed as they relate to the final goal of this research effort, the
      development of an array of primary hepatocytes for use in physiologically
      relevant toxicology studies.

PMID- 16808436
TI  - Optimization of a microfluidic mixer for studying protein folding kinetics.
AB  - We have applied an optimization method in conjunction with numerical simulations
      to minimize the mixing time of a microfluidic mixer developed for protein folding
      studies. The optimization method uses a semideterministic algorithm to find the
      global minimum of the mixing time by varying the mixer geometry and flow
      conditions. We describe the minimization problem and constraints and give a brief
      overview of the optimization algorithm. We present results of the optimization,
      including the optimized geometry and parameter sensitivities, and we demonstrate
      the improvement in mixing performance with experiments using microfabricated
      mixers. The dye-quenching experiments of the original and optimized mixer designs
      show respective mixing times of 7 and 4 mus, a 40% reduction. The new design also
      provides more uniform mixing across streamlines that enter the mixer. The
      optimized mixer is the fastest reported continuous flow mixer for protein
      folding.

PMID- 16808437
TI  - Impact of analytical bias in metabonomic studies of human blood serum and plasma.
AB  - Concurrent with the explosion in the number of publications reporting biomarker
      discovery by profiling technologies, such as proteomics and pattern recognition,
      has been the increase in evidence highlighting the susceptibility of these
      approaches to analytical and experimental bias. The work presented here addresses
      these timely issues by delivering a detailed characterization of the effect of
      common sources of bias in clinical studies on serum and plasma profiles generated
      by a key technology in metabonomics, NMR spectroscopy. Specifically, differences
      in composition when blood samples were collected onto and in the absence of ice,
      over a series of serum-clot contact times, the stability of NMR-prepared samples
      over time and the effect on the metabolic profile of freeze-thawing were
      examined. While differences between individuals were far greater than variation
      from any other experimental factor, each of the conditions examined did cause
      slight alterations to the NMR profile that could produce a systematic bias.
      Variation due to clotting time caused changes in energy metabolites, which were
      delayed by ice with no other spectral effects. Room-temperature stability and
      hence NMR spectral repeatability were high (<1% intrasample variation). Higher
      molecular weight species such as lipoproteins were more susceptible to the
      variations present in the examined factors. These observations have implications
      for profiling study design, and hence, our results form a new and valuable
      resource for those attempting clinical metabolic profiling, for regulatory
      agencies involved in the licensing of clinical tests and in the generation of
      international reporting standards for metabonomics.

PMID- 16808438
TI  - Characterization of a second-generation focal-plane camera coupled to an
      inductively coupled plasma Mattauch-Herzog geometry mass spectrograph.
AB  - A second-generation Faraday-strip array detector has been coupled to an
      inductively coupled plasma Mattauch-Herzog geometry mass spectrograph, thereby
      offering simultaneous acquisition of a range of mass-to-charge ratios. The second
      generation device incorporates narrower, more closely spaced collectors than the
      earlier system. Furthermore, the new camera can acquire signal on all collectors
      at a frequency greater than 2 kHz and has the ability to independently adjust the
      gain level of each collector. Each collector can also be reset independently.
      With these improvements, limits of detection in the hundreds of picograms per
      liter for metals in solution have been obtained. Some additional features, such
      as a broader linear dynamic range (over 7 orders of magnitude), greater resolving
      power (up to 600), and improved isotope ratio accuracy were attained. In
      addition, isotope ratio precision as low as 0.018% RSD was achieved.

PMID- 16808439
TI  - ESI-MS compatible permanent coating of glass surfaces using poly(ethylene glycol)
      terminated alkoxysilanes for capillary zone electrophoretic protein separations.
AB  - Thin poly(ethylene glycol) silane (PEG-silane) coatings formed from N
      (triethoxysilyl propyl)-O-poly(ethylene oxide) urethane with different chain
      lengths of poly(ethylene glycol) (MW 750 and 4000-5000) are used to modify glass
      microfluidic channels and fused-silica capillaries for electrophoretic
      separations of proteins. These coatings combine three important properties, which
      make them favorable for proteomic analyses including reduction of protein
      adsorption, compatibility with mass spectrometry due to their stability, and the
      ability to control the magnitude of electroosmotic flow (EOF). The coatings have
      been successfully used in microfluidic chips and fused-silica capillaries for
      separation of protein sample mixtures under low EOF conditions. The long-chain
      and mixed PEG-silane coatings suppress electroosmotic flow by more than 90%,
      whereas the short-chain PEG silane suppresses EOF by 65-75% at pH values of 3-9.
      The long-chain and mixed PEG-silane coatings are suitable for low EOF
      applications or for cases where negative effects of EOF are to be minimized.
      Efficient separations of unlabeled basic proteins at low pH and FITC-labeled
      proteins at high pH were achieved, as well as excellent stability for at least
      200 electrophoretic runs. Additionally, these covalent coatings produce no
      detectable background ions in ESI-MS, making them compatible with on-line mass
      spectrometry.

PMID- 16808440
TI  - MET-IDEA: data extraction tool for mass spectrometry-based metabolomics.
AB  - A current and significant limitation to metabolomics is the large-scale, high
      throughput conversion of raw chromatographically coupled mass spectrometry
      datasets into organized data matrices necessary for further statistical
      processing and data visualization. This article describes a new data extraction
      tool, MET-IDEA (Metabolomics Ion-based Data Extraction Algorithm) which surmounts
      this void. MET-IDEA is compatible with a diversity of chromatographically coupled
      mass spectrometry systems, generates an output similar to traditional
      quantification methods, utilizes the sensitivity and selectivity associated with
      selected ion quantification, and greatly reduces the time and effort necessary to
      obtain large-scale organized datasets by several orders of magnitude. The
      functionality of MET-IDEA is illustrated using metabolomics data obtained for
      elicited cell culture exudates from the model legume, Medicago truncatula. The
      results indicate that MET-IDEA is capable of rapidly extracting semiquantitative
      data from raw data files, which allows for more rapid biological insight. MET
      IDEA is freely available to academic users upon request.

PMID- 16808441
TI  - Identification and quantification of neuropeptides in brain tissue by capillary
      liquid chromatography coupled off-line to MALDI-TOF and MALDI-TOF/TOF-MS.
AB  - Capillary liquid chromatography (CLC) coupled off-line with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF
      MS were explored for identification and quantification of neuropeptides in
      microwave-fixed rat brain tissue. Sample was separated by gradient elution on 50
      mum-inner diameter reversed-phase columns at 180 nL/min. Effluent was mixed with
      matrix solution and transferred to a MALDI target plate by pulsed electric field
      deposition, yielding sample spots with 200-300-mum diameter. Mass detection
      limits as low as 2 amol, corresponding to 1 pM concentration, were achieved for
      neuropeptides. CLC-MALDI-TOF-MS analysis of microwave-fixed rat striatum tissue
      yielded detection of over 400 distinctive peaks. CLC-MALDI-TOF/TOF-MS allowed
      identification of 10 peptides including 3 novel peptides. Quantification was
      evaluated using substance P as analyte and 15N3-labeled substance P as an
      internal standard. Quantification of substance P revealed approximately 6.8-fold
      higher levels than previously reported in the rat striatum. This increase is
      attributed to use of microwave fixation, which prevented degradation of the
      peptide, aggressive extraction procedures, and accounting for oxidation of
      substance P in the analysis. These results demonstrate that CLC-MALDI-TOF-MS is a
      versatile tool for neuropeptide analysis in brain tissue by allowing for
      detection, identification, and quantification.

PMID- 16808442
TI  - Ozone in ambient air as a source of adventitious oxidation. A mass spectrometric
      study.
AB  - This paper reports on an oxidation of biomolecules that can occur during sample
      preparation for analysis by matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS). In measurements performed over several years, the
      oxidation artifacts were detected on methionine and tryptophan side chains in
      peptides containing these residues, as well as at the carbon-carbon double bonds
      of unsaturated phospholipids. A distinct hallmark of the artifacts is their
      seasonal nature: the highest levels of oxidation are typically seen in samples
      prepared for MALDI analysis during daytime hours and warmer months. The artifacts
      appear strongest when samples are allowed to air-dry in the absence of MALDI
      matrix and can be minimized when sample preparation is carried out in a nitrogen
      atmosphere or under vacuum. It is proposed that ambient ozone (originating from
      outdoor air taken into the laboratory through the air handling system) is acting
      during the obligate MALDI sample dry-down and matrix crystallization steps. To
      confirm the hypothesis, ozonolysis experiments as well as direct measurements of
      ambient ozone levels were performed. The hypothesis is reminiscent of the recent
      finding that ozone is the source of degradation of self-assembled alkanethiol
      monolayers that are exposed to ambient air (Schoenfisch, M. H.; Pemberton, J. E.
      J. Am. Chem. Soc. 1998, 120, 4502-4513). Thus, caution should be taken in
      handling ozone-reactive substances that are placed thinly on surfaces and exposed
      to ambient air, whether for MALDI analysis or for other increasingly popular
      applications involving the microdeposition of liquids.

PMID- 16808443
TI  - Automated analysis of electrospray ionization fourier transform ion cyclotron
      resonance mass spectra of natural organic matter.
AB  - The advent of ultra-high-resolution mass spectrometry has revolutionized the
      ability of aquatic biogeochemists to examine molecular-level components of
      complex mixtures of organic matter. The ability to accurately assess the chemical
      composition, elemental formulas, or both of detected compounds is critical to
      these studies. Here we build on previous work that uses functional group
      relationships between compounds to extend elemental formulas of low molecular
      weight compounds to those of higher molecular weight. We propose an automated
      compound identification algorithm (CIA) for the analysis of ultra-high-resolution
      mass spectra of natural organic matter acquired by electrospray ionization
      Fourier transform ion cyclotron resonance mass spectrometry. This approach is
      benchmarked with synthetic data sets of compounds cited in the literature. The
      sensitivity of our results is examined for different sources of error, and CIA is
      applied to two previously published data sets. We find that CIA works well for
      data sets with high mass accuracy (<1 ppm) and can accurately determine the
      elemental formulas for >95% of all compounds composed of C, H, O, and N. Data
      with lower mass accuracy must be accompanied with additional knowledge of
      chemical structure, composition, or both in order to yield accurate elemental
      formulas.

PMID- 16808444
TI  - Probabilistic enrichment of phosphopeptides by their mass defect.
AB  - The mass defect, that is, the difference between the nominal and actual
      monoisotopic masses, of a phosphorus in a phosphate group is greater than for
      most other atoms present in proteins. When the mass defects of tryptic peptides
      derived from the human proteome are plotted against their masses, phosphopeptides
      tend to fall off the regression line. By calculating the masses of all potential
      tryptic peptides from the human proteome, we show that regions of higher
      phosphorylation probability exist on such a plot. We developed a transformation
      function to estimate the mass defect of a peptide from its monoisotopic mass and
      empirically defined a simple formula for a user-selectable discriminant line that
      categorizes a peptide mass according to its probability of being phosphorylated.
      Our method performs similarly well on phosphopeptides derived from a database of
      experimentally validated phosphoproteins. The method is relatively insensitive to
      mass measurement error of up to 20 ppm. The approach can be used with a tandem
      mass spectrometer in real time to rapidly select and rank order the possible
      phosphopeptides from a mixture of unmodified peptides for subsequent
      phosphorylation site mapping and peptide sequence analysis.

PMID- 16808445
TI  - Characterization of ac voltammetric reaction-diffusion dynamics: from patterns to
      physical parameters.
AB  - Despite the widespread use of electrochemical sensing techniques, the
      determination of the physical parameters from the current response of rapid
      voltammetric measurements has been difficult for two reasons: large capacitance
      contributions overwhelm the current response of transient measurements and the
      reaction dynamics are inherently nonlinear and nonstationary. In this work, we
      present a signal processing methodology that in combination with a large
      amplitude/high-frequency voltage waveform method, ac voltammetry, is able to
      determine the underlying physical parameters in heterogeneous electrochemical
      reaction-diffusion processes. Through a large number of numerical calculations,
      we explore the effect of kinetic, thermodynamic, and mass transport parameters on
      two components of the current response, the even and the odd. We study the even
      component directly whereas for the odd component, which is considerably
      influenced by capacitance, we use the Hilbert transform, which is suitable for
      the analysis of nonstationary and nonlinear data sets, to minimize the
      capacitance contribution. The theoretical analysis is applied to measurements of
      well-characterized electrochemical reactions, Ru(NH3)6(2+/3+) and Fe(CN)6(4-/3-),
      using two different electrode materials, glassy carbon and platinum, and the
      physical parameters deduced are in excellent agreement with published results.

PMID- 16808446
TI  - Tubulin-binding drug screening by MALDI-TOFMS.
AB  - Despite a large amount of drugs available to treat cancer, none is totally
      satisfactory with respect to its tolerance or side effects. It is very important
      to discover new compounds that exhibit specific features such as binding to
      proteic targets. Given the clinical successes of the poisons of the mitotic
      spindle chemotherapeutic agent class, it is often considered that tubulin
      represents one of the best cancer targets identified so far, and it seems likely
      that discovering new drugs of this class will significantly improve the range of
      active chemotherapeutic agents. The aim of this work is to present the new
      screening test that has been developed in our laboratory in order to study the
      binding of compounds to tubulin. We have developed a screening protocol involving
      three sampling strategies before the MALDI-TOFMS analysis. The three strategies
      give very accurate and reproducible results and could therefore possibly be used
      in screening campaigns. We have also proved that no unspecific binding can
      provide a loss of specificity of the test. Our protocol presents all the
      requirements for being a useful tool to screen the binding of compounds to
      tubulin.

PMID- 16808447
TI  - Statistical search space reduction and two-dimensional data display approaches
      for UPLC-MS in biomarker discovery and pathway analysis.
AB  - A new analytical strategy for biomarker recovery from directly coupled ultra
      performance liquid chromatography time-of-flight mass spectrometry (UPLC Tof MS)
      data on biofluids is presented and exemplified using a study on hydrazine-induced
      liver toxicity. A key step in the strategy involves a novel procedure for
      reducing the spectroscopic search space by differential analysis of cohorts of
      normal and pathological samples using an orthogonal projection to latent
      structures discriminant analysis (O-PLS-DA). This efficiently sorts principal
      discriminators of toxicity from the background of thousands of metabolic features
      commonly observed in data sets generated by UPLC-MS analysis of biological fluids
      and is thus a powerful tool for biomarker discovery.

PMID- 16808448
TI  - Self-associating block copolymer networks for microchip electrophoresis provide
      enhanced DNA separation via "inchworm" chain dynamics.
AB  - We describe a novel class of DNA separation media for microchip electrophoresis,
      "physically cross-linked" block copolymer networks, which provide rapid (<4.5
      min) and remarkably enhanced resolution of DNA in a size range critical for
      genotyping. Linear poly(acrylamide-co-dihexylacrylamide) (LPA-co-DHA) comprising
      as little as 0.13 mol % dihexylacrylamide yields substantially improved
      electrophoretic DNA separations compared to matched molar mass linear
      polyacrylamide. Single-molecule videomicroscopic images of DNA electrophoresis
      reveal novel chain dynamics in LPA-co-DHA matrixes, resembling inchworm movement,
      to which we attribute the increased DNA resolution. Substantial improvements in
      DNA peak separation are obtained, in particular, in LPA-co-DHA solutions at
      polymer/copolymer concentrations near the interchain entanglement threshold.
      Higher polymer concentrations yield enhanced separations only for small DNA
      molecules (<120 base pairs). Hydrophobically cross-linked networks offer
      advantages over conventional linear polymers based on enhanced separation
      performance (or speed) and over chemically cross-linked gels because hydrophobic
      cross-links can be reversibly broken, allowing facile microchannel loading.

PMID- 16808449
TI  - Improving the instrumental resolution of sensors based on localized surface
      plasmon resonance.
AB  - The colorimetric variations induced upon changes in interfacial refractive index
      of nanoscale noble metal structures exhibiting localized surface plasmon
      resonance (LSPR) provides a convenient means of label-free, affinity-based
      detection of biomolecular recognition reactions. However, despite being similar
      in nature to conventional SPR, LSPR has so far suffered from significantly lower
      data quality in terms of its signal-to-noise ratio (S/N) in typical biomolecular
      recognition analysis. In this work, generic data analysis algorithms and a simple
      experimental setup that provide a S/N upon protein binding that is comparable to
      that of state-of-the art SPR systems are presented. Specifically, it is
      demonstrated how temporal variations (rate approximately 0.5 Hz) in parameters
      proportional to the resonance peak position can be recorded simultaneously,
      yielding a peak position precision of <5 x 10(-4) nm and an extinction noise
      level of <5 x 10(-6) absorbance units (Abs). This, in turn, is shown to provide a
      S/N of approximately 2000 (equivalent to a detection limit of <0.1 ng/cm(2)) for
      typical protein binding reactions. Furthermore, the importance of utilizing
      changes in both peak position and magnitude is highlighted by comparing different
      LSPR active noble metal architectures that respond differently to bulk and
      interfacial refractive index changes.

PMID- 16808450
TI  - Studies on stress-induced changes at the subcellular level by Raman
      microspectroscopic mapping.
AB  - Raman microspectroscopic mapping enables one to study the chemical composition
      and molecular structure of subcellular components in individual cells without the
      need for labeling. Lung fibroblast cells were prepared under normal conditions
      and under stress, which was induced by 24 h of exposure to glyoxal. Raman
      microspectroscopic maps were recorded from fixed cells with 785-nm excitation and
      with 1-microm step width. Cluster analysis was applied to generate pseudocolor
      images of the cell morphology. Raman maps revealed that the cell nucleus shrinks
      in stressed cells, called pyknosis, which refers to an early stage of apoptosis.
      The intensity of nucleic acid bands decreased in cluster-averaged Raman spectra
      of the nucleus and cytoplasm, which is consistent with degradation and
      conformational changes of DNA and RNA. During a later stage of apoptosis, Raman
      maps indicate a rounding of cells, a further intensity decrease of nucleic acids
      bands, fragmentation of the nucleus, disappearance of lipid bodies, and formation
      of blisters at the cell surface. Whereas the peripheral membrane of the
      undisturbed cell is composed of lipids and cholesterol, the blisters have a
      higher protein content with nucleic acids incorporated. The results demonstrate
      that Raman spectroscopic mapping might become a powerful tool in cell biology for
      single cell analysis.

PMID- 16808451
TI  - Targeted profiling: quantitative analysis of 1H NMR metabolomics data.
AB  - Extracting meaningful information from complex spectroscopic data of metabolite
      mixtures is an area of active research in the emerging field of "metabolomics",
      which combines metabolism, spectroscopy, and multivariate statistical analysis
      (pattern recognition) methods. Chemometric analysis and comparison of 1H NMR1
      spectra is commonly hampered by intersample peak position and line width
      variation due to matrix effects (pH, ionic strength, etc.). Here a novel method
      for mixture analysis is presented, defined as "targeted profiling". Individual
      NMR resonances of interest are mathematically modeled from pure compound spectra.
      This database is then interrogated to identify and quantify metabolites in
      complex spectra of mixtures, such as biofluids. The technique is validated
      against a traditional "spectral binning" analysis on the basis of sensitivity to
      water suppression (presaturation, NOESY-presaturation, WET, and CPMG), relaxation
      effects, and NMR spectral acquisition times (3, 4, 5, and 6 s/scan) using PCA
      pattern recognition analysis. In addition, a quantitative validation is performed
      against various metabolites at physiological concentrations (9 microM-8 mM).
      "Targeted profiling" is highly stable in PCA-based pattern recognition,
      insensitive to water suppression, relaxation times (within the ranges examined),
      and scaling factors; hence, direct comparison of data acquired under varying
      conditions is made possible. In particular, analysis of metabolites at low
      concentration and overlapping regions are well suited to this analysis. We
      discuss how targeted profiling can be applied for mixture analysis and examine
      the effect of various acquisition parameters on the accuracy of quantification.

PMID- 16808452
TI  - Correlation between protein binding strength on immobilized metal affinity
      chromatography and the histidine-related protein surface structure.
AB  - Immobilized metal affinity chromatography (IMAC) was investigated for its ability
      to characterize the histidine-related surface structure of a protein, that is, a
      histidine residue's surface accessibility and its potential involvement in
      intramolecular interactions. T4 lysozyme was chosen as the model protein. Seven
      amino acid sites were selected on the basis of their relative surface
      accessibility, and they were substituted with histidine via site-directed protein
      mutagenesis to generate seven T4 lysozyme variants, each containing only one
      histidine residue on its surface, with various surface accessibility. IMAC was
      then used to experimentally quantify the interaction of each lysozyme variant
      with immobilized copper ions. A direct correlation was shown between the protein
      binding affinity and the surface accessibility of the histidine residue. Of all
      the lysozyme variants, K83H and K147H showed unusually low binding strength, as
      compared with variants having a histidine residue with a similar surface
      accessibility. However, with the aid of molecular modeling, their relatively low
      binding affinities were predicted to be the result of the involvement of the
      histidine residue in intramolecular interactions. In contrast to previously
      reported results, our results showed that lysozyme still binds to the IMAC
      column, even if its histidine residue is involved in intramolecular bonding, such
      as a hydrogen bond, albeit at reduced strength, as compared with the variant
      containing a histidine residue with a similar surface accessibility.

PMID- 16808453
TI  - Magnetically-assisted transport evanescent field fluoroimmunoassay.
AB  - The immunoassay, based on specific recognition of an antigen by its antibody, has
      garnered widespread use in clinical analysis as well as application in such areas
      as food industry and environmental monitoring. Fluoroimmunoassays (FIAs) are
      especially attractive due to the inherent sensitivity of fluorescence
      spectroscopy and the availability of a wide range of commercial antibodies and
      fluorescent labels. In current form, however, FIAs can be cumbersome, multistep
      procedures and often lack versatility when there is interest in measuring many
      different target antigens. This report is proof of a concept paper introducing a
      new FIA approach, Magnetically-Assisted Transport Evanescent Field
      Fluoroimmunoassays (MATEFFs), which seeks to preserve the advantages of current
      approaches to FIAs while attempting to address some of the drawbacks. MATEFFs
      utilize magnetic microspheres as solid supports for the fluoroimmunoassay with
      direct detection of bound analyte within the sample mixture effected by
      selectively driving the functionalized beads to a prism surface using an external
      magnet. An evanescent wave is generated by total internal reflection of a laser
      beam at the optical interface between the prism and sample and serves to excite
      the fluorescent species magnetically delivered into the localized field. This
      technique eliminates wash steps without compromising sensitivity, all the while
      minimizing interference from fluorescing species present in the sample matrix.
      Preliminary optimization studies assessing the impact of background interfering
      agents, incident angle, magnetic field direction, laser power density via
      focusing, and bead concentration on MATEFFs performance characteristics are
      discussed herein along with a detailed description of the experimental platform.
      Utilizing a model sandwich assay system with biotinylated anti-IgG as the capture
      antibody, rabbit IgG as the antigen, and anti-IgG-R-phycoerythrin as the reporter
      antibody, we demonstrate a linear dynamic range of 3 orders of magnitude,
      physiologically relevant detection limits of low nanograms per milliliter, and
      RSD values of less than 5%.

PMID- 16808454
TI  - PCR-free DNA detection using a magnetic bead-supported polymeric transducer and
      microelectromagnetic traps.
AB  - A fluorescent polymeric hybridization transducer supported on magnetic microbeads
      was investigated for the rapid, ultrasensitive, and sequence-specific detection
      of DNA. We show that the polymer derivative can be used to detect target DNA
      directly on magnetic particles by preparing "target-ready" microbeads grafted
      with the polymer and suitable DNA probes. A detection limit of approximately 200
      target copies in a probed volume of 150 muL (1.4 copies/muL) was obtained for a
      DNA sequence specific to Candida albicans This detection scheme does not require
      the release of the hybridized target DNA prior to its detection or the labeling
      or amplification of the nucleic acids. Furthermore, we show that the fluorescence
      from these biosensing magnetic beads can be read while magnetically confined in a
      small volume by a microelectromagnetic trap, which offers the possibility of
      performing both the preconcentration and detection steps simultaneously on the
      same support. The combination of the fluorescent polymer biosensor with magnetic
      particle-assisted DNA preconcentration extends the application of this
      ultrasensitive biosensor to biological samples with complex matrixes and to
      integrated lab-on-a-chip platforms, where it could be used for fast multitarget
      DNA detection in point-of-care diagnostics and field analysis.

PMID- 16808455
TI  - Achieving uniform mixing in a microfluidic device: hydrodynamic focusing prior to
      mixing.
AB  - We describe a microfluidic mixer that is well-suited for kinetic studies of
      macromolecular conformational change under a broad range of experimental
      conditions. The mixer exploits hydrodynamic focusing to create a thin jet
      containing the macromolecules of interest. Kinetic reactions are triggered by
      molecular diffusion into the jet from adjacent flow layers. The ultimate time
      resolution of these devices can be restricted by premature contact between co
      flowing solutions during the focusing process. Here, we describe the design and
      characterization of a mixer in which hydrodynamic focusing is decoupled from the
      diffusion of reactants, so that the focusing region is free from undesirable
      contact between the reactants. Uniform mixing on the microsecond time scale is
      demonstrated using a device fabricated by imprinting optical-grade plastic.
      Device characterization is carried out using fluorescence correlation
      spectroscopy (FCS) and two-photon microscopy to measure flow speeds and to
      quantify diffusive mixing by monitoring the collisional fluorescence quenching,
      respectively. Criteria for achieving microsecond time resolution are described
      and modeled.

PMID- 16808456
TI  - Hadamard transform ion mobility spectrometry.
AB  - A detection scheme that makes use of the Hadamard transform has been employed
      with an atmospheric-pressure ion mobility spectrometer fitted with an
      electrospray ionization source. The Hadamard transform was implemented through
      the use of a linear-feedback shift register to produce a pseudorandom sequence of
      1023 points. This pseudorandom sequence was applied to the ion gate of the
      spectrometer, and deconvolution of the ion signal was accomplished by the
      Hadamard transform to reconstruct the mobility spectrum. Ion mobility spectra
      were collected in both a conventional and Hadamard mode, with comparisons made
      between the two approaches. Initial results exhibited low spectral definition, so
      an oversampling technique was applied to increase the number of data points
      across each analyte spectral peak. The use of the Hadamard transform increases
      the duty cycle of the instrument to 50% and results in a roughly 5-fold
      enhancement of the signal-to-noise ratio with a negligible loss of instrument
      resolution. It is also shown that any potential multiplex disadvantage, which
      limits the attractiveness of some high-throughput techniques, is not a limiting
      factor in this new implementation.

PMID- 16808457
TI  - Enzyme system for improving the detection limit in pyrosequencing.
AB  - Highly sensitive real-time pyrosequencing seems promising for constructing an
      inexpensive and small DNA sequencer with a low running cost. A DNA sample of a
      picomole level is usually used in the conventional pyrosequencing based on a
      luciferase assay coupled with an APS-ATP surfurylase reaction for producing ATP
      from pyrophosphate (PPi). Although the luminescence intensity could be increased
      by increasing the amount of luciferase, it was impossible to reduce the target
      DNA amount because of a large background luminescence due to the luciferase-APS
      reaction. In this report, a novel approach using a new conversion reaction of PPi
      to ATP is proposed. This method has a very low background and can produce high
      signals in the presence of a large amount of luciferase; thus, the sample amount
      required for sequencing is significantly reduced. The ATP production from PPi is
      catalyzed with pyruvate orthophosphate dikinase (PPDK) using AMP and
      phosphoenolpyruvate as the substrates, which are inactive for the luciferase
      catalyzed reaction. All of the components in the AMP-PPDK-based pyrosequencing
      system are suitable for highly sensitive DNA sequencing in one tube. Real-time
      DNA sequencing with a readable length up to 70 bases was successfully
      demonstrated by using this system. By increasing the amount of luciferase, as low
      as 2.5 fmol of DNA templates was accurately sequenced by the proposed method with
      a novel simple and inexpensive DNA sequencer having a photodiode array as a
      sensor instead of a PMT or CCD camera. A sample amount as low as 2 orders of
      magnitude smaller than that used in the conventional pyrosequencer can be used.

PMID- 16808458
TI  - Combined GC/MS analytical procedure for the characterization of glycerolipid,
      waxy, resinous, and proteinaceous materials in a unique paint microsample.
AB  - A novel GC/MS analytical procedure for the identification of lipids, waxes,
      proteins, and resinous materials in the same microsample from painted works of
      art has been optimized. It is based on a sample multistep chemical pretreatment
      (solvent extractions and microwave-assisted chemolysis) that is able to separate
      the various organic components into different fractions, which are suitably
      treated and derivatized before analysis. In particular, the procedure allows the
      complete saponification of wax esters and the completeness of the Cannizzaro type
      reaction of shellac acids in conditions that are suitable also for glycerides
      saponification. The method was tested on reference materials for the
      identification of proteinaceous binders (egg, collagen, casein) on the basis of
      the quantitative determination of the amino acid profile and the identification
      of glycerolipids (linseed oil, poppy seed oil, walnut oil, and egg), plant resins
      (Pinaceae resins, sandarac, mastic, and dammar), animal resins (shellac), tars or
      pitches, and natural waxes (beeswax, carnauba wax) on the basis of the
      determination of fatty acid, alcohol, and hydrocarbon profiles and of significant
      terpenic molecular markers. The procedure was applied to the characterization of
      three old paint microsamples. Animal glue, egg, linseed oil, beeswax, Pinaceae
      resin, dammar, and shellac were the identified materials found in mixtures and
      recognized as original and/or restoration substances.

PMID- 16808459
TI  - Isolation and characterization of a thermally stable recombinant anti-caffeine
      heavy-chain antibody fragment.
AB  - We have isolated and characterized a caffeine-specific, heavy-chain-only antibody
      fragment (V(HH)) from llama that is capable of being utilized to analyze caffeine
      in hot and cold beverages. Camelid species (llama and camel) were selected for
      immunization because of their potential to make heat-stable, heavy-chain-only
      antibodies. Llamas and camels were immunized with caffeine covalently linked to
      keyhole limpet hemocyanin, and recombinant antibody techniques were used to
      create phage displayed libraries of variable region fragments of the heavy-chain
      antibodies. Caffeine-specific V(HH) fragments were selected by their ability to
      bind to caffeine/bovine serum albumin (BSA) and confirmed by a positive reaction
      in a caffeine enzyme-linked immunosorbent assay (caffeine ELISA). One of these
      V(HH) fragments (VSA2) was expressed as a soluble protein and shown to recover
      its reactivity after exposure to temperatures up to 90 degrees C. In addition,
      VSA2 was able to bind caffeine at 70 degrees C. A competition caffeine ELISA was
      developed for the measurement of caffeine in beverages, and concentrations of
      caffeine obtained for coffee, Coca-Cola Classic, and Diet Coke agreed well with
      high performance liquid chromatography (HPLC) determination and literature
      values. VSA2 showed minimal cross reactivity with structurally related
      methylxanthines.

PMID- 16808460
TI  - Analysis of the gas phase of cigarette smoke by gas chromatography coupled with
      UV-diode array detection.
AB  - A gas chromatography method, coupled with diode array photometric spectral
      detection in the ultraviolet region (167-330 nm), was developed for the analysis
      of the gas phase of cigarette smoke. The method enabled us to identify more than
      20 volatiles present in the vapor phase of cigarette smoke. In that way, all
      major volatile organic compounds (including aldehydes, conjugated dienes,
      ketones, sulfides, furans, and single-ring aromatics), as well as nitric oxide
      (NO) and hydrogen sulfide (H(2)S), can be analyzed in a straightforward manner
      through a single chromatographic run of <50-min duration. The method can easily
      be applied by the introduction of a small volume of the gas-phase stream into the
      GC injection loop directly through the smoking apparatus exhaust circuit, thus
      providing an excellent alternative to available methods, which usually require
      extraction or concentration steps prior to any chromatographic analysis.
      Furthermore, all problems concerning aging of the gas phase are eliminated.
      Twelve compounds (including NO) were chosen for quantification through the use of
      appropriate calibration standards. Comparison of the vapor phase yields of these
      compounds for the reference cigarette Kentucky 1R4F with already reported data
      indicates that this method is very reliable as far as accuracy and
      reproducibility of the results are concerned. Finally, the proposed methodology
      was used to compare the concentration of these cigarette smoke gas-phase
      constituents among individual puffs.

PMID- 16808461
TI  - Isothermal calorimetry as a tool to investigate slow conformational changes in
      proteins and peptides.
AB  - A new calorimetric method has been developed to follow the time course of slow
      conformational changes during the refolding of denatured proteins. The method is
      based on the ability of isothermal titration calorimeters (ITC) to detect small
      amounts of heat continuously over a minute to an hour time range without being
      disturbed by baseline drift. We benchmarked the method on the basis of the slow
      kinetic phases resulting from prolyl cis/trans isomerization of oligopeptides.
      Using this method, the simultaneous investigation of the kinetics and
      thermodynamics of slow phases in the refolding of GdmCl-denatured RNase A by
      single jump techniques was performed. Time traces of heat production in the
      presence of a peptidyl prolyl cis/trans isomerase support the classical model of
      rate-limiting prolyl trans to cis isomerizations in the folding reactions of
      RNase A. However, we also observed that, unlike prolyl cis/trans isomerizations
      in oligopeptides, those found in RNase A refolding are highly exothermic. It
      appears that coupling between slow prolyl trans to cis isomerization and
      relocation of remote backbone segments increases the number of contacting sites
      during formation of the native protein. The results demonstrate that
      calorimetrically monitored folding kinetics will be of relevance in the detection
      of otherwise silent folding events.

PMID- 16808462
TI  - Binding of small mono- and oligomeric integrin ligands to membrane-embedded
      integrins monitored by surface plasmon-enhanced fluorescence spectroscopy.
AB  - We recently developed a binding assay format by incorporating native
      transmembrane receptors into artificial phospholipid bilayers on biosensor
      devices for surface plasmon resonance spectroscopy. By extending the method to
      surface plasmon-enhanced fluorescence spectroscopy (SPFS), sensitive recording of
      the association of even very small ligands is enabled. Herewith, we monitored
      binding of synthetic mono- and oligomeric RGD-based peptides and peptidomimetics
      to integrins alphavbeta3 and alphavbeta5, after having confirmed correct
      orientation and functionality of membrane-embedded integrins. We evaluated
      integrin binding of RGD multimers linked together via aminohexanoic acid (Ahx)
      spacers and showed that the dimer revealed higher binding activity than the
      tetramer, followed by the RGD monomers. The peptidomimetic was also found to be
      highly active with a slightly higher selectivity toward alphavbeta3. The
      different compounds were also evaluated in in vitro cell adhesion tests for their
      capacity to interfere with alphavbeta3-mediated cell attachment to vitronectin.
      We hereby demonstrated that the different RGD monomers were similarly effective;
      the RGD dimer and tetramer showed comparable IC50 values, which were, however,
      significantly higher than those of the monomers. Best cell detachment from
      vitronectin was achieved by the peptidomimetic. The novel SPFS-binding assay
      platform proves to be a suitable, reliable, and sensitive method to monitor the
      binding capacity of small ligands to native transmembrane receptors, here
      demonstrated for integrins.

PMID- 16808463
TI  - Characterization of sulfated oligosaccharides in mucopolysaccharidosis type IIIA
      by electrospray ionization mass spectrometry.
AB  - Heparan sulfate is a linear glycosaminoglycan with considerable structural
      diversity that binds a myriad of growth factors and proteins that play pivotal
      roles in a variety of biological processes. We have investigated the structural
      complexity of partially degraded fragments of heparan sulfate in
      mucopolysaccharidosis type IIIA in which there is a defect in heparan sulfate
      catabolism. Mono- to hexadecasaccharides were isolated from the urine of a
      mucopolysaccharidosis IIIA patient and shown to have non-reducing end glucosamine
      N-sulfate residues, reflecting the catabolic deficiency in heparan N-sulfatase
      (sulfamidase) activity. The use of nitrous acid digestion (pH 1.5) combined with
      separation by reverse-phase high-performance liquid chromatography and analysis
      by electrospray ionization-mass spectrometry identified multiple forms of these
      oligosaccharides with some N-acetylated glucosamine residues and one to three
      sulfates per disaccharide. Furthermore, we demonstrated that each oligosaccharide
      existed in multiple sulfated forms. Many structural isomers were present,
      suggesting a complex mixture of oligosaccharides present in the urine as a
      consequence of a defect in heparan sulfate degradation.

PMID- 16808464
TI  - Utility of cleavable isotope-coded affinity-tagged reagents for quantification of
      low-copy proteins induced by methylprednisolone using liquid
      chromatography/tandem mass spectrometry.
AB  - Gene expression changes underlie important biological and pharmacological
      responses. Although mRNA expression profiling is routine, quantification of low
      abundance proteins, which typically represent key effectors of responses, remains
      challenging. A novel strategy was developed for sensitive and accurate
      quantification of low-abundance proteins in highly complex biological matrixes.
      First, the cysteine specificity of cleavable isotope-coded affinity tags (cICAT)
      was employed to reduce the complexity of the digested proteome of tissue
      homogenates and to improve the quantification of low-abundance proteins. Second,
      cICAT-treated tissue samples were analyzed on a capillary LC coupled to an ion
      trap MS to screen for the subset of cICAT-peptides, derived from target proteins
      of interest, that was successfully labeled and retrieved. Third, putatively
      identified peptides derived from target proteins were synthesized, cICAT-labeled,
      and used both to optimize multiple reactions monitoring (MRM) analysis and to
      confirm chromatographic retention time and fragmentation pattern. Finally, batch
      quantification of target peptides was performed using MRM on a LC/triple-quad
      MS/MS using (12)C- (control) and (13)C (experimental)-cICAT-labeled tissue
      mixtures. The utility of this method was demonstrated by elucidating the time
      course of tyrosine aminotransferase induction in the liver of rats following
      treatment with the corticosteroid methylprednisolone (MPL). This approach
      significantly improved quantitative sensitivity, and the linear range was 10-fold
      greater than published previously. An additional advantage is that archived
      samples may be reinterrogated to investigate the regulation of additional targets
      that become of interest. Stored samples were sucessfully reinterrogated to
      monitor the induction of ornithine decarboxylase, which is also an MPL-induced
      protein. To our knowledge, this is the first report of an ICAT-based method that
      is capable of quantifying low-abundance proteins in highly complex samples, such
      as tissue homogenates. The approach enables simultaneous quantification of
      multiple effector proteins induced by biological or pharmacological stimuli, and
      the processed samples can be interrogated repeatedly as additional targets of
      interest arise.

PMID- 16808465
TI  - Miniature differential mobility spectrometry using atmospheric pressure
      photoionization.
AB  - Positive and negative ion spectra have been obtained with a miniature
      differential mobility spectrometer equipped with a photoionization source
      operating at atmospheric pressure. With benzene as a dopant, providing C6H6+ as
      reactant ion, protonated molecular ions and proton-bound dimer ions were obtained
      with dimethyl methylphosphonate and butanone. The spectra obtained from gas
      chromatographic injections of aromatic hydrocarbons, benzene, toluene, and the
      xylenes, produced the molecular ions when the moisture level was very low, but at
      a high level the hydrated proton was also present. Possible mechanisms for the
      formation of protonated products are discussed. Negative ions were produced from
      electron capture by sulfur hexafluoride using benzene or acetone as dopant.
      Photoionization of nitrogen dioxide led to the formation of the nitrate ion whose
      yield was a nonlinear function of concentration. The use of a suitable dopant
      enhanced ion formation by up to 2 orders of magnitude, and limits of detection in
      both the positive and negative modes were all at the sub ppm(v) level. The study
      makes a strong case for the use of a photoionization source as an alternative to
      the radioactive 63Ni source.

PMID- 16808466
TI  - Metabolic profiling of glucuronides in human urine by LC-MS/MS and partial least
      squares discriminant analysis for classification and prediction of gender.
AB  - Mass spectrometry (MS) is increasingly being used for metabolic profiling, but
      detection modes such as constant neutral loss or multiple reaction monitoring
      have not often been reported. These modes allow focusing on structurally related
      compounds, which could be advantageous for situations in which the trait under
      investigation is associated with a particular class of metabolites. In this
      study, we analyzed endogenous glucuronides excreted in human urine by monitoring
      characteristic transitions of putative steroid glucuronides by LC-MS/MS for
      discrimination of females from males. Two methods for data extraction were used:
      (i) a manual procedure based on visual inspection of the chromatograms and
      selection of 23 peaks and (ii) a software-supported method (MarkerView) set to
      extract 100 peaks. Data from 10 female and 10 male students were analyzed by
      principal component analysis (PCA) and partial least-squares discriminant
      analysis (PLS-DA) using software SIMCA. With PCA, only the manual peak selection
      resulted in clustering males and females. With PLS-DA, the manual method provided
      full separation on the basis of one single discriminant; the software-supported
      approach required a two-component model for complete separation. Loading plots
      were analyzed for their ability to reveal peaks with high discriminating power,
      that is, potential biomarkers. The PLS-DA models were validated with urine
      samples collected from five new females and five new males. Gender was correctly
      assigned for all. Our results indicate that inclusion of biological criteria for
      variable selection coupled to class-specific MS analysis and data extraction by
      appropriate software may constitute a valuable addition to the methods available
      for metabolomics.

PMID- 16808467
TI  - Infrared multiphoton dissociation in quadrupole time-of-flight mass spectrometry:
      top-down characterization of proteins.
AB  - The first implementation of infrared multiphoton dissociation (IRMPD) for a
      hybrid quadrupole time-of-flight (QqTOF) mass spectrometer is reported. Ions were
      trapped in the radio frequency-only quadrupole (q2), which normally serves as a
      collision cell, and irradiated by a continuous CO2 IR laser. The laser beam was
      introduced coaxially with the quadrupoles in order to maximize overlap with the
      ion path. The resolution of the TOF mass analyzer allowed direct charge state
      determination for fragments smaller than 7 kDa. For larger fragments, the charge
      state could be assigned using the multiple losses of water, characteristic for
      IRMPD of proteins. The analytical performance is demonstrated by top-down
      sequencing of several representative proteins (equine myoglobin, bovine casein,
      and human insulin and chaperonin 10). Various post-translational modifications
      such as phosphorylation, acetylation, formation of disulfide bridges, and removal
      of N-terminal methionine followed by acetylation are detected and characterized.
      The utility of IRMPD for the analysis of biological samples is demonstrated in a
      study of a recently identified potential marker for endometrial cancer,
      chaperonin 10.

PMID- 16808468
TI  - Modulation ratio in comprehensive two-dimensional gas chromatography.
AB  - Comprehensive two-dimensional chromatography employs a serially coupled two
      column arrangement where effluent from the first column is collected or sampled
      and then introduced to the second column according to a chosen modulation period.
      This is effected by use of a modulator at or near the column junction. One of the
      considerations in applying the technique is the period of the modulator, which
      determines the sampling duration of the first column effluent. Here, we propose
      that the sampling rate can be most effectively described by a new term, called
      the modulation ratio (MR). This is defined as the ratio of 4 times the first
      column peak standard deviation (4sigma) divided by the modulation period (PM) or
      1.6985 times the half-height width of the peak (wh): MR = 4sigma/PM = wb/PM = (wh
      x 1.6985)/PM. The 4sigma value is more commonly recognized as the peak base width
      (wb). The use of 4sigma as the numerator is preferred to simply sigma because
      when the PM value used for an experiment is equal to sigma, then the MR value is
      calculated to be 4, implying that the primary peak will be modulated
      approximately 4 times as is normally recommended for a comprehensive
      multidimensional separation. The less well-defined term of modulation number (NM)
      has been previously used and proposed as the number of modulations per peak and,
      therefore, is intended to convey the manner in which the primary column peak is
      sampled; this is a subjective and not well-characterized value. The use of MR
      should provide users with a meaningful and strictly defined value when reporting
      experimental conditions. The utility of MR is demonstrated through a mathematical
      model of the modulation process for both Gaussian and tailing peaks, supported by
      an experimental study of the modulation ratio. It is shown that for the analysis
      of trace compounds where precise quantitative measurements are being made, the
      experiment should be conducted with an MR of at least 3. Conversely, for
      semiquantitative methods or the analysis of major components, an MR of
      approximately 1.5 should suffice.

PMID- 16808469
TI  - Controlling electroosmotic flow in poly(dimethylsiloxane) separation channels by
      means of prepolymer additives.
AB  - The electroosmotic flow (EOF) in a poly(dimethylsiloxane) (PDMS) separation
      channel can be altered and controlled by adding a carboxylic acid to the
      prepolymer prior to curing. When the prepolymer is doped with 0.5 wt %
      undecylenic acid (UDA), the electroosmotic mobility in a modified PDMS channel
      rises to (7.6 +/- 0.2) x 10(-4) cm(2) V(-1) s(-1) (in HEPES buffer at pH 8.5),
      which is nearly twice that in the native PDMS channel. Because this modification
      does not significantly change the hydrophobicity of the PDMS surface, it is
      possible to combine the modified PDMS with a dynamic coating of n-dodecyl beta-d
      maltoside (DDM), which prevents protein sticking (see Huang, B.; Wu, H. K.; Kim,
      S.; Zare, R. N. Lab Chip 2005, 5, 1005-1007). The modified PDMS channel with a
      dynamic coating of DDM generates an electroosmotic mobility of (5.01 +/- 0.09) x
      10(-4) cm(2) V(-1) s(-1), which shows excellent reproducibility both in
      successive runs and during storage in water. Combining this surface modification
      and the dynamic coating of DDM is an effective means for both providing stable
      EOF in the PDMS channels and preventing protein adsorption on the channel walls.
      To demonstrate these effects, we show that the electrophoretic separation of
      immunocomplexes in free solution can be readily accomplished in a microfluidic
      chip made of UDA-doped (0.5 wt %) PDMS with a dynamic coating of DDM.

PMID- 16808470
TI  - Establishment of long-term preservation for dimethyl sulfide by the solid-phase
      microextraction method.
AB  - Dimethyl sulfide (DMS) derived from marine biological activity affects radiative
      forcing of the climate. The general analytical technique for DMS in seawater
      (purge and trap analytical method, P&T) is complex onboard ship. Thus it is
      difficult to obtain sufficient data for a comprehensive understanding of the
      spatiotemporal variability of DMS in the sea surface layer. On the other hand, a
      new analytical method for DMS using SPME (solid-phase microextraction) has
      recently been developed as an alternative method to P&T. This method is simpler
      than P&T because no special or complex apparatus is needed. If it is possible to
      preserve DMS for an extended period in excess of the duration of the cruise, the
      SPME method is a promising method for measuring DMS in seawater. We assessed an
      analytical method which can allow us to preserve DMS on the long-term scale using
      SPME. In liquid nitrogen (-196 degrees C), as preserved environment, for a period
      of 20 days after sampling, we found the preservation rate of DMS to be 94.7 +/-
      4.4% (n = 6) in this study. Furthermore, estimating the distribution coefficient
      with respect to the effect of salinity on SPME, we found that DMS changed by 0.1
      nM/% sal, suggesting that salinity has only a minor influence on oceanic DMS
      measurements in the open ocean because the minimal change of the open ocean
      salinity is within 2 %. Applying the SPME method to open ocean samples, we found
      that there were no significant differences in DMS between the unpreserved and
      preserved samples (r = 0.99, n = 26, SE = 0.01, p < 0.0001), showing the SPME
      method has potential for use for open ocean surveys.

PMID- 16808471
TI  - Automatic selection of optimal Savitzky-Golay smoothing.
AB  - A method to select the optimal window size of the Savitzky-Golay (SG) algorithm
      is presented. The approach is based on a comparison of the fitting residuals
      (i.e., the differences between the input signal and the smoothed signal) with the
      noise of the instrument. The window size that yields an autocorrelation of the
      residuals closest to the autocorrelation of the noise of the instrument is
      considered optimal. The method is applied in two steps. In a first step, the lag
      one autocorrelation value of the noise of the instrument is computed through the
      study of a blank signal. In a second step, the SG algorithm is applied to
      "smooth" the signal using different window sizes. The method was applied to data
      from NMR, chromatography, and mass spectrometry and was shown to be robust. It
      finds the optimal window size for different signal features. This allows the
      method to be used in an unsupervised way, embedded in a more complex algorithm in
      which smoothing and/or differentiation of signals is required, provided that the
      lag-one autocorrelation value of the instrument noise does not change.

PMID- 16808472
TI  - Thermally assisted collision-induced dissociation in a quadrupole ion trap mass
      spectrometer.
AB  - Thermally assisted collision-induced dissociation (TA-CID) provides increased
      dissociation in comparison with CID performed at ambient temperature in a
      quadrupole ion trap mass spectrometer. Heating the bath/collision gas during CID
      increases the initial internal energy of the ions and reduces the collisional
      cooling rate. Thus, using the same CID parameters, the parent ion can be
      activated to higher levels of internal energy, increasing the efficiency of
      dissociation and the number of dissociation pathways. The increase in the number
      of dissociation pathways can provide additional structural information. A
      consequence of the increase in initial internal energy is the ability to use less
      power to effect collisional activation. This allows lower q(z) values to be used
      and, thus, a greater mass range of product ions to be observed. TA-CID alleviates
      the problems associated with traditional CID and results in more available
      information than traditional CID.

PMID- 16808473
TI  - Validation of the tracer-pulse method for multicomponent liquid chromatography, a
      classical paradox revisited.
AB  - The tracer-pulse method was extended and validated for the determination of
      multicomponent adsorption isotherms in liquid chromatography. Competitive
      adsorption isotherms can be determined for any number of solutes, up to the
      column resolution limit. The basic principle is to equilibrate the column with an
      eluent containing a mixture of the solutes and then measure the migration
      velocity of each of them through the column. It is easy to calculate the
      stationary phase concentrations from these velocities, given the eluent
      composition. As in frontal analysis, real competitive isotherm data are measured
      using this method, unlike other methods, which only produce parametric estimates.
      The method was used to measure the binary isotherms of beta-blockers on a
      Kromasil C8 column. The data were fitted to competitive bi-Langmuir adsorption
      isotherm functions and was found to agree well with the results of frontal
      analysis and the perturbation method. Computer simulations based on the isotherm
      parameters were performed and displayed very good agreement with the experimental
      chromatograms. An intriguing and seemingly paradoxical property is visualized and
      discussed: the fact that the injected molecules are not found in the detected
      peaks.

PMID- 16808474
TI  - LC-MS/MS screen for penitrem A and roquefortine C in serum and urine samples.
AB  - A rapid LC-MS/MS method, using a triple quadrupole/linear ion trap mass
      spectrometer, was developed for determination of penitrem A and roquefortine C in
      serum and urine samples. Penitrem A and roquefortine C were extracted from
      samples with methylene chloride. The extracts were injected onto a liquid
      chromatograph coupled with a hybrid triple quadrupole/linear ion trap mass
      spectrometer. Seven replicate fortifications of serum at 0.001 microg/g (1 ppb)
      each of penitrem A and roquefortine C gave average recoveries of 90% with 10% CV
      (relative standard deviation) and 97% with 3% CV, respectively. Seven replicate
      fortifications of urine at 0.001 microg/g (1 ppb) each of penitrem A and
      roquefortine C gave average recoveries of 98% with 12% CV and 100% with 6% CV,
      respectively. This is the first report of a positive mass spectrometric
      identification and quantitation of both compounds in urine and serum samples from
      dog intoxication cases.

PMID- 16808475
TI  - Use of elemental analysis to determine comparative performance of established DNA
      quantification methods.
AB  - Quantification of genomic DNA is critical for many analyses in molecular biology.
      Current methods include optical density (OD) measurements or fluorescent
      enhancement but both approaches have limitations on achievable accuracy. In this
      study we performed an elemental analysis to quantify genomic DNA to provide an
      independent value for comparing the performance of four quantification methods.
      Specifically ICP-OES (inductively coupled plasma-optical emission spectroscopy)
      was used to assign a concentration value to a DNA stock solution, based on the
      stoichiometry of phosphorus within the molecule. Two absorbance- and two
      fluorescence-based methods were then used to quantify the same DNA solution using
      replicate analyses. The precision of each method was assessed by measurement of
      replicate spread (coefficient of variation) and trueness by t-test. Results
      showed that performance of the methods was variable, both in terms of concordance
      with the independent ICP-OES value and repeatability of data. While need for
      expensive equipment and technical expertise may preclude widespread replacement
      of more traditional methods for DNA quantification, use of primary methods such
      as ICP-OES analysis for production of accurate calibrants may increase
      quantitative accuracy and give greater appreciation of the true performance of
      current methods.

PMID- 16808476
TI  - Chemical characterization of diaspirin cross-linked hemoglobin polymerized with
      poly(ethylene glycol).
AB  - A lack of specificity associated with chemical modification methods used in the
      preparation of certain hemoglobin (Hb)-based oxygen carriers (HBOCs) may alter Hb
      structure and function, as amino acids located in critical regions (e.g., alpha
      beta interfaces and the 2,3-DPG binding pocket) may unintentionally be targeted.
      Hb protein surface modifications with various poly(ethylene glycol) (PEG)
      derivatives have been used as conjugating and polymerizing agents with the intent
      of improving reaction site specificity/reproducibility and ultimately reducing
      the untoward hypertensive response due to nitric oxide scavenging by smaller
      molecular size tetrameric species (i.e., 64 kDa) in HBOC solutions. Previous
      experiments performed in our laboratory have evaluated the influence of
      polymerization of diaspirin alpha-alpha cross-linked Hb (alphaalpha-DBBF-Hb) with
      a bifunctional modified PEG, bis(maleoylglycylamide) PEG (BMAA-PEG), in terms of
      oxygen carrying capacity, redox properties, hypertensive response, and renal
      clearance in rats. The data presented in this paper specifically evaluate the
      influence of BMAA-PEG on alphaalpha-DBBF-Hb (Poly-alphaalpha-DBBF-Hb) to identify
      molecular weight distribution, protein conformation, and site-specific
      modification, as well as to provide insight into the previously determined in
      vitro and in vivo functional and vasoactive characteristics of this HBOC.
      Chemical analysis performed herein reveals nonspecific modifications induced by
      BMAA-PEG that result in the full modification of alphaalpha-DBBF-Hb leaving no
      tetrameric cross-linked starting material in solution. These data are
      inconsistent with the continuing assumption that molecular size (i.e., 64 kDa)
      has a direct influence on HBOC-mediated vasoactivity and that other protective
      strategies should be considered to control blood pressure imbalances.

PMID- 16808477
TI  - Adsorption mechanisms and effect of temperature in reversed-phase liquid
      chromatography. meaning of the classical Van't Hoff plot in chromatography.
AB  - The effect of temperature on the adsorption and retention behaviors of a low
      molecular weight compound (phenol) on a C18-bonded silica column (C18-Sunfire,
      Waters) from aqueous solutions of methanol (20%) or acetonitrile (15%) was
      investigated. The results of the measurements were interpreted successively on
      the basis of the linear (i.e., overall retention factors) and the nonlinear
      (i.e., adsorption isotherms, surface heterogeneity, saturation capacities, and
      equilibrium constants) chromatographic methods. The confrontation of these two
      approaches confirmed the impossibility of a sound physical interpretation of the
      conventional Van't Hoff plot. The classical linear chromatography theory assumes
      that retention is determined by the equilibrium thermodynamics of analytes
      between a homogeneous stationary phase and a homogeneous mobile phase (although
      there may be two or several types of interactions). From values of the
      experimental retention factors in a temperature interval and estimates of the
      activity coefficients at infinite dilution in the same temperature interval
      provided by the UNIFAC group contribution method, evidence is provided that such
      a retention model cannot hold. The classical Van't Hoff plot appears meaningless
      and its linear behavior a mere accident. Results from nonlinear chromatography
      confirm these conclusions and provide explanations. The retention factors seem to
      fulfill the Van't Hoff equation, not the Henry constants corresponding to the
      different types of adsorption sites. The saturation capacities and the adsorption
      energies are clearly temperature dependent. The temperature dependence of these
      characteristics of the different assorption sites are different in aqueous
      methanol and acetonitrile solutions.

PMID- 16808478
TI  - Fabrication of conductive membrane in a polymeric electric field gradient
      focusing microdevice.
AB  - A novel approach to integrating a buffer ion-permeable membrane in a
      poly(glycidyl methacrylate-co-methyl methacrylate) micro electric field gradient
      focusing (muEFGF) device is described. A weir structure on which the membrane was
      positioned was fabricated between the separation channel and field gradient
      generating channel. Before formation of the membrane, the surface of the
      polymeric microdevice was treated for covalent bonding of the membrane. Following
      surface modification, a prepolymer solution containing poly(ethylene glycol)
      acrylate/methacrylate and Tris-HCl buffer was loaded into the microdevice. Low
      pressure nitrogen gas was then purged through the separation and field gradient
      generating channels to remove the prepolymer solution from these channels.
      Residual prepolymer solution was retained on the weir structure due to surface
      tension. Finally, the premembrane was cured in place on the weir using UV
      radiation. Using a muEFGF device, green fluorescent protein (GFP) was
      concentrated 4000-fold. Separation of GFP and R-phycoerythrin, and selective
      elution of GFP from a protein mixture containing GFP, FITC-labeled casein, and
      FITC-labeled hemoglobin were also demonstrated. It was found that the membrane
      conductivity and presence of carboxylic acid impurities in the membrane strongly
      affected the behavior of the muEFGF device.

PMID- 16808479
TI  - GC/multiple collector-ICPMS method for chlorine stable isotope analysis of
      chlorinated aliphatic hydrocarbons.
AB  - Stable isotopic characterization of chlorine in chlorinated aliphatic pollution
      is potentially very valuable for risk assessment and monitoring remediation or
      natural attenuation. The approach has been underused because of the complexity of
      analysis and the time it takes. We have developed a new method that eliminates
      sample preparation. Gas chromatography produces individually eluted sample peaks
      for analysis. The He carrier gas is mixed with Ar and introduced directly into
      the torch of a multicollector ICPMS. The MC-ICPMS is run at a high mass
      resolution of >/=10 000 to eliminate interference of mass 37 ArH with Cl. The
      standardization approach is similar to that for continuous flow stable isotope
      analysis in which sample and reference materials are measured successively. We
      have measured PCE relative to a laboratory TCE standard mixed with the sample.
      Solvent samples of 200 nmol to 1.3 micromol (24-165 microg of Cl) were measured.
      The PCE gave the same value relative to the TCE as measured by the conventional
      method with a precision of 0.12 per thousand (2x standard error) but poorer
      precision for the smaller samples.

PMID- 16808480
TI  - Specific affinity extraction method for small molecule-binding proteins.
AB  - Validation of the targets of candidate drugs is critical for rapid and efficient
      drug discovery and development and for understanding the pharmacological action
      and potential toxicities of the prospective therapeutic agent. Due to the
      nonspecific binding of abundant proteins to small molecule-immobilized gels, it
      is difficult to identify the protein targets of small molecules from crude
      biological samples by affinity extraction. To address this problem, we have
      developed an affinity gel for the specific extraction of small molecule-binding
      proteins. We immobilized small molecules on the agarose gel through a disulfide
      linker that is cleavable by mild reduction. This system has allowed specific and
      noncovalent complex formation between the small molecule and the target protein,
      keeping the effect of the nonspecific abundant proteins adsorbed on both the
      linker and gel surface to minimum. By preparing this affinity matrix with
      deoxycholate as a model small molecule, we captured two independent deoxycholate
      binding proteins of different affinities from mouse ascites, anti-deoxycholate
      antibody, and serum albumin. As other proteins were not captured, this affinity
      extraction method should contribute significantly to the accurate and rapid drug
      discovery and development.

PMID- 16808481
TI  - Ozone monitoring based on a biosensor concept utilizing a reagentless alcohol
      oxidase electrode.
AB  - An electrochemical method based on the concept of a biosensor for the monitoring
      of ozone is described for first time. The proposed method includes two parts: a
      selective sorbent for ozone, that is, eugenol, and a formaldehyde amperometric
      biosensor mounted into a flow-through cell. Ozone adds rapidly to the double bond
      of the allyl group of eugenol, which has been immobilized onto a hydrophobic C-18
      reactor and the so produced formaldehyde is collected into the working buffer
      solution (sampler) and pumped to the detector. A multimembrane assembly
      consisting of an alcohol oxidase-modified nylon membrane sandwiched between an
      outer polycarbonate and an inner cellulose acetate membrane was fitted onto a Pt
      electrode and the enzymatically produced H2O2 was monitored at +0.65 V (vs
      Ag/AgCl/KCl 3 M). Under optimum conditions, a linear calibration curve over the
      concentration range 3-200 microg x mL(-1) ozone was constructed. The detection
      limit (S/N = 3) was calculated at 1.1 microg x mL(-1) ozone. The proposed method
      is interference-free from other gases such as O2, Ar, N2, N2O, NOCl, SO2, NH3,
      and CO2, which were tested at concentrations >200-fold higher than that of 100
      microg x mL(-1) ozone used for comparison. Besides selectivity, the method is
      easy to perform and reproducible; its applicability in synthetic gaseous samples
      is also demonstrated.

PMID- 16808482
TI  - Investigation of sodium sulfate phase transitions in a porous material using
      humidity- and temperature-controlled X-ray diffraction.
AB  - Crystals growing in confined spaces can generate stress and are a major cause of
      damage in porous materials. To investigate such deleterious processes,
      appropriate in situ techniques are required. This paper describes the use of X
      ray diffractometry under controlled conditions of temperature and relative
      humidity (RH-XRD) for the direct observation of phase transition reactions in a
      porous substrate. An improved environmental chamber without temperature gradients
      is presented and applied to the investigation of phase transformations in the
      system Na2SO4 + H2O. This salt is generally considered as particularly damaging
      and frequently used in accelerated weathering tests. It is demonstrated that RH
      XRD can be successfully applied for the direct observation of several relevant
      phase transitions in glass frits used as porous substrates. The conversion of
      Na2SO4(III) to Na2SO4(V) and the hydration of Na2SO4(V) both proceed fairly
      rapidly as true solid-state reactions without deliquescence of the educt phases.
      In contrast, crystallization from solution is kinetically hindered as there is a
      strong tendency of aqueous Na2SO4 to form supersaturated solutions also in narrow
      pores. The important implications of this behavior of the salt are also briefly
      discussed in the paper.

PMID- 16808483
TI  - Upconversion fluorescence resonance energy transfer in a homogeneous immunoassay
      for estradiol.
AB  - We recently described a novel homogeneous assay principle based on upconversion
      fluorescence resonance energy transfer (UC-FRET), where an upconverting phosphor
      (UCP) is utilized as a donor. The UC-FRET has now been applied to a competitive
      homogeneous immunoassay for 17beta-estradiol (E2) in serum, using a small
      molecular dye as an acceptor. The assay was constructed by employing an UCP
      coated with an E2-specific recombinant antibody Fab fragment as a donor and an E2
      conjugated small-molecular dye, Oyster-556, as an acceptor. Standard curves for
      the assay were produced both in buffer and in male serum. Sensitized acceptor
      emission was measured at 600 nm under continuous laser diode excitation at 980
      nm. In buffer, the IC50 value of the assay was 1 nM and in serum 3 nM. The lower
      limits of detection (mean of zero calibrators, 3 SD) were 0.4 and 0.9 nM,
      respectively. The measurable concentration range extended up to 3 nM in buffer
      and 9 nM in serum. Equilibrium in the assay was reached in 30 min. The novel
      principle of UC-FRET has unique advantages compared to present homogeneous
      luminescence-based methods and can enable an attractive assay system platform for
      clinical diagnostics and for high-throughput screening approaches.

PMID- 16808484
TI  - Screening of nerve agent degradation products by MALDI-TOFMS.
AB  - A novel method for the rapid screening of degradation products derived from nerve
      agents by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry is described. Five standard products were selected as model
      compounds, including isopropyl methylphosphonic acid (IMPA), pinacolyl
      methylphosphonic acid (PMPA), ethyl methylphosphonic acid (EMPA), isobutyl
      methylphosphonic acid (i-BuMPA), and cyclohexyl methylphosphonic acid (CHMPA),
      which are degradation products of Sarin (GB), Soman (GD), VX, Russian VX (RVX),
      and GF, respectively. For comparison, CHCA (alpha-cyano-4-hydroxycinnamic acid)
      and DCCA (7-(diethylamino)coumarin-3-carboxylic acid) were used as the MALDI
      matrix when the third harmonic generation (355 nm) of a Nd:YAG laser and a
      hydrogen Raman laser (multifrequency laser) were used, respectively. The method
      permitted the five nerve agent degradation products to be screened rapidly and
      successfully, suggesting that it has the potential for use as a routine
      monitoring tool.

PMID- 16808485
TI  - Enhancement of amino acid detection and quantification by electrospray ionization
      mass spectrometry.
AB  - A new strategy for amino acid analysis is reported involving derivatization with
      an N-hydroxysuccinimide ester of N-alkylnicotinic acid (Cn-NA-NHS) followed by
      reversed-phase chromatography and electrospray ionization mass spectrometry (RPC
      MS). Detection sensitivity increased as the N-alkyl chain length of the nicotinic
      acid derivatizing agent was increased from 1 to 4. N-Acylation of amino acids
      with the Cn-NA-NHS reagents in water produced a stable product in roughly 1 min
      using a 4-fold molar excess of derivatizing agent in 0.1 M sodium borate buffer
      at pH values ranging from 8.5 to 10. Some O-acylation of tyrosine was also
      observed, but the product hydrolyzed within a few minutes at pH 10. The cystine
      product also degraded slowly over the course of a few days from reduction of the
      disulfide bond to form cysteine. The retention time of Cn-NA derivatized amino
      acids was lengthened in reversed-phase chromatography to the extent that polar
      amino acids were retained beyond the solvent peak, particularly in the cases of
      the C3-NA and C4-NA derivatives. Complete resolution of 18 amino acids was
      achieved in 28 min using the C4-NA-NHS reagent. Compared to N-acylation with
      benzoic acid, derivatization with C4-NA-NHS increased MS detection sensitivity 6
      80-fold. This was attributed to the surfactant properties of the Cn-NA-NHS
      reagents. The quaternary amine increased the charge on amino acid conjugates
      while the presence of an adjacent alkyl chain further increased ionization
      efficiency by apparently enhancing amino acid migration to the surface of
      electrospray droplets. Further modification of the Cn-NA-NHS reagents with
      deuterium was used to prepare coded sets of derivatizing agents. These coding
      agents were used to differentially code samples and after mixing carry out
      comparative concentration measurements between samples using extracted ion
      chromatograms to estimate relative peak areas of derivatized amino acids.

PMID- 16808486
TI  - Kinetic monitoring of electrophoretically induced solute reaction by axial
      absorption detection with liquid-core waveguide.
AB  - Teflon AF-2400 capillary has been used for capillary electrophoretic separation
      as well as for liquid-core waveguide for axial absorption detection. This
      separation/detection scheme has allowed continuous monitoring of
      electrophoretically induced reactions. In this paper, the decomposition of Cd2+
      complex with 4-(2-pyridylazo)resorcinol has been tested, and its decomposition
      kinetics has been studied. A simple modeling has predicted the single-exponential
      decay of the absorbance detected by the present axial absorption detector and has
      allowed the estimation of the decomposition rate constant for this reaction.

PMID- 16808487
TI  - Apparatus for pressurized planar electrochromatography in a completely closed
      system.
AB  - Pressurized planar electrochromatography (PPEC) is the mode which offers much
      higher separation efficiency in comparison to conventional planar chromatography,
      including both higher performance and much higher speed of separation. In this
      paper, we present a new device for performing PPEC in which the whole area of the
      chromatographic plate is pressurized. Both electrodes (anode and cathode) are
      washed with the mobile phase during the experiment, which prevents gas bubbles
      from collection in the region of the electrodes. This device enables directly
      controlling the flow rate of the mobile phase during the electrochromatography
      process. Mobile phase control offers the possibility of researching the influence
      of various properties of the PPEC system on separation efficiency. One important
      relationship to investigate is plate height vs mobile phase flow rate. This
      relationship helps to choose the optimal value of the mobile phase flow rate
      during the separation process. Considerable difference in shape of this
      relationship is demonstrated for conventional planar chromatography plates and
      high performance planar chromatography plates. Examples of the influence of some
      properties of the separating system on flow rate of the mobile phase are
      demonstrated, such as the buffer concentration in the mobile phase, the pH value
      of the buffer solution of the mobile phase, the type of chromatographic plate,
      and the voltage applied to the electrodes.

PMID- 16808488
TI  - Selective photoelectrochemical detection of DNA with high-affinity
      metallointercalator and tin oxide nanoparticle electrode.
AB  - Selective detection of double-stranded DNA (ds-DNA) in solution was achieved by
      photoelectrochemistry using a high-affinity DNA intercalator, Ru(bpy)2dppz (bpy =
      2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine) as the signal indicator
      and tin oxide nanoparticle as electrode material. When Ru(bpy)2dppz alone was
      irradiated with 470-nm light, anodic photocurrent was detected on the
      semiconductor electrode due to electron injection from its excited state into the
      conduction band of the electrode. The current was sustained in the presence of
      oxalate in solution, which acted as a sacrificial electron donor to regenerate
      the ground-state metal complex. After addition of double-stranded calf thymus DNA
      into the solution, photocurrent dropped substantially. The drop was attributed to
      the intercalation of Ru(bpy)2dppz into DNA and, consequently, the reduced mass
      diffusion of the indicator to the electrode, as well as electrostatic repulsion
      between oxalate anion and negative charges on DNA. The degree of signal reduction
      was a function of the DNA concentration, thus forming the basis for real-time DNA
      detection. The signal reduction was selective for ds-DNA, as no such effect was
      observed for single-stranded polynucleotides such as poly-G, poly-C, poly-A, and
      poly-U. The detection limit of calf thymus ds-DNA reached 1.8 x 10(-10) M in
      solution.

PMID- 16808489
TI  - Label-free electrochemical detection of protein based on a ferrocene-bearing
      cationic polythiophene and aptamer.
AB  - Two label-free electrochemical methods for the detection of human alpha-thrombin
      using a water-soluble, ferrocene-functionalized polythiophene transducer and a
      single-stranded oligonucleotide aptamer probe are described. The first approach
      is a direct method in which the recorded current decreases upon addition of the
      targeted protein. The second one requires more steps and the additional
      utilization of PNA probes and nuclease enzyme. This indirect method leads to an
      increase of the electrical signal as a function of the concentration of human
      alpha-thrombin with a detection limit of 75 fmol.

PMID- 16808490
TI  - Improving nanoprobes using surface-enhanced Raman scattering from 30-nm hollow
      gold particles.
AB  - We report the development of nanoprobes that exploit the surface-enhanced Raman
      scattering (SERS) from nonaggregated, hollow, gold nanospheres (HGNSs). The
      homogeneity of the HGNSs leads to a nearly 10-fold improvement in signal
      consistency over standard silver SERS substrates, which translates into a
      significant increase in sensitivity and dynamic range for the model application
      of pH sensing. Moreover, the small size (30-nm diameter) of these SERS-active
      nanoparticles represents a major step in advancing sensing technology based on
      SERS, making this technology more amenable to intracellular sensing.

PMID- 16808491
TI  - Direct on-line method to monitor the dynamic structure of noncovalent titanium
      complexes in solution by using cold-spray ionization time-of-flight mass
      spectrometry.
AB  - In this paper, we report the feasibility of using the on-line cold-spray
      ionization time-of-flight mass spectrometry (CSI-TOFMS) method to monitor
      directly the labile noncovalent organometallic complexes formed in the
      substitution reaction between a chiral titanium asymmetric catalyst and organic
      acid in the toluene solvent. The comparison between the conventional ESI and CSI
      TOFMS spectra of [(S)1]2Ti2[(S)2]2 in THF indicated that the CSI-TOFMS is an
      effective method to characterize the structures of labile organometallic
      complexes in solution. A new strategy was designed so that [(S)1]2Ti2[(S)2]2 and
      organic acid solution were delivered independently to the CSI ion source by two
      infusion syringe pumps, and they mixed at a triple valve, and then the
      substitution reaction occurred in the sprayer. The mix and reaction time was
      approximately 5 s and can be adjusted by the length of the PEEK tube and the flow
      rate. The reaction products were ionized and detected directly by the CSI-TOFMS.
      Organic acids, such as formic, acetic, phenylpropionic, anisic, and para
      methoxylphenylactic acids, were investigated. From the on line CSI-TOFMS spectra,
      it is observed clearly that one or two (S)2 group(s) can be substituted by the
      added acid to form new species. The results obtained here demonstrated that the
      designed strategy with on line CSI-TOFMS is effective and reliable to elucidate
      the dynamic structure of noncovalent titanium complexes in reaction solution.

PMID- 16808492
TI  - Energy, charge, and spin transport in molecules and self-assembled nanostructures
      inspired by photosynthesis.
AB  - Electron transfer in biological molecules provides both insight and inspiration
      for developing chemical systems having similar functionality. Photosynthesis is
      an example of an integrated system in which light harvesting, photoinduced charge
      separation, and catalysis combine to carry out two thermodynamically demanding
      processes, the oxidation of water and the reduction of carbon dioxide. The
      development of artificial photosynthetic systems for solar energy conversion
      requires a fundamental understanding of electron-transfer reactions between
      organic molecules. Since these reactions most often involve single-electron
      transfers, the spin dynamics of photogenerated radical ion pairs provide
      important information on how the rates and efficiencies of these reactions depend
      on molecular structure. Given this knowledge, the design and synthesis of large
      integrated structures to carry out artificial photosynthesis is moving forward.
      An important approach to achieving this goal is the development of small,
      functional building blocks, having a minimum number of covalent bonds, which also
      have the appropriate molecular recognition sites to facilitate self-assembly into
      a complete, functional artificial photosynthetic system.

PMID- 16808493
TI  - Investigation of the mechanism of the intramolecular Scholl reaction of
      contiguous phenylbenzenes.
AB  - Two mechanisms of the Scholl reaction were investigated in the series 1, 2, ...,
      n-oligophenylbenzenes (n = 2, 3, 4, 6) at the B3LYP/6-31G(d) level of theory. A
      mechanism involving generation of a radical cation followed by C-C bond formation
      and dehydrogenation is unlikely on the basis of unfavorable energies of
      activation. A mechanism involving generation of an arenium cation followed by C-C
      bond formation and dehydrogenation is energetically feasible. An explanation for
      the facile polycondensation of hexaphenylbenzene to hexa-peri-hexabenzocoronene,
      where six new aryl-aryl bonds are formed, is provided. Kinetic simulations based
      on the calculated activation energies of the arenium cation mechanism predict
      that intermediates will not accumulate; this is supported by mass balance
      experiments. Reaction optimization studies suggest that PhI(O2CCF3)2/BF3.OEt2 or
      MoCl5 are superior to FeCl3 or AlCl3/CuCl2. This is a full account of our work
      reported partially as a communication previously (Rempala, P.; Kroulik, J.; King,
      B. T. J. Am. Chem. Soc. 2004, 126, 15002-15003).

PMID- 16808494
TI  - Shapes of antibody binding sites: qualitative and quantitative analyses based on
      a geomorphic classification scheme.
AB  - The topography of antibody binding sites has been classified into five types that
      evoke familiar geomorphic features of the Earth. The 229 antibody crystal
      structures from the Protein Data Bank were analyzed and classified into these
      classes. Relationships to previous topography classifications by Rees et al., who
      defined three classes, and Thornton et al., who defined four classes, are
      identified. An algorithm was developed to identify the antibody binding site
      class automatically based on the definition and the shape of the binding site. A
      three-dimensional convex hull was formed around the complementarity determining
      regions (CDRs) of the antibody. The convex hull was then "trimmed" to fit the
      binding site by using distance criteria and morphological techniques. Once the
      program identified the binding site shape, a statistical and distance based
      analysis was performed to classify automatically the antibody into one of the
      five geomorphic classes. The five antibody topography classes are as follows:
      cave (mostly hapten binders), crater (mostly protein and
      peptide/carbohydrate/nucleic acid binders), canyon, valley, and plain (mostly
      protein binders). Comparisons of the binding sites of empty and of complexed
      antibody binding sites gave an indication of how the shape of the binding site is
      influenced by binding of the antigen.

PMID- 16808495
TI  - Sequential O- and N-acylation protocol for high-yield preparation and
      modification of rotaxanes: synthesis, functionalization, structure, and
      intercomponent interaction of rotaxanes.
AB  - A pseudorotaxane consisting of a 24-membered crown ether and secondary ammonium
      salt with the hydroxy group at the terminus was quantitatively acylated by bulky
      acid anhydride in the presence of tributylphosphane as catalyst to afford the
      corresponding rotaxane in high yield. Large-scale synthesis without
      chromatographic separation was easily achieved. The ammonium group in the
      resulting rotaxane was quantitatively acylated with excess electrophile in the
      presence of excess trialkylamine. Various N-functionalized rotaxanes were
      prepared by this sequential double-acylation protocol. 1H NMR spectra and X-ray
      crystallographic analyses of the rotaxanes showed that the crown ether component
      was captured on the ammonium group in ammonium-type rotaxane by strong hydrogen
      bonding intercomponent interaction. The conformation around the ammonium group
      was fixed by the hydrogen-bonding interaction. Meanwhile, the conformation of the
      amide-type rotaxane was determined by the weak CH/pi interaction between the
      methylene group in crown ether and the benzene ring of the axle component. The N
      acylation of ammonium-type rotaxane is useful for the preparation of both
      functionalized rotaxanes and weak intercomponent interaction-based rotaxanes.

PMID- 16808496
TI  - Computational studies of ethynyl- and diethynyl-expanded tetrahedranes,
      prismanes, cubanes, and adamantanes.
AB  - B3LYP/6-31+G(d) and MP2/6-31+G(d) computations were performed on a series of
      ethynyl- and diethynyl-expanded tetrahedranes, prismanes, cubanes and
      adamantanes. Every ethynyl expansion reduces the ring strain energy of the cage.
      The deprotonation energies of the cage poly-ynes are exceptionally low; we
      estimate that the gas-phase deprotonation energy of the diethynyl-expanded cubane
      is about 309 kcal mol(-1). The ring and cage poly-ynes can serve as effective
      hosts of either lithium or sodium cation, where the best host maximizes the
      number of interactions of alkynyl groups with the cation at an ideal distance.
      Last, the vertical excitation energies of the poly-ynes and their conjugate bases
      suggest that the alkynyl groups are interacting through space. The poly-ynes
      express a broad range of absorption energies, indicating that these molecules are
      potential targets in expressly designed optical applications.

PMID- 16808497
TI  - Bulky alkylphosphines with neopentyl substituents as ligands in the amination of
      aryl bromides and chlorides.
AB  - Di(tert-butyl)neopentylphosphine (DTBNpP) in combination with palladium sources
      provided catalysts with comparable or better activity for the Hartwig-Buchwald
      amination of aryl bromides than tri(tert-butyl)phosphine (TTBP) under mild
      conditions. DTBNpP also provided effective catalysts for amination reactions of
      aryl chlorides at elevated temperatures. Further replacement of tert-butyl groups
      with neopentyl substituents resulted in less effective ligands for amination
      reactions. Computationally derived cone angles showed that replacement of a tert
      butyl group with a neopentyl group significantly increased the cone angle of the
      phosphine. The larger cone angle of DTBNpP than TTBP appears to correlate with
      the higher activity of catalysts derived from DTBNpP in the amination of aryl
      bromides. TTBP is a stronger electron donor than DTBNpP, which may explain the
      higher activity for TTBP-derived catalysts toward aryl chlorides.

PMID- 16808498
TI  - DFT calculations on the protonation of two 1,3-butadiyne units fixed in medium
      sized rings.
AB  - The N-bis-protonated forms of 1-azacyclotetradeca-3,5,10,12-tetrayne (19) and 1,8
      diazacyclotetradeca-3,5,10,12-tetrayne (20) were used as model systems to study
      the HCl addition to two 1,3-butadiyne units in close proximity using quantum
      chemical means. The model calculations were carried out mainly at the B3LYP/3-21G
      or 6-31G level. The basis set 6-311G was used for single-point calculations. The
      calculations reveal that 19 and 20 are preferably protonated at the C4 center
      accompanied by a transannular ring closure between C3 and C13 yielding the
      bicyclic systems 23 and 24, respectively. Further stabilization of these vinyl
      cations is achieved by a second transannular ring closure between C6 and C10
      leading to the 5-8-5 tricyclic systems 27 and 28, which are further stabilized by
      the addition of a chloride anion. The different regiochemistry experimentally
      observed for 13b and 16b was rationalized by calculating local softness
      parameters. The observed product selectivities for the formation of 14b and 15b
      were traced back to the relative stabilities of the primary protonation products
      23 and 24, respectively. Model calculations on 1-azacyclopentadeca-3,5,11,13
      tetrayne (65) and 1-azacyclohexa-deca-3,5,12,14-tetrayne (66) as examples for
      medium-sized rings with nonparallel 1,3-butadiyne units revealed a concerted
      process of protonation and C3-C15 (65) or C3-C16 (66) ring closure. The second
      step is the formation of an aromatic central ring as a result of a ring closure
      between C6-C13 and C6-C14, respectively.

PMID- 16808499
TI  - Urea-, thiourea-, and guanidine-linked glycooligomers as phosphate binders in
      water.
AB  - Beta-(1-->6)-linked pseudodi- and pseudotrisaccharides incorporating alternating
      pseudoamide-type (urea, thiourea, guanidine) intersaccharide bridges have been
      prepared and evaluated as phosphate binders in water. The monosaccharide subunits
      induce the Z,Z rotameric form at the pseudoamide segments, thus favoring their
      participation in bidentate hydrogen-bond interactions with oxoanions. Moreover,
      the conformational properties about the anomeric C-1-N bonds and the sugar C-5--C
      6 bonds privilege orientations that facilitate both the desolvation of the
      incoming anionic guest and the stabilization of the complex by cooperative
      interactions. Measurable association constants (K(as)) toward dimethyl and,
      especially, phenyl phosphate were obtained from NMR titration experiments for
      both series of glucooligomers, the binding affinity being strongly dependent on
      the nature of the pseudoamide functionality. Guanidinium derivatives, for which
      charge neutralization was expected to contribute to phosphate binding, were
      superior to the neutral thiourea and urea derivatives (K(as) = 48-60 M(-1) for
      1:1 complexes with phenyl phosphate dianion). Interestingly, the thiourea
      oligomers exhibited association constants of the same order of magnitude (K(as) =
      25-40 M(-1)), much higher than those observed for the urea analogues (K(as) = 2-3
      M(-1)), which is ascribed to a less efficient solvation of the thiocarbonyl
      derivatives.

PMID- 16808500
TI  - Study of aromatic nucleophilic substitution with amines on nitrothiophenes in
      room-temperature ionic liquids: are the different effects on the behavior of para
      like and ortho-like isomers on going from conventional solvents to room
      temperature ionic liquids related to solvation effects?
AB  - The kinetics of the nucleophilic aromatic substitution of some 2-L-5
      nitrothiophenes (para-like isomers) with three different amines (pyrrolidine,
      piperidine, and morpholine) were studied in three room-temperature ionic liquids
      ([bmim][BF4], [bmim][PF6], and [bm(2)im][BF4], where bmim = 1-butyl-3
      methylimidazolium and bm(2)im = 1-butyl-2,3-dimethylimidazolium). To calculate
      thermodynamic parameters, a useful instrument to gain information concerning
      reagent-solvent interactions, the reaction was carried out over the temperature
      range 293-313 K. The reaction occurs faster in ionic liquids than in conventional
      solvents (methanol, benzene), a dependence of rate constants on amine
      concentration similar to that observed in methanol, suggesting a parallel
      behavior. The above reaction also was studied with 2-bromo-3-nitrothiophene, an
      ortho-like derivative able to give peculiar intramolecular interactions in the
      transition state, which are strongly affected by the reaction medium.

PMID- 16808501
TI  - Synthesis of a library of xylogluco-oligosaccharides for active-site mapping of
      xyloglucan endo-transglycosylase.
AB  - Complex oligosaccharides containing alpha-D-xylosyl-(1-->6)-beta-D-glucosyl
      residues and unsubstituted beta-(1-->4)-linked D-glucosyl units were readily
      synthesized using enzymatic coupling catalyzed by the Cel7B E197A glycosynthase
      from Humicola insolens. Constituting this library required four key steps: (1)
      preparing unprotected building blocks by chemical synthesis or enzymatic
      degradation of xyloglucan polymers; (2) generating the donor synthon in the
      enzymatic coupling by temporarily introducing a lactosyl motif on the 4-OH of the
      terminal glucosyl units of the xylogluco-oligosaccharides; (3) synthesizing the
      corresponding alpha-fluorides, followed by their de-O-acetylation and the
      glycosynthase-catalyzed condensation of these donors onto various acceptors; and
      (4) enzymatically releasing lactose or galactose from the reaction product,
      affording the target molecules in good overall yields. These complex
      oligosaccharides proved useful for mapping the active site of a key enzyme in
      plant cell wall biosynthesis and modification: the xyloglucan endo
      transglycosylase (XET). We also report some preliminary enzymatic results
      regarding the efficiency of these compounds.

PMID- 16808502
TI  - Generation of acyloxyketenes from unstable mesoionic 1,3-dioxolium-4-olates and
      their reaction with ketenophiles to give [2 + 2] cycloadducts.
AB  - Fast ring opening of mesoionic 1,3-dioxolium-4-olates, generated by Rh(2)(OAc)(4)
      catalyzed decomposition of phenyldiazoacetic anhydride derivatives, to
      acyloxyphenylketenes was demonstrated by trapping the ketenes with several
      ketenophiles. Reactions of phenyldiazoacetic anhydride derivatives with several
      ketenophiles such as dihydrofuran, carbodiimides, and imines were carried out. No
      1,3-dipolar cycloadducts of the latter with 1,3-dioxolium-4-olates were observed.
      Instead, only their [2 + 2]-cycloadducts with the acyloxyketenes generated by
      ring-opening of the initially formed 1,3-dioxolium-4-olates were isolated. In the
      reaction with cyclopentadiene, 1,3-dipolar cycloadducts with 1,3-dioxolium-4
      olates were formed as main products along with the [2 + 2]-ketene adduct. PM3
      calculation of heats of formation of 2,5-diphenyl-1,3-dioxolium-4-olate and the
      corresponding benzoyloxyphenylketene indicates that the ring-opened
      acyloxyketenes are ca. 9 kcal/mol more stable than the corresponding 1,3
      dioxolium-4-olates.

PMID- 16808503
TI  - Nucleophilic substitution reactions of sulfur-substituted cyclohexanone acetals:
      an analysis of the factors controlling stereoselectivity.
AB  - The reactions of cyclohexanone acetals substituted with thiophenyl groups (and
      other heteroatoms) at C-2 demonstrate the powerful influence that these
      substituents have on the stereoselectivity of nucleophilic substitution
      reactions. The trans selectivities of these reactions correlate with the behavior
      of the corresponding ketones. These experiments lend support to the possibility
      that the reactions of the acetals, which proceed via oxocarbenium ions, are
      operating under Felkin-Anh control.

PMID- 16808504
TI  - Sonochemistry: a powerful way of enhancing the efficiency of carbohydrate
      synthesis.
AB  - Using sonication as a means of facilitating organic reactions in carbohydrate
      chemistry was explored under the conditions used for traditional organic
      synthesis. An array of representative reactions, including hydroxy group
      manipulation (acylation, protection/deprotection, acyl group migration),
      thioglycoside synthesis, azidoglycoside synthesis, 1,3-dipolar cycloaddition and
      reductive cleavage of benzylidene, commonly used in the synthesis of carbohydrate
      derivatives was examined. A series of glycosylation reactions that employ
      thioglycosides, glycosyl trichloroacetimidate, glycosyl bromide and glycosyl
      acetate as the glycosyl donors was also examined. Our results demonstrate that
      sonication can significantly shorten the reaction time, enhance the reactivity of
      reactant and lead to superior yield and excellent stereoselectivity. More
      importantly, a general protocol of glycosylation may finally be developed.
      Sonication is compatible to the conditions used for traditional organic
      synthesis. We believe that sonication can also be applied to other areas of
      synthetic processes.

PMID- 16808505
TI  - Synthesis and characterization of oligoproline-based molecular assemblies for
      light harvesting.
AB  - Helical oligoproline arrays provide a structurally well-defined environment for
      building photochemical energy conversion assemblies. The use of solid-phase
      peptide synthesis (SPPS) to prepare four such arrays, consisting of 16, 17, 18,
      and 19 amino acid residues, is described here. Each array contains the
      chromophore [Rub'(2)m](PF(6))(2) (b' = 4,4'-diethylamidocarbonyl-2,2'-bipyridine;
      m = 4-methyl-2,2'-dipyridine-4'-carboxylic acid) and the electron transfer donor
      PTZ (phenothiazine). The arrays differ systematically in the distance between the
      redox-active metal complex and PTZ sites. They have been used in photophysical
      studies to provide insight into the distance dependence of electron transfer. (J.
      Am. Chem. Soc. 2004, 126, 14506-14514). This work describes the synthesis,
      purification, and characterization of the oligoproline arrays, including a
      general procedure for the synthesis of related arrays.

PMID- 16808506
TI  - Lewis acid-promoted rearrangement of 2,3-epoxy alcohol derivatives:
      stereochemical control and selective formation of two types of chiral quaternary
      carbon centers from the single carbon skeleton.
AB  - The Lewis acid-promoted rearrangement of 2,2,3,3-tetrasubstituted 2,3-epoxy
      alcohols with several kinds of protecting groups was investigated. When SnCl4 is
      used as a Lewis acid, the reaction proceeds in a regio- and stereo-controlled
      manner to afford two types of carbonyl compounds selectively from a single 2,3
      epoxy alcohol only by changing the protecting group of the alcohol. The method
      was then applied to the formation of two types of acyclic and cyclic quaternary
      carbon centers from the single compound in optically active forms.

PMID- 16808507
TI  - Synthesis of 2,4-disubstituted piperidines via radical cyclization: unexpected
      enhancement in diastereoselectivity with tris(trimethylsilyl)silane.
AB  - A novel approach to 2,4-disubstituted piperidines is reported, involving the
      radical cyclization of 7-substituted-6-aza-8-bromooct-2-enoates. Cyclization with
      tributyltin hydride affords the trans piperidines with trans/cis diastereomeric
      ratios ranging typically from 3:1 to 6:1. Cyclization with
      tris(trimethylsilyl)silane affords the same products with diastereomeric ratios
      of up to 99:1 in certain cases. The enhancement in diastereoselectivity results
      from the selective rearrangement of the minor stereoisomer through a cascade
      process involving radical cyclization to the piperidine radical, 1,5-radical
      translocation, and attack of the translocated radical onto the sulfonamide with
      extrusion of SO2 in a Smiles-type rearrangement. Slower trapping of the
      piperidine radical by tris(trimethylsilyl)silane compared to tributyltin hydride
      accounts for the occurrence of the rearrangement cascade in the former case.

PMID- 16808508
TI  - Total synthesis and biological evaluation of neodysiherbaine A and analogues.
AB  - Dysiherbaine (1) and its congener neodysiherbaine A (2) are naturally occurring
      excitatory amino acids with selective and potent agonistic activity for
      ionotropic glutamate receptors. We describe herein the total synthesis of 2 and
      its structural analogues 3-8. Advanced key intermediate 16 was employed as a
      branching point to assemble a series of these analogues 3-8 with respect to the
      C8 and C9 functionalities, which would not have been accessible through
      manipulations of the natural product itself. The synthesis of key intermediate 16
      features (i) stereocontrolled C-glycosylation to set the C6 stereocenter, (ii)
      concise synthesis of the bicyclic ether skeleton through chemo- and
      stereoselective dihydroxylation of the exo-olefin and stereoselective epoxidation
      of the endo-olefin, followed by epoxide ring opening/5-exo ring closure, and
      (iii) catalytic asymmetric hydrogenation of enamide ester to construct the amino
      acid appendage. A preliminary biological evaluation of analogues for their in
      vivo toxicity against mice and binding affinity for glutamate receptors showed
      that both the type and stereochemistry of the C8 and C9 functional groups
      affected the subtype selectivity of dysiherbaine analogues for members of the
      kainic acid receptor family.

PMID- 16808509
TI  - Stereoselective total synthesis of (+)-streptazolin by using a temporary silicon
      tethered RCM strategy.
AB  - A stereoselective total synthesis of (+)-streptazolin 1 was accomplished starting
      from readily available aminocyclopentenol (-)-7. The synthetic sequence
      highlights an intramolecular aldol condensation strategy to construct the
      piperidine core and a silicon-tethered ring-closing metathesis strategy to
      install the Z exocyclic ethylidene side chain of streptazolin. Separate
      protodesilylation and Tamao oxidation of a common intermediate 32 afforded
      streptazolin and the precursor for 13-hydroxystreptazolin. The overall yield for
      (+)-streptazolin 1 from aminocyclopentenol (-)-7 was 4.8% for a total of 16
      steps.

PMID- 16808510
TI  - Enzymatic approach to enantiomerically pure 5-alken-2,4-diols and 4-hydroxy-5
      alken-2-ones: application to the synthesis of chiral synthons.
AB  - Enantiomerically pure 1,3-diols 1-3 were obtained by a chemoenzymatic approach
      (lipase PS from Burkholderia cepacia). These diols were converted into useful
      chiral synthons, which could be considered homologues of glyceraldehyde and
      glyceric acid acetonides. Applications of these synthons to the de novo synthesis
      of sugars and preparation of conagenin carboxylic moiety were shown. Hydroxy
      ketone 4 was chosen as a model system for another synthetic evolution: it was
      obtained in enantiomerically pure form by enzymatic resolution and converted into
      chiral tetrahydropyranes, such as the stereoisomers of the commercial fragrance
      Gyrane.

PMID- 16808511
TI  - Interplay between intramolecular resonance-assisted hydrogen bonding and
      aromaticity in o-hydroxyaryl aldehydes.
AB  - In this work, we analyze a series of o-hydroxyaryl aldehydes to discuss the
      interrelation between the resonance-assisted hydrogen bond (RAHB) formation and
      the aromaticity of the adjacent aromatic rings. As compared to the nonaromatic
      reference species (malonaldehyde), the studied compounds can be separated into
      two groups: first, the set of systems that have a stronger RAHB than that of the
      reference species, for which there is a Kekule structure with a localized double
      CC bond linking substituted carbon atoms; and second, the systems having a weaker
      RAHB than that of the reference species, for which only pi-electrons coming from
      a localized Clar pi-sextet can be involved in the RAHB. As to aromaticity, there
      is a clear reduction of aromaticity in the substituted ipso ring for the former
      group of systems due to the formation of the RAHB, while for the latter group of
      species only a slight change of local aromaticity is observed in the substituted
      ipso ring.

PMID- 16808512
TI  - Lewis acid-catalyzed [4 + 2] benzannulation between enynal units and enols or
      enol ethers: novel synthetic tools for polysubstituted aromatic compounds
      including indole and benzofuran derivatives.
AB  - The reaction of enynals 1, including o-(alkynyl)benzaldehydes, and carbonyl
      compounds 2, such as aldehydes and ketones, in the presence of a catalytic amount
      of AuBr3 in 1,4-dioxane at 100 degrees C gave the functionalized aromatic
      compounds 3 in high yields. Similarly, the AuBr3-catalyzed reactions of 1 with
      acetal compounds 5 afforded the corresponding aromatic compounds 3 in good
      yields. On the other hand, when the reaction was carried out in the presence of a
      catalytic amount of Cu(NTf2)2 and 1 equiv of H2O in (CH2Cl)2 at 100 degrees C,
      the decarbonylated naphthalene products 4 were obtained selectively over 3.
      Benzofused heteroaromatic compounds, such as indole derivatives 13 and benzofuran
      derivatives 15, were also synthesized by using the present benzannulation
      methodology.

PMID- 16808513
TI  - Rearrangements of the Diels-Alder cycloadducts obtained from acetylenic sulfones
      and 1,3-diphenylisobenzofuran.
AB  - 1,3-Diphenylisobenzofuran afforded Diels-Alder cycloadducts 4a,b with n-butyl-
      and phenyl-substituted acetylenic sulfones 3a,b, respectively. The products
      underwent various types of rearrangements under pyrolytic, acid-catalyzed, and
      photochemical conditions. In the presence of acid, or upon heating in xylenes,
      they afforded the ketones 5a,b. In addition, the dehydration product 7a was
      produced from the pyrolysis of 4a, and the unexpected transposed ketone 6b was
      generated under acid-catalyzed or pyrolytic conditions from 4b via a postulated
      epoxide intermediate. The photolysis of 4a afforded ketone 5a as the sole
      isolated product, whereas 5b afforded oxepin 8b and indenyl phenyl ketone 9b. The
      formation of the latter two products can be rationalized by a series of
      pericyclic reactions. These include an intramolecular [2+2] cycloaddition,
      followed by a 1,3-dipolar cycloreversion, for the transformation of 4b to 8b and
      a series of electrocyclic and [1,3]sigmatropic reactions to convert 8b into 9b.

PMID- 16808514
TI  - Reactivity and acid-base behavior of ring-methoxylated arylalkanoic acid radical
      cations and radical zwitterions in aqueous solution. Influence of structural
      effects and pH on the benzylic C-H deprotonation pathway.
AB  - A product and time-resolved kinetic study of the one-electron oxidation of ring
      methoxylated phenylpropanoic and phenylbutanoic acids (Ar(CH2)nCO2H, n = 2, 3)
      has been carried out at different pH values. Oxidation leads to the formation of
      aromatic radical cations (Ar.+(CH2)nCO2H) or radical zwitterions (Ar.+(CH2)nCO2-)
      depending on pH, and pKa values for the corresponding acid-base equilibria have
      been measured. In the radical cation, the acidity of the carboxylic proton
      decreases by increasing the number of methoxy ring substituents and by increasing
      the distance between the carboxylic group and the aromatic ring. At pH 1.7 or
      6.7, the radical cations or radical zwitterions undergo benzylic C-H
      deprotonation as the exclusive side-chain fragmentation pathway, as clearly shown
      by product analysis results. At pH 1.7, the first-order deprotonation rate
      constants measured for the ring-methoxylated arylalkanoic acid radical cations
      are similar to those measured previously in acidic aqueous solution for the alpha
      C-H deprotonation of structurally related ring-methoxylated alkylaromatic radical
      cations. In basic solution, the second-order rate constants for reaction of the
      radical zwitterions with (-)OH (k-OH)) have been obtained. These values are
      similar to those obtained previously for the (-)OH-induced alpha-C-H
      deprotonation of structurally related ring-methoxylated alkylaromatic radical
      cations, indicating that under these conditions the radical zwitterions undergo
      benzylic C-H deprotonation. Very interestingly, with 3,4-dimethoxyphenylethanoic
      acid radical zwitterion, that was previously observed to undergo exclusive
      decarboxylation up to pH 10, competition between decarboxylation and benzylic C-H
      deprotonation is observed above pH 11.

PMID- 16808515
TI  - Mild and nonracemizing conditions for Ullmann-type diaryl ether formation between
      aryl iodides and tyrosine derivatives.
AB  - CuI/N,N-dimethylglycine-catalyzed coupling reaction of L-tyrosine derivatives and
      L-phenylalanine-derived iodides in the presence of Cs2CO3 works at 90 degrees C
      to provide the corresponding diaryl ether. Partial racemization occurs when N-Boc
      and N-Cbz-protected aromatic amino esters are used, while N-trityl- and N,N
      dibenzyl-protected aromatic amino esters give rise to coupling products without
      loss of optical purity. Little racemization is also observed in cases of N-Boc-
      and N-Cbz-protected aromatic amino acids as substrates. But their reaction yields
      are moderate. On the basis of these studies, shorter protocols for assembling
      (S,S)-isodityrosine and K-13 are developed.

PMID- 16808516
TI  - Pyridyl-supported pyrazolyl-N-heterocyclic carbene ligands and the catalytic
      activity of their palladium complexes in Suzuki-Miyaura reactions.
AB  - Palladium complexes of two new types of unsymmetrical pyridyl-supported pyrazolyl
      N-heterocyclic carbene ligands were synthesized and structurally characterized. A
      strategy to release the steric strain of the ligand was realized by the
      introduction of methylene linkers to the ligand molecule. All the palladium
      complexes exhibited good to excellent catalytic activity in Suzuki-Miyaura
      reactions of phenyl or p-tolylboronic acid with aryl halides including
      iodobenzene, aryl bromides, and activated aryl chlorides under mild conditions,
      revealing that the new ligands are promising for the construction of highly
      active transition-metal catalysts.

PMID- 16808517
TI  - Solid-phase synthesis of m-phenylene ethynylene heterosequence oligomers.
AB  - Both homo- and heterosequence m-phenylene ethynylene oligomers are synthesized
      using a conceptually simple iterative solid-phase strategy. Oligomers are
      attached to Merrifield's resin through a known triazene-type linkage. The
      phenylene ethynylene molecular backbone is constructed through a series of
      palladium-mediated cross-coupling reactions. The strategy employs two types of
      monomers that bear orthogonal reactivity, one being a monoprotected bisethynyl
      arene and the other being a 3-bromo-5-iodo arene. The catalyst conditions are
      tailored to the requirements of each monomer type. The monoprotected bisethynyl
      arene is coupled to the growing chain in 2 h at room temperature using a Pd(I)
      dimer precatalyst ((t)Bu3P(Pd(mu-Cl)(mu-2-methyl allyl)Pd)P(t)Bu3) in conjunction
      with ZnBr2 and diisopropylamine. In alternate steps, the resin is deprotected in
      situ with TBAF and coupled to the 3-bromo-5-iodo arene using the iodo selective
      Pd(tri-2-furylphosphine)4 catalyst in conjunction with CuI and piperidine; this
      reaction is also completed in 2 h at room temperature. These cross-coupling
      events are alternated until an oligomer of the desired length is achieved. The
      oligomer is then cleaved from the resin using CH(2)I(2)/I(2) at 110 degrees C and
      purified using preparatory GPC. Using this method, a series of homo- and
      heterosequence oligomers up to 12 units in length in excellent yield and purity
      were synthesized on the 100 mg scale. Longer oligomers were attempted; however,
      deletion sequences were found in oligomers longer than 12 units.

PMID- 16808518
TI  - Rhodium-catalyzed intermolecular chelation controlled alkene and alkyne
      hydroacylation: synthetic scope of beta-S-substituted aldehyde substrates.
AB  - The use of beta-S-substituted aldehydes in rhodium-catalyzed intermolecular
      hydroacylation reactions is reported. Aldehydes substituted with either sulfide
      or thioacetal groups undergo efficient hydroacylation with a variety of electron
      poor alkenes, such as enoates, in Stetter-like processes and with both electron
      poor and neutral alkynes. In general, the reactions with electron-poor alkenes
      demonstrate good selectivity for the linear regioisomer, and the reactions with
      alkynes provide enone products with excellent selectivity for the E-isomers. The
      scope of the process was shown to be broad, tolerating a variety of substitution
      patterns and functional groups on both reaction components. A novel CN-directing
      effect was shown to be responsible for reversing the regioselectivity in a number
      of alkyne hydroacylation reactions. Catalyst loadings as low as 0.1 mol % were
      achievable.

PMID- 16808519
TI  - Tautomeric and conformational properties of acetoacetamide: electron diffraction
      and quantum chemical study.
AB  - The tautomeric properties of acetoacetamide, CH3C(O)CH2C(O)NH2, have been
      investigated by gas electron diffraction (GED) and quantum chemical calculations
      (B3LYP and MP2 approximations with 6-31G(d,p) and 6-311++G(3df,pd) basis sets).
      GED results in a mixture of 63(7)% enol tautomer and 37(7)% diketo form at 74(5)
      degrees C. Only one enol form with the O-H bond adjacent to the methyl group
      (CH3C(OH)=CHC(O)NH2) and only one diketo conformer (with dihedral angles
      tau(O=C(CH3)-C-C) = 31.7(7.5) degrees and tau(O=C(NH2)-C(H2)-C(O)) = 130.9(4.5)
      degrees ) are present. The calculated tautomeric composition varies in a wide
      range depending on the quantum chemical method and basis set. Only the B3LYP
      method with small basis sets reproduces the experimental composition correctly.

PMID- 16808520
TI  - General and versatile entry to 4,5-fused polycyclic imidazolones systems. Use of
      the tandem transposition/pi-cyclization of N-acyliminium species.
AB  - A simple and efficient methodology for the synthesis of 4,5-fused imidazolidin-2
      ones from bicyclic and tricyclic ketones in a four-step sequence was described,
      by successive spirohydantoin Bucherer-Berg formation, mono- and dialkylation of
      the nitrogen atom of the hydantoin ring, regioselective reduction of one carbonyl
      function, and cationic cyclization associated with ring expansion. The key step
      of this sequential reaction was based on a tandem transposition/intramolecular
      amidoalkylation of cyclic spiro-N-acyliminium species. The process seems to be
      easy, general, regiospecific, resulted in the formation of polyheterocyclic
      systems containing an imidazolidin-2-one nucleus in good to excellent yields (67
      99%), and is compatible with a large-scale production (up to 3 g of product 14,
      for example). Also, this method allows the preparation of the novel heterocycles
      14 and 15 that have pharmaceutically interesting profiles, which are not
      accessible through short current synthetic methods. Finally, products 15 bear a
      secondary amide function crucial for further transformations, including the
      introduction of various pharmacophore groups either at the C or the N atoms of
      the imidazole ring.

PMID- 16808521
TI  - Anthralin: primary products of its redox reactions.
AB  - One-electron reduction significantly enhances the ability of anthralin, 1, to act
      as a hydrogen atom donor. On annealing of an MTHF glass in which the radical
      anion of anthralin, 1*-, is generated radiolytically, this species decays mainly
      by loss of H* to give the anthralyl anion, 2- . On the other hand, radicals
      formed on radiolysis of matrices that are suitable for the generation of radical
      anions or cations are capable to abstract H* from anthralin to give the anthralyl
      radical, 2* . Both 2- and 2* are obtained simultaneously by mesolytic cleavage of
      the radical anion of the anthralin dimer. Contrary to general assumptions, the
      anthralyl radical is found to be much more reactive toward oxygen than the anion.
      All intermediates are characterized spectroscopically and by reference to quantum
      chemical calculations. Attempts to generate the radical cation of anthralin by X
      irradiation of an Ar matrix containing anthralin led also to significant
      formation of its radical anion, i.e., anthralin acts apparently as an efficient
      electron trap in such experiments.

PMID- 16808522
TI  - Reaction of C-silylated alpha-diazophosphines as nucleophiles toward carbonyl
      compounds: a mechanistic study and application to the synthesis of alkynes and
      alpha-hydroxyphosphonamides.
AB  - Diversely substituted alpha-hydroxyphosphonamides and alkynes have been
      efficiently synthesized through the reaction of C-silylated alpha-diazophosphines
      with different types of aldehydes (2 equiv) in a neutral medium under very mild
      conditions. The reaction with some chiral aldehydes is highly diastereoselective
      leading to phosphonamides as single diastereomers. The novel reaction is
      influenced by electronic and steric effects being precluded for aromatic
      aldehydes containing electron-releasing substituents on the phenyl ring and for
      bulky aliphatic aldehydes. The mechanistic studies of these processes, which are
      highly exothermic, provide evidence for a nucleophilic attack of the
      diazophosphine to the aldehyde leading to a betaine that rapidly rearranges to a
      diazomethylenephosphorane, which has been detected or captured in some instances.
      The diazomethylenephosphorane reacts with a second molecule of aldehyde according
      to a Wittig-type condensation, and the rate-determining step of the whole process
      is believed to be the decomposition of the resultant oxaphosphetane to afford the
      hydroxyphosphonamide and a diazocumulene. Finally, this intermediate loses
      molecular nitrogen giving a transient carbene that rapidly evolves toward the
      alkyne.

PMID- 16808523
TI  - On the [2+2] cycloaddition of 2-aminothiazoles and dimethyl
      acetylenedicarboxylate. Experimental and computational evidence of a thermal
      disrotatory ring opening of fused cyclobutenes.
AB  - The reaction of 2-(phenylamino)- and 2-(dimethylamino)thiazoles with dimethyl
      acetylenedicarboxylate led unexpectedly to dimethyl 6-(phenylamino)- and 6
      (dimethylamino)-3,4-pyridinedicarboxylates. Those compounds reasonably result
      from a sequence of reactions initiated by a [2 + 2] cycloaddition of the alkyne
      to the formal C=C of the thiazole ring. These pyridines were obtained in nearly
      all the cases assayed as the exclusive reaction products under rather mild
      conditions and in fair to good yields. In contrast, the regioisomeric 2-amino-3,4
      pyridinedicarboxylates, which would result from a [4 + 2] cycloaddition followed
      by sulfur extrusion, were only obtained in one particular case. The two reaction
      paths leading alternatively to both regioisomers were investigated
      computationally. The respective [2 + 2] and [4 + 2] cycloadducts were found to be
      formed stepwise from a common dipolar intermediate. Notably, the step following
      the [2 + 2] cycloaddition (i.e., the ring opening of the fused cyclobutene
      intermediate to give an all-cis 1,3-thiazepine) was found to take place in a
      disrotatory mode. Although geometric constraints and electronic factors may
      reduce the energy for the disrotation, the implication of the fused five-membered
      ring in the electronic reorganization leading to the 1,3-thiazepine is
      determinant. In this sense, this step could be regarded also as a thermally
      allowed six-electron five-center disrotatory electrocyclic ring opening. The
      proposed mechanism was experimentally supported by the isolation of several
      intermediates and other experimental facts.

PMID- 16808524
TI  - Synthesis of substituted carbazoles, indoles, and dibenzofurans by vinylic to
      aryl palladium migration.
AB  - Substituted carbazoles, indoles, and dibenzofurans are readily prepared in
      moderate to excellent yields by the palladium-catalyzed cross-coupling of alkynes
      and appropriately substituted aryl iodides. This process proceeds by
      carbopalladation of the alkyne, heteroatom-directed vinylic to aryl palladium
      migration, and ring closure via intramolecular arylation or a Mizoroki-Heck
      reaction. Results from the deuterium labeling experiments are consistent with the
      proposed mechanism.

PMID- 16808525
TI  - Investigation into factors influencing stereoselectivity in the reactions of
      heterocycles with donor-acceptor-substituted rhodium carbenoids.
AB  - Rhodium-catalyzed decomposition of aryldiazoacetates in the presence of pyrroles
      or furans results in mono- or biscyclopropanation of the heterocycle, but with
      opposite enantioinduction. In the absence of sterically encumbering groups, the
      cyclopropanation of furan occurs with initial bond formation at the 2-position.
      If this pathway is sterically blocked, cyclopropanation can occur with initial
      bond formation at the 3-position of the furan ring; in this case, the
      cyclopropanation reaction takes place on the opposite face of the heterocycle,
      and the opposite enantioinduction is observed. Upon extension of this methodology
      to benzofurans, a highly enantioselective monocyclopropanation reaction occurs to
      furnish a product derived from initial bond formation at the 2-position of the
      benzofuran. When this reaction pathway is inhibited by sterically encumbering
      substituents on the benzofuran, no cyclopropanation of the furan ring is
      observed, and instead, double cyclopropanation of the benzene ring occurs. Double
      cyclopropanation of the benzene ring was also observed in reactions with indoles.

PMID- 16808526
TI  - Berkelic acid, a novel spiroketal with selective anticancer activity from an acid
      mine waste fungal extremophile.
AB  - Berkeley Pit Lake is an abandoned open-pit copper mine filled with 30 billion
      gallons of acidic, metal-contaminated water. This harsh environment is proving to
      be a source of unusual microorganisms that produce novel bioactive metabolites.
      Bioassay-guided fractionation using signal transduction enzyme assays led to the
      isolation of the novel spiroketal, berkelic acid 1, and of the known gamma
      pyrone, spiciferone A 4. Berkelic acid has shown selective, nanomolar activity
      against OVCAR-3, an ovarian cancer cell line in the National Cancer Institute
      cell line screen. The isolation and characterization of these compounds are
      reported here.

PMID- 16808527
TI  - Enantioselective synthesis of a key "A-ring" intermediate for the preparation of
      1alpha-fluoro vitamin D3 analogues.
AB  - 1Alpha-fluoro A-ring dienol 2, a useful building block for the preparation of
      fluorinated vitamin D3 analogues, was synthesized in eight steps from 4-{[tert
      butyldimethylsilyl]oxy}cyclohexanone. The most distinctive synthetic development
      to emerge from this new synthesis is an unprecedented substrate-controlled
      diastereoselective fluorodesilylation of an advanced dienylsilane intermediate.
      This is the first enantioselective route to compound 2 relying on the use of an
      electrophilic fluorinating reagent.

PMID- 16808528
TI  - Ring-closing metathesis-based synthesis of (3R,4R,5S)-4-acetylamino-5-amino-3
      hydroxy- cyclohex-1-ene-carboxylic acid ethyl ester: a functionalized cycloalkene
      skeleton of GS4104.
AB  - (3R,4R,5S)-4-Acetylamino-5-amino-3-hydroxy-cyclohex-1-ene-carboxylic acid ethyl
      ester, a functionalized cyclohexene skeleton of GS4104, was diastereoselectively
      synthesized. A major advantage of this synthesis is the use of readily available
      L-serine to replace frequently used (-)-shikimic acid or (-)-quinic acid as the
      starting material. Ring-closing metathesis and diastereoselective Grignard
      reactions successfully served as the key steps. Absolute configurations of the
      key intermediates were confirmed by corresponding two-dimensional NMR studies.

PMID- 16808529
TI  - An efficient, stereoselective synthesis of the hydroxyethylene dipeptide isostere
      core for the HIV protease inhibitor A-792611.
AB  - A stereoselective synthesis of the hydroxyethylene dipeptide isostere 1 is
      described. The route employs a substrate-directed kinetic protonation of an
      alpha/gamma-substituted lactone to afford the desired stereochemistry. A method
      for converting the diastereomerically enriched intermediate lactone to the ring
      open form with retention of stereochemistry is demonstrated. A novel procedure
      for utilizing N,N-dibromo-5,5-dimethylhydantoin in Hofmann rearrangements is
      disclosed. This route was used to prepare amino alcohol 1, the core portion of
      the HIV protease inhibitor A-792611, in 46% yield from phenylalanine-derived
      epoxide 2.

PMID- 16808530
TI  - Generation of benzocyclobutadiene derivatives from zirconaindene derivatives.
AB  - Zirconaindene derivatives produced benzocyclobutadiene derivatives in situ in the
      presence of CuCl and 1,4-naphthoquinone, which afforded their dimers, 6a,10b
      dihydrobenzo[a]biphenylenes and dibenzosemibullvalenes or
      dibenzo[a,e]cycloctenes.

PMID- 16808531
TI  - Practical synthesis of an L-fructose-derived ketone catalyst for asymmetric
      epoxidation of olefins.
AB  - An L-fructose-derived ketone catalyst for asymmetric epoxidation of trans- and
      trisubstituted olefins was efficiently prepared from L-sorbose in five steps.

PMID- 16808532
TI  - Efficient method for the deprotection of tert-butyldimethylsilyl ethers with
      TiCl4-Lewis base complexes: application to the synthesis of 1beta
      methylcarbapenems.
AB  - TiCl4-Lewis base (AcOEt, CH3NO2) complexes smoothly deprotected tert
      butyldimethylsilyl (TBDMS) ethers. The reaction velocity with these complexes,
      which seemed less reactive due to the influence of Lewis bases, was considerably
      greater than that with TiCl4 alone. Selective desilylations between aliphatic and
      aromatic TBDMS ethers (1 and 5), between 1 and benzyl, allyl, tosyl,
      methoxyphenyl, and chloroacetyl ethers (13, 14, 15, 16, and 17), and between
      TBDMS and TBDPS ethers (18 and 19) were successfully performed. Desilylation of
      TBDMS-aldol, acyloin, and beta-lactam analogues 9-12 proceeded smoothly due to
      anchimeric assistance by the neighboring carbonyl groups. The present method was
      successfully applied to the practical synthesis of 1beta-methylcarbapenems 20a'
      f'.

PMID- 16808533
TI  - A SeCSe-Pd(II) pincer complex as a highly efficient catalyst for allylation of
      aldehydes with allyltributyltin.
AB  - An air- and moisture-stable SeCSe-Pd(II) pincer complex was synthesized and found
      to catalyze the nucleophilic allylation of aldehydes with allyltributyltin. The
      allylation of a variety of aromatic and aliphatic aldehydes to give the
      corresponding homoallyl alcohols was performed at room temperature to 60 degrees
      C in yields ranging from 50% (for typical aliphatic aldehydes) to up to 97% (for
      aromatic aldehydes) using 5 x 10(-3) to 1 mol % of the Pd catalyst. NMR
      spectroscopic study indicated that a sigma-allylpalladium intermediate was formed
      and possibly functions as the nucleophilic species that undergoes addition to the
      aldehydes.

PMID- 16808534
TI  - 1,4-asymmetric induction in methoxyselenenylation of double bonds at the nitrogen
      side of chiral perhydro-1,3-benzoxazines promoted by nonbonded Se...N
      interactions.
AB  - Regio- and diastereoselective methoxyselenenylation of cinnamylamines attached to
      a chiral perhydrobenzoxazine occurs in high yields by reaction with
      benzeneselenenyl chloride in dichloromethane-methanol. The diastereoselection is
      dependent on the temperature of the reaction and the structure of the substituent
      at C-2 and can be rationalized by accepting a 1,4-asymmetric induction process
      after coordination of the selenium to the nitrogen atom of the allylamine system.

PMID- 16808536
TI  - Novel and efficient syntheses of (-)-methyl 4-epi-shikimate and 4,5-epoxy-quinic
      and -shikimic acid derivatives as key precursors to prepare new analogues.
AB  - We have developed simple methods that provide a rapid entry into the synthesis of
      a series of quinate and shikimate analogues, including (-)-methyl 4-epi-shikimate
      and the 4,5-epoxy analogues of the parent acids. Epoxy derivatives of quinic and
      shikimic acids were converted into methyl scyllo-quinate and (+)-methyl 3-epi
      shikimate, respectively, by processes involving a regio- and stereoselective
      epoxide ring opening. The strategies described take place through short, high
      yield reaction sequences.

PMID- 16808535
TI  - Regioselective protection at N-2 and derivatization at C-3 of indazoles.
AB  - Indazoles are regioselectively protected at N-2 by a 2
      (trimethylsilyl)ethoxymethyl (SEM) group using novel conditions. The SEM group
      can efficiently direct regioselective C-3 lithiation, and the resulting
      nucleophile can react with a wide range of electrophiles to generate novel
      indazole derivatives. The SEM group can be removed by treatment with TBAF in THF
      or aqueous HCl in EtOH.

PMID- 16808537
TI  - Microwave-assisted copper-catalyzed preparation of diaryl chalcogenides.
AB  - Diaryl chalcogenide synthesis employing diaryl dichalcogenides and aryl halides
      as starting materials in the presence of excess magnesium and a catalytic amount
      of CuI/bipyridyl is significantly improved by microwave heating. Reaction times
      can be reduced from 2 to 3 days to 6-8 h. Both aryl bromides and aryl chlorides
      can be used as substrates in the substitution reaction. The procedure is useful
      not only for diaryl sulfide and diaryl selenide synthesis but also for the
      preparation of unsymmetrical diaryl tellurides. Starting from suitable aryl
      halides, the novel microwave-assisted procedure was used for the facile
      preparation of novel chalcogen analogues (PhS-, PhSe-, and PhTe-) of various
      antioxidants (ethoxyquin and 3-pyridinol). Attempts to use dialkyl
      dichalcogenides for the coupling of alkylchalcogeno moieties to aryl halides were
      only successful in the case of long-chain (such as n-octyl) disulfides and
      diselenides.

PMID- 16808538
TI  - Synthesis of unique cagelike thiacalix[4]arene derivatives in a 1,3-alternate
      conformation.
AB  - A novel type of doubly bridged thiacalix[4]arenes in the 1,3-alternate
      conformation has been prepared by direct aminolysis reaction of easily accessible
      thiacalix[4]arene tetraacetates with alpha,omega-diamines. Despite the high
      excess of diamine, both sites of a 1,3-alternate conformer can be
      intramolecularly bridged to form the cagelike structures in high yields. Optimum
      results were obtained using 1,2-ethanediamine as bridging units. X-ray analysis
      of the novel cagelike molecules revealed a highly preorganized array of -C(O)-NH-
      bonds pointing to the interior of the cavity.

PMID- 16808539
TI  - Organocatalytic asymmetric deconjugative Michael additions.
AB  - The organocatalytic allylic C-C bond-forming addition of activated alkylidenes to
      acrolein has been achieved with good yield and regio- and enantioselectivity.
      Chiral tertiary amines in the form of cinchona alkaloid catalysts are used to
      give allyl intermediates that exhibit unusual alpha-selectivity in the C-C bond
      forming step. The products are transformed into a large range of intermediates
      that are difficult to access via alternative methods, using different oxidative
      and reductive protocols.

PMID- 16808540
TI  - JOC Recent Reviews, Number 81.
AB  - Reviews are listed in order of appearance in the sources indicated. In
      multidisciplinary review journals, only those reviews which fall within the scope
      of this Journal are included. Sources are listed alphabetically in three
      categories: regularly issued review journals and series volumes, contributed
      volumes, and other monographs. Titles are numbered serially, and these numbers
      are used for reference in the index. Major English-language sources of critical
      reviews are covered. Encyclopedic treatises, annual surveys such as Specialist
      Periodical Reports, and compilations of symposia proceedings are omitted. This
      installment of Recent Reviews covers principally the early part of the 2006
      literature. Previous installment: J. Org. Chem. 2006, 71(7), 2926-34.

PMID- 16808542
TI  - Safety profile of sublingual immunotherapy.
AB  - Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years
      ago with the main aim of improving the safety and avoiding the adverse effects of
      traditional treatment for allergic airways disease. To date, 32 randomized
      controlled trials and 6 postmarketing surveys have been published that provide a
      robust documentation of the safety profile of the treatment.Looking at the
      randomized trials it emerges that the more frequent adverse event of SLIT is oral
      itching or swelling, followed by gastrointestinal complaints. These adverse
      events are invariably described as mild and easily managed by adjusting the dose.
      Relevant systemic adverse events (asthma, urticaria, angioedema) occur
      sporadically and, with the exception of oral/gastrointestinal adverse events, the
      incidence of adverse events seems not to differ between the placebo and active
      groups. The safety profile of SLIT does not differ between adults and
      children.The postmarketing surveys consistently show that the incidence of
      adverse events associated with SLIT is less than 10%, corresponding to less than
      1 adverse event per 1000 doses, and is thus quite superior to the safety profile
      of subcutaneous immunotherapy. Of note, the most recent data show that the rate
      of adverse events with SLIT is not increased in children below the age of 5
      years.

PMID- 16808543
TI  - Improving Health-Related Quality of Life in Patients with Obstructive Sleep Apnea
      : What are the Available Options?
AB  - Obstructive sleep apnea (OSA) syndrome is a common and often life-altering sleep
      related breathing disorder. It not only adversely affects cardiovascular health,
      but the quality of life of these patients is also often significantly
      compromised. They experience excessive daytime sleepiness and poor cognitive,
      social and exercise performance. Furthermore, they often have marital problems
      with increased divorce rates, depression, and poor job performance.Our purpose in
      writing this review is to highlight the various neuropsychiatric domains that are
      affected in OSA patients and to emphasize that identifying and treating this
      condition can significantly improve the quality of life of these individuals. In
      recent years there has been ample evidence supporting the role of treatment for
      OSA to improve cardiovascular outcomes. We provide similar evidence supporting
      the treatment of OSA to improve health-related quality of life outcomes for these
      patients. Surgical, non-surgical and pharmacologic modalities are currently
      available as effective options for the treatment of OSA, with continuous positive
      airway pressure therapy appearing to be the most promising.

PMID- 16808544
TI  - Pharmacodynamic and pharmacokinetic considerations in choosing an inhaled
      corticosteroid.
AB  - Inhaled corticosteroids are effective in controlling airway inflammation. Their
      anti-inflammatory effect is primarily topical, at the site of deposition in the
      airways. Consequently, traditional pharmacodynamic and pharmacokinetic concepts,
      which rely on measuring blood concentrations of drug, have limited applicability
      for evaluating the efficacy of topically acting inhaled corticosteroids.
      Important factors affecting efficacy of inhaled corticosteroids are: (i)
      intrinsic properties of the drugs, particularly their affinity for the
      corticosteroid receptor; and (ii) the newer pharmacodynamic concept of deposition
      characteristics of the drug formulation. Small particle formulations, especially
      those developed in the metered-dose inhaler with the new hydrofluoroalkane
      propellant, deposit to a much greater extent in the lung and may consequently
      have improved clinical efficacy. Lipid conjugation of inhaled corticosteroids
      within the lung may allow prolonged duration of effect, enabling once-daily
      administration. Pharmacodynamic and pharmacokinetic principles probably do not
      play a role in describing upper airway adverse effects occurring with inhaled
      corticosteroids. These are probably also determined by intrinsic properties of
      the drug and deposition characteristics. However, pharmacodynamic and
      pharmacokinetic principles seem to be important in addressing systemic safety
      concerns with inhaled corticosteroids. Those inhaled corticosteroids with a
      longer serum half-life, especially if they have higher affinity for the
      corticosteroid receptor, may be associated with greater systemic effects. A new
      pharmacokinetic concept suggests that increased protein binding within the
      systemic circulation and high systemic clearance of an inhaled corticosteroid may
      reduce the risk for systemic effects. These new pharmacodynamic and
      pharmacokinetic concepts provide a useful framework for identifying the
      characteristics of an inhaled corticosteroid with an improved benefit-to-risk
      profile. Increased lung deposition and reduced deposition in the upper airway
      should result in an inhaled corticosteroid with favorable clinical efficacy and a
      decreased risk for topical upper airway adverse effects. An inhaled
      corticosteroid with high plasma protein binding and rapid clearance might pose
      much less risk for systemic adverse effects than currently available drugs in
      this class.

PMID- 16808545
TI  - Antimicrobial therapy in childhood asthma and wheezing.
AB  - There is an increasing number of viral and bacterial pathogens suspected of
      contributing to asthma pathogenesis in childhood, making it more difficult for
      the practitioner to make specific therapy decisions. This review discusses the
      role of viruses, e.g. respiratory syncytial virus, human metapneumovirus,
      influenza viruses and rhinoviruses, as well as the role of the atypical bacteria
      Chlamydophila pneumoniae and Mycoplasma pneumoniae, as contributors to childhood
      asthma. Diagnosis, prevention, and therapy are discussed, including a summary of
      drugs, i.e. macrolide antibacterials, antivirals, and vaccine regimens already
      available, or at least in clinical trials. For the practitioner dealing with
      patients every day, drug regimens are assigned to the individual pathogens and an
      algorithm for the management of atypical infections in patients with asthma or
      recurrent wheezing is presented.

PMID- 16808546
TI  - Present and future treatment strategies for pulmonary arterial hypertension :
      focus on phosphodiesterase-5 inhibitors.
AB  - Idiopathic pulmonary arterial hypertension (IPAH) is a rare progressive disorder
      historically associated with mortality in <3 years post-diagnosis. The etiology
      of PAH is complex, multifactorial, and likely involves the interplay between
      genetic and environmental factors. These are reviewed with emphasis on the nitric
      oxide pathway. Use of treatment modalities including vasodilator therapy have
      resulted in improved symptoms, hemodynamics, and survival in these patients.
      Vasodilators, including the calcium channel antagonists, prostanoids, and
      endothelin receptor antagonists, have been used to counteract potential
      imbalances in vasoactive mediators in PAH patients; all have produced improved
      long-term symptomatology and hemodynamics. Only the prostanoid epoprostenol has
      improved survival in IPAH patients. Although these medications have worked well
      in many patients with PAH, each of them has limitations. The phosphodiesterase-5
      (PDE-5) inhibitors are a relatively new form of treatment for PAH. They are
      designed to potentiate the effects of cyclic guanosine monophosphate, thereby
      mimicking endogenous nitric oxide within the vasculature. PDE-5 inhibitors are
      selective pulmonary vasodilators effective in animal models of pulmonary
      hypertension. The published clinical studies evaluating their use have been small
      in size to date but appear to demonstrate benefit. The recently completed 12-week
      randomized placebo-controlled Sildenafil Use in Pulmonary Hypertension (SUPER-1)
      trial demonstrated improvement in 6-minute walk distance and hemodynamics in
      patients receiving sildenafil. These data suggest that the PDE-5 inhibitors are
      effective in treating PAH and that it is likely that their usage will increase
      over time. The purpose of this review is to present a current view of the
      pathogenesis and treatment of PAH, with an emphasis on the use of PDE-5
      inhibitors in these patients.

PMID- 16808547
TI  - Evaluating Diagnosis and Treatment Patterns of COPD in Primary Care.
AB  - OBJECTIVE: Many patients with COPD are misdiagnosed or under-treated. The
      characteristics of COPD patients and the patterns of treatment have not been well
      characterized in primary care settings. The objective of this study was to
      identify patterns of COPD onset, diagnosis and treatment with the goal of
      facilitating appropriate treatment at earlier stages. METHODS: A national
      electronic medical record database was used to identify patients with at least a
      6-month history prior to a diagnosis of COPD (ICD-9 codes 491.xx, 492.xx, and
      496). Pulmonary function test (PFT) results closest to the first diagnosis of
      COPD were evaluated to characterize disease severity using the Global Initiative
      for Chronic Obstructive Lung Disease (GOLD) criteria. Prescription data were
      evaluated at the time of diagnosis. All descriptive statistics were conducted
      using STATA statistical software. RESULTS: A total of 14 691 patients met the
      study criteria. Prescription data were available for 9354 (64%) of these
      patients. Of this group, only slightly over 50% (n = 5264) had a respiratory
      related prescription on the date of diagnosis. For those not having a respiratory
      drug at the time of diagnosis, the average time between diagnosis and the first
      respiratory-related prescription was 106 (SD +/- 256.4) days. Only 389 (<3%)
      patients had any PFT data recorded on or prior to the day of their first
      diagnosis of COPD, and only 273 (2%) had sufficient PFT data available to
      determine their GOLD severity class. The average time between diagnosis and first
      COPD prescription was greatest for patients in the lowest severity category
      (Class 0/I; 163 +/- 288.2 days), and smallest for patients in the highest
      severity category (Class IV; 124 +/- 152.3 days). CONCLUSION: COPD is often not
      diagnosed or treated until the later stages of disease, and spirometry is not
      used routinely to diagnose, stage or guide treatment decisions.

PMID- 16808548
TI  - Desmopressin : safety considerations in patients with chronic renal disease.

PMID- 16808549
TI  - Use of the dose, time, susceptibility (DoTS) classification scheme for adverse
      drug reactions in pharmacovigilance planning.
AB  - In the process of conceiving a pharmacovigilance plan, as proposed in the
      International Conference on Harmonisation E2E guideline, the challenge will be
      how to address possible safety issues with a set of appropriate pharmacovigilance
      methods. For successful planning, the various and sometimes complex dimensions of
      the adverse drug reaction in question have to be appropriately described. In
      order to accommodate these better, a 3-dimensional approach, based on dose, time
      and patient susceptibility, has recently been proposed (the DoTS model). This
      approach offers a way of presenting the various dimensions of the problem
      graphically. The aim of this article is to propose how an extended DoTS model,
      applied to three different scenarios, could give a better understanding of
      adverse drug reactions and assist in preparing a pharmacovigilance plan.

PMID- 16808550
TI  - Heart failure induced by non-cardiac drugs.
AB  - Although heart failure is predominantly caused by cardiovascular conditions such
      as hypertension, coronary heart disease and valvular heart disease, it can also
      be an adverse reaction induced by drug therapy. In addition, some drugs have the
      propensity to adversely affect haemodynamic mechanisms in patients with an
      already existing heart condition. In this article, non-cardiac drugs known to be
      associated with the development or worsening of heart failure are reviewed.
      Moreover, drugs that may adversely affect the heart as a pump without causing
      symptoms or signs of heart failure are also included. The drugs discussed include
      anticancer agents such as anthracyclines, mitoxantrone, cyclophosphamide,
      fluorouracil, capecitabine and trastuzumab; immunomodulating drugs such as
      interferon-alpha-2, interleukin-2, infliximab and etanercept; antidiabetic drugs
      such as rosiglitazone, pioglitazone and troglitazone; antimigraine drugs such as
      ergotamine and methysergide; appetite suppressants such as fenfulramine,
      dexfenfluramine and phentermine; tricyclic antidepressants; antipsychotic drugs
      such as clozapine; antiparkinsonian drugs such as pergolide and cabergoline;
      glucocorticoids; and antifungal drugs such as itraconazole and amphotericin B.
      NSAIDs, including selective cyclo-oxygenase (COX)-2 inhibitors, are included as a
      result of their ability to cause heart disease, particularly in patients with an
      already existing cardiorenal dysfunction. Two drug groups are of particular
      concern. Anthracyclines and their derivatives may cause cardiomyopathy in a
      disturbingly high number of exposed individuals, who may develop symptoms of
      insidious onset several years after drug therapy. The risk seems to encompass all
      exposed individuals, but data suggest that children are particularly vulnerable.
      Thus, a high degree of awareness towards this particular problem is warranted in
      cancer survivors subjected to anthracycline-based chemotherapy. A second group of
      problematic drugs are the NSAIDs, including the selective COX-2 inhibitors. These
      drugs may cause renal dysfunction and elevated blood pressure, which in turn may
      precipitate heart failure in vulnerable individuals. Although NSAID-related
      cardiotoxicity is relatively rare and most commonly seen in elderly individuals
      with concomitant disease, the widespread long-term use of these drugs in risk
      groups is potentially hazardous. Pending comprehensive safety analyses, the use
      of NSAIDs in high-risk patients should be discouraged. In addition, there is an
      urgent need to resolve the safety issues related to the use of COX-2 inhibitors.
      As numerous drugs from various drug classes may precipitate or worsen heart
      failure, a detailed history of drug exposure in patients with signs or symptoms
      of heart failure is mandatory.

PMID- 16808552
TI  - Clinical safety of inhaled corticosteroids for asthma in children: an update of
      long-term trials.
AB  - Inhaled corticosteroids are established as the mainstay of maintenance therapy
      for chronic asthma. However, there remains some debate regarding the safety of
      long-term use of these agents, particularly in children. This concern mainly
      stems from the findings of short-term studies assessing the effects of inhaled
      corticosteroids on lower leg growth rate or the hypothalamic-pituitary-adrenal
      axis. However, the clinical relevance of these findings to long-term treatment is
      unknown and significant uncertainty exists regarding the predictive value of
      changes in cortisol levels and clinically relevant changes in growth or bone
      mineral density. To assess the safety of long-term use of inhaled corticosteroids
      in children with asthma, a systematic review of the literature was performed
      focusing on randomised, controlled studies of >or=12 months' duration, to obtain
      data with maximum relevance to clinical practice. Specific searches were
      conducted to identify studies examining each of the following three areas:
      growth, bone mineral density and cortisol levels. Fourteen studies met the
      inclusion criteria for statural growth, four for bone mineral density, and ten
      for cortisol levels. There was some evidence of a small decrease in statural
      growth during the initial period of inhaled corticosteroid therapy. This effect
      was more marked at daily doses of >200 microg and did not apply to all treatment
      regimens. Studies examining final attained adult height found no difference
      between patients treated with inhaled corticosteroids and those receiving
      nonsteroidal therapy. None of the studies investigating effects on bone mineral
      density found any adverse effects of inhaled corticosteroid therapy. Finally,
      recommended doses of inhaled corticosteroids generally had little or no effect on
      plasma- or urinary-cortisol levels versus nonsteroidal therapy. In conclusion,
      this literature review supports the theory that recommended doses of inhaled
      corticosteroids can be administered to children for the long-term management of
      asthma with minimal risk of clinically relevant adverse effects on growth, bone
      density or cortisol levels.

PMID- 16808551
TI  - Second-generation antipsychotics: is there evidence for sex differences in
      pharmacokinetic and adverse effect profiles?
AB  - Six second-generation antipsychotics (SGAs), aripiprazole, clozapine, olanzapine,
      quetiapine, risperidone and ziprasidone, are currently US FDA approved. The aim
      of this review is to investigate whether sex differences exist for efficacy and
      adverse effects of these drugs.Sex-related differences have been shown in the
      pharmacokinetics of cytochrome P450 (CYP), with a higher activity in females for
      CYP3A4 and CYP2D6. However, even if there are pharmacokinetic differences between
      females and males, significantly higher plasma concentrations in women have been
      demonstrated only for olanzapine and clozapine. To date, sex differences in
      adverse effects have not been well studied, but some adverse effects such as
      weight gain, hyperprolactinaemia and cardiac effects are reported to be
      particularly problematic for women. Most of the studies reviewed indicate that
      clozapine and olanzapine are associated with greater bodyweight gain than the
      other atypical antipsychotics, and that serious adverse effects such as metabolic
      syndrome, which includes increased visceral adiposity, hyperglycaemia,
      hypertension and dyslipidaemia induced by SGAs, are more frequent in females.
      According to most studies, the risk for cardiac adverse effects induced by SGAs
      is the same in male and female patients. Although women are at a lower risk of
      sudden cardiac death, they have a higher risk of induced long QT syndrome from
      antiarrhythmic and, probably, antipsychotic drugs. The propensity of sexual
      dysfunctions is higher with conventional antipsychotics than with SGAs.
      Additionally, there is some evidence that female sexual dysfunction is associated
      with high prolactin levels; however, whether the degree of prolactin level
      elevation is different between female and male patients remains controversial.
      There is no evidence for sex differences for any of the SGAs to cause a higher
      rate of extrapyramidal symptoms, acute dystonia or any other movement
      disturbance. Knowledge of the risks and benefits associated with the use of SGAs
      during pregnancy and lactation is limited, although the direction of dose
      adjustments during pregnancy depends on the drug and the enzyme that is
      responsible for its metabolism. In general, data on sex differences were mostly
      obtained by posthoc analysis and, therefore, the conclusions that can be drawn
      are limited. For a better understanding of the basic mechanisms of sex
      differences, future studies with a primary focus on this topic are required. Data
      that are more specific will help determine the extent to which these differences
      will have implications for clinical management.

PMID- 16808553
TI  - Increase in nonfatal digestive perforations and haemorrhages following
      introduction of selective NSAIDs: a public health concern.
AB  - BACKGROUND AND OBJECTIVE: This article documents the impact of the introduction
      of selective NSAIDs on overall prescription patterns of NSAIDs and associated
      gastroprotective agents (GPAs), and on the rate of nonfatal digestive
      perforations and haemorrhages. METHODS: A retrospective, closed cohort study was
      conducted using the Quebec Health Insurance Board databases, for a 3-year period
      overlapping the introduction of selective NSAIDs. All adult subjects who were
      continuously registered with the Public Prescription Drug Program (PPDP) between
      1 January 1999 and 31 December 2001 (n = 2 052 231) were included. Prescriptions
      for NSAIDs (selective [celecoxib, rofecoxib and meloxicam] and nonselective),
      concomitant use of GPAs and nonfatal digestive perforations or haemorrhages
      diagnosed in hospital were compiled. Data were analysed on an annual basis
      according to age, sex and patient risk of gastrointestinal (GI) complications.
      RESULTS: The listing of selective NSAIDs in the PPDP formulary was followed by a
      28.2% increase in the prevalence of NSAID use from 19.5% in 1999 to 25% in 2001.
      The proportion of long-term users also evolved rapidly with a 135% increase over
      3 years. From 1999 to 2001, there was a 75.9% increase in the rate of nonfatal
      digestive perforations and haemorrhages in the presence of NSAIDs. CONCLUSION:
      The introduction of selective NSAIDs stimulated NSAID use and coincided with an
      increased incidence of nonfatal digestive perforations and haemorrhages in the
      presence of NSAIDs. Selective NSAIDs should be prescribed with caution to persons
      at risk for GI complications.

PMID- 16808554
TI  - Temporal relationship between use of NSAIDs, including selective COX-2
      inhibitors, and cardiovascular risk.
AB  - BACKGROUND AND OBJECTIVE: The search for NSAIDs with less gastrointestinal
      toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2)
      inhibitors. However, following their introduction into the market, concerns have
      developed regarding their safety, particularly their cardiovascular safety. The
      purpose of this study was to assess the cardiovascular risk (events included were
      myocardial infarction, stroke and myocardial infarction-related deaths)
      associated with long-term (>180 days of exposure) and short-term (<or=180 days of
      exposure) use of non-selective NSAIDs, including 'preferential COX-2 inhibitors'
      (i.e. etodolac, nabumetone and salsalate), and selective COX-2 inhibitors.
      METHODS: A retrospective analysis of the Veterans Integrated Service Network 17
      Veterans Affairs (VA) database was conducted. Medicare data and Texas Department
      of Health mortality data were incorporated to capture events occurring outside
      the VA healthcare network. Patients >or=35 years of age who received celecoxib,
      rofecoxib, ibuprofen, etodolac and naproxen from 1 January 1999 through 31
      December 2001, were included. Multivariate Cox proportional hazard models were
      used to analyse the relationship between cardiovascular risk and NSAID use,
      including selective COX-2 inhibitor use, while adjusting for various risk
      factors. RESULTS: We identified 12 188 exposure periods (11 930 persons) and 146
      cardiovascular events over the entire study period. Compared with long-term
      ibuprofen use, long-term use of celecoxib (adjusted hazard ratio [HR] 3.64; 95%
      CI 1.36, 9.70) and rofecoxib (adjusted HR 6.64; 95% CI 2.17, 20.28) was
      associated with a significant increase in cardiovascular risk. When restricted to
      patients >or=65 years of age, the cardiovascular risks associated with long-term
      celecoxib (adjusted HR 7.36; 95% CI 1.62, 33.48) and rofecoxib (adjusted HR
      13.24; 95% CI 2.59, 67.68) use increased. Short-term use of celecoxib (adjusted
      HR 0.75; 95% CI 0.42, 1.35) and rofecoxib (adjusted HR 0.85; 95% CI 0.39, 1.86)
      was not associated with any significant change in cardiovascular risk when
      compared with short-term ibuprofen use. Neither long- nor short-term exposure to
      naproxen and etodolac was associated with cardionegative or cardioprotective
      effects when compared with ibuprofen use. CONCLUSIONS: The findings of this
      observational study, along with recent clinical trial results, suggest that
      prolonged exposure to selective COX-2 inhibitors may be associated with an
      increased risk of adverse cardiovascular outcomes.

PMID- 16808555
TI  - Safety of inhalation of a 50% nitrous oxide/oxygen premix: a prospective survey
      of 35 828 administrations.
AB  - BACKGROUND: A 50% nitrous oxide/oxygen (N(2)O/O(2)) premix is widely used to
      alleviate pain or anxiety during brief care procedures in various medical
      domains. In some countries, recent changes in regulation status for medical gases
      state that they should be considered as drugs. Consequently, more valuable data
      gained from exhaustive clinical surveys are needed. This prospective study,
      conducted in the same conditions imposed for testing a drug, aims to analyse the
      factors that affect tolerance of the 50% N(2)O/O(2) premix in a wide range of
      clinical indications. METHODS: In a 4-year prospective survey, 35 942 data sheets
      were received from 191 French hospital paediatric (82%) and adult units (18%). Of
      these, 35 828 sheets were sufficiently complete to be included in the study. The
      number and the type of adverse events declared to the manufacturer were analysed.
      RESULTS: A total of 1581 (4.4%) adverse events were reported on 1384 data sheets,
      which were mostly gastrointestinal and neuropsychiatric disorders (86%). The main
      factors associated with adverse events were age, concomitant drug administration
      and longer duration of inhalation. Among the 27 (0.08%) reported serious adverse
      events, only 9 (0.03%) were possibly attributed to the N(2)O/O(2) premix. Among
      the serious adverse events that were not attributed to the gas, a concomitant
      drug association and insufficient patient surveillance occurred in 12 and 2
      cases, respectively. CONCLUSION: This survey confirms the pharmacological safety
      of the 50% N(2)O/O(2) premix in a wide variety of clinical indications and
      emphasises the need for rational training of medical personnel in its
      administration.

PMID- 16808556
TI  - A survey of the knowledge, attitude and practice of adverse drug reaction
      reporting by clinicians in eastern India.

PMID- 16808557
TI  - Stresses at the cranial base induced by rapid maxillary expansion.
AB  - OBJECTIVE: An analysis of the distribution of stresses at the juvenile and adult
      cranial base after implementation of a rapid palatal suture expansion was the
      goal of this study. Of particular interest were stresses occurring near the
      cranial foramina containing vulnerable structures. MATERIALS AND METHODS: The
      stresses were simulated and analyzed using a finite elements model of the human
      cranial base. The model consisted of several skull bones (sphenoid, frontal bone,
      occipital bone, and the two temporal bones) with a total of 41,556 finite
      elements. To illustrate the differences between reactions in the juvenile and the
      adult, the differing bone elasticity was depicted as variations in the modulus of
      elasticity. RESULTS: At the juvenile cranial base only moderate stresses occurred
      during rapid palatal suture expansion, apparently precluding the likelihood of
      any serious complications in the area of the foramina. The situation in the
      adult, however, was different. Because of the reduced elasticity of the bony
      structures, considerable stress already occurred on light bending of the
      pterygoid process, especially in the area of the round foramen, the oval foramen,
      and the superior orbital fissure, all of which might lead to microfractures with
      injury of nervous and vascular structures. CONCLUSIONS: The lower the bone
      elasticity on carrying out a rapid palatal suture expansion, the more important
      safety measures are for protecting the cranial base. For this reason the
      pterygomaxillary connection should be severed on both sides in adults when
      carrying out a surgically assisted palatal suture expansion.

PMID- 16808558
TI  - Objective measures as indicators for facial esthetics in white adolescents.
AB  - The objective of this study was to examine the contribution of objective measures
      representing anterior-posterior and vertical characteristics, dental esthetics,
      or their combination that are used in daily orthodontic practice in the
      assessment of facial esthetics. A panel of 78 laymen evaluated facial esthetics
      of 32 boys and 32 girls, stratified over the four Angle classes, on a visual
      analogue scale. The relation between the objective parameters and facial
      esthetics was evaluated by backward multiple regression analysis. Dental
      esthetics as expressed by the Aesthetic Component of the Index of Orthodontic
      Treatment Need (AC/IOTN) appeared to be the most important indicator for facial
      esthetics. A new parameter, the "horizontal sum" was found to be a reliable
      variable for the anterior-posterior characteristics of the patient. Addition of
      this newly defined parameter to the AC/IOTN improved the prognostic value from
      25% to 31%.

PMID- 16808559
TI  - Attractiveness of variations in the smile arc and buccal corridor space as judged
      by orthodontists and laymen.
AB  - OBJECTIVE: To evaluate changes in attractiveness on the basis of computerized
      variations of smile arcs and buccal corridors for male and female smiles judged
      by orthodontists and laypersons. MATERIALS AND METHODS: Using a visual analog
      scale in a Web-based survey, orthodontists and laypersons rated the
      attractiveness of nine digitally altered smile arc and buccal corridor variations
      of male and female smiles. The variations were accomplished in a clinically
      relevant manner and based on standards set by experienced orthodontists in a
      pilot web-based survey. RESULTS: The results indicate that both laypersons and
      orthodontists prefer smiles in which the smile arc parallels the lower lip and
      buccal corridors are minimal. Significantly lower attractiveness ratings were
      found for smiles with flat smile arcs and excessive buccal corridors. Flattening
      of the smile arc overwhelms the deleterious effects of excessive buccal corridors
      on attractiveness ratings. CONCLUSIONS: On the basis of the results of this
      study, care should be taken not to produce an excessively flat smile arc during
      orthodontic treatment.

PMID- 16808560
TI  - Phenotypic characterization of Class III patients.
AB  - OBJECTIVE: The objective of this study is to characterize the convergences of
      dentofacial form of skeletal Class III malocclusion in individuals to test the
      fundamental hypothesis that there are distinct subtypes of Class III
      malocclusion. MATERIALS AND METHODS: A detailed phenotypic characterization was
      performed on a retrospective cohort of 309 subjects using cluster and principal
      component analyses on 67 cephalometric variables. RESULTS: The results indicated
      that there are five clusters representing distinct subphenotypes. The principal
      component analysis suggested that the groupings of variables reflect
      anteroposterior and vertical dimensions rather than specific craniofacial
      structures. This may ultimately suggest that different genes are involved in
      controlling dimension vs structures. CONCLUSIONS: Our phenotypic dissection of
      Class III malocclusion established distinct subtypes in a large sample of
      patients and will ultimately provide the basis for future familial studies to
      identify a causative gene.

PMID- 16808561
TI  - Relapse tendency after orthodontic correction of upper front teeth retained with
      a bonded retainer.
AB  - OBJECTIVE: To investigate the amount and pattern of relapse of maxillary front
      teeth previously retained with a bonded retainer. MATERIALS AND METHODS: The
      study group consisted of 135 study casts from 45 patients. Recordings from study
      models before treatment (T1), at debonding (T2), and 1 year after removal of the
      retainer (T3) were present. All patients had been treated with fixed edgewise
      appliances. The irregularity index (sum of contact point displacement [CPD]) and
      rotations of front teeth toward the raphe line were calculated at T1, T2, and T3.
      RESULTS: The mean irregularity index at T1 was 10.1 (range 3.0-29.9, SD 5.4). At
      T2 it was 0.7 (range 0.0-2.1, SD 0.7), and at T3 it was 1.4 (range 0.0-5.1, SD
      1.2). Fifty-five teeth in 42 patients were corrected more than 20 degrees between
      T1 and T2 (mean correction 31.4 degrees range 20.0-61.7), and mean relapse in
      this group was 7.3 degrees (range 0.0-20.5). Regarding alignment of the maxillary
      front teeth, the contact relationship between the laterals and centrals seems to
      be the most critical. A significant positive correlation was found between the
      amount of correction of incisor rotation and the magnitude of relapse but not
      between the amount of correction of CPD and the magnitude of relapse. Eighty-four
      percent of the overcorrected CPDs returned to a desired position. CONCLUSIONS:
      Minor or no relapse was noted at the 1-year follow-up.

PMID- 16808562
TI  - An estimate of craniofacial growth in Class III malocclusion.
AB  - OBJECTIVE: To provide an estimate of growth in Class III malocclusion by means of
      the analysis of a large population of males and females. MATERIALS AND METHODS:
      The examined sample consisted of pretreatment lateral cephalometric records of
      949 (492 females and 457 males) untreated Class III patients of Caucasian
      ancestry. Cephalometric dentoskeletal measurements at subsequent age periods in
      Class III subjects were compared with the population values from subjects
      included in the University of Michigan Growth Study (UMGS) at 11 consecutive age
      periods (from 6 through 16 years of age), in male and female groups separately.
      RESULTS: No difference was found between the Class III and normal groups for the
      sagittal position of the maxilla at any of the age intervals examined. Sagittal
      mandibular position and dimensions in Class III subjects were consistently larger
      than in normal subjects, with the interval of largest "increase" in mandibular
      length occurring on average 1 year later in both female and male Class III
      subject with respect to subjects with normal occlusion. CONCLUSIONS: Increases in
      mandibular length were substantially larger in Class III subjects than in
      subjects with normal occlusion even during the more mature age interval (15 to 16
      years). Lower anterior facial height was significantly larger in Class III
      individuals during the late developmental stages.

PMID- 16808563
TI  - Laterotrusive occlusal schemes and their effect on supra- and infrahyoid
      electromyographic activity.
AB  - The objective of this study was to determine the effects of canine guidance and
      group function on supra- and infrahyoid electromyographic (EMG) activity. The
      sample included 40 healthy subjects, 20 with bilateral canine guidance and 20
      with bilateral group function. Surface electrodes were used to record the
      integrated EMG (IEMG) activity of the left supra- and infrahyoid muscles during
      (1) grinding from intercuspal position to lateral edge-to-edge contact position
      (with canine guidance or group function), (2) static clenching in edge-to-edge
      lateral contact position with canine guidance or group function, and (3) grinding
      from lateral edge-to-edge contact position (with canine guidance or group
      function) to intercuspal position. IEMG activity in the suprahyoid or infrahyoid
      muscles was not significantly different with canine guidance or group function.
      Supra- and infrahyoid IEMG activity in condition 2 was significantly higher than
      in condition 3, which was significantly higher than in condition 1. Supra- and
      infrahyoid IEMG activity was not significantly different with canine guidance and
      group function. Supra- and infrahyoid IEMG activity during the static recording
      (clenching) was significantly higher than during the dynamic recordings
      (grinding). Activity during grinding from the lateral edge-to-edge contact
      position to the intercuspal position was higher than vice versa.

PMID- 16808564
TI  - Functional lateral deviation of the mandible and its positional recovery on the
      rat condylar cartilage during the growth period.
AB  - The objective was to examine the effects of a lateral functional shift of the rat
      mandible and the effects of a shift release on the condylar cartilage during the
      growth period. Fifty 5-week-old male Wistar rats were initially divided into
      three groups: shift, recovery, and control. At 5 weeks of age, each animal in the
      shift and recovery groups received an appliance designed to produce a lateral
      functional shift of the mandible to the left side. For the recovery group, the
      appliance was removed after 2 weeks. For the shift group, the appliance was used
      for 4 weeks. Total cartilage thickness, 5-bromo-2'-deoxyuridine-labeling index,
      and toluidine blue and tartrate-resistant acid phosphatase-positive cell number
      in the condylar cartilage at 1, 2, 3, and 4 weeks were compared with those in age
      matched controls that had no appliances. In the shift group at 2 weeks, the
      cartilage thickness and labeling index increased in the central region on the
      contralateral side, whereas these decreased in the lateral region on the
      ipsilateral side. However, in the recovery group, 1 to 2 weeks after appliance
      removal, the cartilage thickness and labeling index in both investigated regions
      became similar to the control groups. These results emphasize the importance of
      early treatment to normalize occlusion and create appropriate conditions for
      normal occlusal development.

PMID- 16808565
TI  - Matrix metalloproteinase-9 regulates graft bone resorption.
AB  - OBJECTIVE: To explore the relationship between bone resorption and matrix
      metalloproteinase-9 (MMP-9) expression in autogenous and allogenic bone grafts.
      MATERIALS AND METHODS: A total of 18 critical-size (10 x 15 mm) defects were
      created in rabbit mandibles bilaterally. Three groups of six defects each were
      grafted with autogenous endochondral (EC) bone, autogenous intramembranous (IM)
      bone, and allogenic IM bone. Three months later, the defects were retrieved for
      quantitative analysis on the basis of histology, immunohistochemistry, and in
      situ hybridization. RESULTS: A close relationship existed between MMP-9
      expression and graft bone resorption. The parallel between MMP-9 expression and
      graft bone resorption suggested that bone resorption was accomplished in part by
      increased MMP-9 production evident in preosteoclasts and osteoclasts.
      CONCLUSIONS: MMP-9 plays an important role in graft bone resorption. Autogenous
      EC bone grafts express higher levels of MMP-9 leading to more resorption than
      autogenous or allogenic IM bone grafts.

PMID- 16808566
TI  - Accuracy of facial plaster casts.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of facial plaster
      casts and their suitability for 3-D mapping. MATERIALS AND METHODS: All
      measurements were carried out on 15 adult probands (seven female and eight male;
      age range 19-31 years, mean 24.7 years). A plaster cast of the facial surface was
      prepared for all probands using alginate impressions. The plaster casts and the
      probands faces were digitized using a three-dimensional laser-scanner operating
      with structured light. The resulting point clouds were matched in a virtual
      environment to analyze the deviations between the cast and the facial surfaces,
      both qualitatively and quantitatively. RESULTS: The average deviations depended
      on the facial area and lay between 0.95 and 3.55 mm. Marked differences between
      the plaster cast and the facial surface were found, particularly in the area of
      the lips, at the roof of the nose, at the cheeks, and in the entire lower facial
      area. CONCLUSIONS: The regionally exacerbated soft tissue deformations that occur
      during impression of the facial surface lead to inaccuracies in the resulting
      plaster cast that forbids any use for morphometric analysis. Documentation of
      pathological findings in cleft lip and palate using facial plaster casts does
      appear to be justifiable.

PMID- 16808567
TI  - Development of cephalometric norms using a unified facial and dental approach.
AB  - OBJECTIVE: To develop a cephalometric determination of anteroposterior skeletal
      occlusion on the basis of a clinically rational "gold standard" and objectively
      determined cut points. MATERIALS AND METHODS: Pretreatment cephalograms from 10-
      to 18-year-old Caucasian patients with a normal vertical face dimension were
      digitized. Facial profile line drawings were judged by orthodontist raters as
      Class I, II, or III. Subjects who met all inclusion criteria were divided into
      Class I, Class II, and Class III on the basis of the matched skeletal (facial)
      and dental occlusion and comprised our gold standard for anteroposterior skeletal
      occlusions. Cephalometric variables included ANB angle, McNamara analysis,
      Harvold unit differential, anteroposterior dysplasia index (APDI), and Wits
      analysis. Half the sample was used to derive skeletal classification norms using
      receiver operator characteristic (ROC) curves, and half the sample was used to
      test for diagnostic ability and to compare the diagnoses based on traditional
      cephalometric norms with the new norms. RESULTS: Results of the study showed that
      ANB and McNamara analysis performed well with traditional and ROC-derived norms,
      whereas Wits, Harvold unit differential, and APDI showed fewer errors in
      diagnosis with ROC norms compared with traditional norms. CONCLUSIONS: The use of
      a single set of diagnostic norms for each analysis to distinguish between the
      skeletal classifications for the 10- to 18-year-age group proved to be highly
      successful for each of the analyses and performed as well or better than when
      using traditional norms based on age and sex.

PMID- 16808568
TI  - Validity and reliability of a new edge-based computerized method for
      identification of cephalometric landmarks.
AB  - OBJECTIVE: To evaluate the validity and inter- and intraexaminer reliability when
      on-screen landmarks are digitized manually or when these are computer-assisted by
      means of a new cephalometric software feature. MATERIALS AND METHODS: Twenty
      radiographs were digitized four times by two experienced orthodontists using a
      manual method and an edge-based algorithm that helps landmark identification by
      detecting the edges of anatomical structures. RESULTS: The computer-assisted
      method did not agree with manual digitization in 7 of 13 landmarks and 5 of 10
      variables. With a tolerance of 0.5 mm or degrees, the two methods did not agree
      in cephalometric variables. Intraoperator reliability was improved for B point (x
      axis), and Menton (x- and y-axis). It got worse for point A (y-axis).
      Interoperator reliability was improved for B point (x- and y-axis), Soft Labrale
      Inferior (x- and y-axis), Soft Pogonion (x-axis), and Menton (y-axis). It
      decreased for point A (y-axis). Intra- and interoperator reliability got better
      for only one cephalometric variable under study (SNB). CONCLUSIONS: The edge
      locking feature seems to be a promising tool for increasing the reliability of on
      screen cephalometric analysis. There seem to be difficulties in locating the
      appropriate edges when artifacts or soft tissue edges are located near the
      targeted landmark. The existence of very small, but systematic differences
      between the two digitization methods manifests the need for further improvement.

PMID- 16808569
TI  - Sagittal spinal posture in relation to craniofacial morphology.
AB  - OBJECTIVE: The aim of this study is to determine correlations between the
      parameters of body posture in the sagittal profile and sagittal jaw position by
      obtaining objective and valid three-dimensional measurements of the dorsal
      profile by means of rasterstereography. MATERIALS AND METHODS: Fifty-three adults
      with Class II or III malocclusions were examined, and six angular parameters were
      determined. For the sagittal analysis of body posture, the Fleche Cervicale and
      Lombaire as well as trunk inclination were evaluated. RESULTS: Statistically
      significant correlations (P < .05) were found between Facial Axis and Fleche
      Cervicale, Mandibular Plane angle and Fleche Cervicale, and Facial Depth and the
      Fleche Cervicale. CONCLUSIONS: It can be concluded that the mandible seems to
      have a greater effect on body posture than other craniofacial parameters. As a
      clinical result of this study, patients with severe malocclusions should be
      examined interdisciplinarily before orthognathic surgery is performed to minimize
      postural influence on the altered jaw relationship after surgery.

PMID- 16808570
TI  - Tanaka-Johnston mixed dentition analysis for southern Chinese in Hong Kong.
AB  - OBJECTIVE: To compare the prediction of unerupted permanent canine and premolar
      size of a comparable sample size of southern Chinese population with that of the
      study of Tanaka and Johnston. MATERIALS AND METHODS: Teeth on study casts of an
      unselected sample from a 12-year-old Hong Kong Oral Health Survey of 12-year-old
      children (n = 459; 295 males and 164 females) were measured in the mesiodistal
      dimension. A Chinese mixed dentition analysis based on the Tanaka and Johnston
      method was constructed with linear regression equations for prediction of the
      mesiodistal widths of unerupted canines and premolars. RESULTS: Sexual dimorphism
      was evident between southern Chinese males and females in incisors, canines, and
      premolars in the mesiodistal dimension. CONCLUSIONS: To predict the space (in mm)
      required for alignment of unerupted canine and premolars in southern Chinese
      children, halve the sum of the mesiodistal dimensions of the four mandibular
      incisors and add the respective constants for males (upper, 11.5; lower, 10.5) or
      females (upper, 11.0; lower, 10.0).

PMID- 16808571
TI  - Bolton tooth size discrepancies in skeletal Class I individuals presenting with
      different dental angle classifications.
AB  - The objective of this study was to investigate the frequency and association of
      Bolton tooth size discrepancies with dental discrepancies. Forty-eight skeletal
      Class I, 60 Class II, and 44 Class III subjects with similar skeletal
      characteristics were included in this study. Analysis of variance was performed
      to compare the mean ratios of Bolton analysis as a function of the Angle
      classification and sex. To determine the prevalence of tooth size imbalances
      among the three groups of occlusions and the two sexes, chi-square tests were
      performed. To determine the correlation of tooth size imbalances with certain
      dental characteristics, Pearson's correlation coefficients were calculated. No
      statistically significant differences were determined for the prevalence of tooth
      size discrepancies and the mean values of Bolton's anterior and overall ratios
      among the occlusal groups and sexes. Bolton's anterior ratio discrepancies had
      significant correlations with midline shifts (P < .05) in Angle Class I cases,
      with U1-SN angle (P < .01) in Angle Class II cases, and with L1-APog distance (P
      < .05) in Angle Class III cases. Bolton discrepancies related to overall ratio
      had significant correlations with overjet (P < .05) in Class I cases, with
      overbite (P < .05) and U1-SN angle (P < .01) in Class II cases, and with IMPA (P
      < .01) in Class III cases. A high prevalence of tooth size discrepancies in an
      orthodontic patient population and the statistically significant correlation of
      some of these with some dental characteristics suggest that the measurement of
      interarch tooth size ratios might be clinically beneficial for treatment
      outcomes.

PMID- 16808572
TI  - Applicability of three tooth size prediction methods for white Brazilians.
AB  - The objectives of this study were to evaluate the applicability of the methods of
      Moyers; Tanaka and Johnston; and Bernabe and Flores-Mir to Brazilian individuals
      and to propose new regression equations using the lower four permanent incisors
      as predictors for the sum of the widths of the lower permanent canine and
      premolars. Five hundred dental study casts (250 male and 250 female white
      patients) were used. The methods of Moyers and Tanaka and Johnston were tested on
      a sample consisting of 240 female and 223 male patients. The method of Bernabe
      and Flores-Mir and the new regression equations were based on the complete
      sample. At the 50th and 75th percentile levels, Moyers' tables tended to
      underestimate the actual sum of the lower permanent canine and premolars for male
      and female samples, with statistically significant differences. Although the same
      statistical significant differences were found when Tanaka and Johnston's and
      Bernabe and Flores-Mir's methods were used, these differences were not clinically
      relevant. The new regression equations proposed demonstrate similar correlation
      and determination coefficients to those found in other studies based on the lower
      four permanent incisors as predictors. Validating studies (based on similar
      samples) must be conducted to confirm the applicability and precision of the
      proposed new regression equations.

PMID- 16808573
TI  - Maxillary molar distalization with a bone-anchored pendulum appliance.
AB  - To obtain an effective and compliance-free molar distalization without an
      anchorage loss, we designed the bone-anchored pendulum appliance (BAPA). The aim
      of this study was to evaluate the stability of the anchoring screw, distalization
      of the maxillary molars, and the movement of teeth anterior to maxillary first
      molars. The study group comprised 10 patients (mean age 13.5 +/- 1.8 years) with
      Class II molar relationship. A conventional pendulum appliance was modified to
      obtain anchorage from an intraosseous screw instead of the premolars. The screw
      was placed in the anterior paramedian region of the median palatal suture.
      Skeletal and dental changes were measured on cephalograms, and dental casts were
      obtained before and after distalization. A super Class I molar relationship was
      achieved in a mean period of 7.0 +/- 1.8 months. The maxillary first molars
      distalized an average of 6.4 +/- 1.3 mm in the region of the dental crown by
      tipping distally an average of 10.9 degrees +/- 2.8 degrees . Also, the maxillary
      second premolar and first premolar moved distally an average of 5.4 +/- 1.3 mm
      and 3.8 +/- 1.1 mm, respectively. The premolars tipped significantly distally. No
      anterior incisor movement was detected. The BAPA was found to be an effective,
      minimally invasive, and compliance-free intraoral distalization appliance for
      achieving both molar and premolar distalization without any anchorage loss.

PMID- 16808574
TI  - Anchorage effect of osseointegrated vs nonosseointegrated palatal implants.
AB  - Palatal implants can be used with a transpalatal arch (TPA) connected with the
      second premolar to provide anchorage. The purpose of this study was to compare
      the anchorage effects of an osseointegrated palatal implant (OPI) with a
      nonosseointegrated palatal implant (NOPI), using finite element analysis. One
      model, which was composed of two maxillary premolars, periodontal ligament (PDL),
      alveolar bone, a palatal implant, palatal bone, a bracket, band, and TPA, was
      created on the basis of the clinical situation. The palatal implant was treated
      as either NOPI or OPI. The force on the premolars was investigated under three
      conditions: a distomesial horizontal force, a buccolingual horizontal force, and
      a vertical intrusive force. The PDL stress was calculated and compared with a
      model without an implant. The result showed that OPI could reduce PDL stress
      significantly. (The average stress was reduced by 14.44% for the distomesial
      horizontal force, 60.28% for the buccolingual horizontal force, and 17.31% for
      the vertical intrusive force.) The NOPI showed almost the same anchorage effect
      as OPI. The stress on the NOPI surface was higher than that on the OPI surface,
      but the stress was not high enough to result in failure of the implant. These
      results suggested that waiting for osseointegration might be unnecessary for an
      orthodontic implant.

PMID- 16808575
TI  - Forsus Nitinol Flat Spring and Jasper Jumper corrections of Class II division 1
      malocclusions.
AB  - OBJECTIVE: To compare the effects of Forsus Nitinol Flat Spring (FNFS) and Jasper
      Jumper (JJ) in the correction of Class II division I malocclusions. MATERIALS AND
      METHODS: Our research was conducted on 48 adolescents, who had a normal or
      horizontal growth pattern and retrognathic mandible. The patients were divided
      into three equal groups randomly. First group was treated with FNFS, and the
      second group was treated with JJ appliances, whereas the third group was the
      control group. Lateral cephalograms and study models were obtained after the
      leveling phase and at time of the removal of the appliances. RESULTS:
      Cephalometric analysis revealed that both the appliances stimulated mandibular
      growth, increased the anterior face height because of the lower face, and
      elongated the posterior face height because of the growth of temporomandibular
      joint. Maxillary central incisors were extruded, retruded, and distally tipped.
      Contrarily, intrusion, protrusion, and labial tipping were observed in the
      mandibular central incisors. Distal movement and intrusion of the maxillary first
      molars and mesial movement and extrusion of the mandibular first molars were the
      other dental alterations. Overjet and overbite were decreased, and a Class I
      molar relationship and improvement in the profile were attained in both treatment
      groups. Cast model analysis showed expansion in the maxillary and mandibular
      dental arches. CONCLUSIONS: Both the appliances were effective in the treatment
      of Class II malocclusion and revealed nearly same alterations in the skeletal,
      dental, and soft tissue parameters.

PMID- 16808576
TI  - Effects of light-emitting diode and halogen light curing techniques on ceramic
      brackets bonded to porcelain surfaces.
AB  - The objectives of this study were to test the efficiency of LED curing devices in
      bonding ceramic brackets to porcelain surfaces and to compare the effects of LED
      and halogen curing techniques on shear bond strength of ceramic brackets. A total
      of 20 glazed porcelain facets were randomly divided into two groups of 10.
      Porcelain surfaces were etched with 9.6% hydrofluoric acid for 2 minutes, and
      silane was applied on the etched porcelain surface. Ceramic brackets were bonded
      with an LC composite resin cured with soft start mode LED and a halogen light.
      Bond strengths, as determined in the shear mode, were higher in the LED group (P
      < .001). LED curing units with the soft start polymerization mode were more
      effective than halogen curing units in bonding ceramic brackets on porcelain
      surfaces. The type of curing light must be considered as an important factor
      affecting bond strength of ceramic brackets on porcelain surfaces.

PMID- 16808577
TI  - Conventional and high-intensity halogen light effects on polymerization shrinkage
      of orthodontic adhesives.
AB  - The objectives of this study were to compare the polymerization shrinkage of
      three orthodontic adhesives. In addition we wanted to determine the effectiveness
      of the high-intensity quartz tungsten halogen (HQTH) in curing orthodontic
      adhesives on polymerization shrinkage with that of the quartz tungsten halogen
      (QTH). A total of 120 glass ring molds were prepared using a low-speed saw. The
      internal surface of the glass rings were roughened and etched. Adhesive pastes
      were placed into the glass molds, which were sandwiched between two glass slides.
      Samples were divided into six groups according to the combination of three
      orthodontic adhesives (Kurasper F, Light Bond, and Transbond XT) and two light
      intensities. One half of each 40 samples of three adhesive pastes was polymerized
      for 20 seconds by a QTH (Hilux 350), and the other half was polymerized for 10
      seconds by a HQTH (Optilux 501). The volumetric polymerization shrinkage for each
      system was measured through the specific density method modified by Puckett and
      Smith. Statistical analysis was performed using two-way analysis of variance for
      intergroup comparisons. The HQTH-curing unit resulted in a more polymerization
      shrinkage than did the QTH for all investigated adhesives. However, no
      statistically significant differences were found. The highest shrinkage was
      observed for Light Bond cured with HQTH (1.59 +/- 0.82%), and the lowest value
      was observed for Transbond XT cured with QTH (1.23 +/- 0.60%). There are no
      significant differences in polymerization shrinkage of the three investigated
      orthodontic adhesives when polymerized with a QTH or a HQTH.

PMID- 16808578
TI  - Distance and time effect on shear bond strength of brackets cured with a second
      generation light-emitting diode unit.
AB  - OBJECTIVE: The aims of this study were to evaluate increasing exposure times and
      distance between source (light-emitting diode) and adhesive composite on the
      shear bond strength (SBS) of stainless steel brackets. MATERIALS AND METHODS:
      Stainless steel maxillary incisor brackets (3M Unitek, Monrovia, Calif) were
      bonded to the facial surfaces of 120 bovine incisors. The bond of each specimen
      in eight randomly divided groups was tested to failure using an Instron Universal
      Testing Machine (Instron Corp, Canton, Mass). The mode of failure was evaluated
      using the adhesive remnant index (ARI). RESULTS: There were significant SBS
      differences between exposure times; 5-second exposures were significantly less
      than at 20-and 40-second exposures; SBS increased in a curvilinear fashion.
      Significant differences were recorded neither in the frequencies of ARI scores
      nor the SBS in relation to distance. Significant differences in the frequencies
      of ARI scores were observed when comparing the 5-second cure time to other time
      periods, indicating incomplete polymerization in the bracket base. CONCLUSIONS:
      SBS increased with increasing time periods in a curvilinear fashion, with no
      difference between the distances evaluated from source to specimen.

PMID- 16808579
TI  - Shear bond strength and residual adhesive after orthodontic bracket debonding.
AB  - OBJECTIVE: To compare the shear bond strength and determine the area of residual
      adhesive on teeth after the debonding of brackets bonded with two types of
      orthodontic adhesives. These were a resin-modified glass ionomer cement (RMGIC;
      Fuji ORTHO LC, GC Corporation, Tokyo, Japan) and a resin applied as a precoated
      bracket (APC bracket, 3M Unitek GmbH, Seefeld, Germany). MATERIALS AND METHODS: A
      total of 60 premolar teeth were randomly divided into two groups, and brackets
      were bonded according to the manufacturers' instructions. In group 1, the teeth
      were conditioned using 10% polyacrylic acid, and the brackets were bonded using
      Fuji Ortho LC in wet condition. In group 2, the teeth were etched using 37%
      phosphoric acid, and the APC brackets were bonded. Bond strength was measured
      using a testing instrument (2000S, Lloyds Instruments, Fareham, England) at a
      crosshead speed of 1 mm/min, and the residual adhesive was quantified using a
      three-dimensional laser scanning instrument. RESULTS: The Mann-Whitney test
      showed that the median bond strength of group 1 was significantly lower than that
      of group 2 (P < .001). A Pearson chi-square test of the Adhesive Remnant Index
      (ARI) revealed a significant difference among the groups tested. All the
      adhesives in group 1 failed at the enamel/adhesive interface (100%), whereas
      group 2 exhibited cohesive failure of the adhesive (90%). CONCLUSIONS: The bond
      strength values obtained with the RMGIC were above the minimum values suggested
      in the literature to achieve a clinically effective adhesion in orthodontics.

PMID- 16808580
TI  - Metallic brackets bonded with resin-reinforced glass ionomer cements under
      different enamel conditions.
AB  - OBJECTIVE: To assess the shear bond strength of metallic orthodontic brackets
      bonded with either Fuji Ortho or Ortho Glass LC resin-reinforced glass ionomer
      cements to enamel surfaces under different conditions, namely, enamel without
      etching, enamel conditioned with 37% phosphoric acid and enamel conditioned with
      Transbond Plus Self Etching Primer (TPSEP). MATERIALS AND METHODS: One hundred
      and five bovine inferior incisors were divided into seven groups (n = 15). In
      group 1 (control) Transbond XT was used according to the manufacturer's
      recommendations. In groups 2, 3, and 4 all using Fuji Ortho LC, the brackets were
      bonded, respectively, to enamel nonetched, enamel etched with 37% phosphoric
      acid, and enamel etched with TPSEP. In groups 5, 6, and 7, the bonding was
      performed using Ortho Glass LC under the same enamel conditions observed in the
      other experimental groups. After 24 hours, shear bond strength tests were
      performed for all samples at a crosshead speed of 0.5 mm/min. RESULTS: The
      results (MPa) showed no statistically significant difference between groups 1, 3,
      and 4 (P > .05). However, such groups were statistically superior to the others
      (P < .05). No statistically significant difference was observed between groups 2,
      6, and 7 (P > .05). Group 5 showed the lowest shear strength value, which was
      also statistically inferior to the other groups (P < .05). CONCLUSIONS:
      Regardless of the enamel treatment, Fuji Ortho LC yielded shear strength values
      superior to those from Ortho Glass LC.

PMID- 16808581
TI  - Galvanic corrosion behavior of orthodontic archwire alloys coupled to bracket
      alloys.
AB  - The purpose of this study was to provide a quantitative assessment of galvanic
      corrosion behavior of orthodontic archwire alloys coupled to orthodontic bracket
      alloys in 0.9% NaCl solution and to study the effect of surface area ratios. Two
      common bracket alloys, stainless steels and titanium, and four common wire
      alloys, nickel-titanium (NiTi) alloy, beta-titanium (beta-Ti) alloy, stainless
      steel, and cobalt-chromium-nickel alloy, were used. Three different area ratios,
      1:1, 1:2.35, and 1:3.64, were used; two of them assumed that the multibracket
      appliances consists of 14 brackets and 0.016 inch of round archwire or 0.016 x
      0.022 inch of rectangular archwire. The galvanic current was measured for 3
      successive days using zero-impedance ammeter. When the NiTi alloy was coupled
      with Ti (1:1, 1:2.35, and 1:3.64 of the surface area ratio) or beta-Ti alloy was
      coupled with Ti (1:2.35 and 1:3.64 of the surface area ratio), Ti initially was
      the anode and corroded. However, the polarity reversed in 1 hour, resulting in
      corrosion of the NiTi or beta-Ti. The NiTi alloy coupled with SUS 304 or Ti
      exhibited a relatively large galvanic current density even after 72 hours. It is
      suggested that coupling SUS 304-NiTi and Ti-NiTi may remarkably accelerate the
      corrosion of NiTi alloy, which serves as the anode. The different anode-cathode
      area ratios used in this study had little effect on galvanic corrosion behavior.

PMID- 16808582
TI  - Soft tissue changes with fixed functional appliances in Class II division 1.
AB  - OBJECTIVE: To evaluate facial soft tissue changes after the use of fixed
      functional appliances in Class II division 1 malocclusion cases using a
      systematic review of the literature. MATERIALS AND METHODS: Several electronic
      databases (PubMed, Medline, Medline In-Process & Other Non-Indexed Citations,
      Cochrane Database, Embase, Web of Sciences, and Lilacs) were searched with the
      help of a senior Health Sciences librarian. Abstracts that appeared to fulfill
      the initial selection criteria were selected by consensus. The original articles
      were then retrieved. Their references were also hand-searched for possible
      missing articles. Clinical trials assessing facial soft tissue changes with the
      use of fixed functional appliances without any surgical intervention or syndromic
      characteristics were considered. A comparable untreated control group was
      required to factor out normal growth changes. Four articles using Herbst and one
      using Jasper Jumper fulfilled the selection criteria. An individual analysis of
      these articles was made and some methodological flaws were identified. RESULTS:
      Although fixed functional appliances produce some significant statistical changes
      in the soft tissue profile, the magnitude of the changes may not be perceived as
      clinically significant. CONCLUSIONS: The conclusions from this systematic review
      should be considered with caution because only a secondary level of evidence was
      found. Long-term double-blinded prospective randomized clinical trials are
      needed. Three-dimensional quantification of the soft tissue changes is required
      to overcome current limitations in our understanding of the soft tissue changes
      obtained with the use of fixed functional appliances.

PMID- 16808583
TI  - Implant vs screw loading protocols in orthodontics.
AB  - OBJECTIVE: This systematic review presents the loading protocols applied when
      using implants and/or screws in orthodontic treatments. MATERIALS AND METHODS:
      Clinical trials which assessed the use of implants and/or screws for orthodontic
      anchorage and studies involving treatment on syndromic patients, surgery, other
      simultaneous treatments, or appliances (ie mini-plates) were considered.
      Electronic databases (Medline, Medline In-Process & Other Non-Indexed Citations,
      Lilacs, Pubmed, Embase, Web of Science, and All Evidence Based Medicine Reviews)
      were searched with the help of a senior Health Sciences librarian. Abstracts
      which appeared to fulfill the selection criteria were selected by consensus. The
      original articles were then retrieved and evaluated with a methodological
      checklist. References were also hand searched for possible missing articles.
      RESULTS: Eleven articles fulfilled the selection criteria established. Five
      studies involved the use of implants while six involved the use of screws for
      orthodontic purposes. An individual methodological analysis for each article was
      made. CONCLUSIONS: Loading protocols for implants involve a minimum waiting
      period of 2 months before applying orthodontic forces while loading protocols for
      screws involve immediate loading or a waiting period of 2 weeks to apply forces.
      Success rates for implants were on average higher than for screws.

PMID- 16808584
TI  - Severe anterior open-bite malocclusion.
AB  - This case report describes the treatment of a severe anterior open bite, Class II
      malocclusion with a history of dummy sucking. The 9-year-old girl presented with
      a significant anteroposterior and vertical discrepancy. Her face was convex with
      procumbent lips. She had an anterior open bite of 9 mm, an overjet of 8 mm, and a
      transverse maxillary deficiency. In consultation with the parents and patient, a
      nonsurgical therapy was elected, with the goals of reducing protrusion and
      closing the anterior open bite.

PMID- 16808585
TI  - Orthodontic intervention and patients with Down syndrome.

PMID- 16808587
TI  - Re: vertical changes in class II division 1 malocclusion after premolar
      extractions.

PMID- 16808589
TI  - Re: esthetic influence of negative space in the buccal corridor during smiling.

PMID- 16808591
TI  - Early shear bond strength of a one-step self-adhesive on orthodontic brackets.
AB  - OBJECTIVE: The purpose of this study was to determine whether a self-adhesive
      universal cement, RelyX Unicem (3M ESPE, Seefeld, Germany), can be used
      successfully to bond orthodontic brackets to enamel. MATERIALS AND METHODS: Forty
      human molars were cleaned, mounted, and randomly divided into two groups: 20
      orthodontic brackets were bonded to teeth using RelyX Unicem, and 20 brackets
      were bonded using the Transbond XT (3M Unitex, Monrovia, Calif) adhesive system.
      The teeth were debonded within 30 minutes after initial bonding using a universal
      testing machine. After debonding, the enamel surface was examined under 10x
      magnification to determine the amount of residual adhesive remaining on the
      tooth. Student's t-test was used to compare the shear bond strength (SBS) of the
      two groups, and the chi-square test was used to compare the Adhesive Remnant
      Index (ARI) scores for the two adhesive systems. RESULTS: The mean SBS of the
      brackets bonded using the RelyX Unicem was 3.7 +/- 2.1 MPa and was significantly
      lower (t = 2.07, P = .048) than the SBS of the brackets bonded with the Transbond
      system (x = 5.97 +/- 4.2 MPa). The comparisons of the ARI scores between the two
      groups (chi(2) = 17.4) indicated that bracket failure mode was significantly
      different (P = .002) with more adhesive remaining on the teeth bonded with
      Transbond XT. CONCLUSIONS: The SBS of the self-adhesive universal cement needs to
      be increased for it to be successfully used for bonding orthodontic brackets.

PMID- 16808592
TI  - Interstitial fluorescence spectroscopy in the human prostate during motexafin
      lutetium-mediated photodynamic therapy.
AB  - The in vivo fluorescence emission from human prostates was measured before and
      after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). A single side
      firing optical fiber was used for both the delivery of 465 nm light-emitting
      diode excitation light and the collection of emitted fluorescence. It was placed
      interstitially within the prostate via a closed transparent plastic catheter.
      Fitting of the collected fluorescence emission spectra using the known
      fluorescence spectrum of 1 mg/kg MLu in an intralipid phantom yields a
      quantitative measure of the local MLu concentration. We found that an additional
      correction factor is needed to account for the reduction of the MLu fluorescence
      intensity measured in vivo due to strong optical absorption in the prostate. We
      have adopted an empirical correction formula given by C = (3.1 cm(-1)/micro's)
      exp (microeff x 0.97 cm), which ranges from approximately 3 to 16, with a mean of
      9.3 +/-4.8. Using a computer-controlled step motor to move the probe
      incrementally along parallel tracks within the prostate we can determine one
      dimensional profiles of the MLu concentration. The absolute MLu concentration and
      the shape of its distribution are confirmed by ex vivo assay and by diffuse
      absorption measurements, respectively. We find significant heterogeneity in
      photosensitizer concentration within and among five patients. These variations
      occur over large enough spatial scales compared with the sampling volume of the
      fluorescence emission that mapping the distribution in three dimensions is
      possible.

PMID- 16808593
TI  - Singlet oxygen luminescence dosimetry (SOLD) for photodynamic therapy: current
      status, challenges and future prospects.
AB  - As photodynamic therapy (PDT) continues to develop and find new clinical
      indications, robust individualized dosimetry is warranted to achieve effective
      treatments. We posit that the most direct PDT dosimetry is achieved by monitoring
      singlet oxygen (1O2), the major cytotoxic species generated photochemically
      during PDT. Its detection and quantification during PDT have been long-term goals
      for PDT dosimetry and the development of techniques for this, based on detection
      of its near-infrared luminescence emission (1270 nm), is at a noteworthy stage of
      development. We begin by discussing the theory behind singlet-oxygen luminescence
      dosimetry (SOLD) and the seminal contributions that have brought SOLD to its
      current status. Subsequently, technology developments that could potentially
      improve SOLD are discussed, together with future areas of research, as well as
      the potential limitations of this method. We conclude by examining the major
      thrusts for future SOLD applications: as a tool for quantitative photobiological
      studies, a point of reference to evaluate other PDT dosimetry techniques, the
      optimal means to evaluate new photosensitizers and delivery methods and,
      potentially, a direct and robust clinical dosimetry system.

PMID- 16808594
TI  - Photoisomerization in proteorhodopsin mutant D97N.
AB  - The first steps of the photocycle of the D97N mutant of proteorhodopsin (PR) have
      been investigated by means of ultrafast transient absorption spectroscopy. A
      comparison with the primary dynamics of native PR and D85N mutant of
      bacteriorhodopsin is given. Upon photoexcitation of the covalently bound all
      trans retinal the excited state decays biexponentially with time constants of 1.4
      and 20 ps via a conical intersection, resulting in a 13-cis isomerized retinal.
      Neither of the two-deactivation channels is significantly preferred. The dynamics
      is slowed down in comparison with native PR at pH 9 and reaction rates are even
      lower than for native PR at pH 6, where the primary proton acceptor (Asp97) is
      protonated. Therefore, the ultrafast isomerization is not only controlled by the
      charge distribution within the retinal binding pocket. This study shows that in
      addition to direct electrostatics other effects have to be taken into account to
      explain the catalytic function of Asp97 in PR on the ultrafast isomerization
      reaction. This may include sterical interactions and/or bound water molecules
      within the retinal binding pocket.

PMID- 16808595
TI  - Singlet oxygen oxidation of isolated and cellular DNA: product formation and
      mechanistic insights.
AB  - This survey focuses on recent aspects of the singlet oxygen oxidation of the
      guanine moiety of nucleosides, oligonucleotides, isolated and cellular DNA that
      has been shown to be the exclusive DNA target for this biologically relevant
      photogenerated oxidant. A large body of mechanistic data is now available from
      studies performed on nucleosides in both aprotic solvents and aqueous solutions.
      A common process to both reaction conditions is the formation of 8-oxo-7,8
      dihydroguanine by reduction of 8-hydroperoxyguanine that arises from the
      rearrangement of initially formed endoperoxide across the 4,8-bond of the purine
      moiety. However, in organic solvent the hydroperoxide is converted as a major
      degradation pathway into a dioxirane that subsequently decomposes into a complex
      pattern of oxidation products. A different reaction that involved the formation
      of a highly reactive quinonoid intermediate consecutively to the loss of a water
      molecule from the 8-hydroperoxide has been shown to occur in aqueous solution.
      Subsequent addition of a water molecule at C5 leads to the generation of a
      spiroiminodihy-dantoin compound via a rearrangement that involves an acyl shift.
      However, in both isolated and cellular DNA the latter decomposition pathway is at
      the best a minor process, because only 8-oxo-7,8-dihydroguanine has been found to
      be generated. It is interesting to point out that singlet oxygen has been shown
      to contribute predominantly to the formation of 8-oxo-7,8-dihydroguanine in the
      DNA of bacterial and human cells upon exposure to UVA radiation. It may be added
      that the formation of secondary singlet-oxygen oxidation products of 8-oxo-7,8
      dihydroguanine, including spiroiminodihydantoin and oxaluric acid that were
      characterized in nucleosides and oligonucleotide, respectively, have not yet been
      found in cellular DNA.

PMID- 16808596
TI  - The role of hydration in the distribution of free radical trapping in directly
      ionized DNA.
AB  - The purpose of this study was to elucidate the role of hydration (Gamma) in the
      distribution of free radical trapping in directly ionized DNA. Solid-state films
      of pUC18 (2686 bp) plasmids were hydrated to Gamma in the range 2.5 < or = Gamma
      < or = 22.5 mol water/mol nucleotide. Free radical yields, G(Sigmafr), measured
      by EPR at 4 K are seen to increase from 0.28 +/- 0.01 micromol/J at Gamma = 2.5
      to 0.63 +/- 0.01 micromol/J at Gamma= 22.5, respectively. Based on a semi
      empirical model of the free radical trapping events that follow the initial
      ionizations of the DNA components, we conclude that two-thirds of the holes
      formed on the inner solvation shell (Gamma < 10) transfer to the sugar-phosphate
      backbone. Likewise, of the holes produced by direct ionization of the sugar
      phosphate, about one-third are trapped by deprotonation as neutral sugar
      phosphate radical species, while the remaining two-thirds are found to transfer
      to the bases. This analysis provides the best measure to date for the probability
      of hole transfer (approximately 67%) into the base stack. It can thus be
      predicted that the distribution of holes formed in fully hydrated DNA at 4 K will
      be 78% on the bases and 22% on the sugar-phosphate. Adding the radicals due to
      electron attachment (confined to the pyrimidine bases), the distribution of all
      trapped radicals will be 89% on the bases and 11% on the sugar-phosphate
      backbone. This prediction is supported by partitioning results obtained from the
      high dose-response curves fitted to the two-component model. These results not
      only add to our understanding of how the holes redistribute after ionization but
      are also central to predicting the yield and location of strand breaks in DNA
      exposed to the direct effects of ionizing radiation.

PMID- 16808597
TI  - Radiofrequency electromagnetic fields emitted from base stations of DECT cordless
      phones and the risk of glioma and meningioma (Interphone Study Group, Germany).
AB  - The objective of this study was to test the hypothesis that exposure to
      continuous low-level radiofrequency electromagnetic fields (RF EMFs) increases
      the risk of glioma and meningioma. Participants in a population-based case
      control study in Germany on the risk of brain tumors in relation to cellular
      phone use were 747 incident brain tumor cases between the ages of 30 and 69 years
      and 1494 matched controls. The exposure measure of this analysis was the location
      of a base station of a DECT (Digital Enhanced Cordless Telecommunications)
      cordless phone close to the bed, which was used as a proxy for continuous low
      level exposure to RF EMFs during the night. Estimated odds ratios were 0.82 (95%
      confidence interval: 0.29-2.33) for glioma and 0.83 (0.29-2.36) for meningioma.
      There was also no increasing risk observed with duration of exposure to DECT
      cordless phone base stations. Although the study was limited due to the small
      number of exposed subjects, it is still a first indication that residential low
      level exposure to RF EMFs may not pose a higher risk of brain tumors.

PMID- 16808598
TI  - Comments on "adjusting lung cancer risks for temporal and spatial variations in
      radon concentrations in dwellings in Gansu Province, China" by Lubin et al.
      (Radiat. Res. 163, 571-579, 2005).

PMID- 16808601
TI  - Uses of dosimetry in radiation epidemiology.

PMID- 16808602
TI  - Normal organ radiation dosimetry and associated uncertainties in nuclear
      medicine, with emphasis on iodine-131.
AB  - In many medical applications involving the administration of iodine-131 ((131)I)
      in the form of iodide (I(-)), most of the dose is delivered to the thyroid gland.
      To reliably estimate the thyroid absorbed dose, the following data are required:
      the thyroid gland size (i.e. mass), the fractional uptake of (131)I by the
      thyroid, the spatial distribution of (131)I within the thyroid, and the length of
      time (131)I is retained in the thyroid before it is released back to blood,
      distributed in other organs and tissues, and excreted from the body. Estimation
      of absorbed dose to nonthyroid tissues likewise requires knowledge of the time
      course of activity in each organ. Such data are rarely available, however, and
      therefore dose calculations are generally based on reference models. The MIRD and
      ICRP have published metabolic models and have calculated absorbed doses per unit
      intake for many nuclides and radioactive pharmaceuticals. Given the activity
      taken into the body, one can use such models and make reasonable calculations for
      average organ doses. When normal retention and excretion pathways are altered,
      the baseline models need to be modified, and the resulting organ dose estimates
      are subject to larger errors. This paper describes the historical evolution of
      radioactive isotopes in medical diagnosis and therapy. We nonmathematically
      summarize the methods used in current practice to estimate absorbed dose and
      summarize some of the risk data that have emerged from medical studies of
      patients with special attention to dose and effects observed in those who
      received (131)I-iodide in diagnosis and/or therapy.

PMID- 16808603
TI  - Dose reconstruction for therapeutic and diagnostic radiation exposures: use in
      epidemiological studies.
AB  - This paper describes methods developed specifically for reconstructing individual
      organ- and tissue-absorbed dose of radiation from past exposures from medical
      treatments and procedures for use in epidemiological studies. These methods have
      evolved over the past three decades and have been applied to a variety of medical
      exposures including external-beam radiation therapy and brachytherapy for
      malignant and benign diseases as well as diagnostic examinations. The methods
      used for estimating absorbed dose to organs in and outside the defined treatment
      volume generally require archival data collection, abstraction and review, and
      phantom measurements to simulate past exposure conditions. Three techniques are
      used to estimate doses from radiation therapy: (1) calculation in three
      dimensional mathematical computer models using an extensive database of out-of
      beam doses measured in tissue-equivalent materials, (2) measurement in
      anthropomorphic phantoms constructed of tissue-equivalent material, and (3)
      calculation using a three-dimensional treatment-planning computer. For diagnostic
      exposures, doses are estimated from published data and software based on Monte
      Carlo techniques. We describe and compare these methods of dose estimation and
      discuss uncertainties in estimated organ doses and potential for future
      improvement. Seven epidemiological studies are discussed to illustrate the
      methods.

PMID- 16808604
TI  - The chornobyl accident: estimation of radiation doses received by the Baltic and
      Ukrainian cleanup workers.
AB  - During the first day after the explosion, the Chornobyl accident of April 26,
      1986 exposed a few hundred emergency workers to high dose levels ranging up to 16
      Gy, resulting in acute radiation syndrome. Subsequently, several hundred thousand
      cleanup workers were sent to the Chornobyl power plant to mitigate the
      consequences of the accident. Depending on the nature of the work to be carried
      out, the cleanup workers were sent for periods ranging from several minutes to
      several months. The average dose from external radiation exposure that was
      received by the cleanup workers was about 170 mGy in 1986 and decreased from year
      to year. The radiation exposure was mainly due to external irradiation from gamma
      ray-emitting radionuclides and was relatively homogeneous over all organs and
      tissues of the body. To assess the possible health consequences of external
      irradiation at relatively low dose rates, the U.S. National Cancer Institute is
      involved in two studies of Chornobyl cleanup workers: (1) a study of cancer
      incidence and thyroid disease among Estonian, Latvian and Lithuanian workers, and
      (2) a study of leukemia and other related blood diseases among Ukrainian workers.
      After an overview of the sources of exposure and of the radiation doses received
      by the cleanup workers, a description of the efforts made to estimate individual
      doses in the Baltic and Ukrainian studies is presented.

PMID- 16808605
TI  - External dose estimation for nuclear worker studies.
AB  - Epidemiological studies of nuclear workers are an important source of direct
      information on the health effects of exposure to radiation at low doses and low
      dose rates. These studies have the important advantage of doses that have been
      measured objectively through the use of personal dosimeters. However, to make
      valid comparisons of worker-based estimates with those obtained from data on A
      bomb survivors or persons exposed for medical reasons, attention must be given to
      potential biases and uncertainties in dose estimates. This paper discusses
      sources of error in worker dose estimates and describes efforts that have been
      made to quantify these errors. Of particular importance is the extensive study of
      errors in dosimetry that was conducted as part of a large collaborative study of
      nuclear workers in 15 countries being coordinated by the International Agency for
      Research on Cancer. The study, which focused on workers whose dose was primarily
      from penetrating gamma radiation in the range 100 keV to 3 MeV, included (1)
      obtaining information on dosimetry practices and radiation characteristics
      through the use of questionnaires; (2) two detailed studies of exposure
      conditions, one of nuclear power plants and the other of mixed activity
      facilities; and (3) a study of dosimeter response characteristics that included
      laboratory testing of 10 dosimeter designs commonly used historically. Based on
      these efforts, facility- and calendar year-specific adjustment factors have been
      developed, which will allow risks to be expressed as functions of organ doses
      with reasonable confidence.

PMID- 16808606
TI  - Estimating historical radiation doses to a cohort of U.S. radiologic
      technologists.
AB  - Data have been collected and physical and statistical models have been
      constructed to estimate unknown occupational radiation doses among 90,000 members
      of the U.S. Radiologic Technologists cohort who responded to a baseline
      questionnaire during the mid-1980s. Since the availability of radiation dose data
      differed by calendar period, different models were developed and applied for
      years worked before 1960, 1960- 1976 and 1977-1984. The dose estimation used
      available film-badge measurements (approximately 350,000) for individual cohort
      members, information provided by the technologists on their work history and
      protection practices, and measurement and other data derived from the literature.
      The dosimetry model estimates annual and cumulative occupational badge doses
      (personal dose equivalent) for each technologist for each year worked from 1916
      through 1984 as well as absorbed doses to organs and tissues including bone
      marrow, female breast, thyroid, ovary, testes, lung and skin. Assumptions have
      been made about critical variables including average energy of X rays, use of
      protective aprons, position of film badges, and minimum detectable doses.
      Uncertainty of badge and organ doses was characterized for each year of each
      technologist's working career. Monte Carlo methods were used to generate
      estimates of cumulative organ doses for preliminary cancer risk analyses. The
      models and predictions presented here, while continuing to be modified and
      improved, represent one of the most comprehensive dose reconstructions undertaken
      to date for a large cohort of medical radiation workers.

PMID- 16808607
TI  - A dose threshold for a medium transfer bystander effect for a human skin cell
      line.
AB  - The existence of radiation-induced bystander effects mediated by diffusible
      factors is now accepted, but the mechanisms and precise behavior at low doses
      remain unclear. We exposed cells to gamma-ray doses in the range 0.04 mGy-5 Gy,
      harvested the culture medium, and transferred it to unirradiated reporter cells.
      Calcium fluxes and clonogenic survival were measured in the recipients. We show
      evidence for a dose threshold around 2 mGy for the human skin cell line used with
      a suggestion of increased survival below that dose. Similar experiments using
      direct gamma irradiation showed no reduction in survival until the dose exceeded
      7 mGy. Preliminary data for neutrons where the gamma-ray dose was kept below the
      bystander threshold do not show a significant bystander effect in the dose range
      1-33 mGy. A lack of a bystander response with neutrons occurred at around 1 Gy,
      where significant cell killing from direct irradiation was observed. The result
      may have implications for understanding the role of bystander effects at low
      doses.

PMID- 16808608
TI  - Radon exposure assessment and dosimetry applied to epidemiology and risk
      estimation.
AB  - Epidemiological studies of underground miners provide the primary basis for radon
      risk estimates for indoor exposures as well as mine exposures. A major source of
      uncertainty in these risk estimates is the uncertainty in radon progeny exposure
      estimates for the miners. Often the exposure information is very incomplete, and
      exposure estimation must rely on interpolations, extrapolations and
      reconstruction of mining conditions decades before, which might differ markedly
      from those in more recent times. Many of the measurements that were carried out
      commonly for health protection purposes-are not likely to be representative of
      actual exposures. Early monitoring was often of radon gas rather than of the
      progeny, so that quantifying exposure requires an estimate of the equilibrium
      fraction under the conditions existing at the time of the reported measurement.
      In addition to the uncertainty in radon progeny exposure, doses from gamma
      radiation, inhaled radioactive dust, and thoron progeny have historically been
      neglected. These may induce a systematic bias in risk estimates and add to the
      overall uncertainty in risk estimates derived from the miner studies. Unlike
      other radiogenic cancer risk estimates, numerical risk estimates derived for
      radon from epidemiology are usually expressed as a risk per unit exposure rather
      than as a risk per unit dose to a target tissue. Nevertheless, dosimetric
      considerations are important when trying to compare risks under different
      exposure conditions, e.g. in mines and homes. A recent comparative assessment of
      exposure conditions indicates that, for equal radon progeny exposures, the dose
      in homes is about the same as in mines. Thus, neglecting other possible
      differences, such as the presence in mines of other potential airborne
      carcinogens, the risk per unit progeny exposure should be about the same for
      indoor exposures as observed in miners. Results of case-control studies of lung
      cancer incidence in homes monitored for radon are reasonably consistent with what
      would be projected from miner studies. Measurements of exposure in these indoor
      case-control studies rely on different types of detectors than those used in
      mines, and the estimates of exposure are again a major source of uncertainty in
      these studies.

PMID- 16808609
TI  - Review of methods of dose estimation for epidemiological studies of the
      radiological impact of nevada test site and global fallout.
AB  - Methods to assess radiation doses from nuclear weapons test fallout have been
      used to estimate doses to populations and individuals in a number of studies.
      However, only a few epidemiology studies have relied on fallout dose estimates.
      Though the methods for assessing doses from local and regional compared to global
      fallout are similar, there are significant differences in predicted doses and
      contributing radionuclides depending on the source of the fallout, e.g. whether
      the nuclear debris originated in Nevada at the U.S. nuclear test site or whether
      it originated at other locations worldwide. The sparse historical measurement
      data available are generally sufficient to estimate external exposure doses
      reasonably well. However, reconstruction of doses to body organs from ingestion
      and inhalation of radionuclides is significantly more complex and is almost
      always more uncertain than are external dose estimates. Internal dose estimates
      are generally based on estimates of the ground deposition per unit area of
      specific radionuclides and subsequent transport of radionuclides through the food
      chain. A number of technical challenges to correctly modeling deposition of
      fallout under wet and dry atmospheric conditions still remain, particularly at
      close-in locations where sizes of deposited particles vary significantly over
      modest changes in distance. This paper summarizes the various methods of dose
      estimation from weapons test fallout and the most important dose assessment and
      epidemiology studies that have relied on those methods.

PMID- 16808610
TI  - Dose estimation for atomic bomb survivor studies: its evolution and present
      status.
AB  - In the decade after the bombings of Hiroshima and Nagasaki, several large cohorts
      of survivors were organized for studies of radiation health effects. The U.S.
      Atomic Bomb Casualty Commission (ABCC) and its U.S./Japan successor, the
      Radiation Effects Research Foundation (RERF), have performed continuous studies
      since then, with extensive efforts to collect data on survivor locations and
      shielding and to create systems to estimate individual doses from the bombs'
      neutrons and gamma rays. Several successive systems have been developed by
      extramural working groups and collaboratively implemented by ABCC and RERF
      investigators. We describe the cohorts and the history and evolution of dose
      estimation from early efforts through the newest system, DS02, emphasizing the
      technical development and use of DS02. We describe procedures and data developed
      at RERF to implement successive systems, including revised rosters of survivors,
      development of methods to calculate doses for some classes of persons not fitting
      criteria of the basic systems, and methods to correct for bias arising from
      errors in calculated doses. We summarize calculated doses and illustrate their
      change and elaboration through the various systems for a hypothetical example
      case in each city. We conclude with a description of current efforts and plans
      for further improvements.

PMID- 16808611
TI  - LET-dependent survival of irradiated normal human fibroblasts and their
      descendents.
AB  - Evidence has accumulated showing that ionizing radiations persistently perturb
      genomic stability and induce delayed reproductive death in the progeny of
      survivors; however, the linear energy transfer (LET) dependence of these
      inductions has not been fully characterized. We have investigated the cell
      killing effectiveness of gamma rays (0.2 keV/microm) and six different beams of
      heavy-ion particles with LETs ranging from 16.2 to 1610 keV/microm in normal
      human fibroblasts. First, irradiated confluent density-inhibited cultures were
      plated for primary colony formation, revealing that the relative biological
      effectiveness (RBE) based on the primary 10% survival dose peaked at 108
      keV/microm and that the inactivation cross section increased proportionally up to
      437 keV/microm. Second, cells harvested from primary colonies were plated for
      secondary colony formation, showing that delayed reproductive death occurred in a
      dose-dependent fashion. While the RBE based on the secondary 80% survival dose
      peaked at 108 keV/microm, very little difference in LET was observed in the RBE
      based on secondary survival at the primary 10% survival dose. Our present results
      indicate that delayed reproductive death arising only during secondary colony
      formation is independent of LET and is more likely to be dependent on initial
      damages having been fixed during primary colony formation.

PMID- 16808612
TI  - Development of an improved dose reconstruction system for the Techa River
      population affected by the operation of the Mayak Production Association.
AB  - The Techa River Dosimetry System (TRDS) has been developed to provide estimates
      of dose received by approximately 30,000 members of the Extended Techa River
      Cohort (ETRC). Members of the ETRC were exposed beginning in 1949 to significant
      levels of external and internal (mainly from (90)Sr) dose but at low to moderate
      dose rates. Members of this cohort are being studied in an effort to test the
      hypothesis that exposure at low to moderate dose rates has the same ability to
      produce stochastic health effects as exposure at high dose rates. The current
      version of the TRDS is known as TRDS-2000 and is the subject of this paper. The
      estimated doses from (90)Sr are supported strongly by approximately 30,000
      measurements made with a tooth beta-particle counter, measurements of bones
      collected at autopsy, and approximately 38,000 measurements made with a special
      whole-body counter that detects the bremsstrahlung from (90)Y. The median doses
      to the red bone marrow and the bone surface are 0.21 and 0.37 Gy, respectively.
      The maximum doses to the red bone marrow and bone surface are 2.0 and 5.2 Gy,
      respectively. Distributions of dose to other organs are provided and are lower
      than the values given above. Directions for future work are discussed.

PMID- 16808613
TI  - Questionnaire- and measurement-based individual thyroid doses in Ukraine
      resulting from the Chornobyl nuclear reactor accident.
AB  - The U.S. National Cancer Institute (NCI), in cooperation with the Ministries of
      Health of Belarus and of Ukraine, is involved in epidemiological studies of
      thyroid diseases presumably related to the Chornobyl accident, which occurred in
      Ukraine on 26 April 1986. Within the framework of these studies, individual
      thyroid absorbed doses, as well as uncertainties, have been estimated for all
      members of the cohorts (13,215 Ukrainians and 11,918 Belarusians), who were
      selected from the large group of children aged 0 to 18 whose thyroids were
      monitored for gamma radiation within a few weeks after the accident. Information
      on the residence history and dietary habits of each cohort member was obtained
      during personal interviews. The methodology used to estimate the thyroid absorbed
      doses resulting from intakes of (131)I by the Ukrainian cohort subjects is
      described. The model of thyroid dose estimation is run in two modes:
      deterministic and stochastic. In the stochastic mode, the model is run 1,000
      times for each subject using a Monte Carlo procedure. The geometric means of the
      individual thyroid absorbed doses obtained in the stochastic mode range from
      0.0006 to 42 Gy. The arithmetic and geometric means of these individual thyroid
      absorbed doses over the entire cohort are 0.68 and 0.23 Gy, respectively. On
      average, the individual thyroid dose estimates obtained in the deterministic mode
      are about the same as the geometric mean doses obtained in the stochastic mode,
      while the arithmetic mean thyroid absorbed doses obtained in the stochastic mode
      are about 20% higher than those obtained in the deterministic mode. The
      distributions of the 1000 values of the individual thyroid absorbed dose
      estimates are found to be approximately lognormal, with geometric standard
      deviations ranging from 1.6 to 5.0 for most cohort subjects. For the time being,
      only the thyroid doses resulting from intakes of (131)I have been estimated for
      all subjects. Future work will include the estimation of the contributions to the
      thyroid doses resulting from external irradiation and from intakes of short-lived
      ((133)I and (132)Te) and long-lived ((134)Cs and (137)Cs) radionuclides, as well
      as efforts to reduce the uncertainties.

PMID- 16808614
TI  - Retrospective assessment of radiation exposure using biological dosimetry:
      chromosome painting, electron paramagnetic resonance and the glycophorin a
      mutation assay.
AB  - Biological monitoring of dose can contribute important, independent estimates of
      cumulative radiation exposure in epidemiological studies, especially in studies
      in which the physical dosimetry is lacking. Three biodosimeters that have been
      used in epidemiological studies to estimate past radiation exposure from external
      sources will be highlighted: chromosome painting or FISH (fluorescence in situ
      hybridization), the glycophorin A somatic mutation assay (GPA), and electron
      paramagnetic resonance (EPR) with teeth. All three biodosimeters have been
      applied to A-bomb survivors, Chernobyl clean-up workers, and radiation workers.
      Each biodosimeter has unique advantages and limitations depending upon the level
      and type of radiation exposure. Chromosome painting has been the most widely
      applied biodosimeter in epidemiological studies of past radiation exposure, and
      results of these studies provide evidence that dose-related translocations
      persist for decades. EPR tooth dosimetry has been used to validate dose models of
      acute and chronic radiation exposure, although the present requirement of
      extracted teeth has been a disadvantage. GPA has been correlated with physically
      based radiation dose after high-dose, acute exposures but not after low-dose,
      chronic exposures. Interindividual variability appears to be a limitation for
      both chromosome painting and GPA. Both of these techniques can be used to
      estimate the level of past radiation exposure to a population, whereas EPR can
      provide individual dose estimates of past exposure. This paper will review each
      of these three biodosimeters and compare their application in selected
      epidemiological studies.

PMID- 16808615
TI  - Some statistical implications of dose uncertainty in radiation dose-response
      analyses.
AB  - Statistical dose-response analyses in radiation epidemiology can produce
      misleading results if they fail to account for radiation dose uncertainties.
      While dosimetries may differ substantially depending on the ways in which the
      subjects were exposed, the statistical problems typically involve a predominantly
      linear dose-response curve, multiple sources of uncertainty, and uncertainty
      magnitudes that are best characterized as proportional rather than additive. We
      discuss some basic statistical issues in this setting, including the bias and
      shape distortion induced by classical and Berkson uncertainties, the effect of
      uncertain dose-prediction model parameters on estimated dose-response curves, and
      some notes on statistical methods for dose-response estimation in the presence of
      radiation dose uncertainties.

PMID- 16808616
TI  - Histone H2AX phosphorylation in normal human cells irradiated with focused
      ultrasoft X rays: evidence for chromatin movement during repair.
AB  - DNA repair within the cell nucleus is a dynamic process involving a close
      interaction between repair proteins and chromatin structure. Recent studies have
      indicated a quantitative relationship between DNA double-strand break induction
      and histone H2AX phosphorylation. The dynamics of this process within individual
      cell nuclei is unknown. To address this, we have used a novel focused ultrasoft X
      ray microprobe that is capable of inducing localized DNA damage within a
      subnuclear area of intact cells with a 2.5-microm-diameter beam spot. The present
      investigation was undertaken to explore the influence of focused irradiation of
      individual nuclei with 1.49 keV characteristic aluminum K-shell (AlK) X rays on
      H2AX phosphorylation in normal human cells. Immunofluorescence analyses revealed
      that significant diffusion of the initial spots of clustered foci of
      phosphorylated H2AX occurred in a time-dependent fashion after exposure to AlK X
      rays. Irradiation under cooled conditions resulted in a reduction in the size of
      spots of clustered foci of phosphorylated H2AX as well as of individual
      phosphorylated H2AX foci. These findings strongly suggest that diffusion of the
      chromatin microenvironment occurs during the repair of DNA damage. We also found
      that AlK ultrasoft X rays (71 foci per gray) were 2.2-fold more effective at the
      initial formation of phosphorylated H2AX foci than with conventional X rays (32
      foci per gray), and that the time required to eliminate 50% of the initial number
      of foci was 3.4-fold longer in AlK-irradiated cells than that in cells exposed to
      conventional X rays. For conventional X rays, we also report significant
      accumulation of larger-sized foci at longer times after irradiation.

PMID- 16808617
TI  - Dosimetry for epidemiological studies: learning from the past, looking to the
      future.

PMID- 16808618
TI  - Atm haploinsufficiency does not affect ionizing radiation mutagenesis in solid
      mouse tissues.
AB  - Ataxia telangiectasia (AT) is a hereditary disease with autosomal recessive
      inheritance of ATM (ataxia telangiectasia mutation) alleles. AT is associated
      with severe sensitivity to ionizing radiation and a strong predisposition to
      develop cancer. A modest increase in cancer, particularly for the breast, has
      been shown for ATM carriers (i.e. heterozygotes), and a modest increase in
      radiation sensitivity has also been shown for those patients and their cells.
      However, the extent of these effects is unclear. Based on the well-established
      relationship between cancer and mutation, we used a mouse model for Atm
      haploinsufficiency to ask whether partial loss of Atm function could lead to an
      increased mutagenic response for solid tissues of mice exposed to radiation. The
      autosomal mouse Aprt gene was used as the mutational target and kidney and ear as
      the target tissues in B6D2F1 hybrids. Although induction of autosomal mutations
      was readily demonstrated in both tissues, a comparison of these data with those
      from an identical study performed with B6D2F1 mice that were wild-type for Atm
      (Cancer Res. 62, 1518-1523, 2002) revealed that Atm haploinsufficiency did not
      alter the radiation mutagenic response for the cells of either tissue. Moreover,
      no effect of Atm haploinsufficiency on reduced cellular viability due to
      radiation exposure was observed. The results demonstrate that Atm
      haploinsufficiency does not alter the radiation mutagenic response or decrease
      viability for normally quiescent cells in solid tissues of the mouse.

PMID- 16808619
TI  - gamma-H2AX foci after low-dose-rate irradiation reveal atm haploinsufficiency in
      mice.
AB  - We have investigated the use of the gamma-H2AX assay, reflecting the presence of
      DNA double-strand breaks (DSBs), as a possible means for identifying individuals
      who may be intermediate with respect to the extremes of hyper-radiosensitivity
      phenotypes. In this case, cells were studied from mice that were normal (Atm+/+),
      heterozygous (Atm+/-), or homozygous recessive (Atm-/-) for a truncating mutation
      in the Atm gene. After single acute (high-dose-rate) exposures, differences in
      mean numbers of gamma-H2AX foci per cell between samples from Atm+/+ and Atm-/-
      mice were clear at nearly all sampling times, but at no sampling time was there a
      clear distinction for cells from Atm+/+ and Atm+/- mice. In contrast, under
      conditions of low-dose-rate irradiation at 10 cGy/h, appreciable differences in
      the levels of gamma-H2AX foci per cell were observed in synchronized G1 cells
      derived from Atm+/- mice relative to cells from Atm+/+ mice. The levels were
      intermediate between those for cells from Atm+/+ and Atm-/- mice. After 24 h
      exposure at this dose rate, measurements in cells from four different mice for
      each genotype yielded mean frequencies of foci per cell of 1.77 +/- 0.13 (SEM)
      for Atm+/+ cells, 4.75 +/- 0.20 for the Atm+/- cells, and 11.10 +/- 0.33 for the
      Atm-/-cells. The distributions of foci per G1 cell were not significantly
      different from Poisson. To the extent that variations in sensitivity with respect
      to gamma-H2AX focus formation reflect variations in radiosensitivity for
      biological effects of concern, such as carcinogenesis, and that similar
      differences are seen for other genetic DNA DSB processing defects in general,
      this assay may provide a relatively straightforward means for distinguishing
      individuals who may be mildly hypersensitive to radiation such as we observed for
      Atm heterozygous mice.

PMID- 16808620
TI  - The delayed manifestation of T-cell receptor (TCR) variants in X-irradiated mice
      depends on Trp53 status.
AB  - The influence of Trp53 on the radiation-induced elevation of T-cell receptor
      (TCR) variant fractions was examined in splenic T lymphocytes of Trp53-proficient
      and -deficient mice. Wild-type Trp53+/+, heterozygous Trp53+/- and null Trp53-/-
      mice were exposed to 3 Gy of X rays at 8 weeks of age. The fraction of TCR
      defective variants was measured at various times after irradiation. Initially,
      the TCR variant fraction increased rapidly and reached its maximum level at 9
      days after irradiation before decreasing gradually. In Trp53+/+ and Trp53+/-
      mice, the TCR variant fraction fell to normal background levels at 16 and 20
      weeks of age, respectively. In contrast, the TCR variant fraction of Trp53-/-
      mice failed to decrease to background levels during the observation period.
      Baseline levels were then maintained for approximately 60 weeks in the Trp53+/+
      mice and approximately 40 weeks in the Trp53+/- mice. After the long flat period,
      a significant re-increase in the fraction of TCR variants was found after 72
      weeks of age in the irradiated Trp53+/+ mice and after 44 weeks of age in the
      irradiated Trp53+/- mice. Measurement of the fraction of apoptotic cells in the
      spleen and thymus 4 h after X irradiation at these ages in Trp53+/+ and Trp53+/-
      mice demonstrated a reduction in apoptosis in the irradiated mice compared to the
      nonirradiated mice. This suggests that the delayed increase in TCR variants after
      irradiation is due to a reduction in Trp53-dependent apoptosis.

PMID- 16808621
TI  - Array-CGH analyses of murine malignant lymphomas: genomic clues to understanding
      the effects of chronic exposure to low-dose-rate gamma rays on lymphomagenesis.
AB  - We previously reported that mice chronically irradiated with low-dose-rate gamma
      rays had significantly shorter mean life spans than nonirradiated controls. This
      life shortening appeared to be due primarily to earlier death due to malignant
      lymphomas in the irradiated groups (Tanaka et al., Radiat. Res. 160, 376-379,
      2003). To elucidate the molecular pathogenesis of murine lymphomas after low-dose
      rate irradiation, chromosomal aberrations in 82 malignant lymphomas from mice
      irradiated at a dose rate of 21 mGy/day and from nonirradiated mice were compared
      precisely by microarray-based comparative genomic hybridization (array-CGH)
      analysis. The array carried 667 BAC clones densely selected for the genomic
      regions not only of lymphoma-related loci but also of surface antigen receptors,
      enabling immunogenotyping. Frequent detection of the apparent loss of the Igh
      region on chromosome 12 suggested that most lymphomas in both groups were of B
      cell origin. Array-CGH profiles showed a frequent gain of whole chromosome 15 in
      lymphomas predominantly from the irradiated group. The profiles also demonstrated
      copy-number imbalances of partial chromosomal regions. Partial gains on
      chromosomes 12, 14 and X were found in tumors from nonirradiated mice, whereas
      losses on chromosomes 4 and 14 were significantly associated with the irradiated
      group. These findings suggest that lymphomagenesis under the effects of
      continuous low-dose-rate irradiation is accelerated by a mechanism different from
      spontaneous lymphomagenesis that is characterized by the unique spectrum of
      chromosomal aberrations.

PMID- 16808622
TI  - Prostate cancer treatment is enhanced by genistein in vitro and in vivo in a
      syngeneic orthotopic tumor model.
AB  - Pretreatment with genistein, a bioactive component of soy isoflavones,
      potentiated cell killing induced by radiation in human PC-3 prostate cancer cells
      in vitro. Using an orthotopic xenograft in nude mice, we demonstrated that
      genistein combined with prostate tumor irradiation caused greater inhibition of
      primary tumor growth and increased control of spontaneous metastasis to para
      aortic lymph nodes, increasing mouse survival. Paradoxically, treatment with
      genistein alone increased metastasis to lymph nodes. This observation is of
      concern in relation to soy-based clinical trials for cancer patients. To address
      whether this observation is because nude mice have an impaired immune system,
      these studies were repeated in orthotopic RM-9 prostate tumors in syngeneic
      C57BL/6 mice. The combination of genistein with radiation in this model also
      caused a greater inhibition of primary tumor growth and spontaneous metastasis to
      regional para-aortic lymph nodes, whereas treatment with genistein alone showed a
      trend to increased lymph node metastasis. Data from the syngeneic and xenograft
      models are comparable and indicate that the combination of genistein with
      radiotherapy is more effective and safer for prostate cancer treatment than
      genistein alone, which promotes metastatic spread to regional lymph nodes.

PMID- 16808623
TI  - Design of a rotating facility for extracorporal treatment of an explanted liver
      with disseminated metastases by boron neutron capture therapy with an epithermal
      neutron beam.
AB  - In 2001, at the TRIGA reactor of the University of Pavia (Italy), a patient
      suffering from diffuse liver metastases from an adenocarcinoma of the sigmoid was
      successfully treated by boron neutron capture therapy (BNCT). The procedure
      involved boron infusion prior to hepatectomy, irradiation of the explanted liver
      at the thermal column of the reactor, and subsequent reimplantation. A complete
      response was observed. This encouraging outcome stimulated the Essen/Petten BNCT
      group to investigate whether such an extracorporal irradiation could be performed
      at the BNCT irradiation facility at the HFR Petten (The Netherlands), which has
      very different irradiation characteristics than the Pavia facility. A
      computational study has been carried out. A rotating PMMA container with a liver,
      surrounded by PMMA and graphite, is simulated using the Monte Carlo code MCNP.
      Due to the rotation and neutron moderation of the PMMA container, the initial
      epithermal neutron beam provides a nearly homogeneous thermal neutron field in
      the liver. The main conditions for treatment as reported from the Pavia
      experiment, i.e. a thermal neutron fluence of 4 x 10(12) +/- 20% cm(-2), can be
      closely met at the HFR in an acceptable time, which, depending on the defined
      conditions, is between 140 and 180 min.

PMID- 16808624
TI  - Effect of occupational radiation exposures on chromosome aberration rates in
      former plutonium workers.
AB  - A fluorescence in situ hybridization (FISH) method was used to measure chromosome
      aberration rates in lymphocytes of 30 retired plutonium workers with combined
      internal and external radiation doses greater than 0.5 Sv along with 17
      additional workers with predominantly external doses below 0.1 Sv. The former
      group was defined as high-dose and the latter as low-dose with respect to
      occupational radiation exposure. The two groups were compared to each other and
      also to 21 control subjects having no history of occupational radiation exposure.
      Radiation exposures to the high-dose group were primarily the result of internal
      depositions of plutonium and its radioactive decay products resulting from
      various work-related activities and accidents. The median external dose for the
      high-dose group was 280 mSv (range 10-730) compared to a median of 22 mSv (range
      10-76) for the low-dose group. The median internal dose to the bone marrow for
      the high-dose group was 168 mSv (range 29-20,904) while that of the low-dose
      group was considered negligible. Over 200,000 metaphase cells were analyzed for
      chromosome aberrations by painting pairs 1, 4 and 12 in combination with a
      pancentromeric probe. Additionally, 136,000 binucleated lymphocytes were analyzed
      for micronuclei in parallel cultures to assess mitotic abnormalities arising from
      damaged chromosomes. The results showed that the frequency of structural
      aberrations affecting any of the painted chromosomes in the high-dose group
      correlated with the bone marrow dose but not with the external dose. In contrast,
      the frequency of micronuclei did not vary significantly between the study groups.
      The total translocation frequency per genome equivalent x 10(-3) +/- SE was 4.0
      +/- 0.6, 9.0 +/- 1.1 and 17.0 +/- 2.1 for the control, low-dose and high-dose
      groups, respectively. Statistical analysis of the data showed that the frequency
      of total translocations and S-cells correlated with the bone marrow dose, with P
      values of 0.005 and 0.004, respectively. In contrast, these two end points did
      not correlate with the external dose, with P values of 0.45 and 0.39,
      respectively. In conclusion, elevated rates of stable chromosome aberrations were
      found in lymphocytes of former workers decades after plutonium intakes, providing
      evidence that chronic irradiation of hematopoietic precursor cells in the bone
      marrow induces cytogenetically altered cells that persist in peripheral blood.

PMID- 16808625
TI  - Protection of DNA against direct radiation damage by complex formation with
      positively charged polypeptides.
AB  - Radioprotection of DNA from direct-type radiation damage by histones has been
      studied in model systems using complexes of positively charged polypeptides
      (PCPs) with DNA. PCPs bind to DNA via ionic interactions mimicking the mode of
      DNA-histone binding. Direct radiation damage to DNA in films of DNA-PCP complexes
      was quantified as unaltered base release, which correlates closely with DNA
      strand breaks. All types of PCPs tested protected DNA from radiation, with the
      maximum radioprotection being approximately 2.5-fold compared with non-complexed
      DNA. Conformational changes of the DNA induced by PCPs or repair of free radical
      damage on the DNA sugar moiety by PCPs are considered the most feasible
      mechanisms of radioprotection of DNA. The degree of radioprotection of DNA by
      polylysine (PL) increased dramatically on going from pure DNA to a molar ratio of
      PL monomer:DNA nucleotide approximately 1:2, while a further increase in the
      PL:DNA ratio did not offer more radioprotection. This concentration dependence is
      in agreement with the model of PCP binding to DNA that assumes preferential
      binding of positively charged side groups to DNA phosphates in the minor groove,
      so that the maximum occupancy of all minor-groove PCP binding sites is at a molar
      ratio of PCP:DNA = 1:2.

PMID- 16808626
TI  - Mortality among radiation workers at Rocketdyne (Atomics International), 1948
      1999.
AB  - A retrospective cohort mortality study was conducted of workers engaged in
      nuclear technology development and employed for at least 6 months at Rocketdyne
      (Atomics International) facilities in California, 1948-1999. Lifetime
      occupational doses were derived from company records and linkages with national
      dosimetry data sets. International Commission on Radiation Protection (ICRP)
      biokinetic models were used to estimate radiation doses to 16 organs or tissues
      after the intake of radionuclides. Standardized mortality ratios (SMRs) compared
      the observed numbers of deaths with those expected in the general population of
      California. Cox proportional hazards models were used to evaluate dose-response
      trends over categories of cumulative radiation dose, combining external and
      internal organ-specific doses. There were 5,801 radiation workers, including
      2,232 monitored for radionuclide intakes. The mean dose from external radiation
      was 13.5 mSv (maximum 1 Sv); the mean lung dose from external and internal
      radiation combined was 19.0 mSv (maximum 3.6 Sv). Vital status was determined for
      97.6% of the workers of whom 25.3% (n = 1,468) had died. The average period of
      observation was 27.9 years. All cancers taken together (SMR 0.93; 95% CI 0.84
      1.02) and all leukemia excluding chronic lymphocytic leukemia (CLL) (SMR 1.21;
      95% CI 0.69-1.97) were not significantly elevated. No SMR was significantly
      increased for any cancer or for any other cause of death. The Cox regression
      analyses revealed no significant dose-response trends for any cancer. For all
      cancers excluding leukemia, the RR at 100 mSv was estimated as 1.00 (95% CI 0.81
      1.24), and for all leukemia excluding CLL it was 1.34 (95% CI 0.73-2.45). The
      nonsignificant increase in leukemia (excluding CLL) was in accord with
      expectation from other radiation studies, but a similar nonsignificant increase
      in CLL (a malignancy not found to be associated with radiation) tempers a causal
      interpretation. Radiation exposure has not caused a detectable increase in cancer
      deaths in this population, but results are limited by small numbers and
      relatively low career doses.

PMID- 16808627
TI  - Direct detection of 8-oxo-deoxyguanosine using UV resonance Raman spectroscopy.
AB  - 8-oxo-deoxyguanosine (8-oxo-dG) is a major oxidative lesion in DNA and is
      responsible for mutation and cancer. Current techniques for detecting 8-oxo-dG
      are indirect methods. Thus, development of new methodologies is needed to
      directly detect such oxidative lesions. In this article, we have used ultraviolet
      resonance Raman (UVRR) spectroscopy as a novel analytical technique for the
      detection of 8-oxo-dG. Here, the UVRR spectrum of 8-oxo-dG was acquired and
      compared to that of deoxyguanosine (dG) and deoxyadenosine (dA). Data analysis
      shows a distinct UVRR spectrum of 8-oxo-dG with characteristic peaks. Detection
      of 8-oxo-dG was easily achieved from a mixture with dG. These results reveal that
      UVRR spectroscopy shows promise as a direct method for detecting 8-oxo-dG.

PMID- 16808628
TI  - Why is a postmortem examination important when an infant or child dies suddenly?

PMID- 16808629
TI  - Urothelial mucosal malformation: a rare cause for ureteropelvic junction
      obstruction.
AB  - Ureteropelvic junction obstruction (UPJO) constitutes a significant cause of
      morbidity in children and exists in a wide range of severity and clinical
      manifestations. The cause of UPJO remains largely unknown except for a small
      group, in which crossing vessels have been considered etiological. Herein we
      describe a unique case in which intraluminal occlusion was the result of mucosal
      malformation, characterized by invaginated and branching urothelial epithelium
      present in the lamina propria. We believe that the present case is the first such
      description of this type of alteration.

PMID- 16808630
TI  - Periventricular leukomalacia: overview and recent findings.
AB  - Periventricular leukomalacia (PVL), the main substrate for cerebral palsy, is
      characterized by diffuse injury of deep cerebral white matter, accompanied in its
      most severe form by focal necrosis. The classic neuropathology of PVL has given
      rise to several hypotheses about the pathogenesis, largely relating to hypoxia
      ischemia and reperfusion in the sick premature infant. These include free radical
      injury, cytokine toxicity (especially given the epidemiologic association of PVL
      with maternofetal infection), and excitotoxicity. Among the recent findings
      directly in human postmortem tissue is that immunocytochemical markers of lipid
      peroxidation (hydroxy-nonenal and malondialdehyde) and protein nitration
      (nitrotyrosine) are significantly increased in PVL. Premyelinating
      oligodendrocytes, which predominate in periventricular regions during the window
      of vulnerability to PVL (24 to 34 postconceptional weeks), are the targets of
      this free radical injury, and suffer cell death. Susceptibility can be
      attributed, at least in part, to a relative deficiency of superoxide dismutases
      in the preterm white matter, including premyelinating oligodendrocytes. Several
      cytokines, including interferon-gamma (known to be directly toxic to immature
      oligodendroglia in vitro), as well as tumor necrosis factor-alpha and
      interleukins 2 and 6, have been demonstrated in PVL. Microglia, which express
      toll-like receptors to bacterial products such as lipopolysaccharide, are
      increased in PVL white matter and may contribute to the injury. Preliminary work
      suggests a role for glutamate receptors and glutamate transporters in PVL, as has
      been seen in experimental animals. These findings pave the way for eventual
      therapeutic or preventive strategies for PVL.

PMID- 16808631
TI  - Neonatal hepatitis in 2 siblings with Seckel syndrome.
AB  - Seckel syndrome was described as the prototype of the primordial bird-head type
      of dwarfism. We report 2 cases of Seckel syndrome in siblings. Both cases showed
      peculiar phenotypic features. Autopsy was performed and microscopic examination
      of the livers displayed histologic features of neonatal hepatitis. In addition,
      our younger patient had central nervous system anomalies such as agenesis of
      corpus callosum, cerebral cyst, and primitive convolutional pattern. No previous
      reports of liver disease exist in patients with Seckel syndrome. The pathologic
      findings of such an unusual association and a review of literature are presented.

PMID- 16808632
TI  - Portopulmonary hypertension in childhood presenting as sudden death.
AB  - We present the case of a 9-year-old boy with portal hypertension who died
      suddenly and unexpectedly due to pulmonary hypertensive crisis during a routine
      endoscopic procedure. He had known portal hypertension with esophageal varices
      but had no preceding clinical symptoms suggestive of significant pulmonary
      hypertensive disease despite postmortem histological evidence of advanced
      pulmonary vascular changes. Portopulmonary hypertension is a well-described and
      distinct clinical syndrome that is rare in childhood and is associated with a
      relatively poor prognosis. Occasional patients with histologically advanced
      disease may remain asymptomatic but present with pulmonary hypertensive crisis.
      Children with portopulmonary hypertension should be considered at high risk for
      surgical procedures, and pulmonary hypertensive complications should be excluded
      as a cause of death in all children dying suddenly in the setting of portal
      hypertension.

PMID- 16808633
TI  - Umbilical cord stricture and overcoiling are common causes of fetal demise.
AB  - Although umbilical cord stricture and umbilical cord overcoiling have been
      established as causes of intrauterine fetal demise, relatively few studies
      addressed this issue, most of them being case reports. We reviewed a total of 268
      fetal autopsies during a 3-year period from 1998 to 2001. One hundred thirty nine
      cases of fetal demise including spontaneous abortion were identified. Nineteen
      percent (26 of 139) were associated with umbilical cord stricture, overcoiling,
      or a combination of both. Stricture of the umbilical cord was defined as a
      decrease in diameter in relation of the remaining umbilical cord; overcoiling as
      0.3 coil/cm or greater. Fetal demise most commonly occurred in the second
      trimester, with a mean gestation age of 21 weeks. The average maternal age was 33
      years; 15% had a prior fetal demise. We found that 77% (20 of 26) of these cases
      had umbilical cord stricture only or with overcoiling, 23% (6 of 26) had
      umbilical cord overcoiling alone. Localized deficiency of Wharton's jelly and
      increased collagen were found in all cases with umbilical cord stricture with or
      without overcoiling. In patients with umbilical cord overcoiling alone, 25% had
      Wharton's jelly deficiency; half of them had increased collagen deposition in the
      umbilical cords. The placenta was reviewed for secondary thrombosis of the
      vessels of the chorionic plate. Thrombosis of the vessels of the chorionic plate
      was noted in 54% of the patients. Our study suggests that umbilical cord
      stricture and cord overcoiling may represent two distinct pathological entities
      commonly causing fetal demise. This observation reinforces the importance of a
      fetal autopsy with careful examination of the placenta and umbilical cord with
      documentation of the cord coil index.

PMID- 16808634
TI  - Nonobstructive neonatal cholestasis: clinical outcome and scoring of the
      histopathological changes in liver biopsies.
AB  - The clinical outcome of nonobstructive neonatal cholestasis (NC) cases varies
      greatly and the prognosis is generally unpredictable. In this study, we aimed to
      evaluate the prognostic benefits of qualitative analysis of histopathological
      changes in nonobstructive NC cases. A total of 28 nonobstructive NC cases (18
      neonatal hepatitis; 10 intrahepatic bile duct paucity) were studied. We analyzed
      the relationship between histopathological and clinical parameters. Hepatic
      inflammation, bridging necrosis, pericellular fibrosis, giant cell
      transformation, and extramedullary hematopoiesis were evaluated and scored
      according to their absence or presence in each case. The sum of the
      histopathological scores was accepted as "total pathological injury score." The
      height percentiles, the presence and the degree of hepatomegaly and ascites, and
      serum alanine aminotransferase (ALT), albumin, and bilirubin levels and
      prothrombin time were also evaluated and scored. The patients were divided into 2
      clinical course groups considered "good" or "bad" according to the total clinical
      scores. For statistical analysis, Pearson's chi-square test, Mann-Whitney U-test,
      and receiver operating characteristic curve were used. We found a statistically
      significant negative relation between the clinical course and total pathological
      injury score (P = 0.042) and pericellular fibrosis (P = 0.016). In conclusion,
      during the interpretation of liver biopsies of nonobstructive NC, scoring of
      histopathological changes should be done for assessing the clinical prognostic
      outcome.

PMID- 16808635
TI  - Screening for RB1 mutations in tumor tissue using denaturing high performance
      liquid chromatography, multiplex ligation-dependent probe amplification, and loss
      of heterozygosity analysis.
AB  - Retinoblastoma is a malignant retinal neoplasm arising in infancy as a result of
      inactivating mutations in both alleles of the retinoblastoma susceptibility gene,
      RB1. Identification of the causative RB1 mutations in a patient assists in the
      clinical management of the affected patient and risk assessment of family
      members, principally on the basis of whether there is a germline mutation. In
      this paper, we describe our experience with molecular analysis of RB1 mutations
      in tumor and nontumor samples from 18 retinoblastoma patients, using multiplex
      ligation dependent probe amplification (MLPA) to detect large deletions or
      duplications, microsatellite analysis to detect loss of heterozygosity (LOH), and
      denaturing high performance liquid chromatography (D-HPLC) analysis to detect
      point mutations and small insertions or deletions. We found LOH in 71% of all
      cases, and 83% of these were due to acquired isodisomy rather than chromosomal
      deletions. Small mutations identified by D-HPLC accounted for 78% of the non-LOH
      mutations, and large deletions/duplications detected by MLPA accounted for the
      remaining 22%. We give the first report of a large, multiexon duplication in RB1
      of exons 8 to 18.

PMID- 16808636
TI  - IUGR and laminar necrosis of the placental membranes.

PMID- 16808637
TI  - An association of pleuropulmonary blastoma and cystic nephroma: possible genetic
      association.
AB  - The association of pleuropulmonary blastoma and cystic nephroma is an uncommon
      entity, with only 4 cases of such an association in the same patient described in
      English literature. We report a 5th histologically documented case in a 32-month
      old boy. The boy underwent a pulmonary biopsy that showed a pleuropulmonary
      blastoma and a nephrectomy that showed a cystic nephroma. The pleuropulmonary
      mass showed an important regression with postbiopsy chemotherapy, allowing
      subsequent tumorectomy. To date very little is known about this rare entity, and
      a genetic link between these 2 tumors is hypothesized.

PMID- 16808638
TI  - Giant inflammatory polyposis coli as a manifestation of Crohn's disease in
      patients with coexistent cystic fibrosis.
AB  - Crohn's disease (CD) arising in children with cystic fibrosis (CF) is well
      recognized. Indeed, reports suggest that CD is significantly more common in
      patients with CF than in the general population. Giant inflammatory polyposis is
      a rare manifestation of idiopathic inflammatory bowel disease and may complicate
      both ulcerative colitis and CD. Giant inflammatory polyposis has not been
      specifically reported in patients with coexistent CF and CD. Herein, we report
      the occurrence of giant inflammatory polyposis in 2 boys attending a tertiary
      care hospital, with an established diagnosis of CF who subsequently developed CD.
      Both boys required surgical treatment for CD. In addition to classical features
      of CD, both colonic resection specimens showed giant inflammatory polyposis. The
      appearances were modified by the presence of a layer of thick mucus. It is
      suggested that the coexistence of CF in patients with CD may predispose to the
      development of giant inflammatory polyposis. In addition to contributing to their
      development, it also appears that there is a propensity for CF to alter the
      morphological appearance of giant inflammatory polyposis. This may lead to
      diagnostic confusion when examining endoscopic biopsies.

PMID- 16808639
TI  - Twin-to-twin transfusion syndrome, vein of galen malformation, and transposition
      of the great arteries in a pair of monochorionic twins: coincidence or related
      association?
AB  - The pathogenetic mechanisms leading to the development of congenital heart
      disease and congenital intracranial arteriovenous malformation are still unclear.
      We report on a monochorionic twin pregnancy with twin-to-twin transfusion
      syndrome (TTTS), in which vein of Galen malformation (VGM) was diagnosed in the
      donor twin and transposition of the great arteries (TGA) in the recipient twin.
      The development of TTTS, VGM, and TGA in a single monochorionic pregnancy could
      be pure coincidence, but there might also be a causative link. We discuss the
      possible contribution of genetic factors, fetal flow fluctuations, vascular
      endothelial growth factors, and the process of twinning itself to the development
      of these congenital anomalies.

PMID- 16808640
TI  - Brain malformations associated with cell migration.

PMID- 16808641
TI  - Polar spongioblastoma of the spinal cord: a case report.
AB  - "Rhythmic palisading" is a striking histologic pattern infrequently encountered
      in a variety of central nervous system (CNS) tumors. We present the case of an
      infant with a large spinal cord lesion wherein all sampled tissue showed columnar
      arrangements of palisaded cells, typical of polar spongioblastoma. The tumor was
      briskly proliferative, focally necrotic, and variably expressed S100, glial
      fibrillary acidic protein, neuron specific enolase, and p53 by
      immunohistochemistry. Fluorescence in situ hybridization failed to reveal
      isochromosome 17q, EGFR amplification, or deletions of 1p, 19q, 22q11.2, 10q, or
      p16. Despite chemotherapy and decadron, he developed lesional necrosis and
      intracranial metastases and died less than 1 mo from presentation. This case
      illustrates polar spongioblastoma as a distinctive histologic pattern that can
      occur in embryonal CNS tumors. Discrimination of these rare aggressive lesions
      from other CNS tumors with focal palisaded architecture is crucial as the
      treatment and prognosis of the latter may differ significantly.

PMID- 16808642
TI  - Multiple endocrine neoplasia type 2B diagnosed on suction rectal biopsy in
      infancy: a report of 2 cases.
AB  - Suction rectal biopsies in a newborn and a 10-month-old infant presenting with
      intestinal obstruction showed marked increase in neurons and nerve bundles in the
      submucosa. Although there were no syndromic features or a positive family
      history, mutation analysis of the RET proto-oncogene showed a de novo germline
      Met918Thr mutation in both patients, confirming the diagnosis of multiple
      endocrine neoplasia type 2B (MEN 2B). Thyroidectomy was performed at 9 and 14
      months, showing medullary carcinoma and focal prominent C-cell hyperplasia,
      respectively. These 2 cases are presented to emphasize that when the submucosal
      plexus is obviously and prominently increased in suction rectal biopsies, diffuse
      intestinal ganglioneuromatosis should be considered. As this can be associated
      with genetic conditions, especially MEN 2B, it is crucial that further
      investigations be performed to ensure proper patient management, such as early
      thyroidectomy.

PMID- 16808643
TI  - Aneurysmal bone cysts express vascular markers.
AB  - Recently, clonal chromosome abnormalities have been identified in the mural
      spindle cells in aneurysmal bone cysts (ABCs), but the nature of the cystic
      spaces is unclear. Endothelial injury has been suggested as a mechanism of
      aneurysmal formation in these lesions, but few studies have surveyed vascular
      markers in ABCs. We stained 25 primary aneurysmal bone cysts with a variety of
      antibodies that stain vessels. Antibody to factor 8 stained the edge of ABC
      cavities in almost all cases, and antibodies to VEGF-C, GLUT-1, and smooth muscle
      actin stained the edge of the cavities in approximately half the cases.
      Antibodies to D2-40 and CD34 also stained the edge of the cavities in some cases.
      These results suggest that the cavities in ABCs are related to vasculature and
      support the theory that vascular injury may be important in the pathogenesis of
      ABCs.

PMID- 16808644
TI  - Umbilical cord hypercoiling and thinning: a rare cause of intrauterine death in
      the second trimester of pregnancy.
AB  - Little attention has been paid to the pathologic features of the umbilical cord,
      which might fatally damage the fetus. We determined the association of
      hypercoiling (more than 1 coil per 5 cm) and thinning with consecutive
      constriction of the umbilical vessels (thin cord syndrome; TCS) and intrauterine
      fetal death (IUFD). Three hundred and three cases of consecutive fetal autopsies
      over a 5-year period, including spontaneous and induced abortions of the 2nd
      trimester of pregnancy, were examined using a standardized protocol. The mean
      maternal age was 28.5 years and the mean gestational age was 19.1 weeks (range:
      12.6 to 24.5 weeks). Thirty-six percent of all cases were induced abortions
      because of congenital malformations, and 8.9% resulted from legal abortions, as
      regulated by German law. One hundred sixty-seven cases (55.1%) were spontaneous
      abortion specimens. The leading cause for IUFD in the spontaneous abortion group
      was an amnion infection (34.7%), followed by abruptio placentae (15.6%). In 25.1%
      of cases, placental dysmaturity with consecutive placental insufficiency was
      responsible for IUFD. Pathologies of the umbilical cord as the cause of IUFD were
      seen in 10.2% of the cases. Most of these cases (15/17) involved TCS. In 14.4% of
      all spontaneous abortion specimens the cause of IUFD could not be determined by
      autopsy. There was an apparent difference in the frequency of TCS in the
      spontaneous abortion group (15/167 = 9%) compared to the nonspontaneous group
      (2/136 = 1.5%). A remarkably high percentage (17/303 = 5.6%) of all cases showed
      TCS. In cases of spontaneous abortions, TCS was causative for intrauterine death
      in 9% of cases (15/167). Careful pathologic examination of the umbilical cord is
      recommended to detect TCS and to reduce the cases with unexplained intrauterine
      death.

PMID- 16808645
TI  - Technology: law of accelerating returns.

PMID- 16808646
TI  - Use of stents after ureteroscopic stone removal.

PMID- 16808647
TI  - Case report: the stone-basket nidus.
AB  - A 55-year-old man presented with intermittent right-flank pain 6 months after
      ureteroscopic stone extraction with holmium laser lithotripsy. A distal-ureteral
      stone was removed that contained fragments of a stone basket. Diligent inspection
      of endourologic accessories is critical to ensuring no fragments are left in
      patients, especially when a laser has been used.

PMID- 16808648
TI  - Laparoscopy-assisted ileal ureter creation for multiple tuberculous strictures:
      report of two cases.
AB  - We describe in detail the technique of laparoscopy-assisted ileal ureter creation
      for multiple tuberculous ureteral strictures in two patients. The proximal
      anastomosis included an ileocalicostomy in the first patient and an
      ileopyelostomy in the second patient. The first patient had bowel entrapment
      behind the mesentery of the ileal loop, but the second patient had an uneventful
      postoperative recovery. Short-term follow-up showed good patency of the ileal
      loop. The variations in the technique that can cause postoperative problems are
      discussed, and the future of this technique is postulated.

PMID- 16808649
TI  - Case report: laparoscopic management of massive chylous ascites after salvage
      laparoscopic retroperitoneal lymph-node dissection.
AB  - Chylous ascites is an infrequent complication of retroperitoneal surgery. We
      describe a patient who suffered massive chylous ascites after simultaneous
      pneumonectomy and laparoscopic excision of a post-chemotherapy tumor mass. After
      conservative management failed, exploratory laparoscopy identified the site of
      the leak, which was clipped and closed with fibrin glue. There has been no
      recurrence in the ensuing 5 years.

PMID- 16808650
TI  - Case report: bilateral hand-assisted laparoscopic nephrectomy in a patient with
      polycystic horseshoe kidney.
AB  - PURPOSE: To report the use of the hand-assisted laparoscopic (HAL) technique for
      removal of a horseshoe kidney in a patient with autosomal dominant polycystic
      kidney disease (ADPKD). CASE REPORT: Hospital and outpatient records were
      reviewed for a 65-year-old man with end-stage renal disease secondary to ADPKD
      who underwent HAL bilateral nephrectomy of his horseshoe kidney in preparation
      for kidney transplantation. The surgical method is described. It was completed
      successfully with an operative time of 280 minutes and an estimated blood loss of
      350 mL. CONCLUSION: Bilateral HAL nephrectomy can be considered as an option for
      surgical removal of very large polycystic horseshoe kidneys.

PMID- 16808651
TI  - Case report: laparoscopic resection of ureteral inverted papilloma.
AB  - Inverted papilloma of the ureter is a rare entity, often mistaken for malignancy
      during work-up. As such, many of these patients have been unnecessarily treated
      with nephroureterectomy. Herein, we describe a novel laparoscopic approach for
      the treatment of a ureteral inverted papilloma. To our knowledge, this approach
      is the first application of laparoscopy for the treatment of this lesion.

PMID- 16808652
TI  - Povidone-iodine sclerotherapy is ineffective in the treatment of symptomatic
      renal cysts.
AB  - PURPOSE: To evaluate the efficacy of povidone-iodine sclerotherapy after
      percutaneous drainage of simple renal cysts in the treatment of symptomatic
      patients. PATIENTS AND METHODS: Sixteen patients with symptomatic renal cysts
      were treated by percutaneous drainage and injection of povidone-iodine solution.
      The cysts were drained by a nephrostomy tube catheter, and povidone- iodine
      injections were repeated every 24 hours for 3 days. All patients were followed up
      by ultrasound examination during a period ranging from 1 to 4 years (mean 1.8
      years). RESULTS: Thirteen patients experienced recurrence of cysts, while
      complete resolution was observed in only three patients. Of the cysts that
      recurred, only partial resolution in cyst diameter was observed (from 3-10.5 cm
      to 2.4-8.6 cm). During the follow-up period, 12 of the 16 patients (75%)
      continued to have pain that necessitated additional treatments. CONCLUSION:
      Povidone-iodine sclerotherapy is followed by a high rate of recurrence and is
      therefore not indicated for the treatment of symptomatic simple renal cysts.

PMID- 16808653
TI  - Treatment of renal-vascular injury by transcatheter embolization: immediate and
      long-term effects on renal function.
AB  - PURPOSE: To evaluate the impact of superselective embolization for treatment of
      renal-vascular injuries on renal function. PATIENTS AND METHODS: Between 1995 and
      2004, four male patients and one female patient with a mean age of 45.4 years
      underwent embolization to control bleeding from renal-vascular injuries resulting
      from iatrogenic interventions (N = 4) or blunt abdominal trauma (N = 1).
      Angiography depicted a pseudoaneurysm in all patients, together with an
      arteriovenous fistula in one. Superselective embolization was achieved with 0.035
      or 0.018-inch coils combined with a mixture of Histoacryl and Lipiodol in one
      patient. RESULTS: Bleeding was controlled in all patients and did not recur. No
      complications occurred after the procedure. Hematuria ceased within 3 days. The
      serum creatinine concentration returned to pre-injury values within 10 days.
      Embolization caused an immediate parenchymal ischemic area of 0 to 20% (mean 9%).
      The contrast-enhanced CT scan 6 months after the procedure revealed a parenchymal
      perfusion deficit of 0 to 10% (mean 5%). CONCLUSIONS: Superselective embolization
      resulted in permanent cessation of bleeding. Renal function was preserved in all
      the patients, and serum creatinine concentrations returned to the pre-injury
      values. Transcatheter embolization should be considered the treatment of choice
      in the management of renal-vascular injuries.

PMID- 16808654
TI  - Acute dilatation of intramural ureter for ureteroscopy: railway technique.
AB  - PURPOSE: To assess the safety and efficacy of acute dilatation of THE intramural
      ureter for ureteroscopy by the railway technique. PATIENTS AND METHODS: Between
      January 2000 and December 2004, 400 consecutive ureteroscopic procedures were
      performed, among which 15 male and 5 female patients (5%) with an average age of
      40 years (range 25-65 years) underwent acute dilatation of the intramural ureter
      by the railway technique A guidewire is placed into the ureter, and a 3F ureteral
      catheter is passed through the working channel of the ureteroscope (8.5F-10F) for
      3 to 5 cm into the ureter. The ureteroscope is rotated so that it lies between
      the guidewire (outside) and the ureteral catheter (inside) and advanced between
      the guidewire and the ureteral catheter like riding over a railway.
      Postoperatively, no double-J stent was used. The mean follow-up was 25 months
      (range 6-60 months). An intravenous urogram and voiding cyctourethrography were
      obtained at 3 months, and ultrasonography was performed every 6 months in the
      first year and every 2 years after ureteroscopy in all 20 patients. RESULTS:
      Ureteral access was achieved with the railway technique in all 20 patients.
      Perforation or intramural false passage of the ureter did not appear. Follow-up
      imaging showed no distal-ureteral stricture or vesicoureteral reflux.
      CONCLUSIONS: Acute dilatation of the intramural ureter by the railway technique
      is cost effective, safe, easy, rapid, and predictable. This time-saving technique
      often removes the need for balloon dilatation of the distal ureter.

PMID- 16808655
TI  - Ureteroscopy for symptomatic hydrocalices: a case series.
AB  - BACKGROUND: Hydrocalix is an uncommon condition that typically is treated with
      percutaneous dilation of the stenotic infundibulum. Ureteroscopy has the
      advantage of minimizing invasiveness. METHODS: We reviewed our experience with 12
      retrograde ureteroscopies for hydrocalix in 10 patients. RESULTS: Access to the
      hydrocalix could not be achieved in one. Of the remaining 11, the original
      infundibulum was dilated in all but one, in whom neoinfundibulotomy was performed
      with a laser. The laser was used in eight cases, balloon dilation with cautery in
      two, and cautery alone in one. Of the seven hydrocalices bearing stones, four
      were rendered stone free. Immediate symptomatic success was achieved after 6 of
      the 11 evaluable procedures (one patient was lost to follow-up after a
      technically successful procedure). Of the five symptomatic failures, three went
      on to additional treatment (one ureteroscopy and two percutaneous), one elected
      against treatment despite recurrence of stenosis, and one had persistent pain
      owing to stones even though the hydrocalix was cured. Of the six symptomatic
      successes, three were without symptoms at a mean 25 months of follow-up, two have
      had recurrences necessitating additional treatment (both percutaneous) a mean of
      51 months later, and one did not have adequate imaging follow-up. CONCLUSION:
      Ureteroscopy for hydrocalix achieved technical success in most patients, but
      relief of symptoms followed only about half of the procedures. A trial of
      ureteroscopy does not preclude subsequent success with a percutaneous approach.
      Ureteroscopy is a reasonable option for hydrocalix for patients who wish to avoid
      percutaneous surgery.

PMID- 16808656
TI  - Comparison of flexible grasping forceps and stone basket for removal of retracted
      ureteral stents.
AB  - BACKGROUND: Ureteral-stent dislocation can occur either during positioning or
      postoperatively. Grasping the distal end of the stent and removing it depends on
      the angulation between the extraction device and the stent, the size and length
      of the instrument, and the force of the branches and resistance of the dislocated
      stent. PATIENTS AND METHODS: Six cases of challenging stent removal are
      presented, and details of the surgical technique are described. By in-vitro
      testing, we investigated the deflection of flexible cystoscopes and ureteroscopes
      using forceps or a four-wire stone basket, the ability to grasp a stent depending
      on the angle between the stent axis and the extraction device, and the force that
      can be applied on the stent with the different devices. RESULTS: In all cases, it
      was possible to extract the stent with a stone basket. In an in-vitro setting,
      maximum extraction forces, measured with a macro scale, were 1.3 kg (cystoscopic
      forceps) and 0.4 kg (ureteroscopic forceps) until the forceps slipped off the
      stent. In the same setting, a rupture of the wires of the 1.9F stone basket
      occurred at 0.8 kg, whereas with a 2.4F basket, a force of 1.9 kg led to rupture
      of the stent, leaving the basket intact. CONCLUSIONS: Using a stone basket
      instead of grasping forceps in difficult cases of dislocated stents opens new
      possibilities for their cystoscopic and ureteroscopic removal. Because the
      superiority of the basket is counterbalanced by its higher costs, we suggest the
      basket extraction method only in difficult cases.

PMID- 16808657
TI  - Forgotten ureteral stents causing renal failure: multimodal endourologic
      treatment.
AB  - PURPOSE: To report our experience in managing nine patients with forgotten
      ureteral stents that resulted in chronic renal failure (CRF). PATIENTS AND
      METHODS: We reviewed our stent records from January 1994 to January 2004 to
      analyze cases of forgotten indwelling ureteral stents in solitary kidneys that
      had led to CRF (serum creatinine 4-14 mg/dL). These patients had normal renal
      function prior to the interventions at which stents were placed. They were
      subjected to multimodal endourologic management, including cystolithotripsy and
      ureteroscopic and percutaneous lithotripsy, to make them stent and stone free in
      a single operative session. RESULTS: The median dwell time of the retained stents
      was 39 months. Three patients were not aware of the stent, while six chose to
      ignore it. All patients underwent a temporizing percutaneous nephrostomy with an
      8F pigtail catheter and were operated on 2 to 4 weeks later. All nine patients
      were rendered stone and stent free; however, one patient succumbed to septic
      complications 3 weeks after the operation. At last follow-up (6-56 months), two
      patients are on the transplant waiting list, while six are living with mild to
      moderate renal failure on conservative treatment. CONCLUSIONS: Chronic renal
      failure caused by encrusted stents in a functionally solitary kidney is a
      disastrous complication of forgotten stents. Prevention is, of course, ideal, but
      such cases are still seen despite increasing awareness. Temporizing percutaneous
      nephrostomy, renal support, and skilled endourologists are the cornerstones of
      management of such high-risk cases.

PMID- 16808658
TI  - Percutaneous suprapubic cystolithotripsy approach: for whom? Why?
AB  - BACKGROUND AND PURPOSE: To evaluate the success and complications of percutaneous
      suprapubic cystolithotripsy (PCCL) in pediatric and adult patients with
      neurogenic bladder. PATIENTS AND METHODS: Between 2000 and 2004, 72 patients, all
      male (30 children aged 2 to 7 years [mean 4.7 years] and 42 spastic paraplegic
      adults aged 34 to 62 years [mean 53 years]), with sterile urine underwent PCCL
      under general anesthesia in one sitting. An 18-gauge needle, Amplatz dilatation
      set, 30F Amplatz sheath, rigid nephroscope, lithotripter (pneumatic, mechanic),
      and stone forceps were used. Fluoroscopy was not. A suprapubic catheter was
      placed in the first two patients only. RESULTS: The dimensions of the stones were
      on average 3.2 cm (range 1-5 cm) for the pediatric patients and 5.5 cm (4-10 cm)
      for the adult patients. The operating time was 20 minutes (10-35 minutes). In all
      cases, the stones were taken out. No serious intraoperative or postoperative
      complications were observed. In all cases, the transurethral catheter was removed
      on postoperative day 5. No recurrence was observed during the follow-up period
      (mean 20 months). CONCLUSION: As urethral diameters are narrow in pediatric
      patients and adult spastic paraplegic patients in whom an endoscopic approach
      could not be performed, PCCL is a safe alternative with low morbidity and
      complication rate. The technique is also more advantageous than open surgery with
      regard to cosmetic outcome and length of the hospital stay.

PMID- 16808659
TI  - Case report: endoscopic management of seminal vesicle stones with cutaneous
      fistula.
AB  - Stones in the seminal vesicle are rare. Open surgery to remove either the seminal
      vesicle or the stone usually is required. We report a case of seminal-vesicle
      stones compounded by cutaneous fistula that was treated by ureteroscopy,
      intracorporeal lithotripsy, and fulguration of the fistulous tract.

PMID- 16808660
TI  - Case report: tubercular cold abscess of seminal vesicle: minimally invasive
      endoscopic management.
AB  - BACKGROUND: Tubercular cold abscess of the seminal vesicle is very rare, and only
      a few cases are reported in literature. Preoperative diagnosis is difficult and
      to the best of our knowledge has not been reported. CASE REPORT: A 35-year-old
      man presented with a 7-year history of blood in the semen and a reddish brownish
      discharge per urethra while defecating. On rectal examination, a soft fluctuant
      mass was felt above the prostate. Abdominal ultrasonography showed cystic
      swelling of the right seminal vesicle bulging into the posterior bladder wall.
      Semen examination showed abundant pus cells and 90% immotile sperm with normal
      morphology. Acid-fast bacilli were not seen, but acid-fast bacilli were found in
      a 24-hour urine specimen. Cystoscopy showed tubercles in the urethra and brownish
      discharge from the orifice of the right ejaculatory duct on per-rectal
      compression of the mass. The abscess cavity was incised with a Collings' knife.
      Brownish material was evacuated, and the abscess cavity was seen. An 18F Foley
      catheter was placed for 3 days. Antitubercular therapy was instituted.
      Ultrasonography repeated after 3, 25, 45, and 75 days showed gradual regression
      of the abscess cavity. Semen examination after 75 days was normal, with 75%
      motility, and cystoscopy 45 days postoperatively showed complete healing of the
      wound. CONCLUSION: The incision connecting the bladder with the abscess cavity
      facilitated evacuation of pus and complete resolution of the abscess.

PMID- 16808662
TI  - Re: Aghamir SMK et al: Use of surgicel for sealing nephrostomy tract after
      totally tubeless percutaneous nephrolithotomy.

PMID- 16808668
TI  - Measurement of skin desmosine as an indicator of altered cutaneous elastin in
      draft horses with chronic progressive lymphedema.
AB  - BACKGROUND: Chronic progressive lymphedema in Clydesdale and Shire draft horses
      causes severe disability of the limbs which leads to premature death of these
      horses. Since appropriate function of lymph vessels is dependent on the presence
      of viable elastin fibers, the goal of this study was to document differences in
      skin elastin fibers in affected horse breeds, compared to a nonaffected draft
      horse breed. METHODS AND RESULTS: Biochemical analysis of cutaneous desmosine, a
      cross-linking amino acid found only in elastin, was used to measure elastin in
      the skin from 110 draft horses. This included 7 normal, 38 mildly affected, 30
      moderately, and 15 severely affected horses, and 20 horses of a nonaffected draft
      breed. Desmosine concentrations in neck, considered a nonaffected skin region,
      and left forelimb, an affected skin region, were compared between the groups. A
      significantly lower desmosine concentration was found in the skin of the neck and
      limb of clinically normal animals of affected draft breeds compared to a
      nonaffected draft horse breed. During the progression of the disease in the
      affected breeds, cutaneous desmosine concentrations most prominently increased in
      the skin of the distal limbs. CONCLUSIONS: Chronic progressive lymphedema in
      draft horses was associated with an initially systemic lower cutaneous elastin
      level and a deposition of elastin during the progression of the disease. A
      failure of elastic fibers to appropriately support the skin and its lymphatics is
      proposed as a possible contributing factor for chronic progressive lymphedema in
      Shires and Clydesdales.

PMID- 16808669
TI  - Vascular endothelial growth factor-C (VEGF-C) expression in normal human tissues.
AB  - OBJECTIVE: To characterize vascular endothelial growth factor-C (VEGF-C) protein
      expression in normal human tissues by immunohistochemistry (IHC). VEGF-C is a
      growth factor for lymphatic endothelial cells. VEGF-C mRNA and protein are
      expressed in a variety of cancerous tissues, but the localization of VEGF-C
      protein in many normal human tissues has not been clearly demonstrated to date.
      We therefore performed an immunohistochemical survey of the distribution of
      intracellular VEGF-C protein in a range of normal human tissue types. METHODS:
      Five microm sections were cut from archived human tissues. Sections were dewaxed,
      rehydrated, and subjected to microwave pretreatment. They were incubated with
      VEGF-C antibody before detection with biotinylated secondary antibody using
      'Elite' avidin-biotin enzyme complex and diaminobenzidine substrate. The primary
      antibody recognized the C-terminus of the VEGF-C propeptide that is cleaved
      before secretion and hence only cellular protein was detected. Negative controls
      used the same concentration of normal goat IgG. RESULTS: Staining manifested as
      small punctate cytoplasmic granules. Strong expression was observed in large
      intestine epithelium, and mammary duct epithelium, skeletal and cardiac muscle,
      thyroid, ovary, and the prostate. Weaker expression was also detected in the
      hepatocytes close to the terminal hepatic venules of the liver, vascular smooth
      muscle, and placenta. No expression was consistently detected in spleen or
      thymus. CONCLUSIONS: Intracellular VEGF-C protein is widely expressed in many
      normal human adult tissues. Its expression in cancer is not therefore per se
      indicative of a prolymphangiogenic change. To demonstrate the latter, a
      quantitative change in expression level is required.

PMID- 16808670
TI  - Lymphatic endothelial cells, lymphangiogenesis, and extracellular matrix.
AB  - Exciting studies involving the molecular regulation of lymphangiogenesis in
      lymphatic-associated disorders (e.g., wound healing, lymphedema and tumor
      metastasis) have focused renewed attention on the intrinsic relationship between
      lymphatic endothelial cells (LECs) and extracellular matrix (ECM)
      microenvironment. ECM molecules and remodeling events play a key role in
      regulating lymphangiogenesis, and the "functionality"-relating molecules,
      especially hyaluronan, integrins, reelin, IL-7, and matrix metalloproteinases,
      provide the most fundamental and critical prerequisite for LEC growth, migration,
      tube formation, and survival, although lymphangiogenesis is directly or/and
      indirectly controlled by VEGF-C/-D/VEGFR- 3- Prox-1-, Syk/SLP76-, podoplanin/Ang
      2/Nrp-2-, FOXC2-, and other signaling pathways in embryonic and pathological
      processes. New knowledge regarding the differentiation of initial lymphatics
      should enable improvements in understanding of a variety of cytokines,
      chemokines, and other factors. The lymphatic colocalization with histochemical
      staining by using the novel molecular markers (e.g., LYVE-1), along with
      subsequent injection technique with ferritin or some tracer, will reveal
      functional and structural features of newly formed and preexisting lymphatics.
      Growing recognition of the multiple functions of ECM and LEC molecules for
      important physiological and pathological events may be helpful in identifying the
      crucial changes in tissues subjected to lymph circulation and ultimately in the
      search for rational therapeutic approaches to prevent lymphatic-associated
      disorders.

PMID- 16808671
TI  - CO2 laser ablation of lymphangioma circumscriptum of the scrotum.
AB  - Lymphangioma circumscriptum (LC) is an uncommon skin condition characterized by
      large muscular-coated lymphatic cisterns that lie deep with in the subcutaneous
      tissue and communicate with dilated dermal lymphatics. Patients suffer from edema
      and lymphatic leakage. Surgical excision and reconstruction is the gold standard
      for therapy. However, this can be mutilating. The authors present a patient who
      suffered widespread disease of his scrotum who had excellent symptomatic relief
      by treatment with the CO(2) laser.

PMID- 16808675
TI  - Comparison of ketorolac tromethamine, diclofenac sodium, and loteprednol
      etabonate in an animal model of ocular inflammation.
AB  - PURPOSE: The aim of this study was to compare the anti-inflammatory activities of
      ketorolac tromethamine 0.4% and 0.1%; diclofenac sodium 0.1%; and loteprednol
      etabonate 0.5% suspension in an animal model of ocular inflammation. METHODS: An
      ocular inflammatory response was induced in New Zealand White rabbits by the
      intravenous (i.v.) administration of 10 microg/kg lipopolysaccharide (LPS). In
      study animals, 1 eye was treated topically with 50 microL of study medication (n
      = 8 animals per drug) and the other eye was treated topically with a 50-microL
      vehicle (buffered saline). In control animals (n = 8), both eyes were treated
      with vehicle. All animals were treated twice: 2 h and 1 h before LPS challenge.
      The breakdown of the blood-aqueous barrier in the anterior chamber was measured
      by fluorophotometry (FITC-dextran 30 mg/kg, i.v. given immediately after LPS
      challenge). Aqueous prostaglandin E(2) (PGE(2)) levels were measured using an
      enzyme-linked immunosorbent assay (ELISA) immunoassay. RESULTS: Ketorolac 0.4%
      resulted in a nearly complete inhibition of endotoxin-induced increases in FITC
      dextran and PGE(2) synthesis (P < 0.001 vs. vehicle). Diclofenac 0.1% had much
      less of an effect on these parameters (P < 0.01 vs. ketorolac 0.4%). Loteprednol
      0.5% was no more effective than vehicle at inhibiting increases in FITC-dextran.
      CONCLUSIONS: Ketorolac has greater anti-inflammatory effects than diclofenac and
      loteprednol.

PMID- 16808676
TI  - Ocular hypotensive effects of an intratracheally delivered liposomal delta9
      tetrahydrocannabinol preparation in rats.
AB  - This study investigated the effect of an intratracheal (i.t.) administration of a
      liposome-entrapped Delta9-tetrahydrocannabinol (LTHC) preparation on intraocular
      pressure (IOP) in nonanaesthetized Brown Norway rats. The ocular hypotensive
      effects of i.t. LTHC were compared to that of intraperitoneal (i.p.) LTHC
      administration. All i.t. LTHC doses >0.05 mg/kg significantly decreased IOP (P <
      0.05) within 30 min of administration, and doses of i.t. LTHC >0.1 mg/kg
      decreased IOP within 15 min of administration. A maximal reduction in IOP of 2.32
      +/- 0.27 mmHg (n = 4) was seen with 1.0 mg/kg of i.t. LTHC. In comparison, no
      significant IOP drop was apparent prior to 30 min with all doses (0.01-1.0 mg/kg)
      of i.p. LTHC tested, although a similar maximum drop in IOP (2.15 +/- 0.12 mmHg;
      n = 8) was obtained with 1.0 mg/kg of LTHC. The ED(50) for i.t. and i.p. LTHC was
      0.08 mg/kg and 0.12 mg/kg, respectively. The IOP-lowering effects of i.p. LTHC
      (0.2 mg/kg) were reduced by 14% and 80% by 0.25 mg/kg (n = 6) and 2.5 mg/kg (n =
      6), respectively, of the CB1R antagonist, SR141716A. In conclusion, i.t. LTHC was
      superior to i.p. LTHC in producing a more rapid and potent decrease in IOP. The
      IOP-lowering effect of LTHC was blocked by the CB1R-selective antagonist,
      SR141716A, suggesting that CB1Rs contribute to the ocular hypotensive effect of
      Delta9-tetrahydrocannabinol.

PMID- 16808677
TI  - Mycophenolate mofetil as an immunosuppressive agent in refractory inflammatory
      eye disease.
AB  - PURPOSE: The aim of this study was to assess the role of mycophenolate mofetil
      (MMF) in refractory inflammatory eye disease. METHODS: Retrospective,
      noncomparative, interventional case series of all patients commenced on MMF
      between 1999 and 2005 for refractory inflammatory eye disease at St Paul's Eye
      Unit (Liverpool, UK). Main outcome measures noted were control of inflammation,
      steroid-sparing effect, and adverse effects of MMF therapy. RESULTS: Ten (10)
      patients (2 with sarcoid, 2 with intermediate uveitis, 1 with Vogt-Koyanagi
      Harada (VKH) syndrome, 1 with ankylosing spondylitis, 1 with juvenile chronic
      arthritis (JCA), and 3 with scleritis) who were unresponsive or intolerant to
      previous therapy and/or as a steroid-sparing agent, received 2-3 g of MMF per day
      for a mean period of 40.5 months (range, 3-67). Nine (9) patients had a favorable
      response, with diarrhea and insomnia being the main side-effects. MMF had to be
      withdrawn in 1 patient because of side-effects and in another because of active
      arthropathy (with stable uveitis). Average number of relapses was reduced from
      3.1 per patient per year to 0.8 per patient per year (P < 0.005). A steroid
      sparing effect was achieved in all patients. Visual acuity improved in 8
      patients. CONCLUSIONS: MMF appears to be a safe and effective second- or third
      line adjunct/alternative immunosuppressant in these difficult cases and works
      well in combination with cyclosporin A, tacrolimus, and antitumor necrosis factor
      (TNF) agents. It has potential as a firstor second-line agent and can be
      considered at a dose of 3 g/day in refractory cases.

PMID- 16808678
TI  - Brimonidine 0.2% versus brimonidine Purite 0.15%: prophylactic effect on iop
      elevation after Nd:YAG laser posterior capsulotomy.
AB  - AIMS: The aim of this study was to compare the prophylactic effect of brimonidine
      0.2% versus brimonidine Purite 0.15% on intraocular pressure (IOP) increase after
      Nd:YAG laser posterior capsulotomy. METHODS: In this prospective, double-masked,
      randomized, controlled study, 106 patients (106 eyes) who underwent Nd:YAG laser
      posterior capsulotomy were allocated to a brimonidine 0.2% group (35 eyes), a
      brimonidine Purite 0.15% group (36 eyes), or a vehicle group (35 eyes). One (1)
      drop of brimonidine 0.2%, brimonidine Purite 0.15%, or vehicle was instilled 1 h
      preoperatively and 1 drop immediately after Nd:YAG laser posterior capsulotomy.
      IOPs were measured preoperatively and at 1, 2, 3, and 24 h postoperatively.
      RESULTS: Decreases in IOP from baseline ranged from 2.3 to 2.7 mmHg in the
      brimonidine 0.2% group and 2.2-2.5 mmHg in the brimonidine Purite 0.15% group (P
      < 0.05), whereas the vehicle group exhibited a rise in IOP. IOP elevations of
      less than 5 mmHg occurred in 22.9% of patients in the brimonidine 0.2% group,
      27.8% in the brimonidine Purite 0.15% group, and 48.6% in the vehicle group.
      Spikes of IOP greater than 10 mmHg occurred in 2.9% of patients in the
      brimonidine 0.2% group, 2.8% in the brimonidine Purite 0.15% group, and 8.6% in
      the vehicle group. The incidence of IOP elevation was not statistically
      significant between the brimonidine 0.2% and the brimonidine Purite 0.15% groups
      (P < 0.05). CONCLUSIONS: Brimonidine 0.2% and brimonidine Purite 0.15% have
      similar efficacy in the prevention of IOP elevation after Nd:YAG laser posterior
      capsulotomy.

PMID- 16808679
TI  - Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of
      horner syndrome in pediatric patients.
AB  - PURPOSE: The aim of this study was to compare the efficacy of 0.5% apraclonidine
      with that of 4% cocaine and to evaluate its safety in the diagnosis of Horner
      syndrome in pediatric patients. METHODS: This was a randomized, crossover study,
      wherein 10 patients with a probable diagnosis of Horner syndrome were assigned to
      undergo pharmacological testing with 4% cocaine and 0.5% apaconidine. The
      difference in the pupil diameters of each eye was recorded under dim light before
      and 1 h after 0.5% apraclonidine or 4% cocaine was instilled. Any adverse effects
      were noted during examination or reported by the patients' parents were recorded.
      RESULTS: The mean differences in pupil diameter before and after 4% cocaine
      testing were -2.08 and -2.97 mm, respectively (P = 0.0047). All patients had an
      anisocoria greater than 1 mm after 4% cocaine testing. The mean difference in
      pupil diameter before and after 0.5% apraclonidine was instilled were -2.04 and
      +1.08 mm, respectively (P = 0.005). All patients showed a reversal of anisocoria
      after 0.5% apraclonidine testing. Conjunctival hyperemia was noted in 2 patients,
      but systemic adverse effects were not noted during examination nor reported by
      the patients' parents. CONCLUSIONS: The application of 0.5% apraclonidine in
      pediatric patients is safe and effective in the diagnosis of Horner syndrome.

PMID- 16808680
TI  - Effects of bimatoprost 0.03% on ocular hemodynamics in normal tension glaucoma.
AB  - PURPOSE: The aim of this study was to investigate the effects of bimatoprost
      0.03% on ocular hemodynamics in patients with normal tension glaucoma (NTG).
      METHODS: Twenty-two (22) patients with NTG were consecutively recruited. After
      basic eye examination and diurnal intraocular pressure (IOP) measurement, color
      Doppler imaging was used to measure the peak systolic and end diastolic
      velocities and resistive index of the central retinal, lateral posterior ciliary,
      and medial posterior ciliary arteries. Patients received bimatoprost 0.03% for 4
      weeks, and these measurements were then repeated. The worse eye of each NTG
      patient was used in the statistical analysis. RESULTS: Bimatoprost 0.03%
      significantly reduced mean IOP from 15.1 +/- 3.8 mmHg at baseline to 12.0 +/- 2.9
      mmHg after treatment in our sample of NTG patients (P < 0.001). No significant
      changes in blood velocities or resistance indices were observed in the
      retrobulbar vessels after the 4-week treatment. CONCLUSIONS: Topical bimatoprost
      0.03% significantly reduced IOP in our NTG patients without causing significant
      hemodynamic changes in the retrobulbar vessels.

PMID- 16808681
TI  - Duration of the effect of intravitreal triamcinolone acetonide in eyes with
      exudative age-related macular degeneration.
AB  - OBJECTIVE: The aim of this study was to evaluate the duration of the effect of an
      intravitreal injection of approximately 20 mg of triamcinolone acetonide (TA) on
      visual acuity and intraocular pressure (IOP) in patients with exudative age
      related macular degeneration (AMD) with subfoveal choroidal neovascularization.
      PARTICIPANTS: The prospective, clinical, interventional, case series study
      included 69 patients (71 eyes) with exudative AMD who showed an increase in
      visual acuity by at least 2 Snellen lines after an intravitreal injection of
      approximately 20 mg TA. Mean follow-up was 11.5 +/- 7.4 months (3.3-35.7 months).
      The main outcome measure was visual acuity. RESULTS: Within the first week after
      the injection, visual acuity and IOP started to increase significantly (P <
      0.001) by reaching a plateau-like maximum at 1-6 months after the injection.
      Visual acuity and IOP returned to baseline values 7-9 months after the injection.
      Increase of IOP was statistically (P = 0.72) independent of the change in visual
      acuity. CONCLUSIONS: In patients with exudative AMD, who have shown an increase
      of at least 2 Snellen lines in visual acuity, the effect of intravitreal TA
      (dosage approximately 20 mg) lasts 7-9 months with respect to an increase in
      visual acuity and IOP.

PMID- 16808682
TI  - Intravitreal triamcinolone acetonide for diabetic macular edema: a prospective,
      randomized study.
AB  - PURPOSE: The aim of this study was to examine the visual outcome of patients
      receiving an intravitreal injection of triamcinolone acetonide (TA) as treatment
      of diffuse diabetic macular edema (DDME). METHODS: This prospective, placebo
      controlled, randomized, clinical interventional study included 40 eyes (38
      patients) with DDME, with 28 (70%) eyes randomized to treatment and 12 (30%) eyes
      randomized to receive a placebo injection. Thirty-six (36) (90%) eyes completed
      the 3-month study visit, and 32 (80%) eyes completed the 6-month study visit. The
      treatment group received an intravitreal injection of approximately 20 mg of TA.
      RESULTS: Visual acuity increased significantly (P < 0.001) in the study group by
      3.4 +/- 2.5 Snellen lines. In the control group, visual acuity did not change
      significantly (P = 0.07) during follow-up. Difference in change of best visual
      acuity was significant (P < 0.001) between both groups. At 3 months after
      baseline, 11 (11/26; 42%) eyes and 10 (10/26; 39%) eyes, respectively, improved
      by at least 2 and 3 lines, respectively, in the study group, versus 2 (2/10; 20%)
      eyes and 1 (1/10; 10%) eye in the control group. At 6 months after baseline, 11
      (11/23; 48%) eyes and 9 (9/23; 39%) eyes, respectively, improved by at least 2
      and 3 lines, respectively, in the study group, versus 0 (0%) eyes and 0 (0%) eyes
      in the control group. The difference was significant for the 2-line improvement
      (P = 0.01) and 3-line improvement (P = 0.03). CONCLUSIONS: Using a dosage of
      approximately 20 mg of intravitreal TA, visual acuity temporarily increases for 6
      months after injection.

PMID- 16808683
TI  - Persistent conjunctivitis associated with drinking arsenic-contaminated water.
AB  - PURPOSE: The aim of this study was to report on 2 cases of bilateral chronic
      conjunctivitis that were associated with the drinking of arsenic-contaminated
      underground water for a long time. DESIGN: Interventional case reports comprised
      the study. METHODS: This study was a review of clinical data and laboratory
      investigations. RESULTS: Papillary conjunctivitis developed in 2 members of a
      family who has been drinking underground water for 15 years. There were severe
      dermatological changes, including hyperkeratosis, on palms and soles, hypo- and
      hyperpigmented lesions (rain-drop) on the abdomen, chest, and back. Arsenic
      levels estimated in the nails and hair of both patients were very high. The
      arsenic level of the drinking water was above the permissible limit.
      Histopathological examination of conjunctival tissue confirmed the inflammatory
      response of a papillary type; however, an arsenic estimation in conjunctival
      tissue was not possible. There were no inclusions of bodies in conjunctival
      smears stained with hematoxylin and eosin (H&E) stain. There was no response to
      the usual treatment for papillary conjunctivitis, which only subsided, along with
      a regression of dermatological changes, when patients were treated with the
      chelating agent, dimercaprol, and multivitamin preparations, as well as no longer
      drinking the contaminated water. CONCLUSIONS: This is a rare association and, to
      the best of our knowledge, the first report of successful treatment with
      dimercarpol. The source of arsenic was contaminated underground drinking water
      (from a deep tube-well). The pathophysiology is thought to be the result of an
      inflammatory response caused by accumulated arsenic in local tissues. Papillary
      conjunctivitis and dermatological changes can be successfully managed with
      dimercaprol and multivitamins. Further studies are required to find out the
      possible link between the papillary response of conjunctiva and arsenic
      accumulation within the body.

PMID- 16808684
TI  - Towards a communicative mentality in medical and healthcare practice.

PMID- 16808685
TI  - The discursive construction of competence and responsibility in medical collegial
      talk.
AB  - The paper explores the construction of clinical competence in the spoken
      discourse of physicians. The analysis is derived from transcribed recordings of
      physicians' talk in the specialty of Haematology in an American teaching
      hospital. It is argued that current discussions of 'competence' among medical
      sociologists and anthropologists are not adequately based in the direct
      observation and recording of physicians' professional, collegial interactions. It
      is argued that physicians' constructions of case narratives and presentations
      inscribes the evaluations of the responsibility and competence of other
      physicians, through the representation of their agency and character in the
      course of accounts of cases. The paper thus addresses the naturally occurring use
      of 'evidence' in a clinical setting, and is an invitation to more naturalistic
      studies of 'evidence-based medicine'.

PMID- 16808686
TI  - Space, repetition and collective interlocution: Psychiatric interviews in a
      Borneo longhouse.
AB  - An analysis is presented of psychiatric research interviews conducted among the
      Iban, a longhouse dwelling people of Sarawak, Malaysia. It draws on transcripts
      of interviews recorded in the course of carrying out research into schizophrenia
      in this group. The article examines three different interview spaces within the
      longhouse--public, family, and private--in order to explore the interplay between
      ethnographic context and interview conversation. The public setting is notable
      for the number of relatives who join in and transform the communication from
      dyadic to collective interlocution; the role of repetition in recruiting them
      into the conversation is explored. Indirect contrast is the private space, which
      allows for a level of confidentiality commensurate with Western psychiatric
      research practice. Intermediate between the two is the family space. The
      communicative forms that correspond to these settings influence the way symptoms
      of schizophrenia are experienced and expressed in the Iban. Implications for the
      practice of psychiatry cross-culturally are examined.

PMID- 16808687
TI  - Cognitive overload and communication in two healthcare settings.
AB  - The confluence of organizational social interaction and cognitive information
      processing constraints create 'noisy' conditions in institutionalized settings.
      Attentional and memory limitations always influence the ability of participants
      to comprehend each other's communication. Two organizational settings (a medical
      specialty clinic and periodontal office) will be used to explore a few features
      of healthcare delivery that are often ignored in studies of such systems.
      Scheduling appointments, for example, creates stress for both patients and
      healthcare personnel but is often an unexamined aspect of healthcare delivery
      that has become both challenging and often irritating for all concerned. For
      example, when patients call, someone at a general scheduling center or the
      particular clinic or office of an individual physician or dentist or a group
      practice will answer the call with a menu of options, or the caller may be asked
      to leave message. When a patient leaves a clinic or surgery office after a visit,
      they may be allowed to make a new appointment. The term 'cognitive overload' is a
      ubiquitous element of all healthcare systems and refers to organizationally
      induced and constrained limited capacity processing inherent in the way
      improvised discourse practices, and annotative devices or artifacts (such as
      written notes or some related strategy) become an integral part of everyday
      healthcare delivery.

PMID- 16808688
TI  - Thirty-five voices in search of an author: what focus groups reveal about
      patients experiences in managed care settings.
AB  - Surprisingly little direct information from patients is available in the medical
      literature. Focus groups, which came into use in the 1940s, provide a simple,
      cost effective way of exploring attitudes and values within market segments or
      targeted groups. In healthcare, focus groups are being used to track patients'
      experiences, expectations and satisfaction in order to optimize quality and cost
      effectiveness. This study reports on a collaboration of three upstate New York
      Health Maintenance Organizations (HMOs) that used the same focus group format and
      questions to identify' best practices' and opportunities for improvement.
      Participants across groups reported similar experiences despite differences in
      geography and plan organization. Members' most positive comments were about
      costs, preventive services, ease of paper work and access to sick care, all
      administrative functions of the health plans. The most negative focused on
      retaining one's physician, telephone access, providers' medical skills, provider
      behavior and notification of results, all related to interpersonal/communication
      issues. We conclude that focus groups are useful for understanding and responding
      to the 'voice of the customer'. They also have some distinct advantages over
      forced-choice questionnaires, especially in trying to discover the range of
      patients' experiences and expectations, though they are not without their
      challenges.

PMID- 16808689
TI  - Symptoms and signs in particular: the influence of the medical concern on the
      shape of physician-patient talk.
AB  - Talk between physicians and their patients has been shown to be shaped by
      participant characteristics,phase of the visit, and professional and
      institutional constraints. Surprisingly, the medical concern that brings the
      participants together has not been systematically and thoroughly investigated as
      a shaping influence on such talk. Based on a synthesis of separate interactional
      sociolinguistic studies of ten different medical concerns involving 395 patients
      and 105 physicians, I identify seven major differences across medical issues that
      may shape physician-patient discourse. In this paper I then focus on the first of
      these seven--the indication of the medical problem. Beginning with the
      traditional medical distinction between symptoms and signs, I characterize the
      kinds of evidence introduced by physicians and patients in talk about medical
      concerns. I then turn to the fuller discourse context of these reports,
      specifically examining how the indications emerge and play themselves out in the
      visit. Following Becker (1995b), I identify a two-step 'attunement' process, in
      which one participant (1) uses language to move toward a clearer understanding of
      the other's evidence and then displays this emerging understanding, and (2) takes
      up a stance toward the other's evidence--either corroborating or dismissing it
      with evidence of his or her own. In closing, I argue the importance of
      considering the shaping influences of differences across medical concerns, both
      for discourse analysts in their quest to account for particularities within
      physician-patient discourse as well as for healthcare professionals who believe
      that more attuned communication practices can result in better medical practices.

PMID- 16808690
TI  - Joint working relationships: children, parents and child healthcare nurses at
      work.
AB  - In child healthcare children's development is examined and assessed. The main aim
      of this article is to explore the different ways in which a child health nurse
      establishes joint working relationships with children and parents. Few studies in
      child healthcare include nonverbal interaction. It was found that a child often
      responds to the actions of the nurse and the parent by physical and bodily
      actions and by the direction of his/her gaze. The nurse has to be able to shift
      between several different interactional modes using various nonverbal
      communicative means. She uses her body to shift positions together with shifts in
      gaze in order to establish an interactional focus and a relationship with the
      child. The nurse also uses different artifacts in the room as well as the child's
      spontaneous activities during the assessment of the child's development. In
      addition, she uses the parents' relationships with their children in order to
      gain their support and to encourage their children in performing tasks. An
      important methodological consequence of this study is that it is necessary to use
      video-recorded data when interactions of this kind are analyzed.

PMID- 16808691
TI  - Speaking about dying in the intensive care unit, and its implications for
      multidisciplinary end-of-life care.
AB  - This article addresses how professionals working in an intensive care unit in
      Australia speak about dying, with particular reference to the contradictions and
      complexities that characterize their work in this setting. The article reflects
      on the incommensurabilities in these clinicians' talk, and the consequences of
      this for how different professionals work together and care for extremely ill
      patients. Examples are drawn from talk recorded during ward rounds and focus
      groups. The article argues that intensive care units are settings where being
      reflexive about one's work and assumptions is especially difficult because it
      involves negotiating decisions and taking moral responsibility for decisions
      affecting very sick patients. These decisions and responsibilities put into sharp
      relief the 'wicked problems and tragic choices' of end-of-life existence and of
      intensive care in specific. This article shows some of the complex ways in which
      specific clinicians' discourse absorbs and manifests these tensions and
      responsibilities. The article concludes that these kinds of complexities are
      unlikely to be resolved with reference to formal knowledge or in-principle
      conviction, and that a new interactive basis needs to be found where clinicians
      can rehearse alternative ways of speaking with which to approach each other, the
      dying, and their families.

PMID- 16808692
TI  - The unjust world problem: Towards an ethics of advocacy for healthcare providers
      and researchers.
AB  - This article addresses the problem of the relative lack of connection between two
      ethical perspectives in the healthcare field: an ethics of humane care and an
      ethics of social justice. The first underlies the critique by practitioners and
      researchers of differentials between healthcare providers and patients in the
      irrespective levels of control over communication and collaboration in clinical
      encounters. The second informs the critique by public health researchers and
      policy makers of the structural basis of social inequality, poverty, and violence
      that are the sources of racial, ethnic and class differentials in levels of
      health. I have framed these two perspectives in a way that suggests their
      parallel concerns with inequality. By referring to a disconnect between them as
      the 'unjust world problem', I wish to mark their respective limitations--the
      first tending to exclude forces that lie outside the clinical situation and the
      second tending to ignore differentials in access to care and types of treatment
      received. I argue for the importance of bringing these two perspectives together
      in a dialectical relationship, where each informs and strengthens the other.
      Readers of this journal are familiar with studies of communication, clinical
      practice, and the humane care ethics and, therefore, I highlight studies
      undertaken within a social justice perspective that document marked disparities
      among social groups in rates of illness and preventable deaths and also refer to
      some models of work that link the two perspectives. These are complex issues and
      by suggesting that we consider an ethics of advocacy that is attentive to both
      humane care and social justice, I hope to raise questions for further discussion,
      such as: When we learn to communicate better and to listen to our patients and
      research subjects, will we be asking about and listening to their accounts of
      what it means to live in a world of poverty, social exclusion, and inequality?
      And if we then learn how their problems are rooted in such a world, are we
      prepared to become advocates with them not only for more humane health care but
      for social justice?

PMID- 16808694
TI  - Multilingualism and healthcare in Nigeria: a management perspective.
AB  - Nigeria has a healthcare system that has been described as defective even by its
      managers. A year 2000 study by the World Health Organization (WHO) of health
      systems in 191 member countries ranked Nigeria 187th. These several evaluations
      consistently point to inadequate managerial skills. Regrettably, very little is
      known of the import of language and communication as management issues in
      healthcare delivery in this country of 400 languages. This article therefore
      proposes a language-driven audit of health management in Borno State (northeast
      Nigeria) as a means of sensitizing policy makers and implementers. Based largely
      on data from questionnaires completed by 129 health professionals belonging to
      various professional categories (physicians, nurses, pharmacy staff, laboratory
      staff, and medical and health workers) and drawn from four hospitals, the study
      explores the relationship between multilingualism and the following: (a)
      patients' rights; (b) staff recruitment, deployment and commitment; (c) human
      asset accounting; (d) physician-population ratio. This language-driven audit
      reveals a number of points, including: ethically questionable practices;
      distributional imbalance in personnel; commendable cases of employee commitment;
      and inequity in renumeration.

PMID- 16808695
TI  - Information empowers but who is empowered?
AB  - This article presents part of the findings of a study that examined an
      information pamphlet written by nurses and given to relatives of patients in a
      Critical Care Unit (CCU) in an Australian acute care hospital. The pamphlet,
      Information for Relatives, was analyzed using Systemic Functional Linguistics
      (SFL) and examines how a relatives' information pamphlet written by nurses
      constructs the reader-relatives' view of a Critical Care Unit. The results
      revealed how the language chosen by the nurse-writers of this pamphlet acts to
      restrict and constrain the reader-relatives while constructing the staff as
      ethical experts. Furthermore, it questions the notion that all information
      empowers healthcare clients and demonstrates how this information pamphlet is not
      value free but has embedded in it social values of the culture from which it
      emanates. The pamphlet empowers the writers and staff, not the relatives.

PMID- 16808696
TI  - 'I didn't think I was at risk': Interdiscursive relations in narratives of sexual
      practices and exposure to HIV.
AB  - This article is concerned with the discursive construction of sexual practices
      and 'risk' in gay men's accounts of exposure to HIV. The data are in-depth
      interviews from two Sydney-based studies. While the events reported in both
      studies were very similar, there are considerable differences in the language
      choices. Drawing on critical discourse analysis and systemic functional
      linguistics, this paper shows how language choices in individual narratives
      resonate intertextually with the public health discourse of safe sex, which
      emphasizes knowledge of safe sex, control over sexual practices and condom use.
      While in accounts of exposure to HIV in the context of prevention sexual practice
      is construed consistently as 'doing' with the speakers as Actor, in accounts of
      exposure to HIV in the context of transmission it is construed predominantly as
      'thinking' and 'being'. There are also differences in the negotiation of
      alternatives. All narratives resonate with the discourse of safe sex, however, it
      is not passively reflected in speech but is actively engaged with and shaped to
      fit the knowledge and understanding of individuals. The narratives also resonate
      with the private world of intimate relationships and everyday life. This suggests
      a notion of 'risk' as a hybrid of multiple, potentially conflicting discourses.

PMID- 16808697
TI  - Reconceptualizing interruptions in physician-patient interviews: cooperative and
      intrusive.
AB  - Results of past research on physician-patient interruption present an
      inconclusive picture. This study reconceptualizes interruption into cooperative
      and intrusive categories. Thirty physician-patient interviews, 13 male/male and
      17 male/female, were audiotaped and microanalyzed. It was found that physicians
      did not interrupt patients more or vice versa. Rather, physicians and patients
      interrupted differently, the former more intrusively and the latter, more
      cooperatively. Furthermore, physicians did not dominate speaking turns nor speak
      more words than patients, as previously believed. We argue that their difference
      may not be measured by the number of words or speaking turns because it is
      embedded in their respective communication style. It was also found that female
      patients exhibited eleven times as much cooperative interruptions as did male
      patients. When physicians interrupted patients, they were unsuccessful only 6% of
      the time. When patients interrupted physicians, they were unsuccessful 32% of the
      time. The results of this study point out the necessity to reconceptualize
      interruptions in physician-patient interviews.

PMID- 16808698
TI  - Presentation of self and symptoms in primary care consultations involving
      patients from non-English speaking backgrounds.
AB  - This paper draws on the PLEDGE research project (Patients with Limited English
      and Doctors in General Practice) 1 The Patients with Limited English and Doctors
      in General Practice (PLEDGE) project was funded by Sir Siegmund Warburg's
      Voluntary Settlement (2001-2003). The research team was: Celia Roberts, Roger
      Jones, Becky Moss, Srikant Sarangi and Val Wass. which has a database of 232
      video-recorded interactions from GP surgeries in South East London. We focus on
      the opening episodes-the first opportunity the patient has to report on why they
      have come to see the doctor-to explore some of the contrasts in self presentation
      and the interactional work that doctors do when faced with the unexpected.
      Patients who speak a local London or standard variety of English present three
      aspects: a description of symptoms, the context in which they occurred, and an
      affective or epistemic stance. These 'micro discourse routines' are accomplished
      interactionally through the design of figure/ground relationships, framing and
      metacommunication and presentation of the 'moral self'. Although some patients
      from non-English speaking backgrounds use broadly similar 'micro discourse
      routines', the majority configure the relationship between medically salient
      facts, adequate contextual information and the stance which conveys the 'moral
      self' in different and apparently less 'orderly' ways. So openings often become
      protracted and harder work interactionally for both sides. While conversation
      analytic studies and communication skills textbooks represent the medical
      consultations as orderly, we suggest that such apparent orderliness must, at
      least, be partly the result of ironing out linguistic and cultural diversity.
      Interactional sociolinguistic analysis is used to shed light on the design of
      these routines and to provide analytic frameworks for doctors in reflecting on
      their own practice in ways which challenge patient-centred models.

PMID- 16808699
TI  - Journalists and jabs: media coverage of the MMR vaccine.
AB  - The MMR vaccine became front-page news in early February 2002, in a much reported
      controversy about alleged links between MMR and autism. We examine both media
      content and public opinion and knowledge to explore how this controversy was
      presented, and, in turn, how this coverage influenced public perceptions. The
      news coverage of MMR was monitored over a seven and a half month period from 28
      January to 15 September, 2002. Two national surveys were conducted-in April and
      in October, 2002-both based on over 1000 face to face interviews, with the
      purpose of exploring what the public learned from the coverage, and how this
      information may have influenced attitudes towards the vaccine. We will argue that
      the media's critical scrutiny of those supporting MMR was not matched by a
      rigorous examination of the case against it, and that the public was, as a
      consequence, often misinformed about the level of risk involved.

PMID- 16808700
TI  - Helping people assess the health risks from lifestyle choices: comparing a
      computer decision aid with customized printed alternative.
AB  - Decisions about lifestyle play a key role in influencing health. Illnesses such
      as heart disease result from combinations of factors, making it hard for people
      to evaluate alternatives (e.g., knowing how much exercise might give similar
      benefit to eating more fruit and vegetables). Computers can provide customized
      risk leaflets and interactive displays, which may encourage people to explore
      potential lifestyle changes by showing the consequences for future health of
      specific combinations of lifestyle changes. This empirical study invited 24 adult
      volunteers to use the information from a customized leaflet or interactive
      display to advise hypothetical patients about lifestyle changes. Advisers used
      both leaflet and computer for different patients, with order counterbalanced
      across volunteers. It was found that more combinations of lifestyle factors were
      explored with the interactive display, especially by the younger volunteers,
      without this taking more time. Most of the older volunteers preferred interacting
      with the computer, and rated it as easier to use than the leaflet. It is
      concluded that easy to use computer interfaces can be devised that help people
      explore the health consequences of personal decisions about lifestyle, and that
      people prefer interactive assistance rather than using printed alternatives.

PMID- 16808701
TI  - Telling the truth about genomics.
AB  - Issues about communication in genomics have moved out of the clinic and into the
      public arena. Scientists other than clinicians are confronted by calls for public
      engagement. Genomics gives rise to these demands partly because it inevitably
      raises the three basic questions of philosophy as outlined by Kant: What can I
      know? What ought I to do? What may I hope? Genomics on its own cannot answer
      these questions. In relation to what can be known, its answer is at best partial.
      Nor can the ought question be settled by science. In fact, science is criticized
      for reducing options while claiming to be neutral in the pursuit of knowledge.
      The answer to the ought question is crucially related to the hope question in so
      far as this deals with issues about the point of human life generally. The role
      of public engagement in relation to all these questions may have different
      objectives. It is argued that there is more of a place for it in relation to the
      hope question than is commonly recognized, and in particular with regard to the
      role of science, which could benefit from developing a service ideal in the sense
      found in discussions of professional ethics.

PMID- 16808704
TI  - Structure and variation in end-of-life discussions in the Surgical Intensive Care
      Unit.
AB  - The research reported here is an exploratory discourse analysis of a corpus of
      six end-of-life discussions in a Surgical Intensive Care Unit (SICU), describing
      the structure and variations of the four phases of an end-of-life discussion in
      terms of the function of each of these phases: the Opening (Phase 1), Description
      of Current Status (Phase 2), Holistic Decision Making (Phase 3), and Logistics of
      Dying (Phase 4). Of particular interest is Phase 2, in which the presentation of
      medical information culminates in an inferential summary statement that functions
      to establish the patient's status as terminal. We argue that it is Phase 2 that
      is crucial in the functional progression of an end-of-life discussion toward a
      decision to move from therapeutic to palliative care, since it is in Phase 2 that
      physicians and families interactionally achieve a consensus that allows a
      decision to withdraw or withhold further treatment, including life support, which
      would be futile and only prolong the patient's suffering. We show how two of the
      end-of-life discussions in the corpus that did not establish the terminal status
      of the patient in Phase 2 did not move to decision making in Phase 3.

PMID- 16808705
TI  - End-of-life decision making is more than rational.
AB  - Most medical models of end-of-life decision making by patients assume a rational
      autonomous adult obtaining and deliberating over information to arrive at some
      conclusion. If the patient is deemed incapable of this, family members are often
      nominated as substitutes, with assumptions that the family are united and
      rational. These are problematic assumptions. We interviewed 23 outpatients with
      cancer about the decision not to resuscitate a patient following cardiopulmonary
      arrest and examined their accounts of decision making using discourse analytical
      techniques. Our analysis suggests that participants access two different
      interpretative repertoires regarding the construct of persons, invoking a
      'modernist' repertoire to assert the appropriateness of someone, a patient or
      family, making a decision, and a 'romanticist' repertoire when identifying either
      a patient or family as ineligible to make the decision. In determining the
      appropriateness of an individual to make decisions, participants informally apply
      'Sanity' and 'Stability' tests, assessing both an inherent ability to reason
      (modernist repertoire) and the presence of emotion (romanticist repertoire) which
      might impact on the decision making process. Failure to pass the tests
      respectively excludes or excuses individuals from decision making. The absence of
      the romanticist repertoire in dominant models of patient decision making has
      ethical implications for policy makers and medical practitioners dealing with
      dying patients and their families.

PMID- 16808706
TI  - 'Things aren't the same, are they?': The management of bad news delivery in the
      discourse of stroke care.
AB  - Health professionals associated with stroke care tend to emphasize the optimistic
      possibilities for recovery from stroke and downplay its disabling nature.
      Therefore, unlike in cancer care, the 'bad news' interview is not a recognized
      part of stroke care. Nevertheless, at some stages in the trajectory of the
      illness the issue of disability may have to be discussed and this paper concerns
      one such occasion. The data are taken from a corpus of video-recorded naturally
      occurring interactions between stroke patients and health professionals. In the
      case studied here, an occupational therapist discusses with a patient the
      arrangements for her care after discharge from hospital. It emerges over the
      course of the interaction that the patient has to face some unpleasant realities
      about her future daily life. By conducting a microanalysis of this interaction,
      using appropriate concepts from conversation analysis and politeness theory, we
      show how the patient and therapist collaboratively manage the emergent 'bad news'
      situation and, over the course of the interaction, arrive at the realization that
      'things are not the same'.

PMID- 16808707
TI  - The interpreter's role with immigrant patients: contrasted points of view.
AB  - Immigration in Western societies sometimes leads to medical consultations without
      any shared language between physician and patient. The intervention of a third
      party is required in such cases. This paper details a study of the role of such a
      third party. Conducted between 1998 and 2001 in French-speaking Switzerland by
      physicians and linguists, this research used several techniques of data
      production. In order to compare the viewpoints of the actors concerned
      (physicians, patients, and translators), researchers used questionnaires, semi
      structured interviews, and focus groups. Analysis of these data reveals that
      professional translators perceive themselves as active participants who improve
      communication by bridging the gap between physician and patient. In the
      translators' perspective, this gap is both linguistic and cultural. On the other
      hand, most physicians and patients interrogated do not share this view. Points of
      view about languages can lead to miscommunication in medical settings in spite of
      a qualified interpreter's presence. This article discusses visions of the
      interpreter's role, which range from instrument to co-therapist.

PMID- 16808708
TI  - Opening stages in triadic medical encounters in Taiwan.
AB  - Opening stages in medical interviews are important because good doctor-patient
      rapport facilitates the doctor's tasks in later stages, especially in triadic
      first-visit interviews where doctors are not acquaintances of patients and
      companions. Given its importance, the research examines opening stages in the
      Taiwanese context from two perspectives: discourse components of opening stages
      and discourse mechanisms of presenting non-acquaintances' identities, especially
      the companions' identities. By examining 30 geriatric triadic encounters
      collected in a teaching hospital in southern Taiwan, this research concludes that
      opening-stage interaction patterns in Taiwanese medical interviews differ from
      Western patterns in the following ways. Under time pressure, Taiwanese doctors
      tend to open the interview in a fast pattern that hardly allows verbal
      participation from the patients. The common practice of presenting non
      acquaintances' identities in Western conversation openings is rarely observed in
      the Taiwanese context. As a result, contrary to the professional norms, most
      companions' identities are not clarified until they talk in the later stages,
      such as the pedigree stage, which is the most natural context for revealing their
      identities. This seeming violation of professional norms, however, can be
      explained by traditional Chinese interaction norms, and can be remedied by
      following another traditional norm-using a situational greeting. Further
      recommendations for Taiwanese medical professionals are also proposed to balance
      these potentially conflicting needs.

PMID- 16808709
TI  - When talking to the patient is difficult: the physician's perspective.
AB  - The aim of the study was to analyze the difficult doctor-patient relationship
      from a doctor's perspective. A qualitative-interpretative approach was employed
      to analyze representations of difficult visits collected by means of written
      narrations. Two main scenarios were identified: (i) a 'personal scenario' in
      which the doctor had difficulties from a purely personal perspective; and (ii) a
      'professional scenario' in which the doctor had difficulties as a professional
      when the 'other' resists or in facing the 'other' who resists. A further scenario
      was identified in which problems were generated by the family of the patient.
      Results suggest that the relation between doctor and patient may be very complex.
      Difficulties may be internal to the doctor, hence intra-psychic, depending on
      being both a professional and a human being. Difficulties may also be external
      between two psychological subjects (labeled as inter-psychic), where interaction
      of the 'you' and the 'other' becomes a battleground, a wall of opposition, or
      alternatively a place of experimentation with relationships. Furthermore,
      external difficulties may also be between more than two persons (labeled as inter
      personal), by the possible multiplicity of the 'other'. This happens in
      particular when the 'other' is represented by the family.

PMID- 16808710
TI  - 'Did you solve it yourself?': Evaluation of self narratives of discrimination by
      people with 'learning difficulties'.
AB  - Narratives about personal experience are shaped by the interactional context, and
      people are required to tell their own stories in a variety of social contexts.
      For people with 'learning difficulties', veracity is a particular and paradoxical
      problem. New policies and strategies require them to take part in public debates,
      while they are traditionally judged to be incompetent to be witnesses to the
      'truth'. Presenting data from an inclusive research project, this paper analyses
      some of the micro strategies by which people with 'learning difficulties' create
      their own research interviews by asking questions, telling stories and evaluating
      their own narratives about discrimination. The interplay of different levels of
      identity in the data and the concept of interactional rights were found to be
      useful analytical tools. By doing research and speaking up for themselves, people
      with 'learning difficulties' can collaborate to take on new situational
      identities; in this context, this paper shows precisely how they evaluate their
      own narratives to focus on various aspects of their own more permanent identity.
      Practical conclusions are drawn, both for people with 'learning difficulties' and
      for their interlocutors, challenging assumptions of blanket incompetence.

PMID- 16808711
TI  - Quality of life to the end.
AB  - Quality of life is a subjective concept, yet there have been some real and
      constructive attempts to measure the quality of a person's life so that
      meaningful comparisons can be made during treatment and as disease progresses. In
      this paper the multifaceted nature of quality of life is explored and the ways
      that the communication of healthcare professionals with a patient can
      dramatically influence the patient's sense of personal dignity and worth.
      Inherent in this are the relationships with the family, particularly with
      children in the family, who may suffer greatly in bereavement. Pressures on
      patients may make them feel a burden, as if they would be better off dead and
      certainly as if others may be better off without them still alive. This sense of
      being a burden is often behind requests for death hastening acts such as
      euthanasia. The fundamental difference between euthanasia and the cessation of
      futile treatments is also explored. The pivotal role of good communication is the
      route to ensuring that issues are addressed, with hope maintained for the patient
      to live as well as possible until they die, and that patients' quality of life is
      maximized.

PMID- 16808712
TI  - The unjust world problem: a rejoinder.

PMID- 16808713
TI  - The unjust world problem: a response to Elliot Mishler.

PMID- 16808715
TI  - Interactional expertise in healthcare encounters.

PMID- 16808716
TI  - Introduction: Professional theories and institutional interaction.

PMID- 16808717
TI  - Communicating for a clinical purpose: strategy in interaction in healthcare
      consultations.
AB  - Many studies of communication employ interviewing techniques and conversation
      analysis, particularly in situations where one participant brings specialist
      resources. Interviews and recorded interactions are usually handled separately:
      ethnographic data are introduced once conversation analysis is complete, to
      validate findings or illustrate their wider significance. However, integrating
      interview data in conversation analysis has the potential to illuminate analysts'
      interpretations, and to enhance professionals' contributions from analysis
      through to dissemination. In this study, interviews highlighted a parameter
      between professionals who actively used communication to manipulate the
      consultation's course, engaging patients at particular points and in particular
      ways, and professionals whose consultation management was more 'clinical' and
      less dependent on interaction. The different ways professionals talked in
      interview were paralleled by differences identified from conversation analysis of
      consultations. For some, 'clinical' orientation was more prevalent in the
      organization of their consultations than 'active' manipulation of communication,
      and their management of the consultation more 'unilateral'. For others,
      communication played a more strategic and integral part in clinical practice, and
      their management of the consultation was more 'bilateral'. These contrasts in
      professionals' descriptions of their consultation management suggest that at
      least some features of a 'bilateral' approach are consciously employed and may be
      teachable.

PMID- 16808718
TI  - Comparing homeopathic and general practice consultations: the case of problem
      presentation.
AB  - Both general practice and homeopathic consultations are organized around the key
      task of treating patients' health-related problems. Despite their different
      theories of healing, interactions between professionals and patients in both
      share many features, though there are also clear differences in the ways in which
      patients and professionals go about the process of problem solving. This paper
      compares the ways in which a specific activity, the delivery and reception of the
      reason for the visit, is managed in these two institutional environments. Through
      the comparison, it discusses ways in which participants are informed by the
      different theories of healing and 'ideal' models of interaction in their
      activities at the consultation, and points at some discrepancies between theories
      on treatment and theories on interaction. Furthermore, the paper shows how other
      contextual features, such as the institutionalized structure of a service
      encounter, may be consequential for the interaction analyzed. Finally, the paper
      discusses the potential benefits of this analysis to the practices studied.

PMID- 16808719
TI  - Discussing patients' drinking and eating habits in medical and homeopathic
      consultations.
AB  - We explore the variety of practices professionals and patients use whilst
      discussing patients' eating and drinking habits in general practice and in
      homeopathic consultations. Our aim is to show how the interaction is shaped, on
      the one hand, by the professionals' theories and goals and, on the other hand, by
      the participants' orientations to other contextual features. In these two fields
      of medicine the discussions on the patients' lifestyle have a different role in
      the healing process: in general practice, drinking is considered a possible
      health risk, but in homeopathy, information concerning patients' eating and
      drinking habits is needed for defining the patients' idiosyncratic
      characteristics. This difference is indicated in the ways in which the
      professionals deliver their questions about patients' lifestyles and in the ways
      in which the patients design their responses and the discussion develops.
      However, the practices used by the participants also reflect their orientation to
      the institution-related tasks, such as maintaining professional neutrality and
      being a good patient, as well as to the wider cultural norms and discourses
      concerning socially appropriate behavior outside the institution. We also discuss
      the extent to which these different orientations are consistent or inconsistent
      with the professionals' theories and goals.

PMID- 16808720
TI  - Official recommendations and actual practice in physiotherapy: managing troubles
      of physical performance.
AB  - This paper explores relations between official written recommendations for
      physiotherapists and actual practice. It does so by presenting and discussing
      findings from a conversation analytic study of 74 physiotherapy treatment
      sessions video-recorded in four English hospitals. Various practices are
      described by which therapists address troubles of ongoing or recent physical
      performance by patients during phases of sessions that are occupied with
      therapists' instructions in treatment activities and patients' physical
      responses. Divergence between practice and official guidance can be observed,
      particularly regarding recommendations that therapists always be unambiguous and
      clear in their communication with patients. Also, there seem to be conflicting
      demands between maintaining performance of physical treatment activities, whilst
      also spending time giving patients information and explanation about troubles of
      performance, and checking their understanding (as is recommended). There are also
      conflicting demands between individual recommendations. These observations inform
      a discussion of the wider challenges involved in formulating relevant,
      appropriate official guidance on communication practice. I argue that the
      difficulties of auditing actual conduct against official recommendations on
      interaction should be acknowledged, and that recommendations should be explicitly
      tentative and broad. Conversation analytic studies can provide resources and
      understandings to complement and augment such official guidance.

PMID- 16808721
TI  - Patients' responses to interpretations: a dialogue between conversation analysis
      and psychoanalytic theory.
AB  - The paper reports a conversation analytical study of patients' responses to
      interpretations in psychoanalysis. The data come from 27 tape-recorded and
      transcribed psychoanalytic sessions involving three analyst-patient dyads. The
      study seeks to facilitate dialogue between conversation analytical (CA) findings
      and psychoanalytic theory by using CA to describe the practices in and through
      which the psychoanalytic theory concerning interpretation is realized in actual
      interactions. Four empirical observations are reported in the paper: (1) The
      analysts actively pursue a more than minimal response from the patient to their
      interpretations. (2) A typical extended response to an interpretation involves an
      elaboration, which is an utterance in which the patient takes up some aspect of
      the interpretation and continues discussion on that. (3) Even though elaborations
      convey agreement with the interpretation, they often also involve different
      degrees of discontinuity with what the interpretation initially aimed at. (4)
      This discontinuity is sometimes facilitated by the analyst's own actions. These
      observations invite some specifications in the picture of interpretations
      provided by psychoanalytic theory.

PMID- 16808722
TI  - 'Let the heart speak out'--interviewing practices by psychiatrists from two
      different traditions.
AB  - In the present article, we investigate the extent to which professional theories
      that underlie, inform, and guide the interviewing practices of two psychiatrists
      (a neuropsychiatrist and a psychoanalyst) are discursively displayed in their
      ways of conducting a psychiatric interview. This study analyses excerpts from two
      audio-recorded psychiatric interviews held at the Institute of Psychiatry of the
      Federal University of Rio de Janeiro. It follows theoretical and methodological
      frameworks derived from interactional sociolinguistics. Ethnographic data and
      research interviews with both clinicians also ground our discussion. Using frame
      analysis as a central tool, we found that the psychiatrist who subscribes to a
      neuropsychiatric orientation displays a concern on assessing the patient's
      cognitive processes, and shifts topics away from the patient's delusions to
      (re)introduce the institutional frame of the psychiatric interview. By contrast,
      the psychiatrist who holds a psychoanalytic orientation towards interviewing not
      only listens attentively to very personal topics introduced by the patient, but
      also sustains and develops these topics. Most of all, she proposes and stays
      within conversational frames. In keeping a dual understanding about their
      practices in the interview situation, both doctors balance the need to follow the
      institutional agenda and the need to listen to the patient, despite their
      different theoretical orientations.

PMID- 16808723
TI  - Commentary 1: Professional theories and institutional interaction.

PMID- 16808724
TI  - Commentary 2: Professional theories and institutional interaction.

PMID- 16808725
TI  - The unjust world problem revisited: what should health providers and researchers
      care about?

PMID- 16808727
TI  - Differential effects of psychoactive drugs in adolescents and adults.
AB  - It is well known that most people who use psychoactive drugs started as
      teenagers. In spite of this, there has been little preclinical research on the
      effects of psychostimulants during adolescence. Recently, however, a number of
      laboratories have begun to focus on drug effects in adolescents as compared with
      adults. The data show that there are unique responses to drugs during this period
      of development. This review will focus on our current understanding of
      neurochemical and behavioral drug effects during adolescence.

PMID- 16808728
TI  - Cortical mechanisms of cocaine sensitization.
AB  - Behavioral sensitization is the augmented motor-stimulant response that occurs
      with repeated, intermittent exposure to most drugs of abuse, including cocaine.
      Sensitization, which is a long-lasting phenomenon, is thought to underlie drug
      craving and relapse to drug use. Much research has been conducted to determine
      the neural mechanisms of sensitization. The bulk of this effort has focused on
      the nucleus accumbens and ventral tegmental area (VTA) that comprise a portion of
      the mesolimbic dopamine system. Recently, studies have begun to also explore the
      role of the medial prefrontal cortex (mPFC) in sensitization, in part because
      this region provides glutamatergic innervation to the VTA and nucleus accumbens.
      The present review will coalesce these studies into a working hypothesis that
      states that cocaine sensitization results from a decrease in inhibitory
      modulation of excitatory transmission from the mPFC to the VTA and nucleus
      accumbens. The discussion will revolve around how repeated cocaine exposure
      alters dopamine, gamma-aminobutyric acid (GABA), and glutamate regulation of
      pyramidal cell activity. It will be proposed that cocaine-induced alterations in
      cortical transmission occur in two phases. During early withdrawal from repeated
      cocaine exposure, changes in neurotransmitter release are thought to underlie the
      decreased inhibitory modulation of pyramidal projection neurons. Following more
      prolonged withdrawal, the attenuation in inhibitory transmission appears to occur
      at the receptor level. A model will be presented that may serve to direct future
      studies on the involvement of the mPFC in the development of cocaine
      sensitization, which ultimately could lead to development of pharmacotherapies
      for cocaine addiction.

PMID- 16808729
TI  - Amphetamine neurotoxicity: cause and consequence of oxidative stress.
AB  - Oxidative stress has been demonstrated to occur in response to high doses of
      substituted amphetamines such as methamphetamine (METH) and 3,4-methlyene
      dioxymethamphetamine (MDMA). This term represents a set of complex and multi
      faceted precursor events that occur in both a parallel and serial manner,
      eventually converging to produce oxidative damage. This critical review goes
      beyond the compilation of previously well-documented evidence demonstrating that
      oxidative stress mediates METH and MDMA toxicity to dopamine and/or serotonin
      nerve terminals. The diverse causes, effects, and impact of pro-oxidative
      processes produced by these drugs are highlighted, integrated, and assembled into
      a proposed temporal sequence in an effort to explain the long-term neurochemical
      changes produced by amphetamines. Multiple factors are considered, including
      dopamine, glutamate, impaired mitochondrial bioenergetics, and inflammatory
      processes, all of which converge and are necessary but alone may be insufficient
      to cause damage to dopamine and/or 5-HT terminals. In addition, the processes
      linking inflammation and oxidative stress are considered and described as a
      feedforward process. The self-perpetuating cycle of inflammation and oxidative
      stress that is initiated by dopamine, glutamate, and mitochondrial dysfunction
      may extend well beyond the acute pharmacodynamic effects of the drugs and could
      represent an underlying and potentially progressive degenerative process.

PMID- 16808730
TI  - Plumbism or lead intoxication mimicking an abdominal tumor.
AB  - The clinical presentation of lead intoxication may vary widely and in the absence
      of a high clinical index of suspicion, the diagnosis may be missed. The effects
      of lead on mitochondrial oxidative phosphorylation and its interaction with
      calcium-mediated processes explain the heterogenous presentation. In this case
      report, the diagnosis was finally made when bilateral wrist drop developed on top
      of abdominal cramps and anemia. Before, ascites raised the suspicion of a tumor.
      Therefore, each element of the triad of unexplained anemia, abdominal cramps, and
      bilateral wrist (or foot) drop should lead any physician to consider the
      diagnosis of lead intoxication. This case also illustrates the importance of a
      careful and meticulous social history in patient management.

PMID- 16808731
TI  - Iodine-induced thyrotoxicosis after ingestion of kelp-containing tea.
AB  - Complementary medication is en vogue and an increasing number of patients consume
      herbal medicine without reporting their use to physicians. We report a case of
      iodine-induced hyperthyroidism due to the ingestion of a kelp-containing tea. A
      39-year-old woman with multinodular goiter presented with typical signs of
      hyperthyroidism, which was confirmed by endocrine tests. She was not exposed to
      iodinated radiocontrast media and did not take medications containing iodine,
      such as amiodarone. However, a detailed medical history revealed that she had
      been treated for a period of 4 weeks by a Chinese alternative practitioner with a
      herbal tea containing kelp because of her enlarged thyroid. The consumption of
      the tea was discontinued and an antithyroid drug therapy was initiated.
      Physicians should advise patients with underlying thyroid disease to avoid all
      complementary or alternative medications containing iodine.

PMID- 16808732
TI  - Dysphonia as first symptom of late-onset myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction
      that causes muscle weakness and fatigue. Fluctuating fatigue of skeletal muscles
      is the key clinical feature. Late-onset MG is more frequent in elderly men and is
      often misdiagnosed. While involvement of oropharyngeal musculature has been
      described with symptoms of dysphagia and slurred speech, the presence of
      fluctuating dysphonia as the first symptom of late-onset MG has not been
      emphasized. The case of an elderly man, who demonstrated voice changes and later
      swallowing impairment with weight loss, is reported. This case presentation of
      late-onset MG emphasizes that this form of the disease should be considered in
      the differential diagnosis of acute onset dysphonia in elderly persons.

PMID- 16808733
TI  - Chest pain in a young basketball player.
AB  - A 32-year-old man was elbowed in the chest while fighting for a rebound in a
      recreational basketball game. He fell to the ground and his chest ached from the
      blow. Four days later he developed more severe chest pressure with dyspnea and
      came to the hospital. His chest wall was tender and his pulse slow, but the
      remainder of his physical examination was normal. Electrocardiogram showed sinus
      bradycardia, first-degree atrioventricular (AV) block, and occasional isorhythmic
      AV dissociation, but no ischemic ST-T changes. Cardiac troponin I rose to 1.74
      ng/mL (normal <0.50). The patient therefore underwent coronary angiography,
      showing spiral dissection of the right coronary artery with extensive thrombus
      filling the distal portion of the vessel. Stenting was unsuccessful in restoring
      flow. This case highlights the potential dangers of blunt chest trauma in
      recreational sports and shows how angiography can distinguish myocardial
      contusion from coronary artery dissection.

PMID- 16808734
TI  - Using the Patient Health Questionnaire-9 to measure depression among racially and
      ethnically diverse primary care patients.
AB  - OBJECTIVE: The Patient Health Questionnaire depression scale (PHQ-9) is a well
      validated, Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition
      (DSM-IV) criterion-based measure for diagnosing depression, assessing severity
      and monitoring treatment response. The performance of most depression scales
      including the PHQ-9, however, has not been rigorously evaluated in different
      racial/ethnic populations. Therefore, we compared the factor structure of the PHQ
      9 between different racial/ethnic groups as well as the rates of endorsement and
      differential item functioning (DIF) of the 9 items of the PHQ-9. The presence of
      DIF would indicate that responses to an individual item differ significantly
      between groups, controlling for the level of depression. MEASUREMENTS: A combined
      dataset from 2 separate studies of 5,053 primary care patients including non
      Hispanic white (n=2,520), African American (n=598), Chinese American (n=941), and
      Latino (n=974) patients was used for our analysis. Exploratory principal
      components factor analysis was used to derive the factor structure of the PHQ-9
      in each of the 4 racial/ethnic groups. A generalized Mantel-Haenszel statistic
      was used to test for DIF. RESULTS: One main factor that included all PHQ-9 items
      was found in each racial/ethnic group with alpha coefficients ranging from 0.79
      to 0.89. Although endorsement rates of individual items were generally similar
      among the 4 groups, evidence of DIF was found for some items. CONCLUSIONS: Our
      analyses indicate that in African American, Chinese American, Latino, and non
      Hispanic white patient groups the PHQ-9 measures a common concept of depression
      and can be effective for the detection and monitoring of depression in these
      diverse populations.

PMID- 16808735
TI  - Perceived discrimination and use of preventive health services.
AB  - BACKGROUND: Little is known about the relation between perceptions of health care
      discrimination and use of health services. OBJECTIVES: To determine the
      prevalence of perceived discrimination in health care, its association with use
      of preventive services, and the contribution of perceived discrimination to
      disparities in these services by race/ethnicity, gender, and insurance status.
      DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 54,968 respondents to
      the 2001 California Health Interview Survey. MEASUREMENTS: Subjects were asked
      about experience with discrimination in receiving health care and use of 6
      preventive health services, all within the previous 12 months. METHODS: We used
      multivariate logistic regression with propensity-score methods to examine the
      adjusted relationship between perceived discrimination and receipt of preventive
      care. RESULTS: Discrimination was reported by 4.7% of respondents, and among
      these respondents the most commonly reported reasons were related to type of
      insurance (27.6%), race or ethnicity (13.7%), and income (6.7%). In adjusted
      analyses, persons who reported discrimination were less likely to receive 4
      preventive services (cholesterol testing for cardiovascular disease, hemoglobin
      A1c testing and eye exams for diabetes, and flu shots), but not 2 other services
      (aspirin for cardiovascular disease, prostate specific antigen testing).
      Adjusting for perceived discrimination did not significantly change the relative
      likelihood of receipt of preventive care by race/ethnicity, gender, and insurance
      status. CONCLUSIONS: Persons who report discrimination may be less likely to
      receive some preventive health services. However, perceived discrimination is
      unlikely to account for a large portion of observed disparities in receipt of
      preventive care.

PMID- 16808736
TI  - Racial differences in attitudes toward innovative medical technology.
AB  - BACKGROUND: New medical technologies are used at different rates among whites and
      blacks. This variation may be partially explained by racial differences in
      patient innovativeness-the propensity of patients to adopt unfamiliar therapies.
      OBJECTIVE: To measure how innovativeness varies among patients and how it may
      influence patients' attitudes toward new medical technologies. DESIGN: Cross
      sectional survey. PARTICIPANTS: Primary care patients (n=171-108 blacks, 63
      whites) at an urban Veterans Affairs medical center. MEASUREMENTS: Respondents
      answered questions about their general innovativeness and innovativeness
      regarding medical technology, and they responded to a vignette describing either
      a hypothetical new prescription drug or implantable device. RESULTS: There were
      no significant racial differences in general innovativeness, but whites had
      higher medical technology innovativeness (P=.001). Whites were also more likely
      to accept the new prescription drug (P=.003), but did not differ from blacks in
      acceptance of the new implantable device. In multivariate analyses, lower medical
      technology innovativeness scores among blacks were significantly associated with
      less favorable reactions to both the prescription drug (P<.001) and the medical
      device (P<.001). In contrast, although whites with lower medical technology
      innovativeness were similarly less inclined to accept the new implantable device
      (P=.02), there was no significant association between medical technology
      innovativeness and positive attitudes to the new prescription drug among whites.
      CONCLUSIONS: Blacks and whites have differing attitudes toward medical
      innovation. These differences are associated with significant racial differences
      in response to particular health care technologies. These findings suggest
      potentially remediable causes for racial differences in the utilization of
      innovative medical technologies.

PMID- 16808737
TI  - Personal growth during internship: a qualitative analysis of interns' responses
      to key questions.
AB  - BACKGROUND: During clinical training, house officers frequently encounter intense
      experiences that may affect their personal growth. The purpose of this study was
      to explore processes related to personal growth during internship. DESIGN:
      Prospective qualitative study conducted over the course of internship.
      PARTICIPANTS: Thirty-two postgraduate year (PGY)-1 residents from 9 U.S. internal
      medicine training programs. APPROACH: Every 8 weeks, interns responded by e-mail
      to an open-ended question related to personal growth. Content analysis methods
      were used to analyze the interns' writings to identify triggers, facilitators,
      and barriers related to personal growth. RESULTS: Triggers for personal growth
      included caring for critically ill or dying patients, receiving feedback,
      witnessing unprofessional behavior, experiencing personal problems, and dealing
      with the increased responsibility of internship. Facilitators of personal growth
      included supportive relationships, reflection, and commitment to core values.
      Fatigue, lack of personal time, and overwhelming work were barriers to personal
      growth. The balance between facilitators and barriers may dictate the extent to
      which personal growth occurs. CONCLUSIONS: Efforts to support personal growth
      during residency training include fostering supportive relationships, encouraging
      reflection, and recognizing interns' core values especially in association with
      powerful triggers.

PMID- 16808738
TI  - Managing acutely ill substance-abusing patients in an integrated day hospital
      outpatient program: medical therapies, complications, and overall treatment
      outcomes.
AB  - BACKGROUND: Substance-abusing adults are admitted to hospitals for medical
      complications from their drug and alcohol use at substantially higher rates than
      the general public; yet, their care is often defined by against medical advice
      (AMA) discharges and low rates of referral to addiction treatment programs.
      METHODS: We present findings from a chart review of consecutive admissions to an
      integrated medical-substance abuse treatment program designed for acutely ill,
      hospitalized substance using adults. We specifically looked at factors associated
      with program completion and medical complications in this cohort of at-risk
      adults. RESULTS: Overall, 83 patient cases were studied. The mean age was 41.2
      years; most were African American (73.5%), male (68.7%), and homeless (77.1%).
      Heroin (96.4%) and cocaine (88.0%), followed by alcohol (44.6%) were the most
      commonly used substances before admission. The most common admitting diagnoses
      were infectious endocarditis (43.4%), abscess or nonhealing ulcer (18.1%), and
      osteomyelitis (13.3%) with intravenous antibiotic (68.7%), physical therapy
      (48.2%), or wound care (41.0%), the most commonly prescribed care on the
      integrated care/day hospital unit. The mean length of stay in the day hospital
      was 12.4 days. Overall, 69.9% of patients successfully completed their medical
      therapy, and 63.9% were successfully referred to an outpatient substance abuse
      treatment program. Only 10.8% required an unscheduled hospital readmission and
      15.7% required an after-hours emergency department visit during their stay.
      CONCLUSION: Outpatient/day hospital-based integrated treatment is a viable option
      for medically ill substance-abusing adults who would otherwise be hospitalized
      and is associated with higher than expected completion rates and low rate of
      complications. Co-locating the unit at a hospital and integrating extensive
      social supports appear to be key components to this model.

PMID- 16808739
TI  - How do providers assess antihypertensive medication adherence in medical
      encounters?
AB  - BACKGROUND: Poor adherence to antihypertensives has been shown to be a
      significant factor in poor blood pressure (BP) control. Providers' communication
      with patients about their medication-taking behavior may be central to improving
      adherence. OBJECTIVE: The goal of this study was to characterize the ways in
      which providers ask patients about medication taking. DESIGN: Clinical encounters
      between primary care providers and hypertensive patients were audiotaped at 3
      Department of Veterans' Affairs medical centers. PARTICIPANTS: Primary care
      providers (n=9) and African-American and Caucasian patients (n=38) who were
      diagnosed with hypertension (HTN). APPROACH: Transcribed audiotapes of clinical
      encounters were coded by 2 investigators using qualitative analysis based on
      sociolinguistic techniques to identify ways of asking about medication taking.
      Electronic medical records were reviewed after the visit to determine the BP
      measurement for the day of the taped encounter. RESULTS: Four different aspects
      of asking about medication were identified: structure, temporality, style and
      content. Open-ended questions generated the most discussion, while closed-ended
      declarative statements led to the least discussion. Collaborative style and use
      of lay language were also seen to facilitate discussions. In 39% of encounters,
      providers did not ask about medication taking. Among patients with uncontrolled
      HTN, providers did not ask about medications 33% of the time. CONCLUSION:
      Providers often do not ask about medication-taking behavior, and may not use the
      most effective communication strategies when they do. Focusing on the ways in
      which providers ask about patients' adherence to medications may improve BP
      control.

PMID- 16808740
TI  - What drives referral from primary care physicians to mental health specialists? A
      randomized trial using actors portraying depressive symptoms.
AB  - BACKGROUND: Referral from primary care to the mental health specialty sector is
      important but poorly understood. OBJECTIVE: Identify physician characteristics
      influencing mental health referral. DESIGN: Randomized controlled trial using
      Standardized Patients (SPs). SETTING: Offices of primary care physicians in 3
      cities. PARTICIPANTS: One hundred fifty-two family physicians and general
      internists recruited from 4 broad practice settings; 18 middle aged Caucasian
      female actors. INTERVENTION: Two hundred and ninety-eight unannounced SP visits,
      with assignments constrained so physicians saw 1 SP with major depression and 1
      with adjustment disorder. MEASUREMENTS: Mental health referrals via SP written
      reports; physician and system characteristics through a self-administered
      physician questionnaire. RESULTS: Among 298 SP visits, 107 (36%) resulted in
      mental health referral. Referrals were less likely among physicians with greater
      self-confidence in their ability to manage antidepressant therapy (adjusted odds
      ratio [AOR] 0.39, 95% confidence interval [CI] 0.17 to 0.86) and were more likely
      if physicians typically spent > or =10% of professional time on nonclinical
      activities (AOR 3.42, 95% CI 1.45 to 8.07), had personal life experience with
      psychotherapy for depression (AOR 2.74, 95% CI 1.15 to 6.52), or usually had
      access to mental health consultation within 2 weeks (AOR 2.94, 95% CI 1.26 to
      6.92). LIMITATION: The roles portrayed by SPs may not reflect the experience of a
      typical panel of primary care patients. CONCLUSIONS: Controlling for patient and
      health system factors, physicians' therapeutic confidence and personal experience
      were important influences on mental health referral. Research is needed to
      determine if addressing these factors can facilitate more appropriate care.

PMID- 16808741
TI  - Predictors of quitting among African American light smokers enrolled in a
      randomized, placebo-controlled trial.
AB  - OBJECTIVE: To examine the predictors of quitting among African American (AA)
      light smokers (<10 cigarettes per day) enrolled in a smoking cessation trial.
      METHODS: Baseline variables were analyzed as potential predictors from a 2 x 2
      cessation trial in which participants were randomly assigned to 1 of 4 treatment
      groups: nicotine gum plus health education (HE) counseling, nicotine gum plus
      motivational interviewing (MI) counseling, placebo gum plus HE counseling, or
      placebo gum plus MI counseling. Chi-square tests, 2 sample t-tests, and multiple
      logistic regression analyses were used to identify predictors of cotinine (COT)
      verified abstinence at month 6. RESULTS: In the final regression model, HE rather
      than MI counseling (odds ratio [OR]=2.26%, 95% confidence interval [CI]=1.36 to
      3.74), older age (OR=1.03%, 95% CI=1.01 to 1.06), and higher body mass index
      (OR=1.04%, 95% CI=1.01 to 1.07) significantly increased the likelihood of
      quitting, while female gender (OR=0.46%, 95% CI=0.28 to 0.76),</=$1,800/month
      income (OR=0.60%, 95% CI=0.37 to 0.97), higher baseline COT (OR=0.948%, 95%
      CI=0.946 to 0.950), and not completing all counseling sessions (OR=0.48%, 95%
      CI=0.27 to 0.84) reduced the odds of quitting. CONCLUSIONS: Individual
      characteristics may decrease the likelihood of quitting; however, the provision
      of directive, advice-oriented counseling focused on the addictive nature of
      nicotine, health consequences of smoking, benefits of quitting, and development
      of a concrete quit plan may be an important and effective facilitator of quitting
      among AA light smokers.

PMID- 16808742
TI  - Lack of adherence with preoperative B-blocker recommendations in a multicenter
      study.
AB  - BACKGROUND: Clinical guidelines support the use of preoperative B-blocker in
      select patients. Patient safety groups have sought to measure the level of
      adherence to these recommendations. OBJECTIVE: This study was performed to
      compare the utilization of preoperative B-blocker with current guidelines across
      multiple diverse institutions. DESIGN: Retrospective chart review was performed
      of inpatients undergoing noncardiac surgery across 5 hospital centers during 2003
      to 2004. The primary outcome of interest was the administration of preoperative B
      blocker. PARTICIPANTS: The study sample included 1,304 randomly selected patients
      meeting the guideline criteria for preoperative B-blockade. MEASUREMENTS AND MAIN
      RESULTS: Among patients meeting recommendations for preoperative B-blocker, only
      44% (430/983) received B-blocker before surgery. Patients who had not previously
      received B-blocker were given B-blocker before surgery in only 14% (85/600) of
      cases. Target heart rates goals for perioperative B-blockade were achieved in 26%
      (113/430) of cases. Predictors for initiating preoperative B-blocker included
      nonelective surgery or a history of hypertension or diabetes. Individual
      hospitals were independently predictive of preoperative B-blocker administration
      in multivariable models. CONCLUSIONS: Preoperative B-blocker was significantly
      underutilized when compared with the current guideline recommendations. Target
      heart rate goals were not achieved in clinical practice, and few hospitalized
      patients had preoperative B-blockade initiated. The lack of adherence to
      preoperative B-blocker recommendations in practice may be impacted by ongoing
      clinical questions regarding the appropriate selection of candidates for this
      therapy. Further efforts toward achieving guideline recommendations for
      preoperative B-blocker use should be focused on the subset of patients that are
      uniformly agreed upon to be at high risk for cardiac events.

PMID- 16808743
TI  - Influence of orthostatic hypotension on mortality among patients discharged from
      an acute geriatric ward.
AB  - BACKGROUND: Orthostatic hypotension (OH) is a common finding among older
      patients. The impact of OH on mortality is unknown. OBJECTIVE: To study the long
      term effect of OH on total and cardiovascular mortality. PATIENTS AND METHODS: A
      total of 471 inpatients (227 males and 244 females), with a mean age of 81.5
      years who were hospitalized in an acute geriatric ward between the years 1999 and
      2000 were included in the study. Orthostatic tests were performed 3 times during
      the day on all patients near the time of discharge. Orthostatic hypotension was
      defined as a fall of at least 20 mmHg in systolic blood pressure (BP) and/or 10
      mmHg in diastolic BP upon assuming an upright posture at least twice during the
      day. Patients were followed until August 31, 2004. Mortality data were taken from
      death certificates. RESULTS: One hundred and sixty-one patients (34.2%)
      experienced OH at least twice. Orthostatic hypotension had no effect on all cause
      and cause specific mortality. Over a follow-up of 3.47+/-1.87 years 249 patients
      (52.8%) had died 83 of whom (33.3%) had OH. Age-adjusted mortality rates in those
      with and without OH were 13.4 and 15.7 per 100 person-years, respectively. Cox
      proportional hazards model analysis demonstrated that male gender, age, diabetes
      mellitus, and congestive heart failure increased and high body mass index
      decreased total mortality. CONCLUSIONS: Orthostatic hypotension is relatively
      common in elderly patients discharged from acute geriatric wards, but has no
      impact on vascular and nonvascular mortality.

PMID- 16808744
TI  - Measuring pain as the 5th vital sign does not improve quality of pain management.
AB  - BACKGROUND: To improve pain management, the Veterans Health Administration
      launched the "Pain as the 5th Vital Sign" initiative in 1999, requiring a pain
      intensity rating (0 to 10) at all clinical encounters. OBJECTIVE: To measure the
      initiative's impact on the quality of pain management. DESIGN: We retrospectively
      reviewed medical records at a single medical center to compare providers' pain
      management before and after implementing the initiative and performed a subgroup
      analysis of patients reporting substantial pain (> or =4) during a
      postimplementation visit. PARTICIPANTS: Unique patient visits selected from all
      15 primary care providers of a general medicine outpatient clinic. MEASUREMENTS:
      We used 7 process indicators of quality pain management, based on appropriately
      evaluating and treating pain, to assess 300 randomly selected visits before and
      300 visits after implementing the pain initiative. RESULTS: The quality of pain
      care was unchanged between visits before and after the pain initiative (P>.05 for
      all comparisons): subjective provider assessment (49.3% before, 48.7% after),
      pain exam (26.3%, 26.0%), orders to assess pain (11.7%, 8.3%), new analgesic
      (8.7%, 11.0%), change in existing analgesics (6.7%, 4.3%), other pain treatment
      (11.7%, 13.7%), or follow-up plans (10.0%, 8.7%). Patients (n=79) who reported
      substantial pain often did not receive recommended care: 22% had no attention to
      pain documented in the medical record, 27% had no further assessment documented,
      and 52% received no new therapy for pain at that visit. CONCLUSIONS: Routinely
      measuring pain by the 5th vital sign did not increase the quality of pain
      management. Patients with substantial pain documented by the 5th vital sign often
      had inadequate pain management.

PMID- 16808745
TI  - Is there a race-based disparity in the survival of veterans with HIV?
AB  - BACKGROUND: Disparities in survival for black patients with HIV in the United
      States have been reported. The VA is an equal access health care system.
      OBJECTIVE: To determine whether such disparities are present in the VA health
      care system. DESIGN: Retrospective cohort study using national VA administrative
      databases. PATIENTS: Two thousand three hundred and four white and 3,641 black
      HIV-infected patients first hospitalized for HIV between October 1, 1996 and
      September 30, 2000. MEASUREMENTS: Thirty-day mortality after first
      hospitalization with HIV, and subsequent long-term survival. Follow-up ended at
      death or September 30, 2002. Data were adjusted for age, sex, HIV disease
      severity, non-HIV-related comorbidities, primary discharge diagnosis, hepatitis C
      status, and facility effects. RESULTS: The mean follow-up was 3.2 years. Overall
      survival was similar for black patients compared with white patients (adjusted
      hazard ratio 1.09, P=.09). Hospital mortality was 7.0% for black and 6.4% for
      white patients (P=.35). Adjusted hospital mortality for black patients was
      similar to that of white patients (odds ratio 1.20, P=.10). Long-term survival
      after hospitalization did not significantly differ by race (adjusted hazard ratio
      1.07, P=.21, for black patients compared with white patients). CONCLUSIONS:
      Survival during and after first hospitalization with HIV in the VA did not
      significantly differ for white and black patients, possibly indicating similar
      effectiveness of care for HIV. Further research is needed to understand the
      reasons for the lack of disparities for VA patients with HIV and whether the VA's
      results could be replicated.

PMID- 16808746
TI  - A matter of perspective: choosing for others differs from choosing for yourself
      in making treatment decisions.
AB  - BACKGROUND: Many people display omission bias in medical decision making,
      accepting the risk of passive nonintervention rather than actively choosing
      interventions (such as vaccinations) that result in lower levels of risk.
      OBJECTIVE: Testing whether people's preferences for active interventions would
      increase when deciding for others versus for themselves. RESEARCH DESIGN: Survey
      participants imagined themselves in 1 of 4 roles: patient, physician treating a
      single patient, medical director creating treatment guidelines, or parent
      deciding for a child. All read 2 short scenarios about vaccinations for a deadly
      flu and treatments for a slow-growing cancer. PARTICIPANTS: Two thousand three
      hundred and ninety-nine people drawn from a demographically stratified internet
      sample. MEASURES: Chosen or recommended treatments. We also measured
      participants' emotional response to our task. RESULTS: Preferences for risk
      reducing active treatments were significantly stronger for participants imagining
      themselves as medical professionals than for those imagining themselves as
      patients (vaccination: 73% [physician] & 63% [medical director] vs 48% [patient],
      Ps<.001; chemotherapy: 68% & 68% vs 60%, Ps<.012). Similar results were observed
      for the parental role (vaccination: 57% vs 48%, P=.003; chemotherapy: 72% vs 60%,
      P<.001). Reported emotional reactions were stronger in the responsible medical
      professional and parental roles yet were also independently associated with
      treatment choice, with higher scores associated with reduced omission tendencies
      (OR=1.15 for both regressions, Ps<.01). CONCLUSIONS: Treatment preferences may be
      substantially influenced by a decision-making role. As certain roles appear to
      reinforce "big picture" thinking about difficult risk tradeoffs, physicians and
      patients should consider re-framing treatment decisions to gain new, and
      hopefully beneficial, perspectives.

PMID- 16808747
TI  - Patterns of communication through interpreters: a detailed sociolinguistic
      analysis.
AB  - BACKGROUND: Numerous articles have detailed how the presence of an interpreter
      leads to less satisfactory communication with physicians; few have studied how
      actual communication takes place through an interpreter in a clinical setting.
      OBJECTIVE: Record and analyze physician-interpreter-patient interactions. DESIGN:
      Primary care physicians with high-volume Hispanic practices were recruited for a
      communication study. Dyslipidemic Hispanic patients, either monolingual Spanish
      or bilingual Spanish-English, were recruited on the day of a normally scheduled
      appointment and, once consented, recorded without a researcher present in the
      room. Separate postvisit interviews were conducted with the patient and the
      physician. All interactions were fully transcribed and analyzed. PARTICIPANTS:
      Sixteen patients were recorded interacting with 9 physicians. Thirteen patients
      used an interpreter with 8 physicians, and 3 patients spoke Spanish with the 1
      bilingual physician. APPROACH: Transcript analysis based on sociolinguistic and
      discourse analytic techniques, including but not limited to time speaking,
      analysis of questions asked and answered, and the loss of semantic information.
      RESULTS: Speech was significantly reduced and revised by the interpreter,
      resulting in an alteration of linguistic features such as content, meaning,
      reinforcement/validation, repetition, and affect. In addition, visits that
      included an interpreter had virtually no rapport-building "small talk," which
      typically enables the physician to gain comprehensive patient history, learn
      clinically relevant information, and increase emotional engagement in treatment.
      CONCLUSIONS: The presence of an interpreter increases the difficulty of achieving
      good physician-patient communication. Physicians and interpreters should be
      trained in the process of communication and interpretation, to minimize
      conversational loss and maximize the information and relational exchange with
      interpreted patients.

PMID- 16808748
TI  - Osteoporosis risk assessment and ethnicity: validation and comparison of 2
      clinical risk stratification instruments.
AB  - BACKGROUND: Dual energy x-ray absorptiometry (DXA), coupled with early treatment,
      may reduce morbidity and mortality associated with osteoporosis. Clinical tools
      to enhance selection of women for DXA screening have not been developed or
      validated in an ethnically diverse population. OBJECTIVE: To compare the
      performance of the osteoporosis risk assessment instrument (ORAI) and the simple
      calculated osteoporosis risk estimation (SCORE) instrument across 3 racial/ethnic
      groups to identify women who would benefit from DXA scans. DESIGN: Blinded
      comparison of the instruments in a cross-sectional sample. PARTICIPANTS: Two
      hundred twenty-six postmenopausal women were recruited from a university-based
      family medicine clinic. Women with a prior diagnosis of osteoporosis or those
      taking bone active medications were excluded. MEASUREMENTS: Participants
      completed a questionnaire that contained the ORAI and the SCORE questions; 203
      completed a DXA scan. RESULTS: The sensitivity and specificity for the ORAI
      (0.68, [0.49 to 0.88, 95% CI]; 0.66, [0.59 to 0.73, 95% CI]) and the SCORE
      instrument (0.54, [0.34 to 0.75, 95% CI]; 0.72, [0.65 to 0.78, 95% CI]) differed
      significantly from previous reports. Overall, the accuracy of the ORAI (66.5%)
      and SCORE instrument (70.0%) were similar (McNemar's test P value = .37). The
      accuracy between instruments differed significantly in African-American women
      (McNemar's test, P value <.001). In African Americans, the SCORE instrument
      correctly identified more women without osteoporosis, but missed 70% of those
      with osteoporosis. CONCLUSIONS: The performance of the ORAI and SCORE instrument
      differed significantly from previous reports. Although both can reduce the use of
      DXA scans for screening for osteoporosis, lower sensitivities resulted in
      underrecognition of osteoporosis and may limit their clinical usefulness in an
      ethnically diverse population.

PMID- 16808749
TI  - Correlates of use of antifracture therapy in older women with low bone mineral
      density.
AB  - BACKGROUND: Guidelines exist for treatment of low bone mineral density (BMD).
      Little is known about patient characteristics associated with use of treatment.
      OBJECTIVES: To determine patient-related correlates of medication use following
      screening dual x-ray absorptiometry (DXA) of older adults. DESIGN: Secondary
      analysis of a prospective cohort study. SETTING: Pittsburgh, PA and Memphis, TN.
      PARTICIPANTS: Community-dwelling women between the ages 70 and 79 years enrolled
      in the Health, Aging, and Body Composition (Health ABC) Study. MEASUREMENTS: Risk
      factors for fracture and BMD of the hip were assessed at baseline. Patients and
      their community physicians were supplied the results of the DXA scan.
      Prescription and over-the-counter medication use was collected at annual exams
      for 2 years. RESULTS: Of 1,584 women enrolled in Health ABC, 378 had an
      indication for antifracture therapy and were not receiving such treatment at
      baseline. By the second annual follow-up examination, prescription antiresorptive
      medication was reported in 49 (13.0%), whereas 65 (17.2%) received calcium and/or
      vitamin D supplementation. In adjusted models, the strongest predictor for use of
      any antifracture medicine was presence of osteoporosis [vs osteopenia, odds ratio
      (OR), 2.9 (1.7 to 4.7)], white race [OR, 2.6 (1.5 to 4.8)], and receipt of the
      flu shot [OR, 2.2 (1.3 to 3.8)]. Neither a history of falls nor prior fracture
      was associated with use of antifracture medications. CONCLUSION: Even when
      physicians of study participants were provided with DXA scan results, 70% of
      older high-functioning women with an indication for therapy did not start or
      remain on an antifracture therapy. Substantial room for improvement exists in
      fracture prevention following a diagnosis of low BMD-especially among women with
      a history of falls, prior fractures, and among black women.

PMID- 16808750
TI  - Understanding African Americans' views of the trustworthiness of physicians.
AB  - BACKGROUND: Many scholars have written about the historical underpinnings and
      likely consequences of African Americans distrust in health care, yet little
      research has been done to understand if and how this distrust affects African
      Americans' current views of the trustworthiness of physicians. OBJECTIVE: To
      better understand what trust and distrust in physicians means to African
      Americans. DESIGN: Focus-group study, using an open-ended discussion guide.
      SETTING: Large public hospital and community organization in Chicago, IL.
      PATIENTS: Convenience sample of African-American adult men and women.
      MEASUREMENTS: Each focus group was systematically coded using grounded theory
      analysis. The research team then identified themes that commonly arose across the
      9 focus groups. RESULTS: Participants indicated that trust is determined by the
      interpersonal and technical competence of physicians. Contributing factors to
      distrust in physicians include a lack of interpersonal and technical competence,
      perceived quest for profit and expectations of racism and experimentation during
      routine provision of health care. Trust appears to facilitate care-seeking
      behavior and promotes patient honesty and adherence. Distrust inhibits care
      seeking, can result in a change in physician and may lead to nonadherence.
      CONCLUSIONS: Unique factors contribute to trust and distrust in physicians among
      African-American patients. These factors should be considered in clinical
      practice to facilitate trust building and improve health care provided to African
      Americans.

PMID- 16808751
TI  - Attitudes of urban American Indians and Alaska Natives regarding participation in
      research.
AB  - OBJECTIVE: To determine what factors influence participation in health research
      among American Indians and Alaska Natives. METHODS: Using vignettes that
      described 3 types of research studies (a behavioral intervention trial, a genetic
      association study, and a pharmacotherapy trial), we surveyed 319 patients and 101
      staff from an urban Indian health care facility to ascertain how study design,
      institutional sponsorship, community involvement, human subjects' issues, and
      subject matter influence participation. RESULTS: Overall response rates were 93%
      for patients and 75% for staff. Hypothetical participation was highest for the
      genetic study (patients=64%; staff=48%), followed by the behavioral intervention
      (patients=46%; staff=42%), and the pharmacotherapy trial (patients=32%;
      staff=23%). The odds of participation (odds ratio [OR]) were generally increased
      among patients and staff when the study was conducted by health care providers
      (OR=1.3 to 2.9) and addressed serious health problems (OR=1.2 to 7.2), but were
      decreased if the federal government led the study (OR=0.3 to 0.5),
      confidentiality might be broken (OR=0.1 to 0.3), and compensation was not
      provided (OR=0.5 to 0.7). CONCLUSION: Close attention to study type,
      institutional sponsorship, community involvement, potential risks and benefits,
      and topic are essential to conceptualizing, designing, and implementing
      successful health research with American Indian and Alaska Native populations.

PMID- 16808752
TI  - Primary care provider concerns about management of chronic pain in community
      clinic populations.
AB  - BACKGROUND: Chronic pain is a common patient complaint in primary care, yet
      providers and patients are often dissatisfied with treatment processes and
      outcomes. OBJECTIVE: To assess provider satisfaction with their training for and
      current management of chronic pain in community clinic settings. To identify
      perceived problems with delivering chronic pain treatment and issues with opioid
      prescribing for chronic pain. DESIGN: Mailed survey to primary care providers
      (PCPs) at 8 community clinics. RESULTS: Respondents (N=111) included attendings,
      residents, and nurse practioners (NPs)/physician assistants (PAs). They reported
      37.5% of adult appointments in a typical week involved patients with chronic pain
      complaints. They attributed problems with pain care and opioid prescribing more
      often to patient-related factors such as lack of self-management, and potential
      for abuse of medication than to provider or practice system factors.
      Nevertheless, respondents reported inadequate training for, and low satisfaction
      with, delivering chronic pain treatment. CONCLUSIONS: A substantial proportion of
      adult primary care appointments involve patients with chronic pain complains.
      Dissatisfaction with training and substantial concerns about patient self
      management and about opioid prescribing suggest areas for improving medical
      education and postgraduate training. Emphasis on patient-centered approaches to
      chronic pain management, including skills for assessing risk of opioid abuse and
      addiction, is required.

PMID- 16808753
TI  - A clinician-educator's roadmap to choosing and interpreting statistical tests.
AB  - As educators seek confirmation of successful trainee achievement, medical
      education must move toward a more evidence-based approach to teaching and
      evaluation. Although medical training often provides physicians with a general
      background in biostatistics, many are not prepared to apply these skills. This
      can hinder clinician educators as they wish to develop, analyze and disseminate
      their scholarly work. This paper is intended to be a concise educational tool and
      guide for choosing and interpreting statistical tests aimed toward medical
      education assessment. It includes guidelines and examples that clinician
      educators can use when analyzing and interpreting studies and when writing
      methods and results sections of reports.

PMID- 16808759
TI  - Race, ethnicity, culture, and disparities in health care.

PMID- 16808754
TI  - Is the quality of the patient-provider relationship associated with better
      adherence and health outcomes for patients with HIV?
AB  - PURPOSE: Patient-centeredness, originally defined as understanding each patient
      as a unique person, is widely considered the standard for high-quality
      interpersonal care. The purpose of our study was to examine the association
      between patient perception of being "known as a person" and receipt of highly
      active antiretroviral therapy (HAART), adherence to HAART, and health outcomes
      among patients with HIV. STUDY DESIGN: Cross-sectional analysis. SUBJECTS: One
      thousand seven hundred and forty-three patients with HIV. MEASUREMENTS: Patient
      reports that their HIV provider "knows me as a person" and 3 outcomes: receipt of
      HAART, adherence to HAART, and undetectable serum HIV RNA. RESULTS: Patients who
      reported that their provider knows them "as a person" were more likely to receive
      HAART (60% vs 47%, P<.001), be adherent to HAART (76% vs 67%, P=.007), and have
      undetectable serum HIV RNA (49% vs 39%, P<.001). Patients who reported their
      provider knows them "as a person" were also older (mean 38.0 vs 36.6 years,
      P<.001), reported higher quality-of-life (mean LASA score 71.1 vs 64.8, P<.001),
      had been followed in clinic longer (mean 64.4 vs 61.7 months, P=.008), missed
      fewer appointments (mean proportion missed appointments 0.124 vs 0.144, P<.001),
      reported more positive beliefs about HAART therapy (39% vs 28% strongly believed
      HIV medications could help them live longer, P<.008), reported less social stress
      (50% vs 62% did not eat regular meals, P<.001) and were less likely to use
      illicit drugs or alcohol (22% vs 33% used drugs, P<.001; 42% vs 53% used alcohol,
      P<.001). Controlling for patient age, sex, race/ethnicity, quality-of-life,
      length of time in clinic, missed appointments, health beliefs, social stress, and
      illicit drug and alcohol use, patients who reported their provider knows them "as
      a person" had higher odds of receiving HAART (odds ratio [OR] 1.41, 95%
      confidence interval [CI] 1.19 to 1.65), adhering to HAART (OR 1.33, 95% CI 1.02
      to 1.72), and having undetectable serum HIV RNA (1.20, 95% CI 1.02 to 1.41).
      CONCLUSIONS: We found that a single item measuring the essence of patient
      centeredness-the patients' perception of being "known as a person"-is
      significantly and independently associated with receiving HAART, adhering to
      HAART, and having undetectable serum HIV RNA. These results support the
      hypothesis that the quality of patient-physician relationship is directly related
      to the health of patients.

PMID- 16808760
TI  - Abdominal aortitis due to Streptococcus pneumoniae and Enterobacter aerogenes: a
      case report and review.
AB  - Endovascular infections are 1 cause of fever of unknown origin. We describe a
      diagnostically challenging case of cryptogenic abdominal aortitis from
      Streptococcus pneumoniae and Enterobacter aerogenes. A 72-year-old male presented
      with epigastric pain, fevers, and chills. A computed tomography scan demonstrated
      enlargement and ulceration of the distal abdominal aorta, prompting urgent
      vascular surgery. Intraoperative tissue cultures grew S. pneumoniae and E.
      aerogenes and gatifloxacin was administered for 6 weeks. Spontaneous abdominal
      aortitis is uncommon and usually due to a single pathogen. This is the second
      reported case of polymicrobial infectious aortitis and to date, Enterobacter has
      only been reported in infected aortic grafts. Clinicians should maintain a high
      index of suspicion for infectious aortitis as the mortality, if only treated
      medically, approaches 100%.

PMID- 16808761
TI  - Stauffer's syndrome variant with cholestatic jaundice: a case report.
AB  - Cholestasis is a common feature of several malignant diseases, including
      pancreatic, hepatic, gallbladder, and ampullary carcinomas. It is usually
      secondary to main bile duct obstruction or widespread hepatic metastasis, but it
      can also be a paraneoplastic syndrome of other underlying malignancies.
      Stauffer's syndrome is a rare paraneoplastic manifestation of renal cell
      carcinoma (RCC) that is characterized by elevated alkaline phosphatase,
      erythrocyte sedimentation rate, alpha-2-globulin, and gamma-glutamyl transferase,
      thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly, in the
      absence of hepatic metastasis and jaundice. A rare variant of this syndrome with
      jaundice has recently been described in 3 cases in the literature. We report a
      patient who presented with abdominal pain and cholestatic jaundice in whom RCC
      was incidentally found during initial workup. Jaundice and liver dysfunction
      resolved completely after surgical resection of the tumor. This case illustrates
      the protean manifestations of RCC, and the importance of considering Stauffer's
      syndrome and its variant in the differential diagnosis of anicteric and icteric
      cholestasis, which may allow early recognition and treatment of an underlying
      malignancy.

PMID- 16808762
TI  - Temporal arteritis presenting with gastrointestinal symptoms in a middle aged
      man.
AB  - Giant cell arteritis, also known as temporal arteritis, is a vasculitis of
      unknown etiology that classically involves the wall of the large to medium size.
      We are reporting a case of a young onset temporal arteritis presenting with
      gastrointestinal symptoms. The patient was a 48-year-old male who presented with
      a 2-week history of fever, diffuse abdominal pain, and malaise. He underwent a
      laparoscopic cholecystectomy after findings of elevated bilirubin and alkaline
      phosphatase as well as suspicion of porcelain gallbladder on ultrasound (or
      computed tomography scan). The patient subsequently developed painless,
      intermittent vision loss and unilateral headaches. A work-up included temporal
      artery biopsy, which showed marked lymphocytic infiltrate in the arterial wall
      consistent with temporal arteritis. The presentation of temporal arteritis may be
      atypical. We are reporting a case of temporal arteritis at a young age presenting
      mainly with gastrointestinal symptoms.

PMID- 16808763
TI  - Bilateral facial paralysis: case presentation and discussion of differential
      diagnosis.
AB  - Bilateral facial paralysis is a rare condition and therefore represents a
      diagnostic challenge. We report the case of a 34-year-old healthy woman with
      sequential bilateral facial paralysis as a sole manifestation of sarcoidosis. She
      initially presented with an isolated left sided Bell's palsy without any symptoms
      to suggest alternative diagnoses. Within a month there was progression to
      peripheral facial paresis on the contra lateral side, prompting a diagnosis of
      Lyme disease. Her physical examination and chest x-ray did not reveal any
      clinical evidence of sarcoidosis. After failing to respond to an empiric trial of
      intravenous ceftriaxone for a presumptive diagnosis of Lyme disease, computed
      tomography scan of the chest was ordered which demonstrated bilateral hilar
      lymphadenopathy. Bronchoscopic biopsy confirmed a diagnosis of sarcoidosis. The
      patient then made a complete recovery on steroid therapy. We discuss the
      differential diagnosis of facial diplegia and focus on the clinical presentation,
      diagnosis and treatment of neurosarcoidosis.

PMID- 16808764
TI  - Primary care clinicians treat patients with medically unexplained symptoms: a
      randomized controlled trial.
AB  - OBJECTIVE: There is no proven primary care treatment for patients with medically
      unexplained symptoms (MUS). We hypothesized that a long-term, multidimensional
      intervention by primary care providers would improve MUS patients' mental health.
      DESIGN: Clinical trial. SETTING: HMO in Lansing, MI. PARTICIPANTS: Patients from
      18 to 65 years old with 2 consecutive years of high utilization were identified
      as having MUS by a reliable chart rating procedure; 206 subjects were randomized
      and 200 completed the study. INTERVENTION: From May 2000 to January 2003, 4
      primary care clinicians deployed a 12-month intervention consisting of cognitive
      behavioral, pharmacological, and other treatment modalities. A behaviorally
      defined patient-centered method was used by clinicians to facilitate this
      treatment and the provider-patient relationship. MAIN OUTCOME MEASURE: The
      primary endpoint was an improvement from baseline to 12 months of 4 or more
      points on the Mental Component Summary of the SF-36. RESULTS: Two hundred
      patients averaged 13.6 visits for the year preceding study. The average age was
      47.7 years and 79.1% were females. Using intent to treat, 48 treatment and 34
      control patients improved (odds ratio [OR]=1.92, 95% confidence interval [CI]:
      1.08 to 3.40; P=.02). The relative benefit (relative "risk" for improving) was
      1.47 (CI: 1.05 to 2.07), and the number needed to treat was 6.4 (95% CI: 0.89 to
      11.89). The following baseline measures predicted improvement: severe mental
      dysfunction (P<.001), severe body pain (P=.039), nonsevere physical dysfunction
      (P=.003), and at least 16 years of education (P=.022); c-statistic=0.75.
      CONCLUSION: The first multidimensional intervention by primary care clinicians
      led to clinically significant improvement in MUS patients.

PMID- 16808765
TI  - Diagnosing and managing cutaneous pigmented lesions: primary care physicians
      versus dermatologists.
AB  - BACKGROUND: Primary care physicians (PCPs) are often expected to screen for
      melanomas and refer patients with suspicious pigmented lesions to dermatologists.
      OBJECTIVE: To assess whether there is a difference between dermatologists and
      PCPs in accurately diagnosing melanoma and appropriately managing (based on
      decisions to refer/biopsy) suspicious pigmented lesions. DESIGN, PARTICIPANTS: A
      survey based on a random sample of 30 photographs of pigmented lesions with known
      pathology was administered to 101 dermatologists and 115 PCPs from October 2001
      to January 2003. MEASUREMENTS: Likelihoods that a photographed lesion was
      melanoma and that the lesion should be biopsied/referred were scored on a 1 to 10
      scale. Accuracy of melanoma diagnosis and appropriateness of pigmented lesion
      management were compared between dermatologists and PCPs by using the areas under
      (AUC) the receiver operating characteristic (ROC) curves. RESULTS: Dermatologists
      were superior to PCPs in diagnosing melanomas (AUC 0.89 vs 0.80, P<.001) and
      appropriately managing pigmented lesions (AUC .84 vs 0.76, P<.001). PCPs who
      tended to biopsy lesions themselves did better at managing pigmented lesions than
      PCPs who did not perform biopsies. Dermatology training during residency did not
      significantly improve the diagnostic accuracy of PCPs nor their management of
      pigmented lesions. CONCLUSIONS: Dermatologists have both better diagnostic
      accuracy and ability to manage pigmented lesions than PCPs. Yet, there is a
      shortage of dermatologists to meet the demand of accurate melanoma screening.
      More innovative strategies are needed to better train PCPs and enhance skin
      cancer screening.

PMID- 16808766
TI  - Effect of awareness of language law on language access in the health care
      setting.
AB  - BACKGROUND: Federal law obligates health care providers receiving federal funding
      to ensure language access to limited English-proficient (LEP) individuals who
      cannot communicate with their provider. OBJECTIVE: To determine whether LEP
      individual awareness of this law improved language access through interpreter
      utilization. DESIGN, SETTING, AND PARTICIPANTS: In June 2003, a telephone survey
      of 1,200 Californians was conducted in 11 non-English languages. MEASUREMENTS:
      The survey included items on English proficiency, awareness of language law,
      health care utilization, and communication methods. Language access was defined
      as having a provider who speaks the individual's language (language-concordant)
      or utilizing an interpreter. RESULTS: There were 1,000 LEP participants, of whom
      371 (37%) were aware of the language law. Four hundred and ninety-one (49%) of
      LEP participants had a language-concordant provider. Of the remaining 509 LEP
      participants without a language-concordant provider, 111 (22%) reported
      interpreter utilization in the health care setting. After controlling for age,
      gender, education, income, insurance status, years in the United States, health
      care utilization, and level of English proficiency, awareness of law was not
      associated with interpreter utilization (odds ratio [OR] 0.66; 95% confidence
      interval [CI] 0.38, 1.17; P=.16), but was associated with having a language
      concordant provider (OR 1.64; 95% CI 1.19, 2.26; P=.003). CONCLUSION: Awareness
      of language law is not sufficient to resolve language barriers for LEP
      individuals. Provider and organization level barriers to language access must be
      addressed.

PMID- 16808767
TI  - Effect of implementing pain management standards.
AB  - BACKGROUND: Historical undertreatment of pain among inpatients has resulted in a
      national requirement for pain practice standards. OBJECTIVE: We hypothesized that
      adoption/promulgation of practice standards in January 2003 at 1 suburban
      teaching hospital progressively increased compliance with those standards and
      decreased pain. DESIGN: We retrospectively reviewed medical records each month
      during 2003, when pain standards were adopted with repeated, institution-wide,
      and nursing-unit-based interventions. Also, we reviewed discharges during 1 month
      in adjacent years. PATIENTS: We identified adult patients from 20 medical and
      surgical All-Payer Refined Disease Related Groupings (APRDRGs) in which opiate
      charges were most common in 2003. Among these, we considered patients actually
      receiving opiates and randomly chose equal numbers of matching subjects in each
      month of 2003. Matching was for APRDRG and complexity group. We also matched
      January 2003 discharges with those from January 2001, 2002, and 2004.
      MEASUREMENTS: For each patient, we captured 3 variables measuring standards
      compliance: percentage pain observations reported numerically, number of
      observations, and median time to reassessment after opiates. We also captured 3
      pain variables: median pain score, rate of improvement in pain score, and total
      opiates dispensed. RESULTS: There were 360 qualifying discharges in 2003, and 75
      in the other years. Numeric observations increased 15%, number of assessments
      36%, and reassessment time decreased 60%. All changes were significant but
      occurred before standards implementation. Among pain measures, only rate of pain
      improvement changed, worsening slightly but significantly (-0.02 to -0.005 U/h),
      also before standards. CONCLUSIONS: Implementation of pain practice standards
      affected neither practice nor pain.

PMID- 16808768
TI  - Over and under-utilization of cyclooxygenase-2 selective inhibitors by primary
      care physicians and specialists: the tortoise and the hare revisited.
AB  - OBJECTIVES: To compare prescribing trends and appropriateness of use of
      traditional and cyclooxygenase-2 selective (COX-2) nonsteroidal anti-inflammatory
      drugs (NSAIDs) by primary care physicians (PCPs) and specialists. DESIGN:
      Retrospective cohort study. PATIENTS: One thousand five hundred and seventy-six
      adult patients continuously enrolled for at least 1 year with an independent
      practice association of a University-associated managed care plan who were
      started on a traditional NSAID or a COX-2 inhibitor from 1999 to 2002 and
      received at least 3 separate medication fills. MEASUREMENTS: Physician specialty
      was identified from office visits. Appropriateness of utilization was based on
      gastrointestinal risk characteristics. RESULTS: Primary care patients were
      younger and less likely to have comorbid conditions. Despite similar GI risk, COX
      2 use among patients seen by PCPs was half that of patients seen by specialists
      (21% vs 44%, P<.001). While PCPs overused cyclooxygenase-2-specific inhibitors
      (COX-2s) less often than specialists (19% vs 41%, P<.001), they also tended to
      underuse COX-2s in patients who were at increased GI risk (46% vs 32%, P=.063).
      This represents a 3-fold and 8-fold difference in overuse versus underuse for
      PCPs and specialists, respectively. CONCLUSIONS: Using COX-2s as a model for
      physician adoption of new therapeutic agents, specialists were more likely to use
      these new medications for patients likely to benefit but were also significantly
      more likely to use them for patients without a clear indication. This study
      demonstrates the tension between appropriate adoption of innovative therapies for
      those individuals who would benefit from their use and those individuals who
      would receive no added clinical benefit but would incur added cost and be placed
      at increased risk.

PMID- 16808769
TI  - Communication about behavioral health risks: a study of videotaped encounters in
      2 internal medicine practices.
AB  - BACKGROUND: As behavioral health risks account for the major causes of
      preventable morbidity and mortality in the United States, national guidelines
      recommend that physicians routinely screen patients for risk factors, and counsel
      as appropriate. OBJECTIVES: To assess the scope of health risk screening and
      characterize the communication content of counseling for health behavior change
      in 2 general internal medicine practices. DESIGN AND PARTICIPANTS: We studied
      videotapes of 125 new patient visits to General Internists affiliated with
      academic medical centers in Chicago, IL (70%) and Burlington, VT (30%). All
      videotapes were content analyzed to examine (1) the incidence and outcome of
      screening for diet, exercise, tobacco, alcohol, drugs, sex, seatbelt use, helmet
      use, firearms, smoke detectors, and sun exposure; (2) the content of counseling
      for at-risk behaviors, with a focus on 11 counseling tasks associated with health
      behavior change. RESULTS: Patient age in these 125 initial visits ranged from 22
      to 85 years. Within the 91 visits that included at least 1 screening attempt,
      there were a total of 361 distinct screening discussions (mean=3.9, SD=2.2,
      range=1 to 9). Seventy-four (20.5%) of the 361 screening discussions revealed an
      at-risk behavior. On average, 2.4 of the 11 counseling tasks were accomplished
      for each of the 74 behavioral health risks (SD=2.2, range 0 to 9); only education
      about the problem (56.8%) and general advice about the solution (62.2%) were
      evident in more than half of the counseling attempts. CONCLUSIONS: This
      observational study reveals that communication tasks associated with successful
      counseling were relatively infrequent occurrences during initial visits in 2
      primary care practices.

PMID- 16808770
TI  - Disclosure of medical errors: what factors influence how patients respond?
AB  - BACKGROUND: Disclosure of medical errors is encouraged, but research on how
      patients respond to specific practices is limited. OBJECTIVE: This study sought
      to determine whether full disclosure, an existing positive physician-patient
      relationship, an offer to waive associated costs, and the severity of the
      clinical outcome influenced patients' responses to medical errors. PARTICIPANTS:
      Four hundred and seven health plan members participated in a randomized
      experiment in which they viewed video depictions of medical error and disclosure.
      DESIGN: Subjects were randomly assigned to experimental condition. Conditions
      varied in type of medication error, level of disclosure, reference to a prior
      positive physician-patient relationship, an offer to waive costs, and clinical
      outcome. MEASURES: Self-reported likelihood of changing physicians and of seeking
      legal advice; satisfaction, trust, and emotional response. RESULTS: Nondisclosure
      increased the likelihood of changing physicians, and reduced satisfaction and
      trust in both error conditions. Nondisclosure increased the likelihood of seeking
      legal advice and was associated with a more negative emotional response in the
      missed allergy error condition, but did not have a statistically significant
      impact on seeking legal advice or emotional response in the monitoring error
      condition. Neither the existence of a positive relationship nor an offer to waive
      costs had a statistically significant impact. CONCLUSIONS: This study provides
      evidence that full disclosure is likely to have a positive effect or no effect on
      how patients respond to medical errors. The clinical outcome also influences
      patients' responses. The impact of an existing positive physician-patient
      relationship, or of waiving costs associated with the error remains uncertain.

PMID- 16808771
TI  - Incidence of and factors associated with achieving target lipid levels in
      patients with peripheral arterial disease.
AB  - BACKGROUND: Patients with peripheral arterial disease (PAD) have increased
      mortality compared with patients without PAD. Coronary artery disease (CAD)
      accounts for almost 75% of deaths in PAD patients. Studies suggest that PAD is
      underdiagnosed and atherosclerotic risk factors undertreated when compared with
      CAD. OBJECTIVE: To determine whether cholesterol guidelines are being met in
      patients with PAD and to determine whether any independent factors increase the
      likelihood of reaching goal low-density lipoprotein (LDL). DESIGN: A
      retrospective chart review of subjects diagnosed with PAD in 2001 at 2 Veterans
      Affairs Medical Centers. MEASUREMENTS: Univariate analysis compares baseline
      characteristics between those reaching goal and those who do not. Multivariate
      logistic regression analysis identified predictors of meeting LDL goal among PAD
      patients. RESULTS: Of 315 patients, 62% reached goal LDL. Those more likely to
      reach goal were older, had hypertension, and a history of CAD and stroke.
      Positive predictors of LDL goal were age and CAD, while smoking was a negative
      predictor. CONCLUSION: The majority of veterans with PAD received lipid-lowering
      medication and achieve goal LDL, but they are more likely to do so if they are
      older than 70 and have a history of CAD.

PMID- 16808772
TI  - The impact of a suspicious prostate biopsy on patients' psychological, socio
      behavioral, and medical care outcomes.
AB  - OBJECTIVE: To evaluate the psychological, socio-behavioral, and medical
      implications of apparently false-positive prostate cancer screening results.
      METHODS: One hundred and twenty-one men with a benign prostate biopsy performed
      in response to a suspicious screening test (biopsy group) and 164 men with a
      normal prostate-specific antigen (PSA) test result (normal PSA group) responded
      to a questionnaire 6 weeks, 6 and 12 months after their biopsy or PSA test.
      RESULTS: The mean (+/-SD) age of respondents was 61+/-9 years (range, 41 to 88
      years). One year later, 26% (32/121) of men in the biopsy group reported having
      worried "a lot" or "some of the time" that they may develop prostate cancer,
      compared with 6% (10/164) in the normal PSA group (P<.001). Forty-six percent of
      the biopsy group reported thinking their wife or significant other was concerned
      about prostate cancer, versus 14% in the normal PSA group (P<.001). Medical
      record review showed that biopsied men were more likely than those in the normal
      PSA group to have had at least 1 follow-up PSA test over the year (73% vs 42%,
      P<.001), more likely to have had another biopsy (15% vs 1%, P<.001), and more
      likely to have visited a urologist (71% vs 13%, P<.001). CONCLUSION: One year
      later, men who underwent prostate biopsy more often reported worrying about
      prostate cancer. In addition, there were related psychological, socio-behavioral,
      and medical care implications. These hidden tolls associated with screening
      should be considered in the discussion about the benefits and risks of prostate
      cancer screening.

PMID- 16808773
TI  - The Worcester Venous Thromboembolism study: a population-based study of the
      clinical epidemiology of venous thromboembolism.
AB  - BACKGROUND: While there have been marked advances in diagnostic and therapeutic
      strategies for venous thromboembolism, our understanding of its clinical
      epidemiology is based on studies conducted more than a decade ago. OBJECTIVE: The
      purpose of this observational study was to describe the incidence and attack
      rates of venous thromboembolism in residents of the Worcester Statistical
      Metropolitan Area in 1999. We also describe demographic and clinical
      characteristics, management strategies, and associated hospital and 30-day
      outcomes. DESIGN AND MEASUREMENTS: The medical records of all residents from
      Worcester, MA (2000 census=477,800), diagnosed with International Classification
      of Diseases, 9th revision (ICD-9) codes consistent with possible venous
      thromboembolism during 1999 were independently validated, classified, and
      reviewed by trained abstractors. RESULTS: A total of 587 subjects were enrolled
      with validated venous thromboembolism. The incidence and attack rates of venous
      thromboembolism were 104 and 128 per 100,000 population, respectively. Three
      quarters of patients developed their venous thromboembolism in the outpatient
      setting - a substantial proportion of these patients had undergone recent surgery
      or had a recent prior hospitalization. Less than half of the patients received
      anticoagulant prophylaxis during high-risk periods before their venous
      thromboembolism. Thirty-day rates of venous thromboembolism recurrence, major
      bleeding, and mortality were 4.8%, 7.7%, and 6.6%, respectively. CONCLUSION:
      These data provide insights into recent incidence and attack rates, changing
      patient profiles, management strategies, and subsequent outcomes in patients with
      venous thromboembolism. The underutilization of prophylaxis before venous
      thromboembolism, and relatively high 30-day recurrence rates, suggest a continued
      need for the improvement of venous thromboembolism prophylaxis and management in
      the community.

PMID- 16808774
TI  - A multidimensional integrative medicine intervention to improve cardiovascular
      risk.
AB  - BACKGROUND: Integrative medicine is an individualized, patient-centered approach
      to health, combining a whole-person model with evidence-based medicine.
      Interventions based in integrative medicine theory have not been tested as
      cardiovascular risk-reduction strategies. Our objective was to determine whether
      personalized health planning (PHP), an intervention based on the theories and
      principles underlying integrative medicine, reduces 10-year risk of coronary
      heart disease (CHD). METHODS: We conducted a randomized, controlled trial among
      154 outpatients age 45 or over, with 1 or more known cardiovascular risk factors.
      Subjects were enrolled from primary care practices near an academic medical
      center, and the intervention was delivered at a university Center for Integrative
      Medicine. Following a health risk assessment, each subject in the intervention
      arm worked with a health coach and a medical provider to construct a personalized
      health plan. The plan identified specific health behaviors important for each
      subject to modify; the choice of behaviors was driven both by cardiovascular risk
      reduction and the interests of each individual subject. The coach then assisted
      each subject in implementing her/his health plan. Techniques used in
      implementation included mindfulness meditation, relaxation training, stress
      management, motivational techniques, and health education and coaching. Subjects
      randomized to the comparison group received usual care (UC) without access to the
      intervention. Our primary outcome measure was 10-year risk of CHD, as measured by
      a standard Framingham risk score, and assessed at baseline, 5, and 10 months.
      Differences between arms were assessed by linear mixed effects modeling, with
      time and study arm as independent variables. RESULTS: Baseline 10-year risk of
      CHD was 11.1% for subjects randomized to UC (n=77), and 9.3% for subjects
      randomized to PHP (n=77). Over 10 months of the intervention, CHD risk decreased
      to 9.8% for UC subjects and 7.8% for intervention subjects. Based on a linear
      mixed-effects model, there was a statistically significant difference in the rate
      of risk improvement between the 2 arms (P=.04). In secondary analyses, subjects
      in the PHP arm were found to have increased days of exercise per week compared
      with UC (3.7 vs 2.4, P=.002), and subjects who were overweight on entry into the
      study had greater weight loss in the PHP arm compared with UC (P=.06).
      CONCLUSIONS: A multidimensional intervention based on integrative medicine
      principles reduced risk of CHD, possibly by increasing exercise and improving
      weight loss.

PMID- 16808775
TI  - Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer.
AB  - OBJECTIVE: To evaluate the evidence of the supplements vitamin C and vitamin E
      for treatment and prevention of cancer. METHODS: Systematic review of trials and
      meta-analysis. DATA SOURCES AND MAIN RESULTS: Thirty-eight studies showed scant
      evidence that vitamin C or vitamin E beneficially affects survival. In the ATBC
      Cancer Prevention Study Group, no statistically significant effect of treatment
      was seen for any cancer individually, and our pooled relative risk (regardless of
      tumor type) for alpha-tocopherol alone was 0.91 (95% confidence interval [CI]:
      0.74, 1.12). All cause mortality was not significant. In the Linxian General
      Population Trial, the relative risks for cancer death for vitamin C (combined
      with molybdenum) was 1.06 (95% CI: 0.92, 1.21) and for vitamin E (combined with
      beta-carotene and selenium) was 0.87 (95% CI: 0.76, 1.00). We identified only 3
      studies that reported statistically significant beneficial results: vitamin C (in
      combination with BCG) was found to be beneficial in a single trial of bladder
      cancer and vitamin E (in combination with omega-3 fatty acid) increased survival
      in patients with advanced cancer. In the ATBC trial, in analyses of 6 individual
      cancers, the prevention of prostate cancer in subjects treated with alpha
      tocopherol was statistically significant (RR=0.64, 95% CI: 0.44, 0.94).
      CONCLUSIONS: The systematic review of the literature does not support the
      hypothesis that the use of supplements of vitamin C or vitamin E in the doses
      tested helps prevent and/or treat cancer in the populations tested. There were
      isolated findings of benefit, which require confirmation.

PMID- 16808776
TI  - Factors associated with the hospitalization of low-risk patients with community
      acquired pneumonia in a cluster-randomized trial.
AB  - BACKGROUND: Many low-risk patients with pneumonia are hospitalized despite
      recommendations to treat such patients in the outpatient setting. OBJECTIVE: To
      identify the factors associated with the hospitalization of low-risk patients
      with pneumonia. METHODS: We analyzed data collected by retrospective chart review
      for 1,889 low-risk patients (Pneumonia Severity Index [PSI] risk classes I to III
      without evidence of arterial oxygen desaturation) enrolled in a cluster
      randomized trial conducted in 32 emergency departments. RESULTS: Overall, 845
      (44.7%) of all low-risk patients were treated as inpatients. Factors
      independently associated with an increased odds of hospitalization included PSI
      risk classes II and III, the presence of medical or psychosocial
      contraindications to outpatient treatment, comorbid conditions that were not
      contained in the PSI (cognitive impairment, history of coronary artery disease,
      diabetes mellitus, or pulmonary disease), multilobar radiographic infiltrates,
      and home therapy with oxygen, corticosteroids, or antibiotics before
      presentation. While 32.8% of low-risk inpatients had a contraindication to
      outpatient treatment and 47.1% had one or more preexisting treatments, comorbid
      conditions, or radiographic abnormalities not contained in the PSI, 20.1% had no
      identifiable risk factors for hospitalization other than PSI risk class II or
      III. CONCLUSIONS: Hospital admission appears justified for one-third of low-risk
      inpatients based upon the presence of one or more contraindications to outpatient
      treatment. At least one-fifth of low-risk inpatients did not have a
      contraindication to outpatient treatment or an identifiable risk factor for
      hospitalization, suggesting that treatment of a larger proportion of such low
      risk patients in the outpatient setting could be achieved without adversely
      affecting patient outcomes.

PMID- 16808777
TI  - Nicotine replacement therapy: patterns of use after a quit attempt among
      methadone-maintained smokers.
AB  - AIM: To determine the association between daily smoking and use of nicotine
      replacement therapy (NRT), and to determine predictors of greater NRT use among
      methadone-maintained smokers. INTERVENTION: Assignment to free nicotine patch (8
      to 12 weeks) plus either (1) a baseline-tailored brief motivational intervention,
      a quit date behavioral skills counseling session, and a relapse prevention follow
      up session (max), or (2) brief advice using NCI's 4 A's model (min). SETTING:
      Five methadone maintenance treatment centers. PARTICIPANTS: Of the 383 methadone
      maintained smokers enrolled, 309 (80.6%) set a specific quit date (received NRT)
      and were located for assessments. Participants were 51.8% male, 78.6% Caucasian,
      and smoked 26.6 (SD=12.2) cigarettes/day. OUTCOME: Use of NRT and smoking
      behaviors during the 180-day follow-up period assessed by the Timeline follow
      back method. FINDINGS: On the day following their quit day, 86.4% of participants
      used NRT. The percentage of participants using NRT was 52.3%, 27.1%, and 10.4% on
      day 30, day 60, and day 90, respectively. Participants used NRT on 44.1% of the
      days through the 90 days of the treatment protocol. The estimated odds of smoking
      abstinence was 7.1 (P<.001) times higher on days when NRT was used than on days
      when NRT was not used, and cigarettes/day was also significantly lower on NRT
      days (14.93 vs 4.65; P<.001). CONCLUSION: Nicotine replacement therapy use was
      inconsistent following an initial quit attempt among methadone-maintained
      smokers. On days when NRT was used, individuals were likely to smoke at reduced
      levels or not at all.

PMID- 16808778
TI  - Residents' perceptions of professionalism in training and practice: barriers,
      promoters, and duty hour requirements.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education duty hour
      requirements may affect residents' understanding and practice of professionalism.
      OBJECTIVE: We explored residents' perceptions about the current teaching and
      practice of professionalism in residency and the impact of duty hour
      requirements. DESIGN: Anonymous cross-sectional survey. PARTICIPANTS: Internal
      medicine, neurology, and family practice residents at 3 teaching hospitals
      (n=312). MEASUREMENTS: Using Likert scales and open-ended questions, the
      questionnaire explored the following: residents' attitudes about the principles
      of professionalism, the current and their preferred methods for teaching
      professionalism, barriers or promoters of professionalism, and how implementation
      of duty hours has affected professionalism. RESULTS: One hundred and sixty-nine
      residents (54%) responded. Residents rated most principles of professionalism as
      highly important to daily practice (91.4%, 95% confidence interval [CI] 90.0 to
      92.7) and training (84.7%, 95% CI 83.0 to 86.4), but fewer rated them as highly
      easy to incorporate into daily practice (62.1%, 95% CI 59.9 to 64.3),
      particularly conflicts of interest (35.3%, 95% CI 28.0 to 42.7) and self
      awareness (32.0%, 95% CI 24.9 to 39.1). Role-modeling was the teaching method
      most residents preferred. Barriers to practicing professionalism included time
      constraints, workload, and difficulties interacting with challenging patients.
      Promoters included role-modeling by faculty and colleagues and a culture of
      professionalism. Regarding duty hour limits, residents perceived less time to
      communicate with patients, continuity of care, and accountability toward their
      colleagues, but felt that limits improved professionalism by promoting resident
      well-being and teamwork. CONCLUSIONS: Residents perceive challenges to
      incorporating professionalism into their daily practice. The duty hour
      implementation offers new challenges and opportunities for negotiating the
      principles of professionalism.

PMID- 16808779
TI  - Prevalence of torture survivors among foreign-born patients presenting to an
      urban ambulatory care practice.
AB  - BACKGROUND: The prevalence of torture among foreign-born patients presenting to
      urban medical clinics is not well documented. OBJECTIVE: To determine the
      prevalence of torture among foreign-born patients presenting to an urban primary
      care practice. DESIGN: A survey of foreign-born patients. PATIENTS: Foreign-born
      patients, age > or = 18, presenting to the Primary Care Clinic at Boston Medical
      Center. MEASUREMENTS: Self-reported history of torture as defined by the UN, and
      history of prior disclosure of torture. RESULTS: Of the 308 eligible patients, 88
      (29%) declined participation, and 78 (25%) were not included owing to lack of a
      translator. Participants had a mean age of 47 years (range 19 to 76), were mostly
      female (82/142, 58%), had been in the United States for an average of 14 years
      (range 1 month to 53 years), and came from 35 countries. Fully, 11% (16/142, 95
      percent confidence interval 7% to 18%) of participants reported a history of
      torture that was consistent with the UN definition of torture. Thirty-nine
      percent (9/23) of patients reported that their health care provider asked them
      about torture. While most patients (15/23, 67%) reported discussing their
      experience of torture with someone in the United States, 8 of 23 (33%) reported
      that this survey was their first disclosure to anyone in the United States.
      CONCLUSION: Among foreign-born patients presenting to an urban primary care
      center, approximately 1 in 9 met the definition established by the UN Convention
      Against Torture. As survivors of torture may have significant psychological and
      physical sequelae, these data underscore the necessity for primary care
      physicians to screen for a torture history among foreign-born patients.

PMID- 16808781
TI  - BRIEF REPORT: the aging of the homeless population: fourteen-year trends in San
      Francisco.
AB  - BACKGROUND: Homelessness is associated with high rates of health and substance
      use problems. OBJECTIVE: To examine trends in the age, housing, health status,
      health service utilization, and drug use of the homeless population over a 14
      year period. DESIGN: Serial cross-sectional. PARTICIPANTS: We studied 3,534
      literally homeless adults recruited at service providers in San Francisco in 4
      waves: 1990-1994, 1996-1998, 1999-2000, and 2003. MEASUREMENTS: Age, time
      homeless, self-reported chronic conditions, hospital and emergency department
      utilization, and drug and alcohol use. RESULTS: The median age of the homeless
      increased from 37 to 46 over the study waves, at a rate of 0.66 years per
      calendar year (P<.01). The median total time homeless increased from 12 to 39.5
      months (P<.01). Emergency department visits, hospital admissions, and chronic
      health conditions increased. CONCLUSIONS: The homeless population is aging by
      about two thirds of a year every calendar year, consistent with trends in several
      other cities. It is likely that the homeless are static, aging population cohort.
      The aging trends suggest that chronic conditions will become increasingly
      prominent for homeless health services. This will present challenges to
      traditional approaches to screening, prevention, and treatment of chronic
      diseases in an aging homeless population.

PMID- 16808780
TI  - BRIEF REPORT: nutrition and weight loss information in a popular diet book: is it
      fact, fiction, or something in between?
AB  - BACKGROUND/OBJECTIVE: Diet books dominate the New York Times Advice Best Seller
      list and consumers cite such books as an important source of nutrition
      information. However, the scientific support for nutrition claims presented as
      fact (nutrition facts) in diet books is not known. DESIGN/MEASUREMENTS: We
      assessed the quality of nutrition facts in the best-selling South Beach Diet
      using support in peer-reviewed literature as a measure of quality. We performed
      structured literature searches on nutrition facts located in the books' text, and
      then assigned each fact to 1 of 4 categories (1) fact supported, (2) fact not
      supported, (3) fact both supported and not supported, and (4) no related papers.
      A panel of expert reviewers adjudicated the findings. RESULTS: Forty-two
      nutrition facts were included. Fourteen (33%) facts were supported, 7 (17%) were
      not supported, 18 (43%) were both supported and not supported, and 3 (7%) had no
      related papers, including the fact that the diet had been "scientifically studied
      and proven effective." CONCLUSIONS: Consumers obtain nutrition information from
      diet books. We found that over 67% of nutrition facts in a best-seller diet book
      may not be supported in the peer-reviewed literature. These findings have
      important implications for educating consumers about nutrition information
      sources.

PMID- 16808782
TI  - "Why take it if you don't have anything?" breast cancer risk perceptions and
      prevention choices at a public hospital.
AB  - BACKGROUND: Despite advances in breast cancer risk assessment and risk reduction
      technologies, little is still known about how high-risk women make sense of their
      risk and assess prevention options, particularly among minority and low-income
      women. Qualitative methods explore the complex meanings and logics of risk and
      prevention that quantitative approaches overlook. OBJECTIVE: This study examined
      how women attending a high risk breast cancer clinic at a public hospital
      conceptualize their breast cancer risk and think about the prevention options
      available to them. METHODS: Semi-structured interviews were used to gather data
      from 33 high-risk women (75% African American) between May and August 2004.
      Interview transcripts were analyzed for recurrent themes and patterns. RESULTS:
      Despite general awareness of their objective risk status, many women in this
      study reported they did not feel "high risk" because they lacked signs and
      symptoms of cancer. Risk was described as an experienced acute problem rather
      than a statistical possibility. Women also frequently stated that thinking about
      cancer might cause it to happen and so it is better not to "dwell on it." While
      screening was welcomed, women were generally skeptical about primary prevention.
      In particular, preventive therapies were perceived to cause problems and were
      only acceptable as treatment options for a disease. CONCLUSIONS: The body of
      ideas about risk and prevention expressed by this population differ from the
      medical model. These findings have implications for risk perception research as
      well as for the efficacy of risk communication and prevention counseling in
      clinical contexts.

PMID- 16808783
TI  - Linguistic disparities in health care access and health status among older
      adults.
AB  - BACKGROUND: English proficiency may be important in explaining disparities in
      health and health care access among older adults. SUBJECTS: Population-based
      representative sample (N=18,659) of adults age 55 and older from the 2001
      California Health Interview Survey. METHODS: We examined whether health care
      access and health status vary among older adults who have limited English
      proficiency (LEP), who are proficient in English but also speak another language
      at home (EP), and who speak English only (EO). Weighted bivariate and
      multivariate survey logit analyses were conducted to examine the role of language
      ability on 2 aspects of access to care (not having a usual source of care, delays
      in getting care) and 2 indicators of health status (self-rated general health and
      emotional health). RESULTS: Limited-English proficient adults were significantly
      worse off (1.68 to 2.49 times higher risk) than EO older adults in 3 of our 4
      measures of access to care and health status. Limited-English proficient older
      adults had significantly worse access to care and health status than EP older
      adults except delays in care. English proficient adults had 52% increased risk of
      reporting poorer emotional health compared with EO speakers. CONCLUSIONS:
      Provision of language assistance services to patients and training of providers
      in cultural competence are 2 means by which health care systems could reduce
      linguistic barriers, improve access to care, and ultimately improve health status
      for these vulnerable populations.

PMID- 16808784
TI  - International Clinical Epidemiology Network: an opportunity for SGIM
      international cooperation.
AB  - The Canadian/American regional group of the International Clinical Epidemiology
      Network (INCLEN) invites SGIM members to join in an international network
      dedicated to improving health in low and middle-income countries and reducing
      health disparities in North America-not only because many goals and activities of
      the 2 organizations are compatible such as evidence-based medicine, mentoring,
      and training; but because collaboration between SGIM and INCLEN could strengthen
      both groups. With increasing brain drain from the developing world to the North,
      there is an ever-increasing need for academic contributions from the North to
      swing the balance toward brain gain for the South. SGIM members have the academic
      expertise to make an important contribution to global health. Participation and
      contribution from SGIM members is welcomed at the individual or organizational
      level. We invite you to explore possible partnership and collaboration.

PMID- 16808789
TI  - Managing somatization: medically unexplained should not mean medically ignored.

PMID- 16808790
TI  - Melanoma: is more diagnosis better?

PMID- 16808791
TI  - RCC special issue inspiring.

PMID- 16808792
TI  - NSAID-induced gastrointestinal damage: current clinical management and
      recommendations for prevention.
AB  - Gastrointestinal toxicity is a common adverse effect of traditional non-steroidal
      anti-inflammatory drugs (NSAIDs) and patients at risk should receive prevention
      therapies. Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) are safer to
      the gastrointestinal tract than traditional NSAIDs. Current prevention strategies
      in patients who need NSAIDs should also take into account the presence of
      cardiovascular risk factors, as coxibs and probably most traditional NSAIDs
      increase the incidence of serious cardiovascular events. Patients without risk
      factors should be treated with traditional NSAIDs, whereas patients at risk may
      receive cotherapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib
      alone. However, patients with a previous bleeding ulcer should receive the
      combination of a coxib plus a PPI, and Helicobacter pylori should be tested for
      and treated if present. Coxib and NSAID therapy should be prescribed with caution
      in patients with increased cardiovascular risk and should be prescribed at the
      lowest possible dose and for the shortest period of time. These patients will
      probably be treated with low-dose aspirin or other antiplatelet agents, which
      puts them at increased risk of upper gastrointestinal complications. The risk of
      gastrointestinal toxicity with combined therapy of aspirin and coxib may be lower
      than that with traditional NSAIDs plus aspirin, but all these patients may
      benefit from PPI cotherapy. When the lower gastrointestinal tract is of concern,
      coxib instead of NSAID therapy should be considered. Coxib therapy has better
      gastrointestinal tolerance than traditional NSAIDs and PPI therapy is effective
      both in the treatment and prevention of NSAID-induced dyspepsia and should be
      considered in patients who develop dyspepsia during NSAID or coxib therapy.

PMID- 16808793
TI  - Chemopreventive effects of rofecoxib and folic acid on gastric carcinogenesis
      induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.
AB  - OBJECTIVES: Epidemiological and experimental studies indicate that non-steroidal
      anti-inflammatory drugs (NSAIDs) are chemopreventive agents of gastrointestinal
      cancers, but few studies on gastric cancer have been carried out. A decrease in
      folic acid supplement and subsequent DNA hypomethylation are related to
      gastrointestinal cancers, and it has been shown that high-dose folic acid may
      interfere with gastric carcinogenesis in dogs. The objective of this study was to
      investigate the effects of rofecoxib, a selective cyclooxygenase-2 (COX-2)
      inhibitor, and folic acid on the chemoprevention of gastric cancer induced by N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, and to evaluate the
      cell proliferation of gastric mucosa in different experimental groups. METHODS:
      Eighty male Wistar rats were randomly divided into five groups (16 rats in each
      group). In the control group, the rats were given pure water and basal diet. In
      the MNNG group, the rats received MNNG in drinking water (100 mg/L) and basal
      diet. In the MNNG + low-dose rofecoxib group, the rats were given MNNG and
      rofecoxib 5 mg/kg per day with basal diet. In the MNNG + high-dose rofecoxib
      group, the rats were given MNNG and rofecoxib 15 mg/kg per day with basal diet.
      In the MNNG + folic acid group, the rats were given MNNG and folic acid 5 mg/kg
      per day with basal diet. The experiment was terminated at 50 weeks, and all rats
      were killed. Blood samples of 3 mL were obtained for measurement of serum folic
      acid concentrations in the control group, the MNNG group and the MNNG + folic
      acid group by using chemiluminescent method. The stomach was removed from all
      rats for histopathological examination and immunohistochemical study.
      Proliferating cell nuclear antigen (PCNA) expression in gastric epithelial cells
      was also determined. RESULTS: In the MNNG group, five of 11 rats (45.5%)
      developed gastric cancer, while in all other four groups no gastric cancer was
      found (P < 0.05). The positivity rate of PCNA expression in the cancerous tissues
      was significantly higher than that in the non-cancerous tissues (80.0%vs 14.1%, P
      < 0.05). The positivity rate of PCNA expression in the gastric mucosal cells of
      the MNNG group was significantly higher than that in the other four groups. The
      mean serum folic acid concentration of rats was significantly higher in the MNNG
      + folic acid group (193.70 +/- 60.73 ng/mL) than those in the control group
      (84.21 +/- 25.26 ng/mL) and the MNNG group (72.27 +/- 16.70 ng/mL, P < 0.05). It
      was shown that both low- and high-dose rofecoxib as well as folic acid interfered
      with the development of gastric cancer induced by MNNG in Wistar rats.
      CONCLUSIONS: The results indicate that rofecoxib as well as folic acid interferes
      with gastric carcinogenesis induced by MNNG in Wistar rats, and the suppression
      of gastric cell proliferation may play a crucial role in the chemoprevention of
      gastric cancer by rofecoxib and folic acid. The higher serum folic acid
      concentration of rats may play an important role in the prevention of gastric
      cancer.

PMID- 16808794
TI  - Additional bedtime H2-receptor antagonist for the control of nocturnal gastric
      acid breakthrough: a Cochrane systematic review.
AB  - OBJECTIVES: To assess the effectiveness and safety of additional bedtime H(2)
      receptor antagonists (H(2)RAs) in suppressing nocturnal gastric acid breakthrough
      (NAB) via a systematic review. METHODS: Eligible trials were identified by
      searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane
      Library Issue 2, 2004), MEDLINE (January 1966-June 2004), EMBASE (January 1980
      June 2004) and CINAHL (January 1982-June 2004). Additional hand-searching was
      conducted on the proceedings of correlated conferences, eight important Chinese
      journals and references of all included trials. All randomized controlled trials
      evaluating H(2)RAs for the control of NAB were eligible for inclusion. The
      systematic review was conducted using methods recommended by The Cochrane
      Collaboration. RESULTS: Only two randomized crossover studies, comprising 32
      participants, met the inclusion criteria. Because the design, dosage and duration
      of the treatments were different between the studies, it was not possible to
      conduct meta-analysis. There were no consistent conclusions found between the two
      included studies in evaluating H(2)RAs for the control of NAB. CONCLUSIONS: No
      implications for practice at this stage can be concluded. Appropriately designed
      large-scale randomized controlled trials with long-term follow up are needed to
      determine the effects of additional bedtime H(2)RAs in suppressing NAB.

PMID- 16808796
TI  - Differentiation potential of bone marrow stromal cells to enteric neurons in
      vitro.
AB  - OBJECTIVE: To investigate whether bone marrow stromal cells (BMSC) can be induced
      to differentiate into enteric neurons and to produce more nerve growth factor
      (NGF) and glial cell line-derived neurotrophic factor (GDNF). METHODS: Bone
      marrow stromal cells were harvested from male Sprague-Dawley rats and cultured in
      Dulbecco's modified eagle medium supplemented with 20% fetal bovine serum. The
      BMSC were passaged six times and characterized by flow cytometry. The BMSC were
      pre-induced by basic fibroblast growth factor (10 ng/mL) for 24 h, then induced
      with GDNF in fetal gut condition medium (FGCM) for 10 days. The expressions of
      neuronal markers neural specific enolase (NSE), neurofilament (NF), glial cell
      marker, glial fibrillary acedic protein (GFAP), and enteric neuronal marker
      protein gene product 9.5 (PGP9.5), neural nitric oxide synthase (nNOS), and
      enteric neural transmitter vasoactive intestinal polypeptide (VIP) were detected
      by fluorescent immunohistochemistry. Expression levels of GDNF and NGF mRNA were
      determined by RT-PCR. RESULTS: The cultured BMSC were CD90 (99.7%) positive and
      CD45 negative on flow cytometry. At day 10 of induction, 58.5 +/- 10.8% cells
      adopted neuron-like morphological changes and showed expression of NSE (47.6 +/-
      7.5%), NF (75.6 +/- 8.4%), GFAP (negative), PGP9.5 (57.7 +/- 6.5%), nNOS (46.6 +/
      5.4%) and VIP (72.3 +/- 6.7%) by immunofluorescence. The BMSC expressed low
      levels of NGF and GDNF mRNA; however, after induction of GDNF in FGCM, the
      expression levels of NGF and GDNF mRNA were significantly increased. CONCLUSION:
      Bone marrow stromal cells have the potential to be induced to differentiate into
      enteric neurons, express enteric neural transmitters, and produce more NGF and
      GDNF. Therefore, BMSC could be used as new method to treat gastrointestinal
      motility disorders associated with enteric neural lesions.

PMID- 16808795
TI  - Effects of acute and chronic restraint stress on visceral sensitivity and
      neuroendocrine hormones in rats.
AB  - OBJECTIVE: To investigate the effects of acute and chronic partial restraint
      stress (PRS) on visceral sensitivity to colorectal distention and the
      neuroendocrine response in rats. METHODS: Male Sprague-Dawley rats were used in
      this study. The abdominal withdrawal reflex score was assessed before stress,
      immediately after acute or chronic PRS, and 7 days after the first stress. The
      plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH)
      were detected by radioimmunoassay at different time points. RESULTS: The
      abdominal withdrawal reflex scores of the rats with acute or chronic PRS were
      significantly higher immediately after stress than those before and 7 days after
      the stress (P < 0.05). The levels of CORT (25.35 +/- 6.03 ng/mL) and ACTH (312.47
      +/- 50.76 pg/mL) in rats with acute PRS showed a significant elevation
      immediately after stress compared to rats without PRS (7.24 +/- 2.97 ng/mL, 97.00
      +/- 23.33 pg/mL, P < 0.05). However, these hormones returned to the baseline
      value 7 days after acute PRS. The levels of CORT (20.84 +/- 2.19 ng/mL) and ACTH
      (200.41 +/- 78.10 pg/mL) in rats with chronic PRS were significantly higher after
      stress than in rats without PRS (P < 0.05), and these hormones remained elevated
      7 days after chronic PRS. CONCLUSIONS: Both acute and chronic PRS induce
      reversible visceral hypersensitivity. Acute PRS transiently elevates the plasma
      levels of CORT and ACTH, whereas chronic PRS has a longer term effect.

PMID- 16808797
TI  - Alteration of the pancreatic endocrine component in the early stage of acute
      necrotic pancreatitis in rats.
AB  - OBJECTIVE: To investigate alterations of the pancreatic endocrine component in
      the early stage of acute necrotic pancreatitis (ANP) in rats. METHODS: Thirty-six
      Sprague-Dawley rats were randomly allocated to two groups: ANP group (n = 18) and
      sham-operated (control) group (n = 18). ANP was induced by retrograde injection
      of 4% sodium deoxycholate (40 mg/kg, 0.1 mL/min) into the biliopancreatic duct
      and the severity of pancreatitis induced was assessed by histopathological
      examination and level of plasma amylase. The pancreatic endocrine function was
      assessed by measuring the levels of plasma glucose and insulin and by measuring
      the insulin content in pancreatic beta cells by immunofluorescence and
      immunocytochemistry. RESULTS: Five hours after operation, the pancreas of rats in
      the ANP group showed pathological changes with edema, hemorrhage, fatty necrosis,
      acinar destruction and leukocyte infiltration in the exocrine portion of the
      pancreas. Plasma amylase activity increased significantly (P < 0.01) and bloody
      ascites appeared in the abdominal cavity. Nevertheless the endocrine islets
      appeared normal and the beta cells contained intensive labeling of insulin.
      Levels of glucose and insulin in plasma increased significantly. In the ANP
      group, 5 h after operation the plasma level of glucose was 8.18 +/- 2.26 mmol/L
      vs 6.39 +/- 1.26 mmol/L, and of insulin was 23.27 +/- 3.50 MIU/L vs 18.40 +/-
      3.98 MIU/L. In the control group, 5 h after operation the plasma level of glucose
      was 9.39 +/- 0.62 mmol/L vs 5.89 +/- 0.62 mmol/L, and of insulin was 26.28 +/-
      4.77 MIU/L vs 12.89 +/- 2.05 MIU/L; there was no significant difference between
      these two groups (P > 0.05). After a bolus injection of glucose, however, a much
      higher level of insulin was found in the control group (35.30 +/- 5.05 MIU/L)
      than that in the ANP group (23.91 +/- 4.62 MIU/L, P < 0.05). CONCLUSIONS: There
      may be an impaired ability of insulin release in response to glucose stimulation
      in the early stage of ANP, although the morphology of the pancreatic endocrine
      component remains intact.

PMID- 16808798
TI  - Evaluation of the diagnostic value of serum tumor markers, and fecal k-ras and
      p53 gene mutations for pancreatic cancer.
AB  - OBJECTIVE: To evaluate the diagnostic value for pancreatic cancer of four serum
      tumor markers, carbohydrate antigen (CA) 199, CA242, CA50 and carcino-embryonic
      antigen (CEA), and fecal k-ras and p53 gene mutations. METHODS: From February
      2002 to March 2004, 136 patients were consecutively diagnosed with pancreatic
      cancer in the three participating medical centers. The diagnosis was confirmed by
      pathology in 53 patients, of whom five were excluded because they did not have
      measurement of serum tumor marker. The remaining 48 patients comprised the case
      group in the study. Ninety-six patients with benign digestive diseases diagnosed
      during the same period were recruited as control subjects. They were matched by
      sex and age. In both groups, serum CA199, CA242, CA50 and CEA were measured by
      ELISA, and fecal k-ras and p53 gene mutations were measured by PCR-restriction
      fragment length polymorphism and PCR-single strand conformational polymorphism,
      respectively. The receiver operating characteristic (ROC) curve and area under
      the curve (AUC) were used to compare their diagnostic value, as well as the
      sensitivity, specificity and likelihood ratio. Moreover, independent and
      sensitive tests from these non-invasive approaches were selected to form a
      parallel test that may have further improved sensitivity for diagnosis of
      pancreatic cancer. RESULTS: The AUC of serum CA199 and CA242 were 0.821 (95%CI
      0.725-0.917) and 0.821 (95%CI 0.723-0.919), respectively. The optimal diagnostic
      value of serum CA199 for pancreatic cancer was 93 U/mL, with a sensitivity of
      73.7% and specificity of 91.4%. The positive likelihood ratio of CA199 was 8.57,
      and the negative likelihood ratio was 0.29. The optimal diagnostic value of serum
      CA242 was 25 U/mL, with a sensitivity of 71.1% and specificity of 93.5%. The
      positive likelihood ratio of CA242 was 10.94, and the negative likelihood ratio
      was 0.31. The sensitivity of fecal k-ras gene mutation for diagnosis of
      pancreatic cancer was 77.4%, and the specificity was 81.2%. The positive and
      negative likelihood ratios of fecal k-ras gene mutation were 4.12 and 0.28,
      respectively. The sensitivity and specificity of fecal p53 gene mutation were
      25.8% and 95.3%, respectively, and its positive and negative likelihood ratios
      were 5.49 and 0.78. The rate of fecal k-ras mutation was higher in patients with
      benign pancreatic diseases (57.14%) than that of controls with non-pancreatic
      disorders. The values of serum tumor markers and fecal k-ras and p53 gene
      mutation rates were not significantly different in subgroups according to site or
      stage of pancreatic cancer. The sensitivity and specificity of the parallel test
      of serum CA199 and fecal k-ras gene mutation were 94.06% and 74.22%,
      respectively, while the sensitivity and specificity of the parallel test of serum
      CA242 and fecal k-ras were 93.47% and 75.92%, respectively. CONCLUSIONS: Serum
      CA199 and CA242 are valuable diagnostic tools for pancreatic cancer. The
      diagnostic value is further improved when they are combined with fecal k-ras gene
      mutation measurement.

PMID- 16808799
TI  - Histopathological study of vascular changes after intra-arterial and intravenous
      injection of N-butyl-2-cyanoacrylate.
AB  - OBJECTIVE: To assess the histopathological vascular changes after injection of N
      butyl-2-cyanoacrylate into the vessels of adult rabbits. METHODS: The animals
      used were 42 pure-blood New Zealand white rabbits weighing 2-3 kg. 0.2 mL
      cyanoacrylate with lipiodol was injected into the external jugular vein and
      femoral artery of each rabbit. Tissue specimens were obtained for
      histopathological study at 3 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 2 months
      and 3 months after injection. RESULTS: The vessels were obliterated immediately
      after the injection. The main manifestation of histopathology at 3 days to 2
      weeks was an acute inflammatory reaction; this progressed to subacute vasculitis
      at 3 weeks and a chronic granulomatous foreign body reaction developed at 4
      weeks. The glue mass essentially disappeared in 2-3 months, replaced by fibrotic
      tissue with partial vascular recanalization. At 3 weeks after injection, the
      elastic fibrils of the arterial wall proliferated distinctly, resulting in
      narrowing of the lumen with subsequent obliteration, whereas the venous wall
      still showed inflammation and necrosis without hyperplasia of elastic fibrils.
      Extrusion of glue was observed over 1-3 months in both arteries and veins and was
      obvious in the latter. CONCLUSIONS: The histopathological changes after injection
      of N-butyl-2-cyanoacrylate were similar in the arteries and the veins with the
      exception of hyperplasia of elastic fibrils in the arterial wall and inflammation
      and necrosis in the venous wall at 2-3 weeks. Glue extrusion was seen in both
      arteries and veins.

PMID- 16808800
TI  - Pain and quality of life for patients with venous leg ulcers: proof of concept of
      the efficacy of Biatain-Ibu, a new pain reducing wound dressing.
AB  - Wound pain is a serious problem for elderly patients suffering from chronic leg
      ulcers, and it may lead to reduced wound healing rates and reduced quality of
      life. Biatain-Ibu Non-adhesive (Coloplast A/S), a new pain-reducing moist wound
      healing dressing containing ibuprofen was tested for pain reduction, safety, and
      efficacy on 10+2 patients in a single-blinded crossover study against Biatain Non
      adhesive (Coloplast A/S). Pain was measured with a Numeric Box Scale before,
      during, and after dressing change. Quality of life was measured using the World
      Health Organization-5 Well-Being Index. Dressing moist wound healing properties
      such as absorption capacity and leakage were tested together with assessment of
      wound exudate and blood plasma content of ibuprofen. Use of the Biatain-Ibu foam
      dressing correlated with a decrease in pain intensity scores from 7 in the run-in
      period to approximately 2.5 in the Biatain-Ibu treatment phase. Quality of life
      measures were improved which together with the reduced pain could contribute to
      faster wound healing. The moist wound healing properties of Biatain-Ibu were
      similar to that of the Biatain Non-adhesive and ulcer size was reduced by 24%
      during the treatment period. Neither side effects nor systemic plasma
      concentrations of ibuprofen were observed. These data indicate that Biatain-Ibu
      could reduce persistent and temporary wound pain, increase Quality of life, was
      found safe to use, and had excellent moist wound healing properties.

PMID- 16808801
TI  - The effect of amelogenins (Xelma) on hard-to-heal venous leg ulcers.
AB  - With an aging population venous ulceration is likely to become an increasing
      problem. Despite improvements in care and the widespread introduction of
      compression bandaging, the mainstay of current management, a significant
      proportion of venous leg ulcers remain hard to heal. Therefore, a single-blinded,
      randomized multicenter study was performed to compare wound size reduction using
      amelogenin proteins (Xelma) formulated into a solution which forms a temporary
      extracellular matrix on contact with the wound bed. Propylene glycol alginate 7%
      served as a control. Patients were randomized to receive either amelogenin
      protein or control treatment. The investigational products were applied weekly
      under soft silicone secondary dressings for up to a maximum of 12 weeks.
      Compression therapy was maintained throughout the investigation. Wound size
      reduction was measured by tracing and all wounds were photographed. In total 123
      patients were recruited, 62 patients in the amelogenin group, and 61 in the
      control group, respectively. Subgroup analyses were performed for ulcers with a
      size>10 cm2 at baseline and for ulcers of duration of >12 months. The wound size
      reduction was greatest in the group treated with amelogenin (33.8 vs. 25.6%,
      n=117), this difference being greatest for larger ulcers (25 vs. 7.9% for
      ulcers>10 cm(2), n=61) and those of long duration (29.3 vs. 10.9% for ulcers>12
      month duration, n=61). We conclude that this product may be clinically useful in
      the treatment of these venous leg ulcers.

PMID- 16808802
TI  - Transdermal nicotine patch enhances type I collagen synthesis in abstinent
      smokers.
AB  - Cigarette smokers deposit less collagen, expressed as hydroxyproline, in
      granulation tissue than nonsmokers. We studied the effect of abstinence from
      smoking and transdermal nicotine patches on deposition of hydroxyproline,
      proline, type I procollagen, and total proteins. Fifty-four healthy smokers were
      studied during 10 days of smoking and again from days 10 to 20 following smoking
      cessation. After the first 10 days of abstinence they were randomized to double
      blind treatment with transdermal nicotine patches of 25 mg/day or placebo for a
      period of 10 days. During this period and during smoking, an expanded
      polytetrafluoroethylene tube was implanted into the subcutis. Following removal
      of the implant, total amino acids and peptides were extracted. Hydroxyproline and
      proline were analyzed by high-pressure liquid chromatography, type I procollagen
      was analyzed by enzyme-linked immunoassay, and total proteins were determined
      colorimetrically. In the 39 subjects who complied with the study protocol,
      abstinence from smoking did not affect the deposition of hydroxyproline, proline,
      type I procollagen, or total protein in the implants. During abstinence, the type
      I procollagen level increased by 18% in the transdermal nicotine patches group
      and decreased by 10% in the placebo group (p<0.05). We conclude that 20 days of
      abstinence from smoking does not affect collagen deposition in granulation
      tissue. However, in abstinent smokers, transdermal nicotine patches appears to
      increase type I collagen synthesis.

PMID- 16808803
TI  - Hyaluronan in human acute and chronic dermal wounds.
AB  - There is growing interest in the relationship of hyaluronan and inflammation in a
      number of physiologic processes including wound healing. The objective of this
      study was to make a quantitative comparison of inflammation and hyaluronan
      expression in human normal healing open wounds and in pressure ulcers. Using an
      open dermal wound model, myeloperoxidase activity was found to peak at day 3.
      Hyaluronan levels showed a bimodal distribution with transient peaks occurring on
      days 1 and 7. Mean levels of myeloperoxidase activity in pressure ulcers were
      significantly higher than at any time in the acute wounds, whereas hyaluronan
      levels were significantly lower than at any time in the acute wounds. Levels of
      hyaluronidase activity increased slightly in the postwound period. Hyaluronidase
      activity in pressure ulcers was significantly elevated compared with the acute
      wounds. These results suggest a role for increased enzymatic degradation of
      hyaluronan as a function of inflammation during wound repair. This is the first
      reported quantitative examination of hyaluronan expression in human acute dermal
      wounds and in chronic pressure ulcers.

PMID- 16808804
TI  - Cytokines and growth factors in wound drainage fluid from patients undergoing
      incisional hernia repair.
AB  - Knowing the dynamics of growth factor and cytokine secretion within the site of a
      surgical operation is important, as they play a crucial role in the
      pathophysiology of wound healing and are a target for modifying the repair
      response. The aim of this study was to evaluate the production of several
      cytokines and growth factors in the drainage wound fluid from patients undergoing
      incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1alpha, IL-1 ra,
      interferon-gamma, vascular endothelial growth factors and basic fibroblast growth
      factor. Ten female patients with abdominal midline incisional hernia undergoing
      surgical repair were included in this study. In all cases, a closed-suction drain
      was inserted in the wound below the fascia and removed on postoperative day 4.
      Wound fluid was collected on postoperative days 1-4 and the amount was recorded
      each time. Growth factors and cytokines production was evaluated as the whole
      amount produced over a 24-hour period. In all patients, the amount of drain fluid
      from surgical wounds was more copious the first day after surgery, it decreased
      significantly afterward. The presence of all cytokines was highest on
      postoperative day 1, decreasing over the following days. More specifically, the
      production of IL-1 ra, IL-6, IL-1alpha, and IL-10 on postoperative day 1 fell
      sharply on postoperative days 3 and 4, whereas, after an initial reduction,
      interferon-gamma showed an increase from day 2 onward. Vascular endothelial
      derived growth factor production increased progressively after the operation
      reaching statistical significance only on day 4. As for basic fibroblast growth
      factor, it showed an opposite pattern: it was higher on postoperative day 1
      decreasing thereafter. This analysis of cytokine and growth factor production in
      the drain fluid will lead us to a better evaluation of the events that follow a
      surgical wound and to a better understanding of the healing process.

PMID- 16808805
TI  - Scarless skin repair in immunodeficient mice.
AB  - Scarring, the end result of the wound healing process in adult mammals, is a
      problem of significant clinical importance. We observed that athymic nude-nu
      mice, similar to mammalian fetuses, are able to restore the structure and
      integrity of injured skin through a process resembling regeneration, where scar
      formation is absent. Among the postinjured skin tissues collected from athymic
      nude-nu, wild-type controls (C57BL/6J), severe-combined immunodeficient, Rag
      (lack of B and T cells), athymic (thymectomized neonates and adult C57BL/6J), and
      mice treated with an immunosuppressant (cyclosporin A), only athymic nude-nu mice
      showed: a lack of scar by histological examination (hematoxylin & eosin and
      Masson's trichrome staining), low levels of collagen (as determined by
      hydroxyproline content), high levels of hyaluronic acid, a statistically
      significant increase in elastic modulus for injured samples over unwounded
      (biomechanical testing) and low levels of the pro-scarring cytokines platelet
      derived growth factor-B and transforming growth factor beta1. Additionally,
      immunohistochemical and Western blot analyses of postinjured tissues as well as
      flow cytometry analysis of blood samples showed the presence of CD8-positive
      cells in all studied animals except nude-nu mice. We conclude that scarless skin
      healing in athymic nude-nu mice provides a new model to study the influence of
      the immune system on tissue regeneration.

PMID- 16808806
TI  - Time course analysis of hypoxia, granulation tissue and blood vessel growth, and
      remodeling in healing rat cutaneous incisional primary intention wounds.
AB  - Hypoxia and the development and remodeling of blood vessels and connective tissue
      in granulation tissue that forms in a wound gap following full-thickness skin
      incision in the rat were examined as a function of time. A 1.5 cm-long incisional
      wound was created in rat groin skin and the opposed edges sutured together.
      Wounds were harvested between 3 days and 16 weeks and hypoxia, percent vascular
      volume, cell proliferation and apoptosis, alpha-smooth muscle actin, vascular
      endothelial growth factor-A, vascular endothelial growth factor receptor-2, and
      transforming growth factor-beta1 expression in granulation tissue were then
      assessed. Hypoxia was evident between 3 and 7 days while maximal cell
      proliferation at 3 days (123.6+/-22.2 cells/mm2, p<0.001 when compared with
      normal skin) preceded the peak percent vascular volume that occurred at 7 days
      (15.83+/-1.10%, p<0.001 when compared with normal skin). The peak in cell
      apoptosis occurred at 3 weeks (12.1+/-1.3 cells/mm2, p<0.001 when compared with
      normal skin). Intense alpha-smooth muscle actin labeling in myofibroblasts was
      evident at 7 and 10 days. Vascular endothelial growth factor receptor-2 and
      vascular endothelial growth factor-A were detectable until 2 and 3 weeks,
      respectively, while transforming growth factor-beta1 protein was detectable in
      endothelial cells and myofibroblasts until 3-4 weeks and in the extracellular
      matrix for 16 weeks. Incisional wound granulation tissue largely developed within
      3-7 days in the presence of hypoxia. Remodeling, marked by a decline in the
      percent vascular volume and increased cellular apoptosis, occurred largely in the
      absence of detectable hypoxia. The expression of vascular endothelial growth
      factor-A, vascular endothelial growth factor receptor-2, and transforming growth
      factor-beta1 is evident prior, during, and after the peak of vascular volume
      reflecting multiple roles for these factors during wound healing.

PMID- 16808807
TI  - The alphavbeta6 integrin plays a role in compromised epidermal wound healing.
AB  - The alphavbeta6 integrin is an exclusively epithelial integrin that is highly
      expressed during fetal development. In adult tissue, alphavbeta6 integrin is
      expressed during inflammation, carcinogenesis, and in wound healing. We
      previously reported that alphavbeta6 integrin is highly expressed in poorly
      healing human wounds and its over-expression is associated with chronic wounds in
      a mouse model. The objective of this study was to investigate the role of
      alphavbeta6 integrin in compromised wound healing induced by hydrocortisone
      treatment or aging by using young and old mice deficient in or overexpressing the
      beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient
      (beta6-/-) animals showed a significant delay in wound healing when compared to
      their age-matched controls or younger beta6-/- mice. The most significant delay
      was observed at the stages where granulation tissue deposition was occurring.
      Hydrocortisone treatment significantly delayed wound healing in wild-type and
      beta6 integrin-deficient mice in comparison with the untreated controls. However,
      hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a
      significant delay in wound healing. The results of this study suggest that
      alphavbeta6 integrin plays an important role in wound healing in animals
      compromised by either age or stress mimicked by hydrocortisone.

PMID- 16808808
TI  - Expression of intracellular filament, collagen, and collagenase genes in diabetic
      and normal skin after injury.
AB  - Reports have shown differences in gene expression in the skin of diabetic and
      normal mice both at baseline and after injury. Cluster analysis identified
      distinct expression patterns within intermediate filaments and extracellular
      proteins. This report addresses the effect of diabetes and injury on the
      expression of keratin-associated proteins, keratin complexes, procollagen, and
      collagenase (matrix metalloproteinase; MMP) genes. At baseline keratin-associated
      proteins and keratin complexes gene expression was increased in diabetic mice.
      After surgery, the level of expression for keratin-associated proteins and
      keratin complexes genes decreased in diabetic mice, but did not change in normal
      mice. If the expression of a procollagen gene differed between diabetic and
      normal mice, the expression was lower in diabetic mice. Procollagen gene
      expression was elevated after skin excision compared with noninjured skin. At
      baseline, the level of MMP and tissue inhibitor of metalloproteinase gene
      expression was comparable between mouse strains. With injury, the expression of
      several MMP genes was increased in both mouse strains, but to higher levels in
      diabetic mice. At day 7, the level of MMP-9 activity in granulation tissue was
      elevated. This alteration may contribute to delayed healing in diabetic mice.
      Therefore, differences in gene expression exist between mouse strains and can
      assist in understanding of physiological manifestations, including delayed
      healing, in diabetic mice.

PMID- 16808809
TI  - The tetrapeptide acetyl-serine-aspartyl-lysine-proline improves skin flap
      survival and accelerates wound healing.
AB  - The tetrapeptide acetyl-serine-aspartyl-lysine-proline (AcSDKP) has recently been
      recognized as a potent angiogenic factor. Given the importance of vascular blood
      supply in the process of tissue repair we have investigated the ability of AcSDKP
      to contribute to the repair of cutaneous injuries by using dorsal and abdominal
      skin flap models. Postoperative subdermal AcSDKP injections (5
      microg/kg/injection twice a day for 3 days following flap elevation) prevented
      marginally perfused areas from undergoing necrosis. Mean skin survival area of
      abdominal and dorsal flaps ranged, respectively, from 50.9+/-19.3 and 53.4+/-4.2%
      in the control groups to 66.4+/-7.5 and 74.7+/-6.6% in AcSDKP-treated groups.
      Furthermore, in an ex vivo assay, AcSDKP applied locally to skin explants at
      doses from 10(-8) to 10(-5) M improved survival of the explanted skin exposed to
      UVB irradiation at 10 J/cm2. Increased reepithelialization, as well as higher
      levels of expression of basal keratin 14 and increased expression of fibronectin
      was observed after topical application of AcSDKP. These data provide experimental
      evidence that AcSDKP can improve the viability of ischemic skin flaps in the rat
      by promoting angiogenesis. Moreover, it enhances wound healing of injured
      avascular skin explants. Thus, these findings identify AcSDKP as a new tissue
      repair agent and suggest its potential clinical use for the management of skin
      wounds.

PMID- 16808810
TI  - Contraction of myofibroblasts in granulation tissue is dependent on Rho/Rho
      kinase/myosin light chain phosphatase activity.
AB  - During wound healing and fibrocontractive diseases fibroblasts acquire a smooth
      muscle cell-like phenotype by differentiating into contractile force generating
      myofibroblasts. We examined whether regulation of myofibroblast contraction in
      granulation tissue is dominated by Ca2+-induced phosphorylation of myosin light
      chain kinase or by Rho/Rho kinase (ROCK)-mediated inhibition of myosin light
      chain phosphatase, similar to that of cultured myofibroblasts. Strips of
      granulation tissue obtained from rat granuloma pouches were stimulated with
      endothelin-1 (ET-1), serotonin, and angiotensin-II and isometric force generation
      was measured. We here investigated ET-1 in depth, because it was the only agonist
      that produced a long-lasting and strong response. The ROCK inhibitor Y27632
      completely inhibited ET-1-promoted contraction and the phosphatase inhibitor
      calyculin elicited contraction in the absence of any other agonists, suggesting
      that activation of the Rho/ROCK/myosn light chain phosphatase pathway is critical
      in regulating in vivo myofibroblast contraction. Membrane depolarization with K+
      also stimulated a long-lasting contraction of granulation tissue; however, the
      amount of force generated was significantly less compared to ET-1. Moreover, K+
      induced contraction was inhibited by Y27632. These results are consistent with
      inhibition of myosin light chain phosphatase by the Rho/ROCK signaling pathway,
      which would account for the long-duration contraction of myofibroblasts necessary
      for wound closure.

PMID- 16808811
TI  - Lactate stimulates endothelial cell migration.
AB  - The significance of the high lactate levels that characterize healing wounds is
      not fully understood. Lactate has been shown to enhance collagen synthesis by
      fibroblasts and vascular endothelial growth factor (VEGF) production by
      macrophages and endothelial cells. VEGF has been shown to induce endothelial cell
      migration. However, it has not been shown whether accumulated lactate correlates
      with the biological activity of VEGF. Therefore, we investigated the effect of
      lactate on migration of endothelial cells. Human umbilical vein endothelial cells
      and human microvascular endothelial cells were cultured to subconfluent
      monolayers in standard six-well tissue culture plates. Following a 24-hour serum
      starvation, cells were treated with the indicated concentrations of l-lactate.
      Cell migration was assessed using a modified Boyden chamber. VEGF protein in the
      cell culture supernatant was measured by enzyme-linked immunoassay. Lactate
      enhanced VEGF protein synthesis in a time- and dose-dependent manner. Lactate
      added into the bottom well did not stimulate cellular migration from the upper
      well. However, lactate when added together with endothelial cells to the bottom
      well of the Boyden chamber increased cellular migration in a dose-dependent
      manner. This effect was blocked by anti-VEGF and by cycloheximide. Lactate
      enhances VEGF production in endothelial cells, although lactate, itself, is not a
      chemoattractant. We conclude that the lactate-mediated increase in cellular
      migration is regulated by VEGF.

PMID- 16808812
TI  - Enhanced wound-healing quality with bone marrow mesenchymal stem cells
      autografting after skin injury.
AB  - Adult stem cells exist in various tissues and organs and have the potential to
      differentiate into different cell lineages, including bone, cartilage, fat,
      tendon, muscle, and epithelial cells of the gastrointestinal tract. Here, we
      report that the in vitro expanded and purified bone marrow mesenchymal stem cells
      (MSCs) might take on phenotypes with characteristics of vascular endothelial
      cells (7% on day 3 and 15% on day 1) or epidermal cells (3% on day 3 and 13% on
      day 1) after being cultured under different lineage-specific culture conditions.
      Also, in vivo grafting experiments showed that 5-bromodeoxyuridine-labeled MSCs
      could convert into the phenotypes of vascular endothelial cells (3.43, 3.46, and
      2.94% on days 7, 14, and 28, respectively) in granulation tissues, sebaceous duct
      cells, and epidermal cells (0-1.49%) in regenerated skin, implying that these
      grafted MSCs might have transdifferentiated into the above three cell types.
      Animal autografting experiments with MSCs further confirmed that indices
      pertaining to wound healing quality, such as the speed of reepithelialization,
      the number of epidermal ridges and thickness of the regenerated epidermis, the
      morphology and the number and arrangement of microvasculature, fibroblasts and
      collagen, were much enhanced. Our results indicate that locally delivered bone
      marrow MSCs can enhance wound healing quality, and may generate de novo intact
      skin, resulting in perfect skin regeneration after full-thickness injury.

PMID- 16808813
TI  - Effect of recombinant human fibroblast growth factor-2 on intramuscular ectopic
      osteoinduction by recombinant human bone morphogenetic protein-2 in rats.
AB  - To clarify the effects of recombinant human fibroblast growth factor-2 (rhFGF-2)
      on the osteoconduction ability of recombinant human bone morphogenetic protein-2
      (rhBMP-2) in vivo, rhBMP-2 (2 microg) was mixed with different doses of rhFGF-2
      (0, 16, 80, 400, or 2,000 ng), and implanted into the lower leg muscle of rats
      using type I collagen as a carrier. Twenty-one days later, ectopic neoplastic
      bones had bone mineral content, bone area, and bone mineral density measured by
      means of dual energy X-ray absorptiometry and imaged by soft X-ray. The values
      for alkaline phosphatase activity and calcium content were determined, and
      histology obtained. In the group treated with rhFGF-2 at 16 ng, alkaline
      phosphatase activity, calcium content, bone mineral content, bone area, and bone
      mineral density were the greatest of all treatment groups, and the richest
      trabeculae were histologically observed in this group. In the groups treated with
      rhFGF-2 at 80, 400, or 2,000 ng, bone formation was suppressed in a dose
      dependent manner. These results indicate that rhFGF-2 promotes ectopic rhBMP-2
      related osteoinduction at a low concentration (16 ng) in vivo, and that it
      suppresses osteoinduction at a higher amount (>80 ng).

PMID- 16808815
TI  - Clinical assessment of infection in nonhealing ulcers analyzed by latent class
      analysis.
AB  - The distinction between bacterial colonization and infection relies on clinical
      judgement. Determining sensitivity and specificity of this judgement are
      problematic as no gold standard exists. Six specialists in wound management
      independently assessed 120 nonhealing chronic wounds. Sixty-five (54.2%) patients
      had venous ulcer, 18 (15%) arterial ulcers, 15 (12.5%) ulcerative pyoderma
      gangraenosum, 12 (10%) neuropathic or pressure ulcers, six (5%) vasculitis
      ulcers, and four patients had ulcers caused by a primary or metastatic cancer
      disease. Unrestricted latent class analysis was used for determining sensitivity
      and specificity in the observer's assessment of hypergranulation, redness, and
      overall impression of infection. Interrater agreement among observers was
      determined by restricted latent class analysis. The observers used the diagnoses
      (redness, hypergranulation, and overall impression of infection with different
      frequencies (p<0.001, Cochrane's Q test). A two latent class model fitted data.
      Sensitivity for hypergranulation ranged from 3 to 82%, for redness from 34 to 91%
      and for overall impression of infection from 37 to 90%. None of the observers
      were interchangeable. These results indicate that clinical assessment of chronic
      wounds for the presence of infection are difficult tasks accompanied by great
      variability and low reliability.

PMID- 16808814
TI  - Attenuation of cysteinyl leukotrienes induces human mesenchymal stem cell
      differentiation.
AB  - Although there are numerous investigations describing bone marrow cells or bone
      marrow derived cells at the site of such injuries as bone fractures, infarction
      and subsequent ischemic reperfusion injury, or cutaneous wounds, little is know
      about the factors that affect the cells in those clinical situations. Cysteinyl
      leukotrienes have been extensively investigated in airway diseases that may
      eventually lead to lung fibrosis; while the engraftment of mesenchymal stem cells
      have been shown to reverse bleomycin-induced lung fibrosis in vivo. Therefore, we
      elucidated the involvement of cysteinyl leukotrienes in human mesenchymal stem
      cell proliferation and differentiation. Human mesenchymal stem cells express the
      cysteinyl leukotriene type 1 receptor. Various doses of pranlukast, which is a
      specific cysteinyl leukotriene type 1 receptor antagonist, failed to affect the
      proliferation of cells; however, 10(-6) M of pranlukast significantly induced
      cellular cytoplasmic differentiation by showing microvilli sprouting and the
      emersion of rough endoplasmic reticulum within a 16-hour(s) incubation.
      Additionally, pranlukast-induced fibronectin protein production by human
      mesenchymal stem cells. Therefore, attenuation of the cysteinyl leukotriene
      pathway contributes to human mesenchymal stem cell differentiation and may
      contribute to modulation of the local injury site.

PMID- 16808816
TI  - Optimized delivery of skin keratinocytes by aerosolization and suspension in
      fibrin tissue adhesive.
AB  - Aerosolized suspensions of keratinocytes provide a potential therapy for wounds,
      but the effects of aerosolization on cell viability remain unclear. Likewise,
      little is known of the resulting cell distribution pattern and how this compares
      to the density required for epithelialization. The potential benefits of
      cospraying cells in the presence of fibrin adhesive are equally uncertain. Thus,
      in the present study we have optimized conditions for the aerosolization of
      cultured keratinocytes using a device (Tissomat) that supports the option for
      coapplication with fibrin (Tisseel). Cell viability was unaffected when sprayed
      at 10 psi, but a significant reduction in metabolic activity, as determined by
      the methylthiazoyldiphenol-tetrazolium assay, was observed at higher pressure.
      Bursts of 0.2 mL cell suspension (1.5x10(6)/mL) delivered from a height of 10 cm
      was sufficient to epithelialize an area of 10-15 cm2 within 7 days in vitro.
      Confluent areas corresponded to those with a density of 5,000-10,000 cells/cm2 at
      24 hours. Optimal cell growth in Tisseel was achieved through dilution of
      fibrinogen (1-3 mg/mL) and thrombin (2-5 IU/mL). This optimized formulation
      eliminated fluid run-off postspraying and stimulated a twofold increase in
      cellular response. Therefore, our in vitro data supports the theory that
      aerosolized suspensions of keratinocytes in fibrin will benefit healing.

PMID- 16808817
TI  - Measurement of optical properties to quantify healing of chronic diabetic wounds.
AB  - Measurement of scattering and absorption characteristics of tissue by near
      infrared spectroscopy may provide a clinically applicable, quantitative method of
      assessing healing of diabetic wounds. Twenty SICH-1 hairless rats were divided
      into a control group and a streptozotocin-induced diabetic group. Full-thickness
      wounds were made on the dorsal surface of each animal. Wounds were examined using
      a near infrared device with three wavelengths of incident light. Amplitude and
      phase of scattered light were obtained at four different source detector
      distances at each wavelength. The probe was positioned at six different
      locations. Tissue absorption and scattering coefficients were calculated from
      amplitude and phase data. Wound dimensions were calculated by cross and parallel
      polarization. Thirty-eight wounds were evaluated during the experiment. Wound
      size decreased at twice the rate in the control animals, whereas the average
      absorption coefficient was higher by a factor of two while the average value of
      the reduced scattering coefficient was 30% higher in the diabetic wounds. During
      healing, both scattering and absorption coefficients increased faster in the
      diabetics. Higher absorption in diabetic rats suggests impaired blood flow.
      Scattering may reflect tissue disorganization observed in delayed wound healing.
      We conclude that near infrared spectroscopy may differentiate between healing
      diabetic and nondiabetic wounds.

PMID- 16808819
TI  - Neuroimaging of focal cortical dysplasia.
AB  - Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy
      that is amenable to surgical resective treatment. The identification of
      structural FCD by magnetic resonance imaging (MRI) can contribute to the
      detection of the epileptogenic zone and improve the outcome of epilepsy surgery.
      MR epilepsy protocols that include specific T1 and T2 weighted, and fluid
      attenuated inversion recovery (FLAIR) sequences give complementary information
      about the characteristic imaging features of FCD; focal cortical thickening,
      blurring of the gray-white junction, high FLAIR signal, and gyral anatomical
      abnormalities. Novel imaging techniques such as magnetic resonance spectroscopy
      (MRS), magnetization transfer imaging (MTI), and diffusion tensor imaging (DTI)
      can improve the sensitivity of MR to localize the anatomical lesion.
      Functional/metabolic techniques such as positron emission tomography (PET), ictal
      subtraction single photon emission computed tomography (SPECT), functional MRI
      (fMRI), and magnetic source imaging (MSI) have the potential to visualize the
      metabolic, vascular, and epileptogenic properties of the FCD lesion,
      respectively. Identification of eloquent areas of cortex, to assist in the
      surgical resection plan, can be obtained non-invasively through the use of fMRI
      and MSI. Although a significant number of FCD lesions remain unidentified using
      current neuroimaging techniques, future advances should result in the
      identification of an increasing number of these cortical malformations.

PMID- 16808818
TI  - Effect of Vacuum-Assisted Closure Therapy on the expression of cytokines and
      proteases in wound fluid of adults with pressure ulcers.

PMID- 16808820
TI  - Neuroimaging of tuberculous myelitis: analysis of ten cases and review of
      literature.
AB  - We retrospectively reviewed the clinical and neuroimaging features of 10 patients
      with tuberculous myelitis. The most common presenting symptoms were fever (70%)
      and paraplegia (60%). Bladder and bowel symptoms were present in 90% patients. On
      MRI, the involvement of the cervical/thoracic segment of the spinal cord was most
      commonly seen (90%). The most consistent finding was hyperintense signals on T2
      weighted MRI. T1-weighted images showed isointense (n= 5) and hypointense (n= 4)
      signals in the spinal cord lesions. Post-contrast enhancement was present in 6
      patients, epidural enhancement in 4 patients, and cord swelling in 2 patients. We
      reviewed more than 250 published cases with the diagnosis of tuberculous myelitis
      and radiculomyelitis with special attention to MRI findings. It is predominantly
      a disease of the thoracic spinal cord. Most spinal cord lesions appear as
      hyperintense on T2 and iso- or hypointense on T1-weighted images. MRI findings in
      patients with spinal cord tuberculosis have both diagnostic and prognostic
      significance. Cord atrophy or cavitation and the presence of syrinx on MRI may be
      associated with poor outcome.

PMID- 16808821
TI  - Three-dimensional anisotropy contrast periodically rotated overlapping parallel
      lines with enhanced reconstruction (3DAC PROPELLER) on a 3.0T system: a new
      modality for routine clinical neuroimaging.
AB  - BACKGROUND: Clinical magnetic resonance imaging (MRI) has recently entered the
      "high-field" era, and systems equipped with 3.0-4.0T superconductive magnets are
      becoming the gold standard for diagnostic imaging. While higher signal-to-noise
      ratio (S/N) is a definite advantage of higher field systems, higher
      susceptibility effect remains to be a significant trade-off. To take advantage of
      a higher field system in performing routine clinical images of higher anatomical
      resolution, we implemented a vector contrast image technique to 3.0T imaging,
      three-dimensional anisotropy contrast (3DAC), with a PROPELLER (Periodically
      Rotated Overlapping Parallel Lines with Enhanced Reconstruction) sequence, a
      method capable of effectively eliminating undesired artifacts on rapid diffusion
      imaging sequences. METHODS: One hundred subjects (20 normal volunteers and 80
      volunteers with various central nervous system diseases) participated in the
      study. Anisotropic diffusion-weighted PROPELLER images were obtained on a General
      Electric (Waukesha, WI, USA) Signa 3.0T for each axis, with b-value of 1100
      sec/mm(2). Subsequently, 3DAC images were constructed using in-house software
      written on MATLAB (MathWorks, Natick, MA, USA). RESULTS: The vector contrast
      allows for providing exquisite anatomical detail illustrated by clear
      identification of all major tracts through the entire brain. 3DAC images provide
      better anatomical resolution for brainstem glioma than higher-resolution T2
      reversed images. Degenerative processes of disease-specific tracts were clearly
      identified as illustrated in cases of multiple system atrophy and Joseph-Machado
      disease. CONCLUSION: Anatomical images of significantly higher resolution than
      the best current standard, T2 reversed images, were successfully obtained. As a
      technique readily applicable under routine clinical setting, 3DAC PROPELLER on a
      3.0T system will be a powerful addition to diagnostic imaging.

PMID- 16808822
TI  - Carotid stent-supported angioplasty via radiobrachial route.
AB  - Endovascular stent-supported angioplasty is a treatment option for
      atherosclerotic disease of the cervical internal carotid artery in high-risk
      patients. The traditional transfemoral approach is not suitable for patients who
      suffer from common femoral artery or abdominal aorta atheropathy. We report a
      case of carotid stent deployment using the radial route in a 68-year-old man with
      type B aortic dissection, having severe right internal carotid artery origin
      stenosis, presenting with ipsilateral retinal ischemic events. Technical aspects
      of carotid stenting via the radial approach are described and the related
      literature is discussed.

PMID- 16808823
TI  - Intracranial angioplasty and stenting in the awake patient.
AB  - BACKGROUND AND PURPOSE: Endovascular treatment for intracranial atherosclerosis
      is evolving, but complications remain an issue. Most interventions are performed
      under general anesthesia, preventing intraprocedural clinical evaluations. We
      describe our approach to intracranial angioplasty and stenting, using local
      rather than general anesthesia, and intraprocedural neurological assessment.
      METHODS: We prospectively collected procedural and outcome information on all
      patients undergoing intracranial angioplasty and stenting. Patients underwent
      interventions under local anesthesia with mild intravenous sedation or analgesia
      only if needed. Intraoperative neurological evaluations were performed, and
      symptomatology was used to guide the interventional technique. RESULTS: Forty
      eight arteries in 40 patients with a mean age of 65.2 years were treated. Thirty
      two anterior and 16 posterior circulation segments were treated. Technical
      success was achieved in 100% of patients with reduction of the mean pretreatment
      stenosis from 85 +/- 8.6% to 7 +/- 10.1%. Stents were deployed in 40 segments;
      five patients were treated with drug-eluting stents. The cobalt-chromium coronary
      stents were the easiest to deliver. Thirty-seven patients were treated under
      local anesthesia and, of those, 61.4% experienced intraprocedural symptoms that
      led to some alteration of the interventional technique. Headache was the most
      common symptom, and, when persistent, it heralded the occurrence of subarachnoid
      hemorrhage. There were seven total neurological complications, but only five
      (10.5%) led to permanent morbidity (4 strokes) or mortality (1 death).
      CONCLUSIONS: Intracranial angioplasty and stenting can be successfully performed
      using coronary techniques and equipment including drug-eluting stents. Local
      anesthesia permits neurological evaluations and often leads to the adjustment of
      the interventional technique, potentially making the procedure safer.

PMID- 16808824
TI  - Mapping the relative contribution of gray matter activity vs. volume in brain
      PET: a new approach.
AB  - Interpretation of brain positron emission tomography (PET) in terms of function
      vs. structure is ambiguous owing to the partial volume effect (PVE). Therefore,
      observed differences in tracer distribution could reflect differences in either
      activity or volume, a problem that applies principally to gray matter (GM) since
      white matter (WM) virtually always has uniform activity. To assess the
      contribution of GM volume vs. activity, we implemented a method to directly
      compare PET images with underlying structure, and applied it to resting-state
      (18)Fluoro-deoxy-glucose-PET (FDG) of healthy subjects. Methods. Average GM and
      WM PVE-corrected mean FDG uptake values were applied onto co-registered segmented
      magnetic resonance imaging data sets to generate a "virtual PET" in which
      activity is proportional to GM volume and resolution set to that of PET. The raw
      PET and virtual PET values were then compared across the sample of subjects,
      first voxel-wise to detect clusters with significant activity-volume mismatch,
      and second within regions-of-interest (ROI) to quantify mismatches between
      unsmoothed voxel values. Results. Relative to volume, there was significant
      hyperactivity of most GM structures of the dorsal brain-except the thalamus-and
      significant hypoactivity of the temporal lobe, hippocampal region, and
      cerebellum, consistent across the voxel- and ROI-based analyses. Conclusion. As
      applied to normals, our method documented the expected contribution of functional
      activity independently of local differences in GM volume in the normal pattern of
      FDG uptake, and disclosed marked heterogeneities in functional activity per unit
      GM volume among structures. This generic method should find applications in
      pathological states as well as for other PET and SPECT radiotracers.

PMID- 16808825
TI  - Hematoma size in deep intracerebral hemorrhage and its correlation with dot-like
      hemosiderin spots on gradient echo T2*-weighted MRI.
AB  - BACKGROUND AND PURPOSE: Dot-like low intensity spots (dot-like hemosiderin spots:
      dotHSs) on gradient echo T2*-weighted MRI have been histologically diagnosed to
      represent old cerebral microbleeds associated with microangiopathies. They have
      also been correlated to the fragility of small vessels and the tendency to bleed.
      Therefore, a substantial number of dotHSs might be associated with a large-sized,
      deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old
      microbleeds that did not enlarge to symptomatic size. METHODS: To investigate how
      dotHSs are related to the size (maximal diameter) of primary deep ICH, we
      analyzed the diameter and the number of dotHSs in 151 patients with deep ICH not
      associated with subarachnoid hemorrhage or intraventricular hemorrhage (75 males
      and 76 females, age ranged from 37 to 90 [65.7 +/- 11.3 years old] who were
      consecutively admitted to Hakodate Municipal Hospital. The hazard ratio (HR) for
      a maximal diameter of deep ICH < or =2 cm was estimated, using the number of
      dotHSs and risk factors for stroke. RESULTS: The number of dotHSs associated with
      the diameter < or =2 cm was 9.2 +/- 11.5, significantly larger than that with the
      diameter > or =2 cm (4.7 +/- 7.0, P= .012). Multivariate analysis revealed that a
      maximal diameter of deep ICH of < or =2 cm was found in patients with dotHS (HR,
      3.7; 95% confidence interval [CI], 1.4-10.1; P= .009). CONCLUSION: Though small
      sample size limited the power of our analyses, these findings suggest that the
      number of dotHSs may be associated with a small diameter of deep ICH.

PMID- 16808826
TI  - Prevalence of white matter hyperintensities in a young healthy population.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are bright objects
      observed in the white matter on brain magnetic resonance (MR) imaging. WMHs are
      often reported as "normal" findings but may represent pathological changes. The
      prevalence of WMHs appears to increase with increasing age although both the
      typical timing and clinical significance of their appearance among medically and
      neurologically healthy persons remains unclear. We assessed the prevalence of
      WMHs in a cohort of younger healthy subjects. METHODS: Our study comprised 243
      healthy subjects ages 16-65 years from our prospective normative MR imaging
      database. MR scans were rated for presence of periventricular and centrum
      semiovale WMHs using a four-point visual semi-quantitative scale. RESULTS: WMHs
      occurred in 5.3% (13 of 243) of subjects. All WMHs were small (rating of 0.5)
      except one subject age 65 years who had large WMHs (ratings of 2). The median age
      for subjects with no WMHs was 34.5 years compared to 57.0 years for subjects with
      WMHs. There were no gender differences (P= .76). Older age correlated with
      presence of WMHs (r = 0.24; P= .01). Age greater than 55 years had a 10-fold
      increase in the prevalence of WMHs compared to age < or =55 years (odds ratio =
      10.01; 95% confidence interval = 3.1-32.3; P < .001). CONCLUSION: WMHs were
      uncommon in a younger healthy population screened for comorbid diseases, but
      increased 10-fold in subjects over 55 years of age. When present, the WMHs are
      generally small (rating of 0.5). While large WMHs appear to be associated with
      cognitive deterioration, the optimum threshold for identification, clinical
      significance, and prognostic value of smaller white matter changes requires
      further research.

PMID- 16808827
TI  - Screening for high-grade carotid stenosis using a portable ultrasonography
      instrument.
AB  - BACKGROUND AND PURPOSE: We investigated the diagnostic performance of a brief
      Power Doppler Imaging (PDI) screening examination for carotid artery stenoses
      using a newly developed portable instrument. METHODS: A highly experienced
      sonographer screened in total 152 carotid arteries by either continuous wave (cw)
      Doppler (n= 50) or a lightweight (2.4 kg) portable duplex device (n= 102) in a
      prospective study of 76 high-risk patients. The screening protocols included
      either spectrum analysis and frequency shift measurement in both internal carotid
      arteries with cw-Doppler or determination of area and diameter ratios in
      transverse and longitudinal views of both carotid arteries in B-mode and with
      PDI, but without velocity measurement. Both protocols were evaluated against a
      complete routine duplex ultrasonography examination. RESULTS: According to the
      complete examination, stenoses were <50% in 73 of 102 (71.6%), 50-75% in 19 of
      102 (18.6%), 75-95% in 7 of 102 (6.9%), and occluded in 3 of 102 (2.9%) arteries
      (PDI cohort), and <50% in 39 of 50 (78%), 50-75% in 8 of 50 (16%), 75-95% in 2 of
      50 (4%), and occluded in 1 of 50 (2%) artery (cw-Doppler cohort). Mean screening
      time was 8.8 +/- 2.5 minute (PDI) and 9.4 +/- 2.6 minute (cw-Doppler). For
      stenoses >75%, A(z) values (area under the receiver operating characteristics
      curve) were 0.897 for area ratios, 0.843 for diameter ratios (PDI protocol) and
      1.0 for the cw-Doppler protocol. CONCLUSIONS: The diagnostic performance of the
      cw-Doppler protocol was superior to the PDI protocol. Nevertheless, both
      protocols appear suitable as inexpensive screening strategies to identify
      subjects with >75% stenosis measured by carotid Doppler ultrasound. However,
      these preliminary data need further verification.

PMID- 16808828
TI  - T2-weighted and T2 relaxometry images in patients with medial temporal lobe
      epilepsy.
AB  - PURPOSE: Quantification of increased T2-weighted MRI signal that is associated
      with hippocampal sclerosis (HS) can be performed through (1) mean of hippocampal
      signal in single-echo T2 MRI and (2) hippocampal T2 relaxometry. It is not clear
      whether these two techniques are equivalent. In this study, we compare the
      hippocampal signal, detected by single-echo T2 quantification and by T2
      relaxometry, in patients with medial temporal lobe epilepsy (MTLE). METHODS: We
      studied magnetic resonance images from 50 MTLE patients and 15 healthy subjects.
      We compared the quantification of a T2 signal from single echo images to T2
      relaxometry, both obtained from a manually traced region of interest (ROI) in
      coronal slices involving the whole hippocampus. Repeated measures ANOVA was used
      to evaluate the differences in the distribution of the Z-scores from single-echo
      T2 quantification and T2 relaxometry within subjects. RESULTS: We observed a
      significant difference between the measurements obtained from single-echo T2
      quantification and T2 relaxometry (P < .001). Measurements from head, body, and
      tail of the hippocampus were different (P=.04), with a significant interaction
      between anatomic location and type of measurement used (P= .008). Post hoc paired
      comparisons revealed that T2 relaxometry yielded greater Z-scores for the body
      (P= .002) and tail (P < .0001). CONCLUSIONS: For each subject with MTLE, T2
      relaxometry was able to detect a higher signal in the body and tail of the
      hippocampus compared to single-echo T2. This is a possible indicator that T2
      relaxometry is more sensitive in detecting T2 abnormalities within the body and
      tail of the hippocampus in patients with MTLE.

PMID- 16808829
TI  - Topographic patterns of small subcortical infarcts associated with MCA stenosis:
      a diffusion-weighted MRI study.
AB  - BACKGROUND AND PURPOSE: Small subcortical infarcts (SSI, maximum lesion diameter
      < or =2.0 cm) are usually considered as infarcts caused by small vessel disease.
      However, SSI can also be associated with large artery occlusive disease such as
      middle cerebral artery (MCA) stenosis. We performed a prospective study to
      investigate the relationship between MCA stenosis and SSI distribution and
      further to investigate the mechanism of SSI caused by MCA stenosis. METHODS:
      Magnetic resonance angiography (MRA) and diffusion-weighed MRI (DWI) of
      consecutive acute ischemic stroke patients with recent SSI were studied. The
      distribution of acute infarcts on DWI was categorized as cortical infarct (CI),
      border zone infarct (BI), or perforating artery infarct (PAI). RESULTS: Totally,
      93 cases were recruited, among which 12 had single SSI with MCA stenosis (group
      1) and 26 patients had multiple SSI with MCA stenosis (group 2), while 55
      patients without MCA stenosis had single SSI (group 3). For patients with single
      SSI and MCA stenosis, 6 had BI and 6 had PAI; for patients with multiple SSI and
      MCA stenosis, 25 had BI, 4 had PAI and 9 had CI (compared with group 1: P= .001);
      for patients with single SSI but without MCA stenosis, 20 had BI and 35 had PAI
      (compared with group 1: P= .58). CONCLUSION: Multiple acute infarcts along the
      border zone are the commonest pattern in small infarcts with MCA stenosis,
      especially among those with multiple acute infarcts. Our data suggest that
      hemodynamic compromise and artery-to-artery embolism may be both important
      factors for infarcts in patients with MCA stenosis.

PMID- 16808830
TI  - Imaging cerebral activity in recovery from chronic traumatic brain injury: a
      preliminary report.
AB  - People in chronic phase of traumatic brain injury (TBI) are often told that there
      will be no further recovery in brain function, that they are in a "static phase."
      Holistic Approach to NeuroDevelopment and Learning Efficiency (HANDLE), an
      alternative therapy, aims to improve function by teaching a series of physical
      and mental activities that clients perform and encouraging changes in lifestyle.
      Five subjects (3 males) with chronic TBI (at least 3 years since ictus) completed
      the HANDLE Institute's program and were prospectively evaluated. Each had six
      regional cerebral blood flow (rCBF) single-photon emission computed tomography
      (SPECT) scans over 7 months (scans n= 30). Paired scans were performed with
      injection of Tc-99m ECD to image rCBF at rest and during the HANDLE "Crossed Arm
      Bounce" (CAB) exercise before the program, at 3-4 months into the program, and at
      6-7 months, after the program had ended. SPECT images were analyzed statistically
      using Neurostat in which image sets were coregistered and warped into Talaraich
      atlas for pairwise subtraction between conditions. Group analysis of SPECT showed
      that CAB activated (increased rCBF) vermis and cerebellar hemispheres in first
      two paired scans and anterior cingulate and vermis on the final pair. Increased
      rCBF at rest occurred in cerebellar hemispheres, vermis, and right dorsomedial
      frontal cortex. These preliminary observations suggest that there may be a role
      of the hindbrain (vermis and cerebellum) with HANDLE treatment of chronic TBI.

PMID- 16808831
TI  - Transcranial doppler and carotid duplex ultrasonography findings in Bow hunter's
      syndrome.
AB  - Bow hunter's syndrome (BHS) is caused by transient vertebro-basilar ischemia on
      head rotation. We report a patient with BHS who was identified from dynamic
      changes to blood flow velocities in the posterior cerebral, basilar and vertebral
      arteries using carotid duplex ultrasonography and transcranial Doppler,
      simultaneously. Neurosonology appears to be useful for diagnosing and evaluating
      BHS.

PMID- 16808832
TI  - Diffusion tensor imaging and fiber-tracking in Marchiafava-Bignami disease.
AB  - Marchiafava-Bignami disease, a rare disorder most commonly seen in patients with
      a history of alcohol consumption, involves demyelination and subsequent necrosis
      of the corpus callosum. Diffusion tensor imaging demonstrates regional
      abnormalities in the corpus callosum that are not evident by conventional
      magnetic resonance imaging (MRI). Furthermore, fiber-tracking demonstrates
      significant disruption of axonal fiber bundles within the corpus callosum, most
      marked within the body, corresponding to the clinical finding of interhemispheric
      disconnection, which is characteristic of the disease.

PMID- 16808833
TI  - Neuroimaging findings in neurosyphilis.
AB  - We report two cases of neurosyphilis with atypical clinical presentations that
      were compounded by atypical neuroimaging findings. In the first case, MRI brain
      scan findings were felt to be compatible with mesial temporal sclerosis or herpes
      simplex encephalitis. The second patient presented with a clinical picture
      compatible with normal pressure hydrocephalus as well as some degree of
      ventricular enlargement and prominent periventricular white matter changes by MRI
      brain scan. He actually underwent ventriculo-peritoneal shunting prior to
      determination that he had active syphilitic involvement of the central nervous
      system. Neurosyphilis, "the great imitator," is not only capable of mimicking
      various other neurological disease clinical presentations, it can also mimic
      neuroimaging features of various other disease processes as well.

PMID- 16808834
TI  - P-value based visualization of codon usage data.
AB  - Two important and not yet solved problems in bacterial genome research are the
      identification of horizontally transferred genes and the prediction of gene
      expression levels. Both problems can be addressed by multivariate analysis of
      codon usage data. In particular dimensionality reduction methods for
      visualization of multivariate data have shown to be effective tools for codon
      usage analysis. We here propose a multidimensional scaling approach using a novel
      similarity measure for codon usage tables. Our probabilistic similarity measure
      is based on P-values derived from the well-known chi-square test for comparison
      of two distributions. Experimental results on four microbial genomes indicate
      that the new method is well-suited for the analysis of horizontal gene transfer
      and translational selection. As compared with the widely-used correspondence
      analysis, our method did not suffer from outlier sensitivity and showed a better
      clustering of putative alien genes in most cases.

PMID- 16808835
TI  - A critical review of mathematical models and data used in diabetology.
AB  - The literature dealing with mathematical modelling for diabetes is abundant.
      During the last decades, a variety of models have been devoted to different
      aspects of diabetes, including glucose and insulin dynamics, management and
      complications prevention, cost and cost-effectiveness of strategies and
      epidemiology of diabetes in general. Several reviews are published regularly on
      mathematical models used for specific aspects of diabetes. In the present paper
      we propose a global overview of mathematical models dealing with many aspects of
      diabetes and using various tools. The review includes, side by side, models which
      are simple and/or comprehensive; deterministic and/or stochastic; continuous
      and/or discrete; using ordinary differential equations, partial differential
      equations, optimal control theory, integral equations, matrix analysis and
      computer algorithms.

PMID- 16808836
TI  - In vitro hydrodynamic properties of the Miethke ProGAV hydrocephalus shunt.
AB  - BACKGROUND: Adjustable shunts are very popular in the management of hydrocephalus
      and are believed to help in minimizing the number of surgical revisions. The
      drawback with almost all constructions is that they may be accidentally
      readjusted in relatively weak magnetic fields (around 30-40 mTesla) MATERIALS AND
      METHODS: The ProGav Miethke shunt is composed of an adjustable balloon-spring
      valve unit and an integrated over-drainage compensating gravitational device
      (known as the shunt assistant). A mechanical 'brake' is intended to prevent
      changes to the valve's performance level in a strong magnetic field. We evaluated
      the performance and hydrodynamic properties of a sample of three valves in the UK
      Shunt Evaluation Laboratory. RESULTS: All the shunts showed good mechanical
      durability over the three-month period of testing, and good stability of
      hydrodynamic performance over a one-month period. The pressure-flow performance
      curves, operating, opening and closing pressures fell within the limits specified
      by the manufacturer, and changed according to the programmed performance levels.
      The operating pressure increased when the shunt assistant was in the vertical
      position, as specified. The valve has a low hydrodynamic resistance (0.53 mm mmHg
      ml(-1) min(-1)). External programming proved to be easy and reliable. Strong
      magnetic fields from a 3 Tesla MR scanner were not able to change the programming
      of the valve. CONCLUSION: The ProGAV shunt is an adjustable, low resistance valve
      that is able to limit posture-related over-drainage. Unlike other adjustable
      valves, the ProGAV cannot be accidentally re-adjusted by external magnetic field
      such as a 3T MR scanner.

PMID- 16808838
TI  - Inequalities in health: a comparative study between ethnic Norwegians and
      Pakistanis in Oslo, Norway.
AB  - BACKGROUND: The objective of the study was to observe the inequality in health
      from the perspective of socio-economic factors in relation to ethnic Pakistanis
      and ethnic Norwegians in Oslo, Norway. METHOD: Data was collected by using an
      open and structured questionnaire, as a part of the Oslo Health Study 2000-2001.
      Accordingly 13581 ethnic Norwegians (45% of the eligible) participated as against
      339 ethnic Pakistanis (38% of the eligible). RESULTS: The ethnic Pakistanis
      reported a higher prevalence of poor self-rated health 54.7% as opposed to 22.1%
      (p < 0.001) in ethnic Norwegians, 14% vs. 2.6% (p < 0.001) in diabetes, and 22.0%
      vs. 9.9% (p < 0.001) in psychological distress. The socio-economic conditions
      were inversely related to self-rated health, diabetes and distress for the ethnic
      Norwegians. However, this was surprisingly not the case for the ethnic
      Pakistanis. Odd ratios did not interfere with the occurrence of diabetes, even
      after adjusting all the markers of socio-economic status in the multivariate
      model, while self-reported health and distress showed moderate reduction in the
      risk estimation. CONCLUSION: There is a large diversity of self-rated health,
      prevalence of diabetes and distress among the ethnic Pakistanis and Norwegians.
      Socio-economic status may partly explain the observed inequalities in health.
      Uncontrolled variables like genetics, lifestyle factors and psychosocial factors
      related to migration such as social support, community participation,
      discrimination, and integration may have contributed to the observed phenomenon.
      This may underline the importance of a multidisciplinary approach in future
      studies.

PMID- 16808837
TI  - Wnt expression and canonical Wnt signaling in human bone marrow B lymphopoiesis.
AB  - BACKGROUND: The early B lymphopoiesis in mammals is regulated through close
      interactions with stromal cells and components of the intracellular matrix in the
      bone marrow (BM) microenvironment. Although B lymphopoiesis has been studied for
      decades, the factors that are implicated in this process, both autocrine and
      paracrine, are inadequately explored. Wnt signaling is known to be involved in
      embryonic development and growth regulation of tissues and cancer. Wnt molecules
      are produced in the BM, and we here ask whether canonical Wnt signaling has a
      role in regulating human BM B lymphopoiesis. RESULTS: Examination of the mRNA
      expression pattern of Wnt ligands, Fzd receptors and Wnt antagonists revealed
      that BM B progenitor cells and stromal cells express a set of ligands and
      receptors available for induction of Wnt signaling as well as antagonists for
      fine tuning of this signaling. Furthermore, different B progenitor maturation
      stages showed differential expression of Wnt receptors and co-receptors, beta
      catenin, plakoglobin, LEF-1 and TCF-4 mRNAs, suggesting canonical Wnt signaling
      as a regulator of early B lymphopoiesis. Exogenous Wnt3A induced stabilization
      and nuclear accumulation of beta-catenin in primary lineage restricted B
      progenitor cells. Also, Wnt3A inhibited B lymphopoiesis of CD133+CD10-
      hematopoietic progenitor cells and CD10+ B progenitor cells in coculture assays
      using a supportive layer of stromal cells. This effect was blocked by the Wnt
      antagonists sFRP1 or Dkk1. Examination of early events in the coculture showed
      that Wnt3A inhibits cell division of B progenitor cells. CONCLUSION: These
      results indicate that canonical Wnt signaling is involved in human BM B
      lymphopoiesis where it acts as a negative regulator of cell proliferation in a
      direct or stroma dependent manner.

PMID- 16808839
TI  - Dyspnea assessment and adverse events during sputum induction in COPD.
AB  - BACKGROUND: The inhalation of normal or hypertonic saline during sputum induction
      (SI) may act as an indirect bronchoconstrictive stimulus leading to dyspnea and
      lung function deterioration. Our aim was to assess dyspnea and adverse events in
      COPD patients who undergo SI following a safety protocol. METHODS: Sputum was
      induced by normal and hypertonic (4.5%) saline solution in 65 patients with COPD
      of varying severity. In order to minimize saline-induced bronchoconstriction a
      protocol based on the European Respiratory Society sputum induction Task group
      report was followed. Dyspnea change was scored using the Borg scale and lung
      function was assessed by spirometry and oximetry. RESULTS: Borg score changes
      [median(IQR) 1.5(0-2)] were observed during SI in 40 subjects; 16 patients
      required temporary discontinuation of the procedure due to dyspnea-general
      discomfort and 2 did not complete the session due to dyspnea-wheezing. The change
      in Borg dyspnea score was significantly correlated with oxygen saturation and
      heart rate changes and with discontinuation of the procedure due to undesired
      symptoms. 19 subjects presented an hyperresponsive reaction (decline>20% from
      baseline FEV1). No significant correlation between Borg changes and FEV1 decline
      was found. Patients with advanced COPD presented significantly greater Borg and
      oxygen saturation changes than patients with less severe disease (p = 0.02 and p
      = 0.001, respectively). Baseline FEV1, oxygen saturation and 6MWT demonstrated
      significant diagnostic values in distinguishing subjects who develop an adverse
      physiologic reaction during the procedure. CONCLUSION: COPD patients undergoing
      SI following a safety protocol do not experience major adverse events. Dyspnea
      and oxygen desaturation is more likely to occur in patients with disease in
      advanced stages, leading to short discontinuation or less frequently to
      termination of the procedure. Baseline FEV1, oxygen saturation and 6MWT may have
      a prognostic value for the development of these adverse events and might be
      useful to be evaluated in advance.

PMID- 16808840
TI  - Support for a rare pattern of temperature-dependent sex determination in archaic
      reptiles: evidence from two species of tuatara (Sphenodon).
AB  - BACKGROUND: The sex of many reptiles is determined by the temperature an embryo
      experiences during its development. Three patterns of temperature-dependent sex
      determination (TSD) have been defined, but one pattern where only males are
      produced above an upper temperature threshold (Type IB) is controversial. Here we
      report new data on the relationship between constant temperature incubation and
      sexual phenotype in two species of tuatara (Sphenodon), archaic reptiles of
      enormous zoological significance as the sole representatives of a once widespread
      reptilian order. RESULTS: In both species, the pattern observed with constant
      incubation temperatures from 18 to 23 degrees C (or 24 degrees C) supported a
      female-->male (FM or Type IB) pattern of TSD: in Sphenodon guntheri males were
      produced above a pivotal temperature of 21.6 degrees C, and in S. punctatus
      (unnamed subspecies on Stephens Island, Cook Strait), males were produced above a
      pivotal temperature of 22.0 degrees C. The pivotal temperatures and scaling
      parameters differed between species (p < 0.001). The thermosensitive period
      (TSP), where temperature influences gonad morphogenesis, occurs between 0.25 and
      0.55 of embryonic development. While it is possible that the more common female-
      >male-->female (FMF or Type II) pattern exists, with a second pivotal temperature
      above 23-24 degrees C, we review several lines of evidence to the contrary. Most
      notably, we show that in S. punctatus, the warmest natural nests during the TSP
      produce predominantly males. CONCLUSION: An FM pattern of TSD could be currently
      adaptive in promoting sexual size dimorphism in tuatara. However, an FM pattern
      has particularly serious consequences for S. guntheri because current patterns of
      global warming could exacerbate the male bias already present in the relic
      population.

PMID- 16808841
TI  - A maximum likelihood framework for protein design.
AB  - BACKGROUND: The aim of protein design is to predict amino-acid sequences
      compatible with a given target structure. Traditionally envisioned as a purely
      thermodynamic question, this problem can also be understood in a wider context,
      where additional constraints are captured by learning the sequence patterns
      displayed by natural proteins of known conformation. In this latter perspective,
      however, we still need a theoretical formalization of the question, leading to
      general and efficient learning methods, and allowing for the selection of fast
      and accurate objective functions quantifying sequence/structure compatibility.
      RESULTS: We propose a formulation of the protein design problem in terms of model
      based statistical inference. Our framework uses the maximum likelihood principle
      to optimize the unknown parameters of a statistical potential, which we call an
      inverse potential to contrast with classical potentials used for structure
      prediction. We propose an implementation based on Markov chain Monte Carlo, in
      which the likelihood is maximized by gradient descent and is numerically
      estimated by thermodynamic integration. The fit of the models is evaluated by
      cross-validation. We apply this to a simple pairwise contact potential,
      supplemented with a solvent-accessibility term, and show that the resulting
      models have a better predictive power than currently available pairwise
      potentials. Furthermore, the model comparison method presented here allows one to
      measure the relative contribution of each component of the potential, and to
      choose the optimal number of accessibility classes, which turns out to be much
      higher than classically considered. CONCLUSION: Altogether, this reformulation
      makes it possible to test a wide diversity of models, using different forms of
      potentials, or accounting for other factors than just the constraint of
      thermodynamic stability. Ultimately, such model-based statistical analyses may
      help to understand the forces shaping protein sequences, and driving their
      evolution.

PMID- 16808842
TI  - Measuring the impact and distress of health problems from the individual's
      perspective: development of the Perceived Impact of Problem Profile (PIPP).
AB  - BACKGROUND: The aim of this study was to develop and conduct preliminary
      validation of the Perceived Impact of Problem Profile (PIPP). Based on the
      biopsychosocial model of health and functioning, the PIPP was intended as a
      generic research and clinical measurement tool to assess the impact and distress
      of health conditions from the individuals' perspective. The ICF classification
      system was used to guide the structure of the PIPP with subscales included to
      assess impact on self-care, mobility, participation, relationships and
      psychological well-being. While the ICF focuses on the classification of
      objective health and health related status, the PIPP broadens this focus to
      address the individuals' subjective experience of their health condition.
      METHODS: An item pool of 23 items assessing both impact and distress on five key
      domains was generated. These were administered to 169 adults with mobility
      impairment. Rasch analysis using RUMM2020 was conducted to assess the
      psychometric properties of each set of items. Preliminary construct validation of
      the PIPP was performed using the EQ5D. RESULTS: For both the Impact and Distress
      scales of the PIPP, the five subscales (Self-care, Mobility, Participation,
      Relationships, and Psychological Well-being) showed adequate psychometric
      properties, demonstrating fit to the Rasch model. All subscales showed adequate
      person separation reliability and no evidence of differential item functioning
      for sex, age, educational level or rural vs urban residence. Preliminary validity
      testing using the EQ5D items provided support for the subscales. CONCLUSION: This
      preliminary study, using a sample of adults with mobility impairment, provides
      support for the psychometric properties of the PIPP as a potential clinical and
      research measurement tool. The PIPP provides a brief, but comprehensive means to
      assess the key ICF components, focusing on the individuals' perspective of the
      impact and distress caused by their health condition. Further validation of its
      use across different health conditions and varying cultural settings is required.

PMID- 16808843
TI  - Hypoxic vasoconstriction of partial muscular intra-acinar pulmonary arteries in
      murine precision cut lung slices.
AB  - BACKGROUND: Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV) which
      serves to match lung perfusion to ventilation. The underlying mechanisms are not
      fully resolved yet. The major vascular segment contributing to HPV, the intra
      acinar artery, is mostly located in that part of the lung that cannot be
      selectively reached by the presently available techniques, e.g. hemodynamic
      studies of isolated perfused lungs, recordings from dissected proximal arterial
      segments or analysis of subpleural vessels. The aim of the present study was to
      establish a model which allows the investigation of HPV and its underlying
      mechanisms in small intra-acinar arteries. METHODS: Intra-acinar arteries of the
      mouse lung were studied in 200 mum thick precision-cut lung slices (PCLS). The
      organisation of the muscle coat of these vessels was characterized by alpha
      smooth muscle actin immunohistochemistry. Basic features of intra-acinar HPV were
      characterized, and then the impact of reactive oxygen species (ROS) scavengers,
      inhibitors of the respiratory chain and Krebs cycle metabolites was analysed.
      RESULTS: Intra-acinar arteries are equipped with a discontinuous spiral of alpha
      smooth muscle actin-immunoreactive cells. They exhibit a monophasic HPV (medium
      gassed with 1% O2) that started to fade after 40 min and was lost after 80 min.
      This HPV, but not vasoconstriction induced by the thromboxane analogue U46619,
      was effectively blocked by nitro blue tetrazolium and diphenyleniodonium,
      indicating the involvement of ROS and flavoproteins. Inhibition of mitochondrial
      complexes II (3-nitropropionic acid, thenoyltrifluoroacetone) and III (antimycin
      A) specifically interfered with HPV, whereas blockade of complex IV (sodium
      azide) unspecifically inhibited both HPV and U46619-induced constriction.
      Succinate blocked HPV whereas fumarate had minor effects on vasoconstriction.
      CONCLUSION: This study establishes the first model for investigation of basic
      characteristics of HPV directly in intra-acinar murine pulmonary vessels. The
      data are consistent with a critical involvement of ROS, flavoproteins, and of
      mitochondrial complexes II and III in intra-acinar HPV. In view of the lack of
      specificity of any of the classical inhibitors used in such types of experiments,
      validation awaits the use of appropriate knockout strains and siRNA interference,
      for which the present model represents a well-suited approach.

PMID- 16808844
TI  - Correlation of symptom clusters of schizophrenia with absolute powers of main
      frequency bands in quantitative EEG.
AB  - BACKGROUND: Research of QEEG activity power spectra has shown intriguing results
      in patients with schizophrenia. Different symptom clusters have been correlated
      to QEEG frequency bands. The findings have been to some extent inconsistent.
      Replication of the findings of previous research is thus an important task. In
      the current study we investigated the correlations between the absolute powers of
      delta, theta, alpha, and beta frequency bands over the fronto-central scalp area
      (FC) with the PANSS subscales and the Liddle's factors in 16 patients with
      schizophrenia.The authors hypothesised a priori the correlations reported by
      Harris et al (1999) of PANSS negative subscale with delta power, Liddle's
      psychomotor poverty with delta and beta powers, disorganisation with delta power
      and reality distortion with alpha power on the midline FC. METHODS: The sample
      consisted of 16 patients with chronic schizophrenia considered as having
      insufficient clinical response to conventional antipsychotic treatment and
      evidencing a relapse. The correlations between quantitative
      electroencephalography (QEEG) absolute powers of delta (1.5-3.0 Hz), theta (3.0
      7.5 Hz), alpha (7.5-12.5 Hz), and beta (12.5-20.0 Hz) frequency bands over the
      fronto-central scalp area (FC) with PANSS subscales and Liddle's factors (reality
      distortion, disorganisation, psychomotor poverty) were investigated. RESULTS:
      Significant positive correlations were found between the beta and psychomotor
      poverty (p < 0.05). Trends towards positive correlations (p < 0.1) were observed
      between delta and PANSS negative subscale and psychomotor poverty. Alpha did not
      correlate with reality distortion and delta did not correlate with
      disorganisation.Post hoc analysis revealed correlations of the same magnitude
      between beta and psychopathology generally over FC. CONCLUSION: The a priori
      hypothesis was partly supported by the correlation of the beta and psychomotor
      poverty. Liddle's factors showed correlations of the same magnitude with PANSS
      subscales. Supplementary analysis showed beta frequency correlating non
      specifically over FC with a wide range of psychiatric symptomatology in patients
      with schizophrenia having a relapse.

PMID- 16808845
TI  - A novel system for gene silencing using siRNAs in rice leaf and stem-derived
      protoplasts.
AB  - BACKGROUND: Transient assays using protoplasts are ideal for processing large
      quantities of genetic data coming out of hi-throughput assays. Previously,
      protoplasts have routinely been prepared from dicot tissue or cell suspension
      cultures and yet a good system for rice protoplast isolation and manipulation is
      lacking. RESULTS: We have established a rice seedling protoplast system designed
      for the rapid characterization of large numbers of genes. We report optimized
      methods for protoplast isolation from 7-14 day old etiolated rice seedlings. We
      show that the reporter genes luciferase GL2 and GUS are maximally expressed
      approximately 20 h after polyethylene glycol (PEG)-mediated transformation into
      protoplasts. In addition we found that transformation efficiency varied
      significantly with plasmid size. Five micrograms of a 4.5 kb plasmid resulted in
      60-70% transformation efficiency. In contrast, using 50 microg of a 12 kb plasmid
      we obtained a maximum of 25-30% efficiency. We also show that short interfering
      RNAs (siRNAs) can be used to silence exogenous genes quickly and efficiently. An
      siRNA targeting luciferase resulted in a significant level of silencing after
      only 3 hours and up to an 83% decrease in expression. We have also isolated
      protoplasts from cells prepared from fully green tissue. These green tissue
      derived protoplasts can be transformed to express high levels of luciferase
      activity and should be useful for assaying light sensitive cellular processes.
      CONCLUSION: We report a system for isolation, transformation and gene silencing
      of etiolated rice leaf and stem-derived protoplasts. Additionally, we have
      extended the technology to protoplasts isolated from fully green tissue. The
      protoplast system will bridge the gap between hi-throughput assays and functional
      biology as it can be used to quickly study large number of genes for which the
      function is unknown.

PMID- 16808846
TI  - Low-density lipoprotein cholesterol estimation by the Anandaraja's formula-
      confirmation.
AB  - The number of the indirect methods for LDL-C estimation is growing. Our result
      support the reliability of new Anandaraja's formula for low-density lipoprotein
      estimation from total cholesterol and triglycerides.

PMID- 16808848
TI  - Resident-generated versus instructor-generated cases in ethics and
      professionalism training.
AB  - BACKGROUND: The emphasis on ethics and professionalism in medical education
      continues to increase. Indeed, in the United States the ACGME will require
      residency programs to include professionalism training in all curricula by 2007.
      Most courses focus on cases generated by the course instructors rather than on
      cases generated by the trainees. To date, however, there has been no assessment
      of the utility of these two case discussion formats. In order to determine the
      utility of instructor-generated cases (IGCs) versus resident-generated cases
      (RGCs) in ethics and professionalism training, the author developed an innovative
      course that included both case formats. The IGCs were landmark cases and cases
      from the experience of the course instructors, while the RGCs were selected by
      the residents themselves. Residents were then surveyed to assess the strengths
      and weaknesses of each format. RESULTS: Of twenty-two second and third year
      residents, fourteen completed surveys (response rate 64%). Residents were nearly
      evenly split in preferring RGCs (38%), IGCs (31%), or not preferring one to the
      other (31%). 29% stated that they learn more from the RGCs, 21% stated that they
      learn more from the IGCs, and 50% stated that they did not find a difference in
      their learning based on format. In general, residents surveyed prefer a mix of
      formats. Residents tended to find the RGCs more relevant and interesting, and
      felt the IGCs were necessary to ensure adequate breadth of cases and concepts.
      CONCLUSION: Based on our relatively small sample at a single institution, we
      believe that educators should consider incorporating both instructor-generated
      and resident-generated cases in their ethics and professionalism curricula, and
      should evaluate the utility of such a model at their own institution. Further
      work is needed to illuminate other potential improvements in ethics and
      professionalism education.

PMID- 16808847
TI  - Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk
      of developing breast cancer among a cohort of women with benign breast disease.
AB  - BACKGROUND: A cohort study was conducted to examine the role of genetic
      polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and
      the two estrogen receptors (ESR1, ESR2) in the progression of benign breast
      disease (BBD) to breast cancer. METHODS: Among participants in an ongoing cohort
      study, 1438 Caucasian women had a breast biopsy for BBD and were successfully
      genotyped for at least one of the polymorphisms examined in this study. Genotypes
      were determined using DNA extracted from blood specimens collected in 1989.
      Incident cases of breast cancer occurring subsequent to BBD diagnosis up to 2003
      were identified through cancer registries. RESULTS: Among all participants, the
      ESR2 *5772G allele was associated with a significant decrease in the risk of
      breast cancer among women with BBD (Odds Ratio (OR) 0.38; 95% Confidence Interval
      (CI) 0.15, 0.96). Compared to the reference wild-type genotypes, marginally
      significant associations with the development of breast cancer were observed
      between carriers of the variant ESR1 - 104062T allele (OR 0.70, 95% CI 0.45,
      1.09), the variant ESR2 *38A allele (OR 1.40; 95% CI 0.88, 2.25), and the variant
      CYP1B1 453Ser allele (OR 1.48, 95% CI 0.95, 2.32). CONCLUSION: The results
      indicate that specific polymorphisms in the CYP1B1, ESR1, and ESR2 genes may play
      a role in progression of BBD to breast cancer among Caucasian women. Although
      additional studies are needed to confirm or refute our findings, these results
      suggest that genetic markers may aid in the identification of women who are at
      risk for progression of BBD to cancer.

PMID- 16808849
TI  - Human Immunodeficiency Virus type 1 in seronegative infants born to HIV-1
      infected mothers.
AB  - BACKGROUND: Some individuals repeatedly exposed to Human Immunodeficiency Virus
      do not seroconvert and are resistant to HIV infection. Here, in a pediatric
      cohort of HIV seronegative infants born of HIV-infected mothers, we have studied
      eight non-breastfed children in whom viral DNA was detected in their PBMC. Our
      objective was to assess whether silent infection in these children can be
      explained by the presence of integrated viral DNA. METHODS: The presence of viral
      DNA was corroborated by nested PCR with primers for gag and the nef/LTR regions
      of HIV-1. Integration of HIV DNA into the host genome was assessed by an Alu-LTR
      PCR. Amplicons were sequenced and phylogenetic analyzes were done. RESULTS: HIV-1
      DNA was detected in the earliest available PBMC sample from all eight infants,
      and two of them tested positive for HIV DNA at 2 years of age. Nested PCR
      resulted in the amplification of gag, nef/LTR and Alu-LTR fragments, which
      demostrated that HIV-1 DNA was integrated in the host cell genome. Each
      individual has a characteristic sequence pattern and is different from the LTR
      sequence of HXB2 prototype virus and other Mexican isolates. CONCLUSION: HIV-1
      DNA was observed in PBMC from HIV exposed seronegative children in this pediatric
      cohort.

PMID- 16808850
TI  - Whole brain radiation therapy in management of brain metastasis: results and
      prognostic factors.
AB  - PURPOSE: To evaluate the prognostic factors associated with overall survival in
      patients with brain metastasis treated with whole brain radiotherapy (WBRT) and
      estimate the potential improvement in survival for patients with brain
      metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive
      partitioning analysis (RPA) class. PATIENTS AND METHODS: From January 1996 to
      December 2000, 270 medical records of patients with diagnosis of brain
      metastasis, who received WBRT in the Hospital do Cancer Sao Paulo A.C. Camargo in
      the period, were analyzed. The surgery followed by WBRT was used in 15% of
      patients and 85% of others patients were submitted at WBRT alone; in this cohort
      134 patients (50%) received the fractionation schedule of 30 Gy in 10 fractions.
      The most common primary tumor type was breast (33%) followed by lung (29%), and
      solitary brain metastasis was present in 38.1% of patients. The prognostic
      factors evaluated for overall survival were: gender, age, Karnofsky Performance
      Status (KPS), number of lesions, localization of lesions, primary tumor site,
      surgery, chemotherapy, absence extracranial disease, RPA class and radiation
      doses and fractionation. RESULTS: The OS in 1, 2 and 3 years was 25.1%, 10.4% and
      4.3% respectively, and the median survival time was 4.6 months. The median
      survival time in months according to RPA class after WBRT was: 6.2 class I, 4.2
      class II and 3.0 class III (p < 0.0001). In univariate analysis, the significant
      prognostic factors associated with better survival were: KPS higher than 70 (p <
      0.0001), neurosurgery (p < 0.0001) and solitary brain metastasis (p = 0.009). In
      multivariate analysis, KPS higher than 70 (p < 0.001) and neurosurgery (p =
      0.001) maintained positively associated with the survival. CONCLUSION: In this
      series, the patients with higher perform status, RPA class I, and treated with
      surgery followed by whole brain radiotherapy had better survival. This data
      suggest that patients with cancer and a single metastasis to the brain may be
      treated effectively with surgical resection plus radiotherapy. The different
      radiotherapy doses and fractionation schedules did not altered survival.

PMID- 16808851
TI  - Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a
      penetrating brain injury.
AB  - The cytokines IL-1alpha and IL-1beta are induced rapidly after insults to the
      CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-1R1) has
      been regarded as essential for a normal astroglial and microglial/macrophage
      response. To determine whether abrogating signaling through the IL-1R1 will alter
      the cardinal astrocytic responses to injury, we analyzed molecules characteristic
      of activated astrocytes in response to a penetrating stab wound in wild type mice
      and mice with a targeted deletion of IL-1R1. Here we show that after a stab wound
      injury, glial fibrillary acidic protein (GFAP) induction on a per cell basis is
      delayed in the IL-1R1-null mice compared to wild type counterparts. However, the
      induction of chondroitin sulfate proteoglycans, tenascin, S-100B as well as
      glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are
      independent of IL-1RI signaling. Cumulatively, our studies on gliosis in the IL
      1R1-null mice indicate that abrogating IL-1R1 signaling delays some responses of
      astroglial activation; however, many of the important neuroprotective adaptations
      of astrocytes to brain trauma are preserved. These data recommend the continued
      development of therapeutics to abrogate IL-1R1 signaling to treat traumatic brain
      injuries. However, astroglial scar related proteins were induced irrespective of
      blocking IL-1R1 signaling and thus, other therapeutic strategies will be required
      to inhibit glial scarring.

PMID- 16808852
TI  - Does mammary ductoscopy have a role in clinical practice?
AB  - BACKGROUND: Mammary ductoscopy (MD) is a newly developed endoscopic technique
      that allows direct visualisation of the mammary ductal epithelium using sub
      millimetre fiberoptic microendoscopes inserted through the ductal opening onto
      the nipple surface. These scopes also provide working channels for insufflation,
      irrigation, ductal lavage, and possible therapeutic intervention. MD can be
      performed under local anaesthesia in the office setting. The objective of this
      study is to assess the technical feasibility of mammary ductoscopy, and examine
      its role in guiding ductal excision surgery and the early diagnosis of
      malignancy. METHODS: Mammary ductoscopy (MD) was performed using a 1 mm
      fiberoptic microendoscope (Mastascope TM) in 26 patients (age range: 14-73
      years): 13 patients undergoing mastectomy (n = 12) or lumpectomy (n = 1) for
      ductal carcinoma (including 12 cases of DCIS and one case of infiltrating ductal
      carcinoma) and 13 patients with pathological nipple discharge (PND) and benign
      breast imaging and simple discharge cytology. Of the latter group: 10 procedures
      were performed under local anaesthesia (LA) in the office setting and 3
      procedures were carried out under general anaesthesia (GA) to guide duct excision
      surgery. The ductoscopic appearances in this group were graded between 0 and 5
      (D0-D5) according to the degree of suspicion. RESULTS: Intraoperative MD was
      accomplished in 11 (84.6%) of 13 patients undergoing surgery for DCIS. MD was
      unsuccessful in 2 cases: one patient (aged 73 years) had sclerosis of the nipple
      and one patient had preoperative vital blue injection in the subareolar region as
      part of the sentinel node biopsy thus resulting in inadequate visualisation.
      Intraductal pathology was visualised in 8 (80%) of the 10 cases undergoing
      mastectomy but ductoscopic cytology was positive for malignancy in only 2 cases
      (sensitivity = 16%, specificity = 100%). In the office setting, MD was
      accomplished in 9 (90%) out of 10 patients with PND and was well tolerated (mean
      pain score = 3.8 out of 10: range 0-7). Of these 10 patients; MD was inadequate
      (D0) in one patient due to complete occlusion of lumen by the lesion, showed a
      papilloma in 3 patients (D3), duct ectasia (D2) in 3 patients, irregular
      thickening of the lumen suspicious of DCIS (D4) in one patient and non-specific
      benign findings (D2) in 2 patients. Three women with benign ductoscopy and
      ductoscopy-assisted cytology were reassured and treated conservatively. The
      remaining 7 patients had ductoscopy-guided duct excision which revealed DCIS in
      one, papilloma in 4 and benign breast disease in 2 patients. Adequate cellular
      yield was obtained in 7 (70%) out of 10 cases (benign cytology). The three
      patients who had MD under GA during microdochectomy had benign endoscopic
      appearances and final histology (one papilloma and 2 cases of duct ectasia).
      CONCLUSION: MD is technically feasible in most patients and has a potential in
      the early detection of breast cancer. The procedure can be performed safely in
      the office setting and should be considered in all patients presenting with a
      single duct PND. MD has the potential to reduce the number of duct excision
      procedures and minimise the extent of surgical resection. Ductoscopic cytology is
      not sufficiently sensitive for the diagnosis of malignancy and the development of
      a biopsy tool that obtains tissue under direct visualisation is required.

PMID- 16808853
TI  - Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early
      onset ventilator-associated pneumonia.
AB  - INTRODUCTION: To gain a better understanding of the clinical and economic
      outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA)
      infection in patients with early onset ventilator-associated pneumonia (VAP), we
      retrospectively analyzed a multihospital US database to identify patients with
      VAP over a 24 month period (2002-2003). METHOD: Data recorded included
      physiologic, laboratory, culture, and other clinical variables from 59
      institutions. VAP was defined as new positive respiratory culture after at least
      24 hours of mechanical ventilation (MV) and the presence of primary or secondary
      ICD-9-CM diagnosis codes of pneumonia. Outcomes measures included in-hospital
      morbidity and mortality for the population overall and after onset of VAP
      (duration of MV, intensive care unit [ICU] stay, in-hospital stay, and case mix
      and severity-adjusted operating cost). The overall cost was calculated at the
      hospital level using the Center for Medicare and Medicaid Services Cost/Charge
      Index for each calendar year. RESULTS: A total of 499 patients were identified as
      having VAP. S. aureus was the leading organism (31% of isolates). Patients with
      MRSA were significantly older than patients with methicillin-sensitive
      Staphylococcus aureus (MSSA; median age 74 versus 67 years, P < 0.05) and more
      likely to be medical patients. Compared with MSSA patients, MRSA patients on
      average consumed excess resources of 4.4 (95% confidence interval 0.6-8.2)
      overall MV days, 3.8 (-0.5 to +8.0) days of inpatient length of stay (LOS), 5.3
      (1.0-9.7) ICU days, and US7731 dollars (-US8393 dollars to +US23,856 dollars)
      total cost after controlling for case mix and other factors. Furthermore, MRSA
      patients needed excess resources after the onset of VAP (4.5 [95% confidence
      interval 1.0-8.1] MV days, 3.7 [-0.5 to +8.0] inpatient days, and 4.4 [0.4-8.4]
      ICU days) after controlling for the same case mix and admission severity
      covariates. CONCLUSION: S. aureus remains a common cause of VAP. VAP due to MRSA
      was associated with increased overall LOS, ICU LOS, and attributable ICU LOS
      compared with MSSA-related VAP. Although not statistically significant because of
      small sample size and large variation, the attributable excess costs of MRSA
      amounted to approximately US8000 dollars per case after controlling for case mix
      and severity.

PMID- 16808854
TI  - Evolution of candidate transcriptional regulatory motifs since the human
      chimpanzee divergence.
AB  - BACKGROUND: Despite the recent completion of the chimpanzee genome project, few
      functionally significant sequence differences between humans and chimpanzees have
      thus far been identified. Alteration in transcriptional regulatory mechanisms
      represents an important platform for evolutionary change, suggesting that a
      significant proportion of functional human-chimpanzee sequence differences may
      affect regulatory elements. RESULTS: To explore this hypothesis, we performed
      genome-wide identification of conserved candidate transcription-factor binding
      sites that have evolved since the divergence of humans and chimpanzees. Analysis
      of candidate transcription-factor binding sites conserved between mouse and
      chimpanzee yet absent in human indicated that loss of candidate transcription
      factor binding sites in the human lineage was not random but instead correlated
      with the biologic functions of associated genes. CONCLUSION: Our data support the
      notion that changes in transcriptional regulation have contributed to the recent
      evolution of humans. Moreover, genes associated with mutated candidate
      transcription-factor binding sites highlight potential pathways underlying human
      chimpanzee divergence.

PMID- 16808857
TI  - Shining new light on old principles: localization of evanescent field
      interactions at infrared-attenuated total reflection sensing interfaces.
AB  - A combined experimental and spectral ray tracing approach for identifying and
      evaluating evanescent field interactions with discrete surface deposits along a
      horizontal attenuated total reflection (HATR) element is presented. By
      experimentally depositing poly(styrene-co-butadiene) (PSCB) residues at fixed
      intervals along the measurement surface of a HATR crystal, distinct regions of
      evanescent field interaction with the surface deposits along the multi-reflection
      waveguide are visualized via infrared absorption features of PSCB. The infrared
      attenuated total reflection (IR-ATR) measurements were confirmed by spectral ray
      tracing analysis simulating transmission-absorption spectra after modeling the
      polymeric surface deposits as thin-film IR absorbing cylinders. The presented
      analytical procedures and simulations provide a generic strategy for identifying
      and evaluating "active" sensing regions along ATR elements. Additionally, the
      simulated ATR setup along with the presented spectral ray tracing procedures
      provide a virtual platform aiding the development, optimization, and integration
      of deep-sea IR-ATR sensor probes with submersible mid-infrared spectrometers for
      in situ marine monitoring applications, which was the initial motivation for
      these studies.

PMID- 16808858
TI  - Mapping bacterial surface population physiology in real-time: infrared
      spectroscopy of Proteus mirabilis swarm colonies.
AB  - We mapped the space-time distribution of stationary and swarmer cells within a
      growing Proteus mirabilis colony by infrared (IR) microspectroscopy. Colony
      mapping was performed at different positions between the inoculum and the
      periphery with a discrete microscope-mounted IR sensor, while continuous
      monitoring at a fixed location over time used an optical fiber based IR
      attenuated total reflection (ATR) sensor, or "optrode." Phenotypes within a
      single P. mirabilis population relied on identification of functional
      determinants (producing unique spectral signals) that reflect differences in
      macromolecular composition associated with cell differentiation. Inner swarm
      colony domains are spectrally homogeneous, having patterns similar to those
      produced by the inoculum. Outer domains composed of active swarmer cells exhibit
      spectra distinguishable at multiple wavelengths dominated by polysaccharides. Our
      real-time observations agree with and extend earlier reports indicating that
      motile swarmer cells are restricted to a narrow (approximately 3 mm) annulus at
      the colony edge. This study thus validates the use of an IR optrode for real-time
      and noninvasive monitoring of biofilms and other bacterial surface populations.

PMID- 16808859
TI  - Differentiation of selected Salmonella enterica serovars by Fourier transform mid
      infrared spectroscopy.
AB  - Salmonella enterica serovars include pathogens responsible for high numbers of
      foodborne salmonellosis. Fourier transform infrared (FT-IR) spectroscopy can be
      used to rapidly and accurately identify microorganisms based on unique spectra of
      bacterial cell components. The objectives of this study were to discriminate
      closely related Salmonella enterica serovars by using FT-IR spectroscopy and
      multivariate analysis and to compare the performance of three techniques for
      differentiating among Salmonella serovars. Selected serovars of S. enterica were
      streaked onto plate count agar and incubated (37 degrees C, 24 h). Isolated
      colonies were suspended in phosphate buffer or 50% ethanol (10 microL).
      Suspensions were placed on (1) ZnSe crystals for transmission, (2) disposable
      polyethylene membranes (DPM) for transmission, and (3) diamond crystal plate for
      attenuated total reflectance (ATR) analyses; all samples were dried under vacuum.
      Classification models, soft independent modeling of class analogy (SIMCA), from
      derivatized infrared spectra (1300-900 cm(-1)), discriminated among Salmonella
      serovars presumably attributed to cell's lipopolysaccharides (1000-980 cm(-1)).
      Samples on DPM required high cell density for reliable spectra. High-quality
      spectra were obtained when a single colony was suspended in ethanol or buffer and
      mounted on ZnSe crystals for transmission or diamond plate for ATR analysis.
      Prediction of unknowns, representative of serovars used to construct
      classification models, showed that all techniques were suitable for the rapid and
      accurate differentiation of Salmonella serovars.

PMID- 16808860
TI  - Transmission infrared spectroscopy as a probe of Nafion film structure: analysis
      of spectral regions fundamental to understanding hydration effects.
AB  - Transmission infrared spectroscopy was applied to investigate properties of the
      perfluorosulfonated polymer Nafion. Measurements were made on thin films formed
      by casting the polymer from solution onto ZnSe windows. Effects of water vapor
      permeation were studied. A complex band structure between 1350 and 1100 cm(-1)
      was analyzed qualitatively by fitting the region to Gaussian functions. Features
      associated with vibrational modes of -CF(2) and -SO(3)(-) groups were identified
      and observed to be sensitive to film hydration. The intensities of bands for the 
      SO(3)(-) modes increased with film hydration, while bands assignable to -CF(2)
      modes decreased. The results were applied to interpret infrared difference
      spectra of Nafion and shed light on the complicated features that appear.
      Vibrational bands for water were also examined. In partially hydrated films, the
      stretching mode of the free -OH group for interfacial water present in pores and
      channels of the polymer and bands for hydrated proton clusters were detected.

PMID- 16808861
TI  - Quadrature orthogonal signal corrected two-dimensional correlation spectroscopy.
AB  - Orthogonal signal correction (OSC) removes a substantial part of the spectral
      response that is orthogonal to the selected external variable. The combined use
      of OSC filtering and two-dimensional (2D) correlation analysis was proposed in
      the previous study (Wu, Noda, Meersman, and Ozaki, J. Mol. Struct., 2006, paper
      in press) to enable one to obtain high-quality 2D correlation spectra by
      eliminating any information unrelated to the external variables. However, the
      direct application of OSC to two-dimensional (2D) correlation analysis will
      result in the loss of the component that is significantly perpendicular to the
      external variable but also is the portion significant to the asynchronous 2D
      correlation analysis. Therefore, in order to avoid the problem of losing the
      valuable asynchronous 2D correlation information, the present study proposes a
      modified OSC filtering method, which is called quadrature OSC (QOSC) filtering.
      By replacing the external variable vector y used for OSC filtering with a two
      column Y matrix consisting of y and its Hilbert-Noda transformation, the
      component of the spectral data asynchronously correlated to the external variable
      y is preserved. The performance of this technique on two simulated spectra data
      sets with a strong contaminant band and systematic noises has demonstrated that
      QOSC filtering 2D correlation analysis enables not only the elimination of the
      influence of signals that are unrelated to the external variable but also the
      preservation of the portions of information in the data matrix that are 90
      degrees out of phase with y. It enables OSC 2D to deal with the problems of
      losing the portion of information that is perpendicular to the external variable
      y but is quite significant to the 2D correlation analysis.

PMID- 16808862
TI  - Temperature-dependent structural changes in hydrogen bonds in microcrystalline
      cellulose studied by infrared and near-infrared spectroscopy with perturbation
      correlation moving-window two-dimensional correlation analysis.
AB  - Temperature-dependent structural changes in hydrogen bonds (H-bonds) in
      microcrystalline cellulose (MCC) were investigated by infrared (IR) and near
      infrared (NIR) spectroscopy. The O-H stretching fundamentals and their first
      overtone bands were employed to explore the structural changes. In order to
      analyze the overlapping OH bands due to various H-bonds, perturbation-correlation
      moving-window two-dimensional (PCMW2D) correlation spectroscopy was applied to
      the IR and NIR data. Typical spectral variation temperatures were visualized by
      the PCMW2D correlation analysis. Structural changes in the strong H-bonds in MCC
      gradually occur in the temperature region of 25-130 degrees C, and they become
      greater above 130 degrees C. Both OH groups with H-bonds of intermediate strength
      and very weak H-bonds arise from the structural change of strong H-bonds in the
      temperature region of 40-90 degrees C, whereas the appearance of the latter OH
      groups with very weak H-bonds gradually becomes dominant above 90 degrees C. It
      is revealed from the present study that the glass transition at 184 degrees C
      induces the changes in the H-bonds in the Ibeta and the O3-H3...O5 intrachain H
      bonds. Band assignments for the O-H stretching first overtone vibration region
      are proposed based on the results of the PCMW2D correlation analyses.

PMID- 16808863
TI  - Fast and robust method for the determination of microstructure and composition in
      butadiene, styrene-butadiene, and isoprene rubber by near-infrared spectroscopy.
AB  - In the tire industry, synthetic styrene-butadiene rubber (SBR), butadiene rubber
      (BR), and isoprene rubber (IR) elastomers are essential for conferring to the
      product its properties of grip and rolling resistance. Their physical properties
      depend on their chemical composition, i. e., their microstructure and styrene
      content, which must be accurately controlled. This paper describes a fast,
      robust, and highly reproducible near-infrared analytical method for the
      quantitative determination of the microstructure and styrene content. The
      quantitative models are calculated with the help of pure spectral profiles
      estimated from a partial least squares (PLS) regression, using (13)C nuclear
      magnetic resonance (NMR) as the reference method. This versatile approach allows
      the models to be applied over a large range of compositions, from a single BR to
      an SBR-IR blend. The resulting quantitative predictions are independent of the
      sample path length. As a consequence, the sample preparation is solvent free and
      simplified with a very fast (five minutes) hot filming step of a bulk polymer
      piece. No precise thickness control is required. Thus, the operator effect
      becomes negligible and the method is easily transferable. The root mean square
      error of prediction, depending on the rubber composition, is between 0.7% and
      1.3%. The reproducibility standard error is less than 0.2% in every case.

PMID- 16808864
TI  - Multi-objective genetic algorithm-based sample selection for partial least
      squares model building with applications to near-infrared spectroscopic data.
AB  - In this study, multi-objective genetic algorithms (GAs) are introduced to partial
      least squares (PLS) model building. This method aims to improve the performance
      and robustness of the PLS model by removing samples with systematic errors,
      including outliers, from the original data. Multi-objective GA optimizes the
      combination of these samples to be removed. Training and validation sets were
      used to reduce the undesirable effects of over-fitting on the training set by
      multi-objective GA. The reduction of the over-fitting leads to accurate and
      robust PLS models. To clearly visualize the factors of the systematic errors, an
      index defined with the original PLS model and a specific Pareto-optimal solution
      is also introduced. This method is applied to three kinds of near-infrared (NIR)
      spectra to build PLS models. The results demonstrate that multi-objective GA
      significantly improves the performance of the PLS models. They also show that the
      sample selection by multi-objective GA enhances the ability of the PLS models to
      detect samples with systematic errors.

PMID- 16808865
TI  - Application of multivariate curve resolution to chemical process control of an
      esterification reaction monitored by near-infrared spectroscopy.
AB  - Multivariate curve resolution-alternating least squares (MCR-ALS) methodology was
      applied to near-infrared spectroscopy (NIR) data for the esterification reaction
      between glycerol and a mixture of caprylic and capric acids. Batch reaction
      processes were conducted either at the laboratory scale or at an industrial
      plant, while NIR data were obtained from samples withdrawn during the reaction
      processes. The process has been monitored via two typical parameters for this
      type of reaction, namely, the acid value (AV) and the hydroxyl value (OHV).
      Spectral and concentration profiles were estimated by applying soft-modeling MCR
      ALS to a column-wise augmented data matrix with pure spectra of the components,
      and concentration values for the acid were used as a soft-equality constraint.
      The estimated concentration profiles have been compared with the AV and OHV
      values, and the estimated spectral profiles were used to predict the
      concentration profiles for new batches. Good results have been obtained in terms
      of RMSE for the prediction of AV and OHV.

PMID- 16808866
TI  - Influence of near-infrared radiation on the pKa values of L-phenylalanine.
AB  - The effect of pH on L-phenylalanine (L-phe) before and after exposure to near
      infrared (NIR) radiation (15 min, 700-2000 nm) was investigated by attenuated
      total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy.
      Characteristic bands of L-phe were described and the pK(a) values were retrieved
      from IR spectra by using an intensity ratio method according to our recent paper
      (Olsztynska et al., Appl. Spectrosc. 55, 901 (2001)). It has been found that the
      irradiation process modifies pK(a) values of L-phe. The spectroscopic study
      clearly shows the shift of acid-base equilibrium after exposure to NIR radiation.
      The phenomenon is due to modification of the water structure. Intra- and
      intermolecular hydrogen bonds weaken, which could induce conformational changes
      of the phe molecule. Subsequently, hydrophobic interactions strongly increase.
      These processes favor aggregation of phe molecules, which leads to deprotonation
      of the -NH(3)(+) to -NH(2) group and protonation of the -COO(-) to -COOH group,
      changing the pK(a) values.

PMID- 16808867
TI  - Uncertainty analysis of visible and near-infrared data of hydrocarbons.
AB  - Measurement of physical and chemical properties of hydrocarbons plays an
      important role in the exploration and production of oil wells. In situ
      measurement of chemical properties of hydrocarbons makes use of visible and near
      infrared (vis-NIR) absorption spectra of hydrocarbons. Uncertainty analysis of
      these fluid properties is central to developing a fundamental understanding of
      the distribution of hydrocarbons in the reservoir. In this manuscript, we
      describe an algorithm called the fluid comparison algorithm (FCA), which provides
      a statistical framework to quantify and compare hydrocarbon fluid properties and
      associated uncertainties derived from vis-NIR measurements. The inputs to FCA are
      the magnitude and uncertainty of vis-NIR spectroscopy data of two hydrocarbons.
      The output of FCA is a probability that two fluids are statistically different.
      FCA lays the foundations for subsequent optimization and capture of
      representative reservoir hydrocarbons. Furthermore, in some circumstances, it can
      also enable real-time decisions to identify reservoir compartmentalization and
      hydrocarbon composition gradients in natural oil reservoirs.

PMID- 16808868
TI  - Coded aperture Raman spectroscopy for quantitative measurements of ethanol in a
      tissue phantom.
AB  - Coded aperture spectroscopy allows for sources of large etendue to be efficiently
      coupled into dispersive spectrometers by replacing the traditional input slit
      with a patterned mask. We describe a coded aperture spectrometer optimized for
      Raman spectroscopy of diffuse sources, (e.g., tissue). We provide design details
      of the Raman system, along with quantitative estimation results for ethanol at
      non-toxic levels in a lipid tissue phantom. With 60 mW of excitation power at 808
      nm, leave-one-out and blind cross-validation of partial least squares (PLS)
      regression models achieve r(2) > 0.98. Leave-one-out cross-validation
      demonstrates prediction errors of <15% at the common legal limit for intoxication
      (17.4 mmol/L = 0.08% by vol) and the best blind cross-validation achieves <12%
      error at this concentration.

PMID- 16808869
TI  - On-line content uniformity determination of tablets using low-resolution Raman
      spectroscopy.
AB  - Analytical techniques for rapid and nondestructive content uniformity
      determination of pharmaceutical solid dosage forms have been studied for several
      years in an effort to replace the traditional wet chemistry procedures, which are
      labor intensive and time consuming. Both Raman spectroscopy and near-infrared
      spectroscopy have been used for this purpose, and predictability errors are
      approaching those of the traditional techniques. In this study, a low-resolution
      Raman spectrometer was utilized to demonstrate the feasibility of both rapid at
      line and on-line determination of tablet content uniformity. Additionally,
      sampling statistics were reviewed in an effort to determine how many tablets
      should be assayed for specific batch sizes. A good correlation was observed
      between assay values determined by high-performance liquid chromatography and
      Raman analysis. Due to rapid acquisition times for the Raman data, it was
      possible to analyze far more samples than with wet chemistry methods, leading to
      a better statistical description of variation within the batch. For at-line
      experiments, the sampling volume was increased by rotating the laser beam during
      the acquisition period. For the on-line experiments, the sampling volume was
      increased by sampling from a stream of tablets moving underneath the Raman probe
      on a conveyor system. Finally, an approach is proposed for monitoring content
      uniformity immediately following the compaction process. In conclusion, Raman
      spectroscopy has potential as a rapid, nondestructive technique for at- or on
      line determination of tablet content uniformity.

PMID- 16808871
TI  - High-order statistical blind deconvolution of spectroscopic data with a Gauss
      Newton algorithm.
AB  - The spectroscopic data recorded by a dispersion spectrophotometer are usually
      degraded by the response function of the instrument. To improve the resolving
      power, double or triple cascade spectrophotometers and narrow slits have been
      employed, but the total flux of the radiation available decreases accordingly,
      resulting in a lower signal-to-noise ratio (SNR) and a longer measurement time.
      However, the spectral resolution can be improved by mathematically removing the
      effect of the instrument response function. A high-order statistical Gauss-Newton
      algorithm is proposed to blindly deconvolve the measured spectroscopic data. The
      true spectrum and the instrument response function are estimated simultaneously.
      Experiments on artificial and real measured spectroscopic data demonstrate the
      feasibility of this method.

PMID- 16808870
TI  - Determination of mechanical strength properties of hemp fibers using near
      infrared fourier transform Raman microspectroscopy.
AB  - Fourier transform near-infrared (FT-NIR) Raman microspectroscopy was adopted for
      analyzing the micro mechanical tensile deformation behavior of cellulosic plant
      fibers. Mechanical strength parameters such as tensile strength, failure strain,
      and Young's modulus of diversified hemp fibers were determined within the range
      of single fiber cells and fiber filaments. The analysis of fiber deformation at
      the molecular level was followed by the response of a characteristic Raman signal
      of fiber cellulose that is sensitive to the tensile load applied. The frequency
      shift of the Raman signal at 1095 cm(-1) to lower wavenumbers was observed when
      the fibers were subjected to tensile strain. Microstructural investigations using
      electron microscopy under environmental conditions supported the discussion of
      mechanical properties of hemp fibers in relation to several fiber variabilities.
      Generally, mechanical strength properties of diversified hemp fibers were
      discussed at the molecular, microstructural, and macroscale level. It was
      observed that mechanical strength properties of the fibers can be controlled in a
      broad range by appropriate mercerization parameters such as alkali concentration,
      fiber shrinkage, and tensile stress applied to the fibers during the alkaline
      treatments.

PMID- 16808872
TI  - Origins of PM10 determined by the micro-proton induced X-ray emission spectra of
      single aerosol particles.
AB  - The micro-proton induced X-ray emission (micro-PIXE) spectrum of a single aerosol
      particle (SAP) was considered as its fingerprint for tracing its origin. A proton
      microprobe was used to extract fingerprints of SAPs. Environmental monitoring
      samples of PM(10) were collected from a heavy industrial area of Shanghai and
      were analyzed by proton microprobe for finding their pollution sources. In order
      to find the sources of SAPs collected from environmental monitoring sites, a
      fingerprint database of SAPs collected from various pollution sources was
      established. The origins of samples collected through environmental monitoring
      were identified by comparison of the micro-PIXE spectra of SAPs with those of
      SAPs in the fingerprint database using a pattern recognition technique. The
      results of this study show that most of the measured PM(10) is derived from
      metallurgic industry, soil dust, coal combustion, automobile exhaust, and
      motorcycle exhaust. The study also shows that the proton microprobe is an ideal
      tool for the analysis of SAPs. The unidentified particles of PM(10) are
      classified into seven classes by hierarchical cluster analysis based on the
      element peak intensity in the spectra.

PMID- 16808874
TI  - Editorial: Advances in biology and treatment of malignant brain gliomas. Stem
      cells and neurosciences.

PMID- 16808875
TI  - Human neural stem cell differentiation following transplantation into spinal cord
      injured mice: association with recovery of locomotor function.
AB  - Stem cells are under intense investigation as potential therapeutics for central
      nervous system (CNS) injury and disease. However, several reports have suggested
      that stem cells grown as neurospheres and transplanted into an injured
      environment preferentially differentiate into astrocytes, contributing to glial
      scar. Further, the relationship between functional recovery and cell
      transplantation has not been empirically investigated in early studies. Using
      severe combined immunodeficient (scid) mice to minimize xenograft rejection, we
      report that prospectively isolated human fetal CNS-derived stem cells grown as
      neurospheres (hCNS-SCns) survive, migrate and express differentiation markers for
      neurons and oligodendrocytes after long-term engraftment in spinal cord injured
      (SCI) NOD-scid mice. Only rarely do these cells differentiate into glial
      fibrillary acidic protein (GFAP)-positive astrocytes, with no apparent
      contribution to glial scar. hCNS-SCns engraftment was associated with recovery of
      locomotor function. After long-term engraftment and stable behavioral plateaus in
      recovery were achieved (4 months post-transplantation), locomotor improvements
      were abolished by selective ablation of human cells with diphtheria toxin (DT).
      These data suggest that hCNS-SCns survival is required for locomotor recovery,
      possibly via differentiation and integration of human cells in the mouse host or
      continuous supply of trophic or other support necessary for gains in host cell
      function.

PMID- 16808876
TI  - Intraoperative visualization for resection of gliomas: the role of functional
      neuronavigation and intraoperative 1.5 T MRI.
AB  - OBJECTIVE: To investigate how functional neuronavigation and intraoperative high
      field magnetic resonance imaging (MRI) influence glioma resection. METHODS: One
      hundred and thirty-seven patients [World Health Organization (WHO) grade I: 20;
      II: 19; III: 41; IV: 57] underwent resection for supratentorial gliomas in an
      operative suite equipped with intraoperative high-field MRI and microscope-based
      neuronavigation. Besides standard anatomical image data including T1- and T2
      weighted sequences, various functional data from magnetoencephalography (n=37),
      functional MRI (n=65), positron emission tomography (n=8), MR spectroscopy (n=28)
      and diffusion tensor imaging (n=55) were integrated in the navigational setup.
      RESULTS: Intraoperative MRI showed primary complete resection in 27% of all
      patients (I: 50%; II: 53%; III: 2%; IV: 28%). In 41% of all patients (I: 40%; II:
      26%; III: 66%; IV: 28%) the resection was extended owing to intraoperative MRI
      increasing the percentage of complete resections to 40% (I: 70%; II: 58%; III:
      17%; IV: 40%). Integrated application of functional navigation resulted in low
      post-operative morbidity with a transient new neurological deficit in 10.2%
      (paresis: 8.8% and speech disturbance: 1.4%) decreasing to a permanent deficit in
      2.9% (four of 137 patients with a new or increased paresis). CONCLUSIONS: The
      combination of intraoperative MRI and functional navigation allows safe extended
      resections in glioma surgery. However, despite extended resections, still in the
      majority of the grade III and IV gliomas no gross total resection could be
      achieved owing to the extension of the tumor into eloquent brain areas.
      Intraoperative MRI data can be used to localize the tumor remnants reliably and
      compensate for the effects of brain shift.

PMID- 16808877
TI  - Influence of local environment on the differentiation of neural stem cells
      engrafted onto the injured spinal cord.
AB  - OBJECTIVES: In vitro, neural stem cells (NSCs) proliferate as undifferentiated
      spheroids and differentiate into neurons, astrocytes and oligodendrocytes. These
      features make NSCs suitable for spinal cord (SC) reconstruction. However, in vivo
      experiments have demonstrated that in the injured SC transplanted NSCs either
      remain undifferentiated or differentiate into the astrocytic phenotype. The
      microenvironment of the injured SC is believed to play a crucial role in driving
      the differentiation of the engrafted NSCs. Here, we tested the hypothesis that
      inflammatory cytokines (ICs) may be involved in the restricted differentiation of
      NSCs after grafting onto the injured SC. METHODS: As the first step, we used
      immunohistochemistry to analyse the expression of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta and interferon (IFN)-gamma in the normal SC of mice
      and following traumatic injury. Then, we investigated whether a combination of
      TNF-alpha, IL-1beta and IFN-gamma may affect the phenotype of murine NSCs in
      vitro. RESULTS: We found that TNF-alpha, IL-1beta and IFN-gamma, which are absent
      in the normal SC, are all expressed in the injured SC and the expression of these
      cytokines follows a timely tuned fashion with IFN-gamma being detectable as long
      as 4 weeks after injury. In culture, exposure of proliferating NSCs to a
      combination of TNF-alpha, IL-1beta and IFN-gamma was per se sufficient to induce
      the astrocytic differentiation of these cells even in the absence of serum.
      CONCLUSIONS: In the traumatically injured SC, differentiation of engrafted NSCs
      is restricted towards the astrocytic lineage because of the inflammatory
      environment. ICs are likely to play a major role in differentiation of NSCs in
      the in vivo conditions.

PMID- 16808878
TI  - Cyclin E1 knockdown induces apoptosis in cancer cells.
AB  - OBJECTIVES: Cyclin E1 is expressed during the late G1 phase of the cell cycle and
      mediates the initiation of DNA synthesis by activating cyclin-dependent kinases 2
      (CDK2). Abnormally high levels of cyclin E1 expression have frequently been found
      in cancer cells. Here, we investigate the effect of cyclin E1 knockdown on cancer
      cells. METHODS: RNA interference, expressed from a DNA-based retroviral vector,
      was used to knockdown cyclin E1 in adenocarcinoma (HeLa), breast (MDA-MB-31) and
      glioblastoma (U-373-MG) cell lines and an explant from one glioma patient (GB-LP
      2). RESULTS: We have obtained very efficient depletion of cyclin E1 protein (over
      80%) and considerable apoptotic induction (50-70%) after 96 hours post-infection.
      The ability of U-373-MG cells to induce tumor growth in nude mice was also
      abolished after cyclin E1 knockdown. DISCUSSION: Our results indicate that
      retrovirus carrying the DNA to be transcribed into a short hairpin RNA (shRNA)
      against cyclin E1 could be used as a therapeutic agent for cancer therapy.

PMID- 16808879
TI  - New strategies for repairing the injured spinal cord: the role of stem cells.
AB  - Thanks to advances in the stem cell biology of the central nervous system, the
      previously unconceivable regeneration of the damaged spinal cord is approaching
      reality. A number of potential strategies aim to optimize functional recovery
      after spinal cord injury. They include minimizing the progression of secondary
      injury, manipulating the inhibitory environment of the spinal cord, replacing
      lost tissue with transplanted cells or peripheral nerve grafts, remyelinating
      denuded axons and maximizing the intrinsic regenerative potential of endogenous
      progenitor cells. We review the application of stem cell transplantation to the
      spinal cord, emphasizing the use of embryonic stem cells for remyelinating
      damaged axons. Recent advancements in neural injury and repair, and the progress
      towards development of neuroprotective and regenerative interventions are
      discussed.

PMID- 16808880
TI  - In vitro analysis of mouse neural stem cells genetically modified to stably
      express human NGF by a novel multigenic viral expression system.
AB  - OBJECTIVES: The purpose of this study was to characterize mouse neural stem cells
      (NSC) transduced by a multigenic lentiviral vector (LV) and stably express
      recombinant human nerve growth factor (rhNGF). We obtained NSC-derived cell lines
      which express human NGF in relevant amount to exploit their ability for
      therapeutic applications. METHODS: We constructed advanced multigenic LV vectors
      which contain a tricistronic cassette to express simultaneously up to three
      independent genes: (1) rhNGF (beta subunit); (2) EGFP (enhanced green fluorescent
      protein) and (3) Neo(R) (neomycin antibiotic resistance gene). Lentiviruses were
      obtained by transfecting LV constructs plus helper plasmids in human embryonic
      kidney (HEK)-293T packaging cells. Lentiviral virions were released in culture
      media and subsequent used to infect mouse NSC. Genetycin 418-resistant NSC were
      obtained after 1 month of selection in the presence of antibiotic (G418). Levels
      of human NGF secreted by rhNGF-NSC were determined by ELISA (enzyme-linked
      immunosorbent assay). Features of multipotentiality of engineered NSC-derived
      cell lines versus naive cells (control-NSC) were assessed by immunocytochemical
      analysis in differentiation conditions. Self-renewal of NSC was tested by
      neurospheres assay (NSA). RESULTS: Levels of secreted human NGF, from conditioned
      media obtained by rhNGF-NSC cultures, were found to be elevated in either
      proliferation or differentiation conditions as compared with control cells.
      Moreover, released hNGF demonstrated biologic activity on PC12 cells by a
      functional test of neurite outgrowth. Immunocytochemical analysis revealed that
      engineered NSC showed to be all positives for EGFP. After thirty passages in
      vitro in the presence of G418, engineered cells versus naive NSC cultures
      maintained their multipotentiality to differentiate into neurons, astrocytes and
      oligodendrocytes. Furthermore, it was found that rhNGF-NSC-derived neurons
      expressed choline acetyltransferase (ChAT) and displayed an enhanced axonal
      growth. NSA showed an altered sphere forming frequency either in rhNGF-NSC or
      both group of control NSC. DISCUSSION: Lentivirus-mediated rhNGF gene transfer
      into NSC was achieved using a new version of LV vectors. We obtained rhNGF-NSC
      derived cell lines which released hNGF to high levels in the culture medium. The
      expression of neural differentiation markers, like microtubule associated protein
      2 (MAP2) (a/b), glial fibrillary acidic protein (GFAP) and chondroitin sulphate
      proteoglycan (NG2), was not enhanced in rhNGF-NSC compared with control cells.
      Secreted hNGF increased axonal sprouting by rhNGF-NSC-derived neurons which was
      associated with ChAT expression. rhNGF-NSC may prospectively be good candidates
      for the treatment of either neurodegenerative diseases such as Alzheimer disease
      or central nervous system injuries.

PMID- 16808882
TI  - Radioimmunotherapy of brain tumor.
AB  - Despite years of intensive research, the prognosis of high-grade gliomas (HGG)
      remains poor, as these tumors are highly resistant to currently available
      therapies. Therefore, there is a need for the development of new therapeutic
      strategies, such as the use of monoclonal antibodies (MoAbs) in association with
      radioisotopes, in order to achieve better responses and prognosis. This article
      describes our experience in radioimmunotherapy (RIT) with MoAbs and tumor pre
      targeting with the avidin-biotin system, either in systemic or locoregional
      administrations. This therapy offers the exciting prospect of increasing the
      specificity of tumor cell irradiation with radioisotopes. We suggest that RIT,
      both systemic and locoregional, should be used as part of a combined modality
      approach: in combination with surgery, radiotherapy and chemotherapy.

PMID- 16808881
TI  - Endogenous stem and precursor cells for demyelinating diseases: an alternative
      for transplantation?
AB  - Remyelination can be very effective in human. However, this process ultimately
      fails in multiple sclerosis (MS). In this paper, we discuss the possibility of
      stimulating endogenous oligodendrocyte precursors to participate in remyelination
      in experimental models (rat and primate Callithrix jacchus) of MS through thyroid
      hormone (TH) administration. TH is in fact known to be a key signal in brain
      development, oligodendrocyte development and myelin protein gene expression
      regulation.

PMID- 16808883
TI  - Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral
      sclerosis.
AB  - OBJECTIVES: Our study was aimed to evaluate the feasibility and safety of
      intraspinal cord implantation of autologous mesenchymal stem cells (MSCs) in a
      few well-monitored amyotrophic lateral sclerosis (ALS) patients. METHODS: Seven
      patients affected by definite ALS were enrolled in the study and two patients
      were treated for compassionate use and monitored for at least 3 years. Bone
      marrow was collected from the posterior iliac crest according to the standard
      procedure and MSCs were expanded ex vivo according to Pittenger's protocol. The
      cells were suspended in 2 ml autologous cerebrospinal fluid and transplanted into
      the spinal cord by a micrometric pump injector. RESULTS: The in vitro expanded
      MSCs did not show any bacterial o fungal contamination, hemopoietic cell
      contamination, chromosomic alterations and early cellular senescence. No patient
      manifested major adverse events such as respiratory failure or death. Minor
      adverse events were intercostal pain irradiation and leg sensory dysesthesia,
      both reversible after a mean period of 6 weeks. No modification of the spinal
      cord volume or other signs of abnormal cell proliferation were observed. A
      significant slowing down of the linear decline of the forced vital capacity was
      evident in four patients 36 months after MSCs transplantation. CONCLUSIONS: Our
      results demonstrate that direct injection of autologous expanded MSCs into the
      spinal cord of ALS patients is safe, with no significant acute or late toxicity,
      and well tolerated. The clinical results seem to be encouraging.

PMID- 16808884
TI  - Dendritic cells pulsed with glioma lysates induce immunity against syngeneic
      intracranial gliomas and increase survival of tumor-bearing mice.
AB  - In recent years, the use of dendritic cells (DC), the most powerful antigen
      presenting cells, has been proposed for the creation of vaccines against gliomas.
      This approach has been demonstrated to be safe and non-toxic in phase I or I-II
      trials (2, 3). Immunotherapy plays a central role in the search for new
      treatments for glioblastoma multiforme (GBM). In particular, several phase I
      studies have been performed using DC pulsed by GBM proteins as a vaccine for
      patients with relapsing GBM. The studies demonstrated that DC vaccination is safe
      and may produce a significant increase in overall survival. As the first step in
      the preparation of appropriate conditions for a clinical evaluation in Italy, we
      have performed pre-clinical experiments on immune-competent mice injected intra
      cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra
      tumorally with DC loaded with a GL261 homogenate. These results show that
      vaccination with DC pulsed with a tumor lysate increases considerably survival in
      mice bearing intracranial glioblastomas and supports the development of DC-based
      clinical trials for patients with glioblastomas that do not respond to standard
      therapies.

PMID- 16808885
TI  - Telomerase inhibition impairs tumor growth in glioblastoma xenografts.
AB  - Telomerase is a specialized DNA polymerase that is required to replicate the ends
      of linear chromosomes, the telomeres. The majority of human cancers express high
      levels of telomerase activity that is permissive for tumor growth because it
      provides cells with an extended proliferative potential. Additionally, telomerase
      exerts cell growth promoting functions and favors cell survival. Human
      glioblastoma multiforme (GBM) cells express high level of telomerase activity
      owing to the overexpression of human telomerase reverse transcriptase (hTERT),
      the limiting subunit of the enzyme. Here we used retroviral mediated RNA
      interference to dampen down telomerase activity in two distinct human GBM cell
      lines, U87MG and TB10. Substantial decrease of hTERT mRNA and telomerase activity
      had only minimal effects on telomere length maintenance, cell growth and survival
      in vitro. On the contrary, development of tumors upon subcutaneously grafting of
      U87MG and TB10 cells and intracranial implantation of U87MG cells in nude athymic
      mice was strongly reduced by telomerase inhibition.

PMID- 16808886
TI  - Molecular markers of gliomas: a clinical approach.
AB  - Over the last decade, the knowledge on the molecular genetic background of
      gliomas has dramatically increased. This information provides the basis for the
      molecular target therapies and molecular tests serve to complement the subjective
      nature of histopathologic criteria and add useful data regarding response to
      treatments and prognosis. In particular, the use of loss of heterozygosity (LOH)
      and methylation specific polymerase chain reaction (PCR) (MSP) based testing of
      gliomas is already in place and used clinically in several centers. This paper
      provides a brief overview of these molecular genetic aberrations and discusses
      the clinical utility, as well as the advantages and disadvantages of such
      approach. Newly developed molecular techniques, such as LOH testing, fluorescence
      in situ hybridization (FISH), DNA sequencing and MSP, are currently being
      employed in assessment of gliomas in some laboratories. However, the clinical use
      of some markers and the context in which the information obtained should be used
      are still not entirely understood. Therefore, this paper will focus on validation
      and implementation of molecular testing in gliomas, with emphasis on LOH on
      chromosomes 1p, 19q, 17p and 10q and O(6)-methylguanine-DNA methyltransferase
      (MGMT) methylation status.

PMID- 16808887
TI  - Convection-enhanced delivery in the treatment of malignant glioma.
AB  - Despite advancements in glioma therapy, median survival remains low because of
      rapid post-resection recurrence. A regional method of drug delivery to address
      local invasion may improve clinical outcomes. Convection-enhanced delivery (CED)
      is a novel therapy that allows distribution of substances throughout the
      interstitium via positive-pressure infusion. Studies using various agents have
      investigated the parameters that affect CED including infusion rate, cannula
      size, infusion volume, extracellular space, particle characteristics and tumor
      tissue structure. We review models of small animal glioma that have been
      successfully treated using different substances administered through CED,
      particularly our favorable results using topotecan in a C6 rat glioma model. We
      also review Phase I/II trials utilizing CED which have shown promising response
      rates and acceptable safety profiles. Future studies should include prospective
      clinical trials and investigation of novel antitumor agents that are ineffective
      with systemic delivery. Development of a large animal glioma model would enhance
      pre-clinical investigation of CED. Clinically, methods to monitor distribution of
      therapeutic agents and real-time patient response should likewise be explored.

PMID- 16808888
TI  - Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated
      with the risk of cerebral infarction in Chinese Han population.
AB  - OBJECTIVES: It has been reported that human serum paraoxonase (PON1) gene is
      associated with coronary heart disease (CHD) and diabetes mellitus (DM). However,
      little is known about the role of PON1 gene polymorphism in cerebral infarction
      (CI). For this, we have investigated the relationship between PON1 gene
      polymorphisms, Q192R and L55M, and CI in Chinese Han population. METHODS: The
      PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals,
      were determined by polymerase chain reaction (PCR) and restriction enzyme
      digestion. Their allele frequencies were then determined. The association of the
      PON1 gene polymorphism with the risk of CI was analysed by statistical analysis
      software. RESULTS: The frequencies of PON1-Q192R genotypes in CI and control
      group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR)
      respectively. There is no significant difference in PON1-Q192R genotype (p=0.566)
      and allele frequencies (p=0.505) between CI patients and controls. The
      frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5%
      (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and
      control group. No significant difference in genotype (p=0.289) and allele
      (p=0.296) distribution between CI patients and controls was observed. DISCUSSION:
      Our results suggest that the human serum paraoxonase polymorphisms, Q192R and
      L55M, are not associated with the risk of cerebral infarction in Chinese Han
      population.

PMID- 16808889
TI  - Balance performance in three forms of multiple sclerosis.
AB  - OBJECTIVES: To compare and document balance performance between patients with
      multiple sclerosis (MS) and healthy control subjects and balance performance
      among patients with different MS forms using a set of clinical balance tests.
      MATERIAL AND METHODS: Twenty eight primary progressive (PPMS), 34 secondary
      progressive (SPMS), and 62 relapsing remitting (RRMS), totalling 124 MS patients
      were included in the present study. Results from patients were compared with
      those of 31 healthy control subjects matching in age, gender, weight and height.
      Ashworth scale, mini-mental state examination and motricity index were used
      consecutively to evaluate spasticity, cognitive impairment and lower extremity
      muscle strength. Vision, sensation, proprioception, cerebellar and vestibular
      tests were also performed on the patients. The balance performance was evaluated
      using a set of clinical tests including steady stance tests (eyes in opened and
      closed positions, feet apart, feet together, stride stance, tandem stance and
      single stance), self-generated perturbations (functional reach, arm raise and
      step test), external perturbations, Tinetti-gait and 10 m gait time tests.
      RESULTS: There were no differences in age, sex, weight, height, sense impairment
      and lower extremity strength in patients with the three MS forms (p>0.05). No
      difference was found among patients with the three MS forms and the control
      subjects in the test of eyes closed with feet apart (p>0.05). The PPMS patients
      in all the balance tests except tests of eyes closed with feet apart and eyes
      opened with feet together, SPMS patients in all the balance tests except that of
      eyes closed with feet apart and RRMS patients in tandem stance, single leg
      stance, self-generated perturbations, external perturbations, Tinetti-gait and 10
      m gait time tests had weaker balance than the control subjects (p<0.001). There
      were some differences between patients in the PPMS and SPMS groups in the eyes
      closed and feet apart test, between patients in the PPMS and RRMS groups in all
      the balance tests except eyes closed and feet apart and eyes opened and feet
      together tests and between patients in SPMS and RRMS group in all the balance
      tests except right and left arm raised tests (p<0.001). CONCLUSION: Balance in MS
      patients is impaired. The results of the present study show that there is more
      impairment in progressive MS forms than in RRMS. Meanwhile, patients with
      progressive MS are more likely to fall.

PMID- 16808890
TI  - MRI lesions after invasive therapy of carotid artery stenosis: a risk-modeling
      analysis.
AB  - BACKGROUND: Diffusion-weighted imaging (DWI) abnormalities can frequently be
      detected after carotid endarterectomy (CEA) and carotid angioplasty with stent
      placement (CAS) of the carotid arteries. We looked for possible predictors for
      the development of DWI lesions during the intervention. METHODS: We investigated
      41 patients who underwent CAS without protection devices and 93 patients who
      underwent CEA. DWI studies were performed 1 day before and after the
      intervention. RESULTS: Ischemic complications consisted of two strokes (2.2%) in
      the CEA group and one stroke (2.4%) in the CAS group. DWI lesions were detected
      in 28.0% of all patients after intervention. Using a multivariate regression
      analysis, diabetes mellitus (DM), hyperlipidemia, symptomatic stenosis, age and
      CAS were found to be significant predictors for the occurrence of DWI lesions.
      CONCLUSIONS: DWI is an objective and highly sensitive method for monitoring
      interventions of the carotid arteries. Our results point to an increased risk of
      patients with diabetes and hyperlipidemia to develop DWI lesions during invasive
      therapy of the ICA.

PMID- 16808891
TI  - Early changes in the cervical foraminal area after anterior interbody fusion with
      polyetheretherketone (PEEK) cage containing synthetic bone particulate: a
      prospective study of 20 cases.
AB  - OBJECTIVES: Although the use of intervertebral fusion after anterior cervical
      microdiscectomy remains controversial, a new surgical device is proposed for use
      in intervertebral fusion instead of bone graft. The authors evaluate the effects
      of implantation of polyetheretherketone (PEEK) cage containing synthetic bone
      particulate on the height and cross-sectional area of the foramen, the
      intervertebral disk height and the degree of lordosis. METHODS: Twenty
      consecutive patients with radiculopathy owing to cervical disk herniation were
      scheduled. They underwent multislice computed tomographic scanning pre
      operatively and 1 day post-operatively. RESULTS: Pre-operatively, the mean height
      of the right foramina was 8.807 +/- 1.120 mm, the left foramina was 9.500 +/-
      1.529 mm. Post-operatively, the mean foraminal height of the right side was
      11.080 +/- 1.121 mm and 10.020 +/- 1.453 mm on the left. This difference reached
      statistical significance on the right foraminal height (p=0.000) but not on the
      left side (p=0.078). The mean area of the right foramina was 46.82 +/- 14.54
      mm(2) and 52.71 +/- 15.62 mm(2) on the left side pre-operatively. Post
      operatively, the values were 60.87 +/- 15.91 mm(2) and 55.83 +/- 13.88 mm(2)
      respectively. In terms of pre-operative value, the 1 day post-operative
      measurement reached again statistical significance (p=0.002) on the right side.
      The mean value of disk height was 3.653 +/- 0.596 mm pre-operatively and 6.387 +/
      0.533 mm at 1 day post-operatively. This difference is statistically significant
      (p=0.000). DISCUSSION: Implantation of a PEEK cage containing synthetic bone
      particulate in the treatment of cervical disk disease offers good immediate
      stabilization by easier implantation technique and avoids donor site morbidity.
      It provides an increase in height and cross-sectional area of the neural
      foramina. These preliminary results suggest that interbody fusion cages appear to
      be safe and effective.

PMID- 16808892
TI  - Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin
      resistance.
AB  - Type 2 diabetes is characterized by cellular and extracellular Mg depletion.
      Epidemiologic studies showed a high prevalence of hypomagnesaemia and lower
      intracellular Mg concentrations in diabetic subjects. Insulin and glucose are
      important regulators of Mg metabolism. Intracellular Mg plays a key role in
      regulating insulin action, insulin-mediated-glucose uptake and vascular tone.
      Reduced intracellular Mg concentrations result in a defective tyrosine-kinase
      activity, post-receptorial impairment in insulin action, and worsening of insulin
      resistance in diabetic patients. Mg deficit has been proposed as a possible
      underlying common mechanism of the "insulin resistance" of different metabolic
      conditions. Low dietary Mg intake is also related to the development of type 2
      diabetes. Benefits of Mg supplementation on metabolic profile in diabetic
      subjects have been found in most, but not all clinical studies, and larger
      prospective studies are needed to support the potential role of dietary Mg
      supplementation as a possible public health strategy in diabetes risk.

PMID- 16808893
TI  - Ceramide 1-phosphate/ceramide, a switch between life and death.
AB  - Ceramide is a well-characterized sphingolipid metabolite and second messenger
      that participates in numerous biological processes. In addition to serving as a
      precursor to complex sphingolipids, ceramide is a potent signaling molecule
      capable of regulating vital cellular functions. Perhaps its major role in signal
      transduction is to induce cell cycle arrest, and promote apoptosis. In contrast,
      little is known about the metabolic or signaling pathways that are regulated by
      the phosphorylated form of ceramide. It was first demonstrated that ceramide-1
      phosphate (C1P) had mitogenic properties, and more recently it has been described
      as potent inhibitor of apoptosis and inducer of cell survival. C1P and ceramide
      are antagonistic molecules that can be interconverted in cells by kinase and
      phosphatase activities. An appropriate balance between the levels of these two
      metabolites seems to be crucial for cell and tissue homeostasis. Switching this
      balance towards accumulation of one or the other may result in metabolic
      dysfunction, or disease. Therefore, the activity of the enzymes that are involved
      in C1P and ceramide metabolism must be efficiently coordinated to ensure normal
      cell functioning.

PMID- 16808894
TI  - Structure-activity relationship study of the cell-penetrating peptide pVEC.
AB  - The peptide pVEC is a recently described cell-penetrating peptide, derived from
      the murine vascular endothelial-cadherin protein. In order to define which part
      of this 18-amino acid long peptide is important for the cellular translocation,
      we performed a structure-activity relationship study of pVEC. Together with the l
      alanine substituted peptides, the retro-pVEC, D-pVEC and the scramble pVEC are
      studied for comparison. The peptide analogues are labeled with carboxyfluorescein
      at the N-terminus for monitoring the cellular uptake into human Bowes melanoma
      cells with different efficacy. We show that all the Fl-pVEC analogues internalize
      in live Bowes melanoma cells. l-Alanine substitution of the five respective N
      terminal hydrophobic amino acids significantly decreases the translocation
      property, while replacing of Arg(6), Arg(8) or Ser(17) by alanine enhances the
      uptake. The uptake of pVEC is significantly reduced by treatment with an
      endocytosis inhibitor wortmannin. Treatment with heparinase III, nystatin and
      EIPA had no effect on the peptide uptake. The data presented here show that the N
      terminal hydrophobic part of pVEC is crucial for efficient cellular
      translocation.

PMID- 16808895
TI  - The reinforcing effect of contingent attention on verbal perseverations of two
      children with severe visual impairment.
AB  - The frequency of verbal perseverations of two children with severe visual
      impairment was reduced using differential reinforcement of appropriate speech
      coupled with extinction of perseverative utterances. A reversal design in which
      baseline and intervention were alternated in an A-B-A-B sequence was employed to
      show the functional relationship between the target behaviors and the treatment
      procedure. There was a marked increase in appropriate utterances and a correlated
      decrease in perseverative ones. These findings suggest that this singular feature
      of the language of certain children with visual impairment is, under natural
      conditions, probably maintained by the attention provided by their caregivers.

PMID- 16808896
TI  - Automatic transcription factor classifier based on functional domain composition.
AB  - To understand the transcriptional regulatory mechanism, it is indispensable to
      identify transcription factors (TF) from the whole genome and to classify
      transcription factors into different classes. New computational approaches have
      been developed to identify TFs/non-TFs, and furthermore to classify TFs into four
      different classes, based on the protein functional domain composition [K.C. Chou,
      Y.D. Cai, Using functional domain composition and support vector machines for
      prediction of protein subcellular location, J. Biol. Chem. 277 (2002) 45765
      45769]. We trained and tested our method on a non-redundancy dataset consisting
      of 74 transcription factors collected from TRANSFAC v7.0 [V. Matys, O.V. Kel
      Margoulis, E. Fricke, I. Liebich, S. Land, A. Barre-Dirrie, I. Reuter, D.
      Chekmenev, M. Krull, K. Hornischer, N. Voss, P. Stegmaier, B. Lewicki-Potapov, H.
      Saxel, A.E. Kel, E. Wingender, TRANSFAC(R) and its module TRANSCompel(R):
      transcriptional gene regulation in eukaryotes, Nucleic Acids Res. 34 (2006) D108
      D110] and 1558 non-transcription factors from UniProtKB/Swiss-Prot Release 49.3
      of 21-Mar-2006. The overall success rates of jackknife cross-validation tests
      reached 98.4% for TF/non-TF identification and 97.2% for classifications of TF
      classes: basic domains, zinc-coordinating DNA-binding domains, helix-turn-helix,
      and beta-scaffold factors.

PMID- 16808897
TI  - Silence of synaptotagmin I in INS-1 cells inhibits fast exocytosis and fast
      endocytosis.
AB  - Synaptotagmin I (Syt I) is a Ca(2+) sensor for triggering fast synchronized
      release of neurotransmitters. However, controversy remains whether Syt I is also
      obligatory for the exocytosis and endocytosis of larger dense core vesicles
      (LDCVs) in endocrine cells. In this study, we used a short hairpin RNA (shRNA) to
      silence the expression of Syt I and investigated the roles of Syt I on exocytosis
      and endocytosis in INS-1 cells. Our results demonstrated that expression of Syt I
      is remarkably reduced by the Syt I gene targeting shRNA. Using high-time
      resolution capacitance measurement, we found that the silence of Syt I decreased
      the calcium sensitivity of fusion of insulin granules and therefore reduced the
      exocytotic burst triggered by step-like [Ca(2+)](i) elevation. In addition, the
      occurrence frequency and amplitude of fast endocytosis were remarkably reduced in
      the silenced cells. We conclude that Syt I not only participates in the Ca(2+)
      sensing of LDCV fusion with plasmalemma, but also plays a crucial role in fast
      endocytosis in INS-1 cells.

PMID- 16808898
TI  - Glutathione peroxidase 3 of Saccharomyces cerevisiae regulates the activity of
      methionine sulfoxide reductase in a redox state-dependent way.
AB  - Glutathione peroxidase (Gpx) is one of the most important anti-oxidant enzymes in
      yeast. Gpx3 is a ubiquitously expressed isoform that modulates the activities of
      redox-sensitive thiol proteins, particularly those involved in signal
      transduction pathways and protein translocation. In order to search for the
      interaction partners of Gpx3, we carried out immunoprecipitation/2-dimensional
      gel electrophoresis (IP-2DE), MALDI-TOF mass spectrometry, and a pull down assay.
      We found that Mxr1, a peptide methionine sulfoxide reductase, interacts with
      Gpx3. By reducing methionine sulfoxide to methionine, Mxr1 reverses the
      inactivation of proteins caused by the oxidation of critical methionine residues.
      Gpx3 can interact with Mxr1 through the formation of an intermolecular disulfide
      bond. When oxidative stress is induced by H(2)O(2), this interaction is
      compromised and the free Mxr1 then repairs the oxidized proteins. Our findings
      imply that this interaction links redox sensing machinery of Gpx3 to protein
      repair activity of Mxr1. Based on these results, we propose that Gpx3 functions
      as a redox-dependent exquisite regulator of the protein repair activity of Mxr1.

PMID- 16808899
TI  - Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK
      activity.
AB  - Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion
      and myotube formation. However, the role of CD9 in osteoclast, another
      multinucleated cell type, is not still clear. Therefore, we investigated the role
      of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage
      cells and its expression level increased during the progression of RANKL-induced
      osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly
      suppressed RANKL-induced multinucleated osteoclast formation and the mRNA
      expression of osteoclast differentiation marker genes. To define CD9-regulated
      osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced
      long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive
      activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1
      almost completely blocked osteoclast differentiation. Taken together, these
      results suggest that CD9 expressed on osteoclast lineage cells might positively
      regulate osteoclastogenesis via the regulation of p44/42 MAPK activity.

PMID- 16808900
TI  - A novel insertion of a rearranged L1 element in exon 44 of the dystrophin gene:
      further evidence for possible bias in retroposon integration.
AB  - L1 elements are mammalian retrotransposons contributing to genome evolution and
      causing rare mutations in human. We describe a de novo insertion of an L1 element
      into the dystrophin gene resulting in skipping of exon 44 and causing Duchenne
      muscular dystrophy in a boy. The L1 element was rearranged due to the twin
      priming mechanism, but contrary to all described L1 rearrangements the 5' region
      of the inverted L1 sequence ended within the poly(A) tail of the element.
      Furthermore, the target site for the insertion was located only 87 bp from the
      insertion site in another patient described previously. These findings can
      contribute to the understanding of the mechanisms of L1 element rearrangement,
      and may support the notion that some subregions of the human genome could be
      preferred targets for retroelements using the L1 enzymatic machinery.

PMID- 16808901
TI  - Cellular tolerance of prion protein PrP in yeast involves proteolysis and the
      unfolded protein response.
AB  - Secretory proteins undergo a stringent quality control process in the endoplasmic
      reticulum (ER). Misfolded ER proteins are returned to the cytosol and destroyed
      by the proteasome. Prion protein PrP is degraded by the proteasome in mammalian
      cells. However, the significance of proteolysis on PrP-induced cell death is
      controversial. Moreover, the specific pathway involved in PrP degradation remains
      unknown. Here, we demonstrate that the unglycosylated form of human PrP is
      subjected to the ER-associated protein degradation (ERAD) process in the yeast
      Saccharomyces cerevisiae. We also show that unglycosylated PrP is degraded by the
      Hrd1-Hrd3 pathway. Accumulation of misfolded proteins triggers the unfolded
      protein response (UPR), which promotes substrate refolding. Interestingly, we
      find that the expression of PrP leads to growth impairment in cells deficient in
      UPR and ERAD. These findings raise the possibility that decreased UPR activity
      and proteolysis may contribute to the pathogenesis of some prion-related
      diseases.

PMID- 16808903
TI  - Hum-PLoc: a novel ensemble classifier for predicting human protein subcellular
      localization.
AB  - Predicting subcellular localization of human proteins is a challenging problem,
      especially when unknown query proteins do not have significant homology to
      proteins of known subcellular locations and when more locations need to be
      covered. To tackle the challenge, protein samples are expressed by hybridizing
      the gene ontology (GO) database and amphiphilic pseudo amino acid composition
      (PseAA). Based on such a representation frame, a novel ensemble classifier,
      called "Hum-PLoc", was developed by fusing many basic individual classifiers
      through a voting system. The "engine" of these basic classifiers was operated by
      the KNN (K-nearest neighbor) rule. As a demonstration, tests were performed with
      the ensemble classifier for human proteins among the following 12 locations: (1)
      centriole; (2) cytoplasm; (3) cytoskeleton; (4) endoplasmic reticulum; (5)
      extracell; (6) Golgi apparatus; (7) lysosome; (8) microsome; (9) mitochondrion;
      (10) nucleus; (11) peroxisome; (12) plasma membrane. To get rid of redundancy and
      homology bias, none of the proteins investigated here had > or = 25% sequence
      identity to any other in a same subcellular location. The overall success rates
      thus obtained via the jackknife cross-validation test and independent dataset
      test were 81.1% and 85.0%, respectively, which are more than 50% higher than
      those obtained by the other existing methods on the same stringent datasets.
      Furthermore, an incisive and compelling analysis was given to elucidate that the
      overwhelmingly high success rate obtained by the new predictor is by no means due
      to a trivial utilization of the GO annotations. This is because, for those
      proteins with "subcellular location unknown" annotation in Swiss-Prot database,
      most (more than 99%) of their corresponding GO numbers in GO database are also
      annotated with "cellular component unknown". The information and clues for
      predicting subcellular locations of proteins are actually buried into a series of
      tedious GO numbers, just like they are buried into a pile of complicated amino
      acid sequences although with a different manner and "depth". To dig out the
      knowledge about their locations, a sophisticated operation engine is needed. And
      the current predictor is one of these kinds, and has proved to be a very powerful
      one. The Hum-PLoc classifier is available as a web-server at
      http://202.120.37.186/bioinf/hum.

PMID- 16808902
TI  - Mechanisms of establishment of persistent SARS-CoV-infected cells.
AB  - Previously, we reported the establishment of cells with persistent SARS-CoV
      infection after apoptotic events and showed that both JNK and PI3K/Akt signaling
      pathways are important for persistence by treatment with inhibitors at the early
      stages of SARS-CoV infection. However, the mechanisms of establishment of
      persistent infection are still unclear. In this study, we investigated which
      signaling pathways play important roles in escape from apoptosis in cells
      infected with SARS-CoV. In persistently infected cells at 50h.p.i., PI3K/Akt,
      JNK, p38 MAPK and Bcl-2 were phosphorylated and the protein levels of Bcl-2 and
      Bcl-xL were increased. When surviving cells were treated with the JNK-specific
      inhibitor, SP600125, at 50h.p.i., all cells died, suggesting that the JNK
      signaling pathway is necessary for maintenance of persistently infected cells.
      Among the signaling pathways in persistently infected cells, Akt and JNK were
      phosphorylated in SARS-CoV-nucleocapsid (N) protein-expressing Vero E6 cells
      using vaccinia viral vector (DIs), strongly suggesting that N protein-induced
      phosphorylation of Akt and JNK are necessary to establish persistence. These
      results indicated that at least four proteins, Akt, JNK, Bcl-2 and Bcl-xL, are
      necessary for survival of persistently SARS-CoV-infected cells.

PMID- 16808904
TI  - Real-time chemiluminescent imaging and detection of reactive oxygen species
      generated in the UVB-exposed human skin equivalent model.
AB  - The objective of this study is to image and detect reactive oxygen species (ROS)
      generated in the UVB-exposed three-dimensional human skin equivalent model
      (HSEM), EpiDermtrade mark 200, because the alternative system needs to be
      urgently established as a replacement for the skin of experimental animals.
      Evidence that the ROS generation is enhanced in the skin of live animals after
      the UVB exposure was already obtained, by using the real-time chemiluminescent
      (RT-CL) method consisting of a sensitive CL probe (CLA) and an ultra-low light
      imaging apparatus. In this study, CL emission due to the reaction of CLA with
      endogenously generated ROS increased significantly in the UVB-treated HSEM
      compared with that in the intact HSEM, the maximum level being observed at a dose
      of 27mJ/cm(2). ROS under UVB exposure was identified to be ()O2- and (1)O(2) as
      observed by suppressive effects of SOD and beta-carotene topically applied on
      sample surface before the UVB exposure. The results for UVB-induced ROS
      generation in HSEM were consistent with those observed in the skin of live
      animals. HSEM combined with the RT-CL method was shown to be useful system not
      only to predict UVB-induced ROS-related skin responses in human but also to find
      protective agents against UVB-stimulated oxidative stress in place of animals and
      ex vivo human skin.

PMID- 16808905
TI  - Recruitment of TIP47 to lipid droplets is controlled by the putative hydrophobic
      cleft.
AB  - Adipose differentiation-related protein (ADRP) and TIP47 show sequence
      similarity, particularly in their N-terminal PAT-1 domain. Under standard culture
      conditions, ADRP existed in most lipid droplets (LDs), whereas TIP47 was observed
      only in some LDs and recruited to LDs on treatment with fatty acids. By analyzing
      deletion mutants, we found that the C-terminal half of TIP47, or more
      specifically the putative hydrophobic cleft [S.J. Hickenbottom, A.R. Kimmel, C.
      Londos, J.H. Hurley, Structure of a lipid droplet protein; the PAT family member
      TIP47, Structure (Camb) 12 (2004) 1199-1207.], was involved in LD targeting and
      responsiveness to fatty acids. The result contrasted with that observed for ADRP
      and implied a distinct LD-targeting mechanism for TIP47. Consistent with this,
      overexpression of Rab18 decreased ADRP, but not TIP47, from LDs, and TIP47 did
      not displace pre-existing ADRP from LDs. But ADRP may be a factor to control the
      TIP47 behavior, because TIP47 in LDs increased upon down-regulation of ADRP. The
      results suggested that the putative hydrophobic cleft is critical for the unique
      characteristics of TIP47.

PMID- 16808906
TI  - Intrauterine growth restriction due to uteroplacental vascular insufficiency
      leads to increased hypoxia-induced cerebral apoptosis in newborn piglets.
AB  - Uteroplacental vascular insufficiency in humans is a common cause of intrauterine
      growth restriction (IUGR) and is associated with an increased incidence of
      perinatal asphyxia and neurodevelopmental disorders compared to normal weight
      newborns. Experimental models that provide an opportunity to analyze the
      pathogenesis of these relationships are limited. Here, we used neonatal pigs from
      large litters in which there were piglets of normal birth weight (for controls)
      and of low birth weight (for uteroplacental vascular insufficiency). Hypoxia was
      induced in paired littermates by reducing the fraction of inspired oxygen to 4%
      for 25 min. Brain tissue was collected 4 h post-hypoxia. Cerebral levels of
      apoptosis were quantified morphologically and verified with caspase-3 activity
      and TUNEL. Expression of Bcl-2, Bcl-XL and Bax proteins was investigated using
      immunohistochemistry. Cellular positivity for Bcl-2 was consistently higher in
      the non-apoptotic white matter of the hypoxic IUGR animals compared with their
      littermates and reached significance at P < 0.05 in several pairs of littermates.
      Alterations in Bax showed a trend towards higher expression in the hypoxic IUGR
      littermates but rarely reached significance. The IUGR piglets showed a
      significantly greater amount of apoptosis in response to the hypoxia than the
      normal weight piglets, suggesting an increased vulnerability to apoptosis in the
      IUGR piglets.

PMID- 16808907
TI  - Changes in nNOS and NADPH diaphorase in frog retina and tectum after axotomy and
      FGF-2 application.
AB  - We have shown previously that application of fibroblast growth factor-2 (FGF-2)
      to the cut optic nerve of the frog, Rana pipiens, augments the survival of
      retinal ganglion cells (RGCs). In this study, we examine the effects of axotomy
      and FGF-2 treatment upon the distribution of nitric oxide synthase (NOS) and
      NADPH diaphorase (NADPH-d) activity in the frog retina and tectum. We find that
      NOS and NADPH-d are largely absent from RGCs but present in amacrine neurons and
      in retinorecipient tectal layers. Axotomy alone has little effect on NOS
      expression or diaphorase activity, apart from slightly increasing the levels of
      expression in a subpopulation of amacrine cells that arborize in the On sublamina
      of the inner plexiform layer. FGF-2 application to the optic nerve down-regulates
      NOS expression and activity in the retina and up-regulates it in the tectum,
      particularly in retinorecipient layers. Electron microscopy of the optic nerve
      and neurofilament immunostaining of the tectum suggests that FGF-2 treatment
      increases the number of regenerating retinal axons arriving at the tectum. The
      effects in the retina and tectum are probably indirect, that in the retina being
      due to retrograde signaling from RGCs to amacrine neurons, and that in the tectum
      being due to re-induction of NOS expression in tectal neurons by the arrival of
      regenerating axons. At this stage, it appears unlikely that these changes in NOS
      play a role in the FGF-2's survival effect on RGCs.

PMID- 16808908
TI  - Abnormal Fas/FasL and caspase-3-mediated apoptotic signaling pathways of T
      lymphocyte subset in patients with systemic lupus erythematosus.
AB  - OBJECTIVES: To explore the relationships between Fas-FasL-mediated signaling
      pathway and apoptosis disturbance of T lymphocyte subset in patients with SLE.
      METHODS: Flow cytometry was used to determine the percentage of apoptotic
      lymphocytes and necrotic lymphocytes by AnnexinV-FITC/PI double staining. Cell
      surface expression rates of Fas, FasL, and intracellular expression rates of
      activated caspase-3 were evaluated by two-color flow cytometry analysis in
      peripheral T lymphocyte subsets of SLE patients with inactive disease (n=22) and
      with active disease (n=17). The serum concentration of anti-nucleosome antibodies
      in SLE patients were assayed by ELISA immunoassay methods. Health volunteers
      (n=13) served as controls. RESULTS: The percentage of early apoptotic cells was
      enhanced in patients with active disease (P=0.001, vs. control) and in patients
      with inactive disease (P=0.004, vs. control). Compared with health control, the
      percentage of necrotic cells was significant higher in patients with active
      disease (P=0.001). The percentages of CD4(+)T cells expressing Fas (P=0.023, vs.
      control) and FasL (P=0.001, vs. control) were increased in patients with active
      disease. But there were no obvious differences of expression rates of Fas and
      FasL on T cell subset between two disease groups (P>0.05). In patients with
      active disease the percentage of CD4(+)T cells or CD8(+)T cells expressing
      intracellular activated caspase-3 significantly increased compared to inactive
      disease patients (P=0.018, P=0.027, respectively) and health controls (P=0.001,
      P=0.001, respectively). The serum concentration of anti-nucleosome antibodies was
      strikingly higher in patients with active disease (P=0.002, vs. patients with
      inactive disease; P=0.001, vs. control, respectively), however, the serum
      concentration of anti-nucleosome antibodies was not obviously different between
      patients with inactive disease and health control group (P=0.473). The percentage
      of apoptotic cells correlated with the serum concentration of anti-nucleosome
      antibodies in SLE patients (r(s)=0.350, P=0.031). CONCLUSIONS: Apoptosis of T
      lymphocyte subset in SLE patients increases. CD4(+)T cells are a state of active
      apoptosis. Fas/FasL-mediated apoptotic pathways are especially important for
      CD4(+)T cells undergoing apoptosis in SLE patients with active disease. Increased
      Fas expression results in a higher susceptibility to Fas-mediated apoptosis,
      which contributes to the increased levels of intracellular activated caspase-3
      and accelerates apoptosis of T lymphocytes. The degree of lymphocytic apoptosis
      disturbance correlates with the level of anti-nucleosome antibodies in the
      circulation. Acceleration of lymphocytic apoptosis plays important roles in
      immune pathologic injury and immune regulation dysfunction.

PMID- 16808909
TI  - Argininosuccinate lyase deficiency (ASL) and carbohydrate-deficient transferrin
      (CDT): experience with four independent CDT analysis methods--misleading results
      given by the %CDT TIA assay.
AB  - BACKGROUND: Chronic liver disease can cause false-positive carbohydrate-deficient
      transferrin (CDT) results mimicking chronic alcohol abuse. We tested whether
      argininosuccinate lyase deficiency (ASL), a genetic disorder of the urea cycle
      with hepatomegaly and biochemical hepatitis, causes increased CDT results and
      whether this depends on the analytical method. METHODS: Seven serum samples from
      four ASL patients without alcohol abuse were analyzed by capillary
      electrophoresis, HPLC, particle-enhanced immunonephelometry with monoclonal CDT
      antibodies, and microcolumn CDT and non-CDT fractionation followed by a
      turbidimetric immunoassay with transferrin antibodies (%CDT TIA). RESULTS:
      Increased CDT results (two out of four patients or five out of seven samples)
      were obtained by the %CDT TIA assay, but not by the remaining three CDT tests.
      The corresponding serum samples showed increased fractions of trisialotransferrin
      by HPLC (as the IFCC reference method for CDT analysis). One sample contained an
      elevated trisialotransferrin but a normal CDT also in the %CDT TIA test. One
      patient had a normal trisialotransferrin and a normal CDT as assayed by each of
      the four CDT methods. CONCLUSIONS: Argininosuccinate lyase deficiency is not
      itself a cause for increased CDT values. Increased fractions of
      trisialotransferrin in ASL patients appear to interfere with CDT analysis by the
      %CDT TIA assay. This can give false-positive CDT results. Since this can appear
      not only in ASL patients, microcolumn CDT and non-CDT fractionation followed by a
      turbidimetric immunoassay using transferrin but not CDT antibodies by the %CDT
      TIA assay should no longer be used for CDT measurement without confirmatory
      analysis by HPLC or capillary electrophoresis.

PMID- 16808910
TI  - Computer systems analysis of spaceflight induced changes in left ventricular
      mass.
AB  - Circulatory adaptations resulting in postflight orthostasis have frequently been
      observed in response to space travel. It has been postulated that a decrement in
      left ventricular mass (LVM) found after microgravity exposure may be the central
      component in this cardiovascular deconditioning. However, a physiologic mechanism
      responsible for these changes in the myocardium has not been determined. In this
      study, we examined the sequential alterations in echocardiographic measured LVM
      from preflight to landing day and 3 days into the postflight recovery period. In
      a previous study in returning astronauts we found a comparative 9.1% reduction in
      postflight LVM that returned to preflight values by the third day of recovery.
      This data was further evaluated in a systems analysis approach using a well
      established advanced computer model of circulatory functioning. The computer
      model incorporates the physiologic responses to changes in pressures, flows and
      hydraulics within the circulatory system as affected by gravitational forces.
      Myocardial muscle progression to atrophy or hypertrophy in reaction to the
      circulatory load conditions is also included in the model. The integrative
      computer analysis suggests that these variations in LVM could be explained by
      simple fluid shifts known to occur during spaceflight and can reverse within a
      few days after reentry into earth's gravity. According to model predictions, the
      reductions in LVM found upon exposure to microgravity are a result of a
      contraction of the myocardial interstitial fluid space secondary to a loss in the
      plasma volume. This hypothesis was additionally supported by the published ground
      based study in which we followed the alterations in LVM and plasma volume in
      normal subjects in which hypovolemia was induced by simple dehydration. In the
      hypovolemic state, plasma volume was reduced in these subjects and was
      significantly correlated with echocardiographic measurements of LVM. Based on
      these experimental findings and the performance of the computer systems analysis
      it appears that reductions in LVM observed after spaceflight may be secondary to
      fluid exchanges produced by common physiologic mechanisms. Reductions in LVM
      observed after microgravity exposure have been previously postulated to be a
      central component of spaceflight-induced cardiovascular deconditioning. However,
      a recent study has demonstrated a return of astronauts' LVM to preflight values
      by the third day after landing through uncertain mechanisms. A systems analysis
      approach using computer simulation techniques allows for a dissection of the
      complex physiologic control processes and a more detailed examination of the
      phenomena. From the simulation studies and computer analysis it appears that
      microgravity induced reductions in LVM may be explained by considering
      physiologic fluid exchanges rather than cardiac muscle atrophy.

PMID- 16808911
TI  - Methylmercury interaction with lymphocyte cholinergic muscarinic receptors in
      developing rats.
AB  - Cerebral cholinergic muscarinic receptors (MR) have been suggested as one of the
      sensitive biochemical endpoints of the central nervous system altered by
      developmental exposure to the widespread seafood contaminant methylmercury
      (MeHg). In adult rats, MeHg has been shown to alter MR binding both in the brain
      and lymphocytes, supporting the use of MR in blood cells as a surrogate marker of
      CNS changes. The effects of MeHg have been evaluated on rat lymphocyte MR binding
      (using [3H]QNB as specific muscarinic ligand) in vivo (after perinatal exposure)
      and in vitro. For comparison, in vitro studies were also performed on human
      lymphocytes. Exposure to 1 mg MeHg/kg/day during pregnancy and lactation (from
      GD7 to PND7) significantly enhanced lymphocyte MR density in both adult and young
      rats 21 days after delivery, with a more pronounced effect in the mothers (B(max)
      increase of 139%) than in the male offspring (+49%) and female offspring (+73%)
      as compared with their respective controls (33+/-4, 41+/-8, and 37+/-4
      fmol/million cells), in accordance with the higher Hg levels detected in the
      adult blood (11.3+/-2.2 microg/mL) than in pups (1.3+/-0.4 microg/L in both
      genders). A lower MeHg dose (0.5 mg/kg/day) was without any effect on lymphocyte
      MRs. In in vitro studies, MeHg was an almost equipotent inhibitor of (3)H-QNB
      binding to rat and human lymphocyte MRs (IC50 values were 4.1+/-0.29, 5.2+/-0.51,
      and 5.0+/-0.9 microM for total rat lymphocytes, rat T lymphocytes, and total
      human lymphocytes, respectively). Notably, the IC50 values for MeHg to lymphocyte
      MRs were comparable to the Hg levels reached in blood (5-50 microM) of the PND21
      rats exposed to MeHg. The finding that the MR binding is a target for the effects
      of MeHg in peripheral blood cells is in accordance with our previous data in
      brain [Coccini et al., 2006. Effects of developmental co-exposure to
      methylmercury and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) on cholinergic
      muscarinic receptors in rat brain. Neurotoxicology, in press], and supports the
      use of this peripheral endpoint as a biomarker of MeHg-induced cerebral
      muscarinic alterations. The similarity of MeHg IC50 binding data between human
      and rat in peripheral tissues suggests the possible application of such biomarker
      to humans exposed to environmental chemicals.

PMID- 16808912
TI  - Blood pressure variability, baroreflex sensitivity and organ damage in
      spontaneously hypertensive rats treated with various antihypertensive drugs.
AB  - Besides blood pressure, blood pressure variability and baroreflex sensitivity
      maybe important factors determining organ damage in hypertension. This study was
      designed to investigate the effects of various antihypertensive drugs on blood
      pressure and blood pressure variability reductions, baroreflex sensitivity, and
      target organ damage in spontaneously hypertensive rats (SHR). The dose is 20
      mg/kg/day for atenolol, and 10 mg/kg/day for nifedipine, irbesartan and
      hydrochlorothiazide. We used relatively low doses of drugs to avoid a very
      remarkable normalization of blood pressure in the treatment, which would make it
      much difficult to distinguish the contribution of blood pressure variability and
      baroreflex sensitivity to organ protection from that of blood pressure. Drugs at
      the aforementioned doses were mixed into rat chow. SHR were treated for 4 months.
      Blood pressure was then continuously recorded for 24 h. After the determination
      of baroreflex sensitivity, rats were killed for organ-damage evaluation. It was
      found that long-term treatment with atenolol, nifedipine, irbesartan or
      hydrochlorothiazide all markedly reduced blood pressure variability, enhanced
      baroreflex sensitivity, and produced significant organ protection. Compared with
      blood pressure level, blood pressure variability and baroreflex sensitivity
      values showed a much closer or similar relationship with organ-damage parameters
      in every treatment group of rats. Multiple-regression analysis showed that the
      decrease in left ventricular hypertrophy, the decrease in aortic hypertrophy and
      the amelioration in renal lesion were all most closely correlated with the
      increase in baroreflex sensitivity and the decrease in systolic blood pressure
      variability. In conclusion, long-term treatment with atenolol, nifedipine,
      irbesartan or hydrochlorothiazide produced organ protection in SHR. Besides the
      blood pressure reduction, the decrease in blood pressure variability and the
      restoration of baroreflex sensitivity may contribute to this organ protection.

PMID- 16808913
TI  - Ameliorating human diabetic neuropathy: lessons from implanting hematopoietic
      mononuclear cells.

PMID- 16808915
TI  - Matrix metalloproteinases--a conceptional alternative for disease-modifying
      strategies in ALS/MND?

PMID- 16808914
TI  - Novel object recognition in Apoe(-/-) mice improved by neonatal implantation of
      wild-type multipotential stromal cells.
AB  - Multipotential bone marrow stromal cells (MSCs) from wild-type (Wt) or
      apolipoprotein E deficient (Apoe(-/-)) mice were implanted into the cerebral
      ventricles of Apoe(-/-) mice. MSCs from Wt mice continued expressing apoE up to 6
      months after implantation and were associated with enhanced novel object
      recognition and increased microtubule-associated protein 2 (MAP2)
      immunoreactivity in the dentate gyrus. These data show that MSCs can be used to
      distinguish developmental from post-developmental effects of a gene knockout and
      support their therapeutic potential for neurodegenerative diseases.

PMID- 16808916
TI  - Postural responses to multidirectional stance perturbations in cerebellar ataxia.
AB  - Previous studies of patients with focal cerebellar damage underscored the
      importance of the cerebellum for balance control. These studies were restricted
      to postural control in the pitch plane, and focused mainly on leg muscle
      responses. Here, we examined the effect of degenerative cerebellar lesions on
      postural control in multiple directions, and studied how such lesions affect
      intersegmental coordination of the legs, trunk and arms. We formulated two main
      questions. (a) Do patients with cerebellar ataxia predominantly have balance
      problems in the sagittal or frontal planes? (b) Is instability in cerebellar
      ataxia associated with increased joint motion or with reduced joint motion? We
      selected nine patients with autosomal dominant spinocerebellar ataxia (SCA)-
      three with pure ataxia and six with mild extra-cerebellar features--and 12
      matched controls. Upright standing subjects received support surface rotations
      (7.5 degrees at 60 degrees /s) that were randomly delivered in eight different
      directions of pitch or roll. We used full body kinematics to determine
      displacements of the center of mass (COM) and of individual body segments. We
      also collected surface EMG from 10 leg, trunk and arm muscles. Primary variables
      of interest were COM displacement and trunk control (angles and muscle
      responses). Secondary analyses focused on angles and muscle responses of the legs
      and arms. COM analysis demonstrated that SCA patients had greatest instability
      following backward and laterally directed perturbations. Major factors in causing
      this instability were, first, a marked reduction of stimulus-induced knee flexion
      and, second, excessive "hypermetric" motion of the pelvis (in roll) and trunk (in
      pitch). Muscle responses of SCA patients were characterized by increased late
      balance correcting activity. Responses of patients with pure ataxia were
      comparable to those of patients with mild extra-cerebellar features. A main
      underlying cause of postural instability in SCA patients appears to be "locking"
      of the knees, which may reflect compensation (by reducing interaction between
      body links) or reduced vestibulocerebellar control over leg muscles. The observed
      pathophysiology is very different from that seen in other patient populations.

PMID- 16808917
TI  - Involvement of globus pallidus in the antiparkinsonian effects of adenosine A(2A)
      receptor antagonists.
AB  - An involvement of globus pallidus (GP) in the antiparkinsonian effects of A(2A)
      receptor antagonists has been proposed on the basis of the selective localization
      of A(2A) receptors on the striatopallidal pathway. In order to investigate this
      possibility, the present study evaluated rotational behavior in unilaterally 6
      hydroxydopamine-lesioned rats following infusion of the water-soluble A(2A)
      receptor antagonist SCH BT2 into GP. SCH BT2 (5 microg/1 microl) altered neither
      motor behavior nor produced postural asymmetry by itself. However, when infused
      concomitantly with a parenteral subthreshold dose of l-DOPA (3 mg/kg i.p.)
      capable of inducing modest contralateral rotational behavior (34.7 +/- 20.7/1 h),
      SCH BT2 significantly potentiated the number of contraversive rotations (167.4 +/
      16.3/1 h). These results suggest that A(2A) receptors located in the globus
      pallidus may be involved in the antiparkinsonian effects of A(2A) antagonists.

PMID- 16808918
TI  - A normalised scale for structural genomics target ranking: the OB-Score.
AB  - Target selection and ranking is fundamental to structural genomics. We present a
      Z-score scale, the "OB-Score", to rank potential targets by their predicted
      propensity to produce diffraction-quality crystals. The OB-Score is derived from
      a matrix of predicted isoelectric point and hydrophobicity values for
      nonredundant PDB entries solved to <or=3.0 A against a background of UniRef50. A
      highly significant difference was found between the OB-Scores for TargetDB test
      datasets. A wide range of OB-Scores was observed across 241 proteomes and within
      7868 PfamA families; 73.4% of PfamA families contain >or=1 member with a high OB
      Score, presenting favourable candidates for structural studies.

PMID- 16808919
TI  - High-throughput biomonitoring of dioxins and polychlorinated biphenyls at the sub
      picogram level in human serum.
AB  - We report on the use of a state-of-the-art method for the measurement of selected
      polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and
      polychlorinated biphenyls in human serum specimens. The sample preparation
      procedure is based on manual small size solid-phase extraction (SPE) followed by
      automated clean-up and fractionation using multi-sorbent liquid chromatography
      columns. SPE cartridges and all clean-up columns are disposable. Samples are
      processed in batches of 20 units, including one blank control (BC) sample and one
      quality control (QC) sample. The analytical measurement is performed using gas
      chromatography coupled to isotope dilution high-resolution mass spectrometry. The
      sample throughput corresponds to one series of 20 samples per day, from sample
      reception to data quality cross-check and reporting, once the procedure has been
      started and series of samples keep being produced. Four analysts are required to
      ensure proper performances of the procedure. The entire procedure has been
      validated under International Organization for Standardization (ISO) 17025
      criteria and further tested over more than 1500 unknown samples during various
      epidemiological studies. The method is further discussed in terms of
      reproducibility, efficiency and long-term stability regarding the 35 target
      analytes. Data related to quality control and limit of quantification (LOQ)
      calculations are also presented and discussed.

PMID- 16808920
TI  - On-line sample preconcentration by sweeping with dodecyltrimethylammonium bromide
      in capillary zone electrophoresis.
AB  - On-line sample preconcentration of oligonucleotides with a new sweeping carrier
      was developed by using dodecyltrimethylammonium bromide (DTAB) below the critical
      micelle concentration (CMC). The sweeping results with DTAB below and above the
      CMC were compared. The use of DTAB below the CMC benefits the preconcentration of
      the oligonucleotides, while the use of DTAB above the CMC is good for hydrophobic
      small molecules. The factors affecting the sweeping results were optimized and
      this method was evaluated by constructing calibration curves for thrombin
      aptamers. The sweeping scheme produced a 112-fold sensitivity enhancement for the
      oligonucleotides relative to that run in a running buffer without DTAB. The
      sweeping method developed here can be a good reinforcement of the
      preconcentration scheme by sweeping when less-hydrophobic analytes or large
      negatively-charged molecules need to be preconcentrated.

PMID- 16808921
TI  - Hybrids of colloidal silica and waterborne polyurethane.
AB  - Waterborne polyurethane (WPU) was synthesized and followed by adding colloidal
      silica to prepare WPU-silica hybrids. The silica content in the hybrid thin films
      was varied from 0 to 50 wt%. The experimental results revealed that the viscosity
      of these hybrid solutions increased with increasing silica content and resulted
      in the aggregation of silica particle in the hybrid films. The latter result was
      evidenced by SEM examination. The effect of interaction between silica particle
      and urethane polymer chains is more significant with increasing silica content.
      The prepared hybrid films show much better thermal stability and mechanical
      properties than pure WPU. The optical transparence did not linearly decrease with
      increasing the silica fraction in the hybrid thin film. At below 20% silica
      content, the film transparence decreased with increasing silica content; the
      converse is true at above 20% silica content. These results showed that the
      prepared hybrid films demonstrated tunable transparence with the silica fraction
      in the films.

PMID- 16808922
TI  - Dendron-protected Au nanoparticles--effect of dendritic structure on chemical
      stability.
AB  - A series of gold nanoparticles stabilised by 'Newkome-type' dendritic branching
      has been synthesised and fully characterised. In particular, the properties and
      behaviour of these hybrid materials are compared with those of a previously
      reported set of nanoparticles stabilised by dendrons constructed using l-lysine
      building blocks. The rates of cyanide-induced nanoparticle decomposition were
      determined, and it was found that the rate of decomposition increased on the
      introduction of dendritic branching. Furthermore, 'Newkome-type' dendrons were
      significantly more effective at protecting the encapsulated gold nanoparticle
      than the l-lysine based dendrons. It is proposed that this observation can be
      explained on the basis of more effective packing and surface coverage by the
      'Newkome-type' dendrons. Importantly, this study therefore demonstrates that the
      organic chemical structure of dendritic ligands plays a crucial role in
      controlling the reactivity of self-assembled hybrid nanostructures.

PMID- 16808923
TI  - Characterization of Langmuir and Langmuir-Blodgett films of a thiomacrocyclic
      ionophore by surface pressure and AFM.
AB  - The new synthesized thiomacrocyclic ionophore 4-phenyl-4-sulfide-11-(1-oxodecyl)
      1,7-dithia-11-aza-4-phosphacyclotetradecane has proven to form Langmuir and
      Langmuir-Blodgett (LB) films. This ionophore shows a large affinity for
      copper(II) ions. Thus, the influence of the subphase composition on the surface
      pressure-area isotherms has been studied. The LB films have been observed by AFM
      and the effect of the subphase composition and the deposition surface pressure on
      the LB films is discussed. AFM image morphology has been correlated to the
      ionophore molecular structure. Surface pressure-area isotherms and AFM images
      show that the presence of copper(II) ions has an important role in the film
      structure.

PMID- 16808924
TI  - A common representational system governed by Weber's law: nonverbal numerical
      similarity judgments in 6-year-olds and rhesus macaques.
AB  - This study compared nonverbal numerical processing in 6-year-olds with that in
      nonhuman animals using a numerical bisection task. In the study, 16 children were
      trained on a delayed match-to-sample paradigm to match exemplars of two anchor
      numerosities. Children were then required to indicate whether a sample
      intermediate to the anchor values was closer to the small anchor value or the
      large anchor value. For two sets of anchor values with the same ratio, the
      probability of choosing the larger anchor value increased systematically with
      sample number, and the psychometric functions superimposed when plotted on a
      logarithmic scale. The psychometric functions produced by the children also
      superimposed with the psychometric functions produced by rhesus monkeys in an
      analogous previous experiment. These examples of superimposition demonstrate that
      nonverbal number representations, even in children who have acquired the verbal
      counting system, are modulated by Weber's law.

PMID- 16808925
TI  - Morphological knowledge as revealed in children's spelling accuracy and reports
      of spelling strategies.
AB  - The goal of the current research was to assess whether children can make
      strategic use of morphological relations among words to spell. French-speaking
      children in Grade 4 spelled three word types: (a) phonological words that had
      regular phoneme-grapheme correspondences, (b) morphological words that had silent
      consonant endings for which a derivative revealed the silent ending, and (c)
      lexical words that had silent consonant endings for which no familiar derivative
      revealed the ending. Children were also asked to provide immediate retrospective
      reports of the strategies used to spell each word. Two experiments (Ns = 46 and
      39) were conducted. As expected, children in Grade 4 spelled phonological words
      more accurately than they did words with silent consonant endings. In addition,
      children spelled morphological words more accurately than they did lexical words.
      Reports of using retrieval were associated with accurate performance across word
      types. Importantly, reports of using morphological strategies to spell
      morphological words were associated with a similar level of accuracy, as were
      reports of using retrieval. Even though children reported using a phonological
      strategy frequently across all word types, this strategy was associated with
      accurate performance only for spelling phonological words. Experiment 2
      replicated the results of Experiment 1 with another set of stimuli and also
      showed that children's morphological awareness predicted their spelling accuracy
      for morphological words as well as the reported frequency of morphological
      strategy use. In sum, the findings revealed that most children showed evidence of
      adaptive strategy use.

PMID- 16808926
TI  - Energetics of emergence in the cicadas, Cyclochila australasiae and Abricta
      curvicosta (Homoptera: Cicadidae).
AB  - The final moult in cicadas marks a major transition in lifestyle and is a
      behaviour that makes the cicada vulnerable to predation. Consequently, emergence
      times are short and, we predict, therefore the rate of energy consumption would
      be high. Hence, we measured the energetic cost of emergence in Cyclochila
      australasiae (green grocer) and Abricta curvicosta (floury baker) cicadas during
      the final moult from nymph to adult cicada. Maximum energy expended whilst
      emerging was compared between the sexes and species. Even though C. australasiae
      take longer to emerge than A. curvicosta, the mass-specific cost of emergence is
      not different between the two species (C. australasiae: 11.34+/-2.55 J g(-1); A.
      curvicosta: 12.91+/-1.90 J g(-1)). The mass-specific metabolic rates of fully
      emerged adults of both species are approximately twice those of the nymphs and
      the maximum metabolic rate during emergence is about 1.5 times higher than the
      resting metabolic rate of emerged adults. Emergence times, as indicated by rates
      of oxygen consumption, are longer than expected and probably reflect limitations
      in the oxygen capacity of the cicadas during moulting.

PMID- 16808927
TI  - Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and
      adjustment disorder with anxious mood: a randomized, double-blind, placebo
      controlled trial.
AB  - Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive
      functioning and stabilizes mood in cognitively impaired elderly subjects.
      Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with
      mental decline, therefore it was now tested for clinical efficacy in younger
      patients suffering from anxiety. One hundred and seven patients with generalized
      anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM,
      n=25) according to the diagnostic and statistical manual of mental disorders,
      third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb
      761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses
      were performed on the primary outcome measure, the Hamilton rating scale for
      anxiety (HAMA), and the secondary variables, the clinical global impression of
      change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the
      list of complaints (B-L'), and the patient's global rating of change. The HAMA
      total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the
      high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively.
      Changes were significantly different from placebo for both treatment groups with
      p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a
      dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on
      all secondary outcome measures. It was safe and well tolerated and may thus be of
      particular value in elderly patients with anxiety related to cognitive decline.

PMID- 16808928
TI  - Genetic code from tRNA point of view.
AB  - The possible codon-anticodon pairings follow the standard genetic code, yet in a
      different mode. The corresponding rules for decoding sequence of the codons in
      mRNA with tRNA may be called "tRNA code". In this paper we analyse the mutational
      and translational stability of such tRNA code. Our approach is based on the model
      of "ambiguous intermediate" and on the study of underlying block structure and
      Eulerean graph technique. It is shown that the wobble rules and the reduced
      number of tRNA anticodons strongly affect the mutational and translational
      stability of the code. The selection of tRNA anticodons, besides the optimization
      of translation, also ensures the more reliable start and, to a lesser extent, the
      stop of translation. The attribution of tRNA anticodons to the groups [WWW, WWS,
      SWW, SWS] and [SSS, SSW, WSS, WSW] as well as [MMM, MMK, KMM, KMK] and [KKK, KKM,
      MKK, MKM] clearly correlates with class I and class II aminoacyl-tRNA synthetases
      and obeys the principle of the optimal coding in both cases. Both W-S and M-K
      groupings also refer to the encoding of amino acids with the large and small side
      chain volumes, which may provide such an attribution. The higher variability of
      tRNA code agrees with the suggestions that the variations in an assignment of
      tRNA anticodons may serve as the driving force generating the different variants
      of the genetic code.

PMID- 16808929
TI  - Modelling in vitro lung branching morphogenesis during development.
AB  - It has been shown experimentally that lung epithelial explants have an ability to
      undergo branching morphogenesis without mesenchyme. However, the mechanisms of
      this phenomenon remain to be elucidated. In the present study, we construct a
      mathematical model that can reproduce the dynamics of in vitro branching
      morphogenesis. We show that the system is essentially governed by three variables
      -c(0) which is the initial fibroblast growth factor (FGF) concentration, D which
      is the diffusion coefficient of FGF, and beta which describes the mechanical
      strength of the cytoskeleton. It is confirmed by numerical simulations that this
      model can reproduce the experimentally obtained patterns qualitatively. Finally,
      we experimentally verify two predictions from the model: effects of very high FGF
      concentration and effects of small mechanical contributions of the cytoskeleton.
      The theoretical predictions match well with the experimental results.

PMID- 16808930
TI  - The nociceptive response of stressed and lithium-treated rats is differently
      modulated by different flavors.
AB  - Pleasant and unpleasant flavors and odors can modulate pain perception, and the
      efficacy of sweet flavors in reducing pain seems to be related to its hedonic
      value. Chronic variate stress paradigm is a model of depression, and is suggested
      to induce anhedonia. We observed previously that lithium may prevent behavioral
      and neurochemical alterations induced by chronic stress; so we hypothesized that
      chronically stressed animals may present different nociceptive response to
      pleasant and unpleasant tastes that could be prevented by lithium treatment.
      Adult male Wistar rats were divided into four groups, control and stressed,
      treated or not with lithium. A Chronic Variate Stress paradigm was used, and
      lithium was added to the chow. After 40 days of treatment, the tail flick latency
      of the animals was evaluated, and rats were immediately placed in a box with
      access to a 5% acetic acid solution (acid flavor). After 5 min, tail flick
      latency was measured again. On the following day, animals were submitted to the
      same procedure, with the substitution of acetic acid by condensed sweet milk
      (sweet flavor). The stressed group was the only group who did not present
      analgesia after sweet taste exposition. All groups, except the control group,
      presented increased tail flick latency after exposition to the acid flavor. These
      results indicate that pleasant and unpleasant flavors present different relevance
      for the induction of antinociception in stressed animals, and the absence of
      sweet flavor-induced analgesia may represent an anhedonic effect of the chronic
      variate stress paradigm. On the other hand, perception of different flavors may
      be more prominent in animals treated with lithium.

PMID- 16808931
TI  - Analysis of defensive responses activated by volatile allo-ocimene treatment in
      Arabidopsis thaliana.
AB  - Since volatile allo-ocimene enhances resistance of Arabidopsis thaliana against
      Botrytis cinerea, we attempted to dissect the factors involved in this induced
      resistance. The penetration of B. cinerea hyphae into Arabidopsis epidermis and
      the growth of hyphae after penetration were suppressed on allo-ocimene-treated
      leaves. allo-Ocimene also induced lignification on cell walls and veins of the
      leaves. The treatment induced accumulation of antifungal substances including the
      Arabidopsis phytoalexin, camalexin. Induction of lignification and accumulation
      of camalexin elicited by B. cinerea infection on Arabidopsis leaves after
      treating with allo-ocimene was faster and more intense than that observed with
      the leaves that had not been treated with this volatile. This suggested that allo
      ocimene could prime defensive responses in Arabidopsis. allo-Ocimene enhanced
      resistance against B. cinerea in an ethylene resistant mutant (etr1-1), a
      jasmonic acid resistant mutant (jar1-1) and a salicylic acid resistant mutant
      (npr1-1). Thus, it is suggested that a signaling pathway independent for ETR1,
      JAR1 and NPR1 was operative to induce the resistance. The series of responses
      observed after allo-ocimene-treatment was mostly similar to that observed after
      C6-aldehyde-treatment. The effect of C6-aldehyde-treatment has been largely
      accounted to the chemical reactivities of the compounds; however, from this
      result it can be suggested that resistance responses of Arabidopsis could be
      induced by the volatiles mostly independent on their reactivities and that a
      common signaling pathway unaffected by the reactivities of compound was activated
      by the volatiles.

PMID- 16808932
TI  - Nutritional content of fresh, bee-collected and stored pollen of Aloe greatheadii
      var. davyana (Asphodelaceae).
AB  - Aloe greatheadii var. davyana is the most important indigenous South African bee
      plant. Fresh, bee-collected and stored pollen of this aloe was collected and
      analysed for its nutritional content, including amino acid and fatty acid
      composition. Highly significant differences were found between the three types of
      pollen. Collection and storage by the bees resulted in increased water (13-21%
      wet weight) and carbohydrate content (35-61% dry weight), with a resultant
      decrease in crude protein (51-28% dry weight) and lipid content (10-8% dry
      weight). Essential amino acids were present in equal or higher amounts than the
      required minimum levels for honeybee development, with the exception of
      tryptophan. Fatty acids comprised a higher proportion of total lipid in fresh
      pollen than in bee-collected and stored pollen. This study is the first to
      compare the changes that occur in pollen of a single species after collection by
      honeybees.

PMID- 16808933
TI  - Constituents of Chrysothamnus viscidiflorus.
AB  - A phytochemical investigation of the aerial parts of Chrysothamnus viscidiflorus
      var. viscidiflorus afforded three new [chrysothol (1), 2 and 4] and seven known
      compounds, including five sesquiterpenes, two cinnamic acid derivatives, two
      ketoalcohol derivatives and one coumarin glucoside. The structures of two
      previously reported compounds, 1b and 1c, were revised on the basis of chemical
      reaction. Structures of the compounds were determined by extensive NMR studies,
      including DEPT, COSY, NOE, HMQC, HMBC and X-ray analysis. The unpublished X-ray
      data of the known compounds 6 and 7 are reported. Compounds chrysothol (1), and 8
      10 showed anti-cancer activity against human breast cancer cells.

PMID- 16808934
TI  - OsBLE3, a brassinolide-enhanced gene, is involved in the growth of rice.
AB  - Brassinosteroids (BRs) are a group of plant hormones involved in a wide range of
      plant growth and developmental processes. To investigate the mechanism of BR
      action in monocots, a brassinolide (BL) upregulated gene designated OsBLE3 was
      identified, cloned and characterized in rice. It was mainly expressed in roots
      and leaf sheaths with levels of expression directly dependent on the dose of BL.
      In situ hybridization detected OsBLE3 mRNA in the shoot apical meristem, organ
      primordia and vascular tissue. Furthermore, its expression was enhanced by co
      treatment with BL and low concentrations of IAA. These results, and the existence
      of auxin response elements in the 5'-flanking region of the OsBLE3 gene, indicate
      that OsBLE3 expression is under control of both BR and auxin. The GUS reporter
      gene driven by a 2277 bp OsBLE3 putative promoter was mainly expressed in
      vascular tissues, branch root primordia and was responsive to exogenous BL
      treatment. OsBLE3 transcript levels were greatly reduced in brd1 plants, a BL
      deficient mutant, compared to the wild type control. In OsBRI1 antisense
      transgenic rice and OsBLE3, the BR-insensitive mutant expression of OsBLE3 in
      response to exogenous BL treatment was significantly lower compared to that in
      control plants transformed with a vacant vector. Reduced OsBLE3 expression and
      growth retardation was also observed in OsBLE3 antisense transgenic rice plants.
      Internode cell length of the OsBLE3 antisense transgenic lines was about 70% of
      that in the vacant vector transformed control lines. These results suggest that
      OsBLE3 is involved in cell elongation in rice through dual regulation by BL and
      IAA.

PMID- 16808935
TI  - Benzoic acid allopyranosides from the bark of Pseudolarix kaempferi.
AB  - Two benzoic acid allopyranosides, pseudolaroside A and pseudolaroside B, along
      with seven known compounds were isolated from the bark of Pseudolarix kaempferi.
      Their structures were determined by analysis of HR-ESI-MS, 1D and 2D NMR
      spectroscopic data, chemical analysis and comparison to the literature data.

PMID- 16808936
TI  - Modified secoiridoid from Acicarpha tribuloides and inhibition of nitric oxide
      production in LPS-activated macrophages.
AB  - Bioassay-guided fractionation of Acicarpha tribuloides Juss. resulted in the
      isolation of an uncommon non-glycosylated secoiridoid, tribulolide (1), two known
      secoiridoid glycosides named secologanic acid (2) and vogeloside (3) as well as
      two natural chromones, 6,7-dimethoxychromone (4) and 7-hydroxy-6-methoxy-chromone
      (5). Compounds 1-3 showed inhibition of nitric oxide production in
      lipopolysaccharide-activated macrophages; their activity is comparable to that of
      aminoguanidine, a classic inhibitor.

PMID- 16808937
TI  - Isotheasaponins B1-B3 from Camellia sinensis var. sinensis tea leaves.
AB  - Three saponins, isotheasaponins B1-B3, were isolated from the leaves of the tea
      plant Camellia sinensis var. sinensis, and their structures were determined to be
      theasapogenol B [beta-D-galactopyranosyl(1-->2)][beta-D-xylopyranosyl(1-->2)
      alpha-L-arabinopyranosyl(1-->3)]-beta-D-gulcopyranosiduronic acid with two acyl
      groups by spectroscopic analysis.

PMID- 16808938
TI  - The livestock photosensitizer, phytoporphyrin (phylloerythrin), is a substrate of
      the ATP-binding cassette transporter ABCG2.
AB  - Hepatogenous photosensitization occurs in livestock following damage to the liver
      or biliary apparatus that results in impaired excretion of phytoporphyrin
      (phylloerythrin), a photosensitizer. Based on earlier observations that porphyrin
      based photosensitizers are substrates of the ATP-binding cassette transporter
      ABCG2, we examined the ability of the hepatic transporters ABCB1 (P-glycoprotein)
      and ABCG2 to transport phytoporphyrin. Transport of phytoporphyrin was blocked by
      the ABCG2-specific inhibitor fumitremorgin C (FTC) in human embryonic kidney
      cells transfected with full length human ABCG2, while no transport by cells
      transfected with human ABCB1 was noted. FTC-inhibited transport of phytoporphyrin
      was also demonstrated in ABCG2-expressing LLC-PK1 pig kidney cells, consistent
      with the idea that the pig orthologue, like human ABCG2, transports the
      photosensitizer. ABCG2 expression was confirmed by immunohistochemistry in the
      hepatocytes of cow, pig and sheep livers. We conclude that phytoporphyrin is a
      substrate for ABCG2 and that the transporter is likely responsible for its
      biliary excretion.

PMID- 16808939
TI  - A simple and inexpensive container for the transport of biological specimens in
      limited resource situations.
AB  - We describe a diagnostic specimen transport container that is appropriate for
      limited resource or emergency settings. The transport container is constructed
      from polyvinyl chloride (PVC) plumbing pipe, which is readily available and
      inexpensive (US$1-2, depending on size) and has wide flexibility of size due to
      the range of PVC pipe dimensions available. The PVC transporters are durable,
      water-resistant and may be easily decontaminated. They have been adapted for the
      transport of blood culture bottles from provincial hospitals in Laos, where,
      during a 2-year period, 380 PVC tubes containing blood culture bottles were
      transported without any leakage or breakage. We have found the PVC transporter to
      be a useful and cost-efficient durable alternative that meets IATA Packing
      Instruction 650 biological transport container requirements.

PMID- 16808940
TI  - No hearing loss associated with the use of artemether-lumefantrine to treat
      experimental human malaria.
AB  - Artemisinin derivatives are becoming the first-line treatment for uncomplicated
      malaria in areas with widespread resistance to chloroquine. Although generally
      safe and well tolerated, it has been suggested from animal experiments, and more
      recently from one human study with artemether-lumefantrine, that these compounds
      are potentially neurotoxic, affecting particularly the brainstem auditory
      pathways. We report here the auditory analyses of 15 volunteers who underwent an
      experimental human malaria infection and were treated with artemether
      lumefantrine. The subjects underwent audiological examination before the start of
      the study, during infection, and after treatment. Examination included standard
      tone audiometry, high frequency tone audiometry and auditory brainstem response
      (ABR). No effects on hearing loss that were deemed to be caused by drug treatment
      were found using tone audiometry. ABR analysis similarly failed to demonstrate
      any auditory pathway damage in the volunteers after treatment. We have thus not
      found any clear evidence of a detrimental effect on the auditory system by
      artemether-lumefantrine treatment in uncomplicated malaria. Our results support
      the continued implementation of artemisinin derivatives in the fight against drug
      resistant malaria.

PMID- 16808941
TI  - Characterization of polar brevetoxin derivatives isolated from Karenia brevis
      cultures and natural blooms.
AB  - Several novel brevetoxin derivatives were isolated and identified in Karenia
      brevis cultures and natural blooms by using solid phase extraction (SPE) and
      LC/MS(MS) techniques. These analogs were more polar compared with previously
      described brevetoxins, and were poorly extractable by conventional non-polar
      solvent (chloroform) partitioning. Brevetoxin analogs were structurally confirmed
      as hydrolyzed (open A-ring) forms of brevetoxins PbTx-1, PbTx-7, PbTx-2, and PbTx
      3, and of oxidized PbTx-1 and PbTx-2. Some of these open A-ring derivatives were
      in greater abundance than their non-hydrolyzed counterparts. All were in much
      greater abundance in bloom water filtrate compared with cell-rich fractions. Open
      A-ring compounds were cytotoxic in mouse neuroblastoma (N2a) cell assay. In the
      K. brevis bloom-exposed Eastern oyster, brevetoxin metabolites with opened A
      rings were identified (e.g., open-ring cysteine-PbTx conjugates), contributing to
      their overall toxin burden.

PMID- 16808942
TI  - The efficacy of antivenom in loxoscelism treatment.
AB  - Loxoscelism or brown spider envenomation is the most important form of araneism
      in some countries and constitutes the third cause of accidents by venomous
      animals in Brazil. The treatment of Loxosceles bites is still controversial, with
      a variety of interventions proposed and tried, such as antivenom. The majority of
      clinical studies demonstrate a significant delay between a spider's bite and
      presentation for treatment, and this delay is thought to lead to an ineffective
      administration of a specific antivenom. Even in Brazil, where the antivenom
      therapy has been indicated more frequently than in other countries, there are
      still doubts about its real capacity to neutralize local and systemic effects of
      the envenomation and the ideal period for its administration. Thus, various
      studies in animal models have tried to correlate the time of envenomation with
      the application of the antivenom and the permanence of the venom in circulation
      or in dermonecrotic lesions. The purpose of this study was to evaluate the use of
      antivenom in loxoscelism treatment and to systematize the results of studies in
      animals and humans available in the last 30 years, making possible a more
      critical analysis of the efficacy of the antivenom or its therapeutic value in
      bites by spiders of the genus Loxosceles.

PMID- 16808943
TI  - Inclusions detection using Lamb waves in flexible printed circuits.
AB  - The materials used for the manufacture of flexible printed circuits are selected
      according to various characteristics: thermal and electrical behavior, moisture
      absorption, flexibility... Those are determined by the basic materials of the
      three components of the circuit, which are the conducting layer, the adhesive
      layer and the dielectric film. Such circuits have a typical thickness of about
      200 microm and are therefore an interesting solution for a great number of
      electronic applications. However, these circuits can present various defects like
      inclusions, delaminations, cracks... In this work, we are interested in the
      detection of inclusions using guided waves propagation in such structures. These
      waves also called Lamb waves have the advantage of propagating over long
      distances while informing us about the totality of the inspected volume.
      According to the range of frequencies considered and the method used for their
      generation, it is possible to make profitable use of different propagation modes.
      To serve this purpose, laser-induced thermoelastic excitation of the first
      antisymmetric Lamb waves mode is studied. The results obtained are analysed using
      signal processing methods and then compared in order to clearly highlight the
      potentialities of these guided waves for the detection of inclusions in such
      samples.

PMID- 16808944
TI  - Nonlinear interactions in elastic resonators.
AB  - This work is dedicated to nonlinear interactions in elastic resonators. It is
      supposed that a resonator wall yields locally to the inner pressure. The elastic
      wall of the resonator induces strong dispersion and dissipation of acoustic
      energy. The dispersion can significantly influence studied nonlinear interactions
      which are ineffective because the synchronous conditions are not satisfied and
      hence a coherence length is too short. In the frame of this work conditions for
      generation of subharmonics are studied on the basis of topological and numerical
      analyze. For this reason the method of local stability is applied. For
      description of nonlinear standing wave is derived modified inhomogeneous Burgers
      equation and the inhomogeneous Korteweg-de Vries-Burgers equation. These
      equations take into account thermo-viscous losses of supposed fluids, boundary
      layer losses, wall losses and dispersion effects caused by both the resonator
      wall and the acoustic boundary layer. Number of numerical solutions of these
      model equations is shown and unsteady solitary waves are investigated.

PMID- 16808945
TI  - Polydisperse particle size characterization by ultrasonic attenuation
      spectroscopy in the micrometer range.
AB  - The theoretical advantages of ultrasonic attenuation spectroscopy for particle
      size are currently not fully utilized. Especially in the region of larger
      particles, there is a lack of experimental confirmation of applicable models
      which may be used to infer particle sizes from measured attenuation spectra. With
      the present work, an attempt is made to supply experimental data, obtained with a
      commercially available ultrasonic attenuation spectrometer, and model
      calculations, which are based on the resonant scattering theory. It is shown that
      measured attenuation results for various combinations of disperse and continuous
      phase for both polydisperse emulsions and suspensions are reproducible by
      calculation. The approach is further examined for suspensions of porous
      particles. Here, the resonant scattering approach is combined with the Biot model
      for poroelasticity to obtain attenuation results with several fractions of
      titania aggregates, differing in particle size and pore diameter. The results
      indicate that the theory of resonant scattering is a valid approach if applied to
      particle size characterization in the large particle limit.

PMID- 16808946
TI  - Physics and mechanism of ultrasonic impact.
AB  - More and more experts and researchers in industry express their interest in the
      application of deformation effects of various peening techniques on the metal
      surface. This is primarily due to a relatively simple directional change in
      condition at the surface and in sub-surface layers of the material as a result of
      plastic deformation due to impulses of force caused, among other things, by
      converting ultrasonic oscillations of various impacting elements (indenters) at
      the treated surface. These effects are of a stochastic nature and their duration
      (or the time of impact) is generally measured in units of microseconds. To obtain
      relatively uniform coverage, an operator may use several treatment passes.
      However, a stochastic nature of single impacts makes it difficult to obtain a
      uniform distribution of deformations and hence surface characteristics as
      specified, in particular, by the engineering standards. We have developed the
      methods and means of implementing the ultrasonic impact and controlling its
      parameters. A fundamental distinction of the ultrasonic impact is that its
      duration is measured in the range from hundreds of microseconds to units of
      milliseconds, while the parameters responsible for the effects upon the surface
      may be adjusted according to the task. It is important to note that in the
      frequency range of processing ultrasound of up to 80 kHz this feature of the
      ultrasonic impact allows utilizing the plastic deformation region as a matched
      membrane to transmit ultrasonic oscillations and excite ultrasonic stress waves
      in the material being treated. These phenomena, in turn, initiate highly
      effective relaxation processes, plastic deformation and, as a result thereof,
      effects upon the structure and properties of the material, which are adequate to
      the task. This paper describes the theory and the results of the experimental
      investigations into the physics of the ultrasonic impact. Also, the mechanism of
      the ultrasonic impact implementation based on high-power ultrasonic transducers
      is addressed. The paper is aimed at engineers and researchers in the area of
      industrial application of high-power ultrasonics.

PMID- 16808947
TI  - The use of ultrasound to enhance the degradation of the Basic Green by cast iron.
AB  - The effect of pH, amount of cast iron and initial concentration on the removal
      ratio of Basic Green by cast iron combined with ultrasound was investigated. It
      was shown that the reduction of Basic Green was enhanced by ultrasound. In all
      combined systems, the decolorization efficiency is more than 95%, but removal
      ratio of CODcr decreased with the increasing pH or initial dye concentration and
      increased with the increase of the amount of cast iron.

PMID- 16808948
TI  - Experimental and numerical investigations on the dispersion behaviors of wedge
      waves propagating along wedges with bilinear cross sections.
AB  - Wedge waves (WW) are guided acoustic waves propagating along the tip of a wedge,
      with energy tightly confined near the apex. This study is focused on exploring
      the dispersion behaviors of WW propagating along a bilinear wedge (BW). A BW is
      wedge with a cross section of two apex angles, compared with a linear wedge (LW)
      having a single apex angle. In the literature, many studies regarding to the
      dispersion behaviors of ASF modes are reported for LW, but not for BW. In this
      study, a combined experimental and numerical stidy is used to investigate the
      dispersion behavior of WW propagating in BW's. It is found out that WW in a BW is
      a result of mode coupling between the two WW's corresponding to simple wedges
      with the two apex angles of the BW.

PMID- 16808949
TI  - Contour tracking of specularly reflecting surfaces.
AB  - The aim of the presented work is to develop an ultrasonic imaging system for
      contour detection of specularly reflecting sheet metal surfaces and surface
      contour tracking during a continuous hydroforming process. Based on certain
      design considerations in context with hardware limitations to obtain on-line
      information about the state of forming during the whole process a sparsely filled
      ultrasonic 1D transducer array has been used with a limited number of transducer
      elements, operating at 2 MHz. It has been shown before, that "2.5D-geometries"
      (surface areas with curvatures independent of one direction) could be detected
      and tracked with a sufficient accuracy (linear aperture, 10 cm width, 21
      transducers, error in sound propagation direction less than 1 mm). We now present
      the design and results of an imaging system for automated detecting and
      consecutive tracking of sheet metal surface contours during the forming process
      by means of an active contour model. To achieve a sufficient accuracy, a priori
      in process information, e.g., starting and final positions of the sheet metal,
      forming velocity, preceding instantaneous contour geometries are incorporated
      into the active model.

PMID- 16808950
TI  - Inline ultrasonic rheometry by pulsed Doppler.
AB  - This will be a discussion of the non-invasive determination of the viscosity of a
      non-Newtonian fluid in laminar pipe flow over the range of shear rates present in
      the pipe. The procedure used requires knowledge of the flow profile in and the
      pressure drop along a long straight run of pipe. The profile is determined by
      using a pulsed ultrasonic Doppler velocimeter. This approach is ideal for making
      non-invasive, real-time measurements for monitoring and control. Rheograms of a
      shear thinning gel will be presented. The operating parameters and limitations of
      the Doppler-based instrument will be discussed. The most significant limitation
      is velocity gradient broadening of the Doppler spectra near the walls of the
      pipe. This limitation can be significant for strongly shear thinning fluids
      (depending also on the ratio of beam to pipe diameter and the transducer's
      insertion angle).

PMID- 16808951
TI  - Model based analysis of piezoelectric transformers.
AB  - Piezoelectric transformers are increasingly getting popular in the electrical
      devices owing to several advantages such as small size, high efficiency, no
      electromagnetic noise and non-flammable. In addition to the conventional
      applications such as ballast for back light inverter in notebook computers,
      camera flash, and fuel ignition several new applications have emerged such as
      AC/DC converter, battery charger and automobile lighting. These new applications
      demand high power density and wide range of voltage gain. Currently, the
      transformer power density is limited to 40 W/cm(3) obtained at low voltage gain.
      The purpose of this study was to investigate a transformer design that has the
      potential of providing higher power density and wider range of voltage gain. The
      new transformer design utilizes radial mode both at the input and output port and
      has the unidirectional polarization in the ceramics. This design was found to
      provide 30 W power with an efficiency of 98% and 30 degrees C temperature rise
      from the room temperature. An electro-mechanical equivalent circuit model was
      developed to describe the characteristics of the piezoelectric transformer. The
      model was found to successfully predict the characteristics of the transformer.
      Excellent matching was found between the computed and experimental results. The
      results of this study will allow to deterministically design unipoled
      piezoelectric transformers with specified performance. It is expected that in
      near future the unipoled transformer will gain significant importance in various
      electrical components.

PMID- 16808952
TI  - Differential geometry of ray surfaces in anisotropic solids and its contribution
      to NDE: modelling and experiment.
AB  - Point-source/point-receiver techniques are one of the most widely used methods
      for nondestructive evaluation of anisotropic materials. The group velocities
      resulting from these techniques must be, for further inverse evaluation of
      elastic coefficients, geometrically converted into corresponding phase
      velocities. On the other hand, the phase velocities can be determined from a
      material's response to a line source. But, due to the anisotropy, the short line
      sources generated by cylindrical lenses are insufficient for reliable
      determination of the phase velocity. In this paper, a long line source is
      approximated by a set of linearly arranged point sources. As it follows from the
      differential geometry of ray surfaces, information obtained from such set of
      sources is sufficient for determination of phase velocities of both the quasi
      transverse and the quasi-longitudinal modes of propagation. Moreover, this
      approach can be generalized for any arbitrary set of point sources only by
      employing a proper time-base transformation. The applicability of the presented
      approaches is illustrated on transversely isotropic and tetragonal fibrous
      composite materials.

PMID- 16808953
TI  - A disk-pivot structure micro piezoelectric actuator using vibration mode B11.
AB  - Micro piezoelectric actuator using vibration mode B(11) (B(mn), where m is the
      number of nodal circles, n is the nodal diameters) is designed. Different from
      conventional wobble-type ultrasonic motor using piezoelectric rod or cylinder,
      piezoelectric disc is used to excite wobble modes and metal cylinder stator is
      used to amplify the transverse displacement, metal rod rotor is actuated to
      rotate. The outer diameter of the actuator is 14mm. There are features such as
      low drive voltage, micromation, and convenient control of wobble state by
      modifying the structure of stator, etc. Finite element analysis (FEA) of the
      stator has been made. It is found that the resonant frequency of vibration mode
      B(11) is 49.03kHz, which is measured at 45.7kHz by the laser vibrometer and
      impedance analyzer. The rotation speed has been measured, which could be as high
      as 10,071rpm under an alternating current 100V. Such piezoelectric actuator can
      be optimized and adjusted to fit practical conditions. It can be applied in the
      fields of precise instrument, bioengineering and other micro actuator system.

PMID- 16808954
TI  - Ultrasonic concentration measurement of aqueous solutions using PLS regression.
AB  - This work demonstrates the use of a multivariate statistical technique called
      partial least squares (PLS) to extract material related data by analyzing spectra
      of ultrasonic pulses. We show how PLS can be used to estimate the concentration
      of sodium chloride in an aqueous solution. The paper describes the use of PLS and
      discusses pre-processing of ultrasonic data, the PLS algorithm as well as model
      validation. The measured concentrations are compared to reference values. The
      influence of disturbances and parameter changes is highlighted. The proposed
      method is easily adaptable to similar applications and permits a cost-saving
      implementation using existing and approved hardware.

PMID- 16808955
TI  - Characterization of TRIM5alpha trimerization and its contribution to human
      immunodeficiency virus capsid binding.
AB  - The coiled-coil domain of the tripartite motif (TRIM) family protein TRIM5alpha
      is required for trimerization and function as an antiretroviral restriction
      factor. Unlike the coiled-coil regions of other related TRIM proteins, the coiled
      coil of TRIM5alpha is not sufficient for multimerization. The linker region
      between the coiled-coil and B30.2 domains is necessary for efficient TRIM5alpha
      trimerization. Most of the hydrophilic residues predicted to be located on the
      surface-exposed face of the coiled coil can be altered without compromising
      TRIM5alpha antiviral activity against human immunodeficiency virus (HIV-1).
      However, changes that disrupt TRIM5alpha trimerization proportionately affect the
      ability of TRIM5alpha to bind HIV-1 capsid complexes. Therefore, TRIM5alpha
      trimerization makes a major contribution to its avidity for the retroviral
      capsid, and to the ability to restrict virus infection.

PMID- 16808956
TI  - Specific interaction of CXCR4 with CD4 and CD8alpha: functional analysis of the
      CD4/CXCR4 interaction in the context of HIV-1 envelope glycoprotein-mediated
      membrane fusion.
AB  - We investigated possible interactions between HIV-1 receptor (CD4) and the main
      coreceptors CXCR4 and CCR5. We found that CD4 and CXCR4 coexpressed in 293T cells
      form a complex that can be immunoprecipitated with antibodies directed against
      the extracellular domain of either protein. Mutagenesis revealed that the
      CD4/CXCR4 interaction maps to two previously uncharacterized basic motifs in the
      cytoplasmic domain of CD4. HIV-1 envelope glycoprotein-mediated membrane fusion
      was found to be independent of the ability of CD4 and CXCR4 to interact, whether
      fusion was studied in a virus-cell or a cell-cell model. However, this
      interaction might explain the adaptation of HIV-1 to CXCR4 as an alternative to
      CCR5. We found that CXCR4 also interacts with the cytoplasmic domain of CD8alpha
      in a way that is similar to the CD4/CXCR4 interaction. The CD4/CXCR4 and
      CD8alpha/CXCR4 interactions may thus be involved in cellular signaling pathways
      shared by the CD4 and CD8alpha molecules.

PMID- 16808957
TI  - Feature detection and letter identification.
AB  - Seeking to understand how people recognize objects, we have examined how they
      identify letters. We expected this 26-way classification of familiar forms to
      challenge the popular notion of independent feature detection ("probability
      summation"), but find instead that this theory parsimoniously accounts for our
      results. We measured the contrast required for identification of a letter briefly
      presented in visual noise. We tested a wide range of alphabets and scripts
      (English, Arabic, Armenian, Chinese, Devanagari, Hebrew, and several artificial
      ones), three- and five-letter words, and various type styles, sizes, contrasts,
      durations, and eccentricities, with observers ranging widely in age (3 to 68) and
      experience (none to fluent). Foreign alphabets are learned quickly. In just three
      thousand trials, new observers attain the same proficiency in letter
      identification as fluent readers. Surprisingly, despite this training, the
      observers-like clinical letter-by-letter readers-have the same meager memory span
      for random strings of these characters as observers seeing them for the first
      time. We compare performance across tasks and stimuli that vary in difficulty by
      pitting the human against the ideal observer, and expressing the results as
      efficiency. We find that efficiency for letter identification is independent of
      duration, overall contrast, and eccentricity, and only weakly dependent on size,
      suggesting that letters are identified by a similar computation across this wide
      range of viewing conditions. Efficiency is also independent of age and years of
      reading. However, efficiency does vary across alphabets and type styles, with
      more complex forms yielding lower efficiencies, as one might expect from Gestalt
      theories of perception. In fact, we find that efficiency is inversely
      proportional to perimetric complexity (perimeter squared over "ink" area) and
      nearly independent of everything else. This, and the surprisingly fixed ratio of
      detection and identification thresholds, indicate that identifying a letter is
      mediated by detection of about 7 visual features.

PMID- 16808958
TI  - Alternative indicators of fecal pollution: relations with pathogens and
      conventional indicators, current methodologies for direct pathogen monitoring and
      future application perspectives.
AB  - The ecological and survival characteristics of bacterial, viral and parasitic
      pathogens vary under environmental conditions, indicating that probably no single
      indicator organism can predict the presence of all enteric pathogens for all
      types of waters and different host-associated fecal pollution. If there are true
      correlations between indicator organisms and pathogens, it is necessary to find
      out to what extent and under which circumstances these organisms can be used as
      reliable indicators of fecal pollution. Application of conventional and
      alternative fecal indicators has greatly enhanced our abilities to predict and
      reduce health risk associated with the use of surface waters. New molecular-based
      techniques have shown that combined use of conventional and alternative
      indicators for fecal pollution increases both the detection sensitivity and
      specificity of fecal pollution and associated pathogens. In this review, we,
      therefore, summarize the advantages and limitations of conventional and
      alternative fecal indicators in terms of predicting pathogen presence as well as
      current and future methodologies for direct pathogen monitoring in environmental
      waters. This manuscript is mainly focused on the relationships between microbial
      fecal indicators and the presence of pathogens, which have not previously been
      summarized yet and could nicely supplement with recent literature reviews on
      microbial source tracking.

PMID- 16808959
TI  - Radiolytic decomposition of multi-class surfactants and their biotransformation
      products in sewage treatment plant effluents.
AB  - Electron beam irradiation (EBI), as one of the most efficient advanced oxidation
      processes, was applied to the treatment of sewage treatment plant (STP) effluent,
      with the objective of evaluating the effectiveness of radiolytic decomposition of
      multi-class surfactants. Target compounds, included several high-volume
      surfactant groups, such as alkylphenol ethoxylates (APEOs) and their
      biotransformation products, linear alkylbenzene sulfonates (LAS), alkyl sulfates
      (AS), alkylether sulfates (AES), coconut diethanol amides (CDEA), alcohol
      ethoxylates (AEO) and polyethylene glycols (PEGs). EBI treatment of STP effluent
      (total concentration of APEO-derived compounds 265mugl(-1), being APE(2)C the
      most abundant by-degradation products) resulted in efficient decomposition of all
      alkylphenolic compounds; elimination of 94% longer ethoxy chain nonylphenol
      ethoxylates (NPEO, n(EO)=3-15) was obtained when 3kGy were applied. Slightly less
      efficient decomposition of short ethoxy chain oligomers (NPEO(1) and NPEO(2)) was
      observed, resulting in disappearance of about 80% of the initially present
      compounds. LC-MS analysis of treated wastewater suggested that the mechanism of
      EBI degradation of APEOs is a combination of two parallel pathways: a progressive
      shortening and oxidation of the ethoxy chain, which resulted in a formation of
      short ethoxy chain oligomers and APECs and central fission that resulted in
      formation of PEGs. Decomposition of APECs at 1kGy initially yielded APs, which
      were subsequently eliminated applying higher radiation doses. With a radiation
      dose of 2kGy about 95% of NPE(1)C and 97% of NPE(2)C were decomposed. Similar
      elimination rates were obtained for octylphenolic compounds. Radiolytic treatment
      applied was also very effective in removing PEGs formed as by-products from APEO
      degradation, as well as in decomposing other surfactants, such as linear LAS, AS
      and AES.

PMID- 16808960
TI  - Detection of technetium-99 in Ascophyllum nodosum from around the Welsh coast.
AB  - The presence of the radionuclide (99)Tc in the marine environment is of concern
      to environmental scientists because of its conservative nature and high
      concentration factor in commercially valuable species. The brown seaweed
      Ascophyllum nodosum (Linnaeus) Le Jolis was used to biomonitor the spatial
      distribution of (99)Tc around the Welsh coast, an area relatively unstudied with
      respect to this isotope. Over the course of a year an inverse relationship was
      observed between the (99)Tc concentration in A. nodosum samples and approximate
      straight-line distance from Sellafield. These data show that detectable levels of
      a Sellafield derived radionuclide are reaching the Welsh coast despite the
      overall northward movement of the Sellafield plume.

PMID- 16808961
TI  - Cystic endometriosis of the epididymis.
AB  - Endometriosis of the male genitourinary tract is an exceedingly rare entity, with
      only 6 cases reported to date involving the bladder, prostate, lower abdominal
      wall, and paratesticular region. We present what we believe to be the first case
      of cystic endometriosis of the epididymis in a 27-year-old man with scrotal pain,
      describe its pathologic and immunohistochemical features, and discuss its
      pathogenesis.

PMID- 16808962
TI  - Ureteral obstruction after dextranomer/hyaluronic acid copolymer injection for
      treatment of secondary vesicoureteral reflux after renal transplantation.
AB  - Ureteral obstruction after transurethral injection therapy for primary
      vesicoureteral reflux is known to occur in less than 1% of cases. We report the
      first case of a ureteral obstruction after transurethral injection of
      dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of secondary
      vesicoureteral reflux after renal transplantation. Loss of transplant function
      made reimplantation of the ureter necessary. A periureteral phlebitis and
      moderate foreign body reaction was found histologically, although the patient had
      received immunosuppressive therapy. Endoscopic therapy of secondary
      vesicoureteral reflux in patients after renal transplantation is a reasonable
      minimally invasive treatment option; however, severe complications may occur.

PMID- 16808963
TI  - Arteriovenous malformation of scrotum causing virtual azoospermia.
AB  - We report a case of surgical correction of a scrotal arteriovenous malformation
      (AVM) that reversed severe oligospermia. A 31-year-old man was found to have
      virtual azoospermia and left scrotal swelling. The left scrotal mass was
      diagnosed as a varicocele, but the mass did not resolve after bilateral
      microsurgical varicocelectomies. Postoperative pelvic arteriography revealed a
      scrotal AVM that was subsequently embolized. With a microsurgical approach, the
      mass was excised. Surgical correction of the scrotal AVM resulted in marked
      improvement in his semen parameters. The effect of the AVM on spermatogenesis was
      most likely mediated by an elevation in scrotal temperature.

PMID- 16808964
TI  - Metastatic adenocarcinoma of prostate in a healing sternotomy site.
AB  - Metastatic prostate cancer has a strong predilection for osseous sites, where the
      disease spreads in 80% of advanced cases. The molecular mechanisms involved in
      prostate cancer establishment in bone are largely unknown; however, local tissue
      factors, including those involved in wound healing, have been suggested to play a
      critical role. We present a case of tumor explosion in a median sternotomy wound
      after local prostate cancer therapy. This case highlights that novel therapeutic
      interventions that disrupt the apparent synergistic relationship between tumor
      cells and the pro-tumorigenic microenvironment may hold great promise in
      constraining the proliferation of prostate cancer metastases.

PMID- 16808965
TI  - Abdominal electrical stimulation rescues failures to penile vibratory stimulation
      in men with spinal cord injury: a report of two cases.
AB  - Most men with spinal cord injury are anejaculatory. To retrieve their semen for
      insemination, the procedure of penile vibratory stimulation is recommended over
      electroejaculation. Some men with spinal cord injury, however, cannot ejaculate
      with penile vibratory stimulation. We present 2 cases in which a simple, over-the
      counter abdominal muscle stimulator rescued failures to penile vibratory
      stimulation. Use of this safe, easy, and inexpensive method may prevent some
      patients from undergoing more expensive, more invasive sperm retrieval methods
      such as electroejaculation or surgical sperm retrieval from the testis or
      epididymis.

PMID- 16808966
TI  - Feasibility of extraperitoneal laparoscopic para-aortic and common iliac
      lymphadenectomy.
AB  - OBJECTIVE: The aim of this study is to evaluate the feasibility of
      extraperitoneal laparoscopic para-aortic and common iliac lymphadenectomy for
      cervical and endometrial carcinoma. METHODS: Seventy-six patients underwent
      extraperitoneal laparoscopic para-aortic and common iliac lymphadenectomy between
      February 1999 and September 2005. The lymph nodes dissected with the laparoscopic
      procedure included the inframesenteric para-aortic lymph nodes, the sacral lymph
      nodes, and the bilateral common iliac lymph nodes. The extraperitoneal
      laparoscopic operation was performed with pelvic open surgery using Lap Disc to
      ensure the safety of patients. RESULTS: The number of patients with cervical and
      endometrial carcinoma was 36 and 40, respectively. The median age of patients was
      51 years (range 24-75 years). Conversion to open surgery was necessary in 8
      patients. These include 3 patients who encountered blood loss of 400, 136 and 128
      ml; 2 extremely obese women; and 3 patients who had peritoneal tears causing CO2
      gas leakage. Among the remaining 68 patients, the median operating time for
      extraperitoneal laparoscopic para-aortic and common iliac lymphadenectomy was 75
      min (range 45-145 min), and the median estimated blood loss was 5 ml (range 5-138
      ml). The median total number of resected nodes was 14 (range 2-31), and 4
      patients had lymph node metastasis. No patient encountered postoperative
      complications attributable to extraperitoneal laparoscopic para-aortic and common
      iliac lymphadenectomy. CONCLUSIONS: Extraperitoneal laparoscopic para-aortic and
      common iliac lymphadenectomy with pelvic open surgery using Lap Disc is a
      feasible procedure, particularly in the surgeons learning phase.

PMID- 16808967
TI  - Lack of behavioral and neuropathological effects of dietary beta-methylamino-L
      alanine (BMAA) in mice.
AB  - Beta-methylamino-L-alanine (BMAA) is an excitotoxin allegedly involved in ALS
      parkinsonism-dementia complex (ALS-PDC), a neurological disorder found in Guam
      and its surrounding islands, in which motor neuron disease symptoms can present
      alone or can co-occur with parkinsonism and dementia. Although in vitro
      experiments have shown BMAA's neurotoxic properties, studies using adult animals
      and systemic administration which better model the case of environmentally
      induced human neurodegenerative diseases have not supported the involvement of
      BMAA in these disorders. In order to better test the hypothesized role of BMAA in
      neurodegeneration, we fed adult mice BMAA at a dose (28 mg/kg body weight, daily
      for 30 days) that reproduces the natural levels and tested the animals with a
      battery of behavioural tests, the latter including the evaluation of motor
      coordination, motor neuron-mediated reflexes, locomotion, muscular strength and
      memory. We also assessed whether BMAA exposure triggers cell death in the central
      nervous system (CNS) of mice by examining neuronal numbers and glial response in
      the spinal cord and the brain. No motor, cognitive or neuropathological outcome
      resulted from this feeding paradigm. Our findings support neither the causal role
      of BMAA in neurodegeneration nor the specific involvement of this amino acid in
      ALS-PDC.

PMID- 16808968
TI  - Prevalence of leisure-time physical activity in Taiwanese adults: results of four
      national surveys, 2000-2004.
AB  - OBJECTIVES: Literature on the prevalence of physical activity in Asian countries
      is limited, despite evidence of increasing rates of sedentary-related disease
      such as obesity and diabetes. It is important to establish nationally
      representative data in countries such as Taiwan to set up levels and patterns of
      activity and to inform health policy. METHODS: Unpublished data from four cross
      sectional nationally representative surveys comprising 29,226 people aged 20 and
      older were analyzed. We explored the population prevalence of meeting national
      recommendations for health, examined temporal change across a 4-year period, and
      attempted comparisons with neighboring Asian and selected westernized countries.
      Logistic regression analysis provided adjusted odds ratios of physical activity
      engagement for several demographic variables. RESULTS: Around 14% of Taiwanese
      adults met national recommendations. Similar to other Asian countries, but in
      contrast to declines with age seen in western populations, people aged 45 and
      older were more likely to be active than younger people. High-risk groups for
      inactivity were those aged 20-44 with limited formal education and in paid
      employment. CONCLUSIONS: Overall prevalence in leisure-time physical activity was
      low. There is scope to increase active leisure for improving health, particularly
      among younger adults.

PMID- 16808969
TI  - Stages of change for moderate-intensity physical activity in deprived
      neighborhoods.
AB  - BACKGROUND: This article describes the association of external and psychosocial
      factors with the stages of change for moderate-intensity physical activity among
      individuals with generally low socioeconomic positions. METHODS: A self
      administered questionnaire among individuals aged 18-65 years (response rate 60%,
      n = 2781) in deprived neighborhoods in Eindhoven, The Netherlands, was conducted
      in September 2000. To identify factors associated with stages of change an
      ordinal logistic regression model, the "Threshold of Change model (TCM)", was
      used to analyze the data. RESULTS: Thirty-six percent of the respondents were in
      the pre-action stages, 15% was in action and 49% in maintenance. Individuals who
      were, older, lower educated, had low health locus of control, had less knowledge
      of physical activity issues, and presented other risky health behaviors, were
      more likely to be in a lower stage of change category. A positive attitude, high
      self-efficacy expectations, perceiving the physical activity level of others as
      high, and much social support were associated with the higher stages of change
      categories. CONCLUSION: The distribution across the stages of change supports the
      need to improve physical activity behavior in these deprived neighborhoods.
      Interventions need to be tailored to the psychosocial, and the external factors
      that are likely to play a role in the behavioral change process.

PMID- 16808970
TI  - Health outcomes in adolescence: associations with family, friends and school
      engagement.
AB  - AIM: To examine the associations between connectedness to family and friends, and
      school engagement, and selected health compromising and health promoting
      behaviours in a sample of New Zealand adolescents. METHODS: A web-based survey
      was designed and administered to a random sample of 652 Year 11 students aged 16
      years from all Dunedin (NZ) high schools between 30th July and 31st October 2001.
      Connectedness to family and friends, and school engagement were assessed,
      together with reports of various health compromising and health promoting
      behaviours. Logistic regression was used to determine the extent to which these
      family, friends and school variables were related to health compromising and
      health promoting behaviours. RESULTS: School engagement was strongly related to
      both low levels of health compromising and high levels of health promoting
      behaviours. Connectedness to family was associated primarily with fewer reports
      of suicidal ideation and increased reports of physical activity. Connectedness to
      friends was associated in the main with increased reports of health compromising
      behaviours. CONCLUSION: This study reinforces the importance of school and family
      as support networks for young people. School may well play an especially
      important role in health promotion among young people. The mechanisms by which
      engagement with school operates need to be explored further.

PMID- 16808971
TI  - Developmental assessment of competence from early childhood to middle
      adolescence.
AB  - This study represents a developmentally informed, empirically validated
      examination of competence across multiple domains (Social, Cognitive, Emotional
      well-being), gender and age (early childhood, middle childhood, early
      adolescence, middle adolescence). Competence indicators were created and the
      structure of these domains was tested using multi-method, multi-informant data
      collected on 191 participants drawn from a prospective study of at-risk children.
      The results indicated that inter-individual differences in Cognitive and Social
      competence were stable across time, whereas inter-individual differences in
      Emotional well-being were stable only between early and middle adolescence. While
      the strength of stability of Cognitive competence was similar across different
      time points, the stability of Social competence declined after middle childhood,
      suggesting more inter-individual variability with regard to change. The findings
      also indicated that both the structure and the stability of competence are
      similar for boys and girls.

PMID- 16808972
TI  - Polymer microarrays: identification of substrates for phagocytosis assays.
AB  - A polymer microarray of 120 polyurethanes was used to identify polymers that
      promoted the adhesion of bone marrow dendritic cells (BMDC). Identified polymers
      were coated onto glass cover slips and shown to be efficient substrates for the
      immobilisation of these primary cells, which underwent efficient phagocytosis
      while still presumably maintaining their immature state.

PMID- 16808973
TI  - The role of titanium surface topography on J774A.1 macrophage inflammatory
      cytokines and nitric oxide production.
AB  - A role for monocyte/macrophage modulation of wound healing at endosseous implants
      is proposed. The modification of the endosseous implant surface topography can
      alter cell adhesion and resultant cell behavior. The aim of this study was to
      define the effect of increased cpTitanium surface topography on adherent J744A.1
      macrophage phenotype in culture. The J744A.1 cells were cultured on 20mm diameter
      cpTitanium disks prepared with smooth and grit-blasted/acid rough surface
      topographies for 24-72 h. Following culture in growth media with or without
      lipopolysaccharide (LPS), total RNA was isolated and real-time polymerase chain
      reaction (PCR) was used to measure the steady-state levels of the pro
      inflammatory cytokines interleukin 1-beta (IL-1beta) and interleukin 6 (IL-6) and
      the anti-inflammatory cytokine interleukin-10 (IL-10). Additional evidence of pro
      inflammatory signaling was sought by measurement of cellular nitric oxide (NO)
      production. In the absence of LPS, IL-1beta levels were increased on grit
      blasted/acid rough surfaces during the first 48 h. In contrast, IL-6 levels were
      reduced on the grit-blasted/acid rough surfaces. When cultures were treated with
      LPS, high levels of IL-1beta and IL-6 expression were measured, irrespective of
      surface topography. The responses of J744A.1 cells to surface and superimposed
      LPS stimulation suggest only modest effects of the modeled endosseous implant
      surface on adherent cell pro-inflammatory cytokine expression and NO signaling.

PMID- 16808974
TI  - Effect of tetracycline residues in pig manure slurry on tetracycline-resistant
      bacteria and resistance gene tet(M) in soil microcosms.
AB  - Effects of tetracycline residues from pig manure slurry on the prevalence of
      tetracycline-resistant bacteria and the tetracycline resistance gene, tet(M),
      were studied in soil microcosms. Four types of soil microcosms were established
      for a period of 152 days, supplemented with combinations of pig manure slurry and
      a tetracycline-resistant Enterococcus faecalis, CG110, containing the
      tetracycline resistance gene tet(M) (on the conjugative transposon, Tn916). The
      prevalence of both tetracycline-resistant aerobic bacteria and tetracycline
      resistant enterococci declined rapidly until day 45 where no significant
      differences in the levels of tetracycline-resistant bacteria in any of the four
      types of microcosms could be detected. tet(M) could be detected in microcosms
      supplemented with either pig manure slurry and/or E. faecalis CG110 (tet(M)) for
      the whole period (152 days). tet(M) could be detected longer than tetracycline
      resistant enterococci could be isolated (limit of detection 100 CFU/g soil)
      probably due to viable but not culturable (VBNC) bacteria with tet(M), horizontal
      gene transfer of tet(M) to indigenous soil bacteria or presence of "free" DNA.
      The concentration of chlortetracycline and oxytetracycline were almost stable
      through out the experimental period, but the tetracycline concentrations had no
      effect on prevalence of tetracycline-resistant bacteria. The presented microcosm
      approach simulated natural farmland conditions well and supported results from
      previous field studies.

PMID- 16808975
TI  - Nocardia paucivorans--a cause of disseminated nocardiosis.
AB  - We describe a 53-year-old man without discernable immunocompromise who presented
      with cerebral and cutaneous dissemination of primary pulmonary Nocardia
      paucivorans infection. This report also identifies 32 other patients in our
      health area with clinical isolates of N. paucivorans over the last 20 years,
      extending the reported spectrum of disease caused by this organism. At least 30%
      (10/33) of these patients had disseminated disease indicating a propensity of
      this species to disseminate.

PMID- 16808976
TI  - Method for studying behavioural activity patterns during long-term recordings
      using a force-plate actometer.
AB  - The motor activity (MA) patterns of rodents are commonly detected in the
      laboratory using infrared photo-beams or running wheels. In chronobiological
      studies, the MA rhythm is considered as a behavioural output of the circadian
      pacemaker. This paper describes a method to obtain long-term records of MA in
      rodents, with a 1mm spatial resolution and a 1s temporal resolution. The device
      comprised a square platform laid on top of three force transducers, allowed the
      calculation of the coordinates of the centre of force exerted by a freely moving
      rodent, and continuously monitored its displacements. A specific computer program
      processed the trajectories, providing an exhaustive analysis of motion. To test
      this method, motor behavioural activity was studied in rats exposed to conditions
      that favoured rhythmicity: light-dark cycles of both 24 h (LD) and 22 h (T22),
      and constant darkness (DD). In addition, arrhythmicity patterns were studied
      under constant light (LL) conditions, and in animals with permanent lesions of
      the hypothalamic suprachiasmatic nucleus (SCNx). A single description of the
      general MA distribution at 24 h was obtained using infrared photo-beams. By
      contrast, under LD conditions, a 24-h rhythm with ultradian components was seen
      in the total distance travelled, whereas that detected in the number of slow
      motions showed less ultradian components. In addition, a regional preference in
      the nesting place was detected under both LD and DD conditions. In one SCNx
      animal and another exposed to LL conditions, both showing arrhythmicity in photo
      beam-detected MA, a 24 h rhythm was observed in regional preference; other LL
      animal presented a 24 h rhythm in the number of slow motions. This method has
      capabilities lacking in commonly used techniques. The potential uses of this
      approach, principally in cronobiological studies, are discussed.

PMID- 16808977
TI  - Spatial and force dependency of mechanomyographic signal features.
AB  - The aim was to investigate with a novel technique the spatial inhomogeneity in
      surface mechanomyographic (MMG) response to muscle contraction at varying force
      levels. MMG signals were detected over the dominant tibialis anterior muscle of
      10 volunteers using a 5 x 3 grid of accelerometers. The subjects performed 3 s
      long isometric contractions at forces ranging from 0% to 100% of the maximal
      force (10% increment) in a randomised order. From the two-dimensional MMG
      recordings, maps of absolute and normalized temporal and spectral MMG descriptors
      were obtained. The centroid and entropy of these maps were computed to describe
      the spatial centre of activity and degree of homogeneity, respectively. MMG
      absolute amplitude did not depend on location over the muscle while normalized
      amplitude did and the centroid shifted with increasing force. Amplitude increased
      with force and its entropy decreased. Absolute and normalized spectral variables
      depended on location over the muscle and their centroid shifted with increasing
      force. In addition, the dependency of absolute and normalized spectral variables
      on force was affected by location. These results highlight limitations when using
      single-channel MMG features for the assessment of motor unit control strategies,
      due to a substantial effect of position on the relation between force and MMG
      characteristics.

PMID- 16808978
TI  - Is behavioral inhibition a risk factor for depression?
AB  - BACKGROUND: Several studies have reported an observed relationship between a
      behaviorally inhibited temperament early in life and subsequent clinical anxiety,
      but few have explored the relationship between early inhibition and depression.
      METHODS: In a cross-sectional survey of non-clinical adults we examined the
      relationship between retrospectively reported childhood behavioral inhibition and
      lifetime depression. We then examined the mediating role of social anxiety and
      childhood relational stress factors. RESULTS: Subjects who qualified for a
      lifetime episode of depression also reported significantly more childhood
      inhibition, particularly if they had a juvenile onset depression (i.e., by age
      16). Further analyses revealed that social anxiety mediated the link between
      reported childhood inhibition and later depression, and highlighted the
      additional meditating effect of parental influences. CONCLUSION: Any relationship
      between an early inhibited temperament and later depression, may in fact be
      dependent upon the presence of clinically meaningful social anxiety.

PMID- 16808979
TI  - Antimicrobial activity of Substance P and Neuropeptide Y against laboratory
      strains of bacteria and oral microorganisms.
AB  - Infection and inflammation of mucosal tissue may induce the production of
      neuropeptides, specifically Substance P and Neuropeptide Y. Since these
      neuropeptides are similar to antimicrobial peptides in their amino acid
      composition, amphipathic design, cationic charge, and size, we wanted to
      determine if they had antimicrobial activity against a panel of common bacteria
      and oral microorganisms using the radial diffusion assay. Neuropeptide Y and
      Substance P had antimicrobial activity against E. coli (MIC 20.6+/-5.5 microg/ml
      SEM and 71.5+/-15 SEM microg/ml, respectively), but did not have activity against
      laboratory strains of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella
      pneumoniae, and Serratia marcescens (MIC>500 microg/ml) nor oral strains of
      Streptococcus mutans, Candida albicans, and Actinobacillus actinomycetemcomitans
      (MIC>500 microg/ml). While Substance P and Neuropeptide Y did not have direct
      antimicrobial activity against the microorganisms tested, they still may
      stimulate local epithelial cells to produce other innate immune factors like
      defensins and cathelicidins. However, this remains to be determined.

PMID- 16808980
TI  - Delipidation of a hepadnavirus: Viral inactivation and vaccine development.
AB  - Many viruses including HIV, hepatitis C and hepatitis B, have an outer lipid
      envelope which maintains inserted viral peptides in the "correct" functional
      conformation and orientation. Disruption of the lipid envelope by most solvents
      destroys infectivity and often results in a loss of antigenicity. This
      communication outlines a novel approach to viral inactivation by specific solvent
      delipidation which modifies the whole virion rendering it non-infective, but
      antigenic. Duck hepatitis B virus (DHBV) was delipidated using a diisopropylether
      (DIPE) and butanol mixture and residual infectivity tested by inoculation into
      day-old ducks. Delipidation completely inactivated the DHBV (p < 0.001).
      Delipidated DHBV was then used to vaccinate ducks. Three doses of delipidated
      DHBV induced anti-DHBs antibody production and prevented high dose challenge
      infection in five out of six ducks. In comparison, five of six ducks vaccinated
      with undelipidated DHBV and four of four ducks vaccinated with glutaraldehyde
      inactivated DHBV were unprotected (p < 0.05). Although this solvent system
      completely inactivated DHBV, viral antigens were retained in an appropriate form
      to induce immunity. Delipidation of enveloped viruses with specific organic
      solvents has potential as the basis for development of vaccines.

PMID- 16808981
TI  - Searching for ways out of the autism maze: genetic, epigenetic and environmental
      clues.
AB  - Our understanding of human disorders that affect higher cognitive functions has
      greatly advanced in recent decades, and over 20 genes associated with non
      syndromic mental retardation have been identified during the past 15 years.
      However, proteins encoded by "cognition genes" have such diverse
      neurodevelopmental functions that delineating specific pathogenetic pathways
      still poses a tremendous challenge. In this review, we summarize genetic,
      epigenetic and environmental contributions to neurodevelopmental alterations that
      either cause or confer vulnerability to autism, a disease primarily affecting
      social cognition. Taken together, these results begin to provide a unifying view
      of complex pathogenetic pathways that are likely to lead to autism spectrum
      disorders through altered neurite morphology, synaptogenesis and cell migration.
      This review is part of the INMED/TINS special issue "Nature and nurture in brain
      development and neurological disorders", based on presentations at the annual
      INMED/TINS symposium (http://inmednet.com/).

PMID- 16808982
TI  - Experimental data supporting the expression of the highly conserved GnRH-II in
      the brain and pituitary gland of rats.
AB  - The second GnRH form, originally identified in chickens (cGnRH-II or GnRH-II), is
      the most ubiquitous peptide of the GnRH neuropeptide family, being present from
      jawed fish to human beings. However, the presence of GnRH-II in such an important
      experimental model as the rat is still an object of discussion. Here we present
      chromatographic, immunologic and biologic activity evidence supporting the
      expression of GnRH-II in the rat. Olfactory bulb, hypothalamus, remnant brain and
      anterior pituitary from a pool of 50 female adult rats were extracted and
      subjected to RP-HPLC on a C-18 column. The fractions were collected and evaluated
      by using two different RIA systems, specific for GnRH-I and GnRH-II respectively.
      Under these conditions the GnRH-I standard eluted in fraction 21 (f21) was only
      detected with the GnRH-I RIA system, whereas the GnRH-II standard was only
      detected in the fraction 27 (f27) by using a GnRH-II RIA system. In the olfactory
      bulbs extract, the fractions analyzed by the GnRH-I RIA systems showed a single
      peak in f21, whereas by using the GnRH-II RIA system a single peak at f27 was
      observed. In the hypothalamus GnRH-I was detected in f21 meanwhile GnRH-II could
      not be detected. When the remnant brain and pituitary gland extracts were
      analyzed, both GnRH forms were detected. To the best of our knowledge, this is
      the first report concerning GnRH-II detection in a mammalian pituitary. Serial
      dilutions of f27 and GnRH-II presented similar displacement of radioiodinated
      GnRH-II, demonstrating that both molecules share immunological properties.
      Moreover, after 60 min stimulation, both f27 and GnRH-II had similar LH and FSH
      releasing activity in 12 day-old rat pituitary primary cell cultures. However, we
      failed to characterize the GnRH-II gene in this model. These results provide
      strong evidence for the expression of GnRH-II in the rat brain and pituitary
      gland.

PMID- 16808983
TI  - Clozapine induced myocarditis: a rare but fatal complication.
AB  - The need to consider myocarditis as one cause of flu-like symptoms in patients
      taking clozapine should be well entrenched. Suspicion should be heightened if the
      symptoms develop during the first 6-8 weeks of therapy. The FDA and the drug's
      manufacturer have strengthened warnings to include that a potentially fatal
      myocarditis may occur when taking clozapine. We aim to highlight the side effects
      of clozapine and increase awareness of this condition associated with the usage
      of the drug.

PMID- 16808984
TI  - Hearing disturbances in hypertrophic cardiomyopathy. Is the sensorineural
      disorder neurogenic or myogenic?
AB  - BACKGROUND: In a previous study, we demonstrated that a hidden hearing defect is
      present in about 50% of patients with hypertrophic cardiomyopathy (HCM). Such
      defects were found significantly less frequently in age and clinical stage
      matched patients with dilated cardiomyopathy (DCM), and were practically absent
      in patients with valvular aortic stenosis, and in patients taking beta-receptor
      blockers for different reasons (such as hypertension, ischemic heart disease,
      etc.). The hearing disturbances were first examined by means of brain-stem evoked
      response audiometry (BAEP). This method permitted only a rough differentiation
      between the origins of cochlear (myogenic) and retrocochlear (neurogenic) hearing
      disturbances, and did not allow us to establish their myogenic or neurogenic
      nature with certainty. AIMS: Our present aim was to determine whether the hearing
      disturbances present in HCM and DCM patients are myogenic or neurogenic in
      origin. METHODS: The neurogenic function of the inner ear was examined by BAEP as
      before, and the myogenic function by the distortion product otoacoustic emission
      technique. RESULTS: Myogenic abnormalities were found in 39/69 ears (57%) and
      neurogenic abnormalities in 19/69 (28%) ears among the HCM cases, as compared
      with 14/39 (36%) and 8/39 (21%) ears respectively among the DCM cases (p<0.005).
      Healthy controls displayed the lowest incidence of both types of hearing
      abnormalities. CONCLUSION: Our results lead us to conclude that myogenic lesions
      are more frequent than neurogenic lesions in patients with HCM. Both myogenic and
      neurogenic lesions are more frequent in HCM patients than in DCM patients or
      healthy controls. It may be hypothesized that abnormal sarcomeric proteins
      present in the muscular structures of the inner ear in HCM are possibly
      responsible for the hearing disorders in these patients, and that this is not
      merely a neurological defect.

PMID- 16808985
TI  - Bistable perception -- along the processing chain from ambiguous visual input to
      a stable percept.
AB  - The observation of an ambiguous figure leads to spontaneous perceptual reversals
      while the observed picture stays unchanged. Some ERP studies on ambiguous figures
      report a P300-like component correlated with perceptual reversals supporting a
      top-down explanation, while other studies found early visual ERP components
      supporting a bottom-up explanation. Based on an experimental paradigm that
      permits a high temporal resolution of the endogenous reversal event, we compared
      endogenous Necker-cube reversals with exogenously-induced reversals of
      unambiguous cube variants. For both reversal types, we found a chain of ERP
      components with the following characteristics: (1) An early occipital ERP
      component (130 ms) is restricted to endogenous reversals. (2) All subsequent
      components also appear with exogenously-induced reversals, however 40-90 ms
      earlier than their endogenous counterparts. (3) The latency difference between
      reversal types is also reflected in the timing of manual reactions, which occur
      100-130 ms after P300-like components. The results suggest that the P300-like
      component is the same as found in other ERP studies on ambiguous figures. This
      component does not reflect the reversal per se, but rather its cognitive
      analysis, 300 ms after a change of the representation in early visual areas. The
      presented ERP chains integrate the different ERP results and allow to pinpoint
      the steps where top-down mechanisms begin to exert their influence.

PMID- 16808986
TI  - Genomic insights into positive selection.
AB  - The traditional way of identifying targets of adaptive evolution has been to
      study a few loci that one hypothesizes a priori to have been under selection.
      This approach is complicated because of the confounding effects that population
      demographic history and selection have on patterns of DNA sequence variation. In
      principle, multilocus analyses can facilitate robust inferences of selection at
      individual loci. The deluge of large-scale catalogs of genetic variation has
      stimulated many genome-wide scans for positive selection in several species.
      Here, we review some of the salient observations of these studies, identify
      important challenges ahead, consider the limitations of genome-wide scans for
      selection and discuss the potential significance of a comprehensive understanding
      of genomic patterns of selection for disease-related research.

PMID- 16808987
TI  - The quest for the universals of protein evolution.
AB  - The sequences of proteins change at dramatically different rates. Unraveling the
      association between this variability and cellular and ecological processes will
      enable a better understanding of protein function and evolution. Although weak
      associations of protein evolutionary rates with a plethora of variables have been
      reported, none withstands comparison with the effect of expression levels. A
      recent report by Drummond et al. suggests that the dominant role of expression
      levels in slowing the rate of protein evolution stems from selection for
      translation robustness.

PMID- 16808988
TI  - Characterization of a novel cell penetrating peptide derived from Bag-1 protein.
AB  - A highly cationic peptide (BagP), located within the normally expressed human
      protein Bag-1, was tested for its capacity to act as a cell penetrating peptide.
      BagP was found to translocate and transport high molecular weight cargos in
      several cell types, in varying degrees with a preference for adherent cells. The
      penetration phenomenon was not found to be subject to saturation for the highest
      amount of peptide tested (100 microM), whereas the time needed for maximum
      translocation to be achieved, was cell type-dependent. Finally, BagP
      internalization depends on its charge, cellular metabolism and cell-surface
      heparan sulfate proteoglycans.

PMID- 16808989
TI  - Carnitine supplementation in premature neonates: effect on plasma and red blood
      cell total carnitine concentrations, nutrition parameters and morbidity.
AB  - BACKGROUND & AIMS: Carnitine may be considered conditionally essential in the
      neonatal population. The purpose of this study was to evaluate the effects of
      long-term carnitine supplementation on total carnitine status and morbidity in
      premature neonates. METHODS: In this prospective, randomized, placebo-controlled,
      double-blinded study, premature neonates received carnitine supplementation
      (20mg/kg/day) or placebo. Plasma (nmol/ml) and red blood cell (RBC) (nmol/mg
      hemoglobin) total carnitine concentrations, 24-h nitrogen excretion, intake and
      weight, and respiratory, gastroesophageal, and infectious morbidity were
      assessed. RESULTS: Twenty-nine neonates (13 placebo, 16 carnitine; 27+/-2 weeks
      gestation; 976+/-259g birthweight) were studied for up to 8 weeks. Plasma total
      carnitine concentrations exceeded the reference range in the carnitine group
      (weeks 1-8); however, concentrations did not reach reference range until week 4
      in the placebo group. RBC total carnitine concentrations increased, but remained
      below reference range in both the carnitine (weeks 1-6) and placebo (weeks 1-8)
      groups. Carnitine group neonates regained their birthweight more rapidly than
      placebo group neonates (day of life 11.8+/-6 vs. 16.9+/-6.3, P=0.034). In
      addition, percent periodic breathing calculated from cardiopulmonary trend
      monitor data (weeks 1-8) was lower in the carnitine group (0.4+/-0.9 vs. 1.4+/
      1.9, P=0.014). There was no difference with respect to other markers of
      respiratory, gastroesophageal and infectious morbidity or nitrogen balance.
      CONCLUSIONS: Carnitine supplementation at 20mg/kg/day results in increased plasma
      and RBC total carnitine concentrations, has a positive effect on catch-up growth,
      and may improve periodic breathing in premature neonates.

PMID- 16808990
TI  - Elemental diets: are they "diets" or "drugs"?

PMID- 16808991
TI  - Cold intolerance of the hand measured by the CISS questionnaire in a normative
      study population.
AB  - Cold intolerance has been recognized as one of the most disabling sequelae of
      upper extremity trauma, especially when neurovascular structures are involved. In
      this study, we aimed to describe cold intolerance in a normative study
      population, validate the Cold Intolerance Symptom Severity (CISS) questionnaire
      and define the threshold for abnormal cold intolerance. One hundred and eight
      volunteers participated in our study. In addition to the CISS score, information
      about age, gender and previous surgery or trauma to the upper extremity was
      obtained. There were no volunteers with previous peripheral nerve injury and
      subjects with a history of Raynaud's disease, upper extremity injury or surgery
      were excluded (n=40). The CISS scores of the study population (n=68) averaged
      12.9 (SD 8.2). Age and gender were not correlated with CISS score. The upper 95%
      confidence interval of the CISS scores for healthy subjects is about 30. We
      suggest this value as a threshold for pathological cold intolerance.

PMID- 16808992
TI  - Shoulder joint kinetics and pathology in manual wheelchair users.
AB  - BACKGROUND: Manual wheelchair users rely heavily on their upper limbs for
      independent mobility which likely leads to a high prevalence of shoulder pain and
      injury. The goal of this study was to examine the relationship between shoulder
      forces and moments experienced during wheelchair propulsion and shoulder
      pathology. METHODS: Kinetic and kinematic data was recorded from 33 subjects with
      paraplegia as they propelled their wheelchairs at two speeds (0.9 and 1.8 m/s).
      Shoulder joint forces and moments were calculated using inverse dynamic methods
      and shoulder pathology was evaluated using a physical exam and magnetic resonance
      imaging scan. FINDINGS: Subjects who experienced higher posterior force (Odds
      Ratio (OR)=1.29, P=0.03), lateral force (OR=1.35, P=0.047), or extension moment
      (OR=1.35, P=0.09) during propulsion were more likely to exhibit coracoacromial
      ligament edema. Individuals who displayed larger lateral forces (OR=4.35,
      P=0.045) or abduction moments (OR=1.58, P=0.06) were more likely to have
      coracoacromial ligament thickening. Higher superior forces (OR=1.05, P=0.09) and
      internal rotation moments (OR=1.61 P=0.02) at the shoulder were associated with
      increased signs of shoulder pathology during the physical exam. INTERPRETATION:
      Specific joint forces and moments were related to measures of shoulder pathology.
      This may indicate a need to reduce the overall force required to propel a
      wheelchair in order to preserve upper limb integrity. Potential interventions
      include changes to wheelchair setup, propulsion training, or alternative means of
      mobility.

PMID- 16808993
TI  - Does decentralisation improve human resource management in the health sector? A
      case study from China.
AB  - A major obstacle to the provision of health services is lack of an effective
      workforce. Human resource management (HRM) can improve the effectiveness of the
      workforce, though this is difficult in large bureaucratic organisations.
      Decentralisation is a common reform strategy and this paper sets out to examine
      whether HRM would be improved in decentralised settings. Indicators were
      developed for three areas of HR outcome: (i) appropriate staff numbers, with (ii)
      appropriate skills and experience, providing, (iii) appropriate inputs to
      organisational performance. An attempt was made to link these human resource (HR)
      outcomes to relevant HRM actions in two counties--one richer and one poorer--in
      Fujian Province, China. One general county hospital and 5 township health centres
      were selected for study in each country. A health facility-based survey collected
      information on characteristics of the workforce and staff surveys identified
      changes in the management of human resources and staff inputs to performance
      before and after decentralisation. Whilst some benefits were identified from
      decentralising HRM, the complexity of the decentralisation itself, and other
      external pressures coupled with inadequate capacity building meant that some HRM
      actions were not always aligned with health service objectives. Better planning
      and preparation coupled with strong monitoring would increase the chances of
      decentralisation improving HRM in the health sector.

PMID- 16808994
TI  - The use of IRES-based bicistronic vectors allows the stable expression of
      recombinant G-protein coupled receptors such as NPY5 and histamine 4.
AB  - Stable expression of G protein coupled receptors in cell lines is a crucial tool
      for the characterization of the molecular pharmacology of receptors and the
      screening for new antagonists. However, in some instances, many difficulties have
      been encountered to obtain stable cell lines expressing functional receptors.
      Here, we addressed the question of vector optimization to establish cell lines
      expressing the human neuropeptide Y receptor 5 (NPY5-R) or histamine receptor 4
      (HH4R). We have compared bicistronic vectors containing viral or cellular
      internal ribosome entry sites (IRES), co-expressing the receptor and the
      neomycine resistance gene from a single mRNA, to a bigenic vector containing two
      distinct promoters upstream each different genes. This study is the first one to
      validate the use of three cellular IRESs for long-term transgene expression. Our
      results demonstrate for both NPY5-R and HH4R that the bicistronic vectors with
      EMCV, VEGF, FGF1A or FGF2 IRES provide clones expressing functional receptors
      with yields between 25% and 100%. In contrast, the bigenic vector provided no
      functional clones, related to a low expression of NPY5R mRNA. The cell lines
      expressing active receptor were stable after more than 50 passages. These data
      indicate that IRES-based bicistronic vectors are particularly appropriate to
      establish cell clones expressing active G-coupled protein receptors with a high
      yield. In the case of NPY5, it was a new way to produce such a stable cell line.
      Furthermore, the characteristics-presented herein-of this receptor
      pharmacological property are perfectly in line with those reported in the
      literature.

PMID- 16808995
TI  - Prehospital diagnosis of massive ethylene glycol poisoning and use of an early
      antidote.
AB  - We report the case of a patient suspected of voluntary massive poisoning by
      ethylene glycol. Prehospital diagnosis was established by portable blood analyser
      and an early antidote with 4 MP treatment initiated in out-of-hospital setting.
      Use of portable blood analyser in prehospital care should be considered in case
      of suspected massive poisoning by ethylene glycol.

PMID- 16808996
TI  - Phosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in
      rat trigeminovascular system.
AB  - Activation of the trigeminovascular pain signalling system appears involved in
      migraine pathophysiology. However, the molecular mechanisms are only partially
      known. Stimulation of cAMP and cGMP production as well as inhibition of their
      breakdown induce migraine-like headache. Additionally, migraine may be associated
      with mutations in ion channels. The aim of the present study was to describe the
      expression of phosphodiesterase 3 (PDE3) and 5 (PDE5) and cyclic nucleotide-gated
      ion channels (CNG) in cerebral arteries, meninges, and the trigeminal ganglion.
      mRNA for PDE and CNG was determined in the rat middle cerebral artery, basilar
      artery, trigeminal ganglion, and dura mater using real-time PCR. PDE and CNG
      proteins were identified using Western blot. For comparison, rat aorta and
      mesenteric artery were analysed. PDE3A, PDE3B, and PDE5A mRNA were detected in
      all tissues examined except for PDE3A mRNA in dura mater and the trigeminal
      ganglion. PDE5A and PDE3A protein expression was present in both cerebral and
      peripheral arteries, whereas PDE3B protein was present only in the cerebral
      arteries. The CNGA4 and B1 subunit mRNAs were detected in cerebral arteries and
      CNGA2 also in the mesenteric artery. CNGA2 and A3 proteins were found in cerebral
      arteries and dura and CNGA1, CNGA2 and CNGA3 in the trigeminal ganglion. In
      conclusion, PDE3A, PDE3B, PDE5A, and five CNG subunits were expressed in several
      components of the trigeminovascular system of the rat. This suggests that
      modulation of cAMP and cGMP levels by PDE and activation of CNG may play a role
      in trigeminovascular pain signalling leading to migraine headache.

PMID- 16808997
TI  - Enhancement of non-dominant hand motor function by anodal transcranial direct
      current stimulation.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive powerful method
      to modulate brain activity. It can enhance motor learning and working memory in
      healthy subjects. To investigate the effects of anodal tDCS (1 mA, 20 min) of the
      dominant and non-dominant primary motor cortex (M1) on hand motor performance in
      healthy right-handed volunteers, healthy subjects underwent one session of both
      sham and active anodal stimulation of the non-dominant or dominant primary motor
      cortex. A blinded rater assessed motor function using the Jebsen Taylor Hand
      Function Test. For the non-dominant hand, active tDCS was able to improve motor
      function significantly-there was a significant interaction between time and
      condition of stimulation (p = 0.003). Post hoc tests showed a significant
      enhancement of JTT performance after 1 mA anodal tDCS of M1 (mean improvement of
      9.41%, p = 0.0004), but not after sham tDCS (mean improvement of 1.3%, p = 0.84).
      For the dominant hand, however, neither active nor sham tDCS resulted in a
      significant change in motor performance. Our findings show that anodal tDCS of
      the non-dominant primary motor cortex results in motor function enhancement and
      thus confirm and extend the notion that tDCS can change behavior. We speculate
      that the under-use of the non-dominant hand with its associated consequences in
      cortical plasticity might be one of the reasons to explain motor performance
      enhancement in the non-dominant hand only.

PMID- 16808998
TI  - Differential effects of impaired mitochondrial energy production on the function
      of mu and delta opioid receptors in neuronal SK-N-SH cells.
AB  - Oxidative stress contributes to changes in neurosensory processing, including
      pain, that occur during aging and neurodegeneration. The effects of neuronal
      oxidation on the opioid system are poorly understood. In this in vitro study,
      oxidative stress was induced by 3-nitroproprionic acid (3-NPA) in opioid
      responsive differentiated SK-N-SH cells. Changes in the inhibitory effects of
      opioid receptor agonists on intracellular cAMP were used as a marker of the
      function of mu and delta opioid receptors (MOR and DOR, respectively). Cells were
      treated with morphine and selective MOR and DOR agonists and antagonists to
      characterize the function of each receptor subtype. Cyclic AMP (cAMP) was
      measured by enzyme immunoassay. Levels of reactive oxygen species (ROS) were
      assessed using the 2',7'-dichlorofluorescin diacetate assay. Exposure of cells to
      3-NPA resulted in an increase in ROS. After 3-NPA exposure, there was a
      significant attenuation of the inhibitory effect of morphine and DAMGO but not of
      DPDPE on cAMP. In cells pretreated with CTOP, 3-NPA did not change the inhibitory
      effect on cAMP. These findings demonstrate for the first time that under
      conditions of mitochondrial damage, the function of MOR is significantly
      decreased, while the function of DOR does not change, suggesting that the effect
      of 3-NPA on opioid receptors is subtype-specific.

PMID- 16808999
TI  - Instructive role of a peripheral pattern for the central patterning of the
      trigeminal projection at the brainstem and thalamus revealed by an artificially
      altered whisker pattern.
AB  - The central patterning mechanism of neuronal circuits is an important issue in
      developmental neuroscience. We report here the role of a peripheral whisker
      pattern for the patterning of the trigeminal projection at the brainstem and
      thalamus in the mouse somatosensory system. The whisker pattern was manipulated
      by infecting the embryonic epidermis with adenovirus harboring Shh. The ectopic
      expression of Shh led to the induction of extra whiskers and displacement of
      whiskers, where these whiskers were histologically normal. The altered whisker
      pattern was isomorphically represented in the brainstem (barrelette: subnuclei
      principalis and subnuclei interpolaris), thalamus (barreloid) and cortex (barrel)
      as revealed by cytochrome oxidase staining. The barrelette-like pattern of the
      parvalbumin became discernible by immunostaining at P7 in subnuclei principalis
      and at P4 in subnuclei interpolaris in normal mice. These are the barrelette
      neurons projecting to the thalamus and the local circuit within the barrelette.
      The barrelette-like parvalbumin pattern also exhibits the altered whisker pattern
      induced by the adenovirus harboring Shh. These results highlight the role the
      peripheral whisker pattern for the central patterning of the brainstem, thalamus,
      and cortex in the mouse somatosensory system.

PMID- 16809000
TI  - Differential effects of unilateral olfactory deprivation on noradrenergic and
      cholinergic systems in the main olfactory bulb of the rat.
AB  - The lack of environmental olfactory stimulation produced by sensory deprivation
      causes significant changes in the deprived olfactory bulb. Olfactory transmission
      in the main olfactory bulb (MOB) is strongly modulated by centrifugal systems.
      The present report examines the effects of unilateral deprivation on the
      noradrenergic and cholinergic centrifugal systems innervating the MOB. The
      morphology, distribution, and density of positive axons were studied in the MOBs
      of control and deprived rats, using dopamine-beta-hydroxylase (DBH)
      immunohistochemistry and acetylcholinesterase (AChE) histochemistry in serial
      sections. Catecholamine content was compared among the different groups of MOBs
      (control, contralateral, and ipsilateral to the deprivation) using high
      performance liquid chromatography analysis. Sensory deprivation revealed that the
      noradrenergic system developed adaptive plastic changes after olfactory
      deprivation, including important modifications in its fiber density and
      distribution, while no differences in cholinergic innervation were observed under
      the same conditions. The noradrenergic system underwent an important alteration
      in the glomerular layer, in which some glomeruli showed a dense noradrenergic
      innervation that was not detected in control animals. The DBH-positive glomeruli
      with the highest noradrenergic fiber density were compared with AChE-stained
      sections and it was observed that the strongly noradrenergic-innervated glomeruli
      were always atypical glomeruli (characterized by their strong degree of
      cholinergic innervation). In addition to the morphological findings, our
      biochemical data revealed that olfactory deprivation caused a decrease in the
      content of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the
      ipsilateral MOB in comparison to the contralateral and control MOBs, together
      with an increase in noradrenaline levels in both the ipsilateral and
      contralateral MOBs. Our results show that regulation of the noradrenergic
      centrifugal system in the MOB depends on environmental olfactory stimulation and
      that it is highly reactive to sensory deprivation. By contrast, the cholinergic
      system is fairly stable and does not exhibit clear changes after the loss of
      sensory inputs.

PMID- 16809001
TI  - Secondary hyperalgesia in the monoarthritic rat is mediated by GABAB and NK1
      receptors of spinal dorsal horn neurons: a behavior and c-fos study.
AB  - Secondary hyperalgesia in the monoarthritic rat is accompanied by a decrease in
      nociceptive activation of spinal neurons expressing GABA(B) receptors and by the
      opposite effect in the cells expressing neurokinin 1 (NK1)-receptors. In order to
      ascertain the relative role of each receptor, the effects of intrathecal
      administration of SP-saporin (SP-SAP), baclofen or both were evaluated, using a
      model of secondary hyperalgesia that consists of mechanical stimulation of the
      hindlimb skin close to an inflamed joint. Four days after the induction of
      monoarthritis by intraarticular injection of Complete Freund's Adjuvant (CFA), a
      cannula was implanted at T(13)-L(1) level and 10 microl of saline or SP-SAP (10(
      6) M) were intrathecally (i.t.) injected. Fourteen days after CFA-injection, half
      of the animals from each group received i.t. injections of 10 microl saline and
      the remainder were injected with the same volume of baclofen (1 microg). Ten
      minutes later, the animals were behaviorally evaluated by the von Frey test or
      submitted to noxious mechanical stimulation to analyze c-fos expression. The von
      Frey thresholds increased after the treatments, but more pronouncedly after
      baclofen or SP-SAP plus baclofen. In segments L(2)-L(3), the spinal area that
      receives input from the stimulated skin close to the inflamed joint, the numbers
      of Fos-immunoreactive neurons were reduced after the three treatments both in the
      superficial and deep dorsal horn. In segments T(13)-L(1), the numbers of Fos
      immunoreactive neurons were significantly reduced after treatment with SP-SAP
      plus baclofen in both dorsal horn regions, and in the deep dorsal horn after
      baclofen treatment. We conclude that both GABA(B) and NK1 receptors of spinal
      dorsal horn neurons participate in secondary hyperalgesia in the monoarthritic
      rat, although the decrease in GABA inhibition appears to play a more important
      role than the increase in SP-mediated effects.

PMID- 16809002
TI  - The RNA binding and transport proteins staufen and fragile X mental retardation
      protein are expressed by rat primary afferent neurons and localize to peripheral
      and central axons.
AB  - Neuronal proteins have been traditionally viewed as being derived solely from the
      soma; however, accumulating evidence indicates that dendritic and axonal sites
      are capable of a more autonomous role in terms of new protein synthesis. Such
      extra-somal translation allows for more rapid, on-demand regulation of neuronal
      structure and function than would otherwise be possible. While mechanisms of
      dendritic RNA transport have been elucidated, it remains unclear how RNA is
      trafficked into the axon for this purpose. Primary afferent neurons of the dorsal
      root (DRG) and trigeminal (TG) ganglia have among the longest axons in the
      neuraxis and such axonal protein synthesis would be advantageous, given the
      greater time involved for protein trafficking to occur via axonal transport.
      Therefore, we hypothesized that these primary sensory neurons might express
      proteins involved in RNA transport. Rat DRG and TG neurons expressed staufen
      (stau) 1 and 2 (detected at the mRNA level) and stau2 and fragile x mental
      retardation protein (FMRP; detected at the protein level). Stau2 mRNA was also
      detected in human TG neurons. Stau2 and FMRP protein were localized to the
      sciatic nerve and dorsal roots by immunohistochemistry and to dorsal roots by
      Western blot. Stau2 and FMRP immunoreactivities colocalized with transient
      receptor potential channel type 1 immunoreactivity in sensory axons of the
      sciatic nerve and dorsal root, suggesting that these proteins are being
      transported into the peripheral and central terminals of nociceptive sensory
      axons. Based on these findings, we propose that stau2 and FMRP proteins are
      attractive candidates to subserve RNA transport in sensory neurons, linking somal
      transcriptional events to axonal translation.

PMID- 16809003
TI  - Combined minocycline plus pyruvate treatment enhances effects of each agent to
      inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic
      animal model of Huntington's disease.
AB  - The combination effects of minocycline (MC), a second-generation tetracycline
      compound and pyruvate (PY), a glycolysis end metabolite with antioxidant activity
      were investigated in the rat striatum following an excitotoxic insult. Striatal
      injection of quinolinic acid (QUIN) resulted in marked inflammation characterized
      by microgliosis, astrogliosis and enhanced expressions of pro-inflammatory
      enzymes inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory
      responses were attenuated with administration of either MC or PY, however, the
      combination of both compounds was significantly more effective in reducing
      inflammation relative to MC or PY applied alone. Immunohistochemical analysis at
      7 days post-intrastriatal QUIN injection showed extensive oxidative stress
      evident as lipid peroxidation, oxidative DNA damage and reactive oxygen species
      formation which was partially decreased by each agent applied separately but
      markedly inhibited with the combination of the two compounds. In addition,
      combination treatments significantly reduced neuronal loss in QUIN-injected
      striatum compared with the agents applied separately. Furthermore, long-term
      combination treatment decreased striatal lesions and inflammation after QUIN
      injection. These results demonstrate that MC and PY confer a considerably
      enhanced anti-inflammatory and neuroprotective efficacy when applied together and
      suggest this combinatorial procedure as a novel therapeutic strategy in
      neurodegenerative disorders such as Huntington's disease which exhibit
      excitotoxic insults.

PMID- 16809004
TI  - Expression of human ATM cDNA in Atm-deficient mouse brain mediated by HSV-1
      amplicon vector.
AB  - Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by
      neurodegeneration, immunodeficiency, cancer predisposition, genome instability,
      and radiation sensitivity. Herpes simplex virus type 1 (HSV-1) amplicon vectors
      provide a means to deliver large genes to the nervous system efficiently and
      safely. We have generated an amplicon vector, carrying human FLAG-tagged A-T
      mutated (ATM), as well as an enhanced green fluorescent protein (EGFP) marker
      gene. Due to the lack of effective and reliable antibodies for ATM and FLAG
      appropriate for immunohistochemistry in mouse tissue sections, expression of the
      human FLAG-tagged ATM was confirmed in the mouse cerebellum at the RNA level by
      reverse transcription followed by quantitative PCR, and by radioactive in situ
      hybridization. In addition, we were able to immunoprecipitate the full-length
      human ATM protein from the cerebella of Atm -/- mice post-infection. This vector
      has been injected into the cerebella of Atm -/- mice with gene delivery to
      thousands of cells, including Purkinje cells, based on the EGFP marker gene. The
      expression of human FLAG-tagged ATM has been demonstrated in the cerebella of Atm
      /- mice at the transcription and translational level three days post-infection.
      To our knowledge, this is the first report of vector-mediated delivery of the
      human ATM cDNA to an Atm -/- mouse. These vectors provide the groundwork to
      develop gene therapy approaches for A-T patients.

PMID- 16809005
TI  - The mitogen-activated/extracellular signal-regulated kinase kinase 1/2 inhibitor
      U0126 induces glial fibrillary acidic protein expression and reduces the
      proliferation and migration of C6 glioma cells.
AB  - The extracellular signal-regulated kinase (ERK) signaling pathway has been
      implicated in diverse cellular functions. ERK and its activating kinase, mitogen
      activated/extracellular signal-regulated kinase kinase (MEK), are downstream of
      cell surface receptors known to be up-regulated in many malignant gliomas. We
      sought to investigate the role of ERK in glioma cell migration, proliferation and
      differentiation using the rat-derived C6 glioma cell line and the MEK inhibitor,
      U0126. Treatment of C6 cells with U0126 caused a significant concentration
      dependent reduction in cell proliferation and migration and also induced
      expression of glial fibrillary acidic protein, a marker of astrocytic
      differentiation. These results suggest that the ERK pathway regulates glioma cell
      proliferation, migration and differentiation.

PMID- 16809006
TI  - Genes associated with neuronal differentiation of precursors from human brain.
AB  - Aiming to gain insights into the mechanisms of neuronal differentiation, we
      describe the first differential expression profiles of purified homogenous neural
      precursors (CD133+ cells from human fetal brain) with those of differentiated
      neurons from human fetal brain. The purity of the two populations of cells was
      verified by flow cytometry and immunocytochemistry, and cells were then processed
      for DNA microarray analysis. We confirmed the expression of several previously
      reported genes (e.g. cell cycle-, DNA replication- and apoptosis-related genes).
      In addition, we identified, and confirmed by reverse transcription-polymerase
      chain reaction and in situ hybridization, significant differential expression of
      platelet-derived growth factor receptor-alpha and insulin-like growth factor
      binding protein 4, indicating these factors as potential pro-neuronal
      differentiation factors. In summary, by using the microarray technique to perform
      a comparative analysis of the genes involved in the differentiation of neural
      precursors, enriched from the human fetus, we have identified hitherto unknown
      candidate genes and related signaling pathways that might play an essential role
      in neuronal differentiation.

PMID- 16809007
TI  - Orexin A mediation of time spent moving in rats: neural mechanisms.
AB  - The brain regulates energy balance and spontaneous physical activity, including
      both small- and large-motor activities. Neural mediators of spontaneous physical
      activity are currently undefined, although the amount of time spent in sedentary
      positions versus standing and ambulating may be important in the energetics of
      human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and
      projecting throughout the neuraxis, enhances arousal and spontaneous physical
      activity. To test the hypothesis that orexin A affects the amount of time spent
      moving, we injected orexin A (0-1000 pmol) into three orexin projection sites in
      male Sprague-Dawley rats: hypothalamic paraventricular nucleus, rostral lateral
      hypothalamic area and substantia nigra pars compacta, and measured spontaneous
      physical activity. Orexin A affects local GABA release and we co-injected orexin
      A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is
      important to substantia nigra function and so we also co-injected a dopamine 1
      receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all
      brain sites orexin A significantly increased time spent vertical and ambulating.
      Muscimol significantly and dose-dependently inhibited orexin A effects on time
      spent moving only when administered to the rostral lateral hypothalamic area. In
      the substantia nigra pars compacta, SCH 23390 completely blocked orexin A-induced
      ambulation. These data indicate that orexin A influences time spent moving, in
      three brain sites utilizing separate signaling mechanisms. That orexin A
      modulation of spontaneous physical activity occurs in brain areas with multiple
      roles indicates generalization across brain site, and may reflect a fundamental
      mechanism for enhancing activity levels. This potential for conferring physical
      activity stimulation may be useful for inducing shifts in time spent moving,
      which has important implications for obesity.

PMID- 16809008
TI  - Sexual dimorphism in the organization of the rat hypothalamic infundibular area.
AB  - The hypothalamic infundibular area is located outside the blood-brain barrier and
      includes, the ventromedial arcuate nucleus (vmARC) sensing circulating
      substances, and the median eminence (ME) where neurohormones are released into
      the hypothalamo-hypophysial vasculature. This integrated functional unit, pivotal
      in endocrine control, adjusts neuroendocrine output to feedback information.
      Despite a differing physiology in males and females, this functional unit has not
      appeared differently organized between sexes. Using immunocytochemistry, we
      describe here for the first time in adult rats, a conspicuous sex-difference in
      its axonal wiring by intrinsic glutamatergic neurons containing the neuropeptides
      neurokinin B (NKB) and dynorphin. In the male, NKB neurons send axons to
      capillary vessels of the vmARC and of the ME (only where gonadotropin-releasing
      hormone (GnRH) axons terminate). Electron microscopy revealed that NKB axons
      target the barrier of tanycytes around fenestrated capillary vessels (in addition
      to GnRH axons), suggesting a control of regional bidirectional permeability. In
      the female, NKB neurons send axons to the neuropile of the vmARC, suggesting a
      direct control of its sensor neurons. The other projections of NKB neurons,
      studied by surgical isolation of the ARC-ME complex and confocal microscopy, are
      not sexually dimorphic and target both integrative and neuroendocrine centers
      controlling reproduction and metabolism, suggesting a broad influence over
      endocrine function. These observations demonstrate that the mechanisms subserving
      hypothalamic permeability and sensitivity to feedback information are sexually
      dimorphic, making the infundibular area a privileged site of generation of the
      male-to-female differences in the adult pattern of pulsatile hormonal secretions.

PMID- 16809009
TI  - Endo-abdominal hypertension complicating pregnancy & fetal development.

PMID- 16809010
TI  - Combination strategies for enhancing transdermal absorption of sumatriptan
      through skin.
AB  - The aim of the present work was to characterize in vitro sumatriptan transdermal
      absorption through human skin and to investigate the effect of chemical enhancers
      and iontophoresis applied both individually and in combination. A secondary
      objective was to compare the results obtained with those in porcine skin under
      the same conditions, in order to characterize the relationship between the two
      skin models and validate the porcine model for further research use. Transdermal
      flux of sumatriptan was determined in different situations: (a) after pre
      treatment of human skin with ethanol, Azone (1-dodecyl-azacycloheptan-2-one),
      polyethylene glycol 600 and R-(+)-limonene, (b) under iontophoresis application
      (0.25 and 0.50 mA/cm(2)) and (c) combining chemical pre-treatment and
      iontophoresis at 0.50 mA/cm(2) current density. All the strategies applied
      enhance sumatriptan transdermal absorption. A linear relationship between the
      fluxes in the two skin models in the different conditions assayed can be
      established. The combination of both strategies, Azone and iontophoresis, proved
      to be the most effective of the techniques for enhancing the transdermal
      absorption of sumatriptan. The flux obtained with porcine skin in vitro is
      approximately double that obtained in human skin.

PMID- 16809011
TI  - Antioxidant activity of caffeoyl quinic acid derivatives from the roots of
      Dipsacus asper Wall.
AB  - The methanol extract from Dipsacus asper Wall (Dipsacaceae) was found to show
      antioxidant activity against free radical and Cu(2+)-mediated LDL oxidation. In
      further study, to identify active constituents from the plant, six caffeoyl
      quinic acid derivatives: 3,4-di-O-caffeoylquinic acid (1), methyl 3,4-di-O
      caffeoyl quinate (2), 3,5-di-O-caffeoylquinic acid (3), methyl 3,5-di-O-caffeoyl
      quinate (4), 4,5-di-O-caffeoylquinic acid (5) and methyl 4,5-di-O-caffeoyl
      quinate (6) were isolated. Their structures were identified by spectroscopic
      methods including 2D-NMR. The isolated compounds, 1-6, were found to be potent
      scavengers of the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), and are more
      potent than butylated hydroxyl toluene (BHT) used as a positive control. The
      compounds 1-6 also inhibited Cu(2+)-mediated low-density lipoprotein (LDL)
      oxidation. They increased the lag time of conjugated dienes formation and
      inhibited the generation of thiobarbituric acid reactive substances (TBARS) in a
      dose-dependent manner. These results suggested that Dipsacus asper due to its
      antioxidant constituents, 1-6, may have a role to play in preventing the
      development and progression of atherosclerotic disease.

PMID- 16809012
TI  - Extraction and analysis of clonazepam and 7-aminoclonazepam in whole blood using
      a dual internal standard methodology.
AB  - In this paper, a simple and robust method for the determination of clonazepam and
      its primary metabolite (7-aminoclonazepam) in whole blood is described.
      Clonazepam (klonopin) is a popular prescription drug that has been implicated in
      the field of drug facilitated sexual assaults (DFSA). Clonazepam, 7
      aminoclonazepam and the internal standards (deuterated analogues for GC-MS
      analysis and nitrazepam for analysis by LC-PDA/GC-MS) were spiked into blood
      samples. The samples were buffered with a pH 6-phosphate solution (5 mL) and
      extracted from phenyl spe columns. The columns were washed with 5% acetonitrile
      in pH 6-phosphate buffer (3 mL) and eluted with ethyl acetate (2 x 3 mL). The
      eluents were evaporated for further chromatographic analysis. For GC-MS, the
      samples were derivatized prior to analysis. When performed with LC-PDA the
      samples were reconstituted in distilled water. From this method LOQs of 5 ng/mL
      of sample is easily achievable by either chromatographic system. By using GC-MS
      in EI mode, 1 ng/mL of sample can be detected. Data is presented here to show the
      simplicity and efficiency of the extraction scheme. By employing the properties
      of GC-MS and LC-PDA, this extraction and analysis procedure further extends the
      number of tools open to the forensic toxicologist for the analysis of this drug.

PMID- 16809013
TI  - [Three cases of cutaneous blastomycosis].
AB  - Blastomycosis is a rare mycotic infection in Africa. Isolated cutaneous disease
      is extremely rare. We report three cases of cutaneous blastomycosis confirmed by
      istologic and mycologic examination. No visceral involvement was found.
      Blastomycosis is rare in Tunisia. The most common site of involvement is the
      lung. The three cases reported presented with skin involvement only, suggesting a
      cutaneous inoculation of Blastomyces dermatitidis. The diagnostic criteria of
      cutaneous blastomycosis are discussed.

PMID- 16809014
TI  - Deletion of the life span determinant p66Shc prevents age-dependent increases in
      emotionality and pain sensitivity in mice.
AB  - Oxidative stress has been implicated in the aging process. Previous studies have
      determined that mice with a targeted mutation of the p66(Shc) gene show reduced
      oxidative stress and extended life span. This study is the first behavioral
      characterization of mice carrying a deletion of p66(Shc). Four-, 11- and 24
      months-old homozygous knockout and wild-type mice of the 129Sv/Ev strain
      underwent a battery of behavioral tests. Locomotion and exploratory activity were
      tested in the open-field test, emotional reactivity was assessed in the elevated
      plus-maze, while nociception was evaluated by means of the hot-plate test (50
      degrees C). In addition, social behavior was assessed in a social interaction
      test. Our results indicate that pain sensitivity and emotional behavior in wild
      type mice increase with age. Deletion of the p66 gene results in an increase in
      pain threshold and reduced emotionality, differences with wild-type subjects
      becoming more pronounced with age. Thus reduced oxidative stress throughout the
      life span is able to prevent some behavioral effects of aging, particularly in
      response to painful or emotionally arousing stimuli. These data are discussed in
      relation to recent views, indicating new and complex interactions between
      oxidative stress and emotional stress.

PMID- 16809015
TI  - Age-related effect of peptide YY (PYY) on paw edema in the rat: the function of
      Y1 receptors on inflammatory cells.
AB  - It is well documented that neuropeptides participate in local inflammatory
      reaction and modulate functions of inflammatory cells. The aim of the study was
      to determine a link between in vivo and in vitro effects of NPY-related peptides
      on inflammatory response with respect to ageing. Peptide YY (PYY) intraplantarly
      applied decreases concanavalin A-induced paw edema in 3 and 8 months, but not in
      24 months old male rats of Albino Oxford strain. The use of NPY-related receptor
      specific peptides and Y1 receptor antagonist revealed that anti-inflammatory
      effect of PYY is mediated via NPY Y1 receptors. PYY in vitro decreases adherence
      of macrophages from 8 months, but not from 3 and 24 months old rats and this
      effect is also mediated via NPY Y1 receptor. Additionally, PYY (10(-6)M)
      decreases NBT reduction in macrophages from 3 and 8 months old rats, and
      suppresses NO production in cells from 24 months old rats, albeit regardless of
      absence of in vivo effect of PYY on inflammation in aged rats. It is concluded
      that aged rats are less responsive to anti-inflammatory action of PYY compared to
      adult and young rats, and that ageing is associated with altered NPY Y1 receptor
      functioning.

PMID- 16809016
TI  - [Patient satisfaction after anaesthesia: which are the relevant parameters?].

PMID- 16809017
TI  - Cadmium-induced apoptosis in rat hepatocytes does not necessarily involve caspase
      dependent pathways.
AB  - Cadmium (Cd) is a well-known hepatotoxic environmental pollutant. Depending on
      the exposure conditions, Cd may cause necrosis or apoptosis. Oxidative stress is
      believed to participate in Cd toxicity but the molecular signaling responsible
      for Cd-induced apoptosis in non-malignant liver cells still needs to be
      clarified. Therefore we have studied apoptosis in primary cultures of rat
      hepatocytes incubated with low levels of Cd for short exposure times. Studies of
      nuclear morphology, chromatin condensation, and oligonucleosomal DNA
      fragmentation demonstrate that 1-5 microM Cd induces apoptosis as early as 6-12 h
      with minor effects on MTT activity. A concomitant time- and concentration
      dependent increase in caspase-9 and -3 activities was observed, whereas Cd did
      not affect caspase-8 activity as much, suggesting a minor role of the death
      receptor pathway. Significant release of cytochrome c into the cytosol
      demonstrated the involvement of a mitochondrial-dependent apoptotic pathway.
      However, cell pre-treatment with caspase inhibitors (Z-VAD-fmk or Ac-DEVD-CHO)
      did not prevent apoptosis. Increases in the cytosolic levels of the mitochondrial
      apoptosis-inducing factor (AIF) were also observed: kinetics of cytochrome c and
      AIF release were similar. These results show that Cd-induced apoptosis in rat
      hepatocytes is time- and concentration-dependent. The early apoptotic events
      involved mitochondrial-dependent pathways but not necessarily caspase-dependent
      signaling.

PMID- 16809018
TI  - Dissociation in children's trauma narratives: an exploratory investigation.
AB  - This research examined the nature of children's trauma narrative themes and the
      relationship between these themes and concurrent and future trauma symptoms.
      Eighty-seven children aged 7-15 years, and their parents, participated following
      child exposure to a traumatic event requiring hospitalization. At 4-7 weeks post
      trauma, a diagnostic interview was conducted with parents and a trauma narrative
      was obtained from the child. At 6 months post-trauma the diagnostic interview was
      re-conducted. Results provided only weak evidence of an association between
      dissociative trauma narrative themes and PTSD symptoms. Specifically, children
      who showed temporal disorganization, but not absence of emotion or dissociative
      amnesia, in narrative themes were more likely to report concurrent subsyndromal
      PTSD symptoms at 4-7 weeks post-trauma. Children who showed absence of emotion
      (or at least one dissociative theme) in the trauma narrative were more likely to
      show symptoms of hyperarousal, but not other symptoms of PTSD, at 6 months post
      trauma. These findings have implications for understanding the role of
      dissociation and the development of PTSD in children.

PMID- 16809019
TI  - PCBs and cognitive functioning of Mohawk adolescents.
AB  - This paper reports on the relationships between the cognitive functioning and PCB
      current body burdens of adolescents in the Mohawk Nation of Akwesasne where there
      is concern about industrial pollution of the environment. Three cognitive tests
      (Woodcock Johnson-Revised, Test of Memory and Learning, and Ravens Progressive
      Matrices) provide 13 subtests that allow a variety of cognitive outcomes to be
      assessed. A summary measure of PCB level was created from the congeners detected
      in at least 50% of the participants. The most notable finding was the significant
      negative relationship between PCB levels and two separate measures of long term
      memory. There was also a negative relationship with a measure of comprehension
      and knowledge. Significant relationships were not large, but provide evidence of
      subtle negative effects of PCB exposure.

PMID- 16809020
TI  - Adaptive filtering with the self-organizing map: a performance comparison.
AB  - In this paper we provide an in-depth evaluation of the SOM as a feasible tool for
      nonlinear adaptive filtering. A comprehensive survey of existing SOM-based and
      related architectures for learning input-output mappings is carried out and the
      application of these architectures to nonlinear adaptive filtering is formulated.
      Then, we introduce two simple procedures for building RBF-based nonlinear filters
      using the Vector-Quantized Temporal Associative Memory (VQTAM), a recently
      proposed method for learning dynamical input-output mappings using the SOM. The
      aforementioned SOM-based adaptive filters are compared with standard FIR/LMS and
      FIR/LMS-Newton linear transversal filters, as well as with powerful MLP-based
      filters in nonlinear channel equalization and inverse modeling tasks. The
      obtained results in both tasks indicate that SOM-based filters can consistently
      outperform powerful MLP-based ones.

PMID- 16809021
TI  - Interactions between GABA-B1 receptors and Kir 3 inwardly rectifying potassium
      channels.
AB  - gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in
      the mammalian brain. It acts via both ionotropic GABA-A and metabotropic GABA-B
      receptors. We evaluated the interaction of receptors with members of the inwardly
      rectifying potassium (Kir 3) channel family, which also play an important role in
      neuronal transmission and membrane excitability. These channels are functionally
      regulated by GABA-B receptors. Possible physical interactions between GABA-B
      receptor and Kir 3 channels expressed in HEK cells were evaluated using
      Bioluminescence Resonance Energy Transfer (BRET) experiments, co
      immunoprecipitation and confocal microscopy. Our data indicate that Kir 3
      channels and Gbetagamma subunits can interact with the GABA-B(1) subunits
      independently of the GABA-B(2) subunit or Kir 3.4 which are ultimately
      responsible for their targetting to the cell surface. Thus signalling complexes
      containing GABA-B receptors, G proteins and Kir channels are formed shortly after
      biosynthesis most likely in the endoplasmic reticulum.

PMID- 16809022
TI  - CpG DNA enhances macrophage cell spreading by promoting the Src-family kinase
      mediated phosphorylation of paxillin.
AB  - Macrophages are an important component of the innate immune response to infection
      by microbial pathogens. The activation of macrophages by pathogens is largely
      mediated by Toll-like receptors (TLRs). Bacterial DNA, which contains
      unmethylated CpG dinucleotide motifs, is specifically recognised by TLR9 and
      triggers the activation of a complex network of intracellular signalling pathways
      that orchestrates the ensuing inflammatory responses of macrophages to the
      pathogen. Here, we have established that CpG DNA promotes reorganisation of the
      actin cytoskeleton and enhances cell spreading by primary mouse bone marrow
      macrophages. CpG DNA stimulation resulted in an approximately 70% increase in
      cell size. Notably, CpG DNA-induced cell spreading was dependent on the activity
      of Src-family kinases. Tyrosine phosphorylation of several proteins was increased
      in a Src-family kinase-dependent manner following CpG DNA stimulation of bone
      marrow macrophages, including the cytoskeletal protein paxillin. Paxillin was
      phosphorylated both in vitro and in vivo by the Src-family kinase Hck.
      Significantly, paxillin from CpG DNA-stimulated bone marrow macrophages had a
      greater capacity to bind the SH2 domain of the adapter protein Crk than did
      paxillin from unstimulated bone marrow macrophages. Furthermore, phosphorylation
      of paxillin by Hck created a binding site for Crk. We propose that the formation
      of paxillin-Crk complexes may mediate the cytoskeletal changes that underlie the
      increased cell spreading of macrophages following their activation by CpG DNA.

PMID- 16809023
TI  - Improvement of leukocyte functions in prematurely aging mice after five weeks of
      diet supplementation with polyphenol-rich cereals.
AB  - OBJECTIVE: We investigated the beneficial effects of diet supplementation with
      two types of cereals naturally rich in polyphenolic compounds on several
      functions of peritoneal leukocytes from prematurely aging mice (PAM). METHODS:
      Two-hundred sixty healthy mice, 8 wk of age, were recruited and their behavioral
      responses were tested in a simple T-maze to identify PAM. Then the mice were fed
      a diet supplemented with 20% (wt/wt) of two different cereal fractions, named B
      (wheat germ) and C (buckwheat flour), rich in polyphenols (gallic acid, catechin,
      p-hydroxybenzoic acid, vanillic acid, p-coumaric acid, sinapic acid, ferulic
      acid, quercetin, and rutin), or a standard diet (controls) for 5 wk. Several
      parameters of innate (adherence to tissues, chemotaxis, phagocytosis,
      microbicidal capacity, and natural killer activity) and acquired immune
      (lymphoproliferation and interleukin-2 release) responses were measured. RESULTS:
      The PAM control group showed worse immune functions (P < 0.001 to 0.05) compared
      with the non-PAM control group. The PAM group that received cereal B showed
      increases in phagocytosis (P < 0.01), microbicidal activity (P < 0.001 to 0.01),
      natural killer activity (P < 0.001) and lymphoproliferation in response to
      lipopolysaccharide (P < 0.01) and interleukin-2 release (P < 0.001), and the PAM
      group that received cereal C showed a similar pattern, with increases in
      macrophage chemotaxis (P < 0.01), phagocytosis (P < 0.01), microbicidal activity
      (P < 0.001 to 0.01), natural killer activity (P < 0.01), lymphoproliferative
      response to concanavalin A and lipopolysaccharide (P < 0.001), and interleukin-2
      release (P < 0.001). CONCLUSIONS: Dietary supplementation with polyphenol-rich
      cereals appears to have a protective effect on immune cell functions in mice with
      premature senescence. Thus, regular intake of these compounds could delay normal
      aging and improve quality of life.

PMID- 16809024
TI  - Remediation of emotion perception deficits in schizophrenia: the use of
      attentional prompts.

PMID- 16809025
TI  - Identification and transcriptional organization of aerobactin transport and
      biosynthesis cluster genes of Vibrio hollisae.
AB  - We had previously reported that Vibrio hollisae produces aerobactin in response
      to iron starvation. In the present study, we identified in V. hollisae ATCC33564
      the aerobactin system cluster which consists of eight genes, hatCDB, iucABCD and
      iutA. The hatCDB genes encode proteins homologous to components of bacterial ATP
      binding cassette transport systems for ferric aerobactin. The iucABCD and iutA
      orthologs code for aerobactin biosynthesis enzymes and the ferric aerobactin
      receptor, respectively. In accordance with their iron-regulated expression,
      putative Fur box sequences were found within the respective promoter regions of
      hatC, iucA and iutA. The monocistronic iutA transcript was detected by northern
      blotting. Moreover, phenotypic comparison between the wild-type strain and its
      targeted gene disruptants supported the biological functions that were expected
      for the respective operons and genes on the basis of the homology search. The
      arrangement of the aerobactin gene clusters thus far found in Vibrio and
      enterobacterial species was compared and discussed from an evolutionary point of
      view.

PMID- 16809026
TI  - [Consumption of carbohydrates by children and adolescents].

PMID- 16809027
TI  - Corynebacterium glutamicum superoxide dismutase is a manganese-strict non
      cambialistic enzyme in vitro.
AB  - Superoxide dismutase (SOD) of Corynebacterium glutamicum was purified and
      characterized. The enzyme had a native molecular weight of about 80kDa, whereas a
      monomer with molecular weight of 24kDa was found on SDS-PAGE suggesting it to be
      homotetramer. The native SOD activity stained gel revealed a unique cytosolic
      enzyme. Supplementing growth media with manganese increased the specific activity
      significantly, while adding iron did not result in significant difference. No
      growth perturbation was observed with the supplemented media. In vitro metal
      removal and replacement studies revealed conservation of about 85% of the
      specific activity by substitution with manganese, while substitution with copper,
      iron, nickel or zinc did not restore any significant specific activity. Manganese
      was identified by atomic absorption spectrometer, while no signals corresponding
      to fixing other metallic elements were detected. Thus, C. glutamicum SOD could be
      considered a strict (non-cambialistic) manganese superoxide dismutase (MnSOD).

PMID- 16809028
TI  - RAPD cluster analysis and chlorate sensitivity of some Indian isolates of
      Macrophomina phaseolina from sorghum and their relationships with pathogenicity.
AB  - Charcoal rot caused by Macrophomina phaseolina is an economically important
      disease in sorghum grown during the post rainy season in India. Variations in
      random amplified polymorphic DNA (RAPD) polymorphisms, chlorate sensitivity and
      pathogenicity were studied among sorghum isolates of M. phaseolina collected from
      different parts of India. RAPD data based on 14 random primers of Kit A and C
      (OPA and OPC) on 20 isolates showed a high degree of polymorphism (98.1%) in
      different isolates. UPGMA dendrogram on RAPD data produced 7 clusters at the
      level of 37% similarity. Isolates from the same locations showed a tendency to
      group closer, substantiating closer genetic relatedness. Sorghum infecting
      Macrophomina isolates showed a mixed response for sensitivity to potassium
      chlorate (120 mM). Chlorate-resistant isolates were predominant (>65% of the
      isolates) over sensitive isolates. Chlorate-sensitive isolates were found to be
      genetically closer among them than the resistant ones. For the first time it was
      shown that chlorate sensitivity in Macrophomina had some relations with charcoal
      rot severity in sorghum.

PMID- 16809029
TI  - Sensitivity enhancement of DNA microarray on nano-scale controlled surface by
      using a streptavidin-fluorophore conjugate.
AB  - High throughput analysis of DNA in low concentration and small volume is an
      important issue and a continuing challenge in the field of DNA microarray and
      sensor. Recently, we have demonstrated that the DNA microarray on nano-scale
      controlled surface provides ample space for hybridization resulting in the best
      discrimination efficiency for SNP analysis. Here, we report the utility of the
      nano-scale controlled surface in conjunction with a multiply tagged protein.
      Application of streptavidin-fluorophore conjugates in combination with the highly
      controlled surface that suppresses non-specific binding of DNA allows highly
      sensitive detection of DNA while maintaining superior SNP discrimination
      efficiency comparable to our earlier results. The sensitivity of DNA microarray
      on the mesospaced surface is two orders of magnitude higher than that of the
      generic surface when a streptavidin-fluorophore conjugate was employed, and the
      detection limit on the former surface was found to be 50 fM of 15-mer target DNA.
      Various streptavidin-fluorophore conjugates including streptavidin-Cy3,
      streptavidin-Cy5, streptavidin-Alexa Flour 555 and streptavidin-phycoerythrin
      were examined.

PMID- 16809030
TI  - Tissue inhibitor of metalloproteinases-1 in the postoperative monitoring of
      colorectal cancer.
AB  - The aim of this study was to investigate whether the pre- and postoperative
      plasma levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) were
      associated with outcome in colorectal cancer (CRC). Pre- and postoperative plasma
      TIMP-1 from 280 curatively resected CRC patients and carcinoembryonic antigen
      (CEA) in corresponding serum samples were measured and correlated with patient
      outcome (death, local recurrence (LR) and distant metastases (DM)). The results
      showed that the course of plasma TIMP-1 from pre- to postoperative levels
      correlated with patient outcome (P=0.005). However, postoperative plasma TIMP-1
      alone was strongly associated with patient outcome, high TIMP-1 predicting short
      survival (P=0.002). Combining postoperative TIMP-1 and CEA demonstrated that high
      TIMP-1 and CEA levels predicted poor outcome (P<0.0001); multivariate analysis
      identifying both parameters as strong prognostic factors for survival, LR and DM
      (P<0.0001). In conclusion, postoperative plasma TIMP-1 predicts patient outcome
      both alone and in combination with CEA. Postoperative TIMP-1 may be a marker of
      residual disease after primary surgery for CRC.

PMID- 16809031
TI  - Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of
      colorectal carcinogenesis.
AB  - Colorectal carcinogenesis is initiated mainly by aberrant activation of the Wnt
      signaling pathway, caused by mutation of either APC or beta-catenin (CTNNB1)
      gene. Poly(ADP-ribose) polymerase-1 (PARP-1) is a highly conserved nuclear
      enzyme, which binds tightly to DNA and plays a role in DNA repair, recombination,
      proliferation and genomic stability. It has recently been shown that PARP-1 is a
      novel co-activator of TCF-4/beta-catenin-evoked gene transactivation and may play
      a role in colorectal carcinogenesis. The aim of this study was to examine the
      PARP-1 expression and determine whether it is correlated with the expression of
      beta-catenin and its target genes such as c-myc, cyclin D1 and matrix
      metalloproteinase (MMP)-7 in the early stage of sporadic colorectal
      carcinogenesis. Using the semi-quantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR), 91 colorectal tumours, including 65 adenomas and 26
      submucosal (pT1) cancers, were analysed for the expression of PARP-1, beta
      catenin, c-myc, cyclin D1 and MMP-7. Immunohistochemical analysis of PARP-1 and
      beta-catenin was also performed. PARP-1 mRNA overexpression was detected in 64
      (70.3%) of the 91 tumours. PARP-1 overexpression was significantly correlated
      with tumour size and histopathology. Overexpression of beta-catenin, c-myc,
      cyclin D1 and MMP-7 mRNA expression was observed in 39.6%, 78.0%, 83.5% and 72.5%
      of the 91 tumours, respectively. PARP-1 overexpression was correlated
      significantly with overexpression of beta-catenin, c-myc, cyclin D1 and MMP-7.
      Correlation of PARP-1 expression with beta-catenin overexpression was also
      demonstrated by immunohistochemistry. The results suggest that PARP-1, in
      conjunction with beta-catenin, c-myc, cyclin D1 and MMP-7, plays an important
      role in the early stage of colorectal carcinogenesis.

PMID- 16809032
TI  - Prognostic factors for progression of childhood optic pathway glioma: a
      systematic review.
AB  - A systematic literature review was carried out to evaluate best existing evidence
      on prognostic factors for progression of childhood optic pathway glioma.
      Databases were searched for relevant articles and articles selected independently
      by two authors. Information about study design, population, treatment, outcome
      and prognostic analysis were abstracted and the quality of each article was
      assessed. A total of 23 articles met the inclusion criteria. Many studies had
      important methodological limitations, regarding external and internal validity.
      Eleven studies evaluated possible prognostic factors in a multivariate analysis.
      Three high-quality studies indicated age<1 year as an independent prognostic
      factor for a worse progression-free survival. Three studies with multivariate
      analysis, including one high-quality study, found that children with
      neurofibromatosis type 1 (NF-1) have a better progression-free survival than
      those without NF-1. Two studies with multivariate analysis found tumour site to
      be a prognostic factor, both with some methodological limitations. In conclusion,
      this systematic review demonstrates that only a few of the prognostic factors
      proposed have been proven to be clinically relevant. Age<1 year is a clear and
      independent prognostic factor for progression-free survival. Other prognostic
      factors, such as NF-1, tumour site and others, are suggested, but are still
      without solid evidence and need further high-quality studies to be clearly
      proven.

PMID- 16809033
TI  - Synthesis of cell-permeable peptide nucleic acids and characterization of their
      hybridization and uptake properties.
AB  - Guanidine-based peptide nucleic acid (GPNA) monomers and oligomers containing all
      four natural (adenine (A), cytosine (C), guanine (G), and thymine (T)) and two
      unnatural (2-thiouracil (sU) and 2,6-diaminopurine (D)) nucleobases have been
      synthesized. Thermal denaturation study showed that GPNA oligomers containing
      alternate D-backbone configuration bind sequence-specifically to DNA and, when
      incubated with mammalian cells, localized specifically to the endoplasmic
      reticulum (ER).

PMID- 16809034
TI  - Hydrazides of clozapine: a new class of D1 dopamine receptor subtype selective
      antagonists.
AB  - Acylated and aroylated hydrazinoclozapines are highly potent dopamine D(1)
      antagonists that show remarkable selectivity over other dopamine receptors. The
      most potent compound in this series is the 2,6-dimethoxybenzhydrazide 33 with a
      D(1)K(i) of 1.6 nM and 212-fold selectivity over D(2) receptor.

PMID- 16809035
TI  - Correlation between brain/plasma ratios and efficacy in neuropathic pain models
      of selective metabotropic glutamate receptor 1 antagonists.
AB  - We have discovered a novel, potent, and selective triazafluorenone series of
      metabotropic glutamate receptor 1 (mGluR1) antagonists with efficacy in various
      rat pain models. Pharmacokinetic and pharmacodynamic profiles of these
      triazafluorenone analogs revealed that brain/plasma ratios of these mGluR1
      antagonists were important to achieve efficacy in neuropathic pain models. This
      correlation could be used to guide our in vivo SAR (structure-activity
      relationship) modification. For example, compound 4a has a brain/plasma ratio of
      0.34, demonstrating only moderate efficacy in neuropathic pain models. On the
      other hand, antagonist 4b with a brain/plasma ratio of 2.70 was fully efficacious
      in neuropathic pain models.

PMID- 16809036
TI  - Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and
      II, and the transmembrane, tumor-associated isozymes IX and XII with substituted
      aromatic sulfonamides activatable in hypoxic tumors.
AB  - Some 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones
      were prepared and investigated as inhibitors of four isoforms of the zinc enzyme
      carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I and II (cytosolic enzymes),
      and the tumor-associated CA IX and XII. Some mercaptans led to a consistent
      increase of inhibitory power (52.8- to 243-fold) over the corresponding oxidized
      (S-S type) derivatives, acting as potential hypoxia-activatable drugs.

PMID- 16809037
TI  - Macrolactin N, a new peptide deformylase inhibitor produced by Bacillus subtilis.
AB  - A new 24-membered ring lactone, macrolactin N, was isolated from a culture broth
      of Bacillus subtilis and its structure was established by various spectral
      analysis. Macrolactin N inhibited Staphylococcus aureus peptide deformylase with
      an IC50 value of 7.5 microM and also showed antibacterial activity against
      Escherichia coli and S. aureus.

PMID- 16809038
TI  - Dermatomyositis, lobar panniculitis and inflammatory myopathy with abundant
      macrophages.
AB  - Dermatomyositis (DM) is a rare treatable muscle disorder with a reported
      favorable outcome in most patients. A localized skin/muscle involvement in a DM
      patient raises questions of definition and causes such as lymphoma, or relapse.
      We describe here a young treated DM patient who presented a focal biopsy-proven
      destructive myositis and dermatitis restricted to the left thigh 15 months after
      the onset of a treated dermatomyositis. There was evidence of subcutaneous
      lobular panniculitis, somewhat resembling cytophagic histocytic panniculitis
      associated with a focal inflammatory myopathy with abundant macrophages that
      destroyed the sartorius muscle. Mild signs of hemophagocytosis and T-CD3
      lymphocytosis were present in the bone marrow, but no monoclonal T-lymphocyte
      expansion was observed, as searched by autoradiography of the totality of TcR
      Vgamma families. The patient improved with prednisone and azathioprine. We
      conclude that this focal complication suggests a continuum between
      dermatomyositis, CHP, and IMAM, the three syndromes where T-cell activation plays
      an important role.

PMID- 16809039
TI  - Safe and efficacious probiotics: what are they?
AB  - Each year, >20 billion doses of probiotics are used by healthy people and by
      those diagnosed with a range of medical conditions. Compared to many
      pharmaceutical agents, probiotics are well tolerated and extremely safe, and
      serious adverse effects rarely occur. Nevertheless, as many new researchers enter
      the field and companies launch "probiotic" products, it is essential that
      standards are set for naming a product "probiotic" to show that it meets an
      acceptable level of safety and efficacy, and to understand the strengths and
      limitations of its activity. In this Opinion article, recommendations are made
      based upon the current understanding of scientific, clinical and regulatory
      issues, with a special focus on safety.

PMID- 16809040
TI  - Sporting and physical activity following Oxford medial unicompartmental knee
      arthroplasty.
AB  - The purpose of this study was to evaluate and assess the sporting and physical
      activities of patients who had undergone an Oxford medial unicompartmental knee
      arthroplasty (UKA). Seventy-six patients who underwent a UKA between 2000 and
      2003 were reviewed. Demographic data such as age, sex and comorbidities were
      recorded. University of California Los Angeles (UCLA) activity level ratings and
      Oxford knee scores were determined for each patient. The sporting and physical
      activities of all patients' pre- and post-operatively were recorded. The mean age
      of patients was 64 years (range 49-81) at surgery and 66 years (range 53-82) at
      review. The mean follow up time was 18 months (range 4-46). Following surgery
      there was a significant improvement in UCLA activity level scores from 4.2 to 6.5
      (Wilcoxon Matched-pairs Signed-rank Test, p<0.01). Forty-two patients (64%)
      regularly participated in sport before they became symptomatic with significant
      knee pain, and thirty-nine patients (59%) regularly participated in sports after
      surgery. In total 93% of patients successfully returned to their regular sporting
      and physical activities following surgery. The published long-term survivorship
      of the Oxford UKA has given surgeons increasing confidence to use the prosthesis
      on a younger generation of patients. Our study has demonstrated that this
      population of patients is extremely active. A more detailed study is required to
      evaluate the long-term effects of sporting activity on the Oxford UKA.

PMID- 16809041
TI  - Biochemical and functional characterization of an L-amino acid oxidase isolated
      from Bothrops pirajai snake venom.
AB  - In this work we describe the isolation of a new l-amino acid oxidase (LAAO)
      referred to as BpirLAAO-I from Bothrops pirajai snake venom, which was highly
      purified using a combination of molecular exclusion, affinity, and hydrophobic
      chromatography steps. BpirLAAO-I homodimeric acid glycoprotein (approximate Mr
      and pI of 130,000 and 4.9, respectively) displays high specificity toward
      hydrophobic/aromatic amino acids, while deglycosylation does not alter its
      enzymatic activity. The N-terminal LAAO sequence of its first 49 amino acids
      presented a high similarity between a amino acid sequence with other LAAOs from:
      Bothrops spp., Crotalus spp., Calloselasma rhodostoma, Agkistrodon spp.,
      Trimeresurus spp., Pseudechis australis, Oxyuranus scutellatus, and Notechis
      scutatus. BpirLAAO-I induces time-dependent platelet aggregation, mouse paw
      edema, cytotoxic activity against Escherichia coli, Pseudomonas aeruginosa,
      Leishmania sp., and tumor cells, and also a typical fago (M13mp18) DNA
      fragmentation. Platelet aggregation, leishmanicidal and antitumoral activities
      were reduced by catalase. Thus, BpirLAAO-I is a multifunctional protein with
      promising biotechnological and medical applications.

PMID- 16809042
TI  - The introduction of fluorine atoms or trifluoromethyl groups in short cationic
      peptides enhances their antimicrobial activity.
AB  - The effect of introducing fluorine atoms or trifluoromethyl groups in either the
      peptidic chain or the C-terminal end of cationic pentapeptides is reported. Three
      series of amide and ester peptides were synthesised and their antimicrobial
      properties evaluated. An enhanced activity was found in those derivatives whose
      structure contained fluorine, suggesting an increase in their hydrophobicity.

PMID- 16809043
TI  - Antitumor agents 251: synthesis, cytotoxic evaluation, and structure-activity
      relationship studies of phenanthrene-based tylophorine derivatives (PBTs) as a
      new class of antitumor agents.
AB  - Polar phenanthrene-based tylophorine derivatives (PBTs) were designed,
      synthesized and evaluated as potential antitumor agents. These compounds contain
      a core phenanthrene structure and can be synthesized efficiently in excellent
      yield. The newly synthesized PBTs were evaluated for cytotoxic activity against
      the A549 human cancer cell line. Among them, N-(2,3-methylenedioxy-6-methoxy
      phenanthr-9-ylmethyl)-L-2-piperidinemethanol (34) and N-(2,3-methylenedioxy-6
      methoxy-phenanthr-9-ylmethyl)-5-aminopentanol (28) showed the highest potency
      with IC50 values of 0.16 and 0.27 microM, respectively, which are comparable to
      those of currently used antitumor drugs. A structure-activity relationship (SAR)
      study was also explored to facilitate the further development of this new
      compound class.

PMID- 16809044
TI  - Diverse signals converge at MAPK cascades in plant.
AB  - Mitogen-activated protein kinases (MAPKs) are important signal transducing
      enzymes that connects diverse receptors/sensors to a wide range of cellular
      responses in mammals, yeasts and plants. In recent years, a large number of
      different components of plant MAPK cascades were isolated. Molecular and
      biochemical studies have revealed that plant MAPKs play important role in the
      response to a broad variety of biotic and abiotic stresses, including wounding,
      pathogen infection, temperature, drought, salinity, but also in the signaling of
      plant hormones and the cell division. This review briefly summaries the recent
      research results about the cross-talk and complexity of MAP kinase cascades in
      plant obtained from functional analyses.

PMID- 16809045
TI  - MALDI analysis of oligonucleotides directly from montmorillonite.
AB  - Oligonucleotides synthesized on a montmorillonite catalyst were analyzed
      directly. By mixing the catalyst with a matrix (2,4,6-trihydroxyacetophenone or 6
      aza-2-thiothymine) and dibasic ammonium citrate, higher molecular weight products
      were detected compared with "classical" methods such as gel electrophoresis and
      HPLC with UV as a detector. The oligomers (30-mers and higher) were detected by
      mass spectrometry even though their concentration was less than 10(-4)% of the
      total content of the RNA. This method is different from the (MALDI) analysis of
      the eluates from montmorillonite, which otherwise requires desalting. Placing
      reaction mixtures with a high concentration of buffers on homoionic, preferably
      Li-containing, montmorillonite does not require desalting.

PMID- 16809046
TI  - Side-chain fragmentation of alkylated cysteine residues in electron capture
      dissociation mass spectrometry.
AB  - The recent development of novel fragmentation processes based on either electron
      capture directly or transfer from an anion show great potential for solving
      problems in proteomics that are intractable by the more widely employed thermal
      based fragmentation processes such as collision induced dissociation. The
      dominant fragmentation occurring upon electron capture dissociation of peptides
      is cleavage of N-C alpha bonds in the peptide backbone to form c and z* ions. In
      the case of disulfide-linked peptides, it has also been shown that electron
      capture on one of the cystine sulfur atoms is favored, resulting in cleavage of
      the disulfide bond. In this study, we report that electron capture on the sulfur
      of alkylated cysteine residues is also a dominant process, causing cysteine side
      chain loss from z* ions.

PMID- 16809047
TI  - Formation of anionic peptide radicals in vacuo.
AB  - In this paper, we demonstrate for the first time the formation of radical anionic
      peptides [M - 2H]*- through a one-electron transfer mechanism upon low-energy
      collision-induced dissociation (CID) of gas-phase singly charged
      [Mn(III)(salen)(M - 2H)]*- complex ions [where salen is N,N'
      ethylenebis(salicylideneiminato) and M is an angiotensin III derivative]. The
      types of fragment ions formed from [M - 2H]*- share some similarities with those
      from the cationic radical peptides M*+ and [M + H]*2+, but differ significantly
      from those of the corresponding deprotonated peptides [M - H]-. Fragmentation of
      [M - 2H]*- radical anionic angiotensin III derivatives leads preferentially to
      product ions of side-chain cleavage of amino acid residues, z-type and minor x
      type fragment ions, most of which are types rarely observed in low-energy CID
      spectra of deprotonated analogs. The degree of competitive dissociation of the
      complexes is highly dependent on the nature of the substituted salen derivatives.
      The yields of anionic peptide radicals were enhanced to the greatest extent when
      electron withdrawing groups were positioned at the 5 and 5' positions, but the
      effect was rather modest when such groups resided at the 3 and 3' positions.
      Substituting a cyclohexyl unit of a salen with phenyl or naphthyl moieties at the
      8 and 8' positions also facilitated electron-transfer pathways.

PMID- 16809048
TI  - The zebrafish as a model system for assessing the reinforcing properties of drugs
      of abuse.
AB  - Recent reports make use of the zebrafish to study complex behavior such as
      addiction, anxiety, or learning and memory. We have established reliable tests
      and appropriate controls to measure these behavioral parameters in the zebrafish
      adult. Our assays are robust enough to permit the detection of dominant mutations
      affecting drug-induced reward, and therefore can be used in forward genetic
      screens. We provide the reader with the technical details of these tests, as well
      as their appropriate and crucial, although often overlooked, control assays. In
      particular, our results make it possible to use the zebrafish as a promising
      model to identify new genetic components of the reward pathway, or other
      measurable behaviors.

PMID- 16809049
TI  - Identification of the dominant translation start site in the attB1 sequence of
      the pET-DEST42 Gateway vector.
AB  - Gateway technology is a powerful system for converting a single entry vector into
      a wide variety of expression vectors. We expressed recombinant influenza matrix
      protein M1 (FMP), a potent antigen for cytotoxic T cells, using the Gateway
      vector pET-DEST42 containing the FMP cDNA, and purified the expressed FMP as a
      single 32 kDa recombinant protein. N-terminal and internal protein sequencing,
      however, showed that the recombinant FMP contained an extra 10 amino acids fused
      to the N-terminal of native FMP. Further investigation of the DNA sequence
      adjacent to the 5'-FMP cDNA indicated that the "TTG" in the attB1 site (30 bp
      upstream of the "ATG" in the 5'-FMP cDNA) behaved as a dominant translation start
      site, resulting in a 10 amino acid extension of the recombinant FMP. Thus, it is
      possible that recombinant proteins produced by this Gateway vector contain
      unexpected vector-derived peptides, which may affect experimental outcomes.

PMID- 16809050
TI  - Expression in E. coli and purification of the nucleoside diphosphate kinase b
      from Leishmania major.
AB  - Leishmaniasis is considered by the World Health Organization to be the second
      most important disease caused by a protozoan parasite. Biochemical and molecular
      biology studies can help in the understanding of the biology of the Leishmania
      parasite. All protozoan parasites, including Leishmania, are unable to synthesize
      purines de novo, and nucleoside diphosphate kinases (NDK) are involved in the
      salvage pathway by which free purines are converted to nucleosides and
      subsequently to nucleotides. In this report, we describe the cloning of NDK
      coding-sequence from Leishmania major, the expression of the enzyme containing a
      His(6)-tag in Escherichia coli, and purification of the catalytically active
      native protein by affinity chromatography using Ni-NTA resin.

PMID- 16809051
TI  - Purification and characterization of the second Streptomyces phospholipase A2
      refolded from an inclusion body.
AB  - A secreted phospholipase A(2) (PLA(2)) from Streptomyces violaceoruber A-2688,
      previously identified by us, is the first PLA(2) identified in prokaryotes.
      Genome sequence data of Streptomyces coelicolor A3(2) indicates that the
      bacterium carries two genes encoding hypothetical PLA(2)s, which exhibit 100 and
      78% identity, respectively, to the S. violaceoruber PLA(2). In this study, we
      named the former and latter proteins as the first and second PLA(2)s,
      respectively. When the second PLA(2) was expressed in Escherichia coli cells, it
      formed an inclusion body. The present study demonstrates a method to purify it to
      homogeneity without the disappearance of the enzymatic activity: the inclusion
      body was washed with sodium deoxycholate and dissolved in the presence of 2 M
      urea at pH 12, then refolded by the dilution method. The refolding of enzyme was
      confirmed by the circular dichroism spectrum. The second PLA(2) purified to
      homogeneity had the same specific activity as that of the S. violaceoruber PLA(2)
      and the yield was approximately 6.8 mg/L culture. The second PLA(2) exhibits
      similar enzymatic properties to the S. violaceoruber PLA(2), except that the
      former enzyme does not utilize phophatidic acid as a substrate. The surface
      electrostatic potential of the S. coelicolor PLA(2) model, which is created by
      the computer-homology modeling, suggests that the positively charged surface of
      the enzyme does not affect the substrate specificity.

PMID- 16809052
TI  - White matter volume and concentration reductions in adolescents with history of
      very preterm birth: a voxel-based morphometry study.
AB  - Very preterm birth (VPTB) is an important risk factor for white matter (WM)
      damage. We used voxel-based morphometry (VBM) to examine regional WM brain
      abnormalities in 50 adolescents with antecedents of very preterm birth (VPTB)
      without evidence of WM damage on T2-weighted MRI. This group was compared with a
      group of 50 subjects born at term and matched for age, handedness and socio
      cultural status. We also examined the relationship between WM changes and
      gestational age (GA) and weight (GW) at birth in VPTB subjects. Both modulated
      and unmodulated VBM analyses showed significant abnormalities in several WM brain
      regions in the VPTB group, involving all the cerebral lobes. However, density
      analyses (unmodulated data) mainly identified periventricular damage and the
      involvement of the longitudinal fascicles while volume analyses (modulated data)
      detected WM decreases in regions distant from the ventricular system, located at
      the origin and end of the long fascicles. A significant correlation was found
      between WM decreases and both GA and GW in various brain regions: the lower the
      GA and GW, the lower the WM integrity. This study supports the current view that
      widespread white matter impairment is associated with immature birth.

PMID- 16809053
TI  - The surround inhibition determines therapy-induced cortical reorganization.
AB  - Rehabilitation can induce cortical reorganization in chronic stroke patients. In
      this study we investigated the mechanisms underlying treatment-associated
      plasticity. Eight patients with a stroke >6 months earlier participated in a 4
      week period of physiotherapy based on a forced use concept. Before and after
      treatment, focal transcranial magnetic stimulation over the affected hemisphere
      was used to assess the motor output map of the paretic first dorsal interosseous
      muscle. Using a paired pulse paradigm, intracortical inhibition was investigated
      at the center of the cortical output map (CoG) and one cm anterior, posterior,
      lateral and medial of that position. Motor function was evaluated with the Motor
      Activity Log and the Wolf Motor Function Test. After therapy, the cortical
      representation size of the affected hand muscle was increased. In each patient,
      the CoG moved in the direction where intracortical inhibition had been lowest
      prior to therapy. Significant correlations were found between motor function
      tests and changes of output map size and CoG shifts, respectively. We conclude
      that treatment-associated cortical reorganization is influenced by the
      distribution of inhibitory properties within the representation area prior to
      therapy, since the CoG moved in the direction of lowest inhibition. The
      correlations between motor functions and electrophysiological results indicate a
      functional relevance of the observed reorganization pattern.

PMID- 16809054
TI  - Sensory gating of auditory evoked and induced gamma band activity in intracranial
      recordings.
AB  - Oscillatory activity in the gamma band range (30-50 Hz) and its functional
      relation to auditory evoked potentials (AEPs) is yet poorly understood. In the
      current study, we capitalized on the advantage of intracranial recordings and
      studied gamma band activity (GBA) in an auditory sensory gating experiment.
      Recordings were obtained from the lateral surface of the temporal lobe in 34
      epileptic patients undergoing presurgical evaluation. Two kinds of activity were
      differentiated: evoked (phase locked) and induced (not phase locked) GBA. In 18
      patients, an intracranial P50 was observed. At electrodes with maximal P50,
      evoked GBA occurred with a similar peak latency as the P50. However, the
      intensities of P50 and evoked GBA were only modestly correlated, suggesting that
      the intracranial P50 does not represent a subset of evoked GBA. The peak
      frequency of the intracranial evoked GBA was on average relatively low
      (approximately 25 Hz) and is, therefore, probably not equivalent to
      extracranially recorded GBA which has normally a peak frequency of approximately
      40 Hz. Induced GBA was detected in 10 subjects, nearly exclusively in the region
      of the superior temporal lobe. The induced GBA was increased after stimulation
      for several hundred milliseconds and encompassed frequencies up to 200 Hz. Single
      trial analysis revealed that induced GBA occurred in relatively short bursts
      (mostly <<100 ms), indicating that the duration of the induced GBA in the
      averages originates from summation effects. Both types of gamma band activity
      showed a clear attenuation with stimulus repetition.

PMID- 16809055
TI  - The role of hippocampal sclerosis in antiepileptic drug-related depression in
      patients with epilepsy: a study on levetiracetam.
AB  - OBJECTIVE: Hippocampal sclerosis (HS) has been described as a relevant factor for
      the development of topiramate-related depression and cognitive deficits. The aim
      of our study was to clarify whether patients with temporal lobe epilepsy (TLE)
      and HS were also at risk during therapy with levetiracetam (LEV). METHODS: Data
      of 156 patients was analysed: 78 with TLE and HS and 78 with TLE and normal MRI
      matched for age, starting dose and titration schedule of LEV. Patients were
      selected from a population of consecutive patients started on LEV between 2000
      and 2002. RESULTS: No differences were observed in prevalence of cognitive
      adverse events and depression between the two groups. CONCLUSIONS: LEV treatment
      is not associated with cognitive adverse events and depression in patients with
      hippocampal sclerosis.

PMID- 16809056
TI  - The attention-intention-effort pathway in the development of psychophysiologic
      insomnia: a theoretical review.
AB  - Psychophysiologic insomnia (PI) is the most common form of persistent primary
      insomnia. Its 'behavioral phenotype', comprising elements such as conditioned
      arousal, sleep-incompatible behavior and sleep preoccupation, has not changed
      markedly across several generations of diagnostic nosology. Moreover, a
      substantial outcome literature demonstrates that PI can be treated effectively
      using a range of psychological interventions. It seems evident that behavioral
      and cognitive factors play a part. What is less clear is exactly how PI develops
      and what are its crucial maintaining factors. This paper proposes an explanatory
      model, that we call the attention-intention-effort pathway. The argument is that
      sleep normalcy is a relatively automatic process. Consequently, it is vulnerable,
      and may be inhibited, by focused attention and by direct attempts to control its
      expression. Drawing upon parallels in the literature on adult psychopathology,
      and upon recent clinical and experimental studies on insomnia, the evidence for
      this pathway is considered and a research agenda is outlined. In particular,
      computerized tests of cognitive bias are seen as offering an objective means of
      appraising mental processes in insomnia. These may be applied concurrently with
      somatic measurements in future studies to better understand this common psycho
      physiologic condition.

PMID- 16809057
TI  - CAP, epilepsy and motor events during sleep: the unifying role of arousal.
AB  - Arousal systems play a topical neurophysiologic role in protecting and tailoring
      sleep duration and depth. When they appear in NREM sleep, arousal responses are
      not limited to a single EEG pattern but are part of a continuous spectrum of EEG
      modifications ranging from high-voltage slow rhythms to low amplitude fast
      activities. The hierarchic features of arousal responses are reflected in the
      phase A subtypes of CAP (cyclic alternating pattern) including both slow arousals
      (dominated by the <1Hz oscillation) and fast arousals (ASDA arousals). CAP is an
      infraslow oscillation with a periodicity of 20-40s that participates in the
      dynamic organization of sleep and in the activation of motor events. Physiologic,
      paraphysiologic and pathologic motor activities during NREM sleep are always
      associated with a stereotyped arousal pattern characterized by an initial
      increase in EEG delta power and heart rate, followed by a progressive activation
      of faster EEG frequencies. These findings suggest that motor patterns are already
      written in the brain codes (central pattern generators) embraced with an
      automatic sequence of EEG-vegetative events, but require a certain degree of
      activation (arousal) to become visibly apparent. Arousal can appear either
      spontaneously or be elicited by internal (epileptic burst) or external (noise,
      respiratory disturbance) stimuli. Whether the outcome is a physiologic movement,
      a muscle jerk or a major epileptic attack will depend on a number of ongoing
      factors (sleep stage, delta power, neuro-motor network) but all events share the
      common trait of arousal-activated phenomena.

PMID- 16809058
TI  - alpha2-adrenoceptor agonists as nasal decongestants.
AB  - Nasal congestion, one of the major disease features of rhinitis, is induced by
      the filling of venous sinusoids causing mucosal engorgement with resultant
      obstruction of nasal airflow. The only available drugs that directly target the
      underlying vascular features driving nasal obstruction are the sympathomimetic
      alpha-adrenoceptor agonists due to their vasoconstrictor action. However,
      standard decongestants are nonselective alpha-adrenoceptor agonists, which have
      the potential for side-effects liabilities such as hypertension, stroke, insomnia
      and nervousness. In the present study, the effects of nonsubtype selective
      alpha(2)-adrenoceptor agonists BHT-920 and PGE-6201204 were evaluated in several
      isolated nasal mucosa contractile bioassays including dog, pig and monkey, and in
      a real-time tissue contractility assay using isolated pig nasal explants for BHT
      920. The decongestant activity of PGE-6201204 was evaluated in vivo in a cat
      model of experimental congestion. Our results showed that alpha(2)-adrenoceptor
      agonists (1) contract nasal mucosa of different species, (2) exert a preferential
      vasoconstrictor effect on the capacitance vessels (veins and sinusoids), and (3)
      elicit decongestion. In conclusion, a selective alpha(2)-adrenoceptor agonist
      causing constriction preferentially in the large venous sinusoids and veins of
      nasal mucosa and producing nasal decongestion is expected to show efficacy in the
      treatment of nasal congestion without the characteristic arterio-constrictor
      action of the standard nonselective sympathomimetic decongestants.

PMID- 16809059
TI  - The place embeddedness of social care: restructuring work and welfare in
      Mackenzie, BC.
AB  - The concept of social care is valuable in examining how responsibilities for
      social support are distributed amongst private, public and voluntary interests.
      We argue that social care is embedded in place, by which we mean the social
      relations that determine who provides what are closely connected with the
      physically bounded settings of meaning and interaction in which these activities
      and relations occur. To illustrate the usefulness of these conceptions, we
      present a case study of the restructuring of work and welfare arrangements in
      Mackenzie, British Columbia, a remote and resource-dependent community in the
      province's northern interior.

PMID- 16809060
TI  - Inter-rater and test-retest reliability: methods and results for the neighborhood
      observational checklist.
AB  - The popularity of direct or systematic social observation as a method to evaluate
      the mechanisms by which neighborhood environments impact health and contribute to
      health disparities is growing. The development of measures with adequate inter
      rater and test-retest reliability is essential for this research. In this paper,
      based on our experiences conducting direct observation of neighborhoods in
      Detroit, MI, we describe strategies to promote high inter-rater and test-retest
      reliability and methods to evaluate reliability. We then present the results and
      discuss implications for future research efforts using direct observation in four
      areas: methods to evaluate reliability, instrument content and design, observer
      training, and data collection.

PMID- 16809061
TI  - Nomenclature for HKT transporters, key determinants of plant salinity tolerance.

PMID- 16809062
TI  - Protein kinase C regulatory domains: the art of decoding many different signals
      in membranes.
AB  - Protein kinase C (PKC) is a member of a family of Ser/Thr phosphotransferases
      that are involved in many cellular signaling pathways. These enzymes possess two
      regulatory domains, C1 and C2, that are the targets of different second
      messengers. The purpose of this review is to describe in molecular terms the
      diverse mechanisms of activation of PKCs in the light of very significant
      advances made in this field over recent years. The role of some critical amino
      acid residues concerning activation of the enzymes and their location within
      known structures of isolated domains will be presented. For example, the recently
      deduced 3D structures of the C2 domains show that these domains can additionally
      act as PtdIns(4,5)P(2)-binding or phosphotyrosine-binding modules depending on
      the isoenzyme. All these capacities to play different roles in the cell wide web
      of signals underline the notion that we are dealing with a multifunctional family
      of enzymes which, after 30 years of investigation, we are just beginning to
      understand.

PMID- 16809063
TI  - Skill acquisition in tennis: research and current practice.
AB  - Common to most tennis players is the desire to improve performance. Equipped with
      the necessary motivation, these players can spend countless hours rehearsing
      tennis' skills under the guidance of a coach. Often, these practices feature
      repetitious hitting, with little consideration given to the actual context in
      which the game's skills are expressed. Alternatively, training sessions that
      amount to little more than poorly structured game-play, devoid of any specific
      goals or objectives, are also discernible. Either way, player learning and long
      term performance are unlikely to be optimised. So, where tennis coaches have long
      relied on certain instructional approaches and types of practices to enhance
      player performance, their efficacy is uncertain. Indeed, a growing body of
      research suggests that players stand to benefit from the earlier introduction of
      variable and random practices and feedback that is more intrinsic in nature
      rather than time-honoured overly prescriptive coaching. This review considers
      contemporary skill acquisition research in relation to current tennis coaching
      practice.

PMID- 16809064
TI  - Patterns of fatigue during a course of chemotherapy: results from a multi-centre
      study.
AB  - Fatigue is a highly prevalent condition among patients with cancer affecting
      between 70% and 100% and patients describe their fatigue experiences as the most
      distressing of symptoms. However, the management of fatigue is complicated by our
      current lack of understanding of its pathophysiology. This study aimed to gain an
      insight into the longitudinal fatigue experiences of patients receiving
      chemotherapy. A convenience sample of patients receiving chemotherapy (n=249)
      were recruited and recorded their fatigue experiences using a paper questionnaire
      for 14 consecutive days following each cycle of chemotherapy. Fatigue was
      reported in 57% of all completed questionnaires. Patients report fatigue as a
      relatively constant presence following chemotherapy. Moreover, fatigue
      experiences increase over consecutive cycles of chemotherapy. This study supports
      the existing evidence illustrating fatigue as a significant problem for patients
      with cancer and provides new data demonstrating patterns of fatigue over the
      duration of a course of chemotherapy. Understanding this experience of fatigue
      should prompt health professionals providing care for this patient population to
      seek and test a range of management strategies to help patients maintain their
      quality of life during cancer treatment.

PMID- 16809065
TI  - Why do B cells mutate their immunoglobulin receptors?
AB  - B cells have the unique ability to acquire large numbers of point mutations in
      the variable segment of rearranged immunoglobulin (Ig) genes during a germinal
      center reaction. It is broadly accepted that somatic hypermutation (SHM) and
      affinity maturation are required to generate memory B cells and to produce
      antibodies capable of accomplishing the host defense functions of the humoral
      component of the adaptive immune system. However, several studies illustrate that
      low-avidity interactions between antigen and the B-cell receptor can induce
      deletion, receptor editing and a T-dependent immune response, suggesting that the
      high-avidity binding of antigen is not essential. If enhanced antigen binding is
      not essential for immune responses, what is the purpose of SHM? An alternative
      benefit of SHM might be to enhance the ability of B cells to track antigens
      expressed by rapidly mutating microorganisms.

PMID- 16809066
TI  - AKAP signaling complexes: getting to the heart of the matter.
AB  - Subcellular compartmentalization of protein kinases and phosphatases through
      their interaction with A-kinase anchoring proteins (AKAPs) provides a mechanism
      to control signal transduction events at specific sites within the cell. Recent
      findings suggest that these anchoring proteins dynamically assemble different
      cAMP effectors to control the cellular actions of cAMP spatially and temporally.
      In the heart, signaling events such as the onset of cardiac hypertrophy are
      influenced by muscle-specific mAKAP signaling complexes that target protein
      kinase A (PKA), the cAMP-responsive guanine-nucleotide exchange factor EPAC and
      cAMP-selective phosphodiesterase 4 (PDE4). Mediation of signaling events by AKAPs
      might also have a role in the control of lipolysis in adipocytes, where insulin
      treatment reduces the association of AKAPs with G-protein-coupled receptors.
      These are only two examples of how AKAPs contribute to specificity in cAMP
      signaling. This review will explore recent development that illustrates the role
      of multiprotein complexes in the regulation of cAMP signaling.

PMID- 16809067
TI  - Tore Godal: pragmatic opportunist championing global public health.
AB  - Recently retired as head of the Global Alliance for Vaccines and Immunization
      (GAVI) secretariat and as a health advisor to leading global entities, Tore Godal
      is now a Special Advisor to the Norwegian Prime Minister. He is nevertheless
      continuing to fight for better global health, cogently articulating the needs of
      the world's poor and disadvantaged. He is a leading leprosy expert, ex-director
      of the world's premier agency for research and training in tropical diseases,
      instigator and prime mover of some global innovative public-private health sector
      partnerships, adept fund mobilizer, and advocate of the 'let's get it done'
      school of leadership. Few individuals are, therefore, more experienced or better
      suited for such a crucial and much-needed role.

PMID- 16809068
TI  - Finding the missing link between ictal bradyarrhythmia, ictal asystole, and
      sudden unexpected death in epilepsy.
AB  - Basic science studies of the human brain have supported the cortical
      representation of cardiovascular responses, including heart rate variability.
      Clinical observations of ictal bradyarrhythmia may be mechanistically explained
      by the influence of the central autonomic network, although the localization and
      lateralization issues need to be considered in the light of patterns of seizure
      spread, hand dominance, and presence of lesions. Ictal bradyarrhythmia also
      offers a mechanistic explanation of sudden unexpected death in epilepsy (SUDEP),
      though it may explain only some but not all cases of SUDEP. The missing links are
      (1) clinical evidence of common factors shared by patients with ictal
      bradyarrhythmia and patients who die from SUDEP, (2) evidence of arrhythmia as a
      risk factor for SUDEP from epidemiological studies, and, (3) determination of the
      importance of ictal bradyarrhythmia in SUDEP with respect to other proposed
      mechanisms including apnea and intrinsic cardiac abnormalities. There remains a
      need to review the seizure mechanisms in cases of SUDEP and to step up the amount
      of concurrent ECG/intracranial EEG analysis in both ictal bradyarrhythmia and
      SUDEP cases.

PMID- 16809069
TI  - Exogenous glycine partially attenuates homocysteine-induced apoptosis and
      membrane peroxidation in chick embryos.
AB  - The effects of exogenous glycine on homocysteine (HoCys)-induced reductions in
      chick (Gallus gallus) embryo viability, HoCys-induced increases in brain and
      hepatic membrane lipid peroxidation, HoCys-induced apoptosis (caspase-3
      activities) in brain and hepatic tissues, and HoCys-induced reductions in brain
      and hepatic S-adenosylemethionine (SAM)/S-adenosylhomocysteine (SAH) levels were
      studied. Exogenous HoCys caused reductions in percent living embryos and
      reductions in embryo masses. Exogenous glycine attenuated these HoCys-induced
      reductions in embryo viability. Brain and liver tissues of HoCys-treated embryos
      exhibited increased caspase-3 activities, increased lipid hydroperoxide (LPO)
      levels, and reduced levels of long-chain polyunsaturated membrane fatty acids.
      While exogenous glycine attenuated HoCys-induced changes in brain caspase-3
      activities, brain LPO levels, and brain membrane PUFA levels, exogenous glycine
      was less effective in attenuating HoCys-induced changes in hepatic caspase-3
      activities and hepatic membrane PUFA levels. HoCys-induced reductions in SAM/SAH
      ratios were observed in brains and livers. Exogenous glycine attenuated HoCys
      induced reductions in brain SAM/SAH. However, glycine was unable to attenuate
      HoCys-induced reductions in hepatic SAM/SAH levels.

PMID- 16809070
TI  - Multiple cystic pancreatic neuroendocrine neoplasms in a patient diagnosed via
      endoscopic ultrasound-fine-needle aspiration.

PMID- 16809071
TI  - Atypical giant hepatic hemangiomas with intratumoral hemorrhage.

PMID- 16809072
TI  - Validation of complex interventions in a low back pain trial: selective video
      analysis cross-referenced to clinical case notes.
AB  - INTRODUCTION: Auditing the interventions used in clinical trials to demonstrate
      that treatment protocols were adhered to and that discrete modalities were
      delivered, is essential in establishing internal validity. Pragmatic studies
      involving complex interventions provide a particular challenge. The value of case
      report forms which document individual treatment content relies upon accurate
      recall and recording by the clinician. This report describes a method to validate
      this type of data in a randomised clinical trial, by using video analysis on a
      sample of patient therapist interactions. METHODS: Six physiotherapists used
      standardised case report forms to record the treatment given to 402 patients
      recruited into the two treatment arms of a low back pain clinical trial. An audit
      checklist comprising the principal components of both management approaches was
      designed. Twelve treatment sessions were video recorded. Three independent
      clinicians viewed the recordings, using the checklist to identify the treatment
      content. These data were compared for agreement with the matching case report
      forms. The content of the interventions delivered to all of the trial patients
      was then audited. RESULTS: Agreement between the video observers, and between the
      observers and the case report forms ranged from moderate to very good (kappa=0.45
      0.82). When compared with the video observations, some under-reporting of
      treatment occurred on the case report forms. Overall, 80% of the patients
      received the treatment to which they were allocated. CONCLUSIONS: This study has
      demonstrated that selective use of video recording, cross-referenced to clinical
      case notes may provide a feasible and relatively inexpensive means of
      establishing the internal validity of the interventions used in a pragmatic
      clinical trial.

PMID- 16809073
TI  - Molecular phylogeny of diploid Bulinus sp. (Gastropoda: Planorbidae) populations
      in Cameroon crater lakes.
AB  - Bulinus sp. (2n=36) is a diploid freshwater snail found in Cameroon crater lakes;
      it belongs to a group of medically important freshwater snails. Some members
      (Bulinus truncatus, Bulinus tropicus) of this group had been reported to be
      involved in the transmission of parasites (Schistosoma sp. and Calicophoron
      microbothrium) to human and livestock in tropical Africa. Yet, understanding of
      the evolutionary identity of the diploid snail such as its phylogenetic position
      and the genetic divergence among populations, remains limited. In this study, we
      constructed the molecular phylogeny of Bulinus sp. using sequences of
      mitochondrial cytochrome oxydase subunit 1 (CO-1, 365 nucleotides). Partial
      sequences of CO-1 were obtained and genetic divergences between populations
      estimated after the alignment of 365 nucleotides from each studied population.
      The lack of deep molecular divergences between populations of Bulinus sp. from
      western Cameroon crater lakes may indicate that they belong to the same lineage;
      therefore, it implies that diploid B. truncatus/tropicus complex snail-like in
      Cameroon share a common ancestor. The CO-1 of the three studied populations of
      Bulinus sp., clustered together with other diploid pan-African representatives of
      the B. truncatus/tropicus complex, showed little evidence of genetic
      similarities.

PMID- 16809074
TI  - Electrochemical piezoelectric quartz crystal impedance study on the interaction
      between concanavalin A and glycogen at Au electrodes.
AB  - The carbohydrate research has emerged as a "new frontier" in chemical/biological
      field. The binding of lectin with carbohydrate is one of the important courses of
      life activities. The report studies concanavalin A (Con A)-glycogen interaction
      on gold electrode surfaces by electrochemical piezoelectric quartz crystal
      impedance (EPQCI) method. The piezoelectric quartz crystal (PQC) parameters,
      resonant frequency shift (Deltaf(0)) and the motional resistance change
      (DeltaR(1)), and the electrochemical impedance (EI) parameters, electrolyte
      resistance change (DeltaR(s)) and the double layer capacitance change
      (DeltaC(s)), were measured and discussed simultaneously. Two methods were adopted
      for measuring the Con A-glycogen association. Based on EPQCI measurement during
      Con A reaction with glycogen adsorbed on Au electrode, association constant K(a)
      and the amount of the binding sites s calculated are 1.48 x 10(6) M(-1) and 4.09,
      respectively. Based on single PQC measurement of glycogen reaction with Con A
      assembled on Au electrode, K(a) was estimated to be 1.26 x 10(6) M(-1).

PMID- 16809075
TI  - Etoposide and illegitimate DNA double-strand break repair in the generation of
      MLL translocations: new insights and new questions.
AB  - Faithful repair of chromosomal double-strand breaks (DSBs) is central to genome
      integrity and the suppression of genome rearrangements including translocations
      that are a hallmark of leukemia, lymphoma, and soft-tissue sarcomas [B. Elliott,
      M. Jasin, Double-strand breaks and translocations in cancer, Cell. Mol. Life Sci.
      59 (2002) 373-385; D.C. van Gent, J.H. Hoeijmakers, R. Kanaar, Chromosomal
      stability and the DNA double-stranded break connection, Nat. Rev. Genet. 2 (2001)
      196-206]. Chemotherapy agents that target the essential cellular enzyme
      topoisomerase II (topo II) are known promoters of DSBs and are associated with
      therapy-related leukemias. There is a clear clinical association between previous
      exposure to etoposide and therapy-related acute myeloid leukemia (t-AML)
      characterized by chromosomal rearrangements involving the mixed lineage leukemia
      (MLL) gene on chromosome band 11q23 [C.A. Felix, Leukemias related to treatment
      with DNA topoisomerase II inhibitors, Med. Pediatr. Oncol. 36 (2001) 525-535].
      Most MLL rearrangements initiate within a well-characterized 8.3 kb region that
      contains both putative topo II cleavage recognition sequences and repetitive
      elements leading to the logical hypothesis that MLL is particularly susceptible
      to aberrant cleavage and homology-mediated fusion to repetitive elements located
      on novel chromosome partners. In this review, we will discuss the findings and
      implications of recent attempts to confirm this hypothesis.

PMID- 16809076
TI  - A validated liquid chromatographic-tandem mass spectroscopy method for the
      quantification of abiraterone acetate and abiraterone in human plasma.
AB  - A sensitive and selective LC-MS/MS method has been developed and validated for
      the quantification of abiraterone acetate and its metabolite, abiraterone (an
      androgen biosynthesis inhibitor) in human plasma. Analytes were extracted by SPE
      with cation mixed-mode polymer cartridges. Chromatography was performed on a Luna
      C5 5 microm, 50 mm x 2.1 mm i.d. column, using a mobile phase of 2% propan-2-ol
      in acetonitrile and 10mM ammonium acetate. The assay was linear from 5 to 500 nM
      (r(2)=0.998). The intra- and inter-day coefficients of variation were <13.9% for
      both analytes. This method will be applied to a clinical trial investigating the
      pharmacokinetics of abiraterone acetate and abiraterone in patients with prostate
      cancer.

PMID- 16809077
TI  - Single-based resolution for oligodeoxynucleotides and their phosphorothioate
      modifications by replaceable capillary gel electrophoresis.
AB  - A replaceable capillary gel electrophoretic (replaceable CGE) method was
      developed for the separation of two sets of model compounds of single-stranded
      oligodeoxynucleotide mixtures (18-20 mers), phosphodiester oligodeoxynucleotides
      (PO-ODNs) and their phosphorothioate modifications (PS-ODNs), with equal
      sequences differing in a single base. Polyethylene glycol (PEG) 35000 was chosen
      as the sieving matrix. It was confirmed that PEG polymer solution less influenced
      resolutions of the PS-ODNs compared with those of the PO-ODNs, while acetonitrile
      used as an additive in the system improved the separation significantly. It was
      also noticed that the effect of temperature on separation was much larger than
      that of denaturant urea.

PMID- 16809098
TI  - Involvement of nitrogen-containing compounds in beta-lactam biosynthesis and its
      control.
AB  - Biosynthesis of beta-lactam antibiotics by fungi and actinomycetes is markedly
      affected by compounds containing nitrogen. The different processes employed by
      the spectrum of microbes capable of making these valuable compounds are affected
      differently by particular compounds. Ammonium ions, except at very low
      concentrations, exert negative effects via nitrogen metabolite repression,
      sometimes involving the nitrogen regulatory gene nre. Certain amino acids are
      precursors or inducers, whereas others are involved in repression and, in certain
      cases, as inhibitors of biosynthetic enzymes and of enzymes supplying precursors.
      The most important amino acids from the viewpoint of regulation are lysine,
      methionine, glutamate and valine. Surprisingly, diamines such as diaminopropane,
      putrescine and cadaverine induce cephamycin production by actinomycetes. In
      addition to penicillins and cephalosporins made by fungi and cephamycins made by
      actinomycetes, other beta-lactams are made by actinomycetes and unicellular
      bacteria. These include clavams (e.g., clavulanic acid), carbapenems (e.g.,
      thienamycin), nocardicins and monobactams. Here also, amino acids are precursors
      and inhibitors, but only little is known about regulation. In the case of the
      simplest carbapenem made by unicellular bacteria, i.e., 1-carba-2-em-3-carboxylic
      acid, quorum sensors containing homoserine lactone are inducers.

PMID- 16809099
TI  - Polyunsaturated fatty acids: biotechnology.
AB  - Polyunsaturated fatty acids like EPA and DHA have attracted a great attention due
      to their beneficial effects on human health. At present, fish oil is the major
      source of EPA and DHA. Various alternative sources are being explored to get
      these essential fatty acids. Genes encoding enzymes involved in the biosyntheses
      of PUFAs have been identified, cloned and gene prospecting becomes a novel method
      for enhanced PUFA production. Desaturase and elongase genes have important
      biotechnological appeal from genetic engineering point of view. This review
      highlights the research and results on such enzymes.

PMID- 16809100
TI  - Enzymatic modifications of cephalosporins by cephalosporin acylase and other
      enzymes.
AB  - Semisynthetic cephalosporins are important antibacterials in clinical practice.
      Semisynthetic cephalosporins are manufactured by derivatizing 7
      aminocephalosporanic acid (7-ACA) and its desacetylated form. Microbial enzymes
      such as D-amino acid oxidase, glutaryl-7-ACA acylase and cephalosporin esterase
      are being used as biocatalysts for the conversion of cephalosporin C (CEPH-C) to
      7-ACA and its desacetylated derivatives. Recent developments in the field of
      enzymatic modifications of cephalosporin with special emphasis on group of
      enzymes called as cephalosporin acylase is discussed in this review. Aspects
      related to screening methods, isolation and purification, immobilization,
      molecular cloning, gene structure and expression and protein engineering of
      cephalosporin acylases have been covered. Topics pertaining to enzymatic
      modifications of cephalosporin by D-amino acid oxidase, cephalosporin methoxylase
      and beta-lactamase are also covered.

PMID- 16809101
TI  - Involvement of cell junctions in hepatocyte culture functionality.
AB  - In liver, like in other multicellular systems, the establishment of cellular
      contacts is a prerequisite for normal functioning. In particular, well-defined
      cell junctions between hepatocytes, including adherens junctions, desmosomes,
      tight junctions, and gap junctions, are known to play key roles in the
      performance of liver-specific functionality. In a first part of this review
      article, we summarize the current knowledge concerning cell junctions and their
      roles in hepatic (patho)physiology. In a second part, we discuss their relevance
      in liver-based in vitro modeling, thereby highlighting the use of primary
      hepatocyte cultures as suitable in vitro models for preclinical pharmaco
      toxicological testing. We further describe the actual strategies to regain and
      maintain cell junctions in these in vitro systems over the long-term.

PMID- 16809102
TI  - Methyl tertiary-butyl ether: studies for potential human health hazards.
AB  - When methyl tertiary-butyl ether (MTBE) in gasoline was first introduced to
      reduce vehicle exhaust emissions and comply with the Clean Air Act, in the United
      States, a pattern of complaints emerged characterised by seven "key symptoms."
      Later, carefully controlled volunteer studies did not confirm the existence of
      the specific key symptoms, although one study of self-reported sensitive (SRS)
      people did suggest that a threshold at about 11-15% MTBE in gasoline may exist
      for SRSs in total symptom scores. Neurobehavioral and psychophysiological studies
      on volunteers, including SRSs, found no adverse responses associated with MTBE at
      likely exposure levels. MTBE is well and rapidly absorbed following oral and
      inhalation exposures. Cmax values for MTBE are achieved almost immediately after
      oral dosing and within 2 h of continuous inhalation. It is rapidly eliminated,
      either by exhalation as unchanged MTBE or by urinary excretion of its less
      volatile metabolites. Metabolism is more rapid humans than in rats, for both MTBE
      and tert-butyl alcohol (TBA), its more persistent primary metabolite. The other
      primary metabolite, formaldehyde, is detoxified at a rate very much greater than
      its formation from MTBE. MTBE has no specific effects on reproduction or
      development, or on genetic material. Neurological effects were observed only at
      very high concentrations. In carcinogenicity studies of MTBE, TBA, and methanol
      (included as an endogenous precursor of formaldehyde, without the presence of
      TBA), some increases in tumor incidence have been observed, but consistency of
      outcome was lacking and even some degree of replication was observed in only
      three cases, none of which had human relevance: alpha(2u)-globulin nephropathy
      related renal tubule cell adenoma in male rats; Leydig-cell adenoma in male rats,
      but not in mice, which provide the better model of the human disease; and B-cell
      derived lymphoma/leukemia of doubtful pathogenesis that arose mainly in lungs of
      orally dosed female rats. In addition, hepatocellular adenomas were significantly
      higher in female CD-1 mice and thyroid follicular-cell adenomas were increased in
      female B6C3F1 mice treated with TBA, but these results lack any independent
      confirmation, which would have been possible from a number of other studies.

PMID- 16809103
TI  - Lead and immune function.
AB  - The heavy metal lead is a widely deposited environmental toxicant known to impact
      numerous physiological systems, including the reproductive, neurological,
      hepatic, renal, and immune systems. Studies illustrating the capacity of lead to
      impair immune function and/or host resistance to disease date back to at least
      the 1960s. However, it has only been in recent years that lead has been
      recognized among a new category of immunotoxicants-those that dramatically shift
      immune functional capacity while producing only modest changes to immune cell
      populations and lymphoid organs. These relatively noncytotoxic immunomodulating
      chemicals and drugs represent the immunotoxic hazards most difficult to identify
      and problematic for risk assessment using historic approaches. As a result, such
      environmental factors are also among the most likely to contribute to chronic
      immune-related disease at relevant exposure levels. This review considers the
      animal and human evidence that lead exposure can produce a stark shift in immune
      functional capacity with a skewing predicted to elevate the risk of atopic and
      certain autoimmune diseases. At the same time, host defenses against infectious
      agents and cancer may be reduced. Age-based exposure studies also suggest that
      levels of blood lead previously thought to be safe, that is, below 10 microg/dl,
      may be associated with later life immune alterations.

PMID- 16809104
TI  - Association of unmet needs for support services with medication use and adherence
      among HIV-infected individuals in the southeastern United States.
AB  - Unmet needs for services, such as housing and psychiatric treatment, are
      relatively common among HIV-infected individuals; however, the effects of
      different types of unmet needs on health-care outcomes are not well understood.
      This study describes unmet psychosocial needs and their relationship with health
      care outcomes among individuals receiving HIV care in the southeastern US
      (n=526). We used multivariate logistic regression to examine the association of
      seven categories of unmet needs with HIV medication use and adherence. Most
      participants (84.5%) reported at least one service need in the past year. Nearly
      half (47%) of participants with service needs reported that at least one need was
      not met. Participants with one or more unmet needs were less likely to be taking
      any HIV medications (p = 0.007) and reported poorer medication adherence
      (p=0.013). The specific unmet needs for benefits (including Social Security,
      health insurance and prescription coverage) (p = 0.006) and a support group
      (p=0.040) were associated with being less likely to be taking any HIV
      medications. Unmet need for mental health-related counseling was associated with
      poorer medication adherence (p=0.003). Study findings regarding the high level of
      unmet need and the association of unmet need with poorer outcomes illustrate the
      importance of interventions to address these needs.

PMID- 16809105
TI  - Support group participation among persons with HIV: demographic characteristics
      and perceived barriers.
AB  - Support groups are widely available for persons living with HIV and some evidence
      supports their efficacy. However, limited information exists regarding
      characteristics of those who utilize HIV support groups. The present study
      examined demographic characteristics and perceived barriers of attenders and non
      attenders of HIV support groups via a mail survey. The 35 respondents were
      predominantly white (71.4%), male (65.7%), homosexual/bisexual (57.1%) and
      diagnosed with HIV within the last five years (62.8%). Results suggested that HIV
      support group attenders had higher educational attainment and a longer time since
      diagnosis than non-attenders. Respondents who expressed interest in HIV support
      group participation were diagnosed more recently than those who did not express
      interest. Respondents who had attended other types of support groups reported
      fewer perceived barriers to participation in HIV support groups. Overall,
      findings suggest that the perception of barriers may be related to interest and
      participation in support groups for HIV and other problems.

PMID- 16809106
TI  - Predictors of post-release primary care utilization among HIV-positive prison
      inmates: a pilot study.
AB  - The primary aims of this exploratory pilot study were (1) to determine the
      proportion of a sample of HIV-positive inmates utilizing primary care after
      recent release, and (2) to identify variables associated with utilization of
      primary care at the time of a post-release interview. Sixty HIV-positive, male
      and female state prison inmates were interviewed approximately three months prior
      to release, and 30 were interviewed again between seven and 21 days after
      release. Variables associated with having utilized primary care at the time of a
      post-release interview (chi(2) p-values < 0.20) included: taking anti-HIV
      medications at the time of release, no alcohol use since release, living in the
      same place as before incarceration and rating of housing situation as
      'comfortable' or 'very comfortable'. For exploratory purposes, these variables
      were entered into a logistic regression model. The model correctly classified 80%
      of cases overall. Future studies are required to ascertain whether these results
      would obtain with a statistically adequate sample size.

PMID- 16809107
TI  - Guardianship of orphans and vulnerable children. A survey of current and
      prospective South African caregivers.
AB  - Increasing numbers of orphaned and vulnerable children resulting from AIDS deaths
      requires practical placement strategies. While the extended family is regarded as
      both the most likely and the preferred option by most key planners and
      organizations, warnings of the limitations of this alternative have been
      increasing. This study assessed the views of 1400 adults (both current and
      prospective caregivers) regarding the placement of children. Most current
      caregivers believed that either their partner (30%), a grandparent (25%) or
      another family member (33%) would look after the child/children if they were no
      longer able to. However, 12% of parents could not identify a carer or predicted
      only a bleak future for their children. There was strong willingness amongst
      adults of various relational proximity to take in children if required to -71% of
      both fathers and grandparents, 63% of siblings and 23% of best friends said they
      would take in children. Nonetheless this research suggests that the willingness
      may not necessarily be translated into reality. Most prospective caregivers
      identified significant additional stressors (most importantly financial) and
      expressed a strong need for assistance if they were to take in additional
      children. The HIV status of the child is also likely to sway placement decisions
      for some people. Nonetheless opportunities to keep children in families are
      clearly high, but people will need considerable help to realize this potential.
      For some children alternatives other than the extended family will be required.

PMID- 16809108
TI  - Rationale and design of the MEMA kwa Vijana adolescent sexual and reproductive
      health intervention in Mwanza Region, Tanzania.
AB  - Large-scale innovative, integrated, multifaceted adolescent sexual and
      reproductive health (ASRH) interventions are urgently needed in sub-Saharan
      Africa. Implementation through schools and health facilities may maximize
      intervention coverage and sustainability, however the impact of the use of these
      structures on intervention content and delivery is not well documented. This
      paper describes the rationale and design of a large-scale multifaceted ASRH
      intervention, which was developed and evaluated over three years in rural
      communities in Mwanza Region, North West Tanzania. The intervention comprised
      community mobilization, participatory reproductive health education in primary
      schools, youth-friendly reproductive health services and community-based condom
      provision for youth. We examine the effect of socioeconomic, cultural and
      infrastructural factors on intervention content and implementation. This paper
      demonstrates the means by which such interventions can be feasibly and
      sustainably implemented to a high standard through existing government health and
      school structures. However, the use of these structures involves compromise on
      some key aspects of intervention design and requires the development of
      complementary strategies to access out-of-school youth and the wider community.

PMID- 16809109
TI  - The gender ratio imbalance and its relationship to risk of HIV/AIDS among African
      American women at historically black colleges and universities.
AB  - African American women are at increased risk of HIV transmission through
      heterosexual contact. HIV/AIDS is the leading cause of death among African
      American women between 25 to 34 years of age, and many of these women were likely
      infected while in college. Four focus groups were conducted with African American
      students attending Historically Black Colleges and Universities (HBCUs) in order
      to learn about the college dating environment and how it influenced women's risk
      of HIV infection. We used constant comparison techniques and visual display
      matrixes to analyse the data. Students identified the gender ratio imbalance of
      more women to men on campus as a key element of the campus dating environment and
      described how it places women at an increased risk for HIV infection. Primary
      consequences of this gender ratio imbalance were men having multiple female
      sexual partners during the same time period and women complying with men's condom
      use preferences. HIV preventive intervention programmes at HBCUs must address the
      gender ratio imbalance and its consequences to reduce women's risk of contracting
      the infection.

PMID- 16809110
TI  - Community outreach with weekly delivery of anti-retroviral drugs compared to
      cognitive-behavioural health care team-based approach to improve adherence among
      indigent women newly starting HAART.
AB  - Sustained virological suppression requires adherence to >95% of doses of therapy.
      Overall there is paucity of data on adherence interventions among women and post
      intervention outcomes. In this pilot study, we evaluated a novel strategy of
      weekly delivery of medications (Directly Delivered Therapy: DDT) for six months
      using an outreach worker (ORW), among ARV naive indigent women starting HAART and
      compared the 'during intervention' and 'post-intervention' outcomes to the health
      care team (a nurse educator, a case worker, a pharmacist and social worker/drug
      addictions counsellor) based approach termed Adherence Coordination Services
      (ACS) and the Standard of Care (SoC) historical referent group. The baseline
      characteristics of the three groups were comparable. The proportion of women who
      achieved sustained virologic suppression in 4-8 month period for DDT; ACS and SoC
      groups were 86% (18/21); 54% (6/11); and 36% (8/22) (P<0.004); and in the 10-14
      month period were 80% (12/15); 54% (6/11) and 45%(10/22) (P=0.036 for DDT vs.
      SoC). Retention rate in the DDT was 87%, and 92% of 307 ORW visits were kept, and
      post-intervention satisfaction was high. Short-term weekly delivery of
      medications using a community based liaison is a feasible, acceptable and a cost
      effective strategy for improving both short-term and perhaps long-term adherence
      among women initiating their first HAART regimen.

PMID- 16809111
TI  - Male and female rural probationers: HIV risk behaviors and knowledge.
AB  - Individuals involved in the criminal justice system are at substantial risk for
      HIV infection and have elevated rates of AIDS. Offenders under community
      supervision, such as probationers, have substantially more opportunities to
      engage in high-risk behaviors than prisoners. Furthermore, probationers in rural
      areas are at risk because rural areas may be slower to adopt HIV risk-reduction
      approaches. Consequently, the primary goal of this study is to describe the HIV
      risk behaviors and level of HIV knowledge of 800 rural felony probationers.
      Bivariate results indicate that males have substantially greater criminal
      histories and engage in more substance use risk behaviors than females. Overall,
      there was minimal and inconsistent use of condoms, but there were no significant
      differences by gender. Gender differences prevailed in perceived HIV knowledge,
      with females reporting high levels of perceived HIV knowledge. Multivariate
      models did not support the hypothesis that perceived knowledge would be a more
      robust correlate of scores on the HIV Risk Behavior Knowledge Test for males than
      females. Results suggest that rural residents are not protected from engaging in
      HIV risk behaviors and future studies should examine gender discrepancies between
      perceived and actual HIV knowledge among offenders under community supervision.

PMID- 16809112
TI  - HIV prevention case management in San Francisco: barriers to successful
      implementation.
AB  - Prevention case management (PCM) is the most labor-intensive HIV prevention
      intervention for persons at risk for acquiring or transmitting HIV. However, it
      has not been thoroughly evaluated. We abstracted client charts (n = 290) from 12
      San Francisco PCM programs and interviewed current and former program directors
      (n=16), case managers (n = 17) and contract managers (n = 4) regarding client
      characteristics, services delivered, barriers to care, cost and organizational
      structure, policies and procedures. Most agencies lacked protocols and data
      collection forms, had high staff turnover, inadequate staff training and
      supervision, experienced difficulty recruiting and retaining clients and could
      not implement PCM guidelines. Half the clients lacked behavioral risk assessment,
      39% were low or no risk, a third received HIV prevention education and a third
      received referrals. Including time spent directly with clients and working on
      their behalf, PCM cost almost four-fold more per client contact than the next
      most costly individual level prevention intervention. Local PCM guidelines,
      reimbursement ties to providing and documenting services and increased
      collaboration between the health department and agencies has greatly improved the
      situation. Outcome evaluations and cost-effectiveness assessments comparing PCM
      to less costly prevention interventions are needed.

PMID- 16809113
TI  - Effect of an armed conflict on human resources and health systems in Cote
      d'Ivoire: prevention of and care for people with HIV/AIDS.
AB  - In September 2002, an armed conflict erupted in Cote d'Ivoire which has since
      divided the country in the government-held south and the remaining territory
      controlled by the 'Forces Armees des Forces Nouvelles' (FAFN). There is concern
      that conflict-related population movements, breakdown of health systems and food
      insecurity could significantly increase the incidence of HIV infections and other
      sexually-transmitted infections, and hence jeopardize the country's ability to
      cope with the HIV/AIDS epidemic. Our objective was to assess and quantify the
      effect this conflict had on human resources and health systems that provide the
      backbone for prevention, treatment and care associated with HIV/AIDS. We obtained
      data through a questionnaire survey targeted at key informants in 24 urban
      settings in central, north and west Cote d'Ivoire and reviewed relevant Ministry
      of Health (MoH) records. We found significant reductions of health staff in the
      public and private sector along with a collapse of the health system and other
      public infrastructures, interruption of condom distribution and lack of
      antiretrovirals. On the other hand, there was a significant increase of non
      governmental organizations (NGOs), some of which claim a partial involvement in
      the combat with HIV/AIDS. The analysis shows the need that these NGOs, in concert
      with regional and international organizations and United Nations agencies, carry
      forward HIV/AIDS prevention and care efforts, which ought to be continued through
      the post-conflict stage and then expanded to comprehensive preventive care,
      particularly antiretroviral treatment.

PMID- 16809114
TI  - Trends in HIV-related morbidity among patients admitted to a South Indian
      tertiary hospital between 1997 and 2003.
AB  - This paper describes trends in HIV-related morbidity among people living with
      HIV/AIDS (PLWHA) admitted to a tertiary hospital in Chennai, South India, between
      1997 and 2003. Patients comprised HIV-infected men, women and children who had
      been admitted at least once to YR Gaitonde Centre for AIDS Research and Education
      (YRGCARE). A non-parametric trends analysis was conducted to observe trends in
      clinical and demographic parameters and diagnoses at admission over the seven
      year period. Among clinical and demographic parameters, we identified a
      significantly increasing time trend in the use of antiretroviral therapy
      (p<0.001) and a significant decrease in the mean hemoglobin level (p=0.01). Among
      diagnoses at admission, we identified a decreasing time trend for admissions due
      to pulmonary tuberculosis (p<0.001) and increasing trends for admissions due to
      extra pulmonary tuberculosis (p<0.01), toxoplasmosis (p<0.01), Pneumocystis
      carinii pneumonia (p=0.02) and anemia (p<0.001). The results indicate a changing
      pattern among the clinical conditions requiring admission. With increasing
      proportions of patients initiating highly active antiretroviral therapy (HAART),
      it is probable that adverse events due to HAART will account for larger
      proportions of admissions in the years to come, as is being seen in the
      industrialized countries.

PMID- 16809115
TI  - Health trends among drug users attending needle exchange programmes in
      Switzerland (1994-2000).
AB  - As a part of an assessment of the Swiss drug harm-reduction policy, cross
      sectional surveys were conducted in 1994, 1996 and 2000 among attenders of all
      needle exchange programmes (NEP) in Switzerland to assess changes in specific
      aspects of their health related to drug use. Data were gathered in each NEP over
      one week, using a questionnaire completed partly with an interviewer and partly
      self administered. The questionnaire covered socio-demographic characteristics,
      drug consumption, risk, prevention behaviour and state of health. Over a 6-year
      period (1994-2000), the average age of NEP attenders rose by 4 years. The
      prevalence of reported HIV remained fairly stable at around 10%. Reported level
      of Hepatitis C prevalence was high (59%). Incidence of used injection equipment
      sharing during the last 6 months was low and stable (9% in 1994, 12% in 2000);
      however, other forms of risk behaviour linked to intravenous drug use, such as
      sharing spoons, cotton or water, were more frequently reported. The HIV epidemic
      among NEP attenders seems to be contained, but this is not the case with
      Hepatitis C, and more attention should be paid to its prevention.

PMID- 16809116
TI  - Access to gynecological services and Papanicolau tests in HIV-infected Italian
      women: a questionnaire survey.
AB  - The objective of the study was to evaluate the access to Papanicolau (Pap) tests
      of HIV-infected women in Italy. A cross-sectional survey on a cohort of HIV
      infected women seen at 27 HIV clinics was performed. At each clinic a female
      physician involved in the care of HIV-infected women was asked questions on
      clinic and patients' characteristics and on access to Pap tests. The outcome of
      the study was to find the percentage of women who had not had a Pap test before
      coming to the HIV clinic and the percentage having had a Pap test in 2001. In the
      survey, 7,600 HIV-infected women were represented. Women who came to the clinic
      without having ever had a Pap test were 62+/-22%, while women who had had a Pap
      test in 2001 were 43+/-36%. Women who reported never having had a Pap test before
      coming to the HIV clinic were more often from the south than the north of Italy
      (17.9+/-49% from the north, 18+/-53% from the center and 9.3+/-83.9% from the
      south; p<0.001). This a difference disappeared when comparing the women who had
      had a Pap test in 2001 (28+/-39.6% from the north, 31.6+/-44.2% from the center
      and 25.6+/-45.7% from the south; p=0.88). Despite the published guidelines in
      Italy, only 38% of women had ever had a Pap test before coming to the HIV clinic
      and only 43% had had a Pap test in 2001. Strategies aimed to improve these
      proportions should be rapidly implemented at all levels of care organization.

PMID- 16809117
TI  - The epidemiology of HIV-1 infection in northern Tanzania: results from a
      community-based study.
AB  - We conducted a community-based study to determine the predictors of HIV-1 among
      women aged 20-44 years (N = 1,418) and their regular male partners (N = 566) from
      randomly selected households in Moshi, Tanzania. The weighted prevalence of HIV-1
      was 10.3% in women and 7% in men. The highest risk of HIV-1 was in subjects whose
      partners were HIV-1 seropositive in both women (adjusted odds ratio (AOR) =
      26.63; 95% confidence interval (CI): 10.74-66.02) and men (AOR = 22.25; 95%CI:
      7.06-70.15). Herpes simplex virus type 2 (HSV-2) and Mycoplasma genitalium were
      also significantly associated with HIV-1. Women with male partners >or=12 years
      older than themselves had increased risk of HIV-1 (AOR = 1.99; 95%CI: 1.01-7.85).
      Other predictors of HIV-1 were history of infertility and the number of sex
      partners in the last three years in women and the age at time of circumcision and
      history of past sexually transmitted diseases (STDs) in male partners. These
      findings show that HIV-1/STDs were major public health problems among women and
      their long-term partners in this population. HIV-1 prevention efforts should
      include promotion of couple's HIV-1 counseling and testing services, control of
      HSV-2, promotion of safer sexual practices and strategies to reduce the age
      difference between women and their partners.

PMID- 16809118
TI  - Factors associated with teachers' implementation of HIV/AIDS education in
      secondary schools in Cape Town, South Africa.
AB  - This study investigated the factors influencing whether high school teachers
      implemented HIV/AIDS education. The independent variables included constructs
      derived from expectancy value theories, teachers' generic dispositions, their
      training experience, characteristics of their interactive context and the school
      climate. We conducted a postal survey of 579 teachers responsible for AIDS
      education in all 193 public high schools in Cape Town. Questionnaires were
      completed and returned by 324 teachers (56% response rate) from 125 schools. Many
      teachers (222; 70%) had implemented HIV/AIDS education during 2003, and female
      teachers were more likely to have implemented than males (74% vs. 58%). The
      teacher characteristics associated with teaching HIV/AIDS were previous training,
      self-efficacy, student-centeredness, beliefs about controllability and the
      outcome of HIV/AIDS education, and their responsibility. The existence of a
      school HIV/AIDS policy, a climate of equity and fairness, and good school
      community relations were the school characteristics associated with teaching
      HIV/AIDS. These findings demonstrate the value of teacher training and school
      policy formulation. They also demonstrate the value and importance of
      interventions that go beyond a sexual health agenda, focussing on broader school
      development to improve school functioning and school climate.

PMID- 16809119
TI  - Mayisha II: pilot of a community-based survey of sexual attitudes and lifestyles
      and anonymous HIV testing within African communities in London.
AB  - The pilot aim was to assess the feasibility and acceptability of undertaking
      anonymous HIV testing using oral fluid samples as part of a community-based
      survey of sexual attitudes and lifestyles of black African communities in London.
      The three components of the study were administered in various venues across
      London: (1) a cross-sectional self-completion anonymous questionnaire survey, (2)
      an optional oral fluid sample for anonymous HIV testing and (3) a nested in-depth
      interview study in a sub-set of respondents. A total of 114 black African men and
      women were recruited. A large number of African countries were represented among
      respondents from newly-migrant and well-established communities. The response
      rate to the oral fluid sample was high at 82% and all samples collected were of
      sufficient quality to be tested for HIV. In-depth interviews with respondents
      revealed positive views and experiences about participating in the study whilst
      understanding of the questionnaire was good. We therefore conclude that anonymous
      HIV testing as part of a community-based survey is feasible and acceptable,
      whilst a set of recommendations was produced to refine the survey methodology and
      questionnaire. Participatory research methods are essential for achieving
      successful community-based surveys among black Africans in Britain.

PMID- 16809121
TI  - Baseline predictors of three types of antiretroviral therapy (ART) adherence: A 2
      year follow-up.
AB  - The purposes of the study were to measure adherence with antiretroviral therapy
      to dose, schedule, and dietary instructions in a sample of patients with HIV
      infection in Stockholm, Sweden, over a 2-year period and identify baseline
      predictors of the three types of adherence. The study cohort consists of 144
      patients who completed at least six out of seven follow-up self-reported
      adherence questionnaires. Baseline self-administrated questionnaire examined
      socio-demographics, medication-related, psychological, cognitive, and social
      context factors and self-reported adherence. Biomedical data were obtained
      through patients' medical records. Summary dose, schedule, and dietary
      instructions adherence scores provided outcome measures reflecting 100% adherence
      across all time points or not 100% adherence during at least one measurement
      period. A total of 61% maintained consistent full-dose adherence throughout
      baseline and all follow-up visits and equivalent proportion of 100% schedule
      adherence was 39%. Among patients with dietary instructions, 37% retained
      consistent adherence at all visits. Only schedule adherence was predicted by
      baseline data; perceived pressures from medical staff to take HIV medications (OR
      0.51, p < .05), life stress (OR 0.13, p < .01), ART health concerns (OR 0.19, p <
      .01), and ART prolongs one's life (OR 0.39, p < .05) predicted reduced schedule
      adherence over time. Perceived medication pressures from those close to the
      patient (OR 1.76, p < .05), post-traumatic stress disorder symptoms (OR 1.07
      p<.01), and adherence self-efficacy (OR 3.50, p < .05) predicted positive
      schedule adherence over time. These results clearly illustrate difficulties in
      sustaining ART adherent behaviour, in particular schedule and dietary
      restrictions, over time and thus emphasizes the importance of multiple periodic
      assessments of all three types of adherence. Interventions aimed at improving
      schedule adherence should in particular focus on psychological and cognitive
      factors.

PMID- 16809123
TI  - Disease categories and disease kinships: classification practices in the U.S.
      environmental breast cancer movement.
AB  - U.S. breast cancer activists have increasingly focused their efforts on
      addressing environmental causes of the disease. These efforts have included
      raising public awareness about environmental risks, pushing for scientific
      research on environmental causes, and promoting more stringent environmental
      regulations. As part of this work, activists have consistently "classified"
      breast cancer within broader disease categories that shape how activists
      conceptualize and carry out their political agendas. In this paper I explore the
      role that three disease categories--women's health, cancer, and endocrine
      disruption--have played in the U.S. environmental breast cancer movement. In
      doing so, I also show how activists' classification practices are simultaneously
      "disease kinship" practices that are just as integral to the movement's efforts
      as are the disease categories to which they are bound. By examining the
      centrality of diseases classification and disease kinship practices to
      environmental breast cancer activism, my account demonstrates the potential
      benefits of conducting similar analyses of other health-based social movements.

PMID- 16809124
TI  - The social life of genetic knowledge: a case-study of choices and dilemmas in
      cancer genetic counselling in Denmark.
AB  - This article explores the social life of genetic knowledge in the context of
      cancer genetic counselling in Denmark. I focus on a specific case that occurred
      during my study of the processes through which genetic risk profiles are produced
      and through which knowledge of genes and kinship comes to appear both meaningful
      and contestable to counsellees. The analysis illuminates how participants in
      cancer genetic counselling experience gaps between, on the one hand, genetic
      information about kinship and predispositions to hereditary disease and, on the
      other hand, social experiences of kinship and risks. I argue that this gap
      constitutes a space for agency in which people make their own connections and
      interpretations. It is in this space that new social relations and understandings
      of bodies, health and kinship are crafted. Following the social life of genetic
      knowledge highlights how knowledge is practiced through social relations and how
      knowing is grounded in particular interactions and situated concerns.

PMID- 16809125
TI  - Dark Winter and the spring of 1972: deflecting the social lessons of smallpox.
AB  - This article examines how the master status of bioterrorism has distracted
      professional and political attention from the social lessons of smallpox. I
      illustrate this by comparing an influential bioterrorism simulation known as Dark
      Winter with the social history surrounding the Yugoslavian smallpox epidemic of
      1972. Dark Winter's epidemiological premises were largely based upon what was
      learned from the Yugoslavian outbreak. Yet, although this epidemic was non
      deliberate, the exercise did not attend to the social conditions within which it
      developed. Most notably, it did not consider that this epidemic was mainly borne
      by marginalized communities of Kosovan Albanians and that difficulties in
      controlling it were linked to the relative lack of pre-existing public health
      infrastructure among these people; instead, the Dark Winter exercise mainly
      focused upon the proximate determinants of violence and its immediate management.
      This distraction from the social dynamics of infectious diseases has major
      implications for the prevention and management of future outbreaks, regardless of
      whether or not they are deliberately initiated.

PMID- 16809126
TI  - Simultaneous valve replacement and venous patch repair of superior mesenteric
      artery aneurysm due to infective endocarditis: a case report.
AB  - BACKGROUND: Peripheral mycotic aneurysm development is a rare systemic
      complication of infective endocarditis. CASE REPORT: We report on a case of a
      mycotic aneurysm of the superior mesenteric artery in a 66-year-old man with
      infective endocarditis of the mitral valve. After the mitral valve was replaced
      by a mechanical valve, a laparotomy was performed. The mycotic aneurysm was
      excised and the vessel was repaired by sewing an autologous venous patch at the
      neck of the aneurysm. Five years after the operation, the patient is doing fine,
      with a normal morphology and patency of the superior mesenteric artery.
      CONCLUSION: Our case demonstrates that simultaneous valve surgery and repair of a
      superior mesenteric artery mycotic aneurysm by sewing a vein patch in the neck of
      the artery is a viable treatment option.

PMID- 16809127
TI  - Direct left ventricle-to-coronary artery stent restores perfusion to chronic
      ischemic swine myocardium.
AB  - BACKGROUND: Direct left ventricle (LV)-to-coronary artery shunts (VSTENT) have
      been proposed as an alternative means of myocardial revascularization. The goal
      of this study was to examine quantitative changes in myocardial perfusion and
      possible mechanisms of revascularization with an LV-to-coronary shunt. METHODS:
      Ameroid occluders were implanted on the proximal left anterior descending
      coronary artery (LAD) of 6 pigs to create chronic ischemia. Four weeks later, a
      VSTENT was placed to directly connect the distal LAD with the LV chamber. Animals
      survived for an additional 3 weeks and received periodic bromodeoxyuridine (BrdU)
      injections to identify dividing cells to identify and quantify angiogenesis.
      Regional myocardial perfusion (RMP) was measured with color microspheres under
      adenosine vasodilatory stress before and 3 weeks after VSTENT implantation.
      Vascularity was assessed histologically by an overall vascularity index and a
      growth index reflecting the density of BrdU-positive vascular cells. RESULTS:
      Three weeks after VSTENT placement, RMP improved from 38.4% +/- 19.6% of non
      ischemic flow to 86.8% +/- 13.7% in treated animals (P < .05). This benefit was
      accompanied by histological evidence of increased vascularity and vascular
      proliferation. Four of 5 animals had patent and functional devices at the end of
      the study. CONCLUSION: Chronic VSTENT placement improves RMP and may promote
      arterial remodeling in chronically ischemic porcine myocardium.

PMID- 16809128
TI  - Topical application of bacitracin ointment is associated with decreased risk of
      mediastinitis after median sternotomy.
AB  - BACKGROUND: The diagnosis of mediastinitis after open-heart surgery is infrequent
      but dreaded as it carries a high morbidity and mortality. The purpose of this
      study was to investigate the impact that topical antibacterials would have on the
      postoperative mediastinitis rate. METHODS: Data were collected from 2455
      consecutive patients who underwent sternotomy and cardiopulmonary bypass for both
      valvar and ischemic heart disease. Prior to 1999, patients (n = 1036) underwent
      surgery with standard perioperative intravenous antibiotics but no application of
      bacitracin. After 1999, patients (n = 1419) underwent surgery with intravenous
      antibiotics and application of bacitracin ointment to the sternotomy incision
      after closure. RESULTS: Cases of mediastinitis occurred in 12 patients (1.2%) not
      treated with bacitracin, which required re-exploration, sternectomy, and soft
      tissue closure of the mediastinum. Alternatively, 3 patients (0.2%) in the group
      treated with bacitracin developed mediastinitis (P < .01). Therefore, the use of
      topical antibacterials was associated with a 6-fold reduction in the risk of
      mediastinitis after cardiac surgery. This significant difference in the infection
      rate was observed even though the percentage of patients with risk factors for
      mediastinitis was equal to greater than the group not treated with bacitracin.
      Non-bacitracin versus bacitracin: diabetics, 298 versus 484; emergency
      operations, 24 versus 50; bilateral internal thoracic grafts, 28 versus 29; and
      obesity (body mass index >30), 294 versus 396. CONCLUSIONS: The use of topical
      antibacterials is associated with a decrease in the risk of mediastinitis after
      cardiac surgery.

PMID- 16809129
TI  - Evaluation of ascending aortic atherosclerosis with 16-multidetector computed
      tomography is useful before total endoscopic coronary bypass surgery.
AB  - BACKGROUND: The purpose of this study was to investigate the assessment of
      ascending aortic atherosclerosis with 16-multidetector computed tomography (16
      MDCT) angiography prior to total endoscopic coronary artery bypass (TECAB)
      surgery. METHODS: Forty-five patients were examined with electrocardiogram-gated,
      16-MDCT angiography. The presence of atherosclerosis at the ascending aorta was
      graduated as severe (>50% of circumference) or as mild (<50% of circumference).
      Ascending aortic plaque composition was evaluated based on CT densities expressed
      as Hounsfield units (HU). TECABs using the Da Vinci telemanipulator were
      performed either on the arrested heart (n = 39) with an intra-aortic
      cardiopulmonary bypass (CPB) perfusion device or on the beating heart (n = 6) in
      patients with severe atherosclerosis. RESULTS: The presence of mild
      atherosclerosis at the ascending aorta (11/39) was associated with intra-aortic
      CPB perfusion device-related difficulties such as intra-aortic balloon migration
      (BM) or balloon rupture (P = .007) in arrested heart TECABs. The CT density of
      atherosclerotic plaque in patients with BM was mean 58 HU +/- 51 standard
      deviation (SD), suggesting noncalcifying plaque. In patients without BM, CT
      density of plaque was mean 526 HU +/- 306 SD corresponding to calcifying plaque
      (P < .001). Balloon rupture occurred in 2 patients who had calcifying plaque at
      the ascending aorta. CONCLUSION: Evaluation of ascending aortic atherosclerosis
      with 16-MDCT angiography is useful prior to TECAB surgery. Even mild
      atherosclerosis of the ascending aorta is associated with intraoperative
      difficulties regarding the remote-access perfusion system that is used for
      arrested heart TECAB surgery.

PMID- 16809130
TI  - Pharmacokinetics of 125I-radiolabelled PEG-hemoglobin SB1.
AB  - PEG-hemoglobin SB1 (SB1) is a polyethylene glycol (PEG)-modified hemoglobin-based
      oxygen carrier, intended for use as resuscitation fluid for brain stroke and as a
      blood substitute. An intravenous pharmacokinetics (PK) studies with SB1 was
      investigated in male albino Sprague-Dawley (SD) rats and male beagle dogs at
      doses of 5 and 12.5 ml/kg for rats and 10 ml/kg for dogs. Total hemoglobin in
      plasma and whole blood was determined by gamma scintillation counter-detecting
      125I-radiolabelled SB1. In the 5 ml/kg rats (n = 9), the Cmax, t1/2, AUCt and
      Tmax were 9.055 mg equivalents/ml, 9.6 hr, 79.6 mg equivalents.hr/ml and 0.20 hr
      in the plasma and 4.954 mg equivalents/ml, 9.7 hr, 37.6 mg equivalents.hr/ml and
      0.11 hr in the whole blood, respectively. Those parameters in the 12.5 ml/Kg of
      rats (n = 9) were 19.00 mg equivalents/ml, 10.6 hr, 223.5 mg equivalents.hr/ml
      and 0.33 hr in the plasma and 10.58 mg equivalents/ml, 16.1 hr, 99.0 mg
      equivalents.hr/ml and 0.33 hr in the whole blood, respectively. An increase in
      the dose level from 5 to 12.5 ml/kg resulted in the increase in both Cmax and
      AUC24, and the increases in these parameters appeared to be in proportion to the
      dose increment. Thus, following the 2.5-fold increase in administered dose, Cmax
      was increased by a factor of 2.1 in both plasma and whole blood, while AUC24 was
      increased by a factor of 2.8 for plasma and 2.6 for whole blood. In the dogs
      receiving 10 ml/kg (n = 3), the Cmax, t1/2, AUC168 and Tmax were 12.70 mg
      equivalents/ml, 47.2 hr, 425.7 mg equivalents.hr/ml and 0.083 hr in the plasma
      and 8.372 mg equivalents/ml, 50.3 hr, 241.3 mg equivalents.hr/ml and 1.003 hr in
      the whole blood, respectively. The present work provides an insight into the
      pharmacological behavior of a PEG-modified hemoglobin.

PMID- 16809131
TI  - Evaluation of RGD modification on collagen matrix.
AB  - OBJECTIVE: To observe the changes during the process of modificating collagen
      with Arg-Gly-Asp (RGD) peptide, a series experiments were designed. METHODS: The
      3D porous collagen matrices modified with RGD peptide were constructed by
      lyophilization. The modified and unmodified matrices were characterized by
      Scanning Electron Microscopy (SEM) and Electron Spectroscopy for Chemical
      Analysis (ESCA). Fibroblasts were used to evaluate the cell compatibility of the
      matrices. RESULTS: In terms of cell growth, the cells attached much better on the
      modified matrix than on the unmodified one. Compare to the unmodified matrices,
      the polar groups on the modified matrix increased. CONCLUSIONS: The introducing
      of specific RGD receptor-mediated adhesion site on matrices obviously enhanced
      the cells adhesion on collagen matrices.

PMID- 16809132
TI  - Comparative analysis of polymer and linker chemistries on the efficacy of
      immunocamouflage of murine leukocytes.
AB  - Membrane grafting of methoxypoly(ethylene glycol) [mPEG] to allogeneic leukocytes
      attenuates allorecognition and significantly reduces the risk of graft-versus
      host disease in mice. To optimize the immunological efficacy of polymer grafting,
      murine splenocytes were modified using three differing linker chemistries: CmPEG
      (5 kDa), BTCmPEG (5 and 20 kDa) and TmPEG (5 kDa). In vitro immunocamouflage
      efficacy was examined by flow cytometic analysis of leukocyte markers and mixed
      lymphocyte reactions (MLR). In contrast to CmPEG and BTCmPEG, TmPEG exerted
      significant cellular toxicity. Flow cytometric analysis demonstrated that both
      CmPEG and BTCmPEG were highly effective at camouflaging cell surface markers
      while TmPEG was ineffective. Furthermore, CmPEG and BTCmPEG dramatically blocked
      MLR allorecognition and cellular proliferation. Polymer length was the most
      critical factor in the immunocamouflage of cells with the BTCmPEG 20 kDa being
      the most effective. In contrast to other immunomodulatory approaches,
      immunocamouflage of leukocytes yields a multivalent effect globally interfering
      with attachment, allorecognition, presentation and costimulation pathways.

PMID- 16809133
TI  - Preparation and properties of thermoresponsive bioconjugates of trypsin.
AB  - Covalent attachment of enzymes and other proteins to the smart polymer, poly(N
      isopropylacrylamide) [poly (NIPAAm)], has been widely used as a method for the
      preparation of thermosensitive protein conjugates. In the present study,
      reversible soluble-insoluble polymer-enzyme conjugates were prepared by
      conjugating a copolymer of NIPAAm with 5-mol % of 6-acrylaminohexanoic acid to
      trypsin by the carbodiimide-NHS (N-hydroxysuccinimide) coupling method. Four
      bioconjugates with different units of enzyme coupled to the matrix were prepared.
      Increased enzymatic activity in terms of high effectiveness factor (in the range
      of 3-5) was found in the conjugates. Kinetic parameters for the immobilized and
      free enzyme were determined. The Vmax/Km value of the enzyme significantly
      increased on immobilization by the factors in the range of 12-28. The immobilized
      enzyme also showed stability to autolysis at 50 degrees C.

PMID- 16809134
TI  - Determination of creatine in commercial creatine powder with new potentiometric
      and amperometric biosensors.
AB  - New potentiometric and amperometric biosensors were developed for the
      determination of creatine. The potentiometric creatine biosensor was prepared by
      immobilizing urease and creatinase on poly(vinylchloride) (PVC) ammonium membrane
      electrode containing palmitic acid prepared by using nonactine as an ammonium
      ionophore. The linear working range of the biosensor was 1.0 x 10(-5) - 1.0 x 10(
      3) M and the response time was about 60 s. The optimum pH, temperature, and
      buffer concentration were found to be 7.0, 20 degrees C, and 5 mM, respectively.
      The slope of the electrode was 49.2 mV/p[creatine]. The storage stabilization of
      the biosensor was investigated and 40-45% decrease in the response was detected
      after 2 months. The amperometric creatine biosensor was prepared by immobilizing
      creatinase (CI) and sarcosine oxidase (SO) in a poly(vinylferrocenium) matrix
      onto the surface of a platinum working electrode by crosslinking with
      glutaraldehyde (GA) and bovine serum albumine (BSA). Determination of creatine
      was performed by the oxidation of enzymatically generated H2O2 at +0.7 V vs.
      Ag/AgCl. The linear working range of the biosensor was 2.0 x 10(-5) - 3.2 x 10(
      4) M and the response time was about 50 s. The effects of pH, temperature, enzyme
      ratio and buffer concentration were investigated and optimum parameters were
      found to be 7.5, 37 degrees C, 2.5:1 (CI:SO) and 0.05 M, respectively. The
      determination of creatine in commercial creatine powder was successfully carried
      out with these creatine biosensors by using the standard addition and calibration
      curve methods. The results were in good agreement with those obtained from Jaffe
      method at 95% confidence level.

PMID- 16809135
TI  - Polymethylmethacrylate (PMMA) as an embedding medium preserving tissues and
      foreign materials encroaching in endovascular devices.
AB  - Problems of displacement, poor healing, degradation of the polymers and corrosion
      of the metallic frame in endovascular devices still require in-depth
      investigations. As the tissues and the foreign materials are in close contact, it
      is of paramount importance to efficiently investigate the interfaces between
      them. Inclusion in polymethymethacrylate (PMMA) permits us to obtain thin slides
      and preserve the capacity to perform the appropriate stainings. An AneuRx
      prosthesis was harvested in bloc with the surrounding tissues at the autopsy of a
      patient 25 months post deployment in a 5.7 cm diameter AAA and sectioned in the
      direction of the blood flow in two halves. A cross-section of the encapsulated
      distal segment together with the surrounding aneuryshmal sac was embedded in
      polymethylmethacrylate (PMMA). Further to complete polymerization, slices of the
      specimen were cut on a precision banding saw under coolant. They were affixed
      onto methacrylate slides with a UV cured adhesive. Binding and polishing were
      done on a numeric grinder and slices 25 to 30 microm in thickness were stained
      with toluidine blue prior to observation in light microscopy. Additional slices
      were prepared for scanning electron microscopy and X-ray energy dispersive
      spectrometry for determination of the elemental composition of the Nitinol stent.
      The aortic wall did not demonstrate complete integrity along with its
      circumference. Some areas of rupture were noted. The content of the sac was
      heavily shrunk and was mostly acellular. The walls of the device were very well
      encapsulated. The PMMA embedding permitted the polyester wall, the Nitinol wire
      and the collagen to keep in close contact. Scanning electron microscopy involved
      backscattered electrons and confirmed the corrosion the Nitinol wire at the
      boundary with living tissues. Based upon the results obtained, we believe that
      PMMA embedding is the most appropriate method to process endovascular devices for
      histological and material investigation. Needless to say, that paraffin embedding
      would have not been feasible for such a big size specimen involving different
      materials.

PMID- 16809136
TI  - An amperometric biosensor for uric acid determination prepared from uricase
      immobilized in polypyrrole film.
AB  - In order to prepare a biosensor for the determination of uric acid,
      electropolymerization of pyrrole on Pt surface was carried out with an
      electrochemical cell containing pyrrole, ferrocene (as a electron mediator) and
      tetrabutylammonium tetrafluoroborat in acetonitrile by cyclic voltammetry between
      0.0 and 1.0 V (vs. Ag/AgCl) at a scan rate of 50 mV/s upon Pt electrode. Uricase
      was immobilized by a glutaraldehyde/gelatine croslinking procedure on to
      polypyrrole film after the electropolymerization processes. The response of the
      biosensor against uric acid was measured after 330 seconds following the
      application of a constant potential of +0.7 V (vs. Ag/AgCl). The resulting
      biosensor exhibits excellent electrocatalysis for the uric acid. The amperometric
      determination is based on the electrochemical detection of H2O2, which is
      generated in enzymatic reaction of uric acid. The sensor responds to uric acid
      with a detection limit of 5.0 x 10(-7) M. The sensor remains relatively stable
      for 5 weeks. Interference effect were investigated on the amperometric response
      of the biosensor. Determination of uric acid was carried out in the biological
      fluids by biosensor.

PMID- 16809137
TI  - Camphor Poisoning: an evidence-based practice guideline for out-of-hospital
      management.
AB  - A review of national poison center data from 1990 through 2003 showed
      approximately 10,000 annual ingestion exposures to camphor-containing products. A
      guideline that determines the threshold dose for emergency department referral
      and need for pre-hospital decontamination could potentially avoid unnecessary
      emergency department visits, reduce health care costs, optimize patient outcome,
      and reduce life disruption for patients and caregivers. An evidence-based expert
      consensus process was used to create the guideline. Relevant articles were
      abstracted by a trained physician researcher. The first draft of the guideline
      was created by the primary author. The entire panel discussed and refined the
      guideline before distribution to secondary reviewers for comment. The panel then
      made changes based on the secondary review comments. The objective of this
      guideline is to assist poison center personnel in the appropriate out-of-hospital
      triage and initial management of patients with suspected exposures to camphor
      containing products by 1) describing the manner in which an exposure to camphor
      might be managed, 2) identifying the key decision elements in managing cases of
      camphor exposure, 3) providing clear and practical recommendations that reflect
      the current state of knowledge, and 4) identifying needs for research. This
      guideline applies to camphor exposure alone. Co-ingestion of additional
      substances, such as in commercial products of camphor combined with other
      ingredients, could require different referral and management recommendations
      depending on the combined toxicities of the substances. This guideline is based
      on an assessment of current scientific and clinical information. The expert
      consensus panel recognizes that specific patient care decisions may be at
      variance with this guideline, and are the prerogative of the patient and the
      health professionals providing care, considering all of the circumstances
      involved. This guideline does not substitute for clinical judgment.
      Recommendations are in chronological order of likely clinical use. The grade of
      recommendation is in parentheses. 1) Patients with stated or suspected self-harm
      or who are the recipients of malicious administration of a camphor-containing
      product should be referred to an emergency department immediately, regardless of
      the amount ingested (Grade D). 2) Patients who have ingested more than 30 mg/kg
      of a camphor-containing product or who are exhibiting symptoms of moderate to
      severe toxicity (e.g., convulsions, lethargy, ataxia, severe nausea and vomiting)
      by any route of exposure should be referred to an emergency department for
      observation and treatment (Grade D). 3) Patients exhibiting convulsions following
      a camphor exposure should be transported to an emergency department by pre
      hospital emergency medical care providers (Grade D). A benzodiazepine should be
      used to control convulsions (Grade C). 4) Patients who have been exposed to a
      camphor product and who remain asymptomatic after 4 hours can be safely observed
      at home (Grade C). 5) Induction of emesis with ipecac syrup should not be
      performed in patients who have ingested camphor products (Grade C). 6) Activated
      charcoal administration should not be used for the ingestion of camphor products.
      However, it could be considered if there are other ingredients in the product
      that are effectively adsorbed by activated charcoal or if other substances have
      been co-ingested. (Grade C). 7) For asymptomatic patients with topical exposures
      to camphor products, the skin should be thoroughly washed with soap and water and
      the patient can be observed at home for development of symptoms (Grade C). 8) For
      patients with topical splash exposures of camphor to the eye(s), the eye(s)
      should be irrigated in accordance with usual poison center procedures and that
      referral take place based on the presence and severity of symptoms (Grade D). 9)
      Patients with camphor inhalation exposures should be moved to a fresh air
      environment and referred for medical care based on the presence and severity of
      symptoms. It is unlikely that symptoms will progress once the patient is removed
      from the exposure environment (Grade D).

PMID- 16809138
TI  - Aristolochic acids detected in some raw Chinese medicinal herbs and manufactured
      herbal products--a consequence of inappropriate nomenclature and imprecise
      labelling?
AB  - BACKGROUND: Certain frequently used Chinese herbal medicines commonly used for
      weight control, may contain toxic Aristolochia species, which have been
      associated with severe nephropathy and urothelial cancer in humans and animals.
      The toxic entities in Aristolochia species are aristolochic acid-I (AA-I) and
      aristolochic acid-II (AA-II). There is a lack of systematic information about the
      aristolochic acid content of Aristolochia species and related genera, including
      those in Chinese materia medica that are used in the treatment of overweight
      individuals. OBJECTIVES: To determine the content of AA-I and AA-II of commonly
      used Chinese herbal medicines (raw herbs and manufactured products) including
      species of Aristolochia and related genera. METHODS: Twenty-one raw herbs and
      seven manufactured herbal products were purchased from herbal wholesalers and
      traditional Chinese medicinal herb retailers in Melbourne, Australia in September
      2003, after the supply of known aristolochic acid-containing herbs and products
      had been banned in Australia. Six additional raw herbs were sourced from a herbal
      teaching museum. These were purchased in 2001, before the prohibition. The
      contents of aristolochic acids of each was determined by high pressure liquid
      chromatography (HPLC), and confirmed by liquid chromatography-mass spectrometry
      (LC-MS). RESULTS: Of the samples tested, four of the raw herbs purchased before
      the ban and two manufactured products purchased after the ban, were found to
      contain aristolochic acids (16-1002 ppm). CONCLUSIONS: Several Chinese raw herbs
      and some commercially available manufactured herbal products contain aristolochic
      acids. The confusion in Chinese nomenclature for related raw herbs, and imprecise
      labelling of manufactured products may contribute to the inadvertent use of toxic
      herbal species in Chinese medicine practice. Additional measures are needed to
      ensure the safety of consumers of Chinese herbal medicines.

PMID- 16809139
TI  - "Parachuting" meth: a novel delivery method for methamphetamine and delayed-onset
      toxicity from "body stuffing".
AB  - BACKGROUND: Methamphetamine is an illicit stimulant that is typically smoked,
      insufflated, or injected. We report an unusual method of ingesting
      methamphetamine called "parachuting" and its implications for the treatment of
      "body stuffers." CASE REPORT: A 25-year-old man wrapped methamphetamine into a
      plastic baggie and ingested it in an attempt to "parachute." He presented to an
      Emergency Department 10 hours after his ingestion because he realized that he
      forgot to puncture the baggie. He had no complaints and had a transient
      tachycardia. He was treated with activated charcoal and whole bowel irrigation,
      observed for 24 hours, and discharged. He returned 42 hours after his ingestion
      with tachycardia (220 bpm), agitation, hypertension (179/74 mmHg), and
      rhabdomyolysis (CPK 7771 U/L), requiring mechanical ventilation and a midazolam
      drip (10 mg/hr). CONCLUSION: "Parachuting" is a novel method of ingesting
      methamphetamine. We report a case of a single-packet "body stuffer" with severe
      symptom onset that was delayed over 36 hours. Treatment protocols for "body
      stuffers" using this technique may require more prolonged observation and/or
      imaging studies to determine the absence of gastrointestinal packets.

PMID- 16809140
TI  - Ceftazidime overdose-related nonconvulsive status epilepticus after
      intraperitoneal instillation.
AB  - We report a case of ceftazidime-related nonconvulsive status epilepticus (NCSE)
      in a 70-year-old female patient with continuous ambulatory peritoneal dialysis
      (CAPD)-related peritonitis. She was given ceftazidime intravenously which was
      then changed to intraperitoneal installation after clinical improvement. She
      received 11 g of ceftazidime via intraperitoneal installation for two days after
      being discharged from the hospital. Her consciousness was altered with mutism,
      asterisxis, and horizontal nystagmus. Her EEG showed continuous generalized three
      spikes-and-wave per second that were abolished after intravenous diazepam.
      Ceftazidime-related NCSE was suggested and ceftazidime therapy was stopped.
      Hemodialysis was done while phenytoin was also given to control the convulsions.
      Her consciousness improved after hemodialysis. Serum ceftazidime measured before
      and after hemodialysis on the second and third day were 105.2/39.4, 36.2/5.2
      microg/mL (normal peak level 55 microg/mL), respectively. Repeated evaluation on
      day 6 showed normal EEG without epileptiform activity. She was later discharged
      with full recovery.

PMID- 16809141
TI  - Acute hepatic injury and renal failure after ingestion of snake gallbladder.
AB  - Ingestion of snake gallbladder has been practiced in ancient Chinese
      civilizations to improve vision and relieve arthritic pain. Although little is
      known about the composition of snake gallbladder, ingestion is still practiced in
      some Chinese cultures. Adverse effects of ingesting snake gallbladder have not
      yet been reported. Here, we present a case of acute hepatic injury and delayed
      onset renal failure after ingestion of snake gallbladders. The patient
      subsequently recovered after supportive care, combined with plasma exchange and
      hemodialysis. He was the only survivor of the four victims suffering from
      intoxication of snake gallbladder in the last three years in our hospital.

PMID- 16809142
TI  - Intoxication following minor stabs from the spines of a porcupine fish.
AB  - We report an unusual intoxication by tetrodotoxin (TTX). A curator of an aquarium
      sustained minor punctures in his finger from the spines of a porcupine fish
      during an autopsy of a dead porcupine fish. He developed paresthesias, numbness,
      paresis, dizziness and headache. The death of the fish might have caused some
      autolysis, leading to increased availability of TTX. In combination with direct
      contact with the organ fluids, this probably led to TTX exposure via minor
      wounds.

PMID- 16809143
TI  - Neither DMPS nor DMSA is effective in quantitative elimination of elemental
      mercury after intentional IV injection.
AB  - BACKGROUND: Intravenous injection of elemental mercury (Hg) is rare and
      considered relatively harmless. Treatment recommendations vary and the
      effectiveness of chelation therapy is controversial. CASE REPORT: A 27-year-old
      man intravenously injected 1.5 mL of elemental Hg. Within 12 hours he became
      febrile, tachycardic and dyspneic. Physical examination was unremarkable. X-rays
      showed scattered radiodense deposits in the lung, heart, intestinal wall, liver
      and kidney. The serum Hg level on admission was 172 microg/L and peaked on day 6
      at 274 microg/L. Cumulative renal elimination during a five day oral treatment
      period with 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3
      dimercaptosuccinic acid (DMSA) was 8 mg and 3 mg, respectively. CONCLUSION:
      Although urinary excretion could be enhanced during chelation therapy, Hg
      deposits in organs resulted in negligible elimination of mercury compared to the
      exposed dose.

PMID- 16809144
TI  - Clinical images in medical toxicology: heroin overdose with non-cardiogenic
      pulmonary edema.

PMID- 16809147
TI  - High prevalence of SV40 infection in patients with nodal non-Hodgkin's lymphoma
      but not acute leukemia independent of contaminated polio vaccines in Taiwan.
AB  - Recent studies have linked simian virus 40 (SV40) to non-Hodgkin's lymphoma
      (NHL), especially in countries in which people were exposed to contaminated polio
      vaccines prior to 1963. In Taiwan, nearly all children were not exposed to
      contaminated polio vaccine during this period; the relationship between SV40
      infection and hematological malignancies is unclear and deserves to be studied.
      Using PCR amplification of SV40 large T antigen DNA, confirmed by Southern blot
      hybridization and sequence analysis, 91 frozen lymph nodes from NHL patients were
      examined. Thirteen (14.3 percent) showed positive for SV40. All other test
      samples, including diagnostic bone marrow from patients with acute leukemia,
      peripheral blood from 10 relatives of SV40 positive-patients and 91 age-matched
      normal volunteers, and 5 reactive hyperplastic lymphoid tissues, showed negative.
      These results may reflect that human-to-human transmission of SV40 is independent
      of contaminated polio vaccines; and SV40 is possibly associated with the
      development of NHL in Taiwan (p = 0.0001). Prospective studies are needed to
      determine the prevalence of SV40 infections in our and other human populations
      and to explore the means of transmission of the virus.

PMID- 16809148
TI  - A phase II study of doxorubicin, cisplatin, and 5-fluorouracil in patients with
      advanced adenocarcinoma of the stomach or esophagus.
AB  - BACKGROUND: The combination of epirubicin, cisplatin, and infusional 5
      fluorouracil (ECF) currently represents a standard and effective regimen for the
      treatment of advanced gastroesophageal cancer. The use of doxorubicin as an
      alternative to epirubicin in the ECF regimen has not been evaluated. METHODS:
      Thirty-two patients with metastatic adenocarcinoma of the stomach,
      gastroesophageal junction, or esophagus were treated with cisplatin 60 mg/m2 and
      doxorubicin 30 mg/m2 repeated every 21 days, in combination with infusional 5
      fluorouracil 200 mg/m2/day (ACF). RESULTS: Major objective responses were
      observed in 28 percent of patients (46 percent previously untreated; 13 percent
      previously treated), with one complete response. The median progression-free
      survival was 4.0 months, and the median overall survival was 5.8 months (9.3
      months previously untreated; 4.5 months previously treated). The major (Grade 3
      4) toxicities were neutropenia (34 percent), anorexia (31 percent), nausea (28
      percent), diarrhea (19 percent), and stomatitis (16 percent). CONCLUSION: In
      comparison with historical data taken from published trials of ECF, the ACF
      regimen appears similar in efficacy when differences in prior treatment status
      are taken into account. However, ACF appears to be associated with a higher
      incidence of major toxicities. Our findings therefore support the continued use
      of epirubicin rather than doxorubicin in combination chemotherapy regimens for
      advanced gastroesophageal cancer.

PMID- 16809149
TI  - Thymidylate synthase and dihydropyrimidine dehydrogenase are related to
      histological effects of 5-fluorouracil and cisplatin neoadjuvant chemotherapy for
      primary gastric cancer patients.
AB  - Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and vascular
      endothelial growth factor (VEGF) are associated with the effect of 5-fluorouracil
      (5-FU) based adjuvant chemotherapy. However, very few studies have investigated
      the relationship between these factors and 5-FU neoadjuvant chemotherapy for
      primary gastric cancer patients. In this study, we studied the correlation
      between these markers and the histological chemotherapeutic effect in advanced
      gastric cancer with neoadjuvant chemotherapy. METHODS: Sixty-two primary advanced
      gastric cancer patients were recruited into the study. One cycle of continuous
      infusion of 5-FU (300 mg/m2/day, 14 days) plus drip infusion of cisplatin (15
      mg/m2/day, Day one and Day two) was performed as neoadjuvant chemotherapy.
      Histological chemotherapeutic responses of the resected specimens were classified
      into responders and nonresponders. TS, DPD, VEGF expressions both before and
      after neoadjuvant chemotherapy were examined immunohistochemically. RESULTS:
      There was an association between the TS-low group and the responders (p < 0.05);
      the DPD-low group and the responders in both biopsy and surgical specimens (p <
      0.01). A combination of the low-TS and low-DPD group was further associated with
      responders (p < 0.01). The immunoexpressions of biopsied and surgical specimens
      were significantly associated with each other. CONCLUSION: Neoadjuvant
      chemotherapy for primary gastric cancer with one cycle of 5-FU and cisplatin was
      associated with histological findings in patients with low baseline TS and DPD.
      This dual determination may predict for efficacy of neoadjuvant treatment with
      these drugs.

PMID- 16809150
TI  - Rat PSP94 inhibits the growth and viability of the rat adenocarcinoma cell line
      PAIII in vitro.
AB  - Previous studies have shown that human PSP94 can inhibit the growth of prostate
      cancer cells both in vitro and in vivo. To further validate this potential and
      investigate the protein within a homologous setting, we examined the effects of
      rat PSP94 on the growth of the rat prostate adenocarcinoma cell line PAIII in
      vitro. To generate rat PSP94, we used both a plasmid-based expression system and
      a recombinant rat PSP molecule. Rat PSP was shown to inhibit the growth and
      survival of PAIII cells in a dose-dependent manner with > 90 percent reductions
      in both observed. TUNEL and Annexin-V assays confirmed PAIII cell death to be via
      apoptosis.

PMID- 16809151
TI  - Salvage therapy with oral etoposide in recurrent and/or metastatic squamous cell
      carcinoma of the head and neck.
AB  - BACKGROUND: The purpose of this retrospective evaluation was to assess the
      palliative effect of oral etoposide in heavily pretreated patients with squamous
      cell carcinoma of the head and neck. PATIENTS AND METHODS: Between October 1995
      and February 2003, a total of 26 patients with metastatic and/or recurrent
      squamous cell carcinoma of the head and neck (SCCHN) were treated with oral
      etoposide. Therapy consisted of etoposide at a total dose of 100 mg daily for 7
      days and was repeated every 4 weeks until progression of disease or for a maximum
      of 8 courses. Eighteen patients underwent primary surgery of the tumour followed
      by adjuvant irradiation or surgery after neoadjuvant radiochemotherapy. Eight
      patients had primary irradiation with or without concomitant chemotherapy. All
      patients previously received at least one palliative chemotherapy with
      cisplatin/5-floururacil (5-FU) or cisplatin/taxotere. Patients did not routinely
      receive anti-emetic medication. RESULTS: All patients were eligible for toxicity
      and survival assessment, and 24 of 26 patients for response evaluation according
      to an intention-to-treat principle. Two patients had a partial response (8
      percent); disease was stable in 9 patients (35 percent) and progressed in 13
      patients (50 percent). The median time to progression for all patients was 3
      months (range, 2-54), and median overall survival was 10 months (range, 2-52).
      Toxicity was in general mild and moderate (Grade 1 and 2), except three patients,
      who experienced Grade 3 anaemia, and one patient who had Grade 3 thrombocytopenia
      without bleeding complications. Severe nonhematologic adverse reactions were not
      seen, except for alopecia. CONCLUSION: Our data suggest that oral etoposid is
      markedly effective, in regard to stabilization of disease and survival, and an
      excellent tolerated therapy for pretreated patients with recurrent and/or
      metastatic head and neck carcinomas. Its advantage over other commonly used and
      more intensive regimens such as 5-fluorouracil (5-FU) + cisplatin or taxane
      containing combinations is its superior tolerance, in particular the incidence of
      nausea and vomiting, complete alopecia, and/or hematologic complications.

PMID- 16809152
TI  - Methylguanine DNA methyl transferase activities, glutathione s transferase and
      nitric oxide in bladder cancer patients.
AB  - Tumor formation is a multistep process that can be divided in to the stages of
      tumor initiation, promotion, and progression. DNA repair protein; MGMT is a key
      suicide enzyme that repairs the mispairing base methylguanine, which is induced
      in DNA as a minor lesion. The glutathione S transferases (GSTs) are a family of
      enzymes that are important to protect against alkylating agents. Nitric oxide,
      contributes to the regulation of tumor angiogenesis. A substantial body of
      experimental evidence supports the hypothesis that tumor angiogenesis is
      fundamental for the growth and metastasis of solid tumors. We measured the
      activities of GST, MGMT, and levels of NO3-/NO2- in the leukocytes from patients
      with bladder carcinoma and healthy controls and activities of MGMT in the tissue
      from patients with bladder carcinoma and adjacent normal tissue in bladder. Both
      GST and tissue MGMT activites were significantly increased in the patient group.
      There was no significant difference between controls and patients for MGMT
      activity in peripheral blood leukocytes (PBL). Nitrate/nitrite levels in PBL,
      there was no significant difference between controls and patients.
      Nitrate/nitrite levels were increased in G2-G3 tumors. In conclusion, we
      determined high concentrations of nitrite in leukocytes are suspected alkylation
      damage by induction nitrosamine. Increased DNA alkylation damage may lead the
      stimulation of MGMT and GST.

PMID- 16809153
TI  - Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor
      expression in primary cell cultures from human prostate carcinoma.
AB  - Contradictory data have been reported regarding the effect of GnRH agonists and
      antagonists on cell growth and survival, using prostate cancer-derived cell lines
      expressing either endogenous or exogenous GnRH receptors. We addressed the issue
      studying the effect of leuprolide (agonist) and cetrorelix (antagonist) on cell
      growth, apoptosis and GnRH receptor expression using a primary cell coculture
      system. Also, binding characteristics of prostate GnRH receptor in this culture
      system are described. Epithelial and stromal cells were obtained from prostate
      adenocarcinoma samples and cocultured in a bicameral system. Expression of GnRH
      receptors was evaluated by semiquantitative RT-PCR (transcript level) and Western
      blot (protein level). Cell growth was estimated by MTT method and apoptosis by
      DNA fragmentation using COMET assay. Saturation and competition binding studies
      were carried out using 125I-GnRH as radioligand. GnRH receptors from cell
      cultures of prostate cancer exhibited a single class of binding sites with a Kd
      of 1.11 +/- 0.28 nM and a Bmax of 2.81 +/- 0.37 pmol/mg of membrane protein for
      GnRH. Leuprolide and cetrorelix showed no effect on GnRH receptor expression.
      Both analogues showed a significant reduction in cell growth rate and an increase
      in DNA-fragmented cell number. These effects were dependent on the analogue
      concentrations (from 5-20 ng/mL). Considering that the culture system used in
      this work represents more closely the in vivo conditions of tumor cells than
      metastatic derived cell lines, we conclude that GnRH analogues have a significant
      inhibitory effect on cell viability of cells expressing GnRH receptors. In
      addition, GnRH receptors expressed in tumor prostatic cells seem not discriminate
      between agonist and antagonist, both analogues activating these receptors. Also,
      leuprolide and cetrorelix treatments did not influence GnRH receptor expression
      in our culture system. These differences with pituitary receptors may be
      explained by differences in affinity, transduction mechanism and molecular
      context in prostatic tissue.

PMID- 16809154
TI  - Salivary antioxidant capacity in graft versus host disease.
AB  - Stem cell transplantation (SCT)-related salivary gland injury and dysfunction
      result in local and systemic manifestations that may be long lasting and are
      associated with a high rate of morbidity and increased risk of infection. The
      salivary antioxidant system may have a major protective role. We, therefore,
      assessed salivary antioxidant capacity and function in 30 patients who had
      undergone SCT: 18 males and 12 females whose median age was 36 years (range: 7
      58). Salivary gland function was assessed by sialometric and biochemistry means,
      which included measuring total protein, secretory IgA (SIgA) and the antioxidants
      peroxidase, uric acid (UA), and total antioxidant status (TAS) in the collected
      saliva. In patients who developed graft versus host disease (GVHD), we observed a
      significant decrease of the salivary flow rate, from 0.74 +/- 0.14 ml/minute to
      0.19 +/- 0.08 ml/min, pre- and post-SCT, respectively (p < 0.01) with no
      recovery. In contrast, in patients who underwent autologous or allogeneic SCT and
      did not develop GVHD, salivary flow rates returned to normal 3-5 months
      posttransplantation. GVHD also resulted in a concomitant reduction of the
      salivary protein content and the salivary antioxidant capacity. The TAS levels in
      the saliva of the GVHD patients were found to be significantly reduced, to about
      one-third of the base-line value (P < 0.02). The concomitant reduction in
      salivary flow rate, protein content, and antioxidant capacity may well explain
      the GVHD-induced oral and gastrointestinal tract (GIT) mucositis, as the saliva
      constantly swallowed into the GIT losses its usual antioxidant protective roles.
      In conclusion, our findings may point at a possible new mechanism for the
      pathogenesis of oral and intestinal mucositis in pre-GVHD patients. Therapy with
      artificial saliva and free radical scavengers and/or antioxidants (administered
      either systemically or via oral rinses) thus, may be of clinical relevance.

PMID- 16809155
TI  - Multifocal osteosarcoma involving unusual sites.
AB  - We report a rare case of multifocal osteosarcoma (MFOS) with involvement of
      skeleton, lung, bone marrow, and soft tissues, presenting with paraparesis,
      cranial nerve palsies, subcutaneous nodules, anemia, and thrombocytopenia. MFOS
      with involvement of unusual sites presents problems in diagnosis and has a poor
      prognosis. The literature on 11 cases of MFOS with extraosseus, extrapulmonary
      involvement reported previously has been reviewed.

PMID- 16809156
TI  - Alteration of pemetrexed excretion in the presence of acute renal failure and
      effusions: presentation of a case and review of the literature.
AB  - Pemetrexed is a multitargeted antifolate approved by the Food and Drug
      Administration for patients with mesothelioma and non small cell lung cancer. As
      this agent is almost exclusively cleared by renal excretion, trials leading to
      its approval were conducted in patients with normal renal function. However, this
      cycle active agent often is administered with cisplatin to patients who may have
      pleural effusions and ascites. As a result, the potential for drug accumulation
      in effusions and for accompanying renal insufficiency is real. Recommendations
      for the management of pemetrexed toxicity in the presence of renal failure have
      not been established. A case of treatment-related acute renal failure following
      chemotherapy with cisplatin and pemetrexed in a patient with advanced
      mesothelioma and ascites is presented. Pharmacologic studies in this patient
      revealed persistent pemetrexed levels in ascites and plasma. This is the first
      time that significant accumulation of pemetrexed in ascetic fluid has been
      reported in the literature. Treatment with leucovorin, folate, and continuous
      veno-venous hemodialysis was initiated. Thymidine and carboxypeptidase were not
      available. Dialysis was unsuccessful in removing pemetrexed. Theoretical and
      practical approaches to management of similar cases are presented.

PMID- 16809157
TI  - Application of smoothing methods to evaluate treatment-prognostic factor
      interactions in breast cancer data.
AB  - In breast cancer research, investigators often are interested in knowing any
      pattern of change in efficacy of a hormonal or chemo therapy over a continuum of
      a prognostic factor such as age or hormonal receptor level. Bonetti and Gelber
      (1) introduced a graphical method to evaluate treatment-covariate interactions by
      using the Cox model (2, 3). By combining their concepts and the well-known
      locally weighted regression smoothing procedure, Fisher, Jeong, Bryant et al. (4)
      evaluated pattern of average annual recurrence rates as a continuous function of
      age among breast cancer patients with histologically negative lymph nodes and
      positive estrogen receptors. In this article, we elaborate on the combined
      exploratory smoothing technique to evaluate an interaction between treatment
      effect and hormonal receptor level among breast cancer patients with positive
      estrogen receptors and positive progesterone receptors. The results reveal that
      the patients with higher estrogen receptor level tend to benefit more from
      tamoxifen and the incremental benefit from adding a chemotherapy to tamoxifen
      tend to be greater for the patients with lower estrogen receptor level. The
      progesterone level does not affect the size of benefit from tamoxifen, but the
      benefit from the addition of the chemotherapy is greater for patients with higher
      progesterone level.

PMID- 16809158
TI  - Health consequences of the September 11 World Trade Center attacks: a review.
AB  - In the aftermath of the September 11 World Trade Center (WTC) attack, a large
      number of people sustained potential exposures to smoke, dust, particulate
      matter, and a variety of toxins, including asbestos, pulverized concrete, glass
      fibers, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated furans and
      dioxins. Additionally, many had exposure to psychological traumatogens. The most
      common effects seen to date are respiratory and mental health consequences. The
      long-term consequences of exposures are not yet known, and there remains concern
      about the potential for late-emerging diseases such as cancers. This article
      reviews WTC-related health effects, the spectrum of exposures and how they were
      documented, and discusses future preventive efforts.

PMID- 16809159
TI  - Recent advances in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia is a low-grade B-lineage lymphoid malignancy. Based
      on recent findings, the disease appears to be more heterogeneous than previously
      thought. Many cases may require no treatment at all unless patients become
      symptomatic or develop signs of rapid progression. Even in this setting,
      treatment is noncurative and is directed at reducing the symptoms. Recently
      described molecular risk features may help delineate at initial diagnosis which
      patients will have a more aggressive course. Newer treatment regimens
      incorporating purine nucleoside analogs and monoclonal antibodies have increased
      the rate of molecular complete remissions, which may lead to increased survival.
      Reduced intensity conditioning regimens have made the potentially curative
      modality of allogeneic transplantation more widely available. All of these recent
      treatments have significant risks of infectious complications, which must be
      carefully weighed against the risks posed by the underlying disease, and many low
      risk asymptomatic patients do not require any treatment. A proposed risk-based
      treatment algorithm will be discussed.

PMID- 16809160
TI  - Evaluation of gefitinib for treatment of refractory solid tumors and central
      nervous system malignancies in pediatric patients.
AB  - Gefitinib (ZD1839, Iressa), a member of the 4-anilinoquinazoline class of
      compounds, has the chemical name 4-quinazolinamine, N-(3-chloro-4-flurophenyl)-7
      methoxy-6-[3-(4-morpholinyl)propoxy]. Gefitinib often is referred to as a
      "specific" or "selective" inhibitor of epidermal growth factor receptor (EGFR).
      EGFR expression has been noted in neuroblastoma and rhabdomyosarcoma cell lines
      and in tumor specimens from children with Wilms tumor, osteosarcoma, and glioma.
      Thus, gefitinib, the first marketed EGFR tyrosine kinase inhibitor, was chosen
      for study in children with refractory solid tumors and central nervous system
      (CNS) malignancies. This review discusses findings from 3 clinical trials of
      gefitinib in children with refractory solid tumors and CNS malignancies, focusing
      on the clinical pharmacology of the compound. To date, gefitinib has been studied
      in children as a single agent and in combination with irinotecan. Overall, the
      compound has been well tolerated in children and has a safety profile similar to
      that observed in adults. The clinical pharmacokinetics of gefitinib in children
      are similar to those observed in adults. Finally, the future for the use of
      gefitinib in pediatrics is similar to that of other molecularly targeted agents
      and awaits definition of tumors and patient populations in which it will be most
      advantageous.

PMID- 16809161
TI  - Approaching clinical problems in prostate cancer radiotherapy using the number
      needed to treat (NNT) technique.
AB  - The goals of this article are to review the application of the number needed to
      treat (NNT) concept to selected clinical problems in prostate cancer
      radiotherapy. Particular emphasis will be placed on (1) comparison of
      radiotherapy with other treatment options for early-stage disease, (2) the role
      of hormone therapy in addition to radiotherapy over a spectrum of disease
      presentation, and (3) systematic comparison of adjuvant versus salvage
      radiotherapy in the post-prostatectomy setting. Limitations of NNT calculations
      based on non-randomized comparisons also are discussed.

PMID- 16809162
TI  - Management of bone loss induced by aromatase inhibitors.
AB  - Aromatase inhibitors are quickly becoming standard adjuvant endocrine therapy for
      hormone-receptor positive breast cancer, either upfront or in sequence after
      tamoxifen. As other means of estrogen-depleting therapy, decreasing bone mineral
      density is the major side effect of this treatment. As increase in fracture
      incidence have already been reported in most major trials of aromatase
      inhibitors. Bisphosphonates are used to treat this cancer-treatment induced bone
      loss, the available data is reviewed here.

PMID- 16809163
TI  - Why did he die?
AB  - The true reason why cancer patients die is not absolutely clear. The decreasing
      rate of postmortem examinations in this group of patients is discussed.
      Understanding how cancer cells kill people can elucidate therapeutic approaches
      that might benefit our patients. Finally, the author pledges to support research
      to understand the reason why many of our patients die.

PMID- 16809164
TI  - Limitations of epidemiological and serologic studies addressing simian virus 40
      and non-Hodgkin's lymphoma.

PMID- 16809165
TI  - Response to "A Porsche for patient accrual," by David Steinberg, Cancer
      Investigation, 2005, 23(8), pp. 741-743.

PMID- 16809167
TI  - Do needle syringe programs reduce HIV infection among injecting drug users: a
      comprehensive review of the international evidence.
AB  - This first international review of the evidence that needle syringe programs
      reduce HIV infection among injecting drug users found that conservative
      interpretation of the published data fulfills six of the nine Bradford Hill
      criteria (strength of association, replication of findings, temporal sequence,
      biological plausibility, coherence of evidence, and reasoning by analogy) and all
      six additional criteria (cost-effectiveness, absence of negative consequences,
      feasibility of implementation, expansion and coverage, unanticipated benefits,
      and application to special populations). The Bradford Hill criteria are often
      used to evaluate public health interventions. The principal finding of this
      review was that there is compelling evidence of effectiveness, safety, and cost
      effectiveness, consistent with seven previous reviews conducted by or on behalf
      of U.S. government agencies. Authorities in countries affected or threatened by
      HIV infection among injecting drug users should carefully consider this
      convincing evidence now available for needle syringe programs with a view to
      establishing or expanding needle syringe programs to scale.

PMID- 16809168
TI  - Thinking ethically about needle and syringe programs.
AB  - Accepting-for the sake of argument-our current legal policies concerning heroin
      use and its users, what ethical questions are raised for needle and syringe
      program (NSPs)? Do they weaken drug laws, send the wrong message or obscure the
      right message, do little to eliminate the harm of drugs, detract from
      alternatives, and/or constitute a counsel of despair? I suggest that in the
      absence of established better alternatives, NSPs constitute a morally acceptable
      and in some cases even desirable option despite the continued criminalization of
      injecting drug use. Yet they must be conceived and administered in ways that do
      not reinforce prevailing social prejudices.

PMID- 16809169
TI  - Critical condition facing needle exchange programs: the politics of science.

PMID- 16809170
TI  - Research-informed policy: our most critical unresolved issue in AIDS.

PMID- 16809171
TI  - The prevention and care of HIV-infected drug users in contemporary Brazil.

PMID- 16809172
TI  - Needle and syringe exchange programs in Amsterdam.

PMID- 16809173
TI  - Lessons from the first international review of the evidence for needle syringe
      programs: the band still plays on.

PMID- 16809174
TI  - Needle exchange and the HIV outbreak among injection drug users in Vancouver,
      Canada.

PMID- 16809175
TI  - Threat or opportunity? Secondary exchange in a setting with widespread
      availability of needles.
AB  - Where authorized access to needles and syringes from exchanges and pharmacies is
      limited, secondary exchange (SE) can provide an important source of sterile
      injecting equipment. Interventions can be developed to use SE to facilitate
      needle and syringe exchange programs to reach a wider population of drug
      injectors. Yet in a context such as Western Australia, where needles and syringes
      are available to drug injectors from many authorized sources, the added benefit
      of SE is unknown. This review of data and literature conducted in October 2003
      shows potential benefits but also concerns about undermining vulnerable public
      and political support for authorized needle provision schemes that has been
      nurtured and supported over a number of years.

PMID- 16809176
TI  - Secondary syringe exchange among users of 23 California syringe exchange
      programs.
AB  - This article describes the secondary syringe exchange (SSE) practices of
      injection drug users (IDUs) attending 23 syringe exchange programs (SEPs) in the
      state of California during 2002 (n=539). The sample was primarily heroin
      injecting, about two thirds male, half White and half other racial/ethnic groups.
      Participants were interviewed with a structured questionnaire that included items
      on sociodemographic factors, drug use practices, sexual practices, use of SEP and
      other social services, and satisfaction with SEP services. Interviews lasted
      about 30 minutes. SSE was highly prevalent: 75% of IDUs reported participating in
      SSE in the 6 months before interview. Program characteristics, such as legal
      status, SSE policy, and exchange policy, did not affect the prevalence of SSE
      among SEP clients. Infectious disease risk behaviors were significantly more
      common among SSE participants than nonparticipants. SSE participants were more
      likely to share syringes (p<.001) and cookers (p<.001) in the previous 6 months.
      SSE was significantly associated with being stuck with another person's syringe
      (needle-stick), a little-discussed "occupational hazard" of this practice. In
      multivariate analysis, the adjusted odds ratio of needle-stick among SSE
      participants was 2.8 (95% confidence interval, 1.3, 6.0). The high prevalence of
      SSE and the infectious disease risk associated with it warrant additional
      research to determine the causality of these associations. In the interim, SEPs
      should consider reinforcing HIV prevention education messages and training IDUs
      who engage in SSE in safe handling of biohazardous materials.

PMID- 16809177
TI  - Factors associated with buying and selling syringes among injection drug users in
      a setting of one of North America's largest syringe exchange programs.
AB  - We performed analyses of syringe buying and syringe selling among Vancouver
      injection drug users, recruited from May 1996 and followed up between November
      2002 and August 2003, in the context of one of North America's largest syringe
      exchange programs (SEPs). An interviewer-administered questionnaire,
      approximately 45 minutes in duration, was used to collect information regarding
      risk factors for HIV infection and sources of sterile syringes. Seventy
      participants (15%) reported syringe selling and 122 (26%) reported syringe
      buying. Syringe sellers were more likely to be female, reside in unstable
      housing, need help injecting, and have visited the SEP at least once weekly.
      Syringe buyers were more likely to need help injecting, have difficulty finding
      new syringes, have binged on drugs, and have visited the SEP at least once
      weekly. Syringe buying most frequently occurred when the SEP was closed.

PMID- 16809178
TI  - Social context of needle selling in Baltimore, Maryland.
AB  - Although much of the debate surrounding the distribution of sterile syringes to
      injection drug users (IDUs) has focused on needle exchange programs (NEPs), IDUs
      acquire their syringes from three major sources: NEPs, pharmacies, and secondary
      exchangers or needle sellers. The purpose of the present study is to examine
      types and frequencies of social interactions among drug injectors who sell
      needles, most of which come from NEPs, compared with individuals who do not sell
      needles. Specifically, we compared engagement in drug-related behaviors, roles in
      the drug economy, and social network membership. Data were collected as part of
      the SHIELD study, an HIV prevention intervention targeted at drug users and their
      social networks (n=910) from February 2001 through September 2003 in Baltimore,
      Maryland (USA). In this sample, 56 participants reported selling needles. Needle
      sellers had higher levels of engagement in drug-related social interactions,
      including using drugs with others, giving or receiving drugs from others, and
      buying drugs with other users. Participants who sold needles had a significantly
      higher number of roles in the drug economy. Also, they had more social network
      members who were injectors, with whom they talked about risky drug behaviors,
      gave needles to, and shared cookers and bleach with. Compared with nonselling
      injectors, needle sellers engage in HIV risk-related behaviors, such as injecting
      daily and sharing injection equipment, more frequently. The study's findings may
      be useful to determine whether secondary exchangers should be targeted for HIV
      prevention activities both to reduce their own risk and to diffuse risk reduction
      information throughout the drug using community.

PMID- 16809179
TI  - An exploratory qualitative study of polydrug use histories among recently
      initiated injection drug users in San Juan, Puerto Rico.
AB  - It is well documented that drug users often modulate the effects of their primary
      drugs of use (e.g., cocaine) by using other drugs (e.g., alcohol), yet the effect
      of modulating and primary drug interactions on transitions from one class of
      drugs to another and from noninjected drugs to injected drugs is not clear. This
      issue, which is critical for understanding polydrug abuse,1 is explored in
      formative research based on in-depth qualitative interviews conducted during 2003
      2004 with 25 recently initiated drug injectors residing in San Juan, Puerto Rico.
      This study suggests that increased use of a primary drug (e.g., cocaine) was
      influenced by enhancing or attenuating drugs, which were used in a particular
      order (e.g., alcohol, heroin) reflecting effectiveness in modulating primary
      drugs at different use intensities, as well as by participants' perceptions of
      the relative dangers associated with different drugs. Neither availability nor
      access appeared to affect the order in which participants used modulating drugs.

PMID- 16809180
TI  - Assessing needle exchange operations in a poor Brazilian community.
AB  - This article assesses the operations of Porto Alegre, State of Rio Grande do Sul,
      (southern Brazil) needle exchange program (NEP), a setting where HIV infection
      rates have been on the rise among injection drug users (IDUs) in recent years,
      contrasting with substantial declines observed in this population, in major
      Brazilian cities (located in the southeast and southernmost part of Brazilian
      northeast). We explored local syringe dynamics, with the exclusive delivery in
      the local NEP of tagged syringes, and the subsequent monitoring of returned
      tagged/untagged used syringes from January to September 2002. We further assessed
      local NEP operations using focus groups and field observation, trying to expose
      the underlying reasons for the substantial delay in the return of tagged syringes
      and the continuous and relevant return of untagged syringes throughout the study
      period. We found that local IDUs reuse, divert, and create caches of syringes at
      their discretion. All efforts should be made to increase the availability of
      clean syringes and to fully integrate syringe exchange with comprehensive health
      education and health screening to effectively curb HIV spread.

PMID- 16809181
TI  - Needle syringe acquisition and HIV prevention among injecting drug users: a
      treatise on the "good" and "not so good" public health practices in South Asia.
AB  - This article describes the prevalence of HIV/AIDS and other bloodborne infections
      is well established among injection drug user (IDU) populations in South Asia
      (SA). IDU populations in SA are diverse and display different demographic and
      socioeconomic profiles. The current provision of sterile injecting equipment as
      part of public health initiatives is suboptimal. Although some needle and syringe
      exchange programs (NSEPs) operate in the region, pharmacies and "friends"
      continue to be a major source of syringe acquisition. It is suggested that the
      cost of syringes in the region is significantly higher in real terms than in
      several other countries and negatively impacts on the ability of IDUs to acquire
      needles and syringes. In addition, existing NSEPs offer poor coverage both at the
      population and individual level. Their effective functioning is hampered by
      resource constraints, ambivalent policy positions, little attention to quality,
      and environmental factors. Secondary syringe exchange is a nascent phenomenon in
      SA that needs to be adequately documented and evaluated. Urgent attention needs
      to be given to developing alternative models of needle syringe delivery to scale
      up HIV prevention interventions for IDUs. This study was conducted in the first
      quarter of 2004 and updated in 2006. We used key informants, previously
      unpublished and published data from research studies, and interventions programs,
      service statistics, and primary data to inform this study.

PMID- 16809182
TI  - Secondary syringe exchange as a model for HIV prevention programs in the Russian
      Federation.
AB  - Effective prevention of syringe-borne transmission of HIV and the hepatitis
      viruses can be undermined if contact between injection drug users and the staff
      of prevention programs is impeded by police harassment, limited program
      resources, and the absence of an open "drug scene." All these are commonplace in
      the Russian Federation. In response, "Project Renewal," the harm reduction
      program of the AIDS Prevention and Control Center of the Tatarstan Ministry of
      Health in Kazan, has created a hybrid syringe exchange program that as its
      primary focus recruited and trained volunteers to provide secondary syringe
      exchange. To compensate for operational barriers, the program staff identified
      private venues and trained responsible individuals to work through their own and
      related networks of injectors to provide clean syringes, other harm reduction
      supplies, and educational materials, while facilitating the collection and
      removal of used and potentially contaminated syringes. Program staff developed a
      detailed set of tracking instruments to monitor, on a daily and weekly basis, the
      locations and types of contacts and the dissemination of trainings and materials
      to ensure that the secondary distribution network reaches its target audience.
      Data show that these secondary exchange sites have proven more productive than
      the primary mobile and fixed-site syringe exchanges in Kazan. Beginning in 2001,
      Project Renewal has trained other harm reduction programs in the Russian
      Federation to use this model of reaching injectors, identifying and training
      volunteers, and monitoring results of secondary syringe exchange.

PMID- 16809183
TI  - Motives for and against injecting drug use among young adults in Amsterdam:
      qualitative findings and considerations for disease prevention.
AB  - To elucidate injection initiation and risky injection practices among young drug
      users (YDUs) in Amsterdam, this study identifies self-reported motives for
      injecting and not injecting to inform interventions to be targeted at issues
      personally relevant for this population. A qualitative study was performed using
      in-depth interviews to obtain retrospective drug use histories. Recruitment took
      place both directly (by street outreach, outreach at methadone outposts) and
      indirectly (by respondent-driven sampling). The study started in the year 2001
      and included 50 YDUs, aged 18-30, of which 18 had a history of injecting. Reasons
      for not starting injection were fears of needles, overstepping a limit, damage to
      appearance, fears of missing veins and causing abscesses, and illnesses. Reasons
      for starting injection were stronger effect or rush, curiosity, economy, knowing
      injectors, and perceived lack of danger to health. Motives for injecting and not
      injecting can differ widely individually. Some strong motives are hardly
      addressed by prevention programs and should inform new prevention initiatives.
      Users' own motives for not injecting should be promoted, whereas their motives
      for initiation should be counter-balanced with factual information.

PMID- 16809184
TI  - Changes in the "get-off": social process and intervention in risk locales.
AB  - Because of ongoing resistance in Florida's legislature to interventions involving
      exchanges of sterile syringes for contaminated ones, Miami/Dade County's
      population of injection drug users (IDUs) reduce risk of HIV and hepatitis C
      infection by buying illegal syringes, participating in illegal syringe exchanges,
      or decontaminating their paraphernalia. Although it is completely legal,
      wherewithal for decontamination of injection paraphernalia, including sodium
      hypochlorite (laundry bleach), water, and cotton for filtering drugs, only
      appears sporadically in Miami/Dade's risk locales (called "get-off" houses). To
      ensure consistent decontamination, our intervention instituted regular delivery
      of these goods to known risk locales. In addition, personnel in half of the
      locales received training in techniques for optimal decontamination. RNA
      polymerase chain reaction measured impact of this intervention in terms of viral
      load found on harvested paraphernalia. Regular delivery of cleansing
      paraphernalia provided opportunities for observation and characterization of
      adaptations among people who run risk locales. These people may lead highly
      stable lives or highly changeable ones, but in most cases their roles as regular
      hosts of injection activities continue with only brief hiatuses due to
      incarceration, eviction, or familial dissolution. Proprietors of risk locales
      maintain their roles as facilitators of self-injection because they use that role
      to make money or to obtain opportunities to inject drugs and also because their
      clientele demands they continue.

PMID- 16809185
TI  - A rapid assessment of heroin use in Mombasa, Kenya.
AB  - This article reports on a rapid assessment (RA) carried out in the city port of
      Mombasa, Kenya in March 2004 by the Omari Project to inform the scaling up of
      their services to heroin users. Heroin has been a street drug in Mombasa for over
      25 years. From 1998, white crest, probably from Thailand, started to replace
      brown sugar, and there was a major shift from inhalation of the vapor ("chasing
      the dragon") to injecting. The Omari Project has been monitoring the heroin
      situation in Mombasa and treating heroin users from Mombasa since 1997. In the
      course of the RA, 496 heroin users were interviewed of whom 95% were men and 5%
      were women. A range of methods were used, including mapping of the Mombasa
      region, work with a key informant/guide who was a heroin user, administration of
      a brief questionnaire and informal interviews, and feedback of findings to other
      local agencies working with drug users. Respondents were from a wide range of
      cultural/ethnic groups, the two largest being Mijikenda and Swahili, who are
      indigenous to the Kenya coast. Overall, 15% of respondents had "ever injected"
      heroin, and 7% were current injectors (n = 37). These data indicate a shift away
      from injecting but also reflect the death of many established injectors, either
      through overdose or AIDS or hepatitis. The figure of 7% of the sample reporting
      being current injectors is likely to be an underestimate. Syringes were available
      from a number of pharmacies and most injectors reported using a syringe for 1-3
      days. The majority reported injecting in a group of three or more and described
      risk behaviors for HIV transmission. The results of the assessment highlight the
      need for a range of services, including needle exchange, counseling, and referral
      to residential treatment programs. However, progress toward responding to the
      findings of the RA by establishing effective services are hampered because of
      legal impediments to operating needle exchange programs in Kenya.

PMID- 16809186
TI  - Rethinking coverage of needle exchange programs.

PMID- 16809188
TI  - Treatment of gustatory sweating with low-dose botulinum toxin A: a case report.
AB  - Frey's syndrome, gustatory sweating in the preauricular area, is an unpleasant
      phenomenon occurring during meals after surgery on the parotid gland. Recently,
      botulinum toxin A (BTX) has been shown to reduce the symptoms, but the variation
      in the reported doses is large. OBJECTIVE: To quantify the effect of treatment
      with low-dose BTX in a case of Frey's syndrome over a period of 6 months.
      MATERIAL AND METHODS: A 56-year-old woman was treated with 10 U Botox given as 20
      single, intracutaneous injections of 0.5 U, one for each cm(2), 3 years after
      resection of the parotid gland. Before treatment and repeatedly during the 6
      month period, the sweating was rated subjectively on a 100-mm visual analog scale
      (VAS) and by a severity index, and objectively by assessment of the extent of the
      involved skin area using Minor's iodine-starch test, staining the area of
      sweating dark. RESULTS: The treatment decreased the involved area from 20 to 5
      cm(2) and the VAS ratings from 98 to 8 mm. The index showed that treatment
      affected the sweating intensity, not the frequency. After the 6-month period the
      patient was still satisfied, but the involved skin area had increased; however,
      not entirely to pretreatment values. CONCLUSIONS: The effect of BTX injections
      for gustatory sweating obtained in this case was comparable to results reported
      using higher doses. Low doses of BTX can therefore be used in the treatment of
      Frey's syndrome, but studies to clarify the dose-response relationship, in terms
      of both time-course and obtained effect, are needed.

PMID- 16809189
TI  - First molar eruption related to plaque acidogenicity in children of different
      socio-economic status.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between the
      eruption stage of the lower first permanent molar and dental plaque
      acidogenicity. Socio-economic status (SES), gender, and oral hygiene condition
      were also variables considered. MATERIAL AND METHODS: 230 children between 6 and
      8 years of age were recruited from one public and one private primary school with
      different SES in Lima, Peru. Clinical examinations were performed to assess lower
      first permanent molar eruption stage, plaque acidogenicity, and oral hygiene
      condition. Bivariate associations were analyzed through chi-square tests and the
      variable interactions were analyzed through a hierarchical log-linear analysis
      with backward elimination. RESULTS: 21.8% of the population had highly acidogenic
      plaque, 34.3% acidogenic plaque, and 43.9% non-acidogenic plaque. Of the lower
      first permanent molars, 46.1% were fully erupted, whereas 53.9% were partially
      erupted. According to the final log-linear model, children with fully erupted
      molars and non-acidogenic plaque are less frequent in low than in high SES. Also,
      the frequency of children with partially erupted molars and acidogenic to highly
      acidogenic plaque is higher in males than in females. Finally, fully erupted
      molars and non-acidogenic plaque are more frequent in children with good hygiene
      than in children with moderate to poor hygiene. CONCLUSIONS: Association between
      eruption stage of the lower first permanent molar and plaque acidogenicity was
      not significant in a bivariate context. However, in a multivariate context, socio
      economic status, oral hygiene condition, and gender had an impact on the
      association between the two main variables.

PMID- 16809190
TI  - Dye staining gap test: an alternative method for assessing marginal gap formation
      in composite restorations.
AB  - OBJECTIVE: The aim of this study was to evaluate and compare marginal adaptation
      of composite restorations assessed by a dye staining method and by scanning
      electron microscopy (SEM) analysis. MATERIAL AND METHODS: Twenty bovine incisors
      were selected and ground flat to expose dentin. Two cylindrical cavities were
      prepared on the central area of flattened surfaces. Single bond adhesive system
      was applied in accordance with the manufacturer's instructions and the cavities
      were filled with Filtek Z250 or Filtek Flow. The specimens were polished and
      replicas were obtained in epoxy resin. The replicas were observed by SEM for
      marginal quality/quantity evaluation. Caries detector was then applied on each
      specimen for 5 s to verify marginal adaptation through dye staining of the formed
      gaps on the outer margins. Images of the stained gaps were transferred to a
      computer measurement program to determine gap length. The length of the gap was
      expressed as the percentage of total length of the margins observed. Data were
      submitted to two-way ANOVA and Pearson correlation. RESULTS: Filtek flow showed
      36% and 34% and Filtek Z250 27% and 29% of gap in the margins when evaluated by
      SEM analysis and by the dye staining test, respectively. There was no difference
      between the composites, regardless of the evaluation technique. There was a
      strong positive correlation (r=0.83) between the results obtained with the tested
      methods to assess marginal gap. CONCLUSION: Dye staining the gaps can be used
      with good reliability to evaluate the gap formation in composite restorations.

PMID- 16809191
TI  - Recalibration improves inter-examiner reliability of TMD examination.
AB  - OBJECTIVE: The purpose of this study was to assess whether recalibration of
      examiners would improve the reliability of gathering clinical findings and
      related diagnoses of temporomandibular disorders (TMD) in accordance with the
      Research Diagnostic Criteria for TMD (RDC/TMD). MATERIAL AND METHODS: Two
      clinicians independently examined a total of 48 symptomatic and asymptomatic
      subjects according to the RDC/TMD on two occasions: examination 1 (E1). Aarhus,
      Denmark (n=24; 18 female, ages 18-59 years); examination 2 (E2). Malmo, Sweden
      (n=24; 18 female, ages 18-86 years). The clinicians were calibrated in the use of
      the RDC/TMD Axis-I examination on the day before E1. Six months later, they were
      recalibrated on the day before E2. Intra-class correlation coefficients (ICCs)
      were used to examine the inter-examiner reliability of the two clinicians on the
      two occasions (E1, E2). RESULTS: The intra-class correlation coefficients of
      vertical range of jaw motion differed little between E1 and E2. At E2, all other
      examination components consistently improved in reliability relative to E1.
      Similar improvements were seen for the frequently occurring RDC/TMD clinical
      diagnoses: Ia. Myofascial pain [ICC = 0.83 (E1) and 1.00 (E2)], IIa. Disk
      displacement with reduction [ICC = 0.26 (E1) and 0.64 (E2)], and IIIa. Arthralgia
      [ICC = 0.16 (E1) and 0.73 (E2)]. CONCLUSION: Recalibration considerably improved
      inter-examiner reliability for assessing RDC/TMD clinical variables and
      diagnoses, which are critically dependent on reliable assessment of clinical
      signs; improvement was most marked when initial inter-examiner reliability was
      low. Final inter-examiner reliabilities after recalibration were all associated
      with acceptable to excellent levels.

PMID- 16809192
TI  - Potentiation of the bactericidal activity of Harungana madagascariensis Lam. ex
      Poir. (Hypericaceae) leaf extract against oral bacteria using poly (D, L-lactide
      co-glycolide) nanoparticles: in vitro study.
AB  - Harungana madagascariensis Lam. ex Poir. (Hypericaceae) is known to have
      biological properties with mainly antibacterial, antifungal, and antiviral
      effects. The objective of this study was to investigate the in vitro bactericidal
      activity of the ethyl acetate H. madagascariensis leaf extract (HLE) on the main
      oral bacterial strains largely implicated in dental caries and gingivitis
      infections, and the possibility of potentialization of HLE antibacterial effects
      using the poly (D,L-lactide-co-glycolide) nanoparticles (PLG-NP). The
      microdilution technique and the interfacial polymer deposition following the
      solvent diffusion method were used to investigate the in vitro bactericidal
      activity of ethyl acetate HLE and to prepare nanoparticles, respectively. HLE
      showed significant bactericidal effects against the bacterial strains tested,
      with minimal bactericidal concentration (MBC) to 5 x 10(2) mg/l or less, except
      for Lactobacillus casei with 7.5 x 10(2) mg/l. With the HLE incorporated into PLG
      nanoparticles (HLE-PLG-NP), we observed diminution of the bactericidal
      concentration compared to HLE, the upper MBC being of 1.875 x 10(2) mg/l.
      Incorporation of the HLE into a colloidal carrier optimized its antibacterial
      performance.

PMID- 16809193
TI  - Effect of surface preparation using ethyl acetate on the repair strength of
      denture base resin.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of surface
      preparation using ethyl acetate on the repair strength of a denture base resin.
      MATERIAL AND METHODS: Bar specimens were fabricated with a heat-processed denture
      base resin and cut in half. The repair surfaces of the specimens were treated
      with ethyl acetate for varying amounts of time before the autopolymerizing repair
      resin was applied. The specimens were then immersed in 37 degrees C distilled
      water for 2 days. A three-point bending test was used to determine the transverse
      strength of the test specimens. Ten specimens prepared using a 120-s application
      of ethyl acetate and 10 specimens prepared using a 5-s application of
      dichloromethane were thermocycled at 10,000 cycles (at 5 degrees C and 55 degrees
      C) with a 60-s dwell time. The morphological changes in the repair surfaces after
      preparation were observed by scanning electron microscopy. RESULTS: The repair
      strength of the denture base resin prepared using ethyl acetate for 120 s (30.6
      MPa) was the highest among the results for the various amounts of time tested
      (p<0.05). There were no significant differences between the repair bond strength
      both before and after thermocycling of the denture base resin prepared using
      ethyl acetate for 120 s and that of the denture base resin prepared with
      dichloromethane for 5 s (p>0.05). CONCLUSION: Within the limitations of the
      current study, a 120-s application of ethyl acetate was as effective as a 5-s
      application of dichloromethane at preparing the surfaces of a denture base resin.

PMID- 16809194
TI  - Microbiological diagnostics in oral diseases.
AB  - Most infections of the oral cavity, including the major dental diseases caries
      and periodontitis, are opportunistic in nature. They are caused or maintained by
      microorganisms of the resident or transient flora normally present in low numbers
      and not pathogenic, but in certain circumstances develop infections. Mucosal
      infections have some degree of specificity [e.g. Candida spp., Staphylococcus
      aureus, and enterics] and a microbiological test can be interpreted accurately
      for clinical diagnosis and choice of treatment. Subepithelial or deep infections,
      however, include a number of species from the resident flora, mainly anaerobes
      whose role in the infections is difficult to interpret. However, microbiological
      tests and the presence of certain bacterial species could be used for treatment
      control, risk-evaluation and even for patient motivation in the prevention of
      these diseases. Microbiological diagnosis can be used in general practice for
      several purposes and in various situations that can be of great value for the
      dental patient.

PMID- 16809195
TI  - Gender differences in tooth loss among Chilean adolescents: socio-economic and
      behavioral correlates.
AB  - OBJECTIVE: To investigate gender differences in tooth loss among Chilean
      adolescents and its association with selected socio-economic indicators and oral
      health-related behaviors. MATERIAL AND METHODS: Data on 9,163 Chilean adolescents
      obtained using multistage random cluster procedures. Clinical recordings included
      information on missing teeth and the participants provided information on socio
      demographic factors and oral-related behaviors. Two eruption-time-adjusted
      logistic regression analyses were used to investigate the associations between
      gender, tooth loss and socio-economic position/oral-health-related behaviors.
      RESULTS: The association between gender and tooth loss remained after adjusting
      for age, eruption times in both the socio-economic position regression model and
      the oral-health-related behaviors model. Tooth loss followed social gradients for
      the variables paternal income and achieved parental education, with students
      reporting a paternal income < 100,000 US dollars (OR = 2.0), and having a father
      (OR = 1.8) and a mother (OR = 2.0) who achieved only primary school education
      being more likely to experience tooth loss. The adjusted regression model for
      behavioral indicators revealed that students who reported brushing their teeth
      once a day (OR = 1.6) were more likely to have experienced tooth loss than those
      who reported more frequent toothbrushing. Students who visited a dentist rarely
      (OR = 0.8) or never (OR = 0.5) were less likely to have lost first molars and/or
      incisors. CONCLUSIONS: The results demonstrate that gender differences in tooth
      loss among young Chileans are related to socio-economic position; and selected
      oral-health-related behaviors after adjusting for eruption time variation.

PMID- 16809196
TI  - Association between optimism and self-reported facial pain.
AB  - OBJECTIVE: The objective of this study was to assess the association between
      optimism and self-reported facial pain. MATERIAL AND METHODS: Data were obtained
      for 5,696 subjects born in 1966 in Northern Finland and included in the study of
      the Northern Finland Birth Cohort. Data on facial pain were collected using a
      questionnaire. Optimism was measured using the revised version of the Life
      Orientation Test. RESULTS: The data showed that optimism was inversely associated
      with facial pain. Associations were found only among non-depressive subjects.
      CONCLUSIONS: It can be concluded that optimism is an independent psychosocial
      determinant of pain experience that should be taken into account in assessing the
      prognosis of facial pain and its treatment.

PMID- 16809197
TI  - Bone powder enhances the effectiveness of bioactive glass S53P4 against strains
      of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in
      suspension.
AB  - OBJECTIVE: To assess whether bone powder in suspension enhances the antimicrobial
      efficacy of bioactive glass S53P4 against Gram-negative microbiota commonly
      associated with peri-implant disease. METHODS: Standardized suspensions of
      Porphyromonas gingivalis ATCC 33277 and YH 3, as well as Actinobacillus
      actinomycetemcomitans ATCC 29523 and KK 2 were added to 24-h suspensions of
      bioactive glass S53P4 with ground bovine bone powder, decalcified bone, or
      hydroxylapatite powder. Recovery of viable bacteria was assessed using anaerobic
      culture methods. As a reference, the antibacterial effect of an inert
      borosilicate powder with a particle size corresponding to that of the bioactive
      glass was tested. Counts of bacteria suspended in a pure unbuffered saline
      solution served as controls. RESULTS: A significant drop in viable microorganisms
      was observed in suspensions of bioactive glass and bone powder compared to
      counterparts of pure bioactive glass. In contrast, neither the presence of
      hydroxylapatite powder nor the presence of decalcified bone in suspension caused
      any increase in bioactive glass killing efficacy on the microorganisms under
      investigation. Inert borosilicate glass showed no antibacterial effects per se or
      in combination with bone powder. CONCLUSION: The antimicrobial effect of a
      combined bioactive glass-ground bone powder suspension was an in vitro
      observation which should be confirmed using adequate in vivo models.

PMID- 16809198
TI  - Utilization of pharmaceuticals among patients with temporomandibular disorders: a
      controlled study.
AB  - OBJECTIVE: Pharmaceuticals are among factors that might be associated with
      temporomandibular disorders (TMDs), but knowledge about their utilization is
      limited. The purpose was to systematically register the regular use of medication
      in general among TMD patients and matched controls to enable comparisons to be
      made. MATERIAL AND METHODS: Three hundred consecutive patients referred for
      diagnosis and treatment of TMDs and fulfilling the Research Diagnostic Criteria
      were examined prospectively and any medication recorded. Matched controls were
      registered parallel in time. The pharmaceuticals used were categorized according
      to the Anatomical Therapeutic Chemical Classification System (ATC). RESULTS:
      Forty-four percent of the patients received a main diagnosis of "muscle
      disorder", 39% "disk disorder", and 17% "joint disorder". Fifty-one percent of
      all patients used some medication on a regular basis compared to 36% of the
      controls (p<0.001). The average number of ATC categories used among all patients
      was 0.9 and among controls 0.5 (p<0.001). Of the female patients with the
      diagnosis "muscle disorder", 23% used antidepressants (N06A), 6% tranquilizers
      (N05B), and 7% sleep medication or sedatives (N05C) significantly more frequently
      than controls. Of the female patients diagnosed with a "joint disorder", 26% used
      antidepressants (N06A) significantly more frequently than controls. All other ATC
      categories differed non-significantly. CONCLUSIONS: The results suggest that the
      use of pharmaceuticals differs between patients and controls. TMD patients,
      particularly women diagnosed with "muscle" or "joint" disorders, appear to use
      drugs for depression more frequently than ordinary dental patients.

PMID- 16809199
TI  - Rehabilitation implications of non-traumatic subarachnoid haemorrhage.
AB  - OBJECTIVE: Subarachnoid haemorrhage (SAH) remains an important cause of stroke in
      the rehabilitation population, whose incidence has not been changed by pre-morbid
      medical treatment. The understanding of the pathophysiological changes that occur
      after SAH has been more clearly defined, therefore the treatment and outcomes of
      these patients have undergone drastic changes over the past few years. The
      purpose of this review is to update and familiarize the rehabilitation
      professional on the state of the art treatment and common complications
      associated with this disease and how this may affect the rehabilitation
      programme. Also, the current literature on the outcomes of these patients will be
      reviewed to help advise the rehabilitation professional on potential predictors.
      DATA SOURCES: Literature review. STUDY SELECTION: Articles of relevance to the
      current management of SAH. DATA EXTRACTION: Information that was deemed
      significant in the understanding of the pathophysiology, treatment and results of
      outcomes in patients with SAH. DATA SYNTHESIS: Subarachnoid haemorrhage (SAH) is
      the one sub-type of stroke whose incidence has not declined. Due to advances in
      medical care, mortality rate is on the decline. Outcomes data was analysed to
      look for common predictors for this patient population. CONCLUSIONS: While the
      incidence of SAH has not declined, improving medical treatment has reduced
      mortality. The rehabilitation professional should be familiar with the latest
      advances, potential complications and likely outcomes in order to plan the most
      appropriate therapy course for these patients.

PMID- 16809200
TI  - Challenges associated with the definition and assessment of inappropriate sexual
      behaviour amongst individuals with an acquired neurological impairment.
AB  - The subject of Inappropriate Sexual Behaviour (ISB) amongst clients with
      neurological impairment, specifically Acquired Brain Injury (ABI) and dementia,
      has received limited coverage to date within the literature. This paper discusses
      some of the problems encountered in the definition and quantification of ISB, in
      particular the absence of standardized measurement tools to record ISB within an
      inpatient setting. Whilst ISB is reported to be less prevalent than other
      behavioural sequelae of brain injury or dementia, it is suggested that its impact
      on patients and carers can be significant. Ill-defined terminology and the
      absence of relevant assessment tools add to the specific challenges of
      understanding and managing ISB within a care or rehabilitation setting. As a
      result, it is argued that the subjective attitudes of staff and the culture of an
      institution can dominate the approach taken to dealing with ISB for these client
      groups.

PMID- 16809201
TI  - Post-traumatic amnesia predicts long-term cerebral atrophy in traumatic brain
      injury.
AB  - PRIMARY OBJECTIVE: To examine post-traumatic amnesia (PTA) and its relation to
      long-term cerebral atrophy in persons with traumatic brain injury (TBI) using
      objective indicators of PTA duration and Quantitative Magnetic Resonance Imaging
      (QMRI). It was hypothesized that longer PTA would predict later generalized
      atrophy (increased ventricle-to-brain ratio (VBR)). As a guide in assessing
      patients with TBI, this study determined the probability of developing chronic
      cerebral atrophy based on PTA duration. RESEARCH DESIGN: Probability model using
      60 adult patients with mild-to-severe TBI. MAIN OUTCOMES AND RESULTS: A logistic
      regression model with a cut-off determined by normative QMRI data confirmed that
      longer PTA duration predicts increased VBR. A probability model demonstrated a 6%
      increase in the odds of developing later atrophy on neuroimaging with each
      additional day of PTA. CONCLUSIONS: PTA has previously proven to be a good
      indicator of later cognitive recovery and functional outcome and also predicts
      long-term parenchymal change.

PMID- 16809202
TI  - Effect of urbanicity of residence on TBI outcome at one year post-injury.
AB  - OBJECTIVE: To determine the impact of urbanicity of residence and occurrence of
      medical complications on outcome after traumatic brain injury (TBI). STUDY
      DESIGN: A consecutive series of persons admitted for inpatient TBI rehabilitation
      followed for 1 year post-injury. SETTING: Inpatient brain injury rehabilitation
      programme in the southeastern US. PARTICIPANTS: One hundred and eleven persons
      with severe (67%), moderate (18%) or mild (15%) TBI. OUTCOME MEASURE: Functional
      status at 2 year post-injury as measured by the Disability Rating Scale (DRS).
      RESULTS: Functional status at follow-up was predicted by age, DRS at admission
      for rehabilitation, injury severity, alcohol use, continued need for medications
      and medical complications (validated R2 = 0.57; p < 0.0001). Urbanicity of
      residence was not predictive of functional status. CONCLUSIONS: As expected,
      participants who experienced more medical complications and required continued
      use of medications had poorer functional outcomes. Contrary to expectation, more
      rural residents did not have poorer outcomes than persons residing in more urban
      areas.

PMID- 16809203
TI  - Breaking the news of traumatic brain injury and incapacities.
AB  - PRIMARY OBJECTIVE: This paper presents research results regarding disclosure of
      traumatic brain injury (TBI) diagnosis and resulting deficits of a study aiming
      to investigate the experiences of individuals who had sustained a TBI, their
      families, the physicians and health professionals involved, from the critical
      care episodes and subsequent rehabilitation. RESEARCH DESIGN: Semi-structured
      interviews were conducted with individuals who had sustained a TBI (n = 8) and
      their families (n = 8) as well as with the health professionals (or service
      providers) (n = 22) and physicians (n = 9) who provided them care. MAIN OUTCOMES
      AND RESULTS: Results revealed that the quality of the disclosure is strongly
      influenced by the medical uncertainty surrounding the TBI and the difficulties of
      healthcare professionals in dealing with the family's emotions. CONCLUSIONS:
      Delivering bad news is always difficult, but it is possible to make this
      harrowing experience easier and, in so doing, enhance patient and family
      resilience.

PMID- 16809204
TI  - Work-related deaths and traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) at the workplace is a significant
      contributor to the number of work-related deaths that occur per year. This study
      aimed to quantify and characterize these deaths in Ontario. METHODS: The study
      design was a case series with analytic and surveillance components. Data was
      obtained from the Chief Coroner's Office of Ontario from 1996-2000. RESULTS: A
      total of 488 work-related injury fatalities were identified. Evidence of TBI was
      apparent in 45% of these cases (n = 211). Industries with the highest rate of
      work-related TBI mortality expressed per 100,000 working population included
      primary industry (59.1), agriculture (24.5), construction (20.0) and
      transportation/communications/utilities industries (13.9). Deaths involving TBI
      were more likely to be due to falls than non-TBI-related deaths among workers (p
      = 0.0001). CONCLUSIONS: Results from this research indicate that prevention
      programmes should focus on decreasing falls at all ages and increasing the use of
      personal protective equipment.

PMID- 16809205
TI  - Mild traumatic brain injury: effects on naming in word retrieval and discourse.
AB  - PRIMARY OBJECTIVE: To investigate differences between a group with mild traumatic
      brain injury (MTBI) and a control group relative to standard scores and error
      type during word retrieval in both naming and discourse tasks. METHODS AND
      PROCEDURES: Ten participants with MTBI were age-, gender- and education-matched
      with 10 participants without injury. Pre-experimental tasks for the participants
      with MTBI included the Scales of Cognitive Ability for Traumatic Brain Injury and
      the Raven's Coloured Progressive Matrices and both groups received the Peabody
      Picture Vocabulary Test-III. Experimental tasks included the Test of
      Adolescent/Adult Word Finding and the Test of Word Finding in Discourse. MAIN
      OUTCOMES AND RESULTS: Few participants (three on each experimental task)
      demonstrated psychometrically-based word retrieval deficits (standard score <
      85); however, a significant difference in performance for the TAWF as compared to
      the TWFD was observed between groups. More word finding errors occurred with
      confrontational naming than with discourse tasks for both groups, with latency as
      the primary error type. CONCLUSIONS: Confrontational naming tasks may be more
      sensitive to subtle language difficulties occurring after MTBI. The study of
      adults with MTBI and their performance on semantically-based tasks offers
      important information for the advancement of therapeutic intervention and
      education.

PMID- 16809206
TI  - Symptoms of post-traumatic stress: intrusion and avoidance 6 and 12 months after
      TBI.
AB  - PRIMARY OBJECTIVES: (1) To examine survivors with traumatic brain injury (TBI)
      for symptoms of avoidance and intrusion, two dimensions of post-traumatic stress
      (PTS) at 6 and 12 months post-injury. (2) To identify risk factors associated
      with these symptoms. RESEARCH DESIGN: Prospective follow-up study. METHODS AND
      PROCEDURES: Georgia and North Carolina Model Brain Injury Systems participants (n
      = 198) with mild (19%), moderate (21%) and severe (60%) TBI were interviewed by
      telephone at 6 and 12 months post-injury. The Impact of Event Scale (IES) was
      used to identify intrusion and avoidance symptoms. RESULTS: Symptoms consistent
      with severe PTS increased from 11% at 6 months to 16% 12 months post-injury (p <
      0.003). African-Americans (p < 0.01) and women (p < 0.05) reported greater
      symptomatology at 12 months compared to their counterparts. TBI severity and
      memory of the event were not associated with PTS-like symptoms. Symptoms
      increased over time when examined by race, injury intent, gender and age (p <
      0.05). CONCLUSIONS: Regardless of severity, survivors with TBI are at risk for
      developing symptoms consistent with PTS. Amnesia for the injury event was not
      protective against developing these symptoms. African-Americans appear to be at
      greatest risk.

PMID- 16809207
TI  - Establishing a prognosis for functional outcome during coma recovery.
AB  - PRIMARY OBJECTIVE: One of the most challenging tasks for clinicians caring for
      survivors of severe brain injury (BI) is establishing a prognosis, for long-term
      functional outcome, while the patient is unconscious. The objective of this
      article is to report findings regarding the prediction of functional outcomes 1
      year after severe BI using data available when the patient is unconscious.
      RESEARCH DESIGN: Longitudinal prognostication study. METHODS AND PROCEDURES:
      Persons unconscious after severe BI who present to inpatient (IP) rehabilitation
      hospitals in the Midwestern US are enrolled in an ongoing study. Each subject is
      followed for 1-year and the final outcome interview includes approximately 70
      questions; 32 of these questions are from the Craig Handicap Assessment and
      Reporting Technique (CHART). A sample of 63 persons was abstracted from the study
      database to examine the predictability of 42 independent variables and 16
      dichotomous outcomes. MAIN OUTCOMES AND RESULTS: Twelve of the 16 dichotomous
      outcomes were found to be significantly predictable (p < 0.05). These involve
      activity, participation, environment and quality of life outcomes. Ten predictors
      were found to be significant (p < 0.05): aetiology (Closed Head Injury vs. Other
      BI), presence of urinary tract infection (UTI), seizure, hypertension during IP
      rehabilitation, veteran benefit eligibility, health insurance, marital status at
      injury, whether or not recovery of consciousness occurred within 1 year, the
      number of days between injury and admission to acute rehabilitation and the
      average length of IP rehabilitation stay. Eight of the 10 variables are available
      early after injury or when the patient is unconscious.

PMID- 16809208
TI  - Serum S-100B and cleaved-tau are poor predictors of long-term outcome after mild
      traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To determine the relationship of serum S-100B and C-tau levels
      to long-term outcome after mild traumatic brain injury (mild TBI). RESEARCH
      DESIGN: A prospective study of 35 mild TBI subjects presenting to the emergency
      department. METHODS AND PROCEDURES: Six hour serum S-100B and C-tau levels
      compared to 3-month Rivermead Post Concussion Questionnaire (RPCQ) scores and
      post-concussive syndrome (PCS). MAIN OUTCOMES AND RESULTS: The linear correlation
      between marker levels and RPCQ scores was weak (S-100B: r = 0.071, C-tau: r = 
      0.21). There was no statistically significant correlation between marker levels
      and 3-month PCS (S-100B: AUC = 0.589, 95%CI. 038, 0.80; C-tau: AUC = 0.634, 95%CI
      0.43, 0.84). The sensitivity of these markers ranged from 43.8-56.3% and the
      specificity from 35.7-71.4%. CONCLUSIONS: Initial serum S-100B and C-tau levels
      appear to be poor predictors of 3-month outcome after mild TBI.

PMID- 16809209
TI  - Post-traumatic growth in acquired brain injury: a preliminary small scale study.
AB  - PRIMARY OBJECTIVE: To examine the nature, degree and time course of positive
      psychological change in people with severe acquired brain injury. RESEARCH
      DESIGN: This preliminary exploratory study employed a cross-sectional design,
      comparing two matched samples, one early post-brain injury (M = 7 months) and one
      late post-brain injury (M = 10 years). METHODS AND PROCEDURES: The Posttraumatic
      Growth Inventory (PTGI), Sense of Coherence Scale-13 (SOC-13) and Hospital
      Anxiety and Depression Scale (HADS) were administered. MAIN OUTCOMES AND RESULTS:
      The samples differed significantly with respect to reported post-traumatic
      growth, with the late sample reporting higher levels. HADS anxiety was
      significantly associated with post-traumatic growth. Both samples achieved high
      scores on the SOC-13. CONCLUSIONS: The participants showed evidence of
      substantial positive psychological change, demonstrating that it is not precluded
      by severe brain injury. The results suggest that this develops slowly over time
      and requires a degree of emotional engagement.

PMID- 16809210
TI  - Brain injury following neuroleptic malignant syndrome: case report and review of
      the literature.
AB  - OBJECTIVE: To report a case of brain injury following neuroleptic malignant
      syndrome (NMS) and review the literature for similar documented cases. CASE
      REPORT: A 30-year old woman presented to the ER with psychotic features and was
      treated with several anti-psychotics. Subsequently, she developed neurological
      symptoms and was diagnosed with neuroleptic malignant syndrome. Following a
      prolonged course in an acute care facility, she was admitted to a rehabilitation
      ward, where cognitive and physical examinations revealed significant findings.
      These included marked dysarthria, difficulties comprehending commands, attention
      problems, as well as abnormalities in her muscle tone, power, reflexes, gait, co
      ordination and sensory function. CONCLUSION: Literature reviews reveal few
      documented cases of brain injury following neuroleptic malignant syndrome. A
      further exploration of the effects of NMS on the brain is warranted to elicit
      whether cerebellar damage is indeed common following neuroleptic malignant
      syndrome. Such research could eventually lead to therapeutic interventions aimed
      at preventing permanent brain injury in persons with NMS.

PMID- 16809211
TI  - The association of physical deconditioning and chronic low back pain: a
      hypothesis-oriented systematic review.
AB  - PURPOSE: Does physical deconditioning (loss of cardiovascular capacity and
      strength/endurance of paraspinal muscles) exist in patients with chronic low back
      pain (CLBP) and are treatments specifically aimed to reduce these signs
      effective? METHOD: Systematic literature search in PUBMED, MEDLINE, EMBASE and
      PsycINFO until December 2004 to identify observational studies regarding
      deconditioning signs and high quality RCTs regarding the effectiveness of
      cardiovascular and/or muscle strengthening exercises. Internal validity of the
      RCTs was assessed by using a checklist of nine methodology criteria in accordance
      with the Cochrane Collaboration. RESULTS: There is conflicting evidence that
      cardiovascular deconditioning is present in CLBP and limited evidence for wasting
      of the multifidus muscle. No study examined the effectiveness of cardiovascular
      training specifically. General and lumbar muscle strengthening are equally
      effective as other active treatments. Only moderate evidence is available for the
      effectiveness of intensive low back extensor muscle strengthening compared to
      less intensive strengthening. CONCLUSION: Probably reactivation caused by active
      treatment and not the reconditioning itself is the important factor in the
      reduction of disability. Further prospective and evaluative research into the
      role of physical deconditioning is necessary. It seems more promising to further
      explore the interplay between biological, social and psychological factors.

PMID- 16809212
TI  - The social experience of aging with a chronic illness: perspectives of older
      adults with multiple sclerosis.
AB  - PURPOSE: The purpose of this study was to explore the social experiences of older
      adults with multiple sclerosis (MS) in order to recognize the changes in social
      experience and social needs that may occur with aging with a chronic illness.
      METHOD: Analysis of qualitative data from an exploratory study utilizing a
      phenomenological approach with 27 older adults with MS, aged 55 - 81. RESULTS: In
      depth interviews revealed that the social experience was influenced by groups of
      factors including the person's social needs, experience of MS, values and
      expectations, characteristics of the social support system, the response of the
      support providers, and the accessibility of the social environment. The
      participants discussed concerns about the future adequacy of support. A process
      of negotiation was also described and was seen as an opportunity to change the
      social experience and social support received. CONCLUSION: This study provides an
      insider's view of the social changes that older adults living with MS experience.
      This study also identifies barriers to the acquisition of support and addresses
      the importance of appropriately responding to the changing needs of this
      population.

PMID- 16809213
TI  - An open label pilot investigation of the efficacy of Botulinum toxin type A
      [Dysport] injection in the rehabilitation of chronic anterior knee pain.
AB  - PURPOSE: To examine the effect of intramuscular injection of botulinum toxin type
      A [Dysport] to reduce relative overactivity of the vastus lateralis [VL] muscle,
      in conjunction with re-training of vastus medialis [VM] muscle as an adjunct to
      rehabilitation for chronic anterior knee pain. METHOD: Eight females with chronic
      (>6 months) history of anterior knee pain, who had failed conservative
      management, were studied in this open label pilot study. Intramuscular Dysport
      injection [300 - 500 units] to the distal third of VL muscle was followed by a 12
      week customized home exercise programme to improve recruitment of VM muscle and
      functional knee control. VL and VM muscle cross sectional area from a
      standardized spiral CT sequence, isometric quadriceps strength (dynamometry),
      timed stair task, self-reported pain and disability were assessed. RESULTS:
      Subjects reported reduced knee pain and brace dependency and increased
      participation in sporting and daily living activities. Isometric quadriceps
      muscle strength was maintained or improved despite significant atrophy, evident
      on CT, of the distal component of VL in the treated limb. Time taken to ascend
      and descend a flight of stairs improved in all subjects. Subjective and objective
      improvements were maintained at 24-week follow-up. CONCLUSIONS: These pilot data
      provide preliminary support for the role of Dysport as an adjunct to non-surgical
      management of individuals with chronic anterior knee pain. Larger double blind,
      randomized, placebo-injection controlled studies of this novel approach to
      improving patellofemoral mechanics are needed to establish the efficacy of this
      intervention.

PMID- 16809214
TI  - Distribution of weakness in the upper and lower limbs post-stroke.
AB  - OBJECTIVE: To assess the distribution of weakness in the upper and lower limbs
      post-stroke and the factors associated with weakness. METHOD: The design was a
      prospective cross-sectional survey. A consecutive sample of 75 patients (37 (49%)
      men, mean age 71.5 (SD 12.2) years, 46 (61%) left hemiplegics) with a first-time
      anterior-circulation stroke, tested 2 - 4 weeks post-stroke, were recruited from
      two NHS trusts. MAIN OUTCOME MEASURES: Weakness (Motricity Index, MI). RESULTS:
      Mean MI score was 58.5 (SD 39.6) and 69.1 (SD 33.6) for the upper and lower limb
      (p < 0.001), but examination of individual data indicated 36 (48%) had no/
      negligible difference (0 +/- 9 points) in MI score between the limbs. When there
      was a difference, the lower limb was more frequently the stronger. There was no
      significant difference between the proximal and distal joints in either limb (p <
      0.217 and 0.410). Severity of weakness was not associated with the subjects'
      demographics or stroke pathology, but was associated with neglect and sensation.
      CONCLUSIONS: Although group analysis showed that the leg was significantly
      stronger than the arm, individual analysis showed that most participants had a
      similar degree of weakness in both limbs. When there was a difference, the lower
      limb was more frequently the stronger. Proximal joints were not more severely
      affected than distal joints. Patient demographics and stroke pathology factors
      were not associated with weakness, but stroke-related impairments were.

PMID- 16809215
TI  - The use of rhythmic auditory cues to influence gait in patients with Parkinson's
      disease, the differential effect for freezers and non-freezers, an explorative
      study.
AB  - PURPOSE: To study the effect of rhythmic auditory cues on gait in Parkinson's
      disease subjects with and without freezing and in controls. METHOD: A volunteer
      sample of 20 patients (10 freezers, 10 non-freezers) and 10 age-matched controls
      performed five randomized cued walking conditions in a gait-laboratory. Auditory
      cues were administered at baseline frequency, at an increased step frequency of
      10 and 20% above baseline and at a decreased step frequency of 10 and 20% below
      baseline. Mean step frequency, walking speed, stride length and double support
      duration were collected. RESULTS: Rhythmical auditory cueing induced speed
      changes in all subjects. Stride length was not influenced by rhythmical auditory
      cues in controls, whereas patients showed a larger stride length in the -10%
      condition (p < 0.01). Freezers and non-freezers showed the same response to
      rhythmical auditory cues. Within group analysis for stride length showed
      different cueing effects. Stride length decreased at the +10% condition for
      freezers (p < 0.05), whereas it increased for non-freezers. CONCLUSIONS: This
      study points to fact that physiotherapists might need to carefully adjust the
      cueing frequency to the needs of patients with and without freezing. On the basis
      of the present results we recommend to lower the frequency setting for freezers,
      whereas for non-freezers an increase of up to +10% may have potential therapeutic
      use.

PMID- 16809216
TI  - The role of the spiritual dimension of the self as the prime determinant of
      health.
AB  - PURPOSE: To present a clinical commentary on the relationship of spirituality to
      healthcare for those with chronic physical conditions. METHOD: A spiritually
      based theory of self-identity was presented, based on selected literature to
      identify the process of health attainment for those with chronic conditions. The
      resultant Health Change Process Theory was then discussed in relation to relevant
      empirical research and the implications for rehabilitation practice were
      outlined. RESULTS: The development of a resilient, intrinsic, spiritually based
      concept of self was found to be pivotal to health outcomes in rehabilitation.
      This was then incorporated within a Health Change Process Theory to explain and
      predict the course followed by people with chronic disorders to achieve health.
      CONCLUSION: The Health Change Process Theory provides an inclusive framework
      within which acute and chronic rehabilitation healthcare can be merged to
      maximise health outcomes. Nevertheless, a need remains to develop a quantitative
      measure of individual holistic health, based on this theory, to facilitate its
      use in rehabilitation practice. This paper forwards an explanation for the
      process that people experiencing chronic physical disabilities undergo as they
      achieve health. A concept of self that identifies the spiritual core as the
      component that determines the constancy and continuity of self as a whole which
      is necessary for health is presented as the basis of the rehabilitative health
      process.

PMID- 16809217
TI  - Exogenous surfactant restores lung function but not peripheral immunosuppression
      in ventilated surfactant-deficient rats.
AB  - The authors have previously shown that mechanical ventilation can result in
      increased pulmonary inflammation and suppressed peripheral leukocyte function. In
      the present study the effect of surfactant therapy on pulmonary inflammation and
      peripheral immune function in ventilated surfactant-deficient rats was assessed.
      Surfactant deficiency was induced by repeated lung lavage, treated rats with
      surfactant or left them untreated, and ventilated the rats during 2 hours.
      Nonventilated rats served as healthy control group. Expression of macrophage
      inflammatory protein (MIP)-2 was measured in bronchoalveolar lavage (BAL),
      interleukin (IL)-1beta, and heat shock protein 70 (HSP70) were measured in total
      lung homogenates. Outside the lung phytohemagglutinin (PHA)-induced lymphocyte
      proliferation, interferon (IFN)-gamma and IL-10 production, and natural killer
      activity were measured in splenocytes. After 2 hours of mechanical ventilation,
      expression of MIP-2, IL-1beta, and HSP70 increased significantly in the lungs of
      surfactant-deficient rats. Outside the lung, mitogen-induced proliferation and
      production of IFN-gamma and IL-10 reduced significantly. Only natural killer cell
      activity remained unaffected. Surfactant treatment significantly improved lung
      function, but could not prevent increased pulmonary expression of MIP-2, IL
      1beta, and HSP70 and decreased peripheral mitogen-induced lymphocyte
      proliferation and IFN-gamma and IL-10 production in vitro. In conclusion, 2 hours
      of mechanical ventilation resulted in increased lung inflammation and partial
      peripheral leukocyte suppression in surfactant-deficient rats. Surfactant therapy
      ameliorated lung function but could not prevent or restore peripheral
      immunosuppression. The authors postulate that peripheral immunosuppression may
      occur in ventilated surfactant deficient patients, which may enhance
      susceptibility for infections.

PMID- 16809218
TI  - Doxycycline decreases monocyte chemoattractant protein-1 in human lung epithelial
      cells.
AB  - Certain antibiotics possess anti-inflammatory properties and could potentially be
      used to treat inflammatory lung diseases associated with an influx of monocytes
      such as panbronchiolitis, asthma, cystic fibrosis, and bronchitis. Doxycycline is
      reported to possess anti-inflammatory effects. Monocyte chemoattractant protein-1
      (MCP-1) is a major inflammatory cytokine and a powerful chemoattractant for
      monocytes. The authors hypothesized that doxycycline exerts its anti-inflammatory
      effects, in part, by reducing MCP-1 production. To test this hypothesis, A549
      human lung epithelial cells were stimulated with cytomix in the presence or
      absence of doxycycline. In stimulated cells doxycycline decreased MCP-1
      production by 95% and in monocyte chemotaxis assays migration decreased by 55%.
      However, doxycycline did decrease expression of MCP-1 mRNA and did not effect its
      stability. These data demonstrate that doxycycline modulates MCP-1 production and
      suggest that doxycycline may provide a new anti-inflammatory therapy for chronic
      lung diseases.

PMID- 16809219
TI  - Interleukin-6 has no effect on surfactant or lung function in different lung
      insults.
AB  - The current study determined if interleukin-6 (IL-6) had a causative role in the
      lung dysfunction and/or surfactant alterations associated with three different
      lung insults. IL-6 (or saline) was instilled into rats followed by mechanical
      ventilation in vivo for 4 hours. Also, IL-6 (-/-) and wild-type mice were
      subjected to 3 insults: ex vivo injurious mechanical ventilation; cecal ligation
      and perforation; and hyperoxia exposure. In all experiments, the presence or
      absence of IL-6 did not significantly influence gas exchange, lung compliance, or
      various surfactant measurements. These results suggest that IL-6 may have a
      limited role in the surfactant alterations observed in acute lung injury.

PMID- 16809220
TI  - A Peptide with anti-transglutaminase activity decreases lipopolysaccharide
      induced lung inflammation in mice.
AB  - Octapeptide R2 (KVLDGQDP), which has anti-transglutaminas (TGase) activity,
      decreases inflammation in allergic conjunctivitis model in guinea pigs. The
      authors examined the effect of R2 on lipopolysaccharide (LPS)-induced lung injury
      in BALB/c mice. R2 inhalation significantly decreased neutrophil count and
      cytokine mRNA expression in the lungs of LPS (25 mg/kg)-treated mice (P < .05).
      It also showed a tendency for decreased tumor necrosis factor (TNF)-alpha
      immunoreactive protein in lung homogenates and significantly decreased TNF-alpha
      immunoreactive protein in the serum of LPS-injected mice (P < .05). These results
      indicate that TGase may be a new therapeutic target in LPS-induced lung
      inflammation.

PMID- 16809221
TI  - Noninvasive assessment of pulmonary emphysema using dynamic contrast-enhanced
      magnetic resonance imaging.
AB  - Emphysema tends to be complicated by diffuse abnormalities in the pulmonary
      peripheral microvasculature. The aim of this study was to evaluate whether
      dynamic contrast-enhanced magnetic resonance imaging (MRI) could provide a valid
      assessment of pulmonary blood flow as an indicator of the severity of emphysema.
      To do this, the authors compared MRI data with the pathological findings in lung
      tissue. Dynamic contrast-enhanced MRI is a noninvasive method and can be used to
      repeatedly monitor clinicopathological severity. Using MRI clear pulmonary
      vascular information can be obtained easily, and the relative pulmonary blood
      flow in the lung parenchyma can be quantified.

PMID- 16809222
TI  - Gratitude.

PMID- 16809223
TI  - Samuel D. Gross: the nestor of American surgery.
AB  - Samuel David Gross (1805-1884) represented the most notable surgeon of his
      generation and was honored with the title of "The Nestor of American Surgeon" by
      surgeon biographer Isaac Minis Hays. Of Pennsylvania Dutch stock, he was born on
      the family farm near Easton, Pennsylvania. He attended Wilkebarre Academy and
      Lawrenceville High School, noted private institutions of the day. He apprenticed
      under Doctor Joseph K. Swift of Easton and later with Professor George McClellan
      while in Philadelphia. In 1828, he graduated from Jefferson Medical College and
      remained for a short time in Philadelphia. Professor Gross focused his
      professional pursuits in the cities of Easton (1830-1833), Cincinnati (1833
      1840), Louisville (1840-1856), and Philadelphia (1856-1882). He retired from
      Jefferson Medical College two years before his death in 1884. Samuel D. Gross'
      contributions to surgery were numerous and diverse. He was recognized as a
      prolific author of classic texts of pathology, surgery, and history, an educator,
      a leader, a surgical researcher, and a pioneer surgeon practitioner. His
      influence in national affairs was immense, and his recognition as a respected
      surgeon was unmatched. He remains the most distinguished surgeon of his times.
      History values him as a hard working, honest, highly competent, and committed
      individual. His capacity for work and his dedication to a single cause were
      unrivaled. Doctor Gross integrated the best that surgery could give to future
      generations of surgical professionals.

PMID- 16809224
TI  - Interstitial cells of cajal in patients with constipation due to total colonic
      inertia.
AB  - Colonic wall contains interstitial cells of Cajal. In view of studies
      demonstrating that Cajal cells generate electric waves which are presumably
      responsible for colonic motor activity, and that these waves are absent in total
      colonic inertia, we investigated the hypothesis that colonic Cajal cells might be
      disordered in patients with total colonic inertia. The study comprised 28
      patients (age 41.6 +/- 8.2 SD years, 19 women, 9 men) with total colonic inertia
      in whom total colectomy was performed. Colonic specimens obtained from normal
      segments of the excised colon of 24 cancer patients acted as controls. Specimens
      were subjected to c-kit immunohistochemistry. Controls for antisera specificity
      consisted of tissue incubated with normal rabbit serum that had been substituted
      for the primary antiserum. C-kit-positive branched Cajal-like cells were detected
      in the musculature of the normal colonic segments. They were distinguishable from
      the C-kit-negative smooth muscle cells and the C-kit-positive but unbranched mast
      cells. No Cajal cells were detected in colon of total colonic inertia patients.
      The absence of Cajal cells in patients with total colonic inertia can be assumed
      to explain the absence of electric waves and motile activity previously reported
      in these patients. Further studies are needed to investigate the cause of Cajal
      cell absence.

PMID- 16809225
TI  - Analysis of the correlation of plasma NO and ET-1 levels in rats with acute
      mesenteric ischemia.
AB  - Mesenteric ischemia is a devastating disease process that frequently challenges
      clinicians. To enhance the early diagnosis of gut ischemia and judgment of its
      severity, it may be helpful to detect the unusual existence or increase in
      biomarkers in the body fluid. The aim of the present study was to evaluate the
      correlation of plasma nitric oxide (NO) and endothelin-1 (ET-1) levels to
      mesenteric ischemia using an animal model. Acute mesenteric ischemia (AMI) was
      produced experimentally by occlusion of the mesenteric vessels in the terminal
      ileum by the tenting of a thread. The determination of plasma NO and ET-1 levels
      were obtained before operation (T0, baseline value), and at 10 (T10), 20 (T20),
      30 (T30), and 60 (T60) min after the creation of AMI. Sham-operated rats served
      as controls. After 30 min of experiments, the plasma NO and ET-1 levels were
      significantly higher in the AMI group than in the control group (both p < .01).
      Both the plasma NO and ET-1 levels in AMI group increased significantly after 30
      min of ischemia (both p < .001 vs. respective baseline value), and they were 60%
      and 84% above the baseline value, respectively. In addition, ischemic intestinal
      injury was confirmed by the significantly elevated histological scores in the AMI
      group after 60 min of ischemia (p < .001). Our preliminary results suggest the
      possibility of important insights regarding NO and ET-1 changes into the
      mechanism of pathogenesis in AMI in rats. The increases in plasma NO and ET-1
      levels may potentially be noninvasive biomarkers for the early detection of this
      disease.

PMID- 16809226
TI  - Erythropoietin stimulates wound healing and angiogenesis in mice.
AB  - Erythropoietin exerts hematopoietic effects by stimulating proliferation of early
      erythroid precursors. Nonhematopoietic effects of erythropoietin have also been
      shown. It may act as a new angiogenic factor in wound healing. This study aimed
      to investigate the effect of systemic administration of recombinant human
      erythropoietin on wound healing in mice. Dorsal incisional wounds were performed
      in mice, which were then divided into two groups; a group treated for 7 days with
      recombinant human erythropoietin, and a control group. Sacrificing animals on day
      7, the wound tissues were collected for analysis of wound breaking strength,
      malondialdehyde, a marker of lipid peroxidation, hydroxyproline, an index of
      reparative collagen deposition, reduced glutathione levels, and for histological
      evaluation. The immunohistochemical determination of vascular endothelial growth
      factor (VEGF) which is believed to be the most prevalent angiogenic factor
      throughout the skin repair process, was also studied. The treatment significantly
      increased wound breaking strength by decreasing malondialdehyde and increasing
      hydroxyproline levels on day 7 after wounding. No statistically meaningful change
      was observed in reduced glutathione content. VEGF was immunostained significantly
      more on wound tissue of treated animals compared to the control group.
      Recombinant human erythropoietin treatment may be effective in wound healing due
      to inhibition of lipid peroxidation, deposition of collagen, and VEGF expression
      in wound area.

PMID- 16809227
TI  - Effect of N-acetylcysteine on blood and tissue lipid peroxidation in
      lipopolysaccharide-induced obstructive jaundice.
AB  - In obstructive jaundice, free radical production is increased and antioxidative
      activity is reduced. N-Acetylcysteine (NAC) has a beneficial effect with anti
      inflammatory and antioxidant activity, acting as a free radical scavenger. NAC
      inhibits inducible nitric oxide synthase, suppresses cytokine expression/release,
      and inhibits adhesion molecule expression and nuclear factor kappa B. The aim of
      this study was to investigate the effects of NAC on liver/renal tissue and serum
      lipid peroxidation in lipopolysaccharide (LPS)-induced obstructive jaundice. We
      randomized 60 rats into 6 groups: group 1, Sham; group 2, obstructive jaundice
      (OJ) induced after bile-duct ligation; group 3, OJ + NAC (100 mg kg- 1
      subcutaneously); group 4, OJ + LPS (10 mg kg-1); group 5, OJ + NAC + LPS; and
      group 6, OJ + LPS + NAC. For each group, the biochemical markers of lipid
      peroxidation and the antioxidant products were measured in serum and liver/renal
      tissue after sacrifice. Almost all lipid peroxidation products levels were
      increased and antioxidant products levels were decreased in groups who received
      LPS (groups 4, 5, and 6), but the effect was less remarkable when NAC was
      administered before LPS (group 5). The same trend was seen for groups with OJ +/-
      LPS who did not received NAC or received it after induced toxemia (groups 2, 4,
      and 6) as compared to groups 1 and 3. Moreover, in the case of OJ + LPS, rats
      treated with NAC before LPS (group 5) had lower lipid peroxidation products
      levels and higher antioxidant products levels as compared to those who did not
      received NAC (group 4). This phenomenon was not reproducible with NAC
      administered after LPS (group 6). Thus, results of this study showed that NAC
      prevents the deleterious effects of LPS in obstructive jaundice by reducing lipid
      peroxidation in serum and liver/renal tissue if administered before LPS.
      Nonetheless, NAC failed to prevent the lipid peroxidation in the case of
      established endotoxemia in obstructive jaundice.

PMID- 16809228
TI  - Tomographic comparison of ventilation techniques for CT-guided thoracoscopic
      staple excision of subcentimeter lung nodules.
AB  - This study was planned to compare the computed tomographic detectability of lung
      nodules in three ventilatory conditions: total lung capacity, high-frequency
      ventilation, and total lung deflation. In an ex vivo lung model, 44 nodules were
      simulated. Using computed tomography (CT) scans, nodules were detected and
      compared to the actual number and excised under CT guidance. Simulated nodules
      measured 6.2 +/- 2.1 mm and demonstrated an attenuation of 175 +/- 14 HU.
      Observer confidence was highest at total lung capacity (5.00 +/- 0.00), in
      comparison to high-frequency ventilation and total lung deflation (4.69 +/- 0.78,
      4.94 +/- 0.27, p = .24). The kappa score for total lung capacity, high-frequency
      ventilation, and total lung deflation was 1.00, 0.96, and 0.98, respectively,
      indicating a very high interrater reliability. Although surgical devices
      generated a substantial artifact, 90% of nodules were excised. Thus, although
      total lung capacity produces the highest confidence level, all three of the
      ventilatory techniques examined have similar detection of subcentimeter pulmonary
      nodules using computed tomography scans.

PMID- 16809229
TI  - A model of tissue-engineered ventral hernia repair.
AB  - We have developed a tissue-engineered ventral hernia repair system using our
      novel aligned collagen tube and autologous skeletal muscle satellite cells. In
      this model system, skeletal muscle satellite cells were isolated from a biopsy,
      expanded in culture, and incorporated into our collagen tube scaffold, forming
      the tissue-engineered construct. We characterized the results of the repaired
      hernias on both the gross and microscopic scales and compared them to an
      unrepaired control, an autologous muscle repair control, and a collagen-tube-only
      repair. Untreated animals developed a classic hernia sac, devoid of abdominal
      muscle and covered only with a thin layer of mesothelial tissue. Significant
      muscle, small-diameter blood vessels, and connective tissue were apparent in both
      the autologous control and the engineered muscle repairs. The engineered muscle
      repairs became cellularized, vascularized, and integrated with the native tissue,
      hence becoming a "living" repair. A tissue-engineered construct repair of ventral
      hernias with subsequent incorporation and vascularization could provide the
      ultimate in anterior wall myofascial defect repair and would further the
      understanding of striated muscle engineering. The knowledge gained from our model
      system would have immediate application to mangled extremities, maxillofacial
      reconstructions, and restorative procedures following tumor excision in other
      areas of the body.

PMID- 16809230
TI  - IdeR in mycobacteria: from target recognition to physiological function.
AB  - In mycobacteria, iron dependent transcription regulator (IdeR) regulates
      transcription of genes in response to iron levels. The IdeR regulated genes have
      been investigated mostly in M. tuberculosis, M. smegmatis, and in few of the
      other related species. Recent advances in crystal structure solution and
      computational as well as experimental identification of IdeR targets has provided
      insight into IdeR structure and function. Here in this review we take stock of
      current state of knowledge on IdeR and its targets to understand the underlying
      design of the IdeR regulon and its role in mycobacterial physiology.

PMID- 16809231
TI  - Environmental stress response in wine lactic acid bacteria: beyond Bacillus
      subtilis.
AB  - Lactic acid bacteria (LAB) constitute a heterogeneous group of bacteria that are
      traditionally used to produce fermented foods. The industrialization of food
      transformations has increased the economical importance of LAB, as they play a
      crucial role in the development of the organoleptic and hygienic quality of
      fermented products. However, the strains selected for industrial purposes, should
      tolerate adverse conditions encountered in industrial processes, either during
      starter handling and storage (freeze-drying, freezing, or spray-drying) or during
      food processing in which abiotic stresses such as heat, cold, acidity, and high
      concentration of NaCl or ethanol are common. Wine LAB have to deal with several
      stresses including an acidic pH, a high alcoholic content, non optimal growth
      temperatures, and growth-inhibitory compounds such as fatty acids and tannins,
      originated from yeast and bacteria metabolism. Wine LAB have developed several
      mechanisms to escape or to tolerate wine conditions. They carry out a malolactic
      fermentation in this stressful environment. In addition to the regulation of the
      expression of specific genes, bacteria have evolved adaptive networks to face the
      challenges of a changing environment and to survive under conditions of stress.
      The so called Global Regulatory Systems control the simultaneous expression of a
      large number of genes in response to a variety of environmental stress factors.
      CIRCE sequences able to bind the HrcA repressor, sigma(B) dependent promoters and
      CtsR regulatory elements have been observed in several genes identified from wine
      LAB. Improved knowledge of regulators and a better understanding of LAB stress
      responses could constitute a basis of comparison with the well known model
      microorganisms, Escherichia coli and Bacillus subtilis. Moreover, it can provide
      an important insight into improving current industrial starter strains.

PMID- 16809232
TI  - Unidirectional movement of flares of cells of Myxococcus xanthus.
AB  - Amongst other modes, Myxococcal cells move in swarms that are flares or columns
      of cells. It has been argued that this is a strategy allowing a large enough
      number of them to encounter food bacteria. Then, the combined large amount of
      extracellular lytic enzymes from the mass of cells can provide adequate nutrient
      resources from the food bacteria for all the myxococci of the swarm. However, how
      they move as a coherent column has not been adequately explained. Here based on
      the idea that a rare cell can experience a special mutation such that it moves
      only unidirectionally, a proposal to account for this aspect of Myxococcus cell
      movement is suggested. Although wild type individual organisms of this species
      engage in forward and back movements, a mutant cell that moves unidirectionally
      can bias the movement of associated wild type cells and lead to the formation of
      a column of cells, headed by such a unique mutated cell. The non-mutated cells
      follow along it is suggested because of the S-motility (or social motility)
      system. This may link them to this single unidirectionally moving mutant cell to
      give a coherent movement to the column. This proposed type of mutation back
      mutates to wild type and the column no longer functions as such and only wild
      type cells are present.

PMID- 16809233
TI  - Role of poly-galacturonase inhibiting protein in plant defense.
AB  - Polygalacturonase-inhibiting proteins (PGIPs) are plant proteins believed to play
      an important role in the defense against plant pathogen fungals. PGIPs are
      glycoproteins located in plant cell wall which reduce the hydrolytic activity of
      polygalacturonases (PGs), limit the growth of plant pathogens, and also elicit
      defense responses in plant. Furthermore, PGIPs belong to the super family of
      leucine reach repeat (LRR) proteins which also include the products of several
      plant resistance genes. Many of the studies show the PGIP properties, molecular
      characteristics, and PGIP gene expression induced by some elicitors. Some of the
      studies review individual PGIP gene expression in different signal transduction
      pathways. This article summarizes the properties, different signal transduction
      mechanisms, detecting methods, transgenic plants, and function of PGIP. It also
      presents PGIP gene expression in different stages of maturity, tissues, and
      varieties. The review especially reports the particular PGIP gene expression
      induced by different biotic and abiotic stresses, offers some questions, and
      prospects the future study, which are needed in order to develop efficient
      strategies for disease-resistant plants. They may be useful for genetic
      engineering to obtain transgenic plants with increased tolerance to fungal
      infection, which decrease the use of insecticide.

PMID- 16809236
TI  - Asthma, surgery, and general anesthesia: a review.
AB  - Over 20 million Americans are affected with asthma. Many will require some type
      of surgical procedure during which their asthma management should be optimized.
      Preoperative assessment of asthma should include a specialized history and
      physical as well as pulmonary function testing. In many asthmatic patients,
      treatment with systemic corticosteroids and bronchodilators is indicated to
      prevent the inflammation and bronchoconstriction associated with endotracheal
      intubation. The use of corticosteroids has not been shown to adversely affect
      wound healing or increase the rate of infections postoperatively. Preoperative
      systemic corticosteroids may be used safely in the majority of patients to
      decrease asthma-related morbidity.

PMID- 16809237
TI  - Health effects of ultraviolet irradiation in asthmatic children's homes.
AB  - OBJECTIVE: Centrally installed ultraviolet (UV) irradiation units were
      investigated to determine the potential health benefits in mold-sensitized
      asthmatic children. METHODS: Nineteen mold-sensitized asthmatic children 5 to 17
      years of age with home central ventilation systems were enrolled in a 28-week
      double-blinded placebo controlled cross-over trial. Clinical outcome measurements
      included morning and evening peak expiratory flow rates (PEFR), PEFR variability,
      change in forced expiratory volume in 1 second (FEV1), change in total
      rhinoconjunctivitis and asthma symptom scores, change in rhinoconjunctivitis and
      asthma quality-of-life scores, and total (rescue and controller) medication use
      from baseline and between time periods. Environmental outcomes included changes
      in temperature, relative humidity, dew point, and indoor airborne mold and
      bacterial counts from baseline and between time periods. Analysis of variance
      (ANOVA) and regression analysis and t test were used to evaluate relationships
      between environmental exposure(s) and clinical outcome measurements during each
      study period. RESULTS: Twelve male and seven female children, average age 10.6
      years, were enrolled. A statistically significant improvement in PEFR variability
      in subjects receiving CREON2000 units followed by placebo units was observed (p <
      0.05) across both treatment periods. Within group analysis during treatment
      period 1, a statistically significant improvement in reduction of asthma symptom
      scores, the number of days with asthma symptoms, total asthma medication use, and
      PEFR variability were observed in subjects receiving CREON2000 units versus
      placebo units (p < 0.05). No significant differences were observed between the
      CREON 2000 and placebo units for other clinical or environmental outcome
      measurements. CONCLUSIONS: Central UV irradiation was effective at reducing
      airway hyperresponsiveness manifested as PEFR variability and some clinical
      symptoms. A larger cohort controlled longitudinal study to validate the clinical
      health effects of UV irradiation as a primary indoor environmental intervention
      for allergic asthma is necessary to confirm this finding.

PMID- 16809238
TI  - Impact of a low-cost and simple intervention in enhancing treatment adherence in
      a Brazilian asthma sample.
AB  - The aim of this study was to evaluate adherence to treatment in persistent asthma
      in Brazil to determine the factors associated with non-adherence and to measure
      the efficacy of telephone calls in enhancing adherence. In a prospective,
      multicenter, interventional clinical trial with parallel groups, asthmatics were
      randomized into an intervention group or a control group. Asthmatics included in
      the intervention group received an initial telephone call to record demographic
      information and asthma characterization. After that, biweekly telephone calls
      were made to promote treatment adherence. Asthmatics included in the control
      group received only the initial and final telephone calls. Both groups received
      three packages of salmeterol/fluticasone for 3 months. The main outcome measure
      was the percentage of participants who took the prescribed doses of the drug. A
      total of 271 patients were included. The overall adherence rate was 51.9% for the
      control group and 74.3% for the intervention group. This meant a reduction of
      relative risk (RRR) of 47% (p < 0.001). The number needed to treat (NNT) was 4.5.
      The only variable associated with better adherence was severe persistent asthma.
      A low-cost easily implemented intervention, tailored to each individual, enhanced
      the adherence rate among Brazilian asthmatic patients.

PMID- 16809239
TI  - Role of vascular endothelial growth factor in pulmonary endothelial cell injury
      by exercise challenge in asthmatic patients.
AB  - This study was designed to examine the role of vascular endothelial growth factor
      (VEGF) in pulmonary endothelial cell injury by exercise in asthmatics. Post
      exercise circulating thrombomodulin (TM) levels were significantly increased in
      asthmatics. Moreover, the increase in TM levels with exercise was significantly
      correlated with VEGF level in induced sputum from asthmatics (r = 0.80, p =
      0.0007). After inhaled steroid therapy, post-exercise TM levels were
      significantly decreased, but the increase in TM levels with exercise was also
      correlated with VEGF level (r = 0.60, p = 0.01). Thus, pulmonary endothelial
      cells stimulated by VEGF in asthmatic airways may be sensitive to exercise
      challenge.

PMID- 16809240
TI  - Assessing the value of children's asthma camps.
AB  - The Consortium of Children's Asthma Camps Directors commissioned a study to
      determine the value of asthma camps. This study aimed to identify the
      opportunities and the Consortium's role in this future direction. A multi-method,
      retrospective study was conducted with the following findings: camper
      demographics; camps provide a unique experience; there is moderate to high level
      of published evidence regarding children's asthma camps; camps are managed by
      organizations with extensive experience and by minimal paid staff; and the
      components of asthma education are fairly consistent across camps, while the
      duration of education, curricula used, and use of asthma action plans are not.

PMID- 16809241
TI  - Associations of acculturation and country of birth with asthma and wheezing in
      Mexican American youths.
AB  - BACKGROUND: Mexican Americans have lower rates of asthma than other ethnic groups
      in the United States. OBJECTIVE: To examine the relationship between country of
      birth and acculturation with asthma and wheezing among Mexican American youths.
      METHODS: We used Chi-squared statistics and logistic regression analyses to
      determine the associations of country of birth and acculturation with asthma and
      wheezing among 1,770 Mexican Americans age 12-19 years who participated in the
      National Health and Nutrition Examination Survey 1999-2002. RESULTS: Mexican
      American adolescents born in the United States and those with high acculturation
      levels reported significantly higher prevalence rates of asthma, wheezing, and
      hay fever than their peers with low acculturation levels and born in Mexico. In
      multivariate analyses, youths with a high acculturation level had a higher risk
      of asthma than those with a low acculturation level independent of country of
      birth. Highly acculturated youths born in the US had a higher risk for wheezing
      compared with less acculturated US-born or Mexico-born participants after
      adjusting for confounding variables. In contrast, associations of asthma and
      wheezing with country of birth were not significant after controlling for
      acculturation. CONCLUSIONS. Our findings showed that both acculturation and
      country of birth were linked with the risk of asthma and wheezing, with
      acculturation having stronger effects than country of birth, among Mexican
      American youths. These findings may imply that factors modified by immigration
      and acculturation could influence the risk of asthma and wheezing. Identification
      of such factors could help in the design of asthma prevention programs.

PMID- 16809242
TI  - Seasonality in adult asthma admissions, air pollutant levels, and climate: a
      population-based study.
AB  - OBJECTIVE AND BACKGROUND: Most studies of asthma seasonal variations have not
      examined associations of environmental risk factors and climatic changes
      associated with seasonality in asthma hospitalizations. This study used
      population-based data to examine seasonality in asthma admissions and the
      associated seasonality in levels of air pollutants and climatic factors during a
      4-year period in Taiwan. METHODS: A total of 126,671 asthma hospitalizations in
      Taiwan during 1998-2001 operationalized as monthly admissions per 100,000
      population and monthly mean levels of criterion air pollutants and meteorological
      factors were subjected to Auto-Regressive Integrated Moving Average to test for
      seasonality and association between asthma admission rates and the pollutant and
      climatic factor levels. Owing to significant differences in seasonality between
      pediatric and adult age groups, this study was limited to 99,591 adult asthma
      cases to examine the seasonality issue as related to the criterion air pollutants
      and climatic factors using Spearman rank correlations. RESULTS: Seasonal trends
      showed a hospitalization peak in January through March and a sharp decline
      beginning in April to a trough in June for both sexes. Seasonal variations in
      adult asthma admissions were significantly positively correlated with levels of
      PM10, SO2, CO, NO2, and atmospheric pressure and negatively correlated with
      temperature and hours of sunshine. CONCLUSIONS: Adult asthma hospitalization
      propensity is highest in spring and is significantly correlated with air
      pollution and climate. Air quality control programs and early public warning
      systems on pollution and atmospheric factors are needed to enable predisposed
      individuals and their physicians to preempt attacks through primary and secondary
      preventive measures.

PMID- 16809243
TI  - Is fetal gender associated with emergency department visits for asthma during
      pregnancy?
AB  - BACKGROUND: To investigate if fetal gender (1) affects the risk of having an
      emergency department (ED) visit for asthma; and (2) is associated with adverse
      pregnancy outcomes among women who had at least one visit to the ED for asthma
      during pregnancy. METHODS: We linked two provincial administrative databases
      containing records on in-patient deliveries and ED visits. The study sample
      included women who delivered a live singleton baby between April 2003 and March
      2004. Pregnant women who made at least one ED visit for asthma were counted as
      cases and the rest of the women as control subjects. We performed a multivariable
      analysis using logistic regression to model the risk of having an ED visit for
      asthma, with fetal gender being one of the predictors. In addition, a series of
      multivariable logistic regressions were also constructed separately for cases and
      controls for the following adverse delivery outcomes: low birth weight baby,
      preterm delivery, and delivery via Caesarian section. RESULTS: Among 109,173 live
      singleton deliveries, 530 women had visited ED due to asthma during pregnancy.
      While having an ED visit for asthma was positively associated with teenage
      pregnancy, low income, and presence of pregnancy-induced hypertension, it was not
      associated with fetal gender (OR 1.01, 95% CI 0.85-1.19). Fetal gender was not a
      significant predictor of adverse pregnancy outcomes among women who had an asthma
      ED visit during pregnancy. CONCLUSION: Fetal gender does not affect the risk of
      having an ED visit for asthma during pregnancy, and it is not associated with
      adverse pregnancy outcomes among women who had an asthma-related ED during
      pregnancy.

PMID- 16809244
TI  - Looking beyond urban/rural differences: emergency department utilization by
      asthmatic children.
AB  - Asthma causes pediatric morbidity throughout the US with substantial regional
      variability. Emergency department (ED) utilization data were studied to determine
      if geographic variability of pediatric asthma cases exists within a state.
      Records for non-neonatal Maryland children less than 18 years of age seen and
      discharged from Maryland EDs from April 1997 through March 2001 were analyzed.
      While Baltimore City had the highest rates of asthma visits, adjusted odds ratios
      identified the wealthiest suburban county to have a higher risk of an asthma ED
      visit. Children from rural counties, for the most part, had fewer ED asthma
      visits than children from urban and suburban counties.

PMID- 16809245
TI  - The effects of asthma on dental and facial deformities.
AB  - OBJECTIVE: The purpose of the study was to observe facial and teeth alterations
      in adult patients with asthma as opposed to a group who suffered from
      hypertension. METHODS: All patients included in this cross-sectional
      observational study were interviewed to obtain clinical data. Patients also
      followed an orthodontic assessment using model-facial photographic and gypsum
      casts to diagnose malocclusion and dentofacial deformities. Asthmatic patients
      were divided in two groups according to asthma onset under or over 14 years of
      age. RESULTS: A total of 61 asthmatics and 53 hypertensive patients were
      evaluated. Dental midline symmetry was significantly lower in asthmatics than in
      the hypertensive group (p = 0.006), whereas incompetent lip posture and open
      nasal lip angle were significantly more frequent in the asthmatic group than in
      the control group (p = 0.007 and 0.016, respectively). Asthmatics had more dental
      crossbite (p = 0.004), overbite (p = 0.01), overjet (p = 0.01), smaller inter
      bicuspids distance (p = 0.0009) and inter molar distance (p = 0.0001) than the
      control group. More crowding than diastems was observed in asthmatic patients. An
      association between the crossbite (p = 0.02) and maxillary crowding (p = 0.03)
      was also observed with the earlier age of asthma onset. CONCLUSION: The findings
      of this study lead us to note that dentofacial anomalies are related to asthma.

PMID- 16809246
TI  - Evaluation of a pediatric asthma awareness program.
AB  - OBJECTIVE: To evaluate knowledge and attitudinal outcomes of an educational
      asthma program for third-grade children with and without asthma. METHODOLOGY:
      "The Lion Who Couldn't Roar" was presented to third-grade classes in three
      Chicago area Counties. Participant asthma knowledge and attitudes were assessed
      via a print-based pretest-posttest design. Teacher satisfaction was also
      assessed. Data were analyzed using Rasch analysis before paired t tests were
      performed. RESULTS: Pre- and post-assessments were completed by 943 participants.
      A statistically significant increase in mean logit scores was identified on both
      knowledge and attitude evaluations (p < 0.001, p < 0.001). CONCLUSIONS: The
      results provide evidence of program impact.

PMID- 16809248
TI  - A methodology to validate a structured diagnostic method used to diagnose female
      sexual dysfunction and its subtypes in postmenopausal women.

PMID- 16809249
TI  - A cognitive-behavioral group program for women with vulvar vestibulitis syndrome
      (VVS): factors associated with treatment success.
AB  - The results of this prospective open clinical trial (N = 76) indicate that a
      cognitive-behavioral group program for women with vulvar vestibulitis syndrome
      (VVS) affects sexuality, pain control, vaginal muscle control, and vestibular
      pain and that these changes may mediate changes in pain during intercourse.
      Improvements in sexual functioning and vestibular pain during treatment seem to
      be particularly important factors in determining short and longer term treatment
      outcome. These findings are consistent with a cognitive-behavioral
      conceptualization of VVS.

PMID- 16809250
TI  - Psychological and interpersonal correlates in men with erectile dysfunction and
      their partners: a pilot study of treatment outcome with sildenafil.
AB  - The role of psychological and interpersonal factors in the treatment of erectile
      dysfunction (ED) with sildenafil or other oral therapies has not been
      sufficiently investigated. We conducted a pilot study of psychosocial predictors
      of pharmacotherapy treatment outcome and satisfaction in men with ED and their
      partners. Sixty-nine men with mild to moderate ED and their partners were
      enrolled in a multicenter, open-label, treatment trial with sildenafil. Treatment
      measures included a battery of validated self-report measures and questionnaires.
      Subjects also were interviewed according to a semistructured interview protocol.
      Partner assessments included self-report measures of sexual function, mood, and
      relationship satisfaction. Results indicated that, prior to treatment, patients
      had erectile function scores in the range of mild to moderate ED, with relatively
      low levels of concomitant depression, anxiety, and psychological stress and high
      overall levels of relationship adjustment. Partner sexual function was in the
      normal range of total Brief Index of Sexual Functioning for Women (BISF-W;
      Taylor, Rosen, Leiblum, 1994) scores, although more than one third of female
      partners had specific sexual complaints or problems. Among couples who completed
      one or both follow-up visits (N = 34), sildenafil treatment resulted in
      significant improvements in all aspects of sexual function in men, including
      sexual desire, orgasmic function, erectile function and overall sexual
      satisfaction. Significant improvements also were noted in partners' ratings of
      sexual function in most domains, including arousal, pleasure, and orgasm. Higher
      baseline levels of sex-specific anxiety were negatively associated with
      improvement in erections following treatment. Relationship adjustment at
      baseline, contrary to expectations, did not predict erectile or sexual
      satisfaction following treatment in the men or their partners but was
      significantly correlated with changes in sexual desire. Baseline levels of
      depression, anxiety, and stress generally were unrelated to efficacy or treatment
      satisfaction. However, we observed a curvilinear relationship in the men between
      baseline levels of stress and treatment discontinuation (i.e., subjects with
      moderate levels of stress were less likely to discontinue treatment). Because of
      a high number of dropouts, results of this pilot study await confirmation in a
      larger and more adequately powered clinical trial.

PMID- 16809251
TI  - Sexual dysfunction and chronic illness: the role of flexibility in coping.
AB  - Sexual dysfunction is common among individuals with chronic illnesses and is
      associated with distress and reduced quality of life. Because of the long-term,
      often irreversible nature of sexual dysfunction in chronic illness and
      limitations of pharmacological treatments, there is a need to understand
      cognitive and behavioral coping processes in this population. We present a model
      of coping with sexual dysfunction that focuses on the construct of flexibility,
      including the definition of sexual functioning and its centrality to overall self
      concept. We describe how this model can be applied in a comprehensive approach to
      treating sexual dysfunction in individuals with chronic illnesses.

PMID- 16809252
TI  - Use of the female sexual function index in women with vulvar intraepithelial
      neoplasia.
AB  - The present investigation extends the validation of the Female Sexual Function
      Index (FSFI; Rosen et al., 2000) to include women with vulvar excisions for
      vulvar intraepithelial neoplasia (VIN). No instrument previously has been
      validated in this population. We administered the instrument to 43 women (n = 43)
      with VIN treated with vulvar excision and age-matched healthy controls (n = 43).
      We found the FSFI to have high reliability and validity in the VIN excision
      population. Discriminant validity and internal consistency were within acceptable
      ranges. Using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire Core 30 (EORTC QLQ C-30; Agronson et al., 1993) and
      the FSFI in this population, we found a correlation between a related construct
      of quality of life and sexual function.

PMID- 16809253
TI  - The sexual effects of testosterone replacement in depressed men: randomized,
      placebo-controlled clinical trial.
AB  - Symptoms of male hypogonadism such as low libido and erectile dysfunction (ED)
      respond to testosterone (T) replacement. In hypogonadal men with major depressive
      disorder (MDD), the extent to which T replacement alleviates sexual symptoms of
      hypogonadism is not known. We conducted 6 week double-blind placebo-controlled
      clinical trial in men with low and low-normal T levels (i.e., total T <or= 350
      ng/dl) and MDD. Men were randomized to receive weekly intramuscular injections of
      either T enanthate 200 mg or sesame-seed oil (placebo). The primary outcome
      measure was self-reported sexual functioning. We randomized 30 patients. The mean
      age was 52(SD +/- 8) years, mean T level 262.5(SD +/- 8) ng/dl, and mean baseline
      Hamilton Rating Scale for Depression (HAM-D) score 21(SD +/- 8). At baseline,
      sexual function was low, with the majority reporting having had normal erectile
      and orgasmic functioning 0-1 time in the preceding month. All patients who
      received T achieved normalization of their T levels. The HAM-D scores decreased
      significantly in both T and placebo groups, and there were no significant between
      group differences: reduction in mean HAM-D score from baseline to endpoint was
      10.1 in patients who received T and 10.5 in those who received placebo. Self
      reported sexual functioning improved slightly in both groups; a between-group
      difference was not detected. Both T replacement and placebo were associated with
      improvement in sexual function and mood, but differences between T and placebo
      were not distinguishable.

PMID- 16809257
TI  - Influence of hypercalcic and/or hyperoxalic diet on calcium oxalate renal stone
      formation in rats.
AB  - OBJECTIVE: To test whether increasing dietary calcium intake prevents calcium
      oxalate stone formation when the diet is oxalate-rich. Material and methods. Four
      groups, eight rats in each, were subjected to a lithogenic diet by the addition
      of 0.5% ethylene glycol to drinking water for 3 weeks. The first group, used as a
      control, simultaneously received a standard diet. The second group was
      supplemented with calcium at 500 mg/100 g of diet and the third group with
      oxalate at 3 g/100 g of diet. The diet given to the last group was supplemented
      with similar doses of calcium and oxalate. One day before the end of treatment,
      each animal was placed in a metabolic cage to collect 24-h urine samples and
      determine urinary parameters. The kidneys were removed to determine calcium
      oxalate deposits and for histological examination. RESULTS: The number of calcium
      oxalate crystals in renal tissue was highest in the oxalate group and calcium
      oxalate deposits were also found to be elevated in this group. Hyperoxaluria and
      hypocitraturia, induced by a oxalate-rich diet, seemed to be the major causes
      contributing to aggravated renal stone formation. The protective effect of
      dietary calcium supplementation, which was clear in the calcium + oxalate group,
      was probably due to intestinal binding of oxalate by calcium, thereby reducing
      urinary oxalate excretion. CONCLUSION: Increased dietary calcium intake can
      prevent calcium oxalate stone formation only when the diet is oxalate-rich.

PMID- 16809258
TI  - Oral oxycodone hydrochloride versus epidural anaesthesia for pain control after
      radical retropubic prostatectomy.
AB  - OBJECTIVE: To evaluate whether combined oral intake of paracetamol (4 x 1 g) +
      oxycodone hydrochloride (2x10 mg) is adequate and equivalent to epidural
      anaesthesia (EDA) with respect to postoperative pain control and postoperative
      mobilization after radical retropubic prostatectomy (RRP). MATERIAL AND METHODS:
      Forty consecutive patients scheduled for RRP were randomized to either: EDA with
      ropivacaine + paracetamol (4 x 1 g tablet) + injected or oral morphine on demand
      (EDA group); or infiltration of 25-40 ml of 0.25% bupivacaine into the wound +
      oxycodone hydrochloride (2 x 10 mg tablet) + paracetamol (4x1 g tablet) +
      injected or oral morphine on demand (OXY group). The groups were compared with
      respect to pain control determined by means of a visual analogue scale (VAS),
      time to free mobilization, hospital stay, complications, operation time and
      bleeding. RESULTS: Both analgesic regimens provided satisfactory analgesia, i.e.
      VAS scores remained significantly below 4 (p<0.0001). The EDA group experienced
      slightly less pain than the OXY group on the operation day but this was not
      significant: median VAS scores of 0.7 and 1.8, respectively (p=0.27). Median VAS
      scores during hospital stay were 1.7 in both treatment groups. VAS scores ranged
      from 0.1 to 3.3 and from 0.2 to 3.5 in the EDA and OXY groups, respectively.
      There was no significant difference in postoperative mobilization between the
      groups (p=0.06). The median duration of hospital stay was 3 nights in both
      groups. CONCLUSION: Postoperative pain control after RRP with oral oxycodone
      hydrochloride, paracetamol and extra morphine on demand is preferable to EDA when
      pain control as well as mobilization and costs are taken into account.

PMID- 16809259
TI  - Individual variation of hormonal recovery after cessation of luteinizing hormone
      releasing hormone agonist therapy in men receiving long-term medical castration
      therapy for prostate cancer.
AB  - OBJECTIVE: To evaluate the process of hormonal recovery after cessation of
      luteinizing hormone-releasing hormone (LHRH) agonist treatment in patients who
      had received long-term LHRH agonist therapy for prostate cancer. MATERIAL AND
      METHODS: Men who had successfully undergone androgen deprivation therapy with
      only monthly LHRH agonist therapy for > 30 months were enrolled and the
      administration of LHRH agonist was discontinued. Serum total testosterone,
      luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prostate
      specific antigen (PSA) were measured before the cessation of LHRH agonist therapy
      and every 4 weeks thereafter, and the administration of LHRH agonist remained
      suspended until the total testosterone level recovered to > 50 ng/dl. RESULTS:
      Ten patients were enrolled in the study. The median (range) castration period and
      the levels of serum LH, FSH, total testosterone and PSA at cessation of therapy
      were 39 (30-56) months,<0.5 (<0.5-1.8) mIU/ml, 6.4 (3.0-15.9) mIU/ml, 15.3 (5.8
      34.7) ng/dl and 0.13 (0.02-0.89) ng/ml, respectively. Testosterone recovered to >
      50 ng/dl in all cases. There were large variations in the times required for
      recovery of LH and FSH (30-100 days) and serum testosterone (30-330 days). PSA
      began to increase at various testosterone levels, and there was a large variation
      (0-83%; median 41%) in the ratio of the androgen suppression (testosterone < 50
      ng/dl) time to the period of LHRH agonist cessation. CONCLUSIONS: There was
      considerable variation in the hypothalamus-pituitary-testicular hormone profiles
      during recovery from long-term medical castration. These findings are noteworthy
      when interruption of androgen deprivation therapy is applied with the intention
      of delaying the progression of hormone-refractory cancer or improving the
      patient's quality of life.

PMID- 16809260
TI  - Sentinel node procedure in low-stage/low-grade penile carcinomas.
AB  - OBJECTIVE: To optimize the indication for sentinel lymph node (SLN) biopsy
      according to tumour size in penile carcinoma. MATERIAL AND METHODS: This was a
      retrospective analysis of 23 consecutive patients (median age 65 years; range 49
      85 years) with primary penile carcinoma classified according to the TNM
      classification as stage T1-T3 who were identified as having SLNs in the groins.
      SLNs were detected by means of preoperative injection of a 99mTc nanocolloid
      around the tumour and peroperative use of a gamma detector probe. The average
      tumour size was 2.9+/-1.3 cm. RESULTS: In 7/25 patients with penile carcinoma
      examined with the SLN method, metastases to inguinal lymph nodes could be
      demonstrated. Two out of three patients with primary penile carcinomas classified
      as T1 according to the TNM classification and tumours > 3 cm in diameter had
      inguinal lymph node metastases. One of the patients had a micrometastasis, which
      was detected by means of immunohistochemical analysis. Seven out of eight
      patients with penile carcinomas > 3 cm in diameter had lymph node metastases. We
      did not observe any major surgical complications associated with the SLN
      procedure. CONCLUSION: These data indicate that penile carcinomas with a diameter
      of >3 cm should be investigated with SLN biopsy regardless of stage. However,
      multicentre studies are needed in order to obtain the appropriate number of
      patients.

PMID- 16809261
TI  - Is carbon dioxide laser treatment of lichen sclerosus effective in the long run?
AB  - OBJECTIVE: To evaluate the long-term results after carbon dioxide laser treatment
      of lichen sclerosus. MATERIAL AND METHODS: We evaluated 62 consecutive patients
      with histologically verified lichen sclerosus admitted between 1985 and 1991. All
      patients were treated with a carbon dioxide laser with an output of 15-20 W and a
      defocused beam. This treatment vaporized the macroscopically altered area of the
      glans penis. Phimosis and superficial meatal stenosis were treated at the same
      session. Fifty-three men were still alive in 2004, and we were able to contact 50
      of them (94%). The patients were asked about recurrence of symptoms, any visible
      penile lesion and recurrence of meatal stenosis. All patients who reported
      symptoms were invited to visit the outpatient clinic for further examination.
      RESULTS: The median follow-up time was 14 years. At follow-up, 40 patients (80%)
      had no local symptoms and no visible lesion. Ten patients had minor symptoms but
      only two required further treatment. CONCLUSION: Long-term follow-up of carbon
      dioxide laser treatment of lichen sclerosus shows that the treatment is safe and
      gives good results.

PMID- 16809262
TI  - Prevalence of testicular microlithiasis in an asymptomatic population.
AB  - OBJECTIVE: Testicular microlithiasis is a rare, usually asymptomatic, finding of
      the testes associated with various genetic anomalies and infertility. It is also
      widely believed that testicular microlithiasis is strongly associated with
      testicular tumor. The aim of this prospective study was to determine the true
      prevalence of testicular microlithiasis in an asymptomatic population by means of
      ultrasound screening. MATERIAL AND METHODS: Healthy male volunteers (17-42 years
      old) were recruited from the annual Army Reserve Officer Training Corps training
      camp at Manisa, Turkey. A screening genitourinary history was obtained and a
      physical examination and screening scrotal ultrasound scan were performed.
      RESULTS: All men diagnosed with testicular microlithiasis underwent complete
      clinical evaluations, physical examinations and determination of tumor markers.
      Fifty-three men with testicular microlithiasis were identified from the 2179
      ultrasound scans, giving a prevalence of testicular microlithiasis of 2.4% in
      this asymptomatic population. The age (mean+/-SD) of subjects with testicular
      microlithiasis was 23.9+/-4.2 years (range 20-31 years). CONCLUSION: Our results
      suggest that there is no significant association between TM and testicular
      cancer, although it is difficult to rule out such an association without further
      studies with a longer follow-up period.

PMID- 16809263
TI  - Epidemiology of kidney stones in Iceland: a population-based study.
AB  - OBJECTIVE: The prevalence of kidney stones varies greatly between ethnic groups
      and geographic locations, ranging from 8% to 19% in males and from 3% to 5% in
      females in Western countries. The aim of this study was to examine the
      epidemiology of kidney stones in Iceland. MATERIAL AND METHODS: Data were derived
      from the Reykjavik Study, a population-based cohort study carried out between
      1967 and 1991. All subjects answered a thorough questionnaire concerning their
      medical history at each visit. The lifetime prevalence of kidney stones was
      calculated based on the answer to the question "Have you ever been diagnosed with
      a kidney stone?" at each person's first visit. Incidence was calculated based on
      answers from subjects who had made two or more visits. Prevalence and incidence
      were age-standardized to the truncated world population. Family history of kidney
      stones was also evaluated. RESULTS: A total of 9039 men aged 33-80 years and 9619
      women aged 33-81 years participated. Of these, 423 males and 307 females had a
      history of kidney stones (p=0.001). Prevalence increased significantly with age
      for both genders. Men aged 30-34 years had a prevalence of 2.9%, compared to 8.8%
      for those aged 65-69 years, whereas corresponding values for women were 2.5% and
      5.0%. The age-standardized prevalence for the 30-79 years age group was 4.3% for
      men and 3.0% for women. No significant increase in prevalence was observed over
      time. The incidence was 562 per 100 000 per year among men and increased
      significantly with age. The incidence among women was 197 per 100 000 per year
      and did not differ between age groups. A family history of nephrolithiasis was
      present in 25% of subjects with a history of kidney stones, and in 4% of those
      without. CONCLUSIONS: The incidence and prevalence of kidney stones in Icelandic
      women are similar to those that have been reported in other Western countries.
      The prevalence among men is lower that in neighboring countries but the incidence
      is similar. A strong family history of kidney stones suggests a genetic
      predisposition.

PMID- 16809264
TI  - Bladder exstrophy-epispadias complex: Investigation of suppressor of variegation,
      enhancer of zeste and Trithorax (SET) as a candidate gene in a large cohort of
      patients.
AB  - OBJECTIVE: The bladder exstrophy-epispadias complex (BEEC) describes a rare
      anterior midline defect with variable expression involving the infra-umbilical
      abdominal wall, including the pelvis, urinary tract and external genitalia. It is
      assumed that the underlying cause of BEEC is a multifactorial mode of
      inheritance; however, its aetiology remains unknown. Only a few BEEC patients
      with distinctive cytogenetic features such as numeric or structural chromosomal
      abnormalities have been reported. The observation of translocations concerning
      the region of chromosome 9q32-q34.1 in two patients implies that this region
      bears a candidate gene which, during early blastogenesis, governs the development
      of this primary field. In this context, we considered the suppressor of
      variegation, enhancer of zeste and Trithorax (SET) gene, located at chromosome
      9q34, to be a good candidate, as the protein encoded is involved in the
      regulation of cell proliferation and differentiation. Moreover, SET expression
      was detected in embryonic kidney. MATERIAL AND METHODS: A total of 33 patients
      affected with BEEC were analysed for mutations in the SET gene. RESULTS: SET
      analysis did not reveal either a mutation or the presence of four single
      nucleotide polymorphisms (dbSNP124) already described in the database.
      CONCLUSIONS: The data obtained in this study most likely exclude the SET gene as
      a possible genetic cause of BEEC. Hence, other genes in this region may
      contribute to the development of this midline defect.

PMID- 16809265
TI  - Urological trauma after gynecological and obstetric surgeries.
AB  - OBJECTIVE: Gynecological and obstetric surgeries are not uncommon causes of
      iatrogenic injury of the urinary tract. Herein, we retrospectively report our
      experience with these injuries over the last 18 years. MATERIAL AND METHODS:
      Between 1985 and 2003, 120 females (mean age 34.2+/-13.7 years) were included in
      this study. The types of injury were as follows: vesicovaginal fistula, n=90;
      ureterovaginal fistula, n=14, ureteric ligation, n=13, vesicouterine fistula,
      n=2; and ureterouterine fistula, n=1. Definitive repair of such injuries was
      performed in all cases, including 10 cases of recurrent vesicovaginal fistulae
      which were treated by means of augmentation cystoplasty or urinary diversion. All
      patients were evaluated regarding the time and type of surgical intervention and
      early and late postoperative complications, including failure of primary repair.
      RESULTS: Of the 80 cases of vesicovaginal fistulae treated with definitive
      repair, 12 (13.3%) showed recurrence of the fistula. Early ureteric deligation
      and early or delayed ureteroneocystostomy or ureteric replacement were successful
      in all cases with ureteric injury. There was no loss of kidney function following
      the trauma or its repair. CONCLUSIONS: It is mandatory for gynecologists and
      obstetricians to pay careful attention to the anatomy of the urinary tract in
      order to avoid its iatrogenic injury. Endourologic means were successful in
      enabling first aid management of some of these injuries. Early exploration is
      indicated in cases of ureteric obstruction that present early after trauma.
      Augmentation cystoplasty, urinary diversion or ileal replacement are indicated in
      only a few cases.

PMID- 16809266
TI  - Uroflowmetry with simultaneous electromyography versus voiding video
      cystourethrography.
AB  - OBJECTIVES: Urethral dysfunction may lead to a deterioration of kidney function
      and be life-threatening. A thorough diagnosis of the pathophysiology is
      consequently vital to ensure the correct treatment is given. MATERIAL AND
      METHODS: In this study, 34 adult patients suspected of a urethral etiology giving
      rise to urinary retention, urgency or chronic lower urinary tract infections were
      investigated by uroflowmetry with simultaneous electromyography and voiding video
      cystourethrography. CONCLUSIONS: Both methods proved to be essential for an
      accurate assessment of the pathological state.

PMID- 16809267
TI  - Preliminary data on monosymptomatic nocturnal enuresis in children and
      adolescents with type 1 diabetes.
AB  - OBJECTIVE: To evaluate the prevalence of monosymptomatic nocturnal enuresis (MNE)
      in a group of children and adolescents prior to the onset of type 1 diabetes
      (Dt1). MATERIAL AND METHODS: We considered 88 patients with Dt1 with a mean age
      of 15.2 years over a period of 3 years. All patients were investigated by means
      of a questionnaire about the occurrence of MNE prior to the onset of Dt1. Each
      patient had normal urinalysis results, with no glycosuria, a normal urinary flow
      rate and no day-time symptoms such as urge incontinence or urgency. RESULTS: We
      found that 24/88 patients (27.2%) were bedwetters before the onset of Dt1. After
      beginning insulin treatment, 7/24 bedwetters (29.2%) kept presenting MNE. In
      total, 7 of the initial 88 patients (7.9%) displayed persistent features of MNE.
      CONCLUSIONS: The occurrence of MNE may overlap with symptoms of Dt1 but requires
      specific medical attention as a separate entity due to its possible persistence
      even when Dt1 has been controlled by insulin treatment.

PMID- 16809268
TI  - Effects of erythropoietin treatment on cell-mediated immune responses in
      predialysis patients.
AB  - OBJECTIVE: The effects of erythropoietin (EPO) treatment on the immune functions
      of dialysis patients have been shown to be controversial and there are only
      limited data concerning predialysis patients. MATERIAL AND METHODS: Twenty-four
      predialysis patients with renal anemia were assigned to subcutaneous EPO
      treatment, and those in need (n=19) were additionally treated with i.v. iron
      every other week. We analyzed the effect of the start of EPO treatment on (i)
      lymphocyte and lymphocyte subclass counts, (ii) lymphocyte stimulation functions
      and (iii) persisting IgG-class antibody levels to the viral antigens of Epstein
      Barr virus and cytomegalovirus. RESULTS: Our main findings were a decrease in the
      absolute lymphocyte count, combined with decreases in all the main lymphocyte
      subclass counts. The absolute number of cells with activation and memory markers
      remained constant, and therefore their proportion slightly increased. The
      proliferation responses to phytohemagglutinin, tuberculin and tetanus declined
      significantly, while the amount of IgG-class viral antibodies remained unchanged,
      meaning that the humoral side of immunity was not affected by the start of the
      EPO treatment. Similarly, the proliferation response to pokeweed mitogen, a B
      cell mitogen, was unchanged. CONCLUSIONS: EPO treatment has a suppressive effect
      on cellular immune functions of predialysis patients. This suppression does not
      correlate with erythropoiesis, kidney function or iron status.

PMID- 16809269
TI  - Long-term graft and patient survival following renal transplantation in diabetic
      patients.
AB  - OBJECTIVE: To study long-term graft and patient survival following renal
      transplantation in diabetic and non-diabetic patients. MATERIAL AND METHODS: Over
      the time period 1985-99, 498 transplantations in 399 non-diabetic patients and 68
      transplantations in 62 diabetic patients were performed. The groups were similar
      with respect to age and sex. RESULTS: The patient survival rates (diabetic versus
      non-diabetic patients) were 88% vs 91% (p=NS) at 1 year, 68% vs 73% (p=NS) at 5
      years and 31% vs 52% (p<0.05) at 10 years. The graft survival rates (diabetic
      versus non-diabetic patients) were 72% vs 72% at 1 year, 52% vs 52% at 5 years
      and 27% vs 33% (p=NS) at 10 years. In the diabetic patients, mean haemoglobin
      (Hb)A1c 2 years before and 2 years after the transplantation was 7.5+/-1.4 vs
      8.2+/-1.6 mmol/l (p<0.05) and the mean blood pressure was 112+/-12 vs 107+/-9
      mmHg (p<0.05). Of the diabetic patients, 55% were smokers. Among the diabetic
      patients, graft and patient survival were independent of smoking habits, blood
      pressure, HbA1c and total cholesterol. CONCLUSIONS: Graft survival was similar in
      diabetic and non-diabetic patients. For the first 5 years following renal
      transplantation, the patient survival rates in the two groups were similar.
      Thereafter, survival among diabetic patients was poor. Mean HbA1c was relatively
      high, especially after the transplantation, and this may have contributed to the
      more rapid progression of cardiovascular disease seen in diabetic patients with
      nephropathy.

PMID- 16809270
TI  - Spontaneous thrombosis of the pampiniform plexus.
AB  - Spontaneous thrombosis of the pampiniform plexus is a very uncommon clinical
      entity. We present a case of thrombosis of the pampiniform plexus that was
      preoperatively diagnosed as an incarcerated inguinal hernia.

PMID- 16809271
TI  - Assessment of the relational factor in male patients consulting for sexual
      dysfunction: the concept of couple sexual dysfunction.
AB  - In a consecutive series of 1140 male subjects reporting a stable couple
      relationship and different degrees of sexual dysfunction, we evaluated the impact
      of relational factors, as assessed by the Structured Interview on Erectile
      Dysfunction (SIEDY) Scale 2 (exploring, as reported by the patient, menopausal
      symptoms, partner's medical illness interfering with sexual activity, and reduced
      partner desire and climax). We found that the SIEDY Scale 2 is significantly and
      independently associated with erectile dysfunction (ED), delayed ejaculation,
      hypoactive sexual desire, and decreased frequency of intercourse. SIEDY Scale 2
      scores are associated with an advanced age of the partner and a long couple
      relationship, independently from patient's age. In addition, an increased
      relational factor correlates with increased extramarital affairs, conflicts in
      the couple, alcohol abuse, and presence of depressive symptoms, as assessed by
      the Middlesex Hospital Questionnaire. Our results should encourage the
      andrologist to consider the context in which sexual symptoms develop, analyzing
      the relationship and partner's behaviors and diseases. Resolving, or at least
      ameliorating, the relational background and the sexual framework might help in
      treating male sexual dysfunction.

PMID- 16809272
TI  - The Sertoli-spermatid junctional complex adhesion strength is affected in vitro
      by adjudin.
AB  - The actin-based cell-cell adherens junction (AJ) between the Sertoli cell and the
      germ cell in the mammalian testis is important not only in mechanical adhesion of
      the cells, but in the morphogenesis and differentiation of the germ cells. The
      Sertoli ectoplasmic specialization (ES), a specialized type of AJ, is associated
      with Sertoli-spermatid binding and is important in cell-cell adhesion in the
      seminiferous epithelium. Abnormal or absent Sertoli ESs have been associated with
      step-8 spermatid sloughing and oligospermia in conditions associated with reduced
      fertility potential. The reproductive hormones, follicle stimulating hormone
      (FSH), and testosterone (T) have also been shown to play a role in the regulation
      of binding of spermatids at the Sertoli-spermatid junctional complex (STJC).
      Adjudin [1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide] is a potential male
      contraceptive and is thought to exhibit its contraceptive effects by interrupting
      the STJC. It has been shown that this compound induces reversible germ cell loss
      from the seminiferous epithelium, particularly elongating/elongate/round
      spermatids and spermatocytes. Using a micropipette pressure transducing system
      (MPTS) to measure the force needed to detach step-8 spermatids from Sertoli
      cells, this study examined the strength of the STJC in Sertoli-spermatid
      cocultures in the presence of Adjudin (1 ng/mL, 50 ng/mL, 125 ng/mL, or 500 ng/mL
      in EtOH) and hormones [FSH (0.1 micro g/mL, NIDDK-oFSH-20, AFP7028D, 175 x NIH
      FSH-S1), T (100 nM)] to optimize in vitro binding. The average forces required to
      detach the spermatids from the underlying Sertoli cells in the presence of 1
      ng/mL, 50 ng/mL, 125 ng/mL, and 500 ng/mL Adjudin were 18.2 x 10(-10) pN, 14.3 x
      10(-10) pN, 7.74 x 10(-10) pN, and 6.51 x 10(-10) pN, respectively. The average
      force required to detach step-8 spermatids in the presence of vehicle only
      (control) was 19.0 x 10(-10) pN. A significant difference for Adjudin
      concentrations at or above 125 ng/mL was determined by one-way ANOVA (P < .05).
      These data confirm that Adjudin is effective in reducing the strength of the
      STJC, identifying Adjudin as a potential contraceptive agent in the male by
      inducing spermatid sloughing and therefore oligospermia.

PMID- 16809273
TI  - No association of androgen receptor GGN repeat length polymorphism with
      infertility in Indian men.
AB  - Androgens, acting through the androgen receptor (AR), play a role in secondary
      sexual differentiation from the prenatal stage to adulthood, including
      spermatogenesis. The AR gene has 2 polymorphic trinucleotide repeats (CAG and
      GGN) in exon 1. The CAG repeat length polymorphism has been well studied in a
      variety of medical conditions, including male infertility. Many of these studies
      have shown an association of the expanded CAG repeats with male infertility,
      although this is not true for all populations. The GGN repeat, in contrast, has
      been less thoroughly studied. Thus far, only 4 reports worldwide have analyzed
      the GGN repeat, alone or in combination with the CAG repeat, in male infertility
      cases. No such study has been undertaken on infertile Indian men. Therefore, we
      have analyzed AR-GGN repeats in a total of 595 Indian males, including 277
      azoospemric, 97 oligozoospermic, and 21 oligoteratozoospermic cases, along with
      200 normozoospermic controls. The analysis revealed no difference in the mean
      number or the range of the repeat between cases (mean = 21.51 repeats, range 15
      26 repeats) and controls (mean 21.58 repeats, range 15-26 repeats). Furthermore,
      no difference was observed when azoospermic (mean = 21.53 repeats, range 15-26
      repeats), oligozoospermic (mean = 21.46 repeats, range 15-26 repeats), and
      oligoteratozoospermic cases (mean = 21.48, range 19-26 repeats) were compared
      individually with the controls.

PMID- 16809274
TI  - Spermicidal activity of bacterial lipopolysaccharide is only partly due to lipid
      A.
AB  - We have previously shown that co-incubation of Chlamydia trachomatis
      lipopolysaccharide (LPS) leads to premature sperm death by an apoptosis-like
      mechanism. It was always assumed that lipid A is the toxic component of LPS. Here
      we investigate the possible involvement of 3-deoxy-D-manno-octulosonic acid
      (Kdo), which is an additional component of the LPS in C. trachomatis. Highly
      motile preparations of sperm from normozoospermic patients were incubated for 6
      hours with commercial sources of lipid A and Kdo. Conventional lipid A
      inhibitors, polymyxin B (PMB) and anti-CD14 monoclonal antibody (mAb) were used
      to test the ability of both lipid A and Kdo to induce an apoptotic-like response
      in mature sperm. Flow cytometry was used to determine apoptosis by the expression
      of annexin V. Caspase activity was also measured by fluorometry and by the use of
      a pan-caspase inhibitor and caspase-3 inhibitor. Both lipid A and Kdo at 50 micro
      g/mL caused significant mortality of sperm. However, although PMB and anti-CD14
      mAb were inhibitory to the activity of lipid A on sperm, no such effect was seen
      against Kdo. In the presence of either lipid A or Kdo, sperm death was caused by
      an apoptotic-like effect that was caspase mediated. We conclude that Kdo shares
      its spermicidal properties with lipid A and seems to kill sperm in a similar
      manner. These results provide an explanation for higher than expected levels of
      spermicidal activity of LPS that are not caused by lipid A.

PMID- 16809275
TI  - Immunolocalization and possible functional role of PSP-I/PSP-II heterodimer in
      highly extended boar spermatozoa.
AB  - PSP-I/PSP-II heterodimer is a major protein of boar seminal plasma which is able
      to preserve, in vitro, the viability, motility, and mitochondrial activity of
      highly extended boar spermatozoa for at least 5 hours. However, little is known
      about the binding pattern of the heterodimer to the sperm plasma membrane and its
      eventual relation with the maintenance of the sperm functionality. The present
      study investigated the effect of exposing highly extended boar spermatozoa (1
      million/mL) to 1.5 mg/mL of PSP-I/PSP-II for 0.5, 5, and 10 hours at 38 degrees C
      on sperm characteristics and the changes in PSP-I/PSP-II localization as a result
      of both the addition of PSP-I/PSP-II to the extender and the incubation time.
      Exposure of the spermatozoa to PSP-I/PSP-II preserved sperm viability, motility,
      and mitochondrial activity when compared to nonexposed spermatozoa. This
      protective effect lasted for 10 hours (P < .05). After immunolabeling of highly
      extended semen with rabbit monospecific polyclonal antibody against PSP-I/PSP-II,
      the percentage of immunopositive spermatozoa declines over time from 71% (0.5
      hours) to 49% (10 hours). However, more than 80% of spermatozoa remained labeled
      during the 10-hour incubation period if PSP-I/PSP-II was added. Scanning electron
      microscopy revealed 4 different binding patterns. The heterodimer was mainly
      localized to the acrosomal area, being redistributed to the postacrosomal area or
      lost during in vitro incubation. In conclusion, the protective effect of the
      heterodimer appears to be related to its adhesion to the acrosomal area, and the
      loss of this protective effect coincides with a stepwise redistribution of PSP
      I/PSP-II during incubation.

PMID- 16809276
TI  - Enhanced binding of sperm with superior volume regulation to oviductal
      epithelium.
AB  - The plasma membrane is a key organelle with respect to sperm fertilizing ability.
      A sensitive way of testing plasma membrane functionality is to examine the sperm
      ability to moderate its swelling in response to hypo-osmotic stress (volume
      regulatory ability) using an electronic cell counter to assess cell volume
      changes. In this study of frozen-thawed bull sperm, we examined the relationship
      among sperm-oviductal epithelium binding capacity, osmotically induced swelling
      response, volume regulatory ability, and standard spermatologic parameters. Sperm
      cell volume distributions were measured under iso-osmotic conditions and after
      hypo-osmotic stress. The relative volume shift was calculated by comparing modal
      values of the cell volume distributions during transition from iso-osmotic to
      hypo-osmotic conditions. Significant correlations were found between volumetric
      parameters and sperm-oviduct binding capacity. Both the relative volume shift and
      regulative volume decrease correlated positively and significantly with the sperm
      oviduct binding capacity. No significant correlations were found between sperm
      volumetric parameters and any of the standard sperm parameters with the exception
      of forward motility of Percoll-washed sperm. However, the use of multiple
      regression models improved the prediction level for binding capacity when
      motility parameters were combined with membrane integrity and volumetric
      parameters (R2 = .84). Spermatozoa of bulls with high nonreturn rates responded
      to hypotonicity as "perfect osmometers." Subfertile bulls had lower binding
      indices and deficiencies in volume recovery after hypotonic challenge, indicating
      that intact volume regulatory ability is a necessary prerequisite for binding to
      oviductal epithelium and is related to fertility. Volumetric parameters therefore
      could be used as tools in semen evaluation programs.

PMID- 16809277
TI  - Comparative study of four different sperm washing methods using apoptotic markers
      in ram spermatozoa.
AB  - The accurate measurement of semen fertilizing potential is of great importance in
      determining the acceptability of processed semen for breeding purposes. A good
      sperm preparation technique results in a sample with high viability and motility
      and also takes into account other parameters such as the capacitation and
      apoptotic state which could compromise the ability to fertilize an oocyte. In
      this study, we investigate the effects of 4 sperm preparation techniques (a
      dextran/swim-up procedure, discontinuous Percoll density gradient centrifugation,
      sucrose washing, and filtration) on ram sperm quality parameters. Besides the
      evaluation of viability and the capacitation state, we also analyzed the
      apoptotic status of the sperm samples by assessing the phosphatidylserine
      translocation and caspase-3 and -7 activities. This is the first report, to our
      knowledge, that evidences the presence of active caspases in ram sperm. The
      results confirm the better ability of the dextran/swim-up procedure to select
      nonapoptotic spermatozoa, in addition to viable and noncapacitated sperm,
      compared with other sperm preparation methods. This should be considered to
      enhance results of artificial insemination techniques in ovine reproduction.

PMID- 16809278
TI  - Characterization of the multiple conformational States of free monomeric and
      trimeric human immunodeficiency virus envelope glycoproteins after fixation by
      cross-linker.
AB  - The human immunodeficiency virus type 1 (HIV-1) gp120 exterior and gp41
      transmembrane envelope glycoproteins assemble into trimers on the virus surface
      that represent potential targets for antibodies. Potent neutralizing antibodies
      bind the monomeric gp120 glycoprotein with small changes in entropy, whereas
      unusually large decreases in entropy accompany gp120 binding by soluble CD4 and
      less potent neutralizing antibodies. The high degree of conformational
      flexibility in the free gp120 molecule implied by these observations has been
      suggested to contribute to masking the trimer from antibodies that recognize the
      gp120 receptor-binding regions. Here we use cross-linking and recognition by
      antibodies to investigate the conformational states of gp120 monomers and soluble
      and cell surface forms of the trimeric HIV-1 envelope glycoproteins. The fraction
      of monomeric and trimeric envelope glycoproteins able to be recognized after
      fixation was inversely related to the entropic changes associated with ligand
      binding. In addition, fixation apparently limited the access of antibodies to the
      V3 loop and gp41-interactive surface of gp120 only in the context of trimeric
      envelope glycoproteins. The results support a model in which the unliganded
      monomeric and trimeric HIV-1 envelope glycoproteins sample several different
      conformations. Depletion of particular fixed conformations by antibodies allowed
      characterization of the relationships among the conformational states. Potent
      neutralizing antibodies recognize the greatest number of conformations and
      therefore can bind the virion envelope glycoproteins more rapidly and completely
      than weakly neutralizing antibodies. Thus, the conformational flexibility of the
      HIV-1 envelope glycoproteins creates thermodynamic and kinetic barriers to
      neutralization by antibodies directed against the receptor-binding regions of
      gp120.

PMID- 16809279
TI  - Removal of arginine 332 allows human TRIM5alpha to bind human immunodeficiency
      virus capsids and to restrict infection.
AB  - Human TRIM5alpha (TRIM5alpha(hu)) only modestly inhibits human immunodeficiency
      virus type 1 (HIV-1) and does not inhibit simian immunodeficiency virus
      (SIV(mac)). Alteration of arginine 332 in the TRIM5alpha(hu) B30.2 domain to
      proline, the residue found in rhesus monkey TRIM5alpha, has been shown to create
      a potent restricting factor for both HIV-1 and SIV(mac.) Here we demonstrate that
      the potentiation of HIV-1 inhibition results from the removal of a positively
      charged residue at position 332 of TRIM5alpha(hu.) The increase in restricting
      activity correlated with an increase in the ability of TRIM5alpha(hu) mutants
      lacking arginine 332 to bind HIV-1 capsid complexes. A change in the cyclophilin
      A-binding loop of the HIV-1 capsid decreased TRIM5alpha(hu) R332P binding and
      allowed escape from restriction. The ability of TRIM5alpha(hu) to restrict
      SIV(mac) could be disrupted by the presence of any charged residue at position
      332. Thus, charged residues in the v1 region of the TRIM5alpha(hu) B30.2 domain
      can modulate capsid binding and restriction potency. Therapeutic strategies
      designed to neutralize arginine 332 of TRIM5alpha(hu) might potentiate the innate
      resistance of human cells to HIV-1 infection.

PMID- 16809280
TI  - Cross-subtype T-cell immune responses induced by a human immunodeficiency virus
      type 1 group m consensus env immunogen.
AB  - The genetic diversity among globally circulating human immunodeficiency virus
      type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have
      generated a synthetic group M consensus env gene (CON6) for induction of cross
      subtype immune responses and report here a comparative study of T-cell responses
      to this and natural strain env immunogens in a murine model. Three different
      strains of mice were immunized with CON6 as well as subtype A, B, or C env
      immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell
      epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using
      five overlapping Env peptide sets from heterologous subtype A, B, and C viruses.
      The CON6-derived vaccine was immunogenic and induced a greater number of T-cell
      epitope responses than any single wild-type subtype A, B, and C env immunogen and
      similar T-cell responses to a polyvalent vaccine. The responses were comparable
      to within-clade responses but significantly more than between-clade responses.
      The magnitude of the T-cell responses induced by CON6 (measured by individual
      epitope peptides) was also greater than the magnitude of responses induced by
      individual wild-type env immunogens. Though the limited major histocompatibility
      complex repertoire in inbred mice does not necessarily predict responses in
      nonhuman primates and humans, these results suggest that synthetic centralized
      env immunogens represent a promising approach for HIV-1 vaccine design that
      merits further characterization.

PMID- 16809281
TI  - Consistent effects of TSG101 genetic variability on multiple outcomes of exposure
      to human immunodeficiency virus type 1.
AB  - Tumor susceptibility gene 101 (TSG101) encodes a host cellular protein that is
      appropriated by human immunodeficiency virus type 1 (HIV-1) in the budding
      process of viral particles from infected cells. Variation in the coding or
      noncoding regions of the gene could potentially affect the degree of TSG101
      mediated release of viral particles. While the coding regions of the gene were
      found to lack nonsynonymous variants, two polymorphic sites in the TSG101 5' area
      were identified that were associated with the rate of AIDS progression among
      Caucasians. These single-nucleotide polymorphisms (SNPs), located at positions 
      183 and +181 relative to the translation start, specify three haplotypes termed
      A, B, and C, which occur at frequencies of 67%, 21%, and 12%, respectively.
      Haplotype C is associated with relatively rapid AIDS progression, while haplotype
      B is associated with slower disease progression. Both effects were dominant over
      the intermediate haplotype A. The haplotypes also demonstrated parallel effects
      on the rate of CD4 T-cell depletion and viral load increase over time, as well as
      a possible influence on HIV-1 infection. The data raise the hypothesis that
      noncoding variation in TSG101 affects the efficiency of TSG101-mediated release
      of viral particles from infected cells, thereby altering levels of plasma viral
      load and subsequent disease progression.

PMID- 16809282
TI  - Epstein-Barr virus LMP2A enhances B-cell responses in vivo and in vitro.
AB  - Epstein-Barr virus (EBV) establishes latent infections in a significant
      percentage of the population. Latent membrane protein 2A (LMP2A) is an EBV
      protein expressed during latency that inhibits B-cell receptor signaling in
      lymphoblastoid cell lines. In the present study, we have utilized a transgenic
      mouse system in which LMP2A is expressed in B cells that are specific for hen egg
      lysozyme (E/HEL-Tg). To determine if LMP2A allows B cells to respond to antigen,
      E/HEL-Tg mice were immunized with hen egg lysozyme. E/HEL-Tg mice produced
      antibody in response to antigen, indicating that LMP2A allows B cells to respond
      to antigen. In addition, E/HEL-Tg mice produced more antibody and an increased
      percentage of plasma cells after immunization compared to HEL-Tg littermates,
      suggesting that LMP2A increased the antibody response in vivo. Finally, in vitro
      studies determined that LMP2A acts directly on the B cell to increase antibody
      production by augmenting the expansion and survival of the activated B cells, as
      well as increasing the percentage of plasma cells generated. Taken together,
      these data suggest that LMP2A enhances, not diminishes, B-cell-specific antibody
      responses in vivo and in vitro in the E/HEL-Tg system.

PMID- 16809283
TI  - Processing of human cytomegalovirus UL37 mutant glycoproteins in the endoplasmic
      reticulum lumen prior to mitochondrial importation.
AB  - The human cytomegalovirus (HCMV) UL37 glycoprotein (gpUL37) is internally cleaved
      and its products divergently traffic to mitochondria or are retained in the
      secretory pathway. To define the requirements for gpUL37 cleavage, residues -1
      and -3 of the consensus endoplasmic reticulum (ER) signal peptidase I site within
      exon 3 (UL37x3) were replaced by bulky tyrosines (gpUL37 cleavage site mutant I).
      Internal cleavage of this UL37x3 mutant was inhibited, verifying usage of the
      consensus site at amino acids (aa) 193/194. The full-length mitochondrial species
      of gpUL37 cleavage site mutant I was N glycosylated and endoglycosidase H
      sensitive, indicating that ER translocation and processing took place prior to
      its mitochondrial importation. Moreover, these results suggest that internal
      cleavage of gpUL37 is not necessary for its N glycosylation. Partial deletion or
      disruption of the UL37 hydrophobic core immediately upstream of the cleavage site
      resulted in decreased protein abundance, suggesting that the UL37x3 hydrophobic
      alpha-helix contributes to either correct folding or stability of gpUL37.
      Insertion of the UL37x3 hydrophobic core and cleavage site into pUL37(M), a
      splice variant of gpUL37 which lacks these sequences and is neither
      proteolytically cleaved nor N glycosylated, resulted in its internal cleavage and
      N glycosylation. Its NH(2)-terminal fragment, pUL37(M-NH2), was detected more
      abundantly in mitochondria, while its N-glycosylated C-terminal fragment,
      gpUL37(M-COOH), was detected predominantly in the ER in a manner analogous to
      that of gpUL37 cleavage products. These results indicate that UL37x3 aa 178 to
      205 are prerequisite for gpUL37 internal cleavage and alter UL37 protein topology
      allowing N glycosylation of its C-terminal sequences. In contrast, the NH(2)
      terminal UL37x1 hydrophobic leader, present in pUL37x1, pUL37(M), and gpUL37, is
      not cleaved from mature UL37 protein, retaining a membrane anchor for UL37
      isoforms during trafficking. Taken together, these results suggest that HCMV
      gpUL37 undergoes sequential trafficking, during which it is ER translocated,
      processed, and then mitochondrially imported.

PMID- 16809284
TI  - Vaccinia virus intermediate and late promoter elements are targeted by the TATA
      binding protein.
AB  - Vaccinia virus replicates in the cytoplasm of the host cell and encodes its own
      RNA polymerase and transcription factors. The proteins that target the poxvirus
      RNA polymerase to intermediate- and late-class promoters have not been
      identified. In this study, representatives of the intermediate and late promoters
      were characterized at the nucleotide level to identify essential motifs. Both
      intermediate and late viral promoters are shown to have an essential element
      suggestive of TATA boxes, which are potential targets for the TATA-binding
      protein (TBP). Several approaches were used to test for TBP requirement in
      vaccinia virus transcription, including overexpression of TBP, expression of a
      dominant negative mutant of TBP, RNA interference, and expression of adenovirus
      E1A protein, which inactivates TBP. In each case, the results support an
      essential role for TBP in vaccinia virus intermediate- and late-gene
      transcription. These findings indicate that poxviruses have integrated TBP as a
      central feature into an otherwise heterologous transcription system. A model for
      transcriptional switching, in which both intermediate and late promoter elements
      are targeted by TBP that recruits viral transcription factors to assemble a
      functional complex on their cognate promoters and a dysfunctional, repressed
      complex on the other class, is proposed.

PMID- 16809285
TI  - Conformational states of the severe acute respiratory syndrome coronavirus spike
      protein ectodomain.
AB  - The severe acute respiratory syndrome coronavirus enters cells through the
      activities of a spike protein (S) which has receptor-binding (S1) and membrane
      fusion (S2) regions. We have characterized four sequential states of a purified
      recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S
      e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1
      monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition
      from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage
      of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a
      major rearrangement of the trimeric S2 and to formation of rosettes likely to
      represent clusters of elongated, postfusion trimers of S2 associated through
      their fusion peptides. The states and transitions of S suggest conformational
      changes that mediate viral entry into cells.

PMID- 16809286
TI  - Preferential infection shortens the life span of human immunodeficiency virus
      specific CD4+ T cells in vivo.
AB  - CD4(+) T-cell help is essential for effective immune responses to viruses. In
      human immunodeficiency virus (HIV) infection, CD4(+) T cells specific for HIV are
      infected by the virus at higher frequencies than other memory CD4(+) T cells.
      Here, we demonstrate that HIV-specific CD4(+) T cells are barely detectable in
      most infected individuals and that the corresponding CD4(+) T cells exhibit an
      immature phenotype compared to both cytomegalovirus (CMV)-specific CD4(+) T cells
      and other memory CD4(+) T cells. However, in two individuals, we observed a rare
      and diametrically opposed pattern in which HIV-specific CD4(+) T-cell populations
      of large magnitude exhibited a terminally differentiated immunophenotype; these
      cells were not preferentially infected in vivo. Clonotypic analysis revealed that
      the HIV-specific CD4(+) T cells from these individuals were cross-reactive with
      CMV. Thus, preferential infection can be circumvented in the presence of cross
      reactive CD4(+) T cells driven to maturity by coinfecting viral antigens, and
      this physical proximity rather than activation status per se is an important
      determinant of preferential infection based on antigen specificity. These data
      demonstrate that preferential infection reduces the life span of HIV-specific
      CD4(+) T cells in vivo and thereby compromises the generation of effective immune
      responses to the virus itself; further, this central feature in the
      pathophysiology of HIV infection can be influenced by the cross-reactivity of
      responding CD4(+) T cells.

PMID- 16809287
TI  - ICP0 gene expression is a herpes simplex virus type 1 apoptotic trigger.
AB  - Apoptosis is a highly regulated programmed cell death process which is activated
      during normal development and by various stimuli, such as viral infection, which
      disturb cellular metabolism and physiology. That herpes simplex virus type 1 (HSV
      1) induces apoptosis but then prevents its killing of infected cells is well
      established. However, little is known about the viral factor/event which triggers
      the apoptotic process. We previously reported that infections with either (i) a
      temperature-sensitive virus at its nonpermissive temperature which does not
      inject viral DNA into nuclei or (ii) various UV-inactivated wild-type viruses do
      not result in the induction of apoptosis (C. M. Sanfilippo, F. N. W. Chirimuuta,
      and J. A. Blaho, J. Virol. 78:224-239, 2004). This indicates that virus receptor
      binding/attachment to cells, membrane fusion, virion disassembly/tegument
      dispersal, virion RNAs, and capsid translocation to nuclei are not responsible
      for induction and implicates viral immediate-early (IE) gene expression in the
      process. Here, we systematically evaluated the contribution of each IE gene to
      the stimulation of apoptosis. Using a series of viruses individually deleted for
      alpha27, alpha4, and alpha22, we determined that these genes are not required for
      apoptosis induction but rather that their products play roles in its prevention,
      likely through regulatory effects. Sole expression of alpha0 acted as an
      "apoptoxin" that was necessary and sufficient to trigger the cell death cascade.
      Importantly, results using a recombinant virus which contains a stop codon in
      alpha0 showed that it was not the ICP0 protein which acted as the apoptotic
      inducer. Based on these findings, we propose that alpha0 gene expression acts as
      an initial inducer of apoptosis during HSV-1 infection. This represents the first
      description of apoptosis induction in infected cells triggered as a result of
      expression of a single viral gene. Expression of apoptotic viral genes is a
      unique mechanism through which human pathogens may modulate interactions with
      their host cells.

PMID- 16809288
TI  - Sequestration and protection of double-stranded RNA by the betanodavirus b2
      protein.
AB  - Betanodavirus B2 belongs to a group of functionally related proteins from the
      sense-strand RNA virus family Nodaviridae that suppress cellular RNA
      interference. The B2 proteins of insect alphanodaviruses block RNA interference
      by binding to double-stranded RNA (dsRNA), thus preventing Dicer-mediated
      cleavage and the subsequent generation of short interfering RNAs. We show here
      that the fish betanodavirus B2 protein also binds dsRNA. Binding is sequence
      independent, and maximal binding occurs with dsRNA substrates greater than 20 bp
      in length. The binding of B2 to long dsRNA is sufficient to completely block
      Dicer cleavage of dsRNA in vitro. Protein-protein interaction studies indicated
      that B2 interacts with itself and with other dsRNA binding proteins, the
      interaction occurring through binding to shared dsRNA substrates. Induction of
      the dsRNA-dependent interferon response was not antagonized by B2, as the
      interferon-responsive Mx gene of permissive fish cells was induced by wild-type
      viral RNA1 but not by a B2 mutant. The induction of Mx instead relied solely on
      viral RNA1 accumulation, which is impaired in the B2 mutant. Hyperediting of
      virus dsRNA and site-specific editing of 5-HT2C mRNA were both antagonized by B2.
      RNA editing was not, however, observed in transfected wild-type or B2 mutant
      RNA1, suggesting that this pathway does not contribute to the RNA1 accumulation
      defect of the B2 mutant. We thus conclude that betanodavirus B2 is a dsRNA
      binding protein that sequesters and protects both long and short dsRNAs to
      protect betanodavirus from cellular RNA interference.

PMID- 16809289
TI  - Both spike and background genes contribute to murine coronavirus neurovirulence.
AB  - Various strains of mouse hepatitis virus (MHV) exhibit different pathogenic
      phenotypes. Infection with the A59 strain of MHV induces both encephalitis and
      hepatitis, while the highly neurovirulent JHM strain induces a fatal encephalitis
      with little, if any, hepatitis. The pathogenic phenotype for each strain is
      determined by the genetic composition of the viral genome, as well as the host
      immune response. Using isogenic recombinant viruses with A59 background genes
      differing only in the spike gene, we have previously shown that high
      neurovirulence is associated with the JHM spike protein, the protein responsible
      for attachment to the host cell receptor (J. J. Phillips, M. M. Chua, G. F. Rall,
      and S. R. Weiss, Virology 301:109-120, 2002). Using another set of isogenic
      recombinant viruses with JHM background genes expressing either the JHM or A59
      spike, we have further investigated the roles of viral genes in pathogenesis.
      Here, we demonstrate that the high neurovirulence of JHM is associated with
      accelerated spread through the brain and a heightened innate immune response that
      is characterized by high numbers of infiltrating neutrophils and macrophages,
      suggesting an immunopathogenic component to neurovirulence. While expression of
      the JHM spike is sufficient to confer a neurovirulent phenotype, as well as
      increased macrophage infiltration, background genes contribute to virulence as
      well, at least in part, by dictating the extent of the T-cell immune response.

PMID- 16809290
TI  - Neuropilin-1 is involved in human T-cell lymphotropic virus type 1 entry.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is transmitted through a viral
      synapse and enters target cells via interaction with the glucose transporter
      GLUT1. Here, we show that Neuropilin-1 (NRP1), the receptor for semaphorin-3A and
      VEGF-A165 and a member of the immune synapse, is also a physical and functional
      partner of HTLV-1 envelope (Env) proteins. HTLV-1 Env and NRP1 complexes are
      formed in cotransfected cells, and endogenous NRP1 contributes to the binding of
      HTLV-1 Env to target cells. NRP1 overexpression increases HTLV-1 Env-dependent
      syncytium formation. Moreover, overexpression of NRP1 increases both HTLV-1 and
      HTLV-2 Env-dependent infection, whereas down-regulation of endogenous NRP1 has
      the opposite effect. Finally, overexpressed GLUT1, NRP1, and Env form ternary
      complexes in transfected cells, and endogenous NRP1 and GLUT1 colocalize in
      membrane junctions formed between uninfected and HTLV-1-infected T cells. These
      data show that NRP1 is involved in HTLV-1 and HTLV-2 entry, suggesting that the
      HTLV receptor has a multicomponent nature.

PMID- 16809291
TI  - Regulation of adeno-associated virus DNA replication by the cellular TAF-I/set
      complex.
AB  - The Rep proteins of the adeno-associated virus (AAV) are required for viral
      replication in the presence of adenovirus helper functions and as yet poorly
      characterized cellular factors. In an attempt to identify such factors, we
      purified Flag-Rep68-interacting proteins from human cell lysates. Several
      polypeptides were identified by mass spectrometry, among which was ANP32B, a
      member of the acidic nuclear protein 32 family which takes part in the formation
      of the template-activating factor I/Set oncoprotein (TAF-I/Set) complex. The N
      terminus of Rep was found to specifically bind the acidic domain of ANP32B;
      through this interaction, Rep was also able to recruit other members of the TAF
      I/Set complex, including the ANP32A protein and the histone chaperone TAF-I/Set.
      Further experiments revealed that silencing of ANP32A and ANP32B inhibited AAV
      replication, while overexpression of all of the components of the TAF-I/Set
      complex increased de novo AAV DNA synthesis in permissive cells. Besides being
      the first indication that the TAF-I/Set complex participates in wild-type AAV
      replication, these findings have important implications for the generation of
      recombinant AAV vectors since overexpression of the TAF-I/Set components was
      found to markedly increase viral vector production.

PMID- 16809292
TI  - Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived
      from the cells of individuals infected with non-B clades of human
      immunodeficiency virus type 1.
AB  - The majority of global human immunodeficiency virus infections are caused by
      viruses characterized by a GPGQ motif at the tip of the V3 loop. Characterization
      of anti-V3 monoclonal antibodies (MAbs) that neutralize isolates with the GPGQ V3
      motif is an important step in designing vaccines that will induce such Abs.
      Consequently, seven human anti-V3 MAbs derived from the cells of individuals
      infected with non-B-subtype viruses (anti-V3(non-B) MAbs) were generated from the
      cells of individuals from Africa infected with circulating recombinant forms
      CRF02_AG, CRF09_cpx, and CRF13_cpx, each of which contains a subtype A env gene.
      Sequence analysis of plasma viruses revealed a GPGQ motif at the apex of the V3
      loop from six of the seven subjects and a GPGR motif from one subject. The MAbs
      were selected with fusion proteins (FP) containing V3(92UG037.8) or V3(JR-CSF)
      from subtype A or B, respectively. In virus binding assays, five of the seven
      (71%) anti-V3(non-B) MAbs bound to V3-FPs from both subtype A and subtype B,
      while only four of the nine (44%) anti-V3(B) MAbs recognized both V3-FPs. Using
      two neutralization assays, both the anti-V3(non-B) and the anti-V3(B) MAbs
      neutralized subtype B viruses with similar activities, while the anti-V3(non-B)
      MAbs exhibited a tendency toward both increased potency and breadth of
      neutralization against non-B viruses compared to anti-V3(B) MAbs. Statistical
      significance was not achieved, due in large measure to the sizes of the MAb
      panels, but the overall pattern of data strongly suggests that viruses with the
      GPGQ motif at the tip of the V3 loop induce anti-V3 Abs with broader cross
      neutralizing activity than do viruses with the GPGR motif.

PMID- 16809293
TI  - Experimental confirmation of global murine cytomegalovirus open reading frames by
      transcriptional detection and partial characterization of newly described gene
      products.
AB  - Murine cytomegalovirus (MCMV) and human CMV (HCMV) share many features making the
      mouse system a potential small-animal model for HCMV. Although the genomic DNA
      sequence and the predicted open reading frames (ORFs) of MCMV have been
      determined, experimental evidence that the ORFs are actually transcribed has been
      lacking. We developed an MCMV global-DNA microarray that includes all previously
      predicted ORFs and 14 potential ones. A total of 172 ORFs were confirmed to be
      transcribed, including 7 newly discovered ORFs not previously predicted. No gene
      products from 10 previously predicted ORFs were detected by either DNA microarray
      analysis or reverse transcriptase PCR in MCMV-infected mouse fibroblasts,
      although 2 of those were expressed in a macrophage cell line, suggesting that
      potential gene products from these open reading frames are silenced in
      fibroblasts and required in macrophages. Immunohistochemical localization of the
      six newly described ORF products and three recently identified ones in cells
      transfected with the respective construct revealed four of the products in the
      nucleus and five in mitochondria. Analysis of two ORFs using site-directed
      mutagenesis showed that deletion of one of the mitochondrion-localized gene
      products led to significantly decreased replication in fibroblasts.

PMID- 16809294
TI  - Dihydroxythiophenes are novel potent inhibitors of human immunodeficiency virus
      integrase with a diketo acid-like pharmacophore.
AB  - We have identified dihydroxythiophenes (DHT) as a novel series of human
      immunodeficiency virus type 1 (HIV-1) integrase inhibitors with broad antiviral
      activities against different HIV isolates in vitro. DHT were discovered in a
      biochemical integrase high-throughput screen searching for inhibitors of the
      strand transfer reaction of HIV-1 integrase. DHT are selective inhibitors of
      integrase that do not interfere with virus entry, as shown by the inhibition of a
      vesicular stomatitis virus G-pseudotyped retroviral system. Moreover, in
      quantitative real-time PCR experiments, no effect on the synthesis of viral cDNA
      could be detected but rather an increase in the accumulation of 2-long-terminal
      repeat cycles was detected. This suggests that the integration of viral cDNA is
      blocked. Molecular modeling and the structure activity relationship of DHT
      demonstrate that our compound fits into a two-metal-binding motif that has been
      suggested as the essential pharmacophore for diketo acid (DKA)-like strand
      transfer inhibitors (Grobler et al., Proc. Natl. Acad. Sci. USA 99:6661-6666,
      2002.). This notion is supported by the profiling of DHT on retroviral vectors
      carrying published resistance mutations for DKA-like inhibitors where DHT showed
      partial cross-resistance. This suggests that DHT bind to a common site in the
      catalytic center of integrase, albeit with an altered binding mode. Taken
      together, our findings indicate that DHT are novel selective strand transfer
      inhibitors of integrase with a pharmacophore homologous to DKA-like inhibitors.

PMID- 16809295
TI  - The 2.6-Angstrom structure of infectious bursal disease virus-derived T=1
      particles reveals new stabilizing elements of the virus capsid.
AB  - Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a
      double-stranded RNA virus that causes a highly contagious disease in young
      chickens leading to significant economic losses in the poultry industry. The VP2
      protein, the only structural component of the IBDV icosahedral capsid,
      spontaneously assembles into T=1 subviral particles (SVP) when individually
      expressed as a chimeric gene. We have determined the crystal structure of the T=1
      SVP to 2.60 A resolution. Our results show that the 20 trimeric VP2 clusters
      forming the T=1 shell are further stabilized by calcium ions located at the
      threefold icosahedral axes. The structure also reveals a new unexpected domain
      swapping that mediates interactions between adjacent trimers: a short helical
      segment located close to the end of the long C-terminal arm of VP2 is projected
      toward the threefold axis of a neighboring VP2 trimer, leading to a complex
      network of interactions that increases the stability of the T=1 particles.
      Analysis of crystal packing shows that the exposed capsid residues, His253 and
      Thr284, determinants of IBDV virulence and the adaptation of the virus to grow in
      cell culture, are involved in particle-particle interactions.

PMID- 16809296
TI  - Role of invariant Thr80 in human immunodeficiency virus type 1 protease
      structure, function, and viral infectivity.
AB  - Sequence variability associated with human immunodeficiency virus type 1 (HIV-1)
      is useful for inferring structural and/or functional constraints at specific
      residues within the viral protease. Positions that are invariant even in the
      presence of drug selection define critically important residues for protease
      function. While the importance of conserved active-site residues is easily
      understood, the role of other invariant residues is not. This work focuses on
      invariant Thr80 at the apex of the P1 loop of HIV-1, HIV-2, and simian
      immunodeficiency virus protease. In a previous study, we postulated, on the basis
      of a molecular dynamics simulation of the unliganded protease, that Thr80 may
      play a role in the mobility of the flaps of protease. In the present study, both
      experimental and computational methods were used to study the role of Thr80 in
      HIV protease. Three protease variants (T80V, T80N, and T80S) were examined for
      changes in structure, dynamics, enzymatic activity, affinity for protease
      inhibitors, and viral infectivity. While all three variants were structurally
      similar to the wild type, only T80S was functionally similar. Both T80V and T80N
      had decreased the affinity for saquinavir. T80V significantly decreased the
      ability of the enzyme to cleave a peptide substrate but maintained infectivity,
      while T80N abolished both activity and viral infectivity. Additionally, T80N
      decreased the conformational flexibility of the flap region, as observed by
      simulations of molecular dynamics. Taken together, these data indicate that HIV-1
      protease functions best when residue 80 is a small polar residue and that
      mutations to other amino acids significantly impair enzyme function, possibly by
      affecting the flexibility of the flap domain.

PMID- 16809297
TI  - Analyses of phosphorylation events in the rubella virus capsid protein: role in
      early replication events.
AB  - The Rubella virus capsid protein is phosphorylated prior to virus assembly. Our
      previous data are consistent with a model in which dynamic phosphorylation of the
      capsid regulates its RNA binding activity and, in turn, nucleocapsid assembly. In
      the present study, the process of capsid phosphorylation was examined in further
      detail. We show that phosphorylation of serine 46 in the RNA binding region of
      the capsid is required to trigger phosphorylation of additional amino acid
      residues that include threonine 47. This residue likely plays a direct role in
      regulating the binding of genomic RNA to the capsid. We also provide evidence
      which suggests that the capsid is dephosphorylated prior to or during virus
      budding. Finally, whereas the phosphorylation state of the capsid does not
      directly influence the rate of synthesis of viral RNA and proteins or the
      assembly and secretion of virions, the presence of phosphate on the capsid is
      critical for early events in virus replication, most likely the uncoating of
      virions and/or disassembly of nucleocapsids.

PMID- 16809298
TI  - "Self" and "nonself" manipulation of interferon defense during persistent
      infection: bovine viral diarrhea virus resists alpha/beta interferon without
      blocking antiviral activity against unrelated viruses replicating in its host
      cells.
AB  - Bovine viral diarrhea virus (BVDV), together with Classical swine fever virus
      (CSFV) and Border disease virus (BDV) of sheep, belongs to the genus Pestivirus
      of the Flaviviridae. BVDV is either cytopathic (cp) or noncytopathic (ncp), as
      defined by its effect on cultured cells. Infection of pregnant animals with the
      ncp biotype may lead to the birth of persistently infected calves that are
      immunotolerant to the infecting viral strain. In addition to evading the adaptive
      immune system, BVDV evades key mechanisms of innate immunity. Previously, we
      showed that ncp BVDV inhibits the induction of apoptosis and alpha/beta
      interferon (IFN-alpha/beta) synthesis by double-stranded RNA (dsRNA). Here, we
      report that (i) both ncp and cp BVDV block the induction by dsRNA of the Mx
      protein (which can also be induced in the absence of IFN signaling); (ii) neither
      biotype blocks the activity of IFN; and (iii) once infection is established, BVDV
      is largely resistant to the activity of IFN-alpha/beta but (iv) does not
      interfere with the establishment of an antiviral state induced by IFN-alpha/beta
      against unrelated viruses. The results of our study suggest that, in persistent
      infection, BVDV is able to evade a central element of innate immunity directed
      against itself without generally compromising its activity against unrelated
      viruses ("nonself") that may replicate in cells infected with ncp BVDV. This
      highly selective "self" and "nonself" model of evasion of the interferon defense
      system may be a key element in the success of persistent infection in addition to
      immunotolerance initiated by the early time point of fetal infection.

PMID- 16809299
TI  - The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation
      initiation at the rhinovirus type 2 internal ribosome entry site.
AB  - Poliovirus (PV) plus-strand RNA genomes initiate translation in a cap-independent
      manner via an internal ribosome entry site (IRES) in their 5' untranslated
      region. Viral translation is codetermined by cellular IRES trans-acting factors,
      which can influence viral propagation in a cell-type-specific manner. Engineering
      of a poliovirus recombinant devoid of neuropathogenic properties but highly lytic
      in malignant glioma cells was accomplished by exchange of the cognate poliovirus
      IRES with its counterpart from human rhinovirus type 2 (HRV2), generating PV
      RIPO. Neuroblast:glioma heterokaryon analyses revealed that loss of
      neurovirulence is due to trans-dominant repression of PV-RIPO propagation in
      neuronal cells. The double-stranded RNA binding protein 76 (DRBP76) was
      previously identified to bind to the HRV2 IRES in neuronal cells and to inhibit
      PV-RIPO translation and propagation (M. Merrill, E. Dobrikova, and M. Gromeier,
      J. Virol. 80:3347-3356, 2006). The results of size exclusion chromatography
      indicate that DRBP76 heterodimerizes with nuclear factor of activated T cells, 45
      kDa (NF45), in neuronal but not in glioma cells. The DRBP76:NF45 heterodimer
      binds to the HRV2 IRES in neuronal but not in glioma cells. Ribosomal profile
      analyses show that the heterodimer preferentially associates with the translation
      apparatus in neuronal cells and arrests translation at the HRV2 IRES, preventing
      PV-RIPO RNA assembly into polysomes. Results of this study suggest that the
      DRBP76:NF45 heterodimer selectively blocks HRV2 IRES-driven translation
      initiation in neuron-derived cells.

PMID- 16809300
TI  - Increased immunogenicity of human immunodeficiency virus gp120 engineered to
      express Galalpha1-3Galbeta1-4GlcNAc-R epitopes.
AB  - The glycan shield comprised of multiple carbohydrate chains on the human
      immunodeficiency virus (HIV) envelope glycoprotein gp120 helps the virus to evade
      neutralizing antibodies. The present study describes a novel method for
      increasing immunogenicity of gp120 vaccine by enzymatic replacement of sialic
      acid on these carbohydrate chains with Galalpha1-3Galbeta1-4GlcNAc-R (alpha-gal)
      epitopes. These epitopes are ligands for the natural anti-Gal antibody
      constituting approximately 1% of immunoglobulin G in humans. We hypothesize that
      vaccination with gp120 expressing alpha-gal epitopes (gp120(alphagal)) results in
      in vivo formation of immune complexes with anti-Gal, which targets vaccines for
      effective uptake by antigen-presenting cells (APC), due to interaction between
      the Fc portion of the antibody and Fcgamma receptors on APC. This in turn results
      in effective transport of the vaccine to lymph nodes and effective processing and
      presentation of gp120 immunogenic peptides by APC for eliciting a strong anti
      gp120 immune response. This hypothesis was tested in alpha-1,3
      galactosyltransferase knockout mice, which produce anti-Gal. Mice immunized with
      gp120(alphagal) produced anti-gp120 antibodies in titers that were >100-fold
      higher than those measured in mice immunized with comparable amounts of gp120 and
      effectively neutralized HIV. T-cell response, measured by ELISPOT, was much
      higher in mice immunized with gp120(alphagal) than in mice immunized with gp120.
      It is suggested that gp120(alphagal) can serve as a platform for anti-Gal
      mediated targeting of additional vaccinating HIV proteins fused to
      gp120(alphagal), thereby creating effective prophylactic vaccines.

PMID- 16809301
TI  - Sequence analysis and organization of the Neodiprion abietis nucleopolyhedrovirus
      genome.
AB  - Of 30 baculovirus genomes that have been sequenced to date, the only
      nonlepidopteran baculoviruses include the dipteran Culex nigripalpus
      nucleopolyhedrovirus and two hymenopteran nucleopolyhedroviruses that infect the
      sawflies Neodiprion lecontei (NeleNPV) and Neodiprion sertifer (NeseNPV). This
      study provides a complete sequence and genome analysis of the
      nucleopolyhedrovirus that infects the balsam fir sawfly Neodiprion abietis
      (Hymenoptera, Symphyta, Diprionidae). The N. abietis nucleopolyhedrovirus
      (NeabNPV) is 84,264 bp in size, with a G+C content of 33.5%, and contains 93
      predicted open reading frames (ORFs). Eleven predicted ORFs are unique to this
      baculovirus, 10 ORFs have a putative sequence homologue in the NeleNPV genome but
      not the NeseNPV genome, and 1 ORF (neab53) has a putative sequence homologue in
      the NeseNPV genome but not the NeleNPV genome. Specific repeat sequences are
      coincident with major genome rearrangements that distinguish NeabNPV and NeleNPV.
      Genes associated with these repeat regions encode a common amino acid motif,
      suggesting that they are a family of repeated contiguous gene clusters.
      Lepidopteran baculoviruses, similarly, have a family of repeated genes called the
      bro gene family. However, there is no significant sequence similarity between the
      NeabNPV and bro genes. Homologues of early-expressed genes such as ie-1 and lef-3
      were absent in NeabNPV, as they are in the previously sequenced hymenopteran
      baculoviruses. Analyses of ORF upstream sequences identified potential temporally
      distinct genes on the basis of putative promoter elements.

PMID- 16809302
TI  - Hepatitis C virus entry depends on clathrin-mediated endocytosis.
AB  - Due to difficulties in cell culture propagation, the mechanisms of hepatitis C
      virus (HCV) entry are poorly understood. Here, postbinding cellular mechanisms of
      HCV entry were studied using both retroviral particles pseudotyped with HCV
      envelope glycoproteins (HCVpp) and the HCV clone JFH-1 propagated in cell culture
      (HCVcc). HCVpp entry was measured by quantitative real-time PCR after 3 h of
      contact with target cells, and HCVcc infection was quantified by immunoblot
      analysis and immunofluorescence detection of HCV proteins expressed in infected
      cells. The functional role of clathrin-mediated endocytosis in HCV entry was
      assessed by small interfering RNA-mediated clathrin heavy chain depletion and
      with chlorpromazine, an inhibitor of clathrin-coated pit formation at the plasma
      membrane. In both conditions, HCVpp entry and HCVcc infection were inhibited.
      HCVcc infection was also inhibited by pretreating target cells with bafilomycin
      A1 or chloroquine, two drugs known to interfere with endosome acidification.
      These data indicate that HCV enters target cells by clathrin-mediated
      endocytosis, followed by a fusion step from within an acidic endosomal
      compartment.

PMID- 16809303
TI  - The L4 22-kilodalton protein plays a role in packaging of the adenovirus genome.
AB  - Packaging of the adenovirus (Ad) genome into a capsid is absolutely dependent
      upon the presence of a cis-acting region located at the left end of the genome
      referred to as the packaging domain. The functionally significant sequences
      within this domain consist of at least seven similar repeats, referred to as the
      A repeats, which have the consensus sequence 5' TTTG-N(8)-CG 3'. In vitro and in
      vivo binding studies have demonstrated that the adenovirus protein IVa2 binds to
      the CG motif of the packaging sequences. In conjunction with IVa2, another virus
      specific protein binds to the TTTG motifs in vitro. The efficient formation of
      these protein-DNA complexes in vitro was precisely correlated with efficient
      packaging activity in vivo. We demonstrate that the binding activity to the TTTG
      packaging sequence motif is the product of the L4 22-kDa open reading frame.
      Previously, no function had been ascribed to this protein. Truncation of the L4
      22-kDa protein in the context of the viral genome did not reduce viral gene
      expression or viral DNA replication but eliminated the production of infectious
      virus. We suggest that the L4 22-kDa protein, in conjunction with IVa2, plays a
      critical role in the recognition of the packaging domain of the Ad genome that
      leads to viral DNA encapsidation. The L4 22-kDa protein is also involved in
      recognition of transcription elements of the Ad major late promoter.

PMID- 16809304
TI  - Isolation and characterization of human monoclonal antibodies from individuals
      infected with West Nile Virus.
AB  - Monoclonal antibodies (MAbs) neutralizing West Nile Virus (WNV) have been shown
      to protect against infection in animal models and have been identified as a
      correlate of protection in WNV vaccine studies. In the present study, antibody
      repertoires from three convalescent WNV-infected patients were cloned into an
      scFv phage library, and 138 human MAbs binding to WNV were identified. One
      hundred twenty-one MAbs specifically bound to the viral envelope (E) protein and
      four MAbs to the premembrane (prM) protein. Enzyme-linked immunosorbent assay
      based competitive-binding assays with representative E protein-specific MAbs
      demonstrated that 24/51 (47%) bound to domain II while only 4/51 (8%) targeted
      domain III. In vitro neutralizing activity was demonstrated for 12 MAbs, and two
      of these, CR4374 and CR4353, protected mice from lethal WNV challenge at 50%
      protective doses of 12.9 and 357 mug/kg of body weight, respectively. Our data
      analyzing three infected individuals suggest that the human anti-WNV repertoire
      after natural infection is dominated by nonneutralizing or weakly neutralizing
      MAbs binding to domain II of the E protein, while domain III-binding MAbs able to
      potently neutralize WNV in vitro and in vivo are rare.

PMID- 16809305
TI  - Evaluating replication-defective vesicular stomatitis virus as a vaccine vehicle.
AB  - We have generated replication-competent (VSV-C/E1/E2) and nonpropagating
      (VSVDeltaG-C/E1/E2) vesicular stomatitis virus (VSV) contiguously expressing the
      structural proteins of hepatitis C virus (HCV; core [C] and glycoproteins E1 and
      E2) and report on their immunogenicity in murine models. VSV-C/E1/E2 and
      VSVDeltaG-C/E1/E2 expressed high levels of HCV C, E1, and E2, which were
      authentically posttranslationally processed. Both VSV-expressed HCV E1-E2
      glycoproteins were found to form noncovalently linked heterodimers and appeared
      to be correctly folded, as confirmed by coimmunoprecipitation analysis using
      conformationally sensitive anti-HCV-E2 monoclonal antibodies (MAbs). Intravenous
      or intraperitoneal immunization of BALB/c mice with VSV-C/E1/E2 or VSVDeltaG
      C/E1/E2 resulted in significant and surprisingly comparable HCV core or E2
      antibody responses compared to those of control mice. In addition, both virus
      types generated HCV C-, E1-, or E2-specific gamma interferon (IFN-gamma)
      producing CD8(+) T cells, as determined by enzyme-linked immunospot (ELISPOT)
      analysis. Mice immunized with VSVDeltaG-C/E1/E2 were also protected against the
      formation of tumors expressing HCV E2 (CT26-hghE2t) and exhibited CT26-hghE2t
      specific IFN-gamma-producing and E2-specific CD8(+) T-cell activity. Finally,
      recombinant vaccinia virus (vvHCV.S) expressing the HCV structural proteins
      replicated at significantly lower levels when inoculated into mice immunized with
      VSV-C/E1/E2 or VSVDeltaG-C/E1/E2, but not with control viruses. Our data
      therefore illustrate that potentially safer replication-defective VSV can be
      successfully engineered to express high levels of antigenically authentic HCV
      glycoproteins. In addition, this strategy may therefore serve in effective
      vaccine and immunotherapy-based approaches to the treatment of HCV-related
      disease.

PMID- 16809306
TI  - PKR and RNase L contribute to protection against lethal West Nile Virus infection
      by controlling early viral spread in the periphery and replication in neurons.
AB  - West Nile virus (WNV) is a neurotropic, mosquito-borne flavivirus that can cause
      lethal meningoencephalitis. Type I interferon (IFN) plays a critical role in
      controlling WNV replication, spread, and tropism. In this study, we begin to
      examine the effector mechanisms by which type I IFN inhibits WNV infection. Mice
      lacking both the interferon-induced, double-stranded-RNA-activated protein kinase
      (PKR) and the endoribonuclease of the 2',5'-oligoadenylate synthetase-RNase L
      system (PKR(-/-) x RL(-/-)) were highly susceptible to subcutaneous WNV
      infection, with a 90% mortality rate compared to the 30% mortality rate observed
      in congenic wild-type mice. PKR(-/-) x RL(-/-) mice had increased viral loads in
      their draining lymph nodes, sera, and spleens, which led to early viral entry
      into the central nervous system (CNS) and higher viral burden in neuronal
      tissues. Although mice lacking RNase L showed a higher CNS viral burden and an
      increased mortality, they were less susceptible than the PKR(-/-) x RL(-/-) mice;
      thus, we also infer an antiviral role for PKR in the control of WNV infection.
      Notably, a deficiency in both PKR and RNase L resulted in a decreased ability of
      type I IFN to inhibit WNV in primary macrophages and cortical neurons. In
      contrast, the peripheral neurons of the superior cervical ganglia of PKR(-/-) x
      RL(-/-) mice showed no deficiency in the IFN-mediated inhibition of WNV. Our data
      suggest that PKR and RNase L contribute to IFN-mediated protection in a cell
      restricted manner and control WNV infection in peripheral tissues and some
      neuronal subtypes.

PMID- 16809307
TI  - Fitness comparison of thymidine analog resistance pathways in human
      immunodeficiency virus type 1.
AB  - Resistance to zidovudine (ZDV) results from thymidine analog resistance mutations
      (TAMs) at human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT)
      codons 41, 67, 70, 210, 215, and 219. Two mutations are possible at codon 215: Y
      or F. Whereas T215Y occurs alone or with M41L and L210W (TAM-1 pattern), T215F
      rarely occurs with these mutations or by itself; it is found instead with D67N,
      K70R, and K219Q (TAM-2 pattern). The L210W mutation most often occurs with M41L
      and T215Y and rarely occurs with the T215F or TAM-2 mutation. To explain these
      associations, TAMs were introduced into HIV-1(Hxb2) by site-directed mutagenesis
      and expressed in recombinant viruses. Viral replication kinetics, relative
      fitness, and infectivity were tested in the absence or presence of ZDV. Viruses
      carrying the 215Y mutation showed faster replication kinetics and greater
      relative fitness than did T215F mutants in the absence or presence of ZDV. In
      addition, T215Y mutants showed greater infectivity than did wild-type HIV-1 over
      a range of ZDV concentrations, but T215F mutants had only a modest advantage over
      the wild-type virus. Whereas introduction of L210W improved the relative fitness
      of an M41L/T215Y mutant in the presence of ZDV, introduction of this mutation
      into a D67N/K70R/K219Q background resulted in decreased relative fitness in the
      presence or absence of drug. By contrast, introduction of T215F into the
      D67N/K70R/K219Q background increased viral fitness in the presence of ZDV. These
      results help explain why T215Y but not T215F usually emerges as the first major
      TAM, as well as the clustering of L210W with TAM-1 mutations and T215F with TAM-2
      mutations.

PMID- 16809308
TI  - Rapid pathogenesis induced by a vesicular stomatitis virus matrix protein mutant:
      viral pathogenesis is linked to induction of tumor necrosis factor alpha.
AB  - Vesicular stomatitis virus (VSV) matrix (M) protein blocks host mRNA export from
      the nucleus and thereby inhibits interferon induction in infected cells. M
      mutants with mutations of methionine 51 (M51) lack this shutoff function. We
      examined pathogenesis of a VSV M mutant with a deletion of M51 (VSVDeltaM51)
      after intranasal infection of BALB/c mice and found an unexpected phenotype. Mice
      that received VSVDeltaM51 experienced a more rapid but overall less severe weight
      loss than mice that received the recombinant wild-type VSV (rwtVSV). Rapid weight
      loss was not explained by faster initial replication because VSVDeltaM51
      replication was controlled faster than rwtVSV replication in the lungs and did
      not spread systemically like rwtVSV. This faster control of VSVDeltaM51
      correlated with a more rapid induction of interferon in the lung. Because tumor
      necrosis factor alpha (TNF-alpha) is associated with weight loss, we examined TNF
      alpha induction in mice infected with rwtVSV or VSVDeltaM51. We found more-rapid
      induction of TNF-alpha by the mutant at early times after infection, while rwtVSV
      induced more TNF-alpha later in infection. This result suggested that TNF-alpha
      induction might explain both the rapid weight loss caused by the mutant and the
      overall greater weight loss caused by the rwtVSV. Using TNF-alpha knockout mice
      (C57BL/6 background), we showed that weight loss following rwtVSV infection was
      greatly reduced in the absence of TNF-alpha. Although the rapid weight loss
      caused by VSVDeltaM51 was less pronounced in C57BL/6 mice, it was eliminated in
      the absence of TNF-alpha. These results indicate a role for TNF-alpha in the
      pathogenesis of VSV.

PMID- 16809309
TI  - Genetic organization and hypoxic activation of the Kaposi's sarcoma-associated
      herpesvirus ORF34-37 gene cluster.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for
      Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). We previously reported
      that hypoxia activates KSHV lytic replication and that the promoter for open
      reading frame 34 (ORF34) contains a functional hypoxia-responsive element (HRE).
      ORF34 is part of a cluster of lytic genes (ORF34-37) that includes ORF36, a
      phosphotransferase, and ORF37, a shutoff exonuclease. Rapid amplification of cDNA
      ends analysis revealed that they share a common polyadenylation signal but have
      two start sites. Two transcripts were identified, one 3.4 kb encoding ORF35-37,
      and the other 4.2 kb encoding ORF34 and also having coding potential for ORF35
      37. Exposure of PEL cell lines to hypoxia induced messages of lengths consistent
      with those of these transcripts. Reporter assays with Hep3B cells showed
      activation of both transcripts by hypoxia. The ORF34-37 promoter region has six
      consensus HREs. Sequential deletion, site-directed mutagenesis experiments, and
      Northern blot analysis of RNA produced by constructs indicated that the second
      HRE (HRE-2) plays a critical role in the hypoxic activation of both RNA
      transcripts. The ORF35-37 transcript was upregulated by cotransfected hypoxia
      inducible factor (HIF). Electrophoretic mobility shift assays demonstrated that
      HRE-2 and ancillary sequences bind and compete for HIF with hypoxic Hep3B nuclear
      extract. The activation of this gene cluster by hypoxia may have implications for
      the pathogenesis of PEL and KS. Moreover, the activation of ORF36 by hypoxia
      might be exploited to develop targeted therapy for PEL, which arises in a hypoxic
      environment (pleural effusions).

PMID- 16809310
TI  - TORC1 and TORC2 coactivators are required for tax activation of the human T-cell
      leukemia virus type 1 long terminal repeats.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral
      transcription from the long terminal repeats (LTR). Mechanisms through which Tax
      activates LTR have been established, but coactivators of this process remain to
      be identified and characterized. Here we show that all three members of the TORC
      family of transcriptional regulators are coactivators of Tax for LTR-driven
      expression. TORC coactivation requires CREB, but not ATF4 or other bZIP factors.
      Tax physically interacts with TORC1, TORC2, and TORC3 (TORC1/2/3), and the
      depletion of TORC1/2/3 inhibited Tax activity. TORC coactivation can be further
      enhanced by transcriptional coactivator p300. In addition, coactivators in the
      p300 family are required for full activity of Tax independently of TORC1/2/3.
      Thus, both TORC and p300 families of coactivators are essential for optimal
      activation of HTLV-1 transcription by Tax.

PMID- 16809311
TI  - Protein-primed and de novo initiation of RNA synthesis by norovirus 3Dpol.
AB  - Noroviruses (Caliciviridae) are RNA viruses with a single-stranded, positive
      oriented polyadenylated genome. To date, little is known about the replication
      strategy of norovirus, a so-far noncultivable virus. We have examined the
      initiation of replication of the norovirus genome in vitro, using the active
      norovirus RNA-dependent RNA polymerase (3D(pol)), homopolymeric templates, and
      synthetic subgenomic or antisubgenomic RNA. Initiation of RNA synthesis on
      homopolymeric templates as well as replication of subgenomic polyadenylated RNA
      was strictly primer dependent. In this context and as observed for other enteric
      RNA viruses, i.e., poliovirus, a protein-primed initiation of RNA synthesis after
      elongation of the VPg by norovirus 3D(pol) was postulated. To address this
      question, norovirus VPg was expressed in Escherichia coli and purified.
      Incubation of VPg with norovirus 3D(pol) generated VPg-poly(U), which primed the
      replication of subgenomic polyadenylated RNA. In contrast, replication of
      antisubgenomic RNA was not primer dependent, nor did it depend on a leader
      sequence, as evidenced by deletion analysis of the 3' termini of subgenomic and
      antisubgenomic RNA. On nonpolyadenylated RNA, i.e., antisubgenomic RNA, norovirus
      3D(pol) initiated RNA synthesis de novo and terminated RNA synthesis by a poly(C)
      stretch. Interestingly, on poly(C) RNA templates, norovirus 3D(pol) initiated RNA
      synthesis de novo in the presence of high concentrations of GTP. We propose a
      novel model for initiation of replication of the norovirus genome by 3D(pol),
      with a VPg-protein-primed initiation of replication of polyadenylated genomic RNA
      and a de novo initiation of replication of antigenomic RNA.

PMID- 16809312
TI  - Tissue- and tumor-specific targeting of murine leukemia virus-based replication
      competent retroviral vectors.
AB  - Replication-competent retrovirus vectors based on murine leukemia virus (MLV)
      have been shown to effectively transfer therapeutic genes over multiple serial
      infections in cell culture and through solid tumors in vivo with a high degree of
      genomic stability. While simple retroviruses possess a natural tumor selectivity
      in that they can transduce only actively dividing cells, additional tumor
      targeting strategies would nevertheless be advantageous, since tumor cells are
      not the only actively dividing cells. In this study, we used the promiscuous
      murine cytomegalovirus promoter, a chimeric regulatory sequence consisting of the
      hepatitis B virus enhancer II and the human alpha1-antitrypsin (EII-Pa1AT)
      promoter, and a synthetic regulatory sequence consisting of a series of T-cell
      factor binding sites named the CTP4 promoter to generate replicating MLV vectors,
      whereby the last two are transcriptionally restricted to liver- and beta
      catenin/T-cell factor-deregulated cells, respectively. When the heterologous
      promoters were used to replace almost the entire MLV U3 region, including the MLV
      TATA box, vector replication was inefficient since nascent virus particle
      production from infected cells was greatly decreased. Fusion of the heterologous
      promoters lacking the TATA box to the MLV TATA box, however, generated vectors
      which replicated with almost-wild-type kinetics throughout permissive cells while
      exhibiting low or negligible spread in nonpermissive cells. The genomic stability
      of the vectors was shown to be comparable to that of a similar vector containing
      wild-type MLV long terminal repeats, and tropism analysis over repeated infection
      cycles showed that the targeted vectors retained their original specificity.

PMID- 16809313
TI  - Deregulation of eIF4E: 4E-BP1 in differentiated human papillomavirus-containing
      cells leads to high levels of expression of the E7 oncoprotein.
AB  - Infections with high-risk human papillomaviruses (HPVs) are linked to more than
      95% of cervical cancers. HPVs replicate exclusively in differentiated cells and
      the function of the HPV E7 oncoprotein is essential for viral replication. In
      this study, we investigated the mechanism that regulates E7 expression in
      differentiated cells. The level of E7 protein was strongly induced in HPV
      containing Caski, HOK-16B, and BaP-T cells during growth in methylcellulose
      containing medium, a condition that induces differentiation. Enhanced expression
      of E7 was observed between 4 and 8 h of culturing in methylcellulose and was
      maintained for up to 24 h. The increase was not due to altered stability of the
      E7 protein or an increase in the steady-state level of the E7 mRNA. Instead, the
      translation of the E7 mRNA was enhanced during differentiation. More than 70 to
      80% of the E7 mRNA was found in the polysome fractions in the differentiated
      cells. Consistent with this observation, higher levels of the phosphorylated
      translator inhibitor 4E-BP1 were observed in differentiated HPV-containing cells
      but not in differentiated non-HPV tumor cells or primary keratinocytes. The mTOR
      kinase inhibitor rapamycin blocked phosphorylation of 4E-BP1 and significantly
      decreased the level of E7 protein in Caski cells, suggesting that phosphorylation
      of 4E-BP1 is linked to E7 expression. Prevailing models for the molecular
      mechanisms underlying E7 expression have focused largely on transcriptional
      regulation. The results presented in this study demonstrate a significant role of
      the cellular translation machinery to maintain a high level of E7 protein in
      differentiated cells.

PMID- 16809314
TI  - Distinct roles for nucleic acid in in vitro assembly of purified Mason-Pfizer
      monkey virus CANC proteins.
AB  - In contrast to other retroviruses, Mason-Pfizer monkey virus (M-PMV) assembles
      immature capsids in the cytoplasm. We have compared the ability of minimal
      assembly-competent domains from M-PMV and human immunodeficiency virus type 1
      (HIV-1) to assemble in vitro into virus-like particles in the presence and
      absence of nucleic acids. A fusion protein comprised of the capsid and
      nucleocapsid domains of Gag (CANC) and its N-terminally modified mutant
      (DeltaProCANC) were used to mimic the assembly of the viral core and immature
      particles, respectively. In contrast to HIV-1, where CANC assembled efficiently
      into cylindrical structures, the same domains of M-PMV were assembly incompetent.
      The addition of RNA or oligonucleotides did not complement this defect. In
      contrast, the M-PMV DeltaProCANC molecule was able to assemble into spherical
      particles, while that of HIV-1 formed both spheres and cylinders. For M-PMV, the
      addition of purified RNA increased the efficiency with which DeltaProCANC formed
      spherical particles both in terms of the overall amount and the numbers of
      completed spheres. The amount of RNA incorporated was determined, and for both
      rRNA and MS2-RNA, quantities similar to that of genomic RNA were encapsidated.
      Oligonucleotides also stimulated assembly; however, they were incorporated into
      DeltaProCANC spherical particles in trace amounts that could not serve as a
      stoichiometric structural component for assembly. Thus, oligonucleotides may,
      through a transient interaction, induce conformational changes that facilitate
      assembly, while longer RNAs appear to facilitate the complete assembly of
      spherical particles.

PMID- 16809315
TI  - Humoral responses against coimmunized protein antigen but not against alphavirus
      encoded antigens require alpha/beta interferon signaling.
AB  - Viruses typically elicit potent adaptive immune responses, and live-virus-based
      vaccines are among the most efficient human vaccines known. The mechanisms by
      which viruses stimulate adaptive immune responses are not fully understood, but
      activation of innate immune signaling pathways in the early phase of the
      infection may be of importance. In addition to stimulating immune responses to
      viral antigens expressed in infected cells, viruses can also provide adjuvant
      signals to coimmunized protein antigens. Using recombinant Semliki Forest virus
      (rSFV)-based vaccines, we show that rSFV potently enhanced antibody responses
      against coimmunized protein antigens in the absence of other exogenously added
      adjuvants. Elicitation of antibody responses against both virus-encoded antigens
      and coimmunized protein antigens was independent of the signaling via Toll-like
      receptors (TLRs) previously implicated in antiviral responses. In contrast, the
      adjuvant effect of rSFV on coimmunized protein was completely abolished in mice
      lacking the alpha/beta interferon (IFN-alpha/beta) receptor (IFN-AR1),
      demonstrating that IFN-alpha/beta signaling was critical for mediating this
      effect. Antibody responses directed against virus-encoded antigens were intact in
      IFN-AR1(-/-) mice, suggesting that other signals are sufficient to drive immune
      responses against virally encoded antigens. These data provide a basis for the
      adjuvant effect of rSFV and show that different signals are required to stimulate
      antibody responses to virally encoded antigens and to antigens administered as
      purified protein vaccines, together with viral particles.

PMID- 16809316
TI  - Optimal long-term humoral responses to replication-defective herpes simplex virus
      require CD21/CD35 complement receptor expression on stromal cells.
AB  - Replication-defective herpes simplex virus (HSV) strains elicit durable immune
      responses and protect against virulent HSV challenge in mice, despite being
      unable to establish latent infection in neuronal cells. Mechanisms for generating
      long-lived immunity in the absence of viral persistence remain uncertain. In
      animals immunized with replication-defective HSV, durable serum immunoglobulin G
      (IgG) responses were elicited. Surprisingly, Western blot analyses revealed that
      the specificities of antiviral IgG changed over time, and antibody reactivity to
      some viral proteins was detected only very late. Thus, some of the durable IgG
      activity appeared to be contributed by either new or significantly enhanced
      antibody responses at late times. Following immunization, radiation bone marrow
      chimeric mice lacking complement receptors CD21 and CD35 on stromal cells
      elicited only short-lived serum IgG and failed to mount recall responses to
      subsequent HSV exposure. Our results suggest that complement-mediated retention
      of viral antigens by stromal cells, such as follicular dendritic cells, is
      critical for optimal maintenance of antibody responses and B-cell memory
      following vaccination with replication-defective HSV.

PMID- 16809317
TI  - Induction of lactoferrin gene expression in myeloid or mammary gland cells by
      human T-cell leukemia virus type 1 (HTLV-1) tax: implications for milk-borne
      transmission of HTLV-1.
AB  - Human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell
      leukemia, is transmitted vertically via breastfeeding. We have previously
      demonstrated that lactoferrin, a major milk protein, enhances HTLV-1 replication,
      at least in part by upregulating the HTLV-1 long terminal repeat promoter. We now
      report that HTLV-1 infection can induce lactoferrin gene expression. Coculture
      with HTLV-1-infected MT-2 cells increased the levels of lactoferrin mRNA in
      myeloid-differentiated HL-60 cells, as well as MCF-7 cells, models of two
      probable sources (neutrophils and mammary epithelium) of lactoferrin in breast
      milk. MT-2 cell coculture could be replaced with cell-free culture supernatants
      of MT-2 cells to exert the same effect. Furthermore, extracellularly administered
      Tax protein also induced lactoferrin gene expression at physiologically relevant
      concentrations. In transient-expression assays, Tax transactivated the
      lactoferrin gene promoter in HL-60 or MCF-7 cells. Experiments with Tax mutants,
      as well as site-directed mutants of the lactoferrin promoter reporters, indicated
      that the NF-kappaB transactivation pathway is critical for Tax induction of the
      lactoferrin gene promoter activity in myeloid-differentiated HL-60 cells, but not
      in MCF-7 cells. These results suggest that HTLV-1 infection may be able to induce
      expression of lactoferrin in a paracrine manner in the lactic compartment. Our
      findings, in conjunction with our previous study, implicate that mutual
      interaction between HTLV-1 and lactoferrin would benefit milk-borne transmission
      of this virus.

PMID- 16809318
TI  - Factors determining the breadth and potency of neutralization by V3-specific
      human monoclonal antibodies derived from subjects infected with clade A or clade
      B strains of human immunodeficiency virus type 1.
AB  - The neutralizing activities of anti-V3 antibodies for HIV-1 isolates is affected
      both by sequence variation within V3 and by epitope masking by the V1/V2 domain.
      To analyze the relative contribution of V3 sequence variation, chimeric Env genes
      that contained consensus V3 sequences from seven HIV-1 subtypes in the
      neutralization-sensitive SF162 Env backbone were constructed. Resulting viral
      pseudotypes were tested for neutralization by 15 anti-V3 MAbs isolated from
      humans infected with viruses of either subtype B (anti-V3(B) MAbs) or subtype A
      (anti-V3(A) MAbs). Pseudovirions with the subtype B consensus V3 sequence were
      potently neutralized (IC(50) < 0.006 microg/ml) by all but one of these MAbs,
      while pseudovirions with V3 subtypes A, C, F, H, AG, and AE were generally
      neutralized more effectively by anti-V3(A) MAbs than by anti-V3(B) MAbs. A V1/V2
      masked Env version of SF162 Env with the consensus B V3 sequence was also
      neutralized by these MAbs, although with considerably lower potency, while
      similarly masked chimeras with V3 sequences of subtype A, C, or AG were weakly
      neutralized by anti-V3(A) MAbs but not by anti-V3(B) MAbs. Mutations in the V1/V2
      domain of YU-2 Env increased the sensitivity of this highly resistant Env to a
      pool of anti-V3(B) MAbs several thousand-fold. These results demonstrated (i) the
      exceptional sensitivity of representative V3 domains of multiple subtypes to
      neutralization in the absence of epitope masking, (ii) the broader neutralizing
      activity of anti-V3(A) MAbs for viruses containing diverse V3 sequences, and
      (iii) the generality and dominant effect of V1/V2 masking on restriction of V3
      mediated neutralization.

PMID- 16809319
TI  - Comparative analysis of 22 coronavirus HKU1 genomes reveals a novel genotype and
      evidence of natural recombination in coronavirus HKU1.
AB  - We sequenced and compared the complete genomes of 22 strains of coronavirus HKU1
      (CoV HKU1) obtained from nasopharyngeal aspirates of patients with respiratory
      tract infections over a 2-year period. Phylogenetic analysis of 24 putative
      proteins and polypeptides showed that the 22 CoV HKU1 strains fell into three
      clusters (genotype A, 13 strains; genotype B, 3 strains and genotype C, 6
      strains). However, different phylogenetic relationships among the three clusters
      were observed in different regions of their genomes. From nsp4 to nsp6, the
      genotype A strains were clustered with the genotype B strains. For nsp7 and nsp8
      and from nsp10 to nsp16, the genotype A strains were clustered with the genotype
      C strains. From hemagglutinin esterase (HE) to nucleocapsid (N), the genotype B
      strains were clustered closely with the genotype C strains. Bootscan analysis
      showed possible recombination between genotypes B and C from nucleotide positions
      11,500 to 13,000, corresponding to the nsp6-nsp7 junction, giving rise to
      genotype A, and between genotypes A and B from nucleotide positions 21,500 to
      22,500, corresponding to the nsp16-HE junction, giving rise to genotype C.
      Multiple alignments further narrowed the sites of crossover to a 143-bp region
      between nucleotide positions 11,750 and 11,892 and a 29-bp region between
      nucleotide positions 21,502 and 21,530. Genome analysis also revealed various
      numbers of tandem copies of a perfect 30-base acidic tandem repeat (ATR) which
      encodes NDDEDVVTGD and various numbers and sequences of imperfect repeats in the
      N terminus of nsp3 inside the acidic domain upstream of papain-like protease 1
      among the 22 genomes. All 10 CoV HKU1 strains with incomplete imperfect repeats
      (1.4 and 4.4) belonged to genotype A. The present study represents the first
      evidence for natural recombination in coronavirus associated with human
      infection. Analysis of a single gene is not sufficient for the genotyping of CoV
      HKU1 strains but requires amplification and sequencing of at least two gene loci,
      one from nsp10 to nsp16 (e.g., pol or helicase) and another from HE to N (e.g.,
      spike or N). Further studies will delineate whether the ATR is useful for the
      molecular typing of CoV HKU1.

PMID- 16809320
TI  - CD1d mediates T-cell-dependent resistance to secondary infection with
      encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection
      in vivo.
AB  - The innate and adaptive immune responses have evolved distinct strategies for
      controlling different viral pathogens. Encephalomyocarditis virus (EMCV) is a
      picornavirus that can cause paralysis, diabetes, and myocarditis within days of
      infection. The optimal innate immune response against EMCV in vivo requires CD1d.
      Interaction of antigen-presenting cell CD1d with distinct natural killer T-cell
      ("NKT") populations can induce rapid gamma interferon (IFN-gamma) production and
      NK-cell activation. The T-cell response of CD1d-deficient mice (lacking all NKT
      cells) against acute EMCV infection was further studied in vitro and in vivo.
      EMCV persisted at higher levels in CD1d-knockout (KO) splenocyte cultures
      infected in vitro. Furthermore, optimal resistance to repeat cycles of EMCV
      infection in vitro was also shown to depend on CD1d. However, this was not
      reflected in the relative levels of NK-cell activation but rather by the
      responses of both CD4(+) and CD8(+) T-cell populations. Repeated EMCV infection
      in vitro induced less IFN-gamma and alpha interferon (IFN-alpha) from CD1d
      deficient splenocytes than with the wild type. Furthermore, the level of EMCV
      replication in wild-type splenocytes was markedly and specifically increased by
      addition of blocking anti-CD1d antibody. Depletion experiments demonstrated that
      dendritic cells contributed less than the combination of NK and NKT cells to anti
      EMCV responses and that none of these cell types was the main source of IFN
      alpha. Finally, EMCV infection in vivo produced higher levels of viremia in CD1d
      KO mice than in wild-type animals, coupled with significantly less lymphocyte
      activation and IFN-alpha production. These results point to the existence of a
      previously unrecognized mechanism of rapid CD1d-dependent stimulation of the
      antiviral adaptive cellular immune response.

PMID- 16809321
TI  - Localization of ERK/MAP kinase is regulated by the alphaherpesvirus tegument
      protein Us2.
AB  - Many different viruses activate the extracellular signal-regulated kinase
      (ERK)/mitogen-activated protein (MAP) kinase signaling pathway during infection
      and require ERK activation for the efficient execution of their replication
      programs. Despite these findings, no virus-encoded proteins have been identified
      that directly modulate ERK activities. In an effort to determine the function of
      a conserved alphaherpesvirus structural protein called Us2, we screened a yeast
      two-hybrid library derived from NIH 3T3 cells and identified ERK as a Us2
      interacting protein. Our studies indicate that Us2 binds to ERK in virus-infected
      cells, mediates the incorporation of ERK into the virion, and inhibits the
      activation of ERK nuclear substrates. The association of Us2 with ERK leads to
      the sequestration of ERK at the plasma membrane and to a perinuclear vesicular
      compartment, thereby keeping ERK out of the nucleus. Us2 can bind to activated
      ERK, and the data suggest that Us2 does not inhibit ERK enzymatic activity. The
      treatment of cells with U0126, a specific inhibitor of ERK activation, resulted
      in a substantial delay in the release of virus from infected cells that was more
      pronounced with a virus deleted for Us2 than with parental and repaired strains,
      suggesting that both ERK and Us2 activities are required for efficient virus
      replication. This study highlights an additional complexity to the activation of
      ERK by viruses, namely, that localization of active ERK can be altered by virus
      encoded proteins.

PMID- 16809322
TI  - Hypersusceptibility to substrate analogs conferred by mutations in human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) contains
      four structural motifs (A, B, C, and D) that are conserved in polymerases from
      diverse organisms. Motif B interacts with the incoming nucleotide, the template
      strand, and key active-site residues from other motifs, suggesting that motif B
      is an important determinant of substrate specificity. To examine the functional
      role of this region, we performed "random scanning mutagenesis" of 11 motif B
      residues and screened replication-competent mutants for altered substrate analog
      sensitivity in culture. Single amino acid replacements throughout the targeted
      region conferred resistance to lamivudine and/or hypersusceptibility to
      zidovudine (AZT). Substitutions at residue Q151 increased the sensitivity of HIV
      1 to multiple nucleoside analogs, and a subset of these Q151 variants was also
      hypersusceptible to the pyrophosphate analog phosphonoformic acid (PFA). Other
      AZT-hypersusceptible mutants were resistant to PFA and are therefore
      phenotypically similar to PFA-resistant variants selected in vitro and in
      infected patients. Collectively, these data show that specific amino acid
      replacements in motif B confer broad-spectrum hypersusceptibility to substrate
      analog inhibitors. Our results suggest that motif B influences RT-deoxynucleoside
      triphosphate interactions at multiple steps in the catalytic cycle of
      polymerization.

PMID- 16809323
TI  - Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated
      herpesvirus is required for the spindle shape of virus-infected endothelial cells
      and contributes to their proinflammatory phenotype.
AB  - Kaposi's sarcoma (KS) is an inflammatory angioproliferative lesion induced by the
      infection of endothelial cells with the KS-associated herpesvirus (KSHV).
      Infected endothelial cells assume an elongated (spindle) shape that is one of the
      histologic signatures of KS. In vitro, latent viral infection of primary
      endothelial cells (but no other cell type) strikingly recapitulates these
      morphological findings. Here we report that the spindling phenotype involves
      major rearrangement of the actin cytoskeleton and can be attributed to the
      expression of a single viral protein, vFLIP, a known activator of NF-kappaB.
      Consistent with this, the inhibition of NF-kappaB activation blocks vFLIP-induced
      spindling in cultured endothelial cells. vFLIP expression in spindle cells also
      induces the production of a variety of proinflammatory cytokines and cell surface
      adhesion proteins that likely contribute to the inflammatory component of KS
      lesions.

PMID- 16809324
TI  - Involvement of novel human immunodeficiency virus type 1 reverse transcriptase
      mutations in the regulation of resistance to nucleoside inhibitors.
AB  - We characterized 16 additional mutations in human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT) whose role in drug resistance is still unknown
      by analyzing 1,906 plasma-derived HIV-1 subtype B pol sequences from 551 drug
      naive patients and 1,355 nucleoside RT inhibitor (NRTI)-treated patients. Twelve
      mutations positively associated with NRTI treatment strongly correlated both in
      pairs and in clusters with known NRTI resistance mutations on divergent
      evolutionary pathways. In particular, T39A, K43E/Q, K122E, E203K, and H208Y
      clustered with the nucleoside analogue mutation 1 cluster (NAM1;
      M41L+L210W+T215Y). Their copresence in this cluster was associated with an
      increase in thymidine analogue resistance. Moreover, treatment failure in the
      presence of K43E, K122E, or H208Y was significantly associated with higher
      viremia and lower CD4 cell count. Differently, D218E clustered with the NAM2
      pathway (D67N+K70R+K219Q+T215F), and its presence in this cluster determined an
      increase in zidovudine resistance. In contrast, three mutations (V35I, I50V, and
      R83K) negatively associated with NRTI treatment showed negative correlations with
      NRTI resistance mutations and were associated with increased susceptibility to
      specific NRTIs. In particular, I50V negatively correlated with the lamivudine
      selected mutation M184V and was associated with a decrease in M184V/lamivudine
      resistance, whereas R83K negatively correlated with both NAM1 and NAM2 clusters
      and was associated with a decrease in thymidine analogue resistance. Finally, the
      association pattern of the F214L polymorphism revealed its propensity for the
      NAM2 pathway and its strong negative association with the NAM1 pathway. Our study
      provides evidence of novel RT mutational patterns that regulate positively and/or
      negatively NRTI resistance and strongly suggests that other mutations beyond
      those currently known to confer resistance should be considered for improved
      prediction of clinical response to antiretroviral drugs.

PMID- 16809325
TI  - Hepatitis C virus triggers mitochondrial permeability transition with production
      of reactive oxygen species, leading to DNA damage and STAT3 activation.
AB  - Hepatitis C virus (HCV) infection is frequently associated with the development
      of hepatocellular carcinomas and non-Hodgkin's B-cell lymphomas. Previously, we
      reported that HCV infection causes cellular DNA damage and mutations, which are
      mediated by nitric oxide (NO). NO often damages mitochondria, leading to
      induction of double-stranded DNA breaks (DSBs) and accumulation of oxidative DNA
      damage. Here we report that HCV infection causes production of reactive oxygen
      species (ROS) and lowering of mitochondrial transmembrane potential (DeltaPsi(m))
      in in vitro HCV-infected cell cultures. The changes in membrane potential could
      be inhibited by BCL-2. Furthermore, an inhibitor of ROS production, antioxidant N
      acetyl-L-cysteine (NAC), or an inhibitor of NO, 1,400W, prevented the alterations
      of DeltaPsi(m). The HCV-induced DSB was also abolished by a combination of NO and
      ROS inhibitors. These results indicated that the mitochondrial damage and DSBs in
      HCV-infected cells were mediated by both NO and ROS. Among the HCV proteins,
      core, E1, and NS3 are potent ROS inducers: their expression led to DNA damage and
      activation of STAT3. Correspondingly, core-protein-transgenic mice showed
      elevated levels of lipid peroxidation and oxidatively damaged DNA. These HCV
      studies thus identified ROS, along with the previously identified NO, as the
      primary inducers of DSBs and mitochondrial damage in HCV-infected cells.

PMID- 16809326
TI  - Transmission of simian immunodeficiency virus SIVcpz and the evolution of
      infection in the presence and absence of concurrent human immunodeficiency virus
      type 1 infection in chimpanzees.
AB  - Current data suggest that the human immunodeficiency virus type 1 (HIV-1)
      epidemic arose by transmission of simian immunodeficiency virus (SIV) SIVcpz from
      a subspecies of common chimpanzees (Pan troglodytes troglodytes) to humans.
      SIVcpz of chimpanzees is itself a molecular chimera of SIVs from two or more
      different monkey species, suggesting that recombination was made possible by
      coinfection of one individual animal with different lentiviruses. However, very
      little is known about SIVcpz transmission and the susceptibility to lentivirus
      coinfection of its natural host, the chimpanzee. Here, it is revealed that either
      infected plasma or peripheral blood mononuclear cells readily confer infection
      when exposure occurs by the intravenous or mucosal route. Importantly, the
      presence of preexisting HIV-1 infection did not modify the kinetics of SIVcpz
      infection once it was established by different routes. Although humoral responses
      appeared as early as 4 weeks postinfection, neutralization to SIVcpz-ANT varied
      markedly between animals. Analysis of the SIVcpz env sequence over time revealed
      the emergence of genetic viral variants and persistent SIVcpz RNA levels of
      between 10(4) and 10(5) copies/ml plasma regardless of the presence or absence of
      concurrent HIV-1 infection. These unique data provide important insight into
      possible routes of transmission, the kinetics of acute SIVcpz infection, and how
      readily coinfection with SIVcpz and other lentiviruses may be established as
      necessary preconditions for potential recombination.

PMID- 16809327
TI  - The capsid protein of beak and feather disease virus binds to the viral DNA and
      is responsible for transporting the replication-associated protein into the
      nucleus.
AB  - Circoviruses lack an autonomous DNA polymerase and are dependent on the
      replication machinery of the host cell for de novo DNA synthesis. Accordingly,
      the viral DNA needs to cross both the plasma membrane and the nuclear envelope
      before replication can occur. Here we report on the subcellular distribution of
      the beak and feather disease virus (BFDV) capsid protein (CP) and replication
      associated protein (Rep) expressed via recombinant baculoviruses in an insect
      cell system and test the hypothesis that the CP is responsible for transporting
      the viral genome, as well as Rep, across the nuclear envelope. The intracellular
      localization of the BFDV CP was found to be directed by three partially
      overlapping bipartite nuclear localization signals (NLSs) situated between
      residues 16 and 56 at the N terminus of the protein. Moreover, a DNA binding
      region was also mapped to the N terminus of the protein and falls within the
      region containing the three putative NLSs. The ability of CP to bind DNA, coupled
      with the karyophilic nature of this protein, strongly suggests that it may be
      responsible for nuclear targeting of the viral genome. Interestingly, whereas Rep
      expressed on its own in insect cells is restricted to the cytoplasm, coexpression
      with CP alters the subcellular localization of Rep to the nucleus, strongly
      suggesting that an interaction with CP facilitates movement of Rep into the
      nucleus.

PMID- 16809329
TI  - Activation of triggering receptor expressed on myeloid cells-1 on human
      neutrophils by marburg and ebola viruses.
AB  - Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family
      Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High
      viral burden is coincident with inadequate adaptive immune responses and robust
      inflammatory responses, and virus-mediated dysregulation of early host defenses
      has been proposed. Recently, a novel class of innate receptors called the
      triggering receptors expressed in myeloid cells (TREM) has been discovered and
      shown to play an important role in innate inflammatory responses and sepsis.
      Here, we report that MARV and EBOV activate TREM-1 on human neutrophils,
      resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of
      intracellular calcium, secretion of proinflammatory cytokines, and phenotypic
      changes. A peptide specific to TREM-1 diminished the release of tumor necrosis
      factor alpha by filovirus-activated human neutrophils in vitro, and a soluble
      recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that
      otherwise occurred on neutrophils exposed to filoviruses. These data imply direct
      activation of TREM-1 by filoviruses and also indicate that neutrophils may play a
      prominent role in the immune and inflammatory responses to filovirus infections.

PMID- 16809328
TI  - Passive sexual transmission of human immunodeficiency virus type 1 variants and
      adaptation in new hosts.
AB  - Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle
      for the design of a successful vaccine. Certain viral polymorphisms encode human
      leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited
      vaccine protection. Although transmission of immune escape variants has been
      reported, the overall extent to which this phenomenon occurs in populations and
      the degree to which it contributes to HIV-1 viral evolution are unknown.
      Selection on the HIV-1 env gene at transmission favors neutralization-sensitive
      variants, but it is not known to what degree selection acts on the internal HIV-1
      proteins to restrict or enhance the transmission of immune escape variants.
      Studies have suggested that HLA class I may determine susceptibility to HIV-1
      infection, but a definitive role for HLA at transmission remains unproven.
      Comparing populations of acute seroconverters and chronically infected patients,
      we found no evidence of selection acting to restrict transmission of HIV-1
      variants. We found that statistical associations previously reported in chronic
      infection between viral polymorphisms and HLA class I alleles are not present in
      acute infection, suggesting that the majority of viral polymorphisms in these
      patients are the result of transmission rather than de novo adaptation. Using
      four episodes of HIV-1 transmission in which the donors and recipients were both
      sampled very close to the time of infection we found that, despite a transmission
      bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency
      dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral
      variants, each episode is a highly individual antigenic challenge. Host-specific,
      idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of
      immunization based on consensus sequences.

PMID- 16809330
TI  - Vaccinia virus activation of CCR5 invokes tyrosine phosphorylation signaling
      events that support virus replication.
AB  - Vaccinia virus, a poxvirus, produces structurally distinct forms of virions for
      which the immediate events following cell entry are ill-defined. We provide
      evidence that intracellular mature virus (IMV) enters both permissive and
      nonpermissive T-cell lines and that introduction of CCR5 into nonpermissive mouse
      fibroblasts or human primary T cells renders the cells permissive for vaccinia
      replication. Notably, T cells expressing CCR5 in which tyrosine 339 in the
      intracellular region is replaced by phenylalanine no longer support virus
      replication or virus-inducible activation of specific host cell signaling
      effectors IRS-2, Grb2, and Erk1/2. We show that following IMV entry into the
      cell, the intact but not the tyrosine-deficient CCR5 is rapidly internalized and
      colocalizes with virus. This colocalization precedes virus-inducible signaling
      and replication.

PMID- 16809331
TI  - Infection of naive target cells with virus-like particles: implications for the
      function of ebola virus VP24.
AB  - Infectious virus-like particle (iVLP) systems have recently been established for
      several negative-strand RNA viruses, including the highly pathogenic Zaire
      ebolavirus (ZEBOV), and allow study of the viral life cycle under biosafety level
      2 conditions. However, current systems depend on the expression of viral helper
      nucleocapsid proteins in target cells, thus making it impossible to determine
      whether ribonucleoprotein complexes transferred by iVLPs are able to facilitate
      initial transcription, an indispensable step in natural infection. Here we
      describe a ZEBOV iVLP system which overcomes this limitation and show that VP24
      is essential for the formation of a functional ribonucleoprotein complex.

PMID- 16809332
TI  - Heparan sulfate proteoglycan binding properties of adeno-associated virus
      retargeting mutants and consequences for their in vivo tropism.
AB  - Adeno-associated virus type 2 (AAV-2) targeting vectors have been generated by
      insertion of ligand peptides into the viral capsid at amino acid position 587.
      This procedure ablates binding of heparan sulfate proteoglycan (HSPG), AAV-2's
      primary receptor, in some but not all mutants. Using an AAV-2 display library, we
      investigated molecular mechanisms responsible for this phenotype, demonstrating
      that peptides containing a net negative charge are prone to confer an HSPG
      nonbinding phenotype. Interestingly, in vivo studies correlated the inability to
      bind to HSPG with liver and spleen detargeting in mice after systemic
      application, suggesting several strategies to improve efficiency of AAV-2
      retargeting to alternative tissues.

PMID- 16809333
TI  - Evolutionary history of the closely related group 2 coronaviruses: porcine
      hemagglutinating encephalomyelitis virus, bovine coronavirus, and human
      coronavirus OC43.
AB  - The close genetic and antigenic relatedness among the group 2 coronaviruses human
      coronavirus OC43 (HCoV-OC43), bovine coronavirus (BCoV), and porcine
      hemagglutinating encephalomyelitis virus (PHEV) suggests that these three viruses
      with different host specificities diverged fairly recently. In this study, we
      determined the complete genomic sequence of PHEV (strain PHEV-VW572), revealing
      the presence of a truncated group 2-specific ns2 gene in PHEV in comparison to
      other group 2 coronaviruses. Using a relaxed molecular clock approach, we
      reconstructed the evolutionary relationships between PHEV, BCoV, and HCoV-OC43 in
      real-time units, which indicated relatively recent common ancestors for these
      species-specific coronaviruses.

PMID- 16809334
TI  - Modest but reproducible inhibition of human immunodeficiency virus type 1
      infection in macrophages following LEDGFp75 silencing.
AB  - LEDGFp75 is a cellular protein which binds human immunodeficiency virus type 1
      (HIV-1) integrase with high specificity and affinity but whose function in
      infection has not been defined. We infected LEDGFp75-deficient primary
      macrophages with wild-type HIV in order to assess potential infection phenotypes
      which would provide clues to LEDGFp75 function. Silencing of LEDGFp75 by 70 to
      80% resulted in an average of 53% reduced infection of macrophages by HIV.
      Analysis of infection intermediates showed that integration, but not two-long
      terminal-repeat (2LTR) circles or late cDNAs, was reduced up to 74% in LEDGFp75
      deficient macrophages. Therefore, LEDGFp75 has a modest involvement in HIV-1
      integration in macrophages.

PMID- 16809335
TI  - Epstein-Barr virus shed in saliva is high in B-cell-tropic glycoprotein gp42.
AB  - Epstein-Barr virus is an orally transmitted human herpesvirus that infects
      epithelial cells and establishes latency in memory B lymphocytes. Movement of
      virus between the two cell types is facilitated by changes in amounts of an
      envelope glycoprotein, gp42, which are effected by interaction of gp42 with HLA
      class II in a B cell. Here we used the differential ability of virus to bind to
      CD21-positive B cells and CD21-negative epithelial cells, which is also
      influenced by levels of gp42, to determine that the majority of virus shed in
      saliva is derived from an HLA class II-negative cell.

PMID- 16809336
TI  - Cyclooxygenase-2 induction by arsenite is through a nuclear factor of activated T
      cell-dependent pathway and plays an antiapoptotic role in Beas-2B cells.
AB  - Arsenite is a well known metalloid human carcinogen, and epidemiological evidence
      has demonstrated its association with the increased incidence of lung cancer.
      However, the mechanism involved in its lung carcinogenic effect remains obscure.
      The current study demonstrated that exposure of human bronchial epithelial cells
      (Beas-2B) to arsenite resulted in a marked induction of cyclooxygenase (COX)-2,
      an important mediator for inflammation and tumor promotion. Exposure of the Beas
      2B cells to arsenite also led to significant transactivation of nuclear factor of
      activated T-cells (NFAT), but not activator protein-1 (AP-1) and NFkappaB,
      suggesting that NFAT, rather than AP-1 or NFkappaB, is implicated in the
      responses of Beas-2B cells to arsenite exposure. Furthermore, we found that
      inhibition of the NFAT pathway by either chemical inhibitors, dominant negative
      mutants of NFAT, or NFAT3 small interference RNA resulted in the impairment of
      COX-2 induction and caused cell apoptosis in Beas-2B cells exposed to arsenite.
      Site-directed mutation of two putative NFAT binding sites between-111 to +65 in
      the COX-2 promoter region eliminated the COX-2 transcriptional activity induced
      by arsenite, confirming that those two NFAT binding sites in the COX-2 promoter
      region are critical for COX-2 induction by arsenite. Moreover, knockdown of COX-2
      expression by COX-2-specific small interference RNA also led to an increased cell
      apoptosis in Beas-2B cells upon arsenite exposure. Together, our results
      demonstrate that COX-2 induction by arsenite is through NFAT3-dependent and AP-1-
      or NFkappaB-independent pathways and plays a crucial role in antagonizing
      arsenite-induced cell apoptosis in human bronchial epithelial Beas-2B cells.

PMID- 16809337
TI  - Structure of the N-terminal ankyrin repeat domain of the TRPV2 ion channel.
AB  - The TRPV ion channels mediate responses to many sensory stimuli including heat,
      low pH, neuropeptides, and chemical ligands. All TRPV subfamily members contain
      an intracellular N-terminal ankyrin repeat domain (ARD), a prevalent protein
      interaction motif. The 1.6-A crystal structure of the TRPV2-ARD, with six ankyrin
      repeats, reveals several atypical structural features. Repeats one through three
      display unusually long and flexible fingers with a large number of exposed
      aromatic residues, whereas repeats five and six have unusually long outer
      helices. Furthermore, a large counterclockwise twist observed in the stacking of
      repeats four and five breaks the regularity of the domain, altering the shape of
      surfaces available for interactions with proteins or other cellular ligands. Both
      solution studies and crystal packing interactions indicate that the TRPV2-ARD
      does not form homo-oligomers, suggesting that the ARD of TRPV ion channels may be
      used for interactions with regulatory factors rather than in promoting tetrameric
      assembly of the ion channels.

PMID- 16809338
TI  - Arrestin serves as a molecular switch, linking endogenous alpha2-adrenergic
      receptor to SRC-dependent, but not SRC-independent, ERK activation.
AB  - Our previous studies have demonstrated that neither receptor endocytosis nor
      arrestin is required for ERK activation by the alpha2-adrenergic receptor (Wang,
      Q., Zhao, J., Brady, A. E., Feng, J., Allen, P. B., Lefkowitz, R. J., Greengard,
      P., and Limbird, L. E. (2004) Science 304, 1940-1944). The present studies
      address whether arrestin plays a role in determining the route of alpha2AR-evoked
      ERK signaling activation, taking advantage of endogenous expression of the
      alpha(2A)AR subtype in mouse embryonic fibroblasts (MEFs) and the availability of
      MEFs without arrestin expression (derived from Arr2,3-/- mice). Our data
      demonstrate that the endogenous alpha(2A)AR evokes ERK phosphorylation through
      both a Src-dependent and a Src-independent pathway, both of which are G protein
      dependent and converge on the Ras-Raf-MEK pathway. Arrestin is essential to
      recruit Src to this process, as alpha(2A)AR-mediated ERK signaling in Arr2,3-/-
      MEFs does not involve Src. Stimulation of alpha(2A)AR enhances arrestin-Src
      interaction and promotes activation of Src. alpha2 agonists have similar
      potencies in stimulating Src-dependent and Src-independent ERK phosphorylation in
      wild-type and Arr2,3-/- cells, respectively. However, Src-independent alpha(2A)AR
      mediated ERK stimulation has both a longer duration of activation and a more
      rapid translocation of pERK into the nucleus when compared with Src-dependent
      activation. These data not only affirm the role of arrestin as an escort for
      signaling molecules such as Src family kinases but also demonstrate the impact of
      arrestin-dependent modulation on both the temporal and spatial properties of ERK
      activation.

PMID- 16809339
TI  - Topography of the prostaglandin endoperoxide H2 synthase-2 in membranes.
AB  - The topology of association of the monotopic protein cyclooxygenase-2 (COX-2)
      with membranes has been examined using EPR spectroscopy of spin-labeled
      recombinant human COX-2. Twenty-four mutants, each containing a single free
      cysteine substituted for an amino acid in the COX-2 membrane binding domain were
      expressed using the baculovirus system and purified, then conjugated with a
      nitroxide spin label and reconstituted into liposomes. Determining the relative
      accessibility of the nitroxide-tagged amino acid side chains for the solubilized
      COX-2 mutants, or COX-2 reconstituted into liposomes to nonpolar (oxygen) and
      polar (NiEDDA or CrOx) paramagnetic reagents allowed us to map the topology of
      COX-2 interaction with the lipid bilayer. When spin-labeled COX-2 was
      reconstituted into liposomes, EPR power saturation curves showed that side chains
      for all but two of the 24 mutants tested had limited accessibility to both polar
      and nonpolar paramagnetic relaxation agents, indicating that COX-2 associates
      primarily with the interfacial membrane region near the glycerol backbone and
      phospholipid head groups. Two amino acids, Phe(66) and Leu(67), were readily
      accessible to the non-polar relaxation agent oxygen, and thus likely inserted
      into the hydrophobic core of the lipid bilayer. However these residues are co
      linear with amino acids in the interfacial region, so their extension into the
      hydrophobic core must be relatively shallow. EPR and structural data suggest that
      membrane interaction of COX-2 is also aided by partitioning of 4 aromatic amino
      acids, Phe(59), Phe(66), Tyr(76), and Phe(84) to the interfacial region, and by
      the electrostatic interactions of two basic amino acids, Arg(62) and Lys(64),
      with the phospholipid head groups.

PMID- 16809340
TI  - Structural and computational characterization of the SHV-1 beta-lactamase-beta
      lactamase inhibitor protein interface.
AB  - Beta-lactamase inhibitor protein (BLIP) binds a variety of class A beta
      lactamases with affinities ranging from micromolar to picomolar. Whereas the TEM
      1 and SHV-1 beta-lactamases are almost structurally identical, BLIP binds TEM-1
      approximately 1000-fold tighter than SHV-1. Determining the underlying source of
      this affinity difference is important for understanding the molecular basis of
      beta-lactamase inhibition and mechanisms of protein-protein interface specificity
      and affinity. Here we present the 1.6A resolution crystal structure of SHV
      1.BLIP. In addition, a point mutation was identified, SHV D104E, that increases
      SHV.BLIP binding affinity from micromolar to nanomolar. Comparison of the SHV
      1.BLIP structure with the published TEM-1.BLIP structure suggests that the
      increased volume of Glu-104 stabilizes a key binding loop in the interface.
      Solution of the 1.8A SHV D104K.BLIP crystal structure identifies a novel
      conformation in which this binding loop is removed from the interface. Using
      these structural data, we evaluated the ability of EGAD, a program developed for
      computational protein design, to calculate changes in the stability of mutant
      beta-lactamase.BLIP complexes. Changes in binding affinity were calculated within
      an error of 1.6 kcal/mol of the experimental values for 112 mutations at the TEM
      1.BLIP interface and within an error of 2.2 kcal/mol for 24 mutations at the SHV
      1.BLIP interface. The reasonable success of EGAD in predicting changes in
      interface stability is a promising step toward understanding the stability of the
      beta-lactamase.BLIP complexes and computationally assisted design of tight
      binding BLIP variants.

PMID- 16809341
TI  - Cytocidal actions of parasporin-2, an anti-tumor crystal toxin from Bacillus
      thuringiensis.
AB  - Parasporin-2, a new crystal protein derived from noninsecticidal and nonhemolytic
      Bacillus thuringiensis, recognizes and kills human liver and colon cancer cells
      as well as some classes of human cultured cells. Here we report that a potent
      proteinase K-resistant parasporin-2 toxin shows specific binding to and a variety
      of cytocidal effects against human hepatocyte cancer cells. Cleavage of the N
      terminal region of parasporin-2 was essential for the toxin activity, whereas C
      terminal digestion was required for rapid cell injury. Protease-activated
      parasporin-2 induced remarkable morphological alterations, cell blebbing,
      cytoskeletal alterations, and mitochondrial and endoplasmic reticulum
      fragmentation. The plasma membrane permeability was increased immediately after
      the toxin treatment and most of the cytoplasmic proteins leaked from the cells,
      whereas mitochondrial and endoplasmic reticulum proteins remained in the
      intoxicated cells. Parasporin-2 selectively bound to cancer cells in slices of
      liver tumor tissues and susceptible human cultured cells and became localized in
      the plasma membrane until the cells were damaged. Thus, parasporin-2 acts as a
      cytolysin that permeabilizes the plasma membrane with target cell specificity and
      subsequently induces cell decay.

PMID- 16809342
TI  - Distinct early folding and aggregation properties of Alzheimer amyloid-beta
      peptides Abeta40 and Abeta42: stable trimer or tetramer formation by Abeta42.
AB  - The amyloid beta peptide (Abeta), composed of 40 or 42 amino acids, is a critical
      component in the etiology of the neurodegenerative Alzheimer disease. Abeta is
      prone to aggregate and forms amyloid fibrils progressively both in vitro and in
      vivo. To understand the process of amyloidogenesis, it is pivotal to examine the
      initial stages of the folding process. We examined the equilibrium folding
      properties, assembly states, and stabilities of the early folding stages of
      Abeta40 and Abeta42 prior to fibril formation. We found that Abeta40 and Abeta42
      have different conformations and assembly states upon refolding from their
      unfolded ensembles. Abeta40 is predominantly an unstable and collapsed monomeric
      species, whereas Abeta42 populates a stable structured trimeric or tetrameric
      species at concentrations above approximately 12.5 microm. Thermodynamic analysis
      showed that the free energies of Abeta40 monomer and Abeta42 trimer/tetramer are
      approximately 1.1 and approximately 15/ approximately 22 kcal/mol, respectively.
      The early aggregation stages of Abeta40 and Abeta42 contain different solvent
      exposed hydrophobic surfaces that are located at the sequences flanking its
      protease-resistant segment. The amyloidogenic folded structure of Abeta is
      important for the formation of spherical beta oligomeric species. However, beta
      oligomers are not an obligatory intermediate in the process of fibril formation
      because oligomerization is inhibited at concentrations of urea that have no
      effect on fibril formation. The distinct initial folding properties of Abeta40
      and Abeta42 may play an important role in the higher aggregation potential and
      pathological significance of Abeta42.

PMID- 16809343
TI  - PfPKB, a protein kinase B-like enzyme from Plasmodium falciparum: II.
      Identification of calcium/calmodulin as its upstream activator and dissection of
      a novel signaling pathway.
AB  - Intracellular cell signaling cascades of protozoan parasite Plasmodium falciparum
      are not clearly understood. We have reported previously (Kumar, A., Vaid, A.,
      Syin, C., and Sharma, P. (2004) J. Biol. Chem. 279, 24255-24264) the
      identification and characterization of a protein kinase B-like enzyme in P.
      falciparum (PfPKB). PfPKB lacks the phosphoinositide-interacting pleckstrin
      homology domain present in mammalian protein kinase B. Therefore, the mechanism
      of PfPKB regulation was expected to be different from that of the host and had
      remained unknown. We have identified calmodulin (CaM) as the regulator of PfPKB
      activity. A CaM binding domain was mapped in the N-terminal region of PfPKB. CaM,
      in a calcium-dependent manner, interacts with this domain and activates PfPKB.
      CaM associates with PfPKB in the parasite and regulates its activity. Furthermore
      phospholipase C acts as an upstream regulator of this cascade as it facilitates
      the release of calcium from intracellular stores. This is one of the first
      multicomponent signaling pathways to be dissected in the malaria parasite.

PMID- 16809344
TI  - Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes
      macrophage recruitment and insulin resistance.
AB  - Adipose tissue expression and circulating concentrations of monocyte
      chemoattractant protein-1 (MCP-1) correlate positively with adiposity. To
      ascertain the roles of MCP-1 overexpression in adipose, we generated transgenic
      mice by utilizing the adipocyte P2 (aP2) promoter (aP2-MCP-1 mice). These mice
      had higher plasma MCP-1 concentrations and increased macrophage accumulation in
      adipose tissues, as confirmed by immunochemical, flow cytometric, and gene
      expression analyses. Tumor necrosis factor-alpha and interleukin-6 mRNA levels in
      white adipose tissue and plasma non-esterified fatty acid levels were increased
      in transgenic mice. aP2-MCP-1 mice showed insulin resistance, suggesting that
      inflammatory changes in adipose tissues may be involved in the development of
      insulin resistance. Insulin resistance in aP2-MCP-1 mice was confirmed by
      hyperinsulinemic euglycemic clamp studies showing that transgenic mice had lower
      rates of glucose disappearance and higher endogenous glucose production than wild
      type mice. Consistent with this, insulin-induced phosphorylations of Akt were
      significantly decreased in both skeletal muscles and livers of aP2-MCP-1 mice.
      MCP-1 pretreatment of isolated skeletal muscle blunted insulin-stimulated glucose
      uptake, which was partially restored by treatment with the MEK inhibitor U0126,
      suggesting that circulating MCP-1 may contribute to insulin resistance in aP2-MCP
      1 mice. We concluded that both paracrine and endocrine effects of MCP-1 may
      contribute to the development of insulin resistance in aP2-MCP-1 mice.

PMID- 16809345
TI  - Inhibition of platelet-derived growth factor-BB-induced receptor activation and
      fibroblast migration by hyaluronan activation of CD44.
AB  - The extracellular matrix molecule hyaluronan was found to suppress platelet
      derived growth factor (PDGF) beta-receptor activation and PDGF-BB-induced
      migration of primary human dermal fibroblasts. The suppressive effect of
      hyaluronan was neutralized by a monoclonal antibody that specifically inhibits
      hyaluronan binding to its receptor CD44. Moreover, co-immunoprecipitation
      experiments showed that the PDGF beta-receptor and CD44 can form a complex.
      Interestingly, the inhibitory effect of hyaluronan on PDGF beta-receptor
      activation was not seen in the presence of the tyrosine phosphatase inhibitor
      pervanadate. Our observations suggest that hyaluronan suppresses PDGF beta
      receptor activation by recruiting a CD44-associated tyrosine phosphatase to the
      receptor.

PMID- 16809346
TI  - The Forkhead box M1 protein regulates the transcription of the estrogen receptor
      alpha in breast cancer cells.
AB  - In this study, we have identified the Forkhead transcription factor FoxM1 as a
      physiological regulator of estrogen receptor alpha (ERalpha) expression in breast
      carcinoma cells. Our survey of a panel of 16 different breast cell lines showed a
      good correlation (13/16) between FoxM1 expression and expression of ERalpha at
      both protein and mRNA levels. We have also demonstrated that ectopic expression
      of FoxM1 in two different estrogen receptor-positive breast cancer cell lines,
      MCF-7 and ZR-75-30, led to up-regulation of ERalpha expression at protein and
      transcript levels. Furthermore, treatment of MCF-7 cells with the MEK inhibitor
      U0126, which blocks ERK1/2-dependent activation of FoxM1, also repressed ERalpha
      expression. Consistent with this, silencing of FoxM1 expression in MCF-7 cells
      using small interfering RNA resulted in the almost complete abrogation of ERalpha
      expression. We also went on to show that FoxM1 can activate the transcriptional
      activity of human ERalpha promoter primarily through two closely located Forkhead
      response elements located at the proximal region of the ERalpha promoter.
      Chromatin immunoprecipitation and biotinylated oligonucleotide pulldown assays
      have allowed us to confirm these Forkhead response elements as important for
      FoxM1 binding. Further co-immunoprecipitation experiments showed that FoxO3a and
      FoxM1 interact in vivo. Together with the chromatin immunoprecipitation and
      biotinylated oligonucleotide pulldown data, the co-immunoprecipitation results
      also suggest the possibility that FoxM1 and FoxO3a cooperate to regulate ERalpha
      gene transcription.

PMID- 16809347
TI  - Differences in crystal and solution structures of the cytolethal distending toxin
      B subunit: Relevance to nuclear translocation and functional activation.
AB  - Cytolethal distending toxin (CDT) induces cell cycle arrest and apoptosis in
      eukaryotic cells, which are mediated by the DNA-damaging CdtB subunit. Here we
      report the first x-ray structure of an isolated CdtB subunit (Escherichia coli-II
      CdtB, EcCdtB). In conjunction with previous structural and biochemical
      observations, active site structural comparisons between free and holotoxin
      assembled CdtBs suggested that CDT intoxication is contingent upon holotoxin
      disassembly. Solution NMR structural and 15N relaxation studies of free EcCdtB
      revealed disorder in the interface with the CdtA and CdtC subunits (residues
      Gly233-Asp242). Residues Leu186-Thr209 of EcCdtB, which encompasses tandem
      arginine residues essential for nuclear translocation and intoxication, were also
      disordered in solution. In stark contrast, nearly identical well defined alpha
      helix and beta-strand secondary structures were observed in this region of the
      free and holotoxin CdtB crystallographic models, suggesting that distinct changes
      in structural ordering characterize subunit disassembly and nuclear localization
      factor binding functions.

PMID- 16809348
TI  - Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein
      glycans.
AB  - Inhibition of viruses at the stage of viral entry provides a route for
      therapeutic intervention. Because of difficulties in propagating hepatitis C
      virus (HCV) in cell culture, entry inhibitors have not yet been reported for this
      virus. However, with the development of retroviral particles pseudotyped with HCV
      envelope glycoproteins (HCVpp) and the recent progress in amplification of HCV in
      cell culture (HCVcc), studying HCV entry is now possible. In addition, these
      systems are essential for the identification and the characterization of
      molecules that block HCV entry. The lectin cyanovirin-N (CV-N) has initially been
      discovered based on its potent activity against human immunodeficiency virus.
      Because HCV envelope glycoproteins are highly glycosylated, we sought to
      determine whether CV-N has an antiviral activity against this virus. CV-N
      inhibited the infectivity of HCVcc and HCVpp at low nanomolar concentrations.
      This inhibition is attributed to the interaction of CV-N with HCV envelope
      glycoproteins. In addition, we showed that the carbohydrate binding property of
      CV-N is involved in the anti-HCV activity. Finally, CV-N bound to HCV envelope
      glycoproteins and blocked the interaction between the envelope protein E2 and
      CD81, a cell surface molecule involved in HCV entry. These data demonstrate that
      targeting the glycans of HCV envelope proteins is a promising approach in the
      development of antiviral therapies to combat a virus that is a major cause of
      chronic liver diseases. Furthermore, CV-N is a new invaluable tool to further
      dissect the early steps of HCV entry into host cells.

PMID- 16809349
TI  - Observations of unstained biological specimens using a low-energy, high
      resolution STEM.
AB  - Low-energy, high-resolution scanning transmission electron microscopy (STEM) is
      introduced as a convenient method for observing unstained biological specimens.
      By reducing the electron energy, the cross section for light elements becomes
      comparable to that of conventional electron microscopy observations. The STEM
      mode exhibited the advantage that the induced energy loss and charge build-up in
      the sample affected the image to a lesser extent than in the TEM or SEM mode.
      Furthermore, the efficiency of an STEM detector is high, and the total radiation
      damage can be reduced if thermal damage due to localized heating at a slow scan
      operation can be overcome. We applied this method for observations of biological
      samples that were in the form of thin slices, fine fibers and small particles.
      When the supporting film for samples is absent, the resolution and the contrast
      of STEM images can be maintained similar to SEM and TEM images, respectively.

PMID- 16809350
TI  - Acute hospital care for frail older people.

PMID- 16809351
TI  - A placebo-controlled, double-blind, randomized controlled trial of a natural
      killer cell stimulant (BioBran MGN-3) in chronic fatigue syndrome.
AB  - BACKGROUND: Previous research has suggested that natural killer (NK) cell
      activity may be reduced in patients with chronic fatigue syndrome (CFS). AIM: To
      evaluate the effectiveness of a putative NK cell stimulant, BioBran MGN-3, in
      reducing fatigue in CFS patients. DESIGN: Randomized, double-blind, placebo
      controlled trial. METHODS: We recruited 71 patients with CFS (according to the
      Centers for Disease Control 1994 criteria) attending an out-patient specialist
      CFS service. Participants were given oral BioBran MGN-3 for 8 weeks (2 g three
      times per day) or placebo equivalent. The primary outcome measure was the Chalder
      physical fatigue score. Self-reported fatigue measures, self-assessment of
      improvement, change in key symptoms, quality of life, anxiety and depression
      measures were also included. RESULTS: Data were complete in 64/71 patients. Both
      groups showed marked improvement over the study duration, but without significant
      differences. Mean improvement in the Chalder fatigue score (physical scale) was
      0.3 (95%CI -2.6 to 3.2) lower in the BioBran group. DISCUSSION: The findings do
      not support a specific therapeutic effect for BioBran in CFS. The improvement
      showed by both groups over time highlights the importance of placebo controls
      when evaluating interventions in CFS.

PMID- 16809352
TI  - Pigtail catheter drainage for secondary spontaneous pneumothorax.

PMID- 16809353
TI  - Cerebral venous sinus thrombosis in a tertiary care setting in India.

PMID- 16809354
TI  - Single measurements of glycaemic markers may lack stability over time.

PMID- 16809355
TI  - Many pathways are called! Many may be chosen!

PMID- 16809356
TI  - Novel roles of a local angiotensin-generating system in the carotid body.

PMID- 16809357
TI  - Contraction-initiated NO-dependent lymphatic relaxation: a self-regulatory
      mechanism in rat thoracic duct.
AB  - The objectives of this study were to evaluate the physiological importance of the
      flow and shear generated by phasic contractions of lymphatic vessels and the
      mechanisms responsible for the influences of such shear on lymphatic pumping.
      Lymphatic segments of the rat thoracic duct were isolated, cannulated and
      pressurized. The diastolic diameters were measured in phasically non-active
      segments. The diastolic and systolic diameters, half-relaxation time (HRT),
      contraction frequency, ejection fraction and fractional pump flow were determined
      in phasically active segments. Since imposed flow was excluded, flow and shear
      occurred only as a result of the intrinsic contractions in phasically active
      segments whereas in phasically non-active segments contraction-generated flow and
      shear were absent. The influences of incrementally increased transmural pressure
      (from 1 to 5 cmH(2)O) were examined in control conditions and after NO synthase
      blockade (l-NAME 10(-4) m) or cyclooxygenase blockade (indomethacin 10(-5) m).
      The spontaneous phasic contractions produced a flow-dependent diastolic
      relaxation. This reduction of the lymphatic tone is a regulatory mechanism that
      maintains pumping in thoracic duct in an energy-saving/efficient mode: it
      improves diastolic filling (enhanced lusitropy - lowering HRT), makes lymphatic
      contractions stronger (enhanced inotropy - higher contraction amplitude) and
      propels more fluid forward during each contraction (elevated ejection fraction)
      while decreasing contraction frequency (reduced chronotropy). The findings also
      demonstrated that the NO pathway, not the cyclooxygenase pathway is responsible
      for this reduction of lymphatic tone and is the prevailing pathway responsible
      for the self-regulatory adjustment of thoracic duct pumping to changes in lymph
      flow pattern.

PMID- 16809358
TI  - GABAA receptor subtype specific enhancement of inhibition in human motor cortex.
AB  - Inhibition is of fundamental importance to regulate activity in cortical
      circuits. Inhibition is mediated through a diversity of different interneurones
      and gamma-aminobutyric acid A receptor (GABA(A)R) subtypes. Here we employed
      paired-pulse transcranial magnetic stimulation (TMS) to measure short interval
      intracortical inhibition (SICI), a GABA(A)R-mediated inhibition in human motor
      cortex, to address the question of which GABA(A)R subtype is responsible for this
      form of inhibition. It has been shown that classical benzodiazepines (diazepam
      and lorazepam) have a non-selective affinity profile at different alpha-subunit
      bearing subtypes of the GABA(A)R while zolpidem has a 10-fold greater affinity to
      the alpha1-subunit-bearing GABA(A)R compared with those bearing the alpha2- or
      alpha3-subunit. We found that, in seven healthy subjects, a single oral dose of
      20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10
      mg of zolpidem did not change SICI. This dissociation occurred despite equal
      sedation by all three drugs, an alpha1-subunit GABA(A)R-mediated effect. The
      findings strongly suggest that SICI is not mediated by the alpha1-subunit-bearing
      subtype of the GABA(A)R but by those bearing either the alpha2- or alpha3
      subunit. This study represents an attempt by means of TMS to identify GABA(A)R
      subtype-specific action at the systems level of human cortex, a highly relevant
      issue because the different alpha-subunit-bearing subtypes of the GABA(A)R are
      differently involved in benzodiazepine-mediated effects such as sedation, amnesia
      or anxiolysis, in developmental cortical plasticity, and in neurological
      disorders such as epilepsy.

PMID- 16809359
TI  - Long-term intermittent hypoxia increases sympathetic activity and
      chemosensitivity during acute hypoxia in humans.
AB  - We determined the effects of 10 daily exposures of intermittent hypoxia (IH; 1 h
      day(-1); oxyhaemoglobin saturation = 80%) on muscle sympathetic nerve activity
      (MSNA, peroneal nerve) and the hypoxic ventilatory response (HVR) before, during
      and after an acute 20 min isocapnic hypoxic exposure. We also assessed the
      potential parallel modulation of the ventilatory and sympathetic systems
      following IH. Healthy young men (n = 11; 25 +/- 1 years) served as subjects and
      pre- and post-IH measures of MSNA were obtained on six subjects. The IH
      intervention caused HVR to significantly increase (pre-IH = 0.30 +/- 0.03; post
      IH = 0.61 +/- 0.12 l min(-1) %S(aO(2)) (-1)). During the 20 min hypoxic exposure
      sympathetic activity was significantly greater than baseline and remained above
      baseline after withdrawal of the hypoxic stimulus, even though oxyhaemoglobin
      saturation had normalized and ventilation and blood pressure had returned to
      baseline levels. When compared to the pre-IH trial, burst frequency increased (P
      < 0.01), total MSNA trended towards higher values (P = 0.06), and there was no
      effect on burst amplitude (P = 0.82) during the post-IH trial. Following IH the
      rise in MSNA burst frequency was strongly related to the change in HVR (r = 0.79,
      P < 0.05) suggesting that these sympathetic and ventilatory responses may have
      common central control.

PMID- 16809360
TI  - Malevolent lurkers no more: NMDA receptors come of age.

PMID- 16809361
TI  - Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal
      pigment epithelial cells to trigger release of ATP.
AB  - The photoreceptors lie between the inner retina and the retinal pigment
      epithelium (RPE). The release of glutamate by the phototoreceptors can signal
      changes in light levels to inner retinal neurons, but the role of glutamate in
      communicating with the RPE is unknown. Since RPE cells are known to release ATP,
      we asked whether glutamate could trigger ATP release from RPE cells and whether
      this altered cell signalling. Stimulation of the apical face of fresh bovine RPE
      eyecups with 100 mum NMDA increased ATP levels more than threefold, indicating
      that both receptors for NMDA and release of ATP occurred across the apical
      membrane of fresh RPE cells. NMDA increased ATP levels bathing cultured human
      ARPE-19 cells more than twofold, with NMDA receptor inhibitors MK-801 and d-AP5
      preventing this release. Blocking the glycine site of the NMDA receptor with 5,7
      dichlorokynurenic acid prevented ATP release from ARPE-19 cells. Release was also
      blocked by channel blocker NPPB and Ca(2+) chelator BAPTA, but not by cystic
      fibrosis transmembrane conductance regulator (CFTR) blocker glibenclamide or
      vesicular release inhibitor brefeldin A. Glutamate produced a dose-dependent
      release of ATP from ARPE-19 cells that was substantially inhibited by MK-801.
      NMDA triggered a rise in cell Ca(2+) that was blocked by MK-801, by the ATPase
      apyrase, by the P2Y(1) receptor antagonist MRS2179 and by depletion of
      intracellular Ca(2+) stores with thapsigargin. These results suggest that
      glutamate stimulates NMDA receptors on the apical membrane of RPE cells to
      release ATP. This secondary release can amplify the glutaminergic signal by
      increasing Ca(2+) inside RPE cells, and might activate Ca(2+)-dependent
      conductances. The interplay between glutaminergic and purinergic systems may thus
      be important for light-dependent interactions between photoreceptors and the RPE.

PMID- 16809363
TI  - Different levels of Ih determine distinct temporal integration in bursting and
      regular-spiking neurons in rat subiculum.
AB  - Pyramidal neurons in the subiculum typically display either bursting or regular
      spiking behaviour. Although this classification into two neuronal classes is well
      described, it is unknown how these two classes of neurons contribute to the
      integration of input to the subiculum. Here, we report that bursting neurons
      possess a hyperpolarization-activated cation current (I(h)) that is two-fold
      larger (conductance, 5.3 +/- 0.5 nS) than in regular-spiking neurons (2.2 +/- 0.6
      nS), whereas I(h) exhibits similar voltage-dependent and kinetic properties in
      both classes of neurons. Bursting and regular-spiking neurons display similar
      morphology. The difference in I(h) between the two classes of neurons is not
      responsible for the distinct firing patterns, as neither pharmacological blockade
      of I(h) nor enhancement of I(h) using a dynamic clamp affects the qualitative
      firing patterns. Instead, the difference in I(h) between bursting and regular
      spiking neurons determines the temporal integration of evoked synaptic input from
      the CA1 area. In response to stimulation at 50 Hz, bursting neurons, with a large
      I(h), show approximately 50% less temporal summation than regular-spiking
      neurons. The amount of temporal summation in both neuronal classes is equal after
      pharmacological blockade of I(h). A computer simulation model of a subicular
      neuron with the properties of either a bursting or a regular-spiking neuron
      confirmed the pivotal role of I(h) in temporal integration of synaptic input.
      These data suggest that in the subicular network, bursting neurons are better
      suited to discriminate the content of high-frequency input, such as that
      occurring during gamma oscillations, than regular-spiking neurons.

PMID- 16809362
TI  - Modulation of calcium wave propagation in the dendrites and to the soma of rat
      hippocampal pyramidal neurons.
AB  - Repetitive synaptic stimulation in the stratum radiatum (SR) evokes large
      amplitude Ca2+ waves in the thick apical dendrites of hippocampal CA1 pyramidal
      neurons. These waves are initiated by activation of metabotropic glutamate
      receptors (mGluRs), which mobilize inositol-1,4,5-trisphospate (IP3) and release
      Ca2+ from intracellular stores. We explored mechanisms that modulate the spatial
      properties of these waves. Higher stimulus current evoked waves of increasing
      spatial extent. Most waves did not propagate through the soma; the majority
      stopped close to the junction of the soma and apical dendrite. Pairing strong
      stimulation with one electrode and subthreshold stimulation with another
      (associative activation) extended the waves distally but failed to extend waves
      into the cell body. Pairing synaptic stimulation with backpropagating action
      potentials enhanced the likelihood of wave generation but did not extend the
      waves to the somatic region. Priming the stores with Ca2+ entry through voltage
      dependent channels modulated wave properties but did not extend them past the
      dendrites. These results are consistent with propagation failing due to the
      dilution of synaptically generated IP3 as it diffuses into the large volume of
      the soma (impedance mismatch). Synaptically activating waves in the presence of
      low concentrations of carbachol, which probably increased the tonic level of IP3
      throughout the cell, enhanced the extent of propagation and generated waves that
      invaded the soma, as long as low-affinity indicators were used to detect the
      [Ca2+]i changes. Consistent with this explanation direct injection of IP3 into
      the soma promoted wave propagation into this region. Ca2+ waves that propagated
      through the cell body were interesting because they did not fill the volume of
      the soma, but passed through the centre, often with large amplitude. These waves
      may be particularly effective in activating gene expression and protein
      synthesis.

PMID- 16809364
TI  - Sodium-calcium exchange does not require allosteric calcium activation at high
      cytosolic sodium concentrations.
AB  - The activity of the cardiac Na(+)-Ca(2+) exchanger (NCX1.1) is allosterically
      regulated by Ca(2+), which binds to two acidic regions in the cytosolically
      disposed central hydrophilic domain of the NCX protein. A mutation in one of the
      regulatory Ca(2+) binding regions (D447V) increases the half-activation constant
      (K(h)) for allosteric Ca(2+) activation from approximately 0.3 to > 1.8 microm.
      Chinese hamster ovary cells expressing the D447V exchanger showed little or no
      activity under physiological ionic conditions unless cytosolic [Ca(2+)] was
      elevated to > 1 microm. However, when cytosolic [Na(+)] was increased to 20 mm or
      more (using ouabain-induced inhibition of the Na(+),K(+)-ATPase or the ionophore
      gramicidin), cells expressing the D447V mutant rapidly accumulated Ca(2+) or
      Ba(2+) when the reverse (Ca(2+) influx) mode of NCX activity was initiated,
      although initial cytosolic [Ca(2+)] was < 100 nm. Importantly, the time course of
      Ca(2+) uptake did not display the lag phase that reflects allosteric Ca(2+)
      activation of NCX activity in the wild-type NCX1.1; indeed, at elevated [Na(+)],
      the D447V mutant behaved similarly to the constitutively active deletion mutant
      Delta(241-680), which lacks the regulatory Ca(2+) binding sites. In cells
      expressing wild-type NCX1.1, increasing concentrations of cytosolic Na(+) led to
      a progressive shortening of the lag phase for Ca(2+) uptake. The effects of
      elevated [Na(+)] developed rapidly and were fully reversible. The activity of the
      D447V mutant was markedly inhibited when phosphatidylinositol 4,5-bisphosphate
      (PIP2) levels were reduced. We conclude that when PIP2 levels are high, elevated
      cytosolic [Na(+)] induces a mode of exchange activity that does not require
      allosteric Ca(2+) activation.

PMID- 16809365
TI  - Strategies to unravel molecular codes essential for the development of meso
      diencephalic dopaminergic neurons.
AB  - Understanding the development of neuronal systems has become an important asset
      in the attempt to solve complex questions about neuropathology as found in
      Parkinson's disease, schizophrenia and other complex neuronal diseases. The
      development of anatomical and functional divergent structures in the brain is
      achieved by a combination of early anatomical patterning and highly coordinated
      neuronal migration and differentiation events. Fundamental to the existence of
      divergent structures in the brain is the early region-specific molecular
      programming. Neuronal progenitors located along the neural tube can still adapt
      many different identities. Their exact position in the developing brain, however,
      determines early molecular specification by region-specific signalling molecules.
      These signals determine time and region-specific expression of early regulatory
      genes, leading to neuronal differentiation. Here, we focus on a well-described
      neuronal group, the meso-diencephalic dopaminergic neurons, of which
      heterogeneity based on anatomical position could account for the difference in
      vulnerability of specific subgroups as observed in Parkinson's disease. The
      knowledge of their molecular coding helps us to understand how the meso
      diencephalic dopaminergic system is built and could provide clues that unravel
      mechanisms associated with the neuropathology in complex diseases such as
      Parkinson's disease.

PMID- 16809367
TI  - Recurrent inhibition of the bladder C fibre reflex in the cat and its response to
      naloxone.
AB  - Recurrent inhibition of the bladder C fibre reflex was studied in adult female
      cats anaesthetized with alpha-chloralose. Test reflexes were evoked by electrical
      stimulation of bladder Adelta and C afferents in the right pelvic nerve and were
      recorded from the proximal end of a small ipsilateral pelvic nerve branch,
      transected close to the bladder. Such test reflexes were consistently depressed
      by repetitive electrical stimulation of the contralateral bladder pelvic nerve
      (20 Hz, 20 s) at intensities sufficient to recruit axons of bladder preganglionic
      neurones. The inhibition could be evoked after transection of the left dorsal
      roots S1-S4 and the sympathetic supply to the bladder but was abolished by
      transection of the pelvic nerve central to the site of stimulation. Hence, it
      most likely involved central recurrent collaterals of antidromically activated
      bladder preganglionic neurones. The reflex suppression was quite considerable -
      maximal C fibre reflexes were reduced to a group mean of 25% (+/- 9% confidence
      interval) of their control size. The effect had a slow onset, requiring a few
      seconds of conditioning stimulation to be revealed, and was very long lasting
      (minutes). Naloxone (0.01-0.5 mg kg(-1) i.v.) abolished the recurrent inhibition
      of both the C fibre and Adelta bladder reflexes, while inhibition from afferents
      in the dorsal clitoris nerve remained unchanged. It is concluded that the
      segmental bladder C fibre reflex and the spino-ponto-spinal Adelta micturition
      reflex are both targets of recurrent inhibition from bladder parasympathetic
      preganglionic neurones and that the effect involves an enkephalinergic mechanism.

PMID- 16809368
TI  - Vestibular inputs elicit patterned changes in limb blood flow in conscious cats.
AB  - Previous experiments have demonstrated that the vestibular system contributes to
      regulating sympathetic nervous system activity, particularly the discharges of
      vasoconstrictor fibres. In the present study, we examined the physiological
      significance of vestibulosympathetic responses by comparing blood flow and
      vascular resistance in the forelimb and hindlimb during head-up tilt from the
      prone position before and after the removal of vestibular inputs through a
      bilateral vestibular neurectomy. Experiments were performed on conscious cats
      that were trained to remain sedentary on a tilt table during rotations up to 60
      deg in amplitude. Blood flow through the femoral and brachial arteries was
      recorded during whole-body tilt using perivascular probes; blood pressure was
      recorded using a telemetry system and vascular resistance was calculated from
      blood pressure and blood flow measurements. In vestibular-intact animals, 60 deg
      head-up tilt produced approximately 20% decrease in femoral blood flow and
      approximately 37% increase in femoral vascular resistance relative to baseline
      levels before tilt; similar effects were also observed for the brachial artery (
      approximately 25% decrease in blood flow and approximately 38% increase in
      resistance). Following the removal of vestibular inputs, brachial blood flow and
      vascular resistance during head-up tilt were almost unchanged. In contrast,
      femoral vascular resistance increased only approximately 6% from baseline during
      60 deg head-up rotation delivered in the first week after elimination of
      vestibular signals and approximately 16% in the subsequent 3-week period (as
      opposed to the approximately 37% increase in resistance that occurred before
      lesion). These data demonstrate that vestibular inputs associated with postural
      alterations elicit regionally specific increases in vascular resistance that
      direct blood flow away from the region of the body where blood pooling may occur.
      Thus, the data support the hypothesis that vestibular influences on the
      cardiovascular system serve to protect against the occurrence of orthostatic
      hypotension.

PMID- 16809366
TI  - Non-coding RNAs in the nervous system.
AB  - Increasing evidence suggests that the development and function of the nervous
      system is heavily dependent on RNA editing and the intricate spatiotemporal
      expression of a wide repertoire of non-coding RNAs, including micro RNAs, small
      nucleolar RNAs and longer non-coding RNAs. Non-coding RNAs may provide the key to
      understanding the multi-tiered links between neural development, nervous system
      function, and neurological diseases.

PMID- 16809369
TI  - Disinhibition of the cardiac limb of the arterial baroreflex in rat: a role for
      metabotropic glutamate receptors in the nucleus tractus solitarii.
AB  - The nucleus tractus solitarii (NTS) is the first site of integration for primary
      baroreceptor afferents, which release glutamate to excite second-order neurones
      through ionotropic receptors. In vitro studies indicate that glutamate may also
      activate metabotropic receptors (mGluRs) to modulate the excitability of NTS
      neurones at pre- and postsynaptic loci. We examined the functional role of
      metabotropic glutamate receptors (mGluRs) in modulating the baroreceptor reflex
      in the rat NTS. Using the working heart-brainstem preparation, the baroreflex was
      activated using brief pressor stimuli and the consequent cardiac (heart rate
      change) and non-cardiac sympathetic (T8-10 chain) baroreflex gains were obtained.
      Microinjections of glutamate antagonists were made bilaterally into the NTS at
      the site of termination of baroreceptor afferents. NTS microinjection of
      kynurenate (ionotropic antagonist) inhibited both the cardiac and sympathetic
      baroreflex gains (16 +/- 5% and 59 +/- 11% of control, respectively). The non
      selective mGluR antagonist MCPG produced a dose-dependent inhibition of the
      cardiac gain (30 +/- 3% of control) but not the sympathetic gain. Selective
      inhibitions of the cardiac gain were also seen with LY341495 and EGLU suggesting
      the response was mediated by group II mGluRs. This effect on cardiac gain
      involves attenuation of the parasympathetic baroreflex as it persists in the
      presence of atenolol. Prior NTS microinjection of bicuculline (GABA(A)
      antagonist) prevented the mGluR-mediated attenuation of the cardiac gain. These
      results are consistent with the reported presynaptic inhibition of GABAergic
      transmission by group II mGluRs in the NTS and constitute a plausible mechanism
      allowing selective feed-forward disinhibition to increase the gain of the cardiac
      limb of the baroreflex without changing the sympathoinhibitory component.

PMID- 16809370
TI  - Microarrays and the microscope: balancing throughput with resolution.
AB  - The cellular complexity of the brain is a major issue in the planning, execution
      and interpretation of microarray studies. Recent technical advances allow for
      high-throughput study of specific cell populations and circuits. Here we review
      representative examples of currently available methods that allow high resolution
      and specificity in brain microarray studies, while maintaining the goal of
      comprehensive, high-throughput analysis.

PMID- 16809371
TI  - Autoinhibitory control of the CaV1.2 channel by its proteolytically processed
      distal C-terminal domain.
AB  - Voltage-gated Ca(2+) channels of the Ca(V)1 family initiate excitation
      contraction coupling in cardiac, smooth, and skeletal muscle and are primary
      targets for regulation by the sympathetic nervous system in the 'fight-or-flight'
      response. In the heart, activation of beta-adrenergic receptors greatly increases
      the L-type Ca(2+) current through Ca(V)1.2 channels, which requires
      phosphorylation by cyclic AMP-dependent protein kinase (PKA) anchored via an A
      kinase anchoring protein (AKAP15). Surprisingly, the site of interaction of PKA
      and AKAP15 lies in the distal C-terminus, which is cleaved from the remainder of
      the channel by in vivo proteolytic processing. Here we report that the
      proteolytically cleaved distal C-terminal domain forms a specific molecular
      complex with the truncated alpha(1) subunit and serves as a potent autoinhibitory
      domain. Formation of the autoinhibitory complex greatly reduces the coupling
      efficiency of voltage sensing to channel opening and shifts the voltage
      dependence of activation to more positive membrane potentials. Ab initio
      structural modelling and site-directed mutagenesis revealed a binding interaction
      between a pair of arginine residues in a predicted alpha-helix in the proximal C
      terminal domain and a set of three negatively charged amino acid residues in a
      predicted helix-loop-helix bundle in the distal C-terminal domain. Disruption of
      this interaction by mutation abolished the inhibitory effects of the distal C
      terminus on Ca(V)1.2 channel function. These results provide the first functional
      characterization of this autoinhibitory complex, which may be a major form of the
      Ca(V)1 family Ca(2+) channels in cardiac and skeletal muscle cells, and reveal a
      unique ion channel regulatory mechanism in which proteolytic processing produces
      a more effective autoinhibitor of Ca(V)1.2 channel function.

PMID- 16809372
TI  - Physiological roles for amyloid beta peptides.
AB  - Alzheimer's disease is recognized post mortem by the presence of extracellular
      senile plaques, made primarily of aggregation of amyloid beta peptide (Abeta).
      This peptide has consequently been regarded as the principal toxic factor in the
      neurodegeneration of Alzheimer's disease. As such, intense research effort has
      been directed at determining its source, activity and fate, primarily with a view
      to preventing its formation or its biological activity, or promoting its
      degradation. Clearly, much progress has been made concerning its formation by
      proteolytic processing of the amyloid precursor protein, and its degradation by
      enzymes such as neprilysin and insulin degrading enzyme. The activities of Abeta,
      however, are numerous and yet to be fully elucidated. What is currently emerging
      from such studies is a diffuse but steadily growing body of data that suggests
      Abeta has important physiological functions and, further, that it should only be
      regarded as toxic when its production and degradation are imbalanced. Here, we
      review these data and suggest that physiological levels of Abeta have important
      physiological roles, and may even be crucial for neuronal cell survival. Thus,
      the view of Abeta being a purely toxic peptide requires re-evaluation.

PMID- 16809374
TI  - Anti-tuberculous therapy-induced crystal arthropathy.

PMID- 16809373
TI  - Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees
      C and 15 degrees C: implications for muscle fatigue.
AB  - Historically, an increase in intracellular H(+) (decrease in cell pH) was thought
      to contribute to muscle fatigue by direct inhibition of the cross-bridge leading
      to a reduction in velocity and force. More recently, due to the observation that
      the effects were less at temperatures closer to those observed in vivo, the
      importance of H(+) as a fatigue agent has been questioned. The purpose of this
      work was to re-evaluate the role of H(+) in muscle fatigue by studying the effect
      of low pH (6.2) on force, velocity and peak power in rat fast- and slow-twitch
      muscle fibres at 15 degrees C and 30 degrees C. Skinned fast type IIa and slow
      type I fibres were prepared from the gastrocnemius and soleus, respectively,
      mounted between a force transducer and position motor, and studied at 15 degrees
      C and 30 degrees C and pH 7.0 and 6.2, and fibre force (P(0)), unloaded
      shortening velocity (V(0)), force-velocity, and force-power relationships
      determined. Consistent with previous observations, low pH depressed the P(0) of
      both fast and slow fibres, less at 30 degrees C (4-12%) than at 15 degrees C
      (30%). However, the low pH-induced depressions in slow type I fibre V(0) and peak
      power were both significantly greater at 30 degrees C (25% versus 9% for V(0) and
      34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory
      effect of low pH on V(0) was unaltered by temperature, while for peak power the
      inhibition was reduced at 30 degrees C (37% versus 18%). The curvature of the
      force-velocity relationship was temperature sensitive, and showed a higher a/P(0)
      ratio (less curvature) at 30 degrees C. Importantly, at 30 degrees C low pH
      significantly depressed the ratio of the slow type I fibre, leading to less force
      and velocity at peak power. These data demonstrate that the direct effect of low
      pH on peak power in both slow- and fast-twitch fibres at near-in vivo
      temperatures (30 degrees C) is greater than would be predicted based on changes
      in P(0), and that the fatigue-inducing effects of low pH on cross-bridge function
      are still substantial and important at temperatures approaching those observed in
      vivo.

PMID- 16809375
TI  - Uterine artery Doppler in predicting pregnancy outcome in women with connective
      tissue disorders.

PMID- 16809376
TI  - Vagal nerve activity contributes to improve the efficiency of pulmonary gas
      exchange in hypoxic humans.
AB  - The aim of this study was to test our hypothesis that both phasic cardiac vagal
      activity and tonic pulmonary vagal activity, estimated as respiratory sinus
      arrhythmia (RSA) and anatomical dead space volume, respectively, contribute to
      improve the efficiency of pulmonary gas exchange in humans. We examined the
      effect of blocking vagal nerve activity with atropine on pulmonary gas exchange.
      Ten healthy volunteers inhaled hypoxic gas with constant tidal volume and
      respiratory frequency through a respiratory circuit with a respiratory analyser.
      Arterial partial pressure of O(2) (P(aO(2))) and arterial oxygen saturation
      (S(pO(2))) were measured, and alveolar-to-arterial P(O(2)) difference (D(A
      aO(2))) was calculated. Anatomical dead space (V(D,an)), alveolar dead space
      (V(D,alv)) and the ratio of physiological dead space to tidal volume
      (V(D,phys)/V(T)) were measured. Electrocardiogram was recorded, and the amplitude
      of R-R interval variability in the high-frequency component (RRIHF) was utilized
      as an index of RSA magnitude. These parameters of pulmonary function were
      measured before and after administration of atropine (0.02 mg kg(-1)). Decreased
      RRIHF (P < 0.01) was accompanied by decreases in P(aO(2)) and S(pO(2)) (P < 0.05
      and P < 0.01, respectively) and an increase in D(A-aO(2)) (P < 0.05). Anatomical
      dead space, V(D,alv) and V(D,phys)/V(T) increased (P < 0.01, P < 0.05 and P <
      0.01, respectively) after atropine administration. The blockade of the vagal
      nerve with atropine resulted in an increase in V(D,an) and V(D,alv) and a
      deterioration of pulmonary oxygenation, accompanied by attenuation of RSA. Our
      findings suggest that both phasic cardiac and tonic pulmonary vagal nerve
      activity contribute to improve the efficiency of pulmonary gas exchange in
      hypoxic conscious humans.

PMID- 16809377
TI  - Objective prioritization of positional candidate genes at a quantitative trait
      locus for pre-eclampsia on 2q22.
AB  - Pre-eclampsia/eclampsia (PE/E) is a common, serious medical disorder of human
      pregnancy. Familial association of PE/E has been recognized for decades, but the
      genetics are complex and poorly understood. In an attempt to identify PE/E
      susceptibility genes, we embarked on a positional cloning strategy using 34
      Australian and New Zealand PE/E pedigrees. An initial 10-cM resolution genome
      scan revealed a putative susceptibility locus spanning a broad region on
      chromosome 2 that overlaps an independently determined linkage signal seen in
      Icelandic PE pedigrees. Subsequent fine mapping using 25 additional short tandem
      repeat (STR) markers in this region and non-parametric multipoint linkage
      analysis did not change the overall position. Under a strict diagnosis of PE, we
      obtained significant evidence of linkage on 2q with a peak log-of-odds ratio
      score (LOD) of 3.43 near marker D2S151 at 155 cM. To prioritize positional
      candidate genes at the 2q locus for detailed analysis, we applied an objective
      prioritization strategy that integrates quantitative bioinformatics, assessment
      of differential gene expression and association analysis of single-nucleotide
      polymorphisms (SNPs). Highest priority was assigned to the activin receptor gene
      ACVR2. This gene also showed >10-fold differential gene expression in human
      decidual tissue from normotensive and PE individuals. We genotyped five known
      SNPs in this gene in our pedigrees and performed tests for association and
      linkage disequilibrium. One SNP (rs1424954) showed strong preliminary evidence of
      association with PE (P = 0.007), whereas two others (rs1364658 and rs1895694)
      exhibited nominal evidence (P < 0.05). Haplotype analysis revealed no additional
      association information. There was evidence of weak linkage disequilibrium among
      these SNPs. The highest observed LD occurred between the two strongest associated
      SNPs, suggesting that the observed signals may be the signature of an observed
      functional variant.

PMID- 16809378
TI  - The mechanisms involved in the action of metformin in regulating ovarian function
      in hyperandrogenized mice.
AB  - The aim of this study was to investigate the mechanisms by which N,N'
      dimethylbiguanide metformin (50 mg/100 g body weight (BW) in 0.05 ml of water,
      given orally with a cannula) prevents the ovarian disorders provoked by the
      hyperandrogenization with dehydroepiandrosterone (DHEA) in prepuberal BALB/c
      mice. The injection of DHEA (6 mg/100 g BW in 0.1 ml of oil) for 20 consecutive
      days re-creates a mouse model that resembles some aspects of the human polycystic
      ovary syndrome (PCOS). The treatment with DHEA increased ovarian oxidative stress
      because it enhanced lipid peroxidation (LPO) and diminished both catalase (CAT)
      activity and glutathione (GSH) content. Therefore, the treatment with DHEA
      diminished both ovarian nitric oxide synthase (NOS) activity and prostaglandin E
      (PGE) production. When metformin was administered together with DHEA, the ovarian
      GSH content, NOS activity and PGE production did not differ when compared with
      controls. However, metformin was not able to prevent the effect of DHEA on
      ovarian LPO or CAT activity. Finally, DHEA increased the ovarian protein
      expressions of inducible NOS (iNOS), inducible cyclooxygenase (COX2) and the
      phosphorylated AMP-dependent kinase alpha (AMPK-alpha) (Thr172). Metformin
      administered together with DHEA was able to prevent the increase of ovarian iNOS
      and COX2 expressions and to enhance the activation of phosphorylated AMPK-alpha
      expression.

PMID- 16809379
TI  - Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein
      accumulates in the epithelium and is released to the uterine fluid.
AB  - We have previously reported that endometrial mRNA expression of both tissue
      inhibitors of metalloproteinase-4 (TIMP-4) and matrix metalloproteinase-26 (MMP
      26) peaks in the early secretory phase, which implies a role in implantation. The
      objective of this study was to compare the distribution of TIMP-4 and MMP-26 in
      endometrial tissue and uterine fluid over the menstrual cycle. Endometrial tissue
      was analysed with in situ hybridization and immunohistochemistry to localize mRNA
      and protein for TIMP-4 and MMP-26 in the same set of samples. TIMP-4 mRNA was
      quantified in separated stromal and epithelial cells using real-time PCR. Uterine
      fluid was analysed with western blotting. TIMP-4 mRNA was exclusively localized
      to the stroma, whereas MMP-26 mRNA was expressed by epithelial cells. TIMP-4
      protein was only occasionally found in the stroma but was consistently present in
      granules of the apical part of luminal and glandular epithelial cells. TIMP-4,
      but not MMP-26, was demonstrated in uterine fluid. Thus, TIMP-4 is produced in
      the stroma only, secreted by stromal cells, taken up by epithelial cells,
      accumulated in apical granules and finally secreted to the uterine fluid. Maximal
      expression of MMP-26, and its strongest inhibitor TIMP-4, in the early and mid
      secretory phase suggests a role during implantation. MMP-26 is stored in
      epithelial cells in its active form, is not released spontaneously and is
      controlled by TIMP-4 in both stroma and uterine fluid.

PMID- 16809380
TI  - Peripapillary fundus perimetry in eyes with glaucoma.
AB  - AIMS: To evaluate, with fundus perimetry, the peripapillary differential light
      threshold (DLT) in eyes with glaucoma and ocular hypertension (OHT), and compare
      it with peripapillary retinal nerve fibre layer (RNFL) thickness. METHODS: 35
      glaucomatous, 29 OHT and 24 control eyes were included. Peripapillary DLT at 1
      degrees from the optic nerve head was quantified with fundus perimetry;
      peripapillary RNFL thickness was measured over the same area by optical coherence
      tomography. RESULTS: Mean (SD) peripapillary DLT was 19.2 (1.7), 17.6 (4.2) and
      10.1 (6.9) dB in control, OHT and glaucomatous eyes, respectively (p<0.001). Mean
      (SD) RNFL thickness was 98.4 (35.3), 83.9 (35.1) and 55.8 (28.2) microm,
      respectively (p<0.001). Mean peripapillary DLT showed higher sensitivity and
      specificity in differentiating the three groups compared with RNFL thickness.
      CONCLUSION: Progressive, significant reduction of peripapillary DLT was
      documented in OHT and glaucomatous eyes compared with controls (p<0.001). DLT
      reduction parallels RNFL reduction.

PMID- 16809381
TI  - Acute haemorrhagic conjunctivitis outbreak in the city of Fortaleza, northeast
      Brazil.
AB  - BACKGROUND/AIM: Between February and May 2003 an epidemic of acute haemorrhagic
      conjunctivitis affected more than 200 000 people in all five geographic regions
      of Brazil (north, south, midwestern, southeast, and northeast). The aim was to
      identify the aetiological agent and to describe clinical aspects of this outbreak
      in a group of patients treated at the ophthalmology department of the Hospital
      Walter Cantidio (OD-HWC) at the Universidade Federal do Ceara, in the city of
      Fortaleza, capital of the state of Ceara, northeastern Brazil. METHODS:
      Conjunctival swabs were collected from patients who spontaneously went to the
      laboratory of virology. Specimens were inoculated in HEp-2 and RD cell lines. The
      viral isolation was confirmed by performing reverse transcriptase polymerase
      chain reaction and indirect immunofluorescence assay. RESULTS: Viral
      conjunctivitis was diagnosed in 56 patients but only 24 of them allowed the
      collection of samples. Of 24 conjunctival swabs tested, 11 were positive for a
      variant of coxsackie virus A24 (CA24v) and one of the isolates reacted with anti
      adenovirus monoclonal antibodies. CONCLUSION: CA24v was confirmed as the
      aetiological agent of this outbreak of acute haemorrhagic conjunctivitis in the
      city of Fortaleza.

PMID- 16809382
TI  - Trefoil factor family 1, MUC5AC and human leucocyte antigen-DR expression by
      conjunctival cells in patients with glaucoma treated with chronic drugs: could
      these markers predict the success of glaucoma surgery?
AB  - AIMS: To evaluate conjunctival expression of trefoil factor family (TFF)1, MUC5AC
      and human leucocyte antigen (HLA)-DR in patients with glaucoma treated with
      topical drugs, and to determine whether these parameters can predict the outcome
      of glaucoma surgery. METHODS: 77 conjunctival impression cytology specimens were
      collected from 77 patients with glaucoma (66 receiving drops with preservative
      and 11 treated with preservative-free drops) and 43 controls. TFF1, MUC5AC and
      HLA-DR expression was analysed using flow cytometry. Trabeculectomy was performed
      in 56 patients; success was defined as an intraocular pressure (IOP) < or =15 mm
      Hg without any IOP-lowering drug at 6 months. RESULTS: The expression of TFF1,
      MUC5AC and HLA-DR was significantly higher in patients than in controls (p =
      0.01, 0.05 and 0.004, respectively). A higher expression of MUC5AC was found in
      patients treated with preserved drops than in those receiving unpreserved drops
      (p = 0.04). A higher MUC5AC expression and a lower HLA-DR expression was observed
      in successful glaucoma surgeries than in failures. CONCLUSIONS: TFF1 and MUC5AC
      secretions are probably a response to mild ocular surface changes caused by long
      term use of topical treatment. Their increased expression could be a predicting
      factor of further successful glaucoma surgery.

PMID- 16809383
TI  - Changing pattern of childhood blindness in Maharashtra, India.
AB  - AIM: To determine the causes of severe visual impairment and blindness in
      children in schools for the blind in Maharashtra, India. METHODS: Children aged
      <16 years with a visual acuity of <6/60 in the better eye, attending 35 schools
      for the blind were examined between 2002 and 2005, and causes were classified
      using the World Health Organization's system. RESULTS: 1985 students were
      examined, 1778 of whom fulfilled the eligibility criteria. The major causes of
      visual loss were congenital anomalies (microphthalmos or anophthalmos; 735,
      41.3%), corneal conditions (mainly scarring; 395, 22.2%), cataract or aphakia (n
      = 107, 6%), and retinal disorders (mainly dystrophies; n = 199, 11.2%). More than
      one third of children (34.5%) were blind from conditions which could have been
      prevented or treated, 139 of whom were referred for surgery. Low vision devices
      improved near-acuity in 79 (4.4%) children, and 72 (4%) benefited from
      refraction. No variation in causes by sex or region was observed. CONCLUSIONS:
      Congenital anomalies accounted for 41% of blindness, which is higher than in a
      similar study conducted 10 years ago. Corneal scarring seems to be declining in
      importance, low vision and optical services need to be improved, and research is
      needed to determine the aetiology of congenital anomalies.

PMID- 16809384
TI  - Ethnicity-specific prevalences of refractive errors vary in Asian children in
      neighbouring Malaysia and Singapore.
AB  - AIM: To compare the prevalences of refractive errors in Malay, Chinese and Indian
      children in Malaysia and Singapore. METHODS: Children aged 7-9 years from three
      schools in the Singapore Cohort study of the Risk factors for Myopia (n = 1962)
      and similarly aged children from a random cluster sample in the metropolitan
      Kuala Lumpur area in the Malaysia Refractive Error Study in Children (n = 1752)
      were compared. Cycloplegic autorefraction was conducted in both countries.
      RESULTS: The prevalence of myopia (spherical equivalent of at least -0.5 diopters
      (D) in either eye) was higher in Singapore Malays (22.1%) than in Malays in
      Malaysia (9.2%; 95% confidence interval (CI) 11.2 to 14.7; p<0.001). Similarly,
      Singapore Chinese (40.1%) had higher prevalences than Malaysian Chinese (30.9%;
      95% CI 1.5 to 16.9). Singapore Indians had a higher prevalence (34.1%) than
      Malaysian Indians (12.5%; 95% CI 17.4 to 25.9). The multivariate odds ratio of
      astigmatism (cylinder at least 0.75 D in either eye) in Singapore Malays compared
      with Malaysian Malays was 3.47 (95% CI 2.79 to 4.32). Ethnicity-specific
      hyperopia rates did not differ in Singapore and Malaysia. CONCLUSION: The
      ethnicity-specific prevalences of myopia in Singapore Malays, Chinese and Indians
      are higher than those in Malaysian Malays, Chinese and Indians. As Malays,
      Chinese and Indians in Malaysia have genetic make-up similar to that of Malays,
      Chinese and Indians in Singapore, environmental factors may contribute to the
      higher myopia rates.

PMID- 16809386
TI  - Pathway analysis using random forests classification and regression.
AB  - MOTIVATION: Although numerous methods have been developed to better capture
      biological information from microarray data, commonly used single gene-based
      methods neglect interactions among genes and leave room for other novel
      approaches. For example, most classification and regression methods for
      microarray data are based on the whole set of genes and have not made use of
      pathway information. Pathway-based analysis in microarray studies may lead to
      more informative and relevant knowledge for biological researchers. RESULTS: In
      this paper, we describe a pathway-based classification and regression method
      using Random Forests to analyze gene expression data. The proposed methods allow
      researchers to rank important pathways from externally available databases,
      discover important genes, find pathway-based outlying cases and make full use of
      a continuous outcome variable in the regression setting. We also compared Random
      Forests with other machine learning methods using several datasets and found that
      Random Forests classification error rates were either the lowest or the second
      lowest. By combining pathway information and novel statistical methods, this
      procedure represents a promising computational strategy in dissecting pathways
      and can provide biological insight into the study of microarray data.
      AVAILABILITY: Source code written in R is available from
      http://bioinformatics.med.yale.edu/pathway-analysis/rf.htm.

PMID- 16809385
TI  - Relationship between macular hole size and the potential benefit of internal
      limiting membrane peeling.
AB  - AIM: To investigate the relationship between the size of macular holes and the
      possible benefit of internal limiting membrane (ILM) peeling. METHODS: 84
      consecutive cases of idiopathic macular hole followed up for at least 3 months
      were included in this retrospective study. Surgery comprised pars plana
      vitrectomy, peeling of any epiretinal membrane, 17% C2F6 (hexafluoroethane) gas
      filling and 10 days of positioning. 36 eyes had ILM peeling. The main outcome
      measure was the macular hole closure rate checked by optical coherence
      tomography. RESULTS: The overall postoperative closure rate was 90.5%. For
      macular holes > or =400 microm in diameter, the rate was 100% with ILM peeling
      versus 73.3% without (p = 0.015). For smaller macular holes, the rates were 100%
      in both groups. Postoperative gain in visual acuity was not significantly
      different in eyes with ILM peeling and those without. CONCLUSIONS: ILM peeling
      does not seem to be useful for macular hole <400 mum in diameter. Its likely
      benefit has to be investigated for larger macular hole sizes, for which the
      failure rate is higher.

PMID- 16809387
TI  - A mixture model-based discriminate analysis for identifying ordered transcription
      factor binding site pairs in gene promoters directly regulated by estrogen
      receptor-alpha.
AB  - MOTIVATION: To detect and select patterns of transcription factor binding sites
      (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha
      (ERalpha), we developed an innovative mixture model-based discriminate analysis
      for identifying ordered TFBS pairs. RESULTS: Biologically, our proposed new
      algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha
      target promoters (P-value < 0.001). The up-regulated targets significantly (P
      value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP,
      USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly
      (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and
      (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate
      analysis can simultaneously perform TFBS pattern recognition, TFBS pattern
      selection, and target class prediction; such integrative power cannot be achieved
      by current methods. AVAILABILITY: The software is available on request from the
      authors. CONTACT: lali@iupui.edu SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 16809388
TI  - ET viewer: an application for predicting and visualizing functional sites in
      protein structures.
AB  - SUMMARY: The Evolutionary Trace Viewer (ETV) provides a one-stop environment in
      which to run, visualize and interpret Evolutionary Trace (ET) predictions of
      functional sites in protein structures. ETV is implemented using Java to run
      across different operating systems using Java Web Start technology. AVAILABILITY:
      The ETV is available for download from our website at
      http://mammoth.bcm.tmc.edu/traceview/index.html. This webpage also links to
      sample trace results and a user manual that describes ET Viewer functions in
      detail.

PMID- 16809389
TI  - Effects of replacing the unreliable cDNA microarray measurements on the disease
      classification based on gene expression profiles and functional modules.
AB  - MOTIVATION: Microarrays datasets frequently contain a large number of missing
      values (MVs), which need to be estimated and replaced for subsequent data mining.
      The focus of the paper is to study the effects of different MV treatments for
      cDNA microarray data on disease classification analysis. RESULTS: By analyzing
      five datasets, we demonstrate that among three kinds of classifiers evaluated in
      this study, support vector machine (SVM) classifiers are robust to varied MV
      imputation methods [e.g. replacing MVs by zero, K nearest-neighbor (KNN)
      imputation algorithm, local least square imputation and Bayesian principal
      component analysis], while the classification and regression tree classifiers are
      sensitive in terms of classification accuracy. The KNNclassifiers built on
      differentially expressed genes (DEGs) are robust to the varied MV treatments, but
      the performances of the KNN classifiers based on all measured genes can be
      significantly deteriorated when imputing MVs for genes with larger missing rate
      (MR) (e.g. MR > 5%). Generally, while replacing MVs by zero performs relatively
      poor, the other imputation algorithms have little difference in affecting
      classification performances of the SVM or KNN classifiers. We further demonstrate
      the power and feasibility of our recently proposed functional expression profile
      (FEP) approach as means to handle microarray data with MVs. The FEPs, which are
      derived from the functional modules that are enriched with sets of DEGs and thus
      can be consistently identified under varied MV treatments, achieve precise
      disease classification with better biological interpretation. We conclude that
      the choice of MV treatments should be determined in context of the later
      approaches used for disease classification. The suggested exclusion criterion of
      ignoring the genes with larger MR (e.g. >5%), while justifiable for some
      classifiers such as KNN classifiers, might not be considered as a general rule
      for all classifiers.

PMID- 16809390
TI  - Eicosapentapeptide repeats (EPRs): novel repeat proteins specific to flowering
      plants.
AB  - In this report, we describe a novel tandem peptide repeat protein,
      Eicosapentapeptide repeat (EPR), which occurs notably only in flowering plants.
      The EPRs are characterized by a 25 amino acid repeat unit,
      X(2)CX(4)CX(10)CX(2)HGGG, repeated 10 times tandemly. Sequence search revealed
      that the repeat motif is highly conserved across its occurrence. EPRs are
      predicted to exist as quasi-globular stable structures owing to highly conserved
      amino acid positions and potential disulfide bridges. Proteins containing EPRs
      are predicted to be located in chloroplasts; non-enzymatic and peptide or DNA
      binding in molecular function; and they are possibly involved in transcription
      regulation.

PMID- 16809391
TI  - Domain organization within repeated DNA sequences: application to the study of a
      family of transposable elements.
AB  - MOTIVATION: The analysis of repeated elements in genomes is a fascinating domain
      of research that is lacking relevant tools for transposable elements (TEs), the
      most complex ones. The dynamics of TEs, which provides the main mechanism of
      mutation in some genomes, is an essential component of genome evolution. In this
      study we introduce a new concept of domain, a segmentation unit useful for
      describing the architecture of different copies of TEs. Our method extracts
      occurrences of a terminus-defined family of TEs, aligns the sequences, finds the
      domains in the alignment and searches the distribution of each domain in
      sequences. After a classification step relative to the presence or the absence of
      domains, the method results in a graphical view of sequences segmented into
      domains. RESULTS: Analysis of the new non-autonomous TE AtREP21 in the model
      plant Arabidopsis thaliana reveals copies of very different sizes and various
      combinations of domains which show the potential of our method. AVAILABILITY:
      DomainOrganizer web page is available at www.irisa.fr/symbiose/DomainOrganizer/.

PMID- 16809392
TI  - PDQ Wizard: automated prioritization and characterization of gene and protein
      lists using biomedical literature.
AB  - SUMMARY: PDQ Wizard automates the process of interrogating biomedical references
      using large lists of genes, proteins or free text. Using the principle of linkage
      through co-citation biologists can mine PubMed with these proteins or genes to
      identify relationships within a biological field of interest. In addition, PDQ
      Wizard provides novel features to define more specific relationships, highlight
      key publications describing those activities and relationships, and enhance
      protein queries. PDQ Wizard also outputs a metric that can be used for
      prioritization of genes and proteins for further research. AVAILABILITY: PDQ
      Wizard is freely available from http://www.gti.ed.ac.uk/pdqwizard/.

PMID- 16809393
TI  - An iterative refinement algorithm for consistency based multiple structural
      alignment methods.
AB  - MOTIVATION: Multiple STructural Alignment (MSTA) provides valuable information
      for solving problems such as fold recognition. The consistency-based approach
      tries to find conflict-free subsets of alignments from a pre-computed all-to-all
      Pairwise Alignment Library (PAL). If large proportions of conflicts exist in the
      library, consistency can be hard to get. On the other hand, multiple structural
      superposition has been used in many MSTA methods to refine alignments. However,
      multiple structural superposition is dependent on alignments, and a superposition
      generated based on erroneous alignments is not guaranteed to be the optimal
      superposition. Correcting errors after making errors is not as good as avoiding
      errors from the beginning. Hence it is important to refine the pairwise library
      to reduce the number of conflicts before any consistency-based assembly. RESULTS:
      We present an algorithm, Iterative Refinement of Induced Structural alignment
      (IRIS), to refine the PAL. A new measurement for the consistency of a library is
      also proposed. Experiments show that our algorithm can greatly improve T-COFFEE
      performance for less consistent pairwise alignment libraries. The final multiple
      alignment outperforms most state-of-the-art MSTA algorithms at assembling 15
      transglycosidases. Results on three other benchmarks showed that the algorithm
      consistently improves multiple alignment performance. AVAILABILITY: The C++ code
      of the algorithm is available upon request.

PMID- 16809394
TI  - SNPeffect v2.0: a new step in investigating the molecular phenotypic effects of
      human non-synonymous SNPs.
AB  - Single nucleotide polymorphisms (SNPs) constitute the most fundamental type of
      genetic variation in human populations. About 75 000 of these reported variations
      cause an amino acid change in the translated protein. An important goal in
      genomic research is to understand how this variability affects protein function,
      and whether or not particular SNPs are associated to disease susceptibility.
      Accordingly, the SNPeffect database uses sequence- and structure-based
      bioinformatics tools to predict the effect of non-synonymous SNPs on the
      molecular phenotype of proteins. SNPeffect analyses the effect of SNPs on three
      categories of functional properties: (1) structural and thermodynamic properties
      affecting protein dynamics and stability (2) the integrity of functional and
      binding sites and (3) changes in posttranslational processing and cellular
      localization of proteins. The search interface of the database can be used to
      search specifically for polymorphisms that are predicted to cause a change in one
      of these properties. Now based on the Ensembl human databases, the SNPeffect
      database has been remodeled to better fit an automatically updatable structure.
      The current edition holds the molecular phenotype of 74 567 nsSNPs in 23 426
      proteins. AVAILABILITY: SNPeffect can be accessed through
      http://snpeffect.vib.be.

PMID- 16809395
TI  - Parallel multifactor dimensionality reduction: a tool for the large-scale
      analysis of gene-gene interactions.
AB  - Parallel multifactor dimensionality reduction is a tool for large-scale analysis
      of gene-gene and gene-environment interactions. The MDR algorithm was redesigned
      to allow an unlimited number of study subjects, total variables and variable
      states, and to remove restrictions on the order of interactions being analyzed.
      In addition, the algorithm is markedly more efficient, with approximately 150
      fold decrease in runtime for equivalent analyses. To facilitate the processing of
      large datasets, the algorithm was made parallel. AVAILABILITY: Parallel MDR is
      freely available for non-commercial research institutions. For full details see
      http://chgr.mc.vanderbilt.edu/ritchielab/pMDR. An open-source version of MDR
      software is available at http://www.epistasis.org.

PMID- 16809396
TI  - GEL: a novel genotype calling algorithm using empirical likelihood.
AB  - MOTIVATION: Preliminary results on the data produced using the Affymetrix large
      scale genotyping platforms show that it is necessary to construct improved
      genotype calling algorithms. There is evidence that some of the existing
      algorithms lead to an increased error rate in heterozygous genotypes, and a
      disproportionately large rate of heterozygotes with missing genotypes. Non-random
      errors and missing data can lead to an increase in the number of false
      discoveries in genetic association studies. Therefore, the factors that need to
      be evaluated in assessing the performance of an algorithm are the missing data
      (call) and error rates, but also the heterozygous proportions in missing data and
      errors. RESULTS: We introduce a novel genotype calling algorithm (GEL) for the
      Affymetrix GeneChip arrays. The algorithm uses likelihood calculations that are
      based on distributions inferred from the observed data. A key ingredient in
      accurate genotype calling is weighting the information that comes from each probe
      quartet according to the quality/reliability of the data in the quartet, and
      prior information on the performance of the quartet. AVAILABILITY: The GEL
      software is implemented in R and is available by request from the corresponding
      author at nicolae@galton.uchicago.edu.

PMID- 16809397
TI  - The human X chromosome is enriched for germline genes expressed in premeiotic
      germ cells of both sexes.
AB  - The role of X-chromosomal genes in spermatogenesis has been subject to a number
      of studies in different organisms. Recently, it was proposed that the X
      chromosome has a predominant role in premeiotic stages of mammalian
      spermatogenesis. We analyzed the expression of a representative set of 17 X
      linked and 48 autosomal germline-restricted genes in different stages of human
      germ cell development. In accordance with data from other species, we show that
      the human X chromosome is indeed significantly enriched for genes activated in
      premeiotic stages of spermatogenesis. In contrast to recent studies, however, we
      found that expression of these genes is not restricted to spermatogenesis, but is
      activated in oogenesis as well. Furthermore, we show that activation of this
      subset of genes merely depends on demethylation of their promoter regions.
      Moreover, our data suggest that genes activated in premeiotic stages of
      gametogenesis are sex-indifferent and are regulated by DNA methylation. Gene
      activation patterns involved in spermatocyte-specific differentiation, in
      contrast, appear to be initiated not before entry into meiosis and underlie a
      more complex regulation, presumably involving specific transcription factors
      and/or chromatin remodeling mechanisms.

PMID- 16809398
TI  - Immunofluorometric point-of-care assays for the detection of acute coronary
      syndrome-related noncomplexed pregnancy-associated plasma protein A.
AB  - BACKGROUND: We recently reported that the pregnancy-associated plasma protein A
      (PAPP-A) form specifically related to acute coronary syndromes (ACS) is not
      complexed with the proform of eosinophil major basic protein (proMBP). The aim of
      this study was to develop rapid point-of-care immunoassays for the measurement of
      the noncomplexed PAPP-A. METHODS: We developed immunofluorometric noncompetitive
      dry-reagent assays for total PAPP-A with 2 PAPP-A subunit-specific monoclonal
      antibodies and for PAPP-A/proMBP complex with 1 PAPP-A subunit-specific antibody
      and 1 proMBP subunit-specific antibody. The concentration of noncomplexed PAPP-A
      was determined as the difference of the results obtained with the 2 assays.
      RESULTS: The assays were linear from 0.5 to 300 mIU/L. The analytical detection
      limit and functional detection limit (CV <20%) were 0.18 mIU/L and 0.27 mIU/L for
      total PAPP-A assay and 0.23 mIU/L and 0.70 mIU/L for PAPP-A/proMBP assay,
      respectively. The total assay imprecisions were <10%, and recoveries were 88%
      107% for both assays. The mean difference (95% limits of agreement) between the
      new total PAPP-A assay and a previously reported total PAPP-A assay was -3.2% (
      45.7% to 39.3%; n = 546; P = 0.0019). In serum samples from 159 non-ACS
      individuals, median concentrations (interquartile range) were 2.42 (1.14) mIU/L
      for total PAPP-A, 2.20 (1.18) mIU/L for PAPP-A/proMBP, and 0.18 (0.63) mIU/L for
      noncomplexed PAPP-A. Total PAPP-A and PAPP-A/proMBP, but not noncomplexed PAPP-A,
      correlated with age (r = 0.290, P = 0.0002; r = 0.230, P = 0.0035; r = 0.075, P =
      0.3483, respectively). CONCLUSIONS: The new assays described revealed that
      noncomplexed PAPP-A is found only in negligible amounts in non-ACS samples.

PMID- 16809399
TI  - Antibody arrays: technical considerations and clinical applications in cancer.
AB  - Antibody arrays represent one of the high-throughput techniques that are able to
      detect multiple proteins simultaneously. One of the main advantages of this
      technology over other proteomic approaches is that the identities of the measured
      proteins are known or can be readily characterized, allowing a biological
      interpretation of the results. Features such as lower sample volume and antibody
      concentration requirements, higher format versatility, and reproducibility
      support the increasing use of antibody arrays in cancer research. Clinical
      applications include disease marker discovery for diagnosis, prognosis, and drug
      response, characterization of signaling and protein pathways, and modifications
      associated with disease development and progression. This report presents an
      overview of technical issues of the main antibody array formats and various
      applications in cancer research. Antibody arrays are high-throughput tools that
      improve the functional characterization of molecular bases for disease.
      Furthermore, identification and validation of protein expression patterns,
      characteristic of cancer progression, and tumor subtypes may intervene and
      improve tailored therapies in the clinical management of cancer patients.

PMID- 16809400
TI  - Factors that influence cancer patients' overall perceptions of the quality of
      care.
AB  - OBJECTIVE: This study outlines predictors of cancer patients' overall perceptions
      of the quality of care. DESIGN AND SETTING: Our sample included 2790 patients who
      received cancer care services during 2004 in 15 comprehensive cancer programmes
      across Ontario, Canada. Patients were classified into three groups: those
      receiving both chemotherapy and radiotherapy (n = 752), those receiving only
      chemotherapy (n = 1044), and those receiving only radiotherapy (n = 994). An
      ordinal logistic regression model for each patient group was performed to
      determine which variables most affected the probabilities of the patients'
      overall evaluations of the quality of care. Potential control variables were
      patients' age, sex, type of cancer, self-assessed health, and who completed the
      survey. RESULTS: Among seven common predictors of the overall quality perception
      across the three models, four should be of particular interest because patients
      perceived them as relatively problematic aspects of care. These are 'was informed
      about follow-up care after completing treatment', 'knew next step in care', 'knew
      who to go to with questions', and 'providers were aware of test results'. These
      predictors explained between 25 and 34% of the variance (depending on the model)
      of the overall perception of quality. The explanatory power of these predictors
      did not change across sex and age group. 'Self-assessed health' was the only
      control variable that remained in all three models. CONCLUSIONS: From a practical
      perspective, improvement efforts are best focused on factors that are strong
      predictors as well as on those for which there is a low score. Thus, on the basis
      of this study, practitioners' improvement efforts might be constructively focused
      on the four predictors mentioned above.

PMID- 16809401
TI  - Do women change their drinking behaviors while trying to conceive? An opportunity
      for preconception counseling.
AB  - BACKGROUND: Prenatal alcohol exposure is a leading cause of preventable mental
      retardation and developmental disabilities, including fetal alcohol syndrome.
      Current medical guidelines recommend that no alcohol should be consumed over the
      period of conception and throughout pregnancy. Although the majority of women
      reduce alcohol consumption when they realize they are pregnant, this recognition
      may not occur until well into the first trimester, potentially impacting
      embryonic development. OBJECTIVES: To describe and assess changes in patterns of
      women's alcohol use between the preconception, pre-pregnancy recognition and post
      pregnancy recognition time periods. Secondly, to describe characteristics of
      women consuming any alcohol and those binge drinking during pre- and post
      pregnancy recognition periods. METHODS: Computer assisted telephone interviews
      were conducted with 1042 women who had recently delivered a baby in urban
      Alberta, Canada. Differences in consumption patterns between time periods were
      analyzed using analysis of variance and Chi-square tests. Characteristics of
      those drinking both before and after pregnancy recognition were analyzed using
      logistic regression. RESULTS: Eighty percent of women reported alcohol
      consumption pre-conceptually, 50% pre-pregnancy recognition and 18% post
      pregnancy recognition. Binge drinking was reported by 32%, 11% and 0% for
      preconception, pre-pregnancy recognition and post-pregnancy recognition periods,
      respectively. Alcohol consumption patterns (i.e., the mean number of drinks per
      drinking day and week) did not differ significantly between preconception and pre
      pregnancy recognition periods but did significantly drop after pregnancy
      recognition (p<0.001). Alcohol use during the period of pre-pregnancy recognition
      was higher among those not planning a pregnancy, not using assisted reproductive
      technology, of higher income, without a history of miscarriage, who were
      Caucasian, and who used tobacco. Binge drinking was higher among women not
      planning a pregnancy, those who used tobacco, and those with low self-esteem.
      Women continuing to drink small amounts of alcohol after pregnancy recognition
      were more likely to be between the ages of 30-39 years, be Caucasian and use
      tobacco. CONCLUSION: Preconception and "well-women" counseling strategies would
      be improved by increasing the emphasis on the risks of alcohol use during periods
      when pregnancy can occur.

PMID- 16809403
TI  - Nonlinear dynamics of blood pressure variability after caffeine consumption.
AB  - OBJECTIVES: The occurrence of continuous blood pressure (BP) fluctuations is an
      intrinsic feature of the cardiovascular system and is related to complex
      cardiovascular mechanisms and environmental stimulations or daily habits such as
      coffee drinking. The aim of this study was to investigate the effect of caffeine
      on indices expressing the complex and "chaotic" nonlinear characteristics of BP
      variability. DESIGN: Fourteen healthy subjects consumed 240 mg of caffeine or
      placebo according to a randomized, double-blind, crossover design. Continuous
      radial pressure waveforms were recorded by applanation tonometry at baseline and
      at 30, 60, 90 and 120 minutes after ingestion of caffeine or placebo. METHODS:
      Approximate entropy (ApEn) was determined to assess BP irregularity. Detrended
      fluctuation analysis was also used to quantify the fractal correlation properties
      of the BP data by estimating the scaling (self-similarity) exponent alpha.
      Analysis of variance for repeated measurements was used to detect significant
      changes in the measured variables at 30, 60, 90 and 120 minutes after ingestion
      of caffeine or placebo. RESULTS: BP fluctuations demonstrated high regularity and
      predictability as indicated by the low values of ApEn (0.2 +/- 0.3), and they
      remained unchanged after caffeine ingestion. In contrast, the long-term scaling
      exponent alpha of the BP time series was significantly increased from 0.99 to
      1.04 (p=0.01) after caffeine ingestion, while the placebo induced no significant
      change. CONCLUSIONS: Caffeine induced greater "randomness" in BP fluctuations,
      possibly by triggering cardiovascular mechanisms that could not be directly
      specified but should be investigated in future studies.

PMID- 16809402
TI  - Amoebicidal activity of milk, apo-lactoferrin, sIgA and lysozyme.
AB  - OBJECTIVES: To identify amoebicidal components in human milk and the effect of
      iron on the amoebicidal activity. DESIGN: Investigation in axenic cultures of
      Entamoeba histolytica trophozoites. METHODS: Amoebas were treated with 5%-20% of
      human, bovine and swine milk, with 10% of human milk fractions (i.e., casein,
      proteins except casein and fat) or with 1 mg/ml of human milk apo-lactoferrin,
      human secretory immunoglobulin type A (sIgA) and chicken egg-white lysozyme
      (i.e., purified proteins). Milk proteins were detected using immunoblot. Confocal
      microscopy was used to define the interaction of milk proteins (100 microM each)
      and amoebas. Experiments were done at least three times in triplicate, and mean
      and standard deviations were calculated. RESULTS: Human and bovine milk were
      amoebicidal showing a concentration-dependent effect. The amoebicidal effect was
      increased in the absence of iron. Milk protein fractions, with the exception of
      casein, were the components responsible for the amoebicidal activity found. Apo
      lactoferrin, sIgA and lysozyme were identified in the amoebicidal milk protein
      fraction. Apo-lactoferrin showed the major amoebicidal effect. These proteins,
      either alone or in combination, showed a killing effect on the trophozoites. They
      bound to the amoebic membrane causing cell rounding, lipid disruption and damage.
      CONCLUSIONS: Milk proteins such as apo-lactoferrin, sIgA and lysozyme are able to
      kill Entamoeba histolytica trophozoites. This study confirms the importance of
      feeding breast milk to newborns.

PMID- 16809404
TI  - Lipid-rich plaque masquerading as a coronary thrombus.
AB  - A 43-year-old woman presented with exertional chest pressure. Right coronary
      angiography showed a clear filling defect. Intravascular ultrasound revealed a
      plaque with 80% stenosis and a large lipid pool. Therefore, a stent was placed,
      and the patient became angina-free. Lipid-rich plaques are a cause of
      angiographic filling defects. Intravascular ultrasound is an integral part of
      coronary artery evaluation.

PMID- 16809405
TI  - Genetic diagnosis and testing in clinical practice.
AB  - Genetic testing is defined as "the analysis of human DNA, RNA, chromosomes,
      proteins and certain metabolites in order to detect heritable disease-related
      genotypes, mutations, phenotypes or karyotypes for clinical purposes." This
      article focuses on diagnostic and predictive genetic testing. The latter includes
      presymptomatic testing, which identifies individuals who are expected to become
      ill in the future and predisposition testing, which identifies those who are at
      increased risk of becoming ill. Decisions regarding genetic testing must be based
      not only on the analytic accuracy, availability and cost of the test, but on the
      clinical utility as well, including the sensitivity, specificity and
      interpretability of results. Clinical information, including the medical and
      family history and the findings of the physical examination, is vital for the
      selection of appropriate diagnostic tests, as well as the interpretation of the
      results. Presymptomatic genetic testing is a very personal choice that should
      only be made after the patient has had sufficient counseling to develop an
      understanding of the risks and benefits of the test and is able to make an
      informed decision. The same principle applies to predisposition testing; however,
      additional factors, such as the probability of a positive result, the likelihood
      that the disease will actually develop in those with positive results, the effect
      on the management of the index patient, the effects on family members, the risk
      of false reassurance if the result is negative or the potential for loss of hope
      if it is positive, all contribute to the assessment of risk versus benefit.
      Clinical evaluation and counseling of the patient who is at risk for a genetic
      disorder are labor intensive but essential for the selection and interpretation
      of genetic tests.

PMID- 16809406
TI  - The emerging role of pituitary tumor transforming gene in tumorigenesis.
AB  - Pituitary tumor transforming gene (PTTG) is a newly discovered oncogene, and
      serves as a marker of malignancy grades in several forms of cancer, particularly
      endocrine malignancies such as pituitary adenomas. PTTG appears also to have a
      role in the genesis of some types of cancer. Also known as a human form of
      securin, PTTG is an anaphase inhibitor that prevents premature chromosome
      separation through inhibition of separase activity; hence, its degradation is
      required to start anaphase. Through this important function, PTTG participates in
      several key cellular events such as mitosis, cell cycle progression, DNA repair
      and apoptosis. The physiological importance of PTTG is indicated by the study of
      PTTG-null mice that have cell growth abnormalities in testis and pancreatic beta
      cells. Overexpression of PTTG has been observed in thyroid and colon cancers. In
      addition, 90% of pituitary adenomas overexpress PTTG, qualifying it as the best
      available marker for this disease. Although the exact mechanism is unknown, PTTG
      participates in the pathogenesis of various tumors, including pituitary tumors,
      by inducing aneuploidy and upregulating FGF-2, a potent mitogenic and angiogenic
      factor. Various growth factors, nuclear factors and hormones regulate PTTG
      expression in different tumor cells, which could be important to understand in
      order to obtain insight into the tumorigenic and tumor progression process. Here,
      we review the current knowledge of the biological and pathophysiological roles of
      PTTG.

PMID- 16809407
TI  - The use of intravenous and aerosolized polymyxins for the treatment of infections
      in critically ill patients: a review of the recent literature.
AB  - Intravenous and aerosolized polymyxins are being used increasingly, especially in
      the critical care setting, for treating patients with infections due to multidrug
      resistant Gram-negative bacteria, mainly Acinetobacter baumannii and Pseudomonas
      aeruginosa. Recent literature suggests that intravenous colistin and polymyxin B
      have acceptable effectiveness for the treatment of patients with bacteremia, as
      well as infections of various systems and organs, including pneumonia,
      bacteremia, skin and soft tissue, and urinary tract infections. Although data
      from recent studies have suggested that the toxicity of intravenous polymyxins is
      probably less than reported in the older literature, caution should be taken to
      monitor the renal function of patients who receive these antibiotics.

PMID- 16809408
TI  - Skewed Th1 responses caused by excessive expression of Txk, a member of the Tec
      family of tyrosine kinases, in patients with Behcet's disease.
AB  - Behcet's disease (BD) is characterized by recurrent attacks of uveitis, oral
      aphtha, genital ulcers and skin lesions. The etiology and pathogenesis of BD are
      largely unknown. It has been reported that excessive Th1 cell function is
      involved in the pathogenesis of BD. Previously, we found that Txk, a member of
      the Tec family of tyrosine kinases, acts as a Th1 cell-specific transcription
      factor that is involved in the effector function of Th1 cells. Thus, we studied
      Th1 cytokine production and Txk expression of T-lymphocytes in patients with BD.
      Peripheral blood lymphocytes produced excessive Th1-associated cytokines
      including interferon-gamma (IFN-gamma) and interleukin (IL)-12 in patients with
      BD. Circulating CD3+ and purified CD4+ T cells expressed excessive Txk protein.
      The extent of IFN-gamma production by the lymphocytes correlated with the
      expression of Txk protein in the immunoblotting analysis. The majority of cells
      infiltrating into the skin lesions of patients with BD expressed IFN-gamma. IL-12
      and IL-18 were found in the mononuclear cell aggregates in the skin and
      intestinal lesions of those with BD. Lymphocytes accumulating in the skin and
      intestinal lesions expressed higher levels of Txk as compared with other Th2
      associated diseases. IFN-gamma, IL-18 and IL-12 detected in skin lesions may
      induce preferential development of Th1 cells in patients with BD. Collectively,
      Th1 cells expressing Txk and Th1-associated cytokines may play a critical role in
      the development of skin and intestinal lesions in patients with BD. This review
      may serve as a reminder of the importance of excessive Th1 cell function in the
      pathogenesis of BD and may contribute to the discovery of new molecular targets
      for the development of a specific therapeutic strategy for BD.

PMID- 16809409
TI  - Statin treatment and reduced risk of pneumonia in patients with diabetes.
AB  - BACKGROUND: Recent prognostic studies have shown that previous treatment with
      statins is associated with a better outcome in patients admitted to hospital with
      pneumonia. Because of an increased risk of pneumonia in patients with diabetes,
      we assessed the effects of statin use on the occurrence of pneumonia in adult
      diabetic patients. METHODS: All patients with a diagnosis of diabetes (types 1
      and 2) enlisted in the UK General Practice Research Database between 1 June 1987
      and 21 January 2001 were included. A case-control study was performed with cases
      defined as patients with a first recorded diagnosis of pneumonia. For each case
      up to four controls were matched by age, sex, practice, and index date. Patients
      were classified as current users when the index date was between the start and
      end date of statin treatment. Conditional multiple logistic regression analysis
      was used to estimate the strength of the association between statin treatment and
      the occurrence of pneumonia. RESULTS: Statins were used in 1.1% of 4719 cases and
      in 2.1% of 15 322 matched controls (crude odds ratio (OR) 0.51, 95% CI 0.37 to
      0.68). After adjusting for potential confounders, treatment with statins was
      associated with a significant reduction in the risk of pneumonia (adjusted OR
      0.49, 95% CI 0.35 to 0.69). The association was consistent among relevant
      subgroups (cardiovascular diseases, pulmonary diseases) and independent of the
      use of other prescription drugs. CONCLUSIONS: The use of statins is associated
      with a considerable reduction in the risk of pneumonia in diabetic patients. In
      addition to lowering the risk of cardiovascular disease, statins may be useful in
      preventing respiratory infections.

PMID- 16809410
TI  - In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by
      inhibiting the production and activation of TGF-beta in the lung.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis is a devastating disorder for which
      there is no effective treatment. Transforming growth factor (TGF)-beta plays a
      critical role in provoking fibrosis. Interleukin (IL)-10 is a potent
      immunosuppressive cytokine but its effect on the fibrosing process is unclear. A
      study was undertaken to examine whether IL-10 affects the production and
      activation of TGF-beta and thus can attenuate the fibrosis. METHODS: Mice were
      given an intratracheal injection of bleomycin. On day 1 or 14, IL-10 gene was
      delivered by rapid intravenous injection of Ringer's solution containing plasmid.
      Two weeks after the plasmid injection the mice were examined for fibrosis. The
      effect of IL-10 on TGF-beta production by alveolar macrophages was assessed.
      RESULTS: Even when delivered during the fibrosing phase, IL-10 gene significantly
      suppressed the pathological findings, hydroxyproline content, and production of
      both active and total forms of TGF-beta1 in the lung. Immunohistochemical
      analyses showed that alveolar macrophages were one of the major sources of TGF
      beta1 and IL-10 diminished the intensity of the staining. IL-10 also suppressed
      the expression of alphaV beta6 integrin, a molecule that plays an important role
      in TGF-beta activation, on lung epithelial cells. Alveolar macrophages from
      bleomycin injected mice produced TGF-beta1 spontaneously ex vivo, which was
      significantly suppressed by treatment of the mice in vivo or by treatment of the
      explanted macrophages ex vivo with IL-10. CONCLUSION: IL-10 suppresses the
      production and activation of TGF-beta in the lung and thus attenuates pulmonary
      fibrosis, even when delivered in the chronic phase.

PMID- 16809411
TI  - Functional KCa3.1 K+ channels are required for human lung mast cell migration.
AB  - BACKGROUND: Mast cell recruitment and activation are critical for the initiation
      and progression of inflammation and fibrosis. Mast cells infiltrate specific
      structures in many diseased tissues such as the airway smooth muscle (ASM) in
      asthma. This microlocalisation of mast cells is likely to be key to disease
      pathogenesis. Human lung mast cells (HLMC) express the Ca2+ activated K+ channel
      K(Ca)3.1 which modulates mediator release, and is proposed to facilitate the
      retraction of the cell body during migration of several cell types. A study was
      undertaken to test the hypothesis that blockade of K(Ca)3.1 would attenuate HLMC
      proliferation and migration. METHODS: HLMC were isolated and purified from lung
      material resected for bronchial carcinoma. HLMC proliferation was assessed by
      cell counts at various time points following drug exposure. HLMC chemotaxis was
      assayed using standard Transwell chambers (8 microm pore size). Ion currents were
      measured using the single cell patch clamp technique. RESULTS: K(Ca)3.1 blockade
      with triarylmethane-34 (TRAM-34) did not inhibit HLMC proliferation and
      clotrimazole had cytotoxic effects. In contrast, HLMC migration towards the
      chemokine CXCL10, the chemoattractant stem cell factor, and the supernatants from
      tumour necrosis factor alpha stimulated asthmatic ASM was markedly inhibited with
      both the non-selective K(Ca)3.1 blocker charybdotoxin and the highly specific
      K(Ca)3.1 blocker TRAM-34 in a dose dependent manner. Although K(Ca)3.1 blockade
      inhibits HLMC migration, K(Ca)3.1 is not opened by the chemotactic stimulus,
      suggesting that it must be involved downstream of the initial receptor-ligand
      interactions. CONCLUSIONS: Since modulation of K(Ca)3.1 can inhibit HLMC
      chemotaxis to diverse chemoattractants, the use of K(Ca)3.1 blockers such as TRAM
      34 could provide new therapeutic strategies for mast cell mediated diseases such
      as asthma.

PMID- 16809412
TI  - Cough in the community: a cross sectional survey and the relationship to
      gastrointestinal symptoms.
AB  - BACKGROUND: The prevalence and severity of chronic cough in the community is
      uncertain. In a large population of representative normal subjects, we explored
      the relationship between self-reported cough severity and frequency, and factors
      known to be related to the aetiology of chronic cough. In particular, we have
      examined the relative association between cough and symptoms of gastrointestinal
      disease. METHODS: A cross-sectional survey was undertaken in 36 general practices
      with subjects randomly selected from practice computer databases. Baseline
      lifestyle and demographic characteristics were recorded. Participants were asked
      how often in the previous 2 months they had experienced bouts or spasms of
      coughing. Cough symptom status was dichotomised into symptomatic using a cut off
      of bouts or spasms of coughing at a frequency of between once a week and once a
      day or above. Gastrointestinal data were collected using validated methodology.
      RESULTS: Questionnaires were sent to 6416 subjects and 4003 (62%) responded. The
      prevalence of chronic cough was 12%, and was severe in 7%. Following multivariate
      analysis, regurgitation (OR 1.71; 99% CI 1.20 to 2.45) and irritable bowel
      syndrome (OR 2.00; 99% CI 1.47 to 2.72) were strong predictors of cough. Smoking
      (OR 1.61; 99% CI 1.18 to 2.19), declining social class (OR 1.63; 99% CI 1.04 to
      2.57), and quality of life at baseline (OR 1.63; 99% CI 1.13 to 2.35) were also
      significantly associated. CONCLUSION: Chronic cough is a common symptom in the
      general population. Its strong association with gastrointestinal disease may have
      aetiological significance.

PMID- 16809413
TI  - Epidemiology of organising pneumonia in Iceland.
AB  - BACKGROUND: Cryptogenic organising pneumonia (COP) has also been called
      idiopathic bronchiolitis obliterans organising pneumonia. In secondary organising
      pneumonia (SOP) the causes can be identified or it occurs in a characteristic
      clinical context. The aim of this study was to determine the incidence and
      epidemiological features of COP and SOP nationwide in Iceland over an extended
      period. METHODS: A retrospective study of organising pneumonia (OP) in Iceland
      over 20 years was conducted and the epidemiology and survival were studied. All
      pathological reports of patients diagnosed with or suspected of having COP or SOP
      in the period 1984-2003 were identified and the pathology samples were re
      evaluated using strict diagnostic criteria. RESULTS: After re-evaluation, 104
      patients fulfilled the diagnostic criteria for OP (58 COP and 46 SOP). The mean
      annual incidence of OP was 1.97/100 000 population (1.10/100 000 for COP and
      0.87/100 000 for SOP). The mean age at diagnosis was 67 years with a wide age
      range. The most common causes of death were lung diseases other than OP, and only
      one patient died from OP. Patients with OP had a lower rate of survival than the
      general population, but there was no statistical difference between COP and SOP.
      CONCLUSIONS: The incidence of OP is higher than previously reported, suggesting
      that OP needs to be considered as a diagnosis more often than has been done in
      the past.

PMID- 16809414
TI  - Respiratory symptoms and 30 year mortality from obstructive lung disease and
      pneumonia.
AB  - BACKGROUND: As little is known about the long term relationship between
      respiratory symptoms and mortality from non-malignant respiratory diseases, a
      study was undertaken to investigate the predictive value of respiratory symptoms
      and symptom load for mortality from obstructive lung disease (OLD) and pneumonia
      in the long term in a Norwegian population. METHODS: In 1972, 19 998 persons aged
      15-70 years living in Oslo were randomly selected for a respiratory survey. The
      response rate was 89%. All were followed for 30 years. The association between
      cough, asthma-like symptoms, two levels of dyspnoea on exercise, a symptom score,
      and mortality from OLD and pneumonia were investigated separately for men and
      women by multivariable analyses, with adjustment for age, occupational exposure
      to air pollution, and smoking habits. RESULTS: OLD accounted for 43% and
      pneumonia for 50% of all deaths from respiratory causes. In men the hazard ratio
      for mortality from OLD varied from 4.0 (95% confidence interval (CI) 2.4 to 6.5)
      for cough to 9.6 (95% CI 5.1 to 18.3) for severe dyspnoea, and in women from 5.1
      (95% CI 2.3 to 11.3) for moderate dyspnoea to 13.0 (95% CI 6.0 to 28.3) for
      severe dyspnoea. The symptom score was strongly predictive of death from OLD in a
      dose-response manner. CONCLUSIONS: There is a significant, positive, strong
      association between respiratory symptoms and 30 year mortality from OLD. The
      association between respiratory symptoms and mortality from pneumonia is weaker
      and not significant.

PMID- 16809415
TI  - Smokers with airway obstruction are more likely to quit smoking.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD), usually caused by
      tobacco smoking, is one of the leading causes of morbidity and mortality. Smoking
      cessation at an early stage of the disease usually stops further progression. A
      study was undertaken to determine if diagnosis of airway obstruction was
      associated with subsequent success in smoking cessation, as advised by a
      physician. METHODS: 4494 current smokers (57.4% men) with a history of at least
      10 pack-years of smoking were recruited from 100 000 subjects screened by
      spirometric testing for signs of airway obstruction. At the time of screening all
      received simple smoking cessation advice. 1177 (26.2%) subjects had airway
      obstruction and were told that they had COPD and that smoking cessation would
      halt rapid progression of their lung disease. No pharmacological treatment was
      proposed. After 1 year all subjects were invited for a follow up visit. Smoking
      status was assessed by history and validated by exhaled carbon monoxide level.
      RESULTS: Nearly 70% attended a follow up visit (n = 3077): 61% were men, mean
      (SD) age was 52 (10) years, mean (SD) tobacco exposure 30 (17) pack-years, and
      33.3% had airway obstruction during the baseline examination. The validated
      smoking cessation rate in those with airway obstruction was 16.3% compared with
      12.0% in those with normal spirometric parameters (p = 0.0003). After correction
      for age, sex, nicotine dependence, number of cigarettes smoked daily, and lung
      function, success in smoking cessation was predicted by lower lung function,
      lower nicotine dependence, and lower tobacco exposure. CONCLUSIONS: Simple
      smoking cessation advice combined with spirometric testing resulted in good 1
      year cessation rates, especially in subjects with airway obstruction.

PMID- 16809416
TI  - Long term effects of azithromycin in patients with cystic fibrosis: A double
      blind, placebo controlled trial.
AB  - BACKGROUND: Macrolides display immunomodulatory effects that may be beneficial in
      chronic inflammatory pulmonary diseases. The aim of the study was to document
      whether long term use of azithromycin may be associated with respiratory benefits
      in young patients with cystic fibrosis. METHODS: A multicentre, randomised,
      double blind, placebo controlled trial was conducted from October 2001 to June
      2003. The criteria for enrollment were age older than 6 years and forced
      expiratory volume in 1 second (FEV1) of 40% or more. The active group received
      either 250 mg or 500 mg (body weight < or > or =40 kg) of oral azithromycin three
      times a week for 12 months. The primary end point was change in FEV1. RESULTS:
      Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV1 85 (22)%
      predicted were randomised: 40 in the azithromycin group and 42 in the placebo
      group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative
      change in FEV1 at month 12 did not differ significantly between the two groups.
      The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p
      < 0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio
      0.37 (95% CI 0.22 to 0.63), p < 0.0001), and the number of additional courses of
      oral antibiotics were significantly reduced in the azithromycin group regardless
      of the infectious status (count ratio 0.55 (95% CI 0.36 to 0.85), p < 0.01). No
      severe adverse events were reported. CONCLUSION: Long term use of low dose
      azithromycin in young patients with cystic fibrosis has a beneficial effect on
      lung disease expression, even before infection with Pseudomonas aeruginosa.

PMID- 16809417
TI  - Empirical treatment with a fluoroquinolone delays the treatment for tuberculosis
      and is associated with a poor prognosis in endemic areas.
AB  - BACKGROUND: A study was conducted to evaluate the effect of the empirical use of
      fluoroquinolones on the timing of antituberculous treatment and the outcome of
      patients with tuberculosis in an endemic area. METHODS: All patients with culture
      confirmed tuberculosis aged > or =14 years diagnosed between July 2002 and
      December 2003 were included and their medical records were reviewed. RESULTS:
      Seventy nine (14.4%) of the 548 tuberculosis patients identified received a
      fluoroquinolone (FQ group), 218 received a non-fluoroquinolone antibiotic (AB
      group), and 251 received no antibiotics before antituberculous treatment. Fifty
      two (65.8%) experienced clinical improvement after fluoroquinolone use. In the FQ
      group the median interval from the initial visit to starting antituberculous
      treatment was longer than in the AB group and in those who received no
      antibiotics (41 v 16 v 7 days), and the prognosis was worse (hazard ratio 6.88
      (95% CI 1.84 to 25.72)). More patients in the FQ and AB groups were aged >65
      years (53.2% and 61.0% v 31.5%), had underlying disease (53.2% and 46.8% v
      34.3%), and were hypoalbuminaemic (67.2% and 64.9% v 35.1%). Of the nine
      mycobacterial isolates obtained after fluoroquinolone use from nine patients
      whose initial isolates were susceptible to ofloxacin, one (11.1%) was resistant
      to ofloxacin (after fluoroquinolone use for 7 days). Independent factors for a
      poor prognosis included empirical fluoroquinolone use, age >65, underlying
      disease, hypoalbuminaemia, and lack of early antituberculous treatment.
      CONCLUSIONS: 14.4% of our patients with tuberculosis received a fluoroquinolone
      before the diagnosis. With a 34 day delay in antituberculous treatment and more
      frequent coexistence of underlying disease and hypoalbuminaemia, empirical
      fluoroquinolone treatment was associated with a poor outcome. Mycobacterium
      tuberculosis isolates could obtain ofloxacin resistance within 1 week.

PMID- 16809418
TI  - Association of tumour necrosis factor alpha promoter haplotype with chronic
      pancreatitis.

PMID- 16809419
TI  - Inhibition of macrophage function prevents intestinal inflammation and
      postoperative ileus in rodents.
AB  - BACKGROUND: Abdominal surgery results in a molecular and cellular inflammatory
      response in the intestine, leading to postoperative ileus. It was hypothesised
      that resident macrophages within the intestinal muscularis have an important role
      in this local inflammation. AIMS: To investigate whether chemical or genetic
      depletion of resident muscularis macrophages would lead to a reduction in the
      local inflammation and smooth-muscle dysfunction. METHODS: Two rodent models were
      used to deplete and inactivate macrophages: (1) a rat model in which resident
      macrophages were depleted by chlodronate liposomes; (2) a model of mice with
      osteopetrosis mice, completely lacking the resident muscularis macrophages, used
      as an additional genetic approach. Animals with normal or altered intestinal
      macrophages underwent surgical intestinal manipulation. The inflammatory response
      was investigated by quantitative reverse transcriptase-polymerase chain reaction
      for mRNA of MIP-1alpha, interleukin (IL)1beta, IL6, intracellular adhesion
      molecule 1 (ICAM-1) and monocyte chemotractant protein 1 (MCP)-1 in the isolated
      small bowel muscularis. In addition, muscularis whole mounts were used for
      histochemical and immunohistochemical analysis to quantify leucocyte infiltration
      and detect cytokine expression. Subsequently, in vitro muscle contractility and
      in vivo gastrointestinal transit were measured. RESULTS: Both models resulted in
      markedly decreased expression of MIP-1alpha, IL1beta, IL6, ICAM-1 and MCP-1 after
      manipulation compared with controls. In addition to this decrease in inflammatory
      mediators, recruitment of leucocytes into the muscularis was also diminished.
      Macrophage-altered animals had near normal in vitro jejunal circular muscle
      function and gastrointestinal transit despite surgical manipulation. CONCLUSIONS:
      Resident intestinal muscularis macrophages are initially involved in inflammatory
      responses resulting in postoperative ileus. Depletion and inactivation of the
      muscularis macrophage network prevents postoperative ileus.

PMID- 16809420
TI  - Plasminogen fragment K1-5 improves survival in a murine hepatocellular carcinoma
      model.
AB  - BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) remains
      poor, and new alternative treatments are needed. AIMS: To comparatively test the
      angiostatic and antitumour effects of adenoviral gene transfer of angiostatin
      (PlgK1-4, amino acids 1-440) and full kringles 1-5 (PlgK1-5, amino acids 1-546)
      in a model of subcutaneously transferred HCC in mice. METHODS: PlgK1-4 and PlgK1
      5 were generated from human WtPlg cDNA and used for adenovirus construction.
      Vector function and angiostatic effects were confirmed in vitro and in vivo.
      Antitumoral efficacies of intratumoral vector injections were studied in a model
      of subcutaneously transferred HCC model. RESULTS: Cell supernatants containing
      PlgK1-4 and PlgK1-5 reduced endothelial tube formation in vitro by about 30%,
      whereas WtPlg exerted no inhibitory effect. Endothelial cell infiltration in vivo
      was decreased by about 60%, but not in AdWtPlg-treated animals. Intratumoral
      treatment of subcutaneous HCC tumours inhibited growth by 40% for AdPlgK1-4 and
      63% for AdPlgK1-5 in surviving mice 12 days after initiation of treatment,
      whereas treatment with AdWtPlg even led to accelerated growth. Although PlgK1-4
      and PlgK1-5 have similar inhibitory effects on intratumoral microvessels, PlgK1-5
      markedly improved the survival time compared with PlgK1-4. CONCLUSION: PlgK1-5
      and PlgK1-4 effectively inhibited HCC growth. As PlgK1-5 could also prolong the
      survival time, inducing complete tumour elimination in half of the AdPlgK1-5
      treated mice, PlgK1-5 might be the most potential plasminogen fragment for
      treatment of experimental HCC.

PMID- 16809421
TI  - Artificial neural network is superior to MELD in predicting mortality of patients
      with end-stage liver disease.
AB  - BACKGROUND: Despite its accuracy, the model for end-stage liver disease (MELD),
      currently adopted to determine the prognosis of patients with liver cirrhosis,
      guide referral to transplant programmes and prioritise the allocation of donor
      organs, fails to predict mortality in a considerable proportion of patients.
      AIMS: To evaluate the possibility to better predict 3-month liver disease-related
      mortality of patients awaiting liver transplantation using an artificial neural
      network (ANN). PATIENTS AND METHODS: The ANN was constructed using data from 251
      consecutive people with cirrhosis listed for liver transplantation at the Liver
      Transplant Unit, Bologna, Italy. The ANN was trained to predict 3-month survival
      on 188 patients, tested on the remaining 63 (internal validation group) unknown
      by the system and finally on 137 patients listed for liver transplantation at the
      King's College Hospital, London, UK (external cohort). Predictions of survival
      obtained with ANN and MELD on the same datasets were compared using areas under
      receiver-operating characteristic (ROC) curves (AUC). RESULTS: The ANN performed
      significantly better than MELD both in the internal validation group (AUC = 0.95
      v 0.85; p = 0.032) and in the external cohort (AUC = 0.96 v 0.86; p = 0.044).
      CONCLUSIONS: The ANN measured the mortality risk of patients with cirrhosis more
      accurately than MELD and could better prioritise liver transplant candidates,
      thus reducing mortality in the waiting list.

PMID- 16809422
TI  - Enhanced expression of hepatocyte growth factor activator inhibitor type 2
      related small peptide at the invasive front of colon cancers.
AB  - BACKGROUND: Hepatocyte growth factor activator inhibitor type 2-related small
      peptide (H2RSP) is a small nuclear protein abundantly expressed in the
      gastrointestinal epithelium. However, its functions remain unknown. AIMS: To
      investigate the expression and localisation of H2RSP in normal, injured and
      neoplastic human intestinal tissue. METHODS: Immunohistochemical examination and
      in situ hybridisation for H2RSP were performed using normal and diseased
      intestinal specimens. Its subcellular localisation and effects on the cellular
      proliferation and invasiveness were examined using cultured cells. RESULTS: In
      the normal intestine, H2RSP was observed in the nuclei of surface epithelial
      cells and this nuclear localisation was impaired in regenerating epithelium. In
      vitro, the nuclear translocation of H2RSP was observed along with increasing
      cellular density, and an overexpression of H2RSP resulted in a reduced growth
      rate and enhanced invasiveness. H2RSP expression was down regulated in well
      differentiated colorectal adenocarcinomas. However, a marked up regulation of the
      cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive
      front. These cells showed low MIB-1 labelling, an enhanced p16 expression and
      nuclear beta-catenin. The number of H2RSP-positive cells in the invasive front of
      well-differentiated adenocarcinomas was considerably higher in the cases with
      lymph node metastases than in node-negative ones. CONCLUSION: In the normal
      intestine, the nuclear accumulation of H2RSP is a marker of differentiated
      epithelial cells. Although H2RSP was down regulated in colorectal
      adenocarcinomas, a paradoxical up regulation was observed in actively invading
      carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a
      marker of invasive phenotype of well-differentiated colon cancers.

PMID- 16809423
TI  - Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob
      disease in transgenic human prion protein 129 heterozygous mice.
AB  - All neuropathologically confirmed cases of variant Creutzfeldt-Jakob disease
      (vCJD), characterized by abundant florid plaques and type 4 disease-related prion
      protein (PrP(Sc)) in the brain, have been homozygous for methionine at
      polymorphic residue 129 of PRNP. The distinctive neuropathological and molecular
      phenotype of vCJD can be faithfully recapitulated in Prnp-null transgenic mice
      homozygous for human PrP M129 but not V129, where a distinct prion strain is
      propagated. Here we model susceptibility of 129MV heterozygotes, the most common
      PRNP genotype, in transgenic mice and show that, remarkably, propagation of type
      4 PrP(Sc) was not associated with characteristic vCJD neuropathology. Depending
      on the source of the inoculum these mice can develop four distinct disease
      phenotypes after challenge with bovine spongiform encephalopathy (BSE) prions or
      vCJD (human-passaged BSE) prions. vCJD-challenged mice had higher attack rates of
      prion infection than BSE-challenged recipients. These data argue that human PRNP
      129 heterozygotes will be more susceptible to infection with vCJD prions than to
      cattle BSE prions and may present with a neuropathological phenotype distinct
      from vCJD.

PMID- 16809424
TI  - Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis.
AB  - Protein phosphatases have very recently emerged as important targets for chemical
      biology and medicinal chemistry research, and new phosphatase inhibitor classes
      are in high demand. The underlying frameworks of natural products represent the
      evolutionarily selected fractions of chemical space explored by nature so far and
      meet the criteria of relevance to nature and biological prevalidation most
      crucial to inhibitor development. We refer to synthesis efforts and compound
      collection development based on these criteria as biology-oriented synthesis. For
      the discovery of phosphatase inhibitor classes by means of this approach, four
      natural product-derived or -inspired medium-sized compound collections were
      synthesized and investigated for inhibition of the tyrosine phosphatases VE-PTP,
      Shp-2, PTP1B, MptpA, and MptpB and the dual-specificity phosphatases Cdc25A and
      VHR. The screen yielded four unprecedented and selective phosphatase inhibitor
      classes for four phosphatases with high hit rates. For VE-PTP and MptpB the first
      inhibitors were discovered. These results demonstrate that biology-oriented
      synthesis is an efficient approach to the discovery of new compound classes for
      medicinal chemistry and chemical biology research that opens up new opportunities
      for the study of phosphatases, which may lead to the development of new drug
      candidates.

PMID- 16809425
TI  - Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant
      hippocampal neurons lacking junctophilins.
AB  - Junctional membrane complexes (JMCs) composed of the plasma membrane and
      endoplasmic/sarcoplasmic reticulum seem to be a structural platform for channel
      crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the
      sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle
      cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice
      lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired
      memory. Electrophysiological experiments indicated that the activation of small
      conductance Ca(2+)-activated K(+) channels responsible for afterhyperpolarization
      in hippocampal neurons requires endoplasmic reticulum Ca(2+) release through
      ryanodine receptors, triggered by NMDA receptor-mediated Ca(2+) influx. We
      propose that in JP-DKO neurons lacking afterhyperpolarization, the functional
      communications between NMDA receptors, ryanodine receptors, and small-conductance
      Ca(2+)-activated K(+) channels are disconnected because of JMC disassembly.
      Moreover, JP-DKO neurons showed an impaired long-term potentiation and
      hyperactivation of Ca(2+)/calmodulin-dependent protein kinase II. Therefore, JPs
      seem to have an essential role in neural excitability fundamental to plasticity
      and integrated functions.

PMID- 16809426
TI  - A functional variant of the dopamine D3 receptor is associated with risk and age
      at-onset of essential tremor.
AB  - Familial essential tremor (ET), the most common inherited movement disorder, is
      generally transmitted as an autosomal dominant trait. A genome-wide scan for ET
      revealed one major locus on chromosome 3q13. Here, we report that the Ser9Gly
      variant in the dopamine D(3) receptor gene (DRD3), localized on 3q13.3, is
      associated and cosegregates with familial ET in 23 out of 30 French families.
      Sequencing revealed no other nonsynonymous variants in the DRD3-coding sequence
      and in the first 871 bp of the 5' flanking region. Moreover, Gly-9 homozygous
      patients presented with more severe and/or earlier onset forms of the disease
      than heterozygotes. A replication study comparing 276 patients with ET and 184
      normal controls confirmed the association of the Gly-9 variant with risk and age
      at-onset of ET. In human embryonic kidney (HEK) 293-transfected cells, the Gly-9
      variant did not differ from the Ser-9 variant with respect to glycosylation and
      to anterograde and retrograde trafficking, but dopamine had an affinity that was
      four to five times higher. With the Gly-9 variant, the dopamine-mediated cAMP
      response was increased, and the mitogen-associated protein kinase (MAPK) signal
      was prolonged, as compared with the Ser-9 variant. The gain-of-function produced
      by the Gly-9 variant may explain why drugs active against tremor in Parkinson's
      disease (PD) are usually not effective in the treatment of ET and suggests that
      DRD3 partial agonists or antagonists should be considered as novel therapeutic
      options for patients with ET.

PMID- 16809428
TI  - Re: "Applying recursive partitioning to a prospective study of factors associated
      with adherence to mammography screening guidelines".

PMID- 16809427
TI  - Differentiation of embryonic stem cells conditionally expressing neurogenin 3.
AB  - Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the
      development of pancreatic islets. To better characterize the molecular events
      regulated by Ngn3 during development, we have determined the expression profiles
      of murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An
      mESC line was created in order to induce Ngn3 by adding doxycycline to the
      culture medium. Genome-wide microarray analysis was performed to identify genes
      regulated by Ngn3 in a variety of contexts, including undifferentiated ESCs and
      differentiating embryoid bodies (EBs). Genes regulated by Ngn3 in a context
      independent manner were identified and analyzed using systematic gene ontology
      tools. This analysis revealed Notch signaling as the most significantly regulated
      signaling pathway (p = .009). This result is consistent with the hypothesis that
      Ngn3 expression makes the cell competent for Notch signaling to be activated and,
      conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to
      express Ngn3 were significantly more sensitive to gamma-secretase inhibitor
      mediated Notch signaling inhibition (p < .0001) when compared with uninduced EBs.
      Moreover, we find that Ngn3 induction in differentiating ESCs results in
      significant increases in insulin, glucagon, and somatostatin expression.

PMID- 16809429
TI  - Disease mapping and spatial regression with count data.
AB  - In this paper, we provide critical reviews of methods suggested for the analysis
      of aggregate count data in the context of disease mapping and spatial regression.
      We introduce a new method for picking prior distributions, and propose a number
      of refinements of previously used models. We also consider ecological bias,
      mutual standardization, and choice of both spatial model and prior specification.
      We analyze male lip cancer incidence data collected in Scotland over the period
      1975-1980, and outline a number of problems with previous analyses of these data.
      In disease mapping studies, hierarchical models can provide robust estimation of
      area-level risk parameters, though care is required in the choice of covariate
      model, and it is important to assess the sensitivity of estimates to the spatial
      model chosen, and to the prior specifications on the variance parameters. Spatial
      ecological regression is a far more hazardous enterprise for two reasons. First,
      there is always the possibility of ecological bias, and this can only be
      alleviated by the inclusion of individual-level data. For the Scottish data, we
      show that the previously used mean model has limited interpretation from an
      individual perspective. Second, when residual spatial dependence is modeled, and
      if the exposure has spatial structure, then estimates of exposure association
      parameters will change when compared with those obtained from the independence
      across space model, and the data alone cannot choose the form and extent of
      spatial correlation that is appropriate.

PMID- 16809430
TI  - On the equivalence of case-crossover and time series methods in environmental
      epidemiology.
AB  - The case-crossover design was introduced in epidemiology 15 years ago as a method
      for studying the effects of a risk factor on a health event using only cases. The
      idea is to compare a case's exposure immediately prior to or during the case
      defining event with that same person's exposure at otherwise similar "reference"
      times. An alternative approach to the analysis of daily exposure and case-only
      data is time series analysis. Here, log-linear regression models express the
      expected total number of events on each day as a function of the exposure level
      and potential confounding variables. In time series analyses of air pollution,
      smooth functions of time and weather are the main confounders. Time series and
      case-crossover methods are often viewed as competing methods. In this paper, we
      show that case-crossover using conditional logistic regression is a special case
      of time series analysis when there is a common exposure such as in air pollution
      studies. This equivalence provides computational convenience for case-crossover
      analyses and a better understanding of time series models. Time series log-linear
      regression accounts for overdispersion of the Poisson variance, while case
      crossover analyses typically do not. This equivalence also permits model checking
      for case-crossover data using standard log-linear model diagnostics.

PMID- 16809431
TI  - Parental resources, parental stress, and socioemotional development of deaf and
      hard of hearing children.
AB  - In recent years, empowerment and resource orientation have become vital
      guidelines for many of the sciences. For the field of deaf education, it is also
      highly important to look carefully at these guidelines if we are to acquire a
      better understanding as regards both the situation of the parents involved and
      the development of the deaf and hard of hearing children themselves. A resource
      oriented approach to deaf education has therefore proved especially helpful. If
      both the theoretical and practical aspects of educating deaf and hard of hearing
      children are to benefit, research on parental experience with deafness and
      research on the socioemotional development of the children must always be
      combined and studied in the context of resource availability. In a study of 213
      mothers and 213 fathers of deaf and hard of hearing children, we used an array of
      different questionnaires (PSI, SDQ, SOC, F-SozU, etc.) to examine the correlation
      between parental resources, sociodemographic variables, parental stress
      experience, and child socioemotional problems by way of a path analysis model.
      The results show that high parental stress is associated with frequent
      socioemotional problems in the children, thus emphasizing the importance of a
      resource-oriented consulting and support strategy in early intervention, because
      parental access to personal and social resources is associated with significantly
      lower stress experience. Child development seems to profit enormously from a
      resource-oriented support concept. In addition, the results confirm two earlier
      findings: parents with additionally handicapped children are especially stressed
      and the child's communicative competence makes for a more sound prediction than
      its linguistic medium (spoken language or sign). The path models for mothers and
      fathers agree in all essential factors. The results are discussed with a view to
      their meaning for pedagogical practice, and recommendations for further research
      are given (longitudinal data, more representative samples, cochlear implant).

PMID- 16809433
TI  - A role for skeletal muscle stearoyl-CoA desaturase 1 in control of thermogenesis.
AB  - An enhanced metabolic efficiency for accelerating the recovery of fat mass (or
      catch-up fat) is a characteristic feature of body weight regulation after weight
      loss or growth retardation and is the outcome of an "adipose-specific"
      suppression of thermogenesis, i.e., a feedback control system in which signals
      from the depleted adipose tissue fat stores exert a suppressive effect on
      thermogenesis. Using a previously described rat model of semistarvation-refeeding
      in which catch-up fat results from suppressed thermogenesis per se, we report
      here that the gene expression of stearoyl-coenzyme A desaturase 1 (SCD1) is
      elevated in skeletal muscle after 2 wk of semistarvation and remains elevated in
      parallel to the phase of suppressed thermogenesis favoring catch-up fat during
      refeeding. These elevations in the SCD1 transcript are skeletal muscle specific
      and are associated with elevations in microsomal Delta9 desaturase enzyme
      activity, in the Delta9 desaturation index, and in the relative content of SCD1
      derived monounsaturates in several lipid fractions extracted from skeletal
      muscle. An elevated skeletal muscle SCD1, by desaturating the products of de novo
      lipogenesis and diverting them away from mitochondrial oxidation, would inhibit
      substrate cycling between de novo lipogenesis and lipid oxidation, thereby
      leading to a state of suppressed thermogenesis that regulates the body's fat
      stores.

PMID- 16809432
TI  - Developmental exposure to the pesticide dieldrin alters the dopamine system and
      increases neurotoxicity in an animal model of Parkinson's disease.
AB  - Exposure to pesticides has been suggested to increase the risk of Parkinson's
      disease (PD), but the mechanisms responsible for this association are not clear.
      Here, we report that perinatal exposure of mice during gestation and lactation to
      low levels of dieldrin (0.3, 1, or 3 mg/kg every 3 days) alters dopaminergic
      neurochemistry in their offspring and exacerbates MPTP toxicity. At 12 wk of age,
      protein and mRNA levels of the dopamine transporter (DAT) and vesicular monoamine
      transporter 2 (VMAT2) were increased by perinatal dieldrin exposure in a dose
      related manner. We then administered MPTP (2 x 10 mg/kg s.c) at 12 wk of age and
      observed a greater reduction of striatal dopamine in dieldrin-exposed offspring,
      which was associated with a greater DAT:VMAT2 ratio. Additionally, dieldrin
      exposure during development potentiated the increase in GFAP and alpha-synuclein
      levels induced by MPTP, indicating increased neurotoxicity. In all cases there
      were greater effects observed in the male offspring than the female, similar to
      that observed in human cases of PD. These data suggest that developmental
      exposure to dieldrin leads to persistent alterations of the developing
      dopaminergic system and that these alterations induce a "silent" state of
      dopamine dysfunction, thereby rendering dopamine neurons more vulnerable later in
      life.

PMID- 16809434
TI  - Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal
      damage and enhances irinotecan/temozolomide efficacy against colon carcinoma.
AB  - Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the antitumor activity of
      the topoisomerase I inhibitor irinotecan (CPT-11), which is used to treat
      advanced colorectal carcinoma. Since PARP inhibitors sensitize tumor cells also
      to the methylating agent temozolomide (TMZ) and clinical trials are evaluating
      CPT-11 in combination with TMZ, we tested whether the PARP inhibitor GPI 15427
      (10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one)
      increases the efficacy of CPT-11 + TMZ against colon cancer. Moreover, due to the
      ability of PARP inhibitors to avoid cell death consequent to PARP-1
      overactivation, we evaluated whether oral administration of GPI 15427 provides
      protection from the dose-limiting intestinal toxicity of CPT-11. The results of
      colony formation assay indicated that GPI 15427 increased the antiproliferative
      effects (combination index <1) of TMZ + SN-38 (the active metabolite of CPT-11)
      against colon cancer cells. Accordingly, GPI 15427 (40 mg/kg/dayx5 days per os)
      in combination with TMZ (10 mg/kg/dayx5 days) + CPT-11 (4 mg/kg/dayx5 days)
      significantly reduced the growth of tumor xenografts. Oral administration of GPI
      15427 (40 mg/kg/q2x3 days) prevented intestinal injury and diarrhea induced by
      CPT-11 (30 mg/kg/day x 3 days) reducing inflammation and PARP-1 overactivation,
      as evidenced by immunohistochemical staining of intestinal tissue with
      antipoly(ADP-ribose) antibody (Ab). In conclusion, the PARP inhibitor represents
      a novel strategy to enhance the antitumor efficacy and reduce toxicity of
      chemotherapy in colon cancer.

PMID- 16809435
TI  - Protein glutathiolation by nitric oxide: an intracellular mechanism regulating
      redox protein modification.
AB  - This study was designed to examine whether NO regulates protein glutathiolation.
      Exposure to NO donors increased protein glutathiolation in COS-7 or rat aortic
      smooth muscle cells as detected by anti-protein glutathione (GSH) antibodies.
      This process was reversible and saturable. Stimulation with acetylcholine (ACh)
      increased protein glutathiolation in isolated rat aortic rings. This was
      prevented by inhibiting endothelial NO synthase (eNOS). In ACh-treated rings,
      proteins showing positive immunoreactivity with the anti-PSSG antibody (Ab) were
      identified by matrix assisted laser desorption-time-of-flight mass spectrometry
      to be actin, vimentin, and heat shock protein 70. Purified actin was more readily
      glutathiolated by S-nitrosoglutathione than by oxidized GSH as determined by
      electrospray-ionization mass spectrometry, and nitrosylated actin was
      glutathiolated by reduced GSH. Relative to wild-type (WT) mice, increased protein
      glutathiolation was observed in hearts of mice with cardiac-specific expression
      of inducible NO synthase (iNOS). Proteins immunoprecipitated from transgenic
      hearts revealed GSH-adducted peptides corresponding to adenine nucleotide
      translocator and the alpha-subunit of F1F0ATPase. These data suggest that
      exogenous NO or NO generated by eNOS or iNOS regulates protein adduction with
      GSH. This could be due to a direct reaction of proteins with S-nitrosoglutathione
      or denitrosylation of S-nitrosylated proteins by reduced GSH. Glutathiolation of
      cytoskeletal and mitochondrial proteins may be a significant feature of NO
      bioreactivity.

PMID- 16809437
TI  - Testicular gene expression profiling following prepubertal rat mono-(2
      ethylhexyl) phthalate exposure suggests a common initial genetic response at
      fetal and prepubertal ages.
AB  - Phthalate chemical plasticizers can damage the fetal and postnatal mammalian
      testis, but several aspects of the injury mechanism remain unknown. Using a
      genome-wide microarray, the profile of testicular gene expression changes was
      examined following exposure of postnatal day 28 rats to a single, high dose (1000
      mg/kg) of mono-(2-ethylhexyl) phthalate (MEHP). By microarray analysis,
      approximately 1675 nonredundant genes exhibited significant expression changes;
      the vast majority were observed at 12 h. Among the 36 genes significantly altered
      up to the 3-h time point, prominent functional categories were secreted,
      transcription, and signaling factors. Using quantitative PCR (qPCR), the dose
      response of 24 genes was determined after a single MEHP exposure of 10, 100, or
      1000 mg/kg. Increasing 114-fold by 12 h at 1000 mg/kg, Thbs1 (thrombospondin 1)
      showed the highest level of gene induction. The vast majority of genes analyzed
      by qPCR exhibited significant expression alterations at the lowest dose level.
      Interestingly, a unique, dose-dependent expression pattern was observed for the
      transcription factor Nr0b1, steroidogenic genes (Cyp17a1 and StAR), and a
      cholesterol metabolism gene (Dhcr7). For these genes, the direction of expression
      change at 10 or 100 mg/kg was opposite that observed at 1000 mg/kg. Gene
      profiling data at 1000 mg/kg MEHP were phenotypically anchored to increased germ
      cell apoptosis (6 and 12 h) and an interstitial neutrophil infiltrate (12 h). At
      10 or 100 mg/kg MEHP, no testicular morphological changes were detected, but a
      significant increase in germ cell apoptosis was seen at 6 h. Finally, comparison
      of the prepubertal MEHP microarray data to similar data from fetal dibutyl
      phthalate (DBP) exposure showed conservation in both the identities of testicular
      genes altered and the direction of expression changes. For example, 60% of the
      genes altered within 3 h of prepubertal MEHP exposure also were changed following
      acute fetal DBP exposure, and the direction of expression change was highly
      preserved. These data demonstrate that similar genetic targets are altered
      following fetal and prepubertal phthalate exposure, suggesting that the initial
      mechanism of fetal and prepubertal phthalate-induced testicular injury is shared.

PMID- 16809436
TI  - Macrophage migration inhibitory factor in the PVN attenuates the central pressor
      and dipsogenic actions of angiotensin II.
AB  - Macrophage migration inhibitory factor (MIF) acts intracellularly to counteract
      the angiotensin (ANG) II type 1 receptor (AT1-R)-mediated chronotropic effect of
      ANG II in hypothalamic neurons, an effect mediated by the thiol-protein
      oxidoreductase (TPOR) activity of the MIF molecule. Here we determined the in
      vivo actions of MIF in regulating the physiological actions of ANG II that are
      mediated via the paraventricular nucleus (PVN), an area that serves as a relay
      point in the central nervous system (CNS)-mediated effects of ANG II on
      cardiovascular functions and water intake. Intracerebroventricular (icv)
      injection of ANG II into normotensive rats selectively increased MIF protein
      levels in the PVN and produced significant pressor and drinking responses that
      were inhibited by PVN administration of the AT1-R antagonist losartan.
      Overexpression of MIF in PVN neurons via Ad-Syn-MIF gene transfer attenuated the
      pressor and drinking responses produced by icv-injected ANG II. Consistently,
      intracellular application of MIF or MIF-(50-65) (which harbors the TPOR activity
      of MIF) into PVN sympathetic regulatory neurons, blunted the electrophysiological
      actions of ANG II at these cells. These observations establish for the first time
      that MIF within the PVN, acting via TPOR, is an intracellular regulator of the
      central cardiovascular and dipsogenic effects of ANG II.

PMID- 16809438
TI  - Use of lectins for probing differentiated human embryonic stem cells for
      carbohydrates.
AB  - The carbohydrates present on the surface of differentiated human embryonic stem
      cells (hESCs) are not yet well established. Here, we have employed a panel of
      lectins and several anti-carbohydrate antibodies to determine the carbohydrates
      that are present at day 12 of hESC differentiation as embryoid bodies (EBs). On
      the basis of staining with fluorescein-labeled lectins, we have determined the
      presence of both terminal and internally linked alpha-d-mannopyranosyl groups,
      poly-N-acetyllactosaminyl chains, both alpha2,3- and alpha2,6-linked N
      acetylneuraminic acid (Neu5Ac), alpha1,6-linked l-fucosyl, and beta-D-galactosyl
      groups, and more specifically, the T, Tn, and sialyl-Tn antigens. However, no
      alpha1,2-linked l-fucosyl, terminal nonreducing alpha-D-galactosyl, N-acetyl-beta
      D-glucosaminyl, nor N-acetyl-alpha-D-galactosaminyl groups were found by this
      approach. We also established the presence of Neu5Acalpha2,3/2,6-Galbeta1,4
      GlcNAc-terminated chains on the surfaces of 12-day-old EBs, as indicated by the
      great enhancement of staining by Erythrina cristagalli agglutinin (ECA) after
      treatment with neuraminidase. In each case, inhibition of binding by a haptenic
      sugar or treatment with neuraminidase was used to eliminate the possibility of
      nonspecific binding of the lectins. A comparison with undifferentiated cell
      staining revealed an increase in alpha2,3-linked Neu5Ac as well as a change to
      exclusively alpha1,6-linked l-fucose upon differentiation.

PMID- 16809439
TI  - Targeting fatty acid synthase in breast and endometrial cancer: An alternative to
      selective estrogen receptor modulators?
AB  - There is an urgent need to identify and develop a new generation of therapeutic
      agents and systemic therapies targeting the estradiol (E2)/estrogen receptor (ER)
      signaling in breast cancer. In this regard, new information on the mechanisms of
      E2/ER function and/or cross talk with other prosurvival cascades should provide
      the basis for the development of other ideal anti-E2 therapies with the intent to
      enhance clinical efficacy, reduce side effects or both. Our very recent
      assessment of the mechanisms by which cancer-associated increased lipogenesis and
      its inhibition alters the E2/ER signaling discovered that fatty acid synthase
      (FASN), the enzyme catalyzing the terminal steps in the de novo biosynthesis of
      long-chain fatty acids, differentially modulates the state of sensitivity of
      breast and endometrial cancer cells to E2-stimulated ER transcriptional
      activation and E2-dependent cell growth and survival: 1) pharmacological
      inhibition of FASN activity induced a dramatic augmentation of E2-stimulated ER
      driven gene transcription, whereas interference (RNAi)-mediated silencing of FAS
      gene expression drastically lowered E2 requirements for optimal activation of ER
      transcriptional activation in breast cancer cells; conversely, pharmacological
      and RNAi-induced inhibition of FASN worked as an antagonist of E2- and tamoxifen
      dependent ER transcriptional activity in endometrial adenocarcinoma cells; 2)
      pharmacological and RNAi-induced inhibition of FASN synergistically enhanced E2
      mediated down-regulation of ER protein and mRNA expression in breast cancer
      cells, whereas specific FASN blockade resulted in a marked down-regulation of E2
      stimulated ER expression in endometrial cancer cells; and 3) FASN inhibition
      decreased cell proliferation and cell viability by promoting apoptosis in hormone
      dependent breast and endometrial cancer cells. In this review we propose that,
      through a complex mechanism involving the regulation of MAPK/ER cross talk as
      well as critical E2-related proteins including the Her-2/neu (erbB-2) oncogene
      and the cyclin-dependent kinase inhibitors p21(WAF1/CIP1) and p27(Kip1), a
      previously unrevealed connection exists between FASN and the genomic and
      nongenomic ER activities in breast and endometrial cancer cells. From a clinical
      perspective, we suggest that if chemically stable FASN inhibitors or cell
      selective systems able to deliver RNAi targeting FASN gene demonstrate systemic
      anticancer effects of FASN inhibition in vivo, additional preclinical studies to
      characterize their anti-breast cancer actions should be of great interest as the
      specific blockade of FASN activity may also provide a protective means against
      endometrial carcinoma associated with tamoxifen-based breast cancer therapy.

PMID- 16809440
TI  - S14: insights from knockout mice.
AB  - Spot 14 (S14) is a protein whose mRNA is rapidly up-regulated by lipogenic
      stimuli including thyroid hormone and a high-carbohydrate diet. Previous
      investigation into the role of S14 suggested that it is involved in de novo
      lipogenesis. Knockout of the gene in mice has given further support to this
      hypothesis. The lack of S14 in different tissues resulted in varying phenotypic
      effects. In the lactating mammary gland, levels of lipogenesis, specifically the
      production of medium chain fatty acids, were decreased, whereas hepatic
      lipogenesis was not decreased. In fact, hepatic lipogenesis was increased, and
      the increase may be due to compensation by a paralog of S14 called S14-R. S14-R
      is expressed in the liver but not the mammary gland. Importantly, S14 knockout
      mice did not have reduced levels of lipogenic enzymes, implying that it does not
      affect the transcriptional rate of those enzymes. Instead, S14 may act in the
      cytoplasm to affect lipogenesis.

PMID- 16809441
TI  - Spot 14: A marker of aggressive breast cancer and a potential therapeutic target.
AB  - Spot 14 (S14) is a nuclear protein that communicates the status of dietary fuels
      and fuel-related hormones to genes required for long-chain fatty acid synthesis.
      In mammary gland, S14 is important for both epithelial proliferation and milk fat
      production. The S14 gene is amplified in some breast cancers and is strongly
      expressed in most. High expression of S14 in primary invasive breast cancer is
      conspicuously predictive of recurrence. S14 mediates the induction of lipogenesis
      by progestin in breast cancer cells and accelerates their growth. Conversely, S14
      knockdown impairs de novo lipid synthesis and causes apoptosis. We found that
      breast cancer cells do not express lipoprotein lipase (LPL) and hypothesize that
      they do not have access to circulating lipids unless the local environment
      supplies it. This may explain why primary breast cancers with low S14 do not
      survive transit from the LPL-rich mammary fat pad to areas devoid of LPL, such as
      lymph nodes, and thus do not appear as distant metastases. Thus, S14 is a marker
      for aggressive breast cancer and a potential target as well. Future effort will
      center on validation of S14 as a therapeutic target and producing antagonists of
      its action.

PMID- 16809442
TI  - Impact of estrogen receptor beta on gene networks regulated by estrogen receptor
      alpha in breast cancer cells.
AB  - Two subtypes of the estrogen receptor (ER), ERalpha and ERbeta, mediate the
      actions of estrogens, and although 70% of human breast cancers express ERbeta
      along with ERalpha, little is known about the possible comodulatory effects of
      these two ERs. To investigate this, we have used adenoviral gene delivery to
      produce human breast cancer (MCF-7) cells expressing different levels of ERbeta,
      along with their endogenous ERalpha, and have examined the effects of ERbeta and
      receptor occupancy, using ER subtype selective ligands, on genome-wide gene
      expression by microarray and pathway network analysis. ERbeta had diverse effects
      on gene expression, enhancing or counteracting ERalpha regulation for distinct
      subsets of estrogen target genes. Strikingly, ERbeta in the absence of estradiol
      (E2), elicited the stimulation or suppression of many genes that were normally
      only regulated by ERalpha with E2. In addition, ERbeta plus E2 elicited the
      expression of a unique group of genes that were not regulated by ERalpha plus E2
      alone. The expression of genes in many functional categories were modulated by
      ERbeta, with the greatest numbers associated with transcription factors and
      signal transduction pathways. Regulation of multiple components in the TGFbeta
      and semaphorin pathways, and of genes controlling cell cycle progression and
      apoptosis, may contribute to the suppression of cell proliferation observed with
      ERbeta. Our observations suggest that the relative levels of ERbeta and ERalpha
      in breast cancers are likely to impact cell proliferation and the activities of
      diverse signaling pathways and their response to ER ligands and endocrine
      therapies.

PMID- 16809443
TI  - Urocortin 3 modulates the neuroendocrine stress response and is regulated in rat
      amygdala and hypothalamus by stress and glucocorticoids.
AB  - The endogenous corticotropin-releasing factor (CRF) type 2 receptor (CRFR2)
      selective ligand urocortin 3 is expressed in discrete subcortical brain regions
      with fibers distributed mainly to hypothalamic and limbic structures. Close
      anatomical association between major urocortin 3 terminal fields and CRFR2 in
      hypothalamus, lateral septum, and medial amygdala (MEA) suggest it is well placed
      to modulate behavioral and hormonal responses to stress. Urocortin 3 was
      administered intracerebroventricularly to male rats under basal conditions or
      before a restraint stress, and circulating ACTH, corticosterone, glucose, and
      insulin were measured. Urocortin 3 activated the hypothalamic-pituitary-adrenal
      axis under basal conditions and augmented ACTH responses to restraint stress.
      Elevated blood glucose with lowered insulin to glucose ratios in both groups
      suggested increased sympathetic activity. Circulating catecholamines were also
      increased by urocortin 3, providing additional evidence for
      sympathoadrenomedullary stimulation. Intracerebroventricular urocortin 3
      increased vasopressin mRNA expression in the parvocellular division of the
      hypothalamic paraventricular nucleus, whereas CRF expression was unchanged,
      providing a possible mechanism by which urocortin 3 mediates its actions.
      Urocortin 3 mRNA expression was examined after exposure to stress-related
      paradigms. Restraint increased levels in MEA with a trend to increased expression
      in the rostral perifornical hypothalamic area, whereas hemorrhage and food
      deprivation decreased expression in MEA. Adrenalectomy markedly increased
      expression in the rostral perifornical hypothalamic area, and high-level
      corticosterone replacement restored this to control levels. The evidence that
      urocortin 3 has the potential to influence hormonal components of the stress
      response and the changes in its expression levels after stressors is consistent
      with a potential function for the endogenous peptide in modulating stress
      responses.

PMID- 16809444
TI  - Pituitary tumor transforming gene overexpression facilitates pituitary tumor
      development.
AB  - Intrinsic and extrinsic stimuli result in profound pituitary growth changes
      ranging from hypoplasia to hyperplasia. Pituitary tumor transforming gene (PTTG)
      abundance correlates with pituitary trophic status. Mice with Pttg inactivation
      exhibit pituitary hypoplasia, whereas targeted pituitary PTTG overexpression
      driven by alpha-subunit glycoprotein (alphaGSU) promoter results in focal
      pituitary hyperplasia. To test the impact of pituitary hyperplasia on tumor
      development, we crossbred alphaGSU.PTTG with Rb+/- mice, which develop pituitary
      tumors with high penetrance. Pituitary glands of resulting bitransgenic
      alphaGSU.PTTGxRb+/- mice were compared with monotransgenic alphaGSU.PTTG, Rb+/-,
      and wild-type mice. Confocal microscopy showed that PTTG-overexpressing cells
      have enlarged nuclei and marked redistribution of chromatin, and electron
      microscopy of alphaGSU.PTTG pituitaries showed enlarged gonadotrophs with
      prominent Golgi complexes and numerous secretory granules. These morphological
      findings were even more remarkable in alphaGSU.PTTGxRb+/- pituitaries. Mice from
      all four genotypes were sequentially imaged by magnetic resonance imaging to
      evaluate pituitary volume, and glands from alphaGSU.PTTGxRb+/- mice were the
      largest as early as 2 months of age (P = 0.0003). Cumulative incidence of
      pituitary tumors visualized by magnetic resonance imaging did not differ between
      Rb+/- and alphaGSU.PTTGxRb+/- mice. However, anterior lobe tumors determined
      after necropsy were 3.5 times more frequent in alphaGSU.PTTGxRb+/- than in Rb+/-
      mice (P = 0.0036), whereas the frequency of intermediate lobe tumors was similar.
      In summary, alphaGSU.PTTGxRb+/- pituitary glands exhibit enhanced cellular
      activity, increased volume, and higher prevalence of anterior pituitary tumors,
      indicating that changes in pituitary PTTG content directly relate to both
      pituitary trophic status and tumorigenic potential.

PMID- 16809445
TI  - The prolactin-deficient mouse has an unaltered metabolic phenotype.
AB  - Prolactin (PRL), best recognized for its lactogenic activity, is also involved in
      the regulation of metabolic homeostasis in both mammalian and nonmammalian
      species. Although several mouse models have been used to study the metabolic
      functions of PRL, a clear-cut consensus has not emerged given the limited and
      often conflicting data. To clarify the role of PRL in metabolic homeostasis in
      males and nonlactating females, we used the PRL-deficient mouse. Our objectives
      were to compare: 1) weight gain, 2) body composition, 3) serum lipid profile, 4)
      circulating leptin and adiponectin levels, and 5) glucose tolerance in PRL
      knockout, heterozygous, and wild-type mice maintained on standard chow, high-fat,
      or low-fat diets. In addition, we compared the lipolytic actions of PRL using
      adipose tissue explants from mice, rats, and humans. We are reporting that PRL
      deficiency does not affect the rate of weight gain, body composition, serum
      lipids, or adiponectin levels in either sex on any diet. Glucose tolerance was
      slightly impaired in very young PRL knockout male pups but not in adults or in
      females at any age. Leptin was elevated in male, but not female, PRL knockout
      mice maintained on a low-fat diet. PRL did not affect lipolysis in adipose tissue
      explants from mice but significantly inhibited glycerol release from both rat and
      human adipose explants in a dose-dependent manner. We conclude that PRL
      deficiency has negligible gross metabolic effects in mice.

PMID- 16809446
TI  - Insulin-like growth factor binding protein (IGFBP-1) involvement in intrauterine
      growth retardation: study on IGFBP-1 overexpressing transgenic mice.
AB  - In humans, intrauterine growth retardation is correlated to high levels of serum
      IGF binding protein-1 (IGFBP-1). This present study analyzes in vivo the impact
      of circulating IGFBP-1 on body growth associated to bone mineralization and
      carbohydrate resources. Transgenic mice used in this work overexpressed human
      IGFBP-1 in liver from embryonic day (E)14.5, concomitantly to the appearance of
      ossification centers, through to adulthood. Growth retardation was observed as
      early as E17.5 in homozygous (HM) mice being 20% smaller at birth (postnatal d
      1). Anatomical analysis of the skeletons by alizarin red and alcian blue staining
      showed that the mice exhibited pleiotropic defects of several skeletal units.
      Some bones were small and dysmorphic. Our results showed reduced mineralization
      in the posterior area of the skull (delayed suture closure), as well as in the
      appendicular and axial skeleton. Heterozygous crossings showed a loss of HM
      animals. Moreover, IGFBP-1 overexpression contributed to decreased fetal hepatic
      glycogen and neonate blood glucose levels which constitute the main reservoir of
      carbohydrate resources for neonates. Thus, this reduced carbohydrate pool
      contributed to perinatal mortality. Maternal IGFBP-1 expression was also clearly
      associated with neonate growth retardation (newborn weights from HM mothers were
      20% smaller than newborns from NT mothers) and reduced fetal carbohydrate
      resources. In conclusion, antenatal growth retardation and delayed mineralization
      in transgenic mice are related to overexpressed fetal and maternal circulating
      human IGFBP-1. Similar perturbations could be observed in human intrauterine
      growth retardation suggesting the IGF/IGFBP system is involved in fetal growth,
      biomineralization, and energetic status in humans.

PMID- 16809447
TI  - Androgen-dependent mechanisms of Wolffian duct development and their perturbation
      by flutamide.
AB  - Androgens play a vital role in Wolffian duct (WD) development, but the mechanisms
      that underlie this are unknown. The present study used in utero exposure of
      pregnant rats to the androgen receptor antagonist flutamide (50 or 100 mg/kg) to
      explore possible mechanisms. Pregnant rats were treated from embryonic d 15.5
      (E15.5), and WDs were isolated from fetuses from E17.5-E21.5 and from adults. WD
      morphology was evaluated, and total length of the duct lumen was determined in
      fetal samples. Fetal WDs were immunostained for androgen receptor and stromal
      (inner and outer) and/or epithelial-cell-specific markers and analyzed for cell
      proliferation and apoptosis. In adulthood, most flutamide-exposed males lacked
      proximal WD-derived tissues, whereas at E18.5-E19.5, a time when the WD has
      completely regressed in females, a complete normal WD was present in all
      flutamide-exposed animals. This suggests that flutamide, at doses of 50 or 100
      mg/kg, interferes with WD differentiation, not stabilization. Consistent with
      this, WD elongation/coiling increased in controls by 204% between E19.5 and E21.5
      but increased less significantly (103%) in flutamide-exposed animals. This was
      associated with reduced cell proliferation, but there was no increase in
      apoptosis or change in expression of androgen receptor mRNA or protein. Flutamide
      treatment impaired differentiation of inner stromal cells, shown by decreased
      expression of smooth muscle actin, before effects were noted in the epithelium,
      consistent with androgens driving WD development via stromal-epithelial
      interactions. In conclusion, WD differentiation is far more susceptible to
      blockade of androgen action than is its initial stabilization, and these effects
      may be mediated by disruption of stromal-epithelial interactions.

PMID- 16809448
TI  - Expression and function of lysophosphatidic acid LPA1 receptor in prostate cancer
      cells.
AB  - The bioactive phospholipid lysophosphatidic acid (LPA) promotes cell
      proliferation, survival, and migration by acting on cognate G protein-coupled
      receptors named LPA(1), LPA(2), and LPA(3). We profiled gene expression of LPA
      receptors in androgen-dependent and androgen-insensitive prostate cancer cells
      and found that LPA(1) gene is differentially expressed in androgen-insensitive
      and LPA-responsive but not androgen-dependent and LPA-resistant cells. In human
      prostate specimens, expression of LPA(1) gene was significantly higher in the
      cancer compared with the benign tissues. The androgen-dependent LNCaP cells do
      not express LPA(1) and do not proliferate in response to LPA stimulation,
      implying LPA(1) transduces cell growth signals. Accordingly, stable expression of
      LPA(1) in LNCaP cells rendered them responsive to LPA-induced cell proliferation
      and decreased their doubling time in serum. Implantation of LNCaP-LPA(1) cells
      resulted in increased rate of tumor growth in animals compared with those tumors
      that developed from the wild-type cells. Growth of LNCaP cells depends on
      androgen receptor activation, and we show that LPA(1) transduces Galphai
      dependent signals to promote nuclear localization of androgen receptor and cell
      proliferation. In addition, treatment with bicalutamide inhibited LPA-induced
      cell cycle progression and proliferation of LNCaP-LPA(1) cells. These results
      suggest the possible utility of LPA(1) as a drug target to interfere with
      progression of prostate cancer.

PMID- 16809449
TI  - Corticosterone can act at the posterior paraventricular thalamus to inhibit
      hypothalamic-pituitary-adrenal activity in animals that habituate to repeated
      stress.
AB  - Glucocorticoids released by stress bind to glucocorticoid (GR) and/or
      mineralocorticoid receptors (MR) to exert negative feedback of subsequent
      hypothalamic-pituitary-adrenal (HPA) responses to stress. Feedback inhibition is
      implicated in habituation of HPA activity to repeated exposure to the same
      (homotypic) stressor. We hypothesized that the posterior paraventricular thalamus
      (pPVTh) is a site where corticosterone acts to exert negative feedback during
      repeated stress and that is important for habituation. As previously reported,
      the pPVTh inhibits HPA responses to homotypic and heterotypic stressors in
      repeatedly, but not acutely, stressed rats. We conducted a series of experiments
      involving intra-pPVTh administration of MR and/or GR agonists or antagonists
      during different time frames over 8 d of restraint. MR exist in the pPVTh, as do
      GR as shown by our immunocytochemical results. Acute intra-pPVTh injection of MR
      and/or GR antagonist before the eighth restraint did not alter expression of
      habituation. Because habituation may develop before d 8, we manipulated GR and MR
      in the pPVTh throughout 8 d of stress using intra-pPVTh corticosterone implants,
      which enhanced habituation on d 8 without affecting acute stress responses.
      Conversely, daily intra-pPVTh injections of GR and MR antagonists on d 1-7 of
      restraint prevented habituation on d 8. These data suggest that corticosterone
      released during repeated stress can act at GR and MR in the pPVTh to inhibit HPA
      responses to homotypic stress. We also found that some GR-containing cells in the
      pPVTh project to the medial prefrontal cortex and basolateral amygdala,
      suggesting that pPVTh-induced inhibition of HPA activity is potentially mediated
      by its projections to these select limbic structures.

PMID- 16809450
TI  - Role of tyrosine kinase receptors in angiotensin II AT2 receptor signaling:
      involvement in neurite outgrowth and in p42/p44mapk activation in NG108-15 cells.
AB  - NG108-15 cells, which have a rounding-up morphology when cultured in serum
      supplemented medium, extend neurites when stimulated for 3 d with angiotensin II
      (Ang II). The aim of the present study was to investigate whether growth factor
      receptors are necessary for mediating the effects of Ang II. A 3-d treatment with
      AG879, an inhibitor of nerve growth factor receptor TrkA, strongly affected
      neurite outgrowth and phosphorylation of p42/p44(mapk) induced by Ang II.
      PD168393, an inhibitor of epidermal growth factor (EGF) receptor slightly
      decreased Ang II-induced neurite outgrowth, whereas AG213, an inhibitor of both
      platelet-derived growth factor receptor and EGF receptor, stimulated neurite
      outgrowth and p42/p44(mapk) phosphorylation on its own, without affecting further
      stimulation with Ang II. Moreover, Ang II induced the phosphorylation of TrkA
      (maximum at 5 min of incubation in the presence of serum or at 20 min in cells
      depleted in serum for 2 h) and a rapid increase in Rap1 activity, both effects
      abolished in cells preincubated with 10 microm AG879. In summary, the present
      results demonstrate that AT(2) receptor-induced sustained activation of
      p42/p44(mapk) and corresponding neurite outgrowth are mediated by phosphorylation
      of the nerve growth factor TrkA receptor. However, the results also point out
      that the presence of other growth factors, such as EGF or PDFG, may interfere
      with the effect of Ang II. Altogether, the current findings clearly indicate that
      the effects of the AT(2) receptor on neurite outgrowth dynamics are modulated by
      the presence of growth factors in the culture medium.

PMID- 16809451
TI  - Small cuticular domes are strain receptors.

PMID- 16809452
TI  - Why are so many adhesive pads hairy?
AB  - Many arthropods and vertebrates possess tarsal adhesive pads densely covered with
      setae. The striking morphological convergence of ;hairy' pads in lizards, spiders
      and several insect orders demonstrates the advantage of this design for substrate
      adhesion. Early functional explanations of hairy adhesive organs focused on the
      performance on rough substrates, where flexible setae can make more intimate
      contact. Recent theoretical and experimental work shows that the hairy design can
      also help to achieve self-cleaning properties, controllable detachment and
      increased adhesion. Several arguments have been proposed to explain why adhesive
      forces are maximised. First, the ;Force scaling' hypothesis states that when
      adhesive forces scale linearly with the dimensions of the contact, adhesion is
      increased by dividing the contact zone into many microscopic subunits. Second,
      the ;Fracture mechanics' argument implies that adhesion is maximised when the
      size of adhesive contacts is smaller than the critical crack length. Third, the
      ;Work of adhesion' model suggests that adhesion increases due to the bending and
      stretching of setae and associated energy losses during detachment. Several
      morphological traits of hairy adhesive pads can be explained by the need to
      maximise the work of adhesion, while avoiding the sticking of setae to each other
      (self-matting). Firstly, if setae are oblique and convex toward the foot tip as
      typical of most hairy pads, arrays should achieve greater adhesion. Secondly, a
      branched seta morphology not only confers the advantage that setae can adapt to
      roughness at different length scales but also prevents self-matting and increases
      the work of adhesion. It is predicted from the ;Work of adhesion' model that
      adhesion of pads with unbranched setae cannot be increased by subdividing the
      contact zone into ever finer subcontacts, because this would increasingly cause
      self-matting. However, contact splitting can increase adhesion if setae are
      branched. The greater density of setae in large animals has been interpreted by
      ;Force scaling'. However, the existing data can be explained by the effect of
      seta branching and by a fundamental difference between ;wet' and ;dry' adhesive
      systems. As insects employ adhesive fluids, they can cope with small-scale
      surface roughness even with relatively blunt seta tips, whereas the dry systems
      of lizards and spiders require extremely fine endings.

PMID- 16809453
TI  - Metabolic substrate use and the turnover of endogenous energy reserves in broad
      tailed hummingbirds (Selasphorus platycercus).
AB  - We fed broad-tailed hummingbirds (Selasphorus platycercus) diets of contrasting
      carbon isotope composition and measured changes in the delta(13)C of expired
      breath through time. By measuring the delta(13)C in the breath of fed and fasted
      birds we were able to quantify the fraction of metabolism fueled by assimilated
      sugars and endogenous energy reserves. These measurements also allowed us to
      estimate the fractional turnover of carbon in the hummingbirds' energy reserves.
      When hummingbirds were feeding, they fueled their metabolism largely (
      approximately 90%) with assimilated sugars. The rate of carbon isotope
      incorporation into the energy reserves of hummingbirds was higher when birds were
      gaining as opposed to losing body mass. The average residence time of a carbon
      atom in the hummingbirds' energy reserves ranged from 1 to 2 days.

PMID- 16809454
TI  - Evidence for a respiratory component, similar to mammalian respiratory sinus
      arrhythmia, in the heart rate variability signal from the rattlesnake, Crotalus
      durissus terrificus.
AB  - Autonomic control of heart rate variability and the central location of vagal
      preganglionic neurones (VPN) were examined in the rattlesnake (Crotalus durissus
      terrificus), in order to determine whether respiratory sinus arrhythmia (RSA)
      occurred in a similar manner to that described for mammals. Resting ECG signals
      were recorded in undisturbed snakes using miniature datalogging devices, and the
      presence of oscillations in heart rate (fh) was assessed by power spectral
      analysis (PSA). This mathematical technique provides a graphical output that
      enables the estimation of cardiac autonomic control by measuring periodic changes
      in the heart beat interval. At fh above 19 min(-1) spectra were mainly
      characterised by low frequency components, reflecting mainly adrenergic tonus on
      the heart. By contrast, at fh below 19 min(-1) spectra typically contained high
      frequency components, demonstrated to be cholinergic in origin. Snakes with a fh
      >19 min(-1) may therefore have insufficient cholinergic tonus and/or too high an
      adrenergic tonus acting upon the heart for respiratory sinus arrhythmia (RSA) to
      develop. A parallel study monitored fh simultaneously with the intraperitoneal
      pressures associated with lung inflation. Snakes with a fh<19 min(-1) exhibited a
      high frequency (HF) peak in the power spectrum, which correlated with ventilation
      rate (fv). Adrenergic blockade by propranolol infusion increased the variability
      of the ventilation cycle, and the oscillatory component of the fh spectrum
      broadened accordingly. Infusion of atropine to effect cholinergic blockade
      abolished this HF component, confirming a role for vagal control of the heart in
      matching fh and fv in the rattlesnake. A neuroanatomical study of the brainstem
      revealed two locations for vagal preganglionic neurones (VPN). This is consistent
      with the suggestion that generation of ventilatory components in the heart rate
      variability (HRV) signal are dependent on spatially distinct loci for cardiac
      VPN. Therefore, this study has demonstrated the presence of RSA in the HRV signal
      and a dual location for VPN in the rattlesnake. We suggest there to be a causal
      relationship between these two observations.

PMID- 16809455
TI  - Tiger moth responses to a simulated bat attack: timing and duty cycle.
AB  - Many night-flying insects perform complex, aerobatic escape maneuvers when
      echolocating bats initiate attack. Tiger moths couple this kinematic defense with
      an acoustic reply to a bat's biosonar-guided assault. The jamming hypothesis for
      the function of these moth sounds assumes that tiger moth clicks presented at
      high densities, temporally locked to the terminal phase of the bat attack will
      produce the greatest jamming efficacy. Concomitantly, this hypothesis argues that
      moths warning bats of bad tasting chemicals sequestered in their tissues should
      call early to give the bat time to process the meaning of the warning signal and
      that moths calling at low duty cycles are more likely to employ such an
      aposematic strategy. We report here the first investigation of a tiger moth
      assemblage's response to playback of a bat echolocation attack sequence. This
      assemblage of arctiid moths first answered the echolocation attack sequence 960+/
      547 ms (mean +/- s.d.) from the end of the bat attack. The assemblage reached a
      half-maximum response shortly after the first response, at 763+/-479 ms from the
      end of the terminal buzz. Tiger moth response reached a maximum at 475+/-344 ms
      from the end of the sequence; during the approach phase, well before the onset of
      the terminal buzz. In short, much of tiger moth response to bat attack occurs
      outside of the jamming hypotheses' predictions. Furthermore, no relationship
      exists between the duty cycle of a tiger moth's call (and thus the call's
      probability of jamming the bat) and its temporal response to bat attack. These
      data call into doubt the assumptions behind the jamming hypothesis as currently
      stated but do not directly test the functionality of arctiid sounds in disrupting
      echolocation in bat-moth aerial battles.

PMID- 16809456
TI  - A novel secreted endonuclease from Culex quinquefasciatus salivary glands.
AB  - Previous analysis of the salivary gland transcriptome of Culex quinquefasciatus
      showed the potential presence of an endonuclease with sequence similarities to
      shrimp, crab and two tsetse salivary proteins. Indeed, not only was the cloned
      cDNA shown to encode an active double-stranded endonuclease, but also the same
      activity was demonstrated to be secreted by salivary glands of Cx.
      quinquefasciatus. Preliminary studies with salivary gland extracts confirmed the
      presence of a highly active nuclease. This enzyme was shown to be present in the
      saliva of female mosquitoes by allowing starved mosquitoes to probe DNA
      containing agarose gel. The recombinant Cx. quinquefasciatus endonuclease
      (CuquEndo) produced in mammalian cells showed no sequence specificity for DNA
      substrate except that it only cleaves double-stranded DNA. Recombinant Cx.
      quinquefasciatus endonuclease was active in the presence of Mg(2+) ions at pH 7.0
      8.0, but no endonuclease activity was detected in the presence of calcium ions.
      The final hydrolysis products of this enzyme, detected by ion exchange
      chromatography, yielded DNA fragments ranging form 8-12 base pairs. Although
      endonucleases have been associated with a variety of cellular functions, their
      role in mosquito saliva is not clear. This female-specific secreted endonuclease
      may assist blood meal intake by lowering the local viscosity created by the
      release of host DNA in the bite site and/or acting as an indirect anticoagulant
      factor by producing a defibrotide-like mixture of DNA haptamers.

PMID- 16809457
TI  - The cellular response to heat stress in the goby Gillichthys mirabilis: a cDNA
      microarray and protein-level analysis.
AB  - The cellular response to stress relies on the rapid induction of genes encoding
      proteins involved in preventing and repairing macromolecular damage incurred as a
      consequence of environmental insult. To increase our understanding of the scope
      of this response, a cDNA microarray, consisting of 9207 cDNA clones, was used to
      monitor gene expression changes in the gill and white muscle tissues of a
      eurythermic fish, Gillichthys mirabilis (Gobiidae) exposed to ecologically
      relevant heat stress. In each tissue, the induction or repression of over 200
      genes was observed. These genes are associated with numerous biological
      processes, including the maintenance of protein homeostasis, cell cycle control,
      cytoskeletal reorganization, metabolic regulation and signal transduction, among
      many others. In both tissues, the molecular chaperones, certain transcription
      factors and a set of additional genes with various functions were induced in a
      similar manner; however, the majority of genes displayed tissue-specific
      responses. In gill, thermal stress induced the expression of the major structural
      components of the cytoskeleton, whereas these same genes did not respond to heat
      in muscle. In muscle, many genes involved in promoting cell growth and
      proliferation were repressed, perhaps to conserve energy for repair and
      replacement of damaged macromolecules, but a similar repression was not observed
      in the gill. Many of the observed changes in gene expression were similar to
      those described in model species whereas many others were unexpected.
      Measurements of the concentrations of the protein products of selected genes
      revealed that in each case an induction in mRNA synthesis correlated with an
      increase in protein production, though the timing and magnitude of the increase
      in protein was not consistently predicted by mRNA concentration, an important
      consideration in assessing the condition of the stressed cell using
      transcriptomic analysis.

PMID- 16809459
TI  - Performance-enhancing role of dietary fatty acids in a long-distance migrant
      shorebird: the semipalmated sandpiper.
AB  - At the end of summer, semipalmated sandpipers (Calidris pusilla) traveling from
      the Arctic stop in the Bay of Fundy (east coast of Canada) to build large fat
      reserves before a non-stop flight to South America. During a 2-week stopover, the
      body mass of this small shorebird is doubled ( approximately 20 g to 40 g) by
      feeding on a burrowing amphipod, Corophium volutator, that contains unusually
      high levels of n-3 polyunsaturated fatty acids (PUFA). In mammals, high n-3 PUFA
      content of membrane phospholipids (PL) is linked to improved exercise performance
      due to increased membrane fluidity that accelerates transmembrane lipid
      transport. We hypothesized that dietary n-3 PUFA could be used as a natural
      ;performance-enhancing substance' by semipalmated sandpipers to prepare their
      flight muscles for migration. Also, PUFA stored as fuel in neutral lipids (NL)
      can be mobilized more quickly than saturated fatty acids, but they contain less
      energy per unit mass. It is therefore unclear whether dietary fatty acids are
      modified before storage. Birds were collected at various stages of fat loading to
      examine changes in the composition of tissue PL (membranes) and NL (fuel stores).
      Results show that dietary n-3 PUFA are incorporated in tissue lipids in less than
      2 weeks. During the stopover, the double bond index of muscle PL increases by 25%
      and the fatty acid profiles of both muscle PL and adipose NL converge with that
      of the diet. However, >50% of dietary n-3 PUFA are converted to other fatty acids
      before storage, mainly to oleate (18:1), possibly because monounsaturates offer a
      compromise between high energy density and ease of mobilization. This study shows
      that long-distance migrant birds can (1) use natural diets rich in specific
      lipids to prime flight muscles for endurance exercise, and (2) modify dietary
      fatty acids before storing them as fuel.

PMID- 16809458
TI  - Mitochondrial proton leak rates in the slow, oxidative myotomal muscle and liver
      of the endothermic shortfin mako shark (Isurus oxyrinchus) and the ectothermic
      blue shark (Prionace glauca) and leopard shark (Triakis semifasciata).
AB  - Mitochondrial proton leak was assessed as a potential heat source in the slow,
      oxidative (red) locomotor muscle and liver of the shortfin mako shark (Isurus
      oxyrinchus), a regional endotherm that maintains the temperature of both tissues
      elevated above ambient seawater temperature. We hypothesized that basal proton
      leak rates in red muscle and liver mitochondria of the endothermic shortfin mako
      shark would be greater than those of the ectothermic blue shark (Prionace glauca)
      and leopard shark (Triakis semifasciata). Respiration rate and membrane potential
      in isolated mitochondria were measured simultaneously at 20 degrees C using a
      Clark-type oxygen electrode and a lipophilic probe (triphenylmethylphosphonium,
      TPMP(+)). Succinate-stimulated respiration was titrated with inhibitors of the
      electron transport chain, and the non-linear relationship between respiration
      rate and membrane potential was quantified. Mitochondrial densities of both
      tissues were measured by applying the point-contact method to electron
      micrographs so that proton leak activity of the entire tissue could be assessed.
      In all three shark species, proton leak occurred at a higher rate in red muscle
      mitochondria than in liver mitochondria. For each tissue, the proton leak curves
      of the three species overlapped and, at a membrane potential of 160 mV,
      mitochondrial proton leak rate (nmol H(+) min(-1) mg(-1) protein) did not differ
      significantly between the endothermic and ectothermic sharks. This finding
      indicates that red muscle and liver mitochondria of the shortfin mako shark are
      not specialized for thermogenesis by having a higher proton conductance. However,
      mako mitochondria did have higher succinate-stimulated respiration rates and
      membrane potentials than those of the two ectothermic sharks. This means that
      under in vivo conditions mitochondrial proton leak rates may be higher in the
      mako than in the ectothermic species, due to greater electron transport activity
      and a larger proton gradient driving proton leak. We also estimated each tissue's
      total proton leak by combining mitochondrial proton leak rates at 160 mV and
      tissue mitochondrial density data with published values of relative liver or red
      muscle mass for each of the three species. In red muscle, total proton leak was
      not elevated in the mako shark relative to the two ectothermic species. In the
      liver, total proton leak would be higher in the mako shark than in both
      ectothermic species, due to a lower proton conductance in the blue shark and a
      lower liver mitochondrial content in the leopard shark, and thus may contribute
      to endothermy.

PMID- 16809460
TI  - Characterization of diurnal urea excretion in the mangrove killifish, Rivulus
      marmoratus.
AB  - An unusual characteristic of nitrogen excretion in the ammoniotelic mangrove
      killifish Rivulus marmoratus is that urea is excreted (J(urea)) in a distinct
      diurnal pattern, whereas ammonia is excreted (J(amm)) at a steady rate. In this
      study we tested the hypothesis that the diurnal pattern in R. marmoratus is an
      endogenously generated pattern that is characterized as a circadian rhythm. This
      hypothesis was tested by measuring J(urea) and J(amm) following manipulation of
      feeding or lighting regimes. The diurnal J(urea) pattern in food-deprived R.
      marmoratus had a 24 h periodicity under normal conditions of 12 h:12 h light:dark
      (12:12 L:D) with 72% more urea excreted during 12:00 h and 18:00 h. In contrast,
      there was no significant pattern in J(amm). Fed fish (12:12 L:D) demonstrated a
      diurnal pattern in both J(urea) and J(amm) with up to an eightfold increase in
      excretion rates compared with rates obtained from food-deprived fish. Patterns of
      J(urea) were free running with a 24 h period under conditions of continuous
      darkness (0:24 L:D). Exposure to an inverse photoperiod (12:12 D:L) resulted in
      entrainment of the J(urea) pattern to the new photoperiod, with the highest rates
      of excretion occurring during midday of the new photoperiod. In contrast to R.
      marmoratus, nitrogen excretion rates in the zebrafish Danio rerio remained
      constant over time. The results of this study show that J(urea) in R. marmoratus
      demonstrates the characteristics of a circadian rhythm: a 24 h periodicity, a
      free-running rhythm in continuous conditions, and entrainment to new
      photoperiods.

PMID- 16809461
TI  - Metabolic and neuroendocrine effects on diurnal urea excretion in the mangrove
      killifish Rivulus marmoratus.
AB  - In mangrove killifish Rivulus marmoratus, urea excretion (J(urea)) follows a
      distinct diurnal pattern with the highest rates between 12:00 h and 18:00 h. We
      investigated the regulating mechanisms that underlie temporal rhythms in J(urea)
      in R. marmoratus. We hypothesized that the daily pattern of J(urea) in R.
      marmoratus is (1) due to diurnal changes in urea synthesis rates and ultimately
      metabolic rate and/or (2) controlled by neuroendocrine messengers. Oxygen
      consumption and whole body urea content in R. marmoratus demonstrated a clear
      diurnal pattern with maximum rates for both parameters occurring at 12:00 h. A
      strong synchrony between diurnal patterns of oxygen consumption, whole body urea
      content and J(urea) implicated metabolic regulation of the diurnal J(urea)
      pattern. Ketanserin, a 5-HT(2) receptor antagonist, and RU-486, a cortisol
      receptor antagonist, were used to test the second hypothesis. Increasing
      antagonist concentrations of either ketanserin or RU-486 resulted in dose
      dependent decreases in J(urea). Application of a single dose of either antagonist
      significantly decreases J(urea) for up to 12 and 6 h for ketanserin and RU-48,
      respectively. Repeated exposure to doses of either ketanserin or RU-486 did not
      abolish the diurnal pattern in J(urea); however, there was a significant decrease
      in the amplitude of the rates. Taken together, these findings indicate that the
      diurnal pattern of J(urea) in R. marmoratus are regulated by both metabolic and
      neuroendocrine factors. We propose that cortisol and 5-HT influence the absolute
      rate of urea excretion by altering the permeability of the gill membrane to urea
      and/or the rate of urea synthesis.

PMID- 16809463
TI  - Acoustic radiation from the head of echolocating harbor porpoises (Phocoena
      phocoena).
AB  - An experiment was conducted to investigate the sound pressure patterns on the
      melon of odontocetes by using four broadband hydrophones embedded in suction cups
      to measure echolocation signals on the surface of the forehead of two harbor
      porpoises (Phocoena phocoena). It has long been hypothesized that the special
      lipids found in the melon of odontocetes, and not in any other mammals, focus
      sounds produced in the nasal region that then propagate through the melon,
      producing a beam that is directional in both the horizontal and vertical planes.
      The results of our measurements supported the melon-focusing hypothesis, with the
      maximum click amplitude, representing the axis of the echolocation beam, located
      approximately 5.6-6.1 cm from the edge of the animal's upper lip along the
      midline of the melon. The focusing is not sharp but is sufficient to produce a
      transmission beam of about 16 degrees. Click amplitude dropped off rapidly at
      locations away from the location of site of maximum amplitude. Based on
      comparisons of forehead anatomy from similar sized porpoises, the beam axis
      coincided with a pathway extending from the phonic lips through the axis of the
      low-density/low sound velocity lipid core of the melon. The significant
      interaction between click number and hydrophone position suggests that the
      echolocation signals can take slightly different pathways through the melon,
      probably as a result of how the signals are launched by the production mechanism
      and the position of the acoustically reflective air sacs.

PMID- 16809462
TI  - Multidimensional analysis of suction feeding performance in fishes: fluid speed,
      acceleration, strike accuracy and the ingested volume of water.
AB  - Suction feeding fish draw prey into the mouth using a flow field that they
      generate external to the head. In this paper we present a multidimensional
      perspective on suction feeding performance that we illustrate in a comparative
      analysis of suction feeding ability in two members of Centrarchidae, the
      largemouth bass (Micropterus salmoides) and bluegill sunfish (Lepomis
      macrochirus). We present the first direct measurements of maximum fluid speed
      capacity, and we use this to calculate local fluid acceleration and volumetric
      flow rate. We also calculated the ingested volume and a novel metric of strike
      accuracy. In addition, we quantified for each species the effects of gape
      magnitude, time to peak gape, and swimming speed on features of the ingested
      volume of water. Digital particle image velocimetry (DPIV) and high-speed video
      were used to measure the flow in front of the mouths of three fish from each
      species in conjunction with a vertical laser sheet positioned on the mid-sagittal
      plane of the fish. From this we quantified the maximum fluid speed (in the
      earthbound and fish's frame of reference), acceleration and ingested volume. Our
      method for determining strike accuracy involved quantifying the location of the
      prey relative to the center of the parcel of ingested water. Bluegill sunfish
      generated higher fluid speeds in the earthbound frame of reference, accelerated
      the fluid faster, and were more accurate than largemouth bass. However,
      largemouth bass ingested a larger volume of water and generated a higher
      volumetric flow rate than bluegill sunfish. In addition, because largemouth bass
      swam faster during prey capture, they generated higher fluid speeds in the fish's
      frame of reference. Thus, while bluegill can exert higher drag forces on
      stationary prey items, largemouth bass more quickly close the distance between
      themselves and prey. The ingested volume and volumetric flow rate significantly
      increased as gape increased for both species, while time to peak gape had little
      effect on the volume. However, peak gape distance did not affect the maximum
      fluid speed entering the mouth for either species. We suggest that species that
      generate high fluid speeds in the earthbound frame of reference will commonly
      exhibit small mouths and a high capacity to deliver force to buccal expansion,
      while species that ingest a large volume of water and generate high volumetric
      flow rates will have larger buccal cavities and cranial expansion linkage systems
      that favor displacement over force delivery.

PMID- 16809464
TI  - Effects of moderate and substantial hypoxia on erythropoietin levels in rainbow
      trout kidney and spleen.
AB  - Erythropoietin (EPO) is a glycoprotein hormone that regulates the proliferation
      and differentiation of erythroid progenitor cells in mammals. Although EPO has
      been identified in fish, the specific function and effects of hypoxia have not
      been investigated previously. In this study, we have demonstrated a relationship
      between increases in renal EPO levels and decreases in spleen EPO levels and
      spleen-somatic index (SSI), with increases in haemoglobin (Hb) concentration in
      the blood during hypoxia exposure in rainbow trout. Splenic contraction and the
      subsequent red blood cell release accounts for the initial increase in Hb
      concentration in the blood, whereas EPO action probably accounts for the later
      increases in hemoglobin concentration in the blood. Our data indicate that fish
      and mammalian erythropoietic systems are similar in response to hypoxia, in that
      erythropoiesis in fish is influenced by EPO.

PMID- 16809465
TI  - Behavioral responses of Drosophila to biogenic levels of carbon dioxide depend on
      life-stage, sex and olfactory context.
AB  - Drosophila melanogaster (Meigen) detects and uses many volatiles for its
      survival. Carbon dioxide (CO(2)) is detected in adults by a special class of
      olfactory receptor neurons, expressing the gustatory receptor Gr21a. The
      behavioral responses to CO(2) were investigated in a four-field olfactometer
      bioassay that is new for Drosophila. We determined (1) whether the sensitivity of
      this response changes with odor context, and (2) if it depends on sex and life
      stage. When CO(2) was added to ambient air in one field and tested against
      ambient air in the three other fields, individually observed adults avoided CO(2)
      (0.1-1% above ambient), but did not respond to a low rise of 0.02%. We relate
      this behavior to measurements of CO(2) production in bananas and flies. When
      0.02% CO(2) was combined with the odor of apple cider vinegar in one field of the
      olfactometer and tested against ambient air in the three other fields, the
      addition of CO(2) did not affect the attractiveness of apple cider vinegar alone.
      However, this combination of CO(2) and vinegar became repellent when it was
      tested against vinegar at ambient CO(2) concentrations in the three other fields.
      This ;odor background effect' was female-specific, revealing a sexually dimorphic
      behavior. The new assay allowed us to test larvae under similar conditions and
      compare their behavior to that of adults. Like adults, they avoided CO(2), but
      with lower sensitivity. Larvae lacking neurons expressing Gr21a lost their
      avoidance behavior to CO(2), but kept their positive response to vinegar odor.
      Hence, Gr21a-expressing neurons mediate similar behaviors in larvae and adults.

PMID- 16809466
TI  - Dopamine modulation of Ca(2+) dependent Cl(-) current regulates ciliary beat
      frequency controlling locomotion in Tritonia diomedea.
AB  - The physiological mechanisms controlling ciliary beating remain largely unknown.
      Evidence exists supporting both hormonal control of ciliary beating and control
      via direct innervation. In the present study we investigated nervous control of
      cilia based locomotion in the nudibranch mollusc, Tritonia diomedea. Ciliated
      pedal epithelial (CPE) cells acting as locomotory effectors may be electrically
      excitable. To explore this possibility we characterized the cells' electrical
      properties, and found that CPE cells have large voltage dependent whole cell
      currents with two components. First, there is a fast activating outward Cl(-)
      current that is both voltage and Ca(2+) influx dependent (I(Cl(Ca))). I(Cl(Ca))
      is sensitive to DIDS and 9-AC, and resembles currents of Ca(2+)-activated Cl(-)
      channels (CaCC). Ca(2+) dependence also suggests the presence of voltage-gated
      Ca(2+) channels; however, we were unable to detect these currents. The second
      current, a voltage dependent proton current (I(H)), activates very slowly and is
      sensitive to both Zn(2+) and changes in pH. In addition we identify a new cilio
      excitatory substance in Tritonia, viz., dopamine. Dopamine, in the 10 mumol l(-1)
      1 mmol l(-1) range, significantly increases ciliary beat frequency (CBF). We also
      found dopamine and Tritonia Pedal Peptide (TPep-NLS) selectively suppress
      I(Cl(Ca)) in CPE cells, demonstrating a link between CBF excitation and
      I(Cl(Ca)). It appears that dopamine and TPep-NLS inhibit I(Cl(Ca)) not through
      changing [Ca(2+)](in), but directly by an unknown mechanism. Coupling of
      I(Cl(Ca)) and CBF is further supported by our finding that DIDS and zero [Cl(
      )](out) both increase CBF, mimicking dopamine and TPep-NLS excitation. These
      results suggest that dopamine and TPep-NLS act to inhibit I(Cl(Ca)), initiating
      and prolonging Ca(2+) influx, and activating CBF excitation.

PMID- 16809467
TI  - Nervous control of ciliary beating by Cl(-), Ca(2+) and calmodulin in Tritonia
      diomedea.
AB  - In vertebrates, motile cilia line airways, oviducts and ventricles. Invertebrate
      cilia often control feeding, swimming and crawling, or gliding. Yet control and
      coordination of ciliary beating remains poorly understood. Evidence from the
      nudibranch mollusc, Tritonia diomedea, suggests that locomotory ciliated
      epithelial cells may be under direct electrical control. Here we report that
      depolarization of ciliated pedal epithelial (CPE) cells increases ciliary beating
      frequency (CBF), and elicits CBF increases similar to those caused by dopamine
      and the neuropeptide, TPep-NLS. Further, four CBF stimulants (zero external Cl(
      ), depolarization, dopamine and TPep-NLS) depend on a common mode of action, viz.
      Ca(2+) influx, possibly through voltage-gated Ca(2+) channels, and can be blocked
      by nifedipine. Ca(2+) influx alone, however, does not provide all the internal
      Ca(2+) necessary for CBF change. Ryanodine receptor (RyR) channel-gated internal
      stores are also necessary for CBF excitation. Caffeine can stimulate CBF and is
      sensitive to the presence of the RyR blocker dantrolene. Dantrolene also reduces
      CBF excitation induced by dopamine and TPep-NLS. Finally, W-7 and calmidazolium
      both block CBF excitation by caffeine and dopamine, and W-7 is effective at
      blocking TPep-NLS excitation. The effects of calmidazolium and W-7 suggest a role
      for Ca(2+)-calmodulin in regulating CBF, either directly or via Ca(2+)-calmodulin
      dependent kinases or phosphodiesterases. From these results we hypothesize
      dopamine and TPep-NLS induce depolarization-driven Ca(2+) influx and Ca(2+)
      release from internal stores that activates Ca(2+)-calmodulin, thereby increasing
      CBF.

PMID- 16809468
TI  - Division of labor in the honey bee (Apis mellifera): the role of tyramine beta
      hydroxylase.
AB  - The biogenic amine octopamine (OA) is involved in the regulation of honey bee
      behavioral development; brain levels are higher in foragers than bees working in
      the hive, especially in the antennal lobes, and treatment causes precocious
      foraging. We measured brain mRNA and protein activity of tyramine beta
      hydroxylase (T betah), an enzyme vital for OA synthesis, in order to begin
      testing the hypothesis that this enzyme is responsible for the rising levels of
      OA during honey bee behavioral development. Brain OA levels were greater in
      forager bees than in bees engaged in brood care, as in previous studies, but T
      betah activity was not correlated with bee behavior. T betah mRNA levels,
      however, did closely track OA levels during behavioral development, and T betah
      mRNA was localized to previously identified octopaminergic neurons in the bee
      brain. Our results show that the transcription of this neurotransmitter synthetic
      enzyme is associated with regulation of social behavior in honey bees, but other
      factors may be involved.

PMID- 16809469
TI  - Dopaminergic regulation of ion transport in gills of the euryhaline
      semiterrestrial crab Chasmagnathus granulatus: interaction between D1- and D2
      like receptors.
AB  - The effects of dopamine (DA) and dopaminergic agonists and antagonists on ion
      transport were studied in isolated perfused gills of the crab Chasmagnathus
      granulatus. DA applied under steady state conditions (perfusion with hemolymph
      like saline) produced a transient increase of the transepithelial potential
      difference (V(te)) from 2.2+/-0.2 to 4.8+/-0.3 mV, describing an initial cAMP
      dependent stimulating phase followed by an inhibitory phase. Spiperone and
      domperidone (antagonists of D2-like DA receptors in vertebrates) completely
      blocked the response to DA, while the D1-like antagonist SCH23390 blocked only
      the inhibitory phase. Theophylline (phosphodiesterase inhibitor) and okadaic acid
      (protein phosphatases PP1 and PP2A inhibitor) were also able to block the
      inhibitory phase, suggesting that it depends on adenylyl cyclase inhibition and
      on protein phosphatases. When the gills were perfused with hypo-osmotic solution,
      or with the adenylyl cyclase activator forskolin, V(te) was increased several
      fold. DA applied under these stimulated conditions partially reversed the V(te)
      increase by 54% and 25%, respectively. Similarly, the D1-like agonist,
      fenoldopam, produced a 33% reduction in the stimulated V(te). We propose that, in
      C. granulatus gills, DA stimulates adenylyl cyclase and therefore ion transport
      through D1-like receptors linked to a Gs protein, although they respond to
      antagonists that interact with D2-like receptors in vertebrates. The inhibitory
      phase seems to be mediated by D2-like receptors linked to a Gi/o protein, which
      inhibits adenylyl cyclase, although these receptors can be activated or blocked
      by agonists or antagonists that interact with D1-like receptors in vertebrates
      and insects.

PMID- 16809470
TI  - Evidence for a role of orcokinin-related peptides in the circadian clock
      controlling locomotor activity of the cockroach Leucophaea maderae.
AB  - The accessory medulla (AMe), a small neuropil in the optic lobe, houses the
      master circadian clock in the brain of the cockroach Leucophaea maderae and
      controls circadian rhythms in locomotor activity. Recently, members of the
      orcokinin family of crustacean neuropeptides were identified in a cockroach and a
      locust and were shown by immunocytochemistry to be prominently present in the
      AMe. In the cockroach L. maderae, about 30 neurons in five of six established
      cell groups of the AMe showed orcokinin immunostaining. By means of tracer
      injections into one AMe and immunostaining with anti-orcokinin antiserum, we show
      here that one orcokinin-immunoreactive ventral neuron and three ventromedian
      neurons directly connect both AMae. To determine a possible circadian function of
      orcokinin in the cockroach, we injected 150 fmol Asn(13)-orcokinin into the
      vicinity of the AMe at different circadian times. These experiments resulted in
      stable phase-dependent phase shifts of circadian locomotor activity of the
      cockroach. The shape of the resulting phase-response curve closely matched the
      phase-shifting effects of light pulses, and its amplitude was dependent on the
      amount of the injected peptide. Together with the anatomical data, the results
      suggest that orcokinin-related peptides play an important role in light
      entrainment pathways to the circadian clock via the contralateral compound eye.
      This study, furthermore, provides the first evidence for a physiological role of
      an orcokinin-related peptide in insects.

PMID- 16809471
TI  - Nitric oxide and cnidarian bleaching: an eviction notice mediates breakdown of a
      symbiosis.
AB  - Nitric oxide (NO) is a free radical implicated in numerous cell signaling,
      physiological and pathophysiological processes of eukaryotic cells. Here, we
      describe the production of NO as part of the cellular stress response of the
      symbiotic sea anemone Aiptasia pallida, which hosts dinoflagellates from the
      genus Symbiodinium. We show that exposure to elevated temperatures induces
      symbiotic anemones to produce high levels of NO, leading to the collapse of the
      symbiosis. These results shed light on the poorly understood cellular mechanism
      through which elevated seawater temperature causes the release of symbiotic algae
      from symbiotic cnidarians, a detrimental process known as coral (cnidarian)
      bleaching. The results presented here show that the host cell is a major source
      of NO during exposure to elevated temperatures and that this constitutes a
      cytotoxic response leading to bleaching. These results have important
      evolutionary implications as the observed NO production in these basal metazoans
      displays many parallels to the cytotoxic inflammatory response to pathogens, a
      well-understood process in mammalian model systems.

PMID- 16809472
TI  - The fight against tuberculosis.

PMID- 16809473
TI  - Loss of caspase-8 in tumor cells: mechanism to overcome integrin-mediated death?

PMID- 16809474
TI  - Pin-pointing APP processing.

PMID- 16809475
TI  - Cancer stem cells: redefining the paradigm of cancer treatment strategies.
AB  - Cancer has been known to arise from long-lived cells in the body and to possess
      properties in common with undifferentiated, embryonic cells. Recent findings of a
      population of cells in solid tumors resembling stem cells supports a stem cell
      model of cancer. A scheme in which all cancers initiate from "activated' stem
      cells helps bring together data from genetic, cell biology, and epidemiology
      studies. Cancer can arise from embryonic cells in the case of childhood tumors;
      hormone-activated stem cells in the case of breast cancer; and following chronic
      activation of stem cells caused by tissue damage. This scheme helps explain the
      failure of many cancer therapies, points out deficiencies in certain research
      approaches, and focuses the problem on a subset of cells that can be explicitly
      targeted, leading to more efficient therapy.

PMID- 16809477
TI  - The antidepressant -like effects of delta-opioid receptor agonists.
AB  - Activation of the delta-opioid receptor (DOR) system produces an interesting
      behavioral profile distinct from that of other opioids. Unlike mu- and kappa
      opioid agonists, delta-opioid agonists alone have limited pain-relieving
      qualities as measured in morphine-sensitive antinociceptive assays. Recent
      evidence, however, suggests that the DOR system may play a role in regulating
      mood and emotional states. For example, DOR activation stimulates robust
      antidepressant-like effects in preclinical assays, suggesting that these
      compounds may have therapeutic potential for treating human depression. This
      review discusses the role of the DORs in depression and the antidepressant-like
      effects of delta-opioid agonists as well as their limitations.

PMID- 16809476
TI  - Cannabinoids biology: the search for new therapeutic targets.
AB  - Cannabinoids, in the form of marijuana plant extracts, have been used for
      thousands of years for a wide variety of medical conditions, ranging from general
      malaise and mood disorders to more specific ailments, such as pain, nausea, and
      muscle spasms. The discovery of tetrahydrocannabinol, the active principal in
      marijuana, and the identification and cloning of two cannabinoid receptors (i.e.,
      CB1 and CB2) has subsequently led to biomedical appreciation for a family of
      endocannabinoid lipid transmitters. The biosynthesis and catabolism of the
      endocannabinoids and growing knowledge of their broad physiological roles are
      providing insight into potentially novel therapeutic targets. Compounds directed
      at one or more of these targets may allow for cannabinoid-based therapeutics with
      limited side effects and abuse liability.

PMID- 16809478
TI  - Human organic anion transporter 3 gene is regulated constitutively and inducibly
      via a cAMP-response element.
AB  - Human organic anion transporter (OAT) 3 (SLC22A8) is localized to the basolateral
      membranes of renal tubular epithelial cells and plays a critical role in the
      excretion of anionic compounds. We previously reported that interindividual
      variation in the OAT3 mRNA level corresponded to interindividual differences in
      the rate of renal excretion of cefazolin. However, there is little information
      available on the molecular mechanisms regulating the gene expression of OAT3.
      Therefore, in the present study, we examined the transcriptional regulation of
      human OAT3. A deletion analysis of the OAT3 promoter suggested that the region
      spanning -214 to -77 base pairs was essential for basal transcriptional activity.
      This region contained a perfectly conserved cAMP-response element (CRE), and a
      mutation here led to a reduction in promoter activity. Electrophoretic mobility
      shift assays showed that CRE-binding protein (CREB)-1 and activating
      transcription factor (ATF)-1 bound to CRE. The activity of the OAT3 promoter was
      increased through the phosphorylation of CREB-1 and ATF-1 by treatment with 8
      bromo-cAMP. This paper reports the first characterization of the human OAT3
      promoter and shows that CREB-1 and ATF-1 function as constitutive and inducible
      transcriptional regulators of the human OAT3 gene via CRE.

PMID- 16809479
TI  - Peripheral phosphodiesterase 4 inhibition produced by 4-[2-(3,4-Bis
      difluoromethoxyphenyl)-2-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-phenyl]
      ethyl]-3-methylpyridine-1-oxide (L-826,141) prevents experimental autoimmune
      encephalomyelitis.
AB  - Administration of phosphodiesterase 4 (PDE4) inhibitors suppresses the
      pathogenesis associated with experimental autoimmune encephalomyelitis (EAE), an
      animal model of multiple sclerosis (MS). In the present study, we compared the
      effects of rolipram and 4-[2-(3,4-bis-difluoromethoxyphenyl)-2-[4-(1,1,1,3,3,3
      hexafluoro-2-hydroxypropan-2-yl)-phenyl]-ethyl]-3-methylpyridine-1-oxide (L
      826,141), a novel nonbrain penetrant PDE4 inhibitor, on the onset and severity of
      clinical signs in a chronic, nonrelapsing/remitting model of EAE. Both rolipram
      (10 mg/kg p.o.) and L-826,141 (3 mg/kg p.o.) reduced the severity of EAE relative
      to controls, whereas L-826,141 (3 mg/kg p.o.) also delayed disease onset. To
      assess whether L-826,141 prevented EAE progression after the first signs of
      clinical onset, rolipram (10 mg/kg p.o.) or L-826,141 (3 or 30 mg/kg p.o.) were
      administered 24 h after the first signs of EAE were observed. Only L-826,141 at a
      dose of 30 mg/kg p.o. significantly decreased the clinical severity of EAE
      compared with vehicle controls. Immunohistochemical detection of the neuronal
      activity marker Fos confirmed that L-826,141 did not reach concentrations in the
      central nervous system sufficient to activate central neurons. Lipopolysaccharide
      induced tumor necrosis factor-alpha in whole blood and plasma concentrations of L
      826,141 revealed that only the 30-mg/kg dose resulted in levels sufficient to
      produce a near complete inhibition of PDE4 activity in immune cells. Taken
      together, these results demonstrate that peripheral PDE4 inhibition, produced by
      L-826,141, prevents the progression of EAE after the first onset of clinical
      signs, and suggest that similar compounds may have clinical efficacy in the
      treatment of MS.

PMID- 16809480
TI  - Expression and transport activity of breast cancer resistance protein
      (Bcrp/Abcg2) in dually perfused rat placenta and HRP-1 cell line.
AB  - Breast cancer resistance protein (BCRP/ABCG2) is a member of the ATP-binding
      cassette transporter family that recognizes a variety of chemically unrelated
      compounds. Its expression has been revealed in many mammal tissues, including
      placenta. The purpose of this study was to describe its role in transplacental
      pharmacokinetics using rat placental HRP-1 cell line and dually perfused rat
      placenta. In HRP-1 cells, expression of Bcrp, but not P-glycoprotein, was
      revealed at mRNA and protein levels. Cell accumulation studies confirmed Bcrp
      dependent uptake of BODIPY FL prazosin. In the placental perfusion studies, a
      pharmacokinetic model was applied to distinguish between passive and Bcrp
      mediated transplacental passage of cimetidine as a model substrate. Bcrp was
      shown to act in a concentration-dependent manner and to hinder maternal-to-fetal
      transport of the drug. Fetal-to-maternal clearance of cimetidine was found to be
      25 times higher than that in the opposite direction; this asymmetry was partly
      eliminated by BCRP inhibitors fumitremorgin C (2 microM) or N-(4-[2-(1,2,3,4
      tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9
      oxo-4-acridine carboxamide (GF120918; 2 microM) and abolished at high cimetidine
      concentrations (1000 microM). When fetal perfusate was recirculated, Bcrp was
      found to actively remove cimetidine from the fetal compartment to the maternal
      compartment even against a concentration gradient and to establish a 2-fold
      maternal-to-fetal concentration ratio. Based on our results, we propose a two
      level defensive role of Bcrp in the rat placenta in which the transporter 1)
      reduces passage of its substrates from mother to fetus but also 2) removes the
      drug already present in the fetal circulation.

PMID- 16809482
TI  - Hypothermia modulates circadian clock gene expression in lizard peripheral
      tissues.
AB  - The molecular mechanisms whereby the circadian clock responds to temperature
      changes are poorly understood. The ruin lizard Podarcis sicula has historically
      proven to be a valuable vertebrate model for exploring the influence of
      temperature on circadian physiology. It is an ectotherm that naturally
      experiences an impressive range of temperatures during the course of the year.
      However, no tools have been available to dissect the molecular basis of the clock
      in this organism. Here, we report the cloning of three lizard clock gene homologs
      (Period2, Cryptochrome1, and Clock) that have a close phylogenetic relationship
      with avian clock genes. These genes are expressed in many tissues and show a
      rhythmic expression profile at 29 degrees C in light-dark and constant darkness
      lighting conditions, with phases comparable to their mammalian and avian
      counterparts. Interestingly, we show that at low temperatures (6 degrees C),
      cycling clock gene expression is attenuated in peripheral clocks with a
      characteristic increase in basal expression levels. We speculate that this
      represents a conserved vertebrate clock gene response to low temperatures.
      Furthermore, these results bring new insight into the issue of whether circadian
      clock function is compatible with hypothermia.

PMID- 16809481
TI  - White adipose tissue lacks significant vagal innervation and immunohistochemical
      evidence of parasympathetic innervation.
AB  - Converging evidence indicates that white adipose tissue (WAT) is innervated by
      the sympathetic nervous system (SNS) based on immunohistochemical labeling of a
      SNS marker (tyrosine hydroxylase [TH]), tract tracing of WAT sympathetic
      postganglionic innervation, pseudorabies virus (PRV) transneuronal labeling of
      WAT SNS outflow neurons, and functional evidence from denervation studies.
      Recently, WAT para-SNS (PSNS) innervation was suggested because local surgical
      WAT sympathectomy (sparing hypothesized parasympathetic innervation) followed by
      PRV injection yielded infected cells in the vagal dorsomotor nucleus (DMV), a
      traditionally-recognized PSNS brain stem site. In addition, local surgical PSNS
      WAT denervation triggered WAT catabolic responses. We tested histologically
      whether WAT was parasympathetically innervated by searching for PSNS markers in
      rat, and normal (C57BL) and obese (ob/ob) mouse WAT. Vesicular acetylcholine
      transporter, vasoactive intestinal peptide and neuronal nitric oxide synthase
      immunoreactivities were absent in WAT pads (retroperitoneal, epididymal, inguinal
      subcutaneous) from all animals. Nearly all nerves innervating WAT vasculature and
      parenchyma that were labeled with protein gene product 9.5 (PGP9.5; pan-nerve
      marker) also contained TH, attesting to pervasive SNS innervation. When Siberian
      hamster inguinal WAT was sympathetically denervated via local injections of
      catecholaminergic toxin 6-hydroxydopamine (sparing putative parasympathetic
      nerves), subsequent PRV injection resulted in no central nervous system (CNS) or
      sympathetic chain infections suggesting no PSNS innervation. By contrast, vehicle
      injected WAT subsequently inoculated with PRV had typical CNS/sympathetic chain
      viral infection patterns. Collectively, these data indicate no parasympathetic
      nerve markers in WAT of several species, with sparse DMV innervation and question
      the claim of PSNS WAT innervation as well as its functional significance.

PMID- 16809483
TI  - Circulating interleukin-6 induces fever through a STAT3-linked activation of COX
      2 in the brain.
AB  - Interleukin (IL)-6 is an important humoral mediator of fever following infection
      and inflammation and satisfies a number of criteria for a circulating pyrogen.
      However, evidence supporting such a role is diminished by the moderate or even
      absent ability of the recombinant protein to induce fever and activate the
      cyclooxygenase-2 (COX-2) pathway in the brain, a prerequisite step in the
      initiation and maintenance of fever. In the present study, we investigated the
      role of endogenous circulating IL-6 in a rodent model of localized inflammation,
      by neutralizing its action using a specific antiserum (IL-6AS). Rats were
      injected with LPS (100 microg/kg) or saline into a preformed air pouch in
      combination with an intraperitoneal injection of either normal sheep serum or IL
      6AS (1.8 ml/rat). LPS induced a febrile response, which was accompanied by a
      significant rise in plasma IL-6 and nuclear STAT3 translocation in endothelial
      cells throughout the brain 2 h after treatment, including areas surrounding the
      sensory circumventricular organs and the median preoptic area (MnPO), important
      regions in mediating fever. These responses were abolished in the presence of the
      IL-6AS, which also significantly inhibited the LPS-induced upregulation of mRNA
      expression or immunoreactivity (IR) of the inducible form of COX, the rate
      limiting enzyme for PGE2-synthesis. Interestingly, nuclear signal transducer and
      activator of transcription (STAT)3-positive cells colocalized with COX-2-IR,
      signifying that IL-6-activated cells are directly involved in PGE2 production.
      These observations suggest that IL-6 is an important circulating pyrogen that
      activates the COX-2-pathway in cerebral microvasculature, most likely through a
      STAT3-dependent pathway.

PMID- 16809484
TI  - Prolactin and the expression of suppressor of cytokine signaling-3 in the sheep
      adrenal gland before birth.
AB  - The fetal pituitary-adrenal axis plays a key role in the fetal response to
      intrauterine stress and in the timing of parturition. The fetal sheep adrenal
      gland is relatively refractory to stimulation in midgestation (90-120 days)
      before the prepartum activation, which occurs around 135 days gestation
      (term=147+/-3 days). The mechanisms underlying the switch from adrenal quiescence
      to activation are unclear. Therefore, we have investigated the expression of
      suppressor of cytokine signaling-3 (SOCS-3), a putative inhibitor of tissue
      growth in the fetal sheep adrenal between 50 and 145 days gestation and in the
      adrenal of the growth-restricted fetal sheep in late gestation. SOCS-3 is
      activated by a range of cytokines, including prolactin (PRL), and we have,
      therefore, determined whether PRL administered in vivo or in vitro stimulates
      SOCS-3 mRNA expression in the fetal adrenal in late gestation. There was a
      decrease (P<0.005) in SOCS-3 expression in the fetal adrenal between 54 and 133
      days and between 141 and 144 days gestation. Infusion of the dopaminergic
      agonist, bromocriptine, which suppressed fetal PRL concentrations but did not
      decrease adrenal SOCS-3 mRNA expression. PRL administration, however,
      significantly increased adrenal SOCS-3 mRNA expression (P<0.05). Similarly, there
      was an increase (P<0.05) in SOCS-3 mRNA expression in adrenocortical cells in
      vitro after exposure to PRL (50 ng/ml). Placental and fetal growth restriction
      had no effect on SOCS-3 expression in the adrenal during late gestation. In
      summary, the decrease in the expression of the inhibitor SOCS-3 after 133 days
      gestation may be permissive for a subsequent increase in fetal adrenal growth
      before birth. We conclude that factors other than PRL act to maintain adrenal
      SOCS-3 mRNA expression before 133 days gestation but that acute elevations of PRL
      can act to upregulate adrenal SOCS-3 expression in the sheep fetus during late
      gestation.

PMID- 16809485
TI  - Oxyresveratrol dampens neuroimmune responses in vivo: a selective effect on TNF
      alpha.
AB  - Consumption of nutrients rich in hydroxystilbenes has been promoted because of
      their health benefits, including dampening of inflammatory responses. However,
      few studies have examined their effects in vivo. Here, we show that the
      hydroxystilbene oxyresveratrol (trans-2,3',4,5'-tetrahydroxystilbene: o-RES)
      blocked hypothermia but caused no significant effect on the febrile response to
      the immune stimulus, bacterial LPS in rats. This was associated with a reduction
      in the LPS-induced plasma cytokine, tumor necrosis factor (TNF)-alpha, but not IL
      6. Both IL-6-stimulated STAT-3 and LPS-induced cycoloxygenase-2 expression in the
      hypothalamus were not affected by o-RES. These data strongly suggest that the o
      RES-induced dampening of neuroimmune responses is largely due to its inhibitory
      effect on TNF-alpha production. In contrast to in vitro experiments, o-RES has no
      direct effect on NF-kappaB signaling pathway in vivo. The specific inhibitory
      effect of o-RES on TNF-alpha opens new avenues for the clinical use of o-RES in
      pathological conditions where excessive production of TNF-alpha is deleterious.

PMID- 16809486
TI  - Effects of sleep deprivation on the development of autoimmune disease in an
      experimental model of systemic lupus erythematosus.
AB  - Sleep is hypothesized to play a restorative role on immune system. In addition,
      disturbed sleep is thought to impair host defense mechanisms. Chronic sleep
      deprivation is a common occurrence in modern society and has been observed in a
      number of chronic inflammatory conditions, such as systemic lupus erythematosus
      (SLE). New Zealand Black/New Zealand White (NZB/NZW) F1 mice develop an
      autoimmune disease that strongly resembles SLE in humans, exhibiting high titers
      of antinuclear antibodies associated with the development of rapidly progressive
      and lethal glomerulonephritis. On the basis of this evidence, the present study
      examined the onset and progress of lupus in as-yet healthy female mice submitted
      to sleep deprivation. Sleep deprivation was accomplished by two 96-h periods in
      the multiple-platform method when mice were 10 wk old, and they were observed
      until 28 wk of age. Blood samples were collected from the orbital plexus
      fortnightly to evaluate serum antinuclear antibodies and anti-double-stranded
      DNA. Proteinuria and longevity as well as body weight were also assessed. The
      results indicated that mice submitted to sleep deprivation exhibited an earlier
      onset of the disease, as reflected by the increased number of antinuclear
      antibodies. However, no statistical difference was found in the other parameters
      analyzed. According to these results, sleep deprivation could be considered as a
      risk factor for the onset but not for the evolution of the disease.

PMID- 16809487
TI  - MC1R germline variants confer risk for BRAF-mutant melanoma.
AB  - Germline variants in MC1R, the gene encoding the melanocortin-1 receptor, and sun
      exposure increase risk for melanoma in Caucasians. The majority of melanomas that
      occur on skin with little evidence of chronic sun-induced damage (non-CSD
      melanoma) have mutations in the BRAF oncogene, whereas in melanomas on skin with
      marked CSD (CSD melanoma) these mutations are less frequent. In two independent
      Caucasian populations, we show that MC1R variants are strongly associated with
      BRAF mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma
      associated with MC1R is due to an increase in risk of developing melanomas with
      BRAF mutations.

PMID- 16809488
TI  - The Neurospora checkpoint kinase 2: a regulatory link between the circadian and
      cell cycles.
AB  - The clock gene period-4 (prd-4) in Neurospora was identified by a single allele
      displaying shortened circadian period and altered temperature compensation.
      Positional cloning followed by functional tests show that PRD-4 is an ortholog of
      mammalian checkpoint kinase 2 (Chk2). Expression of prd-4 is regulated by the
      circadian clock and, reciprocally, PRD-4 physically interacts with the clock
      component FRQ, promoting its phosphorylation. DNA-damaging agents can reset the
      clock in a manner that depends on time of day, and this resetting is dependent on
      PRD-4. Thus, prd-4, the Neurospora Chk2, identifies a molecular link that feeds
      back conditionally from circadian output to input and the cell cycle.

PMID- 16809492
TI  - Climate change. Yes, it's been getting warmer in here since the CO2 began to
      rise.

PMID- 16809491
TI  - Alarm bells should help us refocus.

PMID- 16809489
TI  - A distinct small RNA pathway silences selfish genetic elements in the germline.
AB  - In the Drosophila germline, repeat-associated small interfering RNAs (rasiRNAs)
      ensure genomic stability by silencing endogenous selfish genetic elements such as
      retrotransposons and repetitive sequences. Whereas small interfering RNAs
      (siRNAs) derive from both the sense and antisense strands of their double
      stranded RNA precursors, rasiRNAs arise mainly from the antisense strand. rasiRNA
      production appears not to require Dicer-1, which makes microRNAs (miRNAs), or
      Dicer-2, which makes siRNAs, and rasiRNAs lack the 2',3' hydroxy termini
      characteristic of animal siRNA and miRNA. Unlike siRNAs and miRNAs, rasiRNAs
      function through the Piwi, rather than the Ago, Argonaute protein subfamily. Our
      data suggest that rasiRNAs protect the fly germline through a silencing mechanism
      distinct from both the miRNA and RNA interference pathways.

PMID- 16809490
TI  - Netrins promote developmental and therapeutic angiogenesis.
AB  - Axonal guidance and vascular patterning share several guidance cues, including
      proteins in the netrin family. We demonstrate that netrins stimulate
      proliferation, migration, and tube formation of human endothelial cells in vitro
      and that this stimulation is independent of known netrin receptors. Suppression
      of netrin1a messenger RNA in zebrafish inhibits vascular sprouting, implying a
      proangiogenic role for netrins during vertebrate development. We also show that
      netrins accelerate neovascularization in an in vivo model of ischemia and that
      they reverse neuropathy and vasculopathy in a diabetic murine model. We propose
      that the attractive vascular and neural guidance functions of netrins offer a
      unique therapeutic potential.

PMID- 16809493
TI  - Avian influenza. Journal letter spotlights China's bird flu reporting.

PMID- 16809494
TI  - Avian influenza. Human transmission but no pandemic in Indonesia.

PMID- 16809496
TI  - ETHICS. Blocking a book, Dutch university rekindles furor over Nobelist Debye.

PMID- 16809495
TI  - War zone. Targeted for murder, Iraqi scientists named on a hit list.

PMID- 16809497
TI  - Diversity. Report urges national academies to improve status of women.

PMID- 16809498
TI  - PALEOCLIMATOLOGY. Atlantic mud shows how melting ice triggered an ancient chill.

PMID- 16809499
TI  - Animal behavior. Signs of empathy seen in mice.

PMID- 16809500
TI  - Chemistry. Sugary recipe boosts grow-your-own plastics.

PMID- 16809501
TI  - Mouse genetics. A mouse for every gene.

PMID- 16809502
TI  - Mouse genetics. NIH knocks out key mouse house.

PMID- 16809503
TI  - Mouse genetics. China takes aim at comprehensive mouse knockout program.

PMID- 16809505
TI  - Human Behavior and Evolution Society meeting. An evolutionary squeeze on brain
      size.

PMID- 16809504
TI  - Human Behavior and Evolution Society meeting. Long-ago peoples may have been long
      in the tooth.

PMID- 16809506
TI  - Cell biology. Podosomes and invadopodia help mobile cells step lively.

PMID- 16809508
TI  - Testing climate reconstructions.

PMID- 16809507
TI  - Water quality. High court asks Army Corps to measure value of wetlands.

PMID- 16809509
TI  - Team science and the NIBIB.

PMID- 16809510
TI  - Funding for young investigators at Whitaker.

PMID- 16809511
TI  - Caspase-10 in mouse or not?

PMID- 16809512
TI  - Role of iNOS in human host defense.

PMID- 16809513
TI  - Comment on "Ancient DNA from the first European farmers in 7500-year-old
      Neolithic sites".
AB  - On the basis of analysis of ancient DNA from early European farmers, Haak et al.
      (Reports, 11 November 2005, p. 1016) argued for the Paleolithic ancestry of
      modern Europeans. We stress that the study is more limited in scope than the
      authors claim, in part because not all of the skeletal samples date to the time
      of the Neolithic transition in a given area of Europe.

PMID- 16809514
TI  - Community collaborations. Collaborative ecological restoration.

PMID- 16809516
TI  - Materials science. Seeking room-temperature ferromagnetic semiconductors.

PMID- 16809515
TI  - Cell signaling. H2O2, a necessary evil for cell signaling.

PMID- 16809517
TI  - Chemistry. Targeting specific C-H bonds for oxidation.

PMID- 16809518
TI  - Molecular biology. Accurate RNA siting and splicing gets help from a DEK-hand.

PMID- 16809519
TI  - Applied physics. The neutron spin-echo technique at full strength.

PMID- 16809520
TI  - Ecology. Climate change and crop yields: beyond Cassandra.

PMID- 16809522
TI  - The baby deficit.

PMID- 16809523
TI  - The bomb that wasn't.

PMID- 16809524
TI  - Some frontiers in social science.
AB  - The fundamental challenge in the social sciences is moving from complicated
      correlations to useful prediction. Progress usually reflects an interplay between
      theory, data, and tools. Six areas of innovation, principally data and tools, are
      now pushing at the frontiers of these sciences: longitudinal data, laboratory
      experimentation, improved statistical methods, geographic information tools,
      biosocial science, and international replication. These innovations are gaining
      power as they cross disciplinary boundaries, helping to attribute causality to
      observed relationships, to understand their nature, and thereby to improve the
      accuracy and usefulness of predictions.

PMID- 16809525
TI  - Skill formation and the economics of investing in disadvantaged children.
AB  - This paper summarizes evidence on the effects of early environments on child,
      adolescent, and adult achievement. Life cycle skill formation is a dynamic
      process in which early inputs strongly affect the productivity of later inputs.

PMID- 16809527
TI  - Politics and the life cycle.
AB  - The study of politics and the life cycle began with a rather single-minded focus
      on childhood and the family-on the idea, as Tocqueville famously put it, that the
      entire person could be "seen in the cradle of the child." Politics does begin in
      childhood, and parents do influence their offspring, but change takes place over
      the entire span of life. I take up the early emergence of partisanship and
      essentialism, the formation of generations, politically consequential transitions
      in adulthood, and the rising of politics and its final decline.

PMID- 16809526
TI  - Studying adolescence.
AB  - Young people in their teens constitute the largest age group in the world, in a
      special stage recognized across the globe as the link in the life cycle between
      childhood and adulthood. Longitudinal studies in both developed and developing
      countries and better measurements of adolescent behavior are producing new
      insights. The physical and psychosocial changes that occur during puberty make
      manifest generational and early-childhood risks to development, in the form of
      individual differences in aspects such as growth, educational attainment, self
      esteem, peer influences, and closeness to family. They also anticipate threats to
      adult health and well-being. Multidisciplinary approaches, especially links
      between the biological and the social sciences, as well as studies of
      socioeconomic and cultural diversity and determinants of positive outcomes, are
      needed to advance knowledge about this stage of development.

PMID- 16809528
TI  - Would you be happier if you were richer? A focusing illusion.
AB  - The belief that high income is associated with good mood is widespread but mostly
      illusory. People with above-average income are relatively satisfied with their
      lives but are barely happier than others in moment-to-moment experience, tend to
      be more tense, and do not spend more time in particularly enjoyable activities.
      Moreover, the effect of income on life satisfaction seems to be transient. We
      argue that people exaggerate the contribution of income to happiness because they
      focus, in part, on conventional achievements when evaluating their life or the
      lives of others.

PMID- 16809529
TI  - Redistributing work in aging Europe.
AB  - As Europe ages, the proportion of people who work will decline unless older
      individuals remain in the labor force. Such reform could be part of a more
      general redistribution of work. If a greater share of the population worked, then
      the average number of hours worked per week could be reduced. This could
      particularly help younger people and increase Europe's low birth rates. The
      challenges facing Germany, Europe's most populous country, are highlighted, but
      statistics are also given for five other European countries and, for comparison,
      the United States. Social science research is needed to provide policy-relevant
      knowledge about life-course options.

PMID- 16809530
TI  - The influence of a sense of time on human development.
AB  - The subjective sense of future time plays an essential role in human motivation.
      Gradually, time left becomes a better predictor than chronological age for a
      range of cognitive, emotional, and motivational variables. Socioemotional
      selectivity theory maintains that constraints on time horizons shift motivational
      priorities in such a way that the regulation of emotional states becomes more
      important than other types of goals. This motivational shift occurs with age but
      also appears in other contexts (for example, geographical relocations, illnesses,
      and war) that limit subjective future time.

PMID- 16809533
TI  - Frictional afterslip following the 2005 Nias-Simeulue earthquake, Sumatra.
AB  - Continuously recording Global Positioning System stations near the 28 March 2005
      rupture of the Sunda megathrust [moment magnitude (Mw) 8.7] show that the
      earthquake triggered aseismic frictional afterslip on the subduction megathrust,
      with a major fraction of this slip in the up-dip direction from the main rupture.
      Eleven months after the main shock, afterslip continues at rates several times
      the average interseismic rate, resulting in deformation equivalent to at least a
      M(w) 8.2 earthquake. In general, along-strike variations in frictional behavior
      appear to persist over multiple earthquake cycles. Aftershocks cluster along the
      boundary between the region of coseismic slip and the up-dip creeping zone. We
      observe that the cumulative number of aftershocks increases linearly with
      postseismic displacements; this finding suggests that the temporal evolution of
      aftershocks is governed by afterslip.

PMID- 16809532
TI  - Food for thought: lower-than-expected crop yield stimulation with rising CO2
      concentrations.
AB  - Model projections suggest that although increased temperature and decreased soil
      moisture will act to reduce global crop yields by 2050, the direct fertilization
      effect of rising carbon dioxide concentration ([CO2]) will offset these losses.
      The CO2 fertilization factors used in models to project future yields were
      derived from enclosure studies conducted approximately 20 years ago. Free-air
      concentration enrichment (FACE) technology has now facilitated large-scale trials
      of the major grain crops at elevated [CO2] under fully open-air field conditions.
      In those trials, elevated [CO2] enhanced yield by approximately 50% less than in
      enclosure studies. This casts serious doubt on projections that rising [CO2] will
      fully offset losses due to climate change.

PMID- 16809534
TI  - Spin-wave lifetimes throughout the Brillouin zone.
AB  - We used a neutron spin-echo method with microelectron-volt resolution to
      determine the lifetimes of spin waves in the prototypical antiferromagnet MnF2
      over the entire Brillouin zone. A theory based on the interaction of spin waves
      (magnons) with longitudinal spin fluctuations provides an excellent, parameter
      free description of the data, except at the lowest momenta and temperatures. This
      is surprising, given the prominence of alternative theories based on magnon
      magnon interactions in the literature. The results and technique open up a new
      avenue for the investigation of fundamental concepts in magnetism. The technique
      also allows measurement of the lifetimes of other elementary excitations, such as
      lattice vibrations, throughout the Brillouin zone.

PMID- 16809531
TI  - Bacterial diversity in tree canopies of the Atlantic forest.
AB  - We found an extraordinary level of bacterial biodiversity in the tree leaf canopy
      of a tropical Atlantic forest by using culture-independent molecular methods. Our
      survey suggests that each tree species selects for a distinct microbial
      community. Analysis of the bacterial 16S ribosomal RNA gene sequences revealed
      that about 97% of the bacteria were unknown species and that the phyllosphere of
      any one tree species carries at least 95 to 671 bacterial species. The tree
      canopies of tropical forests likely represent a large reservoir of unexplored
      microbial diversity.

PMID- 16809535
TI  - Surface and deep ocean interactions during the cold climate event 8200 years ago.
AB  - Evidence from a North Atlantic deep-sea sediment core reveals that the largest
      climatic perturbation in our present interglacial, the 8200-year event, is marked
      by two distinct cooling events in the subpolar North Atlantic at 8490 and 8290
      years ago. An associated reduction in deep flow speed provides evidence of a
      significant change to a major downwelling limb of the Atlantic meridional
      overturning circulation. The existence of a distinct surface freshening signal
      during these events strongly suggests that the sequenced surface and deep ocean
      changes were forced by pulsed meltwater outbursts from a multistep final drainage
      of the proglacial lakes associated with the decaying Laurentide Ice Sheet margin.

PMID- 16809536
TI  - Phase modifiers promote efficient production of hydroxymethylfurfural from
      fructose.
AB  - Furan derivatives obtained from renewable biomass resources have the potential to
      serve as substitutes for the petroleum-based building blocks that are currently
      used in the production of plastics and fine chemicals. We developed a process for
      the selective dehydration of fructose to 5-hydroxymethylfurfural (HMF) that
      operates at high fructose concentrations (10 to 50 weight %), achieves high
      yields (80% HMF selectivity at 90% fructose conversion), and delivers HMF in a
      separation-friendly solvent. In a two-phase reactor system, fructose is
      dehydrated in the aqueous phase with the use of an acid catalyst (hydrochloric
      acid or an acidic ion-exchange resin) with dimethylsulfoxide and/or poly(1-vinyl
      2-pyrrolidinone) added to suppress undesired side reactions. The HMF product is
      continuously extracted into an organic phase (methylisobutylketone) modified with
      2-butanol to enhance partitioning from the reactive aqueous solution.

PMID- 16809537
TI  - Molecular recognition in the selective oxygenation of saturated C-H bonds by a
      dimanganese catalyst.
AB  - Although enzymes often incorporate molecular recognition elements to orient
      substrates selectively, such strategies are rarely achieved by synthetic
      catalysts. We combined molecular recognition through hydrogen bonding with C-H
      activation to obtain high-turnover catalytic regioselective functionalization of
      sp3 C-H bonds remote from the -COOH recognition group. The catalyst contains a
      Mn(mu-O)2Mn reactive center and a ligand based on Kemp's triacid that directs a 
      COOH group to anchor the carboxylic acid group of the substrate and thus modify
      the usual selectivity for oxidation. Control experiments supported the role of
      hydrogen bonding in orienting the substrate to achieve high selectivity.

PMID- 16809538
TI  - The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.
AB  - Mathematical models predict that the future of the multidrug-resistant
      tuberculosis epidemic will depend on the fitness cost of drug resistance. We show
      that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin
      resistance is universally associated with a competitive fitness cost and that
      this cost is determined by the specific resistance mutation and strain genetic
      background. In contrast, we demonstrate that prolonged patient treatment can
      result in multidrug-resistant strains with no fitness defect and that strains
      with low- or no-cost resistance mutations are also the most frequent among
      clinical isolates.

PMID- 16809539
TI  - Lhx2 maintains stem cell character in hair follicles.
AB  - During embryogenesis, stem cells are set aside to fuel the postnatal hair cycle
      and repair the epidermis after injury. To define how hair follicle stem cells are
      specified and maintained in an undifferentiated state, we developed a strategy to
      isolate and transcriptionally profile embryonic hair progenitors in mice. We
      identified Lhx2 as a transcription factor positioned downstream of signals
      necessary to specify hair follicle stem cells, but upstream from signals required
      to drive activated stem cells to terminally differentiate. Using gain- and loss
      of-function studies, we uncovered a role for Lhx2 in maintaining the growth and
      undifferentiated properties of hair follicle progenitors.

PMID- 16809540
TI  - Structural basis of RNA-dependent recruitment of glutamine to the genetic code.
AB  - Glutaminyl-transfer RNA (Gln-tRNA(Gln)) in archaea is synthesized in a
      pretranslational amidation of misacylated Glu-tRNA(Gln) by the heterodimeric Glu
      tRNA(Gln) amidotransferase GatDE. Here we report the crystal structure of the
      Methanothermobacter thermautotrophicus GatDE complexed to tRNA(Gln) at 3.15
      angstroms resolution. Biochemical analysis of GatDE and of tRNA(Gln) mutants
      characterized the catalytic centers for the enzyme's three reactions
      (glutaminase, kinase, and amidotransferase activity). A 40 angstrom-long channel
      for ammonia transport connects the active sites in GatD and GatE. tRNA(Gln)
      recognition by indirect readout based on shape complementarity of the D loop
      suggests an early anticodon-independent RNA-based mechanism for adding glutamine
      to the genetic code.

PMID- 16809541
TI  - Ammonia channel couples glutaminase with transamidase reactions in GatCAB.
AB  - The formation of glutaminyl transfer RNA (Gln-tRNA(Gln)) differs among the three
      domains of life. Most bacteria employ an indirect pathway to produce Gln
      tRNA(Gln) by a heterotrimeric glutamine amidotransferase CAB (GatCAB) that acts
      on the misacylated Glu-tRNA(Gln). Here, we describe a series of crystal
      structures of intact GatCAB from Staphylococcus aureus in the apo form and in the
      complexes with glutamine, asparagine, Mn2+, and adenosine triphosphate analog.
      Two identified catalytic centers for the glutaminase and transamidase reactions
      are markedly distant but connected by a hydrophilic ammonia channel 30 A in
      length. Further, we show that the first U-A base pair in the acceptor stem and
      the D loop of tRNA(Gln) serve as identity elements essential for discrimination
      by GatCAB and propose a complete model for the overall concerted reactions to
      synthesize Gln-tRNA(Gln).

PMID- 16809542
TI  - Rapid advance of spring arrival dates in long-distance migratory birds.
AB  - Several bird species have advanced the timing of their spring migration in
      response to recent climate change. European short-distance migrants, wintering in
      temperate areas, have been assumed to be more affected by change in the European
      climate than long-distance migrants wintering in the tropics. However, we show
      that long-distance migrants have advanced their spring arrival in Scandinavia
      more than short-distance migrants. By analyzing a long-term data set from
      southern Italy, we show that long-distance migrants also pass through the
      Mediterranean region earlier. We argue that this may reflect a climate-driven
      evolutionary change in the timing of spring migration.

PMID- 16809543
TI  - Intron removal requires proofreading of U2AF/3' splice site recognition by DEK.
AB  - Discrimination between splice sites and similar, nonsplice sequences is essential
      for correct intron removal and messenger RNA formation in eukaryotes. The 65- and
      35-kD subunits of the splicing factor U2AF, U2AF65 and U2AF35, recognize,
      respectively, the pyrimidine-rich tract and the conserved terminal AG present at
      metazoan 3' splice sites. We report that DEK, a chromatin- and RNA-associated
      protein mutated or overexpressed in certain cancers, enforces 3' splice site
      discrimination by U2AF. DEK phosphorylated at serines 19 and 32 associates with
      U2AF35, facilitates the U2AF35-AG interaction and prevents binding of U2AF65 to
      pyrimidine tracts not followed by AG. DEK and its phosphorylation are required
      for intron removal, but not for splicing complex assembly, which indicates that
      proofreading of early 3' splice site recognition influences catalytic activation
      of the spliceosome.

PMID- 16809544
TI  - The ant odometer: stepping on stilts and stumps.
AB  - Desert ants, Cataglyphis, navigate in their vast desert habitat by path
      integration. They continuously integrate directions steered (as determined by
      their celestial compass) and distances traveled, gauged by as-yet-unknown
      mechanisms. Here we test the hypothesis that navigating ants measure distances
      traveled by using some kind of step integrator, or "step counter." We manipulated
      the lengths of the legs and, hence, the stride lengths, in freely walking ants.
      Animals with elongated ("stilts") or shortened legs ("stumps") take larger or
      shorter strides, respectively, and concomitantly misgauge travel distance. Travel
      distance is overestimated by experimental animals walking on stilts and
      underestimated by animals walking on stumps.

PMID- 16809545
TI  - Social modulation of pain as evidence for empathy in mice.
AB  - Empathy is thought to be unique to higher primates, possibly to humans alone. We
      report the modulation of pain sensitivity in mice produced solely by exposure to
      their cagemates, but not to strangers, in pain. Mice tested in dyads and given an
      identical noxious stimulus displayed increased pain behaviors with statistically
      greater co-occurrence, effects dependent on visual observation. When familiar
      mice were given noxious stimuli of different intensities, their pain behavior was
      influenced by their neighbor's status bidirectionally. Finally, observation of a
      cagemate in pain altered pain sensitivity of an entirely different modality,
      suggesting that nociceptive mechanisms in general are sensitized.

PMID- 16809546
TI  - Adrenomedullin/cyclic AMP pathway induces Notch activation and differentiation of
      arterial endothelial cells from vascular progenitors.
AB  - OBJECTIVE: The acquisition of arterial or venous identity is highlighted in
      vascular development. Previously, we have reported an embryonic stem (ES) cell
      differentiation system that exhibits early vascular development using vascular
      endothelial growth factor (VEGF) receptor-2 (VEGFR2)-positive cells as common
      vascular progenitors. In this study, we constructively induced differentiation of
      arterial and venous endothelial cells (ECs) in vitro to elucidate molecular
      mechanisms of arterial-venous specification. METHODS AND RESULTS: ECs were
      induced from VEGFR2+ progenitor cells with various conditions. VEGF was essential
      to induce ECs. Addition of 8bromo-cAMP or adrenomedullin (AM), an endogenous
      ligand-elevating cAMP, enhanced VEGF-induced EC differentiation. Whereas VEGF
      alone mainly induced venous ECs, 8bromo-cAMP (or AM) with VEGF supported
      substantial induction of arterial ECs. Stimulation of cAMP pathway induced Notch
      signal activation in ECs. The arterializing effect of VEGF and cAMP was abolished
      in recombination recognition sequence binding protein at the Jkappa site
      deficient ES cells lacking Notch signal activation or in ES cells treated with
      gamma-secretase inhibitor. Nevertheless, forced Notch activation by the
      constitutively active Notch1 alone did not induce arterial ECs. CONCLUSIONS:
      Adrenomedullin/cAMP is a novel signaling pathway to activate Notch signaling in
      differentiating ECs. Coordinated signaling of VEGF, Notch, and cAMP is required
      to induce arterial ECs from vascular progenitors.

PMID- 16809547
TI  - CX3CR1 deficiency confers protection from intimal hyperplasia after arterial
      injury.
AB  - OBJECTIVE: A functional polymorphism in the chemokine receptor CX3CR1 is
      associated with protection from vascular diseases including coronary artery
      disease and internal carotid artery occlusive disease. We investigated the
      mechanisms by which CX3CR1 may be involved by evaluating the inflammatory
      response to arterial injury in CX3CR1-deficient animals. METHODS AND RESULTS:
      Femoral arteries of CX3CR1-/- and wild-type (WT) mice were injured with an
      angioplasty guide wire. After 1, 5, 14, and 28 days, arteries were harvested and
      evaluated by histology, morphometry, and immunohistochemistry. Arterial injury
      upregulated the CX3CR1 ligand CX3CL1. In CX3CR1-/- compared with WT animals, the
      incidence of neointima formation was 58% lower (P=0.0017), accompanied by no
      difference in the area of platelet accumulation at day 1 (P=0.48) but a
      significant decrease in intimal monocyte infiltration at day 5 (P=0.006),
      vascular smooth muscle cell (VSMC) proliferation at days 5 and 14, and intimal
      area at day 28 (P=0.009). CONCLUSIONS: In an endothelial denudation injury model,
      CX3CR1 deficiency protects animals from developing intimal hyperplasia as a
      result of decreased monocyte trafficking to the lesion. CX3CR1 deficiency
      decreases VSMC proliferation and intimal accumulation either directly or
      indirectly as a result of defective monocyte infiltration.

PMID- 16809548
TI  - Abdominal aortic aneurysm rupture is associated with increased medial
      neovascularization and overexpression of proangiogenic cytokines.
AB  - OBJECTIVE: Matrix metalloproteinase (MMP) activity has been linked to abdominal
      aortic aneurysm (AAA) rupture. Medial neovascularization (MNV), a histopathologic
      characteristic of AAAs, involves proteolytic degradation of extracellular matrix
      by MMPs to facilitate endothelial cell migration. The role of MNV in aneurysm
      rupture is unknown. This study investigated whether MNV is increased in aneurysm
      rupture. METHODS AND RESULTS: Biopsy samples from aneurysm rupture edge were
      compared with control biopsy samples from aneurysm wall at the level of rupture
      and from anterior sac in 12 ruptured AAAs. Further controls were obtained from
      anterior sac of 10 nonruptured AAAs. MNV, microvessel diameter, maturity index,
      and inflammatory infiltrate were quantified using morphometric analyses following
      immunohistochemistry. Expression of proangiogenic mediators was quantified using
      quantitative real-time-polymerase chain reaction. Compared with anterior sac and
      aneurysm wall at level of rupture, MNV was increased (P<0.001) in rupture edge
      biopsy samples and consisted of smaller diameter (P<0.001) and more immature
      microvessels (P<0.001). mRNA expression of alpha(v)-integrin, vascular
      endothelial growth factor, vascular endothelial-cadherin, monocyte
      chemoattractant protein-1, and vimentin was increased (P<0.05) in rupture edge
      biopsy samples. CONCLUSIONS: This study demonstrated increased medial
      neovascularization and overexpression of proangiogenic cytokines at aneurysm
      rupture edge. Further investigations into whether this angiogenic response was a
      causative factor of aneurysm rupture are needed.

PMID- 16809549
TI  - Fibroblast growth factor-2 failed to induce angiogenesis in junctional adhesion
      molecule-A-deficient mice.
AB  - OBJECTIVE: We have previously shown that JAM-A regulates fibroblast growth factor
      2 (FGF-2)-induced endothelial cell morphology, proliferation, and migration.
      Whether JAM-A is involved in FGF-2-induced angiogenesis in vivo is not known. We
      used JAM-A null mice to conclusively determine the role of JAM-A in FGF-2-induced
      neovascularization. METHODS AND RESULTS: We generated JAM-A null (JAM-A(-/-))
      mice using gene trap technology. These mice, although viable and fertile,
      exhibited distorted Mendelian and sex ratios, suggesting partial embryonic
      lethality. Retinal fluorescein angiogram did not reveal any significant
      morphological differences in the vasculature of JAM-A(-/-) mice compared with
      wild-type (JAMA-A(+/+)) littermates. To evaluate the role of JAM-A in
      angiogenesis, we performed an aortic ring assay. FGF-2-induced microvessel growth
      was evident in aortic rings from JAM-A(+/+) mice, but FGF-2 failed to induce
      microvessel sproutings in aortic rings from JAM-A(-/-) mice. In a Matrigel plug
      assay, a known in vivo model for angiogenesis, we found that FGF-2 induced a
      robust vessel growth in JAM-A(+/+) mice, whereas FGF-2 failed to induce blood
      vessel formation in plugs from JAM-A(-/-) mice. CONCLUSIONS: Our results using
      JAM-A(-/-) mice presented here conclusively establish an essential role for JAM-A
      in FGF-2-induced angiogenesis.

PMID- 16809550
TI  - Endocytosis of extracellular superoxide dismutase into endothelial cells: role of
      the heparin-binding domain.
AB  - OBJECTIVE: Extracellular superoxide dismutase (EC-SOD) is a secreted antioxidant
      enzyme that binds to the outer plasma membrane and extracellular matrix through
      its heparin-binding domain (HBD). Carriers of a common genetic variant of EC-SOD
      (EC-SOD(R213G), within the HBD) have higher plasma concentration of EC-SOD and
      increased risk for vascular disease. In the present study, we used confocal
      fluorescence microscopy to examine mechanisms of endocytosis of EC-SOD to
      determine whether EC-SOD translocates to the nucleus of endothelial cells, and to
      test the hypothesis that EC-SOD, but not EC-SOD(R213G), is endocytosed into
      endothelial cells. METHODS AND RESULTS: Mouse endothelial cells (MS-1) were
      incubated with EC-SOD, EC-SOD(R213G), or HBD-deleted EC-SOD (EC-SODdeltaHBD).
      Binding to MS-1 was observed only with EC-SOD, but not EC-SOD(R213G) or EC
      SODdeltaHBD. Endocytosis of EC-SODs was monitored after coincubation of MS-1
      cells with EC-SODs and BSA-Texas Red (BSA-TR), which marks endosomes and
      lysosomes. Only EC-SOD was endocytosed, colocalizing with BSA-TR. EC-SOD also
      colocalized with early endosome antigen 1 (EEA-1), a specific marker for
      endocytosis. Endocytosis of EC-SOD was inhibited by chlorpromazine, but not by
      methyl-beta-cyclodextrin or nystatin, which suggests that endocytosis of EC-SOD
      is mediated by clathrin but not by caveolae. Minimal or no localization of EC-SOD
      in the nucleus of MS-1 cells was detected. CONCLUSIONS: Our findings indicate
      that EC-SOD, but not EC-SOD(R213G), is endocytosed into endothelial cells through
      clathrin-mediated pathway, but does not translocate to the nucleus. We speculate
      that impairment of endocytosis may contribute to high plasma levels of EC
      SOD(R213G) in R213G carriers.

PMID- 16809551
TI  - Cardiac myosin light chain-2: a novel essential component of thick-myofilament
      assembly and contractility of the heart.
AB  - Although it is well known that mutations in the cardiac regulatory myosin light
      chain-2 (mlc-2) gene cause hypertrophic cardiomyopathy, the precise in vivo
      structural and functional roles of MLC-2 in the heart are only poorly understood.
      We have isolated a mutation in zebrafish, tell tale heart (tel(m225)), which
      selectively perturbs contractility of the embryonic heart. By positional cloning,
      we identified tel to encode the zebrafish mlc-2 gene. In contrast to mammals,
      zebrafish have only 1 cardiac-specific mlc-2 gene, which we find to be expressed
      in atrial and ventricular cardiomyocytes during early embryonic development, but
      also in the adult heart. Accordingly, loss of zMLC-2 function cannot be
      compensated for by upregulation of another mlc-2 gene. Surprisingly,
      ultrastructural analysis of tel cardiomyocytes reveals complete absence of
      organized thick myofilaments. Thus, our findings provide the first in vivo
      evidence that cardiac MLC-2 is required for thick-filament stabilization and
      contractility in the vertebrate heart.

PMID- 16809553
TI  - The value of quality of life research in stroke.

PMID- 16809552
TI  - PICOT inhibits cardiac hypertrophy and enhances ventricular function and
      cardiomyocyte contractility.
AB  - Multiple signaling pathways involving protein kinase C (PKC) have been implicated
      in the development of cardiac hypertrophy. We observed that a putative PKC
      inhibitor, PICOT (PKC-Interacting Cousin Of Thioredoxin) was upregulated in
      response to hypertrophic stimuli both in vitro and in vivo. This suggested that
      PICOT may act as an endogenous negative feedback regulator of cardiac hypertrophy
      through its ability to inhibit PKC activity, which is elevated during cardiac
      hypertrophy. Adenovirus-mediated gene transfer of PICOT completely blocked the
      hypertrophic response of neonatal rat cardiomyocytes to enthothelin-1 and
      phenylephrine, as demonstrated by cell size, sarcomere rearrangement, atrial
      natriuretic factor expression, and rates of protein synthesis. Transgenic mice
      with cardiac-specific overexpression of PICOT showed that PICOT is a potent
      inhibitor of cardiac hypertrophy induced by pressure overload. In addition, PICOT
      overexpression dramatically increased the ventricular function and cardiomyocyte
      contractility as measured by ejection fraction and end-systolic pressure of
      transgenic hearts and peak shortening of isolated cardiomyocytes, respectively.
      Intracellular Ca(2+) handing analysis revealed that increases in myofilament
      Ca(2+) responsiveness, together with increased rate of sarcoplasmic reticulum
      Ca(2+) reuptake, are associated with the enhanced contractility in PICOT
      overexpressing cardiomyocytes. The inhibition of cardiac remodeling by of PICOT
      with a concomitant increase in ventricular function and cardiomyocyte
      contractility suggests that PICOT may provide an efficient modality for treatment
      of cardiac hypertrophy and heart failure.

PMID- 16809554
TI  - Temporal profiles of axon terminals, synapses and spines in the ischemic penumbra
      of the cerebral cortex: ultrastructure of neuronal remodeling.
AB  - BACKGROUND AND PURPOSE: Because the recovery process of axon terminals, synapses,
      and spine-dendrites in the ischemic penumbra of the cerebral cortex is obscure,
      we studied the temporal profile of these structures up to 12 weeks after the
      ischemic insult, using a gerbil model. METHODS: Stroke-positive animals were
      selected according to their stroke index score during the first 10-minute left
      carotid occlusion done twice with 5-hour interval. The animals were euthanized at
      various times after the second ischemic insult. Ultra-thin sections including the
      2nd to 4th cortical layers were obtained from the neocortex coronally sectioned
      at the infundibular level, in which the penumbra appeared. We counted the number
      of synapses, spines and multiple synapse boutons, measured neurite thickness, and
      determined the percent volume of the axon terminals and spines by Weibel point
      counting method. RESULTS: The number of synapses, synaptic vesicles and spines
      and the total percent volume of the axon terminals and spines decreased until the
      4th day. From 1 to 12 weeks after the ischemic insult, these values increased to
      or exceeded the control ones, and neuritic thickening and increase in number of
      multiple synapse boutons occurred. CONCLUSIONS: In the ischemic penumbra, the
      above structures degenerated, with a reduction in their number and size, until 4
      days and then recovered from 1 to 12 weeks after the ischemic insult.

PMID- 16809555
TI  - Serum C-reactive protein concentration and genotype in relation to ischemic
      stroke subtype.
AB  - BACKGROUND AND PURPOSE: C-reactive protein (CRP) has evolved as an inflammatory
      risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at
      the CRP locus have been found to be associated with CRP levels. The aim of the
      present study was to investigate CRP levels and genetic variants in etiological
      subtypes of ischemic stroke. METHODS: The Sahlgrenska Academy Study on Ischemic
      Stroke (SAHLSIS) comprises 600 consecutive ischemic stroke cases (18 to 69 years)
      and 600 matched controls from western Sweden. Stroke subtypes were defined by the
      TOAST classification. Serum CRP levels were determined by a high-sensitivity
      immunometric assay. RESULTS: CRP levels were significantly higher for all
      ischemic stroke subtypes compared with controls, both in the acute phase and at
      the 3-month follow-up. After adjustment for traditional risk factors, CRP at
      follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR,
      1.25; 95% CI, 1.09 to 1.43) and large-vessel disease (OR, 1.48; 95% CI, 1.09 to
      2.00). The CRP -286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms
      showed significant associations with CRP levels. However, neither CRP genotypes
      nor haplotypes showed an association to overall ischemic stroke. CONCLUSIONS:
      This is the first large study on CRP in different TOAST subtypes in a young
      ischemic stroke population. CRP levels differed between etiological subtypes of
      ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at
      follow-up was associated with overall ischemic stroke and the large-vessel
      disease subtype. Genetic variants at the CRP locus were associated with CRP
      levels, but no association was detected for overall ischemic stroke.

PMID- 16809556
TI  - Pretreatment with antiplatelet agents is not independently associated with
      unfavorable outcome in intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: This study investigated the effect of preexisting
      antiplatelet therapy on mortality and functional outcome in patients with
      intracerebral hemorrhage (ICH). METHODS: Our analysis was based on a large,
      country-wide stroke registry in Germany. All parameters relevant to this
      analysis, including age, prehospital status (according to the modified Rankin
      Scale, mRS), International Classification of Diseases-based diagnosis, and
      pretreatment with antiplatelet agents or oral anticoagulants, were recorded
      prospectively. Main outcome measures were in-hospital mortality rate and
      functional status at hospital discharge (mRS). RESULTS: Over a 2-year period,
      1691 patients with ICH (ICD-10: I61) were documented (48% female; mean age, 72+/
      12 years). At symptom onset, 26% were taking antiplatelet agents, and 12% were
      taking oral anticoagulants. By univariate logistic regression, pretreatment with
      antiplatelet drugs or anticoagulants was found to be a significant predictor of
      in-hospital mortality (odds ratio [OR], 1.42; P=0.008; OR, 1.53; P<0.001) and of
      an unfavorable functional outcome (defined as mRS >2 or death; OR, 1.33, P=0.039;
      OR, 1.51; P<0.001). However, after adjustment for age and prehospital status,
      antiplatelet pretreatment was no longer an independent risk factor of in-hospital
      death (OR, 1.12; P=0.490) or unfavorable functional outcome (OR, 0.97; P=0.830),
      whereas the influence of pretreatment with oral anticoagulants remained
      significant (OR, 1.45; P<0.001; OR, 1.42; P=0.009). CONCLUSIONS: In contrast to
      oral anticoagulants, pretreatment with antiplatelet agents is not an independent
      risk factor of mortality and unfavorable outcome in patients with ICH.

PMID- 16809557
TI  - Safety and effectiveness of radioactive coil embolization of aneurysms: effects
      of radiation on recanalization, clot organization, neointima formation, and
      surrounding nerves in experimental models.
AB  - BACKGROUND AND PURPOSE: Recanalization after coil embolization can be prevented
      by radiation emitted from 32P coils. We wanted to determine the upper limits of
      32P activities that could be implanted onto coils with respect to the potential
      injury to nearby nerves, delay in organization of the clot, and effects on
      neointima formation and recanalization. METHODS: We studied the effects of
      various 32P activities on recanalization and organization of thrombus after coil
      occlusion of canine arteries and on neointima formation at the neck of canine
      carotid bifurcation aneurysms. We also tested potential injury to nerves in the
      vicinity of radioactive or nonradioactive coils in 3 models: the brachial plexus
      (near proximal vertebral arteries) and the lingual nerve in a lingual artery
      bifurcation aneurysm model, both models being treated by radioactive or standard
      coil occlusion. Finally, we wrapped lingual nerves with nonradioactive or high
      activity coils and studied their effects on lingual nerves and tongues. Results
      were assessed with a pathological scoring system and compared with Mann-Whitney
      and Kruskal-Wallis tests. RESULTS: No deleterious effect of radiation on nerves
      could be detected. Neointima formation was not hampered, scores of aneurysms
      treated with 32P-coils being significantly better when compared with treatments
      with standard coils (P=0.002). Arteries treated with high-activity coils (>3.39
      microCi) showed absent recanalization but delayed organization of the clot at 3
      months compared with low-activity or nonradioactive coils (P<0.05). CONCLUSIONS:
      beta-Radiation can prevent recanalization after coil occlusion. We could not
      demonstrate any deleterious effects of radioactivity on nervous structure or on
      neointima formation. Delayed organization of thrombus provides a rational basis
      to establish an upper limit for 32P activities to be implanted onto coils.

PMID- 16809559
TI  - Statin treatment is not associated with consistent alterations in inflammatory
      status of carotid atherosclerotic plaques: a retrospective study in 378 patients
      undergoing carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Anti-inflammatory qualities are held partially
      responsible for the reduction of cardiovascular events after statin treatment. We
      examined the phenotype of carotid atherosclerotic plaques harvested during
      carotid endarterectomy in relation to the previous use of different statins
      prescribed in clinical practice. METHODS: Three hundred and seventy-eight
      patients were included. Atherosclerotic plaques were harvested,
      immunohistochemically stained and semiquantitively examined for the presence of
      macrophages (CD68), smooth muscle cells, collagen and fat. Adjacent
      atherosclerotic plaques were used to study protease activity and interleukin
      levels. Patients' demographics were recorded and blood samples were stored.
      RESULTS: Serum cholesterol, low-density lipoprotein, apolipoprotein B, and C
      reactive protein levels were lower in patients treated with statins compared with
      patients without statin treatment. Atheromatous plaques were less prevalent in
      patients receiving statins compared with patients without statin therapy (29%
      versus 42%, P=0.04). An increase of CD68 positive cells was observed in patients
      receiving statins compared with nonstatin treatment (P=0.05). This effect was
      specifically related to atorvastatin treatment. In patients treated with
      atorvastatin, the increased amount of CD68 positive cells were not associated
      with increased protease activity. In contrast, a dose-dependent decrease in
      protease activity was shown in the atorvastatin group. Interleukin 6 expression
      was lower in plaques obtained from patients treated with statins (P=0.04).
      CONCLUSIONS: Statin use may exert pleiotropic effects on plaque phenotype.
      However, not the presence of macrophages but activation with subsequent protease
      and cytokine release may be attenuated by statin use.

PMID- 16809560
TI  - Intra-arterial thrombolysis for acute ischemic stroke.

PMID- 16809561
TI  - Safety of oral anticoagulation in elderly atrial fibrillation patients to prevent
      strokes.

PMID- 16809562
TI  - Diffusion-weighted imaging in stroke attributable to patent foramen ovale:
      significance of concomitant atrial septum aneurysm.
AB  - BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) is an established cause of
      stroke in young patients without other determined etiologies (ie, cryptogenic
      stroke). The additional presence of atrial septum aneurysm (ASA) possibly
      increases stroke risk, but it remains undetermined which factors best predict
      thromboembolism in patients with PFO. Diffusion-weighted imaging (DWI) may help
      to distinguish the characteristics of cerebral embolism associated with different
      features of the interatrial septum in PFO stroke. METHODS: In a stroke databank
      based cohort study, DWI and transthoracic/transesophageal echocardiography
      findings were assessed in 48 consecutive patients with cryptogenic ischemic
      stroke associated with PFO. The number, size, and distribution of acute ischemic
      lesions on DWI were correlated with PFO size, degree of interatrial right-to-left
      shunt (RLS), and the presence of ASA. RESULTS: Patients with PFO plus ASA
      combined more often had multiple acute DWI lesions (16 of 30, 53%) than those
      with PFO alone (3 of 18, 17%; P=0.01). This association remained significant
      after correction for PFO size, degree of RLS, and vascular risk factors in a
      logistic-regression analysis (P=0.04). No significant associations between DWI
      lesion characteristics and PFO size or degree of RLS were found. CONCLUSIONS: The
      presence of concomitant ASA is independently associated with multiple cerebral
      ischemic lesions in PFO stroke, which may indicate an increased embolic risk.

PMID- 16809564
TI  - Complement C3 and C-reactive protein are elevated in South Asians independent of
      a family history of stroke.
AB  - BACKGROUND AND PURPOSE: Complement components are emerging risk factors for
      cardiovascular disease. In this study, we examined the relation among C3, C
      reactive protein (CRP), factor B, and features of the insulin resistance (IR)
      syndrome in 143 first-degree relatives of South Asian subjects with ischemic
      stroke, 141 South Asian controls, and 121 white controls. METHODS: C3, CRP (high
      sensitivity assay), and factor B levels were measured by ELISAs, and their
      relation to features of the IR syndrome were assessed. Data are presented as
      geometric mean (95% CI). RESULTS: There was no significant difference in the
      levels of C3 between South Asian relatives (1.25 [1.21, 1.29] g/L) and South
      Asian controls (1.20 [1.15, 1.24] g/L, P=0.2). Levels in both South Asian groups
      were significantly higher than in white controls (0.95 [0.92, 0.98] g/L; P<0.001
      for both comparisons). These differences remained significant after adjustment
      for covariates. Similarly, levels of CRP were not different between the 2 South
      Asian groups, but levels in both South Asian groups, after adjustment for
      covariates, were significantly higher than in white controls. There was no
      difference in the levels of factor B among the 3 groups. South Asian subjects
      with elevated C3 levels clustered risk factors associated with IR to a greater
      extent than those with high CRP. CONCLUSIONS: These results suggest that South
      Asians have a greater level of chronic subclinical inflammation than do whites,
      independent of a family history of stroke. In addition, C3 is more likely to
      cluster with features of the IR syndrome compared with CRP in South Asians.

PMID- 16809563
TI  - Impairment of dilator responses of cerebral arterioles during diabetes mellitus:
      role of inducible NO synthase.
AB  - BACKGROUND AND PURPOSE: During diabetes, expression of inducible nitric oxide
      synthase (iNOS) plays an important role in the development of endothelial
      dysfunction in extracranial blood vessels. Progression of vascular dysfunction
      after the onset of diabetes differs among vascular beds. In this study, the
      effects of hyperglycemia/diabetes on vasomotor function were examined in cerebral
      arterioles at 2 different times in control and iNOS-deficient mice and compared
      with the effects on carotid arteries. METHODS: Streptozotocin (150 mg/kg IP) was
      given to induce diabetes. The diameter of cerebral arterioles was measured
      through a cranial window in diabetic and nondiabetic mice in vivo. Vasomotor
      function of the carotid artery was examined in vitro. RESULTS: In diabetic mice,
      responses of the cerebral arterioles to acetylcholine (1 mumol/L) were normal
      after 3 weeks of diabetes but were significantly impaired after 5 to 6 weeks of
      diabetes (4+/-1% [mean+/-SEM] increase in diameter) compared with control mice
      (14+/-1; P=0.0002). Responses to sodium nitroprusside were similar in diabetic
      and nondiabetic mice at both time points. In contrast, the vasomotor function of
      the carotid artery was not affected after 5 to 6 weeks of diabetes. In diabetic
      iNOS-deficient mice, cerebral arteriolar vasomotor function was not impaired,
      even after 4 months of diabetes. CONCLUSIONS: During diabetes, endothelial
      dysfunction of cerebral arterioles requires expression of iNOS and develops
      earlier than in carotid arteries.

PMID- 16809565
TI  - An integrated automated analysis method for quantifying vessel stenosis and
      plaque burden from carotid MRI images: combined postprocessing of MRA and vessel
      wall MR.
AB  - BACKGROUND AND PURPOSE: We report the evaluation of a semiautomated method for in
      vivo assessment of the severity of carotid atherosclerosis with minimal user
      interaction that combines 3-dimensional contrast-enhanced magnetic resonance
      angiography (CE-MRA) and vessel wall magnetic resonance imaging (MRI). METHODS:
      Lumen and outer-wall contours were automatically detected, and stenosis and
      plaque burden were estimated. The method was tested on 22 subjects (352
      postcontrast, T1-weighted cross sections and 3-dimensional CE-MRA). RESULTS: We
      observed good correlation with expert contours: lumen and outer-wall area
      (r=0.96) and the degree of stenosis (r=0.97). CONCLUSIONS: The fusion of MRA and
      MRI reduces user interaction and improves contour detection, providing
      reproducible parameters to assess the severity of atherosclerosis.

PMID- 16809566
TI  - Recent evidence for an involvement of rho-kinase in cerebral vascular disease.
AB  - BACKGROUND AND PURPOSE: The small G protein rhoA and its downstream effector rho
      kinase are both expressed in vascular cells and are involved in several cellular
      processes. One of these processes is the regulation of the phosphorylation state
      of myosin light chain in vascular muscle and thus, the development of force.
      Recently, considerable evidence for increased activity of this pathway in
      cerebral and noncerebral vessels has been reported in several cardiovascular
      diseases associated with increased vascular tone. SUMMARY OF REVIEW: The main aim
      of this brief review is to summarize current evidence for the involvement of
      rhoA/rho-kinase signaling in dysfunction of the cerebral circulation in disease
      states, such as cerebral vasospasm, hypertension, diabetes, and ischemic brain
      injury. We will also briefly consider the novel hypothesis that augmented
      activity of endothelial rho-kinase decreases nitric oxide production and
      contributes to increased vascular tone in disease and the possibility of this
      action being a key therapeutic target of statins (inhibitors of 3-hydroxy-3
      methylglutaryl coenzyme A reductase) in cerebral and noncerebral arteries.
      CONCLUSIONS: Considerable evidence indicates that rhoA/rho-kinase activity is
      commonly increased in cerebral vascular disease, not only in vascular muscle, but
      also in the endothelium and possibly in inflammatory cells and neurons.

PMID- 16809567
TI  - Recurrent extracranial carotid artery vasospasms: report of 2 cases.
AB  - BACKGROUND AND PURPOSE: Spontaneous vasospasms of the submandibular internal
      carotid arteries are rarely observed. They are a highly dynamic process, recur
      frequently, and can be detected by serial ultrasound examinations. SUMMARY OF
      CASES: We present 2 cases of recurrent extracranial vasospasms of the internal
      carotid artery as a cause of stroke. In both cases, arterial dissection was
      initially suspected, but no intramural hematoma was detected on magnetic
      resonance imaging. Duplex sonography demonstrated recurrent high-grade stenoses
      of both internal carotid arteries that resolved spontaneously within hours to
      days. The vasospasms were treated with calcium antagonists and in 1 patient with
      oral corticoids. CONCLUSIONS: Extracranial vasospasms as a cause of stroke might
      be underestimated. Vasospasms of the internal carotid arteries should be
      considered in patients with recurring ischemic events in the absence of any other
      explanation. Antiphlogistic treatment in combination with calcium antagonists
      might be effective to reduce the frequency of vasospasms.

PMID- 16809568
TI  - ADMA increases arterial stiffness and decreases cerebral blood flow in humans.
AB  - BACKGROUND AND PURPOSE: Preclinical studies have revealed that the endogenous
      nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), increases
      vascular tone in cerebral blood vessels. Marked elevations of ADMA blood levels
      were found in patients with diseases characterized by decreased cerebral
      perfusion, such as ischemic stroke. Arterial stiffness is an independent
      predictor of stroke and other adverse cardiovascular events. The aim of this
      study was to investigate the influence of a systemic subpressor dose of ADMA on
      arterial stiffness and cerebral perfusion in humans. METHODS: Using a double
      blind, vehicle-controlled study design, we allocated 20 healthy men in random
      order to infusion of either ADMA (0.10 mg ADMA/kg per min) or vehicle over a
      period of 40 minutes. Arterial stiffness was assessed noninvasively by pulse wave
      analysis. All volunteers underwent measurement of cerebral perfusion by dynamic
      contrast-enhanced perfusion magnetic resonance imaging of the brain. RESULTS:
      Infusion of ADMA significantly decreased total cerebral perfusion by 15.1+/-4.5%
      (P=0.007), whereas blood flow in the vehicle group increased by 7.7+/-2.8%
      (P=0.02). ADMA also increased arterial stiffness as assessed by measurement of
      the augmentation index (-12.6+/-1.9 to -9.6+/-1.5, P=0.007). CONCLUSIONS: Our
      results document for the first time that subpressor doses of ADMA increase
      vascular stiffness and decrease cerebral perfusion in healthy subjects. Thus,
      ADMA is an important endogenous modulator of cerebral vascular tone and may be
      involved in the pathogenesis of cerebrovascular disease.

PMID- 16809569
TI  - A sham-controlled trial of a 5-day course of repetitive transcranial magnetic
      stimulation of the unaffected hemisphere in stroke patients.
AB  - BACKGROUND AND PURPOSE: It has been recently shown that a single session of
      repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere
      can improve motor function in stroke patients; however, this improvement is short
      lasting. We therefore conducted a randomized, sham-controlled, phase II trial to
      evaluate whether five sessions of low-frequency rTMS can increase the magnitude
      and duration of these effects and whether this approach is safe. METHODS: Fifteen
      patients with chronic stroke were randomized to receive active or sham rTMS of
      the unaffected hemisphere. A blinded rater assessed motor function and
      corticospinal excitability at baseline, during and after 2 weeks of treatment.
      Safety was assessed using a neuropsychologic battery and electroencephalogram.
      RESULTS: Active rTMS resulted in a significant improvement of the motor function
      performance in the affected hand that lasted for 2 weeks. These effects were not
      observed in the sham rTMS group (affected and unaffected hand) and in the
      unaffected hand in the active rTMS group. Corticospinal excitability decreased in
      the stimulated, unaffected hemisphere and increased in the affected hemisphere.
      There was a significant correlation between motor function improvement and
      corticospinal excitability change in the affected hemisphere. Cognitive
      performance and electroencephalogram were not changed significantly throughout
      the trial in both groups of treatment. CONCLUSIONS: These results support and
      extend the findings of previous studies on rTMS in stroke patients because five
      consecutive sessions of rTMS increased the magnitude and duration of the motor
      effects. Furthermore, this increased dose of rTMS is not associated with
      cognitive adverse effects and/or epileptogenic activity.

PMID- 16809570
TI  - The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for
      acute ischemic stroke--II: neurologic outcome and efficacy analysis.
AB  - BACKGROUND AND PURPOSE: High-dose human albumin (ALB) is robustly neuroprotective
      in rodent stroke models. A phase I dose-escalation study was conducted to assess
      the safety of ALB therapy in ischemic stroke. We analyzed the data for
      preliminary evidence of treatment efficacy. METHODS: Eighty-two subjects with
      acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received 25% ALB
      beginning within 16 hours of stroke onset. Six successive ALB dose tiers were
      assessed (range, 0.34 to 2.05 g/kg). Forty-two patients also received standard-of
      care intravenous tissue plasminogen activator (tPA). Efficacy outcomes were
      determined at 3 months. We compared the highest three, putatively therapeutic ALB
      dose tiers (1.37 to 2.05 g/kg) with the lowest three, presumed subtherapeutic
      doses (0.34 to 1.03 g/kg) and with historical cohort data derived from the NINDS
      rt-PA Stroke Study. RESULTS: After adjusting for the tPA effect, the probability
      of good outcome (defined as modified Rankin Scale 0 to 1 or NIH Stroke Scale 0 to
      1 at 3 months) at the highest three ALB doses was 81% greater than in the lower
      dose-tiers (relative risk [RR], 1.81; 95% confidence interval [CI], 1.11 to 2.94)
      and was 95% greater than in the comparable NINDS rt-PA Stroke Study cohort (RR,
      1.95; 95% CI, 1.47 to 2.57). The tPA-treated subjects who received higher-dose
      ALB were three times more likely to achieve a good outcome than subjects
      receiving lower-dose ALB, suggesting a positive synergistic effect between ALB
      and tPA. CONCLUSIONS: Our data suggest that high-dose ALB therapy may be
      neuroprotective after ischemic stroke. These results have led to a multicenter,
      randomized, placebo-controlled efficacy trial of ALB in acute ischemic stroke-the
      ALIAS Phase III Trial.

PMID- 16809571
TI  - The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for
      acute ischemic stroke--I: Physiological responses and safety results.
AB  - BACKGROUND AND PURPOSE: In preclinical stroke models, high-dose human albumin
      confers robust neuroprotection. We investigated the safety and tolerability of
      this therapy in patients with acute ischemic stroke. METHODS: The ALIAS (Albumin
      in Acute Stroke) Pilot Clinical Trial used a multiple-tier, open-label, dose
      escalation design. Subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS]
      of 6 or above) received a 2-hour infusion of 25% human albumin (ALB) beginning
      within 16 hours of stroke onset. Six successive ALB dose tiers were assessed
      ranging from 0.34 to 2.05 g/kg. Neurologic and cardiac function was sequentially
      monitored. At 3 months, the NIHSS, modified Rankin Scale, and Barthel Index were
      measured. RESULTS: Eighty-two subjects (mean age, 65 years) received ALB at 7.8+/
      3.4 hours after stroke onset (mean+/-standard deviation). Forty-two patients also
      received standard-of-care intravenous tissue plasminogen activator (tPA). Vital
      signs were unaltered by ALB treatment. Dose-related increases in plasma albumin
      and mild hemodilution were maximal at 4 to 12 hours. Age-related plasma brain
      natriuretic peptide levels increased at 24 hours after ALB but did not predict
      cardiac adverse events. The sole ALB-related adverse event was mild or moderate
      pulmonary edema in 13.4% of subjects, which was readily managed with diuretics.
      In the tPA-treated subgroup, symptomatic intracranial hemorrhage occurred in only
      one of 42 subjects. CONCLUSIONS: Twenty-five percent human albumin in doses
      ranging up to 2.05 g/kg was tolerated by patients with acute ischemic stroke
      without major dose-limiting complications. tPA therapy did not affect the safety
      profile of ALB. The companion article presents neurologic outcome data and
      efficacy analysis in these subjects.

PMID- 16809572
TI  - Fn14 is upregulated in cytokine-stimulated vascular smooth muscle cells and is
      expressed in human carotid atherosclerotic plaques: modulation by atorvastatin.
AB  - BACKGROUND AND PURPOSE: Interaction between different members of the tumor
      necrosis factor superfamily and their receptors elicits diverse biologic actions
      that are implicated in the pathogenesis of atherosclerosis. We have analyzed the
      expression of Fn14 and its ligand TWEAK in carotid atherosclerotic plaques and
      its potential modulation by atorvastatin in vivo. Furthermore, we have studied
      whether proinflammatory cytokines regulate Fn14 expression in human aortic smooth
      muscle cells (hASMCs) in culture as well as the potential regulation by
      atorvastatin treatment. METHODS: Fn14 and TWEAK expression was analyzed in human
      carotid atherosclerotic plaques. Furthermore, Fn14 expression was studied in
      hASMCs in culture. RESULTS: Fn14 and TWEAK are expressed in macrophages and
      smooth muscle cells in carotid atherosclerotic plaques. Proinflammatory cytokines
      (interleukin-1beta and interferon-gamma) upregulate Fn14 expression in hASMCs.
      This effect was prevented by atorvastatin treatment and reversed by mevalonate
      and geranylgeranyl pyrophosphate. Geranylgeranyl transferase inhibitor, toxin B
      (Rac and Rho inhibitor), C3 exoenzyme (Rho inhibitor), and Y-27632 (Rho kinase
      inhibitor) also decreased Fn14 expression, implicating the Rho/Rho kinase pathway
      in the regulation of Fn14 expression. Finally, atorvastatin treatment reduced
      Fn14 expression in vivo. CONCLUSIONS: TWEAK and Fn14 are expressed in
      atherosclerotic plaques and could be novel mediators of atherosclerosis.
      Atorvastatin diminishes Fn14 expression in vitro and in vivo providing novel
      information of the beneficial properties of statins.

PMID- 16809573
TI  - Atrial fibrillation and stroke in the general medicare population: a 10-year
      perspective (1992 to 2002).
AB  - BACKGROUND AND PURPOSE: Clinical trials have illustrated warfarin's protective
      effect on stroke risk in patients with atrial fibrillation (AF). The current
      study investigated temporal trends in AF prevalence, warfarin use, and its
      relation to stroke risk in Medicare patients with AF from 1992 to 2002. METHODS:
      The Medicare 5% sample for 1992 to 2002 was used to create 1-year cohorts of
      patients with Medicare as primary payer throughout the year. International
      Classification of Diseases, Ninth Revision, Clinical Modification codes were used
      to identify AF, ischemic and hemorrhagic stroke, and comorbid conditions. A
      previously validated surrogate measure, prothrombin/international normalized
      ratio claims, was used to identify warfarin use. Cox proportional hazards
      regression was used to examine time to stroke with warfarin use as a time
      dependent variable. RESULTS: Among Medicare patients aged > or = 65 years, AF
      prevalence increased from 3.2% in 1992 to 6.0% in 2002 with higher prevalence in
      older subsets of the study population. Among patients with AF, warfarin use
      increased significantly (P< or = 0.001) for each year examined, from 24.5% in
      1992 to 56.3% in 2002. Stroke rates per 1000 patient-years declined from 46.7 in
      1992 to 19.5 in 2002 for ischemic stroke but remained fairly steady for
      hemorrhagic stroke (range, 1.6 to 2.9). Time-to-event modeling confirmed a
      protective association of warfarin against ischemic stroke among Medicare
      patients with AF. CONCLUSIONS: This analysis represents an observational
      validation of stroke prevention in AF trials. The significant increase in
      warfarin use among patients with AF illustrates diffusion of trial evidence into
      clinical practice.

PMID- 16809574
TI  - NXY-059: brain or vessel protection.

PMID- 16809576
TI  - Potential new risk factors for ischemic stroke: what is their potential?
AB  - BACKGROUND AND PURPOSE: About 60% to 80% of all ischemic strokes can be
      attributed to increasing blood pressure, blood cholesterol, cigarette smoking,
      carotid stenosis, and diabetes mellitus (atherosclerotic ischemic stroke), and
      atrial fibrillation and valvular heart disease (cardiogenic ischemic stroke). The
      aim of this review was to examine the potential role of other risk factors in the
      etiology of ischemic stroke. SUMMARY OF REVIEW: About 10% to 20% of
      atherosclerotic ischemic strokes can probably be attributed to recently
      established, causal risk factors for ischemic heart disease: raised apoB/apoA 1
      ratio, obesity, physical inactivity, pyschosocial stress and low fruit and
      vegetable intake. However, their causal role remains to be proven. The direct
      genetic contribution of any single gene towards ischemic stroke is likely to be
      modest and apply in selected patients only and in combination with environmental
      factors or via other epistatic (gene-gene or gene-environmental) effects.
      CONCLUSIONS: Research resources should not be allocated disproportionately to
      emerging novel risk factors that may account for up to only 20% of all strokes at
      the expense of researching the determinants of the relatively few established
      causal factors that account for up to 80% of all strokes.

PMID- 16809575
TI  - How valid are family proxy assessments of stroke patients' health-related quality
      of life?
AB  - BACKGROUND AND PURPOSE: Proxy respondents are often needed to report outcomes in
      stroke survivors, but they typically systematically rate impairments worse than
      patients themselves. The magnitude of this difference, the degree of agreement
      between patients and proxies, and the factors influencing agreement are not well
      known. METHODS: We compared patient and family proxy health-related quality of
      life (HRQL) responses in 225 patient-proxy pairs enrolled in a clinical trial for
      poststroke depression. We used paired t-tests and the intraclass correlation
      (ICC) statistic to evaluate the agreement between patient and proxy domain scores
      and the overall Stroke-specific Quality of Life (SS-QOL) score. We used
      multivariate linear regression to model patient- and proxy-reported SS-QOL
      scores. RESULTS: Patients were older (63 versus 55 years) and less often female
      (48% versus 74%) than proxies. Proxies rated all domains of SS-SQOL slightly
      worse than patients. The Mood, Energy, and Thinking domains had the greatest
      disparity with mean patient-proxy differences of 0.45, 0.37, and 0.37 points,
      respectively. The ICC for each domain ranged from 0.30 (role function) to 0.59
      (physical function). Proxy overall SS-QOL score was also lower (worse) than
      patient score (3.7 versus 3.4, P<0.001) with ICC of 0.41. Agreement was higher
      among patient-proxy pairs with higher patient depression scores and with lower
      proxy report of caregiving burden. CONCLUSIONS: Proxies systematically report
      more dysfunction in multiple aspects of HRQL than stroke patients themselves.
      Agreement between patient and proxy HRQL domain scores is modest at best and is
      affected by patient depression and proxy perception of burden. These differences
      may be large enough to impact the outcome assessment in stroke clinical trials.

PMID- 16809577
TI  - Screening for suicide risk.

PMID- 16809578
TI  - An old custom, a new threat to tobacco control.

PMID- 16809579
TI  - Andrija Stampar: charismatic leader of social medicine and international health.

PMID- 16809580
TI  - The impact of state laws limiting malpractice damage awards on health care
      expenditures.
AB  - Twenty-eight states have laws that limit payments in malpractice cases, and
      several studies indicate that these laws reduce the frequency and severity of
      malpractice claims and lower premiums. Moreover, proponents believe that such
      laws reduce health care expenditures by reducing the practice of defensive
      medicine. However, there is a dearth of empirical evidence about the impact of
      these laws on the cost of health care. We used multivariate models and relatively
      recent data to estimate the impact of state tort reform laws that directly limit
      malpractice damage payments on health care expenditures. Estimates from these
      models suggest that laws limiting malpractice payments lower state health care
      expenditures by between 3% and 4%.

PMID- 16809581
TI  - Relationships between self-reported unfair treatment and prescription medication
      use, illicit drug use, and alcohol dependence among Filipino Americans.
AB  - OBJECTIVES: We examined associations between self-reported unfair treatment and
      prescription medication use, illicit drug use, and alcohol dependence. METHODS:
      We used data from the Filipino American Community Epidemiological Survey, a cross
      sectional investigation involving 2217 Filipino Americans interviewed in 1998
      1999. Multinomial logistic and negative binomial regression analyses were used in
      assessing associations between unfair treatment and the substance use categories.
      RESULTS: Reports of unfair treatment were associated with prescription drug use,
      illicit drug use, and alcohol dependence after control for age, gender, location
      of residence, employment status, educational level, ethnic identity level,
      nativity, language spoken, marital status, and several health conditions.
      CONCLUSIONS: Unfair treatment may contribute to illness and subsequent use of
      prescription medications. Furthermore, some individuals may use illicit drugs and
      alcohol to cope with the stress associated with such treatment. Addressing the
      antecedents of unfair treatment may be a potential intervention route.

PMID- 16809582
TI  - Monitoring socioeconomic disparities in death: comparing individual-level
      education and area-based socioeconomic measures.
AB  - We compared all-cause mortality rates stratified by individual-level education
      and by census tract area-based socioeconomic measures for Massachusetts (1999
      2001). Among persons aged 25 and older, the age-adjusted relative index of
      inequality was slightly higher for the census tract than for the individual
      education measures (1.5 vs 1.2, respectively). Only the census tract
      socioeconomic measures could provide a relative index of inequality (2-3) for
      deaths before age 25 or detect expected socioeconomic disparities for deaths
      among persons 65 and older (relative index of inequality= approximately 1.2 vs
      0.8 for census tract measures and individual education, respectively).

PMID- 16809583
TI  - Cessation among smokers of "light" cigarettes: results from the 2000 national
      health interview survey.
AB  - OBJECTIVES: A large proportion of smokers erroneously believe that low
      nicotine/low-tar cigarettes, also called "light cigarettes" or "lights," reduce
      health risks and are a rational alternative to smoking cessation. However, the
      availability of light cigarettes may deter smoking cessation. METHODS: We
      analyzed the 32374 responses to the US 2000 National Health Interview Survey.
      Current and former smokers ("ever-smokers") were asked if they had ever used a
      lower tar and nicotine cigarette to reduce health risks. Multivariable logistic
      regression identified determinants of lights use and smoking cessation. Results
      were weighted to reflect the national population. RESULTS: Of 12285 ever-smokers,
      37% (N=4414) reported having used light cigarettes to reduce health risks.
      Current abstinence was less often reported by ever-smokers who had previously
      used light cigarettes than by ever-smokers who had never used lights (37% vs 53%,
      P<.01). Adjusted odds of cessation among ever-smokers who had used light
      cigarettes relative to those who had never used lights were reduced by 54%
      (adjusted odds ratio=0.46, 95% confidence interval=0.41, 0.51). CONCLUSIONS: Use
      of light cigarettes was common and was associated with lower odds of current
      smoking cessation, validating the concern that smokers may use lights as an
      alternative to cessation.

PMID- 16809584
TI  - Public health and the anticorporate movement: rationale and recommendations.
AB  - Institutions and informal networks have formed a movement that is challenging the
      growing power and pervasive influence of large corporations. The movement's
      analyses show that the historical development and current function of the
      corporate entity requires production of a profit regardless of consequences to
      health, society, or the environment. As a result, public health professionals
      frequently address health problems related to products, services, or practices of
      corporations. There are possibilities for links between public health and the
      anticorporate movement. Public health research and the professional preparation
      curriculum should focus on the corporate entity as a social structural
      determinant of disease.

PMID- 16809585
TI  - Orphan care in Botswana's working households: growing responsibilities in the
      absence of adequate support.
AB  - OBJECTIVES: Botswana has one of the world's highest HIV-prevalence rates and the
      world's highest percentages of orphaned children among its population. We
      assessed the ability of income-earning households in Botswana to adequately care
      for orphans. METHODS: We used data from the Botswana Family Health Needs Study
      (2002), a sample of 1033 working adults with caregiving responsibilities who used
      public services, to assess whether households with orphan-care responsibilities
      encountered financial and other difficulties. Thirty-seven percent of respondents
      provided orphan care, usually to extended family members. We applied logistic
      regression models to determine the factors associated with experiencing problems
      related to orphan caregiving. RESULTS: Nearly half of working households with
      orphan-care responsibilities reported experiencing financial and other
      difficulties because of orphan care. Issues of concern included caring for
      multiple orphans, caring for sick adults and orphans simultaneously, receiving no
      assistance, and low income. CONCLUSIONS: The orphan crisis is impoverishing even
      working households, where caregivers lack sufficient resources to provide basic
      needs. Neither the public sector nor communities provide adequate safety nets.
      International assistance is critical to build capacity within the social welfare
      infrastructure and to fund community-level activities that support households.
      Lessons from Botswana's orphan crisis can provide valuable insights to
      policymakers throughout sub-Saharan Africa.

PMID- 16809586
TI  - Edentulism among Mexican adults aged 35 years and older and associated factors.
AB  - We used National Performance Evaluation Survey data to estimate the prevalence
      and associated factors of edentulism among noninstitutionalized adults aged 35
      years and older in Mexico. Statistically, the variables positively associated
      with edentulism were older age (odds ratio [OR]=1.08) and female gender
      (OR=1.79). Nonsmoking status (OR=0.70) and having a higher wealth index score
      (OR=0.72) were negatively associated. This information constitutes the first
      large-scale evaluation in Mexico for one of the World Health Organization's
      priority oral health problems.

PMID- 16809587
TI  - Racial/ethnic disparities in report of physician-provided smoking cessation
      advice: analysis of the 2000 National Health Interview Survey.
AB  - OBJECTIVES: We explored racial/ethnic disparities in reports of smoking cessation
      advice among smokers who had visited a physician in the previous year. Also, we
      examined the likelihood of receipt of such advice across Hispanic subgroups and
      levels of English proficiency. METHODS: We analyzed data from the 2000 National
      Health Interview Survey. RESULTS: Nearly half of the 5652 respondents reported
      receiving smoking cessation advice from their doctor. Compared with Hispanics,
      and after control for a range of other factors, respondents in the non-Hispanic
      White (adjusted odds ratio [OR]=1.57, 95% confidence interval [CI]=1.2, 2.0), non
      Hispanic Black (adjusted OR=1.44, 95% CI=1.0, 2.0), and other non-Hispanic
      (adjusted OR=2.19, 95% CI=1.3, 3.6) groups were significantly more likely to
      report receiving advice. English proficiency was not associated with receipt of
      physician advice among Hispanic smokers. CONCLUSIONS: Some 16 million smokers in
      the United States could not recall receiving advice to quit smoking from their
      physician in the preceding year. These missed opportunities, compounded by
      racial/ethnic disparities such as those observed between Hispanics and other
      groups and between Hispanic subgroups, suggest that considerably greater effort
      is needed to diminish the toll stemming from smoking and smoking-related
      diseases.

PMID- 16809588
TI  - Effect of increased social unacceptability of cigarette smoking on reduction in
      cigarette consumption.
AB  - Taxes on cigarettes have long been used to help reduce cigarette consumption.
      Social factors also affect cigarette consumption, but this impact has not been
      quantified. We computed a social unacceptability index based on individuals'
      responses to questions regarding locations where smoking should be allowed. A
      regression analysis showed that the social unacceptability index and price had
      similar elasticities and that their effects were independent of each other. If,
      through an active tobacco control campaign, the average individual's views on the
      social unacceptability of smoking changed to more closely resemble the views of
      California residents, there would be a 15% drop in cigarette consumption,
      equivalent to a 1.17 dollars increase in the excise tax on cigarettes.

PMID- 16809589
TI  - Parental English proficiency and children's health services access.
AB  - OBJECTIVES: We examined the relation between parents' level of English
      proficiency and their children's access to health care. METHODS: Using the 2001
      California Health Interview Survey, we conducted bivariate and multivariate
      analyses of several measures of children's access to health care (current health
      insurance status, usual source of care, emergency room visits, delayed or forgone
      care, traveling to another country for health care, and perceived discrimination
      in health care) and their association with parents' English proficiency. RESULTS:
      Compared with English-speaking households, children in non-English-speaking
      households were more likely to lack health insurance, to not have doctor contact,
      and to go to other countries for health care and were less likely to use
      emergency rooms. Their parents were less likely to report their children's
      experiencing delayed or forgone care or discrimination in health care.
      CONCLUSION: English proficiency is a strong predictor of access to health
      insurance for children, and children in non-English-speaking families are
      especially likely to rely on other countries for their health care. English
      proficiency may mitigate the effects of race/ethnicity commonly observed in
      health care access and utilization studies.

PMID- 16809590
TI  - A comparison of the health and mental health status of homeless mothers in
      Worcester, Mass: 1993 and 2003.
AB  - OBJECTIVES: We assessed background characteristics, health status, and prevalence
      rates of mental health disorders in 2 studies of homeless mothers conducted in
      Worcester, Mass, one in 1993 and the other in 2003. METHODS: We compared the
      women taking part in the 2 studies, which involved similar methodologies, on the
      key variables of interest over time. RESULTS: Homeless families taking part in
      the 2003 study were poorer than those taking part in the 1993 study, and female
      heads of household in that study reported more physical health limitations, major
      depressive illness, and posttraumatic stress disorder. CONCLUSION: Data from 2003
      suggest that the characteristics of homeless mothers changed over the 10-year
      period assessed. Service providers and shelter staff may need to refine services
      so that they are responsive to these changing needs.

PMID- 16809591
TI  - Efficacy vs effectiveness trial results of an indicated "model" substance abuse
      program: implications for public health.
AB  - OBJECTIVES: The US Department of Education requires schools to choose substance
      abuse and violence prevention programs that meet standards of effectiveness. The
      Substance Abuse and Mental Health Services Agency certifies "model" programs that
      meet this standard. We compared findings from a large, multisite effectiveness
      trial of 1 model program to its efficacy trial findings, upon which the
      certification was based. METHODS: 1370 high-risk youths were randomized to
      experimental or control groups across 9 high schools in 2 large urban school
      districts. We used intent-to-treat and on-treatment approaches to examine
      baseline equivalence, attrition, and group differences in outcomes at the end of
      the program and at a 6-month follow-up. RESULTS: Positive efficacy trial findings
      were not replicated in the effectiveness trial. All main effects were either null
      or worse for the experimental than for the control group. CONCLUSIONS: These
      findings suggest that small efficacy trials conducted by developers provide
      insufficient evidence of effectiveness. Federal agencies and public health
      scientists must work together to raise the standards of evidence and ensure that
      data from new trials are incorporated into ongoing assessments of program
      effects.

PMID- 16809592
TI  - Sustainability of public health programs: the example of tobacco treatment
      services in Massachusetts.
AB  - Sustaining important public or grant-funded services after initial funding is
      terminated is a major public health challenge. We investigated whether tobacco
      treatment services previously funded within a statewide tobacco control
      initiative could be sustained after state funding was terminated abruptly. We
      found that 2 key strategies-redefining the scope of services being offered and
      creative use of resources-were factors that determined whether some community
      agencies were able to sustain services at a much higher level than others after
      funding was discontinued. Understanding these strategies and developing them at a
      time when program funding is not being threatened is likely to increase program
      sustainability.

PMID- 16809593
TI  - Educational inequalities in initiation, cessation, and prevalence of smoking
      among 3 Italian birth cohorts.
AB  - OBJECTIVES: We examined socioeconomic inequalities in initiation and cessation
      rates of smoking and the resultant inequality in smoking prevalence among 3
      consecutive Italian birth cohorts. METHODS: We used data from the 1999-2000
      Italian National Health Interview Survey, which included 28958 men and 29769
      women who were born between 1940 and 1969. The association between smoking
      variables and level of education was assessed with logistic regression and life
      table analyses. RESULTS: Inequalities in the lifetime prevalence of smoking
      increased across the 3 birth cohorts in Italy. At age 40, lower-educated persons
      in the youngest cohort reported on average 1 to 5 years of additional exposure to
      regular smoking compared with higher-educated persons. Inequalities in smoking
      prevalence increased among both men and women because of widening inequalities in
      initiation rates. Among women, growing inequalities in cessation rates also
      played a role. CONCLUSIONS: The relative contribution of initiation and cessation
      to socioeconomic inequalities in smoking rates varied by both gender and birth
      cohort. For the youngest birth cohort, policies that address inequalities in
      smoking should focus on both initiation and cessation.

PMID- 16809594
TI  - Effects of domestic violence on perinatal and early-childhood mortality: evidence
      from north India.
AB  - OBJECTIVE: We examined the effect of physical violence during pregnancy on
      perinatal and early-childhood mortality. METHODS: We estimated the prevalence of
      domestic violence during pregnancy among a population-based sample of 2199 women
      in Uttar Pradesh, India. We used a survival regression model to examine the risks
      for perinatal, neonatal, postneonatal, and early-childhood (aged 1-3 years)
      mortality by mother's exposure to domestic violence, after we controlled for
      other sociodemographic and maternal health behavior risk factors. RESULTS:
      Eighteen percent of the women in our study experienced domestic violence during
      their last pregnancy. After we adjusted for other risk factors, births among
      mothers who had experienced domestic violence had risks for perinatal and
      neonatal mortality that were 2.59 (95% confidence interval [CI]=1.35, 4.95) and
      2.37 (95% CI=1.21, 4.62) times higher, respectively, than births among mothers
      who had not experienced violence. We found no significant associations between
      domestic violence and either postneonatal or early-childhood mortality.
      CONCLUSIONS: Domestic violence is a significant risk factor for perinatal and
      neonatal mortality.

PMID- 16809595
TI  - Neighborhood social capital and dental injuries in Brazilian adolescents.
AB  - OBJECTIVES: Evidence suggests that communities with higher levels of social
      capital have better health, but this association has not been explored
      specifically in relation to dental injury. We investigated the association
      between social capital and dental injury. METHODS: We conducted a multilevel
      study assessed individual and neighborhood effects on dental injury of 1302 14-
      to 15-year-old adolescents in 39 schools of Distrito Federal, Brazil. Children
      underwent a dental examination and, with their parents, answered a questionnaire
      about their local environments. Our data analysis used logistic multilevel
      modeling of students and neighborhood (the latter defined by catchment areas of
      schools). RESULTS: The prevalence of dental injury was significantly lower in
      neighborhoods with higher levels of social capital, especially among boys. After
      control for individual and neighborhood variables, the adjusted odds ratio for a
      1-unit increase in the standardized social capital index was 0.55 (95% confidence
      interval=0.37, 0.81; P=.002) among boys. CONCLUSIONS: Social capital may explain
      inequalities in rates of dental injury, especially among boys.

PMID- 16809596
TI  - Asbestos-related disease in South Africa: the social production of an invisible
      epidemic.
AB  - South Africa was the third largest exporter of asbestos in the world for more
      than a century. As a consequence of particularly exploitative social conditions,
      former workers and residents of mining regions suffered--and continue to suffer-
      from a serious yet still largely undocumented burden of asbestos-related disease.
      This epidemic has been invisible both internationally and inside South Africa. We
      examined the work environment, labor policies, and occupational-health framework
      of the asbestos industry in South Africa during the 20th century. In a changing
      local context where the majority of workers were increasingly disenfranchised,
      unorganized, excluded from skilled work, and predominantly rural, mining
      operations of the asbestos industry not only exposed workers to high levels of
      asbestos but also contaminated the environment extensively.

PMID- 16809597
TI  - Toward a theory-driven model of acculturation in public health research.
AB  - Interest in studying the impact of acculturation on immigrant health has
      increased in tandem with the growth of the Latino population in the United
      States. Linear assimilation models continue to dominate public health research
      despite the availability of more complex acculturation theories that propose
      multidimensional frameworks, reciprocal interactions between the individual and
      the environment, and other acculturative processes among various Latino groups.
      Because linear and unidimensional assessments (e.g., nativity, length of stay in
      the United States, and language use) provide constricted measures of
      acculturation, the rare use of multidimensional acculturation measures and models
      has inhibited a more comprehensive understanding of the association between
      specific components of acculturation and particular health outcomes. A public
      health perspective that incorporates the roles of structural and cultural forces
      in acculturation may help identify mechanisms underlying links between
      acculturation and health among Latinos.

PMID- 16809598
TI  - Ten years and 1 master settlement agreement later: the nature and frequency of
      alcohol and tobacco promotion in televised sports, 2000 through 2002.
AB  - OBJECTIVES: I sought to identify what kinds of promotion for alcohol and tobacco
      products are found in televised sports programming, as well as how frequently
      they occur. I compared my findings with data from 5 and 10 years earlier to
      examine the effects of the Master Settlement Agreement and detect industry
      trends. Method. A content analysis of more than 83 hours of televised sports
      programming from 2000 through 2002 was conducted. Composite week sampling was
      used to ensure results were representative of the overall population of
      television sports programs. Programs were examined for traditional advertising
      (commercials) and nontraditional advertising (stadium signs, announcer
      voiceovers, etc.). RESULTS: Rates of certain types of alcohol advertising have
      decreased, but what remains is strategically chosen to increase the likelihood of
      audience exposure. Despite the Master Settlement Agreement, tobacco advertising
      remains prevalent in many sports. A new trend of placing alcohol and tobacco
      brand names in commercials for other products is evident. CONCLUSIONS: Alcohol
      and tobacco marketers appear able to cleverly adapt to advertising challenges,
      such as digital video recorders and legislation. Alcohol and tobacco brands
      remain visible on sports programming.

PMID- 16809599
TI  - Psychosocial care for adult and child survivors of the 2004 tsunami disaster in
      India.
AB  - The tsunami disaster in South Asia affected the mental health of thousands of
      survivors, but psychological aspects of rehabilitation are frequently overlooked
      in public health initiatives. From January to March 2005, teams from the National
      Institute of Mental Health and Neurosciences in Bangalore, India, traveled to
      south India and implemented a "train the trainer" community-based mental health
      program of psychosocial care to facilitate the recovery of child and adult
      survivors. Psychosocial care has applications to natural and man-made disasters
      in developing countries.

PMID- 16809600
TI  - Hospital religious affiliation and emergency contraceptive prescribing practices.
AB  - With access to reproductive health care eroding, examination of prescribing of
      contraception, including emergency contraception (EC), is important. We examined
      whether working in a family practice affiliated with a religious institution
      changes the likelihood of a provider prescribing EC. Our survey asked about EC
      prescribing practices in a range of situations. As predicted, practitioners in
      non-religiously affiliated practices reported higher rates of prescribing EC than
      those in religiously affiliated practices. In both cases, however, the
      practitioners' prescribing patterns were inadequate.

PMID- 16809601
TI  - Diffusion of the D.A.R.E and syringe exchange programs.
AB  - We examined the diffusion of the D.A.R.E program to reduce use of illicit drugs
      among school-aged children and youths and the diffusion of syringe exchange
      programs to reduce HIV transmission among injection drug users. The D.A.R.E
      program was diffused widely in the United States despite a lack of evidence for
      its effectiveness; there has been limited diffusion of syringe exchange in the
      United States, despite extensive scientific evidence for its effectiveness.
      Multiple possible associations between diffusion and evidence of effectiveness
      exist, from widespread diffusion without evidence of effectiveness to limited
      diffusion with strong evidence of effectiveness. The decision theory concepts of
      framing and loss aversion may be useful for further research on the diffusion of
      public health innovations.

PMID- 16809602
TI  - Interpersonal violence among women seeking welfare: unraveling lives.
AB  - OBJECTIVES: Exposure to violence is a widespread problem among women who receive
      welfare benefits. Research has focused on partner violence among women with
      children on Temporary Assistance for Needy Families (TANF), ignoring low-income
      women without dependent children who are eligible for General Assistance (GA).
      METHODS: We report findings from a survey of 1235 women seeking TANF (N=1095) and
      GA (N=140) throughout a California county. RESULTS: Estimates of recent physical,
      sexual, and severe violence were high in both populations. However, the highest
      rates occurred among women without children seeking GA, suggesting that they are
      at higher risk for sexual violence and more severe forms of physical violence,
      especially from intimate partners. This increased risk is partly accounted for by
      the co-occurrence of other serious health and social problems. In multivariate
      analyses, past-year violence was associated with substance use (adjusted odds
      ratio [AOR]=2.0, 95% confidence interval [CI] = 1.5, 2.9), recent homelessness
      (AOR = 1.9, 95% CI = 1.4, 2.6), family fragmentation including divorce or
      separation (AOR=3.1, 95% CI 1.8, 5.2), or foster care involvement (AOR=2.2, 95%
      CI=1.1, 4.5) CONCLUSIONS: Welfare reform created TANF programs to address
      domestic violence. Women seeking GA may need similar services because of the high
      prevalence of violence.

PMID- 16809603
TI  - Effects of job strain on blood pressure: a prospective study of male and female
      white-collar workers.
AB  - OBJECTIVES: We evaluated whether cumulative exposure to job strain increases
      blood pressure. METHODS: A prospective study of 8395 white-collar workers was
      initiated during 1991 to 1993. At follow-up, 7.5 years later, 84% of the
      participants were reassessed to estimate cumulative exposure to job strain.
      RESULTS: Compared with men who had never been exposed, men with cumulative
      exposure and those who became exposed during follow-up showed significant
      systolic blood pressure increments of 1.8 mm Hg (95% confidence interval
      [CI]=0.1, 3.5) and 1.5 mm Hg (95% CI=0.2, 2.8), respectively, and relative risks
      of blood pressure increases in the highest quintile group of 1.33 (95% CI = 1.01,
      1.76) and 1.40 (95% CI = 1.14, 1.73). Effect magnitudes were smaller among women.
      Effects tended to be more pronounced among men and women with low levels of
      social support at work. CONCLUSIONS: Among these white-collar workers, exposure
      to cumulative job strain had a modest but significant effect on systolic blood
      pressure among men. The risk was of comparable magnitude to that observed for age
      and sedentary behavior. Men and women with low levels of social support at work
      appeared to be at higher risk for increases in blood pressure.

PMID- 16809604
TI  - Interpersonal violence in the lives of urban American Indian and Alaska Native
      women: implications for health, mental health, and help-seeking.
AB  - OBJECTIVE: We surveyed American Indian/Alaska Native (AIAN) women in New York
      City to determine the prevalence of 3 types of interpersonal violence among urban
      AIAN women and the behavioral health and mental health factors associated with
      this violence. METHODS: Using a survey, we questioned 112 adult AIAN women in New
      York City about their experiences with interpersonal violence, mental health, HIV
      risk behaviors, and help-seeking. The sampling plan utilized a multiple-wave
      approach with modified respondent-driven sampling, chain referral, and target
      sampling. RESULTS: Among respondents, over 65% had experienced some form of
      interpersonal violence, of which 28% reported childhood physical abuse, 48%
      reported rape, 40% reported a history of domestic violence, and 40% reported
      multiple victimization experiences. Overwhelmingly, women experienced high levels
      of emotional trauma related to these events. A history of interpersonal violence
      was associated with depression, dysphoria, help-seeking behaviors, and an
      increase in high-HIV risk sexual behaviors. CONCLUSIONS: AIAN women experience
      high rates of interpersonal violence and trauma that are associated with a host
      of health problems and have important implications for health and mental health
      professionals.

PMID- 16809605
TI  - Variations in the health conditions of 6 Chicago community areas: a case for
      local-level data.
AB  - OBJECTIVES: Although local-level chronic disease and risk factor data are not
      typically available, they are valuable for guiding public health interventions
      and policies. To present a case for disaggregated community-level health data, we
      conducted a study exploring the relevance of such data to research on health
      disparities. METHODS: We designed a population-based health survey to gather
      information on many health measures, 13 of which are presented here. Interviews
      were conducted with 1699 adults (18-75 years) in 6 Chicago community areas
      between September 2002 and April 2003. RESULTS: Statistically significant
      variations in health measures were found between the 6 communities themselves
      (108 of 195 pairwise comparisons were significant) and between the communities
      and Chicago as a whole (35 of 54 comparisons were significant). CONCLUSIONS: The
      local-level variations in health revealed in this study emphasize that geographic
      and racial/ethnic health disparities are still prominent in Chicago and shed
      light on the limitations of existing city- and regional-level data.

PMID- 16809606
TI  - Organization and financing of alcohol and substance abuse programs for American
      Indians and Alaska Natives.
AB  - OBJECTIVES: Although American Indians and Alaska Natives have high rates of
      substance abuse, few data about treatment services for this population are
      available. We used national data from 1997-2002 to describe recent trends in
      organizational and financial arrangements. METHODS: Using data from the Indian
      Health Service (IHS), the Substance Abuse and Mental Health Services
      Administration, the National Institute on Alcohol Abuse and Alcoholism, the Henry
      J. Kaiser Family Foundation, and the Census Bureau, we estimated the number of
      American Indians served by substance abuse treatment programs that apparently are
      unaffiliated with either the IHS or tribal governments. We compared expected and
      observed IHS expenditures. RESULTS: Half of the American Indians and Alaska
      Natives treated for substance abuse were served by programs (chiefly in urban
      areas) apparently unaffiliated with the IHS or tribal governments. IHS substance
      abuse expenditures were roughly what we expected. Medicaid participation by
      tribal programs was not universal. CONCLUSIONS: Many Native people with substance
      abuse problems are served by programs unaffiliated with the IHS. Medicaid may be
      key to expanding needed resources.

PMID- 16809607
TI  - Increased access to unrestricted pharmacy sales of syringes in Seattle-King
      County, Washington: structural and individual-level changes, 1996 versus 2003.
AB  - We examined pharmacists' attitudes and practices related to syringe sales to
      injection drug users before and after legal reform and local programming to
      enhance sterile syringe access. We replicated a 1996 study by conducting
      pharmacist phone surveys and syringe test-buys in randomly selected pharmacies.
      Test-buy success increased from 48% in 1996 to 65% in 2003 (P=.04). Pharmacists
      agreeing that syringes should be available to injection drug users through
      pharmacy purchase increased from 49% to 71% (P<.01). Pharmacy policies and
      pharmacist attitudes were strongly associated with syringe access. Structural
      changes, including policy reform and pharmacy outreach, appear to increase
      syringe access. Interventions should address pharmacy policies and pharmacist
      attitudes and policies.

PMID- 16809608
TI  - Social capital and health: civic engagement, community size, and recall of health
      messages.
AB  - OBJECTIVES: We explored the effects of community integration and pluralism on
      recall of cardiovascular disease health information messages. METHODS: With 1980
      1983 data from the Minnesota Heart Health Program, we examined whether ties to
      community groups were associated with recall of health messages, and whether this
      relation was modified by size and degree of differentiation of the community.
      RESULTS: A higher level of civic engagement through ties to community groups was
      associated with better recall of health messages. Ties to community groups
      independently contributed to better message recall even after control for gender,
      education, and other variables. The moderating role of community size was non
      significant but intriguing. CONCLUSIONS: Community group membership could
      increase exposure to health messages, providing a critical pathway for social
      capital to influence health promotion and, thus, public health outcomes.

PMID- 16809609
TI  - Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular
      fetal thymus colonization.
AB  - Thymus seeding by T-lymphoid progenitor cells is a prerequisite for T-cell
      development. However, molecules guiding thymus colonization and their roles
      before and after thymus vascularization are unclear. Here we show that mice
      doubly deficient for chemokine receptors CCR7 and CCR9 were defective
      specifically in fetal thymus colonization before, but not after, thymus
      vascularization. The defective prevascular fetal thymus colonization was followed
      by selective loss of the first wave of T-cell development generating epidermal
      Vgamma3(+) gammadelta T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed
      not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid
      primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1
      dependent thymic primordium, revealing the role of the adjacent parathyroid in
      guiding fetal thymus colonization. These results indicate coordination between
      Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing
      CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular
      fetal thymus colonization.

PMID- 16809612
TI  - Neutrophils from patients with heterozygous germline mutations in the von Hippel
      Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial
      phagocytosis.
AB  - Neutrophils are key mediators of the innate immune response and are required to
      function at sites of low oxygenation. We have shown that in hypoxia neutrophils
      are protected from apoptosis via a mechanism dependent on prolyl hydroxylase
      domain/hypoxia-inducible factor 1alpha (PHD/HIF-1alpha). This response would be
      predicted to involve the von Hippel Lindau protein (pVHL)-dependent
      ubiquitination and degradation of HIF-1alpha. Patients with VHL disease inherit a
      mutation in one VHL allele, which allows us to study the effects of heterozygous
      VHL expression in human neutrophils. Neutrophils exhibited a striking "partial
      hypoxic" pheno-type, with delayed rates of apoptosis and enhanced bacterial
      phagocytosis under normoxic conditions and preserved responses to low levels of
      oxygen. This provides direct evidence that the HIF-1alpha/VHL pathway regulates
      the innate immune response in humans. It also establishes that heterozygous VHL
      defects are sufficient to perturb normal responses and illustrates the potential
      to use this to address the role of HIF and VHL in human biology.

PMID- 16809610
TI  - Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate
      extracted from green tea: biologic activity and therapeutic implications.
AB  - Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an
      antioxidant with chemopreventive and chemotherapeutic actions. Based on its
      ability to modulate growth factor-mediated cell proliferation, we evaluated its
      efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent
      growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6
      dependent cells and primary patient cells, without significant effect on the
      growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts.
      Treatment with EGCG also led to significant apoptosis in human myeloma cells
      grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1
      (LR1), which is significantly elevated in myeloma cell lines and patient samples
      relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation
      of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an
      important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation
      of changes in gene expression profile indicates that EGCG treatment activates
      distinct pathways of growth arrest and apoptosis in MM cells by inducing the
      expression of death-associated protein kinase 2, the initiators and mediators of
      death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like
      proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation
      (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18).
      Expression of related genes at the protein level were also confirmed by Western
      blot analysis. These data demonstrate potent and specific antimyeloma activity of
      EGCG and provide the rationale for its clinical evaluation.

PMID- 16809611
TI  - BCL11B participates in the activation of IL2 gene expression in CD4+ T
      lymphocytes.
AB  - BCL11A and BCL11B are transcriptional regulators important for lymphopoiesis and
      previously associated with hematopoietic malignancies. Ablation of the mouse
      Bcl11b locus results in failure to generate double-positive thymocytes,
      implicating a critical role of Bcl11b in T-cell development. However, BCL11B is
      also expressed in CD4+ T lymphocytes, both in resting and activated states. Here
      we show both in transformed and primary CD4+ T cells that BCL11B participates in
      the control of the interleukin-2 (IL2) gene expression following activation
      through T-cell receptor (TCR). BCL11B augments expression from the IL2 promoter
      through direct binding to the US1 site. In addition, BCL11B associates with the
      p300 coactivator in CD4+ T cells activated through TCR, which may account for its
      transcriptional activation function. These results provide the first evidence
      that BCL11B, originally described as a transcriptional repressor, activates
      transcription of a target gene in the context of T-cell activation.

PMID- 16809613
TI  - VCAM-1 expression on dystrophic muscle vessels has a critical role in the
      recruitment of human blood-derived CD133+ stem cells after intra-arterial
      transplantation.
AB  - Recently our group demonstrated the myogenic capacity of human CD133(+) cells
      isolated from peripheral blood when delivered in vivo through the arterial
      circulation into the muscle of dystrophic scid/mdx mice. CD133(+) stem cells
      express the adhesion molecules CD44, LFA-1, PSGL-1, alpha4-integrins, L-selectin,
      and chemokine receptor CCR7. Moreover these cells adhere in vitro to VCAM-1
      spontaneously and after stimulation with CCL19. Importantly, after muscle
      exercise, we found that the expression of VCAM-1 is strongly up-regulated in
      dystrophic muscle vessels, whereas the number of rolling and firmly adhered
      CD133(+) stem cells significantly increased. Moreover, human dystrophin
      expression was significantly increased when muscle exercise was performed 24
      hours before the intra-arterial injection of human CD133(+) cells. Finally,
      treatment of exercised dystrophic mice with anti-VCAM-1 antibodies led to a
      dramatic blockade of CD133(+) stem cell migration into the dystrophic muscle. Our
      results show for the first time that the expression of VCAM-1 on dystrophic
      muscle vessels induced by exercise controls muscle homing of human CD133(+) stem
      cells, opening new perspectives for a potential therapy of muscular dystrophy
      based on the intra-arterial delivery of CD133(+) stem cells.

PMID- 16809614
TI  - Myelodysplastic syndromes and acute leukemia developing after imatinib mesylate
      therapy for chronic myeloid leukemia.
AB  - During therapy with imatinib, some patients with chronic myeloid leukemia (CML)
      develop chromosomal abnormalities in Philadelphia chromosome (Ph)-negative cells.
      These abnormalities are frequently transient and their clinical consequence is
      unclear. Although some reports have suggested that the abnormalities might be
      associated with secondary myelodysplastic syndrome (MDS), the diagnosis has not
      always been established using standard criteria. We report 3 cases of patients
      treated with imatinib for CML who were subsequently found to have chromosomal
      abnormalities in Ph-negative cells. One of them developed acute myelogenous
      leukemia (AML) and the other 2 developed high-risk MDS that rapidly transformed
      to AML. These cases were identified in a total study group of 1701 patients.
      Although these occurrences are rare, the findings highlight the need for close
      monitoring of patients with CML treated with imatinib.

PMID- 16809615
TI  - FLT3 internal tandem duplication in CD34+/CD33- precursors predicts poor outcome
      in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a clonal disease characterized by heterogeneous
      involvement of hematopoietic stem cell/progenitor cell populations. Using FLT3
      internal tandem duplication (FLT3/ITD) as a molecular marker, we tested the
      hypothesis that clinical outcome in AML correlates with disease involvement of
      CD34(+)/CD33(-) precursors. Diagnostic specimens from 24 children with FLT3/ITD
      positive AML were sorted by fluorescence-activated cell sorting (FACS), and
      resultant CD34(+)/CD33(-) and CD34(+)/CD33(+) progenitors were analyzed directly
      and after colony-forming cell (CFC) assay for the presence of FLT3/ITD. FLT3/ITD
      was present in all CD34(+)/CD33(+) patient samples. In contrast, FLT3/ITD was
      detected in CD34(+)/CD33(-) progenitors in only 19 of 24 samples. A bipotent
      progenitor was affected in a subset of patients, as evidenced by the presence of
      FLT3/ITD in both granulocyte-macrophage colony-forming unit (CFU-GM) and
      erythroid burst-forming unit (BFU-E) colonies. Those patients in whom
      CD34(+)/CD33(-) precursors harbored the FLT3/ITD had worse clinical outcome;
      actuarial event-free survival (EFS) at 4 years from study entry for those
      patients with and without FLT3/ITD detection in CD34(+)/CD33(-) progenitors was
      11% +/- 14% versus 100% +/- 0%, respectively (P = .002). This study suggests that
      FLT3/ITD involvement in CD34(+)/CD33(-) precursors is heterogeneous and that
      detection of the mutation in the less-mature progenitor population may be
      associated with disease resistance.

PMID- 16809616
TI  - B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and
      gain cytotoxic potential after interleukin-21-based activation.
AB  - B cells currently are not viewed as being capable of producing granzyme B or
      being cytotoxic. We found that B-chronic lymphocytic leukemia (B-CLL) cells
      treated with interleukin-21 (IL-21) produce low levels of granzyme B. The
      addition of either CpG oligodeoxynucleotide (ODN) or anti-B-cell-receptor
      antibody (anti-BCR) to IL-21 results in enhanced production of functional
      granzyme B by B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN undergo
      apoptosis and are able to induce apoptosis of untreated bystander B-CLL cells.
      This effect can be inhibited by anti-granzyme B antibody. Benign human B cells,
      Epstein-Barr virus (EBV)-transformed lymphoblasts, and many standard lymphoma
      cell lines produce high levels of granzyme B in response to IL-21 and anti-BCR.
      Our results suggest that the ability to induce production of functional granzyme
      B by B cells could open new approaches to the therapy of B-CLL and other B-cell
      malignancies. Our findings also have significant implications for our
      understanding of the role of B cells for immune regulation and for a variety of
      immune phenomena, including cancer immunity, autoimmunity, and infectious
      immunity.

PMID- 16809617
TI  - Development of a macrophage-based nanoparticle platform for antiretroviral drug
      delivery.
AB  - Complex dosing regimens, costs, side effects, biodistribution limitations, and
      variable drug pharmacokinetic patterns have affected the long-term efficacy of
      antiretroviral medicines. To address these problems, a nanoparticle indinavir (NP
      IDV) formulation packaged into carrier bone marrow-derived macrophages (BMMs) was
      developed. Drug distribution and disease outcomes were assessed in immune
      competent and human immunodeficiency virus type 1 (HIV-1)-infected humanized
      immune-deficient mice, respectively. In the former, NP-IDV formulation contained
      within BMMs was adoptively transferred. After a single administration, single
      photon emission computed tomography, histology, and reverse-phase-high
      performance liquid chromatography (RP-HPLC) demonstrated robust lung, liver, and
      spleen BMMs and drug distribution. Tissue and sera IDV levels were greater than
      or equal to 50 microM for 2 weeks. NP-IDV-BMMs administered to HIV-1-challenged
      humanized mice revealed reduced numbers of virus-infected cells in plasma, lymph
      nodes, spleen, liver, and lung, as well as, CD4(+) T-cell protection. We conclude
      that a single dose of NP-IDV, using BMMs as a carrier, is effective and warrants
      consideration for human testing.

PMID- 16809618
TI  - Induction of antigen-specific tolerance by intrathymic injection of lentiviral
      vectors.
AB  - Immune tolerance to self-antigens is established during lymphocyte
      differentiation in the thymus, but a simple means to induce antigen-specific
      tolerance in the thymus is still elusive. We show here that intrathymic injection
      of a lentiviral vector expressing the hemagglutinin antigen (HA) in TCR-HA
      transgenic mice resulted in negative selection of HA-specific effector T cells
      and sustained positive selection of HA-specific regulatory T cells (Tregs). This
      positive selection increased the number of HA-specific Tregs 10-fold and was
      comparable with the one observed in TCR-HA transgenic mice crossed with
      transgenic mice expressing HA under the control of the insulin promoter (Ins-HA).
      HA expression by radioresistant thymic epithelial cells was sufficient to drive
      Treg generation. Intrathymic injection of the lentiviral vector also resulted in
      an enrichment of HA-specific Tregs in peripheral lymphoid organs, which prevented
      diabetes induced in Ins-HA mice by transfer of HA-specific effector T cells. In
      this model, HA-specific Tregs inhibited effector T-cell division in pancreatic
      lymph nodes. Finally, we show that intrathymic injection of a lentiviral vector
      expressing preproinsulin-2 could reduce the occurrence of spontaneous diabetes in
      nonobese diabetic mice. Intrathymic gene transfer using lentiviral vectors thus
      offers new means to manipulate antigen-specific tolerance.

PMID- 16809619
TI  - Rac1 links leading edge and uropod events through Rho and myosin activation
      during chemotaxis.
AB  - Chemotactic responsiveness is crucial to neutrophil recruitment to sites of
      infection. During chemotaxis, highly divergent cytoskeletal programs are executed
      at the leading and trailing edge of motile neutrophils. The Rho family of small
      GTPases plays a critical role in cell migration, and recent work has focused on
      elucidating the specific roles played by Rac1, Rac2, Cdc42, and Rho during
      cellular chemotaxis. Rac GTPases regulate actin polymerization and extension of
      the leading edge, whereas Rho GTPases control myosin-based contraction of the
      trailing edge. Rac and Rho signaling are thought to crosstalk with one another,
      and previous research has focused on mutual inhibition of Rac and Rho signaling
      during chemotaxis. Indeed, polarization of neutrophils has been proposed to
      involve the activity of a negative feedback system where Rac activation at the
      front of the cell inhibits local Rho activation, and vice versa. Using primary
      human neutrophils and neutrophils derived from a Rac1/Rac2-null transgenic mouse
      model, we demonstrate here that Rac1 (and not Rac2) is essential for Rho and
      myosin activation at the trailing edge to regulate uropod function. We conclude
      that Rac plays both positive and negative roles in the organization of the
      Rhomyosin "backness" program, thereby promoting stable polarity in chemotaxing
      neutrophils.

PMID- 16809620
TI  - Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct
      binding to CD160 receptor expressed by endothelial cells.
AB  - HLA-G is a major histocompatibility complex class Ib molecule whose constitutive
      tissue distribution is restricted mainly to trophoblast cells at the maternal
      fetal interface during pregnancy. In this study, we demonstrated the ability of
      the soluble HLA-G1 (sHLA-G1) isoform to inhibit fibroblast growth factor-2 (FGF2)
      induced capillary-like tubule formation. Using a rabbit corneal
      neovascularization model, we further showed that sHLA-G1 inhibits FGF2-induced
      angiogenesis in vivo. We also demonstrated that sHLA-G1 induces endothelial cell
      apoptosis through binding to BY55/CD160, a glycosylphosphatidylinositolanchored
      receptor expressed by endothelial cells. Furthermore, we showed that the specific
      CL1-R2 anti-CD160 monoclonal antibody mimics sHLA-G1-mediated inhibition of
      endothelial cell tube formation and induction of apoptosis. Thus, the engagement
      of CD160 in endothelial cells may be essential for the inhibition of
      angiogenesis. sHLA-G1/CD160-mediated antiangiogenic property may participate in
      the vascular remodeling of maternal spiral arteries during pregnancy, and, given
      that we found that CD160 is strongly expressed in the vasculature of a murine
      tumor, it offers an attractive therapeutic target for preventing pathologic
      neovascularization.

PMID- 16809621
TI  - Gene loss and evolutionary rates following whole-genome duplication in teleost
      fishes.
AB  - Teleost fishes provide the first unambiguous support for ancient whole-genome
      duplication in an animal lineage. Studies in yeast or plants have shown that the
      effects of such duplications can be mediated by a complex pattern of gene
      retention and changes in evolutionary pressure. To explore such patterns in
      fishes, we have determined by phylogenetic analysis the evolutionary origin of
      675 Tetraodon duplicated genes assigned to chromosomes, using additional data
      from other species of actinopterygian fishes. The subset of genes, which was
      retained in double after the genome duplication, is enriched in development,
      signaling, behavior, and regulation functional categories. The evolutionary rate
      of duplicate fish genes appears to be determined by 3 forces: 1) fish proteins
      evolve faster than mammalian orthologs; 2) the genes kept in double after genome
      duplication represent the subset under strongest purifying selection; and 3)
      following duplication, there is an asymmetric acceleration of evolutionary rate
      in one of the paralogs. These results show that similar mechanisms are at work in
      fishes as in yeast or plants and provide a framework for future investigation of
      the consequences of duplication in fishes and other animals.

PMID- 16809622
TI  - Tracking down human contamination in ancient human teeth.
AB  - DNA contamination arising from the manipulation of ancient calcified tissue
      samples is a poorly understood, yet fundamental, problem that affects the
      reliability of ancient DNA (aDNA) studies. We have typed the mitochondrial DNA
      hypervariable region I of the only 6 people involved in the excavation, washing,
      and subsequent anthropological and genetic study of 23 Neolithic remains
      excavated from Granollers (Barcelona, Spain) and searched for their presence
      among the 572 clones generated during the aDNA analyses of teeth from these
      samples. Of the cloned sequences, 17.13% could be unambiguously identified as
      contaminants, with those derived from the people involved in the retrieval and
      washing of the remains present in higher frequencies than those of the
      anthropologist and genetic researchers. This finding confirms, for the first
      time, previous hypotheses that teeth samples are most susceptible to
      contamination at their initial excavation. More worrying, the cloned contaminant
      sequences exhibit substitutions that can be attributed to DNA damage after the
      contamination event, and we demonstrate that the level of such damage increases
      with time: contaminants that are >10 years old have approximately 5 times more
      damage than those that are recent. Furthermore, we demonstrate that in this data
      set, the damage rate of the old contaminant sequences is indistinguishable from
      that of the endogenous DNA sequences. As such, the commonly used argument that
      miscoding lesions observed among cloned aDNA sequences can be used to support
      data authenticity is misleading in scenarios where the presence of old
      contaminant sequences is possible. We argue therefore that the typing of those
      involved in the manipulation of the ancient human specimens is critical in order
      to ensure that generated results are accurate.

PMID- 16809623
TI  - Processed pseudogenes are more abundant in human and mouse X chromosomes than in
      autosomes.
AB  - Two different hypotheses have been proposed to explain the observation that some
      genomes contain more processed pseudogenes than others. One predicts that
      processed pseudogene abundance is inversely proportional to the substrate
      specificity of the reverse transcriptase that generates processed pseudogenes.
      The other predicts that the amount of processed pseudogenes found in genomes is
      proportional to the length of oogenesis. Here, we test the oogenesis hypothesis
      by analyzing the data from 6 studies that described the number of pseudogenes on
      different chromosomes of the human and/or mouse genomes. Our results show a
      significant overabundance of processed pseudogenes in the X chromosomes and a
      significant underrepresentation of processed pseudogenes in the Y chromosome of
      the human genome. These observations support the hypothesis that the number of
      processed pseudogenes is proportional to the length of oogenesis.

PMID- 16809624
TI  - Effects of load carrying on metabolic cost and hindlimb muscle dynamics in guinea
      fowl (Numida meleagris).
AB  - The goal of this study was to test whether the contractile patterns of two major
      hindlimb extensors of guinea fowl are altered by load-carrying exercise. We
      hypothesized that changes in contractile pattern, specifically a decrease in
      muscle shortening velocity or enhanced stretch activation, would result in a
      reduction in locomotor energy cost relative to the load carried. We also
      anticipated that changes in kinematics would reflect underlying changes in muscle
      strain. Oxygen consumption, muscle activation intensity, and fascicle strain rate
      were measured over a range of speeds while animals ran unloaded vs. when they
      carried a trunk load equal to 22% of their body mass. Our results showed that
      loading produced no significant (P > 0.05) changes in kinematic patterns at any
      speed. In vivo muscle contractile strain patterns in the iliotibialis lateralis
      pars postacetabularis and the medial head of the gastrocnemius showed a
      significant increase in active stretch early in stance (P < 0.01), but muscle
      fascicle shortening velocity was not significantly affected by load carrying. The
      rate of oxygen consumption increased by 17% (P < 0.01) during loaded conditions,
      equivalent to 77% of the relative increase in mass. Additionally, relative
      increases in EMG intensity (quantified as mean spike amplitude) indicated less
      than proportional recruitment, consistent with force enhancement via stretch
      activation, in the proximal iliotibialis lateralis pars postacetabularis;
      however, a greater than proportional increase in the medial gastrocnemius was
      observed. As a result, when averaged for the two muscles, EMG intensity increased
      in direct proportion to the fractional increase in load carried.

PMID- 16809625
TI  - Experimentally evolving exercise endurance: one step at a time.

PMID- 16809626
TI  - Can supraspinal/central fatigue explain the lesser muscle endurance of men
      compared with women?

PMID- 16809627
TI  - Training-induced adaptive plasticity in human somatosensory reflex pathways.
AB  - This paper reviews evidence supporting adaptive plasticity in muscle and
      cutaneous afferent reflex pathways induced by training and rehabilitative
      interventions. The perspective is advanced that the behavioral and functional
      relevance of any intervention and the reflex pathway under study should be
      considered when evaluating both adaptation and transfer. A cornerstone of this
      concept can be found in acute task-dependent reflex modulation. Because the
      nervous system allows the expression of a given reflex according to the motor
      task, an attempt to evaluate the training adaptation should also be evoked under
      the same conditions as training bearing in mind the functional role of the
      pathway under study. Within this framework, considerable evidence supports
      extensive adaptive plasticity in human muscle afferent pathways in the form of
      operant conditioning, strength training, skill training, and locomotor training
      or retraining. Directly comparable evidence for chronic adaptation in cutaneous
      reflex pathways is lacking. However, activity-dependent plasticity in cutaneous
      pathways is documented particularly in approaches to neurological rehabilitation.
      Overall, the adaptive range for human muscle afferent reflexes appears
      bidirectional (that is, increased or reduced amplitudes) and on the order of 25
      50%. The adaptive range for cutaneous pathways is currently uncertain.

PMID- 16809628
TI  - Systemic hypoxia and vasoconstrictor responsiveness in exercising human muscle.
AB  - Exercise blunts sympathetic alpha-adrenergic vasoconstriction (functional
      sympatholysis). We hypothesized that sympatholysis would be augmented during
      hypoxic exercise compared with exercise alone. Fourteen subjects were monitored
      with ECG and pulse oximetry. Brachial artery and antecubital vein catheters were
      placed in the nondominant (exercising) arm. Subjects breathed hypoxic gas to
      titrate arterial O2 saturation to 80% while remaining normocapnic via a rebreath
      system. Baseline and two 8-min bouts of rhythmic forearm exercise (10 and 20% of
      maximum) were performed during normoxia and hypoxia. Forearm blood flow, blood
      pressure, heart rate, minute ventilation, and end-tidal CO2 were measured at rest
      and during exercise. Vasoconstrictor responsiveness was determined by responses
      to intra-arterial tyramine during the final 3 min of rest and each exercise bout.
      Heart rate was higher during hypoxia (P < 0.01), whereas blood pressure was
      similar (P = 0.84). Hypoxic exercise potentiated minute ventilation compared with
      normoxic exercise (P < 0.01). Forearm blood flow was higher during hypoxia
      compared with normoxia at rest (85 +/- 9 vs. 66 +/- 7 ml/min), at 10% exercise
      (276 +/- 33 vs. 217 +/- 27 ml/min), and at 20% exercise (464 +/- 32 vs. 386 +/-
      28 ml/min; P < 0.01). Arterial epinephrine was higher during hypoxia (P < 0.01);
      however, venoarterial norepinephrine difference was similar between hypoxia and
      normoxia before (P = 0.47) and during tyramine administration (P = 0.14).
      Vasoconstriction to tyramine (%decrease from pretyramine values) was blunted in a
      dose-dependent manner with increasing exercise intensity (P < 0.01).
      Interestingly, vasoconstrictor responsiveness tended to be greater (P = 0.06) at
      rest (-37 +/- 6% vs. -33 +/- 6%), at 10% exercise (-27 +/- 5 vs. -22 +/- 4%), and
      at 20% exercise (-22 +/- 5 vs. -14 +/- 4%) between hypoxia and normoxia,
      respectively. Thus sympatholysis is not augmented by moderate hypoxia nor does it
      contribute to the increased blood flow during hypoxic exercise.

PMID- 16809629
TI  - Increased submaximal insulin-stimulated glucose uptake in mouse skeletal muscle
      after treadmill exercise.
AB  - The primary purpose of this study was to determine the effect of prior exercise
      on insulin-stimulated glucose uptake with physiological insulin in isolated
      muscles of mice. Male C57BL/6 mice completed a 60-min treadmill exercise protocol
      or were sedentary. Paired epitrochlearis, soleus, and extensor digitorum longus
      (EDL) muscles were incubated with [3H]-2-deoxyglucose without or with insulin (60
      microU/ml) to measure glucose uptake. Insulin-stimulated glucose uptake for
      paired muscles was calculated by subtracting glucose uptake without insulin from
      glucose uptake with insulin. Muscles from other mice were assessed for glycogen
      and AMPK Thr172 phosphorylation. Exercised vs. sedentary mice had decreased
      glycogen in epitrochlearis (48%, P < 0.001), soleus (51%, P < 0.001), and EDL
      (41%, P < 0.01) and increased AMPK Thr172 phosphorylation (P < 0.05) in
      epitrochlearis (1.7-fold), soleus (2.0-fold), and EDL (1.4-fold). Insulin
      independent glucose uptake was increased 30 min postexercise vs. sedentary in the
      epitrochlearis (1.2-fold, P < 0.001), soleus (1.4-fold, P < 0.05), and EDL (1.3
      fold, P < 0.01). Insulin-stimulated glucose uptake was increased (P < 0.05)
      approximately 85 min after exercise in the epitrochlearis (sedentary: 0.266 +/-
      0.045 micromol x g(-1) x 15 min(-1); exercised: 0.414 +/- 0.051) and soleus
      (sedentary: 0.102 +/- 0.049; exercised: 0.347 +/- 0.098) but not in the EDL. Akt
      Ser473 and Akt Thr308 phosphorylation for insulin-stimulated muscles did not
      differ in exercised vs. sedentary. These results demonstrate enhanced submaximal
      insulin-stimulated glucose uptake in the epitrochlearis and soleus of mice 85 min
      postexercise and suggest that it will be feasible to probe the mechanism of
      enhanced postexercise insulin sensitivity by using genetically modified mice.

PMID- 16809630
TI  - Feedback-controlled stimulation enhances human paralyzed muscle performance.
AB  - Chronically paralyzed muscle requires extensive training before it can deliver a
      therapeutic dose of repetitive stress to the musculoskeletal system.
      Neuromuscular electrical stimulation, under feedback control, may subvert the
      effects of fatigue, yielding more rapid and extensive adaptations to training.
      The purposes of this investigation were to 1) compare the effectiveness of torque
      feedback-controlled (FDBCK) electrical stimulation with classic open-loop
      constant-frequency (CONST) stimulation, and 2) ascertain which of three
      stimulation strategies best maintains soleus torque during repetitive
      stimulation. When torque declined by 10%, the FDBCK protocol modulated the base
      stimulation frequency in three ways: by a fixed increase, by a paired pulse
      (doublet) at the beginning of the stimulation train, and by a fixed decrease. The
      stimulation strategy that most effectively restored torque continued for
      successive contractions. This process repeated each time torque declined by 10%.
      In fresh muscle, FDBCK stimulation offered minimal advantage in maintaining peak
      torque or mean torque over CONST stimulation. As long-duration fatigue developed
      in subsequent bouts, FDBCK stimulation became most effective ( approximately 40%
      higher final normalized torque than CONST). The high-frequency strategy was
      selected approximately 90% of the time, supporting that excitation-contraction
      coupling compromise and not neuromuscular transmission failure contributed to
      fatigue of paralyzed muscle. Ideal stimulation strategies may vary according to
      the site of fatigue; this stimulation approach offered the advantage of online
      modulation of stimulation strategies in response to fatigue conditions. Based on
      stress-adaptation principles, FDBCK-controlled stimulation may enhance training
      effects in chronically paralyzed muscle.

PMID- 16809631
TI  - Contractile properties and myosin heavy chain composition of rat tongue retrusor
      musculature show changes in early adulthood after 19 days of artificial rearing.
AB  - Previously, we showed that artificial rearing using the "pup in a cup" model
      results in decreased tongue activity and caused some minor alterations in the
      tongue retrusor musculature. However, the artificial rearing time frame
      previously chosen was brief (11 days). The purpose of the present investigation
      was to extend the artificial rearing period from postnatal days 3 to 21 (P21) to
      determine whether significant alterations occur as a result of this reduced
      tongue use. Several changes in contractile properties due to the artificial
      rearing process were observed, which fully recovered by postnatal days 41 to 42
      (P41-2). These changes included a shorter twitch contraction time, shorter twitch
      half-relaxation time, and decreased fatigue resistance. Styloglossus muscle
      exhibited more neonatal myosin heavy chain (MHC) isoform at P21 for the
      artificially reared (AR) group. Changes that were persistent at P41-2 were also
      observed. Maximum tetanic tension was lower for the AR group at P21 and P41-2
      compared with their dam-reared counterparts. Twitch tension was also lower by P41
      2 in the AR group. At P41-2, the AR group exhibited an increase in MHC IIa and a
      decrease in MHC IIb for the styloglossus muscle. In addition, the AR group
      exhibited a decreased MHC IIb for the long head of the biceps brachii at P41-2.
      Our results are similar to other models of hindlimb immobilization and
      suspension. By extending our artificial rearing period, this reduced tongue
      activity induced acute changes and alterations in the tongue retrusor musculature
      that persisted into early adulthood.

PMID- 16809632
TI  - Predicting non-completion of treatment for latent tuberculous infection: a
      prospective survey.
AB  - Treatment of latent tuberculosis (TB) infection (LTBI) is essential for the
      elimination of TB in the United States, but treatment is often not completed.
      Little is known about patients' reasons for not completing treatment. We
      hypothesized that certain health beliefs, lifestyle, and clinic- and regimen
      related barriers to provision of care could predict non-completion of LTBI
      treatment. METHODS: We administered a survey in English, Chinese, or Spanish to
      patients with LTBI at the first TB clinic visit. Using chi(2) and logistic
      regression analysis, we assessed demographics, TB risk factors, and survey
      responses as predictors of non-completion of 6 mo of isoniazid. RESULTS: 217
      patients, 90% foreign-born, completed the survey, and 28.6% of which finished at
      least 6 mo of isoniazid under usual clinic conditions. Multivariate analysis
      identified two independent predictors of non-completion: low risk perception of
      progressing to active TB without LTBI treatment (odds ratio [OR], 0.31 [0.13
      0.72], 95% confidence interval [CI]), p = 0.007, accounting for 20% of non
      completers, and not wanting venipuncture (OR, 0.43 [0.22-0.85], 95% CI), p =
      0.015, accounting for 37% of non-completers. Another 18% shared both predictors;
      thus these two predictors accounted for 75% of non-completers in total.
      CONCLUSIONS: Patients assess LTBI treatment risks and inconveniences relative to
      low perceived benefits at treatment outset. Predictors of LTBI treatment non
      completion are identifiable at the first visit. Targeting TB high-risk
      individuals, minimizing inconveniences, further education, and use of diagnostic
      tests with improved specificity for TB may address these concerns.

PMID- 16809633
TI  - Incidence and prevalence of idiopathic pulmonary fibrosis.
AB  - RATIONALE: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease
      of unknown etiology; its epidemiology in the United States has not been well
      characterized. OBJECTIVE: To estimate the annual incidence and prevalence of
      idiopathic pulmonary fibrosis in the United States. METHODS: Retrospective cohort
      design utilizing a large health care claims database spanning the period January
      1996 through December 2000. MEASUREMENTS AND MAIN RESULTS: Persons with
      idiopathic pulmonary fibrosis were identified based on diagnosis and procedure
      codes. Using broad case-finding criteria, prevalence was estimated to range from
      4.0 per 100,000 persons aged 18 to 34 yr to 227.2 per 100,000 among those 75 yr
      or older; annual incidence was estimated to range from 1.2 to 76.4 per 100,000.
      Using narrow case-finding criteria, prevalence ranged from 0.8 to 64.7 per
      100,000 persons; comparable figures for incidence were 0.4 to 27.1 per 100,000
      persons. Extrapolating these rates to the overall United States' population,
      prevalence was estimated to be 42.7 per 100,000 (incidence, 16.3 per 100,000)
      using broad criteria; with narrow criteria, prevalence was estimated to be 14.0
      per 100,000 (incidence, 6.8 per 100,000). CONCLUSIONS: Our results suggest that
      idiopathic pulmonary fibrosis is probably more common in the United States than
      previously reported.

PMID- 16809634
TI  - Importin 13 regulates nuclear import of the glucocorticoid receptor in airway
      epithelial cells.
AB  - Antiinflammatory effects of glucocorticoids are critical to treatment of airway
      inflammation in such common disorders as asthma. There is considerable variation
      in responsiveness to glucocorticoid, and prolonged exposure can result in
      glucocorticoid resistance. We cloned LGL2, a glucocorticoid-inducible gene in
      fetal rat lung. We described the characterization of lgl2 as a nuclear transport
      protein, classified as importin 13 (IPO13), and demonstrated developmental
      regulation of IPO13 nucleocytoplasmic shuttling. We now report on the
      identification of the glucocorticoid receptor (GR) as a cargo substrate for
      IPO13. Binding of GR and IPO13 was demonstrated by GR-GST pulldown and
      coimmunoprecipitation. To investigate the role of IPO13 in modulating GR
      signaling in the lung, we studied IPO13-regulated GR transport in airway
      epithelial cells. Small interfering RNAs that inhibited IPO13 synthesis prevented
      nuclear translocation of GR. Silencing of IPO13 also abrogated the ability of
      cortisol to inhibit synthesis of the inflammatory cytokine IL-8 after stimulation
      with TNF-alpha. Our findings support a role for IPO13 in promoting nuclear
      occupancy of GR in a way that strongly potentiates the antiinflammatory effects
      of glucocorticoids. We speculate that variation in cellular levels of IPO13 and
      intracellular IPO13 shuttling rates may contribute to glucocorticoid resistance.

PMID- 16809635
TI  - Identification of novel lung genes in bronchial epithelium by serial analysis of
      gene expression.
AB  - A description of the transcriptome of human bronchial epithelium should provide a
      basis for studying lung diseases, including cancer. We have deduced global gene
      expression profiles of bronchial epithelium and lung parenchyma, based on a vast
      dataset of nearly two million sequence tags from 21 serial analysis of gene
      expression (SAGE) libraries from individuals with a history of smoking. Our
      analysis suggests that the transcriptome of the bronchial epithelium is distinct
      from that of lung parenchyma and other tissue types. Moreover, our analysis has
      identified novel bronchial-enriched genes such as MS4A8B, and has demonstrated
      the use of SAGE for the discovery of novel transcript variants. Significantly,
      gene expression associated with ciliogenesis is evident in bronchial epithelium,
      and includes the expression of transcripts specifying axonemal proteins DNAI2,
      SPAG6, ASP, and FOXJ1 transcription factor. Moreover, expression of potential
      regulators of ciliogenesis such as MDAC1, NYD-SP29, ARMC3, and ARMC4 were also
      identified. This study represents a comprehensive delineation of the bronchial
      and parenchyma transcriptomes, identifying more than 20,000 known and
      hypothetical genes expressed in the human lung, and constitutes one of the
      largest human SAGE studies reported to date.

PMID- 16809636
TI  - Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with
      chronically inhaled endotoxin.
AB  - Endotoxin (LPS), a Gram-negative cell wall component, has potent proinflammatory
      properties. Acute LPS exposure causes airway inflammation; chronic exposure
      causes airway hyperreactivity and remodeling. IL-10 is an important
      antiinflammatory cytokine, which is decreased in patients with airway disease,
      such as asthma and cystic fibrosis. To examine the physiologic and therapeutic
      role of IL-10 in acute and chronic LPS-induced airway disease. Mice were exposed
      to aerosolized LPS once or daily for 4 wk. Endpoints were airway inflammation,
      airway reactivity to methacholine, extracellular matrix protein expression, and
      histologic analysis. IL-10-deficient mice developed significantly enhanced airway
      cellularity and remodeling when compared with C57BL/6 mice after chronic LPS
      inhalation. However they demonstrated less airway hyperreactivity associated with
      higher inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and lung
      lavage fluid nitrite levels. In a bone marrow transplantation model, the IL-10
      antiinflammatory effect was dependent on the hematopoietic but not on the
      parenchymal IL-10 expression. Induced epithelial human IL-10 expression protected
      from the LPS effects and led to decreased collagen production. IL-10 attenuates
      chronic LPS-induced airway inflammation and remodeling. Physiologically, the
      antiinflammatory effect of IL-10 is mediated by hematopoietic cells.
      Therapeutically, adenovirus-driven expression of human IL-10 in airway epithelia
      is sufficient for its protective effect on inflammation and remodeling. The role
      of IL-10 on airway hyperreactivity is complex: IL-10 deficiency protects against
      LPS-induced hyperreactivity, and is associated with higher eNOS, iNOS, and airway
      nitrate levels.

PMID- 16809637
TI  - CysLT1 receptor engagement induces activator protein-1- and NF-kappaB-dependent
      IL-8 expression.
AB  - Because cysteinyl-leukotrienes (cysLTs) are major protagonists in the
      pathophysiology of human asthma, and because neutrophils are involved in the more
      severe form of asthma, we studied the potential for leukotriene (LT) D(4) to
      induce synthesis of the chemokine IL-8 through activation of the CysLT1 receptor.
      We found LTD(4) to induce IL-8 gene expression in monocytic THP-1 cells and human
      dendritic cells with complete abrogation by selective CysLT1 antagonists. Human
      embryonic kidney-293 cells stably transfected with CysLT1 were used to better
      study the transcriptional regulation of the IL-8 promoter. Stimulation of the
      cells with graded concentrations of LTD(4) resulted in a time- and concentration
      dependent induction of IL-8 transcription and protein synthesis. Use of IL-8
      promoter mutants with substitutions in their NF-kappaB, activator protein (AP)-1,
      and NF-IL-6 binding elements revealed a requirement for NF-kappaB and AP-1, but
      not NF-IL-6, in LTD(4)-induced activation of the IL-8 promoter. Overexpression of
      dominant-negative IkappaBalpha inhibited the IL-8 transactivation induced by
      LTD(4). NF-kappaB DNA binding activity was induced by LTD(4), as determined by
      electrophoretic mobility shift assays, and could be supershifted by antibodies
      against p50 and p65. Supershift assays after LTD(4) stimulation also indicated
      the formation of a c-Jun/c-Fos complex. Moreover, our results demonstrate that
      LTD(4) upregulates the expression of c-fos and c-jun at the mRNA level. Our data
      show for the first time that LTD(4), via the CysLT1 receptor, can
      transcriptionally activate IL-8 production, with involvement of the transcription
      factors p50, p65, Fos, and Jun. These findings provide mechanistic and
      potentially therapeutic elements for modulation of the inflammatory component of
      asthma.

PMID- 16809638
TI  - Luminal amino acid sensing in the rat gastric mucosa.
AB  - Recent advancements in molecular biology in the field of taste perception in the
      oral cavity have raised the possibility for ingested nutrients to be "tasted" in
      the upper gastrointestinal tract. The purpose of this study was to identify the
      existence of a nutrient-sensing system by the vagus in the rat stomach. Afferent
      fibers of the gastric branch increased their firing rate solely with the
      intragastric application of the amino acid glutamate. Other amino acids failed to
      have the same effect. This response to glutamate was blocked by the depletion of
      serotonin (5-HT) and inhibition of serotonin receptor(3) (5-HT(3)) or nitric
      oxide (NO) synthase enzyme. Luminal perfusion with the local anesthesia lidocaine
      abolished the glutamate-evoked afferent activation. The afferent response was
      also mimicked by luminal perfusion with a NO donor, sodium nitroprusside. In
      addition, the NO donor-induced afferent activation was abolished by 5-HT(3)
      blockade as well. Altogether, these results strongly suggest the existence of a
      sensing system for glutamate in the rat gastric mucosa. Thus luminal glutamate
      would enhance the electrophysiological firing rate of afferent fibers from the
      vagus nerve of the stomach through the production of mucosal bioactive substances
      such as NO and 5-HT. Assuming there is a universal coexistence of free glutamate
      with dietary protein, a glutamate-sensing system in the stomach could contribute
      to the gastric phase of protein digestion.

PMID- 16809639
TI  - Taste receptors in the gastrointestinal tract III. Salty and sour taste: sensing
      of sodium and protons by the tongue.
AB  - Taste plays an essential role in food selection and consequently overall
      nutrition. Because salt taste is appetitive, humans ingest more salt than they
      need. Acids are the source of intrinsically aversive sour taste, but in mixtures
      with sweeteners they are consumed in large quantities. Recent results have
      provided fresh insights into transduction and sensory adaptation for the salty
      and sour taste modalities. The sodium-specific salt taste receptor is the
      epithelial sodium channel whereas a nonspecific salt taste receptor is a taste
      variant of the vanilloid receptor-1 nonselective cation channel, TRPV1. The
      proximate stimulus for sour taste is a decrease in the intracellular pH of a
      subset of acid-sensing taste cells, which serves as the input to separate
      transduction pathways for the phasic and tonic parts of the sour neural response.
      Adaptation to sour arises from the activation of the basolateral sodium-hydrogen
      exchanger isoform-1 by an increase in intracellular calcium that sustains the
      tonic phase of the sour taste response.

PMID- 16809640
TI  - Early detection of first-episode psychosis: the effect on 1-year outcome.
AB  - Early intervention is assumed to improve outcome in first-episode psychosis, but
      this has not been proven. OBJECTIVE: To study whether 1-year outcome will be
      better in a health care sector with early detection (ED) of psychosis compared
      with sectors with no early detection (no-ED). DESIGN: A quasi-experimental study
      with ED in 2 experimental sectors and no-ED in 2 control sectors. ED was achieved
      through low-threshold ED teams and information campaigns about psychosis for the
      public, schools, and primary health care providers. The ED and no-ED health care
      areas offered an equivalent assessment and treatment program during the first
      year. Two hundred and eighty-one patients were included; 88% were reassessed
      after 1 year. RESULTS: The ED-area patients (N = 141) had a median duration of
      untreated psychosis of 5 weeks at baseline compared with 16 weeks for patients in
      the no-ED area (N = 140). Positive and general symptoms, global assessment of
      functioning, quality of life, time to remission, and course of psychosis at 1
      year after the start of treatment were not different between ED and no-ED groups.
      Outcome was significantly better for the ED area for negative symptoms.
      CONCLUSIONS: The ED, no-ED differences at baseline become attenuated by 1 year
      but not the difference in negative symptoms, suggesting secondary prevention in
      this domain of psychopathology. However, this possibility requires further
      testing by follow-up and replication.

PMID- 16809641
TI  - The neo-adjuvant, surgical and adjuvant treatment of gastric adenocarcinoma.
      Current expert opinion derived from the Seventh World Congress on
      Gastrointestinal Cancer, Barcelona, 2005.

PMID- 16809642
TI  - Human monocyte-derived dendritic cells differentiated in the presence of IL-2
      produce proinflammatory cytokines and prime Th1 immune response.
AB  - Interleukin (IL)-2 plays an important role in the control of the immune
      responses, and it is released in a variety of tissues in response to inflammatory
      stimuli. As monocytes and mature dendritic cells (DCs) express CD25, the high
      affinity subunit of IL-2 receptor, we examined the effect of exogenous IL-2 on
      the in vitro generation and maturation of DCs from monocytes. Human monocyte
      derived DCs (MDDCs) were generated by culturing monocytes with granulocyte
      macrophage-colony stimulating factor (GM-CSF) and IL-4 in the presence or absence
      of IL-2. The cytokine was added at the beginning and after 5 days of culture. Our
      findings indicate that IL-2 does induce monocytes to differentiate into DCs with
      the same morphology and phenotype of that obtained in the presence of GM-CSF and
      IL-4 alone, but with some distinctive functional properties. DCs differentiated
      in the presence of IL-2 secreted significantly more IL-1beta, TNF-alpha, and IL
      12 p70 in response to lipopolysaccharide stimulation and induced allogeneic,
      naive T cells to release a significantly higher amount of interferon-gamma if
      compared with DCs obtained by culturing monocytes with GM-CSF and IL-4. These
      results indicate unrecognized effects of IL-2 on human MDDCs and suggest that an
      IL-2-rich environment during differentiation and maturation of DCs can modify
      their T helper cell-inducing properties.

PMID- 16809643
TI  - TLR4 gene dosage contributes to endotoxin-induced acute respiratory inflammation.
AB  - Toll-like receptor (TLR)4 is critical for endotoxin recognition and cellular
      responses. Using Tlr4 transgenic mice, we investigated the influence of Tlr4 gene
      dosage on acute respiratory response to endotoxin. Transgenic mice expressing
      three, six, or 30 copies of Tlr4, control, and Tlr4-deficient mice received
      intranasal administration of lipopolysaccharide (LPS; 10 ug), and the airway
      response was analyzed by plethysmography, lung histology, cell recruitment,
      cytokine and chemokine secretion and protein leakage into the bronchoalveolar
      space. We demonstrate that overexpression of Tlr4 augmented a LPS-induced
      bronchoconstrictive effect, as well as tumor necrosis factor and CXC chemokine
      ligand 1 (keratinocyte-derived chemokine) production. Neutrophil recruitment,
      microvascular and alveolar epithelial injury with protein leak in the airways,
      and damage of the lung microarchitecture were Tlr4 gene dose-dependently
      increased. Therefore, the TLR4 expression level determines the extent of acute
      pulmonary response to inhaled endotoxin, and TLR4 may thus be a valuable target
      for immunointervention in acute lung inflammation as a result of endotoxins.

PMID- 16809644
TI  - Development and function of naturally occurring CD4+CD25+ regulatory T cells.
AB  - The immune system has evolved numerous mechanisms of peripheral T cell
      immunoregulation, including a network of regulatory T (Treg) cells, to modulate
      and down-regulate immune responses at various times and locations and in various
      inflammatory circumstances. Amongst these, naturally occurring CD4(+)CD25(+) Treg
      cells (nTreg) represent a major lymphocyte population engaged in the dominant
      control of self-reactive T responses and maintaining tolerance in several models
      of autoimmunity. CD4(+)CD25(+) Treg cells differentiate in the normal thymus as a
      functionally distinct subpopulation of T cells bearing a broad T cell receptor
      repertoire, endowing these cells with the capacity to recognize a wide range of
      self and nonself antigen specificities. The generation of CD4(+)CD25(+) Treg
      cells in the immune system is genetically controlled, influenced by antigen
      recognition, and various signals, in particular, cytokines such as interleukin-2
      and transforming growth factor-beta1, control their activation, expansion, and
      suppressive effector activity. Functional abrogation of these cells in vivo or
      genetic defects that affect their development or function unequivocally promote
      the development of autoimmune and other inflammatory diseases in animals and
      humans. Recent progress has shed light on our understanding of the cellular and
      molecular basis of CD4(+)CD25(+) Treg cell-mediated immune regulation. This
      article discusses the relative contribution of CD4(+)CD25(+) nTreg cells in the
      induction of immunologic self-tolerance and provides a comprehensive overview of
      recent finding regarding the functional properties and effector mechanism of
      these cells, as revealed from various in vitro and in vivo models.

PMID- 16809645
TI  - Dendritic cell derived-exosomes: biology and clinical implementations.
AB  - Exosomes are nanometer-sized membrane vesicles invaginating from multivesicular
      bodies and secreted from different cell types. They represent an "in vitro"
      discovery, but vesicles with the hallmarks of exosomes are present in vivo in
      germinal centers and biological fluids. Their protein and lipid composition is
      unique and could account for their expanding functions such as eradication of
      obsolete proteins, antigen presentation, or "Trojan horses" for viruses or
      prions. The potential of dendritic cell-derived exosomes (Dex) as cell-free
      cancer vaccines is addressed in this review. Lessons learned from the pioneering
      clinical trials allowed reassessment of the priming capacities of Dex in
      preclinical models, optimizing clinical protocols, and delineating novel,
      biological features of Dex in cancer patients.

PMID- 16809646
TI  - Bringing geriatricians to the front lines: evaluation of a quality improvement
      intervention in primary care.
AB  - BACKGROUND: Frail elders often receive low-quality primary care, yet the optimal
      role of geriatricians in primary care settings remains uncertain. We evaluated
      the health utilization impacts of an innovative intervention emphasizing chronic
      disease self-management and physical activity promotion among frail elders in
      primary care. METHODS: The intervention was implemented within two primary care
      practices at a single clinic serving a large population of frail elders enrolled
      in a western Washington health plan. Subjects included older patients (age >or=65
      years) with disproportionate baseline outpatient service use who attended two on
      site visits with a geriatrician during which each received comprehensive
      assessment and a problem-solving intervention to enhance chronic disease self
      management and promote physical activity (N = 146). Our evaluation had a
      retrospective matched cohort design. Controls receiving primary care at other
      health plan clinics were matched 3:1 to intervention subjects by sex and a
      propensity score (N = 437), which was computed using demographic, clinical, and
      health care utilization factors that were predictive of attending the
      intervention. Among intervention subjects and controls following the
      intervention, we compared relative rates of hospitalization, outpatient and
      specialty visits, nursing home admission, mortality, and prescription of selected
      high-risk medications, as well as total health care costs. RESULTS: From March
      2002 to November 2003, the geriatrician evaluated 146 of 725 elderly subjects
      (20%) in the two primary care practices. During a mean follow-up of 1.3 years,
      intervention subjects had a reduced rate of hospitalization relative to matched
      controls (incidence rate ratio 0.57; 95% CI: 0.37 to 0.86; P < .01). Intervention
      and control subjects did not have significantly different rates of specialty
      visits, outpatient visits, nursing home admission, mortality, or high-risk
      prescriptions. Relative to matched controls during follow-up, total health care
      costs were 26.3% lower among intervention subjects (95% CI: 1.3%, 44.9%; P =
      .04). CONCLUSIONS: Outpatient geriatric interventions emphasizing collaboration
      between geriatricians and primary care physicians, chronic disease self
      management, and physical activity may reduce hospitalization risk and total
      health care costs among vulnerable elders.

PMID- 16809647
TI  - Does gel affect cytology or comfort in the screening papanicolaou smear?
AB  - PURPOSE: Current medical training recommends obtaining cervical cytological
      specimens without the use of lubricating gel. The purpose of this study was to
      determine whether water-soluble lubricant gel affects cytologic outcomes in the
      screening Papanicolaou smear and patient comfort during vaginal speculum
      examination. METHODS: The study was a randomized controlled trial performed at
      David Grant US Air Force Medical Center (Travis Air Force Base, CA). Participants
      were female patients at least 18 years old presenting for an annual Papanicolaou
      smear. Each patient, blinded to group assignment, consented to two consecutive
      Papanicolaou smears. The first Papanicolaou smear was performed without gel in
      all subjects as part of the "standard of care." Thirty control patients underwent
      a second examination with no gel, and 40 other patients had the second
      examination with gel. All patients rated the discomfort of each Papanicolaou
      smear on a numerical pain scale. Main outcome measures were cytologic
      discrepancies on standard glass slide samples and comfort differences regarding
      the use of gel lubrication. Fisher's exact test was used to interpret the effect
      of gel on cytology results. Student's t test was performed to compare the
      discomfort ratings for the second Papanicolaou smear in the GEL vs. the NO GEL
      groups. RESULTS: There was no statistically significant difference between the
      number of inadequate Papanicolaou smears (P = .50) nor in the discomfort level
      ratings in the GEL vs. the NO GEL groups (P = .69). CONCLUSION: Speculum gel
      lubrication does not affect cervical cytology during the traditional Papanicolaou
      smear, nor does it provide significant alteration of patient discomfort.

PMID- 16809648
TI  - Increasing rates of influenza vaccination during pregnancy: a multisite
      interventional study.
AB  - BACKGROUND: Pregnancy is a high-risk indication for influenza vaccination;
      however, rates of vaccination fall short of Centers for Disease Control and
      Prevention-recommended guidelines. METHODS: Brief educational sessions with
      family physicians and obstetricians were undertaken in the fall of 2002. Notes
      reading "Think Flu Vaccine" were placed on active obstetric charts during the
      study period. Charts were reviewed at the end of influenza season for
      documentation of discussion or administration of influenza vaccination. Charts
      for the same period during the previous 2 years were also reviewed for baseline.
      RESULTS: Baseline rates of vaccination or discussion averaged 1.5% over the 2000
      2002 influenza seasons. After intervention, the 2002-2003 rate of vaccination or
      discussion demonstrated an almost 15-fold increase to 21.9%. This was greater in
      family practices (3.2% to 44.9%) versus obstetric practices (1.2% to 19.4%), and
      in small (3.3% to 46.7%) versus large (1.1% to 16%) practices (all values were P
      < .001). CONCLUSIONS: Provider education with simple chart prompts seems an
      effective way to increase rates of physician discussion of influenza vaccination
      with pregnant women. The increased rates seen in this study across various
      practice settings also suggest that inclusion of influenza vaccination on
      standardized prenatal care flowsheets may achieve similar goals with less
      individualized effort and should be considered.

PMID- 16809649
TI  - A handheld computer smoking intervention tool and its effects on physician
      smoking cessation counseling.
AB  - OBJECTIVE: The objective of this study was to evaluate a handheld computer
      smoking cessation intervention tool designed to assist physicians in their
      smoking cessation counseling with patients. METHODS: This study used a pre/post
      survey design, with a 4-month trial period for the software. Study participants
      included 22 faculty and resident physicians from the University of Virginia.
      Paired samples t tests were used to assess mean differences in the 4 main
      subscales (physician behavior, attitudes, comfort related to counseling patients
      about smoking cessation, and knowledge). RESULTS: No statistically significant
      mean differences were found for physician behavior (mean increase = 0.44, P =
      .55) or physician attitude (mean increase = 0.44, P = .16). A statistically
      significant mean increase of 2.29 was observed for the physician comfort subscale
      (t = 3.87, df = 16, P = .001). Physicians indicated improved comfort in
      counseling patients about smoking cessation (P = .007) and improved comfort in
      using the Public Health Service Clinical Practice Guidelines (P = .012).
      CONCLUSION: Physician comfort level in counseling patients about smoking
      cessation can be improved through handheld computer software. When used in
      conjunction with other practice modifications, this tool has the potential to
      improve physician smoking cessation intervention practices.

PMID- 16809650
TI  - Mothers' comfort with screening questions about sensitive issues, including
      domestic violence.
AB  - PURPOSE: To assess patient ratings of comfort alone and in front of children with
      5 domestic violence (DV) screening questions designed with less graphic language
      compared with questions about other sensitive issues. METHODS: A sample of
      mothers (n = 200), including a small sample of Spanish-speaking women, were
      recruited from community locations. Mothers rated their perceptions of comfort
      for answering 13 sensitive issue screening questions (including sexual risk,
      substance abuse, depression, and DV questions). Logistic regression was performed
      to analyze participants' characteristics with respect to summary comfort scores.
      In addition, 40 mothers were asked to talk about their comfort in answering the
      DV questions. These interviews were audiotaped and analyzed. RESULTS: Mothers
      preferred to answer all questions alone. Comfort with answering the DV screening
      questions in front of their children was higher than comfort with sexual risk or
      depression questions and was similar to comfort with substance abuse questions.
      Latina mothers had more discomfort with the DV questions than other ethnicities.
      CONCLUSIONS: Although mothers were more comfortable with answering sensitive
      questions alone than in the presence of children, this may not be feasible in
      busy offices. General DV questions may be appropriate to ask in front of children
      as an initial screen.

PMID- 16809651
TI  - Variability of vaginal pH determination by patients and clinicians.
AB  - PURPOSE: Measurement of intravaginal pH provides a reasonable assessment of
      vaginal health but is fraught with the potential for several sampling errors. The
      purposes of the study were to determine the variability of self-sampled vaginal
      pH among women using an inexpensive swab-based pH test compared with a clinician
      obtained specimen, and variability of vaginal pH within 3 regions of the normal
      vagina. METHODS: In this cross-sectional study, women obtained a vaginal specimen
      using a cotton-tip applicator, transferred it to pH paper, and interpreted the
      results. A clinician also blindly interpreted these tests. Thereafter, a
      clinician obtained 3 swab specimens from the proximal, middle, and distal vagina
      for pH testing. Results were compared using Wilcoxon signed rank test, interclass
      correlation coefficients, Bland-Altman plots, and mixed-model analysis of
      variance. RESULTS: Interclass correlation coefficients were moderately high
      comparing subjects with clinician for the swab-based pH test (0.74). Subjects'
      swab pH values (4.5) were significantly lower than clinicians' pH values (4.7, P
      = .0001). Intravaginal pH did not vary between the 3 anatomic locations.
      CONCLUSIONS: Self-sampled intravaginal pH interpretations vary slightly compared
      with clinician-obtained specimens. Because swab pH sampling does not detect an
      intravaginal pH gradient in normal women, self-sampling technique may vary
      considerably without affecting outcomes. Our findings support self-sampling for
      vaginal pH before using over-the-counter products for presumed vaginitis.

PMID- 16809652
TI  - Nursing the adopted infant.
AB  - BACKGROUND: Breast feeding is commonly accepted as the preferred method of infant
      nutrition for various reasons, both nutritional and emotional. For some who have
      become parents by adoption, there is a strong desire to induce lactation for
      adoptive nursing. METHODS: Information regarding adoptive nursing was initially
      obtained for the author's personal experience from searching the internet and
      speaking with other adoptive mothers. The medical literature was also searched
      through OVID/MEDLINE using pertinent terms, including induced lactation, adoptive
      nursing, domperidone, and metoclopramide. RESULTS: Use of physiologic and
      pharmacologic methods can help an adoptive mother bring in a milk supply. The
      quantity may not be sufficient to entirely meet an infant's nutritional needs.
      However, for many the emotional benefits remain. There is some controversy
      surrounding the use of domperidone and metoclopramide for induced lactation.
      Herbals such as fenugreek have not been researched. Physicians can help their
      patients understand the current tools available to assist them with this unique
      endeavor.

PMID- 16809653
TI  - Peritoneal dialysis: a primary care perspective.
AB  - As the population of chronic kidney disease (CKD) and end-stage renal disease
      (ESRD) grows at an alarming rate, primary care physicians will increasingly be
      involved in the management of these patients. Early recognition of CKD and timely
      referral to a nephrologist when glomerular filtration rate approaches 30
      mL/min/1.73 m(2) is extremely important to improve ESRD outcome and appropriate
      selection of dialysis modality. Peritoneal dialysis (PD) remains a viable
      treatment option for ESRD patients. PD is less expensive dialysis modality and
      may provide a survival advantages over hemodialysis in first 2 to 4 years of
      treatment. Preserving residual renal function (RRF) is of paramount importance to
      prolong the survival outcomes in PD patients. Thus preservation of RRF is an
      important goal in the management of PD patients. Every effort should be made to
      avoid nephrotoxic drugs like aminoglycosides and nonsteroidal anti-inflammatory
      drugs, and limit the use of radiocontrast agents in PD patients with RRF.
      Judicious use of prophylactic antibiotics to prevent peritonitis would further
      help to reduce morbidity from PD. Protecting peritoneal membrane from long-term
      toxic and metabolic effects of the conventional glucose-based solutions is
      another objective to further improve PD outcome. Development of new, more
      biocompatible PD solutions holds promise for the future. One such solution,
      icodextrin, is now approved for use in the United States. Although extremely safe
      to use, it is associated with unique metabolic effects that may concern primary
      care physicians. They include false elevation of blood glucose, a reversible
      increase in serum alkaline phosphatase and a false decline in serum amylase.
      Monitoring of glycemia by assays that use glucose dehydrogenase pyrroloquinoline
      quinone enzymes should be avoided and serum amylase alone should not be relied on
      in diagnosing pancreatitis in patients on icodextrin.

PMID- 16809654
TI  - Patients' perceptions of interpersonal continuity of care.
AB  - PURPOSE: The health system shift from doctor-patient continuity of care to team
      based continuity may not match patients' preferences. This article reviews the
      existing medical literature regarding patients' perceptions of interpersonal
      continuity of care to determine which patients value interpersonal continuity and
      in what context. METHODS: A search of the ISI Web of Knowledge database from 1970
      to April 2005 and the MEDLINE database from 1966 through April 2005 was performed
      to find articles that elicited patients' preferences or value for continuity of
      care. Thirty six articles were used for this synthesis. RESULTS: Interpersonal
      continuity of care is important to a majority of patients, particularly those
      from vulnerable groups. Patients value the relationship with their physician,
      their physician's knowledge about them, and the ability to communicate their
      concerns. Over time, contact with a physician seems to lead to the development of
      trust and confidence. However, continuity of care is not valued by all patients
      or across all settings. CONCLUSIONS: Future research should continue to explore
      the importance of interpersonal continuity to patients. In particular, are there
      medical consequences when those whom desire continuity do not receive it?
      Clinicians should consider incorporating patients' preference for continuity into
      their office scheduling procedures.

PMID- 16809655
TI  - Maintenance of certification for family physicians (MC-FP) self assessment
      modules (SAMs): the first year.
AB  - INTRODUCTION: In 2000, the American Board of Medical Specialties adopted
      Maintenance of Certification (MOC) to replace intermittent, periodic
      recertification. MOC consists of 4 components: demonstration of professionalism
      (part I); commitment to life-long learning (part II); demonstration of cognitive
      expertise (part III); and evaluation of performance in practice (part IV). The
      American Board of Family Medicine (ABFM) implemented Maintenance of Certification
      for Family Physicians (MC-FP) in 2004, with its MC-FP part II self-assessment
      modules (SAMs) as the focus of the first year's activities. METHODS: The SAMs use
      materials and resources provided at the ABFM's website (www.theabfm.org). As of
      April 2005, approximately 7000 Diplomates had successfully completed SAMs in
      essential hypertension (N = 2351) and type 2 diabetes mellitus (N = 4648).
      Participants completed categorical modified Likert scale evaluations to receive
      continuing education credit, and many offered unstructured free-text comments
      regarding the clinical simulation component. These free-text comments were
      entered into the AnSWR qualitative analysis program from the Centers for Disease
      Control and Prevention. Text coding was performed by 2 authors (MDH, DJI). As no
      inferential analyses or comparisons were anticipated, the authors conducted no
      studies of inter-rater consistency. Results are reported as means (SD) and
      medians for continuous data, and as frequencies for count data. RESULTS: Likert
      scale ratings indicated generally favorable responses (predominantly 5 to 6 on a
      6-point scale) to the hypertension and diabetes SAMs. In addition, over half (ie,
      55% for hypertension and 54% for diabetes participants) of the respondents
      indicated that the experience would lead to changes in their practices.
      Navigation and system operation issues predominated in the free-text comments
      offered for the diabetes and hypertension simulations. CONCLUSION: The MC-FP SAMs
      received generally favorable ratings in the program's first year. The SAMs
      underwent a number of modifications and improvements during the first year,
      largely in response to feedback and suggestions from ABFM Diplomates.

PMID- 16809656
TI  - Changing practice patterns of family medicine graduates: a comparison of alumni
      surveys from 1998 to 2004.
AB  - BACKGROUND AND OBJECTIVE: The University of Missouri family medicine residency
      has 297 family physician graduates. We suspected that the practice patterns of
      graduates were changing. METHODS: All graduates of the residency were surveyed in
      1998, 2001, and 2004, asking about practice patterns. To characterize current
      practice characteristics and scope, we used the latest survey returned by each
      respondent. We analyzed data for persons who returned all 3 surveys to examine
      trends across surveys. RESULTS: Annual response rates ranged from 58% to 78%. Of
      graduates who responded to all 3 surveys, fewer graduates care for patients in
      the hospital (71.3%, 1998; 56.5%, 2004), practice obstetrics (40.7%, 1998; 23.2%,
      2004), or provide primary care for their patients in the emergency department
      (25.9%, 1998; 13.0%, 2004). Fewer recent graduates perform flexible sigmoidoscopy
      or exercise electrocardiograms. Graduates who are practicing obstetrics are more
      likely to be rural or to have graduated since 1994. Those performing flexible
      sigmoidoscopy are more likely to be male or to have graduated before 1994. The
      perceived need for more training in practice management is higher for more recent
      graduates (14.9% for 1975 to 1983 graduates; 31.9% for 1994 to 2003 graduates).
      CONCLUSIONS: Across the 3 surveys, there was a decline in the proportion of
      graduates of this family medicine residency program performing procedures,
      obstetrics, intensive care unit care, or hospital medicine. This study highlights
      how the practices of family medicine residency graduates may change over time.
      Data regarding residency graduate practice profiles may help predict the
      knowledge and skills residency graduates will need in their future practices and
      evaluate the impact of the Future of Family Medicine recommendations.

PMID- 16809657
TI  - Assessment for intimate partner violence: where do we stand?

PMID- 16809658
TI  - Goodbyes.
AB  - When my patients die, I am reminded always of all they taught me during our time
      together. Over the years, I have begun writing clinical obituaries to better
      celebrate their lives, to inform staff of their passing, and as a means to teach
      colleagues and students about a healthy way, as physicians, of dealing with
      patient deaths.

PMID- 16809659
TI  - Carvedilol suppresses intractable hiccups.
AB  - Carvedilol (6.25 mg, 4 times daily) relieved 2 years of constant hiccupping,
      marked tardive dyskinesia, compulsive self-induced vomiting, and feelings of
      hopelessness and low mood in a 59-year-old African-American man. He previously
      failed trials of ranitidine, chlorpromazine, promethazine, tegaserod,
      ondansetron, metoclopramide, pantoprazole, pyloric injections of botulinum toxin
      A, and a vagal nerve stimulator. At a 5-month follow-up, improvement was
      maintained; there had been several instances of rapid relapse on carvedilol
      discontinuation.

PMID- 16809660
TI  - Choroid plexus cysts.
AB  - BACKGROUND: Research shows that there is an association between choroid plexus
      cysts and aneuploidy. Family physicians treating prenatal patients should
      understand the management of this sonographic finding. OBJECTIVE: To determine
      the epidemiology, pathophysiology, and management of prenatal choroid plexus
      cysts. CASE REPORT: A 23-year-old patient, gravida 1, para 0, was seen at an
      inner city Family Medicine health center for prenatal care. A screening
      ultrasonogram performed at 16 weeks of gestation showed bilateral choroid plexus
      cysts approximately 5 mm in diameter. The patient declined amniocentesis.
      Maternal serum triple screen markers (maternal serum alpha-fetoprotein, human
      chorionic gonadotropin, and estriol) were all normal, as was the level II
      sonogram at 20 weeks and the fetal echocardiogram at 28 weeks. At birth the baby
      was found to be normal after a clinical assessment was performed. METHODS: A
      review of the literature using MEDLINE with the search strategy of choroid
      plexus, choroid plexus fetus/fetal, choroid plexus management, choroid plexus
      treatment, and choroid plexus epidemiology.

PMID- 16809661
TI  - Maternal shoe size and infant birth weight: correlation or fiction?
AB  - OBJECTIVE: To determine whether maternal prepregnancy shoe size can be used to
      reliably predict infant birth weight. METHOD: This is a cross-sectional study of
      111 consecutive patients admitted to the maternity care unit of a small community
      hospital. Data collected included prepregnancy height, maternal weight, maternal
      shoe size, maternal age, gravidity, parity, ethnicity, and method of delivery.
      Infant birth weight was recorded within the first 2 hours of life. RESULTS: There
      was no correlation between maternal shoe size and birth weight (r = 0.01; P =
      NS). There was no correlation between shoe size and birth weight when corrected
      for parity and ethnicity. CONCLUSION: There is no correlation between maternal
      shoe and infant birth weight. This anthropometric measure should not be used to
      estimate infant birth weight.

PMID- 16809662
TI  - Impact of religious attendance on life expectancy.

PMID- 16809665
TI  - Analysis on observational data that are of questionable validity.

PMID- 16809663
TI  - Religious attendance: more cost-effective than lipitor?

PMID- 16809666
TI  - Copy number variation: new insights in genome diversity.
AB  - DNA copy number variation has long been associated with specific chromosomal
      rearrangements and genomic disorders, but its ubiquity in mammalian genomes was
      not fully realized until recently. Although our understanding of the extent of
      this variation is still developing, it seems likely that, at least in humans,
      copy number variants (CNVs) account for a substantial amount of genetic
      variation. Since many CNVs include genes that result in differential levels of
      gene expression, CNVs may account for a significant proportion of normal
      phenotypic variation. Current efforts are directed toward a more comprehensive
      cataloging and characterization of CNVs that will provide the basis for
      determining how genomic diversity impacts biological function, evolution, and
      common human diseases.

PMID- 16809667
TI  - Genomic clusters, putative pathogen recognition molecules, and antimicrobial
      genes are induced by infection of C. elegans with M. nematophilum.
AB  - The interaction between the nematode Caenorhabditis elegans and a Gram-positive
      bacterial pathogen, Microbacterium nematophilum, provides a model for an innate
      immune response in nematodes. This pathogen adheres to the rectal and post-anal
      cuticle of the worm, causing slowed growth, constipation, and a defensive
      swelling response of rectal hypodermal cells. To explore the genomic responses
      that the worm activates after pathogenic attack we used microarray analysis of
      transcriptional changes induced after 6-h infection, comparing virulent with
      avirulent infection. We defined 89 genes with statistically significant
      expression changes of at least twofold, of which 68 were up-regulated and 21 were
      down-regulated. Among the former, those encoding C-type lectin domains were the
      most abundant class. Many of the 89 genes exhibit genomic clustering, and we
      identified one large cluster of 62 genes, of which most were induced in response
      to infection. We tested 41 of the induced genes for involvement in immunity using
      mutants or RNAi, finding that six of these are required for the swelling response
      and five are required more generally for defense. Our results indicate that C
      type lectins and other putative pathogen-recognition molecules are important for
      innate immune defense in C. elegans. We also found significant induction of genes
      encoding lysozymes, proteases, and defense-related proteins, as well as various
      domains of unknown function. The genes induced during infection by M.
      nematophilum appear largely distinct from genes induced by other pathogens,
      suggesting that C. elegans mounts pathogen-specific responses to infection.

PMID- 16809668
TI  - Comparative isoschizomer profiling of cytosine methylation: the HELP assay.
AB  - The distribution of cytosine methylation in 6.2 Mb of the mouse genome was tested
      using cohybridization of genomic representations from a methylation-sensitive
      restriction enzyme and its methylation-insensitive isoschizomer. This assay,
      termed HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR), allows
      both intragenomic profiling and intergenomic comparisons of cytosine methylation.
      The intragenomic profile shows most of the genome to be contiguous methylated
      sequence with occasional clusters of hypomethylated loci, usually but not
      exclusively at promoters and CpG islands. Intergenomic comparison found marked
      differences in cytosine methylation between spermatogenic and brain cells,
      identifying 223 new candidate tissue-specific differentially methylated regions
      (T-DMRs). Bisulfite pyrosequencing confirmed the four candidates tested to be T
      DMRs, while quantitative RT-PCR for two genes with T-DMRs located at their
      promoters showed the HELP data to be correlated with gene activity at these loci.
      The HELP assay is robust, quantitative, and accurate and is providing new
      insights into the distribution and dynamic nature of cytosine methylation in the
      genome.

PMID- 16809669
TI  - Heterozygous carriers of Nijmegen Breakage Syndrome have a distinct gene
      expression phenotype.
AB  - Autosomal recessive diseases are those that require mutations in both alleles to
      exhibit the disorder. Although most recessive conditions are rare, heterozygous
      carriers of recessive mutations are quite common. In this study, we show that
      carriers of Nijmegen Breakage Syndrome (NBS) have a distinct gene expression
      phenotype that differs from that of noncarriers and also from that of carriers of
      a similar syndrome, Ataxia Telangiectasia (AT). We found 520 genes whose
      expression levels differ significantly (P < or = 0.001) between NBS carriers and
      controls. By linear discriminant analysis, we found a combination of 16 genes
      that allows 100% correct classification of individuals as either NBS carriers or
      noncarriers in a training set with 25 individuals, and in a test set with 52
      individuals. When applied to AT carriers, the discriminant function misclassified
      only one out of 18 AT carriers as an NBS carrier. Our result shows that NBS
      carriers have a specific gene expression phenotype. It suggests that heterozygous
      mutations can contribute significantly to natural variation in gene expression.
      This has implications for the role that heterozygosity for recessive diseases
      plays in the overall genetic architecture of complex human traits and diseases.

PMID- 16809670
TI  - RNA expression profiling at the single molecule level.
AB  - We developed a microarray platform for PCR amplification-independent expression
      profiling of minute samples. A novel scanning system combined with specialized
      biochips enables detection down to individual fluorescent oligonucleotide
      molecules specifically hybridized to their complementary sequence over the entire
      biochip surface of cm2 size. A detection limit of 1.3 fM target oligonucleotide
      concentration--corresponding to only 39,000 molecules in the sample solution--and
      a dynamic range of 4.7 orders of magnitude have been achieved. The applicability
      of the system to PCR amplification-independent gene-expression profiling of
      minute samples was demonstrated by complex hybridization of cDNA derived from the
      equivalent of only 10(4) cells, which matches results obtained in ensemble
      studies on large samples. By counting each hybridized molecule on the microarray,
      the method is insusceptible to gene-specific variations of the labeling, thereby
      representing a principle advance to conventional ensemble-based microarray
      analysis.

PMID- 16809671
TI  - Extensive low-affinity transcriptional interactions in the yeast genome.
AB  - Major experimental and computational efforts are targeted at the characterization
      of transcriptional networks on a genomic scale. The ultimate goal of many of
      these studies is to construct networks associating transcription factors with
      genes via well-defined binding sites. Weaker regulatory interactions other than
      those occurring at high-affinity binding sites are largely ignored and are not
      well understood. Here I show that low-affinity interactions are abundant in vivo
      and quantifiable from current high-throughput ChIP experiments. I develop
      algorithms that predict DNA-binding energies from sequences and ChIP data across
      a wide dynamic range of affinities and use them to reveal widespread
      functionality of low-affinity transcription factor binding. Evolutionary analysis
      suggests that binding energies of many transcription factors are conserved even
      in promoters lacking classical binding sites. Gene expression analysis shows that
      such promoters can generate significant expression. I estimate that while only a
      small percentage of the genome is strongly regulated by a typical transcription
      factor, up to an order of magnitude more may be involved in weaker interactions.
      Low-affinity transcription factor-DNA interaction may therefore be important both
      evolutionarily and functionally.

PMID- 16809672
TI  - Relaxation of selective constraint on dog mitochondrial DNA following
      domestication.
AB  - The domestication of dogs caused a dramatic change in their way of life compared
      with that of their ancestor, the gray wolf. We hypothesize that this new life
      style changed the selective forces that acted upon the species, which in turn had
      an effect on the dog's genome. We sequenced the complete mitochondrial DNA genome
      in 14 dogs, six wolves, and three coyotes. Here we show that dogs have
      accumulated nonsynonymous changes in mitochondrial genes at a faster rate than
      wolves, leading to elevated levels of variation in their proteins. This suggests
      that a major consequence of domestication in dogs was a general relaxation of
      selective constraint on their mitochondrial genome. If this change also affected
      other parts of the dog genome, it could have facilitated the generation of novel
      functional genetic diversity. This diversity could thus have contributed raw
      material upon which artificial selection has shaped modern breeds and may
      therefore be an important source of the extreme phenotypic variation present in
      modern-day dogs.

PMID- 16809674
TI  - Can patients assess the quality of health care?

PMID- 16809675
TI  - Antipyretic drugs for children.

PMID- 16809676
TI  - Psychological interventions for treatment of adult sex offenders.

PMID- 16809679
TI  - Publicity will highlight problem of obstetric fistula.

PMID- 16809680
TI  - NICE removes beta blockers as first line treatment for hypertension.

PMID- 16809684
TI  - US doctors lobby for end to torture of terrorism suspects.

PMID- 16809687
TI  - UN report calls for governments to intensify fight against drug abuse.

PMID- 16809689
TI  - Faster delivery of drugs to heart attack patients cuts mortality.

PMID- 16809690
TI  - Drug company chief urges faster introduction of new vaccines in poor nations.

PMID- 16809691
TI  - US doctors' incomes are falling, new survey finds.

PMID- 16809693
TI  - Direct to consumer medical tests are offered in United States.

PMID- 16809695
TI  - Too close for comfort?

PMID- 16809697
TI  - BMA Annual Representative Meeting: doctors recommend a "traffic light" system to
      signal nutritional content of food products.

PMID- 16809701
TI  - Only specialists should diagnose Parkinson's disease.

PMID- 16809702
TI  - Inhaled insulin no longer recommende as routine diabetes treatment.

PMID- 16809705
TI  - Meeting hears of health consequences of rape and violence in war zones.

PMID- 16809706
TI  - International consumer group slates drug companies' marketing practices.

PMID- 16809708
TI  - Escalating costs and falling receipts spell trouble.

PMID- 16809709
TI  - The healthy adherer and the placebo effect.

PMID- 16809710
TI  - Hip fracture.

PMID- 16809711
TI  - A patient's journey: living with breast cancer.

PMID- 16809712
TI  - Oxygen and inhalers.

PMID- 16809714
TI  - Patients should have to opt out of national electronic care records: FOR.

PMID- 16809715
TI  - Patients should have to opt out of national electronic care records: what's all
      the fuss about?

PMID- 16809716
TI  - The great medicines scandal: next steps?

PMID- 16809717
TI  - The great medicines scandal: access is not just about cost.

PMID- 16809719
TI  - Care is needed before single test results are combined.

PMID- 16809718
TI  - Obesity association clarifies definitions of obesity and links with drug firms.

PMID- 16809720
TI  - Censorship of medical journals.

PMID- 16809721
TI  - We still need artesunate monotherapy.

PMID- 16809724
TI  - Statin guidelines should give best statin.

PMID- 16809725
TI  - Rethinking risk-benefit assessment for phase I cancer trials.

PMID- 16809726
TI  - Progression-free survival rate as primary end point for phase II cancer clinical
      trials: application to mesothelioma--The EORTC Lung Cancer Group.
AB  - PURPOSE: Phase II cancer clinical trials play a key role in the development of
      new drugs. These trials should be designed to accurately determine if the drug
      should be abandoned or if it is sufficiently promising for further investigation
      in phase III trials. With new cytostatic agents or when the response assessment
      is difficult, using the progression-free survival rate (PFSR) at a fixed time
      point, such as 3, 4, 5, or 6 months, instead of the response rate (RR) as the
      primary end point is an alternative approach. To design future phase II trials,
      reference values for PFSRs that correspond to drugs with insufficient (P0) and
      sufficient (P1) clinical activity (CA) are necessary. This article provides these
      values in mesothelioma. MATERIALS AND METHODS: The European Organisation for
      Research and Treatment of Cancer database registered ten closed mesothelioma
      trials (nine phase II trials and one phase III trial) with 523 total patients.
      Trials were grouped into three categories according to the published RR:
      significant (n = 259), moderate (n = 142), and insufficient (n = 122) CA.
      RESULTS: The PFSRs at 3, 4, 5, and 6 months, respectively, were as follows: 72%,
      67%, 51%, and 43% in the group with significant CA; 59%, 51%, 42%, and 35% with
      moderate CA; and 52%, 40%, 34%, and 28% with insufficient CA. CONCLUSION: These
      values may be used to define relevant P0 and P1 values in future phase II
      mesothelioma trials that use PFSR as the primary end point.

PMID- 16809727
TI  - HER2 testing by local, central, and reference laboratories in specimens from the
      North Central Cancer Treatment Group N9831 intergroup adjuvant trial.
AB  - PURPOSE: To evaluate concordance between local and central laboratory HER2
      testing results in patients from the North Central Cancer Treatment Group (NCCTG)
      N9831 adjuvant trial of trastuzumab. PATIENTS AND METHODS: NCCTG N9831 is a
      randomized, phase III clinical trial comparing three drug regimens:
      doxorubicin/cyclophosphamide followed by paclitaxel with trastuzumab added
      concurrently, sequentially, or not at all as adjuvant therapy for women with HER2
      positive resected breast cancer. Originally, patients were eligible if their
      tumors were HER2 positive by either local laboratory immunohistochemistry (IHC)
      or fluorescence in situ hybridization (FISH). A protocol modification in 2002
      made central laboratory testing mandatory, with additional testing of discordant
      cases conducted by a reference laboratory. Concordance between local and central
      laboratory, and level of agreement between central and reference laboratory HER2
      findings in discordant cases were examined. RESULTS: HER2 positivity was
      confirmed in 85.8% of 2,535 patients registered since March 2002. When local and
      central evaluation used the same methodology, concordance was 88.1% for FISH and
      81.6% for a diagnostic test for presence of the HER2 protein. Among discordant
      cases examined at the reference laboratory, there was 94.3% agreement for IHC (0,
      1+, 2+) and 95.2% agreement for FISH (not gene amplified). CONCLUSION: There was
      a high degree of discordance between local and central testing for IHC and FISH,
      but a high degree of agreement between central and reference laboratories. These
      findings support the importance of using high-volume, experienced laboratories
      for HER2 testing to improve the process of selecting patients likely to benefit
      from trastuzumab therapy.

PMID- 16809728
TI  - Novel prognostic immunohistochemical biomarker panel for estrogen receptor
      positive breast cancer.
AB  - PURPOSE: Patients with breast cancer experience progression and respond to
      treatment in diverse ways, but prognostic and predictive tools for the oncologist
      are limited. We have used gene expression data to guide the production of
      hundreds of novel antibody reagents to discover novel diagnostic tools for
      stratifying carcinoma patients. PATIENTS AND METHODS: One hundred forty novel and
      23 commercial antisera, selected on their ability to differentially stain tumor
      samples, were used to stain paraffin blocks from a retrospective breast cancer
      cohort. Cox proportional hazards and regression tree analysis identified minimal
      panels of reagents able to predict risk of recurrence. We tested the prognostic
      association of these prospectively defined algorithms in two independent cohorts.
      RESULTS: In both validation cohorts, the Kaplan-Meier estimates of recurrence
      confirmed that both the Cox model using five reagents (p53, NDRG1, CEACAM5,
      SLC7A5, and HTF9C) and the regression tree model using six reagents (p53, PR,
      Ki67, NAT1, SLC7A5, and HTF9C) distinguished estrogen receptor (ER)-positive
      patients with poor outcomes. The Cox model was superior and distinguished
      patients with poor outcomes from patients with good or moderate outcomes with a
      hazard ratio of 2.21 (P = .0008) in validation cohort 1 and 1.88 (P = .004) in
      cohort 2. In multivariable analysis, the calculated risk of recurrence was
      independent of stage, grade, and lymph node status. A model proposed for ER
      negative patients failed validation in the independent cohorts. CONCLUSION: A
      panel of five antibodies can significantly improve on traditional prognosticators
      in predicting outcome for ER-positive breast cancer patients.

PMID- 16809729
TI  - Phase II trial of alfimeprase, a novel-acting fibrin degradation agent, for
      occluded central venous access devices.
AB  - PURPOSE: Alfimeprase is a recombinantly produced, genetically modified variant of
      the metalloproteinase, fibrolase. Alfimeprase proteolytically cleaves fibrin,
      independent of plasminogen activation to plasmin, and directly dissolves thrombi.
      Based on the direct fibrin degradation effect of alfimeprase, rapid activity in
      patients with occluded central venous access devices (CVADs) was hypothesized.
      PATIENTS AND METHODS: We performed a phase II, randomized, double-blind, active
      control, multicenter, dose-ranging study to compare the safety and efficacy of
      one or two instillations of three intraluminal doses of alfimeprase (0.3, 1.0,
      and 3.0 mg) and alteplase 2.0 mg in re-establishing patency to occluded CVADs in
      55 adult patients. RESULTS: All three alfimeprase doses were more successful than
      alteplase during the first 15 and 30 minutes of treatment. The alfimeprase 3.0-mg
      dose resulted in 40%, 50%, and 60% patency restoration rates at 5, 15, and 30
      minutes, respectively, compared with 0%, 0%, and 23% for alteplase. The
      difference at 15 minutes was highly significant (P = .0075). Alfimeprase 3.0 mg
      produced the highest patency rate at 120 minutes after the first (60%) and second
      (80%) doses. No major hemorrhagic or embolic events were reported. CONCLUSION: A
      single 1- or 3-mg dose of alfimeprase has the potential to restore function to
      occluded CVADs rapidly and safely, and to facilitate on-time infusion of vital
      therapies.

PMID- 16809730
TI  - The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics
      of irinotecan in patients with metastatic colorectal cancer.
AB  - PURPOSE: UGT1A1*28 polymorphism has been associated with decreased
      glucuronidation of SN38, the active metabolite of irinotecan. This could increase
      toxicity with this agent. PATIENTS AND METHODS: In a prospective study, 250
      metastatic colorectal cancer patients were treated with irinotecan, fluorouracil,
      and leucovorin as first-line treatment. UGT1A1*28 polymorphism was investigated
      with respect to the distribution of hematologic and nonhematologic toxicity,
      objective response rate, and survival. Pharmacokinetics was investigated in a
      subgroup of patients (71 of 250) who had been analyzed with respect to toxicity
      and efficacy. RESULTS: UGT1A1*28 polymorphism was associated with a higher risk
      of grade 3 to 4 hematologic toxicity (odds ratio [OR], 8.63; 95% CI, 1.31 to
      56.55), which was only relevant for the first cycle, and was not seen throughout
      the whole treatment period for patients with both variant alleles TA7/TA7
      compared with wild-type TA6/TA6. The response rate was also higher in TA7/TA7
      patients (OR, 0.32; 95% CI, 0.12 to 0.86) compared with TA6/TA6. A nonsignificant
      survival advantage was observed for TA7/TA7 when compared with TA6/TA6 patients
      (hazard ratio, 0.81; 95% CI, 0.45 to 1.44). Higher response rates were explained
      by a different pharmacokinetics with higher biliary index [irinotecan area under
      the curve (AUC)x(SN38 AUC/SN38G AUC)] and lower glucuronidation ratio (SN38G
      AUC/SN38 AUC) associated with the TA7/TA7 genotype and a higher response rate,
      indicating that the polymorphism is functionally relevant. CONCLUSION: The
      results indicate that UGT1A1*28 polymorphism is of some relevance to toxicity;
      however, it is less important than discussed in previous smaller trials. In
      particular, the possibility of a dose reduction for irinotecan in patients with a
      UGT1A1*28 polymorphism is not supported by the result of this analysis.

PMID- 16809731
TI  - Phase II study of erlotinib in patients with advanced biliary cancer.
AB  - PURPOSE: Epidermal growth factor receptor/human epidermal growth factor receptor
      1 and ligand expression is common in biliary cancers (BILI) and may be associated
      with worse outcome. The primary objective of this study was to determine the
      proportion of patients with advanced BILI who were progression-free at 6 months.
      METHODS: Patients with either unresectable or metastatic disease were studied.
      Only one prior systemic or locoregional therapy was allowed. Erlotinib was
      administered continuously at a dose of 150 mg per day orally. RESULTS: Forty-two
      patients with BILI were enrolled. The median age was 67 years (range, 33 to 82
      years). Fifty-two percent of patients had Eastern Cooperative Oncology Group
      performance status of 1. Fifty-seven percent of patients had received prior
      chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in
      tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the
      patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three
      patients had partial response by Response Evaluation Criteria in Solid Tumors
      Group classification of duration 4, 4, and 14 months, respectively. All
      responding patients had mild (grade 1/2) skin rash and two patients had positive
      tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose
      reductions of erlotinib due to grade 2/3 skin rash. CONCLUSION: Results suggest a
      therapeutic benefit for EGFR blockade with erlotinib in patients with biliary
      cancer. Additional studies with erlotinib as a single agent and in combination
      with other targeted agents are warranted in this disease.

PMID- 16809732
TI  - Phase I trial of intravesical docetaxel in the management of superficial bladder
      cancer refractory to standard intravesical therapy.
AB  - PURPOSE: Up to 50% of patients treated with intravesical agents for superficial
      bladder cancer will experience recurrence. Response rates to second-line
      intravesical therapies range from 20% to 40%. For these high-risk patients, novel
      agents are necessary to prevent recurrence. Docetaxel is a microtubule
      depolymerization inhibitor with unique physiochemical properties, making it an
      excellent candidate for investigation as an intravesical agent. PATIENTS AND
      METHODS: This phase I trial included patients with recurrent Ta, T1, and Tis
      transitional cell carcinoma who experienced treatment failure with at least one
      prior intravesical treatment. Docetaxel was administered as six weekly
      instillations at a starting dose of 5 mg, with a dose-escalation model used until
      a maximum tolerated dose (MTD) was achieved. Primary end points were dose
      limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with
      biopsy, cytology, and computed tomography imaging. RESULTS: Eighteen patients
      (100%) completed the trial, and the distribution of stages included six patients
      with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred
      in 108 infusions, and no patient had systemic absorption of docetaxel. Eight
      (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the
      most common. Ten (56%) of 18 patients had no evidence of disease at their post
      treatment cystoscopy and biopsy. None of the patients who experienced relapse had
      disease progression. CONCLUSION: Intravesical docetaxel exhibited minimal
      toxicity and no systemic absorption in the first human intravesical clinical
      trial. This suggests that docetaxel is a safe agent for further evaluation of
      efficacy in a phase II trial.

PMID- 16809733
TI  - Molecular load of pathologically occult metastases in pelvic lymph nodes is an
      independent prognostic marker of biochemical failure after localized prostate
      cancer treatment.
AB  - PURPOSE: Thirty percent of patients treated with curative intent for localized
      prostate cancer (PC) experience biochemical recurrence (BCR) with rising serum
      prostate-specific antigen (sPSA), and of these, approximately 50% succumb to
      progressive disease. More discriminatory staging procedures are needed to
      identify occult micrometastases that spawn BCR. PATIENTS AND METHODS: PSA mRNA
      copies in pathologically normal pelvic lymph nodes (N0-PLN) from 341 localized PC
      patients were quantified by real-time reverse-transcriptase polymerase chain
      reaction. Based on comparisons with normal lymph nodes and PLN with metastases
      and on normalization to 5 x 10(6) glyceraldehyde-3'-phosphate dehydrogenase mRNA
      copies, normalized PSA copies (PSA-N) and a threshold of PSA-N 100 or more were
      selected for continuous and categorical multivariate analyses of biochemical
      failure-free survival (BFFS) compared with established risk factors. RESULTS: At
      median follow-up of 4 years, the BFFS of patients with PSA-N 100 or more versus
      PSA-N less than 100 was 55% and 77% (P = .0002), respectively. The effect was
      greatest for sPSA greater than 20 ng/mL, 25% versus 60% (P = .014), Gleason score
      8 or higher, 21% versus 66% (P = .0002), stage T3c, 18% versus 64% (P = .001),
      and high-risk group (50% v 72%; P = .05). By continuous analysis PSA-N was an
      independent prognostic marker for BCR (P = .049) with a hazard ratio of 1.25 (95%
      CI, 1.001 to 1.57). By categorical analysis, PSA-N 100 or more was an independent
      variable (P = .021) with a relative risk of 1.98 (95% CI, 1.11 to 3.55) for BCR
      compared with PSA-N less than 100. CONCLUSION: PSA-N 100 or more is a new,
      independent molecular staging criterion for localized PC that identifies high
      risk group patients with clinically relevant occult micrometastases in N0-PLN,
      who may benefit from additional therapy to prevent BCR.

PMID- 16809734
TI  - Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T
      (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate
      cancer.
AB  - PURPOSE: Sipuleucel-T (APC8015) is an investigational immunotherapy product
      designed to stimulate T-cell immunity against prostatic acid phosphatase. A phase
      III study was undertaken to evaluate the safety and efficacy of sipuleucel-T in a
      placebo-controlled study. PATIENTS AND METHODS: A total of 127 patients with
      asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly
      assigned in a 2:1 ratio to receive three infusions of sipuleucel-T (n = 82) or
      placebo (n = 45) every 2 weeks. On disease progression, placebo patients could
      receive APC8015F, a product made with frozen leukapheresis cells. RESULTS: Of the
      127 patients, 115 patients had progressive disease at the time of data analysis,
      and all patients were followed for survival for 36 months. The median for time to
      disease progression (TTP) for sipuleucel-T was 11.7 weeks compared with 10.0
      weeks for placebo (P = .052, log-rank; hazard ratio [HR], 1.45; 95%CI, 0.99 to
      2.11). Median survival was 25.9 months for sipuleucel-T and 21.4 months for
      placebo (P = .01, log-rank; HR, 1.70; 95%CI, 1.13 to 2.56). Treatment remained a
      strong independent predictor of overall survival after adjusting for prognostic
      factors using a Cox multivariable regression model (P = .002, Wald test; HR,
      2.12; 95%CI, 1.31 to 3.44). The median ratio of T-cell stimulation at 8 weeks to
      pretreatment was eight-fold higher in sipuleucel-T-treated patients (16.9 v 1.99;
      P < .001). Sipuleucel-T therapy was well tolerated. CONCLUSION: While the
      improvement in the primary end point TTP did not achieve statistical
      significance, this study suggests that sipuleucel-T may provide a survival
      advantage to asymptomatic HRPC patients. Supportive studies are underway.

PMID- 16809735
TI  - Formulas calculating creatinine clearance are inadequate for determining
      eligibility for Cisplatin-based chemotherapy in bladder cancer.
AB  - PURPOSE: Efficacy of formulas calculating creatinine clearance (CrCl) to
      determine renal function eligibility (CrCl > 60 mL/min) for cisplatin-based
      chemotherapy has not been examined adequately in the bladder cancer population.
      We hypothesize these formulas may underestimate measured CrCl, and therefore the
      eligibility for cisplatin-based chemotherapy. PATIENTS AND METHODS: A database of
      208 patients with unresectable or metastatic bladder cancer treated on protocol
      at Memorial Sloan-Kettering Cancer Center (New York, NY) with cisplatin-based
      chemotherapy between 1983 and 1994 was examined retrospectively. The association
      between measured and calculated CrCl and the ability to complete three cycles
      (minimum therapeutic) of chemotherapy was examined. RESULTS: Baseline measured
      CrCl was less than 60 mL/min in 16% compared with 12% to 44% using various
      formulas. Concordance between calculated and measured CrCl less than 60 mL/min
      was poor (range of kappa, 0.14 to 0.38). In patients older than age 65, 22% had a
      measured CrCl less than 60 mL/min, compared with 10% to 63% calculated using
      various formulas. Overall, 80% completed at least three cycles of cisplatin-based
      chemotherapy. The ability to complete at least three cycles was statistically
      significantly related with a measured CrCl more than 60 mL/min (P = .02), but not
      with calculated CrCl more than 60 mL/min. CONCLUSION: Current formulas estimating
      CrCl tend to underestimate measured CrCl, especially in those older than 65
      years. Depending on the formula used, up to 44% who actually received cisplatin
      based chemotherapy based on measured CrCl would be deemed ineligible at present,
      potentially affecting survival outcomes. Methodology for determining CrCl and/or
      renal eligibility for cisplatin-based chemotherapy in patients with bladder
      cancer should be re-examined.

PMID- 16809736
TI  - Renal cell carcinoma recurrence after nephrectomy for localized disease:
      predicting survival from time of recurrence.
AB  - PURPOSE: Prognostic factors for patients with metastatic renal cell carcinoma
      (RCC) are well established. However, the risk profile is unknown for patients
      with recurrent RCC after a nephrectomy for localized disease. PATIENTS AND
      METHODS: From January 1989 to July 2005, we identified patients with localized
      RCC treated by nephrectomy who subsequently developed recurrent disease. We
      applied a validated prognostic scoring system previously developed for patients
      with metastatic RCC. Each patient was given a total risk score of 0 to 5, with
      one point for each of five prognostic variables (recurrence < 12 months after
      nephrectomy, serum calcium > 10 mg/dL, hemoglobin < lower limit of normal,
      lactate dehydrogenase > 1.5x upper limit of normal, and Karnofsky performance
      status < 80%). Patients were categorized into low- (score = 0), intermediate-
      (score = 1 to 2), and high-risk subgroups (score = 3 to 5). RESULTS: Our final
      cohort included 118 patients, with a median survival time of 21 months from the
      time of recurrence. Median follow-up time for survivors was 27 months. Overall
      survival was strongly associated with risk group category (P < .0001). Low-risk,
      intermediate-risk, and high-risk criteria were fulfilled in 34%, 50%, and 16% of
      patients, respectively. Median survival time for low-risk, intermediate-risk, and
      high-risk patients was 76, 25, and 6 months, respectively. Two-year overall
      survival rates for low-risk, intermediate-risk, and high-risk patients were 88%
      (95% CI, 77% to 99%), 51% (95% CI, 37% to 65%), and 11% (95% CI, 0% to 24%),
      respectively. CONCLUSION: At disease recurrence after nephrectomy for localized
      disease, a scoring system based on objective clinical and laboratory data
      provides meaningful risk stratification for both patient counseling and clinical
      trial entry.

PMID- 16809737
TI  - Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive
      systemic chemotherapy and delayed CNS radiation: a pediatric oncology group
      study.
AB  - PURPOSE: Prognosis and outcome of children with isolated CNS relapse of acute
      lymphoblastic leukemia (ALL) has depended on duration of first complete remission
      (CR1). This study intensified systemic therapy by delaying CNS radiation for 12
      months and tailored CNS radiation by CR1 duration. PATIENTS AND METHODS: Seventy
      six children with first isolated CNS relapse of ALL were treated with systemic
      chemotherapy that effectively penetrates into the CSF and intrathecal
      chemotherapy for 12 months. Patients with CR1 of less than 18 months received
      craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18
      months or more received cranial radiation only (18 Gy), followed by maintenance
      chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up
      front therapeutic window. RESULTS: Seventy-four (97.4%) of 76 eligible patients
      achieved a second remission. Overall 4-year event-free survival (EFS) for the 71
      precursor B-cell patients was 70.1% +/- 5.8%. CR1 duration and National Cancer
      Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at
      initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and
      18 months or more had a 4-year EFS of 51.6% +/- 11.3% and 77.7% +/- 6.4% (P =
      .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% +/-
      10.8% and 80.2% +/- 6.3% (P = .0018), respectively. A significant difference in
      EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of
      less than 18 months and high risk/CR1 of at least 18 months groups was detected
      (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most
      relapses involved the bone marrow, and three second malignancies were reported.
      CONCLUSION: Twelve months of intensive systemic chemotherapy with reduced dose
      cranial radiation (18 Gy) is highly effective for children with isolated CNS
      relapse and CR1 of 18 months or more. Novel strategies are needed for patients
      with CR1 of less than 18 months.

PMID- 16809738
TI  - Phase II multicenter study of neoadjuvant biochemotherapy for patients with stage
      III malignant melanoma.
AB  - PURPOSE: To determine the relapse-free survival, overall survival, and response
      rate of patients with stage III melanoma treated with neoadjuvant biochemotherapy
      in a multicenter setting. PATIENTS AND METHODS: Patients with pathologically
      proven stage III melanoma, either via clinical detection or sentinel lymph node
      positivity, were eligible for enrollment. Patients received two cycles of
      preoperative biochemotherapy followed by complete regional lymphadenectomy and
      two postoperative courses of biochemotherapy. The biochemotherapy regimen
      consisted of the following: cisplatin 20 mg/m2 on days 1 to 4, dacarbazine 800
      mg/m2 on day 1 only, vinblastine 1.6 mg/m2 on days 1 to 4, interleukin-2 total
      dose of 36 MU/m2 during 4 days, and interferon alfa 5 MU/m2 on days 1 to 5.
      Growth factor support was administered with each cycle. RESULTS: Ninety-two
      patients were eligible for the study. At a median follow-up of 40.4 months,
      relapse-free survival and overall survival are 64% and 78%, respectively. There
      was a lower relapse rate and improved survival for patients with a positive
      sentinel lymph node compared with patients with clinically detected lymph nodes,
      although this difference did not reach statistical significance. Of the 50
      patients with measurable disease, the overall response rate was 26%. Toxicity of
      the biochemotherapy was high but generally manageable. CONCLUSION: The current
      study has expanded the preliminary evidence on neoadjuvant biochemotherapy for
      stage III melanoma.

PMID- 16809739
TI  - Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon
      alfa-2b induces objective tumor regression in association with modulation of
      tumor infiltrating host cellular immune responses.
AB  - PURPOSE: Adjuvant high-dose interferon-alfa-2b (HDI) improves disease-free and
      overall survival in patients with high-risk melanoma. However, its mechanism of
      action is largely unknown. Therefore, HDI was investigated in the neoadjuvant
      setting to assess clinical and pathologic responses after 4 weeks of HDI and to
      perform immunohistochemical evaluation of immune cell subsets and melanoma
      associated antigens. PATIENTS AND METHODS: Patients with palpable regional lymph
      node metastases from melanoma (American Joint Committee on Cancer stage IIIB-C)
      underwent surgical biopsy at study entry and then received standard intravenous
      HDI (20 million units/m2, 5 days per week) for 4 weeks followed by complete
      lymphadenectomy and standard maintenance subcutaneous HDI (10 million units/m2 3
      times per week) for 48 weeks. Biopsy samples were obtained before and after
      intravenous HDI and subjected to immunohistochemical analysis as well as routine
      pathologic study. RESULTS: Twenty patients were enrolled, and biopsy samples were
      informative for 17. Eleven patients (55%) demonstrated objective clinical
      response, and 3 patients (15%) had complete pathologic response. At a median
      follow-up of 18.5 months (range, 7 months to 50 months) 10 patients had no
      evidence of recurrent disease. Clinical responders had significantly greater
      increases in endotumoral CD11c+ and CD3+ cells and significantly greater
      decreases in endotumoral CD83+ cells compared with nonresponders. No changes in
      the expression of melanoma-associated lineage antigens, tumor cell proliferation,
      angiogenesis, or apoptosis were evident. CONCLUSION: Neoadjuvant HDI is highly
      effective for the treatment of palpable stage IIIB-C melanoma, and the findings
      of this study implicate an indirect immunomodulatory mechanism rather than a
      direct antitumor mechanism.

PMID- 16809740
TI  - Anatomic site, sun exposure, and risk of cutaneous melanoma.
AB  - PURPOSE: Sunlight is the principal environmental risk factor for cutaneous
      melanoma. A current hypothesis postulates that the role of sunlight in causing
      melanoma differs according to anatomic site. We tested this hypothesis in a
      population-based case-case comparative study of melanoma patients. METHODS:
      Patients were sampled from the Queensland cancer registry in three groups:
      superficial spreading or nodular melanomas of the trunk (n = 154), of the head
      and neck (HN; n = 76), and lentigo maligna (LM) and lentigo maligna melanoma
      (LMM; for both LM and LMM, n = 76). Data were collected on school-age sun
      exposure and occupational and recreational sun exposure in adulthood. Odds ratios
      (OR) and 95% CIs were calculated using polytomous logistic regression. RESULTS:
      HN melanoma patients were substantially more likely than trunk patients to have
      higher levels of sun exposure in adulthood (OR, 2.43; 95% CI, 0.98 to 5.99) and
      specifically, higher levels of occupational exposure (OR, 3.25; 95% CI, 1.32 to
      8.00), but lower levels of recreational sun exposure (OR, 0.50; 95% CI, 0.21 to
      1.19). LM and LMM patients reported higher occupational exposure and lower
      recreational sun exposure than trunk melanoma patients, although this was not
      significant. We found no significant differences between the groups for school
      age sun exposures. CONCLUSION: Melanomas developing at different body sites are
      associated with distinct patterns of sun exposure. Melanomas of the head and neck
      are associated with chronic patterns of sun exposure whereas trunk melanomas are
      associated with intermittent patterns of sun exposure, supporting the hypothesis
      that melanomas may arise through divergent causal pathways.

PMID- 16809741
TI  - Health-related quality of life measurement in randomized clinical trials in
      surgical oncology.
AB  - PURPOSE: There is debate about the value of measuring health-related quality of
      life (HRQL) in clinical trials in oncology because of evidence suggesting that
      HRQL does not influence clinical decisions. Analysis of HRQL in surgical trials,
      however, may inform decision making because it provides detailed assessment of
      the immediate detrimental short-term impact of surgery on HRQL that needs to be
      considered against the long-term survival benefits and functional outcomes of
      surgery. This study evaluated whether HRQL in randomized trials in surgical
      oncology contributes to clinical decision making. METHODS: A systematic review
      identified randomized trials in surgical oncology with HRQL. Trials were
      evaluated independently by two reviewers and the value of HRQL in clinical
      decision making was categorized in three ways: whether trial investigators
      reported that HRQL influenced final treatment recommendations, whether trial
      investigators reported that HRQL would be useful for informed consent, and
      whether HRQL was assessed robustly according to predefined criteria. RESULTS:
      Thirty-three randomized trials with valid HRQL questionnaires were identified; 22
      (67%) concluded that HRQL outcomes influenced treatment decisions or provided
      valuable data for informed consent, and seven of these trials had robust HRQL
      design. Another five trials had robust HRQL design but investigators reported
      that HRQL outcomes were not clinically important enough to influence treatment
      recommendations. CONCLUSION: In surgical trials in oncology, HRQL informed
      clinical decision making. It is recommended that HRQL be included in relevant
      surgical trials, and that information be used to inform clinicians and patients
      about the impact of surgery on short- and long-term HRQL.

PMID- 16809742
TI  - Learning to listen: a fellow's experience.

PMID- 16809743
TI  - What about the family when a terminally ill cancer patient makes a request for
      euthanasia?

PMID- 16809744
TI  - Promising new treatment schedule for gefitinib responders after severe
      hepatotoxicity with daily administration.

PMID- 16809745
TI  - Important bias in the Astragalus meta-analysis.

PMID- 16809746
TI  - Breaking bad news: more than just guidelines.

PMID- 16809748
TI  - FDA: regulations will clarify pedigree requirements: loopholes remain in PDMA
      law.

PMID- 16809747
TI  - Cytogenetic abnormalities can change during the course of the disease process in
      chronic lymphocytic leukemia.

PMID- 16809749
TI  - Drug risks and benefits poorly communicated, experts contend.

PMID- 16809750
TI  - Citizens' group calls for universal health benefits by 2012.

PMID- 16809751
TI  - Managing the effect of the average sales price. Interviewed by Donna Young.

PMID- 16809752
TI  - Development and clinical outcomes of pharmacist-managed diabetes care clinics.
AB  - PURPOSE: The development and outcomes of two pharmacist-managed diabetes care
      clinics (DCCs) are described. METHODS: Retrospective data analysis was performed
      to determine the outcomes for patients with type 2 diabetes mellitus who were
      treated in two pharmacist-managed DCCs. Primary outcome measures included changes
      in glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, body mass index,
      low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein cholesterol,
      triglycerides, and blood pressure and documented annual retinal and micro-albumin
      screening. Secondary outcome measures included the use of aspirin and kidney
      sparing agents and annual screening for thyroid-stimulating hormone. RESULTS:
      Data from 113 patients in the DCCs were analyzed. After one year, the mean
      reduction in HbA(1c) levels was 1.3%, with a mean HbA(1c) of 7.8%. HbA(1c) goals
      were based on the institution's HbA(1c) normal range of 4.1-6.5%. Compared with
      baseline, over one third of patients met the HbA(1c) and blood pressure goals of
      <7.5% and <130/80 mm Hg, respectively. Mean LDL cholesterol concentration
      decreased from 110 to 94 mg/dL. The mean concentration of triglycerides decreased
      from 243 to 178 mg/dL. Mean systolic blood pressure decreased from 136 to 132 mm
      Hg. Whereas the national average for uncontrolled diabetes (HbA(1c) > 9.5%) was
      36.9%, only 3.5% of patients at the pharmacist-managed DCCs had uncontrolled
      diabetes. Attainment rates of LDL cholesterol goals and annual retinal and
      microalbumin screenings were significantly higher in clinic patients compared
      with national averages. Three-year postclinic inception data revealed similar
      favorable outcomes, most notably an average HbA(1c) of 7.6% and 55% of patients
      meeting their target HbA(1c) goal of <7.5%. CONCLUSION: Compared with national
      averages, DCCs managed by clinical pharmacists achieved higher screening rates
      and attained treatment goals more often.

PMID- 16809753
TI  - A PHS pharmacist team's response to Hurricane Katrina.
AB  - PURPOSE: The challenges and victories that a team of Public Health Service (PHS)
      pharmacists experienced in establishing pharmacy operations at a federal medical
      station and conducting outreach missions are described. SUMMARY: The Gulf coast
      of Mississippi and southeast Louisiana were struck on August 29, 2005, by
      Hurricane Katrina, which caused widespread infrastructure damage, flooding, and
      loss of life. A team of 70 officers, which included 8 pharmacists, arrived on
      September 3 and 4 to establish a 480-bed federal medical station in an aircraft
      hangar at the naval air station (NAS) in Meridian, Mississippi. Numerous
      challenges were encountered, including identifying a secure space for a pharmacy,
      determining how to manage the immediate shortage of medications, devising a
      dispensing system specific to controlled medications, handling personal
      medications brought in by patients, and maintaining adequate pharmacy staffing to
      provide for hospital needs. Two outreach efforts were also undertaken. The first
      was to assist the NAS pharmacy department, which was overwhelmed with nearly 800
      Navy and Coast Guard personnel who were displaced to the Meridian NAS. The second
      outreach effort was to augment the staff at a local free clinic in Meridian,
      which needed help to set up their clinic so they could handle the influx of
      hurricane victims who were arriving daily. CONCLUSION: A team of PHS pharmacists
      established a pharmacy, provided pharmaceutical care, and conducted outreach
      programs to aid victims of Hurricane Katrina.

PMID- 16809754
TI  - Impact of United States Pharmacopeia chapter 797: results of a national survey.
AB  - PURPOSE: The initial response of the pharmacy profession to United States
      Pharmacopeia (USP) chapter 797 and the current state of hospital pharmacy
      practice as it relates to implementing this chapter were studied. METHODS: A
      stratified random sample of 600 hospital pharmacy directors across the nation
      were surveyed by mail. RESULTS: A total of 251 surveys (41.8%) were returned.
      Larger hospitals (> or =200 staffed beds) were more likely than smaller hospitals
      (<200 staffed beds) to have read USP chapter 797 (80.0% versus 45.8%,
      respectively) and have a copy of the chapter (94.6% versus 78.0%, respectively).
      Overall, respondents felt that chapter 797 would negatively affect workload and
      pharmacy's ability to provide sterile preparations in a timely manner.
      Conversely, respondents replied that the new standard would have a positive
      effect on the quality of care provided by the hospital. Overall, 45.3% of
      respondents reported plans to build a clean-room, and 21.7% reported plans to
      obtain new equipment to comply with chapter 797. Furthermore, 42.3% of
      respondents had decreased the quantity of high-risk compounding. Respondents also
      reported that their pharmacy's budget had increased in order to comply with
      chapter 797. The most common requirements with which respondents were not willing
      to comply were validating the accuracy of automated compounding devices,
      sterilizing products and equipment before entering the cleanroom, rotating the
      type of disinfectants, and prohibiting use of cosmetics by staff. CONCLUSION: USP
      chapter 797 standards have influenced the compounding practices of hospital
      pharmacies nationwide, including a decrease in the compounding of high-risk
      preparations, an increase in budgetary allocations, and implementation of better
      quality assurance practices. Larger hospitals tended to implement more changes
      than did smaller hospitals, and there remains room for improvement overall.

PMID- 16809755
TI  - Incorporation of a gentamicin dosage calculator into a computerized prescriber
      order-entry system.

PMID- 16809756
TI  - Applying antimicrobial pharmacodynamics to resistant gram-negative pathogens.
AB  - PURPOSE: Guided antibiotic adjustment for the treatment of multidrug-resistant,
      gram-negative pathogens is explored. SUMMARY: Multidrug-resistant pathogens are
      being isolated with increasing frequency, while the production of novel agents to
      circumvent resistance has slowed to a near halt. Hence, antimicrobial adjustment
      based on drug pharmacokinetic and pharmacodynamic properties has moved to the
      forefront of treatment. Pharmacodynamic principles for major classes of
      antimicrobials are reviewed, and the use of susceptibility reports to optimize
      pharmacodynamics to treat gram-negative infections is described. The need for the
      application of antimicrobial pharmacodynamics continues to grow as resistance to
      the agents becomes more common. Susceptibility reports, including antibiograms,
      and their limitations are briefly discussed. The resistance profiles of the beta
      lactams (including carbapenems), aminoglycosides, fluoroquinolones, tetracyclines
      and glycylcyclines, and the polymyxins are reviewed, and the pharmacodynamic
      optimization of these profiles is explored. CONCLUSION: Various mechanisms
      account for resistance of bacteria to antibiotics. The appropriate use of
      pharmacokinetics and pharmacodynamics can guide antibiotic therapy and enhance
      the likelihood of success.

PMID- 16809758
TI  - Actions of the ASHP Board of Directors--meeting of April 19-21, 2006.

PMID- 16809757
TI  - Drug pricing model in a pediatric hospital.

PMID- 16809759
TI  - The cochaperone p23 differentially regulates estrogen receptor target genes and
      promotes tumor cell adhesion and invasion.
AB  - The cochaperone p23 plays an important role in estrogen receptor alpha (ER)
      signal transduction. In this study, we investigated how p23 regulates ER target
      gene activation and affects tumor growth and progression. Remarkably, we found
      that changes in the expression of p23 differentially affected the activation of
      ER target genes in a manner dependent upon the type of DNA regulatory element.
      p23 overexpression enhanced the expression of the ER target genes cathepsin D and
      pS2, which are regulated by direct DNA binding of ER to estrogen response
      elements (ERE). In contrast, the expression of other target genes, including c
      Myc, cyclin D1, and E2F1, to which ER is recruited indirectly through its
      interaction with other transcription factors remains unaffected by changes in p23
      levels. The p23-induced expression of pS2 is associated with enhanced recruitment
      of ER to the ERE in the promoter, whereas ER recruitment to the ERE-less c-Myc
      promoter does not respond to p23. Intriguingly, p23-overexpressing MCF-7 cells
      exhibit increased adhesion and invasion in the presence of fibronectin. Our
      findings demonstrate that p23 differentially regulates ER target genes and is
      involved in the control of distinct cellular processes in breast tumor
      development, thus revealing novel functions of this cochaperone.

PMID- 16809760
TI  - 3BP2 deficiency impairs the response of B cells, but not T cells, to antigen
      receptor ligation.
AB  - The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav,
      and phospholipase C-gamma (PLC-gamma); and is thought to be important for
      interleukin-2 gene transcription in T cells. To define the role of 3BP2 in
      lymphocyte development and function, we generated 3BP2-deficient mice. T-cell
      development, proliferation, cytokine secretion, and signaling in response to T
      cell receptor (TCR) ligation were all normal in 3BP2(-/-) mice. 3BP2(-/-) mice
      had increased accumulation of pre-B cells in the bone marrow and a block in the
      progression of transitional B cells in the spleen from the T1 to the T2 stage,
      but normal numbers of mature B cells. B-cell proliferation, cell cycle
      progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp
      dephosphorylation, and Erk and Jnk activation in response to B-cell receptor
      (BCR) ligation were all impaired. These results suggest that 3BP2 is important
      for BCR, but not for TCR signaling.

PMID- 16809761
TI  - A feed-forward repression mechanism anchors the Sin3/histone deacetylase and N
      CoR/SMRT corepressors on chromatin.
AB  - Transcription in eukaryotes is governed in part by histone acetyltransferase
      (HAT)- and histone deacetylase (HDAC)-containing complexes that are recruited via
      activators and repressors, respectively. Here, we show that the Sin3/HDAC and N
      CoR/SMRT corepressor complexes repress transcription from histone H3- and/or H4
      acetylated nucleosomal templates in vitro. Repression of histone H3-acetylated
      templates was completely dependent on the histone deacetylase activity of the
      corepressor complexes, whereas this activity was not required to repress H4
      acetylated templates. Following deacetylation, both complexes become stably
      anchored in a repressor-independent manner to nucleosomal templates containing
      hypoacetylated histone H3, but not H4, resulting in dominance of repression over
      activation. The observed stable anchoring of corepressor complexes casts doubt on
      the view of a dynamic balance between readily exchangeable HAT and HDAC
      activities regulating transcription and implies that pathways need to be in place
      to actively remove HDAC complexes from hypoacetylated promoters to switch on
      silent genes.

PMID- 16809763
TI  - The scaffold protein Cybr is required for cytokine-modulated trafficking of
      leukocytes in vivo.
AB  - Trafficking and cell adhesion are key properties of cells of the immune system.
      However, the molecular pathways that control these cellular behaviors are still
      poorly understood. Cybr is a scaffold protein highly expressed in the
      hematopoietic/immune system whose physiological role is still unknown. In vitro
      studies have shown it regulates LFA-1, a crucial molecule in lymphocyte
      attachment and migration. Cybr also binds cytohesin-1, a guanine nucleotide
      exchange factor for the ARF GTPases, which affects actin cytoskeleton remodeling
      during cell migration. Here we show that expression of Cybr in vivo is
      differentially modulated by type 1 cytokines during lymphocyte maturation. In
      mice, Cybr deficiency negatively affects leukocytes circulating in blood and
      lymphocytes present in the lymph nodes. Moreover, in a Th1-polarized mouse model,
      lymphocyte trafficking is impaired by loss of Cybr, and Cybr-deficient mice with
      aseptic peritonitis have fewer cells than controls present in the peritoneal
      cavity, as well as fewer leukocytes leaving the bloodstream. Mutant mice injected
      with Moloney murine sarcoma/leukemia virus develop significantly larger tumors
      than wild-type mice and have reduced lymph node enlargement, suggesting reduced
      cytotoxic T-lymphocyte migration. Taken together, these data support a role for
      Cybr in leukocyte trafficking, especially in response to proinflammatory
      cytokines in stress conditions.

PMID- 16809762
TI  - Tpa1p is part of an mRNP complex that influences translation termination, mRNA
      deadenylation, and mRNA turnover in Saccharomyces cerevisiae.
AB  - In this report, we show that the Saccharomyces cerevisiae protein Tpa1p (for
      termination and polyadenylation) influences translation termination efficiency,
      mRNA poly(A) tail length, and mRNA stability. Tpa1p is encoded by the previously
      uncharacterized open reading frame YER049W. Yeast strains carrying a deletion of
      the TPA1 gene (tpa1Delta) exhibited increased readthrough of stop codons, and
      coimmunoprecipitation assays revealed that Tpa1p interacts with the translation
      termination factors eRF1 and eRF3. In addition, the tpa1Delta mutation led to a
      1.5- to 2-fold increase in the half-lives of mRNAs degraded by the general 5'-
      >3' pathway or the 3'-->5' nonstop decay pathway. In contrast, this mutation did
      not have any affect on the nonsense-mediated mRNA decay pathway. Examination of
      mRNA poly(A) tail length revealed that poly(A) tails are longer than normal in a
      tpa1Delta strain. Consistent with a potential role in regulating poly(A) tail
      length, Tpa1p was also found to coimmunoprecipitate with the yeast poly(A)
      binding protein Pab1p. These results suggest that Tpa1p is a component of a
      messenger ribonucleoprotein complex bound to the 3' untranslated region of mRNAs
      that affects translation termination, deadenylation, and mRNA decay.

PMID- 16809764
TI  - Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B)
      protein from ubiquitin-mediated degradation.
AB  - Histone deacetylases (HDACs) are enzymes that regulate the functions of histones
      as well as nonhistones by catalyzing the removal of acetyl groups from lysine
      residues. HDACs regulate many biological processes, including the cell division
      cycle and tumorigenesis. Although recent studies have implicated HDAC8 in tumor
      cell proliferation, the molecular mechanisms linking HDAC8 to cell growth remain
      unknown. Here, we report that the human ortholog of the yeast ever-shorter
      telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase
      A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin
      mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a
      complex that inhibits the CHIP (C-terminal heat shock protein interacting
      protein) E3 ligase-mediated degradation of hEST1B. Importantly, HDAC8 regulation
      of hEST1B protein stability modulates total telomerase enzymatic activity. Our
      findings reveal a novel mechanism by which HDAC8 contributes to tumorigenesis by
      regulating telomerase activity.

PMID- 16809766
TI  - Wnt activation and alternative promoter repression of LEF1 in colon cancer.
AB  - Alternative promoters within the LEF1 locus produce polypeptides of opposing
      biological activities. Promoter 1 produces full-length LEF-1 protein, which
      recruits beta-catenin to Wnt target genes. Promoter 2 produces a truncated form
      that cannot interact with beta-catenin and instead suppresses Wnt regulation of
      target genes. Here we show that promoter 1 is aberrantly activated in colon
      cancers because it is a direct target of the Wnt pathway. T-cell factor (TCF)
      beta-catenin complexes bind to Wnt response elements in exon 1 and dynamically
      regulate chromatin acetylation and promoter 1 activity. Promoter 2 is delimited
      to the intron 2/exon 3 boundary and, like promoter 1, is also directly regulated
      by TCF-beta-catenin complexes. Promoter 2 is nevertheless silent in colon cancer
      because an upstream repressor selectively targets the basal promoter leading to
      destabilized TCF-beta-catenin binding. We conclude that the biological outcome of
      aberrant LEF1 activation in colon cancer is directed by differential promoter
      activation and repression.

PMID- 16809765
TI  - Differential binding of replication proteins across the human c-myc replicator.
AB  - The binding of the prereplication complex proteins Orc1, Orc2, Mcm3, Mcm7, and
      Cdc6 and the novel DNA unwinding element (DUE) binding protein DUE-B to the
      endogenous human c-myc replicator was studied by chromatin immunoprecipitation.
      In G(1)-arrested HeLa cells, Mcm3, Mcm7, and DUE-B were prominent near the DUE,
      while Orc1 and Orc2 were least abundant near the DUE and more abundant at
      flanking sites. Cdc6 binding mirrored that of Orc2 in G(1)-arrested cells but
      decreased in asynchronous or M-phase cells. Similarly, the signals from Orc1,
      Mcm3, and Mcm7 were at background levels in cells arrested in M phase, whereas
      Orc2 retained the distribution seen in G(1)-phase cells. Previously shown to
      cause histone hyperacetylation and delocalization of replication initiation,
      trichostatin A treatment of cells led to a parallel qualitative change in the
      distribution of Mcm3, but not Orc2, across the c-myc replicator. Orc2, Mcm3, and
      DUE-B were also bound at an ectopic c-myc replicator, where deletion of sequences
      essential for origin activity was associated with the loss of DUE-B binding or
      the alteration of chromatin structure and loss of Mcm3 binding. These results
      show that proteins implicated in replication initiation are selectively and
      differentially bound across the c-myc replicator, dependent on discrete
      structural elements in DNA or chromatin.

PMID- 16809767
TI  - Mechanistic studies of the mitotic activation of Mos.
AB  - The protein kinase Mos is responsible for the activation of MEK1 and p42 mitogen
      activated protein kinase during Xenopus oocyte maturation and during mitosis in
      Xenopus egg extracts. Here we show that the activation of Mos depends upon the
      phosphorylation of Ser 3, a residue previously implicated in the regulation of
      Mos stability; the dephosphorylation of Ser 105, a previously unidentified
      phosphorylation site conserved in Mos proteins; and the regulated dissociation of
      Mos from CK2beta. Mutation of Ser 3 to alanine and/or mutation of Ser 105 to
      glutamate produces a Mos protein that is defective for M-phase activation, as
      assessed by in vitro kinase assays, and defective for induction of oocyte
      maturation and maintenance of the spindle assembly checkpoint in extracts.
      Interestingly, Ser 105 is situated at the beginning of helix alphaC in the N
      terminal lobe of the Mos kinase domain. Changes in the orientation of this helix
      have been previously implicated in the activation of Cdk2 and Src family tyrosine
      kinases. Our work suggests that Ser 105 dephosphorylation represents a novel
      mechanism for reorienting helix alphaC.

PMID- 16809768
TI  - Prostate-specific membrane antigen regulates angiogenesis by modulating integrin
      signal transduction.
AB  - The transmembrane peptidase prostate-specific membrane antigen (PSMA) is
      universally upregulated in the vasculature of solid tumors, but its functional
      role in tumor angiogenesis has not been investigated. Here we show that
      angiogenesis is severely impaired in PSMA-null animals and that this angiogenic
      defect occurs at the level of endothelial cell invasion through the extracellular
      matrix barrier. Because proteolytic degradation of the extracellular matrix is a
      critical component of endothelial invasion in angiogenesis, it is logical to
      assume that PSMA participates in matrix degradation. However, we demonstrate a
      novel and more complex role for PSMA in angiogenesis, where it is a principal
      component of a regulatory loop that is tightly modulating laminin-specific
      integrin signaling and GTPase-dependent, p21-activated kinase 1 (PAK-1) activity.
      We show that PSMA inhibition, knockdown, or deficiency decreases endothelial cell
      invasion in vitro via integrin and PAK, thus abrogating angiogenesis.
      Interestingly, the neutralization of beta(1) or the inactivation of PAK increases
      PSMA activity, suggesting that they negatively regulate PSMA. This negative
      regulation is mediated by the cytoskeleton as the disruption of interactions
      between the PSMA cytoplasmic tail and the anchor protein filamin A decreases PSMA
      activity, integrin function, and PAK activation. Finally, the inhibition of PAK
      activation enhances the PSMA/filamin A interaction and, thus, boosts PSMA
      activity. These data imply that PSMA participates in an autoregulatory loop,
      wherein active PSMA facilitates integrin signaling and PAK activation, leading to
      both productive invasion and downregulation of integrin beta(1) signaling via
      reduced PSMA activity. Therefore, we have identified a novel role for PSMA as a
      true molecular interface, integrating both extracellular and intracellular
      signals during angiogenesis.

PMID- 16809769
TI  - Analysis of human histone H2AZ deposition in vivo argues against its direct role
      in epigenetic templating mechanisms.
AB  - Chromatin is considered to be a principal carrier of epigenetic information due
      to the ability of alternative chromatin states to persist through generations of
      cell divisions and to spread on DNA. Replacement histone variants are novel
      candidates for epigenetic marking of chromatin. We developed a novel approach to
      analyze the chromatin environment of nucleosomes containing a particular
      replacement histone. We applied it to human H2AZ, one of the most studied
      alternative histones. We find that neither H2AZ itself nor other features of the
      H2AZ-containing nucleosome spread to the neighboring nucleosomes in vivo, arguing
      against a role for H2AZ as a self-perpetuating epigenetic mark.

PMID- 16809770
TI  - 5'-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose
      deprivation conditions found in solid-tumor microenvironments.
AB  - Low oxygen gradients (hypoxia and anoxia) are important determinants of
      pathological conditions under which the tissue blood supply is deficient or
      defective, such as in solid tumors. We have been investigating the relationship
      between the activation of hypoxia-inducible factor 1 (HIF-1), the primary
      transcriptional regulator of the mammalian response to hypoxia, and 5'-AMP
      activated protein kinase (AMPK), another regulatory system important for
      controlling cellular energy metabolism. In the present study, we used mouse
      embryo fibroblasts nullizygous for HIF-1alpha or AMPK expression to show that
      AMPK is rapidly activated in vitro by both physiological and pathophysiological
      low-oxygen conditions, independently of HIF-1 activity. These findings imply that
      HIF-1 and AMPK are components of a concerted cellular response to maintain energy
      homeostasis in low-oxygen or ischemic-tissue microenvironments. Finally, we used
      transformed derivatives of wild-type and HIF-1alpha- or AMPKalpha-null mouse
      embryo fibroblasts to determine whether AMPK is activated in vivo. We obtained
      evidence that AMPK is activated in authentic hypoxic tumor microenvironments and
      that this activity overlaps with regions of hypoxia detected by a chemical probe.
      We also showed that AMPK is important for the growth of this tumor model.

PMID- 16809771
TI  - BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional
      promoter and are overexpressed in diffuse large B-cell lymphomas with a prominent
      inflammatory infiltrate.
AB  - BAL1 is a transcription modulator that is overexpressed in chemoresistant,
      diffuse large B-cell lymphomas (DLBCLs). BAL1 complexes with a recently described
      DELTEX family member termed BBAP. Herein, we characterized BAL1 and BBAP
      expression in primary DLBCL subtypes defined by their comprehensive
      transcriptional profiles. BAL1 and BBAP were most abundant in lymphomas with a
      brisk host inflammatory response, designated host response (HR) tumors. Although
      these DLBCLs include significant numbers of tumor-infiltrating lymphocytes and
      interdigitating dendritic cells, BAL1 and BBAP were expressed primarily by
      malignant B cells, prompting speculation that the genes might be induced by host
      derived inflammatory mediators such as gamma interferon (IFN-gamma). In fact, IFN
      gamma induced BAL1 and BBAP expression in DLBCL cell lines; doxycycline-induced
      BAL1 also increased the expression of multiple IFN-stimulated genes, directly
      implicating BAL1 in an IFN signaling pathway. We show that BAL1 and BBAP are
      located on chromosome 3q21 in a head-to-head orientation and are regulated by a
      IFN-gamma-responsive bidirectional promoter. BBAP regulates the subcellular
      localization of BAL1 by a dynamic shuttling mechanism, highlighting the
      functional requirement for coordinated BBAP and BAL1 expression. IFN-gamma
      induced BAL1/BBAP expression contributes to the molecular signature of HR DLBCLs
      and highlights the interplay between the inflammatory infiltrate and malignant B
      cells in these tumors.

PMID- 16809772
TI  - Stabilization of the retinoblastoma protein by A-type nuclear lamins is required
      for INK4A-mediated cell cycle arrest.
AB  - Mutations in the LMNA gene, which encodes all A-type lamins, including lamin A
      and lamin C, cause a variety of tissue-specific degenerative diseases termed
      laminopathies. Little is known about the pathogenesis of these disorders.
      Previous studies have indicated that A-type lamins interact with the
      retinoblastoma protein (pRB). Here we probe the functional consequences of this
      association and further examine links between nuclear structure and cell cycle
      control. Since pRB is required for cell cycle arrest by p16(ink4a), we tested the
      responsiveness of multiple lamin A/C-depleted cell lines to overexpression of
      this CDK inhibitor and tumor suppressor. We find that the loss of A-type lamin
      expression results in marked destabilization of pRB. This reduction in pRB
      renders cells resistant to p16(ink4a)-mediated G(1) arrest. Reintroduction of
      lamin A, lamin C, or pRB restores p16(ink4a)-responsiveness to Lmna(-/-) cells.
      An array of lamin A mutants, representing a variety of pathologies as well as
      lamin A processing mutants, was introduced into Lmna(-/-) cells. Of these, a
      mutant associated with mandibuloacral dysplasia (MAD R527H), as well as two lamin
      A processing mutants, but not other disease-associated mutants, failed to restore
      p16(ink4a) responsiveness. Although our findings do not rule out links between
      altered pRB function and laminopathies, they fail to support such an assertion.
      These findings do link lamin A/C to the functional activation of a critical tumor
      suppressor pathway and further the possibility that somatic mutations in LMNA
      contribute to tumor progression.

PMID- 16809773
TI  - Mouse emi1 has an essential function in mitotic progression during early
      embryogenesis.
AB  - For successful mitotic entry and spindle assembly, mitosis-promoting factors are
      activated at the G(2)/M transition stage, followed by stimulation of the anaphase
      promoting complex (APC), an E3 ubiquitin ligase, to direct the ordered
      destruction of several critical mitotic regulators. Given that inhibition of APC
      activity is important for preventing premature or improper ubiquitination and
      destruction of substrates, several modulators and their regulation mechanisms
      have been studied. Emi1, an early mitotic inhibitor, is one of these regulatory
      factors. Here we show, by analyzing Emi1-deficient embryos, that Emi1 is
      essential for precise mitotic progression during early embryogenesis. Emi1(-/-)
      embryos were found to be lethal due to a defect in preimplantation development.
      Cell proliferation appeared to be normal, but mitotic progression was severely
      defective during embryonic cleavage. Moreover, multipolar spindles and misaligned
      chromosomes were frequently observed in Emi1 mutant cells, possibly due to
      premature APC activation. Our results collectively suggest that the late prophase
      checkpoint function of Emi1 is essential for accurate mitotic progression and
      embryonic viability.

PMID- 16809774
TI  - Role of p38 in replication of Trypanosoma brucei kinetoplast DNA.
AB  - Trypanosomes have an unusual mitochondrial genome, called kinetoplast DNA, that
      is a giant network containing thousands of interlocked minicircles. During
      kinetoplast DNA synthesis, minicircles are released from the network for
      replication as theta-structures, and then the free minicircle progeny reattach to
      the network. We report that a mitochondrial protein, which we term p38, functions
      in kinetoplast DNA replication. RNA interference (RNAi) of p38 resulted in loss
      of kinetoplast DNA and accumulation of a novel free minicircle species named
      fraction S. Fraction S minicircles are so underwound that on isolation they
      become highly negatively supertwisted and develop a region of Z-DNA. p38 binds to
      minicircle sequences within the replication origin. We conclude that cells with
      RNAi-induced loss of p38 cannot initiate minicircle replication, although they
      can extensively unwind free minicircles.

PMID- 16809775
TI  - The X and Y chromosomes assemble into H2A.Z-containing [corrected] facultative
      heterochromatin [corrected] following meiosis.
AB  - Spermatogenesis is a complex sequential process that converts mitotically
      dividing spermatogonia stem cells into differentiated haploid spermatozoa. Not
      surprisingly, this process involves dramatic nuclear and chromatin restructuring
      events, but the nature of these changes are poorly understood. Here, we linked
      the appearance and nuclear localization of the essential histone variant H2A.Z
      with key steps during mouse spermatogenesis. H2A.Z cannot be detected during the
      early stages of spermatogenesis, when the bulk of X-linked genes are transcribed,
      but its expression begins to increase at pachytene, when meiotic sex chromosome
      inactivation (MSCI) occurs, peaking at the round spermatid stage. Strikingly,
      when H2A.Z is present, there is a dynamic nuclear relocalization of
      heterochromatic marks (HP1beta and H3 di- and tri-methyl K9), which become
      concentrated at chromocenters and the inactive XY body, implying that H2A.Z may
      substitute for the function of these marks in euchromatin. We also show that the
      X and the Y chromosome are assembled into facultative heterochromatic structures
      postmeiotically that are enriched with H2A.Z, thereby replacing macroH2A. This
      indicates that XY silencing continues following MSCI. These results provide new
      insights into the large-scale changes in the composition and organization of
      chromatin associated with spermatogenesis and argue that H2A.Z has a unique role
      in maintaining sex chromosomes in a repressed state.

PMID- 16809776
TI  - Control of translocations between highly diverged genes by Sgs1, the
      Saccharomyces cerevisiae homolog of the Bloom's syndrome protein.
AB  - Sgs1 is a RecQ family DNA helicase required for genome stability in Saccharomyces
      cerevisiae whose human homologs BLM, WRN, and RECQL4 are mutated in Bloom's,
      Werner, and Rothmund Thomson syndromes, respectively. Sgs1 and mismatch repair
      (MMR) are inhibitors of recombination between similar but divergent (homeologous)
      DNA sequences. Here we show that SGS1, but not MMR, is critical for suppressing
      spontaneous, recurring translocations between diverged genes in cells with
      mutations in the genes encoding the checkpoint proteins Mec3, Rad24, Rad9, or
      Rfc5, the chromatin assembly factors Cac1 or Asf1, and the DNA helicase Rrm3. The
      S-phase checkpoint kinase and telomere maintenance factor Tel1, a homolog of the
      human ataxia telangiectasia (ATM) protein, prevents these translocations, whereas
      the checkpoint kinase Mec1, a homolog of the human ATM-related protein, and the
      Rad53 checkpoint kinase are not required. The translocation structures observed
      suggest involvement of a dicentric intermediate and break-induced replication
      with multiple cycles of DNA template switching.

PMID- 16809777
TI  - Ectodomain shedding of preadipocyte factor 1 (Pref-1) by tumor necrosis factor
      alpha converting enzyme (TACE) and inhibition of adipocyte differentiation.
AB  - Preadipocyte factor 1 (Pref-1), an epidermal growth factor repeat containing
      transmembrane protein found in the preadipocytes, inhibits adipocyte
      differentiation in vitro and in vivo. Here, we examined the processing of
      membrane form of Pref-1A to release the 50-kDa soluble form that inhibits
      adipocyte differentiation. The ectodomain cleavage of Pref-1 is markedly enhanced
      by phorbol 12-myristate 13-acetate in a dose- and time-dependent manner. The
      basal and stimulated cleavage is inhibited by the broad metalloproteinase
      inhibitor GM6001, a fact that suggests that cleavage of membrane Pref-1A is
      dependent on a metalloproteinase. Next, we showed that release of soluble Pref-1A
      is inhibited by TAPI-0 and by a tissue inhibitor of metalloproteinase-3, TIMP-3,
      that can inhibit tumor necrosis factor alpha converting enzyme (TACE), but not by
      TIMP-1 or TIMP-2. On the other hand, overexpression of TACE increases Pref-1
      cleavage to produce the 50-kDa soluble form. Furthermore, this cleavage was not
      detected in cells with TACE mutation or with TACE small interfering RNA. TACE
      mediated shedding of Pref-1 ectodomain inhibits adipocyte differentiation of 3T3
      L1 cells and in Pref-1-null mouse embryo fibroblasts transduced with Pref-1A.
      Identification of TACE as the major protease responsible for conversion of
      membrane-bound Pref-1 to the biologically active diffusible form provides a new
      insight into Pref-1 function in adipocyte differentiation.

PMID- 16809778
TI  - RNA polymerase I-specific subunit CAST/hPAF49 has a role in the activation of
      transcription by upstream binding factor.
AB  - Eukaryotic RNA polymerases are large complexes, 12 subunits of which are
      structurally or functionally homologous across the three polymerase classes. Each
      class has a set of specific subunits, likely targets of their cognate
      transcription factors. We have identified and characterized a human RNA
      polymerase I (Pol I)-specific subunit, previously identified as ASE-1 (antisense
      of ERCC1) and as CD3epsilon-associated signal transducer (CAST), and here termed
      CAST or human Pol I-associated factor of 49 kDa (hPAF49), after mouse orthologue
      PAF49. We provide evidence for growth-regulated Tyr phosphorylation of
      CAST/hPAF49, specifically in initiation-competent Pol Ibeta complexes in HeLa
      cells, at a conserved residue also known to be important for signaling during T
      cell activation. CAST/hPAF49 can interact with activator upstream binding factor
      (UBF) and, weakly, with selectivity factor 1 (SL1) at the rDNA (ribosomal DNA
      repeat sequence encoding the 18S, 5.8S, and 28S rRNA genes) promoter. CAST/hPAF49
      specific antibodies and excess CAST/hPAF49 protein, which have no effect on basal
      Pol I transcription, inhibit UBF-activated transcription following functional SL1
      Pol I-rDNA complex assembly and disrupt the interaction of UBF with CAST/hPAF49,
      suggesting that interaction of this Pol I-specific subunit with UBF is crucial
      for activation. Drawing on parallels between mammalian and Saccharomyces
      cerevisiae Pol I transcription machineries, we advance one model for CAST/hPAF49
      function in which the network of interactions of Pol I-specific subunits with UBF
      facilitates conformational changes of the polymerase, leading to stabilization of
      the Pol I-template complex and, thereby, activation of transcription.

PMID- 16809779
TI  - Cyclin D1 determines mitochondrial function in vivo.
AB  - The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that
      phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA
      synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient
      for the development of murine mammary tumors. Herein, cyclin D1 is shown to
      perform a novel function, inhibiting mitochondrial function and size.
      Mitochondrial activity was enhanced by genetic deletion or antisense or small
      interfering RNA to cyclin D1. Global gene expression profiling and functional
      analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics
      demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic
      glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin
      D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and
      mitochondrial function.

PMID- 16809780
TI  - Cell cycle-dependent regulation of Saccharomyces cerevisiae donor preference
      during mating-type switching by SBF (Swi4/Swi6) and Fkh1.
AB  - Saccharomyces mating-type switching occurs through a double-strand break
      initiated gene conversion event at MAT, using one of two donors located distantly
      on the same chromosome, HMLalpha and HMRa. MATa cells preferentially choose
      HMLalpha, a decision that depends on the recombination enhancer (RE) that
      controls recombination along the left arm of chromosome III. We previously showed
      that an fhk1Delta mutation reduces HMLalpha usage in MATa cells, but not to the
      level seen when RE is deleted. We now report that donor preference also depends
      on binding of the Swi4/Swi6 (SBF) transcription factors to an evolutionarily
      conserved SCB site within RE. As at other SCB-containing promoters, SBF binds to
      RE in the G(1) phase. Surprisingly, Fkh1 binds to RE only in G(2), which
      contrasts with its cell cycle-independent binding to its other target promoters.
      SBF and Fkh1 define two independent RE activation pathways, as deletion of both
      Fkh1 and SCB results in nearly complete loss of HML usage in MATa cells. These
      transcription factors create an epigenetic modification of RE in a fashion that
      apparently does not involve transcription. In addition, the putative helicase
      Chl1, previously involved in donor preference, functions in the SBF pathway.

PMID- 16809781
TI  - Spatial localization of m-calpain to the plasma membrane by phosphoinositide
      biphosphate binding during epidermal growth factor receptor-mediated activation.
AB  - Calpain activity is required for de-adhesion of the cell body and rear to enable
      productive locomotion of adherent cells during wound repair and tumor invasion.
      Growth factors activate m-calpain (calpain 2, CAPN2) via ERK/mitogen-activated
      protein kinases, but only when these kinases are localized to the plasma
      membrane. We thus hypothesized that m-calpain is activated by epidermal growth
      factor (EGF) only when it is juxtaposed to the plasma membrane secondary to
      specific docking. Osmotic disruption of NR6 fibroblasts expressing the EGF
      receptor demonstrated m-calpain being complexed with the substratum-adherent
      membrane with this increasing in an EGF-dependent manner. m-Calpain colocalized
      with phosphoinositide biphosphate (PIP(2)) with exogenous phospholipase C removal
      of phosphoinositides, specifically, PI(4,5)P(2) but not PI(4)P(1) or PIP(3),
      releasing the bound m-calpain. Downregulation of phosphoinositide production by 1
      butanol resulted in diminished PIP(2) in the plasma membrane and eliminated EGF
      induced calpain activation. This PIP(2)-binding capacity resided in domain III of
      calpain, which presents a putative C2-like domain. This active conformation of
      this domain appears to be partially masked in the holoenzyme as both activation
      of m-calpain by phosphorylation at serine 50 and expression of constitutively
      active phosphorylation mimic glutamic acid-increased m-calpain binding to the
      membrane, consistent with blockade of this cascade diminishing membrane
      association. Importantly, we found that m-calpain was enriched toward the rear of
      locomoting cells, which was more pronounced in the plasma membrane footprints;
      EGF further enhanced this enrichment, in line with earlier reports of loss of
      PIP(2) in lamellipodia of motile cells. These data support a model of m-calpain
      binding to PIP(2) concurrent with and likely to enable ERK activation and
      provides a mechanism by which cell de-adhesion is directed to the cell body and
      tail as phospholipase C-gamma hydrolyzes PIP(2) in the protruding lamellipodia.

PMID- 16809782
TI  - Ca2+/calmodulin-dependent protein kinase II is a modulator of CARMA1-mediated NF
      kappaB activation.
AB  - CARMA1 is a central regulator of NF-kappaB activation in lymphocytes. CARMA1 and
      Bcl10 functionally interact and control NF-kappaB signaling downstream of the T
      cell receptor (TCR). Computational analysis of expression neighborhoods of CARMA1
      Bcl10MALT 1 for enrichment in kinases identified calmodulin-dependent protein
      kinase II (CaMKII) as an important component of this pathway. Here we report that
      Ca(2+)/CaMKII is redistributed to the immune synapse following T-cell activation
      and that CaMKII is critical for NF-kappaB activation induced by TCR stimulation.
      Furthermore, CaMKII enhances CARMA1-induced NF-kappaB activation. Moreover, we
      have shown that CaMKII phosphorylates CARMA1 on Ser109 and that the
      phosphorylation facilitates the interaction between CARMA1 and Bcl10. These
      results provide a novel function for CaMKII in TCR signaling and CARMA1-induced
      NF-kappaB activation.

PMID- 16809783
TI  - Functional and physical interaction of yeast Mgs1 with PCNA: impact on RAD6
      dependent DNA damage tolerance.
AB  - Proliferating cell nuclear antigen (PCNA), a sliding clamp required for
      processive DNA synthesis, provides attachment sites for various other proteins
      that function in DNA replication, DNA repair, cell cycle progression and
      chromatin assembly. It has been shown that differential posttranslational
      modifications of PCNA by ubiquitin or SUMO play a pivotal role in controlling the
      choice of pathway for rescuing stalled replication forks. Here, we explored the
      roles of Mgs1 and PCNA in replication fork rescue. We provide evidence that Mgs1
      physically associates with PCNA and that Mgs1 helps suppress the RAD6 DNA damage
      tolerance pathway in the absence of exogenous DNA damage. We also show that PCNA
      sumoylation inhibits the growth of mgs1 rad18 double mutants, in which PCNA
      sumoylation and the Srs2 DNA helicase coordinately prevent RAD52-dependent
      homologous recombination. The proposed roles for Mgs1, Srs2, and modified PCNA
      during replication arrest highlight the importance of modulating the RAD6 and
      RAD52 pathways to avoid genome instability.

PMID- 16809784
TI  - Constitutive ALK5-independent c-Jun N-terminal kinase activation contributes to
      endothelin-1 overexpression in pulmonary fibrosis: evidence of an autocrine
      endothelin loop operating through the endothelin A and B receptors.
AB  - The signal transduction mechanisms generating pathological fibrosis are almost
      wholly unknown. Endothelin-1 (ET-1), which is up-regulated during tissue repair
      and fibrosis, induces lung fibroblasts to produce and contract extracellular
      matrix. Lung fibroblasts isolated from scleroderma patients with chronic
      pulmonary fibrosis produce elevated levels of ET-1, which contribute to the
      persistent fibrotic phenotype of these cells. Transforming growth factor beta
      (TGF-beta) induces fibroblasts to produce and contract matrix. In this report, we
      show that TGF-beta induces ET-1 in normal and fibrotic lung fibroblasts in a Smad
      independent ALK5/c-Jun N-terminal kinase (JNK)/Ap-1-dependent fashion. ET-1
      induces JNK through TAK1. Fibrotic lung fibroblasts display constitutive JNK
      activation, which was reduced by the dual ETA/ETB receptor inhibitor, bosentan,
      providing evidence of an autocrine endothelin loop. Thus, ET-1 and TGF-beta are
      likely to cooperate in the pathogenesis of pulmonary fibrosis. As elevated JNK
      activation in fibrotic lung fibroblasts contributes to the persistence of the
      myofibroblast phenotype in pulmonary fibrosis by promoting an autocrine ET-1
      loop, targeting the ETA and ETB receptors or constitutive JNK activation by
      fibrotic lung fibroblasts is likely to be of benefit in combating chronic
      pulmonary fibrosis.

PMID- 16809787
TI  - Identification of autoantibodies in human plasma recognizing an apoB-100 LDL
      receptor binding site peptide.
AB  - The aim of this study was to test the hypothesis that autoantibodies recognize
      amino acid sequences in the LDL receptor binding region of apolipoprotein B-100
      (apoB-100). Autoantibodies against an unmodified or malondialdehyde (MDA)
      modified LDL receptor binding site peptide were determined by ELISA in baseline
      plasma samples of 78 cases with coronary events and 149 matched controls
      recruited from the prospective Malmo Diet Cancer Study. IgG and IgM recognizing
      this peptide were detected in all subjects but did not differ between cases and
      controls. Inverse associations were observed between IgG against the native
      binding site and plasma oxidized LDL (r = -0.21, P < 0.005), but there were no
      significant associations with total or LDL cholesterol levels. In univariate
      analyses, inverse associations were found between baseline carotid intima-media
      thickness and IgG against the MDA-modified binding site (r = -0.14, P < 0.05),
      but this association was lost when controlling for other major cardiovascular
      risk factors. Specificity studies demonstrated that the binding of autoantibodies
      to these sequences could be inhibited by oxidized but not by native LDL.
      Autoantibodies recognizing the LDL receptor binding site in apoB-100 are
      frequently expressed. Their association with plasma oxidized LDL suggests that
      they have been generated in response to breakdown products of LDL oxidation, but
      their influence on cholesterol metabolism and the development of atherosclerosis
      appears limited.

PMID- 16809786
TI  - Multitasking C2H2 zinc fingers link Zac DNA binding to coordinated regulation of
      p300-histone acetyltransferase activity.
AB  - Zac is a C(2)H(2) zinc finger protein that regulates apoptosis and cell cycle
      arrest through DNA binding and transactivation. The coactivator proteins p300/CBP
      enhance transactivation through their histone acetyltransferase (HAT) activity by
      modulating chromatin structure. Here, we show that p300 increases Zac
      transactivation in a strictly HAT-dependent manner. Whereas the classic
      recruitment model proposes that coactivation simply depends on the capacity of
      the activator to recruit the coactivator, we demonstrate that coordinated binding
      of Zac zinc fingers and C terminus to p300 regulates HAT function by increasing
      histone and acetyl coenzyme A affinities and catalytic activity. This concerted
      regulation of HAT function is mediated via the KIX and CH3 domains of p300 in an
      interdependent manner. Interestingly, Zac zinc fingers 6 and 7 simultaneously
      play key roles in DNA binding and p300 regulation. Our findings demonstrate, for
      the first time, that C(2)H(2) zinc fingers can link DNA binding to HAT signaling
      and suggest a dynamic role for DNA-binding proteins in the enzymatic control of
      transcription.

PMID- 16809785
TI  - Protein composition and electron microscopy structure of affinity-purified human
      spliceosomal B complexes isolated under physiological conditions.
AB  - The spliceosomal B complex is the substrate that undergoes catalytic activation
      leading to catalysis of pre-mRNA splicing. Previous characterization of this
      complex was performed in the presence of heparin, which dissociates less stably
      associated components. To obtain a more comprehensive inventory of the B complex
      proteome, we isolated this complex under low-stringency conditions using two
      independent methods. MS2 affinity-selected B complexes supported splicing when
      incubated in nuclear extract depleted of snRNPs. Mass spectrometry identified
      over 110 proteins in both independently purified B complex preparations,
      including approximately 50 non-snRNP proteins not previously found in the
      spliceosomal A complex. Unexpectedly, the heteromeric hPrp19/CDC5 complex and 10
      additional hPrp19/CDC5-related proteins were detected, indicating that they are
      recruited prior to spliceosome activation. Electron microscopy studies revealed
      that MS2 affinity-selected B complexes exhibit a rhombic shape with a maximum
      dimension of 420 A and are structurally more homogeneous than B complexes treated
      with heparin. These data provide novel insights into the composition and
      structure of the spliceosome just prior to its catalytic activation and suggest a
      potential role in activation for proteins recruited at this stage. Furthermore,
      the spliceosomal complexes isolated here are well suited for complementation
      studies with purified proteins to dissect factor requirements for spliceosome
      activation and splicing catalysis.

PMID- 16809788
TI  - Patients' characteristics and rate of Internet use to obtain cancer information.
AB  - The aim of this study was to present baseline data on the access to Internet by
      French breast cancer patients attending genetic clinics and to examine factors
      affecting Internet health-related use. Twenty-four percent of participants used
      Internet to obtain information about the disease. This rate was higher among
      patients with health occupations [adjusted odds ratio (adjOR) 2.6; 95% confidence
      interval (CI) 1.3-5.1], the most highly educated (adjOR 2.1; 95% CI 1.1-4.0) and
      those under 41 years of age (adjOR 7.3; 95% CI 2.1-26.2). Almost one of every
      three women was dissatisfied of this source of information.

PMID- 16809789
TI  - Using the UK primary care Quality and Outcomes Framework to audit health care
      equity: preliminary data on diabetes management.
AB  - BACKGROUND: The incentivization of UK primary care through the Quality and
      Outcomes Framework (QOF) has released an unprecedented supply of data that in
      theory could aid health equity audit and reduce health inequalities. The current
      system allows for 'exception reporting' whereby patients can be excluded from
      calculation of payment for reasons such as failure to attend review. We
      speculated that such exclusions could be linked to socioeconomic deprivation.
      METHODS: We assessed 'exception reporting' rates for 15 diabetes indicators using
      2004/05 QOF data for 49 general practitioner (GP) practices in Brighton and Hove
      and related it to a deprivation ranking for each practice. RESULTS: The
      standardized diabetes prevalence was 26% higher (P < 0.001) in the highest
      compared to the lowest quintile of deprivation. Correlations between 'exception
      reporting' and deprivation were seen for 10 of the 15 diabetes indicators (r =
      0.20-0.41, P < 0.05). Practices with a more deprived patient population were more
      likely to report 'exceptions' for QOF indicators, although there was no such
      relationship with the achievement of QOF targets. CONCLUSIONS: Strategies to
      reduce health inequalities need to take into account that high levels of
      exception reporting, particularly in practices with deprived populations, may be
      disguising unmet need in those populations.

PMID- 16809790
TI  - A survey of staff attitudes to smoking-related policy and intervention in
      psychiatric and general health care settings.
AB  - BACKGROUND: Although the move to smoke-free hospital settings is generally a
      popular initiative, it may be a more challenging and controversial issue in
      mental health care. A survey was carried out to investigate differences in
      attitudes between clinical staff in psychiatric and general medical settings to
      smoke-free policy and intervention. METHOD: The sample comprised 2574 NHS staff
      working in two Acute Hospital Trusts and one Mental Health Trust in England.
      Attitudes were examined on two factors: health care settings as smoke-free
      environments and the role of staff in stop smoking intervention. RESULTS: The
      findings indicated that attitudes on the two factors were only moderately
      correlated. Psychiatric staff expressed significantly less favourable attitudes
      than general staff to smoke-free health care settings and also to the role of
      staff in stop smoking intervention. The largest difference between the settings
      concerned the implementation of smoking bans. While approximately 1 in 10 staff
      in the general setting disagreed with a smoking ban in their wards or clinics,
      nearly one in three psychiatric staff was against such a ban in their setting.
      CONCLUSIONS: Staff attitudes need to be carefully considered, particularly in
      psychiatric settings, in attempts to implement smoke-free policies in health care
      settings.

PMID- 16809791
TI  - A Delphi-based consensus study into planning for biological incidents.
AB  - OBJECTIVE: Biological incidents present a significant threat to health services
      in the UK. The objective of this study was to achieve consensus in all phases of
      biological incident planning and response. METHODS: A three-round Delphi study
      was conducted using a panel of 23 experts from specialities involved in the
      management of biological incidents. The consensus and non-consensus outcomes from
      the Delphi study were subsequently presented for discussion in four syndicate
      groups at a one-day consensus conference funded by the Health Protection Agency.
      RESULTS: The results of each syndicate group discussion were presented at a
      subsequent plenary session at the end of the conference. Further iteration of
      both the consensus and the non-consensus outcomes of the Delphi study resulted in
      the endorsement, modification, integration or rejection of individual statements.
      125 consensus statements were produced. CONCLUSIONS: The 125 synopsis consensus
      statements that all phases of biological incident planning and response. These
      can be used to inform policy decisions and translated into practical guidance for
      emergency planners and first responders at local, regional and national levels.

PMID- 16809792
TI  - Pain and overall health status in older people with hip and knee replacement: a
      population perspective.
AB  - OBJECTIVE: To investigate the health-related quality of life and presence of hip
      or knee pain according to whether or not people had had previous hip or knee
      arthroplasty. STUDY DESIGN AND SETTING: Cross-sectional survey representing
      randomly selected sample of 5500 elderly (65+) people. Pain prevalence rates
      obtained from standard screening questions. Standard pain severity ratings
      obtained for each hip and knee. RESULTS: People with a past arthroplasty had
      worse health status compared to other people (p < 0.001 for all but two SF-36
      dimensions). Hip or knee pain was more prevalent amongst people with past hip or
      knee replacement than amongst those without (62.5% versus 36.5% respectively;
      following adjustment for age and sex: Mantel-Haenszel combined odds ratio = 2.90,
      95% CI 2.30-3.68, p < 0.001). More replaced knee joints were symptomatic than
      replaced hip joints (OR = 1.62, p = 0.022). CONCLUSIONS: Elderly people with a
      past hip or knee arthroplasty have significantly greater health and social care
      needs than other people--especially those related to pain and mobility. This may
      reflect the generalised nature of the underlying disease process.

PMID- 16809793
TI  - Predictors of interest in nutrition topics and willingness to participate in
      local nutrition programmes.
AB  - OBJECTIVE: To investigate the predictors of interest in nutrition topics and
      willingness to participate in weight management courses and nutrition-related
      chronic disease management courses. METHODS: Data from a cross-sectional survey
      (n = 1007 Koreans aged >or=30) on nutrition-related conditions, nutrition
      behaviours, interest in nutrition topics and willingness to participate in two
      types of nutrition education courses, and general characteristics. Binary
      logistic regression was used to identify predictors of the participants' interest
      in the topic and willingness to participate. RESULTS: Younger, richer and more
      educated participants were significantly more likely to be willing to participate
      in 'nutrition-related chronic disease management'. Having a higher income and
      being male increased the odds of being interested in this topic. Younger, more
      obese, high-income females and those interested to keep their weight and reduce
      fatty foods were more likely to be willing to participate in 'weight management'.
      CONCLUSION: There is a need to increase awareness about the link between
      nutrition and related health problems, especially regarding 'hidden' health
      problems to tailor the programmes especially for older, low-income and less
      educated people and to focus on increasing their interest in nutrition topics.

PMID- 16809794
TI  - Treatment of pediatric overweight: an examination of feasibility and
      effectiveness in an applied clinical setting.
AB  - OBJECTIVE: To examine the effectiveness and feasibility of an evidence-based
      treatment for weight loss in children. METHODS: A total of 41 children who were
      overweight and their families were provided a modified version of the Traffic
      Light Diet (TLD) in an applied setting. Children who received treatment as usual
      (TAU) constituted a comparison sample. RESULTS: Children receiving the modified
      TLD demonstrated a significantly greater reduction in standardized body mass
      index (z-BMI) than children receiving TAU. CONCLUSIONS: The TLD is a feasible
      treatment that can be implemented in applied settings that include samples often
      excluded from treatment efficacy studies. Results are discussed in the context of
      bridging the gap between science and service.

PMID- 16809797
TI  - Pharmacokinetics and safety profile of ispronicline (TC-1734), a new brain
      nicotinic receptor partial agonist, in young healthy male volunteers.
AB  - Recent research suggests that drugs activating nicotine acetylcholine receptors
      might be promising therapy in cognitive decline seen in the elderly, including
      Alzheimer's disease. Ispronicline (TC-1734), a brain-selective alpha4beta2
      nicotine acetylcholine receptor partial agonist, has shown memory-enhancing
      properties in rodents and a good tolerability profile. The safety and the full
      pharmacokinetic profile of TC-1734 and its N-desalkylated metabolite, TC-1784,
      were investigated in 2 phase I studies, and results are reported in this article.
      Study A used a double-blind, placebo-controlled, crossover design with a rising
      single-dose scheme (2-320 mg). Study B used a double-blind, placebo-controlled,
      parallel-group design with a rising multiple-dose scheme (doses: 50, 100, and 200
      mg, once daily, x 10 days). Cmax of TC-1734 was reached around 1 to 2 hours
      postdose, and mean terminal half-life (t1/2) ranged from 3 to 5.3 hours (single
      doses) and from 2.7 to 8.8 hours (repeated doses). No accumulation of TC-1734 was
      observed after 10 days. Renal clearance appeared to be a minor method of
      elimination of TC-1734 and TC-1784. A high interindividual variability was noted
      for all parameters. Across the dose ranges explored, TC-1734 was safe and well
      tolerated. No changes of clinical significance were seen on laboratory and
      cardiovascular parameters. Adverse events were generally of mild to moderate
      intensity, with dizziness and headache being reported most frequently.

PMID- 16809798
TI  - Pharmacokinetics and urinary excretion of vincristine sulfate liposomes injection
      in metastatic melanoma patients.
AB  - Vincristine sulfate liposomes injection (VSLI) is a liposomal formulation of
      vincristine encapsulated in sphingosomes composed of sphinogomyelin and
      cholesterol (58/42; mol/mol). The pharmacokinetics and urinary excretion of VSLI
      were evaluated in 12 patients with metastatic melanoma after single-dose (2.0
      mg/m2 every 2 weeks = 1 cycle) and multiple-dose (cycle 3, pharmacokinetics only)
      administrations (intravenous infusion over 1 hour). After VSLI infusion, total
      (released and encapsulated) vincristine concentrations in plasma remained
      relatively constant for 3 to 12 hours and thereafter declined, with interpatient
      variability seen in the rate of decline resulting in monoexponential or
      biexponential profiles. The area under the plasma concentration-time curve from
      time zero to infinity of total vincristine in plasma ranged from 4933 to 40495
      h.ng/mL and total clearance ranged from 131 to 445 mL/h. The volume of
      distribution at steady state was 2650 +/- 731 mL, indicating VSLI was mainly
      confined within the plasma. The released vincristine concentrations in plasma
      were below the level of quantitation in 95% of samples. The pharmacokinetic
      parameters were similar between cycles 1 and 3, and trough plasma levels of total
      vincristine were below the level of quantitation of 1 ng/mL. Approximately 8% of
      the injected dose was excreted in the urine as unchanged vincristine (7%) or N
      desformylvincristine (0.8%). Overall, VSLI exhibited a longer circulation half
      life and higher area under the plasma concentration-time curve compared to
      conventional vincristine, whereas its route of elimination remained unchanged.

PMID- 16809799
TI  - Absolute bioavailability and disposition of lanthanum in healthy human subjects
      administered lanthanum carbonate.
AB  - Lanthanum carbonate [La2(CO3)3] is a noncalcium, non-aluminum phosphate binder
      indicated for hyperphosphatemia treatment in end-stage renal disease. A
      randomized, open-label, parallel-group, phase I study was conducted to determine
      absolute bioavailability and investigate excretory routes for systemic lanthanum
      in healthy subjects. Twenty-four male subjects were randomized to a single
      lanthanum chloride (LaCl3) intravenous infusion (120 microg elemental lanthanum
      over a 4-hour period), a single 1-g oral dose [chewable La2(CO3)3 tablets; 4 x
      250 mg elemental lanthanum], or no treatment (control). Serial blood, urine, and
      fecal samples were collected for 7 days postdosing. The absolute bioavailability
      of lanthanum [administered as La2(CO3)3] was extremely low (0.00127% +/-
      0.00080%), with individual values in the range of 0.00015% to 0.00224%. Renal
      clearance was negligible following oral administration (1.36 +/- 1.43 mL/min).
      Intravenous administration confirmed low renal clearance (0.95 +/- 0.60 mL/min),
      just 1.7% of total plasma clearance. Fecal lanthanum excretion was not
      quantifiable after intravenous administration owing to high and variable
      background fecal lanthanum and constraints on the size of the intravenous dose.
      These findings demonstrate that lanthanum absorption from the intestinal tract
      into the systemic circulation is extremely low and that absorbed drug is cleared
      predominantly by nonrenal mechanisms.

PMID- 16809800
TI  - Pharmacokinetic/pharmacodynamic modeling of pegfilgrastim in healthy subjects.
AB  - This analysis was conducted to characterize the pharmacokinetics and
      pharmacodynamics of pegfilgrastim and to develop a pharmacokinetic
      pharmacodynamic model to describe the granulopoietic effects of pegfilgrastim and
      the homeostatic regulation of pegfilgrastim clearance in healthy subjects.
      Pegfilgrastim serum concentration data and differential white cell counts were
      obtained from an open-label, single-dose, dose escalation study. Healthy subjects
      (8 subjects/dose group) received a single subcutaneous dose of 30, 60, 100, or
      300 microg/kg pegfilgrastim. Pegfilgrastim exhibited nonlinear pharmacokinetics;
      clearance decreased with increasing dose. A dose-dependent increase in absolute
      neutrophil count with an increase in the percentage of band cells was observed. A
      pharmacokinetic-pharmacodynamic model was developed that adequately described the
      nonlinear pharmacokinetics of pegfilgrastim, feedback regulation of pegfilgrastim
      clearance by neutrophils, and the differential effects of pegfilgrastim on
      neutrophil populations in blood.

PMID- 16809801
TI  - Time-dependent interaction between lopinavir/ritonavir and fexofenadine.
AB  - This study investigated the effect of single-dose and steady-state
      lopinavir/ritonavir on the exposure to fexofenadine, as a measure of P
      glycoprotein activity. Sixteen volunteers (8 women) received single-dose oral
      fexofenadine 120 mg alone, in combination with single-dose ritonavir 100 mg or
      lopinavir/ritonavir 400/100 mg (randomized 1:1, stratified by sex), and in
      combination with steady-state lopinavir/ritonavir 400/100 mg twice daily. Single
      dose ritonavir and lopinavir/ritonavir increased the area under the fexofenadine
      plasma concentration-time curve from 0 to infinity (AUC(infinity)) by 2.2- and
      4.0-fold, respectively (P < .02). Steady-state lopinavir/ritonavir increased the
      fexofenadine AUC(infinity) by 2.9-fold. No changes were observed in the
      fexofenadine elimination half-life (P > .12). The fexofenadine AUC(infinity) was
      increased by lopinavir/ritonavir, likely due to increased bioavailability
      secondary to P-glycoprotein inhibition. After repeated administration of
      lopinavir/ritonavir, the interaction was attenuated compared to the single-dose
      effect, although a net inhibitory effect was maintained. Time-dependent
      inhibition of P-glycoprotein by lopinavir/ritonavir should be considered when P
      glycoprotein substrates are coadministered.

PMID- 16809803
TI  - Predictive power of an in vitro system to assess drug interactions of an
      antimuscarinic medication: a comparison of in vitro and in vivo drug-drug
      interaction studies of trospium chloride with digoxin.
AB  - The authors studied a potential drug-drug interaction via findings from in vitro
      and in vivo studies, to assess whether the in vitro system was predictive of in
      vivo clinical pharmacokinetic outcomes. An in vitro experiment and a clinical
      study were performed to assess the potential for interaction. The effect of
      trospium chloride on human P-glycoprotein-mediated transport of [3H]-digoxin was
      determined in vitro. A randomized, crossover clinical trial in 40 subjects was
      performed to evaluate the effect of trospium on the pharmacokinetics of digoxin
      in vivo. The findings from the studies were then compared. The in vitro findings
      in this study were corroborated by the clinical study via assessment of
      inhibition and impact on pharmacokinetic parameters. The in vitro system for
      assessment of a potential interaction of 2 drugs excreted primarily through the
      kidney was predictive of the pharmacokinetic outcomes obtained from a clinical
      setting.

PMID- 16809802
TI  - Drug-drug interaction after single oral doses of the furanocoumarin methoxsalen
      and cyclosporine.
AB  - Furanocoumarins increase the bioavailability of drugs that are CYP3A4 substrates.
      A possible interaction of methoxsalen with cyclosporine was evaluated in 12
      healthy volunteers following oral administration of 40 mg methoxsalen, 200 mg
      cyclosporine, or a combination of both in a randomized crossover study.
      Methoxsalen increased area under the plasma concentration-time curve (AUC) and
      peak plasma concentration (Cmax) of cyclosporine by 29% (range, -20% to 172%; P <
      .05) and 8% (range, -10% to 26%; P < .05), respectively, compared to cyclosporine
      alone. The AUC geometric means ratio (95% confidence interval) for cyclosporine
      plus methoxsalen/cyclosporine alone was 1.14 (1.02, 1.27), and treatments were
      therefore not bioequivalent. Methoxsalen causes a clinically significant
      interaction with cyclosporine in some susceptible individuals. The reasons for
      susceptibility and the clinical implications for chronic cyclosporine
      administration have not been established. Caution is recommended in combination
      therapy, and more frequent monitoring of cyclosporine plasma levels and clinical
      monitoring is advised.

PMID- 16809804
TI  - Study of the pharmacokinetic interaction between simvastatin and prescription
      omega-3-acid ethyl esters.
AB  - The coadministration of prescription omega-3-acid ethyl esters (P-OM3) with a
      statin may present a treatment option for patients with mixed hyperlipidemia.
      This open-label, randomized, 2-way crossover, drug-drug interaction study
      evaluated the impact of P-OM3 capsules on plasma simvastatin pharmacokinetics in
      24 healthy volunteers. Under fasted conditions, 80 mg simvastatin was
      administered with or without 4 g P-OM3 for two 14-day periods. After 14 days of
      dosing to achieve steady state, no significant differences were found in either
      the extent (AUC(tau)) or rate (Cmax) of exposure to simvastatin or its major beta
      hydroxy metabolite after coadministration of P-OM3 with simvastatin compared with
      administration of simvastatin alone. At steady state, the coadministration of P
      OM3 capsules did not appear to affect the pharmacokinetics of simvastatin
      tablets. The combination of P-OM3 capsules and simvastatin appeared to be well
      tolerated.

PMID- 16809806
TI  - Discordance between N-acetyltransferase 2 phenotype and genotype in a population
      of Hmong subjects.
AB  - Polymorphisms of N-acetyltransferase 2 (NAT2) acetylation may influence drug
      toxicities and efficacy and are associated with a differential susceptibility to
      select cancers. Acetylation phenotype may have clinical implications. The
      purposes of this study were to determine the genetic basis of an apparent
      predominance of slow acetylation phenotype and to assess concordance with
      genotype in a population of Hmong residing in Minnesota. Urine and DNA obtained
      from unrelated Hmong 18 to 65 years of age were used to determine phenotype from
      caffeine metabolites, whereas direct nucleotide sequencing of the NAT2 coding
      region, followed by cloning, identified all known allelic variants. From 61
      subjects (27 men, 30 +/- 11 years), analysis of 50 urine-DNA pairs identified 46
      (92%) slow acetylators and 4 (8%) rapid acetylators by phenotype. Genotypic
      analysis inferred 5 (10%) slow acetylators and 45 (90%) rapid acetylators. There
      is 86% discordance between phenotype and genotype. A predominance of NAT2 slow
      acetylation phenotype in the Hmong is confirmed, and a significant discordance
      between NAT2 phenotype and genotype is identified. In this population, slow
      acetylation phenotype determined by a metabolic probe would not have been
      predicted by genotype alone. Environmental, genetic, or phenotypic anomalies that
      may contribute to this discordance should be considered and evaluated in future
      studies within this unique population.

PMID- 16809805
TI  - Lack of effect of aprepitant on hydrodolasetron pharmacokinetics in CYP2D6
      extensive and poor metabolizers.
AB  - To prevent chemotherapy-induced nausea and vomiting, aprepitant is given with a
      corticosteroid and a 5-hydroxytryptamine type 3 antagonist, such as dolasetron.
      Dolasetron is converted to the active metabolite hydrodolasetron, which is
      cleared largely via CYP2D6. The authors determined whether aprepitant, a moderate
      CYP3A4 inhibitor, alters hydrodolasetron pharmacokinetics in CYP2D6 poor and
      extensive metabolizers. Six CYP2D6 poor and 6 extensive metabolizers were
      randomized in an open-label, crossover fashion to treatment A (dolasetron 100 mg
      on day 1) and treatment B (dolasetron 100 mg plus aprepitant 125 mg on day 1,
      aprepitant 80 mg on days 2-3). For hydrodolasetron area under the concentration
      versus-time curve (AUC0-infinity) and peak plasma concentration (Cmax), geometric
      mean ratios (B/A) and 90% confidence intervals (CIs) fell below the predefined
      limit (2.0) for clinical significance (AUC0-infinity, 1.09 [90% CI, 1.01-1.18],
      Cmax, 1.08 [90% CI, 0.94-1.24]). Aprepitant did not affect the pharmacokinetics
      of hydrodolasetron, regardless of CYP2D6 metabolizer type, and was generally well
      tolerated when coadministered with dolasetron in volunteers.

PMID- 16809807
TI  - High-dose statin treatment does not alter plasma marker for brain cholesterol
      metabolism in patients with moderately elevated plasma cholesterol levels.
AB  - Statins inhibit endogenous cholesterol synthesis, up-regulate low-density
      lipoprotein (LDL) receptor expression in mammalian liver cells, and thus decrease
      circulating LDL-cholesterol concentrations. As cholesterol seems to play a role
      in the development of neurodegenerative diseases, it is of interest to evaluate
      the effect of high dosages of statins (eg, atorvastatin or simvastatin) on brain
      cholesterol metabolism. Plasma samples from 44 participants (aged 30-69 years, 16
      men and 18 women) of an earlier randomized, placebo-controlled, double-blind
      trial, who took 40 mg atorvastatin or 80 mg simvastatin daily for 2 months, were
      used to analyze total cholesterol, its precursor lathosterol, and its metabolites
      24(S)-hydroxycholesterol and 27-hydroxycholesterol. Despite a significant
      decrease in absolute plasma concentrations of oxysterols, total cholesterol, and
      its endogenous synthesis rate, indicated by a decreased ratio of lathosterol to
      cholesterol, the plasma 24(S)-hydroxycholesterol to cholesterol ratio, a
      surrogate marker of brain cholesterol homeostasis, remained unchanged. Short-term
      high-dose atorvastatin and simvastatin treatment does not seem to influence brain
      cholesterol metabolism in patients with moderately elevated plasma cholesterol
      levels.

PMID- 16809810
TI  - Pharmacology of acetylcholinesterase inhibitors and N-methyl-D-aspartate
      receptors for combination therapy in the treatment of Alzheimer's disease.
AB  - The search for effective treatments of Alzheimer's disease (AD) is one of the
      major challenges facing modern medicine. Acetylcholinesterase (AChE) inhibitors
      (AChEIs) are effective for the treatment of mild to moderate AD, and memantine,
      an N-methyl-D-aspartate (NMDA) inhibitor, has been approved for moderate to
      severe AD. Galantamine is of particular interest because it has a dual mechanism
      of action: it is postulated to be both an AChEI and an allosteric modulator of
      nicotinic receptors. Modulation of NMDA and nicotinic receptors by memantine and
      galantamine may provide an optimal combination therapy for AD. The cholinergic
      and glutamatergic neurotransmitter systems, which share a close functional
      relationship, may play a role in the pathogenesis of AD. Close examination of the
      pharmacology of the 2 compounds suggests that galantamine can augment memantine's
      glutamatergic noise suppression while simultaneously enhancing the physiologic
      glutamatergic signal. The link between these systems suggests that AD therapies,
      which capitalize on this relationship, may be more effective in improving
      cognition than approaches focusing on a single system.

PMID- 16809811
TI  - Rationale for combination therapy with galantamine and memantine in Alzheimer's
      disease.
AB  - A combination of cholinergic and glutamatergic dysfunction appears to underlie
      the symptomatology of Alzheimer's disease. Therefore, one hypothesis is that
      treatment strategies should address impairments in both systems. Galantamine is
      an acetylcholinesterase inhibitor that, unlike other acetylcholinesterase
      inhibitors, has a postulated dual mode of action as a nicotinic receptor
      modulator. Galantamine has demonstrated long-term efficacy in improving or
      maintaining cognition, functionality, and behavior in patients with mild to
      moderate Alzheimer's disease. Memantine, a noncompetitive N-methyl-D-aspartate
      receptor antagonist, reduces deterioration in cognition and function in patients
      with moderate to severe Alzheimer's disease. Pharmacokinetic and pharmacodynamic
      as well as ongoing observation studies support the concept of adjunctive therapy
      with memantine in patients with advanced moderate Alzheimer's disease currently
      treated with an established galantamine regimen. The potential to modulate both
      acetylcholine and glutamate pathways in Alzheimer's disease presents a novel
      treatment strategy for the management of mild to moderately severe Alzheimer's
      disease.

PMID- 16809814
TI  - Osmogenetics: Aristotle to Arabidopsis.

PMID- 16809815
TI  - Structural study of elements of Tetrahymena telomerase RNA stem-loop IV domain
      important for function.
AB  - Tetrahymena telomerase RNA (TER) contains several regions in addition to the
      template that are important for function. Central among these is the stem-loop IV
      domain, which is involved in both catalysis and RNP assembly, and includes
      binding sites for both the holoenzyme assembly protein p65 and telomerase reverse
      transcriptase (TERT). Stem-loop IV contains two regions with high evolutionary
      sequence conservation: a central GA bulge between helices, and a terminal loop.
      We solved the solution structure of loop IV and modeled the structure of the
      helical region containing the GA bulge, using NMR and residual dipolar couplings.
      The central GA bulge with flanking C-G base pairs induces a approximately 50
      degrees semi-rigid bend in the helix. Loop IV is highly structured, and contains
      a conserved C-U base pair at the top of the helical stem. Analysis of new and
      previous biochemical data in light of the structure provides a rationale for some
      of the sequence conservation in this region of TER. The results suggest that
      during holoenzyme assembly the protein p65 recognizes a bend in stem IV, and this
      binding to central stem IV helps to position the structured loop IV for
      interaction with TERT and other region(s) of TER.

PMID- 16809816
TI  - Structure-function analysis of Plasmodium RNA triphosphatase and description of a
      triphosphate tunnel metalloenzyme superfamily that includes Cet1-like RNA
      triphosphatases and CYTH proteins.
AB  - RNA triphosphatase catalyzes the first step in mRNA capping. The RNA
      triphosphatases of fungi and protozoa are structurally and mechanistically
      unrelated to the analogous mammalian enzyme, a situation that recommends RNA
      triphosphatase as an anti-infective target. Fungal and protozoan RNA
      triphosphatases belong to a family of metal-dependent phosphohydrolases
      exemplified by yeast Cet1. The Cet1 active site is unusually complex and located
      within a topologically closed hydrophilic beta-barrel (the triphosphate tunnel).
      Here we probe the active site of Plasmodium falciparum RNA triphosphatase by
      targeted mutagenesis and thereby identify eight residues essential for catalysis.
      The functional data engender an improved structural alignment in which the
      Plasmodium counterparts of the Cet1 tunnel strands and active-site functional
      groups are located with confidence. We gain insight into the evolution of the
      Cet1-like triphosphatase family by noting that the heretofore unique tertiary
      structure and active site of Cet1 are recapitulated in recently deposited
      structures of proteins from Pyrococcus (PBD 1YEM) and Vibrio (PDB 2ACA). The
      latter proteins exemplify a CYTH domain found in CyaB-like adenylate cyclases and
      mammalian thiamine triphosphatase. We conclude that the tunnel fold first
      described for Cet1 is the prototype of a larger enzyme superfamily that includes
      the CYTH branch. This superfamily, which we name "triphosphate tunnel
      metalloenzyme," is distributed widely among bacterial, archaeal, and eukaryal
      taxa. It is now clear that Cet1-like RNA triphosphatases did not arise de novo in
      unicellular eukarya in tandem with the emergence of caps as the defining feature
      of eukaryotic mRNA. They likely evolved by incremental changes in an ancestral
      tunnel enzyme that conferred specificity for RNA 5'-end processing.

PMID- 16809817
TI  - A three-hybrid screen identifies mRNAs controlled by a regulatory protein.
AB  - RNA-protein interactions are important in many biological contexts.
      Identification of the networks that connect regulatory proteins to one another
      and to the mRNAs they control is a critical need. Here, we use a yeast three
      hybrid screening approach to identify RNAs that bind a known RNA regulatory
      protein, the Saccharomyces cerevisiae PUF protein, Mpt5p. The assay selects RNAs
      that bind in vivo using simple phenotypes and reporter genes. It enables rapid
      analyses of the affinity and specificity of the interaction. We show that the
      method identifies mRNAs that are genuinely regulated by the protein in vivo, and
      that it complements biochemical strategies, yielding a set of mRNAs that overlap
      with, but are distinct from, those obtained by biochemical means. The approach we
      describe facilitates construction of protein-RNA linkage maps.

PMID- 16809818
TI  - Polyamine-regulated unproductive splicing and translation of spermidine/spermine
      N1-acetyltransferase.
AB  - Spermidine/spermine N1-acetyltransferase (SSAT), the rate-controlling enzyme in
      the interconversion of spermidine and spermine, is regulated by polyamines and
      their analogs at many levels of gene expression. Recently, SSAT pre-mRNA has been
      shown to undergo alternative splicing by inclusion of an exon that contains
      premature termination codons. In the present study, we show that alterations in
      the intracellular polyamine level resulted in a change in the relative abundance
      of SSAT transcripts. Addition of polyamines or their N-diethylated analogs
      reduced the amount of the variant transcript, whereas polyamine depletion by 2
      difluoromethylornithine or MG-132 enhanced the exon inclusion. Experiments
      performed with protein synthesis inhibitors and siRNA-mediated down-regulation of
      Upf1 protein verified that the variant transcript was degraded by nonsense
      mediated mRNA decay (NMD). Interestingly, several proteins have been shown to
      regulate their expression by alternative splicing-coupled NMD, termed regulated
      unproductive splicing and translation (RUST). Our present results suggest that in
      the case of SSAT, RUST is mediated by polyamines, and this system functions to
      fine-tune the polyamine metabolism.

PMID- 16809819
TI  - Conventional 3' end formation is not required for NMD substrate recognition in
      Saccharomyces cerevisiae.
AB  - The recognition and rapid degradation of mRNAs with premature translation
      termination codons by the nonsense-mediated pathway of mRNA decay is an important
      RNA quality control system in eukaryotes. In mammals, the efficient recognition
      of these mRNAs is dependent upon exon junction complex proteins deposited on the
      RNA during pre-mRNA splicing. In yeast, splicing does not play a role in
      recognition of mRNAs that terminate translation prematurely, raising the
      possibility that proteins deposited during alternative pre-mRNA processing events
      such as 3' end formation might contribute to the distinction between normal and
      premature translation termination. We have utilized mRNAs with a 3' poly(A) tail
      generated by ribozyme cleavage to demonstrate that the normal process of 3' end
      cleavage and polyadenylation is not required for mRNA stability or the detection
      of a premature stop codon. Thus, in yeast, the distinction between normal and
      premature translation termination events is independent of both splicing and
      conventional 3' end formation.

PMID- 16809820
TI  - Avian influenza H5N1 detected in German poultry and a United Kingdom wild bird.

PMID- 16809821
TI  - Outbreak of haemolytic uraemic syndrome in Norway: update.

PMID- 16809822
TI  - Measles outbreak in Germany: update.

PMID- 16809823
TI  - Seasonal influenza activity for 2005-2006 season seems to be ending in most
      European countries.

PMID- 16809824
TI  - Rise in antimicrobial resistance in invasive isolates of Escherichia coli and
      Enterococcus faecium in Ireland.

PMID- 16809825
TI  - H5N1 infections in cats--public health implications.

PMID- 16809826
TI  - Influenza update: no new animal H5N1 infections reported in European Union this
      week, and animal and human infections continue to be reported elsewhere.

PMID- 16809827
TI  - Flooding in Europe: a brief review of the health risks.

PMID- 16809828
TI  - Imported cases of chikungunya in metropolitan France, April 2005 - February 2006.

PMID- 16809829
TI  - First results of the active surveillance of Listeria monocytogenes infections in
      the Netherlands reveal higher than expected incidence.

PMID- 16809830
TI  - Different approaches to gathering epidemic intelligence in Europe.

PMID- 16809831
TI  - Preparations for infectious disease surveillance during the football World Cup
      tournament, Germany 2006.

PMID- 16809832
TI  - Limitations of recently published review of national influenza pandemic plans in
      Europe.

PMID- 16809833
TI  - Punnett and duck genetics.

PMID- 16809834
TI  - Note on a sex-linked down character in ducks. 1932.

PMID- 16809835
TI  - Phenotypic plasticity of body size in a temperate population of Drosophila
      melanogaster: when the temperature-size rule does not apply.
AB  - A natural population of Drosophila melanogaster in southern France was sampled in
      three different years and 10 isofemale lines were investigated from each sample.
      Two size-related traits, wing and thorax length, were measured and the
      wing/thorax ratio was also calculated. Phenotypic plasticity was analysed after
      development at seven different constant temperatures, ranging from 12 degrees C
      to 31 degrees C. The three year samples exhibited similar reaction norms,
      suggesting a stable genetic architecture in the natural population. The whole
      sample (30 lines) was used to determine precisely the shape of each reaction
      norm, using a derivative analysis. The practical conclusion was that polynomial
      adjustments could be used in all cases, but with different degrees: linear for
      the wing/thorax ratio, quadratic for thorax length, and cubic for wing length.
      Both wing and thorax length exhibited concave reaction norms, with a maximum
      within the viable thermal range. The temperatures of the maxima were, however,
      quite different, around 15 degrees C for the wing and 19.5 degrees C for the
      thorax. Assuming that thorax length is a better estimate of body size, it is not
      possible to state that increasing the temperature results in monotonically
      decreasing size (the temperature-size rule), although this is often seen to be
      the case for genetic variations in latitudinal clines. The variability of the
      traits was investigated at two levels-within and between lines-and expressed as a
      coefficient of variation. The within-line (environmental) variability revealed a
      regular, quadratic convex reaction norm for the three traits, with a minimum
      around 21 degrees C. This temperature of minimum variability may be considered as
      a physiological optimum, while extreme temperatures are stressful. The between
      line (genetic) variability could also be adjusted to quadratic polynomials, but
      the curvature parameters were not significant. Our results show that the mean
      values of the traits and their variance are both plastic, but react in different
      ways along a temperature gradient. Extreme low or high temperatures decrease the
      size but increase the variability. These effects may be considered as a
      functional response to environmental stress.

PMID- 16809836
TI  - Introgressive hybridization and evolution of a novel protein phenotype: glue
      protein profiles in the nasuta-albomicans complex of Drosophila.
AB  - Glue proteins are tissue-specific proteins synthesized by larval salivary gland
      cells of Drosophila. In Drosophila nasuta nasuta and D. n. albomicans of the
      nasuta subgroup, the genes that encode the major glue protein fractions are X
      linked. In the present study, these X-linked markers have been employed to trace
      the pattern of introgression of D. n. nasuta and D. n. albomicans genomes with
      respect to the major glue protein fractions in their interracial hybrids, called
      cytoraces. These cytoraces have inherited the chromosomes of both parents and
      have been maintained in the laboratory for over 400-550 generations. The analysis
      has revealed that cytoraces with D. n. albomicans X chromosome show either D. n.
      nasuta pattern or a completely novel pattern of glue protein fractions. Further,
      quantitative analysis also shows lack of correlation between the chromosomal
      pattern of inheritance and overall quantity of the major glue protein fractions
      in the cytoraces. Thus, in cytoraces the parental chromosomes are not just
      differentially represented but there is evidence for introgression even at the
      gene level.

PMID- 16809837
TI  - Molecular phylogeny of silk-producing insects based on 16S ribosomal RNA and
      cytochrome oxidase subunit I genes.
AB  - We have examined the molecular-phylogenetic relationships between nonmulberry and
      mulberry silkworm species that belong to the families Saturniidae, Bombycidae and
      Lasiocampidae using 16S ribosomal RNA (16S rRNA) and cytochrome oxidase subunit I
      (coxI) gene sequences. Aligned nucleotide sequences of 16S rRNA and coxI from 14
      silk-producing species were used for construction of phylogenetic trees by
      maximum likelihood and maximum parsimony methods. The tree topology on the basis
      of 16S rRNA supports monophyly for members of Saturniidae and Bombycidae.
      Weighted parsimony analysis weighted towards transversions relative to
      transitions (ts, tv4) for coxI resulted in more robust bootstrap support over
      unweighted parsimony and favours the 16S rRNA tree topology. Combined analysis
      reflected clear biogeographic pattern, and agrees with morphological and
      cytological data.

PMID- 16809838
TI  - Karyotypic differences and evolutionary tendencies of some species from the
      subgenus Obliquodesmus Mlad. of genus Scenedesmus Meyen (Chlorophyta,
      Chlorococcales).
AB  - Karyotype structures of Scenedesmus acuminatus (Lagerch.) Chod. and Scenedesmus
      pectinatus Meyen are compared. The karyotype of S. acuminatus (n = 5) is
      described for the first time. It reveals four large metacentric and one large
      submetacentric chromosomes (4M + 1SM). The established karyotype differences have
      been helpful in clarifying the taxonomic position of these two species. The
      cytological analyses of other related clonal cultures suggest an evolutionary
      transition from S. pectinatus towards S. regularis through S. pectinatus f.
      regularis, which correlates with the morphological data about their variability.
      These results are discussed from the cytogenetic, morphological and evolutionary
      point of view. On the basis of the karyotypic analysis, it was confirmed that
      from a taxonomic point of view S. pectinatus, S. acuminatus and S. regularis are
      separate biological species.

PMID- 16809839
TI  - Genetic analyses of agronomic and seed quality traits of synthetic oilseed
      Brassica napus produced from interspecific hybridization of B. campestris and B.
      oleracea.
AB  - The heritability, the number of segregating genes and the type of gene
      interaction of nine agronomic traits were analysed based on F2 populations of
      synthetic oilseed Brassica napus produced from interspecific hybridization of B.
      campestris and B. oleracea through ovary culture. The nine traits-plant height,
      stem width, number of branches, length of main raceme, number of pods per plant,
      number of seeds per pod, length of pod, seed weight per plant and 1000-seed
      weight-had heritabilities of 0.927, 0.215, 0.172, 0.381, 0.360, 0.972, 0.952,
      0.516 and 0.987 respectively, while the mean numbers of controlling genes for
      these characters were 7.4, 10.4, 9.9, 12.9, 11.5, 21.7, 20.5, 19.8 and 6.4
      respectively. According to estimated coefficients of skewness and kurtosis of the
      traits tested, no significant gene interaction was found for plant height, stem
      width, number of branches, length of main raceme, number of seeds per pod and
      1000-seed weight. Seed yield per plant is an important target for oilseed
      production. In partial correlation analysis, number of pods per plant, number of
      seeds per pod and 1000-seed weight were positively correlated with seed yield per
      plant. On the other hand, length of pod was negatively correlated (r = -0.69)
      with seed yield per plant. Other agronomic characters had no significant
      correlation to seed yield per plant. In this experiment, the linear regressions
      of seed yield per plant and other agronomic traits were also analysed. The linear
      regression equation was y = 0.074x8 + 1.819x9 + 6.72x12- 60.78 (R2= 0.993), where
      x8, x9 and x12 represent number of pods per plant, number of seeds per pod and
      1000-seed weight respectively. The experiment also showed that erucic acid and
      oil contents of seeds from F2 plants were lower than those of their maternal
      parents. However, glucosinolate content was higher than that of the maternal
      plants. As for protein content, similar results were found in the F2 plants and
      their maternal parents. It was shown that the four quality traits, i.e. erucic
      acid, glucosinolate, oil content, and protein content, had heritability values of
      0.614, 0.405, 0.153 and 0.680 respectively.

PMID- 16809840
TI  - Microenvironmental variation in preassay rearing conditions can lead to anomalies
      in the measurement of life-history traits.

PMID- 16809841
TI  - Molecular cloning and characterization of a novel human testis-specific gene by
      use of digital differential display.

PMID- 16809842
TI  - An assessment of the genetic diversity and structure within and among populations
      of wild pigs (Sus scrofa) from Australia and Papua New Guinea.

PMID- 16809843
TI  - Microsatellites for the gynogenetic Amazon molly, Poecilia formosa: useful tools
      for detection of mutation rate, ploidy determination and overall genetic
      diversity.

PMID- 16809844
TI  - A clinical and molecular-genetic analysis of Chinese patients with lattice
      corneal dystrophy and novel Thr538Pro mutation in the TGFBI (BIGH3) gene.

PMID- 16809845
TI  - Mutants of Aspergillus nidulans affected in asexual development.

PMID- 16809846
TI  - Chromosome number and meiotic behaviour in Brachiaria jubata (Gramineae).

PMID- 16809847
TI  - Simple laboratory tests of ecological theories: what we can learn from them, and
      when we should be cautious.

PMID- 16809848
TI  - Limbs: gains and losses.

PMID- 16809849
TI  - Hypoxia,hyperoxia and breathing.

PMID- 16809850
TI  - The extent of Charles Darwin's knowledge of Mendel.

PMID- 16809851
TI  - Kenneth Raper, Elisha Mitchell and Dictyostelium.

PMID- 16809852
TI  - Living in a physical world VII. Gravity and life on the ground.

PMID- 16809853
TI  - What history tells us V. Emile Duclaux (1840-1904).

PMID- 16809854
TI  - Interactions of carbohydrates and proteins by fluorophore-assisted carbohydrate
      electrophoresis.
AB  - A sensitive,specific, and rapid method for the detection of carbohydrate-protein
      interactions is demonstrated by fluorophore-assisted carbohydrate electrophoresis
      (FACE). The procedure is simple and the cost is low. The advantage of this method
      is that carbohydrate-protein interactions can be easily displayed by FACE, and
      the carbohydrates do not need to be purified.

PMID- 16809855
TI  - Pleurotus sajor-caju HSP100 complements a thermotolerance defect in hsp104 mutant
      Saccharomyces cerevisiae.
AB  - A putative Hsp100 gene was cloned from the fungus Pleurotus sajor-caju. mRNA
      expression studies demonstrated that this gene (designated PsHsp100) is highly
      induced by high temperature,induced less strongly by exposure to ethanol, and not
      induced by drought or salinity. Heat shock induction is detectable at 37 degrees
      C and reaches a maximum level at 42 degrees C. PsHsp100 mRNA levels sharply
      increased within 15 min of exposure to high temperature, and reached a maximum
      expression level at 2 h that was maintained for several hours. These results
      indicate that PsHsp100 could work at an early step in thermotolerance. To examine
      its function, PsHsp100 was transformed into a temperature-sensitive hsp104
      deletion mutant Saccharomycetes cerivisiae strain to test the hypothesis that
      PsHSP100 is an protein that functions in thermotolerance. Overexpression of
      PsHSP100 complemented the thermotolerance defect of the hsp104 mutant yeast,
      allowing them being survive even at 50 degree C for 4 h. These results indicate
      that PsHSP100 protein is functional as an HSP100 in yeast and could play and
      important role in thermotolerance in P. sajor-caju.

PMID- 16809856
TI  - Genetic transformation of peanut (Arachis hypogaea L.) using cotyledonary node as
      explant and a promoterless gus::nptII fusion gene based vector.
AB  - We have generated putative promoter tagged transgenic lines in Arachis hypogaea
      cv JL-24 using cotyledonary node (CN) as an explant and a promoterless gus::nptII
      bifunctional fusion gene mediated by Agrobacterium transformation. MS medium
      fortified with 6-benzylaminopurine (BAP) at 4mg/l in combination with 0.1 mg/l
      alpha -napthaleneacetic acid (NAA) was the most effective out of the various BAP
      and NAA combinations tested in multiple shoot bud formation. Parameters enhancing
      genetic transformation viz. seedling age, Agrobacterium genetic background and co
      cultivation periods were studied by using the binary vector p35SGUSINT. Genetic
      transformation with CN explants from 6-day-old seedlings co-cultivated with
      Agrobacterium GV2260 strain for 3 days resulted in high kanamycin resistant shoot
      induction percentage (45%); approximately 31% transformation frequency was
      achieved with p35S GUSINT in beta-glucuronidase (GUS) assays. Among the in vivo
      GUS fusions studied with promoterless gus::nptII construct, GUS-positive sectors
      occupied 38% of the total transient GUS percentage. We have generated over 141
      putative T 0 plants by using the promoterless construct and transferred them to
      the field. Among these, 82 plants survived well in the green house and 5 plants
      corresponding to 3.54% showed stable integration of the fusion gene as evidenced
      by GUS, polymerase chain reaction (PCR) and Southern blot analyses. Twenty-four
      plants were positive for GUS showing either tissue-specific expression or blue
      spots in at least one plant part. The progeny of 15 T 0 plants indicated
      Mendelian inheritance pattern of segregation for single-copy integration. The
      tissue-specific GUS expression patterns were more or less similar in both T 0 and
      corresponding T 1 progeny plants. We present the differential patterns of GUS
      expression identified in the putative promoter-tagged transgenic lines in the
      present communication.

PMID- 16809857
TI  - The analysis of proteome changes in sunflower seeds induced by N+ implantation.
AB  - In this work, the proteomic changes induced by N+ ion implantation were
      investigated using a sunflower seed model by a two-dimensional electrophoretic
      analysis. To further understand the changes of total protein irradiated with N+
      ion, a proteomic analysis of N+ ion implantation seeds was developed. Among
      approximately 369 total protein spots displayed in 2-D gels, eight specific
      proteins were found in non-implanted seeds while four proteins were found in
      implanted seeds. Six proteins were used for MALDI-TOF MS analysis, of which only
      two had been reported before. The proteins designated as No.29 showed 23.4%
      homology to MADS-box transcriptional factor HAM59, while No. 279 protein had
      23.20% identity to homeobox-leucine zipper protein HAHB-4. The analysis of
      proteome changes induced by N+ implantation could provide a new clue to studying
      mutation mechanism of ion implantation. To our knowledge, this is the first
      report about the analysis of proteome changes induced by N+ implantation in
      sunflower seeds.

PMID- 16809858
TI  - Overexpression of GbERF confers alteration of ethylene-responsive gene expression
      and enhanced resistance to Pseudomonas syringae in transgenic tobacco.
AB  - GbERF belongs to the ERF (ethylene responsive factor) family of transcription
      factors and regulates the GCC-box containing pathogen-related (PR) genes in the
      ethylene signal transduction pathway. To study the function of GbERF in the
      process of biotic stress, transgenic tobacco plants expressing GbERF were
      generated. Overexpression of GbERF did not change transgenic plant's phenotype
      and endogenous ethylene level. However, the expression profile of some ethylene
      inducible GCC-box and non-GCC-box containing genes was altered, such as PR1b,
      PR2, PR3, PR4, Osmotin, CHN50, ACC oxidase and ACC synthase genes. These data
      indicate that the cotton GbERF could act as a transcriptional activator or
      repressor to regulate the differential expression of ethylene-inducible genes via
      GCC and non-GCC cis-elements. Moreover, the constitutive expression of GbERF in
      transgenic tobacco enhanced the plant's resistance to Pseudomonas syringae pv
      tabaci infection. In conclusion, GbERF mediates the expression of a wide array of
      PR and ethylene-responsive genes and plays an important role in the plant's
      response to biotic stress.

PMID- 16809859
TI  - Genetically modified cyanobacterium Nostoc muscorum overproducing proline in
      response to salinity and osmotic stresses.
AB  - In the parent Nostoc muscorum an active proline oxidase enzyme is required to
      assimilate exogenous proline as a fixed nitrogen source. Cyanobacterial mutants,
      resistant to growth inhibitory action of proline analogue L-azetidine-2
      carboxylate (Ac-R), were deficient in proline oxidase activity, and were over
      accumulators of proline. Proline over-accumulation, resulting either from
      mutational acquisition of the Ac-R phenotype, or from salinity-induced uptake of
      exogenous proline, confirmed enhanced salinity/osmotic tolerance in the mutant
      strain. The nitrogenase activity and photosynthetic O 2 evolution of the parent
      were sensitive to both salinity as well as osmotic stresses than of Ac-R mutant
      strain. In addition, the mutation to Ac-resistant phenotype showed no alteration
      in salinity inducible potassium transport system in the cyanobacterium.

PMID- 16809860
TI  - Bicarbonate kinetics in Indian males.
AB  - Measurement of rates of in vivo substrate oxidation such as that of glucose,
      fatty acids and amino acids, are based on tracer (14C or 13C) data, and often
      depend on the isotopic content of expired CO2. The recovery of tracer-labelled CO
      2 generated from the oxidation of 13C labelled substrates may not be 100% over
      short term. This can lead to underestimation of oxidation rate of substrates, and
      consequently a correction for the incomplete recovery of tracer has to be applied
      by the determination of the recovery of 13CO2 in the breath during tracer
      bicarbonate infusions. We have studied the recovery of tracer-labelled
      bicarbonate using a bolus administration model, and further characterized
      kinetics of bicarbonate using a three-compartment model, to assess which
      compartmental fluxes changed during the change from a fasted state to fed state.
      Recovery of bicarbonate was lower at 69% and 67% (fasted and fed state) than the
      value of 71% and 74% found during earlier longer term of continuous infusions.
      During feeding, there was a 20-fold increase in the flux of bicarbonate between
      the central compartment and the compartment that was equivalent to the viscera.
      This study shows that the difference between the fasted and fed state recovery of
      tracer bicarbonate similar to that obtained with continuous infusions, and that
      bicarbonate fluxes show large changes between different compartments in the body
      depending on metabolic state.

PMID- 16809861
TI  - Mechanism of recycling of post-termination ribosomal complexes in eubacteria: a
      new role of initiation factor 3.
AB  - Ribosome recycling is a process which dissociates the post-termination complexes
      (post-TC) consisting of mRNA-bound ribosomes harbouring deacylated tRNA(s).
      Ribosome recycling factor (RRF), and elongation factor G (EFG) participate in
      this crucial process to free the ribosomal subunits for a new round of
      translation. We discuss the over-all pathway of ribosome recycling in eubacteria
      with especial reference to the important role of the initiation factor 3 (IF3) in
      this process. Depending on the step(s) at which IF3 function is implicated, three
      models have been proposed. In model 1, RRF and EFG dissociate the post-TCs into
      the 50S and 30S subunits, mRNA and tRNA(s). In this model, IF3, which binds to
      the 30S subunit, merely keeps the dissociated subunits apart by its anti
      association activity. In model 2, RRF and EFG separate the 50S subunit from the
      post-TC. IF3 then dissociates the remaining complex of mRNA, tRNA and the 30S
      subunit, and keeps the ribosomal subunits apart from each other. However, in
      model 3, both the genetic and biochemical evidence support a more active role for
      IF3 even at the step of dissociation of the post-TC by RRF and EFG into the 50S
      and 30S subunits.

PMID- 16809862
TI  - Demons, nature, or God? Witchcraft accusations and the French disease in early
      modern Venice.
AB  - In early modern Venice, establishing the cause of a disease was critical to
      determining the appropriate cure: natural remedies for natural illnesses,
      spiritual solutions for supernatural or demonic ones. One common ailment was the
      French disease (syphilis), widely distributed throughout Venice's neighborhoods
      and social hierarchy, and evenly distributed between men and women. The disease
      was widely regarded as curable by the mid-sixteenth century, and cases that did
      not respond to natural remedies presented problems of interpretation to
      physicians and laypeople. Witchcraft was one possible explanation; using expert
      testimony from physicians, however, the Holy Office ruled out witchcraft as a
      cause of incurable cases and reinforced perceptions that the disease was of
      natural origin. Incurable cases were explained as the result of immoral behavior,
      thereby reinforcing the associated stigma. This article uses archival material
      from Venice's Inquisition records from 1580 to 1650, as well as mortality data.

PMID- 16809863
TI  - Imagining inoculation: Smallpox, the body, and social relations of healing in the
      eighteenth century.
AB  - People in colonial New York adopted inoculation for smallpox as quickly and as
      thoroughly as did people anywhere in the British Atlantic world. Such adoption
      was not dependent upon the authority of formal medicine, but rather upon everyday
      epistemology. Inoculation became accepted as local knowledge because ordinary New
      Yorkers integrated it imaginatively into common ideas about the body and disease,
      reconceptualized its theological meaning, and incorporated it into familiar
      social relations of healing.

PMID- 16809864
TI  - A stranger to our camps: Typhus in American history.
AB  - Medical observers during the American Civil War were happily surprised to find
      that typhus fever rarely made an appearance, and was not a major killer in the
      prisoner-of-war camps where the crowded, filthy, and malnourished populations
      appeared to offer an ideal breeding ground for the disease. Through a review of
      apparent typhus outbreaks in America north of the Mexican border, this article
      argues that typhus fever rarely if ever extended to the established populations
      of the United States, even when imported on immigrant ships into densely
      populated and unsanitary slums. It suggests that something in the American
      environment was inhospitable to the extensive spread of the disease, most likely
      an unrecognized difference in the North American louse population compared to
      that of Europe.

PMID- 16809865
TI  - Eugenics, medical education, and the Public Health Service: Another perspective
      on the Tuskegee syphilis experiment.
AB  - The Public Health Service (PHS) Study of Untreated Syphilis in the Male Negro
      (1932-72) is the most infamous American example of medical research abuse.
      Commentary on the study has often focused on the reasons for its initiation and
      for its long duration. Racism, bureaucratic inertia, and the personal motivations
      of study personnel have been suggested as possible explanations. We develop
      another explanation by examining the educational and professional linkages shared
      by three key physicians who launched and directed the study. PHS surgeon general
      Hugh Cumming initiated Tuskegee, and assistant surgeons general Taliaferro Clark
      and Raymond A. Vonderlehr presided over the study during its first decade. All
      three had graduated from the medical school at the University of Virginia, a
      center of eugenics teaching, where students were trained to think about race as a
      key factor in both the etiology and the natural history of syphilis. Along with
      other senior officers in the PHS, they were publicly aligned with the eugenics
      movement. Tuskegee provided a vehicle for testing a eugenic hypothesis: that
      racial groups were differentially susceptible to infectious diseases.

PMID- 16809866
TI  - "A private little revolution": the home pregnancy test in American culture.
AB  - The home pregnancy test went from novelty to norm in twenty-five years. This
      article explores its cultural impact in the context of the women's health
      movement. Though women had long made do without it, the "private little
      revolution," as the test was called in an early advertisement, enabled them to
      take control of their reproductive health care and moved the moment of discovery
      from the doctor's office (back) to the home. The article introduces the test,
      explores its acceptance by physicians and by women, looks at the marketing of the
      test by drug companies, and traces its use in movies, television, and novels.

PMID- 16809870
TI  - Addressing racial and ethnic disparities: lessons from the REACH 2010
      communities.

PMID- 16809871
TI  - REACH 2010: working together to achieve the goal of eliminating health
      disparities.

PMID- 16809872
TI  - The role of faith-based institutions in addressing health disparities: a case
      study of an initiative in the southwest Bronx.
AB  - Although many public health initiatives have been implemented through
      collaborations with faith-based institutions, little is known about best
      practices for developing such programs. Using a community-based participatory
      approach, this case study examines the implementation of an initiative in the
      Bronx, New York, that is designed to educate community members about health
      promotion and disease management and to mobilize church members to seek equal
      access to health care services. The study used qualitative methods, including the
      collaborative development of a logic model for the initiative, focus groups,
      interviews, analysis of program reports, and participant observation. The paper
      examines three key aspects of the initiative's implementation: (1) the engagement
      of the church leadership; (2) the use of church structures as venues for
      education and intervention; and (3) changes in church policies. Key findings
      include the importance of pre-existing relationships within the community and the
      prominent agenda-setting role played by key pastors, and the strength of the
      Coalition's dual focus on health behaviors and health disparities. Given the
      churches' demonstrated ability to pull people together, to motivate and to
      inspire, there is great potential for faith-based interventions, and models
      developed through such interventions, to address health disparities.

PMID- 16809873
TI  - Sustaining a safety net breast and cervical cancer detection program.
AB  - For the past six years, the Chicago-area faith-based Reach Out Consortium has
      mobilized low-income uninsured and underinsured African American women and
      Latinas to seek screening for breast and cervical cancer. The funding history for
      this program illustrates how funds for a small community-based program were
      leveraged into a broader program, and that grew to serve low-income women across
      the state. Further, as the program reached more and more uninsured women,
      community activism led to a further state investment in services for the
      uninsured. Program sustainability and expansion depended on a combination of
      public and private competitive grants and grassroots advocacy.

PMID- 16809875
TI  - Addressing disparities through coalition building: Alabama REACH 2010 lessons
      learned.
AB  - Community-based coalitions have become accepted vehicles for addressing complex
      health problems. Few articles have described the challenges and lessons learned
      from such a process. The purpose of this paper is two-fold: 1) to describe the
      processes involved in building and maintaining the REACH 2010 Alabama Breast and
      Cervical Cancer Control Coalition (ABCCCC) and 2) to highlight the lessons
      learned from this venture. Principles from community-based participatory research
      were used 1) to establish and maintain the ABCCCC, 2) to build coalition
      capacity, and 3) to develop breast and cervical cancer interventions. Over 95% of
      our coalition has been maintained over a 7-year period. The ABCCCC received a
      total of 17 breast and cervical cancer mini-grants. Adherence to ground rules
      such as exhibiting respect and trust and practicing open communication helped to
      solidify our partnership. Lessons learned from the ABCCCC can provide others with
      an in-depth exploration of the processes involved in coalition formation and
      maintenance.

PMID- 16809874
TI  - Community-based participatory research increases cervical cancer screening among
      Vietnamese-Americans.
AB  - Using community-based participatory research methods, a community-research
      coalition in Santa Clara County, California (SCC) conducted a quasi-experimental,
      controlled trial to increase Pap test receipt and to build community capacity
      among Vietnamese-American women. From 1999 to 2004, the Coalition planned and
      implemented an Action Plan with six components: multimedia campaign, lay health
      worker outreach, Vietnamese Pap clinic with patient navigation, registry and
      reminder system, continuing medical education for Vietnamese physicians, and
      restoring a Breast and Cervical Cancer Control Program site. Components were
      evaluated individually. Community-wide, cross-sectional telephone surveys of
      Vietnamese women in SCC (intervention community) and Harris County, Texas
      (comparison community) measured overall project impact. Receipt and currency of
      Pap tests increased significantly in the intervention compared with the
      comparison community. Community involvement, system changes, community and
      research capacity building, dissemination of results, and program sustainability
      were also demonstrated. Community-based participatory research is feasible and
      effective in Vietnamese-American communities.

PMID- 16809876
TI  - REACH-Meharry community-campus partnership: developing culturally competent
      health care providers.
AB  - An important national health care effort is elimination of racial and ethnic
      disparities in six specific conditions: infant mortality, cancer screening and
      management, cardiovascular disease, diabetes, human immunodeficiency virus
      infection, and child and adult immunizations. To address this concern, several
      health entities in Nashville, Tennessee responded to a grant initiative from the
      Centers for Disease Control and Prevention to develop a Racial and Ethnic
      Approaches to Community Health (REACH) demonstration project. The resulting award
      is the Nashville REACH 2010 Project, charged to develop sustainable methods to
      reduce and, in time, eliminate racial and ethnic disparities in cardiovascular
      disease and diabetes in the North Nashville community, where mortality rates of
      these diseases are substantially higher than in other parts of the county. As one
      of its many interests, the project included potential health care providers to
      receive and disseminate messages about disease prevention and health education.
      The present paper describes the community-campus partnership between the
      Nashville REACH 2010 project and the post-baccalaureate program of Meharry
      Medical College, a partnership that enfolded Meharry's pre-professional health
      care students into the community-based participatory service research project to
      increase the awareness and sensitivity of future minority health care providers
      to issues in minority and poor, underserved populations and to increase potential
      providers' familiarity with the processes involved in community-based
      participatory research.

PMID- 16809877
TI  - Diabetes-specific emotional distress among African Americans and Hispanics with
      type 2 diabetes.
AB  - This study examines baseline levels and correlates of diabetes-related emotional
      distress among inner-city African Americans and Hispanics with type 2 diabetes.
      The Problem Areas in Diabetes (PAID) scale, which measures diabetes-related
      emotional distress, was administered to 180 African American and Hispanic adults
      participating in the REACH Detroit Partnership. We examined bivariate and
      multivariate associations between emotional distress and biological,
      psychosocial, and quality of health care variables for African Americans and
      Hispanics. Scores were significantly higher among Hispanics than African
      Americans. Demographic factors were stronger predictors of emotional distress for
      Hispanics than for African Americans. Daily hassles, physician support, and
      perceived seriousness and understanding of diabetes were significant for African
      Americans. Understanding the personal, family and community context of living
      with diabetes and conducting interventions that provide support and coping
      strategies for self-management have important implications for reducing health
      disparities among disadvantaged racial and ethnic groups.

PMID- 16809878
TI  - Racial disparity in the diagnosis of obesity among people with diabetes.
AB  - Studies have suggested that many of the estimated 30.5% of all adults, and 54.8%
      of adults with diabetes, who have a body mass index (BMI) of 30 or greater do not
      have a diagnosis of obesity. The records of 265 people with diabetes in the
      Racial and Ethnic Approaches to Community Health (REACH) 2010 Charleston
      community were audited for race, sex, BMI, and a documentation of obesity, to
      determine the likelihood of a diagnosis of obesity for people with BMI of 30 or
      greater, based on race and sex. Significant differences in diagnosis were
      observed by race, with three times as many records of obese White people with
      diabetes containing a diagnosis of obesity as of diabetic African Americans.
      Disparities in prevalence of obesity based on a BMI of 30 or greater were
      observed as well, with a higher proportion of African Americans meeting the
      criteria. Studies suggest that these disparities may contribute to the increased
      burden of disease experienced by African Americans with diabetes.

PMID- 16809879
TI  - The Association between self-reported discrimination, physical health and blood
      pressure: findings from African Americans, Black immigrants, and Latino
      immigrants in New Hampshire.
AB  - The relationship between perceived racial discrimination and both blood pressure
      and perceived physical health has been documented among African Americans.
      However, this association has not been well-studied for Black or Latino
      immigrants. We used multiple regression analysis with a cross-sectional sample of
      666 African Americans, Black immigrants, and Latino immigrants from the New
      Hampshire Racial and Ethnic Approaches to Community Health 2010 Initiative to
      assess the relationship between discrimination and measures of physical health
      and blood pressure. The study found evidence of a significant U-shaped
      relationship between discrimination and systolic blood pressure for all three
      cohorts. Evidence was also found supporting a negative linear relationship
      between discrimination and physical health. In addition, the association between
      discrimination and physical health was attenuated for Latinos compared with the
      other groups. Future research should evaluate how factors associated with
      acculturation or cumulative exposure to discriminatory stressors may affect the
      protective resources of immigrants.

PMID- 16809880
TI  - Self-reported health among Cambodians in Lowell, Massachusetts.
AB  - National health data reported for Asians in the aggregate present a picture of
      good health, but significant health disparities exist between Southeast Asian
      refugees, and Cambodians in particular, and the overall population of the U.S. To
      effectively address health disparities, ethnically specific data is needed. Data
      from a community survey of 381 Cambodian adults 25 years of age and older are
      presented. Overall, 44% of respondents reported fair or poor health. Using
      multivariate logistic regression, we examined the relationships between self
      rated health and demographics, timing of immigration, language use and literacy,
      and access to health care. In our final model those most likely to report fair or
      poor health were female, older, unable to work due to disability, to have spent a
      smaller proportion of their life in the U.S., and to have wanted to see a doctor
      in the past year, but not been able to.

PMID- 16809881
TI  - Assessing resource environments to target prevention interventions in community
      chronic disease control.
AB  - The recent emphasis in public health and medicine on the environmental
      determinants of chronic illness has created the need for a more comprehensive way
      to assess barriers and facilitators of healthy living. This paper reports on the
      approach taken by a Centers for Disease Control and Prevention (CDC)-funded
      project whose goal is to reduce disparities in diabetes and cardiovascular
      disease in Los Angeles' African American communities. Findings from this
      community-based participatory research project suggest that while location is an
      important variable in evaluating nutritional and physical activity resources,
      quality and price considerations are at least as useful. We argue that every
      community or neighborhood is located within a resource environment for medical
      care, recreation, food, and other health-promoting or health-compromising goods
      and services that affect the lives and health of its residents.

PMID- 16809882
TI  - HIV risk reduction among young minority adults in Broward County.
AB  - We examined changes in perceptions of HIV risk, abstinence, condom use, and
      intentions to use condoms for disease protection among African American,
      Hispanic, Haitian, and Afro-Caribbean unmarried and married men and women living
      in Broward County, Florida. Data were collected through computer-assisted
      telephone interview surveys conducted during 2001, 2002, and 2003 with cross
      sectional probability samples of 18-39 year old residents of 12 high AIDS
      incidence ZIP code areas. Perceptions of HIV risk increased over time for men,
      but not for women. Unmarried Haitian women 18-22 years old were most likely to
      report abstinence. Condom use during the last 12 months increased among sexually
      active respondents. Among residents reporting exposure to project interventions,
      condom use increased from 53.6% in 2001 to 64.7% in 2002 and 71.6% in 2003. HIV
      prevention programs should (1) consider locally collected data; (2) take into
      account cultural, living situation, and other significant differences; and (3) be
      evaluated to assess differentiated impact.

PMID- 16809883
TI  - The emerging role of arsenic trioxide as an immunomodulatory agent in the
      management of multiple myeloma.
AB  - Multiple myeloma is a clonal disorder of plasma cells which is considered
      incurable with currently available therapies. Substantial advances have been
      achieved in the past decade with the identification of cellular mechanisms that
      confer drug resistance. This has resulted in newer agents such as arsenic
      trioxide (Trisenoxt), lenalidomide (Revlimid) and bortezomib (Velcade) with
      promising activity in this disease. In this review article we will outline the
      history, mechanisms of action, pharmacology, and clinical trials of arsenic
      trioxide in multiple myeloma.

PMID- 16809884
TI  - Effect of imatinib mesylate combined with granulocyte colony-stimulating factor
      on leukaemic blast cells derived from advanced-stage chronic myelogenous
      leukaemia patients.
AB  - Neutropenia is a severe adverse effect that can occur when treating patients with
      imatinib mesylate for advanced-stage chronic myelogenous leukaemia (CML).
      Therefore, we evaluated in vitro the combined effect of imatinib and granulocyte
      colony-stimulating factor (G-CSF) on proliferation and apoptosis of Bcr-Abl
      expressing leukaemic cells to infer the safety of G-CSF administration. In KU812
      and K562 cell lines, G-CSF neither stimulated their proliferation nor abolished
      the suppressive effect of imatinib. However, it stimulated the proliferation of
      blast cells in 2 out of the 5 cases with advanced-stage CML. These in vitro
      studies appear to provide data for the decision of G-CSF administration in
      combination with imatinib in the treatment of neutropenic patients with advanced
      stage CML.

PMID- 16809885
TI  - Platelet activation in Helicobacter pylori-associated idiopathic thrombocytopenic
      purpura: eradication reduces platelet activation but seldom improves platelet
      counts.
AB  - INTRODUCTION: It has been suggested that Helicobacter pylori eradication often
      increases platelet counts in patients with chronic idiopathic thrombocytopenic
      purpura (ITP). In addition, H. pylori has been shown to induce platelet
      activation (CD62p or P-selectin expression) in previous studies. We assessed the
      response of platelet count and CD62p expression after eradication therapy in
      patients with ITP and H. pylori infection. METHODS AND RESULTS: We prospectively
      studied 15 ITP patients diagnosed with H. pylori infection by serology and breath
      test. A follow-up breath test was used to document eradication. Two out of 15
      patients showed improvement in platelet counts after 6 months, 1 of which may
      have had drug-induced thrombocytopenia. Overall, certain platelet response rate
      in our series was 6.7% (1/15). We found that platelet CD62p expression by flow
      cytometry was elevated in 10/15 (66.7%) H. pylori-infected patients, which is a
      statistically significant difference when compared with 3/33 (9.1%) control ITP
      patients seronegative for H. pylori (p = 0.002). In addition, eradication therapy
      decreased CD62p expression (p = 0.04). However, reduction in platelet activation
      was not associated with an increase in platelet counts (mean 72.4 x 10(9)/l
      before and 68.7 after therapy; p = 0.4). CONCLUSION: In our series, platelet
      activation was common in ITP patients with H. pylori, and eradication therapy
      decreased platelet activation but seldom increased platelet counts. Increased
      platelet CD62p expression is a putative link between chronic infections and
      atherosclerosis, but further study is needed to clarify the implications of our
      observation.

PMID- 16809886
TI  - Lung function in beta-thalassemia patients: a longitudinal study.
AB  - Patients with beta-thalassemia often present with a restrictive pattern at
      pulmonary function tests (PFTs) due to several pathogenetic factors. However, the
      long-term evolution is unknown. We performed a longitudinal study of pulmonary
      function in asymptomatic, non-smoking patients with beta-thalassemia major and
      intermedia. We looked for temporal changes in lung function and characteristics
      that would predict the development of PFT abnormalities. In 1996, 18 patients
      with major beta-thalassemia (9 males and 9 females; age range: 18-35 years) and
      11 patients with intermediate beta-thalassemia (5 males and 6 females; age range:
      25-51 years) underwent clinical assessment and PFT, including body
      plethysmography and gas transfer study (carbon monoxide diffusion capacity,
      DL(CO)). Patients were reassessed in 2003. An echocardiographic evaluation was
      also obtained to exclude pulmonary hypertension. In 55.5% of major and 45.4% of
      intermediate beta-thalassemia patients, a restrictive pattern was found in 1996;
      in 2003 only 38.8 and 27.2% of patients, respectively, exhibited total lung
      capacities below the predicted values. DL(CO) was unchanged in both groups of
      patients, being reduced in 5 thalassemia major patients and within the normal
      range in intermediate patients. We conclude that asymptomatic patients with beta
      thalassemia have a high prevalence of PFT abnormalities, but without significant
      increases over time. An improvement may be observed when good control of the iron
      balance is reached with optimal chelation therapy.

PMID- 16809888
TI  - Fetal haematocrit is a determinant of placental size in term pregnancies.
AB  - Placental size may be influenced by maternal factors, placental function as well
      as the fetal condition. So far, no studies have examined how the fetal oxygen
      carrying capacity or haemoglobin/haematocrit levels would affect placental growth
      in normal human pregnancies. The aim of this study was to investigate the
      relationships between placental size and fetal arterial cord blood haemoglobin
      and haematocrit levels at the time of caesarean delivery. Umbilical arterial cord
      blood was taken for arterial haemoglobin and haematocrit levels immediately after
      delivery. The relative placental size (defined by the ratio of placental weight
      to fetal weight) was inversely correlated with both arterial haemoglobin (r = 
      0.455, p = 0.001) and haematocrit levels (r = -0.425, p = 0.003) in women who had
      undergone elective caesarean sections. No significant correlation was found
      between the relative placental size with other maternal and fetal factors.

PMID- 16809887
TI  - Troglitazone inhibits cell growth and induces apoptosis of B-cell acute
      lymphoblastic leukemia cells with t(14;18).
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the
      nuclear receptor superfamily, has been detected in several human leukemia cells.
      Recent studies reported that PPARgamma ligands inhibit cell proliferation and
      induce apoptosis in both normal and malignant B-lineage cells. We investigated
      the expression of PPARgamma and the effects of PPARgamma ligands on UTree-O2,
      Bay91 and 380, three B-cell acute lymphoblastic leukemia (B-ALL) cell lines with
      t(14;18), which show a poor prognosis, accompanying c-myc abnormality. Western
      blot analysis identified expression of PPARgamma protein and real-time PCR that
      of PPARgamma mRNA on the three cell lines. Troglitazone (TGZ), a synthetic
      PPARgamma ligand, inhibited cell growth in these cell lines in a dose-dependent
      manner, which was associated with G(1) cell cycle arrest and apoptosis. We also
      found this effect PPARgamma independent since PPARgamma antagonists failed to
      reverse this effect. We assessed the expression of c-myc, an apoptosis-regulatory
      gene, since c-myc abnormality was detected in most B-ALL cells with t(14;18). TGZ
      was found to dose-dependently downregulate the expression of c-myc mRNA and c-myc
      protein in the three cell lines. These results suggest that TGZ inhibits cell
      growth via induction of G(1) cell cycle arrest and apoptosis in these cell lines
      and that TGZ-induced apoptosis, at least in part, may be related to the
      downregulation of c-myc expression. Moreover, the downregulation of c-myc
      expression by TGZ may depend on a PPARgamma-independent mechanism. Further
      studies indicate that PPARgamma ligands may serve as a therapeutic agent in B-ALL
      with t(14;18).

PMID- 16809889
TI  - Frequency of hypoferritinemia, iron deficiency and iron deficiency anemia in
      outpatients.
AB  - The prevalence rates of hypoferritinemia (IDec/one abnormal indicator), iron
      deficiency (IDef/two abnormal indicators) and iron deficiency anemia (IDA) in
      children who were referred to the outpatient clinics of the Department of
      Pediatrics for the first time within 1 month were investigated. Exclusion
      criteria were iron therapy before and during the study period and a history of
      chronic illness. Acute-phase reactants, such as erythrocyte sedimentation rate
      and C-reactive protein levels, were measured in all cases indicative of
      infectious diseases. Blood samples were obtained from each study patient admitted
      to the outpatient clinics during the study period. The hospital charts were later
      further evaluated, and samples of patients with any current illness known to
      interact with the iron status of the patient were discarded, and patients were
      contacted to supply new samples about 1 month after treatment of the infection.
      Thus, in patients with indications of an infection, samples obtained 1 month
      after treatment were assessed. The children (n = 557) were divided into four age
      groups: those aged 4 months to 2 years (group I), 2-6 years (group II), 7-12
      years (group III) and 12-18 years (group IV). Children with a decrease in serum
      ferritin levels without anemia (IDec), and those with lower ferritin, transferrin
      saturation (TS) and serum iron (SI) concentration (IDef) were evaluated. IDA was
      diagnosed if hemoglobin (Hb) concentrations were lower than those adjusted for
      age, ferritin <12 ng/ml and TS <or=16% and if SI was decreased. IDec, IDef and
      IDA were detected in 26, 11.1 and 12.7% of the patients, respectively. Only 50.1%
      of the patients visiting the outpatient clinics were found to be normal. The
      rates of IDec (28.9%), IDef (21.9%) and IDA (26.2%) were highest in group I. IDec
      had the highest percentages in all groups. In group I, the rates of IDec, IDef,
      and IDA were 37.2, 66.1 and 69%, respectively. SI concentration was abnormal in
      77.1% of the cases in group I (4 months to 2 years of age). Half of the patients
      referred to the outpatient clinics were suffering from abnormalities related to
      lower SI concentrations. Close monitoring and treatment of iron deficiency is
      advised especially in early childhood.

PMID- 16809890
TI  - Treatment of iron deficiency anemia with intravenous iron preparations.
AB  - OBJECTIVE: We aimed to determine the effects of intravenous iron therapy on blood
      parameters in pediatric patients who do not tolerate oral iron therapy for any
      reason. PATIENTS AND METHODS: The patient group consisted of candidates for
      elective operations requiring blood transfusions in order to raise hemoglobin
      (Hb) concentrations rapidly and for whom oral iron administration is useless and
      compliance with long-term treatment is definitely impossible due to sociocultural
      factors. Sixty-two children were included in the study. Venous blood samples were
      taken at diagnosis, and after 1 week and 1, 2 and 3 months. Hb, hematocrit,
      erythrocyte indices (mean erythrocyte volume, mean erythrocyte Hb and mean
      erythrocyte Hb concentration), serum iron (SI) levels, iron binding capacity,
      transferrin receptor (CD71) and serum ferritin levels were measured. Iron sucrose
      was used as an intravenous iron preparation. RESULTS: All children showed
      improvements in iron deficiency anemia. A statistically significant elevation
      occurred between the time of diagnosis and week 1 (p<0.05) in nearly all
      parameters. SI was raised until at least 1 month of therapy. There was no
      significant difference between transferrin receptors measured before and after
      the intravenous iron therapy. Ferritin did not exceed the values achieved in the
      1st month. Mild side effects were encountered in only 8 (12.9%) patients.
      Treatment was not discontinued because of side effects in any case. The patients
      in the control group were given an oral form containing ferroglycine sulfate.
      CONCLUSION: Intravenous iron therapy can replace oral therapy in patients whose
      blood parameters must be raised rapidly and in situations where oral iron
      administration would not be appropriate for any reason. However, reinforcement
      with oral iron therapy or additional intravenous doses would be appropriate.

PMID- 16809891
TI  - Acute abdomen by varicella zoster virus induced gastritis after autologous
      peripheral blood stem cell transplantation in a patient with non-Hodgkin's
      lymphoma.
AB  - We report on a 54-year-old male patient with an aggressive T cell non-Hodgkin's
      lymphoma with abdominal manifestation undergoing autologous peripheral blood stem
      cell transplantation after high-dose chemotherapy in April 2003. About 4 months
      after transplantation, he developed severe upper abdominal pain. Ultrasound
      examination, X-ray, computed tomography of the abdomen and cardiac diagnostics
      could not explain the symptoms. While empiric therapy with high-dose acyclovir
      was started, we could document herpetic lesions in the gastric antrum by
      endoscopy. The epigastric pain rapidly decreased within several days after the
      start of acyclovir therapy. No herpetic skin lesions were observed at any time
      during the disease. This report demonstrates the importance of viral-induced
      gastritis in the differential diagnosis of severe abdominal pain in patients
      receiving autologous peripheral blood stem cell transplantation.

PMID- 16809892
TI  - True malignant histiocytosis with trisomy 9 following primary mediastinal germ
      cell tumor.
AB  - A 24-year-old Japanese man was admitted due to bloody phlegm in May 2002. A
      diagnosis of mediastinal germ cell tumor, mixed type involving seminoma, immature
      teratoma and embryonal carcinoma, was made by transthoracic needle biopsy. Three
      months later, his complete blood counts revealed pancytopenia with high fever.
      Examination of bone marrow revealed increased atypical large histiocytes (5.6%)
      with hemophagocytosis, and thus, hemophagocytic syndrome related to germ cell
      tumor was diagnosed. In addition, chromosomal analysis of the bone marrow cells
      revealed a 47, XY, +9 genotype. Chemotherapies for germ cell tumor and
      hemophagocytic syndrome were performed without any improvement, and he died of
      diffuse alveolar damage. Autopsy revealed diffuse infiltration of immature
      histiocytes with hemophagocytosis in the liver, spleen and bone marrow. The
      atypical histiocytes were positive for CD68 and lysozyme and negative for
      lymphoid markers, and the diagnosis of true malignant histiocytosis associated
      with mediastinal germ cell tumor was made. The rare chromosomal abnormality of
      trisomy 9, a marker for benzene-related leukemia, was seen in the present case
      without apparent benzene exposure.

PMID- 16809893
TI  - Fulminant stroke in an adult patient with sickle cell anemia.

PMID- 16809894
TI  - Very low doses of thalidomide as single agent in relapsed/refractory multiple
      myeloma.

PMID- 16809895
TI  - Immunoglobulin V(H) genes and CD38 expression analysis in B-cell chronic
      lymphocytic leukemia.

PMID- 16809896
TI  - Diagnostic pitfalls and fallacies of measuring antiplatelet antibodies.

PMID- 16809897
TI  - Non-transferrin-bound iron is associated with enhanced Staphylococcus aureus
      growth in hemodialysis patients receiving intravenous iron sucrose.
AB  - BACKGROUND: Hemodialysis vascular access infections are most frequently caused by
      Staphylococcus spp. The purpose of this study was to determine if S. aureus
      growth is enhanced after administration of IV iron sucrose and to establish a
      relationship between the appearance of non-transferrin-bound iron (NTBI) and S.
      aureus growth. METHODS: Serum samples were obtained from 12 hemodialysis patients
      receiving maintenance doses of 100 mg of iron sucrose at baseline and 5, 30, 90,
      220 min and 48 h after iron administration. Assays for NTBI and transferrin
      saturation were performed. S. aureus isolates were used to inoculate patient
      serum samples. Bacterial growth was determined by optical density. RESULTS: Six
      of 12 patients had NTBI present within 30 min of the iron dose. NTBI was present
      more frequently in patients with baseline transferrin saturation values >30% (p <
      0.05). Bacterial growth was significantly greater in patients who had NTBI
      present at 5, 90 and 220 min after iron administration compared to those who did
      not have NTBI present. CONCLUSIONS: Doses of 100 mg of iron sucrose are
      associated with the presence of NTBI and enhanced S. aureus growth.

PMID- 16809898
TI  - Effect of chronic renal failure on arginase and argininosuccinate synthetase
      expression.
AB  - BACKGROUND: L-arginine (L-arg) participates in numerous biological functions
      including urea and nitric oxide synthesis. Sources of L-arg include dietary
      proteins and endogenous synthesis by argininosuccinate synthetase and
      argininosuccinate lyase. L-arg is converted to urea by arginase I in the liver
      and arginase II in the kidney. Normally, the liver fully consumes L-arg for urea
      generation and does not contribute to its circulating pool. Instead, much of the
      circulating L-arg is produced by the kidney. If true, plasma L-arg should be
      severely reduced in chronic renal failure (CRF); however, plasma L-arg is
      frequently unchanged in CRF. We hypothesized that preservation of plasma L-arg in
      CRF may be, partly, due to downregulation/inhibition of arginase. METHODS:
      Argininosuccinate synthetase, arginase I and II protein abundance and activity
      were measured in the liver and kidneys of rats 6 weeks after 5/6 nephrectomy or
      sham operation. In addition, arginase activity was measured in the presence of
      different urea concentrations to simulate azotemia in vitro. RESULTS: Arginases I
      and II protein abundance as well as arginase activity in the liver, measured in
      the physiological buffer, were similar among the CRF and control groups. However,
      in vitro experiments simulating a uremic milieu revealed a marked concentration
      dependent inhibition of arginase activity by urea in the tissue lysates. CRF had
      no significant effect on argininosuccinate synthetase abundance in the kidney,
      liver, spleen or intestine. CONCLUSIONS: Although CRF does not change the
      abundance or intrinsic properties of arginase, the inherent rise in urea
      concentration inhibits its enzymatic activity. The latter, in turn, attenuates L
      arg catabolism and urea production and, thereby, mitigates the fall in plasma L
      arg.

PMID- 16809899
TI  - Adolescence: a critical period for long-term tracking of risk for coronary heart
      disease?
AB  - Tracking of dietary and physical activity patterns throughout adolescence into
      adulthood is low, which indicates that risk patterns for coronary heart disease
      are not maintained. Biological risk factors for heart disease, particularly
      obesity and clusters of nutritionally modifiable risk factors (e.g. the metabolic
      syndrome), display somewhat higher tracking correlations. Tracking gives little
      guidance as to how to use this information for screening purposes. For behavioral
      and biological risk factors predictive values and sensitivities and specificities
      are generally low, suggesting that population-based approaches are likely to be
      more effective than targeting only the high-risk subset for reducing the risk of
      coronary heart disease.

PMID- 16809900
TI  - Analysis of retinol concentrations in bovine liver and its habitual consumption
      by pregnant women.
AB  - AIMS: The objectives of this study were to analyze retinol concentrations in two
      groups of bovine liver, to estimate the habitual consumption of bovine liver
      among pregnant women, and, based on these data, to evaluate the women's ingestion
      of vitamin A. METHOD: 60 samples of bovine liver, 30 of the Nelore breed and 30
      of undefined breed (UB), were analyzed using the high-performance liquid
      chromatography (HPLC) method for retinol dosage. 100 women under care at the
      University Maternity Hospital Januario Cicco, UFRN, in Natal, RN, Brazil,
      completed the Frequency of Nourishment Questionnaire. RESULTS: The mean +/- SD
      values for the retinol concentrations in the liver samples of the Nelore breed
      and the UB groups were 16,947.8 +/- 6,866.9 and 5,213.1 +/- 2,517.2 microg of
      retinol/100 g, respectively. A high number of women consumed liver (73%) and in
      71% of the cases the advice for the consumption of this food was provided by
      qualified professionals. CONCLUSION: It is concluded that the daily consumption
      of the bovine liver is not recommended for pregnant women, regardless of the
      genetic origin of the animal. The study alert health professionals of the danger
      of recommending the ingestion of bovine liver during pregnancy.

PMID- 16809901
TI  - Differences in measured and self-reported height and weight in Dutch adolescents.
AB  - BACKGROUND/AIMS: Monitoring overweight prevalence and its trends in Dutch youth
      is frequently based on self-reported data. The validity of self-reported data
      especially in young adolescents is not sufficiently known. The purpose of this
      study is to study the validity of self-reported height and weight in 12- to 13
      year-olds, to identify sociodemographic correlates and to explore whether
      correction factors can be developed to estimate the prevalence of overweight in
      youth. METHODS: 5,525 12- to 13-year-old pupils in the Rotterdam area filled in a
      confidential questionnaire on health topics, including their height and weight.
      In a sub-sample of 499 pupils both self-reported and measured height and weight
      were available. RESULTS: Self-reported data led to a considerable underestimation
      of Body Mass Index and consequently the prevalence of overweight. Underestimation
      was higher in pupils who regarded themselves as more fat, were of non-Dutch
      origin and in lower education levels. CONCLUSION: Self-reported height and weight
      appeared to be inappropriate to estimate the overweight prevalence in 12- to 13
      year-olds, unless the figures were adjusted. Using adjusted self-reported BMI on
      an individual level is questionable. Actual measurements of height and weight are
      necessary to draw up valid correction formulas in new samples.

PMID- 16809902
TI  - The effects of a mixture of brown and black rice on lipid profiles and
      antioxidant status in rats.
AB  - BACKGROUND: The present study was designed to investigate the influence of
      natural brown and black rice consumption on serum lipid parameters and hepatic
      enzyme activities in rats fed different combinations of grains. METHODS: 50 male
      rats were divided into 4 groups and raised for 8 weeks on diets containing white
      rice (WH), white rice and brown rice (WHBR), white rice and black rice (WHBL),
      brown rice and black rice (BRBL). Blood samples were collected for lipid
      measurements, and the oxidant and antioxidant status of liver was evaluated.
      RESULTS: Plasma triglyceride, total cholesterol and low-density lipoprotein
      cholesterol in rats fed the WH diet were higher than in other groups. High
      density lipoprotein cholesterol was significantly higher in rats fed diets
      including black rice such as WHBL and BRBL compared with WH and WHBR. The level
      of thiobarbituric acid reactive substances in liver is shown to be higher in rats
      in the order of those fed WH, WHBR, WHBL and BRBL. While superoxide dismutase and
      chloramphenicol acetyltransferase did not differ among the 4 groups, glutathione
      and glutathione peroxidase in WH were significantly lower than in other groups.
      CONCLUSION: This study demonstrates that brown and black rice have
      cardioprotective effects.

PMID- 16809903
TI  - Influence of ALA54THR polymorphism of fatty acid binding protein 2 on lifestyle
      modification response in obese subjects.
AB  - BACKGROUND/AIM: It has been found that the expression of fatty acid binding
      protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54
      of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This
      polymorphism was associated with high insulin resistance and high fasting insulin
      concentrations. The aim of our study was to investigate the influence of Thr54
      polymorphism in the FABP2 protein on the response to a lifestyle modification
      (Mediterranean hypocaloric diet and exercise) in obese patients. METHODS: A
      population of 69 obese (body mass index > 30) nondiabetic outpatients was
      analyzed in a prospective way. Before and after 3 months of the lifestyle
      modification program, indirect calorimetry, tetrapolar electrical bioimpedance
      measurement, blood pressure recording, serial assessment of the nutritional
      intake (3 days of written food records), and biochemical analysis were performed.
      The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal;
      52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted
      of aerobic exercise for at least three times/week (60 min each). Statistical
      analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group
      and wild-type Ala54/Ala54 as second group. RESULTS: The mean age was 45.5 +/-
      16.7 years, the mean body mass index was 34.1 +/- 5.1, and there were 14 males
      (20.3%) and 55 females (79.7%) with a weight loss of 3.17 +/- 3.5 kg (3.5%).
      Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and
      32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the
      genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight
      loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body
      mass index, weight, fat mass, low-density lipoprotein cholesterol level, and
      waist circumference decreased, whereas the VO2 (oxygen consumption) increased. In
      the mutant group, glucose, body mass index, weight, waist circumference, and
      systolic blood pressure decreased, and VO2 increased. No differences were
      detected between basal values in both groups. Only the leptin levels showed a
      significant decrease in the wild-type group (23.85%; p < 0.05), with no
      statistically significant difference in the mutant group (2.59%; NS). Resistin,
      tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein
      remained without changes in both groups. CONCLUSIONS: Weight loss is associated
      with different changes, depending on the FABP2 genotype. Carriers of the Thr54
      allele have a different response than wild-type obese subjects, with a
      significant decrease of systolic blood pressure and glucose levels in Thr54
      carriers and a significant decrease in fat mass, low-density lipoprotein
      cholesterol, and leptin in wild-type patients.

PMID- 16809904
TI  - Aspects of protein and amino acid metabolism in a model of severe glutamine
      deficiency in sepsis.
AB  - BACKGROUND/AIMS: Growth hormone (GH) could have the potential to improve protein
      metabolism in sepsis but glutamine deficiency has been reported after GH
      treatment. The aim was to investigate the effects of glutamine deficiency in
      sepsis with and without GH treatment on protein and amino acid metabolism.
      METHODS: Cecal ligation and puncture (CLP) was used as a model of sepsis. Serious
      glutamine deficiency was induced by administration of glutamine synthetase
      inhibitor, methionine sulfoximine (MSO). Young Wistar rats were divided into 5
      groups: control; CLP; CLP+MSO; CLP+GH, and CLP+MSO+GH. Parameters of protein
      metabolism were measured on incubated soleus and extensor digitorum longus
      muscles: [1-14C]leucine was used to estimate protein synthesis and leucine
      oxidation, tyrosine release was used to evaluate protein breakdown. Amino acid
      concentrations in plasma, skeletal muscle and incubation media were measured by
      HPLC. RESULTS/CONCLUSIONS: A reduced muscle glutamine concentration after MSO
      treatment is not associated with changes in the rates of protein synthesis or
      breakdown. MSO treatment decreased glutamine release from skeletal muscle and
      plasma glutamine concentration. Severe glutamine deficiency in GH-treated septic
      rats resulted in increased release of branched-chain amino acids from skeletal
      muscle.

PMID- 16809905
TI  - Methemoglobinemia caused by the ingestion of courgette soup given in order to
      resolve constipation in two formula-fed infants.
AB  - Methemoglobinemia is not a rare condition arising from the exposure to hemoglobin
      oxidizing agents such as nitrates-nitrites present in well water or vegetables.
      Infants < 3 months of age are more susceptible than adults because of lower
      amounts of a key enzyme, NADH-cytochrome b5 reductase, which converts
      methemoglobin back to hemoglobin. We report 2 infants, aged respectively 2 and 1
      months, suffering from methemoglobinemia, fed with a formula that was
      reconstituted with a high concentration of courgette soup to resolve
      constipation. They developed a severe cyanosis with methemoglobinemia
      (respectively 30.4 and 27%) and were hospitalized and treated with methylene blue
      at 1%. After 12 h the syndrome was completely resolved. Home-prepared infant
      foods containing vegetables are potential causes of methemoglobinemia. It is
      important not to feed infants with vegetables having a high nitrate content
      (e.g., courgette, spinach, beets and green beans) to resolve constipation since,
      particularly in the first months of life, they may cause severe
      methemoglobinemia.

PMID- 16809906
TI  - Serum retinol, alpha-tocopherol, and beta-carotene levels are not altered by
      excess ingestion of diacylglycerol-containing plant sterol esters.
AB  - BACKGROUND: Diacylglycerol (DAG) suppresses the postprandial increase in serum
      triglycerides, and has antiobesity effects. On the other hand, plant sterol
      esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG
      containing PSE (PSE/DAG) would be expected to maintain an appropriate serum
      cholesterol level and decrease the risk of arteriosclerotic disorders. Several
      recent studies, however, report negative effects of PSE on serum fat-soluble
      (pro)vitamin levels. The objective of this study was to investigate the effect of
      PSE/DAG on serum retinol, beta-carotene, and alpha-tocopherol levels using a
      threefold excess of the effective dose obtained in our previous study. METHODS: A
      randomized placebo-controlled double-blind parallel study was performed in
      healthy and mildly hypercholesterolemic subjects, in which the subjects ingested
      1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products.
      Triacylglycerol (TAG) mayonnaise was used as a control. RESULT: There were no
      subjective adverse effects or changes in serum retinol, alpha-tocopherol, and
      beta-carotene levels, abdominal symptoms, hematologic values, or blood
      biochemical values. CONCLUSION: Ingestion of a threefold excess of PSE/DAG for 2
      weeks had no adverse effects compared to ingestion of conventional TAG
      mayonnaise.

PMID- 16809907
TI  - Oral administration of hot water extracts of Chlorella vulgaris increases
      physical stamina in mice.
AB  - BACKGROUND/AIMS: A unicellular algae, Chlorella vulgaris, was used as a
      biological response modifier. Although hot water extracts of C. vulgaris (CVE)
      are thought to augment immune responses, the effect of CVE on fatigue and
      physical stamina has not been studied. METHODS: In the present study, we
      investigated the effect of CVE on forced swimming test and blood biochemical
      parameters related to fatigue, blood urea nitrogen (BUN), creatine kinase (CK),
      lactic dehydrogenase (LDH), glucose (Glc), and total protein (TP). CVE (0.05-0.15
      g/kg/day) was orally administered to mice. RESULTS: After 7 days, the immobility
      time was decreased in the 0.1- and 0.15-g/kg CVE-treated groups (179 +/- 8.3 and
      175 +/- 2.1 s) in comparison with the control group (223 +/- 5.4 s). In addition,
      the contents of BUN, CK, and LDH in the blood serum were decreased in the CVE-fed
      group. However, they had no effect on the elevation of Glc and TP level.
      CONCLUSIONS: The results predict a potential benefit of CVE for enhancing immune
      function and improving physical stamina.

PMID- 16809908
TI  - The hypothalamic supraoptic and paraventricular nuclei of the echidna and
      platypus.
AB  - The monotremes are an intriguing group of mammals that have major differences in
      their reproductive physiology and lactation from therian mammals. Monotreme young
      hatch from leathery skinned eggs and are nourished by milk secreted onto areolae
      rather than through nipples. Parturition and lactation are in part controlled
      through the paraventricular and supraoptic nuclei of the hypothalamus. We have
      used Nissl staining, enzyme histochemistry, immunohistochemistry for tyrosine
      hydroxylase, calbindin, oxytocin, neurophysin and non-phosphorylated
      neurofilament protein, and carbocyanine dye tracing techniques to examine the
      supraoptic and paraventricular nuclei and the course of the hypothalamo
      neurohypophysial tract in two monotremes: the short-beaked echidna (Tachyglossus
      aculeatus) and the platypus (Ornithorhynchus anatinus). In both monotremes, the
      supraoptic nucleus consisted of loosely packed neurons, mainly in the
      retrochiasmatic position. In the echidna, the paraventricular nucleus was quite
      small, but had similar chemoarchitectural features to therians. In the platypus,
      the paraventricular nucleus was larger and appeared to be part of a stream of
      magnocellular neurons extending from the paraventricular nucleus to the
      retrochiasmatic supraoptic nucleus. Immunohistochemistry for non-phosphorylated
      neurofilament protein and carbocyanine dye tracing suggested that hypothalamo
      neurohypophysial tract neurons in the echidna lie mainly in the retrochiasmatic
      supraoptic and lateral hypothalamic regions, but most neurophysin and oxytocin
      immunoreactive neurons in the echidna were found in the paraventricular, lateral
      hypothalamus and supraoptic nuclei and most oxytocinergic neurons in the platypus
      were distributed in a band from the paraventricular nucleus to the
      retrochiasmatic supraoptic nucleus. The small size of the supraoptic nucleus in
      the two monotremes might reflect functional aspects of monotreme lactation.

PMID- 16809909
TI  - Large brains and lengthened life history periods in Odontocetes.
AB  - Previous work on primates and birds suggests that large brains require longer
      periods of juvenile growth, leading to reproductive constraints due to delayed
      maturation. However, longevity is often extended in large-brained species,
      possibly compensating for delayed maturation. We examined the relationship
      between brain size and life history periods in cetaceans, a large-brained
      mammalian order that has been largely ignored. We looked at males and females of
      twenty-five species of Odontocetes, using independent contrasts and multiple
      regressions to disentangle possible phylogenetic effects and inter-correlations
      among life history traits. We corrected all variables for body size allometry and
      separated life span into adult and juvenile periods. For females and both sexes
      combined, gestation, time to sexual maturity, time as an adult and life span were
      all positively associated with residual brain size in simple regressions; in
      multiple regressions, maximum life span and time as an adult were the best
      predictors of brain size. Males showed few significant trends. Our results
      suggest that brain size has co-evolved with extended life history periods in
      Odontocetes, as it has in primates and birds, and that a lengthened adult period
      could have been an important component of encephalization in cetaceans.

PMID- 16809910
TI  - Can cerebrospinal fluid uric acid levels differentiate intraventricular
      hemorrhage from traumatic tap?
AB  - OBJECTIVE: To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels
      of neonates with intraventricular hemorrhage (IVH), and to examine whether or not
      UA can be used to differentiate traumatic tap from IVH. MATERIAL AND METHODS: The
      control group (n = 19, group I) consisted of neonates presenting with signs
      requiring analysis of CSF but whose CSF indices proved to be normal. Traumatic
      taps (n = 15, group II) were mimicked by adding 2 drops of homologous blood to
      normal CSF samples. The IVH group (n = 21, group III) consisted of neonates who
      had been diagnosed by cranial ultrasonography or computed tomography scans. Data
      are presented as median (range). RESULTS: There was no significant difference
      between groups with respect to serum UA levels. While no significant difference
      was observed between CSF UA levels of the control [0.6 (0.1-1.8) mg/dl] and
      traumatic tap group [0.5 (0.3-1.1) mg/dl], the IVH group [1.6 (0.7-6.9) mg/dl]
      was found to have significantly higher CSF UA levels than groups I and II.
      Furthermore, although there were significant correlations between serum and CSF
      UA levels in the control and traumatic tap groups, no correlation was observed in
      the IVH group. CONCLUSION: CSF UA levels are increased in neonates with IVH and
      they may be used to differentiate a real hemorrhage from a traumatic tap.

PMID- 16809911
TI  - Glucagon-like peptide-1 is involved in sodium and water homeostasis in humans.
AB  - In previous studies with glucagon-like peptide-1 (GLP-1) we have observed that
      this peptide modulates fluid intake and increases renal sodium excretion in
      healthy volunteers and in patients with diabetes mellitus type 2. The effect of
      GLP-1 on thirst, water intake and on osmoregulation has, however, not been
      examined in detail in humans. METHODS: Seventeen healthy male subjects were
      enrolled in two double-blind, placebo-controlled studies. In study part A, 8
      volunteers participated in a protocol with an intravenous salt load of 26.7 +/-
      0.9 g comparing the effect of an infusion of GLP-1 (1.5 pmol/kg x min) to
      isotonic saline (placebo). Sodium excretion and water intake were measured. In
      part B, 9 volunteers were challenged with an oral salt load of 27.7 +/- 0.5 g;
      sodium excretion and water intake were determined comparing an infusion of GLP-1
      (1.5 pmol/kg x min) to isotonic saline (placebo). In part C, intestinal biopsies
      along the gastrointestinal tract were obtained from 14 healthy subjects.
      Expression of human GLP-1 receptor mRNA was measured by real-time polymerase
      chain reaction. RESULTS: In study part A, an increase in renal sodium excretion
      was demonstrated: FeNa rose from 1.6 +/- 0.3 (placebo) to 2.7 +/- 0.2% (GLP-1; p
      = 0.0005). There was no difference in water consumption between the two
      treatments: 1,291 +/- 69 (saline) vs. 1,228 +/- 74 ml (GLP-1; p = 0.49). In part
      B, an oral salt challenge of 27.7 +/- 0.5 g led to an increased renal excretion
      of sodium during GLP-1: FeNa increased from 1.6 +/- 0.2% (placebo) to 2.0 +/-
      0.2% (GLP-1; p = 0.012). In contrast to part A, oral water intake was reduced by
      36% under GLP-1 treatment: 1,848 +/- 331 ml (placebo) vs. 1,181 +/- 177 ml (GLP
      1; p = 0.0414). Three subjects in part B did not finish treatment with GLP-1
      because of diarrhea. Human GLP-1 receptor mRNA expression was highest in the
      proximal human small intestine compared to terminal ileum and colon (p < 0.02).
      CONCLUSIONS: GLP-1 acts on renal tissue reducing sodium absorption, probably via
      similar sodium transporters, which also may be localized in the gastrointestinal
      tract. This hypothesis needs to be confirmed by further studies.

PMID- 16809912
TI  - Nutritional support after open liver resection: a systematic review.
AB  - BACKGROUND: Perioperative nutrition in patients with limited liver function after
      partial hepatic resection is still controversial. In particular, the significance
      of perioperative total enteral nutrition remains unresolved. The aim of this
      review is to investigate the impact of early postoperative total enteral
      nutrition on convalescence after partial liver resection. MATERIALS AND METHODS:
      In an internet-based Medline-Search (time course: 1960-08/2005) a total of five
      prospective, randomized controlled trials were found comparing the impact of
      enteral and parenteral nutrition after liver resection. After study validity had
      been established, a systematic review was undertaken (odds ratio, 95% confidence
      interval, p < 0.05 level of significance; Review Manager 4.2, The Cochrane
      Collaboration). Primary endpoints were complication rate (infection, organ
      malfunction) and mortality. Standardized immune parameters were also surveyed.
      RESULTS: Statistical analysis showed that enteral nutrition resulted in a
      significantly lower rate (p = 0.04) of wound infection and catheter-related
      complications than parenteral nutrition did. No statistically significant
      differences in mortality due to enteral or parenteral nutrition could be found.
      Patients receiving enteral nutrition showed better postoperative immune
      competence. CONCLUSION: Early enteral nutrition after liver resection is a safe
      procedure. Compared to parenteral nutrition it is associated with a decreased
      incidence of postoperative complications. Facing the inhomogeneity of these
      trials, especially in nutrition protocols and end points, this first systematic
      review stresses the need for an update of the importance of early enteral
      nutrition after liver resection within randomized controlled multicenter trials.

PMID- 16809913
TI  - Combined Thiersch's procedure and subanodermal coagulation for complete rectal
      prolapse in the elderly.
AB  - BACKGROUND: The author describes a modification of Thiersch's procedure in
      patients with complete rectal prolapse by inducing fibrosis at the anal verge
      through circumferential subanodermal coagulation using a radiofrequency device.
      MATERIALS AND METHODS: An Ellman radiofrequency generator was used for
      coagulation. The postoperative events were recorded. The patients were followed
      over a period of 2 years to assess late outcome. RESULTS: Postoperative
      complications were observed in 2 patients. One of these developed suppuration in
      the tract of the encircling wire that needed removal, while the other had a
      recurrence due to loosening of the wire. At a 2-year follow-up, 3 patients
      developed recurrence while 1 had a persistent complaint of fecal incontinence.
      CONCLUSION: This study shows that a combined procedure of radiofrequency
      coagulation followed by Thiersch's circumanal wiring is quick and easy to perform
      with no formidable morbidity in elderly patients who are otherwise considered at
      high risk for definitive surgical procedures.

PMID- 16809914
TI  - Pseudoaneurysm of the splenic artery.

PMID- 16809915
TI  - Results of the combination of open transthoracic esophagectomy with laparoscopic
      gastric tube formation for esophageal cancer.
AB  - BACKGROUND: Postoperative complications after open transthoracic esophagectomy
      could possibly be reduced if the abdominal phase is performed laparoscopically.
      The aim of this study was to investigate the feasibility of laparoscopic
      mobilization of the stomach and gastric tube formation in patients undergoing an
      open transthoracic esophagectomy for cancer. METHODS: Thirteen patients underwent
      an open transthoracic esophagectomy with extended en bloc lymphadenectomy
      combined with laparoscopic gastric tube formation. Clinicopathological data were
      derived from a prospective database and patient files. RESULTS: The median
      operation time was 484 min (range 347-573) and the median intraoperative blood
      loss was 1,500 ml (range 250-3,700). In 2 patients the laparoscopic procedure was
      converted to a laparotomy because of technical difficulties. Median postoperative
      stay in the ICU was 3 days (range 1-8) and median hospital stay was 29 days
      (range 12-104). One patient died in the hospital. Postoperatively 3 patients
      suffered from anastomotic leakage, 5 from pneumonia and 3 from vocal cord palsy.
      CONCLUSIONS: The complication rate was high in this series of patients undergoing
      an open extended transthoracic esophagectomy with laparoscopic mobilization of
      the stomach and gastric tube formation. Laparoscopic mobilization of the stomach
      and gastric tube formation are feasible, but need carefully guided testing before
      this technique can be applied routinely.

PMID- 16809916
TI  - An incomplete congenital septum of the duodenal bulb.

PMID- 16809917
TI  - Life-threatening hemorrhage from adenomas in the liver during pregnancy.

PMID- 16809918
TI  - Implication of pituitary tropic status on tumor development.
AB  - Pituitary tumor initiation and progression are associated with a plethora of
      genetic imbalances. Several genetic abnormalities have been described in
      pituitary tumors, from mutations in intracellular signaling (constitutive
      activation adenylyl cyclase) and growth factor pathways (epidermal growth factor
      receptor [EGFR]) to imbalance in cell cycle regulators (p16, p27, pRb).
      Unfortunately, most of these observations do not provide validated predictors of
      clinical behavior or of recurrence. The pituitary gland is notably plastic, and
      intrinsic and extrinsic stimuli result in profound growth changes ranging from
      hypoplasia to hyperplasia. The impact of pituitary tropic status on influencing
      neoplastic potential is difficult to test in human samples because the gland is
      not readily accessible for ongoing morphological observation. Animal models
      represent a functional approach to testing this hypothesis, and transgenic mouse
      models of pituitary tumor transforming gene (PTTG) inactivation or overexpression
      support the notion that pituitary tropic status directly correlates with
      likelihood for pituitary tumor formation. Understanding the mechanisms underlying
      changes in pituitary plasticity and their relationship to tumor development may
      contribute to the ability of regulating the development and progression of
      pituitary tumors.

PMID- 16809919
TI  - Anterior pituitary cell renewal during the estrous cycle.
AB  - The anterior pituitary gland undergoes a process of cell renewal during the
      estrous cycle. Although the occurrence of proliferation and death of anterior
      pituitary cells at specific stages of the estrous cycle is well known, the
      underlying mechanisms that regulate these processes are still being uncovered. In
      spite of the recognized proliferative effects of estrogens on lactotropes, recent
      evidence shows that estrogens can also trigger antiproliferative and apoptotic
      responses in anterior pituitary cells. In the present review we analyze the
      actions of gonadal steroids on proliferation and death of anterior pituitary
      cells during the estrous cycle and the mediators involved in these actions.
      Estradiol sensitizes anterior pituitary cells not only to mitogenic stimuli but
      also to apoptotic signals and upregulates local synthesis of tropic growth
      factors as well as proapoptotic cytokines. Several growth factors and cytokines
      have been shown to induce estrogen-dependent lactotrope proliferation and death,
      whereas progesterone antagonizes estrogen-induced effects. These locally
      synthesized factors may mediate the effects of gonadal steroids in the process of
      anterior pituitary cell renewal during the estrous cycle.

PMID- 16809920
TI  - Bone morphogenetic protein-4 control of pituitary pathophysiology.
AB  - Bone morphogenetic protein-4 (BMP-4), a member of the transforming growth factor
      Beta(TGF-Beta) family, is overexpressed in different prolactinoma models and
      induces the development of these lineage adenomas. SMAD proteins activated by
      growth factors of the TGF-Beta and BMP family interact with estrogen receptors to
      stimulate the proliferation of prolactin and growth hormone-secreting cells.
      Furthermore, BMP-4 presents differential expression in normal and adenomatous
      corticotropes and inhibitory action on corticotropinoma cell proliferation.
      Moreover, BMP-4 mediates the antiproliferative action of retinoic acid in these
      cells. The present review highlights not only the crucial and opposite role of
      BMP-4 in the progression of pituitary adenomas but also that BMP-4 and retinoic
      acid interaction might serve as a potential new mechanism target for therapeutic
      approaches for Cushing disease.

PMID- 16809922
TI  - Dopaminergic D2 receptor knockout mouse: an animal model of prolactinoma.
AB  - Dopamine receptor type 2 (D2R) knockout mice (KO) have chronic
      hyperprolactinemia, pituitary hyperplasia, and a moderate decrease in MSH
      content. They are also growth retarded evidencing an alteration in the GH-IGF-I
      axis. In D2R KO, lactotropes do not show dense secretory granules but
      degranulated cells and fewer somatotropes, gonadotropes and thyrotropes.
      Prolactin levels are always higher in female than in male knockouts, and in
      accordance, pituitary hyperplasia is observed at 8 months only in females. After
      16 months of age, highly vascularized adenomas develop, especially in females.
      Prominent vascular channels in the hyperplastic and adenomatous pituitaries, as
      well as extravasated red blood cells not contained in capillaries is also a
      common finding. Prolactin is not the factor that enhances the hyperplastic
      phenotype in females while estrogen is a permissive factor. VEGF-A expression is
      increased in pituitaries from D2R KO. VEGF-A is expressed in follicle stellate
      cells. Because D2R receptors are found in lactotropes and not in follicle
      stellate cells, it may be inferred that a paracrine-derived factor from
      lactotropes is acting on follicle stellate cells to increase VEGF-A expression.
      VEGF-A does not induce pituitary cell proliferation, even though it enhances
      prolactin secretion. But it may act on adjacent endothelial cells and participate
      in the angiogenic process that increases the availability of different growth
      factors and mitogens. The D2R knockout mouse represents a unique animal model to
      study dopamine-resistant prolactinomas, and VEGF-A may be an alternative
      therapeutic target in this pathology.

PMID- 16809921
TI  - Genesis of prolactinomas: studies using estrogen-treated animals.
AB  - Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of
      pituitary tumors in humans. Our knowledge of the formation of these tumors is
      limited. Experimental work in animal has uncovered that estradiol exposure leads
      to prolactinoma formation via orchestrated events involving dopamine D2
      receptors, transforming growth factor-beta(TGF-beta) isoforms and their
      receptors, as well as factors secondary to TGF-beta action. Additionally, these
      studies determined that TGF-beta and b-FGF interact to facilitate the
      communication between lactotropes and folliculo-stellate cells that is necessary
      for the mitogenic action of estradiol. The downstream signaling that governs
      lactotropic cell proliferation involves activation of the MAP kinase p44/42
      dependent pathway.

PMID- 16809923
TI  - Vasoinhibins: a family of N-terminal prolactin fragments that inhibit
      angiogenesis and vascular function.
AB  - Antiangiogenic molecules derived from prolactin (PRL) are not a single entity,
      but rather a family of peptides with different molecular masses, all containing
      the N-terminal region of PRL. Cleavage of PRL by cathepsin-D or by matrix
      metalloproteases generates N-terminal fragments that act on endothelial cells to
      suppress vasodilation and angiogenesis and promote vascular regression. N
      terminal PRL fragments have been identified in cartilage and retina, where
      angiogenesis is highly restricted. In vivo experiments demonstrate that these PRL
      fragments exert a tonic and essential suppression of retinal blood vessel growth
      and dilation. Similar PRL fragments have been detected in the pituitary gland, a
      highly vascularized organ where the control of vascular growth may differ from
      that in tissues where angiogenesis is highly restricted. We have previously
      proposed the name vasoinhibins to describe the collection of N-terminal PRL
      fragments having blood vessel-blocking activity, and here we discuss their
      promise as factors to control vascular function in health and disease.

PMID- 16809924
TI  - Molecular mechanisms of pituitary differentiation and regulation: implications
      for hormone deficiencies and hormone resistance syndromes.
AB  - During the last century, the questions posed by scientists and clinicians on
      pituitary function have led to new concepts about the mechanisms of hormone
      action and cell differentiation. In particular, the advent of molecular genetics
      and the cloning of pituitary hormone coding genes followed by discovery of their
      regulators during the last 20 years has provided tremendous insight into the
      pathophysiological bases of hormone deficit and excess, as well as offering novel
      therapeutic opportunities. Most insight was gained through the identification of
      transcription factors that control the program of pituitary organogenesis and
      cell differentiation; it is indeed the normal developmental program controlled by
      these transcriptional regulators that is perturbed in inherited forms of hormone
      deficiency. This review will summarize our current understanding of these
      processes and their implications for hormone deficiency and hormone resistance
      syndromes from a developmental perspective.

PMID- 16809925
TI  - Long-term follow-up of prolactinomas: should dopamine agonist treatment be life
      long?
AB  - Dopamine agonists (DA) are the treatment of choice for both micro- and
      macroadenomas. However, the only limitation of this treatment is the low rate of
      cure, as well as the long-term therapy usually seen in most patients. In our
      data, 16% of patients with prolactinomas remained normoprolactinemic after DA
      withdrawal. The duration of treatment before DA discontinuation was the only
      statistically significant factor in the cured versus the remission groups. Taking
      into account all the data from the published series, the rate of cure after DA
      withdrawal ranged from 5 to 37.5%, and only 1% of tumor regrowth was observed in
      spite of the high recurrence rate. The board of experts provided recommendations
      based on the revision of all the data presented at this consensus meeting:
      dopamine agonists can be routinely withdrawn in patients receiving DA. The length
      of treatment recommended is 1-3 years, during which DA may be tapered off, and
      serum PRL levels should be monitored. Tumor disappearance on MRI and the levels
      of PRL under the lower dose of DA will be determinant for DA withdrawal. Factors
      influencing prolactinomas outcome are analyzed in the discussion.

PMID- 16809926
TI  - Ghrelin: from somatotrope secretion to new perspectives in the regulation of
      peripheral metabolic functions.
AB  - Ghrelin, a peptide predominantly produced by the stomach, has been discovered as
      natural ligand of the GH secretagogue (GHS) receptor type 1a (GHS-R1a),
      suggesting the existence a new endogenous modulator of somatotrope secretion.
      Subsequently, ghrelin turned out to exert pleiotropic actions, consistent with
      the widespread distribution of ghrelin and GHS-R expression in central and
      peripheral tissues. Despite that the binding to GHS-R1a requires ghrelin to be
      acylated in serine 3, some ghrelin actions are independent of such acylation;
      thus suggesting the possibility of the existence of other GHS-R subtypes. Ghrelin
      secretion (70% in its unacylated form) is mainly under metabolic control being
      modulated by glucose, insulin and feeding. On the other hand, ghrelin influences
      energy metabolism acting both as a central orexigenic factor and directly on the
      endocrine pancreas, liver and adipose tissue. Recently, another gastric hormone
      derived from the same ghrelin gene has been isolated and named obestatin.
      Obestatin in rats resulted in reduced food intake, jejunal contraction and body
      weight gain, via specific distinct receptors. Thus, all these data indicate that
      we are exploring a very complex system deeply involved in the modulation of
      metabolic functions, whose understanding will probably increase our knowledge
      about diabetes mellitus and the metabolic syndrome.

PMID- 16809927
TI  - Regulating of growth hormone sensitivity by sex steroids: implications for
      therapy.
AB  - Growth hormone (GH) is an important regulator of body composition, reducing body
      fat by stimulating fat oxidation and enhancing lean body mass by stimulating
      protein accretion. The emergence of differences in body composition between the
      sexes during puberty suggests sex steroids modulate the action of GH. Work from
      our laboratory have investigated the influence of estrogens and androgens on the
      metabolic actions of GH in human adults. The liver is an important site of
      physiological interaction as it is a sex steroid responsive organ and a major
      target of GH action. Estrogen, when administered orally impairs the GH-regulated
      endocrine and metabolic function of the liver via a first-pass effect. It reduces
      circulating IGF-I, fat oxidation and protein synthesis, contributing to a loss of
      lean and a gain of fat mass. These effects occur in normal and in GH-deficient
      women and are avoided by transdermal administration of physiological doses of
      estrogen. In contrast, studies in hypopituitary men indicate that testosterone
      enhances the metabolic effects of GH. Testosterone alone stimulates fat oxidation
      and protein synthesis, both of which are enhanced by GH. Studies in GH deficiency
      adults have consistently reported women to be less sensitive to GH than men. In
      summary, estrogens and androgens exert divergent effects on the action of GH. The
      results provide an explanation for sexual dimorphism in body composition in
      adults and the gender-related response to GH replacement in hypopituitary
      subjects. In the management of hypopituitarism, estrogens should be administered
      by the parenteral route in women and testosterone be replaced in men to optimize
      the benefits of GH replacement.

PMID- 16809928
TI  - Acromegaly: molecular expression of somatostatin receptor subtypes and treatment
      outcome.
AB  - About a third of acromegalic patients are resistant to the currently commercially
      available somatostatin analogs (SA) octreotide and lanreotide. Such resistance is
      related to an overall reduction of somatostatin receptor (SSTR) density or to a
      differentiated expression of SSTR subtypes. There are five known SSTR subtypes.
      SSTR2 and SSTR5 are usually expressed in GH-secreting pituitary tumors, and both
      octreotide and lanreotide bind preferentially to SSTR2 and, to a lesser extent,
      to SSTR5. SA inhibitory effects on GH secretion and tumor cell proliferation can
      occur together or be dissociated events, depending on the tumor expression of
      SSTR subtypes involved in each mechanism. The development of specific
      somatostatin subtypes analogs, mainly for SSTR5, of a SSTR2-SSTR5 bispecific
      compound, and of a "universal" analog with high affinity to SSTR1, 2, 3, and 5
      showed preliminary, albeit promising results for the treatment of resistant
      somatotropic adenomas.

PMID- 16809929
TI  - Gene therapy in the neuroendocrine system.
AB  - The implementation of experimental gene therapy in animal models of
      neuroendocrine diseases is an area of growing interest. In the hypothalamus,
      restorative gene therapy has been successfully implemented in Brattleboro rats,
      an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, and
      in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor
      mutations that render them obese, hyperphagic and hyperinsulinemic. In the above
      models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin,
      respectively, were stereotaxically injected in the relevant hypothalamic regions.
      In rats, aging brings about a progressive degeneration and loss of hypothalamic
      tuberoinfundibular dopaminergic (TIDA) neurons, which are involved in the tonic
      inhibitory control of prolactin secretion and lactotropic cell proliferation.
      Stereotaxic injection of an adenoviral vector expressing insulin-like growth
      factor I corrected their chronic hyperprolactinemia and restored TIDA neuron
      numbers. Spontaneous intermediate lobe pituitary tumors in a retinoblastoma (Rb)
      gene mutant mouse were corrected by injection of an adenoviral vector expressing
      the human Rb cDNA and experimental prolactinomas in rats were partially reduced
      by intrapituitary injection of an adenoviral vector expressing the HSV1-thymidine
      kinase suicide gene. These results suggest that further implementation of gene
      therapy strategies in neuroendocrine models may be highly rewarding.

PMID- 16809930
TI  - Ectopic ACTH syndrome.
AB  - Ectopic adrenocorticotropin secretion (EAS) accounts for 10-15% of cases of
      Cushing's syndrome and comprises a spectrum of tumours from undetectable isolated
      lesions to widespread metastatic and aggressive malignancies. EAS is often
      associated with severe hypercortisolaemia causing hypokalaemia, diabetes,
      generalized infections, hypertension and psychotic reactions. Surgical resection
      of the primary lesion, achievable with a curative intent in about 40% of patients
      with EAS, is associated with complete remission in up to 80% of such cases. It is
      therefore mandatory to localize the source of ectopic ACTH hypersecretion in
      order to stage the disease and adopt optimal treatment modalities. Modern cross
      sectional imaging techniques can identify the majority of the ACTH secreting
      lesions, either initially or at follow-up reassessment. However, in approximately
      10-20% of patients with EAS, the source of ACTH hypersecretion remains occult in
      spite of extensive investigation and prolonged followup. In such cases, control
      of the hypercortisolemia can be achieved with long-term adrenolytic medication.
      When conditions require a prompt and definitive resolution of the
      hypercortisolaemia (i.e. as in pregnancy), bilateral adrenalectomy remains an
      alternative option. This review focuses on the clinical features, diagnostic
      pitfalls, management and long-term followup of the EAS based on the extensive
      experience of major referral centres.

PMID- 16809931
TI  - Estrogens and neuroendocrine hypothalamic-pituitary-adrenal axis function.
AB  - The function of the HPA axis is subject to regulation by many factors, which
      achieve relevance under normal and pathological conditions. In the case of aging,
      this period of life is associated with disturbances of the HPA axis and signs of
      hippocampal vulnerability. We examined 20-month-old male rats, in which
      abnormalities of the HPA axis included altered response to stress, reduced
      effectiveness of the steroid negative feedback and low expression of hippocampal
      glucocorticoid receptors (GR). Estrogen treatment of aging rats normalized the
      response to stress, restored the dexamethasone inhibition of the stress response
      and increased GR density in defined hippocampal areas. Although estrogens could
      influence the hippocampus of aging animals directly, their effects could be also
      mediated by estrogen-sensitive forebrain cholinergic neurons projecting to the
      hippocampus. Additionally, estrogens normalized the deficient granule cell
      proliferation that aging mice present in the dentate gyrus, and attenuated
      several markers of hippocampal aging, such as astrocytosis, high lipofucsin
      content and neuronal loss in the hilus of the dentate gyrus. These effects may be
      important for the regulation of the HPA axis, in the context that hippocampal
      function as a whole was normalized by estrogen action. Therefore, estrogens are
      powerful neuroprotectants in cases of hippocampal dysfunction, and as part of
      this effect, they contribute to stabilize the function of the HPA axis.

PMID- 16809932
TI  - New aspects in the diagnosis and treatment of Cushing disease.
AB  - Cushing disease, which is caused by the excessive production of ACTH, is a rare
      and complex endocrine disorder that still represents a major challenge for the
      physician in terms of accurate diagnosis and efficient treatment. Diagnosing
      Cushing syndrome and its etiology is an elaborate procedure and no single test is
      sensitive and specific enough to provide sufficient accuracy. Therefore, an
      ordered cascade of tests is necessary recommended by a consensus statement in
      2002. The proposed diagnostic algorithm will be summarized in the following
      section. In the absence of efficient drug therapy, transsphenoidal resection of
      the pituitary adenoma is the treatment of choice for the reduction of ACTH
      secretion. However, not all patients can be cured by surgery. In the present
      article, we examine recent studies that have investigated the therapeutic
      potential of new generations of drugs for the treatment of Cushing disease such
      as cabergoline and SOM230. The role of nuclear receptors: retinoic acid receptors
      and peroxisome proliferator-activated receptor-gamma as new approaches for
      treating pituitary tumors is also discussed.

PMID- 16809933
TI  - Pilot phase 2 trial of 4 months of maintenance pegylated liposomal Doxorubicin in
      patients with advanced ovarian cancer after complete response to platinum and
      Paclitaxel-based chemotherapy.
AB  - BACKGROUND/AIMS: Stages III and IV ovarian and peritoneal cancer patients are
      commonly treated with combination chemotherapy after surgical debulking. This
      phase II trial investigated the use of pegylated liposomal doxorubicin as
      consolidation chemotherapy for these patients. METHODS: Women with stage III or
      IV ovarian or primary peritoneal carcinoma demonstrating no clinical evidence of
      disease after primary therapy were eligible for enrollment. Patients received 4
      cycles of 40 mg/m(2) IV of pegylated liposomal doxorubicin every 28 days.
      RESULTS: Twelve patients were enrolled. There were 6 stage IIIC and 6 stage IV
      patients. Ten patients received 4 cycles. Two patients had dose limiting skin
      toxicity manifest as hand-foot syndrome and received only 3 cycles. Forty-six of
      a planned 48 cycles were administered. Median disease-free survival from
      registration is 10 months with a mean of 18 months. Median overall survival has
      not yet been reached. Four patients are disease-free, two have relapsed and six
      have died from disease progression. CONCLUSION: Pegylated liposomal doxorubicin
      is a well-tolerated choice for consolidation chemotherapy in patients with
      ovarian or primary peritoneal carcinoma.

PMID- 16809934
TI  - Amantadine resistance among porcine H1N1, H1N2, and H3N2 influenza A viruses
      isolated in Germany between 1981 and 2001.
AB  - This study was designed to gain insight into amantadine susceptibility of porcine
      influenza A viruses isolated in Germany between 1981 and 2001. The 12 studied
      H1N1, H1N2, and H3N2 porcine influenza virus strains were isolated in chicken
      eggs and passaged once in MDCK cells. Plaque reduction assays were applied to
      examine virus susceptibility to amantadine. Genotyping was used to confirm drug
      resistance. In the results of these antiviral studies, only 3 of the 12 isolates
      were shown to be amantadine-susceptible. All resistant strains contained the AA
      substitutions G16E, S31N, and R77Q in the membrane protein 2 (M2). Additionally,
      L27A was detected in two H1N1 strains. S31N and/or L27A are well-known amino acid
      substitutions in M2 that confer amantadine resistance. The role of the pig as an
      intermediate host of avian and human influenza A viruses, the possible
      involvement of genetic reassortment, and the high incidence of naturally
      amantadine-resistant porcine influenza A viruses suggest a real risk of emergence
      of amantadine resistant human viruses. Therefore, drug susceptibility monitoring
      appears to be warranted for effective application of those drugs.

PMID- 16809935
TI  - Oxidative stress in vero cells infected with vesicular stomatitis virus.
AB  - Viral-induced apoptosis might be mediated by oxidative stress. It has already
      been described that cell death in vesicular stomatitis virus (VSV)-infected cells
      occurs by apoptosis. In this study, oxidative stress parameters present in VSV
      infected Vero cells were analyzed. Lipid peroxides (LP) were evaluated in
      cellular extracts and expressed as thiobarbituric acid-reactive substances. LP
      levels exhibited a rise at different times post infection, according to the
      multiplicity of infection (MOI), while the presence of cycloheximide determined a
      reduction on LP. Also, an increase in protein degradation products and a decrease
      in polyunsaturated fatty acids content was observed, indicating that cellular
      proteins and lipids began to be susceptible to degradation during VSV infection.
      In addition, we analyzed cell viability of VSV-infected Vero cells, which were
      incubated in the presence of butylated hydroxyanisole. This antioxidant was able
      to protect Vero cells, at least at MOIs assayed in this study, and to reduce
      viral yield only when VSV infection was done at MOI 0.05. Further, superoxide
      dismutases, which occupy the first step within the antioxidant enzyme cascade,
      also exhibit a rise in VSV-infected Vero cells, at different MOI. These results
      suggest that both an oxidative stress and an antioxidative cell response precede
      the induction of apoptosis by VSV.

PMID- 16809936
TI  - Enhanced induction of SARS-CoV nucleocapsid protein-specific immune response
      using DNA vaccination followed by adenovirus boosting in BALB/c mice.
AB  - OBJECTIVE: To investigate immunogenicity in the induction of humoral and cellular
      immune responses to genetic vaccines of the recombinant severe acute respiratory
      syndrome-associated coronavirus (SARS-CoV)-N gene expressing the same protein
      plasmid, pcDNA3.1-N, and replication-defective adenoviral vector, rAd-N, in a
      pcDNA3.1-N prime-rAd-N boost regimen and the reverse sequence in a rAd-N prime
      pcDNA3.1-N boost regimen. METHOD: After the mice had been immunized
      intramuscularly and/or intraperitoneally with pcDNA3.1-N and rAd-N in prime
      triple boost immunization, humoral and cellular immune responses were detected.
      RESULTS: After detection, different levels of anti-N humoral and cellular
      responses are shown compared to controls. The humoral immune response was induced
      more effectively by the DNA priming and recombinant adenovirus boosting regimen
      and the reverse sequence of heterogeneous combinations. There is a significant
      difference between heterogeneous and homologous vaccinations. However, the
      cytotoxic T lymphocyte (CTL) response was not significantly altered by the
      different prime-boost immunizations or the recombinant adenovirus of pcDNA3.1-N
      prime-rAd-N boost regimen alone, but lymphoproliferation and interferon-gamma
      (IFN-gamma) secretion were all enhanced by heterologous combination immunizations
      compared to homologous combinations. For the reverse sequence immunization
      regimen, lymphoproliferation, IFN-gamma and CTL responses were all significantly
      weaker compared with pcDNA3.1-N prime-rAd-N boost regimen. CONCLUSION: Taken
      together, of all the combinations, the prime-triple boost immunization of
      pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N can effectively induce SARS-CoV-N-specific
      and strong humoral and cellular immune responses in mice. The present results
      suggest that DNA immunization followed by recombinant adenovirus boosting could
      be used as a potential SARS-CoV vaccine in the induction of an enhanced humoral
      and cellular immune response.

PMID- 16809937
TI  - Propionyl-L-carnitine therapy: effects on endothelin-1 and homocysteine levels in
      patients with peripheral arterial disease and end-stage renal disease.
AB  - BACKGROUND/AIMS: Recent data have addressed the issue of higher levels of
      homocysteine (Hcy) and endothelin-1 (ET-1) in end-stage renal disease (ESRD) that
      may be considered an independent predictor for cardiovascular disease. The
      prevalence of peripheral arterial disease (PAD) in patients with ESRD has been
      reported to be relevant, highlighting its clinical importance. We aimed to
      explore the therapeutic role of propionyl-L-carnitine (PLC) in hemodialysis
      patients with PAD by measuring ankle/brachial index (ABI), ET-1 and Hcy. DESIGN:
      Randomized, double-blind, placebo-controlled trial. METHODS: Sixty-four patients
      on hemodialysis with chronic renal insufficiency and PAD were assigned to receive
      either intravenous PLC (600 mg) or placebo 3 times weekly for 12 months. The ABI
      and plasma levels of ET-1 and Hcy were measured at baseline, 6 and 12 months.
      RESULTS: In the PLC-treated group, progressive increases in ABI were observed,
      while in the placebo group the reverse trend was seen. Highly significant and
      progressive reductions in plasma levels of ET-1 and Hcy, compared to baseline,
      were also seen in the PLC-treated group. CONCLUSIONS: Hemodynamic flow,
      endothelial profile and Hcy levels were ameliorated by the administration of PLC
      in hemodialysis patients with ESRD and PAD.

PMID- 16809938
TI  - Psychometric evaluation of the Brief Cancer Impact Assessment among breast cancer
      survivors.
AB  - OBJECTIVES: The increasing number of cancer survivors brings greater attention to
      the biopsychosocial impact of surviving cancer. Instruments exist that measure
      quality of life (QOL), symptoms, and specific types of functioning after cancer;
      however, a reliable and valid assessment of the perceived impact of cancer (IOC)
      on the life plans and activities of cancer survivors has been missing. This study
      evaluated the psychometric properties of the 16-item Brief Cancer Impact
      Assessment (BCIA). METHODS: Factor analysis with Promax oblique rotation
      established the factor structure of the BCIA in 783 ethnically diverse breast
      cancer survivors, >or=2 years after diagnosis. Construct validity was assessed by
      comparing factor-based scale means by demographic and treatment characteristics,
      and correlating scales with psychosocial and health-related QOL scales. RESULTS:
      Factor analysis revealed four factors measuring the IOC on caregiving and
      finances, exercise and diet behaviors, social and emotional functioning, and
      religiosity. Scale scores differed by demographic and treatment characteristics
      according to expectations, and the pattern of correlations with psychosocial and
      health-related QOL generally supported the construct validity of the scales.
      CONCLUSION: Including the BCIA with measures of QOL, symptoms, and functioning
      will allow researchers to gain a more comprehensive assessment of the
      biopsychosocial IOC in survivors.

PMID- 16809939
TI  - Combined detection of CEA, CK-19 and c-met mRNAs in peripheral blood: a highly
      sensitive panel for potential molecular diagnosis of non-small cell lung cancer.
AB  - OBJECTIVE: Detection of tumor-related mRNA in blood has become a potential cancer
      diagnostic approach. However, the sensitivity of single-marker assays is not high
      enough for clinical applications. The present study was aimed to evaluate the
      efficacy of a multimarker panel for molecular diagnosis of non-small cell lung
      cancer (NSCLC). METHODS: Carcinoembryonic antigen (CEA), cytokeratin 19 (CK-19),
      c-met and heterogeneous nuclear ribonucleoprotein (hnRNP) B1 mRNAs were
      quantified by quantitative real-time reverse transcriptase polymerase chain
      reaction in 34 tumor tissues and 69 peripheral blood samples of NSCLC patients.
      RESULTS: All four markers displayed high overexpression rates (range 82.3-97.1%)
      in NSCLC tumors. When used as single markers in blood for NSCLC diagnosis, CEA,
      CK-19, c-met and hnRNP B1 could only reach sensitivities of 52.2, 50.7, 42 and
      17.4%, respectively. However, the sensitivity was enhanced up to 85.5% when CEA,
      CK-19 and c-met were combined in a 3-marker panel. Moreover, the expression of c
      met and hnRNP B1 in blood was significantly correlated with patients'
      pathological stages. CONCLUSIONS: The combined detection of CEA, CK-19 and c-met
      mRNAs in blood provided a valuable tool for molecular diagnosis of NSCLC. In
      addition, our results also suggested that hnRNP B1 was not a valuable diagnostic
      marker but a potential prognostic marker for NSCLC.

PMID- 16809940
TI  - Defective expression of HRK is associated with promoter methylation in primary
      central nervous system lymphomas.
AB  - OBJECTIVES: Recently, it has been reported that expression of the HRK gene was
      significantly reduced by hypermethylation in astrocytic tumors. Our aim is to
      verify the alterations in the HRK gene in primary central nervous system
      lymphomas (PCNSLs). METHODS: We analyzed the hypermethylation status and
      expression of the gene and 12q13.1 loss of heterozygosity in 31 PCNSLs. RESULTS:
      A total of 13 PCNSLs (31%) demonstrated hypermethylation in either the promoter
      or exon 1; loss of HRK expression was immunohistochemically observed in 9 tumors
      and was significantly associated with promoter methylation. In addition, higher
      apoptotic counts were associated with HRK positivity. PCNSLs with HRK methylation
      also showed methylation of multiple genes, such as p14ARF, p16INK4a, RB1, p27Kip1
      and O6-MGMT. Patients with tumors demonstrating concurrent methylation of more
      than half of their genes demonstrated significantly poorer survival and earlier
      recurrence. Hypermethylation of the HRK promoter alone was not associated with
      overall outcome, but relapse-free survival was significantly shorter.
      CONCLUSIONS: Our findings suggest that transcriptional repression of HRK is
      caused by promoter hypermethylation in PCNSL, and that the loss of HRK associated
      with the methylation profile of other genes is a potential step in the modulation
      of cellular death by apoptosis during PCNSL tumorigenesis.

PMID- 16809941
TI  - Expression of Oct4, a stem cell marker, in the hamster pancreatic cancer model.
AB  - BACKGROUND: Oct4 has been shown to present a stem cell marker that is expressed
      in embryonic cells and in germ cell tumors. Recently, its expression in a few
      human tissues and cancer cells has been reported. Because in the hamster
      pancreatic cancer model most tumors develop from within islets presumably from
      stem cells, we investigated the expression of Oct4 in this model. METHODS: Two
      normal pancreases and 15 pancreatic cancers induced by N-nitrosobis(2
      oxypropyl)amine (BOP) were processed for immunohistochemistry using a monoclonal
      Oct4 antibody at a concentration of 1:500. RESULTS: In the normal pancreas, Oct4
      was expressed only in islet cells in a diffuse cytoplasmic pattern. No nuclear
      staining was found in any cells. In 14 of the pancreatic cancers, nuclear
      staining was detected in many cells or in small foci. Diffuse cytoplasmic but no
      nuclear staining was found in one tumor and a mixed Golgi type and nuclear
      staining in two cases. Nuclear staining was also identified in early intrainsular
      ductular and in Ca in situ lesions. CONCLUSIONS: BOP reactivates the Oct4 gene
      and can be considered an early tumor marker in this model.

PMID- 16809942
TI  - The 5th International Symposium on Inherited Diseases of the Pancreas.

PMID- 16809943
TI  - 'Enjoy Thinking, Even if It Is Hard Work': an interview with Professor Gunther
      Kloeppel. [Interview by Martin E. Fernandez-Zapico].
AB  - Professor Gunther Kloeppel is a distinguished pancreatic pathologist, recognized
      the world over for his enormous contribution to the understanding of the
      pathogenesis of different pancreatic diseases. In the current article, Prof.
      Kloeppel, a role model for establishing a productive academic career, gives
      advice to junior investigators starting in the field of pancreatic research.

PMID- 16809945
TI  - [Pneumatosis intestinalis and hepatic portal venous gas caused by necrotizing
      colitis].

PMID- 16809946
TI  - [Mucosal restitution].
AB  - The repair of superficially damaged intestinal epithelium is initiated by
      restitution. Restitution is the covering of damaged area by the movement of
      neighboring epithelial cells without cell proliferation. Phenotypic switching of
      cells (epithelial-mesenchymal transition) is necessary for the cell movement and
      this process is controlled by complex intracellular signaling pathways conducting
      dynamic remodeling of actin cytoskeleton. Restitution is regulated by a variety
      of cytokines and growth factors, and is modulated by integrin-dependent
      interactions with the extracellular matrix. Understanding the restitution process
      suggests several possible therapeutic strategies to enhance gastrointestinal
      wound healing.

PMID- 16809947
TI  - [The effects of probiotics on symptoms of irritable bowel syndrome].
AB  - BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal
      (GI) tract disorder that has heterogeneous clinical presentations such as
      abdominal pain, diarrhea, constipation, and abdominal distension. It is known
      that several mechanisms are involved in the pathogenesis of IBS. Probiotics may
      target one or more pathophysiologic pathways in IBS and may improve the symptoms
      of IBS. However, the results of studies about probiotics on IBS are
      controversial. Therefore, the aim of this study was to evaluate the effect of
      probiotics on GI symptoms and intestinal gas volume changes in patients with IBS.
      METHODS: Forty patients were randomly allocated to be treated with Medilac DS
      (Bacillus subtilis, Streptococcus faecium) (n=20) or placebo (n=20) in a double
      blind, prospective manner. The change in intestinal gas volume and symptom scores
      after 4-week treatment were evaluated for the efficacy. RESULTS: There was no
      significant difference in bloating, frequency of gas expulsion, frequency of
      defecation, and hardness of stool before and after the treatment. However, the
      severity of abdominal pain and the frequency of abdominal pain decreased
      significantly in Medilac DS group (2.4+/-1.3 cm/day --> 1.6+/-1.6 cm/day, 1.7+/
      1.3/day --> 1.0+/-1.0/day) (p=0.044, p=0.038), but not in placebo group (2.1+/
      2.0 cm/day --> 1.8+/-2.1 cm/day, 1.3+/-1.2/day --> 1.4+/-1.9/day). In both
      groups, intestinal gas volume at baseline, after 2-week treatment, and after 4
      week treatment did not show significant change. Medilac DS was well tolerated
      without adverse events. CONCLUSIONS: Medilac DS is a safe and useful probiotic
      agent for the treatment of abdominal pain in patients with IBS.

PMID- 16809948
TI  - [The usefulness of mesalazine suppositories for the treatment of lymphoid
      follicular proctitis].
AB  - BACKGROUND/AIMS: Lymphoid follicular proctitis (LFP) is an uncommon inflammatory
      condition confined to the rectum. Patients with LFP constitute a special group
      with clinical, endoscopic, and histological features unrelated to other types of
      inflammatory bowel diseases, and have been reported to be refractory to local
      steroid and/or oral sulfasalazine therapy. The aim of this study was to clarify
      whether mesalazine suppositories have a therapeutic effect in LFP. METHODS: The
      histologic slides of 8 cases indexed in our pathology files as "lymphoid
      follicular proctitis of the rectal mucosa" from January 2001 to November 2003
      were reviewed retrospectively. RESULTS: The most common symptom in the patients
      with LFP was rectal bleeding. The endoscopic mucosal changes were discontinuous,
      sparing whole circumferential involvement, and were strictly confined to the
      rectum. Average period of medication was 12 months. All the symptomatic patients
      with LFP responded to mesalazine suppository therapy. In addition, these patients
      did not progress to other disease including ulcerative proctitis or lymphoma.
      CONCLUSIONS: Mesalazine suppository treatment is a useful therapeutic option for
      symptomatic patients with LFP.

PMID- 16809949
TI  - [Clinicopathological features and differences of p53 and Ki-67 expression in
      adenosquamous and squamous cell carcinomas of the stomach].
AB  - BACKGROUND/AIMS: This study reviews the clinicopathological features, prognosis,
      and differences in the expression of p53 and Ki-67 immunochemical staining in
      squamous cell and adenosquamous carcinoma of the stomach. METHODS: From January
      1995 to June 2005, 2,282 cases of gastric carcinoma were resected surgically in
      our hospital and 191 additional cases were resected by endoscopic mucosal
      resection. Retrospective pathologic review and immunochemical staining of p53 and
      Ki-67 were performed. RESULTS: The study consists of eight cases (0.032%) of
      primary squamous cell carcinoma (one case) and adenosquamous carcinoma (seven
      cases) without early gastric cancer. Six cases (75.0%) were male and two cases
      were female. The mean age was 66 year-old. The clinical presentation and physical
      findings did not differ from those of adenocarcinoma. The mean tumor size was
      5.2+/-1.7 cm. Macroscopically, five were Borrmann type 3 (62.5%) and three were
      type 2. At the initial diagnosis, six (75%) were stage IV based on TNM tumor
      staging. Six cases (75%) progressed despite the therapy while two cases responded
      to the treatment. The median survival time was 11.0 months (range 4.3+/-17.7).
      Overexpression of p53 was seen in five cases (62.5%) and their survival was poor
      when compared to the p53-negative group (p=0.04). The mean Ki-67 labeling index
      was 70.0+/-20.8%, and was not associated with p53 staining (p<0.05). CONCLUSIONS:
      Adenosquamous and squamous cell carcinoma of the stomach are very rare. They tend
      to be at advanced stages on initial diagnosis, and progress rapidly. They show
      p53 protein overexpression and high Ki-67 labeling index, which might be related
      to poor prognosis.

PMID- 16809950
TI  - [Association of hepatic iron deposition and serum iron indices with hepatic
      inflammation and fibrosis stage in nonalcoholic fatty liver disease].
AB  - BACKGROUND/AIMS: Nonalcoholic steatohepatitis can develop from nonalcoholic fatty
      liver and progress to severe liver disease such as cirrhosis. The mechanism
      determining the progression from fatty liver to steatohepatitis is unknown. Iron
      is suspected to enhance hepatic damage associated with nonalcoholic fatty liver
      disease (NAFLD). The aims of this study were to evaluate the relationship of
      serum iron indices and hepatic iron deposition with hepatic fibrosis or
      inflammation, and to assess whether the increased hepatic iron deposition is an
      independent predictor of progression to liver injury. METHODS: The biochemical
      and histopathological data of thirty-nine patients with NAFLD were analyzed.
      Liver biopsy findings were graded according to the method described by Brunt, et
      al. Hepatic iron concentration was available in 29 of 39 patients. RESULTS: The
      mean hepatic iron concentration and hepatic iron indices were 1,349+/-1,188
      microg/g dry weight and 0.9+/-0.7 microg/g/age. Serum ferritin and body mass
      indices were associated with hepatic inflammation (p=0.001, p=0.006) and fibrosis
      (p=0.005, p=0.013). Hepatic iron concentration and hepatic iron index were not
      associated with hepatic inflammation and fibrosis. Multivariate analysis did not
      identify serum ferritin or body mass index as an independent predictor of liver
      injury. CONCLUSIONS: Hepatic iron deposition shows no association with the degree
      of hepatic inflammation or fibrosis. Hepatic iron is not an independent predictor
      of hepatic injury in patients with NAFLD.

PMID- 16809951
TI  - [The long-term follow-up results after steroid treatment in patients with
      autoimmune chronic pancreatitis].
AB  - BACKGROUND/AIMS: Autoimmune chronic pancreatitis (AIP) is a clinically attractive
      entity because of its dramatic response to steroid therapy. But the long-term
      results after steroid therapy have not been reported yet in Korea. The purpose of
      this study was to assess the long-term results and prognosis after steroid
      therapy in patients with AIP. METHODS: We retrospectively analyzed the clinical,
      radiologic, and laboratory features and evaluated clinical outcomes in 19
      patients with AIP who have been treated with oral corticosteroid. All patients
      were initially treated with prednisolone (30-40 mg/d) for 1 or 2 months. After
      the confirmation of clinical improvement in radiologic imaging and laboratory
      findings, the daily dose of prednisolone was then gradually tapered by 5-10 mg
      per month to the maintenance dose (2.5-7.5 mg/d). RESULTS: All the patients
      showed normalization or marked improvement in symptoms, laboratory and imaging
      findings after steroid therapy. There were 4 cases (21%) of recurrence during the
      mean follow-up period of 27 months. All the patients with recurrence responded to
      oral steroid again. Among the 10 patients with diabetes mellitus, seven patients
      were able to stop or reduce the medication for diabetes after completion of
      steroid therapy. The biliary stents were additionally inserted in 10 patients who
      showed distal common bile duct stricture and obstructive jaundice. The
      accompanying autoimmune diseases were also improved with oral corticosteroid.
      CONCLUSIONS: Steroid therapy is very effective for AIP and is also effective in
      the cases of recurrence. A definitive protocol of steroid therapy for AIP should
      be established in the future.

PMID- 16809952
TI  - Localized esophageal ulcerations after CyberKnife treatment for metastatic
      hepatic tumor of colon cancer.
AB  - CyberKnife is an image-guided robotic system designed for stereotactic
      radiosurgery. It uses the combination of robotics and image guidance to deliver
      concentrated and accurate beams of radiation to intracranial and extracranial
      targets. Although the frameless nature of the CyberKnife allows tumors in the
      chest and abdomen to be treated as well, complications associated with CyberKnife
      treatment have not been established yet due to its short clinical experience. We
      describe a case of localized esophageal ulcerations after CyberKnife treatment
      for metastatic hepatic tumor of colon cancer.

PMID- 16809953
TI  - [A case of peripheral ischemic complication after terlipressin therapy].
AB  - Hepatorenal syndrome is a severe complication of cirrhosis, leading to death in
      more than 90% of cases in the absence of liver transplantation. Several
      treatments have been attempted as a bridge to liver transplantation. Among such
      treatments, terlipressin is a nonselective V1 vasopressin agonist. When comparing
      with ornipressin, it is known to have a similar vasoconstricting potency, but
      much less ischemic complication. We report a case of gangrene on toes and
      necrosis on the infusion site of left hand which developed after the use of
      terlipressin due to hepatorenal syndrome in a 41-year-old-man with liver
      cirrhosis. Ischemic complication of terlipressin is rare and there has been no
      case report in Korea. Although it is rare, we must pay attention to the
      peripheral ischemic complication of terlipressin.

PMID- 16809954
TI  - [A case of sarcomatoid hepatocellular carcinoma in a young female without risk
      factor].
AB  - A previously healthy 22-year-old woman was admitted with a complaint of right
      upper quadrant abdominal pain for 2 weeks. Her past history was not remarkable.
      On admission, HBsAg and anti-HCV were negative and alpha-FP was within normal
      range. Abdominal sonography and CT showed a mass in liver measuring 10 x 11 cm
      with features of central necrosis and hemorrhage. On 6th hospital day,
      hemoperitoneum developed suddenly. She underwent emergency laparotomy and
      trisegmentectomy. Intraoperative finding revealed a hemoperitoneum with a tumor
      filled with liquefied necrotic tissues. Microscopically, the tumor was mostly
      composed of pleomorphic spindle cells with abundant anastomosing vascular
      channels and partly composed of tumor cells with trabecular arrangement. On
      immunohistochemical staining, tumor cells reacted with cytokeratin and vimentin,
      while CD34 and hepatocyte staining revealed negative. She died 2 months after the
      operation. We report a case of rapidly deteriorated primary sarcomatoid
      hepatocellular carcinoma in a young female without any risk factor.

PMID- 16809955
TI  - [Clinical improvement of severe ulcerative colitis after incidental appendectomy:
      a case report].
AB  - Recent reports have demonstrated a negative association between appendectomy and
      ulcerative colitis. Many retrospective studies have shown that appendectomy
      appears to be protective against ulcerative colitis. Although the function of
      appendix is not known, all these studies have suggested that alterations in
      mucosal immune responses leading to appendicitis or resulting from appendectomy
      may negatively affect the pathogenic mechanisms of ulcerative colitis. Herein, we
      report a 45-year-old man who was diagnosed as severe ulcerative colitis 2 years
      ago. Colonoscopy revealed a feature of pancolitis. He has been treated with
      several courses of corticosteroids over 2 years. However, dosage of steroid was
      not tapered down because of the recurrence of symptoms. He was admitted with a
      diagnosis of acute appendicitis, and underwent appendectomy. Two months after the
      appendectomy, clinical symptoms and colonoscopic findings improved gradually. Two
      years after the appendectomy, the patient improved without the recurrences of
      symptoms, and is stably treated with sulfasalazine alone.

PMID- 16809956
TI  - [Steroid treatment of autoimmune pancreatitis].

PMID- 16809958
TI  - Trichomonas vaginalis and trichomoniasis in the Republic of Korea.
AB  - Vaginal trichomoniasis, caused by Trichomonas vaginalis, is the most common
      sexually transmitted disease. More than 170 million people worldwide are annually
      infected by this protozoan. In the Republic of Korea, 10.4% of women complaining
      of vaginal symptoms and signs were found to be infected with T. vaginalis.
      However, despite its high prevalence, the pathogenesis of T. vaginalis infection
      has not been clearly characterized although neutrophil infiltration is considered
      to be primarily responsible for the cytologic changes associated with this
      infection. We hypothesized that trichomonads in the vagina sometime after an
      acute infection secrete proteins like excretory-secretory product that have a
      chemotactic effect on neutrophils, and that these neutrophils are further
      stimulated by T. vaginalis to produce chemokines like IL-8 and GRO-alpha, which
      further promote neutrophil recruitment and chemotaxis. Thus, neutrophil
      accumulation is believed to maintain or aggravate inflammation. However, enhanced
      neutrophil apoptosis induced by live T. vaginalis could contribute to resolution
      of inflammation. Macrophages may constitute an important component of host
      defense against T. vaginalis infection. For example, mouse macrophages alone and
      those activated by lymphokines or nitric oxide are known to be involved in the
      extracellular killing of T. vaginalis. In the host, T. vaginalis uses a capping
      phenomenon to cleave host immunoglobulins with proteinases and thus escape from
      host immune responses. Recently, we developed a highly sensitive and specific
      diagnostic polymerase chain reaction (PCR) technique using primers based on a
      repetitive sequence cloned from T. vaginalis (TV-E650), and found that the method
      enables the detection of T. vaginalis at concentrations as low as 1 cell per PCR
      mixture.

PMID- 16809959
TI  - Genetic diversity of Acanthamoeba isolated from ocean sediments.
AB  - Genetic diversity of 18 Acanthamoeba isolates from ocean sediments was evaluated
      by comparing mitochondrial (mt) DNA RFLP, 18S rDNA sequences and by examining
      their cytopathic effects on human corneal epithelial cells versus reference
      strains. All isolates belonged to morphologic group II. Total of 16 restriction
      phenotypes of mtDNA from 18 isolates demonstrated the genetic diversity of
      Acanthamoeba in ocean sediments. Phylogenetic analysis using 18s rDNA sequences
      revealed that the 18 isolates were distinct from morphological groups I and III.
      Fifteen isolates showed close relatedness with 17 clinical isolates and A.
      castellanii Castellani and formed a lineage equivalent to T4 genotype of Byers
      group. Two reference strains from ocean sediment, A. hatchetti BH-2 and A.
      griffini S-7 clustered unequivocally with these 15 isolates. Diversity among
      isolates was also evident from their cytopathic effects on human corneal cells.
      This is the first time describing Acanthamoeba diversity in ocean sediments in
      Korea.

PMID- 16809960
TI  - Complement-mediated tail degradation of Neodiplostomum seoulense cercariae.
AB  - The furcocercus cercariae of Neodiplostomum seoulense (Digenea: Neodiplostomidae)
      penetrate the skins of tadpoles and shed their tails. The speculated mechanism of
      this tail loss was physical efforts required to produce a vigorous zigzag motion
      during skin penetration; no other mechanism has been proposed. We examined the
      relationship between the host serum and cercarial tail loss. Cercariae of N.
      seoulense were collected from experimentally infected Segmentina hemisphaerula,
      and lots of 300 cercariae were cultured in medium 199 contained several types of
      sera. Cercarial tail degradation was induced in all media, but all the cercariae
      cultured except those cultured in media containing fetal bovine serum (FBS) died
      within 48 hr. After 72 hr cultivation in media containing FBS, cercarial tail
      degradation was induced in 67.0%; in continuous cultivation 13.3% of larvae
      survived for 7 days. Tail degradation did not occur in the absence of serum and
      when serum was heat inactivated at 56 degrees Celsius for 30 min. The addition of
      20 mM ethylenediaminetetraacetic acid (EDTA) blocked cercarial tail degradation
      completely. Moreover, the addition of 20 mM MgCl2 restored tail degradation
      blocked by EDTA. These results suggest that the alternative complement pathway is
      related with the N. seoulense cercarial tail degradation induced by serum.

PMID- 16809961
TI  - Acaricidal effects of herb essential oils against Dermatophagoides farinae and D.
      pteronyssinus (Acari: Pyroglyphidae) and qualitative analysis of a herb Mentha
      pulegium(pennyroyal).
AB  - This experiment was undertaken to screen the acaricidal effects of herb essential
      oils (pennyroyal, ylang ylang, citronella, lemon grass, tea tree, and rosemary)
      at different doses (0.1, 0.05, 0.025, 0.0125, and 0.00625 microliter/cm(2)) and
      exposure times (5, 10, 20, 20, 30 and 60 min) on house dust mites Dermatophgoides
      farinae and D. pteronyssinus. The most effective acaricidal components of
      pennyroyal (Mentha pulegium) were analyzed using a gas chromatography-mass
      spectrometer (GC-MS). Of these essential oils, the most effective was pennyroyal,
      which is composed essentially of pulegone (> 99%), at a dose of 0.025
      microliter/cm(2), which at an exposure time of 5 min killed more than 98% of
      house dust mites. In the pennyroyal fumigation test, the closed method was more
      effective than the open method and maximum acaricidal effect was 100% at 0.025
      microliter/cm(2), 60 min. The results show that herb essential oils, in
      particular, pennyroyal was proved to have potent acaricidal activity.

PMID- 16809962
TI  - Peripheral gangrene in patients with severe falciparum malaria: report of 3
      cases.
AB  - Peripheral gangrene, characterized by distal ischemia of the extremities, is a
      rare complication in patients with falciparum malaria. Patients with this
      complication have generally undergone early amputation of the affected areas. In
      this report, we describe 3 adult Thai patients presented at the Hospital for
      Tropical Diseases, Bangkok, with high grade of fever ranged 6-9 days, jaundice,
      acute renal failure, respiratory failure, alteration of consciousness and shock.
      Two patients had gangrene developed at the lower extremities on day 1 of
      hospitalization and 1 patient had gangrene developed on day 3. Blood smears
      revealed hyperparasitemia with Plasmodium falciparum. These patients were
      diagnosed as having severe malaria with peripheral gangrene. The resolution of
      gangrene was successfully achieved by treatment with artesunate and conservative
      treatment in 2 of 3 cases.

PMID- 16809963
TI  - Three clinical cases of cutaneous larva migrans.
AB  - Three cases of cutaneous larva migrans (CLM) were diagnosed in a returnee from a
      trip to Thailand and in 2 domestic farmers during July and September, 2003. The
      linear and serpiginous skin lesions on the lower extremities were presented in
      all 3 cases. Routine laboratory findings were normal. In the imported case, a 650
      x 30 micrometer sized filariform nematode larva, presumably a species of
      hookworm, was detected in the lesion. All cases were treated with 400 mg
      albendazole once daily for 3-5 days, and their skin lesions gradually improved.
      In the present study, a causative agent of CLM was isolated for the first time in
      the Republic of Korea. Moreover, we speculate that CLM is prevalent in farmers
      who are in frequent contact with soil in the Republic of Korea.

PMID- 16809965
TI  - A case of histologically diagnosed tick infestation on the scalp of a Korean
      child.
AB  - A scalp mass surgically excised from a 4-year-old Korean boy was identified as a
      tick through histological observations. In sections of the mass, characteristic
      features of a tick, including its gross contour, cuticular structures, well
      developed musculature and salivary glands, and the capitulum, were discovered. In
      particular, the capitulum is anteriorly protruded, which strongly suggests that
      the specimen be a hard tick of family Ixodidae. However, the present histological
      features were not enough to determine the genus and species of the tick, because
      information on sectional morphologies of different tick species is unavailable.
      This is a rare case of tick infestation on the scalp diagnosed in histological
      sections.

PMID- 16809964
TI  - A surgically confirmed case of breast sparganosis showing characteristic
      mammography and ultrasonography findings.
AB  - A case of breast sparganosis was confirmed by surgical excision of a worm
      (fragmented into 5 pieces) in a 59-year-old Korean woman suffering from a
      palpable mass in the left breast. Mammography and ultrasonography
      characteristically revealed the presence of several well-defined, isodense and
      hypoechoic tubular masses, in the upper quadrant of the left breast, each mass
      consisting of a continuous cord- or worm-like structure. During surgery, a long
      segment of an actively moving sparganum of Spirometra sp. and 4 small fragments
      of the same worm, giving a total length of 20.3 cm, were extracted from the upper
      outer quadrant of the left breast and the axillary region. The infection source
      remains unclear, because the patient denied ingesting any snake or frog meat or
      drinking untreated water.

PMID- 16809966
TI  - Susceptibility of experimental animals to reinfection with Clonorchis sinensis.
AB  - The present study observed the resistance to reinfection with Clonorchis sinensis
      in various experimental animals including mice, guinea pigs, rabbits, and dogs,
      as well as rats and hamsters. The resistance rates to reinfection in rats, mice,
      hamsters, guinea pigs, rabbits, and dogs were 79.7%, 58.0%, -12.6%, 54.8%, 62.6%,
      and 6.0%, respectively. Worms recovered from reinfected rats and mice were
      immature, and significantly smaller than those from the primarily infected (P <
      0.01), whereas those from other animals were fully matured to adults. These
      findings indicate that the protective response against reinfection with C.
      sinensis is prominent in rats and mice, and that they may be a good animal model
      to investigate the mechanism of resistance to reinfection with C. sinensis.

PMID- 16809967
TI  - Feminization and reduction of testicular weight in mouse sparganosis.
AB  - After infection of male mice with the plerocercoids (spargana) of Spirometra
      mansoni, serum levels of estrogen and testicular weight were analyzed by enzyme
      linked immunosorbent assay (ELISA) and weighing machine, respectively. The serum
      level of estrogen increased progressively in infected mice compared with normal
      controls, whereas the testicular weight of infected mice decreased significantly
      (P < 0.05). These results suggest that certain substances from spargana change
      the steroid hormone metabolisms in the host by unknown pathways, and chronic
      infection may contribute to change of the function of steroid hormone target
      organ, i.e., testis, in male mice.

PMID- 16809968
TI  - Intestinal protozoan infections and echinococcosis in the inhabitants of Dornod
      and Selenge, Mongolia (2003).
AB  - The status of intestinal parasitic infections and seroprevalence of cystic
      echinococcosis in the inhabitants in Dornod and Selenge, Mongolia, was observed
      with stool and serum samples from 165 and 683 residents from August 9 to August
      15, 2003. A total of 10 inhabitants (6.1%) were found to be infected with
      protozoan cysts or oocysts by stool examinations; 7, 1 and 2 cases with Entamoeba
      coli, Giardia lamblia and Cryptosporidium parvum, respectively. A total of 62
      people (9.1%) revealed significantly high levels of specific antibodies against
      Echinococcus granulosus by enzyme-linked immunosorbent assay (ELISA). The
      surveyed areas are rural areas and the sanitized tab water is not available.
      There is a possibility of endemic transmission of water-borne protozoan diseases
      in these areas. The clinical echinococcosis is needed to be searched from the
      seropositive inhabitants.

PMID- 16809969
TI  - Factor structure of Eating Disorders Inventory-2 in a Spanish sample.
AB  - OBJECTIVE: To present basic statistics and analyze factor structure of EDI-2 in
      an adolescent non-clinical sample from Spain. METHOD: An Exploratory Factor
      Analysis (EFA) was carried out with Principal Axis Factoring (PAF) and oblimin
      rotation, using raw scores. RESULTS: EFA presented a 21-factor structure with
      eigenvalues greater than 1. It was then forced into 11 and 5-factor solutions.
      DISCUSSION: The eleven-factor structure does not correspond with the 11 scales. A
      five-factor structure seems to be better suited than other factor solutions and
      presented higher reliability coefficients.

PMID- 16809970
TI  - Olanzapine use in adolescent anorexia nervosa.
AB  - Several case reports and open label trials describe olanzapine in the treatment
      of anorexia nervosa (AN). We report 5 adolescents with AN who received olanzapine
      in addition to psychotherapy for their eating disorder. Body mass index (BMI) of
      each case increased while on olanzapine. At doses of 5 mg per day and above,
      patients reported decreased anxiety around eating, improved sleep, and decreased
      rumination about food and body concerns. Morning sedation was the most commonly
      reported adverse effect. Olanzapine appeared to be useful in addition to
      psychotherapy for these adolescents. This report augments a limited literature on
      the treatment of this disorder, and an almost nonexistent literature specific to
      pharmacotherapy for adolescents with AN.

PMID- 16809971
TI  - Body esteem and eating behaviours in female physical education students.
AB  - Certain university majors appear to be at greater risk of body dissatisfaction
      and disordered eating. The present study sought to examine self esteem, body
      satisfaction, and disordered eating in a sample of year one and year three female
      physical education students, and to compare them to a matched sample of non
      physical education females. Year three, but not year one physical education
      females, reported greater rates of disorder eating, but lower global self esteem,
      than non-physical education females. Dissatisfaction with sexual attractiveness,
      physical condition, and weight, were significantly related to disordered eating
      behaviours. Further research needs to be conducted with university majors that
      place a high premium on physical form and ability.

PMID- 16809972
TI  - Sexual abuse, bulimic symptoms, depression and satisfaction in adult
      relationships.
AB  - This study explored the role of depression as a mediator between self-reported
      sexual abuse and bulimic symptoms. Secondly, the study examined whether there was
      an association between sexual abuse, bulimic symptoms, or depression and
      satisfaction in relationships and avoidance of sexual interactions. Women (n=297)
      who reported experiencing bulimic symptoms and/or depression and women who were
      not symptomatic completed measures on sexual abuse, bulimic symptoms, depression,
      satisfaction in partner relationships and avoidance of sexual interactions. A
      path model analysis indicated that there were direct relationships between sexual
      abuse and depression, depression and low satisfaction in relationships and
      avoidance of sexual interactions. Sexual abuse was not directly related to
      bulimic symptoms when depression was included in the model. Nor was sexual abuse
      directly related to relationship difficulties. The findings of this study support
      a model of non-specific pathways between sexual abuse and bulimic symptoms.

PMID- 16809973
TI  - Eating disorders and the Internet: cure and curse.
AB  - OBJECTIVE: The role of culture and the mass-media in relation to eating disorders
      (EDs) is widely acknowledged, and the Internet has become an important part of
      this over the last few years. The aim of this report is to suggest the general
      features and potential clinical implications of "pro-Ana" websites and those
      concerning the treatment of EDs. METHOD: We conducted a Google search using the
      key words "anorexia nervosa (AN) and treatment", "AN and psychotherapy", "AN and
      pharmacotherapy", and then "pro-anorexia", "pro-ana sites", "thinspiration" and
      "anorexicnation". RESULTS: The first group of queries gave respectively 546,000,
      212,000 and 39,100 results; the second 257,000, 18,600, 14,200 and 577. Forty
      seven of 100 randomly selected pro-ana websites were thoroughly visited.
      CONCLUSIONS: Internet websites may increase the accessibility of treatments but
      also strengthen some of the core psychopathological and symptomatological issues
      of AN, such as asceticism, competition, purging behaviours and obsession for
      control. Greater attention should be paid to the health policy of countries in
      which pro-ana websites flourish, and the clinical implications of the websites
      themselves.

PMID- 16809974
TI  - Using the glucagon test to predict hypoglycemia in anorexia nervosa.
AB  - BACKGROUND: Hypoglycemia is an important but uncommon complication of anorexia
      nervosa (AN) that usually occurs when refeeding begins. The response to an iv
      bolus of glucagon has been used to investigate hypoglycemia, but not in AN. There
      are no published standards in AN to screen for hypoglycemia, to treat
      hypoglycemia, or for the response of the fasting blood sugar to an intravenous
      bolus of glucagon. METHOD: We report the change in blood glucose that resulted
      from bolus iv injection of glucagon in a case series of 9 patients with AN who
      were suspected of having experienced hypoglycemia. Our standard protocol for the
      glucagon test in AN is measurement of blood sugar at baseline, 10 minutes, and 20
      minutes following a 1.0 mg iv bolus of glucagon in the fasting state. We take as
      normal any blood glucose measurement of 7.0 mmol/l or greater. RESULTS: Five of
      nine patients had abnormal tests. The body mass index (BMI) was not different in
      those who had normal compared to those who had abnormal tests. CONCLUSION: The
      glucagon test may be of use to predict the likelihood of developing hypoglycemia
      in AN. However, a larger study is required to define the normal response to the
      glucagon test in AN.

PMID- 16809975
TI  - Core beliefs, recalled parental rearing and eating psychopathology across
      different age groups.
AB  - This study explored and compared the patterns of core beliefs, recalled parental
      rearing behaviours and eating psychopathology in non-clinical females of
      different ages; university staff and university students. No differences were
      found between the two age groups except that younger women had higher Drive for
      Thinness scores. However, core beliefs were associated with eating attitudes and
      behaviours in younger women and with recalled parental rearing behaviours in
      older women. The results suggest that younger women tend to externalise their
      negative core beliefs in the form of disordered eating behaviour whereas older
      women appear to express their dysfunctional core beliefs in ways other than
      weight and shape-related issues. The possible mechanisms behind these findings
      require further investigation.

PMID- 16809976
TI  - Psychopathological features of patients with prolonged anorexia nervosa as
      assessed by the Minnesota Multiphasic Personality Inventory.
AB  - OBJECTIVE: The duration of illness is quite long in some anorexia nervosa (AN)
      patients. In the present study, we investigated the psychopathological features
      of patients with prolonged AN as assessed by the Minnesota Multiphasic
      Personality Inventory-1 (MMPI-1). METHODS: Fifty-five AN patients completed the
      MMPI-1 on admission to Kyushu University Hospital from 1999 to 2002. The patients
      were divided into three groups on the basis of their illness duration: a short
      term group, less than 5 years of illness duration (n=31); a middle-term group,
      from 5 to 10 years (n=14); and a prolonged group, 10 years or more (n=10).
      RESULTS: The prolonged group scored significantly higher on the MPPI-1 scales of
      hysteria (Hy), low back pain (Lb) and family conflict than the short-term group.
      DISCUSSION: AN patients whose illness duration was prolonged characteristically
      had more hysteria with family conflict. This should be considered in their
      treatment.

PMID- 16809977
TI  - The eating disturbed spectrum in relation with coping and interpersonal
      functioning.
AB  - Although much has been written with regards to the interpersonal functioning of
      eating-disordered women, research in the domain of eating disorders (ED) has
      still overlooked the complex relationships between stressful life events, coping
      styles, social and marital support while considering the ED spectrum. OBJECTIVE:
      This study evaluates to what extent stressful life events, coping styles, and
      social support represent useful concepts for differentiating between four groups
      of participants with varying severity of eating preoccupations and disturbances.
      METHOD: One hundred twenty-five participants were divided into four groups: 40
      women suffering from ED, 21 women in remission from an ED, 33 women with intense
      weight and shape preoccupations, and 31 women without eating preoccupations. Each
      participant completed the Eating Disorder Evaluation, as well as questionnaires
      concerning stressful life events, coping styles, social support, and couple
      satisfaction. RESULTS: There were significant differences between the groups in
      terms of negative impact of stressful events, social support, as well as task
      oriented and emotion-oriented coping styles. Significant differences were not
      found between the groups for couple satisfaction. CONCLUSION: It appears that
      accurate cognitive appraisal of stressful situations, adaptive coping styles and
      improvement of the social network represent interesting dimensions to include in
      prevention and treatment programs for ED. Moreover, for women in remission from
      an ED, an effective relapse prevention strategy could be to learn to make better
      use of their social network.

PMID- 16809978
TI  - Factors related to renal dysfunction in patients with anorexia nervosa.
AB  - OBJECTIVE: Anorexia nervosa (AN) patients were surveyed to determine which
      disease factors were related to AN influenced renal dysfunction. METHODS: Data
      were from forty-five AN patients hospitalized in our department between 1995 and
      2002. The patients were classified into three groups based on the type of
      anorexia: restricting (n=18), self-induced vomiting (n=13), and laxative abuse
      (n=14). Twenty-four hour-creatinine clearance (Ccr) was calculated within two
      weeks of hospitalization for comparison among the three groups. RESULTS: The Ccr
      level of the laxative abuse group was significantly lower than that of the
      restricting group (65.8+/-31.4 ml/min vs restricting type: 104+/-23.3 ml/min,
      p=0.002). The laxative abuse group had a significantly longer duration of illness
      than the restricting group (p<0.0001). Multiple regression analysis revealed the
      duration of illness to be a risk factor for renal function deterioration in AN
      patients (r=0.580, p<0.001). DISCUSSION: Renal function should be carefully
      followed during the treatment of AN patients with a long duration of illness,
      especially those with long-term laxative abuse.

PMID- 16809979
TI  - A group parent-training program: a novel approach for eating disorder management.
AB  - OBJECTIVE: To describe the rationale, development, and preliminary acceptability
      of a Group Parent Training Program (GPT) as an alternative approach for the
      treatment of adolescent eating disorders. METHOD: Sixteen families participated
      in a 16-session group treatment. After four months, parents were administered a
      treatment satisfaction questionnaire. RESULTS: Parent response to the
      intervention was positive. All parents indicated GPT was essential for the
      management of their child, improved general parenting skills, improved their own
      self-care, and decreased the burden they experienced as a result of managing
      their child's illness. DISCUSSION: Given the magnitude of task demands placed on
      a family for the management of adolescent eating disorders, there is the need for
      the development of effective intervention strategies that ease the stress of
      illness management for parents. Preliminary satisfaction data from GPT are
      promising and argue for a more systematic test of this intervention.

PMID- 16809980
TI  - Establishing a useful distinction between current and anticipated bodily shame in
      eating disorders.
AB  - Previous research has suggested a role for bodily shame in the development of
      bulimia. The purpose of the present study was to extend this research by
      exploring a temporal perspective on bodily shame and eating pathology.
      Specifically, we were interested in whether bodily shame associated with the
      possibility of future weight gain was important in determining eating disorder
      symptoms independently of any association with bodily shame associated with
      current body size. A brief questionnaire designed to measure bodily shame was
      developed for the purposes of this study and administered to four samples (total
      n=428) of eating disordered and non-eating disordered women who also completed a
      number of measures of eating pathology. Factor analysis of the bodily shame scale
      identified three sub-scales, two measuring feelings of bodily shame (one
      measuring shame associated with current body size and one measuring shame that is
      anticipated should the individual gain weight) and a third measuring the
      perceived unattractiveness of being overweight. Anticipated bodily shame made a
      significant additional contribution to predicting eating disorder symptoms over
      and above that made by current bodily shame. A focus on feelings of bodily shame
      as they are currently experienced may limit the usefulness of this construct in
      eating disorder research. Since shame can be both punishing and prohibitive,
      consideration of the anticipation of shame as a consequence of weight gain may be
      a useful addition to understanding eating disordered behaviours, particularly in
      relation to symptoms concerning the prevention of weight gain rather than just
      the achievement of weight loss.

PMID- 16809981
TI  - Prevalence and correlates of chronic dieting in a multi-ethnic U.S. community
      sample.
AB  - Despite the increasing rates of obesity in the U.S. and corresponding rise in
      weight-related concerns among men and women in all ethnic groups, most research
      in the U.S. has been conducted using white female samples. This study explored
      the prevalence and correlates of chronic dieting (high levels of dietary
      restraint) among a U.S. communitybased sample of Hispanic, Asian, Black, and
      White women and men (N=1257). Chronic dieting was more common among women than
      men, and less common among Asians than other ethnic groups. Across the total
      sample, dietary restraint was positively correlated with weight history,
      disordered eating attitudes, distorted body experiences, and depression, and was
      negatively correlated with self-esteem. Female chronic dieters showed the highest
      degree of disturbance; compared with female non-dieters (and male chronic
      dieters), they reported lower self-esteem, higher depression, and more disordered
      eating attitudes. As hypothesized, they also exhibited a higher degree of
      acculturation to Anglo-American society. Male chronic dieters had more disordered
      eating attitudes and experienced greater body distortion than male non-dieters.
      Interestingly, these results were not moderated by ethnicity. Although the
      prevalence of chronic dieting differs among ethnic groups living in the U.S., the
      psychological characteristics related to eating and weight appear similar for
      individuals who diet, irrespective of ethnicity.

PMID- 16809982
TI  - A pilot study on body image, attractiveness and body size in Gambians living in
      an urban community.
AB  - OBJECTIVE: We investigated the attitudinal and perceptual components of body
      image and its link with body mass index (BMI) in a sample of urban Gambians. We
      also looked at cross-cultural differences in body image and views on
      attractiveness between Gambians and Americans. METHODS: Four groups of 50
      subjects were assessed: men 14- 25y (YM); women 14-25y (YW); men 35-50y (OM);
      women 35-50y (OW). Socio-economic status, education, healthy lifestyle and
      western influences were investigated. Height and weight were measured. Body
      dissatisfaction was assessed with the body dissatisfaction scale of the Eating
      Disorder Inventory. Perceptions of body image and attractiveness were assessed
      using the Body Image Assessment for Obesity (BIA-O) and Figure Rating Scale
      (FRS). RESULTS: Different generations of Gambians had very different perceptions
      and attitudes towards obesity. Current body size was realistically perceived and
      largely well tolerated. Older women had a higher body discrepancy (current minus
      ideal body size) than other groups (p<0.001). Regression analysis showed they
      were not worried about their body size until they were overweight (BMI=27.8
      kg/m2), whilst OM, YM and YW started to be concerned at a BMI respectively of
      22.9, 19.8 and 21.5 kg/m2. A cross-cultural comparison using published data on
      FRS showed that Gambians were more obesity tolerant than black and white
      Americans. DISCUSSION: The Gambia is a country in the early stage of demographic
      transitions but in urban areas there is an increase in obesity prevalence.
      Inherent tensions between the preservation of cultural values and traditional
      habits, and raising awareness of the risks of obesity, may limit health
      interventions to prevent weight gain.

PMID- 16809983
TI  - All roads do not lead to Rome.

PMID- 16809984
TI  - Postpneumonectomy pulmonary edema: good news, bad news.

PMID- 16809985
TI  - Automated anesthesia charge capture and submission: wave of the future, or bridge
      to nowhere?

PMID- 16809987
TI  - Lipid infusion resuscitation for local anesthetic toxicity: proof of clinical
      efficacy.

PMID- 16809988
TI  - Interscalene brachial plexus block: can the risk of entering the spinal canal be
      reduced? A study of needle angles in volunteers undergoing magnetic resonance
      imaging.
AB  - BACKGROUND: Spinal cord damage during interscalene brachial plexus block has been
      attributed to needle entry into the spinal canal. The purpose of this study was
      to identify the angles and depths of needle insertion that increase the
      likelihood of such an event, using the traditional classic interscalene approach
      and two more proximal entry points. METHOD: Magnetic resonance images of the neck
      from 10 healthy volunteers were used to obtain the three-dimensional spatial
      coordinates of three skin markers and the right-sided cervical nerves at the
      exiting neural foramina. The distance of the intervertebral foramina from the
      skin markers and the angles of the needle vector and the foramina were
      calculated. RESULTS: The distance from the skin to the intervertebral foramen may
      be as short as 2.5 cm with the classic approach. A caudal angulation greater than
      50 degrees seemed to eliminate the risk of needle entry through the foramen.
      CONCLUSION: With the classic approach to the interscalene block, there is a
      greater possibility of the needle passing through the intervertebral foramen if
      the needle is advanced too deeply. More proximal entry points and techniques that
      use a more steeply angled needle may reduce the risk of entry into the spinal
      space.

PMID- 16809989
TI  - Intraoperative tidal volume as a risk factor for respiratory failure after
      pneumonectomy.
AB  - BACKGROUND: Respiratory failure is a leading cause of postoperative morbidity and
      mortality in patients undergoing pneumonectomy. The authors hypothesized that
      intraoperative mechanical ventilation with large tidal volumes (VTs) would be
      associated with increased risk of postpneumonectomy respiratory failure. METHODS:
      Patients undergoing elective pneumonectomy at the authors' institution from
      January 1999 to January 2003 were studied. The authors collected data on
      demographics, relevant comorbidities, neoadjuvant therapy, pulmonary function
      tests, site and type of operation, duration of surgery, intraoperative ventilator
      settings, and intraoperative fluid administration. The primary outcome measure
      was postoperative respiratory failure, defined as the need for continuation of
      mechanical ventilation for greater than 48 h postoperatively or the need for
      reinstitution of mechanical ventilation after extubation. RESULTS: Of 170
      pneumonectomy patients who met inclusion criteria, 30 (18%) developed
      postoperative respiratory failure. Causes of postoperative respiratory failure
      were acute lung injury in 50% (n = 15), cardiogenic pulmonary edema in 17% (n =
      5), pneumonia in 23% (n = 7), bronchopleural fistula in 7% (n = 2), and pulmonary
      thromboembolism in 3% (n = 1). Patients who developed respiratory failure were
      ventilated with larger intraoperative VT than those who did not (median, 8.3 vs.
      6.7 ml/kg predicted body weight; P < 0.001). In a multivariate regression
      analysis, larger intraoperative VT (odds ratio, 1.56 for each ml/kg increase; 95%
      confidence interval, 1.12-2.23) was associated with development of postoperative
      respiratory failure. The interaction between larger VT and fluid administration
      was also statistically significant (odds ratio, 1.36; 95% confidence interval,
      1.05-1.97). CONCLUSION: Mechanical ventilation with large intraoperative VT is
      associated with increased risk of postpneumonectomy respiratory failure.

PMID- 16809990
TI  - Factors affecting perioperative transfusion decisions in patients with coronary
      artery disease undergoing coronary artery bypass surgery.
AB  - BACKGROUND: A high proportion of patients having cardiac bypass surgery receive
      erythrocyte transfusions. Decisions about when to transfuse patients having
      surgery for coronary artery disease may impact on erythrocyte utilization and
      patient morbidity and mortality. There are no published data about the factors
      that influence physicians' decisions to transfuse erythrocytes to these patients.
      The objectives of this study were to determine the hemoglobin concentration for
      transfusion and the factors that influence physicians' perioperative transfusion
      decisions for coronary artery bypass patients. METHODS: The authors conducted a
      cross-sectional study using pretested, self-administered, mailed questionnaires
      sent in 2004 to all cardiac surgeons and anesthesiologists in Canada who
      participate in coronary artery bypass surgery. The questionnaire included four
      intraoperative and four postoperative vignettes. Factors assessed included
      patient age, sex, cardiac index, and myocardial ischemia. RESULTS: The response
      rates were 70% (345 of 489) for the intraoperative and 61% (297 of 489) for the
      postoperative case scenarios. The mean hemoglobin concentrations for transfusion
      were 7.0 g/dl for the intraoperative case scenarios and 7.2 g/dl for the
      postoperative case scenarios. Older age, the presence of myocardial ischemia, and
      a low cardiac index were factors that increased the hemoglobin concentration for
      transfusion (P < 0.0001). Physicians ranked myocardial ischemia as the most
      significant factor affecting their transfusion decisions. CONCLUSIONS: Factors
      such as the presence of a low cardiac index, myocardial ischemia, and older age
      increase the hemoglobin concentrations at which physicians transfuse coronary
      bypass surgery patients. Future studies are required to elucidate whether
      transfusions based on these variables affect patient morbidity and mortality.

PMID- 16809991
TI  - Cerebral state index during propofol anesthesia: a comparison with the bispectral
      index and the A-line ARX index.
AB  - BACKGROUND: The objective of this study was to prospectively test the Cerebral
      State Index designed for measuring the depth of anesthesia. The Cerebral State
      Index is calculated using a fuzzy logic combination of four subparameters of the
      electroencephalographic signal. The performance of the Cerebral State Index was
      compared with that of the Bispectral Index and the A-Line ARX Index. METHODS:
      This study applied raw data from two previously published clinical protocols. The
      patients in protocol 1 were given a continuous propofol infusion, 300 ml/h, until
      80% of burst suppression occurred. In protocol 2, a stepwise increased target
      controlled infusion of propofol was administered to patients until loss of
      response to noxious stimuli while the Observer's Assessment of Alertness and
      Sedation was registered every 4 min. The Cerebral State Index was calculated off
      line from the recorded electroencephalographic data. The Spearman rank
      correlation coefficient between electronic indices and the effect site
      concentration of propofol was calculated along with the prediction probability of
      each index to predict the Observer's Assessment of Alertness and Sedation level.
      RESULTS: The Spearman rank correlation coefficients between the Cerebral State
      Index, Bispectral Index, and A-Line ARX Index and the propofol effect site
      concentration were -0.94, -0.89, and -0.82, respectively, in protocol 1, whereas
      the prediction probability values between the Cerebral State Index, Bispectral
      Index, and A-Line ARX Index and the Observer's Assessment of Alertness and
      Sedation score in protocol 2 were 0.92, 0.93, and 0.91, respectively. CONCLUSION:
      The Cerebral State Index detects well the graduated levels of propofol anesthesia
      when compared with the propofol effect site concentration and the Observer's
      Assessment of Alertness and Sedation score.

PMID- 16809992
TI  - Splanchnic oxygen consumption is impaired during severe acute normovolemic anemia
      in anesthetized humans.
AB  - BACKGROUND: In conscious humans, reduction in hemoglobin concentration to 5 g/dl
      did not produce inadequate systemic oxygenation. However, systemic measures of
      inadequate oxygenation may not be sufficiently sensitive to detect inadequate
      oxygenation in individual organs such as splanchnic organs. The authors tested
      the hypothesis that acute normovolemic anemia to hemoglobin less than 6.0 g/dl in
      anesthetized humans reduces splanchnic oxygen consumption because of diminished
      whole body oxygen delivery. METHODS: Elective spine (n = 12) and abdominal (n =
      7) surgery patients underwent acute normovolemic anemia to decrease the
      hemoglobin concentration close to 6.0 g/dl. The authors assessed the development
      of supply-dependent conditions in systemic and regional vascular beds by two
      primary measures before and after acute normovolemic anemia: oxygen consumption
      and surrogate biochemical markers of anaerobic metabolism, including plasma
      lactate, regional lactate kinetics, and ketone body ratio. RESULTS: When
      hemoglobin was reduced from 13.6 +/- 1.2 to 5.9 +/- 0.3 g/dl, oxygen supply
      dependency occurred in the splanchnic and preportal tissues but not at the
      systemic level. Regional supply dependency was accompanied by biochemical markers
      of anaerobic metabolism. CONCLUSIONS: In anesthetized humans, a reduction in
      hemoglobin to 5.9 g/dl by acute normovolemic anemia diminished splanchnic and
      preportal whole body oxygen delivery and impaired splanchnic and preportal oxygen
      consumption. This was accompanied by increased plasma levels of regional lactate
      and an increased beta-hydroxybutyrate-to-acetoacetate ratio. These findings
      suggest that the risk to the gastrointestinal tract during acute normovolemic
      anemia may be underestimated.

PMID- 16809993
TI  - Effect of propofol anesthesia and continuous positive airway pressure on upper
      airway size and configuration in infants.
AB  - BACKGROUND: Infants are prone to obstruction of the upper airway during general
      anesthesia. Continuous positive airway pressure (CPAP) is often used to prevent
      or treat anesthesia-induced airway obstruction. The authors studied the
      interaction of propofol anesthesia and CPAP on airway caliber in infants using
      magnetic resonance imaging. METHODS: Nine infants undergoing elective magnetic
      resonance imaging of the brain were studied. Head position was standardized. Spin
      echo magnetic resonance images of the airway were acquired at the level of the
      soft palate, base of the tongue, and tip of the epiglottis. Four sets of images
      were acquired in sequence: (1) during light propofol anesthesia at an infusion
      rate of 80 microg . kg(-1) . min(-1), (2) after increasing the depth of propofol
      anesthesia by administering a bolus dose (2.0 mg/kg) and increasing the infusion
      rate to 240 microg . kg(-1) . min(-1), (3) during continued infusion of 240
      microg . kg(-1). min propofol and application of 10 cm H2O CPAP, and (4) after
      removal of CPAP and continued infusion of 240 microg . kg(-1). min propofol.
      RESULTS: Increasing depth of propofol anesthesia decreased airway caliber at each
      anatomical level, predominantly due to anteroposterior narrowing. Application of
      CPAP completely reversed the propofol-induced decrease in airway caliber,
      primarily by increasing the transverse dimension. CONCLUSIONS: Airway narrowing
      with increasing depth of propofol anesthesia results predominantly from a
      reduction in anteroposterior dimension, whereas CPAP acts primarily to increase
      the transverse dimension. Although airway caliber during deep propofol anesthesia
      and application of CPAP was similar to that during light propofol anesthesia,
      there were significant configurational differences.

PMID- 16809994
TI  - Naloxone reversal of buprenorphine-induced respiratory depression.
AB  - BACKGROUND: The objective of this investigation was to examine the ability of the
      opioid antagonist naloxone to reverse respiratory depression produced by the mu
      opioid analgesic, buprenorphine, in healthy volunteers. The studies were designed
      in light of the claims that buprenorphine is relatively resistant to the effects
      of naloxone. METHODS: In a first attempt, the effect of an intravenous bolus dose
      of 0.8 mg naloxone was assessed on 0.2 mg buprenorphine-induced respiratory
      depression. Next, the effect of increasing naloxone doses (0.5-7 mg, given over
      30 min) on 0.2 mg buprenorphine-induced respiratory depression was tested.
      Subsequently, continuous naloxone infusions were applied to reverse respiratory
      depression from 0.2 and 0.4 mg buprenorphine. All doses are per 70 kg.
      Respiration was measured against a background of constant increased end-tidal
      carbon dioxide concentration. RESULTS: An intravenous naloxone dose of 0.8 mg had
      no effect on respiratory depression from buprenorphine. Increasing doses of
      naloxone given over 30 min produced full reversal of buprenorphine effect in the
      dose range of 2-4 mg naloxone. Further increasing the naloxone dose (doses of 5
      mg or greater) caused a decline in reversal activity. Naloxone bolus doses of 2-3
      mg, followed by a continuous infusion of 4 mg/h, caused full reversal within 40
      60 min of both 0.2 and 0.4 mg buprenorphine-induced respiratory depression.
      CONCLUSIONS: Reversal of buprenorphine effect is possible but depends on the
      buprenorphine dose and the correct naloxone dose window. Because respiratory
      depression from buprenorphine may outlast the effects of naloxone boluses or
      short infusions, a continuous infusion of naloxone may be required to maintain
      reversal of respiratory depression.

PMID- 16809995
TI  - Antagonistic actions of halothane and sevoflurane on spontaneous Ca2+ release in
      rat ventricular myocytes.
AB  - BACKGROUND: Halothane has been reported to sensitize Ca(2+) release from the
      sarcoplasmic reticulum (SR), which is thought to contribute to its initial
      positive inotropic effect. However, little is known about whether isoflurane or
      sevoflurane affect the SR Ca(2+) release process, which may contribute to the
      inotropic profile of these anesthetics. METHODS: Mild Ca(2+) overload was induced
      in isolated rat ventricular myocytes by increase of extracellular Ca(2+) to 2 mM.
      The resultant Ca(2+) transients due to spontaneous Ca(2+) release from the SR
      were detected optically (fura-2). Cells were exposed to 0.6 mM anesthetic for a
      period of 4 min, and the frequency and amplitude of spontaneous Ca(2+) transients
      were measured. RESULTS: Halothane caused a temporary threefold increase in
      frequency and decreased the amplitude (to 54% of control) of spontaneous Ca(2+)
      transients. Removal of halothane inhibited spontaneous Ca release before it
      returned to control. In contrast, sevoflurane initially inhibited frequency of
      Ca(2+) release (to 10% of control), whereas its removal induced a burst of
      spontaneous Ca(2+) release. Isoflurane had no significant effect on either
      frequency or amplitude of spontaneous Ca(2+) release on application or removal.
      Sevoflurane was able to ameliorate the effects of halothane on the frequency and
      amplitude of spontaneous Ca(2+) release both on application and wash-off.
      CONCLUSIONS: Application of halothane and removal of sevoflurane sensitize the SR
      Ca(2+) release process (and vice versa on removal). Sevoflurane reversed the
      effects of halothane, suggesting they may act at the same subcellular target on
      the SR.

PMID- 16809996
TI  - Flumazenil mimics whereas midazolam abolishes ischemic preconditioning in a
      rabbit heart model of ischemia-reperfusion.
AB  - BACKGROUND: The goal of the current study was to assess the effects of
      flumazenil, a benzodiazepine receptor antagonist, in limiting infarct size and in
      reducing hydroxyl free radical production. METHODS: After intravenous salicylate
      (100 mg/kg) administration, rabbits were subjected to 40 min of regional
      myocardial ischemia and 2 h of reperfusion. In one group, flumazenil (0.05 mg/kg)
      and, in another, midazolam (0.05 mg/kg) was administered 15 min before 40 min of
      ischemia. Ischemic preconditioning (IP) was elicited by 5 min of ischemia
      followed by 10 min of reperfusion (before the 40-min ischemia period). In two
      other groups, midazolam was added to flumazenil and IP. Infarct size was
      determined using triphenyl tetrazolium chloride staining. The authors quantified
      the hydroxyl-mediated conversion of salicylate to its 2,3- and 2,5
      dihydroxybenzoate derivatives during reperfusion by high-performance liquid
      chromatography coupled with electrochemical detection. Results are expressed as
      mean +/- SEM. RESULTS: Flumazenil, like IP, significantly decreased infarct size
      (23 +/- 4 and 22 +/- 5%, respectively, vs. 57 +/- 6% in control group; P < 0.01).
      Midazolam inhibited the effects of flumazenil and IP. Flumazenil and IP
      significantly limited the increase in the normalized concentrations of 2,3- and
      2,5-dihydroxybenzoic acids. With midazolam, however, the increase was comparable
      to that of the control group. 5-Hydroxydecanoate, a selective mitochondrial
      adenosine triphosphate-sensitive K channel blocker, given with flumazenil,
      abolished the protection obtained with the latter. CONCLUSIONS: Flumazenil mimics
      preconditioning to decrease infarct size and hydroxyl radical production during
      reperfusion. Midazolam, however, abolishes these effects. Blockade of
      benzodiazepine receptors is upstream to the mitochondrial adenosine triphosphate
      sensitive K channels in the preconditioning cascade.

PMID- 16809997
TI  - Noninvasive, automated and continuous cardiac output monitoring by pulmonary
      capnodynamics: breath-by-breath comparison with ultrasonic flow probe.
AB  - BACKGROUND: Cardiac output monitoring is most important where cardiovascular
      stability is potentially threatened, such as during major surgery and in
      critically ill patients. However, continuous monitoring of cardiac output is
      still not performed routinely during anesthesia and critical care, because of
      invasiveness, expense, and inaccuracy of available technologies. METHODS: A
      technique termed the capnodynamic method was tested for breath-to-breath
      measurement of pulmonary blood flow from lung carbon dioxide mass balance, using
      measured carbon dioxide elimination and end-tidal concentration. A prototype
      measurement system was constructed for a feasibility study in six anesthetized
      sheep. Large and rapid fluctuations in cardiac output were generated by repeated
      dobutamine and esmolol challenge. Measurements were compared with an indwelling
      ultrasonic flow probe placed on the ascending aorta or pulmonary artery. RESULTS:
      Cardiac output measured by the flow probe varied between zero and 8.67 l/min,
      with a mean of 3.50 l/min. Overall mean bias [SD of the difference] between the
      methods (capnodynamic - flow probe) was -0.25 [0.94] l/min, r = 0.79 (P < 0.001).
      During periods of stability in cardiac output of 5 min or more, mean bias was 
      0.20 [0.55] l/min. The method successfully indicated two cardiac arrest events,
      which were induced in one of the animals. CONCLUSIONS: The method satisfactorily
      tracked wide fluctuations in cardiac output in real time. The capnodynamic method
      may have potential for continuous noninvasive cardiac output monitoring in
      patients undergoing anesthesia for major surgery, and in critical care, on a
      routine basis.

PMID- 16809998
TI  - Selective gamma-aminobutyric acid type A receptor antagonism reverses isoflurane
      ischemic neuroprotection.
AB  - BACKGROUND: Isoflurane provides protection against severe forebrain ischemia in
      the rat. The authors hypothesized that this is attributable to interaction with
      the gamma-aminobutyric acid type A (GABAA) receptor resulting in altered time to
      onset of ischemic hippocampal depolarization. METHODS: Organotypic hippocampal
      slices were subjected to oxygen-glucose deprivation in the presence of isoflurane
      and combinations of GABAA (bicuculline) and GABAB (phaclofen) receptor
      antagonists. Cell death was measured. Rats were subjected to severe forebrain
      ischemia while anesthetized with fentanyl-nitrous oxide or 1.4% isoflurane. In
      the isoflurane group, rats also received intravenous bicuculline (0, 1, or 2
      mg/kg). Neurologic and histologic outcomes and time to depolarization were
      assessed. RESULTS: In slices, 2% isoflurane caused near-complete protection
      against oxygen-glucose deprivation. This was unaffected by coadministration of
      phaclofen but largely reversed by bicuculline. The GABAA agonist muscimol was
      also protective, having an effect equivalent to 1% isoflurane. In rats,
      isoflurane (0 mg bicuculline) improved neurologic and histologic outcome versus
      fentanyl-nitrous oxide (CA1 percentage of alive neurons: fentanyl-nitrous oxide,
      15 +/- 7; isoflurane, 61 +/- 24). The isoflurane effect was reversed in a dose
      dependent manner by bicuculline (CA1 percentage alive: 1 mg/kg, 44 +/- 22; 2
      mg/kg, 21 +/- 15). Time to depolarization was delayed with isoflurane versus
      fentanyl-nitrous oxide (137 vs. 80 s) but was not affected by bicuculline (149
      s). In contrast, postischemic time to repolarization was more rapid with fentanyl
      nitrous oxide or isoflurane plus bicuculline versus isoflurane alone.
      CONCLUSIONS: These studies are consistent with the hypothesis that the GABAA
      receptor serves as a major site of action for isoflurane neuroprotection both in
      vitro and in vivo. However, the mechanism by which this interaction confers in
      vivo protection cannot be attributed to effects on the duration of ischemic
      depolarization.

PMID- 16809999
TI  - Biologically variable ventilation improves oxygenation and respiratory mechanics
      during one-lung ventilation.
AB  - BACKGROUND: Hypoxemia is common during one-lung ventilation (OLV). Atelectasis
      contributes to the problem. Biologically variable ventilation (BVV), using
      microprocessors to reinstitute physiologic variability to respiratory rate and
      tidal volume, has been shown to be advantageous over conventional monotonous
      control mode ventilation (CMV) in improving oxygenation during the period of lung
      reinflation after OLV in an experimental model. Here, using a porcine model, the
      authors compared BVV with CMV during OLV to assess gas exchange and respiratory
      mechanics. METHODS: Eight pigs (25-30 kg) were studied in each of two groups.
      After induction of anesthesia-tidal volume 12 ml/kg with CMV and surgical
      intervention-tidal volume was reduced to 9 ml/kg. OLV was initiated with an
      endobronchial blocker, and the animals were randomly allocated to either continue
      CMV or switch to BVV for 90 min. After OLV, a recruitment maneuver was
      undertaken, and both lungs were ventilated for a further 60 min. At predetermined
      intervals, hemodynamics, respiratory gases (arterial, venous, and end-tidal
      samples) and mechanics (airway pressures, static and dynamic compliances) were
      measured. Derived indices (pulmonary vascular resistance, shunt fraction, and
      dead space ventilation) were calculated. RESULTS: By 15 min of OLV, arterial
      oxygen tension was greater in the BVV group (group x time interaction, P =
      0.003), and shunt fraction was lower with BVV from 30 to 90 min (group effect, P
      = 0.0004). From 60 to 90 min, arterial carbon dioxide tension was lower with BVV
      (group x time interaction, P = 0.0001) and dead space ventilation was less from
      60 to 90 min (group x time interaction, P = 0.0001). Static compliance was
      greater by 60 min of BVV and remained greater during return to ventilation of
      both lungs (group effect, P = 0.0001). CONCLUSIONS: In this model of OLV, BVV
      resulted in superior gas exchange and respiratory mechanics when compared with
      CMV. Improved static compliance persisted with restoration of two-lung
      ventilation.

PMID- 16810000
TI  - Distinct roles for sarcolemmal and mitochondrial adenosine triphosphate-sensitive
      potassium channels in isoflurane-induced protection against oxidative stress.
AB  - BACKGROUND: Cardiac preconditioning, including that induced by halogenated
      anesthetics, is an innate protective mechanism against ischemia-reperfusion
      injury. The adenosine triphosphate-sensitive potassium (K(ATP)) channels are
      considered essential in preconditioning mechanism. However, it is unclear whether
      K(ATP) channels are triggers initiating the preconditioning signaling, and/or
      effectors responsible for the cardioprotective memory and activated during
      ischemia-reperfusion. METHODS: Adult rat cardiomyocytes were exposed to oxidative
      stress with 200 microM H(2)O(2) and 100 microM FeSO4. Myocyte survival was
      determined based on morphologic characteristics and trypan blue exclusion. To
      induce preconditioning, the myocytes were pretreated with isoflurane. The
      involvement of sarcolemmal and mitochondrial K(ATP) channels was investigated
      using specific inhibitors HMR-1098 and 5-hydroxydecanoic acid. Data are expressed
      as mean +/- SD. RESULTS: Oxidative stress induced cell death in 47 +/- 14% of
      myocytes. Pretreatment with isoflurane attenuated this effect to 26 +/- 8%.
      Blockade of the sarcolemmal K(ATP) channels abolished the protection by
      isoflurane pretreatment when HMR-1098 was applied throughout the experiment (50
      +/- 21%) or only during oxidative stress (50 +/- 12%), but not when applied
      during isoflurane pretreatment (29 +/- 13%). Inhibition of the mitochondrial
      K(ATP) channels abolished cardioprotection irrespective of the timing of 5
      hydroxydecanoic acid application. Cell death was 42 +/- 23, 45 +/- 23, and 46 +/-
      22% when 5-hydroxydecanoic acid was applied throughout the experiment, only
      during isoflurane pretreatment, or only during oxidative stress, respectively.
      CONCLUSION: The authors conclude that both sarcolemmal and mitochondrial K(ATP)
      channels play essential and distinct roles in protection afforded by isoflurane.
      Sarcolemmal K(ATP) channel seems to act as an effector of preconditioning,
      whereas mitochondrial K(ATP) channel plays a dual role as a trigger and an
      effector.

PMID- 16810002
TI  - Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy.
AB  - BACKGROUND: Ketamine potentiates intravenous or epidural morphine analgesia. The
      authors hypothesized that very-low-dose ketamine infusion reduces acute and long
      term postthoracotomy pain. METHODS: Forty-nine patients scheduled to undergo open
      thoracotomy were randomly assigned to receive one of two anesthesia regimens:
      continuous epidural infusion of ropivacaine and morphine, along with intravenous
      infusion of ketamine (0.05 mg . kg(-1) . h(-1) [approximately 3 mg/h], ketamine
      group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was
      continued for 2 days after surgery, and infusion of ketamine or placebo was
      continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery.
      Patients were asked about their pain, abnormal sensation on the wound, and
      inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.
      RESULTS: The visual analog scale scores for pain at rest and on coughing 24 and
      48 h after thoracotomy were lower in the ketamine group than in the control group
      (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on
      coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P =
      0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating
      scale scores for baseline pain 1 and 3 months after thoracotomy were
      significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs.
      1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a
      higher number of control patients were taking pain medication (2 vs. 9; P =
      0.03). CONCLUSIONS: Very-low-dose ketamine (0.05 mg . kg(-1) . h(-1)) potentiated
      morphine-ropivacaine analgesia and reduced postthoracotomy pain.

PMID- 16810001
TI  - Midazolam inhibits proinflammatory mediators in the lipopolysaccharide-activated
      macrophage.
AB  - BACKGROUND: Midazolam, a benzodiazepine, has a hypnotic effect and is widely used
      as a sedative. The role of midazolam in activation of macrophages during sepsis
      is not known. The aim of this study was to evaluate the antiinflammatory actions
      of midazolam in cultured macrophages. METHODS: Using a macrophage cell line,
      RAW264.7 cells, the effect of midazolam on proinflammatory mediators and
      activation of mitogen-activated protein kinase was measured by Western blot.
      Nuclear factor-kappaB (NF-kappaB) activation and translocation of p65 subunit of
      NF-kappaB was measured using luciferase assay and immunocytochemistry. Superoxide
      production was measured by lucigenin chemiluminescence. RESULTS: Midazolam
      significantly inhibited lipopolysaccharide-induced up-regulation of both
      cyclooxygenase 2 and inducible nitric oxide synthase in a dose-dependent manner
      (approximately 3-30 microm). IkappaB-alpha degradation and NF-kappaB
      transcriptional activity induced by lipopolysaccharide were also suppressed by
      the midazolam. Nuclear translocation of the p65 subunit of NF-kappaB was
      inhibited by midazolam. Furthermore, midazolam suppressed phosphorylation of p38
      mitogen-activated protein kinase and also inhibited lipopolysaccharide-induced
      superoxide production in macrophages. CONCLUSIONS: These results suggest that
      midazolam has an antiinflammatory action by inhibiting inducible nitric oxide
      synthase and cyclooxygenase-2 expression, possibly through suppression of NF
      kappaB and p38 mitogen-activated protein kinase activation.

PMID- 16810003
TI  - Different brain activation patterns to pain and pain-related unpleasantness
      during the menstrual cycle.
AB  - BACKGROUND: The changes in the functional magnetic resonance imaging signal
      during anticipation, pain stimulation, and the poststimulation periods were
      investigated to determine whether changes in sex hormones affect brain activity.
      METHODS: Eighteen participants were examined twice, once in the follicular phase
      and once in the luteal phase. Half the participants were tested first during the
      follicular phase, and the other half were tested first in the luteal phase.
      RESULTS: The pain and unpleasantness ratings were significantly higher in the
      luteal phase than in the follicular. During the anticipation of pain, the
      prefrontal cortices were activated during the follicular phase, whereas the
      parahippocampal gyrus and amygdala were activated during the luteal phase. During
      the pain stimulation, putamen and cerebellum and precentral gyrus involving motor
      preparation and defense mechanism related to antinociceptive behavior were
      activated during the follicular phase, whereas the thalamus was activated during
      the luteal phase. During the poststimulation periods, the prefrontal cortices
      were activated during the follicular phase, whereas parahippocampal gyrus was
      activated during the luteal phase. The temporal pole was activated during the
      anticipation, pain stimulation, and poststimulation periods of the luteal phase.
      CONCLUSIONS: During surgical and medical procedures, requirements of anesthetic
      and analgesic and anxiolytic drugs may be reduced during the follicular phase and
      increased during the luteal phase. These results highlight the need to consider
      the effects of the sex hormones in women when designing clinical or neuroimaging
      studies or when treating patients for pain and pain-related unpleasantness.

PMID- 16810004
TI  - Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw
      inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines.
AB  - BACKGROUND: Local anesthetics exert antiinflammatory actions. To elucidate
      potential mechanisms, the authors examined effects of bupivacaine or
      tetrodotoxin, administered to rats by ipsilateral or contralateral sciatic
      blockade or systemically, on carrageenan-induced hind paw hyperalgesia, edema,
      and stimulated cytokine production in circulating blood cells. METHODS: Twelve
      groups of rats (n = 9-12) received injections in three sites: (1) right or left
      hind paw (carrageenan or saline), (2) left sciatic block, and (3) systemically
      (subcutaneously in the upper back). Sciatic and systemic injections were
      performed with epinephrine plus bupivacaine, tetrodotoxin, or saline; injections
      were repeated 6 h later. Fifteen hours later, hyperalgesia and/or sensory and
      motor block were assessed behaviorally, and paw edema was quantified by magnetic
      resonance imaging. Stimulated production of tumor necrosis factor alpha,
      interleukin 10, and interleukin 1beta in whole blood cultures was measured by
      enzyme-linked immunosorbent assay. RESULTS: Either ipsilateral or contralateral
      sciatic blocks using either bupivacaine or tetrodotoxin reduced carrageenan
      induced edema and hyperalgesia. Systemic bupivacaine and tetrodotoxin were
      ineffective in preventing edema and hyperalgesia. Bupivacaine was effective in
      suppressing systemic tumor necrosis factor alpha and interleukin 1beta by all
      three routes, whereas tetrodotoxin was ineffective by all three routes.
      CONCLUSION: Bupivacaine and tetrodotoxin, via a contralateral or ipsilateral
      sciatic block, attenuate local inflammatory edema and hyperalgesia induced by
      hind paw injection of carrageenan in rats. Mechanisms underlying contralateral
      effects of sciatic blockade remain unexplained. Bupivacaine inhibits carrageenan
      evoked systemic cytokine production by a mechanism not shared by tetrodotoxin;
      this action may involve tetrodotoxin-resistant sodium channels or a variety of
      non-sodium-channel targets.

PMID- 16810005
TI  - Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw
      inflammation in rats (Part 2): cytokines and p38 mitogen-activated protein
      kinases in dorsal root ganglia and spinal cord.
AB  - BACKGROUND: The authors previously showed that bupivacaine and tetrodotoxin via
      contralateral or ipsilateral sciatic block, but not systemically, attenuate local
      edema and hyperalgesia induced by carrageenan hind paw injection in rats.
      Bupivacaine, by all three routes, suppressed systemic cytokine activation,
      whereas tetrodotoxin was ineffective by all three routes. In the current study,
      the authors examined cytokine and p38 mitogen-activated protein kinase (MAPK)
      activation in lumbar dorsal root ganglia (DRGs) and spinal cord after carrageenan
      paw injections and sciatic blocks with either bupivacaine or tetrodotoxin.
      METHODS: Ten groups of rats (n = 3-5) received injections in the following sites:
      right or left hind paw or right forepaw (carrageenan or saline) and left sciatic
      block (with epinephrine plus bupivacaine, tetrodotoxin, or saline; repeated 6 h
      later). Fifteen hours later, tumor necrosis factor alpha, interleukin 1beta, p38
      MAPK, and phosphorylated p38 MAPK were measured by enzyme-linked immunosorbent
      assay in DRGs and in the spinal cord. RESULTS: Carrageenan-induced hind paw
      inflammation enhanced tumor necrosis factor-alpha and interleukin-1beta
      production in bilateral DRGs and spinal cord and enhanced p38 MAPK activation in
      bilateral DRGs. These pathways were not activated after forepaw injection of
      carrageenan, suggesting a segmental mechanism. Neither bupivacaine nor
      tetrodotoxin inhibited cytokine and p38 MAPK activation after carrageenan
      injection. CONCLUSION: Ipsilateral or contralateral sciatic blockade using either
      bupivacaine or tetrodotoxin does not inhibit carrageenan-induced activation of
      cytokines and p-38 MAPK in spinal cord and DRGs. Possible explanations may
      include incomplete degrees of conduction blockade or afferent signaling via
      saphenous nerves.

PMID- 16810006
TI  - Permeability of injured and intact peripheral nerves and dorsal root ganglia.
AB  - BACKGROUND: Nerve injury that produces behavioral changes of allodynia and
      hyperalgesia in animals is associated with electrophysiologic changes in dorsal
      root ganglion (DRG) cells. The introduction of drugs into the DRG or the
      peripheral nerve that alter calcium, sodium, or potassium channel activity may be
      of therapeutic benefit after nerve injury. For this reason, the authors sought to
      determine whether drugs that do not ordinarily cross the blood-nerve barrier will
      enter the DRG after intravenous or regional injection and to determine whether
      nerve injury alters drug access to DRGs or peripheral nerves. METHODS: Both
      intact and spinal nerve-ligated rats were injected with sodium fluorescein by
      intravenous, intrathecal, peri-DRG, perisciatic, and epidural routes. DRG,
      sciatic nerve, and spinal cord tissues were harvested and frozen, and histologic
      sections were analyzed quantitatively for tissue fluorescence. RESULTS: In both
      intact and nerve-injured animals, fluorescein accumulated in DRGs after
      intravenous, peri-DRG, and epidural injection. There was accumulation in the
      proximal portion of the ganglion after intrathecal injection. Minimal amounts of
      fluorescein were found in the sciatic nerve in intact animals after intravenous
      or perineural injection, but substantial amounts were found in some nerve
      fascicles in nerve-injured animals after both intravenous and perineural
      injection. There was almost no fluorescein found in the spinal cord except after
      intrathecal administration. CONCLUSIONS: In both intact and nerve-injured
      animals, fluorescein accumulates freely in the DRG after intravenous, epidural,
      or paravertebral injection. The sciatic nerve is relatively impermeable to
      fluorescein, but access by either systemic or regional injection is enhanced
      after nerve injury.

PMID- 16810007
TI  - Increased prostaglandin E2 release and activated Akt/beta-catenin signaling
      pathway occur after opioid withdrawal in rat spinal cord.
AB  - BACKGROUND: Prostaglandin E(2) is an important spinal modulator of nociception.
      However, the effects of chronic opioid administration and withdrawal on
      prostaglandin E(2) release and associated signaling pathways in the spinal cord
      are generally unknown. METHODS: This study sought to examine these effects using
      a spinal microdialysis technique in a model of chronic morphine administration
      and withdrawal in the rat. RESULTS: The authors found that spinal prostaglandin
      E(2) release was unaffected by chronic morphine treatment but was significantly
      increased during withdrawal. Recurrent withdrawal did not further enhance this
      release. The authors also found up-regulation of cyclooxygenase-2 expression and
      phosphorylation of protein kinase Akt at Ser-473 in response to opioid
      withdrawal. In addition, they demonstrated that beta-catenin, a transcription
      factor downstream of Akt, was induced during morphine withdrawal, particularly
      during recurrent withdrawal. CONCLUSIONS: These results suggest that opioid
      withdrawal activates signaling pathways associated with neuronal survival and
      transcriptional control, two processes implicated in neuronal development and
      synaptic plasticity.

PMID- 16810008
TI  - Painful peripheral nerve injury decreases calcium current in axotomized sensory
      neurons.
AB  - BACKGROUND: Reports of Ca(2+) current I(Ca) loss after injury to peripheral
      sensory neurons do not discriminate between axotomized and spared neurons. The
      spinal nerve ligation model separates axotomized from spared neurons innervating
      the same site. The authors hypothesized that I(Ca) loss is a result of neuronal
      injury, so they compared axotomized L5 dorsal root ganglion neurons to spared L4
      neurons, as well as neurons from rats undergoing skin incision alone. METHODS:
      After behavioral testing, dissociated neurons from L4 and L5 dorsal root ganglia
      were studied in both current and voltage patch clamp modes. The biophysical
      consequence of I(Ca) loss on the action potential was confirmed using selective
      I(Ca) antagonists. Data were grouped into small, medium, and large cells for
      comparison. RESULTS: Reduced I(Ca) was predominantly a consequence of axotomy (L5
      after spinal nerve ligation) and was most evident in small and medium neurons.
      ICa losses were associated with action potential prolongation in small and medium
      cells, whereas the amplitude and duration of after hyperpolarization was reduced
      in medium and large neurons. Blockade with Ca(2+) channel antagonists showed that
      action potential prolongation and after hyperpolarization diminution were alike,
      attributable to the loss of I(Ca). CONCLUSION: Axotomy is required for I(Ca)
      loss. I(Ca) loss correlated with changes in the biophysical properties of sensory
      neuron membranes during action potential generation, which were due to I(Ca) loss
      leading to decreased outward Ca(2+)-sensitive K currents. Taken together, these
      results suggest that neuropathic pain may be mediated, in part, by loss of I(Ca)
      and the cellular processes dependent on Ca(2+).

PMID- 16810009
TI  - Cerebrospinal fluid and spinal cord distribution of baclofen and bupivacaine
      during slow intrathecal infusion in pigs.
AB  - BACKGROUND: Increasing numbers of patients are receiving chronic intrathecal
      infusions of local anesthetics, baclofen, opioids, and other analgesics via
      implanted pumps. These infusions typically deliver drugs at rates measured in
      microliters per hour. However, to date, there have been no studies aimed at
      characterizing drug distribution within cerebrospinal fluid (CSF) and spinal cord
      during these slow infusion rates. Therefore, this study was designed to address
      this knowledge gap. METHODS: Anesthetized pigs were instrumented with eight
      intrathecal microdialysis probes placed at multiple points along the neuroaxis in
      both the anterior and posterior intrathecal space to permit continuous CSF
      sampling for measurement of bupivacaine and baclofen concentrations. Animals were
      divided into three groups and received bupivacaine and baclofen infusions at 20
      or 1,000 microl/h or as a 1,000-microl bolus over 5 min every hour. Drug
      administration continued for 8 h, at which time the animals were killed, and the
      spinal cord was removed and divided into 1-cm-long sections that were further
      divided into anterior and posterior portions for measurement of bupivacaine and
      baclofen concentrations. RESULTS: In all groups, drug concentration in CSF and
      spinal cord decreased rapidly as a function of distance from the site of
      administration, with most drug found within a few centimeters. In addition, there
      were significant anterior-posterior differences in both CSF and spinal cord drug
      concentrations. CONCLUSIONS: During slow intrathecal infusion, drug distribution
      in CSF and spinal cord is severely limited in all groups, although significantly
      more so in the 20-microl/h infusion group.

PMID- 16810010
TI  - Development of a module for point-of-care charge capture and submission using an
      anesthesia information management system.
AB  - BACKGROUND: The use of electronic charge vouchers in anesthesia practice is
      limited, and the effects on practice management are unreported. The authors
      hypothesized that the new billing technology would improve the effectiveness of
      the billing interface and enhance financial practice management measures.
      METHODS: A custom application was created to extract billing elements from the
      anesthesia information management system. The application incorporates business
      rules to determine whether individual cases have all required elements for a
      complete and compliant bill. The metrics of charge lag and days in accounts
      receivable were assessed before and after the implementation of the electronic
      charge voucher system. RESULTS: The average charge lag decreased by 7.3 days
      after full implementation. The total days in accounts receivable, controlling for
      fee schedule changes and credit balances, decreased by 10.1 days after
      implementation, representing a one-time revenue gain equivalent to 3.0% of total
      annual receipts. There are additional ongoing cost savings related to reduction
      of personnel and expenses related to paper charge voucher handling. CONCLUSIONS:
      Anesthesia information management systems yield financial and operational
      benefits by speeding up the revenue cycle and by reducing direct costs and
      compliance risks related to the billing and collection processes. The observed
      reductions in charge lag and days in accounts receivable may be of benefit in
      calculating the return on investment that is attributable to the adoption of
      anesthesia information management systems and electronic charge transmission.

PMID- 16810011
TI  - Molecular mechanisms transducing the anesthetic, analgesic, and organ-protective
      actions of xenon.
AB  - The anesthetic properties of xenon have been known for more than 50 yr, and the
      safety and efficacy of xenon inhalational anesthesia has been demonstrated in
      several recent clinical studies. In addition, xenon demonstrates many favorable
      pharmacodynamic and pharmacokinetic properties, which could be used in certain
      niche clinical settings such as cardiopulmonary bypass. This inert gas is capable
      of interacting with a variety of molecular targets, and some of them are also
      modulated in anesthesia-relevant brain regions. Besides these anesthetic and
      analgesic effects, xenon has been shown to exert substantial organoprotective
      properties, especially in the brain and the heart. Several experimental studies
      have demonstrated a reduction in cerebral and myocardial infarction after xenon
      application. Whether this translates to a clinical benefit must be determined
      because preservation of myocardial and cerebral function may outweigh the
      significant cost of xenon administration. Clinical trials to assess the impact of
      xenon in settings with a high probability of injury such as cardiopulmonary
      bypass and neonatal asphyxia should be designed and underpinned with
      investigation of the molecular targets that transduce these effects.

PMID- 16810012
TI  - Practice guidelines for perioperative blood transfusion and adjuvant therapies:
      an updated report by the American Society of Anesthesiologists Task Force on
      Perioperative Blood Transfusion and Adjuvant Therapies.

PMID- 16810013
TI  - The Mayo Clinic World War II short course and its effect on anesthesiology.

PMID- 16810014
TI  - Myocardial ischemia revisited.
AB  - Does perioperative myocardial ischemia lead to postoperative myocardial
      infarction? By Stephen Slogoff and Arthur S. Keats. Anesthesiology 1985; 62:107
      14. Reprinted with permission. To determine if a relationship exists between
      perioperative myocardial ischemia (ST segment depression greater than or equal to
      0.1 mV) and postoperative myocardial infarction (PMI), nonparticipating observers
      recorded all electrocardiographic, hemodynamic, and other events between arrival
      of patients in the operating room and onset of cardiopulmonary bypass during
      1,023 elective coronary artery bypass operations (CABG). The roles of
      preoperative patient characteristics, quality of the operation limited by disease
      as rated by the surgeon and duration of ischemic cardiac arrest as risk factors
      for PMI also were quantified. Electrocardiographic ischemia occurred in 36.9% of
      all patients, with almost half the episodes occurring before induction of
      anesthesia. PMI was almost three times as frequent in patients with ischemia
      (6.9% vs. 2.5%) and was independent of when ischemia occurred. Ischemia was
      related significantly to tachycardia but not hypertension nor hypotension and was
      frequent in the absence of any hemodynamic abnormalities. The anesthesiologist
      whose patients had the highest rate of tachycardia and ischemia had the highest
      rate of PMI. Although neither single nor multiple preoperative patient
      characteristics related to PMI, suboptimal quality of operation and prolonged
      ischemic cardiac arrest increased the likelihood of PMI independent of the
      occurrence of myocardial ischemia. The authors conclude that perioperative
      myocardial ischemia is common in patients undergoing CABG, occurs randomly as
      well as in response to hemodynamic abnormalities, and is one of three independent
      risk factors the authors identified as related to PMI. PMI is unrelated to
      preoperative patient characteristics such as ejection fraction and left main
      coronary artery disease, and its frequency will relate primarily to perioperative
      management rather than patient selection.

PMID- 16810015
TI  - Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed
      bupivacaine-related cardiac arrest.

PMID- 16810016
TI  - A case of severe diffuse venous thromboembolism associated with aprotinin and
      hypothermic circulatory arrest in a cardiac surgical patient with factor V
      Leiden.

PMID- 16810017
TI  - Dose inflation when using precurarization.

PMID- 16810018
TI  - Is the dose-related reduction in succinylcholine-induced myalgia due to
      cointervention?

PMID- 16810020
TI  - Anesthesia preoperative medicine clinic: beyond surgery cancellations.

PMID- 16810021
TI  - Effects of an anesthesia preoperative medicine clinic.

PMID- 16810023
TI  - A new method for detecting the proximal aortic arch and innominate artery by
      transesophageal echocardiography.

PMID- 16810024
TI  - An error associated with an epidural drug infusion pump.

PMID- 16810025
TI  - Methylene blue treatment for methemoglobinemia and subsequent dramatic bispectral
      index reduction.

PMID- 16810027
TI  - Myocardial ischemia during everyday life in patients with arterial hypertension:
      prevalence, risk factors, triggering mechanism and circadian variability.
AB  - INTRODUCTION: The objective of the present study was to investigate the
      prevalence, the risk factors, the hemodynamic triggering mechanisms, the
      circadian variability of ST segment depression (ST depression) and the effect of
      day and night fall in blood pressure on the prevalence of ST depression in
      hypertensive patients. MATERIALS AND METHODS: In a multicentric study in Germany,
      1,244 CardioTens registrations (combined 24-h ambulatory blood pressure
      measurement/electrocardiography with ST segment triggering; Meditech, Budapest,
      Hungary) from patients with arterial hypertension were consecutively monitored
      and evaluated centrally at the University of Bonn. Inclusion criterion was
      treated or untreated arterial hypertension. The ST segment was measured in
      accordance with the "1 : 1 : 1 rule" (horizontal or descending ST depression by 1
      mm, 1 min duration, 1 min interval from the previous episode). RESULTS: ST
      segment depression was observed in 250 (20.1%) patients; 90.3% of the transient
      ST-segment depression was silent (without angina pectoris). Ambulatory 24-h blood
      pressure measurement, but not office-based blood pressure measurement, was
      predictive for the occurrence of ST-segment depression. Risk factors for ST
      segment depression were the Sokolow index > or =3.5 mV, smoking status, severity
      of coronary heart disease, use of diuretics, reduced left ventricular function,
      pulse pressure > or =60 mmHg and increase of double product (1,000 mmHg/min). A
      significant rise of the systolic/diastolic blood pressure (+8+ or -18/+7+ or -10
      mmHg), of the heart rate (+12+ or -13/min) and of the double product (+2,471+ or 
      2,517 mmHg/min) was found during the transient ST depression as compared with the
      corresponding 24-h ambulatory blood pressure measurement mean values (P<0.0001
      for all parameters specified). In most intermittent ST depressions, a rise of the
      double product was seen (n=789 episodes), and in the remaining 239 ST
      depressions, a fall of the double product was observed. ST depressions with fall
      of the double product showed a circadian distribution with a peak in the late
      evening. ST depression accompanied by a rise in double product showed two peaks
      (one in the early morning and one in the late evening). The prevalence of ST
      depression was significantly higher (28.6%) in extreme dippers than in dippers
      (18.2%), risers (21.8%) and non-dippers (19.6%). CONCLUSIONS: ST depressions have
      a high prevalence of 20.1% in hypertensive patients. Clinical predictors for the
      occurrence of ST-segment depression were classical risk factors and cardiac
      target organ damage. Office-based blood pressure measurement was not a useful
      measuring tool for forecasting the likelihood of ST-segment depression. ST
      depressions were triggered inter alia by variations of blood pressure and the
      heart rate. The circadian variability of the ST depressions is crucially affected
      by the pressure double product characteristics on which the ST depression is
      based.

PMID- 16810028
TI  - Postexercise hypotension induced by low-intensity resistance exercise in
      hypertensive women receiving captopril.
AB  - OBJECTIVE: The present study investigated the effect of a single bout of low
      intensity resistance exercise on recovery blood pressure in hypertensive women
      receiving captopril. METHODS: Twelve essential hypertensive women, who were
      receiving captopril, underwent two experimental sessions: control (C - 40 min of
      seated rest) and low-intensity resistance exercise (E - six resistance exercises,
      three sets, 20 repetitions, 40% of one repetition maximum). Clinic blood pressure
      was measured in the laboratory, before and for 120 min after exercise or rest.
      Moreover, ambulatory blood pressure was also measured for 21 h after exercise or
      rest. RESULTS: Clinic blood pressures decreased significantly after exercise
      (systolic blood pressure =-12+ or -3 mmHg and diastolic blood pressure =-6+ or -2
      mmHg, P<0.05), but not after rest. Mean awake blood pressures (systolic: C=132+
      or -5 mmHg vs. E=125+ or -4 mmHg and diastolic: C=83+ or -3 mmHg vs. E=78+ or -2
      mmHg, P<0.05) were significantly lower in the E than in the C session, while 21-h
      (systolic blood pressures: C=128+ or -5 mmHg vs. E=123+ or -4 mmHg; and diastolic
      blood pressures: C=80+ or -3 mmHg vs. E=76+ or -2 mmHg) and asleep (systolic
      blood pressures: C=120+ or -7 mmHg vs. E=118+ or -5 mmHg; and diastolic blood
      pressures: C=73+ or -4 mmHg vs. E=71+ or -3 mmHg) blood pressures did not differ
      between the experimental sessions. Moreover, there was a positive correlation
      between blood pressure measured in the C session and blood pressure reduction
      observed in the E session, showing that blood pressure decrease was greater when
      blood pressure level was higher. CONCLUSION: In hypertensive women receiving
      captopril, a single bout of low-intensity resistance exercise reduces blood
      pressure. This reduction persists for 10 h, during the awake period, while
      patients were engaged in their daily living activities. It was greater in
      patients with higher ambulatory blood pressure.

PMID- 16810029
TI  - Aortic elastic properties and left ventricular diastolic function in white-coat
      hypertensive individuals.
AB  - OBJECTIVES: Although white-coat hypertension may be present in 25% or more of
      hypertensive individuals, its prognostic significance and predisposition to end
      organ damage is unknown. To evaluate whether white-coat hypertension is
      associated with end organ damage, we compared prognostically relevant measures of
      target-organ damage among 35 individuals with white-coat hypertension and age and
      sex-matched groups of sustained hypertension and normotensive individuals
      classified by clinical and 24-h ambulatory blood pressures. METHODS: We evaluated
      left ventricular diastolic function and aortic elastic properties of 35
      individuals with white-coat hypertension, 50 patients with sustained
      hypertension, and 35 normotensive healthy volunteers using transthoracic Doppler
      echocardiography. None of the study participants with sustained hypertension and
      white-coat hypertension, who were newly diagnosed and never treated, had any
      systemic disease or coronary risk factor except hypertension. RESULTS: Age, sex,
      and body mass indexes were similar among the three groups. Left ventricular
      diastolic function was more significantly impaired in the sustained hypertension
      and white-coat hypertension groups than in the control group, but it was not
      significantly different between the white-coat hypertension and sustained
      hypertension groups. Aortic distensibility was significantly lower, and aortic
      stiffness index was significantly higher in the sustained hypertension group than
      in the white-coat hypertension and control groups. Furthermore, aortic elastic
      properties were slightly impaired in the white-coat hypertension group compared
      with those in the control group. We also found a significant correlation between
      aortic elastic properties and left ventricular diastolic function. CONCLUSIONS:
      White-coat hypertension may alter left ventricular diastolic function and aortic
      elastic properties. These alterations, however, might not be as remarkable as
      those caused by sustained hypertension. In this respect, individuals with white
      coat hypertension are not at such a risk for end organ damage as patients with
      sustained hypertension.

PMID- 16810030
TI  - Blood pressure in acute ischemic stroke and mortality: a study with noninvasive
      blood pressure monitoring.
AB  - BACKGROUND: In acute ischemic stroke, a transient elevation of blood pressure is
      common; its significance and its relationship with the neurological outcome are
      still unclear. METHODS: In 71 consecutive patients with acute ischemic stroke,
      aged 25-94 years, admitted to our unit, we investigated the relationships between
      the blood pressure variation during the first 24 h and mortality at 3 months
      (study endpoint). Neurological status was assessed with the National Institutes
      of Health Stroke Scale. Blood pressure was measured with bedside noninvasive
      blood pressure monitoring every 15 min. The mean of four measurements at the
      emergency department and the mean of 12 measures (during a 3-h interval) at 12
      and at 24 h after stroke onset were considered for analysis. Antihypertensive
      treatment was given in accordance with the Recommendations for Stroke Management
      of European Stroke Initiative. RESULTS: In the whole series, 21% were
      atherothrombotic, 32% cardioembolic, 34% lacunar, and 13% of unknown or other
      cause. Blood pressure was 160+ or -3/86+ or -2 mmHg at the emergency department,
      148+ or -3/82+ or -2 mmHg at 12 h, and 147+ or -3/81+ or -2 mmHg at 24 h
      (P<0.05). Four patients (11%) of those in whom mean blood pressure decreased >5
      mmHg, and 12 (33%) of the others, in whom mean blood pressure decreased < or =5
      mmHg or did not decrease, reached the endpoint (P<0.05). According to the
      multivariate Cox model, NIHSS score at the emergency department (95% confidence
      interval: 1.025-1.238, P=0.013) and age (95% confidence interval: 1.007-1.259,
      P=0.038) were predictors of reaching the endpoint, whereas mean blood pressure
      reduction 24 h after stroke onset had a protective effect (95% confidence
      interval: 0.845-0.995, P=0.038). Diabetes, mean blood pressure at the emergency
      department and the need for antihypertensive therapy did not correlate with the
      outcome. CONCLUSIONS: Noninvasive blood pressure monitoring during the first 24 h
      of acute ischemic stroke may be useful in the prognostic stratification by
      showing moderate blood pressure decrease, either spontaneous or drug induced,
      which is associated with a favorable prognosis at 3 months.

PMID- 16810031
TI  - Home blood pressure in poorly controlled hypertension: relationship with
      ambulatory blood pressure and organ damage.
AB  - OBJECTIVES: (1) To assess whether home blood pressure measurement is a reliable
      alternative to ambulatory blood pressure monitoring for the evaluation of treated
      patients with inadequate blood pressure control at the clinic; and (2) to
      evaluate the relationship between home blood pressure and several target-organ
      damage markers. BASIC METHODS: A cross-sectional study was performed in 225
      treated hypertensive patients with persistently high blood pressure values at the
      clinic (systolic blood pressure 140 mmHg and/or diastolic blood pressure 90
      mmHg). All study participants underwent clinic blood pressure measurement, 24-h
      ambulatory blood pressure and home blood pressure monitoring. A subgroup of
      patients underwent the following procedures: carotid echography (n=74),
      microalbuminuria determination (n=88) and echocardiography (n=43). We defined out
      of-clinic normotension as an average ambulatory or home blood pressure less than
      135 mmHg (systolic) and 85 mmHg (diastolic). MAIN RESULTS: The sensitivity,
      specificity and positive and negative predictive values of the home blood
      pressure method for predicting out-of-clinic normotension (with the ambulatory
      method used as reference), expressed as percentages, were 50, 87, 64 and 79%,
      respectively. Systolic home blood pressure correlated significantly with left
      ventricular mass (r=0.33, P<0.05) and microalbuminuria (r=0.24, P<0.05). Similar
      correlation coefficients were found for systolic ambulatory blood pressure
      (r=0.32, P<0.05 and r=0.24, P<0.05, respectively). Clinic blood pressure did not
      correlate with either left ventricular mass or microalbuminuria (r=0.19, P=0.09
      and r=0.19, P=0.24, respectively). Diastolic home blood pressure, but not
      ambulatory blood pressure, correlated negatively with mean carotid intima-media
      thickness (r=-0.27, P<0.05). CONCLUSION: Our results suggest that, in patients
      with poorly controlled hypertension at the clinic, home blood pressure represents
      a complementary test rather than an alternative to ambulatory blood pressure, and
      correlates with several target-organ damage markers.

PMID- 16810032
TI  - Clinical use of indices determined non-invasively from the radial and carotid
      pressure waveforms.
AB  - OBJECTIVE: To evaluate the clinical use of radial and carotid artery applanation
      tonometry as an independent supplement to cuff sphygmomanometry. METHODS: In 44
      patients, radial and carotid tonometric pressure recordings were taken at short
      intervals apart by two persons who had prolonged experience with both.
      Comparisons were made between directly recorded radial and carotid waveforms and
      between aortic waves synthesized from both, using SphygmoCor. Focus was on
      waveform features: time intervals between wavefoot and incisura, denoting
      ejection duration, between wavefoot and first systolic peak or shoulder T1, and
      augmentation index - the rise in pressure from this point to systolic peak
      divided by pulse pressure. RESULTS: No patient had discomfort with radial
      tonometry, whereas many found carotid tonometry uncomfortable. Beat-to-beat
      variability was lower for the radial than carotid site. The device's operator
      "quality index" was achieved for 78% of radial waveforms but just 20% of carotid
      waveforms (P<0.05). Interobserver variability was lower for all indices derived
      from radial, cf. carotid, waveforms. For the two observers combined, there was no
      difference between aortic indices determined from carotid and radial sites except
      for T1 (radial-derived 117+ or -17 ms, cf. carotid-derived 103+ or -17 ms,
      P<0.05), but this did not influence the value of augmentation index (radial
      derived 26+ or -13%, cf. carotid-derived 28+ or -14%, P=NS). CONCLUSION: The
      present study conforms with most published results, and indicates superiority of
      radial to carotid tonometry in clinical practice.

PMID- 16810033
TI  - Validation of the A&D UA-705 device for self-measurement of blood pressure
      according to the British Hypertension Society protocol.
AB  - OBJECTIVES: We tested the accuracy of the UA-705 blood pressure semi-automatic
      monitor. METHODS: Device evaluation was performed according to the modified
      British Hypertension Society protocol released in 1993. Eighty-five patients with
      characteristics outlined in the British Hypertension Society protocol were
      recruited among those attending our out-patient clinic. Sequential readings were
      taken for the main validation test. Outcome was classified according to the
      British Hypertension Society criteria, which are based on four zones of accuracy
      differing from the mercury standard by 5, 10 and 15 mmHg, or more. RESULTS: The
      mean blood pressure difference (+ or -1 SD) between device and observers was 0.4
      mmHg (SD 7.7) for systolic blood pressure and 0.3 mmHg (SD 8.2) for diastolic
      blood pressure. Overall, 96% (observer 1) and 95% (observer 2) of readings
      between device and observers differed by 15 mmHg or less for both systolic and
      diastolic blood pressure. The device achieved a grade A for both systolic and
      diastolic blood pressure. CONCLUSIONS: This study shows that the A&D UA-705
      device satisfies the British Hypertension Society standard for accuracy by
      achieving a grade A for both systolic and diastolic blood pressure.

PMID- 16810034
TI  - Validation of the Omron 705 IT oscillometric device for home blood pressure
      measurement in children and adolescents: the Arsakion School Study.
AB  - BACKGROUND: Limited evidence exists on the accuracy of oscillometric devices for
      blood pressure measurement in children. This study validated the Omron 705 IT
      monitor (Omron Healthcare Europe BV, Hoofddorp, The Netherlands) in normotensive
      children and adolescents. METHODS: Simultaneous blood pressure measurements were
      taken by two observers (connected mercury sphygmomanometers) four times,
      sequentially with three measurements by using the tested device. Absolute device
      observer blood pressure differences were classified into three zones (within 5,
      10 and 15 mmHg) and assessed using the European Society of Hypertension
      International Protocol criteria. The number of readings with a difference within
      5 mmHg was calculated for each individual. The American Association for the
      Advancement of Medical Instrumentation criterion (mean difference+ or -SD <5+ or 
      8 mmHg) was also applied. RESULTS: A total of 197 study participants (591
      readings) were included (99 boys, mean age+ or -SD 10.6+ or -2.4 years (range 6
      16 years). The device produced 378 (64%), 532 (90%) and 579 (98%) measurements
      within 5, 10 and 15 mmHg, respectively, for systolic blood pressure, and 415
      (70%), 525 (89%) and 577 (98%) measurements, respectively, for diastolic blood
      pressure. In all, 136 study participants (69%) had at least two systolic blood
      pressure differences within 5 mmHg and 16 (8%) had no differences within 5 mmHg
      (for diastolic blood pressure 147 (75%) and nine (5%) participants,
      respectively). Mean systolic blood pressure difference was 4.0+ or -4.8 mmHg and
      diastolic blood pressure -2.1+ or -5.9 mmHg and was <5+ or -8 mmHg in quartiles
      of participants divided by age, height, body mass index, arm circumference, blood
      pressure or pulse rate. CONCLUSIONS: The Omron 705 IT appears to be an accurate
      device for blood pressure measurement in normotensive children and adolescents.

PMID- 16810037
TI  - Management of perioperative nutrition support.
AB  - PURPOSE OF REVIEW: Perioperative nutrition has been extensively studied, but
      numerous questions remain unanswered. This review focuses on new developments in
      nutrient delivery in the immediate perioperative period. Issues specifically
      addressed include which patients are most likely to benefit from perioperative
      nutritional supplementation, and the optimal route, timing, and quantity of
      nutrient delivery. RECENT FINDINGS: Visceral proteins, particularly albumin, play
      an important role in nutritional and perioperative risk assessment. Although the
      recommendation to use the enteral route for delivery of nutrition whenever
      possible is clear, the cautious introduction of enteral feeds in the labile group
      of patients with circulatory failure is essential. Preoperative use of immune
      modulating enteral formulas, preoperative carbohydrate loading, and the concept
      of early enteral feeding are important developments. Supplementary arginine,
      glutamine, and omega-3 fats play a potential role in nutritional management, as
      does 'permissive' hypocaloric feeding. SUMMARY: The particulars of nutritional
      support for perioperative and critically ill patients remain controversial.
      Recent studies addressing specific issues in this diverse discipline perhaps
      raise more questions than are answered. However, each new contribution to the
      literature brings us closer to an understanding of optimal nutritional management
      in the metabolically stressed patient.

PMID- 16810038
TI  - Use of novel prokinetic agents to facilitate return of gastrointestinal motility
      in adult critically ill patients.
AB  - PURPOSE OF REVIEW: Intolerance of enteral feeding due to impaired
      gastrointestinal motility is common in critically ill patients. Strategies to
      prevent or treat gastrointestinal hypomotility include the use of prokinetic
      agents. Many currently employed prokinetic agents are associated with serious
      adverse drug reactions. The novel prokinetic agents - alvimopan, tegaserod, and
      dexloxiglumide - are reviewed. RECENT FINDINGS: Alvimopan exerts mixed, but
      generally favorable, effects on restoration of gastrointestinal motility in
      patients with postoperative ileus. The observation of increased opioid
      requirements (without increased pain scores) and associated clinical
      ramifications requires further study. Tegaserod stimulates the peristaltic reflex
      and improves motility in multiple sites along the gastrointestinal tract. Its
      efficacy in improving gastrointestinal hypomotility in the critically ill
      population has not yet been determined. Furthermore, its use has been associated
      with the development of ischemic colitis and increased requirement for
      abdominal/pelvic surgery. Dexloxiglumide may be beneficial for improving gastric
      emptying in critically ill patients, especially those receiving lipid-enriched
      enteral feeds. SUMMARY: Novel prokinetic agents show promise for management of
      gastrointestinal hypomotility in the critically ill population. However, further
      study is required before these agents can be recommended for use.

PMID- 16810039
TI  - L-Arginine supplementation in sepsis: beneficial or harmful?
AB  - PURPOSE OF REVIEW: Recent results are reviewed on the effects of L-arginine
      supplements in excess of standard nutritional practices during severe sepsis and
      septic shock. RECENT FINDINGS: Septic shock has been alternatively viewed as an L
      arginine-deficient state or as a syndrome caused by excess nitric oxide, a
      vasoactive product of L-arginine metabolism. L-Arginine has many physiologic and
      pharmacologic effects that indicate its potential to affect survival in septic
      patients. Animal studies have documented immunologic effects of L-arginine and of
      commercial 'immune-enhancing' diets. However, survival studies in small animals
      have not consistently favored L-arginine. L-Arginine monotherapy in a canine
      model of septic shock found significant harm at infusion rates of less than twice
      that administered in standard formulations of total parenteral nutrition.
      Meanwhile, clinical studies have suffered from lack of statistical power, patient
      heterogeneity, randomization failures, and use of complex nutritional formulas.
      Meta-analyses have noted heterogeneity between the effects of immune-enhancing
      diets in surgical versus medical patients and mixed critically ill populations
      that include subjects with sepsis, indicating that these results may not be
      reliably pooled. SUMMARY: To date, published evidence has not established the
      safety and efficacy of L-arginine at doses above standard dietary practices in
      severe sepsis or septic shock.

PMID- 16810040
TI  - Statins in the intensive care unit.
AB  - PURPOSE OF REVIEW: Statins are effective lipid-lowering agents used extensively
      in medical practice. This review summarizes the evidence for statin treatment of
      cardiovascular patients in the intensive care unit and briefly discusses the role
      of statins in prevention and treatment of sepsis as a potential future
      application of statins in critical care. RECENT FINDINGS: Recent studies have
      extended the use of statin therapy to the acute manifestations of cardiovascular
      disease and have suggested cholesterol-independent therapeutic benefits, termed
      pleiotropic effects, which have added a wide scope of potential targets for
      statin therapy. SUMMARY: Statin therapy should be continued in intensive-care
      patients in whom statin therapy is warranted due to underlying cardiovascular
      disease or significant risk thereof. In acute coronary syndromes, statin therapy
      should be initiated within 24-96 h regardless of pretreatment cholesterol levels.
      Patients undergoing vascular surgery should receive peri-operative statin
      therapy. Placebo-controlled clinical trials are required to consolidate the
      experimental and observational evidence for prevention and treatment of sepsis.

PMID- 16810041
TI  - Lactate and shock state: the metabolic view.
AB  - PURPOSE OF REVIEW: The conventional view in severe sepsis or septic shock is that
      most of the lactate that accumulates in the circulation is due to cellular
      hypoxia and the onset of anaerobic glycolysis. A number of papers have suggested
      that lactate formation during sepsis is not due to hypoxia. I discuss this
      hypothesis and outline the recent advances in the understanding of lactate
      metabolism in shock. RECENT FINDINGS: Numerous experimental data have
      demonstrated that stimulation of aerobic glycolysis - that is, glycolysis not
      attributable to oxygen deficiency - and glycogenolysis occurs not only in
      resting, well-oxygenated skeletal muscles but also during experimental
      haemorrhagic shock and experimental sepsis, and is closely linked to stimulation
      of sarcolemmal Na+/K+ -ATPase under epinephrine stimulation. A human study of
      hyperkinetic septic shock demonstrated that skeletal muscle is a leading source
      of lactate production by exaggerated aerobic glycolysis through Na+/K+ -ATPase
      stimulation. SUMMARY: There is increasing evidence that sepsis is accompanied by
      a hypermetabolic state, with enhanced glycolysis and hyperlactataemia. This
      should not be rigorously interpreted as an indication of hypoxia. It now appears,
      at least in the hyperkinetic state, that increased lactate production and
      concentration as a result of hypoxia are often the exception rather than the
      rule.

PMID- 16810043
TI  - The inflammatory response to surgery and trauma.
AB  - PURPOSE OF REVIEW: The inflammatory or stress response to injury has evolved to
      ensure survival. This review will examine this response in otherwise healthy
      patients. Additionally, the impact of several common comorbid conditions on the
      inflammatory response will be considered. What will become evident is that the
      stress response may be exaggerated in some conditions and suppressed in others.
      Rapid identification of both an abnormal response and its cause will allow
      clinicians to maximize a patient's healing potential. RECENT FINDINGS: Recent
      work has shown that an altered inflammatory response has marked effects on both
      immune competence and the endocrine system. Investigations are ongoing to
      delineate the mechanism of lymphocyte dysfunction. With regard to critical care
      endocrinopathies, the effects of insulin and hyperglycemia on inflammation and
      wound healing are being investigated. SUMMARY: An understanding of the stress
      response will aid the clinician in preparing for expected responses, recognizing
      and perhaps correcting deviations from the norm and accounting for potential
      complications that arise in the face of preexisting disease. Deviations from the
      normal time course may represent the effects of preexisting medical illness,
      treatment or postoperative/injury complications.

PMID- 16810044
TI  - Evaluation of the abdomen in the critically ill patient: opening the black box.
AB  - PURPOSE OF REVIEW: Evaluation of the abdomen in critically ill patients can be
      challenging. This article reviews the available data and proposes evidence-based
      guidelines for evaluation of the abdomen in the critically ill patient. RECENT
      FINDINGS: The critically ill are often clinically unevaluable due to distracting
      injuries, respiratory failure, obtundation, or other conditions. Even when
      patients can be examined, the clinical exam can be unreliable and misleading.
      Critically ill patients who are sufficiently stable to undergo imaging benefit
      from computerized tomography unless biliary sepsis is suspected, when ultrasound
      is preferred. There is an important role for endoscopy and angiography in the
      setting of gastrointestinal hemorrhage, as well as magnetic resonance imaging for
      mesenteric ischemia. Critically ill patients who are too unstable for imaging may
      require bedside laparoscopy or diagnostic peritoneal lavage. Abdominal
      compartment syndrome should be considered in the differential diagnosis of the
      unstable critically ill patient. Empiric laparotomy may still need to be employed
      in diagnosis and management of unstable patients. SUMMARY: Timely and accurate
      diagnosis of life-threatening intraabdominal pathology is essential to care for
      critically ill patients. A multitude of laboratory, radiologic, and
      interventional modalities are available to evaluate the abdomen in the critically
      ill.

PMID- 16810045
TI  - Intensive care of the patient following open abdominal aortic surgery.
AB  - PURPOSE OF REVIEW: Abdominal aortic aneurysms still require open repair despite
      the advances that endovascular aneurysm repair has made in treating patients with
      significant operative risk. Older patients with significant comorbidities require
      open repair of their complex aneurysms when they fail to meet anatomic criteria
      for endovascular aneurysm repair. This review discusses the physiologic insult of
      abdominal aortic surgery. It aims to address which patients are the highest risk
      of postoperative morbidity, and advances in their intensive care unit management
      to reduce such morbidity. RECENT FINDINGS: Advanced age, chronic health
      dysfunction, emergency surgery, and multiple organ failure are independent
      predictors of postoperative mortality. Myocardial ischemia is the largest
      contributor to patient morbidity, with any rise in postoperative cardiac troponin
      I predicting increased in-hospital myocardial infarction and mortality. Highest
      risk patients benefit most from optimizing perioperative cardiac status with beta
      blockade. Perioperative treatment with fenoldopam may improve renal outcome.
      Tracheostomy to aid in weaning is associated with increased mortality but may
      improve outcome in patients with preoperative chronic obstructive pulmonary
      disease. SUMMARY: Demographic trends indicate that open aortic surgery will
      continue to be performed on older patients with complex aneurysms. Identifying
      patients at risk and optimizing their postoperative risk factors will improve
      outcomes.

PMID- 16810046
TI  - Damage-control laparotomy.
AB  - PURPOSE OF REVIEW: This article summarizes the current state of damage-control
      laparotomy as practiced in trauma surgery. Since the first description of
      deliberately abbreviated laparotomy 20 years ago, damage-control laparotomy has
      been widely applied. The purpose of this review is to discuss current concepts in
      damage-control laparotomy in trauma and general surgery patients. RECENT
      FINDINGS: The immediate, essential goals of control of surgical bleeding and
      containment of gastrointestinal soilage are achieved at a truncated laparotomy.
      Ongoing resuscitation of the injured patient with severe physiologic derangements
      is continued in the intensive care unit. Only when the lethal triad of
      hypothermia, metabolic acidosis, and coagulopathy is corrected does the patient
      subsequently undergo definitive surgery. Recent studies have better defined the
      subset of patients that benefit from such an approach. SUMMARY: Application of
      abbreviated laparotomy has been widely applied in the trauma population. Breaking
      the pathophysiologic cycle of hypothermia, coagulopathy, and acidosis with this
      approach has improved survivorship in this critically injured group of patients.
      The extension of the abbreviated laparotomy concept has also been described in
      the general surgery population, and raises the possibility of extending this
      concept to broader surgical fields.

PMID- 16810047
TI  - Recombinant factor VIIa and the surgical patient.
AB  - PURPOSE OF REVIEW: Bleeding remains a challenge in surgery. A unique drug,
      recombinant factor VIIa, causes clotting exclusively at bleeding sites.
      Recombinant factor VIIa has recently been introduced to surgery where current
      evidence, consisting mostly of case reports, suggest remarkable safety and
      efficacy. The first randomized controlled trials are only now being published
      with less remarkable results. This manuscript summarizes the current evidence.
      RECENT FINDINGS: In trauma, a single randomized control trial suggests
      recombinant factor VIIa reduces bleeding and transfusion in blunt trauma,
      particularly in coagulopathic patients. In cardiac surgery, one randomized
      control trial, open-label studies and case reports suggest benefit in refractory
      bleeding. For liver surgery, randomized control trials do not support use in
      liver transplant or gastrointestinal bleeding. In neurosurgery, one randomized
      control trial demonstrated improved outcome in intracerebral hemorrhage. In
      urology, one randomized control trial demonstrated significant reduction in
      perioperative bleeding. For orthopedics, a single randomized control trial showed
      no benefit in pelvic/acetabular surgery. In obstetrics/gynecology, limited
      evidence suggests benefit in massive bleedings. SUMMARY: Current evidence does
      not yet support recombinant factor VIIa as standard of care in surgery. However,
      the evidence indicates that recombinant factor VIIa should be used in
      intracerebral hemorrhage and massive perioperative or traumatic bleeding
      refractory to conventional therapies. For now, the bedside decision to use
      recombinant factor VIIa remains a matter of surgical judgment.

PMID- 16810054
TI  - Bibliography. Current world literature. Pharmacology, metabolism and nutrition.

PMID- 16810049
TI  - The role of the surgeon as intensivist: an international perspective.
AB  - PURPOSE OF REVIEW: Critical care is a young specialty. It emerged less than 50
      years ago in response to new technologies that could prolong the survival of
      patients who previously would have died. The diseases that posed this threat to
      life were varied and the original practitioners of critical care came from a
      variety of medical backgrounds, and created a multidisciplinary specialty. As it
      continues to evolve, however, the participation and influence of surgeons is
      waning. CONTENT: We have sought the perspectives of an international group of
      intensivists on the role of surgeons in the future of critical care. These
      perspectives are varied. Surgeons play the largest role in North American
      critical care, although even here that role is diminishing, and new models of
      practice are needed. Surgical involvement is even less in Japan, Europe, and
      South America. The important role of the surgical perspective in differentiating
      heroic from futile intervention is underlined by Alsanea from Saudi Arabia.
      CONCLUSIONS: Surgical involvement in the practice of critical care is declining
      around the world. The reasons are complex, and include competing clinical
      imperatives, economics, and the demands of training programs. New models are
      needed to revitalize critical care as a multidisciplinary specialty.

PMID- 16810055
TI  - Recent advances in the pathology and classification of ovarian sex cord-stromal
      tumors.
AB  - In recent years, our knowledge of ovarian sex cord-stromal tumors has increased,
      and their classification has evolved. In this review, recent advances in the
      classification and pathology of ovarian sex cord-stromal tumors are discussed,
      and the controversy regarding the classification of sex cord tumor with annular
      tubules is addressed. The current classification is built on those of the past,
      and future classifications should improve on what is now in place incorporating
      new knowledge from more sophisticated clinicopathologic studies and advanced
      molecular techniques. This review emphasizes articles written in the 21st century
      as well as those that have significantly advanced our knowledge of sex cord
      stromal tumors in past decades. The tumors in this group occur over a wide age
      range and are often unilateral. In difficult cases, immunocytochemistry provides
      improved diagnostic accuracy. The most useful immunohistochemical marker for
      their identification is alpha-inhibin, which is positive in most neoplasms in the
      sex cord-stromal group. The article concludes with a section discussing the
      pathogenesis of sex cord-stromal tumors.

PMID- 16810056
TI  - Intraoperative assessment of ovarian tumors: a 5-year review with assessment of
      discrepant diagnostic cases.
AB  - Frozen section is often requested in the intraoperative assessment of patients,
      presenting with ovarian masses, to provide guidance for appropriate surgical
      management. To assess the accuracy of frozen section and identify causes of
      diagnostic error, we reviewed 914 consecutive ovarian frozen sections performed
      over a 5-year period in 2 laboratories; one of which provides a general surgical
      pathology service and, the other, a specialist gynecologic pathology service.
      Cases, in which there were significant diagnostic discrepancies between the
      intraoperative and the final histological diagnoses, were reviewed. The series
      included 552 benign lesions (60.4%), 96 borderline (atypical proliferating)
      epithelial tumors (10.5%), and 266 malignancies (29.1%). The overall accuracy of
      frozen section diagnosis was 95.3%. There were 43 cases with diagnostic
      discrepancy; 20 (3.8% cases) of which were reported in the specialist laboratory
      and 23 (5.9% cases) in the general laboratory. Underdiagnosis of tumor type
      accounted for 32 of 43 discrepant cases and was most frequent in borderline
      mucinous tumors. The most common cause of overdiagnosis was the misinterpretation
      of serous cystadenofibroma as borderline serous tumor. Slide review of the 41
      assessable cases indicated that sampling error, pathologist misinterpretation,
      and suboptimal slide preparations contributed to misdiagnoses in 17, 23, and 9
      tumors, respectively (in 9 cases, 2 factors were contributory), whereas no
      specific error was identified in the remaining case. Technical factors and
      pathologist misinterpretation were more common in the general pathology
      laboratory. This study confirms that ovarian frozen section is a generally
      reliable technique, but there are problematic areas, particularly involving the
      assessment of borderline tumors.

PMID- 16810057
TI  - Patterns of loss of heterozygosity at 10q23.3 and microsatellite instability in
      endometriosis, atypical endometriosis, and ovarian carcinoma arising in
      association with endometriosis.
AB  - Genetic aberrations, such as loss of heterozygosity (LOH) and mutations leading
      to functional inactivation of the PTEN tumor suppressor gene, located on
      chromosome 10q23.3, have been shown to be associated with approximately one third
      of ovarian adenocarcinomas. In addition, microsatellite instability (MSI) leading
      to the functional inactivation of the PTEN gene has also been reported for
      ovarian adenocarcinomas with frequencies varying from 6 to 37%. However, the
      frequency of PTEN gene abnormalities has not been well studied or evaluated in
      lesions such as typical and atypical endometriosis. The aim of this study was to
      investigate a possible sequential progression from endometriosis through atypical
      endometriosis to ovarian carcinoma by assessing LOH at 10q23.3 and MSI in those
      entities. Genomic DNA was analyzed for LOH and MSI at 3 loci on chromosome 10,
      using polymerase chain reaction amplification. Significant differences in LOH
      were seen between endometriosis (4.3%) and ovarian carcinoma (23.5%) at D10S608.
      The differences at the other 2 loci were not significant. A high frequency of MSI
      was found in endometriosis (82.6%) and atypical endometriosis (75%); however, the
      differences were not significant. These results suggest that LOH at D105608 may
      possibly be an important molecular event in the progression of endometriosis to
      carcinoma. This study highlights that endometriosis and atypical endometriosis
      might act as precursor lesions that have the potential to progress into ovarian
      adenocarcinoma.

PMID- 16810058
TI  - A case of virilizing brenner tumor in a postmenopausal woman with stromal
      androgenic activity.
AB  - Although there are several reports of Brenner tumor showing estrogen activities,
      it is an extremely rare cause of androgen excess leading to virilism, and the
      source or mechanism of its androgen production is also unknown at present. A 74
      year-old woman presented with lower abdominal pain and increased facial hair
      growth of 6-month duration. Bilateral ovarian tumors were detected, and her serum
      testosterone (1.7 ng/mL) and estradiol (75 pg/mL) levels were elevated. Bilateral
      salpingo-oophorectomy was performed. The ovarian tumors were diagnosed as benign
      Brenner tumor associated with fibrothecoma-like and luteinized stromal cells.
      Postoperatively, the serum testosterone and estradiol levels decreased.
      Immunohistochemically, fibrothecoma-like stromal cells were positive for
      cytochrome P-450 aromatase, which catalyzes the conversion from androgen to
      estrogen, and negative for c-Jun protein, which has recently reported to
      attenuate estrogen biosynthesis by directly down-regulating transcription of the
      aromatase gene. On the other hand, luteinized stromal cells were negative for
      cytochrome P-450 aromatase and positive for c-Jun protein. It is suggested that
      androgen is produced mainly in the luteinized stromal cells, because androgen is
      not converted to estrogen caused by suppression of aromatase biosynthesis by c
      Jun.

PMID- 16810059
TI  - Hepatoid carcinoma with serous component of the fallopian tube: a case report
      with immunohistochemical and ultrastructural studies.
AB  - A very rare case of hepatoid carcinoma with serous component arising in the
      fallopian tube of a 79-year-old woman is presented. The lesion was a 5.0-cm
      unencapsulated, yellowish-white soft mass. The tumor was composed of hepatoid
      carcinoma (90%) and serous carcinoma (10%) components. The hepatoid carcinoma was
      histologically characterized by a proliferation of round to polygonal cells
      arranged in a trabecular, tubular, sinusoidal, papillary, or solid pattern. The
      serous component in the fallopian tube also showed in situ lesions. Both
      components showed an infiltration into the surface of the left ovary, omentum,
      peritoneum including the pouch of the Douglas, and serosa of the colon.
      Immunohistochemically, the hepatoid carcinoma was positive for alpha-fetoprotein,
      polyclonal carcinoembryonic antigen (CEA), hepatocyte paraffin 1, albumin,
      epithelial membrane antigen, and cytokeratin (CAM5.2). Ultrastructurally, the
      cytoplasm contained abundant ribosomes, moderate amounts of mitochondria, and
      rough endoplasmic reticulum that developed into a meshwork and contained
      mitochondria within it. Microbile channel-like structures and desmosomes were
      occasionally observed. The association with serous carcinoma indicates mullerian
      origin rather than germ cell origin. The patient received chemotherapy and was
      alive without disease at 10 months after surgery.

PMID- 16810060
TI  - Uterine lipoleiomyomas: a clinicopathologic study of 50 cases.
AB  - Lipoleiomyoma is an uncommon uterine neoplasm and, although presumed to be
      benign, has been inadequately studied. Confirming the benign nature of this tumor
      is important because it can closely resemble well-differentiated liposarcoma. We
      evaluated 50 consecutive lipoleiomyomas diagnosed at the Washington Hospital
      Center from 1998 to 2004; 2.1% of patients who had uterine leiomyomas during this
      period had a lipoleiomyoma. The mean and median patient age was 54 and 51 years,
      respectively. The mean and median tumor size was 4.6 and 2.1 cm, respectively.
      Forty-three (83%) tumors were located in the uterine corpus, and 7 (13%) were in
      the cervix. One broad ligament tumor and one retroperitoneal tumor were also
      studied. The mitotic index was zero for all tumors. No tumors displayed
      cytological atypia, necrosis, calcification, or other degenerative changes.
      Follow-up periods ranged from 1.8 to 7.5 years (mean, 5.0 years). Four patients
      died of unrelated causes. There were no recurrences or fatalities related to
      tumor. Lipoleiomyoma of the uterus seems to have an uneventful clinical course
      and can now be confidently regarded as benign.

PMID- 16810061
TI  - Idiopathic uterine granulomas: report of a series with morphological similarities
      to idiopathic ovarian cortical granulomas.
AB  - Granulomas in the uterine corpus and cervix are rare, with most examples
      obviously a result of a previous operative or ablative procedure. In this report,
      we describe 8 cases where granulomas, not associated with a previous procedure,
      were identified as an incidental finding in the myometrium or cervical stroma. A
      review of the clinical records revealed no obvious cause for the granulomatous
      inflammation, and we propose the term "idiopathic uterine granulomas." In all
      cases, the granulomas, which in most cases were multiple, were well circumscribed
      and intimately related to thin-walled vascular channels that showed no evidence
      of vasculitis. This resulted in a characteristic histological appearance similar
      to that seen with so-called "idiopathic ovarian cortical granulomas." Although
      local and systemic causes of granulomatous inflammation should be excluded,
      granulomas in the myometrium and cervical stroma may occur without an obvious
      underlying cause.

PMID- 16810062
TI  - Serous carcinoma of the endometrium with choriocarcinomatous differentiation: a
      case report and review of the literature indicate the existence of 2
      prognostically relevant tumor types.
AB  - Nongestational choriocarcinomas rarely occur outside the gonads or teratomas. We
      report a serous carcinoma of the endometrium with a choriocarcinomatous component
      and review of the literature. A 61-year-old woman underwent hysterectomy and
      bilateral salpingo-oophorectomy for a serous carcinoma with choriocarcinomatous
      component. Immunohistochemistry showed a strong p53 staining of the serous
      component and the cytotrophoblastic cells of the choriocarcinomatous component;
      the syncytiotrophoblast was negative. The initial serum human chorionic
      gonadotropin (hCG) was 225,000 IU/L. Postoperatively, the patient developed
      diffuse pulmonary metastatic disease. Despite chemotherapy, the patient died 2
      months after initial diagnosis. Abstracting the data from the reported cases and
      from the literature, it can be assumed that 2 different tumor types exist. The
      first one is morphologically and clinically more related to the gestational
      choriocarcinoma with strongly elevated serum hCG levels, early onset of (distant)
      metastatic disease, and consecutively rapid and often fatal clinical course. The
      second type presents as an endometrial carcinoma with single syncytiotrophoblast
      like cells, associated with low serum hCG, no distant metastatic disease, and,
      consequently, a better prognosis. The prognostically relevant component for long
      time survival in the latter variant is the nontrophoblastic component.

PMID- 16810063
TI  - p16-Positive small cell neuroendocrine carcinoma of the endometrium.
AB  - We report herein a small cell neuroendocrine carcinoma of the endometrium that
      extended to the cervix and showed strong immunohistochemical staining for p16.
      The p16 staining raised the possibility of a human papillomavirus (HPV)-related
      tumor, because in the cervix, a positive p16 immunohistochemical stain is
      presumptive evidence of HPV. However, the current case was HPV negative. We
      discuss the molecular pathogenesis of non-HPV-related increased p16 expression.

PMID- 16810064
TI  - A high-grade uterine leiomyosarcoma with human chorionic gonadotropin production.
AB  - Ectopic human chorionic gonadotropin production has been described in a wide
      variety of non-germ cell tumors, particularly in epithelial tumors, but rarely in
      sarcomas. In this report, we describe the case of 49-year-old woman with a
      history of "uterine fibroids," who presented with vaginal bleeding and a positive
      urine pregnancy test. After pregnancy was ruled out by ultrasound, the patient
      underwent a laparotomy and hysterectomy for a presumptive diagnosis of "fibroids"
      and was found to have carcinomatosis at the time of the surgery. Therefore
      optimal debulking of tumors was performed. Two weeks later, the patient developed
      a small bowel obstruction, which apparently was due to rapid recurrence of tumors
      in the abdomen, and soon afterwards she died. Microscopically, the resected
      pelvic mass was composed of highly atypical and pleomorphic spindle cells admixed
      with many multinucleated giant cells. The tumor had a high mitotic rate along
      with areas of hemorrhage and necrosis. Immunohistochemically, the tumor cells
      were positive for vimentin, desmin, smooth muscle actin, and beta-human chorionic
      gonadotropin, and were negative for epithelial membrane antigen, keratin AE1/3, S
      100, CD31, CD117, Ber-EP4, WT-1, estrogen and progesterone receptors. The
      majority of cells, including the multinucleated giant cells, were strongly
      immunoreactive for beta-human chorionic gonadotropin. Only three cases of
      leiomyosarcomas with beta/human chorionic gonadotropin production have been
      described in the literature, and all three cases had extrauterine origin. Our
      case, to the authors' best knowledge, is the first uterine leiomyosarcoma with
      prominent beta/human chorionic gonadotropin production.

PMID- 16810065
TI  - Cotyledonoid dissecting leiomyoma of the uterus: a case report of a benign
      uterine tumor with sarcomalike gross appearance and review of literature.
AB  - Cotyledonoid dissecting leiomyoma (Sternberg tumor) is a very rare variant of
      uterine smooth muscle tumor with an unusual and alarming gross appearance.
      Including our case, approximately 20 cases were reported in the literature. A 27
      year-old woman presented with pelvic mass. A 41-cm fungating rubbery mass with
      placenta-like appearance adhering to the posterior uterine surface and extending
      to the left broad ligament and pelvic cavity was observed. An intraoperative
      frozen section was requested, and a diagnosis of a benign smooth muscle tumor was
      given. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were
      performed with removal of the pelvic tumor extension. Thorough tumor sampling was
      performed and showed nodules of interlacing bundles of bland-looking smooth
      muscle cells, separated by expanded, edematous, and highly vascularized stroma.
      No atypia, mitotic activity, or coagulative necrosis was seen.
      Immunohistochemical studies confirmed the smooth muscle nature of the tumor.
      Cotyledonoid leiomyoma has a distinctive gross appearance which usually raises
      the suspicion of sarcoma. Intraoperative frozen section is a mandatory and
      helpful procedure to avoid overtreatment of such cases.

PMID- 16810066
TI  - An interview of Leopold G. Koss, M.D. [corrected].

PMID- 16810067
TI  - Radiation therapy induced changes in apoptosis and its major regulatory proteins,
      Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of
      the cervix.
AB  - BACKGROUND AND PURPOSE: Radiation therapy (RT) for cancer induces cell death by
      apoptosis. The major apoptotic regulatory molecules include Bcl-2, Bcl-XL
      (antiapoptotic), and Bax (proapoptotic) proteins. Invasive squamous cell
      carcinoma of the cervix is mainly treated by radiation, and hence our aim was to
      evaluate the changes induced by RT in the apoptotic index (AI) and to correlate
      this to the levels of the major pro- and antiapoptotic molecules. MATERIALS AND
      METHODS: Paired biopsies were obtained in 30 cases of invasive carcinoma cervix
      before and after 10 Gy RT. The TUNEL assay was performed to detect apoptotic
      nuclei and Bcl-2, Bcl-XL, and Bax proteins detected by immunohistochemistry
      (IHC). Statistical analysis was performed using the Spearman rank correlation
      coefficient test. RESULTS: Following RT, there was a significant increase in the
      mean AI [2.25 (+/-2.28) in post-RT vs 0.90 (+/-0.53) in the pre-RT group]. Bax, a
      major proapoptotic protein, was significantly increased following RT (P < 0.05),
      whereas the antiapoptotic Bcl-XL showed a significant decrease (P = 0.006). There
      was no significant change in Bcl-2 expression. The Bcl-2 and Bax IHC scores and
      the Bcl-2/Bax ratio did not correlate with AI in the 2 groups. There was an
      inverse correlation of Bcl-XL to AI in the pre-RT group (P = 0.003) but not in
      the post-RT group. CONCLUSIONS: RT for invasive squamous cell carcinoma of cervix
      results in increased apoptotic cell death with the up-regulation of Bax, a
      proapoptotic protein, and the down-regulation of Bcl-XL, an antiapoptotic
      protein, without any significant change in the levels of Bcl-2.

PMID- 16810068
TI  - Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal
      septal masses: a diagnostic pitfall.
AB  - Gastrointestinal stromal tumor (GIST) are the most common mesenchymal tumors of
      the gastrointestinal (GI) tract. Most GISTs arise in the stomach and small bowel,
      whereas a small number occur elsewhere in the GI tract. Rare cases are identified
      outside the GI tract and are collectively known as extragastrointestinal stromal
      tumors (EGISTs). Because of their malignant potential and recent advances in the
      management of GISTs with imatinib mesylate (Gleevec, Glivec), it is imperative
      that these tumors are correctly diagnosed. In this study, we reviewed the
      clinical and pathologic characteristics of 3 cases of EGIST presenting as
      vulvovaginal/rectovaginal septal masses that were originally misdiagnosed,
      presumably due to their unusual anatomic locations. The original diagnoses were
      leiomyoma in one case and leiomyosarcoma in 2 cases. The lesions were localized
      to the rectovaginal septum () or vagina () and ranged from 4 to 8 cm in diameter.
      All 3 lesions had a spindle cell morphology that mimicked a smooth muscle tumor.
      Mitotic figures numbered from 12/50 to 16/50 high power fields (HPFs; median 15).
      Immunohistochemistry revealed that all 3 cases were strongly positive for KIT
      (CD117) and CD34 and negative for smooth muscle actin, desmin, pan-cytokeratin,
      and estrogen receptor. KIT sequence analysis revealed oncogenic mutations in all
      3 cases. The first tumor recurred at 2 years and the second tumor recurred at 10
      years; the third case is too recent for meaningful follow-up. EGISTs that present
      as gynecologic masses are rare but may be more common than is currently
      recognized. Misdiagnosis may lead to inappropriate therapy because conventional
      chemotherapy and radiotherapy are not effective in the treatment of GISTs,
      whereas imatinib mesylate (Gleevec, Glivec) has a proven role in managing these
      tumors. Thus, it is imperative to consider EGISTs in the differential diagnosis
      of mesenchymal neoplasms in the vulvovaginal/rectovaginal septum.

PMID- 16810069
TI  - Carcinomas of the female genital tract occurring after pelvic irradiation: a
      report of 15 cases.
AB  - The concept of postradiation sarcoma is widely appreciated, however carcinomas
      arising in previously irradiated fields, the putative "postradiation carcinoma,"
      are less well understood. Fifteen patients who developed gynecological
      malignancies after pelvic radiation therapy were studied. Five of these patients
      had HPV-related tumors both pre- and post- irradiation. Ten were irradiated for
      cervical cancer, one for endometrial carcinoma, one for vulvar carcinoma, one for
      colon cancer and 2 for benign conditions. The mean and median latent periods from
      the initiation of radiation therapy to the development of the second malignancy
      were 22.8 and 19 years, respectively (22.4 and 19.5 years, respectively, for non
      HPV-related cancers; 24 and 18 years for HPV-related cancers). The
      "postradiation" malignancies included 2 ovarian carcinomas, 5 vaginal carcinomas
      (3 invasive, 2 in situ), 4 endometrial carcinomas, one cervical carcinoma, one
      vulvar carcinoma, one distal urethral carcinoma, and one pelvic carcinoma of
      unclear primary site. Gynecological carcinomas may occur many years after pelvic
      irradiation. Although the evidence for a causative role is circumstantial, these
      tumors appear to have a similar latent period as postradiation sarcomas.

PMID- 16810070
TI  - Giant cell carcinoma of the uterine cervix: a case report.

PMID- 16810071
TI  - Neuropeptide Y induced attenuation of catecholamine synthesis in the rat
      mesenteric arterial bed.
AB  - The effect of neuropeptide Y (NPY) on the basal and nerve stimulation-induced
      increase in norepinephrine synthesis was studied in the isolated and perfused
      mesenteric arterial bed of the rat. Tyrosine hydroxylation, the rate-limiting
      step in catecholamine (CA) biosynthesis, was assessed by measuring the
      accumulation of DOPA in the perfusate/superfusate overflow after perfusion of the
      mesenteric arterial bed with the decarboxylase inhibitor m-hydroxybenzyl
      hydralazine (NSD-1015). Treatment with NDS-1015 resulted in a time-dependent
      increase in DOPA production and nerve stimulation (8 Hz, supramaximal voltage, 2
      ms duration) increased DOPA production even further. NPY 1 to 100 nM was observed
      to produce a concentration-dependent attenuation in both the basal and nerve
      stimulation-induced increase in DOPA formation. To come to an understanding of
      the NPY receptor subtype mediating the inhibition of CA synthesis, the rank order
      of potency of a series of NPY analogs with varying selectivity for NPY receptor
      subtypes including intestinal polypeptide (PYY), PYY 13-36, Leu36 Pro34 NPY,
      human pancreatic polypeptide (h-PP), and rat pancreatic polypeptide (r-PP) were
      determined. In addition, the effect of various selective NPY antagonists on the
      inhibitory effect of NPY was also examined. These included the Y1 antagonist
      BIB03304, the Y2 antagonist BIIE0246, and the Y5 antagonist CGP71683. The IC50's
      for NPY, PYY, PYY13-36, Leu31 Pro34 NPY, and hPP in inhibiting CA synthesis were
      5, 7, 15, 30, and 33 nM respectively. rPP failed to inhibit CA synthesis. All 3
      of the NPY antagonists produced attenuation of the NPY-induced inhibition of CA
      synthesis, but it took a combination of all 3 to completely block the effect of a
      maximal inhibitory concentration of NPY. These results demonstrate that NPY
      inhibits CA synthesis in the perfused mesenteric arterial bed and can do so by
      activation of a variety of receptors including the Y1, Y2, and Y5.

PMID- 16810072
TI  - A novel endothelin receptor antagonist CPU0213 improves diabetic cardiac
      insufficiency attributed to up-regulation of the expression of FKBP12.6, SERCA2a,
      and PLB in rats.
AB  - The depressed sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) and Ca2+-release
      channels (ryanodine receptor RyR2) are involved in the diabetic cardiomyopathy.
      However, an implication of a down-regulation of FK506-binding protein or
      calstabin-2 (FKBP12.6) is undefined. It was hypothesized that the down-regulation
      of FKBP12.6 and SERCA2a of the intracellular calcium handling system is closely
      related to an up-regulated endothelin (ET) system. An ET receptor antagonist
      CPU0213 is newly discovered and expected to ameliorate cardiac insufficiency
      which is mediated by the depressed FKBP12.6 and SERCA2a in diabetic rat heart.
      Diabetes was developed in male Sprague-Dawley rats 8 weeks after an injection of
      streptozotocin (60 mg/kg IP), and CPU0213 was instituted 30 mg/kg, SC in the last
      4 weeks. The assessment of the cardiac function, cardiac calcium handling
      proteins, endothelin system, and redox enzyme system were conducted. The
      compromised cardiac function in diabetic rats was accompanied by a significant
      down-regulation of expression of FKBP12.6 as well as SERCA2a and phospholamban.
      These were closely linked with an increased ET-1 and up-regulation of endothelin
      converting enzyme, PropreET1, and inducible nitric oxide synthase mRNA in
      diabetic cardiomyopathy. After 4-week treatment, CPU0213 was capable to attenuate
      completely the down-regulated FKBP12.6 and SERCA2a, and up-regulated ET system in
      association with a recovery of the cardiac insufficiency of diabetic
      cardiomyopathy.

PMID- 16810073
TI  - High-dose erythropoietin has no long-term protective effects in sheep with
      reperfused myocardial infarction.
AB  - High-dose erythropoietin has been claimed to be cardioprotective in experimental
      acute myocardial infarction. In large mammals, however, results are controversial
      and long-term follow-up data are lacking. We thus assessed the long-term effects
      of high-dose erythropoietin on left ventricular infarct size and function in an
      ovine model of reperfused myocardial infarction. After 90 minutes of coronary
      occlusion followed by reperfusion, sheep received recombinant human
      erythropoietin (rhEPO) 3000 units/kg on 3 consecutive days (rhEPO group, n=7) or
      vehicle (placebo group, n=6). Ten weeks later, ventricular function was assessed
      by echocardiography and catheterization. Infarct size, evaluated as percent
      fibrotic myocardium (morphometry) and by hydroxyproline quantification, was
      similar in both groups (morphometry: rhEPO: 22.1 +/- 5.5%, placebo: 18.1 +/-
      3.3%, P not significant; hydroxyproline: rhEPO: 6.6 +/- 1.3 microg/mg wet weight,
      placebo: 7.1 +/- 0.9 microg/mg, P not significant). Ventricular function was
      diminished in the rhEPO group, as indicated by lower septal wall thickening at
      the infarct border zone (rhEPO: -1.9 +/- 16.4%, placebo: 20.5 +/- 17%, P<0.04),
      higher end systolic volume (rhEPO: 47 +/- 14.3 mL, placebo: 32.6 +/- 7.3 mL,
      P<0.05), and higher end diastolic pressure (rhEPO: 17 +/- 6.5 mm Hg, placebo:
      10.1 +/- 2.8 mm Hg, P<0.03). In the rhEPO group, left ventricular endocardial
      area was larger, suggesting dilatation. High-dose erythropoietin has no
      cardioprotective effects in sheep with reperfused myocardial infarction.

PMID- 16810074
TI  - Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on
      venous function.
AB  - Loss of endothelial cell-derived nitric oxide (NO) in hypertension is a hallmark
      of arterial dysfunction. Experimental hypertension created by the removal of NO,
      however, involves mechanisms in addition to decreased arterial vasodilator
      activity. These include augmented endothelin-1 (ET-1) release, increased
      sympathetic nervous system activity, and elevated tissue oxidative stress. We
      hypothesized that increased venous smooth muscle (venomotor) tone plays a role in
      Nomega-nitro-L-arginine (LNNA) hypertension through these mechanisms. Rats were
      treated with the NO synthase inhibitor LNNA (0.5 g/L in drinking water) for 2
      weeks. Mean arterial pressure of conscious rats was 119 +/- 2 mm Hg in control
      and 194 +/- 5 mm Hg in LNNA rats (P<0.05). Carotid arteries and vena cava were
      removed for measurement of isometric contraction. Maximal contraction to
      norepinephrine was modestly reduced in arteries from LNNA compared with control
      rats whereas the maximum contraction to ET-1 was significantly reduced (54%
      control). Maximum contraction of vena cava to norepinephrine (37% control) also
      was reduced but no change in response to ET-1 was observed. Mean circulatory
      filling pressure, an in vivo measure of venomotor tone, was not elevated in LNNA
      hypertension at 1 or 2 weeks after LNNA. The superoxide scavenger tempol (30,
      100, and 300 micromol kg(-1), IV) did not change arterial pressure in control
      rats but caused a dose-dependent decrease in LNNA rats (-18 +/- 8, -26 +/- 15,
      and -54 +/- 11 mm Hg). Similarly, ganglionic blockade with hexamethonium caused a
      significantly greater fall in LNNA hypertensive rats (76 +/- 9 mm Hg) compared
      with control rats (35 +/- 10 mm Hg). Carotid arteries, vena cava, and sympathetic
      ganglia from LNNA rats had higher basal levels of superoxide compared with those
      from control rats. These data suggest that while NO deficiency increases
      oxidative stress and sympathetic activity in both arterial and venous vessels,
      the impact on veins does not make a major contribution to this form of
      hypertension.

PMID- 16810075
TI  - Effects of MCI-154 on vascular reactivity and its mechanisms after hemorrhagic
      shock in rats.
AB  - The objectives of this study were to investigate the effects of 6-[4-(4'
      pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride trihydrate (MCI
      154), a newly developed cardiotonic agent, on vascular reactivity and contractile
      responses to extracellular Ca2+ ([Ca2+]o) after hemorrhagic shock and primarily
      explore its mechanism. In vivo, the effects of MCI-154 (0.1, 0.5, 1.0, and 2.0
      mg/kg) on the pressor effect of norepinephrine (NE) in rats subjected to
      hemorrhagic shock (30 mm Hg for 2 h) were observed and in vitro, the effects of
      MCI-154 (10(-7), 10(-6), 10(-5), 10(-4) mol/L) on vascular reactivity and
      contractile responses to [Ca2+]o of superior mesenteric artery (SMA) from
      hemorrhagic shock rats and its relationship to Rho-kinase, protein kinase C
      (PKC), and protein kinase G (PKG) were observed. The results showed that the NE
      induced pressor response after hemorrhagic shock was significantly decreased
      (P<0.01), and MCI-154 made it decrease further. In vitro, MCI-154 further
      decreased the contractile responses of SMA to NE and Ca2+ after hemorrhagic shock
      as compared with untreated hemorrhagic shock group (P<0.01). Angiotensin II (Ang
      II), with Rho-kinase stimulating action, and PMA, a PKC agonist increased the
      contractile responses to [Ca2+]o of SMA after hemorrhagic shock. MCI-154 (10(-5)
      mol/L) partly inhibited Ang II and PMA-induced increase of the contractile
      responses to [Ca2+]o of SMA (P<0.01). KT-5823, the PKG antagonist, antagonized
      MCI-154-induced decrease of the contractile responses to [Ca2+]o. Taken together,
      these results suggested that the vascular reactivity and contractile responses to
      [Ca2+]o of vascular smooth muscle after hemorrhagic shock were significantly
      decreased. MCI-154 worsened hemorrhagic shock-induced vascular hyporeactivity and
      the decrease of contractile responses to [Ca2+]o. These effects were possibly
      regulated by Rho-kinase, PKC, and PKG, but this needs further confirmation.

PMID- 16810076
TI  - Effects of fenofibrate on C-reactive protein levels in hypertriglyceridemic
      patients.
AB  - We investigated the effects of fenofibrate on C-reactive protein (CRP) levels in
      patients with hypertriglyceridemia. Patients with a triglyceride level >or=200
      mg/dL were randomly assigned to receive either 200 mg of fenofibrate (n = 54) or
      general measures (n = 54). A third group of patients with hypercholesterolemia
      received a statin (n = 54). Patients with a CRP level >or=10 mg/L were excluded.
      CRP levels were measured before and after 2 months of therapy. Fenofibrate did
      not reduce CRP levels (1.74 +/- 1.74 vs. 1.54 +/- 1.66 mg/L, P = 0.27) nor did
      general measures (P = 0.85). Statin reduced CRP levels (P = 0.002). In patients
      with baseline CRP levels of >or=3 mg/dL, CRP levels were decreased in both the
      fenofibrate and control groups (P = 0.026 and 0.008, respectively). Changes in
      CRP levels were associated only with baseline CRP levels in both groups (P =
      0.001 and 0.049, respectively). When all hypertriglyceridemic patients were
      divided into 2 subgroups according to changes in body weights, CRP levels
      decreased in patients who reduced their body weight >or=1 kg (n = 29, P = 0.030),
      and were not changed in the other patients (n = 79, P = 0.67). In summary,
      fenofibrate failed to decrease CRP levels in patients with hypertriglyceridemia.
      An anti-inflammatory mechanism may not play a significant role in the
      cardioprotective effect of fenofibrate.

PMID- 16810077
TI  - Severity of hyperlipidemia does not affect antiatherosclerotic effect of an
      angiotensin II receptor antagonist in apolipoprotein E-deficient mice.
AB  - The purpose of this study was to clarify whether severity of hyperlipidemia
      affects the antiatherosclerotic effect of angiotensin II receptor blockers
      (ARBs). The effect of olmesartan medoxomil, an ARB, on atherosclerotic lesion was
      examined in apolipoprotein E-deficient (ApoEKO) mice fed a normal diet (ND) or a
      high-fat-supplemented diet (FD) for 25 weeks. ApoEKO mice have high plasma
      cholesterol levels, which were further increased by feeding of an FD. Both the
      atherosclerotic lesion area of the aortic luminal surface and the atherosclerotic
      lesion thickness in the aortic valves were significantly greater in the FD mice
      than in the ND mice. Olmesartan medoxomil did not affect the plasma cholesterol
      levels in either the ND or FD ApoEKO mice; however, it reduced effectively both
      the atherosclerotic lesion surface area and the lesion thickness even in FD
      ApoEKO mice. It is concluded that the antiatherosclerotic effect of ARBs is not
      weakened by the high plasma cholesterol level, suggesting the usefulness of ARBs
      in the treatment of atherosclerosis, even in a situation in which the plasma
      cholesterol level is not fully controlled.

PMID- 16810078
TI  - Pitavastatin improves cardiac function and survival in association with
      suppression of the myocardial endothelin system in a rat model of hypertensive
      heart failure.
AB  - Statin therapy may be associated with lower mortality in patients with heart
      failure, but the underlying mechanism of such an association is unknown. We have
      evaluated the effects of pitavastatin on cardiac function and survival in a rat
      model of hypertensive heart failure and investigated the molecular mechanism of
      the observed effects. Dahl salt-sensitive rats fed with high-salt diet from 7
      weeks of age developed compensatory left ventricular hypertrophy at 12 weeks and
      heart failure at 19 weeks. Dahl salt-sensitive rats were treated with either
      vehicle or pitavastatin (0.3 mg/kg per day) from 7 or 12 weeks. Both early-onset
      and late-onset pitavastatin treatment reduced left ventricular fibrosis, improved
      cardiac function, and increased the survival rate apparent at 19 weeks. The
      increases in the expression levels of hypertrophic, profibrotic, and
      metalloproteinase genes as well as in gelatinase activities in the heart induced
      by the high-salt diet were suppressed by pitavastatin treatment. Furthermore, the
      level of cardiac endothelin-1 was increased in association with the development
      of heart failure in a manner sensitive to treatment with pitavastatin. Both early
      and late pitavastatin treatment thus improved cardiac function and survival, with
      modulation of extracellular matrix remodeling and endothelin-1 signaling possibly
      contributing to these beneficial effects.

PMID- 16810079
TI  - Antihypertensive responses elicited by central moxonidine in rats: possible role
      of nitric oxide.
AB  - In the present study, we investigated the effects of pretreatment with NG-nitro-L
      arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) injected
      intravenously (IV) on the hypotension, bradycardia, and vasodilation produced by
      moxonidine (alpha2-adrenergic/imidazoline receptor agonist) injected into the
      fourth brain ventricle (4th V) in rats submitted to acute hypertension that
      results from baroreflex blockade by bilateral injections of kynurenic acid (kyn,
      glutamatergic receptor antagonist) into the nucleus of the solitary tract (NTS)
      or in normotensive rats. Male Wistar rats (n=5 to 7/group) anesthetized with IV
      urethane (1.0 g kg(-1) of body weight) and alpha-chloralose (60 mg kg(-1) of body
      weight) were used. Bilateral injections of kyn (2.7 nmol 100 nL(-1)) into the NTS
      increased baseline mean arterial pressure (148 +/- 11 mm Hg, vs. control: 102 +/-
      4 mm Hg) and baseline heart rate (417 +/- 11 bpm, vs. control: 379 +/- 6 bpm).
      Moxonidine (20 nmol microL(-1)) into the 4th V reduced mean arterial pressure and
      heart rate to similar levels in rats treated with kyn into the NTS (68 +/- 9 mm
      Hg and 359 +/- 7 bpm) or in control normotensive rats (66 +/- 7 mm Hg and 362 +/-
      8 bpm, respectively). The pretreatment with L-NAME (25 micromol kg, IV)
      attenuated the hypotension produced by moxonidine into the 4th V in rats treated
      with kyn (104 +/- 6 mm Hg) or in normotensive rats (95 +/- 8 mm Hg), without
      changing bradycardia. Moxonidine into the 4th V also reduced renal, mesenteric,
      and hindquarter vascular resistances in rats treated or not with kyn into the NTS
      and the pretreatment with L-NAME IV reduced these effects of moxonidine.
      Therefore, these data indicate that nitric oxide mechanisms are involved in
      hypotension and mesenteric, renal, and hindquarter vasodilation induced by
      central moxonidine in normotensive and in acute hypertensive rats.

PMID- 16810080
TI  - The pathway-selective estrogen receptor ligand WAY-169916 displays differential
      activity in ischemia-reperfusion injury models.
AB  - We previously reported on the development of a pathway-selective estrogen
      receptor (ER) ligand, WAY-169916, that has ER-dependent antiinflammatory activity
      and is devoid of classic ER transcriptional activity. In the current study, WAY
      169916 and 17beta-estradiol (17beta-E2) were evaluated for protective activity in
      models of cardiac ischemia-reperfusion injury. In rats subjected to cardiac
      ischemia-reperfusion injury by occlusion of the left coronary artery, infarct
      size relative to the area at risk in the left ventricle was significantly
      attenuated by a single dose of 17beta-E2 (20 microg/kg, SC), and WAY-169916
      administered SC (10 mg/kg) or IV (1 mg/kg) during the ischemia phase. In isolated
      hearts perfused on a Langendorff apparatus and subjected to global ischemia and
      reperfusion, 17beta-E2 and WAY-169916 both had direct cardioprotective activity
      when perfused at 1 microM but their effects varied between different end points.
      Perfusion with 17beta-E2 only improved recovery of left ventricle-developed
      pressure. Perfusion with WAY-169916 attenuated the elevation in perfusion
      pressure, diastolic pressure, and release of creatine kinase after ischemia. In
      contrast to 17alpha-ethinylestradiol, WAY-169916 had no classic estrogen effects
      on uterine weight or total serum cholesterol in rats treated for 4 days. The data
      demonstrate that the pathway-selective ER ligand WAY-169916 displays differential
      activity in vivo on different cardiovascular end points.

PMID- 16810081
TI  - Confronting HIV/AIDS one patient at a time.

PMID- 16810082
TI  - Kentucky bill grants authorization to prescribe scheduled drugs.

PMID- 16810083
TI  - The ABCs of melanoma recognition.

PMID- 16810084
TI  - Gestational diabetes management: guidelines to a healthy pregnancy.

PMID- 16810086
TI  - A step-by-step approach to HIV/AIDS.

PMID- 16810088
TI  - Menopause healthcare for women with physical disabilities.

PMID- 16810090
TI  - Access to rehabilitation services in rural practice.

PMID- 16810091
TI  - Hepatitis in primary care: what NPs can do to save lives.

PMID- 16810093
TI  - Validity issues relating to time-to-pregnancy studies of fertility.

PMID- 16810094
TI  - Pharmacokinetic variability and the miracle of modern analytical chemistry.

PMID- 16810095
TI  - Instrumental variable analysis of secondary pharmacoepidemiologic data.

PMID- 16810097
TI  - A conversation with John Pemberton. Interview by David Gunnell.

PMID- 16810099
TI  - Exposure intensity revisited.

PMID- 16810101
TI  - Binge drinking and dementia.

PMID- 16810102
TI  - Disseminated intravascular coagulation: a matter for immune globulins in sepsis?

PMID- 16810104
TI  - Immunoglobulin preparations attenuate organ dysfunction and hemostatic
      abnormality by suppressing the production of cytokines in lipopolysaccharide
      induced disseminated intravascular coagulation in rats.
AB  - OBJECTIVE: We attempted to clarify the effect of immunoglobulin concentrates on
      the rat lipopolysaccharide (LPS)-induced disseminated intravascular coagulation
      (DIC) model. DESIGN: Prospective, comparative, experimental study. SETTING:
      Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6 to 7 wks
      and weighing 160 to 170 g. INTERVENTIONS: Two kinds of experiments were
      performed. In the first, experimental DIC was induced by sustained infusion of 30
      mg/kg LPS for 4 hrs via the tail vein, and two doses of immunoglobulin (25 or 100
      mg/kg/4.5 hrs) were administered to rats 30 mins before infusion of LPS, after
      which immunoglobulin infusion was continued for a further 4 hrs. In the second,
      experimental DIC was induced by sustained infusion (5 mg/kg/1 hr) of LPS for 1
      hr, and one dose of immunoglobulin (100 mg/kg/4 hrs) was administered to rats
      after LPS induction. The parameters were estimated at 4 hrs and 8 hrs in the
      first experiment and at 1, 5, and 10 hrs in the second one. MEASUREMENT AND MAIN
      RESULTS: Similar results were observed in the two experiments. Consumption
      coagulopathy and hemostatic activation were attenuated, especially when
      immunoglobulin was administered before LPS infusion. Plasma levels of creatinine
      and alanine aminotransferase were significantly depressed by coadministration of
      immunoglobulin. Marked glomerular fibrin deposition was observed in the LPS
      induced DIC model, but this deposition was reduced by immunoglobulin. In the
      first stage of the experiment, plasma levels of tumor necrosis factor (TNF) and
      interleukin (IL)-6 were suppressed by coadministration of immunoglobulin. In the
      second, plasma levels of IL-6 were significantly suppressed by immunoglobulin.
      CONCLUSION: It was concluded that plasma levels of TNF and IL-6 could be
      significantly suppressed by immunoglobulin in the LPS-induced DIC model.
      Moreover, hemostatic abnormality, organ dysfunction, and glomerular fibrin
      deposition in this model were all ameliorated by immunoglobulin.

PMID- 16810105
TI  - Safety and efficacy of affinity-purified, anti-tumor necrosis factor-alpha, ovine
      fab for injection (CytoFab) in severe sepsis.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) is a critical inflammatory mediator in
      sepsis. This trial was designed to evaluate the safety and effectiveness of
      polyclonal ovine anti-TNF fragment antigen binding (Fab) fragments (CytoFab) on
      plasma TNF-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) concentrations
      and the number of shock-free and ventilator-free days in severely septic
      patients. DESIGN: Phase II, randomized, blinded, placebo-controlled trial
      conducted from September 1997 to July 1998. SETTING: Nineteen intensive care
      units in the United States and Canada. PATIENTS: Eighty-one septic patients with
      either shock or two organ dysfunctions. INTERVENTIONS: Patients were randomized
      to receive CytoFab, infused as a 250-units/kg loading dose, followed by nine
      doses of 50 units/kg every 12 hrs, or 5 mg/kg human albumin as placebo.
      MEASUREMENTS AND MAIN RESULTS: CytoFab promptly reduced plasma TNF-alpha (p =
      .001) and IL-6 concentrations (p = .002) compared with placebo. CytoFab also
      significantly decreased TNF-alpha in bronchoalveolar lavage (BAL) fluid (p <
      .001). The number of shock-free days did not differ between CytoFab and placebo
      (10.7 vs. 9.4, respectively) (p = .270). CytoFab increased mean ventilator-free
      days (15.0 vs. 9.8 for placebo; p = .040) and ICU-free days (12.6 vs. 7.6 for
      placebo; p = .030) at day 28. All-cause, 28-day mortality rates were 37% (14/38)
      for placebo recipients, compared with 26% (11/43) for CytoFab recipients (p =
      .274). No differences in incidences of adverse events, laboratory, or vital sign
      abnormalities were observed between groups. Although 41% of CytoFab-treated
      patients developed detectable plasma levels of human anti-sheep antibodies, none
      demonstrated clinical manifestations during the 28-day study. CONCLUSIONS:
      CytoFab is well tolerated in patients with severe sepsis, effectively reducing
      serum and BAL TNF-alpha and serum IL-6 concentrations and increasing the number
      of ventilator-free and ICU-free days at day 28.

PMID- 16810106
TI  - Recombinant human activated protein C improves pulmonary function in ovine acute
      lung injury resulting from smoke inhalation and sepsis.
AB  - OBJECTIVE: To investigate the effects of recombinant human activated protein C
      (rhAPC) on pulmonary function in acute lung injury (ALI) resulting from smoke
      inhalation in association with a bacterial challenge. DESIGN: Prospective,
      randomized, controlled, experimental animal study with repeated measurements.
      SETTING: Investigational intensive care unit at a university hospital. SUBJECTS:
      Eighteen sheep (37.2 +/- 1.0 kg) were operatively prepared and randomly allocated
      to either the sham, control, or rhAPC group (n = 6 each). After a tracheotomy had
      been performed, ALI was produced in the control and rhAPC group by insufflation
      of 4 sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live
      Pseudomonas aeruginosa bacteria (containing 2-5 x 10(11) colony forming units)
      was instilled into the lungs according to an established protocol. The sham group
      received only the vehicle, i.e., 4 sets of 12 breaths of room air and
      instillation of 30 mL normal saline. The sheep were studied in the awake state
      for 24 hrs and were ventilated with 100% oxygen. RhAPC (24 mug/kg/hr) was
      intravenously administered. The infusion was initiated 1 hr post-injury and
      lasted until the end of the experiment. The animals were resuscitated with
      Ringer's lactate solution to maintain constant pulmonary artery occlusion
      pressure. MEASUREMENTS AND MAIN RESULTS: In comparison with nontreatment in
      controls, the infusion of rhAPC significantly attenuated the fall in Pao2/Fio2
      ratio (control group values were 521 +/- 22 at baseline [BL], 72 +/- 5 at 12 hrs,
      and 74 +/- 7 at 24 hrs, vs. rhAPC group values of 541 +/- 12 at BL, 151 +/- 29 at
      12 hours [p < .05 vs. control], and 118 +/- 20 at 24 hrs), and significantly
      reduced the increase in pulmonary microvascular shunt fraction (Qs/Qt; control
      group at BL, 0.14 +/- 0.02, and at 24 hrs, 0.65 +/- 0.08; rhAPC group at BL, 0.24
      +/- 0.04, and at 24 hrs, 0.45 +/- 0.02 [p < .05 vs. control]) and the increase in
      peak airway pressure (mbar; control group at BL, 20 +/- 1, and at 24 hrs, 36 +/-
      4; rhAPC group at BL, 21 +/- 1, and at 24 hrs, 28 +/- 2 [p < .05 vs. control]).
      In addition, rhAPC limited the increase in lung 3-nitrotyrosine (after 24 hrs
      [%]: sham, 7 +/- 2; control, 17 +/- 1; rhAPC, 12 +/- 1 [p < .05 vs. control]), a
      reliable indicator of tissue injury. However, rhAPC failed to prevent lung edema
      formation. RhAPC-treated sheep showed no difference in activated clotting time or
      platelet count but exhibited less fibrin degradation products (1/6 animals) than
      did controls (4/6 animals). CONCLUSIONS: Recombinant human activated protein C
      attenuated ALI after smoke inhalation and bacterial challenge in sheep, without
      bleeding complications.

PMID- 16810107
TI  - Antiretrovirals induce direct endothelial dysfunction in vivo.
AB  - HIV-associated cardiovascular diseases have been widely described, but clinical
      studies aimed at establishing cause-effect relationships between HIV-associated
      cardiovascular disease and either the HIV infection or antiretroviral therapy
      have been problematic. Endothelial dysfunction is a sensitive marker and early
      event in atherosclerosis, and many have suggested that protease inhibitors
      promote endothelial dysfunction indirectly by inducing elevations in circulating
      lipids. To determine whether nucleoside reverse transcriptase inhibitors and/or
      protease inhibitors induce endothelial dysfunction, and to test whether this
      effect is dependent upon drug-mediated alteration in plasma lipid concentrations,
      we treated male Sprague-Dawley rats with pharmacological doses of azidothymidine
      (AZT), indinavir, or AZT plus indinavir through their drinking water for 1 month
      and assessed endothelial function in aortic rings using an isometric force
      measurement. Circulating levels of plasma lipids and endothelin-1, a marker for
      endothelial injury and/or dysfunction, were also determined. We found that AZT
      and AZT plus indinavir treatments dramatically reduced endothelium-dependent
      vessel relaxation. However, AZT treatment did not significantly alter plasma
      levels of cholesterol or triglyceride. In addition, plasma endothelin-1 levels
      were elevated in rats treated with AZT plus indinavir. Indinavir treatment alone
      increased plasma cholesterol levels but had no effect on endothelial function.
      These findings suggest that in addition to modulating plasma lipid levels,
      antiretrovirals, particularly AZT and perhaps other nucleoside reverse
      transcriptase inhibitors, may have direct effects on the vascular endothelium.
      Together with other increased risk factors for atherosclerosis in HIV patients,
      AZT-induced endothelial dysfunction may contribute to the cardiovascular diseases
      associated with HIV antiretroviral therapy.

PMID- 16810108
TI  - Evaluation of oral tenofovir disoproxil fumarate and topical tenofovir GS-7340 to
      protect infant macaques against repeated oral challenges with virulent simian
      immunodeficiency virus.
AB  - Simian immunodeficiency virus (SIV) infection of infant macaques is a useful
      animal model of pediatric HIV infection to evaluate the potential of
      chemoprophylactic regimens to reduce mother-to-infant transmission of HIV.
      Previous studies have demonstrated that short-term subcutaneous administration of
      the reverse transcriptase inhibitor tenofovir was highly effective in protecting
      newborn macaques against infection after a single high-dose oral inoculation with
      virulent SIVmac251. In the current study, we mimicked HIV transmission through
      breast-feeding by repeatedly feeding infant macaques low doses of SIVmac251.
      Topical administration of a low dose of the second-generation tenofovir prodrug
      GS-7340 did not have detectable prophylactic efficacy. Oral administration of
      tenofovir disoproxil fumarate (DF; 10 mg/kg SID) lowered the infection rate at
      birth, but had lower efficacy against virus infection at 4 weeks of age, most
      likely because drug levels became suboptimal relative to those obtained with the
      current tenofovir DF regimen in humans. These prophylactic results further
      underscore the relevance of the current tenofovir DF prevention trials in
      pediatric and adult populations.

PMID- 16810109
TI  - Effect of baseline- and treatment-related factors on immunologic recovery after
      initiation of antiretroviral therapy in HIV-1-positive subjects: results from
      ACTG 384.
AB  - OBJECTIVE: To assess the effect of baseline- and treatment-related factors on
      immunologic recovery after initiation of antiretroviral therapy (ART). METHODS:
      Nine hundred eighty antiretroviral-naive HIV-1+ subjects were randomized to start
      stavudine/didanosine or zidovudine/lamivudine with nelfinavir, efavirenz, or both
      nelfinavir and efavirenz. RESULTS: Greater CD4 cell recovery was associated with
      age of 40 years or younger, female sex, higher baseline naive/memory CD4 cell
      ratio, higher baseline virus load (VL), and virologic suppression (VS). Most
      subjects who maintained an undetectable VL had a substantial increase in CD4 cell
      count, but 13% of the subjects did not, even after 3 years of VS. Persistent T
      cell activation was associated with lower CD4 cell recovery, even in subjects who
      achieved VS. Initial treatment assignment did not affect total CD4 cell recovery,
      naive/memory CD4 cell reconstitution, or decline in T-cell activation. In
      addition to CD4 cell recovery, B-cell counts rose substantially after ART
      initiation. CONCLUSIONS: In this large randomized trial, younger age, female sex,
      higher naive/memory CD4 cell ratio, higher baseline VL, and VS were associated
      with greater CD4 cell increase, whereas persistent T-cell activation was
      associated with impaired CD4 cell recovery after ART initiation. Initial
      treatment assignment did not affect CD4 cell reconstitution.

PMID- 16810110
TI  - Tissue-specific associations between mitochondrial DNA levels and current
      treatment status in HIV-infected individuals.
AB  - BACKGROUND: Tissue mitochondrial DNA (mtDNA) levels have been proposed as a
      marker of nucleoside analouge reverse transcriptase inhibitor (NRTI) toxicity.
      However, clinical studies have yielded conflicting data regarding possible
      associations with mtDNA levels. This study examined mtDNA levels in matched
      samples of peripheral blood mononuclear cells (PBMCs) and subcutaneous fat from a
      large Australian cohort to examine treatment, clinical, and demographic
      associations with mtDNA depletion. METHODS: mtDNA was quantified by real-time
      polymerase chain reaction. Results were compared across patient treatment and
      demographic details using linear mixed models. RESULTS: One hundred sixty-three
      PBMCs and 161 fat samples were available from 61 individuals. Current NRTI
      exposure was the major determinant of mtDNA levels. Both ddI (didanosine) and d4T
      (stavudine) exposures were associated with mtDNA depletion in fat (P < or =
      0.0001 vs. those not on NRTIs). DdI exposure (P = 0.003), but not d4T exposure (P
      = 0.5), was associated with mtDNA depletion in PBMCs. No association between
      patient demographics or time on current therapy and mtDNA was observed.
      CONCLUSIONS: Current NRTI exposure is the major determinant of tissue mtDNA, but
      the precise determinants are tissue specific. Both ddI and d4T exposure are
      associated with fat mtDNA depletion, whereas ddI exposure was the only observed
      association with mtDNA depletion in PBMCs.

PMID- 16810111
TI  - Visual analog scale of ART adherence: association with 3-day self-report and
      adherence barriers.
AB  - BACKGROUND: Brief self-reports of antiretroviral therapy adherence that place
      minimal burden on patients and clinic staff are promising alternatives to more
      elaborate adherence assessments currently in use. This research assessed the
      association between self-reported adherence on visual analog scale (VASs) and an
      existing, more complex self-reported measure of adherence, the AACTG, and the
      degree to which each method distinguished optimally and suboptimally adherent
      patients in terms of reported barriers to adherence. METHODS: HIV-infected
      patients (N = 147) at a southeastern US clinic completed a computerized
      assessment including an antiretroviral therapy adherence VAS, a modified version
      of the AACTG, and a measure of adherence. RESULTS: Adherence rates were
      comparable across the AACTG (81%) and VAS (87%); they significantly correlated (r
      = 0.585) and produced identical classification of optimal (>90%) or suboptimal
      (<90%) adherence for 66% of patients. In general, VAS scores tended to be higher
      than AACTG scores. Suboptimally adherent patients reported more adherence
      barriers than those classified as optimally adherent, and those so classified by
      the VAS reported considerably more barriers to adherence than those so classified
      by the AACTG. CONCLUSIONS: Results generally support the construct validity of
      the VAS and its use as an easily administered assessment tool that can identify
      patients with barriers to adherence who might benefit from adherence support
      interventions.

PMID- 16810112
TI  - Range of normal neutrophil counts in healthy zimbabwean infants: implications for
      monitoring antiretroviral drug toxicity.
AB  - Mother-to-child HIV prevention trials in sub-Saharan Africa use the US National
      Institutes of Health Division of AIDS (DAIDS) grading scale to monitor
      hematologic toxicity. A recent study of nevirapine prophylaxis given for 6 months
      in breast-feeding Zimbabwean infants reported several cases of relative
      neutropenia in clinically well infants, raising concerns of drug toxicity.
      However, the DAIDS tables are based on normal blood counts for white infants,
      although there is evidence that black African infants may have lower absolute
      neutrophil counts (ANCs) than white infants. To establish normal hematologic
      values in black Zimbabwean infants and to quantify the apparent prevalence of
      relative neutropenia in this population, we evaluated HIV-uninfected healthy
      infants born to HIV-uninfected women at birth, 10 days, 6 weeks, 3, and 4 months
      of life. A physical examination and blood count were performed at each visit, and
      an HIV test was performed at the final visit. The ANC values were graded using
      the DAIDS table. A total of 145 healthy term infants satisfied the inclusion
      criteria. The mean ANC values for Zimbabwean infants were less than half of the
      corresponding standard values at all 5 time points (P < 0.0001). Using the DAIDS
      table in use at the time that the blood was collected, 57% of these healthy
      infants had relative neutropenia of any grade at birth, followed by 29% at day
      10, 53% at 6 weeks, 32% at 3 months, and 37% at 4 months of life. Our data
      indicate that relative neutropenia exists in healthy black Zimbabwean infants.
      The guidelines for identifying toxicity were changed in December 2004. However,
      even by the new DAIDS tables, 43%, 23%, 24%, 42%, and 43% of these healthy babies
      had relative neutropenia at the time of the 5 visits. Future HIV prevention and
      treatment trials in sub-Saharan Africa should use normal hematologic values
      derived from African infants to avoid the overestimation of antiretroviral drug
      toxicity.

PMID- 16810114
TI  - Predictors for lower quality of life in the HAART era among HIV-infected men.
AB  - BACKGROUND: In the era of highly active antiretroviral therapy (HAART),
      maximizing health-related quality of life (QOL) has become a high priority of
      long-term management of HIV-infected individuals. Modifiable determinants of
      lower QOL should be identified for interventions specifically targeted to the
      HAART-using individuals to improve their QOL. OBJECTIVE: To identify the
      predictors for lower QOL among HAART-using study participants in the Multicenter
      AIDS Cohort Study, a longitudinal study of HIV infection among homosexual and
      bisexual men in 4 cities. METHODS: In the Multicenter AIDS Cohort Study, 636
      HAART-using subjects had QOL data before HAART initiation and at least 2
      consecutive QOL measurements after HAART initiation to visit 40 (April 2004).
      Variables of sociodemographics, individual risk behaviors, social support,
      biological markers, HIV-related medication use and clinical outcome indicators
      preceding the study outcomes, the physical health summary score and the mental
      health summary score derived from the standard SF-36 QOL form, were assessed as
      possible predictors using random-effects mixed models. RESULTS: QOL before HAART
      initiation was a strong predictor of QOL subsequent to HAART initiation. Older
      age, lower socioeconomic status, less male sexual partners, no alcohol drinking,
      and more advanced HIV disease stage were significant predictors for lower
      physical health summary score. In addition, more outpatient visits, depression,
      amprenavir use, antiretroviral drug interruption, recreational drug use, and less
      social support were significantly associated with lower mental health summary
      score. DISCUSSION: Many predictors of lower QOL are alterable risk factors that
      can be effectively targeted for interventions to maximize patients' QOL. With
      appropriate treatment and management of HIV disease and depression, clinicians
      can help improve the QOL of their patients. Through modification of individual
      risk behaviors, HIV-infected individuals can enhance their own QOL with support
      from clinicians and the community. In addition, active social support can also be
      an effective way to improve mental health of the infected persons.

PMID- 16810113
TI  - CD4 decline and incidence of opportunistic infections in Cape Town, South Africa:
      implications for prophylaxis and treatment.
AB  - OBJECTIVES: To determine the rate of CD4 decline and the incidence of
      opportunistic infections (OIs) among antiretroviral therapy-naive South African
      HIV-infected patients and inform timing of OI prophylaxis. METHODS: We used mixed
      effect models to estimate CD4 cell decline by CD4 cell count strata in HIV
      infected patients in the Cape Town AIDS Cohort between 1984 and 2000. Stratum
      specific OI incidence per 100 person-years of observation was determined using
      incidence density analysis. RESULTS: Nine hundred seventy-four patients with 2 or
      more CD4 cell counts were included. CD4 counts declined by 47.1 cells/microL per
      year in the stratum with more than 500 cells/microL stratum, 30.6 cells/microL
      per year in the stratum with 351 to 500 cells/microL, and 20.5 cells/microL per
      year in the stratum with 201 to 350 cells/microL. Tuberculosis and oral
      candidiasis were the only OIs that occurred frequently in the stratum with more
      than 200 CD4 cells/microL. Rates of chronic diarrhea, wasting syndrome,
      tuberculosis, and oral and esophageal candidiasis increased in the stratum with
      less than 200 cells/microL, and rates of all OIs were highest in the stratum with
      50 cells/microL or less. CONCLUSIONS: : CD4 cell count declines were dependent on
      CD4 strata and can inform timing of clinic visits and treatment initiation in
      South Africa. Incidence rates of OIs suggest that targeted OI prophylaxis could
      prevent substantial HIV-related morbidity in South Africa.

PMID- 16810115
TI  - Children born to HIV-1-infected women in Sweden in 1982-2003: trends in
      epidemiology and vertical transmission.
AB  - To describe the HIV-1 epidemic among childbearing women and their children in
      Sweden, a population-based analysis of data on all known mother-child pairs in
      Sweden with perinatal exposure to HIV-1 1982-2003 was conducted. The mother-to
      child transmission (MTCT) rate in children prospectively followed from birth
      decreased from 24.7% in 1985-1993 to 5.7% in 1994-1998 and 0.6% in 1999-2003. The
      use of antiretroviral treatment of the mother during pregnancy and/or
      prophylactic antiretroviral intervention increased from 2.3% to 91.6% during the
      same period, and the elective cesarean delivery rate increased from 8.0% to
      80.3%. No MTCT of HIV-1 occurred in Sweden after 1999.Fifty-one vertically HIV-1
      infected children aged 2.7 to 17.6 years were living in Sweden by 31 December
      2003, 71% being treated with antiretroviral agents. No HIV-1-related child death
      has been reported in Sweden after 1996. The conclusion is that MTCT of HIV-1 can
      be almost eliminated when appropriate resources are available. A national
      pregnancy screening program for HIV-1 running since 1987 with a high acceptance
      rate and the implementation of measures to prevent MTCT since 1994 have resulted
      in a significant decrease in the number of infected children. Inasmuch as
      knowledge of the infection status of the mother is crucial for reduction in MTCT
      of HIV-1, continued antenatal screening is important even in a low-prevalence
      country such as Sweden.

PMID- 16810116
TI  - HIV seroincidence estimates among at-risk populations in Buenos Aires and
      Montevideo: use of the serologic testing algorithm for recent HIV seroconversion.
AB  - Using the serological testing algorithm for recent HIV seroconversion, we
      estimated annualized incidences (per 100 person-years) of HIV-1 infection in
      different at-risk groups in Buenos Aires and Montevideo, during a 5-year period
      between 1998 and 2003. HIV-positive serum samples from 9 serosurveys conducted
      among men who have sex with men, patients attending clinics for a sexually
      transmitted infections consult (STIs), female commercial sex workers, injecting
      drug users (IDUs), noninjecting cocaine users (NICUs), asymptomatic women
      screened for HIV infection, and patients with tuberculosis were used. HIV
      incidences were as follows: 6.7 for men who have sex with men, 2.0 for STIs, 1.3
      for female commercial sex workers, 0.0 for Argentinean IDUs, 10.3 for Uruguayan
      IDUs, 3.1 for Argentinean NICUs, 4.4 for Uruguayan NICUs, and 2.4 for patients
      with tuberculosis. Among asymptomatic women screened for HIV infection, incidence
      rose from 0.4 in 1998 to 4.6 in 1999 and to a high of 10.2 in the year 2000.
      Unexpectedly, high HIV incidences were detected among at-risk groups in Buenos
      Aires and Montevideo. This pattern shows an emerging HIV epidemic among
      heterosexuals stemming from core HIV-infected at-risk groups. There is an urgent
      need for development and implementation of specific prevention strategies to
      address this burgeoning epidemic.

PMID- 16810117
TI  - Delayed sample processing leads to marked decreases in measured plasma IL-7
      levels.

PMID- 16810118
TI  - Polymorphism of the protease and reverse transcriptase and drug resistance
      mutation patterns of HIV-1 subtype B prevailing in China.

PMID- 16810119
TI  - Comparison of HIV-1 mother-to-child transmission after single-dose nevirapine
      prophylaxis among African women with subtypes A, C, and D.

PMID- 16810120
TI  - Patient-delivered partner treatment and other partner management strategies for
      sexually transmitted diseases used by New York City healthcare providers.
AB  - OBJECTIVES: The objectives of this study were to measure frequency and predictors
      of patient-delivered partner treatment (PDPT) and the frequency of other partner
      management strategies among New York City healthcare providers (HCPs) as well as
      to determine whether use of PDPT detracts from other partner management
      strategies. STUDY DESIGN: The authors conducted a cross-sectional survey of New
      York City HCPs. RESULTS: Frequent patient referral was reported by 93.6% (368 of
      393) of healthcare providers; only 20% (80 of 401) reported frequent use of
      provider referral. Overall, 49.2% (196 of 398) of HCPs reported ever using PDPT
      and 27.1% (108 of 398) reported using PDPT frequently. HCP specialty, practice
      setting, duration of practice, report of frequent provider referral practice, and
      HCP race/ethnicity were the strongest predictors of PDPT use. HCPs reporting PDPT
      use were more likely to report frequent provider referral than those who had
      never used PDPT (26.7% vs. 12.6%; P <0.001). CONCLUSIONS: PDPT use is common and
      is being used in conjunction with other partner management strategies.

PMID- 16810122
TI  - CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral
      load in HIV-infected children on highly active antiretroviral therapy.
AB  - OBJECTIVE: The aim of this study was to analyze the association between CD4(+)
      depletion and immune activation in HIV-1-infected children on highly active
      antiretroviral therapy (HAART). DESIGN AND SETTING: We carried out a cross
      sectional study to determine the profile of several immunologic parameters in 143
      children on HAART for more than 24 weeks. Children were stratified according to
      current immunologic status (CD4 < or =15%, 15%-25%, and > or =25%) and viral load
      (VL) levels (<400 copies/mL; 400-10,000 copies/mL; and >10,000 copies/mL). We
      also studied 23 uninfected children as healthy controls. METHODS: Viral load (HIV
      RNA copies per milliliter) was quantified using reverse transcriptase polymerase
      chain reaction molecular assay. T-cell subsets were determined by multiparametric
      flow cytometry. RESULTS: HIV-infected children with low percentage of CD4(+) had
      high memory (CD45RO(+)) and low naive (CD45RA(+)) CD4(+) and CD8(+) T-cell
      values. Furthermore, children with CD4(+) >25% had similar memory and naive
      CD4(+) values as the healthy control group, whereas memory and naive CD8(+)
      subsets were different from the healthy control values. In these HIV-infected
      children, when CD4(+) was depleted, the amount of naive plus central memory
      CD8(+) (CD28(+)CD57(-)) cells was decreased, whereas effector CD8(+) (CD28(
      )CD57(+)) cells were upregulated, and these values were always higher than
      healthy control values. Furthermore, children with low percentage of CD4(+)
      showed significant upregulation of HLA-DR(+)CD38(+) and HLA-DR(+) in both CD4(+)
      and CD8(+) T-cells independent of VL levels. CONCLUSIONS: Our data suggest that
      elevated immune activation could be responsible for CD4(+) depletion rather than
      HIV replication because immunologic status is associated directly to immune
      activation and not to VL levels in HIV-infected children on HAART.

PMID- 16810121
TI  - Men who have sex with men: perceptions about sexual risk, HIV and sexually
      transmitted disease testing, and provider communication.
AB  - OBJECTIVES: This study was designed to gain a deeper understanding of the
      barriers and facilitators related to sexually transmitted diseases (STDs) and HIV
      screening among at-risk Boston men who have sex with men (MSM). STUDY DESIGN: The
      cohort was recruited by a modified respondent-driven sampling technique and used
      one-on-one semistructured interviews and a quantitative survey to examine
      participants' understanding of STDs and HIV, perceptions of risk for disease,
      reasons for getting (or not getting) tested, and experiences with testing.
      RESULTS: The study found that although most of the MSM knew the signs and
      symptoms of HIV, they were less familiar with STDs. MSM were most likely to be
      screened if they had symptoms or were told by a partner of a recent exposure.
      However, many barriers to STD/HIV screening among MSM still exist, including lack
      of awareness of symptoms, misperceptions about the ways STDs are transmitted, and
      perceived impediments from the healthcare system, including misgivings about
      provider sensitivity. CONCLUSIONS: To decrease current increases in HIV/STDs
      among MSM, new strategies that include community and provider education are
      needed.

PMID- 16810123
TI  - Regulatory dysfunction of the interleukin-7 receptor in CD4 and CD8 lymphocytes
      from HIV-infected patients--effects of antiretroviral therapy.
AB  - Despite an increase in plasma IL-7 levels, the CD4 T-cell pool decrease
      progressively in HIV-infected patients. Here we report on our tests to check the
      hypothesis that defects in the IL-7 receptor system might be involved in this
      phenomenon. The cell surface expression of CD127 was measured ex vivo in CD4 and
      CD8 T lymphocytes drawn from 3 groups of HIV patients. IL-7 function was also
      followed in vitro by measuring IL-7-driven T-cell proliferation, the induction of
      the CD25 activation marker, and overexpression of the antiapoptotic molecule Bcl
      2. Untreated viremic patients showed a slight but significant decrease in CD127
      expression on the surface of their CD4 lymphocytes. By contrast, CD127 expression
      was substantially altered on the surface of CD8 T lymphocytes taken from
      untreated viremic patients. IL-7-induced overexpression of the antiapoptotic
      molecule Bcl-2 was dramatically altered in viremic patients, whereas IL-7
      dependent CD25 induction and T-cell proliferation were reduced. Highly active
      antiretroviral therapy partially corrected these defects in patients with an
      undetectable viral load and CD4 counts of more than 400 cells/microL. The effects
      of HAART were less pronounced in patients with undetectable VL but low CD4 counts
      (<250 cells/microL). The IL-7 receptor is dysfunctional in the CD4 and CD8
      lymphocytes of HIV-infected patients. This may be due to abnormal activation of
      the immune system in HIV-infected patients and may contribute to the reduced CD4
      count and the altered function of the CD8 compartment.

PMID- 16810124
TI  - Feasibility and effectiveness of cotrimoxazole prophylaxis for HIV-1-infected
      adults attending an HIV/AIDS clinic in Uganda.
AB  - BACKGROUND: Cotrimoxazole is recommended for prevention of opportunistic
      infections in symptomatic HIV patients in sub-Saharan Africa. METHODS: We
      examined the feasibility and effectiveness of daily cotrimoxazole prophylaxis in
      a well-established cohort of HIV-infected adults attending clinics in Entebbe,
      Uganda. We compared mortality and morbidity rates for 12 months before and after
      the introduction of cotrimoxazole. RESULTS: Between August 2000 and February
      2002, 94% of cohort members were enrolled onto cotrimoxazole prophylaxis.
      Revisits were scheduled every 4 weeks to replenish pills; patients attended 61%
      of revisits. The main reasons for nonenrollment and defaulting were lack of
      transport, being away from home, and sickness. Drug-related adverse events,
      mainly itching and rash, were seen in 4% of participants. Although bacterial
      resistance rate to cotrimoxazole was high, the adjusted mortality incidence rate
      ratio was significantly reduced after the introduction of cotrimoxazole (0.76;
      95% confidence interval, 0.60-0.96; P = 0.020). Overall febrile events and
      morbidity rates were unchanged after the introduction of cotrimoxazole, but the
      incidence of malaria was reduced (incidence rate ratio, 0.31; 95% confidence
      interval, 0.13-0.72). CONCLUSIONS: Cotrimoxazole prophylaxis can be introduced
      into routine HIV clinic activities and is associated with a reduction in overall
      mortality and malaria morbidity, even in an area with high bacterial resistance.
      These results reinforce the need for large-scale provision of cotrimoxazole
      prophylaxis for all HIV-positive patients in developing countries.

PMID- 16810125
TI  - Intensive pharmacokinetics of zidovudine 200 mg twice daily in HIV-1-infected
      patients weighing less than 60 kg on highly active antiretroviral therapy.

PMID- 16810127
TI  - Plasma HDL subfraction levels increase in rats fed proso-millet protein
      concentrate.
AB  - BACKGROUND: Millet has been consumed as human food in the countries of Asia and
      Africa. We reported previously the effects of dietary protein concentrates from
      proso millet (Panicum miliaceum L.) on plasma levels of high-density lipoprotein
      HDL cholesterol. Of note is that of these HDL subfractions, HDL2 particles may
      have the more strongly protective effect against the risk of coronary heart
      disease than HDL3. However, it is unclear how dietary millet protein affects
      plasma levels of HDL subfractions. MATERIAL/METHODS: We examined the effect of
      feeding of proso-millet protein concentrate (PMPC) for 21 days on plasma levels
      of HDL cholesterol, HDL subfractions and lecithin: cholesterol acyltransferase
      (LCAT) activities in rats. RESULTS: Results showed a clear elevation of plasma
      levels of HDL cholesterol (p<0.05) without an increase in low density lipoprotein
      cholesterol levels and enhancement of LCAT activities (p<0.06) by the intake of a
      PMPC diet compared with a casein diet. This increase in HDL cholesterol levels
      was substantially due to the elevation of HDL2 subfractions (p<0.05).
      CONCLUSIONS: PMPC could have a beneficial effect on cardiovascular disease
      because HDL2 subfractions may have the more strongly protective effect against
      the risk of coronary heart disease.

PMID- 16810128
TI  - Up-regulation of p21WAF1 expression is mediated by Sp1/Sp3 transcription factors
      in TGFbeta1-arrested malignant B cells.
AB  - BACKGROUND: TGFbeta1 has a profound effect on the growth of various mammalian
      cell types, including B lymphocytes. The inhibitory action of TGFbeta1 is
      mediated by deactivation of the cell cycle machinery. Several feedback-sensitive
      pathways determine whether the cells are stopped in G1 phase or allowed to leave
      G1 phase and enter S phase. Cell cycle-associated molecules, e.g. cyclin
      dependent kinase inhibitors (CKIs), may become targets for the inhibitory
      signaling pathways induced by TGFbeta1. MATERIAL/METHODS: Our experimental DoHH2
      cell line model was derived from a patient with malignant non-Hodgkin's lymphoma
      of follicular origin. The effect of TGFbeta1 on cell cycle progression was
      studied by flow cytometry. We examined the effect of TGFbeta1 on the expression
      of p21WAF1 by immunoblotting and RT-PCR. The binding activity of transcription
      factors to the p21 gene promoter was determined by gel mobility shift assay
      (GMSA). RESULTS: Our results showed that TGFbeta1 treatment increased the number
      of cells arrested in G0/G1 phase compared with untreated control cells. Moreover,
      we found that p21WAF1 expression was significantly up-regulated on the protein
      level after TGFbeta1 treatment. Similarly to the protein level, the expression of
      p21 mRNA was increased in TGFbeta1-treated cells. We further examined the binding
      activity of the Sp family of transcription factors to examine their role in
      p21WAF1 up-regulation. CONCLUSIONS: The results indicated that p21WAF1 over
      expression in TGFbeta1-arrested malignant B cells is mediated by binding of
      Sp1/Sp3 transcription factors to the (-92/-71), (-77/-58), and (-65/-45) elements
      of the promoter region of the p21 gene.

PMID- 16810129
TI  - Evaluation of the BacT/ALERT and BACTEC 9240 automated blood culture systems for
      growth time of Brucella species in a Turkish tertiary hospital.
AB  - BACKGROUND: The isolation of Brucella species from blood may be achieved by using
      classic culture techniques, but detection of the organism is difficult due to its
      slow growth. The time-to-detection of Brucella can take up to 30 days using the
      Castaneda blood culture method. Automated blood culture systems have reduced the
      growth time of Brucella. MATERIAL/METHODS: In this report we would like to
      contribute our experience on detection time in the isolation of Brucella species
      from 33,039 blood culture sets using BacT/ALERT between 1995 and 2000 (13
      isolates) and thereafter using both the BACTEC and BacT/ALERT systems (17
      isolates). RESULTS: Thirty Brucella spp. (17 by both systems and 13 by BacT/ALERT
      only) were isolated from 33,039 blood culture sets between 1995 and 2002.
      Brucellae were recovered between 1.8 and 3.7 days (mean: 2.5 days) in the
      BacT/ALERT blood culture system and between 2.1 and 3.8 days (mean: 2.8 days) in
      BACTEC 9240 system. CONCLUSIONS: We concluded that the mean time-to-detection
      could be <or=3 days, which is considered rapid enough for starting appropriate
      evidence-based treatment in an endemic setting.

PMID- 16810130
TI  - Androgen binding site in J111 cell line.
AB  - BACKGROUND: The finding of sex steroid receptor protein in non classical
      reproductive tissues suggested the possibility that sex steroids may have a
      relevance to the immune system. MATERIAL/METHODS: The J111 cells were maintained
      in RPMI 1640 complete medium at 37 degrees C in 5% CO2 in air. Cells were
      resuspended at 1x10(6) cells in 0.2 ml complete medium in 1.5 ml eppendorf tubes.
      A single saturating concentration 1x10(-9) M of [3H]5alpha-DHT was added to the
      cells suspension. Unlabelled steroids (5alpha-DHT, 17-beta estradiol, or the
      synthetic glucocorticoid triamcinolone acetonid) were added over the range 1x10(
      8) to 1x10(-9) M. Duplicate tubes were incubated at 37 degrees C for 1h. For
      autoradiography, the supernatant was discarded and the pellet resuspended in 0.2
      ml medium. For binding assay, Labeled cells were separated from unbound steroid
      by immunomagnetic bead using anti-CD68 antibody. RESULTS: In autoradiography, a
      population of approximately 96% of J111 cells that contain receptors for androgen
      has been demonstrated. The results of immunomagnetic showed that binding
      identified in the J111 cells was modest selective towards androgenic compounds.
      Schatchard analysis of data showed the KD value of 2.5x10(-9) M and the number of
      receptor in each cell was found to be 257+/-1. Little competition was seen from
      17 beta estradiol or the synthetic glucocorticoid triamcinolone acetonid.
      CONCLUSIONS: These data indicate that androgen binding in J111 cells is of modest
      affinity and specific, due to the inability of 100-fold molar excess of estradiol
      to displace bound [3H]-5alphaDHT.

PMID- 16810131
TI  - Activated Leukocyte Cell Adhesion Molecule (ALCAM) is associated with suppression
      of breast cancer cells invasion.
AB  - BACKGROUND: Activated Leukocyte Cell Adhesion Molecule (ALCAM) is expressed in
      different kinds of normal and neoplastic tissues. Data on the tissue distribution
      of ALCAM suggest that this protein is involved in tumor progression and
      metastasis. The lack of available data on ALCAM protein expression in breast
      cancer prompted us to undertake a study on the involvement of this adhesion
      molecule in tumor development. MATERIAL/METHODS: The expressions of ALCAM and
      reference biomarkers were examined in 56 breast cancer specimens by laser
      scanning cytometry and confocal microscopy. The results were related to clinical
      and pathological parameters, i.e. histological grade, tumor diameter, lymph node
      involvement, NPI, steroid receptor (estrogen, ER, and progesterone, PgR)
      expression, and HER2/neu over-expression. RESULTS: High levels of ALCAM
      significantly correlated with small tumor diameter (p=0.009), low tumor grade
      (p=0.001), and the presence of progesterone (p=0.009) and estrogen (p=0.006)
      receptors. Declining ALCAM concentrations correlated with HER2/neu gene
      amplification, inasmuch as the obtained p value, 0.065, was very close to the
      established statistical significance level of p=0.05. The ALCAM/MMP-2 ratio was
      significantly higher in cancer cases characterized by small tumor size (p=0.04)
      and low tumor grade (p=0.022). CONCLUSIONS: Analysis of ALCAM expression in
      relation to other molecular biomarkers revealed that ALCAM expression and the
      ALCAM/MMP-2 ratio are more promising indicators of breast cancer progression than
      MMP-2, E-cadherin, and alpha-catenin. Low ALCAM concentration correlated with an
      aggressive tumor phenotype, which supports the view that this adhesion molecule
      is a tumor suppressor marker with prognostic significance.

PMID- 16810132
TI  - Correlation between gait and balance in people with and without Type 2 diabetes
      in normal and subdued light.
AB  - BACKGROUND: Balance and gait are both impaired in people with diabetes but no
      study has examined both in the same subjects in people either with or even
      without diabetes or related these to room lighting. MATERIAL/METHODS: Twelve
      subjects with type 2 diabetes (D) and 15 age-matched controls (C) were examined
      under conditions of full light, eyes closed (no light) and low light (5 candle
      power). Balance was assessed during standing by a computerized posturography
      device. Gait was analyzed during the initiation of movement, while walking at
      uniform speed and during turns of 0.66 meters diameter through accelerometers,
      foot contact sensors and the electomyogram recorded from the gastrocnemius and
      tibialus anterior muscles. RESULTS: Subjects with diabetes had poorer balance
      during standing in diminished light compared to full light and no light
      conditions. When the room light was dimmed, sway during standing increased by an
      average of 25% in D. Control subjects did not have different sway with diminished
      light compared to the other lighting conditions. Gait was slower, circumduction
      greater and muscle use greater in D than C. There was a significant negative
      correlation between balance and gait; the worse the balance, the slower and
      poorer the gait for both groups of subjects (p<0.05), impaired balance accounting
      for 70% of the deviation in gait in D whereas it only accounted for 52% in C.
      CONCLUSIONS: Balance and gait are related in people with and without diabetes.
      Diabetes causes balance and gait to both be impaired compared to C.

PMID- 16810133
TI  - Female fibromyalgia patients: lower resting metabolic rates than matched healthy
      controls.
AB  - BACKGROUND: Many features of fibromyalgia and hypothyroidism are virtually the
      same, and thyroid hormone treatment trials have reduced or eliminated
      fibromyalgia symptoms. These findings led the authors to test the hypothesis that
      fibromyalgia patients are hypometabolic compared to matched controls.
      MATERIAL/METHODS: Resting metabolic rate (RMR) was measured by indirect
      calorimetry and body composition by bioelectrical impedance for 15 fibromyalgia
      patients and 15 healthy matched controls. Measured resting metabolic rate (mRMR)
      was compared to percentages of predicted RMR (pRMR) by fat-free weight (FFW)
      (Sterling-Passmore: SP) and by sex, age, height, and weight (Harris-Benedict:
      HB). RESULTS: Patients had a lower mRMR (4,306.31+/-1077.66 kJ vs 5,411.59+/
      695.95 kJ, p=0.0028) and lower percentages of pRMRs (SP: -28.42+/-15.82% vs 
      6.83+/-12.55%, p<0.0001. HB: -29.20+/-17.43% vs -9.13+/-9.51%, p=0.0008). Whereas
      FFW, age, weight, and body mass index (BMI) best accounted for variability in
      controls' RMRs, age and fat weight (FW) did for patients. In the patient group,
      TSH level accounted for 28% of the variance in pain distribution, and free T3
      (FT3) accounted for 30% of the variance in pressure-pain threshold. CONCLUSIONS:
      Patients had lower mRMR and percentages of pRMRs. The lower RMRs were not due to
      calorie restriction or low FFW. Patients' normal FFW argues against low physical
      activity as the mechanism. TSH, FT4, and FT3 levels did not correlate with RMRs
      in either group. This does not rule out inadequate thyroid hormone regulation
      because studies show these laboratory values do not reliably predict RMR.

PMID- 16810134
TI  - The influence of alterations in room temperature on skin blood flow during
      contrast baths in patients with diabetes.
AB  - BACKGROUND: Contrast baths (CB) have been used for over two thousand years. But
      it only was recently that CB were shown to improve limb circulation to a greater
      extent than that which can be seen after continuous exposure to a warm, constant
      temperature, bath. However, other studies show that this type of response to
      temperature can be impaired if the sympathetic nervous system applies
      vasoconstriction to the blood vessels. Therefore the purpose of the present
      investigation was to examine the relationship between sympathetic outflow on the
      magnitude of the change of blood flow (BF) during contrast baths in controls and
      with people diabetes. Sympathetic vasoconstriction activity was altered by global
      heating. MATERIAL/METHODS: Fourteen patients with type 2 diabetes were compared
      to 14 age-matched controls. BF was measured during 16 minutes of serial contrast
      baths of the foot following 3 minutes of warm water and 1 min of cold immersion
      at 2 different room temperatures, 19 and 32 deg C. RESULTS: When subjects were
      exposed to global heating (warm room) there is a greater response to CB than when
      subjects were initially in a cooler room. However, for both temperatures,
      subjects with diabetes had a response that was over 50% less than that seen in
      control subjects. CONCLUSIONS: Removing sympathetic vasoconstrictor tone by
      global heating benefits subjects with diabetes and control subjects in their
      response to CB. For subjects with diabetes, global heating may be necessary to
      increase blood flow to acceptable levels for effective therapy.

PMID- 16810135
TI  - Outcome and prognosis of severe thrombotic microangiopathies treated by plasma
      exchange.
AB  - BACKGROUND: Plasma exchange (PE) therapy has dramatically improved the outcome of
      thrombotic microangiopathies (TMA) in adults. However, resistance to PE, which
      indicates a poor prognosis, is observed in 1/3 of patients and remains not fully
      understood. We evaluated in this study the survival and the long-term outcome of
      severe TMA treated by PE and identified the predictive factors of resistance to
      PE and of mortality. MATERIAL/METHODS: Records of adults with severe TMA treated
      by PE were reviewed. Clinical and biological data, therapeutic delay to PE,
      plasma volume exchange per procedure, and number of PE sessions were collected.
      Mortality was assessed at one month and at one-year follow-up. All data were
      analyzed and compared between survived/deceased and between responder/non
      responder patients. RESULTS: Nineteen females and six males were included. Mean
      age (+/-SD) was 46.8+/-16.3 years, Glasgow coma score 11+/-3, and Sequential
      Organ Failure Assessment (SOFA) score 5.8+/-2.8. Nineteen patients partially or
      fully responded to PE. Twenty patients were alive at one month and 19 at one
      year. The response to PE was the single discriminating parameter between
      survivors and non-survivors. A longer delay of PE and a neoplastic cause of TMA
      were significantly higher in the non-responders. CONCLUSIONS: Severe TMA treated
      by PE had a fair prognosis, with a survival rate at 76% after one year of follow
      up. Unresponsiveness to PE was the only predictive factor of mortality; a
      neoplastic etiology of TMA and a longer therapeutic delay of PE were predictive
      of resistance to PE.

PMID- 16810136
TI  - Long-term follow-up of mitral valve repair: a single-center experience.
AB  - BACKGROUND: Our aim was to conduct a long-term follow-up of patients after mitral
      valve repair for incompetence. We identified determinants for mortality and
      compared mortality with standardized mortality rates of the Dutch population.
      MATERIAL/METHODS: We included in this single-center retrospective study 119
      patients operated from March 1976 to February 1981. Patients with previous mitral
      valve surgery, isolated mitral stenosis, and congenital heart disease were
      excluded. Routine echocardiography was performed every 6 to 12 months. The
      cumulative probability of survival was calculated (Kaplan-Meier). The variables
      that statistically significantly associated with mortality were selected for
      multivariate analysis. Maximum follow-up was 27 years and complete in 98%. Mean
      age was 49.4 years, and 55% were preoperatively in New York Heart Association
      (NYHA) class III. Concomitant cardiac procedures were performed in 49%. RESULTS:
      The 30-day postoperative mortality was 6.7% and the 20-year overall mortality was
      63%. The standardized mortality rate was 30%, which was based on survival rates
      of the general Dutch population. In 27 cases (22.7%), re-operation was performed.
      Independent predictors for mortality were, after univariate and multivariate
      analysis, concomitant coronary artery bypass grafting (p=0.002), renal impairment
      (p=0.027), age above 60 years (p=0.05), and ejection fraction<or=40% (p=0.05).
      CONCLUSIONS: The observed mortality exceeded the expected mortality. Concomitant
      coronary artery bypass grafting, renal impairment, age above 60 years, and
      reduced left ventricular function were independent predictors of mortality in
      patients with surgical repair for mitral valve regurgitation.

PMID- 16810137
TI  - Typical pulmonary carcinoid tumors: presentation and outcome of 24 cases.
AB  - BACKGROUND: The aim of the study was to determine the presenting clinical
      radiological features and outcomes of typical pulmonary carcinoid tumors in our
      center. MATERIAL/METHODS: The medical records of 24 patients with typical
      pulmonary carcinoid tumor diagnosed between January 1995 and December 2003 were
      retrospectively reviewed. Follow-up information on patients was obtained from
      direct patient contact in February 2004. RESULTS: There were 17 female and 7 male
      patients with a mean age of 40.3 years (range: 17-69 years). Sixteen patients
      (66.7%) were nonsmokers. The most frequent presenting symptom was cough, followed
      by hemoptysis. Twenty-three patients had an abnormal chest X-ray, showing
      atelectasis in seven. Bronchoscopy revealed mass lesion in all cases. In 13
      cases, tumor was located in the lobar bronchi. Diagnosis of carcinoid tumor was
      established with bronchoscopy in 19 patients and with thoracotomy in five cases.
      While surgery was the treatment modality in 23 patients, one patient refused
      treatment. Lobectomy was performed in 15 cases and six of them were sleeve
      lobectomy. One patient died two days after operation due to ischemic heart
      disease, two were lost to follow-up, and 21 patients were still alive. Survival
      for the 21 patients was between 5 and 96 months. Eight patients had survival of
      more than five years. CONCLUSIONS: Our data suggest that typical pulmonary
      carcinoids are different from major lung cancer types with respect to sex, age
      predilection, and smoking history. Surgery is the treatment of choice for
      pulmonary carcinoid tumors. These patients had excellent prognosis after surgical
      treatment.

PMID- 16810138
TI  - Effects of a symptom control intervention on utilization of health care services
      among cancer patients.
AB  - BACKGROUND: In this study we investigated the effects of a clinical nursing
      symptom control intervention on utilization of physician, hospital and emergency
      room services. MATERIAL/METHODS: Two hundred twenty-two patients currently
      undergoing chemotherapy were recruited for the study, and were randomized into
      either the 10-contact, 20-week experimental intervention group (110), where the
      intervention focused on assisting the patient in managing their symptoms, or to a
      conventional care control group (112). RESULTS: A random effects regression model
      revealed that patients in the intervention group reported fewer emergency room
      visits than patients in the control group (p=0.050). Greater symptom severity and
      more comorbid conditions were also predictive of more emergency room visits. The
      intervention was effective in reducing the number of hospital visits for the
      subgroup of patients who at baseline reported above average symptom severity
      (p=0.023). CONCLUSIONS: These findings suggest that a nursing intervention
      focusing on educating patients regarding specific strategies to be applied for
      controlling symptoms may be worthwhile, as the patients may regain some control
      in managing their symptoms and thus ultimately require fewer emergency room
      services and hospital visits. Such a straightforward approach may empower
      patients, enhance their quality of life and reduce overall costs of cancer care.

PMID- 16810139
TI  - Primary cutaneous malignant fibrous histiocytoma: a case report.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) is one of the commonest soft
      tissue sarcomas to occur in the extremities, but presentation as a primary
      cutaneous lesion is rare. MFH can present as a cutaneous lesion in the form of a
      primary tumor or as metastasis from MFH at other sites, such as primary MFH of
      the breast; however, both presentations are very rare. CASE REPORT: We report
      here a 55-year-old male patient with cutaneous MFH on the right thigh region. The
      patient presented with two swellings on the outer aspect of the thigh of three
      months' duration, which ulcerated following the first month. The swellings were
      non-tender, soft, compressible, and not fixed to underlying structures.
      Histopathologic examination of the excised tumor revealed highly pleomorphic
      spindle-shaped cells arranged in sheets and irregular fascicles with a focal
      storiform pattern. Many thin-walled blood vessels and focal inflammatory cell
      infiltration with occasional focus of myxoid change was seen. Storiform
      pleomorphic type of MFH grade II was diagnosed. Wide local excision was done. The
      patient made an uneventful recovery. CONCLUSIONS: Although MFH is one of the
      commonest soft tissue sarcomas, cutaneous presentation is very rare. A high index
      of suspicion is necessary to keep this possibility in mind, as it can present in
      different forms, including the pedunculated types, which can be compressible. MFH
      variants such as atypical fibrous histiocytoma or atypical fibroxanthoma can
      occur sometimes as cutaneous MFH. Wide local excision is commonly possible in
      most of the cases for therapy.

PMID- 16810140
TI  - Incarcerated Spigelian hernia: a case report.
AB  - BACKGROUND: Spigelian hernia is a rare partial abdominal wall defect in the
      transversus abdominus aponeurosis or Spigelian fascia. We here report the case of
      a patient with incarcerated greater omentum in a Spigelian hernia. CASE REPORT:
      The patient presented with a six-hour history of nausea, constant abdominal pain,
      and a palpable mass in the left lower quadrant. Abdominal computed tomography
      revealed that omentum was strangulated in a Spigelian hernia that was
      successfully treated by plug and mesh repair. No recurrence has been observed
      during three-year follow-up. CONCLUSIONS: In our case, plug and mesh repair was a
      safe and effective method of repairing an incarcerated Spigelian hernia with
      durability through three years of follow-up.

PMID- 16810141
TI  - Evaluating a new method for maintaining body temperature during OPCAB and robotic
      procedures.
AB  - BACKGROUND: We evaluated the performance of a new temperature management system
      (Allon Thermowrap, MTRE, Israel) in maintaining normothermia during OPCAB (Off
      Pump Coronary Artery Bypass) procedures and Zeus-robotic IMA (internal mammary
      artery) takedowns. MATERIAL/METHODS: One hundred patients were prospectively
      randomized to either a conventional temperature management method (thick blanket,
      warm intravenous fluids, operating room temperature 25 degrees C), or the new
      Allon Thermowrap system (pads with temperature-controlled water circulation
      placed on the patient's back, legs, and arms). The mean age, body surface area,
      total operating time, and OR air temperature were similar in both groups.
      RESULTS: The Allon Thermowrap system maintained a higher bladder and
      nasopharyngeal temperature (p<0.05). The SVR decreased (p<0.05) and the cardiac
      index increased (p<0.05) in patients with a body temperature>35.80 degrees C.
      Without reaching a significant level, the postoperative blood loss was lower in
      the Allon Thermowrap group. CONCLUSIONS: The Allon Thermowrap system
      significantly out-performed conventional techniques in achieving and maintaining
      normothermia during off-pump and robotic procedures.

PMID- 16810142
TI  - Screening for human papillomavirus (HPV) in Egyptian women by the second
      generation hybrid capture (HC II) test.
AB  - BACKGROUND: HPV infection is the main cause of cervical cancer and cervical
      intraepithelial neoplasia worldwide. The second-generation HC II test is a liquid
      hybridization assay designed to detect 18 HPV types. The aim of the present study
      was to detect the rate of HPV infection and its various genotypes among Egyptian
      women. MATERIAL/METHODS: We evaluated 166 Egyptian women. They were classified
      according to cytology into those with normal cytology, chronic nonspecific
      cervicitis, and squamous intraepithelial lesions (SILs). RESULTS: The overall
      prevalence of HPV DNA in the studied groups was 15.06% (25/166). Among the 25 HPV
      positive women, 16 (64%) were infected with high-risk HPV types, 4 (16%) with low
      risk HPV types, while 5 (20%) had both types. Twenty-one (84%) of the infected
      women harbored at least one high-risk HPV type, while 9 (36%) harbored at least
      one low-risk HPV type. Values of HPV viral load for low-risk HPV infection showed
      no significant difference in the normal and chronic nonspecific cervicitis
      groups. But when HPV viral load of high-risk HPV infection was compared in the
      normal, chronic nonspecific cervicitis, and SIL groups, a significant difference
      was found. The same was detected between chronic nonspecific cervicitis and SIL
      and between normal cytology and SIL, suggesting an association between viral load
      and risk of SIL and, accordingly, cancer. CONCLUSIONS: It may be concluded that
      HPV testing using the HC II assay is a useful tool when combined with cytology in
      the diagnosis of high-risk HPV viral types in apparently normal tissues.

PMID- 16810143
TI  - Lymphotoxin-alpha and cardiovascular disease: clinical association and pathogenic
      mechanisms.
AB  - Inflammation plays an important role in atherosclerotic plaque formation, rupture
      and thrombogenicity. Many cytokines are the most important biomediates of
      inflammation and its associated vascular lesions. Lymphotoxin-alpha (LTalpha) is
      part of the tumor necrosis factor (TNF) family of cytokines that mediates an
      inflammatory or immunologic response that can affect cell death or
      differentiation, and provide an important link of communication between
      lymphocytes and stromal cells. Several genetic and clinical studies implicate
      LTalpha, and its binding and regulatory partner galectin-2, as a risk factor in
      the pathogenesis of cardiovascular diseases including miocardial infarction,
      aortic aneurysm, and cerebral infarction. The LTalpha gene variability is also
      associated with an increased level of C-reactive protein, an inflammatory marker.
      In knockout mice, loss of LTalpha leads to a reduction of atherosclerotic lesion
      size. Together, these findings support the cytokine LTalpha as a mediator of
      inflammation and its association with the pathogenesis of cardiovascular disease.
      However, the molecular mechanisms of LTalpha -induced cellular responses are
      largely unknown. Preliminary studies indicate that the combination of LTalpha
      subunits, specific interaction with its potential receptors and other cytokines,
      and signal transduction pathways may significantly contribute to the overall
      effects of LTalpha on the inflammation, gene expression, and functions of
      cardiovascular cells. More clinical and basic science studies are warranted to
      further understand the role of LTalpha in cardiovascular disease.

PMID- 16810144
TI  - Small RNAs and development.
AB  - Small RNAs, including microRNAs (miRNAs), short interfering RNAs (siRNAs), and
      siRNA-like scan RNAs (scnRNAs), are known to be crucial for regulatory functions
      in diverse species, with special focus on their interference in the development
      of plants as well as of C. elegans, Drosophila, and other animals. The functions
      of small RNAs on the complex regulatory network of metazoan embryonic development
      are presented in this article. In addition, indirect evidence is summarized here
      for those miRNAs which are important regulators controlling the biological
      processes of germ-cell development.

PMID- 16810145
TI  - Diabetes mellitus: complications and therapeutics.
AB  - Diabetes mellitus has now assumed epidemic proportions in many countries of the
      world. With the present population of 19.4 million diabetics, and approximately
      60 million by the year 2025, India would rank first in its share of the global
      burden of diabetes. Diabetes mellitus is characterized by derangement in
      carbohydrate, protein, and fat metabolism caused by complete or relative
      insufficiency of insulin secretion and/or insulin action. There are two main
      forms of diabetes, type 1 (insulin-dependent diabetes mellitus) and type 2 (non
      insulin-dependent diabetes mellitus). Insulin sensitizers (thiazolidinediones),
      new-generation insulin secretagogue (glimepiride), acarbose, and designer insulin
      (lispro and aspart) have enormously helped in achieving better metabolic control.
      Despite the great strides that have been made in the understanding and management
      of type 2 diabetes, insulin resistance and diabetes-related complications are
      increasing unabated. The present review not only updates our knowledge in
      delineating the molecular mechanism(s) causal to insulin sensitivity or
      resistance, but also provides clues for the prognosis of diabetes and its better
      management.

PMID- 16810146
TI  - Eastern equine encephalitis--New Hampshire and Massachusetts, August-September
      2005.
AB  - During August-September 2005, the New Hampshire Department of Health and Human
      Services reported seven cases of human eastern equine encephalitis virus (EEEV)
      disease, the first laboratory-confirmed, locally acquired cases of human EEEV
      disease reported from New Hampshire in 41 years of national surveillance. Also
      during August--September 2005, the Massachusetts Department of Public Health
      reported four cases of human EEEV disease, five times the annual average of 0.8
      cases reported from Massachusetts during the preceding 10 years. Four of the 11
      patients from New Hampshire and Massachusetts died. EEEV is transmitted in
      marshes and swamps in an enzootic bird-mosquito-bird cycle primarily by the
      mosquito Culiseta melanura. Bridge mosquito vectors (e.g., Coquillettidia
      perturbans, Aedes vexans, or Aedes sollicitans) transmit EEEV to humans and other
      mammals. This report summarizes the investigations of cases in New Hampshire and
      Massachusetts conducted by the two state health departments and CDC. The findings
      underscore the importance of surveillance for, and diagnostic consideration of,
      arboviral encephalitis in the United States and promotion of preventive measures
      such as local mosquito control and use of insect repellent.

PMID- 16810148
TI  - Human salmonellosis associated with animal-derived pet treats--United States and
      Canada, 2005.
AB  - During 2004-2005, contact with Salmonella-contaminated pet treats of beef and
      seafood origin resulted in nine culture-confirmed human Salmonella Thompson
      infections in western Canada and the state of Washington. This is the third
      published report of an outbreak of human illness associated with pet treats in
      North America and the first to describe such an outbreak in the United States.
      This report highlights the investigation of the outbreak by U.S. and Canadian
      public health officials and provides recommendations for reducing the risk that
      Salmonella-contaminated pet treats pose to humans. Public health practitioners
      should consider pet treats a potential source for Salmonella transmission.

PMID- 16810147
TI  - Travel-associated dengue--United States, 2005.
AB  - Dengue is a mosquito-transmitted, acute viral disease caused by any of four
      dengue virus serotypes (DEN-1, DEN-2, DEN-3, or DEN-4). Dengue is endemic in most
      tropical and subtropical areas of the world and has occurred among U.S. residents
      returning from travel to such areas. In collaboration with state health
      departments, CDC maintains a passive surveillance system for travel-associated
      dengue among U.S. residents. Suspected dengue in travelers is reported to state
      health departments, which forward specimens to CDC for diagnostic testing. A case
      of travel-associated dengue is defined as laboratory-diagnosed dengue in a
      resident of one of the 50 states or the District of Columbia (DC) who traveled to
      a dengue-endemic area outside the United States or DC any time during the 14 days
      before symptom onset. This report summarizes information regarding 96 travel
      associated dengue cases, including one fatality, among U.S. residents during
      2005. Travelers to tropical areas can reduce their risk for dengue by using
      mosquito repellent and avoiding exposure to mosquitoes. Health-care providers
      should consider dengue in the differential diagnosis of febrile illness in
      patients who have returned recently from dengue-endemic areas.

PMID- 16810149
TI  - Ablation for atrial fibrillation.

PMID- 16810150
TI  - The future of left ventricular assist device therapy in adults.

PMID- 16810165
TI  - Can intensive statin therapy cause regression of coronary atherosclerosis?

PMID- 16810166
TI  - Is facilitated percutaneous coronary intervention superior to primary
      percutaneous coronary intervention?

PMID- 16810167
TI  - Can fondaparinux safely prevent the occurrence of venous thromboembolism in
      acutely ill medical patients?

PMID- 16810168
TI  - Should aprotinin continue to be used during cardiac surgery?

PMID- 16810169
TI  - Can brain natriuretic peptide levels aid diagnosis in children with congenital
      heart disease?

PMID- 16810170
TI  - Is rimonabant a safe and effective therapy for sustained weight loss and improved
      cardiometabolic risk factors?

PMID- 16810171
TI  - Can ACAT inhibition limit the progression of atherosclerosis in patients with
      coronary artery disease?

PMID- 16810172
TI  - Diastolic ventricular interaction: from physiology to clinical practice.
AB  - The ventricles share a common septum and, therefore, the filling of one
      influences the compliance of the other. This phenomenon is known as direct
      diastolic ventricular interaction. The interaction is noticeably increased when
      the force exerted by the surrounding pericardium is raised, which is termed
      pericardial constraint. In healthy individuals, pericardial constraint is minor
      in the resting state. When right ventricular volume-to-pressure ratio acutely
      increases, however, such as during exercise, massive pulmonary embolism, or right
      ventricular infarction, notable diastolic ventricular interaction occurs. In this
      setting, the measured left ventricular intracavitary diastolic pressure
      overestimates the true left ventricular filling pressure, because the effect of
      external forces must be subtracted. Although growth of the pericardium can be a
      feature of chronic cardiac enlargement, here we review the evidence of the
      importance of diastolic ventricular interaction in certain acute and chronic
      disease processes, including heart failure.

PMID- 16810173
TI  - Technology insight: Use of ventricular assist devices in children.
AB  - Mechanical circulatory support systems for the treatment of end-stage heart
      failure are now available for a wide variety of clinical situations and support
      times. Extracorporeal membrane oxygenation and centrifugal pump circuits have
      been most widely used in children, particularly in small infants. These systems
      are preferred for support after cardiac operations and for use in patients who
      have concomitant respiratory failure, but are suitable for short-term application
      only and intensive care is obligatory. True ventricular assist devices (VADs)
      qualify for long-term application and allow patients full mobilization. These
      features are important in patients awaiting heart transplantation as well as in
      those with myocarditis and cardiomyopathy, who might achieve complete cardiac
      recovery. Pneumatic pulsatile VADs have been available in pediatric sizes since
      1992. At our institution, VAD use lasting from several days to 14 months in 70
      infants and children with myocarditis and cardiomyopathy has led to a notable
      rise in survival in the past 5 years. We have been able to discharge 78% of the
      infants under 1 year old. In this review we present current VAD experience in
      children in the light of improvements in decision making, device technology,
      implantation techniques, and in coagulation monitoring and anticoagulation.

PMID- 16810174
TI  - Drug insight: Clopidogrel nonresponsiveness.
AB  - Platelet reactivity to agonists and subsequent activation are important factors
      that affect the development of atherothrombosis and resultant ischemic events.
      Pharmacologic intervention with clopidogrel and aspirin during acute coronary
      syndromes and percutaneous coronary intervention is considered the gold standard
      for attenuating platelet activation and aggregation. Despite significant benefits
      reported with dual antiplatelet treatment in major clinical trials, the
      occurrence of adverse ischemic events, including stent thrombosis, remains a
      serious clinical problem. Nonresponsiveness, also called resistance, to current
      clopidogrel regimens might play a part in the occurrence of ischemic events.
      Various mechanisms have been implicated in nonresponsiveness to clopidogrel,
      including variability in intestinal absorption and hepatic conversion to the
      active metabolite, drug-drug interactions and receptor polymorphisms. Increased
      loading and maintenance doses and the use of new and more-potent P2Y12-receptor
      blockers might overcome the phenomenon of clopidogrel nonresponsiveness. The aim
      of this article is to provide a comprehensive and current review of clopidogrel
      response variability and nonresponsiveness.

PMID- 16810175
TI  - Aortic thrombus and pulmonary embolism in a patient with hyperhomocysteinemia.
AB  - BACKGROUND: A 32-year-old man presented at hospital with persistent pain,
      hypothermia and paraesthesia in his right leg, caused by embolic occlusion of all
      three large arteries as a result of massive thrombi in the abdominal aorta.
      Previously, the patient had been diagnosed with pulmonary embolism and admitted
      at least a 6-month history of alcohol abuse. Laboratory assessment of the
      patient's lipid levels, platelet function and coagulation factors yielded normal
      results. Duplex ultrasound revealed substantial media thickening of the carotid
      and femoral arteries, without evidence of calcification. Further laboratory tests
      revealed elevated plasma levels of homocysteine, asymmetric dimethylarginine,
      symmetric dimethylarginine and 8-isoprostaglandin F2alpha. INVESTIGATIONS:
      Physical examination, laboratory analyses, bronchoscopy, duplex ultrasonography,
      CT scan and CT angiography. DIAGNOSIS: Severe hyperhomocysteinemia associated
      with acute aortic thrombi and peripheral emboli. MANAGEMENT: Diet supplementation
      with folic acid, vitamin B6 and vitamin B12, low-molecular-weight heparin and L
      arginine.

PMID- 16810176
TI  - Hierarchy and adaptivity in segmenting visual scenes.
AB  - Finding salient, coherent regions in images is the basis for many visual tasks,
      and is especially important for object recognition. Human observers perform this
      task with ease, relying on a system in which hierarchical processing seems to
      have a critical role. Despite many attempts, computerized algorithms have so far
      not demonstrated robust segmentation capabilities under general viewing
      conditions. Here we describe a new, highly efficient approach that determines all
      salient regions of an image and builds them into a hierarchical structure. Our
      algorithm, segmentation by weighted aggregation, is derived from algebraic
      multigrid solvers for physical systems, and consists of fine-to-coarse pixel
      aggregation. Aggregates of various sizes, which may or may not overlap, are
      revealed as salient, without predetermining their number or scale. Results using
      this algorithm are markedly more accurate and significantly faster (linear in
      data size) than previous approaches.

PMID- 16810177
TI  - The physical basis of how prion conformations determine strain phenotypes.
AB  - A principle that has emerged from studies of protein aggregation is that proteins
      typically can misfold into a range of different aggregated forms. Moreover, the
      phenotypic and pathological consequences of protein aggregation depend critically
      on the specific misfolded form. A striking example of this is the prion strain
      phenomenon, in which prion particles composed of the same protein cause distinct
      heritable states. Accumulating evidence from yeast prions such as [PSI+] and
      mammalian prions argues that differences in the prion conformation underlie prion
      strain variants. Nonetheless, it remains poorly understood why changes in the
      conformation of misfolded proteins alter their physiological effects. Here we
      present and experimentally validate an analytical model describing how [PSI+]
      strain phenotypes arise from the dynamic interaction among the effects of prion
      dilution, competition for a limited pool of soluble protein, and conformation
      dependent differences in prion growth and division rates. Analysis of three
      distinct prion conformations of yeast Sup35 (the [PSI+] protein determinant) and
      their in vivo phenotypes reveals that the Sup35 amyloid causing the strongest
      phenotype surprisingly shows the slowest growth. This slow growth, however, is
      more than compensated for by an increased brittleness that promotes prion
      division. The propensity of aggregates to undergo breakage, thereby generating
      new seeds, probably represents a key determinant of their physiological impact
      for both infectious (prion) and non-infectious amyloids.

PMID- 16810178
TI  - Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and
      axonal growth.
AB  - In the developing nervous system, Id2 (inhibitor of DNA binding 2, also known as
      inhibitor of differentiation 2) enhances cell proliferation, promotes tumour
      progression and inhibits the activity of neurogenic basic helix-loop-helix (bHLH)
      transcription factors. The anaphase promoting complex/cyclosome and its activator
      Cdh1 (APC/C(Cdh1)) restrains axonal growth but the targets of APC/C(Cdh1) in
      neurons are unknown. Id2 and other members of the Id family are very unstable
      proteins that are eliminated as cells enter the quiescent state, but how they are
      targeted for degradation has remained elusive. Here we show that Id2 interacts
      with the core subunits of APC/C and Cdh1 in primary neurons. APC/C(Cdh1) targets
      Id2 for degradation through a destruction box motif (D box) that is conserved in
      Id1 and Id4. Depletion of Cdh1 stabilizes Id proteins in neurons, whereas Id2 D
      box mutants are impaired for Cdh1 binding and remain stable in cells that exit
      from the cell cycle and contain active APC/C(Cdh1). Mutants of the Id2 D box
      enhance axonal growth in cerebellar granule neurons in vitro and in the context
      of the cerebellar cortex, and overcome the myelin inhibitory signals for growth.
      Conversely, activation of bHLH transcription factors induces a cluster of genes
      with potent axonal inhibitory functions including the gene coding for the Nogo
      receptor, a key transducer of myelin inhibition. Degradation of Id2 in neurons
      permits the accumulation of the Nogo receptor, thereby linking APC/C(Cdh1)
      activity with bHLH target genes for the inhibition of axonal growth. These
      findings indicate that deregulated Id activity might be useful to reprogramme
      quiescent neurons into the axonal growth mode.

PMID- 16810179
TI  - Sildenafil citrate (Viagra) treatment for erectile dysfunction: An updated
      profile of response and effectiveness.
AB  - In the 7 years since sildenafil citrate (VIAGRA) was introduced as the first oral
      phosphodiesterase type 5 inhibitor therapy for erectile dysfunction, it has been
      used to treat nearly 27 million men with erectile dysfunction worldwide. Patient
      populations with erectile dysfunction of varying etiologies and with diverse
      comorbidities have benefited from sildenafil treatment. This update focuses on
      relatively recent research that further defines the response and effectiveness
      profiles of sildenafil and provides additional insight into optimizing treatment.
      In addition to providing recent data on sildenafil efficacy and
      safety/tolerability, the update provides data on assessments of erection
      hardness, measures of psychosocial outcomes (e.g., emotional well-being and
      treatment satisfaction), and treatment approaches to maximize response and
      effectiveness (e.g., by titrating to the maximum tolerated dose). Increased
      understanding of the sildenafil response and effectiveness profiles and optimal
      sildenafil treatment are central to the appropriate management of erectile
      dysfunction using sildenafil.

PMID- 16810195
TI  - Experimental study of bone marrow-derived mesenchymal stem cells combined with
      hepatocyte growth factor transplantation via noninfarct-relative artery in acute
      myocardial infarction.
AB  - We investigated the impact of bone marrow-derived mesenchymal stem cells (BM
      MSCs) alone or in combination with hepatocyte growth factor (HGF) transplantation
      via noninfarct-relative artery in a swine myocardial infarction (MI) model. Donor
      BM-MSCs were derived in vitro from swine auto-bone marrow cultures labeled by
      bromodeoxyuridine (BrdU) incorporation. Host MI swine model was created by
      ligating the distal left anterior descending artery. After 4 weeks, age-matched
      male MI swines were used for the transplantation. Male MI swines were transfused
      via noninfarct-relative artery with vehicle (control, n=6) or BrdU-labeled BM
      MSCs (5 x 10(6)) alone (MSCs, n=6) or BrdU-labeled BM-MSCs (5 x 10(6)) combined
      with HGF (4 x 10(9) PFU) (MSCs+HGF, n=6). To evaluate the collateral artery
      growth (Rentrop) and cardiac perfusion in these animals, gate cardiac perfusion
      imaging and coronary angiography were performed before and 4 weeks after
      transplantation, respectively. To assess the contribution of donor-originated
      cells in stimulation of cardiomyocyte regeneration and angiogenesis,
      immunohistochemistry for BrdU and alpha-smooth muscle actin (alpha-SMA) and
      quantitative image analysis were performed at 4 weeks after transplantation. The
      results are as follows: (1) BrdU-positive cells were detected in host myocardium
      in both MSCs and MSCs+HGF groups, but not in the vehicle group. Most BrdU
      positive cells expressed myosin heavy chain beta. (2) alpha-SMA(-)positive
      arteriole densities in the infarcted border area and infarcted area were
      increased significantly in both transplantation groups compared with the vehicle
      group. (3) Gate cardiac perfusion imaging demonstrated that the cardiac perfusion
      was significantly improved in transplantation groups compared with the vehicle
      group. (4) Ejection fraction and alpha-SMA-positive arteriole densities were
      increased significantly in both transplantation groups compared with the vehicle
      group. However, there was no difference in ejection fraction and alpha-SMA
      positive arteriole densities between the MSCs group and the MSCs+HGF group.
      Growth of collateral arteries was not detected by coronary angiography in all
      three groups. In conclusion, the current study indicates that BM-MSCs
      transplantation via noninfarct-relative artery stimulates cardiomyocyte
      regeneration and angiogenesis and improves cardiac function, but does not
      stimulate collateral artery growth. BM-MSCs transplantation combined with HGF
      therapy is not superior to BM-MSCs alone transplantation. BM-MSCs transplantation
      via noninfarct-relative artery may be an alternative for those patients who
      cannot be transplanted via infarct-relative artery in clinical practice.

PMID- 16810196
TI  - Use of synthetic vectors for neutralising antibody resistant delivery of
      replicating adenovirus DNA.
AB  - Use of synthetic vectors to deliver genomes of conditionally replicating lytic
      viruses combines the strengths of viral and non-viral approaches by enabling
      neutralising antibody resistant deployment of cancer virotherapy. Adenovirus is
      particularly suitable for this application since all proteins essential for
      replication can be expressed from the input DNA, although the presence of
      terminal protein (TP) covalently linked to the 5' termini of the input virus
      genomes both improves expression of transgenes encoded in the input DNA and also
      enhances replication. These roles of TP were distinguished in experiments where
      E1-deleted Ad(GFP)DNA bearing TP (Ad(GFP)DNA-TP), delivered with DOTAP, gave a
      two-fold greater frequency of transduction than Ad(GFP)DNA(without TP) in non
      complementing A549 cells, while in 293 cells (which support replication of E1
      deleted viruses) the presence of TP mediated a much greater differential
      transgene expression, commensurate with its ability to promote replication.
      Subsequent studies using AdDNA for virotherapy, therefore, included covalently
      linked TP. AdDNA-TP delivered to A549 cells using a synthetic polyplex vector was
      shown to be resistant to levels of neutralising antisera that completely ablated
      infection by wild-type adenovirus, enabling polyplex/Ad(wild type)DNA-TP to
      mediate a powerful cytopathic effect. Similarly in vivo, direct injection of a
      polyplex/Ad(wild type)DNA-TP into A549 tumours was neutralising antibody
      resistant and enabled virus replication, whereas intact virus was neutralised by
      the antibody and failed to infect. The delivery of adenovirus genomes-TP using
      synthetic vectors should provide a strategy to bypass neutralising antibodies and
      facilitate clinical application of replicating adenovirus for cancer virotherapy.

PMID- 16810197
TI  - A guanylate kinase/HSV-1 thymidine kinase fusion protein enhances prodrug
      mediated cell killing.
AB  - Herpes simplex virus thymidine kinase (HSVTK) with the guanosine analog
      ganciclovir (GCV) is currently the most widely used suicide gene/prodrug system
      for gene therapy of cancer. Despite the broad application of the HSVTK/GCV
      approach, phosphorylation of GCV to its active state is inefficient such that
      high, myelosuppressive doses of GCV are needed to observe an antitumor effect.
      One strategy used to overcome the poor substrate specificity of HSVTK towards GCV
      (Km = 45 microM) has been to create novel forms of TK with altered substrate
      preferences. Such mutant TKs have shown benefit and are currently in clinical
      use. We describe here a second strategy to increase the amount of intracellular
      triphosphorylated GCV by involving the second enzyme in the GCV activation
      pathway, guanylate kinase (GMK). As a means to overcome the bottleneck of prodrug
      activation from the monophosphate to the diphosphate, we sought to combine both
      the critical HSVTK and GMK activities together. In this report we describe the
      construction of a fusion or chimeric protein of HSVTK and guanylate kinase, show
      data that demonstrate it confers a approximately 175-fold decrease in IC50
      compared to HSVTK alone in response to ganciclovir treatment in stably
      transfected C6 glioma cells and finally, we present biochemical evidence of a
      kinetic basis for this improved cell killing.

PMID- 16810198
TI  - Non-classical antileukemia activity of early recovering NK cells after induction
      chemotherapy and HLA-identical stem cell transplantation in myeloid leukemias.

PMID- 16810199
TI  - MN1-TEL, the product of the t(12;22) in human myeloid leukemia, immortalizes
      murine myeloid cells and causes myeloid malignancy in mice.
AB  - MN1-TEL is the product of the recurrent t(12;22)(p12;q11) associated with human
      myeloid malignancies. MN1-TEL functions as an activated transcription factor,
      exhibiting weak transforming activity in NIH3T3 fibroblasts that depends on the
      presence of a functional TEL DNA-binding domain, the N-terminal transactivating
      sequences of MN1 and C-terminal sequences of MN1. We determined the transforming
      activity of MN1-TEL in mouse bone marrow (BM) by using retroviral transfer. MN1
      TEL-transduced BM showed increased self-renewal capacity of primitive progenitors
      in vitro, and prolonged in vitro culture of MN1-TEL-expressing BM produced
      immortalized myeloid, interleukin (IL)-3/stem cell factor-dependent cell lines
      with a primitive morphology. Transplantation of such cell lines into lethally
      irradiated mice rescued them from irradiation-induced death and resulted in the
      contribution of MN1-TEL-expressing cells to all hematopoietic lineages,
      underscoring the primitive nature of these cells and their capacity to
      differentiate in vivo. Three months after transplantation, all mice succumbed to
      promonocytic leukemia. Transplantation of freshly MN1-TEL-transduced BM into
      lethally irradiated mice also caused acute myeloid leukemia within 3 months of
      transplantation. We infer that MN1-TEL is a hematopoietic oncogene that
      stimulates the growth of hematopoietic cells, but depends on secondary mutations
      to cause leukemia in mice.

PMID- 16810200
TI  - Myeloproliferative disorders: premalignant, stem cell, G1 diseases?

PMID- 16810201
TI  - Association of the heterozygous germline I171V mutation of the NBS1 gene with
      childhood acute lymphoblastic leukemia.

PMID- 16810202
TI  - Histone deacetylase inhibitors have antitumor activity in two NOD/SCID mouse
      models of B-cell precursor childhood acute lymphoblastic leukemia.

PMID- 16810207
TI  - Science in the Arab world.

PMID- 16810203
TI  - Proteasome inhibitor bortezomib for the treatment of multiple myeloma.
AB  - Bortezomib (formerly PS-341) has been the first proteasome inhibitor to enter
      clinical trials in cancer patients. Based on results of preclinical studies
      showing that this novel agent directly inhibits the proliferation of myeloma
      cells, induces their apoptosis and abrogates paracrine tumor growth through
      alteration of myeloma-stromal cell interactions and nuclear factor-kappaB
      dependent cytokine secretion, several large phase II and III studies of
      bortezomib were initiated in patients with advanced relapsed and/or refractory
      multiple myeloma (MM). Favorable results of these studies led to accelerated
      approval for use of bortezomib in MM patients who have progressed after at least
      their second therapy and, more recently, to expanded approval for second-line use
      in patients on whom one prior therapy has failed. In the meantime, combination
      studies of bortezomib with various agents, including dexamethasone, DNA-damaging
      drugs, thalidomide and lenalidomide, have been designed and are currently ongoing
      in patients with both relapsed/refractory and newly diagnosed disease. Bortezomib
      offers great promise to overcome resistance to conventional chemotherapy and may
      be the 'backbone' for the development of more effective treatment strategies to
      improve patient outcome in MM.

PMID- 16810208
TI  - Action stations.

PMID- 16810211
TI  - Academy affirms hockey-stick graph.

PMID- 16810212
TI  - Experts comb tropics for clues to vCJD.

PMID- 16810213
TI  - Hunt for AIDS vaccine tackles genomes.

PMID- 16810214
TI  - Hungary's science academy slammed as 'obsolete'.

PMID- 16810216
TI  - Scientists become targets in Iraq.

PMID- 16810217
TI  - Human eggs supply 'ethical' stem cells.

PMID- 16810221
TI  - Assault on batteries.

PMID- 16810220
TI  - Science on the solstice.

PMID- 16810225
TI  - Public will fear biological accidents, not just attacks.

PMID- 16810226
TI  - Researchers frustrated by lack of input to NIH policy.

PMID- 16810227
TI  - Discrete reminder about Weismann's discovery.

PMID- 16810228
TI  - Seeing is believing as brain reveals its adaptability.

PMID- 16810233
TI  - Quantum physics: atomic gas in flatland.

PMID- 16810235
TI  - Materials science: germanium takes holey orders.

PMID- 16810234
TI  - Structural biology: RNA switches function.

PMID- 16810236
TI  - Astronomy: supernovae brought to light.

PMID- 16810237
TI  - Neurodegenerative disease: pink, parkin and the brain.

PMID- 16810240
TI  - Nuclear reprogramming and pluripotency.
AB  - The cloning of mammals from differentiated donor cells has refuted the old dogma
      that development is an irreversible process. It has demonstrated that the oocyte
      can reprogramme an adult nucleus into an embryonic state that can direct
      development of a new organism. The prospect of deriving patient-specific
      embryonic stem cells by nuclear transfer underscores the potential use of this
      technology in regenerative medicine. The future challenge will be to study
      alternatives to nuclear transfer in order to recapitulate reprogramming in a
      Petri dish without the use of oocytes.

PMID- 16810241
TI  - Asymmetric and symmetric stem-cell divisions in development and cancer.
AB  - Much has been made of the idea that asymmetric cell division is a defining
      characteristic of stem cells that enables them to simultaneously perpetuate
      themselves (self-renew) and generate differentiated progeny. Yet many stem cells
      can divide symmetrically, particularly when they are expanding in number during
      development or after injury. Thus, asymmetric division is not necessary for stem
      cell identity but rather is a tool that stem cells can use to maintain
      appropriate numbers of progeny. The facultative use of symmetric or asymmetric
      divisions by stem cells may be a key adaptation that is crucial for adult
      regenerative capacity.

PMID- 16810242
TI  - The stem-cell niche as an entity of action.
AB  - Stem-cell populations are established in 'niches'--specific anatomic locations
      that regulate how they participate in tissue generation, maintenance and repair.
      The niche saves stem cells from depletion, while protecting the host from over
      exuberant stem-cell proliferation. It constitutes a basic unit of tissue
      physiology, integrating signals that mediate the balanced response of stem cells
      to the needs of organisms. Yet the niche may also induce pathologies by imposing
      aberrant function on stem cells or other targets. The interplay between stem
      cells and their niche creates the dynamic system necessary for sustaining
      tissues, and for the ultimate design of stem-cell therapeutics.

PMID- 16810243
TI  - Stem cells, ageing and the quest for immortality.
AB  - Adult stem cells reside in most mammalian tissues, but the extent to which they
      contribute to normal homeostasis and repair varies widely. There is an overall
      decline in tissue regenerative potential with age, and the question arises as to
      whether this is due to the intrinsic ageing of stem cells or, rather, to the
      impairment of stem-cell function in the aged tissue environment. Unravelling
      these distinct contributions to the aged phenotype will be critical to the
      success of any therapeutic application of stem cells in the emerging field of
      regenerative medicine with respect to tissue injury, degenerative diseases or
      normal functional declines that accompany ageing.

PMID- 16810244
TI  - Generation of neuronal variability and complexity.
AB  - The production of specialized differentiated neurons derived from stem cells has
      been proposed as a revolutionary technology for regenerative medicine. However,
      few examples of specific neuronal cell differentiation have been described so
      far. Although stem-cell tissue replacement might be seemingly straightforward in
      other cases, the high degree of complexity of the nervous system raises the
      challenge of tissue replacement substantially. Understanding mechanisms of
      neuronal diversification will not only be relevant for therapeutic purposes but
      might also shed light on the differences in cognitive abilities, personality
      traits and psychiatric conditions observed in humans.

PMID- 16810245
TI  - Stem cells for the treatment of neurological disorders.
AB  - Many common neurological disorders, such as Parkinson's disease, stroke and
      multiple sclerosis, are caused by a loss of neurons and glial cells. In recent
      years, neurons and glia have been generated successfully from stem cells in
      culture, fueling efforts to develop stem-cell-based transplantation therapies for
      human patients. More recently, efforts have been extended to stimulating the
      formation and preventing the death of neurons and glial cells produced by
      endogenous stem cells within the adult central nervous system. The next step is
      to translate these exciting advances from the laboratory into clinically useful
      therapies.

PMID- 16810246
TI  - Potential of stem-cell-based therapies for heart disease.
AB  - The use of stem cells to generate replacement cells for damaged heart muscle,
      valves, vessels and conduction cells holds great potential. Recent identification
      of multipotent progenitor cells in the heart and improved understanding of
      developmental processes relevant to pluripotent embryonic stem cells may
      facilitate the generation of specific types of cell that can be used to treat
      human heart disease. Secreted factors from circulating progenitor cells that
      localize to sites of damage may also be useful for tissue protection or
      neovascularization. The exciting discoveries in basic science will require
      rigorous testing in animal models to determine those most worthy of future
      clinical trials.

PMID- 16810248
TI  - Soft equations of state for neutron-star matter ruled out by EXO 0748 - 676.
AB  - The interiors of neutron stars contain matter at very high densities, in a state
      that differs greatly from those found in the early Universe or achieved in
      terrestrial experiments. Matter in these conditions can only be probed through
      astrophysical observations that measure the mass and radius of neutron stars with
      sufficient precision. Here I report a determination of the mass and radius of the
      neutron star EXO 0748 - 676 that appears to rule out all the soft equations of
      state of neutron-star matter. If this object is typical, then condensates and
      unconfined quarks do not exist in the centres of neutron stars.

PMID- 16810247
TI  - Stem-cell therapies for blood diseases.
AB  - For decades, transplantation of haematopoietic stem cells--either unmodified, or
      genetically modified to correct genetic disorders--has been used to treat
      disorders of the blood and immune systems. The present challenge is to reduce the
      risk of such transplants and increase the number of patients who can safely
      access this treatment. In developing countries, such 'one-shot' treatments are
      highly desirable because chronic treatments are difficult to sustain. To make
      these therapies more accessible and effective it will be important to improve
      clinical protocols and gene-delivery vectors, and to gain a deeper understanding
      of stem cells.

PMID- 16810249
TI  - Berezinskii-Kosterlitz-Thouless crossover in a trapped atomic gas.
AB  - Any state of matter is classified according to its order, and the type of order
      that a physical system can possess is profoundly affected by its dimensionality.
      Conventional long-range order, as in a ferromagnet or a crystal, is common in
      three-dimensional systems at low temperature. However, in two-dimensional systems
      with a continuous symmetry, true long-range order is destroyed by thermal
      fluctuations at any finite temperature. Consequently, for the case of identical
      bosons, a uniform two-dimensional fluid cannot undergo Bose-Einstein
      condensation, in contrast to the three-dimensional case. However, the two
      dimensional system can form a 'quasi-condensate' and become superfluid below a
      finite critical temperature. The Berezinskii-Kosterlitz-Thouless (BKT) theory
      associates this phase transition with the emergence of a topological order,
      resulting from the pairing of vortices with opposite circulation. Above the
      critical temperature, proliferation of unbound vortices is expected. Here we
      report the observation of a BKT-type crossover in a trapped quantum degenerate
      gas of rubidium atoms. Using a matter wave heterodyning technique, we observe
      both the long-wavelength fluctuations of the quasi-condensate phase and the free
      vortices. At low temperatures, the gas is quasi-coherent on the length scale set
      by the system size. As the temperature is increased, the loss of long-range
      coherence coincides with the onset of proliferation of free vortices. Our results
      provide direct experimental evidence for the microscopic mechanism underlying the
      BKT theory, and raise new questions regarding coherence and superfluidity in
      mesoscopic systems.

PMID- 16810250
TI  - Mesostructured germanium with cubic pore symmetry.
AB  - Regular mesoporous oxide materials have been widely studied and have a range of
      potential applications, such as catalysis, absorption and separation. They are
      not generally considered for their optical and electronic properties. Elemental
      semiconductors with nanopores running through them represent a different form of
      framework material with physical characteristics contrasting with those of the
      more conventional bulk, thin film and nanocrystalline forms. Here we describe
      cubic mesostructured germanium, MSU-Ge-1, with gyroidal channels containing
      surfactant molecules, separated by amorphous walls that lie on the gyroid (G)
      minimal surface as in the mesoporous silica MCM-48 (ref. 2). Although Ge is a
      high-melting, covalent semiconductor that is difficult to prepare from solution
      polymerization, we succeeded in assembling a continuous Ge network using a
      suitable precursor for Ge(4-) atoms. Our results indicate that elemental
      semiconductors from group 14 of the periodic table can be made to adopt
      mesostructured forms such as MSU-Ge-1, which features two three-dimensional
      labyrinthine tunnels obeying Ia3d space group symmetry and separated by a
      continuous germanium minimal surface that is otherwise amorphous. A consequence
      of this new structure for germanium, which has walls only one nanometre thick, is
      a wider electronic energy bandgap (1.4 eV versus 0.66 eV) than has crystalline or
      amorphous Ge. Controlled oxidation of MSU-Ge-1 creates a range of germanium
      suboxides with continuously varying Ge:O ratio and a smoothly increasing energy
      gap.

PMID- 16810251
TI  - Hexagonal nanoporous germanium through surfactant-driven self-assembly of Zintl
      clusters.
AB  - Surfactant templating is a method that has successfully been used to produce
      nanoporous inorganic structures from a wide range of oxide-based material. Co
      assembly of inorganic precursor molecules with amphiphilic organic molecules is
      followed first by inorganic condensation to produce rigid amorphous frameworks
      and then, by template removal, to produce mesoporous solids. A range of periodic
      surfactant/semiconductor and surfactant/metal composites have also been produced
      by similar methods, but for virtually all the non-oxide semiconducting phases,
      the surfactant unfortunately cannot be removed to generate porous materials. Here
      we show that it is possible to use surfactant-driven self-organization of soluble
      Zintl clusters to produce periodic, nanoporous versions of classic semiconductors
      such as amorphous Ge or Ge/Si alloys. Specifically, we use derivatives of the
      anionic Ge9(4-) cluster, a compound whose use in the synthesis of nanoscale
      materials is established. Moreover, because of the small size, high surface area,
      and flexible chemistry of these materials, we can tune optical properties in
      these nanoporous semiconductors through quantum confinement, by adsorption of
      surface species, or by altering the elemental composition of the inorganic
      framework. Because the semiconductor surface is exposed and accessible in these
      materials, they have the potential to interact with a range of species in ways
      that could eventually lead to new types of sensors or other novel nanostructured
      devices.

PMID- 16810252
TI  - Subcontinental-scale crustal velocity changes along the Pacific-North America
      plate boundary.
AB  - Transient tectonic deformation has long been noted within approximately 100 km of
      plate boundary fault zones and within active volcanic regions, but it is unknown
      whether transient motions also occur at larger scales within plates. Relatively
      localized transients are known to occur as both seismic and episodic aseismic
      events, and are generally ascribed to motions of magma bodies, aseismic creep on
      faults, or elastic or viscoelastic effects associated with earthquakes. However,
      triggering phenomena and systematic patterns of seismic strain release at
      subcontinental (approximately 1,000 km) scale along diffuse plate boundaries have
      long suggested that energy transfer occurs at larger scale. Such transfer appears
      to occur by the interaction of stresses induced by surface wave propagation and
      magma or groundwater in the crust, or from large-scale stress diffusion within
      the oceanic mantle in the decades following clusters of great earthquakes. Here
      we report geodetic evidence for a coherent, subcontinental-scale change in
      tectonic velocity along a diffuse approximately 1,000-km-wide deformation zone.
      Our observations are derived from continuous GPS (Global Positioning System) data
      collected over the past decade across the Basin and Range province, which absorbs
      approximately 25 per cent of Pacific-North America relative plate motion. The
      observed changes in site velocity define a sharp boundary near the centre of the
      province oriented roughly parallel to the north-northwest relative plate motion
      vector. We show that sites to the west of this boundary slowed relative to sites
      east of it by approximately 1 mm yr(-1) starting in late 1999.

PMID- 16810253
TI  - Seismic waves increase permeability.
AB  - Earthquakes have been observed to affect hydrological systems in a variety of
      ways--water well levels can change dramatically, streams can become fuller and
      spring discharges can increase at the time of earthquakes. Distant earthquakes
      may even increase the permeability in faults. Most of these hydrological
      observations can be explained by some form of permeability increase. Here we use
      the response of water well levels to solid Earth tides to measure permeability
      over a 20-year period. At the time of each of seven earthquakes in Southern
      California, we observe transient changes of up to 24 degrees in the phase of the
      water level response to the dilatational volumetric strain of the semidiurnal
      tidal components of wells at the Pinon Flat Observatory in Southern California.
      After the earthquakes, the phase gradually returns to the background value at a
      rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven
      by an imposed head oscillation through a single, laterally extensive, confined,
      homogeneous and isotropic aquifer to relate the phase response to aquifer
      properties. We interpret the changes in phase response as due to changes in
      permeability. At the time of the earthquakes, the permeability at the site
      increases by a factor as high as three. The permeability increase depends roughly
      linearly on the amplitude of seismic-wave peak ground velocity in the range of
      0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists
      and oil reservoir engineers as they affect fluid flow and might determine long
      term evolution of hydrological and oil-bearing systems. They may also be
      interesting to seismologists, as the resulting pore pressure changes can affect
      earthquakes by changing normal stresses on faults.

PMID- 16810254
TI  - Diversity and dispersal interactively affect predictability of ecosystem
      function.
AB  - Theory and small-scale experiments predict that biodiversity losses can decrease
      the magnitude and stability of ecosystem services such as production and nutrient
      cycling. Most of this research, however, has been isolated from the immigration
      and emigration (dispersal) processes that create and maintain diversity in
      nature. As common anthropogenic drivers of biodiversity change--such as habitat
      fragmentation, species introductions and climate change--are mediated by these
      understudied processes, it is unclear how environmental degradation will affect
      ecosystem services. Here we tested the interactive effects of mobile grazer
      diversity and dispersal on the magnitude and stability of ecosystem properties in
      experimental seagrass communities that were either isolated or connected by
      dispersal corridors. We show that, contrary to theoretical predictions,
      increasing the number of mobile grazer species in these metacommunities increased
      the spatial and temporal variability of primary and secondary production.
      Moreover, allowing grazers to move among and select patches reduced diversity
      effects on production. Finally, effects of diversity on stability differed
      qualitatively between patch and metacommunity scales. Our results indicate that
      declining biodiversity and habitat fragmentation synergistically influence the
      predictability of ecosystem functioning.

PMID- 16810255
TI  - Activity-dependent dynamics and sequestration of proteasomes in dendritic spines.
AB  - The regulated degradation of proteins by the ubiquitin proteasome pathway is
      emerging as an important modulator of synaptic function and plasticity. The
      proteasome is a large, multi-subunit cellular machine that recognizes, unfolds
      and degrades target polyubiquitinated proteins. Here we report NMDA (N-methyl-D
      aspartate) receptor-dependent redistribution of proteasomes from dendritic shafts
      to synaptic spines upon synaptic stimulation, providing a mechanism for local
      protein degradation. Using a proteasome-activity reporter and local perfusion, we
      show that synaptic stimulation regulates proteasome activity locally in the
      dendrites. We used restricted photobleaching of individual spines and dendritic
      shafts to reveal the dynamics that underlie proteasome sequestration, and show
      that activity modestly enhances the entry rate of proteasomes into spines while
      dramatically reducing their exit rate. Proteasome sequestration is persistent,
      reflecting an association with the actin-based cytoskeleton. Together, our data
      indicate that synaptic activity can promote the recruitment and sequestration of
      proteasomes to locally remodel the protein composition of synapses.

PMID- 16810256
TI  - Nodulation independent of rhizobia induced by a calcium-activated kinase lacking
      autoinhibition.
AB  - Legumes, such as Medicago truncatula, form mutualistic symbiotic relationships
      with nitrogen-fixing rhizobial bacteria. This occurs within specialized root
      organs--nodules--that provide the conditions required for nitrogen fixation. A
      rhizobium-derived signalling molecule, Nod factor, is required to establish the
      symbiosis. Perception of Nod factor in the plant leads to the induction of Ca2+
      oscillations, and the transduction of this Ca2+ signal requires DMI3 (refs 2, 3),
      which encodes the protein kinase Ca2+/calmodulin-dependent protein kinase
      (CCaMK). Central to the regulation of CCaMK is an autoinhibitory domain that
      negatively regulates kinase activity. Here we show that the specific removal of
      the autoinhibition domain leads to the autoactivation of the nodulation
      signalling pathway in the plant, with the resultant induction of nodules and
      nodulation gene expression in the absence of bacterial elicitation. This
      autoactivation requires nodulation-specific transcriptional regulators in the
      GRAS family. This work demonstrates that the release of autoinhibition from CCaMK
      after calmodulin binding is a central switch that is sufficient to activate
      nodule morphogenesis. The fact that a single regulation event is sufficient to
      induce nodulation highlights the possibility of transferring this process to non
      legumes.

PMID- 16810257
TI  - Deregulation of a Ca2+/calmodulin-dependent kinase leads to spontaneous nodule
      development.
AB  - Induced development of a new plant organ in response to rhizobia is the most
      prominent manifestation of legume root-nodule symbiosis with nitrogen-fixing
      bacteria. Here we show that the complex root-nodule organogenic programme can be
      genetically deregulated to trigger de novo nodule formation in the absence of
      rhizobia or exogenous rhizobial signals. In an ethylmethane sulphonate-induced
      snf1 (spontaneous nodule formation) mutant of Lotus japonicus, a single amino
      acid replacement in a Ca2+/calmodulin-dependent protein kinase (CCaMK) is
      sufficient to turn fully differentiated root cortical cells into meristematic
      founder cells of root nodule primordia. These spontaneous nodules are genuine
      nodules with an ontogeny similar to that of rhizobial-induced root nodules,
      corroborating previous physiological studies. Using two receptor-deficient
      genetic backgrounds we provide evidence for a developmentally integrated
      spontaneous nodulation process that is independent of lipochitin-oligosaccharide
      signal perception and oscillations in Ca2+ second messenger levels. Our results
      reveal a key regulatory position of CCaMK upstream of all components required for
      cell-cycle activation, and a phenotypically divergent series of mutant alleles
      demonstrates positive and negative regulation of the process.

PMID- 16810259
TI  - Induction of DNA methylation and gene silencing by short interfering RNAs in
      human cells.

PMID- 16810258
TI  - Structure of the S-adenosylmethionine riboswitch regulatory mRNA element.
AB  - Riboswitches are cis-acting genetic regulatory elements found in the 5'
      untranslated regions of messenger RNAs that control gene expression through their
      ability to bind small molecule metabolites directly. Regulation occurs through
      the interplay of two domains of the RNA: an aptamer domain that responds to
      intracellular metabolite concentrations and an expression platform that uses two
      mutually exclusive secondary structures to direct a decision-making process. In
      Gram-positive bacteria such as Bacillus species, riboswitches control the
      expression of more than 2% of all genes through their ability to respond to a
      diverse set of metabolites including amino acids, nucleobases and protein
      cofactors. Here we report the 2.9-angstroms resolution crystal structure of an S
      adenosylmethionine (SAM)-responsive riboswitch from Thermoanaerobacter
      tengcongensis complexed with S-adenosylmethionine, an RNA element that controls
      the expression of several genes involved in sulphur and methionine metabolism.
      This RNA folds into a complex three-dimensional architecture that recognizes
      almost every functional group of the ligand through a combination of direct and
      indirect readout mechanisms. Ligand binding induces the formation of a series of
      tertiary interactions with one of the helices, serving as a communication link
      between the aptamer and expression platform domains.

PMID- 16810261
TI  - Cell sorting: divide and conquer.

PMID- 16810278
TI  - A large-scale study on relationship between cerebral blood flow velocity and
      blood pressure in a natural population.
AB  - In order to verify the relationship between blood pressure and cerebral blood
      flow velocity in sub-clinical natural population, 1294 middle-aged and old
      Beijing rural residents were investigated in autumn 2002. For all subjects,
      systolic blood flow velocities (V(s)) in common carotid artery (CCA), internal
      carotid artery (ICA) and middle cerebral artery (MCA) were detected with trans
      cranial Doppler. Key factors such as anthropometry, medication use, blood
      pressure and blood biochemical analysis were investigated at the same time. After
      controlling for age, gender, diabetes, hypercholesterolaemia, smoking and body
      mass index, multivariate analysis showed that systolic blood pressure (SBP)
      correlated positively with V(s) at MCA and slight negatively correlated with at
      CCA. As blood pressure rose by 10 mm Hg, the V(s) at MCA increased by 1.63 cm/s.
      Duration of hypertension (HD) negatively correlated with V(s) at MCA (P<0.01).
      The V(s) at MCA in early-stage and chronic hypertensive patients were 92.9+/-1.9
      and 84.1+/-2.3 cm/s, respectively. Antihypertensive treatment could modify the
      V(s) at MCA towards a normal level by lowering blood pressure. In conclusion, the
      effect of hypertension on cerebral blood flow is complex. V(s) at MCA positively
      correlated with SBP, but negatively related to HD. Antihypertensive treatment
      might be helpful to keep cerebral blood flow at a normal level.

PMID- 16810279
TI  - Effects of amlodipine and valsartan on vascular damage and ambulatory blood
      pressure in untreated hypertensive patients.
AB  - The present study was performed to compare the long-term effects of 24-h
      ambulatory blood pressure (BP) control with amlodipine versus valsartan on
      vascular damage in untreated hypertensive patients. Amlodipine and valsartan have
      benefits on cardiovascular mortality and morbidity in hypertensive patients.
      Although ambulatory BP is associated with severity of target-organ damage in
      hypertensive patients, beneficial effects of ambulatory BP control with
      amlodipine versus valsartan on vascular damage have not been compared. Pulse wave
      velocity (PWV), intima-media thickness (IMT) of the carotid arteries, urinary
      albumin excretion (UAE) and 24-h ambulatory BP were determined in 100 untreated
      hypertensive patients before and 12 months after the start of antihypertensive
      therapy with amlodipine or valsartan. Amlodipine and valsartan decreased
      ambulatory BP similarly, but the variability of 24-h and daytime ambulatory
      systolic BP was significantly reduced by amlodipine but not by valsartan. The
      reduced variability of ambulatory systolic BP caused by amlodipine significantly
      contributed to the improvement of PWV, although both drugs decreased PWV
      similarly. Carotid IMT was unaffected by treatment with either drug. Valsartan
      significantly decreased UAE independently of its depressor effect, but amlodipine
      had no effect on UAE. These results suggest that the 24-h control of ambulatory
      BP with amlodipine had functionally improved the stiffened arteries of
      hypertensive patients by the end of 12 months of treatment, in part through
      reducing BP variability, whereas ambulatory BP control with valsartan decreased
      the arterial stiffness to the same degree as amlodipine without affecting BP
      variability maybe through some pleiotropic effects.

PMID- 16810282
TI  - Let us intelligently design a new kidney!

PMID- 16810280
TI  - Severe orthostatic hypotension with diabetic autonomic neuropathy successfully
      treated with a beta(1)-blocker: a case report.

PMID- 16810284
TI  - IgG1 lambda light and heavy chain renal amyloidosis.

PMID- 16810285
TI  - ACE and ACE2: their role to balance the expression of angiotensin II and
      angiotensin-(1-7).
AB  - The discovery of angiotensin-converting enzyme 2 (ACE-2) has revealed a far more
      complex enzymatic cascade that may influence the renin-angiotensin system within
      the kidney, specifically the expression of the functional products angiotensin II
      (Ang II) and Ang-(1-7). The regulation of this critical system involved in blood
      pressure control must now encompass the integral relationship of ACE and ACE-2
      activities.

PMID- 16810286
TI  - Non-invasive assessment of kidney oxygenation: a role for BOLD MRI.
AB  - Blood oxygen level-dependent (BOLD) contrast magnetic resonance imaging (MRI) has
      been applied to investigate kidney oxygenation in human patients. These
      investigations reflect the progress of radiology from a primarily anatomic
      discipline to one that provides insight into tissue physiology. In particular,
      magnetic resonance imaging (MRI) is non-invasive, uses no ionizing radiation, and
      provides insight into disease development and tissue physiology.

PMID- 16810287
TI  - Factor H genotype-phenotype correlations: lessons from aHUS, MPGN II, and AMD.
AB  - Missense mutations in the C-terminal region of Factor H are associated with
      atypical hemolytic uremic syndrome, whereas homozygous Factor H deficiency is
      more frequently associated with membranoproliferative glomerulonephritis type II
      (MPGN II). The report of Licht et al. of a mutation in the complement-regulatory
      N-terminal region of Factor H in MPGN II provides additional insight into the
      pathogenesis of this condition.

PMID- 16810289
TI  - Urinary protein markers in lupus nephritis: the need for concurrent calibration
      and discrimination statistics in predictive models.

PMID- 16810290
TI  - Generalized cholinergic heat urticaria induced by hemodialysis.

PMID- 16810293
TI  - p-Cresol for better or worse: but what are we measuring?

PMID- 16810294
TI  - UV increases the nuclear localization of apurinic/apyrimidinic endonuclease/redox
      effector factor-1 in human skin.

PMID- 16810295
TI  - Antigen specificity in subsets of mucous membrane pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) has several subsets based on target antigens
      recognized by their sera. MMP and ocular cicatricial pemphigoid (OCP) sera
      recognize beta4 integrin subunit, oral pemphigoid sera recognize alpha6 integrin
      subunit, and anti-epiligrin cicatricial pemphigoid sera recognize laminin 5. Our
      aim is to determine if autoantibodies in the sera of patients with MMP, OCP, and
      oral pemphigoid (OP) recognize only their target antigens, and to see if this
      specificity is maintained throughout the clinical course. An immunoblot assay
      using bovine gingival lysate was used as substrate. Fifteen MMP patients, eight
      with OCP, and 15 OP patients were studied before therapy and at multiple
      intervals during the clinical course. Absorption and blocking studies were
      performed to determine binding specificity. Sera of patients with MMP and OCP
      recognize only beta4 integrin subunit, and sera of OP patients recognize alpha6
      integrin throughout the clinical course. The sera of patients in the subsets of
      MMP described in this report show adherence and selectivity to target antigen
      during the entire clinical course, without crossover, interaction, or change.
      Hence, these subsets of MMP provide an excellent model to study clinical
      correlation with antigen and antibody specificity, in autoimmunity.

PMID- 16810296
TI  - All-trans retinoic acid antagonizes UV-induced VEGF production and angiogenesis
      via the inhibition of ERK activation in human skin keratinocytes.
AB  - Incident UV radiation leads to the upregulation of vascular endothelial growth
      factor (VEGF), a potent angiogenic factor, in human skin. However, the molecular
      basis of UV-induced angiogenesis in skin remains to be elucidated. In this study,
      we investigated the roles of UV exposure on cutaneous angiogenesis, its
      associated signaling mechanisms, and the effect of all-trans retinoic acid (tRA)
      on UV-induced vascularization, and VEGF expression. Using a human epidermal cell
      line, HaCaT, we found that UV induces VEGF mRNA and protein expression via the
      MAPK/ERK kinase-ERK1/2 (extracellular signal-regulated kinase 1/2) pathway but
      not via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, and that tRA
      pretreatment significantly inhibits UV-induced VEGF overexpression and ERK1/2
      activation. In human skin in vivo, we confirmed that skin vascularization
      significantly increased after a single exposure to UV, as was evidenced by a
      prominent increase in vessel size, vascular density, and in the cutaneous area
      occupied by vessels, and we found that these events are associated with VEGF
      upregulation. Topical pretreatment with tRA under occlusion inhibited not only UV
      induced VEGF upregulation and angiogenesis with a significant reduction of vessel
      density but also UV-induced ERK1/2 activation in human skin. Collectively, our
      data demonstrate that tRA inhibits the UV-induced angiogenic switch via
      downmodulation of ERK1/2 activation and consecutive VEGF overexpression. These
      findings may help us understand the molecular mechanisms that regulate skin
      angiogenesis due to UV exposure, and provide evidence of the potential of tRA in
      terms of preventing angiogenesis-associated skin damage following exposure to UV
      irradiation.

PMID- 16810297
TI  - Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis
      vulgaris and predispose individuals to atopic dermatitis.
AB  - Mutations in the filament aggregating protein (filaggrin) gene have recently been
      identified as the cause of the common genetic skin disorder ichthyosis vulgaris
      (IV), the most prevalent inherited disorder of keratinization. The main
      characteristics of IV are fine-scale on the arms and legs, palmar hyperlinearity,
      and keratosis pilaris. Here, we have studied six Irish families with IV for
      mutations in filaggrin. We have identified a new mutation, 3702delG, in addition
      to further instances of the reported mutations R501X and 2282del4, which are
      common in people of European origin. A case of a 2282del4 homozygote was also
      identified. Mutation 3702delG terminates protein translation in filaggrin repeat
      domain 3, whereas both recurrent mutations occur in repeat 1. These mutations are
      semidominant: heterozygotes have an intermediate phenotype most readily
      identified by palmar hyperlinearity and in some cases fine-scale and/or keratosis
      pilaris, whereas homozygotes or compound heterozygotes generally have more marked
      ichthyosis. Interestingly, the phenotypes of individuals homozygous for R501X,
      2282del4, or compound heterozygous for R501X and 3702delG, were comparable,
      suggesting that mutations located centrally in the filaggrin repeats are also
      pathogenic.

PMID- 16810298
TI  - Differences in expression of specific biomarkers distinguish human beard from
      scalp dermal papilla cells.
AB  - Androgen exposure stimulates the growth of beard hair follicles. The follicle
      dermal papilla appears to be the site of androgen action; however, the molecular
      mechanisms that regulate this process are not well understood. In an attempt to
      identify genes that contribute to the androgen-responsive phenotype, we compared
      gene expression patterns in unstimulated and androgen-treated cultured human
      dermal papilla cells isolated from beard (androgen-sensitive) and occipital scalp
      (androgen-insensitive) hair follicles. Through this analysis, we identified three
      genes that are expressed at significantly higher levels in beard dermal papilla
      cells. One of these genes, sfrp-2 has been identified as a dermal papilla
      signature gene in mouse pelage follicles. Two of these genes, mn1 and atp1beta1,
      have not been studied in the hair follicle. A fourth, fibulin-1d, was slightly
      upregulated in beard dermal papilla cells. The differences in the expression of
      these genes in cultured beard and scalp dermal papilla cells reflected similar
      differences in microdissected dermal papilla isolated from intact beard and scalp
      follicles. Our findings introduce potentially novel signaling pathways in dermal
      papilla cells. In addition, this study supports that cultured dermal papilla
      cells provide a cell-based model system that is reflective of the biology of in
      vivo hair follicle cells.

PMID- 16810299
TI  - Oxygen levels in normal and previously irradiated human skin as assessed by EF5
      binding.
AB  - The oxygen status of skin is a controversial topic. Skin is radiosensitive,
      suggesting it is well-oxygenated. However, it can be further sensitized with
      nitroimidazole drugs, implying that it is partially hypoxic. Skin oxygen levels
      are difficult to measure with either electrodes or the hypoxia-monitoring agent
      (3)H-misonidazole. For the latter, binding has previously been reported to be
      high in murine skin, but this could be attributed to either non-oxygen-dependent
      variations in nitroreductase activity, drug metabolism, and/or actual oxygen
      gradients. We obtained tumor and skin from patients given EF5, a 2-nitroimidazole
      tissue hypoxia monitor. We performed immunohistochemical studies using highly
      specific monoclonal antibodies for the hypoxia-dependent production of EF5 tissue
      adducts. Some tissue sections were counterstained using either Ki67 for
      proliferation or CD31 for vessels. We found that the human dermis is well
      oxygenated, the epidermis is modestly hypoxic and portions of some sebaceous
      glands and hair follicles are moderately to severely hypoxic. Normal and
      irradiated skin had similar oxygenation patterns. Control studies demonstrated
      that these observations are not due to tissue variations in nitroreductase
      activity. The importance of the highly heterogeneous distribution of oxygen in
      skin requires further study, but recent investigations suggest that skin hypoxia
      may have important clinical ramifications including mediating cellular
      transformation.

PMID- 16810300
TI  - Functional characterization of the epidermal cholinergic system in vitro.
AB  - The aim of this study was to analyze the influence of cholinergic and
      anticholinergic drugs on epidermal physiology using organotypic cocultures
      (OTCs). Blocking of all acetylcholine receptors (AChRs) by combined treatment
      with mecamylamine and atropine or treatment with strychnine (blocking
      alpha9nAChR) for 7-14 days resulted in a complete inhibition of epidermal
      differentiation and proliferation. Blockage of nicotinic (n)AChR with
      mecamylamine led to a less pronounced delay in epidermal differentiation and
      proliferation than blockage of muscarinic (m)AChR with atropine, evidenced by
      reduced epithelial thickness and expression of terminal differentiation markers
      like cytokeratin 2e or filaggrin. In OTCs treated with atropine, mecamylamine, or
      strychnine, we could demonstrate intracellular lipid accumulation in the lower
      epidermal layers, indicating a severely disturbed epidermal barrier. In addition,
      we observed prominent acantholysis in the basal and lower suprabasal layers in
      mecamylamine-, atropine-, and strychnine-treated cultures, accompanied by a
      decreased expression of cell adhesion proteins. This globally reduced cell
      adhesion led to cell death via intrinsic activation of apoptosis. In contrast,
      stimulation of nAChR and mAChR with cholinergic drugs resulted in a significantly
      thickened epithelium, accompanied by an improved epithelial maturation. In
      summary, we show that epidermal AChR are crucially involved in the regulation of
      epidermal homeostasis.

PMID- 16810301
TI  - Histone deacetylase inhibitors induce apoptosis with minimal viral reactivation
      in cells infected with Kaposi's sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells in
      patients with Kaposi's sarcoma and primary effusion lymphoma (PEL). The purpose
      of this study was to determine whether histone deacetylase inhibitors (HDAI)
      could induce apoptosis, with minimal viral replication, in cells latently
      infected with KSHV. Four HDAI (depsipeptide, suberoylanilide hydroxamic acid, MS
      275, and trichostatin A) were studied in two PEL B cell lines (BCBL-1, BC-3). As
      expected, histone hyperacetylation was readily induced in all PEL cells exposed
      to HDAI. HDAI also triggered KSHV reactivation in a time- and dose-dependent
      manner. Flow cytometric and transmission electron microscopic studies, however,
      revealed that reactivation occurred in only a minor percentage (3-14%) of treated
      cells. Importantly, and in contrast to viral reactivation, HDAI induced apoptotic
      cell death in a dose-dependent manner in a large percentage (up to 90%) of KSHV
      infected cells. In summary, all four HDAI tested induced histone hyperacetylation
      in all cells, KSHV reactivation in a minority of cells, and apoptotic cell death
      in a majority of cells latently infected with KSHV. These findings suggest that
      HDAI may be a therapeutic option for patients with KSHV-mediated diseases by
      rendering cells infected with KSHV susceptible to apoptosis.

PMID- 16810302
TI  - Rab33A: characterization, expression, and suppression by epigenetic modification.
AB  - Rab33A, a member of the small GTPase superfamily, is an X-linked gene that is
      expressed in brain, lymphocytes, and normal melanocytes, but is downregulated in
      melanoma cells. We demonstrate that in normal melanocytes Rab33A colocalizes with
      melanosomal proteins and that a constitutively active GTPase mutant suppresses
      their transport to the melanosomes. In the brain, Rab33A is present throughout
      the cortex, as well as in the hippocampal CA fields. A survey of melanocytic
      lesions demonstrated that aberrant downregulation of Rab33A is an early event
      that is already prevalent in melanocytes of giant congenital nevi. Analyses of
      bisulfite-modified DNA revealed that Rab33A is regulated by DNA methylation of a
      specific promoter region proximal to the transcription initiation site, and that
      suppression of Rab33A in melanoma cells recapitulates normal processes that
      control silencing of X-linked genes, but not tissue specific gene expression.
      This information is important for understanding carcinogenesis as well as other
      aberrant processes because Rab33A may have an important role in disorders
      involving X-chromosome-linked genes associated with vesicular transport.

PMID- 16810304
TI  - Direct injection of calcitriol or its analog into hyperplastic parathyroid glands
      induces apoptosis of parathyroid cells.
AB  - Hyperplasia of the parathyroid gland (PTG) is associated not only with excessive
      secretion of parathyroid hormone (PTH) but also with changes in the parathyroid
      cell (PTC) characteristics (i.e. hyperproliferative activity, and low contents of
      vitamin D and calcium-sensing receptors). Control of PTG hyperplasia is most
      important in the management of secondary hyperparathyroidism, but the advanced
      stage of hyperplasia is considered irreversible. In the present study, dialysis
      patients with PTG hyperplasia underwent direct injection of calcitriol or
      maxacalcitol (OCT) into the PTG. Ultrasonography showed that this treatment had
      significantly reduced PTG volume and tissue analysis using the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method and
      DNA electrophoresis indicated that cellular apoptosis had been induced. The
      mechanism of apoptosis was evaluated in detail in uremic rats fed a high
      phosphate diet. OCT or its vehicle was directly injected into the rats' PTGs. In
      the PTGs treated by OCT, there was a significantly increased number of TUNEL
      positive PTCs and DNA electrophoresis revealed the characteristic ladder pattern
      of DNA fragmentation, both findings indicative of apoptosis. There was also a
      significant upregulation of both vitamin D and Ca-sensing receptors in the PTCs
      and a clear shift of the Ca-PTH response curve to the left and downward. None of
      these findings was observed in the PTGs treated by vehicle. This novel treatment
      is successful in causing regression of PTG hyperplasia. Thus, it is expected to
      significantly reduce the PTH level and ameliorate the abnormal bone turnover and
      mineral metabolism.

PMID- 16810305
TI  - Influence of parathyroid mass on the regulation of PTH secretion.
AB  - In advanced uremia, parathyroid hormone (PTH) levels should be controlled at a
      moderately elevated level in order to promote normal bone turnover. As such, a
      certain degree of parathyroid gland (PG) hyperplasia has to be accepted. No
      convincing evidence of apoptosis or of involution of PG hyperplasia exists.
      However, even considerable parathyroid hyperplasia can be controlled when the
      functional demand for increased PTH levels is abolished. When 20 isogenic PG were
      implanted into one parathyroidectomized (PTX) rat normalization of Ca(2+) and PTH
      levels and normal suppressibility of PTH secretion by high Ca(2+) was obtained.
      Similarly, normal levels of Ca(2+) and PTH and suppressibility of PTH secretion
      were obtained when Eight isogenic PG from uremic rats were implanted into normal
      rats or when long-term uremia and severe secondary hyperparathyroidism (sec. HPT)
      was reversed by an isogenic kidney transplantation. Normalization of PTH levels
      after experimental kidney transplantation took place despite a persistent
      decrease of vitamin D receptor (VDR) mRNA and calcium sensing receptor (CaR) mRNA
      in PG. Thus, in experimental models PTH levels are determined by the functional
      demand and not by parathyroid mass, per se. When non-suppressible sec. HPT is
      present in patients referred to PTX, nodular hyperplasia with differences in gene
      expression between different nodules has been observed in most cases. An altered
      expression of some autocrine/paracrine factors has been demonstrated in the
      nodules. Enhanced expression of PTH-related peptide (PTHrP) has been demonstrated
      in PG from patients with severe secondary HPT. PTHrP has been shown to stimulate
      PTH secretion in vivo and in vitro. PTH/PTHrP receptor was demonstrated in the
      parathyroids. The low Ca(2+) stimulated PTH secretion was enhanced by 300% by
      PTHrP 1-40. The altered quality of the parathyroid mass and not only the
      increased parathyroid mass, per se, might be responsible for non-controllable
      hyperparathyroidism in uremia and after kidney transplantation.

PMID- 16810306
TI  - The parathyroid polyhormone hypothesis revisited.
AB  - The parathyroid polyhormone hypothesis holds that peptides derived from the
      metabolism of parathyroid hormone (PTH) (so-called C-terminal fragments) are
      themselves biologically active and that their effects are mediated by a novel 'C
      terminal receptor.' The evidence supporting these assertions is extensive but
      remains inconclusive. This Commentary focuses on in vivo pharmacology studies
      that provide information relevant to understanding the physiological significance
      of C-terminal fragments. The more recent studies of this sort provide compelling
      evidence that the bioactivity of C-terminal fragments is likely to become
      physiologically relevant in settings of secondary hyperparathyroidism. In this
      condition, circulating levels of C-terminal fragments greatly exceed those of
      PTH. There is convincing evidence that the hypocalcemic effect of C-terminal
      fragments results from direct actions on the skeleton that inhibit bone
      resorption. On the other hand, there are few if any results of in vivo studies
      suggesting a role for C-terminal fragments in more physiological settings, at
      least when parameters associated with systemic calcium homeostasis are assessed.

PMID- 16810307
TI  - Circulating PTH molecular forms: what we know and what we don't.
AB  - Circulating parathyroid hormone (PTH) molecular forms have been identified by
      three generations of PTH assays after gel chromatography or high-performance
      liquid chromatography fractionation of serum. Carboxyl-terminal (C) fragments
      missing the amino-terminal (N) structure of PTH(1-84) were identified first. They
      represent 80% of circulating PTH in normal individuals and up to 95% in renal
      failure patients. They are regulated by calcium (Ca) slightly differently than
      PTH(1-84), occurring in a relatively smaller proportion relative to the latter in
      hypocalcemia but in a much larger proportion in hypercalcemia. Synthetic C-PTH
      fragments do not bind to the PTH/PTHrP type I receptor and are not implicated in
      the classical biological effect of PTH(1-84). They bind to a different C-PTH
      receptor and exert biological actions on bone that are opposite to those of PTH(1
      84). The integrity of the distal C-structure appears to be important for these
      biological effects, and it is uncertain if all C-PTH fragments are intact up to
      position 84. A second category of C-PTH fragment has a partially preserved N
      structure. They are called non-(1-84) PTH or N-truncated fragments. They react in
      Intact (I)-PTH assays but not in PTH assays with a 1-4 epitope. They are acutely
      regulated by Ca(2+) concentration. They also exert similar hypocalcemic and
      antiresorptive effects but have 10-fold greater affinity for the C-PTH receptor
      compared to other C-PTH fragments. Even if they represent only 10% of all C-PTH
      fragments, they could be as relevant biologically. An N form of PTH other than
      PTH(1-84) has been identified in the circulation. It reacts very well in PTH
      assays with a 1-4 epitope but poorly in I-PTH assay with a 12-18 epitope. It is
      oversecreted in severe primary and secondary hyperparathyroidism and in
      parathyroid cancers. Its biological activity is still unknown. Overall, these
      studies suggest that PTH(1-84) and C-PTH fragments are regulated differently to
      exert opposite biological effects on bone via two different receptors. This may
      serve to control bone turnover and Ca concentration more efficiently.

PMID- 16810308
TI  - Basic and clinical aspects of parathyroid hyperplasia in chronic kidney disease.
AB  - Marked parathyroid hyperplasia develops in patients with chronic kidney disease,
      especially those with long dialysis vintage. Although progression of hyperplasia
      is associated with downregulation of vitamin D receptor and calcium-sensing
      receptor, initial abnormality that triggers and maintains parathyroid cell
      proliferation, as well the critical abnormality for the progression of diffuse
      hyperplasia to nodular hyperplasia, still remains to be elucidated. It is quite
      important for the optimal management of renal osteodystrophy to recognize the
      development of nodular hyperplasia, because the cells in nodular hyperplasia are
      usually resistant to medical therapy and further treatment of such patients often
      leads to vascular calcification. For this purpose, size and blood supply of
      enlarged parathyroid glands have been used as good clinical markers. Furthermore,
      we have recently shown that the serum fibroblast growth factor 23 level can be
      used for predicting refractory hyperparathyroidism. Once nodular hyperplasia
      develops in any of the enlarged parathyroid glands, such patients need to be
      treated by parathyroid intervention including percutaneous ethanol injection
      therapy. In addition, as direct vitamin D injection therapy has been shown to
      induce regression of hyperplasia, it may become possible to reverse or normalize
      established nodular hyperplasia if we can develop new agents with such effects in
      the near future.

PMID- 16810309
TI  - Insufficiency of PTH action on bone in uremia.
AB  - Abnormal bone turnover and mineral metabolism is observed in patients on
      dialysis. Secondary hyperparathyroidism (SHP) develops in response to mineral
      metabolism changes accompanying renal failure. As a factor of disease
      progression, the phenomenon of skeletal resistance to parathyroid hormone (PTH)
      is observed. With recent advances in the treatment of SHP, over-secretion of PTH
      can now be controlled. However, blood PTH levels 2 to 3 times higher than normal
      are considered necessary to maintain normal bone turnover in patients with renal
      failure. Various causes of skeletal resistance to PTH have been reported,
      including decrease in PTH receptor in osteoblasts, accumulation of 7-84 PTH
      fragment, and accumulation of osteoprotegerin. This skeletal resistance to PTH is
      not only a high-turnover bone accompanying SHP, but may also play a crucial role
      in the onset of low-turnover bone disease. We have produced a rat model of renal
      failure with normal level of PTH secretion and analyzed the bone of this model.
      Our results confirmed that bone turnover is lowered accompanying renal function
      impairment. We also found that this lowered bone turnover is improved by
      intermittent administration of PTH. In addition, PTH receptor gene expression is
      also decreased in low-turnover bone, as is observed in high-turnover bone
      disease. These findings confirm the presence of skeletal resistance to PTH in low
      turnover bone accompanying renal failure. Control of calcium, phosphorus, and PTH
      levels with the target to maintain normal bone turnover is important in
      maintaining the quality of life of patients on dialysis.

PMID- 16810310
TI  - Pathogenic mechanisms for parathyroid hyperplasia.
AB  - Parathyroid hyperplasia is the cause of parathyroid gland enlargement in kidney
      disease (KD). Hypocalcemia, hyperphosphatemia, and vitamin D deficiency are
      critical contributors to the worsening of the hyperplastic parathyroid growth
      induced by KD. Reproduction of the features of human KD in the 5/6 nephrectomized
      rat model has shown that 80% of the mitogenic signals induced by KD in
      parathyroid cells that are aggravated by either high phosphate (P) or low calcium
      (Ca) diets occurred within 5 days after the onset of KD. Enhanced parathyroid
      expression of the potent growth promoter transforming growth factor alpha
      (TGFalpha) and its receptor, the epidermal growth factor receptor (EGFR), was
      identified as the main cause of parathyroid hyperplasia in experimental KD.
      Indeed, administration of highly specific EGFR-tyrosine kinase inhibitors (TKI),
      which block downstream signaling from TGFalpha-activated EGFR, completely
      prevented high P- and low Ca-induced parathyroid hyperplasia in early KD, as well
      as the severe progression of high P-induced parathyroid growth in established
      secondary hyperparathyroidism, the latter characterized by marked TGFalpha and
      EGFR overexpression in the parathyroid glands. More importantly, the suppression
      of signals downstream from TGFalpha binding to EGFR with EGFR-TKI treatment also
      revealed that TGFalpha self-upregulation in the parathyroid glands is the main
      determinant of the severity of the hyperplastic growth, and that enhanced
      TGFalpha activation of EGFR mediates the reduction in parathyroid vitamin D
      receptor levels thereby causing resistance to both the antiproliferative and
      parathyroid hormone-suppressive properties of calcitriol therapy.

PMID- 16810311
TI  - Immunophenotypic overlap between adenoid cystic carcinoma and collagenous
      spherulosis of the breast: potential diagnostic pitfalls using myoepithelial
      markers.
AB  - Adenoid cystic carcinoma of the breast is a rare neoplasm whose cribriform
      architecture may mimic invasive cribriform carcinoma, cribriform ductal carcinoma
      in situ, and collagenous spherulosis. The diagnosis may be even more challenging
      in needle core biopsies. Immunohistochemical expression of p63 and c-kit
      distinguishes adenoid cystic carcinoma from invasive cribriform carcinoma and
      ductal carcinoma in situ. A formal comparison of the immunophenotype of adenoid
      cystic carcinoma to collagenous spherulosis has not been reported. Of concern is
      the overlap in myoepithelial markers between these two entities. Both may express
      S100, smooth muscle actin, and p63. This overlap may cause diagnostic confusion
      yet is under-emphasized in the literature. The expression profile of newer
      myoepithelial markers has not been studied in this setting. We evaluated smooth
      muscle actin, p63, calponin, smooth muscle myosin heavy chain, as well as c-kit,
      in nine cases of cribriform pattern adenoid cystic carcinoma of the breast in
      comparison to 12 cases of collagenous spherulosis. Both entities strongly
      expressed p63 and smooth muscle actin; in adenoid cystic carcinoma, the basaloid
      myoepithelial-like tumor cells expressed these markers, but the ductular
      epithelial cells did not. Neither calponin nor smooth muscle myosin heavy chain
      was expressed in adenoid cystic carcinoma but both were strongly expressed in
      collagenous spherulosis. Whereas the ductular epithelial cells of adenoid cystic
      carcinoma were positive for c-kit in all cases, collagenous spherulosis was
      negative for c-kit. Positive p63 expression by a cribriform breast lesion is not
      sufficiently specific to confirm a diagnosis of adenoid cystic carcinoma. A
      broader panel that includes calponin or smooth muscle myosin heavy chain and c
      kit is required to exclude collagenous spherulosis in settings in which the
      distinctive morphologic features that separate these entities are not
      conspicuously present. Reliance on p63 or smooth muscle actin alone poses a
      potential diagnostic pitfall in evaluating cribriform breast lesions.

PMID- 16810312
TI  - DNA mismatch repair and TP53 defects are early events in uterine carcinosarcoma
      tumorigenesis.
AB  - Growing molecular evidence shows that uterine carcinosarcomas are clonal tumors.
      The carcinoma component has a dominant effect in the aggressive clinical behavior
      of these tumors. Defective DNA mismatch repair affects up to 30% of endometrial
      adenocarcinomas. The frequency and importance of defective DNA mismatch repair in
      the histiogenesis of uterine carcinosarcomas remains controversial. We studied
      the pattern and frequency of defective DNA mismatch repair and TP53 alterations
      in the epithelial and mesenchymal components of 28 uterine carcinosarcomas. We
      found evidence of defective DNA mismatch repair in six cases (21%) with a
      concordance rate of 83% for carcinoma-sarcoma pairs (kappa=0.887, P<0.001). Lack
      of immunostaining for the MLH1 protein was demonstrated in both components in two
      of these tumors. TP53 defects were evaluated by 17p deletion analysis and p53
      immunostaining. Nineteen carcinoma (68%) and 18 sarcoma (64%) components had
      evidence of either TP53 allelic loss or p53 overexpression. These defects proved
      clonal in 76% of cases (kappa=0.602, P=0.003). Our results indicate that
      defective DNA mismatch repair and TP53 defects are common early events in
      carcinosarcoma tumorigenesis. The high rate of concordance for these molecular
      defects between the carcinoma and sarcoma components adds to existing molecular
      evidence that carcinosarcomas are clonal malignancies.

PMID- 16810313
TI  - Alteration of cytochrome oxidase subunit I labeling is associated with severe
      mitochondriopathy in NRTI-related hepatotoxicity in HIV patients.
AB  - Liver mitochondrial toxicity induced by nucleoside reverse transcriptase
      inhibitors (NRTI) in human immunodeficiency virus (HIV) patients has been
      associated with a wide range of liver involvement ranging from low-grade
      hepatotoxicity, asymptomatic lactacidemia to severe liver insufficiency, with
      massive steatosis and life-threatening lactic acidosis. Considerable efforts have
      been made in the last few years to establish clinical guidelines to avoid life
      threatening NRTI-associated lactic acidosis. However, the important issue of low
      grade NRTI-associated hepatotoxicity still needs to be unravelled since its
      natural history is largely unknown. We have recently reported a series of 13
      monoinfected HIV patients with low-grade NRTI-associated toxicity. Our results
      outlined the heterogeneity of NRTI-induced hepatotoxicity and raised the question
      of its diagnosis. The present study evaluates the expression of cytochrome
      oxidase (COX) subunits I and IV, encoded by mitochondrial and nuclear DNA,
      respectively, in NRTI hepatotoxicity. The aim of our study was to compare the
      detection rate of mitochondrial abnormalities of immunohistochemistry for COX
      subunit I with electron microscopy. COX subunit I and IV labeling was performed
      together with light microscopy and ultrastructural analysis in a series of 55
      liver biopsies from HIV monoinfected and HIV-hepatitis C virus coinfected
      patients. Clinical data were also recorded. Our major findings were: (i)
      decreased COX subunit I labeling is associated with severe ultrastructural
      mitochondrial alterations and may represent overt NRTI-induced mitochondrial
      cytopathy; (ii) mild ultrastructural damage associated with normal COX subunit I
      labeling is of unknown clinical significance. The results of the study suggest
      that COX subunit I labeling may be a valuable tool for the diagnosis of
      mitochondrial liver disease in HIV patients.

PMID- 16810314
TI  - Inhibition of cervical cancer cell growth in vitro and in vivo with lentiviral
      vector delivered short hairpin RNA targeting human papillomavirus E6 and E7
      oncogenes.
AB  - In this study, we investigated the suppressive effect of a short hairpin RNA
      delivered by a lentiviral vector (LV-shRNA) against human papillomavirus (HPV)
      type 18 E6 on the expression of the oncogenes E6 and E7 in cervical cancer HeLa
      cells both in vitro and in vivo. The LV-shRNA effectively delivered the shRNA to
      HeLa cells and lead to a dose-dependent reduction of E7 protein and the
      stabilization of E6 target proteins, p53 and p21. Low-dose infection of HeLa
      cells with LV-shRNA caused reduced cell growth and the induction of senescence,
      whereas a high-dose infection resulted in specific cell death via apoptosis.
      Transplant of HeLa cells infected with a low dose of LV-shRNA into Rag-/- mice
      significantly reduced the tumor weight, whereas transplant of cells infected with
      a high dose resulted in a complete loss of tumor growth. Systemic delivery of LV
      shRNA into mice with established HeLa cell lung metastases led to a significant
      reduction in the number of tumor nodules. Our data collectively suggest that
      lentiviral delivery is an effective way to achieve stable suppression of E6/E7
      oncogene expression and induce inhibition of tumor growth both in vitro and in
      vivo. These results encourage further investigation of this form of RNA
      interference as a promising treatment for cervical cancer.

PMID- 16810315
TI  - Large nucleotide-dependent movement of the N-terminal domain of the ClpX
      chaperone.
AB  - The ClpXP ATPase-protease complex is a major component of the protein quality
      control machinery in the cell. A ClpX subunit consists of an N-terminal zinc
      binding domain (ZBD) and a C-terminal AAA+ domain. ClpX oligomerizes into a
      hexamer with the AAA+ domains forming the base of the hexamer and the ZBDs
      extending out of the base. Here, we report that ClpX switches between a capture
      and a feeding conformation. ZBDs in ClpX undergo large nucleotide-dependent block
      movement towards ClpP and into the AAA+ ring. This motion is modulated by the
      ClpX cofactor, SspB. Evidence for this movement was initially obtained by the
      surprising observation that an N-terminal extension on ClpX is clipped by bound
      ClpP in functional ClpXP complexes. Protease-protection, crosslinking, and light
      scattering experiments further support these findings.

PMID- 16810317
TI  - An antagonistic function for Arabidopsis DCL2 in development and a new function
      for DCL4 in generating viral siRNAs.
AB  - Plants contain more DICER-LIKE (DCL) enzymes and double-stranded RNA binding
      (DRB) proteins than other eukaryotes, resulting in increased small RNA network
      complexities. Analyses of single, double, triple and quadruple dcl mutants
      exposed DCL1 as a sophisticated enzyme capable of producing both microRNAs
      (miRNAs) and siRNAs, unlike the three other DCLs, which only produce siRNAs.
      Depletion of siRNA-specific DCLs results in unbalanced small RNA levels,
      indicating a redeployment of DCL/DRB complexes. In particular, DCL2 antagonizes
      the production of miRNAs and siRNAs by DCL1 in certain circumstances and affects
      development deleteriously in dcl1 dcl4 and dcl1 dcl3 dcl4 mutant plants, whereas
      dcl1 dcl2 dcl3 dcl4 quadruple mutant plants are viable. We also show that viral
      siRNAs are produced by DCL4, and that DCL2 can substitute for DCL4 when this
      latter activity is reduced or inhibited by viruses, pointing to the
      competitiveness of DCL2. Given the complexity of the small RNA repertoire in
      plants, the implication of each DCL, in particular DCL2, in the production of
      small RNAs that have no known function will constitute one of the next
      challenges.

PMID- 16810316
TI  - Human SMC5/6 complex promotes sister chromatid homologous recombination by
      recruiting the SMC1/3 cohesin complex to double-strand breaks.
AB  - The structural maintenance of chromosomes (SMC) family of proteins has been
      implicated in the repair of DNA double-strand breaks (DSBs) by homologous
      recombination (HR). The SMC1/3 cohesin complex is thought to promote HR by
      maintaining the close proximity of sister chromatids at DSBs. The SMC5/6 complex
      is also required for DNA repair, but the mechanism by which it accomplishes this
      is unclear. Here, we show that RNAi-mediated knockdown of the SMC5/6 complex
      components in human cells increases the efficiency of gene targeting due to a
      specific requirement for hSMC5/6 in sister chromatid HR. Knockdown of the hSMC5/6
      complex decreases sister chromatid HR, but does not reduce nonhomologous end
      joining (NHEJ) or intra-chromatid, homologue, or extrachromosomal HR. The hSMC5/6
      complex is itself recruited to nuclease-induced DSBs and is required for the
      recruitment of cohesin to DSBs. Our results establish a mechanism by which the
      hSMC5/6 complex promotes DNA repair and suggest a novel strategy to improve the
      efficiency of gene targeting in mammalian somatic cells.

PMID- 16810318
TI  - Release of RASSF1C from the nucleus by Daxx degradation links DNA damage and
      SAPK/JNK activation.
AB  - Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) responds to a
      variety of stress stimuli and controls cell fates such as cell cycle entrance,
      apoptosis and senescence. Stimuli such as ultraviolet irradiation and chemical
      reagents that damage genomic DNA induce the activation of the SAPK/JNK signaling
      pathway. However, it is unclear how the signal arising in the nucleus owing to
      DNA damage is transmitted to SAPK/JNK in the cytoplasm. Here, we report that the
      nuclear components Daxx and Ras-association domain family 1C (RASSF1C) link DNA
      damage to SAPK/JNK activation in HeLa cells. In response to DNA damage, Daxx
      localized in promyelocytic leukaemia-nuclear bodies (PML-NBs) undergoes
      ubiquitination and degradation. RASSF1C, a tumor suppressor and newly identified
      binding partner of Daxx, is constitutively anchored by Daxx in PML-NBs but is
      released from the nucleus when Daxx is degraded. This released RASSF1C
      translocates to cytoplasmic microtubules and participates in the activation of
      SAPK/JNK. Our data define a novel mechanism by which the Daxx-RASSF1C complex in
      PML-NBs couples nuclear DNA damage to the cytoplasmic SAPK/JNK signaling pathway.

PMID- 16810319
TI  - HDAC6-p97/VCP controlled polyubiquitin chain turnover.
AB  - HDAC6 is a unique cytoplasmic deacetylase capable of interacting with ubiquitin.
      Using a combination of biophysical, biochemical and biological approaches, we
      have characterized the ubiquitin-binding domain of HDAC6, named ZnF-UBP, and
      investigated its biological functions. These studies show that the three Zn ion
      containing HDAC6 ZnF-UBP domain presents the highest known affinity for ubiquitin
      monomers and mediates the ability of HDAC6 to negatively control the cellular
      polyubiquitin chain turnover. We further show that HDAC6-interacting chaperone,
      p97/VCP, dissociates the HDAC6-ubiquitin complexes and counteracts the ability of
      HDAC6 to promote the accumulation of polyubiquitinated proteins. We propose that
      a finely tuned balance of HDAC6 and p97/VCP concentrations determines the fate of
      ubiquitinated misfolded proteins: p97/VCP would promote protein degradation and
      ubiquitin turnover, whereas HDAC6 would favour the accumulation of ubiquitinated
      protein aggregates and inclusion body formation.

PMID- 16810320
TI  - Calcium-dependent release of NO from intracellular S-nitrosothiols.
AB  - The paper describes a novel cellular mechanism for rapid calcium-dependent nitric
      oxide (NO) release. This release occurs due to NO liberation from S
      nitrosothiols. We have analysed the changes of NO concentration in acutely
      isolated pancreatic acinar cells. Supramaximal acetylcholine (ACh) stimulation
      induced a Ca(2+)-dependent increase in the fluorescence in the majority of cells
      loaded with the NO probe DAF-FM via a patch pipette. The ACh-induced NO signals
      were insensitive to inhibitors of calmodulin and protein kinase C but were
      inhibited by calpain antagonists. The initial part of the NO signals induced by
      10 muM ACh showed little sensitivity to inhibition of NO synthase (NOS); however,
      cell pretreatment with NO donors (increasing cellular S-nitrosothiol contents)
      substantially enhanced the initial component of NO responses. Pancreatic acinar
      cells were able to generate fast calcium-dependent NO responses when stimulated
      with physiological or supramaximal doses of secretagogues. Importantly, the
      source of this NO is the already available S-nitrosothiol store rather than de
      novo synthesis by NOS. A similar mechanism of NO release was found in dorsal root
      ganglia neurons.

PMID- 16810321
TI  - Combinatorial control of Arabidopsis proline dehydrogenase transcription by
      specific heterodimerisation of bZIP transcription factors.
AB  - Proline metabolism has been implicated in plant responses to abiotic stresses.
      The Arabidopsis thaliana proline dehydrogenase (ProDH) is catalysing the first
      step in proline degradation. Transcriptional activation of ProDH by hypo
      osmolarity is mediated by an ACTCAT cis element, a typical binding site of basic
      leucine zipper (bZIP) transcription factors. In this study, we demonstrate by
      gain-of-function and loss-of-function approaches, as well as chromatin
      immunoprecipitation (ChIP), that ProDH is a direct target gene of the group-S
      bZIP factor AtbZIP53. Dimerisation studies making use of yeast and Arabidopsis
      protoplast-based two-hybrid systems, as well as bimolecular fluorescence
      complementation (BiFC) reveal that AtbZIP53 does not preferentially form dimers
      with group-S bZIPs but strongly interacts with members of group-C. In particular,
      a synergistic interplay of AtbZIP53 and group-C AtbZIP10 was demonstrated by
      colocalisation studies, strong enhancement of ACTCAT-mediated transcription as
      well as complementation studies in atbzip53 atbzip10 T-DNA insertion lines.
      Heterodimer mediated activation of transcription has been found to operate
      independent of the DNA-binding properties and is described as a crucial mechanism
      to modulate transcription factor activity and function.

PMID- 16810322
TI  - X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in
      chromatin condensation.
AB  - Most serpins are associated with protease inhibition, and their ability to form
      loop-sheet polymers is linked to conformational disease and the human
      serpinopathies. Here we describe the structural and functional dissection of how
      a unique serpin, the non-histone architectural protein, MENT (Myeloid and
      Erythroid Nuclear Termination stage-specific protein), participates in DNA and
      chromatin condensation. Our data suggest that MENT contains at least two distinct
      DNA-binding sites, consistent with its simultaneous binding to the two closely
      juxtaposed linker DNA segments on a nucleosome. Remarkably, our studies suggest
      that the reactive centre loop, a region of the MENT molecule essential for
      chromatin bridging in vivo and in vitro, is able to mediate formation of a loop
      sheet oligomer. These data provide mechanistic insight into chromatin compaction
      by a non-histone architectural protein and suggest how the structural plasticity
      of serpins has adapted to mediate physiological, rather than pathogenic, loop
      sheet linkages.

PMID- 16810323
TI  - FGF-2 protects small cell lung cancer cells from apoptosis through a complex
      involving PKCepsilon, B-Raf and S6K2.
AB  - Patients with small cell lung cancer (SCLC) die because of chemoresistance.
      Fibroblast growth factor-2 (FGF-2) increases the expression of antiapoptotic
      proteins, XIAP and Bcl-X(L), and triggers chemoresistance in SCLC cells. Here we
      show that these effects are mediated through the formation of a specific
      multiprotein complex comprising B-Raf, PKCepsilon and S6K2. S6K1, Raf-1 and other
      PKC isoforms do not form similar complexes. RNAi-mediated downregulation of B
      Raf, PKCepsilon or S6K2 abolishes FGF-2-mediated survival. In contrast,
      overexpression of PKCepsilon increases XIAP and Bcl-X(L) levels and
      chemoresistance in SCLC cells. In a tetracycline-inducible system, increased S6K2
      kinase activity triggers upregulation of XIAP, Bcl-X(L) and prosurvival effects.
      However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not
      S6K1 mediates prosurvival/chemoresistance signalling.

PMID- 16810324
TI  - DNA damage-inducing agent-elicited gamma-secretase activity is dependent on
      Bax/Bcl-2 pathway but not on caspase cascades.

PMID- 16810325
TI  - A necrotic cell death model in a protist.
AB  - While necrotic cell death is attracting considerable interest, its molecular
      bases are still poorly understood. Investigations in simple biological models,
      taken for instance outside the animal kingdom, may benefit from less interference
      from other cell death mechanisms and from better experimental accessibility,
      while providing phylogenetic information. Can necrotic cell death occur outside
      the animal kingdom? In the protist Dictyostelium, developmental stimuli induced
      in an autophagy mutant a stereotyped sequence of events characteristic of
      necrotic cell death. This sequence included swift mitochondrial uncoupling with
      mitochondrial 2',7'-dichlorofluorescein diacetate fluorescence, ATP depletion and
      increased oxygen consumption. This was followed by perinuclear clustering of
      dilated mitochondria. Rapid plasma membrane rupture then occurred, which was
      evidenced by time-lapse videos and quantified by FACS. Of additional interest,
      developmental stimuli and classical mitochondrial uncouplers triggered a similar
      sequence of events, and exogenous glucose delayed plasma membrane rupture in a
      nonglycolytic manner. The occurrence of necrotic cell death in the protist
      Dictyostelium (1) provides a very favorable model for further study of this type
      of cell death, and (2) strongly suggests that the mechanism underlying necrotic
      cell death was present in an ancestor common to the Amoebozoa protists and to
      animals and has been conserved in evolution.

PMID- 16810330
TI  - Murine Wee1 plays a critical role in cell cycle regulation and pre-implantation
      stages of embryonic development.
AB  - Wee1 kinase regulates the G2/M cell cycle checkpoint by phosphorylating and
      inactivating the mitotic cyclin-dependent kinase 1 (Cdk1). Loss of Wee1 in many
      systems, including yeast and drosophila, leads to premature mitotic entry.
      However, the developmental role of Wee1 in mammals remains unclear. In this
      study, we established Wee1 knockout mice by gene targeting. We found that Wee-/-
      embryos were defective in the G2/M cell cycle checkpoint induced by gamma
      irradiation and died of apoptosis before embryonic (E) day 3.5. To study the
      function of Wee1 further, we have developed MEF cells in which Wee1 is disrupted
      by a tamoxifen inducible Cre-LoxP approach. We found that acute deletion of Wee1
      resulted in profound growth defects and cell death. Wee1 deficient cells
      displayed chromosome aneuploidy and DNA damage as revealed by gamma-H2AX foci
      formation and Chk2 activation. Further studies revealed a conserved mechanism of
      Wee1 in regulating mitotic entry and the G2/M checkpoint compared with other
      lower organisms. These data provide in vivo evidence that mammalian Wee1 plays a
      critical role in maintaining genome integrity and is essential for embryonic
      survival at the pre-implantation stage of mouse development.

PMID- 16810329
TI  - Mechanisms of malignant glioma immune resistance and sources of
      immunosuppression.
AB  - High grade malignant gliomas are genetically unstable, heterogeneous and highly
      infiltrative; all characteristics that lend glioma cells superior advantages in
      resisting conventional therapies. Unfortunately, the median survival time for
      patients with glioblastoma multiforme remains discouraging at 12-15 months from
      diagnosis. Neuroimmunologists/oncologists have focused their research efforts to
      harness the power of the immune system to improve brain tumor patient survival.
      In the past 30 years, small numbers of patients have been enrolled in a plethora
      of experimental immunotherapy Phase I and II trials. Some remarkable anecdotal
      responses to immune therapy are evident. Yet, the reasons for the mixed responses
      remain an enigma. The inability of the devised immunotherapies to consistently
      increase survival may be due, in part, to intrinsically-resistant glioma cells.
      It is also probable that the tumor compartment of the tumor-bearing host has
      mechanisms or produces factors that promote tumor tolerance and immune
      suppression. Finally, with adoptive immunotherapy of ex vivo activated effector
      cell preparations, the existence of suppressor T cells within them theoretically
      may contribute to immunotherapeutic failure. In this review, we will summarize
      our own studies with immunotherapy resistant glioma cell models, as well as cover
      other examined immunosuppressive factors in the tumor microenvironment and immune
      effector cell suppressor populations that may contribute to the overall immune
      suppression. An in-depth understanding of the obstacles will be necessary to
      appropriately develop strategies to overcome the resistance and improve survival
      in this select population of cancer patients.

PMID- 16810331
TI  - A novel nuclear-encoded mitochondrial poly(A) polymerase PAPD1 is a potential
      candidate gene for the extreme obesity related phenotypes in mammals.
AB  - People with obesity, especially extreme obesity, are at risk for many health
      problems. However, the responsible genes remain unknown in >95% of severe obesity
      cases. Our previous genome-wide scan of Wagyu x Limousin F2 cattle crosses with
      extreme phenotypes revealed a molecular marker significantly associated with
      intramuscular fat deposition. Characterization of this marker showed that it is
      orthologous to the human gene KIAA1462 located on HSA10p11.23, where a major
      quantitative trait locus for morbid obesity has been reported. The newly
      identified mitochondrial poly(A) polymerase associated domain containing 1
      (PAPD1) gene, which is located near this marker, is particularly interesting
      because the polymerase is required for the polyadenylation and stabilization of
      mammalian mitochondrial mRNAs. In the present study, both cDNA and genomic DNA
      sequences were annotated for the bovine PAPD1 gene and ten genetic markers were
      detected in the promoter and exon 1 region. Among seven markers assayed on
      approximately 250 Wagyu x Limousin F2 animals, two single nucleotide
      polymorphisms (SNPs) in the promoter region were significantly associated with
      intramuscular fat (P<0.05). However, there was a significant interaction (P<0.05)
      between a third SNP, which causes an amino acid change in coding exon 1, and each
      of these two promoter SNPs on intramuscular fat deposition. In particular, the
      differences between double heterozygous animals at two polymorphic sites and the
      slim genotype animals exceeded 2.3 standard deviations for the trait in both
      cases. Our study provides evidence for a new mechanism--the involvement of
      compound heterosis in extreme obesity, which warrants further examination.

PMID- 16810332
TI  - The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase
      (PARP-1) inhibitors.
AB  - BRCA1 and BRCA2 mutations are responsible for most familial breast carcinomas.
      Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient
      embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated
      that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA
      mutant cells with high specificity. Although these studies bring hope for BRCA
      mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer
      remains elusive. Here we present the first in vivo demonstration of PARP-1
      activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1
      inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells,
      mouse and human breast cancer cells. AG14361 was highly selective for BRCA1-/- ES
      cells; however, NU1025 and 3-aminobenzamide were relatively non-selective. In
      allografts of naive ES BRCA1-/- cells there was either partial or complete
      remission of tumors. However, in allografts of mouse, BRCA1-/- mammary tumors,
      there was no tumor regression or remission although a partial inhibition of tumor
      growth was observed in both the BRCA1-/- and BRCA1+/+ allografts. In human tumor
      cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of
      mammary tumors irrespective of their BRCA1 status. These results suggest that
      PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.

PMID- 16810333
TI  - The new portrait of mammary gland stem cells.

PMID- 16810334
TI  - Rebound effects following deliberate thought suppression: does PTSD make a
      difference?
AB  - This study was designed to examine the effects of deliberate suppression of
      trauma-related thoughts in 44 individuals who were PTSD+ and 26 individuals who
      were PTSD- following a motor vehicle accident (MVA). In an effort to resolve
      discrepancies in the literature, the PTSD- group was selected from the same help
      seeking population as the patient group. Measures included the percentage of MVA
      related thoughts, mood, perceived controllability of thoughts, and physiological
      arousal (heart rate, skin conductance, and two measures of facial EMG). Contrary
      to hypothesis, both PTSD+ and PTSD- groups showed a rebound in trauma-related
      thoughts following deliberate thought suppression. This rebound was associated
      with increases in negative affect, anxiety, and distress and diminished
      perceptions of controllability over thoughts. Examination of the physiological
      measures did not mirror the pattern noted for trauma-related thoughts, although
      the data suggest that suppression was associated with higher levels of frontalis
      EMG and possibly, reduced heart rate. The current study indicates that help
      seeking individuals who are distressed about their psychological state following
      a serious MVA will show a rebound in MVA-related thoughts, irrespective of PTSD
      diagnosis. Implications for the study of thought suppression as a potential
      maintaining factor for trauma-related problems are discussed, with suggestions
      for future research.

PMID- 16810335
TI  - Male rats show an indifference-avoidance response for increasing concentrations
      of the artificial sweetener sucralose.
AB  - Sucralose is a non-nutritive halogenated sucrose derivative that has been
      described by humans as tasting predominately sweet with little or no aftertaste.
      In this study we examined the preference for sucralose in adult male Sprague
      Dawley rats. A standard 24 hr two-bottle test was used to compare a wide range of
      sucralose concentrations (0.0003-10g/L; 0.8 MUM-25 mM) with water. The rats did
      not prefer sucralose to water at low concentrations (0.0003-0.3 g/L) and avoided
      sucralose at high concentrations (1-10g/L). Although there are many similarities
      in the taste preference of humans, mice, and rats, these results suggest that
      male rats do not prefer sucralose and avoid it at high concentrations. An
      awareness of the potential species differences in preference testing for novel
      sweeteners is critical for the taste and nutritional research communities.

PMID- 16810336
TI  - Normal Misbehavior: Scientists Talk about the Ethics of Research.
AB  - Those concerned with protecting the Integrity of science generally focus on the
      serious but rare infractions of falsification, fabrication, and plagiarism (FFP).
      While the violations of FFP are clear threats to the quality of scientific work
      and public trust in science, are they the behaviors that researchers themselves
      find most troubling? Noticing that scientists seldom are asked to report their
      perceptions of the behaviors that pose problems for the enterprise of science, we
      conducted six focus groups with researchers from major research universities. A
      total of 51 scientists participated in our focus-group discussions, which lasted
      from 1.5 to 2 hours each. We found that while researchers were aware of the
      problems of FFP, in their eyes misconduct generally is associated with more
      mundane, everyday problems in the work environment. These more common problems
      fall into four categories: the meaning of data, the rules of science, life with
      colleagues, and the pressures of production in science. Focus on the "normal
      misbehaviors" that are part of the ordinary life of researchers allows us to see
      the way the organization of science generates both compliance and deviance from
      ethical norms.

PMID- 16810337
TI  - Scientists' perceptions of organizational justice and self-reported misbehaviors.
AB  - Policymakers concerned about maintaining the integrity of science have recently
      expanded their attention from a focus on misbehaving individuals to
      characteristics of the environments in which scientists work. Little empirical
      evidence exists about the role of organizational justice in promoting or
      hindering scientific integrity. Our findings indicate that when scientists
      believe they are being treated unfairly they are more likely to behave in ways
      that compromise the integrity of science. Perceived violations of distributive
      and procedural justice were positively associated with self-reports of
      misbehavior among scientists.

PMID- 16810338
TI  - Pregnancy weight gain: marmoset and tamarin dads show it too.
AB  - Paternal behaviour is critical for the survival of offspring in many monogamous
      species. Common marmoset (Callithrix jacchus) and cotton-top tamarin (Saguinus
      oedipus) fathers spend as much or more time caring for infants than mothers.
      Expectant males of both species showed significant increases in weight across the
      pregnancy whereas control males did not (five consecutive months for marmoset
      males and six months for cotton-top tamarin males). Expectant fathers might be
      preparing for the energetic cost of fatherhood by gaining weight during their
      mate's pregnancy.

PMID- 16810339
TI  - Inflammatory activity and anticardiolipin antibodies during tibolone treatment of
      healthy postmenopausal women.
AB  - The aim of the study was to investigate the inflammatory activity and
      anticardiolipin antibodies (Acl) during tibolone administration. Twenty seven
      clinically healthy postmenopausal women were included in the study and were
      divided into two groups: 16 women (mean age 56.4 +/- 4.6 years) who received
      tibolone at a dose of 2.5 mg/day for 6 months and an untreated control group (n =
      11, mean age 54.8 +/- 4.0 years). Acl of IgG and IgM isotype, and C-reactive
      protein (CRP) were determined at baseline, 1, 3, and 6 months after treatment.
      Acl did not change during tibolone treatment, while CRP increased significantly
      at the 1st, 3rd, and 6th month compared with that at the baseline values. These
      preliminary data indicate that tibolone administration does not induce increase
      in Acl. This may counterbalance the adverse influence on CRP.

PMID- 16810340
TI  - Analgesic activity of the methanolic extract and total alkaloids of Glaucium
      paucilobum.
AB  - The species of Glaucium have been used in Iranian herbal medicine as laxative,
      hypnotic, narcotic, and antidiabetic agents and also in the treatment of
      dermatitis. The analgesic activity of the aerial parts of Glaucium Freyn
      (Papaveraceae), a native plant of Iran, were studied using formalin, hot plate,
      and writhing tests in rodents. The methanolic extract and total alkaloids of
      Glaucium paucilobum caused graded inhibition of both phases of formalin-induced
      pain. In the hot plate test, i.p. administration of G. paucilobum extract at the
      doses of 50-90 mg/kg and total alkaloids at the dose of 10-60 mg/kg significantly
      raised the pain threshold at an observation time of 30 min in comparison with
      control (p < 0.001). In the writhing test, the extract at the doses of 30-90
      mg/kg and total alkaloids at the doses of 10-60 mg/kg produced a significant
      decrease in the number of writhings in comparison with the control group (p <
      0.001). The methanolic extract and total alkaloids of G. paucilobum, at
      antinociceptive doses, did not affect the motor coordination of animals when
      assessed in the rotarod model. The results showed that analgesic activity of this
      plant may be related partly to the alkaloids.

PMID- 16810341
TI  - Phenolic components and antioxidant activity of Fernblock, an aqueous extract of
      the aerial parts of the fern Polypodium leucotomos.
AB  - Fernblock, an aqueous extract of the aerial parts of the fern Polypodium
      leucotomos, used as raw material for topical and oral photoprotective
      formulations, was fractioned by HPLC and the main components with antioxidant
      capability were identified by means of UV spectra, electrochemical detection, and
      MSn. Phenolic compounds were identified as 3,4-dihydroxybenzoic acid, 4
      hydroxybenzoic acid, vanillic acid, caffeic acid, 4-hydroxycinnamic acid, 4
      hydroxycinnamoyl-quinic acid, ferulic acid, and five chlorogenic acid isomers.
      Total ferric antioxidant capacity (FRAP) of HPLC eluted fractions was measured.
      The results suggest that the herein identified compounds support, at least
      partially, the antioxidant and radical scavenging capacities of Fernblock.

PMID- 16810342
TI  - Plasma pooling to expedite bioequivalence estimation of rifampicin in fixed dose
      combinations.
AB  - Rifampicin has been found to be one of the most important antitubercular drugs;
      however, variable bioavailability of rifampicin in some fixed dose combinations
      (FDCs) as well as separate formulations has been reported in the literature. This
      resulted in proper evaluation of FDCs with standard protocol for bioequivalence
      trials. Earlier, plasma pooling as a rapid method for bioequivalence assessment
      of rifampicin in FDCs was proposed from our laboratory. Results obtained after
      pooled plasma sample analysis were compared with those from the individual plasma
      sample analysis. Case studies from our laboratories further validate and support
      the use of plasma pooling method as a faster and cost effective tool for
      bioequivalence assessment of rifampicin in FDCs, which will be useful in order to
      speed up the registration and approval of good quality FDCs.

PMID- 16810343
TI  - Diabetes, insulin, and risk of cancer.
AB  - Up to now, the studies involving diabetes mellitus and malignancies show
      controversial results: Many of them have found incidences of malignancies that
      were comparable or even lower than those in nondiabetic subjects; others conclude
      that diabetes mellitus is linked to a higher incidence of malignancies and/or a
      predictor of mortality from cancer. Insulin and its precursors, pro- and pre
      proinsulin, have been shown to have some homology to the insulin-like growth
      factors, but, moreover they have some affinity to bind at receptors of the tumor
      growth factor and some hybrids too. Hence, an association between diabetes
      mellitus, insulin, hyperinsulinaemia, and carcinogenesis appears plausible. On
      the other hand, diabetes mellitus can influence different hormone levels. In some
      tumor entities, such as prostate carcinoma, this effect can somewhat
      counterbalance the direct mitogene effect of insulin and its precursors. All in
      all, as a result of the complexity of these mechanisms and the differences
      between the tumor entities, the question whether diabetes mellitus is associated
      with an increased or a reduced risk for the development and in respect of the
      prognosis of cancer cannot be answered. The only way to give some answer is to
      focus on specific tumor entities: It seems that diabetes mellitus and/or
      hyperglycaemia are independent risk factors and/or predictors at least in respect
      of cancer of the colon, pancreas, female breast, endometrium, and, in men, of the
      liver and bladder. However, most of these data were assessed in patients with
      type 2 diabetes mellitus. This makes it highly questionable whether the data can
      easily be transferred to patients with type 1 diabetes. Moreover, additional
      potential limitations are that most of the studies do not focus on the treatment
      modality or the race of participants. In conclusion, up to the present, we have
      an increased risk for some and a reduced risk for other tumor entities, but
      still, we cannot give the general answer.

PMID- 16810344
TI  - Therapeutic potential of cannabinoid receptor ligands: current status.
AB  - There are at least two types of cannabinoid receptors, CB1 also named CNR1 and
      CB2 also named CNR2, both coupled to G proteins. CB1 receptors exist primarily on
      central and peripheral neurons. CB2 receptors are present mainly on immune cells.
      Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been
      discovered, the most important being arachidonoyl ethanolamide (anandamide), 2
      arachidonoyl glycerol (2-AG), and 2-archidonyl glyceryl ether. Following their
      release, endocannabinoids are removed from the extracellular space and then
      degraded by intracellular enzymic hydrolysis. CB1/CB2 agonists are already used
      clinically as antiemetic or to stimulate appetite. Potential therapeutic uses of
      cannabinoid receptor agonists include the management of multiple sclerosis,
      spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma,
      vasodilatation that accompanies advanced cirrhosis, and cancer.

PMID- 16810345
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: ABT-510, adalimumab, alefacept,
      alemtuzumab, AMG-531, anakinra, armodafinil, asenapine maleate, atazanavir
      sulfate, atorvastatin; Bortezomib, bosentan; CEB-1555, cetuximab, ciclesonide,
      clodronate, CT-011; Darifenacin hydrobromide, desloratadine; E-7010, ecallantide,
      eculizumab, efalizumab, eltrombopag, erlotinib hydrochloride, eslicarbazepine
      acetate, eszopiclone, ezetimibe; Febuxostat, fosamprenavir calcium, fulvestrant;
      Gefitinib, genistein; Haemophilus influenzae B vaccine, human papillomavirus
      vaccine; Imatinib mesylate, insulin glargine; Lenalidomide, liposomal cisplatin;
      MAb G250, mapatumumab, midostaurin, MP4, mycophenolic acid sodium salt;
      Natalizumab, neridronic acid, NSC-330507; Oblimersen sodium, ofatumumab,
      omalizumab, oral insulin, oregovomab; Paliperidone, parathyroid hormone (human
      recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa
      2b/ribavirin, pegylated arginine deiminase 20000, pemetrexed disodium,
      pimecrolimus, pitavastatin, pneumococcal 7-valent conjugate vaccine, prasterone,
      pregabalin, pumosetrag hydrochloride; Recombinant malaria vaccine, retigabine,
      rivaroxaban, Ro-26-9228, romidepsin, rosuvastatin calcium, rotavirus vaccine; SGN
      30, sitaxsentan sodium, solifenacin succinate, sorafenib, sunitinib malate;
      Tadalafil, tegaserod maleate, temsirolimus, TER-199, tifacogin, tiludronic acid,
      tiotropium bromide; Vildagliptin, VNP-40101M, vorinostat; YM-150, yttrium 90
      (90Y) ibritumomab tiuxetan; Zanolimumab, zoledronic acid monohydrate.

PMID- 16810346
TI  - Abstracts of the 2nd World Veterinary Orthopaedic Congress and the 33rd Annual
      Conference of the VOS. February 25-March 4, 2006. Keystone, Colorado, USA.

PMID- 16810347
TI  - The use of radiofrequency energy during arthroscopic surgery and its effects on
      intraarticular tissues.
AB  - The use of radiofrequency (RF) energy has become very popular in human and
      veterinary arthroscopic surgery since the late 1990s. Both monopolar and bipolar
      RF units are available. Application of RF energy to joint capsular tissue leads
      to immediate tissue shrinkage that is both power and temperature dependent.
      Changes in joint capsular tissue have been noted at temperatures greater than 65
      degrees C. Treatment of articular cartilage with RF energy leads to immediate
      chondrocyte damage. This damage is also power and temperature dependent and is
      observed at temperatures as low as 45 degrees C. Caution should be used when
      applying RF energy within a joint to prevent or minimize articular cartilage
      injury.

PMID- 16810348
TI  - Augmentation of intertransverse process lumbar fusion.
AB  - Spinal fusion surgery for alleviation of intractable lower back pain in humans is
      currently a primary therapeutic technique, with failure rates averaging between 5
      to 35%. Implanted and external source-based electrical stimulation devices have
      been investigated in an attempt to increase osteogenesis at the fusion site in an
      attempt to reduce spinal fusion failure rates. The purpose of our study was to
      evaluate the efficacy of two co-processor systems and an additional system with
      an SIS generation field at 15.8 mA (rms) using biomechanical, dual-energy X-ray
      absorptiometry (DXA), and histomorphometric analyses, in rabbits following
      dorsolateral (= posteriolateral [in humans]) spinal fusion. Fifty-six male New
      Zealand White underwent bilateral lumbar spinal fusion by performing
      decortication of the transverse processes of lumbar vertebrae four and five with
      placement of autogenic cancellous bone graft harvested from the ilial wings. Four
      study groups were designated based on the type of IES device used for stimulation
      or as a control. Eight weeks after surgery all subjects were sacrificed and the
      quality and strength of the fusion masses were compared using radiographic,
      biomechanical, histomorphometry, and qualitative histological evaluation. While
      some variation existed within and between groups, Group 2 showed a significant
      improvement in all parameters measured as compared to the control group (P <
      0.05). The use of adjunct non-invasive surface IES for improving bony fusion
      rates for patients undergoing lumbar spinal fusion is supported by this study.

PMID- 16810349
TI  - The measurement of ground reaction force in dogs trotting on a treadmill: an
      investigation of habituation.
AB  - We studied the time necessary to obtain reliable kinetic data from healthy dogs
      trotting on a treadmill. Ten adult male Malinois Belgian Shepherd dogs were made
      to trot on an instrumented treadmill to record the ground reaction force for the
      entire body and to determine the vertical force variables (peak [PFz], impulse
      [IFz], stride time [Str], peak time [Tz] and contact time [Ct]). Data were
      collected from each dog, during three sequences per day, on three consecutive
      days. In order to determine the contribution of the sequence, day of measurement,
      and dog factors and the percentage of variance attributable to dogs, data were
      analyzed with a linear mixed model. The curve shapes were similar to those
      obtained with a floor-mounted force platform. Intra-dog coefficients of variation
      were between 1.57 and 3.46%. Inter-dog coefficients of variation were between
      4.18 and 7.82%. A sequence effect was not noted. Each day had a significant
      effect on all of the data. All variables differed significantly from the first
      day compared to the other days. However there was not any difference between days
      2 and 3. The percentage of the total variance attributable to dogs ranged from 37
      to 88%. The coefficients of variation were lower than those obtained with common
      protocols. The treadmill locomotion remained consistent during a single session.
      Even if interday variation needs to be accounted for, reliable data can still be
      obtained after a single training session. The majority of the variation was
      attributable to the dog. An instrumented treadmill may be used for kinetic
      analysis.

PMID- 16810351
TI  - Ex vivo comparison of a novel tapered-sleeve and traditional full-limb
      transfixation pin cast for distal radial fracture stabilization in the horse.
AB  - Distal radial fractures in adult horses are examples of long-bone fractures that
      are not always amenable to internal fixation. These fractures are often open,
      contaminated, severely comminuted, and located adjacent to the antebrachiocarpal
      joint. There have been few studies to improve upon the methods of stabilization
      of this type of fracture. External coaptation incorporating transfixation pins is
      one method that has been used to stabilize distal radial fractures in horses (1
      3). The purpose of this preliminary study was to compare the load to failure in
      simulated weight-bearing of a novel tapered-sleeve transfixation pin cast (TSTPC)
      (4) with the traditional transfixation pin cast (TPC) in an ex vivo distal radial
      fracture model. Ten adult equine cadaveric forelimbs were randomly placed into a
      TPC group (n = 5) or a TSTPC group (n = 5). An oblique distal radial osteotomy
      was created prior to application of fibreglass cast material. The limbs were
      loaded in a single cycle to failure in simulated weight-bearing using an axial
      load. The mean load to failure for the TSTPC group (35,814 N) was significantly
      greater than in the TPC group (22,344 N) (p = 0.003). Tapered sleeves in
      conjunction with TPC warrant further investigation because they may prolong the
      life of the fixation, prevent or diminish fractures through the pin sites, and
      increase the load capacity of external coaptation used to stabilize equine
      fractures.

PMID- 16810350
TI  - Villonodular synovitis in the dog: a report of four cases.
AB  - Four cases of villonodular synovitis were diagnosed by histopathology. All four
      dogs were treated medically with either carprophen or a combination of carprophen
      and glucosamine complex (Cosequin). In three of the dogs the condition improved
      significantly, and these dogs returned to normal workload.

PMID- 16810352
TI  - The evaluation of extracorporeal shock wave therapy on collagenase induced
      superficial digital flexor tendonitis.
AB  - Extracorporeal shock wave therapy (ESWT) is being used to treat desmitis and
      tendonitis in horses. This paper compares the clinical, ultrasonographic and
      histological characteristics of ESWT treated collagenase induced superficial
      digital flexor tendon (SDFT) lesions, versus untreated controls. This blinded
      study utilizes six mature, healthy horses where bilateral forelimb SDFT lesions
      were induced. One forelimb was treated while the other served as an untreated
      control. Three shock wave treatments were administered at three week intervals.
      At weekly intervals, ultrasonograms were used to measure: 1) percentage lesion at
      the maximum injury zone (MIZ), 2) the grey scale of the SDFT at the MIZ, 3) the
      percentage disruption of the longitudinal fibres at the MIZ. The data were also
      summed from 8-20 cm distal to the accessory carpal bone. Measurements of the
      external width of the SDFT were obtained through the study period. Examinations
      were performed on four occasions to evaluate heat, response to palpation,
      presence/character of swelling over the SDFT, and lameness. At the completion of
      the study all tendons were evaluated histologicalally. The lesion size, grey
      scale, and longitudinal fibre disruption at the MIZ, and sum of each variable
      changed significantly over time, however, there was no difference between treated
      and control groups. Histopathology showed increased neovascularization in treated
      tendons (p = 0.001). When compared to untreated controls, ESWT did not change the
      ultrasonographic appearance of the tendons. However, it did increase
      neovascularization.

PMID- 16810353
TI  - Inclusion of marbofloxacin in PMMA orthopaedic cement: an in vitro experimental
      study.
AB  - This in vitro experimental study investigated the feasibility for marbofloxacin,
      a veterinary fluoroquinolone antibiotic, to retain its antibacterial activity
      after its inclusion in polymethylmethacrylate (PMMA) cement. The assays were
      conducted on gelose cultures of various types of bacteria isolated from canine
      spontaneous osteomyelitis. The efficiency of the antibiotics was assessed by
      using an antibiogram method. Resistance of marbofloxacin to the temperature
      observed during PMMA polymerization, antimicrobial effect of galenic, useful
      concentrations and comparison with gentamicin (reference antibiotic for this use)
      were evaluated. Marbofloxacin retained its antimicrobial activity after being
      heated to high temperatures reached during polymerization. The more effective
      galenic form to incorporate into the PMMA monomer was the marbofloxacin powder
      and the appropriate concentration was 1/40 degrees . In this experiment,
      marbofloxacin included in PMMA showed a good antimicrobial activity; however this
      activity was lower than gentamicin added to PMMA on Gram + and Pseudomonas
      bacteria.Therefore, it seems useful to incorporate marbofloxacin to PMMA cement
      to treat, or to prevent, osteomyelitis associated with marbofloxacin sensitive
      bacteria. Nevertheless, the development of a marbofloxacin-PMMA cement requires
      further evaluation, especially pharmacological, biomechanical and clinical.

PMID- 16810354
TI  - Isolated medial meniscal tear in a Border Collie.
AB  - A three-year-old, female Border Collie was successfully treated for an isolated,
      torn, medial meniscus by arthroscopic meniscal tear resection. The dog returned
      to agility competition without recurrence of lameness.

PMID- 16810355
TI  - Carpal derangement and associated carpal valgus in a dog.
AB  - This case report describes derangement of the numbered carpal bones resulting in
      a valgal growth deformity in the right carpus of a seven-month-old dog.
      Radiographic assessment of the right carpus revealed abnormalities in the size
      and shape of the numbered carpal bones and carpal valgus. Surgical correction of
      the growth deformity was planned by partial carpal arthrodesis; however medial
      collateral laxity associated with the carpal valgus necessitated a pancarpal
      arthrodesis to achieve correct limb alignment.

PMID- 16810356
TI  - Fibrotic contracture of the canine infraspinatus muscle: pathophysiology and
      prevention by early surgical intervention.
AB  - Fibrotic contracture of the canine infraspinatus muscle (FCIM) is considered a
      rare musculotendineous disorder mainly affecting hunting dogs. After an acute
      onset of a painful non-weight bearing lameness, the initial pain and lameness
      improve over a period of one to four weeks, after which a characteristic
      circumducted gait abnormality develops in the forelimb. The initial injury to the
      infraspinatus muscle is not fully recognized or correctly interpreted in most
      cases, at least not with regard to its potential as a precursor of myopathy and
      FCIM. A mixed breed hunting dog developed an acute and extremely painful swelling
      of the infraspinatus muscle. The injury was easily recognized during clinical
      examination. The clinical signs were interpreted as an osteo-fascial compartment
      syndrome (OFCS) of the infraspinatus muscle. Immediate surgical decompression of
      the osteo-fascial compartment to prevent development of FCIM was undertaken. The
      histopathological and immunohistochemical examinations of the injured
      infrapinatus muscle revealed tissue changes that indicated acute muscle rupture,
      without any signs of an initiating degenerative process. On the day following
      surgery the dog was fully weight bearing. Restriction of activity for four weeks
      was recommended. Eight months after the initial injury, the dog had completely
      recovered and had full days of vigorous exercise and hunting activity without any
      apparent lameness. The findings in this case suggested that the infraspinatus
      muscle may be considered to be an osteo-fascial compartment in dogs and must be
      added to the list of compartments that may pose a potential risk for OFCS in the
      canine extremity.

PMID- 16810357
TI  - [Assessment of the national health plan. 1968].

PMID- 16810358
TI  - [Policy and planning: the Leonel Miranda Health Plan].

PMID- 16810359
TI  - [The "1967 National Health Plan" and today's "prepaid health plans": anything in
      common?].

PMID- 16810360
TI  - [Sistematical mass roentgenphotography: economical unviability and eventual
      danger regarding exposure to radiations. 1976].
AB  - The invention of roentgenphotography by Manoel de Abreu and its consequent
      widespread use in Brasil are described. Due to legal requirements, children,
      young people and pregnant womem are submitted repeatedly and, very often, to
      unnecessary examinations. After the atomic explosions of Hiroshima and Nagasaki
      and the knowledge that even minimum dosis of ionizing radiation can cause serious
      somatic and genetic risks, the widespread use of abreugraphy became cause of
      serious concern for Public Health workers, since its advantages are outnumbered
      by its cost and by the risk it offers to those submitted to this type of
      examination. According to recent litterature on the subject and following
      specific recommendations of the World Health Organization, abolition of
      widespread use of abreugraphy is proposed, with the elimination of the Brazilian
      legal requirements which make this method of examination mandatory in many
      situations.

PMID- 16810361
TI  - [Health technologies and the fine balance between risks and benefits].

PMID- 16810362
TI  - [The case detection of tuberculosis through mass x-ray examination: the cost and
      implications].

PMID- 16810364
TI  - Air pollution effects on myocardial infarction.
AB  - OBJECTIVE: Myocardial infarction is an acute and severe cardiovascular disease
      that generally leads to patient admissions to intensive care units and few cases
      are initially admitted to infirmaries. The objective of the study was to assess
      whether estimates of air pollution effects on myocardial infarction morbidity are
      modified by the source of health information. METHODS: The study was carried out
      in hospitals of the Brazilian Health System in the city of Sao Paulo, Southern
      Brazil. A time series study (1998-1999) was performed using two outcomes:
      infarction admissions to infirmaries and to intensive care units, both for people
      older than 64 years of age. Generalized linear models controlling for seasonality
      (long and short-term trends) and weather were used. The eight-day cumulative
      effects of air pollutants were assessed using third degree polynomial distributed
      lag models. RESULTS: Almost 70% of daily hospital admissions due to myocardial
      infarction were to infirmaries. Despite that, the effects of air pollutants on
      infarction were higher for intensive care units admissions. All pollutants were
      positively associated with the study outcomes but SO2 presented the strongest
      statistically significant association. An interquartile range increase on SO2
      concentration was associated with increases of 13% (95% CI: 6-19) and 8% (95% CI:
      2-13) of intensive care units and infirmary infarction admissions, respectively.
      CONCLUSIONS: It may be assumed there is a misclassification of myocardial
      infarction admissions to infirmaries leading to overestimation. Also, despite the
      absolute number of events, admissions to intensive care units data provides a
      more adequate estimate of the magnitude of air pollution effects on infarction
      admissions.

PMID- 16810363
TI  - [The 2004 Pelotas birth cohort: methods and description].
AB  - OBJECTIVE: To describe a birth cohort which started in 2004, aiming to assess pre
      and perinatal conditions of the newborns, infant morbimortality, early life
      characteristics and outcomes, and access, use and financing of health care.
      METHODS: All children born in the urban area of Pelotas and Capao do Leao
      municipalities (Southern Brazil) in 2004 were identified and their mothers
      invited to join the study. In the first year of the study the children were seen
      at birth, at three and 12 months of age. These visits involved the application of
      a questionnaire to the mothers including questions on health; life style; use of
      health services; socioeconomic situation; estimation of gestational age;
      anthropometric measurements on the newborn (weight, length, head, chest and
      abdominal circumferences); anthropometric measurements on the mother (weight and
      height) and assessment of infant development. RESULTS: Out of the eligible
      infants (4,558), more than 99% were recruited to the study at birth. Follow-up
      rates were 96% at three months and 94% at 12 months of age. Among the initial
      results we highlight the following. Infant mortality rate was 19.7 per thousand,
      with 66% of infant deaths occurring in the neonatal period. There were
      frequencies of 15% premature babies and 10% low birthweight. Cesarean sections
      represented 45% of deliveries. CONCLUSIONS: The third Pelotas birth cohort showed
      an infant mortality rate similar to that of 11 years ago, with most deaths
      occurring in the neonatal period. The rates of prematurity and cesarean sections
      increased substantially.

PMID- 16810365
TI  - [Prevalence of dyspepsia and associated sociodemographic factors].
AB  - OBJECTIVE: To assess prevalence of dyspepsia and distribution of dyspepsia and
      frequent dyspepsia in subgroups of adults (20 years and older) according to their
      demographic and socioeconomic characteristics. METHODS: A cross-sectional
      population-based study was carried out comprising 3,934 subjects living in
      Pelotas, Southern Brazil, from October 1999 to January 2000. Data was collected
      through household interviews. Dyspepsia was defined as epigastric pain or
      discomfort associated or not with nausea in the previous year, according to Rome
      I and Rome II criteria. Frequent dyspepsia was defined as more than six dyspepsia
      episodes in the previous year and/or nausea, at least once a month. These
      outcomes were analyzed according to age, gender, skin color, educational level,
      per capita income and marital status. Data analysis was carried out through
      Pearson Chi-square test for categorical variables and linear trend test, when
      applicable. RESULTS: The prevalence of dyspepsia was 44.4% and frequent
      dyspepsia, 27.4%. The prevalences of reflux-like, ulcer-like, dysmotility-like
      and unspecific dyspepsia subtypes were 19.4%, 6.3%, 13.9%, and 16.6%,
      respectively. The prevalences of these subtypes of frequent dyspepsia were 14.7%,
      4.9%, 11.2% and 6.8%, respectively. Prevalences among women were 50% higher. Low
      income young people seemed to be more affected by dyspeptic symptoms. The
      analysis according to Rome II criteria showed prevalences of 15.9% and 7.5% for
      dyspepsia and frequent dyspepsia, respectively. CONCLUSIONS: Dyspepsia and
      frequent dyspepsia were prevalent problems in the studied population. Most people
      could be classified in more than one subgroup of dyspepsia.

PMID- 16810366
TI  - [Factors associated with pulmonary disease among the elderly].
AB  - OBJECTIVE: To investigate the prevalence of reported pulmonary disease among
      elderly subjects, according to sociodemographic and economic characteristics,
      lifestyle, physical mobility, and health status. METHODS: This was a cross
      sectional population-based study that included 1,957 elderly subjects (aged 60
      and over). Information was collected by means of interviews. Subjects were
      selected using a two-stage probabilistic, stratified, cluster sampling strategy
      in six municipalities in the State of Sao Paulo between 2001 and 2002.
      Descriptive statistics, chi-squared association tests, prevalence ratios, and 95%
      confidence intervals were utilized. Adjusted analysis was carried out by Poisson
      regression. RESULTS: Among the interviewees, around 7% reported pulmonary
      disease. There was no association between pulmonary disease and influenza
      vaccination. Adjusted analysis identified the following factors that were
      independently associated with reported disease: smoking (PR: 2.03; 95% CI: 1.39
      2.97); medication use (PR: 2.05; 95% CI: 1.11-3.79); health status self-assessed
      as poor or very poor (PR: 1.89; 95% CI: 1.20-2.96); and depression, anxiety, or
      emotional problems (PR: 1.86; 95% CI: 1.11-3.10). CONCLUSIONS: The findings from
      the present study reinforce the importance of respiratory diseases among the
      elderly, particularly in more vulnerable groups. Preventive measures and specific
      care for such groups are therefore justified.

PMID- 16810367
TI  - [Individual factors associated with medical consultation by adults].
AB  - OBJECTIVE: To identify individual characteristics associated with a higher
      likelihood of consulting a physician and excess physician appointments. METHODS:
      We carried out a population-based study including 3,100 adults (> 20 years)
      living in the city of Pelotas, Southern Brazil between October and December 2003,
      using a multi-stage cluster sampling strategy. Subjects were interviewed to
      obtain socioeconomic, demographic, and health-related data, as well as
      information on the number of medical appointments in the past three months.
      Overusage was defined as > 4 appointments. Multivariate analysis was carried out
      using Poisson regression based on a conceptual model, and results are presented
      as prevalence ratios and their respective 95% confidence intervals. RESULTS: The
      prevalence of medical appointments was 55.1%. Higher likelihood of consulting a
      physician was associated with female sex, hospital admission in the past year,
      former smoking, diabetes, and arterial hypertension. We found an increasing trend
      in the number of appointments with increasing age (p < 0.001) and decreasing self
      perceived health status (p < 0.001). Prevalence of over utilization was 9%, and
      showed positive association with increased body mass index, (p = 0.01),
      increasing age (p = 0.006), and decreasing self-perceived health status (p <
      0.001). CONCLUSIONS: Presence and over utilization of physician appointments were
      associated with female sex, hypertension, and hospital admission in past year, as
      well as with increasing age and decreasing self-perceived health status.

PMID- 16810368
TI  - [Price differences between generic and innovator medicines in Brazil].
AB  - OBJECTIVE: To assess the magnitude of price difference between generic and
      innovator medicines and to evaluate the effect of the price competition between
      them. METHODS: From January 2000 to June 2004, 135 generic medicines and their
      respective innovator medicines were followed up for a period of up to four years.
      Prices were extracted from pharmaceutical market specific publications and
      recorded from the launching of generics and during their marketing period.
      RESULTS: The generic medicines were introduced on average at prices 40% lower
      than the innovator ones and this difference tended to increase over the years.
      The price difference between generic and innovator medicines increased in the
      subsequent four-year period after generic launching in 68%. CONCLUSIONS: The
      introduction of generic medicines in the Brazilian pharmaceutical market
      contributed for offering cheaper medicines. However, the competition between
      generic and innovator medicines did not promote markdown of the majority
      innovator medicines.

PMID- 16810369
TI  - Performance of rubella suspect case definition: implications for surveillance.
AB  - OBJECTIVE: To assess the performance of the rubella suspect case definition among
      patients with rash diseases seen at primary care units. METHODS: From January
      1994 to December 2002, patients with acute rash, with or without fever, were seen
      at two large primary health care units and at a public general hospital in the
      municipality of Niteroi, metropolitan area of Rio de Janeiro, Brazil. Data from
      clinical and serologic assessment were used to estimate the positive predictive
      values of the definition of rubella suspect case from the Brazilian Ministry of
      Health and other combination of signs/symptoms taking serologic status as the
      reference. Serum samples were tested for anti-rubella virus IgM using
      commercially available enzyme immunoassays. Positive predictive values and
      respective 95% confidence intervals were calculated. RESULTS: A total of 1,186
      patients with an illness characterized by variable combinations of rash with
      fever, arthropathy and lymphadenopathy were studied. Patients with rash,
      regardless of other signs and symptoms, had 8.8% likelihood of being IgM-positive
      for rubella. The Brazilian suspect case definition (fever and lymphadenopathy in
      addition to rash) had low predictive value (13.5%). This case definition would
      correctly identify 42.3% of the IgM-positive cases, and misclassify 26.1% of the
      IgM-negative cases. CONCLUSIONS: These results support the recommendation to
      investigate and collect clinical specimens for laboratory diagnosis of all cases
      of rash, for surveillance purposes. Although this strategy may increase costs,
      the benefits of interrupting the circulation of rubella virus and preventing the
      occurrence of congenital rubella syndrome should pay off.

PMID- 16810370
TI  - Obesity and gestational weight gain: cesarean delivery and labor complications.
AB  - OBJECTIVE: To assess the association between pre-gestational obesity and weight
      gain with cesarean delivery and labor complications. METHODS: A total of 4,486
      women 20-28 weeks pregnant attending general prenatal care clinics of the
      national health system in Brazil from 1991 to 1995 were enrolled and followed up
      through birth. Body mass index categories based on prepregnancy weight and total
      weight gain were calculated. Associations between body mass index categories and
      labor complications were adjusted through logistic regression analysis. RESULTS:
      Obesity was present in 308 (6.9%) patients. Cesarean delivery was performed in
      164 (53.2%) obese, 407 (43.1%) pre-obese, 1,045 (35.1%) normal weight and 64
      (24.5%) underweight women. The relative risk for cesarean delivery in obese women
      was 1.8 (95% CI: 1.5-2.0) compared to normal weight women. Greater weight gain
      was particularly associated with cesarean among the obese (RR 4th vs 2nd weight
      gain quartile 2.2; 95% CI: 1.4-3.2). Increased weight at the beginning of
      pregnancy was associated with a significantly higher adjusted risk of meconium
      with vaginal delivery and perinatal death and infection in women submitted to
      cesarean section. Similarly, greater weight gain during pregnancy increased the
      risk for meconium and hemorrhage in women submitted to vaginal delivery and for
      prematurity with cesarean. CONCLUSIONS: Pre-gestational obesity and greater
      weight gain independently increase the risk of cesarean delivery, as well as of
      several adverse outcomes with vaginal delivery. These findings provide further
      evidence of the negative effects of prepregnancy obesity and greater gestational
      weight gain on pregnancy outcomes.

PMID- 16810371
TI  - [Consequences of sociodemographic inequalities on birth weight].
AB  - OBJECTIVE: To analyze sociodemographic inequalities in prenatal and childbirth
      care and their consequences on birth weight. METHODS: The study was based on a
      sample of 10,072 postpartum women treated at public (those outsourced by the
      National Health System) and private maternity hospitals in Rio de Janeiro,
      Brazil, from 1999 to 2001. To test the association between birth weight and
      maternal sociodemographic and biological characteristics and prenatal care
      (modified Kotelchuck index), postpartum women were stratified by level of
      schooling and two multiple linear regressions were performed. The bootstrap
      technique was used in addition to accurate confidence intervals for the estimated
      effects. RESULTS: For nearly all of the variables analyzed in the bivariate
      analysis, birth weight was lower among children of mothers with low schooling. In
      the multivariate analysis, among women with low schooling, there was a direct
      association between birth weight and the modified Kotelchuck index and
      gestational age. The variables black skin color, smoking, and history of
      premature birth were negatively associated with birth weight, while maternal age
      and parity showed distinct behaviors from the central range of data at the
      extremes. In the group with high schooling, only parity, gestational age, and
      modified Kotelchuck index were significant and directly associated with birth
      weight. The protective effect of prenatal care was observed, as well as the
      negative effect of smoking, regardless of the mother's level of schooling.
      CONCLUSIONS: The variables associated with neonates' birth weight of mothers with
      high schooling in Rio de Janeiro were biological, in contrast to the social
      determinants in the group with low schooling.

PMID- 16810372
TI  - [AIDS and pregnancy: meanings of risk and challenges for care].
AB  - OBJECTIVE: To understand how the risk of vertical HIV transmission is perceived
      and interpreted by people living with HIV/AIDS, when making decisions regarding
      reproductive health. METHODS: This was a qualitative study carried out at three
      municipal health clinics specializing in STD/AIDS, in the city of Sao Paulo. Semi
      structured thematic interviews were conducted with eight patients (male and
      female), from July to December 2001. The interviewees were key informants and
      either they or their partners were seropositive. All of them were aged 18 or over
      and had been living with their partners for at least one year. RESULTS: Among the
      motivations for having children, those related to the partner's expectations were
      highlighted, especially as a form of "recompense" for their actions. The risk of
      vertical transmission was used by health professionals both for discouraging
      pregnancy and for giving guidance on transmission prophylaxis. However,
      reproductive issues were not voiced at the health clinics, either by the patients
      or by the healthcare providers. CONCLUSIONS: Attention should be directed not
      only towards controlling the infection, but also most importantly towards the
      wellbeing of people living with HIV/AIDS. There is a need to clarify the
      different points of view of users and professionals in order to achieve the most
      effective and appropriate solution for each specific caregiving situation.

PMID- 16810373
TI  - [Risk factors for HIV infection among patients infected with hepatitis C virus].
AB  - OBJECTIVE: Human immunodeficiency virus and hepatitis C virus share the same
      routes of transmission. Currently, there is a high frequency of co-infection
      worldwide, especially among users of injectable drugs and in subjects with
      history of blood transfusions. The aim of the present study was to evaluate risk
      factors associated to human immunodeficiency virus infection in patients infected
      with hepatitis C virus. METHODS: We carried out an epidemiological case-control
      study, including 118 patients (cases) infected by both viruses and 233 patients
      (controls) infected only by the hepatitis C virus. Between January 1999 and
      November 2001, patients responded to a questionnaire assessing sociodemographic
      and professional characteristics, and major risk factors for virus infection.
      After description and initial comparison, variables were evaluated by univariate
      analysis and then by multivariate logistic regression for variables selected
      through the maximum likelihood test. RESULTS: Co-infection was associated with
      female sex (OR = 2.89; 95% CI: 1.16-7.08), being divorced/widow (OR = 3.91; 95%
      CI: 1.34-11.35), past or current use of illegal drugs (OR = 3.96; 95% CI: 1.55
      10.13) and to the habit of sharing pipes or needles (OR = 10.28; 95% CI: 4.00
      6.42). CONCLUSIONS: Among patients infected with hepatitis C virus, female sex is
      a risk factor for HIV infection after adjustment for the habit of sharing pipes
      and needles. Being divorced/widow, use of illegal drugs, and the habit of sharing
      pipes and syringes were associated to co-infection.

PMID- 16810374
TI  - Body dissatisfaction in Brazilian schoolchildren: prevalence and associated
      factors.
AB  - OBJECTIVE: To examine the prevalence of body dissatisfaction and associated
      factors in 8- to 11-year-old schoolchildren. METHODS: A cross-sectional study
      including children aged 8- to 11-years enrolled in public and private schools in
      Porto Alegre, Southern Brazil, was carried out from August to December, 2001. A
      total of 901 subjects were selected through cluster sampling. Participants
      answered a questionnaire aimed at measuring body dissatisfaction and self-esteem
      and questions about family and social pressures on weight change. Height and
      weight were measured. The relationship between body dissatisfaction and the
      variables studied was measured by logistic regression. RESULTS: The prevalence of
      body dissatisfaction was 82%. Fifty-five percent of the girls wanted a thinner
      body size, and 28% desired a larger one; the estimates for the boys were 43% and
      38%, respectively. Children with the lowest self-esteem (OR = 1.80; 95% CI: 1.13
      2.89) and who thought their parents (OR = 6.10; 95% CI: 2.95-12.60) and friends
      (OR = 1.81; 95% CI: 1.02-3.20) expected them to be thinner showed a higher chance
      of presenting body dissatisfaction. CONCLUSIONS: Body dissatisfaction was highly
      prevalent among the evaluated schoolchildren, especially in those with lower self
      esteem and who thought their parents and friends expected them to be thinner.

PMID- 16810376
TI  - [Parity of Ochlerotatus scapularis in laboratory and field conditions].
AB  - OBJECTIVE: To identify the parity status of Ochlerotatus scapularis females in
      laboratory and field conditions. METHODS: Field collections were carried out
      fortnightly using a hand-held aspirator in Vale do Ribeira, Southeastern Brazil,
      from April 2003 to March 2004. In laboratory, 100 Ochlerotatus scapularis F1
      females were obtained and followed up individually, reporting the number of blood
      meals, the length of gonotrophic cycle, survival and number of eggs laid. The
      parity status and ovarian development were observed through ovarian dissection of
      90 field females for each collection and all females reared in laboratory.
      RESULTS: The parity status diagnoses of the 100 females reared in laboratory and
      dissected agreed with 55% of the oviposition data, and it was underestimated in
      37% and overestimated in 2%. Also in the laboratory, 106 gonotrophic cycles were
      completed, around 55% of females needed more than one blood meal before laying
      eggs. In laboratory conditions the species survival was 26 days. A total of 1,180
      field females of Ochlerotatus scapularis were dissected: 418 (35.4%) nulliparous,
      655 (55.5%) uniparous, 46 (3.9%) biparous and 61 (5.2%) could not be evaluated.
      Ninety field females were found in Christophers and Mer's phase III-V.
      CONCLUSIONS: The gonotrophic discordance hypothesis could be confirmed based on
      field and laboratory observations of Ochlerotarus scapularis females.

PMID- 16810375
TI  - [Relationship between body mass index and self-perception among university
      students].
AB  - OBJECTIVE: To assess the relationship between body mass index and self-perception
      of body image. METHODS: A study was carried out in a sample comprising 106 female
      and male university students aged 18 years or more in Ribeirao Preto,
      Southeastern Brazil, in 2003. The Contour Drawing Rating Scale and Visual
      Analogue Scale were used to evaluate body image perception; the former was
      applied using two different psychometric methods. A body image questionnaire was
      used to assess the subjective component of body image. Subjects were classified
      according to body mass index. Statistical analyses were performed through
      variance analysis and Newman-Keuls post-hoc test. RESULTS: Most normal weight or
      overweight women (87%) overestimated their body size while obese women and all
      men (73%), regardless of their BMI, underestimated their body size. The
      differences of body image perception between men and women were statistically
      significant as well as the overall dissatisfaction with their perceived body
      size, revealed by a desired lower body mass index. Overweight women were more
      concerned and uncomfortable with their own body. CONCLUSIONS: Both men and women
      had a distorted self-perception of body image, underestimating or overestimating
      it. The study results suggest dissatisfaction of subjects with their body image
      as they desire to have leaner bodies.

PMID- 16810377
TI  - [Advances in the Brazilian norm for commercialization of infant foods].
AB  - OBJECTIVE: To assess the advances in the Brazilian norm for commercialization of
      infant foods from 1988 to 2002, comparing the different texts with each other and
      with the International Code of Marketing of Breast-Milk Substitutes. METHODS:
      This was a descriptive study based on data collected from documents, reports,
      ordinances and resolutions from the Brazilian Ministry of Health. The versions
      utilized in the comparison were from 1992 and 2002. RESULTS: Comparative analysis
      made it possible to identify important advances in the legislation. In 1992,
      liquid and powdered milk were included in the scope, along with teats and dummies
      (pacifiers), and also warning phrases in advertising and on product labeling. In
      2002, regulations for products were published by the National Agency for Sanitary
      Surveillance, thereby strengthening supervisory actions and including regulations
      for baby foods, nutrient formulae for high-risk newborns, and nipple protectors.
      The phrases used in commercial advertising and on product labeling, including
      dummies, teats and bottles, became Ministry of Health warnings. The labeling was
      defined according to product types, on the basis of more restrictive rules.
      CONCLUSIONS: Significant modifications in the control over the marketing of
      products aimed at mothers during the lactation period. However, there are still
      some legislative questions that would make it possible to improve the Brazilian
      norm, in order to protect breastfeeding. There is also a need for the government
      to implement systematic monitoring routines to supervise this legislation.

PMID- 16810378
TI  - [Regulations, conflicts and ethics of medical research in developing countries].
AB  - The patient is the subject who may meet the needs and interests of medical
      investigators for their research. This intrinsic conflict becomes more evident
      and shows particularities in the context of research projects involving clinical
      trials in developing countries. Target populations in these countries have
      inadequate access to health services, little understanding of risks involved in a
      study and also less capacity to claim judicially in the event of damage. In
      general, the discussions on ethics in research in industrialized countries are
      characterized by a biomedical approach of disease, and a neoliberal vision of
      economy and trade. In fact, most biomedical research has been directed to benefit
      already privileged communities. Therefore, it is necessary to minimize the risk
      of exploitation of developing countries populations. The present study provides
      an outlook of ethical protection for human research in developing countries.

PMID- 16810379
TI  - [Socioanthropological notes on community and health].
AB  - The notion of community utilized by planners and healthcare providers is doubly
      deceptive. On the one hand, it presupposes apparent equality and absence of
      conflicts between people in the same population group. On the other hand, it
      supposes a certain possibility of intervention by healthcare services in relation
      to behavioral patterns that are considered undesirable, from the point of view of
      disease control or health promotion. Used this way, this concept ends up
      concealing the "social nature" of the target population: poor people and the
      setbacks that their condition of poverty causes. To bring to light the problem of
      the euphemism implicit in this notion of community, the objective of the present
      article was to present Simmel's radically relational approach for characterizing
      the subordination of these population groups to healthcare policies and programs.
      For this purpose, the starting point was the appropriation of the sociological
      notion of community by the healthcare services, from Tonnies' classic formulation
      and its influence on the authors of the Chicago school.

PMID- 16810380
TI  - [Current epidemiological status of visceral leishmaniasis in Northeastern
      Brazil].
AB  - The objective was to describe the current epidemiological status of visceral
      leishmaniasis in the State of Pernambuco, Northeastern Brazil. For that, a search
      for scientific production on epidemiology of visceral leishmaniasis in Pernambuco
      was carried out in electronic databases MEDLINE, SciELO and LILACS. Additionally,
      relevant papers that have not been retrieved from the searches were analyzed. The
      18 studies selected for this review indicate that: visceral leishmaniasis is
      widely spread in Pernambuco; human cases are often associated to anthropic
      pressure on the environment; and children have been more frequently affected by
      the disease. These results showed the need for further studies on risk factors
      for visceral leishmaniasis in humans, the role of Leishmania chagasi hosts in the
      zoonotic transmission cycle, and the vector behavior in different geographical
      regions.

PMID- 16810381
TI  - [Prevalence of Diabetes Mellitus in Southern Brazil: a population-based study].
AB  - OBJECTIVE: To compare the prevalence of Diabetes Mellitus among the adult
      population of an urban area, according to self-reported diabetes and fasting
      glucose test results. METHODS: We carried out a population-based cross-sectional
      study of 1,968 subjects aged 20-69 years, living in the urban area of the city of
      Pelotas, Southern Brazil, in the year 2000. Sample size was calculated at 1,800
      subjects. We visited the households of 40 randomly selected census sectors. We
      administered a standardized questionnaire to all subjects, which included
      questions on the presence of "blood sugar" and on medical confirmation in case of
      positive responses. A subsample of 367 participants was selected to donate blood
      samples for laboratory tests, including fasting blood glucose. We adopted as
      cutoff points for the detection of diabetes levels of 126 mg/dl and 140 mg/dl.
      Results are shown as frequencies and their respective 95% confidence intervals.
      RESULTS: Of the subjects interviewed, 110 (5.6%; 95% CI: 4.6-6.6) referred the
      presence of Diabetes Mellitus diagnosed by a physician. In the subsample of 367
      subjects who underwent blood testing, the prevalence of self-referred, physician
      confirmed diabetes mellitus was 7.1% (95% CI: 4.5-9.7). CONCLUSIONS: The
      prevalence estimates found in the present study are compatible with those
      obtained in other national surveys. Population-based studies are rare Brazil, and
      may contribute to the planning of health care policies.

PMID- 16810382
TI  - [Interpretation of the tuberculin test].

PMID- 16810383
TI  - [From political to institutional action: research priorities in the Ministry of
      Health].

PMID- 16810384
TI  - [Impact of accidents and violence on health costs].

PMID- 16810385
TI  - [Tuberculosis among incarcerated population].

PMID- 16810388
TI  - Is there place for placebo controlled trials in the treatment of affective
      disorders?

PMID- 16810389
TI  - Evaluating endophenotypes for psychiatric disorders.

PMID- 16810390
TI  - Bipolar depression: the importance of being on remission.
AB  - OBJECTIVE: The aim of the present study is to compare quality of life among
      currently depressed, subsyndromal and remitted patients with bipolar disorder
      (BD) and to assess whether the level of depression correlates with the scores of
      quality of life in BD patients. METHOD: Sixty bipolar outpatients diagnosed using
      the Structured Clinical Interview for DSM-IV who met criteria for diagnosis of BD
      type I, II or not otherwise specified (BD-NOS), and who were not currently on a
      manic or mixed episode were included. The main variables of interest were quality
      of life (QOL) assessed using the 26-item World Health Organization QOL instrument
      (WHOQOL-BREF) and depression assessed using the 17-item Hamilton Depression
      Rating Scale (HDRS). RESULTS: A linear trend test showed a dose response
      association between patients' current mood state and all domains of quality of
      life. Higher quality of life scores were found among remitted patients, followed
      by subsyndromal patients; depressed patients presented lower scores of quality of
      life, except for the social domain. The four domains of the WHOQOL scale
      correlated negatively with the HDRS. CONCLUSIONS: Our findings suggest that
      bipolar depression and residual symptoms of depression are negatively correlated
      with QOL in BD patients.

PMID- 16810392
TI  - Patients' relatives delayed help seeking after a first psychotic episode.
AB  - OBJECTIVE: Recent studies show that proper treatment after the first psychotic
      episode may be delayed for a long time. Some patients remain without care even
      while exhibiting serious symptoms. The objective of the study was to understand
      the reasons why patients' relatives waited at least 6 months to look for
      psychiatric counseling and treatment. METHOD: Qualitative analyses of semi
      structured interviews with 15 relatives (of patients with first psychotic
      episode) who have waited more than six months before seeking psychiatric
      treatment were applied. The interviews were recorded; transcribed and relevant
      portions were codified and grouped, forming terms, concepts or categories.
      RESULTS: These family members referred to individuals with mental problems in
      other families in a stereotyped fashion, citing negative aspects such as violence
      and criminality. They used softer terms when referring to their family members.
      Not knowing that their sick relative to be a case of mental illness, relatives
      classified certain observed behaviors as coming principally from spiritual
      problems and drug use. The initial delay in seeking medical help for the sick
      person was influenced by: 1) stereotyped misconceptions used by relatives to
      understand mental problems; 2) explanatory models elaborated to try to understand
      the sick person's behavior; 3) fear of psychiatric treatment; and 4) negative
      experiences with psychiatric services. CONCLUSIONS: Cultural aspects are present
      at all levels of this elaboration process. Their proper understanding by
      physicians can considerably diminish relatives' pain and suffering.

PMID- 16810391
TI  - Diagnosis and pharmacological treatment of depressive disorders in a general
      hospital.
AB  - OBJECTIVE: To determine the point prevalence of depressive disorders in medical
      inpatients, to identify related sociodemographic and medical factors and to
      evaluate the psychotropic treatment given. METHOD: A cross-sectional study
      identifying the prevalence of depressive disorders and related factors combined
      with a prospective longitudinal study evaluating the psychopharmacological
      treatment were conducted. Medical inpatients, aged 18 years or older, presenting
      suitability to be interviewed and giving written informed consent were selected.
      The sample was composed of 125 subjects. The following instruments were used: a
      sociodemographic questionnaire; the Mini International Neuropsychiatric
      Interview; and the Beck Depression Inventory. Data related to medical, personal
      and family histories of psychiatric disorders and psychotropic use were collected
      by interview and from patient charts. The study took place at the Hospital Santa
      Isabel, in Blumenau, located in the state of Santa Catarina, Brazil, from January
      to July of 2002. RESULTS: The prevalence of depressive disorders was 26%. The
      factors that correlated with depressive disorders were being female, having an
      income lower than 3 times the minimum wage, having a personal history of
      depressive disorders, using psychotropic drugs, scoring higher than 13 on the
      Beck Depression Inventory and having been referred for a psychiatric consultation
      (p < 0.05). Only 43.8% of the individuals with depressive disorders received
      antidepressants. Most of the depressed patients were being treated with
      benzodiazepines (62.5%). The most frequently prescribed drugs were diazepam and
      fluoxetine. CONCLUSIONS: Approximately one-quarter of the medical inpatients had
      depressive disorders. However, antidepressants were prescribed for less than half
      of them. Women with a history of depression, using benzodiazepines and having a
      low income presented significantly higher rates of depressive disorders.
      Physicians should suspect depression in patients presenting such characteristics.

PMID- 16810393
TI  - Mental disorders prevalence among female caregivers of children in a cohort study
      in Salvador, Brazil.
AB  - OBJECTIVE: The caregiver-child relationship is important for child development.
      The prevalence of mental disorders was assessed in a female caregiver group and
      associated with socioenvironmental factors. METHOD: A cross sectional study was
      conducted in 326 caregivers whose children have been participating in a cohort
      study on mental development since 1999. RESULTS: The overall prevalence of mental
      disorders assessed according to the CIDI version 2.1 was 47.5% (95% CI 0.42
      0.53). They were predominantly anxiety disorders (32.8%; 95%CI 0.27-0.38),
      followed by mood disorders (26.1%; 95%CI 0.21-0.31) and psychoactive substance
      abuse (10.1%; 95%CI 0.07-0.13). Anxiety and mood disorders were less likely in
      younger caregivers and substance abuse disorder was less likely among those
      better educated. DISCUSSION: The overall prevalence was similar to previous
      estimates, although 32.8% of anxiety disorders exceeded previous findings, which
      is unsurprising in a female sample. CONCLUSIONS: Younger caregivers with higher
      schooling were more likely to have better mental health, which favors child
      development.

PMID- 16810394
TI  - Depressive symptoms and cognitive performance of the elderly: relationship
      between institutionalization and activity programs.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of depressive
      symptoms and to evaluate cognitive performance of institutionalized versus non
      institutionalized elderly subjects and to compare the effect of
      institutionalization and participation in the institution's activity programs on
      their cognitive performance. METHOD: A group of 120 elderly subjects with a mean
      age of 71 years and average schooling of 4.2 years was evaluated. The
      participants were divided into 3 groups: non-institutionalized (n = 37);
      institutionalized with activities (n = 37); institutionalized without activities
      (n = 46). The groups were matched for age, gender and educational level. The
      following assessment instruments were used: the Geriatric Depression Scale, the
      Mini-Mental State Examination, the Verbal Fluency Test and the computerized
      versions of the Hooper Visual Organization Test and the Boston Naming Test. The
      data were analyzed using one-way ANOVA and the Pearson's correlation test.
      RESULTS: The two groups of institutionalized elderly showed higher frequency of
      depressive symptoms when compared to non-institutionalized subjects and worse
      performance on the Verbal Fluency Test. The institutionalized group without
      activities had lower scores on Mental State Examination, Boston Naming Test and
      Hooper Visual Organization Test when compared to the other two groups (p < 0.05).
      CONCLUSIONS: Institutionalization of the elderly seems to be related to worse
      cognitive performance. Activity programs during institutionalization may be
      effective in minimizing cognitive functional loss.

PMID- 16810395
TI  - Teenage pregnancy: use of drugs in the third trimester and prevalence of
      psychiatric disorders.
AB  - OBJECTIVE: To determine the prevalence of psychiatric disorders during pregnancy,
      the prevalence of cocaine and marijuana use during the third trimester of
      gestation and the socio-demographic characteristics of a population of low-income
      teenagers. METHOD: One thousand pregnant teenagers were evaluated using the
      Composite International Diagnostic Interview, and a socio-demographic and socio
      economic questionnaire at the obstetric center of a public hospital in Sao Paulo,
      Brazil. Hair sample was collected for analysis. RESULTS: Of the 1000 pregnant
      teenagers interviewed, 53.6% were poor, 90.4% were unemployed, 92.5% were
      financially dependent and 60.2% dropped out of school. Those using drugs during
      the third trimester of pregnancy were equal to 6% (marijuana: 4%, cocaine: 1.7%,
      both: 0.3%). Those having at least one psychiatric disorder equaled 27.6%. The
      most frequent diagnoses were depression (12.9%), posttraumatic stress disorder
      (10.0%) and anxiety disorders (5.6%). DISCUSSION: Unstructured families, dropping
      out of school, unemployment and a low level of professional training are all
      contributing factors to the maintenance of an unfavorable socio-economic
      environment in which there is a high prevalence of cocaine and marijuana use
      during the third trimester of pregnancy and an abnormally high incidence of
      psychiatric disorders.

PMID- 16810396
TI  - Excessive daytime sleepiness in patients with depressive disorder.
AB  - OBJECTIVE: To evaluate excessive daytime sleepiness in patients with depressive
      disorder and to examine its association with the severity of depression and
      suicidal ideation. METHOD: Seventy patients were interviewed and assessed by the
      Epworth Sleepiness Scale (ESS), the Beck Depression Inventory (BDI) and the Beck
      Scale for Suicidal Ideation (SSI). Descriptive analysis, Pearson correlations and
      Student's t-test were used for data analyses. RESULTS: Most of the patients
      (57.1%) obtained high scores on the ESS. Correlation was positive and strongly
      significant between ESS scores and BDI scores, as well as between ESS scores and
      SSI scores. Patients with high ESS scores obtained higher mean BDI and SSI scores
      in comparison to patients with lower ESS scores. Significant differences (p <
      0.05) were encountered when the patients with higher (> or = 10) and lower (< 10)
      ESS scores were compared in terms of total ESS, BDI and SSI scores. CONCLUSIONS:
      Excessive daytime sleepiness was frequent among patients and significantly
      associated with higher levels of depression and particularly with suicidal
      ideation. Thus, a careful investigation of daytime sleepiness in depressed
      patients is required during clinical evaluation.

PMID- 16810397
TI  - The effect of 5-HT(2a/2c) receptor agonist microinjected into central amygdaloid
      nucleus and median preoptic area on maternal aggressive behavior in rats.
AB  - OBJECTIVE: Much evidence supports the hypothesis that 5-hydroxytryptamine (5-HT)
      activation is related to the inhibition of aggression. We examined potentially
      pro- and anti-aggressive effects of the 5-HT(2A/2C) receptor agonist on specific
      brain sites. METHOD: Female Wistar rats on the 7th day postpartum were
      microinjected with the selective 5-HT(2A/2C) receptor agonist, alpha-methyl-5
      hydroxytryptamine maleate (0.2 to 1.0 microg/0.2 microl) into the central
      amygdaloid nucleus and median preoptic nucleus. For each brain area studied, the
      frequency of the behaviors: locomotion, social investigation, lateral threat,
      attacks (frontal and lateral), and biting the intruder were compared among the
      various treatments by an Analysis of Variance, followed when appropriate, by
      Tukey's test. RESULTS: Microinjection of the selective 5-HT(2A/2C) receptor
      agonist, a-methyl-5-hydroxytryptamine maleate into central amygdaloid nucleus
      increased maternal aggression in the absence of concurrent changes in non
      aggressive behavior. By contrast, microinjection of the selective 5-HT(2A/2C)
      receptor agonist at several dilutions into the median preoptic nucleus did not
      alter aggressive behavior. CONCLUSIONS: The current and earlier data with pro-
      and anti-aggressive effects of the 5-HT(2a/2c) receptor agonist, when
      microinjected into the median preoptic nucleus relative to the central amygdaloid
      nucleus, medial septum and periaqueductal grey area in female rats point to
      functionally separate serotonin receptor populations in the amygdaloid-septal
      hypothalamic and periaqueductal gray matter areas controlling aggressive
      behavior. It is possible that amygdaloid 5-HT(2a/2c) receptors may increase
      aggressive behavior in lactating females as a result of changes in fear.

PMID- 16810398
TI  - [Experimental models of schizophrenia--a review].
AB  - OBJECTIVE: Diagnostic and therapy of somatic diseases like diabetes and
      hypertension have improved notably with the use of experimental models. For
      schizophrenia the proposal of a model has made little impact and even scepticism.
      Nevertheless the most recent studies indicate that "Cognitive Sciences" applied
      to specific models may help us to find out mechanisms of the disease. This
      article reviews the models presently under investigation for schizophrenia.
      RESULTS AND DISCUSSION: The difficulty to model schizophrenia results from the
      subjectivity of its symptoms, the difficult to reproduce them in animals and the
      disease complexity. Research on such a complex phenotype can only proceed by
      separating its components (endophenotypes) from each other and by the respective
      manipulation of its experimental counterparts, made by specific interventions
      (e.g. pharmacological, surgical, genetic), in the search of a common mechanism
      leading to these endophenotypes. For integrating these findings with symptoms a
      global explanatory theory is required. So far, the disease seems to result from a
      diffuse neuronal disconnection as a consequence of minor brain abnormalities with
      a genetic and/or environmental cause. CONCLUSIONS: An integrative approach of the
      diversity of models presently used may improve our understanding of
      schizophrenia.

PMID- 16810399
TI  - [Guidelines of the Brazilian Association of Studies on Alcohol and Other Drugs
      (ABEAD) for diagnoses and treatment of psychiatric comorbidity with alcohol and
      other drugs dependence].
AB  - Recently, several studies have focused on comorbity psychiatric disorders with
      alcohol and other substance dependence. The Brazilian Association of Studies on
      Alcohol and Other Drugs proposed the Brazilian Guidelines project. This study
      review diagnostic and therapeutic criteria to the most prevalent psychiatric
      comorbidities. Randomized clinical trials, epidemiological, animal studies and
      other forms of research are reviewed. The main psychiatric comorbidities are
      studied based on guidelines adopted by other countries and the literature data
      resumed. Epidemiological aspects, diagnoses, integrated treatment and service
      organization, as well as specific psychotherapic and pharmacological treatment
      are discussed. The Brazilian Association of Studies on Alcohol and Other Drugs
      Guidelines reassures the importance of adequate diagnoses and treatment regarding
      alcoholic and drug dependent patients suffering of comorbid psychiatric
      disorders.

PMID- 16810400
TI  - Is the outcome of schizophrenia really better in developing countries?
AB  - That schizophrenia has a better prognosis in non-industrialized societies has
      become an axiom in international psychiatry; the evidence most often cited comes
      from three World Health Organization (WHO) cross-national studies. Although a
      host of socio-cultural factors have been considered as contributing to variation
      in the course of schizophrenia in different settings, we have little evidence
      from low-income countries that clearly demonstrates the beneficial influence of
      these variables. In this article, we suggest that the finding of better outcomes
      in developing countries needs re-examination for five reasons: methodological
      limitations of the World Health Organization studies; the lack of evidence on the
      specific socio-cultural factors which apparently contribute to the better
      outcomes; increasing anecdotal evidence describing the abuse of basic human
      rights of people with schizophrenia in developing countries; new evidence from
      cohorts in developing countries depicting a much gloomier picture than originally
      believed; and, rapid social and economic changes are undermining family care
      systems for people with schizophrenia in developing countries. We argue that the
      study of the long-term course of this mental disorder in developing countries is
      a major research question and believe it is time to thoroughly and systematically
      explore cross-cultural variation in the course and outcome of schizophrenia.

PMID- 16810401
TI  - History of cannabis as a medicine: a review.
AB  - Cannabis as a medicine was used before the Christian era in Asia, mainly in
      India. The introduction of cannabis in the Western medicine occurred in the midst
      of the 19th century, reaching the climax in the last decade of that century, with
      the availability and usage of cannabis extracts or tinctures. In the first
      decades of the 20th century, the Western medical use of cannabis significantly
      decreased largely due to difficulties to obtain consistent results from batches
      of plant material of different potencies. The identification of the chemical
      structure of cannabis components and the possibility of obtaining its pure
      constituents were related to a significant increase in scientific interest in
      such plant, since 1965. This interest was renewed in the 1990's with the
      description of cannabinoid receptors and the identification of an endogenous
      cannabinoid system in the brain. A new and more consistent cycle of the use of
      cannabis derivatives as medication begins, since treatment effectiveness and
      safety started to be scientifically proven.

PMID- 16810402
TI  - Association study between the 1287 A/G exonic polymorphism of the norepinephrine
      transporter (NET) gene and obsessive-compulsive disorder in a Brazilian sample.

PMID- 16810403
TI  - Treatment emergent affective switch with topiramate.

PMID- 16810404
TI  - [Cultural aspects importance in a case with psychomotor agitation].

PMID- 16810405
TI  - Tardive dystonia, a case report.

PMID- 16810406
TI  - Obsessive-compulsive symptoms in non-active rheumatic fever.

PMID- 16810407
TI  - [Reversible clozapine-induced agranulocytosis].

PMID- 16810408
TI  - Limbic encephalitis manifesting as a psychotic disorder.

PMID- 16810409
TI  - [Persistent neurotoxicity secondary to lithium use: case report].

PMID- 16810410
TI  - [Comment on "Quality of life in siblings of autistic patients--II"].

PMID- 16810413
TI  - [Cardiovascular comorbidities and obstructive sleep apnea].

PMID- 16810414
TI  - [Additional cardiovascular risk factors associated with excess weight in children
      and adolescents: the Belo Horizonte heart study].
AB  - OBJECTIVE: To examine the association of overweight and obesity with physical
      activity, blood pressure (BP) and serum lipid profiles. METHODS: Epidemiologic
      investigation of 1,450 students, between the ages of 6 and 18, in the city of
      Belo Horizonte, MG. DATA: weight, height, BP, skinfold thickness, waist
      circumference, physical activity, total cholesterol (TC), LDL-c, HDL-c, and
      dietary habits. RESULTS: The prevalence rates for overweight and obesity were
      8.4% and 3.1%, respectively. In relation to the students in the lower quartile
      (Q1) of the distribution of subscapular skinfold, the students in the upper
      quartile (Q4) presented a 3.7 times higher risk (odds ratio) of having elevated
      TC levels. Overweight and obese students had a 3.6 times higher risk of having
      elevated systolic blood pressure, and a 2.7 times higher risk of elevated
      diastolic blood pressure when compared to normal weight students. The less active
      students in the Q1 of distribution of MET presented a 3.8 times higher risk of
      having elevated TC levels compared to those who were more active (Q4).
      CONCLUSION: Students who were overweight, obese or in the upper quartiles for
      other adiposity variables, as well as students with low levels of physical
      activity or a sedentary lifestyle presented higher blood pressure levels and a
      lipid profile indicative of an increased risk of developing atherosclerosis.

PMID- 16810415
TI  - [Concentration of serum lipids and apolipoprotein B in newborns].
AB  - OBJECTIVE: To determine the concentrations of serum lipids and apolipoprotein B
      (apo-B) in a population of normal full-term and preterm newborns in a city in
      Southern Brazil, and assess the impact of gestational age and birth weight on
      these values. METHODS: Two hundred and twelve newborns of both genders were
      studied, 142 of whom were full-term (>37 weeks of gestation) and 70 preterm (<37
      weeks of gestation). According to their birth weights, the full-term and preterm
      newborns were classified as small for gestational age or appropriate for
      gestational age. Umbilical cord blood was collected for biochemical analysis.
      RESULTS: The total cholesterol, LDL-C, HDL-C and apo-B values were higher in
      preterm newborns (79+/-34, 26+/-6, 45+/-15 and 36+/-14 mg/dL, respectively) than
      in full-term newborns (58+/-19, 20+/-10, 31+/-14 and 28+/-7 mg/dL, respectively;
      p < 0.0001). Inversely, triglyceride values were lower in preterm newborns (36+/
      14 mg/dL) than in full-term newborns (43+/-25 mg/dL; p < 0.0018). Gender and size
      at birth did not have any impact on the values of total cholesterol and
      fractions, triglycerides, and apo-B. CONCLUSION: Plasma concentrations of lipids
      and apo-B in the population of newborns studied are similar to those in newborns
      from other countries and continents reported in medical literature and, as
      expected, are markedly lower than the values mentioned in literature for infants
      over two years of age. Fetal maturity has an impact on the concentration of
      lipids in newborns, but birth weight does not have any effect on these
      parameters.

PMID- 16810416
TI  - [Influence of preload reduction on Tei index and other Doppler echocardiographic
      parameters of left ventricular function].
AB  - OBJECTIVE: To assess the influence of preload reduction by hemodialysis on
      Doppler Tei Index of myocardial performance and other parameters of cardiac
      function. METHODS: The Tei index and left ventricular (LV) systolic and diastolic
      function parameters were estimated, before and after a single hemodialysis
      session. Only subjects who were in sinus rhythm, without history of coronary
      artery disease, and no evidence of cardiac valve disease and pericardial effusion
      were included in the study. RESULTS: Fifteen patients (8 men, mean age 53 +/- 14
      years) completed the study. After an ultrafiltration of 2.2 +/- 1.1 liters, peak
      mitral E velocity decreased (p < 0.05) and A velocity remained unchanged (p =
      ns), resulting in reduction of E/A ratio (p < 0.01). The Tei index increased
      (from 0.57 +/- 0.07 to 0.65 +/- 0.09, p < 0.01) because of significant
      prolongations in isovolumetric relaxation time (from 101 +/- 14 to 113 +/- 17 ms,
      p < 0.01) and ejection time (from 271 +/- 22 to 252 +/- 22, p < 0.05). The
      isovolumetric contraction time did not vary (p = ns). There was no change in
      diastolic tissue Doppler parameters, while systolic velocities increased (p <
      0.05). CONCLUSION: The Tei index was affected by hemodialysis-induced preload
      alterations, as well as other mitral inflow Doppler-derived parameters. The
      diastolic parameters of mitral annulus Doppler tissue were independent of
      preload, while systolic velocities suggested improved systolic function.

PMID- 16810417
TI  - [Echocardiographic criteria for the definition of ventricular dysfunction
      severity in aortic banded rats].
AB  - OBJECTIVE: The purpose of this study was to identify echocardiographic parameters
      that allow distinguishing different levels of cardiac dysfunction in aortic
      banded rats. METHODS: Wistar male rats (90-100 g) were subjected to aortic
      banding (n=23) or a sham operation (n=12). The following echocardiographic
      parameters were evaluated and used to group rats into groups with similar
      characteristics using cluster analysis: absolute values and after normalization
      to body weight of left ventricular end-diastolic diameter (LVDD) and left atrial
      systolic diameter; left ventricular end-systolic diameter (LVSD); LV weight to
      body weight ratio (LVW/BW); three indexes of left ventricular shortening
      (endocardial fractional shortening, EFS; midwall FS, MFS; and posterior wall
      shortening velocity, (PWSV). RESULTS: The cluster analysis could group aortic
      banded rats into two groups: mild (n=13) and severe (n=9) stage of heart failure.
      There was no overlapping among the values of the 95% confidence interval of the
      following parameters between the two groups: LVDD, LVSD, EFS, MFS, LVW/BW, and
      PWSV. CONCLUSION: It is feasible to distinguish two groups of aortic banded rats
      according to the level of cardiac dysfunction using those echocardiographic
      parameters. This allows to perform longitudinal studies in homogeneous groups of
      rats with aortic banding and cardiac dysfunction.

PMID- 16810418
TI  - [Cardiovascular risk factors in adolescents: biological and behavioral
      indicators].
AB  - OBJECTIVE: To provide descriptive information and investigate to what extent
      behavioral risk factors for cardiovascular diseases are associated with
      biological risk factors in the young population. METHODS: The sample included 452
      adolescents (246 girls and 206 boys) between 15 and 18 years of age selected in a
      high school in the city of Londrina, Parana. Risk factors of a behavioral nature
      were analyzed as regards insufficient physical activity, excessive intake of fat
      and cholesterol and smoking. As biological risk factor indicators we used
      overweight, high arterial pressure levels, and adverse concentration of serum
      lipids and lipoproteins. RESULTS: Approximately 20% of the girls and 16% of the
      boys presented at least one biological risk factor for development of
      cardiovascular diseases. Overweight was significantly associated with excessive
      intake of fats, while elevated arterial pressure was related to sedentary
      lifestyle and smoking. Excessive intake of fat and cholesterol indicated
      increased risk of undesirable concentrations of serum lipids and lipoproteins.
      The risk associated with altered blood pressure and serum lipids and lipoprotein
      was increased two-fold in smokers when compared with nonsmokers. CONCLUSION: The
      results reinforce the need for interventions targeted at the adoption of a
      healthy lifestyle, including the regular practice of physical exercise,
      appropriate dietary patterns, and abstention from smoking as of an early age.

PMID- 16810419
TI  - [Predictive value of ventilatory and metabolic variables for risk of death in
      patients with cardiac failure].
AB  - OBJECTIVE: To analyze the predictive value of respiratory, metabolic, and
      hemodynamic variables obtained during the cardiopulmonary stress test for the
      risk of death in patients with heart failure. METHODS: Eighty-seven NYHA
      Functional Class II and III patients were analyzed, ages 51 +/- 0.5 years, 26 of
      them with Chagas' disease, 30 with coronary ischemia, and 31 with idiopathic
      etiology. The cardiopulmonary stress test consisted of a ramp-protocol with 5 to
      15 W/min workload increments performed on a bicycle-ergonometer until exhaustion.
      RESULTS: In this study, the multiple Cox regression analysis of age, height,
      weight, body surface, and gender showed that these parameters were not
      statistically significant control factors. Oxygen uptake, ventilatory equivalent
      of oxygen, ventilatory equivalent of carbon dioxide production, oxygen pulse, and
      end-tidal partial pressure of carbon dioxide at the anaerobic threshold,
      respiratory compensation point, and peak exercise proved to be important death
      predictors in heart failure patients. The relationship between the increase in
      carbon dioxide output as a function of the increase in minute ventilation, and
      the association between the oxygen uptake increase and the elevation of the
      workload from the beginning of exercise to the anaerobic threshold were
      statistically significant predictors of death in heart failure patients (p<0.05).
      CONCLUSION: The cardiopulmonary stress test makes it possible to evaluate
      ventilatory, metabolic, and hemodynamic variables that may be utilized as
      important markers of life prognosis in these patients.

PMID- 16810420
TI  - [Resistive exercise in the evaluation of endothelial dysfunction in heart
      failure].
AB  - OBJECTIVE: To evaluate the use of resistive exercise in the study of endothelial
      dysfunction in heart failure (HF) comparatively to reactive hyperemia (RH).
      METHODS: Eighteen patients with heart failure and 15 normal volunteers were
      submitted to intermittent handgrip exercise in a pneumatic bag, at an intensity
      that corresponds to 75% of the previously assessed maximum load. Patients
      underwent high-resolution vascular ultrasonography for brachial artery diameter
      and flow evaluation as well as cardiac output determination at rest, RH and after
      exercise. The systolic flow index in the brachial artery and cardiac index were
      calculated. RESULTS: Systolic flow index increase in the brachial artery was
      observed after RH and physical exercise, with the latter presenting the highest
      increase. There was an increase in the cardiac index after the study conditions
      in comparison to resting conditions. CONCLUSION: Resistive exercise, performed at
      the assessed load, increases blood flow more intensively than RH, constituting a
      physiological option for the evaluation of endothelial function in HF.

PMID- 16810421
TI  - [Venous endothelial dysfunction in Chagas' disease patients without heart
      failure].
AB  - OBJECTIVE: To analyze the venous endothelial function in Chagas' disease patients
      without heart failure. METHODS: The Chagas' disease Group (G1) was composed by 14
      women and 2 men aged 46 +/- 2.7 and the Control Group (G0) by 7 women and 1 man
      matched by age, weight and height. Dorsal Hand Vein Compliance Technique was used
      to evaluate the venous endothelial function. Crescent doses of phenylephrine were
      infused to get a 70% pre-constriction of the vein; after that, acetylcholine and
      sodium nitroprusside were respectively administrated to analyze the endothelium
      dependent and -independent venodilation. RESULTS: No significant systemic
      hemodynamic changes were observed in both groups during the experiment. The
      necessary phenylephrine dose to reach 70% pre-constriction of the vein was
      significantly higher in the G1 (1116 +/- 668.2 ng/ml) compared to G0 (103 +/- 28
      ng/ml) p = 0.05. The endothelium-dependent venous dilation was significantly
      lower in G1 (65.5 +/- 8%) compared to G0 (137 +/- 20%) p = 0.009. No difference
      was observed in the endothelium-independent venous dilatation between groups.
      CONCLUSION: Patients with Chagas' disease without heart failure presented venous
      endothelial dysfunction.

PMID- 16810423
TI  - The future of liver transplantation in Singapore.

PMID- 16810422
TI  - [Ischemic heart disease mortality in the State of Rio de Janeiro between 1999 and
      2003].

PMID- 16810425
TI  - Rudolph Virchow (1821-1902): "pope of pathology".

PMID- 16810426
TI  - Controversial endocrine interventions for the aged.
AB  - Specific endocrine changes occur with the ageing process. The last decade has
      witnessed significant progress in the basic and clinical science of ageing,
      thereby rejuvenating the interest in anti-ageing medicine, especially that of
      hormone replacement, by medical professionals and the lay public. However,
      endocrine manipulation as a therapeutic strategy for ageing is still evolving as
      continuing research attempts to answer the many questions of what it can achieve
      at the risk of incurring unknown long-term adverse effects. The current day
      doctor is confronted with a host of options, and will benefit from a synopsis of
      the latest evidence before making the most appropriate decision for aged patients
      seeking hormonal replacement therapy as a means to counter the effects of ageing.
      This review aims to give a rapid overview of the endocrine profile of geriatric
      population and the studies on the more controversial hormonal replacement
      therapies for the aged.

PMID- 16810427
TI  - Liver transplantation in Singapore 1990-2004.
AB  - INTRODUCTION: Liver transplantation is the accepted standard of care for patients
      with hepatocellular carcinoma, decompensated liver cirrhosis, and acute liver
      failure. Since the first liver transplant done in Singapore in 1990, results have
      been improving. We review the overall results of liver transplantation over the
      last 15 years. METHODS: All transplant cases from 1990 to 2004 were reviewed
      retrospectively. RESULTS: 100 liver transplants were performed over the last 15
      years; four in the first five years and 96 in the subsequent ten years. Overall
      one- and five-year survival rates were 80 percent and 78 percent, respectively.
      44 were paediatric transplants, of which biliary atresia was the commonest
      indication for paediatric transplant. 56 were adult transplants of which
      hepatocellular carcinoma and decompensated hepatitis B cirrhosis were the
      commonest indications for adult transplant. Infection remained the commonest
      cause of mortality. CONCLUSION: The number of transplants carried out per year
      was small due to the low cadaveric donation rate, but the survival of liver
      transplant patients was comparable to well-established liver transplant centres.

PMID- 16810428
TI  - Liver transplantation for hepatocellular carcinoma in Singapore.
AB  - INTRODUCTION: The prognosis of patients with hepatocellular carcinoma (HCC) is
      poor. Surgical resection offers the benefit of removal of the tumour but is
      associated with liver decompensation and tumour recurrence, even after successful
      surgery. Liver transplantation offers the benefits of complete tumour removal
      with prevention of both decompensation and recurrence post-operation. This paper
      aims to review results of liver transplantation for patients with HCC in
      Singapore. METHODS: All adult patients with HCC accepted on the waiting list for
      liver transplantation (based on the Milan criteria) from 1996 to 2004 in
      Singapore were reviewed. Patients' HCC were managed with either transarterial
      chemoembolisation or percutaneous radiofrequency ablation while they were on the
      waiting list. Post-transplant survival and factors associated with mortality were
      analysed by Cox regression analysis. RESULTS: 41 patients with HCC were accepted
      onto the waiting list over the nine-year period. 22 underwent transplantation and
      19 did not, with a one-year survival of 91 percent versus 24 percent,
      respectively. (p-value is less than 0.001). Mean waiting time for transplant was
      39 weeks. Post-transplant HCC recurrence was 2/22 (nine percent). Among all
      patients, mortality was significantly related to baseline white cell counts,
      prothrombin time, age, alpha-foetoprotein level, Child-Pugh score, and whether
      patients underwent transplant. CONCLUSION: Despite the relatively long waiting
      time of a mean of 39 weeks, post-transplant recurrence of HCC was relatively low
      at nine percent. Liver transplant is an effective treatment for patients with a
      HCC, with a reasonable long-term survival.

PMID- 16810429
TI  - Long-term results of liver transplant in patients with chronic viral hepatitis
      related liver disease in Singapore.
AB  - INTRODUCTION: Liver disease from chronic hepatitis B (CHB) and C (CHC)
      constitutes 57 percent of adult liver transplant in Singapore. Their long-term
      results post-transplant may be affected by recurrence of the viral illness. This
      study aims to evaluate the long-term results and survival in patients
      transplanted for CHB- and CHC-related liver disease. METHODS: Patients
      transplanted for CHB- and CHC-related disease from 1990 until March 2004, which
      included decompensated cirrhosis and hepatocellular carcinoma (HCC), were
      reviewed and analysed. RESULTS: 25 patients were transplanted for CHB-related
      liver disease, with mean follow-up of 153 +/- 25 weeks. Two- and four-year
      survival rates were 75 percent and 69 percent, respectively. Hepatitis B
      recurrence from YMDD mutants occurred in five patients, and four were treated
      successfully with adefovir dipivoxil, with resolution in transaminases and/or
      improvement in histology. One patient became non-compliant with follow-up and
      medications, and died 173 weeks post-transplant from reactivation of the wild
      type hepatitis B virus. Nine patients were transplanted for CHC-related liver
      disease, with mean follow-up of 188 +/- 40 weeks, and two- and four-year survival
      rates of 89 percent and 76 percent, respectively. Two patients developed
      hepatitis C recurrence and were treated with interferon and ribavarin. One
      responded with sustained response but the other remained viraemic and died of HCC
      recurrence two years post-transplant. CONCLUSION: Long-term results from CHB- and
      CHC-related liver diseases were satisfactory and comparable to major transplant
      centres in the USA and Europe. Recurrence of viral hepatitis post-transplant is
      controllable with current antiviral therapy.

PMID- 16810430
TI  - MELD may not be the better system for organ allocation in liver transplantation
      patients in Singapore.
AB  - INTRODUCTION: The Model for End-Stage Liver Disease (MELD) score is a good
      predictor of mortality on the liver transplant waiting list and is the current
      system of organ allocation in the USA. However, a higher MELD may be associated
      with poorer outcome post-liver transplantation. The aim of this study was to
      determine if MELD should be implemented as the system for organ allocation for
      liver transplantation in Singapore. METHODS: There were 46 adult patients who
      underwent primary liver transplantation at the National University Hospital,
      Singapore from January 1996 to December 2002. We applied the MELD score to
      patients who were transplanted and looked for a correlation with survival post
      transplant. Patients were followed-up until the most recent visit or death.
      Survival analysis was performed using Cox regression and Kaplan-Meier method.
      RESULTS: The mean age at transplant was 52.7 (SD 2.34) years. The majority of the
      patients transplanted had Hepatitis B (43 percent). The median MELD score at
      transplantation was 17 (7-42) and the median Child's score was 11 (6-15). There
      was a significant correlation between pre-transplant MELD and survival at six
      months (p-value is 0.037, 95 percent confidence interval [CI] is 1.004-1.13) but
      not at one year (p-value is 0.065, 95 percent CI is 0.99-1.12). There were no
      differences in the pre-transplant MELD (odds-ratio [OR] 1, 95 percent CI 0.9-1)
      as well as survival for patients with and without Hepatitis B (OR 0.72, 95
      percent CI 0.22-2.35). CONCLUSION: MELD allows livers to be allocated to the
      patients with the greatest medical urgency but its influence on post-transplant
      survival should be further clarified so that post-transplant survival is not
      compromised.

PMID- 16810431
TI  - Outcome of liver transplantation for children with liver disease.
AB  - INTRODUCTION: The advent of liver transplantation has revolutionised the outcome
      of children with both acute liver failure and chronic end-stage liver disease.
      The aim of this study was to review the outcome of all paediatric liver
      transplants performed since the National Liver Transplant Programme began in
      1990. METHODS: A retrospective review of all paediatric liver transplants from
      1990 to December 2004 was performed. RESULTS: 46 liver transplants were performed
      in 43 children, of whom 23 (53.3 percent) were female. Median age at transplant
      was 21 months (range 11 months to 14 years). The most common indication for liver
      transplant was biliary atresia (71.7 percent). Living-related transplants
      accounted for 63 percent (29). Re-transplant rate was 6.5 percent with allograft
      loss as a result of hepatic artery thrombosis (two) and hepatic vein thrombosis
      (one). Tacrolimus was the primary immunosuppressive agent used in 89 percent of
      patients, with a 19.6 percent incidence of acute allograft rejection within the
      first six months. There were nine deaths. They were related to portal vein
      thrombosis (three), chronic rejection (one), sepsis (two), post-transplant
      lymphoproliferative disease (two) and primary graft non-function (one). Overall
      actuarial one- and five-year survival rate was 85.7 percent and 81.8 percent,
      respectively. CONCLUSION: Liver transplantation is an established form of
      intervention for end-stage liver disease and a variety of liver-related metabolic
      disease. Our results are comparable to those of well-established liver transplant
      centres.

PMID- 16810432
TI  - Referral patterns and waiting times for liver transplantation in Singapore.
AB  - INTRODUCTION: Referral patterns, waiting times, waiting list, and mortality
      provide information on how effectively a transplant programme deals with referred
      patients. This paper aims to review these parameters in the Singapore National
      Liver Transplant Programme. METHODS: Data of all patients referred to the
      Singapore National Liver Transplant Programme since its inception were captured
      and outcomes were retrieved and described. RESULTS: 562 patients were referred
      for liver transplant evaluation from 1990-2004, consisting of 457 adults and 105
      children. The main indications for referral were hepatitis B liver disease and
      hepatocellular carcinoma in adults, and biliary atresia in children. Most
      patients were of United Network of Organ Sharing (UNOS) status 3 or 4 at the time
      of referral. 114 (20.28 percent) patients had transplants, consisting of 66
      adults (14.44 percent) and 48 (45.71 percent) children. 138 adults and ten
      children were rejected for transplant, mainly for the reason of being "too
      early". The median waiting time for adults who had transplants was 3.3 months
      while adults still on the waiting list had been waiting for 16.2 months. The
      overall waiting list mortality was 44.3 percent, being 52.5 percent in adults and
      23.2 percent in children. CONCLUSION: The overall transplantation rate is low and
      the waiting list mortality is high as a result of low availability of organs,
      particularly in adults. Paediatric liver transplant appears to have been better
      at dealing with referred patients but this is probably due to availability of
      living-related liver transplant. Improvement in these may result from the Human
      Organ Transplant Act.

PMID- 16810433
TI  - Long-term post-liver transplant complications of renal impairment and diabetes
      mellitus: data from Singapore.
AB  - INTRODUCTION: Patients who survive the initial post-liver transplantation period
      face the development of chronic diseases in the long run. We studied two
      important complications of liver transplantation, namely: renal impairment and
      diabetes mellitus. METHODS: We analysed adult patients followed-up for more than
      one year using data from our liver transplant clinical records. Long-term post
      transplant renal impairment (RI) was defined as glomerular filtration rate (GFR)
      less than 60 ml/min/1.73 square metres and long-term post-transplant diabetes
      mellitus (DM) was defined as fasting blood glucose more than 7.8 mmol/L, that
      existed at least one year after liver transplantation. Pre- and post-transplant
      factors that could be associated with these conditions were examined. RESULTS:
      Altogether, 35 patients were evaluated. Mean age at transplant was 50 years. Mean
      duration of follow-up was 58.4 months. There was 11.4 percent of pre-transplant
      RI and 17.0 percent of pre-transplant DM. Prevalence of post-transplant RI was
      43.5 percent at one year and 45.0 percent at four years. Long-term post
      transplant RI was associated with renal impairment at six months post-transplant
      (p-value is 0.033). Prevalence of severe post-transplant RI (GFR is less than 30
      ml/min/1.73 square metres) at four years was 5.7 percent. Prevalence of post
      transplant DM was 45.5 percent at two years but declined to 5.3 percent at four
      years. CONCLUSION: Post-transplant renal impairment appears to be a potential
      long-term problem while post-transplant diabetes mellitus appears to improve with
      time.

PMID- 16810434
TI  - Pleural effusions: role of commonly available investigations.
AB  - INTRODUCTION: Previous studies have reported high rates of undetermined causes of
      pleural effusions. We aimed to find out the proportion of pleural effusions in
      which the aetiology is uncertain despite commonly available investigations.
      METHODS: A prospective study was carried out at the University of Malaya Medical
      Centre from May 2001 to January 2002. All patients with pleural effusion admitted
      to the medical wards and non-medical wards during that period were included in
      the study. RESULTS: Of 111 patients with pleural effusion, malignancy was the
      commonest cause of pleural effusion (34.2 percent), followed by tuberculosis
      (22.5 percent) and parapneumonic effusions (18.9 percent). There were only two
      patients (1.8 percent) with undetermined cause despite extensive investigations.
      Carcinoma of the lung was the commonest cause of malignant effusions and
      bronchoscopic biopsy gave the highest yield of histological diagnosis (66
      percent), followed by pleural fluid cytology (59 percent) and pleural biopsy (50
      percent). The combination of these three procedures increased the diagnostic
      yield to 96 percent. In tuberculous pleural effusion, pleural fluid staining for
      acid-fast bacilli was negative in all cases but mycobacterial culture was
      positive in 24 percent of cases while pleural biopsy gave a better yield of 68.8
      percent. Examination of sputum and bronchoalveolar lavage specimens confirmed the
      diagnosis of tuberculosis in 40 percent of cases. A combination of these
      investigations yielded the diagnosis in 92 percent of patients with tuberculous
      effusion. CONCLUSION: Malignancy is the commonest cause of pleural effusion,
      followed by tuberculosis and pneumonia, in patients treated in a teaching
      hospital in Malaysia. The number of undetermined causes could be minimised with a
      combination of readily-available and established investigations.

PMID- 16810435
TI  - Operative workload of a paediatric otolaryngology department over a five-year
      period.
AB  - INTRODUCTION: The KK Women's and Children's Hospital (KKWCH) is Singapore's only
      tertiary institution dedicated wholly to the provision of healthcare for women
      and children. Since its opening in 1997, the clinical caseloads and the
      complexity of medical conditions managed by the various departments has increased
      considerably. This review aims to analyse the operative caseloads in the
      Department of Otolaryngology over five years from 2000 to 2004. METHODS: This is
      a retrospective review of the KKWCH Department of Otolaryngology operative
      records from year 2000 to 2004. The data on the type of operation and their
      frequency were collated, and the data are presented in a descriptive format.
      RESULTS: There was an increase in the number of operations performed from 656 in
      year 2000 to 1,148 in 2004, an increase of 75 percent. The increase in the
      staffing and operating clinical hours (in 2003 and 2004) plus the significant
      demand for paediatric otolaryngology service probably contributed to this
      increase. Tonsillectomy, with or without adenoidectomy, continues to be the most
      common procedure being performed in children, with myringotomy and tympanostomy
      tube insertion being the second commonest. Together, the ten most common
      operative procedures constitute 78.2 percent of all paediatric otolaryngological
      operative workload in the department over a five-year period. CONCLUSION: The
      data provided a review of the current pattern of otolaryngological surgical
      disease in the Singapore paediatric population, which may require operative
      intervention. Understanding and monitoring of this trend is important, as it
      allows the proper allocation of appropriate resources for the prevention and
      treatment of common paediatric surgical otolaryngological conditions.

PMID- 16810436
TI  - Pseudoretinoblastoma in enucleated eyes of Asian patients.
AB  - INTRODUCTION: Retinoblastomas of the eye are a cause of childhood blindness and
      have a high rate of mortality, as well as a hereditary mode of transmission.
      Other conditions that mimic retinoblastomas are known as pseudoretinoblastomas,
      and are managed differently. Although pseudoretinoblastoma and the accuracy of
      retinoblastoma diagnosis have been reviewed in Caucasian patients, published
      studies in Asian patients are lacking. The purpose of this article is to report
      our experience with pseudoretinoblastomas in two major ophthalmological centres
      in Asia. METHODS: A case series of 28 enucleations carried out for suspected
      retinoblastoma at the Singapore National Eye Centre and KK Women's and Children's
      Hospital, Singapore, between January 1991 and December 2002, is reported. All
      cases were subjected to a detailed history from parents, followed by external
      ocular examination, slit-lamp biomicroscopy and binocular indirect
      ophthalmoscopy. Ancillary studies, such as B-scan ultrasonography and computed
      tomography, were employed as necessary to confirm the diagnosis. Histology was
      obtained on all cases. RESULTS: Of the 28 cases, 25 (89 percent) were found on
      histological analysis to be retinoblastomas. Three (11 percent) were
      pseudoretinoblastomas. There were two cases of Coat's disease and a case of
      presumed ocular toxocariasis. These three cases were described in detail.
      CONCLUSION: Although our sample size is small, the percentage of confirmed
      retinoblastomas was found to be only slightly higher than that found in western
      countries. Our findings are consistent with their findings that Coat's disease
      and presumed ocular toxocariasis are the more common causes of
      pseudoretinoblastoma.

PMID- 16810437
TI  - The in-vitro activity of colistin in gram-negative bacteria.
AB  - INTRODUCTION: Colistin is a polypeptide antibiotic belonging to the polymyxins,
      and has been increasingly used for the treatment of multiresistant gram-negative
      infections. There is little current available data on the susceptibility of gram
      negative bacilli to colistin, in part because susceptibility testing for colistin
      remains problematic, and also because the use of colistin is not widespread. This
      study tested clinical isolates of gram-negative bacilli for susceptibility to
      colistin using the reference susceptibility testing method of agar dilution.
      METHODS: 102 strains of gram-negative bacilli were collected over a one-year
      period. Antibiotic susceptibility profiles were derived from disc susceptibility
      testing, and organisms were identified by standard microbiological methods.
      Isolates were selected for inclusion in the study using susceptibility profiles
      and epidemiological data. Minimum inhibitory concentrations to colistin were
      obtained by performing agar dilution according to a standardised method. RESULTS:
      30 percent of tested isolates were resistant to colistin. All Acinetobacter spp.
      and Escherichia coli were susceptible to colistin. Colistin resistance was
      detected predominantly in Stenotrophomonas maltophilia and Pseudomonas
      aeruginosa, but was also present in Enterobacter spp. and Klebsiella spp.
      CONCLUSION: Colistin resistance is uncommon in the Enterobacteriaceae, but
      present in a significant proportion of S. maltophilia and P. aeruginosa isolates.
      From the results of this study, we recommend that susceptibility testing be
      performed whenever the clinical use of the polymyxins is considered.

PMID- 16810438
TI  - Hereditary neuropathy with liablity to pressure palsies.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is a disease that
      presents with recurrent reversible episodes of neurapraxia that occur typically
      after trivial trauma. It is an autosomal dominant, demyelinating neuropathy. A 20
      year-old man presented with left ulnar nerve palsy after a fall. He had reduced
      two-point discrimination over his left ulnar nerve distribution, with mild
      clawing of the ring and little fingers, and accompanying weakness of the first
      dorsal interrosseus and abductor digiti minimi of grade four power. His Froment's
      sign was also positive. Careful clinical examination and appropriate tests,
      including electromyography and genetic testing, confirmed the diagnosis of HNPP.
      This case report is presented to promote awareness and recognition of this
      disease in the local and regional context.

PMID- 16810439
TI  - Endolymphatic sac tumour: a rare cause of recurrent vertigo.
AB  - Endolymphatic sac tumour occurring in a 32-year-old man presenting with Meniere's
      like symptoms of recurrent vertigo, hearing loss and tinnitus is described.
      Magnetic resonance imaging and computed tomography showed a vascular bone tumour
      centred over the retrolabyrinthine aspect of the temporal bone where the
      endolymphatic sac was located. Surgical excision via a translabyrinthine approach
      was performed. Endolymphatic sac tumours are rare papillary adenocarcinomas that
      arise from the endolympatic sac. It can be mistaken both on radiology and
      histology for other tumours such as paragangliomas, renal or papillary thyroid
      carcinoma metastases. Surgical excision is the treatment of choice but sacrifice
      of the auditory and facial nerve may be needed in advanced cases to achieve
      tumour clearance.

PMID- 16810440
TI  - Monocular blindness: a complication of intraoperative positioning in posterior
      cervical spine surgery.
AB  - Postoperative visual loss after spine surgery is a rare but devastating
      complication. Although uncommon, reports of postoperative blindness are
      documented in spine and cardiopulmonary bypass surgeries with an incidence
      varying between 0.05 percent and one percent. A 62-year-old man presenting with
      cervical myelopathy underwent C3-C6 posterior laminectomy, decompression and
      lateral mass plating. Unfortunately, he developed unilateral blindness in his
      right eye. The potential aetiological factors and ways to prevent this disastrous
      complication are discussed.

PMID- 16810441
TI  - Artifacts in mammography: ways to identify and overcome them.
AB  - High-quality mammography images enhance a radiologist's ability to interpret
      mammograms because they have greater sensitivity and specificity. Artifacts may
      create pseudo-lesions or mask abnormalities leading to misinterpretation.
      Familiarity with the numerous artifacts encountered will enable radiologists to
      provide accurate diagnoses. We reviewed all the artifacts in mammography
      encountered at our centres and classified the causes of these artifacts into four
      categories. They are: 1. patient-related; 2. technologist-related; 3. related to
      the mammographic unit; and 4. related to processing and the processor.
      Implementation of a well-organised quality control programme will reduce the
      occurrence of artifacts. Recognition of artifacts in mammography is instructive
      and will help to improve the mammographic diagnostic quality.

PMID- 16810442
TI  - Clinics in diagnostic imaging (110). Right-sided tubal ligation clips complicated
      by the formation of an infected retention cyst.
AB  - A 35-year-old Chinese woman presented with a five-day history of right iliac
      fossa pain and mass. She had no significant past medical history apart from
      laparoscopic tubal ligation performed years ago. Pelvic ultrasonography
      demonstrated a well-rounded cystic mass with homogeneous internal echoes and a
      brightly echogenic component, compatible with tubal ligation clips. Right adnexal
      infected retention cyst secondary to tubal ligation clips was diagnosed.
      Complications of female sterilisation are rare but nevertheless have been
      reported and accounted for symptoms of lower abdominal pain, and should be
      considered as a differential diagnosis.

PMID- 16810443
TI  - Serious cutaneous adverse reactions to traditional Chinese medicines.

PMID- 16810446
TI  - Doppler tissue imaging evaluation of right ventricular function at rest and
      during dobutamine infusion in patients after repair of tetralogy of Fallot.
AB  - BACKGROUND: Reliable, non-invasive evaluation of right ventricular function,
      especially in congenital heart disease, is challenging. OBJECTIVES: The aim of
      this study was to evaluate Doppler tissue imaging (DTI) parameters of lateral
      tricuspid annular motion, mean rate of pressure rise during RV contraction (mean
      dP/dt) and indexed right ventricular (RV) stroke volume (RVSVi) as RV function
      indices in repaired tetralogy of Fallot (TOF). METHODS: DTI evaluation was
      performed in 25 repaired-TOF patients, aged 11+/-6, at rest and during dobutamine
      infusion and 20 controls at rest. RESULTS: TOF patients had lower (P<0.05) peak
      systolic velocity (Sa) (11.4+/-4 vs. 13.7+/-3.1 cm/s), early diastolic velocity
      (Ea) (11+/-3.1 vs. 16.3+/-3.5 cm/s) and Sa/time from onset of QRS to Sa (Sa/Q-Sa)
      (68.8+/-26.4 vs. 92.3+/-29.4 cm/s2) versus controls. Dobutamine increased
      (P<0.01) Sa (11.4+/-2.8-17.7+/-4.7 cm/s), Ea (11+/-3.1-15.6+/-3.9 cm/s), late
      diastolic velocity (Aa) (8.4+/-2-14.8+/-5 cm/s), Sa/Q-Sa (68.8+/-26.4-17 6.8+/
      84.5 cm/s2), mean dP/dt (180+/-74-537+/-37 2 mmHg/s), and RVSVi (7.8+/-3.9-11.9+/
      5.6 L/min/m2). RVSVi increase correlated (P<0.01) with that in Sa (r=0.6), Ea
      (r=0.5), Sa/Q-Sa (r=0.71), and mean dP/dt (r=0.57) while mean dP/dt increase
      correlated strongly with Sa/Q-Sa increase (r=0.88). CONCLUSION: DTI evaluation of
      tricuspid annular motion during dobutamine infusion in repaired TOF correlates
      with dP/dt and RV stroke volume and may help in assessing RV function and
      reserve.

PMID- 16810447
TI  - Angiographic segment size in patients referred for coronary intervention is
      influenced by constitutional, anatomical, and clinical features.
AB  - BACKGROUND: Factors influencing the size of target vessels of patients referred
      for coronary intervention are poorly defined. We aimed to investigate in a large
      series of patients undergoing percutaneous intervention the relation of
      constitutional, anatomical, and clinical features with the reference diameter of
      coronary vessels treated with stenting. METHODS: A total of 4,850 de novo
      coronary lesions, non-ostial and non-bifurcational, located in native vessels
      were analyzed. The following pre-specified characteristics were analyzed to
      reflect the relation between constitutional, anatomical, and clinical features on
      reference vessel diameter: age, gender, height, weight, proximal location,
      vessel, diabetes, hypertension, multivessel disease, and clinical presentation.
      RESULTS: The average reference diameter was 2.66+/-0.50 mm. All pre-specified
      markers had a significant relation with the vessel reference diameter at
      univariate analysis, except by hypertension which showed a strong tendency.
      However, at multivariate analysis, only diabetes, proximal location, multivessel
      disease, clinical presentation, vessel, weight, and height were identified as
      independent predictors of reference vessel diameter. CONCLUSION: Reference
      diameter of coronary vessels at the site of lesions treated by stenting is
      significantly influenced by a variety of characteristics. We hypothesize that the
      treated segment size of patients undergoing stenting ultimately reflects the
      conjoint effect of several different factors, including constitutional,
      anatomical, and clinical features.

PMID- 16810448
TI  - Non-invasive computed tomography coronary angiography: a reliable gatekeeper for
      conventional angiography in patients referred for valve surgery?

PMID- 16810449
TI  - Molecular cloning and expression of yak (Bos grunniens) lactoferrin cDNA in
      Pichia pastoris.
AB  - cDNA encoding lactoferrin from yak was isolated by RT-PCR and then sequenced. The
      cloned cDNA (2127 bp) encodes a 709 amino acid precursor molecule of yak
      lactoferrin with a signal peptide of 19 amino acids. The yak lactoferrin cDNA was
      expressed in Pichia pastoris. The recombinant protein, purified by Ni-NTA
      affinity column, had a molecular weight of 76 kDa and reacted with an antibody
      raised against native bovine lactoferrin. The iron-binding behavior and
      antimicrobial activity of the purified protein indicated that it was correctly
      folded and functional.

PMID- 16810450
TI  - Enhancement of xylitol productivity and yield using a xylitol dehydrogenase gene
      disrupted mutant of Candida tropicalis under fully aerobic conditions.
AB  - The effects of glycerol and the oxygen transfer rate on the xylitol production
      rate by a xylitol dehydrogenase gene (XYL2)-disrupted mutant of Candida
      tropicalis were investigated. The mutant produced xylitol near the almost yield
      of 100% from D: -xylose using glycerol as a co-substrate for cell growth and
      NADPH regeneration: 50 g D: -xylose l(-1) was completely converted into xylitol
      when at least 20 g glycerol l(-1) was used as a co-substrate. The xylitol
      production rate increased with the O(2) transfer rate until saturation and it was
      not necessary to control the dissolved O(2) tension precisely. Under the optimum
      conditions, the volumetric productivity and xylitol yield were 3.2 g l(-1) h(-1)
      and 97% (w/w), respectively.

PMID- 16810451
TI  - Desulfurization of dibenzothiophene by Bacillus subtilis recombinants carrying
      dszABC and dszD genes.
AB  - The desulfurization (dsz) genes from Rhodococcus erythropolis DS-3 were
      successfully integrated into the chromosomes of Bacillus subtilis ATCC 21332 and
      UV1 using an integration vector pDGSDN, yielding two recombinant strains, B.
      subtilis M29 and M28 in which the integrated dsz genes were expressed efficiently
      under the promoter, Pspac. The dibenzothiophene (DBT) desulfurization efficiency
      of M29 was 16.2 mg DBT l(-1) h(-1) at 36 h, significantly higher than that of R.
      erythropolis DS-3 and B. subtilis M28 and also showed no product inhibition. The
      interfacial tension of the supernatant fermented by M29 varied from 48 mN m(-1)
      to 4.2 mN m(-1), lower than that of the recombinant strain, M28, reveals that the
      biosurfactant secreted from M29 may have an important function in the DBT
      desulfurization process.

PMID- 16810452
TI  - Studying and evaluating pharmaceutical policy--becoming a part of the policy and
      consultative process.
AB  - In this last article in the series the authors focus on the issue of researching
      and evaluating pharmaceutical policy. The past five articles made an argument for
      why pharmaceutical policy is important and why it is different from health
      policy. The evidence base needed for pharmaceutical policymaking is also somewhat
      specialized in relation to health policy. Taking these differences into
      consideration the authors provide their definition of pharmaceutical policy. The
      knowledge base for good pharmaceutical policymaking needs to be broad and include
      approaches and methodologies ranging from the highly quantitative and
      experimental to the purely qualitative. Other policy questions such as those
      concerned with rational use of medicines and economics illustrate that
      pharmaceutical policy needs more varied approaches than randomized clinical
      trials alone can provide. The importance of gaining a thorough overview and
      understanding of the available design and methodological options for policy
      analysis is emphasized. Research into pharmaceutical policy has many
      commonalities with evaluation and policy analysis. Some of the main pitfalls that
      policymakers, researchers and analysts can fall into when formulating and
      evaluating pharmaceutical policy are discussed and include: using too narrow
      evaluation questions; choosing inappropriate methods/designs; and the problem of
      bias and self-censorship. The authors conclude this series by advocating a strong
      focus on research and an international evaluation culture around pharmaceutical
      policy. They emphasize the importance of pharmaceutical specialists' (i.e.,
      pharmacists') involvement in pharmaceutical policy analysis and the policy
      consultative process.

PMID- 16810453
TI  - Effect of head-tail ratio and the range of the head-head interaction in
      amphiphilic self-assembly.
AB  - We investigate cluster autocorrelations, critical micelle concentration (CMC),
      and size distribution for amphiphiles of the type H(x)T(y) as a function of the
      amphiphilic factor alpha = x/y for a fixed length l = x + y using a combination
      of reptation and kink-jump Monte Carlo (MC) moves in a two-dimensional (2D)
      square lattice. We find that the CMC decreases monotonically as a function of the
      alpha-parameter. For a fixed chain length l of the molecule, the symmetric
      molecules of the type H(l/2)T(l/2) with alpha = 1 tend to form circular micelles
      with relatively narrow distribution in cluster sizes. As we decrease the alpha
      parameter to introduce head-tail asymmetry, the size distribution becomes
      polydisperse with occurrences of more elongated micelles. A calculation of the
      cluster autocorrelation function reveals that for the same chain length,
      symmetric amphiphiles take significantly less time to equilibrate and therefore
      simulation of much longer molecules is possible. Next we study the effect of the
      head-head repulsion term beyond next nearest neighbors. In general, the presence
      of a longer-range repulsive interaction reduces the average size of the micelles.
      We also notice that for l = 5, while H(2)T(3) molecules produces spherical
      micelles, the H(1)T(4) molecules( alpha = 0.25) often form vesicles. Our
      systematic studies bring out relevant information for controlling shapes and
      sizes of micelles to be used as templates in the design of self-assembled
      nanostructures.

PMID- 16810455
TI  - Natural sweet macromolecules: how sweet proteins work.
AB  - A few proteins, discovered mainly in tropical fruits, have a distinct sweet
      taste. These proteins have played an important role towards a molecular
      understanding of the mechanisms of taste. Owing to the huge difference in size,
      between most sweeteners and sweet proteins, it was believed that they must
      interact with a different receptor from that of small molecular weight
      sweeteners. Recent modelling studies have shown that the single sweet taste
      receptor has multiple active sites and that the mechanism of interaction of sweet
      proteins is intrinsically different from that of small sweeteners. Small
      molecular weight sweeteners occupy small receptor cavities inside two subdomains
      of the receptor, whereas sweet proteins can interact with the sweet receptor
      according to a mechanism called the 'wedge model' in which they bind to a large
      external cavity. This review describes these mechanisms and outlines a history of
      sweet proteins.

PMID- 16810454
TI  - Device-specific thresholds to diagnose osteoporosis at the proximal femur: an
      approach to interpreting peripheral bone measurements in clinical practice.
AB  - INTRODUCTION: A single T score criterion cannot be universally applied to
      different peripheral bone measurement devices, since measurements in an identical
      population result in a tenfold difference in the prevalence of osteoporosis. The
      use of peripheral devices is increasing in clinical practice, despite the
      difficulties in interpreting results. We propose the use of two thresholds, which
      have either 95% sensitivity or 95% specificity, to identify (1) individuals who
      require treatment or (2) individuals who require no treatment, both based on a
      peripheral measurement alone, or (3) individuals who require additional central
      densitometry measurements. METHODS: We recruited 500 postmenopausal women, 100
      premenopausal women and 279 women with proximal femoral, vertebral, distal
      forearm or proximal humeral fractures. All subjects underwent dual energy X-ray
      absorptiometry (DXA) measurements of the lumbar spine, total hip and distal
      forearm, quantitative computed tomography (QCT) of the distal forearm and
      quantitative ultrasound (QUS) of the heel (four devices), finger (two devices),
      radius and metatarsal. We identified the threshold for each device that
      identified women without osteoporosis with the same sensitivity (upper threshold
      set at 95%) as total hip DXA and women with osteoporosis with the same
      specificity (lower threshold set at 95%) as total hip DXA. Individuals between
      the two thresholds required additional examination by central densitometry.
      RESULTS: The correlation between devices varied from 0.173 (QUS finger) to 0.686
      (DXA forearm) compared with total hip DXA (P<0.0001). The area under the curve
      (AUC) between devices varied from 0.604 (QUS finger) to 0.896 (DXA forearm)
      compared with total hip DXA (P<0.0001). In a population-based cohort (prevalence
      of osteoporosis 9.8%) the threshold approach appropriately identified between 26%
      (QUS heel) and 68% (DXA forearm) of subjects in whom a treatment decision could
      be made without additional central DXA with 95% certainty. In a fracture cohort
      (prevalence of osteoporosis 36%) between 16% (QUS finger) and 37% (QCT forearm)
      of subjects were appropriately identified. CONCLUSION: The threshold approach to
      interpreting peripheral bone measurements enables a substantial number of
      individuals with either normal bone mineral density (BMD) or osteoporosis to be
      selected and treated appropriately.

PMID- 16810456
TI  - Potassium-related inherited tubulopathies.
AB  - Hyper- and hypokalemia may carry severe clinical consequences. Different
      regulatory mechanisms, including the kidney, exert a tight regulation of plasma
      potassium levels. The renal pathway of potassium handling begins in the proximal
      tubule followed by the fine-tuning of its secretion or absorption at the distal
      tubule, including the thick ascending limb of Henle's loop, the distal convoluted
      tubule and the cortical collecting duct. Genetic studies in recent years have
      clarified the role of specific tubular channels and transporters in the
      pathogenesis of unique hyper- and hypokalemic tubulopathies, some of them non
      hypertensive (pseudohypoaldosteronism, Bartter and Gitelman syndromes) and others
      hypertensive by definition (including Liddle and Gordon syndromes). This article
      reviews the genetic and clinical spectrum of hypokalemic and hyperkalemic
      tubulopathies.

PMID- 16810457
TI  - The neurobiology of Williams syndrome: cascading influences of visual system
      impairment?
AB  - Williams syndrome (WS) is characterized by a unique pattern of cognitive,
      behavioral, and neurobiological findings that stem from a microdeletion of genes
      on chromosome 7. Visuospatial ability is particularly affected in WS and
      neurobiological studies of WS demonstrate atypical function and structure in
      posterior parietal, thalamic, and cerebellar regions that are important for
      performing space-based actions. This review summarizes the neurobiological
      findings in WS, and, based on these findings, we suggest that people with WS have
      a primary impairment in neural systems that support the performance of space
      based actions. We also examine the question of whether impaired development of
      visual systems could affect the development of atypical social-emotional and
      language function in people with WS. Finally, we propose developmental
      explanations for the visual system impairments in WS. While hemizygosity for the
      transcription factor II-I gene family probably affects the development of visual
      systems, we also suggest that Lim-kinase 1 hemizygosity exacerbates the
      impairments in performing space-based actions.

PMID- 16810458
TI  - Cloning and sequencing analysis of alginate lyase genes from the marine bacterium
      Vibrio sp. O2.
AB  - We isolated a new marine bacteria, which displayed alginate-depolymerizing
      activity in plate assays, from seawater in Mihonoseki Harbor, Japan. Analysis of
      the 16S ribosomal RNA gene sequence of one of the isolates proved that this
      alginate-depolymerizing bacterium belonged to the genus Vibrio and it was named
      Vibrio sp. O2. The alginate lyase genes of Vibrio sp. O2 were cloned and
      expressed in Escherichia coli. Two alginate lyase-producing clones, pVOA-A4 and
      pVOA-B5, were obtained. The alginate lyase gene alyVOA from pVOA-A4 was composed
      of an 858-bp open reading frame (ORF) encoding 285 amino acid residues, while
      alyVOB from pVOA-B5 was composed of an 828-bp ORF encoding 275 amino acid
      residues. The degree of identity between the deduced amino acid sequences of
      AlyVOA or AlyVOB and Photobacterium sp. ATCC43367 alginate poly(ManA)lyase AlxM
      was 92.3% or 32.6%, respectively. Alginate lyase consensus regions corresponding
      to the sequences YFKAGXYXQ and RXELR were observed in all three of these
      sequences. AlyVOA and AlyVOB both degraded polymannuronate in plate assays and
      were therefore confirmed to be poly(beta-D-mannuronate)lyases.

PMID- 16810459
TI  - Management of severe hemoptysis from pulmonary aspergilloma using endovascular
      embolization.
AB  - PURPOSE: To determine the effectiveness of endovascular embolization as a
      temporizing measure in the management of severe hemoptysis caused by
      intracavitary pulmonary aspergilloma. METHODS: Patients presenting with
      hemoptysis, estimated to be more than 300 ml in the preceding 24 hr, in whom a
      radiological diagnosis of pulmonary aspergilloma was made on chest radiographs
      and/or computed tomography of the chest were subjected to bronchial and systemic
      arteriography and embolization using triacryl microspheres. RESULTS: Twelve
      patients with upper lobe intracavitary aspergillomas were managed with
      embolization. In 11 patients hemoptysis stopped within 24 hr and with no
      recurrence over the next 4 weeks. In 1 patient hemoptysis persisted and an upper
      lobe lobectomy was performed. CONCLUSION: Embolization of bronchial and systemic
      arteries is an effective method for treating acute severe hemoptysis from
      intracavitary aspergillomas, allowing the patient time to recover for definitive
      surgical management.

PMID- 16810460
TI  - Transjugular intrahepatic portosystemic shunt creation in Budd-Chiari syndrome:
      percutaneous ultrasound-guided direct simultaneous puncture of the portal vein
      and vena cava.
AB  - Budd-Chiari syndrome (BCS) is an uncommon disorder that can be life-threatening,
      depending on the degree of hepatic venous outflow obstruction. Transjugular
      intrahepatic portosystemic shunt (TIPS) provides decompression of the congested
      liver but the hepatic vein obstruction makes the procedure more difficult. We
      describe a modified method that involved a single percutaneous puncture of the
      portal vein and inferior vena cava simultaneously for TIPS creation in a patient
      with BCS.

PMID- 16810461
TI  - Venous thromboembolism after uterine fibroid embolization.
AB  - Thromboembolic complications after uterine fibroid embolization (UFE) are
      infrequent. The incidence and predisposing factors of thromboembolism after UFE
      are unknown. We present eight cases of nonfatal thromboembolic complications
      after UFE and estimate the frequency of such events as 0.4%.

PMID- 16810462
TI  - Thromboelastographic changes following nonionic contrast medium injection during
      transfemoral angiography in patients with peripheral arterial occlusive disease.
AB  - BACKGROUND/PURPOSE: Patients with peripheral arterial occlusive disease (PAOD)
      are known to be systemically hypercoagulable and there is concern that exposing
      them to contrast media during angiography may exacerbate that thrombotic
      tendency. Many in vitro studies in which blood is exposed to contrast media
      suggest that nonionic contrast medium (NICM) has a weaker anticoagulant effect
      than ionic contrast medium (ICM) and some studies suggest that NICM can lead to
      activation of coagulation thus increasing the risk of thrombotic events where it
      is employed. We have looked at the changes in coagulation adjacent to the site of
      contrast injection/potential angioplasty to determine the magnitude of change
      locally. METHODS: We measured changes in the coagulability of aortic blood
      samples immediately before and within 2 min after injection of the last bolus of
      iohexol (NICM) prior to any intervention procedure in 30 patients with PAOD.
      Samples were analyzed using thromboelastography (TEG) to identify changes in the
      coagulability of the aortic blood samples. RESULTS: TEG tracings of samples taken
      from the aorta after injection of NICM showed a significant increase in R time
      (time to fibrin formation) (p = 0.036) and in k time (dynamics of clot formation)
      (p = 0.028) and a reduction in Angle (decreased acceleration of fibrin build-up)
      (p = 0.013), Maximal amplitude (MA) (reduced ultimate clot strength) (p = 0.018)
      and Coagulation Index (CI) (p = 0.032). CONCLUSION: These changes in TEG
      parameters show that the local effect of NICM is a reduction in coagulation
      activity rather than the activation suggested by some previous studies.

PMID- 16810463
TI  - Regulation of sympathetic nerve traffic to skeletal muscle in resting humans.
AB  - An overview is given of microneurographic studies of resting vasoconstrictor
      traffic in human muscle nerves (muscle sympathetic nerve activity = MSNA). In
      multiunit recordings, the activity consists of synchronized bursts of
      vasoconstrictor impulses, the outflow of which is under potent arterial
      baroreflex control. In agreement with this, the bursts always display cardiac
      rhythmicity and occur during temporary reductions of blood pressure. Burst
      occurrence shows a close inverse correlation to variations of diastolic blood
      pressure whereas the correlation to the strength of the bursts is weak or absent,
      suggesting that the mechanisms controlling the two parameters are not identical.
      These dynamic characteristics are similar in all subjects despite large,
      reproducible, interindividual differences in number of bursts. Such
      interindividual differences probably have a genetic origin, and since discharge
      frequencies in single vasoconstrictor fibers are similar in subjects with few and
      many bursts, the differences in multiunit activity are likely to be due to a
      higher number of active fibers in subjects with many bursts. The interindividual
      differences in multiunit activity are not associated with differences in resting
      blood pressure levels. Recent studies have revealed (a) an inverse relationship
      between resting levels of cardiac output and MSNA and (b) evidence of reduced
      vascular responsiveness to noradrenaline in subject with many sympathetic bursts
      at rest. These findings suggest that the vasoconstriction induced by the
      sympathetic impulses is balanced or reduced by these factors, which thereby
      contribute to the poor relationship between the mean number of sympathetic bursts
      and the blood pressure level.

PMID- 16810464
TI  - Calcium polycarbophil improves constipation in non-traumatic spinal cord
      disorders.
AB  - Calcium polycarbophil shortened total colonic transit time (P < 0.05), increased
      bowel frequency and improved defecation difficulty in four patients with non
      traumatic spinal cord disorders. Polycarbophil may be useful for the treatment of
      constipation.

PMID- 16810465
TI  - Effect of hyperglycemic condition on proteoglycan secretion in cultured human
      endothelial cells.
AB  - BACKGROUND: Proteoglycans (PGs) are important constituents of the plasma membrane
      and of the basement membrane supporting the endothelial cell layer. Changes in
      the amounts or the structures of PGs in the endothelium may affect important
      functions such as turnover of lipoproteins, filtration properties, and regulation
      of chemokines during inflammation, which are all relevant in diabetes. AIM OF THE
      STUDY: The purpose of this study was to investigate if hyperglycemic conditions
      would affect the biosynthesis and secretion of PGs in cultured primary human
      endothelial cells. METHODS: Primary human umbilical cord vein endothelial cells
      were established and cultured in vitro. The cells were cultured either in medium
      with low glucose (LG) (1 g/l) or high glucose (HG) (4.5 g/l). From day 3-4 cells
      were labeled with (35)S-sulfate for 24 h. (35)S-Labeled macromolecules (medium)
      were purified by gel chromatography, and isolated macromolecules were analyzed by
      gel chromatography after different types of treatment, electrophoresis, and
      immunoprecipitation. RESULTS: Lower levels of secreted PGs were found in human
      endothelial cells exposed to HG. The major part of the PGs released was of the
      heparan sulfate (HS) type, and immunoprecipitation experiments showed that one
      such PG was syndecan-1. However, there was no difference in the ratio between HS
      and chondroitin sulfate (CS) under the different experimental conditions.
      Further, the PGs expressed neither differ with regard to molecular size of the
      glycosaminoglycan (GAG) chains, nor were their polyanionic properties affected by
      the different experimental conditions. CONCLUSION: The results obtained suggest
      that treatment of primary human endothelial cells with hyperglycemia leads to a
      decrease in PG secretion in primary cultures of human endothelial cells.

PMID- 16810467
TI  - ["Under pressure" -- the clinical relevance of hypertension for the heart and
      circulation].

PMID- 16810466
TI  - The recovery of 13C-labeled oleic acid in rat lymph after administration of long
      chain triacylglycerols or specific structured triacylglycerols.
AB  - BACKGROUND: Consumption of specific structured triacylglycerols, MLM (M = medium
      chain fatty acid, L = long chain fatty acid), delivers fast energy and long chain
      fatty acids to the organism. AIM OF THE STUDY: The purpose of the present study
      was to compare lymphatic absorption of (13)C-labeled MLM and (13)C-labeled LLL in
      rats. Stable isotope labeling enables the separation of the endogenous and
      exogenous fatty acids. METHODS: Lymph was collected during 24 h following
      administration of MLM or LLL. Lymph fatty acid composition and (13)C-enrichment
      were determined and quantified by gas chromatography combustion isotope ratio
      mass spectrometry. RESULTS: The recovery of 18:1n-9 was higher after
      administration of LLL compared with MLM (58.1% +/- 7.4% and 29.1% +/- 3.9%,
      respectively, P < 0.001). This may be due to a higher chylomicron formation
      stimulated by a higher amount of long chain fatty acids in the intestine after
      LLL compared with MLM administration. This was confirmed by the tendencies of
      higher lymphatic transport of endogenous fatty acids. CONCLUSION: The study
      revealed a higher lymphatic recovery of the administered long chain fatty acids
      after LLL compared with MLM consumption.

PMID- 16810468
TI  - [Epidemiology of hypertension in Germany and worldwide].
AB  - Hypertension represents a major risk factor for myocardial infarction and the
      most important risk factor for stroke. Two thirds of strokes and half of
      myocardial infarctions arise from a systolic blood pressure > 115 mmHg. The
      relationship between blood pressure and cardiovascular diseases is log linear.
      Hypertension is the leading risk factor of preventable deaths worldwide. High
      blood pressure accounts for 26% of the total mortality in Germany. The prevalence
      of hypertension in Germany (55%) is twice the rate in Canada and the USA. Health
      care indicators such as hypertension awareness, treatment and control in Germany
      trail behind when compared internationally. Hypertension treatment and control in
      Germany amount to 26% and 8%, respectively. Concepts for the improvement of
      health care in patients with high blood pressure are, e.g., improvement of
      guideline awareness among physicians as well as quality-oriented payment for
      health care.

PMID- 16810469
TI  - [Pathophysiology of hypertension: what's new?].
AB  - The pathophysiology of primary hypertension is still unresolved and appears more
      complex than ever. It is beyond the scope of this article to review all new
      scientific developments in this field. On clinical grounds, hypertension is
      divided into primary and secondary forms. Here, the authors discuss the
      pathophysiology of hypertension associated with three common disease entities
      showing a large overlap with primary hypertension: chronic kidney disease (CKD),
      obstructive sleep apnea (OSA), and hyperaldosteronism. Especially in CKD and OSA,
      the activation of the sympathetic nervous system plays a crucial role. It is the
      authors' belief that hypertension due to these three diseases is more common than
      previously appreciated and may account for about 20% of the hypertensive
      population. The knowledge of the underlying pathophysiology allows early
      diagnosis and guides optimal treatment of these hypertensive patients.

PMID- 16810470
TI  - Ventricular hypertrophy and hypertension: prognostic elements and implications
      for management.
AB  - Left ventricular hypertrophy (LVH) is a strong, independent predictor of
      cardiovascular events and all-cause mortality. Patients with LVH are at increased
      risk for stroke, coronary heart disease, congestive heart failure, and sudden
      cardiac death. Hypertension is a major influence on the development of LVH. The
      prognostic power of LVH is likely multifactorial. LVH represents both a
      manifestation of the effects of hypertension and other cardiac risk factors over
      time as well as an intrinsic condition causing pathologic changes in cardiac
      structure and function. Angiotensin II plays a central role in the development of
      LVH. Several antihypertensive treatments, especially angiotensin II receptor
      blockers, can reverse LVH and improve cardiovascular outcomes independent of
      blood pressure reduction. Further studies are required to determine if these
      agents should become first-line therapy for all patients with hypertension and
      LVH.

PMID- 16810471
TI  - [Kidney and hypertension].
AB  - The regulation of blood pressure is a complex process, involving several organs.
      The kidney plays a major role and is involved in the initiation and maintenance
      of hypertension. Mechanisms involved are: (1) the sympathetic nerveous system,
      (2) the renin-angiotensin system, (3) the regulation of sodium and water balance,
      (4) the production of vasoactive substances such as endothelin, adenosine or
      nitric oxide (NO), and (5) structural alterations such as a reduced number of
      glomeruli and nephrons. Several therapeutic intervention strategies affecting
      these mechanisms have already proven to be effective antihypertensive drugs.

PMID- 16810472
TI  - Are all the hypertensives made equal?
AB  - Blood pressure lowering in hypertensive patients is of significant importance.
      The complex pathophysiology makes the therapeutic targets many, and extensive
      research has provided us with many antihypertensive drugs. However, data indicate
      that the proportion of patients with controlled blood pressure is far from
      satisfying. This may partly be explained by a lack of individualized treatment.
      Present guidelines for management of hypertension emphasize that a thorough
      evaluation of the patient is necessary before initiating treatment. Based on
      information about gender, age, ethnicity, family history, clinical examination
      and concomitant diseases like diabetes mellitus, coronary heart disease, heart
      failure, cerebrovascular disease and gout, the physician is able to provide the
      best treatment. However, most patients need two to three drugs to control the
      blood pressure. Thus, we need methods to predict blood pressure responses to the
      various drugs in the individual patients. Possibly, in the future treatments may
      be based upon genetic variants. Until now, several polymorphisms in genes
      regulating blood pressure have been located, and these may influence responses to
      drugs. However, the results are heterogeneous and contradictory, and we are yet
      not capable of determining the best treatment based on genetic properties. Coming
      years challenge us to further clarify these potentially important aspects of
      treatment. Meanwhile, physicians are obligated to individualize the treatment by
      other means, based on disease history, concomitant diseases and clinical
      examination.

PMID- 16810473
TI  - ESH-ESC guidelines for the management of hypertension.
AB  - The following is a brief statement of the 2003 European Society of Hypertension
      (ESH)-European Society of Cardiology (ESC) guidelines for the management of
      arterial hypertension. The continuous relationship between the level of blood
      pressure and cardiovascular risk makes the definition of hypertension arbitrary.
      Since risk factors cluster in hypertensive individuals, risk stratification
      should be made and decision about the management should not be based on blood
      pressure alone, but also according to the presence or absence of other risk
      factors, target organ damage, diabetes, and cardiovascular or renal damage, as
      well as on other aspects of the patient's personal, medical and social situation.
      Blood pressure values measured in the doctor's office or the clinic should
      commonly be used as reference. Ambulatory blood pressure monitoring may have
      clinical value, when considerable variability of office blood pressure is found
      over the same or different visits, high office blood pressure is measured in
      subjects otherwise at low global cardiovascular risk, there is marked discrepancy
      between blood pressure values measured in the office and at home, resistance to
      drug treatment is suspected, or research is involved. Secondary hypertension
      should always be investigated. The primary goal of treatment of patient with high
      blood pressure is to achieve the maximum reduction in long-term total risk of
      cardiovascular morbidity and mortality. This requires treatment of all the
      reversible factors identified, including smoking, dislipidemia, or diabetes, and
      the appropriate management of associated clinical conditions, as well as
      treatment of the raised blood pressure per se. On the basis of current evidence
      from trials, it can be recommended that blood pressure, both systolic and
      diastolic, be intensively lowered at least below 140/90 mmHg and to definitely
      lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg
      in diabetics. Lifestyle measures should be instituted whenever appropriate in all
      patients, including subjects with high normal blood pressure and patients who
      require drug treatment. The purpose is to lower blood pressure and to control
      other risk factors and clinical conditions present. In most, if not all,
      hypertensive patients, therapy should be started gradually, and target blood
      pressure achieved progressively through several weeks. To reach target blood
      pressure, it is likely that a large proportion of patients will require
      combination therapy with more than one agent. The main benefits of
      antihypertensive therapy are due to lowering of blood pressure per se. There is
      also evidence that specific drug classes may differ in some effect or in special
      groups of patients. The choice of drugs will be influenced by many factors,
      including previous experience of the patient with antihypertensive agents, cost
      of drugs, risk profile, presence or absence of target organ damage, clinical
      cardiovascular or renal disease or diabetes, patient's preference.

PMID- 16810474
TI  - [Tako-tsubo cardiomyopathy. Incidence in patients with acute coronary syndrome].
AB  - BACKGROUND AND METHODS: In 2005, an emergency coronary angiography was performed
      at the authors' clinic in 215 patients (148 men, 67 women) with troponin-positive
      acute coronary syndrome. RESULTS: In five of these patients (exclusively women,
      mean age [+/- SD] 61 +/- 12 years), tako-tsubo cardiomyopathy was identified.
      This represents a frequency of 2.3% (5/215 patients) of all investigated patients
      and of 7.5% (5/67 patients) within the group of women. In these patients,
      levocardiography revealed severe left ventricular dysfunction with apical wall
      motion abnormality known as "apical ballooning". At angiography, a significant
      coronary artery disease could be excluded. Chest pain was present in all
      patients, combined with ST segment elevation in one (20%) and T-wave inversion in
      four (80%). Elevated cardiac markers were found in all cases. All patients
      experienced psychologically stressful circumstances preceding the onset of
      symptoms. The patients all survived, showing normalized ejection fraction and
      rapid restoration of previous cardiovascular function within a mean (+/- SD) of
      15 +/- 11 days. CONCLUSION: Tako-tsubo cardiomyopathy is a distinctive form of
      regional left ventricular dysfunction triggered by psychologically stressful
      events, which has a favorable clinical outcome. With a remarkable frequency of
      7.5% especially in women, tako-tsubo cardiomyopathy should be included in the
      differential diagnosis of acute myocardial infarction.

PMID- 16810475
TI  - [Psychosocial co-symptoms in primary care patients with heart failure].
AB  - BACKGROUND AND PURPOSE: Psychosocial distress is a common phenomenon in patients
      with heart failure (HF). The aim of this study was to analyze psychosocial co
      symptoms and their relationship with clinical and sociodemographic factors.
      METHODS: In 363 primary care patients with HF, anxiety, depression and negative
      affectivity (HADS, DS-14), disease coping (FKV) and social support (F-SozU) were
      measured by validated questionnaires. Severity of HF (according to NYHA
      classification and Goldman's Specific Activity Scale) and sociodemographic
      characteristics were documented by self-report instruments. RESULTS: Increased
      anxiety and/or depression was found in 29.2% of patients. Anxiety and depression
      scores were significantly higher than in the German general population (p <
      0.005). They were furthermore associated with NYHA and Goldman class (anxiety: p
      = 0.001; depression: p = 0.001). One third of the sample showed the type D
      personality pattern, which has been associated with increased mortality in
      cardiac patients. While HF severity correlated positively with psychological
      distress, patients living together with other persons had lower HF class than
      those living alone. Using regression analysis, sociodemographic and psychological
      variables predicted perceived severity of HF in 20.3% if measured by Goldman's
      scale (significant for sex, age, depressive symptoms and disease coping), and in
      18.6% if measured by NYHA (significant for anxiety). DISCUSSION: Severity of HF
      symptoms and psychosocial factors are interrelated. Self-reported severity of HF
      is substantially influenced by demographic and psychological variables. In this,
      it is not relevant if severity is measured by a nonvalidated (NYHA) or a
      validated instrument (Goldman). CONCLUSION: In primary care patients with HF,
      psychosocial co-symptoms are frequent and interfere with perceived severity of
      disease. Psychological distress should be considered important in diagnostics and
      treatment, especially in patients living alone.

PMID- 16810476
TI  - [Diagnosis and treatment of inflammatory heart diseases: role of endomyocardial
      biopsy].

PMID- 16810477
TI  - Acute massive pulmonary embolism detected with angiography and intravascular
      ultrasound treated by pulmonary embolectomy. The hybrid concept.

PMID- 16810480
TI  - [Could balneology and medical climatology have more than historic importance in
      the therapy of chronic diseases?].

PMID- 16810481
TI  - [Can the effects of radon therapy be scientifically substantiated?].

PMID- 16810482
TI  - [Adult autoimmune thrombocytopenia: diagnosis and treatment].
AB  - The incidence of AITP is 20-30/million/year. The diagnosis is based on the
      finding of an isolated thrombocytopenia without other blood abnormalities and
      absence of a palpable spleen. Additional tests such as bone marrow examination,
      determination of platelet antibodies and of thrombopoetin are required only in
      special cases. The usual first line therapy in patients with bleeding tendency
      and a low platelet count is prednisolone at a dose of 1 mg/kg/day. Patients who
      have platelet counts of less than 20,000/microl 3-6 months after steroid therapy
      are candidates for splenectomy, in particular if more than 0.1 mg/kg/day
      prednisolone is required to keep the patient free of bleedings. Laparoscopic
      splenectomy has a low mortality (0.2%) and morbidity (10%). The risk of post
      splenectomy overwhelming pneumococcal septicaemia can be minimized by
      preoperative vaccination. Older patients, who have low platelet counts after
      splenectomy, have a high bleeding risk. The most effective treatment options for
      these patients are cyclophosphamide, azathioprine and rituximab, but the choice
      of treatment should be carefully considered, since the risk of adverse effects
      may be greater than the risk of fatal bleeding.

PMID- 16810483
TI  - Solitary pulmonary hematoma--unusual complication of thrombolytic treatment.

PMID- 16810484
TI  - Effect of combined spa-exercise therapy on circulating TGF-beta1 levels in
      patients with ankylosing spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the
      axial joints with no satisfactory therapy. Reduction of joint pain has been
      reported after a course of therapy at a spa, Gasteiner Heilstollen, in Badgastein
      in Austria. The mechanism underlying this beneficial effect is not clearly
      understood and objective evidence for the biological response to therapy is
      lacking. The aim of this study was to find evidence for a biological response to
      speleotherapy in patients with AS and to study the involvement of the
      antiinflammatory cytokine TGF-beta1 in this response. PATIENTS AND METHODS: 83
      patients with AS were treated in Badgastein for 3-4 weeks. Therapy included
      active exercises, hyperthermia and exposure to low doses of radon in a former
      mine. Response to therapy was assessed from measurement of morning pain and
      immunoassay of serum levels of TGF-beta1 before and after therapy. Ten AS
      patients who received conventional therapy and 10 patients with low back pain
      (LBP) served as controls. RESULTS: A significant increase in TGF-beta1 (total and
      active) was found in AS patients after spa therapy. Mean concentration of total
      TGF-beta1 increased from 28,715 pg/ml to 43,136 pg/ml, (P<0.01) and active TGF
      beta1 increased from 77 pg/ml to 1096 pg/ml (P<0.001). When the AS patients were
      divided into two groups according to pain reduction, group 1 (decrease in morning
      pain, responders: n=46) exhibited a 17-fold increase of active TGF-beta1 levels
      (96 pg/ml to 1654 pg/ml, P<0.0001) whereas group 2 (no change or an increase in
      morning pain: nonresponders: n=37), showed only 7-fold increase (53 pg/ml to 402
      pg/ml, P<0.01). There was a moderate increase in active TGF-beta1 from 31 pg/ml
      to 42 pg/ml (P<0.05) in patients with LBP and no significant change was observed
      in the patients treated with conventional therapy. CONCLUSION: These results
      demonstrate a significant increase in circulating TGF-beta1 in patients with AS
      after the combined spa-exercise therapy in Badgastein. The results also provide
      evidence for a biological response to speleotherapy and suggest that TGF-beta,
      through its antiinflammatory function, may play a role in this response.

PMID- 16810485
TI  - Uveitis and neurologic diseases: an often overlooked relationship.
AB  - AIM: Eye and brain are linked by development, and immune privileges preserve the
      integrity of these delicate organs thereby preventing irreversible defects in
      function. Manifestation of inflammatory or immune-mediated diseases in both
      systems seems perspicuous, yet during check-up of patients with uveitis they are
      rarely considered. In this study we aimed to determine the frequency of
      neurologic diseases in our uveitis patients and to describe the characteristics
      of ophthalmologic findings. METHODS: We analyzed the database of 1973 consecutive
      patients seen between 2000 and 2004 at the uveitis clinic at the hospital of the
      Medical University of Vienna. All cases of uveitis associated with neurologic co
      manifestations of immune-mediated diseases were selected. RESULTS: Of 1973
      patients with uveitis, 52 (2.6%) had neurologic diseases that were considered to
      be related to the eye inflammation. The most frequent entities were multiple
      sclerosis, Vogt-Koyanagi-Harada's disease, neurobehcet, central nervous system
      lymphoma, neurosyphilis and neurosarcoidosis. Uveitis was only rarely seen with
      infectious meningoencephalitis (neuroborreliosis, mumps, measles), Takayasu
      arteritis, Guillain-Barre syndrome or orbital pseudotumor. CONCLUSIONS: Several
      diseases can cause both ocular and/or central nervous system inflammation. This
      should prompt ophthalmologists and neurologists in the presence of one to rule
      out the other. In uveitis patients without evident neurological symptoms,
      specific ocular pathologies can help the treating ophthalmologist to tailor the
      work-up, whereas neurologists should always screen their patients, even when they
      are asymptomatic for ocular disease. Early diagnosis in both cases can help to
      initiate adequate treatment, thereby modulating the course of the disease and
      preventing complications.

PMID- 16810486
TI  - Active hospital-based surveillance of rotavirus diarrhea in Austrian children,
      period 1997 to 2003.
AB  - BACKGROUND: Rotavirus is the most common pathogen causing severe dehydrating
      diarrhea in infants and young children worldwide. Any decision on implementation
      of rotavirus vaccination will be strongly influenced by the expected reduction in
      severe and therefore costly outcomes associated with rotavirus infection. The aim
      of this study was to provide data on hospitalization of young children with
      rotavirus infection in Austria. METHODS: The data were derived from active
      hospital-based sentinel surveillance for rotavirus during the period 1997 to
      2003. RESULTS: During this period 25,600 children<15 years of age were
      hospitalized with acute laboratory-confirmed rotavirus gastroenteritis, the
      infection showing seasonal peaks between February and March. In 5 % of the cases
      first symptoms of diarrhea occurred at a minimum of 48 hours after hospital
      admission, indicating healthcare-associated origin of infection. The mean annual
      incidence of hospitalization per 100,000 population for the age group<5 years was
      766 and for those<2 years 1742, the latter meaning that 1 in 60 Austrian children
      up to 2 years of age required hospitalization. An average peak incidence was
      observed between 8 and 14 months of age, with an average of 68% of the reported
      cases occurring in children aged<or=24 months. The mean length of hospital stay
      was 4.7 days, resulting in 17,200 rotavirus-associated hospital days per year.
      CONCLUSIONS: The observed incidence of hospitalization due to rotavirus in
      Austria is slightly higher than that reported in other industrialized countries.
      Our results reflect the considerable number of rotavirus-associated pediatric
      hospital in-patient days per year and the substantial annual direct costs of
      hospital care.

PMID- 16810488
TI  - Prolonged psychosis after Amanita muscaria ingestion.
AB  - Amanita muscaria has a bright red or orange cap covered with small white plaques.
      It contains the isoxazole derivatives ibotenic acid, muscimol and muscazone and
      other toxins such as muscarine. The duration of clinical manifestations after A.
      muscaria ingestion does not usually exceed 24 hours; we report on a 5-day
      paranoid psychosis after A. muscaria ingestion. A 48-year-old man, with no
      previous medical history, gathered and ate mushrooms he presumed to be A.
      caesarea. Half an hour later he started to vomit and fell asleep. He was found
      comatose having a seizure-like episode. On admission four hours after ingestion
      he was comatose, but the remaining physical and neurological examinations were
      unremarkable. Creatine kinase was 8.33 microkat/l. Other laboratory results and
      brain CT scan were normal. Toxicology analysis did not find any drugs in his
      blood or urine. The mycologist identified A. muscaria among the remaining
      mushrooms. The patient was given activated charcoal. Ten hours after ingestion,
      he awoke and was completely orientated; 18 hours after ingestion his condition
      deteriorated again and he became confused and uncooperative. Afterwards paranoid
      psychosis with visual and auditory hallucinations appeared and persisted for five
      days. On the sixth day all symptoms of psychosis gradually disappeared. One year
      later he is not undergoing any therapy and has no symptoms of psychiatric
      disease. We conclude that paranoid psychosis with visual and auditory
      hallucinations can appear 18 hours after ingestion of A. muscaria and can last
      for up to five days.

PMID- 16810487
TI  - The role of preoperative lymphoscintigraphy in surgery planning for sentinel
      lymph node biopsy in malignant melanoma.
AB  - AIM: To evaluate four years of preoperative lymphoscintigraphy experience and the
      accuracy of sentinel lymph node biopsy in our institution in melanoma patients
      with various tumor thicknesses. An additional aim was to evaluate the recurrence
      rate related to pathohistological findings. METHODS AND PATIENTS: During the
      period from February 2002 to November 2005, 201 patients underwent sentinel node
      biopsy. Lymphoscintigraphy for identification of sentinel nodes was performed
      four to six hours prior to operation of the patient. Sentinel lymph node biopsy
      using an intraoperative hand-held gamma probe was performed in all patients,
      together with wide local excision of biopsy wound or primary lesion (N=56).
      Immediate complete basin dissection was performed in patients with sentinel node
      metastases. In four patients delayed complete lymph node dissection was performed
      after definitive histopathologic examination of sentinel nodes. The accuracy of
      sentinel node biopsy was determined by comparing the intraoperative rates of
      sentinel node identification and the subsequent development of nodal metastases
      in regional nodal basins in patients with tumor-negative sentinel nodes and in
      those with tumorpositive sentinel nodes. RESULTS: Using preoperative
      lymphoscintigraphy, we identified sentinel nodes in all but one of the 201
      patients (99.0%), and in 248 nodal basins (1.2/patient) we observed 372 sentinel
      nodes (1.52 sentinels/basin; 1.8 sentinels/patient). The highest number of
      sentinel nodes was noticed in the groin of patients with melanoma on the lower
      extremities (1.5/patient), followed by the axilla (1.3/patient). Anomalous
      lymphatic drainage patterns were observed in 15.0% of all patients. The
      identification rate of sentinel nodes was 99.0% overall: 100% for the groin
      basins, and 98.0% for the axilla and head and neck basin. Forty-two patients
      (20.8%) had tumor-positive sentinel nodes. Ten patients (5.0%) had local or
      distant recurrences during a median follow-up of 23.1 months (range 2-46). The
      rate of false-negative lymphatic mapping and sentinel node biopsy as measured by
      nodal recurrence in patients with tumor-negative sentinel nodes was 1.3%. During
      the follow-up period, three of 201 patients died from other diseases and three
      patients died as the result of melanoma metastases, with a median follow-up of
      13.5 months (range 12-22). CONCLUSION: Preoperative lymphoscintigraphy is a
      sensitive, inexpensive and essential method for the identification of drainage
      basins, determination of the number and position of sentinel nodes and their
      location outside the usual nodal basins. Scintigraphic findings may lead to
      changes in surgical management due to the unpredictability of lymphatic drainage.
      The low incidence of regional disease recurrence in patients with tumor-negative
      sentinel nodes supports the use of preoperative lymphoscintigraphy and sentinel
      node biopsy as a safe and accurate procedure for staging the regional nodal basin
      in patients with malignant melanoma.

PMID- 16810489
TI  - Bridging to transplantation in acute liver failure in a 7-month-old infant.
AB  - BACKGROUND: Acute liver failure (ALF) in children is a rare but often fatal
      event. At present, liver transplantation is the only successful therapy in most
      cases. In the face of deteriorating hepatic encephalopathy in these children,
      some bridging therapy using artificial detoxification can be necessary to enable
      successful transplantation. In adults, albumin dialysis using the molecular
      absorbent recycling system (MARS) has been described as effective for bridging to
      liver transplantation. CASE REPORT: A previously healthy 7-month-old infant was
      admitted with ALF due to autoimmune hepatitis. King's College criteria for
      children with ALF indicated the need for transplantation (bilirubin 13.7 mg/dl,
      leukocytes 18,980/mm3, INR 5.83, age<2 years). Despite moderate hyperammonemia
      (75 microm/l) along with the development of pneumonia, the child deteriorated
      hemodynamically and neurologically, showing grade III encephalopathy proven by
      EEG. Albumin dialysis using MARS was used to bridge 36 hours to successful living
      donor split-liver transplantation, and resulted in improvements in EEG, plasma
      levels of amino acids and hemodynamics. Twenty-four months after transplantation
      the child shows normal liver function and normal neuropsychological development.
      The explanted liver showed 80 % tissue destruction from autoimmune hepatitis.
      CONCLUSION: Albumin dialysis as described can be used successfully in infants < 1
      year old for bridging to liver transplantation in cases of acute hepatic failure
      with deteriorating encephalopathy.

PMID- 16810490
TI  - [Recurring obstructive bronchitis and asthmatic bronchitis in preschool aged
      children].

PMID- 16810492
TI  - Anatomical hemispherectomy.
AB  - INTRODUCTION: Anatomical hemispherectomy is frequently employed in the surgical
      management of pediatric patients with medically refractory epilepsy. MATERIALS
      AND METHODS: In this chapter, we review the historical evolution of this surgical
      procedure, outline the indications and the criteria for selecting surgical
      candidates and describe the important pre-operative evaluation of the surgical
      candidates. DISCUSSION: We provide a detailed description of our surgical
      technique, anesthesiological considerations, and post-operative care plan.
      Ultimately we analyze the most common complications associated with this
      procedure. CONCLUSION: Anatomical hemispherectomy performed in carefully selected
      pediatric patients with medically intractable epilepsy can be a safe and
      efficacious surgical procedure.

PMID- 16810493
TI  - [Procedures of temporary wall closure in abdominal trauma and sepsis].
AB  - Temporary abdominal closure methods differ mainly between vacuum-assisted and
      conventional approaches. Each method has its indications. Vacuum-assisted methods
      seem to be superior especially for trauma indications--in terms of lethality, the
      possibility of secondary closure during primary hospital stay, and frequency of
      enterocutaneous fistulas. Skin-only closure might be used as a short-term
      application (e.g. when damage control closure is needed), and the Bogota bag silo
      gives space to protruding bowels in pending or manifest abdominal compartment
      syndrome. Temporary fascial mesh closure enables repetitive laparotomies through
      the mesh, thus sparing the fascia. For that reason it is to be preferred,
      especially for its good practicability in clinical situations and on mission
      abroad.

PMID- 16810495
TI  - Primate errors in transitive 'inference': a two-tier learning model.
AB  - Transitive performance (TP) is a learning-based behaviour exhibited by a wide
      range of species, where if a subject has been taught to prefer A when presented
      with the pair AB but to prefer B when presented with the pair BC, then the
      subject will also prefer A when presented with the novel pair AC. Most
      explanations of TP assume that subjects recognize and learn an underlying
      sequence from observing the training pairs. However, data from squirrel monkeys
      (Saimiri sciureus) and young children contradict this, showing that when three
      different items (a triad) are drawn from the sequence, subjects' performance
      degrades systematically (McGonigle and Chalmers, Nature 267:694-696, 1977;
      Chalmers and McGonigle, Journal of Experimental Child Psychology 37:355-377,
      1984; Harris and McGonigle, The Quarterly Journal of Experimental Psychology
      47B:319-348, 1994). We present here the two-tier model, the first learning model
      of TP which accounts for this systematic performance degradation. Our model
      assumes primate TP is based on a general-purpose task learning system rather than
      a special-purpose sequence-learning system. It supports the hypothesis of Heckers
      et al. (Hippocampus 14:153-162, 2004) that TP is an expression of two separate
      general learning elements: one for associating actions and contexts, another for
      prioritising associations when more than one context is present. The two-tier
      model also provides explanations for why phased training is important for helping
      subjects learn the initial training pairs and why some subjects fail to do so. It
      also supports the Harris and McGonigle (The Quarterly Journal of Experimental
      Psychology 47B:319-348, 1994) explanation of why, once the training pairs have
      been acquired, subjects perform transitive choice automatically on two-item
      diads, but not when exposed to triads from the same sequence.

PMID- 16810498
TI  - Antenatal MR diagnosis of urinary hydrometrocolpos due to urogenital sinus.
AB  - Hydrometrocolpos is cystic dilatation of the vagina and uterus due to congenital
      vaginal obstruction. It may be secretory or urinary in character and manifests in
      the neonatal period with abdominal distension. Urinary hydrometrocolpos occurs in
      patients with urogenital sinus or cloacal anomaly. A rare case of antenatal MR
      diagnosis of urinary hydrometrocolpos due to urogenital sinus is presented.

PMID- 16810496
TI  - Insights in the glycosylation steps during biosynthesis of the antitumor
      anthracycline cosmomycin: characterization of two glycosyltransferase genes.
AB  - Glycosylation pattern in cosmomycins is a distinctive feature among
      anthracyclines. These antitumor compounds possess two trisaccharide chains
      attached at C-7 and C-10, each of them with structural variability, mainly at the
      distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from
      Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis.
      Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated
      with the generation of five new derivatives. Structural elucidation of these
      compounds showed altered glycosylation patterns indicating the capability of both
      glycosyltransferases of transferring deoxysugars to both sides of the aglycone
      and the flexibility of CosK with respect to the deoxysugar donor. A model is
      proposed for the glycosylation steps during cosmomycins biosynthesis.

PMID- 16810499
TI  - [Influence of neurological diseases on partnership and sexuality. Particularly in
      view of multiple sclerosis and Parkinson's disease].
AB  - A great number of neurological diseases exert a direct impact on sexuality, due
      to lesions in the central and peripheral nervous system and due to different
      neurological symptoms and their treatment (for example medication). The
      psychosocial basic needs for acceptance, intimacy, and security, which can be
      best fulfilled by sexual communication, attain essential importance in the
      situation of disease-induced helplessness. This implies that not only the
      experience of sexual pleasure and the functioning of reproduction can be
      influenced, but the partnership, too. A holistic treatment approach always
      requires the consideration of partnership aspects.

PMID- 16810500
TI  - Lysophosphatidylcholine suppresses apoptotic cell death by inducing
      cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human
      cholangiocytes.
AB  - PURPOSE: The high incidence of biliary tract carcinoma in patients with anomalous
      pancreaticobiliary ductal junction (APBDJ) implicates that a compositional
      alteration in bile may contribute to the genesis of this cancer.
      Lysophosphatidylcholine (LPC) is generated in the bile of these patients. Given
      the role of cyclooxygenase-2 (COX-2) in biliary tract carcinogenesis, we
      postulated that LPC induces COX-2 in cholangiocytes. METHODS: The effect of LPC
      on COX-2 expression in cholangiocytes was evaluated by immunoblot analysis, real
      time PCR and reporter gene assay. Apoptosis was induced by TRAIL treatment, and
      quantified using DAPI staining. RESULTS: Lysophosphatidylcholine increased COX-2
      protein expression in cholangiocytes in a concentration- and time-dependent
      manner. LPC-induced Raf-1 activation was responsible for this COX-2 induction.
      Accordingly, LPC increased COX-2 mRNA levels in a Raf-1 dependent manner by
      stabilizing COX-2 mRNA. Finally, LPC attenuated TRAIL-mediated apoptosis through
      a COX-2/PgE2 dependent mechanism. CONCLUSIONS: Collectively, these results
      implicate that LPC inhibits cholangiocyte apoptosis by inducing COX-2 expression
      via a Raf-1 dependent mechanism. This anti-apoptotic signaling may participate in
      biliary tract carcinogenesis in APBDJ patients, and therefore, its interruption
      may be a viable chemopreventative strategy.

PMID- 16810501
TI  - Epigenetic silencing of the putative tumor suppressor gene testisin in testicular
      germ cell tumors.
AB  - PURPOSE: Testisin, a serine protease abundantly expressed only in normal testes,
      is thought to be a tumor suppressor gene silenced by aberrant methylation in
      testicular germ cell tumors (TGCT). This study aimed at identifying the CpG sites
      relevant for testisin gene silencing when methylated and evaluating the potential
      of aberrant methylation as a biomarker in TGCT. METHODS: Bisulfite sequencing and
      subsequent real-time RT-PCR were carried out in germ cell tumor cell lines and a
      cervical carcinoma cell line to reveal CpG sites implicated in testisin gene
      silencing. The normalized index of methylation (NIM) and the relative gene
      expression (RGE) were calculated in 33 TGCT and 19 normal testicular tissue
      samples by quantitative methylation-specific PCR (QMSP) and real-time RT-PCR.
      RESULTS: CpG sites in the 5'untranslated region proved to be relevant for
      testisin gene silencing when methylated. Targeting these CpG sites by QMSP, we
      demonstrated that the median NIM was 8.6 times higher in the TGCT group than in
      normal testicular samples. This was associated with a median 23.6 times lower RGE
      in the TGCT probes. Non-seminomas had a significantly higher NIM than seminomas,
      but RGE was downregulated to comparable levels in both subgroups. QMSP was highly
      sensitive and distinguished TGCT from normal samples with excellent specificity.
      CONCLUSIONS: Our results demonstrate for the first time that aberrant methylation
      of specific CpG sites near the transcription initiation site is an important
      factor in testisin gene silencing in TGCT.

PMID- 16810502
TI  - Expression and prognostic role of RhoA GTPases in hepatocellular carcinoma.
AB  - The Rho sub-family of proteins is involved in regulating the organization of the
      cytoskeleton and in cell motility. Our aim is to clarify the clinical
      significance of Rho protein in hepatocellular carcinomas (HCC) and to determine
      the relationship between the level of expression and patient outcome following
      hepatectomy. The expression of RhoA protein in HCC and corresponding non-tumor
      tissues of 26 patients who underwent surgical resection was analyzed by
      immunoblotting. The expression level of each case was calculated as tumor/non
      tumor (T/N) ratios. High expression (T/N> or =1) of RhoA protein in HCC compared
      to the paired non-tumor tissues was recognized in 18 patients (69.2%) of 26
      samples. The activity of RhoA is also increased in HCC with high expression of
      RhoA. The high expression of RhoA protein did not correlate with various clinical
      parameters. However, the disease-free survival rates of the RhoA-high expression
      group (T/N> or =1) were significantly lower than those of the RhoA-low expression
      group (T/N<1) (P<0.05). The high expression of RhoA protein in HCC plays an
      important role in intrahepatic recurrence of patients who underwent a hepatectomy
      for HCC, and RhoA is a useful marker for predicting early recurrence in an early
      stage HCC.

PMID- 16810503
TI  - Leaf mechanical properties modulate feeding movements and ingestive success of
      the pond snail, Lymnaea stagnalis.
AB  - We examined the mechanical properties of Butterhead and Iceberg lettuce leaves,
      and the rate at which they were eaten by the pond snail Lymnaea stagnalis. The
      outer part of Butterhead leaves were less robust than either the inner Butterhead
      or outer Iceberg leaves (Young's modulus 2.8, 5.2, 7.7 MPa respectively; ultimate
      tensile stress 0.18, 0.34 0.51 MPa) which were also thicker. Snails ingested
      inner Butterhead and Iceberg strips more slowly (36 and 32%) than outer
      Butterhead. This was not due to differences in latency to first bite or biting
      rate. Rather, the drop was due to a decrease in the proportion of successful
      bites (inner Butterhead 84%; Iceberg 86%), to a shorter length ingested per bite
      (inner Butterhead 55%; Iceberg 45%) and to increased handling time (inner
      Butterhead 30%). We conclude that sensory input from the mechanically more robust
      lettuce slows the buccal central pattern generator.

PMID- 16810504
TI  - Dissection of the nuclear genome of barley by chromosome flow sorting.
AB  - Isolation of mitotic chromosomes using flow cytometry is an attractive way to
      dissect nuclear genomes into their individual chromosomal components or portions
      of them. This approach is especially useful in plants with complex genomes, where
      it offers a targeted and hence economical approach to genome analysis and gene
      cloning. In several plant species, DNA of flow-sorted chromosomes has been used
      for isolation of molecular markers from specific genome regions, for physical
      mapping using polymerase chain reaction (PCR) and fluorescence in situ
      hybridization (FISH), for integration of genetic and physical maps and for
      construction of chromosome-specific DNA libraries, including those cloned in
      bacterial artificial chromosome vectors. Until now, chromosome analysis and
      sorting using flow cytometry (flow cytogenetics) has found little application in
      barley (2n = 14, 1C approximately 5,100 Mbp) because of the impossibility of
      discriminating and sorting individual chromosomes, except for the smallest
      chromosome 1H and some translocation chromosomes with DNA content significantly
      different from the remaining chromosomes. In this work, we demonstrate that wheat
      barley ditelosomic addition lines can be used to sort any arm of barley
      chromosomes 2H-7H. Thus, the barley genome can be dissected into fractions
      representing only about 6-12% of the total genome. This advance makes the flow
      cytogenetics an attractive tool, which may greatly facilitate genome analysis and
      gene cloning in barley.

PMID- 16810505
TI  - Evaluation of antipsychotic drugs as inhibitors of multidrug resistance
      transporter P-glycoprotein.
AB  - RATIONALE: The multidrug resistance transporter, P-glycoprotein (P-gp), is
      involved in efflux transport of several antipsychotics in the blood-brain barrier
      (BBB). OBJECTIVES: In the present study, we evaluated the inhibitory effect of
      the antipsychotics, i.e., risperidone, olanzapine, quetiapine, clozapine,
      haloperidol, chlorpromazine, a major metabolite of risperidone, 9-OH-risperidone,
      and a positive control inhibitor, PSC833, on the cellular uptake of a prototypic
      substrate of P-gp, rhodamine (Rhd) 123, in LLC-PK1 and L-MDR1 cells. MATERIALS
      AND METHODS: After incubation of the antipsychotics (1-100 microM) and the
      positive (10 microM PSC833) or negative (1% dimethyl sulfoxide) controls with 5
      microM Rhd 123 for 1 h, the effects of the antipsychotics on the intracellular
      accumulation of Rhd 123 were examined using a flow cytometric method. RESULTS:
      All the antipsychotics showed various degrees of inhibitory effects on P-gp
      activity. The rank order of the concentration of inhibitor to cause 50% of the
      maximal increment of intracellular Rhd 123 fluorescence (EC(50)) was: PSC833 (0.5
      microM) < olanzapine (3.9 microM) < chlorpromazine (5.8 microM) < risperidone
      (6.6 microM) < haloperidol (9.1 microM) < quetiapine (9.8 microM) < 9-OH
      risperidone (12.5 microM) < clozapine (30 microM). Considering that the
      antipsychotics' plasma concentrations are generally lower than 1 microM, the
      present results suggest that olanzapine and risperidone are the only agents that
      may inhibit P-gp activity in the BBB. However, most of the antipsychotics are
      extensively accumulated in tissues. In addition, when given orally, the drug
      concentrations in the gastrointestinal tract are likely to be high. CONCLUSIONS:
      Pharmacokinetic interactions due to inhibition of P-gp activity by the
      antipsychotics appear possible and warrant further investigation.

PMID- 16810506
TI  - The neurocognitive effects of aripiprazole: an open-label comparison with
      olanzapine.
AB  - RATIONALE: Cognitive deficits are a core feature of schizophrenia. As a target of
      intervention, improvements in cognition may lead to improvements in functional
      outcome. OBJECTIVES: The present paper is the first report, to our knowledge, on
      the neurocognitive effects of aripiprazole. Unlike other second-generation
      antipsychotics, aripiprazole is a D(2) and D(3) receptor partial agonist. It is
      unknown what effects this unusual pharmacological profile may yield on
      neurocognition. MATERIALS AND METHODS: The present open-label study included data
      on 169 patients with schizophrenia or schizoaffective disorder who were randomly
      treated with aripiprazole or olanzapine. Subjects received a neurocognitive
      battery at baseline, week 8, and 26. RESULTS: The aripiprazole group had a
      significantly greater dropout rate than the olanzapine group. Neurocognitive data
      were reduced through a principal components analysis that yielded a three-factor
      solution. The factors were general cognitive functioning, executive functioning,
      and verbal learning. For general cognitive functioning, both groups improved from
      baseline and the effects were relatively stable over the 26-week protocol. There
      were no differential treatment effects. For executive functioning, neither group
      improved significantly from baseline. For verbal learning, the aripiprazole group
      improved significantly from baseline to the 8th and 26th week of assessment, and
      there was a between-group effect favoring aripiprazole over olanzapine that was
      largely attributable to the differences in performance within the 8th week.
      Separate analyses were conducted for a measure of sustained attention (Continuous
      Performance Test-Identical Pairs). There were no differential treatment effects
      on this measure. CONCLUSIONS: The findings from this open-label study suggest
      that the neurocognitive effects of aripiprazole are at least as good as those of
      olanzapine.

PMID- 16810508
TI  - Comment on the publication "Vehicle of triamcinolone acetonide is associated with
      retinal toxicity and transient increase in lens density" by W. Kai et al.

PMID- 16810509
TI  - Living unrelated-commercial-kidney transplantation: when there is no chance to
      survive.
AB  - Transplantation is the best treatment of end-stage renal disease (ESRD); however,
      organ shortage is a reality. Deceased donor organ donation is inadequate; hence,
      the number of patients on the waiting lists is increasing progressively. Since
      many ESRD patients do not have living genetically related donors, living
      unrelated transplantation is considered. These transplantations offer excellent
      graft and patient survival rates if practiced in conventional situations, while
      the results are not so favorable or even poor in unconventional transplantations,
      which mostly take place in developing countries. Ethical aspects of living
      unrelated transplantation are more complicated than the medical side due to
      concern of commercialization. Making payment to the donors has been considered
      strictly as nonethical by many authors, while some others suggest reopening
      previous debates for kidney sales. The latter claim that if exploitation of
      donors is avoided, the reward (or payment) to the donor can be morally justified.
      Apart from these controversies, it is uniformly accepted that commercial
      transplantation is certainly unethical when brokers are involved or the aim is
      just profit for transplant physicians, because the main reason in favor of organ
      sales is improving the quality of life of the patients and the donors, not the
      brokers or the physicians. All these theoretical ethical arguments in the Western
      countries turn out to become vital concerns in developing countries, because
      transplantation is the cheapest renal replacement therapy. Recently, it has been
      suggested that organ shortage problems can partly be solved by establishing
      controlled donor compensation programs in these countries, which may also prevent
      exploitation of the donors. However, it is impossible to suggest a uniform
      solution for all countries because of deep differences in economical status as
      well as social and cultural values. Thus, every country should build its own
      ethical standards for commercial transplantation.

PMID- 16810510
TI  - Commercial living non-related organ transplantation: a viewpoint from a developed
      country.
AB  - In developed countries, the use of living unrelated donors is restricted to
      purely altruistic donors who have a close and emotional relationship with the
      recipients. By law, commercial transplantation is illegal. Increasing shortness
      of donors, the excellent results of kidney transplants from spousal and living
      unrelated donors as well as the very low risk for the donor has been used as an
      argument for paid organ donation. Arguments in favour are the relief of donor
      organ shortage, short waiting times for renal transplantation, economic benefits
      for the donor as well as the economic benefits for society by reducing the costs
      of dialysis by more transplants. Major arguments against are exploitation of the
      donor, coercion, and a growing black market. Despite the fact that different
      societies have different norms or reproaches that we are failing our patients and
      accept the death of thousands, kidney trade has created an environment of
      corruption and commercialisation, which brings even the cadaver transplant
      program into disrepute. However, denying the existence of paid organ donation
      does not contribute to solve the problem. A public discussion about consequences
      of changing ethics and human rights, rather than pragmatic solutions, is needed.

PMID- 16810511
TI  - Low protein Z levels in children with nephrotic syndrome.
AB  - Acquired deficiency of anticoagulant proteins, due to loss in the urine, has been
      proposed as one of the major thrombogenic alterations in nephrotic syndrome (NS).
      Protein Z (PZ) is a single-chain vitamin K-dependent glycoprotein. Low PZ levels
      are reported to be a risk factor for thrombosis. The aim of this study was to
      investigate protein Z and other natural anticoagulant levels in children with NS.
      Thirty children aged between 1.5 and 12 years with NS (Groups I and II) and 19
      age-and-sex-matched healthy controls (Group III) were enrolled into the study.
      Patients were divided into two groups: Group I (proteinuria >40 mg/m2/hr) and
      Group II (patients in remission). Plasma PZ levels in Group I were significantly
      lower than Group II (p=0.009) and group III (p=0.018). Plasma levels of AT III
      for Group I were significantly lower than for Groups II and III (p=0.009,
      p=0.005, respectively). Protein C levels in Group I were higher than in Group II
      and Group III (p=0.002, p=0.000, respectively). Protein Z levels positively
      correlated with serum total protein and albumin levels (p=0.003, p=0.003,
      respectively) and negatively with the degree of proteinuria (p=0.000). Protein Z
      levels were positively correlated with AT III (r=0.037, p=0.04). Along with the
      other coagulation abnormalities, decreased protein Z may contribute to increased
      risk of thromboembolic complications in children with NS. The negative
      correlation between proteinuria and PZ level suggests the possibility of renal PZ
      loss. Further studies are needed to investigate the mechanism and role of
      decreased PZ in NS.

PMID- 16810512
TI  - Urine proteomic profiling of pediatric nephrotic syndrome.
AB  - The prognosis of pediatric nephrotic syndrome (NS) correlates with the
      responsiveness to glucocorticoid therapy. Steroid-resistant NS (SRNS) patients
      progress to end-stage renal disease, while steroid-sensitive NS (SSNS) and
      steroid-dependent (SDNS) patients do not. We have performed proteomic profiling
      of urine samples from a cross section of pediatric and adolescent subjects with
      SSNS, SRNS, and orthostatic proteinuria (OP) to identify urinary biomarkers of
      steroid resistance. We performed surface-enhanced laser desorption/ionization
      time of flight mass spectrometry (SELDI-TOF MS) on urine from 19 subjects with
      SSNS/SDNS in remission, 14 with SSNS/SDNS in relapse, 5 with SRNS in relapse, and
      6 with OP. Genetic algorithm search of principal component space revealed a group
      of five peaks distinguishing SRNS subjects, with mass/charge (m/z) values of
      3,917.07, 4,155.53, 6,329.68, 7,036.96, and 11,117.4. Our analyses identified the
      peak at m/z 11,117.4 with an accuracy of 95% for classifying SRNS.
      Multidimensional protein fractionation and mass spectrometric analysis of SRNS
      urine samples combined with immunodepletion identified the 11,117.4 protein as
      beta2-microglobulin (B2M). Using an unbiased protein profiling approach, we have
      validated previously reported findings of B2M as a biomarker associated with
      SRNS. Prospective studies are warranted to establish additional biomarkers that
      would be predictive of SRNS.

PMID- 16810513
TI  - The urinary activity of angiotensin-converting enzyme in preterm, full-term
      newborns, and children.
AB  - The urinary activity of the angiotensin-converting enzyme (U(ACE)) is not yet
      completely documented in human neonates. We measured the U(ACE) in 36 premature
      neonates on the 1st day and in the 1st, 2nd, 3rd, and 4th weeks of life, in 22
      full-term neonates between the 1st and 2nd days, and in 30 nursing and preschool
      children between 1 month and 6 years of age. The urinary excretion of sodium
      (U(Na)/U(Cr)) and the potassium/sodium index (U(K)/U(Na)) were analyzed in the
      neonates. U(ACE) was greater in premature than in full-term neonates and greater
      in both than in older children (p<0.001). In the premature neonates, U(ACE)
      peaked at the 2nd week, the U(Na)/U(Cr) index decreased, and the U(K)/U(Na) index
      increased between the 1st day and the 2nd week (p<0.001). The U(Na)/U(Cr) index
      on the 1st day and in the 1st and 2nd weeks was greater in premature than in full
      term neonates (p<0.001). There was no significant correlation between the U(ACE)
      and the U(Na)/U(Cr) index. In conclusion, the U(ACE) profile was shown to be age
      dependent and related to the postnatal renal development. The increase in U(ACE)
      activity may reflect the high activity of the neonatal intrarenal renin
      angiotensin system (RAS).

PMID- 16810514
TI  - First urinary tract infection in neonates, infants and young children: a
      comparative study.
AB  - In an attempt to evaluate first urinary tract infection (UTI) in neonates and
      infants, we estimated retrospectively in 296 patients (62 neonates and 234
      infants) clinical and laboratory findings, occurrence of vesicoureteral reflux
      (VUR), urinary tract abnormalities and pyelonephritis. First UTI occurred more
      often in male than female neonates, whereas male and female infants/young
      children were affected at an equal rate. The pathogens isolated in urine cultures
      of neonates and infants did not statistically significantly differ (P>0.05);
      Escherichia coli predominated. Gram-negative bacteria other than E. coli affected
      boys more often than girls (P=0.0022). Fever was the most frequent symptom.
      Neonates had lower-grade fever of shorter duration than infants (P<0.05). The
      incidence of reflux and urinary tract abnormalities did not differ between
      neonates and infants, male and female neonates and infants (P>0.05).
      Pyelonephritis affected neonates and infants at an equal rate; it was more
      prevalent among female patients (P=0.038) and patients with VUR or urinary tract
      abnormalities other than VUR (P<0.0001). Neonates with reflux were more often
      affected by Gram-negative bacteria other than E. coli than were neonates without
      reflux (P=0.0008).

PMID- 16810515
TI  - Sarcoidosis presenting with hearing loss and granulomatous interstitial nephritis
      in an adolescent.
AB  - Granulomatous interstitial nephritis is an uncommon finding in a kidney biopsy.
      The differential diagnosis is broad and includes infections, drug exposure, and
      sarcoidosis. Sarcoidosis, a systemic disorder of unknown etiology characterized
      by the presence of noncaseating granulomata in affected organs, is rare in
      children. We discuss an adolescent boy with the unusual presentation of
      granulomatous interstitial nephritis and acute deafness. Sarcoidosis should be
      considered as part of the differential diagnosis for children and adolescents
      with hearing loss and kidney disease.

PMID- 16810516
TI  - Prognosis of lupus membranous nephropathy in children.
AB  - The occurrence of membranous nephropathy in pediatric series of systemic lupus
      erythematosus has been reported only rarely, probably due to a very low
      frequency. One hundred fifty-four children who were seen in 100 French pediatric
      centers between January 2002 and April 2005 were included. Fifteen (12 girls and
      three boys) out of the 81 (18.5 %) children with renal involvement presented
      histological features of membranous nephropathy. Their ages ranged from six to 15
      years old (mean=11.3) at the age of SLE diagnosis and 8/15 children were of
      African origin. Isolated membranous nephropathy was observed in nine patients, of
      whom five patients displayed a complete recovery following immunosuppressive
      treatment. Associated proliferative lesions were observed on the first kidney
      specimen in two patients and in a further renal biopsy in four other patients,
      leading to a less favorable course of lupus nephropathy.

PMID- 16810517
TI  - Primary hyperoxaluria type 1: still challenging!
AB  - Primary hyperoxaluria type 1, the most common form of primary hyperoxaluria, is
      an autosomal recessive disorder caused by a deficiency of the liver-specific
      enzyme alanine: glyoxylate aminotransferase (AGT). This results in increased
      synthesis and subsequent urinary excretion of the metabolic end product oxalate
      and the deposition of insoluble calcium oxalate in the kidney and urinary tract.
      As glomerular filtration rate (GFR) decreases due to progressive renal
      involvement, oxalate accumulates and results in systemic oxalosis. Diagnosis is
      still often delayed. It may be established on the basis of clinical and
      sonographic findings, urinary oxalate +/- glycolate assessment, DNA analysis and,
      sometimes, direct AGT activity measurement in liver biopsy tissue. The initiation
      of conservative measures, based on hydration, citrate and/or phosphate, and
      pyridoxine, in responsive cases at an early stage to minimize oxalate crystal
      formation will help to maintain renal function in compliant subjects. Patients
      with established urolithiasis may benefit from extracorporeal shock-wave
      lithotripsy and/or JJ stent insertion. Correction of the enzyme defect by liver
      transplantation should be planned, before systemic oxalosis develops, to optimize
      outcomes and may be either sequential (biochemical benefit) or simultaneous
      (immunological benefit) liver-kidney transplantation, depending on facilities and
      access to cadaveric or living donors. Aggressive dialysis therapies are required
      to avoid progressive oxalate deposition in established end-stage renal disease
      (ESRD), and minimization of the time on dialysis will improve both the patient's
      quality of life and survival.

PMID- 16810518
TI  - Analysis of NPHS2 mutations in Turkish steroid-resistant nephrotic syndrome
      patients.
AB  - Mutations in the NPHS2 gene are a frequent cause of familial and sporadic steroid
      resistant nephrotic syndrome (SRNS). Inter-ethnic differences have also been
      suggested to affect the incidence of these mutations. The frequency and spectrum
      of podocin mutations in the Turkish population have remained largely unknown. As
      such, the aim of this study was to screen for podocin mutations in Turkish
      patients with SRNS. Thirty two patients from 30 unrelated families with SRNS were
      examined. There were seven familial cases from five different families and 25
      sporadic cases. PCR-single-strand conformation polymorphism (SSCP) analysis of
      the NPHS2 gene was followed by direct sequencing. Five different NPHS2 mutations
      were detected in four of the 30 (13.3%) families studied; five familial patients
      from three unrelated families (60%) and one sporadic case (4%) were found to
      carry podocin mutations. The detected mutations included homozygous c. 419delG,
      compound heterozygous p. [Arg238Ser] + [Pro118Leu], homozygous p. [Pro20Leu;
      Arg168His] and heterozygous p. Pro20Leu. Two siblings with compound heterozygous
      mutations had been reported previously by our group. Podocin mutations were found
      to be responsible for some of the SRNS cases in Turkey, especially when there was
      more than one affected person in the family. Our results also suggest the
      presence of a wide range of phenotypic variability between individuals with the
      same genotype.

PMID- 16810520
TI  - Organ donation in paediatric traumatic brain injury.

PMID- 16810521
TI  - Pulse oximeter in a comparative test.

PMID- 16810522
TI  - Decreased accuracy of pulse oximetry measurements during low perfusion caused by
      sepsis: Is the perfusion index of any value?
AB  - OBJECTIVE: To evaluate the effects of deteriorating perfusion caused by sepsis on
      the accuracy of pulse oximetry measurements using two more recently available
      techniques (Nellcor N-395 and Masimo Radical) and to evaluate the perfusion index
      as a marker of impaired peripheral perfusion to indicate that accuracy of pulse
      oximetry readings may be affected. DESIGN AND SETTING: Interventional cohort
      study in a university animal research facility. SUBJECTS: Thirty-seven adult
      anesthetized, ventilated rabbits. INTERVENTIONS: Pneumonia/sepsis was induced by
      tracheal instillation of Escherichia coli. MEASUREMENTS AND RESULTS: Oxygen
      saturation and perfusion index as a marker of peripheral perfusion were measured
      by pulse oximetry (SpO2) and recorded continuously for 8 h. Arterial oxygen
      saturation (SaO2) was measured every 30 min by CO oximetry, and bias (SpO2 -
      SaO2) was calculated at each time point for each device to assess time-dependent
      changes in bias. Bias increased significantly across time for both devices tested
      comparing the first with the second half of the experimental period. Bias
      measurements during the second half of the experimental time were beyond the +/
      3% error limit in 21.4% of cases with Nellcor and in 22.6% with Masimo. A lower
      perfusion index was associated with increased bias, but sensitivity, specificity,
      and positive and negative predictive values of this marker for increased bias was
      very limited. CONCLUSIONS: We conclude that accuracy of pulse oximetry
      measurements was considerably affected with both devices with progressively
      deteriorating hemodynamics in this animal model of severe sepsis. Perfusion index
      as a marker for increased risk of bias was not a useful tool.

PMID- 16810523
TI  - Platelet and soluble CD40L in meningococcal sepsis.
AB  - OBJECTIVE: To determine the influence of meningococcal sepsis on levels of
      platelet derived CD40L and on endothelial CD40 expression. DESIGN AND SETTING:
      Prospective observational study in two tertiary paediatric intensive care units.
      PATIENTS AND PARTICIPANTS: 63 children with meningococcal sepsis and 10 age
      matched controls. MEASUREMENTS AND RESULTS: (a) sCD40L ELISA of plasma from
      patients with meningococcal sepsis (n = 49) and age matched controls (n = 10).
      This demonstrated higher sCD40L levels in patients (median 0.29 ng/ml, IQR 0.2
      0.41) than controls (0.09 ng/ml, 0.08-0.12). However, there was no relationship
      between plasma sCD40L level and platelet count or disease severity. (b) Flow
      cytometry of fresh blood from patients with meningococcal sepsis (n = 11) and age
      matched controls (n = 10) for membrane bound CD40L and CD62P on circulating
      platelets. This demonstrated low levels of CD40L and CD62P in patients and
      controls. CD40L+ platelets were 3.5% (3.0-4.8) in patients and 4.9% (3.5-4.3) in
      controls. CD62P+ platelets were 10.7% (6.4-12.8) in patients and 7.9% (5.9-13.0)
      in controls. (c) Immunohistochemistry of skin biopsy specimens from six patients,
      staining for endothelial CD40 expression at sites of microthrombus formation,
      which demonstrated preserved CD40 expression in vascular endothelium at sites of
      microthrombus formation. CONCLUSIONS: The elevated sCD40L level in meningococcal
      sepsis implies release of sCD40L from platelets. However, there was no
      relationship between plasma sCD40L level and the degree of thrombocytopenia or
      disease severity. Furthermore, platelet surface bound CD40L was similar in
      controls and patients. Thus, further investigation is needed to determine whether
      platelet CD40L contributes to inflammation and thrombosis in MCS.

PMID- 16810524
TI  - Sequence stability of the T-DNA - plant junctions in tissue culture in
      Arabidopsis transgenic lines.
AB  - The stability of the inserted transgenes and particularly the junction regions of
      transgenic events is a concern of food labeling, traceability and post release
      monitoring, as these regions are used for development of event-specific DNA-based
      detection methods. During the standard agricultural breeding practices, the
      transgenic lines can be exposed to completely different conditions than those in
      the laboratory environment. Some of these conditions have the potential to affect
      the stability of the transgenic locus and the surrounding DNA. As tissue culture
      is recognized as a stressful and mutagenic factor, we have analyzed the effect of
      this process on the stability of the junction regions at nucleotide level in five
      Arabidopsis thaliana transgenic lines in comparison with the respective
      integration loci in ColO and C24 ecotypes. No indication of any kind of
      alteration at nucleotide level of the junctions was found. The relevance of the
      stability of the plant-T-DNA junction regions for application of the DNA-based
      methods in commercial transgenic plants is discussed.

PMID- 16810525
TI  - Stimulation of alkalothermophilic Aspergillus terreus xylanase by low-intensity
      laser radiation.
AB  - In this study, Aspergillus terreus was irradiated by a 7.3 mW He-Ne laser in the
      presence of crystal violet, toluidine blue O and hematoporphyrin as
      photosensitizers. Xylanases recovered from non-irradiated and irradiated fungi
      were purified and characterized. The maximum production of xylanase (42.2 U/ml)
      was obtained after 5 min of laser irradiation in the absence of the
      photosensitizer. The irradiation of the sensitized fungus diminished the
      production of xylanase. On purification using G-100, the specific activity of
      xylanase recovered from the irradiated fungus was 292 U/mg protein representing a
      37-fold purification over the crude extract compared with 95.6 U/mg protein
      representing the 12.8-fold for the enzyme recovered from the non-irradiated
      fungus. The enzyme recovered from the irradiated fungus had lower molecular
      weight as compared with that recovered from the non-irradiated one.
      Characterization of the purified enzymes revealed that the enzyme recovered from
      the irradiated fungus was more thermostable and had a wider range of optimum
      reaction temperature (60-70 degrees C) and pH (4.0-12.0), compared to the non
      irradiated one.

PMID- 16810526
TI  - [Advance refusal of treatment in case of loss of autonomy due to persistent brain
      disease].
AB  - A short overview is given of the current debate on ethics and legal clarification
      of the range and binding force of so-called living wills demanding interruption
      of treatment in case of loss of autonomy due to persistent or progressive brain
      disease. Using the examples of dementia and persistent vegetative states -
      conditions with growing significance for psychiatrists - the binding force of
      living wills is examined for cases in which the irreversibility and extent of
      consciousness loss cannot be predicted with certainty. The range of living wills'
      authority appears also unclear. Legal proposals for limiting them to disease
      conditions near death are confronted by other proposals that reject such
      limitations. Added to this is the medical uncertainty of assessing the criterion
      nearness to death in irreversible and life-limiting diseases. The patient's right
      of self-determination, confirmed by high court decisions, to refuse in advance
      treatments that are life-prolonging but require consent is opposed to the medical
      obligation to save life and act in the patient's best interest. Moral dilemmas
      caused by this situation on the part of physicians, carepersons, and relatives or
      others, particularly authorized persons, should be solved by an exhaustive
      discussion with all persons who are involved in such decisions, and in a way that
      comes as near as possible to the patients living will.

PMID- 16810527
TI  - [Identification of pathologic alcohol use and its prevention. Results of employee
      interviews in a clinic].
AB  - After a short review of the literature about addiction in the working place, a
      study is presented that evaluates the alcohol use of all employees (n=301) in a
      clinic. The readiness to cooperate was very strong (72%). The openness
      (investigated with the FPI subscale for openness) was also satisfactory. Results
      showed a surprisingly high proportion of notable alcohol use by employees (26%).
      Especially the group of young female employees showed a high range of stress
      indicators: alcohol use (28.6%), nicotine (24.2%) and eating disorders (22.9%),
      and moderate-to-strong consumption of medication (12.1%). A sex-specific model of
      the development of addiction will be suggested based on these study results. A
      program of preventive measures was implemented integrating well-known components
      of established successful preventive measures and considering the special
      environment of the clinic.

PMID- 16810528
TI  - [Pharmacological aspects of therapeutic botulinum toxin preparations].
AB  - Therapeutic preparations of botulinum toxin (BT) consist of botulinum neurotoxin
      (BNT), complexing proteins, and excipients. Depending on the target tissue, BNT
      can block cholinergic neuromuscular innervation of intra- and extrafusal muscle
      fibres or cholinergic autonomic innervation of sweat, lacrimal, and salival
      glands and smooth muscles. Indirect CNS effects are numerous; direct ones have
      not been reported after intramuscular application. Botulinum toxin type A is
      distributed as Botox, Dysport, Xeomin, Hengli/CBTX-A, and Neuronox and BT type B
      as NeuroBloc/Myobloc. Differences in potency labelling of therapeutic BT
      preparations can be corrected by introduction of a conversion factor of 1:3
      between Botox and Dysport, of 1:1 between Botox and Xeomin, and of 1:40 between
      Botox and NeuroBloc/Myobloc. Acute adverse effects of BT can be obligate, local
      or systemic. Adverse effect profiles of the different preparations are similar.
      However, BT type B frequently produces additional autonomic systemic adverse
      effects. Long-term application does not produce additional adverse effects. BNT
      can be partially or completely blocked by antibodies. Risk factors include the
      amount of BNT applied at each injection series, the interval between injection
      series, and the specific biological potency (SBP) of the BT preparation used. The
      SBP is 5 equivalent mouse units/ng BNT for NeuroBloc, 60 for Botox, 100 for
      Dysport, and 167 for Xeomin. Xeomin should therefore have a particularly low
      antigenicity. Clinical confirmation of this predicition, however, is lacking.

PMID- 16810529
TI  - Instant gratification must wait.

PMID- 16810530
TI  - Will innervation imaging predict ventricular arrhythmias in ischaemic
      cardiomyopathy?

PMID- 16810531
TI  - Increased incidence of Lyme borreliosis in southern Sweden following mild winters
      and during warm, humid summers.
AB  - The aim of the present study was to investigate the long-term incidence rate of
      Lyme borreliosis and, additionally, to determine whether a correlation exists
      between climatic factors and summer-season variations in the incidence of Lyme
      borreliosis. Climatic variability acts directly on tick population dynamics and
      indirectly on human exposure to Lyme borreliosis spirochetes. In this study,
      conducted in primary healthcare clinics in southeastern Sweden, electronic
      patient records from 1997-2003 were searched for those that fulfilled the
      criteria for erythema migrans. Using a multilevel Poisson regression model, the
      influence of various climatic factors on the summer-season variations in the
      incidence of erythema migrans were studied. The mean annual incidence rate was
      464 cases of erythema migrans per 100,000 inhabitants. The incidence was
      significantly higher in women than in men, 505 and 423 cases per 100,000
      inhabitants, respectively (p<0.001). The summer-season variations in the erythema
      migrans incidence rate correlated with the monthly mean summer temperatures
      (incidence rate ratio 1.12; p<0.001), the number of winter days with temperatures
      below 0 degrees C (incidence rate ratio 0.97; p<0.001), the monthly mean summer
      precipitation (incidence rate ratio 0.92; p<0.05), and the number of summer days
      with relative humidity above 86% (incidence rate ratio 1.04; p<0.05). In
      conclusion, Lyme borreliosis is highly endemic in southeastern Sweden. The
      climate in this area, which is favourable not only for human tick exposure but
      also for the abundance of host-seeking ticks, influences the summer-season
      variations in the incidence of Lyme borreliosis.

PMID- 16810532
TI  - In vitro quantitative light-induced fluorescence to measure changes in enamel
      mineralization.
AB  - A sensitive, quantitative method for investigating changes in enamel
      mineralization of specimens subjected to in vitro or in situ experimentation is
      presented. The fluorescence-detecting instrument integrates a Xenon arc light
      source and an object positioning stage, which makes it particularly suitable for
      the nondestructive assessment of demineralized or remineralized enamel. We
      demonstrate the ability of in vitro quantitative light-induced fluorescence (QLF)
      to quantify changes in mineralization of bovine enamel discs that had been
      exposed in vitro to a demineralizing gel (n=36) or biofilm-mediated
      demineralization challenges (n=10), or were carried in situ by three volunteers
      during a 10-day experiment (n=12). Further experiments show the technique's value
      for monitoring the extent of remineralization in 36 specimens exposed in vitro to
      oral multispecies biofilms and document the repeatability of in vitro QLF
      measurements (n=10) under standardized assay conditions. The validity of the
      method is illustrated by comparison with transversal microradiography (TMR), the
      invasive current gold standard for assessing experimental changes in enamel
      mineralization. Ten discs with 22 measurement areas for comparison demonstrated a
      positive correlation between TMR and QLF (r=0.82). Filling a technological gap,
      this QLF system is a promising tool to assay in vitro nondestructively localized
      changes in mineralization of enamel specimens.

PMID- 16810533
TI  - [Treatment of infected total knee arthroplasty. When does implant salvage make
      sense?].
AB  - Infection of a total knee arthroplasty can be classified as acute, chronic and
      haematogenic with and without implant loosening. A differentiated treatment
      concept for all types of infection is necessary. Furthermore, specific treatment
      has to be initiated early, as any delay is associated with a worsening of the
      prognosis. Treatment of infection with implant salvage may be one therapeutic
      option if the implant is not loose. According to the current literature, therapy
      with retention of the prosthesis may be promising: (1) in the case of early
      infection (<3 weeks of ongoing symptoms), (2) with unconstrained implants, (3) in
      the case of infection with a single organism that is susceptible to antibiotic
      therapy, (4) if soft tissue coverage is not affected, and (5) if the immune
      system is not compromised. Chronic infections, (semi-)constrained implants and
      soft tissue defects have to be considered as contraindications and implants
      should be removed. Early and consequent therapy with operative debridement and
      specific long-term antibiotic therapy are necessary to achieve implant salvage.
      The additional application of antibiotics addressing bacterial biofilms have
      helped to improve the prognosis. Due to the fact that revision arthroplasty is
      often associated with limited function after infection of the total knee joint,
      retention of the implant has to be considered a therapeutic alternative in early
      infection.

PMID- 16810534
TI  - [Periprosthetic knee infection. One-stage exchange].
AB  - Systematic diagnostics and successful therapy of periprosthetic infection of the
      knee can only be achieved under optimal conditions. History, clinical examination
      and an elevated CRP level are the basis for suspicion of infection. Diagnosis is
      confirmed by identification of the pathogen through aspiration of the joint under
      sterile conditions. The microbiological examination is done in a laboratory,
      which is specialised in foreign body infections. Identification of the causing
      pathogens and their resistance pattern are essential to determine the topical and
      systemic course of antibiotics. When these conditions are fulfilled, the one
      stage exchange procedure offers great advantages in comparison with procedures
      performed in two or more stages for all those involved--patients, surgeons and
      health care systems--while providing the same chance of a successful elimination
      of the infection, with an even better functional outcome. Currently, the
      treatment costs are not adequately reimbursed. In the future, prompt treatment of
      these especially unfortunate patients will only be possible, if the tremendous
      resources consumed by these patients are fully covered.

PMID- 16810535
TI  - [Hyaluronic acid in the therapy of arthrosis].

PMID- 16810536
TI  - The effect of hormone replacement therapy on the levels of serum lipids,
      apolipoprotein AI, apolipoprotein B and lipoprotein (a) in Turkish postmenopausal
      women.
AB  - OBJECTIVES: Estrogen replacement therapy alters the lipid profiles favorably for
      delaying atherosclerosis in postmenopausal women. The effects of estrogen plus
      progesterone combination therapy on lipids are controversial. This study was
      designed to evaluate the effect of female sex hormones on lipids and lipoproteins
      and to clarify the influence of progesterone on the effect of estrogen in
      postmenopausal women. METHODS: Of the 60 postmenopausal women admitted to our
      menopause clinic, 40 had intact uterus and received continuous 0.625 mg
      conjugated equine estrogen (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA),
      whereas the remaining 20 were hysterectomized and received 0.625 mg CEE daily. To
      assess the alterations in lipids and lipoproteins during menopause, 45 healthy
      premenopausal women were investigated. Lipid and lipoprotein levels were assessed
      in each subject at baseline and at the 6th and 18th months of therapy. RESULTS:
      In menopause, a shift towards more atherogenic lipid and lipoprotein profiles
      than those of the premenopausal state was found. Following 18 months of
      treatment, both regimens reduced total cholesterol (TC) levels as compared with
      the baseline (6.4 vs. 6.9% in the CEE/MPA and CEE groups, respectively). The CEE
      group had a more pronounced increase in high-density lipoprotein (HDL)
      cholesterol than the CEE/MPA group (10.3 vs. 8.8%, respectively). Both groups
      displayed reduced TC, low-density lipoprotein (LDL) cholesterol and
      apolipoprotein-B (ApoB) concentrations, whereas triglycerides increased, with a
      greater tendency to increase in the CEE/MPA group at the end of the trial. Also,
      the lipoprotein (a) [Lp(a)] levels decreased significantly (27.6 vs. 24.5% in the
      CEE/MPA and CEE groups, respectively). This decrease was more pronounced in
      subjects with a relatively higher basal Lp(a) concentration. CONCLUSION: Both
      treatment regimens caused positive alterations in the lipid and lipoprotein
      profiles. This association might play a pivotal role in the postmenopausal
      increases in atherosclerotic diseases and cardioprotective effect of estrogen in
      postmenopausal women.

PMID- 16810538
TI  - [Sepsis. Update on pathophysiology, diagnostics and therapy].
AB  - Sepsis results from the host response to infection. While a localized and
      controlled inflammatory reaction helps to control infection, a dysregulated
      response may lead to multiple organ failure and determines the course and
      prognosis of the septic patient. Despite intensive care, mortality remains as
      high as 54% for severe sepsis and septic shock. As the mechanisms are becoming
      better defined, interventions aiming to interfere with the host response have
      been undertaken, largely with disappointing results. Thus, many evidence-based
      recommendations suggest waiving of resource-consuming interventions.
      Nevertheless, several seminal studies have indicated that early and systematic
      supportive therapy according to pathophysiological principles, most notably early
      goal-directed therapy, low-dose hydrocortisone and activated protein C, can
      disrupt dysfunctional cascades and can favourably influence the course of the
      disease. In parallel, efforts to better define nationwide epidemiology and
      treatment habits for severe sepsis by the German competence network "SepNet"
      indicate that therapy of severe sepsis is generally in poor compliance with
      guidelines, while the personal perception of physicians in charge would suggest
      high rates of adherence. Thus, strategies of change management, such as
      implementation of sepsis bundles are warranted to achieve a better standard of
      care toward the aim of the "surviving sepsis campaign", i.e. a reduction of
      mortality by 25% within the next 5 years.

PMID- 16810539
TI  - [Acute myopia and progressive acute renal failure in a 28-year old active
      horsewoman].
AB  - A 28-year old active sportswoman was admitted to hospital suffering from fever,
      menigeal irritation, acute myopia and progressive acute renal failure. Showing
      signs of polyserositis in combination with pulmonary granulomatous changes a
      collagenosis as well as an atypical pneumonia was excluded first. Due to the
      renal loss of function a renal biopsy was taken with the typical histological
      result of a hantavirus infection. This could be confirmed serologically in the
      following. With symptomatic treatment the patient had an uneventful complete
      recovery during the next four weeks.

PMID- 16810540
TI  - Diagnosing an extra-axial chordoma of the proximal tibia with the help of
      brachyury, a molecule required for notochordal differentiation.
AB  - Chordomas are rare malignant bone tumours considered to arise from notochordal
      remnants that persist in the axial skeleton. Although their morphology can
      resemble that of a carcinoma, chondrosarcoma or malignant melanoma, the axial
      location and their well-defined immunophenotype, including expression of
      cytokeratins (CK7/20/8/18/19) and S100, generally allow the diagnosis to be made
      with confidence once the possibility is considered. In contrast, making a robust
      diagnosis of an extra-axial chordoma has been difficult in the absence of
      specific markers for chordomas. We have recently shown in gene expression
      microarray and immunohistochemistry studies that brachyury, a transcription
      factor crucial for notochordal development, is a specific and sensitive maker for
      chordomas. We now present a case of an intracortical tibial tumour, with detailed
      report of the imaging, and morphological features consistent with a chordoma,
      where notochordal differentiation was demonstrated with an antibody to brachyury.
      The tumour cells were also positive for cytokeratins, including CK19, and S100,
      CEA, EMA and HMBE1, findings which support the diagnosis of chordoma. Brachyury
      can be employed as a marker of notochordal differentiation and help identify
      confidently, for the first time, extra-axial bone and soft tissue chordomas, and
      tumours which may show focal notochordal differentiation.

PMID- 16810541
TI  - Dynamic magnetic resonance imaging of muscle function after surgery.

PMID- 16810542
TI  - The effectiveness of reinfusion after total knee replacement. A prospective
      randomised controlled study.
AB  - The purpose of our study was to determine the effectiveness of a postoperative
      autologous blood reinfusion system as an alternative to homologous, banked blood
      transfusions in total knee arthroplasty. We carried out a prospective randomised
      controlled study on 60 patients having unilateral total knee replacements. In all
      these patients, the same surgical team applied the same surgical technique, and
      all patients followed the same rehabilitation program. In 30 of these patients
      (group A), a reinfusion system of unwashed salvaged blood was applied, and they
      were supplemented postoperatively with banked blood transfusions when required. A
      control group of 30 patients (group B), in whom standard suction drains were
      used, received one unit of homologous banked blood transfusion intraoperatively
      and additional blood transfusions postoperatively when required. The
      administration of banked blood transfusion was determined by the haemoglobin
      value (<9 mg/dl) and/or clinical signs (blood pressure, pulse, etc.). The values
      of haemoglobin, haematocrit and platelets were recorded preoperatively and the
      first, fifth and 15th postoperative days, respectively. Five patients of group A
      required nine units of homologous blood (0.3 units/patient) postoperatively. Ten
      patients of group B required an additional 15 banked blood units postoperatively
      (in total 45 banked blood units for group B; 1.5 units/patient). In the study
      group, the total homologous blood requirements were reduced by 80%, while the
      postoperative blood requirements were reduced by 50%. There was no significant
      difference in the postoperative haematocrit and haemoglobin values between the
      two groups. The cost of the blood management in the study group was reduced by
      36%. The use of an autologous blood reinfusion system reduces highly effectively
      the demands of homologous banked blood transfusion in total knee arthroplasty.

PMID- 16810543
TI  - Survivin expression in pre-invasive lesions and non-small cell lung carcinoma.
AB  - Survivin is an inhibitor of apoptosis protein, which is overexpressed in many
      carcinomas, including lung carcinoma. The aim of this immunohistochemical study
      was to investigate the role of survivin in the early steps of lung carcinogenesis
      and non-small cell lung carcinomas (NSCLC), and its relationship with expression
      of p53 protein, a tumor suppressor gene involved in cell cycle control. In the
      normal bronchial epithelium, low-grade atypical adenomatous hyperplasia (AAH) and
      non-neoplastic lung parenchyma adjacent to tumor, survivin was found completely
      negative. Expression of survivin was detected in the areas of squamous metaplasia
      and dysplasia as well as high-grade AAH lesions adjacent to tumor. Survivin was
      expressed in 50 (64%) and p53 in 41 (53%) NSCLC. Survivin expression was
      significantly correlated with lymph node metastasis (p=0.02). There was no
      correlation between survivin and p53 expression. The patients with expression of
      survivin had significantly worse prognosis (Log-rank test, p=0.003). Multivariate
      Cox regression analysis showed TNM stage (p<0.001) and survivin expression
      (p=0.003) as independent prognostic indicators. In conclusion, survivin
      expression might be an early step in lung carcinogenesis. Survivin expression
      might also be used as a prognostic indicator predicting the worse outcome in
      NSCLC, and might be a novel target for the treatment of patients with preinvasive
      lesions of lung and NSCLC.

PMID- 16810544
TI  - Hyponatremia associated with adenovirus infection in twin infants.

PMID- 16810545
TI  - Preplanning for correctional osteotomies: sculpture your result.
AB  - Traditionally, correctional osteotomies are pre-planned on paper, but there is
      also the possibility of assembling a stereolithographic model from CT-scan data
      or even employing computer-assisted 3D virtual osteotomy systems for the more
      complicated cases. The simplicity of the one was combined with the extra
      dimension of the other. This resulted in a method where preplanning was performed
      with a clayed model. With a case report of a posttraumatic malunion, the
      procedure is illustrated for a correctional osteotomy in the proximal femur.

PMID- 16810546
TI  - Benign giant cell tumor of the spine: an unusual indication for radiotherapy.
AB  - INTRODUCTION: Giant cell tumors are rare primary bone tumors. Multicentricity as
      well as spinal localization is extremely rare. CASE REPORT: We report about a 64
      year-old female patient presenting with history of three osseous and one pulmonal
      manifestation of a benign giant cell tumor that have manifested metachronously
      within 23 years. The two periphery bone and the one pulmonal manifestation were
      treated surgically with success. Now, a further osseous lesion occurred at the
      seventh vertebra of the thoracic spine and was treated by dorsal instrumentation
      and replacement of the seventh vertebra. Nine months later, local recurrence of
      this benign giant cell tumor developed at the thoracic spine and was treated with
      radiotherapy with a total dose of 45 Gy. Three months after salvage radiotherapy
      definite local progress occurred localized within the former radiation treatment
      field. Due to neurological deficits a laminectomy and a stabilization of the
      destroyed sixth vertebra with bone cement was carried out. Histopathological
      examination again showed benign giant cell tumor without suspicion of malignancy.
      CONCLUSION: In the literature the use of radiation therapy remains an appropriate
      therapy option in benign giant cell tumors with minimal adverse sequelae if
      primary surgical treatment is not feasible or fails. In cases of definitive
      radiotherapy a total dose > 45 Gy should be discussed.

PMID- 16810547
TI  - Fracture of ceramic heads in total hip replacement.
AB  - After introduction of ceramics in total hip replacement, there have been several
      studies on wear and fracture of the femoral head component. Though reports on
      fractures are few, we saw four fractures within 2 months. In all patients, a
      cementless hip prosthesis by four different surgeons was implanted between 3/2001
      and 2/2004. In three patients, a ceramic-on-polyethylene pair and in one, a
      ceramic-on-ceramic pair was used. Only one patient suffered an adequate trauma.
      The mean survival of the ceramic head was 27 months (11-42). In two patients with
      polyethylene inlays, the inlay showed signs of wear out due to the fractured
      head. All four revision surgeries had a good outcome with satisfying results and
      no complications. Though we observe the postoperative development after
      implantation of ceramic components closely, we still believe that ceramics in
      total hip replacement in young and active patients are indicated with good long
      term results.

PMID- 16810548
TI  - Peroperative difficulties in fluoroscopy of the femoral head in massive obese
      patient: enhanced visualization by intra-articular contrast agent.
AB  - Peroperative fluoroscopic visualization of the femoral head in massive obese
      patient can be enhanced by the administration of intra-articular contrast agent
      into the hip joint. It provides safe alternative for compromised resolution
      during the introduction of femoral head screws. We report our experiences with
      one patient as a technical report and believe that in certain cases this method
      may be quite helpful.

PMID- 16810549
TI  - Hip joint remodeling in an adult following excision of a giant cell tumor
      involving the acetabulum: a case report and literature review.
AB  - We describe a 47-year-old man with a giant cell tumor of bone involving the
      acetabulum treated with curettage and bone grafting which resulted in good
      remodeling of the hip joint. The patient had a 15 x 18-cm(2) mass lesion
      extending from the right ischium to the acetabulum. Treatment included curettage,
      phenol, and ethanol application as an adjuvant, and cancellous bone allografting
      was performed on the subchondral area of the acetabulum. The posterior column of
      the acetabulum was disappeared by tumor invasion. Despite central migration of
      the femoral head, adequate hip joint repair was achieved without surgery 5.5
      years postoperatively and with no tumor recurrence. The patient could walk
      without pain or ambulation aids; hip range of motion was 100 degrees for flexion,
      0 degrees for extension, 30 degrees for abduction, 45 degrees for external
      rotation, and 10 degrees for internal rotation, and the functional result was
      93.3% in the Enneking scoring system. We performed intralesional curettage with
      phenol and ethanol adjuvant therapy for pelvic giant cell tumor without tumor
      recurrence, and good repair of a hip joint adaptation can be achieved even in an
      adult patient.

PMID- 16810550
TI  - Increased polyethylene wear after cementless ABG I total hip arthroplasty.
AB  - INTRODUCTION: The cementless, hydroxyapatite-coated Anatomique Benoist Giraud-I
      (ABG-I) hip endoprosthesis represented a modern implant in the 1990s. The aim of
      the current retrospective study was to evaluate the clinical and radiological
      results of this prosthesis. In addition, an analysis of the complications and
      retrieved implants was conducted. MATERIALS/METHODS: The medium-term results
      (follow-up 5.23 years) of 193 hip joints are presented. Of 158 total cohorts,
      81.9% was able to undergo follow-up performed with standardized clinical and
      radiological investigations. Physical characteristics of the patients and the
      underlying disease prompting the need for total hip arthroplasty, as well as a
      clinical score (Merle d'Aubigne) were recorded. At the time of follow-up, a
      radiologic examination of all patients with a standardized evaluation was
      performed. In addition, the migration of the acetabular cup and femoral head as
      well as polyethylene wear could be determined digitally in 118 cases (61.1%)
      using one-picture Roentgen analysis. RESULTS: Clinical results, as measured with
      a Merle d'Aubigne Score increase from 8.4 to 16.2, were very good. Radiographs
      demonstrated successful osseous integration of the anatomically molded shaft.
      Within the period of the investigation, no revision procedures of the femoral
      shaft were necessary. However, the rate of polyethylene abrasion of 0.23 mm/year
      was markedly high. 13.9% of hips (n = 27) required acetabular cup revision due to
      wear. This calculates to a prosthesis 7-year survival probability of 63%.
      Intraoperative findings during the revision cases showed extensive periacetabular
      osteolysis with foreign body granulation tissue. Analysis of data from the total
      patient cohort versus data from cases requiring revision showed a significantly
      increased frequency of high polyethylene wear in young active patients as well as
      in cases where an unfavorable acetabular cup to femoral head relation existed in
      correspondence with polyethylene thickness. There is evidence, however, that
      suggests that multifactorial causes for the increased wear are significant in
      regards to the principal material and technical features of the prosthesis.
      CONCLUSION: On the basis of these results, it is strongly recommended that all
      patients treated with an ABG-I hip endoprosthesis should receive close clinical
      and most importantly close radiologic follow-up.

PMID- 16810551
TI  - Shoulder impairment following treatment of diaphysial fractures of humerus by
      functional brace.
AB  - INTRODUCTION: Treatment of humeral shaft fractures by functional bracing has been
      reported to be effective in achieving high rate of fracture union and good
      function of the adjacent shoulder and elbow joints. Since our previous clinical
      impression indicated an occurrence of shoulder function impairment following this
      treatment, we investigated the shoulder function in a consecutive series of
      patients treated by functional bracing for fractures of humeral shaft in order to
      estimate their residual shoulder function. MATERIALS AND METHODS: We followed 15
      consecutive patients with humeral shaft fractures treated by functional brace.
      The mean follow up was 30 months (range 12-57 months); seven patients with
      midshaft fracture, four patients with proximal third, and four patients with
      fractured distal third of the humeral diaphysis. All the patients were evaluated
      by the Constant score of the injured limb in comparison to the contra-lateral not
      injured shoulder and by the Oxford shoulder score of the injured limb. RESULTS:
      We found that all the fractures were united with mean varus angulation of 13
      degrees and with mean angulation in the saggital plane of 9 degrees antecurvatum,
      Constant scores were significantly lower in the injured shoulders (P < 0.001) and
      the function of the shoulders in the injured extremities were estimated as having
      mean Oxford shoulder score of 34 (range 17-54). CONCLUSIONS: The evaluation of
      the present series revealed an impaired functional outcome in the shoulders after
      humeral shaft fracture. Our results indicate that although the fracture union is
      usually achieved following the functional bracing of humeral shaft fractures, the
      shoulder function in the injured limb may remain impaired.

PMID- 16810552
TI  - False aneurysm of the left femoral artery and thrombosis of the left femoral vein
      after total hip arthroplasty.
AB  - We report a 75-year-old male patient with an aneurysm of the left femoral artery
      after cemented total hip arthroplasty. Two months after the operation, the
      patient showed a spherical resistance and pain in the left groin. Examination
      showed a big false aneurysm of the left femoral artery. After resection of the
      aneurysm, an endovascular stent graft vessel prosthesis was implanted. The
      aneurysm originated from a punctual lesion of the artery caused by a screw. Since
      the first description of vessel lesions in orthopaedic surgery in 1964, a total
      of 24 cases of aneurysm in hip surgery have been described. Therefore, a review
      of literature tries to explain causes and mechanisms of vessel injuries in hip
      surgery and the possibilities of repair.

PMID- 16810553
TI  - Infection prophylaxis: a prospective study in 106 patients operated on by tibial
      osteotomy using the hemicallotasis technique.
AB  - INTRODUCTION: Tibial osteotomy by the hemicallotasis technique is a clean
      elective operation. With external fixation pins inserted, close to the knee
      joint, the infection prophylaxis should be considered. The primary aim was to
      investigate the differences in the postoperative use of antibiotics during the
      time in external fixation between administrating prophylactic antibiotics for 3
      days or as a single dose in patients operated on by the hemicallotasis technique
      for knee deformities. Secondary aims were to study the differences in pin-site
      infection rate and grade and complications. MATERIAL AND METHODS: A total of 106
      consecutive patients of mean age 52 years (range 18-69) operated on by the
      hemicallotasis technique for knee deformities were included in this prospective
      study. Sixty patients were prescribed prophylactic antibiotics for 3 days and 46
      patients as a single dose. Chlorhexidine (5 mg/ml) in alcohol (70% ethanol) was
      used as cleansing agent in the pin-site care. The power of the study was
      calculated to 80% to detect a difference in the postoperative use of antibiotics
      for 7 days during the treatment in external fixation. RESULTS: There were no
      differences in postoperative use of antibiotics between 3 days administration or
      a single dose of prophylactic antibiotics. This was the case with infection rate
      and grade, positive bacterial cultures, presence of Staphylococcus aureus, nor
      positive culturing from the tip of the pins at removal. Neither were there any
      differences in numbers of loose pins and complications. CONCLUSION: There were no
      differences between 3 days of administration of prophylactic antibiotics and one
      single dose. One single dose of prophylactic antibiotics is appropriate together
      with a pin-site concept preventing pin-site infection in patients operated on by
      hemicallotasis osteotomy.

PMID- 16810554
TI  - Misinterpretation of cup anteversion in total hip arthroplasty using planar
      radiography.
AB  - INTRODUCTION: Anteroposterior pelvic radiographs are routinely used to monitor
      cup orientation in total hip arthroplasty (THA). Analysis of planar radiographs
      leads to a certain degree of measurement error for the cup anteversion (AV). With
      the current study, we wanted to clarify whether planar radiography can be used
      for accurate evaluation of the THA position. MATERIALS AND METHODS: The
      postoperative orientation of pelvic implants in 42 patients was analyzed
      according to five documented mathematical algorithms using planar radiographs.
      Postoperative computed tomography (CT) pelvis scans were available for all
      patients. A CT-based navigation system was used to determine AV. RESULTS: The
      comparison showed that all five formulas presented substantial variations for the
      AV angle. Of these, Widmer's algorithm presented the smallest difference compared
      to the CT. Misinterpretation of postoperative planar radiographs is a common
      problem in THA. CONCLUSION: Planar radiographs are too imprecise for exact
      evaluation of the correct cup AV after THA. CT-based analysis may be necessary if
      exact values are required.

PMID- 16810555
TI  - Retrograde nailing with subsequent screw fixation for ipsilateral femoral shaft
      and neck fractures.
AB  - INTRODUCTION: Although ipsilateral femoral shaft and neck fractures are difficult
      to treat, there is still no consensus on the optimal treatment of this complex
      injury. We report the results of treating the 17 fractures with a standard
      protocol of retrograde nailing for diaphyseal fractures and subsequent screw
      fixation for the femoral neck fractures. MATERIALS AND METHODS: Seventeen
      injuries (16 patients) sustained femoral shaft fractures, which were treated with
      retrograde intramedullary nails and subsequent screw fixation. Femoral neck
      fracture was noted before the operation in all patients except one. A femoral
      shaft fracture was always addressed first with unreamed retrograde nailing. Then,
      the femoral neck fracture was treated by cannulated screws or dynamic hip screw
      according to the level of fracture. RESULTS: The average time for union of
      femoral shaft fractures was 27.3 (14-60) weeks. Nonunion occurred in five
      patients, who required bone grafts or changes of fixation. The average time for
      union of femoral neck fractures was 11 (8-12) weeks. All united, except for one
      case of nonunion with avascuar necrosis, which was a Garden stage IV fracture.
      Functional results using Friedman-Wyman criteria were good in 16 cases, and fair
      in one. The only fair result was nonunion of the femoral neck, which had the
      joint arthroplasty. CONCLUSION: Retrograde nailing of femoral shaft fractures can
      provide an easy fixation and a favorable result for ipsilateral femoral neck
      fractures.

PMID- 16810556
TI  - Parecoxib impairs early metaphyseal bone healing in rats.
AB  - INTRODUCTION: Cox2 inhibitors decrease prostaglandin production and therefore
      influence bone healing especially in unstable long bone models. It is unclear to
      what extent implant fixation in stable metaphyseal bone is impaired. METHOD: Male
      rats numbering 30 and female rats numbering 40 received a stainless steel screw
      in the metaphyseal bone of the proximal tibia. Half of the rats were treated with
      6.4 mg/kg BW parecoxib by continuous release from a subcutaneous mini pump during
      7 or 14 days. After treatment, the pull out force, stiffness, and pull out energy
      of the screw were measured. RESULTS: No effect of parecoxib on the pull out force
      was found for male rats. In female rats the pull out force was decreased by 16%
      (P = 0.03) after 7 days treatment with parecoxib. This effect had disappeared
      after 14 days. CONCLUSION: Adverse effects of parecoxib on the early phase
      healing of metaphyseal bone in female rats are small and were not detectable
      after 14 days. No effect was seen in male rats, possibly due to a faster
      metabolic elimination of the drug.

PMID- 16810557
TI  - IL-4 inhibits the TNF-alpha induced proliferation of renal cell carcinoma (RCC)
      and cooperates with TNF-alpha to induce apoptotic and cytokine responses by RCC:
      implications for antitumor immune responses.
AB  - OBJECTIVE: While previous reports clearly demonstrated antiproliferative effects
      of IL-4 on renal cell carcinoma (RCC) in vitro, the administration of IL-4 to
      patients with metastatic RCC in clinical trials could not recapitulate the
      promising preclinical results. In the present study we wanted to examine the
      context of IL-4 action and to establish conditions of enhanced IL-4 efficacy.
      METHODS: Primary and permanent human RCC cells were cultured in either serum
      supplemented or chemically defined, serum-free culture medium in the presence or
      absence of cytokines. Cell proliferation was assessed as [(3)H]-thymidine
      incorporation. Cell apoptosis was measured using the fluorescent DNA intercalator
      7-aminoactinomycin D and flow cytometry. In addition, culture media conditioned
      by RCC were subjected to cytokine antibody array and cytokine multiplex analysis.
      RESULTS: Our results indicate that the previously reported antiproliferative
      effects of IL-4 are serum-dependent. Under serum-free conditions, IL-4 failed to
      exhibit growth-inhibitory effects or was even growth-stimulatory. In a chemically
      defined, serum-free medium (AIM-V), however, IL-4 inhibited the TNF-alpha induced
      proliferation of RCC. IL-4 and TNF-alpha synergistically induced apoptosis of RCC
      as well as a complex cytokine response by RCC, which included the synergistic
      upregulation of RANTES and MCP-1. CONCLUSIONS: IL-4 alone has little effect on
      the spontaneous proliferation of RCC but can prevent the enhancement of
      proliferation induced by growth promoters like FBS and TNF-alpha. The concomitant
      growth inhibitory, apoptosis-inducing, and cytokine-enhancing effects of IL-4 in
      combination with TNF-alpha on RCC support the view that Th2 cytokines may be
      required for productive immune responses against RCC.

PMID- 16810559
TI  - External review of health plan denials of mental health services: lessons from
      Minnesota.
AB  - There has been concern that health plans unfairly deny claims for mental health
      services. This study examines a unique Minnesota program that resulted from a
      legal settlement. An independent panel reviews all mental health service denials
      in the state's three largest health plans. Our study analyzed every case file (N
      = 4717) the panel reviewed from January 2002 to August 2005. This unique dataset
      provides insight into health plan behavior. The findings show that the panel
      reversed only 2.9% of denied claims, suggesting inappropriate denials were rare.
      However, the panel decisions have made important improvements in contract
      language and patient communications.

PMID- 16810558
TI  - Diazepam pharamacokinetics from preclinical to phase I using a Bayesian
      population physiologically based pharmacokinetic model with informative prior
      distributions in WinBUGS.
AB  - Modelling is an important applied tool in drug discovery and development for the
      prediction and interpretation of drug pharmacokinetics. Preclinical information
      is used to decide whether a compound will be taken forwards and its
      pharmacokinetics investigated in human. After proceeding to human little to no
      use is made of these often very rich data. We suggest a method where the
      preclinical data are integrated into a whole body physiologically based
      pharmacokinetic (WBPBPK) model and this model is then used for estimating
      population PK parameters in human. This approach offers a continuous flow of
      information from preclinical to clinical studies without the need for different
      models or model reduction. Additionally, predictions are based upon single
      parameter values, but making realistic predictions involves incorporating the
      various sources of variability and uncertainty. Currently, WBPBPK modelling is
      undertaken as a two-stage process: (i) estimation (optimisation) of drug
      dependent parameters by either least squares regression or maximum likelihood and
      (ii) accounting for the existing parameter variability and uncertainty by
      stochastic simulation. To address these issues a general Bayesian approach using
      WinBUGS for estimation of drug-dependent parameters in WBPBPK models is
      described. Initially applied to data in rat, this approach is further adopted for
      extrapolation to human, which allows retention of some parameters and updating
      others with the available human data. While the issues surrounding the
      incorporation of uncertainty and variability within prediction have been explored
      within WBPBPK modeling methodology they have equal application to other areas of
      pharmacokinetics, as well as to pharmacodynamics.

PMID- 16810561
TI  - Evaluation of oxidative stress and inflammation in long term Brucella melitensis
      infection.
AB  - The Brucella genus is able to cause chronic infection in a wide range of mammals
      including humans. Oxidative events, lipid peroxidation and inflammatory response
      against Brucella infection have not yet been well elucidated in vivo. We have
      investigated oxidative/antioxidative status and nitric oxide production in
      plasma, brain, liver and spleen during a 60 day period of B. melitensis infection
      in a rat model. In addition, inducible nitric oxide synthase (iNOS), IL-10, IL
      12, IFN-gamma and TNF-alpha mRNA transcriptions were analyzed by semiquantitative
      reverse transcriptase PCR (RT-PCR) in brain samples. Animals were infected with
      B. melitensis and sacrificed at 7th, 15th, 30th, 45th and 60th day of post
      inoculation. Malondialdehyde (MDA), as an indicator of lipid peroxidation, and
      nitric oxide (NO) concentrations were significantly increased after Brucella
      inoculation and began to decline to basal levels from 45th day in plasma, liver
      and spleen. However, iNOS transcription was not induced during the infection
      period in brains. In contrast, MDA level was increased in brain during the late
      phase of infection without any change in NO production. The infection did not
      alter the antioxidant enzyme activities in the tissues; although significantly
      increased catalase activity was observed between days 30 and 45 in the liver.
      Transcription analyses demonstrated that IL-10, IL-12 and IFN-gamma mRNA level
      were not induced in the brain. Only TNF-alpha mRNA was weakly up-regulated in
      brain 30 days after pathogen inoculation. The results obtained in this study
      demonstrate that B. melitensis induces lipid peroxidation and NO production in
      the liver and spleen in the early days of infection, but that these levels
      subsequently decline. Moreover, Brucella does not appear to induce antioxidant
      enzyme activities and inflammation during two months of infection. However, the
      pathogen does stimulate cerebral lipid peroxidation in the late phase of
      infection without causing significant inflammation.

PMID- 16810562
TI  - Frying stability of Moringa stenopetala seed oil.
AB  - The frying performance of Moringa stenopetala seed oil (extracted with cold press
      or n-hexane) was studied especially as regards repeated frying operations. The
      oils were used for intermittent frying of potato slices and cod filets at a
      temperature of 175 degrees C for 5 consecutive days (5 fryings per day). The
      chemical changes occurring in oils were evaluated. Free fatty acid content, polar
      compounds, colour and viscosity of the oils all increased, whereas the iodine
      value, smoke point, polyunsaturated fatty acid content, induction period and
      tocopherol content decreased. The effect of the oil on the organoleptic quality
      of these fried foods and the theoretical number of frying operations possible
      before having to discard the oil was also determined. The analytical and sensory
      data showed that the lowest deterioration occurred in cold press produced oil.

PMID- 16810563
TI  - Postischemic alterations of BDNF, NGF, HSP 70 and ubiquitin immunoreactivity in
      the gerbil hippocampus: pharmacological approach.
AB  - 1. We investigated the immunohistochemical alterations of BDNF, NGF, HSP 70 and
      ubiquitin in the hippocampus 1 h to 14 days after transient cerebral ischemia in
      gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A
      (HMG-CoA) reductase inhibitor pitavastatin against the changes of BDNF, NGF, HSP
      70 and ubiquitin in the hippocampus after cerebral ischemia in the hippocampus
      after ischemia. 2. The transient cerebral ischemia was carried out by clamping
      the carotid arteries with aneurismal clips for 5 min. 3. In the present study,
      the alteration of HSP 70 and ubiquitin immunoreactivity in the hippocampal CA1
      sector was more pronounced than that of BDNF and NGF immunoreactivity after
      transient cerebral ischemia. In double-labeled immunostainings, BDNF, NGF and
      ubiquitin immunostaining was observed both in GFAP-positive astrocytes and MRF-1
      positive microglia in the hippocampal CA1 sector after ischemia. Furthermore,
      prophylactic treatment with pitavastatin prevented the damage of neurons with
      neurotrophic factor and stress proteins in the hippocampal CA1 sector after
      ischemia. 4. These findings suggest that the expression of stress protein
      including HSP 70 and ubiquitin may play a key role in the protection against the
      hippocampal CA1 neuronal damage after transient cerebral ischemia in comparison
      with the expression of neurotrophic factor such as BDNF and NGF. The present
      findings also suggest that the glial BDNF, NGF and ubiquitin may play some role
      for helping surviving neurons after ischemia. Furthermore, our present study
      indicates that prophylactic treatment with pitavastatin can prevent the damage of
      neurons with neurotrophic factor and stress proteins in the hippocampal CA1
      sector after transient cerebral ischemia. Thus our study provides further
      valuable information for the pathogenesis after transient cerebral ischemia.

PMID- 16810564
TI  - The collateral effects of joint attention training on social initiations,
      positive affect, imitation, and spontaneous speech for young children with
      autism.
AB  - Joint attention may be a core deficit in autism which underlies the abnormal
      development of later emerging social-communication behaviors. Given this theory,
      researchers have suggested that teaching young children with autism to engage in
      joint attention may lead to collateral increases in other non-targeted social
      communication behaviors. In this study, children with autism participated in a 10
      week joint attention training program and collateral changes in non-targeted
      behaviors were assessed. Following participation in the intervention, positive
      collateral changes were observed in social initiations, positive affect,
      imitation, play, and spontaneous speech. Results support the hypothesis that
      teaching joint attention skills leads to improvement in a variety of related
      skills and have implications for the treatment of young children with autism.

PMID- 16810565
TI  - Matching FCE activities and work demands: an explorative study.
AB  - OBJECTIVES: to explore to what extent the standardized Isernhagen Work Systems
      Functional Capacity Evaluation (IWS FCE) can be matched with observed work
      demands in workers with chronic low back pain, and, secondly, to explore whether
      this match can predict sick leave in the year after rehabilitation treatment.
      METHODS: An explorative prognostic cohort study with a one-year follow-up (four,
      eight and twelve months after baseline) was performed (n = 18). Demographics,
      back complaints and FCE performance were assessed at baseline. In addition, a
      workplace assessment (WPA) was performed. Eleven FCE activities were matched with
      work demands. Sick leave associated with low back pain and physical and
      psychosocial work demands were assessed during follow-up. RESULTS: Seven
      activities could be directly matched with WPA data. (Carrying, pushing, pulling,
      crouching, kneeling, static forward bending, and dynamic bending and rotating.)
      For some workers, difficulties existed in matching three of the activities
      (pushing, pulling and crouching). One activity (lifting) could indirectly be
      matched with WPA data. One activity (walking) could not be matched with WPA data.
      Two activities (sitting, standing) were excluded from analyses due to practical
      limitations. No relation was found between FCE performance, work demands, and
      sick leave during follow-up. CONCLUSIONS: Seven FCE activities could be directly
      matched with work demands. However, not all observed work demands could be
      matched with IWS FCE activities in the eighteen occupations studied. This
      quantitative and standardized way of assessing work-related disability is not
      sufficient to predict work ability and sick leave at the present time.

PMID- 16810566
TI  - Genetic and cultural transmission of smoking initiation: an extended twin kinship
      model.
AB  - BACKGROUND: Considerable evidence from twin and adoption studies indicates that
      genetic and shared environmental factors play a significant role in the
      initiation of smoking behavior. Although twin and adoption designs are powerful
      to detect genetic and environmental influences, they do not provide information
      on the processes of assortative mating and parent-offspring transmission and
      their contribution to the variability explained by genetic and/or environmental
      factors. METHODS: We examined the role of genetic and environmental factors for
      smoking initiation using an extended kinship design. This design allows the
      simultaneous testing of additive and non-additive genetic, shared and individual
      specific environmental factors, as well as sex differences in the expression of
      genes and environment in the presence of assortative mating and combined genetic
      and cultural transmission. A dichotomous lifetime smoking measure was obtained
      from twins and relatives in the Virginia 30,000 sample. RESULTS: Results
      demonstrate that both genetic and environmental factors play a significant role
      in the liability to smoking initiation. Major influences on individual
      differences appeared to be additive genetic and unique environmental effects,
      with smaller contributions from assortative mating, shared sibling environment,
      twin environment, cultural transmission and resulting genotype-environment
      covariance. The finding of negative cultural transmission without dominance led
      us to investigate more closely two possible mechanisms for the lower parent
      offspring correlations compared to the sibling and DZ twin correlations in
      subsets of the data: (i) age x gene interaction, and (ii) social homogamy.
      Neither mechanism provided a significantly better explanation of the data,
      although age regression was significant. CONCLUSIONS: This study showed
      significant heritability, partly due to assortment, and significant effects of
      primarily non-parental shared environment on smoking initiation.

PMID- 16810567
TI  - A multilevel analysis of key forms of community- and individual-level social
      capital as predictors of self-rated health in the United States.
AB  - Communities may be rich or poor in a variety of stocks of social capital. Studies
      that have investigated relations among these forms and their simultaneous and
      combined health effects are sparse. Using data on a sample of 24,835 adults (more
      than half of whom resided in core urban areas) nested within 40 U.S. communities
      from the Social Capital Benchmark Survey, correlational and factor analyses were
      applied to determine appropriate groupings among eight key social capital
      indicators (social trust, informal social interactions, formal group involvement,
      religious group involvement, giving and volunteering, diversity of friendship
      networks, electoral political participation, and non-electoral political
      participation) at each of the community and individual levels. Multilevel
      logistic regression models were estimated to analyze the associations between the
      grouped social capital forms and individual self-rated health. Adjusting the
      three identified community-level social capital groupings/scales for one another
      and community- and individual-level sociodemographic and socioeconomic
      characteristics, each of the odds ratios of fair/poor health associated with
      living in a community one standard deviation higher in the respective social
      capital form was modestly below one. Being high on all three (vs. none of the)
      scales was significantly associated with 18% lower odds of fair/poor health (odds
      ratio = 0.82, 95% confidence interval = 0.69-0.98). Adding individual-level
      social capital variables to the model attenuated two of the three community-level
      social capital associations, with a few of the former characteristics appearing
      to be moderately significantly protective of health. We further observed several
      significant interactions between community-level social capital and one's
      proximity to core urban areas, individual-level race/ethnicity, gender, and
      social capital. Overall, our results suggest primarily beneficial yet modest
      health effects of key summary forms of community social capital, and
      heterogeneity in some of these effects by urban context and population subgroup.

PMID- 16810568
TI  - Caloric restriction and human longevity: what can we learn from the Okinawans?
AB  - Caloric (or dietary) restriction (CR) extends lifespan and lowers risk for age
      associated diseases in a phylogenetically diverse group of species. Whether
      prolonged CR increases average or maximum lifespan or promotes a more youthful
      physiology in humans at advanced ages is not yet known. However, available
      epidemiological evidence indicates that CR may already have contributed to an
      extension of average and maximum life span in one human population and appears to
      have lowered risk for age associated chronic diseases in other human populations.
      We review the human studies in the context of a special human population, older
      Okinawans, who appear to have undergone a mild form of prolonged CR for about
      half their adult lives.

PMID- 16810570
TI  - Prevention of contrast agent-induced renal impairment in patients with chronic
      renal insufficiency and heart disease by high-dose intravenous N-acetylcysteine:
      a pilot-ministudy.
AB  - BACKGROUND: Contrast-induced nephropathy is a relatively common complication
      occurring after various procedures requiring contrast agent injection, especially
      in patients with pre-existing renal failure. AIM: This pilot study was designed
      to assess the effects of a high intravenous dose of N-acetylcysteine (NAC) on
      plasma creatinine concentration. METHODS: Twenty patients with pre-existing renal
      insufficiency were given NAC at a dose of 100 mg/kg. No contrast agent was given
      to 10 patients (Group A), whereas 10 patients received contrast at the time of
      coronary angiography (Group B). Changes in plasma creatinine were assessed at 3
      hours and one day following NAC administration. RESULTS: In Group B, NAC
      prevented creatinine increase: baseline levels were 210.98+/-77.33 micromol/L,
      200.26+/-71.94 micromol/L (NS) after 3 hours, and 203.80+/-83.94 micromol/L 24
      hours later (NS). The following was seen in Group A patients: 201.21+/-42.28
      micromol/L, 190.31+/-42.74 micromol/L (p<0.01), and 170.08+/-45.53 micromol/L
      (p<0.01), respectively. CONCLUSION: The results of this study confirm the
      effectiveness of NAC in prevention of contrast agent-induced renal impairment. In
      addition, we demonstrated the beneficial effects of NAC on renal function in
      patients who were not exposed to contrast agent. This pilot study should provide
      the basis for more comprehensive research and, also, for safe clinical practice.

PMID- 16810569
TI  - Dynamic visual acuity during passive head thrusts in canal planes.
AB  - We sought to determine whether the dynamic visual acuity (DVA) test, which has
      been used to measure the function of the two horizontal semicircular canals
      (SCCs), could be adapted to measure the individual function of all six SCCs using
      transient, rapid, unpredictable head rotation stimuli (head thrusts) in the
      direction of maximum sensitivity of each SCC. We examined head-thrust DVA (htDVA)
      performance in 19 healthy control subjects, five patients before and six patients
      after plugging of one superior SCC for treatment of superior canal dehiscence,
      and two subjects with unilateral vestibular deafferentation (UVD) by vestibular
      neurectomy. We compared htDVA results for each SCC to vestibulo-ocular reflex
      gains measured using 3-D scleral coil recordings during a passive head-thrust
      test paradigm. Individuals with normal vestibular function had similar htDVA
      scores for each of the six directions (canals) tested (mean 0.058 +/- 0.050
      LogMAR). Individuals tested after surgical plugging of one superior SCC were
      similar to normal for all SCCs except the plugged SCC, which had significantly
      worse htDVA scores (mean 0.270 +/- 0.08 LogMAR). Individuals with UVD had
      significantly worse htDVA scores for head rotations maximally exciting any of the
      ipsilesional SCC (mean 0.317 +/- 0.129 LogMAR) and scores similar to normal
      subjects for contralesional rotations (0.063 +/- 0.051 LogMAR). These findings
      suggest that the htDVA test, which does not require scleral coil placement,
      magnetic field coils, or expensive oculography equipment, can provide a useful
      quantitative measure of individual SCC function.

PMID- 16810572
TI  - Use of the LocaLisa mapping system during ablation procedures in patients with
      atrioventricular nodal reentrant tachycardia.
AB  - INTRODUCTION: LocaLisa is a novel system for anatomical mapping. It enables an
      assessment of the three-dimensional position of electrodes within cardiac
      chambers without fluoroscopy. With this technique it may be possible to reduce
      radiation exposure during catheter-based ablation procedures. AIM: To evaluate
      the efficacy and safety of ablation procedures performed using the LocaLisa
      mapping system in patients with atrioventricular nodal reentrant tachycardia
      (AVNRT). METHODOLOGY: This study evaluated the course of the first 26 ablations
      performed using the LocaLisa system (studied group). The control group involved
      30 consecutive patients with AVNRT treated with the conventional ablation
      technique that was routinely used prior to the introduction of the novel system
      into clinical practice. RESULTS: In the studied group procedural duration was
      72.4+/-24.9 minutes, in the control group 80.1+/-18.2 minutes (NS). However,
      radiation exposure was significantly lower in the examined group -- 74.4+/-109.2
      mGy compared to 184.8+/-59.9 mGy in the control group (p <0.05). All procedures
      were successful. No complications related to the ablation were observed.
      CONCLUSIONS: Employment of the LocaLisa mapping system enables the reduction of
      fluoroscopic exposure without any decrease of efficacy or elevation of risk of
      any complications during AVNRT ablations.

PMID- 16810573
TI  - Risk factors of atherosclerosis in premenopausal women with a sense of well
      being. A pilot study.
AB  - INTRODUCTION: Women before menopause are thought to be relatively safe from
      cardiovascular disease due to the protective effects of oestrogens, although one
      may question this opinion with regards to women with many typical risk factors.
      However, because of the shortage of data concerning prevalence of risk factors in
      young women, it is not known whether this phenomenon is confined to a limited
      group or affects many women. AIM: The purpose of this study was to determine the
      prevalence of either typical risk factors of atherosclerosis or emotional
      disturbances that might increase the probability of coronary artery disease in
      young women. METHODS: The study group involved 62 premenopausal women with a
      sense of well-being (regular menstruations, activity of serum follicle
      stimulating hormone < 15 IU/L). Mean age of women was 43.5 years. Total
      cholesterol, LDL and HDL fractions, triglyceride, lipoprotein (a) and
      homocysteine concentrations were examined and body mass index was calculated. A
      psychological examination assessing depression and neuroticism intensity was also
      performed. RESULTS: Total cholesterol concentration (mean values +/- SD,
      expressed as mg%, percentage of abnormal results are given in brackets) was
      206.3+/-35.8 (67.2), LDL cholesterol 124.3+/-30.2 (55.1), HDL cholesterol HDL
      62.5+/-14.8 (6.9), triglyceride 101+/-60.1 (13.8), lipoprotein (a) 18.9+/-17.5
      (44.8). Body mass index was 25.2+/-4.1 (41.3). History of smoking was positive in
      27.4% and 6.5% of examined women had arterial hypertension. Coexistence of 4 to 5
      aforementioned risk factors was noted in 27.4% of studied subjects. Mean
      homocysteine concentration was 10.7+/-2.1 micromol/L, while 41.3% of subjects had
      levels above the threshold of 11 micromol/l, commonly considered pathological.
      Symptoms of depression and neuroticism were seen in 30.5% and 22.5% of women,
      respectively. CONCLUSIONS: This pilot study of young women demonstrated that, in
      contrary to popular belief, this population is vulnerable to cardiovascular
      disease due to high prevalence of many risk factors.

PMID- 16810575
TI  - Inferior wall myocardial infarction with or without right ventricular involvement
      -treatment and in-hospital course.
AB  - INTRODUCTION: Right ventricular infarction (RVI) is most commonly associated with
      inferior wall infarction (20-50% of cases). Clinical presentation of RVI may
      vary. AIM: Assessment of outcome and clinical course of myocardial infarction in
      patients with inferior wall myocardial infarction with or without RVI.
      Additionally, risk stratification was attempted in the above-mentioned groups of
      patients. METHODS: The analysis involved 181 consecutive patients (pts) with
      inferior wall myocardial infarction hospitalised between 1 July 2000 and 1 July
      2002. RESULTS: Nineteen in-hospital deaths were noted in the study group
      (mortality 10.5%), reinfarction occurred in 6 (3.3%) pts, ischaemic stroke in 1
      (0.6%) patient, and 2 (1.1%) pts had transient ischaemic attack. Cardiogenic
      shock occurred in 20 (11.0%) pts , ventricular fibrillation in 15 (8.3%) pts, and
      pulmonary oedema in 9 (4.9%) pts. In the subgroup of 161 pts without cardiogenic
      shock 8 (4.9%) pts died. Thrombolytic therapy was administered in 96 (53%)
      subjects. Isolated inferior wall myocardial infarction was diagnosed in 94
      (51.9%) of 181 pts and RVI in 65 (35.9%) pts. Mortality rate in the RVI group was
      significantly higher than in inferior wall myocardial infarction without RVI and
      was 18.5% vs 2.12% (p=0.0003), respectively (excluding patients with cardiogenic
      shock: 11.1% vs 1.2%, respectively; p=0.016). In patients with RVI aged above 70
      years, the mortality rate was significantly higher than in younger patients (32%
      vs 10%, p=0.002). In a subgroup with RVI treated with thrombolysis mortality was
      considerably higher in subjects aged >70 years compared to patients below 70
      years (38.5% vs 7.7%, p=0.017). CONCLUSIONS: RVI is associated with worse
      prognosis and increased number of in-hospital complications. Older patients aged
      >70 years have definitely poorer prognosis. Thrombolytic therapy in a subgroup of
      older patients with RVI remains ineffective.

PMID- 16810577
TI  - Treatment of acute ST-segment elevation myocardial infarction in West Pomerania
      province of Poland. Comparison between primary coronary intervention and
      thrombolytic therapy.
AB  - INTRODUCTION: The majority of randomised studies on reperfusion in acute ST
      segment elevation myocardial infarction (STEMI) show the advantage of primary
      percutaneous coronary intervention (PCI) over thrombolysis. However, the real
      world registers' data are not so unequivocal. AIM: To evaluate the way acute
      STEMI is treated in West Pomerania province with emphasis on comparison of two
      reperfusion strategies, primary PCI vs thrombolytic therapy, in early and long
      term perspective. METHODS: Medical records of 961 STEMI patients treated between
      1 January 2003 and 31 December 2003 were analysed. Data were collected from 3
      centres with emergency cath lab availability and 15 regional sites. Long-term
      mortality was assessed based on regional provincial office database data.
      RESULTS: 69.9% of the study group received reperfusion (44.6% primary PCI, 25.3%
      thrombolysis). Mean age of patients was 62 (21 to 91) years. Patients referred
      for PCI were younger compared to the thrombolysis group. The percentage of
      females was similar in both groups. The majority of patients treated with PCI or
      thrombolysis were admitted to the hospital between 2 and 6 hours after symptoms-
      268 patients (46.4%). Seventy-nine patients (8.3%) died in the early (30-day)
      period. Mean age at time of death was 73 +/-8 years, whereas survivors' age was
      61.5 (+/-12) years (p <0.001). Significantly higher mortality was observed in the
      conservative treatment group (12.7%) compared to patients treated with
      reperfusion. Forty-two out of 662 patients treated with PCI and thrombolysis
      died. The group of thrombolytic therapy tended to have higher mortality (7.9%)
      than PCI patients (5.5%); the difference however was not significant. Early
      mortality was influenced by older age (73.4 vs 59.5), female gender, low ejection
      fraction, and previous myocardial infarction. Current smoking has a positive
      effect on survival (mortality rate in smokers was 2.6%, in non-smokers 8.2%;
      p=0.0001). In long-term follow-up overall mortality in the entire group of 961
      patients was 15.7% (12.1% in the reperfusion group). Long-term prognosis was
      worsened by older age, low ejection fraction, diabetes mellitus and non-smoking.
      CONCLUSIONS: Treatment of STEMI in West Pomerania province is similar to that
      used in Europe and the USA. No significant difference in 30-day and long-term
      mortality between the two types of reperfusion were seen.

PMID- 16810579
TI  - Efficacy of tilt training in patients with vasovagal syncope.
AB  - BACKGROUND: Besides pharmacological therapy and pacemaker implantation, tilt
      training is a promising method of treatment in patients with vasovagal syncope
      (VVS). Tilt training is usually offered to patients with malignant or recurrent
      VVS which impairs their quality of life and carries a risk of injury. AIM: To
      assess the efficacy of tilt training in patients with VVS. METHODS: The study
      group consisted of 40 patients (29 females, 11 males, aged 36.6+/-14 years, range
      18-57 years) who underwent tilt training using tilt table testing according to
      the Westminster protocol. The mean number of syncopal episodes prior to the
      initiation of tilt training was 6.5+/-4.9 (range 0-20); 3 patients had a history
      of very frequent faints. According to the VASIS classification, type I VVS
      (mixed) was diagnosed in 17 patients, type II (cardioinhibitory) in 22 subjects,
      and type III (vasodepressive) in one patient. Mean follow-up duration was 35.1+/
      13.5 months. The control group, which did not undergo the tilt testing programme,
      consisted of 29 patients with VVS (25 females, 4 males, mean age 44.2+/-15.0
      years) who had a mean of 3.3+/-3.2 (range 0-12) syncopal episodes in the past (p
      <0.05 vs study group); 6 of these patients had only pre-syncopal episodes. Type I
      VVS was diagnosed in 23 controls and type II VVS in 6 control subjects (syncope
      occurred during the passive phase of tilt testing in 7 subjects, whereas the
      remaining 22 fainted during NTG infusion). RESULTS: Of the patients from the
      study group, 3 underwent pacemaker implantation at the time of the initiation of
      tilt training. At the end of follow-up, 31 (77.5%) patients remained free from
      syncope recurrences, 5 had syncopal episodes during the initial phase of tilt
      training, whereas the remaining 4 continued to suffer from syncopal episodes. Out
      of 3 patients with presyncope, 2 had no syncope recurrences whereas 1 patient
      continued to have presyncopal attacks. Out of 3 patients with pacemakers, 1
      reported activation of pacing in the interventional mode. During the follow-up
      period, in 5 patients from the study group the diagnosis of VVS was not confirmed
      and another condition was diagnosed. In the control group, syncope recurrences
      occurred in 13 (44.5%) patients (p <0.05 vs study group). CONCLUSIONS: In
      patients with VVS, tilt training is effective in the majority of patients.
      Syncopal or presyncopal episodes and positive results of tilt testing take place
      more frequently in the early rather than in the late phase of training. Cessation
      of tilt training causes a recurrence of positive results of tilt testing in spite
      of the lack of spontaneous syncopal episodes. During long-term observation, a
      proper diagnosis, different from VVS, can be established in some patients.

PMID- 16810580
TI  - [Aorto-right ventricular fistula associated with aortic valve endocarditis: a
      case report].
AB  - A case of a 42-year old man with aortic valve endocarditis with peri-anular multi
      chamber abscess formation and fistulous communication between right sinus of
      Valsalva and right ventricle, is presented. Transthoracic echocardiography
      revealed abnormal flow through the fistula confirmed at surgery. Intraoperatively
      the aortic valve was severely damaged with massive calcifications on the
      leaflets, anulus, right sinus of Valsalva and interventricular septum surrounded
      by fresh vegetations. Surgical procedure consisted of removal of calcification
      and infected tissues, followed by reconstruction of interventricular septum and
      aorta with pericardial patch and aortic valve replacement. Postoperative course
      was uneventful.

PMID- 16810581
TI  - [Left ventricular free wall rupture complicating acute myocardial infarction
      treated surgically with patch glue repair of left ventricle: a case report].
AB  - The case of a 73-year-old female with an acute myocardial infarction, treated
      successfully with primary percutaneous coronary intervention who developed
      subacute left ventricular free wall rupture, is presented. The diagnosis was
      established by echocardiography at bedside. She underwent urgent cardiac surgery
      with patch glue repair of left ventricular free wall rupture and selective
      revascularisation. The recovery was uneventful and the patient was discharged
      from the hospital on the 11th postoperative day in good condition. At 6 month
      follow-up, the patient remained well, without any symptoms.

PMID- 16810582
TI  - [Haemolytic anaemia following implantation of the mitral annuloplasty ring: a
      case report].
AB  - Haemolytic anaemia following mitral annuloplasty is uncommon as compared with
      mitral valve replacement procedures. A 67-year-old woman, who underwent mitral
      annuloplasty and CABG, developed haemolytic anaemia. Echocardiographic
      examination revealed mitral regurgitation jet colliding with mitral ring. The
      management of these cases usually demands redo surgery. In the presented case,
      the direction of mild mitral regurgitant jet with respectfully high velocity
      contributed significantly to the early postoperative haemolysis. Redo surgery
      with implantation of bioprosthesis caused withdrawal of intravascular haemolysis.

PMID- 16810583
TI  - [Complete heart block due to Wegener's granulomatosis: a case report and
      literature review].
AB  - Involvement of the conduction system of the heart in Wegener's granulomatosis
      (WG) is rare. We present a 53-year-old man with WG pulmonary, renal and left
      eyeball involvement and with a high initial level of cANCA (1: 640). He was
      treated with steroids, cyclophosphamide and cyclosporine. After 14 months he
      presented with lethargy and presyncope due to a complete atrio-ventricular block
      with an escape rhythm of 35 beats/min. The temporary pacing electrode was
      inserted, followed by permanent DDDR pacemaker implantation on the third day as
      the block persisted despite WG treatment intensification. Clinical picture showed
      the disease in a progressive state.

PMID- 16810585
TI  - [Partial papillary muscle ruptures complicating acute myocardial infarctions.
      Diagnosis by transesophageal echocardiography].
AB  - Partial papillary muscle rupture is a rare but fatal mechanical complication of
      acute myocardial infarction. Survival depends on prompt recognition and immediate
      medical and surgical therapy. The partial rupture of an anterolateral papillary
      muscle was clearly diagnosed by transgastric two-chamber view during TEE in a 64
      year-old man who suffered from acute myocardial infarction.

PMID- 16810584
TI  - [Gender-related differences in the course of ischaemic heart disease in women].
AB  - Two cases of menopausal age women with acute coronary syndromes are presented.
      Clinical symptoms and diagnostic tests were similar for women and for men. Gender
      differences in angiographic lesion pathophysiology were found. The substrate for
      thrombosis in women was probably plaque erosion.

PMID- 16810586
TI  - [Patient with pacemaker. What is the underlying, intrinsic cardiac rhythm?].

PMID- 16810587
TI  - [Pancreas and kidney transplantation complicated by acute coronary syndrome].

PMID- 16810588
TI  - [QRS and cycle length alternans during atrioventricular nodal reentry
      tachycardia: case report].
AB  - A 23-year old man with paroxysmal, poorly tolerated and spontaneously terminating
      palpitations, was referred to our department for electrophysiological study.
      Burst pacing from high right atrium using a cycle length of 350 ms induced a
      slowfast atrioventricular nodal reentry tachycardia. We excluded the presence of
      accessory atrioventricular tracts. During tachycardia a constant alternans of QRS
      morphology and cycle length was observed. The cycle length alternans could be due
      to the presence of three nodal pathways and activation circulating in a figure-of
      eight pattern using alternatively two slow pathways as the antegrade arm of the
      reentry loop. The alternans could also originate from altering decremental
      properties of a single slow pathway that changed its conduction properties with
      relation to the length of the preceding cycle. The QRS alternans occurred both
      during burst pacing and tachycardia. As it was related to the rate and the
      changing cycle length, we concluded that it could reflect aberration in
      intraventricular conduction.

PMID- 16810589
TI  - [Angiotensin II-receptor antagonists for the treatment of prehypertension.
      Results of the randomised prospective TROPHY trial].

PMID- 16810590
TI  - [Stem cells--hope or myth?].

PMID- 16810591
TI  - Risk factors for pancreatitis after pancreatic sphincterotomy: a review of 572
      cases.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic pancreatic sphincterotomy is indispensable
      for many therapeutic endoscopic maneuvers, but is also associated with a higher
      risk of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).
      In this study, this subgroup of patients was investigated in order to identify
      risk factors and protective factors. PATIENTS AND METHODS: A retrospective chart
      review identified 572 endoscopic pancreatic sphincterotomies that met the
      inclusion criteria. Charts were examined for indications, endoscopic technique,
      and outcomes, including pancreatitis. RESULTS: A total of 477 patients underwent
      572 endoscopic pancreatic sphincterotomies during a 5-year period. Indications
      for sphincterotomy included chronic pancreatitis (n = 398), access for tissue
      sampling (n = 52), acute recurrent pancreatitis (n = 45), transpapillary drainage
      of a pancreatic pseudocyst (n = 32), precut access to the common bile duct (n =
      29), and others (n = 16). Pancreatic duct drainage was performed in 69.1 % of the
      procedures (nasopancreatic catheter, n = 290, or pancreatic stent placement, n =
      105). Post-ERCP pancreatitis occurred in 69 cases (12.1 %) and was severe in 10.
      The multivariate analysis identified female sex as being associated with a higher
      risk of pancreatitis, while an elevated C-reactive protein level, pancreatic
      ductal stones, sphincterotomy at only the major papilla, and pancreatic duct
      drainage with a nasopancreatic catheter or stent were associated with a lower
      risk. CONCLUSIONS: This large series of patients undergoing endoscopic pancreatic
      sphincterotomy provides further evidence that both patient characteristics and
      technical factors modify the risk profile for post-ERCP pancreatitis. In addition
      to providing further definition of which patients are at risk, it also suggests
      that pancreatic duct drainage is an independently significant protective
      maneuver.

PMID- 16810592
TI  - Quality of psychomotor recovery after propofol sedation for routine endoscopy: a
      randomized and controlled study.
AB  - BACKGROUND AND STUDY AIMS: Propofol sedation is increasingly being used for
      endoscopy in the outpatient setting. In view of the agent's short period of
      action, current recommendations that patients should avoid driving or using
      public transport unescorted for 24 h may be too strict. Psychomotor recovery and
      driving skills before and after sedation were therefore assessed. PATIENTS AND
      METHODS: A total of 100 patients undergoing routine upper or lower
      gastrointestinal endoscopy were randomly sedated either with propofol alone or
      with midazolam plus pethidine. The recovery time and quality of recovery were
      assessed. Psychomotor recovery was evaluated using the number connection test
      (NCT) and a driving simulator test 1 h before and 2 h after the endoscopic
      procedure. RESULTS: Ninety-six patients completed the 2-hour post-sedation
      procedure. Vital signs were recorded, and no clinically relevant complications
      occurred. The mean recovery time and quality of recovery were significantly
      better after propofol sedation (14 +/- 9 min vs. 25 +/- 8 min and 8.7 +/- 1.3 vs.
      6.3 +/- 1.1 points) ( P < 0.01). Psychomotor and driving skills after propofol
      sedation were similar to the baseline results, while in the midazolam/pethidine
      group, patients showed significantly more lane deviations (1.1 +/- 0.9 vs. 1.6 +/
      0.9), time over the speed limit (0.3 +/- 0.83 vs. 0.6 +/- 0.88), missed
      stoplights more often (0.05 +/- 0.31 vs. 0.11 +/- 0.35), and had slower reaction
      times for unexpected events (1.11 +/- 0.46 s vs. 1.39 +/- 0.44 s) ( P < 0.01).
      The time needed to complete the NCT after sedation did not differ between the two
      groups (32.1 +/- 12.0 s vs. 33.4 +/- 12.6 s for propofol; 31.5 +/- 11.2 s vs.
      34.6 +/- 12.8 s for midazolam/pethidine). CONCLUSIONS: Current recommendations
      that patients should refrain from driving and unescorted use of public transport
      for 24 h after sedation may need to be reconsidered in patients who receive
      propofol sedation.

PMID- 16810593
TI  - Endoscopic and histological findings in the duodenum of adults with celiac
      disease before and after changing to a gluten-free diet: a 2-year prospective
      study.
AB  - BACKGROUND AND STUDY AIMS: Published follow-up data on small-intestinal recovery
      in patients with celiac disease are scarce and contradictory. This is especially
      the case for adult patients, who often show incomplete histological recovery
      after starting a gluten-free diet (GFD). We conducted a 2-year prospective study
      to evaluate the effectiveness of a GFD in improving the endoscopic and
      histological duodenal findings in adults with celiac disease. PATIENTS AND
      METHODS: We studied 42 consecutive adults with newly diagnosed celiac disease (13
      men, 29 women; mean age 32.7 years, range 15 - 72 years). All the patients
      underwent esophagogastroduodenoscopy and small-bowel biopsy. We devised our own
      grading system for the endoscopic appearance of the duodenum, which ranged from
      "normal" appearance to "mild", "moderate", or "severe" alterations. Small-bowel
      biopsies were obtained from the second part of the duodenum (and from the
      duodenal bulb when it had a micronodular appearance). The histopathological
      appearances were described according to modified Marsh criteria. RESULTS: A
      normal endoscopic appearance in the duodenum was found in 5/42 patients (11.9 %)
      at entry and in 32/42 patients (76.2 %) after 2 years on a GFD. Subdividing the
      patients according to age, patients aged from 15 years to 60 years showed
      significant improvement within 12 months ( P < 0.0001 for patients aged from 15
      years to 45 years; P < 0.003 for patients in the 46 years to 60 years group),
      whereas the improvement in endoscopic findings in patients older than 60 years
      was not statistically significant, even 24 months after starting the GFD.
      "Normal" histology was reported in none of the patients at entry, but in 25
      patients (59.5 %) after 24 months on a GFD, but this parameter did not show a
      significant improvement until the patients had been on the GFD for 12 months ( P
      < 0.0001). Only the younger patients (5 - 30 years) showed significant
      improvement of histology within 12 months ( P < 0.034); older patients (>30
      years) showed histological improvement but this was not statistically
      significant, even after 24 months on a GFD. CONCLUSIONS: This study shows for the
      first time that endoscopic recovery is faster than histological recovery in
      adults with celiac disease who go on a GFD. Moreover, older patients showed
      incomplete endoscopic and histological recovery even 24 months after starting a
      GFD. We therefore advise, as a minimum recommendation, that follow-up biopsies
      should be taken 1 - 2 years after starting a GFD in adults with celiac disease.

PMID- 16810594
TI  - Multicenter comparative trial of the V-scope system for therapeutic ERCP.
AB  - BACKGROUND AND STUDY AIMS: A new duodenoscope (the V-scope), with a modified
      elevator used in combination with a dedicated short guide wire, constitutes the V
      system. This system is intended to allow fixation of the guide wire at the
      elevator lever, thereby enhancing the speed and reliability of accessory exchange
      over a guide wire during ERCP. The aim of this study was to evaluate the extent
      to which the V-system provides improved efficiency in comparison with
      conventional duodenoscope and guide wire combinations. PATIENTS AND METHODS: This
      was an industry-sponsored multicenter randomized trial. Patients undergoing
      endoscopic retrograde cholangiopancreatography (ERCP) procedures in which
      treatment was anticipated were randomly assigned to the V-system or to a
      conventional duodenoscope and accessories used routinely in each center. The
      parameters recorded included the total case time, fluoroscopy time,
      catheter/guide wire exchange time, guide wire repositioning, loss of guide wire
      access, and success or failure of guide wire fixation when using the V-system.
      RESULTS: Fifty patients were included, 22 in the conventional group and 28 in the
      V-system group. A total of 135 exchanges were carried out. The patients had up to
      six exchanges. The median exchange time was 19.4 s with the V-system and 31.7 s
      with the conventional systems ( P < 0.001). Guide wire repositioning was required
      less often in the V-system group ( P = 0.0005). The V-system effectively locked
      the guide wire in 63 of 71 exchanges (89 %). Loss of guide wire access occurred
      in two patients in the conventional group and four in the V-system group,
      attributable to failure to lock the guide wire early during the experience (no
      significant differences). CONCLUSIONS: The V-system can effectively secure the
      guide wire during accessory exchange in ERCP and reduces the time required to
      exchange accessories. This may enhance overall efficiency during ERCP.

PMID- 16810595
TI  - Intraductal ultrasonography in the diagnosis of Mirizzi syndrome.
AB  - BACKGROUND AND STUDY AIMS: Common bile duct (CBD) compression can be caused by
      stones in the cystic duct (Mirizzi syndrome) which can be difficult to diagnose
      even with endoscopic retrograde cholangiopancreatography (ERCP). Conventional
      imaging often gives insufficient information and endoscopic ultrasonography (EUS)
      and magnetic resonance imaging may improve diagnostic accuracy, but often the
      final diagnosis is made during exploratory surgery. PATIENTS AND METHODS: All
      patients undergoing ERCP during a 3-year period were prospectively analyzed if
      they fulfilled the inclusion criteria: gallbladder in situ; obstructive jaundice
      with CBD stenosis, demonstrated at endoscopic retrograde cholangiography (ERC),
      but unexplained at ultrasonography; and inability to demonstrate the cystic duct
      during ERC. Intraductal ultrasonography (IDUS) was carried out over a guide wire
      using a 20-MHz probe. Prior to ERCP, patients were evaluated with abdominal
      ultrasonography and computed tomography (CT), as well as by magnetic resonance
      cholangiopancreatography (MRCP) or EUS in some. RESULTS: 74 patients out of 2089
      undergoing ERCP fulfilled the entry criteria. Final diagnoses, from surgical
      exploration (n = 41), cytology (n = 21), or endoscopic extraction of stones from
      the cystic duct (n = 12), were Mirizzi syndrome (type I) in 30 patients and other
      causes in 44 patients (gallbladder carcinoma [n = 16], pancreatic carcinoma [n =
      9], metastatic compression [n = 9], other [n = 10]). CT had shown suspected
      Mirizzi syndrome in 1/30 cases (3 %) and MRCP in 12/19 evaluated cases (63 %).
      EUS allowed a correct diagnosis in 11 of 15 evaluated cases (73 %). IDUS required
      an additional 8 +/- 3 min and showed a sensitivity of 97 % and specificity of 100
      %. CONCLUSION: IDUS is a sensitive and specific method for the diagnosis of
      Mirizzi syndrome.

PMID- 16810596
TI  - Magnetic loop basket: a "two-in-one" instrument.
AB  - BACKGROUND AND STUDY AIMS: Ingested coins are the most common foreign bodies
      encountered in the upper gastrointestinal tract in India and if they remain in
      the stomach for more than 5 days they need to be removed. Ferromagnetic retrieval
      instruments only work if the coins are ferromagnetic; and it is difficult to
      maneuver a loop basket in the fundus of the stomach. A magnetic loop basket was
      designed in an effort to overcome these difficulties and we assessed its
      feasibility, safety, and effectiveness in the removal of coins from the fundus of
      the stomach. PATIENTS AND METHODS: Twenty patients with a history of ingested
      coins were scheduled for removal of the coins using the magnetic loop basket. The
      time taken, complications, and failure rates were recorded. RESULTS: Twelve
      ferromagnetic coins were removed in a mean time of 60 seconds (range 30 - 90
      seconds) and eight non-ferromagnetic coins were removed in a mean time of 150
      seconds (range 90 - 180 seconds) without any failures or complications.
      CONCLUSION: The magnetic loop basket is a safe, effective, and quick method for
      removing both ferromagnetic and non-ferromagnetic metallic coins.

PMID- 16810597
TI  - Predictors of peptic ulcer rebleeding after scheduled second endoscopy: clinical
      or endoscopic factors?
AB  - BACKGROUND AND STUDY AIMS: In a previous study we demonstrated the efficacy of
      second-look endoscopy with therapy within 16 - 24 hours after index endoscopy in
      reducing major recurrent peptic ulcer bleeding. In this study, we sought to
      identify factors that might predict further rebleeding after this scheduled
      second-look endoscopy. PATIENTS AND METHODS: We studied 249 patients (181 men, 68
      women) with acute bleeding peptic ulcers who were treated at the United Christian
      Hospital, Hong Kong from 1999 to 2002 and who underwent a scheduled second
      endoscopy. Those patients who developed rebleeding after the second endoscopy
      were evaluated, and possible predictive factors for rebleeding were analyzed
      using a logistic regression model. RESULTS: Of the 249 patients who underwent
      scheduled second-look endoscopy, 17 patients (6.8 %) developed rebleeding: seven
      of these patients were treated by another endoscopic therapy; ten patients
      required surgery. The overall mortality rate was 3.1 %. A logistic regression
      analysis performed on the possible predictive factors for rebleeding found that
      the following factors were associated with a significant risk of further
      rebleeding after scheduled second endoscopy: American Society of
      Anesthesiologists (ASA) grade III or grade IV status (odds ratio 3.81, 95 % CI
      1.27 - 11.44), ulcer size greater than 1.0 cm (odds ratio 4.69, 95 % CI 1.60 -
      13.80), and a finding of persistent stigmata of recent hemorrhage at the
      scheduled second endoscopy (odds ratio 6.65, 95 % CI 2.11 - 20.98). CONCLUSIONS:
      Endoscopic factors, including large ulcer size and the persistence of endoscopic
      stigmata of recent hemorrhage are important predictors for recurrent bleeding
      after scheduled second endoscopy.

PMID- 16810598
TI  - Primary sclerosing cholangitis and recognition of bile duct cancer: problem
      solved?

PMID- 16810599
TI  - Peritonitis after percutaneous endoscopic gastrostomy and jejunostomy: where
      there is smoke, there may not be fire.
AB  - Extensive reviews have been published regarding complications arising from
      percutaneous enteral access and ways of managing them. However, few data are
      available regarding unnecessary clinical interventions resulting from
      misinterpretation of benign postprocedural findings. We present here three
      representative cases of negative surgical abdominal cavity explorations for
      presumed peritonitis after percutaneous endoscopic gastrojejunostomy and
      jejunostomy.

PMID- 16810601
TI  - Patient position during ERCP: prone versus supine. What about left lateral
      throughout?

PMID- 16810602
TI  - Safety and efficacy of large-diameter esophageal metal stents.

PMID- 16810603
TI  - Minimum required resolution standard required for analysis of mucosal
      microvascular architecture at magnification endoscopy.

PMID- 16810605
TI  - Hyperphosphataemia after bowel preparation with oral sodium phosphate.

PMID- 16810606
TI  - Arterioesophageal fistula secondary to rupture of an aberrant right subclavian
      artery aneurysm: a rare differential diagnosis in upper gastrointestinal
      bleeding.

PMID- 16810607
TI  - Esophageal tumor diagnosed by capsule endoscopy.

PMID- 16810609
TI  - The 2001 World Health Organization and updated European clinical and pathological
      criteria for the diagnosis, classification, and staging of the Philadelphia
      chromosome-negative chronic myeloproliferative disorders.
AB  - The clinical criteria according to the Polycythemia Vera Study Group (PVSG) do
      not distinguish between essential thrombocythemia (ET), thrombocythemia
      associated with early-stage polycythemia vera (PV) and prefibrotic chronic
      idiopathic myelofibrosis (CIMF). The criteria only classify the advanced stage of
      PV with increased red cell mass. The classification of myeloproliferative
      disorders (MPDs), proposed by the World Health Organization (WHO) in 2001, is a
      compromise of the clinical PVSG and WHO bone marrow criteria, and excludes early
      stages of ET and PV. The updated European clinical and pathological criteria
      combine the WHO bone marrow criteria with established and new clinical,
      laboratory, biological, and molecular MPD markers. This allows clinicians and
      pathologists to diagnose early-stage MPD and to differentiate ET, PV, and
      prefibrotic chronic idiopathic myelofibrosis (CIMF). Depending on laboratory
      tests and diagnostic criteria used, the population of the MPD patients defined as
      ET, PV, and CIMF are heterogeneous at the clinical, laboratory, and biological
      and pathological levels. The recent discovery of the JAK2 V617F mutation, which
      is the cause of a distinct trilinear MPD in its manifold clinical manifestations
      during long-term follow-up, increases the specificity of a positive JAK2 V617F
      polymerase chain reaction (PCR) test for the diagnosis of MPD (near 100%), but
      only half of the ET and CIMF patients according to the PVSG (sensitivity 50%) and
      the majority of PV patients (sensitivity 95%) are JAK2 V617F positive. A
      comparison of the laboratory features of JAK2 V617-positive and JAK2 wild-type ET
      patients clearly showed that JAK2 V617-positive ET is characterized by higher
      values for hemoglobin, hematocrit, and neutrophil counts; lower values for serum
      erythropoietin (EPO) levels, serum ferritin, and mean corpuscular volume; and by
      increased cellularity of the bone marrow in biopsy material. This indicates that
      JAK2 V617-positive ET patients, diagnosed according to the PVSG criteria,
      represent a "forme fruste of PV" consistent with early PV mimicking ET (JAK2
      V617F trilinear MPD). In contrast, the JAK2 wild-type ET patients had
      significantly higher platelet counts and usually had a clinical picture of ET
      with normal serum EPO levels, PRV-1 expression, and leukocyte alkaline
      phosphatase score, and a typical WHO ET bone marrow picture. The clinical and
      pathological data on JAK2 V617F-positive MPD patients suggest that the JAK2 V617F
      mutation defines one disease entity with several sequential steps of ET, PV, and
      secondary myelofibrosis during long-term follow-up, and that the wild-type JAK2
      MPDs may represent another distinct entity with a related but different molecular
      etiology. MPD-specific markers such as serum EPO, endogenous erythroid colony
      formation (EEC), and JAK2 V617F have high specificities, but the sensitivities
      are not high enough to detect the early stages of the MPDs, ET, PV, and
      prefibrotic CIMF. Bone marrow histopathology in addition to clinical, laboratory,
      biological, and molecular markers, including the JAK2 V617 PCR test, serum EPO,
      PRV-1, EEC, LAP score, peripheral blood parameters, and spleen size on echogram
      will detect the early stages of MPD and allows diagnostic differentiation of the
      three primary MPDs (ET, PV, and CIMF) in both JAK2 V617F-positive and JAK2 wild
      type MPD patients.

PMID- 16810610
TI  - New insights into the pathogenesis of JAK2 V617F-positive myeloproliferative
      disorders and consequences for the management of patients.
AB  - The identification of the JAK2 V617F mutation in patients with myeloproliferative
      disorders (MPDs) represents a major breakthrough in our understanding of the
      pathogenesis of these diseases. One year after its discovery, an impressive
      number of publications appeared. These articles confirmed most of the initial
      results and tried to focus on the main issues arising from this discovery. JAK2
      V617F came as recognition of the work of many investigators, starting with
      William Dameshek, who demonstrated that classical MPDs shared phenotypical
      mimicry and a general pattern of clinical evolution. We now know that this
      mutation is the common mark of a molecular clinical entity of MPD shared by 90%
      of polycythemia vera (PV) and approximately 50% of essential thrombocythemia and
      idiopathic myelofibrosis patients. However, many questions arise from this
      discovery. This review, in view of the recent literature, tries to address
      crucial questions regarding the mechanism of action and the clinical relevance of
      the JAK2 V617F mutation. The first question is how a unique mutation may explain
      the clinical diversity of JAK2 V617F-positive MPDs. We now know that acquisition
      of this mutation is only one step, and that gain of the JAK2 V617F locus, as gain
      in constitutive Janus kinase 2 (JAK2) activity, may represent another step in
      disease progression. It is still not known if and how this event or other unknown
      events may favor disease diversity and possibly disease onset. The second
      question is how the identification of the JAK2 V617F mutation will change our
      approach to patients. If detection of JAK2 V617F drastically simplifies the
      diagnosis of MPDs, and especially PV, prospective clinical trials will be
      necessary to determine if the therapeutic attitude and disease prognosis will
      depend on the presence of JAK2 V617F. The third question is how this discovery
      will benefit the patients. The immediate benefits are still difficult to
      evaluate, but this discovery, as a major advance in our understanding of the
      pathogenesis of MPDs, surely has opened perspectives for possible targeted
      therapies and raises new hopes for patients and clinicians.

PMID- 16810611
TI  - Effects of anagrelide on megakaryopoiesis and platelet production.
AB  - Possible pathomechanisms regarding the thromboreductive effect of anagrelide
      (ANA) include decrease in the megakaryocyte cell mass or life span of platelets,
      interference with maturation, and stimulation of apoptosis and proliferation.
      Finally, a fibrogenic effect has been reported in patients with high-risk
      essential thrombocythemia (ET). Based on scrutinized evaluations, including
      immunohistochemistry and morphometry performed on representative bone marrow (BM)
      biopsies, ANA was found to exert a significant influence on the endoreduplicative
      activity of megakaryopoiesis, with an arrest of maturation at lower ploidy stages
      causing a predominance of precursors. This result confirms and greatly extends
      former investigations that also failed to document a decrease in quantity or
      enhancement of apoptosis. Moreover, a comparative study on the putative mutagenic
      capacity of hydroxyurea (HU) versus ANA treatment reveals that both agents
      generate a left-shifting of megakaryocytes. However, HU creates conspicuously
      expressed maturation defects consistent with dysplastic changes of
      megakaryopoiesis, and therefore supports concerns about the possible leukemogenic
      potential of this drug. On the other hand, in follow-up examinations of BM
      specimens, ANA failed to show a stimulation of myelofibrosis in ET, provided
      diagnosis was established according to the World Health Organization criteria.

PMID- 16810612
TI  - The impact of clinicopathological studies on staging and survival in essential
      thrombocythemia, chronic idiopathic myelofibrosis, and polycythemia rubra vera.
AB  - In chronic myeloproliferative disorders (MPDs), varying results regarding staging
      of disease and assessment of outcome have been reported. Risk classification is
      mainly based on clinical data; however, in those disorders associated with an
      elevated platelet count, discrimination of (true) essential thrombocythemia (ET)
      may be difficult without the possibility to recognize characteristic
      histopathological bone marrow patterns according to the World Health Organization
      (WHO) guidelines. Patients with ET reveal no relevant reduction of life
      expectancy and the impact of disease is significantly higher in elderly patients,
      especially in chronic idiopathic myelofibrosis (IMF) and polycythemia rubra vera
      (PV). In high-risk ET, the overall incidence of myelofibrotic transformation
      after 36 months of follow-up is 2.8% when considering the Polycythemia Vera Study
      Group guidelines. In contrast, classification according to WHO fails to show a
      relevant transformation into myelofibrosis either by clinical or morphological
      standards in (true) ET. Early stages of IMF show a more favorable outcome, but in
      multivariate risk classification, signs of myeloid metaplasia have the most
      important impact on prognosis. In PV, the risk for thrombosis increases with age,
      and furthermore, signs of generalization are generally associated with a
      worsening of prognosis. It has been shown that examination of bone marrow
      specimens enhances the diagnostic reliability and also enables the recognition of
      evolving myelofibrotic transformation in MPDs.

PMID- 16810613
TI  - Risk factors for thrombosis and bleeding and their influence on therapeutic
      decisions in patients with essential thrombocythemia.
AB  - The clinical course of essential thrombocythemia (ET) is variable, ranging from
      microvascular circulation disturbances to severe thromboembolic or hemorrhagic
      complications in patients who do not have any symptoms for many years. The
      identification of patients at risk for major thrombosis who need platelet
      lowering therapy is important. During the last two decades, several risk factors
      for the development of ET-related thrombotic and bleeding complications have been
      identified. These include platelet counts, previous thrombotic events, older age,
      cardiovascular risk factors, hereditary thrombophilia, clonality, and the
      presence of molecular markers such as PRV-1 or the Janus kinase 2 (JAK2)
      mutation. According to the presence or absence of these risk factors, individual
      patients with ET are currently stratified as low-, intermediate-, or high-risk
      patients. The influence of these risk factors on therapeutic decisions in
      patients with ET is critically reviewed and discussed in detail.

PMID- 16810614
TI  - The role of JAK2 V617F mutation, spontaneous erythropoiesis and
      megakaryocytopoiesis, hypersensitive platelets, activated leukocytes, and
      endothelial cells in the etiology of thrombotic manifestations in polycythemia
      vera and essential thrombocythemia.
AB  - Exaggerated erythropoiesis and megakaryocytopoiesis are present at a variable
      extent in polycythemia vera (PV) and essential thrombocythemia (ET). With the
      recent discovery of the V617F mutation in the Janus kinase 2 (JAK2) tyrosine
      kinase in almost all cases of PV and in a subset of patients with ET, studies are
      now pending to assess the role of this mutation in the hematopoietic cell
      activation process and/or in the occurrence of thromboses in ET and PV. The JAK2
      V617F point mutation makes the normal hematopoietic progenitor cells
      hypersensitive to thrombopoietin, erythropoietin, and myeloid progenitor cells,
      leading to trilinear hematopoietic myeloproliferation. This will have three main
      clinical consequences during long-term follow-up. First, spontaneous growth of
      enlarged mature megakaryocytes in ET/PV with overproduction of hypersensitive
      platelets results in a broad spectrum of platelet-mediated microvascular
      circulatory disturbances, which are very sensitive to low-dose aspirin. Second,
      spontaneous growth of erythropoiesis with the overproduction of erythrocytes
      leads to classic PV with increased hemoglobin, hematocrit, and red cell mass.
      This is associated with a high frequency of major arterial and venous thrombotic
      complications in addition to platelet-mediated microvascular circulatory
      disturbances of thrombocythemia. Third, the slowly progressive myeloid
      (granulocytic) metaplasia in bone marrow and spleen is complicated by secondary
      myelofibrosis caused by a megakaryocytic/granulocytic cytokine storm in about one
      fourth to one third of JAK2 V617F-positive PV patients after long-term follow-up,
      with no tendency of leukemic transformation as long as they are not treated with
      myelosuppressive agents. Randomized clinical trials directly comparing phlebotomy
      versus hydroxyurea or interferon alpha versus hydroxyurea in PV with progressive
      disease are lacking. Heterozygous V617F mutation is enough to produce the
      clinical picture of ET with a slight tendency to increased hemoglobin and
      hematocrit (early PV mimicking ET). Homozygous V617F mutation is associated with
      the clinical picture of classic PV and with a higher tendency to secondary
      myelofibrosis, but with no increased leukemia unless other biological or genetic
      factors come into play, such as myelosuppressive agents or the acquisition of
      additional biologic or genetic defects. Depending on the biological background of
      individual patients, heterozygous and homozygous JAK2 V617F ET/PV may
      preferentially induce myeloid metaplasia with myelofibrosis with a relative
      suppression of megakaryocytic and erythropoietic myeloproliferation leading to
      clinical pictures of fibrotic chronic idiopathic myelofibrosis (CIMF) or
      agnogenic myeloid metaplasia. The main conclusion is that JAK2 V617F is a 100%
      specific clue to a new distinct clonal myeloproliferative disorder. JAK2 V617F
      positive ET/PV and CIMF should be distinguished from wild-type JAK2 ET, rare
      cases of PV, and CIMF, and should be evaluated during life-long follow-up.

PMID- 16810615
TI  - Anagrelide: what was new in 2004 and 2005?
AB  - Anagrelide is an established platelet-reducing drug. Although there are gaps in
      the understanding of its mechanism of action, two randomized comparisons with
      other drugs used for therapy of patients with essential thrombocythemia (ET) have
      been performed. Recent progress has been made in this field with the development
      of better determination techniques, with the characterization of metabolites, and
      with studies of their mechanism of action on megakaryocytes and platelets. More
      data are now available from various noncomparative clinical trials on its
      clinical efficacy and safety. Only few investigations are available that document
      its long-term effects. Although the drug should not be used during pregnancy,
      there are a few studies that report that pregnant women have taken this drug
      without harm to the newborn. Studies have also investigated the effects of
      anagrelide on platelets, indicating that platelet function is as important as
      platelet counts in ET. Preliminary analyses of the mechanism of action of
      anagrelide have revealed that the drug interferes with the signal transduction of
      the thrombopoietin receptor. Results of the first phase III trial (PT1) that
      compared anagrelide/aspirin with hydroxyurea/aspirin have sparked an intense
      discussion, given that the combination of anagrelide and aspirin causes more
      bleeding complications in the gastrointestinal tract. It has been speculated that
      the higher number of transient ischemic attacks in this study arm is not caused
      by thrombotic events but by small bleedings that would be responsible for
      transient hemorrhagic attacks. More insights are expected from the recently
      completed ANAHYDRET trial that compared monotherapy with hydroxyurea and
      anagrelide.

PMID- 16810616
TI  - Pegylated interferon therapy for patients with Philadelphia chromosome-negative
      myeloproliferative disorders.
AB  - The conventional management of patients with high-risk Philadelphia chromosome
      negative (Ph-negative) myeloproliferative disorders (MPDs) revolves around the
      administration of cytoreductive agents such as hydroxyurea, anagrelide, and
      recombinant human interferon alpha (IFN-alpha). IFN-alpha has shown significant
      activity in the treatment of chronic myelogenous leukemia (CML) and Ph-negative
      MDPs. However, the response rates of IFN-alpha therapy frequently have been
      hampered by high dropout rates due to side effects and inconvenient dosing
      schedules. Pegylated (PEG) IFN-alpha is formulated by covalently attaching
      polymers of ethylene glycol of large molecular weight to the native IFN-alpha
      molecule. Such chemical modification increases serum half-life, decreases renal
      excretion, and results in prolonged patient exposure to PEG-IFN-alpha, thus
      allowing for weekly administration while maintaining acceptable toxicity,
      tolerability, and activity profiles. The lack of adequate therapies for patients
      with MPDs and the superior pharmacokinetic and pharmacodynamic profile of PEG-IFN
      alpha relative to standard IFN-alpha has prompted the investigation of the
      activity and safety of PEG-IFN-alpha in patients with essential thrombocythemia,
      polycythemia vera, and idiopathic myelofibrosis. We summarize the available data
      on the use of PEG-IFN-alpha in patients with Ph-negative MPDs.

PMID- 16810617
TI  - Long-term incidence of hematological evolution in three French prospective
      studies of hydroxyurea and pipobroman in polycythemia vera and essential
      thrombocythemia.
AB  - Despite recent discoveries made in myeloproliferative disorders other than
      chronic myelogenous leukemia, which it is hoped will result in earlier diagnosis,
      and better evaluation and management of patients, hematological evolution to
      myelofibrosis, acute leukemia, and myelodysplastic syndromes (AL/MDS) remain
      major causes of long-term mortality in polycythemia vera (PV) and essential
      thrombocythemia (ET) patients. Evaluation of long-term leukemogenic risk of
      currently available drugs, therefore, is crucial. We report updated results of
      three French prospective trials of hydroxyurea and pipobroman in PV and ET
      patients with a median follow-up longer than 10 years. The results show that the
      incidence of AL/MDS is higher than previously reported with no evidence of a
      plateau (with approximately 40% of AL/MDS cases occurring after the 12th year of
      follow-up). Although hydroxyurea currently remains the first choice in the
      treatment of high-risk PV and ET patients, the use of nonleukemogenic drugs, such
      as interferon alpha (IFN-alpha) or anagrelide, should be assessed more widely in
      randomized trials using accurate diagnostic criteria and taking into account the
      presence of the JAK2 mutation, given that they may have an impact on disease
      evolution.

PMID- 16810618
TI  - Essential thrombocythemia/polycythemia vera and pregnancy: the need for an
      observational study in Europe.
AB  - The management of pregnant patients with essential thrombocythemia (ET) and
      polycythemia vera (PV) may be problematic. In the literature there are
      approximately 300 cases of pregnancies reported in ET and less than 50
      pregnancies reported in PV. To reduce the effect of reporting bias, we selected
      articles with either > 10 pregnancies or at least six patients, and here report
      on the outcome of 195 pregnancies in ET and 36 pregnancies in PV patients. The
      live birth rate was approximately 60% in ET and 58% in PV. Spontaneous abortion
      during the first trimester was the most frequent fetal complication, occurring in
      31% of ET pregnancies and in 22% of PV pregnancies, respectively. Major maternal
      complications were more frequent in PV compared with ET (44.4 versus 7.7%).
      Treatment with low-dose aspirin during pregnancy in ET seemed to reduce
      complications and also seemed beneficial during pregnancy in PV. In high-risk
      pregnancies, the additional use of low molecular weight heparin and/or interferon
      alpha should be considered. This article also describes a registry for an
      observational study concerning pregnancy in chronic Philadelphia chromosome
      negative myeloproliferative disorders within the European LeukemiaNet. A
      potential management algorithm for pregnancies in ET or PV is also provided.

PMID- 16810619
TI  - Update on diagnosis and management of essential thrombocythemia.
AB  - Patients with essential thrombocythemia carry a high risk for thromboembolic and
      bleeding events but they have an almost normal life expectancy. A careful
      evaluation of the medical history and an exact diagnosis is mandatory to estimate
      each patient's risk for morbidity and to choose the most appropriate treatment
      measure. In patients with the need of cytoreductive therapy, the benefits of
      therapy have to outweigh the potential risks of drug toxicities. Hydroxyurea is
      the most useful cytoreductive drug for elderly patients; in younger persons,
      interferon alpha or anagrelide may be the drugs of choice. The combination of
      anagrelide with acetylsalicylic acid may be contraindicated in patients with a
      history of bleeding.

PMID- 16810620
TI  - Treatment of polycythemia vera.
AB  - The selection of treatment for patients with polycythemia vera (PV) still is the
      subject of much discussion among hematologists. It is emphasized that important
      physiologic and pathogenic components of the illness relate not only to the
      erythroid cell, but also to the megakaryocyte. Both play essential roles in
      causing complications of the disease. Hematologists agree that the mainstay in
      treatment remains phlebotomy, a basic pillar of the concept of PRIMUM NON NOCERE.
      In general, the target levels for the hematocrit have been accepted as <or= 45%
      for men and <or= 42% for women. Low-dose aspirin, 80 to 100 mg daily, should be
      used as a basic component of therapy. The selection of the type of treatment for
      those patients who require some form of myelosuppression owing to the frequency
      of phlebotomy and/or its complications provides the basis for major discussion,
      confrontation, and disagreement. For the most part, alkylating agents are avoided
      owing to the established risk of secondary leukemia, but these drugs and
      radioactive phosphorous ( (32)P) still play a role in treating the very elderly
      patient or for those who have significant comorbid conditions. Whereas
      hydroxyurea remains the most frequently prescribed drug, limitations to its use
      as a therapeutic agent of choice include questions regarding its effectiveness,
      toxicity, and potential leukemogenicity. Interferon offers a rational choice of
      treatment owing to its broad physiologic effects on hematopoiesis. Whereas its
      effect in treating patients with PV is unequivocal, it is associated with side
      effects even when used properly. Moreover, it has only modest effect on Janus
      kinase 2 (JAK2) expression. Clearly, the best treatment for patients with PV is
      still sought. Perhaps more explicit exploitation of the JAK2 abnormality found in
      PV (and other myeloproliferative diseases) may provide more effective agents in
      the future.

PMID- 16810624
TI  - [Kunze H, Priebe S. Integrated care - perspective for psychiatry and
      psychotherapy. Psychiatry Prax 2006; 33: 53 -55].

PMID- 16810625
TI  - [Guideline-conformity of outpatient COPD management by pneumologists].
AB  - BACKGROUND: Several evidenced-based clinical guidelines are available for COPD
      which is the most frequent chronic respiratory disease. The purpose of this study
      was to evaluate the outpatient COPD management of pneumologists based on current
      national and international guidelines for the first time and to identify any
      deviations. METHODS: A nationwide prospective cross-sectional survey was
      performed as a multiple-choice questionnaire sent to 863 pneumologists in
      Germany. The product-neutral questions focused on the knowledge about, acceptance
      of and practical experience with current national and international COPD
      guidelines. RESULTS: 359 pneumologists (41.6 %) participated in the survey. 60.4
      % of the participants preferred the GOLD guideline over the German COPD guideline
      (33.4 %). 54.3 % considered bodyplethysmography as the diagnostic standard,
      followed by spirometry (38.4 %). However, only about 80 % were able to cite the
      correct spirometric criteria for classifying COPD severity. It is remarkable that
      many physicians still oriented to the outdated GOLD classification of 2001. The
      two most important treatment goals cited were to improve quality of life (82.2 %)
      and prevent exacerbations (63 %). Except for the criteria for the use of steroids
      and the implementation of pulmonary rehabilitation measures, treatment of COPD
      based on severity class was largely in compliance with the guidelines. However, a
      significant percentage of the pneumologists incorrectly assessed the evidence
      based clinical benefits of various therapeutic measures. CONCLUSION: The results
      of this survey show that most pneumologists adhere to guideline recommendations
      in daily practice and prefer the GOLD over the national COPD guideline. However,
      deficiencies in guideline conformity still exist with regard to severity
      classification and treatment of COPD.

PMID- 16810626
TI  - [Tuberculosis in the old medical history of Greeks].

PMID- 16810627
TI  - [Ethics of mechanical ventilation in end of life].
AB  - Invasiveness of interventions, complexity of diseases and patients' age are
      increasing in intensive care medicine. Ethical and legal issues are particularly
      challenging at the end of life of critically ill patients. At the borderline
      between intensive care and palliative medicine a significant amount of patients
      suffer from respiratory failure. Modern modes of mechanical ventilation may be
      able to improve ventilation and quality of life. On the other hand they may
      oppose a dignified death at the end of a long lasting chronic disease and e. g.
      prolong the suffering. In contrast to endotracheal intubation and invasive
      mechanical ventilation NIV enables patients to participate in the decision making
      process. While under normal circumstances, ethical standards dictate that
      patients themselves participate in the medical decision making process. For
      several reasons this is not always possible in intensive care medicine. However,
      chronically ill patients should get information from experts already at an early
      stage of the disease, go through a shared decision process and declare their will
      concerning interventions of intensive care medicine, e. g. mechanical
      ventilation. With respect to ethical and legal aspects of end of life this paper
      deals with chances of mechanical ventilation, including its withdrawal and
      withholding.

PMID- 16810628
TI  - [New antibiotics for the therapy of respiratory tract infections].
AB  - The need for new antibiotics is ongoing in view of manifold resistance
      developments. The resistance of Streptococcus pneumoniae against macrolides and
      penicillins in the USA already amounts to more than 30 %. The approval of new
      antibiotics, particularly those with a new mode of action, has been decreasing
      over the past years which is anticipated to result in a lack of resourceful
      therapy options in the future. Some new substances with good in vitro activity
      against S. pneumoniae have turned out to raise safety issues as shown for a
      number of quinolones. Likewise daptomycin, a lipopeptide with a new mechanism of
      action, did not show satisfying results due to its inactivation by surfactant.
      Established quinolones are levofloxacin and moxifloxacin, the latter being
      available as i. v. formulation since 2002. For ketolides, telithromycin (oral)
      and for azalides azithromycin (since 2005 as i. v. formulation) are available for
      antimicrobial therapy. Linezolid is the only approved oxazolidinone. Tigecycline,
      a tetracycline derivate, will be approved in 2006 in Germany. The latest approval
      regarding carbapenems was ertapenem in 2003, while doripenem, a new antibiotic
      from this group, is still under clinical development.

PMID- 16810629
TI  - [Diagnosis and treatment of pulmonary hypertension].

PMID- 16810631
TI  - Adeno-associated virus (AAV) serotypes 2, 4 and 5 display similar transduction
      profiles and penetrate solid tumor tissue in models of human glioma.
AB  - BACKGROUND: Adeno-associated viral (AAV) vectors are potent delivery vehicles for
      gene transfer strategies directed at the central nervous system (CNS), muscle and
      liver. However, comparatively few studies have described AAV-mediated gene
      transfer to tumor tissues. We have previously demonstrated that while AAV2 and
      Adenoviral (Ad) 5 vectors have similar broad host ranges in tumor-derived cell
      lines, AAV2 was able to penetrate human glioblastoma biopsy spheroids and
      xenografts more efficiently than Ad 5 vectors. These results suggested that AAV
      vectors could be suitable for therapeutic gene delivery to solid tumor tissue. In
      the present work, the transduction efficacy of AAV serotypes 4 and 5 were
      compared to AAV2, both in vitro and in intracranial GBM xenografts derived from
      patient biopsies implanted into nude rats. METHODS: AAV vector serotypes 2, 4,
      and 5 containing either the green fluorescent protein (GFP) or the bacterial beta
      galactosidase (lacZ) reporter gene were added to five different human glioma cell
      lines, to multicellular spheroids generated from glioblastoma patient biopsies,
      and to spheroids xenografted intracranially in nude rats. Transduction efficiency
      was assessed by fluorescence imaging, histochemistry, immunohistochemistry and
      flow cytometry. RESULTS: While all three AAV serotypes were able to transduce the
      glioma cell lines when added individually or when they were administered in
      concert, AAV2 transduced the glioma cells most effectively compared to AAV4 or
      AAV5. Upon infecting glioblastoma spheroids in vitro, all three AAV serotypes
      efficiently transduced cells located at the surface as well as within deeper
      layers of the spheroids. In addition, similarly to what was observed for AAV2 16,
      both AAV4 and AAV5 were able to transduce human glioblastoma xenografts implanted
      intracranially. CONCLUSIONS: In addition to the widely used AAV2 serotype, AAV4
      and AAV5 serotypes may also be used to transduce biologically diverse glioma cell
      lines. They also penetrate and transduce solid human tumor tissue derived from
      patient biopsies. Therefore, the data presented here provide a proof of principle
      for developing AAV4 and AAV5 as treatment vehicles for human malignant gliomas.

PMID- 16810630
TI  - [Magnetic resonance analysis of the subscapularis muscle after open anterior
      shoulder stabilization].
AB  - PURPOSE: Analysis of the magnetic resonance imaging of the subscapularis
      musculotendinous unit (SSC) after primary and revision open shoulder
      stabilization and their correlation with the clinical function. MATERIALS AND
      METHODS: In a retrospective cohort study, 13 patients (mean age of group A: 36.5
      years) after primary and 12 (mean age of group B: 34.2 years) after revision open
      stabilization underwent postoperative MRI of the shoulder. The digital data was
      analyzed with respect to the vertical und transverse diameters (V[slashed
      circle], T[slashed circle]) in a defined image slice. A signal intensity analysis
      was performed (infraspinatus/subscapularis signal-to-noise ratio = ISP/SSC SNR).
      The clinical examination included the SSC tests and signs and the Constant and
      Rowe score. Twelve healthy volunteers (group C) served as the control. RESULTS:
      From group C to group B, the mean V[slashed circle] of the SSC decreased
      significantly (p < 0.05) as did the mean T[slashed circle] of the cranial part of
      the SSC muscle (= crSSC) (p < 0.05). The mean T[slashed circle] of the caudal
      part of the SSC muscle (= caSSC) did not differ significantly between all groups
      (p > 0.05). The ISP-SSC SNR was significantly lower (p < 0.05) in the crSSC of
      groups A und B than in group C. In the caSSC, the SNR increased in groups A and
      B. In 53.8 % of group A and 92.3 % of group B, clinical signs of SSC
      insufficiency were found. There was no significant difference between the
      Constant and the Rowe score in both groups (p > 0.05). Complete tendon ruptures
      were not observed in any case. CONCLUSIONS: MRI enables semi-quantitative
      analysis of the postoperative changes of the subscapularis muscle. The decrease
      of the ISP/SSC SNR points to a fatty degeneration in the crSSC. The results
      provide indications of the causes of the clinical dysfunction of the
      subscapularis musculotendinous unit after open shoulder stabilization.

PMID- 16810632
TI  - Correlations between MRS and DTI in cerebral small vessel disease.
AB  - Cerebral small vessel disease results in lacunar infarcts and cognitive
      impairment. Diffusion tensor imaging (DTI) demonstrates a reduction in fractional
      anisotropy and increase in mean diffusivity, which correlates more strongly with
      cognition than conventional MRI. The underlying pathological basis for these DTI
      changes is not known. In this study magnetic resonance spectroscopy was used to
      determine the biochemical basis of these DTI alterations. Twenty-five patients
      with lacunar stroke and radiological leukoaraiosis were recruited. Chemical shift
      imaging (CSI) and DTI were performed on a 1.5 T MRI scanner. A region of interest
      was positioned in the white matter of the centrum semiovale. Multivoxel CSI data
      were processed and the metabolite ratios estimated. DTI parameters corresponding
      to the exact region of tissue excited by CSI were obtained. Mean spectroscopy
      data and DTI values for each subject were correlated. Univariate analysis
      revealed a positive correlation between N-acetyl aspartate-creatine (NAA/Cr) and
      fractional anisotropy (r = 0.52, p = 0.008), and a negative correlation with mean
      diffusivity (r = -0.51, p = 0.009). Results remained little changed after
      controlling for mean percentage lesion and mean percentage white matter per voxel
      (with fractional anisotropy r = 0.54, p = 0.008, and with mean diffusivity r = 
      0.52, p = 0.01). These findings are consistent with axonal loss or dysfunction,
      or both, accounting for at least part of the DTI abnormalities found in patients
      with small vessel disease. It provides evidence that DTI identifies axonal
      disruption in white matter tracts.

PMID- 16810633
TI  - A role for the transcription factor RelB in IFN-alpha production and in IFN-alpha
      stimulated cross-priming.
AB  - Chimeric mice generated with bone marrow from RelB-deficient (-/-), RelB
      heterozygous (+/-) and wild-type (+/+) mice were used to determine how total or
      partial absence of the transcription factor RelB in haematopoietic cells affects
      the immune response generated after lymphocytic choriomeningitis virus (LCMV)
      infection. In RelB(-/-) chimeras, early virus replication was enhanced and LCMV
      clearance was impaired. Although plasmacytoid dendritic cell numbers were
      similar, serum interferon (IFN)-alpha levels in RelB(-/-) and RelB(+/-) chimeras
      were markedly lower than in RelB(+/+) chimeras during early LCMV infection.
      Further, both RelB(-/-) and RelB(+/-) chimeras mounted a lower-magnitude LCMV
      specific CD8(+) T cell response than their RelB(+/+) counterparts, although the
      LCMV-specific CD8(+) T cells present were differentiated into functional
      cytotoxic cells. In LCMV-infected RelB(-/-) mice, induction of cross-priming to
      an independently injected soluble protein, which depends on the IFN-alpha/beta
      made during the viral infection, was also impaired. Notably, provision of
      exogenous IFN-alpha did not restore the ability of RelB(-/-) mice to cross-prime.
      In summary, these results show that the RelB/NF-kappaB pathway is required for
      optimal IFN-alpha production after LCMV infection and suggest a crucial role for
      RelB in IFN-alpha-stimulated cross-priming of CD8(+) T cell responses.

PMID- 16810634
TI  - Toll-like receptor engagement stimulates anti-snRNP autoreactive B cells for
      activation.
AB  - Autoreactive B cells are the source of pathogenic autoantibodies (autoAb) in
      systemic lupus erythematosus (SLE). Previous studies have demonstrated that anti
      small nuclear ribonucleoprotein particles (snRNP) B cells from normal background
      mice tolerize T cells in the periphery and do not secrete autoAb. In this study,
      we examined whether these anti-snRNP B cells can be activated for autoAb
      production by the engagement of Toll-like receptors (TLR). Anti-snRNP B cells
      proliferated vigorously and secreted abundant anti-snRNP autoAb upon exposure to
      CpG or polyriboinosinic polyribocytidylic acid [poly (I:C)] in vitro. In
      addition, the costimulatory molecules CD80 and CD86 were up-regulated. While both
      anti-snRNP B cells and wild-type B cells produced similar levels of IL-6 and IL
      10, anti-snRNP B cells secreted predominately IFN-gamma in response to CpG or
      poly (I:C) stimulation. Furthermore, we showed that in vivo engagement of TLR
      stimulated immature anti-snRNP B cells to further differentiate and produce
      autoAb and form germinal centers. The activated anti-snRNP B cells became
      expanded and migrated into the T-B cell interface. Moreover, TLR engagement
      directly or indirectly activated autoreactive B cells via a CD4 T cell
      independent manner. These results provide in vitro and in vivo evidence that
      BCR/TLR co-engagement promotes the activation of anti-snRNP B cells for autoAb
      production.

PMID- 16810636
TI  - Simultaneous quantification of chlorogenic acid and caffeic acid in rat plasma
      after an intravenous administration of mailuoning injection using liquid
      chromatography/mass spectrometry.
AB  - A simple, rapid and sensitive method was developed for the simultaneous
      quantification of chlorogenic acid (CGA) and caffeic acid (CA) in rat plasma
      using a high-performance liquid chromatography system coupled to a negative ion
      electrospray mass spectrometric analysis. The plasma sample preparation was a
      simple deproteinization by the addition of two volumes of acetonitrile followed
      by centrifugation. The analytes and internal standard ferulic acid were separated
      on an Intersil C8-3 column (5 mm; 250 x 2.1 mm) with acetonitrile/0.05%
      triethylamine solution (70:30, v/v) as mobile phase at a flow rate of 0.2 mL/min
      with an operating temperature of 30 degrees C. Detection was performed on a
      quadrupole mass spectrometer equipped with an electrospray ionization (ESI)
      source operated in selected ion monitoring (SIM) mode. Negative ion ESI was used
      to form deprotonated molecules at m/z 353 for chlorogenic acid, m/z 179 for
      caffeic acid, and m/z 193 for the internal standard ferulic acid. Linear
      detection responses were obtained for CGA concentrations ranging from 0.005 to
      2.0 microg/mL and for CA concentrations ranging from 0.010 to 2.0 microg/mL and
      the lower limits of quantitation (LLOQs) for CGA and CA were 0.005 and 0.01
      microg/mL, respectively. The intra- and inter-day precisions (RSD%) were within
      9.0% for both analytes. Deviation of the assay accuracies was within +/-10.0% for
      both analytes. Their average recoveries were greater than 88.0%. Both analytes
      were proved to be stable during all sample storage, preparation and analytic
      procedures. The method was successfully applied to the pharmacokinetic study of
      CGA and CA following an intravenous dose of 5 mL/kg mailuoning injection to rats.

PMID- 16810635
TI  - Early type I interferon-mediated signals on B cells specifically enhance
      antiviral humoral responses.
AB  - Type I interferons (IFN-I) limit viral spread by inducing antiviral genes in
      infected target cells and by shaping the adaptive response through induction of
      additional cytokines. Vesicular stomatitis virus (VSV) efficiently triggers the
      production of IFN-I in mice, and it is suggested that IFN-alpha is induced after
      binding of VSV to TLR7 in infected cells. Our study with virus-specific B cell
      receptor-transgenic mice demonstrates here that IFN-I directly fuel early humoral
      immune responses in vivo. VSV-specific B cells that lacked IFN-alpha/beta
      receptors were considerably impaired in plasma cell formation and in generating
      antiviral IgM. At low viral titers, production of IFN-alpha following VSV
      infection was independent of TLR7-mediated signals. Interestingly, however, TLR7
      ligation in B cells increased the formation of early antiviral IgM. These
      findings indicate that IFN-alpha-mediated augmentation of specific B cell
      responses is a partially TLR7- and virus dose-dependent mechanism.

PMID- 16810637
TI  - Quantification of tizanidine in human plasma by liquid chromatography coupled to
      tandem mass spectrometry.
AB  - A simple, sensitive and rapid high-performance liquid chromatography/positive ion
      electrospray tandem mass spectrometry (MS/MS) method was developed and validated
      for the assay of tizanidine in human plasma. Following liquid-liquid extraction,
      the analytes were separated using an isocratic mobile phase on a reversed-phase
      column and analyzed by MS/MS in the selected reaction monitoring mode. The assay
      exhibited a linear dynamic range of 50-5000 pg/mL for tizanidine in human plasma.
      The lower limit of quantification was 50 pg/mL with a relative standard deviation
      of less than 13%. Acceptable precision and accuracy were obtained for
      concentrations over the standard curve range. A run time of 2.5 min for each
      sample made it possible to analyze more than 300 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- 16810638
TI  - Product ion mass spectra of amphetamine-type substances, designer analogues, and
      ketamine using ultra-performance liquid chromatography/tandem mass spectrometry.
AB  - This paper describes the application of ultra-performance liquid
      chromatography/tandem mass spectrometry (UPLC/MS/MS) technology to separate and
      identify amphetamine-type substances (amphetamine, methamphetamine), common and
      novel designer analogues (MDA, MDMA, PMA, 4-MTA, MBDB), and ketamine using
      Acquity UPLC/Micromass Quattro Micro API mass spectrometer instrumentation
      (Waters Corporation, USA). From injection of drug reference standards, it was
      demonstrated that these compounds can be identified by product ion mass spectra
      in less than 4 min total analysis time, indicating that the technological
      advancements associated with UPLC/MS/MS allow it to serve as a powerful
      analytical tool for high-throughput testing. In addition to demonstrating the
      separation and response of these drug compounds under the stated UPLC/MS/MS
      conditions, we believe the acquired product ion spectra will be a beneficial
      reference to laboratories interested in incorporating the use of this technology
      in the routine analysis of drugs of abuse.

PMID- 16810639
TI  - C-terminal amino acid residue loss for deprotonated peptide ions containing
      glutamic acid, aspartic acid, or serine residues at the C-terminus.
AB  - Deprotonated peptides containing C-terminal glutamic acid, aspartic acid, or
      serine residues were studied by sustained off-resonance irradiation collision
      induced dissociation (SORI-CID) in a Fourier transform ion cyclotron resonance
      (FT-ICR) mass spectrometer with ion production by electrospray ionization (ESI).
      Additional studies were performed by post source decay (PSD) in a matrix-assisted
      laser desorption ionization/time-of-flight (MALDI/TOF) mass spectrometer. This
      work included both model peptides synthesized in our laboratory and bioactive
      peptides with more complex sequences. During SORI-CID and PSD, [M - H]- and [M -
      2H]2- underwent an unusual cleavage corresponding to the elimination of the C
      terminal residue. Two mechanisms are proposed to occur. They involve nucleophilic
      attack on the carbonyl carbon of the adjacent residue by either the carboxylate
      group of the C-terminus or the side chain carboxylate group of C-terminal
      glutamic acid and aspartic acid residues. To confirm the proposed mechanisms,
      AAAAAD was labelled by 18O specifically on the side chain of the aspartic acid
      residue. For peptides that contain multiple C-terminal glutamic acid residues,
      each of these residues can be sequentially eliminated from the deprotonated ions;
      a driving force may be the formation of a very stable pyroglutamatic acid
      neutral. For peptides with multiple aspartic acid residues at the C-terminus,
      aspartic acid residue loss is not sequential. For peptides with multiple serine
      residues at the C-terminus, C-terminal residue loss is sequential; however,
      abundant loss of other neutral molecules also occurs. In addition, the presence
      of basic residues (arginine or lysine) in the sequence has no effect on C
      terminal residue elimination in the negative ion mode.

PMID- 16810640
TI  - A mass spectrometric investigation on the possible role of tryptophan and 7
      hydroxytryptophan in melanogenesis.
AB  - The activity of tyrosinase and peroxidase + H2O2 in promoting melanogenesis from
      tryptophan (Trp) and 7-hydroxytryptophan (7-HTP) has been investigated. The
      reaction samples have been drawn at different reaction times and analysed by
      MALDI mass spectrometry. The data obtained showed that tryptophan undergoes,
      under tyrosinase and peroxidase action, an oligomerization process mainly due to
      the reaction of anthranilic acid (AA) and Trp. However, analysing the UV and
      fluorescence data, it is seen that the oligomers cannot belong to the melanin
      pattern, but their possible role in melanogenesis is not to be excluded. Once it
      reacts with the two enzymes, 7-hydroxytryptophan leads to dark brown products,
      indicating its possible role in melanin production. In contrast to what was
      observed in the case of 5-hydroxytryptophan, for which oligomers were constituted
      by 5-hydroxytryptophan (5-HTP) and 5-hydroxytryptamine (5-HT) units, the MALDI
      data indicate a sharply different behaviour for 7-HTP. In fact, in the case of 5
      hydroxytryptophan, oligomerization takes place through the formation of 5
      hydroxytryptamine and the oligomerization products are due to mixed 5-HTP-5-HT
      oligomers. In the case of 7-hydroxytryptophan, the formation of 7
      hydroxytryptamine (7-HT) is also observed, but it does not seem to play any role;
      the only oligomerization products formed are due to the reaction of 7
      hydroxytryptophan and AA. The data so obtained indicate that 7-hydroxytryptophan
      acts like an effective melanin precursor in the presence of both tyrosinase and
      peroxidase + H2O2.

PMID- 16810642
TI  - Alfred Nier and the sector field mass spectrometer.
AB  - Science and technology are intimately related, and advances in science often
      become possible with the availability of new instrumentation. This has certainly
      been the case in mass spectrometry, which is used in so many scientific
      disciplines. Originally developed as an instrument for research in physics it was
      used in the discovery of isotopes, their recognition as the fundamental species
      comprising the elements, and the investigation of elemental isotopic composition.
      Isotope ratio mass spectrometry is a metrological technique of the highest order,
      and has been widely used in chemical, biochemical, cosmochemical, environmental,
      geological, physical, and nuclear research. Mass spectrometry presently plays a
      key role not only in scientific research, but also in industrial operations. This
      paper highlights the role that Alfred Otto Carl Nier played in bringing mass
      spectrometry into the mainstream of science. Nier's career spanned a remarkable
      period in science, and he made crucial contributions to atomic weights,
      geochronology, isotope geochemistry, nuclear physics, and space science. He is
      widely viewed as the 'father of modern mass spectrometry', because of his genius
      with instrumentation, his innovations, and the generosity with which he shared
      his ideas and designs. It is timely to remember his fundamental work in mass
      spectrometry, particularly the development of the sector field mass spectrometer,
      which is still the instrument of choice for many isotope scientists some 66 years
      after its first appearance in 1940.

PMID- 16810641
TI  - Zirconia-coated graphite adsorption bar micro-extraction combined with ETV-ICP-MS
      for the determination of trace amounts of Cd, Hg and Pb in environmental and
      biological samples.
AB  - In this work, a new and simple micro-extraction method termed graphite adsorption
      bar micro-extraction was developed, for the first time, for electrothermal
      vaporization inductively coupled plasma mass spectrometry (ETV-ICP-MS)
      determination of trace Cd, Hg and Pb. In this method, the graphite bar was first
      coated with zirconia and then inserted into the sample solution for extraction.
      The graphite bar enriched with the analytes was inserted directly into a graphite
      tube, and subsequently analyzed by ETV-ICP-MS according to an established
      temperature program. The experimental parameters, which had influence on the
      extraction and vaporization, were systematically investigated and the optimal
      experimental conditions were established. Under the optimized conditions, the
      detection limits of the method were 0.05, 0.42 and 0.06 pg/ml for Cd, Hg and Pb
      and the relative standard deviations (RSDs) for 11 replicates at the 0.1 ng/ml
      level were 7.4, 8.2 and 7.7%, respectively. The proposed method was successfully
      applied to the determination of trace Cd, Hg and Pb in environmental and
      biological samples. The results of the experiments indicate that the method has a
      high enrichment factor and sample utilization efficiency. Furthermore, the method
      is fast and environment-friendly.

PMID- 16810644
TI  - On the determination of molecular weight distributions of asphaltenes and their
      aggregates in laser desorption ionization experiments.
AB  - Molecular weight distributions (MWD) of asphaltenes and their aggregates have
      been investigated in laser desorption ionization (LDI) mass spectrometric
      experiments. A systematic investigation of the dependence of the measured MWD on
      the asphaltene sample density and on the laser pulse energy allows the assignment
      of most probable molecular weights within 300-500 amu and average molecular
      weights of 800-1000 amu for the monomeric asphaltenes, as well as for the
      estimation of the contribution from asphaltene clusters in typical LDI
      measurements. The results serve to reconcile the existing controversy between
      earlier mass spectrometric characterizations of asphaltenes based on laser
      desorption techniques by different groups. Furthermore, the MWD measurements
      performed on particularly dense samples yield an additional differentiated broad
      band peaking around 9000-10,000 amu and extending over 20,000 amu, not observed
      previously in LDI experiments, thereby revealing a strong propensity of the
      asphaltenes to form clusters with specific aggregation numbers, which is in
      qualitative agreement with previous theoretical predictions and with the
      interpretation of measurements performed with other techniques.

PMID- 16810645
TI  - A new strategy utilizing electrospray ionization-quadrupole ion trap mass
      spectrometry for the qualitative determination of GnRH peptides.
AB  - Numerous forms of the neurotransmitter GnRH have been discovered in vertebrates
      and invertebrates. Methods used for identification of these peptides are
      laborious and often require the application of multiple, confirmatory techniques.
      In this study, we investigate whether HPLC-MS/MS and de novo sequencing
      techniques applied to whole peptide analysis can provide a simpler approach to
      GnRH characterization. Experiments were performed with six GnRH forms (chicken I,
      chicken II, lamprey III, mammalian, salmon and seabream) to determine whether
      MS/MS spectra would be dominated by proline-directed fragmentation to the
      detriment of obtaining sufficient fragmentation for sequencing. While the
      expected b8 fragment was prominent, sufficient ion series were obtained for the
      six GnRH peptides to provide sequence identification. On the basis of the
      patterns observed for six model peptides, similar fragmentation patterns are
      expected for other GnRH forms. To confirm the applicability of the method,
      extracts from Sprague-Dawley rat brains were examined. These experiments confirm
      the presence of mammalian GnRH and a posttranslationally modified form of
      mammalian GnRH, hydroxyproline9 GnRH, in Sprague-Dawley rat brains and
      demonstrate that ESI-MS/MS techniques provide a valuable addition to existing
      qualitative methods.

PMID- 16810646
TI  - Identification of isomeric flavonoid glucuronides in urine and plasma by metal
      complexation and LC-ESI-MS/MS.
AB  - Noncovalent complexes were used for structural determination and isomer
      differentiation of flavonoid glucuronides. Several flavonoid glucuronides
      including naringenin-7-O-glucuronide, synthesized here for the first time, were
      used as test compounds. Electrospray ionization quadrupole ion trap mass
      spectrometry with collision-induced dissociation (CID) was used to analyze
      complexes of the form [Co(II) (L-H) (Aux)]+ and [Co(II) (L-H) (Aux)2]+, in which
      L is the flavonoid glucuronide and Aux is a phenanthroline-based ligand. These
      complexes yielded characteristic fragmentation patterns that facilitated
      assignment of the substitution position of the glucuronides. The methods were
      adapted to liquid chromatography/tandem mass spectrometry (LC-MS/MS) with
      postcolumn cobalt complexation and were tested on extracts from biological
      fluids. The metabolites naringenin-7-O-glucuronide and naringenin-4'-O
      glucuronide were detected in human urine following the consumption of grapefruit
      juice. Isomeric quercetin glucuronides were identified and differentiated after
      spiking rat plasma at the 1 microM level, proving that the new methods are
      effective at biologically relevant concentrations.

PMID- 16810647
TI  - Investigation of low-abundant in vitro metabolites of stable isotope-labelled
      BAL4815 by accurate mass capillary-LC-ESI-qTof-MS and MS/MS.
AB  - The metabolic profile of BAL4815, an antifungal azole drug, was determined using
      in vitro rat hepatocyte incubations and subsequent analysis by capillary LC-qTof
      MS and MS/MS including accurate mass determination. For the detection of the
      metabolites, a mixture of the drug and its deuterium-labelled analogue was used
      for incubations. Metabolic stability of BAL4815 was high in cultured rat
      hepatocytes. However, several low-abundant metabolites were detected by the use
      of capillary LC-qTof-MS and manual investigation of the data. The peak intensity
      of the most abundant metabolite was close to the limit of detection. Except for
      an apparent oxidation product, the masses of the other detected metabolites could
      not be assigned to a single and frequently occurring biotransformation. Accurate
      mass determination and possible elemental compositions suggested that metabolism
      occurred through a combination of glutathionylation and defluorination. This was
      verified using accurate mass MS/MS. The use of accurate mass measurements and the
      derived suggestions for the elemental compositions were essential to elucidate
      this atypical metabolic pathway. A mass accuracy better than 8 ppm could be
      achieved for most assigned MS and MS/MS signals with intensities less than 6 cps
      in the spectra.

PMID- 16810648
TI  - New designer drug 4-iodo-2,5-dimethoxy-beta-phenethylamine (2C-I): studies on its
      metabolism and toxicological detection in rat urine using gas
      chromatographic/mass spectrometric and capillary electrophoretic/mass
      spectrometric techniques.
AB  - Studies are described on the metabolism and the toxicological analysis of the
      phenethylamine-derived designer drug 4-iodo-2,5-dimethoxy-beta-phenethylamine (2C
      I) in rat urine using gas chromatographic/mass spectrometric (GC/MS) techniques,
      and for a particular question, using capillary electrophoretic/mass spectrometric
      (CE/MS) techniques. The identified metabolites indicated that 2C-I was
      metabolized on the one hand by O-demethylation in position 2 and 5, respectively,
      followed either by N-acetylation or by deamination with subsequent oxidation to
      the corresponding acid or reduction to the corresponding alcohol, respectively.
      The latter metabolite was hydroxylated in beta-position and further oxidized to
      the corresponding oxo metabolite. On the other hand, 2C-I was metabolized by
      deamination with subsequent oxidation to the corresponding acid or reduction to
      the corresponding alcohol, respectively. 2C-I and most of its metabolites were
      partially excreted in conjugated form. The authors' systematic toxicological
      analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid
      liquid extraction and microwave-assisted acetylation allowed the detection of an
      intake of a dose of 2C-I in rat urine that corresponds to a common drug users'
      dose. Assuming similar metabolism, the described STA procedure should be suitable
      for proof of an intake of 2C-I in human urine.

PMID- 16810649
TI  - A rapid and sensitive liquid chromatography/positive ion tandem mass spectrometry
      method for the determination of cimetropium in human plasma by liquid-liquid
      extraction.
AB  - We have developed and validated a simple detection system with high-performance
      liquid chromatography (HPLC) with positive ion electrospray ionization tandem
      mass spectrometry (ESI-MS/MS) for determining cimetropium levels in human plasma
      using scopolamine butyl bromide as an internal standard (I.S.). The acquisition
      was performed in the multiple reaction monitoring (MRM) mode, by monitoring the
      transitions: m/z 357.9 > 103.1 for cimetropium and m/z 359.9 > 103.1 for butyl
      scopolamine. The method involves a simple single-step liquid-liquid extraction
      with dichloromethane. The analyte was chromatographed on an YMC C18 reversed
      phase chromatographic column by isocratic elution with 10 mM ammonium formate
      buffer-methanol (19:81, v/v; adjusted to pH 4.0 with formic acid). The results
      were linear over the studied range (0.2-100 ng ml(-1)), with r2 = 1.0000, and the
      total analysis time for each run was 2 min. Intra- and interassay precisions were
      0.70-8.54% and 1.08-4.85%, respectively, and intra- and interassay accuracies
      were 97.56-108.23% and 97.48-103.91%, respectively. The lower limit of
      quantification (LLOQ) was 0.2 ng ml(-1). At this concentration, mean intra- and
      interassay precisions were 8.54% and 4.85%, respectively, and mean intra- and
      interassay accuracies were 97.56% and 98.91%, respectively. The mean recovery
      ranged from 62.71 +/- 4.06 to 64.23 +/- 2.32%. Cimetropium was found to be stable
      in plasma samples under typical storage and processing conditions. The devised
      assay was successfully applied to a pharmacokinetic study of cimetropium bromide
      administered as a single oral dose (150 mg) to healthy volunteers.

PMID- 16810651
TI  - A spiropyran-based ensemble for visual recognition and quantification of cysteine
      and homocysteine at physiological levels.

PMID- 16810650
TI  - Valence tautomerism in octahedral and square-planar phenoxyl-nickel(II)
      complexes: are imino nitrogen atoms good friends?
AB  - The two tetradentate ligands H(2)L and H(2)L(Me) afford the slightly distorted
      square-planar low-spin Ni(II) complexes 1 and 2, which comprise two coordinated
      phenolate groups. Complex 1 has been electrochemically oxidized into 1(+), which
      contains a coordinated phenoxyl radical, with a contribution from the nickel
      orbital. In the presence of pyridine, 1(+) is converted into 1(Py) (+), an
      octahedral phenolate nickel(III) complex with two pyridines axially coordinated:
      An intramolecular electron transfer (valence tautomerism) is promoted by the
      geometrical changes, from square planar to octahedral, around the metal center.
      The tetradentate ligand H(2)L(Me), in the presence of pyridine, and the
      hexadentate ligand H(2)L(Py) in CH(2)Cl(2) afford, respectively, the octahedral
      high-spin Ni(II) complexes 2(Py) and 3, which involve two equatorial phenolates
      and two axially coordinated pyridines. At 100 K, the one-electron-oxidized
      product 2(Py) (+) comprises a phenoxyl radical ferromagnetically coupled to the
      high-spin Ni(II) ion, with large zero-field splitting parameters, while 3(+)
      involves a phenoxyl radical antiferromagnetically coupled to the high-spin Ni(II)
      ion.

PMID- 16810652
TI  - A surface-bound DNA switch driven by a chemical oscillator.

PMID- 16810653
TI  - Silver-catalyzed hydroamination of siloxy alkynes.

PMID- 16810654
TI  - Structure-based synthetic mimicry of discontinuous protein binding sites:
      inhibitors of the interaction of Mena EVH1 domain with proline-rich ligands.
AB  - The Mena EVH1 domain, a protein-interaction module involved in actin-based cell
      motility, recognizes proline-rich ligand motifs, which are also present in the
      sequence of the surface protein ActA of Listeria monocytogenes. The interaction
      of ActA with host Mena EVH1 enables the bacterium to actively recruit host actin
      in order to spread into neighboring cells. Based on the crystal structure of Mena
      EVH1 in complex with a polyproline peptide ligand, we have generated a range of
      assembled peptides presenting the Mena EVH1 fragments that make up its
      discontinuous binding site for proline-rich ligands. Some of these peptides were
      found to inhibit the interaction of Mena EVH1 with the ligand pGolemi. One of
      them was further characterized at the level of individual amino acid residues;
      this yielded information on the contribution of individual positions of the
      peptides to the interaction with the ligand and identified sites for future
      structure optimization.

PMID- 16810655
TI  - Assessing the structural stability of designed beta-hairpin peptides in the
      cytoplasm of live cells.

PMID- 16810656
TI  - A phenol quaternary ammonium porphyrin as a potent telomerase inhibitor by
      selective interaction with quadruplex DNA.

PMID- 16810658
TI  - Peptide-capped gold nanoparticles: towards artificial proteins.
AB  - Peptides can be designed to form self-assembled monolayers on gold nanoparticles
      to give nanomaterials with some chemical properties analogous to those of
      proteins. A variety of molecular-recognition properties are readily integrated
      within the peptide monolayer. Monofunctionalized nanoparticles are obtained by
      using separation methods that have been optimized for proteins. Recent
      applications as artificial enzymes and artificial enzyme substrates are
      presented. The limitations and long-term potential of peptide-capped
      nanoparticles as artificial proteins are discussed.

PMID- 16810657
TI  - Unusually strong positive cooperativity in binding of peptides to latent membrane
      protein-1 DNA fragments of the Epstein-Barr viral gene.
AB  - The DNA-binding preferences of two oligopeptide amides, (His-Pro-Arg-Lys)(3)NH(2)
      (HR-12) and (Ser-Pro-Arg-Lys)(3)NH(2) (SP-12), have been examined by quantitative
      DNase I footprinting studies. Two different DNA fragments were investigated: a
      pair of 5'-(32)P-labeled duplexes from pBR322 with one or other of the
      complementary strands labeled and a corresponding pair of 5'-(32)P-labeled
      duplexes representing fragments of the latent membrane protein (LMP-1) gene from
      a pathogenic Epstein-Barr virus variant derived from nasopharyngeal carcinoma.
      The major objective was to examine molecular recognition and cooperative features
      associated with sequence-selective binding of synthetic peptides to the LMP-1
      fragments. At various binding sites on the pBR322 fragments, Hill coefficients
      (n(H)) ranging from 1.9-2.2 were observed; these results indicate modest positive
      cooperativity between binding sites for both peptides. By contrast, unusually
      high values of n(H), ranging from 4.0-9.3, were observed at various binding sites
      on the LMP-1 fragments. Allosteric models can be constructed to interpret the
      observed cooperative interactions between different DNA recognition sites in the
      LMP-1 gene upon binding of the peptide ligands. It is noteworthy that these
      models feature a novel network of cooperativity interconnecting multiple DNA
      allosteric sites. The evidence of sequence selectivity and strong cooperativity
      discovered in this work may prove to be a general feature of peptide interactions
      with some nucleic acids.

PMID- 16810659
TI  - Electrochemically driven three-phase interlines into insulator compounds:
      electroreduction of solid SiO2 in molten CaCl2.
AB  - The electrochemical reduction of solid SiO2 (quartz) to Si is studied in molten
      CaCl2 at 1173 K. Experimental observations are compared and agree well with a
      novel penetration model in relation with electrochemistry at the dynamic
      conductor|insulator|electrolyte three-phase interlines. The findings show that
      the reduction of a cylindrical quartz pellet at certain potentials is mainly
      determined by the diffusion of the O(2-) ions and also the ohmic polarisation in
      the reduction-generated porous silicon layer. The reduction rate increases with
      the overpotential to a maximum after which the process is retarded, most likely
      due to precipitation of CaO in the reaction region (cathodic passivation). Data
      are reported on the reduction rate, current efficiency and energy consumption
      during the electroreduction of quartz under potentiostatic conditions. These
      theoretical and experimental findings form the basis for an in-depth discussion
      on the optimisation of the electroreduction method for the production of silicon.

PMID- 16810660
TI  - Velocity map imaging study of the photodissociation of CH3SH: internal energy
      distribution of the SH fragment.

PMID- 16810661
TI  - Gas-phase reactions of atomic lanthanide cations with D2O: room-temperature
      kinetics and periodicity in reactivity.
AB  - Reactions of atomic lanthanide cations (excluding Pm+) with D2O have been
      surveyed in the gas phase using an inductively coupled plasma/selected-ion flow
      tube (ICP/SIFT) tandem mass spectrometer to measure rate coefficients and product
      distributions in He at 0.35+/-0.01 Torr and 295+/-2 K. Primary reaction channels
      were observed corresponding to O-atom transfer, OD transfer and D2O addition. O
      atom transfer is the predominant reaction channel and occurs exclusively with
      Ce+, Nd+, Sm+, Gd+, Tb+ and Lu+. OD transfer is observed exclusively with Yb+,
      and competes with O-atom transfer in the reactions with La+ and Pr+. Slow D2O
      addition is observed with early lanthanide cation Eu+ and the late lanthanide
      cations Dy+, Ho+, Er+ and Tm+. Higher-order sequential D2O addition of up to five
      D2O molecules is observed with LnO+ and LnOD+. A delay of more than 50 kcal mol(
      1) is observed in the onset of efficient exothermic O-atom transfer, which
      suggests the presence of kinetic barriers of perhaps this magnitude in the
      exothermic O-atom transfer reactions of Dy+, Ho+, Er) and Tm+ with D2O. The
      reaction efficiency for O-atom transfer is seen to decrease as the energy
      required to promote an electron to make two non-f electrons available for bonding
      increases. The periodic trend in reaction efficiency along the lanthanide series
      matches the periodic trend in the electron-promotion energy required to achieve a
      d1s1 or d2 excited electronic configuration in the lanthanide cation, and also
      the periodic trends across the lanthanide row reported previously for several
      alcohols and phenol. An Arrhenius-like correlation is also observed for the
      dependence of D2O reactivity on promotion energy for early lanthanide cations,
      and exhibits a characteristic temperature of 2600 K.

PMID- 16810662
TI  - The effect of positive writing on emotional intelligence and life satisfaction.
AB  - This study explored the effect of writing about positive emotional experiences on
      emotional intelligence and life satisfaction. One hundred and seventy-five adults
      wrote about one of the following three topics: positive experiences with a cue
      for emotion regulation reflection, positive experiences without this cue, or a
      control writing topic. Multivariate analysis showed a significant time (pretest,
      posttest, and follow-up) by group effect. Writing about positive emotional
      experiences with an emotion regulation cue led to significant increases in
      emotional intelligence and life satisfaction at posttest and the increase in life
      satisfaction was maintained at 2-week follow-up. Further, participants who were
      cued to reflect on emotional regulation while writing about positive experiences
      rated their emotional intelligence significantly higher than the participants in
      the control writing group both at posttest and at follow-up. There were no
      significant differences in emotional intelligence or life satisfaction between
      those who were cued to reflect on emotional regulation while writing about
      positive experiences and those who wrote about positive experiences without such
      a cue.

PMID- 16810663
TI  - Therapeutic alliance mediates the relationship between interpersonal problems and
      depression outcome in a cohort of multiple sclerosis patients.
AB  - The relationship among therapeutic alliance, psychotherapy outcomes, and
      interpersonal problems was examined. The present study hypothesized therapeutic
      alliance would mediate the relationship between interpersonal functioning and
      outcome among patients with multiple sclerosis entering psychotherapy for
      depression. Nineteen clients received 16 weeks of individual cognitive-behavioral
      therapy (CBT) for depression as described by D. C. Mohr, A. C. Boudewyn, D. E.
      Goodkin, A. Bostrom, and L. Epstein (2001). Participants completed the Beck
      Depression Inventory (BDI; Beck, Ward, Mendelson, Mock, & Erbaugh, 1961), the
      Inventory of Interpersonal Problems-Circumplex (IIP-C; Alden, Wiggins, & Pincus,
      1990), and the Working Alliance Inventory-Client Form (WAI-C; Horvath &
      Greenberg, 1989). The IIP-C significantly predicted Week 16 BDI and the WAI-C at
      4 weeks. When controlling for the WAI-C, the relationship between the IIP-C and
      BDI was no longer significant, supporting the mediational hypothesis.

PMID- 16810664
TI  - The synergy of ChemMatrix resin and pseudoproline building blocks renders RANTES,
      a complex aggregated chemokine.
AB  - Traditionally, solid-phase synthesis has relied on polystyrene-based resins for
      the synthesis of all kinds of peptides. However, due to their high
      hydrophobicity, these resins have certain limitations, particularly in the
      synthesis of complex peptides, and in such cases, poly(ethylene glycol) (PEG)
      based resins are often found to give superior results. Another powerful strategy
      for expediting the assembly of complex peptides is to employ pseudoproline
      dipeptides. These derivatives disrupt the interactions among chains that are
      usually the cause of poor coupling yields in aggregated sequences. Here we report
      on an efficient stepwise solid-phase synthesis of RANTES (1-68) by combining the
      advantages of the totally PEG-based ChemMatrix resin and pseudoproline
      dipeptides.

PMID- 16810665
TI  - Clinical action: introduction to the special section on the action perspective in
      clinical psychology.
AB  - Action theory (AT) is an emerging theoretical and empirical paradigm that is
      based on multiple perspectives. The common denominator of these perspectives is
      their depiction of the individual as actively shaping his or her interpersonal
      environment. The purpose of this special section is to evaluate the impact of AT
      on clinical psychology. To that effect, articles that focus on a broad range of
      topics, including stress and depression, chronic pain, child and adolescent
      development, clinical case formulation, psychotherapy for suicidal patients, and
      public mental health policy in relation to recovery from psychosis have been
      assembled. Presenting novel conceptualizations and data on the ways in which
      individuals actively shape their environment, these articles highlight the
      potential of AT for improving clinical science and practice.

PMID- 16810666
TI  - Stress generation in depression: reflections on origins, research, and future
      directions.
AB  - Depressed individuals report higher rates of stressful life events, especially
      those that have occurred in part because of the person's characteristics and
      behaviors affecting interpersonal interactions. Termed stress generation, this
      phenomenon draws attention to the role of the individual as an active contributor
      rather than passive player in his or her environment, and is therefore an example
      of action theory. In this article, the author speculates about the intellectual
      origins of her stress generation perspective, and notes somewhat similar
      transactional approaches to the stress-disorder link outside of depression
      research. The literature on stress generation in depression is reviewed,
      including studies that attempt to explore its correlates and predictors, covering
      clinical, contextual, family, genetic, cognitive, interpersonal, and personality
      variables. Empirical and conceptual gaps in our understanding of processes
      contributing to stressors in the lives of depressed people remain. The author
      concludes with suggestions for further research, with the goal of furthering
      understanding both of mechanisms of depression and of dysfunctional interpersonal
      processes, as well as development of effective interventions to help break the
      stress-recurrence cycle of depression.

PMID- 16810667
TI  - Context in action: implications for the study of children and adolescents.
AB  - Action theories acknowledge the reciprocal nature of the relationship between
      individual action and social context. In this article, the author discusses
      various ways that the social context and the individual's actions can interact in
      childhood and adolescence. From an ecological perspective, emphasis is placed on
      two main issues: Children and adolescents develop within an interactive web of
      social contexts, and the examination of some contexts without taking into account
      others can lead to an incomplete and inaccurate accounting of the role of the
      social environment. Social contexts are frequently dynamic systems that fluctuate
      over time, and the extent to which children and adolescents can exert effortful
      control over changes in contexts varies. Implications of the ecological
      perspective for action-oriented research are discussed.

PMID- 16810669
TI  - The action formulation: a proposed heuristic for clinical case formulation.
AB  - The authors propose the action formulation (TAF), a heuristic for clinical case
      formulation. The action formulation relies on the action perspective, which
      depicts individuals as actively shaping their environment, and is premised upon
      four guidelines: (a) map the client's social environment, focusing on sources of
      support, chronic interpersonal difficulties, and negative and positive life
      events; (b) identify how the clients, in the context of their personalities,
      psychopathologies, and strengths, actively influence their environment; (c)
      differentiate between maladaptive, risk-related, interpersonal cycles, and
      adaptive, protective-based ones; and (d) tailor integrative techniques to short
      circuit the former cycles and bolster the latter ones. Links between TAF and
      emerging issues in clinical assessment are discussed.

PMID- 16810670
TI  - Leading a horse to water: an action perspective on mental health policy.
AB  - Following publication of several landmark policy documents beginning in 1999,
      there are unprecedented opportunities for reforming mental health care to meet
      the needs of persons with mental illness. In this article, the authors suggest
      that transforming mental health requires dramatic changes in theory as well as in
      policy and practice, offering action theory as a corrective for a clinical
      psychology that has yet to view people as active agents shaping their own lives.
      A participatory approach to policy development and adoption of an action-oriented
      model of clinical practice provide examples of the shift, which results from
      treating people to enhancing their access to opportunities and offering them the
      in vivo supports they need to pursue meaningful lives even while disabled.

PMID- 16810668
TI  - Daily interpersonal events in pain patients: applying action theory to chronic
      illness.
AB  - Action theory proposes that individuals actively shape and then respond to their
      environments, highlighting the role of stable person characteristics in the
      development and maintenance of life's interpersonal difficulties. In this study,
      the authors adopt the action perspective in their examination of predictors of
      daily interpersonal events among chronic pain patients with rheumatoid arthritis.
      They probe the extent to which stable symptoms of illness explained between
      person variation, and fluctuating symptoms explain day-to-day variation in both
      positive and negative events. Their evaluation of patients' daily diary reports
      indicate that between-person differences accounted for more variance in the
      occurrence of positive events relative to negative events (48% vs. 31%,
      respectively). Likewise, between-person factors accounted for more variance in
      appraisals of positive compared to negative events across relationship domains.
      Both intractable illness symptoms and disability, and daily fluctuations in pain
      and fatigue, were only weakly related to patients' reports of their interpersonal
      experiences. Consistent with action theory, these results suggest that stable
      person characteristics are strongly related to daily stressors and particularly
      daily positive events in pain patients, but still account for less than 50% of
      the variance in events and their appraisals. In contrast, elevations in illness
      related features, both between individuals and within individuals from day-to
      day, are not robust predictors of positive or negative social exchanges. These
      findings point to the value of capturing the experiences of individuals
      intensively over time, an approach that can help to elaborate the contributions
      of both stable factors and circumstance in shaping social contexts in chronic
      illness.

PMID- 16810671
TI  - Freshmen adaptation to university life: depressive symptoms, stress, and coping.
AB  - Attending a university for the first time can be a stressful experience for many
      new college students. This study examines the relationships among femininity and
      masculinity, depressive symptomatology, levels of stress, and the types of coping
      strategies used by college freshmen. Results of this study suggest that these
      variables were related uniquely for first-year college students. Masculinity and
      femininity significantly predicted problem-focused coping, and femininity
      significantly predicted emotion-focused coping. Further, the levels of family and
      college stress reported by college students, as well as their endorsement of
      avoidant coping, significantly predicted their levels of depressive symptoms.
      Overall, the results of this study suggest that understanding the relationships
      among the gender role, the levels of depressive symptomatology, and the levels of
      stress exhibited by college freshmen may be important in facilitating their
      transition and adjustment to university life.

PMID- 16810672
TI  - Chromosome condensation outside of mitosis: mechanisms and new tools.
AB  - A basic principle of cell physiology is that chromosomes condense during mitosis.
      However, condensation can be uncoupled from mitotic events under certain
      circumstances. This phenomenon is known as "premature chromosome condensation
      (PCC)." PCC provides insights in the mechanisms of chromosome condensation, thus
      helping clarifying the key molecular events leading to the mitosis. Besides, PCC
      has proved to be an useful tool for analyzing chromosomes in interphase. For
      example, using PCC we can visualize genetic damage shortly after the exposure to
      clastogenic agents. More than 30 years ago, the first report of PCC in interphase
      cells fused to mitotic cells using Sendai virus was described (virus-mediated
      PCC). The method paved the way to a great number of fundamental discoveries in
      cytogenetics, radiation biology, and related fields, but it has been hampered by
      technical difficulties. The novel drug-induced PCC method was introduced about 10
      years ago. While fusion-induced PCC exploits the action of external
      maturation/mitosis promoting factor (MPF), migrating from the inducer mitotic
      cell to the interphase recipient, drug-induced PCC exploits protein phosphatase
      inhibitors, which can activate endogenous intracellular MPF. This method is much
      simpler than fusion-induced PCC, and has already proven useful in different
      fields.

PMID- 16810673
TI  - Deep brain stimulation for Parkinson's disease: surgical issues.
AB  - Numerous factors need to be taken into account when implanting deep brain
      stimulation (DBS) systems into patients with Parkinson's disease. The surgical
      procedure itself can be divided into immediate preoperative, intraoperative, and
      immediate postoperative phases. Preoperative considerations include medication
      withdrawal issues, stereotactic equipment choices, imaging modalities, and
      targeting strategy. Intraoperative considerations focus on methods for
      physiological confirmation of a given target for DBS electrode deployment. Terms
      such as microelectrode recording, microstimulation, and macrostimulation will be
      defined to clarify inconsistencies in the literature. Advantages and
      disadvantages of each technique will be addressed. Furthermore, operative
      decisions such as staging, choice of electrode and implantable pulse generator,
      and methods of device fixation will be outlined. Postoperative issues include
      imaging considerations, including magnetic resonance safety, device-device
      interactions, and immediate surgical complications pertaining to the DBS
      procedure. This report outlines answers to a series of questions developed to
      address all aspects of the DBS surgical procedure and decision-making with a
      systematic overview of the literature (until mid-2004) and by the expert opinion
      of the authors. This is a report from the Consensus on Deep Brain Stimulation for
      Parkinson's Disease, a project commissioned by the Congress of Neurological
      Surgeons and the Movement Disorder Society. It outlines answers to a series of
      questions developed to address all surgical aspects of deep brain stimulation.

PMID- 16810674
TI  - Anatomy and physiology of the basal ganglia: implications for deep brain
      stimulation for Parkinson's disease.
AB  - Central to surgical management of movement disorders is an understanding of the
      anatomy and physiology of the basal ganglia. The basal ganglia have been a target
      for neuromodulation surgery since Russell Meyers' pioneering works in the late
      1930s. With the development of deep brain stimulation as the gold standard of
      surgical intervention for movement disorders, there has been a concomitant
      evolution in the understanding of the role the basal ganglia plays in the genesis
      of normal and abnormal motor behaviors. The fundamental concept of the cortico
      striato-pallido-thalamocortical loop will be explored in the context of deep
      brain stimulation. The current targets for deep brain stimulation for Parkinson's
      disease, the subthalamic nucleus, the globus pallidus internus, and the ventral
      intermediate nucleus, will be discussed in the framework of the current
      physiological and anatomical models of Parkinson's disease (PD). Finally, the
      current understandings of the mechanisms underpinning the beneficial effects of
      deep brain stimulation for PD will be discussed.

PMID- 16810675
TI  - Basic algorithms for the programming of deep brain stimulation in Parkinson's
      disease.
AB  - The clinical success of deep brain stimulation (DBS) for treating Parkinson's
      disease (PD) critically depends on the quality of postoperative neurological
      management. Movement disorder specialists becoming involved with this therapy
      need to acquire new skills to adapt optimally stimulation parameters and
      medication after implantation of a DBS system. At first glance, the infinite
      number of theoretically possible parameter combinations seems to make programming
      a complex and time-consuming art. This article outlines a stepwise and
      standardized approach, reducing the possible parameter settings in DBS to a few
      relevant combinations. The basic programming algorithms for thalamic,
      subthalamic, and pallidal stimulation in PD are explained and summarized in
      flowcharts.

PMID- 16810676
TI  - Deep brain stimulation: neuropsychological and neuropsychiatric issues.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor,
      cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. The efficacy
      of deep brain stimulation (DBS) for the motor symptoms of advanced PD is well
      established. However, the effects of DBS on the cognitive and neuropsychiatric
      symptoms are less clear. The neuropsychiatric aspects of DBS for PD have recently
      been of considerable clinical and pathophysiological interest. As a companion to
      the preoperative and postoperative sections of the DBS consensus articles, this
      article reviews the published literature on the cognitive and neuropsychiatric
      aspects of DBS for PD. The majority of the observed neuropsychiatric symptoms are
      transient, treatable, and potentially preventable. Outcome studies,
      methodological issues, pathophysiology, and preoperative and postoperative
      management of the cognitive and neuropsychiatric aspects and complications of DBS
      for PD are discussed.

PMID- 16810678
TI  - Mutation of the SNF2 family member Chd2 affects mouse development and survival.
AB  - The chromodomain helicase DNA-binding domain (Chd) proteins belong to the SNF2
      like family of ATPases that function in chromatin remodeling and assembly. These
      proteins are characterized by the presence of tandem chromodomains and are
      further subdivided based on the presence or absence of additional structural
      motifs. The Chd1-Chd2 subfamily is distinguished by the presence of a DNA-binding
      domain that recognizes AT-rich sequence. Currently, there are no reports
      addressing the function of the Chd2 family member. Embryonic stem cells
      containing a retroviral gene-trap inserted at the Chd2 locus were utilized to
      generate mice expressing a Chd2 protein lacking the DNA-binding domain. This
      mutation in Chd2 resulted in a general growth delay in homozygous mutants late in
      embryogenesis and in perinatal lethality. Animals heterozygous for the mutation
      showed decreased neonatal viability and increased susceptibility to non
      neoplastic lesions affecting most primary organs. In particular, approximately
      85% of the heterozygotes showed gross kidney abnormalities. Our results
      demonstrate that mutation of Chd2 dramatically affects mammalian development and
      long-term survival.

PMID- 16810679
TI  - Mutation analysis of the GNE gene in distal myopathy with rimmed vacuoles (DMRV)
      patients in Thailand.
AB  - Distal myopathy with rimmed vacuoles (DMRV) is an early-adult-onset, distal
      myopathy caused by a mutation of the UDP-N-acetylglucosamine 2 epimerase/N
      acetylmannosamine kinase (GNE) gene. We herein report four Thai patients with
      DMRV who carried compound heterozygous mutations of the GNE gene including three
      novel (p.G89R, p.P511T, and p.I656N) and two known mutations (p.A524V and
      p.V696M). All patients shared p.V696M in one allele. Our study demonstrates the
      mutation spectrum of the GNE gene in Thai patients with DMRV.

PMID- 16810681
TI  - Developmental regulation of biglycan expression in muscle and tendon.
AB  - Biglycan is an extracellular ligand for the dystrophin-associated protein complex
      (DAPC) that is upregulated in both dystrophic and regenerating muscle. Biglycan
      also binds to collagen VI, mutations of which cause a congenital muscular
      dystrophy (Ullrich's; UCMD) that is also characterized by connective tissue
      abnormalities. The expression of biglycan in early development and postnatal ages
      has not been well characterized. Here we show that biglycan transcript levels
      peak at approximately 21 weeks' gestation in human fetal muscle.
      Immunocytochemical analysis of developing mouse muscle shows that biglycan can be
      detected in muscle as early as embryonic day (E)16 and is most abundant between
      postnatal day (P)1 and P7. Biglycan is also highly expressed in developing
      tendon, with maximal levels observed at E16-18. This robust tendon expression is
      correlated with a sharp peak in biglycan transcript levels in the hindlimb.
      Finally, at E18 collagen VI colocalizes with biglycan in tendon. These results
      suggest that biglycan has a particularly important function during muscle and
      connective tissue development. Moreover, biglycan may play a role in the
      pathogenesis of collagen VI-associated congenital muscular dystrophies.

PMID- 16810680
TI  - CK-MM autoantibodies: prevalence, immune complexes, and effect on CK clearance.
AB  - Although the blood level of creatine kinase (CK) is the most commonly used marker
      of muscle injury, there is marked interindividual variability in this measure.
      Part of this variability may be attributed to variability in the rate of CK
      clearance from the circulation. In this study, we assessed the possibility that
      CK-MM autoantibodies form immune complexes with CK following muscle injury and
      subsequently affect the CK clearance rate. Using an enzyme-linked immunosorbent
      assay, CK-MM autoantibodies were detected in all 25 human subjects studied but
      the levels varied greatly. Using protein A-sepharose, the percentage of the
      plasma CK activity found in immune complexes was determined to be correlated with
      the CK-MM autoantibody level at lower CK levels (<1,022 U/L). When CK-MM
      antibodies were administered to mice, plasma CK activity following a bolus CK
      injection was reduced by 11%-32%. We conclude that CK-MM autoantibodies can
      modulate the rate of CK clearance from the circulation. Thus, the relatively low
      blood CK levels seen in some individuals following injury may be attributed
      partly or entirely to an autoantibody-enhanced clearance of CK.

PMID- 16810682
TI  - Neoplastic lumbosacral radiculoplexopathy in prostate cancer by direct perineural
      spread: an unusual entity.
AB  - Neoplastic lumbosacral plexopathy occurs with some abdominal and pelvic
      malignancies. Patients present with severe pain radiating from the low back down
      to the lower extremities, and this progresses to weakness. Neoplastic lumbosacral
      plexopathy is virtually always associated with known malignancy or obvious pelvic
      metastatic disease. Uncommonly, prostate cancer can present as a lumbosacral
      plexopathy occurring through direct pelvic spread. We describe two cases of
      lumbosacral radiculoplexopathy from infiltrative prostate cancer without evidence
      of other pelvic or extraprostatic spread. The probable etiology of tumor
      spreading along prostatic nerves into the lumbosacral plexus (i.e., perineural
      spread) is discussed as are the potential mechanisms for this unusual mode of
      cancer dissemination.

PMID- 16810684
TI  - Approaches to the treatment of mitochondrial diseases.
AB  - Therapy for mitochondrial diseases is woefully inadequate. However, lack of a
      cure does not equate with lack of treatment. Palliative therapy is dictated by
      good medical practice and includes anticonvulsant medication, control of
      endocrine dysfunction, and surgical procedures. Removal of noxious metabolites is
      centered on combating lactic acidosis, but extends to other metabolites. Attempts
      to bypass blocks in the respiratory chain by administration of electron acceptors
      have not been successful, but this may be amenable to genetic engineering.
      Administration of metabolites and cofactors is the mainstay of real-life therapy
      and is especially important in disorders due to primary deficiencies of specific
      compounds, such as carnitine or coenzyme Q10 (CoQ10). There is increasing
      interest in the administration of reactive oxygen radicals (ROS) scavengers, both
      in primary mitochondrial diseases and in neurodegenerative diseases. Gene therapy
      is a challenge because of polyplasmy and heteroplasmy, but novel experimental
      approaches are being pursued. One important strategy is to decrease the ratio of
      mutant to wild-type mitochondrial genomes ("gene shifting") by different means:
      (1) converting mutated mitochondrial DNA (mtDNA) genes into normal nuclear DNA
      genes ("allotopic expression"); (2) importing cognate genes from other species
      ("xenotopic expression"); (3) correcting mtDNA mutations by importing specific
      restriction endonucleases; (4) selecting for respiratory function; and (5)
      inducing muscle regeneration. Germline therapy raises ethical problems but is
      being considered for prevention of maternal transmission of mtDNA mutations.
      Preventive therapy through genetic counseling and prenatal diagnosis is becoming
      increasingly important for nuclear DNA-related disorders.

PMID- 16810683
TI  - KDI tripeptide of gamma1 laminin protects rat dopaminergic neurons from 6-OHDA
      induced toxicity.
AB  - Our previous studies indicate that the KDI (Lys-Asp-Ile) tripeptide of gamma1
      laminin protects central neurons from mechanical trauma and excitotoxicity. At
      least part of the neuroprotective effect of the KDI tripeptide may be mediated by
      its inhibitory function on ionotropic glutamate receptors. We studied the
      protective effect of the KDI tripeptide against 6-hydroxy-dopamine (6-OHDA)
      induced neurotoxicity in a rat experimental model of Parkinson's disease (PD). We
      found that a single unilateral injection of the KDI tripeptide into the
      substantia nigra before an injection of 6-OHDA protected the dopaminergic neurons
      from the neurotoxicity of 6-OHDA. Compared to rats treated with 6-OHDA alone, the
      KDI + 6-OHDA-treated substantia nigra was relatively intact with large numbers of
      dopaminergic neurons present at the injection side. In the rats treated with 6
      OHDA alone, no dopaminergic neurons were detected, and the substantia nigra-area
      at the injection side was filled with blood-containing cavities. Quantification
      of the rescue effect of the KDI tripeptide indicated that, in animals receiving
      KDI before 6-OHDA, 33% of tyrosine hydroxylase-positive dopaminergic neurons of
      the substantia nigra were present as compared to the contralateral non-injected
      side. In animals receiving 6-OHDA alone, only 1.4% of the tyrosine hydroxylase
      expressing dopaminergic neurons could be verified. If this much protection were
      achieved in humans, it would be sufficient to diminish or greatly alleviate the
      clinical symptoms of PD. We propose that the KDI tripeptide or its derivatives
      might offer a neuroprotective biological alternative for treatment of PD.

PMID- 16810685
TI  - Matrix metalloproteinases are involved in mechanical stretch-induced activation
      of skeletal muscle satellite cells.
AB  - When skeletal muscle is stretched or injured, myogenic satellite cells are
      activated to enter the cell cycle. This process depends on nitric oxide (NO)
      production, release of hepatocyte growth factor (HGF) from the extracellular
      matrix, and presentation of HGF to the c-met receptor. Experiments reported
      herein provide new evidence that matrix metalloproteinases (MMPs) are involved in
      the NO-dependent release of HGF in vitro. When rat satellite cells were treated
      with 10 ng/ml recombinant tissue inhibitor-1 of MMPs (TIMP-1) and subjected to
      treatments that induce activation in vitro, i.e., sodium nitroprusside (SNP) of
      an NO donor or mechanical cyclic stretch, the activation response was inhibited.
      In addition, conditioned medium generated by cultures treated with TIMP-1 plus
      SNP or mechanical stretch failed to activate cultured satellite cells and did not
      contain HGF. Moreover, NO(x) assay demonstrated that TIMP-1 does not impair NO
      synthase activity of stretched satellite cell cultures. Therefore, results from
      these experiments provide strong evidence that MMPs mediate HGF release from the
      matrix and that this step in the pathway is downstream from NO synthesis.

PMID- 16810686
TI  - Sour on the inside, calm on the outside: how acetazolamide may stabilize membrane
      excitability.

PMID- 16810688
TI  - Statin myopathy: the iceberg or its tip?

PMID- 16810687
TI  - P2 purinergic receptors signal to glycogen synthase kinase-3beta in astrocytes.
AB  - Glycogen synthase kinase (GSK)-3 was identified initially as an enzyme that
      regulates glycogen synthesis in response to insulin, but more recent studies
      indicate that it is also involved in numerous cellular processes, including cell
      survival, cell cycle regulation, proliferation, and differentiation. Because
      extracellular ATP exerts trophic actions on astrocytes, we investigated a
      possible signaling linkage from P2 purinergic receptors to GSK3beta. Addition of
      ATP to primary cultures of rat cortical astrocytes resulted in phosphorylation of
      Ser9 on GSK3beta and a concomitant decrease in GSK3 activity. UTP and 2',3'-O-(4
      benzoyl)-benzoyl ATP (BzATP) increased phosphorylation of Ser9 on GSK3beta
      indicating that metabotropic P2Y and ionotropic P2X receptors are coupled to
      GSK3beta. Signaling studies showed that phosphorylation of Ser9-GSK3beta in
      response to ATP was inhibited by downregulation of protein kinase C (PKC) but not
      by blockade of Akt or p70 S6 kinase pathways. PKC also links P2 receptors to ERK
      in astrocytes, but inhibition of ERK signaling did not block phosphorylation of
      Ser9-GSK3beta stimulated by P2 receptors. Mechanical strain, which releases ATP,
      also stimulated Ser9 phosphorylation and this was attenuated by hydrolysis of
      extracellular ATP with apyrase or by blockade of P2 receptors. We conclude that
      P2 receptors are coupled to GSK3beta by a PKC-dependent pathway that is
      independent of Akt, p70 S6 kinase, and ERK pathways. These findings suggest that
      purinergic signaling contributes to the regulation of GSK3beta functions, one of
      which may be the response of astrocytes to CNS injury on release of ATP.

PMID- 16810689
TI  - Differences of the ipsilateral silent period in small hand muscles.
AB  - The ipsilateral silent period (iSP) is thought to depend on activity transmitted
      by the corpus callosum but ipsilateral corticospinal pathways may also
      contribute. Because the presence of ipsilateral corticospinal pathways differs
      between small hand muscles, we compared the iSP in the first dorsal interosseous
      (FDI) and abductor pollicis brevis (APB) muscles. The iSP was elicited in 20
      healthy subjects by focal transcranial magnetic stimulation of one primary motor
      cortex during maximal voluntary contraction of the ipsilateral target muscle. The
      iSP duration was significantly longer in the FDI than APB because of an
      irregularly occurring second phase of inhibition in the FDI that was absent in
      the APB. Although the first phase of inhibition is transmitted by the corpus
      callosum, we provide evidence that the second phase is mediated through
      ipsilateral corticospinal pathways. Therefore, for specific assessment of
      callosal conduction, the iSP should be measured in the APB rather than FDI.

PMID- 16810690
TI  - Long-term effects of JL 13, a potential atypical antipsychotic, on rat dopamine
      and serotonin receptor subtypes.
AB  - Changes in dopamine (DA) D(1), D(2), D(3), and D(4) receptors and serotonin 5
      HT(1A) and 5-HT(2A) receptors in rat forebrain regions were autoradiographically
      quantified after continuous infusion of JL 13 [(5-(4-methylpiperazin-1-yl)-8
      chloro-pyrido[2,3-b][1,5]benzoxazepine fumarate] for 28 days with osmotic
      minipumps and compared with the effects of other typical (fluphenazine) and
      atypical (clozapine, olanzapine, and risperidone) antipsychotic drugs from
      previous studies. Similar to other typical and atypical antipsychotics, JL 13
      increased labeling of D(2) receptors in medial prefrontal cortex (MPC) and
      hippocampus (HIP) and D(4) receptors in nucleus accumbens (NAc), caudate-putamen
      (CPu), and HIP. In addition, JL 13 increased 5-HT(1A) and decreased 5-HT(2A)
      receptors in MPC and dorsolateral frontal cortex (DFC), an effect shared by
      atypical antipsychotics, and may contribute to their psychopharmacological
      properties. Clozapine and JL 13, but not other antipsychotics, spared D(2)
      receptors in CPu, which may reflect their ability to induce minimal
      extrapyramidal side effects. In addition, JL 13 but not other typical and
      atypical antipsychotic drugs increased abundance of D(1) receptors in CPu and
      NAc. JL 13 as well as other antipsychotic agents did not alter levels of
      forebrain D(3) receptors. An atypical-like profile of JL 13 on DA and 5-HT
      receptor subtypes should encourage further development of this compound as a
      novel atypical antipsychotic drug.

PMID- 16810691
TI  - Exercise intolerance associated with a novel 8300T > C mutation in mitochondrial
      transfer RNAlys.
AB  - Mutations in the mitochondrial genome contribute to the pathophysiology of many
      neuromuscular diseases. Recently there has been an increased appreciation of the
      role of mitochondrial DNA (mtDNA) mutations in the etiology of exercise
      intolerance. Using TTGE (temporal temperature-gradient gel electrophoresis) and
      sequence analyses of the entire mitochondrial genome, we identified a novel
      heteroplasmic mutation (8300T > C) in the tRNAlys gene (MTTK) from a patient with
      unexplained exercise intolerance. The mutation was present in blood, hair, and
      muscle, with the highest percentage of heteroplasmy found in muscle. The results
      of muscle respiratory chain enzyme analysis are consistent with tRNA mutation.
      These data suggest that this novel mutation is yet another mtDNA mutation
      associated with muscle disease and should be considered in patients with similar
      symptoms.

PMID- 16810692
TI  - What is the origin of the premotor potential recorded from the second lumbrical?
AB  - When recording with a palm electrode, a premotor potential (PMP) precedes the
      compound muscle action potential that is evoked from the second lumbrical muscle
      following median nerve stimulation. The origin of this PMP has been uncertain. We
      demonstrate that median sensory nerve action potentials (SNAPs) can be recorded
      orthodromically with the palm electrode and conclude that the origin of the PMP
      is a median SNAP arising from antidromically activated digital sensory branches.

PMID- 16810693
TI  - Survey of electrodiagnostic laboratories regarding hemorrhagic complications from
      needle electromyography.
AB  - Little is known about the complications of needle electromyography (EMG)
      performed on anticoagulated patients, and no guidelines exist regarding its
      performance. We conducted an anonymous survey of academic EMG laboratories in the
      U.S. to understand current practices and complications with regard to
      anticoagulated patients and those receiving antiplatelet medications. Forty-seven
      (78%) of 60 EMG laboratories responded to the survey. Four laboratories (9%)
      reported at least one hemorrhagic complication requiring medical or surgical
      intervention in an anticoagulated patient, whereas none reported a hemorrhagic
      complication in patients receiving antiplatelet medications. Ten (21%) reported
      willingness to evaluate cranial, paraspinal, and all limb muscles in
      anticoagulated patients. This survey suggests that hemorrhagic complications from
      needle EMG of anticoagulated patients are rare. It also suggests that needle EMG
      of patients receiving antiplatelet therapy is not associated with increased
      reports of hemorrhagic complications.

PMID- 16810694
TI  - Peak power of muscles injured by lengthening contractions.
AB  - Excessive or extreme lengthening contractions have a well-characterized
      depressive effect on skeletal muscle isometric force. In addition to producing
      force, active muscles must often shorten in order to meet the power requirements
      of locomotion and other physical activities. However, the impact of lengthening
      contractions on muscle power is poorly understood. We evaluated the effect of 20
      isometric contractions or 20 lengthening contractions (20% strain at 1.5 fiber
      lengths/s) on the force-velocity-power relationships of mouse soleus muscles in
      vitro at 35 degrees C. Pre- and posttreatment data were obtained as the muscles
      shortened through their optimal length (Lo). The isometric treatment did not
      alter Lo, the curvature of the force-velocity relationship (a/Po), or soleus
      maximal shortening velocity (Vmax), whereas peak force (Po) displayed a slow,
      time-dependent decline of 10% across the experiments. Following the lengthening
      treatment, Lo increased by 6%, a/Po increased by 22%, and Vmax and Po fell by 24%
      and 26%, respectively. Under optimal conditions for producing power, muscles
      damaged by lengthening contractions attained 22% less force and shortened 20%
      more slowly than before damage. Consequently, soleus peak power fell 37% after
      lengthening, a 2.5-fold greater decline than noted for the isometric treatment.
      Under the conditions studied here, the excessive power loss following lengthening
      contractions was due to force and velocity deficits of approximately equal
      relative magnitude. Because power represents the ability of the muscle to perform
      work, reductions in both force and shortening velocity should be considered when
      evaluating and treating lengthening-induced skeletal muscle injuries.

PMID- 16810695
TI  - Impaired abdominal muscle contractility after high-intensity exhaustive exercise
      assessed by magnetic stimulation.
AB  - High-intensity exercise can induce diaphragm fatigue which can, in turn, limit
      exercise performance. We investigated whether expiratory muscles fatigue
      similarly during exhaustive exercise. Eleven healthy male volunteers cycled to
      exhaustion at 85% maximal power. Before, immediately after exercise, and after 30
      and 60 min of recovery, the nerve roots supplying the abdominal muscles were
      stimulated magnetically at the T10 level in the prone position after full
      potentiation. Twitch gastric pressure (Pga,tw) was simultaneously recorded. After
      cycling, Pga,tw was significantly reduced compared to before exercise (40.2 +/-
      6.6 vs. 45.3 +/- 7.5 cmH2O; P < 0.001), whereas after 30 and 60 min of recovery
      differences were no longer significant. The reduction in Pga,tw directly after
      exercise correlated neither with the fitness level nor with abdominal muscle
      work, respiratory sensations, or blood lactate concentration during exercise.
      These results indicate that the ventilatory requirements during intensive
      exercise can impair abdominal muscle contractility similar to diaphragmatic
      contractility. Thus, abdominal muscle fatigue may also contribute to exercise
      limitation, especially when expiratory resistance is increased as in patients
      with chronic obstructive pulmonary disease.

PMID- 16810696
TI  - Fast automatic linear off-resonance correction method for spiral imaging.
AB  - Field inhomogeneity and susceptibility variations, coupled with a long readout,
      can result in image blurring in spiral imaging. Many correction methods based on
      a priori off-resonance information, such as an acquired field map, have been
      proposed in the literature. Automatic off-resonance correction methods are
      alternative approaches that estimate a field map from the image data themselves.
      In this paper we propose a fast automatic off-resonance correction method that
      performs linear correction without acquiring a field map. The method requires
      only about two times the total computation time compared to image reconstruction
      by gridding. It can also be used in combination with a full field map automatic
      off-resonance correction method to increase the extent of correction. The method
      is demonstrated by in vivo coronary artery imaging.

PMID- 16810697
TI  - Competition of nitroxyl contrast agents as an in vivo tissue redox probe:
      comparison of pharmacokinetics by the bile flow monitoring (BFM) and blood
      circulating monitoring (BCM) methods using X-band EPR and simulation of decay
      profiles.
AB  - Nitroxyl radicals used as tissue redox-sensitive contrast agents in electron
      paramagnetic resonance (EPR) and/or NMR imaging should satisfy the following two
      conditions: 1) the molecules disperse into tissues rapidly, and 2) paramagnetic
      loss occurs by simple reduction of the radical. The pharmacokinetic trends of
      several nitroxyl contrast agents were compared with the results obtained by bile
      flow monitoring (BFM) and blood circulation monitoring (BCM) methods using X-band
      EPR. The nitroxyl radicals (TEMPO, TEMPONE (oxo-TEMPO), and amino-TEMPO) showed
      additional EPR signals in the bile that were attributed to metabolites formed
      during transport from blood to bile through the liver. However, the highly
      hydrophilic CAT-1 (trimethylammonium-TEMPO), which has low membrane permeability,
      showed minimal concentration in the bile. Probes that have carboxyl moiety, such
      as carboxy-TEMPO and carboxy-PROXYL, can be transported via anion transporter
      into hepatic cells. The EPR signal decay profiles of the nitroxyl radicals were
      simulated based on the experimental data. The simulation, which we previously
      applied to mouse blood, was modified to simultaneously fit the experimental
      results of BFM and BCM obtained with rats. The simulation data showed the
      simplicity/complexity of the pharmacokinetic mechanisms and that carbamoyl-PROXYL
      and TEMPOL (hydroxy-TEMPO) are suitable contrast agents for assessing tissue
      redox status.

PMID- 16810698
TI  - Long-term effects of novel biolimus eluting DEVAX AXXESS plus nitinol self
      expanding stent in a porcine coronary model.
AB  - OBJECTIVE: The purpose of this study was to evaluate the long-term effects of the
      DEVAX AXXESS biolimus eluting stent (BES) in a porcine coronary model, compared
      with those of bare metal stent (BMS) and polymer only stent (POS) controls.
      BACKGROUND: Excessive neointimal growth has been identified as a major cause of
      late failure of percutaneous coronary interventions. The effect of drug eluting
      from self-expanding stents for prevention of neointimal hyperplasia has not been
      studied before. The DEVAX AXXESS is a self-expanding nickel titanium stent,
      coated with antiproliferative compound-biolimus. METHODS: Twenty juvenile farm
      swine, 25-35 kg in weight, 3-6 months in age were used. Each animal received a
      stent to the left anterior descending artery, left circumflex or right coronary
      arteries as permitted per anatomy. The chronic vascular response after BES
      implantation was compared with that after BMS and POS implantation at 28, 90, and
      180 days follow-up. RESULTS: The 28-day outcome by quantitative coronary
      angiography (QCA) showed significant increase in minimal luminal diameter (MLD)
      in the BES (MLD: 2.90 +/- 0.97, 2.39 +/- 0.90, 1.59 +/- 0.91; P = 0.009) compared
      with BMS and POS, respectively. By histomorphometric analysis, there was also a
      corresponding significant reduction in neointimal tissue proliferation in the BES
      (average neointimal area: 2.78 +/- 0.07, 5.46 +/- 0.66, 8.42 +/- 0.85; P = 0.002)
      compared with that in BMS and POS controls, respectively at 28-days follow-up. At
      90 and 180 days, the mean neointimal area was not significantly different between
      the BES and the controls. CONCLUSIONS: BES favorably modulates the neointimal
      tissue formation for 28 days, in the porcine coronary model. Long-term inhibition
      of neointimal hyperplasia is not sustained most likely because of the delayed
      cellular proliferation and inflammation in the vessel wall.

PMID- 16810699
TI  - Radiation following percutaneous balloon aortic valvuloplasty to prevent
      restenosis (RADAR pilot trial).
AB  - OBJECTIVES: We wished to determine the feasibility and early safety of external
      beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV)
      to prevent restenosis. BACKGROUND: BAV for calcific aortic stenosis (AS) has been
      largely abandoned because of high restenosis rates, i.e., > 80% at 1 year.
      Radiation therapy is useful in preventing restenosis following vascular
      interventions and treating other benign noncardiovascular disorders. METHODS: We
      conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis
      following BAV in elderly patients with calcific AS. Total doses ranging from 12
      18 Gy were delivered in fractions over a 3-5 day post-op period to the aortic
      valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months
      following BAV. RESULTS: One-year follow-up is completed (age 89 +/- 4). There
      were no complications related to EBRT. Eight patients died prior to 1 year; 5 of
      10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15-18
      Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the
      initial AVA gain, and only three deaths were cardiac in origin. One patient
      underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the
      initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group
      demonstrated restenosis (21% overall). CONCLUSIONS: EBRT following BAV in elderly
      patients with AS is feasible, free of early complications, and holds promise in
      reducing the 1 year restenosis rate in a dose-dependent fashion.

PMID- 16810700
TI  - Double balloon pulmonary valvuloplasty: multi-track system versus conventional
      technique.
AB  - OBJECTIVES: To evaluate whether double balloon pulmonary valvuloplasty (DBPV)
      with the Multi-Track system (MTS) may help to simplify the procedure. BACKGROUND:
      DBPV is usually required for patients with pulmonary valve stenosis with large
      annulus. However, it needs two venous accesses and can be technically demanding.
      METHODS: From 07/03, 20 consecutive patients (19 +/- 10 yrs) with typical
      pulmonary valve stenosis underwent DBPV using the MTS (G1). The results were
      compared with those achieved by conventional DBPV performed in a matched
      historical group of 28 patients (21 +/- 11 yrs; P = NS) (G2). RESULTS: MTS
      balloons were easily advanced through the skin and inflated across the valve.
      Similar results were observed in regards to residual gradients (12 +/- 11 vs 14
      +/- 10 mm Hg; P = NS) and right ventricular to systemic pressures (0.35 +/- 0.22
      vs 0.37 +/- 0.26; P = NS). Procedure and fluoroscopic times were significant
      lower in G1 (78 +/- 24 vs 126 +/- 28; 15 +/- 12 vs 25 +/- 8 min, respectively;
      both P < 0.001). There was no major complication. Median follow-up was 1.8 yr for
      G1 and 5 yr for G2 (P = 0.037). At the last visit, peak instantaneous gradient
      across the right ventricular outflow tract by echocardiography was a mean 22 +/-
      10 mm Hg for G1 and 25 +/- 9 mm Hg for G2 (P = NS). No patient had severe
      pulmonary insufficiency or required reintervention. CONCLUSIONS: The use of the
      MTS helped to expedite the procedure providing satisfactory midterm clinical
      outcomes, similar to those observed with the conventional DBPV technique.

PMID- 16810701
TI  - Rapid pacing to facilitate transcatheter prosthetic heart valve implantation.
AB  - OBJECTIVES: We describe the technique of, and our experience with, rapid
      ventricular burst pacing to facilitate transcatheter heart valve implantation.
      BACKGROUND: Endovascular therapeutic procedures frequently require the precise
      placement of implantable devices. The precision of transcatheter device
      deployment may be hampered by cardiac motion or the effects of intravascular
      flow. Burst pacing is associated with a reduction in stroke volume, cardiac
      output, transvalvular flow, and cardiac motion. METHODS: Rapid pacing was used in
      40 consecutive patients with severe aortic stenosis undergoing implantation of
      catheter-delivered prosthetic valves. Clinical, procedural, and hemodynamic
      records were reviewed. RESULTS: A mean of 5 +/- 2 burst pacing sequences at rates
      of 150-220 min(-) (1) were used during balloon valvuloplasty and valve
      deployment. The duration of pacing required during valve deployment was 12 +/- 3
      sec. Pacing was relatively well tolerated when cautiously used with judicious
      recovery intervals and pressor support. Rapid pacing was associated with a rapid
      and effective reduction in systemic blood pressure, pulse pressure, transvalvular
      flow as well as cardiac and catheter motion. CONCLUSIONS: Rapid pacing is a
      relatively reliable technique to facilitate precise transcatheter deployment of
      prosthetic heart valves and other endovascular therapeutic devices.

PMID- 16810703
TI  - Detection of reactive free radicals derived from nucleosides by liquid
      chromatography coupled to tandem mass spectrometry of DMPO spin trapping adducts.
AB  - In this study, reactive free radicals derived from several nucleosides were spin
      trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and then detected by high
      performance liquid chromatography coupled to electrospray ionization tandem mass
      spectrometry (HPLC/ESI-MS/MS). This method provides a specific detection of spin
      trapping adducts derived from nucleosides with a very high sensitivity:
      quantities as low as 0.5 picomoles of spin trapping adducts corresponding to
      concentrations of 2.5 10(-8) mol . L(-1) were detected. Different spin trapping
      adducts were characterized by HPLC/ESI-MS/MS in three well-known systems
      producing free radicals photochemically: the photolysis of 5-halo-2'
      deoxyuridines, the photolysis of 5-thiophenylmethyl-2'-deoxyuridine and the
      photolysis of thymidine with menadione bisulfite as a photosensitizer. A new
      radical photoreactivity of uridine derivatives was also detected by this method
      both at the nucleoside and at the RNA level, showing that the method is also
      relevant for studying spin trapping adducts derived from DNA and RNA strands.

PMID- 16810702
TI  - HUVECs from newborns with a strong family history of diabetes show diminished ROS
      synthesis in the presence of high glucose concentrations.
AB  - BACKGROUND: A family history of type 2 diabetes mellitus (DM) increases the
      probability to develop DM and endothelial dysfunction. The probable mechanism
      involves augmented reactive oxygen species (ROS) synthesis. The aim of this study
      was to evaluate the synthesis of ROS in human umbilical vein endothelial cells
      (HUVECs) obtained from healthy newborns with (experimental) and without (control)
      a strong family history of type 2 DM, exposed to different glucose
      concentrations. METHODS: HUVECs were exposed to various glucose concentrations
      for 24 and 48 h periods, before cell proliferation, mitochondrial activity, and
      mitochondrial membrane potential were determined. Intracellular ROS synthesis in
      the presence or absence of the mitochondrial uncoupler CCCP, cytochalasin B, or
      diphenyleneiodonium (DPI) was also evaluated. RESULTS: As opposed to control
      HUVECs, we found that experimental HUVECs exposed to 30 mmol/L glucose showed a
      50% decrease in cell proliferation, a 90% reduction in mitochondrial activity,
      and a statistically significant inhibition of ROS synthesis in the presence of
      CCCP or cytochalasin B; DPI had no effect. CONCLUSIONS: Our results suggest that
      mitochondria and NAD(P)H-oxidase from HUVECs obtained from healthy newborns with
      a family history of DM have an innate deficient response to high glucose
      concentrations.

PMID- 16810704
TI  - Investigation of the ionisation and fragmentation behaviour of different
      nitroaromatic compounds occurring as polar metabolites of explosives using
      electrospray ionisation tandem mass spectrometry.
AB  - In order to develop a liquid chromatography/electrospray ionisation tandem mass
      spectrometry (LC/ESI-MS/MS) method for identification and quantification of polar
      metabolites of explosives using a triple quadrupole system, the mass
      spectrometric ionisation and fragmentation behaviour of different nitrophenols,
      nitro- and aminonitrobenzoic acids, nitrotoluenesulfonic acids, and
      aminonitrotoluenes was investigated. Due to their different molecular structures,
      the substances concerned showed a very different ionisation efficiency in the ESI
      process. Interestingly, 2,4-dinitrobenzoic acid yielded no mass signals in the Q1
      scan suggesting a thermal decarboxylation in the ion source, whereas the
      corresponding 3,5-isomer showed a high ionisation yield. Using negative
      ionisation polarity, carboxylic, phenolic, and sulfonic acid groups were
      deprotonated resulting in molecular anions, which could be fragmented in a
      collision cell. A pronounced dependency of the produced fragment ion series on
      the kind and position of substituents at the nitrobenzene ring (ortho effects)
      was observed and exploited for the development of substance-specific detection
      methods in the multiple reaction monitoring mode. In case of benzoic and sulfonic
      acids, decarboxylation and desulfonation, respectively, were observed as the most
      frequent fragmentation reactions. Furthermore, besides loss of NO(2), NO
      fragmentation occurred and preceded a decarbonylation of the benzene ring. The
      expulsion of the open-shell molecules NO and NO(2) led to a variety of distonic
      radical anions.

PMID- 16810705
TI  - Novel applications of highly sensitive liquid chromatography/mass
      spectrometry/mass spectrometry for the direct detection of ultra-trace levels of
      contaminants in water.
AB  - Recent advances in the sensitivity of liquid chromatography/mass spectrometry
      (LC/MS) instrument technology provide the basis for the direct detection, i.e.
      without sample pre-concentration, of organic contaminants in water in the ng/L
      range. Novel applications for the analysis of atrazine and some of its
      desalkylated and hydroxylated degradation products, the pharmaceutical compounds
      diclofenac and carbamazepine, sulfonylurea herbicides, and iodinated X-ray
      contrast media have been developed. For each analyte a specific tandem mass
      spectrometric (MS/MS) transition has been selected and the corresponding mass
      spectrometric parameters optimised. All analytes could be analysed within three
      specific analytical runs including different high-performance liquid
      chromatography (HPLC) conditions. Detection limits were determined to be better
      than 10 ng/L for the direct analysis of the compounds in water except for X-ray
      contrast media, for which detection limits were found to be up to one order of
      magnitude higher. The methods have been successfully utilised for the analysis of
      natural waters. Matrix effects frequently occurring in LC/MS have shown to be low
      to moderate in the case of X-ray contrast media. This work demonstrates that for
      the analysis of a large number of water contaminants, the sample pre
      concentration step could possibly be omitted.

PMID- 16810706
TI  - Improved method for isotopic and quantitative analysis of dissolved inorganic
      carbon in natural water samples.
AB  - We present here an improved and reliable method for measuring the concentration
      of dissolved inorganic carbon (DIC) and its isotope composition (delta(13)C(DIC))
      in natural water samples. Our apparatus, a gas chromatograph coupled to an
      isotope ratio mass spectrometer (GCIRMS), runs in a quasi-automated mode and is
      able to analyze about 50 water samples per day. The whole procedure (sample
      preparation, CO(2(g))-CO(2(aq)) equilibration time and GCIRMS analysis) requires
      2 days. It consists of injecting an aliquot of water into a H(3)PO(4)-loaded and
      He-flushed 12 mL glass tube. The H(3)PO(4) reacts with the water and converts the
      DIC into aqueous and gaseous CO(2). After a CO(2(g))-CO(2(aq)) equilibration time
      of between 15 and 24 h, a portion of the headspace gas (mainly CO(2)+He) is
      introduced into the GCIRMS, to measure the carbon isotope ratio of the released
      CO(2(g)), from which the delta(13)C(DIC) is determined via a calibration
      procedure. For standard solutions with DIC concentrations ranging from 1 to 25
      mmol . L(-1) and solution volume of 1 mL (high DIC concentration samples) or 5 mL
      (low DIC concentration samples), delta(13)C(DIC) values are determined with a
      precision (1sigma) better than 0.1 per thousand. Compared with previously
      published headspace equilibration methods, the major improvement presented here
      is the development of a calibration procedure which takes the carbon isotope
      fractionation associated with the CO(2(g))-CO(2(aq)) partition into account: the
      set of standard solutions and samples has to be prepared and analyzed with the
      same 'gas/liquid' and 'H(3)PO(4)/water' volume ratios. A set of natural water
      samples (lake, river and hydrothermal springs) was analyzed to demonstrate the
      utility of this new method.

PMID- 16810707
TI  - Gas chromatography/flame ionisation detection mass spectrometry for the detection
      of endogenous urine metabolites for metabonomic studies and its use as a
      complementary tool to nuclear magnetic resonance spectroscopy.
AB  - Metabonomics is a relatively new field of research in which the total pool of
      metabolites in body fluids or tissues from different patient groups is subjected
      to comparative analysis. Nuclear magnetic resonance (NMR) spectroscopy is the
      technology that is currently most widely used for the analysis of these highly
      complex metabolite mixtures, and hundreds of metabolites can be detected without
      any upfront separation. We have investigated in this study whether gas
      chromatography (GC) separation in combination with flame ionisation detection
      (FID) and mass spectrometry (MS) detection can be used for metabolite profiling
      from urine. We show that although GC sample preparation is much more involved
      than for NMR, hundreds of metabolites can reproducibly be detected and analysed
      by GC. We show that the data quality is sufficiently high--particularly if
      appropriate baseline correction and time-warping methods are applied--to allow
      for data comparison by chemometrics methods. A sample set of urines from eleven
      healthy human volunteers was analysed independently by GC and NMR, and subsequent
      chemometrics analysis of the two datasets showed some similar features. As judged
      by NIST database searches of the GC/MS data some of the major metabolites that
      are detected by NMR are also visible by GC/MS. Since in contrast to NMR every
      peak in GC corresponds to a single metabolite, the electron ionisation spectra
      can be used to quickly identify metabolites of interest if their reference
      spectra are present in a searchable database. In summary, we show that GC is a
      method that can be used as a complementary tool to NMR for metabolite profiling
      of urine samples.

PMID- 16810708
TI  - Designer drug 2,4,5-trimethoxyamphetamine (TMA-2): studies on its metabolism and
      toxicological detection in rat urine using gas chromatographic/mass spectrometric
      techniques.
AB  - Studies are described on the metabolism and the toxicological detection of the
      amphetamine-derived designer drug 2,4,5-trimethoxyamphetamine (TMA-2) in rat
      urine using gas chromatographic/mass spectrometric (GC/MS) techniques. The
      identified metabolites indicated that TMA-2 was metabolized by oxidative
      deamination to the corresponding ketone followed by reduction to the
      corresponding alcohol, O-demethylation followed by oxidative deamination, and
      finally O,O-bis-demethylation. All metabolites carrying hydroxy groups were found
      to be partly excreted in urine as glucuronides and/or sulfates. The authors'
      systematic toxicological analysis (STA) procedure using full-scan GC/MS after
      acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation
      allowed the detection, in rat urine, of an intake of TMA-2 that corresponds to a
      common drug users' dose. Assuming similar metabolism, the described STA procedure
      in human urine should be suitable as proof of an intake of TMA-2.

PMID- 16810709
TI  - Repeated measurement of pregnancy-associated plasma protein-A (PAPP-A) in Down
      syndrome screening: a validation study.
AB  - OBJECTIVES: To confirm that measuring pregnancy-associated plasma protein-A (PAPP
      A) in both first- and second-trimester serum samples improves Down syndrome
      screening. METHODS: We selected paired first- and second-trimester stored serum
      samples from 34 Down syndrome pregnancies (cases) and 514 unaffected pregnancies
      (controls) and tested the second-trimester samples for PAPP-A and dimeric inhibin
      A (DIA). First-trimester PAPP-A measurements were already available, as were
      second-trimester measurements of alpha-fetoprotein, unconjugated estriol (uE3),
      and human chorionic gonadotrophin (hCG). RESULTS: PAPP-A was lower among cases
      than controls (0.47 MoM) in the first trimester (at an average of 12.5 weeks); in
      the second trimester, it was not different (0.91 MoM). Using repeated measures of
      PAPP-A alone, 21 of 34 cases were detected (62%, 95%CI 44% to 78%) with 5% false
      positives. At an observed 2% false-positive rate, the detection rates (DR) for
      the quadruple (69%) and serum integrated (69%) tests were lower than for the
      repeated measures test (75%). Modelled performance at 12 weeks was similar to
      these observed findings (70, 75, and 82%, respectively). If the first-trimester
      samples were collected at 10 weeks, however, DR would be higher (70, 81, and 91%,
      respectively). CONCLUSIONS: Adding a repeated measure of PAPP-A to existing serum
      markers improves Down syndrome screening to levels that are currently obtainable
      only by including ultrasound measurement of nuchal translucency (NT). Serum-based
      screening has the advantages of higher availability and reliability at a lower
      cost, resulting in a more effective screening strategy. A serum-based repeated
      measures test has a place in routine Down syndrome screening.

PMID- 16810711
TI  - Reasonable risks in clinical research: a critique and a proposal for the
      Integrative Approach.
AB  - Before participants can be enrolled in a clinical trial, an institutional review
      board (IRB) must determine that the risks that the research poses to participants
      are 'reasonable.' This paper examines the two dominant frameworks for assessing
      research risks and argues that each approach suffers from significant
      shortcomings. It then considers what issues must be addressed in order to
      construct a framework for risk assessment that (a) is grounded in a compelling
      normative foundation and (b) might provide more operationally precise guidance to
      the deliberations of various stakeholders. The paper concludes by sketching the
      outlines of what is referred to as the 'Integrative Approach' to risk assessment
      and by highlighting some of the ways in which this approach may be more promising
      than current alternatives.

PMID- 16810710
TI  - Amniotic trisomy 11 mosaicism--is it a benign finding?
AB  - OBJECTIVES: A case of prenatally diagnosed trisomy 11 mosaicism with a normal
      outcome is reported and the medical literature on prenatal detection of this
      finding is reviewed. METHODS: Proportion of cells with trisomy 11 was evaluated
      in amniocytes, fetal blood lymphocytes, newborn fibroblasts and urinary
      epithelial cells. Karyotype studies and fluorescence in situ hybridization
      analysis using the 11q13LS1 CCND1 probe were performed. RESULTS: Trisomy 11 level
      III mosaicism of 26% was detected in amniotic fluid cells. Periumbilical blood
      sampling showed a normal fetal karyotype. No fetal structural abnormalities were
      noted on ultrasound scan. The infant was spontaneously delivered and had normal
      physical findings at birth. No evidence of trisomic cells was found on extensive
      postnatal evaluation, implying an extraembryonic origin. Molecular analysis
      excluded uniparental disomy of chromosome 11. At 1 year of age, the baby is
      developing normally. CONCLUSIONS: Only three reports on trisomy 11 mosaicism
      identified at amniocentesis have been published previously, all with a normal
      outcome. Additional cases of prenatally diagnosed mosaicism for trisomy 11 are
      necessary to assess more accurately the clinical significance of this finding.

PMID- 16810712
TI  - A multivariate test for population bioequivalence.
AB  - In this article, we propose a multivariate generalization of the criteria for
      testing univariate population bioequivalence. Recently, a number of approaches
      for testing multivariate equivalence have appeared in the literature. Most of
      them consider a multivariate equivalence region, which implies simultaneous
      comparison of means in each dimension. In contrast, our proposal combines a
      comparison of means and a comparison of variances into a single aggregate
      criterion, using the trace of the covariance matrix as a scalar measure of the
      total variability. We use a confidence interval approach to multivariate
      population bioequivalence testing, similar to the univariate case. Two versions
      of the modified large-sample confidence interval for the linearized multivariate
      criterion are constructed. In a simulation study, we evaluate the empirical
      coverage of these confidence intervals and rejection rates of the corresponding
      tests in finite samples. The proposed methodology is illustrated with an example
      of testing equivalence of the spray pattern of nasal sprays.

PMID- 16810713
TI  - Robustness of a multivariate normal approximation for imputation of incomplete
      binary data.
AB  - Multiple imputation has become easier to perform with the advent of several
      software packages that provide imputations under a multivariate normal model, but
      imputation of missing binary data remains an important practical problem. Here,
      we explore three alternative methods for converting a multivariate normal imputed
      value into a binary imputed value: (1) simple rounding of the imputed value to
      the nearer of 0 or 1, (2) a Bernoulli draw based on a 'coin flip' where an
      imputed value between 0 and 1 is treated as the probability of drawing a 1, and
      (3) an adaptive rounding scheme where the cut-off value for determining whether
      to round to 0 or 1 is based on a normal approximation to the binomial
      distribution, making use of the marginal proportions of 0's and 1's on the
      variable. We perform simulation studies on a data set of 206,802 respondents to
      the California Healthy Kids Survey, where the fully observed data on 198,262
      individuals defines the population, from which we repeatedly draw samples with
      missing data, impute, calculate statistics and confidence intervals, and compare
      bias and coverage against the true values. Frequently, we found satisfactory bias
      and coverage properties, suggesting that approaches such as these that are based
      on statistical approximations are preferable in applied research to either
      avoiding settings where missing data occur or relying on complete-case analyses.
      Considering both the occurrence and extent of deficits in coverage, we found that
      adaptive rounding provided the best performance.

PMID- 16810714
TI  - Impact of modelling intra-subject variability on tests based on non-linear mixed
      effects models in cross-over pharmacokinetic trials with application to the
      interaction of tenofovir on atazanavir in HIV patients.
AB  - We evaluated the impact of modelling intra-subject variability on the likelihood
      ratio test (LRT) and the Wald test based on non-linear mixed effects models in
      pharmacokinetic interaction and bioequivalence cross-over trials. These tests
      were previously found to achieve a good power but an inflated type I error when
      intra-subject variability was not taken into account. Trials were simulated under
      H0 and several H1 and analysed with the NLME function. Different configurations
      of the number of subjects n and of the number of samples per subject J were
      evaluated for pharmacokinetic interaction and bioequivalence trials. Assuming
      intra-subject variability in the model dramatically improved the type I error of
      both interaction tests. For the Wald test, the type I error decreased from 22, 14
      and 7.7 per cent for the original (n = 12, J = 10), intermediate (n = 24, J = 5)
      and sparse (n = 40, J = 3) designs, respectively, down to 7.5, 6.4 and 3.5 per
      cent when intra-subject variability was modelled. The LRT achieved very similar
      results. This improvement seemed mostly due to a better estimation of the
      standard error of the treatment effect. For J = 10, the type I error was found to
      be closer to 5 per cent when n increased when modelling intra-subject
      variability. Power was satisfactory for both tests. For bioequivalence trials,
      the type I error of the Wald test was 6.4, 5.7 and 4.2 per cent for the original,
      intermediate and sparse designs, respectively, when modelling intra-subject
      variability. We applied the Wald test to the pharmacokinetic interaction of
      tenofovir on atazanavir, a novel protease inhibitor. A significant decrease of
      the area under the curve of atazanavir was found when patients received
      tenofovir.

PMID- 16810716
TI  - Improving point predictions of random effects for subjects at high risk.
AB  - The prediction of random effects corresponding to subject-specific
      characteristics (e.g. means or rates of change) can be very useful in medical and
      epidemiologic research. At times, one may be most interested in obtaining
      accurate and/or precise predictions for subjects whose characteristic places them
      in a tail of the distribution. While the typical posterior mean predictor
      dominates others in terms of overall mean squared error of prediction (MSEP), its
      tendency to 'overshrink' has motivated research into alternatives emphasizing
      other criteria. Here, we specifically target MSEP within a certain region (e.g.
      above a known cut-off for high risk or a specified percentile of the random
      effect distribution), and we consider minimizing this quantity with and without
      constraints on overall MSEP efficiency. We use the normal-theory random intercept
      model to derive prediction methods with potential to yield markedly better
      performance for subjects in the specified region, given a well-controlled and (if
      desired) modest concession of overall MSEP. Criteria geared toward classification
      as well as overall and regional prediction unbiasedness are also provided. We
      evaluate the proposed techniques and illustrate them using repeated measures data
      on fasting blood glucose from type 2 diabetes patients. A simulation study
      verifies that theoretical properties and relative performances of the proposed
      predictors are essentially maintained when calculating them in practice based on
      estimated mixed linear model parameters. Straightforward extensions to
      incorporate covariates and additional random effects are briefly outlined.

PMID- 16810717
TI  - Myostatin short interfering hairpin RNA gene transfer increases skeletal muscle
      mass.
AB  - BACKGROUND: Myostatin negatively regulates skeletal muscle growth. Myostatin
      knockout mice exhibit muscle hypertrophy and decreased interstitial fibrosis. We
      investigated whether a plasmid expressing a short hairpin interfering RNA (shRNA)
      against myostatin and transduced using electroporation would increase local
      skeletal muscle mass. METHODS: Short interfering RNAs (siRNAs) targeting
      myostatin were co-transfected with a myostatin-expressing plasmid into HEK293
      cells and identified for myostatin silencing by Western blot. Corresponding
      shRNAs were cloned into plasmid shRNA expression vectors. Myostatin or a randomer
      negative control shRNA plasmid was injected and electroporated into the tibialis
      anterior or its contralateral muscle, respectively, of nine rats that were
      sacrificed after 2 weeks. Six other rats received a beta-galactosidase reporter
      plasmid and were sacrificed at 1, 2, and 4 weeks. Uptake of plasmid was examined
      by beta-galactosidase expression, whereas myostatin expression was determined by
      real-time polymerase chain reaction (PCR) and Western blotting. Muscle fiber size
      was determined by histochemistry. Satellite cell proliferation was determined by
      PAX7 immunohistochemistry. Myosin heavy chain type II (MHCII) expression was
      determined by Western blot. RESULTS: beta-Galactosidase reporter plasmid was
      expressed at 1 and 2 weeks but diminished by 4 weeks in tibialis anterior
      skeletal muscle. Myostatin shRNA reduced myostatin mRNA and protein expression by
      27 and 48%, respectively. Tibialis anterior weight, fiber size, and MHCII
      increased by 10, 34, and 38%, respectively. Satellite cell number was increased
      by over 2-fold. CONCLUSIONS: This is the first demonstration that myostatin shRNA
      gene transfer is a potential strategy to increase muscle mass.

PMID- 16810718
TI  - Deep brain stimulation: preoperative issues.
AB  - Numerous factors need to be taken into account in deciding whether a patient with
      Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient
      related personal factors including age and the presence of other comorbid
      disorders need to be considered. Neuropsychological and neuropsychiatric concerns
      relate both to the presurgical status of the patient and to the potential for
      surgery to result in new problems postoperatively. A number of factors related to
      the underlying PD need to be considered, including the specific parkinsonian
      motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous
      medical therapies, including benefit from current therapy and adverse effects,
      and past surgical treatments. Definable causes of Parkinsonism, particularly
      atypical Parkinsonisms, should be considered. Finally, methods of evaluating
      outcomes should be defined and formalized. This is a report from the Consensus on
      Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the
      Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The
      report has been endorsed by the Scientific Issues Committee of the MDS and the
      American Society of Stereotactic and Functional Neurosurgery. It outlines answers
      to a series of questions developed to address all aspects of deep brain
      stimulation preoperative decision-making.

PMID- 16810719
TI  - Deep brain stimulation: postoperative issues.
AB  - Numerous factors need to be taken into account when managing a patient with
      Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as
      when to begin programming, how to conduct a programming screen, how to assess the
      effects of programming, and how to titrate stimulation and medication for each of
      the targeted sites need to be addressed. Follow-up care should be determined,
      including patient adjustments of stimulation, timing of follow-up visits and
      telephone contact with the patient, and stimulation and medication conditions
      during the follow-up assessments. A management plan for problems that can arise
      after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction,
      muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and
      behavioral and cognitive problems should be developed. Long-term complications
      such as infection or erosion, loss of effect, intermittent stimulation,
      tolerance, and pain or discomfort can develop and need to be managed. Other
      factors that need consideration are social and job-related factors, development
      of dementia, general medical issues, and lifestyle changes. This report from the
      Consensus on Deep Brain Stimulation for Parkinson's Disease, a project
      commissioned by the Congress of Neurological Surgeons and the Movement Disorder
      Society, outlines answers to a series of questions developed to address all
      aspects of DBS postoperative management and decision-making with a systematic
      overview of the literature (until mid-2004) and by the expert opinion of the
      authors. The report has been endorsed by the Scientific Issues Committee of the
      Movement Disorder Society and the American Society of Stereotactic and Functional
      Neurosurgery.

PMID- 16810720
TI  - Electrophysiological mapping for the implantation of deep brain stimulators for
      Parkinson's disease and tremor.
AB  - The vast majority of centers use electrophysiological mapping techniques to
      finalize target selection during the implantation of deep brain stimulation (DBS)
      leads for the treatment of Parkinson's disease and tremor. This review discusses
      the techniques used for physiological mapping and addresses the questions of how
      various mapping strategies modify target selection and outcome following
      subthalamic nucleus (STN), globus pallidus internus (GPi), and ventralis
      intermedius (Vim) deep brain stimulation. Mapping strategies vary greatly across
      centers, but can be broadly categorized into those that use microelectrode or
      semimicroelectrode techniques to optimize position prior to implantation and
      macrostimulation through a macroelectrode or the DBS lead, and those that rely
      solely on macrostimulation and its threshold for clinical effects (benefits and
      side effects). Microelectrode criteria for implantation into the STN or GPi
      include length of the nucleus recorded, presence of movement-responsive neurons,
      and/or distance from the borders with adjacent structures. However, the threshold
      for the production of clinical benefits relative to side effects is, in most
      centers, the final, and sometimes only, determinant of DBS electrode position.
      Macrostimulation techniques for mapping, the utility of microelectrode mapping is
      reflected in its modification of electrode position in 17% to 87% of patients
      undergoing STN DBS, with average target adjustments of 1 to 4 mm. Nevertheless,
      with the absence of class I data, and in consideration of the large number of
      variables that impact clinical outcome, it is not possible to conclude that one
      technique is superior to the other in so far as motor Unified Parkinson's Disease
      Rating Scale outcome is concerned. Moreover, mapping technique is only one out of
      many variables that determine the outcome. The increase in surgical risk of
      intracranial hemorrhage correlated to the number of microelectrode trajectories
      must be considered against the risk of suboptimal benefits related to omission of
      this technique.

PMID- 16810721
TI  - Deep brain stimulation for Parkinson's disease.

PMID- 16810723
TI  - Synthesis of single-crystalline platinum nanorods within a soft crystalline
      surfactant-Pt(II) complex.
AB  - Single-crystalline platinum nanorods, monodisperse in diameter, are synthesized
      through a simple process at room temperature, in cetyltrimethyl ammonium bromide
      (CTAB) solution. The complexation of the CTA+ surfactant ion with
      tetrachloroplatinate in the presence of hexanol leads to the formation of a
      precipitate with a lamellar crystalline structure. The reduction of Pt(II) metal
      ions to Pt(0) is carried out using gamma radiolysis. Transmission electron
      microscopy (TEM) observations of the nanoparticles extracted from the solution,
      three weeks after radiolysis, revealed single-crystalline Pt nanorods,
      monodisperse in diameter (3-4 nm) and 20-60 nm long. By following the shape of
      the nanorods at various stages of the growth, it was found that the single
      crystalline nanorods grow by coalescence of spherical seeds 3-4 nm in diameter.
      This suggests an aggregative mechanism similar to that recently observed for
      silver particles in solution.

PMID- 16810725
TI  - Electrostatic-field-induced enhancement of gas mixture separation in metal
      organic frameworks: a computational study.

PMID- 16810722
TI  - Deep brain stimulation for Parkinson's disease: surgical technique and
      perioperative management.
AB  - Deep brain stimulation (DBS) is a widely accepted therapy for medically
      refractory Parkinson's disease (PD). Both globus pallidus internus (GPi) and
      subthalamic nucleus (STN) stimulation are safe and effective in improving the
      symptoms of PD and reducing dyskinesias. STN DBS is the most commonly performed
      surgery for PD as compared to GPi DBS. Ventral intermediate nucleus (Vim) DBS is
      infrequently used as an alternative for tremor predominant PD patients. Patient
      selection is critical in achieving good outcomes. Differential diagnosis should
      be emphasized as well as neurological and nonneurological comorbidities. Good
      response to a levodopa challenge is an important predictor of favorable long-term
      outcomes. The DBS surgery is typically performed in an awake patient and involves
      stereotactic frame application, CT/MRI imaging, anatomical targeting,
      physiological confirmation, and implantation of the DBS lead and pulse generator.
      Anatomical targeting consists of direct visualization of the target in MR images,
      formula-derived coordinates based on the anterior and posterior commissures, and
      reformatted anatomical stereotactic atlases. Physiological verification is
      achieved most commonly via microelectrode recording followed by implantation of
      the DBS lead and intraoperative test stimulation to assess benefits and side
      effects. The various aspects of DBS surgery will be presented.

PMID- 16810726
TI  - Hydrogen atom and hydride anion addition to adenine: structures and energetics.
AB  - The radicals and anions derived from the 9H tautomer of adenine by adding a
      hydrogen atom to one of the four double bonds of the adenine framework have been
      studied. Computations were carried out using a carefully calibrated density
      functional (B3LYP) method and basis set (DZP++). Optimized geometries, energies,
      and vibrational frequencies are predicted for eight radicals and anions. The
      radicals are found to lie in a range of 22 kcal mol(-1), with the radical derived
      by addition to the C(8) carbon atom being the lowest lying energetically. The
      anions are predicted to be bound species in the gas phase with an energetic range
      of 43 kcal mol(-1). Anions produced by addition of a hydride ion to adenine
      carbon atoms are found to be the most favorable. Six of the anions are predicted
      to be stable species with respect to electron detachment. The adiabatic electron
      affinities, vertical electron affinities, and vertical detachment energies are
      computed for the first time. Electron affinities for these radicals range from
      0.0 to 2.0 eV. Radicals produced by addition to a nitrogen atom have near-zero
      adiabatic electron affinities, while radicals produced by addition at carbon
      atoms have considerably higher electron affinities.

PMID- 16810727
TI  - Incorporation of anthracene into zeolites: confinement effect on the
      recombination rate of photoinduced radical cation-electron pair.
AB  - FT-Raman spectrometry in combination with diffuse reflectance UV/Vis absorption
      (DRUVv) and fluorescence emission indicate that complete anthracene (ANT)
      sorption as intact molecules takes place over 6 months in the medium pores of non
      Bronsted acidic M(n)ZSM-5 zeolites (n=0.0, 3.4, 6.6; M=Na+, K+, Rb+, Cs+) with 1
      ANT per unit cell loading. The combined effect of confinement and electrostatic
      field induced by bulky cations (Rb+, Cs+) leads to specific changes in the
      occluded ANT Raman spectra after very long organization periods (one year). The
      laser photolysis (266 nm, 355 nm) of ANT@M(n)ZSM-5 equilibrated samples generates
      long-lived charge separated species in aluminum rich zeolites (n=3.4, 6.6). The
      very long-lived radical pairs are characterized by conventional DRUVv and CW-EPR
      spectroscopy. The direct charge recombination rates of ANT.+-electron pairs are
      dispersive, extending over a broad range of timescales. The kinetic constant
      values are found to increase dramatically with the aluminum content and increase
      markedly with M+ according to the following order Na+ < K+ < Rb+ < Cs+. The small
      reorganization energy (lambda) of ZSM-5 zeolite pores coupled with large negative
      free energy changes (-DeltaG degrees ) between the ground state ANT oxidation
      potential and Fermi level of aluminum rich M(n)ZSM-5 explain the observed trends
      of the ANT.+@M(n)ZSM-5.- charge recombination rates.

PMID- 16810728
TI  - An alternative approach to the g-matrix: theory and applications.
AB  - Starting from the formula proposed by Gerloch and McMeeking in 1975, the
      electronic g-matrix is expressed as a sum of two matrices called Lambda and Sigma
      describing the orbital and spin contributions respectively. This approach is
      applied on benchmark diatomic and triatomic molecules, and on TiF3 and
      Cu(NH3)4(2+) using either CASPT2 or CCSD(T) methods to calculate the spin-free
      states and SO-RASSI to calculate spin-orbit coupling. Results compare very well
      to experimental data and to previous theoretical work; and, for each molecule,
      the anisotropy of the g-matrix is modeled by the mean of a few parameters.

PMID- 16810729
TI  - Determination of the hydration number of gadolinium(III) complexes by high-field
      pulsed 17O ENDOR spectroscopy.
AB  - Pulsed 17O Mims electron-nuclear double resonance (ENDOR) spectroscopy at the W
      band (95 GHz) and D band (130 GHz) is used for the direct determination of the
      water coordination number (q) of gadolinium-based magnetic resonance imaging
      (MRI) contrast agents. Spectra of metal complexes in frozen aqueous solutions at
      approximately physiological concentrations can be obtained either in the presence
      or absence of protein targets. This method is an improvement over the 1H ENDOR
      method described previously, which involved the difference ENDOR spectrum of
      exchangeable protons from spectra taken in H2O and D2O. In addition to
      exchangeable water protons, the 1H ENDOR method is also sensitive to other
      exchangeable protons, and it is shown here that this method can overestimate
      hydration numbers for complexes with exchangeable protons at GdH distances
      similar to that of the coordinated water, for example, from NH groups. The 17O
      method does not suffer from this limitation. 17O ENDOR spectroscopy is applied to
      Gd(III) complexes containing zero, one, or two inner-sphere water molecules. In
      addition, 13C and 1H ENDOR studies were performed to assess the extent of
      methanol coordination, since methanol is used to produce a glass in these
      experiments. Under the experimental conditions used for the hydration number
      determination (30 mol % methanol), fewer than 15 % of the coordination sites were
      found to be occupied by methanol.

PMID- 16810731
TI  - Bioinformatics of protein allergenicity.

PMID- 16810732
TI  - Food allergy.
AB  - This article reviews the classification of food allergies, their prevalence,
      pathophysiology, diagnosis, treatment and prognosis.

PMID- 16810733
TI  - Introduction to bioinformatics.
AB  - This article introduces the field of bioinformatics and describes bioinformatic
      approaches and their application to the study of protein allergens. The
      predominant bioinformatics tools and resources are listed and discussed.

PMID- 16810734
TI  - Practical and predictive bioinformatics methods for the identification of
      potentially cross-reactive protein matches.
AB  - A bioinformatics comparison of proteins introduced into food crops through
      genetic engineering provides a mechanism to identify those proteins that may
      present an increased risk of allergic reactions for individuals with existing
      allergies. The goal is to identify proteins that are known to be allergens or are
      so similar to an allergen that they may induce allergic cross-reactions. Three
      comparative approaches have traditionally been used, or considered for safety
      evaluations. One identifies any short (6-8) amino acid segment of the protein
      that exactly matches a known allergen sequence. The second is an overall primary
      sequence comparison using Basic Local Alignment Search Tool (BLAST) or FASTA to
      find matches of greater than 35% identity over 80 amino acids. The third is based
      on 3-D prediction programs to identify 3-D similarities that might predict
      potential cross-reactivity. The utility of each of these approaches was debated
      in the bioinformatics workshop. The consensus agreement from the expert workshop
      participants was that the short-segment match (e. g., 6-8 amino acids) provides
      an unacceptably high rate of false positive matches and an uncertain rate of true
      positive matches, and was not particularly useful for an allergenicity evaluation
      performed in the context of comprehensive safety evaluation. There was no
      consensus regarding the most appropriate bioinformatics method, an acceptable
      scoring criteria for triggering closer examination subsequent to a positive
      match, or an acceptable scoring mechanism for ranking the utility of the various
      3-D approaches that were discussed during the workshop. However, the general
      consensus was that the most practical approach at this time is to evaluate
      primary sequence identities to known allergens using either FASTA or BLAST. While
      there was good agreement that identities of greater than 35% over 80 or more
      amino acids (recommended by Codex in 2003) is quite conservative, the conclusion
      was that additional data or studies would be needed to justify changing this
      criterion as there is some evidence that some individuals sensitized to proteins
      in evolutionarily conserved protein families may experience cross-reactions to
      proteins sharing approximately 40% identity.

PMID- 16810738
TI  - Dissecting CXCR5+ T cell populations--on the quest for a better understanding of
      B cell help during T dependent antibody responses.
AB  - High affinity antibody responses against protein antigens critically depend on T
      cell help during the germinal center reaction. So called follicular helper T
      cells (T(FH)), present in the germinal centers of human tonsils, have been
      characterised by the expression of CXCR5; however, only subgroups of the
      heterogeneous CXCR5 T cell population strongly support antibody production. A
      paper in this issue of the European Journal of Immunology demonstrates that high
      expression of the inducible co-stimulator (ICOS) molecule, rather than CD57,
      correlates with the follicular helper function. This result represents another
      step towards a better understanding of the complexity of the different T cell
      subpopulations participating in the germinal center reaction.

PMID- 16810739
TI  - IL-4 induces expression of TARC/CCL17 via two STAT6 binding sites.
AB  - A cardinal feature of allergic disorders and immune responses is enhanced
      leukocyte trafficking. This is largely orchestrated by chemokines. The CC
      chemokine thymus- and activation-regulated chemokine (TARC/CCL17) selectively
      attracts Th2 cells via the G protein-coupled chemokine receptor CCR4. We show
      here that TARC/CCL17 is expressed by human T cells upon stimulation with IL-4.
      Mapping of the transcriptional start site revealed the presence of two putative
      STAT6 binding motifs in proximity to the start position. EMSA and chromatin
      immunoprecipitation experiments demonstrated that STAT6 was able to bind to both
      motifs. A fragment of the TARC/CCL17 promoter containing both sites was tested in
      reporter gene assays for IL-4 inducibility. The promoter was inducible in a STAT6
      deficient cell line only after introduction of functional STAT6. When mutations
      were inserted into one of the STAT6 motifs, IL-4-induced promoter activation was
      reduced. With both sites mutated, inducibility was completely abrogated. These
      data demonstrate collectively that T cells serve as a source of TARC/CCL17 when
      stimulated with IL-4 and that STAT6 is essential for this.

PMID- 16810741
TI  - Study of Sonic hedgehog signaling pathway related molecules in gastric carcinoma.
AB  - AIM: To study the expression of Sonic hedgehog pathway-related molecules, Sonic
      hedgehog (Shh) and Gli1 in gastric carcinoma. METHODS: Expression of Shh in 56
      gastric specimens including non-cancerous gastric tissues, gastric
      adenocarcinoma, gastric squamous cell carcinoma was detected by RT-PCR, in situ
      hybridization and immunohistochemistry. Expression of Gli1 was observed by in
      situ hybridization. RESULTS: The positive rate of Shh and Gli1 expression was
      0.0%, 0.0% in non-cancerous gastric tissues while it was 66.7%, 57.8%
      respectively in gastric adenocarcinoma, and 100%, 100% respectively in gastric
      squamous cell carcinoma. There was a significant difference between the non
      cancerous gastric tissues and gastric carcinoma (P<0.05). Elevated expression of
      Shh and Gli1 in gastric tubular adenocarcinoma was associated with poorly
      differentiated tumors while the expression was absent in gastric mucinous
      adenocarcinoma. CONCLUSION: The elevated expression of Shh and Gli1 in gastric
      adenocarcinoma and gastric squamous cell carcinoma shows the involvement of
      activated Shh signaling in the cellular proliferation of gastric carcinogenesis.
      It suggests Shh signaling gene may be a new and good target gene for gastric
      tumor diagnosis and therapy.

PMID- 16810742
TI  - Correlative studies on uPA mRNA and uPAR mRNA expression with vascular
      endothelial growth factor, microvessel density, progression and survival time of
      patients with gastric cancer.
AB  - AIM: To investigate the correlations between the expression of urokinase-type
      plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and vascular
      endothelial growth factor (VEGF) protein and clinicopathologic features,
      microvessel density (MVD) and survival time. METHODS: In situ hybridization and
      immuno-histochemistry techniques were used to study the expressions of uPA mRNA,
      uPAR mRNA, VEGF and CD34 protein in 105 gastric carcinoma specimens. RESULTS:
      Expressions of uPA mRNA, uPAR mRNA and VEGF protein were observed in 61 (58.1%)
      cases, 70 (66.7%) cases and 67 (63.8%) cases, respectively. The uPA mRNA and uPAR
      mRNA positive expression rates in infiltrating-type cases (73.7%, 75.4%), stage
      III-IV (72.1%, 75.4%), vessel invasion (63.2%, 69.9%), lymphatic metastasis
      (67.1%, 74.4%) and distant metastasis (88.1%, 85.7%) were significantly higher
      than those of the expanding-type (chi2 = 15.57, P = 0.001; chi2 = 6.91, P =
      0.046), stage I-II (chi2 = 19.22, P = 0.001; chi2 = 16.75, P = 0.001), non-vessel
      invasion (chi2 = 11.92, P = 0.006; chi2 = 14.15, P = 0.002), non-lymphatic
      metastasis (chi2 = 28.41, P = 0.001; chi2 = 22.5, P = 0.005) and non-distant
      metastasis (chi2 = 12.32, P = 0.004; chi2 = 17.42, P = 0.002; chi2 = 11.25, P =
      0.012; chi2 = 18.12, P = 0.002). The VEGF positive expression rates in
      infiltrating-type cases (75.4%), stage III-IV (88.5%), vessel invasion (82.9%),
      lymphatic metastasis (84.3%) and distant metastasis (95.2%) were significantly
      higher than those of the expanding-type (chi2 = 9.61, P = 0.021), stage I-II
      (chi2 = 16.66, P = 0.001), non-vessel invasion (chi2 = 29.38, P = 0.001), non
      lymphatic metastasis (chi2 = 18.68, P = 0.005), and non-distant metastasis (chi2
      = 22.72, P = 0.007; chi2 = 21.62, P = 0.004). The mean MVD in the specimens
      positive for the uPA mRNA, uPAR mRNA and VEGF protein was markedly higher than
      those with negative expression groups. Moreover, a positive relation between MVD
      and uPA mRNA (rs = 0.199, P = 0.042), uPAR mRNA (rs = 0.278, P = 0.035), and VEGF
      (rs = 0.398, P = 0.048) expressions was observed. The mean survival time in cases
      with positive uPA mRNA, uPAR mRNA and VEGF protein expression or MVD value > or =
      54.9 was significantly shorter than those in cases with negative expression or
      MVD value < 54.9. CONCLUSION: uPA and uPAR expressions are correlated with
      enhanced VEGF-induced tumor angiogenesis and may play a role in invasion and
      nodal metastasis of gastric carcinoma, thereby serving as prognostic markers of
      gastric cancer.

PMID- 16810740
TI  - Current issues in endoscope reprocessing and infection control during
      gastrointestinal endoscopy.
AB  - The purpose of this article is to review the evidence regarding transmission of
      infection during gastrointestinal endoscopy, factors important in endoscope
      reprocessing and infection control, areas to focus on to improve compliance, and
      recent developments and advances in the field.

PMID- 16810743
TI  - Effect of blocking IGF-I receptor on growth of human hepatocellular carcinoma
      cells.
AB  - AIM: To study the expression level and localization of insulin-like growth factor
      -I receptor (IGF-IR) in HepG2 cells and Chang liver cells, and to observe the
      effect of anti-IGF-IR monoclonal antibody (alphaIR3) on the growth of HepG2
      cells. METHODS: The expression of IGF-IR in HepG2 cells and Chang liver cells was
      detected by immunohistochemistry. The influences of alphaIR3 on proliferation and
      apoptosis were examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and electron microscopy, respectively.
      Flow cytometry (FCM) was applied for the analysis of cell cycle and apoptosis was
      observed under electron microscope. RESULTS: IGF-IR was located in the membranes
      of both HepG2 and Chang liver cell lines, and the expression level of IGF-IR was
      higher in HepG2 cells than in Chang liver cells. Treated with 0.1 microg/mL
      alphaIR3 for 48 h in vitro, the cell growth index (GI) of HepG2 cells was
      significantly higher than that of control (103.41% vs 100%, P<0.01). However, the
      alphaIR3 for 24 h at final concentration of 4.0 microg/mL made the GI of HepG2
      cells lower than that of control (93.37% vs 100%, P<0.01). Compared with control,
      treated with alphaIR3 for 48 h at final concentrations ranging from 1.0 microg/mL
      to 4.0 microg/mL markedly reduced the GIs of HepG2 cells (97.63%, 97.16%, 95.13%,
      92.53% vs 100%, P<0.05 or P<0.01), treated with alphaIR3 for 72 h at final
      concentrations ranging from 0.2 microg/mL to 4.0 microg/mL decreased the GIs of
      HepG2 cells obviously (95%, 91.63%, 90.77%, 89.84%, 88.51% vs 100%, P<0.01), and
      treated with alphaIR3 for 96 h at final concentrations ranging from 0.5 microg/mL
      to 4.0 microg/mL made GIs of HepG2 cells lower significantly (88.86%, 83.97%,
      79.81%, 77.24%, 70.51% vs 100%, P<0.05 or P<0.01). Moreover, treated with
      alphaIR3 from 24 h to 96 h at final concentrations ranging from 0.2 microg/mL to
      4.0 microg/mL reduced the GI of HepG2 cells from 97.63% to 70.51% in a dose- and
      time-dependent manner. Also, alphaIR3 treatment for 72 h at final concentration
      from 0.5 microg/mL to 2.0 microg/mL increased the proportion of G0/G1 phase cells
      (61.73%, 67.1%, 83.7%, 76.87% vs 44.47%, P<0.01) and significantly decreased that
      of S phase cells (28.63%, 25.13%, 15.63%, 23.13% vs 53.17%, P<0.01), in contrast
      to the proportion of G2/M phase cells. The apoptotic rates of HepG2 cells were
      increased more than that of control (7.83%, 16.13%, 21.1%, 37.73% vs 4.13%,
      P<0.01). CONCLUSION: The malignant cell phenotype of human hepatocarcinoma cell
      is related to overexpression of IGF-IR. The blockage of IGF-IR with alphaIR3 may
      contribute to the inhibition of proliferation and induction of apoptosis in HepG2
      cells.

PMID- 16810744
TI  - Effects of adenoviral-mediated gene transduction of NK4 on proliferation,
      movement, and invasion of human colonic LS174T cancer cells in vitro.
AB  - AIM: To investigate the inhibitory effects of a recombinant adenovirus vector
      that expresses NK4, a truncated form of human hepatocyte growth factor (HGF), on
      human colonic adenocarcinoma cells in vitro to establish a basis for future NK4
      gene cancer therapy. METHODS: Cells from the LS174T human colonic adenocarcinoma
      cell line were infected with recombinant adenovirus rvAdCMV/NK4 and the effects
      of the manipulation on tumor cell proliferation, scatter, migration, and basement
      membrane invasion were assessed. Cells infected with a recombinant adenovirus
      vector (Ad-LacZ) expressing beta-galactosidase served as the controls. RESULTS:
      We found that rvAdCMV/NK4 expression attenuated HGF-induced tumor cell scatter,
      migration, and basement membrane invasion (P<0.05), but did not inhibit tumor
      cell proliferation. CONCLUSION: HGF-induced LS174T tumor cell scatter, migration,
      and invasion can be antagonized by the recombinant NK4-expressing adenovirus.

PMID- 16810745
TI  - Characterization of flgK gene and FlgK protein required for H. pylori
      colonization--from cloning to clinical relevance.
AB  - AIM: To characterize the role of flgK and its protein product in H. pylori
      colonization. METHODS: The PCR cloning method identified the flgK gene. An
      isogenic flgK mutant was constructed by gene replacement and confirmed by
      Southern blot analysis and PCR analysis. The recombinant FlgK protein (r-FlgK)
      was purified. Electron microscopy (EM) was applied to demonstrate the flagella of
      H. pylori. An in vitro motility test was assessed in semisolid medium. The
      densities of H. pylori colonization with either the wild-type strain or its flgK
      mutant were compared among BALB/c mice with or without pre-immunization with r
      FlgK. The serological responses to r-FlgK were analyzed for 70 clinical patients
      with different densities of H. pylori colonization. RESULTS: From a duodenal
      ulcer strain, the flgK gene was cloned and it contained 1821 bp, with a 95.7%
      identity to the published sequences. No flagella were observed under EM for the
      mutant strain, which had a loss of motility. H. pylori density was lower in the
      BALB/c mice inoculated by the mutant or with pre-immunization with r-FlgK
      compared to unimmunized mice or mice inoculated by the wild-type strain (P<0.05).
      In the H. pylori-infected patients, the serological responses to r-FlgK were
      uniformly low in titer. CONCLUSION: FlgK encoded by flgK is important for
      flagella formation and H. pylori motility. Deficiency in FlgK or an enhanced
      serological response to r-FlgK can interfere with H. pylori colonization. FlgK of
      H. pylori could be a novel target for vaccination.

PMID- 16810746
TI  - Experimental gastric dysrhythmias and its correlation with in vivo gastric muscle
      contractions.
AB  - AIM: To study the direct correlation between gastric dysrhythmias and in vivo
      gastric muscle tone. METHODS: Five healthy dogs were implanted with 4 pairs of
      electrodes along the greater curvature, with a strain gauge (SG) being sutured
      parallel to the distal electrodes (2 cm above the pylorus). Intravenous
      vasopressin was given to induce gastric dysrhythmia. The percentage of regular
      slow waves and SG energy were calculated. RESULTS: (1) the regularity of gastric
      myoelectric activity (GMA) was reduced during and after infusion of vasopressin;
      (2) SG energy was significantly decreased during the infusion of vasopressin; (3)
      the decrease in SG energy was well correlated with the reduction in GMA
      regularity; (4) SG energy was negatively correlated with bradygastria and
      tachygastria. CONCLUSION: Vasopressin inhibits gastric contractions and impairs
      gastric slow waves; gastric dysrhythmias are associated with the reduced antral
      muscle contractions, and are indicative of antral hypomotility.

PMID- 16810747
TI  - Caerulin-induced pancreatitis in rats: histological and genetic expression
      changes from acute phase to recuperation.
AB  - AIM: To study the histological and pancreatitis-associated protein mRNA
      accumulation changes of pancreas from acute phase of caerulin-induced
      pancreatitis to recuperation in rats. METHODS: Acute pancreatitis was induced by
      caerulein in male Wistar rats and followed up for 90 d by histological and mRNA
      analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30,
      60, 90 d post-induction. Edema (E), polymorphonuclear neutrophil (PMN)
      infiltration, cytoplasmic vacuolization (V), zymogen granule depletion (ZD) and
      acinar disorganization (AD) were microscopically evaluated. Accumulation of
      pancreatitis-associated protein (PAP) and L13A mRNAs were quantified by real-time
      PCR. RESULTS: The main histological changes appeared at 9 h post-induction for
      PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD,
      respectively. All the parameters were recovered after 5 d, except for ZD which
      delayed more than 30 d. The main AD was observed after 15 d and values returned
      to normal after 30 d. Similarly to histological changes, accumulation of the PAP
      mRNA was increased at 9 h with the highest accumulation at 24 h and differences
      disappeared after 5 d. CONCLUSION: From the acute phase to recuperation of
      pancreatitis, regeneration and re-differentiation of pancreas occur and PAP
      expression is exclusively an acute response of pancreatitis.

PMID- 16810749
TI  - Depression of biofilm formation and antibiotic resistance by sarA disruption in
      Staphylococcus epidermidis.
AB  - AIM: To study the effects of disruption of sarA gene on biofilm formation and
      antibiotic resistance of Staphylococcus epidermidis (S. epidermidis). METHODS: In
      order to disrupt sarA gene, the double-crossover homologous recombination was
      applied in S. epidermidis RP62A, and tetracycline resistance gene (tet) was used
      as the selective marker which was amplified by PCR from the pBR322 and inserted
      into the locus between sarA upstream and downstream, resulting in pBT2delta sarA.
      By electroporation, the plasmid pBT2delta sarA was transformed into S.
      epidermidis. Gene transcription was detected by real-time reverse transcription
      PCR (RT-PCR). Determination of biofilm was performed in 96-well flat-bottomed
      culture plates, and antibiotic resistance was analyzed with test tube culture by
      spectrophotometry at 570 nm respectively. RESULTS: A sarA disrupted strain named
      S. epidermidis RP62Adelta sarA was constructed, which was completely defective in
      biofilm formation, while the sarA complement strain RP62Adelta sarA (pHPS9sarA)
      restored the biofilm formation phenotype. Additionally, the knockout of sarA
      resulted in decreased erythromycin and kanamycin resistance of S. epidermidis
      RP62A. Compared to the original strain, S. epidermidis RP62Adelta sarA had an
      increase of the sensitivity to erythromycin at 200-400 microg/mL and kanamycin at
      200-800 microg/mL respectively. CONCLUSION: The knockout of sarA can result in
      the defect in biofilm formation and the decreased erythromycin and kanamycin
      resistance in S. epidermidis RP62A.

PMID- 16810748
TI  - Inhibitory effects of antisense phosphorothioate oligodeoxynucleotides on
      pancreatic cancer cell Bxpc-3 telomerase activity and cell growth in vitro.
AB  - AIM: To investigate the effect of telomerase hTERT gene antisense oligonucleotide
      (hTERT-ASO) on proliferation and telomerase activity of pancreatic cancer cell
      line Bxpc-3. METHODS: MTT assay was used to detect the effect of different doses
      of hTERT-ASO on proliferation of Bxpc-3 cell for different times. To study the
      anti-tumor activity, the cells were divided into three groups: Control group
      (pancreatic cancer cell Bxpc-3); antisense oligonucleotide (hTERT-ASO) group; and
      nosense oligonucleotide group decorated with phosphorothioate. Telomerase
      activity was detected using TRAP-PCR-ELISA. Cell DNA distribution was examined
      using flow cytometry assay. Cell apoptosis was observed by transmission electron
      microscope in each group. RESULTS: After treatment with 6 mmol/L hTERT-ASO, cell
      proliferation was inhibited in dose- and time-dependent manner. The telomerase
      activity decreased after treatment with hTERT-ASO for 72 h. Flow cytometry showed
      the cell number of G0/G1 phase increased from 2.7% to 14.7%, the cell number of S
      phase decreased from 72.7% to 51.0%, and a sub-G1 stage cell apoptosis peak
      appeared in front of G1 stage. CONCLUSION: Telomerase antisense oligodeoxy
      nucleotide can inhibit the proliferation of pancreatic cancer cell line Bxpc-3
      and decrease the telomerase activity and increase cell apoptosis rate in vitro.

PMID- 16810750
TI  - Differentiation of human umbilical cord blood stem cells into hepatocytes in vivo
      and in vitro.
AB  - AIM: To study the condition and potentiality of human umbilical cord blood stem
      cells (HUCBSC) to differentiate into hepatocytes in vivo or in vitro. METHODS: In
      a cell culture study of human umbilical cord blood stem cell (HUCBSC)
      differentiation, human umbilical cord blood mononuclear cells (HUCBMNC) were
      separated by density gradient centrifugation. Fibroblast growth factor (FGF) and
      hepatocyte growth factor (HGF) and the supernatant of fetal liver were added in
      the inducing groups. Only FGF was added in the control group. The expansion and
      differentiation of HUCBMNC in each group were observed. Human alpha fetoprotein
      (AFP) and albumin (ALB) were detected by immunohistochemistry. In the animal
      experiments, the survival SD rats with acute hepatic injury after carbon
      tetrachloride (CCL4) injection 48 h were randomly divided into three groups. The
      rats in group A were treated with human umbilical cord blood serum. The rats in
      group B were treated with HUCBMNC transplantation. The rats in group C were
      treated with HUCBMNC transplantation followed by intraperitoneal cyclophosphamide
      for 7 d. The rats were killed at different time points after the treatment and
      the liver tissue was histopathologically studied and human AFP and ALB detected
      by immunohistochemistry. The human X inactive-specific transcript gene fragment
      in the liver tissue was amplified by PCR to find human DNA. RESULTS: The results
      of cell culture showed that adherent cells were stained negative for AFP or ALB
      in control group. However, the adherent cells in the inducing groups stained
      positive for AFP or ALB. The result of animal experiment showed that no human AFP
      or ALB positive cells present in the liver tissue of group A (control group).
      However, many human AFP or ALB positive cells were scattered around sinus
      hepaticus and the central veins of hepatic lobules and in the portal area in
      group B and group C after one month. The fragment of human X chromagene could be
      detected in the liver tissue of groups B and C, but not in group A. CONCLUSION:
      Under certain conditions HUCBSC can differentiate into liver cells in vivo and in
      vitro.

PMID- 16810751
TI  - Predicting utility of a model for end stage liver disease in alcoholic liver
      disease.
AB  - AIM: To validate the statistic utility of both the Maddrey Discriminant Function
      score and the Model for End-Stage Liver Disease as predictors of short term (30 d
      and 90 d) mortality in patients with alcoholic hepatitis and to assess prognostic
      factors among clinical characteristics and laboratory variables of patients with
      alcoholic hepatitis. METHODS: Thirty-four patients with the diagnosis of
      alcoholic hepatitis admitted to Hippokration University Hospital of Athens from
      2000 to 2005 were assessed in the current retrospective study and a statistical
      analysis was conducted. RESULTS: 30- and 90-d mortality rates were reported at
      5.9% (2/34) and 14.7% (5/34), respectively. Significant correlation was
      demonstrated for the Model for End-Stage Liver Disease (P30 = 0.094, P90 = 0.046)
      and the Maddrey Discriminant Function score (P30 = 0.033, P90 = 0.038) with 30-
      and 90-d mortality whereas a significant association was also established for
      alanine aminotransferase (P = 0.057), fibrin degradation products (P = 0.048) and
      C-reactive protein (P = 0.067) with 90-d mortality. For 30-d mortality the Area
      Under the Curve was 0.969 (95%CI: 0.902-1.036, P = 0.028) for the Model for End
      Stage Liver Disease score and 0.984 (95%CI: 0.942-1.027, P = 0.023) for the
      Maddrey Discriminant Function score with the optimal cut off point of 30.5
      (sensitivity 1, specificity 0.937) and 108.68 (sensitivity 1, specificity 0.969),
      respectively. Accordingly, for 90-d mortality the Area Under the Curve was 0.762
      (95%CI: 0.559-0.965, P = 0.065) for the Model for End-Stage Liver Disease score
      and 0.752 (95%CI: 0.465-1.038, P = 0.076) for the Maddrey Discriminant Function
      score with the optimal cut off point of 19 (sensitivity 0.6, specificity 0.6) and
      92 (sensitivity 0.6, specificity 0.946), respectively. The observed Kaplan Meier
      survival rates for different score-categories were compared with log-rank tests
      and higher score values were correlated with a lower survival. CONCLUSION:
      Equivalency of the Model for End-Stage Liver Disease and the Maddrey Discriminant
      Function score is implied by the current study, verified by the plotted Receiver
      Operative Curves and the estimated survival rates. A statistically significant
      utility of C-reactive protein, fibrin degradation products and alanine
      aminotransferase as independent predictors of 90-d mortality has also been
      verified.

PMID- 16810752
TI  - A pilot randomized control study to evaluate endoscopic resection using a
      ligation device for rectal carcinoid tumors.
AB  - AIM: Rectal carcinoid tumors smaller than 10 mm can be resected with local
      excision using endoscopy. In order to remove rectal carcinoid tumors completely,
      we evaluated endoscopic mucosal resection with a ligation device in this pilot
      control randomized study. METHODS: Fifteen patients were diagnosed with rectal
      carcinoid tumor (less than 10 mm) in our hospital from 1993 to 2002. There were 9
      males and 6 females, with a mean age 61.5 years (range, 34-77 years). The
      patients had no complaints of carcinoid syndrome symptoms. Fifteen patients were
      randomly divided into 2 groups: 7 carcinoid tumors were treated by conventional
      endoscopic resection, and 8 carcinoid tumors were treated by endoscopic resection
      using a ligation device. RESULTS: All rectal carcinoid tumors were located at the
      middle to distal rectum. The size of the tumors varied from 3 mm to 10 mm and
      background characteristics of the patients were not different in the two groups.
      The rate of complete removal of carcinoid tumors using a ligation device (100%,
      8/8) was significantly higher than that of conventional endoscopic resection
      (57.1%, 4/7). The three patients had tumor involvement of deep margin, for which
      additional treatment was performed. No complications occurred during or after
      endoscopic resection using a ligation device. All patients in the both groups
      were alive during the 3-year observation period. CONCLUSION: Endoscopic resection
      using a ligation device is a useful and safe method for resection of small rectal
      carcinoid tumors.

PMID- 16810753
TI  - Histologic characteristics of gastric polyps in Korea: emphasis on discrepancy
      between endoscopic forceps biopsy and endoscopic mucosal resection specimen.
AB  - AIM: To investigate histological characteristics of gastric polyps in the Korean
      population. METHODS: We reviewed endoscopic photographs and medical records of
      patients with gastric polyps who underwent endoscopic mucosal resection from
      April 1996 through February 2003. RESULTS: A total of 85 gastric polyps from 74
      patients were reviewed. Male-to-female ratio was 1:1.96. Mean age was 59.9 +/-
      10.8 years. Multiple polyps were observed in 10.8%. Gastric polyps occurred most
      frequently in the antrum (58.8%). Pathological results on resected specimens were
      as follows: tubular adenoma 45.9%, hyperplastic polyp 31.8%, inflammatory polyp
      9.4%, hamartoma 3.5%, fundic gland polyp 2.4%, tubulovillous adenoma 2.4%,
      adenocarcinoma 2.4%, dysplasia 1.1%, and mucosal pseudolipomatosis 1.1%.
      Discrepancy rate between endoscopic biopsy and pathology of resected specimens
      was 27.1%. There was no relationship between the size of the polyp and
      concordance rate. CONCLUSION: There is considerable discrepancy in histologic
      findings between endoscopic forceps biopsy and resected specimens. Approaches to
      review of the histology of an entire polyp should be performed, especially when
      an adenoma is suspected.

PMID- 16810754
TI  - A study on p53 gene alterations in esophageal squamous cell carcinoma and their
      correlation to common dietary risk factors among population of the Kashmir
      valley.
AB  - AIM: To systematically examine the extent of correlation of risk factors, such as
      age, consumed dietary habit and familial predisposition with somatic Tp53
      molecular lesion causal to elevate carcinogenesis severity of esophageal squamous
      cell carcinoma (ESCC) among the Kashmiri population of Northern India. METHODS:
      All cases (n = 51) and controls (n = 150) were permanent residents of the Kashmir
      valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor
      gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for
      individual cancer cases (n = 45) and inpatient controls (n = 150) with non-cancer
      disease included information on family history of cancer, thirty prevailing
      common dietary risk factors along with patient's age group. Correlation of
      genetic lesion in p53 exons to animistic data from these parameters was generated
      by Chi-square test to all 45 histologically confirmed ESCC cases along with
      healthy controls. RESULTS: Thirty-five of 45 (77.8%) histologically characterized
      tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample
      obtained from adjacent region from the same patient showed germline mutation. The
      SSCP analysis demonstrated that most common p53 gene alterations were found in
      exon 6 (77.7%), that did not correlate with the age of the individual and
      clinicopathological parameters but showed significant concordance (P<0.05) with
      familial history of cancer (CD = 58), suggesting germline predisposition at an
      unknown locus, and dietary habit of consuming locally grown Brassica vegetable
      "Hakh" (CD = 19.5), red chillies (CD = 20.2), hot salty soda tea (CD = 2.37) and
      local baked bread (CD = 1.1). CONCLUSION: Our study suggests that somatic
      chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer
      patients of an ethnically homogenous population of Kashmir valley are closely
      related to continued exposure to various common dietary risk factors, especially
      hot salty tea, meat, baked bread and "Hakh", that are rich in nitrosoamines and
      familial cancer history.

PMID- 16810755
TI  - Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism,
      Styela plicata.
AB  - AIM: To evaluate the antiviral effect of the effective ingredient of Styela
      plicata in a murine model of hepatitis B virus carrier. METHODS: HBV-transgenic
      mice were divided into 3 groups (control group, lamivudine treatment group and
      the effective ingredient of Styela plicata treatment group) and assigned to
      receive normal diet, lamivudine or the effective ingredient of Styela plicata for
      consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme
      linked immunosorbent assay (ELISA) method. Serum HBV DNA was detected by real
      time polymerase chain reaction (RT-PCR). Serum T helper (h) 1 cytokine
      interleukin (IL)-2 and Th2 cytokine IL-6 were detected by the quantitative
      sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was
      assigned to receive the effective ingredient of Styela plicata for consecutive
      weeks. The histology of liver tissue was evaluated before and after treatment.
      RESULTS: Twelve weeks after starting the therapy, serum hepatitis B surface
      antigen was significantly lowered in Styela plicata -treated mice and lamivudine
      treated mice compared with the mice receiving normal diet (F(12wk) = 88.81,
      P(12wk) = 0.000<0.01). Serum HBV DNA was significantly lowered in Styela plicata 
      treated mice and lamivudine-treated mice compared with the mice receiving normal
      diet (F(12wk) = 20.71, P(12wk) = 0.000<0.01). However, like lamivudine, the
      effective ingredient of Styela plicata could not inhibit the replication of HBV
      completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in
      sera could be found 4 wk after withdrawal of medication. Eight weeks after
      starting the therapy, serum levels before and after Styela plicata treatment of
      IL-2 were 2.41 +/- 0.38 and 10.56 +/- 0.78 ng/L, respectively (t(8wk) = -16.51,
      P(8wk) = 0.000<0.01). Compared with the serum levels of IL-2 in the normal diet
      treated mice (2.48+/-0.17 ng/L; t(8wk) = 13.23, P(8wk) = 0.000<0.01). Serum
      levels before and after Styela plicata treatment of IL-6 were 63.62 +/- 6.31 and
      54.52 +/- 6.22 ng/L, respectively, compared with the serum levels of IL-6 in the
      normal diet-treated mice (60.84 +/- 4.21 ng/L). Histological analysis of liver
      from Styela plicata-treated HBV-transgenic mice also showed catabatic status in
      inflammation and hepatitis B surface antigen. CONCLUSION: Styela plicata may be
      an effective antiviral medicine in treating chronic hepatitis B.

PMID- 16810756
TI  - Detection of H. pylori antibody profile in serum by protein array.
AB  - AIM: To detect multiple H. pylori antibodies in serum samples of individuals who
      carry H. pylori by protein array. METHODS: Recombinant H. pylori antigens, urease
      B subunit (UreB), vacuolating toxin A (VacA) and cytotoxin associated gene A
      protein (CagA), were prepared and immobilized in matrixes on nitrocellulose
      membrane by robotics to bind the specific immunoglobulin G (IgG) antibodies in
      serum. Staphylococcus protein A (SPA) labeled by colloid gold was used to
      integrate the immuno-complex and gave red color signal. The scanner based on
      charge-coupled device (CCD) could collect the image signal and convert it into
      digital signal. RESULTS: When human IgG was printed on the membrane in increasing
      concentrations and incubated with immunogold, a linear dose response curve was
      obtained and the detection limit for IgG was about 0.025 ng. The cutoff values,
      which were defined as the mean grey level plus 3 times of standard deviation,
      were 27.183, 28.546 and 27.402, for anti-UreB IgG, anti-CagA IgG and anti-VacA
      IgG, respectively, as 400 human serum samples with negative H. pylori antibodies
      were detected by the protein array. When 180 serum samples from patients in
      hospital were employed for detection of IgG against UreB, CagA and VacA, the
      sensitivity of the protein array was 93.4%, 95.4%, 96.0%, and the specificity was
      94.8%, 94.4% and 97.5%, respectively, as compared with the results obtained by
      ELISA. The assay also showed high reproducibility, uniformity and stability, and
      the results were available within 30 min. CONCLUSION: The protein array is a very
      practical method for rapid detection of multiple antibodies in serum samples. It
      is especially useful for large scale epidemiological investigation of the
      infection of H. pylori.

PMID- 16810757
TI  - Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in
      cirrhotic patients undergoing liver transplantation.
AB  - AIM: To investigate the perioperative changes of nitric oxide (NO) and endothelin
      (ET), thromboxane A2 (TXA2) and prostaglandin (PGI2) during liver transplantation
      in end-stage liver disease patients. METHODS: Twenty-seven patients with end
      stage cirrhosis undergoing liver transplantation were enrolled in this
      prospective study. Blood samples were obtained from superior vena at five
      different surgical stages. Plasma concentrations of nitrate and nitrite were
      determined to reflect plasma NO levels. Plasma levels of ET-1,6-keto-PGF1 alpha
      and thromboxane B2 (TXB2), the latter two being stable metabolites of PGI2 and
      TXA2 respectively, were measured. RESULTS: The NO level decreased significantly
      after vascular cross-clamping and increased significantly at 30 min after
      reperfusion. While the ET levels at 30 min after clamping and after reperfusion
      were significantly elevated. The ratio of NO/ET decreased significantly at 30 min
      after vascular cross-clamping and at the end of surgery. The PGI2 level and the
      TXA2 during liver transplantation were significantly higher than the baseline
      level, but the ratio of TXA2/PGI2 decreased significantly at 30 min after
      clamping. CONCLUSION: NO/ET and TXA2/PGI2 change during liver transplantation.
      Although the precise mechanism remains unknown, they may play a role in the
      pathobiology of a variety of liver transplant-relevant processes.

PMID- 16810758
TI  - Mistletoe alkali inhibits peroxidation in rat liver and kidney.
AB  - AIM: To explore the antioxidant and free radical scavenger properties of
      mistletoe alkali (MA). METHODS: The antioxidant effect of mistletoe alkali on the
      oxidative stress induced by carbon tetrachloride (CCl4) in rats was investigated.
      The rats were divided into four groups (n = 8): CCl4-treated group (1 mL/kg body
      weight), MA -treated group (90 mg/kg), CCl4+MA-treated group and normal control
      group. After 4 wk of treatment, the level of malondialdehyde (MDA), a lipid
      peroxidation product (LPO) was measured in serum and homogenates of liver and
      kidney. Also, the level of glutathione (GSH), and activities of glutathione
      reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), and
      glutathione-S-transferase (GST) in liver and kidney were determined. Scavenging
      effects on hydroxyl free radicals produced in vitro by Fenton reaction were
      studied by ESR methods using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin
      trap reagent and H2O2/UV as the OH. source. Urinary 8-hydroxydeoxyguanosine (8
      OHdG) was determined by competitive ELISA. RESULTS: In CCl4-treated group, the
      level of LPO in serum of liver and kidney was significantly increased compared to
      controls. The levels of GSH and enzyme activities of SOD, GSPx and GR in liver
      and kidney were significantly decreased in comparison with controls. In CCl4+MA
      treated group, the changes in the levels of LPO in serum of liver and kidney were
      not statistically significant compared to controls. The levels of SOD, GSPx and
      GR in liver and kidney were significantly increased in comparison with controls.
      There was a significant difference in urinary excretion of 8-OHdG between the
      CCl4-treated and MA-treated groups. CONCLUSION: Oxidative stress may be a major
      mechanism for the toxicity of CCl4. MA has a protective effect against CCl4
      toxicity by inhibiting the oxidative damage and stimulating GST activities. Thus,
      clinical application of MA should be considered in cases with carbon
      tetrachloride-induced injury.

PMID- 16810759
TI  - Expression of T-STAR gene is associated with regulation of telomerase activity in
      human colon cancer cell line HCT-116.
AB  - AIM: To investigate the effects on telomerase activity of transfection of human T
      STAR gene full-length sense cDNA or partial antisense cDNA into human colon
      cancer cell line HCT-116. METHODS: mRNA and protein expression levels of T-STAR
      gene were determined by RT-PCR and western blot, and telomerase activity was
      measured by PCR-ELISA, after transfection of T-STAR sense or antisense gene into
      HCT-116 cells with lipofectamine. RESULTS: T-STAR gene expression was enhanced or
      knocked down both at mRNA and protein levels, and telomerase activity was
      significantly increased or decreased. CONCLUSION: The T-STAR gene may participate
      in regulation of telomerase activity in human colon cancer HCT-116 cells in a
      parallel fashion.

PMID- 16810760
TI  - Dynamic changes of HBV DNA in serum and peripheral blood mononuclear cells of
      chronic hepatitis patients after lamivudine treatment.
AB  - AIM: To study the dynamic changes of hepatitis B virus (HBV) DNA in serum and
      peripheral blood mononuclear cells (PBMCs) of patients after lamivudine therapy.
      METHODS: A total of 72 patients with chronic HBV infection were included in this
      study. All patients were confirmed to have the following conditions: above 16
      years of age, elevated serum alanine aminotransferase (ALT), positive hepatitis B
      e antigen (HBeAg), positive HBV DNA in serum and PBMCs, negative antibodies
      against HAV, HCV, HDV, HEV. Other possible causes of chronic liver damages, such
      as drugs, alcohol and autoimmune diseases were excluded. Seventy-two cases were
      randomly divided into lamivudine treatment group (n = 42) and control group (n =
      30). HBV DNA was detected both in serum and in PBMCs by fluorescence quantitative
      polymerase chain reaction (PCR), during and after lamivudine treatment. RESULTS:
      In the treatment group, HBV DNA became negative both in serum and in PBMC, of 38
      and 25 out of 42 cases respectively during the 48 wk of lamivudine treatment, the
      negative rate was 90.5% and 59.5% respectively. In the control group, the
      negative rate was 23.3% and 16.7% respectively. It was statistically significant
      at 12, 24 and 48 wk as compared with the control group (P<0.005). The average
      conversion period of HBV DNA was 6 wk (2-8 wk) in serum and 16 wk (8-24 wk) in
      PBMC. CONCLUSION: Lamivudine has remarkable inhibitory effects on HBV replication
      both in serum and in PBMCs. The inhibitory effect on HBV DNA in PBMCs is weaker
      than that in serum.

PMID- 16810761
TI  - Intestinal permeability of metformin using single-pass intestinal perfusion in
      rats.
AB  - AIM: To characterize the intestinal transport and mechanism of metformin in rats
      and to investigate whether or not metformin is a substrate for P-glycoprotein (P
      gp). METHODS: The effective intestinal permeability of metformin was investigated
      using single-pass intestinal perfusion (SPIP) technique in male Waster rats. SPIP
      was performed in three isolated intestinal segments (duodenum, jejunum and ileum)
      at the same concentration of metformin (50 microg/mL) to test if the intestinal
      transport of metformin exhibited site-dependent changes, and in a same isolated
      intestinal segment (duodenal segment) at three different concentrations of
      metformin (10, 50, 200 microg/mL) to test if the intestinal transport of
      metformin exhibited concentration-dependent changes. Besides, P-gp inhibitor
      verapamil (400 microg/mL) was co-perfused with metformin (50 microg/mL) in the
      duodenum segment to find out if the intestinal absorption of metformin was
      affected by P-gp exiting along the gastrointestinal track. Stability studies were
      conducted to ensure that the loss of metformin could be attributed to intestinal
      absorption. RESULTS: The effective permeability values (P(eff)) of metformin in
      the jejunum and ileum at 50 microg/mL were significantly lower than those in the
      duodenum at the same concentration. Besides, P(eff) values in the duodenum at
      high concentration (200 microg/mL) were found to be significantly lower than
      those at low and medium concentrations (10 and 50 microg/mL). Moreover the co
      perfusion with verapamil did not increase the P(eff) value of metformin at 50
      microg/mL in the duodenum. CONCLUSION: Metformin could be absorbed from the whole
      intestine, with the main absorption site at duodenum. This concentration
      dependent permeability behavior in the duodenum indicates that metformin is
      transported by both passive and active carrier-mediated saturable mechanism. The
      P(eff) value can not be increased by co-perfusion with verapamil, indicating that
      absorption of metformin is not efficiently transported by P-gp in the gut wall.
      Furthermore metformin is neither a substrate nor an inducer of P-gp. Based on the
      P(eff) values obtained in the present study and using established relationships,
      the human fraction dose absorbed for metformin is estimated to be 74%-90% along
      human intestine.

PMID- 16810762
TI  - Inhibitory effect of fuzheng yiliuyin in combination with chemotherapeutics on
      human gastric carcinoma cell strain.
AB  - AIM: To study the inhibitory effects of fuzheng yiliuyin (Decoction for
      Suppressing Tumors by Strengthening the Body Resistance) in combination with
      chemotherapeutics on human gastric carcinoma cell strain. METHODS: Fuzheng
      yiliuyin (ZY) combined with various kinds of chemotherapeutics was put into two
      kinds of cultivated human gastric carcinoma cell strains, then its inhibitory
      effects on human gastric carcinoma cell strains were determined by the MTT
      method. Flow cytometer was used to assay the apoptosis rate, and the
      ultrastructure of gastric carcinoma cells was observed under transmission
      electron microscope. RESULTS: Obvious apoptosis was seen in gastric carcinoma
      cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic
      inhibition effects on the cultivated gastric carcinoma cells, but the effects
      were different on various cell strains. The inhibitory effects of ZY could be
      strengthened by cytotoxic action and apoptosis. ZY combined with fluorouracil,
      etoposide and cisplatin (EFP) chemotherapeutics had better inhibitory effects on
      SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better
      inhibitory effects than other drugs on MGC-803. CONCLUSION: ZY induces apoptosis
      and inhibits the growth of gastric carcinoma cells. ZY has the synergistic
      function of chemotherapeutics.

PMID- 16810763
TI  - Clinical and genetic characteristics of Chinese hereditary nonpolyposis
      colorectal cancer families.
AB  - AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis
      colorectal cancer (HNPCC) families and to screen the germline mutations of human
      mismatch repair genes hMLH1 and hMSH2 in the probands. METHODS: Thirty-one
      independent Chinese HNPCC families were collected in Zhejiang Province. All of
      them met Chinese HNPCC criteria. Clinical data about patient gender, site of
      colorectal cancer, age of onset, history of multiple colorectal cancer,
      associated extracolonic cancer were recorded. PCR and denaturing high performance
      liquid chromatography (DHPLC) were employed to screen the mutations. Sequencing
      analysis was used to find out the exact mutation site and characteristics of the
      samples showing abnormal DHPLC profiles. RESULTS: One hundred and thirty-six
      malignant neoplasms were found in 107 patients including 14 multiple cancers. One
      hundred and six of the 136 neoplasms (77.9%) were diagnosed as colorectal cancer,
      with an average age of onset at 48.57 +/- 29.00 years. Gastric cancer was the
      most common extracolonic cancer (10.3%) in these families. Twenty-three different
      sequence variations in hMLHl and hMSH2 genes were detected in these 17 families.
      Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent
      mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations.
      The latter seven mutations seemed to be pathogenic. CONCLUSION: Germline
      mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC
      kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some
      particular clinical characteristics, such as a left-sided predominance, less
      synchronous or metachronous colorectal cancer, and frequent occurrence of gastric
      cancer.

PMID- 16810764
TI  - In vitro screening of traditionally used medicinal plants in China against
      enteroviruses.
AB  - AIM: To search for new antiviral agents from traditional Chinese medicine,
      specifically anti-enteroviruses agents. METHODS: The aqueous extracts (AE) of
      more than 100 traditionally used medicinal plants in China were evaluated for
      their in vitro anti-Coxsackie virus B3 activities with a MTT-based colorimetric
      assay. RESULTS: The test for AE of 16 plants exhibited anti-Coxsackie virus B3
      activities at different magnitudes of potency. They can inhibit three steps
      (inactivation, adsorption and replication) during the infection. Among the 16
      plants, Sargentodoxa cuneata (Oliv.) Rehd. et Wils., Sophora tonkinensis Gapnep.,
      Paeonia veitchii Lynch, Spatholobus suberectus Dunn. and Cyrtomium fortunei J.
      sm. also have activity against other enterovirus, including Coxsackie virus B5,
      Polio virus I, Echo virus 9 and Echo virus 29. Cell cytotoxic assay demonstrated
      that all tested AE had CC50 values higher than their EC50 values. CONCLUSION: The
      sixteen traditionally used medicinal plants in China possessed antiviral
      activity, and some of them merit further investigations.

PMID- 16810765
TI  - Experimental and clinical study of influence of high-frequency electric surgical
      knives on healing of abdominal incision.
AB  - AIM: To study the influence of high-frequency electric surgical knives on healing
      of abdominal incision. METHODS: Two hundred and forty white rats were divided
      into 10(0), 10(2), 10(5), and 10(8) groups and rat models of abdominal operation
      were induced by using electric surgical knives and common lancets respectively.
      Then they were respectively given hypodermic injections of normal saline and 0.2
      mL quantitative mixture of Escherichia coli, Staphylococcus aureus and
      Pseudomonas aeruginosa at a concentration of 10(2), 10(5) and 10(8). On the basis
      of the animal experiment, 220 patients undergoing abdominal operations (above
      type II) were randomly allocated into one of following three groups: electric
      knife (EK, 93 cases), electro-coagulation (EC, 55 cases) and control (72 cases).
      High-frequency electric surgical knives were used to dissect abdominal tissues
      and electro-coagulation for hemostasis in EK group. Common lancets and electro
      coagulation were applied in EC group. Common lancets and tying silk suture were
      used in the controls. RESULTS: In all the groups except group 10(0), infection
      rate of incisional wounds made by electric surgical knives were remarkably higher
      than that with common lancets. Furthermore, there were significant differences in
      groups 10(2), 10(5), and 10(8) (P<0.05), but not in group 10(0) (P>0.05) between
      EK and EC groups. Clinical studies showed a delayed wound healing in 16 cases
      (17.20%) in EK, 11 cases (16.36%) in EC and 2 cases (2.86%) in the control
      groups. A significant difference between EK and the control groups (chi2 = 8.57,
      P<0.01), and between EC and the control groups (chi2 = 5.66, P<0.05) was
      observed, but not between EK and EC (chi2 = 0.017, P>0.05). CONCLUSION: High
      frequency electric knives may remarkably delay abdominal incision healing. Its
      application should be minimized so as to reduce the possibility of postoperative
      complications.

PMID- 16810766
TI  - Whole-cell recordings of calcium and potassium currents in acutely isolated
      smooth muscle cells.
AB  - AIM: To record calcium and potassium currents in acutely isolated smooth muscle
      cells of mesenteric arterial branches in rats. METHODS: Smooth muscle cells were
      freshly isolated by collagenase digest and mechanical trituration with polished
      pipettes. Patch clamp technique in whole-cell mode was employed to record calcium
      and potassium currents. RESULTS: The procedure dissociated smooth muscle cells
      without impairing the electrophysiological characteristics of the cells. The
      voltage-gated Ca2+ and potassium currents were successfully recorded using whole
      cell patch clamp configuration. CONCLUSION: The method dissociates smooth muscle
      cells from rat mesenteric arterial branches. Voltage-gated channel currents can
      be recorded in this preparation.

PMID- 16810767
TI  - Acute liver failure due to natural killer-like T-cell leukemia/lymphoma: a case
      report and review of the literature.
AB  - Acute liver failure (ALF) is a medical emergency requiring immediate evaluation
      for liver transplantation. We describe an unusual case of a patient who presented
      with ascites, jaundice, and encephalopathy and was found to have ALF due to
      natural killer (NK)-like T cell leukemia/lymphoma. The key immunophenotype was
      CD2+, CD3+, CD7+, CD56+. This diagnosis, which was based on findings in the
      peripheral blood and ascitic fluid, was confirmed with liver biopsy, and was a
      contraindication to liver transplantation. A review of the literature shows that
      hematologic malignancies are an uncommon cause of fulminant hepatic failure, and
      that NK-like T-cell leukemia/lymphoma is a relatively recently recognized entity
      which is characteristically CD3+ and CD56+. This case demonstrates that liver
      biopsy is essential in diagnosing unusual causes of acute liver failure, and that
      infiltration of the liver with NK-like T-cell lymphoma/leukemia can cause acute
      liver failure.

PMID- 16810768
TI  - Situs inversus abdominus and malrotation in an adult with Ladd's band formation
      leading to intestinal ischaemia.
AB  - Situs inversus abdominus with rotational anomaly of the intestines is an
      extremely rare condition. Although intestinal malrotation has been recognized as
      a cause of obstruction in infants and children and may be complicated by
      intestinal ischaemia, it is very rare in adults. When it occurs in the adult
      patient, it may present acutely as bowel obstruction or intestinal ischaemia or
      chronically as vague intermittent abdominal pain. Herein, we present an acute
      presentation of a case of situs inversus abdominus and intestinal malrotation
      with Ladd's band leading to infarction of the intestine in a 32 year old woman.

PMID- 16810769
TI  - Gastric metastasis by lung small cell carcinoma.
AB  - Metastatic tumors of the gastrointestinal tract are rare. We describe a case of
      gastric metastasis due to primary lung cancer, revealed by an upper
      gastrointestinal endoscopy (UGIE). Haematogenous metastases to the stomach are a
      rare event. To our knowledge, only 55 cases have been described in the
      international literature. In these patients, the prognosis is very poor. We
      report herein a case of gastric metastasis by lung small cell carcinoma, with a
      review of the literature about this rare entity.

PMID- 16810770
TI  - Endoscopic management of intragastric penetrated adjustable gastric band for
      morbid obesity.
AB  - This report describes a case of successful endoscopic management of intragastric
      penetrated adjustable gastric band in a patient with morbid obesity. The
      favorable course of the case described here demonstrates that adjustable gastric
      bands in the process of migration need not be removed surgically in patients who
      are asymptomatic.

PMID- 16810771
TI  - Successful treatment for esophageal carcinoma with lung metastasis by induction
      chemotherapy followed by salvage esophagectomy: report of a case.
AB  - We here report a case of a 51-year-old man with lung metastasis from esophageal
      carcinoma that was initially treated by combination chemotherapy consisting of
      fluorouracil and nedaplatin. Because metastatic disease disappeared, salvage
      esophagectomy was performed. Although chest wall recurrence developed at the
      thoracotomy wound, prolonged survival of 48 mo was achieved by local tumor
      resection and additional chemotherapy. This combination chemotherapy is regarded
      as a promising and considerable treatment for metastatic esophageal carcinoma.

PMID- 16810772
TI  - Sonographic findings of acute appendiceal diverticulitis.
AB  - Preoperative images of acute appendiceal diverticulitis are rarely reported
      because of the difficulty of distinguishing appendiceal diverticulitis from other
      ileocecal diseases like acute appendicitis or cecal diverticulitis. We report a
      case of preoperatively diagnosed acute appendiceal diverticulitis. A 30-year-old
      female with a presumptive diagnosis of acute appendicitis from history and
      physical examination was admitted to our hospital. Ultrasound sonography showed
      inflamed appendiceal diverticula and inflammatory changes of the surrounding
      tissue. The swollen appendix was detected but its findings were slightly
      different from those of typical acute appendicitis in the following points. One
      difference was the thickened wall of the appendix, the other difference was the
      presence of air in the appendix. The patient underwent appendectomy and the
      pathological specimen revealed inflammatory changes of diverticula within the
      appendix.

PMID- 16810773
TI  - Small bowel anisakiosis: a report of two cases.
AB  - Small bowel stenosis is a serious complication of intestinal anisakiosis. The aim
      of this report is to investigate whether severe stenosis of the small intestine
      can be conservatively managed. We treated two patients with severe stenosis of
      the small intestine caused by anisakiosis. Surgical intervention was eventually
      performed on the 23rd and 35th in the hospital, respectively. Histopathological
      examination of the resected specimens revealed that the intestinal wall had been
      completely damaged by the inflammatory reaction of anisakiosis, and that the
      damage was irreversible, thereby suggesting that laparotomy is needed in cases of
      severe small bowel stenosis caused by intestinal anisakiosis, even if a long
      period of conservative treatment for the intestinal anisakiosis allowed the
      patient to pass successfully through the acute phase.

PMID- 16810774
TI  - An unusual cause of dyspnoea complicating right upper abdominal swelling.
AB  - A middle aged, non-addict male presented with right upper abdominal pain and
      swelling with respiratory distress. Examination revealed central cyanosis,
      bipedal pitting edema with prominent epigastric and back veins. Liver was
      enlarged, tender, spanned 20 cm without any splenomegaly or ascites. Other
      systems were clinically normal. Laboratory investigations showed
      polymorphonuclear leucocytosis with slightly deranged liver function. Abdominal
      ultrasonography showed an abscess in the right lobe of the liver with compressed
      inferior vena cava (IVC), middle and left hepatic veins. Arterial blood gas (ABG)
      documented hypoxia with orthodeoxia and air-contrast echocardiography was
      suggestive of an intrapulmonary shunt. A diagnosis of hepato-pulmonary syndrome
      (HPS) was made with near normal liver function secondary to amebic liver abscess.
      It reversed completely following successful treatment of the liver abscess.

PMID- 16810775
TI  - Space charge effect on the electrostatic collection of thoron decay products.
AB  - Investigations on electrostatic collection of thoron decay products as a function
      of field strength in a special source-electrode arrangement have been performed.
      Yields of the decay products vs. field strength were measured by solid state
      silicon and CR-39 track-etched detectors. Results show a significant space charge
      effect on the yield of collected products if an insulator is placed between the
      electrodes. The intensities of the collected thoron daughters are influenced
      strongly by the air stream present in the cell.

PMID- 16810776
TI  - Charles Schepens.

PMID- 16810778
TI  - Editorial.

PMID- 16810777
TI  - Enoxaparin versus unfractionated heparin in ST-elevation myocardial infarction.

PMID- 16810779
TI  - Meningococcal Meningitis with Particular Reference to Epidemiology and
      Pathogenesis.

PMID- 16810780
TI  - Reticulocytes and their Humoral Regulation.

PMID- 16810781
TI  - The Laboratory Diagnosis of Virus Infections of Man: a Review.

PMID- 16810782
TI  - The Distribution of Leucocytes on the Counting Chamber.

PMID- 16810784
TI  - Familial Intestinal Polyposis.

PMID- 16810783
TI  - The Colorimetric Determination of Glucose.

PMID- 16810786
TI  - Diethylene Glycol Poisoning: Report on Two Cases.

PMID- 16810785
TI  - Report on Two Species of the Genus Fusiformis obtained from Pathological Lesions
      in Man.

PMID- 16810787
TI  - Iron Metabolism.

PMID- 16810788
TI  - The Error of Colour Matching with Haldane's Haemoglobinometer.

PMID- 16810789
TI  - Rapid and Economical Rhesus Testing: A Trial of Chown's Capillary Tube Method.

PMID- 16810790
TI  - A Simplified Price-Jones Technique.

PMID- 16810791
TI  - The Inhibition of Acid Phosphatases by Formaldehyde and its Clinical Application
      for the Determination of Serum Acid Phosphatases.

PMID- 16810793
TI  - Chloral Hydrate Plates for the Inhibition of Swarming of Proteus.

PMID- 16810792
TI  - A Quantitative Precipitation Test for Syphilis.

PMID- 16810794
TI  - Normal and Abnormal Blood Coagulation: A Review.

PMID- 16810796
TI  - Suppurative Meningitis in the Newborn due to Coliform Bacilli.

PMID- 16810795
TI  - The Determination of Packed Cell Volume from Blood and Plasma Gravities in Indian
      Soldiers.

PMID- 16810797
TI  - The Use of Intrathecal Heparin in Conjunction with Streptomycin in the Treatment
      of Tuberculous Meningitis: Preliminary Report.

PMID- 16810798
TI  - A Standardized Modification of the Laughlen Test for Syphilis.

PMID- 16810799
TI  - Single-Sample Tests in the Differential Diagnosis of Jaundice.

PMID- 16810801
TI  - The Enumeration of Blood Platelets.

PMID- 16810800
TI  - The Estimation of Potassium by a Micro-Method.

PMID- 16810802
TI  - Modifications of the Weinbach Method for the Determination of Sodium in Serum.

PMID- 16810803
TI  - Giant-Cell or Temporal Arteritis: a Review.

PMID- 16810804
TI  - Temporal Arteritis: A Report of Three Cases.

PMID- 16810805
TI  - The Gastric Neutral-Red Excretion Test.

PMID- 16810806
TI  - The Feulgen Reaction Applied to Clinical Haematology.

PMID- 16810807
TI  - Haemostasis with an Easily Prepared Stable Thrombin Solution.

PMID- 16810808
TI  - Serological Aspects of Weil's Disease.

PMID- 16810809
TI  - Salmonella birkenhead: A New Salmonella Type Causing Food-Poisoning in Man.

PMID- 16810810
TI  - Penicillin Blood Levels After Injection of Solid and Semi-Fluid Oily Suspensions
      of Penicillin.

PMID- 16810811
TI  - Embolism after Penicillin-Oil-Beeswax.

PMID- 16810813
TI  - An Emergency Bottle for Dried Plasma.

PMID- 16810812
TI  - Another Way of Applying Immersion Oil.

PMID- 16810814
TI  - Estimation of Streptomycin and Penicillin in Blood.

PMID- 16810816
TI  - The Error of the Red Cell Count.

PMID- 16810815
TI  - The Errors of Some Haematological Methods as They Are Used in a Routine
      Laboratory.

PMID- 16810817
TI  - A Further Case of Anti-Lutheran Immunization, with Some Studies on its Capacity
      for Human Sensitization.

PMID- 16810818
TI  - Some Observations on Thiouracil Neutropenia, with Special Reference to the
      Sternal Marrow.

PMID- 16810819
TI  - Congenital Defects following Rubella: Reports of Two Cases, One of which Shows a
      Hitherto Undescribed Lesion.

PMID- 16810820
TI  - Studies on Tetanus Prophylaxis.

PMID- 16810821
TI  - The Value of Liquoid for Blood Culture.

PMID- 16810823
TI  - A Machine for Washing Wassermann Tubes.

PMID- 16810822
TI  - The Use of the Selective Inhibitory Action of Toluene on Coliform Bacilli in
      Routine Cultures.

PMID- 16810824
TI  - A Machine to Assist in Rhesus-Grouping.

PMID- 16810825
TI  - Erythropoiesis with Particular Reference to its Study by Biopsy of Human Bone
      Marrow: A Review.

PMID- 16810826
TI  - Estimation of Prothrombin in Dicoumarin Therapy.

PMID- 16810827
TI  - Prothrombin Time in Dicoumarol Therapy.

PMID- 16810828
TI  - Cellular Analysis of the Aspiration Lung Biopsy from Normal and Some Pathological
      Conditions.

PMID- 16810829
TI  - The Influence of Anticoagulants on Fibrin Network Formation.

PMID- 16810830
TI  - Intra-medullary Cyst of the Spinal Cord Due to the Cestode Multiceps Multiceps in
      the Coenurus Stage: Report of a Case.

PMID- 16810831
TI  - The Albumin/Globulin Ratio: A Technical Study.

PMID- 16810832
TI  - Measurement of the Glomerular Filtration Rate and the Effective Renal Plasma Flow
      Using Sodium Thiosulphate and p-Amino-Hippuric Acid.

PMID- 16810833
TI  - Bacterial Fibrinolysin, its Possible Therapeutic Application in Tuberculous
      Meningitis.

PMID- 16810834
TI  - Elution of an Incomplete Type of Antibody from the Erythrocytes in Acquired
      Haemolytic Anaemia.

PMID- 16810835
TI  - Survival after Transfusion of Rh-positive Erythrocytes Previously Incubated with
      Rh Antibody.

PMID- 16810836
TI  - Acquired Haemolytic Anaemia: Survival of Transfused Erythrocytes in Patients and
      Normal Recipients.

PMID- 16810837
TI  - The Microbiological Assay of Riboflavin and Nicotinic Acid in Urine.

PMID- 16810838
TI  - The Determination of the Total Neutral 17-Ketosteroids in Urine.

PMID- 16810839
TI  - The Value of Diluted Antigen in the Wassermann Reaction.

PMID- 16810840
TI  - Coliform Infection of the Urinary Tract.

PMID- 16810841
TI  - A Simplified Procedure for Blood Cell Counts and Haemoglobin Determination.

PMID- 16810842
TI  - Rapid Determination of the Sickle Cell Trait by the Use of a Reducing Agent.

PMID- 16810843
TI  - The Photochemical Production of Gold Sols, Using Artificial Light.

PMID- 16810844
TI  - Orthotolidine Hydrochloride Test for Blood in Urine.

PMID- 16810845
TI  - The Mass Staining of Paraffin Sections Before the Removal of Wax.

PMID- 16810846
TI  - An Improved Swab for the Detection of Threadworm Ova.

PMID- 16810847
TI  - The Nature of Russell Bodies and Kurloff Bodies: Observations on the
      Cytochemistry of Plasma Cells and Reticulum Cells.

PMID- 16810848
TI  - Cystic Pneumatosis of the Large Intestine.

PMID- 16810849
TI  - The Surgical Pathology of Rectal Cancer.

PMID- 16810850
TI  - The Iron Reserve of a Normal Man.

PMID- 16810852
TI  - Serum Copper Levels in Pregnancy and Pre-Eclampsia.

PMID- 16810851
TI  - Serum Proteins: A Review.

PMID- 16810853
TI  - Latent Carcinoma of the Prostate.

PMID- 16810854
TI  - The Use of Pancreatic Extract as a Growth Stimulant for C. Diphtheriae.

PMID- 16810855
TI  - Errors in the Estimation of Streptomycin in Serum.

PMID- 16810856
TI  - Studies in vitro on Maturation of Erythroblasts in Normal and Pathological
      Conditions.

PMID- 16810857
TI  - Dextran as a Medium for the Demonstration of Incomplete Anti-Rh-Agglutinins:
      (Preliminary Report).

PMID- 16810858
TI  - Haemolytic Anaemia.

PMID- 16810859
TI  - Estimation of p-Aminosalicylic Acid in Blood.

PMID- 16810860
TI  - Concentration of Megaloblasts: An Aid in the Diagnosis of Pernicious Anaemia.

PMID- 16810861
TI  - Branch Reports.

PMID- 16810862
TI  - The Serum Tryptophane-Perchloric Acid Reaction as a Measure of Tissue
      Destruction.

PMID- 16810863
TI  - Effect of Para-amino-salicylic Acid on Prothrombin Time.

PMID- 16810864
TI  - Dried Disc Technique for Determining Sensitivity to the Antibiotics.

PMID- 16810865
TI  - Hypopituitarism in a Male due to Giant Cell Granuloma of the Anterior Pituitary.

PMID- 16810866
TI  - The Consumption of Prothrombin during Coagulation: The Defect in Haemophilia and
      Thrombo-Cytopenic Purpura.

PMID- 16810867
TI  - Urinary Excretion of Carbonic Anhydrase: A Simple Test for the Detection of
      Intravascular Haemolysis.

PMID- 16810868
TI  - Fortuitous Factors Affecting the Leucocyte Count in Blood from the Ear.

PMID- 16810869
TI  - The Identification of Barbiturate Drugs in Gastric Contents and Urine.

PMID- 16810870
TI  - Multiple Marrow Cultures from a Single Aspirate.

PMID- 16810871
TI  - An Easy Technique for Rh Grouping.

PMID- 16810872
TI  - A Multiple Manual Register for Differential Leucocyte Counts.

PMID- 16810873
TI  - Blood Pipette Shaking Machine.

PMID- 16810874
TI  - A Mechanical Aid in Making Blood Films.

PMID- 16810875
TI  - Association of Clinical Pathologists: 43rd Scientific Meeting.

PMID- 16810876
TI  - Techniques for the Evaluation of Adrenal Cortical Function by the Use of
      Adrenocorticotrophin: A Review.

PMID- 16810877
TI  - Meningeal Tumours: a Review.

PMID- 16810878
TI  - Two Cases of Human Infestation by Larvae of Linguatula serrata.

PMID- 16810879
TI  - Giant Cell Granuloma Associated with Lesions resembling Polyarteritis Nodosa.

PMID- 16810880
TI  - The Bone Marrow in Hutchison's Syndrome.

PMID- 16810881
TI  - A Complement Fixation Test for Herpes Simplex Infections.

PMID- 16810882
TI  - Determination of Bilirubin with Precipitation of the Plasma Proteins.

PMID- 16810883
TI  - Serum Protein Fractions: A Comparison of Precipitation Methods with
      Electrophoresis.

PMID- 16810884
TI  - The Fractionation of Serum Proteins using Sodium Sulphate.

PMID- 16810885
TI  - The Renal Threshold for Bilirubin.

PMID- 16810886
TI  - The Nature of the Tissue Fluid in the Oedema of Toxaemia of Pregnancy.

PMID- 16810887
TI  - A Simple Visual Turbidimetric Estimation of Serum Gamma Globulin.

PMID- 16810888
TI  - The Gravimetric Determination of Pregnanediol in Urine.

PMID- 16810889
TI  - A Simple Estimation of Salicylate in Serum.

PMID- 16810890
TI  - The Laboratory Diagnosis of Haemophilia.

PMID- 16810891
TI  - The Common Causes of Lymphopenia.

PMID- 16810892
TI  - The Plasma Viscosity.

PMID- 16810893
TI  - Creatine and Guanidoacetic Acid Metabolism in Pituitary Disease.

PMID- 16810894
TI  - Some Effects of Nitrates in Bacteriological Media.

PMID- 16810895
TI  - A Plate Test for Nitrate Reduction.

PMID- 16810896
TI  - The Destructive Effect of Traces of Zinc Salts on Complement.

PMID- 16810897
TI  - A Magnetically Operated Blood Cell Pipette Shaker.

PMID- 16810899
TI  - A Simple Inoculation Rack and Modified Technique for Rapid Subculturing and
      Antibiotic Testing.

PMID- 16810898
TI  - Blood Pipette Shaking Machine Mark II.

PMID- 16810900
TI  - Association of Clinical Pathologists: 44th Scientific Meeting.

PMID- 16810901
TI  - A Review of Modern Methods in Histochemistry.

PMID- 16810902
TI  - A Screening Test for Heterophile Antibodies in Infectious Mononucleosis.

PMID- 16810903
TI  - A Preliminary Report on a Modified Friedman Pregnancy Test.

PMID- 16810904
TI  - Association of Clinical Pathologists: 45th Scientific Meeting.

PMID- 16810905
TI  - The Normal Platelet Count in Man.

PMID- 16810906
TI  - Plasmacytosis in the Bone Marrow in Rheumatoid Arthritis.

PMID- 16810907
TI  - Emergency Methods for Rhesus Group Determination.

PMID- 16810908
TI  - The Estimation of Dicoumarin in Blood.

PMID- 16810909
TI  - Improved Culture Methods for the Detection of Ps. pyocyanea.

PMID- 16810910
TI  - The Effects of Heat and Sodium Ethyl Mercuri-thio-salicylate on the
      Staphylocoagulase Test.

PMID- 16810911
TI  - The Excretion of Pregnanediol and 17-Ketosteroids during the Menstrual Cycle in
      Benign Hirsutism.

PMID- 16810912
TI  - King-Armstrong Phosphatase Estimation by the Determination of Liberated
      Phosphate.

PMID- 16810914
TI  - A Photometric Method for the Estimation of Sodium.

PMID- 16810913
TI  - Micro-estimation of Plasma Iron with Orthotolidine.

PMID- 16810915
TI  - Whither Clinical Pathology?: Trends and Opportunities.

PMID- 16810916
TI  - Polyarteritis Nodosa and the "Rheumatic" Diseases.

PMID- 16810917
TI  - The Haemagglutination Reaction in Tuberculosis.

PMID- 16810919
TI  - The Determination of the Sensitivity of Myco. tuberculosis to Streptomycin.

PMID- 16810918
TI  - A Slide-culture Technique for Determining Streptomycin Sensitivity of M.
      tuberculosis in Sputum.

PMID- 16810920
TI  - The Proteolytic Enzyme Test for Detecting Incomplete Antibodies.

PMID- 16810921
TI  - The Effect of a Direct Electric Current on Normal and Antibody-sensitized Red
      Cells.

PMID- 16810922
TI  - The Effect of Citrovorum Factor (Folinic Acid) on Megaloblasts in vitro.

PMID- 16810923
TI  - The Reticulocyte Crisis after the Effective Specific Treatment of Pernicious
      Anaemia.

PMID- 16810924
TI  - The Sampling Error in Haemoglobin Determination.

PMID- 16810925
TI  - The Survival of Transfused Erythrocytes from Patients with Polycythaemia Vera.

PMID- 16810926
TI  - Combined Fragility Test for Congenital Haemolytic Jaundice.

PMID- 16810927
TI  - The Estimation of Sodium Gentisate in Plasma and Urine.

PMID- 16810929
TI  - An Improved Microscope Lamp.

PMID- 16810928
TI  - Potassium Levels in the Cerebrospinal Fluid after Death.

PMID- 16810930
TI  - A Useful Cover-slip Container.

PMID- 16810931
TI  - A Centrifugal Gradocol Filter.

PMID- 16810933
TI  - Association of Clinical Pathologists: 50th General Meeting.

PMID- 16810932
TI  - Association of Clinical Pathologists: 49th General Meeting.

PMID- 16810935
TI  - Association of Clinical Pathologists: 52nd General Meeting.

PMID- 16810934
TI  - Association of Clinical Pathologists: 51st General Meeting.

PMID- 16810936
TI  - Association of Clinical Pathologists: 53rd General Meeting.

PMID- 16810937
TI  - Association of Clinical Pathologists: 55th General Meeting.

PMID- 16810938
TI  - Association of Clinical Pathologists: 56th General Meeting.

PMID- 16810939
TI  - Association of Clinical Pathologists: 57th General Meeting.

PMID- 16810940
TI  - Association of Clinical Pathologists: 58th General Meeting.

PMID- 16810941
TI  - Comment on "The Estimation of Magnesium in Serum Using Titan Yellow".

PMID- 16810943
TI  - ASSOCIATION OF CLINICAL PATHOLOGISTS: 60th GENERAL MEETING.

PMID- 16810942
TI  - Association of Clinical Pathologists: 59th General Meeting.

PMID- 16810944
TI  - ASSOCIATION OF CLINICAL PATHOLOGISTS: 61st GENERAL MEETING.

PMID- 16810945
TI  - Seventh Congress of the International Society of Haematology.

PMID- 16810947
TI  - ASSOCIATION OF CLINICAL PATHOLOGISTS: 62nd GENERAL MEETING.

PMID- 16810946
TI  - BLANKET LAUNDERING AND STERILIZATION: REPORT OF A TRIAL AT THE CITY GENERAL
      HOSPITAL, SHEFFIELD.

PMID- 16810948
TI  - THE VALUE OF THE EXAMINATION OF THE CEREBROSPINAL FLUID IN THE DIAGNOSIS OF
      INTRACRANIAL TUMOURS.

PMID- 16810950
TI  - ASSOCIATION OF CLINICAL PATHOLOGISTS: 63rd GENERAL MEETING.

PMID- 16810949
TI  - A COMPARISON OF THE SHEEP CELL AND LATEX AGGLUTINATION TESTS IN RHEUMATOID
      ARTHRITIS.

PMID- 16810952
TI  - STANDARD BARIUM SULPHATE SUSPENSIONS.
AB  - It has been shown that the state of the volumetric flask, the order of mixing the
      reagents, and the temperature of the reaction are important influences on the
      optical density readings of standard barium sulphate suspensions. The rate of
      mixing the reagents does not appear to be important.A reproducible method for
      preparing a standard barium sulphate suspension with an optical density
      equivalent to 100 mg. protein per 100 ml. is described.

PMID- 16810951
TI  - CLINICAL AND PATHOLOGICAL FINDINGS IN OCHRONOSIS.
AB  - A case of ochronosis with far-advanced cardiovascular, skeletal, and prostatic
      manifestations is reported. An attempt is made to correlate the location of
      pigment with other pathological changes in this disorder. A brief discussion of
      the hereditary factors, the metabolic pathways of homogentisic acid, and the
      pathogenesis of ochronosis is presented.

PMID- 16810953
TI  - THE IDENTIFICATION OF A FLUORESCENT REDUCING SUBSTANCE IN THE URINE OF PATIENTS
      WITH RHEUMATOID ARTHRITIS: THE EXCRETION OF 3-HYDROXYANTHRANILIC ACID IN THIS AND
      OTHER CONDITIONS.
AB  - The report that 2,5-dihydroxyphenylpyruvic acid occurs in the urine of patients
      with collagen disease has not been confirmed, and no evidence was found for
      regarding collagen disease as being due to an inherent error in tyrosine
      metabolism as suggested by Japanese workers.A strongly reducing substance was
      conspicuous in the urine of patients with rheumatoid arthritis but not in that of
      normal persons. This substance was identified as 3-hydroxyanthranilic acid (3
      HAA).A method is described for the measurement of 3-HAA in urine, employing ether
      extraction, paper chromatography in a formate solvent, and visual assessment by
      fluorescence in ultra-violet light and colour with Ehrlich's reagent. Normal
      persons excreted from less than 125 to 375 mug./day (average rather lower than
      200 mug./day); those suffering from rheumatoid arthritis excreted from less than
      125 to 2,250 mug./day (average 820 mug./day). The excessive excretion of 3-HAA in
      persons with rheumatoid arthritis was investigated in terms of other aspects of
      the activity of the disease. Some relationship was suggested between excretion
      levels, the erythrocyte sedimentation rate, and the sensitized sheep cell test.
      Cases of osteoarthritis, other orthopaedic conditions, and miscellaneous diseases
      were examined. A few of the latter, including diseases of the haemopoietic
      system, were associated with increased excretion of 3-HAA.

PMID- 16810955
TI  - Seventh European Congress of Haematology.

PMID- 16810954
TI  - A Technique of Blood pH Estimation.

PMID- 16810956
TI  - THE INFLUENCE OF MECHANICAL FACTORS ON THE STRUCTURE OF THE PERIPHERAL ARTERIES
      AND THE LOCALIZATION OF ATHEROSCLEROSIS.
AB  - In a study of the peripheral arteries a period of development lasting until the
      end of the second decade of life is described. During this time there is evidence
      of medial hypertrophy and a continued formation of the longitudinal muscular
      cushions described in the foetus. Bands of longitudinal muscle also appear in the
      media of certain vessels. It is considered that the findings confirm the
      functional significance of foetal cushions and further suggest their relationship
      to the stresses of pulsation. In the later decades the tendency of
      atherosclerotic plaques to develop at the site of cushions is believed to reflect
      the importance of mechanical factors in the localization of this disease.

PMID- 16810957
TI  - THE ASSOCIATION OF CLINICAL PATHOLOGISTS.

PMID- 16810958
TI  - A COMPARISON OF THE ROSE-WAALER, LATEX FIXATION, "RA-TEST," AND BENTONITE
      FLOCCULATION TESTS.
AB  - The bentonite flocculation test of Bozicevich, Bunim, Freund, and Ward (1958),
      the latex fixation test of Singer and Plotz (1956), and the "RA-test" (a latex
      reagent for use as a slide test) of Hyland Laboratories have been compared with
      each other and with a modified Rose-Waaler test, the behaviour of which has been
      previously extensively investigated. In these tests sera from 2,250 patients were
      tested by two or more methods on 3,000 occasions. The findings of this trial are
      set out and the merits of the tests and reasons for disagreement among them are
      discussed. It is concluded that the most satisfactory means of testing rheumatoid
      sera is by the Rose-Waaler test and the "RA-test," or a satisfactory modification
      of it, in parallel.

PMID- 16810959
TI  - The Use of a Dyeline Photocopier in a Hospital Laboratory.

PMID- 16810960
TI  - SERUM HAPTOGLOBINS IN HAEMOLYTIC STATES.
AB  - Serum haptoglobin levels have been studied in patients with a number of
      haemolytic disorders. In general, serum haptoglobins were low in patients with
      increased haemolysis. Values were reduced irrespective of whether haemolysis
      occurred intravascularly or extravascularly. The reduction was related to the
      amount of haemoglobin destroyed per day. Serum haptoglobins may be raised in
      certain neoplasms and infections and during adrenocortical steroid hormone
      therapy. A rise in haptoglobins due to one of these factors may mask a fall due
      to haemolysis. Thus a normal or raised serum haptoglobin does not necessarily
      exclude a haemolytic process.

PMID- 16810961
TI  - MULTIPLE PRIMARY CANCERS: PRIMARY MALIGNANT LYMPHOMAS AND CARCINOMAS OF THE
      INTESTINAL TRACT IN THE SAME PATIENT.
AB  - Three cases of primary malignant lymphoma and primary mucus-secreting
      adenocarcinoma of the intestinal tract, occurring in the same patients, are
      described, and three similar cases reported in the literature are discussed. The
      carcinomas were present at the same time as the lymphomas, or developed after the
      lymphomas had been removed. The relationship between malignant lymphoma and
      carcinoma is uncertain, but there is some evidence to suggest a possible
      relationship between them. It is important not to assume that a second growth in
      the intestinal tract is always a recurrence or a metastasis from the original
      primary tumour.

PMID- 16810962
TI  - A New Method of Demonstrating Capsulated Bacillus anthracis.

PMID- 16810963
TI  - THE ASSOCIATION OF CLINICAL PATHOLOGISTS.

PMID- 16810964
TI  - NOMENCLATURE OF ABNORMAL HAEMOGLOBINS.

PMID- 16810965
TI  - Editorial.

PMID- 16810966
TI  - The Association of Clinical Pathologists.

PMID- 16810967
TI  - Control of infection in hospital wards.
AB  - Some of the problems of ward management are reviewed. Methods suggested for
      dealing with them are probably not the ideals that should ultimately be attained
      but minimum standards to serve as immediate objectives. They concern indications
      for and methods of isolation, control of infection from staff, environmental
      contamination, and a few technical procedures. A new type of dressing towel for
      wounds is described.

PMID- 16810968
TI  - Prevention of infection in operating theatres.

PMID- 16810969
TI  - A survey of staphylococci isolated in hospital practice.
AB  - In-patient and out-patient strains of coagulase-positive staphylococci were
      compared and showed a different phage group distribution. Group III predominated
      in the in-patient series and accounted for nearly all the antibiotic-resistant
      strains. The prevalence of phage type 80 in breast abscesses was noted. It was
      found that one in three coagulase-positive staphylococci isolated from hospital
      in-patients was sensitive to chloramphenicol and erythromycin only.

PMID- 16810970
TI  - Mortuary design and hazards.

PMID- 16810972
TI  - Symposium on anticoagulant therapy.

PMID- 16810971
TI  - The influence of penicillin on Lactobacillus leichmannii serum B(12) assay.
AB  - The influence of penicillin on vitamin B(12) assay using L. leichmannii as the
      test organism was investigated, and it was found that penicillin even in a low
      serum concentration invalidated the test.

PMID- 16810974
TI  - The Association of Clinical Pathologists.

PMID- 16810973
TI  - A family study of the biochemical defects in Wilson's disease.
AB  - Estimations of serum copper, serum ceruloplasmin (immunochemical), and urinary
      amino-acids excretion (quantitative and chromatographic) in 44 healthy relatives
      of patients with Wilson's disease (39 from one family) are reported. Each
      technique revealed some abnormal individuals. Good agreement was obtained between
      the serum copper and serum ceruloplasmin estimations and between the quantitative
      and chromatographic estimations of amino-acid excretion. Some individuals were
      abnormal to one or other of the pairs of tests only. These results cast doubt on
      the hypothesis that the symptoms of Wilson's disease are secondary to a
      quantitative (or qualitative) abnormality of ceruloplasmin. They also suggest
      that the mode of inheritance of the biochemical defects may be more complicated
      than that of a simple recessive mutant gene. Two of the relatives (one pregnant
      and one immediately post-partum) had a high serum copper level, as is expected in
      pregnancy, but normal serum ceruloplasmin. This suggests that the mechanism of
      control of the serum ceruloplasmin concentration may, normally, depend on the
      serum copper concentration.

PMID- 16810976
TI  - The iron method of haemoglobin estimation.

PMID- 16810975
TI  - Coccidiosis in guinea-pigs.
AB  - The attention of laboratory workers is drawn to the possibility of coccidiosis as
      a cause of death in guinea-pigs. The purchase of a number of guinea-pigs infected
      with this protozoon was followed by 12 deaths when these animals were injected
      with material for diagnostic purposes. No deaths occurred in the laboratory stock
      herd, as these were kept separate from the newcomers and were not infected. The
      life history of the parasite is described, together with the post-mortem findings
      in our series of animals.

PMID- 16810977
TI  - The histological diagnosis of toxoplasmic lymphadenitis.
AB  - The commonest presenting sign of acquired toxoplasmosis in man is enlargement of
      superficial lymph nodes. The persistence of the nodes may lead to a suspicion of
      malignant lymphoma and the diagnosis then hinges on the lymph node biopsy. Three
      cases of toxoplasmic lymphadenitis are described in each of which the diagnosis
      was unsuspected clinically. The chance discovery of a toxoplasma cyst in the
      lymph node section of Case 1 led to the correct diagnosis, after an initial
      diagnosis of Hodgkin's disease had been made. In the other two, strikingly
      similar histological changes in the lymph node biopsies suggested the diagnosis,
      which was confirmed serologically in each case. The histological changes are
      described and the clinical and pathological aspects of toxoplasmic lymphadenitis
      are briefly reviewed, with special reference to the differentiation from
      malignant lymphomatous conditions and to the specificity of the histological
      picture. It is concluded that the histology is, in many instances, sufficiently
      distinctive for a tentative diagnosis of toxoplasmic lymphadenitis to be made on
      the lymph node biopsy. The diagnosis should always be confirmed by isolation of
      the parasite or by serological tests. It is exceedingly rare for toxoplasma cysts
      to be found in lymph nodes and only one previous observation of this kind has
      been reported.

PMID- 16810979
TI  - The Association of Clinical Pathologists: Including joint meeting with
      Association of Clinical Biochemists.

PMID- 16810978
TI  - The diagnostic value of faecal trypsin estimation in chronic pancreatic disease.
AB  - Faecal trypsin levels have been estimated by a photometric azo-casein method in
      242 children and 45 adults. Analysis of the results shows that this is not a
      specific test of pancreatic dysfunction but that it appears to be a useful
      screening test for the selection of patients who may have severe pancreatic
      disease and on whom further specific investigations should be performed.

PMID- 16810980
TI  - A method for obtaining concentrates of eosinophils from blood.

PMID- 16810982
TI  - The Association of Clinical Pathologists.

PMID- 16810981
TI  - The nature of urinary casts.
AB  - The composition of hyaline casts has been investigated. The major constituent
      appears to be the urinary mucoprotein described by Tamm and Horsfall. Small
      amounts only of serum proteins are present. Neither the amounts excreted nor the
      concentration of Tamm-Horsfall protein appeared to determine the rate of cast
      formation. The only invariable association of hyaline cast formation was with the
      presence of significant amounts of serum proteins in the urine. In vitro it was
      found that aqueous solutions of serum albumin were particularly effective in
      producing precipitation of Tamm-Horsfall protein. This interaction was inhibited
      in normal urine but occurred to a greater extent in nephrotic urine and is
      suggested as the possible mechanism of hyaline cast formation.

PMID- 16810983
TI  - Editorial.

PMID- 16810984
TI  - The conflict of living matter with the mineral world: The pneumoconioses.

PMID- 16810985
TI  - Platelet aggregation: Part I Some effects of the adenosine phosphates, thrombin,
      and cocaine upon platelet adhesiveness.
AB  - PLATELETS IN NATIVE BLOOD ADHERE SPONTANEOUSLY TO GLASS INDEPENDENTLY OF
      TEMPERATURE: if adenosine diphosphate is added to the blood the adhesiveness of
      the platelets is increased and this effect is largely independent of temperature.
      The mono- and triphosphates decrease adhesiveness at 20 degrees C. and 37 degrees
      C. but have no effect at 0 degrees C.; cocaine inhibits adhesion at 37 degrees C.
      and at 0 degrees C. Aggregation and viscous metamorphosis of platelets in native
      plasma is induced at 37 degrees C. by adenosine diphosphate or by thrombin; these
      reactions do not occur at 0 degrees C. Cocaine and all the other anti-adhesive
      drugs inhibit thrombin or adenosine diphosphate-induced aggregation. The mono-
      and tri-phosphates appear to compete with adenosine diphosphate and inhibit
      aggregation; they also inhibit thrombin-induced aggregation. Aggregation induced
      by adenosine diphosphate or thrombin is not prevented by any of the usual enzyme
      inhibitors or uncoupling agents at the appropriate strength. At 37 degrees C.
      aggregation and viscous metamorphosis induced by adenosine diphosphate or
      thrombin are reversible, and the addition of more adenosine diphosphate or of
      thrombin again produces aggregation and viscous metamorphosis. Platelets
      incubated with adenosine diphosphate but not agitated lose their power to
      aggregate but when more adenosine diphosphate is added with agitation, then
      aggregation is again produced. These observations are presumably explained by the
      finding that intact platelets, but not fragmented platelets, can inactivate
      adenosine diphosphate. From these results it is tentatively concluded that
      adhesion may involve intrinsic adenosine diphosphate in the platelet which may be
      activated by thrombin and inhibited by the added mono- or triphosphate. The anti
      adhesive drugs act in a different manner. These phenomena have a remarkable
      similarity to those concerning mitochondrial swelling.

PMID- 16810986
TI  - Platelet aggregation: Part II Some results from a new method of study.
AB  - The light transmitted through a suspension of platelets increases if the
      platelets aggregate. A method derived from this observation has been used to
      study the kinetics of platelet aggregation. Aggregation is more rapid at 37
      degrees C., with rapid stirring, with high concentrations of adenosine
      diphosphate, and a high platelet concentration; a decrease in any of these
      conditions slows the process.

PMID- 16810987
TI  - An epidemiological study of haemagglutination in hepatitis.
AB  - An epidemiological study of 36 U.S. Marines living in a barracks and exposed to
      infectious hepatitis was made, and the ability of their sera to agglutinate day
      old chick erythrocytes was found to be abnormally high in 52.8% of the group. The
      other groups of American Servicemen similarly exposed showed no such deviation
      from the normally expected incidence of raised titres. An unexplained, abnormally
      high incidence of raised titres was found in several control groups. The titres
      appeared to be unaffected to any significant degree by gamma globulin prophylaxis
      or yellow fever immunization.

PMID- 16810988
TI  - Muscle morphology in infantile protein malnutrition.
AB  - A study was made of the sartorius muscle in Jamaican infants dying of protein
      malnutrition. Total counts were made of muscle fibres and sub-sarcolemmal nuclei
      in transverse section and compared with controls.A striking pathology is found in
      severe cases. The muscle fibre is reduced to a size comparable with that of the
      foetus. Although there is a greatly increased concentration of cells, there is
      also degeneration and actual loss of fibres and of sub-sarcolemmal nuclei. The
      proportion of the area occupied by muscle bundles may be halved, and there is a
      marked relative increase in interstitial collagen. These changes profoundly
      affect the interpretation of the results of biochemical analysis.

PMID- 16810989
TI  - Resistance of Salmonella typhi to chloramphenicol: Part II The mechanism of
      resistance.
AB  - A study of the action of the culture filtrates of 10 strains of S. typhi
      resistant to chloramphenicol showed that two of the strains produced an
      extracellular substance which enabled a strain of S. typhi sensitive to
      chloramphenicol to grow in a mixture of the filtrate and the antibiotic. A study
      of the properties of this substance suggested that it was an enzyme.

PMID- 16810990
TI  - The dispersal of staphylococci in hospital wards.
AB  - The air of three hospital wards was examined frequently for staphylococci for a
      period of nearly four years using slit samplers. ;Broadcasts' of staphylococci
      into the air were observed with the air count rising well above the mean of 0.2
      staphylococcal particle per cubic foot and these broadcasts often appeared to be
      due to single patients. Eight of the 3,675 patients admitted to the wards
      possessed an ability to disperse staphylococci into the air of the wards which
      was markedly greater than normal. The actual dispersal about the ward appeared to
      be mediated by the bedclothes, for, when these were disturbed, large numbers of
      staphylococci were disseminated into the air.

PMID- 16810991
TI  - Serum tube identification of Candida albicans.
AB  - The production of filaments (germ tubes) by cells of Candida albicans in serum
      tubes permits presumptive identification to be made within two to three hours.
      The proportion of yeast-like cells forming filaments is progressively decreased
      with increasing cell concentration. The test is effective over a comparatively
      wide range of temperatures and using different types and concentrations of sera.

PMID- 16810992
TI  - The estimation of two alpha(1) glycoproteins (orosomucoid and another alpha(1)
      acid glycoprotein) in health and disease.
AB  - The normal values for orosomucoid and the alpha(1) acid glycoprotein of Schultze
      in young adults are reported, specifically estimated by an immunological
      technique. The use of purified orosomucoid as a standard allowed of absolute
      estimation of this protein. The alpha(1) acid glycoprotein is estimated relative
      to a standard normal serum. These proteins were estimated in the serum of eight
      patients after surgery. Both proteins rise markedly in the serum, the alpha(1)
      acid glycoprotein reaching peak concentration in two to three days, and falling
      again equally rapidly, the orosomucoid rising more slowly to reach a peak after
      four to seven days, and returning to normal values in 10 to 14 days. Estimations
      of serum levels in 24 patients with a variety of diseases show that the two
      proteins can vary independently; values as high as eight times normal were found
      for orosomucoid in Crohn's disease. In patients with proteinuria, orosomucoid is
      preferentially excreted in the urine. The losses of alpha(1) acid glycoprotein
      are, however, anomalous, being proportionately less than those of albumin,
      relative to the serum levels. The significance of these preliminary findings is
      discussed.

PMID- 16810993
TI  - Simplified quantitative methods for bacteriuria and pyuria.
AB  - Although pyelonephritis is a common disease, it escapes clinical detection in an
      undesirably high proportion of patients. The present unsatisfactory diagnostic
      position would be much improved by widespread screening of patients by simple yet
      reasonably accurate methods. Bacterial counts by the pour-plate technique and
      estimates of the white cell excretion per hour or day, while undoubtedly of
      diagnostic value, are probably unsuitable for use on a wide scale. In an attempt
      to find more convenient procedures a simplified stroke-plate method of bacterial
      counting and a simplified quantitative white cell count method were devised and
      applied to over 1,000 mid-stream urine samples from 398 patients. Good
      correlation was obtained between the simpler stroke-plate method of bacterial
      counting and the more time-consuming pour-plate method. The quantitative white
      cell procedure was a much more sensitive index of pyuria than wet-film
      microscopy, and comparison with the bacterial count results showed that it gave a
      useful indication of urinary infection. It is suggested that a quantitative
      bacterial count should replace non-quantitative culture methods when urinary
      infection is suspected and that the quantitative white cell count should be
      performed as a routine part of the initial clinical and laboratory assessment of
      all patients, followed by a bacterial count if pyuria is revealed. Experience has
      shown that routine urine microscopy by a precise method leads to the detection of
      many cases of occult urinary infection.

PMID- 16810994
TI  - The differentiation of Enterobacteriaceae infecting the urinary tract: A study in
      male paraplegics.
AB  - Methods adopted in a routine bacteriology laboratory for the rapid identification
      of Enterobacteriaceae isolated from urine are described. The incidence of various
      bacteria causing infection in paraplegics after catheterization of the bladder is
      recorded, Klebsiella accounting for the majority of infections caused by lactose
      fermenters and Providence for the majority of ;paracolon' infections. The
      importance of these bacteria in cross-infection is discussed.

PMID- 16810995
TI  - Bronchopulmonary moniliasis in the newborn.
AB  - Ten instances of bronchopulmonary moniliasis due to C. albicans in neonatal
      infants, 1 to 11 days of age, are described. The incidence was 1.05% out of a
      total of 947 consecutive necropsies on neonates. Diagnosis was established by
      morphological identification of the fungi. Seven cases were associated with
      inflammatory exudation. In three cases inflammation was absent. Infection
      secondary to monilial vaginitis in the mother appears to have been over
      emphasized. The more common mechanism appears to be aspiration after delivery.

PMID- 16810996
TI  - Familial histiocytic reticulosis (familial haemophagocytic reticulosis).
AB  - The clinical and pathological findings are recorded in two siblings who died in
      early infancy from familial histiocytic (;haemophagocytic') reticulosis. The
      nature of this condition is obscure but probably represents a primary
      histiocytosis. The only other family on record is that described by Farquhar and
      Claireaux (1952) and by Farquhar, Macgregor, and Richmond (1958).

PMID- 16810997
TI  - Modification of an extraction technique for estimation of Evans blue in plasma.

PMID- 16810998
TI  - The Association of Clinical Pathologists: 69th Meeting.

PMID- 16810999
TI  - Ninth International Congress of Haematology: NOMENCLATURE OF ABNORMAL
      HAEMOGLOBINS.

PMID- 16811000
TI  - Iron storage in human disease: Fractionation of hepatic and splenic iron into
      ferritin and haemosiderin with histochemical correlations.
AB  - The hepatic and splenic storage iron, including the relative distribution between
      ferritin and haemosiderin, was estimated in 130 necropsies including normal
      accident cases and cases with a variety of diseases. The storage iron was also
      examined histochemically. It was found that in the normal subjects, on the
      average, approximately 400 mg. of iron was stored in these two organs, somewhat
      more than half being present as ferritin iron. Increased storage iron was found
      in some cases of infection, malignancy, and in blood and hepatic diseases, while
      low stores were present in other cases with malignancy and in polycythaemia vera.
      Although there was a slight tendency in infections and malignant diseases for
      more of the storage iron to be present as haemosiderin than normally, the most
      important factor affecting the distribution of iron between ferritin and
      haemosiderin was the total storage iron concentration. With total storage iron
      less than 500 mug. per gram of tissue, more iron was stored as ferritin than
      haemosiderin, and with values above 1,000 mug. per gram more was stored as
      haemosiderin. The behaviour of storage iron in this respect was very similar both
      in the liver and in the spleen. Although the histological and chemical estimates
      of the storage iron showed a general agreement there was much variation and
      histological examination of the tissues gave only a very approximate idea of the
      storage iron levels.

PMID- 16811001
TI  - Malignant melanoma of the anal canal.
AB  - The clinical and pathological features of 15 cases of malignant melanoma of the
      anal canal are described. It would appear from this study that these tumours
      arise from squamous epithelium lining that part of the anal canal at or just
      above the line of the anal valves.

PMID- 16811002
TI  - Platelet counting using the Coulter electronic counter.
AB  - A method for counting platelets in dilutions of platelet-rich plasm using the
      Coulter electronic counter is described.(1) The results obtained show that such
      platelet counts are at least as accurate as the best methods of visual counting.
      The various technical difficulties encountered are discussed.

PMID- 16811004
TI  - A double sampler unit for the Auto Analyzer.

PMID- 16811003
TI  - Rapid whole-blood platelet counting using an electronic particle counter.

PMID- 16811005
TI  - Muco-epidermoid tumours of the anal canal.
AB  - The pathology of 21 cases of muco-epidermoid carcinoma of the anal canal is
      described. These tumours are defined as squamous or transitional cell carcinomas
      containing areas which secrete mucin of undoubted epithelial origin within the
      clumps of tumour cells. They are found in that part of the anal canal just above
      the dentate line where the epithelium is variable in type and represents an
      embryological transition between rectal and squamous mucous membrane. The
      histogenesis of these tumours is discussed and the opinion given that they arise
      from the surface epithelium of the upper anal canal rather than from the anal
      glands.

PMID- 16811006
TI  - Wegener's granulomatosis: report of a patient surviving four and a half years.
AB  - A patient with Wegener's granulomatosis, treated with steroids on a long-term
      basis, survived at least four and a half years from onset until death occurred in
      an uncontrollable exacerbation of the disease process. This is believed to be the
      longest recorded survival.Histological examination of the necropsy specimens
      suggests that the basic pathological lesion in this disease is the subendothelial
      deposition of so far unidentified material in the capillaries, arterioles,
      venules, and smaller arteries. The associated angiitis may be a consequence of
      this deposition. These vascular lesions are occulusive and adequately account for
      the observed infarctive changes. The granulomatous features of the disease
      probably represent a secondary reactive phenomenon.

PMID- 16811007
TI  - Metaplasia of renal glomerular capsular epithelium.
AB  - Metaplastic changes in the renal glomerular epithelium is an unusual lesion. Only
      three other cases have been collected from the literature. This case is unique in
      that there was no associated liver disease.

PMID- 16811008
TI  - Further observations on platelet aggregation induced by adenosine diphosphate
      thrombin and tri-ethyl tin.
AB  - Aggregation induced by adenosine diphosphate is inhibited by adenosine as well as
      by adenosine mono- and triphosphate. Thrombin-induced aggregation is also
      inhibited by adenosine and the monophosphate, but the triphosphate at a similar
      concentration is not inhibitory. Aggregation induced by tri-ethyl tin is
      accelerated by a critical concentration of triphosphate and delayed by a higher
      concentration. The tri-ethyl tin effect is inhibited by 5-hydroxytryptamine and
      by tryptamine. Platelets from patients treated with reserpine respond normally to
      these last two substances. Incubated platelets lose first their ability to
      respond normally to tri-ethyl tin, then to thrombin, and lastly to adenosine
      diphosphate. These results are briefly discussed.

PMID- 16811009
TI  - Urea distribution in renal failure.
AB  - An assessment of intracellular urea removed during haemodialysis has been made
      from urea extraction and plasma urea estimations. An apparent wide variation in
      the movement of intracellular urea in patients with acute renal failure from
      obstetric and traumatic causes and with chronic renal failure is reported.A
      method for the estimation of red cell water urea is presented. In two patients
      with chronic renal failure the red cell urea level was much higher than would
      have been expected from the plasma urea level before dialysis. In two obstetric
      patients there was no such discrepancy. The conclusion is drawn that research
      should be directed to variations of intracellular metabolism in renal failure
      before a more rational approach can be made to its management.

PMID- 16811010
TI  - Sterilization of air filters for high pre-vacuum autoclaves.
AB  - Experiments are described with glass fibre filter paper and complete glass
      filters as fitted to high pre-vacuum autoclaves to determine whether organisms
      can grow or penetrate through the filters. A filter consisting of four layers of
      glass fibre paper fitted inside a sterilizer chamber for a year and used for 96
      sterilization cycles was found to have retained its initial efficiency.

PMID- 16811012
TI  - The Association of Clinical Pathologists: 70th general meeting.

PMID- 16811011
TI  - Comparison of colicine production and diffusion on different solid media.
AB  - Using a freezing-thawing method for extracting colicine from solid media it has
      been shown that the choice of media for production and diffusion is important.
      Digest nutrient agar yielded the most colicine and peptone water agar the least.
      A factor in bacteriological peptone, but absent in a proteose peptone (Difco) and
      Neopeptone, was responsible for inhibiting production on peptone water agar.
      Dextrose reduced the diffusion of colicine. A minimum of six hours' incubation of
      the colicinogenic organism was required for satisfactory production of colicine.

PMID- 16811014
TI  - BOOK RECEIVED.

PMID- 16811013
TI  - International enzyme units and isoenzyme nomenclature.

PMID- 16811015
TI  - Editorial.

PMID- 16811016
TI  - Association of Clinical Pathologists: 71st General Meeting.

PMID- 16811017
TI  - Fibrinolysis.

PMID- 16811018
TI  - Association of Clinical Pathologists: 72nd general meeting.

PMID- 16811019
TI  - BOOK RECEIVED.

PMID- 16811021
TI  - Association of Clinical Pathologists: 73rd general meeting.

PMID- 16811020
TI  - Folic acid clearances and basal serum folate levels in patients with thyroid
      disease.
AB  - The plasma clearance of intravenously administered folic acid was abnormally
      rapid in all of five patients studied with untreated hyperthyroidism; in three,
      the basal serum L. casei folate level was subnormal. Four of these patients and
      another patient were studied at various intervals after partial or complete
      correction of the hyperthyroid state. Partial correction resulted in a continued
      fast clearance in one patient, a return to borderline-normal values in the
      second, and a normal clearance in the third. Complete euthyroidism was achieved
      in two patients; their clearance values had returned to borderline-normal at this
      time. In two patients studied after partial correction, the serum L. casei folate
      levels had become normal whereas the clearance values remained abnormally rapid.
      These findings suggest that hyperthyroidism in man is associated with depletion
      of folate stores and subclinical deficiency of this vitamin. This is attributed
      to an increased demand for folic acid in the hypermetabolic state.

PMID- 16811022
TI  - Letter to the Editor.

PMID- 16811023
TI  - BOOK RECEIVED.

PMID- 16811024
TI  - The Association of Clinical Pathologists: 74th General Meeting.

PMID- 16811025
TI  - Chemical pathology in relation to clinical medicine RENAL FUNCTION: The
      proceedings of a symposium organized by the Association of Clinical Pathologists
      held in London at the Westminster Hospital 16-17 October 1964.

PMID- 16811026
TI  - Automatic determination of euglobulin lysis time.

PMID- 16811027
TI  - New reagent for the direct determination of serum cholesterol.

PMID- 16811028
TI  - The association of clinical pathologists: 75th general meeting.

PMID- 16811029
TI  - The Tunbridge Report and the laboratory.

PMID- 16811030
TI  - Preparation of bilirubin standards.

PMID- 16811031
TI  - Association of clinical pathologists: 76th general meeting.

PMID- 16811032
TI  - Analytical methods for steroids.

PMID- 16811033
TI  - Fragility of leucocytes in chronic lymphatic leukaemia.

PMID- 16811034
TI  - Cautionary tale.

PMID- 16811035
TI  - Serum aldolase and phosphocreatine kinase in umbilical cord blood.
AB  - Aldolase was estimated in the cord blood of 81 newborn infants and
      phosphocreatine kinase in 87 infants. There is a wide range in the results, with
      some values falling in the range reported in children with muscular dystrophy or
      of carriers of the disease. There is no correlation of the serum enzyme levels
      with the infant's birth weight. High levels of phosphocreatine kinase were found
      in infants of mothers with pre-eclamptic toxaemia. A single estimation of cord
      phosphocreatine kinase and aldolase is of little help in determining whether or
      not an infant has muscular dystrophy.

PMID- 16811037
TI  - Rapid concentration of proteins and electrolytes from frozen urine by
      centrifugation.

PMID- 16811036
TI  - Test for the presence of nitrate not involving carcinogenic reagents.

PMID- 16811038
TI  - The association of clinical pathologists: 77th general meeting.

PMID- 16811039
TI  - Extracts from the Presidential Address to the International Society of Clinical
      Pathology meeting in Rome.

PMID- 16811040
TI  - Transplantation of tissues and organs.

PMID- 16811041
TI  - Recognition of training laboratories.

PMID- 16811042
TI  - Histological features of the nephrotic syndrome associated with quartan malaria.

PMID- 16811043
TI  - Effect of diluents on blood clot lysis.

PMID- 16811044
TI  - Association of clinical pathologists: 78th general meeting.

PMID- 16811045
TI  - The Association of Clinical Pathologists: 79th general meeting.

PMID- 16811046
TI  - Obituary.

PMID- 16811047
TI  - 21st birthday.

PMID- 16811048
TI  - The Association of Clinical Pathologists: 80th general meeting.

PMID- 16811049
TI  - Thyroid function tests.

PMID- 16811050
TI  - ;Apparently barren regions' of the temporal bone.

PMID- 16811051
TI  - Mechanical rotary device for plating out.

PMID- 16811053
TI  - The Journal of Clinical Pathology-nine times a year!

PMID- 16811052
TI  - Urastrat.

PMID- 16811054
TI  - False positive curry's test.

PMID- 16811055
TI  - An evaluation of the Technicon AutoAnalyzer for automating complement-fixation
      tests.

PMID- 16811057
TI  - Reconditioned laboratory equipment.

PMID- 16811056
TI  - The problem of 'chronic mastitis' with epitheliosis.

PMID- 16811058
TI  - False Positive Curry's Test.

PMID- 16811059
TI  - Elastic changes and carcinoid.

PMID- 16811060
TI  - False-positive Reactions to Syphilis Tests.

PMID- 16811062
TI  - The journal in the 1970s.

PMID- 16811061
TI  - Blood levels in acute barbiturate poisoning.

PMID- 16811065
TI  - Epoxy resin sections.

PMID- 16811064
TI  - Effects of oestrogen and progestogen on serum levels of alpha(2)-macroglobulin,
      transferrin, albumin, and IgG.
AB  - The levels of four serum proteins, assayed by a radial immunodiffusion technique,
      have been measured in healthy women who had been given either the oestrogen or
      progestogen component of a combined oral contraceptive preparation for three
      weeks. Raised alpha(2)-macroglobulin and transferrin levels were found after
      oestrogen treatment but albumin and IgG did not significantly alter. In the
      progestogen-treated group all four proteins remained unchanged. The four proteins
      have also been assayed at frequent intervals during the normal menstrual cycle.
      No evidence of cyclical variation was found.

PMID- 16811066
TI  - Lymphangiosarcoma.

PMID- 16811067
TI  - Estimation of fibrinogen.

PMID- 16811068
TI  - Lysing agent for the coulter s.

PMID- 16811069
TI  - Problems related to fibrinolysis.

PMID- 16811070
TI  - Summary of three reports.

PMID- 16811071
TI  - Ortho fibrindex as a source of thrombim.

PMID- 16811072
TI  - Immunofluorescent technique for rapid virus diagnosis of cells in nasopharyngeal
      secretions.

PMID- 16811074
TI  - Klebsiella species in chest infections.

PMID- 16811073
TI  - Recruitment of pathologists for medical schools and hospitals in the tropics.

PMID- 16811075
TI  - Candida infections.

PMID- 16811077
TI  - A new year greeting.

PMID- 16811076
TI  - Coulter blood count.

PMID- 16811078
TI  - A review of the pathology and pathogenesis of acute renal failure due to acute
      tubular necrosis.

PMID- 16811079
TI  - ACP Broadsheet 80.

PMID- 16811063
TI  - The interpretation of the serum protein-bound iodine: A review.
AB  - The effects of physiological and environmental factors, of thyroid and non
      thyroid diseases, and of drugs on the serum protein-bound iodine are described
      and discussed.

PMID- 16811080
TI  - Incidence and Isolation of Bacteroides Species from Clinical Material and their
      Sensitivity to Antibiotics.

PMID- 16811082
TI  - Si units in pathology: the next stage.

PMID- 16811081
TI  - Symposium on anticoagulant control.

PMID- 16811083
TI  - Si units and concentration of glucose in cerebrospinal fluid.

PMID- 16811084
TI  - The relationship between urinary infection, cystoscopic appearance, and pathology
      of the bladder in man: II Squamous change in the bladder epithelium.
AB  - The occurrence of squamous change in the bladder epithelium was studied in
      bladder biopsies from patients with recurrent urinary infections or symptoms of
      cystitis and comparisons were made with sections taken at necropsy from control
      subjects. Two types of squamous change, termed ;vaginal' and ;cornified', are
      described. Vaginal change was frequent in females, and seemed to be a normal
      finding in them, but was not observed in males. It did not seem to be caused by
      urinary infection. Cornified change was also common in females and was found in
      one (infected) man. Like vaginal change it was most often found in sections from
      the trigone. Urinary infection may predispose to its formation but we were unable
      to prove this. Squamous change did not seem to cause symptoms, and could not
      usually be recognized at cystoscopy. The varieties described are so common that
      they are unlikely to be markedly precarcinomatous.

PMID- 16811085
TI  - Modification of an incident light microscope for fluorescence.

PMID- 16811086
TI  - Electrolyte serum reference samples.

PMID- 16811087
TI  - Elastofibroma.

PMID- 16811088
TI  - Malignant haemangioendothelioma involving the liver.

PMID- 16811090
TI  - Data-processing.

PMID- 16811089
TI  - Introduction.

PMID- 16811091
TI  - Coulter counter model ;s' system.

PMID- 16811092
TI  - More information please about commercial reagents.

PMID- 16811093
TI  - T cells in chronic lymphatic leukaemia.

PMID- 16811095
TI  - The Association of Clinical Pathologists: 96th general meeting.

PMID- 16811094
TI  - Quality control for coulter counter models.

PMID- 16811096
TI  - Alkaligenes faecalis in incubator humidifiers.

PMID- 16811097
TI  - Editorial.

PMID- 16811098
TI  - 2-Hydroxyethyl methacrylate for sectioning bone marrow.

PMID- 16811099
TI  - Macrophage electrophoretic mobility test.

PMID- 16811101
TI  - The Association of Clinical Pathologists: 97th general meeting.

PMID- 16811100
TI  - Plasma paracetamol estimation.

PMID- 16811103
TI  - The Association of Clinical Pathologists: 99th spring meeting.

PMID- 16811102
TI  - Pseudomembranous colitis.

PMID- 16811104
TI  - Editorial.

PMID- 16811105
TI  - Quality control in haemoglobin determination using the Coulter Counter S: a
      preliminary note.

PMID- 16811106
TI  - Cytological urine screening.

PMID- 16811107
TI  - Polystyrene mounting medium.

PMID- 16811109
TI  - Preservation of historic apparatus.

PMID- 16811111
TI  - Effect of bacterial flora on staphylococcal colonisation of the newborn.

PMID- 16811110
TI  - Thymidine mutants.

PMID- 16811112
TI  - An analysis of blood specimen container leakage.

PMID- 16811114
TI  - Uniform requirements for manuscripts submitted to biomedical journals.

PMID- 16811113
TI  - Recovery of spores from impregnated filter paper.

PMID- 16811115
TI  - The Association of Clinical Pathologists: 103rd Scientific Meeting: The 103rd
      Scientific Meeting was held in Reading, 5-6 April 1979. Abstracts of the
      scientific communications follow.

PMID- 16811116
TI  - Sense and safety in the laboratories.

PMID- 16811118
TI  - Bacillus cereus infections.

PMID- 16811117
TI  - Bacillus cereus infections.

PMID- 16811119
TI  - ;Ultra-fast' alkaline phosphatase isoenzyme.

PMID- 16811120
TI  - Serological diagnosis of mumps.

PMID- 16811121
TI  - Correlation between two commercial streptococcal grouping kits.

PMID- 16811122
TI  - Immunoperoxidase staining.

PMID- 16811123
TI  - Historic laboratory apparatus.

PMID- 16811124
TI  - Humphrey kay.

PMID- 16811125
TI  - UCH microbiology computer system.

PMID- 16811126
TI  - Polly-pica treated by xerography.

PMID- 16811127
TI  - Misapplication of Russell's name.

PMID- 16811129
TI  - The association of clinical pathologists: 106th scientific meeting.

PMID- 16811128
TI  - The association of clinical pathologists: 107th scientific meeting.

PMID- 16811131
TI  - Absorption spectra of pigments in vertebrate and non-vertebrate muscle.

PMID- 16811130
TI  - Classification of lymphoreticular malignancies.

PMID- 16811132
TI  - Role of the Schwartzmann reaction in necrotising enterocolitis.

PMID- 16811133
TI  - Photographic recording of the ESR.

PMID- 16811134
TI  - Effect of oxygen on the lungs after blast injury and burns.

PMID- 16811135
TI  - UK National microbiological quality assessment scheme.

PMID- 16811136
TI  - Demonstration of immunoproteins in Araldite-embedded tissues.

PMID- 16811137
TI  - Failure of growth on sensitivity testing agar.

PMID- 16811138
TI  - Screening method for mucopolysaccharidoses.

PMID- 16811139
TI  - The Howie code: is the price of safety too high?

PMID- 16811140
TI  - The Howie report and the Howie code.

PMID- 16811141
TI  - The Howie code: is the price of safety too high?

PMID- 16811142
TI  - Confusion of terms "birefringence" and "optical activity".

PMID- 16811143
TI  - Bacteriuria in patients undergoing prostatectomy.

PMID- 16811144
TI  - Detection of bacterial antigens in cerebrospinal fluid.

PMID- 16811145
TI  - The Howie code and the price of safety.

PMID- 16811146
TI  - Blood culture symposium.

PMID- 16811147
TI  - Mucosal prolapse syndrome.

PMID- 16811148
TI  - Is enrichment culture necessary for the isolation of Campylobacter jejuni from
      faeces?

PMID- 16811149
TI  - Continuous marker test for fat absorption.

PMID- 16811151
TI  - Histomorphometry of bone.

PMID- 16811150
TI  - Histomorphometry of bone.

PMID- 16811152
TI  - Dr Kaye comments.

PMID- 16811153
TI  - The pathology of meconium ileus equivalent.

PMID- 16811154
TI  - Alcohol induced liver disease.

PMID- 16811155
TI  - Adherence of neomycin to the tubing of a References plate pouring machine.

PMID- 16811156
TI  - Fine needle aspiration cytology.

PMID- 16811157
TI  - Measurements for haemoglobin.

PMID- 16811158
TI  - Streptococcus millerifound in pulmonary empyemas and abcesses.

PMID- 16811159
TI  - Guidelines on authorship: INTERNATIONAL COMMITTEE OF MEDICAL JOURNAL EDITORS.

PMID- 16811160
TI  - Arteritis of the epididymis.

PMID- 16811161
TI  - Is it time to rethink "high risk" labelling?

PMID- 16811162
TI  - Lymphocyte recovery rate using H6000.

PMID- 16811163
TI  - Cryptosporidium spa "new" human pathogen.

PMID- 16811164
TI  - Identifying "high risk" laboratory specimen's.

PMID- 16811165
TI  - Bios = life.

PMID- 16811166
TI  - Scar adenocarcinoma of the lung.

PMID- 16811167
TI  - Immunohistological detection of Legionella pneumophila in lung sections.

PMID- 16811168
TI  - Foreword.

PMID- 16811169
TI  - A Christmas thought from Professor NA Wright: HLA-DR expression in liver disease.

PMID- 16811170
TI  - Role of immunocytochemistry in diagnostic pathology: information from necrotic
      tissue.

PMID- 16811171
TI  - Troublesome Romanowsky stain deposits.

PMID- 16811172
TI  - Fetal volvulus and premature labour.

PMID- 16811173
TI  - Prospects for cure in acute leukaemia.

PMID- 16811174
TI  - Abstract: Association of Clinical Pathologists Research Award 1988:
      Undifferentiated cells in gastrointestinal mucosa inferring an association
      between carcinoma of the colon and intestinal type gastric cancer.

PMID- 16811175
TI  - Fungus ball of the urinary tract.

PMID- 16811176
TI  - Designation of "HPV" for human parvovirus.

PMID- 16811177
TI  - Tolerance to penicillin in streptococci of viridans group.

PMID- 16811178
TI  - Plus ca change..

PMID- 16811179
TI  - Peliosis thymomis.

PMID- 16811180
TI  - Eponym in pathology..

PMID- 16811181
TI  - Use of Tipp-Ex fluid as a marker of surgical resection margins.

PMID- 16811183
TI  - AgNOR staining in normal bone marrow cells.

PMID- 16811182
TI  - Measurement techniques for melanoma: a statistical comparison.

PMID- 16811184
TI  - Measurement techniques for melanoma: a statistical comparison.

PMID- 16811185
TI  - Editorial: Structured abstracts.

PMID- 16811187
TI  - Secretarial services to consultant microbiologists.

PMID- 16811186
TI  - Costing of pathology services in the United Kingdom National Health Service.

PMID- 16811188
TI  - John lilleyman editor 1986-1992.

PMID- 16811189
TI  - Post mortem sampling for biochemistry and toxicology.

PMID- 16811190
TI  - Speeding up necropsy reports.

PMID- 16811191
TI  - Aprocrine metaplasia: a new type of Mullerian metaplasia.

PMID- 16811192
TI  - T cell lymphoid aggregates in bone marrow in idiopathic hypereosinophilic
      syndrome.

PMID- 16811193
TI  - I read with interest the paper by..

PMID- 16811194
TI  - I read with interest the paper by..

PMID- 16811195
TI  - Fifty years of publication.

PMID- 16811196
TI  - Editorial.

PMID- 16811197
TI  - Continuing professional development: is the future Pathology Interactive?

PMID- 16811198
TI  - PIGEON WATER SUPPLY.

PMID- 16811199
TI  - Operant Extinction after Fixed-interval Reinforcement with Young Children.

PMID- 16811200
TI  - SPARK SUPPRESSION.

PMID- 16811201
TI  - TENSION-GAUGE.

PMID- 16811202
TI  - NEW INK FOR CUMULATIVE RECORDERS.

PMID- 16811203
TI  - A Simple System for Recording and Programming the Speed of Wheel Turning.

PMID- 16811204
TI  - A SIMPLE WAY TO RECORD LATENCIES.

PMID- 16811205
TI  - NEW TYPE OF CONNECTOR PLUGS AND SOCKETS.

PMID- 16811206
TI  - Probability Relations within Response Sequences under Ratio Reinforcement.

PMID- 16811207
TI  - A SIMPLE PULSE SHAPER.

PMID- 16811208
TI  - Preference and Switching under Concurrent Scheduling.

PMID- 16811209
TI  - Shock Intensity in Variable-interval Escape Schedules.

PMID- 16811210
TI  - A Source of Error in Estimating the Number of Reinforcements in a Lever-pressing
      Apparatus.

PMID- 16811212
TI  - Intermittent Reinforcement of a Complex Response in a Chimpanzee.

PMID- 16811211
TI  - Some effects of Two Temporal Variables on Conditioned Suppression.

PMID- 16811213
TI  - SCREW-ON MULTIPLE CONNECTORS.

PMID- 16811214
TI  - Some Notes on "Bursts" in Free-operant Avoidance Experiments.

PMID- 16811215
TI  - Operant Stuttering: the Control of Stuttering Behavior through Response
      contingent Consequences.

PMID- 16811217
TI  - Counting by Humans on a Fixed-ratio Schedule of Reinforcement.

PMID- 16811216
TI  - EDGE-MARKING OF RECORDING PAPER TO ELIMINATE CONFUSION OF RECORDS.

PMID- 16811218
TI  - A NEW SHOCK GRID FOR RATS.

PMID- 16811219
TI  - Some Effects of Noise on Human Behavior.

PMID- 16811220
TI  - A Simple Stabilimeter.

PMID- 16811221
TI  - The effect of methamphetamine on operant level and avoidance behavior.

PMID- 16811222
TI  - The effect of deprivation and frequency of reinforcement on variable-interval
      responding.

PMID- 16811223
TI  - Sequential dependencies of the lengths of consecutive response runs.

PMID- 16811224
TI  - Sustained performance during very long experimental sessions.

PMID- 16811225
TI  - Behavior under extended exposure to a high-value fixed interval reinforcement
      schedule.

PMID- 16811226
TI  - By-products of aversive control.

PMID- 16811227
TI  - Fixed-ratio schedules of conditioned reinforcement with chimpanzees.

PMID- 16811228
TI  - Interaction among components of a multiple schedule.

PMID- 16811229
TI  - The use of pinch as an aversive stimulus.

PMID- 16811230
TI  - A generalization gradient for auditory intensity in the rat.

PMID- 16811231
TI  - Intermittent reinforcement of operant behavior in children.

PMID- 16811232
TI  - Response to different degrees of novelty: the incidence of various activities.

PMID- 16811233
TI  - Effects of scopolamine on a multiple schedule.

PMID- 16811234
TI  - Some observations on an operant in human subjects and its modification by dextro
      amphetamine.

PMID- 16811235
TI  - The accentuation of a rate difference during extinction.

PMID- 16811236
TI  - Fixed-interval reinforcement of running in a wheel.

PMID- 16811237
TI  - Some time-correlated reinforcement schedules and their effects on behavior.

PMID- 16811238
TI  - The maintenance of behavior by the termination and onset of intense noise.

PMID- 16811239
TI  - Some neural and behavioral correlates of electrical self-stimulation of the
      limbic system.

PMID- 16811240
TI  - Some observations on an operant in the octopus.

PMID- 16811242
TI  - One bar-press per day: acquisition and extinction.

PMID- 16811241
TI  - A complex concurrent schedule of reinforcement.

PMID- 16811243
TI  - Some data on behavior reversibility in a steady state experiment.

PMID- 16811245
TI  - A Precision Liquid Feeding System Controlled by Licking Behavior.

PMID- 16811244
TI  - A notation system for the description of behavioral procedures.

PMID- 16811246
TI  - Some Electronic Control Units for Operant Behavior Studies: I. A Response and
      Reinforcement Contingency Translator.

PMID- 16811247
TI  - Human Observing Behavior after Signal Detection.

PMID- 16811248
TI  - The Aversive Control of an Operant Discrimination.

PMID- 16811250
TI  - A Simple Interval-Programming Circuit.

PMID- 16811249
TI  - Multiple Schedules of Time-Correlated Reinforcement.

PMID- 16811252
TI  - Intermittent Reinforcement of Discriminatively Controlled Responses and Runs of
      Responses.

PMID- 16811251
TI  - Behavior Stability Under Extended Exposure to a Time-Correlated Reinforcement
      Contingency.

PMID- 16811253
TI  - Stimulus Generalization as a Function of the Time between Training and Testing
      Procedures.

PMID- 16811254
TI  - Suggested French translations of expressions in the field of operant
      conditioning.

PMID- 16811255
TI  - Avoidance learning in dogs without a warning stimulus.

PMID- 16811256
TI  - The shape of some wavelength generalization gradients.

PMID- 16811257
TI  - Rapid development of multiple-schedule performances with retarded children.

PMID- 16811258
TI  - An analysis of interactions in a multiple schedule.

PMID- 16811259
TI  - A technique for measuring the latency of a discriminative operant.

PMID- 16811260
TI  - Stimulus generalization in an avoidance situation.

PMID- 16811261
TI  - Separation of two-channel recordings for vocal behavior studies.

PMID- 16811262
TI  - A method for the analysis and control of speech rate.

PMID- 16811263
TI  - An operant-discrimination apparatus for infants.

PMID- 16811264
TI  - Generalization of auditory intensity as a function of amount of discrimination
      training.

PMID- 16811265
TI  - Techniques of housing and maintaining a large pigeon colony.

PMID- 16811266
TI  - Effects of dl-amphetamine under concurrent VI DRL reinforcement.
AB  - Three adult, food-deprived rats were given IP injections of dl-amphetamine
      sulfate under DRL and concurrent VI DRL reinforcement schedules. The drug results
      were as follows.(1) The IRT distributions of DRL responses shifted to the left,
      but some temporal discrimination remained. (2) The IRT distributions of VI
      responses shifted slightly to the left. (3) The distinguishing characteristics of
      VI and DRL IRT distributions were preserved. (4) The frequency distribution of
      number of VI responses between two consecutive DRL responses was relatively
      unaffected. (5) Over-all response rates on the two components of the concurrent
      schedules increased more or less proportionately. These findings imply that the
      primary behavioral effect of dl-amphetamine was a motor excitatory one. The
      drug's disruption of timing behavior was not due to a derangement of internal
      timing mechanisms, nor to interference with the topography or pattern of
      behavior. Rather, it might be a secondary result of the accelerated emission of
      overt behavior patterns mediating the temporal spacing of DRL bar presses.

PMID- 16811267
TI  - Exteroceptive control of fixed-interval responding.
AB  - Two pigeons were exposed to several fixed-interval schedules of food
      reinforcement. In some cases, exteroceptive stimuli associated with the passage
      of time were present. Such visual "clock" stimuli were found to gain almost
      complete control over the behavior, although at the longest fixed interval
      studied, the superposition of a new temporal discrimination upon the visual
      discrimination was observed. Where clock stimuli were made contingent upon the
      birds' behavior, a new form of responding was generated. This behavior was
      discussed in terms of positive and negative response-tendencies resulting from
      several stimulus factors: Some of these functioned as S(Delta)'s and secondary
      negative reinforcers; some functioned as S(D)'s and secondary positive
      reinforcers; and some were ambiguous with respect to reinforcement conditions. A
      "pure temporal" discrimination was superimposed upon these factors, but its exact
      nature was indeterminate from the present data.

PMID- 16811269
TI  - A simple method for reliably coating intracranial electrodes.

PMID- 16811268
TI  - The alteration of behavior in a special classroom situation.
AB  - Unproductive classroom behavior was eliminated in two emotionally disturbed boys
      by removing social consequences of the behavior. Behavior which was more adequate
      and efficient with respect to social and scholastic adjustment was shaped and
      maintained with social reinforcers.

PMID- 16811270
TI  - A response key for use with projection-type display units.

PMID- 16811271
TI  - Continuous recordings of revolving-cage activity units.

PMID- 16811273
TI  - Photograph of first Conference on the Experimental Analysis of Behavior.

PMID- 16811272
TI  - Additional techniques for producing multiple-schedule control in children.
AB  - The subjects in these experiments were 132 children, varying in age from 4 to 7
      years. These experiments were designed to assess the efficacy of various multiple
      scheduling procedures in producing reliable stimulus control. The schedules
      studied were multiple fixed-ratio-extinction (mult FR EXT); multiple differential
      reinforcement-of-other-behavior-fixed-ratio (mult DRO FR); multiple differential
      reinforcement-for-low-rate-fixed-ratio (mult DRL FR); and multiple fixed-interval
      fixed-ratio (mult FI FR). In addition other techniques were investigated, such as
      presenting FR's in blocks; increasing the size of the FR's; attaching a DRL to
      the FI members; temporarily shifting to new schedules; and adding an external
      clock to the FI's. These experiments yielded the following results.1.) Strong
      stimulus control was produced by mult FR EXT, mult DRO FR, and mult DRL FR
      schedules. Control for mult FR EXT was mediated principally by the individual
      stimuli, though on occasion it was dependent in part on the change of stimuli.
      The mult DRO FR was found to be highly useful for those children who had very
      high initial rates or who were generally uncooperative and unmanageable.2.)
      Contrary to a previous finding, some subjects were brought under stimulus control
      by means of mult FI FR schedules without the aid of additional procedures. Most,
      however, were not. Additional techniques found to augment the development of mult
      FI FR control included: (1) presenting FR's in blocks; (2) increasing the size of
      the FR's; (3) attaching a DRL to the FI component for a time and later removing
      it; and (4) shifting to a mult DRL FR, developing control, and then returning to
      the original mult FI FR.3.) Addition of an external clock to the FI components of
      the mult FI FR had several effects. Strongest control, including well-developed
      acceleratory patterns during the FI's, was developed in those subjects who had
      first been shifted from a regular mult FI FR to a mult FR EXT, brought under
      control, and then returned to the mult FI FR with the clock added. The added
      clock also produced strong control if it was present when the subject was first
      begun on a mult FI FR schedule. In some cases, the addition of the clock produced
      control in subjects who had not been controlled previously by the regular mult FI
      FR, but these were always subjects who had high rates. The addition of the clock
      first lowered the rate, then produced control.

PMID- 16811274
TI  - Nonconsumption of the reinforcer under drug action.
AB  - Cats were trained to respond on a multiple discriminative schedule, with milk as
      reinforcement. Two subjects did not immediately consume the reinforcer when they
      were injected with 6 mg of methylphenidate before the experiment. This
      observation could be repeated in one of the subjects under various conditions of
      reinforcement and various doses of the drug. Control experiments showed that
      under normal conditions the same cats never ignored the reinforcer. The
      modification induced by the drug in the relationship between behavior and the
      reinforcement is discussed in its bearing on the notion of reinforcer.

PMID- 16811275
TI  - Acquisition of delayed matching in the pigeon.
AB  - Pigeons were exposed to three successive matching-to-sample procedures. On a
      given trial, the sample (red, green or blue light) appeared on a center key;
      observing responses to this key produced the comparison stimuli on two side keys.
      Seven different experimental conditions could govern the temporal relations
      between the sample and comparison stimuli. In the "simultaneous" condition, the
      center key response was followed immediately by illumination of the side key
      comparison stimuli, with the center key remaining on. In "zero delay" the center
      key response simultaneously turned the side keys on and the center key off, while
      in the "variable delay" conditions, intervals of 1, 2, 4, 10, and 24 sec were
      interposed between the offset of the sample and the appearance of the comparison
      stimuli on the side keys. In all conditions, a response to the side key of
      matching hue produced reinforcement, while a response to the non-matching side
      key was followed by a blackout. In procedure I all seven experimental conditions
      were presented in randomly permutated order. After nine sessions of exposure (at
      191 trials per session, for a total of 1719 trials) the birds gave no evidence of
      acquisition in any of the conditions. They were therefore transferred to
      Procedure II, which required them to match only in the "simultaneous" condition,
      with both the sample and comparison stimuli present at the same time. With the
      exception of one bird, all subjects acquired this performance to near 100%
      levels. Next, in Procedure III, they were once more exposed to presentation of
      all seven experimental conditions in random order. In contrast to Procedure I,
      they now acquired the delay performance, and were able to match effectively at
      delays of about 4 sec.

PMID- 16811276
TI  - Maze Experiment.

PMID- 16811277
TI  - A titration schedule on a treadmill.
AB  - A technique is presented utilizing a titration schedule to measure performance
      decrement as a function of continuing heavy muscular exertion. A treadmill is
      equipped with a reversible motor controlling the velocity control of the
      treadmill itself. This provides a constant acceleration of the treadmill unless a
      subject-controlled, spring loaded switch is depressed. If this switch is
      depressed, the treadmill decelerates at a constant rate. A subject is instructed
      to walk at maximum rate at all times, controlling the velocity of the treadmill
      with the switch. A performance record is obtained from a tachometer-generator on
      the treadmill delivering current to a recorder.

PMID- 16811278
TI  - Interresponse time as a function of continuous variables: a new method and some
      data.
AB  - A cathode-ray oscilloscope and a Polaroid camera record interresponse times as a
      function of time, stimulus wavelength, and similar variables. Each response
      flashes a point of light on the oscilloscope screen; the vertical position of the
      point gives IRT, the horizontal position gives the value of the other variable.
      Several thousand such points may be recorded on a single frame of film, and the
      density of the points indicates the relative frequency of various IRTs. The
      method has the advantages of a two-dimensional display of continuous variables,
      flexibility, speed, and relatively low cost. It lacks the advantage of a digital
      output. Figures show IRTs of pigeons on VI, FR, DRL and extinction, and
      transitions among these, and also the results of stimulus generalization tests.
      The results have some provocative features that require much further exploration.
      Among other things, they suggest that "response rate" as a measure usually
      includes a response-dependent component that is insensitive to changes in other
      variables.

PMID- 16811279
TI  - An improved live-worm dispenser.

PMID- 16811280
TI  - Effects of a concurrent task on fixed-interval responding in humans.
AB  - Subjects pressed a telegraph key to illuminate a meter dial on which pointer
      deflections appeared at fixed intervals. Upon detecting a deflection they were
      required to press another key to reset the pointer to zero. This detecting and
      resetting operation reinforced the behavior of pressing the light-flashing key
      (i.e., the observing responses). The usual pattern of responding on the light
      flashing key was a long pause following the reinforcement and an abrupt
      transition to a steady response rate toward the end of the interval. When the
      subjects were required to perform a concurrent subtraction task, the pattern of
      responding changed in varying degrees, ranging from complete loss of typical
      fixed-interval behavior to a slight shortening of the post-reinforcement pause.
      These effects were attributed to the disruption of the self-produced verbal
      chains (counting or reciting) that ordinarily govern human behavior on this
      schedule.

PMID- 16811281
TI  - Random interval schedules of reinforcement.
AB  - A method for generating a reinforcement schedule that closely approximates
      idealized VI schedules in which reinforcement assignments occur randomly in time
      (RI schedules) is described. Response rates of pigeons exposed for 20 sessions to
      this schedule appeared very similar to response rates characteristic of
      arithmetic series VIs. The distribution function describing these schedules was
      derived and its relations to other VI distributions, as well as to FI and random
      ratio (RR) were shown.

PMID- 16811282
TI  - Chained and tandem scheduling with children.
AB  - Children 4 to 7 yr in age were reinforced with trinkets and pennies on chained
      and tandem schedules. The schedules used were chain DRL FR, chain DRO FR, chain
      FI FR, tand FI FR, and tand DRO FR. Chain DRL FR and chain DRO FR schedules
      almost always produced strong schedule and stimulus control, but chain FI FR
      schedules rarely did if additional techniques were not used. Strong control was
      produced with chain FI FR schedules, however, if: (a) the FR component was
      increased in size; (b) schedule and stimulus control was first established with
      chain DRL FR or chain DRO FR schedules before shifting to the chain FI FR; or (c)
      an external clock was attached to the FI. Tand FI FR schedules never produced
      regular or repeatable patterns of responding when additional procedures were not
      used. Rate patterns resembling those of chain FI FR schedules were produced by
      tand FI FR schedules, however, if: (a) an external clock was attached to the FI
      component or (b) control was established by means of tand DRO FR schedules before
      the tand FI FR was used. Stimulus control was found to be exercised by specific
      visual stimuli, change of stimuli, and schedule order. Control exercised by
      schedule order was probably mediated by the child's own behavior which had
      assumed discriminative stimulus properties.

PMID- 16811283
TI  - Abstracts from SEAB Fall Conference: Stimulus generalization and inhibitory
      control the stimulus generalization of punishment.

PMID- 16811284
TI  - The effect of multiple S periods on responding on a fixed-interval schedule: IV.
      Effect of continuous S with only short S probes.
AB  - Pigeons were studied under FI 500 sec in which an S(Delta) was present throughout
      the interval except during the terminal 50-sec segment and one earlier 50-sec
      segment. Very little responding occurred during the presence of S(Delta). The
      rate of responding in the earlier 50-sec S(D) segments was lower than in the
      terminal S(D) segment. There was a clear trend for the rate of responding in the
      earlier S(D) segment to be progressively higher the later it occurred in the
      course of the FI 500 sec. This trend was shown roughly to parallel the increasing
      rate of responding in a conventional FI 500 sec with no interruption by S(Delta).
      Since the changing tendency to respond through the FI survives massive disruption
      by S(Delta), it is concluded that the control of responding through the FI does
      not require continuous mediating behavior. It is suggested that it is the
      decaying retroactive influence of the reinforcer on responses that occurred
      longer and longer before the reinforcer occurred which produces the familiar
      scalloped pattern of responding under FI schedules.

PMID- 16811285
TI  - Behavioral control by an imprinted stimulus.
AB  - Newly hatched ducklings were exposed to imprinting procedures and subsequently
      trained to peck a key by presenting the imprinting stimulus as the reinforcing
      (response contingent) event. It was found that the key peck was learned only when
      imprinting procedures were initiated during the first 6 to 8 hr after hatch.
      Additional studies revealed that: (1) the duckling's distress vocalizations were
      reduced in the presence of the imprinting stimulus and enhanced in its absence;
      (2) when the ducklings had constant access to the imprinted stimulus (via a key
      peck), pecking responses occurred in bursts and relatively few distress
      vocalizations occurred; (3) the initial effect of extinction procedures was an
      increase in key peck rate. When, however, repeated key pecks failed to produce
      the imprinted stimulus, distress vocalization ensued and peck rate declined; (4)
      both the presentation of an unfamiliar mechanical figure and delivery of
      electrical shock enhanced distress vocalization and key pecks; (5) for some
      ducklings, certain familiar objects in the environment influenced distress calls
      in a manner comparable to the imprinted stimulus in that distress calls increased
      when these objects were removed.

PMID- 16811286
TI  - Extinction-induced aggression.
AB  - Pigeons were conditioned to peck a response key under a procedure that alternated
      periods of food reinforcement with periods of extinction. The pigeons attacked a
      nearby pigeon at the onset of extinction. Some also attacked a stuffed model of a
      pigeon. The duration of attack was an inverse function of the time since the last
      food reinforcement and a direct function of the number of reinforcements. The
      pigeons attacked after the last food delivery whether or not the conditioned
      pecking response was required and whether or not the extinction period was
      signaled. The food had to be eaten; the mere sight and sound of food being
      delivered did not produce attack. Prior satiation reduced attack. The phenomenon
      was not attributable to a past history of competition between pigeons since
      socially deprived pigeons also attacked. Superstitious reinforcement of attack
      was not found to be a factor. The results indicated that the transition from food
      reinforcement to extinction was an aversive event that produced aggression.

PMID- 16811287
TI  - What is the experimental analysis of behavior?

PMID- 16811288
TI  - Discrimination learning as a function of stimulus location along an auditory
      intensity continuum.
AB  - Eight groups of rats were trained on an auditory intensity discrimination in
      which the discriminative stimuli were separated by 10 decibels (db). Four pairs
      of stimuli were selected from different regions along a 60-100 db (SPL) intensity
      continuum. Counterpart groups were trained on each stimulus pair, with the
      relative intensity positions of the reinforced stimulus (S(D)) and the non
      reinforced stimulus (S(Delta)) reversed for the two groups. Discrimination
      acquisition curves were compared to determine whether stimuli separated by equal
      logarithmic units were of comparable "difficulty", and to determine the relative
      effectiveness of an S(D) serving as the more versus less intense member of a
      stimulus pair. It was concluded that: (1) When S(D) is the more intense, auditory
      intensities of constant logarithmic separation are graded in "difficulty" along
      the intensity continuum; high intensity discriminative stimuli are most readily
      discriminated. When S(Delta) is the more intense, this graded effect is not
      evident. (2) For a given continuum location, discrimination is inferior when
      S(Delta) is the more intense. This effect is most pronounced at the high
      intensity end of the continuum and is chiefly attributable to differences in the
      rate of S(Delta) responding.

PMID- 16811289
TI  - Concurrent fixed-ratio and avoidance responding in the squirrel monkey.
AB  - Squirrel monkeys maintained concurrent performances appropriate to a fixed-ratio
      schedule of food reinforcement on one lever and an avoidance schedule on a second
      lever. The overall rate of responding maintained by either schedule was not
      systematically affected when the other schedule was discontinued and its lever
      removed.

PMID- 16811291
TI  - A suggestion concerning the anesthetization of the rat.

PMID- 16811290
TI  - An automatic method for the study of aggression in squirrel monkeys.

PMID- 16811292
TI  - Automatic stimulus attenuator for rapid discrimination training.

PMID- 16811293
TI  - Recovery of responses during mild punishment.
AB  - Pigeons were punished with mild shock for pecking during one of two components of
      a multiple schedule. They eventually recovered so that they pecked at the same
      rate during both components. In one experiment they were extinguished after
      recovering. When punishment was maintained during extinction, they extinguished
      faster during the punished, than during the unpunished component. When punishment
      was stopped during extinction, they extinguished faster during the unpunished
      than during the previously punished component. In another experiment, punishment
      was programmed first during neither of the two components, then during one, then
      during both, and finally during the other component. The extent of recovery
      decreased with each successive cycle. It is concluded that, if transient
      emotional states are ignored, reward and punishment are symmetrical in their
      effects.

PMID- 16811294
TI  - An electromechanical drinkometer.

PMID- 16811295
TI  - A sensitive electronic drinkometer.

PMID- 16811296
TI  - Schedules using noxious stimuli. I. Multiple fixed-ratio and fixed-interval
      termination of schedule complexes.
AB  - The termination of a schedule complex, comprising a stimulus in the presence of
      which brief presentations of electric shocks are scheduled, is a reinforcer.
      Conditions were studied under which schedule-controlled patterns of responding
      characteristic of fixed-interval, fixed-ratio, and multiple fixed-interval fixed
      ratio schedules can be maintained in the squirrel monkey by terminating a
      schedule complex. The schedule of shock presentation was a critical determinant
      of the patterns of responding, especially under fixed-interval schedules of
      termination. The rates and patterns of responding under various schedules of
      termination of schedule complexes were generally akin to those maintained under
      comparable schedules of food presentation. The findings suggest a general
      similarity in the dynamic aspects of performances under schedules of schedule
      complex termination and comparable schedules of food presentation. The schedule
      of reinforcement is more important than the nature of the reinforcer in the
      control of behavior.

PMID- 16811297
TI  - Microminiature connectors used as permanent electrode holders in the rat.

PMID- 16811298
TI  - Discriminative and reinforcing properties of two types of food pellets.
AB  - In Experiment I some discriminative functions of food pellets were studied by
      developing a multiple schedule of reinforcement (mult FR 30 FI 3) in which the
      delivery of a standard laboratory food pellet as a reinforcer set the occasion
      for reinforcement on every 30th response (FR 30), and the delivery of a sucrose
      food pellet as a reinforcer set the occasion for reinforcement after a 3-min
      interval (FI 3). Discriminative stimulus control by the type of pellet was also
      demonstrated by reversing the operant discrimination and having the standard
      pellet control the FI 3 and the sucrose pellet control the FR 30. In Experiment
      II a mult FR 30 FR 30 with two bars was developed; a standard food pellet was
      followed by an FR 30 on Bar 1 and extinction (ext) on Bar 2, while a sucrose
      pellet was followed by an FR 30 on Bar 2 and ext on Bar 1. A control rat was
      placed, for comparison, on a mixed (mix) FR 30 FR 30 schedule with two bars, but
      neither bar correlated with the type of food pellet. In Experiments I and II the
      similarity between pellet controlled multiple schedules and multiple primed
      schedules was discussed, as was the comparability of transitions and
      effectiveness of control between pellet controlled multiple schedules and
      multiple schedules providing continuous exteroceptive stimuli.

PMID- 16811299
TI  - Schedules using noxious stimuli. II: low intensity electric shock as a
      discriminative stimulus.
AB  - The presence or absence of pulses of low intensity electric shock was used as a
      discriminative stimulus to control responding under fixed ratio reinforcement in
      the squirrel monkey. Initially brief periods of nonreinforcement were lengthened
      only when discriminative control was evident. Discriminative control was studied
      by (1) varying the duration of nonreinforcement periods; (2) reversing the
      stimulus conditions correlated with reinforcement and nonreinforcement periods;
      and (3) determining the minimum shock intensity necessary to maintain
      discriminative control. Stimulus control was not reliably affected by d
      amphetamine, chlorpromazine, or morphine. The discriminative control by pulses of
      low intensity electric shock was similar to that by other discriminative stimuli,
      except that the control developed slowly and was better when the pulsing shock
      was correlated with reinforcement than when correlated with nonreinforcement.

PMID- 16811300
TI  - Operant reinforcement of an autonomic response: two studies.
AB  - Two successive studies were conducted to determine the possibility of operant
      reinforcement of nonspecific galvanic skin resistance responses. In the first
      study, with five experimental and three control subjects who served for 20 to 30
      min a day for 10 days, all experimental subjects learned to emit more nonspecific
      galvanic skin resistance responses than their ad hoc matched controls. In a
      second study, nine experimental and nine control subjects were matched for first
      day levels of reactivity and yoked for operant reinforcement schedules.
      Significant differences between the two groups were found on the last day of
      conditioning and during extinction. Six of the nine experimental subjects showed
      higher cumulative rate curves than their matched and yoked controls. The
      concomitant measures (basal resistance, heart rate, etc.) all supported this
      finding. It was suggested that operant reinforcement of autonomic response tends
      to maintain a certain level of responding in contrast to persistent adaptation in
      the control group.

PMID- 16811301
TI  - The course of acquisition of a line-tilt discrimination by rhesus monkeys.
AB  - Each of four groups of monkeys were trained on a different simultaneous
      discrimination procedure involving a vertical line as the correct choice. Each
      group, after acquiring the discrimination, was tested for generalization along
      the dimension of line tilt. Monkeys that learned to select the vertical line when
      the alternative choices were distinguished from the correct choice by two aspects
      (brightness and absence of line) showed almost complete tilt generalization (flat
      gradient). Monkeys that learned to select the line when the alternatives were
      distinguished only by the absence of the line showed poor tilt discrimination
      (generalization gradient slightly peaked at vertical). Monkeys developed a good
      tilt discrimination when nonvertical lines were gradually introduced by
      progressively darkening them on the previously blank alternatives. Monkeys
      developed a tilt discrimination with the lowest error rate when only horizontal
      alternatives were gradually introduced and then pairs of alternatives
      progressively closer to vertical were made available.

PMID- 16811302
TI  - The effectiveness of fading in programming a simultaneous form discrimination for
      retarded children.
AB  - A non-verbal teaching program, combined with reinforcement and extinction
      (Program Group), was compared with reinforcement and extinction alone (Test
      Group) in teaching retarded children to discriminate circles from ellipses. In
      the Program Group, fading techniques were used to transfer stimulus control from
      "bright vs. dark" to "form vs. no-form" and then to "circle vs. ellipse". The
      Test Group had the task of learning the circle-ellipse discrimination with no
      prior teaching program. With the program, seven of 10 children learned the circle
      ellipse discrimination. Without the program, one of nine learned. The eight Test
      Group children who failed to learn circle vs. ellipse were then given the
      opportunity to learn the form no-form discrimination by reinforcement and
      extinction alone, without fading. Six of the eight learned, but only three of
      these six then learned circle vs. ellipse on a second test. All seven Program
      Group children who had learned form vs. no-form also learned the circle-ellipse
      discrimination by means of fading; each of the seven made fewer errors than any
      of the three who succeeded on the second test. Children who failed to learn
      circle vs. ellipse adopted response patterns incompatible with the development of
      appropriate stimulus control.

PMID- 16811303
TI  - Preference for mixed- versus fixed-ratio schedules.
AB  - Pigeons' pecks on one key produced a stimulus correlated with a mixed-ratio
      schedule of food reinforcement. Pecks on a second key produced a stimulus
      correlated with a fixed-ratio schedule. When the arithmetic mean of the mixed
      ratios equaled the fixed ratio, the former stimulus maintained a higher rate of
      pecking. When the fixed ratio was sufficiently smaller, preference shifted to it.
      The pigeons' relative preference for the schedules could be described by
      comparing the geometric mean of the reinforcement rates in the several mixed
      ratio components with the reinforcement rates in the fixed-ratio components.

PMID- 16811304
TI  - Quasi-reinforcement: control of responding by a percentage-reinforcement
      schedule.
AB  - When a variable-interval schedule of reinforcement was segmented into small fixed
      interval components, with reinforcements following some components and brief
      blackouts following the others, rate of responding doubled and a positively
      accelerated pattern within each component was obtained. Presented according to
      this percentage reinforcement paradigm, the blackouts approximated the functions
      of a food reinforcer. These effects occurred only when the behavior sequence
      required to produce reinforcement was identical to that required to produce
      blackout. The quasi-reinforcing effects of these blackout stimuli suggest that a
      neutral stimulus need not occasion or accompany a primary reinforcer to acquire
      reinforcing properties.

PMID- 16811305
TI  - A new principle of pellet feeder design.

PMID- 16811306
TI  - Reinforcement of least-frequent sequences of choices.
AB  - When a pigeon's choices between two keys are probabilistically reinforced, as in
      discrete trial probability learning procedures and in concurrent variable
      interval schedules, the bird tends to maximize, or to choose the alternative with
      the higher probability of reinforcement. In concurrent variable-interval
      schedules, steady-state matching, which is an approximate equality between the
      relative frequency of a response and the relative frequency of reinforcement of
      that response, has previously been obtained only as a consequence of maximizing.
      In the present experiment, maximizing was impossible. A choice of one of two keys
      was reinforced only if it formed, together with the three preceding choices, the
      sequence of four successive choices that had occurred least often. This sequence
      was determined by a Bernoulli-trials process with parameter p. Each of three
      pigeons matched when p was (1/2) or (1/4). Therefore, steady-state matching by
      individual birds is not always a consequence of maximizing. Choice probability
      varied between successive reinforcements, and sequential statistics revealed
      dependencies which were adequately described by a Bernoulli-trials process with p
      depending on the time since the preceding reinforcement.

PMID- 16811307
TI  - Choice and delay of reinforcement.
AB  - Pigeons were trained to peck either of two response keys for food reinforcement
      on equated aperiodic schedules. The distribution of responding at the two keys
      was studied as reinforcement was delayed for various durations. The relative
      frequency of responding at each key was shown to match the relative immediacy of
      reinforcement, immediacy defined as the reciprocal of the delay of reinforcement.

PMID- 16811309
TI  - A tail electrode for unrestrained rats.

PMID- 16811308
TI  - Oscillatory behavior during approach-avoidance conflict.
AB  - During one stimulus, food rewards and electric shocks were intermittently
      delivered to rats regardless of their behavior. Subjects could either terminate
      or initiate this stimulus by pressing a lever. Effects of the relative frequency
      of food and shock were studied by manipulating the variable-interval schedules
      associated with each. Increases in the relative frequency of shocks led to
      decreases in the amount of time each rat spent in the stimulus. Subjects
      initiated and terminated the stimulus most often at intermediate relative
      frequencies of food and shock, rather than in situations where the conditions
      were either very favorable (e.g., only food was possible) or very unfavorable
      (e.g., only shock was possible). This technique thus provides quantitative data
      on oscillatory behavior during conflict which confirm and extend results
      previously obtained by qualitative observation.

PMID- 16811310
TI  - The effect of shock intensity on concurrent and single-key responding in
      concurrent-chain schedules.
AB  - Pigeons were trained to respond in a two-link, concurrent-chain schedule. Pecks
      on each key during the concurrent initial links occasionally produced a 5-min
      terminal link, during which only that key was operative. Food reinforcement and
      various intensities of shock were scheduled during the terminal links. When shock
      was contingent on response, the effect of shock was greater on terminal-link
      responding than on initial-link responding. When shock was independent of
      response, the effect was reversed, with larger changes in initial-link responding
      than terminal-link responding. In general, shock was found to affect behavior
      most drastically when behavior could, in turn, affect the rate of shock.

PMID- 16811311
TI  - The effects of punishment intensity on squirrel monkeys.
AB  - Responses of squirrel monkeys were maintained by a variable-interval schedule of
      food reinforcement. Concurrently, punishment consisting of a brief electric shock
      followed each response. As has been found for pigeons and rats, punishment did
      not produce extreme, all-or-none reactions. By gradually increasing the
      punishment intensity it was possible to produce response rates intermediate to no
      suppression and complete suppression. Similarly, the moment-to-moment response
      rate was free of extreme fluctuations. A "warm-up" effect occurred in which the
      punished responses were especially suppressed during the initial part of a
      session. The pre-punishment performance was negatively accelerated within a
      session, and punishment reduced the degree of negative acceleration. When
      punishment was discontinued, responding recovered immediately except when
      suppression had been complete or prolonged. When the punishment intensity was
      decreased gradually, more suppression resulted at a given intensity than when
      intensity was increased gradually. This suggests a "behavioral inertia" effect
      wherein behavior at a new punishment intensity is biased toward the behavior at
      the previous value. A corollary generalization is that the larger the change in
      intensity, the less the behavior at the new value will be biased toward the
      behavior at the previous value.

PMID- 16811312
TI  - The repeated acquisition of behavioral chains.
AB  - Monkeys were trained with food reinforcement in a chamber containing four groups
      of three levers. For each session the monkey's task was to learn a new four
      response chain by pressing the correct lever in each group. A stable pattern of
      learning resulted, and the number of errors reached a steady state from session
      to session. The technique was then used to determine how various durations of
      timeouts, following errors, affected the acquisition of new chains. With no
      timeout, the monkeys made a great many errors, due in large part to superstitious
      responses within the reinforced chain. Timeout durations ranging from 1 sec to 4
      min reduced the number of errors substantially. A second experiment investigated
      the effects upon acquisition errors of presenting a single light (an
      "instruction" stimulus) over the correct lever. When this light did not influence
      the monkeys' responses to the three alternatives, the chains were learned as
      without it. When the light did control responding, the monkey pressed the
      appropriate sequence of levers but did not learn the sequence. Thus, when the
      light was removed, the monkey performed as if learning that sequence for the
      first time.

PMID- 16811313
TI  - Separating the effects of interreinforcement time and number of
      interreinforcement responses.
AB  - The relative importance of interreinforcement time and interreinforcement
      responses was evaluated by varying each independently. To do this, a blackout was
      presented after each nonreinforced response under both fixed-ratio and fixed
      interval schedules of reinforcement. Manipulating the blackout duration under the
      fixed-ratio schedule caused interreinforcement time to vary without affecting the
      number of interreinforcement responses. Pigeons' post-reinforcement and post
      blackout response latencies were found to increase linearly with
      interreinforcement time. Under the fixed-interval schedule, the same blackout
      manipulations changed the number of interreinforcement responses without
      affecting interreinforcement time. Post-reinforcement and post-blackout response
      latencies under this condition were approximately constant. These results suggest
      that responding is controlled by interreinforcement time and is not influenced by
      the number of responses emitted between reinforcements.

PMID- 16811314
TI  - Spaced responding and choice: a preliminary analysis.
AB  - Pigeons were exposed to reinforcement both for short (2 < IRT < 3 sec) and long
      (10 < IRT < 11 sec) interresponse times. They developed bimodal interresponse
      time distributions, which were decomposable into two independent component
      distributions under the control of the short and long contingencies respectively.
      The birds' allocation of responses between these two distributions was determined
      by a simple power-law relationship between reinforcement ratios, and response
      ratios derived from the component distributions. Comparison between this
      situation and concurrent choice situations raises the possibility that the power
      law relation between ratios may be a more general law of choice than the matching
      of relative frequencies (probabilities).

PMID- 16811315
TI  - Some effects of relative reinforcement rate and changeover delay in response
      independent concurrent schedules of reinforcement.
AB  - Reinforcements were arranged independently of the pigeon's behavior by concurrent
      variable-interval schedules. The reinforcements arranged by one of the schedules
      occurred when the chamber was illuminated with amber light, and the
      reinforcements arranged by the other schedule occurred when the chamber was
      illuminated with blue light. Both schedules functioned concurrently, but
      reinforcers were delivered by each only in the presence of the appropriate
      stimulus condition. A response on a white key, the only key in the chamber,
      alternated the stimulus condition and the effective schedule. The results of this
      procedure were similar to those obtained with concurrent response-dependent
      variable-interval schedules of reinforcement. The proportion of the total session
      time spent in the presence of a schedule component approximated the proportion of
      the total number of reinforcements in the component. Changeover rate was a
      decreasing function of the changeover delay and of the difference between the
      relative rates of reinforcement for each pair of concurrent schedules.

PMID- 16811316
TI  - Some factors controlling preference between fixed-ratio and variable-ratio
      schedules of reinforcement.
AB  - A multiple schedule of food reinforcement for key-pecking was arranged which
      consisted of nine fixed-ratios, each of which operated in the presence of a
      different stimulus. Pigeons could complete a given fixed-ratio within the
      multiple schedule or, by pecking a second key, could switch from the fixed-ratio
      schedule to a variable-ratio schedule consisting of the same nine ratios. Stable
      switching behavior was established which did not maximize simple probability or
      rate of reinforcement. Instead, the subjects showed a stable preference for the
      variable-ratio schedule of food reinforcement. Increasing the number of responses
      required to switch, and removing the occasions on which reinforcement was
      delivered after a single response in the variable schedule, decreased the number
      of switches to the variable schedule. Periods of delay interposed between a
      completed switch and the availability of reinforcement after one response in the
      variable schedule also decreased switching to the variable schedule, particularly
      at long delay intervals.

PMID- 16811317
TI  - The dissociation of discriminative and conditioned reinforcing functions of
      stimuli with changes in deprivation.
AB  - Pigeons were studied in two experiments designed to explore the effects of
      deprivation level upon responding in each link of a two-link chained schedule.
      The stimulus associated with the terminal link of the chain can be both a
      discriminative stimulus (S(D)) for responding in the presence of the stimulus and
      a conditioned reinforcer (S(r)) for responding in the preceding link. Previous
      findings have indicated that the S(r) function was more readily weakened by
      satiation than was the S(D) function, i.e., the rate of responding decreased more
      rapidly in the initial link of the chain than in the terminal link. The first of
      the present experiments, in which tests were conducted after a series of
      sessions, produced different results: rates of responding in the two links
      declined simultaneously. The second experiment supported the hypothesis that the
      effects of satiation interact with the duration of maintenance on the satiation
      procedure: in early sessions the S(r) function was more readily disrupted, but in
      later sessions the rates of responding in the two links declined simultaneously.
      Subsequent to this extensive series of identical sessions, the pigeons'
      deprivation level was altered before a session by pre-feeding the pigeons up to
      their normal post-session weights. The rates of responding failed to reflect
      fully this change in deprivation in the first such session, suggesting that the
      pigeons' behavior had become partially independent of deprivation level.

PMID- 16811318
TI  - Stimulus bias in the absence of food reinforcement.
AB  - Pigeons sometimes peck a key at different rates in the presence of different
      stimuli, even when the same schedule of reinforcement is correlated with each of
      these stimuli. The possibility that the occurrence of such stimulus bias is
      dependent on adventitious effects of food reinforcement in the presence of the
      stimuli was evaluated by correlating extinction with two stimuli. Both pigeons
      showed stimulus bias, indicating that the occurrence of this phenomenon is not
      critically dependent upon any effects of scheduled food reinforcements.

PMID- 16811319
TI  - Differential reinforcement and stimulus control of not responding.
AB  - Pigeons were trained to respond with equal variable-interval reinforcement in the
      presence of a white key and also a white key with a vertical line. They were then
      trained not to respond to the vertical line by extinguishing the response or by
      reinforcing its non-occurrence at various frequencies. During training, the rate
      of key-pecking in the presence of the white key, maintained by a constant
      variable-interval schedule of reinforcement, depended on the frequency of
      reinforcement in the presence of the line. When lines of different orientations
      were presented in a generalization test, birds trained with extinction responded
      more to other orientations than to the vertical line, whereas those trained with
      high frequencies of reinforcement for not responding tended to respond equally at
      all line orientations. Intermediate frequencies of reinforcement gave mixed
      results.

PMID- 16811320
TI  - Discrimination learning, the peak shift, and behavioral contrast.
AB  - A discrimination between two successively alternating stimuli was trained under
      conditions that maintained equal frequencies of reinforcement in the presence of
      each of the discriminative stimuli (S1 and S2) but that also reduced the rate of
      responding to S2. These conditions included a multiple variable-interval
      differential-reinforcement-of-low-rate schedule and a multiple variable-interval
      variable-interval schedule in which responses to S2 were punished. Whenever the
      rate of responding to S2 was reduced, rate of responding to S1 (behavioral
      contrast) increased, and the peak of a subsequently obtained generalization
      gradient did not occur at the expected location (between S1 and S2) but was
      displaced away from S2, below S1. Discrimination training in which the
      frequencies of reinforcement earned in S1 and S2 were not equal (variable
      interval 1-min variable-interval 5-min training) produced contrast and the peak
      shift only if the rate of responding to S2 had been reduced, as after non
      differential reinforcement in which variable-interval 1-min schedules were
      correlated with S1 and with S2. It was concluded that a sufficient condition for
      the occurrence of behavioral contrast and the peak shift was reduction of the
      rate of responding to one of two alternating discriminative stimuli and that a
      peak shift will occur only if contrast had occurred during discrimination
      training.

PMID- 16811321
TI  - Generalization gradients of inhibition after different amounts of training.
AB  - Five groups of pigeons received seven sessions of variable-interval reinforcement
      for pecking a blank white key, followed by either 1, 2, 4, 8, or 16 sessions of
      training on a successive discrimination in which the positive stimulus was the
      blank white key and the negative stimulus was a black vertical line on the white
      key. After training, a generalization test was administered along the line-tilt
      continuum. Relative gradients of inhibition became steeper with increased amounts
      of training, and reliably nonhorizontal absolute gradients were obtained only
      from groups of subjects with at least four days of training. Therefore,
      inhibitory stimulus control improves with added training. Several problems with
      the concept of "inhibition" are examined and some implications of the results for
      theoretical analyses of operant discrimination learning are discussed.

PMID- 16811322
TI  - Indifference between punishment and free shock: evidence for the negative law of
      effect.
AB  - Pigeons were trained to respond under two conditions with two identical variable
      interval schedules of positive reinforcement. While the schedules operated for
      separate response keys, they were not available concurrently. During one
      condition, each response was punished with electric shock. During the other
      condition, shocks were delivered independently of responding. The punishment
      suppressed responding but the free shocks did not. However, when allowed to
      choose, the pigeons preferred the condition associated with the lowest rate of
      shock regardless of whether or not the shock was dependent on responding. In
      general, shocks exerted their greatest effect on whichever response had the
      greatest influence on shocks. In this respect, punishment is instrumental in
      suppressing behavior and the properties of punishment are symmetrical to those of
      reinforcement. This empirical symmetry dictates a corresponding conceptual
      symmetry in terms of a positive law of effect accounting for response increments
      and a negative law accounting for response decrements.

PMID- 16811323
TI  - A restraining device for implanting shock delivery electrodes in birds.

PMID- 16811324
TI  - Punishment: the interactive effects of delay and intensity of shock.
AB  - A discrete-trial punishment procedure, with rats, was used to examine how delay
      of-shock intervals of 0 to 28 sec and shock intensity interact to decrease the
      frequency and increase the latency of a positively reinforced response. For delay
      of-shock intervals of 0, 7, 14, and 28 sec, there was a range of shock
      intensities, for some subjects, over which the punishing effect of shock was an
      increasing, monotonic function of shock intensity. For other subjects this
      transition was abrupt. Functions relating response frequency and latency measures
      to shock intensity were displaced toward higher values on the shock intensity
      axis with an increase in delay-of-shock interval. The effects of "gradual" and
      "abrupt" introduction to "severe" shock, as well as re-exposure to previously
      used shock intensities, were examined under both the immediate and delay-of-shock
      conditions. With delay-of-shock intervals of 7, 14, or 28 sec, shock intensities
      of approximately 0.50 milliamperes or greater were necessary to decrease
      substantially the number and increase the latency of the lever-pressing response.
      For the immediate punishment group this intensity was approximately 0.20 ma.
      These facts were related to Annau and Kamin's (1961) conditioned emotional
      response experiment in which a shock intensity of 0.49 ma or greater was required
      to suppress the rate of a positively reinforced response.

PMID- 16811325
TI  - An automated variable-force operandum.

PMID- 16811326
TI  - Fixed-interval punishment.
AB  - The average rate of bar-pressing maintained by a variable-interval schedule of
      milk reinforcement in 33 rats was found to be a decreasing function of intensity
      of concurrent punishment and, over a wide range of shock intensities, was
      inversely related to punishment frequency. Cumulative records were, however,
      negatively accelerated during 30-min punishment sessions with complete
      suppression occurring earlier and earlier (after fewer and fewer shocks) as
      intensity increased. In addition, acceleration was often observed between
      successive fixed-interval shock presentations and, at low and moderate
      intensities, bursts of responding occurred after each shock. The time to recover
      between punishment sessions (post-punishment recovery) was an increasing
      monotonic function of punishment intensity.

PMID- 16811327
TI  - The effect of response force on avoidance rate.
AB  - In a Sidman-avoidance schedule of counter losses for two human subjects, the loss
      to-loss and response-to-loss intervals were 20 sec. The avoidance response was a
      vocal response that was louder than a minimum vocal requirement. This requirement
      was set at 80 db, 95 db, or 110 db. In addition to vocal responses meeting the
      minimum requirement, all responses exceeding a threshold of 75 db or louder were
      recorded. The rate of both above-threshold and avoidance responses decreased as
      the response-force requirement increased. Thus, high response-force requirements
      produced an effect on avoidance responding similar to its effect on positively
      reinforced responding.

PMID- 16811329
TI  - Responding in the cat maintained under response-independent electric shock and
      response-produced electric shock.
AB  - Key-pressing responses in the cat were maintained under conditions in which brief
      electric shock was first postponed by responses (avoidance), then periodically
      presented independently of responses, and finally produced by responses on a
      fixed-interval schedule of 15 min (FI 15-min). A steady rate of responding
      occurred under shock avoidance and under response-independent shock; positively
      accelerated responding was engendered by the FI 15-min schedule. A second
      experiment studied responding under second-order schedules composed of three FI 5
      min components. Responding was suppressed when a stimulus was presented briefly
      at completion of each FI 5-min component and a shock followed the brief stimulus
      at completion of the third component. Responding was maintained when each of the
      first two components was completed either with or without presentation of a brief
      stimulus and a shock alone was presented at completion of the third FI 5-min
      component.

PMID- 16811328
TI  - Schedules using noxious stimuli. III. Responding maintained with response
      produced electric shocks.
AB  - Responding was maintained in two squirrel monkeys under several variations of a
      10-min fixed-interval schedule of electric shock presentation. The monkeys were
      first trained under a 2-min variable-interval schedule of food presentation, and
      then under a concurrent schedule of food presentation and shock presentation. In
      one monkey, when shocks (12.6 ma) followed each response during the last minute
      of an 11-min cycle ending with a timeout period, responding was increased during
      the first 10 min and suppressed during the last minute of each cycle. When the
      shock schedule was eliminated, both the enhancement and suppression disappeared,
      and a steady rate of responding was maintained under the variable-interval
      schedule. When the food schedule was eliminated, the shock schedule maintained a
      characteristic fixed-interval pattern of responding during the first 10 min, but
      suppressed responding during the last minute of each cycle. The fixed-interval
      pattern of responding was maintained when the timeout period was eliminated and
      when only one shock could occur at the end of the cycle. In the second monkey,
      responding under the concurrent food and shock schedule was suppressed when
      responses produced shocks after 3-min. Under an 11-min cycle, responding
      continued to be maintained at increasing shock intensities. When the food
      schedule was eliminated, a fixed-interval pattern of responding was maintained
      under a 10-min schedule of shock presentation (12.6 ma). Whether response
      produced electric shocks suppressed responding or maintained responding depended
      on the schedule of shock presentation.

PMID- 16811330
TI  - Stimulus generalization as a function of the delay between training and testing
      procedures: a reevaluation.
AB  - Three groups of 12 pigeons each were trained to discriminate between lights of
      550 mmu (S(D)), correlated with 1-min variable-interval reinforcement and 570 mmu
      (S(Delta)), correlated with extinction. Group A was tested for wavelength
      generalization in extinction 1 min after meeting the discrimination criterion;
      Group B was tested 24 hr later; Group C was tested 24 hr later after a 3-min
      (reinforced) warm-up with the S(D). The post-discrimination gradient of Group B
      was significantly flatter and showed significantly greater area shift than that
      of Groups A and C. The gradient of Group C was similar to that of Group A,
      indicating that the warm-up eliminated the effect of the delay period.

PMID- 16811331
TI  - Response rate as a function of amount of reinforcement for a signalled concurrent
      response.
AB  - Pigeons were exposed to two equal, concurrent variable-interval schedules of
      reinforcement on two response keys. One key was continuously illuminated. Pecking
      on that key produced reinforcements of constant duration. The other key was
      normally dark, except that availability of reinforcement was signalled by
      illuminating the key. The duration of access to a grain reinforcer was varied on
      the key that signalled reinforcement. Rate of response on the first key, the one
      that did not signal reinforcement, was found to vary inversely with duration of
      signalled reinforcement on the other key. The latency between the signal and the
      peck that produced signalled reinforcement remained about constant. These results
      show that responding on one key in concurrent variable-interval schedules depends
      on the reinforcement delivered by both schedules and is independent of responding
      on the other key.

PMID- 16811332
TI  - Conditional discrimination learning in the pigeon.
AB  - Four pigeons received conditional discrimination training in which reinforcement
      contingencies were related to specific combinations of color and form, but were
      unrelated to either color or form considered separately. During discrete-trial
      training, each response in the presence of two of four color-form displays
      produced reinforcement and terminated the trial; responding to the other two
      displays was never reinforced, and each such response prolonged the particular
      trial on which it occurred. Subsequently, the subjects received multiple-schedule
      training in which responding to either of the displays previously associated with
      reinforcement was now reinforced on a variable-interval schedule, and extinction
      was the schedule again correlated with the other two displays. After differential
      responding to the stimuli was clearly evident, intensity of the combination
      displays was changed in subsequent training sessions. Complex stimulus control
      was generally maintained across variation in intensity, although there were
      temporary disruptions in performance associated with onset of some of the
      intensity changes. Finally, a component-stimulus test revealed considerably more
      responding to the forms than to the colors.

PMID- 16811333
TI  - Extinction of a heterogeneous chain after several reinforcement schedules.
AB  - Rats were conditioned to emit the following two-member chain of responses on two
      different operanda always available: responses on a vertical bar produced a
      discriminative stimulus for food-reinforced responding on a horizontal bar.
      Responses on the vertical bar produced a discriminative stimulus on a variable
      interval 1-min schedule, and the horizontal bar produced food on a variable ratio
      of 10 responses. Control conditions were included in which vertical bar responses
      were also food-reinforced simultaneous with the onset of the discriminative
      stimulus for the horizontal bar response and a tandem schedule which had the same
      response requirements but without different exteroceptive stimuli associated with
      the separate components of the response chain. The latter condition greatly
      retarded acquisition of the response chain compared to the other schedules
      studied here and compared to reports in the literature on homogeneous (single
      operandum) response chains. Intermittent reinforcement of the chain led to
      greater resistance to extinction of both members and the chain remained intact
      longer in the sense that stimulus control was maintained.

PMID- 16811334
TI  - Intermittent punishment of human responding maintained by intermittent
      reinforcement.
AB  - To determine the effects of variable-interval shock punishment on behavior
      maintained by variable-interval and variable-ratio reinforcement, human subjects'
      key-pressing behavior was reinforced with money on a four-component multiple
      schedule. Components 1 and 2 were variable-interval 30-sec, and Components 3 and
      4 were variable-ratio 210. After responding was stabilized, response-contingent
      electric shock was scheduled on a variable-interval 10-sec schedule during the
      second and fourth components of each cycle. Subjects instructed as to the
      reinforcement contingencies showed gradually increasing suppression of variable
      interval responding at increasing shock intensities and either very high or very
      low rates of variable-ratio responding at higher intensities. Minimally
      instructed subjects showed suppression at higher shock intensities, but no clear
      differential suppression as a function of reinforcement schedule. Recovery from
      initial suppression was observed within sessions.

PMID- 16811335
TI  - Continuous punishment of free-operant avoidance in the rat.
AB  - Three groups of albino rats were trained under a free-operant avoidance (Sidman)
      procedure with equal shock-shock and response-shock intervals. After stable
      performance was achieved, the animals were concurrently exposed to a brief
      electric shock after each response. The procedures were as follows: Punishment
      Schedule I: punishment shock was introduced at an intensity approximately one
      quarter that of avoidance shock; increments of nearly this same size were made as
      stable performance was achieved at succeeding punishment shock intensities.
      Punishment Schedule II: punishment shock was introduced at approximately one-half
      the intensity of avoidance shock; after stable performance, punishment shock was
      increased to the same intensity as avoidance shock. Punishment Schedule III:
      punishment shock was introduced and maintained at the same intensity as avoidance
      shock. Punishment was continued for all groups until one of two suppression
      criteria was attained. All animals made fewer responses and received more
      avoidance shocks as a function of increasing punishment shock. Half of the
      animals under Punishment Schedule I required punishment shock higher than
      avoidance shock to meet their assigned suppression criterion. A comparison of all
      procedures showed that suppression was greater when punishment shock was
      initially at high intensity.

PMID- 16811336
TI  - Periodic shock with added clock.
AB  - Rats were shocked every 6 min while responding was maintained on a variable
      interval schedule of reinforcement. With some rats, shocks were interspersed with
      a sequence of three different stimulus conditions (S3-->S2-->S1), or clock cues,
      each lasting 2 min. For other rats, a single stimulus condition prevailed between
      shocks at the beginning of the experiment and clock cues were introduced later.
      Response rate decreased from S3 to S1. Response rate in S3, S2, and S1 was
      inversely related to shock intensity. When clock cues were added, response rate
      increased in all 2-min intershock periods. During clock cues, an index of
      curvature, indicating the degree of negative acceleration of response rate, was
      greatest for S1 and least for S3, and was directly related to shock intensity.
      The response-facilitating effect of shock and its relation to a possible
      discriminative function of shock and to behavioral contrast is discussed.

PMID- 16811337
TI  - Positive conditioned suppression: conditioned suppression using positive
      reinforcers as the unconditioned stimuli.
AB  - Research has revealed the phenomenon of conditioned suppression in which the rate
      of responding is reduced during a stimulus that is paired with noncontingent
      shock. The present study replicated this procedure, but used noncontingent
      positive reinforcers instead of the aversive shock. The lever-pressing responses
      of rats were reinforced with food or water. While the rats were responding, a
      stimulus was occasionally presented and paired with the delivery of a
      noncontingent positive reinforcer, which was either food, water, or brain
      stimulation for different rats. The result was a reduction in the rate of
      responding during the conditioned stimulus. This finding shows that conditioned
      suppression occurs during a signal for reinforcing as well as aversive stimuli.

PMID- 16811338
TI  - A response-spacing effect: an absence of responding during response-feedback
      stimuli.
AB  - In most studies of operant reinforcement a response-feedback stimulus is used
      which is so brief that the nature of the responding during it is virtually
      undetectable. The present study investigated the nature of this responding by
      lengthening an initially brief feedback stimulus. The key-pecking responses of
      pigeons were maintained by a variable-interval schedule of food reinforcement.
      Each response produced a brief stimulus light in addition to the usual auditory
      response feedback. When the duration of the feedback stimulus light was gradually
      increased, it was found to control a nearly zero rate of responding. The result
      was a paced, metronomic-like performance in which the pigeon made a single
      response, paused until the stimulus terminated, and then responded again. As a
      result, the overall response rate was greatly reduced; the mean interresponse
      time approximated the stimulus duration. A plausible interpretation is that brief
      feedback stimuli acquire control over responding because they coincide with few
      responses and few reinforcers. These findings show that in addition to their
      known functions as conditioned-reinforcing stimuli and discriminative stimuli,
      response-feedback stimuli also exert direct stimulus control: responding is
      reduced during the feedback stimulus itself.

PMID- 16811339
TI  - A two-relay flip-flop.

PMID- 16811340
TI  - Measurement of consummatory behavior in the fish.

PMID- 16811341
TI  - Variability of response location for pigeons responding under continuous
      reinforcement, intermittent reinforcement, and extinction.
AB  - The effect of several reinforcement schedules on the variability in topography of
      a pigeon's key-peck response was determined. The measure of topography was the
      location of a key peck within a 10-in. wide by 0.75-in. high response key. Food
      reinforcement was presented from a magazine located below the center of the
      response key. Variability in response locus decreased to a low value during
      training in which each response produced reinforcement. Variability increased
      when fixed intervals, variable intervals, random intervals, or extinction were
      scheduled.

PMID- 16811342
TI  - Analysis of response rates during stimulus generalization.
AB  - In the presence of one click frequency, the presses of two hungry rats on one of
      two levers were reinforced with food on variable-interval schedules; in the
      presence of a different click frequency, presses on the other lever were
      reinforced. In stimulus generalization tests, a variety of click frequencies were
      presented and reinforcement withheld. The test stimuli were found to exert
      control over which of the two levers the rats pressed, but not over the rate of
      pressing the selected lever. The results were interpreted as further evidence
      that intermediate rates in generalization gradients may be the result of the
      alternation of several distinct behavior patterns.

PMID- 16811343
TI  - Generalization gradient shape and summation in steady-state tests.
AB  - Pigeons' pecks at one or two wavelengths were reinforced intermittently. Random
      series of adjacent wavelengths appeared without reinforcement. Gradients of
      responding around the reinforced wavelengths were allowed to stabilize over a
      number of sessions. The single (one reinforced stimulus) and summation (two
      reinforced stimuli) gradients were consistent with a statistical decision account
      of the generalization process.

PMID- 16811344
TI  - Studies on responding under fixed-interval schedules of reinforcement: the
      effects on the pattern of responding of changes in requirements at reinforcement.
AB  - In pigeons responding under a 180-sec fixed-interval schedule of reinforcement,
      the frequency distribution of the duration of the final interresponse time before
      the reinforcer was compared with the distribution of the preceding two
      interresponse times. The results confirmed qualitatively and quantitatively the
      expected preferential reinforcement of longer interreinforcement times under
      fixed-interval reinforcement. Requirements at reinforcement were then changed to
      eliminate the preferential reinforcement of longer interresponse times. Local
      patterns and mean rate of responding could change, without the characteristic
      fixed-interval pattern of increasing responding through the interval (scalloping)
      being much affected. It is concluded that this characteristic pattern of fixed
      interval responding does not depend crucially on effects of the reinforcer at the
      moment of reinforcement, but rather to effects extending over much longer periods
      of time than just the last interresponse time.

PMID- 16811345
TI  - The bisection of a brightness interval by pigeons.
AB  - Pigeons were trained on a discrete trials, successive discrimination procedure,
      in which the stimuli were two luminance values on the center key. Behavior was
      maintained by 25% reinforcement of correct responses on two side-keys. During
      occasional test trials the luminance of the center key was maintained at one of a
      number of values, intermediate to those of the two training stimuli, and a
      function relating the relative frequency of responses on the two side keys to
      stimulus intensity was obtained. The intersection of this function with the 50%
      line provided an estimate of the bisection point. Since no bisection point
      occurred below the geometric mean of the interval, the results were not
      consistent with a logarithmic scale of brightness but fitted the general mean
      theorem with an exponent of 0.24. With continued testing, the performance of
      individual subjects oscillated in an irregular manner about the mean bisection
      point. The relative stability of the test behavior and the absence of context
      effects indicated that the method was suitable as a general procedure for
      measuring stimulus distances.

PMID- 16811346
TI  - Focus difference in cue fading: a new technique.

PMID- 16811347
TI  - Factors influencing inhibitory stimulus control: discrimination training and
      prior non-differential reinforcement.
AB  - In Exp. I, shallow U-shaped gradients of inhibition in the line-orientation
      dimension were obtained from birds that had a vertical (0 degrees ) line on a
      green surround correlated with extinction and a blank green surround correlated
      with reinforcement. Birds that had massed extinction in the presence of the 0
      degrees line showed flat gradients. Thus, discrimination training, but not massed
      extinction, appears to generate inhibitory control. In Exp. II, as in studies of
      control by a stimulus correlated with punishment, non-differential training
      across the line-orientation dimension preceded further sessions. Steep inverted
      gradients about the 0 degrees line were obtained after discrimination training
      with the 0 degrees line correlated with extinction. Gradients obtained after
      massed extinction tended to be flat. Again, discrimination training was critical
      in obtaining negative gradients of stimulus control.

PMID- 16811348
TI  - Behavioral contrast in one component of a multiple schedule as a function of the
      reinforcement conditions operating in the following component.
AB  - The key pecks of four pigeons were reinforced on a variable-interval 5-min
      schedule which operated in each of the four components of a multiple schedule,
      indicated by red, green, yellow, and blue stimuli and presented in such an order
      that the red stimulus always preceded the yellow and the green stimulus always
      preceded the blue. After establishing baseline rates, the reinforcement schedule
      associated with the blue and yellow components was altered so that one was now an
      extinction schedule and the other was a variable-interval 1-min schedule. In a
      second experimental stage, the blue stimulus was interchanged with the yellow so
      that the red stimulus preceded the blue and the green stimulus preceded the
      yellow. In both experimental stages the response rate in the variable-interval 5
      min component that preceded the extinction component was higher than the response
      rate in the variable-interval 5-min component that preceded the variable-interval
      1-min component. The results were discussed in relation to the importance of
      stimulus ordering in experiments concerned with investigating behavioral
      contrast.

PMID- 16811349
TI  - Preference for mixed-interval versus fixed-interval schedules.
AB  - Pigeons were trained on a two-link concurrent chain schedule in which responses
      on two keys were reinforced according to independent variable-interval schedules
      by the production of a change in key color. Further responses on the key on which
      the stimulus change had been produced gave a single food reinforcement and a
      return to concurrent variable-interval conditions. On one key the terminal link
      was a two-valued mixed-interval schedule, while on the other, the terminal link
      was a fixed-interval schedule. When the mixed-interval values were kept constant
      and the fixed-interval values varied, relative response rates in the initial
      concurrent links matched relative reinforcement rates in the terminal links when
      these were computed from cubic transformations of the reciprocals of the
      intervals comprising the terminal link schedules.

PMID- 16811350
TI  - Effects of reinforcement magnitude on pigeons' preference for different fixed
      ratio schedules of reinforcement.
AB  - In concurrent, two-member chains, the completion of one or the other of two
      initial percentage fixed-interval 90-sec links produced a terminal link in which
      the completion of a fixed ratio produced food reinforcement. The fixed ratios and
      the duration of reinforcement in the terminal links were varied. Relative
      response rate in initial links was proportional to the relative reinforcement
      duration per ratio response (reinforcement duration divided by fixed ratio) in
      terminal links. The rate of responding in the terminal fixed-ratio links was
      insensitive to both ratio size and reinforcement duration and therefore did not
      vary sufficiently to distinguish between responses per reinforcement and
      immediacy of reinforcement as controlling variables in terminal links.

PMID- 16811351
TI  - Concurrent schedules of primary and conditioned reinforcement in rats.
AB  - Rats responded on a fixed-interval schedule during which a 3-sec stimulus
      preceded each water reinforcement. The stimulus was then scheduled concurrently
      for responses on the same lever according to either a variable ratio. Although
      water reinforcement continued on a fixed-interval schedule, the pattern of
      responding became typical of a variable-interval or variable-ratio schedule. When
      the 3-sec stimulus was presented on a variable-interval or variable-ratio
      schedule, but was omitted on the fixed-interval schedule, the response rate
      decreased. When the stimulus occurred after the same time periods as those of the
      variable-interval schedule, but at least 7-sec after the last response, the rate
      decreased. The rate became higher when the fixed-interval schedule was
      discontinued and each presentation of the 3-sec stimulus was followed by water on
      a variable-interval schedule. When both water and the 3-sec stimulus were
      discontinued for a period of time, resulting in extinction of the lever response,
      and the 3-sec stimulus alone then presented on a variable-interval or variable
      ratio schedule after lever responses, rate increased and then gradually
      decreased.

PMID- 16811352
TI  - Contiguity of briefly presented stimuli with food reinforcement.
AB  - Pigeons performed on second-order schedules of reinforcement consisting of four
      fixed-interval components. Only the terminal component ended with food.
      Performance was studied both when a brief stimulus followed the completion of
      each of the first three fixed intervals (brief-stimulus schedule) and when the
      stimulus was omitted (tandem schedule). Variations in the temporal contiguity of
      the last presentation of the stimulus and the presentation of food indicated that
      the shorter the delay, the greater was the enhancement of rate of responding in
      comparison with tandem performance. A positively accelerated pattern of
      responding within fixed-interval components was a function of the contiguity of
      the brief stimulus and reinforcement; this pattern was absent for all tandem
      schedule performance.

PMID- 16811353
TI  - Auto-shaping in bobwhite quail.
AB  - Bobwhite quail were given extended auto-shaping, a procedure in which response
      key illumination or color change is paired with response-independent food
      presentations. Continuation of the auto-shaping procedure yielded increased
      responding across sessions, although responses were never instrumental in
      producing food. The quail were shifted directly from the auto-shaping procedure
      to a variable-interval 60-sec schedule of reinforcement. All three birds were
      approaching stable response rates by the fifth session on the variable-interval
      schedule.

PMID- 16811354
TI  - Effects of timeout on spaced responding in pigeons.
AB  - Three pigeons were trained under a differential-reinforcement-of-low-rate
      schedule of 20 sec, and then exposed to a schedule under which responses
      terminating interresponse times less than 20 sec produced timeout and responses
      terminating interresponse times greater than 20 sec produced reinforcement.
      Response-produced timeouts selectively decreased the probability of short
      interresponse times and thereby produced a higher frequency of reinforcement. The
      suppressive effect of timeout was independent of timeout duration, with timeouts
      of 5, 10, or 20 sec. Similar effects were found when the minimum interresponse
      time that could be terminated by response-produced reinforcement was increased to
      30 sec. The suppressive effects of timeout on responding maintained by these
      schedules were similar to previous reports in which responding was punished with
      electric shock.

PMID- 16811355
TI  - A system for the recording and analysis of interresponse-time data using an AM
      tape recorder and digital computers.

PMID- 16811356
TI  - Compounding of pre-aversive stimuli.
AB  - When two discriminative stimuli, each capable of maintaining a response, are
      combined, their compound will maintain a frequency of response greater than the
      frequencies maintained by the individual stimuli. This has been called additive
      summation. The present experiments extended the investigation of this phenomenon
      to a converse situation in which two pre-aversive stimuli were combined. Each pre
      aversive stimulus was capable of reducing the frequency of an ongoing response.
      The combination of these stimuli reduced the relative frequency of response below
      that resulting from either stimulus. Furthermore, the compounding of two highly
      suppressive stimuli produced more suppression than the compounding of two less
      suppressive stimuli. Evidence was also presented to suggest that the compound
      continued to reduce responding even when the single stimuli were no longer
      effective. A fourth experiment demonstrated that summation of response tendencies
      could not be accounted for in terms of stimulus intensity or sensory interaction.

PMID- 16811357
TI  - Fixed-interval schedules of electric shock presentation: extinction and recovery
      of performance under different shock intensities and fixed-interval durations.
AB  - In squirrel monkeys responding under a schedule in which responding postponed the
      delivery of electric shock, the presentation of response-dependent shock under a
      fixed-interval (FI) schedule increased the rate of responding. When the schedule
      of shock-postponement was eliminated, so that the only shocks delivered were
      those produced by responses under the FI schedule, a pattern of positively
      accelerated responding developed and was maintained over an extended period. When
      responses did not produce shocks (extinction), responding decreased. When shocks
      were again presented under the FI schedule, the previous pattern of responding
      quickly redeveloped. In general, response rates were directly related to the
      intensity of the shock presented, and inversely related to the duration of the
      fixed-interval. These results raise fundamental questions about the traditional
      classification of stimuli as reinforcers or punishers. The basic similarities
      among FI schedules of food presentation, shock termination, and shock
      presentation strengthen the conclusion that the schedule under which an event is
      presented and the characteristics of the behavior at the time the event is
      presented, are of overriding importance in determining the effect of that event
      on behavior.

PMID- 16811358
TI  - J. R. Kantor's Objective Psychology of Grammar and Psychology and Logic: a
      retrospective appreciation.

PMID- 16811359
TI  - Controlling human fixed-interval performance.
AB  - Both high and relatively constant rates of responding without post-reinforcement
      pauses and lower rates with pauses after reinforcement are produced by human
      subjects under fixed-interval (FI) schedules. Such FI rates and patterns may be
      controlled when subjects are provided with different histories of conditioning
      and different conditions of response cost (reinforcement penalties per response).
      Subjects with a conditioning history under ratio schedules typically produce high
      and relatively constant rates of responding under FI schedules; this responding
      does not change systematically with changes in FI value. In contrast, subjects
      with a history under schedules which produce little or no responding between
      reforcements [such as differential-reinforcement-of-low-rate (DRL) schedules]
      tend to pause after reinforcement and respond at low rates under FI schedules,
      whether or not they also have ratio conditioning histories; cost increases the
      likelihood of this type of performance. For DRL-history subjects, post
      reinforcement pauses increase and response rates decrease as FI values increase.

PMID- 16811360
TI  - Delayed reinforcement versus reinforcement after a fixed interval.
AB  - When interreinforcement intervals were equated, pigeons demonstrated little or no
      preference between reinforcement after a delay interval and reinforcement
      presented on a fixed-interval schedule. The small preferences sometimes found for
      the fixed interval (a) were considerably smaller than when the delay and fixed
      intervals differed in duration, and (b) were caused by the absence of light
      during the delay. These results suggest that the effects of delayed reinforcement
      on prior responding can be reproduced by imposing a temporally equal fixed
      interval schedule in place of the delay; and, therefore, that the time between a
      response and reinforcement controls the probability of that response, whether
      other responses intervene or not.

PMID- 16811361
TI  - Successive interresponse times in fixed-ratio and second-order fixed-ratio
      performance.
AB  - Three rats were trained on a schedule in which every sixth response produced a
      timeout of 5 sec minimum duration, and food was delivered at the onset of
      timeout. Successive interresponse times were measured under these conditions, and
      also when behavior was maintained by second-order fixed-ratio and fixed-interval
      schedules. Under the second-order schedules, each six-response fixed-ratio
      component was followed by a timeout, and occasionally food was delivered at the
      onset of a timeout. In the fixed-ratio schedule, the successive interresponse
      times showed a decrease followed by an increase before food delivery, but this
      systematic variation in interresponse times was not found when the performance
      was under second-order reinforcement. Under both second-order schedules the
      latencies of successive components, and the successive interresponse times within
      each component, showed a decrease as food delivery was approached.

PMID- 16811362
TI  - Reinforcement frequency and contingency as factors in fixed-ratio behavior.
AB  - Two variables often confounded in fixed-ratio schedules are reinforcement
      frequency and response requirement. These variables were isolated by a technique
      that yoked the distributions of reinforcements in time for one group of pigeons
      to those of pigeons responding on various fixed-ratio schedules. The
      contingencies for the yoked birds were then manipulated by adding various tandem
      fixed-ratio requirements to their schedules. Post-reinforcement pause was
      approximately equal for the yoked and ratio pigeons, and was relatively
      insensitive to changes in the tandem requirement. Terminal response rate
      increased with increases in the tandem requirement, even though reinforcement
      rate was invariant. This increase was attributed to the progressive interference
      of the tandem requirement with the differential reinforcement of long
      interresponse times.

PMID- 16811363
TI  - Notes on fixed-ratio and fixed-interval escape responding in the pigeon.
AB  - After learning to peck a key when each peck removed a slowly increasing series of
      electric shocks, pigeons were placed on fixed-ratio and fixed-interval escape
      schedules. The resulting behavior was comparable to that of other species on
      ratio and interval escape schedules. Thus, while the pigeon apparently requires
      special techniques for the initial shaping of a key-peck response with negative
      reinforcement, this response, once obtained, can be subjected to intermittent
      schedules of negative reinforcement with no great difficulty.

PMID- 16811364
TI  - The concurrent reinforcement of two interresponse times: the relative frequency
      of an interresponse time equals its relative harmonic length.
AB  - The relative lengths of two concurrently reinforced interresponse times were
      varied in an experiment in which three pigeons obtained food by pecking on a
      single key. Visual discriminative stimuli accompanied the two time intervals in
      which reinforcements were scheduled according to a one-minute variable-interval.
      The steady-state relative frequency of an interresponse time approximately
      equalled the complement of its relative length, that is, its relative harmonic
      length. Thus, lengths of interresponse times and delays of reinforcement have the
      same effect on the relative frequencies of interresponse times and choices in one
      key and two-key concurrent variable-interval schedules, respectively. A second
      experiment generalized further the functional equivalence between the effects of
      these one-key and two-key concurrent schedules by revealing that the usual
      matching-to-relative-immediacy in two-key concurrent schedules is undisturbed if
      reinforcement depends upon the occurrence of a response at the end of the delay
      interval, as it does in the one-key schedules. The results of both experiments
      are consistent with a quantitative theory of concurrent operant behavior.

PMID- 16811365
TI  - Reinforcement contingencies maintaining collateral responding under a DRL
      schedule.
AB  - Two-key conjunctive schedules were studied with one key (food key) under a
      differential-reinforcement-of-low-rate 20-sec schedule, while the consequences of
      responding on another key (collateral key) were varied. When food depended not
      only upon a food-key interresponse time in excess of 20 sec, but also upon the
      occurrence of one or more collateral-key responses during the food-key
      interresponse time, the rate of collateral-key responding was low and food-key
      interresponse times rarely exceeded 20 sec. When collateral-key responses could
      produce a discriminative stimulus correlated with the availability of food under
      the DRL schedule, the discriminative stimulus functioned as a conditioned
      reinforcer to maintain higher rates of collateral-key responding, and the spacing
      of food-key responses increased. If the occurrence of the discriminative stimulus
      was independent of collateral-key responses, the rate of collateral-key
      responding was again low, but the spacing of food-key responses was still
      controlled by the discriminative stimulus. Both the conditioned reinforcer and
      the explicit reinforcement contingency could maintain collateral-key responding,
      but the adventitious correlation between collateral-key responses and the
      delivery of food could not maintain very much collateral-key responding. The
      pattern of responding on the food-key was determined to a much greater extent by
      the correlation between the discriminative stimulus and the delivery of food than
      by the pattern of responding on the collateral key.

PMID- 16811366
TI  - Control of responding by the elements of a compound discriminative stimulus and
      by the elements as individual discriminative stimuli.
AB  - In the first of two studies, the responding of four albino rats was
      differentially reinforced in the presence of noise and light together and then
      tested in the presence of the noise and the light separately during extinction.
      The light exercised substantially more control of responding than did the noise.
      In the second study the responding of a similar group of four rats was
      differentially reinforced in the presence of the noise and the light separately.
      Control of responding by the light developed more rapidly than control by the
      noise. Results suggest that levels of control by stimuli after differential
      reinforcement with respect to the stimuli together can be predicted by the rates
      of development of control during differential reinforcement with respect to the
      stimuli separately.

PMID- 16811367
TI  - Some determinants of inhibitory stimulus control.
AB  - Interspersed reinforcement and extinction during discrimination learning generate
      a U-shaped gradient of inhibition about the stimulus correlated with extinction.
      The present work showed that extinction is not a necessary determinant of
      inhibitory stimulus control. In Exp. I, a reduction in the rate of reinforcement,
      through a shift from a multiple variable-interval 1-min variable-interval 1-min
      schedule to a multiple variable-interval 1-min variable-interval 5-min schedule,
      resulted in a post-discrimination line orientation gradient of inhibition about
      the stimulus correlated with the variable-interval 5-min schedule. In Exp. II,
      the rates of reinforcement, correlated with a pair of stimuli, were held constant
      during a shift from a multiple variable-interval 1-min variable-interval 1-min
      schedule to a multiple variable-interval 1-min differential-reinforcement-of-low
      rate schedule. Inhibitory stimulus control about the stimulus correlated with the
      differential reinforcement of low rate was obtained. In both experiments, a
      reduction in the rate of responding during one stimulus and behavioral contrast
      during the other stimulus preceded the observation of inhibitory stimulus
      control.

PMID- 16811368
TI  - Repeated measurements of reinforcement effects on gradients of stimulus control.
AB  - Two experiments studied the effects of reinforcement schedules on generalization
      gradients. In Exp. 1, after pigeons' responding to a vertical line was
      reinforced, the pigeons were tested with 10 lines differing in orientation.
      Reconditioning and the redetermination of generalization gradients were repeated
      from 8 to 11 times with the schedule of reinforcement varied in the
      reconditioning phase. Stable gradients could not be observed because the
      successive reconditionings and tests steepened the gradients and reduced
      responding. Experiment 2 over-came these effects by first training the birds to
      respond to all of the stimuli. Then, brief periods of reinforced responding to
      the stimulus correlated with reinforcement alternated with the presentation of
      the 10 lines in extinction. The development of stimulus control was studied eight
      times with each bird, twice with each of four schedules of reinforcement.
      Gradients were similar each time a schedule was imposed; the degree of control by
      the stimulus correlated with reinforcement varied with particular schedules.
      Behavioral contrast occurred when periods of reinforcement and extinction
      alternated and was more durable with fixed-interval, variable-interval, and
      variable-ratio schedules than with fixed-ratio or differential-reinforcement-of
      low-rate schedules.

PMID- 16811369
TI  - Generalization during acquisition, extinction, and transfer of matching with an
      adjustable comparison.
AB  - Three groups of pigeons were given conditional discrimination training in which
      the number of standard stimuli was varied across groups. In the presence of each
      standard, a pigeon adjusted the comparison stimulus on a second key until the two
      keys matched. A report of this match (response on the first key) was reinforced.
      Transfer of the matching performance was investigated by adding new standards to
      the ones already available. All pigeons were exposed to two extinction sessions
      after 155 sessions of training. Rapidity of acquisition was inversely related to
      the number of standards presented. Generalization gradients derived from the
      several comparison stimuli showed that all pigeons reached a high level of
      accuracy in the presence of at least one standard, and some pigeons did so in the
      presence of as many as four of the six standards. There was no evidence of a
      systematic effect of extinction upon overall accuracy, or the individual
      generalization gradients. When a new standard was added, a given pigeon's
      performance (in terms of responding to the comparisons) was similar to
      performance in the presence of one of the old standards. However, the pigeons did
      not show evidence of confusion among the comparisons.

PMID- 16811370
TI  - Auto-maintenance in the pigeon: sustained pecking despite contingent non
      reinforcement.
AB  - If a response key is regularly illuminated for several seconds before food is
      presented, pigeons will peck it after a moderate number of pairings; this "auto
      shaping" procedure of Brown and Jenkins (1968) was explored further in the
      present series of four experiments. The first showed that pecking was maintained
      even when pecks turned off the key and prevented reinforcement (auto
      maintenance); the second controlled for possible effects of generalization and
      stimulus change. Two other experiments explored procedures that manipulated the
      tendency to peck the negatively correlated key by introducing alternative
      response keys which had no scheduled consequences. The results indicate that
      pecking can be established and maintained by certain stimulus-reinforcer
      relationships, independent of explicit or adventitious contingencies between
      response and reinforcer.

PMID- 16811371
TI  - Autoshaping of key pecking in pigeons with negative reinforcement.
AB  - Pigeons exposed to gradually increasing intensities of pulsing electric shock
      pecked a key and thereby reduced the intensity of shock to zero for 2 min.
      Acquisition of key pecking was brought about through an autoshaping process in
      which periodic brief keylight presentations immediately preceded automatic
      reduction of the shock. On the occasions of such automatic reduction of shock
      preceding the first measured key peck, little or no orientation to the key was
      observed. Observations of pigeons with autoshaping of positive reinforcement also
      revealed little evidence of orientation toward the key.

PMID- 16811372
TI  - Escape and avoidance of shock by pigeons pecking a key.
AB  - Pigeons had been trained to peck a key when each peck removed a slowly increasing
      series of electric shocks. Without loss of the established key-pecking response,
      the birds were gradually weaned from this procedure to one where intense shocks
      were presented suddenly, duplicating features that had proved ineffective for
      initial shaping of the response. Finally, a procedure was introduced in which key
      pecks could avoid shock. Avoidance responding was maintained in two of three
      pigeons.

PMID- 16811373
TI  - Selective attention: the effects of combining stimuli which control incompatible
      behavior.
AB  - Four rhesus monkeys learned both a color and tilt discrimination. The stimuli
      were combined to produce incompatible behavior. The behavior controlled by one
      set of stimuli was reinforced until "errors" virtually disappeared. The stimuli
      were tested separately again. Sixteen replications of the entire procedure
      indicated that the stimuli producing "errors" were ignored.

PMID- 16811375
TI  - An automated pneumatic shutter release for time-lapse photography.

PMID- 16811374
TI  - Probability of reinforcement and the development of stimulus control.
AB  - Pigeons were trained with a successive discrimination procedure in which
      responding during the negative stimulus was never reinforced and responding
      during the positive stimulus was reinforced according to one of four probability
      values. This discrimination training followed extensive training with a single,
      neutral stimulus and the same temporal distribution of reinforcements. The
      development of stimulus control was studied by tracing the difference in rate of
      responding between the positive and negative stimuli over the course of
      discrimination training. Response rate during the positive stimulus remained
      constant, while that during the negative stimulus decreased to zero. The
      probability of reinforcement associated with the positive stimulus affected both
      the total number of responses emitted during the negative stimulus and the number
      of negative stimulus presentations during which responding occurred. However, the
      number of reinforcements during the positive stimulus preceding the attainment of
      various degrees of stimulus control was similar for all probability values.

PMID- 16811376
TI  - Stimulus control and the response-reinforcement contingency.
AB  - Pigeons were trained under a schedule in which reinforcement was made available
      at varying periods of time after a prior reinforcement. The first key peck after
      a reinforcer was available began a timer and a second key peck, which exceeded a
      specified minimal time interval, produced the reinforcer. It was shown that a
      contingency which contains a minimal interresponse time does not necessarily
      weaken stimulus control by an exteroceptive stimulus.

PMID- 16811377
TI  - A source of artifact in in-line readout projectors.

PMID- 16811378
TI  - Stimulus control in the goldfish after massed extinction.
AB  - Compared with the data of goldfish trained only with stimuli correlated with
      reinforcement, interspersed reinforcement-stimulus and extinction-stimulus trials
      resulted in sharper stimulus control and a marked reduction in the percentage of
      key-presses emitted in the presence of stimuli located near the extinction
      stimulus on the test dimension. If non-reinforced trials were not interspersed
      with reinforced trials, there was no sharpening of stimulus control and less
      reduction in key presses in the presence of stimuli near the extinction stimulus
      on the test dimension.

PMID- 16811379
TI  - Extinction of a discriminative operant following discrimination learning with and
      without errors.
AB  - Different groups of pigeons were trained to respond to red and not to green with
      and without errors (responses to green) under a free operant procedure, in which
      responding to red was intermittently reinforced, and under a trial procedure in
      which all responses to red were reinforced. The response to red was then
      extinguished under a procedure in which the discriminative stimuli were
      successively alternated as during discrimination training. The performances of
      those birds that learned the discrimination without errors under the trial
      procedure were seriously disrupted during extinction; the birds persistently
      responded to green for the first time. The performances of those subjects that
      learned the discrimination without errors under the free operant procedure were
      not disrupted during extinction. In a second experiment, the same discrimination
      was trained without errors under a trial procedure in which the response to red
      was intermittently reinforced. Extinction did not disrupt discrimination
      performance. Thus, errorless discrimination performance was shown to remain
      intact during extinction so long as the response to red was intermittently
      reinforced during discrimination training.

PMID- 16811380
TI  - Multiple fixed-interval schedules: transient contrast and temporal inhibition.
AB  - Pigeons were exposed to four cycles per session of a multiple schedule in which
      each cycle involved twelve 60-sec fixed intervals followed by four 180-sec
      intervals [(12 FI 60-sec)(4 FI 180-sec) schedule]. Post-reinforcement pauses were
      shorter during the first few short intervals of each cycle than during later
      short intervals, and increased over the four long intervals of each cycle
      (positive and negative transient contrast). A (12 FI 15-sec)(4 FI 45-sec)
      schedule showed similar results. These two schedules differed in some other
      respects indicating effects of absolute FI duration on stimulus control.
      Differences in contrast properties between both these procedures and multiple
      variable-interval schedules were related to the pause-producing property of
      reinforcement on FI (temporal inhibition). Behavior under two other multiple
      fixed-interval schedules-(2 FI 360-sec)(1 FI 720-sec) and (3 FI 360-sec)(1 FI 720
      sec)-differed in certain respects from both the (12 FI x-sec)(4 FI 3x-sec)
      schedules. These differences may be related to differences in the number of
      successive fixed intervals within a component (run length).

PMID- 16811381
TI  - Concurrent fixed-ratio fixed-interval performances in adult human subjects.
AB  - Two undergraduate males worked for money on a button-pressing task associated
      with concurrent fixed-ratio fixed-interval schedules of reinforcement.
      Manipulations of the fixed-ratio requirement produced an interaction between the
      various fixed-ratio and fixed-interval performances. When the fixed ratio was
      small, more fixed-interval responding occurred per interval than when the fixed
      ratio was large. In general, the data were similar to those obtained with lower
      organisms except that no post-reinforcement pause or ratio strain was seen.

PMID- 16811382
TI  - The effect of reinforcement magnitude upon responding under fixed-ratio
      schedules.
AB  - Responding under fixed-ratio schedules was studied as a function of two durations
      of food presentation. Latency of the first response after food presentation (post
      reinforcement pause) was consistently shorter when food was presented for the
      longer duration. Only one of the four pigeons studied showed a consistently
      higher response rate, exclusive of post-reinforcement pause, as a function of the
      longer access to food. When ratio size was reduced, pause durations decreased,
      and the differences related to the two durations of food presentations became
      progressively smaller.

PMID- 16811383
TI  - Discrete-trial alternation in the rat.
AB  - The acquisition and maintenance by rats of single alternation, double
      alternation, and four other repeating patterns of reinforced and non-reinforced
      trials was studied in a discrete-trial lever-pressing situation. The rats learned
      all these patterns in a small number of experimental sessions. Single alternation
      was learned more rapidly than the more complex patterns. Rate of learning single
      and double alternation decreased moderately as inter-trial interval increased.
      Abrupt changes in the scheduling of trials, either by doubling the inter-trial
      interval or by shifting from fixed to variable trial spacing, temporarily
      disrupted the patterned performance. Two hypotheses concerned with the means by
      which the rats could have learned to conform to the pattern were examined: (1)
      "timing" of the interval between successive reinforcements; and (2) control of
      responding on a trial by the outcome of preceding trials, depending on the
      consistency with which these outcomes were associated with reinforced or non
      reinforced trials in the pattern and on how many trials back these outcomes
      occurred. The second hypothesis accounted for the relative frequency of errors on
      trials at various locations in the sequences, and predicted most of the changes
      in error frequency observed in experiments in which "inter-trial stimuli" were
      added to the sequences.

PMID- 16811384
TI  - A pulse former triggered by current interruption.

PMID- 16811385
TI  - Conditioned suppression under positive, negative, and no contingency between
      conditioned and unconditioned stimuli.
AB  - Using a conditioned suppression procedure, the effects of three contingent
      relationships between conditioned (CS) and unconditioned (US) stimuli were
      investigated. A traditional positive (if CS-then US) contingency suppressed
      response rate during the CS relative to responding during stimulus-free minutes
      of the session. A negative (if CS-then no US) contingency resulted in suppressed
      responding during CS-off minutes, and rate increases during the CS. A no
      contingency control procedure, during which CS and US were randomly related,
      almost totally suppressed responding throughout the session and showed no
      differential effects of the CS on response rate. An analysis of changes in
      response rate during the minute after US-offset revealed acceleration under the
      no-contingency condition and, to a somewhat lesser degree, under the negative
      contingency. Both conditioned suppression and non-suppression are analyzed in
      terms of the temporal relationship between CS and US.

PMID- 16811386
TI  - Two temporal parameters of free operant discriminated avoidance in the rhesus
      monkey.
AB  - Four monkeys were exposed to free operant discriminated avoidance (discriminated
      Sidman avoidance) in a parametric study of safe stimulus and warning stimulus
      duration. The safe stimulus was assigned values of 2, 5, 10, 20, and 40 sec, the
      warning stimulus values of 2, 5, and 20 sec. Rate of responding was a decreasing
      negatively accelerated function of safe stimulus duration, with a small effect
      attributable to warning stimulus duration. Control of response rate by safe
      stimulus duration was due to the predominance of responding in the presence of
      the warning stimulus. Responding during the safe stimulus was independent of the
      temporal parameters except at schedules combining short safe and short warning
      stimulus durations. Latencies of responses in the warning stimulus were analyzed,
      and mean latency was found to be a direct function of warning stimulus duration,
      with only one exception, resulting from the order in which the warning stimulus
      values were presented. Shock rate was not systematically related to either of the
      manipulated parameters.

PMID- 16811387
TI  - Shaping avoidance behavior in restrained monkeys.
AB  - Lever-pulling avoidance behavior of 24 monkeys was actively shaped with a manual
      shock-control box and a closed-circuit TV system. A negative reinforcement
      procedure was used wherein a periodically occurring body shock was postponed each
      time the subject moved toward the lever. All subjects were trainable with this
      method, two-thirds of them in fewer than five, 1- to 2-hr sessions. Negative
      reinforcement was more effective than a punishment procedure.

PMID- 16811388
TI  - The creative porpoise: training for novel behavior.
AB  - Two rough-toothed porpoises (Steno bredanensis) were individually trained to emit
      novel responses, which were not developed by shaping and which were not
      previously known to occur in the species, by reinforcing a different response to
      the same set of stimuli in each of a series of training sessions. A technique was
      developed for transcribing a complex series of behaviors on to a single
      cumulative record so that the training sessions of the second animal could be
      fully recorded. Cumulative records are presented for a session in which the
      criterion that only novel behaviors would be reinforced was abruptly met with
      four new types of responses, and for typical preceding and subsequent sessions.
      Some analogous techniques in the training of pigeons, horses, and humans are
      discussed.

PMID- 16811390
TI  - "Avoidance" in behavior theory.

PMID- 16811389
TI  - The rabbit as a subject in behavioral research.
AB  - Domestic rabbits were exposed to a wide variety of variables employed in
      behavioral research. It was found that: (1) Although food could be used as a
      reinforcer, the long periods of severe deprivation required to reduce body weight
      made its use impractical. (2) Water was an efficient reinforcer in that it
      maintained high rates of behavior after 22 hr of deprivation. (3) Except that
      rates of responding were higher, fixed-ratio and variable-interval schedules of
      reinforcement produced patterns of behavior similar to those demonstrated by rats
      and pigeons. (4) Although the duration of the post-reinforcement pause was a
      function of the duration of the interval under fixed-interval schedules,
      scalloping, as defined as a gradually increasing rate of responding between
      reinforcement, was not evident. (5) When provided with the means to both turn on
      and turn off intracranial stimulation, the duration of the stimulation and the
      frequency with which it was turned on and off was a function of the intensity of
      the stimulation. (6) Electric shock could suppress behavior and maintain escape
      responding, but would maintain avoidance responding only in a few subjects.

PMID- 16811391
TI  - The Davis platform.

PMID- 16811392
TI  - A two-state analysis of fixed-interval responding in the pigeon.
AB  - The behavior of pigeons on six geometrically spaced fixed-interval schedules
      ranging from 16 to 512 sec is described as a two-state process. In the first
      state, which begins immediately after reinforcement, response rate is low and
      constant. At some variable time after reinforcement there is an abrupt transition
      to a high and approximately constant rate. The point of rapid transition occurs,
      on the average, at about two-thirds of the way through the interval. Response
      rate in the second state is an increasing, negatively accelerated function of
      rate of reinforcement in the second state.

PMID- 16811393
TI  - Reinforcement omission on fixed-interval schedules.
AB  - EXPERIMENTS WITH PIGEONS AND RATS SHOWED THAT: (1) When a brief blackout was
      presented in lieu of reinforcement at the end of 25% of intervals on a fixed
      interval 2-min schedule, response rate was reliably and persistently higher
      during the following 2-min intervals (omission effect). This effect was largely
      due to a decrease in time to first response after reinforcement omission. (2)
      When blackout duration was varied, within sessions, over the range 2 to 32 sec,
      time to first response was inversely related to the duration of the preceding
      blackout, for pigeons, and for rats during the first few sessions after the
      transition from FI 2-min to FI 2-min with reinforcement omission. Post-blackout
      pause was independent of blackout duration for rats at asymptote. These results
      were interpreted in terms of differential depressive effects of reinforcement and
      blackout on subsequent responding.

PMID- 16811394
TI  - Effects of instructions and reinforcement-feedback on human operant behavior
      maintained by fixed-interval reinforcement.
AB  - In three experiments, human subjects were trained on a five-component multiple
      schedule with different fixed intervals of monetary reinforcement scheduled in
      the different components. Subjects uninstructed about the fixed-interval
      schedules manifested high and generally equivalent rates regardless of the
      particular component. By comparison, subjects given instructions about the
      schedules showed orderly progressions of rates and temporal patterning as a
      function of the interreinforcement intervals, particularly when feedback about
      reinforcement was delivered but also when reinforcement-feedback was withheld.
      Administration of the instructions-reinforcement combination to subjects who had
      already developed poorly differentiated behavior, however, did not make their
      behavior substantially better differentiated. When cost was imposed for
      responding, both instructed and uninstructed subjects showed low and
      differentiated rates regardless of their prior histories. It was concluded that
      instructions can have major influences on the establishment and maintenance of
      human operant behavior.

PMID- 16811395
TI  - Relations between patterns of responding and the presentation of stimuli under
      second-order schedules.
AB  - Key-pecking behavior in the pigeon was maintained under second-order schedules in
      which food was presented after a variable number of 2-min fixed-interval
      components were completed. When either the same stimulus (Exp. I) or different
      stimuli (Exp. II) appeared on the key during consecutive components, and a
      stimulus that was occasionally paired with food was presented briefly at
      completion of each component, (1) patterns of positively accelerated responding
      were maintained during the components, and, (2) mean response rates were
      generally as high during the initial components of a sequence as during the later
      components. In both experiments, when the food-paired stimulus was omitted and
      either no stimulus or a stimulus never paired with food was presented at
      completion of each component, mean rates of responding increased, but patterns of
      positively accelerated responding were not maintained during individual
      components. When a food-paired stimulus was not presented at completion of the
      components, mean response rates in Exp. I were low during the initial components
      of a sequence and gradually increased during subsequent components; in Exp. II
      mean response rates were variable, and pauses and abrupt changes in response
      rates were typical.

PMID- 16811396
TI  - Choice and rate of reinforcement.
AB  - Pigeons' responses in the presence of two concurrently available (initial-link)
      stimuli produced one of two different (terminal-link) stimuli. The rate of
      reinforcement in the presence of one terminal-link stimulus was three times that
      of the other. Three different pairs of identical but independent variable
      interval schedules controlled entry into the terminal links. When the
      intermediate pair was in effect, the pigeons distributed their (choice) responses
      in the presence of the concurrently available stimuli of the initial links in the
      same proportion as reinforcements were distributed in the mutually exclusive
      terminal links. This finding was consistent with those of earlier studies. When
      either the pair of larger or smaller variable-interval schedules was in effect,
      however, proportions of choice responses did not match proportions of
      reinforcements. In addition, matching was not obtained when entry into the
      terminal links was controlled by unequal variable-interval schedules. A
      formulation consistent with extant data states that choice behavior is dependent
      upon the amount of reduction in the expected time to primary reinforcement, as
      signified by entry into one terminal link, relative to the amount of reduction in
      expected time to reinforcement signified by entry into the other terminal link.

PMID- 16811398
TI  - A pole and leash handling system for primates.

PMID- 16811397
TI  - Concurrent performances: inhibition of one response by reinforcement of another.
AB  - In an analysis of interactions between concurrent performances, variable-interval
      reinforcement was scheduled, in various sequences, for both keys, for only one
      key, or for neither key of a two-key pigeon chamber. With changeover delays of
      0.5 or 1.0 sec, and with each key's reinforcements discriminated on the basis of
      key-correlated feeder stimuli, reinforcement of pecks on one key reduced the
      pecking maintained by reinforcement on the other key. The decrease in pecking
      early after reinforcement was discontinued on one key was not substantially
      affected by whether pecks on the other key were reinforced, but after
      reinforcement was discontinued on both keys, reinstatement of reinforcement for
      one key sometimes produced transient increases in pecking on the other key.
      Correlating the availability of right-key reinforcements with a stimulus, which
      maintained right-key reinforcement while reducing right-key pecking to negligible
      levels, demonstrated that these interactions depended on concurrent
      reinforcement, not concurrent responding. Thus, reinforcement of a response, but
      not necessarily the occurrence of the response, inhibits other reinforced
      responses. Compared with accounts in terms of excitatory effects of extinction,
      often invoked in treatments of behavioral contrast, this inhibitory account has
      the advantage of dealing only with observed dimensions of behavior.

PMID- 16811399
TI  - Reinforcement duration and the peak shift in post-discrimination gradients.
AB  - Pigeons were trained to key-peck for food, first with single-stimulus training
      and then with successive discrimination (multiple schedule) training. In the
      multiple schedule, two different wavelengths were each correlated with equally
      frequent variable-interval reinforcement but different durations (6 sec vs. 2
      sec) of access to grain. For some birds, the different durations of feeding cycle
      were cued by different intensities of the food hopper light. For some of these
      "cued" birds, single-stimulus training had been carried out with 6-sec feedings
      and when multiple-schedule training was introduced, the novel stimulus was
      correlated with 2-sec feedings. For the others, 2-sec feedings were originally
      used, and the novel stimulus was then present during the 6-sec reinforcement
      duration. The cueing procedure enhanced discrimination performance, and was
      necessary for the consistent production of a peak shift. In addition, the
      condition in which original training had been carried out with 6-sec feedings,
      and thus reinforcement duration was reduced in the presence of the novel
      stimulus, led to the best performance.

PMID- 16811400
TI  - Blocking the development of stimulus control when stimuli indicate periods of
      nonreinforcement.
AB  - To learn whether prior discrimination training based on one stimulus would block
      learning about a subsequently added stimulus, rats were first trained to press a
      bar on a variable-interval schedule of food reinforcement. Occasional stimuli
      were presented during which no reinforcement was available. Responding became
      suppressed in the presence of these stimuli. Stimuli could be noise, light, or a
      compound of noise plus light. A group trained with noise in Phase 1, then trained
      with the compound in Phase 2, showed less suppression to light in a subsequent
      test than a group that had the same compound training in Phase 2 but only
      variable-interval training in Phase 1. This showed that prior training with noise
      blocked the development of control by light during compound training. Two further
      groups showed that noise training following compound training did not have the
      same effect on control by light.

PMID- 16811401
TI  - Running-wheel activity and avoidance in the mongolian gerbil.
AB  - In the first of two experiments, running-wheel activity and unsignaled (Sidman)
      avoidance were studied in gerbils and albino rats. All gerbils ran at higher
      rates than any of the four rats studied. Under the avoidance procedure, four rats
      developed effective responding; the other two performed much less successfully.
      While avoidance developed more slowly in the gerbils, all showed asymptotic
      performance as effective as the four superior rats. The rats showed a consistent
      warm-up effect, receiving 60% to 80% of the total shocks in the initial third of
      the session. The gerbils displayed no warm-up, with shocks being evenly
      distributed over the session. Warm-up in the rats was not related to either
      response rate or to how effectively the animal was avoiding. When shock was
      removed, extinction occurred more rapidly in the rats than the gerbils. In the
      second experiment, which involved two-way shuttle avoidance, gerbils and albino
      mice quickly acquired the response. All animals met a criterion of 90% avoidance
      over 80 trials.

PMID- 16811402
TI  - Enhancement of off-key pecking by on-key punishment.
AB  - Under a variable-interval food reinforcement schedule, some of a pigeon's pecking
      responses land on the wall area adjacent to the response key. These off-key pecks
      increase in frequency when key responses produce shocks and decrease when shock
      is removed.

PMID- 16811403
TI  - Generalization of conditioned suppression after differential training.
AB  - In a modified conditioned suppression procedure, clicks at one frequency (danger
      signal) preceded shocks, while no shocks followed clicks at a different frequency
      (safe signal). During generalization tests, the maximal response rate was
      frequently shifted from the safe signal in the direction away from the danger
      signal, and the minimal response rate was frequently shifted in the opposite
      direction, away from the safe signal. There was considerable variability in the
      results from one animal to another. The generalization tests also suggested
      different generalization functions according to whether the danger signal was a
      lower or a higher frequency than the safe signal. The results also showed the
      development of systematic differences in response rate during and after the safe
      and danger signals, notably a relatively high rate at the beginning of the safe
      signal and after the danger signal.

PMID- 16811404
TI  - Conditioned suppression as a sensitive baseline for social facilitation.
AB  - The key pecking of pigeons maintained on a variable-interval schedule of food
      reinforcement was suppressed during occasional presentations of a warning
      stimulus paired with electric shock. On alternate sessions, a co-actor pigeon was
      visible in an adjoining chamber where it emitted the same food-reinforced key
      peck during the warning stimulus that signalled shock for the subject. With no
      shock and at low shock intensities, where the subject's responding was not
      suppressed or suppressed only slightly, the co-actor had little effect. At the
      higher shock intensities, where the subject's responding was reduced by at least
      40%, the response rate during the warning stimulus was consistently higher when
      the co-actor was present. One explanation of these results assumes a special
      relationship between social stimuli and aversive stimuli in which the presence of
      another animal reduces emotional reactions and thereby allows operant responses
      to increase. This was not the case here because the mere presence of the co-actor
      did not maintain social facilitation. Rather, the present results, taken in
      conjunction with previous findings, suggest that changes in social and non-social
      variables which affect the rate of food-reinforced responding may produce
      proportionately larger changes in responding when that responding is suppressed
      by aversive stimulation than when it is not.

PMID- 16811405
TI  - Attack behavior as a function of minimum inter-food interval.
AB  - Pigeons were exposed to a procedure in which food was presented after a fixed
      period of time had elapsed, provided no attack against a nearby stuffed pigeon
      had occurred during the last 15 sec of the period. As the minimum inter-food
      interval was increased logarithmically through seven values from 15 sec to 960
      sec, attack increased to a maximum and then decreased. For both pigeons, attack
      predominantly occurred after, rather than shortly before, food deliveries.

PMID- 16811406
TI  - A rat lever with remotely variable inertia.

PMID- 16811407
TI  - The effect of rate of delivery of response-independent shocks upon avoidance
      responding.
AB  - Two hooded rats were trained to bar-press to avoid electric shock on a continuous
      avoidance schedule with response-shock and shock-shock intervals equal. The rate
      of delivery of response-independent shocks superimposed on this schedule was
      varied. The response-independent shocks led to generally higher response rates
      but, with responses during shock omitted, the rates decreased as the response
      independent shock rate was increased. The actual shock rate received by the
      subjects was linearly related to the maximum potential shock rate. There was an
      increasing, negatively accelerated function between percentage avoidance and
      response rate, but there was no consistent relation between the number of shocks
      avoided and response rate. Response rate decreased as the potential shock rate
      increased, but responding was maintained even when as few as 15% of the shocks
      could be avoided.

PMID- 16811408
TI  - Density and delay of punishment of free-operant avoidance.
AB  - In two experiments, the free-operant shock-avoidance behavior of rats was
      punished by electric shock. Two aspects of the schedule of response-produced
      shock were varied: the frequency of punishment over time (punishment density) and
      the temporal interval between the punished response and the punishment
      (punishment delay). The general finding was that response-produced shock
      suppressed avoidance responding under most of the density-delay combinations
      studied, and suppression increased as a function of increases in density and
      decreases in delay. Rate increases of small magnitude also were observed, usually
      as an initial reaction to the lesser densities and longer delays. Response
      suppression, while decreasing the number of punishment shocks received, also
      increased the number of avoidance shocks, so that the total number of shocks
      received usually was greater than the minimal number possible. The results were
      discussed from the standpoint of similarities between the effects of punishing
      positively and negatively reinforced behavior. The finding that subjects did not
      minimize the total number of shocks suggested that when avoidance behavior is
      punished, responding is controlled more by the local consequences of responding
      than by overall shock frequencies during the course of the session.

PMID- 16811409
TI  - Conditioning history and the control of human avoidance and escape responding.
AB  - Inter-subject differences in response rates under free-operant avoidance and
      escape schedules are commonly obtained from humans. Data are presented which
      demonstrate that such differences can be controlled experimentally by giving
      subjects different conditioning histories. Subjects given a fixed-ratio history
      avoided and/or escaped from "point-loss periods" at higher rates than subjects
      given a differential-reinforcement-of-low-rates history. History related
      differences in response rates were maintained during 40 hr of escape responding.
      For low-rates history subjects, response rates under escape contingencies
      decreased as the rate of point-loss periods decreased.

PMID- 16811410
TI  - The effects of escape conditioning and shock intensity on responding during
      inescapable shock.
AB  - Eight albino rats, conditioned to press a lever to escape shock, continued to
      lever press during short inescapable shocks presented subsequently. The rate of
      this behavior was found to be higher for higher shock intensities regardless of
      the order in which shock values were presented. Relative to the immediately
      preceding escape rate, responding during inescapable shock was higher following
      conditioning at higher fixed-ratio escape requirements. Four subjects not
      conditioned to escape shock pressed the lever very infrequently during
      inescapable shock and showed little change with changes in shock intensity. The
      escape conditioning effects suggest that responding during inescapable shock is
      superstitious escape behavior. The effects of shock intensity on this behavior
      appear to be similar to reported effects of shock intensity on escape behavior.

PMID- 16811411
TI  - Persistent shock-elicited responding engendered by a negative-reinforcement
      procedure.
AB  - A procedure in which responses reduced intermittently presented electric shocks
      to one quarter of their originally scheduled intensity, effectively engendered
      and maintained lever pressing in hooded rats. This contingency also markedly
      increased the response rates of rats initially trained under an unsignaled
      avoidance procedure. The responding of all animals extinguished rapidly when
      shock was withdrawn. Subsequently, it was discovered that high response rates
      could be maintained solely through presentation of shocks that were not affected
      by responses. Variations in the interval between shocks and changes in shock
      intensity over a wide range did not attenuate responding. Terminal performance
      was characterized by a consistent pattern of shock-elicited responses. Responses
      were also elicited by a tone following repeated tone-shock pairings. Finally,
      responding that was maintained by response-independent shocks was quickly
      suppressed by response-contingent shocks of the same intensity.

PMID- 16811412
TI  - Schedules using noxious stimuli. IV: An interlocking shock-postponement schedule
      in the squirrel monkey.
AB  - Responding was studied under various schedules of electric shock postponement and
      presentatation in the squirrel monkey. Under an interlocking shock-postponement
      schedule, successive responses decreased the time by which a response postponed
      the next scheduled shock until a shock immediately followed the nth response.
      Some parameters of this schedule, which can be formally related to fixed-interval
      schedules, engendered a pattern of positively accelerated responding between
      shocks. This pattern did not occur under comparable parameter values of an
      alternative fixed-ratio, avoidance schedule under which each response postponed
      shock by a fixed duration and every nth response produced shock. Subsequently,
      performances were studied under schedules of shock presentation. Responding was
      never maintained under fixed-ratio schedules of shock presentation, but was
      maintained with a pattern of positive acceleration under an alternative fixed
      ratio, fixed-interval schedule and under a fixed-interval schedule.

PMID- 16811413
TI  - Editorial: On the vocabulary and the grammar of behavior.

PMID- 16811414
TI  - The control of feeding behavior by an imprinted stimulus.
AB  - Imprinted ducklings were trained to peck a pole using brief presentations of the
      imprinted stimulus as the response-contingent (reinforcing) event. Subjects were
      then permitted to spend extended periods with continuous access to food and the
      imprinted stimulus (via a pole peck). For other (control) subjects the
      experimental situation was restricted to either responding for the stimulus, or
      feeding in the absence of the stimulus. For subjects in the control conditions,
      both activities occurred in cyclic fashion. When, however, there was continuous
      opportunity to respond for the stimulus and food was available, the tendency to
      respond was related to the tendency to feed. Other experiments showed that
      independent presentations of the stimulus could initiate feeding in imprinted
      ducklings with no prior pairing of the stimulus with food and with no prior pole
      peck training. The most consistent control over feeding, however, was exhibited
      by ducklings that were imprinted and also accustomed to periodic removals of the
      stimulus. It is concluded that in ducklings, imprinting procedures are sufficient
      to endow an arbitrary stimulus with the capacity to release feeding behavior.

PMID- 16811415
TI  - Choice as time allocation.
AB  - When pigeons' standing on one or the other side of a chamber was reinforced on
      two concurrent variable-interval schedules, the ratio of time spent on the left
      to time spent on the right was directly proportional to the ratio of
      reinforcements produced by standing on the left to reinforcements produced by
      standing on the right. The constant of proportionality was less than unity for
      all pigeons, indicating a bias toward the right side of the chamber. The biased
      matching relation obtained here is comparable to the matching relation obtained
      with concurrent reinforcement of key pecks. The present results, together with
      related research, suggest that the ratio of time spent in two activities equals
      the ratio of the "values" of the activities. The value of an activity is the
      product of several parameters, such as rate and amount of reinforcement,
      contingent on that activity.

PMID- 16811416
TI  - Interval reinforcement of choice behavior in discrete trials.
AB  - Pigeons were trained to peck at red or green keys presented simultaneously in
      discrete trials. In one experiment, reinforcements were arranged by concurrent
      variable-interval schedules. The proportion of responses to green approximately
      matched the proportion of reinforcements produced by pecking green. Detailed
      analysis of responding revealed a systematic decrease in the probability of
      switching from green to red within sequences of trials after reinforcement. This
      trend corresponded to sequential changes in the relative frequency of
      reinforcement, and not to sequential changes in probability of reinforcement. In
      a second experiment, reinforcements were scheduled probabilistically every
      seventh trial. Even though there were no contingencies on pecking during the
      first six post-reinforcement trials, choices of green on the first response after
      reinforcement matched the proportion of reinforcements for pecking green. These
      results extend the generality of overall matching under concurrent reinforcement.

PMID- 16811417
TI  - Concurrent responding with fixed relative rate of reinforcement.
AB  - Responding by pigeons on one key of a two-key chamber alternated the color of the
      second key, on which responding produced food according to a variable-interval
      schedule of reinforcement. From time to time, reinforcement would be available
      for a response, but in the presence of a particular stimulus, either red or green
      light on the key. Red or green was chosen irregularly from reinforcement to
      reinforcement, so that a proportion of the total number of reinforcements could
      be specified for each color. Experimental manipulations involved variations of
      (1) the proportions for each color, (2) changeover delay, or, alternatively, (3)
      a fixed-ratio changeover requirement. The main findings were: (1) relative
      overall rates of responding and relative times in the presence of a key color
      approximated the proportions of reinforcements obtained in the presence of that
      color, while relative local rates of responding changed little; (2) changeover
      rate decreased as the proportions diverged from 0.50; (3) relative overall rate
      of responding and relative time remained constant as the changeover delay was
      increased from 2 to 32 sec, with reinforcement proportions for red and green of
      0.75 and 0.25, but they increased above 0.90 when a fixed-ratio changeover of 20
      responses replaced the changeover delay; (4) changeover rate decreased as the
      delay or fixed-ratio was increased.

PMID- 16811418
TI  - Behavioral contrast in chained schedules.
AB  - In each of two experiments, the rate of key pecking maintained by a variable
      interval food reinforcement schedule was measured, first when that schedule was
      studied in isolation, and then when it was correlated with the second component
      of a two-component chained schedule. In the first experiment, the first component
      of the chained schedule was correlated with a fixed-interval schedule; in the
      second experiment it was correlated with a variable-interval schedule. In both
      experiments, behavioral contrast was demonstrated in the second component of the
      chained schedule. Compared to the rate of responding on the food-reinforcement
      schedule when it had operated in isolation, the rate of responding on the food
      reinforcement schedule when it was correlated with the second component was
      higher, while the rate on the schedule of the first component was lower. The
      results are discussed with reference to the determinants of contrast.

PMID- 16811419
TI  - Attention and generalization during a conditional discrimination.
AB  - A conditional discrimination was established and analyzed, using four pigeons.
      The discrimination was among four compound stimuli projected on the response key
      a white circle or triangle on a red or green background-during two conditions of
      illumination in the chamber, no illumination or flashing illumination. The two
      lighting conditions indicated whether the stimuli on the key containing triangles
      or those containing red would be the occasion for reinforcement. After the
      discrimination formed, generalization to intermediate and extreme values of the
      conditional stimulus and the attention of the birds to separate aspects of the
      stimulus on the key under each of the conditional stimuli were studied. All
      subjects generalized across values of the conditional stimulus, the lighting of
      the chamber. But subjects differed in the manner in which they treated the
      compound stimuli: two tended to attend to one or the other aspect of the stimulus
      on the key depending on the conditional stimulus, and two offered no evidence of
      such selective attention. Thus, the differential control of responding by the
      conditional stimuli cannot be attributed to a shift in attention between the
      figure and ground aspects of the compound stimuli.

PMID- 16811420
TI  - Aversive properties of the negative stimulus in a successive discrimination.
AB  - Experiment I sought to determine if the stimulus correlated with extinction in a
      successive discrimination was an aversive stimulus. An escape response provided
      an index of aversive control. Two groups of pigeons were exposed to a multiple
      variable-interval 30-sec extinction schedule. For the experimental group, a
      single peck on a second key produced a timeout during which all lights in the
      chamber were dark. For the control group, pecks on the second key had no
      contingency. The rate of responding on the timeout key during extinction for the
      experimental group was higher than that of the control group during all sessions
      of discrimination training except the first. In Exp. II, green was correlated
      with variable interval 30-sec and red was correlated with variable-interval 5
      min. Timeouts were obtained from variable-interval 5-min. There were more
      timeouts from extinction in Exp. I than from variable-interval 5-min in Exp. II.
      Experiment III showed that not presenting the positive stimulus reduced the
      number of timeouts from the negative stimulus for the two birds from Exp. I that
      had the highest rate of timeouts from extinction, but had little effect on the
      two birds that had the lowest rate of timeouts. These results suggest that in a
      multiple schedule, the stimulus correlated with extinction, or the lower response
      rate, functions as a conditioned aversive stimulus. Explanations of the timeout
      response in terms of extinction produced variability, displaced aggression, and
      stimulus change, were considered but found inadequate.

PMID- 16811421
TI  - Some variables affecting the superstitious chaining of responses.
AB  - This study was based upon a repeated acquisition technique that systematically
      generated superstitious chains of responses. Several procedures were investigated
      in an effort to modify the amount of superstitious chaining. The effects of a
      large work requirement, a stimulus correlated with non-reinforcement after
      inappropriate responses, an equivalent time delay after inappropriate responses,
      and extensive training were examined. The presentation of a stimulus correlated
      with non-reinforcement was found to be the most effective technique for reducing
      superstitious chaining; the time delay was the least effective.

PMID- 16811422
TI  - Collateral responding during differential reinforcement of low rates.
AB  - Two pigeons were trained to peck either of two response keys for food, under two
      different variable-interval schedules. When responding stabilized, the schedule
      on the left key (reinforcement-key) was changed to a differential-reinforcement
      of-low-rates schedule, and responses on the right key (extinction-key) were no
      longer reinforced. The mean interresponse time of responses on the reinforcement
      key approximated the temporal requirement of the reinforcement schedule on that
      key. Collateral responding on the extinction-key was maintained by one of the
      birds. A "run" of these collateral responses was defined as a sequence of
      responses on the extinction-key occurring between two responses on the
      reinforcement-key. For this one bird, collateral behavior, measured by mean time
      per run and mean number of responses per run, was an increasing function of the
      temporal requirements of the reinforcement schedule on the reinforcement key, and
      it was strongly positively correlated with the mean interresponse time of
      responses on the reinforcement-key. However, from an analysis of the results, the
      collateral behavior did not appear to have mediated the temporal spacing of
      responses on the reinforcement-key.

PMID- 16811424
TI  - An analysis of the experimental analysis of behavior (TEAB).

PMID- 16811423
TI  - The concurrent reinforcement of two interresponse times: absolute rate of
      reinforcement.
AB  - Three pigeons obtained food on a one-key schedule of reinforcement for two
      concurrent, discriminated interresponse times. The overall rate of reinforcement
      was determined by a family of variable-interval schedules and by a continuous
      reinforcement schedule. The average frequency of reinforcement varied from 1.1 to
      300 reinforcements per hour; the relative frequency of reinforcement for each of
      the two interresponse times was 0.5 throughout the experiment. The number of
      responses per minute increased sharply as the number of reinforcements per hour
      increased from 1 to 20. Beyond 30 reinforcements per hour, the curve was
      approximately flat, although it sometimes decreased slightly at the highest
      reinforcement rates. The relative frequency of the shorter interresponse time
      also increased sharply as the number of reinforcements per hour increased from 1
      to 20. The asymptote of the relative frequency function approximately equalled
      the relative reciprocal of the length of the shorter interresponse time for
      reinforcement rates greater than 30 or 40 reinforcements per hour. This
      approximation was obscured by the response-rate function.

PMID- 16811425
TI  - A response-initiated fixed-interval schedule of reinforcement.
AB  - On a tandem fixed-ratio one fixed-interval schedule, the first response after
      reinforcement initiates a fixed interval of time and the first response after the
      interval has elapsed is reinforced. Pigeons trained with that schedule of food
      reinforcement paused after reinforcement for a period of time that approximated
      the fixed-interval duration for values of that duration ranging from 3.75 to 60
      sec. Cumulative records revealed response patterns best described as break-and
      run.

PMID- 16811426
TI  - DRL escape: effects of minimum duration and intensity of electric shock.
AB  - Three dogs were exposed to a DRL-escape procedure that required them to endure a
      minimum duration of electric shock without responding in order for a response to
      terminate that shock. When this minimum duration increased from 0 to either 2.25
      or 7.00 sec, response latencies increased proportionately. With the minimum
      duration held constant at 2.25 sec, a gradual increase in shock intensity to 5.0
      ma had no systematic effect upon latencies. Even under the highest shock
      intensity, 5.0 ma, latency and interresponse-time distributions were unimodal
      with very few latencies and interresponse times less than the minimum duration.
      Three additional dogs were exposed to an escape procedure in which every response
      was immediately reinforced. For these subjects, the same increase in shock
      intensity to 5.0 ma was accompanied by a decrease in latencies. The precise
      temporal spacing of responses obtained with the DRL-escape procedure may in part
      be due to the fact that every response latency and interresponse time that did
      not meet the minimum duration was not only extinguished but was also punished.

PMID- 16811427
TI  - The elimination of interfering response patterns in lever-press avoidance
      situations.
AB  - Lever holding into shock and short-latency responses to shock onset are two
      response patterns that interfere with avoidance acquisition in free-operant and
      discriminated avoidance situations. In an attempt to eliminate these patterns, an
      additional timer disabled the lever for a period slightly longer than shock
      duration. A free-operant avoidance schedule with a warning stimulus, but without
      the additional timer, constituted the control condition. The lever-disabling
      timer was turned on by different events in two experimental conditions: (a)
      release of the lever at the onset of shock, (b) shock onset. Interfering
      responses diminished most rapidly, and efficient avoidance behavior appeared
      earliest, when the lever-disabling timer was turned on by shock onset.

PMID- 16811428
TI  - A choice technique to assess the effects of selective punishment on fixed-ratio
      performance.
AB  - The emission of a fixed number of responses by rats was followed by food
      reinforcement. This fixed number could be accumulated in any way from two
      continuously available but mutually incompatible response classes, bar pressing,
      and not bar pressing for a fixed time period. A preference for one response class
      was arranged by specifying different maximum reinforcement rates for the two
      classes. Under selective punishment conditions, the preferred response
      occasionally led to both food and electric shock, while the non-preferred
      response led only to food. Selective punishment effects were measured through
      changes in the preference to the two responses in the sequence. The actions of
      shock intensity, deprivation, the specification of the non-preferred response,
      and three drugs were investigated. The results were broadly similar to the work
      reported by Dardano and Sauerbrunn (1964), who found localized increases in
      interresponse times before punished responses in fixed-ratio schedules.
      Performance under this procedure was found to be stable and sensitive to each of
      the experimental variables examined.

PMID- 16811429
TI  - A multipurpose switching device with independently timed N.O. and N.C. states.

PMID- 16811430
TI  - Effect of reinforcement duration on fixed-interval responding.
AB  - Five different reinforcement durations occurred randomly within each session on
      fixed interval 60-sec. Postreinforcement pause was directly related (and
      "running" rate inversely related) to the duration of reinforcement initiating
      each fixed interval.

PMID- 16811431
TI  - Timing in free-operant and discrete-trial avoidance.
AB  - A procedure ("discrete-trial" avoidance) was devised to differentiate between the
      two main theories of responding in Sidman's "free-operant" avoidance procedure.
      One theory, a version of two-factor theory, holds that responding is reinforced
      by the removal of a conditioned aversive stimulus. The conditioned aversive
      stimulus is held to be temporal, which accounts for the spaced responding, or
      timing, that Sidman's procedure produces. The other theory holds that the
      reinforcement for both responding and timing is shock-frequency reduction. The
      new procedure eliminated this reinforcement for timing, but retained the
      conditions for the formation of conditioned aversive temporal stimuli. According
      to one theory, the new procedure should have sustained timing as well as
      Sidman's, while according to the other, it should have sustained no timing. The
      results confirmed neither theory. Timing was found with both procedures, but
      unequally in degree and kind. Large variations in the precision of timing did not
      appear to be correlated with successful avoidance for either procedure.

PMID- 16811432
TI  - Superstitious key pecking after three peck-produced reinforcements.
AB  - The first three pecks on a response key by experimentally naive pigeons produced
      grain reinforcements. Thereafter, for approximately 50 experimental sessions and
      under a variety of schedule conditions, grain was presented independently of the
      subjects' behaviors. The pigeons continued to peck the response key
      "superstitiously" throughout the 50 sessions. The results suggest that
      superstitions are commonplace-not relatively infrequent or abnormal events-in the
      behavior of pigeons.

PMID- 16811433
TI  - A multifunction pulseforming circuit.

PMID- 16811434
TI  - The effect of a fading procedure upon the acquisition of control by an
      overshadowed auditory feature.
AB  - Pigeons' key-pecking responses were reinforced in the presence of a compound
      stimulus that consisted of an auditory feature (a tone) and a visual feature (a
      light) and non-reinforced in the presence of a compound stimulus that was either
      a noise and a dark key, or noise and a light. In the condition where
      reinforcement trials differed from non-reinforcement trials on the basis of both
      auditory and visual features, the tone exerted very little control over
      responding on test. In the condition where reinforcement differed from non
      reinforcement trials solely on the basis of the auditory features, an abrupt and
      a gradual introduction of the visual feature of the negative stimulus, a light,
      were compared for their effect upon control in the compounds. The tone acquired
      strong control in both cases. Evidence indicated that the tone had acquired
      control in the gradual condition without the occurrence of responses to the
      negative stimulus. An incidental finding was that when the negative stimulus
      consisted of a noise and a light, which was introduced abruptly, responding over
      the light dimension with tone, on test, was peaked at a point other than that
      light value used as positive and negative during training.

PMID- 16811435
TI  - Choice, rate of reinforcement, and the changeover delay.
AB  - Pigeons distribute their responses on concurrently available variable-interval
      schedules in the same proportion as reinforcements are distributed on the two
      schedules only when a changeover delay is used. The present study shows that this
      equality between proportions of responses and proportions of reinforcements
      ("matching") is obtained when the value of the changeover delay is varied. When
      responses are partitioned into the set of rapid response bursts occurring during
      the delay interval and the set of responses occurring subsequently, the
      proportion of neither set of responses matches the proportion of reinforcements.
      Instead, each set deviates from matching but in opposite directions. Matching on
      the gross level results from the interaction of two patterns evident in the local
      response rates: (I) the lengthening of the changeover delay response burst is
      accompanied by a commensurate decrease in the number of changeovers; (2) the
      changeover delay response burst is longer than the scheduled delay duration. When
      delay responses are eliminated by introducing a blackout during the delay
      interval, response matching is eliminated; the pigeon, however, continues to
      match the proportion of time spent responding on a key to the proportion of
      reinforcements obtained on that key.

PMID- 16811436
TI  - Summation of responding maintained by fixed-interval schedules.
AB  - A light and tone were separately correlated with responding maintained by fixed
      interval schedules, in which the level of responding varied continuously
      throughout the duration of the interval. Responding during the presence of the
      single stimuli and their compound was compared during the successive segments of
      the interval. The following results were obtained: (1) more responses were
      emitted during compounding than were emitted during either stimulus alone in all
      segments of the interval; (2) increases in the number of responses across the
      interval during compounding paralleled increases during single-stimulus
      presentations. The sum of the responses emitted during the single stimuli was
      similar to the number of responses emitted during compounding, suggesting that
      the response tendencies correlated with the single stimuli combined in a
      summative or additive fashion.

PMID- 16811437
TI  - Operant acceleration during a pre-reward stimulus.
AB  - Stimuli of 20, 40, and 80 sec duration terminated with five non-response
      contingent food pellets were superimposed upon lever pressing reinforced with
      single pellets on a DRL 30-sec schedule. Two rhesus monkeys served as subjects.
      No change in response frequency was observed during the 20- and 40-sec stimuli.
      During the 80-sec pre-food stimulus, overall response frequency increased to
      approximately 150% and 220% of pre-stimulus levels, and the temporal
      distributions of interresponse times shifted toward the shorter intervals. When
      the 80-sec stimulus was no longer terminated with food, the response frequency
      decreased and the temporal distributions of interresponse times gradually
      approached pre-stimulus levels. An increased frequency of short interresponse
      times and an increase in response rate was again observed when the pellet
      termination procedure was reinstituted with the 80-sec stimulus. No change in
      response frequency or interresponse times was observed in the absence of the
      conditioning stimulus, and performance efficiency, as reflected in the ratio of
      responses to reinforcements during non-stimulus periods, remained stable
      throughout the experiment.

PMID- 16811438
TI  - Free-operant avoidance in the pigeon using a treadle response.
AB  - A free-operant avoidance schedule was used to establish and maintain foot-treadle
      responding by two Homing, one White King, and two Carneaux pigeons. In the
      absence of responding, the interval between shocks equaled 10 sec. Each time a
      treadle response occurred the shock was postponed for 32 sec. Pigeons appear to
      learn the treadle response more quickly and use it to avoid shock more
      successfully than do rats bar pressing on similar schedules. The treadle response
      becomes highly stereotyped and interresponse time distributions obtained from
      terminal behavior appear very similar to data obtained from rats. It is concluded
      that the difficulty in training pigeons to avoid electric shock is not in
      establishing avoidance behavior but in attempting to evaluate such behavior with
      the key-peck response.

PMID- 16811439
TI  - Some punishing effects of response-force.
AB  - The present experiment explored the punishing effect of different response-force
      requirements by means of a two-operant design analogous to a two-component chain
      schedule. The first component of the chain required a lever pull through 0.25 in.
      (0.64 cm) at 1 lb (4.45 N) of force. The second component required a lever pull
      through an additional 0.75 in. (1.90 cm) with the force varied between sessions
      from 1 lb to 50 lb (4.45 N to 223 N). Completion of the second component of the
      chain was reinforced after variable intervals averaging 1 min. The average rate
      of first-component response decreased as the force requirement for second
      component responses was increased. This rate reduction did not appear to be due
      to increased response duration, "fatigue", or differing rates of reinforcement.
      If the force requirement for the second-component response is viewed as a
      consequence for the first-component response, then the results of the experiment
      show that a high force requirement is a punisher.

PMID- 16811440
TI  - On the law of effect.
AB  - Experiments on single, multiple, and concurrent schedules of reinforcement find
      various correlations between the rate of responding and the rate or magnitude of
      reinforcement. For concurrent schedules (i.e., simultaneous choice procedures),
      there is matching between the relative frequencies of responding and
      reinforcement; for multiple schedules (i.e., successive discrimination
      procedures), there are contrast effects between responding in each component and
      reinforcement in the others; and for single schedules, there are a host of
      increasing monotonic relations between the rate of responding and the rate of
      reinforcement. All these results, plus several others, can be accounted for by a
      coherent system of equations, the most general of which states that the absolute
      rate of any response is proportional to its associated relative reinforcement.

PMID- 16811441
TI  - A preliminary analysis of the dynamics of the pecking response in pigeons.
AB  - The pecking response of pigeons is usually measured by a transducer that senses
      the presence or absence of a response. Typically, the response force as a
      function of time has not been accurately measured. Data were collected using a
      transducer specially designed to record the waveform of the pecking response in
      pigeons. Each response on the target surface of the transducer was reinforced and
      followed by a blackout. The response was stored on an oscilloscope screen and the
      peak force and duration of the response were recorded manually from the
      oscilloscope screen. The mean peak force of the response substantially exceeded
      the minimum criterion for reinforcement of 35 g (0.343 Newtons) of force.
      Photographs of the waveform of pecks on the transducer showed great variability
      in response force and demonstrated that the waveform produced by pecking the
      target surface was complex. The responses were frequently asymmetrical with the
      rise time shorter than the fall time, although no single verbal description could
      be applied to all of the waveforms. Bimodal peaks and double responses were
      observed and the first peck or response was usually larger than the second. A
      disadvantage of the transducer was that pecking produced oscillation of the
      transducer at its resonant frequency. In spite of this deficiency, the waveform
      of the peck was easily recognizable.

PMID- 16811442
TI  - A shaping technique for producing rapid and reliable Sidman bar-press avoidance.

PMID- 16811443
TI  - Signalled and unsignalled free-operant avoidance in the pigeon.
AB  - Pigeons were trained to depress a lever to avoid electric shock under free
      operant avoidance schedules without a warning signal, or with a warning signal
      that could be terminated only by a response. Most birds in the signalled
      avoidance procedure terminated more than 50% of the warning signals before shock.
      In the unsignalled avoidance procedure, several birds formed a temporal
      discrimination and received relatively few shocks; other birds responded only in
      post-shock bursts, and received many more shocks.

PMID- 16811444
TI  - An automated multiple choice test of short-term spatial memory for monkeys.

PMID- 16811445
TI  - Relative frequency of reinforcement and rate of punished behavior.
AB  - After training on a multiple variable-interval variable-interval schedule of
      reinforcement, each response in one component of the schedule was followed by a
      brief electric shock. When the rate of punished responses stabilized, the
      frequency of reinforcement in the other component was first decreased and then
      increased from the baseline frequency. The effects of these manipulations were
      consistent with reports of interactions in multiple schedules involving only
      unpunished behavior, i.e., the rate of punished responses increased with a higher
      relative frequency of reinforcement in the punishment component and decreased
      with a lower relative frequency of reinforcement in that component. The relevance
      of such findings to a further generality of behavioral contrast effects is
      discussed.

PMID- 16811446
TI  - Titration schedule with rats in a restraining device.
AB  - In a restraining device, providing a constant localization and easy placement of
      stimulating electrodes, rats were conditioned to push a front panel in order to
      reduce the intensity of a shock which otherwise increased regularly every 10 sec.
      Rapid conditioning was obtained from all subjects. They showed a very stable
      behavior, with negligible inter- or intra-individual variability throughout very
      long experimental sessions. The operant nature of the response was demonstrated
      further in extinction, where no shock was delivered, and in situations where the
      animal could not change the predetermined intensity of the shock. The
      interpretation of the obtained threshold was discussed with reference to previous
      studies on titration schedule. It was suggested that, with the parameters used,
      the shock intensity at which it was maintained by the rats' behavior, had the
      value of a warning signal, and that, in this particular case, the titration
      schedule generated mainly discriminative avoidance behavior rather than escape
      behavior.

PMID- 16811447
TI  - Schedule-induced polydipsia: are response-dependent schedules a limiting
      condition?
AB  - The collateral water intake of albino rats was measured when the inter-pellet
      intervals in fixed-ratio and fixed-time schedules were equated. Fixed-ratio and
      fixed-time inter-pellet intervals were equated by dividing the average fixed
      ratio session time of each subject by 150 (food pellets). The average inter
      pellet interval obtained then defined the subsequent fixed-time schedule for each
      individual subject. Shifts to fixed-time schedules followed the completion of
      each fixed-ratio 20, 40, and 80 schedule. This procedure permitted an assessment
      of the extent to which excessive collateral drinking was associated with inter
      pellet interval length or adventitious food reinforcement. For both the fixed
      ratio and fixed-time schedules, drinking progressively increased as a function of
      increasing the duration of the inter-pellet interval and was a post-pellet event
      under the control of variables other than adventitious food reinforcement.

PMID- 16811448
TI  - A response duration schedule: effects of training, extinction, and deprivation.
AB  - Rats were trained to hold down a lever for at least 40 consecutive seconds. When
      the lever had been held down for 40 sec, white noise came on. Releasing the bar
      in the presence of the noise turned off the noise and operated a feeder that
      delivered a pellet of food. At the end of training, frequency distributions of
      response durations peaked at 40 to 41 sec. If as in training, holding down the
      lever produced white noise at the end of 40 sec, and release of the lever
      terminated the noise and operated the feeder, but no food delivery occurred,
      duration distributions and several other measures were initially not very
      different from when food was delivered. However, if during extinction white noise
      was never produced by lever holding, and feeder operation did not occur upon
      lever release, most responses were shorter than 1 sec in duration, some were much
      longer than 41 sec, and duration distributions did not peak at 40 to 41 sec. When
      reinforcement was reinstated after extinction, performance quickly returned to
      pre-extinction measures. Further sessions at different levels of deprivation
      produced only temporary disruptions in performance.

PMID- 16811449
TI  - Inexpensive pubis electrodes for delivering shock to pigeons.

PMID- 16811450
TI  - A comparison of variable-ratio and variable-interval schedules of reinforcement.
AB  - Four pigeons responded under a two-component multiple schedule of reinforcement.
      Responses were reinforced in one component under a variable-ratio schedule and in
      the other component under a variable-interval schedule. It was found that when
      rates of reinforcement were equal in the two components, the rate of response in
      the variable-ratio component was nearly twice that in the variable-interval
      component. Furthermore, for three of the four subjects, the function relating
      response rate to relative rate of reinforcement in the variable-ratio component
      had a slope 2.5 to 3 times the slope of the corresponding function for the
      variable-interval component.

PMID- 16811451
TI  - Effects of a conditioned reinforcer upon accuracy of match-to-sample behavior in
      pigeons.
AB  - Three pigeons were trained to perform a two-key sequential match-to-sample task.
      During baseline conditions, food reinforcement was contingent upon the first
      match response to occur following 8-min periods, and orange illumination of both
      keys preceded the delivery of food by 0.5 sec. The baseline schedule of food
      reinforcement was in effect throughout the study. In some conditions, a 0.5-sec
      flash of orange keylight alone was presented contingent upon mismatch responses
      that followed variable time periods averaging 1 min. Rate of mismatch responses
      increased and accuracy of matching performances decreased as compared with
      baseline conditions. The ability of the 0.5-sec orange flash to reinforce
      mismatch responses was markedly reduced when it no longer immediately preceded
      the delivery of food.

PMID- 16811452
TI  - Pigeon concept formation: successive and simultaneous acquisition.
AB  - Pigeons were trained to discriminate the presence of one or more human forms in
      displays projected on a panel above the response key. This task was mastered,
      although imperfectly, with successive and with simultaneous presentations of
      positive and negative instances. The course of acquisition of the discrimination
      was similar for the two training procedures. Animals were able to transfer the
      discrimination from the successive to the simultaneous situation. Various tests
      were carried out to control for artifactual cues on which the discrimination
      might have been based. The discrimination was maintained when new displays were
      presented, when reinforcement was omitted, and when displays were inverted 180
      degrees . Animals were also able to discriminate between pairs of displays that
      were identical, except that one member of the pair contained a human form. The
      research extends the techniques used by Herrnstein and Loveland (1964), and
      confirms their finding that pigeons can master the concept of "person-present" in
      a visual display.

PMID- 16811453
TI  - Instructional control of human operant responding during extinction following
      fixed-ratio conditioning.
AB  - When given pre-conditioning instructions correctly indicating the maximum number
      of reinforcements obtainable, subjects made few responses during extinction
      following FR 10 conditioning. More extinction responses occurred when the maximum
      reinforcement instructions suggested that reinforcements were obtainable during
      extinction. The highest rates of responding during extinction were produced by
      subjects who had no maximum-reinforcement instructions.

PMID- 16811454
TI  - Responding under fixed-ratio and multiple fixed-interval fixed-ratio schedules of
      electric shock presentation.
AB  - Squirrel monkeys, initially trained under a schedule of electric shock
      postponement and then under fixed-interval schedules of electric shock
      presentation, were studied under multiple fixed-interval fixed-ratio and under
      fixed-ratio schedules of shock presentation. Under the fixed-interval (10-min)
      component of the multiple schedule, a pause was followed by a gradual increase in
      responding to a rate maintained until shock presentation; under the fixed-ratio
      (3-, 10-, or 30-response) component of the multiple schedule, a brief pause was
      typically followed by a relatively high and uniform rate of responding until
      shock was presented. When the 60-sec timeout periods, which usually followed
      shock presentation, were eliminated from the multiple schedule for one monkey,
      responding was only transiently affected. In the one monkey studied, responding
      was maintained under a fixed-ratio schedule alone (with timeout periods), but
      rates of responding were lower than under the fixed-ratio component of the
      multiple schedule. Characteristic patterns of responding, similar to those
      engendered under schedules of food presentation or shock termination, can be
      maintained under fixed-ratio schedules of shock presentation; further, patterns
      of responding can be controlled by discriminative stimuli in multiple schedules.

PMID- 16811455
TI  - Conditioned reinforcement and discrimination performance.
AB  - Pigeons were trained in a three-key chamber to peck one side key in the presence
      of a vertical line on the center key and to peck the other side key in the
      presence of a horizontal line. Correct choice responses were reinforced with food
      according to fixed- and variable-ratio, fixed-interval, and differential
      reinforcement-of-long-latency schedules of reinforcement. For each schedule, the
      birds performed under each of two conditions: (1) each correct choice response
      produced a brief presentation of stimuli intermittently paired with food, then
      the next trial; (2) each correct choice response produced an intertrial interval
      only. For all schedules except one long latency schedule, response rates were
      higher under the condition of brief stimulus presentation than under the
      comparable control condition. Presentation of brief magazine stimuli increased
      choice accuracy. The amount of change in accuracy was correlated with the rate of
      food presentation. Performance under the schedules with highest food
      reinforcement rates showed no enhancement; performance under the schedules with
      the lowest reinforcement rates showed the greatest enhancement.

PMID- 16811456
TI  - Interresponse time duration in fixed-interval schedules of reinforcement: control
      by ordinal position and time since reinforcement.
AB  - The times between each of the first thirteen responses after reinforcement (the
      first twelve interresponse times) were determined for two pigeons whose pecking
      was reinforced on fixed-interval schedules of food reinforcement ranging from 0.5
      min to 5 min. These interresponse times were classified with respect to their
      ordinal position in the sequence of responses and with respect to the time since
      the preceding reinforcement at which the initiating response occurred. The median
      interresponse time durations were essentially constant after the sixth response
      after reinforcement regardless of the time at which the interresponse time was
      initiated. The durations of the first few interresponse times after reinforcement
      decreased as the number of preceding responses increased and as the time since
      the preceding reinforcement increased.

PMID- 16811457
TI  - The response-reinforcement dependency in fixed-interval schedules of
      reinforcement.
AB  - Pigeons were exposed to four different schedules of food reinforcement that
      arranged a fixed minimum time interval between reinforcements (60 sec or 300
      sec). The first was a standard fixed-interval schedule. The second was a schedule
      in which food was presented automatically at the end of the fixed time interval
      as long as a response had occurred earlier. The third and fourth schedules were
      identical to the first two except that the first response after reinforcement
      changed the color on the key. When the schedule required a peck after the
      interval elapsed, the response pattern consisted of a pause after reinforcement
      followed by responding at a high rate until reinforcement. When a response was
      not required after the termination of the interval, the pattern consisted of a
      pause after reinforcement, followed by responses and then by a subsequent pause
      until reinforcement. Having the first response after reinforcement change the
      color on the key had little effect on performance. Post-reinforcement pause
      duration varied with the minimum interreinforcement interval but was unaffected
      by whether or not a response was required after the interval elapsed.

PMID- 16811458
TI  - Two-key concurrent responding: response-reinforcement dependencies and blackouts.
AB  - Two-key concurrent responding was maintained for three pigeons by a single
      variable-interval 1-minute schedule of reinforcement in conjunction with a random
      number generator that assigned feeder operations between keys with equal
      probability. The duration of blackouts was varied between keys when each response
      initiated a blackout, and grain arranged by the variable-interval schedule was
      automatically presented after a blackout (Exp. I). In Exp. II every key peck,
      except for those that produced grain, initiated a blackout, and grain was
      dependent upon a response following a blackout. For each pigeon in Exp. I and for
      one pigeon in Exp. II, the relative frequency of responding on a key
      approximated, i.e., matched, the relative reciprocal of the duration of the
      blackout interval on that key. In a third experiment, blackouts scheduled on a
      variable-interval were of equal duration on the two keys. For one key, grain
      automatically followed each blackout; for the other key, grain was dependent upon
      a response and never followed a blackout. The relative frequency of responding on
      the former key, i.e., the delay key, better approximated the negative exponential
      function obtained by Chung (1965) than the matching function predicted by Chung
      and Herrnstein (1967).

PMID- 16811459
TI  - Choice for periodic schedules of reinforcement.
AB  - Pigeons' responses in the presence of two concurrently available (initial-link)
      stimuli produced one of two different (terminal-link) stimuli according to
      identical but independent variable-interval schedules. Responding in the mutually
      exclusive terminal links was reinforced with food according to fixed-ratio
      schedules for six pigeons and according to fixed-interval schedules for two
      pigeons. None of the pigeons matched the proportion of (choice) responses in the
      initial links to the proportion of the rates of reinforcement obtained during the
      terminal links. Instead, as the values of each of the terminal-link schedules
      were increased by a constant amount, the choice proportions for the stimulus
      associated with the smaller of the two values increased, even though the relative
      rates of reinforcement during the terminal links decreased. These results are
      incompatible with those from previous studies with aperiodic (variable-interval
      or variable-ratio) schedules. The present results do suggest, however, that in
      transforming aperiodic schedules into their periodic equivalents, it may be
      necessary to consider the size of the smallest interreinforcement interval
      comprising the terminal-link schedules.

PMID- 16811460
TI  - Factors influencing inhibitory stimulus control: differential reinforcement of
      other behavior during discrimination training.
AB  - Pigeons were trained to respond on a multiple variable-interval 1-min variable
      interval 1-min schedule, then switched to a multiple variable-interval 1-min
      differential-reinforcement-of-other-behavior discrimination training. The rate of
      reinforcement was held constant during the shift from non-differential
      reinforcement to discrimination training. Behavioral contrast and post
      discrimination inhibitory stimulus control followed the observation of a
      reduction in the rate of responding to the stimulus correlated with reinforcement
      for the non-occurrence of pecking.

PMID- 16811461
TI  - Unbiased and unnoticed verbal conditioning: the double agent robot procedure.
AB  - Subjects who were told they were "experimenters" attempted to reinforce fluent
      speech in a supposed subject with whom they spoke via intercom. The supposed
      subject was to say nouns, one at a time, on request by the "experimenter", who
      reinforced fluent pronunciation with points. Actually, the "experimenter" was
      talking to a multi-track tape recording, one track of which contained fluently
      spoken nouns, the other track containing disfluently spoken nouns. If the
      "experimenter's" request for the next noun was in a specified form a word from
      the fluent track was played to him as reinforcement; requests in any other form
      produced the word from the disfluent track. Repeated conditioning of specific
      forms of requests was accomplished with two subject-"experimenters," who were
      unable to describe changes in their own behavior, or the contingencies applied.
      This technique improved upon an earlier method that had yielded similar results,
      but was less thoroughly controlled against possible human bias.

PMID- 16811462
TI  - Preference for fixed-interval schedules of reinforcement.
AB  - Pigeons were trained on a two-link concurrent chain schedule in which responding
      on either of two keys in the initial link occasionally produced a terminal link,
      signaled by a change in the color of that key and a darkening of the other.
      Further responding on the lighted key was reinforced with food according to a
      fixed-interval schedule. For one of the keys, this fixed interval was always 20
      sec, while for the other it was held at values of 5, 14, 30, or 60 sec for
      several weeks. In the initial link, all pigeons responded relatively more often
      on the key with the shorter fixed interval than was predicted by the matching
      hypothesis. Responding in the initial link showed a large negative recency
      effect: pigeons responded less frequently on the key that provided their last
      reinforcement than predicted from the overall response rates.

PMID- 16811463
TI  - Inhibitory stimulus control in concurrent schedules.
AB  - Six pigeons were exposed to two keys, a main key and a changeover key. Pecking
      the main key was reinforced on a variable-interval 5-min schedule when the key
      was blue and never reinforced when the key displayed a vertical line on a blue
      background. Each peck on the changeover key changed the stimulus displayed on the
      main key. Each subject was given two generalization tests, consisting of
      presentations on the main key of six orientations of the line on the blue
      background, with no reinforcements being given. In one test changeover-key pecks
      changed the stimulus; in the other test the changeover key was covered and the
      experimenter controlled stimulus changes. Both responses to the six stimuli and
      time spent in the presence of the stimuli gave U-shaped gradients when the
      changeover key was operative. With most subjects, absolute rates of responding to
      each stimulus produced unsystematic gradients, whether or not the changeover key
      was operative.

PMID- 16811464
TI  - The role of reinforcement in controlling sequential IRT dependencies.
AB  - Sequential dependencies were investigated with two rats in a mixed and in a
      tandem differential-reinforcement-of-low-rate-responding schedule. In each
      schedule, 5-sec and 15-sec components were presented in fixed alternation. In the
      mixed schedule, a 5-sec interresponse time followed a 15-sec interresponse time
      and a 15-sec interresponse time followed a 5-sec interresponse time in
      predictable sequence. The correlation between prior and subsequent interresponse
      times, however, existed only when the prior interresponse time resulted in
      reinforcement. In the tandem schedule, an interresponse time greater than 5 sec
      in the differential-reinforcement-of-low-rate 5-sec component was not associated
      directly with reinforcement. One subject demonstrated sequential response
      patterns similar to those noted in the mixed schedule, even though the prior 5
      sec interresponse time was not reinforced in the tandem schedule. The results
      indicate that the prior interresponse time length alone is not sufficient to
      influence the subsequent interresponse time length. Implications are, however,
      that a temporal response pattern arises when an interresponse interacts with
      schedule contingencies to control the interreinforcement interval.

PMID- 16811465
TI  - A cartridge for running long variable-interval tapes.

PMID- 16811466
TI  - Fractional punishment of fixed-ratio performance.
AB  - Key-peck responses of pigeons under a fixed-rate 60 (Exp. I) or fixed-ratio 99
      (Exp. II) schedule of positive reinforcement were punished by response-dependent
      electric shock during a segment of the ratio. The punishing stimulus was
      scheduled in one of three locations: the first third of the ratio, the middle
      third, or the final third. At high shock levels, the different loci of punishment
      differentially affected the typical fixed-ratio performance pattern. Post
      reinforcement pauses were lengthened by all punishment conditions but to a
      greater degree when the responses in initial third of the ratio were punished.
      Disruption of responses before the punished segment of the ratio was a
      conspicuous feature of the performances when the middle or final third of the
      ratio was punished. Two of the punishment conditions produced similar effects on
      both fixed-ratio baselines but punishing the final third of the ratio suppressed
      the punished responses of the ratio only with the fixed-ratio 99 schedule.
      General effects of all punishment conditions included consistent intra-session
      recoveries of partially suppressed performances, the rapid recovery of the FR
      performances after the punishment dependency was removed after complete
      suppression, and the facilitation of overall and/or local response rates of most
      subjects by low-intensity shock.

PMID- 16811467
TI  - A simple mechanical uptake roller for cumulative recorder data.

PMID- 16811468
TI  - The effect of punishment shock intensity upon responding under multiple
      schedules.
AB  - In the first of two experiments, responses of two pigeons were maintained by
      multiple variable-interval, variable-ratio schedules of food reinforcement.
      Concurrent punishment was introduced, which consisted of a brief electric shock
      after each tenth response. The initial punishment intensities had no lasting
      effect upon responding. Then, as shock intensity increased, variable-ratio
      response rates were suppressed more quickly than variable-interval response
      rates. When shock intensity decreased, variable-interval responding recovered
      more quickly, but the rates under both schedules eventually returned to their pre
      punishment levels. In the second experiment, the following conditions were
      studied in three additional pigeons: (1) With each shock intensity in effect for
      a number of sessions, punishment shock intensity was gradually increased and
      decreased and responding was maintained by multiple variable-ratio, fixed-ratio
      schedules of food reinforcement; (2) Changes in punishment shock intensity as
      described above with responding maintained by either a variable-ratio or a fixed
      ratio schedule, which were presented on alternate days; (3) Session-to-session
      changes in shock intensity with responding maintained by multiple variable-ratio,
      fixed-ratio schedules. Responding under the two schedules was suppressed to
      approximately the same extent by a particular shock intensity. Also, post
      reinforcement pauses under the fixed-ratio schedule increased as response
      suppression increased.

PMID- 16811469
TI  - The response-shock-shock-shock interval and unsignalled avoidance in goldfish.
AB  - Goldfish were trained to swim back and forth in a shuttle tank to avoid
      unsignalled shocks. The response-shock interval and the shock-shock interval were
      always of equal duration; both were either 15, 30, 45, or 60 sec. Response rates
      varied inversely with response-shock-shock-shock interval duration, as has been
      found with rats. Percentage of shocks avoided was somewhat lower at the 15 sec
      response-shock-shock-shock interval, but otherwise did not vary systematically
      with changes in the interval. As the response-shock-shock-shock interval
      increased, the fish made increasingly more responses than necessary to avoid all
      shocks. Interresponse-time distributions showed that response probability rose to
      a maximum at about 15 to 25 sec after a response, regardless of the response
      shock-shock-shock interval. Thus, at the longer intervals the fish were
      responding too early in the response-shock-shock-shock interval to minimize
      response rates.

PMID- 16811470
TI  - Observational learning in monkeys.
AB  - Observer monkeys were housed next to demonstrator monkeys that were conditioned
      to respond on a multiple reinforcement schedule whose components were fixed-ratio
      32, variable-interval 3-min, and extinction 5-min followed by an additional 30
      sec of extinction during which every response started a new 30-sec interval.
      After observational periods from 113 to 210 hr long, during which observers could
      not perform the response and were given no extrinsic reinforcers, their first
      response latencies to fixed ratio and variable interval were as short as the
      demonstrators; and their rates of responding were well above pre-observational
      baseline levels. About 8 hr later, a temporal pattern of responding appropriate
      to the multiple schedule emerged, including non-emission of responses during
      extinction. Controls lacking the chance to observe did not develop typically
      patterned responding after 60 hr in one case and, in two other cases, after 80 hr
      during which, on two occasions, every one of 50 responses was reinforced. In a
      second experiment, the stimulus lights associated with fixed ratio and variable
      interval were presented simultaneously. Subjects chose one of the schedules by
      responding to one of the levers beneath the lights. All subjects initially chose
      fixed ratio. Seeing the demonstrators switch to variable interval, due to
      increases in the fixed-ratio requirement, had no effect upon observers, which
      continued to choose fixed ratio.

PMID- 16811471
TI  - Operant conditioning in redwinged blackbirds.
AB  - An operant conditioning technique for use with passerine birds is described. Two
      redwinged blackbirds were successfully conditioned to perch-hop for food
      reinforcement. Continuous reinforcement and fixed-ratio schedules involving
      substantial ratio requirements were used to maintain this response. The behavior
      of the two redwinged blackbirds was comparable to that of more conventional
      organisms working on similar schedules of reinforcement.

PMID- 16811472
TI  - Positive reinforcement and suppression from the same occurrence of the
      unconditioned stimulus in a positive conditioned suppression procedure.
AB  - Responding of rats was maintained on a variable-interval schedule of food
      reinforcement. The same response also produced a blinking light followed by
      electrical brain stimulation according to a fixed-interval schedule. This
      conjoint schedule produced two behavioral changes. First, instead of a steady
      rate of responding throughout the session, which would be characteristic of the
      variable interval food schedule alone, responding between occurrences of the
      light-brain stimulation pairings became positively accelerated and thus was more
      characteristic of the fixed-interval schedule of these pairings. Second, food
      responding was suppressed during the light that preceded brain stimulation. These
      results indicate that positive reinforcement and suppression resulted from the
      same occurrence of the light-brain stimulation combination. This finding suggests
      that stimuli such as conditioned reinforcers that precede an unconditioned
      reinforcer may have a suppressive effect upon responding in their presence that
      is being maintained by another reinforcer.

PMID- 16811473
TI  - Negative reinforcement without shock reduction.
AB  - Stable lever-press responding in rats was reliably produced and maintained by a
      procedure in which responses could delay shocks without affecting overall shock
      frequency. Responding was not maintained when the delay-of-shock involved an
      increase in overall shock frequency.

PMID- 16811474
TI  - Effects of rate of reinforcement-time upon concurrent operant performance.
AB  - Three experiments were conducted to investigate the theoretical reduction of rate
      and duration of reinforcement to their product, rate of reinforcement-time, under
      concurrent chain schedules. In Exp. I, rate of reinforcement-time was varied by
      varying rate of reinforcement delivery, holding duration of reinforcement
      availability constant; in Exp. II, rate of reinforcement-time was varied by
      holding rate of reinforcement delivery constant and varying duration of
      reinforcement availability; in Exp. III, rate of reinforcement-time was held
      constant by varying both rate and duration of reinforcement simultaneously and
      inversely. For all three experiments, both relative rate of responding and
      relative time spent in the initial link were found to match approximately the
      relative rate of reinforcement-time arranged in the terminal link. These data
      were interpreted as support for the notion that rate and duration of
      reinforcement may be functionally equivalent and reducible to a single variable,
      rate of reinforcement-time.

PMID- 16811475
TI  - Time limits for completing fixed ratios.
AB  - Two experiments investigated how the addition of time limits affected fixed-ratio
      behavior. In Exp. 1, pigeons obtained food only if they completed the ratio
      within a specified time after the end of the preceding ratio. In Exp. 2, they
      obtained food only if they took longer than a specified time. Failures to meet
      the time criteria produced brief timeouts. The times taken depended on the
      requirements in both experiments. In Exp. 1, progressively briefer time criteria
      resulted in faster ratios, and in Exp. 2, longer time criteria increased the time
      taken in each ratio. The pigeon's sensitivity to the temporal variable, a
      property of the entire period extending from the first opportunity to respond to
      the end of the ratio, indicated that performance involved a behavioral unit
      encompassing both the post-reinforcement pause and the responses comprising the
      ratio.

PMID- 16811476
TI  - Fixed-interval stimulus control.
AB  - Pigeons were exposed to three stimuli simultaneously, with responses to one of
      them, the positive stimulus, followed by food presented according to a fixed
      interval schedule (FI 2-min, FI 4-min, FI 8-min, or FI 16-min). Over 90% of the
      total responses emitted were to the positive stimulus within a few sessions. When
      the birds were then studied under each of four fixed intervals, responding
      continued to be confined primarily to the same stimulus independent of interval
      size. In subsequent conditions, the three stimuli changed positions after each
      quarter of the interval. If the position changes did not require a response,
      response rate and the percentage of responses occurring to the positive stimulus
      decreased. If the changes did depend on a response, the complete interval
      appeared to be divided into four smaller intervals with a pause and then
      positively accelerated responding following each position change. Position
      changes produced by a response to any stimulus decreased control by the positive
      stimulus, and changes produced only by a response to it increased the percentage
      of responses made to that stimulus. All of the data suggested that the stimulus
      conditions contiguous with reinforcement controlled behavior.

PMID- 16811477
TI  - Independently delivered food decelerates fixed-ratio rates.
AB  - Following fixed-ratio baselines, the independent delivery of reinforcers was
      scheduled alone or concomitant with the fixed-ratio schedule for all subjects.
      Systematic manipulations of either the interreinforcement interval or the ratio
      size were also made during concomitant schedules. Response rates during the
      independent delivery of reinforcers did not decelerate until the subjects had
      been exposed for 50 or more sessions. Rates decelerated after a few sessions when
      the interreinforcement intervals were less than half of the original value and
      scheduled along with the ratio dependency. When both schedules were available,
      reductions in the ratio size resulted in slight deceleration of response rate
      when compared with the level of deceleration yielded by reductions in the
      independent reinforcement intervals.

PMID- 16811478
TI  - Effects of a pre-shock stimulus on temporal control of behavior.
AB  - Rats were exposed to a situation in which a response on lever B was followed by
      reinforcement if a preceding response on lever A had been made at least 5, 10, or
      15 sec before. The effects of signalled unavoidable shock were studied on the
      behavior maintained by this procedure. All rats made fewer A-to-B sequences
      during the periods of pre-shock stimulus. In addition, when the A-to-B delay was
      10 or 15 sec, the distribution of A-to-B times changed, there being more shorter
      intervals. However, for animals where the A-to-B delay was 5 sec, the
      distribution of A-to-B times was not changed during the pre-shock stimulus. In
      all cases, there was an increased proportion of inappropriate B responses (i.e.,
      with no preceding A response) during the pre-shock stimulus; this was most marked
      with animals exposed to a 15-sec A-to-B delay.

PMID- 16811479
TI  - The effect of shock intensity upon responding under a multiple-avoidance
      schedule.
AB  - The effect of two shock intensities (1.00 and 2.00 mA) were studied in the
      acquisition, maintenance, and extinction of unsignalled avoidance by albino rats.
      Single and multiple avoidance schedules were employed, with shock intensity being
      the principal condition that differed between schedule components. The higher
      shock intensity was generally more effective in producing avoidance. Higher
      response rates and lower shock rates were observed under high-intensity shock
      when performance stabilized. When the multiple schedule was introduced, the six
      rats trained under a single shock intensity all showed poorer performance under
      the new shock intensity, whether it was higher or lower than the training
      intensity. Performance under the original shock intensity did not change
      substantially with the introduction of a different shock intensity in the other
      multiple schedule component. Performance under the new shock intensity showed
      gradual improvement with continued exposure to it. All of the rats showed
      persistent "warm-up", receiving approximately 40% of the total session shocks in
      the first one-sixth of the session. The degree of warm-up was unrelated to
      avoidance shock intensity.

PMID- 16811480
TI  - The effect of a pre-shock signal on a free-operant avoidance response.
AB  - After 25 free-operant avoidance training sessions, a 1-min signal followed by a
      brief shock was presented on the average of once every 4 min. During the signal,
      the avoidance schedule was suspended (20 sessions). Response rates during the
      signal were markedly reduced. Shock rates during non-signalled periods increased.
      Fifteen additional sessions were given during which the signal was presented
      without shock. Response rates during signalled periods were greater than
      previously observed during signalled periods, indicating that signalled shock had
      suppressive control over a previously acquired avoidance response rate.

PMID- 16811481
TI  - Auditory frequency generalization in the goldfish (Carassius auratus).
AB  - Auditory frequency generalization in the goldfish was studied at five points
      within the best hearing range through the use of classical respiratory
      conditioning. Each experimental group received single-stimulus conditioning
      sessions at one of five stimulus frequencies (100, 200, 400, 800, and 1600 Hz),
      and were subsequently tested for generalization at eight neighboring frequencies.
      All stimuli were presented 30 db above absolute threshold. Significant
      generalization decrements were found for all subjects. For the subjects
      conditioned in the range between 100 and 800 Hz, a nearly complete failure to
      generalize was found at one octave above and below the training frequency. The
      subjects conditioned at 1600 Hz produced relatively more flat gradients between
      900 and 2000 Hz. The widths of the generalization gradients, expressed in Hz,
      increased as a power function of frequency with a slope greater than one.

PMID- 16811483
TI  - Summation of punishment suppression.
AB  - In two experiments, eight rats were trained to lever press with food on a
      variable-interval schedule. Bar pressing produced shock on a variable-interval
      schedule in the presence of two independently presented stimuli, a light and a
      tone. Two rats in each experiment received alternative presentations of the light
      and the tone and were consequently always in the presence of a stimulus that
      signalled variable-interval punishment. The other two rats in each experiment
      were treated similarly except that they received periods in which neither light
      nor tone was present. During these periods, bar pressing was not punished. The
      two stimuli that signalled punishment were then presented simultaneously to
      evaluate the effect of stimulus compounding on response suppression. The subjects
      trained without punishment-free periods did not show summation to the compound
      stimulus; the subjects trained with punishment-free periods showed summation of
      suppression. The major difference between the two experiments was the longer mean
      interval of variable-interval punishment used in the second experiment. This
      manipulation made the summation effect more resistant to extinction and thus
      increased its magnitude.

PMID- 16811482
TI  - Inhibition and the stimulus control of operant behavior.
AB  - A variety of methods, definitions, and theoretical notions that have been used in
      the study of inhibitory stimulus control were reviewed and evaluated. Preliminary
      data from several new operant methods were also described. It was proposed that
      future workers distinguish clearly between two forms of inhibitory control: (a)
      the learned power of a specific stimulus to reduce behavior, and (b) a
      dimensional effect, in which responding increases as values progressively more
      distant from the value of that specific stimulus along some dimension are
      presented (generalization gradient). Conclusions from several important recent
      studies were shown to be strongly dependent on the individual experimenter's
      criterion for deciding when a stimulus is inhibitory. The concept of inhibition
      seems a very valuable one for the field of operant behavior, and it deserves more
      attention than it has received in the past.

PMID- 16811484
TI  - A rapid automatic technique for generating operant key-press behavior in rats.
AB  - Experimentally naive rats were trained to key press on a fixed-ratio 10 schedule
      of food reinforcement by a completely automatic procedure within a single, 1-hr
      session. Control procedures demonstrated that the resulting behavior was an
      operant, under control of the schedule of reinforcement and the specified
      reinforcing stimulus (food). A simple, combination food-tray operandum, also
      described, was used as the basis for the training technique.

PMID- 16811485
TI  - The effects of brief stimuli presented under a multiple schedule of second-order
      schedules.
AB  - The effects of briefly presented stimuli paired or not paired with food
      reinforcement were investigated in the pigeon on a multiple schedule containing
      second-order schedules. A stimulus paired with food reinforcement was presented
      on a variable-interval schedule in one unit of the multiple schedule and either a
      stimulus not paired with food reinforcement or no stimuli were scheduled in the
      other unit. Response rates were highest when behavior was followed by the food
      paired stimulus. Presentation of the food-paired stimulus at completion of each 1
      min variable-interval component maintained a steady rate of responding between
      consecutive food presentations. Pausing following food reinforcement was greatest
      in the second-order schedule not containing the paired stimulus. Reversing the
      stimulus pairings led to a reversal of the relative response rates and patterns
      of responding for each stimulus.

PMID- 16811486
TI  - A model for choice in simple concurrent and concurrent-chains schedules.
AB  - Pigeons' responses in the presence of two concurrently available (initial-link)
      stimuli produced one of two different (terminal-link) stimuli. Entrance into the
      mutually exclusive terminal links was arranged by different and independent
      variable-interval schedules for each key, while responses during the mutually
      exclusive terminal-link stimuli produced a single food reinforcement according to
      indentical and independent variable-interval schedules. The pigeons emitted more
      initial-link responses on the key with the shorter average interreinforcement
      interval in the initial link. This difference in initial-link response rates
      varied directly with the difference between the average inter-reinforcement
      intervals of the initial-link schedules and decreased when the initial-link
      schedule with the longer average interreinforcement interval was followed by
      several consecutive food reinforcements on the variable-interval schedule in the
      terminal link on that key. These results are incompatible with previous
      formulations of choice behavior with the concurrent-chains procedure. A modified
      formulation with a multiplier for the overall rate of primary reinforcement
      obtained on each key provides a better description of choice. In addition, the
      new formulation applies to behavior in simple (concurrent) choice situations, an
      advantage not achieved by previous formulations.

PMID- 16811487
TI  - An apparatus for delivery of electroconvulsive shock without situational change.

PMID- 16811488
TI  - Sequence schedules of reinforcement.
AB  - The performance of pigeons was studied under a second-order schedule composed of
      fixed-interval components, each of which was associated with a different
      discriminative stimulus, the stimuli occurring in a fixed order. In one
      condition, food presentation followed the completion of the fourth component.
      This was designated a fixed-ratio sequence schedule. In another condition,
      responses in the first component completed after a fixed time were reinforced.
      This was designated a fixed-interval sequence schedule. Although the stimulus
      order and maximum reinforcement frequency were identical under the two schedules,
      considerably more responding occurred under the fixed-interval sequence schedule
      in all components. Relatively few food presentations occurred after responding
      during any but the terminal components of the fixed-interval sequence schedule, a
      feature independent of the parameter values investigated. In addition, while a
      pattern of increased responding between food presentations prevailed under both
      schedules, under the fixed-interval sequence schedule the rate in the terminal
      component was frequently less than in the penultimate component. The fixed
      interval sequence schedule appeared to have several properties of simple fixed
      interval schedules.

PMID- 16811489
TI  - Facilitation of food-reinforced responding by a signal for response-independent
      food.
AB  - Five pigeons whose key pecking was maintained by 4-sec access to grain on a
      variable-interval 2-min schedule received Pavlovian differential conditioning
      trials superimposed upon the instrumental baseline. The conditioned stimuli were
      changes in the stimulus on the key from white to red, or to a white horizontal
      line against a dark background. The positive conditioned stimulus was 20 sec
      long, and was followed immediately by 8-sec access to grain. The negative
      conditioned stimulus, also 20 sec long, was never paired with response
      independent food. All pigeons responded more rapidly in the presence of the
      positive conditioned stimulus than in the presence of the negative one. The
      positive conditioned stimulus produced an increase in response rate over the pre
      conditioned stimulus period. The negative conditioned stimulus had no marked
      effect upon response rate. When the roles of the positive and negative stimuli
      were reversed, and the duration of the response-independent reinforcement was
      reduced to 4 sec, the new positive conditioned stimulus came to facilitate
      responding, and the new negative conditioned stimulus no longer produced
      facilitation. A second discrimination reversal produced similar outcomes. When a
      third reversal was initiated, and the duration of response-independent
      reinforcement was reduced to 2 sec, the difference between the effects of the
      positive and negative stimuli diminished.

PMID- 16811490
TI  - A restraint system for chronic study of the baboon.

PMID- 16811491
TI  - Color-naming functions for the pigeon.
AB  - Six pigeons were trained to match wavelengths in a three-key matching-to-sample
      paradigm. Test trials were occasionally presented, where probe wavelengths
      appeared on the center key and choices were made to the training stimuli
      presented on the side keys. Color naming functions were obtained by plotting the
      percentage of test trials that each training stimulus wavelength was chosen for
      each center key probe wavelength. The wavelength where the functions intersected
      was interpreted as a transition point between pigeon hues. Three experiments
      employed different wavelengths as training stimuli. The first two experiments
      demonstrated that the intersection of the color-naming functions occurred in all
      cases at 540 nm and 595 nm. The third experiment employed 540 nm and 595 nm as
      two of the three training stimuli, and the relatively slow acquisition, together
      with the resulting color-naming functions, supported the proposition that 540 nm
      and 595 nm may be transition point wavelengths between pigeon hues.

PMID- 16811492
TI  - Peak shift in concurrent schedules.
AB  - Pigeons were exposed to two keys, a main key and a changeover key. Initially non
      differential training was given in which pecking the main key was reinforced on a
      variable-interval 2-min schedule when the key displayed the first stimulus, a
      black line on a blue background, and was reinforced on an identical but
      independent variable-interval 2-min schedule when the key displayed a plain blue
      stimulus. Later, differential training was given in which pecking the main key
      was reinforced on a variable-interval 2-min schedule when the first stimulus was
      displayed; and was reinforced on a variable-interval 10-min schedule when a
      second stimulus, a black line of another orientation on a blue background, was
      displayed. During non-differential and differential training, each peck on the
      changeover key changed the stimulus on the main key. Generalization tests were
      given before and after the differential training. These consisted of
      presentations on the main key of seven orientations of the black line on the blue
      background, including the first and second stimuli, with no reinforcements being
      given. Changeover-key pecks changed the stimuli on the main key. Generalization
      gradients were obtained using three measures: time spent, responses, and response
      rate in the presence of each test stimulus. Typically, maximum values on these
      measures occurred to stimuli away from the first in a direction opposite the
      second stimulus, and minimum values occurred to stimuli away from the second in a
      direction opposite the first.

PMID- 16811493
TI  - Collateral behavior of the pigeon during conditioned suppression of key pecking.
AB  - Ethological recording procedures measured collateral behavior in pigeons whose
      key-pecking performance was suppressed during a tone that ended with unavoidable
      electric shock. Independent recordings of gross behavior were made by two
      observers throughout 60-sec intervals immediately before, during, and after tone
      presentation. Results indicated significant reductions in the frequency of
      collateral movements and an increase in the time between successive movements
      during tone presentations. These effects were observed in all subjects, despite
      differences in the sequential patterns of behavior. Only partial recovery of the
      behavior evidenced before tone presentation was found during a 60-sec interval
      following shock. It was concluded that conditioned suppression procedures caused
      the bird to "freeze" during tone presentation and in this fashion produced a
      general inhibitory effect on ongoing overt activity, including key pecking.

PMID- 16811494
TI  - An operant feeding device for sheep.

PMID- 16811495
TI  - Color alternation learning in the pigeon under fixed-ratio schedules of
      reinforcement.
AB  - Pigeons were trained on a non-spatial delayed alternation task in which the
      correct stimulus was that color not responded to on the preceding trial. Subjects
      required to emit either 15 or 30 pecks to the correct stimulus within a trial
      learned the task, those required to emit only one or five pecks did not. Also,
      alternation was learned more easily after an incorrect than after a correct
      trial. Later experiments showed that a minimum fixed-ratio value was required for
      successful color alternation to occur, even though no fixed-ratio requirement was
      necessary when a position cue was available. The mechanism of the fixed-ratio
      effects derived from the pigeons' tendency to repeat their response in the
      presence of the color reinforced on the last trial. Whereas subjects trained on
      larger fixed-ratios corrected this error tendency within a trial, subjects
      trained on smaller fixed ratios did not.

PMID- 16811496
TI  - Effects of long-term shock and associated stimuli on aggressive and manual
      responses.
AB  - Squirrel monkeys were exposed to response-independent, fixed-frequency shock that
      produced biting attack upon a pneumatic hose. Attacks decreased within and across
      sessions at low intensities and high frequencies of shock, but increased within
      and across sessions at higher intensities and lower shock frequencies. Stimuli
      paired with shock, when presented alone, came to produce biting, and stimuli
      correlated with shock parameters that produced increases in responding within
      sessions produced similar increases when presented alone. Further experiments
      showed that continuing exposure to shock also produced lever pressing or chain
      pulling, with longer shock exposure again producing higher response rates.
      Whereas biting generally decreased throughout the intershock interval, manual
      responding generally increased as shock time approached, but immediately before
      shock was often suppressed. Following shock, biting attack predominated over
      manual behavior. The results suggest a possible explanation for the extreme
      resistance of avoidance behavior to extinction, and may also partially explain
      the persistence of responding during schedules of response-produced shock.
      Relationships of the present findings to naturalistic observations of relations
      between fleeing, freezing, and fighting performances are discussed.

PMID- 16811497
TI  - Control of concurrent avoidance and appetitive behaviors by an indicator of shock
      proximity.
AB  - Two monkeys were exposed to concurrent schedules in which every fifth response on
      one lever had the dual consequences of delivering food and stepping a 20-step
      light counter upward; responses on a second lever stepped the light downward. By
      responding appropriately on each lever, a ration of food could be obtained
      without exposure to a brief shock that occurred when the counter reached the
      twentieth step. Behavioral patterns of light-counter control were analyzed when
      the monkeys were handicapped by several types of discontinuities in the 20-step
      counter: (1) different sets of four consecutive lights inoperative, (2) the upper
      or lower 10 steps inoperative, and (3) all lights inoperative. Generally, the
      monkeys maintained the light in the upper five steps of the 20-step light counter
      if the lights immediately preceding the shock position were functional. However,
      when these counter positions were inoperative, subjects maintained the counter
      around the highest operative position. With all positions of the light counter
      inoperative, no systematic pattern of responding on the food and avoidance levers
      occurred.

PMID- 16811498
TI  - Second-order optional avoidance as a function of fixed-ratio requirements.
AB  - Two rhesus monkeys responded on a fixed-ratio schedule in Stimulus 1 (blue light)
      to avoid the onset of Stimulus 2 (green light). Failure to avoid Stimulus 2
      required a second fixed-ratio performance to avoid Stimulus 3 (red light) in the
      presence of which unavoidable shock occurred. Relative frequencies of avoidance
      performance in the blue light and in the green light were inversely related to
      the ratio requirement under each stimulus condition. Both differential response
      cost and avoidance-failure probability factors were related to the observed
      changes.

PMID- 16811499
TI  - Measuring flicker thresholds in the budgerigar.
AB  - A method of measuring thresholds in animals is described and illustrated in the
      case of flicker fusion in the budgerigar. After training with reinforcement for
      pecking at a high-frequency light (115 Hz) and nonreinforcement for pecking at a
      low-frequency light (20 Hz), subjects were given threshold trials and
      reinforcement trials mixed randomly in equal number. In threshold trials (no
      reinforcement), the target began flashing at 115 Hz and decreased in flash rate
      with each peck until the subject stopped responding. During reinforcement trials,
      the target continued to flash at 115 Hz, and responses were reinforced on a
      variable-ratio schedule. Flicker thresholds obtained from two birds showed a
      linear relation to the logarithm of intensity in accordance with the Ferry-Porter
      law.

PMID- 16811500
TI  - Elicitation and punishment of intraspecies aggression by the same stimulus.
AB  - Fighting responses were elicited in pairs of rats by shocks over a period of 46
      days. During certain blocks of these days, "punishing" shocks were made
      contingent on the shock-elicited fights. Fighting frequency was reduced as a
      direct function of the intensity of the contingent shocks. Fighting frequency
      recovered completely when contingent shocks were removed.

PMID- 16811501
TI  - Automatic magazine and bar-press training in the rat.

PMID- 16811502
TI  - Observing responses and informative stimuli.
AB  - Pigeons were trained on a trial procedure. A trial began with the illumination of
      a pecking key by a white light. After a fixed interval, a key peck could turn the
      key to one of two equi-probable colors and produce a delayed trial outcome-an
      equi-probable occurrence of either reinforcement or nonreinforcement. After a
      trial, the key turned dark and the trial ended. The response could be made into
      an observing response by correlating the key colors with the outcomes. Response
      rates in the fixed interval then increased to a level greater than when the
      colors and outcomes were uncorrelated. In another phase, the response produced
      only the colors. The trial outcomes occurred some seconds after the fixed
      interval without a response being required. Correlating the colors with the
      outcomes again increased response rates. In a second experiment, a further
      condition was added in which reinforcement was the outcome on every trial.
      Response rates were lower than when there were equi-probable reinforcement and
      nonreinforcement outcomes with correlated colors, and about the same as when
      there were equi-probable outcomes with uncorrelated colors. The results suggest
      that stimuli providing information about the probability of reinforcement are
      themselves reinforcing.

PMID- 16811503
TI  - Matching to relative reinforcement frequency in multiple schedules with a short
      component duration.
AB  - Three pigeons performed on two-component multiple variable-interval variable
      interval schedules of reinforcement. There were two independent variables:
      component duration and the relative frequency of reinforcement in a component.
      The component duration, which was always the same in both components, was varied
      over experimental conditions from 2 to 180 sec. Over these conditions, the
      relative frequency of reinforcement in a component was either 0.2 or 0.8 (+/
      0.03). As the component duration was shortened, the relative frequency of
      responding in a component approached a value equal to the relative frequency of
      reinforcement in that component. When the relative frequency of reinforcement was
      varied over conditions in which the component duration was fixed at 5 sec, the
      relative frequency of responding in a component closely approximated the relative
      frequency of reinforcement in that component. That is, the familiar matching
      relationship, obtained previously only with concurrent schedules, was obtained in
      multiple schedules with a short component duration.

PMID- 16811504
TI  - Concurrent schedules of response-independent reinforcement: duration of a
      reinforcing stimulus.
AB  - Presentations of grain to three pigeons were determined by two response
      independent schedules. Interpresentation intervals varied with a mean interval of
      1.5 min for each schedule. Both were concurrently operative, but grain was
      presented by one only when the chamber was illuminated with blue light and by the
      other only during amber illumination. A response on a white key, the only key in
      the chamber, alternated the stimulus conditions and the effective schedule. Grain
      presentation durations associated with the illumination conditions were varied
      from 1.5 to 4.5 sec. The proportion of the total session time spent in an
      illumination condition closely approximated the relative grain presentation
      duration provided in that illumination. For two of the birds, the proportion of
      the total number of grain presentations obtained in an illumination condition was
      an increasng function of the presentation duration in that illumination.

PMID- 16811505
TI  - Sequential patterns in post-reinforcement pauses on fixed-interval schedules of
      food.
AB  - Responding by one pigeon was reinforced with food on fixed-interval schedules of
      30, 60, and 300 sec duration. A second pigeon was studied under fixed-interval
      durations of 60 and 300 sec. For both birds, the average post-reinforcement pause
      was one-half the duration of the fixed interval. Autocorrelation coefficients
      revealed first-order sequential dependencies in series of post-reinforcement
      pauses. On the 300-sec fixed-interval schedule, successive post-reinforcement
      tended to alternate between long and short durations. At the shorter fixed
      interval durations there was less evidence of alternation sequences. A second
      experiment was conducted to determine if the time intervals between the first
      response after reinforcement and the next reinforcement (the work periods) were
      responsible for the alternation patterns in the series of post-reinforcement
      pauses. To evaluate the role of the work period, several procedures were used to
      modify the work period from that obtained on the fixed-interval 300-sec schedule.
      Adding a schedule to the fixed-interval schedule that set the minimum amount of
      time that could elapse between the first response after reinforcement and the
      next reinforcement eliminated the alternation pattern. Control schedules
      indicated that the elimination of alternation patterns resulted from constraints
      on the work period per se and not from confounded changes in the
      interreinforcement intervals.

PMID- 16811506
TI  - Color mixing with Kodak Wratten filters.

PMID- 16811507
TI  - Response rate under varying frequency of non-contingent reinforcement.
AB  - Two White Carneaux hen pigeons were exposed to a 60-sec random-interval baseline
      procedure. Six different exteroceptive stimuli were successively correlated,
      within a single session, with blocks of 10 reinforcement presentations. Following
      this training, a non-contingent reinforcement procedure was instated with inter
      reinforcement intervals of 5, 15, 30, 60, 120, and 240 sec. Within a single
      session, each non-contingent frequency was correlated with one of the previously
      presented discriminative stimuli. After an initial increase in the rate of
      responding as the result of a high density of non-contingent reinforcements, the
      rate declined as exposure to each non-contingent frequency was prolonged.

PMID- 16811508
TI  - Differential reinforcement of other behavior (DRO): a yoked-control comparison.
AB  - After training to press a lever on a variable-interval 30-sec schedule, one group
      of rats was shifted to a differential-reinforcement-of-other-behavior 10-sec
      schedule, while a second group was shifted to a noncontingent yoked-control
      schedule that provided the same frequency and distribution of reinforcement.
      Then, both groups were extensively retrained on the variable-interval schedule,
      after which the first group was shifted to a series of differential-reinforcement
      of-other-behavior 30-sec sessions alternating daily with variable-interval 30-sec
      sessions, while the second group was treated like the first on variable-interval
      days and yoked with the first as before on differential-reinforcement-of-other
      behavior days. In both phases, response-decrement was more rapid and more marked
      in the differential-reinforcement-of-other-behavior animals than in the controls.
      The difference was due, at least in large measure, to sustainment of response in
      the control animals by adventitious reinforcement. All the differential
      reinforcement-of-other-behavior animals developed "other" behavior-the same
      distinctive pattern of waiting at the foodcup-but there was no direct evidence
      that it contributed in any way to the decrement in lever pressing.

PMID- 16811509
TI  - Positive conditioned suppression: effects of CS duration.
AB  - During a brief conditioned stimulus (15 or 30 sec) that terminated with the
      response-independent delivery of banana pellets, operant responding reinforced by
      other food pellets according to a variable-interval schedule of reinforcement was
      suppressed in the squirrel monkey. Conditioned stimuli of longer duration (1, 2,
      and 3 min) did not reliably affect the rate of operant performance. Brief
      conditioned stimuli generated homogeneous response patterns of nearly complete
      suppression. Increasing the CS duration did not enhance responding, as previously
      reported, but led to alternate bursting and pausing, which suggested a loss of
      control by the conditioned stimulus. The results suggest that the magnitude of
      "positive" or "negative" conditioned suppression reflects the strength of the
      classical conditioning process.

PMID- 16811510
TI  - A convenient method for physical storage of cumulative records.

PMID- 16811511
TI  - On the tautology of the matching law.
AB  - The generalized matching law, that organisms divide their time between
      alternatives in proportion to the value of the reinforcement consequent on the
      choice, is derivable from the assumption that an organism choosing between
      alternatives is under no constraints except those the contingencies of
      reinforcement impose. Hence, the law is not subject to empirical test. Its value
      lies in its simple codification of assumptions underlying choice experiments.

PMID- 16811512
TI  - Rate changes after unscheduled omission and presentation of reinforcement.
AB  - Changes in response rate similar to frustration effects were studied in a two
      lever situation. Responding on one lever on a fixed-interval schedule produced
      access to water for 5 sec and an exteroceptive stimulus. In the presence of this
      stimulus, responding on another lever on a fixed-interval schedule produced
      access to water for 5 sec and terminated the stimulus. Occasional omission of a
      previously scheduled reinforcer after responding on the first lever resulted
      consistently in increases in rate on the second lever during the immediately
      succeeding interval. In another procedure, occasional presentation of a
      previously unscheduled reinforcer after responding on the first lever resulted
      consistently in decreases in rate on the second lever during the immediately
      succeeding interval. Changes occurred after the first omissions or presentations
      and were about the same in magnitude as the procedure continued over several
      sessions. Typically, an increase or decrease in rate was maintained throughout an
      entire 100-sec interval. Changes in rate on the second lever of approximately the
      same magnitude also occurred when rate on the first lever was near-zero under a
      schedule that differentially reinforced behavior other than lever pressing.

PMID- 16811513
TI  - Reinforcement schedules: the role of responses preceding the one that produces
      the reinforcer.
AB  - In a two-key pigeon chamber, variable-interval reinforcement was scheduled for a
      specified number of pecks, emitted either on a single key or in a particular
      sequence on the two keys. Although the distribution of pecks between the two keys
      was affected by whether pecks were required on one or on both keys, the total
      pecks emitted was not; the change from a one-key to a two-key requirement simply
      moved some pecks from one key to the other. Thus, each peck preceding the one
      that produced the reinforcer contributed independently to the subsequent rate of
      responding; the contribution of a particular peck in the sequence was determined
      by the time between its emission and the delivery of the reinforcer (delay of
      reinforcement), and was identified by the proportion of pecks moved from one key
      to the other when the response requirement at that point in the sequence was
      moved from one key to the other.

PMID- 16811514
TI  - Contrast and induction in rats on multiple schedules.
AB  - Eight rats were trained on a variable-interval schedule in the presence of a
      light (Phase I). Responding was then extinguished in the presence of darkness
      that alternated with the light (Phase II). Reinforcement was then introduced in
      the presence of darkness (Phase III). Several rats were then returned to the
      condition of Phase II (Phase IV) and then to that of Phase III (Phase V). The
      responding of most rats showed clear behavioral contrast in Phase II-i.e., an
      increase in responding in the presence of the light. When, for three rats, Phase
      III was introduced early after the occurrence of positive contrast, either
      positive induction occurred, i.e., an increase in responding in the presence of
      the light, or there was little change. Negative contrast did not occur. It was
      further shown that positive contrast dissipates over time, thus replicating a
      result previously obtained with pigeons and that the positive induction effect
      seems also to dissipate over time. The introduction of reinforcement in the
      presence of darkness (Phases III and V) after the dissipation of positive
      contrast seemed to have little consistent effect.

PMID- 16811515
TI  - Percentage reinforcement of fixed-ratio and variable-interval performances.
AB  - Twenty to seventy per cent of the reinforcements scheduled for pigeons' fixed
      ratio 80 performances were replaced by a 4-sec timeout. Pauses after reinforced
      ratios were unchanged at 80% reinforcement, but were lengthened at lower
      reinforcement percentages. Pauses after nonreinforced ratios were shorter than
      post-reinforcement pauses. When 50% of the reinforcements arranged by a variable
      interval 60-sec schedule were replaced by a 4-sec timeout, pauses after
      reinforcement omission increased. Both frustrative nonreward and reinforcement
      aftereffects notions can explain the fixed-ratio results; neither easily explains
      the variable-interval data.

PMID- 16811516
TI  - Second-order schedules with fixed-ratio components: variation of component size.
AB  - Key pecking by pigeons was reinforced with food under second-order schedules with
      fixed-ratio units. A constant total number of key pecks was required for
      reinforcement under each condition, but the size and, inversely, number of fixed
      ratio components were varied. The total response requirement of 256 pecks was
      divided into fixed-ratio units of 128, 64, 32, 8, and 2 responses. A brief
      stimulus, which always preceded food reinforcement, was presented upon completion
      of each fixed-ratio unit. Under most conditions, the pattern of within-unit
      responding was typical of that under simple fixed-ratio schedules. Overall
      response rate was an inverted U-shaped function of component size. That is,
      response rates were highest under moderate sized units (fixed ratio 128 and 64).
      This relationship is consistent with previous determinations of rate as a
      function of fixed-ratio value for simple fixed-ratio schedules.

PMID- 16811517
TI  - Stimulus functions in some chained fixed-ratio schedules of reinforcement.
AB  - For two pigeons, behavior was compared in equivalent two-link chained and tandem
      schedules in which 100 responses were required for food reinforcement but the
      responses required in the two links of the chained schedule were varied over the
      values 2-98, 50-50, and 98-2. Initial pausing, response rate in each link, and
      the total time to complete each ratio were recorded. In chained components,
      initial-link pausing (for both birds) and total time to complete the ratio (for
      one bird) were generally shorter when the response requirement was 2-98 than when
      it was 50-50 or 98-2; for terminal-link pausing this relationship was reversed
      for both birds. There were also systematic changes in behavior in tandem
      components, and in the relationship between behavior in chained and tandem
      components. The results are discussed in terms of conditioned reinforcement.

PMID- 16811518
TI  - Avoidance of timeout from response-independent reinforcement.
AB  - Responses on a lever by rats postponed scheduled timeouts, or periods during
      which the delivery of response-independent food was withheld. The effects of a
      number of experimental variables were examined and the conclusions drawn are that
      the functional relations describing free-operant avoidance of timeout from
      response-independent reinforcement are similar to those for avoidance of electric
      shock and that both phenomena are sensitive to the same parametric manipulations.
      Results suggest that high frequency of food delivery in timein maintains a higher
      rate of timeout avoidance than low frequency. The evidence argues against an
      interpretation in terms of adventitious food-reinforcement of the timeout
      avoidance response. Finally, the effects of scheduling timeouts independently of
      responding and of omitting timeouts confirm the view that timeouts can be
      aversive and may act as punishment for responding.

PMID- 16811519
TI  - Effect of delay-interval illumination on matching behavior in the capuchin
      monkey.
AB  - Experiment 1 demonstrated that delayed matching-to-sample in the capuchin monkey
      was superior when the delay interval was spent in darkness rather than in
      moderate illumination. In contrast with previous studies in which the delayed
      matching ability of primates appeared limited to 60 sec or less, in the dark
      condition all subjects showed above-chance matching at a 120-sec delay interval.
      Experiment 2 verified that darkness during the delay interval can facilitate
      delayed matching and provided evidence that the effective variable was the
      illumination level of the delay interval rather than change in illumination,
      which in Exp. 1 was confounded with illumination level.

PMID- 16811520
TI  - Teaching serial position sequences to monkeys with a delayed matching-to-sample
      procedure.
AB  - Comparison was made of two methods for training monkeys to "observe" a two-member
      serial position sequence by pressing two consecutively lighted keys and then to
      "report" the sequence by pressing the same two keys in the same order but without
      the lights. A fading technique involving gradual elimination of brightness cues
      from "reporting" keys was found more effective than a no-fading procedure in
      which the cues remained bright during training and then were suddenly removed.
      Animals that failed to learn to report a new sequence with the no-fading
      procedure sometimes developed behavior incompatible with that desired. They made
      repeated and specific errors that prematurely terminated trials of the sequence
      to-be-learned, even though the correct key was cued by a bright light. They
      behaved appropriately, however, on succeeding trials of other sequences. Thus,
      the errors were followed by trials on which reinforcement occurred. Manipulation
      of this contingency indicated its importance in maintaining the stereotyped error
      patterns.

PMID- 16811521
TI  - Contrast and stimulus generalization following prolonged discrimination training.
AB  - Different groups of pigeons received discrimination training in which the
      reinforcement-associated and extinction-associated stimuli were respectively
      either (a) a line tilt vs a blank key, (b) a blank key vs a line tilt, or (c) two
      different line tilts. The high response rates that developed to the positive
      stimulus in all groups during discrimination learning were maintained over 64
      sessions of training. After these sessions, all subjects were tested for stimulus
      generalization along the line-tilt dimension. Gradients of relative (per cent)
      generalization around the stimulus associated with reinforcement (so-called
      excitatory gradients) and around the stimulus associated with extinction (so
      called inhibitory gradients) were as steep as they typically are after much
      briefer training periods. These results do not support several of Terrace's
      predictions on the basis of the hypothesis that emotional responses develop to
      the stimulus associated with extinction during discrimination learning with
      errors, but eventually dissipate after extended training.

PMID- 16811522
TI  - Testing for inhibitory stimulus control with S- superimposed on S+.
AB  - Pigeons learned a successive discrimination between a positive stimulus (red)
      correlated with a variable-interval 1-min reinforcement schedule and a negative
      stimulus (vertical line) correlated with either a variable-interval 5-min
      schedule or extinction. Transfer tests measured the rate of responding to the
      positive stimulus alone, to various orientations of the negative stimulus, and to
      the same line orientations superimposed on the positive stimulus. Although there
      were no gradients with minima at the training value for the negative stimulus
      dimension, the addition of the negative stimulus dimension to the positive
      stimulus always resulted in a lower response rate than that for the positive
      stimulus alone. The results demonstrate that an operational definition of
      inhibitory stimulus control that requires increased responding to stimuli more
      distant from a negative stimulus (along some dimension) is not always consistent
      with a definition that requires the suppression of responding in the presence of
      one stimulus, the positive stimulus, by the simultaneous presentation of another,
      the negative stimulus.

PMID- 16811523
TI  - Discrimination training and stimulus compounding: consideration of non
      reinforcement and response differentiation consequences of S.
AB  - In Exp. 1, four rats were trained on a two-component multiple schedule with tone
      and light each associated with different variable-interval schedules. Extinction
      in light-out no-tone, common to previous studies reporting additive summation to
      compounded discriminative stimuli, was omitted from training. In testing, the
      simultaneous presentation of tone and light controlled a response rate
      intermediate between that controlled by these stimuli presented singly. In Exp.
      2, animals were trained on three-ply multiple schedules. While tone and light
      were each associated with variable-interval schedules for both groups, light-out
      no-tone signalled extinction for one and differential-reinforcement-of-behavior
      other-than-bar-pressing for the other. This permitted response reduction during
      light-out no-tone to be viewed independently of non-reinforcement. Responding of
      both groups showed summation to tone plus light in testing, with the effect
      clearly larger for extinction-trained subjects. These experiments indicate that:
      (1) discrimination training afforded by extinction has been integral to additive
      summation previously reported, (2) response differentiation and non-reinforcement
      consequences of extinction training contribute to the magnitude of summation, and
      (3) summation and peak shift might be functionally related phenomena.

PMID- 16811524
TI  - A method of interfacing a small computer with psychological experiments.

PMID- 16811525
TI  - Taking and the disruption of cooperation.
AB  - Subjects could either cooperate or respond on a lower-paying individual task. In
      Exp. I and II, either subject could make a response that took $1.00 of the
      other's earnings whenever subjects chose to cooperate. The two experiments
      differed as to whether taking responses were effective continuously or
      intermittently. Both experiments showed that the opportunity to take disrupted
      cooperative behavior. Experiment III indicated that if taking was possible
      regardless of whether the subjects cooperated or responded on the individual
      task, subjects either cooperated or terminated the experiment.

PMID- 16811526
TI  - Operants.
AB  - The definition of an operant as a response class each of whose members possesses
      the property upon which reinforcement is contingent is not broad enough to cover
      the units that are supposed in Skinner's accounts of extinction, superstition,
      and transfer of learning. A broader definition is suggested. Finally, properties
      defining operants are discussed.

PMID- 16811527
TI  - Chained and tandem fixed-interval schedules of punishment.
AB  - Pigeons' key pecks were both punished with electric shock on four-component
      chained and tandem fixed-interval schedules and reinforced on a variable-interval
      schedule of food presentation. Pecking was suppressed less in the early
      components of the chained schedule than in the early components of the tandem
      schedule. Related multiple and mixed schedules of punishment were also presented;
      these schedules were identical to the chained and tandem schedules, respectively,
      except that components changed independently of responding. Similar effects were
      obtained, in that responding was suppressed in all components of the mixed
      schedule and only in the fourth component of the multiple schedule of punishment.
      The performances maintained on the chained and tandem schedules of punishment
      were generally symmetrical to those found in analogous chained and tandem
      schedules of food reinforcement.

PMID- 16811528
TI  - The relative aversiveness of signalled vs unsignalled avoidance.
AB  - Subjects avoided shock by pressing on one lever under an unsignalled condition,
      but by pressing a separate lever they changed the condition to signalled
      avoidance for 1-min periods. Signalled avoidance periods were identified by a
      correlated stimulus. All eight subjects responded to change the unsignalled
      schedule to a signalled one. Once contact with signalled avoidance was made,
      subjects continued responding to remain in that condition. Other tests showed
      that changeover responding was greater when the correlated stimulus was presented
      without the signal than when the signal was presented without the correlated
      stimulus. An analysis based upon shock and shock-free periods is presented.

PMID- 16811529
TI  - Response-dependent and response-independent timeout from an avoidance schedule.
AB  - While rats were responding in a single-lever apparatus to avoid electric shock, a
      signal was presented and followed by a 5-min timeout period when all shocks were
      omitted. For the response-dependent member of each yoked pair, the first response
      60 sec after onset of the pre-timeout signal terminated the signal and initiated
      timeout. The other, yoked animal was exposed to the same sequence except that
      signal termination and timeout onset were response independent. Under the
      response-dependent condition, response rates in the presence of the signal
      increased relative to baseline rates. Rate increases also occurred when timeout
      was response independent, but were of lesser magnitude and reliability.
      Subsequent reversal of the yoking arrangement produced stable and equivalent rate
      increases under both conditions. Other findings were that increased rates in the
      presence of the signal diminished when timeout was omitted but were maintained
      for a time on an avoidance-extinction baseline. In general, the results supported
      the conclusion of previous experiments that timeout from avoidance can serve as a
      positive reinforcer. The finding that response-independent presentation of
      timeout produced rate increases, particularly after a history with response
      dependent timeout, was interpreted in terms of adventitious reinforcement of
      previously established behavior.

PMID- 16811530
TI  - Non-spatial delayed alternation by the pigeon.
AB  - Pigeons were trained on a non-spatial delayed alternation task in which the color
      not pecked on the previous trial was correct. When varying delays were interposed
      between trials, alternation accuracy decreased as a function of delay, but
      remained greater than chance with a 45-sec delay. Successful alternation on the
      longer delays was accomplished without behavioral mediation of the delay
      intervals. Also, during initial testing when a position cue was available in
      addition to the color cue after incorrect trials, alternation accuracy was
      greater after a preceding incorrect trial than after a correct trial. When the
      position cue was removed, no differences occurred as a function of the outcome of
      the preceding trial.

PMID- 16811531
TI  - Fixed-ratio reinforcement of spaced responding.
AB  - Responses by rats were reinforced with food under a second-order schedule
      involving fixed-ratio reinforcement of temporally spaced responses. Requirements
      of 20, 8, and 3 responses were examined. The typical characteristic of spaced
      responding was maintained under the ratio schedules: interresponse time
      distributions were similar to those typically seen, and were not noticeably
      affected by the ratio value. Comparison of total response rate, correct response
      rate, and accuracy showed correct response rate to be the most consistently
      affected by changes in the ratio value. Substantial evidence of schedule control
      was seen only for correct responses. Incorrect response records were erratic, but
      rates generally declined as reinforcement was approached. Correct response
      records were characterized by increasing rate as reinforcement was approached. It
      was suggested that the pattern of fixed-ratio performance revealed may be
      affected by the behavioral unit examined.

PMID- 16811532
TI  - Responding in the pigeon under chained schedules of food presentation: the
      repetition of a stimulus during alternate components.
AB  - Key pecking in the pigeon was maintained under chained schedules in which the
      completion of one schedule component initiated the next component, and food was
      presented upon completion of a sequence of components. Under the chained
      schedules studied, a particular key color appeared during more than one
      component, and different key colors appeared during the other components. When
      seven 1-min fixed-interval components comprised a chained schedule and the
      response key was the same color during the first, third, fifth, and terminal
      components, patterns of positively accelerated responding were maintained during
      all but the first two components of each sequence. In general, response rates
      were always lowest during the first one or two components and highest during the
      terminal component when as few as three and as many as eight components comprised
      a schedule. Increasing the number of components from three to eight showed that
      response rate during a component increased when it was no longer one of the
      initial two components of the schedule, even though its temporal relation to food
      presentation had not changed. Finally, when seven components comprised a schedule
      and the response key was one color during the first, third, and fifth and a
      different color during the last component, response rates were low during the
      first five components and high during the last two components preceding food
      presentation.

PMID- 16811533
TI  - Two-key concurrent paced variable-interval paced variable-interval schedules of
      reinforcement.
AB  - Nine pigeons were used in two experiments in which a response was reinforced if a
      variable-interval schedule had assigned a reinforcement and if the response
      terminated an interresponse time within a certain interval, or class, of
      interresponse times. One such class was scheduled on one key, and a second class
      was scheduled on a second key. The procedure was, therefore, a two-key concurrent
      paced variable-interval paced variable-interval schedule. In Exp. I, the lengths
      of the two reinforced interresponse times were varied. The relative frequency of
      responding on a key approximately equalled the relative reciprocal of the length
      of the interresponse time reinforced on that key. In Exp. II, the relative
      frequency and relative magnitude of reinforcement were varied. The relative
      frequency of responding on the key for which the shorter interresponse time was
      reinforced was a monotonically increasing, negatively accelerated function of the
      relative frequency of reinforcement on that key. The relative frequency of
      responding depended on the relative magnitude of reinforcement in approximately
      the same way as it depended on the relative frequency of reinforcement. The
      relative frequency of responding on the key for which the shorter interresponse
      time was reinforced depended on the lengths of the two reinforced interresponse
      times and on the relative frequency and relative magnitude of reinforcement in
      the same way as the relative frequency of the shorter interresponse time depended
      on these variables in previous one-key concurrent schedules of reinforcement for
      two interresponse times.

PMID- 16811534
TI  - Concurrent performances: effect of punishment contingent on the switching
      response.
AB  - Pigeons' key-pecking responses were maintained under concurrently available
      variable-interval schedules of reinforcement. Responses in the presence of two
      different key-colors were reinforced on two independent and concurrent variable
      interval schedules of food reinforcement, each associated with one of the key
      colors (red or green). Pecks at a second key (changeover key), always white,
      would alternate the colors on the main key. In Exp. 1 and 2, electric shock of 50
      msec duration followed immediately after changeovers. The proportion of responses
      in the presence of the color associated with the higher frequency of
      reinforcements per hour was a direct function of shock intensity contingent on
      changeovers. When both schedules provided equal number of reinforcements per
      hour, there was no systematic effect of shock intensity on response distribution.
      In Exp. 3, a timeout period was contingent on changeovers, and response
      distribution was a function of timeout length.

PMID- 16811535
TI  - Concurrent schedules of reinforcement: effects of gradual and abrupt increases in
      changeover delay.
AB  - Pigeons' pecks were maintained on concurrent variable-interval 1-min variable
      interval 3-min schedules of reinforcement, with a changeover delay of 2 sec. When
      changeover delay was increased successively to 5.0, 7.5, and 12.5 sec (Exp. I)
      the actual relative rate of reinforcement for the variable-interval 3-min key
      decreased progressively for two birds, abruptly for two other birds, and the
      subjects devoted proportionately less of their time and responding to that key.
      However, the relative performance measures (relative time and relative
      responding) approximated the actual relative rate of reinforcement, with a
      maximum discrepancy of 11%, over all changeover delay values investigated.
      Experiment II attempted to lengthen response-run durations on the variable
      interval 3-min key so that they were long enough to meet the changeover delay
      requirement at each new changeover delay value, by progressively increasing the
      changeover delay by 0.5-sec increments. With this procedure the actual relative
      rate of reinforcement approximated more closely the scheduled relative rate as
      changeover delay increased. As in Exp. I, relative performance measures
      approximated the actual relative reinforcement rate (maximum discrepancy 17%).

PMID- 16811536
TI  - Changeover behavior under pairs of fixed-ratio and variable-ratio schedules of
      reinforcement.
AB  - Three pigeons were studied under a pair of equal fixed-ratio schedules and a pair
      of equal variable-ratio schedules. Each pair was arranged as independent,
      concurrent schedules and also in a non-independent relation where each peck in a
      schedule counted toward the response requirement of both schedules. The non
      independent pair of variable-ratio schedules maintained much higher changeover
      rates than any of the other three arrangements. Thus, two factors seemed
      necessary for generating high changeover rates. Responding on a schedule had to
      count toward the response requirement of both schedules, and the component
      schedules had to be variable. These data are consistent with the hypothesis that
      changeovers are at least partly controlled by the probability of reinforcement
      following a changeover.

PMID- 16811537
TI  - Control of responding by stimulus duration.
AB  - Pigeons were trained on a procedure in which the key was white for 30 sec,
      alternating with periods of darkness, or timeout. In a nondifferential training
      procedure, timeout duration was held constant at either 9 or 21 sec for different
      animals, and pecks on the white key were reinforced on a variable-interval 36-sec
      schedule. After 30 sessions an extinction generalization test was conducted where
      the duration of the timeout was varied from 3 to 27 sec. This test showed no
      differences in responding following timeouts of different durations. In a
      differential training procedure, timeout durations of either 9 or 21 sec were
      randomly scheduled for each animal. The variable-internal schedule was in effect
      following the same timeout duration as in the prior nondifferential procedure. No
      pecks were reinforced after the other timeout duration. In 40 sessions,
      differences in response rates following the two durations gradually developed. A
      maintained generalization procedure was then imposed in which timeout durations
      were varied from 3 to 27 sec, with the variable-interval schedule in effect
      following only the same duration as in the previous procedures. The first
      maintained generalization session showed that the prior differential training had
      established control of the animals' behavior by the timeout duration. In
      continued training on the maintained generalization procedure, control by the
      timeout duration decreased.

PMID- 16811538
TI  - Discrete-trials spaced responding in the pigeon: the dependence of efficient
      performance on the availability of a stimulus for collateral pecking.
AB  - Four pigeons were exposed to a discrete-trial schedule in which only responses
      spaced by at least 6 sec were reinforced. After 45, fifty-trial sessions, they
      failed to meet the spacing requirement in over 90% of the trials. When an
      alternative, non-contingent key (pecks on which had no consequence) was
      illuminated concurrently with the first key, the spacing performance of the three
      pigeons that pecked the non-contingent key improved so that they were obtaining
      75% of the possible reinforcers. These data demonstrated the importance of
      collateral behavior in mediating spaced performance. It was suggested that
      pigeons may successfully refrain from responding on the spacing procedure only
      when another stimulus correlated with reinforcement is available for pecking, and
      that the form that collateral behavior takes may, in general, be non-arbitrary,
      and species dependent.

PMID- 16811539
TI  - The role of information in the emission of observing responses: a test of two
      hypotheses.
AB  - Pigeons were trained on a trial procedure in a Skinner box. Each trial began with
      a fixed-interval schedule. Responding on this schedule produced a stimulus and a
      delayed trial outcome. The stimulus signalled whether the forthcoming outcome was
      reinforcement or nonreinforcement. Thus, the response was an observing response.
      When reinforcement was the outcome on 20% of the trials, response rates in the
      fixed interval were higher than when reinforcement was the outcome on 80% of the
      trials. This result is consistent with the hypothesis that observing responses
      are reinforced by the information associated with the stimulus signalling
      reinforcement. The result seems inconsistent with the hypothesis that observing
      responses are also reinforced by the information associated with the stimulus
      signalling nonreinforcement.

PMID- 16811540
TI  - Observing behavior in squirrel monkeys under a multiple schedule of reinforcement
      availability.
AB  - Observing behavior of two squirrel monkeys was examined under a multiple schedule
      of four components. Lever (observing) responses produced either a stimulus
      indicating the availability of food or another stimulus indicating food was not
      available. Key responses in the presence of the food-available stimulus produced
      food on a continuous reinforcement schedule. In the absence of food-available
      stimuli, responding on the key had no scheduled consequences. Observing responses
      produced food-available stimuli according to three different random-interval
      schedules with mean interstimulus availability times of 1, 2, and 4 min. In the
      fourth component of the multiple schedule (observing extinction) food-available
      stimuli never occurred. Each component of the schedule was correlated with a
      distinctive auditory stimulus. Observing rates decreased with decreasing
      frequency of the food-available stimulus. Observing rates during extinction
      continued decreasing when the brief stimulus indicating food unavailability was
      no longer produced by lever pressing. When the brief stimulus was reinstated
      response rates increased abruptly.

PMID- 16811541
TI  - A procedure for constant monitor of printout counter reset function.

PMID- 16811542
TI  - Some temporal parameters of non-contingent reinforcement.
AB  - In each baseline session, pigeons were exposed to a multiple schedule in which
      each of five distinctive stimuli was correlated with a different frequency of
      reinforcement. In one component, responses were reinforced with a probability of
      0.10 (random-ratio schedule); in the other four components, responses were
      reinforced with different scheduled temporal frequencies averaging 30 to 240 sec
      between reinforcements (random-interval schedules). For periods lasting 30
      sessions, contingent reinforcement was discontinued and reinforcement was
      presented independent of responding at irregular intervals averaging 30, 60, or
      120 sec, while the sequence of stimuli continued. After each such period, the
      baseline was reinstated for 30 sessions. The data indicated that: (1) The rate of
      responding in the presence of all stimuli decreased as exposure to the non
      contingent reinforcement procedure was prolonged, at all the frequencies of
      reinforcement employed; (2) The rate under the random-ratio schedule declined
      faster than the rates under all the random-interval schedules, presumably because
      the decrease in reinforcement frequency under this stimulus condition was
      greatest; (3) The decline in rates of responding under the stimuli correlated
      with the random-interval schedules tended to be greatest for the stimuli paired
      with the lowest frequencies of reinforcement.

PMID- 16811543
TI  - Some effects of response independent reinforcers in multiple schedules.
AB  - In Exp. I, rats' lever presses were conditioned on multiple variable-interval
      variable-interval schedules. Changing one of the multiple schedule components to
      variable time reduced responding in that component. Further reductions in
      responding occurred in both components when the schedule was changed to multiple
      variable-time variable-time. After reinstating the multiple variable-interval
      variable-time schedule, lower response rates were maintained in the variable-time
      component during a series of stimulus reversals. In Exp. II, replacement of
      extinction components of multiple variable-interval extinction or multiple
      extinction extinction with variable-time schedules for single sessions (probe)
      resulted in response rate increments in those components. In the former schedule
      these increases were concomitant with response decreases during the variable
      interval components. Response increases in the variable-time probes were related
      to conditioning history and, as a result, to response probability at the time of
      the probe.

PMID- 16811544
TI  - Delayed reinforcement in a multiple schedule.
AB  - Three rats and a pigeon were first trained on a two-component multiple schedule
      in which reinforcement in the two components occurred immediately after a
      response. Later, reinforcement in one component was delayed by a few seconds.
      During both stages of the experiment, reinforcement was scheduled by equal
      variable- (pigeon) or random-interval (rats) schedules in the two components. The
      main effect of the delayed reinforcement was to increase the rate of responding
      in the unchanged (non-delay) component. This behavioral contrast effect did not
      appear in all cases to be dependent upon a reduction in the rate of responding or
      the frequency of reinforcement in the delay component. This finding suggests that
      a reduction in response rate and/or reinforcement frequency in one component of a
      multiple schedule may not be a necessary prerequisite for the occurrence of
      behavioral contrast. This finding is, however, consistent with an explanation
      that suggests that behavioral contrast results from the introduction of a less
      preferred condition in one component of a multiple schedule, since it is known
      that animals "prefer" immediate to delayed reinforcement.

PMID- 16811545
TI  - Rates and patterns of responding with concurrent fixed-interval and variable
      interval reinforcement.
AB  - Pigeons were exposed to concurrent fixed-interval and variable-interval schedules
      of food reinforcement on two keys. The times between reinforcement were varied
      systematically on both keys. The overall relative frequency of responding on the
      fixed-interval key depended on the relative frequency of reinforcement, but did
      not match it. Instead, the ratio of responses on the fixed-interval key to
      responses on the variable-interval key was a power function of the ratio of
      reinforcements, with an exponent of 0.5. Patterns of responding between
      reinforcements on the fixed-interval key depended on both relative and absolute
      values of the reinforcement schedules. Similar overall relative responding was
      obtained at different absolute schedule values with equal relative reinforcement,
      despite some differences in patterns of responding.

PMID- 16811546
TI  - Effects of symmetrical and asymmetrical changeover delays on concurrent
      performances.
AB  - Two variable-interval 3-min schedules functioned concurrently to arrange
      reinforcement of a pigeon's pecks on a single key, the main key. Each schedule
      was associated with a distinct color of the main key; a response on a second key
      alternated the color and schedule assignment of the main key. A changeover delay,
      a period of time following schedule and key-color alternation during which
      reinforcement of responding on the main key could not occur, was arranged with
      equal or with unequal durations for the two directions of alternation. Durations
      were varied from 0.33 sec to 27 sec, in addition to no delay. With equal delays
      for the two directions of alternation, the pigeon alternated the schedules less
      often the larger the delay duration. When the delays in the two directions of
      alternation were unequal, it could be shown that alternation of the schedules was
      reduced both by a delay just incurred by the last alternation and by a. delay to
      be incurred by the next. The latter delay was more potent in reducing the
      frequency of alternations.

PMID- 16811547
TI  - Effects of cycle length on performance on a temporally defined avoidance
      schedule.
AB  - Three rats were trained on a temporally defined avoidance schedule logically
      similar to a fixed-interval, limited-hold positive reinforcement schedule. This
      avoidance schedule was composed of time periods during which responses had no
      scheduled consequences alternating with time periods during which a response
      precluded shock. As with fixed-interval length and response rate on positive
      reinforcement schedules, an inverse relationship was obtained between the length
      of the no-consequence interval and response rate during the no-consequence
      interval. An inverse relationship was also obtained between the length of the no
      consequence interval and the per cent of shocks avoided. A rate increase within
      the no-consequence interval, similar to that typically produced by fixed-interval
      positive reinforcement procedures, was displayed by one of the rats where the no
      consequence interval was at intermediate values and frequency of shock was
      relatively high. The introduction of a discriminative stimulus correlated with
      the avoidance interval produced typical discriminated avoidance behavior as well
      as alterations in temporal patterning of responses during the no-consequence
      interval in the two rats exposed to this procedure. These alterations in temporal
      patterning disappeared when the discriminative stimulus was removed. The results
      were consonant with those reported in the literature involving food reinforcement
      and fixed-interval, limited-hold schedules.

PMID- 16811548
TI  - Conditioned suppression of an avoidance response.
AB  - A signal followed by shock was presented at irregular intervals during a free
      operant avoidance schedule. The effects of this procedure were studied in terms
      of the rate of unavoided shock in the presence and absence of the signal and the
      rate of response before and during the signal. Three shock intensities were
      employed. Response enhancement as well as response suppression were observed;
      irrespective of changes in responding, shock rates substantially increased during
      signalled periods compared to non-signalled periods. Shock rates in non-signalled
      periods were generally higher than during training.

PMID- 16811549
TI  - Second-order schedules and the problem of conditioned reinforcement.
AB  - Thirteen pigeons were exposed to a variety of second-order schedules in which
      responding under a component schedule was reinforced according to a schedule of
      reinforcement. Under different conditions, completion of each component resulted
      in either (1) the brief presentation of a stimulus also present during
      reinforcement (pairing operation), (2) the brief presentation of a stimulus not
      present during reinforcement (nonpairing operation), or (3) no brief stimulus
      presentation (tandem). Brief-stimulus presentations engendered a pattern of
      responding within components similar to that engendered by food. Patterning was
      observed when fixed-interval and fixed-ratio components were maintained under
      fixed- and variable-ratio and fixed- and variable-interval schedules. There were
      no apparent differences in performance under pairing and nonpairing conditions in
      any study. The properties of the stimuli presented in brief-stimulus operations
      produced different effects on response patterning. In one study, similar effects
      on performance were found whether brief-stimulus presentations were response
      produced or delivered independently of responding. Response patterning did not
      occur when the component schedule under which a nonpaired stimulus was produced
      occurred independently of the food schedule. The results suggest a reevaluation
      of the role of conditioned reinforcement in second-order schedule performance.
      The similarity of behavior under pairing and nonpairing operations is consistent
      with two hypotheses: (1) the major effect is due to the discriminative properties
      of the brief stimulus; (2) the scheduling operation under which the paired or
      nonpaired stimulus is presented can establish it as a reinforcer.

PMID- 16811550
TI  - Shock-induced threat and biting by the turtle.
AB  - Shock-induced biting and threat by the male painted turtle (Chrysemys picta
      marginata) were studied in three experiments. When restrained facing each other,
      the turtles threatened and bit other turtles in response to electric shock. Shock
      alone caused turtles to threaten an unshocked turtle; the movements of a shocked
      turtle were sufficient to cause an unshocked but restrained turtle to threaten.
      When the turtles were free to move, they avoided an encounter when shocked, even
      reversing a strong position preference in order to do so.

PMID- 16811551
TI  - Avoidance of risk as a determinant of cooperation.
AB  - Pairs of subjects could either cooperate or respond on a lower paying individual
      task. Whenever both subjects chose to cooperate, either subject could make a
      response that took $1.00 of the other's earnings. In Exp. I, a stimulus signalled
      when a "take" response had been made. Either subject could avoid the loss by
      switching to the individual task within 5 sec after the stimulus appeared. Rates
      of cooperation were high when losses could be avoided but decreased again when
      the avoidance condition was removed. In Exp. II, a response prevented "takes"
      from occurring for a specified time interval after the response. This procedure
      also maintained cooperation. When each avoidance response subtracted from
      earnings, both avoidance responding and cooperation were eliminated.

PMID- 16811553
TI  - A cumulative recorder for experiments on concurrent schedules.

PMID- 16811552
TI  - Preference for qualitatively different reinforcers.
AB  - Three pigeons were studied under two-key concurrent variable-interval schedules
      with food as the reinforcer on one key and ectostriatal brain stimulation as the
      reinforcer on the other. Brain-stimulation parameters were kept constant while
      the rate of food reinforcement availability was varied. The results showed that
      qualitatively different reinforcers could be handled in the same theoretical
      framework that applies when choice is between different rates, immediacies, and
      amounts of a single reinforcer.

PMID- 16811554
TI  - The reinforcement of four interresponse times in a two-alternative situation.
AB  - Pigeons pecked for food in a two-key procedure. A concurrent variable-interval
      variable-interval schedule of reinforcement for two classes of interresponse
      times was arranged on each key. A visual stimulus set the occasion for potential
      reinforcement of the four operant classes: shorter and longer interresponse times
      on left and right keys. In Exp. I, the relative frequency of respones on a key
      equalled the relative frequency of reinforcement on that key. In Exp. II, the
      relative frequency of an interresponse time equalled the relative reciprocal of
      its length. In Exp. III, the relative frequency of an interresponse time was a
      monotonically increasing function of its relative frequency of reinforcement.
      These functions relating the relative frequency of an interresponse time to its
      relative length and to its relative frequency of reinforcement were the same as
      if there had been no second key. Also, the distribution of responses between keys
      was independent of the relative frequency of an interresponse time on either key.
      Experiment IV replicated Exp. I except that choices between keys were controlled
      by a stimulus that signalled the availability of reinforcement on the right key.
      A comparison of Exp. I and IV suggested that the relative frequency of an
      interresponse time on one key generally was independent of behavior on the other
      key, but that the number of responses per minute on a key did depend on behavior
      on the other key.

PMID- 16811555
TI  - Eliminating behavior with reinforcement.
AB  - Responding produced food according to a fixed-ratio schedule while the prevailing
      key-color alternated between red and blue. Stimulus durations were varied until a
      period was found that maintained equal rates of responding in the presence of
      both colors. Then, food presentation was discontinued in the presence of one
      stimulus and made dependent on not responding in the presence of the other. Food
      presentation dependent on not responding reduced the rate of responding faster
      than did extinction. Spontaneous recovery occurred only during the stimulus
      correlated with extinction.

PMID- 16811557
TI  - A device for measuring food-magazine behavior in the pigeon.

PMID- 16811556
TI  - An improved method of housing pigeons.

PMID- 16811558
TI  - Temporal tracking on cyclic-interval reinforcement schedules.
AB  - Pigeons were exposed to four cycles per session of a schedule in which the
      duration of successive interreinforcement intervals differed by t-sec. A cycle
      was composed of seven increasing and seven decreasing intervals, from 2t to 8t
      sec in length. In Exp. 1, postreinforcement pause tracked interval duration on
      five cyclic schedules, with values of t ranging from 2 to 40 sec. Tracking was
      better at shorter t values, and when discriminative stimuli signalled increasing
      and decreasing parts of the cycle. Pooled data for the whole experiment showed
      postreinforcement pause to bear a power function relationship to interval length,
      with a smaller exponent than the comparable function for fixed-interval
      schedules. Tests in a second experiment showed that pigeons trained on an
      arithmetic progression could also track schedules in which successive intervals
      followed either a logarithmic or a geometric progression, although tracking was
      more stable in the logarithmic case.

PMID- 16811559
TI  - Behavioral contrast as a function of the duration of an immediately preceding
      period of extinction.
AB  - For four pigeons key-peck responding was reinforced on a variable-interval
      reinforcement schedule in the presence of a vertical white line. When response
      rates had stabilized a horizontal white line was introduced, in the presence of
      which reinforcement was not available (extinction). The horizontal line was
      presented once per session, immediately before the vertical line was presented.
      The duration of the horizontal line varied randomly from session to session,
      being either 0 sec (i.e., no presentation), 10 sec, 30 sec, 2 min, 10 min, 40
      min, or 120 min. When the horizontal line was present for more than 0 sec,
      behavioral contrast was obtained in the presence of the following vertical line.
      Contrast increased with increasing durations of the horizontal line, asymptoting
      when the horizontal line was present for 40 min.

PMID- 16811560
TI  - Behavioral contrast and response independent reinforcement.
AB  - Four pigeons received pre-training that included presentation of the reinforcer
      independently of behavior and then baseline training on a variable-interval
      schedule of reinforcement. With the introduction of a multiple schedule, in which
      the first stimulus was associated with a response contingent and a second
      stimulus with a response independent, 1-min variable-interval schedule, a
      reduction in response rate was obtained in the second component, which was not
      accompanied by a behavioral contrast effect in the first component. A further
      three pigeons were given the same pre-training and baseline training before the
      introduction of an otherwise identical multiple schedule, in which no
      reinforcement occured in the second component. Behavioral contrast was obtained
      from all three subjects. The results indicated that under conditions of constant
      reinforcement density a reduction in responding is not a sufficient condition for
      the occurrence of behavioral contrast.

PMID- 16811561
TI  - Commitment, choice and self-control.
AB  - When offered a choice (Choice Y) between a small immediate reward (2-sec exposure
      to grain) and a large reward (4-sec exposure to grain) delayed by 4 sec, pigeons
      invariably preferred the small, immediate reward. However, when offered a choice
      (Choice X) between a delay of T seconds followed by Choice Y and a delay of T
      seconds followed by restriction to the large delayed reward only, the pigeon's
      choice depended on T. When T was small, the pigeons chose the alternative leading
      to Choice Y (and then chose the small, immediate reward). When T was large, the
      pigeons chose the alternative leading to the large delayed reward only. The
      reversal of preference as T increases is predicted by several recent models for
      choice between various amounts and delays of reward. The preference for the large
      delayed alternative with long durations of T parallels everyday instances of
      advance commitment to a given course of action. Such commitment may be seen as a
      prototype for self-control.

PMID- 16811562
TI  - Applications of matrix switching.

PMID- 16811563
TI  - Concurrent performances: rate and accuracy of free-operant oddity responding.
AB  - In pigeon's oddity performances, maintained by variable-interval reinforcement of
      pecks on the odd key of three keys in a triangular array, accuracy and response
      rate varied inversely with the rate of variable-interval reinforcement scheduled
      concurrently for pecks on a fourth, spatially isolated key. But when variable
      interval and extinction components alternated in a multiple schedule for pecks on
      the spatially isolated key, oddity accuracy was greater during variable-interval
      components than during extinction components. Oddity response rate was not
      affected systematically by the alternating components. Changeovers between the
      oddity keys and the spatially isolated key were frequent during variable-interval
      components; responding occurred almost exclusively on the oddity keys during
      extinction components. This difference in performance during the two components
      was eliminated by arranging stimulus-correlated variable-interval reinforcement
      in the multiple schedule on the spatially isolated key: a stimulus was presented
      in the variable-interval components only when reinforcement became available,
      thereby reducing responding on this key to near-zero levels in both components
      while maintaining the variable-interval reinforcement. The effect of the multiple
      schedule components on oddity accuracy was not altered, however, and thus
      apparently depended directly on concurrent reinforcement and not on differential
      sequential properties of concurrent responding during the two components.

PMID- 16811564
TI  - Some effects of interreinforcement time upon choice.
AB  - Pigeons' responses were reinforced on two identical and concurrently available
      chain variable-interval-schedules. Unlike the typical concurrent chains
      procedure, both links were operative throughout, thus producing three types of
      concurrency: (1) concurrent initial links; (2) concurrent initial and terminal
      links; (3) concurrent terminal links. Choice proportions in each of these three
      states suggested that the pigeons were sensitive to momentary likelihoods of
      reinforcement: choice proportions for a schedule were higher when the schedule
      had been operative for some time, resulting in a higher probability of
      reinforcement. The study also showed that the relative rates of responding did
      not match the relative rates of reinforcement in any of the three states of
      concurrency. Instead, the choice proportions in both the concurrent initial and
      in the concurrent terminal links were intermediate between the scheduled and the
      obtained relative rates of reinforcement, while the choice proportions for a
      terminal link concurrent with an initial link consistently overmatched the
      relative interreinforcement times (and were typically 1.00). These data indicate
      that an accurate characterization of choice may not be obtained by considering
      only the relative interreinforcement interval where one interreinforcement
      interval is segmented into a chain. Instead, the organism's choice for a schedule
      will be substantially lowered by the chaining operation.

PMID- 16811565
TI  - Inverse relation between choice and local response rate with a schedule of
      response-produced blackouts.
AB  - Pigeons were exposed to a two-key concurrent chains schedule in which identical
      frequencies and distributions of food presentations generated different response
      rates in the terminal links. An inverse relation between local rate of response
      in the terminal links and relative frequency of response in the initial links was
      observed. The high response rate was produced in one terminal link by a second
      order schedule in which responding produced brief blackouts of the response key.
      Responding under the same schedule in the other terminal link did not produce
      blackouts. Under initial training and after spatial reversal of the terminal-link
      schedules, two of three pigeons had lower relative frequencies of response in the
      initial member of the chain with the higher terminal link response rate. The
      third pigeon showed no change in preference at reversal.

PMID- 16811566
TI  - Component duration and relative response rates in multiple schedules.
AB  - Pigeons were trained on a multiple variable-interval 30-sec, variable-interval 90
      sec schedule with each component presented alternately for an equal (on the
      average) duration. This average duration of exposure to each component was varied
      from 5 to 300 sec. The main concern was with rate of response in the variable
      interval 30-sec component relative to rate of response in the variable-interval
      90-sec component. In all cases, rate of response was higher in the variable
      interval 30 sec component, but the discrepancy in the rate produced by the two
      schedules tended to be greatest when the duration of component presentation was
      brief. The mean proportion of responses emitted during the variable-interval 30
      sec component (responses in variable-interval 30-sec component divided by total
      responses) varied from about 0.60 to 0.71, where 0.75 would be expected on the
      basis of a matching rule, and 0.59 was that obtained by Lander and Irwin (1968).
      These results are in agreement with data reported by Shimp and Wheatley (1971)
      from a similar experiment.

PMID- 16811567
TI  - Positive interaction (induction) in multiple variable-interval, differential
      reinforcement-of-high-rate schedules.
AB  - The effect of increases in the rate of responding in one component of a multiple
      schedule upon the rate of responding in a second component was investigated.
      Pigeons were exposed to a multiple schedule where both components were initially
      variable-interval schedules having the same parameter value. After rate of key
      pecking stabilized, one component was changed to a schedule that differentially
      reinforced high rates of responding. Rate of reinforcement in this varied
      component was adjusted to remain equal to rate of reinforcement in the constant
      (variable-interval) component. Four of five pigeons showed a maintained increase
      in rate of responding during both the constant and varied components, even though
      rates of reinforcement did not change.

PMID- 16811568
TI  - Variable-time reinforcement in multiple and concurrent schedules.
AB  - Experiment I examined the role of a reduced rate of responding in the occurrence
      of behavioral contrast. Four rats and a pigeon were exposed to a two-component
      multiple schedule in which one component was always a variable-interval schedule.
      The second component was, at different times, either a variable-time schedule in
      which food was delivered independently of responding, or extinction. Both
      extinction and the variable-time schedule reduced the rate of responding in the
      second component. Behavioral contrast was observed, however, only when extinction
      was scheduled in the second component. Experiment II examined preference, as
      measured by time allocation in concurrent schedules for a variable-interval
      schedule relative to a variable-time schedule. Two rats displayed a lack of
      preference between the two schedules. The results of these experiments support a
      preference interpretation of behavioral contrast, which holds that behavioral
      contrast is the result of the introduction of a less-preferred condition in one
      component of a multiple schedule.

PMID- 16811569
TI  - Intermittent reinforcement of an interresponse time.
AB  - Rats were exposed to schedules in which reinforcement was contingent upon the
      emission of a 1.0- to 2.0-sec interresponse time. The rate of emission and the
      temporal distribution of this interresponse time was recorded. Several different
      contingencies between the emission of the interresponse time and reinforcement
      were examined. Both the rate of emission and the temporal distribution of the 1.0
      to 2.0-sec interresponse time varied as a function of the schedule on which it
      was reinforced. This finding, which suggests that an interresponse time behaves
      as other operants, has implications for the analysis of conventional
      reinforcement schedules in terms of the differential reinforcement of
      interresponse times.

PMID- 16811570
TI  - Fixed-interval limited-hold avoidance with and without signalled reinforcement.
AB  - Rats trained to lever press on a fixed-interval limited-hold avoidance schedule
      maintained a pattern of responding similar to that maintained by fixed-interval
      limited-hold schedules of positive reinforcement. But this positively accelerated
      pattern of behavior was maintained only when the occurrence of reinforcement was
      signalled by the presentation of a brief flash of light. This result suggests
      that the discriminative function of the reinforcer in avoidance is less
      pronounced than the discriminative function of the reinforcer in escape or
      positive reinforcement. It also suggests that the distinction between positive
      reinforcement and avoidance is not superfluous. Although the schedule of
      reinforcement is an important variable in determining the pattern of behavior,
      other variables, such as the nature (i.e., stimulus presentation, termination, or
      omission) of the reinforcer, are also potent determinants of behavior.

PMID- 16811571
TI  - A monkey-resistant lever switch for avoidance conditioning.

PMID- 16811572
TI  - Post-reinforcement pauses and response rate of monkeys on a two-hand fixed-ratio
      schedule.
AB  - Fixed-ratio behavior of monkeys was analyzed separately for two hands. While one
      hand responded on the fixed-ratio schedule the other performed a holding response
      and the function of the hands changed in alternate ratio runs. After performance
      was stable on the fixed ratio (70 responses, two monkeys; 100 responses, two
      monkeys, 120 responses, two monkeys) 90 sessions of further training equalized
      post-reinforcement pauses and the mean interresponse time of the two hands. Hand
      preference in reaching for food remained unchanged. Then, the fixed-ratio
      requirement was changed (a) in small sequential steps, (b) in two large steps,
      and, (c) within sessions alternating two runs at a high ratio with two runs at a
      low ratio. The mean duration of post-reinforcement pauses was correlated with a
      fixed ratio maintained throughout a session but single pauses were neither
      controlled by the immediately preceding nor by the following ratio run when a cue
      to its length was available. The mean interresponse time was insensitive to
      changes in fixed ratio. The fixed-ratio performance was generally similar to that
      of pigeons and rats.

PMID- 16811573
TI  - Fixed-ratio performance under conditions of delayed reinforcement.
AB  - Four rats were trained on a schedule in which completion of a fixed number of
      lever presses initiated a signalled delay period, at the end of which food was
      delivered. Lever presses made during the delay had no scheduled consequences.
      Delays of 12, 3, and 0.75 sec were used, and it was found that the latency of the
      first response after food (the post-reinforcement pause) increased with length of
      delay. There was, on the other hand, no consistent effect of delay upon rates of
      responding after the post-reinforcement pause.

PMID- 16811574
TI  - Airflow as a discriminative stimulus.
AB  - In one experiment, pigeons were taught to discriminate airflow by having
      availability of reinforcement signalled by its presence and extinction signalled
      by its absence. After they reached criterion, some were trained on a
      discrimination reversal. Others were trained on an intradimensional
      discrimination with a low airflow velocity associated with reinforcement and a
      higher airflow velocity associated with extinction. All discriminations were
      learned rapidly, indicating that airflow velocity can function as a
      discriminative stimulus. In the second and third experiments, naive pigeons were
      trained to discriminate the presence of a compound stimulus (one of three tonal
      intensities paired with one of three airflow velocities) from its absence. These
      pigeons were subsequently given a component stimulus test during extinction on
      four stimulus values; the two training values, the tone alone, and the airflow
      alone. High or moderate velocity airflow controlled more responding than any of
      the three tone intensities. However, low velocity airflow controlled more
      responding only when a low intensity tone was employed.

PMID- 16811575
TI  - Concurrent performances: synthesizing rate constancies by manipulating
      contingencies for a single response.
AB  - An earlier experiment scheduled variable-interval reinforcement for pigeons'
      pecks on one key, and variable-interval reinforcement alternating with
      extinction, in a multiple schedule, for pecks on a second key. During the second
      key's extinction component, first-key pecking was relatively slow and continuous,
      rarely interrupted by second-key pecking; during the variable-interval component,
      first-key pecking was frequently interrupted by second-key pecking. When
      changeover delays operated, so that reinforced pecks on one key could not follow
      closely upon changeovers from the other key, rapid first-key pecking between
      interruptions compensated sufficiently for the time lost in second-key pecking
      that the overall rate of first-key pecking remained roughly constant across the
      alternating multiple-schedule components. The present experiments duplicated, on
      a single key, the temporal pattern of first-key pecking generated in the earlier
      experiments: components of continuous key availability were alternated with
      components of interrupted key availability. Approximately constant overall rates
      of responding were observed with a single-key equivalent of a changeover delay
      scheduled after interruptions and with manipulations of the on-off durations of
      the interruption cycle. Rate constancies in the original concurrent situation
      presumably depended on analogous contingencies that operated upon the concurrent
      responses, rather than on any constant "reserve" of responses.

PMID- 16811576
TI  - Response control with titration of punishment.
AB  - Pigeons and rats were exposed to multiple schedules with different schedules of
      electric shock superimposed on identical schedules of food reinforcement during
      each of two components. During one component, (adjusting-intensity) the intensity
      of electric shock depended on responding. Each response increased the intensity
      while intensity decreased between responses. During the other component (constant
      intensity) the intensity was fixed at the value at which it had been adjusted at
      the end of the immediately preceeding adjusting-intensity component. In one
      experiment, shock was continuous during both components. In another experiment,
      instead of continuous shock, a brief pulse was delivered immediately after each
      response. During the adjusting-intensity component of both experiments, pigeons
      and rats responded at a rate just sufficient to keep the shock constant (critical
      rate). During the constant-intensity component, responding depended on whether
      shock was delivered continuously or in pulses. When shock was continuous,
      response rate during the constant-intensity component was higher than the
      critical rate. When shock was pulsed, response rate during the constant-intensity
      component was equal to the critical rate.

PMID- 16811577
TI  - Operant responding in the Bottlenose dolphin (Tursiops truncatus).

PMID- 16811578
TI  - Some effects of response-dependent clock stimuli in a fixed-interval schedule.
AB  - Two experiments studied the effects of brief response-dependent clock stimuli in
      fixed-interval schedules of reinforcement. In the first experiment, two pigeons
      were exposed to a fixed-interval schedule. Two conditions were compared. In both
      conditions each peck on the key produced a brief stimulus. In one condition,
      pecks produced a different stimulus in successive sixths of the interval. This
      was the clock condition. In the other condition, the same stimulus was produced
      throughout the interval. Response rates were lower and the pause after
      reinforcement was longer in the clock condition. In the second experiment, a two
      key optional clock procedure was used. Responding on the clock key produced one
      of three stimuli correlated with the three successive minutes of a fixed-interval
      schedule. A response on the other key produced grain at the end of the 3 min.
      When the final stimulus was removed from the situation and pecking produced
      nothing during the third minute, responding to the clock key declined to a very
      low rate. When the first two stimuli were removed and the third one replaced,
      responding to the clock key was resumed.

PMID- 16811579
TI  - Preference for mixed-interval versus fixed-interval schedules: number of
      component intervals.
AB  - Six pigeons were trained under a concurrent chains procedure so that preference
      for fixed-interval versus mixed-interval schedules with varying numbers of
      component intervals could be examined. The smallest and largest intervals in the
      terminal links were the same value as those used by Davison (1969). Relative
      choice in all cases approximated the relative means of the squares of the
      harmonic intervals to reinforcement in the terminal links, and no effect of
      number of component intervals was demonstrated. Mixed-interval versus fixed
      interval choice could not be predicted from extant data on fixed-interval versus
      fixed-interval choice.

PMID- 16811580
TI  - Fixed-interval behavior: effects of percentage reinforcement.
AB  - The percentage of fixed intervals terminating with food presentation was varied
      parametrically. Intervals that did not end with food were terminated by a
      stimulus uncorrelated with food presentation (a timeout stimulus). In Experiment
      I, the pigeons' response rates were an inverted U-shaped function of the
      percentage of food presentations: decreasing the percentage from 100% to 90%,
      70%, or 50% produced an increase in response rates; lower percentages decreased
      the rates. The patterns of responding in the 100% condition differed from those
      of the other conditions. In Experiment II, the chamber was darkened after food
      presentations and timeouts. Response rate was directly related to the percentage
      of food presentations: decreasing the percentage decreased the response rate.
      Characteristic fixed-interval patterns of responding were maintained as long as
      there were occasional food presentations; pausing followed by positively
      accelerated responding occurred in percentage conditions ranging from 7% to 100%.
      The ability to maintain fixed-interval performance with percentage reinforcement
      suggested that the behavioral sequences occurring in each interval may operate as
      unitary responses.

PMID- 16811581
TI  - Changing the response unit from a single peck to a fixed number of pecks in fixed
      interval schedules.
AB  - Each of three pigeons was studied first under a standard fixed-interval schedule.
      With the fixed interval held constant, the schedule was changed to a second-order
      schedule in which the response unit was the behavior on a small fixed-ratio
      schedule (first a fixed-ratio 10 and then a fixed-ratio 20 schedule). That is,
      every completion of the fixed-ratio schedule produced a 0.7-sec darkening of the
      key and reset the response count to zero for the next ratio. The first fixed
      ratio completed after the fixed-interval schedule elapsed produced the 0.7-sec
      blackout followed immediately by food. These manipulations were carried out under
      two different fixed-interval durations for each bird ranging from 3 min to 12
      min. The standard fixed-interval schedules produced the typical pause after
      reinforcement followed by responding at a moderate rate until the next
      reinforcement. The second-order schedules also engendered a pause after
      reinforcement, but responding occurred in bursts separated by brief pauses after
      each blackout. For a particular fixed-interval duration, post-reinforcement
      pauses increased slightly as the number of pecks in the response unit increased
      despite large differences in the rate and pattern of key pecking. Post
      reinforcement pause increased with the fixed-interval duration under all response
      units. These data confirm that the allocation of time between pausing and
      responding is relatively independent of the rate and topography of responding
      after the pause.

PMID- 16811582
TI  - Second-order schedules: brief shock at the completion of each component.
AB  - Pigeons worked on second-order schedules in which completion of fixed-interval
      component schedules was reinforced with food according to a variable-interval
      schedule of reinforcement. The completion of each fixed-interval component
      resulted in the presentation of a brief electric shock. In one condition (shock
      paired), the completion of every fixed-interval component, including those that
      ended in food, resulted in the shock. In another condition (shock-nonpaired),
      completion resulted in shock except for those components that ended in food.
      Shock presentations resulted in a positively accelerated rate within fixed
      interval components. This patterning within components was similar whether the
      shock was intermittently paired with food or not. Response rates tended to
      decrease as shock intensity increased. The characteristic fixed-interval response
      pattern within components did not occur when shock presentations were omitted at
      the end of each component (tandem schedule). When shocks were scheduled but food
      was no longer presented (extinction) response rates declined to a near-zero
      level. The performance under shock conditions is similar to that in other studies
      in which visual and auditory stimuli are presented at the completion of component
      schedules.

PMID- 16811583
TI  - Timeout and concurrent fixed-ratio schedules with human subjects.
AB  - Human subjects given choices among 10 different pairs of concurrent fixed-ratio
      schedules preferred the smaller ratio. After a preference had been determined,
      timeout of increasing duration followed the completion of the preferred schedule.
      The larger the fixed-ratio difference, the longer the timeout necessary to
      produce the shift to the previously nonpreferred ratio. Responses by two of three
      subjects were unaffected by changes from response-dependent to response
      independent pay.

PMID- 16811584
TI  - Effects on concurrent performances of a stimulus correlated with reinforcer
      availability.
AB  - A multiple schedule was arranged in which each component consisted of two,
      concurrent variable-interval schedules of reinforcement. A changeover-key
      procedure was used, and the components of the multiple schedule were
      distinguished (initially) by the color of the changeover key. During one
      component of the multiple schedule, the availability of a reinforcer arranged by
      one of the variable-interval schedules was marked by an exteroceptive stimulus,
      provided that that variable-interval schedule was not at the time assigned to the
      main key. During the other component of the multiple schedule, no reinforcer
      correlated stimuli were ever presented. During the latter component of the
      multiple schedule, the distribution of responses and time for the concurrent
      variable-interval schedules suggested control by the distribution of
      reinforcements. During the former component, most main-key responses were emitted
      on the key in the presence of which reinforcer-correlated stimuli were presented.
      Changeover rate in the presence of that key color was depressed. The
      discriminative control over the changeover was easily established and was
      reversible.

PMID- 16811585
TI  - Schedule control of the vocal behavior of Cebus monkeys.
AB  - The vocal behavior of three Cebus monkeys was maintained by fixed-ratio schedules
      of response dependent reinforcement at values between fixed-ratio 1 and fixed
      ratio 15. In one monkey that was exposed to variable-interval, fixed-interval,
      and conjunctive fixed-ratio fixed-interval schedules of reinforcement, vocal
      responding occurred at a low rate, but schedule-appropriate patterns were
      maintained. The rates and patterns of responding engendered indicated that the
      vocal operant can be brought under schedule control in the monkey by the use of
      response-dependent reinforcement.

PMID- 16811586
TI  - Compounding discriminative stimuli controlling free-operant avoidance.
AB  - The performances of three rats were stabilized on a multiple schedule that
      maintained responding by a free-operant avoidance schedule during independent
      presentations of tone and light. The simultaneous absence of these stimuli
      signalled shock-free periods and controlled response cessation. Subsequently,
      test sessions were administered consisting of independent presentations of each
      stimulus and these stimuli compounded (tone-plus-light). During an extinction
      test, additive summation was observed to the compounded stimuli, i.e., more
      responses were emitted to the compound than to either tone or light. During a
      series of 28 maintenance-test sessions in which the shock schedule remained
      operative, the compounded stimuli produced a generally enhanced response rate and
      fewer pauses terminating with shock than either single stimulus condition. These
      results extend the generality of free-operant additive summation to responding
      maintained by aversive control. In addition, a comparison of the present study
      with previous experiments reporting additive summation of positively reinforced
      responding indicates that similar variables-rate and aversive differences between
      training stimulus conditions-should be considered in accounting for response
      distributions during stimulus compounding when responding is controlled by either
      positive or negative contingencies.

PMID- 16811587
TI  - Conditioned suppression of free-operant avoidance.
AB  - The responses of white rats were maintained on an unsignalled free-operant
      avoidance schedule. Superimposed on the avoidance schedule was a blinking white
      light followed immediately by response-independent electric shock. Duration of
      the light stimulus was either 1 or 3 min. Avoidable shock was 1.5 mA; response
      independent shock was 7.5 mA. Suppression of responding during the light stimulus
      (both durations) developed over sessions. Responding immediately following the
      response-independent light-shock sequence was neither suppressed nor accelerated.
      The similarity is noted between the present result and findings of "positive
      conditioned suppression".

PMID- 16811589
TI  - A convenient and simple method of chronologically ordering journal issues.

PMID- 16811588
TI  - Preference for locus of punishment in a response sequence.
AB  - Food-deprived pigeons pecked a key under a schedule in which grain was made
      available after the seventieth peck. In each sequence of 70 responses, either the
      first, middle, or final response was followed by electric shock. Before the first
      response of each sequence, each response on a second key changed the color of the
      food key and the schedule of shock that was correlated with the food key color.
      Each pigeon preferred a schedule of shock, in that each of the three shock
      schedules did not occur equally often. The preferred shock schedule and the
      strength of the preference varied among the pigeons. The overall rate of
      responding by a pigeon under a given shock schedule was directly related to the
      pigeon's relative preference for that schedule, except when shock after the first
      response in the sequence was the most preferred schedule.

PMID- 16811590
TI  - The role of the response-reinforcer contingency in negative automaintenance.
AB  - When a response key is briefly illuminated before a grain reinforcer is
      presented, key pecking is reliably developed and maintained in pigeons, even if
      pecking prevents reinforcement (negative automaintenance). This experiment
      demonstrated that pigeons are sensitive to a negative response-reinforcer
      contingency, even though it does not eliminate responding. Within individual
      pigeons, two kinds of trials were compared: red key trials, in which
      reinforcement was negatively contingent on responding, and white key trials, in
      which reinforcement was unrelated to responding. Reinforcement frequency in non
      contingent trials was yoked to the obtained reinforcement frequency in negatively
      contingent trials. All eight pigeons pecked substantially more on the non
      contingent key than on the negative key, and preferred the non-contingent key to
      the negative key on occasional "choice" trials where both were presented
      together. When the stimuli correlated with the two conditions were reversed, the
      pigeons' behavior also shifted. These response differences are taken as evidence
      that pigeons are sensitive to the negative response-reinforcer contingency.

PMID- 16811591
TI  - Conditioning of a free operant in Octupus cyaneus Gray.
AB  - Operant conditioning was studied in six specimens of Octopus cyaneus Gray. An
      "arm-out-of-water" operant, in which the octopus inserted an arm up a feeding
      tube breaking the water surface, proved susceptible to reinforcement schedules.
      An apparatus was developed that provided automated reinforcement and recording.
      Performance was studied under continuous reinforcement, fixed-ratio and variable
      ratio schedules, and extinction conditions.

PMID- 16811592
TI  - Probability learning as a function of momentary reinforcement probability.
AB  - Pigeons were trained on a probability learning task where the overall
      reinforcement probability was 0.50 for each response alternative but where the
      momentary reinforcement probability differed and depended upon the outcome of the
      preceding trial. In all cases, the maximum reinforcement occurred with a "win
      stay, lose-shift" response pattern. When both position and color were relevant
      cues, the optimal response pattern was learned when the reinforcement probability
      for repeating the just-reinforced response was 0.80 but not when the probability
      was 0.65. When only color was relevant, learning occurred much more slowly, and
      only for subjects trained on large fixed ratio requirements.

PMID- 16811593
TI  - Performance in concurrent interval schedules.
AB  - Four pigeons were trained under concurrent variable-interval variable-interval
      and fixed-interval variable-interval schedules in a two-key situation. Both
      response allocation and time allocation to the two schedules were measured when
      various reinforcement rates were arranged on each key. All animals showed an
      approximately constant proportional preference for the variable-interval schedule
      over the fixed-interval schedule. These results support Schneider's (1969)
      analysis of fixed-interval schedule performance.

PMID- 16811594
TI  - Performance in multiple fixed-interval schedules.
AB  - The performances of five pigeons were studied under a variety of multiple fixed
      interval schedules in which both component duration and reinforcement rate were
      varied. The three series of experimental conditions were: (a) when the ratio of
      component durations equalled the reciprocal of the ratio of component
      reinforcement rates; (b) when the component durations were equal; and (c) when
      the ratio of component durations equalled the ratio of component reinforcement
      rates. Relative response rates were related to relative reinforcement rates in
      the same manner as in multiple variable-interval schedules, but no effect of
      component duration was found.

PMID- 16811595
TI  - Reinforcement delay: some effects on behavioral contrast.
AB  - Thirty five White Carneaux pigeons first received 20 sessions of non-delayed
      reinforcement according to a multiple variable-interval 1-min variable-interval 1
      min schedule. For the remaining 15 sessions, subjects were assigned to one of
      five groups, with seven subjects per group. Four of these groups involved
      reinforcement according to the same multiple schedule as before, but
      reinforcement during one of the components was delayed for either 2.5, 5, 10, or
      120 sec. The schedule for the fifth group was changed to multiple variable
      interval 1-min extinction schedule of reinforcement. While some subjects in all
      groups showed behavioral contrast, it occurred more consistently in the groups
      involving extinction or the longer delays of reinforcement. Groups involving the
      various durations of delayed reinforcement or even extinction during the altered
      component did not, however, show a statistically significant difference in the
      amount of behavioral contrast. It was suggested that neither a reduction in
      reinforcement frequency nor response rate during the altered component is
      necessary to the production of behavioral contrast.

PMID- 16811596
TI  - Schedule-induced escape from fixed-interval reinforcement.
AB  - Pigeons trained to peck one of two keys for food were exposed to an ascending and
      descending series of fixed-interval values. A response on the second key produced
      an escape period consisting of a visual stimulus change. During escape periods,
      the fixed-interval timer continued to operate and even if it timed out, a
      response on the food key would not operate the feeder unless preceded by an
      escape-key response that terminated the escape condition. As the fixed-interval
      schedule was increased logarithmically through six values from 30 to 960 sec, the
      percentage of session time spent in escape as well as the frequency, duration,
      and rate of escape increased to a maximum and then decreased. One subject did not
      develop escape behavior to any significant degree. For all pigeons, escapes
      usually occurred after, rather than before, reinforcement.

PMID- 16811597
TI  - Aversive aspects of a fixed-interval schedule of food reinforcement.
AB  - The key pecking of pigeons was reinforced according to a fixed-interval schedule
      of reinforcement. The pigeons were also given the opportunity to attack a
      restrained target pigeon. The attack rates during the sessions of fixed-interval
      reinforcement were higher than during the operant level sessions in four of the
      five pigeons. Most attack occurred during the post-reinforcement pause in key
      pecking. It was suggested that a fixed-interval schedule of positive
      reinforcement possesses aversive properties, the most aversive of which are
      located during the post-reinforcement pause.

PMID- 16811598
TI  - Schedule-induced licking during multiple schedules.
AB  - Schedule-induced polydipsia was studied in rats bar pressing under two-component
      multiple schedules of food reinforcement. The first component of the multiple
      schedule was a variable-interval 1-min schedule throughout the experiment. The
      schedule comprising the second component was varied over blocks of sessions in
      terms of rate and magnitude of reinforcement, and was either variable-interval 3
      min (one pellet), variable-interval 3-min (three pellets), variable-interval 1
      min (one pellet), or extinction. Water intake per session varied with the rate of
      reinforcement in the schedule comprising the second component and was highest
      when the schedule was variable-interval 1-min. Both bar-pressing behavior and
      licking behavior showed behavioral interactions between the two components of the
      multiple schedules. With magnitude of reinforcement held constant, a matching
      relationship was observed between lick rate and reinforcement rate; the relative
      frequency of licks in the constant component matched the relative frequency of
      reinforcement in that component. Bar pressing, however, showed only a moderate
      degree of relativity matching. During the schedule-induced licking, a burst of
      licking followed each delivery of a pellet (post-prandial drinking). The duration
      of these bursts of licking was observed to be a function of the inter
      reinforcement interval.

PMID- 16811599
TI  - Maintenance and suppression of responding under schedules of electric shock
      presentation.
AB  - In squirrel monkeys previously trained under a continuous avoidance schedule,
      characteristic patterns of responding were maintained under a 3-min variable
      interval schedule of shock presentation (response-produced shock). Responding in
      the presence of a periodically presented stimulus, the termination of which
      coincided with the delivery of a response-independent electric shock (Estes
      Skinner procedure), was not reliably affected. When shocks followed every
      response during certain signalled portions of the session, and were presented
      under the variable-interval schedule during the rest of the session (multiple 1
      response fixed-ratio, 3-min variable-interval schedule of shock presentation),
      responding was suppressed during the fixed-ratio component and maintained during
      the variable-interval component. Environmental consequences do not have immutable
      properties, and may either support or suppress behavior, depending on the
      schedule of presentation.

PMID- 16811600
TI  - Variable location of punishment in a response sequence.
AB  - Key pecking of pigeons under a fixed-ratio 100, grain reinforcer schedule was
      followed by electric shock occurring once in each sequence of 100 responses with
      the shocked response varying irregularly in successive sequences. Under this
      shock schedule, a localized suppression of responding in a response sequence was
      not correlated with the probability of shock at different points in the sequence.
      High shock levels increased the duration of post-reinforcement pauses and
      suppressed responding during the first half of the response sequence. This
      suppression often persisted after the shocked response when shock occurred early
      in the sequence. The shock schedule did not produce a consistent suppressing
      effect on responding during the last half of the response sequence.

PMID- 16811601
TI  - Some effects of punishment upon unpunished responding.
AB  - Animals permitted free access to a running wheel and drinking tube increased the
      amount of running when drinking was punished with electric shock. Additional
      experiments demonstrated that the simple presence or absence of a drinking tube
      (or running wheel) was a sufficient condition to observe a decrease or an
      increase in the alternative response. A quantitative analysis of these
      interactions observed between the incompatible running and drinking responses
      suggested that each response occupied a constant proportion of the time available
      for it. These results question an interpretation of the increase in unpunished
      alternative responding based upon its avoidance properties.

PMID- 16811602
TI  - The relative aversiveness of signalled vs unsignalled escapable and inescapable
      shock.
AB  - In the first study, subjects escaped shock by pressing on a lever under an
      unsignalled condition. By pressing a different lever they changed the condition
      to signalled escape for three minute periods. The second study used the
      changeover procedure to study inescapable-unavoidable shock. Seven rats were used
      in each study. All subjects in both studies changed over from unsignalled to
      signalled conditions. Once contact with the signal condition was made, subjects
      responded to remain in that condition. The three different extinction conditions
      showed that the correlated stimulus without the signal had greater control over
      responding than the signal without the correlated stimulus. An analysis based
      upon shock and shock-free periods was presented.

PMID- 16811603
TI  - Three-configuration matching-to-sample in the pigeon.
AB  - Pigeons were trained on a zero-delay matching-to-sample procedure during which
      only three of the four possible stimulus configurations were presented.
      Subsequently, all birds were exposed to all four configurations as a transfer
      test. A high degree of negative transfer from the three training configurations
      was obtained in Experiment 1. The results of Experiment 2 indicated that three
      configuration training produced differential position-preference effects. During
      the transfer test, responding after one sample stimulus was apparently based on
      position, while responding after the other sample was based on color.

PMID- 16811604
TI  - The matching law.
AB  - The matching law may be viewed either as an empirical generalization, and therby
      subject to disproof, or as part of a system of equations used to define the
      utility ("value") of a reinforcer. In the latter case it is tautologous, and not
      subject to disproof within the defining context. A failure to obtain matching
      will most often be a signal that the independent variables have not been properly
      scaled. If, however, the proper transformations have been made on the independent
      variables, and matching is not obtained, the experimental paradigm may be outside
      the purview of the matching law. At that point, reinterpretations or revisions of
      the law are called for. The theoretical matching law is but one of many possible
      ways to define utility, and it may eventually be rejected in favor of a more
      useful definition.

PMID- 16811605
TI  - Two temporal parameters of food postponement.
AB  - Rats were trained to press a lever under schedules of food postponement. In the
      absence of lever presses, food was delivered periodically (food-food interval).
      Responses initiated a second interval (response-food interval) that was reset by
      each additional response. Performance was first studied at different response
      food intervals with the food-food interval fixed at 30 or 60 sec, or 10 min.
      Response-food intervals were examined in ascending order and then recovery was
      studied at shorter intervals. Finally, the food-food interval was manipulated
      with response-food interval fixed at 30 sec. At food-food intervals of 30 and 60
      sec, responding first increased and then decreased as the response-food interval
      increased. At the 10-min food-food interval, responding decreased with increasing
      response-food interval. In general, very low rates of responding occurred when
      the response-food interval was 60 sec or more and when it equalled or exceeded
      the food-food interval. However, responding was maintained in one animal when the
      food-food interval was decreased from 120 to 15 sec with the response-food
      interval at 30 sec. Results, in terms of several dependent variables, are
      compared with data on shock avoidance. Effects of response-independent and
      response-produced food and shock are discussed.

PMID- 16811606
TI  - Sustained behavioral contrast in children.
AB  - Children were exposed to a multiple schedule involving equal variable-interval
      schedules in each of two components and a multiple schedule involving a variable
      interval schedule in one component and an extinction schedule in the other.
      Response rates were equal in both components when each involved a variable
      interval schedule. Response rates differed in the two components of the multiple
      variable-interval extinction schedule. Response rates were higher in the variable
      interval schedule when the accompanying schedule was extinction than when it was
      variable interval. The increase in response rate in the variable-interval
      component, simultaneous with the decrease in response rate in the extinction
      component, illustrated sustained behavioral contrast, and was the first evidence
      of this phenomenon in children.

PMID- 16811607
TI  - Effects of concurrent schedules on human fixed-interval performance.
AB  - Young adults performed a lever-pressing task for money on two schedules of
      reinforcement: concurrent fixed-interval 1 min-differential-reinforcement-of-low
      rate 20-sec, and concurrent fixed-interval 1-min-fixed ratio 100 responses. All
      subjects were trained on both schedules. Fixed-interval performance concurrent
      with the differential reinforcement procedure was characterized by high constant
      rates with no post-reinforcement pauses. Fixed-interval performance concurrent
      with fixed ratio was characterized by low rates and lengthy post-reinforcement
      pauses. These results differ from those obtained in prior studies on the effects
      of conditioning history upon subsequent fixed-interval performance. The prior
      work, using non-concurrent procedures, had shown that fixed-interval performance
      following differential reinforcement of low rates was characterized by post
      reinforcement pauses and low rates, while fixed-interval performance following
      fixed ratio exhibited high constant rates and no post-reinforcement pause. The
      present results suggest that alternative concurrent contingencies are another
      major determinant of human fixed-interval performance.

PMID- 16811608
TI  - Conditioned suppression with extinction as the signalled stimulus.
AB  - The key pecking of pigeons that was maintained by a 60-sec random-interval
      schedule of food reinforcement was suppressed during a variable-duration warning
      stimulus that signalled a 5-min extinction period. The onset of the extinction
      period immediately followed the termination of the warning signal and was
      independent of the subject's responses. All subjects eventually showed nearly
      complete suppression of responding during the warning stimulus.

PMID- 16811609
TI  - A yoked-chamber comparison of concurrent and multiple schedules.
AB  - Pigeons were exposed to alternative pairs of variable-interval schedules
      correlated with red and green lights on one key (the food key). In one
      experimental chamber, responses on a white key (the changeover key) changed the
      color of the food key and initiated a 2-sec changeover delay. Pigeons in a second
      chamber obtained food by pecking on a colored key whenever the pigeons in the
      first (concurrent) chamber had obtained food for a peck on that key color. There
      was no changeover key in the second (multiple) chamber: changeover responses in
      the first chamber alternated the schedules and colors in both chambers. The
      pigeons in both chambers emitted the same proportion of responses on each of the
      variable-interval schedules, and mastered discrimination reversals at the same
      rate. The pigeons differed only in their absolute response rates, which were
      greater under the concurrent schedules. In a second experiment, changes in key
      color occurred automatically, with different proportions of time allocated to the
      two variable-interval schedules. Matching of relative response frequency to
      relative reinforcement frequency was affected by the relative amounts of time in
      each component, by rate of changeovers, and by manipulations of the variable
      interval scheduling.

PMID- 16811610
TI  - Reponse-reinforcer independence and conventional extinction after fixed-interval
      and variable-interval schedules.
AB  - After training three albino rats to bar press during a multiple fixed-interval
      variable-interval schedule, the response-reinforcer dependency was simultaneously
      removed from both components, converting the schedule to multiple fixed-time
      variable-time. Response rates were reduced in both components under these
      conditions but the fixed-time schedule maintained relatively higher response
      rates with each rat. After reinstating the response-reinforcer dependency in both
      components, responding was conventionally extinguished by rendering the pellet
      dispenser inoperative. Responding rapidly decreased to near-zero levels.
      Differences in fixed and variable-time schedules in sustaining behavior are
      discussed in terms of differences in response rates at the time of reinforcer
      delivery. Similarities and differences between conventional extinction and
      schedules delivering response-independent reinforcers are also discussed.

PMID- 16811611
TI  - Effects of different delay of reinforcement procedures on variable-interval
      responding.
AB  - Two experiments studied responding in the rat when the first bar press after a
      variable period of time produced a cue light that remained on for either 10, 30,
      or 100 sec and terminated with the delivery of food. In Experiment I, response
      rate decreased and time to the first response after reinforcement increased as
      the delay of reinforcement increased. Similar results were obtained whether the
      delay consisted of retracting the lever during the delay, a fixed delay with no
      scheduled consequence for responding, or every response during the delay
      restarted the delay interval. In Experiment II, fixed-delay and fixed-interval
      schedules of the same duration during the delay period had no differential effect
      on either response rate or time to the first response after reinforcement, but
      differentially controlled responding during the delay periods.

PMID- 16811612
TI  - Incompatability between the pigeons' unconditioned response to shock and the
      conditioned key-peck response.
AB  - High-speed photography was used to compare the pigeon's response to unsignalled
      shock with the pigeon's key-peck response. During shock, pigeons flex their neck
      (i.e., the distance between their eyes and shoulders decreases). Following shock,
      the neck is extended. During key pecking, the neck remains extended and the head
      moves toward the key in a slight arc as though attached to a fixed fulcrum.
      Response topography during pecking and shock appear to be incompatible, and it is
      concluded that the difficulty in key-peck training pigeons to escape electric
      shock is due to interference from the unconditioned flexion response. This
      conclusion supports the species-specific defense theory of escape and avoidance
      behavior.

PMID- 16811613
TI  - Responding in the squirrel monkey under second-order schedules of shock delivery.
AB  - Lever-pressing responses were maintained in the squirrel monkey when the only
      consequence of responding was the delivery of a response-produced electric shock,
      or alternatively, a brief visual stimulus that was occasionally followed by an
      electric shock. When shock was produced by the first response occurring after 8
      min (8-min fixed-interval schedule), a period of no responding at the beginning
      of the interval was followed by a gradual increase in response rate during the
      interval. Similar rates and patterns of responding were maintained when a 1-sec
      visual stimulus was produced by the first response occurring after 8 min and
      shock delivery followed the brief stimulus. Subsequently, patterns of positively
      accelerated responding were engendered during individual fixed-interval
      components when the first response occurring after 4 min produced a 1-sec visual
      stimulus and shock delivery followed the second, and later the fourth,
      presentation of the 1-sec stimulus. When the duration of the brief stimulus was
      varied over a 100-fold range from 0.1 to 10.0 sec (1) mean response rates
      decreased monotonically as stimulus duration increased, and (2) patterns of
      positively accelerated responding were least variable and response rates during
      the initial part of each 4-min interval were lowest at a stimulus duration of 1
      sec.

PMID- 16811614
TI  - Unsignalled avoidance in a shuttlebox: a rapid acquisition, high-efficiency
      paradigm.
AB  - Detailed descriptive data are provided on the free-operant avoidance behavior of
      rats in a shuttlebox during both acquisition and terminal performance. Initially,
      eighteen 21-min acquisition sessions were given. Each hurdle-cross postponed the
      next shock 20 sec (response-shock interval) and shocks were scheduled every 5 sec
      (shock-shock interval) in the absence of a response. All eight subjects avoided
      over 70% of the shocks due (12/min) in Session 1. Maximum response rates were
      reached by the third session and declined slowly while shock rates continued to
      drop slowly through Session 15. Three subjects were run an additional five months
      with a response-shock interval of 20 sec and their terminal response rates were
      all under five responses per minute and shock rates were 0.07 per minute.
      Interresponse time distributions for terminal performance showed that over 95% of
      all responding by all three subjects occurred in the last half of the response
      shock interval.

PMID- 16811615
TI  - The psychological distance to reward.
AB  - Pigeons' responses in the presence of two concurrently available (initial-link)
      stimuli produced entry into one of two different and mutually exclusive terminal
      link stimuli according to identical but independent variable-interval schedules.
      In one experiment, a two-component chained fixed-interval schedule produced food
      in one terminal link while a simple fixed-interval schedule produced food in the
      other terminal link. When the interreinforcement intervals were equal in the two
      terminal links (i.e., the simple fixed-interval was twice the size of each of the
      components in the chained schedule) pigeons preferred the simple fixed-interval
      as measured by their relative rates of responding in the concurrently available
      initial links. This preference increased as the duration of the terminal links
      increased. The preference could be reversed by making the simple fixed-interval
      schedule sufficiently longer than the chained schedule. In the second experiment,
      the terminal links consisted of two- vs three-component chained fixed-intervals,
      again with equal interreinforcement intervals. Pigeons preferred the two
      component chain to the three-component chain, although these results were less
      consistent and less dramatic than those in the first experiment. Again,
      preference increased as the duration of the terminal links increased. The results
      show that an organism's choice for a schedule will be substantially lowered by
      the chaining operation even when the interreinforcement interval remains
      constant.

PMID- 16811616
TI  - Choice behavior and the accessibility of the reinforcer.
AB  - In Experiment 1, matching of relative response rates to relative rates of
      reinforcement was obtained in concurrent variable-interval schedules when the
      absolute values of the two concurrent variable-interval schedules varied from 6
      sec and 12 sec to 600 sec and 1200 sec. Increases in the duration of the
      changeover delay, however, produced decreases in the relative response rates and,
      consequently, some deviation from matching. In Experiment 2, matching of relative
      response rates to the relative duration of the reinforcer failed to occur when
      the equal variable-interval schedules arranging access to the two different
      reinforcer durations (1.5 and 6 sec) were varied in size from concurrent variable
      interval 10-sec schedules to concurrent variable-interval 600-sec schedules.

PMID- 16811618
TI  - Construct a monochromator from a single interference filter.

PMID- 16811617
TI  - Choice between two-component chained and tandem schedules.
AB  - Pigeons were trained on a two-key choice procedure in which a pair of equal and
      concurrently available variable-interval schedules (initial links) arranged entry
      into one or the other of two mutually exclusive schedules (terminal links) that
      ended in primary reinforcement. The terminal links were two-component chained or
      tandem schedules. Responses during the initial links were distributed equally on
      the two keys whenever the terminal links were associated with the same sets of
      interreinforcement intervals. Whether or not the terminal-link interreinforcement
      intervals were the same on the two keys, initial-link responding was affected by
      neither the presence nor relative durations of differentially signalled
      components within a terminal-link schedule. The simplest interpretation of these
      results is that initial-link responding is maintained directly by delayed primary
      reinforcement, rather than conditioned reinforcement afforded by the stimuli
      correlated with the terminal-link schedule components. This finding suggests that
      aspects of chained schedule performance usually attributed to conditioned
      reinforcement might best be reinterpreted in terms of delayed primary
      reinforcement and various discriminative functions served by the component
      correlated stimuli.

PMID- 16811619
TI  - Accuracy of performance on a matching-to-sample procedure under interval
      schedules.
AB  - Correct matches on a matching-to-sample procedure were reinforced under fixed
      interval, chained fixed-interval, and fixed-interval schedules with exteroceptive
      stimulus changes correlated with time since the last reinforcer (an added clock).
      For all four pigeons, accuracy changed within the fixed-interval and fixed
      interval schedules with added clock, decreasing from the beginning of the
      interval to some point in the middle. The performance then became increasingly
      more accurate until the end of the interval. Under the chained schedules,
      accuracy also changed within the components. During the initial component,
      accuracy decreased from the beginning of the fixed interval to some point in the
      middle or at the end. During the middle component, the performance usually
      remained at an intermediate level of accuracy. During the terminal component, the
      initially inaccurate performance became increasingly more accurate throughout the
      interval. Systematic relationships between response rate and per cent error
      showed that all four pigeons performed most accurately at high rates. The
      accuracy of the performance at low rates was also quite high. These relationships
      held for all three types of schedules through an eight-fold variation in
      scheduled interreinforcement time.

PMID- 16811620
TI  - A test of the negative discriminative stimulus as a reinforcer of observing.
AB  - Five pigeons were used to test the hypothesis that the source of reinforcement
      for observing behavior is the information that it provides concerning the
      schedule of primary reinforcement. On a variable-interval schedule, pecking the
      left-hand key produced a 30-sec display of such information. During this 30-sec
      period, when pecking the right-hand key was reinforced on a random-interval
      schedule, both keys were green; when no reinforcement was scheduled (extinction)
      both keys were red. Later, this baseline procedure, in which both red and green
      were available, was replaced for blocks of sessions by procedures in which either
      (a) the red was eliminated and only the green could be produced; or (b) the green
      was eliminated and only the red could be produced. The results were that green
      maintained rates of pecking on the left key that were as high or higher than when
      both colors were available and that red maintained no responding. It was
      concluded that the reinforcing value of a stimulus depends on the positive or
      negative direction of its correlation with primary reinforcement, rather than
      upon the amount of information that it conveys.

PMID- 16811621
TI  - Behavioral definition of minimal reaction time in monkeys.
AB  - Two monkeys (Macaca mulatta) were trained to press a key after onset of a tone
      and to release it after a 1-sec fixed foreperiod terminated by a light. The
      effects of imposing temporal contingencies on key release reaction times were
      determined by reinforcing only those releases whose latencies from the light fell
      within a "payoff band", two time limits 50 msec apart located at some delay
      following the light. Over several days this delay was first gradually decreased,
      shortening the interval between light and payoff band, and then gradually
      increased again. For each delay, the median reaction time and a measure of
      variability were obtained from the latency distribution. For both animals, median
      latency could be decreased to 180 msec with the variability remaining small.
      Moving the payoff band still closer to the light resulted in further decrease in
      median latency but an abrupt increase in variability. This is in agreement with a
      model for simple reaction time derived from human research which suggests that
      this increased variability results from the inclusion of high-variability
      foreperiod time estimations in the latency distribution. These results indicate
      that interpretation of monkey response latencies as "minimal reaction times"
      requires examination of temporal reinforcement contingencies and variability of
      latencies.

PMID- 16811622
TI  - Responding under discrete-trial fixed-interval schedules of reinforcement.
AB  - A fixed-interval schedule of reinforcement was modified by dividing each interval
      into 4-sec trial periods. No more than one response could occur during each trial
      because the operandum was inactivated for the remainder of any trial in which a
      response occurred. For example, under a 28-sec schedule, no more than seven
      responses could be emitted between reinforcements. Probabilities of responding by
      pigeons under six values of this discrete-trial fixed-interval schedule were best
      described by a two-state model: responding was either absent or infrequent
      immediately after reinforcement; then, at some variable time after reinforcement,
      there was an abrupt transition to a high and constant probability of responding
      on each trial. Performances under the discrete-trial procedure were less affected
      by uncontrolled sources of variance than performances under equivalent free
      operant fixed-interval schedules.

PMID- 16811623
TI  - Two different kinds of key peck in the pigeon: some properties of responses
      maintained by negative and positive response-reinforcer contingencies.
AB  - Pigeons emitted almost exclusively short-duration key pecks (shorter than 20
      msec) when on negative automaintenance procedures, in which pecks prevented
      reinforcement. Peck durations under fixed-interval and fixed-ratio reinforcement
      schedules were generally two to five times longer than pecks under a negative
      automaintenance schedule. However, initial key pecks were of short duration,
      independent of procedure. The frequency of short-duration pecks was insensitive
      to differential reinforcement, while the frequency of long-duration pecks was
      sensitive to differential reinforcement. It is proposed that short-duration pecks
      arise from the pigeon's normal feeding pattern and are directly enhanced by food
      presentation, while long-duration pecks are controlled by the contingent effects
      of food presentation. The implications of the existence of two classes of pecks
      for the functional definition of operants and the separation of phylogenetic and
      ontogenetic sources of control of key pecking are discussed.

PMID- 16811624
TI  - The development of stimulus control with and without a lighted key.
AB  - In two experiments, the effect of an illuminated response key on the acquisition
      of stimulus control by an airflow stimulus was assessed. In the first experiment,
      pigeons were given nondifferential training with airflow emerging from behind the
      response key in one of three conditions of illumination: trained to peck a
      lighted key, trained to peck an unlighted key with a houselight present, trained
      to peck a key in total darkness. After 10 days of training on a variable-interval
      schedule of reinforcement, all subjects were given a generalization test on
      airflow velocity. The gradients for subjects trained in the dark were sharp,
      while those for subjects trained in lighted conditions were shallow. In the
      second experiment, the effect of an irrelevant keylight on the acquisition of an
      airflow velocity discrimination was assessed. Two groups of pigeons were trained
      to discriminate two airflow velocities. One group was trained with a lighted
      response key and the other was trained to peck the response key in total
      darkness. The dark-trained subjects acquired the discrimination more rapidly. The
      results demonstrate that the acquisition of stimulus control by airflow with
      either a differential or nondifferential training procedure can be overshadowed
      by keylight.

PMID- 16811625
TI  - Reinforcement omission on temporal go-no-go schedules.
AB  - Either a partial blackout, or the blackout plus a "feeder flash", occurred in
      lieu of reinforcement on two procedures that produced opposite patterns of
      responding after reinforcement. Response rate was elevated after reinforcement
      omission on the procedure that produced a "pause-and-respond" pattern following
      reinforcement, but depressed after reinforcement omission on the procedure that
      produced a "respond-and-pause" pattern. The effect of blackout plus feeder flash
      was generally intermediate between the effects of blackout and the effects of
      reinforcement. These results are consistent with an interpretation of
      reinforcement omission effects in terms of the discriminative temporal control
      exerted by reinforcement and stimuli similar to it.

PMID- 16811626
TI  - Three-relay alternator circuit.

PMID- 16811627
TI  - Effects of alternative reinforcement: does the source matter?
AB  - In a chamber with a single response key, pigeon's key pecks were reinforced with
      food according to a variable-interval schedule. In addition, extra reinforcements
      occurred concurrently according to an independent schedule. In one condition,
      availability of the extra reinforcements was signalled by a change in key color
      from white to red. The extra reinforcements occurred after a peck on the red key.
      In a second condition, the extra reinforcements were unsignalled and occurred
      only after a 2-sec pause in pecking for one group of subjects and were
      unsignalled and occurred freely as scheduled for another group of subjects. In
      the first two conditions, duration of reinforcement was varied. A third condition
      duplicated the second but varied rate rather than duration of reinforcement. The
      rate of pecking varied inversely with the amount of extra reinforcement per unit
      time according to the same function, regardless of the condition regulating
      occurrence of the extra reinforcements, and regardless of whether or not a 2-sec
      pause was required for their occurrence. The shape of this function was predicted
      by Herrnstein's (1970) matching law.

PMID- 16811628
TI  - Time limits for completing fixed ratios. II. Stimulus specificity.
AB  - Pigeons were exposed to two stimuli that were each correlated with the same fixed
      ratio schedule. During one stimulus, the ratio had to be completed in more than a
      specified time for food to be presented. During the other, the ratio had to be
      completed in less than a specified time. Failures to meet the time criterion
      produced a timeout and reset the ratio. Treating the entire behavioral sequence
      generated by a fixed-ratio schedule as a unitary response and scheduling
      differential reinforcement with respect to the duration of the sequence produced
      effects comparable to those observed previously with individual responses. The
      times taken to complete the ratios conformed to the time criteria under both
      stimulus conditions. Similar effects have been observed with differential
      reinforcement of the duration of individual responses and in experiments
      specifying running speed criteria under discrete trial conditions.

PMID- 16811629
TI  - The effects of terminal-link fixed-interval and variable-interval schedules on
      responding under concurrent chained schedules.
AB  - Previous work using variable-interval schedules in the terminal links of
      concurrent chained schedules suggested that relative choice proportion in the
      initial links equalled relative rate of reinforcement in the terminal links. With
      fixed-interval terminal-link schedules, however, matching was not obtained. The
      present study held pairs of fixed-interval terminal-link schedules in a constant
      ratio but varied absolute sizes. Relative choice for the smaller terminal-link
      fixed-interval schedule was a negatively accelerated, increasing function of
      absolute size of the fixed-interval pairs. Matching was found only with the fixed
      interval pair of 5 and 10 sec. When pairs of variable-interval schedules were
      arranged so that the harmonic mean of the intervals equalled the fixed-interval
      parameter values, relative choice functions were like those for fixed-interval
      schedules.

PMID- 16811630
TI  - The Wyckoff observing response-a reappraisal.
AB  - Pigeons were trained on a Wyckoff observing response procedure in which key
      responses were reinforced on a mixed schedule consisting of fixed-interval and
      extinction components. In Experiment 1, stepping on a pedal (a) converted the
      mixed schedule to a multiple schedule, (b) replaced the mixed-schedule stimulus
      with an unlit key (or, in different phases, a blackout), or (c) had no
      consequence. In Experiment 2, pedal standing removed the mixed-schedule stimulus
      that was physically similar to the multiple-schedule stimuli or one that was less
      similar. In Experiment 3, Wyckoff's differential and nondifferential
      discrimination procedure was repeated. The results of Experiments 1 and 2 showed
      that the Wyckoff pedal response was controlled by neither the removal of the
      mixed-schedule stimulus nor the production of discriminative stimuli. The results
      indicated a correlation between key-response rates and pedal-standing time.
      Experiment 3 showed that high response rates to mixed-schedule stimuli were
      correlated with little pedal-standing time while high key-response rates to
      multiple-schedule stimuli were correlated with considerable pedal standing time.
      The correlation between key-response rates and pedal-standing time was related to
      the physical arrangement between the key and pedal operanda.

PMID- 16811631
TI  - Reinforcement values of visual patterns compared through concurrent performances.
AB  - Use of concurrent variable-interval performances confirms that more-complex
      visual patterns have greater reinforcement value for human subjects than less
      complex patterns. The findings tally with verbal evaluative ratings and with
      results of previous experiments using a discrete-trial binary-choice technique.

PMID- 16811632
TI  - Recognition by the pigeon of stimuli varying in two dimensions.
AB  - Pigeons served in four experiments, each of which involved about 44,000 discrete
      1.2-sec trials under steady-state conditions. The first experiment scaled a short
      segment of the visual wavelength continuum; this dimension was then combined in a
      conditional discrimination with each of three others; time after reinforcement,
      tone frequency, and line tilt. In the two-stimulus experiments, the birds'
      responses were reinforced in the presence of only one stimulus combination: "582
      nm" together with "2 min after reinforcement", "3990 Hz", or "vertical line".
      Many other stimulus combinations also appeared equally often and went without
      reinforcement. The wavelength stimuli conformed to an equal-interval scale, and
      per cent response was generally linear with wavelength, when scaled on cumulative
      normal coordinates. The components of the compound stimulus were found to
      interact in a multiplicative fashion; when one component differed greatly from
      its reinforcement value, changes in the other component had relatively little
      effect. For the "time"-"wavelength" compound, this interaction appeared to be
      modified by the effects of set or attention. Certain response latency data are
      reported, and other combination rules are discussed.

PMID- 16811633
TI  - Transitivity as a property of choice.
AB  - Pigeons' pecks in the presence of two concurrently available initial-link stimuli
      occasionally produced one of two stimuli associated with mutually exclusive
      terminal links. Pecks during either terminal link produced food according to
      aperiodic (variable-interval and variable-ratio) or periodic (fixed-interval and
      fixed-ratio) schedules of reinforcement. Aperiodic and periodic schedules to
      which the pigeons were indifferent, in the sense that these schedules maintained
      equal responding in the initial links, often yielded different preferences in
      separate choice tests with a third schedule. Conversely, aperiodic and periodic
      schedules that were equally preferred to a third schedule often failed to
      generate indifference. These intransitivities imply that (1) aperiodic and
      periodic schedules are not functionally equivalent in their effects upon choice,
      and (2) efforts to find a simple method for transforming aperiodic schedules into
      their periodic equivalents will fail.

PMID- 16811634
TI  - Second-order schedules: comparison of different procedures for scheduling paired
      and nonpaired brief stimuli.
AB  - Pigeons performed on a second-order schedule in which fixed-interval components
      were maintained under a variable-interval schedule. Completion of each fixed
      interval component resulted in a brief-stimulus presentation and/or food. The
      relation of the brief stimulus and food was varied across conditions. Under some
      conditions, the brief stimulus was never paired with food. Under other
      conditions, the brief stimulus was paired with food; three different pairing
      procedures were used: (a) a response produced the simultaneous onset of the
      stimulus and food; (b) a response produced the stimulus before food with the
      stimulus remaining on during food presentation; (c) a response produced the
      stimulus and the offset of the stimulus was simultaneous with the onset of the
      food cycle. The various pairing and nonpairing operations all produced similar
      effects on performance. Under all conditions, response rates were positively
      accelerated within fixed-interval components. Total response rates and Index of
      Curvature measures were similar across conditions. In one condition, a blackout
      was paired with food; with this different stimulus in effect, less curvature
      resulted. The results suggest that pairing of a stimulus is not a necessary
      condition for within-component patterning under some second-order schedules.

PMID- 16811635
TI  - Control of a continuous response dimension by a continuous stimulus dimension.
AB  - Pigeons were trained to respond to stimuli from a continuous stimulus dimension
      (tonal frequency) with response values from a continuous response dimension. Both
      the number of points of correspondence and problem difficulty were varied. After
      training, subjects were tested with stimulus values intermediate to those
      trained. During these test tones, subjects emitted only those response values
      reinforced during training. The study suggested that if there are fast and
      efficient methods to obtain control of a continuous response dimension by a
      continuous stimulus dimension, these methods must depend on factors other than
      simple generalization.

PMID- 16811636
TI  - The effect of discrimination training on responses to a new stimulus.
AB  - Most previous research on the effect of the duration of preceding discrimination
      training on responding to a new stimulus has measured the responding during
      extinction. To reduce effects originating in the extinction procedure itself, the
      present study assessed the effect of discrimination training on responses to a
      new negative stimulus added during continued discrimination training. Pigeons
      were given a new negative stimulus (blue key) after 0, 1, 3, or 9 days of
      discrimination training with a yellow key as the positive stimulus, and both a
      green key and a red key as negative. Fewer responses were made to the blue key
      when it was introduced after nine days of discrimination training than after less
      discrimination training. That effect of long discrimination training agrees with
      reported results from extinction tests. However, the effect of briefer
      discrimination training in the present study differed from reported results with
      extinction testing. It appears that testing during continued discrimination
      training eliminates a distortion present in extinction tests of the effect of
      discrimination training on responding to a new stimulus.

PMID- 16811637
TI  - Reinforcement of spaced responding in a simultaneous discrimination.
AB  - Pigeons were exposed to three stimuli simultaneously with responses reinforced
      according to differential-reinforcement-of-low-rate schedules. Responses to one
      stimulus (the positive stimulus) that were spaced appropriately resulted in food
      presentation. The variables manipulated were the time parameter of the schedule
      (5, 10, 20, 30 sec) and the consequences of responding to the other two stimuli
      (the negative stimuli). The percentage of the total responses that occurred to
      each stimulus was independent of the schedule value but was dependent on the
      consequences of responding to the negative stimuli. If responses to both reset
      the schedule timer, responding was confined largely to the positive stimulus. If
      responses to neither had scheduled effects, the birds were more likely to respond
      to those stimuli. Responding to one negative stimulus could be selectively
      attenuated by having responses to that stimulus alone reset the timer. With the
      schedule time value held constant, the absolute rate of responding to the
      positive stimulus was either stable or decreased with maintained exposure; it did
      not change as a function of increases or decreases in responding to the negative
      stimuli. Rather than interacting and affecting each other, responses to the three
      stimuli were controlled independently by their relation to reinforcement. There
      was no evidence that responses to the negative stimuli mediated the spacing of
      responses to the positive stimulus.

PMID- 16811638
TI  - Duration discrimination: effects of probability of stimulus presentation.
AB  - Monkeys initiated a stimulus by pressing on the center of three levers and the
      stimulus terminated independently of behavior 60, 80, 90, or 100 sec later.
      Presses on the right lever were reinforced with food following the three briefer
      durations, and presses on the left lever, following the 100-sec duration.
      Incorrect responses produced a 10-sec timeout. Probability of presenting the 100
      sec duration was manipulated in the range from 0.25 to 0.75, with the
      probabilities of the briefer durations remaining equal and summing to one minus
      the probability of the 100-sec duration. Percentage of responses on either side
      lever was functionally related to both the probability of presenting the 100-sec
      stimulus and to stimulus duration. An analysis of the data based on the theory of
      signal detection resulted in operating characteristics that were linear when
      plotted on normal-normal coordinates. The percentage of responses on either lever
      approximated the optimal values for maximizing reinforcement probability in each
      condition of the experiment.

PMID- 16811639
TI  - Reinforcement and response rate interaction in multiple random-interval avoidance
      schedules.
AB  - Two experiments were conducted to investigate the interaction between response
      rate and reinforcement frequency in multiple random-interval avoidance schedules.
      Responses cancelled delivery of shocks that could be scheduled at different
      random intervals in each component. When shock-frequency reduction was taken as
      the measure of reinforcement, the relationship between response rate and
      frequency of reinforcement was described by the same equations used by Herrnstein
      (1970) to describe responding with positive reinforcement.

PMID- 16811640
TI  - Punishment contras during free-operant avoidance.
AB  - Punishment of bar-pressing responses of rhesus monkeys with electric shock in one
      component of a multiple free-operant avoidance schedule suppressed responding in
      that component. These decreases were concomitant with response rate increases in
      the unpunished component (punishment contrast). Response rates in both components
      increased when punishment was removed and decreased in successive sessions. These
      effects of punishment on unpunished responding were similar to those obtained
      during single and multiple schedules of positive reinforcement and they suggest a
      further similarity in the development of discriminations during positive and
      negative reinforcement schedules.

PMID- 16811641
TI  - Lever attacking by rats during free-operant avoidance.
AB  - Rats pressed a lever to avoid shock on a free-operant avoidance schedule. Some
      subjects were also exposed to extinction in which the response-shock contingency
      was eliminated while the shock-shock contingency remained in effect. A specially
      constructed lever was used that registered not only presses, but also biting
      attacks on the lever. Throughout various phases of the study, shocks often
      elicited lever biting as well as post-shock responding. The results suggested
      that shock-elicited attacks that are forceful enough to activate the operandum
      might account for some of the responding that occurs in experiments on free
      operant avoidance behavior. In particular, shock-elicited operandum attacking
      might account for post-shock response bursting during free-operant avoidance and
      the extreme persistence of responding sometimes noted when shocks are delivered
      during the extinction of avoidance behavior. To the extent that this is true,
      these phenomena should not be characterized as operant behavior in interpreting
      the results of experiments on free operant avoidance.

PMID- 16811642
TI  - Response patterning on an avoidance schedule as a function of time-correlated
      stimuli.
AB  - Control of avoidance response patterning by time-correlated stimuli was studied
      in rhesus monkeys. At several shock-shock = response-shock intervals, the
      intervals were divided into 8, 4, or 2 time segments by correlating,
      respectively, 1, 2, or 4 discrete lights of an eight-light display with each
      successive segment. A further condition examined response patterning when the
      avoidance interval was not segmented: all eight lights of the display were lit
      throughout the interval. Reversal of the order in which the lights were lit in
      sequence was also examined. Generally, increasing the number of lights lit at one
      time (decreasing the number of signalled time segments) increased response rates
      and shifted interresponse time distributions to the left. When the lights were
      lit one at a time, signalling eight discrete time segments of the interval,
      response rates were consistently low.

PMID- 16811643
TI  - Combined-stimulus control as a function of the response rate controlled by the
      absence of the single stimuli.
AB  - Rat's bar-press responses were maintained at moderate rates during separate
      presentations of light and tone by separate but concurrent variable-interval
      schedules of food and shock presentation. The relative response rate maintained
      during light-out-no-tone was alternated in four successive phases: in Phases 1
      and 3 responding was maintained at a higher rate than that during light and tone
      alone by a variable-interval food schedule, while in Phases 2 and 4 responding
      was reduced to a lower rate by a differential-reinforcement-of-other-behavior
      food schedule. In test presentations of light, tone and a light-plus-tone
      combination, administered at the end of each phase, the proportion of responses
      emitted during light-plus-tone was an inverse function of the relative response
      rate controlled by light-out-no-tone, indicating that the relative training
      response rate controlled by the absence of the single stimuli determined the
      control exerted by the combined stimuli. Different relative response rates
      maintained in training may also be partly responsible for previously observed
      differences in the form of generalization gradients following the establishment
      of multi-stimulus control.

PMID- 16811644
TI  - Comparisons between variable-interval and fixed-interval schedules of electric
      shock delivery.
AB  - Responding maintained in rats under a variable-interval 35-sec food schedule was
      suppressed more by 60-sec and 240-sec fixed-interval schedules of shock delivery
      than by 60-sec and 240-sec variable-interval schedules of shock delivery. When
      the delivery of shock was preceded by a 5-sec visual stimulus, little overall
      response suppression was found with either fixed-interval or variable-interval
      schedules. In a third experiment, the percentage of occasions on which a cue
      preceded each shock delivery was varied from 0% to 100%. For the fixed-interval
      shock condition, the most suppression occurred with the 0% treatment, the least
      with 100%, and an intermediate amount with the 50% treatment. For the variable
      interval groups, the most suppression occurred in the 50% condition, the least in
      the 100% group, and an intermediate amount with 0%.

PMID- 16811645
TI  - Performance in concurrent fixed-interval schedules.
AB  - Six pigeons were trained on a variety of concurrent fixed-interval fixed-interval
      schedules. Matching between response or time ratios and ratios of obtained
      numbers of reinforcements was found for eight of 12 schedules studied. Cumulative
      records showed both typical burst-and-break patterns and also atypical response
      patterns in which response rate was constant between reinforcements on a
      schedule. Matching occurred only when the same pattern was present on both
      concurrent schedules. When different response patterns were generated by the two
      schedules, the pigeons consistently emitted fewer responses to the shorter fixed
      interval than required by matching.

PMID- 16811646
TI  - An analysis of response and time matching to reinforcement in concurrent ratio
      interval schedules.
AB  - Key pecks by six pigeons were reinforced on concurrent fixed-interval fixed-ratio
      schedules. The value of the fixed-interval was held constant at 4 min while the
      fixed-ratio varied from 25 to 450 responses. All of the pigeons responded on,
      with pecks reinforced under, both of the schedules over most of the concurrent
      pairings, and four of the six distributed responses between the schedules such
      that matching was obtained between the proportions of responses and
      reinforcements. Previous studies using concurrent variable-interval schedules
      have shown that when response-reinforcement matching occurs, a comparable match
      of time to reinforcement proportions is obtained. In the present study, time
      devoted to each response alternative was measured from the first response on that
      alternative to a subsequent response on the other alternative. Using that
      measure, large differences existed in the local rates of responding on the two
      schedules, and a time-reinforcement match was not produced. These results
      indicate that in a situation where response-reinforcement and time-reinforcement
      matching are incompatible, the measurement of response proportions is the better
      means of evaluating the effects of reinforcement.

PMID- 16811647
TI  - Contrast effects in maintained generalization gradients.
AB  - In Experiment I, pigeons were given equal reinforcement (variable-interval 1-min)
      for responding during randomized presentations of eight line-orientation stimuli.
      Then, only responding in the vertical orientation was reinforced. Stable
      generalization gradients soon formed and persistent behavioral and local
      (transient) contrast effects appeared. Local contrast effects were not a function
      of relative reinforcement frequency or of any other variable known to produce
      contrast. Instead, they were related to average response rates associated with
      each stimulus. Experiment II showed that local contrast effects represent
      increases and decreases in response rates relative to baseline responding, and
      that these effects are relative; a given stimulus might enhance responding during
      a subsequent presentation of one stimulus, but depress responding when followed
      by another. These data indicate that discrimination learning is not adequately
      described as the acquisition of excitatory properties by some stimuli and
      inhibitory properties by others. A more adequate account implies that stimuli
      exert both excitatory and inhibitory effects related to their value.

PMID- 16811648
TI  - Function of intertrial interval in matching-to-sample.
AB  - Twelve pigeons were trained on matching-to-sample using either a 0-, 5-, 15-, 25
      , or 60-sec intertrial interval. Eight of these 12 pigeons were given one of the
      following intertrial interval changes: 0 to 60, 0 to 5, 5 to 0, 60 to 0, 15 to
      25, 5 to 15, 60 to 5, 5 to 1, 1 to 5, 1 to 25, and 25 to 1 sec. Most intertrial
      interval changes were repeated at least once. The 0-sec intertrial interval
      subjects failed to match beyond chance levels, while other intertrial interval
      values resulted in matching acquisition. Changes from 0 sec to other intertrial
      interval values increased and changes to 0 sec decreased matching performance.
      Changes to intertrial interval values other than 0 sec resulted in little change
      in matching accuracy once stable performance had been attained.

PMID- 16811649
TI  - An inexpensive mechanism for programming multiple variable-interval schedules of
      reinforcement.

PMID- 16811650
TI  - Choice of longer or stronger signalled shock over shorter or weaker unsignalled
      shock.
AB  - Unsignalled, inescapable shocks were presented to four albino rats in one study
      and to six rats in a second study. By pressing a lever, subjects could change the
      condition to signalled shock for 3 min after which unsignalled shock was
      automatically reinstated. All subjects changed frequently to the signalled shock
      schedule. After a minimum of three 6-hr sessions or after changeover responding
      stabilized at the previous values, higher values of signalled shock intensity or
      duration were introduced. In the first study, the duration of signalled shock was
      increased in increments of 0.5 sec. In the second study, the intensity of
      signalled shock was increased in increments of either 0.2 or 0.4 mA. Duration
      subjects chose signalled shock four (2.0 sec) to nine times (4.5 sec) longer than
      unsignalled shock (0.5 sec). Intensity subjects chose signalled shock two (2.0
      mA) to three times (3.0 mA) more intense than unsignalled shock (1.0 mA).

PMID- 16811651
TI  - A rate measure of the relative aversiveness of signalled vs unsignalled shock.
AB  - Five rats were trained on a two-component multiple schedule with each component
      consisting of a two-link chain schedule. Differential response suppression in the
      initial links of the chain schedules was used as a measure of the relative
      aversiveness of events introduced into the subsequent terminal links. When
      unsignalled shock was scheduled in one terminal link and signalled shock in the
      other (in addition to equal numbers of food reinforcers), responding was
      suppressed to a greater degree in the initial link preceding the unsignalled
      shock condition. Reversing the terminal-link positions of unsignalled shock and
      signalled shock led to a reversal of the differential response suppression in the
      initial links. These results confirm previous findings that signalled shock is
      less aversive than unsignalled shock and extend the generality of this phenomenon
      from choice measures to rate measures of aversiveness.

PMID- 16811652
TI  - Pigeons respond to produce periods in which rewards are independent of
      responding.
AB  - Pecks by pigeons on a response key produced an ON state during which intermittent
      rewards were freely available, i.e., independently of responding. Pecks during
      the ON state caused it to remain ON. If no pecks occurred, the state changed to
      OFF-the key color changed-and rewards were not presented. The state remained OFF
      until the next response. Thus, responses controlled the state in the chamber but
      did not cause immediate reinforcement. Four dimensions of the schedule were
      varied: the rates of response-independent rewards during ON; the duration of ON
      produced by each peck; the pattern of rewards during ON; and the presence vs
      absence of exteroceptive cues during ON and OFF. The results showed that rates of
      responding were primarily controlled by the duration of ON produced by each
      response. When each response caused a long period of ON, pecks occurred
      infrequently; when each response caused a brief period of ON, pecks were
      frequent.

PMID- 16811653
TI  - Discrimination of a response-independent component in a multiple schedule.
AB  - Pigeons were trained to respond in non-differential reinforcement pre
      discrimination training, with a multiple variable-interval 1-min variable
      interval 1-min schedule. Each bird then received discrimination training with a
      multiple variable-interval 1-min variable-time 1-min schedule. Thus,
      discrimination training was between response-dependent (variable-interval) and
      response-independent (variable-time) schedules with the rate of reinforcement
      equated. In Experiment I, only three sessions of non-differential reinforcement
      preceded discrimination training and for half the birds, a 0 degrees line was
      correlated with the response-dependent schedule; for the remaining birds the 0
      degrees line was correlated with the response-independent schedule. Post
      discrimination gradients of excitatory stimulus control were obtained from the
      former group, while the latter group showed little evidence of post
      discrimination stimulus control by the 0 degrees line. Differential responding to
      the variable-time schedule was not accompanied by behavioral contrast to the
      variable-interval schedule. In Experiment II, 20 sessions of non-differential
      reinforcement preceded discrimination training and the 0 degrees line was
      correlated with variable-time reinforcement for each bird. Differential
      responding to the 0 degrees line was accompanied by negative induction to the
      variable-interval schedule and by inhibitory stimulus control about the 0 degrees
      line during a post-discrimination generalization test.

PMID- 16811654
TI  - The maintenance of key pecking by stimulus-contingent and response-independent
      food presentation.
AB  - Three naive pigeons were exposed to a series of two-component multiple schedules
      of response-independent food presentation. The component schedules were sometimes
      identical (non-differential procedures) and sometimes different (differential
      procedures). High rates of key pecking were maintained in all the differential
      procedures, and pecking decreased substantially in non-differential procedures,
      even when the frequency of food presentation in non-differential procedures was
      higher than in differential procedures. It is suggested that the high rates of
      key pecking were maintained not by adventitious response-reinforcer
      contingencies, but by differential contingencies between the stimulus (keylight)
      and food. The role of such contingencies in the phenomenon of behavioral contrast
      is discussed.

PMID- 16811655
TI  - The effect of the blackout method on acquisition and generalization.
AB  - In discrimination training with the Lyons' blackout method, pecks to the negative
      stimulus are prevented by darkening the chamber each time the subject approaches
      the negative stimulus. Stimulus generalization along a stimulus dimension was
      measured after training with this method. For comparison, generalization was also
      measured after reinforced responding to the positive stimulus without
      discrimination training, and after discrimination training by extinction of pecks
      to the negative stimulus. The blackout procedure and the extinction of pecks to
      the negative stimulus both produced a peak shift in the generalization gradients.
      The results suggest that after discrimination training in which the positive and
      negative stimulus are on the same continuum, the blackout method produces
      extinction-like effects on generalization tests.

PMID- 16811656
TI  - Redundant information in an observing-response procedure.
AB  - In three observing-response experiments relevant to the information hypothesis of
      conditioned reinforcement, the basic procedure was one in which an observing
      response produced one stimulus on trials that terminated in non-contingent
      reinforcement and another stimulus on trials that terminated in a brief timeout.
      In Experiment I, the observing response consisted of a single peck or a short
      fixed-ratio schedule (FR 3 or FR 6), depending on the type of trial. If the
      single peck produced the negative stimulus and the fixed ratio produced the
      positive stimulus, observing responses were maintained. If the single peck
      produced the positive stimulus and the fixed-ratio produced the negative
      stimulus, observing responses were not maintained on negative trials. In the
      second experiment, the response key was either white or dark at the beginning of
      a trial, indicating whether it was a positive or negative trial. Observing
      responses continued to be maintained on positive trials but not on negative
      trials. In Experiment III, only positive or negative trials were scheduled for
      several sessions. Observing responses extinguished regardless of whether positive
      or negative trials were scheduled. The results do not support the hypothesis that
      making the stimuli produced by observing responses redundant will reduce
      observing responses.

PMID- 16811657
TI  - Conditioned suppression of counting behavior in rats.
AB  - Three rats were trained on a schedule in which a response on lever B was
      reinforced only if it was preceded by a minimum number of consecutive responses
      on lever A. The minimum requirement was 27 A responses for Rat 1, and 20 A
      responses for Rats 2 and 3. The schedule maintained high rates of responding on
      lever A, and a slow, spaced pattern of responding on lever B. The mean number of
      consecutive responses on lever A was slightly greater than the minimum required.
      The effect of superimposing on this behavior a stimulus that ended with an
      unavoidable shock was the suppression of responding on both levers during the pre
      shock stimulus. Responses on lever A were more suppressed, and the proportion of
      relatively short response runs on lever A during the pre-shock stimulus
      increased. With all three rats, the mean number of consecutive responses on lever
      A during the pre-shock stimulus decreased to a value below the minimum
      requirement for reinforcement of the subsequent B response.

PMID- 16811658
TI  - Maintaining responding during stimulus generalization testing in extinction.
AB  - Resistance to extinction and generalization gradients were studied following
      training with a long-adjusting-interval schedule. One large reinforcer occurred
      at the end of each daily training session. Sessions varied in length from 20 sec
      to 42.66 min, but were usually the latter. Repeated generalization tests were
      subsequently conducted for these subjects and subjects trained with a more
      conventional short-random-interval schedule. The long-adjusting-interval schedule
      produced generalization gradients that were not qualitatively different from
      those produced by the conventional procedure. However, the advantages of the long
      adjusting-interval schedule are: (1) greater resistance to extinction both within
      and across generalization tests and (2) more stable gradient slopes within and
      across tests.

PMID- 16811659
TI  - Nondiscriminated avoidance of shock by pigeons pecking a key.
AB  - Four pigeons were trained to avoid shock by pecking a key on a free-operant
      avoidance schedule in which no exteroceptive stimulus signalled impending shock.
      Response rate was an inverse function of response-shock interval when shock-shock
      interval was held constant at 2 sec and response-shock intervals varied from 5 to
      40 sec. Amphetamine increased response rates in two subjects and reserpine
      markedly reduced responding in one.

PMID- 16811660
TI  - Application of Bower's one-element model to paired-associate learning by pigeons.
AB  - Bower's (1961) all-or-none model of human paired-associate learning was applied
      to individual data supplied by three pigeons. When the center one of three keys
      was illuminated with red light or with three white dots in a vertical array on a
      black ground, pecking on the left key was reinforced. When the center key was
      lighted green or with a horizontal array of three white dots on a black ground,
      pecking on the right key was reinforced. The left and right keys were illuminated
      with white light. The task was considered to be analogous to learning a paired
      associate list of four pairs involving four stimulus items and two response
      items. The model was evaluated by comparing the following model predictions with
      values obtained from each animal: trials-to-criterion, standard deviation of
      trials-to-criterion, standard deviation of errors-to-criterion, mean error runs,
      mean error runs of lengths one to four, and autocorrelations of errors of lags
      one to three. Most of the predictions based upon the model were in close
      agreement with the obtained data.

PMID- 16811661
TI  - Associative factors underlying the pigeon's key pecking in auto-shaping
      procedures.
AB  - Key pecking in pigeons can be engendered by associating response-independent food
      presentations with illumination of a key. Specific pairings of key and food are
      not necessary for this phenomenon. Differential positive association between key
      and food (defined in terms of relative densities of reinforcement), however, is
      necessary and sufficient to produce and maintain key pecking. Thus, the
      occurrence of key pecking in auto-shaping can be considered to depend on
      associative processes similar to classical conditioning. Consequently, auto
      shaped pecking can be virtually eliminated by the addition of food presentations
      in the intertrial interval, thus removing the association between key and food.
      Initial exposure to random reinforcement, or reinforcement only in the absence of
      the key, results in lower rates of pecking in subsequent auto-shaping procedures.

PMID- 16811662
TI  - Responding under chained and tandem fixed-ratio schedules.
AB  - The role of stimuli in chained fixed-ratio schedules of reinforcement was
      examined. At various ratio values, responding on schedules consisting of three or
      five equal components, with a different colored light in each component ("block
      counter") was compared with responding on tandem or simple fixed-ratio schedules
      having the same color present throughout the entire ratio. At all ratio values
      except the smallest, the chain stimuli resulted in longer pauses after
      reinforcement. The magnitude of this effect became greater as the size of the
      ratio was increased. Post-reinforcement pause durations were longer under five
      component schedules than under three-component schedules. Running rates in the
      first component were lower on the chained schedules than on the tandem schedules;
      on both kinds of schedule, rates were lower in the first component than in the
      rest of the ratio. When the sequence of stimuli was reversed, the duration of the
      post-reinforcement pause dropped markedly and the running rate in the initial
      component increased, but these effects gradually disappeared after the first
      reversal session. When the final chain stimulus was substituted for the first
      component stimulus but continued to appear in the final chain component as well,
      the pause duration dropped and remained at this lower level during subsequent
      sessions.

PMID- 16811663
TI  - Self-imposed timeouts under increasing response requirements.
AB  - Self-imposed timeouts by pigeons working under a progressive-ratio food schedule
      were studied under different conditions. The main findings were (1) continued
      production of timeouts over an extended series of sessions, (2) more frequent
      responding on the key with the timeout consequence than on a key having no
      consequence, (3) an inverse relationship between number of timeouts and level of
      body weight, (4) production of timeouts when the timeout duration was brief,
      lengthy, or controlled by the pigeon, and (5) dependence of self-imposed timeouts
      on variables controlling responding under the progressive-ratio schedule. Under
      all experimental conditions, with the exception of performances at the high body
      weight, timeouts were more frequent during the longer progressive-ratio steps and
      usually were localized in the post-reinforcement pause or the early part of the
      step. The timeout behavior could be interpreted as either an escape from aversive
      stimuli generated by the progressive-ratio schedule or as a response reinforced
      by the consequent stimulus change.

PMID- 16811664
TI  - Piezoelectric pecking key.

PMID- 16811665
TI  - Response decrements produced by extinction and by response-independent
      reinforcement.
AB  - The effects of extinction and of response-independent (free) reinforcement in
      decreasing rates of key pecking by pigeons were compared in single schedule
      (Phase 1) and multiple (Phase 2) conditions. In both phases, response rates
      decreased more rapidly with extinction than with free reinforcement conditions.
      Behavioral contrast was obtained from subjects trained in a multiple schedule
      involving extinction in Phase 2, whereas subjects trained in a multiple schedule
      involving free reinforcement showed a slight negative induction effect. Whether
      subjects experienced extinction or free reinforcement under single stimulus
      conditions did not affect subsequent performance in the discrimination situation
      of the second phase. Disinhibition testing was carried out at the end of both
      phases, but there was no evidence for disinhibitory effects under any condition.

PMID- 16811666
TI  - Stimulus generalization and delay of reinforcement during one component of a
      multiple schedule.
AB  - The key pecking of six pigeons was reinforced according to a variable-interval 1
      min schedule during each of two successively presented stimuli. When the key was
      illuminated by a black line on a white background, reinforcement was delayed for
      10 sec. When the key was illuminated by a plain white light, reinforcement was
      not delayed. All subjects responded at a lower rate during the presentation of
      the black line. A subsequent generalization test along the line-orientation
      dimension produced a U-shaped gradient, with the nadir located at or near the
      training stimulus, for each subject. These gradients suggested that the lower
      rate of response during the stimulus associated with delayed reinforcement may
      have been due to an inhibition of responding.

PMID- 16811668
TI  - Choice between concurrent schedules.
AB  - Six pigeons pecked for food in a three-key experiment. A subject at any time
      could choose the left or right key and receive reinforcement according to one two
      key concurrent variable-interval variable-interval schedule of reinforcement, or
      it could peck the center key. A peck on the center key arranged the complementary
      two-key concurrent variable-interval variable-interval schedule on the left and
      right keys. The two different two-key concurrent schedules arranged
      reinforcements concurrently and were signalled by two different colors of key
      lights. Choice behavior in the presence of a given color conformed to the usual
      relationship in two-key concurrent schedules: the relative frequency of
      responding on a key approximately equalled the relative frequency of
      reinforcement on that key. Preference for a two-key concurrent schedule, which
      was equivalent to preference for a color, was measured by the percentage of all
      responses on the left and right keys in the presence of that color: this
      percentage approximately equalled the percentage of all reinforcements that were
      delivered in the presence of that color. Thus, choice between concurrent
      schedules conforms approximately to the same relationship as does choice between
      alternatives in a single concurrent schedule.

PMID- 16811667
TI  - Synthetic variable-interval schedules of reinforcement.
AB  - Three pigeons pecked for food on a synthetic variable-interval schedule of
      reinforcement that had two independent parts: a variable-interval schedule that
      arranged a distribution of interreinforcement intervals, and a device that
      randomly assigned each reinforcement to one of 10 classes of interresponse times.
      The frequencies of reinforcement for the 10 classes of interresponse times were
      systematically varied, while the overall frequency of reinforcement was held
      within a comparatively narrow range. The 10 classes extended either from 0.1 to
      0.6 sec in 0.05-sec intervals, or from 1.0 to 6.0 sec in 0.5-sec intervals. In
      the former case, some control by reinforcement was obtained, but it was weak and
      no simple relationships were discernible. In the latter case, the relative
      frequency of an interresponse time was a generally increasing function of its
      relative frequency of reinforcement, and two simple controlling relationships
      were found. First, the function relating interresponse times per opportunity to
      reinforcements per opportunity was, over a restricted range, approximately linear
      with a slope of unity. Second, when all 10 classes of interresponse times were
      reinforced equally often, the relative frequency of an interresponse time
      approximately equalled the relative reciprocal of its length.

PMID- 16811669
TI  - Avoidance conditioning with shock contingent upon the avoidance response.
AB  - Rats learned either a lever-press response, a shuttle response or a one-way
      crossing response, which produced one immediate shock but was instrumental in
      avoiding five identical shocks scheduled to occur later. These responses were
      acquired both with and without support of an escape contingency. These results
      support shock-frequency reduction as a sufficient condition for the acquisition
      and maintenance of avoidance.

PMID- 16811670
TI  - Stimulus control and auditory discrimination learning sets in the bottlenose
      dolphin.
AB  - The learning efficiency of an Atlantic bottlenose dolphin was evaluated using
      auditory discrimination learning-set tasks. Efficiency, as measured by the
      probability of a correct response on Trial 2 of a new discrete-trial, two-choice
      auditory discrimination problem, reached levels comparable to those attained by
      advanced species of nonhuman primates. Runs of errorless problems in some cases
      rivaled those reported for individual rhesus monkeys in visual discrimination
      learning-set tasks. This level of stimulus control of responses to new auditory
      discriminanda was attained through (a) the development of a sequential within
      trial method for presentation of a pair of auditory discriminanda; (b) the
      extensive use of fading methods to train initial discriminations, followed by the
      fadeout of the use of fading; (c) the development of listening behavior through
      control of the animal's responses during projection of the auditory
      discriminanda; and (d) the use of highly discriminable auditory stimuli, by
      applying results of a parametric evaluation of discriminability of selected
      acoustic variables. Learning efficiency was tested using a cueing method on Trial
      1 of each new discrimination, to allow the animal to identify the positive
      stimulus before its response. Efficiency was also tested with the more common
      blind baiting method, in which the Trial 1 response was reinforced on only a
      random half of the problems. Efficiency was high for both methods. The overall
      results were generally in keeping with exceptations of learning capacity based on
      the large size and high degree of cortical complexity of the brain of the
      bottlenose dolphin.

PMID- 16811671
TI  - Schedule-induced mirror responding in the pigeon.
AB  - Two pigeons that were previously exposed to a multiple schedule of reinforcement
      in the presence of a stuffed and a live pigeon, and two of three naive pigeons,
      responded on a mirror during exposure to multiple fixed-ratio, fixed-ratio
      schedules of reinforcement for key pecking. Both the topography and temporal
      pattern of mirror responding were comparable to schedule-induced "attack" on live
      and stuffed targets. Rate of target responding was reduced when either the mirror
      was covered with paper or when the multiple schedule was removed. A reversal in
      the relationship between reinforcement schedules and discriminative stimuli
      demonstrated that mirror responding was controlled by the stimulus correlated
      with the higher fixed-ratio schedule. With one component of the multiple schedule
      held constant at fixed ratio 25 and the ratio requirement of the other component
      varying from 25 to 150, there was an inverted U-shaped relationship between rate
      of mirror responding and fixed-ratio schedule in the varied component. As in
      Flory's study (1969b) there was an inverted U-shaped relationship between target
      responding and inter-food intervals. The combined results of these studies
      suggest that the relationship between rate of target responding and reinforcement
      schedules is controlled primarily by the inter-food intervals resulting from the
      schedules.

PMID- 16811672
TI  - Audit responses: responses maintained by access to existing self or coactor
      scores during non-social, parallel work, and cooperation procedures.
AB  - Human subjects, mostly between 11 and 16 yr old, matched to sample for points
      that were exchangeable for money. An audit response was defined as a response
      maintained by allowing a subject access to an existing score on his own (self
      audit) or a coactor's (coactor audit) performance. In Experiment I, changes from
      non-social procedures (no coactor) to social procedures (coactor present)
      increased self and coactor audits. Since both types of audits occurred at about
      the same rates during cooperation and parallel work procedures, the increases did
      not depend on the subjects' response interactions. Although Experiment I did not
      demonstrate that subjects were comparing scores, the frequent occurrence of each
      kind of audit within a brief time period (interpersonal audit) did indicate that
      it was reinforcing to have both scores at the same time. These interpersonal
      audits suggested that the coactor's score increased self audits during social
      procedures. Experiment II supported this notion: relative to a non-social
      procedure, self audits increased more during a parallel work procedure when the
      coactor's score was accessible than when it was not accessible. Thus, increases
      in other behaviors that occur in the presence of a coactor, i.e., social
      facilitation, may also result from or be increased by providing a coactor's
      score.

PMID- 16811673
TI  - Effects of choice and immediacy of reinforcement on single response and switching
      behavior of children.
AB  - Children responded on a single operandum to produce marbles or candy within a two
      component multiple schedule and then were allowed to choose which component was
      in effect. Experiment I examined the effects of exchanging marbles after sessions
      for subject-selected or experimenter-selected candy. Rate of response to the
      single operandum was not affected. However, when the subjects could switch
      components, they spent the majority of time and responded at somewhat higher
      rates in a component where marbles were exchangable for subject-selected candy.
      Experiment II examined the effects of eliminating the immediate marble
      consequence for responses. Rate of response to the single operandum was not
      affected. However, when subjects could switch components they spent more time in
      a component where immediate marble consequences were available for responses,
      than where no immediate marble consequences were available.

PMID- 16811674
TI  - Relative delay of reinforcement and choice.
AB  - Pigeons' responses on either of two concurrently available keys each associated
      with variable-interval 60-sec schedules occasionally changed the schedule on that
      key to a terminal-link interval schedule providing access to gain while the other
      key became inoperative. Experiment I compared simple fixed- and mixed-interval
      schedules in the terminal links, and showed that for all subjects and schedules
      the distribution of responses during the concurrent initial links was accurately
      described by the relative inverse delay of reinforcement squared. Experiment II
      extended the generality of this formulation to a situation in which rate of
      reinforcement was constant and delay alone was varied.

PMID- 16811675
TI  - Interaction of frequency and magnitude of reinforcement on concurrent
      performances.
AB  - Frequency and magnitude of reinforcement were varied in concurrent variable
      interval variable-interval schedules of reinforcement. The relative response rate
      to the two stimuli did not support the notion that choice approximately matches
      relative total access to food (the product of frequency and magnitude of
      reinforcement in one schedule divided by the sum of products of frequency and
      magnitude in both schedules). Relative response rates matched relative
      reinforcement value when that measure was adjusted to give more emphasis to
      reinforcement frequency than to reinforcement duration.

PMID- 16811676
TI  - Behavioral aftereffects of reinforcement and its omission as a function of
      reinforcement magnitude.
AB  - Rats responded on a multiple fixed-interval fixed-interval schedule of
      reinforcement. Each complete cycle of the multiple schedule was separated from
      the next by a relatively long period of timeout from all schedule contingencies.
      A response at the end of the second component of each cycle was always reinforced
      with an invariant reinforcement magnitude, while reinforcement magnitude and
      reinforcement omission were systematically varied in the first component.
      Response rate in the first component was a monotonic function of reinforcement
      magnitude in that component. These changes in response rate in the first
      component did not affect response rate in the second component. When
      reinforcement was omitted on 50% of occasions in the first component, following
      reinforcement there was a reduction in response rate in the second component that
      was monotonically related to reinforcement magnitude. Following reinforcement
      omission there was an increase in response rate in the second component that was
      unrelated to reinforcement magnitude. When reinforcement was omitted on 100% of
      occasions in the first component, behavioral contrast was observed.

PMID- 16811677
TI  - Facilitation and suppression of responding under temporally defined schedules of
      negative reinforcement.
AB  - Two parameters for scheduling aversive stimulus presentations were studied
      systematically by specifying concurrent and independent probabilities of electric
      shock delivery for the occurrence and for the non-occurrence of a lever-press
      response. After preliminary training on a free-operant shock-avoidance schedule,
      16 rhesus monkeys were divided into four groups, each group being assigned one
      shock distribution on a continuum from fixed interval to a widely ranging
      variable interval. Within groups, each subject was successively exposed to three
      values of response-dependence of shock delivery on a continuum from response
      independent shock to complete dependence of shock on response occurrence
      ("punishment"). Introduction of shock following avoidance training produced
      initial response facilitation followed by suppression. Responding during both the
      facilitation and suppression periods was maximal when the shock schedule was
      periodic and response independent. Responding decreased as the inter-shock
      intervals were made more variable across groups, and as shock delivery was made
      increasingly response dependent within individual subjects.

PMID- 16811678
TI  - Shock intensity and duration interactions on free-operant avoidance behavior.
AB  - Shock intensities (1 to 4 mA) and shock durations (0.3 to 0.75 sec) were
      concurrently varied over a range commonly used in free-operant avoidance studies
      using a lever-press response. Response rates were a positive linear function of
      the log of the product of intensity times duration. Shock rates were a negative
      linear function of that log. The increase in response rates was primarily due to
      a selective increase in the conditional probability of making responses with long
      interresponse times. The disproportionality of receiving shocks early in the
      session (warm-up) was also a linear function of the log of the intensity-duration
      product, with increasing disproportionality as the value of the intensity
      duration product was increased. Thus, with all measures of the avoidance
      performance, shock intensity and shock duration combine in a multiplicative
      fashion to determine the avoidance performance.

PMID- 16811679
TI  - Sequential dependencies in free-responding.
AB  - Three pigeons pecked for food in an experiment in which reinforcements were
      arranged for responses terminating sequences of interresponse times. Each
      reinforced interresponse time belonged to a class extending either from 1.0 to
      2.0 sec (class A) or from 3.0 to 4.5 sec (class B). Reinforcements were arranged
      by a single variable-interval schedule and a random device that assigned each
      reinforcement to one of four sequences of two successive interresponse times: AA,
      AB, BA, or BB. Throughout the experiment, half of the reinforcements were
      delivered for interresponse times in class A and half for those in class B. Over
      conditions, the interresponse time preceding a reinforced interresponse time
      always, half of the time, or never, belonged to class A. The duration of the
      interresponse time preceding a reinforced one had a pronounced effect on response
      patterning. It also had a pronounced effect on the overall response probability,
      which was highest, intermediate, and lowest, when the interresponse time
      preceding a reinforced interresponse time always, half of the time, or never,
      belonged to class A, respectively. In no case were successive interresponse times
      independent, so that overall response probability was not representative of
      momentary response probabilities.

PMID- 16811680
TI  - Behavioral contrast with timeout, blackout, or extinction as the negative
      condition.
AB  - When either a timeout period (darkening the response key) or a blackout period
      (darkening both chamber and response key) was alternated with a stimulus
      associated with variable-interval reinforcement, behavioral contrast was
      obtained. Either peck contrast or maintained contrast occurred, depending on
      whether or not responding was evidenced during the negative condition. These
      results are contrary to recent accounts emphasizing the role of non-reinforced
      responding in the production of contrast, but are consistent with interpretations
      emphasizing the aversiveness of the negative condition.

PMID- 16811681
TI  - Key pecking under response-independent food presentation after long simple and
      compound stimuli.
AB  - Sixteen pigeons were trained to peck a key using a response-independent (auto
      shaping) procedure of food presentation. The 4-sec grain presentations were
      independent of responding but a keylight stimulus preceded each, with a 4-min
      interval between the grain presentation and the next stimulus. Subjects were
      divided into four groups, with two durations of the keylight (30 or 120 sec) and
      either one or four successive colors on the response key preceding food delivery.
      In Phase 2, the birds were continued with the same keylight duration but were
      presented the alternative number of key colors. All pigeons pecked the key during
      the stimulus. Birds in the two groups with the 30-sec stimulus duration began to
      respond significantly sooner than birds with the 120-sec duration. There were no
      significant differences in rate of pecking between groups by the last five days
      of Phase 1. In Phase 1, the pigeons exposed to the four stimulus components
      showed an increase in rate of pecking over the four components as grain
      presentation approached. The pigeons with one stimulus component did not exhibit
      this regularity. Analogous conditions in Phase 2 had similar results except for
      one group. The implications of the occurrence of key pecking due to response
      independent food delivery for multiple and chained schedules were pointed out.

PMID- 16811682
TI  - Self-inhibiting effects of reinforcement.
AB  - The reinforcers produced by one response reduce the rate of other, concurrently
      reinforced responses. An analysis of the logical and empirical implications of
      the relation indicates that one reinforcer must have this effect on responses
      maintained by other reinforcers even when all reinforcers are produced by the
      same class of responses. A quantitative expression of the relation leads to a
      formulation, mathematically equivalent to Herrnstein's (1970), in which the rate
      of a reinforced response is a joint function of (1) an excitatory effect of the
      reinforcers produced by that class of responses, and (2) an inhibitory effect of
      the total reinforcers produced both by that class and by other classes of
      responses.

PMID- 16811684
TI  - An inexpensive feeder for rapid delivery of monkey pellets.

PMID- 16811683
TI  - A note on Herrnstein's Equation.

PMID- 16811685
TI  - An operant discrimination task allowing variability of reinforced response
      patterning.
AB  - Five pigeons were trained to perform a discrimination task allowing variability
      of reinforced response patterning. The task consisted of moving a stimulus light
      within an 4x4 matrix of lights from the top left position to the bottom right
      position by pecking on two keys in succession in order to obtain a reinforcement.
      A peck on one key moved the light one position to the right and a peck on the
      other key moved it one position down. After preliminary training on alternating
      fixed-ratio 3 schedules of reinforcement, the birds could peck on either key in
      any order, but more than three responses on a key resulted in a blackout followed
      by the return of the stimulus light to the start position. Results indicate that
      initially the birds used a wide variety of response patterns to obtain
      reinforcement, but with continued practice, response patterns became more
      stereotyped.

PMID- 16811686
TI  - Continuous, fixed-ratio, and fixed-interval reinforcement in honey bees.
AB  - Bees learned to enter a Plexiglas tube and to suck small portions of sugar
      solution; every entry or every fifth entry was reinforced. During an extinction
      phase, the bees on the fixed-ratio schedule emitted twice as many responses as
      did those given continuous reinforcement. Bees on a fixed-interval schedule of
      reinforcement emitted lower response rates than did those given fixed-ratio
      reinforcement. By extending the conditioning procedure for several days, it was
      possible to maintain responding with fixed-ratio schedules requiring 30 responses
      per reinforcement and with fixed-interval values up to 90 sec. Under fixed
      interval schedules, response rates did not increase toward the end of the
      reinforcement intervals.

PMID- 16811687
TI  - The correlation-based law of effect.
AB  - It is commonly understood that the interactions between an organism and its
      environment constitute a feedback system. This implies that instrumental behavior
      should be viewed as a continuous exchange between the organism and the
      environment. It follows that orderly relations between behavior and environment
      should emerge at the level of aggregate flow in time, rather than momentary
      events. These notions require a simple, but fundamental, change in the law of
      effect: from a law based on contiguity of events to a law based on correlation
      between events. Much recent research and argument favors such a change. If the
      correlation-based law of effect is accepted, it favors measures and units of
      analysis that transcend momentary events, extending through time. One can measure
      all consequences on a common scale, called value. One can define a unit of
      analysis called the behavioral situation, which circumscribes a set of values.
      These concepts allow redefinition of reinforcement and punishment, and
      clarification of their relation to discriminative stimuli.

PMID- 16811688
TI  - A technique for programming long interval schedules.

PMID- 16811689
TI  - Maintenance of key pecking by response-independent food presentation: the role of
      the modality of the signal for food.
AB  - Three pigeons were exposed to a series of procedures in which periods of response
      independent food presentation, on a variable-time schedule, alternated with
      periods in which food was never presented. The stimuli that signalled periods of
      food availability or non-availability varied from one procedure to the next, and
      were sometimes key colors, sometimes tones, and sometimes compounds of both. Key
      pecking was initiated and maintained when key color was a signal for food; key
      pecking was not initiated when a tone was the signal for food. However, control
      of key pecking that was already established could be transferred from key color
      to tone, and subsequently, initiated by the tone. It is suggested that for
      pigeons, pre-experimental relationships exist among food, visual stimuli, and
      pecking, and that a similar relationship, which includes auditory stimuli, must
      be induced in the laboratory.

PMID- 16811690
TI  - The failure of stimulus control after presence-absence discrimination of click
      rate.
AB  - Pigeons were trained to discriminate a slow click-rate from its absence, or to
      discriminate it from a faster click-rate. Subsequent click-rate generalization
      tests produced the usual steepened gradients after the intradimensional
      discrimination but produced flat gradients after presence/absence discrimination.
      The occurrence of stimulus control only after intradimensional discrimination,
      combined with previous results showing stimulus control sometimes after
      nondifferential reinforcement and sometimes after presence/absence
      discrimination, argues for a reformulation of the problem of stimulus control. A
      theoretical framework, relying upon blocking effects inherent in the different
      discrimination procedures, was presented to account for the diversity of results.

PMID- 16811691
TI  - A bifunctional pulse former.

PMID- 16811692
TI  - Signalled reinforcement in multiple and concurrent schedules.
AB  - Five pigeons were exposed to multiple and concurrent variable-interval, variable
      interval reinforcement schedules in which reinforcement availability in one
      component was never signalled. During certain phases of the experiment,
      reinforcement availability in the other component was signalled. Behavioral
      contrast was observed in seven of eight instances when reinforcement availability
      in the multiple schedules was signalled. Under the concurrent schedules in which
      reinforcement availability was signalled, the subjects did not always allocate
      more time to (prefer) the component containing non-signalled reinforcement, as
      would be predicted by an account of behavioral contrast holding that contrast
      results from the introduction of a less-preferred condition in one component of a
      multiple schedule.

PMID- 16811693
TI  - The relative aversiveness of signalled versus unsignalled shock-punishment.
AB  - Six rats were trained on a two-component multiple schedule with each component
      consisting of a two-link chain schedule. Differential response suppression in the
      two initial links, as well as in the two terminal links of the chain schedules,
      was used as a measure of the relative aversiveness of stimulus events in the two
      terminal links. When signalled and unsignalled shock-punishment (in addition to
      equal numbers of food reinforcers) were scheduled in the separate terminal links,
      subjects responded at lower rates in the initial link preceding unsignalled shock
      punishment than in the initial link preceding signalled shock-punishment.
      Similarly, subjects responded at lower rates in the terminal link containing
      unsignalled shock-punishment than in the terminal link containing signalled shock
      punishment. Reversing the terminal-link positions of signalled and unsignalled
      shock-punishment led to a reversal of the differential response suppression in
      the two initial and the two terminal links of the chain schedules. These results
      indicate that signalled punishment is relatively less aversive than unsignalled
      punishment and support an "information hypothesis", which assumes that a
      condition in which information is provided about the onset of environmental
      events, even negative events such as shock punishment, is more reinforcing than a
      condition in which such information is absent.

PMID- 16811694
TI  - Choice of higher density signalled shock over lower density unsignalled shock.
AB  - Unsignalled, inescapable shocks were presented to four albino rats in Experiment
      1. By pressing a lever subjects could change the condition to signalled shock for
      3-min periods after which unsignalled shock was automatically reinstated. All
      subjects changed from unsignalled to signalled shock when shock density was the
      same or when the density of signalled shock was two times greater than
      unsignalled shock. When the density of signalled shock was four times that of
      unsignalled shock, three subjects changed to the higher density schedule. One
      subject changed to a density of signalled shock eight times that of unsignalled
      shock. The second study showed that the two shock schedules most similar in
      Experiment 1 were discriminably different because subjects chose lower over
      higher shock densities when both densities were unsignalled. An analysis
      stressing safe (signal absent) and unsafe (signal present) periods was discussed.

PMID- 16811696
TI  - An inexpensive food-peck recorder for pigeons.

PMID- 16811695
TI  - Compounding of discriminative stimuli that maintain responding on separate
      response levers.
AB  - In Experiment 1, rats' responses were reinforced on a fixed-interval 30-sec
      schedule in the presence of either a light or a tone and were not reinforced in
      their absence. Each stimulus was correlated with its own response lever, with
      only one lever present during a session. When light and tone were compounded in
      the presence of the tone-correlated lever, no change in responding occurred.
      However, when tone was compounded with light in the presence of the light
      correlated lever, level of responding was greater than to light alone (response
      summation). Summation was also found when each stimulus was correlated with the
      same lever. Next, light and tone were again correlated with separate levers, but
      both levers were always simultaneously present. Compounding produced both
      summation and emission of most responses on the light-correlated lever. This
      prepotency of light was reduced (1) by leaving a houselight on throughout the
      session; and (2) by correlating each stimulus with a different schedule (either
      fixed-interval 4.7-sec or fixed-interval 30-sec). With a medium- and high
      intensity houselight and with the different reinforcement schedules, similar
      results were obtained during compounding, regardless of whether compounding
      occurred in the presence of the light- or tone-correlated lever.

PMID- 16811697
TI  - Effects of two procedures for varying information transmission on observing
      responses.
AB  - Two experiments were conducted with pigeons to examine the effects of procedures
      that varied information transmission on observing responses. The basic procedure
      for Experiment I was one in which a trial terminated in either non-contingent
      reinforcement or timeout. Pecking during a trial produced either green (positive)
      or red (negative) keylights. If no pecking occurred no differential stimuli
      appeared. The probability of positive trials was either 0.25, 0.50, or 0.75.
      Observing response rates and relative frequencies of occurrence were highest when
      the probability of positive trials was 0.25 and lowest at 0.75. In Experiment II,
      a modified chain procedure was used in which responding produced either red or
      green lights. Reinforcement or timeout followed light onset by 15 sec. The
      correlation between the stimuli and the event at the end of the trial
      (reinforcement or timeout) was varied. Reinforcement followed green 100%, 90%,
      70%, or 50% of the time that green occurred. Since the overall probability of
      reinforcement remained at 0.50, reinforcement followed red in either 0%, 10%,
      30%, or 50% of the time that it occurred. The rate of responses that produced
      these stimuli varied as a function of the correlation. The greater the
      probability of reinforcement after green, the higher the response rate.

PMID- 16811698
TI  - Extinction-induced aggression during errorless discrimination learning.
AB  - Pigeons were trained to discriminate without errors between a green light and a
      dark key. The key-pecking response was reinforced in the presence of green, and
      extinction was in effect in the presence of the dark key. The duration of the
      dark key was gradually increased during the first few sessions of conditioning.
      The opportunity to attack a restrained target pigeon was also present. During
      discrimination training, the rate of attack in the presence of the dark key was
      higher for each animal than the operant level, even though most of the animals
      acquired the discrimination without errors. Furthermore, the rate of attack did
      not decrease during 45 sessions of discrimination training. Attack also occurred
      in the presence of the green stimulus, although to a lesser extent than during
      extinction. Reinforcement during green is a determinant of attack during
      extinction because removal of reinforcement virtually eliminated attack during
      extinction.

PMID- 16811699
TI  - Observing stimulus sources that signal food or no food.
AB  - Pigeons were given a choice between observing a stimulus source that was
      uncorrelated with food or one that was informative. The informative source was
      either positive, in which a stimulus change signalled food, or negative, in which
      change signalled no food. If observing is supported by the reduction of
      uncertainty, the negative as well as the positive source should be preferred to
      the uncorrelated source. On the other hand, if observing requires support by
      conditioned reinforcement, the negative source should not be preferred to the
      uncorrelated source. Two keys served as stimulus sources in a discrete trial
      procedure. The keys were lighted together, remained on for a variable length of
      time, and went off together. A key could change color 1 sec before going off. In
      the uncorrelated source, the change occurred equally often on trials ending with
      or without food. In the positive information source, the change occurred only on
      food trials, whereas in the negative information source, it occurred only on no
      food trials. All stimulus changes and food delivery were response independent. As
      measured by orientation and autoshaped pecking, the positive information source
      was preferred to the uncorrelated source. However, the uncorrelated source was
      preferred to the negative information source. The latter result does not support
      the view that observing behavior is reinforced by the reduction of uncertainty.
      The positive and negative information sources reduced uncertainty equally but
      only the positive source provided a signal that could act as a conditioned
      reinforcer by virtue of its relation to food.

PMID- 16811700
TI  - Steady state responding based upon simple and compound stimuli.
AB  - Two pigeons were trained to perform discrimination tasks along two dimensions,
      wavelength of a circular spot of light and orientation of a white line.
      Discriminability among stimuli along these dimensions was established for both
      subjects by means of a steady state testing procedure. The two dimensions were
      then combined by superimposing the white line upon the colored background.
      Subjects were given a series of tests in which a correct response could be made
      on the basis of either of the two components of the stimulus compounds.
      Discriminability among these redundant compound stimuli was found to be better
      than that among wavelength and tilt stimuli alone. A second series of tests was
      administered using both redundant and conflicting compound stimuli. The results
      of this test series are consistent with a response strategy in which subjects
      first examine both elements of a compound and then emit a choice response on the
      basis of the element that best predicts reinforcement.

PMID- 16811701
TI  - Fixed-ratio and variable-ratio schedules of brief stimuli in second-order
      schedules of matching to sample.
AB  - Eight pigeons matched to sample under second-order schedules of food
      reinforcement. Under fixed-interval unit schedules, the first correct match to
      occur after a given period of time was followed by the presentation of a brief
      stimulus. The termination of the last fixed-interval unit schedule was followed
      by food according to second-order fixed-ratio and variable-ratio schedules. In
      Experiment 1, as the number of fixed-interval unit schedules increased, long
      pauses occurred under the second-order fixed-ratio schedules, but not under the
      variable-ratio schedules. The similarity of performance measures such as local
      rate and accuracy indicated that the differences engendered by these two types of
      schedule are in the duration of the periods of not-responding. In Experiment 2,
      the addition of a brief stimulus at the end of each unit schedule in chained
      schedules that had different discriminative stimuli present for the duration of
      each unit did not substantially affect the performance, and long pauses continued
      to occur. However, few long pauses occurred under schedules with brief stimulus
      presentations alone. The most inaccurate performances were engendered by chained
      schedules without brief stimuli.

PMID- 16811702
TI  - Choice of a terminating over a non-terminating signal in free-operant avoidance.
AB  - Rats chose between two signalled avoidance schedules. Under one schedule,
      responses in the presence of the signal terminated it and resulted in avoidance
      of shock; in the other, responses in the presence of the signal resulted in shock
      avoidance but signal termination was delayed for 10 sec. Pressing a second
      (changeover) lever produced change from one schedule to the other for 1 min. Once
      this 1-min period timed out, subjects could remain under the schedule in effect
      or could reinstate the other schedule for another 1-min period. All four subjects
      continuously changed over from the non-terminating to the terminating signal
      schedule. Changeover responding was not maintained when the termination
      contingency was removed. When changeover responding resulted in a change from a
      terminating to a non-terminating signal schedule, changeover responding did not
      occur.

PMID- 16811703
TI  - Behavioral contrast and inhibitory stimulus control as related to extended
      training.
AB  - Pigeons received discrimination training in which the presence of a white field
      was correlated with variable-interval reinforcement and the presence of a
      monochromatic field was correlated with extinction. Responses during the negative
      stimulus prolonged its duration. Five experimental groups each received a
      different number of discrimination sessions up to 70 sessions. The last session
      was followed by a wavelength generalization test. The control group was tested
      both before and after four discrimination sessions. Responding to the positive
      training stimulus was enhanced in all groups by the discrimination procedures.
      This enhancement tended to decrease over sessions in some animals but it never
      disappeared in others. Responding to the test stimuli preceding discrimination
      training was minimal around the negative stimulus and increased in either
      direction away from that wavelength. Responding to the test stimuli was not
      systematically related to the amount of discrimination training.

PMID- 16811704
TI  - The effect of overtraining on behavioral contrast and the peak-shift.
AB  - Following initial discrimination training between two wavelength stimuli and a
      subsequent generalization test to the wavelength dimension, Group 1 was
      "overtrained" for 105 days on the original discrimination. Group 2 was
      "overtrained" with the original positive stimulus and a new negative stimulus, a
      white line. Group 3 was "overtrained" with the original negative stimulus and a
      new positive stimulus, the white line. Each 15 days of extended training were
      followed by a wavelength generalization test similar to the first test. The
      results suggest that there is no consistent relationship between the response
      rate in positive stimulus immediately before the generalization test and whether
      or not a peak shift occurs during the test.

PMID- 16811705
TI  - Response-reinforcer dependence and independence in multiple and mixed schedules.
AB  - Albino rats were conditioned to lever press during two-component multiple and
      mixed schedules in which response-dependent and response-independent reinforcers
      occurred in the different components. Relative response rates in the components
      associated with response-dependent reinforcers were higher (a) when different
      visual and auditory stimuli were associated with the two components and (b) when
      mixed schedule components were long in duration. These results illustrate the
      contribution of the response-reinforcer relation to stimulus control and schedule
      control of behavior. They also suggest that under some conditions, reinforcers
      need not be consistently associated with a particular response to ensure that the
      response is maintained at a relatively high rate.

PMID- 16811706
TI  - Altering the proportion of components in a mixed fixed-ratio schedule.
AB  - Pigeons were trained under a schedule consisting of a number of fixed-ratio 100
      components followed by a single fixed-ratio 10 component. The proportion of fixed
      ratio 100 to fixed-ratio 10 components was varied according to several ascending
      and descending series within the range of 99:1 to 1:1. When this proportion was
      reduced to about 20:1 and below, the pause following each fixed-ratio 100
      gradually decreased in length. Primes, a burst of responses at the start of the
      fixed-ratio 100 component, increased in frequency, and then decreased when the
      proportion became extremely low. Also, when the relative frequency of fixed-ratio
      10 components was very high, primes were seldom observed in the first fixed-ratio
      100 component following a fixed-ratio 10 component, but were distributed evenly
      throughout the remaining fixed-ratio 100 components.

PMID- 16811707
TI  - A comparison of measures of responding under fixed-interval schedules.
AB  - Average response rate, post-reinforcement pause, elapsed time to the fourth
      response, average quarter-life, and running rate were examined to see how they
      reflected changes in fixed-interval performance. Rats were exposed to a mixed
      schedule of water presentation comprising fixed-interval schedules of two
      durations. Changes in responding were produced by varying the duration of the
      shorter component. The five measures were derived only from the longer schedule
      component. Post-reinforcement pause, elapsed time to the fourth response in the
      interval, and quarter-life all showed high, positive inter-correlations
      (0.78<r<0.99). Running rate and post-reinforcement pause were not as highly
      correlated. Quarter-life reliably reflected changes in fixed-interval performance
      but changes in the quarter-life value did not necessarily result from similar
      changes in fixed-interval response pattern. The two measures that adequately
      described changes in response patterning were post-reinforcement pause and
      running rate. These two measures also had the advantage of being simple both
      computationally and in terms of the instrumentation involved in their recording.

PMID- 16811708
TI  - The effect upon simple animal behavior of different frequencies of reinforcement,
      Part II: separate control of the reinforcement of different IRTs.
AB  - Rats' responding was stabilized for over 35 days on 4-min variable-interval
      reinforcement. Reinforcements per hour for 4-sec wide classes of interresponse
      times were then separately controlled by adjusting those for each class to the
      variable-interval values that had just prevailed. This produced little or no
      change in interresponse times, indicating that the new procedure was
      substantially equivalent to a variable-interval schedule. The variable-interval
      schedule produced a high and stable conditional probability of interresponse
      times in the 0- to 4-sec class, associated with a peak in reinforcements per hour
      for this class. Reducing the reinforcements per hour for this class while raising
      that for another class (by 3.3 reinforcements per hour) significantly reduced the
      conditional probability of 0- to 4-sec interresponse times. Restoring the 3.3
      reinforcements per hour to the 0- to 4-sec class significantly elevated the
      conditional probability of interresponse times in this class. Hence, it is
      concluded that the distribution of interresponse times produced by a subject
      during some variable-interval schedules is determined partly by the relative
      reinforcement of different interresponse times that the variable-interval
      schedule provided.Reprinted from Part II of the Final Report of Research under
      Contract DA-49-007-MD-408 with the Medical Research and Development Board, Office
      of the Surgeon General, Department of the Army, 31 December 1954. Edwin B.
      Newman, Responsible Investigator; Douglas Anger, Research Assistant and author of
      report. Experimental work done in the Psychological Laboratories of Harvard
      University.

PMID- 16811709
TI  - Time allocation and negative reinforcement.
AB  - Pigeons' standing on one or the other side of a chamber was reinforced with
      timeout from electric shock on two concurrent variable-interval schedules. For
      two pigeons, the ratio of time spent on the left to time spent on the right
      approximately matched the ratio of timeouts obtained on the left to timeouts
      obtained on the right. The data of two other birds deviated from this relation,
      although in opposite directions. Overall, the results suggest that reduction in
      rate of electric shock plays a role in behavioral allocation analogous to that
      played by rate of positive reinforcement. It appears possible to describe
      aversive control and positive control within the same conceptual framework-that
      provided by the matching relation.

PMID- 16811710
TI  - Controls for and constraints on auto-shaping.
AB  - Auto-shaping the pigeon's key-peck response was examined as a respondent
      conditioning procedure with the use of Rescorla's truly-random control procedure.
      In the first experiment, pigeons received presentations of brief light on the
      response key and brief presentations of food where the light and the food were
      independently presented. All birds failed to key peck after many light and food
      presentations, but explicit pairing of the light and food rapidly conditioned
      pecking to the light. Experiment 2 showed that even when an independent
      light/food presentation schedule was reduced to variable-time 30 sec, additional
      naive birds would not key peck and only one bird pecked when the schedules were
      variable-time 15 sec. A third experiment examined an explicit-unpairing control
      procedure, where the light and food were not only presented on independent
      schedules but were also separated by a minimum time, and found that auto-shaping
      did not occur. A fourth experiment investigated a number of control procedures
      and found them ineffective. A fifth experiment investigated the effects of a
      physical separation of the locus of the response key and the food dispenser, and
      a sixth experiment investigated using a tone in place of the light. It was
      concluded that pecking is generated by auto-shaping procedures only when an
      intermittently presented keylight is regularly paired with food.

PMID- 16811711
TI  - Suppression of random-ratio and acceleration of temporally spaced responding by
      the same prereward stimulus in monkeys.
AB  - A 1-min tone and light signal that preceded two free pellets of food suppressed
      the random-ratio responding of four rhesus monkeys, but accelerated the same
      subjects' responding on a differential-reinforcement-of-low-rate schedule in
      separate sessions. Both schedule-specific interactions occurred during the first
      presentations of the signal that previously had been paired with food outside the
      operant sessions. Thus, neither effect was adventitiously produced. In two
      subjects, both the direction and magnitude of the prereward change in
      differential-reinforcement-of-low-rate responding appeared related to baseline
      response rates: the more rapid the baseline responding, the less was the
      acceleration during the signal. Suppression and acceleration did not appear as
      dichotomous effects with separate parameters, but as related effects at least
      partly determined by the characteristics of the baseline operant performance.

PMID- 16811712
TI  - A test of the effectiveness of the differential-reinforcement-of-low-rate
      schedule.
AB  - Pigeons and rats were used in a yoked-control design that equated the
      reinforcement distributions of differential-reinforcement-of-low-rate and
      variable-interval schedules. Both a between-subjects design and a within-subjects
      design found response rate higher for the variable-interval schedule than for the
      differential-reinforcement-of-low-rate schedule, thus demonstrating the
      effectiveness of the differential-reinforcement-of-low-rate contingency. The
      interresponse-time distributions were unimodal for all subjects under the
      variable-interval schedule and bimodal for pigeons under the differential
      reinforcement-of-low-rate schedule. The interresponse-time distributions for rats
      under the differential-reinforcement-of-low-rate schedule were also bimodal in
      three of four cases but the height of the modes at the shorter interresponse
      times were small in both absolute value and in relation to the height of the
      modes at the shorter interresponse times of the pigeons' distributions.

PMID- 16811713
TI  - Preference for fixed-interval schedules: an alternative model.
AB  - Pigeons were trained under concurrent chain schedules in which the initial links
      were equal aperiodic schedules and the terminal links were fixed-interval
      schedules. Choice proportions in the initial links were measured in 26
      experimental conditions. The data showed the inadequacy of previous models of
      concurrent chain performance. A new model was suggested in which choice is a
      joint function of terminal-link times, overall reinforcement rates, and terminal
      link entries. This model accounted for 94% of the variance in the present data
      and for substantial percentages of the variance in previously reported data. The
      model simplifies to matching between response ratios and obtained reinforcement
      rate ratios for simple concurrent schedule performance.

PMID- 16811714
TI  - Application of a graded choice procedure to obtain errorless learning in
      children.
AB  - A simultaneous, two-choice color discrimination was carried out with three groups
      of four- to seven-year-old children. For Groups I and II, the opportunity to
      respond to the incorrect stimulus was controlled (graded) over three different
      conditions. First, only a red light (S+) and its retractable bar were presented
      (16 trials for Group I and 316 trials for Group II). Second, a green light (S-)
      was added with its correlated bar retracted for 14 trials. Third, 40 trials were
      given with both stimuli on and their correlated retractable bars extended. The
      opportunity to respond to S- was not graded for Group III children. They
      experienced only the third condition applied to Groups I and II. Responses to S+
      were reinforced for all three groups, while responses to S- were not. Children in
      the first two groups made from zero to three responses to S-, while the control
      children emitted 11 to 46 errors. The results demonstrate that fading in S- or
      presenting S- early in the training procedure are sufficient, but not necessary
      conditions for errorless learning.

PMID- 16811715
TI  - Observing responses in pigeons: effects of schedule component duration and
      schedule value.
AB  - Pigeons were exposed to a procedure under which five pecks on one response key
      (the observing key) changed the schedule on a second key (the food key) from a
      mixed schedule to a multiple schedule for 25 sec. In Experiment I, a random-ratio
      50 schedule alternated with extinction. The duration of the random-ratio 50
      schedule component was varied between 1.25 and 320 sec, and extinction was
      scheduled for a varying time, ranging from the duration of the random-ratio 50 to
      four times that value. Each set of values was scheduled for a block of sessions.
      Before observing-key pecks were allowed at each set of parameter values, the
      pigeons were exposed to a condition where the mixed and multiple schedule
      alternated every 10 min, and observing-key pecks were not permitted. Rates of
      pecking on the observing key were high for all values of random-ratio component
      durations except 1.25 sec. Experiment II was conducted with the random-ratio
      component duration equal to 40 sec, and the random-ratio schedule was varied from
      random-ratio 50 to 100, 200, and 400. Observing-key pecking rates were high for
      all values of the random-ratio schedule except random-ratio 400. In both
      experiments, observing response rates were relatively little affected, suggesting
      that neither schedule component duration nor schedule value is a strong
      determinant of observing responses.

PMID- 16811716
TI  - Effects of stimulus duration on observing behavior maintained by differential
      reinforcement magnitude.
AB  - Pigeons made observing responses for stimuli signalling the availability of
      either 10-sec or 2-sec access to grain on fixed-interval 1-min schedules. If
      observing responses did not occur, food-producing responses occurred to a
      stimulus common to both reinforcement magnitudes. When the stimuli remained on
      for the duration of the components and signalled differential reinforcement
      magnitudes, observing responses were maintained; however, when the stimuli
      remained on for 10 sec, observing responses decreased markedly. In addition, it
      was shown that the occasional presentation of the stimulus signalling 10-sec
      access to grain was necessary for the maintenance of observing behavior. A
      control condition demonstrated that when all the available stimuli signalled 6
      sec access to grain, observing responses declined. Taken together, the results
      demonstrated that the occasional presentation of the stimulus that remained on
      for the duration of the component and signalled the larger reinforcement
      magnitude was necessary for the maintenance of observing behavior.

PMID- 16811717
TI  - Second-order schedules: a comparison of chained, brief-stimulus, and tandem
      procedures.
AB  - Pigeons were exposed to seven types of two-component schedules, each component a
      2-min fixed-interval schedule. Food presentation occurred at the completion of
      the second component under all conditions. The seven types of schedules were: (1)
      a chained schedule in which completion of the first component produced the
      discriminative stimulus associated with the second component; (2) a chained
      schedule to which was added the brief presentation of a food-paired stimulus at
      the completion of the first component; (3) a chained schedule to which was added
      the brief presentation of a stimulus not paired with food at the completion of
      the first component; (4) a multiple schedule in which food presentation occurred
      at the completion of both components; (5) a tandem schedule in which completion
      of the first component initiated the second component, with no changes in
      exteroceptive stimuli; (6) a food-paired brief-stimulus schedule in which the
      brief presentation of a food-paired stimulus was made at the completion of the
      first component and no other changes in stimuli occurred; and (7) a brief
      stimulus schedule in which the brief presentation of a stimulus not paired with
      food was made at the completion of the first component and no other changes in
      stimuli occurred. Positively accelerated patterns of responding developed in the
      first component under three conditions: (1) the chained schedule with the added
      food-paired brief stimulus; (2) the multiple schedule; and (3) the food-paired
      brief-stimulus schedule. Response rates were low in the first component, with few
      instances of positively accelerated patterns, under two conditions: (1) the
      chained schedule; and (2) the chained schedule with the added nonpaired brief
      stimulus. The results suggest that a briefly presented food-paired stimulus may
      function as a more effective conditioned reinforcer than does the presentation of
      a discriminative stimulus.

PMID- 16811718
TI  - Reinforcer effectiveness as a function of reinforcer rate and magnitude: a
      comparison of concurrent performances.
AB  - Pigeons' pecks on each of two concurrently available response keys were
      reinforced under a variable-interval schedule that sometimes allotted food-pellet
      deliveries to one key and sometimes to the other. The keys differed in the number
      of reinforcements assigned to each and in the number of pellets delivered during
      each reinforcement. When the total quantity of food associated with each key
      during a session was constant, the proportion of responses to a key depended on
      the particular combinations of reinforcer rate and reinforcer magnitude scheduled
      on each key. A given quantity of food generated more responding on a key when it
      was delivered frequently in small amounts than when it was delivered infrequently
      in large amounts.

PMID- 16811719
TI  - Stimulus control in a two-choice discrimination procedure.
AB  - The relation between performance during discriminative training and subsequently
      obtained measures of stimulus control was investigated. Pigeons served as
      experimental subjects. In the discriminative training phase, a single peck on the
      center key, transilluminated by a bright or dim white light, resulted in the
      onset of the side keys, one red and one green. If the center key was brightly
      lighted, a response on the red side key was correct. A response on the green side
      key was correct if the center key was dimly lighted. Correct responses were
      reinforced on independently arranged variable-interval schedules. Following
      discriminative training, tests of stimulus control were administered during which
      white light of 11 intensities was projected on the center key and responses on
      the red and green side keys recorded. The proportion of correct responses in the
      presence of a bright or dim center-key stimulus decreased with decreases in the
      frequency of reinforcement of correct red or correct green responses,
      respectively. The slopes of the stimulus control gradients were related to the
      extent of response bias during training. The greater the bias to respond on the
      green key, the flatter the gradient showing the proportion of green-key responses
      to each stimulus and the steeper the corresponding gradient of red-key responses.

PMID- 16811720
TI  - Behavioral interactions and stimulus control during conditional discriminations.
AB  - Two pigeons were exposed to factorial combinations of two values of line tilt and
      two frequencies of houselight flashes. During each of four baseline stages, key
      pecking in the presence of all four combinations was reinforced according to a
      variable-interval schedule. The baseline phases were followed by four different
      conditional discrimination training procedures in which reinforcement
      availability for pecking in the presence of the line tilts depended upon the
      houselight frequency. The subjects acquired each conditional discrimination.
      Behavioral contrast occurred during the acquisition and abolition of the
      discriminations. Generalization tests, given after each conditional
      discrimination, revealed that both the line tilt and houselight frequency
      dimensions controlled pecking only after conditional discriminations in which
      reinforcement availability depended upon the value of both dimensions.

PMID- 16811721
TI  - A local-rate-of-response and interresponse-time analysis of behavioral contrast.
AB  - Three pigeons were exposed to a two-component multiple schedule in which a
      variable-interval 3-min schedule was always in effect in one component. The
      schedule in the other component was either variable-interval 3-min or extinction
      in alternate blocks of sessions. When the schedule was changed from multiple
      variable-interval 3-min variable-interval 3-min to multiple variable-interval 3
      min extinction in the second and fourth phases of the experiment, overall
      response rates in the unchanged variable-interval 3-min component increased in
      two pigeons. Response rate declined when the schedule was changed to multiple
      variable-interval 3-min variable-interval 3-min again. Correlated with increases
      in overall response rate in the unchanged component were increases in local
      response rates at the beginning of the unchanged component and immediately after
      food presentation. Local rates 40 sec after food presentation did not increase
      greatly in the presence of the multiple variable-interval 3-min extinction
      schedule. An interresponse time analysis of three local rate samples showed small
      increases in the relative frequency of short-duration interresponse times at the
      beginning of the unchanged component and immediately after food presentation.
      Neither the postreinforcement pause nor the latency to the first response in the
      unchanged component changed systematically.

PMID- 16811722
TI  - Failure to obtain positive contrast when pigeons press a bar.
AB  - In Experiment 1, two groups of pigeons were exposed to multiple variable-interval
      1-min variable-interval 1-min schedules of reinforcement. The required response
      was a key peck for one group, and a foot press of a bar for the other. When the
      procedure was shifted to multiple variable-interval 1-min extinction, positive
      contrast occurred with pigeons that key pecked, whereas negative induction
      occurred with those that bar pressed. Moreover, the absence of contrast could not
      be ascribed to the lack of inhibition, since negative generalization gradients
      after bar press training were U-shaped in Experiment 2. The results are discussed
      in terms of possible relationships between positive contrast and the phenomenon
      of autoshaping.

PMID- 16811723
TI  - Interactions in multiple schedules with different responses in each of the
      components.
AB  - Pigeons were exposed to multiple schedules in which a key was lit in one
      component and a bar was present in the other. Ten subjects were trained to peck
      the key and to press the bar with their feet, and four subjects were trained to
      peck both the bar and the key. After a period of exposure to variable-interval
      reinforcement in both components, subjects were exposed to extinction in one
      component. Only one of the 10 pigeons in the key-peck:bar-press condition showed
      an increase in rate in the other component, while seven of them showed a
      decrease. In the key-peck:bar-peck condition, three of the four subjects showed
      positive contrast. The data suggest that a condition for contrast to occur is
      that topographically similar behaviors be required in both components of the
      multiple schedule.

PMID- 16811724
TI  - Choice between response rates.
AB  - Three pigeons were required to peck a single key at a higher and a lower rate,
      corresponding to two classes of shorter and longer concurrently reinforced
      interresponse times. Food reinforcers arranged by a single variable-interval
      schedule were randomly allocated to the two reinforced interresponse times. The
      absolute durations of reinforced interresponse times were varied while the total
      reinforcements per hour was held constant and the relative duration, i.e., the
      relative reciprocal, of the shorter reinforcer class was held constant at 0.70.
      Preference for the higher rate of responding, as measured by the relative
      frequency of responses terminating interresponse times in the shorter reinforced
      class, depended on the absolute reinforced response rates. Preference for the
      higher reinforced rate increased from a level of near-indifference (0.50) at high
      reinforced response rates, through the matching level (0.70) at intermediate
      reinforced response rates, to a virtually exclusive preference (>0.90) at low
      reinforced response rates. These results resemble corresponding preference
      functions obtained with two-key concurrent-chains schedules and thereby provide
      another sense in which it may be said that interresponse-time distributions from
      interval schedules estimate preference functions for the component response rates
      corresponding to different classes of reinforced interresponse times.

PMID- 16811725
TI  - "Automaintenance": the role of reinforcement.
AB  - A key was illuminated on the average of every 30 sec for a duration of 6 sec and
      this was followed by food presentations. When key pecks in the presence of the
      light produced immediate access to grain (autoshaping procedure) pigeons were
      likely to peck. When pecks terminated the keylight but prevented access to grain
      (automaintenance procedure) pigeons were much less likely to peck. Seven of 12
      pigeons failed to develop responding during the automaintenance procedure. Four
      of the five pigeons that responded during the automaintenance procedure were
      exposed to a procedure in which responses could not immediately terminate the
      light. Three of the four ceased to respond during optimal automaintenance
      conditions, suggesting that the response-dependent offset of the keylight had
      been reinforcing their pecking. Responding during the automaintenance procedure
      was eliminated for a fifth pigeon by eliminating the contiguity of light-offset
      and food-onset on those trials in which the pigeon did not peck. These results
      suggest that: (1) automaintenance (unlike autoshaping) is not an effective
      procedure for reliably generating responding; (2) responding that does occur
      during the automaintenance procedure is reinforced by the response-dependent
      offset of the keylight.

PMID- 16811726
TI  - The effects of reinforcement upon the prepecking behaviors of pigeons in the
      autoshaping experiment.
AB  - The autoshaping procedure confounds the effects of pairing a keylight and food
      with the effect of adventitious food reinforcement of responses that typically
      occur before the pecking response. In Experiment I, acquisition of the
      orientation to the key, the approach toward the key, and the peck at the key were
      systematically monitored. Orientations to the key and approaches toward the key
      frequently occurred in contiguity with food presentation before peck acquisition.
      In Experiment II, a negative contingency procedure was used to assess the
      sensitivity of the approach toward the key to its consequences. When the approach
      toward the key resulted in nonreinforcement, the probability of occurrence of
      that response decreased to zero despite repeated light-food pairings. In
      Experiment III, peck probability was shown to be determined during the approach
      toward the key by the presence of stimuli that had previously been either paired
      or nonpaired with food. In Experiment IV, it was shown that the effects of the
      stimulus present during the approach toward the key were not due solely to the
      effects of pairing that stimulus with food. Autoshaped key pecking appears to be
      determined by the interacting effects of stimulus-reinforcer and response
      reinforcer variables upon orientations to, approaches toward, and pecks at the
      lighted key.

PMID- 16811727
TI  - The role of autopecking in behavioral contrast.
AB  - Four groups of four pigeons each were studied on two different multiple
      schedules. The cues correlated with the schedule components were localized on the
      response key for two groups and were not localized for the others. Two groups
      worked on multiple schedules with variable interval 15-sec in both components,
      and variable interval 15-sec in one component and extinction in the other. The
      other two groups had identical procedures except that food was presented on a
      response-independent variable-time schedule. Variable-interval birds with
      localized stimuli showed marked behavioral contrast; variable-interval birds with
      non-localized stimuli showed no behavioral contrast. Variable-time birds with key
      light stimuli acquired high rates of autopecking, which changed as treatment
      changed in a manner that paralleled rate changes, resulting in behavioral
      contrast for variable-interval birds. Variable-time birds with non-localized
      stimuli key pecked only at a low rate. The findings indicate that behavioral
      contrast in pigeons may result from the autopecking that is obtained with
      stimulus-contingent food presentation.

PMID- 16811728
TI  - Formal properties of the matching law.
AB  - The matching law implies that any form of behavior approaches an asymptotic
      frequency as its reinforcement approaches 100 per cent of the total reinforcement
      being obtained at a given time. This asymptote is formally independent of the
      kind or quantity of drive or reinforcement associated with the response in
      question or with any competing response.

PMID- 16811729
TI  - Handwriting as an operant.
AB  - An apparatus was designed to monitor handwriting behavior. Two subjects were
      studied under various schedules of monetary reinforcement for handwriting. The
      different schedules engendered and maintained distinctive response patterns but
      the rates of sustained responding did not vary across schedules. The development
      of fixed-interval performance following continuous reinforcement resembled the
      same transition in lower animals. In one subject, availability of reading
      material interacted with the schedule to determine response pattern. It was
      suggested that handwriting may be a more appropriate response for the
      experimental analysis of human behavior than the more frequently used button
      pushing or lever-pulling responses.

PMID- 16811730
TI  - Integrated circuit power supplies.

PMID- 16811731
TI  - Fixed-ratio and fixed-interval schedule control of matching-to-sample errors by
      children.
AB  - Nine children, ages 4 through 7 yr, matched-to-sample on fixed-ratio, fixed
      interval, variable-ratio, and variable-interval schedules of reinforcement.
      Simultaneous, zero-delay, and 2-sec delay matching were employed. Distributions
      of errors, in which the greatest number of errors occurred at the ordinal
      position immediately after reinforcement with fewer errors occurring at
      subsequent positions in the ratio, were produced by six of six children on fixed
      ratio schedules for zero-delay and both of two children for 2-sec delay matching.
      Only two children of seven produced similar error distributions on simultaneous
      matching for fixed-ratio reinforcement. Variable-ratio schedules produced
      slightly lower accuracy for most subjects and no systematic error patterns for
      any subject. Error distributions occurred for all of the five children who
      experienced fixed-interval schedules for zero-delay matching. Peak error
      production occurred in the second fourth of the interval. Similar patterns were
      not produced on variable-interval schedules of equal reinforcement density.
      Schedule control of complex discriminated operants in children resembles control
      over similar responses of nonhuman animals.

PMID- 16811732
TI  - Timeout as a reinforcer for errors in a serial position task.
AB  - After learning to press keys in a predetermined serial position sequence, with
      timeouts scheduled as a consequence of errors, monkeys developed stereotyped
      errors. As soon as a new trial started, the animals would make an error. On trial
      after trial, they pressed the same incorrect key at the first member of the
      sequence, even though they had previously learned the sequence. First-member
      errors occurred even when sequences of fully bright keys marking correct choices
      were presented. When timeout was eliminated as a consequence of one first-member
      error, subjects switched to an error that did produce the timeout. When all first
      member errors failed to produce timeout the monkeys ceased responding. Both
      prefeeding and reduction in reinforcement density resulted in stereotyped errors
      occurring earlier in the session.

PMID- 16811734
TI  - Conditioned suppression, punishment, and aversion.
AB  - Three experiments were conducted to assess the aversive properties of a visual
      stimulus in the presence of which one group of birds received response-contingent
      shock (discriminated punishment) while a yoked group of birds received non
      contingent shocks (conditioned suppression). In Experiment 1, presentation of the
      visual stimulus contingent on key pecking reduced the response rate (conditioned
      punishment effect) for birds under the conditioned suppression procedure but did
      not reduce the response rate of birds under the discriminative punishment
      procedure. Non-contingent shocks also produced greater suppression of responding
      maintained by positive reinforcement in the presence of a visual stimulus than
      did response-contingent shocks. In Experiment 2, a greater shock intensity (2 mA)
      was used. All the differences between the two groups found in Experiment 1 were
      also found in Experiment 2. Experiment 3 demonstrated that response-contingent
      shock did not result in a conditioned punishment effect even when positive
      reinforcers were unavailable during the discriminative punishment schedule. The
      exteroceptive stimulus that was paired with shock in the conditioned suppression
      procedure acquired the ability to punish behavior. The exteroceptive stimulus in
      the discriminative punishment schedule did not acquire this ability.

PMID- 16811733
TI  - Punishment of observing by the negative discriminative stimulus.
AB  - To determine the effect of a negative discriminative stimulus on the response
      producing it, two pigeons were each studied in a three-key conditioning chamber.
      During alternating periods of unpredictable duration, pecking the center (food)
      key either was reinforced with grain on a variable-interval schedule or was never
      reinforced. On equal but independent variable-interval schedules, pecking either
      of the side (observing) keys changed the color of all keys for 30 sec from yellow
      to either green or red. When the schedule on the center key was variable-interval
      reinforcement, the color was green (positive discriminative stimulus); when no
      reinforcements were scheduled, the color was red (negative discriminative
      stimulus). Since pecking the side keys did not affect grain deliveries, changes
      in the rate of pecking could not be ascribed to changes in the frequency of
      primary reinforcement. In subsequent sessions, red was withheld as one of the
      possible consequences of pecking a given side key. When red was omitted, the rate
      on that key increased, and when red was restored, the rate decreased. It was
      concluded that red illumination of the keys, the negative discriminative
      stimulus, had a suppressive effect on the response that produced it.

PMID- 16811735
TI  - Generalization of free-operant avoidance behavior in pigeons.
AB  - Three groups of four pigeons, trained to press a treadle on a free-operant
      avoidance schedule, were given auditory discrimination training. Alternating 2
      min components of avoidance and no shock were paired with either a tone or white
      noise. The pigeons were subsequently given two types of generalization tests,
      with and without avoidable shocks scheduled. Two of the groups, trained
      interdimensionally, produced excitatory and inhibitory generalization gradients
      along the tone frequency dimension. A predicted post-discrimination gradient was
      computed from the algebraic summation of these gradients of excitation and
      inhibition. The predicted gradient was compared with the actual post
      discrimination gradient obtained from the third group of pigeons that had been
      given intradimensional discrimination training on the tone frequency dimension.
      The predicted postdiscrimination gradient agreed in shape with the empirical
      postdiscrimination gradient. The results in general support Spence's (1937)
      gradient interaction theory.

PMID- 16811736
TI  - Preference for and effects of variable-as opposed to fixed-reinforcer duration.
AB  - Pigeons were trained on multiple schedules in which a fixed number of pecks
      produced either a fixed or a variable period of access to food, the average
      variable-duration reinforcement equalling the fixed. Pecking rates were generally
      higher during the variable-duration component. Subsequent performance on
      concurrent schedules revealed an initial preference for variable-duration
      reinforcement for all subjects; for most subjects, this preference was sustained.
      For one subject, the average variable duration was gradually reduced to half the
      fixed duration: continued preference for the variable component resulted in a
      loss of up to 30% of available reinforcement time. A return to multiple schedules
      with unequal pay-off shifted the preference to the greater fixed duration, and
      this preference was maintained even when the variable duration was again raised
      to equal the fixed duration. For the remaining subjects, the initial variable
      duration preference on concurrent schedules was gradually replaced by a side
      preference. When the range of variable durations was varied, keeping the average
      variable duration equal to the fixed, the occasional longer reinforcers sustained
      a preference for variable-reinforcer durations for three of the four subjects.

PMID- 16811737
TI  - Concurrent performances: stimulus-control gradients during schedules of signalled
      and unsignalled concurrent reinforcement.
AB  - On one key, pigeons' pecks were reinforced according to a variable-interval
      schedule in the presence of vertical lines, and were not reinforced in the
      presence of oblique lines. On a second key, pecks were reinforced according to a
      variable-interval schedule in the presence of blue, according to a signalled
      variable-interval schedule in the presence of red, and were not reinforced in the
      presence of white. Subsequently, during extinction, stimulus-control gradients
      were obtained by presenting eight different line orientations on the first key
      concurrent with each of the three colors on the second key. On the first key,
      line-orientation gradients tended to be lower, narrower, and less shifted in peak
      or area when the second-key stimulus was blue or red, the stimuli respectively
      correlated with unsignalled and signalled reinforcement, than when it was white,
      the stimulus correlated with extinction. Thus, the effect on first-key line
      orientation gradients depended on second-key stimuli correlated with concurrent
      reinforcement, whether or not these stimuli were also correlated with concurrent
      responding. As a function of first-key line orientation, an inverted gradient was
      obtained on the second key during blue; during both red and white, rates of
      pecking on the second key were near zero.

PMID- 16811738
TI  - Transfer of matching-to-sample in pigeons.
AB  - In Experiment I, pigeons were first trained on simultaneous matching-to-sample
      with either color stimuli or form stimuli, and then shifted to stimuli on the
      other dimension. Matching performance in the first session with stimuli on a
      given dimension was not affected by prior matching training with stimuli on the
      other dimension. However, in the first six color-matching sessions pooled, birds
      with prior form-matching training performed significantly better than birds
      without any prior matching training. In Experiment II, birds with experience
      matching both colors and forms in separate sessions were tested with novel
      stimulus configurations involving either novel stimuli or novel combinations of
      familiar colors and forms. Matching performance was not affected by novel
      stimulus configurations, except that performance dropped to a chance level or
      below when the standard stimulus was novel. In Experiments II, III, and IV, three
      of four tests did not show any effect of prior reinforcement of pecks at a novel
      stimulus, presented alone, on subsequent matching of that stimulus. The results
      were interpreted as indicating that matching performance in pigeons depends on
      the learning of stimulus-response chains involving the specific stimuli employed
      during training. An incidental observation in Experiments I and II was that there
      were typically more excess pecks at the standard stimulus during form-matching
      sessions than during color-matching sessions, which may be related to the fact
      that form matching is more difficult than color matching.

PMID- 16811739
TI  - Effects of response rate, reinforcement frequency, and the duration of a stimulus
      preceding response-independent food.
AB  - Food-reinforced key pecking in the pigeon was maintained under a four-component
      multiple schedule. In two components, responding was maintained at high rates
      under a random-ratio schedule. In the other two components, responding was
      maintained at low rates under a schedule that specified a minimum interresponse
      time. For both high and low response rates, one of the schedule components was
      associated with a high reinforcement frequency and the other components with a
      lower reinforcement frequency. During performance under these schedules, a
      stimulus terminated by access to response-independent food was periodically
      presented. The duration of this pre-food stimulus was 5, 30, 60, or 120 sec.
      Changes in rate of key pecking during the pre-food stimulus were systematically
      related to baseline response rate and the duration of the stimulus. Both high and
      low response rates were increased during the 5-sec stimulus. At longer stimulus
      durations, low response rates were unaffected and high response rates were
      decreased during the stimulus. For two of three pigeons, high response rates
      maintained under a lower frequency of reinforcement tended to be decreased more
      than high response rates maintained under a higher reinforcement frequency. In
      general, the magnitude of decrease in high response rates was inversely related
      to the duration of the pre-food stimulus.

PMID- 16811740
TI  - The law of effect and avoidance: a quantitative relationship between response
      rate and shock-frequency reduction.
AB  - Two experiments were conducted to investigate the quantitative relationship
      between response rate and reinforcement frequency in single and multiple variable
      interval avoidance schedules. Responses cancelled delivery of shocks that were
      scheduled by variable-interval schedules. When shock-frequency reduction was
      taken as the measure of reinforcement, the relationship between response rate and
      reinforcement frequency on single variable-interval avoidance schedules was
      accurately described by Herrnstein's (1970) equation for responding on single
      variable-interval schedules of positive reinforcement. On multiple variable
      interval avoidance schedules with brief components, asymptotic relative response
      rate matched relative shock-frequency reduction. The results suggest that many
      interactions between response rates and shock-frequency reduction in avoidance
      can be understood within the framework of the generalized matching relation, as
      applied by Herrnstein (1970) to positive reinforcement.

PMID- 16811741
TI  - On the form of the relation between response rates in a multiple schedule.
AB  - Three pigeons received training on multiple variable-interval schedules with
      brief alternating components, concurrently with a fixed-interval schedule of food
      reinforcement on a second key. Fixed-interval performance exhibited typical
      increases in rate within the interval, and was independent of multiple-schedule
      responding. Responding on the multiple-schedule key decreased as a function of
      proximity to reinforcement on the fixed-interval key. The overall relative rate
      of responding in one component of the multiple schedule roughly matched the
      overall relative rate of reinforcement. Within the fixed interval, response rate
      during one multiple-schedule component was a monotonic, negatively accelerated
      function of response rate during the other component. To a first approximation,
      the data were described by a power function, where the exponent depended on the
      relative rate of reinforcement obtained in the two components. The relative rate
      of responding in one component of the multiple schedule increased as a function
      of proximity to fixed-interval reinforcement, and often exceeded the overall
      obtained relative rate of reinforcement. The form of the function relating
      response rates is discussed in relation to findings on rate-dependent effects of
      drugs, chaining, and the relation between response rate and reinforcement rate in
      single-schedule conditions.

PMID- 16811742
TI  - The role of elicited responding in behavioral contrast.
AB  - An attempt was made to separate operant and elicited pecks occurring in multiple
      schedules of food reinforcement by moving the component stimuli to a second key,
      upon which pecks had no effect. The operant key stimulus was constant, regardless
      of the reinforcement schedule in effect. Experiments included two- and three
      component multiple schedules and a comparison of the single-key and the two-key
      procedures. In general, conditions that typically produce positive contrast in
      single-key procedures reduced responding to the constant-stimulus key (induction)
      and increased responding to the component-stimulus key (contrast) in the two-key
      procedure. The results were interpreted as supporting the contention that two
      response classes, operant and elicited, are present in standard multiple
      schedules. In addition, elicited responses were strongly implicated in contrast
      phenomena.

PMID- 16811743
TI  - The relationship between observing behavior and food-key response rates under
      mixed and multiple schedules of reinforcement.
AB  - Pigeons were trained under an observing response procedure in which pecks on one
      key (food key) were reinforced under a mixed fixed-interval 30-sec extinction
      schedule. A response on a second (observing) key replaced the mixed-schedule
      stimulus with either of two multiple-schedule stimuli (red and green keylights)
      for 5 sec. Observing response rates were positively correlated with food-key
      response rates in the presence of multiple-schedule stimuli and inversely related
      to food-key response rates in the presence of mixed-schedule stimuli. These
      results suggest that observing response output is controlled not only by the
      stimuli produced by observing responses but also by the stimuli in the presence
      of which observing responses occur. The possibility that observing responses
      alter the probability of reinforcement is advanced.

PMID- 16811744
TI  - Effects of response-produced stimuli upon conditional discrimination performance.
AB  - In zero-delay matching procedures the performance of three groups of pigeons was
      examined when exteroceptive stimuli, response-produced stimuli associated with
      the completion of either of two fixed ratios, or a compound of exteroceptive and
      response-produced stimuli were available as samples. Exteroceptive samples were
      found to control a higher level of matching accuracy than response-produced
      samples, while compound samples controlled a higher level of accuracy than did
      exteroceptive samples alone. When all subjects were placed on a transfer
      procedure, during which the previously used red and green samples were replaced
      by horizontal and vertical lines, the availability of sample-specific fixed
      ratios facilitated acquisition of the task.

PMID- 16811745
TI  - Choice behavior on discrete trials: a demonstration of the occurrence of a
      response strategy.
AB  - Three pairs of pigeons were trained to peck at two keys presented simultaneoulsy
      in discrete trials with intertrial intervals of 1, 22, or 120 sec. Left-key
      responses incremented the probability of reinforcement for the first right-key
      response and, conversely, right-key responses incremented the probability of
      reinforcement for the first left-key response. In terms of relative response
      rates, it was found that all birds' choices were described by a momentary
      maximizing strategy, but this fact was not reflected in the detailed sequential
      statistics for birds with the longer (22 or 120 sec) intertrial intervals. It was
      hypothesized that choice behavior, in general, may be accurately described by a
      momentary maximizing sequence, but that prior failures to demonstrate this were
      due to "errors" in executing the momentary maximizing sequence. These
      misappropriated responses, which are hypothesized to be randomly distributed
      among the responses defining the momentary maximizing sequence, caused successive
      choices to appear to be statistically independent when, in fact, they were not.

PMID- 16811746
TI  - A functional analysis of chained fixed-interval schedule performance.
AB  - Three pigeons were trained on two-link chained fixed-interval fixed-interval
      schedules. Numbers of responses, time spent responding, and the total time spent
      in each component were measured. The data were analyzed according to the matching
      law for multiple and concurrent schedules. In most conditions, the ratio of
      response rates in the two links was a constant proportion of the ratio that would
      be predicted in a multiple schedule with the same components. Data on pauses
      during the interval schedules showed that, in most conditions, the pause duration
      was a linear function of the interval length, and greater in the initial link
      than in the terminal link. The experiment thus demonstrated a quantitative
      functional analysis of performance on a chained schedule.

PMID- 16811747
TI  - Preference for fixed-interval schedules: effects of initial-link length.
AB  - Six homing pigeons were trained on a variety of concurrent-chains schedules in
      which the initial links were equal variable-interval schedules and the terminal
      links were fixed-interval schedules. Both terminal-link and initial-link
      schedules were systematically varied. The results showed that preference for a
      particular terminal-link schedule combination was greater, the shorter the
      initial-link schedules. The data closely matched predictions from the model of
      choice suggested by Davison and Temple (1973), but did not match predictions from
      two other models. An alternative method for analyzing concurrent-chains
      performance by assuming that the schedule consists of both chained schedules and
      successive, discriminated components that comprise multiple schedules, was
      suggested.

PMID- 16811748
TI  - Latency and frequency of responding under discrete-trial fixed-interval schedules
      of reinforcement.
AB  - Pigeons' key pecking was studied under a number of discrete-trial fixed-interval
      schedules of food reinforcement. Discrete trials were presented by briefly
      illuminating the keylight repetitively throughout the interreinforcement
      interval. A response latency counterpart to the fixed-interval scallop was found,
      latency showing a gradual, negatively accelerated decrease across the interval.
      This latency pattern was largely invariant across changes in fixed-interval
      length, number of trials per interval, and maximum trial duration. Frequency of
      responding during early trials in the intervals varied, however, with different
      schedule parameters, being directly related to fixed-interval length, inversely
      related to number of trials, and complexly affected by conjoint variations of
      fixed-interval length and number of trials. Response latency thus was found to be
      simply related to elapsed time during the interval while response frequency was
      complexly determined by other factors as well.

PMID- 16811749
TI  - Autoshaping and automaintenance of a key-press response in squirrel monkeys.
AB  - Following exposure for a minimum of 500 to 600 trials, three of four naive
      squirrel monkeys eventually pressed a response key, illumination of which always
      preceded delivery of a food pellet. Three other naive monkeys did not press the
      key when the pellets were delivered randomly with respect to key illumination.
      Despite some similarities to autoshaping using pigeons, the data indicate many
      points of difference when squirrel monkeys are used as subjects. Although key
      food pairings were shown to be important in the acquisition of the key-press
      response, they were ineffective in maintaining the response when either a
      negative response-reinforcer dependency was introduced, or when there was no
      scheduled response-reinforcer dependency (fixed trial). Not all demonstrations of
      autoshaping can be considered to be under the control of those processes that are
      primarily responsible for the phenomena obtained in pigeons.

PMID- 16811750
TI  - Signal detection methods for measurement of utility in animals.
AB  - Analytic methods of signal detection theory were employed to assess the utility
      of reinforcers. Four pigeons were trained to detect the presence or absence of a
      stimulus by pecking one of two side keys in a trial-by-trial choice paradigm. The
      relative rate of positive reinforcement for correct choices was varied to offset
      the biasing effects of electric shock for incorrect right side-key choices. The
      effects of relative rate of reinforcement on bias were similar at all shock
      intensities even though the subjects' sensitivity changed during the course of
      the experiment. The relative rate of reinforcement required to produce equal bias
      was calculated and plotted against shock intensity to generate utility functions.
      The relative rate of reinforcement necessary to offset the bias induced by shock
      was an increasing function of shock intensity.

PMID- 16811751
TI  - Modifying the Gerbrands cumulative recorder to produce histograms.

PMID- 16811753
TI  - Effects of reinforcement rate and reinforcer magnitude on choice behavior of
      humans.
AB  - Two experiments with human subjects investigated the effects of rate of
      reinforcement and reinforcer magnitude upon choice. In Experiment 1, each of five
      subjects responded on four concurrent variable-interval schedules. In contrast to
      previous studies using non-human organisms, relative response rate did not
      closely match relative rate of reinforcement. Discrepancies ranged from 0.03 to
      0.43 (mean equal to 0.19). Similar discrepancies were found between relative
      amount of time spent responding on each schedule and the corresponding relative
      rates of reinforcement. In Experiment 2, in which reinforcer magnitude was varied
      for each of five subjects, similar discrepancies ranging from 0.05 to 0.50 (mean
      equal to 0.21), were found between relative response rate and relative proportion
      of reinforcers received. In both experiments, changeover rates were lower on the
      long-interval concurrent schedules than on the short-interval ones. The results
      suggest that simple application of previous generalizations regarding the effects
      of reinforcement rate and reinforcer magnitude on choice for variable-interval
      schedules does not accurately describe human behavior in a simple laboratory
      situation.

PMID- 16811752
TI  - Response strength in multiple schedules.
AB  - In several different experiments, pigeons were trained with one schedule or
      condition of food reinforcement for pecking in the presence of one key color, and
      a different schedule or condition in the presence of a second key color. After
      responding in both of these multiple schedule components stabilized, response
      independent food was presented during dark-key periods between components, and
      the rates of pecking in both schedule components decreased. The decrease in
      responding relative to baseline depended on the frequency, magnitude, delay, or
      response-rate contingencies of reinforcement prevailing in that component. When
      reinforcement was terminated, decreases in responding relative to baseline rates
      were ordered in the same way as with response-independent food. The relations
      between component response rates were power functions. Internal consistencies in
      the data, in conjunction with parallel findings in the literature, suggest that
      the concept of response strength summarizes the effects of diverse procedures,
      where response strength is identified with relative resistance to change. The
      exponent of the power function relating response rates may provide the basis for
      scaling response strength.

PMID- 16811754
TI  - Stimulus control of responding during a fixed-interval reinforcement schedule.
AB  - During training sessions, pecks by pigeons on a response key illuminated by a
      vertical line of white light resulted in reinforcement and an ensuing blackout
      according to a fixed-interval schedule. Training sessions were followed by
      dimensional stimulus control test sessions during which the orientation of the
      line present throughout the fixed interval was varied. Inverted U-shaped
      (excitatory) gradients of responding, with maximum responding occurring in the
      presence of the vertical line, were observed during the terminal part of the
      fixed interval. U-shaped (inhibitory) gradients of responding, with minimum
      responding occurring in the presence of the vertical line, were observed during
      the early part of the fixed interval when the preceding interval had terminated
      with reinforcement and blackout but not when the preceding interval had
      terminated with blackout only. These results suggest that the dimensional control
      by the stimulus present throughout the fixed interval is of a conditional
      variety. Whether the fixed-interval stimulus exerts inhibitory or excitatory
      dimensional control depends upon the presence and absence, respectively, of
      stimuli associated with reinforcement.

PMID- 16811755
TI  - Schedules of response-independent conditioned reinforcement.
AB  - Rates and patterns of responding of pigeons under response-independent and
      response-dependent schedules of brief-stimulus presentation were compared by
      superimposing 3-min brief-stimulus schedules on a 15-min fixed-interval schedule
      of food presentation. The brief-stimulus schedules were fixed time, fixed
      interval, variable time, and variable interval. When the brief stimulus was
      paired with food presentation, its effects depended upon the schedule and ongoing
      rates. Fixed- and variable-interval brief-stimulus schedules enhanced the low
      rates normally occurring early in the 15-min interval, whereas fixed- and
      variable-time schedules suppressed these rates. Although the overall rates later
      in the interval were not affected to any great extent, the fixed brief-stimulus
      schedules generated patterns of positively accelerated responding between
      stimulus presentations. These patterns appeared less frequently under the
      variable brief-stimulus schedules. Initially, when not paired with food delivery,
      presentations of the brief stimulus produced relatively little effect on either
      response rate or patterning. However, once the stimulus had accompanied food
      presentation, the original performance under the nonpaired condition was not
      recovered. The effects were more like those occurring when the stimulus was
      paired with food.

PMID- 16811756
TI  - Intercurrent and reinforced behavior under multiple spaced-responding schedules.
AB  - Lever pressing in rats was reinforced with food under a multiple spaced
      responding schedule. A lever, food cup, and drinking tube were mounted in a
      running wheel so that lever pressing, running, and licking could be recorded.
      Running and licking had no scheduled consequences. Lever pressing was reinforced
      under a multiple schedule with three spaced-responding components and an
      extinction component. Each component was associated with a different auditory
      stimulus. Spaced-responding components reinforced only lever presses terminating
      interresponse times equal to or greater than 10, 20, or 60 sec, respectively.
      Rates of lever pressing, reinforcement, and licking all decreased as schedule
      parameter increased. Efficiency of spaced responding, as measured by
      reinforcements per response, also decreased. Rate of wheel running either
      increased or increased and then decreased with increasing schedule parameter.
      Individual running rates differed substantially. Neither licking nor running rate
      correlated with individual differences in efficiency. Analysis of conditional
      probabilities among the several response classes showed that, as the schedule
      requirement increased, the probability of running after a lever press increased
      and the probability of licking after a lever press decreased. After
      reinforcement, one subject always pressed the lever next. In the other subjects,
      the conditional probability of lever pressing, given reinforcement, increased
      while the probability of licking, given reinforcement, decreased with increasing
      schedule requirement. Results are discussed in relation to the concepts of
      schedule-induced and mediating behavior.

PMID- 16811757
TI  - The effect of physical restraint on behavior under the differential-reinforcement
      of-low-rate schedule.
AB  - Previous studies have identified and manipulated collateral behavior to assess
      the effect of collateral behavior on performance under the differential
      reinforcement-of-low-rate (DRL) schedule. However, conclusions could not be
      applied to subjects not observed to engage in collateral behavior. The present
      study used a technique that prevented the occurrence of the types of collateral
      behavior typically observed in the pigeon. This technique did not require the
      identification of collateral behavior in the subjects. The exclusion of the types
      of collateral behavior typically observed in pigeons resulted in higher response
      rates and lower reinforcement rates under large DRL values but had no effect at
      lower DRL values. It was concluded that collateral behavior is necessary for low
      response rates and high reinforcement rates under large DRL values.

PMID- 16811758
TI  - Preference for intermittent reinforcement.
AB  - Two experiments were conducted demonstrating that under certain conditions
      pigeons may peck at a higher rate on a key that produces intermittent
      reinforcement following a delay than on one that always produces reinforcement
      following the same delay duration. In both experiments, concurrent chain
      schedules were employed. In Experiment I, a single peck on one key led to a white
      light and a delay of 15 sec, which always terminated with food. A peck on the
      other key led to its illumination by one of two colored lights and a delay period
      of 15 sec. The delay was followed by either food presentation or timeout, either
      one lasting 3 sec. In a control group, the lights on this key were not correlated
      with food or timeout. Under the correlated stimuli, birds more often pecked the
      key leading to intermittent reinforcement, whereas with uncorrelated stimuli they
      pecked the key leading to the white light and 100% reinforcement. In Experiment
      II, concurrent variable-interval schedules were employed in the first link. The
      results showed generally that the relative rate was higher on the key leading to
      intermittent reinforcement when the stimuli were correlated with reinforcement
      and timeout than on the key leading to 100% reinforcement. There was some
      indication that this performance was affected by (1) the duration of the delay,
      (2) the percentage of reinforcement on the key yielding the higher percentage of
      reinforcement (the key with the white light), and (3) prior experimental
      conditions.

PMID- 16811759
TI  - High-order concept formation in the pigeon.
AB  - After 30 days of operant training, with pecking responses to aerial photographs
      containing man-made objects reinforced with food, and no food reinforcement for
      pecking on photographs not containing man-made objects, a discrimination to the
      two classes of photographs was obtained. The discriminative response generalized
      to photographs with which the pigeons had no previous experience. This study
      demonstrates that pigeons are capable of forming relatively high-order concepts.
      Some possible stimulus properties controlling the discrimination are discussed.

PMID- 16811760
TI  - Impulse control in pigeons.
AB  - Pigeons were given a small, immediate food reinforcement for pecking a key, and a
      larger, delayed reinforcement for not pecking this key. Most subjects pecked the
      key on more than 95% of trials. However, when pecking a differently colored key
      at an earlier time prevented this option from becoming available, three of 10
      subjects consistently pecked it, thereby forcing themselves to wait for the
      larger reward. They did not peck the earlier key when it did not prevent this
      option. This is an experimental example of psychological impulse and a learnable
      device to control it. Although only a minority of the subjects learned it, the
      fact that such learning is possible at all argues for a theory of delayed reward
      that can predict change of preference as a function of elapsing time.

PMID- 16811761
TI  - Time allocation and response rate.
AB  - Food reinforcement for key pecking by three pigeons was arranged by a variable
      interval schedule and a device that assigned each reinforcement to one of 10
      component response rates corresponding to 10 classes of equally reinforced
      interresponse times ranging from 1.0 to 6.0 sec in 0.5-sec classes. The overall
      number of reinforcements per hour was varied from one to more than 60. Overall
      response rate was a monotonically increasing, negatively accelerated function of
      the overall number of reinforcements per hour. This function was decomposed into
      two time-allocation functions: (1) the time allocated to all of the reinforced
      component response rates as a function of the total reinforcement rate, and, (2)
      the time allocated to a particular reinforced component response rate as a
      function of the reinforcement rate for that component. Asymptotic response rate
      was predicted by combining the asymptotes of the two separate time-allocation
      functions: virtually all of the time was spent responding, and the percentage of
      the time spent responding that was allocated to a particular reinforced component
      response rate roughly equalled the relative reinforcements per hour for that
      component.

PMID- 16811762
TI  - Inhibitory stimulus control and the magnitude of delayed reinforcement.
AB  - The key pecking of pigeons was reinforced according to a variable-interval 1-min
      schedule during each of two successively presented stimuli. When the key was
      illuminated by a black line on a white background, reinforcement was delayed for
      10 sec. When the key was illuminated by a plain white light, reinforcement was
      not delayed. For half of the subjects, the delayed reinforcer was 4.0-sec access
      to mixed grain, and for the remaining subjects it was 1.5-sec access. The
      immediate reinforcer was 1.5-sec access for all subjects. All subjects responded
      at a lower rate during the presentation of the black line; no between-group
      difference in terms of terminal response rate during the presentation of the line
      was found. However, subjects that received 4.0 sec of delayed reinforcement
      responded at a lower terminal rate during presentation of the plain white light
      than subjects that received 1.5 sec of delayed reinforcement. A subsequent
      generalization test along the line-orientation dimension produced flatter U
      shaped gradients for subjects that received 4.0-sec of delayed reinforcement.

PMID- 16811763
TI  - Topography of the food-reinforced key peck and the source of 30-millisecond
      interresponse times.
AB  - High-speed photography of key pecking revealed that the arc described by the
      upper bill as a pigeon closes its beak is capable of operating a Lehigh Valley
      pigeon key set at 8 to 14 g. Arc-produced switch closure follows initial switch
      closure in less than 50 msec. When birds were trained on ratio schedules, the
      probability of interresponse times (IRTs) shorter than 50 msec exceeded 0.30.
      Interval-trained birds produced a much lower probability of short-IRTs. When the
      schedules were reversed, there was only weak evidence of a reversal in the
      probability of short IRTs. A temporal analysis of topographic features observed
      in the original photographs failed to reveal differences between ratio and
      interval pecking topography. It appeared that only the point of contact with the
      key differed between subjects trained on the two schedules. It was concluded that
      only the locus, but not the topography, of the food-reinforced key peck was
      modified by the schedule of reinforcement.

PMID- 16811764
TI  - Development and maintenance of attack in pigeons during variable-interval
      reinforcement of key pecking.
AB  - Key-peck responses of two pigeons were maintained on variable-interval schedules
      of food reinforcement in the presence of a stuffed pigeon to study the
      characteristics of attack induced by that schedule. The mean interval of the
      schedule was increased from 15 sec to 600 sec in eight steps before an
      intermediate interval was reintroduced. The principal characteristics of attack
      were: (1) substantial attack first occurred on a variable-interval schedule of 90
      sec in one pigeon and at 180 sec in the other, (2) the highest attack rates
      occurred on variable-interval schedules of 300 sec and 600 sec, (3) attack rate
      generally increased to a maximum and then decreased to a lower level across
      sessions at each schedule, (4) attacks developed a postreinforcement locus across
      the initial sessions on all schedules and, except on variable-interval schedules
      of 300 and 600 sec, occurred primarily in the postreinforcement period during
      extended training, (5) attack rates and key-peck rates were not recovered when
      the intermediate-length schedules were reintroduced, and (6) attack rate and key
      peck rates were negatively correlated. Except for the fact that the maximum
      attack rates occurred at interfood intervals of 300 and 600 sec, and that attack
      and key-peck rates were negatively correlated, these findings have counter-parts
      in experiments with other reinforcement schedules.

PMID- 16811765
TI  - Pictorial target control of schedule-induced attack in White Carneaux pigeons.
AB  - Three pigeons with a history of attacking a mirror target, and two of six pigeons
      with no prior exposure to targets, attacked a colored photograph of a conspecific
      during exposure to intermittent schedules of reinforcement for key pecking. Rate
      of attack on the photograph decreased when the reinforcement schedule was
      removed. The topography, temporal pattern, and locus of attack on the picture
      were comparable to schedule-induced attack on live, stuffed, and mirror targets.
      When silhouette, outline, and plain paper targets were used, schedule-induced
      attack was more sensitive to a change in target characteristics with a concurrent
      target-preference procedure than with an analogous successive-testing procedure.
      The combined results of the two testing procedures indicated that an "upright"
      white-on-black silhouette of a pigeon with or without an eye was more effective
      in controlling attack than was a comparable "inverted" silhouette, an outline of
      a pigeon, or a piece of colored paper.

PMID- 16811766
TI  - Time-allocation, matching, and contrast.
AB  - A variable-interval schedule arranged food reinforcement for key pecking by
      pigeons on a single operandum at two rates, corresponding to two classes of
      reinforced interresponse times ranging from 1.5 to 2.5 sec and from 3.5 to 4.5
      sec. The scheduled reinforcement rate for the higher component response rate was
      constant and equivalent to that of a variable-interval 4-min schedule. The
      scheduled reinforcement rate for the lower component response rate varied from
      zero to over 100 per hour. The number of occurrences of the constant component
      response rate varied inversely with the reinforcement rate for the variable
      component. This result, by definition a concurrent reinforcement interaction, or
      contrast, was the combined effect of two time-allocation functions, which
      together determine mean response rate: the time allocated to both component rates
      as a function of the total reinforcement rate, and the time allocated to a
      particular component rate as a function of the percentage of reinforcements for
      that component. The present experiment reveals a further parallel between the
      controlling relations for free responding on a single operandum and those for
      choice between two operanda; in each case, a concurrent reinforcement interaction
      can be found that corresponds to matching.

PMID- 16811767
TI  - Response-produced timeouts under a progressive-ratio schedule with a punished
      reset option.
AB  - Three behavioral options were available to food-deprived pigeons: (1) pecking one
      key resulted in food reinforcement according to a 50-response progressive-ratio
      schedule, (2) pecking a second key reset the progressive-ratio schedule to the
      initial progressive-ratio step, and (3) pecking a third key produced a 3-min
      timeout period. Pecks on the reset key were shocked. Under low and intermediate
      shock intensities, timeouts were not produced; under high shock levels, timeouts
      were produced regularly. Timeouts occurred during the initial period of a
      progressive-ratio step and were more frequent during the longer steps of the
      progressive-ratio schedule. Response-produced timeouts under these experimental
      conditions could be interpreted either as an escape from aversive behavioral
      options or as a low-probability behavior emerging when the food reinforcement
      schedule exerted weaker control.

PMID- 16811768
TI  - Preference for fixed-interval terminal links in a three-key concurrent chain
      schedule.
AB  - Pigeons were trained on three-key concurrent chain schedules in which the initial
      links were variable-interval schedules and the terminal links were fixed-interval
      schedules. In the first experiment, the initial links were all equal and the
      terminal-link schedule on one key only was varied. In the second part of the
      experiment, the terminal-link schedules were all fixed, but different, and the
      initial-link schedule on one key was varied. Relative response rates in the
      initial links did not match either the relative arranged, nor the relative
      obtained, terminal-link reinforcement rates. The relations between independent
      and dependent variables in three-key concurrent chains were similar to, but not
      identical with, those found in two-key chains comprising the same schedule types.

PMID- 16811769
TI  - The effects of number of responses on pause length with temporal variables
      controlled.
AB  - A change in the size of a fixed-ratio schedule involves a simultaneous change in
      number of responses, in time to complete the ratio (work time), and in the
      interval between successive reinforcements (interreinforcement interval).
      Previous studies have suggested the importance of work time and the
      interreinforcement interval in controlling the length of the post-reinforcement
      pause. The present study sought to determine whether number of responses is also
      a significant factor. Pigeons were trained on a multiple fixed-ratio x fixed
      ratio 2 plus timeout schedule in which the size of the fixed-ratio x was
      manipulated. When the work times (Experiment I) or interreinforcement intervals
      (Experiment II) were equated for the two components, the pause before the fixed
      ratio x was longer than the pause before the fixed-ratio 2 plus timeout. As fixed
      ratio x size increased, the relative difference in the lengths of the two types
      of pauses also increased. Because the fixed-ratio x component contained a larger
      number of responses than the fixed-ratio 2 plus timeout component, the relatively
      longer pause preceding the fixed-ratio x indicates that number of responses
      played a significant role in determining the length of the post-reinforcement
      pause.

PMID- 16811770
TI  - Behavior under large values of the differential-reinforcement-of-low-rate
      schedule.
AB  - Pigeons pecked a key and rats pressed a lever for food reinforcement under large
      values of the differential-reinforcement-of-low-rate schedule. Each subject was
      tested under 10 different schedule values ranging from 1 to 45 min and was
      exposed to each schedule value at least twice. The mean interresponse time and
      mean interreinforcement time increased with the schedule value according to power
      functions. Response-probability functions were computed for schedule values below
      20 min and showed an increase in response probability as a function of time since
      the last response in most cases. Mean responses per reinforcer increased as a
      function of schedule value for the rats, but decreased as a function of schedule
      value for the pigeons. The proportion of responses with interresponse times
      shorter than 1 sec were an increasing function of schedule value for the pigeons,
      but did not vary as a function of schedule value for the rats.

PMID- 16811771
TI  - Control of key pecking by the duration of a visual stimulus.
AB  - Pigeons' key pecks were brought under the control of the duration of a visual
      stimulus in one-key and two-key procedures. In the one-key procedure, pecks were
      reinforced after presentations of a long-duration stimulus but not after
      presentations of a short-duration stimulus. In the two-key procedure, left-key
      pecks were reinforced after the long-duration stimulus and right-key pecks after
      the short-duration stimulus. In both procedures, the long-duration stimulus was
      10 sec, and the short-duration stimulus was increased from 1 to 8 sec in 1-sec
      steps. Discriminative control developed with both procedures, but with greater
      accuracy in the two-key procedure, in which a difference threshold was obtained
      at short-duration values between 7 and 8 sec, or about 2.5 sec shorter than the
      long-duration stimulus.

PMID- 16811772
TI  - Patterning with fixed-time schedules of response-independent reinforcement.
AB  - Pigeons were first exposed to a schedule providing food when the time between
      successive key pecks (the interresponse time) exceeded a specified duration. When
      food then was presented at regular intervals independent of responding (fixed
      time schedule), responses typically occurred at a steady rate in the periods
      between successive food presentations. Once the birds had been exposed to a fixed
      ratio schedule, however, response rate under fixed-time schedules was positively
      accelerated. Variations in the sequence of conditions given different subjects
      indicated that the changes in patterning were due to the fixed-ratio schedule,
      rather than to the number of transitions from a response-dependent to the
      response-independent fixed-time schedule, to changed parameter values, or to
      prolonged experience with the fixed-time schedule. The effects of fixed-time
      schedules on patterning depended upon experimental history.

PMID- 16811773
TI  - Preference for signalled reinforcement.
AB  - Key pecking was reinforced on a two-component multiple schedule. A variable
      interval schedule controlled reinforcement in both components. During one
      component, access to reinforcement was preceded by a tone; in the other
      component, a standard unsignalled schedule was in effect. After performance
      stabilized, subjects were given a choice between the signalled and unsignalled
      schedules. They were placed in the chamber with the unsignalled schedule in
      effect on the right key. A single response on the left, or changeover, key
      produced the signalled schedule for 1 min. Both pigeons in Experiment I pecked
      the changeover key at a rate sufficient to remain under the signalled schedule
      for over 90% of the session. Removing and reintroducing the tone demonstrated
      that the changeover-key responses were due to the occurrence of the tone. In
      Experiment II, when pecking the changeover key produced the unsignalled schedule,
      pecking the changeover key declined. The results may be explained either in terms
      of Hendry's information hypothesis or as escape from an intermittent positive
      reinforcement schedule.

PMID- 16811774
TI  - On the nature of non-responding in discrimination learning with and without
      errors.
AB  - In human subjects, discrimination learning with errors results in active
      responding incompatible with the reinforced response. The direction of such
      incompatible behavior is opposite to that of the reinforced response. Responding
      occurs only during the stimulus correlated with extinction. The frequency of
      active non-responding is maximal shortly after the start of discrimination
      training (the time at which the frequency of errors decreases most rapidly) and
      approaches zero as discrimination training continues. The magnitude of behavioral
      contrast is not related systematically to the number of errors. Instead it is
      related directly to the frequency of active non-responding. Active non-responding
      appears to be motivated by the aversiveness of self-produced frustration, in the
      sense that active non-responding allows the subject to avoid the aversiveness of
      non-reinforced responding.

PMID- 16811775
TI  - Discriminative effects of massed extincttion.
AB  - Prior studies have reported that generalization gradients are not steepened if
      periods of non-reinforcement in S- follow and are not interspersed with periods
      of reinforcement in S+. Sharper gradients are produced by this massed-extinction
      procedure if it is preceded by prior discriminative training on a dimension
      orthogonal to the S+, S- dimension. The present study, using pigeons, found that
      generalization gradients along the wavelength dimension were steepened by massed
      extinction sessions in 570 nm that had been preceded by: (1) discriminative
      training in which the S+ was a 550-nm light and the S- was a black vertical line
      superimposed on the 550-nm light; (2) non-differential reinforcement training
      with a 550-nm light and a black vertical line superimposed on the 550-nm light;
      (3) reinforcement training with only the 550-nm light. Massed-extinction sessions
      were administered until the response rate in the presence of the 570-nm stimulus
      was one-tenth of the mean response rate in the presence of the 550-nm stimulus
      during prior reinforcement training. Prior studies have used a time-dependent
      criterion, rather than a response-rate criterion of extinction, and this
      difference may be responsible for the differences in the effects of massed
      extinction on stimulus control.

PMID- 16811776
TI  - Two unlike patterns of random-ratio responding associated with different eating
      habits in rhesus monkeys.
AB  - Four rhesus monkeys were exposed to an identical series of schedules that
      specified a uniform probability of reinforcement for every response. As
      probability was lowered slowly in 10 steps of 20 sessions each from 1.0 through
      0.01, two distinct patterns of responding emerged. Two subjects showed high,
      pause-free response rates that increased with each successive reduction in
      reinforcement probability. The other two showed consistent post-reinforcement
      pausing at all probabilities, including 1.0, and substantially lower response
      rates that peaked at the moderate probability values of 0.04 and 0.03. This low
      rate pattern was found to be correlated with a pre-experimental preference in the
      two subjects for mouthing and chewing food pellets one at a time, while the
      former high-rate, pause-free pattern was linked to a long-standing habit of
      "pouch feeding" in the other monkeys. These idiosyncratic collateral behaviors
      that differentiated the schedule performances appeared neither superstitious in
      origin, nor useful in the case of the low-rate monkeys.

PMID- 16811777
TI  - Induced attack during multiple fixed-ratio, variable-ratio schedules of
      reinforcement.
AB  - TWO PIGEONS WERE EXPOSED TO A MULTIPLE SCHEDULE OF REINFORCEMENT: in the presence
      of one discriminative stimulus, key pecks produced grain according to a fixed
      ratio schedule; in the presence of a second discriminative stimulus, key pecks
      produced grain according to a variable-ratio schedule. The key-peck requirements
      in the two components were increased in successive stages from 50 to 125
      responses. Live target pigeons were restrained at the rear of the chamber.
      Attacks against the targets were automatically recorded, and a variety of
      measures of attack behavior were taken. Attacks, when they occurred, always
      followed grain presentation. All measures revealed higher levels of attack during
      the fixed-ratio component at all parameter values. All measures generally
      increased with increases in fixed-ratio values with both birds, and with
      increases in variable-ratio values with one bird. With the other bird, only the
      per cent of reinforcements followed by attack increased with increases in
      variable-ratio value; all other measures first increased and then decreased. Both
      increasing and bitonic functions relating induced attack to schedule parameters
      have been reported in experiments usually employing a single measure of attack.
      The measures have varied widely among these experiments. It is suggested that
      further studies of induced attack examine a wider range of schedule parameters
      and that relationships among measures be studied.

PMID- 16811778
TI  - Effects of response-dependent and independent electric shock on schedule-induced
      polydipsia.
AB  - In Experiment I, lever pressing by rats was maintained by the delivery of food
      pellets under a 45-sec fixed-interval schedule. Fixed-time 180-sec and fixed
      interval 180-sec schedules of shock delivery were systematically superimposed on
      the baseline food schedule to study effects on schedule-induced water intake.
      Response-dependent shock had little, if any, effect on water intake, whereas
      shocks independent of lever pressing attenuated fluid intake. In Experiment 2,
      rats received food pellets under a fixed-time 60-sec schedule. Electric shock
      delivered concurrently under a variable-time 180-sec schedule, but never while
      the animal was licking or within 5 sec after licking terminated, led to similar
      attenuation of water intake. These findings suggest that schedule-induced
      polydipsia is sensitive to differences in the functional properties of response
      independent and dependent electric shock.

PMID- 16811779
TI  - A yoked-chamber comparison of concurrent and multiple schedules: the relationship
      between component duration and responding.
AB  - Two experimental chambers were electrically connected so that the component
      selected by a pigeon confronting concurrent variable-interval schedules in one
      chamber could be successively presented as a multiple schedule to a second pigeon
      in the other chamber. Component duration was regulated by the use of a changeover
      delay, the value of which was systematically varied between 0 and 30 sec. It was
      found that the relative local response rates on the preferred key (absolute
      response rate to that component divided by the sum of the absolute response rates
      during both components) tended to increase with increasing component durations
      for the birds in the concurrent chamber, but decreased for the birds in the
      multiple chamber. These data support the interpretation that there are
      fundamental differences in the mode of responding to multiple and concurrent
      schedules. Based on these findings, it was concluded that previous demonstrations
      of matching on multiple schedules do not establish that response allocation is
      controlled by a process equivalent to that found on choice paradigms. It now
      appears that matching on multiple (but not concurrent) schedules is a consequence
      of selecting short component durations. The implications of these data for
      Herrnstein's (1970) and Rachlin's (1973) formulations of the relationship between
      multiple and concurrent schedules are examined.

PMID- 16811780
TI  - Key pecking as a function of response-shock and shock-shock intervals in
      unsignalled avoidance.
AB  - Five pigeons were exposed to an unsignalled avoidance procedure where key pecks
      were maintained through shock postponement. Functions obtained showed an inverse
      relationship between rate of responding and length of the response-shock
      interval, while changes in the shock-shock interval had no systematic effect on
      response rates. The rate of shocks delivered generally decreased with increases
      in length of both response-shock and shock-shock intervals. Results show that key
      pecking in pigeons, maintained through an unsignalled avoidance procedure, was
      affected by changes in response-shock and shock-shock intervals in the same
      manner as other responses in pigeons and in rats.

PMID- 16811781
TI  - Free-operant escape-avoidance of noise by rats.
AB  - A series of experiments was conducted to establish free-operant escape-avoidance
      responding in rats using noise as the stimulus. Naive rats did not acquire a bar
      press response on an escape-avoidance of noise schedule. Similarly, free-operant
      responding established using escape-avoidance of shock was not maintained when
      noise was substituted for shock. Noise stimuli of 110 dB did maintain responding,
      but at a lower level than during training, when the noise stimuli had first been
      paired with shock. Noise stimuli of 97 dB and 87 dB were not effective under
      those same conditions. Additional rats were trained on a free-operant escape
      avoidance schedule of shock and then exposed to a delayed conditioning procedure
      in which noise was the conditioned stimulus and shock was the unconditioned
      stimulus. When these subjects were then tested with noise alone, two of the three
      subjects conditioned and tested with 105-dB noise displayed escape-avoidance of
      noise, but none of the rats conditioned and tested at 97 dB displayed escape
      avoidance of noise. The results suggest that free-operant escape-avoidance of
      noise can be demonstrated; however, only higher intensity noise stimuli that have
      been paired with shock are effective.

PMID- 16811783
TI  - The evaluation and control of acoustical standing waves.
AB  - Calibration of a standard pigeon box subsequently modified for use as an
      acoustical chamber in a frequency discrimination experiment revealed that the
      enclosure was not acoustically "flat". Standing waves were detected at each of
      the six frequencies measured. To ascertain whether the maximum standing waves
      recorded (3.0 dB) could serve as an added or alternative cue for pigeons tested
      in the chamber on a frequency discrimination problem, pure-tone intensity
      difference thresholds were determined for two pigeons at 1.0, 2.0, and 3.0 KHz.
      The results of the experiment indicated that the smallest intensity difference
      detectable was 10.0 dB, a value that was 7.0 dB above the maximum standing wave
      measured in the box. These data suggest that the modified pigeon chamber is
      suitable to test pure-tone frequency discriminations in pigeons in the range of
      1.0 to 3.0 KHz.

PMID- 16811782
TI  - On two types of deviation from the matching law: bias and undermatching.
AB  - DATA ON CHOICE GENERALLY CONFORM CLOSELY TO AN EQUATION OF THE FORM:
      log(B(1)/B(2))=a log(r(1)/r(2)+log k, where B(1) and B(2) are the frequencies of
      responding at Alternatives 1 and 2, r(1) and r(2) are the obtained reinforcement
      from Alternatives 1 and 2, and a and k are empirical constants. When a and k
      equal one, this equation is equivalent to the matching relation:
      B(1)/B(2)=r(1)/r(2). Two types of deviation from matching can occur with this
      formulation: a and k not equal to one. In some experiments, a systematically
      falls short of one. This deviation is undermatching. The reasons for
      undermatching are obscure at present. Some evidence suggests, however, that
      factors favoring discrimination also favor matching. Matching (a=1) may represent
      the norm in choice when discrimination is maximal. When k differs from one, its
      magnitude indicates the degree of bias in choice. The generalized matching law
      predicts that bias should take this form (adding a constant proportion of
      responding to the favored alternative). Data from a variety of experiments
      indicate that it generally does.

PMID- 16811784
TI  - An appraisal of preference for multiple versus mixed schedules.
AB  - Pigeons' choice responses on either of two keys occasionally produced entry into
      a terminal link associated with that key. During the terminal links, responses
      produced access to grain according to mixed- or multiple-interval schedules. The
      multiple schedules provided stimuli correlated with the interval of time
      preceding reinforcement whereas the mixed schedules did not. The two subjects
      reliably preferred the multiple schedules to the mixed schedules throughout a
      series of replications. Preference for the multiple schedule was much smaller
      than suggested by earlier work comparing multiple and mixed schedules that had
      much higher rates of entry into the terminal links. Preference for the multiple
      schedule was greatly increased in this study when the rate of entry into the
      terminal schedules was increased. As in previous studies, these high preferences
      may have been the result of a sharp increase in the number of reinforcements on
      the multiple (as opposed to the mixed) schedule. The reliable but smaller
      preferences for the multiple schedule found with lower rates of entry into the
      terminal links were unconfounded by differences in the number of reinforcements
      obtained in the two terminal links.

PMID- 16811785
TI  - The disruption of autoshaped key pecking in the pigeon by food-tray illumination.
AB  - Two experiments investigated the effect of food-tray illumination on pecking a
      lighted key that signalled food presentation. Pigeons key pecked less when both
      feeder and key stimuli preceded grain delivery than when the keylight alone
      signalled food. This detractive influence of grain-tray illumination did not
      result after prior pairings of the keylight with food. The involvement of
      associative and physical variables in autoshaping the pigeon's key peck is
      considered in light of these findings.

PMID- 16811786
TI  - Autoshaping: further study of "negative automaintenance".
AB  - The key pecking of pigeons was autoshaped to three key colors paired with food in
      discrete trials. Then, the effects of three different color-correlated
      contingencies were compared: reward (presentation of food contingent on pecking),
      omission (presentation of food prevented by pecking), and extinction (no food).
      Two measures of performance were used: initial response (the number of trials
      with each color on which at least one peck was made) and multiple response (the
      total number of pecks per trial). In general, the reward color produced more
      pecking than the omission color, the omission color more than the extinction
      color, and the extinction color more than on blank trials with an unlighted key,
      although (relative to reward) omission produced a higher level of initial than of
      multiple responding. These results point clearly to the importance of stimulus
      reinforcer continguity in the control of pecking.

PMID- 16811787
TI  - All-or-none-acquisition in matching-to-sample and a test of two models.
AB  - Three pigeons learned to match three colors in a matching-to-sample procedure.
      The sample hue was presented on the center one of three keys, and the comparison
      hues were presented on the side keys. Forty responses on the center key produced
      the stimuli on the side keys and left the sample on the center key. A single
      response on the correct side key produced 3-sec access to grain, which was
      followed by a 25-sec intertrial interval. A correction procedure was employed
      when an error was committed. Before attaining asymptotic levels, there was no
      evidence of learning, responses were independent of the preceding response, and
      distributions of errors in four-trial blocks were binomial. Distributions of
      error runs, runs of various lengths, autocorrelations of errors of several lags,
      alternations of correct responses and errors, etc., were shown to fit Bower's
      (1961) all-or-none model better than a gradual learning model of Bush and
      Sternberg (1959). A transfer test employing a novel color showed only transitory
      degradation of performance.

PMID- 16811788
TI  - Effects of the difference between self and coactor scores upon the audit
      responses that allow access to these scores.
AB  - An audit response allows access to an existing score from a subject's own
      performance (self audit) or from his coactor's performance (coactor audit). A
      previous study found that social stimuli (coactor present) increased audits
      relative to a non-social (no coactor) condition. The increase, designated a
      social-stimulus effect, was found to be due more to the coactor's score than to
      his mere presence. This finding suggested that the difference between self and
      coactor scores might affect the size of the social-stimulus effect. In the
      present study, six pairs of human subjects matched-to-sample for points that were
      exchangeable for money. During a session, matching-to-sample problems were
      distributed so that a subject's score was ahead, behind, or about even with his
      coactor's score. The even condition produced the largest social-stimulus effects,
      i.e., the most audits that could not be attributed to non-social variables such
      as time or number of problems. The even condition may have produced the largest
      social-stimulus effects because it was the only condition where the major social
      reinforcer (being ahead) could be both present or absent and, consequently, the
      even condition was the only one where audits had a discriminative function with
      respect to the presence of the major social reinforcer.

PMID- 16811789
TI  - Temporal inhibition: effects of changes in rate of reinforcement and rate of
      responding.
AB  - Pigeons were trained to key peck on several multiple schedules in which the first
      of two components was always a simple fixed-interval schedule. The rate of
      responding at the beginning of the constant fixed-interval schedule was found to
      decrease with increases in the rate of reinforcement associated with the other
      component of the multiple schedule, but remained unchanged with decreases in the
      rate of responding associated with the other component. These results were
      interpreted as being consistent with the view that the presence and magnitude of
      the temporal inhibitory effects observed in a given fixed-interval schedule are a
      function of the properties of reinforcing stimuli, rather than of changes in the
      rate of responding associated with the time interval immediately preceding the
      fixed interval in question.

PMID- 16811790
TI  - Negatively reinforced key pecking.
AB  - A reinforcement-switching procedure was used to produce negatively reinforced key
      pecking in pigeons. First, key pecking on a chain schedule (fixed-interval 10-sec
      variable-interval 60-sec) was conditioned using grain reinforcement. Second,
      intermittent shock in the initial link was introduced at a low intensity and
      gradually increased. Third, food reinforcement in the terminal link was
      eliminated. With shock at 90 V occurring on the average every 3 sec, initial-link
      pecking was maintained with no terminal-link food. Three of four pigeons
      responded consistently at shock intensities of 90, 70, and 50 V but not at 30 V.
      A fourth pigeon responded at but not below 90 V. Rate of response was directly
      related to shock frequency. Eliminating food deprivation did not affect the
      negatively reinforced performance.

PMID- 16811791
TI  - Chained concurrent schedules: reinforcement as situation transition.
AB  - Pigeons' pecks at two white response keys (initial-link situation) occasionally
      turned both keys red (terminal-link situation). When the two keys were red, pecks
      occasionally produced food, after which the keys were again white. In both
      situations, a changeover delay prevented the response-produced outcome from
      immediately following a change of responding from either key to the other. In the
      initial-link situation, the ratio of pecks at the keys closely paralleled the
      ratio of transitions into the terminal-link situation produced by the pecks,
      conforming to the well-known matching relation. In the terminal-link situation,
      the peck ratios deviated from the matching relation toward indifference. Overall
      response rate and rate of changeover were generally higher in the terminal-link
      situation than in the initial-link situation. The finding of matching in the
      initial-link situation supports a definition of reinforcement as situation
      transition. The differences in performance between the two situations, viewed in
      the light of other recent findings, suggest that the effects of a changeover
      delay depend on the overall reinforcing value of the choice alternatives.

PMID- 16811792
TI  - Transfer of control of the pigeon's key peck from food reinforcement to avoidance
      of shock.
AB  - Eight pigeons were initially trained to peck a white key for food under a
      variable-interval 1-min schedule of reinforcement. Then, a shock-avoidance
      schedule was initiated and food was no longer available in the experimental
      situation. Under the avoidance schedule, each peck on the key postponed shock for
      40 sec. A warning signal, consisting of tone and red houselights, was presented
      after 30 sec without a response. If no response occurred, a shock was delivered
      10 sec after warning-signal onset. Shocks were delivered every 10 sec in the
      presence of the warning signal until a response was made. The warning signal was
      terminated only by a response. Key pecking of all eight pigeons came under
      control of the avoidance schedule and responding continued throughout the 20-day
      avoidance training period.

PMID- 16811793
TI  - Differentiation of press durations with upper and lower limits on reinforced
      values.
AB  - Rats received food following lever-press durations between t and t+t' sec where t
      was 2, 4, or 8 sec and t' was 0.25t, 0.50t, or 1.00t sec. Modal press durations
      were greater than t but less than t+t' in all cases. Distributions of press
      durations were lower and broader for larger values of t. Lower t'/t ratios
      produced lower median press durations and relatively narrower press-duration
      distributions. Median press duration was a power function of t within a t'/t
      ratio condition, corresponding to previous results for latency, interresponse
      time, and response durations.

PMID- 16811794
TI  - Time limits for completing fixed ratios. III. Stimulus variables.
AB  - Pigeons received food only if they took longer than a specified time to begin and
      complete a fixed ratio. In Experiment 1, ratios with shorter durations had no
      stimulus consequence; in Experiment 2, these ratios ended with a stimulus change.
      In both studies, the mean time to complete the ratio exceeded requirements of
      less than 30 sec, approximately matched requirements of 30 sec, and fell
      progressively short of matching thereafter. Variability increased together with
      the means. The various effects resembled those of temporal differentiation
      experiments involving single responses. Although both number of ratios and time
      separating successive food presentations increased along with ratio duration,
      control experiments showed that differential reinforcement of duration, rather
      than either form or reinforcer intermittency, accounted for the performance.
      Experiment 2 also studied the effects of adding a stimulus that signalled when
      the required time had elapsed. The stimulus produced durations that matched even
      the most stringent requirements. This precision was not maintained when the
      stimulus was removed. Temporal differentiation schedules seem to have similar
      effects regardless of the response class and temporal property involved.

PMID- 16811795
TI  - Effects of random reinforcement sequences.
AB  - Rats were exposed to a random sequence of reinforcement on two levers, such that
      there was no way to predict from the previous reinforcement which lever would
      deliver reinforcement next. The rats showed a tendency to repeat the choice that
      had just produced reinforcement, despite the absence of an overall contingency
      that differentially reinforced such repetition. However, this tendency decreased
      with continued exposure to the schedule. Runs of successive reinforcements on a
      lever increased the probability of pressing that lever, but only slightly, and
      only in the earlier phases of training. The more quickly a press was made after
      reinforcement the more likely it was to be on the lever that had delivered that
      reinforcement. Repetition of choice followed by reinforcement should be viewed as
      a naturally occurring behavior in the rat, but not necessarily as a behavior that
      will continue without differential reinforcement of repetition.

PMID- 16811796
TI  - Motivation in concurrent variable-interval schedules with food and water
      reinforcers.
AB  - The lever pressing of four food- and water-deprived rats was reinforced on
      concurrent variable-interval schedules. Food reinforced one response, and water
      reinforced the other. Response rates in baseline were higher in the food
      component than in the water component. After response patterns and body weights
      had stabilized, the animals were given access to either food only, water only,
      both food and water, or neither food nor water (baseline) before daily sessions.
      Giving food before a session decreased per cent time in the food component,
      decreased overall response rates for food, and increased overall response rates
      for water. Giving water before a session increased per cent time in the food
      component, increased overall response rates for food, and decreased overall
      response rates for water. Giving both food and water before a session resulted in
      a combination of prefeeding and prewatering effects. More food and more water
      were consumed when both were available than when only one was available before a
      session.

PMID- 16811797
TI  - Errorless discrimination established by differential autoshaping.
AB  - In Experiment I, pigeons exposed to a differential autoshaping procedure pecked a
      key in the presence of the stimulus associated with reinforcement but did not
      peck, or pecked infrequently, in the presence of the stimulus associated with
      nonreinforcement. In Experiment II, pigeons were exposed to a differential
      autoshaping procedure in which one stimulus was associated with reinforcement and
      two stimuli were associated with nonreinforcement. The birds initially responded
      in the presence of one stimulus associated with nonreinforcement but never
      responded in the presence of the second stimulus associated with
      nonreinforcement. They were subsequently exposed to an autoshaping procedure in
      which reinforcement followed both these stimuli. The number of stimulus
      reinforcement pairings required to establish pecking in the presence of the
      stimulus during which responses had not previously occurred suggested that such
      stimuli are inhibitory. These findings have implications for autoshaping,
      errorless discrimination, inhibition, and theories of discrimination byproducts.

PMID- 16811798
TI  - Centrifugal selection of signal-directed pecking.
AB  - Pigeons were exposed to a schedule of stimulus-correlated food presentations.
      When key pecks terminated trial signals and cancelled the delivery of food,
      pecking was either gradually or rapidly redirected away from the keys, depending
      on whether the food-omission contingency was introduced from the outset or after
      exposure to a response-independent baseline. In all cases, the food-omission
      contingency substantially reduced or eliminated pecking at the keys.

PMID- 16811799
TI  - Combinations of response-reinforcer dependence and independence.
AB  - The contribution of the response-reinforcer dependency to the control of behavior
      was investigated. Pigeons were trained to key peck under a variable-interval
      schedule of reinforcement. With the total number and temporal distribution of
      reinforcer deliveries in experimental sessions constant, the effects of varying
      the percentage of response-independent reinforcement were examined. At different
      times, 100%, 66%, 33%, 10%, or 0% of the scheduled reinforcers were delivered
      dependent upon key pecking and the remainder were delivered independently of
      responding. Response rates were related to the percentage of response-dependent
      reinforcement with lower response rates associated with smaller percentages of
      response-dependent reinforcement. The results suggest that the response
      reinforcer relation exerts control over behavior in a manner similar to that
      exerted by other parameters of reinforcement.

PMID- 16811800
TI  - Combining stimuli signalling response-dependent food and shock.
AB  - Three rats were exposed to a multiple schedule in which separate presentations of
      light and tone alternated with periods during which light and tone were absent.
      In Phase 1, light and tone each signalled identical variable-interval schedules
      of food delivery. In Phase 2, light and tone signalled separate but concurrent
      variable-interval schedules of food and shock delivery. In both phases, the
      absence of light and tone was associated with the differential reinforcement of
      other behavior. Test presentations of light, tone, and a light-plus-tone
      combination indicated that in both phases, light-plus-tone controlled higher
      response rates than either light or tone alone. The combination continued to
      control enhanced responding even when the test stimuli signalled variable
      interval schedules of food and fixed-ratio schedules of shock. In these latter
      sessions, enhanced control by the combination increased shock frequency with no
      corresponding change in food frequency. Apparently, the level of behavior
      controlled by the absence of two single stimuli may be more important than the
      consequences of responding in determining the effects of combined-stimulus
      presentations.

PMID- 16811801
TI  - Signalled reinforcement in differential-reinforcement-of-low rate schedules.
AB  - At several fixed and variable minimum reinforced interresponse times, a stimulus
      was added to differential-reinforcement-of-low-rate schedules to signal the
      availability or nonavailability of reinforcement. As the minimum reinforced
      interresponse time increased, the rate of unreinforced responding decreased.
      Changing from fixed to variable minimum interresponse time in the basic
      differential-reinforcement-of-low-rate schedule further decreased the rate of
      unreinforced responding. Both effects were to some degree reversible. For fixed
      minimum reinforced interresponse times of 30 sec or shorter, most unreinforced
      responses terminated interresponse times just short of that required for
      reinforcement. The minimum reinforced interresponse time and the number of short
      response latencies (</=0.5 sec) to the onset of the signal were negatively
      correlated. Both of these analyses suggested that at values of 30 sec or shorter,
      the subjects discriminated the availability of the reinforcer more on the basis
      of time than on the basis of presence or absence of the signal.

PMID- 16811802
TI  - The effects of total darkness on schedule control.
AB  - The study investigated the effect of total darkness on the key pecking of pigeons
      under fixed-ratio, variable-ratio, fixed-interval, and variable-interval
      schedules of food reinforcement. Eight pigeons were divided into groups of two,
      with each group conditioned to peck under one of the four schedules of
      reinforcement. Under an ABAB procedure, all pigeons experienced alternating light
      and dark conditions. The house- and keylights were (a) maintained at full
      intensity for the first 30 one-hour sessions, (b) faded out and disconnected over
      Sessions 31 through 50, (c) totally illuminated for Sessions 51 to 60, and (d)
      disconnected again for the final 10 sessions. Responding under the ratio
      schedules increased from 20% to 108% in the dark and responding under the
      interval schedules in the dark decreased by 37% to 93%.

PMID- 16811803
TI  - Average uncertainty as a determinant of observing behavior.
AB  - After discrimination training on a multiple variable-interval extinction schedule
      of food reinforcement, pigeons were placed on the uncued or mixed version of the
      same schedule and allowed to make an optional "observing response" that converted
      the uncued schedule to the corresponding cued schedule by providing a 20-sec
      exposure to the appropriate discriminative stimulus. The schedule consisted of
      one hundred 40-sec components, and the probability that any one of them would be
      a variable-interval component was systematically varied between 0.00 and 1.00.
      The results showed that the amount of observing behavior was an inverted "U"
      function of the probability of the variable-interval component. Few observing
      responses occurred at probabilities of 0.00 or 1.00, and maximum responding
      occurred at a value less than 0.50.

PMID- 16811804
TI  - Relative and absolute density of reinforcement as factors influencing the peak
      shift.
AB  - Four groups of six pigeons each were given nondifferential training on multiple
      variable-interval variable-interval reinforcement schedules and then were
      switched to differential training involving a multiple schedule in which
      reinforcement density was reduced in one of the two components. The multiple
      schedules used in the four groups had mean interreinforcement intervals of 1 min
      and 1 min in the two components changed to 1 min, 5 min; 2.5 min, 2.5 min changed
      to 2.5 min, 5 min; 12 sec, 12 sec changed to 12 sec, 24 sec; and 12 sec, 12 sec
      changed to 12 sec, 60 sec. In subsequently administered wavelength generalization
      tests, some peak shifts were observed in each condition and occurred occasionally
      in the absence of behavioral contrast or rate reduction in the less-reinforced
      component. The best predictor of peak shift was a high proportion of total
      responses emitted during the more-reinforced component at the end of differential
      training.

PMID- 16811805
TI  - Behavioral contrast with multiple positive and negative stimuli on a continuum.
AB  - After an initial period of nondifferential training, six pigeons were trained on
      a go/no-go discrimination involving 12 line tilts from vertical clockwise to
      horizontal. Responses to the first six tilts (positive stimuli) were reinforced
      on a variable-interval one-minute schedule, whereas responses to the other six
      tilts (negative stimuli) were extinguished. During the first several
      discrimination sessions, the highest response rate was typically to one of the
      positive stimuli that was relatively close to the negative stimuli or at an
      intermediate distance, rather than to one of the positive stimuli most distant
      from the negative stimuli. This effect decreased with extended training up to 50
      or 80 sessions.

PMID- 16811806
TI  - Response rate, reinforcement frequency, and behavioral contrast.
AB  - Pigeons responded for food on a multiple schedule in which periods of green-key
      illumination alternated with periods of red-key illumination. When behavior had
      stabilized with a variable-interval 2-min schedule of reinforcement operating
      during both stimuli, low rates of responding (interresponse times greater than 2
      sec) were differentially reinforced during the green component. Conditions during
      the red stimulus were unchanged. Response rates during the green component fell
      without changing the frequency of reinforcement but there were no unequivocal
      contrast effects during the red stimulus. The frequency of reinforcement during
      the green component was then reduced by changing to a variable-interval 8-min
      schedule without reducing the response rates in that component, which were held
      at a low level by the spacing requirement. Again, the conditions during the red
      stimulus were unchanged but response rates during that stimulus increased. These
      results show that reductions in reinforcement frequency, independently of
      response rate, can produce interactions in multiple schedules.

PMID- 16811807
TI  - A modified shock-delivery system for quail.

PMID- 16811808
TI  - Behavioral contrast without response-rate reduction.
AB  - Behavioral contrast was obtained in two experiments, which both employed a
      standard free-operant successive discrimination (a multiple variable-interval
      extinction schedule), without the occurrence of reductions of response rate in
      the extinction component. In Experiment I, one group of four pigeons was trained
      on a multiple schedule in which one stimulus was associated with a variable
      interval schedule and the second stimulus with response-independent reinforcement
      on a free variable-interval schedule. Though by the end of this training three
      pigeons were responding very little to the second stimulus, when this stimulus
      was associated with extinction all subjects showed a contrast effect. In
      Experiment II, eight pigeons were trained extensively to respond to a single
      stimulus on a variable-interval schedule, before a second stimulus associated
      with extinction was introduced. This second stimulus was dissimilar to the
      initial stimulus and five pigeons never responded in its presence. Nevertheless,
      all pigeons showed a contrast effect and there was no evidence that the effect
      was smaller in errorless subjects or smaller than in a subsequent discrimination
      where all subjects made many errors. Both experiments indicated that response
      reduction in one component of a multiple schedule is not a necessary condition
      for the occurrence of contrast.

PMID- 16811809
TI  - Peak shift as a function of multiple schedules of reinforcement.
AB  - Pigeons were trained to respond to two stimuli on the wavelength continuum, 550
      nm and 570 nm, each correlated with an independent schedule of reinforcement. The
      multiple schedule component in effect during 550 nm (S1) was always a variable
      interval 1-min. During the 570-nm stimulus (S2) the second component of the
      schedule was either variable-interval 30-sec, 1-min, 2-min, 5-min, or extinction
      for different groups of birds. Generalization gradients were obtained after this
      training, with the following results: (1) response rate to S1 during training was
      related to the reinforcement frequency associated with S2; the distribution of
      responding during generalization testing was a function of the schedules of
      reinforcement used during training and the response rates they produced.
      Decreases in the relative frequency of reinforcement correlated with S2 resulted
      in increases in the distribution shift of responses away from S2 during
      generalization testing.

PMID- 16811810
TI  - Behavioral interactions in multiple variable-interval schedules.
AB  - In Experiment I, two groups of four pigeons each were exposed to multiple
      schedules in which one component was always a variable-interval schedule with a
      mean interreinforcement interval of 30 or 180 seconds. The other component was
      either an equal variable-interval schedule or extinction. Response rates in the
      unchanged component always increased when reinforcement was no longer scheduled
      in the changed component, and decreased in seven of eight cases when the variable
      interval schedule was re-introduced. The per cent rate change in the unchanged
      component was inversely related to the frequency of reinforcement and to the
      ongoing response rate in the unchanged component. Rate changes in the unchanged
      component were not consistently correlated with changes in any single feature of
      the relative-frequency interresponse-time distributions. In Experiment II, the
      same pigeons were exposed to variable-interval schedules and multiple variable
      interval variable-interval schedules with equal mean interreinforcement
      intervals. Response rates were similar under both conditions.

PMID- 16811811
TI  - Effects of varying the percentage of key illuminations paired with food in a
      positive automaintenance procedure.
AB  - Three pigeons were exposed to a positive automaintenance procedure in which each
      trial began with a brief tone followed by the transillumination of a small
      central area of the response key for 10 sec. Key illumination was followed by
      food on 100%, 50%, 25%, 12.5%, and 0% of the trials. The effects depended on the
      dependent variable observed. The mean rate of responding during key illumination
      rapidly increased and then decreased slightly as the percentage of key
      illuminations paired with food increased. The number of key illuminations during
      which at least one response occurred increased as a negatively accelerating
      function of the percentage of key illuminations paired with food, and the mean
      latency to the first response during the key illuminations decreased as a
      negatively decelerating function of the percentage condition. The mean rate of
      sustained responding during key illumination was not systematically affected by
      changes in the percentage conditions.

PMID- 16811812
TI  - Differential autoshaping to common and distinctive elements of positive and
      negative discriminative stimuli.
AB  - The learning by hungry pigeons of a discrimination between two successively
      presented compound visual stimuli was investigated using a two-key autoshaping
      procedure. Common and distinctive stimulus elements were simultaneously presented
      on separate keys and either followed by food delivery, S+, or not, S-. The
      subjects acquired both between-trial and within-trial discriminations. On S+
      trials, pigeons pecked the distinctive stimulus more than the common stimulus;
      before responding ceased on S- trials, they pecked the common stimulus more than
      the distinctive one. Mastery of the within-display discrimination during S+
      trials preceded mastery of the between-trials discrimination. These findings
      extend the Jenkins-Sainsbury analysis of discriminations based upon a single
      distinguishing feature to discriminations in which common and distinctive
      elements are associated with both the positive and negative discriminative
      stimuli. The similarity of these findings to other effects found in autoshaping
      approach to signals that forecast reinforcement and withdrawal from signals that
      forecast nonreinforcement-is also discussed.

PMID- 16811813
TI  - Lever-contact responses in rats: automaintenance with and without a negative
      response-reinforcer dependency.
AB  - Pairing the presentations of one lever (cueing lever) with food led to the
      acquisition and persistence of lever contacts by rats. This behavior did not
      occur with a second lever, which was presented randomly with regard to food
      delivery. This finding obtained whether food delivery was independent of cueing
      lever contacts (positive automaintenance) or dependent on the absence of cueing
      lever contacts (negative automaintenance). The general findings were: (1) cueing
      lever contacts on the positive automaintenance procedure occurred on a higher
      proportion of trials and at higher rates when contacts occurred than on the
      negative automaintenance procedure; (2) instances of the cueing lever's failure
      to support responding were more frequent on the negative than the positive
      automaintenance procedure; and (3) the topography and median contact duration of
      positively automaintained responding differed from negatively automaintained
      responding. These findings agree substantially with the automaintenance
      literature on pigeons, suggesting that similar processes may characterize
      automaintained responding in both pigeons and rats.

PMID- 16811814
TI  - Short-term memory in the pigeon: stimulus-response associations.
AB  - THREE PIGEONS PECKED FOR FOOD IN TWO EXPERIMENTS IN WHICH EACH TRIAL CONSISTED OF
      TWO PHASES: a study and a test phase. The study phase in Experiment I consisted
      of two stimulus-response pairs presented successively. Each pair consisted of the
      illumination of a left or right key (the stimulus) and a peck on the lighted side
      key (the response). The study phase in Experiment II consisted of three such
      pairs presented successively. A retention interval, varied between 0.1 and 4.0
      sec, separated the study phase from the test phase. The test phase of a trial
      began with the illumination of the center key by one of two (Experiment I) or
      three (Experiment II) colors. This color was the same as the stimulus element of
      one of the pairs in the study phase. A reinforcer was presented if a subject then
      emitted the response element of the indicated stimulus-response pair. The results
      provide information on the conditions that enable a pigeon to remember the
      responses most recently emitted in the presence of various stimuli. The results
      suggest an account of the maintenance of behavior that is temporally
      noncontiguous with reinforcement.

PMID- 16811815
TI  - Timing of avoidance responses by rats.
AB  - Three rats were trained on an unsignalled shuttlebox-avoidance task under three
      response-shock intervals (10, 20, and 40 sec). Under all conditions, subjects
      developed excellent temporal gradients of avoidance; that is, response rate was
      an increasing function of time since last response. Although the response rate at
      any given interval of time after the previous response was inversely related to
      the response-shock interval, there was an underlying similarity in the temporal
      gradients for the three intervals. In all cases, response rate relative to the
      maximum response rate was approximately equal to the proportion of the interval
      that had elapsed. This suggests that rats in unsignalled avoidance are estimating
      time from response completion, and that the units of the estimate are
      proportional parts of the response-shock interval.

PMID- 16811816
TI  - Additive and suppressive response summation with a chain schedule.
AB  - Rats responded in a two-segment (variable-interval variable-interval) chain
      schedule. In one experiment, three subjects had either clicker, light, or clicker
      plus light as terminal-segment stimuli. All three responded at the highest rate
      when clicker plus light were present, thus showing additive summation. For three
      other subjects, initial-segment stimuli were either clicker, light, or clicker
      plus light. Two subjects responded at the lowest rate when clicker plus light
      were present, thus showing suppressive summation. In a second experiment, three
      subjects had either clicker, light, or neither clicker nor light as terminal
      segment stimuli. None of these subjects showed reliable additive summation. Three
      other subjects had clicker, light, or neither as the initial-segment stimulus,
      and all three showed suppressive summation. Additive and suppressive summation
      both can be demonstrated with chain schedules, but stimulus parameters may be
      major variables in producing the effect.

PMID- 16811817
TI  - Context, observing behavior, and conditioned reinforcement.
AB  - Pigeons made observing responses for stimuli signalling either a fixed-interval
      30-sec schedule or a fixed-ratio x schedule, where x was either 20, 30, 100, 140,
      or 200 and the schedules alternated at random after reinforcement. If observing
      responses did not occur, food-producing responses occurred to a stimulus common
      to both reinforcement schedules. When the fixed-interval schedule was paired with
      a low-value fixed ratio, i.e., 20 or 30, the presentation of the stimulus
      reliably signalling the fixed-ratio schedule reinforced observing behavior, but
      the presentation of the stimulus reliably signalling the fixed-interval schedule
      did not. The converse was the case when the fixed-interval schedule was paired
      with a large-valued fixed ratio, i.e., 100, 140, or 200. The results demonstrated
      that the occasional presentation of the stimulus signalling the shorter
      interreinforcement interval was necessary for the maintenance of observing
      behavior. The reinforcement relationship was a function of the schedule context
      and was reversed by changing the context. Taken together, the results show that
      the establishment and measurement of conditioned reinforcement is dependent upon
      the context or environment in which stimuli reliably correlated with differential
      events occur.

PMID- 16811818
TI  - Temporal control of periodic schedules: signal properties of reinforcement and
      blackout.
AB  - Pigeons were exposed to periodic food-reinforcement schedules in which intervals
      ended with equal probability in either reinforcement or brief blackout. The
      effects on the pattern of key pecking of sequential probability of reinforcement,
      interval duration, and time to reinforcement opportunity were investigated in
      three experiments. The major results were: (1) at short absolute interval
      durations, time to reinforcement opportunity determined both postreinforcement
      and postblackout pause (time to first key peck within an interval); (2) at long
      intervals, postblackout pause was consistently shorter than postreinforcement
      pause, even if both events signalled the same time to the next reinforcement
      opportunity (omission effect); (3) when reinforcement and blackout signalled
      different times to the next reinforcement opportunity, within the same
      experiment, there was some evidence for interactions analogous to behavioral
      contrast.

PMID- 16811819
TI  - Fixed-ratio discrimination: effects of response-produced blackouts.
AB  - For three pigeons, reinforcement depended upon a left side-key response after
      execution of a fixed ratio 10 on the center key, and upon a right side-key
      response after fixed ratio 20. Each response during the fixed ratios produced a
      0.5-sec blackout. The time between the first and last response in fixed ratio 10
      was then equated with the time between the first and last response in fixed ratio
      20 by increasing the blackout duration. The accuracy of side-key choice was
      disrupted, thereby suggesting that time, rather than number of responses,
      controlled choice responding. When the time between the first and last response
      was equated during both ratios, asymptotic accuracy was approximately equal to
      (two birds) or somewhat higher than (one bird) that obtained previously. The
      results of probes with intermediate fixed ratios and blackouts suggested that
      control of side-key choice had transferred from the time between the first and
      last response in ratios to blackout duration.

PMID- 16811820
TI  - Effects of reinforcement magnitude on interval and ratio schedules.
AB  - Rats' lever pressing was studied on three schedules of reinforcement: fixed
      interval, response-initiated fixed interval, and fixed ratio. In testing,
      concentration of the milk reinforcer was varied within each session. On all
      schedules, duration of the postreinforcement pause was an increasing function of
      the concentration of the preceding reinforcer. The running rate (response rate
      calculated by excluding the postreinforcement pauses) increased linearly as a
      function of the preceding magnitude of reinforcement on fixed interval, showed
      slight increases for two of the three animals on response-initiated fixed
      interval, and did not change systematically on fixed ratio. In all cases, the
      overall response rate either declined or showed no effect of concentration. The
      major effect of increasing the reinforcement magnitude was in determining the
      duration of the following postreinforcement pause, and changes in the response
      rate reflected this main effect.

PMID- 16811821
TI  - A shock-delivery system for newly hatched precocial birds.

PMID- 16811822
TI  - A digital sequential generator for implementing reinforcement schedules.

PMID- 16811823
TI  - Response-dependent shock in second-order fixed-ratio schedules of food
      presentation.
AB  - Three pigeons key pecked under second-order schedules in which the completion of
      two successive fixed-ratio 50 components constituted a reinforcement cycle.
      Tandem, chained, and brief-stimulus second-order schedules were studied when
      completion of the initial fixed-ratio 50 component delivered brief intense
      electric shock in every nth reinforcement cycle and n assumed values between one
      and nine. During sessions without shock, the brief-stimulus (unpaired with food)
      schedule generated higher rates of responding in the initial component than did
      the tandem schedule. Electric shock engendered increased time to the fifth
      response and a repeated pause-run pattern of not responding and responding,
      particuuarly in the initial component, even with shock scheduled in every ninth
      reinforcement cycle. The results were consistent with those reported for shock of
      a shorter duration scheduled in every reinforcement cycle. The overall rate of
      responding decreased as a function of increasing shock density and was lower in
      brief-stimulus than in tandem schedules.

PMID- 16811824
TI  - The discriminative control of free-operant avoidance despite exposure to shock
      during the stimulus correlated with nonreinforcement.
AB  - Four rats were trained in darkness on a free-operant avoidance procedure in which
      shocks occurred randomly, but lever presses could reduce their frequency.
      Discrimination training followed, during which responses in light continued to
      reduce shock frequency, but responses in darkness had no effect. During each
      cycle, the light period was 4 min, while darkness lasted only until a 20-sec
      interval had elapsed without a response. This no-response requirement was
      increased to 40 sec for three animals and eventually to 60 sec for two of them.
      Discriminative control developed, despite a greater shock density in the dark,
      with response rate and number of responses per shock maintained or increasing
      during light and decreasing to very low values in darkness. Two animals were
      later exposed to a procedure in which shock density was unaffected by responding
      either in light or darkness. A 60-sec no-response requirement was continued in
      the dark. Discriminative control persisted through 42 sessions for one animal and
      required 45 sessions to approach extinction for the other animal. The role of the
      light as a potential conditioned reinforcer of other behavior in the dark was
      implicated in the development and persistence of discriminative control. These
      data support shock-frequency reduction as reinforcement for avoidance behavior.

PMID- 16811825
TI  - The control of switching into blackout during extinction.
AB  - During the extinction component of a multiple variable-interval extinction
      schedule, four pigeons learned to peck a second key that switched off the
      keylights. Two experiments attempted to isolate the events that control this
      behavior. In the first experiment, switching into blackout was equally maintained
      when switches were restricted to the first minute as when they were restricted to
      the last minute of the extinction component. When switches could be emitted in
      the first and last minutes, they occurred more frequently in the first.
      Restricting switching to the first minute of each component and eliminating the
      blackout between components had no effect on switching. In the second experiment,
      when the stimulus correlated with extinction was omitted, switching decreased
      slightly. Omission of both multiple schedule stimuli decreased the switching
      rate, but switching was still maintained. Food reinforcement was then omitted and
      switching by two birds increased. Switching ceased when blackout was no longer
      the consequence of pecking the switching key. It was concluded that switching was
      not controlled by the similarity of the blackouts produced by the switching key
      and those that occurred between components; nor was it maintained by the temporal
      proximity of switching responses to the onset of the reinforced component.
      Finally, switching did not appear to be controlled by the main-key stimuli
      correlated with the components of the multiple schedule.

PMID- 16811826
TI  - Implications of the matching law for ratio responding.

PMID- 16811827
TI  - The role of the peck-food contingency on fixed-interval schedules.
AB  - Pigeons were trained to peck on a fixed-interval schedule of food reinforcement
      and then exposed to three schedules in which there was either no, or an indirect,
      relation between pecking and food delivery: (a) a conjunctive schedule in which
      food was delivered at fixed intervals, providing at least one peck was emitted in
      the interval; (b) a recycling version of the conjunctive schedule that
      essentially eliminated occasional peck-food contiguities (recycling conjunctive);
      (c) delivery of food at fixed intervals independently of the birds' behavior
      (fixed time). The rates and patterns of pecking sustained by these procedures
      depended on interfood interval and relative proximity of pecks to food.

PMID- 16811828
TI  - Discriminability of fixed-ratio schedules for pigeons: effects of absolute ratio
      size.
AB  - In a discrete-trial choice situation, 12 pigeons were trained to discriminate
      which of two different fixed ratios they had completed. Psychometric functions
      were obtained at three ratio requirements (i.e., with the larger ratio set at 10,
      20, or 30 responses) by gradually reducing the size of the smaller value.
      Although different response biases developed across subjects, in each case
      accuracy decreased systematically with ratio difference regardless of absolute
      ratio requirements. Above-chance performances were maintained even at relative
      ratio differences of 10% or less. Estimates of the Weber fraction showed that, in
      general, discriminability improved with absolute ratio size up to 30 responses,
      and beyond, when the results of other studies are considered. A similar trend
      held for rats studied by other investigators in fixed-ratio "counting" tasks at
      lower requirements. In terms of a signal-detection analysis, performance was
      similar to that reported for other species and dimensions. Taken together, the
      results suggest that for this somewhat novel dimension the same psychophysical
      relations hold as are commonly observed for exteroceptive stimuli.

PMID- 16811829
TI  - Reinforcement of behavioral patterns: shaping a scallop.
AB  - Temporal patterns of key pecking by pigeons were shaped by a schedule in which
      the delivery of food was contingent upon a measure of the overall extent to which
      the temporal pattern of behavior within a 5-sec trial conformed to a required
      pattern. This pattern approximated a constant rate of change in the rate of key
      pecking throughout the 5-sec trial. In comparison with behavior maintained by a
      classical fixed-interval 5-sec schedule, the new schedule controlled a better
      approximation to a "scallop" within individual trials and greatly reduced
      intersubject variability. These results are consistent with the view that the
      delivery of a reinforcer after a behavioral pattern a few seconds in duration may
      strengthen the entire pattern as a unit, or operant. The response topography
      contiguous with reinforcement may be a negligible fraction of the strengthened
      operant. One implication of this view is that mean response rate for such brief
      responses as key pecks and lever presses is a byproduct of whatever patterns are
      strengthened, and generally will not reveal fundamental controlling
      relationships, whenever a reinforcer is not contiguous with all the behavior on
      which it is contingent.

PMID- 16811830
TI  - The reinforcement value of schedule-induced drinking.
AB  - The effect of food reinforcement schedules on the reinforcement value of drinking
      water was evaluated. Food-deprived rats were exposed to concurrent, identical
      variable-time schedules of food presentation, the food thus being delivered
      independently of the rats' behavior. When the relative amount of time spent in a
      schedule component stabilized, an opportunity to drink water was introduced into
      one schedule component. The value of the variable-time schedules was varied from
      60 to 90 to 270 sec. The relative amount of time spent in the schedule component
      associated with drinking water was a decreasing function of food frequency for
      two animals and remained constant for the third. Drinking rates were direct
      functions of food frequency, and the amount of water drunk per pellet was an
      inverse function of food frequency. The reinforcement value of drinking water,
      according to the Matching Law, was a direct function of the frequency of food
      presentation. It was concluded that food reinforcement schedules indirectly
      influence rates of drinking by altering the reinforcement value of drinking water
      and that certain properties of schedule-induced drinking can be accounted for in
      terms of the reinforcement value of drinking water, the rate of drinking, and the
      frequency of food presentation.

PMID- 16811831
TI  - Time allocation in human vigilance.
AB  - Three human subjects detected unpredictable signals by pressing either of two
      telegraph keys. The relative frequencies with which detections occurred for the
      two alternatives were varied. The procedure included a changeover delay and
      response cost for letting go of a key. All subjects matched the relative time
      spent holding each key to the relative number of detections for that key, in
      conformity with the matching law. One subject's performance, which at first
      deviated from the relation, came into conformity with it when response cost was
      increased. Another subject's performance approximated matching more closely when
      the changeover delay was increased. The results confirm and extend the notions
      that choice consists in time allocation and that all behavior can be measured on
      the common scale of time.

PMID- 16811832
TI  - Economic and biological influences on a pigeon's key peck.
AB  - Pigeons were studied in a two-component multiple schedule. In the first phase of
      the experiment, key pecks were reinforced on a variable-interval 2-min schedule
      in both components and free food was delivered additionally during one component.
      When components alternated every 8 sec, all pigeons pecked at a much higher rate
      during the component with free food than during the other component. At a
      component duration of 16 min, the reverse was true: all pigeons pecked at a
      higher rate during the component without free food. In the second phase, the
      additional food during one component was made contingent on pecking. Responding
      during the component without the extra food remained essentially unchanged, as
      expected, since rate of reinforcement remained identical to that in the previous
      phase. However, rate of responding during the component with the extra food (now
      contingent on pecking) was elevated, compared to the rate in the first phase, and
      did not show the marked decline as component duration was increased.

PMID- 16811833
TI  - The measurement of sharing and cooperation as equity effects and some
      relationships between them.
AB  - The initial objective was to determine whether an increase in cooperative
      responses (minimal cooperation) was also accompanied by an increase in the degree
      of correspondence in the number of reinforcers of the two subjects (maximal
      cooperation). Correct matching-to-sample responses of seven pairs of male
      adolescents were reinforced with money. On each trial, a subject could (1) give
      the matching-to-sample problem to his coactor (give or cooperative responses), or
      (2) take the problem for himself (take responses). The first member of the pair
      to respond made the choice. Correspondence did increase under this procedure as
      compared to a baseline where problems were distributed randomly. However, the
      increased correspondence usually resulted from take responses rather than
      cooperative give responses. This equitable method of problem distribution,
      designated as sharing, was characterized by the subjects alternately taking
      problems. The spacing of daily sessions may have been partly responsible for the
      high degree of correspondence, because correspondence did not increase within the
      usual number of sessions when the sessions were massed, i.e., all in one day.
      Daily sessions require cooperative responses, i.e., each subject has to show up
      each day for the other to earn money, and this dependency upon the coactor's
      behavior may facilitate some sharing or cooperation to ensure the coactor's
      attendance.

PMID- 16811834
TI  - Ratio requirement and reinforcer effects in concurrent fixed-interval fixed-ratio
      schedules.
AB  - The fixed-ratio requirement was varied in concurrent fixed-interval fixed-ratio
      schedules. Fixed-interval responding was reinforced by food. In different phases,
      fixed-ratio responding was reinforced by food or water. There was a direct
      relation between the ratio requirement and interval response rates when both
      responses were reinforced with food, but essentially no relation when the
      reinforcers were different. The role of reinforcers in concurrent schedules
      merits detailed study.

PMID- 16811835
TI  - Compounding of discriminative stimuli correlated with chained and multiple
      schedules.
AB  - In studies of stimulus compounding (1) the stimuli are presented randomly, (2)
      primary reinforcement is correlated with each stimulus, (3) a specific response
      is emitted during each stimulus, and (4) the response is necessary to produce the
      reinforcer. The present experiments assessed the importance of these procedures
      by (1) presenting light and tone stimuli in fixed order, (2) removing
      reinforcement (food) during one stimulus, (3) preventing the response (lever
      pressing) from being emitted, and (4) eliminating the contingency between lever
      pressing and food. These variables were presented in various combinations within
      the context of chained and multiple schedules. When the stimuli were combined in
      the schedule component correlated with each stimulus, the frequency of lever
      pressing increased in most instances (additive summation). This suggests that the
      effect of combining stimuli was not closely tied to the specific procedures used
      in previous experiments. However, presenting the stimuli in a fixed order did
      have an effect: the level of responding to the compound was generally greatest
      when the stimuli were combined in the component correlated with the higher
      frequency of lever pressing to the single stimulus. Additive summation failed to
      occur consistently when response-independent food was correlated with each
      stimulus, and when both lever pressing and food were eliminated during one
      stimulus.

PMID- 16811836
TI  - Inhibitory control and errorless discrimination learning.
AB  - Pigeons learned to discriminate between a positive stimulus (white key) and a
      negative stimulus (red or green key, depending on the subject) via Terrace's
      fading procedure. Generalization tests, conducted with intermittent reinforcement
      for key pecking at various wavelengths, yielded minima at the value of the
      negative stimulus in most "errorless" birds. Terrace's contrary finding of flat
      gradients in errorless subjects probably resulted from a floor-effect (i.e.,
      virtually zero responding) produced by his extinction-test procedure. The present
      and other findings do not support Terrace's conclusions that the negative
      stimulus of an errorless discrimination is behaviorally neutral; inhibition
      apparently develops to the nonreinforced stimulus even during errorless
      discrimination learning. A negative correlation between stimulus and reinforcer
      seems the crucial factor in producing an inhibitory stimulus.

PMID- 16811837
TI  - Discriminative stimulus location as a determinant of positive and negative
      behavioral contrast in the pigeon.
AB  - Four pigeons were exposed to a series of two-component multiple schedules of
      reinforcement that ordinarily yield positive and negative behavioral contrast.
      The stimuli that signalled the component schedules were sometimes located on the
      response key and sometimes off. Positive behavioral contrast was observed only
      when the stimuli were on the key. Negative contrast was observed independent of
      stimulus location. These data suggest that positive and negative contrast may be
      causally unrelated, and support an account of contrast in terms of the summation
      of key pecks that are separately controlled by response-reinforcer and stimulus
      reinforcer dependencies.

PMID- 16811838
TI  - Response additivity: effects of superimposed free reinforcement on a variable
      interval baseline.
AB  - Three experiments examined the effects of superimposing free reinforcement (Free
      VI 30-sec) on behavior maintained by a response dependent mult VI 2-min VI 2-min
      schedule of reinforcement. Experiment I used pigeons as subjects, key pecking as
      the response, and colors of response key as the stimuli associated with the
      multiple-schedule components. When free reinforcement was added during only one
      component (Differential condition) a large and highly significant increase in
      response rate developed in this component. Adding free reinforcement during both
      components (Nondifferential condition) produced smaller and far less-consistent
      effects. An entirely different pattern of results was obtained in two subsequent
      experiments, where similar procedures and reinforcement conditions were used with
      rats as subjects and bar pressing as the response. In both Experiments II and
      III, response rates decreased to the stimulus associated with added free
      reinforcement in the Differential condition. These findings are interpreted as
      the result of interactions between behavior maintained by response-reinforcer
      contingencies and behavior maintained by stimulus-reinforcer contingencies. As
      such, they support the main assumption of an autoshaping theory of behavioral
      contrast, that additivity of responding generated by the two kinds of contingency
      can occur only in situations favorable to autoshaping.

PMID- 16811839
TI  - Matching and contrast on several concurrent treadle-press schedules.
AB  - Four White King pigeons pressed treadles for food reinforcement on several
      concurrent variable-interval variable-interval schedules. The rate of
      reinforcement available for responding in one of the two component schedules was
      held constant at 30 reinforcers per hour. The rate of reinforcement available for
      responding in the other was varied from 120 to 60 to 15, and then to 30
      reinforcers per hour. The relative rate of responding in each component schedule
      equalled the relative rate of reinforcement that the component provided. And,
      behavioral contrast, defined as an inverse relationship between the rate of
      responding in the constant component and the rate of reinforcement obtained by
      responding in the other component, occurred for all schedules.

PMID- 16811840
TI  - Key pecking in pigeons produced by pairing keylight with inaccessible grain.
AB  - In Experiment I, keylight was paired with inaccessible grain delivery (under two
      conditions of keylight intensity) to determine if autoshaping would occur in the
      absence of primary reinforcement. In Experiment II, the procedure was repeated
      with accessible grain, for comparison. In Experiment III, the procedures were
      repeated with explicitly unpaired presentations of keylight and either
      inaccessible or accessible grain. The results indicated that key pecking occurred
      as quickly in the presence of keylight pairings with inaccessible grain as with
      accessible grain, though (except for one bird) key pecking was not maintained
      with inaccessible grain. Furthermore, compared to the dim keylight, the bright
      keylight greatly suppressed key pecking when paired with inaccessible grain, and
      reduced the rate of key pecking when paired with accessible grain. Little key
      pecking occurred in groups exposed to explicitly unpaired presentations of
      keylight (whether bright or dim) and grain (whether accessible or inaccessible).
      When the birds in Experiment III were retested with explicitly paired
      presentations of keylight and grain, little key pecking was observed, suggesting
      suppressive effects of prior explicitly unpaired presentations. It is suggested
      that the effects of key-brightness manipulation were produced by the association
      of grain with cues other than the response key, or by distraction produced by
      partial illumination of the grain hopper.

PMID- 16811841
TI  - Generalization of excitation and inhibition after different amounts of training
      of an avoidance baseline.
AB  - After acquisition of a treadle-pressing response maintained by an avoidance
      contingency, four groups of pigeons received interdimensional discrimination
      training. For two groups, the positive stimulus was a 1000-Hertz tone correlated
      with the avoidance schedule and the negative stimulus was noise correlated with
      extinction. The discriminative stimuli were reversed for the other two groups.
      For two groups, the test stimuli were presented during extinction without any
      shocks during the test stimuli, for the other two groups, an unavoidable shock
      was presented during each test stimulus. Generalization was measured daily during
      discrimination training by randomly substituting each of six test frequencies for
      the 1000-Hertz tone. When the 1000-Hertz tone was correlated with the avoidance
      schedule, the number of responses to it increased and the excitatory gradient
      became steeper as a function of the amount of training. When the 1000-Hertz tone
      was associated with extinction, the number of responses to it decreased as a
      function of days of training and the inhibitory gradient became slightly steeper,
      provided that responding to the test stimulus was elevated by unavoidable shock.
      The training effects parallel those obtained with positive reinforcement.

PMID- 16811842
TI  - Stimulus control in a discrimination based on a distinctive feature.
AB  - Six pigeons were instrumentally trained to discriminate between two displays that
      differed only by the presence of a distinctive feature on the positive or food
      correlated display. In accordance with previous studies, subjects learned the
      discrimination and, in the presence of the positive display, directed most of
      their responses to the distinctive feature, although responses to the common
      feature were also reinforced. Subsequent generalization tests revealed that on
      the positive display, both common and distinctive features produced decremental
      gradients, contradicting Farthing's (1971) statement that the common feature
      acquires a control function opposite that of the distinctive feature. Procedural
      differences probably caused the discrepancy in results; within a display,
      Farthing presented common and distinctive features successively; the present
      study used simultaneous presentations of common and distinctive stimuli.

PMID- 16811843
TI  - Schedule-induced drinking as a function of percentage reinforcement.
AB  - Drinking was recorded in rats while lever pressing was maintained on a series of
      percentage reinforcement schedules in which the per cent of 1-min fixed intervals
      terminating with food was 100, 90, 30, 70, 10, 50, and 100%. Intervals in which a
      pellet was omitted were terminated by brief light flash and click stimuli that
      were also correlated with food presentations. Drinking failed to develop in five
      of six subjects following intervals in which the brief stimuli were presented
      regardless of percentage reinforcement. Postpellet drinking, which followed
      intervals terminated with pellet delivery, however, increased in both duration
      and amount ingested per interval as percentage reinforcement was systematically
      decreased. The increase in postpellet drinking above that produced by 100%
      reinforcement was interpreted as an analogue of the positive-contrast effect
      observed with food-reinforced operants.

PMID- 16811844
TI  - Eccentric stimuli on multiple fixed-interval schedules.
AB  - The effects of presenting a different ("eccentric") stimulus for one interval
      during either or both components of a cyclic multiple fixed-interval fixed
      interval schedule, with 12 short and four long intervals per cycle, were studied
      in three experiments. Eccentric stimuli in the short-interval component reliably
      produced a persistent, substantial elevation in key-peck rate. The effect appears
      to depend on schedule context and an initial "disinhibiting" effect of the
      eccentric stimulus.

PMID- 16811845
TI  - Reinforcement contingencies as discriminative stimuli.
AB  - A matching paradigm was used to examine the discriminative properties of two
      different reinforcement contingencies. Responding according to either a
      differential-reinforcement-of-low-rate or a differential-reinforcement-of-other
      behavior schedule produced a choice situation in which each of two keys was
      illuminated with a unique color. The correct choice response was defined by the
      contingency that was met to produce the choice. Eighty to 100% correct matching
      was obtained and recovered during two reversals of the choice stimuli.
      Introduction of a delay between completion of the reinforcement contingency and
      presentation of the choice stimuli resulted in decrements in matching
      performances similar to those obtained when other types of sample stimuli are
      used. The results provided evidence of the discriminative properties of the
      relation between behavior and other classes of stimuli.

PMID- 16811846
TI  - Concurrent assessment of schedule and intensity control across successive
      discriminations.
AB  - Two chinchillas were trained on a series of two-valued auditory intensity
      discriminations. Lever presses were reinforced when no tone was present and not
      reinforced in the presence of a four-kiloHertz tone. The intensity of the
      nonreinforced tone was successively decreased, increasing the difficulty of the
      discrimination, until differential responding resembled that on a mixed schedule
      (no-tone-no-tone). Response data were partitioned in such a way as to provide a
      continuing assessment of the relative amounts of control exerted by the
      reinforcement schedule and the sound intensity, respectively. Control by
      reinforcement density was a direct function of discrimination difficulty, whereas
      the control exerted by intensity was inversely related to difficulty. For these
      chinchillas, the absolute threshold value obtained at four kiloHertz was about
      two decibels referenced to 20 microNewtons per meter squared.

PMID- 16811847
TI  - The effect of the size of the test environment on behavior under two temporally
      defined schedules.
AB  - The effect of the size of the floor area of the operant test chamber on behavior
      was tested using a standard-size test chamber and a test chamber with one-fourth
      of the floor area of the standard chamber. Two groups of pigeons were tested
      under a differential-reinforcement-of-low-rate 15-sec schedule or a variable
      interval 60-sec schedule. Both groups of pigeons had higher response rates while
      in the smaller floor area. Pigeons under the differential-reinforcement-of-low
      rate schedule also showed a decrease in rate of reinforcement, an increase in
      ratio of responses to reinforcements, and an alteration in interresponse-time-per
      opportunity distributions when tested in the reduced floor-area condition. These
      effects are similar to those found under physical restraint, indicating that
      amount of floor space available for locomotion interacts with schedule behavior
      and that physical restraint may be regarded as the lower limiting value of amount
      of floor area available for locomotion.

PMID- 16811848
TI  - Local patterns of responding maintained by concurrent and multiple schedules.
AB  - Local patterns of responding were studied when pigeons pecked for food in
      concurrent variable-interval schedules (Experiment I) and in multiple variable
      interval schedules (Experiment II). In Experiment I, similarities in the
      distribution of interresponse times on the two keys provided further evidence
      that responding on concurrent schedules is determined more by allocation of time
      than by changes in local pattern of responding. Relative responding in local
      intervals since a preceding reinforcement showed consistent deviations from
      matching between relative responding and relative reinforcement in various
      postreinforcement intervals. Response rates in local intervals since a preceding
      changeover showed that rate of responding is not the same on both keys in all
      postchangeover intervals. The relative amount of time consumed by interchangeover
      times of a given duration approximately matched relative frequency of reinforced
      interchangeover times of that duration. However, computer simulation showed that
      this matching was probably a necessary artifact of concurrent schedules. In
      Experiment II, when component durations were 180 sec, the relationship between
      distribution of interresponse times and rate of reinforcement in the component
      showed that responding was determined by local pattern of responding in the
      components. Since responding on concurrent schedules appears to be determined by
      time allocation, this result would establish a behavioral difference between
      multiple and concurrent schedules. However, when component durations were 5 sec,
      local pattern of responding in a component (defined by interresponse times) was
      less important in determining responding than was amount of time spent responding
      in a component (defined by latencies). In fact, with 5-sec component durations,
      the relative amount of time spent responding in a component approximately matched
      relative frequency of reinforcement in the component. Thus, as component
      durations in multiple schedules decrease, multiple schedules become more like
      concurrent schedules, in the sense that responding is affected by allocation of
      time rather than by local pattern of responding.

PMID- 16811849
TI  - Choice and response contingencies.
AB  - Two experiments investigated the extent to which response contingencies influence
      the choice between two schedules of reinforcement by exposing pigeons to a
      concurrent-chains procedure in which reinforcers in one terminal link were
      response-independent, and in the other terminal link, response-dependent. In
      Experiment 1, the pigeons were indifferent between an aperiodic, response
      independent schedule and an aperiodic, response-dependent schedule that required
      a minimum rate of responding. This finding limits the generality of a required
      rate contingency as a determinant of choice, which contingency had been
      previously demonstrated in a context of periodic reinforcement to evoke
      preference for an alternate schedule. In Experiment 2, the pigeons preferred a
      periodic, response-independent schedule to a periodic, response-dependent
      schedule that shared a feature with a required-rate schedule: there was a
      requirement to respond early in the interreinforcement interval, when responding
      produced reinforcement only later. The results of the two experiments suggest the
      following general interpretation: pigeons prefer a second schedule to the extent
      that the response contingencies of the first schedule must be satisfied during
      discriminable periods of nonreinforcement.

PMID- 16811850
TI  - Choice for signalled over unsignalled shock as a function of shock intensity.
AB  - Choice between a signalled shock schedule and an unsignalled one was examined at
      various shock intensities. Three rats were given the opportunity to change from
      the unsignalled schedule to the signalled one at intensity values between 0.15 mA
      and 1.0 mA. Steps were usually 0.15 mA and both ascending and descending series
      were given. For two other rats, shock intensity increased from 0.20 mA to 1.0 mA
      in 0.20-mA increments; for two additional rats, shock intensity was first 3.0 mA
      and was then reduced to 1.0 mA. Subjects tended to remain in the unsignalled
      schedule at the lower shock intensities, but spent most of each session under the
      signalled schedule at the higher intensities (1.0 mA and 3.0 mA). In addition,
      the time spent in the signalled schedule tended to vary systematically with shock
      intensity over at least part of the range of intensity values. It was concluded
      that the relationship between shock intensity and choice behavior is similar to
      the relationship between intensity and behavior in procedures involving
      avoidance, escape, and punishment.

PMID- 16811851
TI  - Behavioral similarity as a reinforcer for preschool children.
AB  - Three experiments evaluated whether behavioral similarity provided by an adult
      could serve as a reinforcer for the modelling behavior of four preschoolers. In
      each experiment, sessions consisted of two kinds of trials: (1) experimenter
      modelled trials, when the child's imitation of modelled motor responses was
      reinforced with praise and tokens, and (2) child-modelled trials when
      experimenter imitation of child-modelled responses was contingent upon the
      child's modelling one of three alternative responses: operation of a ball, horn,
      or clicker. Experiment I showed that the children consistently modelled whichever
      responses the experimenter imitated. Experiment II determined whether that
      performance was due to differences in the amount of experimenter behavior
      following imitated versus nonimitated child models or to experimenter imitation.
      Neither reducing nor increasing the amount of experimenter behavior following the
      children's nonimitated models altered their modelling of imitated responses.
      Experiment III evaluated whether experimenter imitation of child models was a
      reinforcer because the child's imitative responses were reinforced on
      experimenter-modelled trials. In Experiment III, the children's nonimitation of
      experimenter-models was reinforced with praise and tokens on a schedule of
      differential reinforcement of other behavior, yet they continued to model
      experimenter-imitated responses on child-modelled trials. These results indicate
      behavioral similarity was reinforcing, though no conditioning history through
      which it acquired that function was demonstrated.

PMID- 16811852
TI  - The effects of varying the distribution of generalization stimuli within a
      constant range upon the bisection of a sound-intensity interval by rats.
AB  - Two male, albino rats were trained on a two-valued, self-paced, discrete-trials
      auditory discrimination. In the presence of a high-intensity stimulus (90
      decibels SPL, 4 kiloHertz), response A was reinforced; in the presence of a low
      intensity stimulus (50 decibels SPL, 4 kiloHertz), response B was reinforced.
      When discrimination performance was asymptotic, stimuli intermediate in intensity
      were presented with the training stimuli in a maintained generalization paradigm.
      Generalization gradients were derived from the relative frequencies of response A
      in the presence of each stimulus. A relative frequency of 0.50 was then
      determined and used as the bisection point of the intensity interval defined by
      the 90- and 50-decibel stimuli. The bisection point varied with the distribution
      of the stimuli presented in generalization. This effect was similar to context
      effects seen in human psychophysics.

PMID- 16811853
TI  - Positive and negative behavioral contrast in the rat.
AB  - Three groups of rats received either 8, 23, or 53 sessions of multiple variable
      interval variable-interval baseline training before being shifted to a multiple
      extinction variable-interval schedule. The rate of responding during the
      unaltered component was higher for the groups shifted to multiple extinction
      variable-interval than for control groups remaining on multiple variable-interval
      variable-interval (positive contrast). Furthermore, when the multiple variable
      interval variable-interval schedule was re-instated, stable negative contrast was
      found in the groups that had received 23 or 53 baseline sessions, but not for the
      group that had received only eight sessions. Positive and negative contrast were
      also demonstrated in the eight and 23-session groups when the multiple extinction
      variable-interval and multiple variable-interval variable-interval schedules were
      re-administered in further phases of the experiment. These results suggest that
      both positive and negative behavioral contrast can be obtained reliably in a
      species other than the pigeon.

PMID- 16811854
TI  - On the minimal conditions for the development of a peak-shift and inhibitory
      stimulus control.
AB  - Failures to obtain a peak-shift and inhibitory stimulus control following massed
      extinction in the presence of intra- and interdimensional stimuli confirm earlier
      results reported by Honig, Thomas, and Guttman (1959) and by Weisman and Palmer
      (1969). Peak-shifts and inhibitory stimulus control were observed when any of the
      following procedures intervened for 3 min between massed extinction and
      generalization testing: (1) S+ presented, responding reinforced; (2) S+
      presented, responding not reinforced; or, (3) noncontingent food presented in the
      presence of a dark key. Behavioral contrast was shown not to be a necessary
      antecedent for the occurrence of peak-shift or inhibitory stimulus control.

PMID- 16811855
TI  - Partial avoidance contingencies.
AB  - Rats were trained in a discrete-trial paradigm with no intertrial interval. The
      first response changed an auditory stimulus for the remainder of the trial.
      Shocks were delivered only at the end of the trial cycle. Avoidance contingencies
      were defined by the conditional probability of shock, given no response (P(0)),
      and the conditional probability of shock given a response (P(1)). The maximal
      avoidance contingency was P(0)=1.0, P(1)=0, and noncontingent conditions were
      those for which P(0)=P(1). In Experiment I, after training on the maximal
      contingency, three groups of subjects experienced either P(0)=P(1)=0,
      P(0)=P(1)=0.5, or P(0)=P(1)=1.0. Eight of 10 subjects stopped responding under
      the noncontingent conditions. Experiment II studied partial contingencies by
      varying P(0) and P(1). For one group, P(0) was reduced holding P(1)=0. Responding
      decreased to zero as P(0) approached zero. A second group was studied under
      P(1)>0, holding P(0)=1.0. For three of the six rats in this group, responding
      decreased to zero with increasing P(1). The other three maintained responding as
      P(1) was increased up to the noncontingent, P(1)=P(0)=1.0 value. The P(0) group
      was also studied with P(0)=P(1)>0, and half of these subjects responded. The
      results demonstrated two modes of response to weakening or eliminating the
      avoidance contingency. Some subjects were sensitive to contingency only, and
      insensitive to changes in shock density. Approximately one half of the subjects
      were sensitive to both contingency and shock density. This shared control was
      observed only when P(1)> 0.

PMID- 16811856
TI  - The effect of timeout on performance on a variable-interval schedule of electric
      shock presentation.
AB  - Responding was maintained in squirrel monkeys under variable-interval schedules
      of electric shock presentation when a period of timeout followed each response
      dependent shock. Response rate decreased when timeout duration was decreased, and
      responding ceased when timeout was eliminated. These results indicate that under
      certain conditions, a shock-free period following each response-produced shock is
      necessary to maintain responding.

PMID- 16811857
TI  - Unequal reinforcer magnitudes and relative preference for cooperation in the
      dyad.
AB  - College-student subjects, who were paired with a confederate, chose to respond
      either independently or cooperatively for money reinforcers. The subject's
      relative preference for cooperation was assessed by a procedure (analogous to the
      psychophysical method of limits) in which response choice was monitored as
      reinforcer magnitude for one response mode was systematically varied while the
      other remained constant. Relative preference for cooperation was assessed when
      the confederate's payoff for cooperation was greater than the subject's
      (Experiment I) and when the confederate's payoff for independent responding was
      less than the subject's (Experiment II). For some subjects, changes in the
      confederate's reinforcer magnitudes resulted in shifts in relative preference for
      cooperation, which reduced the earnings differences, even though these preference
      shifts reduced the subject's absolute earnings. For those subjects for whom
      within-dyad differences in reinforcer magnitude produced no effect, a changeover
      button was introduced that allowed the subject to eliminate the payoff difference
      without reducing her own earnings; some subjects used this changeover button to
      eliminate earnings differences. Thus, the behavior of subjects varied, in part,
      as a function of reinforcer magnitudes provided for the confederate.

PMID- 16811858
TI  - Maximizing and matching on concurrent ratio schedules.
AB  - Pigeons on concurrent variable-ratio variable-ratio schedules usually, though not
      always, maximize reinforcements per response. When the ratios are equal,
      maximization implies no particular distribution of responses to the two
      alternatives. When the ratios are unequal, maximization calls for exclusive
      preference for the smaller ratio. Responding conformed to these requirements for
      maximizing, which are further shown to be consistent with the conception of
      reinforcement implicit in the matching law governing relative responding in
      concurrent interval schedules.

PMID- 16811859
TI  - The shaping of phylogenic behavior.

PMID- 16811860
TI  - Conjunctive schedules of reinforcement II: response requirements and stimulus
      effects.
AB  - Responding of three pigeons was maintained under conjunctive fixed-ratio, fixed
      interval schedules where a key peck produced food after both schedule
      requirements were completed. The individual schedule requirements were then
      successively removed and reinstated with responding maintained under the
      following conditions: conjunctive fixed-ratio, fixed-time; fixed-time; and fixed
      interval schedules. Patterns of responding changed in accord with the successive
      removal of the schedule requirements. Compared to the conjunctive fixed-ratio,
      fixed-interval schedule, pause duration increased and response rate decreased
      under conjunctive fixed-ratio, fixed-time schedules and under fixed-time
      schedules alone. Overall mean rates of responding were highest and pause duration
      lowest under fixed-interval schedules. When changes in the keylight colors were
      correlated with completion of the fixed-ratio, the end of the fixed-interval, or
      both of these conditions, the pattern of responding was modified and indicated a
      greater degree of control by the individual schedules. Although two birds showed
      large increases in interreinforcement time when they were initially exposed to
      the conjunctive schedule, when responding stabilized this measure was largely
      invariant for all birds across most schedule conditions.

PMID- 16811861
TI  - Two-component schedules of differential-reinforcement-of-low-rate.
AB  - Two-component schedules of differential-reinforcement-of-low-rate were presented,
      where the contingencies specified separately two minimum interresponse times,
      t(1) and t(2), required for reinforcement, depending on whether the interresponse
      time was initiated by, in one case, a reinforced response (t(1)) or, in the
      other, a nonreinforced response (t(2)). A distinctive pattern of responding
      developed on each of the two contingencies. Duration of an interresponse time
      approximated t(1) when the t(1) contingency was in effect, and t(2) when the t(2)
      contingency was in effect. This relationship persisted even when t(2) was shorter
      than t(1), and responding at a higher rate on the t(1) contingency would have
      greatly increased the rate of reinforcement. Increasing the value of t(2)
      resulted in both longer interresponse times on the t(1) contingency, and a higher
      probability of a response-burst on those occasions when the contingency switched
      from t(1) to t(2). The results indicated that both reinforced and nonreinforced
      responses functioned as discriminative events in determining the duration of
      following interresponse times.

PMID- 16811862
TI  - Response-rate invariance in concurrent schedules: effects of different changeover
      contingencies.
AB  - In a two-key chamber, one key (the food key) was either red or green with
      different variable-interval schedules operating concurrently in each color and a
      second key (the changeover key) served to change the food-key color. Three
      pigeons were trained with either a 2-sec changeover delay or a 0-sec changeover
      delay and three birds with a fixed-ratio 2 on the changeover key instead of a
      changeover delay. The proportion of time spent in red approximated the proportion
      of reinforcers delivered in red for all birds. When the procedure was changed so
      that reinforcers were signalled in the green schedule, rates of reinforcement
      were unaltered, but the pigeons spent virtually the whole session in red.
      Changeovers to green were allowed only when a reinforcer was assigned by the
      schedule associated with green. For all pigeons with the fixed-ratio requirement
      on the changeover key or with a 0-sec changeover delay, the overall rate of red
      key responses was higher during the signalling condition than during unsignalled,
      or baseline, condition. The present data question the generality of previous
      reports that the rate of one response is independent of the amount of time
      allocated to the alternative response.

PMID- 16811863
TI  - Time allocation on concurrent schedules with asymmetrical response requirements.
AB  - Pigeons were trained on concurrent schedules in which key pecking was required by
      both schedules (concurrent variable-interval variable-interval schedules) and on
      concurrent schedules in which key pecking was required by only one of the
      schedules (concurrent variable-interval variable-time schedules). The
      distribution of reinforcements was systematically varied with both types of
      concurrent schedules. The distribution of time between the schedules depended on
      the reinforcement distribution and was independent of the symmetry of the
      response requirement. The relation between time and reinforcement distributions
      appears to be invariant over a wide range of manipulations of responding
      maintained by concurrent schedules.

PMID- 16811864
TI  - Some variables affecting rate of key pecking during response-independent
      procedures (autoshaping).
AB  - Rate of key pecking by pigeons subjected to response-independent procedures in
      which a stimulus on the response key preceded food presentation was investigated
      in eight experiments. Color and shape of the stimulus, duration of the stimulus,
      probability of food following the stimulus, duration of the intertrial interval,
      and duration of food presentation were varied separately and in combination. All
      variables studied, except color and shape of the stimulus, had a reliable effect
      on pecking rate, but some variables had stronger effects than others. Rapid key
      pecking may be obtained with a variety of response-independent procedures, as
      well as by response-dependent reinforcement. The results of experiments in which
      food is both dependent on key pecking and correlated with stimulus conditions are
      not representative of simple operant effects. Key pecking is an ideal response
      for studying the simultaneous operation of response-reinforcer and stimulus
      reinforcer effects.

PMID- 16811865
TI  - Preference and discrimination between response-dependent and response-independent
      schedules of reinforcement.
AB  - Four Asian quail (Coturnix coturnix japonica) were exposed to concurrent-chain
      schedules, the terminal links of which were either variable-interval 30 sec and
      variable-time 30 sec, or fixed-interval 30 sec and fixed-time 30 sec. Except for
      one bird that exhibited a preference for the variable-interval schedule over the
      variable-time schedule, no consistent preferences were demonstrated for response
      dependent or response-independent schedules. However, response rates were three
      times greater on response-dependent than on response-independent schedules. The
      discrimination between terminal-link schedules was rapidly recovered after the
      schedule positions were reversed. Casual observations revealed that the birds
      engaged in stereotypic circling and pecking while the response-independent
      schedules were operative.

PMID- 16811866
TI  - Freedom and knowledge: an experimental analysis of preference in pigeons.
AB  - Relative responding in initial links of concurrent-chain schedules showed that
      pigeons preferred free to forced choices and informative to uninformative
      stimuli. Variable-interval initial links on two lower keys (white) of a six-key
      chamber produced terminal links on either two upper-left keys (blue and/or amber)
      or two upper-right keys (green and/or red). Terminal.links in which pecks on
      either of two lit keys produced fixed-interval reinforcement (free choice) were
      preferred to links with only one lit fixed-interval key available (forced
      choice). Terminal links with different key colors correlated with concurrent
      fixed-interval reinforcement and extinction (informative stimuli) were preferred
      to links with these schedules operating on same-color keys (uninformative
      stimuli). Scheduling extinction for one of the two free-choice keys assessed
      preference for two lit keys over one lit key, but confounded number with whether
      stimuli were informative. Fixed-interval reinforcement for both keys in each
      terminal link, but with different-color keys in one link and same-color keys in
      the other, showed that preference for informative stimuli did not depend on
      stimulus variety. Preferences were independent of relative responses per
      reinforcement and other properties of terminal-link performance.

PMID- 16811867
TI  - Inhibitory stimulus control following errorless discrimination learning.
AB  - Three generalization procedures were used to investigate inhibitory stimulus
      control following discrimination learning with few errors. Three groups of
      pigeons acquired a discrimination between a green stimulus (the positive
      stimulus) and a vertical or horizontal line (the negative stimulus) through
      differential autoshaping followed by multiple schedule presentation of the two
      stimuli with gradually increasing stimulus durations. Genereralization testing
      was along a line-tilt continuum. For one group, the test involved a resistance-to
      reinforcement procedure in which responses to all line tilts were reinforced on a
      variable-interval schedule. For a second group, also tested with the resistance
      to-reinforcement procedure, the lines were superimposed on the green field that
      formerly served as the positive stimulus. A third group was tested in extinction
      with the combined stimuli. Control groups had no discrimination training but
      responding to green was nondifferentially reinforced. The control subjects
      responded more to all line tilts during testing than did the comparable
      experimental subjects, indicating that the negative stimulus had become an
      inhibitory stimulus. Both resistance-to-reinforcement groups revealed inhibitory
      gradients around the negative stimulus, but the gradient for the extinction group
      was relatively flat. These data are consistent with others that modify Terrace's
      early conclusion concerning the failure of inhibition to develop during errorless
      training.

PMID- 16811868
TI  - Second-order schedules: discrimination of components.
AB  - Pigeons were exposed to a series of second-order schedules in which the
      completion of a fixed number of fixed-interval components produced food. In
      Experiment 1, brief (2 sec) stimulus presentations occurred as each fixed
      interval component was completed. During the brief-stimulus presentation
      terminating the last fixed-interval component, a response was required on a
      second key, the brief-stimulus key, to produce food. Responses on the brief
      stimulus key before the last brief-stimulus presentation had no scheduled
      consequences, but served as a measure of the extent to which the final component
      was discriminated from preceding components. Whether there were one, two, four,
      or eight fixed-interval components, responses on the brief-stimulus key occurred
      during virtually every brief-stimulus presentation. In Experiment 2, an attempt
      was made to punish unnecessary responses on the brief-stimulus key, i.e.,
      responses on the brief-stimulus key that occurred before the last component. None
      of the pigeons learned to withhold these responses, even though they produced a
      15-sec timeout and loss of primary reinforcement. In Experiment 3, different key
      colors were associated with each component of a second-order schedule (a chain
      schedule). In contrast to Experiment 1, brief-stimulus key responses were
      confined to the last component. It was concluded that pigeons do not discriminate
      well between components of second-order schedules unless a unique exteroceptive
      cue is provided for each component. The relative discriminability of the
      components may account for the observed differences in initial-component response
      rates between comparable brief-stimulus, tandem, and chain schedules.

PMID- 16811869
TI  - Second-order schedules of token reinforcement: effects of varying the schedule of
      food presentation.
AB  - In the initial link of a complex schedule, one discriminative stimulus was
      presented and lever pressing produced tokens on fixed-ratio schedules. In the
      terminal link, signalled by a second discriminative stimulus, deposits of the
      tokens produced food. With two rats, the terminal link was presented after each
      sixth component schedule of token reinforcement was completed. With the other two
      rats, the terminal link was presented following the first component schedule
      completed after a fixed interval. During the terminal link, each token deposit
      initially produced food. The schedule of food presentation was subsequently
      increased such that an increasing number of token deposits in the terminal link
      was required for each food presentation. Rates of lever pressing in the initial
      link were inversely related to the schedule of food presentation in the terminal
      link. These results are similar to those of experiments that have varied
      schedules of food presentation in chained schedules. Rates and patterns of
      responding controlled throughout the initial link were more similar to those
      ordinarily controlled by second-order brief-stimulus schedules than to those
      controlled by comparable extended chained schedules.

PMID- 16811870
TI  - Short-component multiple schedules: effects of relative reinforcement duration.
AB  - Pigeons were exposed to multiple variable-interval 2-min variable-interval 2-min
      schedules of food presentation in which relative duration of food presentation
      was manipulated. When components alternated every 5 sec and were scheduled on
      separate response keys, relative response rates closely matched relative
      reinforcement duration in three of four pigeons. On the other hand, relative
      response rates were insensitive to relative reinforcement duration when
      components scheduled on a single response key alternated every 5 sec, and when
      components scheduled on separate response keys alternated every 2 min. Thus, both
      rapid alternation and spatial separation of components were necessary to produce
      approximate matching of relative responding to relative reinforcement duration.
      This finding contrasts with previous findings that only rapid component
      alternation is necessary for matching when relative rate of reinforcement is
      manipulated.

PMID- 16811871
TI  - Performance in concurrent interval schedules: a systematic replication.
AB  - Five pigeons were trained on a variety of concurrent interval schedules that
      arranged reinforcements at either fixed or variable times after the last
      reinforcement. Two measures were obtained: the number of responses on each
      schedule, and the time spent responding on each schedule. Ratios of response
      rates on the two schedules did not equal ratios of reinforcement rates when both
      schedules were variable nor when one was variable and the other fixed. Ratios of
      times spent responding approximately equalled ratios of reinforcement rates when
      both schedules were variable, but did not do so when one was fixed.

PMID- 16811872
TI  - Behavioral contrast in the pigeon: a study of the duration of key pecking
      maintained on multiple schedules of reinforcement.
AB  - Pecks on an operant key were reinforced on either multiple variable-interval
      variable-interval or multiple variable-interval extinction schedules of
      reinforcement. The stimuli that signalled the multiple-schedule components were
      located on a second key (signal key), and a changeover delay prevented
      reinforcement of signal key-peck-operant key-peck sequences. No behavioral
      contrast was observed on the operant key, and appreciable responding to the
      signal key occurred during the variable-interval component of the multiple
      variable-interval extinction procedure. Peck durations on the signal key were
      markedly shorter than peck durations on the operant key. Moreover, most responses
      on the signal key occurred just after the multiple-schedule components changed.
      These data support an account of behavioral contrast in terms of the summation of
      pecks that are separately controlled by stimulus-reinforcer and response
      reinforcer dependencies, and suggest that the stimulus-reinforcer dependency is
      responsible primarily for local contrast. In addition, the data suggest that
      pecks that are controlled by these two dependencies may belong to topographically
      different classes.

PMID- 16811873
TI  - Maintenance of behavior controlling the duration of discriminative stimuli.
AB  - THE MAINTENANCE OF A RESPONSE CONTROLLING THE DURATION OF POSITIVE AND NEGATIVE
      DISCRIMINATIVE STIMULI IN A MULTIPLE SCHEDULE WAS EXAMINED WITH RESPECT TO THE
      POSSIBLE CONSEQUENCES OF THE RESPONSE: none, escape from the negative stimulus,
      production of the positive stimulus, and initiation of the reinforcement schedule
      associated with the latter. The last two seemed to be the major factors in
      producing and maintaining the response. Escape from the negative stimulus
      maintained it in most subjects, but only at a much lower level.

PMID- 16811874
TI  - The blocking of reinforcement control.
AB  - Two experiments were conducted to extend the blocking effect to the reinforcement
      of a response. A delayed reinforcement contingency was presented to subjects with
      or without a previously pretrained response available during the delay interval.
      The interpolated response had no scheduled effect on delivery of the reinforcer,
      but its availability reduced strengthening of the initial response, which
      completely extinguished for some subjects. The results were interpreted as
      support for blocking as a fundamental principle of behavior, and as evidence
      against the principle of reinforcement being stated solely in terms of temporal
      proximity between response and reinforcer.

PMID- 16811875
TI  - Rapid acquisition of discrete-trial lever-press avoidance: effects of signal
      shock interval.
AB  - Acquisition of discrete-trial lever-press avoidance learning was studied in three
      experiments. Experiment I compared a new training procedure, which produces rates
      of lever-press avoidance learning comparable to those obtained in shuttle boxes,
      with a "conventional", less efficient training procedure. A factorial design was
      used to compare continuous versus intermittent shock and a long-variable versus a
      short-fixed signal-shock interval. Learning was best in the groups trained with
      the long and variable interval and poorest in those trained with the short and
      fixed interval. Type of shock had no effect. Experiment II separated the effects
      of duration from those of variability of the signal-shock interval. Fixed and
      variable intervals of 10 and 60 sec were tested and duration was the only
      significant factor. Experiment III addressed the effect of the differential
      opportunity to avoid provided by long signal-shock intervals by varying this
      interval from 10 to 60 sec in 10-sec steps. Only the 10-sec group showed slow
      acquisition relative to the others. Analysis of avoidance response latencies
      showed that the distributions for all groups were positively skewed and that
      skewness increased with increasing duration of the signal-shock interval. At
      intervals longer than 20 sec, the animals made progressively less use of their
      increased opportunity to respond. The data do not support the opportunity-to
      respond interpretation of the effects of duration of signal-shock interval and
      suggest that some type of inhibitory process may block lever-press avoidance
      learning at intervals as short as 10 sec. The significance of these findings for
      species-specific defense reaction and preparedness theories was emphasized.

PMID- 16811876
TI  - A method for the objective study of tool-using behavior.
AB  - Key pecking for food was shaped in four crows within a conventional operant
      conditioning test chamber. When pecking stabilized, a metal screen with openings
      2.5 cm high by 1.0 cm wide, was placed over the response key, so that the crow
      could still see but could no longer peck the key. At the same time, several dozen
      wooden matchsticks, which could be used to operate the key, were placed in the
      test chamber. The crows made no use of these during 50 to 75 hr of exposure to
      this condition. Subsequently, the behavior of two crows was shaped so that they
      approached the matchsticks, picked one up in their beaks, approached the response
      key with the matchstick in their beak, and finally operated the response key by
      poking the matchstick through the screen. This shaping procedure was ineffective
      with the two other crows. However, these birds were successfully trained through
      positional fading of the tool. This involved suspending a metal rod from the
      ceiling so that it hung directly in front of the response key, and the crow had
      only to peck it to operate the key. Then, the rod was gradually lowered by
      lengthening its tether until it eventually rested on the floor of the test
      chamber. The principal advantage of this methodology is the automatic recording
      of the terminal (tool-using) behavior under study.

PMID- 16811877
TI  - Persistence of acquired behavioral control in the context of imprinting.
AB  - Newly hatched Khaki Campbell ducklings (Anas platyrhynchos domesticus) were
      exposed to a moving object that immediately suppressed distress vocalizations
      occurring in a novel environment. The static visual and auditory features of this
      object acquired the ability to suppress distress vocalizations after eight 20-min
      sessions of exposure to the object in motion. The acquired suppressive properties
      of these features were found to persist throughout thirty 20-min sessions given
      over 10 days. During these sessions, the ducklings were continually exposed to
      the static features in the absence of visual movement. In a second experiment,
      the ability of these features in the absence of visual movement. In a second
      experiment, the ability of these features to serve as reinforcement for a pecking
      response was shown to persist for up to 56 hr. In one duckling, presentations of
      the static visual features did not maintain pecking behavior. However, it was
      shown that pecking responses could be re-instated in this duckling by introducing
      novel stimuli to the environment.

PMID- 16811878
TI  - Behavioral contrast in rats with different reinforcers and different response
      topographies.
AB  - Experiment I demonstrated positive behavioral contrast in rats when one of two
      qualitatively different reinforcers (milk and pellets) was removed from a
      component of a multiple schedule. The contrast effect was larger and more
      enduring when milk was removed. Experiment II showed that the rats spent more
      time on the side of a shuttle-box on which milk was freely available than on the
      side on which pellets were freely available. Experiment III, a partial
      replication of Experiment I, failed to demonstrate the contrast effect of
      Experiment I. Experiment IV demonstrated contrast when two topographically
      distinct responses, nose-key poking and lever pressing, were required in
      different components of a multiple schedule. These results extend the conditions
      that generate behavioral contrast in rats.

PMID- 16811879
TI  - Stimulus-specific contrast effects during operant discrimination learning.
AB  - In two experiments, pigeons' responding was equally reinforced in the presence of
      four line-orientation stimuli. Responding was then reinforced when only two of
      the four orientation stimuli were present; the remaining two orientations
      appeared during extinction. Response rates were often highest in the stimulus
      adjacent to the orientations presented during extinction and often lowest in that
      orientation adjacent to the orientations presented with reinforcement. These
      effects were stronger and more persistent when the stimuli were separated by a
      smaller angle, rendering the discrimination more difficult. These and other data
      suggest that discrimination training may not be accurately explained in terms of
      the simple effects of reinforcement and nonreinforcement associated with isolated
      stimuli, nor by accounts that depend upon stimulus generalization. Recent
      accounts of contrast that depend upon "emotionality" produced by nonreinforced
      responding or upon reinforcement-elicited responses are also difficult to apply
      to these data.

PMID- 16811880
TI  - A re-examination of local contrast in multiple schedules.
AB  - Pigeons were presented with multiple schedules of alternating 90-sec components.
      When components in which grain was never presented alternated with components in
      which grain was presented on a variable-interval schedule, the average rate of
      responding in the variable-interval components increased, showing overall
      positive behavioral contrast. Unlike previous reports, this study found that the
      response rates for all birds increased toward the end of the variable-interval
      components as training proceeded. This increase in local response rate
      disappeared when the multiple schedule was composed solely of variable-interval
      components and reappeared when the variable-interval components were again
      alternated with extinction. This finding cannot be predicted or explained by
      recent theories of behavioral contrast based on autoshaping, and thus questions
      their sufficiency. We suggest that this local response-rate increase results from
      the predictable change from high to low density of reinforcement at the end of
      the fixed-duration component. Thus, the present effect apparently illustrates a
      different type of interaction between components of a multiple schedule than that
      described by previous theories of contrast. In a given procedure, either or both
      types of interaction may occur; neither provides a complete account of behavioral
      contrast.

PMID- 16811881
TI  - Peak shift following simultaneous discriminations.
AB  - Pigeons were exposed to stimuli presented on two keys. For some birds, the
      stimuli varied in a dimension of visual flicker-rate, and for others they varied
      in visual intensity. During differential training, concurrent schedules operated,
      with one stimulus correlated with one schedule and another stimulus correlated
      with a second schedule that arranged a lower, or zero, rate of reinforcement. The
      stimuli were alternated randomly on the two keys. Generalization tests were given
      in which the original two, and seven other stimuli lying in the same dimension,
      were presented in pairs on the two keys in various combinations. In the
      generalization test given after differential training, each bird showed peak
      shift. The data did not support explanation for peak shift that gave critical
      emphasis to whether stimuli were presented simultaneously or successively during
      differential training.

PMID- 16811882
TI  - Enhancement of conditioned reinforcement by uncertainty.
AB  - Pigeons were trained in three conditions. In the baseline condition, the birds
      responded on a fixed-interval schedule with the response key white. When the
      interval was completed, the key turned either red or green for a delay interval
      that was terminated by a grain presentation dependent on no key pecks during the
      final 2 sec. In the uncertainty condition, no grain was presented at the end of
      the delay periods when the key was red. In the certainty condition, the white
      light appeared only on occasions when pecking would turn the key green and
      produce food. Otherwise, the key was illuminated red throughout the total time
      period. The highest response rate in white occurred in the uncertainty condition,
      the next highest in the certainty condition, and the lowest in baseline. The
      results suggest that uncertainty facilitated responding, although uncertainty is
      not a necessary condition for conditioned reinforcement.

PMID- 16811883
TI  - Molecular contingencies: reinforcement probability.
AB  - Pigeons obtained food by responding in a discrete-trials two-choice probability
      learning experiment involving temporal stimuli. A given response alternative, a
      left- or right-key peck, had 11 associated reinforcement probabilities within
      each session. Reinforcement probability for a choice was an increasing or a
      decreasing function of the time interval immediately preceding the choice. The 11
      equiprobable temporal stimuli ranged from 1 to 11 sec in 1-sec classes.
      Preference tended to deviate from probability matching in the direction of
      maximizing; i.e., the percentage of choices of the preferred response alternative
      tended to exceed the probability of reinforcement for that alternative. This
      result was qualitatively consistent with probability-learning experiments using
      visual stimuli. The result is consistent with a molecular analysis of operant
      behavior and poses a difficulty for molar theories holding that local variations
      in reinforcement probability may safely be disregarded in the analysis of
      behavior maintained by operant paradigms.

PMID- 16811884
TI  - Response-shock delay as a reinforcer in avoidance behavior.
AB  - After rats received preliminary training to avoid shock on a discrete-trial
      retractable-bar avoidance procedure, the procedure was changed such that
      responses retracted the lever but did not affect the rate of shock. Responses
      only delayed the onset of shock. About half of the animals under these procedures
      responded consistently on almost 100% of the discrete-trial cycles over days.
      When short latencies maximized the response-shock delay, animals tended to make
      short-latency responses. When long latencies maximized the response-shock delay,
      animals tended to make long-latency responses. When all response latencies
      produced the same response-shock delay, animals made differing average-latency
      responses. And, when responses did not delay shock, most of the animals primarily
      engaged in shock-elicited responding while the other animals engaged in preshock
      responding.

PMID- 16811885
TI  - Concurrent second-order schedules of reinforcement.
AB  - Responses on one key (the main key) of a two-key chamber produced food according
      to a second-order variable-interval schedule with fixed-interval schedule
      components. A response on a second key (the changeover key) alternated colors on
      the main key and provided a second independent second-order variable-interval
      schedule with fixed-interval components. The fixed-interval component on one
      variable-interval schedule was held constant at 8 sec, while the fixed interval
      on the other variable-interval schedule was varied from 0 to 32 sec. Under some
      conditions, a brief stimulus terminated each fixed interval and generated fixed
      interval patterns; in other conditions, the brief stimulus was omitted. Relative
      response rate and relative time deviated substantially from scheduled relative
      reinforcement rate and, to a lesser extent, from obtained relative reinforcement
      rate under both brief-stimulus and no-stimulus conditions. Matching was observed
      with equal components on both schedules; with unequal components, increasingly
      greater proportions of time and responses than the matching relation would
      predict were spent on the variable-interval schedule containing the shorter
      component. Preference for the shorter fixed interval was typically more extreme
      under brief-stimulus than under no-stimulus schedules. The results limit the
      extension of the matching relation typically observed under simple concurrent
      variable-interval schedules to concurrent second-order variable-interval
      schedules.

PMID- 16811886
TI  - Switching from competition to sharing or cooperation at large response
      requirements: competition requires more responding.
AB  - Two pairs of high-school students matched-to-sample for money. On each trial, a
      subject could either respond on one lever to take the matching-to-sample problem
      himself (taking response) or respond on a second lever to give the problem to his
      coactor (giving response). The first subject to complete the response requirement
      determined the distribution of the problem. Competition maximizes the amount of
      responding over trials, i.e., both subjects make taking responses on each trial.
      Sharing and cooperation minimize responding: only one subject makes a taking
      response (sharing) or a giving response (cooperation) on each trial, and the
      subjects alternate responding such that there is an equitable distribution of
      responses and reinforcers over trials. Large increases in the fixed-ratio
      response requirement to distribute problems produced: (1) a switch from
      competition to sharing or cooperation, (2) the expected concomitant change from
      inequitable to equitable distributions of reinforcers, and (3) a reduction in the
      amount of responding for three of the four subjects. Previous animal research has
      shown that large response requirements may have aversive properties. Switching
      from competition to sharing or cooperation at large response requirements allows
      a reduction in responding and, at the same time, a moderate number of reinforcers
      for each subject.

PMID- 16811887
TI  - Stimulus properties of fixed-interval responses.
AB  - Responses in the first component of a chained schedule produced a change to the
      terminal component according to a fixed-interval schedule. The number of
      responses emitted in the fixed interval determined whether a variable-interval
      schedule of food presentation or extinction prevailed in the terminal component.
      In one condition, the variable-interval schedule was in effect only if the number
      of responses during the fixed interval was less than that specified; in another
      condition, the number of responses had to exceed that specified. The number of
      responses emitted in the fixed interval did not shift markedly in the direction
      required for food presentation. Instead, responding often tended to change in the
      opposite direction. Such an effect indicated that differential food presentation
      did not modify the reference behavior in accord with the requirement, but it was
      consistent with other data on fixed-interval schedule performance. Behavior in
      the terminal component, however, did reveal sensitivity to the relation between
      total responses emitted in the fixed interval and the availability of food.
      Response rate in the terminal component was a function of the proximity of the
      response number emitted in the fixed interval to that required for food
      presentation. Thus, response number served as a discriminative stimulus
      controlling subsequent performance.

PMID- 16811888
TI  - Response preferences of monkeys (Macaca mulatta) within wavelength and line-tilt
      dimensions.
AB  - Four rhesus monkeys were tested for preferences within the wavelength and line
      tilt dimensions. In the case of wavelength, the response panel was back
      illuminated by light of one of the following wavelengths, presented in a random
      manner: 470, 525, 580, and 635 nm. Similarly, the line-tilt dimension was
      studied, by presenting a 5 cm by 0.3 cm black bar tilted at 0, 30, 60, or 90
      degrees. No preferences were found within this latter dimension; in contrast,
      marked wavelength preferences existed, the order of preference being 470 (most
      preferred), 525, 580, and 635 nm (least preferred). These response preferences
      were resistant to behavioral manipulation; the number of responses to blue and to
      red in extinction was about equal when red was used as the training stimulus, but
      vastly different following training on blue. These results indicate that such
      response preferences must be taken into account in the design of a wide variety
      of experiments.

PMID- 16811889
TI  - The compleat associationist: a review of N. J. Mackintosh's The Psychology of
      Animal Learning.

PMID- 16811890
TI  - The schemapiric view. Notes on S. S. Stevens' philosophy and Psychophysics.

PMID- 16811891
TI  - Discriminative properties of briefly presented stimuli.
AB  - In Experiment I, pigeons' responses produced food according to a fixed-interval
      schedule while responses on the key also produced brief stimuli according to a
      variable-interval schedule. Each brief stimulus reset the fixed interval. Thus, a
      brief stimulus occurred irregularly but a fixed minimum time separated the
      occurrence of food from a brief stimulus. Pauses followed brief stimuli and were
      followed by an accelerated response rate until another brief stimulus or food
      occurred. In Experiment II, four control procedures were examined. (1) Brief
      stimulus presentations were omitted, producing a loss of response patterning. (2)
      A second-order schedule was studied with fixed-interval components. This schedule
      produced patterning following brief stimuli similar in kind and degree to that
      found in Experiment I. (3) A conjoint schedule was arranged in which food was no
      longer separated from the stimulus by a fixed time; pauses following the stimulus
      no longer resulted. (4) A brief food reinforcer replaced the brief visual
      stimulus, resulting in a constant response rate with no pausing following the
      brief food stimulus. The results suggest that the brief-stimulus effects were due
      to discriminative functions produced by the fixed temporal relation separating
      the stimulus from food.

PMID- 16811892
TI  - Procedural antecedents of behavioral contrast: a re-examination of errorless
      learning.
AB  - Behavioral contrast reliably occurred in pigeons following errorless
      discrimination training, contrary to Terrace's (1963) observations. In the main
      experiment, a 60-sec green keylight, associated with a variable-interval 30-sec
      schedule of reinforcement alternated with a 60-sec period of extinction when the
      key was dark. Such aspects of the discrimination training procedure as: (1) the
      amount of prior nondifferential exposure to the positive stimulus before the
      discrimination was instituted, and (2) the rapidity with which the negative
      stimulus was introduced (whether progressively or abruptly) directly influenced
      the amount of behavioral contrast produced. This occurred independently of the
      number of errors made by a pigeon during acquisition of the discrimination. In a
      series of control experiments, substitution of a red keylight for the dark key
      during extinction resulted in greater behavioral contrast, while an increase to 3
      min in the duration of the green keylight associated with reinforcement
      attenuated the behavioral contrast effect.

PMID- 16811893
TI  - Negative reinforcement with shock-frequency increase.
AB  - Two avoidance-conditioning experiments in which responding delayed shocks are
      reported. Rats receiving an average of two shocks per minute (imposed condition)
      could produce, by pressing a bar, a 3-min alternate condition. Six (Experiment I)
      or more (Experiment II) shocks occurred in the alternate condition. All shocks in
      the alternate condition were delayed and delivered at 1-sec intervals. With long
      delays, all subjects produced the alternate condition and spent a large
      percentage of each session in the alternate condition. The first experiment
      demonstrated that the longer the delay from onset of the alternate condition to
      onset of the shocks, the more session time spent in the alternate condition. The
      second experiment indicated that despite increased shock frequency, behavior is
      acquired and maintained when responding leads to sufficient delay. Individual
      subjects produced the alternate condition by bar pressing in essentially one of
      two patterns. One pattern, termed postshock, involved bar pressing immediately
      after shock; the other, termed posttransition, involved responding immediately
      after the transition from the alternate to the imposed condition. These results
      indicate that shock-frequency reduction is not necessary for avoidance
      conditioning; delay to shock onset is sufficient.

PMID- 16811894
TI  - Titration of schedule parameters by pigeons.
AB  - Pigeons were tested in a computer-controlled two-key chamber. A standard
      (nonchanging) schedule of reinforcement was in force on one key, and an adjusting
      schedule on the other. The schedules were available concurrently after each
      reinforcement, but after the first peck on either key (the choice peck), the
      schedule on the other key was made inoperative. The parameter of the adjusting
      schedule was decreased when the standard schedule was chosen and increased when
      the adjusting schedule was chosen. The standard schedule was changed only between
      sessions. Fixed intervals and fixed ratios were used as standard schedules, and
      intervals and ratios were used as adjusting schedules. When standard and
      adjusting schedules were of the same type, median parameters on the adjusting key
      equalled those of the standard schedules, at four values of each standard
      schedule. For four of five birds, and for the group median, similar curves could
      be plotted through the indifference points obtained from a standard ratio with an
      adjusting interval, and from a standard interval with an adjusting ratio. These
      points showed consistent individual differences, but they could be predicted by
      assuming that the median time from the choice peck to reinforcement should be the
      same on both keys. This is equivalent to treating the schedule as a concurrent
      chain and assuming that Herrnstein's quantitative law of effect applies.

PMID- 16811895
TI  - Short-term memory in the pigeon: relative recency.
AB  - Three pigeons pecked for food in an experiment in which each trial consisted of
      two phases. The first phase consisted of a pattern of three successively
      illuminated, randomly selected left or right keys. A subject was required to peck
      each of the lighted keys as they appeared. Thus, in the first phase, a subject
      emitted a pattern of three left- or right-key pecks. Over trials, all eight
      possible patterns appeared. A time interval separated the first phase from the
      second phase, which began with presentation of a randomly selected one of three
      cues. A reinforcer was delivered in the second phase if a subject pecked the side
      key that had appeared in the first phase in an ordinal position corresponding to
      the cue presented in the second phase. That is, the three cues probed a pigeon's
      memory for the side key it had pecked first, second, or third, in the first phase
      of a trial. The results show that a pigeon can remember for more than 4 sec the
      order in which it has just seen and pecked two lighted keys: a pigeon can
      remember the temporal organization or pattern of events in its recent
      environment. Consequently, the functional stimulus present when a reinforcer is
      delivered may include a subject's short-term memory for the temporal organization
      of recent events, such as the pattern of its own recent behavior. This
      possibility is consistent with a molecular analysis of operant behavior focusing
      on local patterns of behavior.

PMID- 16811896
TI  - Relation between level of food deprivation and rate of schedule-induced attack.
AB  - The relation between food deprivation and schedule-induced attack was
      investigated in four White Carneaux pigeons. Attack toward a mirror target was
      induced by a schedule of reinforcement in which 3-sec food presentations occurred
      at alternate intervals of 15 and 120 sec (multiple fixed-time 15-sec fixed-time
      120-sec schedule). A continuous tone was presented during the 15-sec periods; it
      was absent during the 120-sec periods. Each pigeon was tested at 65, 80, and 95%
      of its free-feeding weight in ascending, descending, and ascending orders,
      respectively. Two relations were apparent; an inverse relation between body
      weight and rate of attack, and a tendency for rate of attack to increase during
      the experiment. Reduction or elimination of attack when the mirror was covered
      with brown paper for some sessions indicated that the results were due neither to
      changes in activity that might covary with weight nor to habituation to the
      experimental situation.

PMID- 16811897
TI  - Matching with a trio of concurrent variable-interval schedules of reinforcement.
AB  - A trio of concurrent variable-interval schedules of reinforcement was arranged
      according to a changeover-key procedure, including a changeover delay of 1.5 sec.
      The three schedules provided a combined maximum reinforcement rate of 45
      reinforcements per hour. With that restriction, the nine experimental conditions
      included several combinations of variable-interval schedules, sometimes including
      extinction. The pigeons matched relative response rate and relative time to
      relative reinforcement rate. Relative time appeared to match some-what better
      than relative response rate. Performance adjusted rapidly from one experimental
      condition to the next, whether the change involved two or all three schedules of
      the concurrent trio.

PMID- 16811898
TI  - Choice and the rate of punishment in concurrent schedules.
AB  - Rats' responses on two levers were reinforced according to independent random
      interval 1.5-min food schedules. In addition, both lever presses were
      intermittently punished according to several concurrent random-interval random
      interval shock schedules. For the left, the scheduled rate of punishment was kept
      constant according to a random-interval 6-min schedule. For the right, the rate
      of punishment varied. As the frequency of punishment for the right lever press
      increased, its rate decreased. The rate of the left punished lever press
      increased, however, even though its scheduled reinforcement rate and punishment
      rate remained unchanged.

PMID- 16811899
TI  - Conjunctive schedules of reinforcement: III. A fixed-interval adjusting fixed
      ratio schedule.
AB  - Key pecking of three pigeons was studied under a conjunctive schedule that
      specified both a fixed-interval and an adjusting fixed-ratio requirement. The
      fixed-interval schedule was 6 min for one pigeon and 3 min for the other two. The
      size of the ratio requirement was determined within each cycle of the fixed
      interval by the duration of the pause before responding began. The fixed-ratio
      value was at maximum at the start of each fixed interval and decreased linearly
      until the first response occurred (adjusting fixed-ratio schedule). A peck
      produced food when the number of responses remaining on the fixed-ratio schedule
      was completed and when the fixed interval had elapsed. If no response occurred
      during the interval, the fixed-ratio requirement decreased to one and a single
      response after the interval elapsed produced food. The initial value of the
      adjusting fixed-ratio schedule was studied over a range of 0 to 900. Increases in
      the adjusting fixed-ratio schedule to about 300 responses increased both pause
      duration and running response rate and also modified the pattern of responding
      from that obtained under the fixed-interval schedule. Higher values of the
      adjusting fixed ratio generally decreased pause duration and running response
      rate and also disrupted responding. Interreinforcement time under the conjunctive
      schedule was increased substantially when the adjusting fixed-ratio size exceeded
      300 responses.

PMID- 16811900
TI  - Some conditions affecting the choice to cooperate or compete.
AB  - Three experiments investigated conditions affecting the choice to cooperate or
      compete. Experiment I compared the effects first of an individual activity, then
      of a competitive task as an alternative to cooperation. For both comparisons,
      subjects could earn more by cooperating. Choice of competition, but not
      individual activity, was found to depend on the task choice contingencies.
      Competition predominated when both subjects could compete if either or both chose
      competition. Previously competitive pairs cooperated when both subjects could
      cooperate if either or both chose cooperation. Experiment II investigated the
      effects of differences in magnitude of the reinforcers for cooperating or
      competing. Choice between the two alternatives was manipulated in all pairs by
      varying reinforcer difference. Competition was chosen over cooperation only
      within the limits within which competition was potentially profitable. Experiment
      III replicated the findings of Experiment II using triads. Subjects in triads,
      however, were more likely to withdraw from the experiment. Thus, the data for
      pairs and triads suggest an orderly relation between reinforcer difference for
      cooperating or competing and task choice. Motivation of subjects to maximize
      relative gain by competing can be overridden by moderate reinforcer differences
      favoring cooperation.

PMID- 16811901
TI  - Behavioral contrast of time allocation.
AB  - Pigeons' standing on a platform produced food reinforcement according to two
      component multiple schedules in which either both components consisted of the
      same variable-interval schedule or one of these was replaced with a component
      without reinforcement (extinction). The components of the multiple schedule
      alternated every 30 sec, and were signalled by changes in the color of diffuse
      overhead illumination. Changing the schedule of one of the components to
      extinction increased the percentage of time spent on the platform during the
      unchanged component (behavioral contrast). This result casts doubt on accounts
      that attribute behavioral contrast to variations in the rate of noninstrumental
      elicited responses.

PMID- 16811902
TI  - Contrast, induction, facilitation, suppression, and conservation.
AB  - Ten rats received all of their water in daily 1-hr sessions. Following a baseline
      phase in which lever and water spout were freely available throughout each
      session, subjects were trained to press the lever for water on mixed schedules
      composed of two alternating components. Each component gave access to water for a
      fixed cumulation of drinking time every time the rat cumulated a fixed amount of
      lever-pressing time. Changes in one component produced contrast and induction
      effects, both positive and negative, with respect to both lever pressing and
      drinking in the unchanged component. All schedules facilitated lever pressing
      relative to baseline. All schedules suppressed drinking relative to baseline,
      even though contingency sessions allowed ample time to perform the baseline
      amount of drinking. The entire pattern of results was predicted in quantitative
      detail by assuming that the total amount of a dimension apportioned to lever
      pressing and drinking is conserved between baseline and contingency sessions.
      Conservation theory was shown to predict several effects produced by simple fixed
      ratio schedules, and was compared favorably with probability-differential
      (Premack, 1971) and response-deprivation (Timberlake and Allison, 1974) theory.

PMID- 16811903
TI  - Stimulus control of differential-reinforcement-of-low-rate responding.
AB  - Five pigeons were given single-stimulus training on an 8-sec differential
      reinforcement-of-low-rate schedule followed by steady-state generalization
      training using 12 wavelength stimuli. Three birds had a high percentage of
      reinforced responses on the training schedule and flat generalization gradients
      of total responses. The birds with fewer reinforced responses had much steeper
      generalization gradients. Generalization gradients plotted as a function of both
      stimulus wavelength and interresponse time showed that for most birds, stimulus
      control was restricted to responses with long interresponse times. Responses with
      very short interresponse times were not under stimulus control and there was some
      evidence of inhibitory control of short interresponse times. Interresponse-times
      per-opportunity functions, plotted as a function of stimulus wavelength, showed
      that stimulus wavelength controlled the temporal distribution of responses,
      rather than the overall rate of response. The data indicate that the differential
      reinforcement-of-low-rate schedule generates several response categories that are
      controlled in different ways by wavelength and time-correlated stimuli, and that
      averaging responses regardless of interresponse-time length obscures this
      control.

PMID- 16811905
TI  - Farewell, My LOVELY!

PMID- 16811904
TI  - Stimulus duration as a measure of stimulus generalization.
AB  - Four pigeons in the line-positive group were trained with a vertical line on a
      green background that signalled intermittent reinforcement while a plain green
      field signalled extinction. Four pigeons in the line-negative group were trained
      with the opposite discrimination. Response to a control key terminated any trial
      and initiated the next trial. The birds also used the control key during
      generalization tests to control the durations of trials in which various line
      orientations were presented. These durations were summed to provide
      generalization gradients of stimulus duration that were positive or negative in
      accordance with the trained discriminations. In Experiment 2, birds from the line
      positive group were tested with a procedure in which the control key was not
      available on some trials. This provided an independent assessment of response
      rates to the test stimuli. These rates were used to predict the stimulus
      durations obtained when the control key was available. The findings supported a
      general model for the prediction of response distributions among concurrent
      stimuli from rates observed with single stimuli.

PMID- 16811906
TI  - Responding under positive and negative response contingencies in pigeons and
      crows.
AB  - Four crows were trained to key peck for food. Then, they were exposed to a
      positive response contingency that required them to peck the key when it was
      illuminated briefly (the trial) in order to receive food. This procedure resulted
      in consistent within-trial pecking. When the contingency changed so that food was
      presented at the end of a trial when no response occurred, but the trial
      terminated immediately and food was omitted when a response occurred (negative
      response contingency), responding decreased markedly. Eight pigeons were studied
      under the same change in contingencies. These birds varied in their response
      histories from naive to having several years' experience. The previously naive
      pigeons also showed rapid declines in responding under the negative contingency;
      the responding of the birds with extended training histories declined much more
      slowly. Eventually, however, six of the eight pigeons showed little or no
      responding under the negative contingency, while they responded consistently when
      re-exposed to the positive contingency. These findings question the power and the
      generality of the negative automaintenance phenomenon.

PMID- 16811907
TI  - A comparison of pecking generated by serial, delay, and trace autoshaping
      procedures.
AB  - Pigeons were exposed to serial, delay, and trace autoshaping procedures. In
      Experiment I, all conditioned stimuli (CSs) were changes in illumination of the
      response key. The number of trials to acquisition of the keypeck increased from
      serial, to 4-sec delay, 8-sec delay, and 8-sec trace procedures, in that order.
      In Experiment II, which used a longer intertrial interval, trials to criterion
      increased from 8-sec delay, to 28-sec delay, 8-sec trace, and 28-sec trace
      procedures, in that order. In Experiment III, two groups received serial
      procedures in which the first CS was either a tone or a houselight, and the
      second was a keylight. The tone group acquired the key peck more rapidly than the
      houselight group. Early in conditioning in these experiments, and when the
      conditioned stimulus was a change in the keylight, there was a short latency to
      the onset of pecking and pecking was directed at the CS. After extensive
      conditioning, or when the CS was relatively diffuse, pecking still occurred, but
      had a longer latency and was not reliably directed toward the conditioned
      stimulus.

PMID- 16811908
TI  - Response bias and the discrimination of stimulus duration.
AB  - Pigeons discriminated stimulus duration in a psychophysical choice situation.
      Following presentation of any duration from a set of short duration (11 to 15
      sec), responses on a red key were reinforced intermittently. Following
      presentation of any duration from a set of long durations (16 to 22 sec),
      responses on a green key were reinforced intermittently. Relative reinforcement
      rates were manipulated for choice responses across conditions. As relative
      reinforcement rates were varied, psychometric functions showed shifts in green
      key responses at all durations. A signal-detection analysis showed that
      sensitivity remained roughly constant across conditions while response bias
      changed as a function of changes in relative reinforcement rate. Relative error
      rates tended to match relative reinforcement rates.

PMID- 16811909
TI  - Preference for mixed versus constant delay of reinforcement.
AB  - Preference for constant and mixed delay of reinforcement was studied using
      concurrent equal variable-interval schedules. For four pigeons, pecking one key
      was reinforced following constant delays of 8 sec and mixed delays of 6 or 10 and
      2 or 14 sec. Pecking a second key was reinforced following constant delays of 0,
      8, 16, and 32 sec. For two additional pigeons, pecking one key was reinforced
      following delays of 30, 15 or 45, 5 or 55, and 0 or 60 sec. Reinforcements on the
      other key were delayed 30 sec. It was found that (a) pigeons preferred mixed
      relative to constant delay of reinforcement, and (b) preference for mixed delay
      of reinforcement increased as the range of delay interval variability increased.

PMID- 16811910
TI  - Effects of signals preceding and following shock on baseline responding during a
      conditioned-suppression procedure.
AB  - Long-Evans rats were exposed to a succession of conditioned-suppression
      procedures involving pairings of (1) signal-shock, (2) shock-signal, and (3) a
      signal-shock-signal sequence in which first and second signals were at first
      physically identical. Traditional suppression of food-reinforced responding was
      obtained under the signal-shock arrangement, and exposure to the shock-signal
      sequence resulted in conditioned enhancement of responding during the signal. The
      signal-shock-signal condition reliably suppressed responding during the first
      signal, but produced no differential effect on response rate during the second
      signal. Baseline responding was least changed from preshock rates under the
      signal-shock-signal procedure, but baseline rate was considerably reduced under
      the signal-shock and shock-signal arrangements, the latter yielding most
      substantial reductions. A second experiment indicated that the magnitude and
      direction of changes in baseline responding reported in Experiment I were not
      confined to cases in which the first and second signals in the signal-shock
      signal arrangement were physically identical. It is suggested that the major
      effects of the conditioned-suppression procedure on response rate might not be
      confined to presentations of the signal.

PMID- 16811911
TI  - Detection of water level in inverted bottles.

PMID- 16811912
TI  - The effects of a cooperation contingency on behavior in a continuous three-person
      environment.
AB  - Five groups of three subjects resided for 10 or 15 days within a continuously
      programmed environment. Subjects followed a programmatic arrangement of required
      and optional private and social activities that determined the individual and
      group baseline behaviors into which experimental operations were introduced and
      withdrawn. A cooperation condition was in effect when all three subjects were
      required to select simultaneous access to a group area before it became available
      for use. A noncooperation condition was in effect when access to a group area
      could be selected by individual subjects, without regard to the other subjects'
      selections. For all groups, the effects of these two conditions on individual and
      group behaviors were investigated in reversal designs where several successive
      days occurred under each condition. Groups 1, 4, and 5 had the noncooperation
      condition interposed between cooperation conditions. Groups 2 and 3 had the
      cooperation condition interposed between noncooperation conditions. Durations of
      triadic activities, per cent of time in triadic activities, intercom use, and
      intersubject program synchronization were greater during cooperation conditions
      than during noncooperation conditions. These data show that a cooperation
      contingency within the behavioral program affected both social behavior and the
      collateral individual behavior necessary to execute the cooperation response.

PMID- 16811913
TI  - Sequential reacquisition as a function of timeout from avoidance.
AB  - Rats learned to reacquire four similar three-member response sequences. Each
      sequence member was associated with a different response lever, and the correct
      sequence of levers (i.e., 3-1-2, 2-1-3, 1-3-2, and 2-3-1) changed each session.
      The first two correct responses of each sequence postponed shock for a fixed
      period of time. The third correct response initiated a signalled timeout from
      avoidance. Incorrect responses did not affect the shock interval or reset the
      sequence. The effects of manipulating timeout duration on the sequential
      reacquisition baseline were investigated. All subjects displayed biphasic
      reacquisition performances similar to those controlled by food. The phases were
      characterized by an initial increase in accuracy, which reached a stable level
      during the latter portion of each session. Timeout duration affected rate of
      sequence completion and shock density, but not percentage of errors. Rate of
      sequence completion was fastest with intermediate timeouts (15 to 60 sec), and
      slowest with extreme durations (1 or 120 sec). Shock densities peaked with
      extreme durations and were at minimum with intermediate timeout values. The
      percentage of errors was the same across timeout durations. These data extend the
      generality of sequential reacquisition as a procedure for studying learning, and
      demonstrate timeout from avoidance to be a controlling variable.

PMID- 16811914
TI  - Alternative response training, differential reinforcement of other behavior, and
      extinction in squirrel monkeys (Saimiri sciureus).
AB  - In Experiment I, (a) extinction, (b) extinction plus reinforcement of a discrete
      alternative response, and (c) differential reinforcement of other behavior were
      each correlated with a different stimulus in a three-component multiple schedule.
      The alternative-response procedure more rapidly and completely suppressed
      behavior than did differential reinforcement of other behavior. Differential
      reinforcement of other behavior was slightly more effective than extinction
      alone. In Experiment II, reinforcement of specific alternative behavior during
      extinction and differential reinforcement of other behavior were used in two
      components, while one component continued to provide reinforcement for the
      original response. Once again, the alternative-response procedure was most
      effective in reducing responding as long as it remained in effect. However, the
      responding partially recovered when reinforcement for competing behavior was
      discontinued. In general, responding was less readily reduced by differential
      reinforcement of other behavior than by the specific alternative-response
      procedure.

PMID- 16811915
TI  - Effects on responding of mixed and multiple schedules of signalled and
      unsignalled response-dependent electric-shock delivery.
AB  - Responding in two rats was maintained under mixed and multiple variable-interval
      35-sec variable-interval 35-sec food delivery schedules. Similar rates and
      patterns of responding occurred in each component of the two schedules. Mixed and
      multiple variable-interval 65-sec variable-interval 65-sec schedules of response
      dependent shock delivery were super-imposed on the mixed and multiple baseline
      food schedules, respectively. In one component, a 5-sec stimulus was presented on
      the average of once every 65 sec. Offset of the stimulus arranged that the next
      response would produce shock. In the other component, no stimulus was presented
      during the 5-sec period. The mixed schedule of signalled and unsignalled
      dependent shock delivery yielded similar degrees of response suppression in each
      component, but the multiple schedule of shock delivery revealed differential
      degrees of response suppression. Considerably more suppression occurred in the
      component not associated with the preshock stimulus, thus implicating the
      discriminative functions of the correlated stimulus.

PMID- 16811916
TI  - A temporal parameter influencing choice between signalled and unsignalled shock
      schedules.
AB  - The present study investigated whether choice of a signalled variable-time shock
      schedule over an unsignalled one was influenced by the average intershock
      interval. Eight rats were given a choice between signalled and unsignalled shock
      schedules in a series of conditions with average intershock intervals of 510,
      270, 150, 90, 60, and 45 sec. Each test condition was preceded by a training
      baseline condition, and schedule values were arranged in an ascending (four
      subjects) or descending (four subjects) order. Choice of the signalled conditions
      was directly related to the average intershock interval of the variable-time
      schedule for six of the eight subjects. The per cent of time in the signalled
      condition was highest when the average intershock interval was 150 sec or longer
      and lowest when the average intershock interval was 45 sec. The findings were
      interpreted as being due to changes in the safety features of the signalled
      schedule, rather than to changes in the average intershock interval per se.

PMID- 16811917
TI  - Performance on variable-interval schedules arranged singly and concurrently.
AB  - Extensive parametric data were obtained from pigeons responding on variable
      interval schedules arranged on three, two, and one response keys. Number of
      responses on the keys, the time spent responding on the keys, and the number of
      reinforcements obtained on the keys were measured. Response rates on each key
      were an increasing function of the reinforcement rate on that key, and an inverse
      function of the reinforcement rate on the other keys. In terms of preference,
      both response and time-allocation ratios undermatched ratios of obtained
      reinforcements, and the degree of undermatching was consistent both within, and
      between, two- and three-schedule data. When absolute response-rate data were
      analyzed according to Herrnstein's (1970) quantitative account, obtained values
      of assumed constants were not consistent either within or between conditions.
      However, a power-function modification of Herrnstein's account fitted the data
      well and provided similar exponent values to those obtained for the undermatching
      of preference ratios.

PMID- 16811918
TI  - Aftereffects of reinforcement on variable-ratio schedules.
AB  - On each of variable-ratio 10, 40, and 80 schedules of reinforcement, when rats'
      lever-pressing rates were stable, the concentration of a liquid reinforcer was
      varied within sessions. The duration of the postreinforcement pause was an
      increasing function of the reinforcer concentration, this effect being more
      marked the higher the schedule parameter. The running rate, calculated by
      excluding the postreinforcement pause, was unaffected by concentration. The
      duration of the postreinforcement pause increased with the schedule parameter,
      but the proportion of the interreinforcement interval taken up by the pause
      decreased. Consequently, the overall response rate was an increasing function of
      the schedule parameter; i.e., it was inversely related to reinforcement
      frequency, contrary to the law of effect. The running rate, however, decreased
      with the reinforcement frequency, in accord with the law of effect. When 50% of
      reinforcements were randomly omitted, the postomission pause was shorter than the
      postreinforcement pause, but the running rate of responses was not affected.

PMID- 16811919
TI  - Acquisition of the autoshaped key peck as a function of amount of preliminary
      magazine training.
AB  - Three experiments evaluated the effect of magazine training on acquisition of the
      pigeon's key peck during autoshaping. In Experiment I, pigeons were exposed to
      two days of extended magazine training, followed on the third day by keylight
      only presentations. All pigeons pecked the keylight early in the keylight-only
      session. Experiment II examined the relationship between the number of magazine
      training trials and trials to the first peck. Pigeons were given either 0, 3, 10,
      or 25 magazine-training trials followed by the standard autoshaping procedure.
      The number of trials to the first peck was related to the number of magazine
      training trials. In Experiment III, pigeons were exposed to the standard
      autoshaping procedure without prior magazine training. The data from Experiment
      III suggested that key pecking will occur only after the response of eating from
      the lighted hopper has occurred. Taken together, these results suggest that
      initial magazine training is an important variable in autoshaping. Key pecking is
      discussed as a generalized consummatory response.

PMID- 16811920
TI  - An analysis of rats' drinking-tube contacts under tandem and fixed-interval
      schedules of food presentation.
AB  - Rats' lever presses and drinking-tube contacts were studied under fixed-interval
      schedules of food presentation and under a tandem schedule composed of three
      fixed intervals. One group of rats was exposed first to the tandem schedule, next
      to fixed-interval schedules of comparable interpellet intervals, and once again
      to the tandem schedule; a second group of rats was exposed first to a fixed
      interval and then to the tandem schedule. Under the tandem schedule, lever
      presses occurred at a higher rate and were more uniformly distributed in time
      than under the fixed-interval schedule. Tube contacts emitted by rats exposed
      first to a fixed-interval schedule consisted mostly of tongue contacts, which
      occurred at a high rate shortly after food; tube contacts emitted by rats exposed
      first to the tandem schedule consisted mostly of paw contacts, which occurred at
      a lower rate at times other than shortly after food. Changing the schedule from
      fixed interval to tandem decreased the frequency of tongue contacts for all rats.
      Under schedules of food presentation with comparable interpellet intervals, the
      schedule of food presentation, rather than the rate of food delivery per se,
      determined the topography and temporal locus of drinking-tube contacts.

PMID- 16811921
TI  - Preference for fixed-interval schedules: effects of unequal initial links.
AB  - Six homing pigeons were trained on concurrent chain schedules in which the
      terminal links were fixed-interval schedules of 5 sec or 15 sec. One initial-link
      schedule was always VI 27-sec; the other was varied over conditions from VI 27
      sec to VI 181-sec. Preference measured in the initial links varied as a joint
      function of the initial- and terminal-link schedules. When the initial links were
      varied with constant, but unequal, terminal links, the slope of the function
      relating the logarithm of the initial-link response ratio to the logarithm of the
      terminal-link entry ratio differed from that obtained with equal terminal links.
      This result indicates that biases attributable to the terminal-link schedules
      were not constant. The rate of change of preference, or degree of undermatching,
      in the initial links depended on whether the shorter initial link led to the
      shorter or the longer terminal link. These results raise the question of whether
      bias and undermatching in concurrent schedule performance are independent
      measures.

PMID- 16811922
TI  - Concurrent performances: rate constancies without changeover delays.
AB  - Pigeons' pecks on two keys were maintained, without changeover delays, by
      independent variable-interval schedules of food reinforcement. Four regularly
      cycling 2-min components scheduled reinforcement respectively for both keys, left
      key only, both keys, and right key only. Initially, reinforcement scheduled for
      one key alone produced more responding on that key than reinforcement scheduled
      concurrently for both keys. Continued sessions reduced this difference; response
      rate on a given key approached constancy, or invariance with respect to the
      performance on and schedule for the other key. When extinction replaced the
      reinforcement schedule on either key, responding on that key decreased more
      during components that scheduled reinforcement for the other key than during
      those that did not. This demonstration that responses on one key were not
      supported by reinforcers on the other key suggested that the alternation of
      concurrent responding and either-key-alone responding prevented concurrent
      superstitions from developing.

PMID- 16811923
TI  - Operant conditioning in nondeprived adult and infant guinea pigs.

PMID- 16811924
TI  - The associative relation underlying autoshaping in the pigeon.
AB  - Fifteen pigeons were exposed to either response-independent or response-dependent
      schedules of water reinforcement, whereby water was injected directly into the
      unrestrained pigeons' mandibles. Key-contact responses were released by a lighted
      key correlated with water, but not by a lighted key uncorrelated with water. A
      negative response-reinforcer contingency suppressed autoshaped key-contact
      responses, resulting in responding directed away from the lighted key. In all
      pigeons, water injected directly into the mandibles elicited a consummatory fixed
      action pattern of "mumbling" and swallowing. The lighted key correlated with
      water released a broader set of both appetitive and consummatory responses:
      approach to the lighted key, "bowing", "rooting", "mumbling", and swallowing. Key
      contact responses were "rooting" and "mumbling" motions of the beak on the
      surface of the key. Views of autoshaping based on stimulus substitution or
      stimulus surrogation do not fully explain the origin of autoshaped responses not
      previously elicited by the reinforcer. The present findings are consonant with
      views of conditioning that emphasize the large degree of biological pre
      organization in conditioned response patterns, and the importance of associative
      factors in the control of such patterns.

PMID- 16811925
TI  - Organization in memory and behavior.
AB  - SOME COMMON REINFORCEMENT CONTINGENCIES MAKE THE DELIVERY OF A REINFORCER DEPEND
      ON THE OCCURRENCE OF BEHAVIOR LACKING SIGNIFICANT TEMPORAL STRUCTURE: a
      reinforcer may be contingent on nearly instantaneous responses such as a pigeon's
      key peck, a rat's lever press, a human's button press or brief verbal utterance,
      and so on. Such a reinforcement contingency conforms much more closely to the
      functionalist tradition in experimental psychology than to the structuralist
      tradition. Until recently, the functionalist tradition, in the form of a kind of
      associationism, typified most research on human learning and memory. Recently,
      however, research on human memory has focused more on structural issues: now the
      basic unit of analysis often involves an organized temporal pattern of behavior.
      A focus on the interrelations between the function and structure of behavior
      identifies a set of independent and dependent variables different from those
      identified by certain common kinds of "molar" behavioral analyses. In so doing,
      such a focus redefines some of the significant issues in the experimental
      analysis of behavior.

PMID- 16811926
TI  - An inexpensive random-access projector for rapid presentation of pictorial
      images.

PMID- 16811927
TI  - Scaling of stimulus duration by pigeons.
AB  - Pigeons were presented with a series of key-illumination time periods. During
      these periods two response keys were lit, one by white light and the other by red
      or green. White-key responses changed the color on the other key and green- and
      red-key responses intermittently produced food. Choice responses were reinforced
      at either of two intervals timed from the onset of the stimulus period. Food was
      scheduled for green responses during the shorter interval in some stimulus
      periods and food was scheduled for red-key responses at the longer interval
      during alternate stimulus periods. The temporal location of food in the stimulus
      periods was varied across conditions. Across conditions, the pigeons responded on
      the green key until the time at which green-key responses might be reinforced had
      passed; then, the probability of red-key responses increased as the time
      approached at which red-key responses might be reinforced. In all conditions, the
      pigeons, changed from green-key to red-key responses at the time that was an
      equal relative temporal distance from the two intervals where these responses
      were reinforced.

PMID- 16811928
TI  - Time-based and count-based measurement of preference.
AB  - Rats' pressing on two levers was reinforced according to two independent variable
      interval schedules that were varied during the experiment. Since the levers were
      connected directly to the programming equipment, bypassing the standard
      pulseformers, reinforcement could occur while a lever was held down. Although the
      time a lever was pressed might, therefore, have varied independently of number of
      presses, these two measures covaried substantially, because the average duration
      of the presses remained roughly constant. This rough invariance may have resulted
      from the rats' tendency to make bursts of brief presses (i.e., to jiggle the
      levers), even though the contingencies encouraged holding. When duration did
      vary, presses on the two levers tended to vary together. As a result, relative
      time spent pressing corresponded closely to relative number of presses. Both of
      these measures conformed well to the matching law. Absolute behavioral frequency
      at a lever, measured either way, varied directly with proportion of reinforcement
      for that lever, in accordance with the generalized version of the matching law.
      Number of presses seemed, on balance, to be a slightly more reliable measure than
      pressing time. The substantial interchangeability may prove more significant than
      the slight disparity, however, because it supports the notion that all behavior
      can be measured on a common scale of time.

PMID- 16811929
TI  - Positive reinforcement and the elimination of reinforced responses.
AB  - Key pecking was maintained on a fixed-interval schedule while either a
      differential-reinforcement-of-not-responding or a fixed-time schedule was imposed
      simultaneously. The lower the time parameter of the not-responding schedule, the
      lower was the response rate. Similar effects occurred with the fixed-time
      schedule, if the pigeons had experience with reinforcement for not responding.
      Otherwise the effects were less orderly, to the extent that rate could reach
      maximum with the lowest-valued fixed-time schedule. The not-responding and the
      response-independent schedules had similar effects on rate in experienced pigeons
      only when the time parameter or nominal frequency of food presentation was
      considered. When considered in terms of obtained frequency of food presentation,
      reinforcement of not responding produced larger decrements in rate than did the
      fixed-time schedule.

PMID- 16811930
TI  - A test of the reinforcing properties of stimuli correlated with nonreinforcement.
AB  - The information hypothesis of conditioned reinforcement predicts that a stimulus
      that "reduces uncertainty" about the outcome of a trial will acquire reinforcing
      properties, even when the stimulus reliably predicts nonreinforcement. Four
      pigeons' key pecks produced one of two 5-sec stimuli with 0.50 probability
      according to a discriminated variable-interval schedule. One stimulus was
      followed by reinforcement; a second stimulus was followed by blackout. To the
      same extent, therefore, both stimuli reduced uncertainty about the possibility
      that food would arrive at the termination of the schedule interval. When a second
      key in the chamber was lighted, each peck on it could produce the stimulus
      preceding reinforcement, the stimulus preceding nonreinforcement, a novel
      stimulus, or no stimulus, across separate conditions. The stimulus preceding food
      maintained responding at substantial levels on the second, stimulus-producing,
      key. Such responding was not maintained by other stimuli. These data, replicated
      when the stimuli were reversed on the variable-interval schedule, do not support
      the prediction that uncertainty-reducing stimuli are necessarily conditioned
      reinforcers.

PMID- 16811931
TI  - Behavioral contrast as a function of the temporal location of reinforcement.
AB  - Pigeons were trained on a multiple variable-interval variable-interval schedule
      of reinforcement. One component was then changed to a variation of a fixed
      interval schedule in which the same rate of reinforcement was obtained as
      previously but the location of the reinforcer was fixed within the component. The
      effects of different temporal locations were compared. An increase in response
      rate for the unchanged variable-interval component (behavioral contrast) occurred
      when the reinforcer was located in the middle or at the end of the FI component,
      but response suppression occurred when it was located at the beginning of the
      component. The pattern of results cannot be explained by any previous theories of
      contrast. The overall response rates, and the pattern of local rates within the
      components, were consistent with the hypothesis that the major determinant of the
      contrast effect was the transition to a lower reinforcement rate following the
      unchanged component.

PMID- 16811932
TI  - Successive discrimination training with equated reinforcement frequencies:
      failure to obtain behavioral contrast.
AB  - In two experiments, pigeons were trained on two-component multiple schedules in
      which responding in one component (S(1)) was always maintained by a variable
      interval schedule. In Experiment I, low response rates were reinforced in the
      second (S(2)) component for six master subjects. This schedule was adjusted to
      equate reinforcement frequencies in the two components. These subjects were
      compared to yoked partners, for which reinforcement in the S(2) component was
      made available on a variable-interval schedule whose value was determined by the
      master subjects. A similar procedure was used in Experiment II, where the S(2)
      schedule for master subjects made reinforcers contingent on the absence of
      responding. No evidence was found in either experiment for a behavioral contrast
      effect in the S(1) component attributable to response reduction in the S(2)
      component. A reliable contrast effect was obtained from a group of pigeons given
      extinction conditions in the S(2) component, which was compared to a group
      maintained throughout on a multiple variable-interval schedule. The results
      suggest that previous indications of behavioral contrast in similar situations
      were probably caused by uneven reinforcement distributions or reflect
      uncontrolled fluctuations in response rates.

PMID- 16811933
TI  - Interactions in multiple schedules: the role of the stimulus-reinforcer
      contingency.
AB  - In Experiments I and II, pigeons were exposed to single-key multiple schedules of
      response-independent and -dependent food presentation. Components were correlated
      with different keylights. When the rate of food presentation in the first
      component exceeded that in the second component, the local rate of key pecking
      was relatively high at onset of the first component. Overall rate in that
      component varied inversely with component duration and the rate of food
      presentation in the second component. When responding was maintained in the
      second component, the local rate of key pecking was relatively low at onset of
      that component. Overall rate in the second component varied directly with
      component duration and the rate of food presentation in that component. In
      Experiment III, pigeons were exposed to a two-key multiple schedule. Pecks on a
      constantly illuminated key produced food. Components were correlated with the
      color of a second key on which pecks had no scheduled consequences. The effects
      of component duration and rate of food presentation under the single-key response
      dependent schedule were synthesized by combining response rates on each
      concurrently available key under the two-key procedure. The results support an
      account of multiple-schedule interactions in terms of the joint influence on
      responding of stimulus-reinforcer and response-reinforcer contingencies.

PMID- 16811934
TI  - Choice and the dependability of stimuli that predict shock and safety.
AB  - This study assessed whether choosing a signalled shock condition over an
      unsignalled one is controlled by a stimulus that predicts the presence of shock
      (Experiment I), or by a stimulus that predicts the absence of shock (Experiment
      II). The dependability of these stimuli as predictors of either the presence or
      the absence of shock was parametrically varied over a wide range, and subjects
      (rats) were given an option to change from an unsignalled to a signalled
      condition. In the first experiment, all shocks were preceded by signals; however,
      the probability of a signal being followed by shock varied from 1.0 to 0.02. The
      data obtained indicate that the dependability of the signal as a predictor of
      shock is unimportant. Rats changed to the signalled condition when the signal was
      completely dependable (all signals followed by shock) and when the dependability
      of the signal was systematically degraded. In the second experiment, all signals
      were followed by shock; however, some shocks were not preceded by a signal. The
      data show that the dependability of a stimulus predicting the absence of shock is
      important in that, as dependability decreases, changing to the signalled
      condition also decreases.

PMID- 16811935
TI  - Behavior of humans in variable-interval schedules of reinforcement.
AB  - During Phase I, human subjects pressed a button for monetary reinforcement in
      five variable-interval schedules, each of which specified a different frequency
      of reinforcement. The rate of responding was an increasing, negatively
      accelerated function of reinforcement frequency; the data conformed closely to
      Herrnstein's equation. During Phase II, the same five schedules were in
      operation, but in addition a concurrent variable-interval schedule (B) was
      introduced, responses on which were always reinforced at the same frequency.
      Response rate in component A increased while the response rate in B decreased, as
      a function of the reinforcement frequency in component A. Relative response rates
      in the two component schedules matched the relative frequencies of reinforcement.
      Comparing the absolute response rates in component A during Phase I and Phase II
      it was found that introduction of the concurrent schedule did not affect the
      value of the theoretical maximum response rate, but did increase the value of the
      reinforcement frequency needed to obtain any particular submaximal response rate.

PMID- 16811936
TI  - Matching in a network.
AB  - Pigeons were given practice choosing between pairs of alternatives yielding
      different frequencies of reinforcement. Four individual alternatives were set
      into four pairwise choices. Averaged over subjects, the distribution of responses
      in each choice approximated matching. The four individual alternatives were then
      presented, two by two, in two pairwise choices for which there had been no
      initial practice. No further reinforcement was given during the tests with the
      new pairs. Transfer to the two test pairs deviated systematically from matching
      in most cases by exaggerating the preference for the alternative that had had the
      higher frequency of reinforcement.

PMID- 16811937
TI  - Effects of variations in the temporal distribution of reinforcements on interval
      schedule performance.
AB  - Pigeons were exposed to variable-interval and fixed-interval schedules and
      schedules approximating variable-interval and fixed-interval schedules. The
      probabilities of the variable-interval and fixed-interval components in a mixed
      fixed-interval variable-interval schedule in Experiment I and the minimum and
      maximum interreinforcement intervals in Experiment II in a variable-interval
      schedule were manipulated to create intermediate schedule contingencies and
      contingencies approximating simple variable-interval or fixed-interval
      contingencies. Maximal control by time as defined by quantitative indices of the
      temporal pattern of response occurred as fixed-interval contingencies were
      approximated and minimal control occurred as variable-interval contingencies were
      approximated. Changes in the temporal pattern of response were systematically
      related to changes in the temporal distribution of reinforcements with both
      procedural definitions for manipulating the temporal distribution of
      reinforcements.

PMID- 16811938
TI  - Clock control of human performance on avoidance and fixed-interval schedules.
AB  - The avoidance and fixed-interval performances of human subjects were studied in
      two experiments. Addition of time-correlated stimuli (added clock) improved
      behavioral efficiency, since response rates decreased without decreases in
      reinforcement rates. Response-dependent display of the clock maintained a second,
      observing response and reductions in clock duration weakened such observing
      behavior. Generally, the reinforcing properties of the clock were more apparent
      with the avoidance than with the fixed-interval schedule, a finding attributed to
      temporal cues already provided by delivery of the fixed-interval reinforcers.
      Reduced rates of the main response when the clock was dependent on an observing
      response were more than offset by rates of the observing response in the majority
      of subjects. Thus, the results do not support an interpretation of the
      reinforcing properties of added clocks simply in terms of work reduction.

PMID- 16811939
TI  - Behavior changes during repeated eight-day extinctions.
AB  - Pigeons were given repeated two-day conditionings alternating with eight-day
      extinctions using a trial procedure. One group had different key colors during
      each of the first five conditioning-extinction pairs; another group had the same
      key color throughout. Total extinction responses of both groups were quite
      constant over successive extinctions. This finding differs from the rapid
      declines found in most previous studies with bar-press and key-peck responses.
      The difference probably was due to our longer extinctions, because responses
      early in each extinction did decrease. However, that decrease was neutralized by
      increases in responses late in each extinction. The two opposite changes indicate
      the influence of two different factors during repeated extinctions, with neither
      factor having much stimulus specificity. The reduction of early responses may
      result from feeding changes confounded with extinction. The increase in later
      extinction responses may result from a decrease in the effect of unreinforced
      responses after their repeated occurrence.

PMID- 16811940
TI  - Dimensional stimulus control following brief wavelength training.
AB  - Pigeons with extensive training pecking a key illuminated by a white line then
      had brief training with the key illuminated by 555 nanometers. This was
      immediately followed by a wavelength generalization test in extinction.
      Dimensional stimulus control about the training wavelength increased with the
      duration and number of reinforcements given on variable-interval 30-sec and
      variable-interval 10-sec schedules in Experiment I. In Experiment II, dimensional
      stimulus control was obtained after only 4 min of wavelength training from birds
      with prior and independent discrimination training. Experiment III provided
      groups equated in number of reinforcers with groups in Experiment I and two 8-min
      duration groups. Analyses, which included results from both Experiments I and
      III, showed that dimensional stimulus control increased: (a) more rapidly as a
      function of the duration of variable-interval 10-sec than variable-interval 30
      sec reinforcement; (b) at the same rate across variable-interval reinforcement
      schedules, as a function of the number of reinforcers available during brief
      wavelength training.

PMID- 16811941
TI  - Signalled reinforcement and multiple schedules.
AB  - The responses of four pigeons were first reinforced in the presence of two
      different wave-lengths (green and red) on a two-ply multiple schedule with
      identical variable-interval 3-min schedules of reinforcement associated with each
      component. While the constant-component reinforcement schedule remained unchanged
      during the experiment, the schedule associated with the variable component was
      changed to (1) signalled variable time, (2) unsignalled variable time, or (3)
      signalled variable interval. The probability with which the availability of the
      reinforcer was signalled in the variable-interval schedules was either 0.5 or
      1.0. Positive contrast occurred in both signalled variable-interval and variable
      time schedules, but only when the availability of all the variable-component
      reinforcers was signalled. Signalling the availability of only 50% of the
      reinforcers in signalled variable-interval schedules resulted in negative
      induction. The present data suggest that positive behavioral contrast resulting
      from signalled reinforcer availability is due to the presence of an extinction
      correlated stimulus.

PMID- 16811942
TI  - Attention in the pigeon: a reevaluation.
AB  - During training sessions, pigeons were successively exposed to compounds
      consisting of a white triangle on a red background and a white circle on a green
      background. Key pecking intermittently produced grain reinforcers in the presence
      of one form-color compound. Once key pecking was confined to the compound
      associated with reinforcement, the elements-red, green, triangle, and circle-were
      presented during a test in which no reinforcement was available. Each bird pecked
      nearly exclusively in the presence of the color previously associated with
      reinforcement, a result that might be interpreted as indicating that the subjects
      had attended to color, but not form during training. Pecking was next reinforced
      when either the triangle or the circle was present. Pecking in the presence of
      the form previously associated with reinforcement was acquired more rapidly. This
      result suggests that the birds had learned about the forms during training, and
      that conclusions about attention based on the lack of differential pecking in the
      nonreinforcement test may not be appropriate.

PMID- 16811943
TI  - Elicited responding to signals for reinforcement: the effects of overall versus
      local changes in reinforcement probability.
AB  - Pigeons were studied on a three-component multiple schedule where all
      reinforcement was independent of responding. Two components were cued by
      different keylights and were associated with different rates of reinforcement.
      The third was always a no-key period associated with extinction. After a few
      sessions, pecking was elicited by the keylights signalling the reinforcement and
      continued to be maintained indefinitely. The duration and sequence of the three
      components were varied to determine if the primary controlling variable was
      differences in the overall probability of reinforcement, or if it was the
      immediate change in reinforcement signalled by the onset and/or offset of the
      stimulus. Both variables were found to control behavior. When 30-sec components
      were used, the primary controlling variable was the overall probability of
      reinforcement, but when 3-min components were used, overall probability had
      little effect. Control by local changes in reinforcement also occurred, although
      the type of local control varied both across subjects and experimental
      conditions. Some behaviors were controlled more by the change in reinforcement
      signalled by the onset of the stimulus, while others were controlled more by the
      change signalled by the offset of the stimulus.

PMID- 16811944
TI  - Effects of a delay-reinforcement procedure on performance under IRT>t schedules.
AB  - Water-deprived rats were studied under a compound schedule that prescribed that
      responses terminating interresponse times (IRTs) greater than a fixed value t(1)
      (IRT > t(1) component schedule) initiated a delay of reinforcement interval t(2),
      at the end of which water was presented if the subject did not respond (R > t(2)
      component schedule). If the subject responded before the t(2) interval elapsed,
      the IRT > t(1) component schedule was re-initiated and water was not presented.
      The IRT > t(1) and R > t(2) component schedules were not differentially
      correlated with distinctive stimuli. Rate of responding during the IRT > t(1)
      component decreased as a function of the value of t(2). The magnitude of the
      decreases in response rate appeared to be proportional to the subject's rate
      under the IRT > t schedule with no delay of reinforcement (t(2) = 0 sec). The
      effects were independent of the parameter value of the IRT > t(1) component
      schedule and of the rate of reinforcement. The results suggested that
      "efficiency" of performance under IRT > t schedules can be increased by
      appropriately arranging brief delays of reinforcement.

PMID- 16811945
TI  - A comparison of the key-peck and treadle-press operants in the pigeon:
      differential-reinforcement-of-low-rate schedule of reinforcement.
AB  - Key pecking and treadle pressing in pigeons were compared under concurrent (key
      treadle) and single-operant differential-reinforcement-of-low-rate schedules of
      food reinforcement ranging from 5 to 60 sec (concurrent procedure) or 5 to 120
      sec (single-operant procedure). Under both procedures, the two operants followed
      the same general law: decreasing response rate and reinforcement rate and
      increasing number of responses per reinforcement as a function of increasing
      schedule interval. High correlations were found between key pecking and treadle
      pressing for the measures of response rate, reinforcement rate, and responses per
      reinforcement. Regression equations allowed the prediction of treadle pressing
      from key pecking. More bursting occurred in responding to the key, and key
      pecking showed a more precise temporal discrimination than treadle pressing. A
      test for sequential dependencies between key and treadle responses showed
      significant dependencies not only under the concurrent procedure but also in data
      created artificially by merging key and treadle sequences from different pigeons
      under the concurrent procedure and from the same pigeon under the single-operant
      procedure. It seems likely that the sequential dependencies found were due to the
      independent action of the schedule on each operant and that behavioral
      dependencies did not occur with the concurrent training procedure. The key-peck
      operant does not appear to have any special qualities that preclude its use in
      discovering general laws of behavior, at least under the differential
      reinforcement-of-low-rate schedule. The usefulness of the key peck in other
      situations requires direct experimental study.

PMID- 16811947
TI  - The effect of rearing environments on the contrafreeloading phenomenon in rats.
AB  - Eight naive rats were reared in enriched or impoverished environments for 39 days
      after weaning and then lived in operant chambers, in which they could obtain food
      pellets freely or by lever pressing, for 25 or 30 days. The animals raised in an
      impoverished environment acquired the bar-press response quickly when placed in
      the operant chambers and maintained a preference for obtaining food via bar
      pressing. Animals raised in an enriched environment did not learn to lever press,
      as demonstrated by low levels of responding and the lack of bar pressing when
      free food was subsequently removed. It was concluded that restricting animals'
      postweaning environments facilitated learning in a choice situation, probably
      because of increased activity levels. The results are interpreted in relation to
      previous studies on rearing environments and on contrafreeloading.

PMID- 16811946
TI  - Schedule-induced drinking as a function of interreinforcement interval in the
      rhesus monkey.
AB  - Lever presses by two rhesus monkeys produced food pellets that were assigned by
      both an ascending and descending series of fixed-interval schedules whose values
      varied between 1 and 512 sec. The amount of schedule-induced drinking was
      bitonically related to interreinforcement interval, reaching a maximum at
      approximately 120 sec and declining at longer fixed intervals. The relation
      between water intake and interreinforcement interval was complexly related to two
      drinking measures: (1) the probability of drinking following a pellet and (2) the
      amount drunk per bout. Drinking rate was also bitonically related to
      interreinforcement interval.

PMID- 16811948
TI  - The stages of acquisition in stimulus fading.
AB  - Pigeons were exposed to a stimulus fading procedure in which control of
      responding was transferred from red and black stimuli to lines of different
      angular orientation. After superimposing one line on the red stimulus and the
      other line on the black stimulus, the intensity of the lines was gradually
      increased and that of the red stimulus was gradually reduced. Probes consisting
      of red and line stimuli presented separately were used during the course of
      fading to assess control exerted by each element of the compound. As the lines
      were faded in, they did not acquire control of responding. As red was faded out,
      control of responding was acquired first by the lower intensity red stimuli in
      combination with the line stimulus, and finally by the angular orientation of the
      lines. Probes also determined the point at which the line stimuli, presented
      alone, would maintain a high degree of stimulus control. The results demonstrated
      that new stimuli in fading acquire dimensional control of responding in two
      sequential stages. Acquisition of stimulus control in fading was explained in
      terms of attenuation of stimulus blocking.

PMID- 16811949
TI  - Differential sample response schedules in the acquisition of conditional
      discriminations by pigeons.
AB  - Pigeons were trained on four matching-to-sample tasks with various schedule
      requirements in effect on the sample key. Differential sample-schedule
      requirements (a differential-reinforcement-of-low-rates of 3 sec in the presence
      of one sample and a fixed-ratio 16 in the presence of the other) produced rapid
      rates of acquisition that did not differ across tasks. Nondifferential sample
      schedule requirements (fixed-ratio 1, fixed-ratio 16 or a differential
      reinforcement-of-low-rates of 3 sec in the presence of both samples) produced
      slower rates of acquisition, which depended on the difficulty of the
      discriminations between samples and between comparisons. Patterns of stimulus and
      position preferences were influenced both by the comparison stimuli in each task
      and by the sample-schedule requirements. Detailed analyses of acquisition
      revealed frequent instances of complete differential sample control of comparison
      responding at intermediate levels of overall "accuracy".

PMID- 16811950
TI  - On attending at the "having" of reviews.

PMID- 16811951
TI  - Producing a change from competition to sharing: effects of large and adjusting
      response requirements.
AB  - Pairs of high-school students matched-to-sample for money. On each trial, the
      first pair member to complete a fixed ratio of knob-pulling responses could work
      the matching problem on that trial. Competition occurred when both pair members
      responded for the problem. Sharing occurred when only one pair member responded
      on each trial, and the subjects alternated trials. Hence, sharing requires less
      responding and still allows a moderate number of reinforcers for each subject.
      Recent research has shown that increasing the response requirement to the point
      that it may have aversive properties will produce a change from competition to
      sharing. A related variable is an adjusting schedule that adjusts the subjects'
      response requirements so that their abilities to take reinforcers are equal. In
      this way, subjects might learn that competition requires more responding but
      produces no more reinforcers. However, recent research also suggests that
      competition decreases over sessions without experimental manipulations. Because
      of this possibility of a time-related variable, ratio size and an adjusting
      schedule were studied in a group design. Competition did decrease for all groups
      over sessions, but the large-ratio groups switched from competition to sharing
      sooner than the low-ratio groups. The adjusting schedule had a similar but
      smaller effect.

PMID- 16811952
TI  - Matching-based hedonic scaling in the pigeon.
AB  - Four slightly hungry pigeons chose between pairs of grains in a Findley
      concurrent choice procedure. For Condition I, choice involved hemp versus
      buckwheat; for Condition II, wheat versus buckwheat; and for Condition III, hemp
      versus wheat. In all conditions, frequency of reinforcement was arranged
      according to concurrent variable-interval variable-interval schedules. On the
      assumption that subjects matched their behavior and time distributions to those
      of reinforcer value, the choice functions obtained in Conditions I and II were
      transformed to yield estimates of values of hemp and wheat relative to buckwheat.
      These, in turn, provided predictions about behavior and time allocation in
      Condition III. In general, the predicted outcomes were close to those actually
      obtained. The results evidence the effectiveness of matching-based hedonic scales
      in the prediction of choice between qualitatively different reinforcers.

PMID- 16811953
TI  - Integrated delays to shock as negative reinforcement.
AB  - Rats were shocked at the rate of two per minute until they pressed a lever. In
      Experiment I, shocks were delivered at variable-time intervals averaging 30 sec;
      in Experiment II, shocks were delivered at fixed-time intervals of 30 sec. A
      response produced an alternate condition for a fixed-time period. The shock
      frequency following a response, calculated over the whole alternate condition,
      was two per minute. The pattern of shocks in the alternate condition was
      controlled so that the first shock occurred at the same time as it would have
      occurred had the response not been emitted; the remaining shocks were delayed
      until near the end of the alternate condition. Bar pressing was acquired in both
      experiments. This finding is not explained by two-factor theories of avoidance
      and is inconsistent with the notion that overall shock-frequency reduction is
      necessary for negative reinforcement. The data imply that responding is
      determined by the integrated delays to each shock following a response versus the
      integrated delays to shock in the absence of a response.

PMID- 16811954
TI  - Force and rate relations in responding during variable-interval reinforcement.
AB  - Four rats responded on one-minute variable-interval schedules with several
      variations in peak-force of response required for food reinforcement. Measures of
      peak force and rate were taken for the responses, which were the downward
      exertions of force against a static force-transducing operandum. The analysis
      distinguished responses, a generic class of measured behavior, from criterion
      responses, an operationally specified subclass required for reinforcement.
      Absolute rate of response showed no systematic change, but the rate of responses
      meeting a newly required criterion of peak-force invariably increased through
      changes in the absolute rate of response, the relative-frequency distributions of
      peak force, or some combination of both. The relative frequency of responses
      meeting an elevated force criterion during variable-interval reinforcement
      exceeded that maintained with the same criterion with continuous reinforcement.
      The requirement of more effortful responding for reinforcement does not
      necessarily reduce response rate. Conformity of the behavior to the requirement
      for reinforcement is the salient effect.

PMID- 16811955
TI  - Factors influencing responding under multiple schedules of conditioned and
      unconditioned reinforcement.
AB  - Two experiments examined pigeons' responses under multiple schedules of
      conditioned and unconditioned reinforcement. In one component, responses produced
      food according to a fixed-interval schedule; in a second component, responses
      produced brief stimuli according to a fixed-ratio schedule. When brief-stimulus
      presentations were paired with food in the first component, rates in the second
      component were usually higher than 10 responses per minute. When pairing in the
      first component was eliminated, responding continued to be maintained in the
      second component. Elimination of food presentation from the first component
      substantially decreased responding in the second component, even though the brief
      stimulus had not been paired with food. Experiment II demonstrated that response
      rate was affected by the duration of both the second component and the brief
      stimulus. The results suggest that three conditions are important in maintaining
      responding with brief-stimulus presentations: (1) pairing the brief stimulus, at
      least initially, with food, (2) maintaining unconditioned reinforcement in one
      component, and (3) employing optimal brief-stimulus and component durations.

PMID- 16811956
TI  - Fixed versus variable sequences of food and stimulus presentation in second-order
      schedules.
AB  - Three pigeons were exposed to a second-order schedule in which the behavior
      specified by a fixed-interval component schedule was reinforced according to a
      ratio overall schedule. The completion of components not followed by food was
      signalled by a brief stimulus never paired with food. Food and the stimulus
      occurred in a random sequence or in fixed alternation, but the overall schedules
      (variable ratio 2 or fixed ratio 2) ensured that an equal number of food and
      brief-stimulus presentations occurred in each session. The control exerted by the
      food and by the brief stimulus was measured by overall response rates, mean
      pauses, frequency distributions of pauses, and response patterning across
      components. In general, the stimulus controlled patterns of behavior more similar
      to those controlled by food when food and the stimulus occurred in a random
      sequence than when they occurred in fixed alternation.

PMID- 16811957
TI  - Food deliveries during the pause on fixed-interval schedules.
AB  - Pigeons were trained on fixed-interval schedules of food delivery. In Experiments
      I and II, the fixed interval was initiated by the previous fixed-interval
      reinforcer; in Experiment III, the fixed interval was initiated by the first key
      peck following the preceding fixed-interval reinforcer (a chain fixed-ratio one,
      fixed-interval schedule). During the postreinforcement pause, variable-time
      schedules delivered food independent of any specific response. Rate of food
      delivery during the pause had only small effects on pause duration in Experiments
      I and II. In Experiment III, however, pause duration increased systematically
      with the rate of food delivery during the pause. These data suggest that the
      momentary proximity to reinforcement delivered via the fixed-interval schedule
      exerts potent control over pause termination. Additional analysis revealed that
      pause termination was unaffected by the intermittent delivery of food during the
      pause. Such data suggest that the temporal control by fixed-interval schedules is
      highly resistant to interference.

PMID- 16811958
TI  - Local contrast and Pavlovian induction.
AB  - Two experiments examined the effects of number and similarity of stimuli on local
      contrast. In the first experiment, local contrast effects differed in magnitude
      as a function of the similarity among stimuli; greater positive local contrast
      appeared when stimuli were less similar, though this effect sometimes reversed
      for very dissimilar stimuli. In the second experiment, both positive and negative
      local contrast appeared transiently during the course of training a
      discrimination including two quite dissimilar stimuli. When two new stimuli were
      added, both effects reappeared in several cases. The effects remained when the
      discrimination was rendered more difficult by substituting a new stimulus very
      similar to one of the original pair. These and other data suggest that local
      contrast depends on the same factors that produce Pavlovian induction; in the
      absence of an alternative account, Pavlov's interpretation may be useful in
      suggesting further research that will help identify the mechanisms involved in
      both classical and operant discrimination learning.

PMID- 16811959
TI  - The effects of unsignalled delayed reinforcement.
AB  - Pigeons' pecks were reinforced according to a variable-interval schedule. A delay
      of-reinforcement procedure was then added to the schedule, or a yoked-control
      procedure was arranged where the reinforcers occurred independently of responding
      according to the same variable-interval schedule. During the delay-of
      reinforcement procedure, the first peck after a reinforcer was scheduled began a
      delay timer and the reinforcer was delivered at the end of the interval. No
      stimulus change signalled the delay interval and responses could occur during it,
      so that the obtained delays were often shorter than those scheduled. Responding
      under this procedure was highly variable but, in general, behavior was
      substantially reduced even with the shortest delay used, 3 sec. In addition, the
      rates maintained by delayed reinforcement were only slightly greater than those
      maintained by the yoked-control procedure, suggesting that adventitious pairings
      of response and reinforcer were responsible for some of the maintenance of
      behavior that did occur. The results challenge recent conceptions of
      reinforcement as involving response-reinforcer correlations and re-emphasize the
      role of temporal proximity between response and reinforcer.

PMID- 16811960
TI  - Autoshaping, random control, and omission training in the rat.
AB  - The role of the stimulus-reinforcer contingency in the development and
      maintenance of lever contact responding was studied in hooded rats. In Experiment
      I, three groups of experimentally naive rats were trained either on autoshaping,
      omission training, or a random-control procedure. Subjects trained by the
      autoshaping procedure responded more consistently than did either random-control
      or omission-trained subjects. The probability of at least one lever contact per
      trial was slightly higher in subjects trained by the omission procedure than by
      the random-control procedure. However, these differences were not maintained
      during extended training, nor were they evident in total lever-contact
      frequencies. When omission and random-control subjects were switched to the
      autoshaping condition, lever contacts increased in all animals, but a pronounced
      retardation was observed in omission subjects relative to the random-control
      subjects. In addition, subjects originally exposed to the random-control
      procedure, and later switched to autoshaping, acquired more rapidly than naive
      subjects that were exposed only on the autoshaping procedure. In Experiment II,
      subjects originally trained by an autoshaping procedure were exposed either to an
      omission, a random-control, or an extinction procedure. No differences were
      observed among the groups either in the rate at which lever contacts decreased or
      in the frequency of lever contacts at the end of training. These data implicate
      prior experience in the interpretation of omission-training effects and suggest
      limitations in the influence of stimulus-reinforcer relations in autoshaping.

PMID- 16811961
TI  - Autoshaping as a function of prior food presentations.
AB  - Young chickens were given 1, 10, 100, or 1000 presentations of grain in a hopper.
      Subsequently, the key was illuminated before each presentation of grain to study
      autoshaping of the key-peck response. The number of keylight-grain pairings
      before a bird first pecked the lighted key was found to be a U-shaped function of
      the number of prior food-only presentations, with pecks occurring significantly
      sooner after 100 food-only trials than after any of the other values. Two of five
      chicks at the 100-trial value pecked on the first illumination of the key.
      Experiment II showed further that when a series of food-only trials (no keylight)
      preceded keylight-only trials (no food) 30% of the chicks pecked the illuminated
      key. Experiment III extended the generality of first-trial pecking to pigeons.
      After preliminary training with food-only, two of five pigeons pecked on the
      first illumination of a key. The results suggest a close relationship between
      autoshaping and pseudo-conditioning.

PMID- 16811962
TI  - Reinforcement rate and interresponse time differentiation.
AB  - Reinforcement rate and differential reinforcement of IRTs were independently
      manipulated to assess their relative contribution to the control of interresponse
      times (IRTs). Modified percentile reinforcement schedules (Platt, 1973) allowed
      control of reinforcement rate while longest or shortest IRTs were selectively
      reinforced. In the absence of differential IRT reinforcement, mean IRT decreased
      with increasing reinforcement rate. Compared to this small effect of
      reinforcement rate, reinforcement of long IRTs produced large changes in mean IRT
      at constant reinforcement rates. No interaction of reinforcement rate and IRT
      reinforcement was detected. The demonstration of large IRT changes in the absence
      of reinforcement-rate changes indicates the precedence of IRT reinforcement over
      molar reinforcement-rate correlations in the determination of IRTs in these
      procedures.

PMID- 16811963
TI  - Short-term memory in the pigeon: the previously reinforced response.
AB  - Eighteen pigeons served in a discrete-trials short-term memory experiment in
      which the reinforcement probability for a peck on one of two keys depended on the
      response reinforced on the previous trial: either the probability of
      reinforcement on a trial was 0.8 for the same response reinforced on the previous
      trial and was 0.2 for the other response (Group A), or, it was 0 or 0.2 for the
      same response and 1.0 or 0.8 for the other response (Group B). A correction
      procedure ensured that over all trials reinforcement was distributed equally
      across the left and right keys. The optimal strategy was either a winstay, lose
      shift strategy (Group A) or a win-shift, lose-stay strategy (Group B). The
      retention interval, that is the intertrial interval, was varied. The average
      probability of choosing the optimal alternative reinforced 80% of the time was
      0.96, 0.84, and 0.74 after delays of 2.5, 4.0, and 6.0 sec, respectively for
      Group A, and was 0.87, 0.81, and 0.55 after delays of 2.5, 4.0, and 6.0 sec,
      respectively, for Group B. This outcome is consistent with the view that behavior
      approximated the optimal response strategy but only to an extent permitted by a
      subject's short-term memory for the cue correlated with reinforcement, that is,
      its own most-recently reinforced response. More generally, this result is
      consistent with "molecular" analyses of operant behavior, but is inconsistent
      with traditional "molar" analyses holding that fundamental controlling relations
      may be discovered by routinely averaging over different local reinforcement
      contingencies. In the present experiment, the molar results were byproducts of
      local reinforcement contingencies involving an organism's own recent behavior.

PMID- 16811964
TI  - Effects of concurrent response-independent reinforcement on fixed-interval
      schedule performance.
AB  - In three experiments, behavior maintained by fixed-interval schedules changed
      when response-independent reinforcement was delivered concurrently according to
      fixed- or variable-time schedules. In Experiment I, a pattern of positively
      accelerated responding during fixed interval was changed to a linear pattern when
      response-independent reinforcement occurred under a variable-time schedule.
      Overall response rates (total responses/total time) decreased as the frequency of
      response-independent reinforcement increased. Experiment II showed that the
      response-rate changes in the first experiment were controlled by the response
      reinforcer relation, but the changes in patterns of responding were similar
      whether concurrently available reinforcement at varying times was response
      dependent or response-independent. In the final experiment, the addition of
      response-independent reinforcement at fixed times to a fixed-interval schedule
      resulted in changes in both local and overall response rates and in the
      occurrence of positively accelerated responding between reinforcements. These
      results suggest that the temporal distribution of reinforcers determines response
      patterns and that both the response-reinforcement dependency and the schedule of
      reinforcement determine overall response rates during concurrently scheduled
      response-dependent and response-independent reinforcement.

PMID- 16811966
TI  - Aversive control by an electrostatic shock source: an unmodifiable, humane
      preparation.

PMID- 16811967
TI  - Editorial.

PMID- 16811965
TI  - Conjunctive schedules of response-dependent and response-independent
      reinforcement.
AB  - Pigeons received food when they emitted the number of responses specified by a
      fixed-ratio schedule, and the time specified by a fixed-time schedule had
      elapsed. The order of meeting the response and time requirements was irrelevant.
      In different conditions, stimuli signalled completion of one, both, or neither
      requirement. Ratio size interacted with stimulus condition to determine
      performance. When a stimulus signalled the end of the fixed-time period, under
      all ratios the birds tended to respond after the stimulus appeared. When stimuli
      followed both components, small ratios produced responding during the fixed-time
      period, and other ratios resulted in responses after the time period had elapsed.
      With either no stimulus changes, or with a stimulus correlated with completion of
      the ratio alone, responding first increased and then decreased as the ratio
      increased. Low and high ratios produced stable response frequencies and patterns
      in successive intervals. Intermediate ratios resulted in two types of
      performance. Intervals with long initial pauses and few responses during the
      fixed-time period were followed by intervals with short pauses and numerous
      responses and vice versa. The source of these dynamic effects was hypothesized to
      be number of responses per reinforcer in one condition and response-reinforcer
      contiguity in the other.

PMID- 16811968
TI  - Behaviors observed during S- in a simple discrimination learning task.
AB  - Key pecking of pigeons was reinforced with food in the presence of a horizontal
      line and never reinforced in the presence of a vertical line. Highly stereotyped
      behaviors, as well as key pecking, were observed and recorded in the presence of
      both stimuli. Results showed that a high proportion of time spent in the presence
      of the horizontal line was occupied by key pecking, a high proportion of time in
      the presence of the vertical line was occupied by stereotyped nonkey-pecking
      behaviors, and intermediate proportions of time spent in the presence of
      intermediate stimuli were occupied by each class of behavior during
      generalization tests. Similar running rates (number of key pecks divided by
      observed key-pecking time) were obtained in the presence of all stimuli,
      indicating that changes in time rather than tempo accounted for the changes in
      overall rates of key pecking. An exception occurred in responding to the
      horizontal line as differential performance was developing. In addition to an
      increase in time spent key pecking, increased running rates occurred in seven of
      eight birds, suggesting that both time allocation and tempo play a role in
      behavioral contrast of overall rates of key pecking.

PMID- 16811969
TI  - Dependency, temporal contiguity, and response-independent reinforcement.
AB  - A comparison was made of the effects of variable-interval, variable-time, and
      tandem variable-interval fixed-time schedules on key-peck responding of pigeons.
      The variable-interval component of the tandem schedule retained the response
      reinforcement dependency; the fixed-time component allowed the temporal proximity
      between responding and reinforcement to vary, constrained only by the duration of
      the fixed-time interval. Response rates were highest during the variable-interval
      and lowest during the variable-time schedule. Intermediate response rates
      occurred during the tandem schedule. The results of a yoked control condition
      showed that the effects of the tandem schedule were not due simply to changes in
      reinforcement distribution or frequency. The results suggest that substantial
      reductions in responding occur when reinforcement is response-dependent but not
      necessarily contiguous with the response required to produce reinforcement.

PMID- 16811970
TI  - Social learning by following: an analysis.
AB  - Learning by "following", probably a common means by which behaviors are socially
      transmitted from adults to young in many species, was analyzed. Pigeons first
      learned to eat from a human hand. When the hand then approached an operant key
      and pecked it, the pigeons followed and quickly learned to do the same, thereby
      demonstrating social learning. When the hand only led the birds to the area of
      the key, without demonstrating the key-peck response, the birds learned as
      rapidly as with a key-peck demonstration. Birds also learned, but less reliably
      and more slowly, when they could observe the hand's responses but were
      constrained and unable to follow. "Following" was also shown to engender very
      rapid learning of a more complex, two-member response chain.

PMID- 16811971
TI  - Quantitative studies of reinforcement relativity.
AB  - Three experiments examined an application of the matching law to the area of
      reinforcement relativity. In Experiment I, rats ran in a wheel and drank a
      sucrose solution. Equations derived from the matching law made fairly accurate
      predictions of the amounts of time spent running and drinking when licks and
      wheel revolutions had to occur in fixed proportions. In Experiment II, rats were
      required to spend four times as much time drinking as running, but the absolute
      durations of the cycles of drinking and running were varied. Except for the
      shortest cycle size tested, durations were close to those predicted. Experiments
      III investigated a tendency for obtained durations of running and drinking to be
      slightly longer than predicted. Simply shortening the periods when these
      behaviors were available increased their values. It was concluded that the
      matching law equations provided reasonably accurate predictions in some
      experiments, but changes in motivation set the limits of such accuracy.

PMID- 16811972
TI  - Line-orientation generalization following signalled-reinforcer training.
AB  - Three naive and three nonnaive pigeons key pecked for food on a multiple variable
      interval 1-minute variable-interval 1-minute schedule with a black zero-degree
      vertical line on a white surround associated with one component and a black line
      shifted 30 degrees to the right (+30 degree) associated with the other component.
      Subsequently, a signalled-reinforcer procedure was introduced in the +30 degree
      component, i.e., whenever the reinforcer was available for the next response, the
      key changed to blank white. Following this training, the original unsignalled
      reinforcer condition was re-instated. Line orientation generalization tests were
      given at the end of signalled-reinforcer training and after the second
      unsignalled-reinforcer condition. The signalled-reinforcer procedure reduced
      response rate in the +30-degree component in all subjects but facilitated
      responding during the zero-degree component (behavioral contrast) for two of the
      naive subjects only. However, average generalization gradients following
      signalled-reinforcer training indicated peak shift in two subjects and area shift
      in all five subjects that completed the experiment. There was no apparent
      relation between contrast and peak shift or degree of area shift. The data were
      interpreted as supporting the notion that the signalled-reinforcer procedure
      segments a variable-interval schedule into extinction and fixed ratio 1 segments.

PMID- 16811973
TI  - Response summation to a compound stimulus in a context of choice.
AB  - Key pecks by two groups of pigeons were reinforced on concurrent schedules. For
      group E, pecks were reinforced during either a visual or an auditory stimulus;
      for group E, an additional, extinction component was available, during which both
      visual and auditory stimuli were absent. After training, both groups were given a
      compound test to measure preference among four stimuli, the three used in
      training plus a compound of the visual and auditory stimulus. Group E showed
      preference for the compound, emitting more pecks and spending more time in this
      stimulus than in other stimuli. Group E showed no preference between the compound
      and visual stimulus, nor between the auditory stimulus and the absence of both
      stimuli, but preferred the former pair over the latter pair of stimuli.

PMID- 16811974
TI  - Matching under concurrent fixed-ratio variable-interval schedules of food
      presentation.
AB  - Four pigeons were exposed to concurrent fixed-ratio, variable-interval schedules
      of food presentation. The fixed-ratio requirement was either 25, 50, 75, or 100
      responses, with the variable-interval schedule parameter held constant at 4
      minutes. A delay time was imposed between a changeover from one schedule to the
      other and subsequent food availability. The delay time was varied at each ratio
      requirement over four values; no delay, 0-second delay, 1.5-second delay, and 5.0
      second delay. As the fixed-ratio requirement or the delay time increased, a
      greater proportion of the total responses and time spent responding occurred
      under the variable-interval schedule relative to the proportion of food
      deliveries under that schedule. Neither relative overall response rate nor
      relative time spent responding equalled the relative frequency of food
      presentation, as would be predicted by a linear "matching" model. Rather, these
      data were described by power functions with slopes of approximately 1.0 and
      intercepts greater than 1.0. In the terms of Baum's (1974) analysis, these
      deviations from linear matching represent bias in favor of responding under the
      interval schedule. Bias, as reflected in the intercept of the power function, was
      greater for the ratio of time than the ratio of responses.

PMID- 16811975
TI  - The matching law in and within groups of rats.
AB  - In each of the two experiments, a group of five rats lived in a complex maze
      containing four small single-lever operant chambers. In two of these chambers,
      food was available on variable-interval schedules of reinforcement. In Experiment
      I, nine combinations of variable intervals were used, and the aggregate lever
      pressing rates (by the five rats together) were studied. The log ratio of the
      rates in the two chambers was linearly related to the log ratio of the
      reinforcement rates in them; this is an instance of Herrnstein's matching law, as
      generalized by Baum. Summing over the two food chambers, food consumption
      decreased, and response output increased, as the time required to earn each
      pellet increased. In Experiment II, the behavior of individual rats was observed
      by time-sampling on selected days, while different variable-interval schedules
      were arranged in the two chambers where food was available. Individual lever
      pressing rates for the rats were obtained, and their median bore the same
      "matching" relationship to the reinforcement rates as the group aggregate in
      Experiment I. There were differences between the rats in their distribution of
      time and responses between the two food chambers; these differences were
      correlated with differences in the proportions of reinforcements the rats
      obtained from each chamber.

PMID- 16811976
TI  - Transfer of oddity-from-sample performance in pigeons.
AB  - Four pigeons were trained on a modified three-key oddity-from-sample task in
      which an observing response to the sample (center-key) stimulus lighted a single
      comparison (side-key) stimulus. If the comparison stimulus was different from the
      sample stimulus, a single peck to the lighted comparison was reinforced. If the
      comparison and sample stimuli were identical, the pigeons had to refrain from
      pecking the comparison for 4.6 seconds to terminate the matching comparison and
      to produce immediately a nonmatching comparison on the remaining side key. Each
      peck to the matching comparison reset the 4.6-second delay interval. Three hues
      were used during acquisition. During tests for transfer of the oddity
      performance, two novel hues were substituted either individually or together for
      one or two of the original training hues. For three birds, latencies to novel
      nonmatching hues were identical to baseline nonmatching latencies. Latencies to
      novel matching hues were shorter than baseline matching latencies but were
      consistently longer than novel nonmatching latencies. These transfer data
      demonstrate that the pigeons learned the oddity concept.

PMID- 16811977
TI  - Undermatching: a reappraisal of performance on concurrent variable-interval
      schedules of reinforcement.
AB  - The extant data for pigeons' performance on concurrent variable-interval
      schedules were examined in detail. Least-squares lines relating relative pecks
      and time to the corresponding relative reinforcements were obtained for four
      studies. The between-study group slopes for time and pecks and five of seven
      within-study group slopes from individual studies were less than 1.00. This
      suggested the generality that pigeons respond less to the richer reinforcement
      schedule than predicted by matching. For pecks, a nonparametric test for
      distribution of points also supported this concept of undermatching (to the
      richer reinforcement schedule). In addition, using mean squared error as the
      criterion, a cubic curve fit the peck proportion data better than any line or
      other polynomial. This indicates that the relation between peck and reinforcement
      proportions may be nonlinear.

PMID- 16811978
TI  - The application of the matching law to simple ratio schedules.

PMID- 16811979
TI  - Elimination of reinforced behavior: intermittent schedules of not-responding.
AB  - Pigeons' key pecking resulted in food according to either a variable-ratio or a
      variable-interval schedule. At the same time, food was available for not pecking
      for a specified time. The required time of not-pecking was segmented into not
      responding units, and these units were followed by food according to a fixed
      ratio schedule. Both unit duration and the number required were varied. In
      general, the shorter the time unit or the smaller the ratio, the lower was
      response rate. When total required not-responding time was constant, but changes
      in unit duration and the number required altered how the total was achieved,
      shorter units produced lower rates. Other conditions involved substitution of
      food delivered independent of responding for the not-responding schedule. With
      low and moderate total times to food presentation, the not-responding schedule
      produced lower rates; with the longest times, the response-independent schedule
      generated less responding. When considered in terms of relative frequency of food
      presentation available from a source other than pecking, the not-responding
      schedule reduced rate more effectively than did the response-independent
      schedule. Comparisons with other research suggested that food presented dependent
      on not responding compared favorably with punishment as a procedure for reducing
      response rate. Transient effects differed. Although punishment temporarily
      depresses rate when first imposed and temporarily enhances it when first removed,
      food given for not responding quickly generated steady-state rates.

PMID- 16811980
TI  - Behavioral adaptation to fixed-interval and fixed-time food delivery in golden
      hamsters.
AB  - Food-deprived golden hamsters in a large enclosure received food every 30 sec
      contingent on lever pressing, or free while their behavior was continuously
      recorded in terms of an exhaustive classification of motor patterns. As with
      other species in other situations, behavior became organized into two main
      classes. One (terminal behaviors) increased in probability throughout interfood
      intervals; the other (interim behaviors) peaked earlier in interfood intervals.
      Which class an activity belonged to was independent of whether food was
      contingent on lever pressing. When food was omitted on some of the intervals
      (thwarting), the terminal activities began sooner in the next interval, and
      different interim activities changed in different ways. The interim activities
      did not appear to be schedule-induced in the usual sense. Rather, the hamsters
      left the area of the feeder when food was not due and engaged in activities they
      would normally perform in the experimental environment.

PMID- 16811981
TI  - Response and time allocation in concurrent second-order schedules.
AB  - Six pigeons were trained on two-key concurrent variable-interval schedules in
      which the required response was the completion of a fixed number of key pecks.
      When the required number of pecks was equal on the two keys, response- and time
      allocation ratios under-matched obtained reinforcement rate ratios. A similar
      result was found when the required number of pecks was unequal, except that
      performance, measured in response terms, was biased to the shorter required
      number of pecks and was less sensitive to reinforcement-rate changes. No such
      differences were found in the data on time spent responding. When the variable
      interval schedules were kept constant and the required numbers of pecks were
      systematically varied, response ratios changed inversely with the ratio of the
      required number of pecks, but time-allocation ratios varied directly with the
      same independent variable. Thus, on response measures, pigeons "prefer" the
      schedule with the smaller peck requirement, but on time measures they "prefer"
      the schedule with the larger peck requirement. This finding is inconsistent with
      a commonsense notion of choice, which sees response and time-allocation measures
      as equivalent.

PMID- 16811983
TI  - Concurrent schedules: a quantitative relation between changeover behavior and its
      consequences.
AB  - Data from several published experiments on concurrent variable-interval schedules
      were analyzed with respect to the effects of changeover delay on the time spent
      responding on a schedule before changing to an alternate schedule: i.e., the
      interchangeover time. Interchangeover time increases as the duration of the
      changeover delay increases, and the present analysis shows that a power function
      describes the relation. The power relation applied in spite of numerous
      differences in the experiments: different variable-interval schedules for the
      concurrent pairs; equal or unequal reinforcement rates for the schedules of the
      concurrent pairs; different durations of the changeover delay; response-dependent
      or response-independent reinforcers; pigeons or rats as subjects; different
      reinforcers. A power function also described the data in experiments where the
      changeover incurred a timeout, where a fixed ratio was required to changeover,
      and also when asymmetrical changeover delays were used.

PMID- 16811982
TI  - Signalled and unsignalled percentage reinforcement of performance under a chained
      schedule.
AB  - Pigeons were trained to peck a key under a chained fixed-ratio 15 fixed-interval
      25-sec schedule of food presentation. In Experiment 1, blocks of sessions in
      which 100%, 75%, 50%, and 25% of the sequences ended with food presentation were
      conducted. When food presentation was omitted, a timeout of equal duration
      replaced it. As the frequency of food presentation decreased so did the frequency
      of completing the chained schedule. In Experiment 2, 75%, 50%, or 25% of the
      sequences terminated with food presentation and outcomes were signalled, i.e.,
      completion of the fixed ratio resulted in either a stimulus correlated with the
      fixed-interval 25-sec schedule or a stimulus correlated with extinction. As the
      frequency of food presentation decreased, the number of sequences completed per
      session increased for two pigeons and remained high for a third. In Experiments 3
      and 4, assessments of the effects of signalling the outcome of the chained
      schedule were made with response-independent presentation of events at the end of
      the sequence. Again, signalling the outcome of the chained schedule led to more
      chains being completed per session than did not signalling the outcome. Stimuli
      differentially paired with food presentation have powerful behavioral effects
      that may be attributed to the potency of these stimuli as conditioned
      reinforcers.

PMID- 16811984
TI  - Effects of fixed-ratio sample and choice response requirements upon oddity
      matching.
AB  - Three pigeons were trained on oddity matching in which either 1, 4, 8, 16, or 32
      sample-key observing responses were required to turn off the sample stimuli and
      turn on the comparison stimuli. Oddity accuracy increased when the observing
      response requirement was raised and decreased when the requirement was lowered.
      Next, while the observing requirement was maintained at one response, the number
      of responses required to the comparison stimuli was either 1, 4, 8, 16, or 32.
      Under these conditions, choice was defined as the comparison that first
      accumulated the required number of responses. In general, increasing the
      comparison-response requirement decreased accuracy and lowering the comparison
      requirement increased accuracy. The fixed-ratio observing requirements appeared
      to facilitate control by stimuli serving an instructional function.

PMID- 16811985
TI  - Positive contrast, negative induction, and inhibitory stimulus control in the
      rat.
AB  - In Experiment I, 24 rats were trained on a multiple variable-interval variable
      interval schedule with a doorlight and white noise serving as component cues. Two
      groups were then shifted to a multiple extinction variable-interval schedule, and
      a third group was maintained on the multiple variable-interval variable-interval
      schedule. The multiple extinction variable-interval condition produced positive
      contrast when either the light or noise signalled extinction, and both of these
      cues acquired inhibitory stimulus control as measured by a combined cue test. In
      Experiment II, the multiple variable-interval variable-interval condition was
      shifted to multiple extinction variable-interval for one group, to multiple
      variable-time variable-interval for a second group, and was unchanged for the
      third group. The two experimental conditions produced identical patterns of
      response-rate reduction in the altered component, but the multiple extinction
      variable-interval condition produced positive contrast, whereas the multiple
      variable-time variable-interval condition did not. Subsequent combined cue and
      resistance to reinforcement tests revealed that the cue signalling extinction
      acquired stronger inhibitory stimulus control than the cue signalling variable
      time.

PMID- 16811986
TI  - Time limits for completing fixed ratios. IV. Components of the ratio.
AB  - Pigeons received food after completing a fixed ratio if the temporal properties
      of responding exceeded minimum duration requirements. In one set of conditions, a
      minimum time had to elapse before the first response of the ratio (the initial
      pause). In another set, the minimum duration was the time between the first and
      last response of the ratio. Obtained times increased as a power function of
      required times in both conditions. The power function resembled that occurring in
      experiments involving temporal differentiation of individual responses,
      interresponse times, latencies, and entire fixed-ratio sequences. Moreover, in
      all of these experiments individual performances could be described as a function
      of the base duration (the duration occurring in the absence of temporal
      requirements) and the specific time requirement. Control conditions indicated
      that the effects resulted from temporal requirements and not from reinforcer
      intermittency.

PMID- 16811987
TI  - General attentiveness effects of discriminative training.
AB  - Using a design that permitted the simultaneous assessment of intra-, inter-, and
      extradimensional effects of discriminative training, the generality of
      discriminative effects that have been said to reflect increases in "general
      attentiveness" was assessed. Pigeons received either discriminative training with
      two stimuli correlated with reinforcement and one stimulus correlated with
      nonreinforcement, or nondifferential reinforcement (control) training. One
      positive stimulus was part of an intradimensional task and the other was not.
      After training, generalization tests were conducted to assess stimulus control
      along several dimensions. Discriminative training resulted in increased control
      along dimensions of the positive stimulus involved in the intradimensional task,
      but not along any dimensions of the other positive stimulus. The results
      suggested that discriminative training leads to increases in attention that are
      neither so general as suggested by the "general attentiveness" view nor so
      specific as to be revealed solely by intradimensional effects.

PMID- 16811988
TI  - Pigeons' preferences for stimulus information: effects of amount of information.
AB  - A concurrent-chain procedure was used to study pigeons' preferences as a function
      of amount of information. Pigeons chose between two terminal links. Both terminal
      links ended in food reinforcement with probability (p) and in blackout with
      probability (1-p). One terminal link (noninformative link) was signalled by a
      stimulus uncorrelated with either food or blackout. The other terminal link
      (informative link) was signalled by stimuli correlated with these outcomes.
      Amount of information conveyed by these stimuli was varied across conditions by
      changing the probability of reinforcement (p) and blackout (1-p). The pigeons
      strongly preferred the informative link, and preferences were greater at p values
      above 0.50 than for their complements. The pigeons engaged in different behaviors
      during the stimulus periods, suggesting that the value of informative stimuli may
      be in their function as discriminative stimuli for interim activities and
      terminal responses.

PMID- 16811989
TI  - Effect of punishment on human variable-interval performance.
AB  - Three female human subjects pressed a button for monetary reinforcement in a
      range of variable-interval schedules specifying different frequencies of
      reinforcement. On alternate days, responding was also punished (by subtracting
      money) according to a variable-ratio 34 schedule. In the absence of punishment,
      rate of responding was an increasing negatively accelerated function of
      reinforcement frequency; the relationship between response rate and reinforcement
      frequency conformed to Herrnstein's equation. The effect of the punishment
      schedule was to suppress responding at all frequencies of reinforcement. This was
      reflected in a change in the values of both constants in Herrnstein's equation:
      the value of the theoretical maximum response-rate parameter was reduced, while
      the parameter describing the reinforcement frequency corresponding to the half
      maximal response rate was increased.

PMID- 16811990
TI  - Signalled free-operant avoidance of shock by pigeons pecking a key.
AB  - Two pigeons were trained to peck a key under a free-operant avoidance schedule.
      Then, changes in key color signalled the beginning (safe period) and the end
      (warning period) of the response-shock interval, with a response required to
      change the key color. Finally, a change in key color signalled the warning period
      and either a response or a shock reinstated the safe stimulus. During signalled
      avoidance, response rate was higher during the warning stimulus than during the
      safe stimulus. More responding tended to occur in the warning stimulus when it
      was terminated by either a response or a shock than by only a response. In either
      procedure, response latency during the warning stimulus was a function of the
      duration of the warning stimulus. In general, response and shock rate were higher
      during unsignalled than during signalled avoidance. When the warning stimulus was
      brief, the results were similar to those of unsignalled avoidance. These results
      confirm previous findings with pigeons, are in general agreement with data
      provided by other species in studies of signalled avoidance, and thereby indicate
      the transituationality of the key-pecking operant.

PMID- 16811992
TI  - Studies of operant and reflexive key pecks in the pigeon.
AB  - The duration of pigeons' key pecks was studied in three experiments. Experiment I
      revealed that key pecks early in exposure to continuous reinforcement were of
      short duration, as were key pecks observed on an omission procedure in which
      pecks prevented food delivery. Key pecks later in exposure to continuous
      reinforcement, and those that occurred on positive automaintenance procedures,
      were of long duration. In Experiment II, pigeons were exposed to fixed-interval
      and fixed-ratio reinforcement schedules, and durations were recorded separately
      for each quarter of each interval or ratio. On fixed interval, durations were
      shorter in the first quarter of each interval than in subsequent quarters; on
      fixed ratio, durations were longer in the first quarter of the ratio than in
      subsequent quarters. These data parallel observations of concurrent operant
      responding and salivation in dogs. In Experiment III, pigeons were exposed to a
      discrete trial, differential-reinforcement-of-low-rate 6-sec schedule. Durations
      of responses in the first 2 sec of the trial were substantially shorter than
      those of responses that occurred later. The data from all three experiments
      support the view that the pigeon's "key peck" actually consists of two subclasses
      of peck, one reflexive and one operant.

PMID- 16811991
TI  - Control of pigeons' pecking by trace stimuli.
AB  - In Experiment I, pigeons' pecking a white key was reinforced with grain when
      white was immediately preceded by a vertical white line on a green surround, but
      not by green alone. This procedure produced control of pecking by the line. Next,
      pecking white was reinforced after vertical line on green, but not after green
      alone or other orientations of the white line on green. The line-tilt dimension
      initially did not control pecking, a result that showed that interdimensional
      (line versus no line) training does not always result in dimensional control.
      Line-tilt control was eventually established but was accompanied by a decrease in
      interdimensional control. In Experiment II, interdimensional training, with or
      without a trace interval intervening between line on green or green alone and
      white, was followed by tests for line-tilt control. While interdimensional
      control was unaffected by the trace interval, line-tilt control tended to be less
      with the trace interval. This dissociation of interdimensional and dimensional
      control, as well as the failure of interdimensional training to produce
      dimensional control in Experiment I, suggests that the line stimulus is
      multidimensional.

PMID- 16811993
TI  - The conditioned reinforcement of repeated acquisition.
AB  - Three monkeys were trained to emit a chain of three responses on three separate
      levers in a set of six levers to obtain food. The chain producing food (correct
      chain) was changed each day. During a trial, a press on any lever produced a
      feedback stimulus; a press on a correct lever produced an additional distinctive
      stimulus; the third correct press produced a food pellet. Test sessions in which
      either the food or the distinctive stimuli were removed were interspersed with
      baseline sessions. In tests without food presentations, the subjects acquired the
      correct chain rapidly, with a level of accuracy comparable to baseline. Removing
      the distintive stimuli for either the first or second member of the correct chain
      greatly retarded acquisition of that member of the chain. Removing all
      distinctive stimuli often reduced accuracy throughout the chain to chance level,
      even though food was presented following each correct chain. These results were
      interpreted as evidence that the distinctive stimuli presented after correct
      responses functioned as conditioned reinforcers. Reductions in accuracy following
      an omitted distinctive stimulus indicated that they were also discriminative
      stimuli for correct responding in their presence.

PMID- 16811994
TI  - Auditory stimulus control in pigeons: Jenkins and Harrison (1960) revisited.
AB  - Pigeons were trained to peck a key in the presence of a 1000-Hz tone on a
      variable-interval one-minute schedule of reinforcement. One group was trained
      with an illuminated key; the other was trained in a totally dark chamber. During
      a generalization test on tonal frequency, subjects trained and tested with the
      key illuminated produced rather shallow gradients around the training value;
      subjects trained and tested in the dark produced steeper generalization
      gradients. These data replicate Jenkins and Harrison's (1960) finding that tone
      acquires relatively little control over responding and demonstrate that this
      absence of control is a function of the presence of the keylight.

PMID- 16811995
TI  - Magnitudes of score differences produced within sessions in a cooperative
      exchange procedure.
AB  - Interest centered on maximal score differences produced within sessions during
      two-party exchange. Subjects chose between earning money independently or through
      potentially higher-paying exchange. In the exchange option, only one person could
      produce points for the other on a trial. Because each exchange response ("give")
      required the giver to forego earning points independently, the larger the score
      difference produced (i.e., the further ahead in earnings the other person was
      put), the greater the reduction in the giver's earnings if the other person did
      not reciprocate. Results showed that scores were usually equal at the end of each
      session, and that subjects maintained close equality of scores throughout each
      session. When a response-cost contingency that punished the alternation of giving
      was introduced, however, large within-session score differences developed. These
      large differences continued to be produced after the response-cost contingency
      was removed. Finally, when subjects were told that the session could end at any
      moment, score differences were sharply reduced, indicating that production of
      score differences remained under the control of discriminative stimuli associated
      with the likelihood of reciprocation. The study suggests that with appropriate
      procedures, an experimental analysis of behavioral phenomena associated with the
      concept of "trust" may be possible.

PMID- 16811996
TI  - Some implications of a relational principle of reinforcement.
AB  - A formal statement of a relational principle of reinforcement is developed that
      makes contact with analyses of choice, interresponse-time distributions, and
      stimulus control. Some implications for current theoretical and empirical work in
      the various areas are examined.

PMID- 16811997
TI  - The effect of reinforcement differences on choice and response distribution
      during stimulus compounding.
AB  - In Experiments I and II, rats were trained to respond on one lever during light
      and another during tone. The absence of tone and light controlled response
      cessation. In the multiple schedule of Experiment I, all reinforcements were
      received for responding in tone or light; in the chain schedule of Experiment II,
      all reinforcements were received in no tone + no light for not responding.
      Experiment I subjects, for which tone and light were associated with response and
      reinforcement increase, responded significantly more to tone-plus-light than to
      tone or light alone (additive summation). Experiment II subjects, for which tone
      and light were associated with response increase and reinforcement decrease,
      responded comparably to tone, light, and tone + light. Thus, additive summation
      was observed when stimulus-response and stimulus-reinforcer associations in tone
      and light were both positive, but not when they were conflicting. All subjects in
      both experiments responded predominantly on the light-correlated lever during
      tone + light, even when light intensity was reduced in testing. Furthermore, when
      a light was presented to a subject engaged in tone-associated responding, all
      subjects immediately switched the locus of responding to the light-correlated
      lever. No change in locus occurred when a tone was presented to a subject engaged
      in light-associated responding, irrespective of the stimulus-reinforcer
      association conditioned to tone. The light-lever preference in tone + light
      indicates that the heightened responding observed in Experiment I was not the
      summation of tone-associated behavior with light-associated behavior. Rather, it
      appears to be the result of a facilitation of one operant (light-associated
      responding) by the reinforcement-associated cue for the other.

PMID- 16811998
TI  - Conditional discrimination performance by pigeons on a response-independent
      procedure.
AB  - Pigeons were trained on a differential autoshaping procedure in which both
      components of two-stimulus sequences predicted delivery or nondelivery of food.
      All birds acquired the conditional discrimination. When the subjects were exposed
      to an extinction procedure, the stimuli maintained conditional control as long as
      the birds continued to peck the key. When a delay interval was imposed between
      the two components of a stimulus sequence using a titration procedure, the
      stimuli maintained conditional control up to delay values of 7 to 10 sec. These
      data are consistent with the view that the controlling stimuli in conditional
      discrimination situations are compounds of stimulus elements.

PMID- 16811999
TI  - Demand for food on fixed-ratio schedules as a function of the quality of
      concurrently available reinforcement.
AB  - Six rats lever pressed for food on concurrent fixed-ratio schedules, in a two
      compartment chamber. In one compartment, mixed diet pellets were delivered on
      fixed-ratio schedules of 1, 6, 11, and 16; in the other, either no food was
      delivered, or sucrose or mixed diet pellets were delivered on fixed-ratio 8. The
      number of pellets obtained in the first compartment declined as a function of
      fixed-ratio size in that compartment in all three conditions, but the decline was
      greatest overall with mixed diet pellets concurrently available in the other
      compartment, and least with no food concurrently available. The result is
      discussed in terms of economic demand theory, and is consistent with the
      prediction that elasticity of demand for a commodity (defined in operant terms as
      the ratio of the proportionate change in number of reinforcements per session to
      the proportionate change in fixed-ratio size) is greater the more substitutable
      for that commodity are any concurrently available commodities.

PMID- 16812000
TI  - Extending sequence-class membership with matching to sample.
AB  - Three normal adults were first trained to point sequentially to each member of
      several pairs of visual stimuli. This baseline training established one class of
      stimuli to which subjects responded first, and another class of stimuli to which
      they responded second. Then, in a matching-to-sample procedure, baseline-sequence
      stimuli served as samples and new visual stimuli served as comparisons. Subjects
      were trained to choose one group of new comparisons when the sample was a "first"
      stimulus from the sequence baseline, and to choose the other new comparison
      stimuli when the sample was a "second" from the sequence baseline. When the new
      stimuli were then presented as pairs in the posttest, two subjects pointed to
      them in sequences predictable on the basis of the stimulus-class membership
      established during matching to sample. The failure of one subject to demonstrate
      sequential transfer was shown to be a consequence of the failure of the matching
      to-sample procedure to establish stimulus classes. The production of sequences
      that were not directly trained suggested an empirical approach to the analysis of
      simple grammatical behavior.

PMID- 16812001
TI  - Two types of pigeon key pecking: suppression of long- but not short-duration key
      pecks by duration-dependent shock.
AB  - The key pecking of eight pigeons was maintained on a variable-interval 1-minute
      schedule of food reinforcement. Sometimes, all responses between 35 and 50
      milliseconds in duration produced a shock; sometimes, all responses between 10
      and 25 milliseconds produced a shock; sometimes, shocks were produced by pecks
      without regard to duration (nondifferential punishment), and sometimes shocks
      were delivered independently of responding. Punishment of 35- to 50-millisecond
      responses selectively suppressed those responses, while punishment of 10- to 25
      millisecond responses and nondifferential punishment suppressed responding
      overall but did not suppress responses of particular duration. Punishment of 35-
      to 50-millisecond responses suppressed key pecking slightly less than did
      nondifferential punishment. Punishment of 10- to 25-millisecond responses and
      response-independent shock produced roughly equal amounts of suppression,
      substantially less than the other punishment procedures. The data support the
      view that there are at least two kinds of key peck, identifiable on the basis of
      duration, one of which (short duration) is insensitive to its consequences.

PMID- 16812002
TI  - Rate and temporal pattern of key pecking under autoshaping and omission schedules
      of reinforcement.
AB  - The role of response-reinforcer contiguity on autoshaped key pecking in pigeons
      was studied by scheduling response-dependent nonreinforcement at the beginning or
      the end of brief (8-sec) discrete trials. Schedules that permitted chance
      conjunctions of key pecking and food sustained high rates of responding, whereas
      those that prevented the occurrence of key peck-food intervals shorter than 4 sec
      sustained low response rates. In addition, selective reinforcement schedules
      supported accelerating or decelerating rates of responding within individual
      trials. These effects were traceable to response-reinforcer (operant), but not
      stimulus-reinforcer (respondent) factors.

PMID- 16812003
TI  - Punishment of autoshaped key-peck responses of pigeons.
AB  - The effects of different voltages of response-dependent and response-independent
      electric shock on the frequency of key-peck responses engendered by an
      autoshaping procedure were studied. In Experiments I and II, each response
      produced a brief electric shock, and response frequency generally decreased more
      with higher-voltage shock. Preshock frequencies of responding were generally
      recovered across successive sessions of relatively low-voltage shock delivery but
      not at higher shock voltages. The effects of response-dependent and response
      independent shock were compared in Experiment III by using a yoked-control
      procedure in which each pigeon received each type of shock delivery at different
      times. Response-dependent shock generally produced greater decreases in response
      frequency. In the final experiment, one response-independent shock per
      autoshaping trial was scheduled. The number of autoshaped responses per trial was
      related to shock voltages. These results suggest that response-dependent and
      response-independent electric shock effectively decrease frequency of autoshaped
      responses.

PMID- 16812004
TI  - Schedule-induced biting under fixed-interval schedules of food or electric-shock
      presentation.
AB  - Squirrel monkeys pressed a lever under fixed-interval schedules of food or of
      electric-shock presentation. Both schedules induced repeated biting on a latex
      hose. Whether lever pressing was controlled by food or by electric shock, a
      pattern of decreasing hose biting and increasing lever pressing occurred within
      fixed-interval cycles. As the fixed-interval duration was increased from 6 to 600
      sec, average rates of lever pressing decreased under both schedules. Average
      rates of hose biting first increased with increasing parameter value, reaching a
      maximum at values that varied from 60 to 337 sec in different monkeys, and then
      declined at higher values. d-Amphetamine at appropriate doses increased overall
      rates of lever pressing maintained by food or by shock, but either did not affect
      or decreased overall rates of hose biting. When no timeout period occurred
      between fixed-interval cycles, the monkeys bit most frequently immediately after
      food or electric shock was presented. When there was a timeout period, hose
      biting began shortly after the start of the fixed-interval cycles, with little or
      no hose biting immediately after food or electric shock was presented. Most hose
      biting appeared to be schedule-induced rather than food- or shock-induced.

PMID- 16812005
TI  - Selective punishment early and late in fixed-ratio schedules of food
      reinforcement.
AB  - Pigeons key pecked for grain on a fixed-ratio 100 schedule; electric shocks
      occurred intermittently at the fifteenth or eighty-fifth response in the ratio.
      In Experiment I, shock was at the fifteenth response for two birds, and at the
      eighty-fifth response for two others, in every sixth, twelfth, or eighteenth
      ratio. Rate of responding decreased as frequency of shock increased, and the
      pattern of responding included an increased initial pause and low rates or pause
      run sequences that extended further into the ratio when shock was at the
      fifteenth response than when it was at the eighty-fifth response. Shock early in
      the ratio engendered longer initial pauses than shock late in the ratio. In
      Experiment II, four birds responded on a two-component multiple schedule in which
      shock occurred at the fifteenth response of the third ratio in the presence of a
      white keylight and at the eighty-fifth response of the third ratio in the
      presence of a green keylight. The overall rates of responding decreased as shock
      intensity increased. All four birds responded differentially to the white and
      green keylights, but with a pattern that varied between birds. In general,
      punishment reduced the probability of responses that preceded it, regardless of
      the ordinal position of those responses. Both studies confirm that the
      probability of responding is reduced less by aversive stimuli produced late in a
      fixed-ratio than by aversive stimuli produced early in a fixed-ratio.

PMID- 16812006
TI  - Uninstructed human responding: sensitivity to ratio and interval contingencies.
AB  - College students' presses on a telegraph key were occasionally reinforced by
      light onsets in the presence of which button presses (consummatory responses)
      produced points later exchangeable for money. One student's key presses were
      reinforced according to a variable-ratio schedule; key presses of another student
      in a separate room were reinforced according to a variable-interval schedule
      yoked to the interreinforcement intervals produced by the first student.
      Instructions described the operation of the reinforcement button, but did not
      mention the telegraph key; instead, key pressing was established by shaping.
      Performances were comparable to those of infrahuman organisms: variable-ratio key
      pressing rates were higher than yoked variable-interval rates. With some yoked
      pairs, schedule effects occurred so rapidly that rate reversals produced by
      schedule reversals were demonstrable within one session. But sensitivity to these
      contingencies was not reliably obtained with other pairs for whom an experimenter
      demonstrated key pressing or for whom the reinforcer included automatic point
      deliveries instead of points produced by button presses. A second experiment with
      uninstructed responding demonstrated sensitivity to fixed-interval contingencies.
      These findings clarify prior failures to demonstrate human sensitivity to
      schedule contingencies: human responding is maximally sensitive to these
      contingencies when instructions are minimized and the reinforcer requires a
      consummatory response.

PMID- 16812007
TI  - Stimulus generalization from feeder to response key in the acquisition of
      autoshaped pecking.
AB  - During autoshaping, a 6-second presentation of one stimulus and a variable time
      30-second presentation of a second stimulus alternated in appearance on a pigeon
      key. Grain always was delivered for 3 seconds at the end of the first stimulus
      interval. In the first experiment, autoshaped pecking of the stimulus preceding
      grain delivery began much sooner when that stimulus was a black vertical line on
      a white background and the other stimulus was green than when the opposite
      stimulus arrangement was used. Because these two stimuli differed in form, hue,
      brightness, and similarity in hue and brightness to the illumination of the
      raised feeder, three subsequent experiments examined whether the differential
      speed of autoshaping in the two groups was due to a feature-positive, feature
      negative effect, a preference for brighter over darker stimuli, a simple
      preference for white over green, or stimulus generalization from the brightness
      or hue of the illuminated, raised feeder to the stimulus on the key preceding
      grain delivery. The data from these experiments showed that the first autoshaped
      key peck was most likely to be made to the stimulus of the same hue as that
      illuminating the feeder, regardless of whether that stimulus was positively or
      negatively associated with grain delivery. At least under some conditions,
      therefore, stimulus-generalization mediated response transfer of pecking grain in
      the presence of the hue illuminating the feeder to pecking the key illuminated by
      a similar hue appears to account for the occurrence of autoshaped key pecking.

PMID- 16812008
TI  - Increased reinforcement when timeout from avoidance includes access to a safe
      place.
AB  - Three experiments investigated the reinforcing value of access to a safe place
      during timeout from an avoidance schedule. Rats were trained on conjoint
      schedules in which responding both postponed shock on a free-operant avoidance
      schedule and produced periods of timeout on fixed-ratio schedules. In some
      conditions, a shelf was inserted into the operant chamber during timeout,
      enabling subjects to get off the grid floor. The combination of timeout and shelf
      maintained substantially higher response rates than the baseline avoidance
      schedule with ratio requirements as high as 90 (Experiment I). Adding the shelf
      to timeouts in one component of multiple fixed-ratio schedules of timeout
      resulted in higher response rates in the component where the shelf was included
      (Experiment II). When timeouts with and without the shelf were arranged on
      concurrent schedules, the shelf-timeout combination was preferred, even when of
      shorter duration than timeout alone (Experiment III). In all three experiments,
      subjects climbed on the shelf, although all shocks were cancelled during timeout
      periods. The results could not be accounted for solely in terms of the
      reinforcing properties of changes in shock rates, but required an interpretation
      that ascribed conditioned reinforcing value to stimuli associated with such
      changes.

PMID- 16812009
TI  - Responding in the squirrel monkey under fixed-ratio schedules of stimulus
      termination.
AB  - Key pressing was maintained under a fixed-ratio schedule in which electric shock
      was scheduled for delivery at a fixed time (t seconds) after each stimulus onset,
      and every n(th) response terminated the stimulus and initiated a timeout from
      shock. Under this procedure, the higher the rate of responding, the briefer the
      duration of the stimulus presentation and the lower the frequency of shock
      delivery. The effects of several schedule parameters were studied to determine
      whether the maintenance of responding was dependent on an inverse relation
      between response rate and shock frequency. Shock rate and shock frequency were
      made independent of response rate by decreasing the value of t to 0.5 second and
      delivering shock only during the first presentation of the stimulus after a fixed
      time, including stimulus and timeout durations, had elapsed since the previous
      shock. The experiments showed that shock frequency and response rate are
      inversely related when t is of relatively long duration compared to the value of
      the fixed-ratio parameter, but that a decrease in shock rate or frequency due to
      a high rate of responding is not necessary for the maintenance of responding
      under a fixed-ratio schedule of stimulus termination.

PMID- 16812010
TI  - An operant analysis of human altruistic responding.
AB  - Human altruistic responding (called give responding), which delivered a
      reinforcer to someone other than the responder, was compared to responding where
      the responder was the recipient of the reinforcer (called earn responding). The
      same type of response (button pressing), the same reinforcer (a point
      representing a penny), and the same reinforcer contingency (a 40-response fixed
      ratio schedule) were used for both give and earn responding. Since points
      representing pennies were used to reinforce give and earn responding, responding
      for points not worth money was also assessed. Give, earn, and point responding
      were arranged as concurrent incompatible operants. Lowest rates were obtained for
      point responding. Compared to earn responding, give responding occurred at lower
      rates, was more susceptible to cessation when point responding was possible,
      extinguished more rapidly in the absence of money, and produced less responding
      during reconditioning compared to conditioning when reconditioning followed a
      period of nonreinforcement. Give responding was less when it reduced the giver's
      opportunity to earn. Finally, histories of getting reinforcement from others were
      shown to determine give responding.

PMID- 16812011
TI  - Operant conditioning in the guinea pig.

PMID- 16812012
TI  - Multiple and concurrent schedule performance: independence from concurrent and
      successive schedule contexts.
AB  - Six pigeons were trained on multiple variable-interval schedules and performance
      was measured in the presence or absence of another variable-interval schedule
      (the common schedule) arranged concurrently with both components. Manipulations
      included varying the rate of reinforcement on the common schedule, leaving the
      common schedule unchanged while the components of the multiple schedule were
      varied, varying the multiple schedule components in the absence of the common
      schedule, and varying one component of the multiple schedule while the other
      component and the common schedule were unchanged. The normal rate-increasing and
      rate-decreasing effects of reinforcement rate increase were found, except that
      changing one multiple schedule component did not affect the response rate in the
      successively available common schedule component. Both concurrent and multiple
      schedule performance undermatched obtained reinforcement-rate ratios, but the
      degree of undermatching in multiple schedules was reliably greater. Allocation of
      responses between multiple schedule components was unaffected by the concurrent
      availability of reinforcement, and allocation of responses between concurrent
      schedules was unaffected by the successive availability of different
      reinforcement rates.

PMID- 16812013
TI  - Choice, time allocation, and response rate during stimulus generalization.
AB  - Six pigeons were trained to discriminate between two noise intensities using a
      procedure that assessed choice, time allocation, and response rate simultaneously
      and independently. Responses on the left or right key (R1 or R2) were
      respectively correct in the presence of two different intensities, S1 and S2.
      After a correct response, reinforcement became available for pecks on the center
      key. Reinforcement density for R1|S1 relative to R2|S2 was varied across
      experimental conditions. Generalization tests followed extensive training at each
      condition. As a function of stimulus intensity, proportions of initial choices of
      R2, of time spent in R2-initiated components, and of center-key responses emitted
      in R2-initiated components all yielded sigmoidal gradients of similar slope,
      which shifted slightly in location when relative reinforcement density changed.
      Changeovers were maximal where initial choice proportions approximated 0.5.
      Gradients relating the absolute number of center-key responses to stimulus
      intensity were also roughly sigmoidal, but were more sensitive to changes in
      reinforcement density. Gradients of momentary response rate also depended on
      reinforcement density. During training, large but transitory shifts in choice
      responding occurred when reinforcement density changed, while differences in
      momentary response rate developed slowly, suggesting separate control of choice
      and response rate by the contingencies of reinforcement.

PMID- 16812014
TI  - Stimulus- and response-reinforcer contingencies in autoshaping, operant,
      classical, and omission training procedures in rats.
AB  - Separate groups of rats received 500 trials of lever-press training under
      autoshaping (food delivery followed 10-second lever presentations, or occurred
      immediately following a response); operant conditioning (responding was necessary
      for food delivery); and classical conditioning (food followed lever presentations
      regardless of responding). Each group then received 500 trials on an omission
      procedure in which food was omitted on trials with a response. Another group
      received 1000 trials on the omission procedure, and a fifth group, random
      control, received 1000 uncorrelated presentations of lever and food. The
      autoshaping, operant, and classical groups reached high response levels by the
      end of initial training. Acquisition was fastest in the autoshaping group.
      Responding remained consistently low in the control group. The omission group
      responded at a level between the control group and the other three groups. During
      omission training, responding in these three groups declined to the omission
      group level. During omission training, the rats continued contacting the lever
      frequently after lever pressing had declined. Response maintenance under omission
      training seems not to require topographic similarity between the response and
      reinforcer-elicited consummatory behaviors.

PMID- 16812015
TI  - A molecular analysis of multiple schedule interactions: negative contrast.
AB  - The present experiments investigated the relationship between changes in the
      relative reinforced interresponse-time distributions and the occurrence of
      positive and negative contrast in multiple variable-interval-variable-interval
      and multiple variable-interval-extinction schedules of reinforcement. Experiment
      I demonstrated that changes in the interresponse-time distributions were
      consistently correlated with response-rate changes referred to as positive and
      negative contrast. Corresponding changes in the reinforced interresponse-time
      distributions suggested that negative contrast resulted as an inductive effect of
      selectively reinforcing long interresponse times in the altered component at the
      moment the baseline schedule was reintroduced. Experiment II demonstrated that
      the magnitude of the negative-contrast effect could be significantly decreased if
      the altered component schedule was modified in order to prevent the reinforcement
      of these interresponse times during the first few sessions of baseline recovery.
      The results supported a proposal that interresponse time-reinforcer relations may
      act as amplifiers or attenuators of negative contrast.

PMID- 16812016
TI  - Escape, avoidance, punishment: where do we stand?
AB  - This paper reviews progress since the author's previous writings in three areas.
      In escape training, the preparatory-response explanation of bar holding still
      appears to be valid. In avoidance, the newer safety-signal version of two-factor
      theory has much to recommend it and readily incorporates Anger's conditioned
      aversive temporal stimuli formulation. Shock-density reduction is rejected as a
      substitute for two-factor theory. Finally, criticisms of the avoidance
      interpretation of punishment are answered and recent empirical data are cited in
      its support.

PMID- 16812017
TI  - A procedure for autoshaping the pigeon's key peck to an auditory stimulus.

PMID- 16812018
TI  - Effects of food deprivation and reinforcement magnitude on conditioned
      suppression.
AB  - In Experiment I, the responding of rats lever pressing on a variable-interval
      schedule for sucrose solution was partially suppressed by a variable duration
      conditioned stimulus followed by shock. When food deprivation was increased,
      response rates during and before the conditioned stimulus increased
      monotonically. Varying the concentration of sucrose across blocks of sessions or
      from session to session in a semi-random sequence had little effect on response
      rates either before or during the conditioned stimulus. With a fixed sequence of
      increasing concentrations across a five-session block, increased concentration
      produced much more rapid increases in response rates before than during the
      conditioned stimulus. In Experiment II, rats were presented with the same
      sequence of increasing concentrations across a five-session block. When tested at
      80% body weight, response rates increased rapidly as concentration increased, but
      at 100%, body-weight rates increased only slightly. The effect of a change in
      body weight in Experiment II thus mimicked the effect of the conditioned stimulus
      in the latter part of Experiment I. These findings support the view that the
      effect of a pre-aversive conditioned stimulus is similar to that of a change in
      food deprivation, but unlike that of a change in reinforcement magnitude.

PMID- 16812019
TI  - Parameters affecting the maintenance of negatively reinforced key pecking.
AB  - Three negative reinforcement experiments employing a key-peck response are
      described. In Experiment I, pigeons shocked on the average of twice per minute
      (imposed condition) could produce, by pecking a key, an alternate condition with
      correlated stimuli. Delayed shocks were added, across sessions, to the alternate
      condition until pecking stopped. Two of three pigeons continued to peck despite a
      100% increase in shock frequency. In Experiment II, pigeons were shocked in the
      imposed condition four times per minute. The postresponse delay to shock was held
      constant by delivering, in the alternate condition, the next shock, or the next
      two, three, or four shocks from the imposed-condition shock schedule. All three
      subjects continued to peck with no change in delay to the first two postresponse
      shocks but with a 75% reduction in shock frequency. In Experiment III, a response
      produced an immediate shock followed by a shock-free period. Three of four
      subjects continued to respond despite reduced delay to shock. Delay-to-shock or
      shock-frequency reduction was sufficient to maintain key pecking, but neither was
      necessary. The conditions that negatively reinforce the pigeon's key peck were
      similar to conditions that negatively reinforce the rat's bar press.

PMID- 16812020
TI  - Associative interaction: joint control of key pecking by stimulus-reinforcer and
      response-reinforcer relationships.
AB  - The joint control of rate of key pecking in pigeons by stimulus-reinforcer and
      response-reinforcer relationships was studied in the context of a two-component
      multiple schedule of reinforcement. Food presentation was always associated with
      one component and extinction with the other. The stimulus-reinforcer relationship
      was manipulated by varying the relative durations of the two components. In the
      food-presentation component, a fixed rate of reinforcement, independent of rate
      of responding, was generated by a schedule referred to as "T*". One aspect of the
      response-reinforcer relationship, contiguity, was manipulated by varying the
      percentage of delayed reinforcers. With the multiple T* extinction schedule,
      stimulus-reinforcer and response-reinforcer relationships could be varied
      independently of one another. Rate of key pecking was sensitive to manipulations
      of both relationships. However, significant differential effects due to either
      the stimulus-reinforcer or response-reinforcer relationship were obtained only
      when the other relationship was weak: stimulus-reinforcer and response-reinforcer
      relationships interacted in the joint control of responding.

PMID- 16812021
TI  - Duration and rate of reinforcement as determinants of concurrent responding.
AB  - The duration and frequency of food presentation were varied in concurrent
      variable-interval variable-interval schedules of reinforcement. In the first
      experiment, in which pigeons were exposed to a succession of eight different
      schedules, neither relative duration nor relative frequency of reinforcement had
      as great an effect on response distribution as they have when they are
      manipulated separately. These results supported those previously reported by
      Todorov (1973) and Schneider (1973). In a second experiment, each of seven
      pigeons was exposed to only one concurrent schedule in which the frequency and/or
      duration of reinforcement differed on the two keys. Under these conditions, each
      pigeon's relative rate of response closely matched the relative total access to
      food that each schedule provided. This result suggests that previous failures to
      obtain matching may be due to factors such as an insufficient length of exposure
      to each schedule or to the pigeons' repeated exposure to different concurrent
      schedules.

PMID- 16812022
TI  - Yoked variable-ratio and variable-interval responding in pigeons.
AB  - Pigeons' key pecks were maintained by variable-ratio or variable-interval
      schedules of food reinforcement. For pairs of pigeons in one group, variable
      ratio reinforcement was arranged for one pigeon's pecks; for the second pigeon,
      reinforcement was arranged according to a variable-interval schedule yoked to the
      interreinforcement times produced by the first pigeon. For pairs of pigeons in
      another group, variable-interval reinforcement was arranged for one pigeon's
      pecks; for the second pigeon, reinforcement was arranged according to a variable
      ratio schedule yoked to the interreinforcement responses produced by the first
      pigeon. For each pair, the yoking procedure was maintained for four or five
      consecutive sessions of 50 reinforcements each. In more than three-quarters of
      the pairs, variable-ratio response rates were higher than variable-interval rates
      within two sessions; in all cases, the rate difference developed within four
      sessions.

PMID- 16812023
TI  - On Herrnstein's equation and related forms.
AB  - In 1970, Herrnstein proposed a simple equation to describe the relation between
      response and reinforcement rates on interval schedules. Its empirical basis is
      firm, but its theoretical foundation is still uncertain. Two approaches to the
      derivation of Herrnstein's equation are discussed. It can be derived as the
      equilibrium solution to a process model equivalent to familiar linear-operator
      learning models. Modifications of this approach yield competing power-function
      formulations. The equation can also be derived from the assumption that response
      strength is proportional to reinforcement rate, given that there is a ceiling on
      response rate. The proportional relation can, in turn, be derived from a
      threshold assumption equivalent to Shimp's "momentary maximizing". This
      derivation implies that the two parameters of Herrnstein's equation should be
      correlated, and may explain its special utility in application to internal
      schedules.

PMID- 16812024
TI  - On the role of "memory" in the analysis of behavior.
AB  - Shimp's (1976) recent paper on memory and the structure of behavior is discussed,
      as is the concept of memory itself. Radical behaviorism is distinguished from
      associationism, and behavioral accounts of experiments on short-term and long
      term memory are provided. Unobservable theoretical quantities, such as rate of
      response, are distinguished from theoretical constructs such as memory. The
      logical inconsistency involved in the use of short-term memory as a "theoretical
      primitive" in the definition of units of behavior is explicated, and an
      alternative strategy for identifying units of behavior is presented. It is argued
      that the experimental analysis of behavior has ignored processes usually
      considered as memorial because many of the phenomena are irreversible. Methods
      for the study of transitions in single subjects should be developed more fully.
      Possible pitfalls associated with subscription to the term memory are listed, and
      it is concluded that the concept is neither required nor helpful in the analysis
      of behavior.

PMID- 16812025
TI  - Ivanov-Smolensky and operant conditioning: an historical note.

PMID- 16812026
TI  - Antecedents to Fechner's law: the astronomers J. Herschel, W. R. Dawes, and N. R.
      Pogson.
AB  - The history of the stellar magnitude scale is briefly traced from the second
      century b.c. until the middle of the nineteenth century. It becomes clear that
      astronomers formulated "Fechner's Law" by about 1850. While Fechner is credited
      with the grander view of things, the contention is made that the astronomers John
      Herschel, W. R. Dawes, and N. R. Pogson have not been given their due by
      historians of psychology.

PMID- 16812027
TI  - The role of preliminary magazine training in acquisition of the autoshaped key
      peck.
AB  - A series of experiments tested the hypothesis that initial key pecks in the
      autoshaping procedure are generalized pecks at the illuminated grain hopper.
      Experiment I found that autoshaping readily occurred when the chamber was
      continuously illuminated by a house-light. In Experiment II, pigeons given
      magazine training and autoshaping with an unlighted grain hopper failed to
      autoshape in 200 trials. Acquisition of autoshaped key pecking was retarded in
      Experiment III when stimulus control by the magazine light was reduced. In the
      fourth study, pigeons were given magazine training with either a red or white
      magazine light and then given autoshaping with concurrently presented red and
      white keys. For all pigeons in this experiment, the first key peck occurred on
      the key of the same color as that pigeon's magazine light. The results of these
      experiments were interpreted as supporting an account of autoshaping that
      identifies initial key pecks as arising due to generalization of pecking at the
      lighted grain hopper to pecking at the lighted key.

PMID- 16812028
TI  - Species differences in temporal control of behavior.
AB  - Temporal control of rats' and pigeons' responding was analyzed and compared in
      detail on fixed-interval and fixed-time schedules with parameters of 30, 60, and
      120 seconds. On fixed-time schedules, rats' responding decreased greatly or
      ceased, whereas pigeons continued to respond, especially on low schedule values.
      The running rate of responses (calculated by excluding the postreinforcement
      pause) was related to the duration of the preceding postreinforcement pause for
      rats but not for pigeons. Changes in response rate in successive segments of the
      interval were best described by normal curves. The relationship between midpoints
      of the normal curves and schedule value was a power function, with an exponent of
      less than one for pigeons but greater than one for rats. These differences could
      be explained in terms of a basic difference between the key-peck and lever-press
      responses, the two being differently affected by the response-eliciting
      properties of food.

PMID- 16812029
TI  - Fixed-ratio discrimination: effects of intermittent reinforcement.
AB  - Four pigeons had discrimination training that required the choice of a left side
      key after completing a fixed-ratio 10 on the center key, and a right side-key
      choice after fixed-ratio 20. Correct choices were reinforced on various fixed
      interval, fixed-ratio, random-interval, and random-ratio schedules. When
      performance was examined across successive 15-second intervals (fixed-interval
      and fixed-ratio schedules) accuracy was high in the first 15-second interval,
      decreased in one or several of the next 15-second intervals, and then increased
      again as reinforcement was approached. When performance was examined across
      correct trials on fixed-interval and fixed-ratio schedules, accuracy was lowest
      immediately after reinforcement, followed by a systematic increase in accuracy as
      the number of correct choices increased. These patterns were due primarily to
      errors on fixed-ratio 20 trials. Systematic accuracy patterns did not occur on
      random-interval or random-ratio schedules. The results indicate that when choice
      patterns differed on fixed-interval and fixed-ratio schedules, the differences
      were due to the method of data analysis.

PMID- 16812030
TI  - Conditioning of within-trial patterns of key pecking in pigeons.
AB  - The possibility of conditioning systematic patterns of responding during brief
      discrete trials was studied by requiring hungry pigeons to key peck and then
      pause or to pause and then key peck in order to gain access to food. These
      schedules were highly effective in promoting decelerated and accelerated rates of
      responding, respectively, within individual trials; indeed, performance was quite
      similar to that observed when explicit external stimuli were correlated with
      "peck" and "pause" portions of the daily trials. Finally, schedules of
      reinforcement that did not selectively reinforce peck-pause or pause-peck
      patterns neither generated these patterns nor maintained them at the previous
      high levels. The results, therefore, confirm Shimp's (1976) proposal that
      organized groupings of discrete responses may function as operants-even in the
      absence of strict response-reinforcer contiguity.

PMID- 16812031
TI  - Schedules of food postponement: II. Maintenance of behavior by food postponement
      and effects of the schedule parameter.
AB  - In Experiment I, food-deprived, feeder-trained squirrel monkeys pressed a lever
      to postpone brief electric shocks (Response-Shock=Shock-Shock interval=30
      seconds). Forty-one three-hour sessions of shock postponement were followed by
      120 sessions of concurrent shock and food postponement. The shock schedule was
      unchanged and the food schedule was Response-food interval-20 seconds, Food-food
      interval 10 seconds. After concurrent shock and food postponement, the shock
      schedule was discontinued and 40 sessions of food postponement ensued, followed
      by 53 sessions of extinction. After extinction, food postponement was resumed for
      11 sessions. Stable responding with low food rates was maintained under food
      postponement after the concurrent schedule. Responding decreased to low levels
      under extinction and recovered immediately to previous levels when the food
      postponement schedule was re-instated. In Experiment II, a parameter of the food
      postponement schedule was studied sequentially. Using the same subjects, the
      Response-food-Food-food interval was manipulated from four seconds to 80 seconds
      with several orders of presentation. Relations of response rates and food rates
      to the parameter were similar to those seen under shock postponement. Exposure to
      very short postponement times (four seconds), resulting in very high food rates,
      decreased but did not abolish subsequent responding at longer postponement times.
      Results are discussed from the point of view that reinforcing functions of
      stimuli consequent on responding depend on a prior history of scheduled contact
      with those stimuli.

PMID- 16812032
TI  - Fixed-interval matching-to-sample: intermatching time and intermatching error
      runs.
AB  - Four pigeons were trained on a matching-to-sample task in which reinforcers
      followed either the first matching response (fixed interval) or the fifth
      matching response (tandem fixed-interval fixed-ratio) that occurred 80 seconds or
      longer after the last reinforcement. Relative frequency distributions of the
      matching-to-sample responses that concluded intermatching times and runs of
      mismatches (intermatching error runs) were computed for the final matching
      responses directly followed by grain access and also for the three matching
      responses immediately preceding the final match. Comparison of these two
      distributions showed that the fixed-interval schedule arranged for the
      preferential reinforcement of matches concluding relatively extended
      intermatching times and runs of mismatches. Differences in matching accuracy and
      rate during the fixed interval, compared to the tandem fixed-interval fixed
      ratio, suggested that reinforcers following matches concluding various
      intermatching times and runs of mismatches influenced the rate and accuracy of
      the last few matches before grain access, but did not control rate and accuracy
      throughout the entire fixed-interval period.

PMID- 16812033
TI  - A study of misbehavior: token reinforcement in the rat.
AB  - The purpose of this research was to investigate the phenomenon of misbehavior
      described by Breland and Breland (1961). Rats were trained to obtain ball
      bearings and drop them in a hole for food or water reinforcers. In confirmation
      of the Brelands' observation, many subjects were slow to deliver the balls, and
      frequently attempted to chew them before they were dropped. A series of four
      experiments, in which the same rats were used throughout, showed that delivery
      times tended to be longer with food than with water, and that these times
      increased when nylon balls were substituted. The effect of motivational level was
      investigated by varying both deprivation and amount of prefeeding; no effect on
      delivery time was detected, although other measures of performance were affected
      by motivational factors. Similar results were obtained in a final experiment that
      employed a new set of naive subjects. The studies demonstrated that misbehavior
      can be studied in an experimental situation, and the results supported an
      analysis in terms of competition between stimulus-reinforcer and response
      reinforcer contingencies. The question of why such effects have not been reported
      in previous token reinforcer studies was unanswered.

PMID- 16812034
TI  - Conditioned reinforcement and choice.
AB  - In a series of three experiments, rats were exposed to successive schedule
      components arranged on two levers, in which lever pressing produced a light, and
      nose-key pressing produced water in 50% of the light periods. When one auditory
      signal was presented only during those light periods correlated with water on one
      lever, and a different signal was presented only during those light periods
      correlated with nonreinforcement on the other lever, the former lever was
      preferred in choice trials, and higher rates of responding were maintained on the
      former lever in nonchoice (forced) trials. Thus, the rats preferred a schedule
      component that included a conditioned reinforcer over one that did not, with the
      schedules of primary reinforcement and the information value of the signals
      equated. Preferences were maintained when one or the other of the auditory
      signals was deleted, but were not established in naive subjects when training
      began with either the positive or negative signal only. Discriminative control of
      nose-key pressing by the auditory signals was highly variable across subjects and
      was not correlated with choice.

PMID- 16812035
TI  - Stability criteria.
AB  - Three approaches to the determination of behavioral stability were examined. In
      the first, a learning curve was fit to acquisition data (from Cumming and
      Schoenfeld, 1960), and the "experiment" stopped when the data approached
      sufficiently close to the theoretical asymptote. In the second, the data were
      analyzed for variability and linear and quadratic trend. In the third, the
      experiment was stopped when the magnitude of the daily changes in the data fell
      below a criterion. Accuracy was measured as deviation between the average value
      of the dependent variable when the experiment was stopped, and the average value
      over the last 100 sessions. The first approach was most accurate, but at the cost
      of requiring the most sessions and being the most difficult to apply. Both the
      second and third approaches provided acceptable criteria with a reasonable cost
      accuracy tradeoff. The second approach permits a continuous adjustment of the
      criteria to accommodate the variability intrinsic in the experimental paradigm.
      The third, nomothetic, approach also takes into account the decreasing marginal
      utility of extended training sessions.

PMID- 16812036
TI  - Effect of varying the duration of grain presentation on automaintenance.
AB  - In a series of three experiments the effects of variation in grain duration on
      automaintenance were evaluated. In the first experiment, key illumination was
      followed by grain only when pigeons did not peck the key. Each subject was
      exposed to 2-, 4-, and 8-second feeder durations in blocks of 10 sessions.
      Subjects pecked on a high percentage of trials at all feeder durations. The mean
      peck latency was shorter in the 8-second condition than in the two other
      conditions in five of six subjects. The conditional probability of pecking given
      successive keylight-grain pairings did not increase as the number of pairings
      increased. The second experiment was identical to the first, except that key
      pecking had no scheduled consequence. Under these conditions, all three subjects
      showed substantial responding. The recorded measures showed no systematic
      relationship to feeder duration in this study. In the third experiment, two
      different stimuli were followed by feeder presentations of either identical (2-
      or 8-second) or different (2- and 8-second) durations within each session.
      Subjects tended to respond sooner and with a higher overall rate in the presence
      of the stimulus associated with the longer feeder duration only when different
      feeder durations were presented within the same session. This result was
      confirmed by direct observation of the pigeons. The results of these experiments
      suggest that the effects of varying grain duration may be small, compared to the
      effects of varying other variables. The results also suggest that the location as
      well as the frequency of pecking may be an important measure in the analysis of
      factors controlling the pigeon's key peck.

PMID- 16812037
TI  - Effects of component length and of the transitions among components in multiple
      schedules.
AB  - Pigeons received equal variable-interval reinforcement during presentations of
      two line-orientation stimuli while five other orientations appeared in
      extinction. Component duration was 30 seconds for all orientations and the
      sequence was arranged so that each orientation preceded itself and each other
      orientation equally often. The duration of one component (0 degrees ) was
      shortened to 10 seconds and the other (90 degrees ) was lengthened to 50 seconds.
      All animals showed large increases in response rate in the shortened component
      and this increase was recoverable after an interpolated condition in which all
      components were again 30 seconds in duration. This effect was replicated in a
      second experiment in which component duration was changed from 150 seconds to 50
      seconds and 250 seconds. An examination of local contrast effects during the
      first experiment showed that the shortened component produced local contrast
      during subsequent presentations of the lengthened component, just as would a
      component associated with more frequent reinforcement. When the presentation
      sequence was changed so that the lengthened component was always followed by the
      shortened component, response rates generally increased during the lengthened
      component. When the sequence was arranged so that the shortened component always
      preceded the longer component, response rate decreased in the former. These
      effects, as well as the increases in response rate following change in component
      length, seem not to be the product of local contrast effects among components.

PMID- 16812038
TI  - The symmetrical law of effect and the matching relation in choice behavior.
AB  - In a concurrent-chains procedure, pigeons chose between outcomes that differed in
      the rate of response-independent delivery of food and electric shocks. The
      application of functional measurement techniques confirmed the matching relation
      between choice and rate of reinforcement value-for two of three pigeons. Scale
      values of the outcomes were extracted for the two birds that conformed to
      matching, and the value of a single occurrence of shock per minute-in terms of
      negative food units-was estimated. A second experiment with concurrent chains
      provided a test of these parameter estimates. The close correspondence between
      predicted and obtained choice behavior found in Experiment II indicated that the
      estimates of outcome value were indeed reliable. Both experiments together
      support the contention that the effects on choice behavior of positive and
      aversive stimuli appear to be equal, though opposite in sign.

PMID- 16812039
TI  - Matching in concurrent variable-interval avoidance schedules.
AB  - After pretraining with multiple variable-interval avoidance schedules, two rats
      were exposed to a series of concurrent variable-interval avoidance schedules.
      Responses on two levers cancelled delivery of electric shocks arranged according
      to two independent variable-interval schedules. The ratio of responses and time
      spent on the two levers approximately matched the ratio of shocks avoided on
      each. Matching to the number of shocks received was not obtained. Concurrent
      variable-interval avoidance can therefore be added to the group of positive and
      negative reinforcement schedules that can be expressed in the quantitative
      framework of the matching law.

PMID- 16812040
TI  - Studies on responding under fixed-interval schedules of reinforcement: II. The
      scalloped pattern of the cumulative record.
AB  - Responding under fixed-interval schedules usually generates either scalloped or
      break-and-run cumulative records. Earlier, it was generally accepted that the
      characteristic pattern was the scallop, but in recent years there has been an
      increasing emphasis on the break-and-run pattern. The break-and-run pattern has
      been shown quantitatively to provide a good fit of certain fixed-interval
      patterns. In the present work, responding during fixed-interval 1000-second
      components of a multiple fixed-interval 1000-second fixed-ratio 50 responses
      schedule was examined in two rhesus monkeys. Even after responding had started in
      an interval, there was a high tendency for responding to accelerate over
      subsequent 100-second segments of the interval. In segments with responding, the
      rate increased from one segment to the next in 303 of 389 segments in one monkey
      and in 310 of 419 segments in the other. The size of the increase was
      substantial, the rate in the fifth segment after responding started being an
      average of 4.5 times higher than the rate in the first segment after responding
      started. Hence, the usual pattern of responding in individual intervals was of
      sustained and substantial acceleration, vindicating numerically the conclusion
      derived from inspection of the scalloped patterns of the cumulative records.

PMID- 16812041
TI  - Effects on choice of reinforcement delay and conditioned reinforcement.
AB  - Pigeons chose between fixed-interval schedules of different durations presented
      in the terminal links of concurrent-chains schedules. The pair of schedules was
      always in the ratio of 2:1, but the absolute duration of the fixed intervals
      varied. In one set of conditions, the different terminal-link schedules were
      associated with different keylight stimuli (cued conditions). In a second set of
      conditions, the different terminal-link schedules were associated with the same
      stimulus (uncued conditions). Results from the cued conditions replicated
      previous findings that preference for the shorter fixed-interval schedule
      increased with fixed-interval duration. Preferences in the uncued conditions were
      lower than in the corresponding cued conditions but also increased with fixed
      interval length. In addition, the degree of control under the uncued conditions
      was correlated with the extent to which the schedule during the terminal link was
      discriminated immediately upon entry into the terminal link. The pattern of
      results in both conditions was inconsistent with the notion that choice behavior
      matches relative immediacy of reinforcement. Reanalysis of previous evidence for
      matching (Chung and Herrnstein, 1967) showed that matching in fact did not occur,
      as the preferences of their subjects for the shorter of two delays also increased
      with the absolute size of the delays.

PMID- 16812042
TI  - Warmup in avoidance as a function of time since prior training.
AB  - On avoidance procedures, rats and pigeons typically show warmup effects,
      characterized by improving performance within sessions and loss of the
      improvement ("warmup decrement") between sessions. Between-session losses were
      examined by varying the time between periods of avoidance training. In one
      experiment, rats lived fulltime in conditioning chambers while intermission
      intervals were varied. In a second experiment, the animals lived in home cages
      between sessions; timeout intervals were introduced at midession, producing
      recurrence of warmup in the second half-session. In both experiments, the warmup
      decrements increased substantially as the timeout or intersession intervals were
      increased from zero to 30 minutes. With intervals of 60 or 120 minutes, the
      decrements approached or exceeded those obtained with intervals of a day or more.
      When avoidance was interposed between appetitive sessions, the appetitive
      responding was disrupted, but this seemed unrelated to the warmup or to the
      proficiency of avoidance. The warmup in avoidance shares characteristics with
      transient punishment effects, with the Kamin effect, and with habituation
      phenomena, but it is premature to assume that they reflect common processes.

PMID- 16812044
TI  - Effect of variable-interval punishment on the behavior of humans in variable
      interval schedules of monetary reinforcement.
AB  - One male and three female human subjects pressed a button for monetary
      reinforcement under a range of variable-interval schedules specifying different
      frequencies of reinforcement. On alternate days, responding was also punished (by
      subtraction of money) according to a variable-interval 170-second schedule. In
      the absence of punishment, the rate of responding was an increasing negatively
      accelerated function of reinforcement frequency, as predicted by Herrnstein's
      equation. The effect of the punishment schedule was to suppress responding under
      lower frequencies of reinforcement; responding under higher reinforcement
      frequencies was much less affected. This was reflected in an increase in the
      value of K(H) (the constant expressing the reinforcement frequency corresponding
      to the half-maximal response rate), whereas there was no significant change in
      the value of R(max) (the constant expressing the maximum response rate). Previous
      results had shown that variable-ratio punishment resulted in a change in the
      values of both constants (Bradshaw, Szabadi, and Bevan, 1977). The results of the
      present study were consistent with the concept that the suppressive effects of
      punishment on responding depend on the nature of the punishment schedule.

PMID- 16812043
TI  - Behavioral contrast as differential time allocation.
AB  - In Experiment I, hooded rats were exposed to multiple variable-interval schedules
      of reinforcement in which manipulanda and reinforcement magazines at opposite
      ends of the experimental chamber were associated with the different components.
      Time allocated to each component was measured by recording the time spent by the
      subject in the appropriate half of the chamber. Positive behavioral contrast was
      observed for the comparison between multiple variable-interval 30-second variable
      interval 30-second and multiple variable-interval 30-second variable-interval 90
      second conditions for both response frequency and time allocation measures, but
      not for mean local response rate (response frequency per time allocated to a
      component). In Experiment II, rats were exposed to multiple variable-time
      schedules in which reinforcement was response independent. Time allocated to each
      component was measured for two conditions, multiple variable-time 30-second
      variable-time 30-second and multiple variable-time 30-second variable-time 90
      second. Positive behavioral contrast of time allocation was exhibited. The
      results indicated that time allocation was differentially sensitive to changes in
      reinforcement probability, and that behavioral contrast may result from the
      differential allocation of time to the different components of the multiple
      schedule.

PMID- 16812045
TI  - Discriminative functions of schedule stimuli and memory: a combination of
      schedule and choice procedures.
AB  - Pigeons responded under a combination brief-stimulus schedule and choice
      procedure. Normally, a fixed-interval schedule was in effect, where completion
      randomly produced either a brief stimulus or food. Intermittently, this schedule
      was interrupted by a choice arrangement. Two choice keys were lit, either a short
      or a long time since a prior event (food or stimulus). One choice response
      produced food if the time had been short, and the alternate response produced
      food if the time had been long. Across conditions, the duration of the fixed
      interval schedule was varied, the stimuli that comprised the brief-stimulus
      operation were changed, and the stimuli were presented as paired and nonpaired
      with food. The focus of the study was the control of both schedule performance
      and choice responding across conditions. The results showed that choice accuracy
      was correlated with the degree of fixed-interval curvature, the response pattern
      of a pause followed by a gradually accelerated rate. As fixed-interval schedule
      duration was increased, both the degree of fixed-interval curvature and choice
      accuracy decreased. The particular brief stimulus used affected schedule and
      choice performance, with a more salient stimulus producing a greater degree of
      curvature and higher accuracy. Pairing and nonpairing operations produced
      striking differences in performance with the less salient brief stimulus, but not
      with the more salient stimulus. The results suggest that brief-stimulus schedule
      performance may be conceptualized in the context of memory research.

PMID- 16812046
TI  - Choice performance in several concurrent key-peck treadle-press reinforcement
      schedules.
AB  - Five pigeons were exposed to several concurrent variable-interval food
      reinforcement schedules. For three subjects, one component of the schedule
      required a key-pecking response, the other a treadle-pressing response. For the
      other two subjects, both schedule components required treadle-pressing responses.
      The relative probability of reinforcement associated with the manipulanda was
      varied from 0 to 1.0 in 13 experimental conditions for the Key-Treadle subjects
      and nine conditions for the Treadle-Treadle subjects. The results indicated that
      the logarithms of relative time spent responding, and the logarithms of relative
      number of responses emitted on a manipulandum, approximated direct linear
      functions of logarithms of the relative frequencies of reinforcement associated
      with that manipulandum. No systematic bias in favor of time spent key pecking
      over time spent treadle pressing was apparent for the Key-Treadle subjects. All
      subjects exhibited undermatching, in that the ratios of time and response
      allocation at the alternatives systematically differed from the ratios of
      reinforcers obtained from the alternatives in the direction of indifference. Key
      pecking appeared to have no special link to food beyond treadle pressing or what
      would be expected on the basis of the reinforcement dependencies alone.

PMID- 16812047
TI  - Time-allocation matching between punishing situations.
AB  - In the presence and absence of white noise, response-independent aversive events
      were delivered to rats according to several variable-time electric-shock
      schedules. The animals could switch from the noise component to the no-noise
      component and vice versa by making a single lever-press response. If the schedule
      in one component was not in operation when the animal was in the other component,
      the proportion of time allocated to one component equalled or matched the
      proportion of obtained punishers in the other component. If both schedules were
      always in operation, minimizing tended to occur: the animals allocated almost all
      of their time to the component having the lower shock rate. An analysis of these
      results, in terms of the expected time until an aversive event, is presented.

PMID- 16812048
TI  - Time-dependent changes in conditioned suppression.
AB  - Time-dependent changes in a response following aversive conditioning were
      investigated using a conditioned suppression procedure in a within-subjects
      design. Four groups of pigeons received Pavlovian conditioning "off the
      baseline", immediately followed by an operant task. During the Pavlovian phase,
      two groups received a forward pairing of a tone with shock, one group received a
      backward pairing, and one group received a truly random pairing. One of the
      forward pairing groups also received a delay between the Pavlovian and operant
      phases. For all groups, key pecking was reinforced on a variable-interval
      schedule during the operant phase. Testing sessions were identical to training
      sessions, except that the tone used during Pavlovian conditioning was presented
      either 0, 15, 30, 45, of 60 minutes after the operant phase began. Testing
      sessions in which the Pavlovian phase was omitted were also included. The results
      showed suppression to change as a function of the retention interval, with
      maximum suppression occurring at intermediate intervals. This U-shaped function
      was obtained for 11 of the 12 pigeons in the forward-pairing groups and for three
      of the five in the truly random group. Pigeons in the background pairing group
      did not show changes in suppression as a function of the retention interval.

PMID- 16812049
TI  - Conservation, choice, and the concurrent fixed-ratio schedule.
AB  - Five rats got all of their water in daily 60-minute sessions. Two levers and a
      water spout were freely available throughout baseline sessions. Contingency
      sessions offered a choice between two alternative fixed-ratio components, in the
      form of a choice between the two levers. Each component required a specified
      number of lever presses for access to the spout, and then a specified number of
      licks for another choice between components. Given the observed relative
      frequency, the absolute frequency of selecting each component was predicted
      accurately by assuming that the subject conserved between baseline and
      contingency the total amount of a dimension attributable to lever pressing and
      licking. Several quantitative models for predicting relative frequency were
      examined. The best of these assumed that the subject would show a nonexclusive
      preference for the component requiring fewer lever presses.

PMID- 16812050
TI  - Repeated acquisition of conditional discriminations.
AB  - A new technique was developed to study the repeated acquisition of conditional
      discriminations. Using a discrete trial procedure, pigeons were required to learn
      during each session a different two-member chain of conditional discriminations.
      Key color and geometric forms were used as stimuli. After the pigeons had reached
      a steady state of relearning (40 to 60 sessions), the technique was used to
      investigate variables that have previously been shown to affect the repeated
      acquisition of response sequences. Various (0 to 90 seconds) durations of timeout
      for errors were investigated in Experiment I. The stimulus change associated with
      a timeout, rather than its duration, was found to be the critical variable in
      acquisition of the discrimination. Extended training on a single chain was found
      to reduce total errors across sessions in Experiment II. Extended training (three
      sessions) did not, however, change the pattern of within-session error reduction.
      In some cases, extended training facilitated acquisition of a partially reversed
      discrimination. In Experiment III, color rather than chain position was found to
      control behavior, for three of the four birds, as the second stimulus dimension
      in the conditional situation. The results of these experiments replicate and
      extend previous findings concerning some of the variables that affect the
      repeated acquisition of response sequences.

PMID- 16812051
TI  - Contrast effects in multiple fixed-interval reinforcement schedules.
AB  - Pigeons were exposed to a multiple fixed-interval one-minute fixed-interval three
      minute schedule of reinforcement following training on either a multiple fixed
      interval one-minute fixed-interval one-minute schedule or a multiple fixed
      interval three-minute fixed-interval three-minute schedule. For all birds, large
      negative local contrast effects developed during the first of four three-minute
      intervals in a component; response rate was depressed and postreinforcement pause
      lengthened in this interval. Positive local contrast effects were evident during
      the first of 12 one-minute intervals in a component for five of six birds; at
      asymptote, the pause was very short and response rate slightly elevated during
      this interval. Overall positive contrast was generally transient and varied
      considerably across subjects, while overall negative contrast effects, if they
      occurred, appeared only after a large number of sessions.

PMID- 16812053
TI  - A comparison of forward and backward procedures for the acquisition of response
      chains in humans.
AB  - Ten university students each learned four separate six-link response chains, two
      forward and two backward. All 10 subjects made fewer errors in the forward
      procedure. It was concluded that the forward procedure is superior because each
      link of the response chain is acquired by direct reinforcement.

PMID- 16812052
TI  - Acceleration and suppression of rats' responding to avoid foot shock and tail
      shock.
AB  - Signalled response-independent shocks were superimposed on rats' wheel-turn
      responding to avoid shock administered to their feet through a grid floor or to
      their tails through fixed electrodes. In Experiment I, a tone paired with
      response-independent foot shock increased responding in three of four rats; a
      tone paired with tail shock increased responding in only one of four rats and
      suppressed responding in two rats. In Experiment II, a tone presented randomly
      with respect to response-independent shock had no reliable effect on responding
      to avoid foot shock or tail shock. In Experiment III, tail shock and foot shock
      were compared in a within-subject design while the temporal pattern of responding
      during conditioned stimuli was recorded. Responding during the conditioned
      stimulus preceding foot shock was characterized by initial suppression of
      responding at tone onset, followed by increased responding just before response
      independent shock. Responding was suppressed throughout the conditioned stimulus
      preceding tail shock. Foot shock elicited bursts of responding, but tail shock
      did not.

PMID- 16812054
TI  - Responding under schedules combining response-dependent and response-independent
      shock delivery.
AB  - Lever pressing of three squirrel monkeys with experience under continuous
      avoidance schedules was maintained by response-produced shock under a 5-minute
      variable-interval schedule. Responding decreased when half of the scheduled
      shocks were delivered independently of lever pressing and decreased further when
      all shocks were independent of lever pressing. Responding was lowest when all
      shocks were eliminated. When the proportion of response-dependent shocks
      increased, responding increased. This relation occurred even though the frequency
      and temporal distribution of shock delivery remained the same. Responding of two
      monkeys increased in a graded fashion as the frequency of shock was increased by
      arranging variable-time 5-minute, 2-minute, and 1-minute schedules jointly with
      the variable-interval 5-minute schedule. Thus, increasing the proportion of
      response-independent shocks decreased responding when the overall frequency of
      shocks stayed the same, but increased responding when the overall frequency of
      shock delivery increased.

PMID- 16812055
TI  - Lever attacking and pressing as a function of conditioning and extinguishing a
      lever-press avoidance response in rats.
AB  - Six experimental rats were conditioned to press one of two available levers to
      avoid shock. The levers registered bites as well as presses. For four of these
      rats, shock was contingent on lever bites when a specified time period had
      elapsed after the previous shock. An extinction period, in which only periodic
      noncontingent shocks were presented, followed avoidance training. Six yoked
      control rats received the same sequence of shocks as did the corresponding
      experimental rats in both the conditioning and extinction phases. All six
      experimental rats repeatedly bit the avoidance lever. Four bit it more than the
      nonavoidance lever during conditioning, and five bit it more during extinction.
      Five of the six experimental rats consistently bit the levers many more times
      during each session than did their respective control rats, suggesting that
      avoidance conditioning facilitated lever biting. Rates of lever biting and
      pressing by all of the experimental rats and by some of the control rats were
      highest immediately following shock throughout both phases. During later portions
      of the intervals following shock, characteristic effects of conditioning and
      extinction were observed. This finding suggests that extinction of avoidance
      behavior by unavoidable shock presentations can be demonstrated more readily when
      shock-elicited responding is extricated from the data.

PMID- 16812056
TI  - The effects of different component response requirements in multiple and
      concurrent schedules.
AB  - Six pigeons were trained on multiple and concurrent schedules. The reinforcement
      rates were varied systematically (a) when lever pressing was required in one
      component and key pecking in the successive component; (b) when lever pressing
      was required in both multiple components; (c) when key pecking was required in
      both multiple components; and (d) when key pecking was required on one schedule
      and lever pressing was required on the concurrently-available schedule. Only the
      absolute level of responding was changed by different response requirements.
      Analyzed by the generalized matching law, performance under different response
      requirements resulted in a bias toward key pecking, and the measured response
      bias was the same in multiple and concurrent schedule arrangements. The bias in
      time measures obtained from concurrent schedule performance was reliably smaller
      than the obtained response biases. The sensitivity to reinforcement-rate changes
      was ordered: concurrent key-lever; multiple key-key; multiple lever-key; and, the
      least sensitive, multiple lever-lever. The results confirm that requirements of
      different topographical responses can be handled by the generalized matching law
      mainly in the bias parameter, but problems for this type of analysis may be
      caused by the changing sensitivity to reinforcement in multiple schedule
      performance as response requirements are changed.

PMID- 16812057
TI  - Stimulus-reinforcer contingencies and local behavioral contrast.
AB  - Four pigeons were exposed to a series of multiple schedules of variable-interval
      reinforcement in which pecks were required on one key (operant key) and
      components were signalled on a second key (signal key). Four additional pigeons
      experienced identical conditions, except that a yoking procedure delivered food
      on variable-time schedules, with no key pecks required. One of the components of
      the multiple schedule was constant throughout the experiment as a variable
      interval (or variable-time) 30-second schedule. Operant-key responding during the
      constant component was uniform throughout the component, uninfluenced by changes
      in the duration of the variable component, and only slightly influenced by
      changes in reinforcement frequency correlated with the variable component. By
      comparison, signal-key response rate during the constant component was highest at
      the onset of the component, was higher when the variable component was 60-sec
      long than when it was 1-sec long, and was higher when no reinforcement occurred
      in the variable component than when reinforcement was scheduled in the variable
      component. These characteristics of signal-key pecking matched characteristics of
      local positive behavioral contrast. These data are taken to support the
      "additivity theory" of behavioral contrast and to suggest that Pavlovian stimulus
      reinforcer relations contribute primarily to the phenomenon of local positive
      contrast.

PMID- 16812058
TI  - Effects of a pairing contingency on behavior in a three-person programmed
      environment.
AB  - Four groups of three subjects resided for 10 days within a continuously
      programmed environment. Subjects followed a behavioral program of contingently
      scheduled activities that determined individual and social behaviors. A triadic
      condition was in effect when all three subjects were required to select
      simultaneous access to a group area before it became available for a social
      episode. A dyadic condition was in effect when access to a group area was
      permitted to any combination of two, and only two, subjects. The effects of these
      two conditions on individual and social behaviors were studied in reversal
      designs with several successive days devoted to each condition. Results showed
      that durations of social activities and synchronization of individual activities
      were greater during triadic conditions than during dyadic conditions. Under both
      conditions, wake-sleep cycles departed from a typical day-night rhythm for most
      subjects. Instances when subjects did not respond to each others' attempts to
      initiate conversations using the intercom were generally more frequent during
      dyadic than triadic conditions. Physical distance during triadic social episodes
      was found to be related to sociability levels during dyadic conditions.

PMID- 16812059
TI  - The relation between the generalized matching law and signal-detection theory.
AB  - The generalized matching law can be applied to a signal-detection matrix to give
      two equations. The first relates responding in the presence of the stimulus to
      the reinforcements for the responses, and the second relates responding in the
      absence of the stimulus to the reinforcements for the responses. Evidence for
      stimulus discrimination is given by biases that are opposite in sign in the two
      equations. As the logarithmic ratio and z proportion transformations are similar,
      the combination of the absolute values of the two logarithmic biases gives a
      measure equivalent to the signal-detection measures d' and eta. The two equations
      can also be combined to eliminate the biases caused by the signalling stimuli and
      to produce a generalized matching-law statement relating overall performance to
      the obtained reinforcements.

PMID- 16812060
TI  - An alternative target in the study of schedule-induced aggression in pigeons.

PMID- 16812061
TI  - Pressurized air as a punisher.

PMID- 16812062
TI  - Species differences in temporal control of behavior II: human performance.
AB  - Human subjects responded on two panels. A differential-reinforcement-of-low-rate
      schedule with a limited-hold contingency operated on Panel A. In Condition 1,
      responses on Panel B produced a stimulus on the panel that signalled whether
      reinforcement was available on Panel A. In Condition 2, responses on Panel B
      briefly illuminated a digital clock. In both conditions, performance on Panel A
      was very efficient; with few exceptions, Panel A was pressed only when
      reinforcement was available. Thus, in effect, a fixed-interval schedule operated
      on Panel B. In Condition 1, a "break-and-run" response pattern occurred on Panel
      B; with increasing temporal parameters, the duration of the postreinforcement
      pause on Panel B increased linearly while overall response rate and running rate
      (calculated by excluding the postreinforcement pauses) remained approximately
      constant. In Condition 2, the response pattern on Panel B was scalloped; the
      postreinforcement pause was a negatively accelerated increasing function of
      schedule value, while overall response rate and running rate were negatively
      accelerated decreasing functions of schedule value. The performance of subjects
      in Condition 2, but not in Condition 1, was highly sensitive to the contingencies
      in operation, and resembled that of other species on the fixed-interval schedule.

PMID- 16812063
TI  - Clustering in the output of behavior.
AB  - Pigeons exposed to fixed-interval schedules of 3, 5, 15, 40, and 120 minutes all
      maintained considerable variability in daily response rates for as many as 104
      sessions. However, variations did not occur at random. Instead, rate in a session
      appeared dependent on those occurring previously. The series displayed a wave
      like form arising because a group of high rates was followed by a group of low
      rates and vice versa. These sequential relations produced a curve having
      irregular periodicity, sometimes superimposed on a declining or rising linear
      trend. Whether grouping of response rates stemmed from experimental or extra
      experimental sources was not determined. If the phenomenon was either totally or
      partially produced by the schedule itself, it suggests that response rate is
      determined by a combination of positive and negative feedback. Control by factors
      extrinisic to the experiment itself implies that response rate may be influenced
      by some rhythmic physiological process.

PMID- 16812064
TI  - Behavior simultaneously maintained by both presentation and termination of
      noxious stimuli.
AB  - Lever pressing by two squirrel monkeys was maintained under a 3-minute variable
      interval schedule of response-produced electric-shock presentation. At the same
      time, responding on a second lever was maintained under a 3-minute fixed-interval
      schedule of termination of the shock-presentation schedule and shock-correlated
      stimuli. Under the termination schedule, the first response after a 3-minute
      period produced a 1-minute timeout, during which no events occurred and
      responding had no scheduled consequence. Relatively high and constant rates of
      responding were maintained on the lever where responding produced shock. Lower
      rates and positively accelerated patterns of responding occurred on the lever
      where responding terminated the shock schedule. Thus, responding was
      simultaneously maintained by presentation of an event and by termination of a
      stimulus associated with that event. Rates and patterns of responding on each
      lever were reversed when the schedules arranged on each lever were reversed on
      two occasions. When shock intensity was increased from 0 to 10 mA, responding
      maintained both by presentation of shock and by termination of the shock schedule
      increased, but responding maintained by shock presentation increased to a greater
      extent. Positive and negative reinforcement, usually regarded as separate
      behavioral processes involving different events, can coexist when behavior is
      controlled by different contingencies involving the same event.

PMID- 16812065
TI  - Conditioned reinforcement and discrimination in second-order schedules.
AB  - Pigeons were exposed to multiple second-order schedules in which responding on
      the "main key" was reinforced according to either a variable-interval or fixed
      interval schedule by production of a brief stimulus on the "brief-stimulus key".
      A response was required to the brief stimulus during its fourth (final)
      presentation to produce food; responses to the earlier brief stimuli indicated
      the extent to which the final brief stimulus was discriminated from preceding
      ones. Main-key response rates were higher in early components of paired brief
      stimulus schedules, in which each brief stimulus was the same as that paired with
      reinforcement, than in comparable unpaired brief-stimulus or tandem schedules.
      Poor discrimination occurred between paired brief stimuli (Experiment I). When
      chain stimuli on the main key induced a discrimination between the first two and
      second two brief stimuli, the response-rate enhancement in the paired brief
      stimulus schedule persisted (Experiment II). Rate enhancement diminished when the
      initial link of the chain included the first three components (Experiment IV).
      Eliminating the contingency between responding and brief-stimulus production also
      diminished rate enhancement (Experiment III). The results show that the
      discriminative and conditioned reinforcing effects of food-paired brief stimuli
      may be selectively manipulated and suggest that the reinforcing effects are
      modulated by other reinforcers in the situation.

PMID- 16812066
TI  - Time allocation in concurrent schedules: the effect of signalled reinforcement.
AB  - The responses of five pigeons were reinforced on concurrent variable-interval
      variable-interval reinforcement schedules in which changeover key responses
      changed the stimulus and reinforcement schedules associated with the food key.
      While the reinforcement availability in one component remained unchanged
      throughout the experiment, the reinforcement availability in the other component
      was, during several conditions, signalled by the onset of an additional
      discriminative stimulus. During unsignalled conditions, both the relative
      frequency of responding and the relative time spent in each component
      approximated the obtained relative reinforcement frequency in each component. The
      effect of signalling reinforcer availability in one component was to (1) reduce
      responding in the signalled component to near-zero levels, and (2) increase the
      relative time in the unsignalled component, without a corresponding increase in
      the obtained relative reinforcement frequency. The magnitude of the increase in
      relative time in the unsignalled component decreased as the overall frequency of
      reinforcement increased. This deviation in the matching relation between relative
      time and the obtained relative reinforcement frequency was eliminated if the
      overall reinforcement frequency was increased before the signal was introduced
      and then, without removing the signal, gradually reduced.

PMID- 16812067
TI  - Local response-rate constancy on concurrent variable-interval schedules of
      reinforcement.
AB  - Concurrent variable-interval schedules were arranged with a main key that
      alternated in color and schedule assignment, along with a changeover key on which
      a small fixed ratio was required to changeover. Acceptable matching was observed
      with pigeons in two replications, but there was a tendency toward overmatching.
      Local response rates were found to differ for unequal schedules of a concurrent
      pair: local response rate was greater for the variable-interval schedule with the
      smaller average interreinforcement interval, but qualifications based on an
      interresponse-time analysis were discussed. In a second experiment, two 3-minute
      variable-interval schedules were arranged concurrently, and the experimental
      variable was the changeover procedure: either a changeover delay was incurred by
      each changeover or a small fixed ratio on a changeover key was required to
      complete a changeover. Changeover delays of 2 and 5 seconds were compared with a
      fixed-ratio changeover of five responses. The response output on the main key
      (associated with the variable-interval schedules) was greater when a changeover
      delay was arranged than when a fixed ratio was required to changeover. A detailed
      analysis of stripchart records showed that a 2-second delay generated an
      increased response rate for 3 seconds after a changeover, while the fixed-ratio
      requirement generated an increased rate during the first second only, followed by
      a depressed response rate for 2 seconds.

PMID- 16812068
TI  - Relationship between response rate and reinforcement frequency in variable
      interval schedules: the effect of the concentration of sucrose reinforcement.
AB  - Four rats were exposed to variable-interval schedules specifying a range of
      different reinforcement frequencies, using sucrose of two different
      concentrations and distilled water as the reinforcer. With sucrose, the rates of
      responding of all four rats were increasing negatively accelerated functions of
      reinforcement frequency, the data conforming closely to Herrnstein's equation;
      this was also true of the data from three of the four rats when distilled water
      was used as the reinforcer. The values of both constants in Herrnstein's equation
      were related to the sucrose concentration: the asymptotic response rate
      decreased, and the reinforcement frequency corresponding to the half-maximal
      response rate increased, with decreasing sucrose concentration.

PMID- 16812069
TI  - Matching, contrast, and equalizing in the concurrent lever-press responding of
      rats.
AB  - Five rats pressed levers for food reinforces delivered by several concurrent
      variable-interval variable-interval schedules. The rate of reinforcement
      available for responding on one component schedule was held constant at 60
      reinforcers per hour. The rate of reinforcement available for responding on the
      other schedule varied from 30 to 240 reinforcers per hour. The behavior of the
      rats resembled the behavior of pigeons pecking keys for food reinforcers. The
      ratio of the overall rates of responding emitted under, and the ratio of the time
      spent responding under, the two components of each concurrent schedule were
      approximately equal to the ratio of the overall rates of reinforcement obtained
      from the components. The overall rate of responding emitted under, and the time
      spent responding under, the variable component schedule varied directly with the
      overall rate of reinforcement from that schedule. The overall rate of responding
      emitted under, and the time spent responding under, the constant component
      schedule varied inversely with the overall rate of reinforcement obtained from
      the variable component. The local rates of responding emitted under, and the
      local rates of reinforcement obtained from, the two components did not differ
      consistently across subjects. But they were not exactly equal either.

PMID- 16812070
TI  - Negative behavioral contrast on multiple treadle-press schedules.
AB  - Eight pigeons pressed treadles for food reinforcers delivered by several multiple
      variable-interval schedules. The rate of reinforcement for responding during one
      component schedule was held constant at 30 reinforcers per hour. The rate of
      reinforcement for responding during the other component varied from 0 to 120 or
      240 reinforcers per hour. The schedules were presented in different orders for
      different subjects. The rate of responding emitted during the variable component
      schedule varied directly with the rate of reinforcement it provided. The rate of
      responding during the constant component did not increase consistently when the
      rate of reinforcement obtained from the variable component decreased from 30 to 0
      reinforcers per hr. The rate of responding emitted during the constant component
      decreased when the rate of reinforcement obtained from the variable component
      increased from 30 reinforcers per hour to a higher rate. That is, negative but
      not positive behavioral contrast occurred. The failure to find positive contrast
      is consistent with one of the predictions of the additive theories of behavioral
      contrast. Finding negative contrast has ambiguous implications for the additive
      theories.

PMID- 16812071
TI  - The economics of daily consumption controlling food- and water-reinforced
      responding.
AB  - In the first experiment, two rhesus monkeys earned their entire ration of food
      and water during daily sessions with no provisions to ensure constant daily
      intakes. Two variable-interval schedules of food presentations were concurrent
      with one variable-interval schedule of water presentations; the maximum rate of
      food presentations arranged by one food schedule was varied. As the rate of food
      presentations was increased, the absolute level of responding on the two food
      schedules combined decreased, while responding on the water schedule increased.
      The preference for the variable food schedule compared to the other food schedule
      approximately matched the proportion of reinforcers obtained from it. The
      preference for the variable food schedule compared to the water schedule did not
      match, but greatly decreased, as the proportion of reinforcers from the food
      schedule increased. When Experiment I was replicated, with provisions to ensure
      constant daily intakes of food and water (Experiment II), the absolute response
      rates under the two food schedules combined and under the water schedule no
      longer changed with increases in the rate of food during the sessions. On the
      other hand, choice between the two food schedules remained proportional to the
      distribution of obtained food pellets. These results were interpreted as
      indicating that behavior to obtain nonsubstitutable commodities, such as food and
      water, is strongly controlled by the economic conditions of daily consumption,
      while choice between substitutable commodities is independent of these factors.

PMID- 16812072
TI  - Schedule-induced polydipsia in rats living in an operant environment.
AB  - The effect of variations in interreinforcement interval on the temporal and
      distributional relation between feeding and drinking was continuously monitored.
      Rats were housed continuously in an operant chamber in which water was freely
      available, but lever pressing was required to obtain food (45-mg pellets).
      Initially, pellets were delivered on a fixed-ratio 1 schedule of reinforcement,
      which was followed by testing on response-initiated fixed-interval 15-, 30-, and
      60-second schedules. The total number of discrete, daily meals (a period in which
      several pellets were earned in succession) was slightly higher during the fixed
      interval schedules than during the fixed-ratio 1, but there was no systematic
      effect of fixed-interval length on meal frequency. Total water consumption, in
      contrast, increased dramatically as the interval was lengthened: both subjects
      consumed two to three times as much water on the fixed-interval 60-second
      schedule as on the fixed-ratio 1. The increased water consumption was the result
      of an alteration in the distribution of drinking relative to eating. During the
      fixed-ratio 1 condition, drinking occurred infrequently following individual food
      pellets and represented the smallest percentage of total drinking; drinking
      occurred predominantly just before or after a meal. As the fixed interval was
      lengthened, however, the frequency of postpellet drinking gradually increased and
      eventually comprised the largest proportion of daily drinking.

PMID- 16812073
TI  - Additive summation following intradimensional discrimination training.
AB  - Rats were exposed to intradimensional composite stimuli presented on the response
      lever that varied in both light intensity and flicker rate. For all subjects,
      pressing the lever was reinforced when it was illuminated at a high intensity and
      flickered at a low rate (I + f) or when it was illuminated at a low intensity and
      flickered at a high rate (i + F). For half the subjects, lever responding was not
      reinforced when it was illuminated at a low intensity and flickering at a low
      rate (i + f). For the remaining subjects, lever presses were not reinforced when
      the lever was illuminated at a high intensity and flickered at a high rate (I +
      F). When the composite stimulus composed of the light intensity and flicker rates
      that had been associated only with reinforced responding was displayed (I + F for
      half the subjects and i + f for the remaining subjects), it controlled the
      highest response rate of all stimuli (additive summation). The results
      demonstrated that similar attentional processes control intra- and
      interdimensional composite-stimulus discriminations in a manner consistent with
      Weiss' (1972) analysis of summation.

PMID- 16812074
TI  - The role of physical identity of the sample and correct comparison stimulus in
      matching-to-sample paradigms.
AB  - Pigeons were trained in a higher-order conditional discrimination paradigm to
      assess the role of physical identity in a within-subjects design. A line
      orientation which was super-imposed on all response keys signalled whether a
      response to the matching color or a response to the nonmatching color was
      correct. Following training under this paradigm, stimulus control gradients were
      obtained by varying the angularity of the lines. Orderly gradients of stimulus
      control were obtained and no bias toward or away from the physically identical
      comparison stimulus was observed. The data were interpreted as indicating that
      the pigeons acquired a discrimination for each specific stimulus configuration or
      a set of specific stimulus-response chains based on compound stimuli in which
      physical identity played no special role.

PMID- 16812075
TI  - Effects of error and errorless discrimination acquisition on reversal learning.
AB  - The effectiveness of trial-and-error, graded-choice, and verbal-instruction
      procedures on the acquisition and maintenance of a two-choice simultaneous color
      discrimination in an intradimensional double-reversal learning situation was
      studied using 18 first-grade children. After acquiring a red-green discrimination
      during one 70-trial session, the discriminative roles of the stimuli were
      reversed for 30 trials, followed by a second reversal for 30 trials. Children in
      the graded-choice and verbal-instruction groups acquired and maintained the
      discriminations with fewer errors than children who learned by trial and error.
      The importance of the results in terms of two-stage discrimination learning
      theories is pointed out and similarities between errorless learning and
      overtraining are discussed.

PMID- 16812077
TI  - Beyond the relational principle of reinforcement.
AB  - Behavior under baseline conditions in which the contingency is absent can shed
      some light on the individual's performance under a schedule, but is insufficient
      as a basis for prediction of performance. This insufficiency of the baseline data
      runs counter to a recent formalization of the relational principle of
      reinforcement (Donahoe, 1977). A more satisfactory predictive model must
      incorporate not only the baseline level of the instrumental response and that of
      the contingent response, but also the schedule requirements, the character of
      each response in relation to the other, and the behavior required in simply
      switching from each to the other.

PMID- 16812076
TI  - Response rate and changeover performance on concurrent variable-interval
      schedules.
AB  - Six pigeons were exposed to variable-interval schedules arranged on one, two,
      three, and four response keys. The reinforcement rate was also varied across
      conditions. Numbers of responses, the time spent responding, the number of
      reinforcements, and the number of changeovers between keys were recorded.
      Response rates on each key were an increasing function of reinforcement rate on
      that key and a decreasing function of the reinforcement rate on other keys.
      Response and time-allocation ratios under-matched ratios of obtained
      reinforcements. Three sets of equations were developed to express changeover rate
      as a function of response rate, time allocation, and reinforcement rate
      respectively. These functions were then applied to a broad range of experiments
      in the literature in order to test their generality. Further expressions were
      developed to account for changeover rates reported in experiments where
      changeover delays were varied.

PMID- 16812078
TI  - Distribution of response ratios in concurrent variable-interval performance.

PMID- 16812079
TI  - Complex learning and information processing by pigeons: a critical analysis.
AB  - THREE MODELS OF CONDITIONAL DISCRIMINATION LEARNING BY PIGEONS ARE DESCRIBED:
      stimulus configuration learning, the multiple-rule model, and concept learning. A
      review of the literature reveals that true concept learning is not characteristic
      of the behavior of pigeons in matching-to-sample, oddity-from-sample, or symbolic
      matching studies. Instead, pigeons learn a set of sample-specific S(D) rules.
      Transfer of the discrimination to novel stimuli, at least along the hue
      dimension, is predicted by a "coding hypothesis", which holds that pigeons make a
      unique, but usually unobserved response, R(1), to each sample, and that the
      comparison stimulus chosen depends on which R(1) was emitted in the presence of
      the sample. Convincing evidence is found that pigeons do code sample hues, but
      there is little evidence that allows one to infer that the "coding event" must
      have behavioral properties. Parameters of the conditional discrimination paradigm
      are identified, and it is shown that by appropriate parametric manipulation, a
      variety of analogous tasks may be generated for both human and animal subjects.
      The tasks make possible the comparative study of complex learning, attention,
      memory, and information processing, with the added advantage that behavior
      processes may be compared systematically across tasks.

PMID- 16812080
TI  - Inhibiting function of reinforcement: magnitude effects on variable-interval
      schedules.
AB  - In two experiments, the performance of rats under constant-probability and
      arithmetic variable-interval schedules respectively was compared when the
      concentration of a liquid reinforcer was varied within sessions; in other
      sessions, half of the reinforcers were randomly omitted. When the discriminative
      function of the reinforcer as a signal for a decrease in the probability of
      reinforcement was attenuated (the constant-probability schedule) the
      postreinforcement pause duration was nevertheless an increasing function of
      reinforcer magnitude. This relationship was also present, but more marked, when
      the temporal discriminative function of the reinforcer was enhanced (the
      arithmetic schedule). These results suggested that reinforcement has an
      unconditioned suppressive effect on the reinforced response distinct from any
      discriminative function it may acquire. The reinforcement-omission effect, where
      response rate accelerates following omission, was observed when the reinforcer
      functioned as an effective temporal discriminative stimulus, but not when such
      temporal control was absent.

PMID- 16812081
TI  - Contrast and autoshaping in multiple schedules varying reinforcer rate and
      duration.
AB  - Thirteen master pigeons were exposed to multiple schedules in which reinforcement
      frequency (Experiment I) or duration (Experiment II) was varied. In Phases 1 and
      3 of Experiment I, the values of the first and second components' random-interval
      schedules were 33 and 99 seconds, respectively. In Phase 2, these values were 99
      seconds for both components. In Experiment II, a random-interval 33-second
      schedule was associated with each component. During Phases 1 and 3, the first and
      second components had hopper durations of 7.5 and 2.5 seconds respectively.
      During Phase 2, both components' hopper durations were 2.5 seconds. In each
      experiment, positive contrast obtained for about half the master subjects. The
      rest showed a rate increase in both components (positive induction). Each master
      subject's key colors and reinforcers were synchronously presented on a response
      independent basis to a yoked control. Richer component key-pecking occurred
      during each experiment's Phases 1 and 3 among half these subjects. However, none
      responded during the contrast condition (unchanged component of each experiment's
      Phase 2). From this it is inferred that autoshaping did not contribute to the
      contrast and induction findings among master birds. Little evidence of local
      contrast (highest rate at beginning of richer component) was found in any
      subject. These data show that (a) contrast can occur independently from
      autoshaping, (b) contrast assays during equal-valued components may produce
      induction, (c) local contrast in multiple schedules often does not occur, and (d)
      differential hopper durations can produce autoshaping and contrast.

PMID- 16812082
TI  - Choice in a "self-control" paradigm: effects of a fading procedure.
AB  - Pigeons chose between an immediate 2-second reinforcer (access to grain) and a 6
      second reinforcer delayed 6 seconds. The four pigeons in the control group were
      exposed to this condition initially. The four experimental subjects first
      received a condition where both reinforcers were delayed 6 seconds. The small
      reinforcer delay was then gradually reduced to zero over more than 11,000 trials.
      Control subjects almost never chose the large delayed reinforcer. Experimental
      subjects chose the large delayed reinforcer significantly more often. Two
      experimental subjects showed preference for the large reinforcer even when the
      consequences for pecking the two keys were switched. The results indicate that
      fading procedures can lead to increased "self-control" in pigeons in a choice
      between a large delayed reinforcer and a small immediate reinforcer.

PMID- 16812083
TI  - Fading and errorless transfer in successive discriminations.
AB  - A successive discrimination between red positive and green negative stimuli was
      established with pigeon subjects. Then, lines with different angular orientations
      were superimposed on one of the colors to form compound stimuli. Finally, either
      the colored element of the positive compound, the colored element of the negative
      compound, or both colored elements together, were gradually attenuated. Before
      each attenuation, the line elements were presented alone against dark backgrounds
      as probes to assess the degree to which they had acquired control of responding.
      When the positive color was attenuated alone or in conjunction with the negative
      color, angular orientation acquired control of responding in an errorless
      fashion. Lines, however, did not acquire control when only the negative component
      was attenuated. These results were interpreted in terms of changes in the
      predictability of reinforcement by color and line elements during stimulus
      attenuation. Finally, attenuation of the negative stimulus influenced the number
      of "dimensions" of the new line stimuli that acquired control of responding. When
      the positive stimulus was attenuated with the negative, only one dimension of the
      lines acquired control. When the positive stimulus was attenuated without the
      negative, however, more than one dimension of the lines acquired control of
      responding. These results were interpreted in terms of how errorless performance
      can be maintained while an organism attends to different dimensions of the new
      stimuli.

PMID- 16812084
TI  - The effect of foreperiod duration on reaction time and its relation to interval
      schedules of reinforcement.
AB  - Two groups of pigeons were exposed to a simple reaction-time procedure in which
      mean foreperiod duration was 5, 10, or 20 seconds. For one group, the foreperiods
      had an arithmetic, or rectangular, distribution; for the second group, they had a
      constant-probability, or Bernoulli, distribution. Under both distributions, mean
      response latency was an increasing, negatively accelerated function of mean
      foreperiod duration. On a given trial, response latency was a function of its
      associated foreperiod duration: latency was a decreasing function of foreperiod
      duration in the arithmetic distribution, and an increasing function of foreperiod
      duration in the constant-probability distribution. Examination of the
      distribution of latencies revealed a harmonic structure reminiscent of
      distributions of interresponse times under variable-interval schedules of
      reinforcement. Taken together, the results confirm and extend previous findings
      with human subjects, and also suggest numerous similarities to behavior
      maintained by variable-interval schedules.

PMID- 16812085
TI  - Performance of rats under concurrent variable-interval schedules of negative
      reinforcement.
AB  - The behavior of rats under concurrent variable-interval schedules of negative
      reinforcement was examined. A single one-minute variable-interval programmer
      determined the availability of 30-second timeouts from electric shock. These were
      assigned to one or the other of the two component schedules with a probability of
      0 to 1.0. The response requirement for the component schedules was standing to
      the right or left of the center of the experimental chamber. With a six-second
      changeover delay, the relative time spent under one component schedule varied
      directly and linearly with the relative number of timeouts earned under that
      component schedule. The absolute number of changeovers was highest when a similar
      number of timeouts was earned under each component schedule, and lowest when all
      or nearly all timeouts were earned under one component schedule. In general,
      these relations are similar to those reported with concurrent variable-interval
      schedules of positive reinforcement.

PMID- 16812086
TI  - Automaintenance in guinea pigs: effects of feeding regimen and omission training.
AB  - Behavior maintained by stimulus-reinforcer pairings was examined. Guinea pigs
      maintained at 85 per cent of free-feeding weights reliably contacted a
      retractable lever presented before delivery of a single piece of guinea-pig chow
      or a 45-milligram guinea-pig pellet. When animals were given free access to one
      food and received the second food preceded by the lever, contact responses
      persisted. Such responses seldom occurred when a single food was freely available
      and was also delivered after lever presentation. Introduction of an omission
      training (negative automaintenance) procedure, in which lever contacts resulted
      in lever retraction and prevented food delivery, strongly reduced lever contacts.
      Observation indicated that mouthing the food cup, instead of the lever, became
      the prominent behavior during the prefood stimulus under the omission training
      procedure.

PMID- 16812087
TI  - Variable shock-free times with informative and uniformative stimuli.
AB  - Three rats were trained on a fixed-ratio escape procedure in which responding
      produced one of two equiprobable outcomes-a 10-second or 60-second shock-free
      period. Before the fixed-ratio requirement was satisfied, brief shocks were
      presented at irregular intervals averaging either 15 or 30 seconds. Two
      conditions, differing in the relationship between exteroceptive stimuli and the
      outcomes, were studied. In the uninformative (uncorrelated) condition, the same
      stimulus was presented during both outcomes. In the informative (correlated)
      condition, one stimulus was present during the 10-second outcome only; another
      stimulus was present during the 60-second outcome only. Subjects pressed faster
      in the uninformative condition than they did in the informative condition. The
      inadequacy of the information hypothesis in accounting for the findings is
      discussed, and an alternative hypothesis is offered.

PMID- 16812088
TI  - Contrast and induction in multiple schedules of discrete-trial concurrent
      reinforcement.
AB  - Three pigeons were exposed to two-key discrete-trial concurrent schedules of
      reinforcement. Red and white key colors alternated irregularly and the assignment
      of reinforcers depended on key color. The red-key schedules were held constant,
      with the scheduled relative frequency of reinforcement for left-key pecks set at
      0.75, while the white-key schedules varied. When the location of white-key
      reinforcement was changed from one side to the other, while its overall frequency
      was constant, red-key choices shifted in the same direction as white-key choices,
      an induction effect. When the overall frequency of white-key reinforcement was
      changed while its location remained constant, red key choices shifted in a
      direction opposite to white-key choices, a contrast effect. Both induction and
      contrast effects were clearer when the overall frequency of red-key reinforcement
      was reduced. These data demonstrate that the allocation of responding may exhibit
      schedule interaction effects similar to those commonly reported for response
      rate.

PMID- 16812089
TI  - Variability of response location on fixed-ratio and fixed-interval schedules of
      reinforcement.
AB  - Variability of response location was studied in monkeys performing in a six-lever
      chamber. Fixed-ratio schedules, ranging from FR 1 to FR 300, generated a high
      degree of stereotypy of response location. In contrast, fixed-interval schedules
      of comparable reinforcement frequencies (0.06 to 4 minutes) generated much
      greater variability. These results failed to confirm any simple relationship
      between response variability and intermittence of reinforcement. Rather,
      variability seems to be determined by the particular characteristics of the
      reinforcement schedule.

PMID- 16812090
TI  - Discriminability of fixed-ratio schedules for pigeons: effects of payoff values.
AB  - Three pigeons, previously trained to discriminate different numbers of responses
      (fixed ratios), were tested under different reinforcement contingencies (payoff
      matrices) at two levels of sensitivity. For one subject, relative reinforcement
      magnitude was varied-at first, across sessions and then, at midsession by
      reversing values-without exteroceptive cues. For another, relative reinforcement
      magnitude and/or probability was varied every 50 trials with cues by correlating
      different payoff matrices with different key colors. For the third subject,
      relative reinforcement probability was varied more frequently with cues-in the
      limit, at random-to demonstrate stimulus control of response bias on a trial-by
      trial basis. A signal-detection analysis showed that bias changed with payoffs,
      for as many as seven different matrices, while sensitivity remained unchanged.
      The obtained functions (receiver operating characteristics) were similar under
      different payoff conditions, which suggests that a single mechanism controls
      bias. However, they differed enough in slope to require a relatively complex
      account (e.g., the general Gaussian model of detection theory).

PMID- 16812091
TI  - Diversity and substitutability of adjunctive activities under fixed-interval
      schedules of food reinforcement.
AB  - Six rats received food contingent on pressing a lever on fixed-ratio 1, fixed
      interval 30-second, and fixed-interval 60-second schedules, with concurrent
      access to a drinking spout, a running wheel, and a block of wood. Drinking,
      running, and chewing were monitored automatically, and these and other activities
      were observed directly during selected sessions. Because all sessions ended after
      delivery of 60 pellets, total time available for activities other than eating
      increased over the three schedules. Time spent contacting the lever and visiting
      the food tray increased in proportion to total available time, whereas the time
      spent in other activities changed in a complex manner such that drinking was the
      dominant adjunctive behavior in the 30-second condition, and running or chewing
      the dominant adjunctive behavior in five of six rats in the 60-second condition.
      General activity and grooming also occupied significant amounts of time. In a
      subsequent part of the experiment, running and chewing were prevented, and the
      majority of other activities, especially drinking and grooming, increased. The
      results show that (a) FI schedules of food reinforcement are accompanied by a
      wide variety of adjunctive activities; (b) the preferred activity differs
      according to the schedule duration; and (c) the extent to which activities
      substitute for one another is limited by the tendency for different activities to
      occupy different parts of the interreinforcement interval.

PMID- 16812092
TI  - Visual dominance in the pigeon.
AB  - In Experiment 1, three pigeons were trained to obtain grain by depressing one
      foot treadle in the presence of a 746-Hertz tone stimulus and by depressing a
      second foot treadle in the presence of a red light stimulus. Intertrial stimuli
      included white light and the absence of tone. The latencies to respond on
      auditory element trials were as fast, or faster, than on visual element trials,
      but pigeons always responded on the visual treadle when presented with a compound
      stimulus composed of the auditory and visual elements. In Experiment 2, pigeons
      were trained on the auditory-visual discrimination task using as trial stimuli
      increases in the intensity of auditory or visual intertrial stimuli. Again,
      pigeons showed visual dominance on subsequent compound stimulus test trials. In
      Experiment 3, on compound test trials, the onset of the visual stimulus was
      delayed relative to the onset of the auditory stimulus. Visual treadle responses
      generally occurred with delay intervals of less than 500 milliseconds, and
      auditory treadle responses generally occurred with delay intervals of greater
      than 500 milliseconds. The results are discussed in terms of Posner, Nissen, and
      Klein's (1976) theory of visual dominance in humans.

PMID- 16812093
TI  - Schedule-induced drinking as functions of interpellet interval and draught size
      in the Java macaque.
AB  - Three Java monkeys received food pellets that were assigned by both ascending and
      descending series of fixed-time schedules whose values varied between 8 and 256
      seconds. The draught size dispensed by a concurrently available water-delivery
      tube was systematically varied between 1.0 and 0.3 milliliter per lick at various
      fixed-time values during the second and third series determinations. Session
      water intake was bitonically related to the interpellet interval and was
      determined by the interaction of (1) the probability of initiating a drinking
      bout, which fell off at the highest interpellet intervals and, (2) the size of
      the bout, which increased directly with increases in interpellet interval.
      Variations in draught size had little effect on total session intakes, but
      reduced bout size at draught sizes of 0.5 milliliter and below. Thus, a volume
      regulation process of schedule-induced drinking operated generally at the session
      intake level, but was limited to higher draught sizes at the bout level.

PMID- 16812094
TI  - Temporal factors influencing the pigeon's successive matching-to-sample
      performance: sample duration, intertrial interval, and retention interval.
AB  - A successive matching-to-sample procedure that entails the sequential
      presentation of sample and test stimuli and the monitoring of response rates in a
      go/no-go discrimination of matching and nonmatching stimuli was studied as an
      alternative to the familiar delayed-matching paradigm of animal short-term
      memory. Three within-subject experiments studied the effects of sample duration
      (1 to 12 seconds), intertrial interval (5 to 50 seconds), and retention interval
      (1 to 50 seconds) on the pigeon's successive-matching performance. The results
      revealed that retention was (a) an increasing function of sample duration and
      intertrial interval, and (b) a decreasing function of retention interval. These
      results were in accord with those of more traditional short-term memory
      paradigms, and reveal the suitability of the successive-matching procedure for
      studying memory processes.

PMID- 16812095
TI  - Reaction times of pigeons on a wavelength discrimination task.
AB  - After extensive pretraining, three pigeons were exposed in 2-second trials to a
      random series of 14 light wavelengths, ranging in one nanometer (nm) steps from
      575 nanometers to 589 nanometers. Responses to one of the wavelengths, 582
      nanometers, were intermittently reinforced. The relative frequency of response
      approached 1.0 at 582 nanometers, and decreased with progressively higher and
      lower wavelengths. Reaction times shorter than about 0.2 second occurred with a
      low frequency that was largely independent of wavelength. Wavelength controlled
      the frequency of longer reaction times, but did not affect the distribution of
      these reaction times. Consequently, receiver-operating characteristic curves
      constructed by using reaction time as a rating measure did not conform to the
      signal-detection model, in contrast to such conformity when response rate is used
      in a similar way. The data suggest that stimulus onset as such triggers early
      response emission with some small probability; the probability of responses with
      longer latency is controlled by wavelength, but their time of emission is
      controlled by some independent process.

PMID- 16812096
TI  - Unsignalled delay of reinforcement in variable-interval schedules.
AB  - Three pigeons responded on several tandem variable-interval fixed-time schedules
      in which the value of the fixed-time component was varied to assess the effects
      of different unsignalled delays of reinforcement. Actual (obtained) delays
      between the last key peck in an interval and reinforcement were consistently
      shorter than the nominal (programmed) delay. When nominal delays were relatively
      short, response rates were higher during the delay condition than during the
      corresponding nondelay condition. At longer nominal delay intervals, response
      rates decreased monotonically with increasing delays. The results were consistent
      with those obtained from delay-of-reinforcement procedures that impose either a
      stimulus change (signal) or a no-response requirement during the delay interval.

PMID- 16812097
TI  - Same/different concept learning in the pigeon: the effect of negative instances
      and prior adaptation to transfer stimuli.
AB  - Pigeons were trained on a matching-to-sample or oddity-from-sample task with
      shapes (circle and plus). Half of each group was exposed to "negative instance"
      trials i.e., for matching birds, neither comparison key matched the sample, and
      for oddity birds both comparison keys matched the sample. When all birds were
      transferred to a new task involving colors (red and green), nonshifted birds
      (transferred from matching to matching, or oddity to oddity) performed
      significantly better than shifted birds (transferred from matching to oddity, or
      oddity to matching), but only if they had experienced negative instances of the
      training concept. When all birds were exposed to negative instances of the
      transfer task and then transferred to a new color task (yellow and blue),
      dramatic transfer effects were observed. The effect of pre-exposure to the yellow
      and blue colors, in order to reduce transfer-stimulus novelty, had a minor effect
      on transfer.

PMID- 16812098
TI  - A clarification of continuous repertoire development.
AB  - The key-peck response of five pigeons was reinforced on a schedule whenever the
      interval between pecks at two response keys was between 1.0 and 2.33 seconds in
      the presence of a 2,500-Hertz tone or between 4.66 and 6.0 seconds in the
      presence of a 1250-Hertz tone. There was no tendency for responses of
      intermediate duration to occur when test tones of intermediate frequency were
      presented. This result clarifies a previous finding using a similar procedure but
      with a visual intensity stimulus dimension.

PMID- 16812099
TI  - The nature of standard control in children's matching-to-sample.
AB  - In Experiment I, six preschool-aged children were given matching-to-sample
      training with two figures in which they were required to choose one of two
      comparison stimuli that was identical in shape to the standard stimulus.
      Following this training, they were given intermittent test trials in which a
      novel stimulus figure was substituted for the previously correct comparison
      stimulus. Five of the six subjects consistently chose the substituted stimulus
      during test trials. Experiment II replicated the findings of Experiment I with
      three other preschool-aged children. Experiment II also provided controls for the
      possibility that the subjects of Experiment I were selecting the substituted
      stimulus because of its novelty. The investigators concluded that eight of the
      nine subjects were exhibiting the type of control described by Berryman, Cumming,
      Cohen, and Johnson (1965) as S-delta responding.

PMID- 16812100
TI  - A procedure for studying echoic control in verbal behavior.
AB  - Male and female college students answered standard questions about the women's
      liberation movement on three occasions. A set of target words was embedded in the
      questions, with one set used in Sessions 1 and 3, and a synonymous, but different
      set used in Session 2. The relative frequencies of usage of a given target word
      were directly related to whether the questions for that session contained the
      word. The results supported the hypothesis of echoics as proposed in Skinner's
      theory of verbal behavior.

PMID- 16812101
TI  - Second-order schedules of token reinforcement: comparisons of performance under
      fixed-ratio and variable-ratio exchange schedules.
AB  - Rats' lever pressing produced tokens according to a 20-response fixed-ratio
      schedule. Sequences of token schedules were reinforced under a second-order
      schedule by presentation of periods when tokens could be exchanged for food
      pellets. When the exchange period schedule was a six-response fixed ratio,
      patterns of completing the component token schedules were bivalued, with
      relatively long and frequent pauses marking the initiation of each new sequence.
      Altering the exchange period schedule to a six-response variable ratio resulted
      in sharp reductions in the frequency and duration of these initial pauses, and
      increases in overall rates of lever pressing. These results are comparable to
      those ordinarily obtained under simple fixed-ratio and variable-ratio schedules.

PMID- 16812102
TI  - Matching with a key-peck response in concurrent negative reinforcement schedules.
AB  - In the absence of responding, pigeons were shocked under a variable-time
      schedule. Responses on either of two keys occasionally produced one minute of
      shock-free time. That is, pigeons' key pecks were reinforced with shock-free time
      under concurrent variable-interval schedules. The relative frequency of access to
      the one-minute shock-free periods was systematically manipulated. Pigeons tended
      to match both relative response rate and proportion of time spent on each key to
      the relative frequency of the shock-free periods. A best-fit linear regression
      equation accounted for over 95% of the variance in both relative response rate
      and time allocation. The data paralleled closely the results of concurrent
      schedules of positive reinforcement. These findings are consistent with a
      description of reinforcement as a transition to a higher-valued situation and
      suggest that common laws govern choice for both positive and negative
      reinforcement.

PMID- 16812103
TI  - Delayed reinforcement of fixed-ratio performance without mediating exteroceptive
      conditioned reinforcement.
AB  - The performance of pigeons was studied under conditions in which the completion
      of a fixed-ratio requirement was not contiguous with the presentation of a
      reinforcer. Timein and timeout periods alternated throughout the experimental
      sessions. Responses made by an experimental bird during the timein period were
      accumulated, and when a fixed-ratio requirement had been met, grain was presented
      to the experimental bird and a yoked control following their first response in
      the next timein period. Across most manipulations of the fixed-ratio requirement
      and of the duration of the timeout period, the response rates of the experimental
      birds were considerably higher than those of their controls, suggesting that the
      response-reinforcer dependency controlled the behavior of the experimental bird
      in the absence of a close temporal association between responding on the ratio
      schedule and reinforcer presentations.

PMID- 16812104
TI  - Multiple schedule component duration: a reanalysis of Shimp and Wheatley (1971)
      and Todorov (1972).
AB  - The tendency for relative response rate to approach matching as multiple schedule
      component duration decreases has been interpreted as confirming a prediction of
      Herrnstein's multiple schedule equation. However, the equation predicts that
      absolute response rate will decrease in both multiple schedule components as
      component duration decreases. The absolute response-rate data of two studies of
      component duration do not support this prediction; absolute rate either increased
      or remained relatively constant.

PMID- 16812105
TI  - Reinforcement and substitution in humans: a multiple-response analysis.
AB  - Three adult human subjects engaged in activities such as reading, sewing,
      artwork, and candlemaking while living alone in a laboratory apartment 24 hours
      per day for several weeks. After a baseline period in which the activities were
      fully available, access to a particular activity (contingent response) was made
      dependent on engaging in another less-preferred activity (instrumental response).
      The contingencies produced substantial increases in instrumental responding, and
      responding decreased toward baseline levels when the dependency was removed.
      Under the contingent conditions, time earned for the concurrent activity was
      always less than the baseline level. To determine the contribution of this
      reduction to the instrumental increase, access to the contingent activity was
      restricted in the absence of any dependency. The results indicated that increases
      among responses that filled the newly available time could be selective, e.g.,
      artwork increased when reading was restricted but candlemaking did not. It was
      concluded that the reductions in the contingent response that accompany
      contingencies usually do not exclusively determine instrumental increases, but
      selective increases can contribute to the increase in time devoted to the
      instrumental response.

PMID- 16812106
TI  - Temporal control of behavior: schedule interactions.
AB  - In Experiment I the response that terminated the postreinforcement pauses
      occurring under a fixed-interval 60-second schedule was reinforced, if the pause
      duration exceeded 30 seconds. The percentage of such pauses, rather than
      increasing, decreased. There were complex effects on the discriminative control
      of the pause by the reinforcer terminating the previous fixed interval, depending
      on whether the fixed interval and the added reinforcer were the same or
      different. In Experiments II(a) and II(b), each reinforcement initiated an
      alternative fixed-interval interresponse-time-greater-than-t-sec schedule, the
      schedule values being systematically varied. When the response following a pause
      exceeding a given duration was reinforced, fewer such pauses occurred than when
      they were not reinforced, i.e., on the comparable simple fixed-interval schedule.
      There was no systematic relationship between mean interrinforcement interval and
      duration of the postreinforcement pause. The pause duration initiated by
      reinforcement was directly related to the dependency controlling the shortest
      pause at that time, regardless of changes in mean interreinforcement interval.

PMID- 16812107
TI  - Responding maintained under fixed-interval and fixed-time schedules of electric
      shock presentation.
AB  - Following initial histories under a schedule of electric shock postponement,
      lever pressing in squirrel monkeys was maintained under fixed-interval and fixed
      time schedules of electric shock presentation. No difference in either rate or
      pattern of responding was obtained when these schedules were presented as
      components of a multiple schedule. When they were presented singly for long
      periods of time, the fixed-interval schedule consistently maintained a higher
      response rate than the fixed-time schedule. The pattern of responding under both
      schedules was similar, typically consisting of a pause at the beginning of each
      interval followed by either a steady or a positively accelerating rate of
      responding. The results suggest that the response-shock dependency is of critical
      importance in the maintenance of high rates of responding under schedules of
      electric shock presentation, and support the general view that such responding
      may be conceptualized as operant behavior under control of many of the same
      variables that control responding under comparable schedules of food or water
      reinforcement.

PMID- 16812108
TI  - Warmup in free-operant avoidance as a function of the response-shock = shock
      shock interval.
AB  - Warmup effects, the repeated within-session transitions from ineffective to
      effective avoidance, were examined with rats on free-operant shock-delay
      procedures. The shock-shock and response-shock intervals were kept equal as they
      were varied. As measured by both response rates and shock rates, the magnitude of
      within-session change in performance was inversely related to the size of the
      manipulated intervals. The duration of warmup tended to decrease as the intervals
      were increased. This finding, that increased shock frequencies do not shorten the
      warmup, appears to be inconsistent with all interpretations of the warmup that
      have been offered to date. Late-session performances replicated general features
      of prior experiments, but differed with respect to details of secondary
      conclusions in previous reports. These differences may stem from the selection of
      especially proficient avoiders for previous experiments.

PMID- 16812109
TI  - Avoidance based on shock intensity reduction with no change in shock probability.
AB  - Rats were trained on a free-operant avoidance procedure in which shock intensity
      was controlled by interresponse time. Shocks were random at a density of about 10
      shocks per minute. Shock probability was response independent. As long as
      interresponse times remained less than the limit in effect, any shocks received
      were at the lower of two intensities (0.75 mA). Whenever interresponse times
      exceeded the limit, any shocks received were at the higher intensity (1.6 mA).
      The initial limit of 15 seconds was decreased in 3-second steps to either 6 or 3
      seconds. All animals lever pressed to avoid higher intensity shock. As the
      interresponse time limit was reduced, the response rate during the lower
      intensity shock and the proportion of brief interresponse times increased.
      Substantial warmup effects were evident, particularly at the shorter
      interresponse-time limits. Shock intensity reduction without change in shock
      probability was effective in the acquisition and maintenance of avoidance
      responding, as well as in differentiation of interresponse times. This research
      suggests limitations on the generality of a safety signal interpretation of
      avoidance conditioning.

PMID- 16812110
TI  - Concurrent random-interval schedules and the matching law.
AB  - In Experiment I, a group of eight pigeons performed on concurrent random-interval
      schedules constructed by holding probability equal and varying cycle time to
      produce ratios of reinforcer densities of 1:1, 3:1, and 5:1 for key pecking.
      Schedules for a second group of seven were constructed with equal cycle times and
      unequal probabilities. Both groups deviated from simple matching, but the two
      forms of the schedules appeared to produce no consistent patterns of deviation.
      The data were found to be consistent with those obtained in concurrent variable
      interval situations. The parameters of the matching equation in the form of Y=k
      X(a) were estimated; the value of k was unity and a was 0.84. In Experiment II,
      six pigeons were exposed to two conc RI RI schedules in which one component
      increasingly approximated an FI schedule. The value of k was not 1.0. Concurrent
      RI RI schedules were shown to represent a continuum from conc FI VI to conc VI VI
      schedules. The use of the exponential equation in testing "matching laws"
      suggests that a<1 will continue to be observed, and this will set limits on the
      form of new laws and the assumed or rational values of the component variables in
      these laws.

PMID- 16812111
TI  - The relative law of effect: effects of shock intensity on response strength in
      multiple schedules.
AB  - Key pecking of four birds was reinforced with food according to a two-component
      multiple variable-interval 1-minute variable-interval 4-minute schedule. In
      addition, key pecking was punished by a brief shock according to a variable
      interval 30-second schedule during both components of the multiple schedule. The
      intensity of the shock was varied. For all birds, punishment had a stronger
      suppressive effect on the responding maintained by the leaner food schedule, and
      the ratio of responding during the two components of the multiple schedule became
      closer to the ratio of reinforcement as shock intensity was increased, as the
      relative law of effect predicts. At the higher shock intensity, there was some
      evidence that the ratio of responses overmatched the ratio of reinforcements.

PMID- 16812112
TI  - Interactions in multiple schedules: negative induction with squirrel monkeys.
AB  - In Experiment I, lever pressing by squirrel monkeys was maintained under a
      sequence of variable-interval, multiple variable-interval variable-interval, and
      multiple variable-interval extinction schedules of food presentation. Negative
      induction (decreased responding in the unchanged component) occurred when one
      component of the multiple variable-interval variable-interval schedule was
      changed to extinction. Negative induction was transient over sessions; responding
      in the unchanged component usually recovered to a rate similar to that under the
      multiple variable-interval variable-interval schedule. Negative induction was not
      accompanied by consistent changes in the patterns of local responding within the
      unchanged component, and did not depend on whether component schedules were
      associated with localized (lever lights) or diffuse visual stimuli (houselights),
      or on whether the unchanged component was a 60- or 180-sec variable-interval
      schedule. In Experiment II, responding was maintained under a sequence of
      variable-interval and multiple variable-interval timeout schedules of food
      presentation. Negative induction occurred when responding declined gradually in
      the timeout component but not when responding declined abruptly. The nature of
      interactions in multiple schedules may depend on the species; negative induction
      was observed with squirrel monkeys under conditions similar to those that produce
      positive contrast with pigeons.

PMID- 16812113
TI  - Positive conditioned suppression: an explanation in terms of multiple and
      concurrent schedules.
AB  - Rats performed under a baseline variable-interval schedule of food presentation.
      A response-independent food schedule was then superimposed on the baseline
      schedule for different periods of time across different conditions. The response
      independent schedule operated for the whole session in some conditions,
      intermittently for sixty second periods in some, and intermittently for ten
      second periods in others. Under these latter two sets of conditions, the response
      independent food schedule was stimulus correlated and alternated with the
      baseline schedule according to a multiple schedule. Response-independent food
      presentations always suppressed responding. The degree of suppression tended to
      increase the longer the period of response-independent food. Control conditions,
      in which the superimposed schedule was response-dependent, rather than response
      independent, did not produce response suppression. The results fit an analysis of
      positive conditioned suppression phenomena in the context of multiple and
      concurrent schedule effects.

PMID- 16812114
TI  - A molar theory of reinforcement schedules.
AB  - Behavior of subjects exposed to concurrent and individual interval and ratio
      schedules of reinforcement may be described in terms of a set of expressions
      relating the value of responses to their durations, a feedback equation relating
      reinforcement to response duration, and the assumption that subjects allocate
      their time among various responses so as to maximize value.

PMID- 16812116
TI  - Signal-controlled responding.
AB  - Pigeons' key pecks were reinforced with grain, then extinguished. An 8-second
      tone preceded the availability of peck-dependent grain 1 second after tone
      offset. When a tone signalled grain and an 8-second clicking sound did not, three
      pigeons pecked during a high percentage of tone periods, but they pecked during a
      low percentage of click periods. When the roles of the tone and clicking sound
      were reversed, performance reversed. For other birds, when a key peck during the
      tone cancelled the availability of grain (omission procedure), the tendency to
      key peck during the tone decreased some, but still remained high. A third group
      of pigeons received the omission procedure with the addition that the tone could
      not end unless 2 seconds had elapsed without a key peck. The pigeons continued to
      respond in a high percentage of tone periods. The experiments favor an
      explanation based on the pairing of the tone with a reinforced response, such as
      Pavlovian conditioning.

PMID- 16812115
TI  - Discriminated response and incentive processes in operant conditioning: a two
      factor model of stimulus control.
AB  - Understanding stimulus control generated in instrumental learning requires the
      direct investigation of discriminated response and reinforcer (incentive)
      processes acquired exclusively through the response-reinforcer contingencies
      operating on complex (multicomponent) baselines. Two series of stimulus
      compounding studies accomplished this direct investigation. In one series, the
      independent variable was the relative reinforcement between schedule components;
      in the second series, it was relative response rate between components. Stimulus
      compounding tests revealed that response and incentive processes enhanced each
      other when in agreement, counteracted each other when in opposition, and produced
      intermediate results when only one factor was operating. This pattern of results
      led to the conclusion that these factors were algebraically combining and to the
      development of a response/incentive matrix reflecting these dynamics. This two
      factor analysis was extended to the peak-shift effect in stimulus generalization
      experiments and to the generation of inhibitory control. Two decades of stimulus
      compounding and peak-shift research were organized within this two-factor
      framework, extending this traditional approach to learning to active research
      areas heretofore not systematically considered in these terms.

PMID- 16812117
TI  - The ubiquity of the cumulative record: a quote from Skinner and a frequency
      count.

PMID- 16812118
TI  - A pellet feeder for the birds.
AB  - An alternative means of delivering food to pigeons in operant conditioning
      research is described. The feeder allows greater control of the amount of food
      delivered and reduces the amount of time necessary for the pigeon to collect the
      food. It is possible to extend the length of experimental sessions due to the
      reduction of food intake. Data obtained using the pellet feeder indicated that
      the control of responding is comparable to that observed with the standard grain
      magazine feeder.

PMID- 16812119
TI  - Conditioning of two-response patterns of key pecking in pigeons.
AB  - On discrete trials, two response keys were made available to hungry pigeons and
      food reinforcement depended on the order in which the required two key pecks
      occurred. In different phases, only one of the four possible two-peck sequences
      (left-left, left-right, right-left, and right-right) produced food reinforcement.
      In each case, the pigeons learned to perform the correct two-peck sequence more
      often than the incorrect sequences. Furthermore, the course of differentiation
      mastery indicated that both reinforcement history and response-reinforcer
      contiguity influenced performance. These results reveal that response patterns
      comprising two instances of the same response left-left and right-right) or
      instances of two different responses (left-right and right-left) may function as
      operants, thereby extending the generality of conditioning principles from
      discrete responses to structured sequences of behavior. These and other results
      are discussed in terms of contiguity-based and memory-based models of learning.

PMID- 16812120
TI  - Interresponse-time shaping by variable-interval-like interresponse-time
      reinforcement contingencies.
AB  - The interresponse-time reinforcement contingencies and distributions of
      interreinforcement intervals characteristic of certain variable-interval
      schedules were mimicked by reinforcing each key peck with a probability equal to
      the duration of the interresponse time it terminated, divided by the scheduled
      mean interreinforcement interval. The interresponse-time reinforcement
      contingency was then eliminated by basing the probability of reinforcement on the
      fifth interresponse time preceding the key peck. Even though distributions of
      interreinforcement intervals were unaffected by this manipulation, response rates
      consistently increased. A second experiment replicated this effect and showed it
      to combine additively with that of mean reinforcement rate. These results provide
      strong support for the contention that current analyses of variable-interval
      response rates that ignore the inherent interresponse-time reinforcement
      contingency may be seriously in error.

PMID- 16812121
TI  - Temporal distributions of responding during discrete-trial omission training in
      rats.
AB  - Within-session temporal distributions of responding were investigated in three
      experiments using rats pressing a lever in a discrete-trial omission procedure.
      This schedule entailed 60, one-minute trials, and a sucrose solution was made
      available at the end of each trial in which no lever press occurred. In
      Experiment I, nonnaive rats acquired and maintained responding during this
      training. Moreover, the probability of a response during any session showed a
      strong and reliable tendency to increase from the beginning to the end of the
      session. These results were replicated in Experiment II, using naive animals. In
      Experiment III, alterations were made in the training procedure, including
      elimination of response-contingent and noncontingent stimulus changes. Results
      indicate that stimulus change may be sufficient to maintain low levels of
      responding whether or not this change is contingent on responding.

PMID- 16812122
TI  - A Markov model description of changeover probabilities on concurrent variable
      interval schedules.
AB  - The primary data were peck-by-peck sequential records of four pigeons responding
      on several different concurrent variable-interval schedules. According to the
      hypothesis that the subject chooses the alternative with the highest probability
      of reinforcement at the moment, response-by-response performance in concurrent
      schedules should show sequential dependencies. However, such dependencies were
      not found, and it was possible to describe molecular-level performance with
      simple Markov chain models. The Markov model description implies that the
      momentary changeover probabilities were proportional to the overall relative
      reinforcement frequencies, and that changeover probabilities did not change as a
      function of previous responding. A second finding was that although a changeover
      delay procedure was omitted, relative response frequencies closely approximated
      relative reinforcement frequencies.

PMID- 16812123
TI  - Contingency-shaped and rule-governed behavior: instructional control of human
      loss avoidance.
AB  - Instructions can override the influence of programmed schedules of reinforcement.
      Although this finding has been interpreted as a limitation of reinforcement
      schedule control in humans, an alternative approach considers instructional
      control, itself, as a phenomenon determined by subjects' reinforcement histories.
      This approach was supported in a series of experiments that studied instructional
      and schedule control when instructions either did or did not accord with the
      schedule of reinforcement. Experiment I demonstrated that accurate instructions
      control discriminative performances on multiple avoidance schedules, and that
      such control persists in a novel discrimination. Experiments II and III showed
      that elimination of instruction-following occurs when inaccurate instructions
      cause subjects to contact a monetary loss contingency. Experiment IV demonstrated
      the reinforcing properties of accurate instructions. Skinner's view of rule
      governed behavior is consistent with these findings, and can be extended to
      account for many aspects of instructional control of human operant behavior.

PMID- 16812124
TI  - The effect of punishment on free-operant choice behavior in humans.
AB  - During Phase I, three female human subjects pressed a button for monetary
      reinforcement in five variable-interval schedules specifying different
      frequencies of reinforcement. On alternate days, responding was also punished (by
      subtracting money) according to a variable-ratio 34 schedule. In the absence of
      punishment, response rates conformed to Herrnstein's equation for single variable
      interval schedules. Punishment suppressed responding at all frequencies of
      reinforcement. This was reflected in a change in the values of both constants in
      Herrnstein's equation: the value of the theoretical maximum response-rate
      parameter was reduced, and the parameter describing the reinforcement frequency
      corresponding to the half-maximal response rate was elevated. During Phase II,
      the same five schedules (A) were in operation (without punishment), but in
      addition, a concurrent variable-interval schedule (B) of standard reinforcement
      frequency was introduced. On alternate days, responding in Component B was
      punished according to a variable-ratio 34 schedule. In the absence of punishment,
      absolute response rates conformed to equations proposed by Herrnstein to describe
      performance in concurrent schedules; the ratios of the response rates in the two
      components and the ratios of the times spent in the two components conformed to
      the Matching Law. When responding in Component B was punished, response rates in
      Component B were reduced and those in Component A were elevated, these changes
      being reflected in distortions of the matching relationship.

PMID- 16812125
TI  - Food delivery as a conditional stimulus: Feature-learning and memory in pigeons.
AB  - Three experiments investigated the learning and memory of discriminations based
      on presence versus absence of a pre-trial food delivery. In Experiment 1 half the
      illuminations of a response key were followed by food regardless of the subject's
      behavior. In one group an extra food delivery preceded only reinforced trials
      (feature-positive condition), whereas in a second group it preceded only
      nonreinforced trials (feature-negative condition). Key pecks and approaches
      revealed more rapid and superior discrimination learning in the first group.
      Experiment 2 replicated the results of Experiment 1 but yielded no evidence that
      greater "unexpectedness" of pretrial food conditions facilitates discriminative
      performance. In Experiment 3, individual pigeons trained on a conditional
      discrimination exhibited a within-subject feature-positive superiority. Delay
      between pretrial and trial stimuli interacted with feature-positive versus
      feature-negative training in both the between-group (Experiment 2) and within
      subject (Experiment 3) procedures: performance was decremented at both short and
      long delays in the feature-positive condition but was decremented only at longer
      delays in the feature-negative condition. The feature-positive superiority
      obtained here is incompatible with explanations based on either the general
      concept of "perceptual organization" or on the conditional nature of feature
      negative discriminations.

PMID- 16812126
TI  - Is matching compatible with reinforcement maximization on concurrent variable
      interval variable ratio?
AB  - Four pigeons on concurrent variable interval, variable ratio approximated the
      matching relationship with biases toward the variable interval when time spent
      responding was the measure of behavior and toward the variable ratio when
      frequency of pecking was the measure of behavior. The local rates of responding
      were consistently higher on the variable ratio, even when there was overall
      preference for the variable interval. Matching on concurrent variable interval,
      variable ratio was shown to be incompatible with maximization of total
      reinforcement, given the observed local rates of responding and rates of
      alternation between the schedules. Furthermore, it was shown that the subjects
      were losing reinforcements at a rate of about 60 per hour by matching rather than
      maximizing.

PMID- 16812127
TI  - Concurrent ratio schedules: Fixed vs. variable response requirements.
AB  - Rats were trained on concurrent fixed-ratio variable-ratio or concurrent fixed
      ratio mixed-ratio schedules of food reinforcement. The variable-ratio schedule
      was composed of an arithmetic sequence of 11 ratios that averaged 50; the mixed
      ratio schedule consisted of equiprobable ratios of 1 and 99. Fixed-ratio values,
      varied over experimental conditions, included 25, 35, 50, 60, and 99. The
      proportion of responses and time allocated to the variable- or mixed-ratio
      schedule increased as the size of the fixed ratio increased. For most subjects,
      higher proportions of responses and time were maintained on the fixed-ratio
      schedule at fixed-ratio values of 25 and 35; higher proportions of responses and
      time were maintained on the variable- or mixed-ratio schedule at fixed-ratio
      values of 50 or higher. On concurrent variable-ratio fixed-ratio schedules, the
      tendency for responding to be maintained exclusively by one schedule was related
      to the difference in local reinforcement rates obtained from those schedules.
      Exclusive responding was approximated when the difference in local reinforcement
      rates obtained from those schedules was large; responding was more evenly
      distributed between the schedules as the difference in the rates at which
      reinforcement was obtained from each decreased.

PMID- 16812128
TI  - Changeover ratio effects on concurrent variable-interval performance.
AB  - Rats' bar-pressing was maintained by concurrent variable-interval schedules of
      reinforcement. A fixed-ratio of pulls on a chain (the changeover ratio) was
      required for switching between schedules. The first experiment employed equal
      variable-interval schedules and symmetrical changeover ratios. Increasing these
      ratios resulted in a decrease in the rate of switching between schedules and an
      increase in local response rate. In the second experiment, a range of
      asymmetrical changeover ratios was used with equal variable-interval schedules,
      and a preference was found for the schedule associated with the larger switching
      into ratio. Both the distributions of responses and time between the two
      schedules deviated from those expected on the basis of obtained reinforcers. In
      the third experiment, the switching-out-of ratio was dependent on the amount of
      time spent in a variable-interval 2-minute schedule; a constant ratio permitted
      switching out of the alternative variable-interval 1-minute schedule. A strong
      preference was shown for the variable-interval 2-minute schedule. The fourth
      experiment used equal variable-interval schedules; one changeover ratio was
      varied while the second remained constant. The results failed to show systematic
      differences in local response rates immediately after a changeover.

PMID- 16812129
TI  - The effects of number of responses on the postreinforcement pause in fixed
      interval schedules.
AB  - The present study manipulated the number of responses in a modified fixed
      interval schedule by imposing a blackout after each unreinforced response during
      the interval. The blackout duration was varied, and the duration of the fixed
      interval was held constant. The subjects were initially exposed to a fixed
      interval 300-sec schedule. Blackout durations of 0, 10, and 50 sec were used.
      Following this, a fixed-interval 30-sec schedule was used with blackout durations
      of 0, 1, and 5 sec. Under the fixed-interval 300-sec schedule, the number of
      interreinforcement responses varied over a wider range than occurred under the
      fixed-interval 30-sec schedule. The duration of the postreinforcement pause
      decreased as blackout durations were increased and number of responses decreased
      on the fixed-interval 300-sec schedule, but pause length did not vary with
      changes in blackout duration and number of responses for the fixed-interval 30
      sec schedule. The differences in the effects of blackout duration and response
      manipulation on the two fixed-interval schedules were attributed to relatively
      greater changes in the number of interreinforcement responses for the fixed
      interval 300-sec schedule.

PMID- 16812130
TI  - A multivariate rate equation for variable-interval performance.
AB  - A value-like parameter is introduced into a rate equation for describing variable
      interval performance. The equation, derived solely from formal considerations,
      expresses rate of responding as a joint function of rate of reinforcement and
      "reinforcer power." Preliminary tests of the rate equation show that it handles
      univariate data as well as Herrnstein's hyperbola. In addition, a form of
      Herrnstein's hyperbola can be derived from the equation, and it predicts forms of
      matching in concurrent situations. For the multivariate case, reinforcer values
      scaled in concurrent situations where matching is assumed to hold are taken as
      determinations of reinforcer power. The multivariate rate equation is fitted to
      an appropriate set of data and found to provide a good description of variable
      interval performance when both rate and power of reinforcement are varied. Rate
      and power measures completely describe reinforcement. The effects of their joint
      variation are not predicted and cannot be described by Herrnstein's equation.

PMID- 16812131
TI  - A direct fluid delivery system for the pigeon.

PMID- 16812132
TI  - Suggested Greek translations of expressions in the experimental analysis of
      behavior.
AB  - Greek-English and English-Greek translations of expressions in the experimental
      analysis of behavior are presented. Included is a short discussion of some of the
      problems which arose, partly because of the mentalistic nature of Greek science.

PMID- 16812133
TI  - The effects of the stimulus-reinforcer correlation in a discrete-trials IRT>t
      procedure.
AB  - The correlation between a keylight and food in a discrete-trials, interresponse
      time-greater-than 6-sec (IRT>6-sec) procedure was varied by manipulating the rate
      of response-independent food presentation in the intertrial interval. When the
      correlation was positive, the rates of pecking in the IRT>6-sec condition were
      high and food was obtained on only about 5% of the trials. Likewise, responding
      was maintained at a high rate in yoked birds that received the same presentations
      of the light and food as the birds in the IRT>6-sec condition. When the rate of
      reinforcement between trials was equated to or made greater than the rate of
      reinforcement within trials, the response rate decreased for all birds, and those
      decreases were considerably larger for the yoked birds. However, the percentage
      of trials in which reinforced responses occurred under the IRT>6-sec procedure
      did not increase substantially when the light and food were either uncorrelated
      or negatively correlated. The percentage of trials in which a reinforcer was
      obtained increased when the keylight was left on continuously and the
      discriminative stimulus was not presented on the key. The results show that the
      stimulus-reinforcer correlation affects responding in the discrete-trials IRT>6
      sec procedure, but that the effects of the stimulus-reinforcer correlation vary
      as a function of whether reinforcement is response-dependent or response
      independent. The differences between the effects of response-independent and
      response-dependent pairings and nonpairings of the light and food are best
      accounted for in terms of differences in the control of responding by background
      stimuli.

PMID- 16812134
TI  - Reinforcing the absence of fixed-ratio performance.
AB  - Pigeons received food for key pecking according to a fixed-ratio schedule, while,
      at the same time, food also was available for not pecking for a specified time.
      With a fixed ratio of 60, responding was not affected by not-pecking times of 80
      or 40 seconds, and was eliminated completely at 10 seconds. With ratios of 180,
      pecking stopped with not-pecking times of 80 seconds or less; with ratios of 300,
      it stopped at 120 seconds or less. Not-responding schedules produced steady-state
      performance immediately following contact with the schedule. With return to the
      fixed-ratio schedule alone, response rate sometimes was elevated temporarily.
      When response-independent food presentations replaced the not-pecking schedule,
      response rate often was enhanced, and the ratio pattern was lost. Only the
      highest densities of food delivery eliminated responding, even with a fixed ratio
      of 300. In general, the effects corresponded to those of punishment, except that
      contrast had appeared both during and after punishment, and now appeared only
      after the response elimination procedure was suspended.

PMID- 16812135
TI  - Temporal control of behavior and the power law.
AB  - The performance of rats and pigeons under fixed-interval schedules was studied in
      two experiments. The duration of postreinforcement pause was a declining
      proportion of fixed-interval duration. For pigeons this was true both when the
      duration of the reinforcer was fixed and when it was increased in direct
      proportion to increases in fixed-interval duration; the longer reinforcer
      durations did, however, lengthen the postreinforcement pause at higher schedule
      values. A quantitative analysis of data from Experiments 1 and 2 and from other
      studies showed that fractional exponent power functions described the
      relationship between postreinforcement pause and fixed-interval value; similar
      functions have previously been observed in studies of temporal differentiation.
      It was concluded that power functions reflect a direct causal, rather than
      artifactual, relationship between performance and the temporal requirements of
      reinforcement schedules.

PMID- 16812136
TI  - Periodicities within a fixed-interval session.
AB  - Within-session periodicities in number of responses per interval and
      postreinforcement pauses were investigated on fixed-interval schedules of 1, 2,
      and 3 minutes with rats. Postreinforcement pause values and the number of
      responses in successive intervals were not systematically related. The direction
      of change of these variables from one pair of intervals to the next revealed
      periodicities in that the direction of change varied more than would be expected
      by chance. A response prevention technique used to manipulate the length of time
      spent responding in an interval had little effect on the postreinforcement pause
      value of the next interval except when only a single response was permitted in an
      interval. This procedure tended to reduce the postreinforcement pause value of
      the next interval to an abnormally low level.

PMID- 16812137
TI  - Partial avoidance contingencies: Absolute omission and punishment probabilities.
AB  - Avoidance contingencies were defined by the absolute probability of the
      conjunction of responding or not responding with shock or no shock. The
      "omission" probability (rho(00)) is the probability of no response and no shock.
      The "punishment" probability (rho(11)) is the probability of both a response and
      a shock. The traditional avoidance contingency never omits shock on nonresponse
      trials (rho(00)=0) and never presents shock on response trials (rho(11)=0). Rats
      were trained on a discrete-trial paradigm with no intertrial interval. The first
      lever response changed an auditory stimulus for the remainder of the trial.
      Shocks were delivered only at the end of each trial cycle. After initial training
      under the traditional avoidance contingency, one group of rats experienced
      changes in omission probability (rho(00)>0), holding punishment probability at
      zero. The second group of rats were studied under different punishment
      probability values (rho(11)>0), holding omission probability at zero. Data from
      subjects in the omission group looked similar, showing graded decrements in
      responding with increasing probability of omission. These subjects approximately
      "matched" their nonresponse frequencies to the programmed probability of shock
      omission on nonresponse trials, producing a very low and approximately constant
      conditional probability of shock given no response. Subjects in the punishment
      group showed different sensitivity to increasing absolute punishment probability.
      Some subjects decreased responding to low values as punishment probability
      increased, while others continued to respond at substantial levels even when
      shock was inevitable on all trials (noncontingent shock schedule). These results
      confirm an asymmetry between two dimensions of partial avoidance contingencies.
      When the consequences of not responding included occasional omission of shock,
      all subjects showed graded sensitivity to changes in omission frequency. When the
      consequences of responding included occasional shock delivery, some subjects
      showed graded sensitivity to punishment frequency while others showed control by
      overall shock frequency as well.

PMID- 16812138
TI  - Bar press and bar release as avoidance responses.
AB  - Two experiments were performed in which rats had to avoid shock by both pressing
      and releasing a bar within specified intervals. When the release-shock interval
      was held constant and the press-shock interval was increased, response rate
      decreased and bar holding increased. When the press-shock interval was held
      constant and the release-shock interval was increased, both response rate and bar
      holding decreased.

PMID- 16812139
TI  - Autoshaping with common and distinctive stimulus elements, compact and dispersed
      arrays.
AB  - Four groups of pigeons were trained with a standard autoshaping procedure in
      which a brief fixed-duration interval always followed by a grain delivery
      alternated with a longer variable-duration interval never associated with grain
      delivery. One of two stimuli was always presented during each interval. One of
      them contained three black dots and a black star on a green background; the other
      contained four black dots on a green background. The four elements of each
      stimulus were arranged in a more compact array for two groups and in a more
      dispersed array for the other two groups. Which of the two stimuli preceded grain
      delivery was counterbalanced within each pair of groups. The speed of occurrence
      of the first autoshaped peck was not affected by whether the stimulus containing
      the distinctive star element preceded grain delivery, but autoshaping was faster
      when the stimulus arrays were compact than when they were dispersed. During 560
      response-independent training trials that followed the first autoshaped peck,
      this pattern reversed; both discriminative control over responding and the
      relative frequency of pecking the stimulus that preceded grain delivery were
      greater for the two groups where this stimulus contained the discriminative
      element than for the two groups where it contained only common elements. During
      subsequent testing with stimuli containing only a single element each, the
      distinctive feature was responded to proportionately more often by the two groups
      for which it had been an element of the stimulus preceding grain delivery than by
      the two groups for which it had been an element of the stimulus complex that
      never was associated with grain delivery. These data add further support to the
      hypothesis that the initial occurrence of autoshaped responding and its
      subsequent maintenance are not affected by the same variables. They also suggest
      that automaintenance is as sensitive as response-dependent training to the
      presence or absence of a distinctive stimulus element among several common
      elements and that this sensitivity appears to be independent of the specific
      method used for presenting the stimuli during automaintenance.

PMID- 16812140
TI  - Automaintenance without stimulus-change reinforcement: Temporal control of key
      pecks.
AB  - Yoked pairs of experimentally naive pigeons were exposed to a modified
      autoshaping procedure in which key pecking by the leader birds postponed both
      keylight termination and access to grain for the leader and the follower bird.
      Key pecking developed and was maintained in all birds and continued through two
      reversals of roles in the yoked procedure. Although temporal control developed
      more slowly in follower birds, asymptotic temporal distributions of key pecking
      were similar for all birds in both leader and follower roles; maximum responding
      occurred soon after keylight onset and decreased to a minimum prior to
      reinforcement. Response distributions for both leader and follower birds were
      described by Killeen's (1975) mathematical model of temporal control. Follower
      birds received response-independent reinforcement, and the development by these
      birds of temporal distributions which are minimal immediately prior to
      reinforcement is without precedent in Pavlovian appetitive conditioning. However,
      maintenance of key pecking by the leader birds, whose responses postponed both
      stimulus-change and food reinforcement, supports an interpretation of autoshaped
      and automaintained key pecking as responding elicited by signaled grain
      presentation.

PMID- 16812141
TI  - Decision rules and signal detectability in a reinforcement-density
      discrimination.
AB  - Two probabilistic schedules of reinforcement, one richer in reinforcement, the
      other leaner, were overlapping stimuli to be discriminated in a choice situation.
      One of two schedules was in effect for 12 seconds. Then, during a 6-second choice
      period, the first left-key peck was reinforced if the richer schedule had been in
      effect, and the first right-key peck was reinforced if the leaner schedule had
      been in effect. The two schedule stimuli may be viewed as two binomial
      distributions of the number of reinforcement opportunities. Each schedule yielded
      different frequencies of 16 substimuli. Each substimulus had a particular type of
      outcome pattern for the 12 seconds during which a schedule was in effect, and
      consisted of four consecutive light-cued 3-second T-cycles, each having 0 or 1
      reinforced center-key pecks. Substimuli therefore contained 0 to 4 reinforcers.
      On any 3-second cycle, the first center-key peck darkened that key and was
      reinforced with probability .75 or .25 in the richer or leaner schedules,
      respectively. In terms of the theory of signal detection, detectability neared
      the maximum possible d' for all four pigeons. Left-key peck probability increased
      when number of reinforcers in a substimulus increased, when these occurred closer
      to choice, or when pellets were larger for correct left-key pecks than for
      correct right-key pecks. Averaged over different temporal patterns of
      reinforcement in a substimulus, substimuli with the same number of reinforcers
      produced choice probabilities that matched relative expected payoff rather than
      maximized one alternative.

PMID- 16812142
TI  - Response requirements as constraints on output.
AB  - Two experiments studied how added response requirements affected fixed-interval
      schedule performance. Experiment 1 involved tandem fixed-interval fixed-ratio
      schedules, and Experiment 2 studied conjunctive fixed-interval fixed-ratio
      schedules. In both, pigeons' output, defined as overall response rate or as
      responses during the interval, first increased and then decreased as the ratio
      was raised. With small ratio requirements, the frequency of reinforcement in time
      either did not change or decreased slightly. With progressively larger ratios,
      reinforcement frequency decreased consistently. Alternative explanations were
      discussed. The first, a reinforcement theory account, was that response strength
      is an increasing monotonic function of both the response requirement and
      reinforcement frequency, and the bitonic output function represents interacting
      effects. Increases in the response requirement accompanied by small changes in
      reinforcement frequency enhance output, but further increases result in large
      enough decrements in reinforcement frequency so that output is lowered. The
      second explanation does not view reinforcement as a basic process but, instead,
      derives from concepts of economics and conservation. Organisms allocate their
      behavior among alternatives so as to maximize value, where value is a function of
      the responses that can occur in a given situation under the set of restrictions
      imposed by particular schedules. One form of this theory explicitly predicts that
      output is a bitonic function of ratio requirements in simple ratio schedules.
      However, it was not clear that this model could explain the present effects
      involving joint ratio and interval schedule restrictions.

PMID- 16812143
TI  - Choice and number of reinforcers.
AB  - Pigeons were exposed to the concurrent-chains procedure in two experiments
      designed to investigate the effects of unequal numbers of reinforcers on choice.
      In Experiment 1, the pigeons were indifferent between long and short durations of
      access to variable-interval schedules of equal reinforcement density, but
      preferred a short high-density terminal link over a longer, lower density
      terminal link, even though in both sets of comparisons there were many more
      reinforcers per cycle in the longer terminal link. In Experiment 2, the pigeons
      preferred five reinforcers, the first of which was available after 30 sec, over a
      single reinforcer available at 30 sec, but only when the local interval between
      successive reinforcers was short. The pigeons were indifferent when this local
      interval was sufficiently long. The pigeons' behavior appeared to be under the
      control of local terminal-link variables, such as the intervals to the first
      reinforcer and between successive reinforcers, and was not well described in
      terms of transformed delays of reinforcement or reductions in average delay to
      reinforcement.

PMID- 16812144
TI  - The effect of signaled reinforcement availability on concurrent performances in
      humans.
AB  - During Phase I, three female human subjects pressed a button for monetary
      reinforcement in two-component concurrent variable-interval schedules. Five
      different reinforcement frequencies were used in component A, whereas the
      reinforcement frequency in component B was held constant. Absolute rates of
      responding conformed to equations proposed by Herrnstein to describe concurent
      performances, and the ratios of the response rates and the times spent in the two
      components conformed to the matching law. During Phase II, the availability of
      reinforcement in component A was signaled by the illumination of a lamp. This
      resulted in suppression of response rates in component A and elevation of
      response rates in component B, these changes being reflected in a distortion of
      the matching relationship which took the form of a bias in favor of component B.

PMID- 16812145
TI  - Choice: Effects of changeover schedules on concurrent performance.
AB  - The components of concurrent schedules were separated temporally by placing
      interval schedules on the changeover key. The rates of responding on both the
      main and changeover keys were examined as a function of the reinforcement rates.
      In the first experiment, the sensitivity of main-key performance to changing
      reinforcement rates was inversely related to the temporal separation of
      components, and changeover performance was monotonically related to the ratio of
      the reinforcement rates. In the second experiment, when the ratio of the
      reinforcement rates was scheduled to remain constant while the frequency of
      reinforcement was varied, changeover performance did not remain constant. A
      "sampling" interpretation of changeover responding was proposed and subsequently
      tested in a third experiment where extinction was always scheduled in one
      component and the frequency of reinforcement was varied in the second component.
      It was concluded that changeover performance can be interpreted using molar
      measures of reinforcement and that animals sample activities available to them at
      rates which are controlled by relative reinforcement rates.

PMID- 16812146
TI  - Effects of response-independent negative reinforcers on negatively reinforced key
      pecking.
AB  - Previous research has shown that presenting response-independent positive
      reinforcers reduces the response rate of an operant maintained by positive
      reinforcement. The present experiment investigated a similar effect using shock
      free time as a negative reinforcer. Brief shocks were delivered in the presence
      of a distinctive stimulus, and pigeon's key pecks were reinforced by the
      occasional presentation of a 2-minute shock-free period. Extra 2-minute shock
      free periods were added independently of behavior. For each of three pigeons,
      response rate during shock-on periods declined with added shock-free periods; the
      more frequently the extra shock-free periods occurred the greater the decline in
      response rate. This outcome is predicted by extending the Law of Effect to
      include negative reinforcement.

PMID- 16812147
TI  - Stimulus generalization along a dimension based on a verbal concept.
AB  - The present study examined generalization along a dimension based on a verbal
      concept of occupational status. The status dimension was scaled by students who
      placed occupation names into five status categories, Category 1 representing
      highest status and Category 5 the lowest status. In two experiments, key presses
      by students were occasionally reinforced when a slide showing an occupation name
      from Status Category 3 was present. For half the subjects, key presses were not
      reinforced during a name from Category 1; for the other half, presses were not
      reinforced during a name from Category 5. Occupation names from all status
      categories were later singly presented. In this generalization test, subjects
      typically divided the dimension into two parts, responding alike to all names
      within each part. The results suggest that generalization along a dimension in
      humans is mediated by a subject's verbal classifications of stimuli.

PMID- 16812148
TI  - Free-operant choice behavior: A molecular analysis.
AB  - Pigeons' pecks to two concurrent initial-link stimuli occasionally produced one
      of two mutually exclusive terminal links. Further responding to the terminal-link
      stimulus produced food under fixed-interval or fixed-ratio schedules. In such
      concurrent chained schedules, investigators rarely use a changeover delay to
      control superstitious switching, although it is customary to use a changeover
      delay in simple concurrent schedules in which choice responses produce food
      directly. When terminal-link fixed-interval schedules were equal or similar in
      duration and no changeover delay was employed, conditional probabilities of
      choice for a schedule were found to be lower if the last choice was for that
      schedule than if the last choice was for the other schedule ("switching
      dependency"). Imposition of a changeover delay with equal or unequal terminal
      links produced the opposite pattern: conditional probabilities of choice for a
      schedule were higher if the last choice was for that schedule than if the last
      choice was for the other schedule. Turning off all chamber lights during the
      changeover delay interval attenuated these "repetition dependencies." The results
      indicate that excessive switching can complicate the interpretation of data from
      concurrent chains much as from simple concurrent schedules, and that using
      blackouts to control switching may be preferable to using a changeover delay.

PMID- 16812149
TI  - Concurrent schedule assessment of food preference in cows.
AB  - Six dairy cows (Bos taurus) were trained on several pairs of concurrent variable
      interval schedules with different types of food available on each alternative.
      The required response was a plate press made by the animal's muzzle. Performance
      generally replicated that found with other species. The generalized matching law
      accounted for the preference data, showing that food preference could be
      quantitatively analyzed as a special case of response bias. The preference
      functions showed that the response- and time-allocation ratios were not as
      extreme as obtained reinforcement rate ratios (undermatching).

PMID- 16812150
TI  - Reinforcement magnitude and the inhibiting effect of reinforcement.
AB  - In a two-key concurrent variable-interval schedule (using pigeons), if the
      reinforcement frequency for one response is held constant while that for the
      other is increased, the rate of response on the constant key decreases. The
      immediate reinforcement for key pecking can usually be conceptualized as the
      change from a condition in which the key light is on and the food hopper light is
      off to one in which the key light is off and the hopper light is on. The
      prechange condition is associated with a delay to food of one-half the average
      interreinforcement interval in effect during this condition. The postchange
      condition is associated with a delay to food of about .5 seconds. The programming
      of additional reinforcement results in a decrease in the delay to food associated
      with the prechange stimulus condition, and thus a decrease in the value of the
      improvement that results from the change. This would appear to be analogous to a
      decrease in the amount of reinforcement, and thus sufficient explanation for the
      decrease in the rate of the response.

PMID- 16812151
TI  - Stimulus properties of conspecific behavior.
AB  - Two experiments identified the conditions in which the behavior of one bird
      acquired discriminative control of the behavior of a second bird. The schedule
      controlled behaviors of the "stimulus" bird were differentially correlated with
      the components of a multiple schedule according to which the pecking of an
      "experimental" bird produced food. In Experiment 1, three pairs of pigeons
      acquired a successive discrimination and two reversals with the conspecific
      stimuli. Experiment 2 included a control condition in which no systematic
      relationship existed between the conspecific stimuli and the component schedules.
      While differential responding during the components of the multiple schedule was
      again found when the conspecific stimuli were available, differential responding
      did not occur in the control condition. Test conditions included in the
      experiments indicated that (a) the differential responding was not dependent on
      the discriminative properties of reinforcement, (b) the pecking of the stimulus
      and experimental birds was temporally interrelated, (c) the visual conspecific
      stimuli were critical to the maintenance of the discrimination, and (d) the
      observed stimulus control immediately generalized to an unfamiliar conspecific.

PMID- 16812152
TI  - Grooming movements as operants in the rat.
AB  - Two experiments investigated the effect of contingent food deliveries on grooming
      movements in rats. The grooming sequence was divided into three topographically
      distinct behaviors: paw washing, face washing, and body washing. The first
      experiment found that rates of paw washing and body washing increased reliably
      under a food contingency, but face washing did not. A second experiment
      replicated these findings, and, in addition, showed that the average duration of
      paw washing and body washing decreased in length when followed by food. Placing a
      contingency on face washing, however, produced an increase in the rate of paw
      washing but no increase in face washing. It was concluded that, on the one hand,
      paw washing and body washing may be influenced by operant contingencies in the
      same way as behaviors such as lever pressing. On the other hand, increases in paw
      washing under the face washing contingency suggested that increases in the rate
      of grooming movements may occur by means other than operant relations.

PMID- 16812153
TI  - Operant and nonoperant vocal responding in the mynah: Complex schedule control
      and deprivation-induced responding.
AB  - Several recent studies have been concerned with operant responses that are also
      affected by nonoperant factors, (e.g., biological constraints, innate behavior
      patterns, respondent processes). The major reason for studying mynah vocal
      responding concerned the special relation of avian vocalizations to nonoperant
      emotional and reflexive systems. The research strategy was to evaluate operant
      and nonoperant control by comparing the schedule control obtained with the vocal
      response to that characteristic of the motor responses of other animals. We
      selected single, multiple, and chain schedules that ordinarily produce disparate
      response rates at predictable times. In multiple schedules with one component
      where vocal responding ("Awk") was reinforced with food (fixed-ratio or fixed
      interval schedule) and one where the absence of vocal responding was reinforced
      (differential reinforcement of other behavior), response rates never exceeded 15
      responses per minute, but clear schedule differences developed in response rate
      and pause time. Nonoperant vocal responding was evident when responding endured
      across 50 extinction sessions at 25% to 40% of the rate during reinforcement. The
      "enduring extinction responding" was largely deprivation induced, because the
      operant-level of naive mynahs under food deprivation was comparable in magnitude,
      but without deprivation the operant level was much lower. Food deprivation can
      induce vocal responding, but the relatively precise schedule control indicated
      that operant contingencies predominate when they are introduced.

PMID- 16812154
TI  - Percentage reinforcement and choice.
AB  - Pigeons responded on identical concurrent variable-interval schedules (choice
      phase), producing outcomes of either periodic reinforcement schedules always
      terminating in reinforcement (reliable schedule) or otherwise identical schedules
      providing reinforcement on only a percentage of instances (percentage
      reinforcement schedule). Comparisons of this type constituted two assessments of
      the generality of preference for percentage reinforcement reported by Kendall
      (1974). In a third set of conditions, a reliable schedule was pitted against a
      percentage reinforcement schedule in which the more negative outcome was a leaner
      schedule of reinforcement (rather than nonreinforcement, as in the other two
      conditions). In all three types of conditions, the schedule providing the higher
      rate of reinforcement was preferred. Results from a subsequent manipulation
      suggest that Kendall's contrasting results may have depended on the fact that the
      stimuli in his choice phase (unlit keys) were physically identical to the
      stimulus correlated with the nonchosen outcome in his outcome phase.

PMID- 16812155
TI  - Constituents of response rates.
AB  - Response rate and the proportion of time pigeons allocated to a key-pecking
      activity were measured on several basic types of reinforcement schedules.
      Reinforcement frequency was varied within each type of basic schedule, and the
      effects on two constituents of response rate were noted. Propensity, the
      proportion of time the birds spent on a platform in front of the key, showed very
      consistent effects as reinforcement frequency varied: in general, it decreased
      when reinforcement frequency markedly decreased and it increased when
      reinforcement frequency increased. Speed, key pecks per unit of time spent on the
      platform, showed inconsistent effects when reinforcement frequency varied.
      Consequently, response rate showed less consistent effects than did propensity.
      Cumulative response records demonstrated the existence of several different types
      of transitions or boundary states between the key-pecking activity and other
      activities. The types of transitions that occurred between activities depended on
      both the type of reinforcement schedule and the frequency of reinforcement. The
      propensity data support the position that general laws of behavior can be based
      on temporal measures of behavior. The speed data suggest that, if a complete
      assessment of the dynamic properties of behavior is to be achieved, measures of
      behavior must incorporate the structural variations in the operant unit.

PMID- 16812156
TI  - Chained schedules of avoidance: Reinforcement within and by avoidance situations.
AB  - Four rats were exposed to chained schedules with variable-cycle avoidance in both
      links. Responding in the initial link cancelled shocks scheduled once per minute
      and, according to a conjoint fixed-ratio schedule, produced a terminal link where
      scheduled shock rates varied from 0 to 8 shocks per minute in different
      conditions of the experiment. Response rates in the terminal link increased as a
      function of the scheduled shock rate. Response rates in the initial link, on the
      other hand, decreased as a function of the shock rate actually received (rather
      than scheduled) in the terminal link. While consistent with other studies of
      aversive control, these results differ from those obtained in chained schedules
      of positive reinforcement in that increases in reinforcement within the terminal
      link of the chain did not systematically increase the reinforcing value of that
      link.

PMID- 16812157
TI  - Defining behavioral contrast for multiple schedules.
AB  - Two different definitions of behavioral contrast have been used for multiple
      schedules. One, interschedule, definition identifies contrast as changes in the
      rates of responding which occur when subjects move from one multiple schedule to
      another. The other, intraschedule, definition emphasizes changes in the rates of
      responding which occur relative to a baseline rate of responding. The baseline is
      the rate of responding emitted during a multiple schedule that supplies equal
      rates of reinforcement in the two components. The distinction between these two
      definitions is important for empirical and theoretical reasons. For example,
      theoretical confusion has arisen when the interschedule definition has been used
      to test and reject theories which implicitly define contrast by the intraschedule
      definition.

PMID- 16812158
TI  - Toward a quantitative theory of punishment.
AB  - In two experiments, pigeons' key pecking for food on concurrent variable-interval
      schedules was punished with electric shock according to concurrent variable
      interval punishment schedules. With unequal frequencies of food but equal rates
      of punishment associated with the two keys and at several intensities of shock,
      the response and time allocation of all six pigeons overmatched the obtained
      relative frequency of food. The overmatching was predicted by a subtractive model
      of the interaction between punishment and positive reinforcement but not by two
      alternative models. Increases in the k and r(e) parameters of the generalized
      matching law could not account for the observed shifts in preference.

PMID- 16812159
TI  - Choice and reinforcement delay.
AB  - Previous studies of choice between two delayed reinforcers have indicated that
      the relative immediacy of the reinforcer is a major determinant of the relative
      frequency of responding. Parallel studies of choice between two interresponse
      times have found exceptions to this generality. The present study looked at the
      choice by pigeons between two delays, one of which was always four times longer
      than the other, but whose absolute durations were varied across conditions. The
      results indicated that choice is not uniquely determined by the relative
      immediacy of reinforcement, but that absolute delays are also involved. Models
      for concurrent chained schedules appear to be more applicable to the present data
      than the matching relation; however, these too failed to predict choice for long
      delays.

PMID- 16812160
TI  - Uncertainty reduction, conditioned reinforcement, and observing.
AB  - In a concurrent-chains procedure, pigeons chose between equivalent mixed and
      multiple fixed-interval schedules of reinforcement. In the first experiment,
      preference for the multiple schedule was higher when the probability of the
      shorter fixed interval was less than .50 than for complementary points, an
      outcome consistent with the delay-reduction hypothesis of conditioned
      reinforcement and observing, but inconsistent with the uncertainty-reduction
      hypothesis which requires symmetrical preferences with a maximum when the two
      intervals are equiprobable. A second experiment assessed preference for
      equivalent mixed and multiple schedules when each choice outcome resulted in two
      reinforcements, one on the longer and one on the shorter fixed interval. The
      order of the two fixed intervals was determined probabilistically. Pigeons again
      preferred multiple to mixed schedules, although multiple-schedule preference did
      not vary systematically with the likelihood of the shorter fixed interval
      occurring first. The results from these choice procedures are consistent with
      those from the observing-response literature in suggesting that the strength of a
      stimulus cannot be well described as a function of the degree of uncertainty
      reduction the stimulus provides about reinforcement.

PMID- 16812161
TI  - Positive conditioned suppression: Transfer of performance between contingent and
      noncontingent reinforcement situations.
AB  - Five homing pigeons were trained on concurrent variable-interval schedules. A
      fixed-duration stimulus was occasionally presented on one key; and, in various
      conditions, this stimulus terminated (a) without reinforcement, (b) in
      noncontingent reinforcement, (c) with reinforcement contingent on a response on
      the key on which the stimulus was presented, and (d) with reinforcement
      contingent on a response on the key on which the stimulus was not presented.
      Initially, a stimulus terminating in noncontingent reinforcement generally
      produced decreased response rates on both keys during the stimulus.
      Contingencies, however, reliably produced increased rates during the stimulus on
      the key on which the contingency was arranged, relative to the rate on the
      concurrently available key. Contingency conditions were followed by
      noncontingency conditions in which the separation of rates caused by
      contingencies was maintained. When rates during the stimulus were compared with
      response rates on the same keys in the absence of the stimulus, contingency
      caused rate increases and decreases were again found, but only the rate decreases
      were maintained in subsequent noncontingency conditions. Further data suggested
      that the contingency-caused rate changes were not maintained when the stimulus
      terminated without reinforcement, and that they were unaffected by a threefold
      decrease in the reinforcement rate provided by the baseline schedules. The
      results support the suggestion that performance in the positive conditioned
      suppression procedure results from concurrent and multiple schedule interactions.
      They further suggest that the production of either acceleration or suppression is
      dependent on adventitious and historical contingencies.

PMID- 16812163
TI  - Editorial.

PMID- 16812162
TI  - Choice of timeout during response-independent food schedules.
AB  - Rats' lever pressing terminated visual or auditory stimuli associated with fixed
      time or variable-time schedules of food delivery and produced a timeout period
      during which food delivery could not occur. Lever pressing during a timeout
      period reinstated the food-associated stimuli and again permitted food delivery
      according to the fixed-time or variable-time schedules. The mean interfood
      interval ranged from 1 minute to 16 minutes (variable-time schedules) or 32
      minutes (fixed-time schedules); the timer controlling schedule intervals did not
      stop during timeout periods. The percentage of session time spent in timeout
      increased when the mean interfood intervals were lengthened and decreased when
      the mean interfood intervals were shortened. Timeouts were initiated most
      frequently about half way between successive food deliveries (fixed-time
      schedules) or after 15 seconds or more had lapsed since the last food delivery
      (variable-time schedules). Elimination of food delivery increased the percentage
      of session time spent in timeout, and elimination of the timeout contingency
      decreased lever press rates. When timeout was produced only when the lever was
      held in the depressed position, little time was spent in timeout. The main
      determinants of timeout initiation and termination appeared to be the rate of
      food delivery, freedom of movement during timeout, and the stimulus change
      associated with initiation and termination of timeout.

PMID- 16812164
TI  - Development of complex, stereotyped behavior in pigeons.
AB  - A pigeon's peck on one key moved a light down one position in a 5x5 matrix of
      lights, while a peck on another key moved the light across one position.
      Reinforcement depended upon the occurrence of four pecks on each key (moving the
      matrix light from the top left to the bottom right), and a fifth peck on either
      key ended a trial without food. Though there were 70 different sequences that led
      to reinforcement, each of 12 pigeons developed a particular, stereotyped sequence
      which dominated its behavior (Experiment 1). Extinction produced substantial
      increases in sequence variability (Experiment 2). Removal of the matrix cues
      disrupted performance, though it partially recovered with extended training
      (Experiment 3). The pigeons did not master a contingency which required a
      different sequence on the current trial than on the previous one (Experiment 4),
      though they were able to learn to emit sequences which began with either left
      left or left-right response patterns (Experiment 5). The experiments suggest that
      contingencies of reinforcement may contribute to the creation of complex units of
      behavior, and that stereotypy may be a likely consequence of contingent
      reinforcement.

PMID- 16812165
TI  - Contingency and stimulus change in chained schedules of reinforcement.
AB  - Higher rates of pecking were maintained by pigeons in the middle component of
      three-component chained fixed-interval schedules than in that component of
      corresponding multiple schedules (two extinction components followed by a fixed
      interval component). This rate difference did not occur in equivalent tandem and
      mixed schedules, in which a single stimulus was correlated with the three
      components. The higher rates in components of chained schedules demonstrate a
      reinforcing effect of the stimulus correlated with the next component; the
      acquired functions of this stimulus make the vocabulary of conditioned
      reinforcement appropriate. Problems in defining conditioned reinforcement arise
      not from difficulties in demonstrating reinforcing effects but from disagreements
      about which experimental operations allow such reinforcing effects to be called
      conditioned.

PMID- 16812166
TI  - Response strength in multiple periodic and aperiodic schedules.
AB  - Responding in multiple periodic and aperiodic schedules of equal mean
      reinforcement rate was examined during extinction, satiation, and in the presence
      of various free-food schedules. In Experiments I and II, pigeons were trained on
      multiple variable-interval-fixed-interval schedules. Decreases in the rate of
      responding due to extinction, satiation, or food schedules were approximately
      equal regardless of the temporal pattern of reinforcer presentation. In
      Experiment III, pigeons responded on a two-component multiple schedule in which
      each component was a two-member homogeneous response chain terminating in a fixed
      interval schedule during one component and in a variable-interval schedule during
      the other. The length of both terminal links was varied over a series of
      conditions. Initial-link responding in the fixed-interval component was reduced
      more by increasing terminal-link length than was initial-link responding in the
      variable-interval component. However, no differences in resistance to satiation
      and extinction were obtained across the fixed and variable components. If the
      relative decrease in responding produced by satiation and extinction is used as
      an index of the "value" of the conditions maintaining responding, then these data
      suggest that fixed and variable schedules of equal mean length are equally
      valued. This conclusion, however, is not consistent with findings of preference
      for variable over fixed schedules obtained in studies using concurrent-chain
      procedures.

PMID- 16812167
TI  - Alternative fixed-ratio fixed-interval schedules of reinforcement.
AB  - Five rats were trained under alternative fixed-ratio fixed-interval schedules, in
      which food reinforcement was provided for the completion of either a fixed-ratio
      or a fixed-interval requirement, whichever was met first. Overall response rate
      and running rate (the rate of responding after the postreinforcement pause)
      decreased for all subjects as the fixed-ratio value increased. As the proportion
      of reinforcements obtained from the fixed-ratio component increased and the
      alternative schedule approached a simple fixed ratio, overall response rate and
      running rate both increased; conversely, as the proportion of reinforcements
      obtained from the fixed-interval component increased and the alternative schedule
      approached a simple fixed interval, response rates decreased. Postreinforcement
      pause length increased linearly as the average time between reinforcements
      increased, regardless of the schedule parameters. A break-run pattern of
      responding was predominant at low- and medium-valued fixed ratios. All subjects
      displayed at least occasional positively accelerated responding within
      interreinforcement intervals at higher fixed-ratio values.

PMID- 16812168
TI  - Reduction of shock duration as negative reinforcement in free-operant avoidance.
AB  - Rats were trained on a free-operant procedure in which shock duration was
      controlled by responses within a limited range of interresponse times. Shocks of
      1.6-mA intensity occurred randomly with average density of 10 shocks per minute.
      As long as interresponse times were 15 seconds or less, any shocks received were
      at the briefer of two durations (.3 second). Whenever interresponse times
      exceeded 15 seconds, any shocks received were at the longer duration (1.0
      second). For six of eight animals, avoidance responding developed quickly and
      reached levels of better than 90%. Four yoked animals stopped responding within
      the first few sessions. Shock duration reduction without change in shock
      probability or intensity was sufficient for the acquisition and maintenance of
      avoidance responding.

PMID- 16812169
TI  - Reinforcement and punishment effects in concurrent schedules: A test of two
      models.
AB  - The joint effects of punishment and reinforcement on the pigeon's key-peck
      response were examined in three choice experiments conducted to compare
      predictions of Farley and Fantino's (1978) subtractive model with those made by
      Deluty's (1976) and Deluty and Church's (1978) model of punishment. In Experiment
      1, the addition of equal punishment schedules to both alternatives of a
      concurrent reinforcement schedule enhanced the preference exhibited for the more
      frequent reinforcement alternative. Experiment 2 demonstrated decreases in the
      absolute response rate for each member of a concurrent reinforcement schedule
      when increasing frequencies of punishment were added to each alternative.
      Experiment 3 found that preference for the denser of two reinforcement schedules
      diminished when the absolute frequencies of reinforcement were increased by a
      constant factor and conditions of punishment for both alternatives were held
      constant. Diminished preferences were obtained regardless of whether the
      frequency of punishment associated with the denser reinforcement schedule was
      greater or less than that associated with the lean reinforcement alternative. The
      results from all three experiments uniquely supported Farley and Fantino's (1978)
      subtractive model of punishment and reinforcement.

PMID- 16812170
TI  - Short-term memory in the rhesus monkey: A behavioral analysis of delayed-response
      performance.
AB  - This study obtained quantitative data on the bodily orientations of rhesus
      monkeys in a delayed-response task and determined whether such orientations
      mediate the correct response in a choice trial. The basic task was a two-key
      chain schedule with the key leading to food signaled in the initial component.
      During the subsequent delay interval, the signal was removed, but it was
      necessary that one of the keys be pressed to advance the schedule to the terminal
      choice component. The position of the key pressed thus indicated orientation
      during the delay interval. When the monkeys had free access to the left and right
      keys, they tended to press the key leading to food throughout the chain schedule
      components and received food on more than 85% of the trials, even when the delay
      was extended to 20 seconds. However, when orientation toward the food key was
      disrupted by forcing the monkeys to press an extraneous center key during the
      delay, choice performance deteriorated. Requiring the center key presses early,
      rather than late, in the delay component had a strong disruptive effect. The
      relation of the results to the mediating coding-response hypothesis is discussed.

PMID- 16812171
TI  - Long-term potential for imprinting in ducks and chickens.
AB  - In the first of five experiments, three of four adult ducks who had been reared
      in visual isolation gradually developed strong approach responses towards a
      moving panel of colored lights. Experiment 2 provided evidence that the ducks'
      approach response reflected the same sort of social attachment that is typically
      formed to moving objects by newly hatched ducklings. Experiment 3 revealed that
      the fourth duck would not approach the moving stimulus even after additional
      exposure to it, but would approach a conspecific after group housing had been
      enforced for seven days. In Experiment 4, none of five adult chickens who had
      been reared in visual isolation developed approach responses towards the moving
      stimulus, even though in Experiment 5, newly hatched chicks approached the
      stimulus quite readily. Taken together, these findings (a) indicate that ducks
      retain the ability to form filial-type attachments to novel objects throughout
      their lives, and (b) offer preliminary evidence that chickens do not retain this
      ability into adulthood.

PMID- 16812172
TI  - An analytic comparison of Herrnstein's equations and a multivariate rate
      equation.
AB  - Herrnstein's equations are approximations of the multivariate rate equation at
      ordinary rates of reinforcement and responding. The rate equation is the result
      of a linear system analysis of variable-interval performance. Rate equation
      matching is more comprehensive than ordinary matching because it predicts and
      specifies the nature of concurrent bias, and predicts a tendency toward
      undermatching, which is sometimes observed in concurrent situations. The rate
      equation contradicts one feature of Herrnstein's hyperbola, viz., the
      theoretically required constancy of k. According to the rate equation,
      Herrnstein's k should vary directly with parameters of reinforcement such as
      amount or immediacy. Because of this prediction, the rate equation asserts that
      the conceptual framework of matching does not apply to single alternative
      responding. The issue of the constancy of k provides empirical grounds for
      distinguishing between Herrnstein's account and a linear system analysis of
      single alternative variable-interval responding.

PMID- 16812173
TI  - A revised list of Spanish translations of operant terminology.
AB  - The experimental analysis of behavior has grown enormously in Latin America
      within the last decade. This paper offers an updating revision of suggested
      Spanish translations of operant expressions.

PMID- 16812174
TI  - The role of contingencies and "principles of behavioral variation" in pigeons'
      pecking.
AB  - Staddon and Simmelhag's proposal that behavior is produced by "principles of
      behavioral variation" instead of contingencies of reinforcement was tested in two
      experiments. In the first experiment pigeons were exposed to either a fixed
      interval schedule of response-contingent reinforcement, an autoshaping schedule
      of stimulus-contingent reinforcement, or a fixed-time schedule of noncontingent
      reinforcement. Pigeons exposed to contingent reinforcement came to peck more
      rapidly than those exposed to noncontingent reinforcement. Staddon and
      Simmelhag's "principles of behavioral variation" included the proposal that
      patterns (interim and terminal) were a function of momentary probability of
      reinforcement. In the second experiment pigeons were exposed to either a fixed
      time or a random-time schedule of noncontingent reinforcement. Pecking showed a
      constant frequency of occurrence over postfood time on the random-time schedule.
      Most behavior showed patterns on the fixed-time schedule that differed in overall
      shape (i.e., interim versus terminal) from those shown on the random-time
      schedule. It was concluded that both the momentary probability of reinforcement
      and postfood time can affect patterning.

PMID- 16812175
TI  - Physical restraint produces rapid acquisition of the pigeon's key peck.
AB  - The acquisition and maintenance of autoshaped key pecking in pigeons was studied
      as a function of intertrial interval. At each of six intervals, which ranged from
      12 seconds to 384 seconds, four pigeons were physically restrained during
      training while four other pigeons were not restrained. Restrained subjects
      acquired key pecking faster and with less intragroup variability at each
      interval. The effects of restraint were specific to acquisition and were not
      evident in maintained responding after five postacquisition sessions.

PMID- 16812176
TI  - Recording and storing data for yoked-control comparisons.

PMID- 16812177
TI  - Psychophysics of key-peck duration in the pigeon.
AB  - The duration of the pigeon's key peck was differentially reinforced in either a
      trials or a free-operant procedure. Mean emitted peck duration was a power
      function of the duration required for food delivery to occur. The exponents of
      the power function differed considerably from those observed in earlier research
      involving longer duration responses in pigeons and other species. The
      coefficients of variation also did not correspond with those of the earlier
      research on other responses, nor did consideration of the durations actually
      reinforced resolve the differences. Duration was neither a function of response
      rate nor of intermittency of reinforcement. Key-peck duration was changed in an
      orderly way by differential reinforcement. However, it appeared to be more
      strongly determined by its duration in the absence of differential reinforcement
      than were longer duration responses.

PMID- 16812178
TI  - Reinforcement for errors in a signal-detection procedure.
AB  - Six pigeons were trained on a signal-detection procedure. They were required to
      peck the left key when a 5-second white light had been presented, and the right
      key when a 10-second light had been presented. These two correct responses were
      followed by food reinforcement with a probability of .7. Errors, left responses
      after the 10-second stimulus or right responses after the 5-second stimulus, were
      initially followed by a 3-second blackout of the chamber. In nine subsequent
      experimental conditions, errors were followed by food reinforcement with
      increasing probability while the probability of reinforcement for correct
      responses was kept constant. The percentage of correct responses decreased as
      error reinforcement probability increased. A matching model of detection
      performance, in which discrimination is a joint function of stimulus
      discriminability and stimulus-reinforcement association, provided a convincing
      fit to the data and to two sets of published data. The model also fitted
      published data on multiple and multiple-concurrent free-operant performance. This
      description of detection performance in terms of matching offers both accurate
      prediction of complex behavior and measures of discriminability with wide
      generality.

PMID- 16812179
TI  - Memory for sequences of stimuli and responses.
AB  - Two experiments sought to determine if pigeons could discriminate and remember
      recent sequences of stimuli and responses. A variant of Konorski's short-term
      memory procedure involving successive presentation of sample and test stimuli was
      used. The samples were stimulus-response pairs of the form, (S-R)(1)-(S-R)(2).
      Differential test responding disclosed memory of the two-item samples, with birds
      showing earlier and greater control by the second item than the first (Experiment
      1). When the retention interval separating the second item of the sample sequence
      from the test stimulus was lenghtened from .5 to 2.0 or 4.0 sec, a systematic
      loss of stimulus control resulted; however, when varied over the same temporal
      range, the interval between the two items of the sample sequence had a much
      smaller effect, or none at all (Experiment 2). These results support an account
      of response-sequence differentiation that stresses short-term memory of organized
      behavior patterns.

PMID- 16812180
TI  - A comparison of ratio and interval reinforcement schedules with comparable
      interreinforcement times.
AB  - Pigeons were trained to peck keys on fixed-ratio and fixed-interval schedules of
      food reinforcement. Both schedules produced a pattern of behavior characterized
      as pause and run, but the relation of pausing to time between reinforcers
      differed for the two schedules even when mean time between reinforcers was the
      same. Pausing in the fixed ratio occupied less of the time between reinforcers
      for shorter interreinforcer times. For two of three birds, the relation was
      reversed at longer interreinforcer times. As an interreinforcer time elapsed,
      there was an increasing tendency to return to responding for the fixed interval,
      but a roughly constant tendency to return to responding for the fixed-ratio
      schedule. In Experiment 1 these observations were made for both single
      reinforcement schedules and multiple schedules of fixed-ratio and fixed-interval
      reinforcement. In Experiment 2 the observations were extended to a comparison of
      fixed-ratio versus variable-interval reinforcement schedules, where the
      distribution of interreinforcement times in the variable interval approximated
      that for the fixed ratio.

PMID- 16812181
TI  - Preference for free choice over forced choice in pigeons.
AB  - In a six-key chamber variable-interval initial links of concurrent-chain
      schedules operated on two lower white keys. Terminal links operated on four upper
      keys; green keys were correlated with fixed-interval reinforcement and red keys
      with extinction. Free-choice terminal links arranged three green keys and one red
      key; forced-choice terminal links arranged one green key and three red keys.
      Thus, terminal links were equivalent in number, variety, and information value
      (in bits) of the keylights. Preferences (relative initial-link rates) were
      studied both with location of the odd key color varying over successive terminal
      links and with the odd color fixed at key locations that had controlled either
      relatively high or relatively low terminal-link response rates. Free choice was
      consistently preferred to forced choice. Magnitude of preference did not vary
      systematically with terminal-link response rate or stimulus control by green and
      red keys. The origins of free-choice preference could be ontogenic or phylogenic:
      organisms may learn that momentarily preferred alternatives are more often
      available in free than in forced choice, and evolutionary contingencies may favor
      the survival of organisms that prefer free to forced choice.

PMID- 16812183
TI  - Editorial.

PMID- 16812182
TI  - The contribution of an added counter to a fixed-ratio schedule.
AB  - Although previous research showed that a visual counter increased the rate of
      responding on a large fixed-ratio schedule, a theoretical analysis of the factors
      responsible for fixed-ratio performance suggests that the primary control by
      number of responses since reinforcement is to weaken the performance. The present
      experiment employed a multiple schedule in which the same fixed-ratio value
      alternated with and without an added counter. It tested the hypothesis that the
      differential reinforcement of high-rate responding masked the attenuation of the
      fixed-ratio performance from the unoptimal discriminative control produced by the
      fixed relation between number of responses and reinforcement. In the present
      experiment the postreinforcement pause was consistently longer in the components
      with the added counter, while running rates remained comparable between the
      components of the multiple schedule. Both components of the multiple schedule
      involved differential reinforcement of high-rate responding while only the
      components with the added counter amplified the discriminative control by number
      of pecks since reinforcement.

PMID- 16812184
TI  - Choice between rewards differing in amount and delay: Toward a choice model of
      self control.
AB  - A concurrent-chain procedure was used to study pigeons' choices between rewards
      differing in both amount and delay. The shorter delay terminated with a 2-second
      access to grain whereas the longer delay terminated with a 6-second access to
      grain. The ratio of the delays was constant within a given condition while their
      absolute values were varied. Over conditions, ratios of 6:1, 3:1, and 3:2 were
      studied. As the absolute values of the delays to reinforcement increased,
      preference for the longer-delayed but larger reward decreased under both the 6:1
      and 3:1 ratios, but increased under the 3:2 ratio. These results are inconsistent
      with choice models predicting no change in preference when the ratios of delays
      and amounts are held constant. In addition, the change in preference under the
      3:1 ratio is inconsistent with a simple multiplicative interaction of the trade
      off between reinforcer amount and delay, and suggests that delay is a more potent
      determinant of choice than is amount. These results have implications for models
      that view choice between small immediate rewards and large but delayed rewards as
      underlying the behavior commonly called self control.

PMID- 16812185
TI  - Key-peck durations under behavioral contrast and differential reinforcement.
AB  - Pigeons were maintained on a multiple schedule in which both components were
      variable-interval one-minute schedules. When they were switched to a condition in
      which one component was extinction, behavioral contrast was observed. The median
      durations of the key pecks in the unchanged component did not decrease in size.
      The results are incompatible with a theory of behavioral contrast which considers
      the added pecks to be short-duration responses. In a second experiment, pigeons
      were required to emit short-duration key pecks in one component of a multiple
      schedule, and long-duration pecks in the other. Two of three pigeons learned to
      emit responses appropriate to the requirements of the component in effect,
      suggesting that the duration of the key-peck response is sensitive to
      differential reinforcement.

PMID- 16812186
TI  - A note on fitting Herrnstein's equation.

PMID- 16812187
TI  - Feedback functions for variable-interval reinforcement.
AB  - On a given variable-interval schedule, the average obtained rate of reinforcement
      depends on the average rate of responding. An expression for this feedback effect
      is derived from the assumptions that free-operant responding occurs in bursts
      with a constant tempo, alternating with periods of engagement in other
      activities; that the durations of bursts and other activities are exponentially
      distributed; and that the rates of initiating and terminating bursts are
      inversely related. The expression provides a satisfactory account of the data of
      three experiments.

PMID- 16812188
TI  - Economic concepts for the analysis of behavior.
AB  - A review of the relationship between schedule of reinforcement, response rate,
      and choice suggests that certain unifying concepts from economics can contribute
      to a more complete science of behavior. Four points are made: 1) a behavioral
      experiment is an economic system and its characteristics-open or closed-can
      strongly determine the results; 2) reinforcers can be distinguished by a
      functional property called elasticity; 3) reinforcers may interact as complements
      as well as substitutes; 4) no simple choice rule, such as strict matching, can
      account for all choice behavior.

PMID- 16812189
TI  - Reinforcement of human observing behavior by a stimulue correlated with
      extinction or increased effort.
AB  - Young men pulled a plunger on mixed and multiple schedules in which periods of
      variable-interval monetary reinforcement alternated irregularly with periods of
      extinction (Experiment 1), or in which reinforcement was contingent on different
      degrees of effort in the two alternating components (Experiment 2). In the
      baseline conditions, the pair of stimuli correlated with the schedule components
      could be obtained intermittently by pressing either of two observing keys. In the
      main conditions, pressing one of the keys continued to produce both
      discriminative stimuli as appropriate. Pressing the other key produced only the
      stimulus correlated with variable-interval reinforcement or reduced effort;
      presses on this key were ineffective during periods of extinction or increased
      effort. In both experiments, key presses producing both stimuli occurred at
      higher rates than key presses producing only one, demonstrating enhancement of
      observing behavior by a stimulus correlated with the less favorable of two
      contingencies. A control experiment showed that stimulus change alone was not an
      important factor in the maintenance of the behavior. These findings suggest that
      negative as well as positive stimuli may play a role in the conditioned
      reinforcement of human behavior.

PMID- 16812190
TI  - Alternative reinforcement effects on fixed-interval performance.
AB  - Pigeons' key pecks were reinforced with food on a fixed-interval schedule. Food
      also was available at variable time periods either independently of responding or
      for not key pecking (a differential-reinforcement-of-other-behavior schedule).
      The latter condition arranged reinforcement following the first pause of t
      seconds after it became available according to a variable-time schedule. This
      schedule allowed separation of the effects of pause requirements </= five-seconds
      and reinforcement frequency. The time spent pausing increased as the duration of
      the pause required for reinforcement increased from 0 to 30 seconds and as the
      frequency of reinforcement for pausing increased from 0 to 2 reinforcers per
      minute. Key pecking was more evenly distributed within each fixed interval with
      shorter required pauses and with more frequent reinforcement for pausing. The
      results complement those obtained with other concurrent schedules in which the
      same operant response was reinforced in both components.

PMID- 16812191
TI  - The effect of contingency upon the appetitive conditioning of free-operant
      behavior.
AB  - The problem of maintaining independence between response rates and reinforcement
      probabilities when determining the effect of varying the response-reinforcement
      contingency upon free-operant behavior was solved by programming local
      reinforcement probabilities for response and no response on a second-by-second
      basis. Fifty-seven rats were trained to lever-press on schedules of water
      reinforcement involving different values of contingency. All rats were first
      trained on a high positive contingency and then shifted to less positive, zero,
      or negative contingencies. Under these conditions, rate of lever-pressing
      declined appropriately when the contingency between response and reinforcement
      decreased or was made negative. The decline in rate produced by a zero
      contingency cannot be attributed to extinction, since the probability of
      reinforcement given the occurrence of a response was the same as for the positive
      contingency from which the shift to zero was made. That is, there was no change
      in the opportunity for response-reinforcement contiguity. It was concluded that
      the technique of programming local reinforcement probabilities offers promise for
      more critical examinations of the effects of contingency upon free-operant
      behavior.

PMID- 16812192
TI  - Mirror pecking and timeout under a multiple fixed-ratio schedule of food
      delivery.
AB  - Pigeons were trained to peck a key under a multiple fixed-ratio 25 fixed-ratio
      175 schedule of food presentation. In the first condition, either a mirror or the
      opportunity to produce a 30-second timeout were available. In a second condition,
      mirror and timeout availability were reversed for the two groups. Following a
      return to the initial condition, mirror and timeout keys were presented together
      for all birds. Mirror and timeout responses occurred predominantly in the pause
      in the larger fixed-ratio component, regardless of whether the opportunities for
      the two responses were available singly or together. Mirror responding occurred
      in a greater proportion of the pauses than did timeouts. When the opportunities
      for both mirror pecking and timeout were available concurrently, they occurred
      with probabilities similar to those under the single conditions. Within the pause
      itself, mirror responses most frequently occurred immediately after
      reinforcement. Timeouts occurred most frequently toward the end of the pause, and
      some timeouts occurred in the early part of the run. Longer preratio pausing
      occurred in the larger fixed-ratio component in the conditions in which the
      mirror was present, whether or not any mirror pecks were recorded.

PMID- 16812193
TI  - Concurrent avoidance of shocks by pigeons pecking a key.
AB  - Three pigeons were studied on concurrent, unsignaled, avoidance schedules in a
      two-key procedure. Shock-shock intervals were two seconds in both schedules. The
      response-shock interval on one key was always 22 seconds, while the response
      shock interval associated with the other key was varied from 7 to 52 seconds in
      different experimental conditions. Response rates on the key associated with the
      varied schedule tended to decrease when the response-shock interval length was
      increased. Responding on the key associated with the constant schedule was not
      systematically affected.

PMID- 16812194
TI  - Acquisition and maintenance of trusting behavior.
AB  - This study determined whether a two-person exchange situation contained natural
      contingencies for trusting behavior or whether external contingencies were
      necessary. Pairs of college students worked matching-to-sample problems for
      money. On each trial there was one problem and the subjects determined which of
      them would solve it. Trusting behavior was defined as an increase in the number
      of consecutive problems each subject allowed his partner to work during sessions
      that also ended with an equitable distribution. Simply, trust was a temporary
      deviation from equity. A subject could give the problem to the other person
      (cooperate), or not respond and let the other person take the problem (share).
      Other possibilities were for both subjects to try to take the problem (complete),
      or for neither subject to respond and thereby let the person who worked the last
      problem also work the next one (passive trust). When only four lever pulls were
      required to distribute a problem (no external contingencies to reach either
      equity or trust) subjects reached equity, but only minimal trust (strict
      alternation of single problems) developed in 18 sessions. When 30 or 60 lever
      pulls were required to distribute a problem (smaller response requirement for
      passive trust and therefore a contingency for trust), trusting behavior developed
      after a few sessions (fixed ratio 30) or after several trials of the first
      session (fixed ratio 60) and it ordinarily expanded gradually to 10 to 15
      consecutive problems through passive trust. The aversiveness of the inequity
      involved in trusting appears to necessitate a contingency for acquisition. Once
      trust develops, however, this aversiveness is reduced as subjects learn the
      inequity is only temporary (e.g., once trust was acquired at fixed ratio 60 it
      was maintained at fixed ratio 4, which would not initially produce it), and the
      direction of the inequity appears to become of questionable importance (e.g.,
      being behind was alternated over rather than within sessions and usually not in a
      systematic manner).

PMID- 16812195
TI  - On the exponent in the "generalized" matching equation.
AB  - A power function equation between ratios of behavior and ratios of reinforcement
      rates has been called a generalized form of Herrnstein's (1961) matching law,
      even without a formal relationship having been shown between the two equations.
      The present work uses a functional relationship to prove that when ratios of
      reinforcement are not equivalent to ratios of behavior, and the transform leading
      to this inequality is consistent for every pair of reinforcement rates, the
      result is a power function relationship between response and reinforcement
      ratios. The label "generalized matching equation" for the power function equation
      is thus validated formally.

PMID- 16812196
TI  - Discrete-trial choice in pigeons: Effects of reinforcer magnitude.
AB  - The preference of pigeons for large reinforcers which occasionally followed a
      response versus small reinforcers which invariably followed a response was
      studied in a discrete-trial situation. Two differently colored keys were
      associated with the two reinforcement alternatives, and preference was measured
      as the proportion of choice trials on which the key associated with uncertain
      reinforcement was pecked. A combination of choice and guidance trials insured
      that received distributions of reinforcement equalled the scheduled
      distributions. For five of six subjects, preference for the uncertain reinforcer
      appeared to be a linear function of the magnitude of the certain reinforcer. In
      addition, there was greater preference for the response alternative associated
      with uncertain reinforcement than would be expected on the basis of net
      reinforcer value.

PMID- 16812197
TI  - Self-control in pigeons under the Mischel paradigm.
AB  - Walter Mischel studied self-control in preschool children in the following
      manner: if the child waited for an interval to end, he or she received the more
      preferred of two reinforcers; if the child responded to terminate the interval by
      ringing a bell, the less preferred reinforcer was given. We used an analogous
      procedure to study self-control in pigeons: if the bird waited for a trial to
      end, it received the more preferred reinforcer; if the bird terminated the trial
      by pecking a key, the less preferred reinforcer was given. We explored the
      effects on self-control of a number of variables analogous to those studied by
      Mischel and co-workers, e.g., presence versus absence of reinforcers, of
      alternative responses, and of stimuli during the wait interval; prior experience
      of the subjects; and test paradigm. The results obtained with pigeons paralleled
      the results obtained by Mischel with human children.

PMID- 16812198
TI  - Burying by rats in response to aversive and nonaversive stimuli.
AB  - Previous investigations have shown that rats bury a variety of conditioned and
      unconditioned aversive stimuli. Such burying has been considered as a species
      typical defensive reaction. In the present studies, rats buried spouts filled
      with Tabasco sauce, or condensed milk to which a taste aversion was conditioned,
      but did not bury water-filled spouts or spouts filled with a palatable novel food
      (apple juice) to which a taste aversion was not conditioned. However, in other
      experiments rats consistently and repeatedly buried Purina Rat Chow, Purina Rat
      Chow coated with quinine, and glass marbles. This indicates that a variety of
      stimuli, not all aversive or novel, evoke burying by rats. Whereas the behavior
      may reasonably be considered as a species-typical defensive behavior in some
      situations, the wide range of conditions that occasion burying suggests that the
      behavior has no single biological function.

PMID- 16812199
TI  - Effects of variations in local reinforcement rate on local response rate in
      variable interval schedules.
AB  - Rats trained to lever press for sucrose were exposed to variable-interval
      schedules in which (i) the probability of reinforcement in each unit of time was
      a constant, (ii) the probability was high in the first ten seconds after
      reinforcement and low thereafter, (iii) the probability was low for ten seconds
      and high thereafter, (iv) the probability increased with time since
      reinforcement, or (v) the probability was initially zero and then increased with
      time since reinforcement. All schedules generated similar overall reinforcement
      rates. A peak in local response rate occurred several seconds after reinforcement
      under those schedules where reinforcement rate at this time was moderate or high
      ([i], [ii], and [iv]). Later in the inter-reinforcement interval, local response
      rate was roughly constant under those schedules with a constant local
      reinforcement rate ([i], [ii], and [iii]), but increased steadily when local
      reinforcement rate increased with time since reinforcement ([iv] and [v]).
      Postreinforcement pauses occurred on all schedules, but were much longer when
      local reinforcement rate was very low in the ten seconds after reinforcement
      ([iii]). The interresponse time distribution was highly correlated with the
      distribution of reinforced interresponse times, and the distribution of
      postreinforcement pauses was highly correlated with the distribution of
      reinforced postreinforcement pauses on some schedules. However, there was no
      direct evidence that these correlations resulted from selective reinforcement of
      classes of interresponse times and pauses.

PMID- 16812200
TI  - An interresponse time analysis of variable-ratio punishment.
AB  - An interresponse time analysis was used to study the effects of variable-ratio
      punishment schedules on the temporal pattern of reinforced responding. Twelve
      pigeons responded on a baseline variable-interval schedule of food reinforcement.
      A variable-ratio ten schedule of electric shock punishment was then introduced.
      The shock intensity was systematically increased to the highest intensity at
      which responding could be maintained. At this intensity, the mean variable-ratio
      value was increased and then decreased. Variable-ratio punishment resulted in an
      increased relative frequency of very short unreinforced interresponse times
      (response bursting). Increased response bursting accounted for instances of
      response rate facilitation. In addition, shock was followed by interresponse
      times of decreasing mean length over the first several responses after shock.

PMID- 16812201
TI  - Behavioral contrast and the automaintained key peck.
AB  - In two experiments behavioral contrast was demonstrated during discrimination
      training in a positive automaintenance procedure. During the baseline condition
      in each experiment, a key was transilluminated for eight seconds by one of two
      colors (CS) following a variable intertrial interval signaled by a dark key.
      Keylight transillumination terminated with a response-independent food
      presentation. In the first experiment, food was eliminated during one CS for up
      to fifty sessions. After reinstatement of food following each CS, the
      discrimination was reversed. Six of the eight subjects showed positive behavioral
      contrast, i.e., response rates increased during the CS associated with food as
      they decreased during the CS associated with no food. The effect was replicated
      in Experiment II, but it did not occur when both the food and its associated CS
      were eliminated. These results were comparable to those obtained with operant
      discrimination training procedures (behavioral contrast) and with Pavlovian
      discrimination training. The results suggest that additivity theories of
      behavioral contrast may be insufficient to account for these data.

PMID- 16812202
TI  - Differential responding without differential reinforcement: Intensity difference,
      continuum position, and reinforcement density effects.
AB  - The response rates of five groups of rats were observed during exposure to
      different intensities of a four kilohertz tone within a two-component multiple
      schedule of nondifferential reinforcement. Response rates were found to be higher
      during the multiple schedule component which contained the higher intensity tone.
      Larger differences in response rates between the two multiple schedule components
      occurred with greater intensity separations (30 versus 20 decibels). At the 30
      decibel separation a low absolute magnitude produced larger response rate
      differences than a high absolute magnitude, while at the 20 decibel separation a
      high absolute magnitude produced larger response rate differences. Increases in
      reinforcement density were accompanied by decreases in response rate differences
      between high and low intensity components only when over-all response rates also
      increased.

PMID- 16812203
TI  - The delay-reduction hypothesis of conditioned reinforcement and punishment:
      Observing behavior.
AB  - Pigeons responded in an observing-response procedure in which three fixed
      interval components alternated. Pecking one response key produced food
      reinforcement according to a mixed schedule. Pecking the second (observing) key
      occasionally replaced the mixed-schedule stimulus with the stimulus correlated
      with the fixed-interval component then in effect. In Experiment 1, observing was
      best maintained by stimuli correlated with a reduction in mean time to
      reinforcement. That finding was consistent with the conditioned-reinforcement
      hypothesis of observing behavior. However, low rates of observing were also
      maintained by stimuli not representing delay reduction. Experiment 2 assessed the
      role of sensory reinforcement. It showed that response rate was higher when
      maintained by stimuli uncorrelated with reinforcement delay than when the stimuli
      were correlated with a delay increase. This latter result supports a symmetrical
      version of the conditioned-reinforcement hypothesis that requires suppression by
      stimuli correlated with an increase in time to reinforcement. The results were
      inconsistent with hypotheses stressing the reinforcing potency of uncertainty
      reduction.

PMID- 16812204
TI  - Delay or rate of food delivery as determiners of response rate.
AB  - PIGEONS WERE CONFRONTED WITH TWO KEYS: a green food key and a white changeover
      key. Food became available for a peck to the green key after variable intervals
      of time (mean = 113 seconds). A single peck on the changeover key changed the
      color of the food key to red for a fixed period of time during which the timing
      of the variable-interval schedule in green was suspended and the switching option
      eliminated and after which the conditions associated with green were reinstated.
      In Experiment 1 a single food presentation was obtainable during each red-key
      period after a minimum delay timed from the switch. This delay and the duration
      of the red-key period were held constant during a condition but varied between
      conditions (delay = 2.5, 7.5, 15, or 30 seconds; red-period duration = 30, 60,
      120, 240, or 480 seconds). In Experiment 2 additional food presentations were
      scheduled during a 240-second red-key period with the delay to the first food
      delivery held constant at 30 seconds, and the delays to later food deliveries
      varied over conditions. Considering the data from both experiments, the rate of
      switching to red was a decreasing function of the delay to the first food, the
      delay to the second food, and perhaps the delay to the third food after a switch.
      There was no clear evidence that the rate of food in the red-key period made an
      independent contribution. The ordering of response rates among conditions was
      consistent with the view that each food presentation after a response adds an
      incremental effect to the rate of the response and that each food presentation's
      contribution is a decreasing function of its delay timed from the response.

PMID- 16812205
TI  - A comparison of signaled and unsignaled delay of reinforcement.
AB  - Pigeons were trained on either a variable-interval 60-second schedule, or on a
      schedule that differentially reinforced responses that were spaced at least 20
      seconds apart. The birds were then exposed to several durations of reinforcement
      delay, with comparisons between signaled and unsignaled delays. Although
      unsignaled delays of 5 and 10 seconds produced large decreases in response rate,
      signaled delays of up to 10 seconds produced only moderate decreases in response
      rates. In addition, some subjects responded more rapidly with a .5 or 1.0 second
      duration of unsignaled delay than with immediate reinforcement. These response
      rate changes occurred regardless of whether the rate of reinforcement
      concomitantly decreased or increased.

PMID- 16812206
TI  - Effect of delay-interval stimuli on delayed symbolic matching to sample in the
      pigeon.
AB  - In Experiment 1, food-deprived pigeons received delayed symbolic matching to
      sample training in a darkened Skinner box. Trials began with the illumination of
      the grain feeder lamp (no food sample), or illumination of this lamp, accompanied
      by the raising of the feeder tray (food sample). After a delay of a few seconds,
      the two side response keys were illuminated, one with red and one with green
      light, with positions counterbalanced over trials. Pecking the red (green)
      comparison produced grain reinforcement if the trial had started with food (no
      food); pecking red after a no-food sample or green after a food sample was not
      reinforced. Once matching performance was stable, four stimuli were presented
      during the delay interval, and their effects on matching accuracy were evaluated.
      Both illumination of the houselight and the center key with white geometric forms
      decreased matching accuracy, whereas presentation of a tone and vibration of the
      test chamber did not. In Experiment 2, pecking the red center key was reinforced
      with food according to a variable interval schedule. The effects of occasional
      brief presentations of the four stimuli used in the first experiment on ongoing
      pecking were assessed. The houselight and form disturbed key pecking, but the
      tone and vibration did not. Thus, stimuli that interfered with delayed matching
      also interfered with simple operant behavior. Implications of these results for
      theories of remembering are discussed.

PMID- 16812207
TI  - Determinants of contrast in the signal-key procedure: Evidence against additivity
      theory.
AB  - Two experiments are reported that challenge the interpretation of previous
      results with the signal-key procedure, in which the discriminative stimuli are
      located on a response key different from the key associated with the operant
      response requirement. Experiment 1 replicated the procedure of Keller (1974), and
      found that contrast effects on the operant key occurred reliably for only one of
      four subjects. High rates to the signal key initially occurred for only one
      subject, but modifications of the procedure produced substantial rates to the
      signal key for all subjects. In all cases, however, signal-key behavior was
      greatly reduced by the addition of a changeover delay which prevented
      reinforcement within 2 seconds of the last peck to the signal key, suggesting
      that signal-key pecking was maintained primarily by adventitious reinforcement.
      Experiment 2 modified the signal-key procedure by using three response keys, so
      that the discriminative stimuli on the signal key controlled different responses
      during all phases of training. With this modification, reliable contrast effects
      on the operant key occurred for all subjects, suggesting that the failure to find
      contrast in previous studies has been due to the confounding of changes in the
      discrimination requirements with changes in relative rate of reinforcement. The
      results challenge the additivity theory of contrast, and suggest that "elicited"
      behavior plays a minor role, if any, in the determination of contrast effects in
      multiple schedules.

PMID- 16812208
TI  - Generalization peak shift in rats under conditions of positive reinforcement and
      avoidance.
AB  - Rats were trained to discriminate between two click frequencies. One frequency
      was associated with either variable-interval food reinforcement (Experiment 1) or
      free-operant avoidance (Experiment 2). The other frequency was associated with
      the absence of food in Experiment 1 and the absence of shock in Experiment 2. On
      a click frequency generalization test, the rats in both experiments showed
      positive peak shift with the shape of the relative gradients being very similar.
      This is the first reported instance of peak shift in rats when responding was
      maintained by an avoidance contingency. Nondifferentially trained controls showed
      that this shift was due exclusively to associative processes, with nonassociative
      stimulus factors in themselves apparently making no contribution to increased
      rates at particular stimulus values. These results show the comparability of
      appetitive and aversive control and support the position that gradient
      differences do not result from approach versus avoidance per se.

PMID- 16812209
TI  - Choosing schedules of signaled appetitive events over schedules of unsignaled
      ones.
AB  - Two experiments were completed allowing albino rats to choose between signaled
      and unsignaled reward conditions. These experiments examined the effects on
      preference of (1) response dependent versus response-independent reward and, (2)
      food pellets versus chocolate milk as the reward. All subjects preferred the
      signaled condition over the unsignaled condition, whether exposed to response
      dependent, or to response-independent delivery of rewards. Preference was
      controlled most effectively by presenting both the signal itself and the
      correlated stimulus identifying the signaled condition. The signal presented
      alone (Extinction 3) controlled preference more effectively than did the stimulus
      correlated with the signaled condition (Extinction 2). The second experiment
      showed that the quality of the reinforcer (pellets and chocolate milk) did not
      affect preference for signaled reward since all subjects preferred the signaled
      condition at levels comparable to those observed in Experiment 1, with food
      pellets. These results, along with others, argue against species differences,
      response-dependency, and reinforcer quality as variables affecting the direction
      of preference.

PMID- 16812210
TI  - Effects of signaled and unsignaled shock on schedule-controlled lever pressing
      and schedule-induced licking: Shock intensity and body weight.
AB  - Schedule-controlled lever pressing and schedule-induced licking were studied in
      rats under a multiple fixed-interval fixed-interval schedule of food
      reinforcement. Following acquisition of stable rates of pressing and licking, a
      multiple variable-time variable-time schedule of electric-shock delivery was
      superimposed upon the baseline schedule. In only one component of the multiple
      schedule, a 5-sec stimulus preceded each shock (signaled shock). In the other
      component shock was unsignaled. Several shock intensities (Experiment 1) and body
      weights (Experiment 2) were studied. Lever pressing and licking were affected
      similarly by experimental manipulations, although with parametric differences.
      Depending upon shock intensity and body weight, rates of lever pressing and
      licking were hardly suppressed, suppressed primarily in the unsignaled shock
      component (differential suppression), or markedly suppressed in both components.
      Differential suppression during components with signaled and unsignaled shock and
      conditioned suppression of responding during the preshock stimulus appeared not
      to be functionally related. Differential suppression depended more on the
      discriminability of shock-free time, and on shock intensity, body weight, and the
      type of response than on the "preparatory" behavior preceding shock.

PMID- 16812211
TI  - Effects of chlordiazepoxide and d-amphetamine on responding suppressed by
      conditioned punishment.
AB  - Key pecking by two pigeons, maintained under a variable-interval two-minute
      schedule of food presentation, was suppressed when each response produced a five
      second visual stimulus that was occasionally paired with shock. Stimulus-shock
      pairings occurred independently of responding according to a variable-time six
      minute schedule for one bird or once per session for the other bird. The effects
      of chlordiazepoxide and d-amphetamine were assessed on this baseline of behavior
      suppressed by conditioned punishment. Chlordiazepoxide produced dose-related
      increases in the rate of punished responding, whereas d-amphetamine produced only
      decreases. In addition, chlordiazepoxide produced dose-related increases in
      response rate during the response-produced and response-independent stimulus
      presentations; d-amphetamine, however, only decreased responding during stimulus
      presentations.

PMID- 16812212
TI  - Effects of instructional constraints on human fixed-interval performance.
AB  - Several groups of human subjects were exposed to a variety of experimental
      conditions involving a fixed-interval 27-second schedule of reinforcement in
      compound with instructions to constrain in the number of responses within the
      interreinforcement interval and/or the duration of the experimental session. One
      group was further exposed to a contingency involving the placement of responses
      within the IRI. A diversity of patterns of performance was observed, including
      those typically associated with animal subjects exposed to FI schedules.
      Generally, the imposition of instructions to minimize session duration reduced
      post-reinforcement pausing and increased overall reinforcement density from those
      levels obtained with only instructions to expend a given number of responses per
      reinforcer. The results are seen to underscore the sensitivity of human fixed
      interval performance and the contribution of extra-experimental contingencies.

PMID- 16812213
TI  - Prepositional phrases spoken and heard.
AB  - The relation between verbal and nonverbal behavior with common syntactic
      properties was investigated, using retarded and nonretarded children.
      Reinforcement was contingent on either verbal or nonverbal responses whereas
      responses of the other repertoire had no experimental consequences. Changes
      sometimes occurred in the unreinforced (collateral) repertoire, but they were
      always changes in the stimulus control of pre-existing topographies. A
      contingency involving responses of one repertoire never instated new topographies
      in the collateral repertoire. This suggested that the problem of "cross-modality
      generalization" should be reformulated to distinguish explicitly between
      instating new topographies and changing the stimulus control of pre-existing
      topographies. The result confirmed Skinner's hypothesis about "the same response
      spoken and heard" and clarified some anomalies in previous studies.

PMID- 16812214
TI  - Charles B. Ferster-A personal memoir.

PMID- 16812215
TI  - Relationship between response rate and reinforcement frequency in variable
      interval schedules: II. Effect of the volume of sucrose reinforcement.
AB  - Three rats were exposed to variable-interval schedules specifying a range of
      different reinforcement frequencies, using three different volumes of .32 molar
      sucrose (.10, .05, and .02 milliliters) as the reinforcer. With each of the three
      volumes, the rates of responding of all three rats were increasing, negatively
      accelerated functions of reinforcement frequency, the data conforming closely to
      Herrnstein's equation. In each rat the value of the constant K(H), which
      expresses the reinforcement frequency needed to obtain the half-maximal response
      rate, increased with decreasing reinforcer volume, the values obtained with .02
      milliliters being significantly greater than the values obtained with .10
      milliliters. The values of the constant R(max), which expresses the theoretical
      maximum response rate, were not systematically related to reinforcer volume. The
      effect of reinforcer volume upon the relationship between response rate and
      reinforcement frequency is thus different from the effect of the concentration of
      sucrose reinforcement: In a previous experiment (Bradshaw, Szabadi, & Bevan,
      1978) it was found that sucrose concentration influenced the values of both
      constants, R(max) increasing and K(H) decreasing with increasing sucrose
      concentration.

PMID- 16812216
TI  - Contrast and undermatching as a function of reinforcer duration and quality
      during multiple schedules.
AB  - Eight pigeons pecked keys under multiple variable-interval two-minute variable
      interval two-minute schedules. In Experiment 1, the reinforcers were 2, 4, or 8
      seconds access to a food magazine. In Experiments 2 and 3, the reinforcers were
      grains that had been determined to be most-, moderately-, or non-preferred. Both
      positive and negative behavioral contrast occurred when the reinforcers in one
      component were held constant and the duration or type of reinforcer obtained in
      the other component varied. Undermatching occurred when the relative rate of
      responding during a component was plotted as a function of the relative duration
      of the reinforcers in that component.

PMID- 16812217
TI  - Undermatching and contrast within components of multiple schedules.
AB  - Six multiple variable-interval schedules each comprised one variable-interval
      sixty second component and an alternated component which was varied. Four
      pigeons' responses were recorded in five successive subintervals of each
      component. Response rate changes across subintervals revealed instances of local
      contrast and small local induction effects in the changed component. In the
      constant component, smaller local contrast and larger local induction effects
      obtained. Accordingly, the magnitude of behavioral contrast, defined as an
      inverse relation between response rate in the constant component and
      reinforcement rate in the changed component, did not change reliably across
      subintervals of the constant component. Ratios of response rates in initial
      subintervals were highly sensitive to reinforcement ratios. Sensitivity decreased
      sharply over the first two-fifths of the components and remained constant for the
      remainder. The results demonstrated that changes in multiple schedule sensitivity
      are a function of time since the alternation of successive components.

PMID- 16812218
TI  - The following schedule of reinforcement as a fundamental determinant of steady
      state contrast in multiple schedules.
AB  - Two experiments investigated whether steady-state interactions in multiple
      schedules depend exclusively on the following schedule of reinforcement.
      Experiment 1 used a four-component multiple schedule in which two components were
      associated with the same constant schedule of reinforcement, and where rate of
      reinforcement was varied in the component that followed one of these. Contrast
      effects were reliable only in the component that preceded the point of
      reinforcement variation, although some contrast did occur otherwise. In those
      instances where contrast other than the following-schedule effect did occur, it
      was accounted for by the effect of the preceding schedule, an effect for which
      there were consistent individual differences among subjects, and which varied
      with component duration. Experiment 2 used a three-component schedule, in which
      reinforcement rate was varied in the middle component. The results were
      consistent with Experiment 1, as the following-schedule effect was the only
      consistent effect that occurred, although an effect of the preceding schedule did
      occur for some subjects under some conditions, and was especially evident early
      in training. The conclusion from both experiments is that there is no general
      effect of relative rate of reinforcement apart from the sum of the effects of the
      preceding and following schedules, and that the following-schedule effect is the
      fundamental cause of steady-state interactions.

PMID- 16812219
TI  - Selective punishment of interresponse times.
AB  - Lever pressing by two squirrel monkeys was maintained under a variable-interval
      60-second schedule of food presentation. When response-dependent electric shock
      was made contingent on comparatively long interresponse times, response rate
      increased, and further increases were obtained when the minimum interresponse
      time requirement was decreased. When an equal proportion of responses produced
      shock without regard to interresponse time, rates decreased. Thus, shock
      contingent on long interresponse times selectively decreased the relative
      frequency of those interresponse times, and increased the relative frequency of
      shorter interresponse times, whereas shock delivered independent of interresponse
      times decreased the relative frequency of shorter interresponse times while
      increasing the frequency of longer ones. The results provide preliminary evidence
      that interresponse times may be differentiated by punishment, further supporting
      the notion that interresponse times may be considered functional units of
      behavior.

PMID- 16812220
TI  - Responding under sequence schedules of electric shock presentation.
AB  - Lever pressing by squirrel monkeys was examined under second-order schedules of
      electric shock presentation in which different discriminative stimuli were
      associated with consecutive components (sequence schedules). Components were
      always two-minute fixed-interval schedules, and three different overall schedules
      were studied. Under an overall eight-minute fixed-interval schedule, the first
      component completion after at least eight minutes had elapsed produced electric
      shock. The number of components actually completed ranged from one to four; thus,
      different discriminative stimuli were occasionally associated with electric shock
      presentation. Under an overall "yoked" variable-ratio schedule, electric shock
      was presented after completion of a variable number of components; the required
      number and the distribution of components were matched to those obtained under
      the overall eight-minute fixed-interval schedule. Under an overall fixed-ratio
      schedule, electric shock was presented after completion of four components
      (chained schedule). Under all three sequence schedules, responding in early
      components was characterized by a pause followed by a single response after the
      end of the two-minute interval; responding in later components was characterized
      by a shorter pause followed by positively accelerated responding. Manipulation of
      overall schedules of shock presentation in these complex behavioral situations
      produced changes in responding comparable to those ordinarily obtained after
      similar manipulation of dependencies under both single and second-order schedules
      of food presentation. These experiments extend the range of conditions and levels
      of complexity under which responding can be maintained by presentation of
      electric shock.

PMID- 16812221
TI  - Introduction.

PMID- 16812222
TI  - Paired baseline performance as a behavioral ideal.
AB  - Several recent theories view performance under the constraints of a schedule as
      an attempt to approach the basepoint, the total amount of the instrumental
      response and the total amount of the contingent response seen in the absence of
      schedule constraint. Some new analyses of experiments on concurrent ratio
      schedules, and simple ratio schedules offering an optional magnitude of
      contingent reward, tested this view directly. In each of the five experiments
      examined the organism rejected the chance of a closer approach to the basepoint,
      and thereby failed in addition to maximize the rate of reinforcement.

PMID- 16812223
TI  - How to maximize reward rate on two variable-interval paradigms.
AB  - Without assuming any constraints on behavior, we derive the policy that maximizes
      overall reward rate on two variable-interval paradigms. The first paradigm is
      concurrent variable time-variable time with changeover delay. It is shown that
      for nearly all parameter values, a switch to the schedule with the longer
      interval should be followed immediately by a switch back to the schedule with the
      shorter interval. The matching law does not hold at the optimum and does not
      uniquely specify the obtained reward rate. The second paradigm is discrete trial
      concurrent variable interval-variable interval. For given schedule parameters,
      the optimal policy involves a cycle of a fixed number of choices of the schedule
      with the shorter interval followed by one choice of the schedule with the longer
      interval. Molecular maximization sometimes results in optimal behavior.

PMID- 16812224
TI  - Optimal choice.
AB  - We present a classification and theoretical analysis of discrete-trial and free
      operant choice procedures in which reinforcement is assigned to one alternative
      only, or independently to both, is either always available or conditionally
      available, and is either "held" or not from trial to trial. Momentary-maximizing
      and (globally) optimal choice sequences are defined in terms of initializing and
      marker events. Free-operant choice is analyzed in terms of a clock space whose
      axes are the times since the last A and B choices. The analysis shows that most
      molar matching data are derivable from momentary maximizing, and that the
      momentary-maximizing hypothesis has not been adequately tested in either discrete
      trial or free-operant situations.

PMID- 16812225
TI  - Wilkinson's method of estimating the parameters of Herrnstein's hyperbola.

PMID- 16812226
TI  - Escape from freedom: Choosing not to choose in pigeons.
AB  - Preference for the availability of food-reinforcement alternatives was
      investigated with Rachlin and Green's (1972) concurrent-chains self-control
      paradigm. The terminal link of one chain made available a choice between
      immediate access to food for T seconds and delayed access to food for 4 seconds.
      The terminal link of the other chain provided only delayed access to food. When T
      was reduced to .25 seconds, pigeons began to select the delayed-access key in
      both terminal links. Even so, the pigeons strongly preferred constraint over
      choice. This effect could not be accounted for by differences in the actual
      amount of food obtained in the terminal links, by avoidance of the immediate
      reinforcement key when not presented as part of a choice, or by avoidance of a
      multi-key terminal link. Rather, constraint was preferred over freedom.
      Apparently, the preference for choice is determined by the particular type of
      choice offered.

PMID- 16812227
TI  - The role of intermittent food in the induction of attack in pigeons.
AB  - The present experiments evaluated whether transitions in reinforcer probability
      are necessary to induce attack in pigeons. In Experiment I, three of six pigeons
      exposed to response-contingent constant-probability food schedules and a
      photograph of a conspecific as a target exhibited sustained postreinforcement
      attack on the target. The postreinforcement pattern of attack developed over the
      course of the experiment and was accompanied by a reduction in the rate of
      postreinforcement key pecking and an increase in the postreinforcement pause in
      key pecking. These effects on key pecking resulted in unprogrammed variations in
      the probability of reinforcement which may have been responsible for the
      induction of attack. In Experiment II, the attack-inducing properties of a
      constant-probability response-independent food schedule were compared to a
      periodic food schedule matched for overall rate of food delivery and to a no-food
      condition. In addition to attack, the spatial location of the subjects was
      monitored during each interfood interval. The periodic and aperiodic food
      schedules generated very different patterns of spatial location. Postfood attack
      was induced by both food schedules, although the constant-probability schedule
      induced attack in fewer birds. The no-food condition was not effective in
      inducing attack in any birds. These experiments indicate that intermittent food
      schedules without reductions in reinforcer probability are sufficient to induce
      attack in some pigeons, although not as effective as schedules with transitions
      in reinforcer probability.

PMID- 16812228
TI  - Autoshaping as a psychophysical paradigm: Absolute visual sensitivity in the
      pigeon.
AB  - A classical conditioning procedure (autoshaping) was used to determine absolute
      visual threshold in the pigeon. This method provides the basis for a standardized
      visual psychophysical paradigm.

PMID- 16812229
TI  - Undermatching and overmatching: The fixed-ratio changeover requirement.
AB  - Concurrent variable-interval two-minute and six-minute schedules were arranged
      while the fixed-ratio changeover requirement was varied among one, two, and four
      responses. A four-response requirement produced overmatching in the response and
      time data. A one-response requirement produced consistent undermatching in the
      time data but mixed results in the response data. The two-response requirement
      showed undermatching in the time data and overmatching in the response data. The
      results are discussed in relation to previous research using changeover
      requirements of five and ten responses, which produced clear tendencies toward
      overmatching, especially with response data. Taken together, these findings
      suggest that matching is not a unique result, and that undermatching or
      overmatching can be produced by continuous variation of the changeover
      requirements.

PMID- 16812230
TI  - Conditioned reinforcement as a function of duration of stimulus.
AB  - Pigeons were provided with three keys. Pecking the center key produced grain on a
      schedule that alternated at unpredictable times between a variable-interval
      component and extinction. On concurrent variable-interval schedules, pecking
      either side key produced a stimulus associated with the variable-interval
      component on the center key provided that said schedule was currently in effect.
      The independent variable was the length of time this stimulus remained on the
      keys. Pecking one side key produced the stimulus for 27 seconds, whereas the
      duration produced by pecking the other key varied for successive blocks of
      sessions. For the first four birds, the values tested were 3, 9, 27, and 81
      seconds. For the second group, numbering three birds, the values tested were 1,
      3, 9, and 27 seconds. The dependent variable was the proportion of total side key
      pecks that occurred on the variable key. For all birds, the function was positive
      in slope and negative in acceleration. This finding supports a formulation that
      ascribes the maintenance of observing responses in a normal setting to the fact
      that the subject exposes itself to the positive discriminative stimulus for a
      longer mean duration than it does to the negative stimulus.

PMID- 16812231
TI  - Stimulus control of respondent and operant key pecking: A single key procedure.
AB  - Pigeons' responses to a uniformly illuminated response key were either reinforced
      on a variable-interval one-minute schedule of reinforcement or extinguished for
      one-minute periods. When 1.5 second signals were presented at the beginning of
      each component, so as to differentially predict reinforcement, the pigeons pecked
      at the signals, at rates higher than rates during the remainder of the component.
      When the brief signals were not differentially predictive of reinforcement,
      pecking in their presence decreased to near zero levels. Similar results were
      obtained with signals based upon colors and upon line orientations. Changes in
      rates of (unreinforced) pecking occurred during the signal whether pigeons
      responded differentially during the remainder of the component or not. Experiment
      II demonstrated that the presence of the signal correlated with extinction was
      not necessary for pecking to develop at the signal which preceded the component
      in which responding was intermittently reinforced. The experiments demonstrated a
      clear dissociation of respondent control from operant control of a response. In
      addition, operant behavior was shown to be relatively insensitive to differing
      rates of reinforcement, as compared to the sensitivity of respondent behavior to
      differing rates of reinforcement produced by the very same operant behavior.

PMID- 16812232
TI  - Trace autoshaping: Acquisition, maintenance, and path dependence at long trace
      intervals.
AB  - The pigeon's tendency to acquire and maintain signal-directed key pecking under a
      trace conditioning procedure was parametrically examined. In Experiment 1, the
      percentage of CS trials with a key peck response was a decreasing function of the
      trace interval for separate groups of pigeons. The majority of subjects acquired
      signal-directed key pecking with trace intervals as long as 36 sec. In Experiment
      2, differential maintenance of key pecking occurred across trace intervals in a
      within-subject procedure. Maintenance of key pecking at 36- and 60-sec trace
      intervals was path dependent in that responding depended on the subject's
      performance under the preceding trace interval.

PMID- 16812233
TI  - Autoshaping in the rat: Effects of omission on the form of the response.
AB  - Two experiments were conducted to investigate the effect of an omission
      contingency on behavior related to and characterizing autoshaped lever contacts
      in the rat. In Experiment I an omission contingency imposed on autoshaped lever
      contacts forceful enough to produce a press (.078N) resulted in a significant
      decrease in lever presses, but had no effect on frequency of lever touches
      (contacts of insufficient force to produce a press) or rate of food tray entry
      during lever presentation. In contrast, rats which received a similar number of
      lever-food pairings, but whose behavior had no programmed consequences (yoked
      control subjects), showed an increase in lever press rate, a significant decrease
      in rate of food tray entry, and no change in rate of lever-touches. In Experiment
      II, the effect of a similar omission contingency on the topography of lever
      contact responses was investigated. Prior to omission training subjects contacted
      the lever primarily by pawing it. Following omission training this behavior was
      suppressed, with a subsequent increase in lever contacts characterized as nosing.
      Yoked control subjects showed no significant changes in lever contact topography.
      The results indicate that (1) an omission contingency does not simply eliminate
      wholesale those topographies which incur the contingency but produces subtle
      adaptive changes in lever contact topography; and (2) the nature of the
      autoshaped response in the rat does not appear to be rigid enough to depend
      solely upon the nature of the unconditioned stimulus or the conditioned stimulus,
      but can also be determined by the relationships existing between the animal's
      behavior and these stimuli.

PMID- 16812234
TI  - Dynamic equilibrium on a cyclic-interval schedule with a ramp.
AB  - Five human subjects pressed a panel for money on a cyclic-interval schedule that
      arranged recurring periods of linearly increasing reinforcement rates (ramps).
      Response rate versus time functions for all subjects showed recurring periods of
      linearly increasing response rates. The responding of four of the five subjects
      was in phase with the reinforcement input. The remaining subject showed a two
      minute phase shift. These results suggest that organisms may act like simple
      amplifiers on cyclic-interval schedules, that is, the form of the input signal is
      not changed by the organism, but is returned with amplification. By analogy with
      the variable-interval case, the controlling variable on cyclic-interval schedules
      with rate ramps may be the constant reinforcement acceleration that is arranged
      by the schedule.

PMID- 16812235
TI  - Stimulus generalization of schedule-induced polydipsia.
AB  - Five rats were exposed to an intradimensional discrimination by associating two
      tones of different frequency with the components of a multiple random-time 30
      sec, extinction schedule of food presentation. After schedule-induced polydipsia
      developed and the intermittent schedule of food presentation established stable
      differential licking rates during the stimuli associated with the multiple
      schedule, a stimulus generalization test was conducted. When generalization
      testing was conducted by presenting stimuli that varied on the frequency
      dimension during the random-time 30-sec component of the multiple schedule, all
      five rats demonstrated moderately sloping symmetrical gradients. Thus, schedule
      induced polydipsia can be brought under the control of stimuli other than the
      food pellet.

PMID- 16812236
TI  - Melioration, matching, and maximization.
AB  - Pigeons were studied in an experiment involving two concurrently available
      response keys. Conditions were such that in the first condition the predictions
      of melioration (Herrnstein & Vaughan, 1980), minimization of deviation from
      matching, and maximization were identical: relative time on the right key should
      have fallen between .125 and .25, which in fact occurred. In the second
      condition, melioration predicted a shift in relative time on the right to between
      .75 and .875, which would involve a transient deviation from matching as well as
      a substantial drop in rate of reinforcement. All three birds eventually shifted
      their distribution of behavior to within the range predicted by melioration.

PMID- 16812237
TI  - Reinforcement by an imprinting stimulus versus water on simple schedules in
      ducklings.
AB  - Ducklings (5 to 28 days old) were trained to peck a pole on fixed-ratio, fixed
      interval, and multiple schedules using brief presentation of an imprinting
      stimulus as the response-contingent event. Other ducklings of the same age were
      trained similarly except that reinforcement consisted of access to water. With
      water reinforcement the typical fixed-ratio ("break-run"), fixed-interval
      ("scallop"), and multiple schedule response patterns were readily established and
      consistently maintained. With the imprinting stimulus these schedule effects were
      inconsistent in some subjects and virtually nonexistent in others, despite
      extended training. Schedule control with the imprinting stimulus was not improved
      by the use of a reinforcement signaling procedure which enhances responding
      reinforced by electrical brain stimulation on intermittent schedules. However,
      the overall rates of responding and the extinction functions generated after
      reinforcement with water versus the imprinting stimulus were comparable. These
      findings imply that control by temporal and discriminative stimuli may be
      relatively weak when a young organism's behavior is reinforced by presentation of
      an imprinting stimulus.

PMID- 16812239
TI  - Effects of ratio contingencies on responding maintained by schedules of electric
      shock presentation (response-produced shock).
AB  - Squirrel monkeys' lever pressing was established under fixed-interval schedules
      of electric-shock presentation (response-produced shock). After appropriate
      temporal patterns of lever pressing were engendered, either fixed-ratio schedules
      of shock presentation were added to the fixed interval, or yoked variable-ratio
      schedules were substituted for the fixed-interval schedules. When fixed-ratio
      schedules were added, there was an initial rise in response rate and schedule
      appropriate patterns of responding developed. After many sessions, however,
      responding ceased abruptly, in some cases with remarkable quickness. When
      variable-ratio schedules were substituted, responded declined gradually and
      eventually was poorly maintained. Ratio contingencies may not support responding
      as well as interval contingencies when electric shock is the maintaining event.

PMID- 16812238
TI  - Responding maintained under intermittent schedules of electric-shock
      presentation: "Safety" or schedule effects?
AB  - Four experiments were conducted in which lever pressing by squirrel monkeys was
      maintained under multiple, mixed, or chained schedules of electric-shock
      presentation. In the first two experiments, a multiple schedule was employed in
      which a fixed-interval schedule of shock presentation alternated with a signaled
      two-minute component. Initially, no events were scheduled during the two-minute
      component (a safety period). In the first experiment, the safety period was
      "degraded" by introducing and systematically increasing the frequency of periodic
      shocks presented during that component. In the second experiment, the proportion
      of overall safe time to unsafe time was decreased by decreasing the value of the
      fixed-interval schedule while holding constant shock frequency during the two
      minute component. In the third experiment, the overall arrangement was changed
      from a multiple to a mixed schedule in an attempt to determine whether fixed
      interval responding would be maintained when a single exteroceptive stimulus was
      associated with both components. In the fourth experiment, the overall
      arrangement was changed from a multiple to a chained schedule in an effort to
      determine whether fixed-interval responding would be maintained when its
      consequence was presentation of a signaled "unsafe" period. Fixed-interval
      responding was well maintained under all experimental conditions; the varied
      relationships obtained lend more support to conceptualizations of shock
      maintained behavior as exemplifying schedule-controlled behavior than to
      suggestions that such behavior may be readily accounted for by "safety theory."

PMID- 16812240
TI  - Uninstructed human responding: Sensitivity of low-rate performance to schedule
      contingencies.
AB  - College students' presses on a telegraph key occasionally turned on a light in
      the presence of which button presses produced points later exchangeable for
      money. Initially, responding was maintained by low-rate contingencies
      superimposed on either random-interval or random-ratio schedules. Later, the low
      rate contingencies were relaxed. Low-rate key pressing had been established for
      some students by shaping and for others by demonstration and written
      instructions. After the low-rate contingencies were relaxed, higher response
      rates generally did not increase point earnings with random-interval scheduling,
      but did so with random-ratio scheduling. In both cases, shaped responding usually
      increased, and instructed responding usually continued at an unchanged low rate.
      The insensitivity of instructed responding typically occurred despite contact
      with the contingencies. The differential sensitivity to schedule contingencies of
      shaped responding relative to instructed responding is consistent with the
      different properties of contingency-governed and rule-governed behavior and is
      not rate-dependent.

PMID- 16812241
TI  - Preference for signaled versus unsignaled reinforcement delay in concurrent-chain
      schedules.
AB  - A concurrent-chain schedule was employed to examine pigeons' preferences for
      signaled versus unsignaled delay of reinforcement in which the delay durations
      ranged from zero to ten seconds. In general, pigeons preferred signaled delay
      over unsignaled delay especially when a variable-interval 30-second schedule
      operated in each initial link; when a variable-interval 90-second schedule
      operated in each initial link, these preferences tended toward indifference or
      were attenuated. In addition, prior training seemed to exert partial control over
      behavior. Responding in the terminal link was higher under signaled delay than
      unsignaled delay in a majority of the cases. Moreover, response rates under
      signaled delay remained fairly constant whereas responding under unsignaled delay
      was initially high, but decreased systematically with delay durations as short as
      2.5 seconds. These results are consistent with a number of other studies
      demonstrating the significant role of a signal for impending positive stimuli.

PMID- 16812242
TI  - The role of discriminative stimuli in concurrent performances.
AB  - Key pecking in pigeons was examined under concurrent and parallel arrangements of
      two independent and simultaneously available variable-interval schedules. Pecks
      on the changeover key alternated the schedule of reinforcement for responses on
      the main key. Under concurrent schedules, discriminative stimuli were paired with
      the reinforcement schedule arranged in each component and changeover responses
      also alternated these stimuli. Under parallel schedules, changeover responses
      alternated the effective reinforcement schedule, but did not change the
      discriminative stimulus. On concurrent procedures, changeover response rate was
      inversely related to the difference in reinforcement rate between the two
      components, whereas on parallel schedules no consistent relationship was found.
      With both schedules, absolute response and reinforcement rates were positively
      related, although for a given set of reinforcement frequencies, rates were often
      higher on the concurrent schedules. On concurrent schedules, relative response
      rates and relative times were equal to relative reinforcement rates. On parallel
      schedules these ratios were positively related, but response and time ratios were
      much smaller than were obtained with comparable concurrent schedules. This
      inequality was most pronounced when absolute reinforcement frequencies were
      lowest.

PMID- 16812243
TI  - Stimulus control of delayed matching in pigeons: Directed forgetting.
AB  - Pigeons were trained in delayed matching-to-sample with two postsample stimuli. A
      postsample R-cue signaled that a matching choice phase would follow. A postsample
      F-cue signaled that a matching choice phase would not follow. Previous research
      found reduced matching accuracy on F-cued probe trials when comparison stimuli
      were presented in the choice phase. The present four experiments systematically
      varied the events following an F-cue to determine the conditions under which the
      F-cue reduces delayed-matching accuracy. When F-cues and R-cues controlled
      different behavior, matching on probe trials was poor. When both cues controlled
      the same behavior, matching on probe trials was good. This result is best
      explained by the theory that comparison stimuli retrieve the sample
      representation, but only in the behavioral context established by the R-cue. The
      present research supports the view that response-produced stimuli serve a
      contextual role in animal short-term memory.

PMID- 16812244
TI  - Precurrent self-prompting operants in children: "Remembering".
AB  - IN EXPERIMENT I, ONE OF THREE FORMS OF COLLATERAL BEHAVIOR WAS TRAINED:
      Differential collateral behavior specific in form to one of two discriminative
      stimuli; Common collateral behavior of a single form regardless of the stimulus;
      or Nondifferential collateral behavior of either form regardless of the stimulus.
      Children were next given a short-delay matching-to-sample task in which the
      discriminative stimuli served as samples, and the children's previously trained
      collateral behavior terminated the delay and presented the comparison stimuli.
      Subjects engaging in sample-specific collateral behavior immediately acquired
      matching. Subjects engaging in sample-nonspecific collateral behavior failed to
      acquire matching or did so gradually. In Experiment II the minimal delay in the
      matching task was varied in a mixed sequence, first with collateral behavior
      required, and then with collateral behavior prohibited. When emitting collateral
      behavior Common and Nondifferential subjects showed delay-related decrements in
      matching while Differential subjects did not. When not emitting collateral
      behavior all subjects showed delay-related decrements in matching. Common and
      Nondifferential subjects matched more accurately when prohibited from emitting
      collateral behavior. Differential subjects matched more accurately when emitting
      collateral behavior. The results accord with Skinner's (1953, 1968) analysis of
      precurrent operants.

PMID- 16812245
TI  - Stimulus stringing by pigeons.
AB  - Pigeons were trained to peck one, two, three, and then four colors in a
      predetermined sequence from a five-key array where, over trials, each color
      appeared equally often in each position of the array. Incorrect pecks resulted in
      a buzzer and trial termination, with the same array presented for the next trial.
      Correct pecks produced feedback and correct strings could produce food. All
      subjects performed at a high level of accuracy with no difference at asymptote
      between a continuous and a mixed spectral sequence as the required order.
      Transfer to a new set of arrays had little effect on accuracy. Errors forward in
      the sequence had the highest probability, followed by repeat errors, backward
      errors, and dark-key errors. Some arrays had a higher level of accuracy than
      others but a corresponding systematic variable could not be identified.

PMID- 16812246
TI  - The effects of modifying consummatory behavior on the topography of the
      autoshaped pecking response in pigeons.
AB  - The autoshaped responses of two debeaked pigeons that had developed modified
      eating behavior were compared to the autoshaped responses of three control
      subjects that ate grain normally. The control subjects exhibited keylight
      responding that was judged normal by two independent raters. The debeaked
      subjects pecked the key and ate grain with both normal and modified responses.
      The results of this study demostrate that an autoshaping procedure using grain as
      an appetitive stimulus may be used to establish a response that is not
      biologically preorganized.

PMID- 16812247
TI  - Three versions of the additive theories of behavioral contrast.
AB  - The additive theories of behavioral contrast state that contrast will occur only
      when two types of responses interact during multiple schedules. Three more
      specific versions of the theories may be defined according to how they
      distinguish these two types of responses. A strong version physically
      distinguishes them. A second version distinguishes them according to the
      theoretical processes which control them. A weak version distinguishes them on
      the basis of the environmental relations which control them. Only the weak
      version of the theories is currently testable. The weak theory should be tested
      by establishing each of the two environmental relations independently and then
      combining them to assess their effect on behavior. Because this test is not
      usually performed, many of the results which have been taken to support or
      contradict the additive theories are actually ambiguous.

PMID- 16812249
TI  - Memorial resolution by the board of directors of the society for the experimental
      analysis of behavior.

PMID- 16812248
TI  - Charles Bohris Ferster (1922-1981): An appreciation.

PMID- 16812250
TI  - Concurrent fixed-interval variable-ratio schedules and the matching relation.
AB  - Five rats responded under concurrent fixed-interval variable-ratio schedules of
      food reinforcement. Fixed-interval values ranged from 50-seconds to 300-seconds
      and variable-ratio values ranged from 30 to 360; a five-second changeover delay
      was in effect throughout the experiment. The relations between reinforcement
      ratios obtained from the two schedules and the ratios of responses and time spent
      on the schedules were described by Baum's (1974) generalized matching equation.
      All subjects undermatched both response and time ratios to reinforcement ratios,
      and all subjects displayed systematic bias in favor of the variable-ratio
      schedules. Response ratios undermatched reinforcement ratios less than did time
      ratios, but response ratios produced greater bias than did time ratios for every
      subject and for the group as a whole. Local rates of responding were generally
      higher on the variable-ratio than on the fixed-interval schedules. When
      responding was maintained by both schedules, a period of no responding on either
      schedule immediately after fixed-interval reinforcement typically was followed by
      high-rate responding on the variable-ratio schedule. At short fixed-interval
      values, when a changeover to the fixed-interval schedule was made, responding
      usually continued until fixed-interval reinforcement was obtained; at longer
      values, a changeover back to the variable-ratio schedule usually occurred when
      fixed-interval reinforcement was not forthcoming within a few seconds, and
      responding then alternated between the two schedules every few seconds until
      fixed-interval reinforcement finally was obtained.

PMID- 16812251
TI  - The effects of brief-stimulus presentations in fixed-ratio second-order
      schedules.
AB  - Pigeons' responses were reinforced according to a three-component multiple
      schedule. In Component 1, key pecks produced food according to a fixed-ratio
      second-order schedule with fixed-ratio units. Here, a fixed number of fixed-ratio
      units produced food, and the brief stimulus terminating each unit also
      accompanied food. Responses in Component 2 produced food on an identical schedule
      except that the brief stimulus was not paired with food. Component 3 contained a
      simple fixed-ratio schedule whose response requirement equaled that of Components
      1 and 2. Across conditions the size of the fixed-ratio unit (five, ten, twenty,
      forty, and eighty responses) and the total number of responses per reinforcement
      were parametrically manipulated. The highest response rates and shortest preratio
      pauses were observed in Component 3 (no brief stimulus). The lowest rates and
      longest pauses were found in the component with paired brief-stimulus
      presentations, indicating that the food-paired brief stimulus suppressed
      responding. The suppressive effects were greatest when the fixed-ratio units were
      small (e.g., fixed-ratio 5) and the total fixed-ratio requirement was large
      (e.g., fixed-ratio 160). Under no conditions did the paired brief stimulus
      facilitate responding. The nonpaired brief stimulus also suppressed responding
      but to a lesser extent. The suppressive effects of nonpaired brief stimuli were
      greatest when the fixed-ratio units were small and the total response requirement
      was large. These data suggest that the suppressive effects of the brief stimuli
      may have masked the conditioned-reinforcing effects reported in other studies,
      and that conditions that maximize suppression in second-order schedules involve
      the use of fixed-ratio schedule units and the presentation of many brief stimuli
      per reinforcer.

PMID- 16812252
TI  - Second-order schedules with paired auditory brief stimuli.
AB  - Pigeons were exposed to multiple second-order schedules of paired and unpaired
      brief stimuli in which responding on the main key was reinforced according to a
      fixed-interval thirty-second schedule by a brief stimulus (a tone in the paired
      schedule) and advancement to the next segment of the second-order schedule. In
      Experiment 1, a response on the second key was required during the tone in its
      fourth and final presentation to produce food. Responses during earlier brief
      stimuli indicated the extent to which the final brief stimulus was discriminated
      from preceding ones. Responding was comparable during all tones, extending prior
      findings with visual paired brief stimuli and weakening explanations of subjects'
      failure to discriminate between brief-stimulus presentations in terms of elicited
      responding. In Experiment 2 the number of fixed-interval segments comprising the
      second-order schedules varied from one through eight. Although main-key response
      rates increased across segments in both experiments, they increased much less
      sharply with a variable number of segments. These results suggest that the
      increase in main-key response rates across segments is due primarily to a degree
      of temporal discrimination not reflected on the second key. Main-key response
      rates were higher on paired auditory brief-stimulus schedules than on unpaired
      visual brief-stimulus schedules, especially in Experiment 2, thus further
      extending findings with visual brief stimuli to second-order schedules with
      auditory brief stimuli.

PMID- 16812253
TI  - Effects of fixed-time shocks and brief stimuli on food-maintained behavior of
      rats.
AB  - When a fixed-time schedule of shocks was presented to rats lever pressing for
      food on a random-interval schedule, a pattern of behavior developed with a high
      rate of pressing after shock declining to near zero before the next shock was
      delivered. Once this pattern had stabilized, one-quarter of the shocks were
      replaced with brief auditory stimuli (tones) in a random sequence. Tone
      maintained behavior similar to shock, although tone was never paired with shock.
      Both tone and shocks elicited responding when presented at various times as probe
      stimuli, and responding was usually totally suppressed if neither stimulus
      occurred at the beginning of the fixed-time interval. When other stimuli were
      paired with tone and shock, only those paired with tone gained discriminative
      control and elicited responding. These findings suggest that stimuli that signal
      a shock-free, or safe, period will maintain the pattern of behavior generated by
      shock on a fixed-time schedule. There is a parallel between this phenomenon and
      the control of behavior on second-order schedules of positive reinforcement with
      nonpaired brief stimuli.

PMID- 16812254
TI  - Early and late introduction of probes and stimulus control acquisition in fading.
AB  - College students learned to name Braille patterns presented visually using a
      fading procedure in which Braille patterns were superimposed on letter names
      after which letter names were attenuated. Measurement of acquisition was
      accomplished by presenting probes-consisting of the Braille stimuli only
      throughout fading. Effects of probes upon acquisition were assessed by
      introducing probes early or late in fading. Fewer fading levels were needed for
      Braille elements to acquire control when probes were introduced early rather than
      late. When probes were introduced late, all subjects learned to name the Braille
      elements as the letters were being faded out. When probes were introduced early,
      however, most subjects learned to name the Braille elements as they were being
      faded in. Since virtually no errors occurred during compound-stimulus
      presentations, the probe procedure did not induce errors during acquisition.
      Quantitative analysis of probe data suggested that inclusion of probes enhanced
      the control acquired by the Braille elements during compound-stimulus
      presentations. The reported effects may have been due to differences in the
      relative frequency of reinforcement presented during compounds and probes.

PMID- 16812255
TI  - Optimization and the matching law as accounts of instrumental behavior.
AB  - The interaction between instrumental behavior and environment can be conveniently
      described at a molar level as a feedback system. Two different possible theories,
      the matching law and optimization, differ primarily in the reference criterion
      they suggest for the system. Both offer accounts of most of the known phenomena
      of performance on concurrent and single variable-interval and variable-ratio
      schedules. The matching law appears stronger in describing concurrent
      performances, whereas optimization appears stronger in describing performance on
      single schedules.

PMID- 16812256
TI  - The legacy of Guttman and Kalish (1956): Twenty-five years of research on
      stimulus generalization.
AB  - This paper is a selective review of the methods, problems, and findings in the
      area of operant stimulus generalization over the 25 years since the publication
      of the original paper by Guttman and Kalish (1956) on discriminability and
      spectral generalization in the pigeon. The paper falls into five main sections,
      which encompass the main themes and problems stemming from the Guttman and Kalish
      work and its immediate successors. The first section addresses the relationship
      between stimulus generalization and stimulus control, as well as the variety of
      testing procedures and dependent variables used to measure generalization. The
      next section reviews the limited literature on the effects of early rearing on
      the generalization gradient. The relationship between discriminability among test
      stimuli and the slope of the spectral gradient is discussed in the third section,
      with emphasis upon recent reassessments of the pigeon's hue discriminability
      function. The fourth section reviews the topic of inhibitory stimulus control,
      one which developed with the discovery of the peak shift following
      intradimensional discrimination training. Problems of definition and measurement
      are discussed in conjunction with the gradient forms used to index inhibitory
      control. The last section is devoted to attentional effects and the two principal
      theories postulated to account for them. A survey of different attentional
      paradigms is provided and the possible role of constant irrelevant stimuli as a
      source of control is examined. A brief conclusion summarizes the contribution of
      the generalization technique toward an understanding of the nature and
      acquisition of stimulus control.

PMID- 16812257
TI  - Editorial.

PMID- 16812258
TI  - Choice and multiple reinforcers.
AB  - Pigeons chose between equivalent two-component mixed and multiple terminal-link
      schedules of reinforcement in the concurrent-chains procedure. The pigeons
      preferred the multiple schedule over the mixed when the components of the
      compound schedules were differentiated in terms of density of reinforcement, but
      the pigeons were indifferent when the components were differentiated in terms of
      number of reinforcers per cycle. Taken together, these results indicate that a
      local variable, the interval to the first reinforcer, but not a molar variable,
      the number of reinforcers, was sufficient to differentiate the components and
      thereby evoke preference.

PMID- 16812259
TI  - Changes in a multiple-response repertoire during response-contingent punishment
      and response restriction: Sequential relationships.
AB  - A multiple-response baseline of four activities was established using gerbils as
      subjects. When one of the baseline responses was punished (Experiment 1) or
      restricted (Experiments 2 and 3), only the most probable of the alternative
      baseline responses increased. The response most likely to follow the punished or
      restricted responses during baseline sessions was also suppressed during
      subsequent punishment or response-restriction treatment.

PMID- 16812260
TI  - Effects of prompting and reinforcement of one response pattern upon imitation of
      a different modeled pattern.
AB  - Twelve preschool children participated in a study of the effects of explicit
      training on the imitation of modeled behavior. The responses trained involved a
      marble-dropping pattern that differed from the modeled pattern. Training
      consisted of physical prompts and verbal praise during a single session. No
      prompts or praise were used during test periods. After operant levels of the
      experimental responses were measured, training either preceded or was interposed
      within a series of exposures to modeled behavior that differed from the trained
      behavior. Children who were initially exposed to a modeling session immediately
      imitated, whereas those children who were initially trained immediately performed
      the appropriate response. Children initially trained on one pattern generally
      continued to exhibit that pattern even after many modeling sessions. Children who
      first viewed the modeled response and then were exposed to explicit training of a
      different response reversed their response pattern from the trained response to
      the modeled response within a few sessions. The results suggest that under
      certain conditions explicit training will exert greater control over responding
      than immediate modeling stimuli.

PMID- 16812261
TI  - Preference in concurrent variable-interval fixed-ratio schedules.
AB  - Five pigeons were trained on concurrent variable-interval fixed-ratio schedules
      in three experiments. Experiment 1 used two variable-interval schedules and one
      fixed-ratio schedule, and the ratio requirement was varied. Using the generalized
      matching law, sensitivity to reinforcement was close to 1.0, but performance was
      biased toward the variable-interval schedule with the lower reinforcement rate.
      In Experiment 2, which used one variable-interval and one fixed-ratio schedule,
      the interval schedule was varied. All birds showed sensitivities to reinforcement
      of less than 1.0 and of less than the values obtained in Experiment 1. The
      performance was also biased toward the fixed-ratio schedule. Because the
      generalized matching law could not account for the differences in the data from
      Experiments 1 and 2, an extension of this law was suggested and successfully
      tested in Experiment 3. The proposed dual-sensitivity model was also shown to
      clarify some previously reported results.

PMID- 16812262
TI  - Choice and behavioral patterning.
AB  - Ten pigeons pecked left and right keys in a discrete-trials experiment in which
      access to food was contingent upon changeovers to the right key after particular
      runs of left-key pecks. In each of three sets of conditions, two run lengths were
      reinforced according to a concurrent variable-interval schedule: reinforcement
      followed runs of either 1 or 2, 1 or 4, or 2 or 4 left-key pecks preceding
      changeovers. The intertrial interval separating successive pecks was varied from
      .5 to 10.0 sec, and the relative frequency of reinforcement for the shorter of
      the two reinforced runs was varied from 0 to .75. The contingencies established
      local behavioral patterning that roughly approximated that required for
      reinforcement. For a fixed pair of reinforced run lengths, preference for the
      shorter of the two frequently increased as the intertrial interval increased and
      therefore as the minimum temporal durations of both reinforced runs increased.
      Preference for the shorter of the two also increased as its corresponding
      relative frequency of reinforcement increased. Both of these effects on
      preference were qualitatively similar to corresponding effects in previous
      research with two different kinds of reinforced behavioral patterns,
      interresponse times and interchangeover times. In all these experiments,
      analytical units were found in the temporal patterns of behavior, not in the
      behavior immediately contiguous with a reinforcer. It is suggested that a
      particular local temporal pattern of behavior is established to the extent to
      which it is repeatedly remembered when reinforcers are delivered, regardless of
      whether the delivery of a reinforcer is explicitly contingent upon that pattern.

PMID- 16812263
TI  - Failure to produce response variability with reinforcement.
AB  - Two experiments attempted to train pigeons to produce variable response
      sequences. In the first, naive pigeons were exposed to a procedure requiring four
      pecks on each of two keys in any order, with a reinforcer delivered only if a
      given sequence was different from the preceding one. In the second experiment,
      the same pigeons were exposed to this procedure after having been trained
      successfully to alternate between two specific response sequences. In neither
      case did any pigeon produce more than a few different sequences or obtain more
      than 50% of the possible reinforcers. Stereotyped sequences developed even though
      stereotypy was not reinforced. It is suggested that reinforcers have both hedonic
      and informative properties and that the hedonic properties are responsible for
      sterotyped repetition of reinforced responses, even when stereotypy is negatively
      related to reinforcer delivery.

PMID- 16812264
TI  - Independence of response force and reinforcement rate on concurrent variable
      interval schedule performance.
AB  - Five pigeons were trained over 43 experimental conditions on a variety of
      concurrent variable-interval schedules on which the forces required on the
      response keys were varied. The results were well described by the generalized
      matching law with log reinforcement ratios and log force ratios exerting
      independent (noninteractive) effects on preference. A further analysis using the
      Akaike criterion, an information-theoretic measure of the efficiency of a model,
      showed that overall reinforcement rate and overall force requirement did not
      affect preference. Unlike reinforcement rate changes, force requirement increases
      did not change the response rate on the alternate key, and an extension of
      Herrnstein's absolute response rate function for force variation on a single
      variable-interval schedule is suggested.

PMID- 16812265
TI  - Effects of reinforcer duration on responding in two-link chained interval
      schedules.
AB  - Each of five pigeons was exposed to two or more durations of access to mixed
      grains on two-link, chained, interval schedules in which both links were
      identical fixed-interval or variable-interval schedules. Response rates were an
      increasing function of reinforcer duration for both initial and terminal links.
      For both types of interval schedules, initial-link response rates were more
      sensitive to reinforcer duration than were terminal-link response rates. The
      present results, together with prior ones, suggest that chaining and choice
      procedures are each sufficient for demonstrating substantial sensitivity of
      responding to changes in reinforcer duration.

PMID- 16812266
TI  - Intractable properties of responding under a fixed-interval schedule.
AB  - The behavior engendered by the fixed-interval schedule is characterized by its
      variability within and across intervals. The present experiment was designed to
      assess further the magnitude of interval-to-interval dynamics and to explore
      conditions which might enhance control by response number for subsequent output.
      Pigeons were exposed to three experimental manipulations after responding had
      stabilized under a fixed-interval five-minute schedule. First, a discrete five
      stimulus counter was added so that the key color changed after a fixed number of
      responses. Then additional grain presentations were made at the end of the
      interval so that high response output was differentially reinforced in the
      presence of the counter stimuli. Finally, the counter stimuli were presented as
      an irregular clock (i.e., independently of responding), but the durations were
      yoked to performance under the counter condition. The data show that response
      number can exert influence from one interval to the next, but this source of
      control is weak and not influenced by the experimental manipulations. Results
      from the clock arrangement indicate that behavior is controlled largely by the
      stimulus conditions prevailing at the time of interval onset.

PMID- 16812267
TI  - Human performance on conjunctive fixed-interval fixed-ratio schedules.
AB  - Eighteen young adults performed a lever-pulling task for money. Subjects were
      initially exposed to a fixed-interval 80-second schedule and subsequently to one
      of three conjunctive schedules in which the added fixed-ratio requirement was set
      at either 10, 80, or 120 responses. Three fixed-interval response patterns
      emerged: high constant rate, intermediate rate, or low rate, with most subjects
      displaying the last. Conjunctive performance was related to the subjects' prior
      fixed-interval patterns and the conjunctive ratio requirements. Low-rate subjects
      tended to optimize reinforcement (maximum reinforcers for minimum responses) on
      conjunctive schedules. Response rate was directly related to ratio requirements.
      Subjects' performance closely corresponded to their verbal statements of the
      contingencies.

PMID- 16812268
TI  - Human fixed-interval performance with concurrently programmed schedules: A
      parametric analysis.
AB  - Young adults pressed a lever for points, exchangeable for money, programmed on
      concurrent schedules in which one component was a fixed-interval and the other
      component either a fixed-ratio (Experiment 1) or a differential-reinforcement-of
      low-rate (Experiment 2). Two general patterns of fixed-interval responding,
      postreinforcement pause or constant rate, occurred in both experiments as a
      function of the parameter values of each component. Also patterns of interaction
      between the component schedules developed, in which responding or point delivery
      on one component appeared to be discriminative for responding on the other
      component. Once a pattern of responding was established, it tended to persist
      when the parameter values of the schedule were changed. On many schedules,
      subjects with an experimental history responded differently than did naive
      subjects, although certain schedule values were resistant to the history effects.
      The role of verbal strategies in mediating history effects was discussed.

PMID- 16812269
TI  - Positive and negative contrast as a function of component duration for key
      pecking and treadle pressing.
AB  - Pigeons responded on several multiple schedules for food reinforcers. The
      duration of the components varied from four seconds to 16 minutes. The absolute
      size of positive (Experiment 1) and negative (Experiment 2) behavioral contrast
      varied inversely with component duration when key pecks produced the reinforcers.
      The absolute size of negative contrast varied directly with component duration,
      when treadle presses produced the reinforcers (Experiment 3). These results
      conform to theories that suggest that positive and negative contrast are
      symmetrical when pigeons peck keys. They also conform to theories that suggest
      that the same principles do not govern contrast when pigeons peck keys as when
      they press treadles. Finally, the results support the measurement of behavioral
      contrast by the differences between baseline rates of responding and the rates
      emitted when contrast is present.

PMID- 16812270
TI  - Effects on spelling of training children to read.
AB  - Experiment 1 investigated whether training subjects to read words aloud would
      induce correct written spelling of the words even though spelling had no
      experimental consequences. Training in reading was followed by a weak increment
      in correct spelling. Experiment 2 investigated whether overtraining in reading
      would improve spelling more. Spelling improved as overtraining continued until
      the subjects spelled all the words correctly. Experiments 3 and 4 investigated
      the components of overtraining responsible for this improvement in spelling.
      Initial training in reading followed by repeated opportunities to look at (but
      not say aloud) the printed words resulted in the same gradual improvement in
      spelling as seen in Experiment 2. The results were related to Skinner's theory of
      verbal behavior and to studies of the relationship between speaking and
      instruction-following in children.

PMID- 16812271
TI  - On the analysis of studies of choice.
AB  - In a review of 103 sets of data from 23 different studies of choice, Baum (1979)
      concluded that whereas undermatching was most commonly observed for responses,
      the time measure generally conformed to the matching relation. A reexamination of
      the evidence presented by Baum concludes that undermatching is the most commonly
      observed finding for both measures. Use of the coefficient of determination by
      both Baum (1979) and de Villiers (1977) for assessing when matching occurs is
      criticized on statistical grounds. An alternative to the loss-in-predictability
      criterion used by Baum (1979) is proposed. This alternative statistic has a
      simple operational meaning and is related to the usual F-ratio test. It can
      therefore be used as a formal test of the hypothesis that matching occurs. Baum
      (1979) also suggests that slope values of between .90 and 1.11 can be considered
      good approximations to matching. It is argued that the establishment of a fixed
      interval as a criterion for determining when matching occurs, is inappropriate. A
      confidence interval based on the data from any given experiment is suggested as a
      more useful method of assessment.

PMID- 16812272
TI  - Interval and ratio reinforcement of a complex sequential operant in pigeons.
AB  - Pigeons were required to produce exactly four pecks on each of two keys in any
      order for reinforcement. Correct response sequences were reinforced on either
      fixed-interval two-minute or fixed-ratio four schedules, with each correct
      sequence treated as a single response. Each pigeon developed a particular
      dominant sequence that accounted for more than 80% of all sequences. Sequence
      stereotypy was relatively unaffected by the temporal properties of the fixed
      interval and fixed-ratio schedules. Response time (time from the first response
      in each sequence to the last) was also relatively unaffected by the temporal
      properties of the schedules. In contrast, response latency (time from end of one
      sequence to the beginning of the next) was markedly affected by the schedules.
      Latencies were long early in the interreinforcement interval and got shorter as
      the interreinforcement interval progressed. These data suggest that stereotyped
      response sequences become functional behavioral units, resistant to disruption or
      alteration by reinforcement variables that ordinarily influence the temporal
      spacing of individual responses.

PMID- 16812273
TI  - Some factors that influence the acquisition of complex, stereotyped, response
      sequences in pigeons.
AB  - Two pigeons were required to peck six to nine illuminated response keys. A
      response on any one of the keys darkened that key. When each key had been
      darkened, a reinforcer was delivered. No specific sequence of key pecking was
      ever required. The keys were presented in various matrices: three by two, three
      by three, horizontal rows, and vertical columns. The keys either presented the
      same stimulus, white light; or each key presented a different stimulus, a color
      or form. The results indicated that although there were 720 to 362,880 different
      sequences that would produce reinforcement, each bird developed a particular,
      stereotyped sequence that dominated its behavior. Variability among the birds
      across phases yielded less than 60 sequences, .0001 to 6 percent of the possible
      sequences. The data suggest that a reinforcement contingency that includes "free
      choice" of response sequence will produce stereotypical response sequences that
      function as complex "units" of behavior.

PMID- 16812274
TI  - Choice behavior of rats in a concurrent-chains schedule: Amount and delay of
      reinforcement.
AB  - Rats were exposed to concurrent-chains schedules in which the terminal links were
      equal fixed-interval schedules terminating in one or three food pellets. Choice
      proportions for large reward increased with increases in delay intervals
      programmed on fixed-interval schedules and supported the predictions derived from
      a general choice model originally formulated by Fantino and later developed by
      Navarick and Fantino. In addition, a functional equivalence of two alternatives
      was established by increasing delay intervals with large reward, whereas delay
      intervals for small reward were held constant. Functionally equivalent delay
      intervals with large reward, for each delay interval with small reward, can be
      described by a power function with exponent smaller than 1.0. A better prediction
      of choice proportions resulted when this function was used to derive predicted
      choice proportions.

PMID- 16812275
TI  - Briefly delayed reinforcement: An interresponse time analysis.
AB  - Key-peck responding of pigeons was compared under VI or DRL schedules arranging
      immediate reinforcement and briefly (.5 sec) delayed reinforcement. Delays were
      either signaled by a blackout in the chamber, unsignaled, or unsignaled with an
      additional requirement that responding not occur during the .5 sec interval
      immediately preceding reinforcement (response delay). Relative to the immediate
      reinforcement condition, response rates increased during the unsignaled delay,
      decreased during the signaled delay, and were inconsistent during the response
      delay condition. An analysis of interresponse times (IRTs) under the different
      conditions revealed a substantial increase in the frequency of short (0 to .5
      sec) IRTs during the unsignaled condition and generally during the response delay
      conditions compared to that during the immediate reinforcement baseline. Signaled
      delays decreased the frequency of short (0 to .5 sec) IRTs relative to the
      immediate reinforcement condition. The results suggest that brief unsignaled
      delays and, in many instances, response delays increase the frequency of short
      IRTs by eliminating constraints on responding.

PMID- 16812276
TI  - On the effects of component durations and component reinforcement rates in
      multiple schedules.
AB  - Four experiments, each using the same six pigeons, investigated the effects of
      varying component durations and component reinforcement rates in multiple
      variable-interval schedules. Experiment 1 used unequal component durations in
      which one component was five times the duration of the other, and the shorter
      component was varied over conditions from 120 seconds to 5 seconds. The schedules
      were varied over five values for each pair of component durations. Sensitivity to
      reinforcement rate changes was the same at all component durations. In Experiment
      2, both component durations were 5 seconds, and the schedules were again varied
      using both one and two response keys. Sensitivity to reinforcement was not
      different from the values found in Experiment 1. In Experiment 3, various
      manipulations, including body-weight changes, reinforcer duration changes,
      blackouts, hopper lights correlated with keylights, and overall reinforcement
      rate changes were carried out. No reliable increase in reinforcement sensitivity
      resulted from any manipulation. Finally, in Experiment 4, reinforcement rates in
      the two components were kept constant and unequal, and the component durations
      were varied. Shorter components produced significantly increased response rates
      normally in the higher reinforcement rate component, but schedule reversals at
      short component durations eliminated the response rate increases. The effects of
      component duration on multiple schedule performance cannot be interpreted as
      changing sensitivity to reinforcement nor to changing bias.

PMID- 16812277
TI  - Incentive processes and the peak shift.
AB  - Intradimensional operant discrimination schedules were employed, which eliminated
      the covariation of response and reinforcement rates that are found on most
      operant baselines. In Phase 1, one keylight (S(1)) controlled an increase in
      pigeons' treadle pressing, relative to another keylight (S(2)), while being
      correlated with a decrease in frequency of reinforcement. In Phase 2 both treadle
      pressing and reinforcement increased in the presence of one keylight, relative to
      the second. In Phase 1 the relatively flat treadle-press generalization gradients
      peaked at S(1), whereas the peaks of those in Phase 2 were shifted from S(1) in a
      direction away from S(2). It was postulated that these positive and negative
      stimulus-reinforcement contingencies influence the likelihood of obtaining peak
      shift through the operation of a classically conditioned "central motive state."
      How response-reinforcement and stimulus-reinforcement contingencies might
      contribute to the development of inhibitory effects of S(2) is discussed.
      Autoshaped key pecking also was produced by these procedures. During
      manipulations of stimuli, the gradients obtained for autoshaped key pecking were
      narrow and sharply peaked at the food-correlated stimulus (S(2)) in Phase 1. This
      failure to obtain peak shift for an elicited response suggests a difference in
      discriminative processes operating in classical and instrumental learning.

PMID- 16812278
TI  - Acquisition and maintenance of postshock response pattern in nondiscriminated
      avoidance with rats.
AB  - Five experimentally naive albino rats were placed under a nondiscriminated lever
      press avoidance schedule in which the delay to the next shock for responses after
      a shock was longer than the delay for responses after a response. Four rats
      acquired the postshock response pattern and maintained it for a prolonged period.
      The results revealed that postshock responding was under operant control and was
      not purely shock-elicited. It was suggested that the two kinds of response-shock
      interval, i.e. the shock-response-shock interval and the response-response-shock
      interval, could and should be independently controlled in nondiscriminated
      avoidance schedules.

PMID- 16812279
TI  - Schedule-induced drinking: Elicitation, anticipation, or behavioral interaction?
AB  - We carried out five experiments with rats on fixed-time schedules in order to
      define the relation between drinking and individual food-pellet presentations. In
      Experiment 1, unsignaled extra food occurred at the end of occasional fixed
      intervals, and we compared subsequent drinking patterns with drinking before the
      extra food presentation. In Experiment 2 we presented signaled and unsignaled
      extra food and measured elicited and anticipatory drinking patterns. In
      Experiment 3, we observed the persistence of modified drinking patterns when
      several consecutive intervals ended with extra pellets. In Experiments 4 and 5,
      we varied the magnitude of food delivery across (rather than within) sessions to
      replicate published findings. Results show that schedule-induced drinking is
      neither elicited by food presentations nor induced by stimuli associated with a
      high food rate. All subjects seemed to follow a simple rule: during any stimulus
      signaling an increase in the local probability of food delivery within a session,
      engage in food-related behavior to the exclusion of drinking. Schedule-induced
      drinking appears to be the result of dynamic interactions among food-related
      behavior, drinking, and other motivated behavior, rather than a direct effect of
      the contingencies of food reinforcement.

PMID- 16812280
TI  - Comparisons between one-key and two-key versions of the sinewave schedule for
      pigeons.
AB  - When the rate of reinforcement for pigeons' key pecking varied over time
      following a sine waveform, performances were more consistent and reliable if a
      constant-rate reinforcement schedule was concurrently available on a second key
      than if only the sinewave-varying reinforcement schedule was available. In the
      two-key version, response rates clearly followed varying reinforcement rates with
      the same frequency, with no phase lag, and without breaks. In both versions,
      pecking rate was a power function of reinforcement rate. Sinewave-schedule
      performance waveforms qualified for engineering methods of frequency analysis and
      met criteria for a standard measurement system.

PMID- 16812281
TI  - The case against Allen's generalization of the matching law.
AB  - Allen (1981) claims to have established the formal validity of a power-function
      generalization of the matching law. This paper argues that Allen's proof is not
      correct when schedules are presented in pairs and that his initial assumptions
      are too restrictive when all schedules are simultaneously available.

PMID- 16812282
TI  - Comment on Houston's arguments.

PMID- 16812283
TI  - Choice, changeover, and travel.
AB  - Since foraging in nature can be viewed as instrumental behavior, choice between
      sources of food, known as "patches," can be viewed as choice between instrumental
      response alternatives. Whereas the travel required to change alternatives deters
      changeover in nature, the changeover delay (COD) usually deters changeover in the
      laboratory. In this experiment, pigeons were exposed to laboratory choice
      situations, concurrent variable-interval schedules, that were standard except for
      the introduction of a travel requirement for changeover. As the travel
      requirement increased, rate of changeover decreased and preference for a favored
      alternative strengthened. When the travel requirement was small, the relations
      between choice and relative reinforcement revealed the usual tendencies toward
      matching and undermatching. When the travel requirement was large, strong
      overmatching occurred. These results, together with those from experiments in
      which changeover was deterred by punishment or a fixed-ratio requirement, deviate
      from the matching law, even when a correction is made for cost of changeover. If
      one accepted an argument that the COD is analogous to travel, the results suggest
      that the norm in choice relations would be overmatching. This overmatching,
      however, might only be the sign of an underlying strategy approximating
      optimization.

PMID- 16812284
TI  - Performance of humans in concurrent avoidance/positive-reinforcement schedules.
AB  - Performance maintained under concurrent schedules consisting of a variable
      interval avoidance component and a variable-interval positive-reinforcement
      component was studied in three human subjects using points exchangeable for money
      as the reinforcer. The rate of responding in the avoidance component increased,
      and the rate of responding in the positive-reinforcement component declined, as a
      function of the frequency of point-losses avoided in the avoidance component. The
      performance of all three subjects conformed to equations proposed by Herrnstein
      to describe behavior in concurrent schedules. The logarithms of the ratios of the
      response rates in the two components, and the logarithms of the ratios of the
      times spent in the two components, were linearly related to the logarithms of the
      ratios of the frequency of loss avoidance in the avoidance component to the
      frequency of reinforcement in the positive-reinforcement component. When a
      changeover delay of 5.0 sec was imposed, the slopes of the linear functions were
      close to 1.0 in the case of two subjects, whereas the third subject exhibited
      significant undermatching. For two subjects the changeover delay was then reduced
      to 2.0 sec; in both cases the slopes of the linear functions were lower than
      under the 5.0-sec condition. One subject participated in a third phase, in which
      no changeover delay was imposed; there was a further reduction in the slopes of
      the linear functions.

PMID- 16812285
TI  - Memory for two stimulus-response items in pigeons.
AB  - Six pigeons served in a discrete-trial experiment on short-term memory.
      Combinations of three key positions and two ordinal positions, yielding six
      possible sequences of stimulus-response pairs, were used as lists of items. A
      retention interval separated list presentation from the test phase in which two
      (for Group 1) or three (for Group 2) keys were illuminated with either red or
      green light. A reinforcer was delivered if a subject pecked the key of the first
      item on a red trial and the key of the second item on a green trial. When the
      retention interval was lengthened from one to five or nine seconds, a systematic
      loss of stimulus control resulted. Lengthening the interval between items from
      one to eight seconds had a much smaller effect for the birds in Group 1, whereas
      a systematic loss of stimulus control was found in red trials for the birds in
      Group 2. The functional relations between choice accuracy and delay provided an
      empirical basis for analysis of what relations among temporal events can become
      discriminative stimuli.

PMID- 16812286
TI  - Memory for recent behavior in the pigeon.
AB  - Variations of the symbolic delayed-matching-to-sample procedure were used to
      study a pigeon's memory for a small number of pecks. In the first experiment a
      choice of a left or right sidekey after a delay or retention interval was
      reinforced if a bird had not pecked at all or had pecked exactly once, before the
      delay, respectively. In the second experiment a choice of a red or green sidekey,
      regardless of its position, was reinforced if a bird had not pecked at all or had
      pecked exactly twice, respectively. In the first experiment a bird could orient
      toward the correct choice during the delay, whereas it could not in the second
      experiment. In a third experiment a feature-probing method was used to study a
      pigeon's memory for a number of pecks in the context of certain other pecks. The
      results showed that a pigeon can remember a small number of pecks for one-half to
      one minute or more and that the percent correct is a decreasing function of the
      log retention interval. When a second number of pecks is different from the first
      number, memory for the first number lasts only a few seconds. When a second
      number is the same, memory lasts considerably longer. The more recent number of
      pecks is remembered better. The results are interpreted in terms of a theory
      which holds that a reinforcer, in general, may act on a subjects' memory for
      recent behavior to generate patterns of behavior.

PMID- 16812287
TI  - Note on aversion learning to the shape of food by monkeys.
AB  - Vervet and grivet monkeys were repeatedly tested eating bar- and circle-shaped
      cookies. One subject was always injected with lithium immediately after eating
      cookies with the circle shape and learned to avoid the circular cookies while
      continuing to eat the bar-shaped cookies. Another subject received similar
      treatment except that lithium injections were always delayed 30 minutes after
      access to the circle-shaped cookies. She also acquired a discriminative aversion.
      Aversion learning was not observed with 60-minute delayed toxicosis or with
      lithium injections administered unpaired with access to the cookies. The two
      types of cookies differed only in shape, and conditioning and test sessions were
      conducted in total darkness to preclude the use of visual cues. Therefore, the
      avoidance observed in subjects conditioned with immediate and 30-minute delayed
      toxicosis represents a conditioned aversion to the shape of the cookies as
      revealed by tactile cues. These findings illustrate that monkeys can learn to
      select food on the basis of tactile stimuli when such stimuli are conditioned
      with delayed aversive stimulation.

PMID- 16812288
TI  - Foraging in a simulated natural environment: There's a rat loose in the lab.
AB  - Rats were required to earn their food in a large room having nine boxes placed in
      it, each of which contained food buried in sand. In different phases of the
      experiment the amount of time allowed for foraging, the amount of food available
      in each food patch, and the location of the different available amounts were
      varied. The rats exhaustively sampled all patches each session but seemed to have
      fairly strong preferences for certain locations over others. If position
      preferences were for patches containing small amounts of food, the sensitivity to
      amount available was increased so that when location was compensated for, a
      pattern of optimal foraging was evident. The importance of environmental
      constraints in producing optimal behavior and the relation of the observed
      behavior to laboratory findings are discussed.

PMID- 16812289
TI  - Editorial.

PMID- 16812290
TI  - Choice and foraging.
AB  - In Experiment 1, six naive pigeons were trained on a foraging schedule
      characterized by different states beginning with a search state in which
      completion of a fixed-interval on a white key led to a choice state. In the
      choice state the subject could, by appropriate responding on a fixed ratio of
      three, either accept or reject the schedule of reinforcement that was offered
      (either a variable-interval five-second or a variable-interval 20-second). If the
      subject accepted the schedule, it entered a "handling state" in which the
      appropriate variable-interval schedule was presented. Completion of the variable
      interval schedule produced food. The independent variable was the fixed-interval
      value in the search state, and the dependent variable was the rate of acceptance
      of the long variable-interval in the choice state. Experiment 2 was identical
      except that the search state required completion of a variable-interval, instead
      of a fixed-interval, schedule. The rate of acceptance of the long variable
      interval schedule in both experiments was a direct function of the length of the
      search state, in accordance with both optimality theory and the delay-reduction
      hypothesis.

PMID- 16812291
TI  - The effects of concurrent responding and reinforcement on behavioral output.
AB  - Four birds key pecked on concurrent variable-interval one-minute variable
      interval four-minute schedules with a two-second changeover delay. Response rates
      to the variable-interval one-minute key were then reduced by signaling its
      reinforcer availability and later by providing its reinforcers independently of
      responding. Each manipulation increased response rates to the variable-interval
      four-minute key even though relative reinforcement rates were unchanged. In a
      final phase, eliminating the variable-interval one-minute key and its schedule
      produced the highest rates of all to the variable-interval four-minute key. These
      results show that both reinforcement and response rates to one schedule influence
      response rates to another schedule. These results join those of Guilkey, Shull, &
      Brownstein (1975) in failing to replicate Catania (1963). Moreover, they violate
      the predictions of the equation for simple action (de Villiers & Herrnstein,
      1976). In terms of a median-rate measure (reciprocal of the median interresponse
      time), rates to the variable-interval four-minute key were high when responding
      was not reduced to the variable-interval one-minute key and were low when it was
      reduced. This rate difference suggests a process difference between concurrent
      schedule procedures that maintain high concurrent response rates versus those
      that do not. This process difference jeopardizes attempts to integrate single-
      and concurrent-operant performances within a single formulation.

PMID- 16812292
TI  - Choice and segmented interreinforcement intervals.
AB  - Pigeons were trained on a two-key concurrent schedule, where food reinforcers on
      one key were arranged by a simple variable-interval schedule and on the other key
      by a chain variable-interval variable-interval schedule. When the initial link of
      the chain was in effect, the pigeons tended to respond more on the simple
      variable-interval schedule, and hence less on the chain, than would be expected
      from a comparison of both the local and overall rates of reinforcement of the two
      schedules. When the terminal link of the chain was in effect, the pigeons
      responded more on the chain than would be expected from a comparison of the rates
      of reinforcement of the schedules then in effect. Overall responding on the chain
      was not proportional to overall reinforcement on the chain but rather was a by
      product of responding during initial- and terminal-link phases.

PMID- 16812293
TI  - Fixed-ratio performance with and without a postreinforcement timeout.
AB  - Pigeons pecked a key, producing food reinforcement on fixed-ratio (FR) schedules
      requiring 50, 100, or 150 responses. In each session, 30-second timeouts were
      inserted before a random half of the FR trials, whereas the other trials began
      immediately after reinforcement. In general, preratio pauses were shorter on
      trials preceded by timeouts. On these trials, the probability of a first response
      tended to be highest in the first 20 seconds of the trials, suggesting that the
      shorter pauses were the result of transient behavioral contrast. Direct
      observations and analyses of interresponse times (IRTs) after the preratio pause
      indicated that IRTs could be grouped into three categories: (1) IRTs of about .1
      second, which were produced by small head movements in the vicinity of the key;
      (2) IRTs of about .3 second, which were produced by distinct pecking motions; and
      (3) IRTs greater than .5 second, which were accompanied by pausing or movements
      away from the key. At all ratio sizes, as a subject progressed through a trial,
      the probability of a long IRT decreased, whereas the probability of an
      intermediate IRT usually increased at first and then decreased. The probability
      of a short IRT increased monotonically across a trial. The results show that
      responding changes systematically as a subject progresses through a ratio on an
      FR schedule. Some characteristics of performance varied as functions of the
      absolute size of the response requirement, whereas others appeared to depend on
      the relative location within a ratio (i.e., the proportion of the ratio completed
      at a given moment).

PMID- 16812294
TI  - Conditional acceleration and external disinhibition of operant lever pressing by
      prereward, neutral, and reinforcing stimuli.
AB  - Rats responding under a differential-reinforcement-of-low-rate schedule increased
      their rates of lever pressing during a 20-second click/flash stimulus that
      preceded the delivery of a response-independent food pellet. The increase could
      not be attributed to suppression of collateral behavior that has been said to
      mediate temporally-spaced responding. We propose that the prereward stimulus
      functioned as an external disinhibitor of lever pressing that had been inhibited
      by the constraints of the operant schedule. Support is derived from the observed
      disinhibitory effects of a 10-second unpaired click/flash stimulus and of
      unsignaled, response-independent pellets that were presented while the animals
      were responding under the same schedule.

PMID- 16812295
TI  - Immediate reinforcement in delayed reward learning in pigeons.
AB  - Pigeons were trained on simultaneous red-green discrimination procedures with
      delayed reward and sequences of stimuli during the delay. In Experiment 1, three
      stimuli appeared during the 60-second intervals between the correct responses and
      reward, and the incorrect responses and nonreward. The stimulus that immediately
      followed a correct response also preceded nonreward, and the stimulus that
      followed an incorrect response preceded reward. These stimuli were 10 or .33
      second in duration for different groups. Stimuli during the remainder of the
      delay interval differed following correct and incorrect responses. Group 10
      initially persisted in the nonrewarded choice, but shifted to a preponderance of
      rewarded responses after further training. Group .33 rapidly acquired the correct
      response. Similar results were obtained in Experiment 2 where delay intervals
      consisted of opposite sequences of two stimuli of equal duration and total delays
      were 6, 20, or 60 seconds. Early in training, generalization of differential
      conditioned-reinforcing properties from the conditions preceding reward and
      nonreward to postchoice conditions had a greater effect relative to backchaining
      than it did later. It was concluded that delayed-reward learning is best analyzed
      in terms of the conditioned-reinforcing value of the patterns of cues that follow
      immediately after rewarded and nonrewarded responses.

PMID- 16812296
TI  - Editor's comment.

PMID- 16812297
TI  - The second offspring of General Process Learning Theory: Overt behavior as the
      ambassador of the mind.
AB  - Wasserman suggested in a recent book review that the study of intervening
      cognitive processes represents a current focus of interest in animal learning and
      that this has led to a revitalization of comparative psychology. An examination
      of the volume reviewed suggests that he may have overstated the case. Most of the
      authors to whom he refers expressed dissatisfaction with traditional stimulus
      response associationism but few argued for the extreme (information processing)
      sort of cognitive approach described by Wasserman.

PMID- 16812298
TI  - Further remarks on the role of cognition in the comparative analysis of behavior.
AB  - Recent interest in comparative psychology has stimulated much research and debate
      concerning cognitive processes in animal behavior. The present paper relates to
      this general area by treating particular issues in the analysis of comparative
      cognition: specifically, how cognition is inferred from animal behavior; whether
      the postulation of intervening cognitive processes furthers our understanding of
      behavior; and how rival approaches help advance the science of behavior.

PMID- 16812299
TI  - Incentive theory: II. Models for choice.
AB  - Incentive theory is extended to account for concurrent chained schedules of
      reinforcement. The basic model consists of additive contributions from the
      primary and secondary effects of reinforcers, which serve to direct the behavior
      activated by reinforcement. The activation is proportional to the rate of
      reinforcement and interacts multiplicatively with the directive effects. The two
      free parameters are q, the slope of the delay of reinforcement gradient, whose
      value is constant across many experiments, and b, a bias parameter. The model is
      shown to provide an excellent description of all results from studies that have
      varied the terminal-link schedules, and of many of the results from studies that
      have varied initial-link schedules. The model is extended to diverse
      modifications of the terminal links, such as varied amount of reinforcement,
      varied signaling of the terminal-link schedules, and segmentation of the terminal
      link schedules. It is demonstrated that incentive theory provides an accurate and
      integrated account of many of the phenomena of choice.

PMID- 16812300
TI  - Instructed versus shaped human verbal behavior: Interactions with nonverbal
      responding.
AB  - Undergraduate students' presses on left and right buttons occasionally made
      available points exchangeable for money. Blue lights over the buttons were
      correlated with multiple random-ratio random-interval components; usually, the
      random-ratio schedule was assigned to the left button and the random-interval to
      the right. During interruptions on the multiple schedule, students filled out
      sentence-completion guess sheets (e.g., The way to earn points with the left
      button is to...). For different groups, guesses were shaped with differential
      points also worth money (e.g., successive approximations to "press fast" for the
      left button), or were instructed (e.g., Write "press slowly" for the left
      button), or were simply collected. Control of rate of pressing by guesses was
      examined in individual cases by reversing shaped or instructed guesses, by
      instructing pressing rates, and/or by reversing multiple-schedule contingencies.
      Shaped guesses produced guess-consistent pressing even when guessed rates opposed
      those characteristic of the contingencies (e.g., slow random-ratio and fast
      random-interval rates), whereas guesses and rates of pressing rarely corresponded
      after unsuccessful shaping of guesses or when guessing had no differential
      consequences. Instructed guesses and pressing were inconsistently related. In
      other words, when verbal responses were shaped (contingency-governed), they
      controlled nonverbal responding. When they were instructed (rule-governed), their
      control of nonverbal responding was inconsistent: the verbal behavior sometimes
      controlled, sometimes was controlled by, and sometimes was independent of the
      nonverbal behavior.

PMID- 16812301
TI  - Topography of signal-centered behavior in the rat: Effects of deprivation state
      and reinforcer type.
AB  - In a series of three experiments, groups of food-deprived and water-deprived rats
      were given pairings of a retractable lever (CS(+)) with response-independent
      deliveries of either solid or liquid reinforcers. In Experiment 1 food-deprived
      rats given a solid-pellet reinforcer differentially tended to sniff, paw, mouth,
      and bite the CS(+) lever more often than a lever that was not paired with food
      (CS(-)), whereas food-deprived rats given a liquid reinforcer tended to
      differentially sniff, paw, and lick the CS(+) lever. 23(1/2)-hour water-deprived
      rats given liquid reinforcers showed very little CS(+) contact. In Experiment 2
      increasing the severity of water deprivation from 23(1/2) to 47(1/2) hours
      significantly increased CS(+) contact. In Experiment 3, subjects that were
      simultaneously food and water deprived and given a water reinforcer failed to
      exhibit differential CS(+) contact, but subjects that were simultaneously food
      and water deprived and given a food reinforcer did acquire differential CS(+)
      contact behavior. These results suggest that (a) even under a single motivational
      state the nature of signal-centered behavior can be determined by type of
      reinforcer, (b) although water reinforcement produces less signal contact than
      food reinforcement, this can be facilitated with more severe water-deprivation
      levels, and (c) high CS-contact rates using food reinforcement are not simply a
      product of reductions in body weight with food deprivation.

PMID- 16812302
TI  - Choice, relative reinforcer duration, and the changeover ratio.
AB  - Relative reinforcer duration was varied in concurrent schedules with a fixed
      ratio four changeover requirement. The schedule in effect after each reinforcer
      was randomly chosen. For all three pigeons, relative response rates overmatched
      relative reinforcer durations. Time allocation was less extreme and, on the
      average, matched relative reinforcer duration. In a subsequent manipulation, the
      level of preference was shown to depend on the size of the changeover
      requirement. These results are similar to those from related unequal
      reinforcement-frequency procedures.

PMID- 16812303
TI  - Choice and the relative immediacy of reinforcement.
AB  - The relative immediacy of reinforcement in concurrent-chain schedules was varied
      while the relative reduction in the overall average time to reinforcement
      associated with terminal-link entry was held constant. For each of four pigeons,
      choice did not vary with relative immediacy of reinforcement. Subsequently,
      choice by the same subjects was shown to be sensitive to relative reduction in
      average time to reinforcement.

PMID- 16812304
TI  - An invariant relation between changing over and reinforcement.
AB  - Although concurrent schedules may arrange reinforcers irregularly, relatively
      large numbers of reinforcers are obtained when an animal changes from one
      schedule to the other. This paper proposes a quantitative relation that predicts
      the proportion of reinforcers obtained when an animal is working on a schedule
      and the proportion when the animal changes over to a schedule. Basically the
      relation states that the number of reinforcers obtained while an animal works on
      a schedule varies directly with the relative amount of time spent working on that
      schedule; and the number of reinforcers obtained when an animal changes to a
      schedule varies directly with the relative amount of time spent on the alternate
      schedule. An important aspect of this relation is that when relative
      reinforcement rates are less than .50, more reinforcers are obtained just after
      an animal changes to a schedule than at all other times when this schedule is
      engaged. Data obtained both from a stat-bird and a live pigeon were in close
      agreement with the quantitative predictions. The relation between changing over
      and reinforcement held across several procedural changes that included changes in
      relative reinforcement rate, changes from independent to interdependent
      scheduling procedures, and changes in the variable-interval reinforcement
      distributions. The results are discussed in terms of the effects of the local
      distribution of reinforcement on responding. The local reinforcement distribution
      can affect local response rates and affects the resulting matching relation. This
      arrangement has implications for explanations of choice.

PMID- 16812305
TI  - Free-operant forgetting: Delayed stimulus control of multiple-schedule
      performance.
AB  - Pigeons' responses were reinforced in two components of several multiple variable
      interval variable-interval schedules of food reinforcement. In one component, the
      key was illuminated green for 15 seconds and white for 45 seconds. In the other
      component, the key was illuminated red for 15 seconds and white for 45 seconds.
      Values for the exponent of the power functions relating response ratios to
      reinforcement ratios were higher in the presence of the discriminative stimuli
      (green or red) than in the presence of white. Sensitivity of response ratios to
      changes in reinforcement ratios provided an index of the extent to which
      responding was under delayed stimulus control by prior discriminative stimuli.

PMID- 16812306
TI  - Dynamic effects of food magnitude on interim-terminal interaction.
AB  - We tested the assumption of a facilitatory relation between periodic food
      presentation and schedule-induced drinking by examination of (a) elicited
      drinking, (b) drinking in anticipation of food delivery, and (c) possible
      indirect effects of food delivery on drinking. We exposed rats to a fixed-time 60
      second schedule in which interfood intervals ended in either one or four food
      pellets with equal probability. In Phases 1 and 3, a stimulus signaled the
      magnitude of upcoming food presentation. In Phase 2, the stimulus was eliminated.
      Changes in drinking and "head-in-feeder" distributions within interfood intervals
      demonstrated that head-in-feeder was controlled directly by food presentation,
      but drinking was not. Head-in-feeder increased and drinking was reduced when
      large meals began or ended an interval. In Phases 4 to 6, meal size was
      manipulated across sessions yielding a positive relation between meal size and
      schedule-induced drinking. We conclude: (1) Schedule-induced drinking is
      determined by distributions of food-related behavior and results from indirect
      effects of food delivery; and (2) the amount of schedule-induced drinking and the
      form of the drinking distributions in this experiment can be accurately explained
      by two assumptions: (a) Food presentation facilitates food-related behavior
      through elicitation and anticipation; and (b) food-related behavior and drinking
      are reciprocally, linearly related.

PMID- 16812308
TI  - Digital filters in behavioral research.

PMID- 16812307
TI  - Positive behavioral contrast when pigeons press treadles during multiple
      schedules.
AB  - Pigeons were placed on multiple variable-interval 15-second variable-interval 15
      second and on multiple variable-interval 15-second extinction schedules in which
      treadle presses produced food reinforcers. Positive behavioral contrast occurred.
      That is, rates of responding were higher during the variable-interval 15-second
      component when the other component was extinction than when it was another
      variable-interval 15-second schedule. These results contradict the findings of
      other studies, which failed to find positive contrast when pigeons pressed
      treadles for food reinforcers. They may also question the additive theories of
      behavioral contrast that predict that contrast should not occur in this
      situation.

PMID- 16812309
TI  - Sensitivity to reinforcement in concurrent arithmetic and exponential schedules.
AB  - The generalized matching law states that the logarithm of the ratio of responses
      emitted or time spent responding in concurrent variable-interval schedules is a
      linear function of the logarithm of the ratio of reinforcements obtained. The
      slope of this relation, sensitivity to reinforcement, varies about 1.0 but has
      been shown to be different when obtained in different laboratories. The present
      paper analyzed the results from 18 experiments on concurrent variable-interval
      schedule performance and showed that response-allocation sensitivity to
      reinforcement was significantly smaller when arithmetic, rather than exponential,
      progressions were used to produce variable-interval schedules. There were no
      differences in time-allocation sensitivity between the two methods of
      constructing variable-interval schedules. Since the two laboratories have
      consistently used different methods for constructing variable-interval schedules,
      the differences in obtained sensitivities to reinforcement are explained. The
      reanalysis suggests that animals may be sensitive to differences in the
      distribution of reinforcements in time.

PMID- 16812311
TI  - Don hake, behavior analyst: a memorial.

PMID- 16812310
TI  - Hill-climbing by pigeons.
AB  - Pigeons were exposed to two types of concurrent operant-reinforcement schedules
      in order to determine what choice rules determine behavior on these schedules. In
      the first set of experiments, concurrent variable-interval, variable-interval
      schedules, key-peck responses to either of two alternative schedules produced
      food reinforcement after a random time interval. The frequency of food
      reinforcement availability for the two schedules was varied over different ranges
      for different birds. In the second series of experiments, concurrent variable
      ratio, variable-interval schedules, key-peck responses to one schedule produced
      food reinforcement after a random time interval, whereas food reinforcement
      occurred for an alternative schedule only after a random number of responses.
      Results from both experiments showed that pigeons consistently follow a
      behavioral strategy in which the alternative schedule chosen at any time is the
      one which offers the highest momentary reinforcement probability (momentary
      maximizing). The quality of momentary maximizing was somewhat higher and more
      consistent when both alternative reinforcement schedules were time-based than
      when one schedule was time-based and the alternative response-count based.
      Previous attempts to provide evidence for the existence of momentary maximizing
      were shown to be based upon faulty assumptions about the behavior implied by
      momentary maximizing and resultant inappropriate measures of behavior.

PMID- 16812312
TI  - The analysis of behavioral momentum.
AB  - Learned behavior varies in its resistance to change, depending on the rate of
      reinforcement. Resistance to change may be characterized as behavioral momentum,
      which in turn may be analyzed into terms corresponding to mass and velocity in
      classical physics. Behavioral mass may be inferred from changes in response rate
      when experimental conditions are altered. Relevant data were obtained by training
      pigeons to peck a key on two-component multiple variable-interval, variable
      interval schedules. Six pigeons were studied on three pairs of variable-interval
      schedules in all possible orders. When performance stabilized, resistance to
      change was assessed by arranging response-independent food during periods between
      components and by extinction. For each operation, the data for all schedule
      performances converged onto a single function, permitting estimation of the ratio
      of behavioral masses for each pair of schedules. The response-independent food
      data suggested that the ratio of behavioral masses is a power function of the
      ratio of reinforcement rates and that behavioral mass may be measured on a ratio
      scale.

PMID- 16812313
TI  - Analysis of discriminative control by social behavioral stimuli.
AB  - Visual discriminative control of the behavior of one rat by the behavior of
      another was studied in a two-compartment chamber. Each rat's compartment had a
      food cup and two response keys arranged vertically next to the clear partition
      that separated the two rats. Illumination of the leader's key lights signaled a
      "search" period when a response by the leader on the unsignaled and randomly
      selected correct key for that trial illuminated the follower's keys. Then, a
      response by the follower on the corresponding key was reinforced, or a response
      on the incorrect key terminated the trial without reinforcement. Accuracy of
      following the leader increased to 85% within 15 sessions. Blocking the view of
      the leader reduced accuracy but not to chance levels. Apparent control by visual
      behavioral stimuli was also affected by auditory stimuli and a correction
      procedure. When white noise eliminated auditory cues, social learning was not
      acquired as fast nor as completely. A reductionistic position holds that
      behavioral stimuli are the same as nonsocial stimuli; however, that does not mean
      that they do not require any separate treatment. Behavioral stimuli are usually
      more variable than nonsocial stimuli, and further study is required to
      disentangle behavioral and nonsocial contributions to the stimulus control of
      social interactions.

PMID- 16812314
TI  - Sample-specific ratio effects in matching to sample.
AB  - In a symbolic matching-to-sample task, pigeons were trained using sample
      specific, fixed-ratio "observing responses." Subsequently, in a mixed condition,
      each sample was presented equally often with each ratio requirement, i.e., the
      ratios were no longer correlated with the samples. In a second experiment,
      pigeons were trained initially in the mixed condition and subsequently shifted to
      the sample-specific condition in which the required ratios were correlated with
      the samples. Results of both experiments suggested joint control of choices by
      ratio value and by the exteroceptive stimuli. The discriminative properties of
      the ratios appeared to outweigh absolute ratio-size effects.

PMID- 16812315
TI  - Reinforcement of inhibition.
AB  - A differential-reinforcement-of-other-behavior (DRO) schedule with trials and
      delayed reinforcement was investigated. Periodically a wheel was briefly
      available to rats, followed six seconds later by brief availability of a bar.
      Variable-ratio food reinforcement of wheel turns was adjusted to give 95% turns.
      After variable-ratio-five reinforcement of bar presses produced 100% pressing,
      then separate ratio schedules were used for presses following turns (turn
      presses) and presses following nonturns (nonturn presses). Increasing nonturn
      press reinforcements decreased turns, even though total reinforcements increased.
      Reversal by decreasing nonturn-press reinforcements raised turns, though with
      hysteresis. Thus food reinforcement increased nonturns even though delayed six to
      ten seconds after nonturns, a delay that greatly reduces response reinforcement.
      Those and other results indicate that the turn decrease was not due to
      reinforcement of competing responses. Evidence against other alternatives, and
      the reduction of responding by increased reinforcement, indicate that the term
      inhibition is appropriate for the phenomenon reinforced. Response-specific
      inhibition appears appropriate for this particular kind, since its effects are
      more specific to particular responses than Pavlovian conditioned-inhibition.
      Response-specific inhibition seems best considered a behavioral output comparable
      to responses (e.g., both reinforcible) but with important properties different
      from responses (e.g., different reinforcement-delay gradients).

PMID- 16812316
TI  - Spatial and temporal relations in conditioned reinforcement and observing
      behavior.
AB  - In Experiment 1, depressing one perch produced stimuli indicating which of two
      keys, if pecked, could produce food (spatial information) and depressing the
      other perch produced stimuli indicating whether a variable-interval or an
      extinction schedule was operating (temporal information). The pigeons increased
      the time they spent depressing the perch that produced the temporal information
      but did not increase the time they spent depressing the perch that produced the
      spatial information. In Experiment 2, pigeons that were allowed to produce
      combined spatial and temporal information did not acquire the perch pressing any
      faster or maintain it at a higher level than pigeons allowed to produce only
      temporal information. Later, when perching produced only spatial information, the
      time spent depressing the perch eventually declined. The results are not those
      implied by the statement that information concerning biologically important
      events is reinforcing but are consistent with an interpretation in terms of the
      acquisition of reinforcing properties by a stimulus associated with a higher
      density of primary reinforcement.

PMID- 16812317
TI  - Autoshaped responding: A baseline for studying stimulus preference.
AB  - In an autoshaping procedure with pigeons, trials consisted of the illumination of
      two keys, each with a different color, and then a response-independent feeder
      operation. Over successive conditions, all key-color pairs were arranged from the
      set of amber, red, green, and blue lamps. During sessions with a given pair, the
      left-right configuration of the colors varied irregularly, and the two colors
      alternated in illuminating the feeder. With one red and one green key, for
      example, red appeared sometimes on the left and sometimes on the right, and the
      feeder was alternately lit red or green on successive trials. Both total pecks
      and proportion of trials with at least one peck on a key of a given color were
      generally greater for red and amber than for green and blue, and relations among
      preferences were generally transitive across different color pairs. Repeating the
      procedure with decreased red and amber intensities and increased green and blue
      intensities reduced red and amber pecking relative to green and blue pecking,
      implying that differences in responding were determined more strongly by
      intensive than by chromatic properties of the stimuli.

PMID- 16812318
TI  - Preference for mixed versus constant delays of reinforcement: Effect of
      probability of the short, mixed delay.
AB  - Preference for mixed versus constant delays of reinforcement was studied with a
      concurrent-chain procedure. Lever pressing by rats in concurrently available
      variable-interval 60-second initial links occasionally produced mutually
      exclusive terminal-link reinforcement delays. A constant delay of reinforcement
      (either 15 seconds or 30 seconds) composed one terminal link and mixed delays (.2
      second and twice the value of the constant delay) were arranged in the other
      terminal link. The proportion of .2-second delays in the mixed-delay terminal
      link took on values of 0, .1, .25, .5, .75, .9, and 1.0 over experimental
      conditions. Based on relative rates of responding in the initial links,
      preference for the mixed delays was a negatively accelerated function of the
      proportion of short, mixed delays. Three of five rats preferred the mixed delays
      to the constant delays when the proportion of short, mixed delays was .1 or
      higher, and all five rats preferred the mixed delays when the proportion of
      short, mixed delays was .25 or higher. Neither Squires and Fantino's (1971) delay
      reduction model of choice nor a model based on the harmonic mean reinforcement
      delay provided a close estimate of choice proportions over the range of short
      delay proportions studied. The delay-reduction model underestimated choice for
      the mixed delays at low and intermediate proportions of short delays, and the
      harmonic-mean-delay model overestimated choice for the mixed delays at
      intermediate and high proportions of short delays.

PMID- 16812319
TI  - Response rate, latency, and resistance to change.
AB  - Pigeons were trained on a multiple variable-interval/variable-interval schedule
      with pacing contingencies that generated high response rates in one component and
      low response rates in the other. Timeout periods separated the schedule
      components. During resistance-to-change tests, response-independent food was
      presented during the timeout periods, and the duration of that food presentation
      was varied among test sessions. Response rates in the schedule components
      decreased and latencies to the first response increased as a function of the
      duration of food presentations during the timeout. Both dependent measures
      changed about the same amount relative to their own baseline levels. The
      conclusions are that baseline response rates controlled by pacing contingencies
      are equally resistant to change, given equal reinforcement densities, and latency
      is a sensitive measure of resistance to change.

PMID- 16812320
TI  - Choice between response units: The rate constancy model.
AB  - In a conjoint schedule, reinforcement is available simultaneously on two or more
      schedules for the same response. The present experiments provided food for key
      pecking on both a random-interval and a differential-reinforcement-of-low-rate
      (DRL) schedule. Experiment 1 involved ordinary DRL schedules; Experiment 2 added
      an external stimulus to indicate when the required interresponse time had
      elapsed. In both experiments, the potential reinforcer frequency from each
      component was varied by means of a second-order fixed-ratio schedule, and the DRL
      time parameter was changed as well. Response rates were described by a model
      stating that time allocation to each component matches the relative frequency of
      reinforcement for that component. When spending time in a given component, the
      subject is assumed to respond at the rate characteristic of baseline performance.
      This model appeared preferable to the absolute-rate version of the matching law.
      The model was shown to be applicable to multiple-response concurrent schedules as
      well as to conjoint schedules, and it described some of the necessary conditions
      for response matching, undermatching, and bias. In addition, the pigeons did not
      optimize reinforcer frequency.

PMID- 16812321
TI  - Steady-state performance on fixed-, mixed-, and random-ratio schedules.
AB  - Three groups of rats pressed a lever for milk reinforcers on various simple
      reinforcement schedules (one schedule per condition). In Group M, each pair of
      conditions included a mixed-ratio schedule and a fixed-ratio schedule with equal
      average response:reinforcer ratios. On mixed-ratio schedules, reinforcement
      occurred with equal probability after a small or a large response requirement was
      met. In Group R, fixed-ratio and random-ratio schedules were compared in each
      pair of conditions. For all subjects in these two groups, the frequency
      distributions of interresponse times of less than one second were very similar on
      all ratio schedules, exhibiting a peak at about .2 seconds. For comparison,
      subjects in Group V responded on variable-interval schedules, and few
      interresponse times as short as .2 seconds were recorded. The results suggest
      that the rate of continuous responding is the same on all ratio schedules, and
      what varies among ratio schedules is the frequency, location, and duration of
      pauses. Preratio pauses were longer on fixed-ratio schedules than on mixed-ratio
      or random-ratio schedules, but there was more within-ratio pausing on mixed-ratio
      and random-ratio schedules. Across a single trial, the probability of an
      interruption in responding decreased on fixed-ratio schedules, was roughly
      constant on random-ratio schedules, and often increased and then decreased on
      mixed-ratio schedules. These response patterns provided partial support for
      Mazur's (1982) theory that the probability of instrumental responding is directly
      related to the probability of reinforcement and the proximity of reinforcement.

PMID- 16812322
TI  - Behavior induced by periodic food delivery: The effects of interfood interval.
AB  - Pigeons were exposed to fixed-time schedules of food presentation ranging from
      five to 300 seconds. Although consistent, stereotyped response patterns developed
      during interfood intervals on all schedules, there were distinct differences in
      the behavior observed on schedules with short, as opposed to long, intervals.
      During the shorter intervals, responses were performed quite vigorously, a feeder
      directed terminal response was observed, and most activities were localized near
      the feeder. On the longer schedules, no feeder-directed terminal response
      developed, although the birds were usually near the feeder at the end of
      intervals. The predominant response involved moving about the chamber, often
      pacing along one of the walls. Performance during short intervals is accounted
      for quite well by the antagonistic-motivational state hypothesis suggested by
      Staddon (1977); however, performance during longer intervals is not. Behavior
      during interfood intervals may more accurately be classified as reflecting a
      single (food) motivational state and described simply in terms of Craig's (1918)
      appetitive behavior.

PMID- 16812323
TI  - Fixed-interval performance: The dynamics of behavior and the interval length.
AB  - Postreinforcement pauses from successive intervals under various fixed-interval
      schedules (ranging from 15 seconds to 480 seconds in length) were subjected to
      lag-1 autocorrelation analysis. Results from both rats and pigeons suggested that
      there was a consistent tendency for pause values in successive intervals to be
      weakly positively related. This tendency did not appear to change systematically
      with interval length and was exhibited both when the reinforcer magnitude was
      constant and when it was variable at different interval values. The findings do
      not support suggestions that the dynamic properties of performance under fixed
      interval schedules vary systematically with interval length, and are in the
      opposite direction from some previous findings suggesting that measures of
      behavior (such as post-reinforcement pause length or number of responses) in
      successive intervals are inversely related.

PMID- 16812324
TI  - The microanalysis of fixed-interval responding.
AB  - The fixed-interval schedule of reinforcement is one of the more widely studied
      schedules in the experimental analysis of behavior and is also a common baseline
      for behavior pharmacology. Despite many intensive studies, the controlling
      variables and the pattern of behavior engendered are not well understood. The
      present study examined the microstructure and superstructure of the behavior
      engendered by a fixed-interval 5- and a fixed-interval 15-minute schedule of food
      reinforcement in the pigeon. Analysis of performance typical of fixed-interval
      responding indicated that the scalloped pattern does not result from smooth
      acceleration in responding, but, rather, from renewed pausing early in the
      interval. Individual interresponse-time (IRT) analyses provided no evidence of
      acceleration. There was a strong indication of alternation in shorter-longer
      IRTs, but these shorter-longer IRTs did not occur at random, reflecting instead a
      sequential dependency in successive IRTs. Furthermore, early in the interval
      there was a high relative frequency of short IRTs. Such a pattern of early pauses
      and short IRTs does not suggest behavior typical of reinforced responding as
      exemplified by the pattern found near the end of the interval. Thus, behavior
      from clearly scalloped performance can be classified into three states:
      postreinforcement pause, interim behavior, and terminal behavior.

PMID- 16812325
TI  - Another look at contrast in multiple schedules.
AB  - Recent research on multiple schedule interactions is reviewed. Contrary to
      formulations that view contrast as the result of elicited behavior controlled by
      the stimulus-reinforcer contingency (e.g., additivity theory), the major
      controlling variable is the relative rate of reinforcement, which cannot be
      reduced to some combination of stimulus-reinforcer and response-reinforcer
      effects. Other recent theoretical formulations are also reviewed and all are
      found to face serious counterevidence. The best description of the available data
      continues to be in terms of the "context of reinforcement," but Herrnstein's
      (1970) formulation of the basis of such context effects appears to be inadequate.
      An alternative conception is provided by Catania's concept of "inhibition by
      reinforcement," by which rate of responding is inversely related to the average
      rate of reinforcement in the situation. Such a conception is related to Gibbon's
      recent scalar-expectancy account of autoshaping and Fantino's delay-reduction
      model of conditioned reinforcement, suggesting that a common set of principles
      determines several diverse conditioning phenomena. However, the empirical status
      of such a description remains uncertain, because recent evidence shows that
      schedule interactions are temporally asymmetric, depending primarily upon the
      conditions of reinforcement that follow a schedule component.

PMID- 16812326
TI  - Eating and drinking: An economic analysis.
AB  - Food-deprived rats were exposed to various schedules of food delivery; water
      deprived rats were exposed to various schedules of water delivery. Eating and
      drinking were measured over sessions and at points throughout sessions. The
      symmetries and asymmetries of food and water consumption were explored in terms
      of: (1) substitutability of food versus water, and of food and water on the one
      hand versus leisure on the other, (2) constraints imposed by various schedules of
      food and water, and (3) the tendency of rats to maximize utility within the
      imposed constraints.

PMID- 16812327
TI  - Temporal constraint on choice: Sensitivity and bias in multiple schedules.
AB  - In multiple schedules of reinforcement, ratios of responses in successive
      components are relatively insensitive to ratios of obtained reinforcers. An
      analysis is proposed that attributes changes in absolute response rates to
      concurrent interactions between programmed reinforcement and extraneous
      reinforcement in other components. The analysis predicts that ratios of responses
      in successive components vary with reinforcer ratios, qualified by a term
      describing the reinforcement context, that is, programmed and extraneous
      reinforcers. Two main predictions from the analysis were confirmed in an
      experiment in which pigeons' responses were reinforced in the components of a
      multiple schedule and analog extraneous reinforcement was scheduled for an
      alternative response in each component. Sensitivity of response and time ratios
      to reinforcer ratios in the multiple schedules varied as a function of the rate
      of extraneous reinforcers. Bias towards responding in one component of the
      multiple schedule varied as an inverse function of the ratios of extraneous
      reinforcer rate in the two components. The data from this and previous studies of
      multiple-concurrent performance were accurately predicted by our analysis and
      supported our contention that the allocation of behavior in multiple-schedule
      components depends on the relative values of concurrently-available reinforcers
      within each component.

PMID- 16812328
TI  - Delay and amount of reward in a concurrent chain.
AB  - Eight pigeons responded under a concurrent-chain schedule for rewards differing
      in both delay and amount, the larger reward being associated with the longer
      delay. Preference was examined as the absolute durations of the terminal-link
      delays were increased at four different delay ratios. Difficulties with other
      experiments of this type were controlled for by the use of (a) a single-tape
      initial link to equalize terminal-link entries, (b) a blackout following the more
      immediate reward to equalize terminal-link length, and (c) a photocell to measure
      reinforcer duration more accurately. Preference for the larger reward changed
      systematically as delays increased in all conditions, decreasing for the 6:1,
      3:1, and 3:2 ratios, and increasing for the 1:1 ratio. These results were similar
      to, but significantly different from, those of previous investigations. The
      implications of these results for various models of concurrent-chain behavior are
      discussed.

PMID- 16812329
TI  - Ratio responding as a function of concurrent avoidance schedules, yoked shocks,
      and ratio value.
AB  - Fixed-ratio food-reinforced responding in rats was studied alone and with
      concurrent shock avoidance or with concurrent response-independent shocks matched
      to those that occurred in the avoidance condition. Under each condition, fixed
      ratio size was increased over successive daily sessions. Fixed-ratio response
      rate generally passed through a maximum as a function of fixed-ratio size.
      Decreased fixed-ratio responding at values beyond the maximum occurred when (1)
      the time to complete a fixed ratio approximated the response-shock interval of
      the avoidance schedule, (2) the shock rate increased, and/or (3) the ratio
      requirements were so high that ratio strain occurred. Avoidance rates decreased
      slightly as fixed-ratio size increased.

PMID- 16812330
TI  - Quantification of rats' behavior during reinforcement periods.
AB  - What is treated as a single unit of reinforcement often involves what could be
      called a reinforcement period during which two or more acts of ingestion may
      occur, and each of these may have associated with it a series of responses, some
      reflexive, some learned, that lead up to ingestion. Food-tray presentation to a
      pigeon is an example of such a "reinforcement period." In order to quantify this
      behavior, a continuous-reinforcement schedule was used as the reinforcement
      period and was chained to a fixed-ratio schedule. Both fixed-ratio size and
      reinforcement-period duration were manipulated. Rats were used as subjects, food
      as reinforcement, and a lever press as the operant. Major findings included (a) a
      rapid decline in response rates during the first 15 to 20 seconds of the
      reinforcement periods, and (b) a strong positive relationship between these
      response rates and the size of the fixed ratio. Also revealed was a short scallop
      not normally found in fixed-ratio response patterns, whose length was a function
      of fixed-ratio size and reinforcement-period duration. It is suggested that
      rapidly fluctuating excitatory processes can account for many of these findings
      and that such processes are functionally significant in terms of behavioral
      compensation.

PMID- 16812331
TI  - Temporal control in a complex environment: An analysis of schedule-related
      behavior.
AB  - Three experiments conducted in an automated ten-compartment chamber recorded
      collateral activities of rats reinforced for lever pressing on differential
      reinforcement-of-low-rate schedules. In Experiment 1, the rate of lever pressing
      increased when stimulus support for collateral activities was removed, thus
      confirming earlier findings. However, there were no temporal or sequential
      patterns of collateral activities that predicted operant responding. In
      Experiment 2, the rate of lever pressing increased only if (a) access to all
      stimulus support for collateral activities was simultaneously prevented, and (b)
      the rat was forced to remain in the presence of the lever and food tray. The
      availability of any of the stimuli related to collateral activity was sufficient
      to keep lever-pressing rates from increasing. Experiment 3 examined collateral
      activities under a signaled differential-reinforcement-of-low-rate schedule.
      Preventing access to stimuli supporting collateral activities had little effect
      on stable lever pressing when the signal was maintained. When the signal was
      removed, collateral activities continued, but lever-pressing rates increased in
      three of the four rats and rates of food presentation declined in all rats.
      Hypotheses that collateral activities have (a) a timekeeping or discriminative
      function, or (b) directly inhibit operant responding were not supported. The
      results suggest that collateral activities may facilitate operant responding by
      simply removing the subject from the presence of reinforcement-related stimuli.

PMID- 16812332
TI  - Matching, statistics, and common sense.

PMID- 16812333
TI  - Choice: Some quantitative relations.
AB  - Six pigeons responded in fifty-six conditions on a concurrent-chains procedure.
      Conditions included several with equal initial links and unequal terminal links,
      several with unequal initial links and equal terminal links, and several with
      both unequal initial and terminal links. Although the delay-reduction hypothesis
      accounted well for choice when the initial links were equal (mean deviation of
      .04), it fit the data poorly when the initial links were unequal (mean deviation
      of .18). A modification of the delay-reduction hypothesis, replacing the rates of
      reinforcement with the square roots of these rates, fit the data better than
      either the unmodified delay-reduction equation or Killeen's (1982) model. The
      modified delay-reduction equation was also consistent with data from prior
      studies using concurrent chains. The absolute rates of responding in each
      terminal link were well described by the same hyperbola (Herrnstein, 1970) that
      describes response rates on simple interval schedules.

PMID- 16812334
TI  - Bias and sensitivity to reinforcement in a concurrent-chain schedule.
AB  - Six pigeons were trained on concurrent-chain schedules in which the initial links
      were either dependent (Experiment 1) or independent (Experiment 2) concurrent
      variable-interval schedules and the terminal links were fixed-duration delays to
      reinforcement in blackout. A changeover delay of three seconds operated in the
      initial links. Both the initial- and terminal-link schedule values were varied
      over 61 experimental conditions. An analysis of the data using the generalized
      matching law showed that the sensitivity of initial-link response allocation to
      the frequency of terminal-link production was independent of both the duration of
      the terminal-link delays and, though less clearly, of the duration of the initial
      link schedules. Sensitivity of initial-link response allocation to terminal-link
      reinforcer-rate ratios was a joint function of the terminal-link durations and
      the smaller average initial-link duration. The results showed that the
      generalized matching law is useful in analyzing concurrent-chain schedule
      performance and that a changeover delay in the initial links eliminates some
      terminal- to initial-link interactions that have made quantitative predictions
      for concurrent-chain performances difficult.

PMID- 16812335
TI  - Concurrent schedules: Spatial separation of response alternatives.
AB  - Four pigeons were exposed to independent concurrent variable-interval 20-second
      variable-interval 60-second schedules of reinforcement. A transparent partition
      was inserted midway between the two response keys. The length of the partition
      was systematically manipulated. Increasing partition length produced a decrease
      in changeover rate in Experiment 1. Over-matching was observed with a partition
      length of 20 centimeters. In Experiment 2 a four-second limited hold was added to
      the schedules. Increasing partition length produced a decrease in changeover rate
      that exceeded the decrease observed in Experiment 1. This manipulation produced
      nearly exclusive choice of the variable-interval 20-second component. The present
      results, together with results obtained in related research, suggest that
      deviation from matching is a function of procedural variables that determine the
      consequences of a changeover response.

PMID- 16812336
TI  - Autoshaping in the rat: The effects of localizable visual and auditory signals
      for food.
AB  - Two experiments investigated autoshaping in rats to localizable visual and
      auditory conditioned stimuli predicting response-independent food. In Experiment
      1 considerable conditioned-stimulus approach behavior was generated by a
      localizable visual conditioned stimulus that was situated approximately 35 cm
      from the food tray. Using the same apparatus in Experiment 2 we found that the
      conditioned-stimulus approach was generated only to a visual conditioned stimulus
      and not to a localizable auditory conditioned stimulus even though subjects (1)
      could discriminate presentations of the auditory conditioned stimulus, (2) had
      associated it with food, (3) could localize it, and (4) would approach the
      auditory stimulus if this behavior constituted an instrumental response to food.
      The predominant conditioned responses to the auditory stimuli were goal tracking
      (entering the food tray) and orienting towards the food-paired conditioned
      stimulus by head turning and rearing and turning. These results imply that rats
      do not invariably approach a localizable appetitive Pavlovian conditioned
      stimulus but that stimulus-approach responses depend on the nature and modality
      of the conditioned stimulus.

PMID- 16812337
TI  - Duration-reduction of avoidance sessions as negative reinforcement.
AB  - Five rats were exposed to a shock-postponement procedure in which responses on
      each of two levers initially had equivalent effects. After an initial training
      sequence that ensured at least some responding on each lever, an additional
      consequence was made conjointly operative on the previously less-preferred lever
      for each animal. Each response on this lever continued to postpone shock, but
      also reduced the session duration by one minute. The conjoint contingencies were
      operative until, through session-shortening responses and the passage of time,
      the session was scheduled to end in two minutes; during the final two minutes the
      session-shortening contingency was disabled while the shock-postponement
      contingency continued to be operative on both levers. When responding shifted to
      a predominance on the session-shortening lever, the conjoint contingency was
      shifted to the other lever; for four of the five rats this reversal was followed
      by two additional reversals. Two of the rats' responding showed clear, strong,
      and unambiguous sensitivity to the session-shortening contingency. The responding
      of two others was also systematically controlled by that contingency, but the
      effects were less clearcut. The fifth animal showed an initial shift when session
      shortening was introduced, but its subsequent behavior proved insensitive to
      reversals of procedure. The results clearly indicate a sensitivity of behavior to
      events on a time scale quite distinct from that of immediate consequences. They
      also support an interpretation of avoidance sessions, considered in their
      entirety, as events whose contingent relationship to behavior can affect that
      behavior-even in the absence of stimuli that delineate those relationships.
      Finally, these results support an interpretation of aversively based conditioning
      within a broader context, analogous to the "open versus closed economy"
      interpretation of appetitively controlled behavior.

PMID- 16812338
TI  - The development of derived stimulus relations through training in arbitrary
      matching sequences.
AB  - Five-year-old children were taught three-stage sequences of arbitrary matching: A
      C, B-C, A-D; A-C, B-D, B-C; or A-C, A-D, B-C. Each stage refers to a sample
      comparison relation between stimuli. Unreinforced test probes revealed untrained
      arbitrary matches (B-D, A-D, and B-D, respectively), derivable by substitution of
      stimuli with a common sample or comparison function. Additional probes revealed
      further untrained sample-comparison relations derivable by substitution and
      identity, including the commuted relations D-B, D-A, and D-B, respectively. These
      processes may have relevance to conceptual and verbal behavior.

PMID- 16812339
TI  - Local rates of responding and reinforcement during concurrent schedules.
AB  - The literature was searched for information about the local rates of responding
      and reinforcement during concurrent schedules. The local rates of reinforcement
      obtained from the two components of a concurrent schedule were equal when a long
      duration changeover delay was used and when many sessions were conducted, except
      when the two components provided different simple schedules. The local rates of
      responding were equal under some conditions, but they differed when one component
      provided a ratio and the other an interval schedule. Across schedules, local
      rates of reinforcement changed with changes in the schedule of reinforcement.
      Local rates of responding did not change with changes in change-over-delay
      duration but did with changes in the changeover ratio and with changes in the
      programmed rates of reinforcement. The results generally conform to the
      Equalizing and Melioration Principles and help to clarify current statements of
      the Matching Law. The results also suggest that changes in the local rates of
      responding and reinforcement may be orderly across schedules.

PMID- 16812340
TI  - Stimulus-food relations and free-operant postponement of timeout from response
      independent food presentation.
AB  - Grain was briefly presented to food-deprived pigeons intermittently and response
      independently except during signaled timeouts. During Experiment 1, key pecks
      postponed the next timeout for a specified interval. Rates of pecking during time
      in were inversely related to the length of time pecking postponed the next
      timeout. Response-independent presentation of temporal distributions of timeouts
      exactly matched to a preceding postponement condition decreased pecking rates
      during Experiment 2. These results indicate that key pecking of pigeons can be
      controlled by response-dependent postponement of timeout, but that responses
      elicited by stimulus-reinforcer relations inherent in timeout-postponement
      procedures may substantially modify rates and patterns of pecking.

PMID- 16812341
TI  - An interresponse-time analysis of responding maintained by schedules of response
      produced electric shock.
AB  - The present study investigated ratio contingencies to evaluate factors that may
      determine the maintenance of responding when electric shock is the consequent
      event. Initially, squirrel monkeys (Saimiri sciureus) were exposed to a
      continuous-avoidance schedule to initiate bar pressing. Subsequently, a multiple
      random-interval variable-ratio yoked schedule of response-produced shock was used
      to maintain and to compare interval and ratio performance. A microcomputer
      recorded and stored the number of responses and interresponse times occurring
      between successive shock presentations during a given random-interval component,
      and these numbers determined the ratio requirements during the subsequent ratio
      component. Responding was maintained for more than 80 sessions in two of three
      monkeys under the multiple schedule with the ratio yoked to the interval
      component. Responding during the ratio component persisted in only one monkey,
      however, when the components were no longer yoked. An analysis of the
      interresponse times immediately preceding shock under the multiple yoked schedule
      revealed that the terminal interresponse times were longer under the interval
      schedule than under the ratio contingency. The interresponse-time analysis
      indicated that differential interresponse-time relationships may be major
      determinants of the maintenance of behavior controlled by schedules of electric
      shock presentation.

PMID- 16812342
TI  - Fast acquisition of cooperation and trust: A two-stage view of trusting behavior.
AB  - Trustful behavior was defined in terms of the consecutive numbers of matching-to
      sample problems worth money that each subject worked during sessions that ended
      in an equitable distribution. Two stages of acquisition are inherent in this
      definition; the first stage requires acquisition of an equitable method of
      distributing reinforcers (cooperation) to show that the within-session deviations
      (trust) from equity that develop during the second stage are temporary and are
      not part of an inequitable method of distributing reinforcers. Previous research
      has indicated that a contingency to trust is necessary to override the
      aversiveness of the inequity inherent in trusting and to produce consistent and
      maximal trust (half of the problems worked consecutively by each subject). The
      present experiment examined such a contingency. The trust contingency was an
      increased requirement for changing the direction of problem allocation. Only the
      subject who had been allocated a problem could change that allocation, by pulling
      a lever 45 or more times. On the other hand, no separate responses were required
      to allow the person who worked the last problem to also work the next one
      (passive trust). Hence, giving a problem was the only way to increase the
      distribution of problems to the other person and hence prevent oneself from
      receiving all of the reinforcers. All eight pairs of subjects cooperated from the
      outset. Trusting behavior developed for all four pairs exposed to the contingency
      to trust and expanded to maximal levels by the second session for three of the
      four pairs.

PMID- 16812343
TI  - Human observing: Maintained by stimuli correlated with reinforcement but not
      extinction.
AB  - College students received points exchangeable for money (reinforcement) on a
      variable-time 60-second schedule that alternated randomly with an extinction
      component. Subjects were informed that responding would not influence either the
      rate or distribution of reinforcement. Instead, presses on either of two levers
      ("observing responses") produced stimuli. In each of four experiments, stimuli
      positively correlated with reinforcement and/or stimuli uncorrelated with
      reinforcement were each chosen over stimuli correlated with extinction. These
      results are consistent with prior results from pigeons in supporting the
      conditioned-reinforcement hypothesis of observing and in not supporting the
      uncertainty-reduction hypothesis.

PMID- 16812344
TI  - Depriving rats of food: A reappraisal of two techniques.

PMID- 16812345
TI  - Remembering robert berryman (1921-1982).

PMID- 16812346
TI  - Choice for aperiodic versus periodic ratio schedules: A comparison of concurrent
      and concurrent-chain procedures.
AB  - Choice between mixed-ratio schedules, consisting of equiprobable ratios of 1 and
      99 responses per reinforcement, and fixed-ratio schedules of food reinforcement
      was assessed by two commonly used procedures: concurrent schedules and concurrent
      chains schedules. Rats were trained under concurrent fixed-ratio mixed-ratio
      schedules, in which both ratio schedules were simultaneously available, and under
      a concurrent-chains schedule, in which access to one of the mutually exclusive
      ratio schedules comprising the terminal links was contingent on a single "choice"
      response. The distribution of responses between the two ratio schedules was taken
      as the choice proportion under the concurrent procedure, and the distribution of
      "choice" responses was taken as the choice proportion under the concurrent-chains
      procedure. Seven of eight rats displayed systematic choice; of those, each
      displayed nearly exclusive choice for fixed-ratio 35 to the mixed-ratio schedule
      under the concurrent procedure, but each displayed nearly exclusive choice for
      the mixed-ratio schedule to fixed-ratio 35 under the concurrent-chains procedure.
      Thus, preference for a fixed or a mixed schedule of reinforcement depended on the
      procedure used to assess preference.

PMID- 16812347
TI  - On the effects of food deprivation and component reinforcer rates on multiple
      schedule performance.
AB  - Six pigeons were used to investigate the effects of varying body weight and
      component reinforcer rates in two-component multiple variable-interval variable
      interval schedules. In Parts 1 and 3 of the experiment, unequal component
      reinforcer rates were arranged, and body weights were respectively increased and
      decreased. At 80% ad lib weight, response-rate ratios were closer to unity than
      reinforcer-rate ratios, but at 100% or more of ad lib weight, response-rate
      ratios generally equaled reinforcer-rate ratios. In Part 2, component reinforcer
      rate ratios were varied over five conditions with the subjects maintained at 100%
      or more of their ad lib weights, and response-rate ratios matched reinforcer-rate
      ratios. The data thus support the empirical finding that response allocation in
      multiple schedules is a function of deprivation. Although this qualitative result
      is predicted by three models of multiple-schedule performance, only a model that
      assumes no direct component interaction adequately describes the data.

PMID- 16812348
TI  - Separating the effects of salience and disparity on the rate of observing.
AB  - Pigeons producing deliveries of grain on a mixed variable-interval, extinction
      schedule by pecking a center key could also produce discriminative stimuli on
      concurrent variable-interval schedules by pecking the left or right observing
      key. The stimuli produced by each observing key were varied independently. In the
      first experiment, the negative discriminative stimulus was at the far end of the
      spectrum from the key illumination accompanying the mixed schedule and from the
      positive discriminative stimulus. When the magnitude of the difference between
      the latter two stimuli (salience) was varied, more pecks occurred on the
      observing key producing the larger of the two differences than on the key
      producing the smaller difference. In the second experiment, the stimulus
      accompanying the mixed schedule was at the far end of the spectrum, and the
      magnitude of the difference between the two discriminative stimuli (disparity)
      was varied. The proportion of pecks occurring on each observing key shifted
      systematically in the direction of the key producing the larger difference. The
      salience of the discriminative stimuli and their disparity each has an
      independent influence on the frequency of observing when the other is controlled,
      but the effect of the salience appears to be the more substantial.

PMID- 16812349
TI  - Factors affecting choice of signaled or unsignaled food schedules.
AB  - Choice between signaled and unsignaled food schedules was assessed in two
      experiments using a shuttlebox. Experiment 1 examined preference with both a five
      second signal and a thirty-second signal. Subjects preferred the unsignaled side
      with a five-second signal but preferred the signaled side with a thirty-second
      signal. Experiment 2 assessed preference using either a commitment procedure (a
      shuttle response resulted in exposure to the schedule for a fixed time) or a
      noncommitment procedure (each shuttle response changed the schedule in effect).
      Subjects preferred the signaled condition with the commitment procedure but the
      unsignaled condition with the noncommitment procedure. These results indicate
      that the discrepant findings of earlier studies are due to procedural differences
      involving signal duration and choice commitment. The data are consistent with a
      conditioned reinforcement interpretation of choice.

PMID- 16812350
TI  - Matching, maximizing, and hill-climbing.
AB  - In simple situations, animals consistently choose the better of two alternatives.
      On concurrent variable-interval variable-interval and variable-interval variable
      ratio schedules, they approximately match aggregate choice and reinforcement
      ratios. The matching law attempts to explain the latter result but does not
      address the former. Hill-climbing rules such as momentary maximizing can account
      for both. We show that momentary maximizing constrains molar choice to
      approximate matching; that molar choice covaries with pigeons' momentary
      maximizing estimate; and that the "generalized matching law" follows from almost
      any hill-climbing rule.

PMID- 16812351
TI  - Undermatching and overmatching as deviations from the matching law.
AB  - A model of performance under concurrent variable-interval reinforcement schedules
      that takes as its starting point the hypothetical "burst" structure of operant
      responding is presented. Undermatching and overmatching are derived from two
      separate, and opposing, tendencies. The first is a tendency to allocate a certain
      proportion of response bursts randomly to a response alternative without regard
      for the rate of reinforcement it provides, others being allocated according to
      the simple matching law. This produces undermatching. The second is a tendency to
      prolong response bursts that have a high probability of initiation relative to
      those for which initiation probability is lower. This process produces
      overmatching. A model embodying both tendencies predicts (1) that undermatching
      will be more common than overmatching, (2) that overmatching, when it occurs,
      will tend to be of limited extent. Both predictions are consistent with available
      data. The model thus accounts for undermatching and overmatching deviations from
      the matching law in terms of additional processes added on to behavior allocation
      obeying the simple matching relation. Such a model thus enables processes that
      have been hypothesized to underlie matching, such as some type of reinforcement
      rate or probability optimization, to remain as explanatory mechanisms even though
      the simple matching law may not generally be obeyed.

PMID- 16812352
TI  - Teaching sign language to a chimpanzee: Some historical references.

PMID- 16812353
TI  - The state of the art and the fate of the earth.
AB  - A recent review by Nevin of Jonathan Schell's The Fate of the Earth applies a
      "behavioral perspective" to the problem of species survival in a nuclear age. It
      is suggested that no perspective, in this context as in others where less is at
      stake, should dismiss prematurely some useful ideas from other perspectives. A
      sampling of "cognitive" concepts is offered to illustrate what actions, aimed at
      resisting species extinction, might follow from them-not instead of, but in
      addition to, the guidelines for action a behavioral perspective provides.

PMID- 16812354
TI  - Editorial.

PMID- 16812355
TI  - The assumptions underlying the generalized matching law.
AB  - Allen (1981) derived the power-function generalization of the matching law from a
      functional equation involving relative response rates on three concurrently
      available schedules of reinforcement. This paper defines the conditions (relative
      homogeneity and independence) under which a more general class of behavioral laws
      reduces to the power law. The proof also removes two deficiencies of Allen's
      result (discussed by Houston, 1982), which are, first, that his derivation
      produces a power law without a bias coefficient, and second, that it holds only
      for experiments with three or more concurrent schedules.

PMID- 16812356
TI  - Graded differential reinforcement: Response-dependent reinforcer amount.
AB  - After key pecking had been autoshaped, six pigeons were exposed to a condition in
      which the duration of grain availability at the end of an 8-second trial depended
      on the number of responses emitted during the trial (0.25-second access to grain
      per response). This procedure, called correlated reinforcement, alternated across
      conditions with the automaintenance baseline in which the 8-second trial
      terminated with a constant 2.5-second access to grain. Two control procedures
      were run; in both, the reinforcer durations were yoked to those obtained in the
      last correlated session. In the yoked control no responses were required, but in
      the single-response yoked control at least one response was required to receive
      the yoked duration. The correlated condition maintained response rates above
      those produced by the two control conditions. These results may be accounted for
      by differential reinforcement.

PMID- 16812357
TI  - Preference for signaled over unsignaled shock schedules: Ruling out asymmetry and
      response fixation as factors.
AB  - Experiment 1 tested whether a "symmetrical" choice procedure yields results
      different from those previously reported using the "unidirectional" standard
      changeover procedure (e.g., Badia & Culbertson, 1972). Subjects could change at
      any time from unsignaled to signaled shock by pressing a lever and from signaled
      to unsignaled shock by pressing a second lever. Results were identical to those
      of the standard procedure and showed that the standard procedure is fully
      adequate. Experiment 2 tested whether choice of high density signaled shock over
      low-density unsignaled shock (Badia, Coker, & Harsh, 1973) resulted from initial
      training with equal-density schedules. Subjects were trained and tested with
      signaled shock twice as dense as unsignaled shock. Three of four subjects
      strongly preferred the signaled condition, thus ruling out carry-over and
      "response fixation" as alternative explanations.

PMID- 16812358
TI  - Choice in a self-control paradigm: Quantification of experience-based
      differences.
AB  - Previous quantitative models of choice in a self-control paradigm (choice between
      a larger, more-delayed reinforcer and a smaller, less-delayed reinforcer) have
      not described individual differences. Two experiments are reported that provide
      additional quantitative data on experience-based differences in choice between
      reinforcers of varying sizes and delays. In Experiment 1, seven pigeons in a self
      control paradigm were exposed to a fading procedure that increased choices of the
      larger, more-delayed reinforcer through gradually decreasing the delay to the
      smaller of two equally delayed reinforcers. Three control subjects, exposed to
      each of the small-reinforcer delays to which the experimental subjects were
      exposed, but for fewer sessions, demonstrated that lengthy exposure to each of
      the conditions in the fading procedure may be necessary in order for the increase
      to occur. In Experiment 2, pigeons with and without fading-procedure exposure
      chose between reinforcers of varying sizes and delays scheduled according to a
      concurrent variable-interval variable-interval schedule. In both experiments,
      pigeons with fading-procedure exposure were more sensitive to variations in
      reinforcer size than reinforcer delay when compared with pigeons without this
      exposure. The data were described by the generalized matching law when the
      relative size of its exponents, representing subjects' relative sensitivity to
      reinforcer size and delay, were grouped according to subjects' experience.

PMID- 16812359
TI  - Stimulus and reinforcer relativity in multiple schedules: Local and dimensional
      effects on sensitivity to reinforcement.
AB  - Pigeons' responses in two successive components of multiple schedules were
      reinforced according to variable-interval schedules of reinforcement that varied
      over five different conditions. Within each session of all conditions, line
      orientations of 0 degrees , 30 degrees , or 45 degrees in Component 1 alternated
      with orientations of 45 degrees , 60 degrees , or 90 degrees in Component 2.
      Response rates were recorded in three successive subintervals of each component.
      Ratios were taken between the response rate in each Component 1 line orientation
      and the response rate in each Component 2 orientation. These ratios were found to
      be power functions of the corresponding ratios of obtained reinforcement rates.
      Sensitivity of response ratios to changes in reinforcer ratios, given by the
      value of the exponent of the power function, increased systematically with
      increasing disparity between the dimensional values of orientation stimuli. In
      addition, sensitivity decreased systematically over successive subintervals of
      components, that is, with increasing time since component alternation.
      Dimensional and local (subinterval) effects interacted in that sensitivity
      increased with stimulus disparity to a far greater extent in the first
      subinterval than later in components. The data could be described by a
      combination of rectangular hyperbolae which attributed the interaction between
      local and dimensional effects to limits set by local effects on the extent that
      stimulus differences could affect sensitivity.

PMID- 16812360
TI  - Concurrent variable-interval variable-ratio schedules can provide only weak
      evidence for matching.
AB  - Herrnstein and Heyman (1979) showed that when pigeons' pecking is reinforced on
      concurrent variable-interval variable-ratio schedules, (1) their behavior ratios
      match the ratio of the schedules' reinforcer frequencies, and (2) there is more
      responding on the variable interval. Since maximizing the reinforcement rate
      would require responding more on the variable ratio, these results were presented
      as establishing the primacy of matching over maximizing. In the present report,
      different ratios of behavior were simulated on a computer to see how they would
      affect reinforcement rates on these concurrent schedules. Over a wide range of
      experimenter-specified choice ratios, matching obtained - a result suggesting
      that changes in choice allocation produced changes in reinforcer frequencies that
      correspond to the matching outcome. Matching also occurred at arbitrarily
      selected choice ratios when reinforcement rates were algebraically determined by
      each schedule's reinforcement-feedback function. Additionally, three birds were
      exposed to concurrent variable-interval variable-ratio schedules contingent on
      key pecking in which hopper durations were varied in some conditions to produce
      experimenter-specified choice ratios. Matching generally obtained between choice
      ratios and reinforcer-frequency ratios at these different choice ratios. By
      suggesting that reinforcer frequencies track choice on this procedure, instead of
      vice versa, this outcome questions whether matching-as-outcome was due to
      matching-as-process in the Herrnstein and Heyman study.

PMID- 16812361
TI  - A temporal limit on the effect of future food on current performance in an
      analogue of foraging and welfare.
AB  - Rats obtained access to food twice each 24-hour period. The first session was a
      work session in which food was available on a progressive-ratio schedule. During
      the second session, which occurred between 1 and 23 hours after the work session,
      food was freely available up to a fixed total intake each 24 hours. The situation
      resembled elements of several real world circumstances, including the choice
      between continuing to forage in a rapidly depleting patch and waiting for a
      better patch, and between working now and receiving a guaranteed income later.
      The purpose of the experiment was to explore the time period over which future
      access to reward could affect current responding. Contrary to what might be
      expected from recent theorizing, anticipation of future food delayed by an hour
      or more after the start of the work session had no effect on current performance.
      Food intake was high and constant during work sessions except for a prefeeding
      effect that occurred when the free session closely preceded the next day's work
      session. Also, an increase in the difficulty of the work schedule increased the
      amount of work and the maximum price paid for food as if the work session were
      the only time food was available. The results indicate the importance of
      considering temporal limits in theories that require animals to integrate input
      over time to determine the allocation of resources among alternatives.

PMID- 16812362
TI  - A parametric analysis of the relationship between food quantity and rumination.
AB  - Rumination is the chronic regurgitation, chewing, and reswallowing of previously
      ingested food. The study reported here, using a parametric design, examined the
      control of rumination by the quantity of food eaten at meals. The subjects were
      three profoundly retarded individuals who chronically emitted this behavior. The
      quantity of food by weight ingested daily was varied in 10-oz steps in both
      ascending and descending series (data were collected only after breakfasts and
      lunches). Ruminating decreased when food quantity increased and increased when
      food quantity decreased. In addition, there was a similar inverse interaction
      between breakfast food quantity and post-lunch ruminating. The data showed
      relatively rapid transitions in both frequency and duration at each meal size for
      all subjects. The data establish a clear functional relation between the quantity
      of food ingested and ruminating.

PMID- 16812363
TI  - The effects of delayed reinforcement on free-operant responding.
AB  - In previous studies of delayed reinforcement, response rate has been found to
      vary inversely with the response-reinforcer interval. However, in all of these
      studies the independent variable, response-reinforcer time, was confounded with
      the number of reinforcers presented in a fixed period of time (reinforcer
      frequency). In the present study, the frequency of available reinforcers was held
      constant, while temporal separation between response and reinforcer was
      independently manipulated. A repeating time cycle, T, was divided into two
      alternating time periods, t(D) and t(Delta). The first response in t(D) was
      reinforced at the end of the prevailing T cycle and extinction prevailed in
      t(Delta). Two placements for t(D) were defined, an early t(D) placement in which
      t(D) precedes t(Delta) and a late t(D) placement in which t(D) follows t(Delta).
      The duration of the early and late t(D) was systematically decreased from 30
      seconds (i.e., t(D) = T) to 0.1 second. Manipulation of t(D) placement and
      duration controlled the temporal separation between response and reinforcement,
      but it did not affect the frequency of programmed reinforcers, which was 1/T. The
      results show that early and late t(D) placements of equal duration have similar
      overall effects upon response rate, reinforcer frequency, responses per
      reinforcer, and obtained response-reinforcer temporal separation. A stepwise
      regression analysis using log response rate as the dependent variable showed that
      the obtained delay was a significant first-step variable for six of eight
      subjects, with obtained reinforcer frequency significant for the remaining two
      subjects.

PMID- 16812364
TI  - Frequency versus magnitude of reinforcement: New data with a different procedure.
AB  - Two pigeons, with previous exposure to concurrent schedules, were submitted to 29
      sessions of 8 hours each with concurrent variable-interval variable-interval
      schedules in which reinforcement parameters changed from session to session. In
      the first nine sessions reinforcement durations were equal in both schedules
      while reinforcement frequencies varied; in Sessions 10 through 18, both frequency
      and duration of reinforcement were varied; in Sessions 19 through 29, only
      reinforcement duration was varied. Results with this different procedure confirm
      previous findings that behavior is more sensitive to changes in reinforcement
      frequency than to reinforcement magnitude.

PMID- 16812365
TI  - Concurrent variable-interval schedule performance: Fixed versus mixed reinforcer
      durations.
AB  - Six pigeons were trained on concurrent variable-interval schedules. Two different
      reinforcer durations were arranged on the left key, and which of these was
      delivered was determined probabilistically. A single reinforcer duration was
      arranged on the right key. In Parts 1 and 3 of the experiment, the probability of
      the left-key reinforcer durations (1 and 7 seconds in Part 1; 3 and 10 seconds in
      Part 3) was varied from 0 to 1, keeping the schedules constant and the right-key
      reinforcer at 3 seconds. Response allocation to the left key fell as the
      probability of the shorter left-key reinforcer duration was increased. In Part 2,
      one left-key reinforcer duration was 3 seconds and the other was varied from 0 to
      10 seconds, while again the schedules and right-key reinforcer duration (3
      seconds) were kept constant. Left-key response allocation increased as the varied
      reinforcer duration on the left key increased. An extension of the generalized
      matching law failed to provide a good description of response allocation in these
      procedures. In Part 4, the left- and right-key reinforcer durations were 3
      seconds and the variable-interval schedules were varied. Response allocation was
      well described by the generalized matching law. Part 5 arranged equal variable
      interval schedules on the left and right keys, 3-second reinforcers on the right
      key, and the left-key reinforcer durations were varied from 1 to 10 seconds. The
      relationship between the log response and reinforcer-duration ratios was
      nonlinear. The effects of varying reinforcer durations in concurrent schedules
      cannot be described using the generalized matching law with constant parameters.
      It is suggested more generally that this quantitative relation may not describe
      performance either when reinforcing situations differ in duration (e.g., with
      delayed reinforcers) or when response requirements differ in duration.

PMID- 16812366
TI  - Confirmation of linear system theory prediction: Changes in Herrnstein's k as a
      function of changes in reinforcer magnitude.
AB  - Eight human subjects pressed a lever on a range of variable-interval schedules
      for 0.25 cent to 35.0 cent per reinforcement. Herrnstein's hyperbola described
      seven of the eight subjects' response-rate data well. For all subjects, the y
      asymptote of the hyperbola increased with increasing reinforcer magnitude and its
      reciprocal was a linear function of the reciprocal of reinforcer magnitude. These
      results confirm predictions made by linear system theory; they contradict formal
      properties of Herrnstein's account and of six other mathematical accounts of
      single-alternative responding.

PMID- 16812367
TI  - Choice for conditioned reinforcers in the signaled absence of primary
      reinforcement.
AB  - Pigeons responded in a multiple schedule in which concurrent schedules of brief
      stimulus presentation alternated with a component in which food was available
      (concurrent-chains component). In the initial links of the concurrent-chains
      component subjects chose either of two stimuli each correlated with the terminal
      link of one chain. The terminal links involved either variable-interval 30-second
      or variable-interval 60-second schedules. In the brief-stimulus component
      subjects chose between 0.5-second presentations of the terminal-link stimuli from
      the concurrent-chains component. Responding was generally maintained in the brief
      stimulus component in two subjects for more than 300 sessions, suggesting that
      brief stimuli were conditioned reinforcers. During the brief-stimulus component,
      in 17 of 21 cases for which a minimal number of responses occurred, choice
      proportions above 0.55 were obtained for the brief-stimulus presentations
      correlated with the higher rate of primary reinforcement in the concurrent-chains
      component. These results support the suggestion that choice in conventional
      concurrent-chains procedures is partially controlled by production of the
      terminal-link stimuli.

PMID- 16812368
TI  - Separating response dependency and response-reinforcer contiguity within a
      recycling conjunctive schedule.
AB  - A procedure is described which disrupts response-reinforcer contiguity and
      response dependency and which demonstrates how the location of the response
      dependency in interval schedules can be regarded as a controlling variable in its
      own right. Rats' lever pressing produced sucrose on a recycling conjunctive fixed
      time 30-second fixed-ratio 1 schedule of reinforcement. Reinforcement occurred
      only at the end of the fixed-time component on this schedule and only if a
      response had occurred during that component. This produced a pause-respond-pause
      pattern during the interreinforcer interval for all animals. When the location of
      the response dependency was then restricted to a 10-second period in the middle
      of the fixed-time component, the pattern was accentuated and response rates
      increased for all animals, while postreinforcement pauses decreased sharply for
      two animals. When responding was required in the first 10 seconds of the fixed
      time component, responding peaked earlier in the interval for all animals.
      Response rates were slightly below those in the previous conditions, while
      postreinforcement pauses were between 2 and 6 seconds across animals.

PMID- 16812369
TI  - Verbal behavior at a procedural level in the chimpanzee.
AB  - Ape language research has typically employed cognitive descriptions of ape
      competencies. Recently, Epstein, Lanza, and Skinner (1980) attempted to simulate
      some of the ape findings with pigeons. They also used cognitive terms to describe
      their results, but with "tongue-in-cheek." In the hope of bringing about a better
      understanding of the ape research, this paper describes the main aspects of one
      ape language project, using a behavior-analytic framework. It then briefly
      compares and contrasts, from that perspective, the training programs used with
      pigeons and with apes. It is concluded that the behavior-analytic framework, and
      the procedures devised to produce language skills in apes, provide strong support
      for several of the major positions set forth in Skinner's (1957) Verbal Behavior.

PMID- 16812370
TI  - Time reallocation in a multiresponse environment: Effects of restricting response
      classes.
AB  - Four adult male rats were each placed for three hours daily into an apparatus
      that provided individual compartments for six separate location-defined
      responses. The available responses consisted of: (1) the opportunity to turn off
      room lighting, producing darkness; (2) the opportunity to view a female rat; (3)
      the opportunity to turn off white noise; (4) the opportunity to drink; (5) the
      opportunity to eat; and (6) "other," representing time in the hallway between
      compartments. Each subject underwent a series of conditions characterized as an A
      B-A-C-A design. Manipulations consisted of the removal of a low-probability
      response (darkness) and of a high-probability response (escape from noise) in a
      counter-balanced manner across subjects. The dependent measure for all subjects
      was the percentage of total session time spent in each compartment. Four
      predictive rules concerning the redistribution of behavior after response
      restriction were tested, including the constant-ratio rule, equal time
      redistribution, the most probable alternative, and the sequential-dependency
      rule. The results indicate no support for any of the four predictive rules and
      suggest that empirical assessment of restriction effects is necessary in
      reinforcement studies involving temporally extended responses.

PMID- 16812371
TI  - Choosing between predictable shock schedules: Long- versus short-duration
      signals.
AB  - Two experiments assessed the relative aversiveness of different duration preshock
      signals (5 and 20 seconds) and different duration stimuli identifying shock-free
      periods. In the first experiment, the responding of 15 of 18 rats was maintained
      when it produced changes from a predictable-shock condition with a 5-second
      preshock signal to an identical schedule with a 20-second preshock signal;
      responding was not maintained when it produced the opposite changes. These
      results occurred with intershock intervals of both 120 seconds and 240 seconds.
      The second experiment assessed whether changing to the 20-second schedule was
      maintained by properties of the preshock signals identifying the shock periods or
      by properties of the stimuli identifying the shock-free periods. Four subjects
      were given training with the two signaled schedules in an operant chamber and
      then later given off-baseline preference tests in a shuttlebox. When given a
      choice between preshock signals, subjects chose the 5-second signals over the 20
      second signals. However, when given a choice between stimuli identifying shock
      free periods, subjects chose the stimulus identifying the shorter shock-free
      periods (i.e., the one previously correlated with the 20-second signals). These
      findings are discussed within the Rescorla and Wagner model of stimulus compounds
      and within the context of safety as a contrast phenomenon.

PMID- 16812372
TI  - Editorial comments.

PMID- 16812373
TI  - Comments on Shimp's (1983) double dissociation between knowledge and tacit
      knowledge.
AB  - Shimp (1983) found in five pigeons "double dissociation" between the distribution
      of pairs of long and short reinforced interresponse times and "self-reports,"
      obtained by symbolic matching to sample, concerning these interresponse times.
      This result can be explained by assuming that the birds used a fixed temporal
      interval as matching criterion, independently of which pattern of interresponse
      times was reinforced.

PMID- 16812374
TI  - Behavior regulation and learned performance: Some misapprehensions and
      disagreements.
AB  - The behavior-regulation approach to learned performance has been the subject of
      misapprehension and disagreement concerning: (1) the nature and importance of
      behavior regulation, (2) the definition and role of behavioral set-points, (3)
      the relation of optimal schedule performance to behavioral set-points, and (4)
      the question of whether deviations from total responding or from response
      patterns are the primary determinant of molar responding under schedule
      constraint. After clarifying the nature and role of behavior regulation and set
      points, this paper shows that the data used to question optimal schedule
      performance (Allison, 1981a) actually strongly support the general behavior
      regulation approach. These data also indicate a role for response-pattern set
      points in determining schedule behavior, but contradict the hypothesis that
      deviations from response-pattern characteristics are the primary determinant of
      molar schedule effects.

PMID- 16812375
TI  - Reviewers' comments on Timberlake's "Behavior regulation and learned
      performance".

PMID- 16812376
TI  - Further thoughts on behavior regulation.

PMID- 16812377
TI  - Melloration and maximization of reinforcement minus costs of behavior.
AB  - Eight pigeons were exposed to independent concurrent schedules. Concurrent
      variable-interval 60-second variable-interval 60-second schedules were presented
      to one group of four subjects. Following baseline training, a limited hold was
      added to one of the schedules and the duration of the hold was decreased in
      successive conditions. Concurrent variable-interval 120-second variable-interval
      40-second schedules were presented to another group of four subjects. These
      subjects were first exposed to decreasing durations of a limited hold in the
      variable-interval 40-second component. After replication of the baseline, a
      limited hold in the variable-interval 120-second component was decreased in
      duration. The initial durations of the holds were determined from the subjects'
      responding in the baseline conditions. A duration was chosen such that
      approximately 25% of the scheduled reinforcers would be canceled if responding
      remained unchanged.Approximate matching of time proportions and reinforcement
      proportions was observed when the limited hold was added to the variable-interval
      60-second schedule and when the limited hold was added to the variable-interval
      40-second schedule. Time proportions were less extreme than reinforcement
      proportions when the limited hold operated in a variable-interval 120-second
      schedule. Overall reinforcement rates tended to decrease with continued training
      in concurrent schedules with a limited hold. Absolute deviations from time
      matching also decreased. The results provide evidence against the principle of
      reinforcement maximization, and support Herrnstein and Vaughan's (1980)
      melioration hypothesis.

PMID- 16812378
TI  - Preference in pigeons given a choice between sequences of fixed-ratio schedules:
      Effects of ratio values and duration of food delivery.
AB  - Pigeons were exposed to schedules that consisted of two sequential fixed ratios,
      the completion of each followed by food delivery. When each alternative provided
      two food deliveries per 100 responses, the schedule with the shorter initial
      fixed-ratio value was consistently preferred. Subsequent attempts were made to
      shift this established preference by (1) increasing the ratio requirement in the
      second fixed ratio of the preferred schedule; (2) increasing the duration of food
      delivery in the second fixed ratio of the nonpreferred schedule; (3) decreasing
      the duration of food delivery in the first fixed ratio of the preferred schedule;
      and (4) shortening the second fixed ratio of the nonpreferred schedule.
      Preference shifted from the schedule with the shorter initial fixed ratio only
      when the duration of food delivery associated with the first fixed ratio of that
      schedule was too brief to allow eating. Under all other conditions, pigeons
      strongly preferred the schedule with the shorter initial fixed ratio even when,
      overall, that schedule yielded briefer access to food or required more responses
      to obtain equivalent access.

PMID- 16812379
TI  - The double-alternative, double-start experimental apparatus: A new procedure for
      measuring preference.
AB  - A new experimental chamber is described that permits rats to demonstrate
      behavioral preference for one of two conditions by running towards a goal chamber
      by one of two routes that are correlated with the different conditions. In a
      preliminary study, rats chose a route correlated with relatively lower shock,
      demonstrating the sensitivity of the apparatus. We also report evidence using
      this device that, of 10 rats tested, all preferred unsignaled rather than
      signaled, inescapable, unavoidable shock.

PMID- 16812380
TI  - Stimulus equivalence and transitive associations: A methodological analysis.
AB  - When a number of two-stimulus relations are established through training within a
      set of stimuli, other two-stimulus relations often emerge in the same set without
      direct training. These, termed "transitive stimulus relations," have been
      demonstrated with a variety of visual and auditory stimuli. The phenomenon has
      served as a behavioral model for explaining the emergence of rudimentary
      comprehension and reading skills, and the development of generative syntactic
      repertoires. This article considers the range of relations that can arise between
      a given number of stimuli in a class, the number of directly established two
      stimulus relations necessary for the emergence of transitive relations, the forms
      that training sets of stimuli can take, and the number of transitive two-stimulus
      relations that can be induced without direct training. The procedures needed to
      establish and assess transitive stimulus control, the possible interactions
      between the training and testing procedures, and the constrainst these
      interactions place upon the analysis of transitive stimulus control are also
      examined. The present analysis indicates that in a transitivity test, choice
      among such stimuli may be controlled by (1) the relation between the sample and
      the positive comparison stimulus (transitive stimulus control), (2) the relation
      between the sample and the negative comparison stimulus (S- rule control), and
      (3) possible discriminative properties that may inadvertently be established in
      the positive and negative comparison stimuli (valence control). Methods are
      described for distinguishing these three forms of stimulus control.

PMID- 16812381
TI  - Shock intensity and signaled avoidance responding.
AB  - Five rats were submitted to a signaled free-operant avoidance contingency.
      Throughout the experiment, shock intensity was varied from 0.1 to 8.0 mA, with
      shock duration constant at 200 milleseconds. Results indicate: (a) an all-or-none
      effect of shock intensity on response and shock rates, on percentage of shocks
      avoided, and on frequency of occurrence of responding during the preshock
      stimulus; and (b) no systematic effect of shock intensity on stimulus control,
      measured either by the percentage of stimulus presentations accompanied by a
      response or by the percentage of responses that occurred during those preshock
      stimuli. Such results indicate that for each subject there is a minimum shock
      intensity necessary to establish and maintain avoidance responding; intensities
      higher than this minimum value have little or no effect on responding (with an
      upper limit for those strong intensities with a general disruptive effect on
      behavior).

PMID- 16812382
TI  - Autocontingencies: Suppressive and accelerative effects of pairs of shocks
      superimposed on a positively reinforced operant baseline.
AB  - Previous research has shown that unsignaled shock may accelerate positively
      reinforced operant responding if each shock signals a subsequent shock-free
      period. In order to explore the boundary conditions of this effect, two
      experiments were performed. In Experiment 1, pairs of unsignaled shocks separated
      by 15, 30, 60, or 120 seconds resulted in suppressed responding during the
      briefest intershock interval, and in accelerated responding during the longer
      intervals. When the second shock in each pair signaled a shock-free period of at
      least 3 minutes, accelerated responding also followed offset of the second shock
      in all but the 30-second condition. In Experiment 2, the addition of a
      conditioned stimulus prior to each pair of shocks restored baseline responding,
      and eliminated accelerative control following the second shock only under the
      briefest inter-shock interval. The results are discussed in terms of the
      similarity between autocontingencies (shock/no-shock relations; Davis, Memmott, &
      Hurwitz, 1975) and recent modifications of the feature-positive procedure (e.g.,
      Reberg & Memmott, 1979), which stress stimulus control by shock/no-shock
      relationships.

PMID- 16812383
TI  - Editorial: Conceivable book reviews.

PMID- 16812384
TI  - Operant conditioning of autogrooming in vervet monkeys: Cercopithecus aethiops.
AB  - Vervet monkeys received food reinforcement contingent on autogrooming. Experiment
      1 reinforced grooming on a schedule of increasing intermittency and grooming
      increased in frequency and duration; with only pauses reinforced, grooming
      decreased in frequency and duration. Experiment 2 demonstrated differentiation of
      operant autogrooming; in each session a different single form of grooming was
      reinforced (for example, grooming the tail only), and that form increased in
      frequency while other forms became less frequent. In Experiment 3 scratching was
      succesfully conditioned with a method that selectively reinforced variety in
      behavior; reinforcement was contingent on a shift in scratching form. In
      Experiment 4, with no contingencies on grooming, a prefood stimulus did not
      increase autogrooming whether or not grooming had previously resulted in
      contingent reinforcement. The form of conditioned autogrooming resembled the form
      of unconditioned autogrooming. The discussion suggests how reinforcement
      principles can account for changes in the topography of operant behavior.

PMID- 16812385
TI  - Stimulus control of schedule-induced activity in pigeons during multiple
      schedules.
AB  - Stimulus control of schedule-induced general activity was demonstrated with
      pigeons using multiple schedules of response-independent food delivery. In
      Experiment 1, the introduction of food during a multiple variable-time 30-second
      variable-time 30-second schedule produced a tenfold increase in activity above
      the no-food baseline. Each pigeon developed stable differential activity rates
      during the components (correlated with red and green lights) of a multiple
      variable-time 30-second extinction schedule. Lengthening the extinction component
      from 1 to 7 minutes increased the rate differences and produced a reliable
      pattern of responding during S- (the stimulus correlated with extinction):
      Activity rate was high immediately following the change from S+ (the stimulus
      correlated with variable-time 30-second) to S-, then decreased abruptly and
      remained low throughout the middle of the interval, and subsequently showed a
      positively accelerated increase until the stimulus changed to S+. In Experiment
      2, three pigeons were exposed to a mixed variable-time extinction schedule prior
      to a multiple variable-time extinction schedule. Auditory rather than visual
      stimuli were used to determine the generality of Experiment 1 results. The
      multiple- versus mixed-schedule results indicated that stimulus control of
      activity occurred for two of the birds, but rate differences between S+ and S-
      were much less than those demonstrated with visual stimuli. A direct comparison
      of visual and auditory stimulus control in Experiment 3 supported this
      conclusion. These parallels between the stimulus control of reinforced responding
      and that of schedule-induced activity suggest that the stimulus control of
      induced activity may be a factor in operant stimulus control.

PMID- 16812386
TI  - Transfer of matching-to-figure samples in the pigeon.
AB  - Three pigeons were trained on a modified six-key matching-to-sample procedure.
      The third peck on the figure-sample key (which presented a bird, hand, face,
      beetle, rabbit, fish, flower, or red hue, as the sample) lighted only one
      comparison key. Every three additional pecks on the sample lighted another
      comparison key, up to a maximum of five keys. Pecks on keys of matching figures
      produced grain. Pecks on nonmatching keys (mismatches) turned off all lights on
      the comparison keys and repeated the trial. Three figures were used during
      acquisition. The birds learned to peck each sample until the matching comparison
      stimulus appeared on one of three comparison stimulus keys, and then to peck that
      key. Later, five novel stimuli, employed as both sample and comparison stimuli,
      and two additional matching keys were added. Each bird showed matching transfer
      to the novel samples. The data suggest that the birds may have learned the
      concept of figure matching rather than a series of two-component chains or
      discrete five-key discriminations.

PMID- 16812387
TI  - Signal functions in delayed reinforcement.
AB  - Three experiments were conducted with pigeons to examine the role of the signal
      in delay-of-reinforcement procedures. In the first, a blackout accompanying a
      period of nonreinforcement increased key-peck response rates maintained by
      immediate reinforcement. The effects of dissociating the blackout from the delay
      interval were examined in the second experiment. In three conditions, blackouts
      and unsignaled delays were negatively correlated or occurred randomly with
      respect to one another. A signaled delay and an unsignaled delay that omitted the
      blackouts were studied in two other conditions. All delay-of-reinforcement
      conditions generally produced response rates lower than those produced by
      immediate reinforcement. Signaled delays maintained higher response rates than
      did any of the various unsignaled-delay conditions, with or without dissociated
      blackouts. The effects of these latter conditions did not differ systematically
      from one another. The final experiment showed that response rates varied as a
      function of the frequency with which a blackout accompanied delay intervals. By
      eliminating a number of methodological difficulties present in previous delay-of
      reinforcement experiments, these results suggest the importance of the signal in
      maintaining responding during delay-of-reinforcement procedures and, conversely,
      the importance of the delay interval in decreasing responding.

PMID- 16812388
TI  - Effects on preference of reinforcement delay, number of reinforcers, and terminal
      link duration.
AB  - Three experiments used concurrent-chains procedures to examine the effects of
      reinforcement delay, number of reinforcers, and terminal-link duration on
      preference. In Condition 30 of Experiment 1, food was delivered after 30 seconds
      in each 150-second terminal link, with four additional food deliveries occurring
      at 30-second intervals in one of the links. In Condition 5, food was delivered
      after 5 seconds in each 25-second terminal link, and the four additional
      reinforcers were delivered at 5-second intervals. Preferences for the multiple
      food chain were greater in Condition 30. In Experiment 2, the terminal link(s)
      providing only one reinforcer terminated immediately after delivery of the
      reinforcer. Preferences for the multiple-food chain were smaller than in
      Experiment 1. In Condition 5 of Experiment 3, food was delivered after 5, 75,
      100, 125, and 150 seconds in one 150-second link and after 5 seconds in the
      other. Condition 50 differed only in that the first (or only) reinforcer in each
      link was delivered after 50 seconds instead of after 5 seconds. Preferences for
      the multiple-food chain were greater in Condition 50. Results of Experiments 1
      and 2 do not correspond to results obtained by Moore (1979).

PMID- 16812389
TI  - Temporal control by signals of interval duration within variable-interval
      schedules.
AB  - Rats' lever pressing produced sucrose reinforcers on a variable-interval schedule
      where, in different conditions, the duration of a stimulus presented immediately
      after reinforcement was either correlated or uncorrelated with the duration of
      the current interreinforcement interval. Under the baseline schedule, in which no
      stimulus was presented, the minimum interreinforcement interval was 8 s and the
      mean postreinforcement pause of each subject approximated this value. Response
      rates increased slowly over the first 10 to 15 s and then remained roughly
      constant throughout the remainder of the interval. In both the correlated and
      uncorrelated conditions, the added stimulus resulted in the postreinforcement
      pauses lengthening to values in excess of the duration of the preceding stimulus.
      This resulted in a poststimulus pause which was, in most cases, roughly constant
      irrespective of the duration of the preceding stimulus, or of the reinforcement
      contingencies prevailing immediately after stimulus offset. Local response-rate
      patterns in the uncorrelated conditions were similar to those obtained under the
      baseline schedule in which no stimulus was presented. However, in the correlated
      condition local response rates increased across the remainder of the
      interreinforcer interval. Further, the rate of acceleration was inversely related
      to the duration of the preceding stimulus. These results show that a correlation
      between stimulus duration and the ensuing time to reinforcement can control
      behavior-a type of temporal control not previously reported.

PMID- 16812390
TI  - Signal modality and choice between signaled and unsignaled food.
AB  - Choice between signaled and unsignaled response-independent food schedules was
      assessed in three experiments using a commitment procedure. In Experiment 1,
      subjects tested with a 5-s visual signal consistently changed from the signaled
      to the unsignaled schedule. Changing from the unsignaled to the signaled schedule
      was observed only occasionally and only at low levels. The same outcome was
      observed in Experiment 2 with different types of visual signals and with
      different stimulus combinations identifying the signal period, the signal-absent
      period, and the unsignaled schedule. In Experiment 3 the visual signal was
      replaced with an auditory signal for four of the subjects tested in Experiment 2.
      The subjects then changed from the unsignaled to the signaled schedule or showed
      a substantial reduction in choice for the unsignaled schedule. The data were
      assessed using a conditioned-reinforcement interpretation of choice.

PMID- 16812391
TI  - Interreinforcement time, work time, and the postreinforcement pause.
AB  - Six rats were trained with food deliveries contingent upon their pressing a lever
      and holding it down for fixed, cumulative durations. Hold requirements were
      varied from 7.5 seconds to 120 seconds. Lever holding was maintained reliably at
      hold requirements as long as 30 seconds to 105 seconds for different rats. At
      longer hold requirements, lever holding was erratic and tended to occur only
      early in sessions. At shorter and intermediate requirements, the patterns of
      lever holding resembled those of responding under fixed-ratio schedules for
      discrete responses, with breaks in responding immediately after reinforcement
      alternating with relatively continuous lever holding until the next
      reinforcement. At longer hold requirements, postpause lever holding frequently
      was interrupted with additional pauses. The duration of postreinforcement pauses
      increased linearly with the scheduled hold requirement. However, for five of six
      rats, the hold requirement, which represents the actual time spent lever holding
      per reinforcer, accounted for somewhat less variance in pause duration than did
      interreinforcement time.

PMID- 16812392
TI  - Choice and transformed interreinforcement intervals.
AB  - Pigeons chose between two aperiodic, time-based schedules of reinforcement. The
      arithmetic mean interreinforcement interval of the first schedule was short, but
      the harmonic mean was long, whereas the arithmetic mean interreinforcement
      interval of the second schedule was long, but the harmonic mean was short. The
      pigeons preferred the schedule with the shorter harmonic mean in a concurrent
      chains procedure when a terminal link ended after the first scheduled reinforcer
      had been gained on a terminal-link entry, but reversed their preferences, such
      that they preferred the schedule with the shorter arithmetic mean, when the
      terminal links ended after a fixed duration of exposure to the schedule.
      Moreover, the pigeons preferred the schedule with the shorter arithmetic mean in
      a two-key concurrent variable-interval variable-interval procedure, as well as in
      a concurrent variable-time variable-time, changeover-key procedure. The data
      suggest that an aggregate property of a schedule may not yield valid information
      about the responding that schedule will maintain as a choice alternative.

PMID- 16812393
TI  - Present trends and directions for the future (Introduction to Special Issue).

PMID- 16812394
TI  - Conceptual approaches and issues.
AB  - The experimental analysis of behavior has lagged far behind mainstream
      psychology, particularly cognitive psychology, in the study of complex behavior
      remembering, thinking, imaging, problem solving, and the like. Yet it is the
      study of these kinds of behavior that will provide the greatest justification of
      our continued existence in the community of behavioral scientists. Focusing
      primarily on remembering as a complex performance, aspects of (1) radical
      behaviorism, (2) the methodology of the experimental analysis of behavior, and
      (3) the special contributions of B. F. Skinner are assessed as explicitly or
      implicitly discouraging the experimental treatment of such complex behavior.
      Although there are encouraging signs of advancement into the present domains of
      cognitive psychology, future success of the experimental analysis of behavior in
      this endeavor will require aggressive pursuit by investigators and more effective
      training of their students.

PMID- 16812395
TI  - Verbal behavior.
AB  - THE RECENT HISTORY AND CURRENT STATUS OF THE AREA OF VERBAL BEHAVIOR ARE
      CONSIDERED IN TERMS OF THREE MAJOR THEMATIC LINES: the operant conditioning of
      adult verbal behavior, learning to be an effective speaker and listener, and
      developments directly related to Skinner's Verbal Behavior. Other topics not
      directly related to the main themes are also considered: the work of Kurt
      Salzinger, ape-language research, and human operant research related to rule
      governed behavior.

PMID- 16812396
TI  - Interpersonal relations: Cooperation and competition.
AB  - Social relations between two persons require that consequences each receives
      depend at least in part on the responses of the other. Historically, research in
      several areas has focused on two contingencies, cooperation and competition, in
      which reinforcement is determined by the responses of both participants. A major
      research question in social psychology and applied behavior analysis has been:
      Which contingency is more effective with regard to the quantity or quality of
      some response? Although this question has not been addressed in the experimental
      analysis of behavior, this area provides a perspective and method to more fully
      investigate the relevant controlling variables. Among these are the frequency of
      opportunities to audit the performances of others, information (or lack of it)
      provided by social or nonsocial stimuli with regard to reinforcement and
      performance, degree of face-to-face interaction, types of reinforcement
      contingencies, and number of participants. A neglected dependent variable is cost
      effectiveness-amount of behavior maintained by a given reinforcer amount. The
      larger agenda for the experimental analysis of interpersonal relations includes a
      variety of forms of reinforcement interdependence that raise issues of basic and
      applied interest.

PMID- 16812397
TI  - Experimental analysis of individual differences and personality.
AB  - IN PSYCHOLOGICAL STUDIES INDIVIDUAL DIFFERENCES THAT RESULT IN VARIABILITY IN
      DATA AND THUS MASK THE EFFECTS UNDER INVESTIGATION HAVE BEEN REDUCED OR
      ELIMINATED IN TWO WAYS: (1) through the use of large numbers of subjects and
      statistical manipulations, or (2) through extensive and controlled studies of
      individual subjects. The latter, behavior-analytic, method is scientifically
      better because it permits identification of the variables that result in
      individual differences. This paper advocates the direct study of individual
      differences and personality rather than indirect study through experimental
      control procedures. Some data are presented showing that individual differences
      in response patterns have orderly characteristics. Extension of the experimental
      analysis of behavior to the study of individual differences and personality is
      likely to be important both scientifically and for the future growth of behavior
      analysis.

PMID- 16812398
TI  - Melioration and self-experimentation.
AB  - Operant researchers rarely use the arena of applied psychology to motivate or to
      judge their research. Absence of tests by application weakens the field of basic
      operant research. Early in their development, the physical and biological
      sciences emphasized meliorative aspects of research. Improvement of human life
      was a major goal of these young sciences. This paper argues that if basic operant
      researchers analogously invoked a melioration criterion, the operant field might
      avoid its tendency toward ingrowth and instead generate a broadly influential
      science. Operant researchers could incorporate melioration by (a) creating animal
      models to study applied problems; (b) confronting questions raised by applied
      analysts and testing hypotheses in applied settings; or (c) performing self
      experiments-that is, using experimental methods and behavioral techniques to
      study and change the experimenter's behavior.

PMID- 16812399
TI  - Cognition, behavior, and the experimental analysis of behavior.
AB  - A case history illustrates how one research program in the experimental analysis
      of behavior evolved somewhat differently from the modal research program
      represented in this journal. A chief issue that seems to be responsible for this
      difference is the role attributed to theory in behavioral research: Skinner's
      views on the nature and function of theory and on the nature of observation
      combine to produce a certain kind of picture of behavior. The classic conception
      of reinforcement contingencies is tied to this particular picture. But this
      picture may be incompatible with, and certainly is different from, other possible
      pictures. Reinforcement contingencies that place greater emphasis on the local
      temporal patterning of behavior seem tied to some of these alternative pictures
      of what behavior is. These other pictures encourage a wide range of theoretical
      approaches, including cognitive ones, various kinds of mathematical analyses, and
      computer-simulation methods to characterize entire behavior streams. In the
      future, perhaps the experimental analysis of behavior will accept a somewhat
      different range of views on the nature and function of theory, a correspondingly
      different set of experimental methods, and alternative ways of talking about
      behavior.

PMID- 16812400
TI  - Quantitative analysis.
AB  - Quantitative analysis permits the isolation of invariant relations in the study
      of behavior. The parameters of these relations can serve as higher-order
      dependent variables in more extensive analyses. These points are illustrated by
      reference to quantitative descriptions of performance maintained by concurrent
      schedules, multiple schedules, and signal-detection procedures. Such quantitative
      descriptions of empirical data may be derived from mathematical theories, which
      in turn can lead to novel empirical analyses so long as their terms refer to
      behavioral and environmental events. Thus, quantitative analysis is an integral
      aspect of the experimental analysis of behavior.

PMID- 16812401
TI  - Behavioral economics.
AB  - Economics, like behavioral psychology, is a science of behavior, albeit highly
      organized human behavior. The value of economic concepts for behavioral
      psychology rests on (1) their empirical validity when tested in the laboratory
      with individual subjects and (2) their uniqueness when compared to established
      behavioral concepts. Several fundamental concepts are introduced and illustrated
      by reference to experimental data: open and closed economies, elastic and
      inelastic demand, and substitution versus complementarity. Changes in absolute
      response rate are analyzed in relation to elasticity and intensity of demand. The
      economic concepts of substitution and complementarity are related to traditional
      behavioral studies of choice and to the matching relation. The economic approach
      has many implications for the future of behavioral research and theory. In
      general, economic concepts are grounded on a dynamic view of reinforcement. The
      closed-economy methodology extends the generality of behavioral principles to
      situations in which response rate and obtained rate of reinforcement are
      interdependent. Analysis of results in terms of elasticity and intensity of
      demand promises to provide a more direct method for characterizing the effects of
      "motivational" variables. Future studies of choice should arrange heterogeneous
      reinforcers with varying elasticities, use closed economies, and modulate
      scarcity or income. The economic analysis can be extended to the study of
      performances that involve subtle discriminations or skilled movements that vary
      in accuracy or quality as opposed to rate or quantity, and thus permit
      examination of time/accuracy trade-offs.

PMID- 16812402
TI  - The operant-respondent distinction: Future directions.
AB  - The operant-respondent distinction has provided a major organizing framework for
      the data generated through the experimental analysis of behavior. Problems have
      been encountered, however, in using it as an explanatory concept for such
      phenomena as avoidance and conditioned suppression. Data now exist that do not
      fit neatly into the framework. Moreover, the discovery of autoshaping has
      highlighted difficulties in isolating the two types of behavior and conditioning.
      Despite these problems, the operant-respondent framework remains the most
      successful paradigm currently available for organizing behavioral data. Research
      and theoretical efforts should therefore probably be directed to modifying the
      framework to account for disparate data.

PMID- 16812403
TI  - The sleeping giant: Reinforcement schedules.
AB  - Schedule research has been the core of operant conditioning, but it is no longer
      an active area, at least with respect to its traditional focus of describing and
      explaining moment-to-moment behavior. Yet schedules are central in psychology:
      Not only do they establish lawful behavior, but they also play a major role in
      determining the effects of other variables. The reason for the decline appears to
      be primarily theoretical, in that the work seems not to have led to meaningful
      integration. The search for controlling variables brought into play by schedule
      specification has proven unsuccessful, and a catalog of all possible schedule
      effects is of limited interest. The paper reviews the reasons for the
      contemporary state of affairs. One prediction about future developments is that
      instead of revealing component variables and their modes of interaction, schedule
      effects will be treated as basic empirical laws. Theory will take the form of
      abstract statements that integrate these separate laws by reference to higher
      order principles rather than by reduction to supposedly simpler component
      variables.

PMID- 16812404
TI  - Aversive control: A separate domain?
AB  - Traditionally, aversive control has been viewed as a separate domain within
      behavior theory. Sometimes this separateness has been based upon a distinction
      between reinforcement and punishment, and sometimes upon a distinction between
      positive and negative reinforcement. The latter is regarded here as the more
      compelling basis, due to some inherent procedural asymmetries. An approach to the
      interpretation of negative reinforcement is presented, with indication of types
      of experiments that support it and that also point to promising directions for
      further work. However, most of the interpretive issues that arise here are
      relevant to positively reinforced behavior as well. These include: possible
      reformulation of the operant/respondent distinction; the place of emotional
      concepts in behavior analysis; the need for simultaneous, complementary analysis
      on differing time scales; the understanding of behavioral situations with
      rewarding or aversive properties that depend as much upon the contingencies that
      the situations involve as upon the primary rewarding or aversive stimuli that
      they include. Thus, an adequate understanding of this domain, which has been
      traditionally viewed as distinct, has implications for all domains of behavior
      analytic theory.

PMID- 16812405
TI  - Temporal patterns of responding in small fixed-ratio schedules.
AB  - Pigeons were exposed to an ascending series of small fixed-ratio schedules from
      fixed-ratio 1 to 7. Two of those pigeons were later placed on a fixed-ratio 30
      schedule. The two primary dependent variables were the postreinforcement pause
      and the interresponse time. Changes in these variables under small fixed ratios
      were sometimes opposite to changes reported with large fixed ratios. For example,
      postreinforcement pauses decreased in length as the fixed-ratio requirement
      increased from fixed-ratio 1 to fixed-ratio 3. Also, the interresponse times
      early in the small fixed-ratio schedule were shorter than those immediately
      preceding reinforcement. These findings question the role of interresponse-time
      reinforcement in determining temporal patterns of responding under small fixed
      ratio schedules. They also suggest that there may be a limited region in which
      the independent variable, fixed-ratio size, does not operate as previously
      described.

PMID- 16812406
TI  - Determination of a behavioral transfer function: White-noise analysis of session
      to-session response-ratio dynamics on concurrent VI VI schedules.
AB  - Six pigeons were exposed to concurrent variable-interval schedules in which the
      programmed reinforcer ratios changed from session to session according to a
      pseudorandom binary sequence. This procedure corresponded to the stochastic
      identification paradigm ("white-noise experiment") of systems theory and enabled
      the relation between log response ratios in the current session and log
      reinforcer ratios in all previous sessions to be determined. Such dynamic
      relations are called linear transfer functions. Both nonparametric and parametric
      representations of these, in the form of "impulse-response functions," were
      determined for each bird. The session-to-session response ratios resulting from
      the session-to-session pseudorandom binary variations in reinforcer ratios were
      well predicted by the impulse-response functions identified for each pigeon. The
      impulse-response functions were well fitted by a second-order dynamic model
      involving only two parameters: a time constant and a gain. The mean time constant
      was 0.67 sessions, implying that the effects of abrupt changes in log reinforcer
      ratios should be 96% complete within about five sessions. The mean gain was 0.53,
      which was surprisingly low inasmuch as it should equal the sensitivity to
      reinforcement ratio observed under steady-state conditions. The same six pigeons
      were subjected to a similar experiment 10 months following the first. Despite
      individual differences in impulse-response functions between birds within each
      experiment, the impulse-response functions determined from the two experiments
      were essentially the same.

PMID- 16812407
TI  - The functional independence of mands and tacts.
AB  - This study demonstrates functional independence in the acquisition of mands and
      tacts. Some subjects first learned to mand the experimenter's placement of
      objects with the prepositional phrases "On the left" and "On the right." They
      were regularly tested for collateral appearance of tacts with these same phrases.
      Other subjects learned to tact the location of objects with these prepositional
      phrases and were regularly tested for collateral appearance of mands. All
      subjects were next trained in the repertoire that had not been trained in the
      first condition (either tact or mand). After all subjects had learned both to
      mand and to tact correctly, another assessment of mand-tact independence was
      undertaken. Mands (tacts) were reversed and testing assessed collateral reversal
      of tacts (mands). The results demonstrated that tacts and mands, even when
      incorporating identical response forms, were functionally independent during
      acquisition. Subsequent modification of one repertoire (by reversal training)
      produced collateral reversal in three of nine subjects.

PMID- 16812408
TI  - Confirmation of linear system theory prediction: Rate of change of Herrnstein's
      kappa as a function of response-force requirement.
AB  - Four human subjects worked on all combinations of five variable-interval
      schedules and five reinforcer magnitudes ( cent/reinforcer) in each of two phases
      of the experiment. In one phase the force requirement on the operandum was low (1
      or 11 N) and in the other it was high (25 or 146 N). Estimates of Herrnstein's
      kappa were obtained at each reinforcer magnitude. The results were: (1) response
      rate was more sensitive to changes in reinforcement rate at the high than at the
      low force requirement, (2) kappa increased from the beginning to the end of the
      magnitude range for all subjects at both force requirements, (3) the reciprocal
      of kappa was a linear function of the reciprocal of reinforcer magnitude for
      seven of the eight data sets, and (4) the rate of change of kappa was greater at
      the high than at the low force requirement by an order of magnitude or more. The
      second and third findings confirm predictions made by linear system theory, and
      replicate the results of an earlier experiment (McDowell & Wood, 1984). The
      fourth finding confirms a further prediction of the theory and supports the
      theory's interpretation of conflicting data on the constancy of Herrnstein's
      kappa.

PMID- 16812409
TI  - Molecular maximizing characterizes choice on Vaughan's (1981) procedure.
AB  - Pigeons keypecked on a two-key procedure in which their choice ratios during one
      time period determined the reinforcement rates assigned to each key during the
      next period (Vaughan, 1981). During each of four phases, which differed in the
      reinforcement rates they provided for different choice ratios, the duration of
      these periods was four minutes, duplicating one condition from Vaughan's study.
      During the other four phases, these periods lasted six seconds. When these
      periods were long, the results were similar to Vaughan's and appeared compatible
      with melioration theory. But when these periods were short, the data were
      consistent with molecular maximizing (see Silberberg & Ziriax, 1982) and were
      incompatible with melioration, molar maximizing, and matching. In a simulation,
      stat birds following a molecular-maximizing algorithm responded on the short- and
      long-period conditions of this experiment. When the time periods lasted four
      minutes, the results were similar to Vaughan's and to the results of the four
      minute conditions of this study; when the time periods lasted six seconds, the
      choice data were similar to the data from real subjects for the six-second
      conditions. Thus, a molecular-maximizing response rule generated choice data
      comparable to those from the short- and long-period conditions of this
      experiment. These data show that, among extant accounts, choice on the Vaughan
      procedure is most compatible with molecular maximizing.

PMID- 16812410
TI  - Levels of aggregation: Relative time allocation in concurrent-schedule
      performance.
AB  - The proportion of time allocated to one component of a concurrent variable
      interval variable-interval schedule was computed for groups of interchangeover
      times (aggregates) within several intact time series. Variability in obtained
      proportions decreased as the number of interchangeover times within each
      aggregate increased; however, modal proportions failed to correspond to overall
      relative time allocation computed over the course of an entire experimental
      session, even at the largest aggregate size. The aggregated time series showed
      periodicities at small aggregate sizes and general trends in local preference at
      larger aggregate sizes. It is suggested that overall relative time allocation
      represents a molar extreme in the aggregation of behavior that may not accurately
      reflect central tendency in the allocation of time to available alternatives
      within the context of ongoing behavior.

PMID- 16812411
TI  - Effects of uninstructed verbal behavior on nonverbal responding: Contingency
      descriptions versus performance descriptions.
AB  - Undergraduates' button presses occasionally made available points that were
      exchangeable for money. Lights over left and right buttons were respectively
      correlated with multiple random-ratio random-interval components. During
      interruptions of the multiple schedule, students filled out sentence-completion
      guess sheets. When shaping of these guesses produced performance descriptions
      (e.g., "press slowly" for the left button and "press fast" for the right), button
      pressing rates typically were consistent with the verbal behavior even when rates
      were opposite to those ordinarily maintained by the respective schedules. When
      shaping instead produced contingency descriptions (e.g., the button works "after
      a random number of presses" or "a random time since it worked before"), pressing
      rates were inconsistently related to the descriptions; for some students
      descriptions of ratio contingencies generated higher corresponding pressing rates
      than were produced by descriptions of interval contingencies, but for others
      contingency descriptions and pressing rates were unrelated.

PMID- 16812412
TI  - The role of verbal behavior in human learning: II. Developmental differences.
AB  - When children in four different age ranges operated a response device,
      reinforcers were presented according to fixed-interval schedules ranging in value
      from 10 to 70 seconds. Only the behavior of the subjects in the youngest of the
      four groups, the preverbal infants, resembled that of other animal species. The
      children in age ranges 5 to 6(1/2) and 7(1/2) to 9 years exhibited either the low
      rate or high-rate response patterns typical of human adults. Those who showed the
      low-rate pattern reported a time-based formulation of the contingencies and some
      of them were observed to occasionally count out the interval before responding.
      The performance of children aged 2(1/2) to 4 years differed from that of both
      infants and older children, though containing some patterning elements similar to
      those produced by the older and younger subjects. The predominant response
      pattern of the infants consisted of a pause after reinforcement followed by an
      accelerated rate of responding that terminated when the next reinforcer was
      delivered. Analysis of postreinforcement-pause duration and response rate showed
      that infant performance, but not that of the older children, consistently
      exhibited the same kinds of schedule sensitivity observed in animal behavior. The
      evidence supports the suggestion that the development of verbal behavior greatly
      alters human operant performance and may account for many of the differences
      found between human and animal learning.

PMID- 16812413
TI  - Variation in Herrnstein's r(o) as a function of alternative reinforcement rate.
AB  - In a test of Herrnstein's (1970, 1974) equation for simple schedules, 15 pigeons
      pecked a key that produced food delivered according to variable-interval
      schedules. One group of birds was water deprived, and food-reinforced key pecking
      occurred in the presence of free water. Two other groups were not water deprived;
      water was present for one and absent for the other. As predicted by Herrnstein,
      the parameter r(o) was significantly higher in the water-deprived group than in
      the two nondeprived groups. Contrary to Herrnstein's interpretation of r(o), the
      rate of drinking varied across schedules. Herrnstein's interpretation can be
      salvaged by considering r(o) to be an average. However, if r(o) is an average,
      the equation is not a good explanation of behavior because this average is not
      valid until all schedules have been sampled. In addition, low percentages of
      variance accounted for suggest that Herrnstein's equation may be of limited
      usefulness even as a descriptive model for these situations.

PMID- 16812414
TI  - Effects of ratio reinforcement schedules on discrimination performance by
      Japanese monkeys.
AB  - In Experiment 1, Japanese monkeys were trained on three conditional position
      discrimination problems with colors as the conditional cues. Within each session,
      each problem was presented for two blocks of ten reinforcements; correct
      responses were reinforced under continuous-reinforcement, fixed-ratio 5, and
      variable-ratio 5 schedules, each assigned to one of the three problems. The
      assignment of schedules to problems was rotated a total of three times (15
      sessions per assignment) after 30 sessions of acquisition training. Accuracy of
      discrimination increased to a moderate level with fewer trials under CRF than
      under ratio schedules. In contrast, the two ratio schedules, fixed and variable,
      were more effective in maintaining accurate discrimination than was CRF. With
      further training, as asymptotes were reached, accuracy was less affected by the
      schedule differences. These results demonstrated an interaction between the
      effects of reinforcement schedules and the level of acquisition. In Experiment 2,
      ratio sizes were gradually increased to 30. Discrimination accuracy was
      maintained until the ratio reached 20; ratio 30 strained the performance. Under
      FR conditions, accuracy increased as correct choice responses cumulated after
      reinforcement.

PMID- 16812415
TI  - Reinforcement of probe responses and acquisition of stimulus control in fading
      procedures.
AB  - Stimulus control of pigeons' key pecking was transferred from colors to lines by
      the method of stimulus fading. Fading was conducted with the addition of probes
      consisting of the line stimuli presented alone at each fading level. Probe
      responding was used to measure stimulus-control acquisition by the lines. Effects
      of reinforcement and nonreinforcement of probe responding upon acquisition of
      stimulus control were assessed using a single-organism repeated-acquisition
      design in which three fades were conducted serially. Probe responding was not
      reinforced in the first and third fade but was in the second. Reinforcement of
      probe responding substantially reduced the number of fading levels needed to
      complete fading. The outcome of a control experiment ruled out the possibility of
      accounting for these results in terms of the specific stimuli used in each fade
      or in terms of the sequential exposure to the three discriminations. Although
      probes permitted measurement of stimulus-control acquisition in fading, a
      measurement/acquisition interaction was also present.

PMID- 16812416
TI  - Reanalysis of the equation for simple action.
AB  - De Villiers and Herrnstein (1976) have shown that the equation for simple action,
      derived from the matching law, predicts change in behavioral output for some 40
      experiments in which the value of a single source of reinforcement has been
      varied. Using only the positive-reinforcement studies they cite that used five or
      more different reinforcement values, we found the high percentage of variance
      they report accommodated by this equation (94%) is predicated on instances of
      averaging rates of behavioral output before making a least-squares fit of the
      equation. In our reanalysis, which minimizes rate averaging, only 78% of the data
      variance is accommodated. This diminished data-variance accommodation can be
      improved by adding parameters that permit the equation's scaling constant to
      change as a function of reinforcement. Although these parameters permit
      acceptable levels of accommodation of data variance, they correspond to no
      obvious psychological processes. These findings support the view that the
      equation for simple action is an inadequate model for behavioral output.

PMID- 16812417
TI  - Verbal relations within instruction: Are there subclasses of the intraverbal?
AB  - Six college undergraduates received programmed concept training on three kinds of
      intraverbal relations. These relations involved definition, exemplification, and
      example identification questions. The experimenter presented the questions, the
      subject answered them in writing, and the experimenter provided specific
      corrective consequences. After completing the training on a concept, the subject
      immediately received a test on the concept. The test included novel questions
      similar to the kind used in training (extension tasks) and question types that
      were not used in training but which were also considered intraverbal relations
      (transfer tasks). Training results indicated rapid, errorful responding on
      example identification tasks and slow, accurate responding on exemplification and
      definition tasks. Test results indicated rapid, errorful responding on example
      identification extension tasks; slow, accurate responding on exemplification
      extension tasks; and slow, errorful responding on definition extension tasks. In
      testing, differential responding occurred on transfer tasks as a function of the
      kind of intraverbal training received, and substantially lower levels of
      performance were obtained on transfer tasks than on extension tasks. It appears
      that the intraverbal can be subdivided into more specific categories of operants.

PMID- 16812418
TI  - Sign-tracking with an interfood clock.
AB  - Food was presented to pigeons, irrespective of their behavior. The fixed 60-s
      interfood interval was segmented into ten 6-s periods, each signaled by a
      distinctive stimulus color, ordered by wavelength. This "interfood clock"
      reliably generated and maintained successively higher rates of key pecking at
      stimuli successively closer to food. Under extinction, key pecking ceased. When
      the standard stimulus sequence was changed to a different sequence for each bird,
      accelerated responding again emerged and was sustained under each of the new
      color sequences. However, responding was neither maintained nor acquired when
      each successive interfood interval provided a different random sequence of the
      ten stimuli. Thus, the interfood clock generated and maintained sign-tracking
      under stimulus control, and the resulting behavior was attributable neither to
      stimulus generalization nor to a simple temporal gradient.

PMID- 16812419
TI  - Interresponse-time analysis of stimulus control in multiple schedules.
AB  - Interresponse-time distributions were recorded in two components of multiple
      variable-interval schedules that were varied over several conditions. Values of
      the exponent for power functions relating ratios of interresponse times emitted
      per opportunity to ratios of reinforcers obtained in the two components varied
      with interresponse-time class interval. The exponent (sensitivity to
      reinforcement) afforded a measure of stimulus control exerted by the
      discriminative stimuli. Exponents were near zero for short interresponse times,
      consistent with previous conclusions that responses following short interresponse
      times are controlled by response-produced or proprioceptive stimuli. Values of
      exponents increased with longer interresponse times, indicating strong control by
      exteroceptive stimuli over responses following interresponse times of
      approximately one second or longer.

PMID- 16812420
TI  - Choice: A local analysis.
AB  - Analyses of free-operant choice usually employ one of two general procedures: the
      simple concurrent procedure (i.e., a concurrent variable-interval variable
      interval schedule) or the concurrent-chains procedure (i.e., concurrently
      available initial links, each leading to an exclusively available terminal link).
      Theories about choice usually focus on only one of the two procedures. For
      example, maximization theories, which assert that behavior is distributed between
      two alternatives in such a way that overall rate of reinforcement is maximized,
      have been applied only to the simple concurrent procedure. In the present paper,
      a form of the pairing hypothesis (according to which pairings between one
      stimulus and another affect the value of the first, and pairings between
      responses and reinforcers affect the value of the former) is developed in a way
      that allows it to make qualitative predictions with regard to choice in a variety
      of simple concurrent and concurrent-chains procedures. The predictions include
      matching on concurrent variable-interval variable-interval schedules, preference
      reversal in the self-control paradigm, and preference for tandem over chained
      terminal links.

PMID- 16812421
TI  - Incentive theory: IV. Magnitude of reward.
AB  - Incentive theory is successfully applied to data from experiments in which the
      amount of food reward is varied. This is accomplished by assuming that incentive
      value is a negatively accelerated function of reward duration. The interaction of
      the magnitude of a reward with its delay is confirmed, and the causes and
      implications of this interaction are discussed.

PMID- 16812422
TI  - Component probability and component reinforcer rate as biasers of free-operant
      detection.
AB  - Six pigeons were trained on multiple schedules whose components were concurrent
      variable-interval extinction and concurrent extinction variable-interval
      schedules. In Experiments 1a and 1b the stimuli signaling the components were two
      different light intensities, and in Experiments 2a and 2b they were two identical
      intensities. The components of the multiple schedule changed probabilistically
      after each reinforcer. In Experiments 1a and 2a, the probability of presenting
      the components was varied over five conditions and a replication. In Experiments
      1b and 2b, the component probability was .5 and the component reinforcer rates
      were varied systematically over five conditions and a replication. The data,
      analyzed according to the Davison-Tustin behavioral detection model, confirmed
      that the discriminability of the stimuli signaling the components was high when
      the stimuli were different, and low when the stimuli were the same.
      Discriminability, measured by log d, was unaffected by component probability
      variation and by component reinforcer-rate variation. When discriminability was
      high, bias, or the response allocation between the two keys, was more strongly
      affected by variation of reinforcer rate within components than by variation of
      component probability, but the reverse was found when discriminability was low.
      The results suggest that free-operant detection performance is controlled by the
      rates of reinforcers in periods of time in which stimuli signal differential
      contingencies. These periods comprise the components when the component stimuli
      are discriminable, and comprise the total session when the components are
      indiscriminable. An extension of the Davison-Tustin behavioral detection model
      that incorporates these results is presented.

PMID- 16812423
TI  - An inexpensive 10-digit printout counter.

PMID- 16812424
TI  - Characteristics of forgetting functions in delayed matching to sample.
AB  - Performance of pigeons in delayed matching-to-sample procedures was measured in
      terms of an index of discriminability derived from the difference between
      logarithms of ratios of choice responses to comparison stimuli following the
      different sample stimuli. Forgetting functions that plotted discriminability as a
      function of delay-interval duration were well described by a simple negative
      exponential function with two parameters, one describing initial discriminability
      of sample stimuli at zero delay (log d(0)) and the other describing rate of
      decrement in discriminability with increasing delay-interval duration (b). With
      the difference between wavelength values of the comparison stimuli held constant,
      a large difference between wavelengths of the sample stimuli resulted in a higher
      log d(0) value than that for a small difference between sample stimuli, without
      changing the rate of decrement in discriminability, b. An increase in the fixed
      ratio requirement for sample-key responding produced an increase in log d(0)
      without affecting b, and interpolation of ambient illumination in the delay
      interval increased b without influencing log d(0). Both parameters changed when
      intertrial-interval duration was varied. The result of variation in the point of
      interpolation of ambient illumination in the delay interval indicated that levels
      of discriminability at longer delays were independent of discriminability levels
      at earlier delays, consistent with the properties of the exponential function.
      Functions relating performance to delay-interval duration were suggested to have
      two characteristics: discriminability of the sample stimuli in the absence of a
      delay between the stimuli and the behavior they occasion, and rate of attenuation
      in discriminability with increasing delay-interval duration.

PMID- 16812425
TI  - Symmetry and transitivity of conditional relations in monkeys (Cebus apella) and
      pigeons (Columba livia).
AB  - In Experiment 1 six monkeys were tested with discriminative relations that were
      backward relative to their training in a 0-second conditional ("symbolic")
      matching procedure. Although there was some indication of backward associations,
      the evidence was generally weak, and statistical evaluations did not reach
      conventional significance levels. Unlike children, who show backward associations
      to the point of symmetry, monkeys and pigeons display at best only weak and
      transient backward associations. In Experiment 2 associative transitivity was
      assessed across two sets of conditional matching tasks. All four monkeys tested
      demonstrated strong transitivity. In contrast, in Experiment 3 there was no
      evidence of transitivity in three pigeons tested under conditions closely
      comparable to those of Experiment 2. These results may identify some key features
      of interspecies differences and contribute to analyses of serial learning in
      animals.

PMID- 16812426
TI  - Contributions of elicitation to measures of self-control.
AB  - Pigeons' not pecking or pecking constituted choice between a delayed, large
      reinforcer and an immediate, small reinforcer (self-control) and at other times
      between a delayed reinforcer and no reinforcer (omission). Both a tone and a
      keylight were tested as choice signals, and the delayed reinforcer was either
      response independent or response dependent. Pigeons pecked during the choice
      signals on over 95% of the trials in the self-control procedure, and pecked
      during the choice signals on over 75% of the trials in the omission procedure.
      Consistent pecking was observed with either the tone or the keylight as a choice
      signal, with the exception that a tone paired with a response-independent delayed
      reinforcer did not maintain pecking in the omission procedure. Pigeons pecked
      during more choice signals when delayed reinforcers were response dependent than
      when the delayed reinforcers were response independent. These results indicate
      that Pavlovian conditioning influences self-control experiments, especially in
      single-key procedures.

PMID- 16812427
TI  - Sensitivity of time allocation to concurrent-schedule reinforcement.
AB  - Four pigeons were trained on concurrent variable-interval schedules programmed on
      a center response key, with access to those schedules controlled by responses on
      left or right side keys. Two procedures were used. In one, the pigeon was given
      limited access, in that each side-key response produced 3-s access to a center
      key schedule, and in the other procedure, access was unlimited. Data were
      analyzed using the generalized matching law. Comparison of sensitivities to
      reinforcement of interchangeover time for both procedures showed them to be of
      similar magnitude. Response sensitivities were also similar in magnitude for both
      procedures. From the limited-access procedure a second time measure that was
      available, switched-in time, was relatively uncontaminated by time spent emitting
      behavior other than key pecking. Sensitivities to reinforcement for the switched
      in time measure were always smaller than interchangeover-time sensitivities for
      either procedure, and were approximately equal to response sensitivities for the
      limited-access procedure. Two other access times (5 and 7.5 s) were studied to
      validate the choice of 3 s as the main access time. These results indicate that
      when time spent emitting other behavior is excluded from interchangeover time,
      time and response sensitivities will be approximately equal.

PMID- 16812428
TI  - Preference for unsegmented interreinforcement intervals in concurrent chains.
AB  - Five pigeons were trained under concurrent-chain schedules in which a pair of
      independent, concurrent variable-interval 60-s schedules were presented in the
      initial link and either both variable-interval or both fixed-interval schedules
      were presented in the terminal link. Except for the baseline, one of the terminal
      link schedules was always a two-component chained schedule and the other was
      either a simple or a tandem schedule of equal mean interreinforcement interval.
      The values of the fixed-interval schedules were either 15 s or 60 s; that of the
      variable-interval schedules was always 60 s. A 1.5-s changeover delay operated
      during the initial link in some conditions. The pigeons preferred a simple or a
      tandem schedule to a chain. For the fixed-interval schedules, this preference was
      greater when the fixed interval was 60 s than when it was 15 s. For the variable
      interval schedules, the preferences were less pronounced and occurred only when
      the changeover delay was in effect. For a given type of schedule and
      interreinforcement interval, similar preferences were obtained whether the
      nonchained schedule was a tandem or simple schedule. The changeover delay
      generally inflated preference and lowered the changeover rate, especially when
      the terminal-link schedules were either short (15 s) or aperiodic (variable
      interval). The results were consistent with the notion that segmenting the
      interreinforcement interval of a schedule into a chain lowers the preference for
      it.

PMID- 16812429
TI  - Handling time and choice in pigeons.
AB  - According to optimal foraging theory, animals should prefer food items with the
      highest ratios of energy intake to handling time. When single items have
      negligible handling times, one large item should be preferred to a collection of
      small ones of equivalent total weight. However, when pigeons were offered such a
      choice on equal concurrent variable-interval schedules in a shuttlebox, they
      preferred the side offering many small items per reinforcement to that offering
      one or a few relatively large items. This preference was still evident on
      concurrent fixed-cumulative-duration schedules in which choosing the alternative
      with longer handling time substantially lowered the rate of food intake.

PMID- 16812430
TI  - Repeated acquisition in the analysis of rule-governed behavior.
AB  - Five children, ranging in age from 3(1/2) years to 5(1/2) years, were taught
      various four-response chains using conditioned reinforcement. Experiment 1
      investigated the effects of presenting "instruction" stimuli-a sequence of lights
      over the correct response buttons-to assess their role in facilitating the
      acquisition of a chain of responses. Without the "instruction" stimuli, children
      made many errors before responses were brought under the control of the
      programmed contingencies. When confronted with the same contingencies later in
      the day, these subjects made fewer errors. In contrast, in the presence of the
      "instruction" stimuli, subjects made virtually no errors. However, when the
      "instruction" stimuli were discontinued in the subsequent session, all 5 subjects
      made errors. In Experiment 2, the subjects were taught to verbalize the
      contingencies during the phase without the "instruction" stimuli. This resulted
      in errorless performance during the subsequent exposure to the same procedure,
      but errors nevertheless occurred again during reexposure to the procedure with
      the "instruction" stimuli discontinued.

PMID- 16812431
TI  - Temporal proximity and reinforcement sensitivity in multiple schedules.
AB  - Distributions of reinforcers between two components of multiple variable-interval
      schedules were varied over a number of conditions. Sensitivity to reinforcement,
      measured by the exponent of the power function relating ratios of responses in
      the two components to ratios of reinforcers obtained in the components, did not
      differ between conditions with 15-s or 60-s component durations. The failure to
      demonstrate the "short-component effect," where sensitivity is high for short
      components, was consistent with reanalysis of previous data. With 60-s
      components, sensitivity to reinforcement decreased systematically with time since
      component alternation, and was higher in the first 15-s subinterval of the 60-s
      component than for the component whose total duration was 15 s. Varying component
      duration and sampling behavior at different times since component transition may
      not be equivalent ways of examining the effects of average temporal distance
      between components.

PMID- 16812432
TI  - Spatiotemporal patterns of behavior produced by variable-interval schedules of
      reinforcement.
AB  - The spatiotemporal patterns of behavior exhibited by two pigeons during a
      variable-interval 15-second schedule of food reinforcement, a variable-interval 5
      minute schedule, and then extinction of key pecking were recorded using an
      apparatus that continuously tracked the position of the bird in the experimental
      chamber. The variable-interval 15-second schedule produced a close-to-key pattern
      between reinforcements with two types of regular excursions from the region of
      the key frequently occurring after reinforcement. Subsequent exposure to the
      variable-interval 5-minute schedule produced more extended and extremely regular
      patterns between responses. Reinstatement of the variable-interval 15-second
      schedule reestablished the close-to-key pattern with regular excursions
      frequently occurring after reinforcement. During extinction the spatiotemporal
      patterns that had developed during the variable-interval 5-minute schedule
      reappeared and gradually dissipated. These patterns may have been a form of
      superstitious behavior.

PMID- 16812433
TI  - Sequential effects in dimensional contrast.
AB  - Two experiments examined pigeons' response rates during short trials signaled by
      stimuli closely spaced along a wavelength continuum. In Experiment 1 separate
      halves of the continuum were correlated with different reinforcement schedules.
      In Experiment 2, the middle stimulus was accompanied by a lower probability of
      reinforcement than were the remaining wavelengths. Both procedures resulted in
      dimensional contrast "shoulders," seen as relatively enhanced or depressed
      response rates in the presence of stimuli between the extreme of the continuum
      and the border separating the positive and negative stimuli. Sequential analyses
      addressed possible contributions of the following interactions: (a) local
      contrast, seen when rate during a given schedule depends on the schedule in the
      just-preceding trial; (b) modification of local contrast by the similarity of the
      signaling stimuli (P. Blough, 1983); and (c) schedule-independent rate contrast,
      seen when rate in a given trial depends on the rate controlled by the stimulus
      that accompanied the just-preceding trial (Malone & Rowe, 1981). Dimensional
      contrast functions were similar when isolated according to the schedule, to the
      similarity of the signaling stimulus, and to the response rate of the just
      preceding trial. The interactions noted above do not appear to make important
      contributions to this effect.

PMID- 16812434
TI  - Local temporal pattering of operant behavior in humans.
AB  - Button pressing by 44 college students intermittently produced points and the
      words "GOOD" or "POOR" on a computer screen. The events were arranged according
      to a paced random-interval 10-s schedule in which the target interresponse-time
      categories were 1 to 3, 3 to 5, or 6 to 12 s. The degree to which instructions
      specified certain aspects of the contingency (e.g., whether response spacing was
      critical) was also varied, and in some conditions the experimenter prompted
      specifically paced responses during the first 2 min of the session. The
      procedures shaped the local patterning of behavior of some subjects in less than
      30 min of exposure to the contingencies. Most subjects who, in a postexperimental
      questionnaire, accurately identified the schedule contingencies also responded
      more accurately than those whose verbal descriptions were inaccurate or
      imprecise.

PMID- 16812435
TI  - Some parameters of behavioral contrast and allocation of interim behavior in
      rats.
AB  - Two experiments examined the effects of baseline reinforcement rate and component
      duration on behavioral contrast and on re-allocation of interim behavior in rats.
      Positive behavioral contrast occurred during multiple variable-interval 10-second
      extinction (VI 10 EXT) after a multiple VI 10 VI 10 baseline condition, but not
      during multiple VI 60 EXT following multiple VI 60 VI 60 baseline. Component
      duration had no significant effect on contrast. These results differed from those
      found in studies of pigeons' key pecking. Contrast was accompanied by an
      increased rate of drinking in the changed component, but drinking in the constant
      component did not decrease. These results are not consistent with the competition
      theory of contrast, but are consistent with the predictions based on the matching
      law. However, no current theory seems to account for all instances of behavioral
      contrast.

PMID- 16812436
TI  - Homogeneous chains, heterogeneous chains, and delay of reinforcement.
AB  - Three pigeons responded on two-component chain schedules in which the required
      response topography in the initial and terminal links was similar (a homogeneous
      chain) or dissimilar (a heterogeneous chain). Key-peck responding in the initial
      link under a variable-interval 60-second (VI 60) schedule produced a terminal
      link in which, in different conditions, either key pecking or foot treadling was
      reinforced according to a VI 60 schedule. Multiple VI 60 VI 60 schedules, in
      which the responses required in the chain schedules were maintained by primary
      reinforcement in the two components, preceded and followed each type of chain.
      These multiple schedules were used to ensure that both responses occurred
      reliably prior to introducing the chain schedule. Key-peck response rates in the
      initial link of the chain consistently were higher during the homogeneous chain
      than during the heterogeneous chain. These results illustrate that intervening
      events during a period separating an operant response from primary reinforcement
      influence that operant, independently of the delay between the response and
      reinforcement.

PMID- 16812437
TI  - Performance in continuously available multiple schedules.
AB  - Three pigeons were given continuous access in their home cages to food
      reinforcement on two-component multiple variable-interval variable-interval
      schedules. The reinforcer rates in the two components were varied over seven
      experimental conditions, and a partial replication over five conditions was
      arranged one year later. When component reinforcer rates were unequal, ratios of
      component response rates were more extreme than ratios of obtained component
      reinforcer rates, a result which in a generalized-matching analysis is termed
      overmatching. This finding contrasts sharply with results obtained when multiple
      schedules are arranged in shorter sessions, in which performance is characterized
      by undermatching when subjects are deprived of food, and by matching, or equality
      between component response- and reinforcer-rate ratios, when deprivation is
      minimal. More molecular data obtained in two subsequent conditions suggested that
      this finding did not reflect local fluctuations or asymmetries in deprivation.
      Theories of multiple-schedule performance that predict that matching cannot be
      exceeded are disconfirmed by the present results.

PMID- 16812438
TI  - Selective punishment of interresponse times: The roles of shock intensity and
      scheduling.
AB  - Two experiments investigated the roles of shock intensity and scheduling in
      selective punishment of interresponse times. In each experiment the punishment
      contingencies were imposed on a background of rats' responding maintained by a
      variable-interval schedule of food presentation. In Experiment 1 all
      interresponse times greater than 8 seconds produced shock. In Experiment 2 all
      interresponse times greater than 8 seconds but less than 12 seconds produced
      shock. In each experiment shock intensity was initially 0.3 milliamperes (mA) and
      then was varied through an ascending sequence ranging from 0.1 mA to 0.4 mA, in
      0.1-mA increments. Experiment 1 produced response-rate increases at low
      intensities (0.1 and 0.2 mA) but eliminated responding at the remaining
      intensities. Experiment 2 produced response-rate increases only with 0.1-mA
      shock, although responding was maintained at all shock parameters investigated.
      Analysis of the interresponse times per opportunity showed differential
      suppression of the targeted responses in all cases except the high-intensity
      shock phases of Experiment 1. The current data support and extend previous
      studies of selective interresponse-time-dependent shock schedules but suggest
      that response-rate increases are not a necessary outcome of this type of
      procedure. The view that variable-interval schedules of shock presentation
      selectively target long interresponse times was also supported.

PMID- 16812439
TI  - Reinforcement probability and ordinal position of response in fixed-interval
      schedules.
AB  - Four rats pressed levers and received food pellets under fixed-interval
      reinforcement schedules of 20, 60, and 180 seconds. The number of responses in
      each interval was recorded. From these data, the probability of reinforcement was
      determined as a function of response count. These functions were generally
      increasing. This finding is consistent with previous suggestions that increasing
      response rates within fixed intervals may be a function of response count in
      addition to or instead of elapsed or remaining time.

PMID- 16812440
TI  - The evolution of verbal behavior.

PMID- 16812441
TI  - The matching law applies to wagtails' foraging in the wild.
AB  - Field data concerning the time budgets and foraging success of pied wagtails
      (Motacilla alba yarrelli, Gould) are reanalyzed. It is found that the data are
      well described by the generalized matching law, with a marked bias towards
      spending time on the territory. In this case matching is not the result of
      maximizing reward rate, but it remains possible that it results from an
      allocation of time that maximizes survival.

PMID- 16812442
TI  - Preference for multiple versus mixed schedules of reinforcement.
AB  - Five pigeons were trained in a concurrent-chain procedure. In the initial links,
      equal nonindependent variable-interval schedules were available concurrently on
      two keys. Completing the schedule on either key led to exclusive presentation of
      one of two further variable-interval schedules for a fixed period of time. During
      these terminal links, as many reinforcers as were scheduled could be obtained. If
      the response producing this terminal link occurred on one key, differential
      stimuli signaled which variable-interval schedule had been produced. If the
      response producing the terminal link occurred on the other key, no such
      differential stimuli were available. Once the fixed period of time elapsed, the
      initial links were reinstated. In Experiment 1, the period of time for which the
      terminal links were available was always 10 s and the absolute duration of the
      initial links was varied. Subjects preferred the alternative leading to the
      multiple schedule when the initial-link duration was short, but preferred the
      alternative leading to the mixed schedule when the initial-link durations were
      longer. In Experiment 2, both the initial-link duration and the duration of the
      terminal links were varied. The effect of initial-link duration was identical to
      that in Experiment 1 and there was no systematic effect of varying the terminal
      link duration.

PMID- 16812443
TI  - The temporal pattern of unconstrained drinking: Rats' responses to inversion and
      identity constraints.
AB  - Rats obtained all of their water by licking a metal tube during a series of daily
      1-hour sessions. When the tube was freely available throughout, each rat showed
      the classic temporal pattern of unconstrained drinking: As the session
      progressed, drinking bouts generally grew shorter and pauses grew longer. In
      subsequent sessions the tube was opened and closed independently of the rat's
      behavior, on a schedule that gave the rat a chance to duplicate the exact inverse
      of its unconstrained baseline pattern. Thus, as the inversion session progressed,
      the opportunities to drink generally grew longer and the enforced pauses grew
      shorter. When the rats were forced away from their unconstrained patterns of
      drinking and pausing, their total time spent drinking consistently fell short of
      previous values, but total licks and volumetric intake remained at previous
      levels. The same results occurred under an identity schedule, a series of
      openings and closings that duplicated the unconstrained pattern of drinking and
      pausing. The results have implications for theories that assume that instrumental
      performance under schedule constraint derives from the animal's defense of a
      measured set-point.

PMID- 16812444
TI  - Superimposition of response-independent reinforcement.
AB  - Studies that have superimposed response-independent reinforcement (or reinforcers
      scheduled by contingencies placed on the absence of responding) upon conventional
      response-dependent schedules are reviewed. In general, providing alternative
      sources of reinforcement reduced response rates below the levels observed when
      alternative reinforcement was absent. However, response-rate elevation was
      sometimes found, particularly when rates of superimposed response-independent
      reinforcement were low. Superimposition of schedules providing reinforcers
      contingent on the absence of responding usually produced more severe response
      rate decrements than superimposition of response-independent reinforcement. A
      variant of Herrnstein's equation, which assumes that some of the alternative
      reinforcers function as if they were delivered by baseline response-dependent
      source of reinforcement, is in qualitative agreement with the overall body of
      results obtained, and can predict both increases and decreases in response rate
      as resulting from superimposed reinforcers.

PMID- 16812445
TI  - The generalized matching law as a description of multiple-schedule responding.
AB  - The literature was examined to determine how well the generalized matching law
      (Baum, 1974) describes multiple-schedule responding. In general, it describes the
      data well, accounting for a median of 91% of the variance. The median size of the
      undermatching parameter was 0.46; the median bias parameter was 1.00. The size of
      the undermatching parameter, and the proportion of the variance accounted for by
      the equation, varied inversely with the number of schedules conducted, with the
      number of sessions conducted per schedule, and with the time within a component.
      The undermatching parameter also varied with the operanda used to produce
      reinforcers and with the reinforcer used. The undermatching parameter did not
      vary consistently with component duration or with several other variables. Bias
      was greater when fewer rather than more schedules were conducted, when two rather
      than one operanda were used, and when White Carneaux rather than homing pigeons
      served as subjects. These results imply that the generalized matching law may
      describe both concurrent and multiple-schedule responding, but that the same
      variables do not always influence the bias and undermatching parameters in the
      same way for the two types of schedules.

PMID- 16812447
TI  - Guidelines for ethical conduct in the care and use of animals.

PMID- 16812446
TI  - The relationships between subject and experimenter (Editorial).

PMID- 16812448
TI  - Rule-governed behavior and sensitivity to changing consequences of responding.
AB  - Humans were presented with a task that required moving a light through a matrix.
      Button presses could produce light movements according to a multiple fixed-ratio
      18/differential-reinforcement-of-low-rate 6-s schedule, with components
      alternating every 2 min. Moving the light through the maze earned points worth
      chances on money prizes. In Experiment 1 four conditions were assessed through
      between-subject comparisons: minimal instructions, instructions to press rapidly,
      instructions to press slowly, and instructions that sometimes rapid responding
      would work while at other times a slow rate would work best. Subjects responded
      in three successive sessions of 32 min each. The results suggested that
      instructions affected the nature of the contact made with the programmed
      consequences and thus subsequent performance. In some cases, responding seemed to
      result from added contingencies introduced by stating rules. In Experiment 2 the
      relative contribution of these two effects was assessed by presenting and then
      withdrawing two lights that had been paired with two specific instructions: "Go
      Fast" or "Go Slow." There were three conditions. In one condition, only the Go
      Fast light was on; in a second, only the Go Slow light was on; and in a third,
      the lights alternated each minute. In each condition, half the subjects had all
      instruction lights turned off after the first session. The results once again
      showed an effect of instructions on contact with the programmed consequences.
      However, responding sometimes continued in a manner consistent with added
      contingencies for rule-following even when the programmed consequences had been
      contacted and would have controlled a different type of responding in the absence
      of instructions. The relevance of added contingencies for rule-following in
      determining the effects of explicitly programmed consequences is emphasized.

PMID- 16812449
TI  - Human concurrent performances: The effects of experience, instructions, and
      schedule-correlated stimuli.
AB  - In order to investigate the effects of separate exposures to single schedules, of
      unique schedule-correlated stimuli, and of independency-informing instructions
      upon choice under concurrent variable-interval schedules, 28 human subjects were
      divided into eight groups. Each subject was exposed to a baseline procedure, an
      experimental procedure, and a return to the baseline procedure. Different
      combinations of these three manipulations were applied to the different groups
      only during the experimental phase (except for the independency-informing
      instructions, which were given to half of the groups at the start of training).
      For the group of subjects exposed to the combination of all three manipulations,
      the logarithms of the ratios of response frequencies tended to be linearly
      related to the logarithms of the ratios of reinforcement frequencies during the
      experimental phase. These orderly effects were not obtained with subjects in the
      other groups. The results suggest that human choice was well described by the
      generalized matching law when the three manipulations were simultaneously in
      effect, and that unreported differences in the use of these three procedural
      variables might partly account for contradictions between results in previous
      studies of human concurrent performance.

PMID- 16812450
TI  - Allocation of complex, sequential operants on multiple and concurrent schedules
      of reinforcement.
AB  - Pigeons could produce food by pecking exactly four times on each of two keys, in
      any order. In the first experiment, these response sequences were reinforced on a
      series of multiple schedules of variable-interval reinforcement. In the second
      experiment, these response sequences were reinforced on a series of concurrent
      schedules of reinforcement. In both experiments, highly stereotyped response
      sequences developed. If these response sequences were treated as individual
      responses, the resulting data conformed to what is typically reported in studies
      of multiple and concurrent schedules involving individual responses. For example,
      behavioral contrast was observed with the multiple schedules, and matching was
      observed with the concurrent schedules. However, schedule manipulation had no
      effect on within-sequence characteristics of responses like accuracy, stereotypy,
      or rate. These data constitute further evidence that response sequences can
      become functional behavioral units.

PMID- 16812451
TI  - Varying response-reinforcer contiguity in a recycling conjunctive schedule.
AB  - Three experiments describe the effects of manipulating the frequency of response
      reinforcer contiguity in a recycling conjunctive schedule. The schedule arranged
      that a reinforcer was delivered after 30 s provided at least one response had
      occurred; otherwise the next cycle started immediately. In Experiment 1, this
      schedule produced the typical pause-respond-pause pattern, with most responses at
      mid-interval; and, when a limited number of contiguities between responses and
      food delivery were added, the pattern became more like the monotonic scallop seen
      on fixed-interval schedules. In Experiment 2, the schedule was initially
      presented with an additional contingency that allowed contiguity on every trial.
      Fixed-interval-like behavior occurred and tended to persist as contiguities were
      gradually eliminated. In Experiment 3, the recycling conjunctive schedule
      alternated with a condition in which a large number of contiguities occurred. The
      pause-respond-pause pattern and fixed-interval-like performance occurred with few
      or many contiguities, respectively. The results of all three experiments
      illustrate how contiguity interacts with a small number of other variables to
      determine performance on interval schedules and illuminate previous findings with
      fixed-interval and fixed-time schedules.

PMID- 16812452
TI  - Choice with a fixed requirement for food, and the generality of the matching
      relation.
AB  - Pigeons were trained on choice procedures in which responses on each of two keys
      were reinforced probabilistically, but only after a schedule requirement had been
      met. Under one arrangement, a fixed-interval choice procedure was used in which
      responses were not reinforced until the interval was over; then a response on one
      key would be reinforced, with the effective key changing irregularly from
      interval to interval. Under a second, fixed-ratio choice procedure, responses on
      either key counted towards completion of the ratio and then, once the ratio had
      been completed, a response on the probabilistically selected key would produce
      food. In one experiment, the schedule requirements were varied for both fixed
      interval and fixed-ratio schedules. In the second experiment, relative
      reinforcement rate was varied. And in a third experiment, the duration of an
      intertrial interval separating choices was varied. The results for 11 pigeons
      across all three experiments indicate that there were often large deviations
      between relative response rates and relative reinforcement rates. Overall
      performance measures were characterized by a great deal of variability across
      conditions. More detailed measures of choice across the schedule requirement were
      also quite variable across conditions. In spite of this variability, performance
      was consistent across conditions in its efficiency of producing food. The absence
      of matching of behavior allocation to reinforcement rate indicates an important
      difference between the present procedures and other choice procedures; that
      difference raises questions about the specific conditions that lead to matching
      as an outcome.

PMID- 16812453
TI  - Comparing the effects of two correction procedures on human acquisition of
      sequential behavior patterns.
AB  - Thirty-one college undergraduates learned to touch abstract stimuli on a computer
      screen in arbitrarily designated "correct" sequential orders. Four sets of seven
      stimuli were used; the stimuli were arrayed horizontally on the screen in random
      sequences. A correct response (i.e., touching first the stimulus designated as
      first) resulted in that stimulus appearing near the top of the screen in its
      correct sequential position (left to right), and remaining there until the end of
      the trial. Incorrect responses (i.e., touching a stimulus out of sequence)
      terminated the trial. New trials displayed either the same sequence as the one on
      which an error had occurred (same-order correction procedure), or a new random
      sequence (new-order correction procedure). Whenever all responses occurred in the
      correct sequence, the next trial displayed a new random sequence. Each phase
      ended when five consecutive correct response sequences occurred. Initially, the
      same-order correction procedure increased control by the position as well as by
      the shape of the stimuli; also, it produced more errors, more total trials, more
      trials to mastery, and more individual patterns of reacquisition than were
      produced by the new-order procedure.

PMID- 16812454
TI  - College students' responding to and rating of contingency relations: The role of
      temporal contiguity.
AB  - Two experiments investigated the role of temporal contiguity in college students'
      responding to and rating of contingency relations during operant conditioning.
      Schedules were devised that determined when but not whether appetitive or
      aversive events would occur. Subjects' reports concerning the schedules were
      obtained by means of a 200-point rating scale, anchored by the phrases "prevents
      the light from occurring" (-100) and "causes the light to occur" (+100). When
      tapping a telegraph key advanced the time of point gain, responding was
      maintained or increased and subjects gave positive ratings. When tapping a
      telegraph key advanced the time of point loss, subjects also gave positive
      ratings, but responding now decreased. When key tapping delayed the time of point
      gain, responding decreased and subjects gave negative ratings. When key tapping
      delayed the time of point loss, subjects also gave negative ratings, but
      responding now increased. These findings implicate response-outcome contiguity as
      an important contributor to causal perception and to reinforcement and punishment
      effects. Other accounts-such as those stressing the local probabilistic relation
      between response and outcome or the molar correlation between response rate and
      outcome rate-were seen to be less preferred interpretations of these and other
      results.

PMID- 16812455
TI  - Resistance to change produced by access to fixed-delay versus variable-delay
      terminal links.
AB  - Pigeons' responding was reinforced on a multiple schedule consisting of two two
      link chain schedules presented in regular alternation. Responding in initial
      links (always variable-interval 60-s) produced a key-color change and access to a
      terminal link. The terminal link for one chain provided food after a fixed delay
      (fixed-interval or fixed-time); the terminal link for the other provided food
      after a variable delay (variable-interval or variable-time). The average duration
      of the terminal-link schedules was varied across conditions, but in every
      condition the arithmetic mean of the variable-delay terminal-link schedule was
      equal to the duration of the fixed delay. Response rates were higher in the
      initial links of the chains with the variable-delay terminal links. Response
      decreasing operations (satiation, extinction) were used after performances
      reached asymptote. Response rates maintained by access to variable-delay terminal
      links tended to be more resistant to change than were rates maintained by access
      to fixed-delay terminal links. These results are consistent with the preference
      for variable- over fixed-interval terminal links observed with concurrent-chains
      schedules, suggesting (1) that immediacy of reinforcement influences the
      conditioned reinforcing potency of access to a terminal link and (2) that choice
      in concurrent chains and resistance of responding to change may be manifestations
      of the same effect of reinforcement.

PMID- 16812456
TI  - Instructions, multiple schedules, and extinction: Distinguishing rule-governed
      from schedule-controlled behavior.
AB  - Schedule sensitivity has usually been examined either through a multiple schedule
      or through changes in schedules after steady-state responding has been
      established. This study compared the effects of these two procedures when various
      instructions were given. Fifty-five college students responded in two 32-min
      sessions under a multiple fixed-ratio 18/differential-reinforcement-of-low-rate 6
      s schedule, followed by one session of extinction. Some subjects received no
      instructions regarding the appropriate rates of responding, whereas others
      received instructions to respond slowly, rapidly, or both. Relative to the
      schedule in operation, the instructions were minimal, partially inaccurate, or
      accurate. When there was little schedule sensitivity in the multiple schedule,
      there was little in extinction. When apparently schedule-sensitive responding
      occurred in the multiple schedule, however, sensitivity in extinction occurred
      only if differential responding in the multiple schedule could not be due to
      rules supplied by the experimenter. This evidence shows that rule-governed
      behavior that occurs in the form of schedule-sensitive behavior may not in fact
      become schedule-sensitive even though it makes contact with the scheduled
      reinforcers.

PMID- 16812457
TI  - Human operant performance: Sensitivity and pseudosensitivity to contingencies.
AB  - Undergraduates' button presses occasionally produced points exchangeable for
      money. Left and right buttons were initially correlated with multiple random
      ratio (RR) and random-interval (RI) components, respectively. During
      interruptions of the multiple schedule, students filled out sentence-completion
      guess sheets describing the schedules, and points were contingent upon the
      accuracy of guesses. To test for sensitivity to schedule contingencies, schedule
      components were repeatedly reversed between the two buttons. Pressing rates were
      consistently higher in ratio than in interval components even when feedback for
      guesses was discontinued, demonstrating sensitivity to the difference between
      ratio and interval contingencies. The question was whether this sensitivity was
      based directly on the contingencies or whether it was rule-governed. For two
      students, when multiple RR RI schedules were changed to multiple RI RI schedules,
      rates became low in both components of the multiple RI RI schedule; however,
      subsequent prevention of point deliveries for the first few responses in any
      component produced high rates in that component. For a third student, response
      rates became higher in the RI component that provided the lower rate of
      reinforcement. In each case, performance was inconsistent with typical effects of
      the respective schedules with nonhuman organisms; it was therefore plausible to
      conclude that the apparently contingency-governed performances were instead rule
      governed.

PMID- 16812458
TI  - Preference for less segmented fixed-time components in concurrent-chain schedules
      of reinforcement.
AB  - A concurrent-chain procedure was used to examine choice between segmented and
      less segmented response-independent schedules of reinforcement. A pair of
      independent, concurrent variable-interval 60-s schedules were presented in the
      initial link, along with a 1.5-s changeover delay. A chained fixed-interval fixed
      time and its corresponding tandem schedule constituted the terminal links. The
      length of the fixed-interval schedule in the terminal link was varied between 5 s
      and 30 s while that of the fixed-time schedule was kept at 5 s over conditions.
      The first components of both terminal-link schedules were accompanied by the same
      stimulus. Except in the baseline condition, the onset of the second component of
      the terminal-link chained schedule was accompanied by either a localized (key
      color) or a nonlocalized (dark houselight) stimulus change. Stimulus conditions
      were constant during the terminal-link tandem schedule. With three exceptions,
      pigeons demonstrated a slight preference for the tandem over the chained schedule
      in the terminal link. Furthermore, this preference varied inversely with the
      length of the first component. In general, these results are consistent with
      previous studies that reported an adverse effect on choice by segmenting an
      interval schedule into two or more components, but they are inconsistent with
      studies that reported preference for signaled over unsignaled delay of
      reinforcement.

PMID- 16812459
TI  - Behavioral contrast in competitive and noncompetitive environments.
AB  - Three experiments examined the effects of opportunities for an alternative
      response (drinking) on positive behavioral contrast of rats' food-reinforced bar
      pressing. In both Experiments 1 and 2 the baseline multiple variable-interval
      schedules were rich (variable interval 10-s), and contrast was examined both with
      and without a water bottle present. In Experiment 1, the rats were not water
      deprived. When one component of the multiple schedule was changed to extinction,
      the rate of bar pressing increased in the constant component (positive behavioral
      contrast). The magnitude of contrast was larger when the bottle was absent than
      when it was present, as predicted by the matching law. Drinking did not shift
      from the constant variable-interval component to the extinction component, as
      might have been expected from competition theory. In Experiment 2, the rats were
      water deprived. Contrast was larger when the bottle was present than when it was
      absent, and drinking did shift to the extinction component, as predicted by
      competition theory. In Experiment 3, water-deprived rats responded on leaner
      multiple variable-interval schedules (60-s) in the presence of a water bottle.
      When one component was changed to extinction, contrast did not occur, and
      drinking did not shift to the extinction component. The present results suggest
      that there are at least two different sources of behavioral contrast:
      "competitive" contrast, observed when an alternative response occurs with high
      probability, and "noncompetitive" contrast, observed when an alternative response
      occurs with low probability. The results, in conjunction with earlier studies,
      also suggest that the form of the alternative response and the rate of food
      reinforcement provided by the multiple schedule combine to determine the amount
      of contrast.

PMID- 16812460
TI  - Deprivation and satiation: The interrelations between food and wheel running.
AB  - Two experiments were designed to assess whether depriving rats of food would
      increase the reinforcement effectiveness of wheel running (Experiment 1) and
      whether satiation for wheel running would decrease the reinforcement
      effectiveness of food (Experiment 2). In Experiment 1, a progressive-ratio
      schedule was used to measure the reinforcement effectiveness of wheel running
      when rats were deprived or not deprived of food. Completion of a fixed number of
      lever presses released a brake on a running wheel for 60 s, and the response
      requirement was systematically increased until the rat stopped pressing or until
      8 hr had elapsed. The ratio value reached (and the total number of lever presses)
      was an inverted-U function of food deprivation (percentage body weight). In
      Experiment 2, when wheel running preceded test sessions, fewer food-reinforced
      lever presses were maintained by the progressive-ratio schedule, and responding
      occurred at a lower rate on a variable-interval schedule. An interpretation of
      these results is that deprivation or satiation with respect to one event (such as
      food) alters the reinforcement effectiveness of a different event (such as access
      to wheel running).

PMID- 16812461
TI  - Units of analysis and kinetic structure of behavioral repertoires.
AB  - It is suggested that molar streams of behavior are constructed of various
      arrangements of three elementary constituents (elicited, evoked, and emitted
      response classes). An eight-cell taxonomy is elaborated as a framework for
      analyzing and synthesizing complex behavioral repertoires based on these
      functional units. It is proposed that the local force binding functional units
      into a smoothly articulated kinetic sequence arises from temporally arranged
      relative response probability relationships. Behavioral integration is thought to
      reflect the joint influence of the organism's hierarchy of relative response
      probabilities, fluctuating biological states, and the arrangement of
      environmental and behavioral events in time.

PMID- 16812462
TI  - Escape from serial stimuli leading to food.
AB  - If the functional relations governing the strength of a conditioned reinforcer
      correspond to those obtained with other Pavlovian procedures (e.g., Kaplan,
      1984), the termination of stimuli appearing early in the interval between
      successive food deliveries should be reinforcing. During initial training we
      presented four key colors, followed by food, in a recurrent sequence to each of 6
      pigeons. This established a baseline level of autoshaped pecking. In later
      sessions, we terminated each of these colors or only the first color for a brief
      period following each peck, replacing the original color with a standard
      substitute to avoid darkening the key. Pecking decreased in the presence of the
      last color in the sequence but increased in the presence of the first. In accord
      with contemporary models of Pavlovian conditioning, these and other data suggest
      that the behavioral effects of stimuli in a chain may be better understood in
      terms of what each stimulus predicts, as measured by relative time to the
      terminal reinforcer, than in the exclusively positive terms of the traditional
      formulation (Skinner, 1938). The same model may also account for the initial
      pause under fixed-interval and fixed-ratio schedules of reinforcement.

PMID- 16812463
TI  - The effect of negative stimulus presentations on observing-response rates.
AB  - Theories of observing differ in predicting whether or not a signal for absence of
      reinforcement (S-) is capable of reinforcing observing responses. Experiments in
      which S- was first removed from and then restored to the procedure have yielded
      mixed results. The present experiments suggest that failure to control for the
      direct effect of presenting S- may have been responsible. Pigeons and operant
      procedures were used. Experiment 1 showed that presentations of S-, even when not
      contingent on observing, can raise the rate of an observing response that was
      reinforced only by presentations of a signal (S+) that accompanied a schedule of
      food delivery. Experiment 2 showed that this effect resulted from bursts of
      responding that followed offsets of S-. Experiment 3 showed that, when the
      presence of S- was held constant, lower rates occurred when S- was dependent on,
      rather than independent of, observing. These results support theories that
      characterize S- as incapable of reinforcing observing responses.

PMID- 16812464
TI  - Delayed reinforcement and delayed choice in symbolic matching to sample: Effects
      on stimulus discriminability.
AB  - Six pigeons were trained to peck a red side key when the brighter of two white
      lights (S(1)) had been presented on the center key, and to peck a green side key
      when the dimmer of two white lights (S(2)) had been presented on the center key.
      Equal frequencies of reinforcers were provided for the two types of correct
      choice. Incorrect choices, red side-key pecks following S(2) presentations and
      green side-key pecks following S(1) presentations, resulted in blackout. With 0-s
      delay between choice and reinforcement, the delay between sample presentation and
      choice was varied from 0 to 20 s. Then, with 0-s delay between sample
      presentation and choice, the delay between choice and reinforcement was varied
      from 0 to 20 s. Both types of delay resulted in decreased discriminability
      (defined in terms of a signal-detection analysis) of the center-key stimuli, but
      delayed choice had more effect on discriminability than did delayed
      reinforcement. These data are consistent with the view that the two kinds of
      delay operate differently. The effect of a sample-choice delay may result from a
      degradation of the conditional discriminative stimuli during the delay; the
      effect of a choice-reinforcer delay may result from a decrement in control by
      differential reinforcement.

PMID- 16812465
TI  - An assessment of the role of handling cues in "spontaneous recovery" after
      extinction.
AB  - Three experiments examined the assertion that presession handling cues that
      accompany training with reinforcement might account for spontaneous recovery when
      they reoccur following extinction. In Experiment 1, after extensive training on a
      variable-interval schedule, key pecking in pigeons was extinguished following
      either normal or distinctively different handling and transportational cues.
      Those cues resulted in enhanced spontaneous recovery 24 hr later when normal cues
      were reinstated. In Experiment 2, however, subjects tested following the normal
      handling cues showed no more spontaneous recovery than did subjects that spent
      the entire extinction-test interval in the experimental chambers and thus were
      tested without handling cues altogether. In Experiment 3, a group whose test for
      recovery began 10 min after being placed in the chambers yielded as much
      spontaneous recovery as did a group tested normally. Furthermore, a group for
      which extinction began at mid-session and for which handling therefore could not
      be a discriminative cue for extinction showed no more spontaneous recovery than
      did the other two groups. Handling cues thus contributed to spontaneous recovery
      only after explicit discrimination training, as provided in Experiment 1.

PMID- 16812466
TI  - On the measurement of time allocation on multiple variable-interval schedules.
AB  - Six pigeons were trained on a modified multiple-schedule procedure. In a three
      key chamber, the center key was lighted red or green, depending upon which
      component schedule was in effect. A response on this key transferred this color
      to each of two side keys, and responses on one of those keys produced reinforcers
      according to the component schedule. After 2 s, the side-key lights were
      extinguished, the center key was reilluminated, and a further center-key response
      was required to give access, as before, to the component schedules. Components
      alternated every 3 min. This limited-access procedure allowed both times spent
      switched into the side keys and time spent not switched in to be measured in the
      two components. Component reinforcer rates were varied over eight experimental
      conditions. Both component response rate and component time allocation were
      increasing functions of relative component reinforcer rate, and these functions
      were not significantly different. This finding implies that local response rates
      (responses divided by time switched in) were unaffected by changing component
      reinforcer rates on multiple schedules. Because a similar result was recently
      obtained for concurrent schedules, models of multiple and concurrent-schedule
      performance may need to consider only the time allocation of behavior emitted at
      equal tempo in the component schedules.

PMID- 16812467
TI  - Relative allocation on concurrent schedules can depend on schedule parameters
      when behavioral parameters are constant.
AB  - We develop a simple model of switching between the initial links of a concurrent
      chain procedure. Behavior is determined by four parameters mu(1), mu(2), q(1),
      and q(2). The first two are the basic rates of switching from Schedule 1 and
      Schedule 2, respectively. The second two are the probabilities of leaving
      Schedule 1 and Schedule 2 after the corresponding terminal link has been
      completed. We show that for fixed values of these four parameters, the relative
      allocation on the initial links may change as a result of changes in initial-link
      schedules. The effect can be quite large if the switching rates are low. An
      implication is that relative allocation is not necessarily a good measure of
      behavior.

PMID- 16812468
TI  - Consumption-leisure tradeoffs in pigeons: Effects of changing marginal wage rates
      by varying amount of reinforcement.
AB  - Pigeons' rates of responding and food reinforcement under simple random-ratio
      schedules were compared with those obtained under comparable ratio schedules in
      which free food deliveries were added, but the duration of each food delivery was
      halved. These ratio-with-free-food schedules were constructed so that, were the
      pigeon to maintain the same rate of responding as it had under the simple ratio
      schedule, total food obtained (earned plus free) would remain unchanged. However,
      any reduction in responding would reduce total food consumption below that under
      the simple ratio schedule. These "compensated wage decreases" led to decreases in
      responding and decreases in food consumption, as predicted by an economic model
      of labor supply. Moreover, the reductions in responding increased as the ratio
      value increased (i.e., as wage rates decreased). Pigeons, therefore, substituted
      leisure for consumption. The relationship between these procedures and negative
      income-tax programs is noted.

PMID- 16812469
TI  - Effects of response-allocation constraints on multiple-schedule performance.
AB  - Four pigeons were trained on multiple variable-interval schedules in which
      components alternated after a fixed number of responses had been emitted. In Part
      1, each component change occurred after 20 responses; in Part 2, the number was
      40; and in Part 3, the number of responses before change was 10. Component
      reinforcer rates were varied over five experimental conditions in each of Parts 1
      to 3. Component response rates decreased as the specified number of responses per
      component was increased. However, the relation between component response-rate
      ratios and component reinforcer-rate ratios was independent of the specified
      number of responses per component, and was similar to that found when components
      alternate after fixed time periods. In the fourth part of the experiment, the
      results from Parts 1 to 3 were systematically replicated by keeping the component
      reinforcer rates constant, but different, while the number of responses that
      produced component alternation was varied from 5 to 60 responses. The results
      showed that multiple-schedule performance under component-response-number
      constraint is similar to that under conventional component-duration constraint.
      They further suggest that multiple-schedule response rates are controlled by
      component reinforcer rates and not by principles of maximizing overall reinforcer
      rates or meliorating component reinforcer rates.

PMID- 16812470
TI  - Choosing among natural stimuli.
AB  - Pigeons worked on concurrent variable-interval, variable-interval schedules with
      the alternatives signaled by slides either containing trees or not. The schedules
      were designed to hold both overall and relative rates of reinforcement within
      narrowly constrained limits, and slides were quasi-randomly ordered each day.
      Responding to the two alternatives was well described by the generalized matching
      equation with substantial undermatching. Using an adaptation of the matching law,
      we estimated that the subjects were correctly classifying 82% to 95% of
      exemplars. The matching performance transferred to new exemplars of trees and
      nontrees with only slight generalization decrement. The pigeons appeared to be
      discriminating among exemplars even when the alternatives provided equal rates of
      reinforcement and the average relative performances were close to 50%.

PMID- 16812471
TI  - Sequential effects of interval duration on fixed-interval performance.
AB  - The bar pressing of rats was reinforced on a multiple fixed-interval schedule.
      The schedule intervals were 1 and 5 min long, and the sequence was such that
      intervals of either duration were equally likely to be followed by intervals of
      the same or of the other duration. Rates were higher during 1-min and after 5-min
      intervals. Best fit equations for cumulative responses during the 5-min intervals
      produced very similar exponents regardless of preceding duration. It was
      concluded that preceding duration may have affected the subjects' performances
      through direct effects on temporal discrimination.

PMID- 16812472
TI  - Intermittent reinforcement of a continuous response.
AB  - Six rats were trained with food deliveries contingent upon their pressing a lever
      and holding it down for either fixed or variable cumulative durations. Fixed-hold
      requirements ranged from 15 s to 90 s over experimental conditions; variable-hold
      requirements ranged from 15 s to 120 s. At most long and intermediate values,
      variable-hold requirements maintained more lever holding than fixed requirements.
      At the longest hold requirements studied, more lever holding was maintained by
      variable requirements than by fixed requirements of equivalent mean length for
      each rat. Postreinforcement-pause duration increased with lever-holding time for
      both fixed- and variable-hold requirements. At comparable lever-holding times per
      reinforcer, longer pauses typically were produced by fixed requirements than by
      variable requirements. Data from this study on the maintenance of responding,
      temporal response patterns, and postreinforcement pausing are comparable to those
      obtained with intermittent reinforcement of discrete responses. These findings
      suggest that the response-reinforcer relation specified by a reinforcement
      schedule is a fundamental determinant of responding, whether responding consists
      of discrete units or of continuous activity.

PMID- 16812474
TI  - Competitive fixed-interval performance in humans.
AB  - Two persons responded in the same session in separate cubicles, but under a
      single schedule of reinforcement. Each time reinforcement was programmed, only
      the first response to occur, that is, the response of only one of the subjects,
      was reinforced. "Competitive" behavior that developed under these conditions was
      examined in three experiments. In Experiment 1 subjects responded under fixed
      interval (FI) 30-s, 60-s, and 90-s schedules of reinforcement. Under the
      competition condition, relative to baseline conditions, the response rates were
      higher and the pattern was "break-and-run." In Experiment 2, subjects were
      exposed first to a conventional FI schedule and then to an FI competition
      schedule. Next, they were trained to respond under either a differential
      reinforcement-of-low-rate (DRL) or fixed-ratio (FR) schedule, and finally, the
      initial FI competition condition was reinstated. In this second exposure to the
      FI competition procedure, DRL subjects responded at lower rates than were emitted
      during the initial exposure to that condition and FR subjects responded at higher
      rates. For all subjects, however, responding gradually returned to the break-and
      run pattern that had occurred during the first FI competition condition.
      Experiment 3 assessed potential variables contributing to the effects of the
      competitive FI contingencies during Experiments 1 and 2. Subjects were exposed to
      FI schedules where (a) probability of reinforcement at completion of each fixed
      interval was varied, or (b) a limited hold was in effect for reinforcement. Only
      under the limited hold was responding similar to that observed in previous
      experiments.

PMID- 16812473
TI  - Variable-interval schedules of timeout from avoidance.
AB  - Rats were trained on concurrent schedules in which pressing one lever postponed
      shock and pressing the other occasionally produced a 2-min timeout during which
      the shock-postponement schedule was suspended and its correlated stimuli were
      removed. Throughout, the shock-postponement schedule maintained proficient levels
      of avoidance. Nevertheless, in Experiment 1 responding on the timeout lever was
      established rapidly, was maintained at stable levels on variable-interval
      schedules, was extinguished by withholding timeout, was reestablished when
      timeout was reintroduced, and was brought under discriminative control with a
      multiple variable-interval extinction schedule of timeout. These results are in
      contrast with Verhave's (1962) conclusion that timeout is an ineffective
      reinforcer when presented to rats on intermittent schedules. In Experiment 2 the
      consequence of responding on the timeout lever was altered so that the shock
      postponement schedule remained in effect even though the stimulus conditions
      associated with timeout were produced for 2 min. Responding extinguished,
      indicating that suspension of the shock-postponement schedule, not stimulus
      change, was the source of reinforcement. By establishing the reinforcing efficacy
      of timeout with standard variable-interval schedules, these experiments
      illustrate a procedure for studying negative reinforcement in the same way as
      positive reinforcement.

PMID- 16812475
TI  - The role of verbal behavior in human learning: III. Instructional effects in
      children.
AB  - Lever pressing of children from three age groups (2(1/2) to 4, 5 to 6(1/2), and
      7(1/2) to 9 years) could produce reinforcers according to a fixed-interval 40-s
      schedule: (1) Some were instructed to respond at a high rate, others at a low
      rate, and (2) they were subsequently taught to provide their own spoken self
      instructions consonant with the earlier, experimenter-supplied instructions. All
      subjects who received high-rate instructions responded at a steady, high rate,
      which was maintained following self-instructional training. The effects of low
      rate instructions were directly related to the age of the children. The two older
      groups produced low-rate patterns, with the oldest children responding at very
      low rates; effects were least noticeable in the youngest age group. Following
      self-instructional training, all three groups showed adult-like low-rate behavior
      and the oldest children showed an improved ability to estimate the interval
      length. The results provide further evidence of the importance of language as a
      determinant of human behavior.

PMID- 16812476
TI  - Optimal temporal differentiation.
AB  - In order to illuminate a light signaling a correct response, adult humans had to
      space their button presses according to a range of time requirements. In some
      conditions, the spacing needed only to exceed a minimum duration; in others, it
      had to fall between lower and upper bounds. Mean interresponse times always
      exceeded the lower limit, and decreased the more stringent were the upper bounds.
      Variability of interresponse times increased with larger lower bounds, but was
      unaffected by the size of the upper bound. Feedback about the direction of errors
      in conditions involving both upper and lower bounds did not affect the means, but
      it did reduce variability. Predictions were derived from optimality theory, based
      on the assumption that the critical factor was minimization of the time between
      correct responses. Without upper bounds, the theory overestimated the mean
      interresponse times by about 10%; with upper bounds, the theoretical predictions
      corresponded closely to the actual data. The results did not appear to reflect a
      scalar timing process. Optimality theory, in contrast to Weber's law, correctly
      predicted the variety of curves relating sensitivity to duration requirements.

PMID- 16812477
TI  - Control of responding during stimuli that precede transitions in reinforcement
      frequency.
AB  - Pigeons' responses were reinforced on a variant of a mixed variable-interval
      extinction schedule of reinforcement in which the transition to the higher
      reinforcement rate was signaled by a trace stimulus projected on the response key
      prior to the onset of the component correlated with food delivery. In the first
      of two experiments, the duration of the trace stimulus preceding the component
      correlated with food delivery was varied from 1.5 to 50.0 s and in the second
      experiment, the reinforcement frequency in the same component was varied from 10
      to 60 reinforcers per hour. Pigeons pecked at the trace stimulus preceding the
      onset of the component correlated with food delivery even though responding was
      not reinforced in its presence and only one of the changes in reinforcement rate
      (i.e., from extinction to reinforcement) was signaled. The rate of pecking during
      the trace stimulus was a function of its duration but not of the reinforcement
      frequency in the following component. Higher rates generally occurred at the
      shorter trace-stimulus durations. Component responding following the offset of
      the trace stimulus was under discriminative control of the trace stimulus whether
      or not responding occurred in the presence of the trace stimulus.

PMID- 16812479
TI  - Editorial.

PMID- 16812478
TI  - Shaping by automated tracking of an arbitrary operant response.
AB  - Although shaping is a widely accepted operant-conditioning procedure for
      establishing new responses, technological problems involved in specifying and
      recording precise approximations to the target response have hindered
      experimental analysis of the shaping process. The present study used a computer
      controlled system that allows relatively precise procedural specification by
      continuous tracking of a pigeon's head and reinforcing successively closer
      approximations to contact of the head with an arbitrary fixed spherical region of
      3-cm diameter. The procedure was demonstrated to be effective, in that shaping of
      the target response occurred rapidly for each of the 3 birds in the study.

PMID- 16812480
TI  - Superstitious behavior in humans.
AB  - Twenty undergraduate students were exposed to single response-independent
      schedules of reinforcer presentation, fixed-time or variable-time, each with
      values of 30 and 60 s. The reinforcer was a point on a counter accompanied by a
      red lamp and a brief buzzer. Three color signals were presented, without
      consistent relation to reinforcer or to the subjects' behavior. Three large
      levers were available, but the subjects were not asked to perform any particular
      behavior. Three of the 20 subjects developed persistent superstitious behavior.
      One engaged in a pattern of lever-pulling responses that consisted of long pulls
      after a few short pulls; the second touched many things in the experimental
      booth; the third showed biased responding called sensory superstition. However,
      most subjects did not show consistent superstitious behavior. Reinforcers can
      operate effectively on human behavior even in the absence of a response
      reinforcer contingency and can, in some cases, shape stable superstitious
      patterns. However, superstitious behavior is not a consistent outcome of exposure
      of human subjects to response-independent reinforcer deliveries.

PMID- 16812481
TI  - The operant conditioning of response variability: Free-operant versus discrete
      response procedures.
AB  - The operant conditioning of response variability under free-operant and discrete
      response procedures was investigated. Two pigeons received food only if their
      pattern of four pecks on two response keys differed from the patterns emitted on
      the two immediately preceding trials. Under the free-operant procedure, the keys
      remained illuminated and operative throughout each trial. There was little
      variability in the response patterns that resulted, and the pigeons received
      fewer than one third of the available reinforcers. Under the discrete-response
      procedure, a brief timeout period followed each response. Variability increased
      under this procedure, and the pigeons obtained three fourths of the available
      reinforcers. Previous successes and failures to produce response variability may
      have been due to the use or failure to use, respectively, a discrete-response
      procedure. Respondent effects inherent in the free-operant procedure may
      encourage the development of response stereotypy and, in turn, prevent the
      development of response variability.

PMID- 16812482
TI  - Conditional relations by monkeys: Reflexivity, symmetry, and transitivity.
AB  - Two cynomolgous macaques categorized six colors into two groups of three after
      conditional discrimination training (zero-delay symbolic match-to-sample). The
      procedures resulted in the establishment of relations among the elements of each
      set-relations that were not specifically trained and that can be characterized by
      the properties of reflexivity, symmetry, and transitivity. Each set of colors was
      related to a characteristic pattern of responding: One response pattern involved
      temporal duration (press and hold the response keys); the second response pattern
      entailed repeated pressing and releasing of the response keys (fixed ratio 8).
      Six combinations of two colors were trained, three combinations from each set.
      After discriminative performance stabilized for each monkey, they were tested
      with 10 additional color combinations, all of which differed from the training
      combinations. The conditional relations established between test combinations can
      be characterized as stimulus equivalence. The training procedures were analogous
      to the procedure of using category names, and have implications for understanding
      the function of language in the formation of equivalence classes.

PMID- 16812483
TI  - Delayed temporal discrimination in pigeons: A comparison of two procedures.
AB  - A within-subjects comparison was made of pigeons' performance on two temporal
      discrimination procedures that were signaled by differently colored keylight
      samples. During stimulus trials, a peck on the key displaying a slanted line was
      reinforced following short keylight samples, and a peck on the key displaying a
      horizontal line was reinforced following long keylight samples, regardless of the
      location of the stimuli on those two choice keys. During position trials, a peck
      on the left key was reinforced following short keylight samples and a peck on the
      right key was reinforced following long keylight samples, regardless of which
      line stimulus appeared on the correct key. Thus, on stimulus trials, the correct
      choice key could not be discriminated prior to the presentation of the test
      stimuli, whereas on position trials, the correct choice key could be
      discriminated during the presentation of the sample stimulus. During Phase 1,
      with a 0-s delay between sample and choice stimuli, discrimination learning was
      faster on position trials than on stimulus trials for all 4 birds. During Phase
      2, 0-, 0.5-, and 1.0-s delays produced differential loss of stimulus control
      under the two tasks for 2 birds. Response patterns during the delay intervals
      provided some evidence for differential mediation of the two delayed
      discriminations. These between-task differences suggest that the same processes
      may not mediate performance in each.

PMID- 16812484
TI  - Topographical variations in behavior during autoshaping, automaintenance, and
      omission training.
AB  - Three pigeons were exposed to an autoshaping and automaintenance procedure while
      a computer-controlled tracking system continuously recorded the position of the
      bird's head as it moved freely in the experimental chamber. Although only 2 birds
      pecked the key during the conditional stimulus (red keylight), all 3 birds
      exhibited stable patterns of approaching the conditional stimulus and withdrawing
      from the intertrial stimulus (white keylight). Subsequent exposure to an omission
      procedure, in which pecks on the red key cancelled the presentation of food upon
      the termination of the red keylight, greatly reduced key pecking, but approaching
      and pecking in the vicinity of the conditional stimulus were maintained at high
      levels. When the omission contingency was removed key pecking increased. During
      all phases the birds withdrew from the area of the white key and engaged in
      repetitive back-and-forth or circuiting movements during this intertrial
      stimulus. The data document (a) the strong control the conditional stimulus in
      autoshaping and automaintenance exerts over approach to the key and pecking
      motions whether or not the conditional stimulus elicits key pecking at a high
      level; and (b) withdrawal from the vicinity of the key and the occurrence of
      stereotypic behavior during the intertrial interval.

PMID- 16812485
TI  - The maximization of overall reinforcement rate on concurrent chains.
AB  - We model behavioral allocation on concurrent chains in which the initial links
      are independent variable-interval schedules. We also quantify the relationship
      between behavior during the initial links and the probability of entering a
      terminal link. The behavior that maximizes overall reinforcement rate is then
      considered and compared with published experimental data. Although all the trends
      in the data are predicted by rate maximization, there are considerable deviations
      from the predictions of rate maximization when reward magnitudes are unequal. We
      argue from our results that optimal allocation on concurrent chains, and prey
      choice as used in the theory of optimal diets, are distinct concepts. We show
      that the maximization of overall rate can lead to apparent violations of
      stochastic transitivity.

PMID- 16812486
TI  - Remote effects of aversive contingencies: Disruption of appetitive behavior by
      adjacent avoidance sessions.
AB  - Disruption of ongoing appetitive behavior before and after daily avoidance
      sessions was examined. After baselines of appetitive responding were established
      under a fixed-interval 180-s schedule of food presentation, 4 rats were exposed
      to 40-min sessions of the appetitive schedule just prior to 100-min sessions of
      electric shock postponement, while another 4 rats received the 40-min appetitive
      sessions just following daily sessions of shock postponement. In all 8 subjects,
      fixed-interval response rates decreased relative to baseline levels, the effect
      being somewhat more pronounced when the avoidance sessions immediately followed.
      The disruption of fixed-interval responding was only partially reversed when
      avoidance sessions were discontinued. During the initial exposure to the
      avoidance sessions, patterns of responding under the fixed-interval schedule were
      differentially sensitive to disruption, with high baseline response rates
      generally more disturbed than low rates. These disruptions were not
      systematically related to changes in reinforcement frequency, which remained
      fairly high and invariant across all conditions of the experiment; they were also
      not systematically related to the response rates or to the shock rates of the
      adjacent avoidance sessions. The results, while qualitatively resembling patterns
      of conditioned suppression as typically studied, occurred on a greatly expanded
      time scale. As disruption of behavior extending over time, the present data
      suggest that some forms of conditioned suppression are perhaps best viewed within
      a larger temporal context.

PMID- 16812487
TI  - Does contingent reinforcement strengthen operant behavior?
AB  - In Experiment 1, pigeons were trained to peck keys with equal food-reinforcement
      schedules in components that ended with either noncontingent or contingent
      transitions to a third component with a five-fold richer schedule. Response rates
      were higher in the initial component with contingent transitions, but resistance
      to prefeeding or extinction was not consistently greater. Experiment 2 also
      included noncontingent or contingent transitions to a signaled period of
      nonreinforcement. There was no effect of the contingency on transitions to
      nonreinforcement, but the difference in response rates maintained by contingent
      versus noncontingent transitions to the richer schedule was replicated. In
      addition, response rates were higher in components that preceded nonreinforcement
      than in components that preceded the richer schedule. However, resistance to
      extinction was greater for noncontingent transitions to the richer schedule than
      to nonreinforcement, implicating stimulus-reinforcer relations in the
      determination of resistance to change. Resistance to change was also somewhat
      greater for noncontingent than for contingent transitions to the richer schedule.
      The latter result, together with the results of Experiment 1 and related
      research, suggests that response-contingent reinforcement does not increase
      resistance to change.

PMID- 16812488
TI  - Stimulus- and pellet-induced drinking during a successive discrimination.
AB  - In three experiments, interim water drinking was examined in rats exposed to a
      multiple schedule whose two components were extinction and a variable-time 30-s
      schedule of food delivery. Two different drinking patterns were observed in
      Experiment 1. Pellet-induced drinking, characterized by high rates of postpellet
      drinking in the variable-time component, with little or no drinking in
      extinction, occurred when the acquisition of stable postpellet drinking preceded
      discrimination training. Stimulus-induced drinking, characterized by a burst of
      drinking at the onset of extinction, with no drinking during the variable-time
      schedule, occurred when discrimination training preceded all other experimental
      conditions. With extended training, stimulus-induced drinking eventually was
      accompanied by postpellet drinking. In Experiment 2, the rate of stimulus-induced
      drinking and the number of sessions during which it occurred without postpellet
      drinking were found to be inversely related to component duration. In Experiment
      3, the rate of schedule-induced drinking was found to vary directly with
      component duration.

PMID- 16812489
TI  - Feedback effects on sequential ordering in humans.
AB  - Under various feedback conditions, 38 college undergraduates were asked to
      rearrange abstract graphic characters on a computer screen, placing them in
      arbitrarily designated "correct" sequences. Two sets of seven horizontally
      arrayed stimuli were used. In Experiment 1, subjects in Group 1 learned to
      arrange the first set under Selection Feedback in which a "+" appeared above each
      character after it was selected in the correct order and to arrange the second
      set under Order Feedback in which a correct response produced a copy of the
      character in its correct ordinal position at the top of the screen. For Group 2
      the order of these conditions was reversed. In Experiment 2, for subjects in
      Group 3, correct responses produced neither of these types of feedback. Subjects
      in Group 4 received Order Feedback only until the first set was correctly ordered
      once. Order Feedback was more effective than Selection Feedback during initial
      acquisition of the first set but not during maintenance; no differences were
      found for the second set. Only 2 of 9 subjects successfully put the characters in
      correct sequential order under the No Feedback condition. When, in Experiment 2,
      Order Feedback was eliminated after the first correctly arranged sequence, the
      steady-state criteria were met more slowly than in Experiment 1.

PMID- 16812490
TI  - Interpersonal contingencies: Performance differences and cost-effectiveness.
AB  - Three reinforcement contingencies were compared with regard to performance
      differences and cost-effectiveness (i.e., responses per unit reinforcer). Pairs
      of college students were studied under individual, cooperative, or competitive
      contingencies using a concurrent setting that included one of these three
      contingencies as one alternative and a lower paying individual contingency as the
      other alternative. With the individual and the cooperative contingencies, overall
      response rates were typically high; under competitive contingencies the overall
      response rates were substantially lower. Subjects responded at very high rates
      when competing, but chose not to compete most of the time. Competition and
      cooperation produced the most cost-effective responding, assessed as the number
      of responses made per $.01 of reinforcer. High overall rates of competitive
      responding were obtained when the contests were longer and the lower paying
      alternative contingency was not available.

PMID- 16812491
TI  - Sensitivity to reinforcer duration in a self-control procedure.
AB  - In a concurrent-chains procedure, pigeons' responses on left and right keys were
      followed by reinforcers of different durations at different delays following the
      choice responses. Three pairs of reinforcer delays were arranged in each session,
      and reinforcer durations were varied over conditions. In Experiment 1 reinforcer
      delays were unequal, and in Experiment 2 reinforcer delays were equal. In
      Experiment 1 preference reversal was demonstrated in that an immediate short
      reinforcer was chosen more frequently than a longer reinforcer delayed 6 s from
      the choice, whereas the longer reinforcer was chosen more frequently when delays
      to both reinforcers were lengthened. In both experiments, choice responding was
      more sensitive to variations in reinforcer duration at overall longer reinforcer
      delays than at overall shorter reinforcer delays, independently of whether fixed
      interval or variable-interval schedules were arranged in the choice phase. We
      concluded that preference reversal results from a change in sensitivity of choice
      responding to ratios of reinforcer duration as the delays to both reinforcers are
      lengthened.

PMID- 16812492
TI  - Income and choice between different goods.
AB  - In Experiment 1, 3 rats chose between two simultaneously operating variable
      interval schedules, one of which provided saccharin water and the other, food. In
      five conditions, the absolute (and equal) reinforcement rates provided by the
      pair of equal-valued schedules were manipulated in the range of 36 to 240 per
      hour. Experiment 2 was identical to Experiment 1 except that these schedules
      operated successively, arranged by requiring the rat to stand on the side of the
      chamber correlated with each schedule. Food/saccharin choice ratios were
      inversely related to reinforcement rate in both experiments, although this effect
      was stronger in Experiment 2. When delivery rates were high, preference for food
      over saccharin often reversed as the session progressed. The results were
      interpretable in terms of economic accounts of choice (e.g., the minimum-needs
      hypothesis), as well as in terms of traditional psychological accounts (e.g.,
      matching theory).

PMID- 16812493
TI  - Factors affecting conditional discrimination learning by pigeons.
AB  - In Experiment 1 (within subjects) and Experiment 2 (between subjects) it was
      shown that the sequential training of pigeons on a color discrimination and then
      on its reversal, each in a different floor-tilt/texture context, failed to
      produce conditional control of discriminative performance by those contexts.
      Daily alternation between the two problems (with correlated contexts) was
      successful, however. In each of these experiments conditional control was better
      reflected in generalization test performance in extinction than during sessions
      of training with reinforcement.

PMID- 16812494
TI  - The structure of equivalence classes.
AB  - THE STRUCTURE OF EQUIVALENCE CLASSES CAN BE COMPLETELY DESCRIBED BY FOUR
      PARAMETERS: class size, number of nodes, the distribution of "singles" among
      nodes, and directionality of training. Class size refers to the number of stimuli
      in a class. Nodes are stimuli linked by training to at least two other stimuli.
      Singles are stimuli linked by training to only one other stimulus. The
      distribution of singles refers to the number of singles linked by training to
      each node. Directionality of training refers to the use of stimuli as samples and
      as comparison stimuli in training. These four parameters define the different
      ways in which the stimuli in a class can be organized, and thus provide a basis
      for systematically characterizing the properties of stimuli in a given
      equivalence class. The four parameters can also be used to account for the
      development of individual differences that are commonly characterized in terms of
      "understanding" and connotative meaning.Methods are described for generating all
      possible combinations of parameter values, and a formula is introduced which
      specifies all of the parameter values for an equivalence class. Its utility for
      interrelating experimental procedures is demonstrated by analyzing a number of
      representative experiments that have addressed equivalence-class formation.

PMID- 16812495
TI  - Reply to silberberg and ziriax.
AB  - Silberberg and Ziriax (1985) report that a modification of Vaughan's (1981)
      procedure produces results inconsistent with melioration (the position advocated
      by Vaughan) but consistent with a process they term molecular maximizing. Here it
      is argued that the theory of molecular maximization is not sufficiently
      unambiguous that researchers other than the developers can test its predictions,
      and that in any case none of the data presented by Silberberg and Ziriax are both
      clearly consistent with molecular maximization and inconsistent with melioration.

PMID- 16812496
TI  - Commentary prompted by Vaughan's Reply to Silberberg and Ziriax by Alan
      Silberberg and John M. Ziriax, and by William Timberlake, with concluding remarks
      by William Vaughan, Jr.

PMID- 16812497
TI  - Probability and delay in commitment.
AB  - In the first stage of a two-stage choice, human subjects chose between
      probabilistic access to a second choice (between a small high-probability reward
      and a large low-probability reward) and commitment to the large low-probability
      reward. When confronted with the second-stage choice, subjects strongly preferred
      the small high-probability reward. When the first-stage probability (of access to
      the second stage) was high, subjects strongly preferred the path leading to the
      choice in the second stage. But when the first-stage probability was low,
      subjects committed themselves to the large low-probability reward. These results
      parallel those obtained by Rachlin and Green (1972) with pigeons and constitute
      some evidence that probabilities may be interpreted as delays.

PMID- 16812498
TI  - Dissociation of value and response strength.
AB  - Four pigeons were exposed to multiple schedules and later to concurrent-chains
      schedules, with terminal links that had previously been multiple-schedule
      components. For 2 birds, the terminal-link schedules arranged an inverse
      relationship between response rate and reinforcement rate; for the other 2 birds
      a direct corresponding relationship was arranged. Those response rates were
      further modified by differentially reinforcing either longer or shorter
      interresponse times, relative to the current means. Although the birds' initial
      link responses indicated preferences for terminal links with higher rates of
      reinforcement, in half the cases the birds responded during the terminal links in
      such a way as to produce lower rates of reinforcement, rates their initial-link
      behavior indicated they did not prefer. That outcome is inconsistent with
      maximization theory, but consistent with a strengthening analysis of behavior on
      single-key schedules.

PMID- 16812499
TI  - Response-reinforcer relations and the maintenance of behavior.
AB  - The effects on pigeons' key pecking of unsignaled delays of reinforcement and
      response-independent reinforcement were compared after either variable-interval
      or differential-reinforcement-of-low-rate baseline schedules. One 30-min session
      arranging delayed reinforcement and one 30-min session arranging response
      independent reinforcement were conducted daily, 6 hr apart. A within-subject
      yoked-control procedure equated reinforcer frequency and distribution across the
      two sessions. Response rates usually were reduced more by response-independent
      than by delayed but response-contingent delivery of reinforcers. Under both
      schedules, response rates were lower when obtained delays were greater. These
      results bear upon methodological and conceptual issues regarding comparisons of
      contingencies that change the temporal response-reinforcer relations.

PMID- 16812500
TI  - A comparison of response patterns on fixed-, variable-, and random-ratio
      schedules.
AB  - The behavior of individual pigeons on fixed-ratio, variable-ratio, and random
      ratio schedules was examined. Within each type of ratio schedule the size of the
      ratio was varied in an irregular sequence. At various ratio sizes (5, 10, 40, 80)
      no differences were found among overall response rates (postreinforcement pause
      plus running response rate) as a function of ratio type. This similarity in
      overall response rates held despite noticeable differences in the microstructure
      of performance both within and across subjects; the primary performance
      difference on the three types of ratio schedules was the relatively longer
      postreinforcement pause duration on the fixed-ratio schedule. We concluded that
      the gross temporal characteristics of performance determined by the relative
      weightings of the postreinforcement pause and running response rate were
      primarily controlled by the type of ratio schedule (fixed, variable, or random),
      whereas the overall rate of responding was controlled by the size of the ratio.

PMID- 16812501
TI  - A role for negative reinforcement of response omission in punishment?
AB  - This experiment attempted to disentangle response-rate reductions controlled by
      the direct suppressive effects of a punisher from those due to negative
      reinforcement of response omission. Key-peck responding of pigeons was maintained
      by a conjoint variable-interval 3-min schedule of food presentation variable
      interval 30-s schedule of response-dependent electric shock presentation.
      Omission of responses for 5, 10, or 30 s resulted in the possibility of canceling
      a scheduled shock. Response rates were a function of required pause duration,
      with lower rates occurring when longer periods of response omission were required
      for shock cancellation. These results show that, with several parameters of
      punishment held constant, response rates were controlled by the negative
      reinforcement contingency. Such a finding argues for renewed consideration of the
      role of negative reinforcement in punishment contingencies.

PMID- 16812502
TI  - Punishment of schedule-induced drinking in rats by signaled and unsignaled delays
      in food presentation.
AB  - Food-deprived rats were exposed to a fixed-time 60-s schedule of food-pellet
      presentation and developed schedule-induced drinking. Using an ABA reversal
      design, three experiments investigated the effects of events then made dependent
      on licks. In Experiment 1, lick-dependent signaled delays (10 s) in food
      presentation in general led to decreased drinking, which recovered when the
      signaled delays were discontinued. The drinking of yoked-control rats, which
      received food at the same times as those exposed to the signaled-delay
      contingency, showed much smaller changes. Experiment 2 showed that 10-s lick
      dependent signals alone did not reduce drinking. In Experiment 3, when licks
      produced unsignaled 10-s delays in food there were less marked and more gradual
      changes in drinking than in Experiment 1, although these effects again were
      greater than with yoked-control animals. We concluded that both signaled and
      unsignaled delays functioned as punishers of drinking. These findings support the
      view that schedule-induced drinking, like operant behavior, is subject to control
      by its consequences.

PMID- 16812503
TI  - An automatic pellet dispenser for precise control of feeding topography in
      granivorous birds.
AB  - Design and construction of an automatic pellet dispenser for granivorous birds
      are described. The dispenser permits rapid pneumatic delivery of pellets (five
      pellets per second maximum) to one controlled position and does not interfere
      with simultaneous electrophysiological recording. In addition, the device
      continuously indicates presence or absence of a pellet in the delivery position.
      This automatic dispenser proved very effective in our studies of stereotyped
      topographies of feeding in granivorous birds, such as pigeons and chickens.

PMID- 16812504
TI  - Introduction.

PMID- 16812505
TI  - A visit to Bloomington: The first Conference on the Experimental Analysis of
      Behavior.

PMID- 16812506
TI  - Antecedents.

PMID- 16812507
TI  - Reminiscences already?

PMID- 16812508
TI  - Columbia gems.

PMID- 16812509
TI  - The Yerkes connection.

PMID- 16812510
TI  - Back to baseline.

PMID- 16812511
TI  - An outsider on the inside.

PMID- 16812512
TI  - Faded images.

PMID- 16812513
TI  - Reminiscences, you say?

PMID- 16812514
TI  - Counterpoint.

PMID- 16812515
TI  - Collecting the first dollars for JEAB.

PMID- 16812516
TI  - "Money's the cheapest thing we've got"?

PMID- 16812517
TI  - Memories of JEAB's mother.

PMID- 16812518
TI  - How it was being second.

PMID- 16812519
TI  - Behavior in the beginning.

PMID- 16812520
TI  - Editorial selection.

PMID- 16812521
TI  - Uncertain days-.

PMID- 16812523
TI  - Two sides of behavior.

PMID- 16812522
TI  - Double duty.

PMID- 16812524
TI  - Variation and progress.

PMID- 16812525
TI  - Self-conscious behavior analysis.

PMID- 16812526
TI  - Society for the Experimental Analysis of Behavior: The first thirty years (1957
      1987).

PMID- 16812527
TI  - A special tribute to Ralph Gerbrands.

PMID- 16812528
TI  - Editorial.

PMID- 16812529
TI  - Successive independence of multiple-schedule component performances.
AB  - In three experiments, pigeons' responses were reinforced on two keys in each
      component of a series of multiple-schedule conditions. In each series, concurrent
      variable-interval schedules were constant in one component and were varied over
      conditions in the other component. In the first experiment both components
      arranged the same, constant total number of reinforcers, in the second the two
      components arranged constant but different totals, and in the third experiment
      the total was varied in one component and remained constant in the other.
      Relative reinforcer rate during the varied component was manipulated over
      conditions in all three experiments. In all these experiments, response and time
      allocation in the constant component were invariant when reinforcer ratios varied
      in the other component, demonstrating independence of behavior allocation in a
      multiple-schedule component from the relative reinforcer rate for the same
      alternatives in another component. In the two experiments which maintained
      constant reinforcer totals in components, sensitivity to reinforcement in the
      multiple schedules was the same as that in the concurrent schedules arranged
      during the varied component, with multiple-schedule bias in the experiment in
      which the totals were unequal.

PMID- 16812530
TI  - Concurrent-schedule performance: Effects of relative and overall reinforcer rate.
AB  - Six pigeons were trained to respond on two keys, each of which provided
      reinforcers on an arithmetic variable-interval schedule. These concurrent
      schedules ran nonindependently with a 2-s changeover delay. Six sets of
      conditions were conducted. Within each set of conditions the ratio of reinforcers
      available on the two alternatives was varied, but the arranged overall reinforcer
      rate remained constant. Each set of conditions used a different overall
      reinforcer rate, ranging from 0.22 reinforcers per minute to 10 reinforcers per
      minute. The generalized matching law fit the data from each set of conditions,
      but sensitivity to reinforcer frequency (a) decreased as the overall reinforcer
      rate decreased for both time allocation and response allocation based analyses of
      the data. Overall response rates did not vary with changes in relative reinforcer
      rate, but decreased with decreases in overall reinforcer rate. Changeover rates
      varied as a function of both relative and overall reinforcer rates. However, as
      explanations based on changeover rate seem unable to deal with the changes in
      generalized matching sensitivity, discrimination accounts of choice may offer a
      more promising interpretation.

PMID- 16812531
TI  - G. S. Reynolds (1936-1987).

PMID- 16812532
TI  - Reinforcement schedules: Retroactive and proactive effects of reinforcers
      inserted into fixed-interval performances.
AB  - The responding maintained by a reinforcer depends on the relation of the
      reinforcer not merely to the response that produces it but also to other
      preceding responses. Early responses in a sequence that ends in a reinforcing
      consequence make smaller contributions to later response rates than more recent
      ones, by virtue of the longer delays that separate them from the reinforcer. This
      study shows that the relation between a response and a later reinforcer
      contributes to responding only if no other reinforcers intervene; in other words,
      each reinforcer blocks responses that precede it from the effects of later
      reinforcers. Pigeons' pecks were maintained by fixed-interval (FI) schedules of
      food reinforcement. When FI 60-s (short) and FI 75-s (long) schedules began
      simultaneously within constant 150-s cycles, long FIs did not affect short-FI
      performances, but short FIs eliminated the first 60 s of long-FI performances.
      Removing either short-FI reinforcers or short-FI stimuli showed that short-FI
      reinforcers and not short-FI stimuli blocked the first 60 s of the long-FI
      performance from the retroactive effects of the long-FI reinforcer. With FI 15-s
      and FI 75-s schedules, the short-FI reinforcer was followed by reduced long-FI
      responding, but a schedule that prevented discrimination based on time since a
      reinforcer eliminated this proactive effect of the short-FI reinforcer. In other
      words, the retroactive effects were reinforcer effects whereas the proactive
      effects were discriminative effects. Quantitative descriptions of variable
      interval performances, in which reinforcer effects may operate in the absence of
      temporal discriminative effects, can be derived from these relations.

PMID- 16812533
TI  - Effects of magnitude of food reinforcement on free-operant response rates.
AB  - In Experiment 1 rats were trained to press a lever on a variable-ratio schedule
      of food presentation and were then exposed to progressively increasing magnitudes
      of food reinforcement. Response running rates (rates exclusive of the
      postreinforcement pause) were found to increase as a function of increasing
      reinforcement magnitudes. The effect of reinforcement magnitude on response rates
      inclusive of the postreinforcement pause, however, was less pronounced. Increases
      in the magnitude of reinforcement were also found to increase the length of the
      postreinforcement pause. Rats in Experiment 2 were trained to respond on a
      chained differential-reinforcement-of-low-rate variable-ratio schedule, and were
      exposed to increasing magnitudes of reinforcement as in Experiment 1. Response
      running rates increased in the variable-ratio component but decreased in the
      other component of the schedule. The results are discussed with reference to
      incentive accounts of reinforcement and the action of reinforcement on the
      response units generated by the operative contingencies.

PMID- 16812534
TI  - Some effects of response-correlated increases in reinforcer magnitude on human
      behavior.
AB  - After training under short or long fixed-interval schedules, humans responded
      under a modified fixed-interval schedule in which magnitude of reinforcement (X
      or 2X) was minimally correlated with response frequency. Response frequencies
      that equaled or exceeded a minimum response criterion were followed by the larger
      reinforcer at the end of the interval; otherwise, the smaller reinforcer was
      delivered. The modified schedule alternated with the baseline schedule across
      conditions. In a control condition, the reinforcer magnitudes produced by control
      subjects were yoked to those of experimental subjects. Experimental subjects, but
      not control subjects, showed increased responding. In addition to the baseline
      and modified fixed-interval schedules used in Experiment 1, subjects in
      Experiment 2 also responded under a second modified fixed-interval contingency in
      which increases in reinforcer magnitude were more highly correlated with response
      frequency. Experimental subjects, but not control subjects, showed increased
      responding under both procedures. Direct comparison of these two procedures
      showed that the high-correlation procedure produced greater increases in
      responding than did the low-correlation procedure.

PMID- 16812535
TI  - Preference for simple interval schedules of reinforcement in concurrent chains:
      Effects of segmentation ratio.
AB  - A concurrent-chains procedure was used to examine pigeons' preferences between
      segmented and unsegmented terminal-link schedules of reinforcement. During the
      initial link, a pair of independent, concurrent variable-interval 60-s schedules
      was in effect. In the terminal link, reinforcement was provided by a chain fixed
      interval fixed-interval schedule on one key and by a simple fixed-interval
      schedule with an equal interreinforcement interval in the other. The relative
      duration between the first and second components (segmentation ratio) in the
      terminal-link chained schedule was systematically varied while the terminal-link
      duration was kept constant at either 15 s or 30 s in two sets of conditions. With
      few exceptions, the simple schedule was preferred to the chained schedule.
      Furthermore, this preference was inversely related to the size of the
      segmentation ratio in the segmented schedule. When the segmentation ratio was
      smaller than 1:1, preference was more extreme for a 30-s condition than for a 15
      s condition. However, preference decreased more rapidly in conditions with the
      longer terminal-link duration when the ratio increased. Taken together, these
      results were consistent with previous findings concerning the effect of the
      terminal-link duration on choice between segmented and unsegmented schedules. In
      addition, the data suggested that segmentation ratio in a segmented schedule
      constitutes another potent factor influencing preference for the unsegmented
      schedule.

PMID- 16812536
TI  - Self-control in male and female rats.
AB  - Eight male and 8 female Wistar rats were exposed to a discrete-trial procedure in
      which they chose between the presentation of a small (one pellet) or a large
      (three pellets) reinforcer. The delay to the small and large reinforcer was 6.0 s
      in the first condition of Experiment 1. Subjects consistently chose the large
      reinforcer. When the delay to the small reinforcer was decreased to 0.1 s in the
      next experimental condition, all subjects continued to choose the large 6.0-s
      delayed reinforcer. When the contingencies correlated with the two levers were
      reversed in the next experimental condition, the majority of subjects (5 males
      and 6 females) still chose the large delayed reinforcer over the small
      immediately presented reinforcer. The delay to the small reinforcer was
      maintained at 6.0 s, but the delay to the large reinforcer was varied among 9.0,
      15.0, 24.0, and 36.0 s in Experiment 2, in which 4 males and 4 females
      participated. Most subjects consistently chose the large increasingly delayed
      reinforcer, although choice for the small 6.0-s delayed reinforcer developed in
      some females when the large reinforcer was delayed for 24.0 or 36.0 s. These
      choice patterns were not predicted from a literal application of a model that
      says choice should favor the alternative correlated with the higher
      (amount/delay) ratio.

PMID- 16812537
TI  - Control of behavior by an establishing stimulus.
AB  - Seventeen pigeons were exposed to a three-key discrete-trial procedure in which a
      peck on the lit center key produced food if, and only if, the left keylight was
      lit. The center key was illuminated by a peck on the lit right key. Of interest
      was whether subjects pecked the right key before or after the response
      independent onset of the left keylight. Pecks on the right key after left
      keylight onset suggest control of behavior by the left keylight-an establishing
      stimulus. In three experiments, the strength of center-keylight onset as
      conditioned reinforcer for a response on the right key was manipulated by
      altering the size of the reduction in time to food delivery correlated with its
      onset. Control of pigeons' key pecks by onset of the left keylight occurred on
      more trials per session when the center keylight was a relatively weak
      conditioned reinforcer and on fewer trials per session when the center keylight
      was a relatively strong condtioned reinforcer. Differences across conditions in
      the degree of control by onset of the establishing stimulus were greatest when
      changes in conditioned reinforcer strength occurred relatively frequently and
      were signaled. The results provide evidence of the function of an establishing
      stimulus.

PMID- 16812538
TI  - Information on response requirements compared with information on food density as
      a reinforcer of observing in pigeons.
AB  - On a variable-interval schedule, pecking the key to the pigeon's right (observing
      response) produced red or green displays relating to the delivery of grain and
      its dependence on pecking the key to the left (food key). During various blocks
      of sessions, mixed (no stimulus change) schedules including the following pairs
      of components were temporarily converted by the observing response to their
      corresponding multiple (correlated stimuli) schedules: variable-interval 60-s,
      extinction; variable-interval 60-s, variable-time (response-independent) 60-s;
      extinction, variable-time 60-s. Differences in food delivery maintained
      substantial rates of responding on the observing key, without regard to pecking
      requirements on the food key. Although stimuli correlated with differences in the
      response requirement on the food key maintained higher observing rates than those
      maintained by uncorrelated stimuli, they were much lower than those based on
      food. The value of predictive stimuli as reinforcers is determined by the value
      of the events predicted. In particular, the cost of pecking appears to be low,
      and this may place limitations on the applicability of energy-based and economic
      models of behavior.

PMID- 16812539
TI  - Changes in functional response units with briefly delayed reinforcement.
AB  - In two experiments, key-peck responding of pigeons was compared under variable
      interval schedules that arranged immediate reinforcement and ones that arranged
      unsignaled delays of reinforcement. Responses during the nominal unsignaled delay
      periods had no effect on the reinforcer presentations. In Experiment 1, the
      unsignaled delays were studied using variable-interval schedules as baselines.
      Relative to the immediate reinforcement condition, 0.5-s unsignaled delays
      decreased the duration of the reinforced interresponse times and increased the
      overall frequency of short (<0.5-s) interresponse times. Longer, 5.0-s unsignaled
      delays increased the duration of the reinforced interresponse times and decreased
      the overall frequency of the short interresponse times. In Experiment 2, similar
      effects to those of Experiment 1 were obtained when the 0.5-s unsignaled delays
      were imposed upon a baseline schedule that explicitly arranged reinforcement of
      short interresponse times and therefore already generated a large number of short
      interresponse times. The results support earlier suggestions that the unsignaled
      0.5-s delays change the functional response unit from a single key peck to a
      multiple key-peck unit. These findings are discussed in terms of the mechanisms
      by which contingencies control response structure in the absence of specific
      structural requirements.

PMID- 16812541
TI  - Quasi-dynamic choice models: Melioration and ratio invariance.
AB  - There is continuing controversy about the behavioral process or processes that
      underlie the major regularities of free-operant choice such as molar matching and
      systematic deviations therefrom. A recent interchange between Vaughan and
      Silberberg and Ziriax concerned the relative merits of melioration, and a
      computer simulation of molecular maximizing. There are difficulties in evaluating
      theories expressed as computer programs because many arbitrary decisions must
      often be made in order to get the programs to operate. I therefore propose an
      alternative form of model that I term quasi-dynamic as a useful intermediate form
      of theory appropriate to our current state of knowledge about free-operant
      choice. Quasi-dynamic models resemble the game-theoretic analyses now commonplace
      in biology in that they can predict stable and unstable equilibria but not
      dynamic properties such as learning curves. It is possible to interpret
      melioration as a quasi-dynamic model. An alternative quasi-dynamic model for
      probabilistic choice, ratio invariance, has been proposed by Horner and Staddon.
      The present paper compares the predictions of melioration and ratio invariance
      for five experimental situations: concurrent variable-interval variable-interval
      schedules, concurrent variable-interval variable-ratio schedules, the two-armed
      bandit (concurrent random-ratio schedules), and two types of frequency-dependent
      schedule. Neither approach easily explains all the data, but ratio invariance
      seems to provide a better picture of pigeons' response to probabilistic choice
      procedures. Ratio invariance is also more adaptive (less susceptible to "traps")
      and closer to the original expression of the law of effect than pure hill
      climbing processes such as momentary maximizing and melioration, although such
      processes may come in to play on more complex procedures that provide
      opportunities for temporal discrimination.

PMID- 16812540
TI  - Choice in transition: A comparison of melioration and the kinetic model.
AB  - Transition-state choice behavior of pigeons was examined in two experiments
      designed to test predictions of melioration and the kinetic model. Both
      experiments began with an initial training condition during which subjects were
      maintained on concurrent variable-interval schedules. In Experiment 1, subjects
      were then exposed to concurrent variable-ratio schedules, whereas in Experiment
      2, subjects were then exposed to concurrent extinction. Contrary to the
      predictions of melioration, but consistent with the kinetic model, acquisition of
      preference on concurrent variable-ratio schedules followed a negatively
      accelerated logistic trajectory, and preference remained stable in concurrent
      extinction. Predictions made by the kinetic model concerning rates of switching
      between alternatives were also supported.

PMID- 16812542
TI  - Criticism and response in the Skinner controversies.

PMID- 16812543
TI  - Maximizing present value: A model to explain why moderate response rates obtain
      on variable-interval schedules.
AB  - In Phases 1 and 3, two Japanese monkeys responded on a multiple variable-ratio 80
      variable-interval X schedule, where the value of X was adjusted to ensure equal
      between-schedule reinforcement rates. Components strictly alternated following
      the delivery of a food pellet, and each session ended following 50 components.
      Phase 2 differed from the others only in that the 50 pellets previously earned
      during the session were delivered together at session's end. Variable-ratio
      response rates did not decrease across phases, but variable-interval response
      rates decreased substantially during the Phase 2 procedure. This rate decrease
      was attributed to the food-at-session's-end manipulation removing the greater
      immediacy of reinforcement provided by short interresponse times relative to long
      interresponse times. Without this time preference for short interresponse times,
      the variable-interval interresponse-time reinforcement feedback function largely
      controlled response emission, dictating a response-rate reduction. This result
      was explained in terms of the economic notion of "maximizing present value."

PMID- 16812544
TI  - Concurrent schedules: Interaction of reinforcer frequency and reinforcer
      duration.
AB  - Six pigeons were trained on concurrent variable-interval schedules with unequal
      reinforcer durations for the two responses. The schedules arranged on the two
      keys were kept equal while they were varied in absolute size. As the overall
      reinforcer rate was increased, both response-allocation and time-allocation
      measures of choice showed a trend toward indifference, and measures of
      sensitivity to reinforcer-duration ratios significantly decreased. Recent reports
      have shown that the generalized matching law cannot describe the changes in
      behavior allocation under constant delay-, duration-, or rate-ratios when changes
      are made in the absolute levels of each of these variables. The present results
      complement these findings by demonstrating that the concatenated generalized
      matching law cannot describe the interactions of two reinforcer variables on
      behavior allocation.

PMID- 16812545
TI  - Concurrent-chain performance: Effects of absolute and relative terminal-link
      entry frequency.
AB  - Six pigeons were trained in a concurrent-chain procedure with constant variable
      interval 6-s variable-interval 12-s terminal links. Five groups of conditions
      were arranged. Within a group of conditions, the duration of one initial-link
      schedule was held constant and the duration of the other initial link was varied.
      The duration of the varied initial link was always longer than, or equal to, the
      constant initial-link duration. The duration of the shorter initial link was
      varied across groups of conditions from 5 s to 70 s. The data from each group
      were well described by the generalized matching law. Sensitivity (a) to the
      terminal-link entry ratio increased as the shorter initial-link duration
      increased, but appeared to reach an asymptote at shorter initial-link durations
      greater than 32 s. Terminal-link bias did not change with changes in shorter
      initial-link duration for the response-allocation data, but showed a small
      increase with increasing shorter initial-link duration for the time-allocation
      data.

PMID- 16812546
TI  - The effects of a variety of instructions on human fixed-interval performance.
AB  - College students were instructed to press a button for points under a single
      reinforcement schedule or under a variety of reinforcement schedules.
      Instructions for a single schedule were either specific or minimal. Instructions
      on a variety of schedules involved specific instructions on eight different
      schedules of reinforcement. Subsequent to the varied training, responding under a
      fixed-interval schedule occurred at a low rate. Both the minimal and specific
      instruction training led to fixed-interval responding that was similar to the
      responding exhibited during training. These findings suggest that under certain
      conditions instructed behavior is sensitive to changes in contingencies.

PMID- 16812547
TI  - A test of symmetry and transitivity in the conditional discrimination
      performances of pigeons.
AB  - In a matching-to-sample context, pigeons were taught two conditional
      discriminations according to one of three equivalence paradigms: train if A, then
      select B and if B, then select C; train if B, then A and if B, then C; or train
      if A, then B and if C, then B. Test trials without reinforcement revealed that
      the conditional relations did not satisfy the symmetrical and transitive
      properties of an equivalence relation. Apparently, only specific if... then
      relations were learned. Contrary to Kendall's (1983) findings, and probably as a
      consequence of procedural differences, none of the pigeons in the present
      experiment were observed to emit mediating behavior during the transitivity probe
      trials. The absence of symmetry and transitivity may be related to the individual
      stimuli not being reflexive. Behavioral techniques other than the commonly used
      matching-to-sample technique might better succeed in avoiding unintended stimulus
      control in the study of the formation of stimulus classes.

PMID- 16812548
TI  - Responding of pigeons under variable-interval schedules of unsignaled, briefly
      signaled, and completely signaled delays to reinforcement.
AB  - In Experiment 1, three pigeons' key pecking was maintained under a variable
      interval 60-s schedule of food reinforcement. A 1-s unsignaled nonresetting delay
      to reinforcement was then added. Rates decreased and stabilized at values below
      those observed under immediate-reinforcement conditions. A brief stimulus change
      (key lit red for 0.5 s) was then arranged to follow immediately the peck that
      began the delay. Response rates quickly returned to baseline levels.
      Subsequently, rates near baseline levels were maintained with briefly signaled
      delays of 3 and 9 s. When a 27-s briefly signaled delay was instituted, response
      rates decreased to low levels. In Experiment 2, four pigeons' responding was
      first maintained under a multiple variable-interval 60-s (green key) variable
      interval 60-s (red key) schedule. Response rates in both components fell to low
      levels when a 3-s unsignaled delay was added. In the first component delays were
      then briefly signaled in the same manner as Experiment 1, and in the second
      component they were signaled with a change in key color that remained until food
      was delivered. Response rates increased to near baseline levels in both
      components, and remained near baseline when the delays in both components were
      lengthened to 9 s. When delays were lengthened to 27 s, response rates fell to
      low levels in the briefly signaled delay component for three of four pigeons
      while remaining at or near baseline in the completely signaled delay component.
      In Experiment 3, low response rates under a 9-s unsignaled delay to reinforcement
      (tandem variable-interval 60 s fixed-time 9 s) increased when the delay was
      briefly signaled. The role of the brief stimulus as conditioned reinforcement may
      be a function of its temporal relation to food, and thus may be related to the
      eliciting function of the stimulus.

PMID- 16812549
TI  - Concurrent variable-ratio schedules: Implications for the generalized matching
      law.
AB  - Rats' responses were reinforced on concurrent variable-ratio variable-ratio
      schedules in which responses on one lever incremented the ratio counter and
      responses on a second lever changed the schedule and correlated stimulus. The
      relative frequency of reinforcement was varied from .10 to .99. In one set of
      conditions, responding on the main lever incremented both ratio counters, but
      reinforcement required a response in the presence of the stimulus correlated with
      the ratio that had been completed. In a second set of conditions, responses on
      the main lever incremented only the ratio correlated with the stimulus that was
      currently present. When main-lever responses incremented both ratio counters,
      subjects distributed responding and time in a manner consistent with the
      generalized matching law. When responses on the main lever incremented only the
      schedule currently in effect, the rats responded almost exclusively on the
      schedule producing the higher frequency of reinforcement. These results extend
      the applicability of the generalized matching law to dependent ratio schedules.

PMID- 16812550
TI  - Determinants of pausing under variable-ratio schedules: Reinforcer magnitude,
      ratio size, and schedule configuration.
AB  - Pigeons pecked a key under two-component multiple variable-ratio schedules that
      offered 8-s or 2-s access to grain. Phase 1 assessed the effects of differences
      in reinforcer magnitude on postreinforcement pausing, as a function of ratio
      size. In Phase 2, postreinforcement pausing and the first five interresponse
      times in each ratio were measured as a function of differences in reinforcer
      magnitude under equal variable-ratio schedules consisting of different
      configurations of individual ratios. Rates were also calculated exclusive of
      postreinforcement pause times in both phases. The results from Phase 1 showed
      that as ratio size increased, the differences in pausing educed by unequal
      reinforcer magnitudes also increased. The results of Phase 2 showed that the
      effects of reinforcer magnitude on pausing and IRT durations were a function of
      schedule configuration. Under one configuration, in which the smallest ratio was
      a fixed-ratio 1, pauses were unaffected by magnitude but the first five
      interresponse times were affected. Under the other configuration, in which the
      smallest ratio was a fixed-ratio 7, pauses were affected by reinforcer magnitude
      but the first five interresponse times were not. The effect of each configuration
      seemed to be determined by the value of the smallest individual ratio. Rates
      calculated exclusive of postreinforcement pause times were, in general, directly
      related to reinforcer magnitude, and the relation was shown to be a function of
      schedule configuration.

PMID- 16812552
TI  - Finding the philosophical core: A review of Stephen C. Pepper's World Hypotheses:
      A Study in Evidence.

PMID- 16812551
TI  - Behavioral stereotypy and the generalized matching equation.
AB  - The development of behavioral stereotypy is a common result of exposure to both
      response-dependent and response-independent reinforcement procedures. The
      generalized matching equation and two dynamic versions of that equation, which
      take into account the time differential between reinforcements and their effect
      on behavior, predict this outcome of many procedures involving reinforcement.
      Following from the assumption that distinct response topographies, distinct
      response sequences, or orientations to distinct stimuli can be treated in the
      equations as distinct classes of behavior, the equations predict that-at least
      for matching and undermatching-the behavior class that is most biased relative to
      other behavior classes of the same type will tend to predominate to the exclusion
      or near exclusion of those behavior classes.

PMID- 16812553
TI  - Is there a decisive test between matching and maximizing?
AB  - Reinforcers under typical concurrent variable-interval, variable-ratio schedules
      may be (a) earned and obtained during the variable-interval component, (b) earned
      and obtained during the variable-ratio component, or (c) earned during the
      variable-ratio component and obtained during the variable-interval component.
      Categories a and b, which have no bearing on matching versus maximizing accounts
      of choice, were set at zero. The rate of Category c reinforcers and the duration
      of a changeover delay were varied. Simple matching, which predicts exclusive
      choice of the variable-interval component, and strict maximizing of overall
      reinforcement rate, which predicts a bias towards the variable-ratio component,
      were both disconfirmed: Subjects spent approximately 25% of their time in the
      variable-ratio component, contrary to the matching prediction, but earned only
      about one third of the reinforcers predicted by strict maximizing. However,
      maximizing describes the findings functionally in terms of discounting of delayed
      reinforcers; matching may describe the data in terms of a restructuring of the
      alternatives. Matching and maximizing are not competing theories about the
      fundamental nature of choice, but compatible points of view that may reveal
      environmental function and behavioral structure.

PMID- 16812554
TI  - Transfer of a conditional ordering response through conditional equivalence
      classes.
AB  - Eight adult humans were taught conditional discriminations in a matching-to
      sample format that led to the formation of two four-member equivalence classes.
      When subjects were taught to select one comparison stimulus from each class in a
      set order, they then ordered all other members of the equivalence classes without
      explicit training. When the ordering response itself was brought under
      conditional control, conditional sequencing also transferred to all other members
      of the two equivalence classes. When the conditional discriminations in the
      matching-to-sample task were brought under higher order conditional control, the
      eight stimulus members were arranged into four conditional equivalence classes.
      Both ordering and conditional ordering transferred to all members of the four
      conditional equivalence classes; for some subjects this occurred without a
      typical test for equivalence. One hundred twenty untrained sequences emerged from
      eight trained sequences for all subjects. Transfer of functions through
      equivalence classes may contribute to a behavior-analytic approach to semantics
      and generative grammar.

PMID- 16812555
TI  - Choice in the repeated-gambles experiment.
AB  - Humans chose 10 times between two roulette wheels projected on a monitor. During
      the first trial, the left wheel provided a hypothetical $100 with p = .94, and
      the right wheel provided $250 with p = .39. A titration procedure adjusted the
      probability of a $250 win across trials to permit estimation of an indifference
      point between alternatives. In Experiment 1, intertrial-interval duration (25 vs.
      90 s) and whether sessions began with an intertrial interval or a trial were
      varied in a 2 x 2 design in this risky-choice procedure. Risk aversion
      (preference for the $100 wheel) increased with intertrial interval but was
      unaffected by whether sessions began with a trial or an intertrial interval. In
      Experiment 2, all sessions began with a trial, and subjects were informed that
      the experiment ended after 10 trials. Intertrial-interval duration had no effect
      on choice. In Experiment 3, intertrial-interval duration and whether subjects
      were given $10 or $10,000 before beginning were varied among four groups in a 2 x
      2 design. In all other ways, the procedure was unchanged from Experiment 2.
      Intertrial interval had no effect on choice, but the $10,000 groups showed less
      risk aversion than the $10 groups. These results can be explained more readily in
      terms of Kahneman and Tversky's (1984) notion of "framing of the prospect" than
      in terms of Rachlin, Logue, Gibbon, and Frankel's (1986) behavioral account of
      risky choice.

PMID- 16812556
TI  - Typical delay determines waiting time on periodic-food schedules: Static and
      dynamic tests.
AB  - Pigeons and other animals soon learn to wait (pause) after food delivery on
      periodic-food schedules before resuming the food-rewarded response. Under most
      conditions the steady-state duration of the average waiting time, t, is a linear
      function of the typical interfood interval. We describe three experiments
      designed to explore the limits of this process. In all experiments, t was
      associated with one key color and the subsequent food delay, T, with another. In
      the first experiment, we compared the relation between t (waiting time) and T
      (food delay) under two conditions: when T was held constant, and when T was an
      inverse function of t. The pigeons could maximize the rate of food delivery under
      the first condition by setting t to a consistently short value; optimal behavior
      under the second condition required a linear relation with unit slope between t
      and T. Despite this difference in optimal policy, the pigeons in both cases
      showed the same linear relation, with slope less than one, between t and T. This
      result was confirmed in a second parametric experiment that added a third
      condition, in which T + t was held constant. Linear waiting appears to be an
      obligatory rule for pigeons. In a third experiment we arranged for a
      multiplicative relation between t and T (positive feedback), and produced either
      very short or very long waiting times as predicted by a quasi-dynamic model in
      which waiting time is strongly determined by the just-preceding food delay.

PMID- 16812557
TI  - Delay of reinforcers in a concurrent-chain schedule: An extension of the
      hyperbolic-decay model.
AB  - Six pigeons were trained in concurrent-chain schedules with equal aperiodic
      initial links and delays to reinforcers in the terminal links. The terminal links
      always lasted 30 s. In Experiment 1, two reinforcers were delivered in each
      terminal link, with the first reinforcer delivered either 1 s (Experiment 1A) or
      5 s (Experiment 1B) after choice. In these experiments, the delay between the
      first and second reinforcers in one terminal link was 10 s, and the delay between
      the first and second reinforcers on the other key was varied. This variation
      produced little change in preference. In Experiment 1C, the first and second
      delays on one key were 10 s, and on the other key they were varied within the
      restriction that the sum of delays was 20 s. Preference for the varied terminal
      link increased as the first delay was decreased. A hyperbolic model of the value
      of reinforcer delay provided a good description of the data from Experiment 1. In
      Experiment 2, a single reinforcer was delivered in each terminal link after a
      delay of either 0.2 or 19.8 s, and these delays were reversed between conditions.
      The initial-link schedule providing terminal-link access was varied from means of
      5 s to 480 s. As the initial-link duration was increased, preference for the
      shorter delay became less extreme. An extension of the hyperbolic-decay model, in
      which the decay constant was a hyperbolic function of the initial-link duration,
      described the results well. Differences between the procedure used here (constant
      duration terminal links) and that used in conventional concurrent-chain research
      precludes use of the model as a general account of concurrent-chain performance.

PMID- 16812558
TI  - Effects of alternative reinforcement sources: A reevaluation.
AB  - The effects of two alternative sources of food delivery on the key-peck
      responding of pigeons were examined. Pecking was maintained by a variable
      interval 3-min schedule. In the presence of this schedule in different
      conditions, either a variable-time 3-min schedule delivering food independently
      of responding or an equivalent schedule that required a minimum 2-s pause between
      a key peck and food delivery (a differential-reinforcement-of-other-behavior
      schedule) was added. The differential-reinforcement-of-other-behavior schedule
      reduced response rates more than did the variable-time schedule in most
      instances. The delay between a key peck and the next reinforcer consistently was
      longer under the differential-reinforcement-of-other-behavior schedule than under
      the variable-time schedule. Response rates and median delay between responses and
      reinforcers were negatively correlated. These results contradict earlier
      conclusions about the behavioral effects of alternative reinforcement. They
      suggest that an interpretation in terms of response-reinforcer contiguity is
      consistent with the data.

PMID- 16812559
TI  - Vertical jumping and signaled avoidance.
AB  - This paper reports an experiment intended to demonstrate that the vertical
      jumping response can be learned using a signaled-avoidance technique. A
      photoelectric cell system was used to record the response. Twenty female rats,
      divided equally into two groups, were exposed to intertrial intervals of either
      15 or 40 s. Subjects had to achieve three successive criteria of acquisition: 3,
      5, and 10 consecutive avoidance responses. Results showed that both groups
      learned the avoidance response, requiring increasingly larger numbers of trials
      as the acquisition criteria increased. No significant effect of intertrial
      interval was observed.

PMID- 16812560
TI  - The Behavior of Organisms as work in progress.

PMID- 16812561
TI  - Review of B. F. Skinner's The Behavior of Organisms.
AB  - As I reread my review nearly 50 years later, I think of the circumstances. I had
      heard a paper by Fred at the Ithaca meeting of the APA in 1932, and recall the
      praise by Edna Heidbreder, who was sitting next to me, whose remark was that "He
      has a clean mind." The year before his book appeared, I had already cited eight
      of his published papers in a review of the conditioned response in relation to
      conventional learning experiments that appeared in the Psychological Bulletin
      (1937, 34, 61-102). It may be because of that the editor sent me Fred's book to
      review.When I received the copy of his new book to review, I read it carefully,
      and soon reported on it orally before Lewis Terman's weekly seminar to get
      comments and questions before revising my review. I was pleased by Terman's
      excitement over the originality of Fred's approach.

PMID- 16812562
TI  - In the beginning.

PMID- 16812563
TI  - Behavior analysis: The third branch of Aristotle's physics.

PMID- 16812564
TI  - The reflex reserve.

PMID- 16812565
TI  - Inhibition: A cautionary tale.

PMID- 16812566
TI  - Differentiating the behavior of organisms.

PMID- 16812568
TI  - Behavior analysis and biological factors.

PMID- 16812567
TI  - Preface to the behavior of organisms.

PMID- 16812569
TI  - Signaled avoidance in the eye withdrawal reflex of the green crab.
AB  - Learning in a signaled avoidance procedure was studied in the eye withdrawal
      reflex of the green crab, Carcinus maenas. A puff of air to the eye, which causes
      eye retraction, was used as the unconditioned stimulus (US). A mild vibration on
      the carapace, which has no effect on untrained animals, was used as a warning
      (conditioned) stimulus (CS). Eye withdrawal during the CS led to the omission of
      the otherwise scheduled US. Acquisition was rapid, reaching about 75% avoidance
      after 30 trials. Extinction occurred slowly over the course of 40 CS-only trials.
      Yoked controls did not perform as well. The behavior of experimental animals in
      the avoidance procedure was found to be essentially identical to the performance
      of animals subjected to a classical conditioning paradigm in which CS responses
      had no effect on US presentation. Additional groups of animals were subjected to
      experiments in which (a) avoidance conditioning (60 trials) was followed by
      classical conditioning (40 trials) or (b) classical conditioning was followed by
      avoidance. The behavior of these groups was, again, essentially identical. The
      results suggest that there may be an underlying Pavlovian mechanism for the
      learned response, although the contribution of an operant process is not
      excluded. The results expand the range of invertebrate animals in which
      fundamental conditioning phenomena can be demonstrated, and may provide a
      neuronal model for learning in a signaled avoidance procedure.

PMID- 16812570
TI  - Discrimination learning in a foraging situation.
AB  - Rats were allowed to forage in a simulated natural environment made up of eight
      food sources (patches) each containing a fixed number of pellets. Two of the
      eight contained an extra supply of peanuts. The peanut patches were signaled by
      an olfactory/visual cue located at the bottom of the ladder leading to the patch.
      In successive phases the number of sessions per day, height of the patches, and
      availability of peanuts were manipulated. Subjects showed evidence of
      discrimination learning under these conditions, although the degree of
      discriminatory behavior varied as a function of environmental manipulations.
      Assessment of behavior within foraging sessions showed that subjects
      systematically changed their patterns of utilization of patches across time.
      Sampling or exploration, as well as food reinforcement, seem implicated in these
      results.

PMID- 16812571
TI  - Pigeons can discriminate locations presented in pictures.
AB  - The present experiments were designed to teach pigeons to discriminate two
      locations represented by color photographs. Two sets of photographs were taken at
      two distinctive locations on a university campus. These sets represented several
      standpoints at each location. For the true-discrimination group, pictures from
      the two locations were differentially associated with reward; for the
      pseudodiscrimination group, half of the views from each location were arbitrarily
      but consistently associated with reward. The former group acquired the
      discrimination much more rapidly. These birds also showed good transfer to new
      views from the standpoints used in training and to a new standpoint at each
      location not used in training. In a second experiment, another group of pigeons
      could terminate any training trial by pecking an "advance" key. Three of 4
      subjects used this option to reduce the duration of trials in which pictures from
      the negative location were presented. These data suggest that pigeons can
      integrate views shown in pictures into a "concept" of a location. The method used
      here may be the experimental analogue of a common, natural process by which
      animals learn to identify locations.

PMID- 16812572
TI  - Comprehension of "absence" by an African Grey parrot: Learning with respect to
      questions of same/different.
AB  - An African Grey parrot, Alex, learned to report on the absence or presence of
      similarity and difference between two objects. Alex was shown pairs of objects
      that were (a) totally dissimilar, (b) identical, or (c) similar or different with
      respect to one of three attributes (color, shape, or material). In the first two
      cases, he responded to the respective queries of "What's same?" or "What's
      different?" with the vocalization "none," and in the third case he responded with
      the appropriate category label ("color," "shape," or "mah-mah" [matter]). His
      accuracy was 80.9% to 83.9% for pairs of familiar objects not used in training
      and 72.5% to 78.4% for pairs whose colors, shapes, and materials were unfamiliar.
      The data provide evidence that this parrot's abilities are comparable to those of
      mammals that have been trained to report on the presence or absence of objects or
      features of objects.

PMID- 16812573
TI  - Response-reinforcer dependency location in interval schedules of reinforcement.
AB  - In five experiments we studied the effects on pigeons' key pecking of the
      location of four or more successive response-dependent reinforcers imbedded in a
      schedule arranging otherwise response-independent reinforcers. In Experiment 1,
      high local response rates early in the session were extended farther into the
      session as the number of response-dependent reinforcers at the beginning of the
      session increased. A block of four successive response-dependent reinforcers then
      was scheduled at the beginning, middle, or end of the session (Experiment 2)
      resulting in higher local response rates at those times in the session when the
      response-dependent reinforcers were arranged. When placed in random locations in
      successive sessions (Experiment 3), uniform local rates occurred throughout the
      session. In Experiments 1, 2, and 3, delivery of the remaining response
      independent reinforcers was precluded until the response-dependent reinforcers
      were collected. Experiment 4 was similar to Experiments 1 and 2, except that all
      response-independent reinforcers occurred irrespective of whether the response
      dependent reinforcers had been collected. This yielded results similar to those
      obtained in the first two experiments. In Experiment 5, responding early in the
      session had no consequence other than allowing access to the schedule of response
      independent food delivery. As in the first experiment, local rates generally were
      higher early in the session. The results indicate that the location of response
      reinforcer dependencies precisely control behavior and that such effects often
      are not captured by descriptions of behavior in terms of overall response rates.

PMID- 16812574
TI  - A quantitative analysis of chain-schedule performance.
AB  - Six pigeons were trained with a chain variable-interval variable-interval
      schedule on the left key and with reinforcers available on the right key on a
      single variable-interval schedule arranged concurrently with both links of the
      chain. All three schedules were separately and systematically varied over a wide
      range of mean intervals. During these manipulations, the obtained reinforcer
      rates on constant arranged schedules also frequently changed systematically.
      Increasing reinforcer rates in Link 2 of the chain increased response rates in
      both links and decreased response rates in the variable-interval schedule
      concurrently available with Link 2. Increasing Link-1 reinforcer rates increased
      Link-1 response rates and decreased Link-2 response rates. Increasing reinforcer
      rates on the right-key schedule decreased response rates in Link 1 of the chain
      but did not affect the rate in Link 2. The results extend and amplify previous
      analyses of chain-schedule performance and help define the effects that a
      quantitative model must describe. However, the complexity of the results, and the
      fact that constant arranged reinforcer schedules did not necessarily lead to
      constant obtained reinforcer rates, precluded a quantitative analysis.

PMID- 16812575
TI  - The development of adaptive choice in a self-control paradigm.
AB  - Sixteen girls (ages 4, 6, 9, and 12) performed on concurrent-chain schedules of
      reinforcement. The initial links were variable-interval 10-s schedules, and the
      terminal links offered a long delay (20, 30, 40, or 50 s) followed by two tokens
      or a short delay (10 s) followed by one token. Tokens were used to buy toys and
      sweets. The effect of increasing the delay to the large reward differed
      significantly across age groups. Whereas 6- and 9-year-olds maintained a strong
      preference for the larger, more delayed reward under all delay conditions, half
      of the 4-year-olds and all the 12-year-olds showed increasing preference for the
      small reward as the delay to the large reward increased. The results suggest a
      two-stage account of the development of self-control. In the first stage,
      behavior is increasingly controlled by reward size, as children learn how to wait
      for delayed rewards, and in the second phase behavior is increasingly controlled
      by reward rate, as children learn when it is in fact profitable to wait.

PMID- 16812576
TI  - Children's choice: Sensitivity to changes in reinforcer density.
AB  - Two experiments were carried out in which children's sensitivity to changes in
      reinforcer density (number of reinforcers per session) was measured in a choice
      paradigm. In Experiment 1, 24 girls (ages 6, 9, and 12 years) performed on
      concurrent-chain schedules of reinforcement. The initial links were variable
      interval 10-s schedules. One terminal link always gave three tokens after 30 s,
      but the parameters associated with the other were varied. Independent
      manipulations of reinforcer size (two tokens or four tokens) and prereinforcement
      delay (25 s or 65 s) led to equal changes in the relative density of tokens that
      could be earned on the schedules. Subjects at all ages were sensitive to changes
      in reinforcer density brought about by changes in reinforcer size, whereas only 3
      12-year-olds showed sensitivity to the changes brought about by manipulation of
      prereinforcer delay. In Experiment 2, titration procedures were used to test the
      extent of this insensitivity to delay in 32 6- and 12-year-old children. In these
      procedures, a repeated choice of the large reinforcer increased the delay to its
      delivery, and a repeated choice of the small reinforcer reduced the delay to the
      delivery of the large reinforcer. Whereas 6-year-old boys and girls tended to
      maintain a strong preference for the large reinforcer, so increasing the delay to
      its delivery, 12-year-olds tended to distribute their responses to both
      alternatives, thus producing a stable level of delay to the large reinforcer. The
      results from the two experiments support the idea of two stages in the
      development of adaptive intertemporal choice.

PMID- 16812577
TI  - Sensitivity of time allocation to an overall reinforcer rate feedback function in
      concurrent interval schedules.
AB  - Six pigeons were trained on concurrent variable-interval schedules in which
      feedback functions arranged that the overall reinforcer rate either (a) was
      independent of preference, (b) decreased with increasing absolute preference, or
      (c) increased with increasing absolute preference. In Experiment 1, the
      reinforcer rate in an interreinforcement interval was determined by the absolute
      time-allocation ratio in the previous interval. When arranged reinforcer ratios
      were varied, there was no evidence of control over preference by overall
      reinforcer rate. In Experiment 2, the feedback function arranged that reinforcer
      rates were an inverse function of absolute preference, and window durations were
      fixed times. In Phase 1, using schedules that provided a four-to-one reinforcer
      ratio, the window duration was decreased from 20 s to 5 s over four conditions.
      Then, in Phases 2 and 3, the arranged reinforcer ratios were varied. In Phase 2,
      the reinforcer rate in the current 5-s time window was determined by preference
      in the previous 5-s window, and in Phase 3, the window durations were 20 s.
      Again, there was no indication of control by obtained overall reinforcer rate.
      These data call into question theories that suggest that the process underlying
      matching is one of maximizing overall reinforcer rates, or that preference in
      concurrent aperiodic schedules is controlled to any extent by overall reinforcer
      rate. They also question the notion that concurrent-schedule preference is
      controlled by molecular maximizing.

PMID- 16812578
TI  - Choice and terminal-link response topography.
AB  - Six pigeons responded under concurrent-chains schedules. For 3 birds, pecking was
      required in both initial links; for 3 others, treadle pressing was required. For
      all subjects, pecking was required in one terminal link and treadling in the
      other. The initial links consisted of independent variable-interval 60-s
      schedules. All birds were exposed to five pairs of terminal-link variable
      interval schedules over 10 conditions: 6 s versus 54 s, 18 s versus 42 s, 30 s
      versus 30 s, 42 s versus 18 s, and 54 s versus 6 s. Comparisons of responding
      under nominally identical terminal-link variable-interval schedules showed that,
      without exception, higher choice proportions were obtained for the alternative
      correlated with terminal-link pecking. Moreover, terminal-link delay to
      reinforcement was shorter for terminal-link pecking than for terminal-link
      treadling chains. This factor, along with response force requirements, was
      implicated in explaining the present as well as previous findings of preference
      for pecking over treadling. It was found also that the delay-reduction hypothesis
      provided only a moderately accurate description of performance under concurrent
      chains in which different terminal-link response topographies are required. These
      findings suggest that quantitative models neglecting the effects of differing
      terminal-link topographies may be incomplete.

PMID- 16812579
TI  - Discrimination theory of rule-governed behavior.
AB  - In rule-governed behavior, previously established elementary discriminations are
      combined in complex instructions and thus result in complex behavior.
      Discriminative combining and recombining of responses produce behavior with
      characteristics differing from those of behavior that is established through the
      effects of its direct consequences. For example, responding in instructed
      discrimination may be occasioned by discriminative stimuli that are temporally
      and situationally removed from the circumstances under which the discrimination
      is instructed. The present account illustrates properties of rule-governed
      behavior with examples from research in instructional control and imitation
      learning. Units of instructed behavior, circumstances controlling compliance with
      instructions, and rule-governed problem solving are considered.

PMID- 16812580
TI  - Effects of relative reinforcer frequency on complex color detection.
AB  - Pigeons were trained under a discrete-trials detection procedure in which one of
      a set of color stimuli was presented on the center key and a single response
      turned off the stimulus and illuminated two side keys. Single responses to one or
      the other side key produced occasional reinforcers depending on the value of the
      color stimulus. In Experiment 1, one color-stimulus set comprised 559, 564, 569,
      and 574 nm, and right-key pecks were occasionally reinforced following
      presentations of members of this set. The other stimulus set comprised 579, 584,
      589, and 594 nm, and left-key pecks were occasionally reinforced following
      presentations of members of this set. Across seven experimental conditions, the
      left/(left + right) relative reinforcer frequency was varied from .1 to .9. In
      Experiment 2, one stimulus set contained only one member, 574 nm, and right-key
      responses were occasionally reinforced following its presentation. Over 12
      experimental conditions, two manipulations were carried out. First, the number of
      stimuli comprising the other stimulus set was increased from one (579 nm) to two
      (579 and 584 nm) to three (579, 584, and 589 nm) and to four (579, 584, 589, and
      594 nm), and left-key responses were reinforced occasionally following center-key
      presentations of members of this set. Second, for each stimulus combination, the
      left/(left + right) relative reinforcer frequency was varied from .1 to .5 to .9
      across three experimental conditions. The principal finding of Experiments 1 and
      2 was that reinforcers and stimuli interacted in their effects on behavior. In
      Experiment 3, pairs of adjacent stimuli (5 nm apart) in the range 559 to 594 nm
      were presented in each experimental condition, and the left/(left + right)
      relative reinforcer frequency was held constant at .5. The data from all three
      experiments were analyzed according to a detection model describing performance
      in multiple-stimulus two-response procedures. This model provided independent
      measures of stimulus discriminability, contingency discriminability, and bias.
      The analysis showed that (a) consistent with the color-naming function, pigeons
      were better able to discriminate between higher nanometer values than lower
      nanometer values; (b) their ability to discriminate between the stimuli was
      independent of the number of wavelengths comprising each stimulus set; (c) they
      allocated delivered reinforcers very accurately to the previously emitted
      response; and (d) no consistent biases emerged.

PMID- 16812581
TI  - Psychological distance to reward: A human replication.
AB  - Choice behavior in college students was examined in two experiments using the
      concurrent-chains procedure. In both experiments, the concurrent chains were
      presented on a microcomputer in the form of an air-defense game in which subjects
      used two radar systems to detect and subsequently destroy enemy aircraft. Access
      to one of two radar systems was controlled by a pair of independent concurrent
      variable-interval 60-s schedules with a 4-s changeover delay always in effect. In
      the terminal link, the appearance of an enemy aircraft was determined by a pair
      of differentially segmented fixed-time schedules (Experiment 1) or fixed-interval
      schedules (Experiment 2) of equal overall duration. In Experiment 1, the terminal
      link duration was either 20 s or 40 s, and subjects preferred the unsegmented to
      the segmented intervals. In Experiment 2, the duration was either 10 s or 60 s,
      and the reinforcement contingencies required responding during the terminal link.
      Prior to the reinstatement of the initial link, subjects estimated the duration
      of the terminal-link schedule. Segmentation affected choice in the 60-s
      conditions but not in the 10-s ones. Preference for the unsegmented schedule was
      correlated with an overestimation of the durations for the segmented schedules.
      These results replicated those found in animal experiments and support the notion
      of increasing the psychological distance to reward by segmenting a time-based
      schedule of reinforcement.

PMID- 16812582
TI  - The speaker as listener.
AB  - This study reports the results of an experiment with 4 female 5-year-old
      children, in which the verbal behavior of the children (talking to themselves)
      was studied under two conditions-an anthropomorphic toy condition and a
      nonanthropomorphic toy condition. The anthropomorphic condition consisted of
      three-dimensional toys such as dolls, stuffed animals, and figurines. The
      nonanthropomorphic toy condition consisted of two-dimensional materials such as
      puzzles, coloring books, and story books. The independent variables were the toy
      conditions. The dependent variables were verbal-behavior units; these included
      mands, tacts, intraverbals, autoclitics, and conversational units. The conditions
      were compared using a multiple schedule design. The results showed that more
      total units occurred in the anthropomorphic toy condition than in the
      nonanthropomorphic toy condition and that conversational units occurred in the
      anthropomorphic condition only. Consistent with Skinner's (1957) hypothesis, the
      children acted as both speaker and listener when emitting verbal behavior to
      themselves in the anthropomorphic condition.

PMID- 16812583
TI  - Correspondence in children's self-report: Tacting and manding aspects.
AB  - Four boys and 4 girls (3 to 5 years old) played with as many as three toys chosen
      from a set of six, and were then asked whether they played with each of the toys.
      After a baseline in which all children showed high levels of correspondence
      between reported and actual behavior, reports of play were differentially
      reinforced, first in an individual and then in a social context. Two children in
      the individual condition began to report play with all six toys, even though no
      more than three toys had been played with. When reports of play were reinforced
      in a group context, 5 children reported play with all six toys. When
      correspondence was subsequently reinforced, virtually complete correspondence
      returned and was maintained in a third noncontingent reinforcement condition.
      Correspondence and lack of correspondence were discussed in terms of self-tacting
      and distorted tacting or manding.

PMID- 16812584
TI  - Transfer of contextual stimulus function via equivalence class development.
AB  - In a conditional discrimination, 6 college students arranged six Cyrillic letters
      into groups of three based upon which of two additional Cyrillic letters
      (contextual stimuli) was present. All subjects demonstrated symmetry and
      transitivity within each class of equivalent stimuli. In a second conditional
      discrimination, two more Cyrillic letters were related to each contextual
      stimulus. Testing of symmetrical and transitive relations between the original
      contextual stimulus and the two new ones confirmed the development of two three
      member classes of contextual stimuli. Subsequent tests demonstrated that the new
      contextual stimuli controlled the previously trained sample-comparison relations
      for all subjects.

PMID- 16812585
TI  - Nonhumans have not yet shown stimulus equivalence.
AB  - Recently, two published articles have reported finding stimulus equivalence in
      nonhumans. One suggested that equivalence was due to the mediation of names. The
      procedure used trained all components of all tested relations. Because nothing
      was derived, the defining characteristics of equivalence were not achieved. In
      the second study a definition of equivalence was proposed that fails to
      distinguish functional stimulus classes from equivalence classes. The resulting
      data are not clearly relevant to stimulus equivalence in Sidman's sense of the
      term. Stimulus equivalence has not yet been shown in nonhumans.

PMID- 16812586
TI  - Reply to saunders and to hayes.

PMID- 16812587
TI  - Reply to hayes.

PMID- 16812588
TI  - Algorithmic shaping and misbehavior in the acquisition of token deposit by rats.
AB  - In two experiments, rats were trained to deposit ball bearings down a hole in the
      floor, using an algorithmic version of shaping. The experimenter coded responses
      expected to be precursors of the target response, ball bearing deposit; a
      computer program reinforced these responses, or not, according to an algorithm
      that mimicked the processes thought to occur in conventional shaping. In the
      first experiment, 8 of 10 rats were successfully shaped; in the second, 5 of 5
      were successfully shaped, and the median number of sessions required was the same
      as for a control group trained using conventional shaping. In both experiments,
      "misbehavior," that is, excessive handling and chewing of the ball bearings, was
      observed, and when the algorithmic shaping procedure was used, misbehavior could
      be shown to occur in spite of reduced reinforcement for the responses involved.

PMID- 16812589
TI  - Income maximizing in concurrent interval-ratio schedules.
AB  - Three mice chose between concurrent variable-ratio variable-interval schedules to
      produce a warm air stream while they were housed in a cold chamber. Across
      conditions, the duration of the warm air stream was varied between 10 and 80 s
      and was equal for both schedules. Preference for the VI schedule covaried with
      reinforcer duration as predicted by maximizing accounts of choice.

PMID- 16812590
TI  - Stochastic choice models: A comparison between Bush-Mosteller and a source
      independent reward-following model.
AB  - Horner and Staddon (1987) argued that a class of reward-following processes
      defined by a property they termed ratio invariance is a better model for the
      probabilistic choice performance of pigeons than competing molecular accounts
      such as momentary maximizing, melioration, and the Bush-Mosteller model. The
      critical data were provided by choice distributions-distributions of a variable
      S, the proportion of Right choices, defined on a moving window typically 32
      choices long-obtained under a frequency-dependent schedule. The schedule
      prescribed equal payoff probabilities, p(S), for both choices. p(S) was a maximum
      when S = 0.5 and declined linearly for S values above and below 0.5. Pigeons
      showed generally bimodal choice distributions with the modes at equal p(S)
      values. These data do not follow easily from melioration or momentary maximizing
      and are inconsistent with molar maximizing, but they may be consistent with Bush
      Mosteller. We present here the results of computer simulations showing that the
      ratio-invariance model studied yields, as expected, choice modes at equal p(S)
      values, but that Bush-Mosteller, although capable of generating bimodal choice
      distributions, does not have choice modes at equal p(S) values.

PMID- 16812592
TI  - Speaking of behavior.

PMID- 16812591
TI  - The effect of logarithmic transformation on estimating the parameters of the
      generalized matching law.
AB  - The generalized matching law was initially stated as a nonlinear relation between
      reinforcement-rate ratios and response-rate ratios. Often, the variables of the
      law are transformed logarithmically to remove the nonlinearity; empirical results
      are then fit to the model through least-squares regression. However, the
      logarithmic expression of the matching law is a biased statistical representation
      of the law itself. In particular, the logarithmic transformation alters the
      quantitative conclusions to be drawn from a least-squares regression analysis. A
      Monte Carlo study of the effect of transforming matching-law data demonstrated
      that (a) the estimates of one or both of the parameters of the generalized
      matching law are biased, (b) the measure of goodness of fit (R(2)) is inaccurate,
      and (c) predictions generated by the fitted parameters are incorrect. Alternative
      approaches to logarithmic transformations are shown to alleviate these problems.

PMID- 16812593
TI  - Temporal reproduction.
AB  - A signal appeared for a certain time period. After the period elapsed, pigeons
      had to begin and complete a sequence of 15 responses in a time window ranging
      from the signal duration to 50% longer. Sessions involved as many as 10 different
      signal durations occurring in a random sequence. The times produced by pigeons
      often were in the same ranges as those that have been found with adult human
      subjects. The average times were described equally well as linear or power
      functions of signal duration. However, instead of the overestimation of durations
      usually found when animals have timed the duration of antecedent stimuli, the
      linear functions suggested that the pigeons underestimated the durations of their
      own behavior. The birds showing the strongest control when the conditions
      involved eight or 10 different duration requirements revealed the constant
      coefficients of variation that support Weber's law and scalar timing theory.
      Scalar timing in temporal differentiation appears to depend on non-ambiguous
      information about the duration required for reinforcement and on a high degree of
      sensitivity to the duration requirement.

PMID- 16812594
TI  - Cognition and behavior analysis.

PMID- 16812595
TI  - Secondary generalization and categorization in pigeons.
AB  - In Experiment 1, one group of pigeons learned to classify a set of stimuli into
      the human language classes cat, flower, car, and chair (categorization); another
      group learned to classify the same set into arbitrary classes
      (pseudocategorization). Then, both groups were trained on a new categorization
      task and their performance compared to that of a control group that had no
      initial classification training. Hull's (1943) notion of secondary generalization
      (generalization that is not based on physical similarity but on mediating
      associations) predicts that categorization experience will facilitate the
      learning of a new categorization task, whereas pseudocategorization experience
      will impair it. However, in Experiment 1, performance on the new categorization
      task was not differently affected by prior experience. In Experiment 2, pigeons
      initially trained to classify a set of 48 stimuli (original training) were later
      trained to classify a subset of four of these stimuli using new responses
      (reassignment training). Then, they were tested on the 44 remaining stimuli.
      Performance better accorded with original than with reassignment training,
      indicating that categorization training did not lead to the formation of
      equivalence classes of stimuli, in which the equivalence relationship is mediated
      by secondary generalization. The lack of evidence of secondary generalization
      implies that our pigeons failed to meet Lea's (1984) criterion for conceptual
      behavior.

PMID- 16812596
TI  - Does conditional discrimination learning by pigeons necessarily involve
      hierarchical relationships?
AB  - Four experiments demonstrate that when putative conditional and discriminative
      cues are presented simultaneously in the single reversal procedure, it is not
      possible to ascribe a uniquely conditional or uniquely discriminative function to
      either of the cues. In Experiment 1, pigeons were trained to respond to a blue
      key and not to a red key while the houselight was on; then in a different session
      they learned the reversal of this discrimination with the houselight off (single
      reversal). Separate groups were tested for color generalization with houselight
      conditions alternating in blocks of trials or for houselight intensity
      generalization with blue and red key colors alternating in blocks of trials. Both
      test procedures revealed a conditional relationship between houselight and key
      color conditions. Experiment 2 produced the same result following training in
      which the key colors were held constant across training sessions while the
      houselight and no houselight conditions varied within sessions. In Experiment 3,
      separate groups were trained with the two procedures but were tested with
      randomly ordered combinations of key colors and houselight intensities. The two
      groups yielded indistinguishable bidimensional generalization gradients with
      peaks at both previously reinforced stimulus combinations. In Experiment 4 the
      subjects were switched from one of these training procedures to the other with no
      decrement in their discriminative performance. We conclude that for successive
      discriminations between conditional- and discriminative-stimulus combinations,
      the notion of a hierarchical relation between conditional and discriminative
      stimuli must be extended to include a symmetrical relationship or the notion
      should be abandoned altogether.

PMID- 16812597
TI  - Functional classes and equivalence relations.
AB  - Three adult subjects were taught a set of two-choice simultaneous
      discriminations, with three positive and three negative stimuli; all possible
      combinations of positive and negative stimuli yielded nine different pairs. The
      discriminations were repeatedly reversed and rereversed, the former positive
      stimuli becoming negative and the former negative stimuli becoming positive. With
      all subjects, a reversal of the contingencies for one pair of stimuli became
      sufficient to change their responses to all of the other pairs. The reversals had
      produced functional stimulus classes. Then, all subjects showed conditional
      discriminations emerging between members of a functional class; given a sample
      from one class and comparisons from both classes, they selected the comparison
      that was in the same class as the sample. Next, 2 of the subjects showed that the
      within-class conditional relations possessed the symmetric and transitive
      properties of equivalence relations; after having been taught to relate new
      stimuli to existing class members, the subjects then matched other class members
      to the new stimuli. Subsequent tests of two-choice discriminations showed that
      the conditional discriminations had transferred functional class membership to
      the new stimuli. The 3rd subject, who did not show equivalence relations among
      functional class members, was also found to have lost the within-class
      conditional relations after the equivalence tests.

PMID- 16812598
TI  - Stimulus equivalence and rule following.
AB  - The present study examined the occurrence of a novel behavior pattern with
      respect to a novel configuration of stimuli enabled by the participation of those
      stimuli in equivalence classes. In Experiment 1, functional substitutabilities
      were established via equivalence between two independent sets of musical stimuli.
      Aspects of stimuli from the two sets were then compounded to produce novel
      stimulus configurations. Behavioral components enabled by each separate class
      combined to produce novel musical performances and accurate descriptions of them.
      In Experiment 2, the impact of experimenter-provided names for equivalence
      classes on the musical performances was investigated in naive subjects by
      establishing similar classes without experimenter-provided names. The results
      indicated few differences in the playing performances under these conditions.
      These experiments demonstrated a possible method for the analysis of rule
      following.

PMID- 16812599
TI  - Use of an ambiguous-sample procedure to establish a cue to forget in pigeons.
AB  - Pigeons were trained on a variation of the matching-to-sample task in which on
      double-sample trials two samples, one associated with each of the comparison
      stimuli, were presented successively. Responding to the comparison associated
      with the first sample was reinforced on half the double-sample trials, and
      responding to the comparison associated with the second sample was reinforced on
      the remaining half. One of two postsample stimuli was presented following the
      termination of each colored sample. A vertical line was presented after a correct
      or target sample, and a horizontal line was presented after an incorrect or
      interfering sample. With extended training, each bird demonstrated above-chance
      accuracy on double-sample trials, providing prima facie evidence that one or both
      of the postsample stimuli exerted control over matching behavior. Experiment 2
      provided evidence that the horizontal line functioned as a cue to forget the code
      activated by the preceding sample stimulus. It was concluded that a condition
      sufficient to establish a postsample stimulus as a cue to forget is that the
      postsample immediately follow presentation of a sample that, if it were to
      control test responding, would lead to nonreinforcement.

PMID- 16812600
TI  - On conditioned reinforcing effects of negative discriminative stimuli.
AB  - Observing responses by pigeons were studied during sessions in which a food key
      and an observing key were available continuously. A variable-interval schedule
      and extinction alternated randomly on the food key. In one condition, food-key
      pecking during extinction decreased reinforcement frequency during the next
      variable-interval component, and in the other condition such pecking did not
      affect reinforcement frequency. Observing responses either changed both keylight
      colors from white to green (S+) or to red (S-) depending on the condition on the
      food key, or the observing responses never produced the S+ but produced the S-
      when extinction was in effect on the food key. Observing responses that produced
      only S- were maintained only when food-key pecking during extinction decreased
      reinforcement frequency in the subsequent variable-interval component. The red
      light conformed to conventional definitions of a negative discriminative
      stimulus, rendering results counter to previous findings that production of S-
      alone does not maintain observing. Rather than offering support for an
      informational account of conditioned reinforcement, the results are discussed in
      terms of a molar analysis to account for how stimuli acquire response-maintaining
      properties.

PMID- 16812601
TI  - Timing multimodal events in pigeons.
AB  - The peak procedure was used in two experiments to study pigeons' ability to time
      multimodal events. In the first experiment, birds were trained to time a single
      event consisting of a 9-s tone or light followed by a 21-s fixed interval
      associated with a signal of light or tone (signal of the other modality). On
      occasional empty trials, different lengths of the first signal were followed by a
      long period of the second signal. Peak response times as a function of the
      duration of the first signal were linear and had a slope of close to one in all
      birds. This indicates that the birds were timing only the second signal. In a
      second experiment, two complex events were used in training. One consisted of a 9
      s tone or light followed by a 21-s fixed interval associated with a light or
      tone. The other consisted of a 21-s tone or light followed by a 9-s fixed
      interval associated with a light or tone. Different durations of the first signal
      were again used on empty trials. Peak response times as a function of the
      duration of the first signal were again linear in all birds. The slope of the
      function was less than one but greater than zero for 3 birds. This indicates that
      these birds were partly timing the entire complex event of 30-s duration and
      partly timing only the second signal of the event. A model is proposed in which
      the bird takes as a criterion for timing a weighted average of different target
      criteria. Comparisons with the performance of rats are made.

PMID- 16812602
TI  - Visually guided catching and tracking skills in pigeons: A preliminary analysis.
AB  - Research on reaching, tracking, and catching in the pigeon has been hampered by
      limitations of technology. A new system was developed in which the target was a
      small rectangle presented on a video display terminal and the pecking response
      was detected with touch technology. The target moved up and down vertically with
      sinusoidal velocity. A coincidence between the location of the pigeon's beak and
      the cursor produced reinforcement. The pigeon pecked ahead and behind the target,
      but most pecks occurred behind the target so the dominant tracking strategy was
      lagging. The pigeon was adept at "catching" the target at many locations
      throughout the trajectory. Transfer of motor learning was tested on probe trials
      during which the trajectory changed from vertical to horizontal. On transfer
      trials the pigeons' dominant pattern of pecking immediately shifted from vertical
      to horizontal. The motor skill displayed by the pigeons was flexible and
      adaptive, suggesting that the pigeons had learned to track the cursor.

PMID- 16812603
TI  - Nonhuman short-term memory: A quantitative reanalysis of selected findings.
AB  - Intense interest in the experimental analysis of nonhuman short-term memory was
      occasioned by the "cognitive revolution" in the early 1970s. As researchers
      tested and refined their theoretical models, a sizable empirical literature on
      the subject rapidly emerged. Generally missing from that literature, however, is
      an integrated account of the empirical laws of delayed stimulus control. In its
      absence, cognitive theories have grown increasingly complex and their connection
      to established principles of learning more remote. The present article reviews a
      representative segment of the nonhuman memory literature in an effort to identify
      and tentatively quantify empirical laws that may underlie some of the major
      findings. Specifically, a delay-reduction principle adapted from the conditioned
      reinforcement literature and a proposed principle of serial stimulus compounds
      were evaluated against data from delayed matching to sample, serial probe
      recognition, differential outcome, directed forgetting, and surprisingness
      preparations. Although by no means offering a complete description of the data,
      the proposed analysis organizes an apparently disparate collection of empirical
      results and suggests several new lines of inquiry into the subject.

PMID- 16812604
TI  - Connectionist models of conditioning: A tutorial.
AB  - Models containing networks of neuron-like units have become increasingly
      prominent in the study of both cognitive psychology and artificial intelligence.
      This article describes the basic features of connectionist models and provides an
      illustrative application to compound-stimulus effects in respondent conditioning.
      Connectionist models designed specifically for operant conditioning are not yet
      widely available, but some current learning algorithms for machine learning
      indicate that such models are feasible. Conversely, designers for machine
      learning appear to have recognized the value of behavioral principles in
      producing adaptive behavior in their creations.

PMID- 16812605
TI  - Determinants of pigeons' waiting time: Effects of interreinforcement interval and
      food delay.
AB  - Four pigeons performed on three types of schedules at short (i.e., 10, 30, or 60
      s) interreinforcement intervals: (a) a delay-dependent schedule where
      interreinforcement interval was held constant (i.e., increases in waiting time
      decreased food delay), (b) an interreinforcement-interval-dependent schedule
      where food delay was held constant (i.e., increases in waiting time increased
      interreinforcement interval), and (c) a both-dependent schedule where increases
      in waiting time produced increases in interreinforcement interval but decreases
      in food delay. Waiting times were typically longer under the delay-dependent
      schedules than under the interreinforcement-interval-dependent schedules. Those
      under both-dependent schedules for 1 subject were intermediate between those
      under the other two schedule types, whereas for the other subjects waiting times
      under the both-dependent procedure were similar either to those under the delay
      dependent schedule or to those under the interreinforcement-interval-dependent
      schedule, depending both on the subject and the interreinforcement interval.
      These results indicate that neither the interreinforcement interval nor food
      delay is the primary variable controlling waiting time, but rather that the two
      interact in a complex manner to determine waiting times.

PMID- 16812606
TI  - Pausing under variable-ratio schedules: Interaction of reinforcer magnitude,
      variable-ratio size, and lowest ratio.
AB  - Pigeons pecked a key under two-component multiple variable-ratio schedules that
      offered 8-s or 2-s access to grain. Postreinforcement pausing and the rates of
      responding following the pause (run rates) in each component were measured as a
      function of variable-ratio size and the size of the lowest ratio in the
      configuration of ratios comprising each schedule. In one group of subjects,
      variable-ratio size was varied while the size of the lowest ratio was held
      constant. In a second group, the size of the lowest ratio was varied while
      variable-ratio size was held constant. For all subjects, the mean duration of
      postreinforcement pausing increased in the 2-s component but not in the 8-s
      component. Postreinforcement pauses increased with increases in variable-ratio
      size (Group 1) and with increases in the lowest ratio (Group 2). In both groups,
      run rates were slightly higher in the 8-s component than in the 2-s component.
      Run rates decreased slightly as variable-ratio size increased, but were
      unaffected by increases in the size of the lowest ratio. These results suggest
      that variable-ratio size, the size of the lowest ratio, and reinforcer magnitude
      interact to determine the duration of postreinforcement pauses.

PMID- 16812607
TI  - Humans' sensitivity to variation in reinforcer amount: Effects of the method of
      reinforcer delivery.
AB  - Two experiments examined human subjects' sensitivity to variation in reinforcer
      amount under different methods of reinforcer delivery. Subjects chose between
      schedules varying in terms of amount and/or delay of reinforcement, the
      reinforcer being points exchangeable for money. In Experiment 1, reinforcer
      amount was manipulated by varying the monetary value of the points across
      conditions while the number of seconds of access to a consummatory response
      remained constant. Choice was strongly sensitive to reinforcer amount and
      indicative of self-control, as in previous experiments. In Experiment 2,
      reinforcer amount was manipulated by automatically delivering different numbers
      of points during the amount period, and the consummatory response was eliminated.
      Sensitivity to variation in reinforcer amount was significantly lower than in
      Experiment 1. Furthermore, the subjects in Experiment 2 exhibited significantly
      less self-control than did the subjects in Experiment 1. Humans' sensitivity to
      variation in reinforcer amount appears to be affected by factors that enhance the
      discrimi-nability of the consequences of responding.

PMID- 16812608
TI  - Serial conditioning as a function of stimulus, response, and temporal
      dependencies.
AB  - Six experiments were used to examine the effects of explicit response, stimulus,
      and temporal dependencies on responding in an interfood interval. The first two
      experiments demonstrated that 10-segment 60-s interfood clocks controlled similar
      distributions of key pecking in pigeons regardless of whether response
      reinforcement contiguity was required, allowed, or precluded. The third and
      fourth experiments found that in the absence of an explicit response
      reinforcement dependency, systematic explicit stimuli in an interfood interval
      were sufficient to establish and maintain the characteristic distribution of key
      pecking and that an interval without an explicit clock failed to establish or
      maintain key pecking. The last two experiments demonstrated that the interfood
      interval need not be of fixed length, and that a simple correlation of stimuli
      with increments from either a minimum to a maximum imminency or probability of
      food presentation controlled behavior in a similar manner. Successively higher
      rates generally occurred to successively later stimuli in the upper half of the
      range.

PMID- 16812609
TI  - Delay and number of food reinforcers: Effects on choice and latencies.
AB  - Pigeons were given a choice between two identical-duration situations (terminal
      links of chain schedules). One terminal link of the choice pair provided two food
      deliveries, and the other provided five. The exact times of these food deliveries
      differed between the terminal links and were varied over conditions. A single
      response during the initial link gave immediate access to the corresponding
      terminal link. Forced trials, during which only one of the initial-link keys was
      lighted, were interspersed with choice trials during which both initial-link keys
      were lighted. Choice tended to favor whichever terminal link was correlated with
      the higher sum of the immediacies (i.e., the sum of the reciprocals of the delays
      to each of the reinforcers following the choice, with all delays measured from
      the choice). Latencies on forced trials and on choice trials also were related
      (negatively) to the sum of the immediacies. This correlation among response
      measures (choice and latencies) suggests that both measures are manifestations of
      the effect of conditioned reinforcement on response tendencies.

PMID- 16812610
TI  - Income maximizing on concurrent ratio-interval schedules of reinforcement.
AB  - Three experiments examined the effect of food availability on pigeons' choice
      behavior under concurrent schedules of reinforcement. In Experiment 1, 3 pigeons
      earned their daily food ration by choosing, in 30-min sessions, between
      concurrent variable-ratio 30 variable-interval 40-s schedules. Food presentations
      during both schedules lasted 2 or 12 s, depending upon the condition. Relative
      variable-ratio response rate was inversely related to hopper duration. In
      Experiment 2, 4 pigeons received their daily feeding by responding on the same
      schedule pair as in Experiment 1 (with 4-s food presentations) in sessions that
      varied in length from 10 to 30 min, depending on the condition. The length of a
      vertical slit projected on a response key increased with time so that "passage of
      time" might be more easily discriminable. As session duration decreased, relative
      variable-ratio response rate increased. In Experiment 3, 4 pigeons chose between
      two variable-interval 40-s schedules. One schedule operated without regard to the
      schedule selected, whereas the other operated only when the subject responded in
      its presence (dependent). Although these schedules had the same feedback
      function, preference for the dependent variable interval increased as session
      duration decreased from 30 to 10 min. The preference changes in these studies
      reveal the operation of an income-maximizing process in choice.

PMID- 16812611
TI  - Verbal self-reports of delayed matching to sample by humans.
AB  - Undergraduates participated in two experiments to develop methods for the
      experimental analysis of self-reports about behavior. The target behavior was the
      choice response in a delayed-matching-to-sample task in which monetary
      reinforcement was contingent upon both speed and accuracy of the choice. In
      Experiment 1, the temporal portion of the contingency was manipulated within each
      session, and the presence and absence of feedback about reinforcement was
      manipulated across sessions. As the time limits became stricter, target response
      speeds increased, but accuracy and reinforcement rates decreased. When feedback
      was withheld, further reductions in speed and reinforcement occurred, but only at
      the strictest time limit. Thus, the procedures were successful in producing
      systematic variation in the speed, accuracy, and reinforcement of the target
      behavior. Experiment 2 was designed to assess the influence of these
      characteristics on self-reports. In self-report conditions, each target response
      was followed by a computer-generated query: "Did you earn points?" The subject
      reported by pressing "Yes" or "No" buttons, with the sole consequence of
      advancing the session. In some cases, feedback about reinforcement of the target
      response followed the reports; in other cases it was withheld. Self-reports were
      less accurate when the target responses occurred under greater time pressure.
      When feedback was withheld, the speed of the target response influenced reports,
      in that the probability of a "Yes" report increased directly with the speed of
      accurate target responses. In addition, imposing the self-report procedure
      disrupted target performance by reducing response speeds at the strictest time
      limit. These results allow investigation of issues in both behavioral and
      cognitive psychology. More important, the overall order in the data suggests
      promise for the experimental analysis of self-reports by human subjects.

PMID- 16812612
TI  - Free birds aren't fat: Weight gain in captured wild pigeons maintained under
      laboratory conditions.
AB  - Nine feral pigeons, 5 from an urban setting and 4 from a rural setting, were
      captured and maintained for 42 days under free-feeding conditions comparable to
      those arranged for laboratory subjects. On average, birds increased their body
      weights by 17% over this period. The range of increase across birds was 9 to 30%.
      These findings suggest that the food deprivation arranged for laboratory pigeons,
      which is characteristically 80% of free-feeding weights, may in some sense be
      less severe than it first appears.

PMID- 16812613
TI  - Variable-interval schedule performance in open and closed economies.
AB  - In two experiments, pigeons obtained food according to variable-interval
      schedules. In the first experiment, equivalent variable-interval schedules with
      average interreinforcer intervals ranging between 10 and 80 s in different
      conditions were studied in both open and closed economies. Response rates
      increased as reinforcement frequency decreased in the closed economy. By
      contrast, in the open economy response rates decreased for 1 bird and were
      variable for the other as reinforcement frequency decreased. The second
      experiment showed that the differences in the functions between responding and
      reinforcement frequency in the two types of economies were not due to changes in
      deprivation level. These results suggest that open and closed economies yield
      different behavioral effects. This conclusion is supported further by a
      reconsideration of previous findings that appear counter to the conclusion.

PMID- 16812614
TI  - Delayed and current stimulus control in successive discriminations.
AB  - In a successive discrimination in which successively alternating red and green
      hues signaled component variable-interval schedules, sensitivity of the ratio of
      responses in the two components to variation in the component reinforcer ratio
      decreased systematically during the course of the component. This decrease in
      stimulus control or discrimination over the course of the component was shown to
      be the result of delayed control of responding during the component by the
      stimulus transition between components. When the red-green stimulus transition
      was altered by interpolating a white stimulus at the end of each 60-s component,
      discrimination at the beginning of the component (measured by the power-function
      exponent for sensitivity to reinforcement) was reduced. Conditions with the white
      stimulus inserted in other quarters of the component indicated that the current
      discriminative stimulus exerts control over responding throughout the component,
      whereas during about the first half of the component, response differentials are
      influenced by the transition between discriminative stimuli.

PMID- 16812616
TI  - The k & s in Brazil.

PMID- 16812615
TI  - Academic roots: Columbia University, 1943-1951.

PMID- 16812617
TI  - Category discrimination by pigeons using five polymorphous features.
AB  - Eight pigeons were trained to discriminate between sets of color photographs of
      natural scenes. The scenes differed along five two-valued dimensions (site,
      weather, camera distance, camera orientation, and camera height), and all
      combinations of the feature values were used. One value of each dimension was
      designated as positive, and slides containing three or more positive feature
      values were members of the positive stimulus set. Thus, each feature had an
      equal, low, correlation with reinforcement, and all features had zero
      correlations with each other. Seven of the 8 pigeons learned this discrimination,
      and their responding came under the control of all five features. Within the
      positive and negative stimulus sets, response rates were higher to stimuli that
      contained more positive feature values. Once discrimination had been achieved,
      reversal training was given using a subset of the slides. In this subset, only a
      single feature was correlated with reinforcement. All pigeons learned this
      reversal successfully and generalized it to additional photographs with the same
      feature content. After reversal, the original reinforcement contingencies were
      reinstated, and training was continued using all the slides except those that had
      been used in reversal. Reversal generalized to these slides to some extent.
      Analysis of the response rates to individual slides showed that, compared with
      prereversal training, only the feature that had been subjected to reversal
      contingencies showed a reversed correlation with response rate. The remaining
      features showed the same correlation with response rate as they had before
      reversal training. Thus, reversal on some members of a category following
      category discrimination training led to generalization to stimuli within the
      category that were not involved in the reversal, but not to features that were
      not reversed. It is therefore inappropriate to refer to the pigeons as learning a
      concept.

PMID- 16812618
TI  - Additional-delay schedules: A continuum of temporal contingencies by varying food
      delay.
AB  - Pigeons performed on discrete-trial, temporally defined schedules in which the
      food delay (D) was adjusted according to the latency of the key peck (X) and two
      schedule parameters (t and A). The schedule function was D = A(t - X), where D is
      the experienced delay between a response and a reinforcer. The schedule parameter
      t is the maximum value below which the present contingencies occur. A is the
      additional delay to reinforcement for each second the response latency is shorter
      than the t value. When A = 0 s, the schedule is a continuous reinforcement
      schedule with immediate reinforcement. When A = 1 s, the schedule is a
      conjunctive fixed-ratio 1 fixed-time t-s schedule. When A approaches infinity,
      the schedule becomes a differential reinforcement of long latency schedule. The
      latencies for subjects with t = 10 s and t = 30 s were observed with the present
      schedules having seven values for A between 0 s and 11 s. In addition, the
      latencies for subjects for which t = 30 s were observed at an A value of 31 s to
      41 s. As the A value increased, the latencies approached the t value for subjects
      for which t = 10 s. The latencies for 30-s-t subjects did not approach t, even
      when the A value was 41 s. The latencies for 10-s-t subjects at 11-s A value were
      longer than those under yoked conditions having exactly the same
      delays/interreinforcement intervals. These results demonstrated a continuum of
      latency related to the schedule continuum (value of A) at a small t value.

PMID- 16812620
TI  - The experimental analysis of human behavior (Editorial).

PMID- 16812619
TI  - The establishment of stimulus control by instructions and by differential
      reinforcement.
AB  - A repeated acquisition design was used to study the effects of instructions and
      differential reinforcement on the performance of complex chains by
      undergraduates. The chains required responding on a series of keys that
      corresponded to characters that appeared on a monitor. Each day, subjects
      performed a new chain in a learning session and later relearned the same chain in
      a test session. Experiment 1 replicated previous research by showing that
      instructional stimuli paired with the correct responses in the learning sessions,
      combined with differential reinforcement in both learning and test sessions,
      resulted in stimulus control by the characters in each link. Experiment 2
      separated the effects of instructional stimuli and differential reinforcement,
      and showed that stimulus control by the characters could be established solely by
      differential reinforcement during the test sessions. Experiment 3 showed that
      when a rule specified the relation between learning and test sessions, some
      subjects performed accurately in the test sessions without exposure to any
      differential consequences. This rule apparently altered the stimulus control
      properties of the characters much as did differential reinforcement during
      testing. However, compared to differential reinforcement, the rule established
      stimulus control more quickly.

PMID- 16812621
TI  - The momentum of human behavior in a natural setting.
AB  - Adults with mental retardation in a group home received popcorn or coffee
      reinforcers for sorting plastic dinnerware. In Part 1 of the experiment,
      reinforcers were dispensed according to a variable-interval 60-s schedule for
      sorting dinnerware of one color and according to a variable-interval 240-s
      schedule for sorting dinnerware of a different color in successive components of
      a multiple schedule. Sorting rates were similar in baseline, but when a video
      program was shown concurrently, sorting of dinnerware was more resistant to
      distraction when correlated with a higher rate of reinforcement. In Part 2 of the
      experiment, popcorn or coffee reinforcers were contingent upon sorting both
      colors of dinnerware according to variable-interval 60-s schedules, but
      additional reinforcers were given independently of sorting according to a
      variable-time 30-s schedule during one dinnerware-color component. Baseline
      sorting rate was lower but resistance to distraction by the video program was
      greater in the component with additional variable-time reinforcers. These results
      demonstrate that resistance to distraction depends on the rate of reinforcers
      obtained in the presence of component stimuli but is independent of baseline
      response rates and response-reinforcer contingencies. Moreover, these results are
      similar to those obtained in laboratory studies with pigeons, demonstrating that
      the determination of resistance to change by stimulus-reinforcer relations is not
      confined to controlled laboratory settings or unique to the pigeon.

PMID- 16812622
TI  - Relations between baseline contingencies and equivalence probe performances.
AB  - Following the emergence of two three-member equivalence classes (A1B1C1 and
      A2B2C2), 5 college students were exposed to one or more changes in the
      reinforcement contingencies controlling baseline conditional discriminations. AC
      relations were either reversed (i.e., C2 was reinforced and C1 punished when A1
      was the sample; C1 was reinforced and C2 punished when A2 was the sample) or
      arranged randomly (i.e., C2 and C1 were reinforced and punished equally often in
      the presence of A1 and A2). In a third condition, the original AB and AC
      relations were reversed. Results showed that although baseline conditional
      discrimination performances were under the control of reinforcement
      contingencies, and performances on symmetry trials varied with baseline
      responding for 3 of 4 subjects when contingencies were reversed, performances on
      transitivity probes remained consistent with the initial equivalence class. These
      inconsistencies between probe and baseline performances were striking because
      conditional discriminations are thought to be the determinants of equivalence
      class performance. Similarly, the contrast between performances on symmetry and
      transitivity probes was of theoretical interest because equivalence classes are
      defined by congruent patterns of responding on probe trials.

PMID- 16812623
TI  - Effects of response variability on the sensitivity of rule-governed behavior.
AB  - Two experiments examined the relation between response variability and
      sensitivity to changes in reinforcement contingencies. In Experiment 1, two
      groups of college students were provided complete instructions regarding a button
      pressing task; the instructions stated "press the button 40 times for each point"
      (exchangeable for money). Two additional groups received incomplete instructions
      that omitted the pattern of responding required for reinforcement under the same
      schedule. Sensitivity was tested in one completely instructed and one
      incompletely instructed group after responding had met a stability criterion, and
      for the remaining two groups after a short exposure to the original schedule. The
      three groups of subjects whose responding was completely instructed or who had
      met the stability criterion showed little variability at the moment of change in
      the reinforcement schedule. The responding of these three groups also was
      insensitive to the contingency change. Incompletely instructed short-exposure
      responding was more variable at the moment of schedule change and was sensitive
      to the new contingency in four of six cases. In Experiment 2, completely and
      incompletely instructed responding first met a stability criterion. This was
      followed by a test that showed no sensitivity to a contingency change. A
      strategic instruction was then presented that stated variable responding would
      work best. Five of 6 subjects showed increased variability after this
      instruction, and all 6 showed sensitivity to contingency change. The findings are
      discussed from a selectionist perspective that describes response acquisition as
      a process of variation, selection, and maintenance. From this perspective,
      sensitivity to contingency changes is described as a function of variables that
      produce response variability.

PMID- 16812624
TI  - Performance of children under a multiple random-ratio random-interval schedule of
      reinforcement.
AB  - Three children, aged 1.5, 2.5, and 4.5 years, pressed telegraph keys under a two
      component multiple random-ratio random-interval schedule of reinforcement. In the
      first condition, responses on the left key were reinforced under a random
      interval schedule and responses on the right key were reinforced under a random
      ratio schedule. In the second condition, the schedule components were reversed.
      In the third condition, the original arrangement was reinstated. For all
      subjects, rates of responding were higher in the random-ratio component despite
      higher rates of reinforcement in the random-interval component. The average
      interreinforcement interval of the random-interval component was increased in the
      fourth condition, resulting in more similar rates of reinforcement for both
      schedule components, and then returned to its original value in the fifth
      condition. In both conditions, all subjects continued to exhibit higher rates of
      responding in the ratio component than in the interval component. Although these
      observations are consistent with results from studies with pigeons, it is argued
      that the response-rate differences between the interval and ratio schedule
      components are sufficient to demonstrate schedule sensitivity.

PMID- 16812625
TI  - The effects of verbal performance descriptions on nonverbal operant responding.
AB  - The effect of reinforced verbal descriptions on key-pressing rate was studied in
      the context of reinforcement for pressing on schedules opposed to the verbal
      description and schedules delivering a constant or randomly chosen point value
      regardless of pressing rate (nondifferential schedules). Undergraduates' key
      presses produced points exchangeable for lottery tickets on alternating
      schedules. Subjects experienced one of four manipulations. In Experiment 1, after
      schedule control had been demonstrated using a "medium rate" schedule for each of
      two response keys, subjects were awarded maximum points for choosing one of five
      verbal descriptions of "the best way to earn points" for each key. Subjects
      experienced either (a) maximum points for verbal descriptions of "press very
      fast" for one key and "press very slowly" for the other, with the schedule
      gradually moved from medium to oppose this description, or (b) maximum schedule
      points for a very fast rate on one key and very slow rate on the other, with the
      maximum points for verbal descriptions gradually moved to oppose the schedule.
      Key-pressing rates conformed to the active schedule, not to the verbal
      performance description. In Experiment 2 subjects received maximum points for
      verbal descriptions of "press very fast" for one key and "press very slowly" for
      the other while the same nondifferential schedule was operative for both keys.
      Correspondence of pressing rate to verbal description was either complete,
      transient, or absent. The precise discriminative control of the schedules
      employed may account for less verbal response-rate control in the present versus
      past research. Possible differences between computer- and experimenter-generated
      verbal behavior are discussed.

PMID- 16812626
TI  - Three-term contingency patterns in mother-child verbal interactions during first
      language acquisition.
AB  - Selections from a large longitudinal data set of verbal interactions between a
      mother and her child are presented. Two sets of three-term contingency sequences
      that seemed to reflect maternal rewards and corrections were noted. Both the
      antecedents as well as the immediate consequences of maternal interventions are
      presented to explore training and learning processes. The observed frequencies of
      three-step sequences are compared to those expected based upon Markov-chain logic
      to substantiate the patterning of the interactions. Behavioral conceptualizations
      of the learning process are supported by these analyses, although their
      sufficiency is questioned. It is suggested that maternal rewards and corrections
      should be integrated with perceptual, cognitive, and social learning
      conceptualizations in a skill-learning approach to explain the complexity of
      language transmission and acquisition processes.

PMID- 16812627
TI  - B. F. Skinner-the last few days.

PMID- 16812628
TI  - Multiple determinants of the effects of reinforcement magnitude on free-operant
      response rates.
AB  - Four experiments examined the effects of increasing the number of food pellets
      given to hungry rats for a lever-press response. On a simple variable-interval 60
      s schedule, increased number of pellets depressed response rates (Experiment 1).
      In Experiment 2, the decrease in response rate as a function of increased
      reinforcement magnitude was demonstrated on a variable-interval 30-s schedule,
      but enhanced rates of response were obtained with the same increase in
      reinforcement magnitude on a variable-ratio 30 schedule. In Experiment 3, higher
      rates of responding were maintained by the component of a concurrent variable
      interval 60-s variable-interval 60-s schedule associated with a higher
      reinforcement magnitude. In Experiment 4, higher rates of response were produced
      in the component of a multiple variable-interval 60-s variable-interval 60-s
      schedule associated with the higher reinforcement magnitude. It is suggested that
      on simple schedules greater reinforcer magnitudes shape the reinforced pattern of
      responding more effectively than do smaller reinforcement magnitudes. This effect
      is, however, overridden by another process, such a contrast, when two magnitudes
      are presented within a single session on two-component schedules.

PMID- 16812629
TI  - Quantitative and methodological aspects of stimulus equivalence.
AB  - The number of different ways of linking stimuli in the training phase of a
      conditional discrimination procedure designed to teach equivalence relations has
      hitherto been underestimated. An algorithm from graph theory that produces the
      correct number of such different ways is given. The establishment of equivalence
      relations requires transitive stimulus control. A misconception in a previous
      analysis of the conditions necessary for demonstrating transitive stimulus
      control is indicated. This misconception concerns responding in an unreinforced
      test trial to a negative rather than a positive comparison stimulus. Such
      behavior cannot be attributed to discriminative control by degree of association
      with reinforcement if the negative comparison stimulus has been less associated
      with reinforcement than the positive comparison stimulus in an antecedent
      training phase.

PMID- 16812630
TI  - Choice, changeover, and travel: A quantitative model.
AB  - Six pigeons were trained on concurrent variable-interval schedules in which
      responding on fixed-interval schedules was required to give access to the
      alternate schedule. Responding on the concurrent schedules was not allowed, after
      changing over had commenced, until the changeover schedule had been completed. In
      Parts 1 to 3 of the experiment, the changeover fixed-interval schedules were
      equal and were 0 s, 10 s, and 20 s, respectively. In each part, the relative
      frequency of reinforcement obtained on the concurrent schedules was varied over
      at least five conditions. In Part 4, the concurrent schedules were equal, and one
      changeover fixed-interval schedule was twice the other. Under these conditions,
      the absolute sizes of the changeover schedules were varied. Increasing the
      changeover requirement from 0 s to 10 s (Parts 1 and 2) resulted in increases in
      the sensitivity of behavior allocation to reinforcers obtained, but no further
      increase was obtained when the changeover schedules were increased to 20 s (Part
      3). In Part 4, performance was biased towards the concurrent schedule that took
      less time to enter. These results are consistent with a subtractive punishment
      model of travel in which the degree of punishment is measured by the number of
      reinforcers apparently lost from a schedule when the subject changes to that
      schedule. Absolute times spent on the main keys could be accurately described by
      a previous model of changeover performance.

PMID- 16812631
TI  - Irrelevance of sample stimuli and directed forgetting in pigeons.
AB  - A successive matching procedure was used to investigate which aspect of the test
      omission procedure is responsible for establishing a postsample stimulus as a cue
      to forget in pigeons. It was found that a postsample stimulus that reliably
      followed a sample that was irrelevant to performance functioned as a cue to
      forget. This result was obtained regardless of whether termination of that
      postsample stimulus was followed by reinforcement or by the presentation of
      sample-independent discriminative stimuli. It was also found that a postsample
      stimulus that functioned as a cue to forget at the beginning of training lost
      that function when it was repeatedly presented on trials in which the sample was
      relevant to performance. These findings reveal that (a) neither a reduction in
      reinforcement rate nor the omission of the opportunity for discriminated
      responding is necessary to establish an effective cue to forget and (b)
      irrelevance of the sample to performance is a sufficient condition to establish a
      cue to forget. These results suggest that a postsample stimulus that is presented
      on trials in which remembering the sample is not reinforced differentially will
      come to set the occasion for not remembering the sample.

PMID- 16812632
TI  - Concurrent schedules: Effects of time- and response-allocation constraints.
AB  - Five pigeons were trained on concurrent variable-interval schedules arranged on
      two keys. In Part 1 of the experiment, the subjects responded under no
      constraints, and the ratios of reinforcers obtainable were varied over five
      levels. In Part 2, the conditions of the experiment were changed such that the
      time spent responding on the left key before a subsequent changeover to the right
      key determined the minimum time that must be spent responding on the right key
      before a changeover to the left key could occur. When the left key provided a
      higher reinforcer rate than the right key, this procedure ensured that the time
      allocated to the two keys was approximately equal. The data showed that such a
      time-allocation constraint only marginally constrained response allocation. In
      Part 3, the numbers of responses emitted on the left key before a changeover to
      the right key determined the minimum number of responses that had to be emitted
      on the right key before a changeover to the left key could occur. This response
      constraint completely constrained time allocation. These data are consistent with
      the view that response allocation is a fundamental process (and time allocation a
      derivative process), or that response and time allocation are independently
      controlled, in concurrent-schedule performance.

PMID- 16812633
TI  - Discrimination training facilitates pigeons' performance on one-trial-per-day
      delayed matching of key location.
AB  - Six pigeons were tested on a one-trial-per-day variant of delayed matching of key
      location. In one condition, a trial began with the illumination of a pair of
      quasi-randomly selected pecking keys in a large 10-key test box. Pigeons' pecks
      to one key (the sample) were reinforced with 8-second access to grain on a
      variable-interval 30-second schedule, whereas pecks to the other key (the
      distractor) had no scheduled consequences. In the second condition, the
      nonreinforced distractor was not presented. In both conditions, subjects were
      removed from the apparatus after 15 minutes and placed in a holding cage.
      Subjects were subsequently replaced in the box after a delay (retention interval)
      of 30 seconds and were reexposed to the illuminated sample and distractor keys
      for 1 minute. If a pigeon made more pecks to the sample during this interval, the
      distractor was extinguished and subsequent pecks to the sample were reinforced on
      the previous schedule for an additional 15 minutes. If, however, a pigeon made
      more pecks to the distractor, both keys were extinguished and the subject was
      returned to its home cage. For all subjects, matching-to-sample accuracy was
      higher in the first condition. In a second experiment, the retention interval was
      increased to 5, 15, and 30 minutes, and then to 1, 2, 4, 8, 12, and 24 hours.
      Most subjects remembered the correct key location for up to 4 hours, and in one
      case, up to 24 hours, demonstrating a spatial-memory proficiency far better than
      previously reported in this species on delayed matching tasks. The results are
      discussed in terms of the commonly held distinction between working and reference
      memory.

PMID- 16812634
TI  - Effects of reinforcing preselected approximations on the topography of the rat's
      bar press.
AB  - The effects of different shaping approximations on the topography of the rat's
      bar press were investigated in two experiments. Behavior was classified into
      discrete components, and changes in components and their sequential organization
      were analyzed. Experiment 1 examined response form early in training and found
      that specific components reinforced during shaping were incorporated into press
      sequences. Experiment 2 investigated how response form changed when a shaping
      contingency was relaxed later in training. Two topographies were selected for
      reinforcement, and both appeared in the press sequences of all subjects by the
      end of shaping. Subsequently, all variations of bar pressing were reinforced, and
      neither topography was necessary to satisfy the contingency. Although the
      frequency of the topographies reinforced during shaping declined for 3 of 4
      subjects during this phase, the most frequent press sequence for 2 rats at the
      end of training included both unnecessary topographies. Variability in press
      topographies declined when all emitted variants were reinforced. However, all
      subjects emitted novel response forms throughout training. The results
      demonstrate that specific response-reinforcer contingencies influence response
      form by modulating component availability and organization.

PMID- 16812635
TI  - Choice by rats for enriched versus standard home cages: Plastic pipes, wood
      platforms, wood chips, and paper towels as enrichment items.
AB  - The purpose of the present study was to determine whether simple additions to the
      home cages of rats made those cages preferable to standard housing arrangements.
      Results indicated that most rats preferred cages with wood platforms, wood chips,
      and paper towels to otherwise identical cages without these items. Wood chips
      were not, however, practical with the cages used in the present study. Plastic
      pipes caused no problems but were not preferred by most animals. Both wood
      platforms and paper towels created no problems and appeared to be useful as
      enrichment items. The latter were preferred to the former in a direct comparison.

PMID- 16812636
TI  - Context specificity of operant discrimination performance in pigeons.
AB  - In an experiment designed to investigate odors as potential retrieval cues in
      pigeons' memory (i.e., as conditional stimuli), 8 pigeons first learned to peck a
      red keylight (S+, reinforced) and not a blue one (S-, extinguished) in the
      presence of either a eucalyptus oil or isoamyl acetate odor. They were repeatedly
      switched between two chambers with the same odor to habituate any reaction to the
      switching that would be required for eventual testing for conditional control by
      the odors. Next, the birds learned the reversal (blue S+, red S-) in the presence
      of the alternative odor in one of these chambers. When the birds were then
      switched to the alternative chamber for additional training, although the odor
      was still appropriate to the reversal problem, behavior appropriate to the
      original training condition recurred. Testing indicated that reversal performance
      was specific to the one chamber in which it had been trained.

PMID- 16812637
TI  - Stimulus control of Pavlovian facilitation.
AB  - Two experiments were conducted using an autoshaping procedure with pigeons to
      examine whether dimensional stimulus control by a Pavlovian facilitator parallels
      the control established following operant discrimination training. Facilitation
      training consisted of the presentation of a black vertical line on a white
      background as the B stimulus in a feature-positive discrimination in which the A
      stimulus (white keylight) was followed by grain presentation only if preceded by
      B. In this way, B facilitates or sets the occasion for pecking at A. Subsequent
      testing for generalization along the line-orientation dimension produced
      decremental gradients when the facilitation paradigm incorporated an explicit
      feature-negative stimulus (B-). These results parallel the decremental control
      obtained following operant discrimination training and suggest that Pavlovian
      facilitators and instrumental discriminative stimuli are functionally equivalent.

PMID- 16812638
TI  - Violations of stochastic transitivity on concurrent chains: Implications for
      theories of choice.
AB  - The concurrent-chains procedure has been used to measure how choice depends on
      various aspects of reinforcement, such as its delay and its magnitude. Navarick
      and Fantino (1972, 1974, 1975) have found that choice in this procedure can
      violate the condition of stochastic transitivity that is required if a
      unidimensional scale for reinforcements is to be possible. It is shown in this
      paper that two simple unidimensional models of choice on concurrent chains can
      produce violations of stochastic transitivity. It is argued that such violations
      may result from the complex contingencies of the concurrent-chains procedure.

PMID- 16812639
TI  - Behavior-dependent reinforcer-rate changes in concurrent schedules: A further
      analysis.
AB  - Six pigeons were trained on concurrent variable-interval schedules in three
      different procedures. The first procedure was a standard concurrent schedule, and
      the relative reinforcer frequency for responding was varied. The second was a
      schedule in which a relative left-key response rate (over a fixed period of time)
      exceeding .75 produced, in the next identical time period a higher reinforcer
      rate on the right key. If this criterion was not exceeded, equal reinforcer rates
      were arranged on the two keys in this period. This was the dependent procedure.
      In the third (independent) procedure, the periods of higher right-key reinforcer
      rates occurred with the same probability as in the second procedure, but occurred
      independently of behavior. In the second and third procedures, the fixed-time
      period (window) was varied from 5 s to 60 s, and to 240 s in the second procedure
      only. Performance on the two keys was similar in the concurrent and independent
      procedures. The procedure used in the dependent conditions generally affected
      performance when the windows were shorter than about 30 s. Models of performance
      that assume that subjects do not discriminate changes in local relative
      reinforcer rates cannot account for the data. Moreover, existing models are
      inherently unable to account for the effects of contingencies of reinforcement
      between responding on one alternative and gaining reinforcers on another that are
      arranged or that emerge as a result of time allocated to alternative schedules.
      Undermatching on concurrent variable-interval schedules may result from such
      emergent contingencies.

PMID- 16812640
TI  - Superior-subordinate dyads: Dependence of leader effectiveness on mutual
      reinforcement contingencies.
AB  - Task contingencies were modeled from bureaucratic organizations in which vague
      job descriptions provide incomplete contingency specifications. Response rates
      within dyads were examined using two nonsocial, two social, and two control
      contingencies. In the first social contingency, responses by the superior
      produced monetary reinforcement for a subordinate while the superior received no
      reinforcement from his subordinate. A second social contingency was identical to
      the first except that the subordinate's rate of responding determined the rate of
      reinforcement delivered to his superior. Within this contingency, mutual
      reinforcement occurred whenever rates of superior and subordinate responding were
      correlated. Two control contingencies were identical to the second social
      contingency except that either the superior or the subordinate received a rate of
      response-independent reinforcement virtually identical to the rate received
      during the second social contingency. Leadership, in this context, was the
      difference between rates of subordinate responding produced by a nonsocial
      contingency and rates produced by each of the two social contingencies. The two
      nonsocial contingencies supported almost no responding among subjects. The first
      social contingency produced minimal levels of leadership within every dyad. The
      second social contingency produced high levels of leadership. Response
      independent reinforcement generally reduced or eliminated responding.

PMID- 16812641
TI  - The transfer of specific and general consequential functions through simple and
      conditional equivalence relations.
AB  - The purpose of this study was to examine the transfer of consequential
      (reinforcement and punishment) functions through equivalence relations. In
      Experiment 1, 9 subjects acquired three three-member equivalence classes through
      matching-to-sample training using arbitrary visual forms. Comparison stimuli were
      then given conditioned reinforcement or punishment functions by pairing them with
      verbal feedback during a sorting task. For 8 of the 9 subjects, trained
      consequential functions transferred through their respective equivalence classes
      without additional training. In Experiment 2, transfer of function was initially
      tested before equivalence testing per se. Three of 4 subjects showed the transfer
      without a formal equivalence test. In Experiment 3, 3 subjects were given
      training that gave rise to six new three-member conditional equivalence classes.
      For 2 of the subjects, the same stimulus could have either a reinforcement or
      punishment function on the basis of contextual cues that defined its class
      membership. Experiment 4 assessed whether equivalence training had established
      general or specific consequential functions primarily by adding novel stimuli in
      the transfer test. Subjects treated even novel feedback stimuli in the transfer
      test as consequences, but the direction of consequential effects depended upon
      the transfer of specific consequential functions through equivalence relations.

PMID- 16812642
TI  - Local contrast in behavior allocation during multiple-schedule components.
AB  - Allocation of responses between two keys was studied during two alternating
      multiple-schedule components. Responses were recorded in successive quarters of
      each component. Variable-interval reinforcer schedules on the two keys were
      constant throughout the experiment for one (constant) component and were varied
      over conditions on one key for the other, producing changes in reinforcer ratios
      for the varied component. Behavior allocation for the first quarter of the
      constant component was inversely related to varied-component reinforcer ratios, a
      form of local contrast, but this relationship was not observed later in the
      component. During the first quarter of the varied component, slopes of matching
      lines were high and decreased later in the component. It is argued that this form
      of local contrast cannot be explained in terms of reallocation of extraneous
      reinforcers between components, and that the matching law for concurrent operants
      does not capture some sources of control over behavior allocation. A simple
      extension of the matching law is offered that adequately describes behavior
      changes during both components. A version of this formulation can predict
      contrast effects in absolute response rates.

PMID- 16812643
TI  - The future of behavior analysis (Editorial).

PMID- 16812644
TI  - Contingent reviews (Editorial).

PMID- 16812645
TI  - On being narrowly broad (Editorial).

PMID- 16812646
TI  - Effects of reinforcer delays on choice as a function of income level.
AB  - Three rats earned their daily food ration by responding during individual trials
      either on a lever that delivered one food pellet immediately or on a second lever
      that delivered three pellets after a delay that was continuously adjusted to
      ensure substantial responding to both alternatives. Choice of the delayed
      reinforcer increased when the number of trials per session was reduced. This
      result suggests that models seeking closure on choice effects must include a
      parameter reflecting how preference changes with sessionwide income. Moreover,
      models positing that reinforcer probability and immediacy (1/delay) function
      equivalently in choice are called into question by the finding that probability
      and immediacy produce opposing effects when income level is changed.

PMID- 16812647
TI  - Fixed-ratio pausing: Joint effects of past reinforcer magnitude and stimuli
      correlated with upcoming magnitude.
AB  - Pigeons responded on fixed-ratio schedules ending in small or large reinforcers
      (grain presentations of different duration) interspersed within each session. In
      mixed-schedule conditions, the response key was lit with a single color
      throughout the session, and pausing was directly related to the past reinforcer
      (longer pauses after large reinforcers than after small ones). In multiple
      schedule conditions, different colors accompanied the ratios ending in small and
      large reinforcers, and pausing was affected by the upcoming reinforcer as well as
      the past one. Pauses were shorter before large reinforcers than before small
      ones, but they continued to be longer after large reinforcers than after small
      ones. The influence of the past reinforcer was modulated by the magnitude of the
      upcoming reinforcer; in the presence of the stimulus before the small reinforcer,
      the effect of the past reinforcer was enhanced relative to its effect in the
      stimulus before the large reinforcer. These results show that pausing between
      ratios is jointly determined by two competing factors: past conditions of
      reinforcement and stimuli correlated with upcoming conditions.

PMID- 16812648
TI  - Effects of stimulus frequency and reinforcement variables on reaction time.
AB  - Pigeons pecked at one of two black forms, "+" or "O," either of which could
      appear alone on a white computer monitor screen. In baseline series of sessions,
      each form appeared equally often, and two pecks at it produced food reinforcement
      on 10% of trials. Test series varied the relative probability or duration of
      reinforcement or frequency of appearance of the targets. Peck reaction times,
      measured from target onset to the first peck, were found to vary as a function of
      reinforcement probability but not as a function of relative target frequency or
      of reinforcement duration. Reaction times to the two targets remained
      approximately equal as long as the probability of reinforcement, per trial, was
      equal for the targets, even if the relative frequency of the targets differed by
      as much as 19 to 1. The results address issues raised in visual search
      experiments and indicate that attentional priming is unimportant when targets are
      easy to detect. The results also suggest that equalizing reinforcement
      probability per trial for all targets removes differential reinforcement as an
      important variable. That reaction time was sensitive to the probability but not
      the duration of reinforcement raises interesting questions about the processes
      reflected in reaction time compared with rate as a response measure.

PMID- 16812649
TI  - Discriminability between alternatives in a switching-key concurrent schedule.
AB  - Six pigeons were trained to discriminate between two intensities of white light
      in a symbolic matching-to-sample procedure. These stimuli were then used to
      signal which schedule was available on the main key in a switching-key concurrent
      schedule. The concurrent schedules led to a symbolic matching-to-sample phase in
      which the subject identified the concurrent schedule to which it last responded
      before a reinforcer could be obtained. The concurrent schedules were varied
      across conditions. Discriminability, measured during the symbolic matching-to
      sample performance, was high throughout and did not differ across the two
      procedures. Performance in the concurrent schedules was like that typically
      obtained using these schedules. Delays were then arranged between completion of
      the concurrent schedules and presentations of the symbolic matching-to-sample
      phase. A series of conditions with an intervening delay of 10 s showed that both
      concurrent-schedule performance and symbolic matching-to-sample performance were
      affected by the delay in a similar way; that is, choice responding was closer to
      indifference.

PMID- 16812650
TI  - Time-place learning by pigeons, Columba livia.
AB  - In each of two experiments, 2 pigeons received discrimination training in which
      food reinforcement for key pecking was conditional upon both spatial and temporal
      cues. In Experiment 1, food was available for periods of 30 s at each of three
      locations (pecking keys) during trials that lasted 90 s. In Experiment 2, food
      was available for periods of 15 min at each of four locations (pecking keys)
      during a 60-min trial. In both experiments, pigeons' key pecking was jointly
      controlled by the spatial and temporal cues. These data, and other recent
      experiments, suggest that animals learn relationships between temporal and
      spatial cues that predict stable patterns of food availability.

PMID- 16812651
TI  - Application of Herrnstein's hyperbola to time allocation of naturalistic human
      behavior maintained by naturalistic social reinforcement.
AB  - Five college students talked to an experimenter about various topics. Time spent
      looking at the experimenter was reinforced by verbal statements of praise and
      interest on five variable-interval schedules. Herrnstein's hyperbola provided a
      good description of the time-allocation data for 4 of the 5 subjects, and
      accounted for 95% of the variance of the median time-allocation data. The
      hyperbola provided a significantly better description of the data than a two
      parameter ramp function with similar differential properties. Estimates of the
      asymptote, k, of the hyperbola varied among subjects from about 2 to about 15
      seconds of eye contact per minute. These estimates were much smaller than the
      constant 60 seconds of eye contact per minute required by Herrnstein's matching
      theory. These results support the conclusion that Herrnstein's hyperbola
      describes naturalistic human behavior maintained by naturalistic social
      reinforcement as well as it describes the behavior of humans and nonhumans in
      typical laboratory preparations. The results also indicate that the hyperbolic
      form of the time-allocation version of Herrnstein's equation is accurate, but
      that the constant k requirement of matching theory may not hold.

PMID- 16812652
TI  - Human self-control and the density of reinforcement.
AB  - Choice responding in adult humans on a discrete-trial button-pressing task was
      examined as a function of amount, delay, and overall density (points per unit
      time) of reinforcement. Reinforcement consisted of points that were exchangeable
      for money. In T 0 conditions, an impulsive response produced 4 points immediately
      and a self-control response produced 10 points after a delay of 15 s. In T 15
      conditions, a constant delay of 15 s was added to both prereinforcer delays.
      Postreinforcer delays, which consisted of 15 s added to the end of each impulsive
      trial, equated trial durations regardless of choice, and was manipulated in both
      T 0 and T 15 conditions. In all conditions, choice was predicted directly from
      the relative reinforcement densities of the alternatives. Self-control was
      observed in all conditions except T 0 without postreinforcer delays, where the
      impulsive choices produced the higher reinforcement density. These results
      support previous studies showing that choice is a direct function of the relative
      reinforcement densities when conditioned (point) reinforcers are used. In
      contrast, where responding produces intrinsic (immediately consumable)
      reinforcers, immediacy of reinforcement appears to account for preference when
      density does not.

PMID- 16812653
TI  - Real-time detection of orientation during negative behavioral contrast with key
      pecking and a turning response.
AB  - We developed a video system for real-time detection of a pigeon's orientation and
      for reinforcement of a "turning response." Using this system, negative behavioral
      contrast was found across key-peck and turning responses. In addition, turning
      away from the pecking key was detected by the system just after presentation of
      the negative discriminative stimulus on the key. The results suggest that
      avoidance of the discriminative stimulus in the constant component, which has
      been regarded as a causal factor for negative contrast (additivity theory), is
      not the primary factor for negative behavioral contrast of pigeons' key pecking,
      but may account for negative local contrast.

PMID- 16812654
TI  - The dynamics of behavior (Editorial).

PMID- 16812655
TI  - Behavior dynamics: One perspective.
AB  - Behavior dynamics is a field devoted to analytic descriptions of behavior change.
      A principal source of both models and methods for these descriptions is found in
      physics. This approach is an extension of a long conceptual association between
      behavior analysis and physics. A theme common to both is the role of molar versus
      molecular events in description and prediction. Similarities and differences in
      how these events are treated are discussed. Two examples are presented that
      illustrate possible correspondence between mechanical and behavioral systems. The
      first demonstrates the use of a mechanical model to describe the molar properties
      of behavior under changing reinforcement conditions. The second, dealing with
      some features of concurrent schedules, focuses on the possible utility of
      nonlinear dynamical systems to the description of both molar and molecular
      behavioral events as the outcome of a deterministic, but chaotic, process.

PMID- 16812656
TI  - Resistance to change and the law of effect.
AB  - Three experiments using multiple schedules of reinforcement explored the
      implications of resistance-to-change findings for the response-reinforcer
      relation described by the law of effect, using both steady-state responding and
      responding recorded in the first few sessions of conditions. In Experiment 1,
      when response-independent reinforcement was increased during a third component,
      response rate in Components 1 and 2 decreased. This response-rate reduction was
      proportionately greater in a component in which reinforcer magnitude was small (2
      s access to wheat) than in the component in which it was large (6-s access to
      wheat). However, when reinforcer rates in the two components were varied together
      in Experiments 2 and 3, response-rate change was the same regardless of the
      magnitude of reinforcers used in the two components, so that sensitivity of
      response rates to reinforcer rates (Experiment 2) and of response-rate ratios to
      reinforcer-rate ratios (Experiment 3) was unaffected by the magnitude of the
      reinforcers. Therefore, the principles determining resistance to change,
      described by behavioral momentum theory, seem not to apply when the source of
      behavior change is the variation of reinforcement contingencies that maintain the
      behavior. The use of extinction as a manipulation to study resistance to change
      is questioned.

PMID- 16812657
TI  - Order and chaos in fixed-interval schedules of reinforcement.
AB  - Fixed-interval schedule performance is characterized by high levels of
      variability. Responding is absent at the onset of the interval and gradually
      increases in frequency until reinforcer delivery. Measures of behavior also vary
      drastically and unpredictably between successive intervals. Recent advances in
      the study of nonlinear dynamics have allowed researchers to study irregular and
      unpredictable behavior in a number of fields. This paper reviews several concepts
      and techniques from nonlinear dynamics and examines their utility in predicting
      the behavior of pigeons responding to a fixed-interval schedule of reinforcement.
      The analysis provided fairly accurate a priori accounts of response rates,
      accounting for 92.8% of the variance when predicting response rate 1 second in
      the future and 64% of the variance when predicting response rates for each second
      over the entire next interreinforcer interval. The nonlinear dynamics account
      suggests that even the "noisiest" behavior might be the product of purely
      deterministic mechanisms.

PMID- 16812658
TI  - In search of the feedback function for variable-interval schedules.
AB  - Finding a theoretically sound feedback function for variable-interval schedules
      remains an important unsolved problem. It is important because interval schedules
      model a significant feature of the world: the dependence of reinforcement on
      factors beyond the organism's control. The problem remains unsolved because no
      feedback function yet proposed satisfies all the theoretical and empirical
      requirements. Previous suggestions that succeed in fitting data fail
      theoretically because they violate a newly recognized theoretical requirement:
      The slope of the function must approach or equal 1.0 at the origin. A function is
      presented that satisfies all requirements but lacks any theoretical
      justification. This function and two suggested by Prelec and Herrnstein (1978)
      and Nevin and Baum (1980) are evaluated against several sets of data. All three
      fitted the data well. The success of the two theoretically incorrect functions
      raises an empirical puzzle: Low rates of reinforcement are coupled with response
      rates that seem anomalously high. It remains to be discovered what this reflects
      about the temporal patterning of operant behavior at low reinforcement rates. A
      theoretically and empirically correct function derived from basic assumptions
      about operant behavior also remains to be discovered.

PMID- 16812659
TI  - Applying linear systems analysis to dynamic behavior.
AB  - In this paper we present an abbreviated discussion of the linear systems analysis
      in the time domain. We then consider the qualitative character of the behavioral
      dynamics predicted using the linear form of the analysis. The analysis is then
      extended to a second-order form. We illustrate some relevant new features
      introduced by the second-order form with a special case example.

PMID- 16812660
TI  - On immediate function.
AB  - Behavior is a property of living organisms, not of inanimate matter. The problems
      of physical science are to understand how a phenomenon works; biological science
      adds the questions of what a phenomenon does and how something that does such
      things came to be. Exclusive dedication to cause-effect explanations ignores how
      behavior helps creatures cope with their internal and external environments. Laws
      of causation describe the precursors to behavior; laws of function describe the
      effects of behavior. The numerous instances of learning reflect the many ways
      that selective pressure for altering behavior on the basis of experience has been
      manifested. Little basis exists for assuming that the various forms of learning
      reflect either common functions or common processes. Instead, it seems that
      evolutionary processes have resulted in domain-specific learning. The rules of
      learning must be understood in terms of the function that the particular
      manifestation of learning serves for the organism. Evolutionary theory provides
      the framework for understanding function as well as relations between function
      and causal mechanisms.

PMID- 16812661
TI  - Discriminative performance of the domestic hen in a visual acuity task.
AB  - The performance of 6 domestic hens on a visual acuity task was studied using a
      spatial discrete-trial conditional discrimination procedure. Gray stimuli and
      vertical square-wave gratings, ranging in spatial frequency from 1 to 10 cycles
      per millimeter, were presented in a descending and ascending series of probes. On
      each trial, either a grating or gray stimulus was presented. Only one spatial
      frequency of grating was presented during each session. Between probe sessions,
      training continued at the coarsest grating value. Stimulus discriminability,
      measured as values of log d, changed with changes in grating spatial frequency
      for both probe series. Fitted lines described the linear portion of the
      psychometric functions. Thresholds estimated from the lines generally ranged from
      four to six cycles per degree, with slightly greater estimates from data from the
      descending probe series. There were no systematic changes in response bias as a
      function of grating spatial frequency.

PMID- 16812662
TI  - Sample-stimulus discriminability and sensitivity to reinforcement in delayed
      matching to sample.
AB  - Five pigeons were trained in a delayed matching-to-sample task with red and green
      stimuli. The retention interval between sample-stimulus presentation and the
      availability of the choice stimuli was varied between 0.01 s and 12 s within each
      session. The probability of food produced by correct-red and correct-green
      responses was varied across conditions. Sample-stimulus discriminability and
      response bias were measured at four different retention intervals. The results of
      these analyses showed an interaction between the discriminability of the sample
      stimuli and the control exerted by differential reinforcement. At longer
      retention intervals, sample discriminability decreased and sensitivity of choice
      behavior to changes in the red/green reinforcer ratio increased. An analogous
      relation has been reported in conditional discriminations in which the physical
      disparity of stimuli has been varied. This correspondence suggests that
      increasing the delay between presentation of one of two stimuli and an
      opportunity to respond discriminatively to it may be functionally similar to
      increasing the physical similarity of the two stimuli.

PMID- 16812663
TI  - Conditional discrimination and equivalence relations: A theoretical analysis of
      control by negative stimuli.
AB  - A detailed analysis is presented of the ways in which control by the negative
      stimulus in two-comparison conditional discriminations may be expected to affect
      the outcome of tests for the properties of equivalence relations. Control by the
      negative stimulus should produce the following results: (a) no observable effect
      on symmetry tests; (b) reflexivity test results should look like "oddity" rather
      than "identity"; and (c) transitivity tests that involve an odd number of nodes
      should yield results that are 100% opposite to tests that involve an even number
      of nodes. The analysis also considers the effects of variation in the type of
      comparison-stimulus control between and within baseline conditional
      discriminations. Methods are suggested for experimentally regulating the type of
      control, and for verifying the predictions that the analysis generates. If
      suggested experiments continue to support the analysis, investigators who use two
      comparison conditional discriminations to study equivalence relations will either
      have to control explicitly whether the positive or the negative comparison
      governs their subjects' choices, or they will have to abandon two comparisons and
      use three or more comparisons instead.

PMID- 16812664
TI  - Continuous versus discrete dimensions of reinforcement schedules: An integrative
      analysis.
AB  - An approach to reinforcement-schedule contingencies is presented that
      accommodates continuous as well as discrete effective dimensions of responses and
      reinforcers. College students' wheel turning was reinforced by projected reading
      material according to four schedule contingencies that incorporated either a
      discontinuous (count) or continuous (duration) dimension of the response and the
      reinforcer. The contingencies arranged a 1:1 correspondence between (a) response
      count and consequent stimulus count, (b) response duration and stimulus count,
      (c) response count and stimulus duration, and (d) response duration and stimulus
      duration. Contingencies incorporating response count produced moderate to high
      rates of very short-duration responses. Contingencies incorporating response
      duration produced very low-rate, long-duration responding. The dimension of the
      reinforcer had minimal or no additional effect. We suggest that incorporating
      duration and other continuous dimensions into schedule contingencies may improve
      our understanding of both laboratory and nonlaboratory behavior.

PMID- 16812665
TI  - Choice between fixed-interval schedules: Graded versus step-like choice
      functions.
AB  - Pigeons chose between two fixed-interval schedules of food reinforcement. A
      single peck on one of two lighted keys started the fixed-interval schedule
      correlated with that key. The schedule had to be completed before the next choice
      opportunity. The durations of the fixed intervals were varied over conditions
      from 15 s to 40 s. To maximize the rate of reinforcement, the pigeons had to
      choose exclusively the shorter of the two schedules. Nevertheless, choice was not
      all-or-none. Instead, relative choice, and the rates of producing the fixed
      intervals, varied in a graded fashion with the disparity between the two
      schedules. Choice ratios under this procedure (single response to choose) were
      highly sensitive to the ratios of the fixed-interval schedules.

PMID- 16812666
TI  - The autoshaping procedure as a residual block clock.
AB  - In the first experiment, 4 pigeons were each presented with a recurring sequence
      of four key colors followed by the delivery of grain (block clock). Once the rate
      of pecking had stabilized, three of the colors were replaced, during different
      series of sessions, by a darkening of the key. The rate of pecking was reduced
      within those segments of the interval between deliveries of food during which the
      key was dark; when the key was dark during the final portion of the interval,
      rates were reduced throughout the entire interval. In the second experiment, 3
      new pigeons were exposed to a different sequence of colors, and the final
      stimulus was replaced in successive conditions by a novel color, a darkened key,
      and a restoration of the original color. The data indicated that darkening the
      key had a more severe, more extensive, and more persistent effect than did a mere
      change in color. These results suggest that it may be fruitful to conceptualize
      the autoshaping procedure as a special version of the block clock in which
      pecking is suppressed throughout the greater part of the interval by darkening
      the key. In the final condition, the same stimulus appeared in each of the last
      three portions of the interval. The rate of pecking was lower during the last two
      portions than when distinctive colors were presented, with the peak rate now
      appearing in the fifth of seven equal temporal components.

PMID- 16812667
TI  - Inverse relations between preference and contrast.
AB  - Pigeons were trained on a multiple schedule in which two target components with
      identical reinforcement schedules were followed by either the same-valued
      schedule or by extinction. Response rate increased in both target components but
      was higher in the target component followed by extinction, replicating previous
      findings of positive anticipatory contrast. A similar design was used to study
      negative contrast, in that the two target components were followed either by the
      same-valued schedule or by a higher valued schedule. Negative contrast occurred
      equally, on average, in both target components, thus failing to demonstrate
      negative contrast that is specifically anticipatory in nature. When the stimuli
      correlated with the two target components were paired in choice tests, the
      pattern of preference was in the opposite direction. For the positive contrast
      procedure, no significant preference between the two target stimuli was evident.
      But for the negative contrast procedure, preference favored the stimulus followed
      by the higher valued schedule. The results demonstrate a functional dissociation
      between positive and negative contrast in relation to stimulus value. More
      generally, the results demonstrate an inverse relation between response rate and
      preference and challenge existing accounts of contrast in terms of the concept of
      relative value.

PMID- 16812668
TI  - Maximizing versus matching on concurrent variable-interval schedules.
AB  - Maximization and matching predictions were examined for a time-based analogue of
      the concurrent variable-interval variable-ratio schedule. One alternative was a
      variable interval whose time base operated relatively independent of the schedule
      chosen, and the other was a discontinuous variable interval for which timing
      progressed only when selected. Pigeons switched between schedules by pecking a
      changeover key. The maximization hypothesis predicts that subjects will show a
      bias toward the discontinuous variable interval and undermatching; however the
      obtained results conformed closely to the predictions of the matching law.
      Finally, a quantitative comparison was made of the bias and sensitivity estimates
      obtained in published concurrent variable-interval variable-ratio analogue
      studies. Results indicated that only the ratio-based analogue of the concurrent
      variable interval variable ratio studied by Green, Rachlin, and Hanson (1983)
      produced significant bias toward the variable-ratio alternative and
      undermatching, as predicted by reinforcement maximization.

PMID- 16812669
TI  - Stimulus effects on concurrent performance in transition.
AB  - Six experimentally naive pigeons were exposed to concurrent variable-interval
      variable-interval schedules in a three-key procedure in which food reinforcement
      followed pecks on the side keys and pecks on the center key served as changeover
      responses. In Phase 1, 3 birds were exposed to 20 combinations of five variable
      interval values, with each variable-interval value consistently associated with a
      different color on the side keys. Another 3 pigeons were exposed to the same 20
      conditions, but with a more standard procedure that used a nondifferential
      discriminative stimulus on the two side keys throughout all conditions. In Phase
      2, the differential and nondifferential stimulus conditions were reversed for
      each pigeon. Each condition lasted for one 5-hr session and one subsequent 1-hr
      session. In the last 14 conditions of each phase, the presence of differential
      discriminative stimuli decreased the time necessary for differential responding
      to develop and increased the sensitivity of behavior to reinforcement
      distribution in the 1st hr of training; during the last hours of training in each
      condition, however, the effects of the differential discriminative stimuli could
      not be distinguished from the effects of reinforcement distribution per se. These
      results show the importance of studying transitions in behavior as well as final
      performance. They may also be relevant to discrepancies in the results of
      previous experiments that have used nonhuman and human subjects.

PMID- 16812670
TI  - Molecular contingencies in schedules of intermittent punishment.
AB  - In two experiments, key pecking of pigeons was maintained by a variable-interval
      180-s schedule of food presentation. Conjointly, a second schedule delivered
      response-dependent electric shock. In the first experiment, shocks were presented
      according to either a variable-interval or a nondifferential interval-percentile
      schedule. The variable-interval shock schedule differentially delivered shocks
      following long interresponse times. Although the nondifferential shock schedules
      delivered shocks less differentially with respect to interresponse times, the two
      shock schedules equally reduced the relative frequency of long interresponse
      times. The second experiment differentially shocked long or short interresponse
      times in different conditions, with resulting decreases in the relative frequency
      of the targeted interresponse times. These experiments highlight the importance
      of selecting the appropriate level of analysis for the interaction of behavior
      and environment. Orderly relations present at one level of analysis (e.g.,
      interresponse times) may not be revealed at other levels of analysis (e.g.,
      overall response rate).

PMID- 16812671
TI  - Reinforcement magnitude and pausing on progressive-ratio schedules.
AB  - Rats responded under progressive-ratio schedules for sweetened milk reinforcers;
      each session ended when responding ceased for 10 min. Experiment 1 varied the
      concentration of milk and the duration of postreinforcement timeouts.
      Postreinforcement pausing increased as a positively accelerated function of the
      size of the ratio, and the rate of increase was reduced as a function of
      concentration and by timeouts of 10 s or longer. Experiment 2 varied
      reinforcement magnitude within sessions (number of dipper operations per
      reinforcer) in conjunction with stimuli correlated with the upcoming magnitude.
      In the absence of discriminative stimuli, pausing was longer following a large
      reinforcer than following a small one. Pauses were reduced by a stimulus
      signaling a large upcoming reinforcer, particularly at the highest ratios, and
      the animals tended to quit responding when the past reinforcer was large and the
      stimulus signaled that the next one would be small. Results of both experiments
      revealed parallels between responding under progressive-ratio schedules and other
      schedules containing ratio contingencies. Relationships between pausing and
      magnitude suggest that ratio pausing is under the joint control of inhibitory
      properties of the past reinforcer and excitatory properties of stimuli correlated
      with the upcoming reinforcer, rather than under the exclusive control of either
      factor alone.

PMID- 16812672
TI  - Schedule-induced defecation: No-food and massed-food baselines.
AB  - Defecation rate was monitored during daily 30-min periods as 16 rats were exposed
      to different sequences of the following three experimental conditions: (a) a
      fixed-time 60-s food delivery schedule, (b) a massed-food presentation baseline,
      and/or (c) a no-food baseline. All food delivery was response independent. Rate
      of defecation increased during fixed-time 60-s food delivery when compared to
      baseline rates of defecation established during no-food and massed-food
      baselines. This effect was present for 12 of 16 rats during four alternative
      sequences of experimental conditions. Within-subject reversals established
      reliability of this effect. Schedule induction of defecation is clearly
      demonstrated under these conditions.

PMID- 16812673
TI  - Inelastic supply: An economic approach to simple interval schedules.
AB  - Economic theory predicts an inverse relationship between the quantity of a
      commodity supplied to the marketplace and the equilibrium market price of that
      commodity. This prediction was tested in three experiments. Pigeons responded on
      simple variable-interval schedules, and quantity of reinforcement supplied was
      varied in a different way in each experiment. In Experiment 1, quantity supplied
      was varied by manipulating reinforcement rate while keeping session length
      constant. In Experiment 2, quantity supplied was varied by manipulating
      reinforcement rate while keeping reinforcers per session constant. In Experiment
      3, quantity supplied was varied by manipulating reinforcer magnitude while
      keeping number of reinforcers constant. As predicted by economic theory, the
      obtained behavioral cost (responses per reinforcer) increased as supply
      decreased. The results could not be explained by simple artifacts such as
      satiation and time available to respond. In addition, the function relating
      response rate to reinforcement rate was bitonic in 7 of 9 animals in Experiments
      1 and 2, which supports economic and regulatory theories over more traditional
      reinforcement theories.

PMID- 16812674
TI  - Acquisition of lever-press responding in rats with delayed reinforcement: A
      comparison of three procedures.
AB  - The present study examined the acquisition of lever pressing in rats under three
      procedures in which food delivery was delayed by 4, 8, and 16 seconds relative to
      the response. Under the nonresetting delay procedure, food followed the response
      selected for reinforcement after a specified interval elapsed; responses during
      this interval had no programmed effect. Under the resetting procedure, the
      response selected for reinforcement initiated an interval to food delivery that
      was reset by each subsequent response. Under the stacked delay procedure, every
      response programmed delivery of food t seconds after its occurrence. Two control
      groups were studied, one that received food immediately after each lever press
      and another that never received food. With the exception of the group that did
      not receive food, responding was established with every procedure at every delay
      value without autoshaping or shaping. Although responding was established under
      the resetting delay procedure, response rates were generally not as high as under
      the other two procedures. These findings support the results of other recent
      investigations in demonstrating that a response not previously reinforced can be
      brought to strength by delayed reinforcement in the absence of explicit training.

PMID- 16812675
TI  - Choice between repleting/depleting patches: A concurrent-schedule procedure.
AB  - Six pigeons responded on two concurrently available keys that defined patches
      with the following characteristics. Reinforcer stores repleted on a patch as a
      linear function of time when the bird had last responded to the other patch, or
      else did not replete. Repletion schedules thus timed only when the bird was
      absent from the patch. Reinforcer stores on a patch could be depleted and
      reinforcers obtained, again as a linear function of time, when the bird responded
      on a key. Depletion schedules thus timed only when the birds were present at a
      patch. Experiment 1 investigated changing relative depletion rates when repletion
      rates were constant and equal (Part 1) and changing relative repletion rates when
      the depletion rates were constant and equal (Part 2). Response- and time
      allocation ratios conformed to a generalized matching relation with obtained
      reinforcer ratios, and there appeared to be no control by the size of the
      reinforcer stores. In Experiment 2, absolute depletion rates were varied with a
      pair of unequal repletion rates (Part 3), and absolute repletion rates were
      varied with a pair of unequal depletion rates (Part 4). Dwell times in the
      patches were not affected by either variation. Melioration theory predicted the
      results of Experiment 1 quite closely but erroneously predicted changing dwell
      times in Experiment 2. Molar maximization theory did not accurately predict the
      results of either experiment.

PMID- 16812676
TI  - Reductions in shock frequency and response effort as factors in reinforcement by
      timeout from avoidance.
AB  - Rats' presses on one lever canceled shocks programmed after variable cycles,
      while presses on a second lever occasionally produced a 2-min timout during which
      the shock-delection schedule was suspended and its correlated stimuli removed.
      These concurrent schedules of avoidance and timeout were embedded in a multiple
      schedule whose components differed, within and across conditions, in terms of the
      programmed shock rate associated with the shock-deletion schedule. Analyses based
      on the generalized matching law suggest that the reduction in the response
      requirement correlated with termination of the avoidance schedule was a more
      important factor in the reinforcing effectiveness of timeout than was shock
      frequency reduction, at least in 2 of 3 rats. After training in each condition,
      responding on the timeout lever was extinguished by withholding timeouts in both
      components over seven sessions. Resistance to extinction varied directly with the
      rates of both shock-frequency reduction and avoidance-response reduction
      experienced during training. Although reduction in response effort appeared to
      dominate shock-frequency reduction in the maintenance of responding, neither
      factor had a clear advantage in predicting the course of extinction.

PMID- 16812677
TI  - Contrast and reallocation of extraneous reinforcers between multiple-schedule
      components.
AB  - Four pigeons responded in components of multiple schedules in which two responses
      were available and reinforced with food. Pecks on the left key ("main" key) were
      reinforced at a constant rate in one component and at a rate that varied over
      conditions in the other component. When reinforcer rate was varied, behavioral
      contrast occurred in the constant component. On the right key ("extra" key), five
      variable-interval schedules and one variable-ratio schedule, presented
      conjointly, arranged reinforcers for responses in all conditions. These conjoint
      schedules were common to both multiple-schedule components-rather than unique to
      particular components-and reinforcers from these schedules could therefore be
      arranged in one component and obtained during the other component. In this way,
      the additional reinforcers were analogous to the "extraneous" reinforcers thought
      to maintain behavior other than pecking in conventional multiple schedules.
      Response rate on the extra key did not change systematically over conditions in
      the constant component, and in the varied component extra responding was
      inversely related to main-key reinforcement. All subjects obtained more extra-key
      reinforcers in whichever component arranged fewer main-key reinforcers.
      Consistent with the theory that reallocation of extraneous reinforcers may cause
      behavioral contrast, absolute reinforcer rate for the extra key in the constant
      component was low in conditions that produced positive contrast on the main key
      and high in those that produced negative contrast. Also consistent with this
      theory, behavioral contrast was reduced in two conditions that canceled extra-key
      reinforcers that had been arranged but not obtained at the end of components.
      Thus, a constraint on reallocation markedly reduced the extent of contrast.

PMID- 16812678
TI  - Sequences of spaced responses: Behavioral units and the role of contiguity.
AB  - Sequences of temporally spaced responses were reinforced to investigate the
      effects of delay of reinforcement on the formation of functional behavioral
      units. In Experiment 1, rats' two- and three-response demarcated sequences of
      left and right lever presses were reinforced such that different response
      distributions would occur depending on whether the sequences themselves or
      individual responses were functional units. The matching law could thus be obeyed
      either by individual responses or by sequences, but not by both; intermediate
      results were possible. Both regular (nonretractable) and retractable levers were
      used; the retractable levers precluded the occurrence of insufficiently spaced
      responses. At a minimum interresponse time of 5 s for regular levers and 7 s for
      retractable ones, matching results were intermediate, with greater evidence of
      sequence conditionability in the two-response sequences than in the three
      response sequences. In Experiment 2, the required minimum interresponse spacing
      for two-response retractable-lever sequences was varied in an attempt to locate
      the sequence matching threshold. This attempt was unsuccessful, but the sequences
      (instead of individual responses) more closely obeyed the matching law. In the
      shortest spaced condition, conditional probability data on Lag 1 sequence
      emission order showed marked, highly similar patterning for all rats, indicating
      sequential control of the sequences. Post hoc definition of the behavioral unit
      in these studies is ambiguous. Although reinforcement contiguity was important,
      aspects of the results could support both molar- and molecular-level
      interpretations.

PMID- 16812679
TI  - Conditioned reinforcement of human observing behavior by descriptive and
      arbitrary verbal stimuli.
AB  - College students earned monetary reinforcers by pressing a key according to a
      compound schedule with variable-interval and extinction components. Pressing
      additional keys occasionally produced displays of either of two verbal stimuli;
      one was uncorrelated with the schedule components, and the other was correlated
      with the extinction component. In Experiments 1 and 2, the display area of the
      apparatus was blank unless an observing key was pressed, whereupon a descriptive
      message appeared. Most students preferred an uncorrelated stimulus stating that
      "Some of this time scores are TWICE AS LIKELY as normal, and some of this time NO
      SCORES can be earned" over a stimulus stating that "At this time NO SCORES can be
      earned." In Experiment 3, the display area indicated that "The Current Status of
      the Program is: NOT SHOWN." Presses on the observing keys replaced this message
      with stimuli that provided arbitrary labels for the schedule conditions. All of
      the students preferred a stimulus stating that "The Current Status of the Program
      is: B" over an uncorrelated stimulus stating that "The Current Status of the
      Program is: either A or B." Thus, under some circumstances, observing was
      maintained by a stimulus correlated with extinction-a finding that poses a
      challenge for Pavolvian accounts of conditioned reinforcement. Differences in the
      maintenance of observing by the descriptive and arbitrary stimuli may be
      attributed to differences in either the strength or nature of the instructional
      control exerted by the verbal stimuli.

PMID- 16812680
TI  - Motion as a natural category for pigeons: Generalization and a feature-positive
      effect.
AB  - Three groups of pigeons were trained with a modified discriminative autoshaping
      procedure to discriminate video images of other pigeons on the basis of movement.
      Birds of all groups were shown the same video images of other pigeons, which were
      either moving or still. The group to whom food was presented only after moving
      images learned the discrimination very quickly. A second group, to whom food was
      given only after still images, and a pseudocategory group, to whom food was
      presented after arbitrarily chosen stimuli, showed no evidence of discrimination
      during acquisition training. Extinction conditions led to clear differences in
      peck rates to moving and still images in the second group but not in the
      pseudocategory group. The result is related to the feature-positive effect.
      Generalization tests showed that the discrimination performance was based on
      visual features of the stimuli but was invariant against changes of size,
      perspective, brightness, and color. Furthermore, discrimination was maintained
      when novel images of pigeons under different viewing angles and seven other types
      of motion categories were presented. It is argued that the discrimination is
      based not on a common motion feature but on motion concepts or high-order
      generalization across motion categories.

PMID- 16812681
TI  - Removal of an obstacle: Problem-solving behavior in pigeons.
AB  - The importance of a subject's personal history in the solution of an obstruction
      problem was demonstrated with pigeons. Four birds were trained to peck a key
      located outside the chamber by poking their heads through an opening in a screen.
      During tests, a white block was placed in front of the opening, so that it was
      not possible to peck the key without removing the block. All birds failed to
      remove the block. However, all birds that were subsequently trained to push the
      white block around the chamber in the absence of the key and a few of the birds
      trained similarly but with a black block solved the problem by pushing the block
      aside and pecking the key. One bird showed the abrupt descent in the learning
      curve that has been considered a characteristic of "insightful" problem solving.
      All birds maintained their successful performance after a 1-month interval with
      no intervening tests.

PMID- 16812682
TI  - Effects of differences between stimuli, responses, and reinforcer rates on
      conditional discrimination performance.
AB  - In a discrete-trial conditional discrimination procedure, 4 pigeons obtained food
      reinforcers by pecking a key with a short latency on trials signaled by one
      stimulus and by pecking the same key with a long latency on trials signaled by a
      second stimulus. The physical difference between the two stimuli and the temporal
      separation between the latency values required for reinforcement were varied
      factorially over four sets of conditions, and the ratio of reinforcer rates for
      short and long latencies was varied within each set of conditions. Stimulus
      discrimination varied directly with both stimulus and response differences and
      was unaffected by the reinforcer ratio. Sensitivity to reinforcement, estimated
      by generalized-matching-law fits to the data within each set of conditions,
      varied directly with the response difference but inversely with the stimulus
      difference arranged between sets of conditions. Because variations in stimulus
      differences, response differences, and reinforcer differences did not have
      equivalent effects, these findings question the functional equivalence of the
      three terms of the discriminated operant: antecedent stimuli, behavior, and
      consequences.

PMID- 16812683
TI  - The effects of response cost and response restriction on a multiple-response
      repertoire with humans.
AB  - In two experiments a multiple-response repertoire of four free-operant responses
      was developed with university students as subjects using monetary gain as
      reinforcement. Following baseline, one of the responses was reduced either by
      making monetary loss contingent upon it (response cost) or by removing it from
      the repertoire (response restriction). In Experiment 1 a multielement baseline
      design was employed in which baseline and restriction or response-cost
      contingencies alternated semirandomly every 3 minutes. In Experiment 2 a reversal
      design was employed (i.e., baseline, restriction or response cost, then
      baseline), and each response required a different amount of effort. Both
      experiments had the following results: (a) The target response decreased
      substantially; (b) most nontarget responses increased, and the rest remained near
      their baseline levels; and (c) no support was found for Dunham's hierarchical,
      most frequent follower, or greatest temporal similarity rules. For several
      subjects, the least probable responses during baseline increased most, and the
      most probable responses increased least. Furthermore, in Experiment 2, responses
      with the lowest frequency of reinforcement increased most (for all 7 subjects),
      and those with the greatest frequency of reinforcement increased least (for 5
      subjects).

PMID- 16812684
TI  - Response-reinforcer independence and the economic continuum: A preliminary
      analysis.
AB  - Three pigeons were exposed to 1-hr and 4-hr sessions during which they earned
      food under a fixed-ratio 50 schedule of reinforcement while obtaining additional
      food according to either a variable-interval or a variable-time schedule.
      Postsession food was provided after the 1-hr sessions. The frequency of the
      variable-interval and variable-time food presentations was varied under the two
      session durations. The various combinations of within-session earned and unearned
      food, as well as the postsession food, defined conditions on the open-to-closed
      economy continuum. Key pecks tended to increase as the frequency of either
      variable-interval or variable-time food decreased. An economic-continuum analysis
      based on an independence quotient as a measure of response-reinforcer
      independence is presented to account for the effects.

PMID- 16812685
TI  - A transfer of functions through derived arbitrary and nonarbitrary stimulus
      relations.
AB  - During Experiments 1 and 2, subjects were trained in a series of related
      conditional discriminations in a matching-to-sample format (A1-B1, A1-C1 and A2
      B2, A2-C2). A low-rate performance was then explicitly trained in the presence of
      B1, and a high-rate performance was explicitly trained in the presence of B2. The
      two types of schedule performance transferred to the C stimuli for all subjects
      in both experiments, in the absence of explicit reinforcement through equivalence
      (i.e., C1 = low rate and C2 = high rate). In Experiment 2, it was also shown that
      these discriminative functions transferred from the C1-C2 stimuli to two novel
      stimuli that were physically similar to the C stimuli (SC1 and SC2,
      respectively). For both these experiments, subjects demonstrated the predicted
      equivalence responding during matching-to-sample equivalence tests. In
      Experiments 3 and 4, the conditional discrimination training from the first two
      experiments was modified in that two further conditional discrimination tasks
      were trained (C1-D1 and C2-D2). However, for these tasks the D stimuli served
      only as positive comparisons, and ND1 and ND2 stimuli served as negative
      comparisons (i.e., C1 x ND1 and C2 x ND2). Subsequent to training, the negatively
      related stimuli (ND1 and ND2) did not become discriminative for the schedule
      performances explicitly trained in the presence of B1 and B2, respectively.
      Instead, the ND1 stimulus became discriminative for the schedule performance
      trained in the presence of B2, and ND2 became discriminative for the schedule
      performance trained in the presence of B1. All subjects from Experiment 4 showed
      that the novel stimulus SND1, which was physically similar to ND1, became
      discriminative for the same response pattern as that controlled by ND1.
      Similarly, SND2, which was physically similar to ND2, became discriminative for
      the same response pattern as that controlled by ND2. Subjects from both
      Experiments 3 and 4 also produced equivalence responding on matching-to-sample
      equivalence tests that corresponded perfectly to the derived performances shown
      on the transfer of discriminative control tests.

PMID- 16812686
TI  - Performances on ratio and interval schedules of reinforcement: Data and theory.
AB  - TWO DIFFERENCES BETWEEN RATIO AND INTERVAL PERFORMANCE ARE WELL KNOWN: (a) Higher
      rates occur on ratio schedules, and (b) ratio schedules are unable to maintain
      responding at low rates of reinforcement (ratio "strain"). A third phenomenon, a
      downturn in response rate at the highest rates of reinforcement, is well
      documented for ratio schedules and is predicted for interval schedules. Pigeons
      were exposed to multiple variable-ratio variable-interval schedules in which the
      intervals generated in the variable-ratio component were programmed in the
      variable-interval component, thereby "yoking" or approximately matching
      reinforcement in the two components. The full range of ratio performances was
      studied, from strained to continuous reinforcement. In addition to the expected
      phenomena, a new phenomenon was observed: an upturn in variable-interval response
      rate in the midrange of rates of reinforcement that brought response rates on the
      two schedules to equality before the downturn at the highest rates of
      reinforcement. When the average response rate was corrected by eliminating
      pausing after reinforcement, the downturn in response rate vanished, leaving a
      strictly monotonic performance curve. This apparent functional independence of
      the postreinforcement pause and the qualitative shift in response implied by the
      upturn in variable-interval response rate suggest that theoretical accounts will
      require thinking of behavior as partitioned among at least three categories, and
      probably four: postreinforcement activity, other unprogrammed activity, ratio
      typical operant behavior, and interval-typical operant behavior.

PMID- 16812687
TI  - Short-term and long-term effects of reinforcers on choice.
AB  - The relation between molar and molecular aspects of time allocation was studied
      in pigeons on concurrent variable-time variable-time schedules of reinforcement.
      Fifteen-minute reinforcer-free periods were inserted in the middle of every third
      session. Generalized molar matching of time ratios to reinforcer ratios was
      observed during concurrent reinforcement. Contrary to melioration theory,
      preference was unchanged during the reinforcer-free periods as well as in
      extinction. In addition to this long-term effect of reinforcement, short-term
      effects were observed: Reinforcers increased the duration of the stays during
      which they were delivered but had little consistent effect either on the
      immediately following stay in the same schedule or on the immediately following
      stay in the alternative schedule. Thus, an orderly effect of reinforcer delivery
      on molecular aspects of time allocation was observed, but because of its short
      term nature, this effect cannot account for the matching observed at the molar
      level.

PMID- 16812688
TI  - Testing a stochastic foraging model in an operant simulation: Agreement with
      qualitative but not quantitative predictions.
AB  - An operant simulation of foraging through baited and empty patches was studied
      with 4 pigeons. On a three-key panel, side keys were designated as patches, and
      successive opportunities to complete 16 fixed-ratio 10 schedules on side keys
      were defined as encounters with feeders. In a random half of the patches in any
      session, some of the fixed-ratio 10 schedules yielded reinforcement (baited
      feeders) and the other schedules yielded nonreinforcement (empty feeders). In the
      other half of the patches, all feeders were empty. Pigeons could travel between
      patches at any time by completing a fixed-ratio schedule on the center key. An
      optimal foraging model was tested in Experiments 1 and 2 by varying center-key
      travel time and number of baited feeders in baited patches. The ordinal
      predictions that number of feeders visited in empty patches would increase with
      travel time and decrease as number of baited feeders increased were supported,
      but pigeons visited far more feeders in empty patches than the optimal number
      predicted by the model to maximize energy/time. In Experiment 3, evidence was
      found to suggest that the number of empty feeders encountered before the first
      baited feeder in baited patches is an important factor controlling leaving empty
      patches.

PMID- 16812689
TI  - Conditional discrimination and equivalence relations: Control by negative
      stimuli.
AB  - Three adult subjects were taught the following two-sample, two-comparison
      conditional discriminations (each sample is shown with its positive and negative
      comparison, in that order): A1-B1B2, A2-B2B1; B1-C1C2, B2-C2C1; and C1-D1D2, C2
      D2D1. A teaching procedure was designed to encourage control by negative
      comparisons. Subjects were then tested for emergent performances that would
      indicate whether the baseline conditional discriminations were reflexive,
      symmetric, and transitive. The tests documented the emergence of two classes of
      equivalent stimuli: A1, B2, C1, D2 and A2, B1, C2, D1. These were the classes to
      be expected if the negative comparisons were the controlling comparisons in the
      baseline conditional discriminations. The negative comparisons, however, were not
      the comparisons that subjects were recorded as having chosen in the baseline
      conditional discriminations. Differential test results confirmed predictions
      arising from a stimulus-control analysis: In reflexivity tests (AA, BB, CC, DD),
      subjects chose comparisons that differed from the sample; one-node transitivity
      (AC, BD) and "equivalence" (CA, DB) tests also yielded results that were the
      opposite of those to be expected from control by positive comparisons; symmetry
      tests (BA, CB, DC), two-node transitivity (AD) tests, and two-node "equivalence"
      (DA) tests yielded results that were to be expected from control by either
      positive or negative comparisons.

PMID- 16812690
TI  - Choice and delay of reinforcement: Effects of terminal-link stimulus and response
      conditions.
AB  - In two experiments, pigeons were exposed to concurrent-chains schedules in which
      a single initial-link variable-interval schedule led to access to terminal links
      composed of fixed-interval or fixed-delay schedules. In Experiment 1, an 8-s (or
      16-s) delay to reinforcement was associated with the standard key, while
      reinforcer delay values associated with the experimental key were varied from 4
      to 32 s. The results of Experiment 1 showed undermatching of response ratios to
      delay ratios with terminal-link fixed-delay schedules, whereas in some pigeons
      matching or overmatching was evident with the fixed-interval schedules. In
      Experiment 2, one pair of reinforcer delay values, either 8 versus 16 s or 16
      versus 32 s, was used. In the first condition of Experiment 2, different delays
      were associated with different keylight stimuli (cued condition). In the second
      condition, different terminal-link delays were associated with the same stimulus,
      either a blackout (uncued-blackout condition) or a white key (uncued-white
      condition). To examine the role of responses emitted during delays, the keys were
      retracted during a delay (key-absent condition) in the third condition and
      responses were required by a fixed-interval schedule in the fourth condition.
      Experiment 2 demonstrated that the choice proportions for the shorter delay were
      more extreme in the cued condition than in the uncued-blackout condition, and
      that the response requirement imposed by the fixed-interval schedules did not
      affect choice of the shorter delay, nor did the key-absent and key-present
      conditions. These results indicate that the keylight-stimulus conditions affected
      preference for the shorter of two delays and that the findings obtained in
      Experiment 1 depended mainly on the keylight-stimulus conditions of the terminal
      links (i.e., the conditioned reinforcing value of the terminal-link stimuli).

PMID- 16812691
TI  - Psychological distance to reward: Segmentation of aperiodic schedules of
      reinforcement.
AB  - College students responded for monetary rewards in two experiments on choice
      between differentially segmented aperiodic schedules of reinforcement. On a
      microcomputer, the concurrent chains were simulated as an air-defense video game
      in which subjects used two radars for detecting and destroying enemy aircraft. To
      earn more cash-exchangeable points, subjects had to shoot down as many planes as
      possible within a given period of time. For both experiments, access to one of
      two radar systems (terminal link) was controlled by a pair of independent
      concurrent variable-interval 60-s schedules (initial link) with a 4-s changeover
      delay always in effect. In Experiment 1, the appearance of an enemy aircraft in
      the terminal link was determined by a variable-interval (15 s or 60 s) schedule
      or a two-component chained variable-interval schedule of equal duration.
      Experiment 2 was similar to Experiment 1 except for the segmented schedule, which
      had three components. Subjects preferred the unsegmented schedule over its
      segmented counterpart in the conditions with variable-interval 60 s, and
      preference tended to be more pronounced with more components in the segmented
      schedule. These findings are compatible with those from previous studies of
      periodic and aperiodic schedules with pigeons or humans as subjects.

PMID- 16812692
TI  - To wait or to respond?
AB  - Emitting a certain response and waiting for a specified time without making that
      response had the same consequence. In Experiment 1, food-deprived pigeons were as
      likely to wait as to respond only if waiting provided food at a much higher
      frequency than did pecking. In Experiment 2, the consequence for humans was a
      brief light flash and tone. People were not biased for responding over waiting.
      Instead, their choices suggested crude payoff maximization. In Experiment 3,
      pigeons again obtained food, but they were not food deprived and could eat freely
      at each opportunity. Their behavior was more like that of the humans of
      Experiment 2 than that of food-deprived pigeons given small quantities of food at
      each feeding opportunity. The three experiments together showed that biases for
      responding over waiting were neither inherent characteristics of species nor
      inevitable outcomes of particular schedules. Choice between active search and
      waiting depended on ecological-motivational factors even when species and
      schedules were held constant.

PMID- 16812693
TI  - Pigeons' wait-time responses to transitions in interfood-interval duration:
      Another look at cyclic schedule performance.
AB  - Recent developments reveal that animals can rapidly learn about intervals of
      time. We studied the nature of this fast-acting process in two experiments. In
      Experiment 1 pigeons were exposed to a modified fixed-time schedule, in which the
      time between food rewards (interfood interval) changed at an unpredictable point
      in each session, either decreasing from 15 to 5 s (step-down) or increasing from
      15 to 45 s (step-up). The birds were able to track under both conditions by
      producing postreinforcement wait times proportional to the preceding interfood
      interval duration. However, the time course of responding differed: Tracking was
      apparently more gradual in the step-up condition. Experiment 2 studied the effect
      of having both kinds of transitions within the same session by exposing pigeons
      to a repeating (cyclic) sequence of the interfood-interval values used in
      Experiment 1. Pigeons detected changes in the input sequence of interfood
      intervals, but only for a few sessions-discrimination worsened with further
      training. The dynamic effects we observed do not support a linear waiting process
      of time discrimination, but instead point to a timing mechanism based on the
      frequency and recency of prior interfood intervals and not the preceding
      interfood interval alone.

PMID- 16812694
TI  - Editorial.

PMID- 16812695
TI  - Response deprivation, reinforcement, and economics.
AB  - Reinforcement of an instrumental response results not from a special kind of
      response consequence known as a reinforcer, but from a special kind of schedule
      known as a response-deprivation schedule. Under the requirements of a response
      deprivation schedule, the baseline rate of the instrumental response permits less
      than the baseline rate of the contingent response. Because reinforcement occurs
      only if the schedule deprives the organism of the contingent response,
      reinforcement cannot result from any intrinsic property of the contingent
      response or any property relative to the instrumental response. Two typical
      effects of response-deprivation schedules-facilitation of the instrumental
      response and suppression of the contingent response-are discussed in terms of
      economic concepts and models of instrumental performance. It is suggested that
      response deprivation makes the contingent response function as an economic good,
      the instrumental response as currency.

PMID- 16812696
TI  - The substitutability of reinforcers.
AB  - Substitutability is a construct borrowed from microeconomics that describes a
      continuum of possible interactions among the reinforcers in a given situation.
      Highly substitutable reinforcers, which occupy one end of the continuum, are
      readily traded for each other due to their functional similarity. Complementary
      reinforcers, at the other end of the continuum, tend to be consumed jointly in
      fairly rigid proportion, and therefore cannot be traded for one another except to
      achieve that proportion. At the center of the continuum are reinforcers that are
      independent with respect to each other; consumption of one has no influence on
      consumption of another. Psychological research and analyses in terms of
      substitutability employ standard operant conditioning paradigms in which humans
      and nonhumans choose between alternative reinforcers. The range of reinforcer
      interactions found in these studies is more readily accommodated and predicted
      when behavior-analytic models of choice consider issues of substitutability. New
      insights are gained into such areas as eating and drinking, electrical brain
      stimulation, temporal separation of choice alternatives, behavior therapy, drug
      use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains
      greater explanatory power and comprehensiveness when measures of substitutability
      are included.

PMID- 16812698
TI  - Adaptation, teleology, and selection by consequences.
AB  - This paper presents and defends the view that reinforcement and natural selection
      are selection processes, that selection processes are neither mechanistic nor
      teleological, and that mentalistic and vitalistic processes are teleological but
      not mechanistic. The differences between these types of processes are described
      and used in discussing the conceptual and methodological significance of
      "selection type theories" and B. F. Skinner's radical behaviorist view that
      "operant behavior is the field of intention, purpose, and expectation. It deals
      with that field precisely as the theory of evolution has dealt with another kind
      of purpose" (1986, p. 716). The antimentalism of radical behaviorism emerges as a
      post-Darwinian extension of Francis Bacon's (and Galileo's) influential view that
      "[the introduction of final causes] rather corrupts than advances the sciences"
      (Bacon, 1905, p. 302).

PMID- 16812697
TI  - Violations of transitivity: Implications for a theory of contextual choice.
AB  - Violations of strong stochastic transitivity in concurrent-chains choice were
      first reported by Navarick and Fantino. In a series of articles, Navarick and
      Fantino concluded that neither a unidimensional model capable of predicting exact
      choice probabilities nor a fixed-variable equivalence rule was possible for the
      concurrent-chains procedure. I show that when choice is modeled contextually
      (i.e., when preference for a schedule is affected by factors other than the
      schedule itself, e.g., aspects of the alternative schedule), a unidimensional,
      exact-choice probability model is possible that both predicts the
      intransitivities reported by Navarick and Fantino and provides a fixed-variable
      equivalence rule for the concurrent-chains procedure. The contextual model is an
      extension of the generalized matching law and violates a key assumption
      underlying traditional choice models-simple scalability-because of (a) schedule
      interdependence and (b) bias from procedural contingencies. Therefore, strong
      stochastic transitivity cannot be expected to hold. Contextual scalability is
      analyzed to reveal a hierarchy of context effects in choice. Navarick and
      Fantino's intransitivities can be satisfactorily explained by bias. If attribute
      sensitivity is context dependent, however, and if there are similarity structures
      among choice alternatives, the contextual model is shown to be able to predict
      violations of ordinal preference. Therefore, it may be possible to formulate a
      deterministic, general psychophysical model of choice as a behavioral alternative
      to probabilistic, multidimensional choice theories.

PMID- 16812699
TI  - The role of autoshaping in cooperative two-player games between starlings.
AB  - We report a study of the behavior of starlings in laboratory situations inspired
      by the "prisoner's dilemma." Our purpose is to investigate some possible
      mechanisms for the maintenance of cooperation by reciprocity and to investigate
      the process of autoshaping at a trial-by-trial level. In Experiment 1, pairs of
      starlings housed in adjacent cages played a discrete-trial "game" in which food
      could be obtained only by "cooperation." In this game, pecking at a response key
      eliminated the opportunity to obtain food but produced food for the partner. If
      neither bird pecked, neither had the opportunity to obtain food in that trial.
      Some level of cooperation persisted for several sessions whether the birds had
      been pretrained for a high or low probability of pecking at the key. The
      probability of a cooperative response was higher after trials in which the
      partner responded (and a reward was obtained) than after trials in which neither
      bird responded (and no reward was obtained), but the probability of a response
      was even higher after trials in which the same bird had responded, even though no
      reward was obtained by the actor in these trials. This behavior did not require
      visual presence of another player, because similar results were obtained in
      Experiment 2 (a replicate of Experiment 1 in which the members of the pair could
      not see each other) and in Experiment 3, a game in which each starling played
      with a computer responding with "tit for tat." Using an omission schedule, in
      which food was given in all trials in which the bird did not peck, Experiment 4
      showed that pecking could be maintained by autoshaping. In this experiment,
      overall probability of pecking decreased with experience, due to a drop in the
      tendency to peck in consecutive trials. The probability of pecking in trials
      following a reinforced trial did not decrease with experience. An implementation
      of the Rescorla-Wagner model for this situation was capable of reproducing molar,
      but not molecular, aspects of our results. The results violate the predictions of
      several game-theoretical models for the evolution of cooperation, including tit
      for tat, generous tit for tat, and the superior win-stay-lose-shift.

PMID- 16812700
TI  - Context specificity of operant discriminative performance in pigeons: II.
      Necessary and sufficient conditions.
AB  - Six experiments were performed to explore the necessary and sufficient conditions
      for producing context specificity of discriminative operant performance in
      pigeons. In Experiment 1, pigeons learned a successive discrimination (red
      S+/blue S-) in two chambers that had a particular odor present and between which
      they were frequently switched. The birds subsequently learned the reversal (blue
      S+/ red S-) in one of these chambers with a different odor present. When switched
      to the alternative chamber, although the odor and the reinforcement contingency
      were still appropriate to the reversal, performance appropriate to the original
      discrimination recurred in subjects for which the houselights were on during
      training and testing but not for those for which the houselights were off. This
      indicated the importance of visual contextual cues in producing context
      specificity. Experiment 2 showed that the frequent switching between boxes in
      initial training was of no consequence, presumably because the apparatus cues
      were highly salient to the subjects. Experiment 3 showed significantly less
      context specificity when odor cues were omitted. Experiment 4 showed that simply
      using a different reinforced stimulus in each phase of training was ineffective
      in producing context specificity. Experiment 5 showed that the generalization
      test procedure used in Experiment 4 was sensitive to context specificity when
      discrimination-reversal training was used with different odors in the two
      training phases. Experiment 6 replicated the results of Experiment 4, but then
      showed that when different odors accompanied the two training phases, context
      specificity was obtained with the single-stimulus paradigm. Thus in both single
      stimulus and discrimination-reversal paradigms, redundant odor cues potentiated
      learning about apparatus cues.

PMID- 16812701
TI  - Behavioral contrast for key pecking as a function of component duration when only
      one component varies.
AB  - Pigeons pecked keys for food reinforcers delivered by multiple variable-interval
      2-min variable-interval 2-min schedules. Positive behavioral contrast was created
      by changing one component to extinction; negative contrast was achieved by
      changing one component to a variable-interval 15-s schedule. The duration of each
      component was varied independently of the other from 5 to 960 s. The size of
      positive contrast was greatest when the extinction component was 30 or 60 s long.
      It did not change significantly with changes in the duration of the variable
      interval 2-min component. The absolute size of negative contrast decreased with
      increases in the duration of the variable-interval 2-min component. It did not
      change significantly with changes in the duration of the variable-interval 15-s
      component. These results show that the size of contrast is determined primarily
      by the duration of the component that provides the less favorable conditions of
      reinforcement. These results are not predicted by current theories.

PMID- 16812702
TI  - Bipolar control in fixed interfood intervals.
AB  - The ability of stimuli correlated with successive periods in a fixed interfood
      interval to support a response that produced or removed them was examined using
      pigeons. The degree to which those correlated stimuli elicited directed key pecks
      was also obtained. Stimuli early in the interval functioned as negative
      reinforcers, and stimuli late in the interval functioned as positive reinforcers.
      Stimuli correlated with successively later portions of the second half of the
      interval supported successively higher rates of elicited pecking and, with the
      exception of the final stimulus, supported successively higher rates of stimulus
      production. Stimuli in successively earlier portions of the first half of the
      interval supported successively higher rates of correlated-stimulus removal. This
      effect occurred in spite of the addition of a conjoint variable-interval
      dependency for food. An ogive fit to the mean normalized response distributions
      resulted in r(2)s demonstrating that most of the variance in the temporal
      organization of the behavior was accounted for. The findings were taken to
      indicate that fixed interfood intervals establish bipolar control.

PMID- 16812703
TI  - Stimulus control and response bias in an analogue prey-detection procedure.
AB  - The present study compared the performance of 6 pigeons trained to detect
      luminance differences in two different signal-detection procedures. Exposed to a
      three-key array, the pigeons were trained to peck the left key when the brighter
      of two light intensities had been presented on the center key and to peck the
      right key when the dimmer of two light intensities had been presented on the
      center key. Procedure A was a standard signal-detection procedure in which
      left/bright and right/dim responses produced food reinforcement and left/dim and
      right/bright responses produced periods of timeout. Procedure B was designed to
      simulate some of the contingencies operating in a prey-detection situation. Left
      key responses produced reinforcement following the brighter center-key stimulus
      and a period of timeout following the dimmer center-key stimulus. Right-key
      responses always produced a short period of timeout irrespective of the stimulus.
      Within each procedure, the duration of timeout arranged for false alarms
      (left/dim responses) was varied between 3 s and 120 s. Measures of accuracy and
      response bias were compared between the two procedures. The timeout manipulation
      produced systematic, but relatively small, changes in these measures when
      right/dim responses (i.e., correct rejections) produced reinforcement (Procedure
      A). Arranging timeout for right/dim responses in Procedure B produced greater
      variability in accuracy and response bias than did arranging reinforcement, but
      this variability was not related to timeout duration. Overall, discrimination
      accuracy was considerably higher when right/dim responses produced timeout than
      when they resulted in reinforcement, and accuracy was accompanied by a large bias
      toward the response associated with reinforcement. These results are consistent
      with a recently proposed model of signal detection.

PMID- 16812705
TI  - Quickening the pace of our discussions (Editorial).

PMID- 16812706
TI  - The conventional wisdom of behavior analysis.

PMID- 16812704
TI  - Momentary maximizing in concurrent schedules with a minimum interchangeover
      interval.
AB  - Eight pigeons were trained on concurrent variable-interval variable-interval
      schedules with a minimum interchangeover time programmed as a consequence of
      changeovers. In Experiment 1 the reinforcement schedules remained constant while
      the minimum interchangeover time varied from 0 to 200 s. Relative response rates
      and relative time deviated from relative reinforcement rates toward indifference
      with long minimum interchangeover times. In Experiment 2 different reinforcement
      ratios were scheduled in successive experimental conditions with the minimum
      interchangeover time constant at 0, 2, 10, or 120 s. The exponent of the
      generalized matching equation was close to 1.0 when the minimum interchangeover
      time was 0 s (the typical procedure for concurrent schedules without a changeover
      delay) and decreased as that duration was increased. The data support the
      momentary maximizing theory and contradict molar maximizing theories and the
      melioration theory.

PMID- 16812707
TI  - The unconventional philosophy of science of behavior analysis.

PMID- 16812708
TI  - The unconventional wisdom of B. F. Skinner: The analysis-interpretation
      distinction.

PMID- 16812710
TI  - Why environmentally based analyses are necessary in behavior analysis.

PMID- 16812709
TI  - Commonsense and conventional wisdom.

PMID- 16812711
TI  - A body must have flesh and bones.

PMID- 16812712
TI  - Internal states: Necessary but not sufficient.

PMID- 16812713
TI  - Macht's nicht? A commentary on Staddon's "The conventional wisdom of behavior
      analysis".

PMID- 16812714
TI  - On the ratification of states: A response to Staddon.

PMID- 16812715
TI  - Observation and theory in behavior analysis.

PMID- 16812716
TI  - Boring's Mach and state variables.

PMID- 16812717
TI  - The conventional wisdom of behavior analysis: Response to comments.

PMID- 16812718
TI  - Compound stimuli in emergent stimulus relations: Extending the scope of stimulus
      equivalence.
AB  - Three experiments were conducted to investigate stimulus relations that might
      emerge when college students are taught relations between compound sample stimuli
      and unitary comparison stimuli using match-to-sample procedures. In Experiment 1,
      subjects were taught nine AB-C stimulus relations, then tested for the emergence
      of 18 AC-B and BC-A relations. All subjects showed the emergence of all tested
      relations. Twelve subjects participated in Experiment 2. Six subjects were taught
      nine AB-C relations and were then tested for symmetrical (C-AB) relations. Six
      subjects were taught nine AB-C and three C-D relations and were then tested for
      nine AB-D (transitive) relations. Five of 6 subjects demonstrated the emergence
      of symmetrical relations, and 6 subjects showed the emergence of transitivity. In
      Experiment 3, 5 college students were taught nine AB-C and three C-D relations
      and were then tested for nine equivalence (D-AB) relations and 18 AD-B and BD-A
      relations. Three subjects demonstrated all tested relations. One subject
      demonstrated the AD-B and BD-A relations but not the D-AB relations. One subject
      did not respond systematically during testing. The results of these experiments
      extend stimulus equivalence research to more complex cases.

PMID- 16812719
TI  - Session duration and the VI response function: Within-session prospective and
      retrospective effects.
AB  - Two experiments examined the effects of session duration on responding during
      simple variable-interval schedules. In Experiment 1, rats were exposed to a
      series of simple variable-interval schedules differing in both session duration
      (10 min or 30 min) and scheduled reinforcement rate (7.5 s, 15 s, 30 s, and 480
      s). The functions relating response rate to reinforcement rate were predominantly
      monotonic for the short (10-min) sessions but were predominantly bitonic for the
      long (30-min) sessions, when data from the entire session were considered.
      Examination of responding within sessions suggested that differences in the whole
      session data were produced by a combination of prospective processes (i.e.,
      processes based on events scheduled to occur later in the session) and
      retrospective processes (i.e., processes based on events that had already
      occurred in the session). In Experiment 2, rats were exposed to a modified
      discrimination procedure in which pellet flavor (standard or banana) predicted
      session duration (10 min or 30 min). All rats came to respond faster during the
      short (10-min) sessions than during the first 10 min of the long sessions. As in
      Experiment 1, the results seemed to reflect the simultaneous operation of both
      prospective and retrospective processes. The results shed light on the recent
      controversy over the form of the variable-interval response function by
      identifying one variable (session duration) and two types of processes
      (prospective and retrospective) that influence responding on these schedules.

PMID- 16812720
TI  - Temporal control in fixed-interval schedules.
AB  - The peak procedure was used to study temporal control in pigeons exposed to seven
      fixed-interval schedules ranging from 7.5 to 480 s. The focus was on behavior in
      individual intervals. Quantitative properties of temporal control depended on
      whether the aspect of behavior considered was initial pause duration, the point
      of maximum acceleration in responding, the point of maximum deceleration, the
      point at which responding stopped, or several different statistical derivations
      of a point of maximum responding. Each aspect produced different conclusions
      about the nature of temporal control, and none conformed to what was known
      previously about the way ongoing responding was controlled by time under
      conditions of differential reinforcement. Existing theory does not explain why
      Weber's law so rarely fit the results or why each type of behavior seemed unique.
      These data fit with others suggesting that principles of temporal control may
      depend on the role played by the particular aspect of behavior in particular
      situations.

PMID- 16812721
TI  - Shortcomings of the behavioral competition theory of contrast: Reanalysis of
      McLean (1992).
AB  - McLean (1992) presented significant data showing that the occurrence of
      behavioral contrast in a multiple schedule was correlated with shifts in the
      frequency of reinforcers from a second source between components of the schedule,
      and interpreted his results as showing that contrast was due to changes in the
      degree of response competition within the constant component of the multiple
      schedule. Reanalysis of his data shows that there was an effect of reinforcement
      in the alternative component of the schedule independent of the shifts in
      reinforcers between components. Thus, the effect of relative rate of
      reinforcement cannot be ascribed, at least entirely, to the mechanisms proposed
      by the behavioral competition theory of contrast.

PMID- 16812722
TI  - A contextual model of concurrent-chains choice.
AB  - An extension of the generalized matching law incorporating context effects on
      terminal-link sensitivity is proposed as a quantitative model of behavior under
      concurrent chains. The contextual choice model makes many of the same qualitative
      predictions as the delay-reduction hypothesis, and assumes that the crucial
      contextual variable in concurrent chains is the ratio of average times spent, per
      reinforcement, in the terminal and initial links; this ratio controls
      differential effectiveness of terminal-link stimuli as conditioned reinforcers.
      Ninety-two concurrent-chains data sets from 19 published studies were fitted to
      the model. Averaged across all studies, the model accounted for 90% of the
      variance in pigeons' relative initial-link responding. The model therefore
      demonstrates that a matching law analysis of concurrent chains-the assumption
      that relative initial-link responding equals relative terminal-link value-remains
      quantitatively viable. Because the model reduces to the generalized matching law
      when terminal-link duration is zero, it provides a quantitative integration of
      concurrent schedules and concurrent chains.

PMID- 16812723
TI  - The behavioral theory of timing: Reinforcer rate determines pacemaker rate.
AB  - In the behavioral theory of timing, pulses from a hypothetical Poisson pacemaker
      produce transitions between states that are correlated with adjunctive behavior.
      The adjunctive behavior serves as a discriminative stimulus for temporal
      discriminations. The present experiments tested the assumption that the average
      interpulse time of the pacemaker is proportional to interreinforcer interval.
      Responses on a left key were reinforced at variable intervals for the first 25 s
      since the beginning of a 50-s trial, and right-key responses were reinforced at
      variable intervals during the second 25 s. Psychometric functions relating
      proportion of right-key responses to time since trial onset, in 5-s intervals
      across the 50-s trial, were sigmoidal in form. Average interpulse times derived
      by fitting quantitative predictions from the behavioral theory of timing to
      obtained psychometric functions decreased when the interreinforcer interval was
      decreased and increased when the interreinforcer interval was increased, as
      predicted by the theory. In a second experiment, average interpulse times
      estimated from trials without reinforcement followed global changes in
      interreinforcer interval, as predicted by the theory. Changes in temporal
      discrimination as a function of interreinforcer interval were therefore not
      influenced by the discrimination of reinforcer occurrence. The present data
      support the assumption of the behavioral theory of timing that interpulse time is
      determined by interreinforcer interval.

PMID- 16812724
TI  - Response acquisition by Siamese fighting fish (Betta splendens) with delayed
      visual reinforcement.
AB  - Male Siamese fighting fish, Betta splendens, swam through a ring in an aquarium,
      breaking a photocell beam and initiating an unsignaled, resetting delay interval.
      Following delays of 0 s, 10 s, or 25 s, a 15-s mirror presentation released an
      aggressive display by the fish. Swimming through the ring increased in the
      absence of either a period of acclimatization to the reinforcer (analogous to
      magazine training when appetitive reinforcers are used) or explicit training of
      the response by the experimenters. Response rates were a decreasing function of
      delay duration. Other fish exposed to a schedule of response-independent mirror
      presentations failed to acquire and maintain the response. The results
      demonstrate the robustness and generality of the phenomenon of response
      acquisition with delayed reinforcement. They further qualify earlier observations
      about behavioral mechanisms involved in the phenomenon.

PMID- 16812725
TI  - Effects of the discriminability of alternatives in three-alternative concurrent
      schedule performance.
AB  - Six pigeons were trained on two- and three-alternative concurrent schedules in
      which the alternatives were signaled by different wavelengths of light on the
      main pecking key. The schedules were arranged according to a switching-key
      procedure in which pecks on a white side key produced a 3-s blackout and,
      intermittently, a change in the variable-interval schedule of food programmed on
      the main (center) key after the blackout. In Part 1, a two-alternative concurrent
      variable-interval schedule was arranged in which the alternatives were signaled
      by 560 nm and 630 nm. Parts 2 and 3 arranged three-alternative concurrent
      variable-interval schedules with the alternatives signaled by 560 nm, 600 nm, and
      630 nm (Part 2) and 560 nm, 623 nm, and 630 nm (Part 3). Within each part, the
      relative rate of food reinforcers available on the alternatives was varied across
      a wide range. In all parts of the experiment, the ratios of responses emitted
      between pairs of alternatives were more extreme than the ratios of reinforcers
      obtained on the pairs of alternatives, a result termed overmatching. In Parts 2
      and 3, generalized matching sensitivities between pairs of alternatives were
      found to be higher when the reinforcer rate on the third alternative was low than
      when it was high-an apparent failure of the constant-ratio rule. The data were
      well described by an extension of the Davison and Jenkins (1985) model, which
      assumes differing discriminabilities between concurrent-schedule alternatives in
      combination with a punishing effect of blackout following changeovers.

PMID- 16812726
TI  - A festschrift in honor of Joseph V. Brady in his 70th year.

PMID- 16812727
TI  - Designing a behavioral program for a barrio in Tegucigalpa, Honduras.
AB  - Health in Housing initiated a behavioral program of education and skills training
      for children and adults in a community of 30,000 persons living in substandard
      conditions in Tegucigalpa, Honduras. To measure achievement in the long-range
      project, 21 families of Flor del Campo participated in a preliminary three-part
      survey of their (a) health, (b) housing and the environment, and (c) family
      history. Doctors, designers, and educators worked with Honduran personnel in the
      first survey. Following functional analyses of the home and surrounding
      environment and the physical status of the individuals living there, procedures
      provide the family with treatment and training for home and environment
      improvement. Graphic, verbal, and numerical data, incorporated into a master
      computerized system, record events of each family member: training programs
      experienced, health care delivery courses taken, medical treatments, growth of
      children, literacy changes, educational courses completed, kinds and amounts of
      foods eaten, household and building materials purchased. Ongoing functional
      analysis and a long-range evaluation are made of the progress of each
      participating individual in a family. Teams revisit each house to observe and
      record any changes in the physical and environmental facility and the health and
      life-styles, and to report any indications of new health problems or recurrences.

PMID- 16812728
TI  - An investigation of the differential-outcomes effect within sessions.
AB  - The differential-outcomes effect is manifest as more accurate performance of a
      delayed conditional discrimination when alternative choice responses are followed
      by different reinforcers than when they are followed by the same reinforcer. In
      Experiment 1, a differential-outcomes effect was demonstrated within sessions by
      signaling the duration of food access for correct responses with stimuli
      appearing in conjunction with the sample stimuli. The delayed matching-to-sample
      performance of 5 pigeons was more accurate when green choice responses (matching
      a green sample) were followed by 3.5-s food access and red choice responses
      (matching a red sample) were followed by 0.5-s food access (different-outcome
      trials) than when the correct choice responses were both followed by 1.5-s
      reinforcers (same-outcome trials). In Experiment 2, the acquisition of this
      differential-outcomes effect was characterized by a progressive decrease in rate
      of forgetting on different-outcome trials and no change in rate of forgetting on
      same-outcome trials. In addition, accuracy at the shortest delay intervals for
      both different-outcome and same-outcome trials increased over acquisition, but to
      a greater extent for different-outcome trials. These data suggest that both
      memorial and attentional (time-dependent and time-independent) factors contribute
      to the differential-outcomes effect.

PMID- 16812729
TI  - Contrast and undermatching with regular or irregular alternation of components.
AB  - Behavioral contrast and response-ratio sensitivity to reinforcement were compared
      in multiple schedules in which components alternated strictly or according to a
      pseudorandom sequence. Average component durations in the two regimes were always
      60 s, and order of presentation of component alternation regimes was
      counterbalanced across subjects. In Part 1, the reinforcer rate in one component
      was reduced from 60 per hour to zero, while that in the other component was
      unchanged. Positive behavioral contrast occurred in the constant component in
      that response rates increased, but neither the reliability nor the magnitude of
      contrast was affected by the manner in which components alternated. Part 2 was
      similar, except that a number of different reinforcer rates were used in the
      varied component. Neither contrast nor sensitivity of response ratios to changes
      in reinforcer ratios depended on the regime of component alternation. Thus, the
      predictability in time of future reinforcement conditions, which is a feature of
      regular multiple scheduling, does not appear to be a determinant of multiple
      schedule performance.

PMID- 16812730
TI  - Brief-stimulus presentations on multiform tandem schedules.
AB  - Three experiments examined the influence of a brief stimulus (a light) on the
      behavior of food-deprived rats whose lever pressing on tandem schedules
      comprising components of different schedule types resulted in food presentation.
      In Experiment 1, either a tandem variable-ratio variable-interval or a tandem
      variable-interval variable-ratio schedule was used. The variable-interval
      requirement in the tandem variable-ratio variable-interval schedule was yoked to
      the time taken to complete the variable-ratio component in the tandem variable
      interval variable-ratio schedule, and the length of the variable-interval
      component in the latter schedule was yoked to the variable-ratio component in the
      former schedule. If a brief stimulus occurred following completion of the first
      component, then behavior was differentiated in the two components; subjects
      responded more quickly in the variable-ratio than in the variable-interval
      component. If the stimulus was removed, then response rate was determined by the
      nature of the final component. Similar results were obtained in Experiments 2 and
      3 with the use of a three-component tandem variable-ratio variable-interval
      variable-ratio schedule or tandem variable-interval variable-ratio variable
      interval schedule. Thus, a brief stimulus that was not explicitly paired with
      reinforcement engendered behavior typical of the component schedule preceding its
      presentation.

PMID- 16812731
TI  - Precurrent contingencies: Behavior reinforced by altering reinforcement
      probability for other behavior.
AB  - The present study explored the effects of a precurrent contingency in which one
      (precurrent) activity increased the reinforcement probability for another
      (current) activity. Four human subjects responded on a two-key computer mouse.
      Each right-key press was reinforced (points exchangeable for money) with .02
      probability. In one condition (no precurrent contingency), pressing the left key
      had no scheduled consequence; in another condition (precurrent contingency),
      pressing the left key increased the reinforcement probability for right-key
      responding to .08 for 15 s. Initial exposure to the precurrent contingency
      resulted in acquisition of precurrent left-key responding for 3 subjects, but for
      the 4th subject a special contingency was required. Right-key responding occurred
      at a high stable rate across the conditions. Changeovers to left-key responding
      dropped to near zero when the precurrent contingency was absent and were
      maintained at enhanced levels when the precurrent contingency was present.
      Contacts with the left key consisted of short response runs. Right-key responses
      were more frequently emitted within 15 s of a left-key response when the
      precurrent contingency was present, an efficient adaptation to the contingency.
      Continued research on precurrent behavior may produce insights into complex
      phenomena such as autoclitics and self-control.

PMID- 16812732
TI  - Response-rate differences in variable-interval and variable-ratio schedules: An
      old problem revisited.
AB  - In Experiment 1, a variable-ratio 10 schedule became, successively, a variable
      interval schedule with only the minimum interreinforcement intervals yoked to the
      variable ratio, or a variable-interval schedule with both interreinforcement
      intervals and reinforced interresponse times yoked to the variable ratio.
      Response rates in the variable-interval schedule with both interreinforcement
      interval and reinforced interresponse time yoking fell between the higher rates
      maintained by the variable-ratio schedule and the lower rates maintained by the
      variable-interval schedule with only interreinforcement interval yoking. In
      Experiment 2, a tandem variable-interval 15-s variable-ratio 5 schedule became a
      yoked tandem variable-ratio 5 variable-interval x-s schedule, and a tandem
      variable-interval 30-s variable-ratio 10 schedule became a yoked tandem variable
      ratio 10 variable-interval x-s schedule. In the yoked tandem schedules, the
      minimum interreinforcement intervals in the variable-interval components were
      those that equated overall interreinforcement times in the two phases. Response
      rates did not decline in the yoked schedules even when the reinforced
      interresponse times became longer. Experiment 1 suggests that both reinforced
      interresponse times and response rate-reinforcement rate correlations determine
      response-rate differences in variable-ratio 10 and yoked variable-interval
      schedules in rats. Experiment 2 suggests a minimal role for the reinforced
      interresponse time in determining response rates on tandem variable-interval 30-s
      variable-ratio 10 and yoked tandem variable-ratio 10 variable-interval x-s
      schedules in rats.

PMID- 16812733
TI  - Reinforcer magnitude (sucrose concentration) and the matching law theory of
      response strength.
AB  - This experiment investigated the relationship between reinforcer magnitude
      (sucrose concentration) and response rate. The purpose was to evaluate the
      behavior of two parameters of an equation that predicts absolute response rate as
      a function of reinforcement rate and two free parameters. According to
      Herrnstein's (1970) theory of reinforced behavior, one parameter of this
      "response-strength equation" measures the efficacy of the reinforcer maintaining
      responding and the other parameter measures motoric components of response rate,
      such as response duration. Seven rats served as subjects. Experimental sessions
      consisted of a series of five different variable-interval schedules of
      reinforcement, each in effect for 5 minutes. Within each session, obtained
      reinforcement rates varied over more than a 30-fold range, from about 20 per hour
      to 700 per hour. The reinforcer was sucrose solution, and, between sessions, its
      concentration was varied from 0.0 to 0.64 molar (0 to 21.9%). For sucrose
      concentrations of 0.16 to 0.64 m, response rate was a negatively accelerated
      function of reinforcement rate. Increases in sucrose concentration increased
      response rates maintained by low but not high reinforcement rates. This pattern
      of changes corresponds to a change in the reinforcement-efficacy parameter of the
      response-strength equation. In contrast, the motor-performance parameter did not
      change as a function of sucrose concentration. These findings are inconsistent
      with the results of a similar study (Bradshaw, Szabadi, & Bevan, 1978) but
      support Herrnstein's theory of reinforced behavior.

PMID- 16812734
TI  - Basic research needed for stimulating the development of behavioral technologies.
AB  - The costs of disconnection between the basic and applied sectors of behavior
      analysis are reviewed, and some solutions to these problems are proposed. Central
      to these solutions are collaborations between basic and applied behavioral
      scientists in programmatic research that addresses the behavioral basis and
      solution of human behavior problems. This kind of collaboration parallels the
      deliberate interactions between basic and applied researchers that have proven to
      be so profitable in other scientific fields, such as medicine. Basic research
      questions of particular relevance to the development of behavioral technologies
      are posed in the following areas: response allocation, resistance to change,
      countercontrol, formation and differentiation/discrimination of stimulus and
      response classes, analysis of low-rate behavior, and rule-governed behavior.
      Three interrelated strategies to build connections between the basic and applied
      analysis of behavior are identified: (a) the development of nonhuman animal
      models of human behavior problems using operations that parallel plausible human
      circumstances, (b) replication of the modeled relations with human subjects in
      the operant laboratory, and (c) tests of the generality of the model with actual
      human problems in natural settings.

PMID- 16812735
TI  - Temporal discrimination learning of operant feeding in goldfish (Carassius
      auratus).
AB  - Operant temporal discrimination learning was investigated in goldfish. In the
      first experiment, there was a fixed daily change in illumination. Eight subjects
      were trained to operate a lever that reinforced each press with food. The period
      during which responses were reinforced was then progressively reduced until it
      was 1 hr in every 24. The final 1-hr feeding schedule was maintained over 4
      weeks. The feeding period commenced at the same time each day throughout. The
      food dispensers were then made inactive, and a period of extinction ensued for 6
      days. The pattern of responding suggested that the fish were able to exhibit
      temporal discrimination in anticipation of feeding time. This pattern of
      responding persisted for a limited number of days during the extinction
      procedure. The second experiment produced evidence that operant temporal
      discrimination could develop under continuous illumination.

PMID- 16812736
TI  - Within-session changes in responding during several simple schedules.
AB  - Pigeons' key pecking was reinforced by food delivered by several fixed-interval,
      variable-ratio, and differential-reinforcement-of-low-rate schedules. Rate of
      responding, number of responses per reinforcer, length of postreinforcement
      pause, running response rate, and the time required to collect an available
      reinforcer changed systematically within sessions when the schedules provided
      high rates of reinforcement, but usually not when they provided low rates. These
      results suggest that the factors that produce within-session changes in
      responding are generally similar for different schedules of reinforcement.
      However, a separate factor may also contribute during variable-ratio schedules.
      The results question explanations for within-session changes that are related
      solely to the passage of time, to responding, and to one interpretation of
      attention. They support the idea that one or more factors related to
      reinforcement play a role.

PMID- 16812737
TI  - The effect of variable delays on self-control.
AB  - Five pigeons served as subjects in an experiment that examined the effects of
      variable as opposed to fixed delays on preference in a self-control paradigm
      (choice between larger, more delayed and smaller, less delayed reinforcers).
      Nonindependent concurrent variable-interval schedules were used to measure
      choice. When delays to the larger, more delayed reinforcers were variable as
      opposed to fixed, the subjects showed an increased preference for that
      alternative (the self-control alternative). A series of regressions revealed that
      the hyperbolic decay model and incentive theory provided poor fits to the data,
      but a modified version of the generalized matching law provided an adequate fit.
      Together, consistent with a general prediction made by discounting models, the
      data supported the conclusion that variable delays can increase self-control.
      However, specific discounting models were not able to explain the present data
      well.

PMID- 16812738
TI  - Leaving patches: An investigation of a laboratory analogue.
AB  - Five pigeons were trained on a procedure that has been used as a laboratory
      analogue to natural patch residence. Trials commenced with two responses
      available. One of these might provide a reinforcer if the patch was a prey patch;
      the other ended the residence time in the patch and, after a fixed travel time in
      blackout, produced another patch that might or might not provide a reinforcer.
      Patch residence also ended, and was followed by the same travel time, after a
      reinforcer was obtained or after a fixed maximum time was spent in the patch. The
      dependent variable was patch residence time, from the commencement of the patch
      to the time at which the subject emitted a response to exit from the patch or
      until the maximum patch residence time had elapsed. In Parts 1 to 3, the duration
      of the imposed travel time was varied from 0.25 to 16 s at three different
      probabilities (.05, .1, and .2) of food per second (lambda) in prey patches. As
      reported in previous research, both increasing travel time and decreasing
      probabilities of reinforcers per second increased patch residence time. In Parts
      4 to 7, the probability of prey trials (rho) was varied in an irregular order
      from .1, through .2, .5, and .7, to .9 for different combinations of lambda and
      travel time. Respectively, these were in Part 4, .05 per second and 0.25 s; in
      Part 5, .05 per second and 16 s; in Part 6, .2 per second and 0.25 s; and in Part
      7, .2 per second and 16 s. A previously offered model, based on optimization
      assumptions, substantially and consistently underpredicted patch residence time.
      However, a modification of that model, which assumes that the subjects could not
      accurately discriminate the residence time that provided the minimum
      interreinforcer interval, described the data well. The same model also described
      previously reported residence times in a different species with a uniform
      distribution of prey-arrival times.

PMID- 16812739
TI  - Context specificity of conditioned-reinforcement effects on discrimination
      acquisition.
AB  - Pigeons were trained on a series of reversals of a simultaneous form
      discrimination in which the trial outcomes were separated from the choice
      responses by an 8-s delay interval. Different conditions were defined by the
      stimuli occurring during the two halves of the delay interval. Discrimination
      learning was greatly facilitated by having differential stimuli during the delay
      following correct versus incorrect choices. When the differential stimuli
      appeared only at the midpoint of the delay, some facilitation occurred relative
      to when no different stimuli occurred, but there was substantially less
      facilitation than when the differential stimuli occurred immediately contingent
      on choice. A reversed-stimulus condition, in which the stimulus at the onset of
      the delay following a correct choice was the same as that during the last segment
      of the delay following an incorrect choice, and the stimulus at the onset of the
      delay following an incorrect choice was the same as that preceding food during
      the last segment of the delay following a correct choice, also facilitated
      discrimination learning relative to the nondifferential stimulus conditions.

PMID- 16812740
TI  - Leaving patches: Effects of travel requirements.
AB  - Five pigeons were trained in an analogue foraging procedure in which, by
      completing a travel requirement, they entered a "patch" in which a reinforcer
      might be available after an unpredictable time. They also had the opportunity, by
      emitting a defined response, to exit the patch and travel to another patch. Prey
      availability in a patch was not signaled. Data were collected on the length of
      time that subjects stayed in patches before exiting (residence times) as a
      function of various travel requirements: travel for a fixed time in blackout,
      fixed-interval schedule traveling, fixed-time traveling with an added response
      required to terminate traveling, and fixed-ratio traveling. For each of these
      conditions, the required amount of travel (time or responses) was varied over a
      wide range. As previously reported, residence times increased with increases in
      fixed-time traveling, as they did with increasing fixed-interval or fixed-ratio
      traveling. There was no evidence that adding response or work requirements
      systematically affected residence time except via increased travel time, although
      3 of the 5 birds stayed longer in a patch under higher fixed-ratio values. A
      "threshold-maximization" model described the data well with a single parameter
      that was consistent across subjects, procedures, and experiments.

PMID- 16812741
TI  - Bias in self-evaluation: Signal probability effects.
AB  - Two experiments examined apparent signal probability effects in simple verbal
      self-reports. After each trial of a delayed matching-to-sample task, young adults
      pressed either a "yes" or a "no" button to answer a computer-presented query
      about whether the most recent choice met a point contingency requiring both speed
      and accuracy. A successful matching-to-sample choice served as the "signal" in a
      signal-detection analysis of self-reports. Difficulty of matching to sample, and
      thus signal probability, was manipulated via the number of nonmatching sample and
      comparison stimuli. In Experiment 1, subjects exhibited a bias (log b) for
      reporting matching-to-sample success when success was frequent, and no bias or a
      bias for reporting failure when success was infrequent. Contingencies involving
      equal conditional probabilities of point consequences for "I succeeded" and "I
      failed" reports had no systematic effect on this pattern. Experiment 2 found
      signal probability effects to be evident regardless of whether referent-response
      difficulty was manipulated in different conditions or within sessions. These
      findings indicate that apparent signal probability effects in self-report bias
      that were observed in previous studies probably were not an artifact of
      contingencies intended to improve self-report accuracy or of the means of
      manipulating signal probability. The findings support an analogy between simple
      self-reports and psychophysical judgments and bolster the conclusion of
      Critchfield (1993) that signal probability effects can influence simple self
      reports much as they do reports about external stimuli in psychophysical
      experiments.

PMID- 16812742
TI  - A transfer of self-discrimination response functions through equivalence
      relations.
AB  - The present study tested the idea that human self-discrimination response
      functions may transfer through equivalence relations. Four subjects were trained
      in six symbolic matching-to-sample tasks (if see A1, choose B1; A1-C1, A2-B2, A2
      C2, A3-B3, A3-C3) and were then tested for the formation of three equivalence
      relations (B1-C1, B2-C2, B3-C3). Two of the B stimuli (B1 and B2) were then used
      to train two different self-discrimination responses using either detailed
      instructions (Subjects 1 to 3) or minimal instructions (Subject 4) on two complex
      schedules of reinforcement (i.e., subjects were trained to pick the B1 stimulus
      if they had not emitted a response, and to pick the B2 stimulus if they had
      emitted one or more responses on the previous schedule). All 4 subjects showed
      the predicted transfer of self-discrimination response functions through
      equivalence relations (i.e., no response on the schedule, pick C1; one or more
      responses on the schedule, pick C2). Subjects also demonstrated this transfer
      when they were required to discriminate their schedule performance before
      exposure to the schedule (i.e., "what I intend to do"). Four control subjects
      were also used in the study. Two of these (Subjects 5 and 6) were not exposed to
      any form of matching-to-sample training and testing (nonequivalence controls).
      The 2 remaining subjects (7 and 8) were exposed to matching-to-sample training
      and testing that incorporated stimuli not used during the transfer test; C1 and
      C2 were replaced by N1 and N2 during the matching-to-sample training and testing,
      but C1 and C2 were used for the transfer tests (equivalence controls). All 4
      subjects failed to produce the self-discrimination transfer performances observed
      with the experimental subjects.

PMID- 16812744
TI  - Social history and the behavioral repertoire.

PMID- 16812743
TI  - Effects of different accessibility of reinforcement schedules on choice in
      humans.
AB  - Based on the delay-reduction hypothesis, a less profitable schedule should be
      rejected if its duration exceeds the mean delay to reinforcement. It should be
      accepted if its duration is shorter than the mean delay. This was tested for
      humans, using a successive-choice schedule. The accessibility of the less
      profitable (variable-interval 18 s) schedule was varied by changing the duration
      (in terms of a fixed interval) of the waiting-time component preceding its
      presentation. Forty-eight students were randomly assigned to three groups. In
      Phase 1, the duration of the less profitable schedule equaled the mean delay to
      reinforcement in all groups. In Phase 2, waiting time preceding the less
      profitable schedule was reduced in Group 1 and increased in Group 2. Thus, the
      schedule was correlated either with a relative delay increase (Group 1) or a
      delay reduction (Group 2). In Group 3, conditions remained unchanged. As
      predicted, acceptance of the less profitable schedule decreased in Group 1 and
      increased in Group 2. The increased acceptance in Group 2 was accompanied by a
      decreased acceptance of the more profitable (variable-interval 3 s) schedule,
      resembling a pattern of negative contrast. Response rates were higher under the
      component preceding (a) the more profitable schedule in Group 1 and (b) the less
      profitable schedule in Group 2. Implications for the modification of human choice
      behavior are discussed.

PMID- 16812746
TI  - Choice between reliable and unreliable reinforcement alternatives revisited:
      Preference for unreliable reinforcement.
AB  - Pigeons' choices between a reliable alternative that always provided food after a
      delay (i.e., 100% reinforcement) and an unreliable one that provided food or
      blackout equally often after a delay (i.e., 50% reinforcement) was studied using
      a discrete-trials concurrent-chains procedure modified to prevent choice between
      alternatives following a blackout outcome. Initial links were fixed-ratio 1
      schedules, and terminal links were fixed-time schedules. Stimuli presented during
      the terminal-link delays were correlated with the food and blackout outcomes. In
      Experiment 1, terminal-link durations were varied. With short terminal links
      (i.e., 10 s), 6 of 8 subjects showed strong preference for the 50% side. As
      terminal-link duration increased to 30 s, preference, regardless of direction,
      became less extreme. In Experiment 2, the side-key location of the 50% and 100%
      alternatives was reversed for 3 subjects. Preference for the 50% alternative
      reoccurred following the key reversal. When a 5-s separation was subsequently
      interposed between the initial and terminal links for both alternatives, all
      birds reversed to a preference for the 100% side. In general, the strong
      preference for the 50% side was qualitatively consistent with the expectation
      that the procedure enhanced the conditioned-reinforcement effectiveness of the
      food-associated terminal-link stimulus on the 50% side. Implications of the
      results for various accounts of choice of the 50% alternative are discussed.

PMID- 16812745
TI  - The transfer of respondent eliciting and extinction functions through stimulus
      equivalence classes.
AB  - Two studies investigated the transfer of respondent elicitation through
      equivalence classes. In Experiment 1, match-to-sample procedures were used to
      teach 8 subjects two four-member equivalence classes. One member of one class was
      then paired with electric shock, and one member of the other class was presented
      without shock. All remaining stimuli were then presented. Using skin conductance
      as the measure of conditioning, transfer of conditioning was demonstrated in 6 of
      the 8 subjects. In Experiment 2, similar procedures were used to replicate the
      results of Experiment 1 and investigate the transfer of extinction. Following
      equivalence training and conditioning to all members of one class, one member was
      then presented in extinction. When the remaining stimuli from this class were
      then presented, they failed to elicit skin conductance. In the final phase of the
      experiment, the stimulus that was previously presented in extinction was
      reconditioned. Test trials with other members of the class revealed that they
      regained elicitation function. These results demonstrate that both respondent
      elicitation and extinction can transfer through stimulus classes. The clinical
      and applied significance of the results is discussed.

PMID- 16812747
TI  - Instructional versus schedule control of humans' choices in situations of
      diminishing returns.
AB  - Four adult humans chose repeatedly between a fixed-time schedule (of points later
      exchangeable for money) and a progressive-time schedule that began at 0 s and
      increased by a fixed number of seconds with each point delivered by that
      schedule. Each point delivered by the fixed-time schedule reset the requirements
      of the progressive-time schedule to its minimum value. Subjects were provided
      with instructions that specified a particular sequence of choices. Under the
      initial conditions, the instructions accurately specified the optimal choice
      sequence. Thus, control by instructions and optimal control by the programmed
      contingencies both supported the same performance. To distinguish the effects of
      instructions from schedule sensitivity, the correspondence between the instructed
      and optimal choice patterns was gradually altered across conditions by varying
      the step size of the progressive-time schedule while maintaining the same
      instructions. Step size was manipulated, typically in 1-s units, first in an
      ascending and then in a descending sequence of conditions. Instructions quickly
      established control in all 4 subjects but, by narrowing the range of choice
      patterns, they reduced subsequent sensitivity to schedule changes. Instructional
      control was maintained across the ascending sequence of progressive-time values
      for each subject, but eventually diminished, giving way to more schedule
      appropriate patterns. The transition from instruction-appropriate to schedule
      appropriate behavior was characterized by an increase in the variability of
      choice patterns and local increases in point density. On the descending sequence
      of progressive-time values, behavior appeared to be schedule sensitive, sometimes
      even optimally sensitive, but it did not always change systematically with the
      contingencies, suggesting the involvement of other factors.

PMID- 16812748
TI  - Cued and uncued terminal links in concurrent-chains schedules.
AB  - Pigeons were trained on a concurrent-chains schedule. The initial links were
      concurrent variable-interval schedules arranged on two side keys. Each terminal
      link was a fixed-interval schedule arranged on the center key. In cued
      conditions, different center-key colors signaled the two terminal-link schedules.
      In uncued conditions, the same center-key color appeared for both terminal links.
      Experiment 1 arranged unequal initial links and equal terminal links. Preference
      for the shorter initial-link schedule was greater when the terminal links were
      uncued. Experiment 2 arranged equal initial links and unequal terminal links.
      Preference for the shorter terminal-link schedule was greater when the terminal
      links were cued. Although the results of Experiment 2 successfully replicated
      previous research, the results of Experiment 1 are not easily reconciled with
      conditioned-reinforcement or discriminative-stimulus accounts of the role of
      terminal-link cues. Rather, terminal-link cues appear to decrease sensitivity to
      initial-link contingencies.

PMID- 16812749
TI  - Formation of transitivity in conditional matching to sample by pigeons.
AB  - Four homing pigeons were trained over 5 months in a zero-delay, "arbitrary"
      matching-to-sample procedure with sample and comparison stimuli presented on any
      of three response keys. Birds were also required to complete a fixed-ratio 10
      requirement on both sample and comparison stimuli to terminate their
      presentation. The procedure resulted in the establishment of relations that were
      not specifically trained and that can be characterized by the property of
      transitivity in a stimulus equivalence context. This result was in contrast with
      the findings obtained from most previous research with nonhuman subjects.

PMID- 16812750
TI  - Resistance to reinforcement change in multiple and concurrent schedules assessed
      in transition and at steady state.
AB  - Behavioral momentum theory relates resistance to change of responding in a
      multiple-schedule component to the total reinforcement obtained in that
      component, regardless of how the reinforcers are produced. Four pigeons responded
      in a series of multiple-schedule conditions in which a variable-interval 40-s
      schedule arranged reinforcers for pecking in one component and a variable
      interval 360-s schedule arranged them in the other. In addition, responses on a
      second key were reinforced according to variable-interval schedules that were
      equal in the two components. In different parts of the experiment, responding was
      disrupted by changing the rate of reinforcement on the second key or by
      delivering response-independent food during a blackout separating the two
      components. Consistent with momentum theory, responding on the first key in Part
      1 changed more in the component with the lower reinforcement total when it was
      disrupted by changes in the rate of reinforcement on the second key. However,
      responding on the second key changed more in the component with the higher
      reinforcement total. In Parts 2 and 3, responding was disrupted with free food
      presented during intercomponent blackouts, with extinction (Part 2) or variable
      interval 80-s reinforcement (Part 3) arranged on the second key. Here, resistance
      to change was greater for the component with greater overall reinforcement.
      Failures of momentum theory to predict short-term differences in resistance to
      change occurred with disruptors that caused greater change between steady states
      for the richer component. Consistency of effects across disruptors may yet be
      found if short-term effects of disruptors are assessed relative to the extent of
      change observed after prolonged exposure.

PMID- 16812751
TI  - Delayed matching-to-sample performance: Effects of relative reinforcer frequency
      and of signaled versus unsignaled reinforcer magnitudes.
AB  - Six pigeons were trained on a delayed red-green matching-to-sample task that
      arranged four delays within sessions. Matching responses intermittently produced
      either 1.5-s access to food or 4.5-s access to food, and nonmatching responses
      produced either 1.5-s or 4.5-s blackout. Two phases were conducted: a signaled
      phase in which the reinforcer magnitudes (small and large) were signaled by
      houselights (positioned either on the left or right of the chamber), and an
      unsignaled phase in which there was no correlation between reinforcer magnitude
      and houselight position. In both phases, the relative frequency with which red
      and green matching responses produced food was varied across five values. Both
      matching accuracy and the sensitivity of performance to the distribution of
      reinforcers for matching responses decreased with increasing delays in both
      phases. In addition, accuracy and reinforcer sensitivity were significantly lower
      on signaled small-reinforcer trials compared with accuracy and sensitivity values
      on signaled large-reinforcer trials and on both types of unsignaled trials. These
      results are discussed in the context of research on both nonhuman animal and
      human memory.

PMID- 16812752
TI  - Human symbolic matching-to-sample performance: Effects of reinforcer and sample
      stimulus probabilities.
AB  - Four experiments, each with 6 human subjects, varied the distribution of
      reinforcers for correct responses and the probability of sample-stimulus
      presentation in symbolic matching-to-sample procedures. Experiment 1 held the
      sample-stimulus probability constant and varied the ratio of reinforcers obtained
      for correct responses on the two alternatives across conditions. There was a
      positive relation between measures of response bias and the ratio of reinforcers.
      Experiment 2 held the ratio of reinforcers constant and varied the sample
      stimulus probability across conditions. Unlike previous studies that used pigeons
      as subjects, there was a negative relation between bias and the ratio of sample
      stimulus presentations. In Experiment 3, the sample-stimulus probability and the
      reinforcer ratio covaried across conditions. Response bias did not vary
      systematically across conditions. In Experiments 1 to 3, correct responses were
      reinforced intermittently. Experiment 4 used the same procedure as Experiment 3,
      but all correct responses now produced some scheduled consequence. There was a
      positive relation between response bias and the ratio of reinforcers. The results
      suggest that human performance in these tasks was controlled by both the relative
      frequency of reinforced responses and the relative frequency of nonreinforced
      responses.

PMID- 16812753
TI  - Changeover delay and concurrent-schedule performance in domestic hens.
AB  - Six domestic hens were exposed to a series of five pairs of two-key concurrent
      variable-interval schedules with a range of changeover delays from no delay to 15
      s. Times spent responding on each alternative and total, within_, and post
      changeover-delay response ratios were analyzed in terms of the generalized
      matching law. The sensitivity parameters, a, for response and time data were
      generally low when no changeover delay was programmed but were not 0.0. They were
      higher for all other changeover-delay values, with some tendency to increase as
      the changeover delay lengthened at very short delays. Within-delay responding was
      insensitive to reinforcement-rate differences at all changeover delays (a values
      close to 0.0). As a result of this insensitivity, post-changeover-delay
      responding was more sensitive to reinforcement-rate changes than was total
      responding. Interchangeover intervals increased systematically with changeover
      delay duration. Responding, particularly after the changeover delay, was well
      predicted by an equation based on a reinforcer-loss model.

PMID- 16812754
TI  - Predicting and scaling hens' preferences for topographically different responses.
AB  - Six hens were exposed to several concurrent (second-order) variable-interval
      schedules in which the response requirements on the alternatives were varied. The
      response requirements were one key peck versus five key pecks, one key peck
      versus one door push, and five key pecks versus one door push. Response- and time
      allocation ratios undermatched the obtained reinforcement ratios but were well
      described by the generalized matching law. Time and response bias estimates from
      two pairs of response requirements were used to predict bias in the third
      pairing. The predicted values were close to those obtained; this result supports
      the notion that both numerically and topographically different responses act as
      constant sources of bias within the generalized matching law. The differences
      between the response and time biases could be accounted for by the different
      times needed to complete each response requirement. The results also suggest that
      the door push is a useful operant for research with domestic hens.

PMID- 16812755
TI  - Pigeons' discrimination of paintings by Monet and Picasso.
AB  - Pigeons successfully learned to discriminate color slides of paintings by Monet
      and Picasso. Following this training, they discriminated novel paintings by Monet
      and Picasso that had never been presented during the discrimination training.
      Furthermore, they showed generalization from Monet's to Cezanne's and Renoir's
      paintings or from Picasso's to Braque's and Matisse's paintings. These results
      suggest that pigeons' behavior can be controlled by complex visual stimuli in
      ways that suggest categorization. Upside-down images of Monet's paintings
      disrupted the discrimination, whereas inverted images of Picasso's did not. This
      result may indicate that the pigeons' behavior was controlled by objects depicted
      in impressionists' paintings but was not controlled by objects in cubists'
      paintings.

PMID- 16812756
TI  - Stimulus control in the use of landmarks by pigeons in a touch-screen task.
AB  - Pigeons were tested in a search task on the surface of a monitor on which their
      responses were registered by a touch-sensitive device. A graphic landmark array
      was presented consisting of a square outline (the frame) and a colored
      "landmark." The unmarked goal, pecks at which produced reward, was located near
      the center of one edge of the frame, and the landmark was near it. The entire
      array was displaced without rotation on the monitor from trial to trial. On
      occasional no-reward tests, the following manipulations were made to the landmark
      array: (a) either the frame or the landmark was removed; (2) either one edge of
      the frame or the landmark was shifted; and (3) two landmarks were presented with
      or without the frame present. On these two-landmark tests, the frame, when
      present, defined which was the "correct" landmark. When the frame was absent, the
      "correct" landmark was arbitrarily determined. Results showed that pecks of 2
      pigeons were controlled almost solely by the landmark, pecks of 3 were controlled
      primarily by the landmark but the frame could distinguish the correct landmark,
      and 1 bird's behavior was controlled primarily by the frame. Stimulus control in
      this search task is thus selective and differs across individuals. Comparisons to
      other search tasks and to other stimulus control experiments are made.

PMID- 16812757
TI  - Contrast and reallocation of extraneous reinforcers as a function of component
      duration and baseline rate of reinforcement.
AB  - Four pigeons responded on multiple schedules arranged on a "main" key in a two
      key experimental chamber. A constant schedule component was alternated with
      another component that was varied over conditions. On an extra response key,
      conjoint schedules of reinforcement that operated in both components were
      arranged concurrently with the multiple schedule on the main key. On the main
      key, changes in reinforcement rate in the varied component were inversely related
      to changes in response rates in the constant component (behavioral contrast). On
      the extra key, some reinforcers were reallocated between components, depending on
      the schedules in effect on the main key in the varied component. In the varied
      component, the obtained rates of reinforcement on the extra key were inversely
      related to main-key reinforcement rate. In the constant component, extra-key
      reinforcer rates were positively related to main-key reinforcer rates obtained in
      the varied component, and were not a function of response rates on the extra key.
      In two comparisons, the rate at which components alternated and the value of the
      main-key schedule in the constant component were varied. Consistent with earlier
      work, long components reduced the extent of contrast. Reductions in contrast as a
      function of component duration were accompanied by similar reductions in the
      extent of reinforcer reallocation on the extra key. In the second comparison,
      lowering the rate of reinforcement in the constant component increased the rate
      at which extra-key reinforcers were obtained, reduced the extent of reinforcer
      reallocation, and reduced contrast. Overall, the results are consistent with the
      suggestion that some contrast effects are due to the changes in extraneous
      reinforcement during the constant component, and that manipulations of component
      duration, and manipulations of the rate of reinforcement in the constant
      component, affect contrast because they influence the extent of extraneous
      reinforcer real-location.

PMID- 16812758
TI  - Reversal of baseline relations and stimulus equivalence: I. Adults.
AB  - Following the emergence of two four-member equivalence classes (A1B1C1D1 and
      A2B2C2D2), 5 students were exposed to a series of phases including a baseline
      conditional discrimination reversal (i.e., choosing D2 was reinforced and D1
      punished given Sample A1; choosing D1 was reinforced and D2 punished given Sample
      A2), the delayed introduction of CD/DC transitivity/equivalence probes, DE
      conditional discrimination training, a second baseline conditional discrimination
      reversal (i.e., choosing C2 was reinforced given B1, etc.), and a return to
      original baseline reinforcement contingencies. Results showed that baseline and
      symmetry probe performances were extremely sensitive to baseline modifications.
      In contrast, patterns on transitivity/equivalence probes remained predominantly
      consistent with the originally established equivalence classes, although there
      were exceptions on some E probe relations for 2 subjects. The dissociation
      between baseline and symmetry versus transitivity/equivalence patterns may have
      important implications because it is not easily accounted for by current models
      of equivalence phenomena.

PMID- 16812760
TI  - Prisoner's dilemma and the pigeon: Control by immediate consequences.
AB  - In three experiments pigeons played (i.e., chose between two colored keys)
      iterated prisoner's dilemma and other 2 x 2 games (2 participants and 2 options)
      against response strategies programmed on a computer. Under the prisoner's
      dilemma pay-off matrix, the birds generally defected (i.e., pecked the color
      associated with not cooperating) against both a random response (.5 probability
      of either alternative) and a tit-for-tat strategy (on trial n the computer
      "chooses" the alternative that is the same as the one chosen by the subject on
      trial n - 1) played by the computer. They consistently defected in the tit-for
      tat condition despite the fact that as a consequence they earned about one third
      of the food that they could have if they had cooperated (i.e., pecked the
      "cooperate" color) on all the trials. Manipulation of the values of the food pay
      offs demonstrated that the defection and consequent loss of food under the tit
      for-tat condition were not due to a lack of sensitivity to differences in pay-off
      values, nor to strict avoidance of a null pay-off (no food on a trial), nor to
      insensitivity to the local (current trial) reward contingencies. Rather, the
      birds markedly discounted future outcomes and thus made their response choices
      based on immediate outcomes available on the present trial rather than on long
      term delayed outcomes over many trials. That is, the birds were impulsive,
      choosing smaller but more immediate rewards, and did not demonstrate self
      control. Implications for the study of cooperation and competition in both humans
      and nonhumans are discussed.

PMID- 16812759
TI  - Independence of reinforcement delay and magnitude in concurrent chains.
AB  - A three-component concurrent-chains procedure was used to investigate preference
      between terminal-link schedules that differed in delay and magnitude of
      reinforcement. Response and time allocation data were well described by a
      generalized matching model. Sensitivity to delay appeared to be lower when
      reinforcement magnitudes were unequal than when they were equal, but when
      obtained rather than programmed time spent responding in the initial links was
      used in the model, the difference vanished. The results support independence of
      delay and magnitude as separate dimensions of reinforcement value, as required by
      the matching law, and the assumption of the contextual choice model (Grace, 1994)
      that sensitivities to delay and magnitude are affected similarly by temporal
      context. Although there was statistical evidence for interaction between
      successive components, the effects were small and transient. The multiple
      component concurrent-chains procedure should prove useful in future research on
      multidimensional preference, although it may be necessary to control obtained
      initial-link time more precisely.

PMID- 16812761
TI  - Delayed matching-to-sample performance of hens: Effects of sample duration and
      response requirements during the sample.
AB  - Six domestic hens were trained under a delayed matching-to-sample procedure with
      red and green keylights as sample and comparison stimuli and a 1.5-s delay
      interval. The hens were trained to stop pecking the sample stimuli when a tone
      sounded. Duration of the sample stimuli (2 to 10 s) and the number of pecks
      required on the key on which these stimuli were presented (0 to 10) were altered
      across conditions. Both the response requirement on the sample key and the
      duration of sample presentations affected accuracy. These findings are in
      agreement with those of earlier studies using other species and somewhat
      different procedures.

PMID- 16812762
TI  - Self-control and impulsiveness in children and adults: Effects of food
      preferences.
AB  - Experiment 1 used 6 preschool boys and Experiment 2 used 6 adult women to explore
      the effects of food preference on humans' choice in self-control paradigms. The
      boys showed a higher proportion of responses for more delayed, larger reinforcers
      (a measure of self-control) when those choices resulted in receipt of the most
      preferred food compared to when those choices resulted in the least preferred
      food. Further, the boys chose the less delayed, smaller reinforcers significantly
      more often when only those choices, as opposed to both choices, resulted in the
      most preferred food. Conversely, they chose the more delayed, larger reinforcers
      significantly more often when only those choices, as opposed to both choices,
      resulted in the most preferred food. Finally, the women demonstrated
      significantly less sensitivity to reinforcer amount relative to sensitivity to
      reinforcer delay (another measure of self-control) when they had a higher
      preference for the juice received as the less delayed, smaller reinforcer than
      for the juice received as the more delayed, larger reinforcer. Together, the
      results show that subjects' food preferences can influence self-control for food
      reinforcers.

PMID- 16812763
TI  - Within-session changes in key and lever pressing for water during several
      multiple variable-interval schedules.
AB  - Rats pressed keys or levers for water reinforcers delivered by several multiple
      variable-interval schedules. The programmed rate of reinforcement varied from 15
      to 240 reinforcers per hour in different conditions. Responding usually increased
      and then decreased within experimental sessions. As for food reinforcers, the
      within-session changes in both lever and key pressing were smaller, peaked later,
      and were more symmetrical around the middle of the session for lower than for
      higher rates of reinforcement. When schedules provided high rates of
      reinforcement, some quantitative differences appeared in the within-session
      changes for lever and key pressing and for food and water. These results imply
      that basically similar factors produce within-session changes in responding for
      lever and key pressing and for food and water. The nature of the reinforcer and
      the choice of response can also influence the quantitative properties of within
      session changes at high rates of reinforcement. Finally, the results show that
      the application of Herrnstein's (1970) equation to rates of responding averaged
      over the session requires careful consideration.

PMID- 16812764
TI  - Maintained nodal-distance effects in equivalence classes.
AB  - Twelve subjects were trained to select one of two stimuli from a pair (the B
      pair) when presented with one of two stimuli from another pair (the A pair), thus
      establishing two AB relations, A1-B1 and A2-B2. In a similar fashion, additional
      stimuli were used to establish BC, CD, and DE relations. Trials used to train all
      relations occurred in each session. Once performances were established, probe
      trials were introduced that tested for the emergence of untrained relations
      (e.g., B1-D1 or A1-E1). These emergent relations were categorized according to
      nodal distance (i.e., the number of stimuli across which transitivity would have
      to hold in order for the relation to emerge). For example, a test for A2-C2
      crosses one node (B2), whereas a test for A1-E1 crosses three nodes (B1, C1, and
      D1). Only 2 of the subjects formed equivalence classes. The evocation of class
      appropriate responding by each emergent-relation probe was an inverse function of
      nodal distance for all 12 subjects. In addition, performance on the originally
      trained relations was disrupted by the introduction of probes. The 2 subjects who
      exhibited equivalence classes were then trained to make different numbers of key
      presses in the presence of each of the four A and E stimuli. In a response
      transfer test, the B, C, and D stimuli evoked the responses trained to the A and
      E stimuli in the same equivalence class. Likelihood of class-appropriate
      responses was an inverse function of nodal distance, and this pattern persisted
      across testing. Reaction times in the transfer test were an inverted U-shaped
      function of nodal distance. Because training of the baseline relations occurred
      concurrently and the B, C, and D stimuli were presented an equal number of times
      before the transfer test, the test performances illustrate effects of nodal
      distance that were not confounded by order or amount of experience with the
      stimuli. The results imply that ordered, sequential exposure to individual
      stimulus relations may facilitate the development of equivalence classes and that
      the relatedness of stimuli within an equivalence class is a relatively permanent
      inverse function of nodal distance.

PMID- 16812765
TI  - A quantitative analysis of extreme choice.
AB  - Six homing pigeons were trained on a variety of concurrent variable-interval
      schedules in a switching-key procedure. Unlike previous work, reinforcer ratios
      of up to 160 to 1 and concurrent extinction variable-interval schedules were
      arranged in order to investigate choice when reinforcer-frequency outcomes were
      extremely different. The data obtained over 11 conditions were initially analyzed
      according to the generalized matching law, which fitted the data well. The
      generalized matching law was then fitted only to conditions in which the
      reinforcer ratios were between 1 to 10 and 10 to 1. The deviations of choice
      measures from the other four more extreme reinforcer-ratio conditions were
      significantly more towards equal choice than predicted by this second generalized
      matching fit. A contingency-discriminability model, which predicts such
      deviations, described the data more effectively than did the generalized matching
      law, and also correctly predicted the maintenance of responding on both
      alternatives when one was associated with extinction.

PMID- 16812766
TI  - A transformation of self-discrimination response functions in accordance with the
      arbitrarily applicable relations of sameness, more than, and less than.
AB  - In Experiment 1, 2 experimental subjects were given pretraining of nonarbitrary
      relations that brought their responses under the control of four contextual
      stimuli; same, opposite, more than, and less than. One control subject was not
      exposed to this pretraining. The 2 pretrained subjects and the 3rd nonpretrained
      subject then received training in six arbitrary relations, the following four
      relations being the most critical: same/A1-B1, same/A1-C1, less than/A1-B2, more
      than/A1-C2. All 3 subjects were then tested for seven derived relations, the
      following three relations being the most important: same/B1-C1, more than/B1-C2,
      less than/B1-B2. The 2 pretrained subjects, but not the nonpretrained subject,
      showed the derived relations. One of the stimuli (B1) from the relational network
      and two novel stimuli (X1 and X2) were then used to train three different self
      discrimination responses on three complex schedules of reinforcement. That is,
      all 3 subjects were trained to pick X1 if they had not emitted a response, to
      pick B1 if they had emitted one response only, and to pick X2 if they had emitted
      two responses only. The 2 pretrained subjects, but not the nonpretrained subject,
      showed the predicted transformation of self-discrimination response functions in
      accordance with the relations of sameness, more than, and less than (i.e., no
      response, pick B2; one response only, pick C1; and two responses only, pick C2).
      In Experiment 2, 2 new subjects were employed, and the arbitrary relational
      training and testing phases were modified to control for a procedural artifact
      that may have contributed to the results of the first experiment. Experiment 2
      replicated the findings of Experiment 1. The pattern of results support the
      utility of a relational frames approach to understanding derived stimulus
      relations.

PMID- 16812767
TI  - Action at a temporal distance: Component transition as the relational basis for
      successive discrimination.
AB  - In a successive discrimination, red and green hues signaled component variable
      interval schedules. The exponent of the power function relating ratios of
      responses in the red and green components to ratios of reinforcers provided a
      reinforcement-free measure of discrimination or stimulus control. Responses were
      recorded in successive 10-s subintervals of the 50-s components. The power
      function exponent decreased systematically with increasing time since component
      transition in most conditions of five experiments. This reduction was not
      influenced by the absolute rate of reinforcement, consistent with the
      interpretation of the exponent as a measure of stimulus control. A reduction in
      the overall level of stimulus control by increasing the duration of response
      produced keylight offset did not influence the decrease in discrimination with
      increasing time since component transition. The results support the conclusion
      that discriminative responding in successive discriminations is governed by
      several sources of stimulus control including delayed control by component
      transition.

PMID- 16812768
TI  - Discrimination training, partial reinforcement, and increases in intertrial
      interval all reduce response speed in a continuously reinforced key-pecking task.
AB  - Pigeons were trained in a discrete-trial task in which a response to the center
      key obtained illumination of a side key and a single response to the side key
      terminated a trial with either reinforcement or nonreinforcement. Center-key
      speeds (i.e., reciprocals of latencies) declined with increases in intertrial
      interval, and it is argued that this effect is related to a decreased likelihood
      as intertrial interval increases that birds will be near the key at trial onset.
      Side-key speeds on trials with reinforcement decreased both with increases in
      intertrial interval and with shifts from continuous reinforcement to either a
      discrimination or a partial-reinforcement condition. The effects on side-key
      speeds are compared with effects observed in alley-running tasks using rats, and
      an interpretation in terms of frustration theory is offered for the results
      obtained in both types of task.

PMID- 16812769
TI  - Biasing the pacemaker in the behavioral theory of timing.
AB  - In the behavioral theory of timing, pacemaker rate is determined by overall rate
      of reinforcement. A two-alternative free-operant psychophysical procedure was
      employed to investigate whether pacemaker period was also sensitive to the
      differential rate of reinforcement. Responding on a left key during the first 25
      s and on a right key during the second 25 s of a 50-s trial was reinforced at
      variable intervals, and variable-interval schedule values during the two halves
      of the trials were varied systematically. Responding on the right key during the
      first 25 s and on the left key during the second 25 s was not reinforced.
      Estimates of pacemaker period were derived from fits of a function predicted by
      the behavioral theory of timing to right-key response proportions in consecutive
      5-s bins of the 50-s trial. Estimates of pacemaker period were shortest when the
      differential reinforcer rate most strongly favored right-key responses, and were
      longest when the differential reinforcer rate most strongly favored left-key
      responses. The results were consistent with the conclusion that pacemaker rate is
      influenced by relative reinforcer rate.

PMID- 16812770
TI  - Within-session response rates when reinforcement rate is changed within each
      session.
AB  - Three pigeons pecked keys and 5 rats pressed levers for food delivered on
      variable-interval schedules. During baseline conditions, subjects responded on a
      variable-interval 40-s schedule throughout the session. During experimental
      conditions, the programmed rate of reinforcement changed every 10 min in the 50
      min sessions. When rats served as subjects, Herrnstein's (1970) hyperbolic
      equation provided a good description of the relation between rate of responding
      during a 10-min interval and the rate of reinforcement obtained during that
      interval. Responding, measured over 10-min blocks, was also approximately equally
      sensitive to changes in the programmed rate of reinforcement at all times in the
      session. Herrnstein's equation provided a poorer description of the changes in
      responding when pigeons served as subjects. Differences in experimental
      experience or differences in the absolute rates at which subjects responded may
      have contributed to the differences in results for these different species.

PMID- 16812771
TI  - Behavioral economics (Editorial).

PMID- 16812772
TI  - Discounting of delayed rewards: Models of individual choice.
AB  - The present paper addresses the question of the form of the mathematical relation
      between the time until a delayed reward and its present value. Data are presented
      from an experiment in which subjects chose between hypothetical amounts of money
      available either immediately or after a delay (Green, Fry, & Myerson, 1994).
      Analyses of the behavior of individual young adults demonstrated that temporal
      discounting is better described by hyperbola-like functions than by exponential
      decay functions. For most individuals, the parameter that determines the rate of
      discounting varied inversely with amount. Raising the denominator of the
      discounting function to a power resulted in better descriptions of the data from
      most subjects. Two possible derivations of the temporal discounting function are
      proposed, a repeated choice model and an expected value model. These provide
      theoretical interpretations for amount-dependent discounting but amount
      independent exponent parameters.

PMID- 16812773
TI  - How to teach a pigeon to maximize overall reinforcement rate.
AB  - In two experiments deviations from matching earned higher overall reinforcement
      rates than did matching. In Experiment 1 response proportions were calculated
      over a 360-response moving average, updated with each response. Response
      proportions that differed from the nominal reinforcement proportions, by a
      criterion that was gradually increased, were eligible for reinforcement. Response
      proportions that did not differ from matching were not eligible for
      reinforcement. When the deviation requirement was relatively small, the
      contingency proved to be effective. However, there was a limit as to how far
      response proportions could be pushed from matching. Consequently, when the
      deviation requirement was large, overall reinforcement rate decreased and pecking
      was eventually extinguished. In Experiment 2 a discriminative stimulus was added
      to the procedure. The houselight was correlated with the relationship between
      response proportions and the nominal (programmed) reinforcement proportions. When
      the difference between response and reinforcement proportions met the deviation
      requirement, the light was white and responses were eligible for reinforcement.
      When the difference between response and reinforcement proportions failed to
      exceed the deviation requirement, the light was blue and responses were not
      eligible for reinforcement. With the addition of the light, it proved to be
      possible to shape deviations from matching without any apparent limit. Thus, in
      Experiment 2 overall reinforcement rate predicted choice proportions and relative
      reinforcement rate did not. In contrast, in previous experiments on the
      relationship between matching and overall reinforcement maximization, relative
      reinforcement rate was usually the better predictor of responding. The results
      show that whether overall or relative reinforcement rate better predicts choice
      proportions may in part be determined by stimulus conditions.

PMID- 16812774
TI  - Assessing preference for reinforcers using demand curves, work-rate functions,
      and expansion paths.
AB  - A BEHAVIORAL ECONOMIC MODEL THAT EXPLAINS THE CHOICE AND ALLOCATION OF WORK RATE
      IS USED TO PREDICT PERFORMANCE PATTERNS IN THREE CONTEXTS: with single schedules,
      with concurrent schedules when total reinforcement is low, and with concurrent
      schedules when reinforcement increases. Performance in the three contexts is
      predicted to change in orderly ways depending on how the subject evaluates the
      reinforcers earned. Quadrant diagrams are used to generate reinforcer demand
      functions, work-rate supply functions, and reinforcement-rate expansion paths.
      Preference between reinforcers is viewed as being a variable, with preference
      reversing in some situations.

PMID- 16812775
TI  - Behavioral economics and behavioral momentum.
AB  - Some relations between elasticity of demand and the conditions of reinforcement
      are reanalyzed in terms of resistance to change, in ways suggested by the
      metaphor of behavioral momentum; some relations between resistance to change and
      the conditions of reinforcement are reanalyzed in terms of elasticity of demand,
      in ways suggested by behavioral economics. In addition, some data on labor supply
      in relation to variable-ratio schedules and alternative reinforcement are
      reanalyzed in terms of resistance to change and compared with steady-state
      resistance data for performance on multiple and concurrent interval schedules.
      The results of these studies can be summarized by two functions based on the
      behavioral momentum approach, relating relative behavioral mass to relative
      reinforcement per response or per unit time. The former is a relation between
      relative unit price and relative behavioral mass, suggesting the possibility of
      convergent measurement of a theoretical construct common to both approaches.
      However, the momentum and economic approaches differ fundamentally on whether it
      is preferable to construe discriminated operant behavior as selected and
      strengthened by its consequences or as part of a behavior-consequence bundle that
      maximizes utility.

PMID- 16812776
TI  - Economics, ecologics, and mechanics: The dynamics of responding under conditions
      of varying motivation.
AB  - The mechanics of behavior developed by Killeen (1994) is extended to deal with
      deprivation and satiation and with recovery of arousal at the beginning of
      sessions. The extended theory is validated against satiation curves and within
      session changes in response rates. Anomalies, such as (a) the positive
      correlation between magnitude of an incentive and response rates in some contexts
      and a negative correlation in other contexts and (b) the greater prominence of
      incentive effects when magnitude is varied within the session rather than between
      sessions, are explained in terms of the basic interplay of drive and incentive
      motivation. The models are applied to data from closed economies in which changes
      of satiation levels play a key role in determining the changes in behavior.
      Relaxation of various assumptions leads to closed-form models for response rates
      and demand functions in these contexts, ones that show reasonable accord with the
      data and reinforce arguments for unit price as a controlling variable. The
      central role of deprivation level in this treatment distinguishes it from
      economic models. It is argued that traditional experiments should be redesigned
      to reveal basic principles, that ecologic experiments should be redesigned to
      test the applicability of those principles in more natural contexts, and that
      behavioral economics should consist of the applications of these principles to
      economic contexts, not the adoption of economic models as alternatives to
      behavioral analysis.

PMID- 16812777
TI  - Editorial.

PMID- 16812778
TI  - Closed-economy multiple-schedule performance: Effects of deprivation and session
      duration.
AB  - Three pigeons responded for food reinforcement on multiple variable-interval
      schedules in which the total consumption of food was entirely determined by the
      subjects' interaction with the schedules (a closed economy). The finding of
      overmatching, where response allocation between components is more extreme than
      the distribution of reinforcers, was reconfirmed. Generalized-matching
      sensitivity decreased from overmatching to undermatching values typical of
      conventional multiple schedules when food deprivation was increased by decreasing
      session duration, but not when deprivation was increased by decreasing overall
      reinforcer rate. Sensitivity also increased from undermatching to overmatching as
      session duration increased from 100 min to 24 hr, while deprivation was held
      constant by decreasing overall reinforcer rate. These results can be understood
      in terms of increases in the value of extraneous reinforcers relative to food
      reinforcers as deprivation decreases or as the economy for extraneous reinforcers
      becomes more closed. However, no published quantitative expression of the effects
      of extraneous reinforcers is entirely consistent with the results.

PMID- 16812779
TI  - Introduction.

PMID- 16812780
TI  - On the origins of naming and other symbolic behavior.
AB  - We identify naming as the basic unit of verbal behavior, describe the conditions
      under which it is learned, and outline its crucial role in the development of
      stimulus classes and, hence, of symbolic behavior. Drawing upon B. F. Skinner's
      functional analysis and the theoretical work of G. H. Mead and L. S. Vygotsky, we
      chart how a child, through learning listener behavior and then echoic responding,
      learns bidirectional relations between classes of objects or events and his or
      her own speaker-listener behavior, thus acquiring naming-a higher order
      behavioral relation. Once established, the bidirectionality incorporated in
      naming extends across behavior classes such as those identified by Skinner as the
      mand, tact, and intraverbal so that each becomes a variant of the name relation.
      We indicate how our account informs the specification of rule-governed behavior
      and provides the basis for an experimental analysis of symbolic behavior.
      Furthermore, because naming is both evoked by, and itself evokes, classes of
      events it brings about new or emergent behavior such as that reported in studies
      of stimulus equivalence. This account is supported by data from a wide range of
      match-to-sample studies that also provide evidence that stimulus equivalence in
      humans is not a unitary phenomenon but the outcome of a number of different types
      of naming behavior.

PMID- 16812782
TI  - Equivalence relations, naming, and generalized symmetry.

PMID- 16812781
TI  - The evolution of naming-just so!

PMID- 16812783
TI  - Listener behavior and ostensive learning.

PMID- 16812784
TI  - Joint control and word-object bidirectionality.

PMID- 16812785
TI  - On the origins of misguided theories of naming and other symbolic behavior.

PMID- 16812787
TI  - Experimental analysis of naming behavior cannot explain naming capacity.

PMID- 16812786
TI  - Learning names may help to make the right connections.

PMID- 16812788
TI  - Naming as a technical term: Sacrificing behavior analysis at the altar of
      popularity?

PMID- 16812790
TI  - Natural contingencies in the creation of naming as a higher order behavior class.

PMID- 16812789
TI  - Naming, meaning, and verbal operants.

PMID- 16812791
TI  - The evidence for naming as a cause or facilitator of equivalence class formation.

PMID- 16812793
TI  - Can the naming hypothesis be falsified?

PMID- 16812792
TI  - Listening with understanding and speaking with meaning.

PMID- 16812794
TI  - Methodological issues in the study of naming.

PMID- 16812795
TI  - Achieving parity: The role of automatic reinforcement.

PMID- 16812796
TI  - On naming and symbolic behavior: In the beginning was the Name?

PMID- 16812797
TI  - The origins of naming: A critique of self-listening.

PMID- 16812798
TI  - Separate repertoires or naming?

PMID- 16812799
TI  - Thought without naming.

PMID- 16812800
TI  - Names as constituents of sentences: An omission.

PMID- 16812802
TI  - Concurrent schedules: Quantifying the aversiveness of noise.
AB  - Four hens worked under independent multiple concurrent variable-interval
      schedules with an overlaid aversive stimulus (sound of hens in a poultry shed at
      100dBA) activated by the first peck on a key. The sound remained on until a
      response was made on the other key. The key that activated the sound in each
      component was varied over a series of conditions. When the sound was activated by
      the left (or right) key in one component, it was activated by the right (or left)
      key in the other component. Bias was examined under a range of different variable
      interval schedules, and the applicability of the generalized matching law was
      examined. It was found that the hens' behavior was biased away from the sound
      independently of the schedule in effect and that this bias could be quantified
      using a modified version of the generalized matching law. Behavior during the
      changeover delays was not affected by the presence of the noise or by changes in
      reinforcement rate, even though the total response measures were. Insensitivity
      shown during the delay suggests that behavior after the changeover delay may be
      more appropriate as a measure of preference (or aversiveness) of stimuli than are
      overall behavior measures.

PMID- 16812803
TI  - Detecting a nonevent: Delayed presence-versus-absence discrimination in pigeons.
AB  - Eight pigeons were trained on a delayed presence-versus-absence discrimination
      paradigm in which a sample stimulus was presented on some trials but not on
      others. If a sample was presented, then a response to one choice key produced
      food. If no sample was presented, a response to the other choice key produced
      food. The basic finding was that performance remained constant and well above 50%
      correct on no-sample trials as the retention interval increased, whereas
      performance dropped precipitously (to below 50% correct) on sample trials. In the
      second phase of the experiment, all of the trials were no-sample trials, and
      reinforcers were delivered probabilistically for one group of pigeons and
      according to time-based schedules for the other group. The exact reinforcement
      probabilities used in Phase 2 were those calculated to be in effect on no-sample
      trials in Phase 1 (according to a discrete-state model of performance). Subjects
      did not show exclusive preference for the richer alternative on no-sample trials
      in the first phase, but those in the probabilistic group developed near-exclusive
      preference for the richer alternative during the second phase. These data are
      inconsistent with the predictions of the discrete-state model, but are easily
      accommodated by an account based on signal detection theory, which also can be
      applied effectively to discrimination of event duration and the "subjective
      shortening" effect.

PMID- 16812801
TI  - Reflections on naming and other symbolic behavior.

PMID- 16812804
TI  - Effects of reinforcement amount on attack induced under a fixed-interval schedule
      in pigeons.
AB  - Key pecking by pigeons was maintained on a chained fixed-interval 4-min (12-min
      for 1 subject) fixed-ratio 1 schedule of food presentation. Attacks toward a
      restrained and protected conspecific were recorded. In the first experiment, the
      amount of food presented per interval was manipulated across phases by varying
      the number of fixed ratios required in the terminal link of the chain. Measures
      of attack for all pigeons during the fixed-interval component increased
      monotonically as a function of food amount. In the second experiment, two
      different food amounts alternated within each experimental session under a
      multiple schedule. For both pigeons in this experiment, measures of attack were
      higher during the component that delivered the larger food amount per interval.
      The differences in levels of attack induced by the two food amounts in Experiment
      2, however, were not as great as in Experiment 1; apparently this was because
      attack during the first interval of each component was controlled in part (P
      5626) or entirely (P-7848) by the reinforcement amount delivered at the end of
      the previous component. Attack was also a function of the location of the
      interfood interval within the session. For both pigeons, attack tended to
      decrease throughout the session. The results of both experiments suggest that
      attack is an increasing function of reinforcement amount under fixed-interval
      schedules, but that this function may be influenced by the manner in which
      reinforcement amount is manipulated, by the duration of the interfood interval,
      and by the location of the interfood interval within the experimental session. In
      general, these results are compatible with theories of induced attack and other
      schedule-induced behavior that emphasize aversive after-effects of reinforcement
      presentation.

PMID- 16812805
TI  - Residence time and choice in concurrent foraging schedules.
AB  - Five pigeons were trained on a concurrent-schedule analogue of the "some patches
      are empty" procedure. Two concurrently available alternatives were arranged on a
      single response key and were signaled by red and green keylights. A subject could
      travel between these alternatives by responding on a second yellow "switching"
      key. Following a changeover to a patch, there was a probability (p) that a single
      reinforcer would be available on that alternative for a response after a time
      determined by the value of lambda, a probability of reinforcement per second. The
      overall scheduling of reinforcers on the two alternatives was arranged
      nonindependently, and the available alternative was switched after each
      reinforcer. In Part 1 of the experiment, the probabilities of reinforcement,
      rho(red) and rho(green), were equal on the two alternatives, and the arranged
      arrival rates of reinforcers, lambda(red) and lambda(green), were varied across
      conditions. In Part 2, the reinforcer arrival times were arranged to be equal,
      and the reinforcer probabilities were varied across conditions. In Part 3, both
      parameters were varied. The results replicated those seen in studies that have
      investigated time allocation in a single patch: Both response and time allocation
      to an alternative increased with decreasing values of lambda and with increasing
      values of rho, and residence times were consistently greater than those that
      would maximize obtained reinforcer rates. Furthermore, both response- and time
      allocation ratios undermatched mean reinforcer-arrival time and reinforcer
      frequency ratios.

PMID- 16812806
TI  - Concurrent choice: Effects of overall reinforcer rate and the temporal
      distribution of reinforcers.
AB  - Six pigeons responded on a series of concurrent exponential variable-interval
      schedules, offering a within-subject comparison with previously published data
      from concurrent arithmetic variable-interval schedules. Both relative and overall
      reinforcer rates were varied between conditions. The generalized matching law
      described the data well, with undermatching much more frequent than strict
      matching. Time-allocation sensitivity consistently exceeded response-allocation
      sensitivity for both schedule types, and exponential-schedule sensitivity
      exceeded arithmetic-schedule sensitivity for both measures of choice. A further
      set of conditions using variable-interval schedules whose shortest interval was
      correlated with the mean interval, like arithmetic schedules, but that provided a
      constant conditional probability of reinforcement, like exponential schedules,
      produced sensitivities between those produced by conventional arithmetic and
      exponential schedules. Unlike previous arithmetic-schedule results, exponential
      sensitivity changed nonmonotonically with changes in overall reinforcer rate. The
      results clarify our knowledge of the effects of arithmetic and exponential
      schedules but confuse our understanding of the effects of overall reinforcer rate
      on concurrent choice.

PMID- 16812807
TI  - Changeover behavior and preference in concurrent schedules.
AB  - Pigeons were trained on a multiple schedule of reinforcement in which separate
      concurrent schedules occurred in each of two components. Key pecking was
      reinforced with milo. During one component, a variable-interval 40-s schedule was
      concurrent with a variable-interval 20-s schedule; during the other component, a
      variable-interval 40-s schedule was concurrent with a variable-interval 80-s
      schedule. During probe tests, the stimuli correlated with the two variable
      interval 40-s schedules were presented simultaneously to assess preference,
      measured by the relative response rates to the two stimuli. In Experiment 1, the
      concurrently available variable-interval 20-s schedule operated normally; that
      is, reinforcer availability was not signaled. Following this baseline training,
      relative response rate during the probes favored the variable-interval 40-s
      alternative that had been paired with the lower valued schedule (i.e., with the
      variable-interval 80-s schedule). In Experiment 2, a signal for reinforcer
      availability was added to the high-value alternative (i.e., to the variable
      interval 20-s schedule), thus reducing the rate of key pecking maintained by that
      schedule but leaving the reinforcement rate unchanged. Following that baseline
      training, relative response rates during probes favored the variable-interval 40
      s alternative that had been paired with the higher valued schedule. The reversal
      in the pattern of preference implies that the pattern of changeover behavior
      established during training, and not reinforcement rate, determined the
      preference patterns obtained on the probe tests.

PMID- 16812808
TI  - Response-independent food delivery and behavioral resistance to change.
AB  - Response-independent food was delivered during a dark-key phase between two
      multiple-schedule components to explore its disruptive effects on responding.
      Responding in components was maintained by separate variable-interval 120-s
      schedules, with a 2-s reinforcer in Component 1 and a 6-s reinforcer in Component
      2. Across conditions the rate and duration of response-independent food
      presentations were manipulated. The results showed that response rates in both
      components decreased as a function of the duration and the rate of response
      independent food presentations; moreover, the decrease in response rate relative
      to the baseline level was larger in Component 1 than in Component 2. These
      findings were consistent with expectations from behavioral momentum theory, which
      predicts that if equal disruption (response-independent food in this case) is
      applied to responding in two components, then the ratio of response-rate change
      in Component 1 versus Component 2 should remain constant, irrespective of the
      magnitude of that disruption.

PMID- 16812809
TI  - Types of responding in a signal-detection task.
AB  - Four pigeons were trained to discriminate between two line orientations in a two
      alternative forced-choice procedure. The distribution of reinforcers for the two
      types of correct response was varied across conditions. Performance on each trial
      was recorded separately, including the time taken to make a choice response.
      Discriminability and response-bias measures were calculated for overall
      performance, and, following a median split of the data from each condition, for
      faster and slower choice responses in each condition. Discriminability between
      the stimuli did not vary systematically as a function of choice latency.
      Variations of the reinforcer distributions produced larger response biases for
      the faster responses than for the slower responses. Responses on trials following
      reinforcers were faster and showed a greater effect of the reinforcer
      distribution than did other responses. Behavioral models of signal detection
      should consider the speed of the choice response as a factor modulating the
      effects of reinforcer distributions.

PMID- 16812810
TI  - Blocking, unblocking, and overexpectation in autoshaping with pigeons.
AB  - Three experiments used pigeons in an autoshaping procedure and a single-subject
      design to examine compound stimulus control in classical conditioning. Experiment
      1 examined the blocking effect, and Experiment 2 examined the unblocking effect.
      In both experiments, response-independent food was first delivered intermittently
      in the presence of one distinctively colored houselight but not another. Then,
      conventional autoshaping trials were carried out in the presence of each
      houselight. In Experiment 1, the keylight readily elicited responding in the
      presence of the houselight that had been negatively correlated with food, but not
      in the presence of the houselight that had been positively correlated with food.
      In Experiment 2, the keylight readily elicited responding in the presence of the
      houselight positively correlated with food, but only when the amount of food used
      on the autoshaping trials was either greater or less than that previously
      delivered in the presence of the houselight. Experiment 3 examined the
      overexpectation effect. Conventional autoshaping trials were first carried out by
      presenting each of two keylights individually. Then, additional autoshaping
      trials were carried out by presenting the two keylights as a compound, with
      either the same amount of food or a greater amount of food per trial. Finally,
      the keylights were retested by again presenting them individually. The number of
      responses per trial elicited by the keylights decreased when the amount of food
      used in compound trials was the same as that used in individual trials. However,
      the number of responses per trial remained approximately the same when the amount
      of food used in compound trials was greater than that used in individual trials.
      Taken together, the results of the three experiments demonstrate (a) the
      generality of the blocking, unblocking, and overexpectation effects by virtue of
      their extension to appetitive unconditioned stimuli; (b) the suitability of
      pigeons as subjects and autoshaping as a procedure for studying classical
      conditioning; and (c) the appropriateness of single-subject designs.

PMID- 16812811
TI  - Dynamics of waiting in pigeons.
AB  - Two experiments used response-initiated delay schedules to test the idea that
      when food reinforcement is available at regular intervals, the time an animal
      waits before its first operant response (waiting time) is proportional to the
      immediately preceding interfood interval (linear waiting; Wynne & Staddon, 1988).
      In Experiment 1 the interfood intervals varied from cycle to cycle according to
      one of four sinusoidal sequences with different amounts of added noise. Waiting
      times tracked the input cycle in a way which showed that they were affected by
      interfood intervals earlier than the immediately preceding one. In Experiment 2
      different patterns of long and short interfood intervals were presented, and the
      results implied that waiting times are disproportionately influenced by the
      shortest of recent interfood intervals. A model based on this idea is shown to
      account for a wide range of results on the dynamics of timing behavior.

PMID- 16812812
TI  - Response-dependent prechoice effects on foraging-related choice.
AB  - Three experiments explored the influence of prechoice events on pigeons'
      preference. In two of three studies, a fixed-interval 200-second prechoice period
      preceded the initial links of a concurrent chain in which outcomes differed
      either (a) in terms of the delay to food or (b) in terms of amount of food and
      delay to food. In Experiment 3, the prechoice period preceded the initial links
      that provided a choice between a small single food presentation and two
      identical, more delayed food presentations. In all three cases, obtained choice
      proportions did not vary as a function of prechoice duration. These results
      suggest that a local-contextual view adequately describes the foraging context;
      they also have implications for the appropriate formulation of the delay
      reduction theory of conditioned reinforcement and rate-maximizing views of
      optimal foraging theory.

PMID- 16812813
TI  - Fred s. Keller: rememberings.

PMID- 16812814
TI  - Editor for behavioral pharmacology.

PMID- 16812815
TI  - Choice As A Function Of Reinforcement Ratios In Delayed Matching-to-sample.

PMID- 16812817
TI  - Within-session Changes In Responding During Autoshaping And Automaintenance
      Procedures.

PMID- 16812816
TI  - Pointing At Smaller Food Amounts In An Analogue Of Boysen And Berntson's (1995)
      Procedure.

PMID- 16812818
TI  - Goodbye teacher, good old friend.

PMID- 16812819
TI  - Within-session Changes In Responding During Concurrent Variable-interval
      Schedules.

PMID- 16812820
TI  - Differences in delay, not ratios, control choice in concurrent chains.

PMID- 16812821
TI  - Stimulus Effects On Behavior Allocation In Three-alternative Choice.

PMID- 16812823
TI  - Within-session Response Patterns On Conjoint Variable-interval Variable-time
      Schedules.

PMID- 16812822
TI  - Resistance To Change As A Function Of Stimulus-reinforcer And Location-reinforcer
      Contingencies.

PMID- 16812824
TI  - Separating The Effects Of Trial-specific And Average Sample-stimulus Duration In
      Delayed Matching To Sample In Pigeons.

PMID- 16812825
TI  - Human Signal-detection Performance: Effects Of Signal Presentation Probabilities
      And Reinforcer Distributions.

PMID- 16812827
TI  - Effects of response type on pigeons' sensitivity to variation in reinforcer
      amount and reinforcer delay.

PMID- 16812826
TI  - JEAB And JABA On The World Wide Web: A Report To Readers (Editorial).

PMID- 16812828
TI  - Assessment and choice: an operant simulation of foraging in patches.

PMID- 16812829
TI  - Investigating Behavioral Dynamics With A Fixed-time Extinction Schedule And
      Linear Analysis.

PMID- 16812831
TI  - Open versus closed economies: performance of domestic hens under fixed ratio
      schedules.

PMID- 16812830
TI  - On the relation between preference and resistance to change.

PMID- 16812832
TI  - Residence time in concurrent foraging with fixed times to prey arrival.

PMID- 16812834
TI  - I agree.

PMID- 16812833
TI  - Learning about food: starlings, skinner boxes, and earthworms.

PMID- 16812835
TI  - Beyond the moment: complex behavior in temporally extended environments.

PMID- 16812836
TI  - In Today's Climate, A Forecast For Change: A commentary On Donahoe, Palmer, And
      Burgos.

PMID- 16812837
TI  - We also need complete behavioral models.

PMID- 16812838
TI  - The eternal antithesis: a commentary on donahoe, palmer, and burgos.

PMID- 16812840
TI  - The role of motivation in the s-R issue.

PMID- 16812839
TI  - Units of analysis and the environmental control of behavior.

PMID- 16812841
TI  - Some thoughts on the s-R issue and the relation between behavior analysis and
      behavioral neuroscience.

PMID- 16812843
TI  - Melioration and contiguity.

PMID- 16812842
TI  - Theory and behavior analysis: commentary on donahoe, palmer, and burgos.

PMID- 16812845
TI  - The unit of selection: what do reinforcers reinforce?

PMID- 16812844
TI  - What is learned? Revisiting an old issue.

PMID- 16812846
TI  - Effects Of Histories Of Differential Reinforcement Of Response Rate On Variable
      interval Responding.

PMID- 16812847
TI  - Using the simultaneous protocol to study equivalence class formation: the
      facilitating effects of nodal number and size of previously established
      equivalence classes.

PMID- 16812848
TI  - Varieties of contrast: a review of incentive relativity by charles f. Flaherty.

PMID- 16812849
TI  - Matching-to-sample Performance In Rats: A Case Of Mistaken Identity?

PMID- 16812850
TI  - Erratum.

PMID- 16812851
TI  - Transfer tests of stimulus value in concurrent chains.

PMID- 16812852
TI  - Incongruous stimulus pairing and conditional discrimination training: effects on
      relational responding.

PMID- 16812853
TI  - Schedule interactions involving punishment with pigeons and humans.

PMID- 16812855
TI  - Nonstable concurrent choice in pigeons.

PMID- 16812854
TI  - Comparing Locomotion With Lever-press Travel In An Operant Simulation Of
      Foraging.

PMID- 16812856
TI  - Editor's Introduction.

PMID- 16812857
TI  - Analyzing derived stimulus relations requires more than the concept of stimulus
      class.

PMID- 16812858
TI  - The role of joint control in the development of naming.

PMID- 16812859
TI  - An archeology of meaning.

PMID- 16812860
TI  - What's In A Name? Equivalence By Any Other Name Would Smell As Sweet.

PMID- 16812861
TI  - Equivalence relations.

PMID- 16812862
TI  - Standard principles, nonstandard data, and unsolved issues.

PMID- 16812864
TI  - How, then, shall we characterize this elephant?

PMID- 16812863
TI  - Toward a theory of verbal behavior.

PMID- 16812865
TI  - Contiguity and conditioned reinforcement in probabilistic choice.

PMID- 16812867
TI  - Response-independent Events In The Behavior Stream.

PMID- 16812866
TI  - The control of choice by its consequences.

PMID- 16812868
TI  - Ellen p. Reese (1926-1997): teacher, mentor, and respectful student of human and
      nonhuman behavior.

PMID- 16812869
TI  - Performance On Concurrent Variable-interval Extinction Schedules.

PMID- 16812870
TI  - Tradeoffs in choice between risk and delay depend on monetary amounts.

PMID- 16812871
TI  - On the functions of the changeover delay.

PMID- 16812873
TI  - Habituation To The Reinforcer May Contribute To Multiple-schedule Behavioral
      Contrast.

PMID- 16812872
TI  - Reporting contingencies of reinforcement in concurrent schedules.

PMID- 16812874
TI  - What does a pigeon see in a picasso?

PMID- 16812875
TI  - Group choice: competition, travel, and the ideal free distribution.

PMID- 16812876
TI  - Effects of unsignaled delay of reinforcement on preference and resistance to
      change.

PMID- 16812877
TI  - Effects of reward distribution and performance feedback on competitive
      responding.

PMID- 16812878
TI  - Run length, visit duration, and reinforcers per visit in concurrent performance.

PMID- 16812879
TI  - Effects Of Varying Sample- And Choice-stimulus Disparity On Symbolic Matching-to
      sample Performance.

PMID- 16812880
TI  - Behavior analysis and decision making.

PMID- 16812881
TI  - Effects of consequences of advice on patterns of rule control and rule choice.

PMID- 16812882
TI  - Response Form, Force, And Number: Effects On Concurrent-schedule Performance.

PMID- 16812883
TI  - Effects Of Fixed-interval Schedule And Reinforcer Duration On Responding
      Reinforced By The Opportunity To Run.

PMID- 16812884
TI  - Stimulus Equivalence: Effects Of A Default-response Option On Emergence Of
      Untrained Stimulus Relations.

PMID- 16812885
TI  - Response persistence under ratio and interval reinforcement schedules.

PMID- 16812886
TI  - Greatness and misery in the teaching of the psychology of learning.

PMID- 16812887
TI  - Categorization of natural movements by pigeons: visual concept discrimination and
      biological motion.

PMID- 16812888
TI  - A Century Of Effect: Legacies Of E. L. Thorndike's Animal Intelligence Monograph.

PMID- 16812889
TI  - Operants Were Never "Emitted," Feeling Is Doing, And Learning Takes Only One
      Trial: A Review Of B. F. Skinner's Recent Issues In The Analysis Of Behavior.

PMID- 16812890
TI  - The Matching Law And Amount-dependent Exponential Discounting As Accounts Of Self
      control Choice.

PMID- 16812891
TI  - Preference after training with differential changeover delays.

PMID- 16812892
TI  - A local model of concurrent performance.

PMID- 16812893
TI  - Optimality And Concurrent Variable-interval Variable-ratio Schedules.

PMID- 16812895
TI  - Reversed effects in closed and open economies.

PMID- 16812894
TI  - Averaging Effects In The Study Of Fixed-ratio Response Patterns.

PMID- 16812896
TI  - Time, trace, memory.

PMID- 16812898
TI  - Molar And Molecular Control In Variable-interval And Variable-ratio Schedules.

PMID- 16812897
TI  - Human Sensitivity To Concurrent Schedules Of Reinforcement: Effects Of Observing
      Schedule-correlated Stimuli.

PMID- 16812899
TI  - The effects of differing response types and price manipulations on demand
      measures.

PMID- 16812900
TI  - Choice, contingency discrimination, and foraging theory.

PMID- 16812901
TI  - Some Effects Of Intertrial Interval Duration On Discrete-trial Choice.

PMID- 16812902
TI  - Equivalence relations between visual stimuli: the functional role of naming.

PMID- 16812903
TI  - Behavior Analysis And Signal-detection Theory.

PMID- 16812905
TI  - Pragmatism, Science, And Society: A Review Of Richard Rorty's Objectivity,
      Relativism, and Truth: Philosophical Papers, Volume 1.

PMID- 16812904
TI  - Stimuli, reinforcers, and behavior: an integration.

PMID- 16812907
TI  - Erratum.

PMID- 16812906
TI  - Stimulus Presentation Ratios And The Outcomes For Correct Responses In Signal
      detection Procedures.

PMID- 16812908
TI  - The man who listens to behavior: folk wisdom and behavior analysis from a real
      horse whisperer.

PMID- 16812909
TI  - The effects of number of sample stimuli and number of choices in a detection task
      on measures of discriminability.

PMID- 16812911
TI  - Pavlovian contingencies and resistance to change in a multiple schedule.

PMID- 16812910
TI  - Establishing Functional Classes In A Chimpanzee (Pan troglodytes) With A Two-item
      Sequential-Responding Procedure.

PMID- 16812912
TI  - Class-consistent Differential Reinforcement And Stimulus Class Formation In
      Pigeons.

PMID- 16812913
TI  - Instructions as discriminative stimuli.

PMID- 16812914
TI  - The transitivity of choices between different response requirements.

PMID- 16812915
TI  - The value of everyday examples in the teaching of learning: a comment prompted by
      machado and silva (1998).

PMID- 16812916
TI  - Reward Density And Variable-interval Schedule Performance In An Open Economy.

PMID- 16812917
TI  - Leaving patches: effects of economy, deprivation, and session duration.

PMID- 16812918
TI  - Within-session Analysis Of Visual Discrimination.

PMID- 16812920
TI  - A Review Of Geraldine Joncich's The Sane Positivist: A Biography Of Edward L.
      Thorndike.

PMID- 16812919
TI  - Thorndike's Legacy: Learning, Selection, And The Law Of Effect.

PMID- 16812922
TI  - After the puzzle boxes: thorndike in the 20th century.

PMID- 16812921
TI  - Thorndike's Puzzle Boxes And The Origins Of The Experimental Analysis Of
      Behavior.

PMID- 16812923
TI  - Analyzing Thorndike's Law Of Effect: The Question Of Stimulus-response Bonds.

PMID- 16812924
TI  - Edward L. Thorndike: the selectionist connectionist.

PMID- 16812925
TI  - Pavlov And Skinner: Two Lives In Science (An Introduction To B. F. Skinner's
      "Some Responses To The Stimulus 'Pavlov' ").

PMID- 16812926
TI  - Some responses to the stimulus "pavlov." (reprinted).

PMID- 16812927
TI  - Position of the American Dietetic Association: individual-, family-, school-, and
      community-based interventions for pediatric overweight.
AB  - The American Dietetic Association (ADA), recognizing that overweight is a
      significant problem for children and adolescents in the United States, takes the
      position that pediatric overweight intervention requires a combination of family
      based and school-based multi-component programs that include the promotion of
      physical activity, parent training/modeling, behavioral counseling, and nutrition
      education. Furthermore, although not yet evidence-based, community-based and
      environmental interventions are recommended as among the most feasible ways to
      support healthful lifestyles for the greatest numbers of children and their
      families. ADA supports the commitment of resources for programs, policy
      development, and research for the efficacious promotion of healthful eating
      habits and increased physical activity in all children and adolescents,
      regardless of weight status. This is the first position paper of ADA to be based
      on a rigorous systematic evidence-based analysis of the pediatric overweight
      literature on intervention programs. The research showed positive effects of two
      specific kinds of overweight interventions: a) multicomponent, family-based
      programs for children between the ages of 5 and 12 years, and b) multicomponent,
      school-based programs for adolescents. Multicomponent programs include behavioral
      counseling, promotion of physical activity, parent training/modeling, dietary
      counseling, and nutrition education. Analysis of the literature to date points to
      the need for further investigation of promising strategies not yet adequately
      evaluated. Furthermore, this review highlights the need for research to develop
      effective and innovative overweight prevention programs for various sectors of
      the population, including those of varying ethnicities, young children, and
      adolescents. To support and enhance the efficacy of family- and school-based
      weight interventions, community-wide interventions should be undertaken; few such
      interventions have been conducted and even fewer evaluated.

PMID- 16812928
TI  - American Dietetic Association: standards of practice and standards of
      professional performance for registered dietitians (generalist, specialty, and
      advanced) in oncology nutrition care.
AB  - The Standards of Practice and Standards of Professional Performance in Oncology
      Nutrition Care serve as a professional resource for self-evaluation and
      professional development for RDs specializing in oncology nutrition practice.
      Application of these documents in clinical practice presents the opportunity for
      quality improvement in oncology nutrition services provided by the RD. Just as
      the professional self-evaluation and continuing education process is an ongoing
      cycle, these standards are also a work in progress, and will be reviewed and
      updated on a regular basis. The Standards of Practice and Standards of
      Professional Performance are a quality initiative of the ADA and ON DPG that
      reflect a commitment to improving the quality of nutrition services provided by
      RDs in oncology settings.

PMID- 16812929
TI  - Epidemiology of WHO-confirmed human cases of avian influenza A(H5N1) infection.

PMID- 16812930
TI  - [A pregnant woman with acute renal failure].

PMID- 16812931
TI  - [Pregnant women with non-pregnancy related disease].

PMID- 16812933
TI  - [Successful HAART in Malawi].

PMID- 16812934
TI  - SPECT-CT imaging for earlier detection of breast cancer.

PMID- 16812935
TI  - Targeting early stage DCIS breast cancer directly in the ducts with intraductal
      chemotherapy.

PMID- 16812936
TI  - Surprising finding that low-fat diet may reduce risk of breast cancer but not
      colon cancer or heart disease.

PMID- 16812938
TI  - Devices and desires: gender, technology, and American nursing. [Review of:
      Sandelowski, M. Devices and desires: gender, technology, and American nursing.
      Chapel Hill: U. of North Carolina Pr.; New York: Hill and Wang, 2000].

PMID- 16812937
TI  - Molecular diagnostics of lymphoma: coming of age.

PMID- 16812939
TI  - All this hell: U.S. nurses imprisoned by the Japanese. [Review of: Monahan, E.M.
      and Neidel-Greenlee, R. All this hell: U.S. nurses imprisoned by the Japanese.
      Lexington: U. Pr. of Kentucky, 2000].

PMID- 16812940
TI  - Megestrol acetate for cancer anorexia/cachexia #100.

PMID- 16812941
TI  - Women in labor: mothers, medicine, and occupational health in the United States,
      1890-1980. [Review of: Hepler, A.L. Women in labor: mothers, medicine, and
      occupational health in the United States, 1890-1980. Columbus: Ohio State U. Pr.,
      2000].

PMID- 16812943
TI  - Permissible dose: a history of radiation protection in the twentieth century.
      [Review of: Walker, J.S. Permissible dose: a history of radiation protection in
      the twentieth century. Berkeley: U. of California Pr., 2000].

PMID- 16812942
TI  - Beauty and business: commerce, gender, and culture in modern America. [Review of:
      Scranton, P., ed. Beauty and business: commerce, gender, and culture in modern
      America. New York: Routledge, 2000].

PMID- 16812944
TI  - [Adjuvant therapy with trastuzumab in primary breast neoplasms--findings and
      validity of--opinion on the competence of the Central Oncology section of the
      North German Society].

PMID- 16812945
TI  - [Organ fibrosis: pathology as an occult presence].

PMID- 16812946
TI  - The politics of representation: doing and writing "interested" research on
      midwifery.

PMID- 16812947
TI  - Phlebotomy issues and quality improvement in results of laboratory testing.
AB  - Laboratory testing is an integral part of the decision-making process, and
      results of laboratory testing often strongly influence medical diagnoses and
      therapies. There is a long history of quality requirements in laboratory
      medicine, which have mainly concerned the analytic phase of this process. Owing
      to the substantial advances in technology, laboratory automation and analytic
      quality, there is increasing evidence that further quality improvements should be
      targeted to extra-analytic phases of laboratory testing. Objective difficulties
      to monitor most of the preanalytic variables which lie outside the direct control
      or supervision of the laboratory personnel, such as phlebotomy, call for
      effective educational and preventive policies. Owing to high personnel turnover
      rates, lack of understanding about good laboratory practices, and inadequate
      training, there are several opportunities for making errors during phlebotomy,
      which mainly concern patient misidentification and collection of unsuitable
      specimens for testing due to unsuited venous accesses, venous stasis,
      inappropriate collection devices and containers. Improved standardization of
      phlebotomy techniques, along with operative guidelines dissemination, continuous
      education, certification, and training of health care professionals involved in
      blood drawing responsibilities would enhance the chance of obtaining specimens of
      consistent quality, with favorable revenues for the health care system and the
      patient's outcome.

PMID- 16812948
TI  - Hypochromic microcytic anemia as a clinical presentation of celiac disease.
AB  - To determine the prevalence of celiac disease in patients with hypochromic
      microcytic anemia and to evaluate if and how celiac disease influenced the
      outcome of anemia, 207 women with hypochromic microcytic anemia were enrolled.
      Multivariate statistical analysis showed significant differences for the values
      of hemoglobin comparing the celiac group with the other groups. Comparison of the
      clinical complications showed an evident statistical significance. Our study
      showed that among patients with iron deficiency anemia there was a high
      prevalence of celiac disease. Delayed diagnosis can lead to long-term chronic
      anemia and various clinical complications. We therefore believe that an early
      diagnosis prevents and minimizes the complications related to celiac disease, and
      that serologic screening should become routine in the diagnostic protocol for
      hypochromic microcytic anemia.

PMID- 16812949
TI  - Cytochrome P-450 2D6 and 2C19 polymorphisms and length of hospitalization in
      psychiatry.
AB  - We evaluated whether cytochrome P450 (CYP) poor metabolizer polymorphisms of
      CYP2D6 and CYP2C19 are relevant for the outcome (measured by length of
      hospitalization) during treatment with psychotropic medications in patients with
      depression or schizophrenia. 229 patients were genotyped by real-time PCR
      hybridization probe melting curve technique for CYP2C19*2, CYP2D6*3, *4, and *6,
      respectively. The gene deletion CYP2D6*5 was analyzed by a long PCR method.
      Detailed clinical information was obtained from 53 subjects. Patients genotyped
      homozygous or heterozygous for those CYP2D6 and CYP2C19 poor metabolizer alleles
      were treated for a longer time in hospital (median 57.5 vs. 40.0 days).
      Psychiatric patients might benefit from CYP genotyping, the duration of stay as
      inpatient might be reduced by a priori selection of the appropriate drug for the
      individual patient.

PMID- 16812950
TI  - Length of erythrocyte sedimentation rate (ESR) adjusted for the hematocrit:
      reference values for the TEST 1 method.
AB  - It is known that the erythrocyte sedimentation rate is related to the erythrocyte
      concentration in blood. Recently, some authors have proposed a method for
      estimating the relation between the Westergren erythrocyte sedimentation rate and
      the erythrocyte sedimentation rate adjusted on an hematocrit of 0.35 L/L. In this
      study we firstly evaluated in 236 samples the relation between the erythrocyte
      sedimentation rate measured by the TEST 1 analyzer in samples corrected to 0.35
      L/L of hematocrit and the erythrocyte sedimentation rate measured in undiluted
      samples, and the hematocrit and the hemoglobin concentration, obtaining a
      multiple correlation coefficient of 0.956; (p < 0.001). Comparison between the
      corrected for HCT erythrocyte sedimentation rate, measured vs estimated, showed a
      bias of 0.0 (0.95 CI: -0.98 to 0.98 mm/h) with an agreement limit +/- 14.5 mm/h.
      Then, the reference intervals for the estimated erythrocyte sedimentation rate at
      0.35 L/L of hematocrit were calculated by means of an indirect method (Kairisto),
      using the one-year stored data (47810 results) in our laboratory database. Our
      data showed that the erythrocyte sedimentation rate corrected to 0.35 L/L of
      hematocrit could be estimated by a simple formula using the TEST 1 results; the
      reference ranges were higher than the reference ranges for uncorrected samples.
      New reference intervals were needed for an improved evaluation of the patients,
      and a table of reference intervals for age and sex is presented.

PMID- 16812951
TI  - Viral gastroenteritis and genetic characterization of recombinant norovirus
      circulating in Eastern Russia.
AB  - From November 2003 to March 2004 a total of 100 fecal specimens from infants and
      children with acute gastroenteritis in the city of Birobidzhan, Eastern Russia
      were tested for the presence of diarrheal viruses by RT-multiplex PCR. Of these,
      74 fecal specimens were positive for diarrheal viruses and this represented 74%.
      Among the diarrheal viruses detected, group A rotavirus was the most prevalent
      (67%; 67 of 100), followed by norovirus (4%; 4 of 100), group C rotavirus (1%, 1
      of 100), sapovirus (1%; 1 of 100), and hepatitis A virus (1%; 1 of 100). It was
      found that 86.6% (58 of 67) of group A rotavirus were serotyped as G3. Sapovirus
      and hepatitis A virus were genetically determined to belong to GI/1 and
      subgenotype 1A, respectively. Interestingly, all norovirus isolates in the study
      turned out to make a novel cluster when polymerase-based grouping was performed.
      It is noteworthy to point out that these norovirus isolates were further
      genetically characterized as naturally occurring recombinants, which were firstly
      found circulating in the Russian population studied. Breakpoint analysis of
      recombinant norovirus showed that the recombination site was at the open reading
      frame (ORF)1/ORF2 overlap. This is the first report of the existence of acute
      gastroenteritis caused by recombinant norovirus in Eastern Russia.

PMID- 16812952
TI  - Apoptosis-specific activation markers in on- versus off-pump coronary artery
      bypass graft (CABG) patients.
AB  - BACKGROUND: The relation of epithelial/endothelial apoptosis and secretion of
      death-inducing receptors (DIR) in comparison to vascular adhesion molecules is
      not known in patients undergoing the On- versus Off-pump coronary artery bypass
      graft (CABG) procedure. METHODS: 30 patients were prospectively included in the
      study (On- vs. Off-pump CABG, each n = 15). Serum samples were obtained prior to,
      and 30 minutes, 60 minutes and 24 hours after CABG operation. ELISA was utilized
      to detect caspase-cleaved cytokeratin-18 (CK18) by means of M30 antibody, soluble
      VCAM-1, soluble ICAM-1, and soluble DIR TNFR-1 and CD95. RESULTS: Soluble caspase
      cleaved CK18 was increased and leveled to initial values at 24 hrs. sICAM-1
      showed a significant decrease at 30 minutes and 60 minutes in comparison to
      preoperative values. sTNFR-1/sCD95 showed a rise that was not significant to
      preoperative values. CONCLUSION: These results indicate for the first time that
      epithelial/endothelial apoptosis is occurring in patients undergoing bypass
      operation, irrespective of the CABG procedure selected.

PMID- 16812953
TI  - Prevention of iatrogenic transmission of B19 infection: different approaches to
      detect, remove or inactivate virus contamination.
AB  - Parvovirus B19 is a frequent contaminant of human blood and plasma derivatives
      and iatrogenic transmission of B19 infection has been shown to occur through the
      administration of contaminated products. Manufacturing procedures, generally used
      for removal or inactivation of enveloped viruses (HIV, HCV and HBV) are not
      always effective in the elimination of B19 virus. A certain risk of contamination
      remains for some plasma derivatives due to the high-titer viral load in the
      starting blood donations and the extreme heat resistance and small size of the
      virus. This review provides an update on the different approaches currently
      available to detect, remove or inactivate B19 virus in order to enhance the
      safety margins of plasma products. Nucleic acid amplification techniques are the
      methods of choice for the detection of viruses, due to their high specificity and
      sensitivity. NAT assays are beneficial tools for the identification of
      contaminated mini-pools or plasma pools and the quantification of B19
      contamination. They may also be valuable for testing the removal of B19 virus
      during manufacturing: since the virus may not be completely inactivated or
      removed by chemical or physical treatments, residual B19 contamination should
      always be checked. Solvent-detergent treatments fail to destroy B19 capsids
      because of the absence of a lipid-envelope, and heat treatments (pasteurization
      and dry-heat methods) cannot guarantee a complete viral inactivation because of
      the variable heat sensitivity of the virus.

PMID- 16812954
TI  - Sports medicine: not "just for jocks" any more.

PMID- 16812955
TI  - Why we object to NAOMI. Heroin maintenance in Canada.

PMID- 16812956
TI  - Making the most of our time.

PMID- 16812957
TI  - Making the most of our time.

PMID- 16812958
TI  - Family medicine as a specialty.

PMID- 16812959
TI  - Family medicine as a specialty.

PMID- 16812960
TI  - Family medicine as a specialty.

PMID- 16812961
TI  - It is a privilege.

PMID- 16812962
TI  - Does vitamin K prophylaxis prevent bleeding in neonates exposed to enzyme
      inducing antiepileptic drugs in utero?
AB  - QUESTION: One of my epileptic patients takes carbamazepine. She is 36 weeks
      pregnant and has asked me whether she should start vitamin K to prevent neonatal
      bleeding. Does current evidence support this practice? ANSWER: Recent evidence
      does not support the notion that newborns of women treated with enzyme-inducing
      anticonvulsant drugs are at increased risk of hemorrhagic disease. Antenatal
      vitamin K can be prescribed on an individualized basis in certain circumstances,
      such as imminent premature delivery.

PMID- 16812963
TI  - Practice tips. Keep a purple book: record every detail of an elderly person's
      care.

PMID- 16812964
TI  - Approach to injuries in active people.
AB  - OBJECTIVE: To review the basic principles underlying treatment of injuries in
      active people. SOURCES OF INFORMATION: Basic science texts and reports of
      observational and randomized trials on treatment of musculoskeletal injuries were
      retrieved during previous exhaustive systematic reviews published by the author
      on a variety of musculoskeletal injury topics. MAIN MESSAGE: After an injury,
      further damage or re-injury can be prevented either by decreasing the stress on
      the tissue or increasing the stress the tissue can withstand. Regardless of the
      type of injury, clinicians should aim to restore function; aim to increase
      activity without increasing pain; recommend that patients start slowly and
      increase activity gradually; revisit diagnosis and treatment if patients are not
      responding; and treat the patient, not the condition. CONCLUSION: Most
      musculoskeletal injuries in the general population can be managed effectively by
      family physicians. Management should follow the basic principles of exercise
      training.

PMID- 16812965
TI  - Omega-3 fatty acids: their beneficial role in cardiovascular health.
AB  - OBJECTIVE: To examine evidence for the role of omega-3 fatty acids in
      cardiovascular disease. QUALITY OF EVIDENCE: PubMed was searched for articles on
      the role of omega-3 fatty acids in cardiovascular disease. Level I and II
      evidence indicates that omega-3 fatty acids are beneficial in improving
      cardiovascular outcomes. MAIN MESSAGE: Dietary intake of omega-3 fatty acids has
      declined by 80% during the last 100 years, while intake of omega-6 fatty acids
      has greatly increased. Omega-3 fatty acids are cardioprotective mainly due to
      beneficial effects on arrhythmias, atherosclerosis, inflammation, and thrombosis.
      There is also evidence that they improve endothelial function, lower blood
      pressure, and significantly lower triglycerides. CONCLUSION: There is good
      evidence in the literature that increasing intake of omega-3 fatty acids improves
      cardiac outcomes. Physicians need to integrate dietary recommendations for
      consumption of omega-3 fatty acids into their usual cardiovascular care.

PMID- 16812967
TI  - New guidelines for concussion management.

PMID- 16812966
TI  - Premenopausal women and low bone density.
AB  - OBJECTIVE: To review the evidence and provide an approach to management of low
      bone density among premenopausal women. QUALITY OF EVIDENCE MEDLINE: was searched
      from January 1990 to November 2004 and articles graded by level of evidence (I to
      III). Diagnosis and management recommendations were based on evidence from
      randomized controlled trials and expert consensus. MAIN MESSAGE: Bone mineral
      density (BMD) testing among premenopausal women should be completed only in the
      presence of approved indications. Current evidence does not support screening for
      osteoporosis among premenopausal women. Low BMD in premenopausal women is
      associated with a lower fracture risk than seen in postmenopausal women. In the
      absence of fragility fractures, low BMD might reflect low peak bone mass based on
      genetic predisposition, environment, and lifestyle factors. Clinical evaluation
      enables distinction between low peak bone mass and a systemic disorder resulting
      in low BMD and skeletal fragility. Common causes of low bone density among
      premenopausal women include ovulatory disturbances and low body weight.
      CONCLUSION: Bone mineral density alone is insufficient for diagnosis of
      osteoporosis among premenopausal women in the absence of fragility fractures.
      Antiresorptive therapy has been evaluated and shown to benefit premenopausal
      women using glucocorticoid therapy or those with primary hyperparathyroidism.

PMID- 16812968
TI  - Whom might you see if afflicted with a sports injury?

PMID- 16812969
TI  - Where have all the residents gone? Part 1: Putting the declining family medicine
      match rates into context.

PMID- 16812970
TI  - Focus on Cuba's accomplishments.

PMID- 16812972
TI  - [Abdominal myomectomy as an alternative to hysterectomy: analysis of 504 cases].
AB  - Surgical management of symptomatic uterine fibroids by abdominal myomectomy.
      MATERIAL AND METHODS: Authors review their experiences and surgical methods for
      504 abdominal myomectomies performed over the last 15 years. They retrospectively
      analyze the annual number of myomectomies, the age distribution, the most
      frequent indications, the location, size, and number of leiomyomas, the number of
      cases in which the uterine cavity was opened, the frequency of post-operative
      complications, and the number and outcome of post-myomectomy pregnancies.
      RESULTS: The annual number of myomectomies increased 26 times over the 15 year
      period, the average age at myomectomy was 33 years, 1.8% of post-fertile patients
      desired surgery which allowed for conservation of the uterus. The three most
      frequent indications for myomectomy were abdominal pain, infertility and
      menorrhagia. Regarding location, size and number; 82.7% of fibroids were
      submucosal/intramural and/or larger than 7 cm and/or greater than three in
      number. The uterine cavity was opened in 112 cases (22.2%). Post-operative
      complications occurred in 67 cases (13.3%): 7.7% required transfusions, 2.2%
      needed repeat laparotomy, two of which resulted in hysterectomy, and fever
      occurred in 13 cases (3.0%). There were 122 (24.2%) pregnancies in 105 patients
      following myomectomy. Eighty-nine patients conceived once, 15 patients conceived
      twice and 1 patient conceived three times post-myomectomy. There were 26
      spontaneous abortions representing 5.2% of the post-myomectomy patients and 21.3%
      of the conceived pregnancies. There were 96 deliveries in 19.0% of the patients
      who had myomectomy and 78.7% of the total conceived pregnancies. CONCLUSION:
      Authors suggest that abdominal myomectomy for the therapy of symptomatic uterine
      fibroids is an effective surgical alternative to hysterectomy one, which
      preserves fertility and femininity. In cases where the fibroids have well-defined
      borders, the success of surgery does not depend on the location, size or number
      of fibroids. In cases with adenomyosis, myomectomy alone is not sufficient to
      alleviate the symptoms. When the uterine cavity is opened during surgery, post
      operative transcervical drainage is suggested to prevent hematometra, post
      operative adhesions inside the uterus, infection, fever and wound dehiscence.

PMID- 16812971
TI  - [Cytogenetic and molecular monitoring of chronic myeloid leukemia].
AB  - The t(9;22) translocation, which results in a fusion protein with abnormal
      tyrosine-kinase activity, plays a central role in the pathogenesis of chronic
      myeloid leukemia. The selective inhibition of this chimeric protein with imatinib
      mesylate is an efficient therapeutic option, haematologic and cytogenetic
      responses can be achieved in most of the patients. The primary goal of monitoring
      the disease is to assess the efficiency of the therapy, to highlight those
      patients, whose survival may be improved by modifying treatment. Three methods
      are widely used for the genetic monitoring of chronic myeloid leukemia. With
      karyotyping, the proliferating bone marrow cells can be evaluated. The use of
      fluorescent in situ hybridization makes the cytogenetic analysis of each cell
      within the sample possible. Real-time quantitative polymerase chain reaction is
      capable of quantifying residual leukemia far below the sensitivity of
      cytogenetics. The results of these three methods have different biological
      meanings, thus, for the interpretation of the results, the knowledge of the
      characteristics, the benefits and the draw-backs of the methods is required. The
      present study shows the most important characteristics of these methods based on
      the literature and data acquired from 1165 samples of 197 patients detected by
      the authors.

PMID- 16812973
TI  - [The role of biological drugs in the treatment of psoriasis, results from 9
      randomized placebo-controlled trials].
AB  - BACKGROUND: Recognition the key role of TNF-alpha in the pathogenesis of
      psoriasis makes possible to use new and efficacious drugs in the treatment. In
      the years past more trials were published, which are examining the efficacy of
      different biological drugs. There is no analysis which is including all the
      trials with biological drugs. OBJECTIVE: The authors compared the efficacy of
      biological drugs - efalizumab, etanercept, infliximab - in the treatment of
      psoriasis. The evidences on effect of biological drugs were synthesized. The
      safety of drugs also was examined. METHODS: The authors searched the MEDLINE
      database for all trials with TNF-alpha in the treatment of psoriasis. The authors
      conducted a meta-analysis with the results of trials. The random effect model
      were used for the data synthesis, the results were probed with Mantel-Haenszel
      test. RESULTS: Data were combined from 13 trials included 4165 patients. All the
      three examined biological drugs are significantly superior to placebo treatment
      in improving the symptoms of psoriasis. Data from 3 trials included 1242 patients
      prove, that using 1 mg/kg etanercept the proportion of patients whom skin
      response improved at least 75% is greater with 25% than using placebo (RD = 0.25
      95% Cl 0.21-0.29). Data from 5 trials included 995 patients show, that using 2 x
      25 mg etanercept the proportion of patients whom skin response improved at least
      75% is greater with 29% than using placebo (RD = 0.29 95% Cl 0.24-0.33). Data
      from 5 trials included 759 patients prove, that using 5 mg/kg infliximab the
      proportion of patients whom skin response improved at least 75% is greater with
      73% than using placebo (RD = 0.73 95% Cl 0.68-0.78). Biological treatment of 3
      patients improves 1 patient's skin-symptoms at least with 75% (NNT = 2.7 95% Cl
      2.6-2.9). CONCLUSIONS: According to the available data the TNF-alpha inhibitors
      are effective in improving the symptoms of psoriasis non-responding to the
      conventional treatment. After the meta-analysis of data infliximab seems to be
      the most effective biological treatment.

PMID- 16812974
TI  - [Thoughts about the results of the "IDEAL" study].
AB  - INTRODUCTION: Evidences and guidelines suggest that more intensive lowering of
      LDL-cholesterol will provide further benefit in coronary artery disease. AIM AND
      METHOD: In the IDEAL study patients with previous myocardial infarction were
      randomly assigned to receive 80 mg of atorvastatin (n = 4439) or 20-40 mg
      simvastatin (n = 4449). The median follow-up was 4.8 years. The objective was to
      compare the effects of two strategies of lipid lowering therapy. RESULTS: During
      treatment mean LDL-cholesterol levels were 2.7 mmol/l in the simvastatin group
      and 2.1 mmol/l in the atorvastatin group. A major coronary event occurred in 463
      (10.4%) simvastatin patients and in 411 (9.3%) atorvastatin patients (p = 0.07).
      Death from any cause occurred 374 (8.4%) in the simvastatin group and 366 (8.2%)
      in the atorvastatin group (p = 0.81). Nonfatal acute myocardial infarction
      occurred 321 (7.2%) and 267 (6.0%) in the two groups (p = 0.02). Patients in the
      atorvastatin group had higher rates of drug discontinuation due to non-serious
      adverse events; transaminase elevation resulted in 43 (1.0%) versus 5 (0.1%)
      withdrawals (p <0.001). CONCLUSION: Patients with high risk or very high risk may
      benefit from intensive lowering of LDL-cholesterol without an increase of adverse
      reaction but try to find the ideal statin and dose of statin.

PMID- 16812975
TI  - [Phosphor/sulphur ratio: indicator of malignant uterine changes].
AB  - The purpose of the present study was to find a correlation between gynaecological
      diseases--myoma (26), adenocarcinoma uteri (21) - and P/S (phosphor/sulphur)
      ratios of different regions of uterus. Routine histological specimens were re
      examined with the intention to select representative regions of the uteruses for
      element analysis. Conventional haematoxylineosin stained sections were used to
      identify histological alterations by light microscopy. Energy-dispersive
      spectroscopic (EDS) investigations were carried out to analyse the morphology and
      the related element composition of the samples. The results of the non-parametric
      statistical test (Wilcoxon two-sample test) indicate that the P/S ratios were
      significantly higher in adenocarcinoma (0.8891 +/- 0.0757) than in myoma (0.4713
      +/- 0.0306). P/S ratio of different pathologic regions of uteruses seems worth
      examining in a larger study population.

PMID- 16812976
TI  - [Haemochromatosis].

PMID- 16812977
TI  - Congenital short QT syndrome. A review.
AB  - Sudden cardiac death in individuals with structurally normal hearts accounts for
      approximately 20% of sudden cardiac death cases. Patients in this subgroup suffer
      from what has been named "electrical diseases" which are gradually coming into
      focus as inherited ion channelopathies, diseases of anchoring proteins or of
      intracellular calcium regulating proteins. From 1993, the Short QT Syndrome
      (SQTS) came to our attention, as a new inherited "electrical disease" associated
      with increased risk of sudden cardiac death and atrial fibrillation. Mutations of
      Ikr, Iks, Ikl channels cause dysfunctional Iks, Ikr, Ikl channels with an
      increase in the net outward K current leading to shortening of repolarization.
      This in turn leads to a shorter QT interval on the ECG and shorter atrial and
      ventricular refractory periods with increased susceptibility to VF and AF. There
      seems to be an autosomal dominant mode of inheritance. The clinical profile of
      SQTS consists of: family history of sudden cardiac death, personal history of
      palpitations, syncope, dizziness, resuscitated SCD, history of AF and documented
      VF. It is important to emphasize that SQTS is symptomatic from early age (new
      born) to old age. Therefore, it is possible that SQTS accounts for some of the
      sudden infant death syndrome cases and for some cases of AF, especially lone AF.
      The only efficient treatment for ventricular arrhythmias is ICD, associated with
      drugs (Quinidine or Propaphenone) for AF prophylaxis and for reducing the number
      of ventricular arrhythmic events (and ICD discharges).

PMID- 16812978
TI  - Clinical impact of cachexia on survival and outcome of cancer patients.
AB  - Approximately one half of all cancer patients experience a complex metabolic
      status involving progressive exhaustion of adipose and skeletal muscle tissue.
      This condition, known as cachexia, is responsible for more than 20% of the
      overall deaths in cancer patients. Although its main mechanisms remain unknown,
      several hypotheses have been proposed. One of the pathogenic mechanisms involves
      leptin and hypothalamic neuropeptide-containing pathways. Orexigenic and
      anorexigenic neuropeptides are down-regulated respectively upregulated as a
      result of cancer. Other pathogenic theories consider tumour derived factors, such
      as LMF (Lipid Mobilising Factor) and PIF (Proteolysis-inducing Factor), to be
      responsible for the weight losing pattern of cancer patients via activation of
      various catabolic pathways (e.g. ubiquitin-proteasome proteolytic-pathway, etc.).
      Despite the controversial discussion of cachexia-inducing mechanisms it is clear
      that proinflammatory cytokines, such as TNFalpha, IFNgamma, IL-1, IL-6 and IL-8,
      are linked to all pathways that induce cachexia. Although only limited treatment
      exists for patients with cancer cachexia, recent studies with eicosapaentanoic
      acid showed promising effects in reversing weight losing pattern of cachectic
      patients. Cytokine targeted monoclonal antibodies, cytokine traps and genetic
      therapies are also evaluated for future therapeutic strategies.

PMID- 16812979
TI  - Dual renin angiotensin system blockade in patients with acute myocardial
      infarction and preserved left ventricular systolic function.
AB  - The activation of the renin-angiotensin system (RAS) is a major determinant of
      ventricular remodeling. We prospectively assessed whether the dual RAS blockade
      (angiotensin II AT 1-receptor blocker and angiotensin-converting enzyme inhibitor
      therapy) in patients with acute myocardial infarction (AMI) who were treated by
      primary percutaneous coronary intervention (PCI) and stenting provides benefit on
      the improvement of the left ventricle function. A secondary aim is to demonstrate
      that triple therapy with angiotensin-converting enzyme (ACE) inhibitors,
      angiotensin II AT 1-receptor blockers (ARBs) and beta blockers does not increase
      cardiovascular morbidity, cardiovascular mortality and all cause mortality.
      METHODS: We investigated 44 patients with AMI with ST elevation undergoing
      primary PCI and stenting. All patients received standard therapy including an ACE
      inhibitor and a beta blocker. We divided the patients into two groups, A and B.
      Valsartan was added to the standard therapy within the first 6 hours from the
      onset of AMI in group A. We assessed cardiovascular and all cause mortality,
      incidence of major acute coronary events (MACE), incidence of non-fatal AMI, the
      evolution of left ventricle ejection fraction (LVEF), wall motion score index
      (WMSI) and left ventricle end-systolic and end-diastolic diameters. The follow-up
      period was one year. RESULTS: There were no statistically significant differences
      between groups regarding cardiovascular and all cause mortality, incidence of
      MACE, incidence of non-fatal MI. LVEF significantly increased at 1 year in both
      groups. In both groups the reduction of end-systolic and end-diastolic diameters
      at 1 year was statistically significant. Echocardiographic findings demonstrated
      also a significant decrease of WMSI at 1 year in both groups. CONCLUSIONS: The
      dual renin-angiotensin system blockade (ARBs and ACE inhibitor) has proved its
      beneficial effect on the improvement of left ventricular function, without
      increasing cardiovascular mortality and incidence of non fatal myocardial
      infarction (MI) in patients with AMI treated by primary PCI and stenting within a
      1 year follow-up period.

PMID- 16812980
TI  - Is interleukin-18 correlated with endothelial dysfunction and platelet activation
      in patients with unstable angina?
AB  - The aim of the study was to assess the interaction between interleukin-18 (IL-18,
      a cytokine with a central role in the inflammatory cascade) and the presence of
      endothelial dysfunction and prothrombotic profile in patients with unstable
      angina and proven coronary artery disease. MATERIAL AND METHODS: The study EDIT
      ACS (Endothelial Dysfunction, Inflammation and Thrombosis in Acute Coronary
      Syndromes) was set in the Cardiology Department of our Institute, and inclusions
      were performed between June-November 2004. We included 40 consecutive patients
      with unstable angina hospitalized in our Department (mean age = 60.2 +/- 8.8
      years, 57.5% male), as well as 20 normal pts as a control population,matched for
      age and sex (mean age = 61.9 +/- 8.6 years, 58.3% male). All pts had the
      following biological studies performed: interleukin-18 (IL-18), C-reactive
      protein (CRP), fibrinogen, leukocyte count, and Von Willebrand factor, as well as
      platelet activity parameters (mean platelet volume, MPV and platelet distribution
      width, PDW). All pts had echographic studies of flow mediated dilatation (FMD)
      and measurement of carotid intima-media thickness (C-IMT), and underwent coronary
      angiography as well. RESULTS: We found that patients in the highest quartile of
      IL-18 had higher levels of CRP (11.9 +/- 4.2 vs 6.8 +/- 3.4 mg/l, p<0.01), von
      Willebrand factor (166% vs 150%, p=0.08), PDW (14.5 vs 13.2, p=0.04), MPV (11.2
      vs 10.2, p=0.02), as well as a higher number of coronary stenoses (mean no. of
      affected vessels 2.5 vs 1.1, p<0.001), trend towards higher carotid IMT (0.92 mm
      vs 0.81 mm, p=0.06). They also have significant endothelial dysfunction (FMD of 5
      % vs 8.5% for 4th quartile and 1st quartile respectively). Pts with higher levels
      of IL-18 associated a worse short term (in hospital prognosis) with 60% of pts in
      the 4th quartile having adverse events, versus 22% in the lowest quartile.
      CONCLUSIONS: High levels of interkleukin-18 are associated with endothelial
      dysfunction (high von Willebrand factor and low brachial FMD) and platelet
      activation (high MPV and PDW values), in pts with a higher number of affected
      coronary arteries but similar global atherosclerotic burden. This could explain
      the association between high levels of IL-18 and worse short-term prognosis in
      pts with unstable angina.

PMID- 16812981
TI  - Is age correlated with dynamic atrial decremental conduction properties?
AB  - Atrial fibrillation (AF) has been associated with premature beats and decreased
      atrial conduction velocities. On the other hand, prevalence of AF is increased in
      the elderly. The aim is to evaluate and analyze the relation between age, atrial
      size and a new index of dynamic interatrial conduction time (iaCT) in a
      homogeneous population of patients (pts) with structurally normal heart without
      AF. METHODS: 45 patients (pts) without structural heart disease aged 53 +/- 20
      years referred for electrophysiologic study were analyzed. To examine the atrial
      electrophysiologic characteristics we studied interatrial conduction time (iaCT),
      double potentials and fragmented atrial activity during premature stimulation of
      high right atrium; prior to investigation, all antiarrhythmic drugs were
      withdrawn for an appropriate period of time. The following parameters were
      assessed: baseline iaCT (iaCTb) between high right atrium (HRA) and distal
      coronary sinus (CS), iaCT during HRA pacing S1S1 600ms (iaCTS1), maximum
      prolongation of iaCT during S2 and S3 delivery (iaCTS2, iaCTS3). We calculated a
      derived parameter: maximum prolongation iaCT/decremental index (DI)= iaCT S3-ia
      CTS1/iaCTS1%. The following echocardiograhic parameters were assessed: left
      atrial dimensions and surface (LAs), right atrial dimension and surface (RAs),
      total atrial surface (TAs=LAs+RAs) and left atrial volume (LAv) calculated using
      ellipse formula. RESULTS: iaCT ranged from 42 to 87ms; DI ranged from 16 to 52%.
      Simple regression analysis demonstrated a statistically significant linear
      correlation between the age of pts and HRA DI (r = 0.76, r2 = 0.55, p <0.0001). A
      trend toward a significant correlation was found between TAs and DI (r=0.64,
      r2=0.41, p<0.0001) LAv and DI (r=0.59, r2=0.35, p<0.0001). No significant
      correlation was found in this group between age and iaCT. Atrial double
      potentials and fragmentated electrograms were recorded using HRA stimulation in
      CS leads in 7 pts (15%) all aged >35 years. Pts were divided into two groups: 17
      pts with normal electrophysiologic findings and 28 pts with junctional reentrant
      tachycardia. There were no significant differences between subgroups concerning
      the main studied parameters. CONCLUSIONS: This study shows a direct better
      correlation for age than atrial size in the relation with the dynamic behaviour
      interatrial conduction, suggesting that higher incidence in AF in the elderly
      might be also a consequence of the higher incidence of atrial conduction
      disturbances.

PMID- 16812982
TI  - Current developments in interventional treatment of total terminal aortic
      occlusions--laser, stenting and balloon angioplasty: experience of cardiology
      clinic of Targu-Mures.
AB  - The importance of interventional procedures in the complex treatment of
      peripheral arterial diseases is continuously increasing. In the current practice
      of our clinic, association of balloon angioplasty, laser angioplasty and arterial
      stenting in reconstruction of iliac arteries led to superior results in the
      latest years, these methods 11:42 PM 11:42 PM 11:42 PM being proved as an
      alternative to surgical interventions. In this article, we present several cases
      in which current indications for laser angioplasty were extended to target
      occlusions located in the terminal abdominal aorta. METHODS: 106 consecutive
      primary iliac interventions were performed on 88 patients with iliac or
      aortoiliac obstructive diseases, in the period September 2001 - October 2005, at
      the University of Medicine and Pharmacy of Targu-Mures, Romania, Clinic of
      Cardiology. Five of these patients (4 males, 1 female) presented occlusions of
      terminal aorta, in whom interventional treatment (peripheral transluminal
      angioplasty, laser angioplasty and stenting) was performed. Three cases presented
      total occlusion of terminal aorta, without any visualization of iliac arteries,
      and 2 cases presented occlusion of one aortoiliac axis, starting from terminal
      aorta. RESULTS: In all cases, complete repermeabilisation of aortoiliac axes was
      achieved, without complications. In all patients we recorded a significant
      improvement of symptomatology, and arterial Doppler showed an increase of Doppler
      ankle/brachial index in average from 0.4 up to 0.95. No complications have been
      recorded so far. CONCLUSION: Extension of classical indications of interventional
      treatment for balloon and laser angioplasty to occlusions located in terminal
      aorta is possible when the procedure is performed by an experienced team.
      Interventional techniques, having a superior applicability in practice, good
      results, low complication rates, and decreasing the hospitalization times, could
      be applied in the future to a larger extent, targeting also aortic occlusions.

PMID- 16812983
TI  - Interventional treatment with autoexpandable stents in iliofemoral arterial
      diseases.
AB  - The importance of peripheral arterial diseases is revealed by statistical data,
      which showed a frequency of arterial diseases equal to the one of stable angina
      Traditional treatment of these patients was the surgical bypass, but an
      alternative therapy in these cases is the interventional treatment. Arguments for
      this option could be: it is less expensive, it decreases the hospitalization
      time, it does not require general anesthesia, and complications are less frequent
      and less severe. Interventional treatment is recommended especially in cases of
      short, isolated lesions of great vessels. During the last years, indications for
      interventional treatment were expanded to more difficult and complex cases, due
      to the advances in technology of endoluminal treatment products and the recently
      introduced laser angioplasty technology. MATERIAL AND METHOD: Among the
      interventional techniques we apply in our clinic, we mention: percutaneous
      transluminal angioplasty, intraarterial stent implantation, laser angioplasty and
      intraarterial thrombolysis, some of them peformed with IVUS control. In a period
      of 14 years we examined a total number of 6,532 patients suffering from
      peripheral arterial obstructive diseases. In the past 3 years, in our new
      laboratory of interventional cardiology, new procedures have been introduced in
      the algorithm of interventional treatment, such as laser angioplasty. Invasive
      diagnosis performed in the Cardiology Clinic consisted in aortography in 746
      cases and peripheral arteriography in 2035 cases. Interventional treatment
      consisted in percutaneous transluminal angioplasty (1.240 procedures, 756
      performed in the latest 3 years), intraarterial thrombolysis (214 procedures),
      laser angioplasty (since June 2002-130 procedures performed) and stent implant
      (since 2001-61 cases). Axillar approach was also introduced in 2001 and was
      applied in 23% of cases. RESULTS: We recorded a 76.5% success rate using only PTA
      for repermeabilisation of the lower limb arteries. Association of intraarterial
      thrombolysis increased the success rate to 91%. Using laser angioplasty and
      autoexpandable stent implantation, the success rate achieved was 100%.
      CONCLUSION: Interventional treatment is an important alternative in the complex
      algorithm of treatment in PAOB. Intraarterial stenting significantly improves the
      immediate and the long term results of interventional treatment, and
      autoexpandable stents with thermal memory show superior results. Laser
      angioplasty is an adjuvant method which significantly improves the results of
      interventional treatment. In all these methods, a very important role plays the
      good cooperation of the team formed by cardiologist, angiologist and vascular
      surgeon.

PMID- 16812984
TI  - Cerebral ischemic attack secondary to hepatitis C virus infection.
AB  - Hepatitis virus C (HCV) is worldwide a health problem, which may lead to serious
      complications. The aim of this study was to correlate the onset of the cerebral
      ischemic attack accompanied by mixed cryoglobulinemia, with the chronic hepatitis
      C virus infection. These studies were carried out in 12 patients with
      serologic/virusologic confirmed chronic HCV infection associated with ischemic
      stroke. Ischemic stroke occurred in equal proportion in women and men. The
      patients did not know of HCV infection diagnosis at that moment. All patients had
      type II mixed monoclonal cryoglobulinemia, hypergammaglobulinemia with polyclonal
      IgG and monoclonal IgM, blood hyperviscosity, high level of cryocrit, positive
      rheumatoid factor, normal levels of serum transaminases, negative serum hepatitis
      B surface antigen (HBs Ag), negative anti HBc antibodies, positive HCV
      antibodies, positive serum RNA HCV, decreased serum C3 and C4 levels, antinuclear
      antibodies-false positive. Immunological tests for autoantibodies, namely, anti
      Sm antibody, anti-RNP antibody, anti-SS-A and -B antibodies, and anti-Scl
      antibody were not detectable due to high level serum cryoglobulin. Cryoglobulin
      was washed several times with an isotonic chloride solution for purification,
      then subject to immunological analyses. The purified cryoglobulin contained
      monoclonal IgM-kappa, polyclonal IgG. Cryoglobulinemia is a risk factor for
      ischemic stroke, as it causes arterial thrombosis.

PMID- 16812985
TI  - A comparative oxidative stress study--obesity with and without diabetes mellitus.
AB  - Oxidative stress and inflammation are involved in the initiation and progression
      of obesity and diabetes mellitus. The aim of our study was to find out some
      markers of oxidative stress in twenty obese patients with type 2 diabetes
      mellitus (group D) and twenty age-matched obese subjects (group O) and compare
      the results with the control values from twenty matched healthiy subjects (group
      H). Spectrophotometric methods were used. For the following plasma parameters:
      ceruloplasmin, d-ROM (determinable Reactive Oxygen Metabolites), alpha
      dicarbonyls, the values were modified in the same way for the groups of patients
      versus healthy subjects. The patients had higher alpha-dicarbonyls levels than
      the controls (for D versus H, p<0.047 and for O versus H, p<0.043). There were
      not significant differences for plasma ceruloplasmin and d-ROM levels. Comparing
      group O versus D, all the above parameters had very close values. The antioxidant
      capacity (AC) was higher in group O versus group H (p<0.001) and higher in group
      O versus D (p<0.02). The high AC for obese patients may be due to hyperuricemia.
      A negative correlation between AC and d-ROM concentrations and a positive
      correlation between ceruloplasmin and AC levels was observed for group D. Our
      data underline that in type 2 diabetes mellitus and obesity, the plasma markers
      of oxidative stress are modified in the same way. Oxidative stress may be a
      "connector" between these two diseases. Probably body fat reduction (for obese
      individuals) diminishes oxidant formation and, in its turn, the incidence of
      obesity related diseases, such as diabetes mellitus.

PMID- 16812986
TI  - Chemokines--their involvement in pathology.
AB  - Chemokines have a major role both in the immune inflammatory reactions and in the
      viral infection. The chemokines initiate the chemotactic migration of the
      leukocytes, with a role to play in the angiogenesis, in the collagen production
      and proliferation of the hematopoietic precursors as well.

PMID- 16812987
TI  - [Dr. Mihailo Petrovic--the first surgeon who studied in Serbia].

PMID- 16812988
TI  - The radial artery for coronary artery bypass grafting.
AB  - Coronary artery bypass grafting (CABG) is the standard surgical procedure for the
      treatment of advanced coronary artery disease. CABG surgery has been demonstrated
      to improve symptoms and, in specific subgroups of patients, to prolong life.
      Despite its success, the long-term outcome of coronary bypass surgery is strongly
      influenced by the fate of the vascular conduits used. Previous long-term studies
      have shown unsatisfactory patency of saphenous vein grafts used for myocardial
      revascularisation, compared with internal mammary artery grafts. Recently, the
      use of radial artery for CABG has enjoyed a revival, on the basis of the belief
      that it will help improving long-term results of coronary operations. The recent
      reports of encouraging mid-term and long-term patency rates of the radial artery,
      supports its continued use as a bypass conduit. In this paper, we review the
      current knowledge about the radial artery as a bypass graft, with special
      emphasis on the clinical results.

PMID- 16812989
TI  - The significance of lymphonodal micrometastasis in the patients with gastric
      adenocarcinoma.
AB  - Micrometastasis is defined as microscopical deposit of malignant cells, less than
      2mm in diameter, separated from the primary tumor. This does not include
      discontinous growth in peritumoral region, but include microinolvement of
      regional lymph nodes. The literature on micrometastases, with special resperct to
      nodal micrometastasis, and their implications in gastric adenocarcinoma have been
      reviewed. Immunohistochemical detection offer the best accuracy for detection of
      nodal micrometastasis. Molecular techniques are more sensitive than method of
      immunohistochemical detection, but methods are compromised with false positive
      results caused by various sources of biological contamination. It is more than
      obvious that there is no definite agreement neither about risk factors, nor
      definitive clinical significance of micrometastatic node involvement in the
      patients with gastric adenocarcinoma. At present, the role of occult lymph node
      involvement proved its significance in two major fields: defining criteria for
      limited surgical dissection in the patients with early (sm) carcinoma in respect
      to detection of micrometastatic tissue in sentinel lymph node, and distinguishing
      the category of pN0 (Mi+) patients with potential benefit of postoperative
      adjuvant therapy.

PMID- 16812990
TI  - [Selection and perioperative management of patients undergoing an orthotopic
      ileal bladder substitution].
AB  - Orthotopic ileal bladder substitution (Studer pouch) has gained much popularity
      during the last decade, offering the best form of urinary diversion in
      appropriately selected patients. The superiority of this procedure is well known,
      with a low complication and high success rate. In the present study the most
      important details in patient selection, surgical technique, perioperative
      management with short- and long-term postoperative follow-up are described.
      Adequate preoperative assessment results in a proper indication for surgery and
      appropriate patient selection. The cystectomy should be performed with atraumatic
      dissection and preservation of the urethral autonomic innervation and sphincter
      apparatus. The bladder substitute is constructed from a terminal ileal segment of
      proper length formed into a spherical shape. Implantation of the ureters into the
      reservoir should not be performed using an anti- reflux technique to avoid a high
      stricture rate. Anastomosis of the bladder substitute to the urethra must be flat
      and wide open, avoiding a funnel-shaped outlet. In the immediate postoperative
      period, careful monitoring is necessary to minimize metabolic complications of
      acidosis and salt loss. To achieve successful voiding rehabilitation, with
      complete reservoir emptying, good functional reservoir capacity and satisfactory
      continence, it is necessary to educate the patients as to the physiological
      functioning of the bladder substitute. Careful lifelong follow up is essential
      for the successful outcome. Respecting strict patient selection criteria and
      proper surgical technique are of utmost importance for the successful outcome of
      the procedure, but only if combined with regular follow-up.

PMID- 16812991
TI  - [Colonization of cental venous catheter in the Intensive Care Units at the
      Institute of Cardiovascular Disease "Dedinje"--one year study].
AB  - OBJECTIVES: The application of Central Venous Catheters (CVC) is associated with
      increased risk of microbial colonization and infection. The aim of present study
      was to assess the frequency of pathogens colonizing CVC and to determine their
      susceptibility pattern to various antimicrobial agents. MATERIALS AND METHODS: A
      total of 253 samples of CVC from intensive care units (ICU) patients were
      received for culture during 2003. All microorganisms were identified by standard
      microbiological methods and the susceptibility to antimicrobial agents was
      determined according to NCCLS recommendations. RESULTS: A total of 184 (72.7%)
      cultures were positive and 223 pathogens were isolated. Coagulase negative
      staphylococci (CNS) were the dominant isolates (24.7%), followed by Enterobacter
      spp. (12.1%), Pseudomonas spp. (11.7%), Enterococcus spp. (9.9%), Klebsiella spp.
      (8.6%), Candida spp. (7.6%), Acinetobacter spp. (7.6%), other Gram negative
      nonfermentative bacilli (5.8%), Serratia spp. (4.5%), Staphylococcus aureus
      (2.6%), Proteus mirabilis (2.2%), E. coli (1.8%) and Citrobacter spp. (0.9%).
      Meropenem (84.5%) and vancomycin (100%) remain the most effective antimicrobial
      agents against Gram negative and Gram positive bacteria, respectively.
      CONCLUSION: Gram negative bacilli and CNS are the commonest microorganisms
      colonizing CVC from ICU patients. The increasing resistance of the bacteria to
      antimicrobial agents is the major problem in spite of restricted policy of using
      antimicrobial agents in ICU.

PMID- 16812992
TI  - Axillary recurrence after modified radical mastectomy.
AB  - Optimal management for axillary recurrence is poorly understood. The aim of this
      study was to evaluate the risk factors for overall survival in the patients with
      axillary recurrence. Data of 1098 patients were collected from breast cancer
      registers from Clinic for Oncology Nis between 1990-1995. All patients underwent
      modified radical mastectomy. Axillary recurence was diganosed in 43 (3.92%)
      patients. Most patients were presented with a localized, palpable axillary mass
      30 (69.77%). Cox multivariate analysis of prognostic factors for breast cancer
      specific survival showed that node status HR 4.69 (1.50 to 14.72), tumor size HR
      3.18 (0.90 to 11.26) and axillary radiotherapy HR 1.99 (0.69 to 5.75) had
      statistically significant effect on breast cancer mortality. Log-rank (54.21 p <
      0.001) analysis showed significant difference for overall survival among women
      with a axillary recurrence based on different cancer stages. Tumor size and node
      status were the most important prognostic factors in women with axillary
      recurrence.

PMID- 16812993
TI  - [Off-pump myocardial revascularization (OPCAB) in patients with post-infarction
      unstabile angina, low ejection fraction and renal disfunction].
AB  - The purpose of this study is to present our experience in off-pump myocardial
      revascularization in patients with post-infarction unstable angina, left
      ventricular low ejection fraction and renal dysfunction. MATERIAL AND METHODS:
      From January 1998. until march 2002, at the Institute for Cardiovascular Diseases
      in Clinical Centre of Serbia, we have operated 20 patients with post infarction
      unstable angina, echocardiographicaly proved low ejection fraction (less than
      30%) and renal dysfunction (Serum Creatinin 150 micrograms per liter) using this
      method. All patients were male and they were between 52 and 79 years old.
      Preoperative characteristics, surgical treatment and postoperative course are
      presented. RESULTS: There was no hospital mortality, as well as important
      morbidity. There was no worsening of the renal and myocardial function.
      Postoperative ICU stay was from 1 to 2 days. Postoperative hospital stay was
      between 3 and 7 days. CONCLUSION: Off-pump myocardial revascularization is safe
      and effective procedure in all patients with left ventricular low ejection
      fraction and renal dysfunction.

PMID- 16812995
TI  - [A new approach to wound care in vaginal and surgical delivery].

PMID- 16812994
TI  - [Early results in the surgical treatment of Crawford type IV thoracoabdominal
      aneurysms].
AB  - OBJECTIVE: The aim of the study was to present the outcome of surgical treatment
      of patients with thoracoabdominal aortic aneurysm Crawford type IV, operated on
      between January 2001 and April 2004. METHODS: This study included 42 subsequent
      patients (40 males, 2 females, age 41-76 years). All patients underwent
      ultrasonography, angiography, computed tomography or magnetic resonance imaging
      (MRI). Surgical treatment was performed under combined anaesthesia (continuous
      thoracic epidural analgesia and general endotracheal anaesthesia). In two
      patients thoracophrenolumbotomy was performed at the level of X rib, while others
      were operated through left lumbotomy after the extra pleural resection of XI rib.
      We did not perform any spinal cord protection procedures in this type of
      aneurysm. Reconstruction included interposition of Dacron graft in 20 patients,
      aortobiiliac bypass in 18, and aortobifemoral bypass in 4 patients with different
      varieties of visceral branches reimplantation. RESULTS: Thirty-days mortality was
      31% (13 patients, two of them intraoperatively). Causes of death were: pulmonary
      embolism--in 1 patient; haemorrhage--in 2; myocardial infarction--in 4 (two
      intraoperative); acute renal failure--in 2; multisystem organ failure (MSOF)--in
      4 patients. Respiratory failure dominated in all cases of MSOF. One patient with
      acute renal failure had paraplegia also, and that was the only case of
      neurological complication in whole group. All female patients (2), all patients
      with ruptured aneurysm (4), acute myocardial infarction (4) and acute renal
      failure (2) have died. Advanced age (over 70 years) and the need for extensive
      operative procedure with bifurcated graft use significantly influenced their
      mortality (p < 0.01 and p < 0.05 respectively). CONCLUSIONS: Surgical treatment
      of thoracoabdominal aortic aneurysm Crawford IV type was successful in 69% of our
      patients. There was no need for spinal cord protection measures, and extra
      peritoneal approach with XI rib resection under the combined anaesthesia was
      preferred.

PMID- 16812996
TI  - [Variations in the surgical treatment of maxillary sinusitis].
AB  - From September 2001. to February 2004. in the Institute for ENT and Maxillofacial
      Surgery were investigated 107 patients with the inflammatory diseases of the
      maxillary sinuses. Patients with sinusitis were separated into group of patients
      with rhinogenic (72) and patients with odontogenic maxillary sinusitis (35). We
      found that the etiology of odontogenic sinusitis was mostly artificial caused
      after some dental surgery (88%), what is totally opposite to the spontaneous
      etiology of rhinogenic sinusitis. Surgical treatment of rhinogenic sinusitis
      mostly was endonasal polypectomy with operation by Caldwell-Luc or FESS.
      Odontogenic sinusitises were mostly treated by FESS and surgical "closing" of
      oral-antral fistula by local mucogingival flap (51%).

PMID- 16812997
TI  - [Effect of classic abdominal and vaginal hysterectomy on lower urinary tract
      function].

PMID- 16812998
TI  - New viewpoint to histological classification of malignant epithelial tumours of
      nasopharynx.
AB  - Malignant tumors of nasopharyngeal epithelium differ clinically depending on the
      course of disease and applied therapy. They are presented in regard to the sex,
      age, smoking habits, alcohol usage and nutrition factors. Various studies already
      showed various etiological-causal links with Epstein-Barr virus (EBV). This leads
      to diversity of various morphological and histological types of diseases
      belonging to various classifications. In this work we presented 60 diagnosed and
      treated cases with malignant tumor of nasopharyngeal epithelium in the Institute
      for Otorynolaringology and maxillofacial surgery of Clinical Center of Serbia.
      All of them were pato-histologicaly examined and 24 of them received serological
      examination in regard to the concept of association between malignant epithelial
      tumour and EBV. An important correlation between histopathology and serology was
      found. Finally, the terminology used by WHO classification is not optimal for
      further histological determination of nasopharyngeal malignancy; therefore we
      recommend the French classification of C. Micheaua.

PMID- 16812999
TI  - [Diet in bladder cancer ethiopathogenesis].
AB  - The aim of this paper is to show influence of different foods on bladder cancer
      appearance, as well as possible consequent ways of prevention. Consuption of food
      rich in animal fat and cholesterol, fried foods, especially several times used
      cookin oil for frying, processed meat with additives (nitrates, nitrites, azo
      colourrs) can influence bladder cancer occurrence. Regularly, continous
      consumption of fermented milk products, which contains come types of milky--acids
      bacterias, is considered as protective factor in developing bladder cancer.
      Reports that fruit and vegetable are protective food items are pretty consistent.
      Data about mineral intake and bladder cancer are obscure.

PMID- 16813000
TI  - [Predictive factors for recurrent haemorrhagies in patients with brain
      cavernoma].
AB  - Haemorrhage is most important sequelae of brain cavernoma, so the surgical
      treatment is very important for treatment that complication. There are two types
      of bleeding chronic subclinical microhaemorrhage and acute real haemorrhage.
      Pathophysiological factors wich are responsible for bleeding are not still
      understanding. The reason for this study is understanding of clinical curse of
      cavernomas and identification of factors of influence. This is retrospective and
      prospective study. We analised 36 patients with simpthomatic brain cavernoma,
      surgicaly treated in Institute of neurosurgery KCS in 10 years period (1987
      1997). Female were dominant but without statistical significance (p > 0.05). Male
      patients were older (32,1:29,8), but without statistical significance (p > 0.05).
      Almost 75% lesions were supratentorial, 25% infratentorial (p < 0.05). Focal
      neurological deficite (FND) was dominant clinical presentation in 52.8%. FND was
      dominant in 52.6% female, but without statistical singnificans (p > 0.05).
      Clinical presentation according the age was not statisticaly significant (p >
      0.05). Clinical presentation was very diferent according the size of lesion (p <
      0.001). FND as a sign of bleeding was in 57.9% supratentorial cavernomas and in
      42.1% infratentorial (p < 0.005). More than 1/3 patients have recurent bleeding
      with 21 atack of haemorrhage or almost 2 atack per patient. We find that dominant
      predictive factors for recurent haemorrhages are localisation and size of lesion.

PMID- 16813001
TI  - [Mathematical modeling in preooperative planning for reconstructive and plastic
      surgery].
AB  - Social importance of skin emphasizes an importance of quality of methods of
      planning for reconstructive and plastic surgery. With modern technical
      improvement the usage of complex mathematical model based on biomechanical
      characteristics of tissue is possible. Two- and three-dimensional model, expert
      systems and mechanical analysis are used. In this work we tested the system for
      mechanical analysis in preoperative planning of a simple procedure of the Z
      plastic, named the finite-element method. Computer model simulates tissue
      coverages. With geometrical data some physical characteristics are added. Complex
      surface of skin is marked by the grid divided in quadrangular elements.
      Mechanical consequences and definitive results of surgical procedure are analysed
      during the computer simulation of the action of tension of skin and suture
      material. In our analysis we found the finite-element method of great usefulness
      and noticed that "surgery simulators" might be an efficient way to speed-up
      learning curve in reconstructive surgery.

PMID- 16813003
TI  - Takayasu's aortoarteritis.
AB  - Surgical treatment of two female patients aged 32 and 41 years, with neurological
      problems causes by type I Takayasu's aortoarteritis, are presented here. Both of
      them were treated with by pass from ascending aorta to left common carotid and
      left subclavian arteries, using transsternal approach. During the follow up
      period (3.5 years for the first, and 2 years for the second patient) both
      patients were free of neurologic symptoms. Corticosteroid therapy was given to
      the first patient for controlling of active diseases, immediatelly after the
      operation and during the first three postoperative months. By this reason an
      infection af the proximal part of sternal wound was developed. MRI showed
      involvement of the vascular graft. Due to high risk of reoperation, medical
      treatment was performed. Takayasu's aortoarteritis is very unsommon in our
      country, as well as in other countries which don't belong to Far East. In cases
      with hemodinamic important arterial lesions produced disabling symptoms, a
      standard PTA and reconstructive vascular procedures are indicated. Takayasu's
      aortoarteritis is a complex disease. It requires combined dignostic and
      therapeutic approaches which produce satisffied long-term results.

PMID- 16813002
TI  - Patient with double cancer--successfully treated.
AB  - INTRODUCTION: Etiology of thrombosis in malignant diseases is multifactorial, and
      mechanisms that lead to thrombosis include release of the procoagulants from
      tumor cells (PC), factor related to bed rest, infections, as well as oncological
      therapy --chemotherapy, hormones, radiotherapy and surgical treatment.
      Thrombocytosis has frequently been found to be associated with various
      malignancies. CASE REPORT: 53 years old female patient hospitalised because of
      hypopharingeal cancer with metastasis in the left neck. Her state was complicated
      with deep leg vein trombosis and pseudomonas infection. Persistent thrombocitosis
      in laboratory monitoring indicated more adequate diagnostic procedures, which led
      to discovering of Chorioidal Malignant Mellanoma as a second cancer. She was
      treated: surgically, with antibiotics, with anticoagulants and radiotherapy.
      Patient was discharged from the hospital in good health condition, free of any
      other symptom of the malignant disease. CONCLUSION: Presense of thrombocytosis
      and idiopatic thrombosis can suggest occult malignancy. It would be prudent to
      further evaluate the relationship of trombotic events, trombocitosis and head and
      neck tumors. We suggest anticoagulants to prevent thromboembolic complications,
      affect the angiogenesis and prevent development of metastatic disease. It may
      lead to lower mortality rate.

PMID- 16813004
TI  - [Peritoneal hepatobiliary cystadenoma--case report].
AB  - Hepatobiliary cystadenoma with mesenchymal stroma are infrequent form of cystic
      neoplasm that may be found in females only. It is difficult to reach correct
      diagnosis prior to surgery. We are presenting a case of 32 years-old female
      referred to our institution for revealing a cause of discomfort and pain in right
      subcostal region whereas peritoneal hepatobiliary cystadenoma has been
      determined. Abdominal ultrasonography and computerized tomography revealed cystic
      lesion adjacent to gall bladder, which was initially thought to be of
      echynococcal origin. At surgery, a mesenterial cystic neoplasm has been revealed,
      having a close contact with gall bladder, without signs of its infiltration.
      Pathophysiology discovered hepatobiliary cystadenoma with mesenchymal stroma. Pre
      surgical differential diagnosis in hepatobiliary cystadenoma may be very
      difficult, especially if, like in the presented case, neoplasm has extra hepatic
      localization. Radical surgical excision is treatment of choice, concerning
      malignant potential of these neoplasms.

PMID- 16813005
TI  - Transmandibular approach to polycentric recurrent pleomorphic adenoma of the
      parapharyngeal space.
AB  - Surgery for tumors of the parapharyngeal space PPS) requires adequate exposure to
      identify and protect vital structures. Thus transcervical and transcervical
      transparotid approaches to the PPS may be enhanced by mandibulotomy for better
      visualisation. We have chosen this approach with single mandibulotomy just in
      front of foramen mentale and without lip incision. We present a 39 years old male
      who was undergone surgery for policentric recurrency of a pleomorphic adenoma of
      the parapharyngeal space.

PMID- 16813006
TI  - [Combined spinal-epidural anaesthesia for urgent Hartmann's procedure].
AB  - A 46- year old patient without previous history of general anaesthesia was
      admitted for urgent Hartman's procedure. The suspected tumor of sigmoid colon
      caused the obstructive ileus with extreme abdominal distension and threatened
      colon perforation. After induction of anaesthesia and adequate muscle relaxation
      it appeared that endotrh ileus because of possible regurgitation and aspiration.

PMID- 16813007
TI  - Delayed hemolytic transfusion reaction due to anti-Jk(a).
AB  - BACKGROUND: Kidd antibodies are very heterogeneous and difficult to detect. They
      have been frequently implicated in delayed hemolytic transfusion reactions
      (DHTRs). CASE REPORT: A 64 year old female (6 pregnancies, 2 deliveries, 4
      abortions) with none red cell (RBC) transfusions in the history was admitted to
      hospital due to pneumonia and severe anemia. On admittance hemoglobin (Hb) level
      was 63g/L and hematocrit (Ht) 0.21 L/L. The blood sample of the patient was sent
      to laboratory for serologic testing since RBC transfusions were required. Patient
      appeared to beO Rh(D)+ with negative both direct antiglobulin (DAT) and routine
      antibody screen (ID-DiaCell I+II+III-P). Three units of packed RBCs with negative
      crossmatch (tube method) were prepared. Patient received two units on Day 2 and
      one more on Day 3 without any discomfort. Hematological values after the third
      unit were: Hb 116g/L and Ht 0.37 L/L. On Day 6 she started to feel week, tired,
      with nausea and mild jaundice. Her Hb and Ht had dropped to 99 g/L and 0.33 L/L
      respectively, with tendency of dropping further (Day 7: Hb 83 g/L, Ht 0.26 L/L).
      Total serum bilirubin was 58.9 umol/L (normal range 20.5 umol/L) and direct
      fraction was 14.9 umol/L (normal range 7 umol/L). DTHR was suspected. Antibody
      identification performed by ID-DiaMed Gel Techique (GT) showed the presence of
      anti-Jk(a) with dosage phenomenon. All three previously transfused units were
      typed Jk(a) and the patient s RBCs were Jk(a-b+). She received two units of Jk(a)
      negative packed RBCs and was well enough to be discharged on Day 14. CONCLUSION:
      It is important to monitor clinical effect of transfusion regularly and to
      provide good team work between specialists of transfusion medicine and related
      medical staff. The policy of transfusion practice is to keep pretransfusion
      sample for three weeks and to perform cross-match tests on the samples no older
      then 24h and 48h respectively.

PMID- 16813008
TI  - Efficacy of oligodynamic metals in the control of bacteria growth in humidifier
      water tanks and mist droplets.
AB  - Antimicrobial capsules were evaluated for their effectiveness to control
      bacterial contamination of cool mist humidifiers. These capsules contain a
      mixture of silver and copper promoted alumina beads designed to release low
      concentrations of these oligodynamic metals into the reservoir water for bacteria
      control. The reservoir water and mist droplets from the humidifier units were
      tested for the presence of bacteria over a three-week period. A control unit
      (without capsule) showed significant bacterial contamination by day three, which
      increased throughout the three-week test period, in both the reservoir and mist
      droplets, whereas the antimicrobial capsules reduced contamination during the
      first week, and minimized the presence of bacteria, in both the reservoir water
      and mist droplets, to less than 2% of the control unit throughout the three-week
      test period. It was also observed that, after each inactive weekend, the initial
      discharge of bacteria via the mist droplets in the control unit was significantly
      higher than during daily use. However, initial bacterial discharge from the test
      unit following weekend inactivity never exceeded 0.5% of the control unit. In
      conclusion, these capsules containing oligodynamic metals are effective in
      controlling bacteria growth in humidifier water tanks and mist droplets.

PMID- 16813009
TI  - Evaluating Cryptosporidium and Giardia concentrations in combined sewer overflow.
AB  - Since the first identified Cryptosporidium outbreaks occurred in the 1980s and
      the massive 1993 Milwaukee, WI outbreak affected more than 400,000 people, the
      concern over the public health risks linked to protozoan pathogens
      Cryptosporidium and Giardia has grown. Cryptosporidium and Giardia, found in
      streams, rivers, groundwater, and soil, form hardy, disinfection-resistant
      oocysts and cysts. Both organisms are recognized causative agents of
      gastrointestinal illnesses linked to the consumption of contaminated surface or
      groundwater. This study, the first in a planned series to estimate the urban
      contribution to the total Cryptosporidium and Giardia receiving-water loads,
      focused on combined sewer overflow (CSO). CSOs are discharges of mixed untreated
      sewage and stormwater released directly into receiving waters during rainfall.
      This engineered relief is necessary to accommodate hydraulic strain when the
      combined rain and sanitary flows exceed the system capacity. Limited
      comprehensive data are available assessing the CSO discharge contribution as a
      source of these two pathogens. Works by States et al. and Gibson et al. each
      found Cryptosporidium and much greater Giardia concentrations in CSOs draining
      parts of Pittsburgh, PA. This project estimated the relative detection frequency
      and concentration of Cryptosporidium and Giardia in CSO. Analytical results were
      obtained using a modification of Method 1623, originally developed for much
      cleaner environmental samples. These data are useful for drinking water treatment
      plants located downstream of CSOs. It is also significant in determining the
      potential concentrations of parasites at treatment plant intakes and for
      assessing health risks for water contact and fishing activities. Commonly
      monitored indicator organisms (total coliform, fecal coliform, E. coli,
      Enterococcus, and fecal streptococcus), endospores, and selected physical and
      chemical parameters were analyzed to further describe the samples. CSO from urban
      areas was not found to be a significant contributor of Cryptosporidium, however,
      it was found to be a Giardia source.

PMID- 16813010
TI  - Identification of human fecal pollution sources in a coastal area: a case study
      at Oostende (Belgium).
AB  - From April to June 2001, a monitoring study at Oostende (Belgium) was conducted
      to obtain an insight into fecal pollution impairing water quality at this coastal
      area. Eight sampling sites were selected based on the historically low water
      quality at these sites compared to the remainder of the area. Indicator organisms
      such as fecal coliforms, Escherichia coli and fecal streptococci were monitored
      by plating. A real-time PCR assay for quantification of the human-specific HF183
      Bacteroides 16S rRNA genetic marker was used to detect human fecal pollution at
      the sampling sites. Human fecal pollution was detected at all sampling sites.
      However, the frequency of detection ranged from 30-100% and the amount of human
      specific Bacteroides markers recorded varied between the sampling sites.
      Concentrations of 10(7) human-specific Bacteroides markers per 1 to levels below
      the detection limit of the real-time PCR assay were recorded. Our results
      indicate that human fecal pollution is a re-occurring problem in certain areas.
      Of all the environmental parameters monitored during the study, only rainfall was
      strongly related to the detection of the indicator organisms and the human
      specific Bacteroides marker.

PMID- 16813011
TI  - Nutrient removal from septic effluents as affected by soil thickness and texture.
AB  - This study evaluated the effectiveness of soils with different textures and
      thickness to treat BOD, N and P eluted from household septic effluent. The
      assessments were accomplished by leaching undisturbed soil monoliths of 30, 45
      and 60 cm thickness and 25 cm in diameter, representing the four different
      textural groups and hydraulic loadings recommended by the Kentucky Health
      Department, with domestic wastewater effluent collected regularly from a
      household septic system. Effluent concentrations were monitored daily over a 15d
      period for biochemical oxygen demand (BOD), total-N, NH4-N, NO3-N and total-P
      concentrations. The results of the study indicate an alarming frequency of
      failure to comply with EPA criteria for BOD, total-N and NH4-N concentrations
      when using a 30 cm vertical separation distance between the bottom of the drain
      field and a limiting soil interface. The treatment performance was particularly
      poor in coarse-textured soils, apparently due to insufficient reactive surface
      area. Although biomat development over time is expected to improve the treatment
      for some of these parameters, the high influent levels of BOD pose great concerns
      for surface and groundwater contamination during the early stages of operation.
      Fine-textured soils generally provided better treatment efficiency and more
      consistent compliance with EPA standards for BOD, total-N, NH4-N and total-P, as
      well as greater nitrification/denitrification potential. Treatment efficiency and
      compliance usually improved with increasing soil depth, with the 60 cm thickness
      providing the most consistent performance and compliance with MDL requirements.
      Considering that increasing soil thickness requirements may be impractical in
      many marginal soils, complementary or alternative treatment technologies should
      be adopted to improve treatment efficiency and prevent further deterioration of
      the quality of water resources.

PMID- 16813012
TI  - Enteric viruses in inlet and outlet samples from sewage treatment plants.
AB  - Samples collected every two weeks from the inlet and outlet of three sewage
      treatment plants were screened for the presence of noro-, rota-, astro-, adeno-,
      hepatitis A- and circoviruses by (RT)-nested PCR, and for F-specific
      bacteriophages by isolation in Escherichia coli Famp. Plants A and B were
      secondary treatment plants and plant C used primary treatment. Noroviruses were
      detected in 43%, 53% and 24% of the inlet samples and 26%, 40% and 21% of the
      outlet samples from plants A, B and C, respectively. Astroviruses, rotaviruses
      and adenoviruses were more prevalent. Adenoviruses were detected in 96% of inlet
      and 94% of outlet samples, supporting the potential of these viruses as
      indicators of viral contamination from sewage. Hepatitis A virus and circoviruses
      were found only rarely. Reduction of infective viral particles during sewage
      treatment was evaluated using F-specific bacteriophages. The phages were reduced
      by, respectively, 99%, 87% and 0% in plants A, B and C, which corresponded to the
      observed differences in reduction of norovirus positive samples between the same
      plants. The study shows that the high viral load in sewage results in a discharge
      to the environment of a large amount of virus despite sewage treatment. On the
      other hand, the advantage of a more advanced treatment is demonstrated.

PMID- 16813013
TI  - Escherichia coli control in a surface flow treatment wetland.
AB  - A field experiment showed that numbers of Escherichia coli declined significantly
      when floating Lemna spp. plants were removed to create open water areas in a
      typical newly constructed surface flow treatment wetland in southern Ontario. It
      is suggested that E. coli declined immediately after Lemna removal because the
      Lemna was shading the water column from penetration by natural UV radiation, it
      was providing favourable attachment sites for the E. coli, and it was not
      allowing effective free exchange of oxygen from surface winds to the water column
      to maintain high enough dissolved oxygen supplies for predator zooplankton
      populations. Operators of wetland systems must have the specialized skills
      required to recognize the cause and the appropriate maintenance requirements to
      maintain efficient operation of such unconventional systems should E. coli
      numbers increase during the course of operation.

PMID- 16813014
TI  - Removal and transport mechanisms of arsenics in UF and NF membrane processes.
AB  - In this study, the removal and transport mechanisms of ionized and non-ionized
      arsenics through NF and UF membranes were systemically investigated. The charge
      repulsion between the membrane surface and arsenic ions was an important
      mechanism for the rejection of ions by a charged membrane. In addition, the
      effect of J0/k ratio was dependent on the membrane and ion charge, but the cross
      flow velocity was not significantly affected. Both diffusion and convection are
      proved to affect the transport of arsenic ions. The reflection coefficients
      (sigma) of both UF and NF membranes increased with increasing pH; the reflection
      coefficients of arsenate were higher than those of arsenite under the same
      operating conditions. The spiral-wound module exhibited slightly higher arsenate
      removal than the flat-sheet module under the same operating conditions.

PMID- 16813015
TI  - Use of a health information telephone line, Info-sante CLSC, for the surveillance
      of waterborne gastroenteritis.
AB  - The increasing frequency of waterborne outbreaks demonstrates that classic
      indicators used for the surveillance of the microbiological quality of drinking
      water have several gaps and that routine public health surveillance seems
      insufficient to allow for the rapid detection of these outbreaks. The main
      objective of this study was to evaluate the possibility of using a regional
      health information telephone line, 'Info-Sante CLSC' (Info-Health Local Community
      Health Centre), for the surveillance of waterborne gastroenteritis. This study
      measured the incidence rate of calls for acute gastrointestinal illness (AGI)
      placed to the Info-Sante CLSC line, investigated the relationship between the
      frequency of calls for AGI placed to the Info-Sante CLSC line and the turbidity
      of the treated water in the Quebec City drinking water plant and evaluated the
      relevance and the conditions of use of the Info-Sante CLSC system for the
      surveillance of waterborne enteric illness. A relationship between the turbidity
      and the calls for AGI placed to Info-Sante CLSC line was observed. Significant
      time lags (11, 15 and 17 days prior to the outcome) were identified in the final
      model derived from a Poisson model using generalized additive models (GAM) as a
      time series analysis. Some recommendations to improve the system were formulated
      even though the system already seems to be useful for the surveillance of
      waterborne enteric diseases.

PMID- 16813016
TI  - Toxic cyanobacteria and their toxins in standing waters of Kenya: implications
      for water resource use.
AB  - Phytoplankton biodiversity studies in Kenya's standing waters were carried out
      between 2001 and 2003. Toxin producing cyanobacteria were recorded in twelve
      water bodies. Microcystis and Anabaena were the most common species in
      freshwaters while Anabaena and Anabaenopsis were common in alkaline saline lakes.
      Seven lakes with cyanobacteria blooms and a hot spring had detectable levels of
      microcystins and anatoxin-a. Cell bound microcystins (LR equivalents)
      concentration ranged from 1.6-19800 microgg(-1) Dry Weight (DW) while anatoxin-a
      varied from below the limit of detection to 1260 microgg(-1) DW. In alkaline
      saline lakes, microcystins and anatoxin-a were also present in stomach contents
      and liver samples of dead flamingos. Monoculture strains of A. fusiformis from
      Lakes Sonachi and Bogoria had detectable levels of microcystins while anatoxin-a
      was present in strains isolated from Lakes Sonachi, Bogoria and Nakuru. Two
      freshwater sites, Nyanza Gulf (L. Victoria) and Lake Baringo recorded cyanotoxin
      concentration exceeding WHO'S upper limit of 1.0 microgl(-1) for drinking water.
      The results confirm that cyanotoxins could have played a role in the mortality of
      flamingos in Lakes Bogoria and Nakuru. The implications of these findings on
      water resource use, measures to be taken to reduce the risk of exposure and
      eutrophication control steps to reduce cyanobacteria bloom formation are
      considered in this paper.

PMID- 16813017
TI  - Delineation of a chemical and biological signature for stormwater pollution in an
      urban river.
AB  - Stormwater is a major source of Escherichia coli in urban waterways. This study
      assessed the chemical and bacterial contaminant load in stormwater entering an
      urban river using chemical analyses, E. coli enumeration and antibiotic
      resistance testing. Inline monitoring of five major stormwater outfalls revealed
      that E. coli concentrations can range from 100 to >240,000 CFU 100ml(-1) in
      stormwater; 15% of the samples contained >240,000 CFU 100 ml(-1). E. coli levels
      increased from <200 CFU 100ml(-1) to between 1,500 and >20,000 CFU 100ml(-1) in
      the receiving waters following storm events. Metals and nutrients were
      significantly elevated (p < 0.05) in inline stormwater samples compared with
      baseflow river water. Chromium, zinc, lead and total phosphorus were co
      ordinately elevated in stormwater, but E. coli levels did not correlate to this
      chemical signature. E. coli isolates from stormwater and river water samples (n =
      2,478) were tested for resistance to 10 antibiotics and compared with over 1,800
      isolates from human and non-human sources. The antibiotic resistance frequencies
      of isolates from human sources were considerably higher than those found in non
      human sources. Isolates from human sources were resistant to multiple
      antibiotics; however, no specific multiple resistance pattern was found. One of
      five stormwater outfalls tested contained E. coli resistant to antibiotics at
      frequencies that were not significantly different from those of E. coli isolates
      from wastewater treatment plant influent (p < 0.05). The results from antibiotic
      resistance testing suggested that the elevated E. coli levels observed after
      storm events are a mixture of human and non-human sources. The results of this
      study demonstrate that there is a considerable E. coli load to receiving waters
      from stormwater and that sanitary sewage inputs may not be limited to recognized
      sewer overflows.

PMID- 16813018
TI  - PFGE analysis of enterococci isolates from recreational and drinking water in
      Greece.
AB  - Biotyping and DNA fingerprinting by pulsed-field gel electrophoresis were applied
      to a collection of enterococci recovered from recreational and drinking water, in
      order to identify possible genetic relationships. Clinical strains of hospital
      origin were compared to the environmental isolates. A total of 104 enterococci
      were isolated from 128 recreational water (94 marine and 34 river water) and 470
      drinking water supplies (440 municipal and 30 natural spring water samples).
      Sixty-two isolates were characterised as Enterococcus faecium recovered from all
      sources, 32 E. faecalis (from all sources), 4 E. durans (from marine, river and
      municipal water), 4 E. gallinarum (from marine water) and 2 E. avium (from marine
      and municipal water). Biotypes, determined with API20Strep, among E. faecium were
      correlated with certain environmental sources, while antibiotypes, determined
      with Etest, did not reveal any relationship to the sample origin. Even though
      genetic diversity was observed among the studied strains, common clonal types
      were also identified in different sources, suggesting a possible common origin of
      the enterococci. Cluster analysis revealed a genetic relationship between certain
      environmental E. faecium and clinical strains.

PMID- 16813019
TI  - Bottled water versus tap water: understanding consumers' preferences.
AB  - The consumption of bottled water has been increasing consistently over the last
      decade, even in countries where tap water quality is considered excellent. This
      paper discusses some of the reasons why people decide for an option that is often
      more expensive and less comfortable than tap water. Consumer surveys usually
      stress two main factors: dissatisfaction with tap water organoleptics (especially
      taste) and health/risk concerns. However, many other factors are involved,
      including demographic variables and the perceived quality of the water source.
      Trust in tap water companies also seems to influence public behaviour. A clearer
      picture of bottled water consumption can be achieved when different aspects are
      considered.

PMID- 16813020
TI  - The future of stapes surgery.

PMID- 16813021
TI  - Traumatic posterior tympanic membrane perforation.

PMID- 16813022
TI  - The vomeronasal (Jacobson's) organ.

PMID- 16813023
TI  - Reinnervation of the paralyzed vocal fold.

PMID- 16813024
TI  - Laryngeal chondrosarcoma.

PMID- 16813025
TI  - Nasopharyngeal carcinoma.

PMID- 16813026
TI  - Chondrodermatitis nodularis chronica helicis.

PMID- 16813027
TI  - Combining multiple surgical techniques for maximum scar camouflage.

PMID- 16813028
TI  - Monitor changes in patients' insurance.

PMID- 16813029
TI  - The effect of stapedotomy on tinnitus in patients with otospongiosis.
AB  - Stapedotomy is primarily performed to treat hearing loss secondary to
      otospongiosis, although some patients find that the accompanying tinnitus is more
      bothersome than the hearing loss. We prospectively studied 23 consecutive
      patients with tinnitus secondary to otospongiosis who had undergone stapedotomy,
      and we compared their pre- and postoperative medical and audiologic findings.
      Patients' annoyance with their tinnitus was quantified by means of a visual
      analog scale, and their air-conduction thresholds were determined by measurements
      of a 4-frequency pure-tone average (0.5, 1, 2, and 4 kHz). Statistical analysis
      was performed using the paired Student's t test and Fisher's exact test. In the
      group as a whole, the mean tinnitus annoyance visual analog scores were 8.34
      preoperatively and 1.56 postoperatively, a highly significant difference.
      Clinically, 22 of the 23 patients (95.7%) achieved satisfactory control of their
      tinnitus (improvement or complete resolution) following stapedotomy. With respect
      to hearing loss, all patients clinically improved postoperatively, and audiometry
      confirmed improvement at all 4 frequencies between 0.5 and 4 kHz. An air-bone gap
      of less than 10 dB was noted in 17 patients (73.9%). We conclude that in addition
      to improving hearing, stapedotomy also provides good control of tinnitus.

PMID- 16813030
TI  - Tympanostomy tube obstruction related to ototopical drug therapy.
AB  - Obstruction of tympanostomy tubes is a potentially significant complication,
      sometimes requiring replacement of the nonfunctioning tube. Early blockage can
      occur secondary to bleeding during the tube placement procedure. Delayed
      obstruction is usually caused by inspissated secretions or epithelial casts. We
      briefly report our treatment of 9 cases of delayed ventilation tube obstruction
      that were associated with the use of an ototopical antibiotic/steroid suspension.

PMID- 16813031
TI  - Tympanostomy tubes for otitis media: quality-of-life improvement for children and
      parents.
AB  - We measured quality of life issues for both children and their parents on the
      premise that parental quality of life should be an aspect of cost-effectiveness
      in otitis media treatment. The patients were less than 18 years of age and had
      had myringotomy with tube insertion at the head and neck surgery department of a
      large health maintenance organization. Quality of life for patients, parents, and
      caregivers was evaluated by telephone survey of parents or caregivers and by
      retrospective chart review of the number of pre- and postoperative healthcare
      visits and antibiotic usage. Chart review showed a significant postoperative
      reduction in the number of clinic visits and in use of antibiotic drugs after
      insertion of tympanostomy tubes. Improved postoperative hearing was noted, and
      tympanostomy tube insertion was shown to be safe. The chart-review cost analysis
      showed that tympanostomy tube insertion is a cost-effective treatment for otitis
      media in children, and the telephone survey results showed that it improves
      quality of life for children and their parents or other caregivers.

PMID- 16813032
TI  - Comparison of intranasal hypertonic dead sea saline spray and intranasal aqueous
      triamcinolone spray in seasonal allergic rhinitis.
AB  - Intranasal corticosteroids are well known to be efficacious in the treatment of
      allergic rhinitis. Nasal irrigation with saline, including hypertonic saline, has
      long been recommended for the treatment of sinonasal disease, and it has been
      shown to have a positive effect on the physiology of the nasal mucosa. Until now,
      no study of the clinical efficacy of intranasal hypertonic Dead Sea saline as a
      monotherapy for seasonal allergic rhinitis has been reported. We conducted a
      prospective, randomized, single-blind, placebo-controlled comparison of
      intranasal hypertonic Dead Sea saline spray and intranasal aqueous triamcinolone
      spray in 15 patients with seasonal allergic rhinitis. Results were based on a 7
      day regimen. Based on Rhinoconjunctivitis Quality of Life Questionnaire scores,
      clinically and statistically significant (p < 0.0001) improvements were seen in
      both active-treatment groups; as expected, the corticosteroid spray was the more
      effective of the two treatments. No significant improvement occurred in the
      control group. Our preliminary results not only confirm the efficacy of
      intranasal corticosteroid therapy in moderate-to-severe allergic rhinitis, they
      also suggest that the Dead Sea saline solution can be an effective alternative in
      mild-to-moderate allergic rhinitis, particularly with respect to nasal and eye
      symptoms. The hypertonicity of the Dead Sea solution may have a positive effect
      on the physiology of the nasal mucosa by improving mucociliary clearance. In
      addition, the dominant cation in the Dead Sea solution--magnesium--probably
      exerts anti-inflammatory effects on the nasal mucosa and on the systemic immune
      response.

PMID- 16813033
TI  - Brown tumor of the facial bones: case report and literature review.
AB  - Brown tumor, an uncommon focal giant-cell lesion, arises as a direct result of
      the effect of parathyroid hormone on bone tissue inpatients with
      hyperparathyroidism. The initial treatment involves the correction of
      hyperparathyroidism, which usually leads to tumor regression. We report a case of
      brown tumor of the right nasal fossa in a 71-year-old woman. The tumor had caused
      nasal obstruction and epistaxis. Laboratory evaluation revealed that the patient
      had primary hyperparathyroidism. Anatomicopathologic investigation revealed the
      presence of a giant-cell tumor We performed a partial parathyroidectomy, but the
      tumor in the right nasal fossa failed to regress. One year later we performed
      surgical resection of the lesion. The patient recovered uneventfully, and she
      remained asymptomatic and recurrence-free at the 1-year follow-up. Facial lesions
      with histologic features of a giant-cell tumor should be evaluated from a
      systemic standpoint. Hyperparathyroidism should always be investigated by
      laboratory tests because most affected patients are asymptomatic. Surgical
      resection of a brown tumor should be considered if the mass does not regress
      after correction of the inciting hyperparathyroidism or if the patient is highly
      symptomatic.

PMID- 16813034
TI  - Leiomyosarcoma of the larynx: A case report.
AB  - Leiomyosarcoma of the larynx is an extremely rare neoplasm; only about 50 cases
      have been reported in the English-language literature. We report a new case of
      laryngeal leiomyosarcoma in a 65-year-old man. The metastatic work-up was
      negative, and the patient underwent total laryngectomy. He remained disease-free
      12 months postoperatively.

PMID- 16813035
TI  - Rhabdomyoma of the larynx: case report and clinical and pathologic review.
AB  - We describe a case involving a 79-year-old man with symptoms of slowly
      progressive hoarseness resulting from a rhabdomyoma originating deep to the right
      true and false vocal folds. We also review the pathology and radiologic findings
      of rhabdomyoma.

PMID- 16813036
TI  - Advantages of perforator flaps in reconstruction of complex defects of the head
      and neck.
AB  - Microsurgical transfer of vascularized tissue during the past three decades has
      allowed highly complicated postoncologic defects in the head and neck region to
      be reconstructed. Recently, perforator flaps have been used to reduce
      postoperative pain, shorten hospital stay, and lessen donor-site complications.
      These flaps are offsprings of previously known musculocutaneous and
      fasciocutaneous flaps and are harvested with preservation of the underlying
      muscular and fascial structures. The vascularized skin and soft-tissue envelope
      is supplied by perforating branches from the parent vessel. Less is known about
      the performance of these flaps in the head and neck region. During a 4-year
      period, 22 patients at our institution underwent reconstruction of the head and
      neck region with deep inferior epigastric perforator (DIEP) or thoracodorsal
      artery perforator (TDAP) flaps. All but one of the flaps survived. Advantages
      noted include: (1) longer vascular pedicles, (2) less postoperative pain, (3)
      less donor-site deformity, (4) improved aesthetic outcome, (5)potential for a
      neurosensory flap, (6) potential for an osteocutaneous flap, and (7) ease of
      postoperative radiologic follow-up. The DIEP flap can be harvested concurrent
      with oncologic resection, with the patient in the supine position. The TDAP flap
      is dissected with the patient in the decubitus position, creating an additional
      step to change operative position, and separates extirpative and reconstructive
      stages.

PMID- 16813037
TI  - A computerized test of self-control predicts classroom behavior.
AB  - We assessed choices on a computerized test of self-control (CTSC) for a group of
      children with features of attention deficit hyperactivity disorder (ADHD) and a
      group of controls. Thirty boys participated in the study. Fifteen of the children
      had been rated by their parents as hyperactive and inattentive, and 15 were age-
      and gender-matched controls in the same classroom. The children were observed in
      the classroom for three consecutive mornings, and data were collected on their
      activity levels and attention. The CTSC consisted of two tasks. In the delay
      condition, children chose to receive three rewards after a delay of 60 s or one
      reward immediately. In the task-difficulty condition, the children chose to
      complete a difficult math problem and receive three rewards or complete an easier
      problem for one reward. The children with ADHD features made more impulsive
      choices than their peers during both conditions, and these choices correlated
      with measures of their activity and attention in the classroom.

PMID- 16813038
TI  - The efficacy of noncontingent escape for decreasing children's disruptive
      behavior during restorative dental treatment.
AB  - We evaluated the effectiveness of a dentist-implemented behavioral intervention
      in which brief escape from dental treatment was provided on a regular basis,
      independent of the child's behavior. Within a multiple baseline design across
      subjects, 5 children, ages 4 to 7 years, were provided with temporary escape from
      dental treatment on a fixed-time schedule. The intervals were signaled by an
      electronic timer worn by the dentist. Clinically significant reductions were
      observed in physically disruptive behavior across all 5 children with the
      introduction of noncontingent escape, and verbally disruptive behavior was
      markedly reduced in 4 of the 5 children. In addition, the dental staff s use of
      physical restraint was reduced to near zero across all 5 children. The research
      extends the literature in both clinical dentistry and in applied behavior
      analysis by demonstrating that a dentist can easily and effectively implement
      noncontingent reinforcement to produce clinically significant and socially
      important changes in children's health behavior.

PMID- 16813039
TI  - Assessment of deviant arousal in adult male sex offenders with developmental
      disabilities.
AB  - Ten individuals, residing in a treatment facility specializing in the
      rehabilitation of sex offenders with developmental disabilities, participated in
      an arousal assessment involving the use of the penile plethysmograph. The arousal
      assessments involved measuring change in penile circumference to various
      categories of stimuli both appropriate (adult men and women) and inappropriate
      (e.g., 8- to 9-year-old boys and girls). This approach extends the existing
      assessment literature by the use of repeated measurement and single-subject
      experimental design. Data from these assessments were analyzed to determine if
      clear and informative outcomes were obtained. Overall, three general patterns of
      results emerged. Some participants showed differentiated deviant arousal or
      higher levels of arousal to specific inappropriate stimuli (deviant is a term
      used in the existing sex-offender literature to describe this type of arousal).
      Other participants showed undifferentiated deviant arousal, in which case they
      showed nonspecific arousal to inappropriate stimuli. The remaining participants
      showed no arousal to inappropriate stimuli but did show arousal to appropriate
      stimuli. Implications for assessment, treatment, and future directions are
      discussed.

PMID- 16813040
TI  - Some determinants of changes in preference over time.
AB  - Results of longitudinal studies suggest that the stability of preferences varies
      across individuals, although it is unclear what variables account for these
      differences. We extended this work by conducting periodic assessments of
      preference for leisure activities over 3 to 6 months with 10 adults with
      developmental disabilities. Although previous research has collectively shown
      that preferences identified via repeated assessment are highly variable, our
      results showed that preferences were relatively stable for the majority (80%) of
      participants. In an attempt to identify some environmental determinants of shifts
      in preference, we provided extended daily access to high-preference items
      (preference-weakening manipulation) and paired access to low-preference items
      with social and edible putative reinforcers during brief sessions (preference
      strengthening manipulation). Preference assessments continued over the course of
      these manipulations with 2 participants. Results showed that changes in
      preference across time could be produced systematically and suggest that
      naturally occurring changes in establishing operations or conditioning histories
      contribute to temporal shifts in preference. Implications for preference
      assessments, reinforcer usage, and planned attempts to change preferences are
      discussed.

PMID- 16813041
TI  - An evaluation of computer-based programmed instruction for promoting teachers'
      greetings of parents by name.
AB  - Although greeting parents by name facilitates subsequent parent-teacher
      communication, baseline measures revealed that 4 preschool teachers never or
      rarely greeted parents by name during morning check-in. To promote frequent and
      accurate use of parents' names by teachers, the effects of a fully automated
      computerized assessment and programmed instruction (CAPI) intervention were
      evaluated in a multiple baseline design. The CAPI intervention involved
      assessment and training of relations among parents' and children's pictures and
      names, and produced rapid learning of parent names. The CAPI intervention also
      resulted in substantial improvements in the classroom use of parents' names for 3
      of the 4 teachers; however, a supervisor-mediated feedback package (consisting of
      instructions, differential reinforcement, and error correction) was necessary to
      maintain name use for 2 of those teachers. The practical strengths and
      limitations of computer-based teacher training are discussed.

PMID- 16813042
TI  - Effects of training, prompting, and self-monitoring on staff behavior in a
      classroom for students with disabilities.
AB  - This study extended the limited research on the utility of tactile prompts and
      examined the effects of a treatment package on implementation of a token economy
      by instructional assistants in a classroom for students with disabilities. During
      baseline, we measured how accurately the assistants implemented a classroom token
      economy based on the routine training they had received through the school
      system. Baseline was followed by brief in-service training, which resulted in no
      improvement of token-economy implementation for recently hired instructional
      assistants. A treatment package of prompting and self-monitoring with accuracy
      feedback was then introduced as a multiple baseline design across behaviors. The
      treatment package was successfully faded to a more manageable self-monitoring
      intervention. Results showed visually significant improvements for all
      participants during observation sessions.

PMID- 16813043
TI  - A preliminary analysis of self-control with aversive events: the effects of task
      magnitude and delay on the choices of children with autism.
AB  - When faced with a choice between two aversive events, a person exhibits self
      control by choosing a smaller, more immediate aversive event over a larger,
      delayed aversive event. Task demands are often aversive to children with autism
      and other developmental disabilities. The purpose of this study was to evaluate
      behavioral sensitivity to differences in the amount and delay of tasks as part of
      a preliminary study on self-control. Participants were 2 children with autism who
      engaged in problem behavior maintained by escape. Results indicated a lack of
      self-control with respect to choosing between two aversive tasks and suggested
      potential strategies for increasing self-control (i.e., choosing a small
      immediate task over a large delayed task).

PMID- 16813044
TI  - Generalization of tacting actions in children with autism.
AB  - This intervention compared the effects of two procedures on the generalization of
      a tacting repertoire (labeling) in 6 children with autism spectrum disorder. In
      one procedure the verbal antecedent stimulus "What is she doing?" appeared
      together with a person performing an action; in the other procedure, the
      antecedent stimulus was just the presence of the action. In initial tests,
      children emitted tacts only when the action was presented with the verbal
      antecedent. Thereafter, they learned to tact an action without the verbal
      antecedent and received tests to evaluate generalization to another action.
      Results indicated that in order to obtain generalization of tacting actions, it
      was necessary to learn to tact other actions without the verbal antecedent as
      well as learning to tact the action with the verbal antecedent. These findings
      have relevance for generalization of tacting actions from control by verbal
      antecedents to natural conditions and the production of spontaneous language.

PMID- 16813045
TI  - A preliminary examination of the evocative effects of the establishing operation.
AB  - We attempted to isolate the evocative effects of the establishing operation for
      positively reinforced problem behavior with 2 participants. The study consisted
      of three phases. First, a functional analysis identified tangible items
      (Participant 1) and attention (Participant 2) as maintaining problem behavior.
      Second, access to tangible items and attention was systematically controlled
      (continuous access vs. no access) immediately prior to functional analysis
      sessions in which these consequences were delivered contingent on problem
      behavior. Results of this phase indicated that problem behavior occurred at
      higher levels when access to tangible items and attention was restricted. In the
      third phase, prior access was again controlled, but problem behavior produced no
      consequences. Results of this final phase indicated that problem behavior
      occurred at higher levels during extinction sessions when participants did not
      have prior access to the reinforcers.

PMID- 16813046
TI  - Some effects of stimulant medication on response allocation: a double-blind
      analysis.
AB  - Children who are diagnosed with attention deficit hyperactivity disorder (or who
      engage in behavior consistent with such a diagnosis) are often prescribed
      stimulant medications for hyperactive or inattentive behaviors. However, the
      mechanisms by which stimulant medications affect individuals' behavior are rarely
      evaluated. The purpose of the current study was to evaluate the effects of
      stimulant medication on response allocation when antecedents and consequences
      were held constant and equated. Results indicated that the presence of an
      amphetamine medication (Adderall) influenced response allocation across two
      concurrently available responses while all other stimulus conditions were held
      constant.

PMID- 16813047
TI  - Increasing donations to supermarket food-bank bins using proximal prompts.
AB  - There has been little research into interventions to increase participation in
      donating items to food-bank bins. In New Zealand, there has been an increased
      demand from food banks (Stewart, 2002). This study demonstrated that point-of
      sale prompts can be an effective method of increasing donations to a supermarket
      food-bank bin.

PMID- 16813048
TI  - Enhancing frequency recording by developmental disabilities treatment staff.
AB  - We evaluated a staff training and management package for increasing accuracy of
      recording frequency of problem behavior in a residential care facility. A
      multiple baseline design across the first and second work shifts showed that 2 of
      8 participants increased their accuracy following in-service training, and all 8
      improved during a condition with supervisor presence and feedback. Improvements
      were maintained when feedback was removed and generalized to activity periods
      when neither supervisor presence nor feedback was provided. Other staff behavior
      was not adversely affected by the intervention package.

PMID- 16813049
TI  - The effects of goal setting on rugby performance.
AB  - Goal-setting effects on selected performance behaviors of 5 collegiate rugby
      players were assessed over an entire competitive season using self-generated
      targets and goal-attainment scaling. Results suggest that goal setting was
      effective for enhancing task-specific on-field behavior in rugby union.

PMID- 16813050
TI  - [Resolution of the Scientific-and Practical Conference on Organization of
      Tuberculosis Hospital Work].

PMID- 16813051
TI  - [Sarcoidosis as a biological and medical problem].
AB  - The paper considers the basic biological, medical, and organizational problems
      that investigators and practitioners of different specialties come up against in
      recognizing sarcoidosis. Particular emphasis should be placed on the etiology and
      pathogenesis of sarcoidosis, the selection of management policy. Russia's
      currently established situation associated with the duration of a follow-up of
      patients with sarcoidosis is analyzed and the priorities of researches and
      organizational-and-practical work are proposed.

PMID- 16813052
TI  - [Cardiac lesion in sarcoidosis].

PMID- 16813053
TI  - [Diagnosis of sarcoidosis of the brain].
AB  - Based on 15 years' their own experience and clinical observations of 65 patients
      with sarcoidosis of the brain, the authors have formulated diagnostic algorithms
      and a battery of studies that can suspect this disease. Since the clinical
      manifestations of sarcoidosis of the brain are non-specific, particularly at the
      early stages of its development, the condition of its recognition is the
      application of all required high-informative diagnostic neuroimaging techniques
      that are available to a neurological clinic. Nevertheless, sarcoidosis cannot be
      timely and correctly recognized in all cases. Diagnostic errors in its
      recognition are caused by the fact that X-ray computed tomography and/or magnetic
      resonance imaging is untimely made, tomographic changes are erroneously
      interpreted, and the studies are conducted improperly.

PMID- 16813054
TI  - [Evaluation of the efficiency of various treatment regimens for patients with
      newly-detected sarcoidosis in the Republic of Tatarstan].
AB  - The natural history of sarcoidosis was analyzed in 279 patients with its history
      of as long as 2 years among the 832 with this disease registered in the Republic
      of Tatarstan in 1999 to 2002. The patients were divided into 3 groups: (1) 79
      (28.3%) receiving systemic glucocorticosteroids (SGS); (2) 146 (52.3%) patients
      having therapy without SGS; (3) 54 (19.3%) patients receiving no drug therapy,
      but they were followed up by a physician. There was no strong evidence for that
      it was expedient to use prednisolone in most of patients. Prednisolone exerted a
      significant effect on clinical manifestations, laboratory values, and radiation
      pattern in patients with sarcoidosis, but more commonly (28.9%) led to its
      relapses than alternative treatment and active follow-up. Patients treated with
      prednisolone and other drugs and those untreated showed no significant
      differences in the frequency of cases of a worse X-ray pattern during 28 years.
      It is advisable to follow an active observation policy in patients having a
      stable course of sarcoidosis, by restricting indications for the use of
      prednisolone in those who have apparently progressive or threatening
      extrapulmonary manifestations of the disease (heart, nervous system, eyes).

PMID- 16813055
TI  - [Long-term results of treatment and prediction in patients with sarcoidosis].
AB  - The long-term results of treatment in patients with different clinical forms of
      sarcoidosis were studied, by using both prednisolone and nonsteroidal anti
      inflammatory drugs (NSAIDs). No therapeutic measures were implemented in some
      patients. The total number of patients was 1587; the time of a follow-up was 2 to
      10 years after completion of treatment or, in the latter's absence, after
      detection of the disease. The frequency of spontaneous regression in patients
      with Stage I pulmonary sarcoidosis was 57%. That in patients with its Stage II
      and generalized sarcoidosis was relatively low. Evaluation of the efficiency of
      different prednisolone treatment regiments showed that there was the highest cure
      rate in Stage I pulmonary sarcoidosis when the initial dose of the agent was 0.75
      1 mg/kg every other day. This prednisolone treatment regimen did not exhibit any
      great advantages when applied to patients with Stage II pulmonary sarcoidosis and
      generalized sarcoidosis. Comparison of the use of prednisolone, 0.5 mg/kg, every
      day or every other day yielded about equal results during long-term follow-ups. A
      rather noticeable effect was achieved when NSAIDs were administered. However,
      these drugs were used in relatively minor pathological changes; and some such
      patients were observed to have signs of initial spontaneous regression just
      before the initiation of therapy.

PMID- 16813056
TI  - [Endobronchial biopsy in the diagnosis of pulmonary sarcoidosis].
AB  - Bronchofiberscopy (BFS) with endobronchial biopsy (EBB) was performed in 66
      patients with pulmonary sarcoidosis (PS). Transbronchial biopsy (TBB) was made in
      49 patients from this group to compare the diagnostic value of EBB and TBB. The
      normal endoscopic picture was observed in 19.6% of patients. Bronchial mucosal
      hypervascularization and thickening were found in 25.7% of cases; the signs of
      enlarged bronchopulmonary lymph nodes were detected in 13.6%; catarrhal
      endobronchitis in 10.6%, and tuberosity changes in 4.5%. Epithelioid granulomas
      in the bronchial mucosa were identified in 37.8% of cases (30.75 and 39.6% in the
      intact and abnormal mucosa, respectively). The diagnostic value of TBB was 65.3%.
      EBB could reveal epithelioid-cell granulomas in 4 of the 17 patients with
      negative TBB. The findings suggest that BFS with EBB should be included as a
      necessary diagnostic method for the examination of patients with PS.

PMID- 16813057
TI  - [Side effects of corticosteroidal therapy in patients with chronic forms of
      sarcoidosis].
AB  - The biological activity of glucocorticosteroids (GCS) is that there is always a
      risk of complications during repeated long courses of therapy in patients with
      recurrent sarcoidosis even if treatment is correctly organized. The clinical side
      effects of GCS were studied in 99 patients identified in 1995 to 2002, who had a
      chronic process and had been continuously treated with GCS for 2 years or more.
      The altered adrenal function by tile type of hypercorticism was observed in 73
      (73.7%) patients, subsequent hypocorticism developed in 60 (60.6%). Impairments
      in electrolyte balance and protein, carbohydrate, and fat metabolism were seen in
      74 (74.6%) patients; impaired functional disintegration of the hypothalamic
      pituitary system in 26 (26.2%), allergic reactions in 12 (12.1%), complications
      of mixed genesis (gastritis and erosions of the stomach and intestine) in 20
      (20.2%). A teratogenic effect was not observed. The most effective treatment of
      sarcoidosis--oral GCS--frequently leads to the occurrence of a great deal of side
      effects and drastically changes the quality and style of life in a patient with
      sarcoidosis. The correct and timely use of GCS in sarcoidosis requires a complete
      understanding of the pharmacological properties and features of their action,
      consideration of undesirable effects of treatment and the heath status of a
      patient with underlying diseases.

PMID- 16813058
TI  - [Sarcoidosis: markers of its poor course, extracorporeal immunomodulation].

PMID- 16813059
TI  - [Steroidal leukocytosis and immediate results of treatment in patients with
      sarcoidosis].
AB  - The occurrence of steroidal leukocytosis at early stages of an observation may,
      to a certain extent, serve an objective criterion for predicting the pronounced
      immediate results of treatment in first detected patients with sarcoidosis (that
      of intrathoracic lymph nodes and the lung in particular) and thus makes it
      possible to judge the adequacy of therapy in the inpatient setting. When
      steroidal leukocytosis is absent, it is necessary to differentiately decide
      whether it is expedient to correct a hormonal therapy regimen in order to achieve
      the optimal results of its efficiency.

PMID- 16813060
TI  - [Respiratory mechanics in patients with stage III pulmonary sarcoidosis and
      idiopathic fibrosing alveolitis: similarities and differences].
AB  - Impaired function of the lung was studied in 28 patients with Stage 111 pulmonary
      sarcoidosis and 17 patients with idiopathic fibrosing alveolitis (IFA). The study
      involved spirography, body plethysmography, and esophageal probing of respiratory
      mechanics. In patients with Stage III pulmonary sarcoidosis, the mechanics of
      respiration has the following similarities: restrictive ventilation disorder is
      revealed in IFA; the functional syndrome with a predominance of restriction is
      also detectable in some patients with Stage III sarcoidosis; significant
      differences are found in patients with IFA and Stage III pulmonary sarcoidosis:
      there is no marked impaired patency of peripheral bronchi in IFA; and all the
      functional changes found suggest that there is an increase in lung tissue
      rigidity and a decrease in the capacity of the lung to straighten; in Stage III
      sarcoidosis, of great importance is a marked impairment of patency of
      peripherally located bronchi, which is associated with the increase of this or
      that degree of lung compliance and in the retraction index.

PMID- 16813061
TI  - [Early diagnosis of pulmonary hemodynamic disorders in patients with pulmonary
      sarcoidosis].
AB  - A hundred and eleven patients with pulmonary sarcoidosis (PS) were examined to
      detect early impairments of pulmonary hemodynamics and myocardial function. A
      package of examinations included Doppler echocardiography at rest and with the
      Valsalva test, as well as electrocardiography and myocardial scintigraphy. In
      patients with early PS, right ventricular diastolic dysfunction is shown to be
      preceded by systolic dysfunction, as manifested itself in the altered ratio of
      different phases of right ventricular filling. As a method for early diagnosis of
      latent hypertension, the authors propose to use the Valsalva test to create a
      short-term volume overload of the right cardiac cavities. The study has indicated
      that left cardiac dilatation, decreased ejection fraction, left ventricular
      diastolic dysfunction, and the presence of large focal portions of fibrosis in
      the ventricular myocardium, interventricular septum, and papillary muscles can be
      considered to be early Doppler echocardiographic signs of sarcoidosis of the
      heart in patients with PS.

PMID- 16813062
TI  - [Immunophenotyping of epithelioid-cell granulomas in sarcoidosis].
AB  - The specimens of biopsy of the lung and lymph nodes from 24 patients with
      sarcoidosis were immunophenotyped. The monoclonal antibody panel for
      immunophenotyping the monocyte-macrophage cells included HLA-DR, CD64, CD163;
      CD7, CD3, CD4, CD8, HLA-DR, and CD20 were used to assess lymphocytic populations.
      In sarcoidosis, the majority of cell elements of a granuloma are in a state of
      activation, as evidenced by HLA-DR expression on the epithelioid, giant cells, T
      lymphocytes (which was observed in more than in 90% of cases), the extent of this
      expression decreasing as fibrosis develops. There is a statistically significant
      correlation between the presence of individual lymphocytic subpopulations and
      monocyte-macrophage cells in the granuloma. No clear relationship of the
      phenotype of a granuloma to the clinical form (stage) of sarcoidosis suggests
      that is based on the common self-sustaining process of formation, functioning,
      and involution of granulomas, which has no direct agreements in the X-ray and
      laboratory manifestations of the disease.

PMID- 16813063
TI  - [A system for selection of indices to characterize the tuberculosis
      epidemiological situation and the quality of tuberculosis-controlling work].
AB  - Effective management, including that in phthisiology is impossible without
      assessing the conditions and divisions of work. The accuracy and objectivity of
      estimates, integral ones in particular, depends on what specific parameters are
      used to evaluate objects. A scientifically grounded three-step system is proposed
      to select parameters to assess objects in phthisiology. The system has been
      tested to characterize important sections of phthisiology, such as the
      tuberculosis epidemiological situation and the level of organization of
      tuberculosis-controlling work. Important results have been obtained. The index of
      early recurrences under the present conditions has been found to characterize the
      severity of endemia of tuberculosis rather than the quality of tuberculosis
      controlling work. According to the specific epidemiological situation, childhood
      tuberculosis mortality and morbidity may be epidemiological indices and the
      indices reflecting the quality of tuberculosis-controlling work.

PMID- 16813064
TI  - [Reconsidering evaluation criteria regarding health care research: toward an
      integrative framework of quantitative and qualitative criteria].
AB  - Debate about the relationship between quantitative and qualitative paradigms is
      often muddled and confused and the clutter of terms and arguments has resulted in
      the concepts becoming obscure and unrecognizable. It is therefore very important
      to reconsider evaluation criteria regarding rigor in social science. As Lincoln &
      Guba have already compared quantitative paradigms (validity, reliability,
      neutrality, generalizability) with qualitative paradigms (credibility,
      dependability, confirmability, transferability), we have discuss use of
      evaluation criteria based on pragmatic perspective. Validity/Credibility is the
      paradigm concerned to observational framework, while Reliability/Dependability
      refer to the range of stability in observations, Neutrality/Confirmability
      reflect influences between observers and subjects,
      Generalizability/Transferability have epistemological difference in the way
      findings are applied. Qualitative studies, however, does not always chose the
      qualitative paradigms. If we assume the stability to some extent, it is better to
      use the quantitative paradigm (reliability). Moreover as a quantitative study can
      not always guarantee a perfect observational framework, with stability in all
      phases of observations, it is useful to use qualitative paradigms to enhance the
      rigor in the study.

PMID- 16813065
TI  - [Health practice and total mortality among middle-aged and elderly residents in
      Sukagawa, Japan].
AB  - PURPOSE: The present study aimed to clarify the relationship of total mortality
      with the HPI (health practices index: the additive index of five health
      practices) and lifestyle among elderly residents in a Japanese cohort. METHODS: A
      population-based prospective study was conducted in Sukagawa City of Fukushima
      Prefecture, Japan. Self-administered questionnaires were distributed and
      collected via mail. One-third of the city residents aged 40-69 years and over 70
      years were randomly selected. Baseline surveys were conducted in February 2001
      for the '40-69 cohort' and in July for the 'over 70 cohort'. Among 8746 subjects
      in the '40-69 cohort' and 2718 in the 'over 70 cohort', 5,657 (64.7%) and 2,019
      (74.3%) responded, respectively. The questionnaires consisted of items on
      'Alameda seven health practices' (weight, sleeping, smoking, drinking, breakfast,
      exercise, snacking), medical history, perceived health status, and home bound
      status of the 'over 70 aged cohort'. We followed the younger cohort for 3 years
      and 7 months and the elderly cohort for 3 years and 3 months until the end of
      October 2004, and checked their survival status using a municipal resident
      registry. Analysis of factors associated with total mortality one year after the
      baseline survey employed a simple chi2 test, Kaplan-Meier survival analysis, and
      the Cox proportional-hazards model to compute relative risks (RRs). The HPI was
      the additive index of five health practices: weight, sleeping, smoking, drinking,
      exercise. RESULTS: 1. No significant association was observed between lifestyle
      and total mortality in the '40-69 cohort'. However, there were significant links
      between total mortality in the 'over 70 cohort' and HPI and exercise. 2. The
      Kaplan-Meier curves for the 'over 70 cohort' showed higher survival for the group
      with higher HPI scores. Again, results of the Cox proportional-hazards model
      showed no factor significantly associated with the total mortality of the '40-69
      cohort'. For the 'over 70 cohort', HPI, age, sex, subjective health and
      housebound status were associated. Medical history did not show any significant
      influence. For each of 'the Alameda 7 health practices', exercise was associated
      with all-cause mortality. CONCLUSION: 1. Maintaining good health practices
      improves life prognosis of the elderly. 2. The HPI is an useful indicator of life
      prognosis. 3. Promotion of exercise and prevention of becoming housebound are
      important for improving life prognosis.

PMID- 16813066
TI  - [Development and evaluation of a social isolation prevention program for the
      relocated elderly].

PMID- 16813067
TI  - [Trends in rates of stroke inpatients and proportions of stroke subtypes in Yao
      City, Osaka].

PMID- 16813068
TI  - Effects of atmospheric temperature and pressure on the occurrence of acute
      myocardial infarction in Hiroshima City, Japan.
AB  - In contrast to studies of the effects of atmospheric temperature and pressure on
      the occurrence of acute myocardial infarction (AMI), the interaction of these two
      factors has rarely been studied. We analyzed ambulance data (1993-2002) due to
      AMI in Hiroshima City using the poisson regression model to examine the main
      effects and the interaction of atmospheric temperature and pressure on AMI
      (n=3755). In the analysis, thermohydrological-index (THI), or humidity adjusted
      temperature, was calculated to involve the effect of relative humidity. The
      significant influence of atmospheric temperature on AMI was confirmed. Daily
      events of AMI decreased as temperature increased. Daily events in the low,
      moderate, and high temperature groups were 1.16, 1.07 and 0.90, respectively
      (average=1.03/day). Atmospheric pressure showed a weaker effect in the presence
      of temperature. A more profound interaction was found between temperature and
      pressure. The highest daily events 1.38 were observed in the low temperature and
      low pressure group, while this meteorological type was always accompanied by rain
      and/or snow. It was significant (p=0.047) and 37% higher than that of the high
      temperature and moderate pressure group. The lowest daily events 0.87 were
      observed in the high temperature and low pressure group. These associations were
      reinforced when temperature adjusted by relative humidity was used. Atmospheric
      temperature and the interaction of temperature and pressure had significant
      influences on the occurrence of AMI. The highest risk was found on days with low
      temperature and low pressure. Days with high risk were characterized by winter
      rain and/or snow.

PMID- 16813069
TI  - Evoked spinal cord potentials monitored at thoracoabdominal region after trans
      intercostal stimulation.
AB  - To investigate the feasibility of a novel recording method for trans-intercostal
      evoked spinal cord potentials (Tic-ESCPs) and the properties of the waveforms,
      the potentials were recorded and analyzed in an animal model. In two beagle dogs,
      Tic-ESCPs were recorded at the left twelfth intercostal to fourth lumbar nerves
      following stimulation at the left eleventh intercostal nerve, either with or
      without the use of a muscle relaxant. The amplitude and latency of the Tic-ESCP
      waves were then measured and compared with those of conventional transcranial
      spinal motor evoked potentials (MEPs). Tic-ESCPs could be obtained at any nerve,
      with or without the use of a muscle relaxant. The Tic-ESCP waveform was clear and
      simple, consisting of a small positive (P1) wave and a subsequent large negative
      (N1) wave. As the site of recording moved farther from the stimulation site, the
      N1 amplitudes were reduced and the P1 latency was prolonged. Under muscle
      relaxation, the N1 amplitudes were reduced, and the P1 latencies were shorter. As
      compared with MEPs, Tic-ESCPs could be evoked by a weaker stimulus, the N1
      amplitude was smaller, and the P1 latency was shorter. Tic-ESCP recording was
      feasible either with or without the use of a muscle relaxant. The Tic-ESCPs
      showed simple and clear waveforms with smaller stimulations. Therefore, Tic-ESCPs
      may be useful for intraoperative spinal cord monitoring.

PMID- 16813070
TI  - Lipid-lowering effect of monascus garlic fermented extract (MGFE) in
      hyperlipidemic subjects.
AB  - Monascus Garlic Fermented Extract (MGFE) is a unique material produced from
      garlic fermented using Monascus pilosus, which contains characteristic compounds
      such as dimerumic acid and monacolin K. In this study, we examined the effect of
      MGFE on hyperlipidemic subjects. Fifteen subjects aged 33-59 years (11 men and 4
      women) participated. All the subjects had either hypercholesterolemia (> or = 220
      mg/dl) or hyper-low-density lipoprotein cholesterolemia (> or = 140 mg/dl), but
      only 4 of the 15 (27%) were hypertriglycemic (> or = 150 mg/dl). All subjects
      received two capsules of MGFE (225 mg/capsule) after breakfast and dinner for 4
      weeks. After an overnight fast, blood was taken 0, 2 and 4 weeks after the start
      of MGFE intake, and 2 weeks after MGFE withdrawal. MGFE significantly reduced
      serum total cholesterol (TC) and low-density lipoprotein cholesterol levels 2 and
      4 weeks after the start of MGFE intake as compared with the baseline. Although
      the level of high-density lipoprotein cholesterol (HDL-C) was unaffected at any
      time, the atherogenic index calculated from the value of TC and HDL-C was
      significantly reduced 2 and 4 weeks after the start of MGFE intake. These effects
      of MGFE tended to disappear within 2 weeks after withdrawal. Triglyceride (TG)
      and lipid peroxide levels were not reduced dramatically, but TG levels in
      hypertriglycemic subjects tended to reduce as compared with the baseline value.
      No abnormal changes in blood biochemical parameters or adverse effects were
      observed in any of the subjects. Our present results indicate that MGFE
      attenuates hyperlipidemia, suggesting that MGFE is a potent agent for preventing
      arteriosclerotic diseases.

PMID- 16813072
TI  - [Management of diabetes in the elderly].

PMID- 16813071
TI  - Transrectal ultrasound-guided 10-core biopsy of the prostate for Japanese
      patients.
AB  - To determine the utility of transrectal ultrasound (TRUS)-guided 10-core prostate
      biopsy (sextant plus 4 far lateral cores) for Japanese patients, we compared it
      with the standard sextant for detection of prostate cancer. The study patients
      were 564 consecutive Japanese men (median age 71 years) who underwent 10-core
      biopsy because of PSA values of > or = 2.0 ng/ml at Hiroshima University Hospital
      between March 2000 and December 2004. The overall cancer detection rate for the
      10-core biopsy was 42.6% (240/564), which was significantly higher than the 36.3%
      (205/564) for the standard sextant biopsy (P=0.0330), with a 14.6% (35/240)
      improvement. The 10-core biopsy also detected a significant number of additional
      cancers in the sub-groups of patients with PSA values of 2 to approximately 10
      ng/ml (P=0.0275), a prostate volume of > 20 cc (P=0.0440), or normal findings of
      digital rectal examination (P=0.0304). The 10-core biopsy scheme detected 9.6%
      and 2.1 to approximately 8.3% more cancers than the lateral sextant (apex,
      lateral mid portion, and lateral base) and the probable different combinations of
      8-core biopsy designs, respectively. Compared to the standard sextant biopsy, the
      10-core biopsy did not detect an increased proportion of clinically insignificant
      cancers. There was no severe morbidity, and only 2 patients (0.4%) were briefly
      hospitalized due to high fever. These results show that the TRUS-guided 10-core
      biopsy yields a better prostate cancer detection rate than the 6-core or 8-core
      protocol without severe complications. Therefore, it seems to be practicable for
      Japanese patients.

PMID- 16813073
TI  - [Mitochondrial dysfunctions and age-associated diseases].

PMID- 16813074
TI  - [Care for frail elderly].

PMID- 16813075
TI  - [From gerontological social sciences to social gerontology].

PMID- 16813076
TI  - [Roles of biomedical research in gerontology for aged society].

PMID- 16813077
TI  - [Dentistry supports eating function in the aged].
AB  - As demographic aging continues even today, geriatric dentistry responsive to the
      times must be established. The greatest concern of elderly individuals is health,
      and as dentists, we care for the oral cavity as the gateway to the digestive
      organs. Stated briefly then, I believe that our primary role as dental health
      care providers in an elderly society is to maintain and promote health by
      preventing a decline in eating function. Dentistry up to the present has pursued
      responses to disease. But in an elderly society, a decline in oral function
      accompanying aging is a problem. In other words, consistent with changes in the
      population structure, dentistry in the future should not end with the treatment
      of tooth decay, periodontal disease, or other such dental diseases; rather, it
      must pursue a shift to prevention of age-attendant decline in oral function and
      maintenance of healthy food intake and swallowing functions. Nonetheless,
      dentistry is gradually declining in hospitals that admit elderly individuals.
      While urban dental clinics are regarded as too numerous, dentistry in hospitals
      is disappearing, and the thought of health care settings without dentistry is
      sobering. I believe we must eliminate a troubling situation in which our
      connection to dentistry is severed at a time when we most need dentistry. This
      should be the first step in establishing dentistry for maintenance of eating
      functions.

PMID- 16813078
TI  - [The location of living and gerontology].

PMID- 16813079
TI  - [Medicine and society of aging].

PMID- 16813080
TI  - [Opinion from a buddiest priest].

PMID- 16813081
TI  - [End-of-life care at home and the visiting nursing service].

PMID- 16813082
TI  - [Therapeutic strategies including vaccination].

PMID- 16813083
TI  - [Psychotherapy with the cognitive impaired elderly].

PMID- 16813084
TI  - [Effects of rehabilitation in patients with dementia in rehabilitation hospital].

PMID- 16813085
TI  - [Care given to people with dementia in group-home: its merits and problems].

PMID- 16813086
TI  - [Promotion of Alzheimer' s disease programs].

PMID- 16813087
TI  - [Regenerative medicine in cardiovascular system].

PMID- 16813088
TI  - [Regenerative medicine for skin].
AB  - Tissue engineering is moving rapidly from fundamental research to commercial
      applications. The first product is an autologous cultured epidermal substitute.
      Other representative products are allogeneic cultured dermal substitute and
      allogeneic cultured skin substitute. Surgical closure with auto-skin grafting is
      the gold standard for treatment of victims with extensive deep skin defects.
      Therefore, the tissue engineers have to develop the cultured skin substitutes,
      taking into account the successful application of auto-skin grafting, Kuroyanagi
      developed an allogeneic cultured dermal substitute, which was composed of a 2
      layered spongy matrix of hyaluronic acid and atelo-collagen containing
      fibroblasts. This product is able to release a number of biologically active
      substances that are necessary for wound healing. A multi-center clinical study on
      the use of this product has been performed at 30 hospitals across Japan as the
      Regenerating Medical Millennium Project of the Ministry of Health, Labor and
      Welfare.

PMID- 16813089
TI  - [Neuro-regenerative medicine by transplantation of stem cells].

PMID- 16813090
TI  - [Regenerative medicine in the orthopaedic field].

PMID- 16813091
TI  - [Regenerative medicine for bone using mesenchymal stem cells].

PMID- 16813092
TI  - [Klotho gene and endothelial function].
AB  - The klotho gene, originally identified by insertional mutagenesis in mice,
      suppresses multiple aging phenotypes (e.g. arteriosclerosis, pulmonary emphysema,
      osteoporosis, infertility, skin atrophy). We have demonstrated that mice
      deficient for the klotho gene show endothelial dysfunction as manifested by an
      attenuated response of aortic relaxation in response to acetylcholine
      stimulation. Systemic nitric oxide production was also significantly reduced in
      klotho deficient mice. Oxidative stress was increased in klotho deficient mice.
      The klotho gene delivery improves multiple aging phenotypes. Our findings
      establish the basis for the therapeutic potential of klotho gene delivery in age
      related diseases.

PMID- 16813093
TI  - [Cell adhesion and endothelial function in aging and atherosclerosis].

PMID- 16813094
TI  - [Antisenescence as a novel therapeutic strategy for vascular aging].
AB  - Vascular cells have a finite lifespan when cultured in vitro and eventually enter
      an irreversible growth arrest state called "cellular senescence." It has been
      reported that many of the changes in senescent vascular cell behavior are
      consistent with the changes seen in age-related vascular diseases. Recently,
      senescent vascular cells have been demonstrated in human atherosclerotic lesions
      but not non-atherosclerotic lesions. Moreover, these cells express increased
      levels of proinflammatory molecules and decreased levels of endothelial nitric
      oxide synthase, suggesting that cellular senescence in vivo contributes to the
      pathogenesis of human atherosclerosis. One widely discussed hypothesis of
      senescence is the telomere hypothesis. An increasing body of evidence has
      established the critical role of the telomere in vascular cell senescence. More
      recent evidence suggests that telomere-independent mechanisms are implicated in
      vascular cell senescence. Activation of Ras, an important signaling molecule
      involved in atherogenic stimuli, induces vascular cell senescence and thereby
      promotes vascular inflammation in vitro and in vivo. Constitutive activation of
      Akt also induces vascular cell senescence. This novel role of Akt in regulating
      the cellular lifespan may contribute to various human diseases including
      atherosclerosis and diabetes mellitus. Although a causal link between vascular
      aging and vascular cell senescence remains elusive, a large body of data is
      consistent with cellular senescence contributing to age-associated vascular
      disorders. This review considers the clinical relevance of vascular cell
      senescence in vivo and discusses the potential of antisenescence therapy for
      human atherosclerosis.

PMID- 16813095
TI  - [Effects of FOXO1-deficiency on the development of the vascular system].

PMID- 16813096
TI  - [Home end-of-life care for advanced dementia vs advanced cancer elderly patients:
      dying elderly at home project].
AB  - AIM: The aim of this study was to assess the frequency of symptoms and end-of
      life care received in advanced dementia and advanced cancer elderly patients
      dying at home during the last two days of their lives and to evaluate the
      differences observed between the two groups. METHODS: We used data from the Dying
      Elderly at Home (DEATH) project, which was a prospective study of home elderly
      patients dying with end-stage illness. Consecutive deceased subjects aged 65 or
      older who were seen at 16 study clinics belonging to the Japanese Society of
      Hospice and Home-care with diagnoses of all illnesses including advanced dementia
      and advanced cancer and died at home from October 2002 to September 2004 were
      included in the study. We evaluated 36 deceased subjects with advanced dementia
      and 116 with advanced cancer. We collected the following information:
      sociodemographics, ADLs, cognitive impairment, observed symptoms and end-of-life
      care provided during the last 48 hours of life. RESULTS: Deceased subjects with
      advanced dementia were less likely to show symptoms of pain, acute confusion, or
      nausea/vomiting and more likely to display fever or cough than advanced cancer
      patients. Also, those with advanced dementia were more likely to receive
      intravenous drip injection or narcotic analgesia and more likely to be given
      sputum suction, or antibiotics. CONCLUSION: We observed that the dying process
      and end-of-life care for advanced dementia elderly patients was different from
      that for advanced cancer elderly patients.

PMID- 16813097
TI  - [Nourishment of patients with persistent disturbance of consciousness and
      nutritional markers to simplify evaluation].
AB  - AIM: This study was aimed to evaluate the nourishment of patients with a
      disturbance of consciousness who received tube feeding, and to discuss
      nutritional markers to simplify evaluation in these patients at home or at
      facilities for the elderly. METHODS: The nourishment of 46 patients with a
      disturbance of consciousness who received tube feeding was evaluated by
      performing 1) physical measurements, 2) blood test, and 3) measurement of resting
      metabolic rate. Furthermore, the anemia-like symptoms of the palpebral
      conjunctiva, which were supposed to be related with nourishment, were
      subjectively evaluated to clarify their relevance to the results of physical
      measurements and blood test. RESULTS: The average of triceps skinfold thickness
      (%TSF), which shows relative physical measurement data of patients with a
      disturbance of consciousness when compared to those of healthy people, was 105.7
      +/- 39.8, which was almost equivalent to that of healthy people. The arm muscle
      circumference (%AMC) and calf circumference (%CC) were 87.5 +/- 11.5 and 73.6 +/-
      9.4, respectively. In the blood test, the average Alb value was 3.3 +/- 0.5 g/dl,
      suggesting that 35 (76.1%) of the 46 patients with disturbance of consciousness
      had protein energy malnutrition (PEM). Since the relationship between anemia-like
      symptoms of the palpebral conjunctiva and Hb/Ht (p < 0.01, p < 0.01) and Alb (p <
      0.05) was confirmed, there is a high possibility that these markers can be useful
      for easy evaluation of nourishment. CONCLUSION: Because hypoalimentation is a
      more serious problem than overnutrition in patients with a disturbance of
      consciousness, we consider that the calorie count should be adjusted based on the
      measurement results of resting energy expenditure (REE) in individual patients,
      although the count for patients with tube feeding was set at individual levels of
      basal metabolism in the conventional method. Moreover, further discussion is
      required regarding alternative markers for nutritional evaluation to blood test
      data.

PMID- 16813098
TI  - [Short and long-term changes in physical functions in the elderly in relation to
      comprehensive geriatric training].
AB  - AIM: The purpose of the present study was to investigate the changes of physical
      functions of subjects who participated in a progressive resistance and balance
      training program named Comprehensive Geriatric Training (CGT) before and after
      training, and following lyear. METHODS: Sixty-three community-dwelling elderly
      participated in CGT. Subject's physical functions (muscle strength, balance,
      walking speed) were measured. Moreover, we interviewed the subjects about their
      maintenance of exercise after training. RESULTS: Fifty-five subjects completed
      CGT, and physical functions were measured in 32 subjects. There were significant
      differences in all physical functions. In the post-hoc test, there were
      significant differences between before and after one year (one leg standing with
      open eyes, flexibility, functional reach, maximum walking speed, timed up and
      go). Of the 32 subjects, 21 kept training 1 or more days per week after training
      (TR), but 11 were desisted from training (DT). Between the 2 groups, the main
      effect at Group, Time, Group x Time interaction were significant with Functional
      Reach. It was significantly improved after 1 year compared with before training
      in TR. No physical functions in after 1 year were significantly lower than before
      training. CONCLUSION: The subjects improved, maintained the physical functions
      through CGT. Moreover, the physical functions after 1 year did not decrease
      significantly compared to before CGT. It is possible that this program controlled
      the decrease in physical functions at one year. This program provided an
      opportunity to begin and continue exercise training, because more than half of
      the subjects who did not previously exercise regularly continued resistance
      training.

PMID- 16813099
TI  - [Nutritional risk in community-dwelling elderly long-term care insurance
      recipients].
AB  - AIM: To define degree of nutritional risk in community-dwelling older disabled
      adults using translated Nutrition Screening Initiative (NSI) checklist and to
      identify important underlying factors associated with high nutritional risk.
      METHODS: Community-based studies were conducted in Katsushika, Tokyo and Odate
      and Tashiro, Akita. A total of 695 and 381 older adults, respectively, designated
      for long-term care insurance were interviewed. Nutritional risk was measured
      using the Japanese-translated NSI checklist. Demographic information, ADL, IADL,
      MMSE, CES-D, PGC morale scale, self-perceived health, loneliness, perceived
      caregiver's care burden, relationship with caregiver, perceived inadequacy of
      income, perceived burden of care cost were assessed using standardized
      instruments. RESULTS: Self-perceived health strongly related to high NSI score in
      both areas. Nutritional risk was considered 'high' when simply added NSI score
      was 3 points and over (NSI-10) and weighed NSI score was 6 points and over (NSI
      21). Logistic regression analysis demonstrated that high levels of depression
      symptoms, poor self-perceived health, female and area (Odate/ Tashiro) were
      associated with NSI-10-based high risk and high levels of depression symptoms,
      smaller family member, perceived inadequacy of income and area (Odate/Tashiro)
      were associated with NSI-21-based high risk. These results were completely same
      when CES-D scores were replaced with PGC morale scale scores. CONCLUSION: It is
      concluded that emotional well-being is the important factor for maintaining
      nutritional environment in community-dwelling disabled older adults.

PMID- 16813100
TI  - [Health-related quality of life factor in chronic hemodialysis patients].
AB  - AIM: The purpose of this study was to investigate the related factors of the
      health-related quality of life (HRQOL) measured by KDQOL-SF version 1.3 Japanese
      version) in chronic hemodialysis patients. METHODS: Using a cross-sectional
      survey design, we hand-delivered a self-administered questionnaire to the chronic
      hemodialysis patients and finally obtained 67 subjects' data to analyze. The
      response rate was 65.7%. Among the related factors, disease/dialysis-related
      factors and rehabilitation-related factors in addition to demographic factors
      were examined. The HRQOL was divided into a physical component summary (PCS) and
      a mental component summary (MCS). RESULTS: Multiple linear regression analysis
      revealed that the independent factors related to PCS were symptom score, serum
      albumin level, patients' satisfaction with dialysis care, and the work status.
      These four factors could explain 60% of PCS variance (adjusted R2 = 0.601). The
      independent factors related to MCS were revealed to be quality of social
      interaction and understanding of effectiveness of self-exercise. These two
      factors could explain only a quarter of MCS variance (adjusted R 2 = 0.223).
      CONCLUSION: These results suggest that highly satisfactory care of dialysis,
      improvement of dialysis-related symptoms, and good nutritional management are
      important for improving HRQOL in chronic hemodialysis patients, and that the
      promotion of social participation and interpersonal relationships as well as a
      positive attitude to self-exercise may lead to a beneficial outcome of
      rehabilitation for chronic hemodialysis patients.

PMID- 16813101
TI  - [Effectiveness of ability grouping in structured fall prevention exercise program
      for frail elderly people].
AB  - AIM: To assess the effectiveness of ability grouping in a fall prevention
      structured exercise program for elderly people. METHODS: We enrolled 124 subjects
      from among 2,582 elderly people aged 70 to 84 years living in the Tsurugaya
      district in Sendai City. Exclusion criteria were 1) motor fitness scale (MFS)
      score 9 points or more, 2) severe sensory, cognitive, or 3) physical disorders,
      and 4) nursing care grade 2 or more. Those ranked in the lower fourth and in the
      upper 3 fourths of the timed up and go test (TUGT) were each randomly assigned to
      3 groups. Subjects in groups A and B had an exercise program for lower and higher
      fitness subjects separately, whereas all subjects in group C underwent a single
      exercise program. The exercise program, once a week for 12 weeks, consisted of
      strength and stability training. TUGT, lateral reach (LR), leg power per body
      weight and MFS were measured after the intervention and compared with the
      baseline values. RESULTS: There were no difference in the baseline
      characteristics among the groups. For group A, no significant changes in physical
      fitness measures, for group B a small but significant deterioration in LR, and
      for group C a small but significant deterioration in LR and TUGT were observed.
      MFS score improved significantly in all groups. CONCLUSION: Ability grouping
      appeared to be effective for a short-term exercise program in maintaining the
      physical ability, but the effectiveness did not reach statistical significance in
      the randomized controlled design.

PMID- 16813102
TI  - [Relation between the level of care needed and frailty for labial functions].
AB  - AIM: The purpose of this study was to examine whether the improvement of oral
      functions could prevent increase in the level of care needed in the elderly by
      analyzing the relationship between the level of care needed and labial functions.
      METHODS: The subjects were 114 elderly people who were healthy or needing care
      (44 men, 70 women; average age 81.3 +/- 6.3 years), all of whom maintained
      posterior occlusal support with their natural dentition and had no defect in
      front teeth. They were divided into four groups; Group 1: healthy elderly, Group
      2: elderly requiring assistance or Care Category 1, Group 3: elderly requiring
      Care Categories 2 and 3, Group 4: elderly requiring Care Categories 4 and 5,
      according to the classification of certification of eligibility for long-term
      care by the Japanese Ministry of Health, Labor and Welfare. Water-repellent
      pressure sensors (PS-2KA, Kyowa Electric Co, Japan) were embedded in an acrylic
      plate. The device was used to measure the labial-closing pressure during 1-gram
      yogurt ingestion, the maximum labial pressure with effort and the reserve
      capacity of pressure. Drooling of food as feeding/swallowing dysfunction of the
      subjects was surveyed. RESULTS: 1) The mean value of labial pressure with effort
      was 296.4 +/- 153.9 Pa, and that of the reserve capacity of labial pressure was
      209.6 +/- 152.3 Pa. They showed significant declines in accordance with the
      aggravation level of needing care (p < 0.01). 2) The labial pressure with effort
      and the reserve capacity of pressure in subjects who showed drooling of food
      symptom were significantly lower compared to those who showed no drooling of food
      symptom (p < 0.05). CONCLUSION: Labial functions declined in accordance with the
      increased level of care needed, and a relationship between drooling of food and
      labial-closing pressure was recognized. It was suggested that the improvement of
      labial functions might prevent increased need of care.

PMID- 16813103
TI  - Flow dynamic comparison of in-situ internal thoracic and gastroepiploic arterial
      conduits: experimental study.
AB  - OBJECTIVE: We tried to experimentally clarify the flow dynamic differences under
      flow competitive conditions between the internal thoracic artery (ITA) and
      gastroepiploic artery (GEA) as in-situ arterial bypass conduits. METHODS: The ITA
      and the GEA were anastomosed close together to the left anterior descending
      artery (LAD) in 8 pigs. Flow characteristics of the ITA and the GEA were analyzed
      using a transit time flowmeter under the following flow competitive conditions;
      condition A: the ITA, GEA and LAD were left open, condition B: either of the ITA
      or GEA were clamped and the LAD was left open, condition C: the ITA and GEA were
      open but the proximal LAD was clamped, condition D: either of the ITA or GEA were
      clamped and the proximal LAD was also clamped. RESULTS: The flow volume of the
      ITA was significantly (p<0.001) greater than that of the GEA in condition A (27
      +/- 11 ml/min vs. -4 +/- 9 ml/min), B (26 +/- 17 ml/min vs. -1 +/- 14 ml/min) and
      C (38 +/- 14 ml/min vs. 0 +/- 4 ml/min), but did not differ (p=0.685) in
      condition D (29 +/- 6 ml/min vs. 31 +/- 14 ml/min). Retrograde flow in systole
      and antegrade flow in diastole was seen in the GEA in condition A, B and C.
      CONCLUSION: Under flow competitive conditions, flow of the GEA was inferior to
      that of the ITA. These data suggested that the GEA is more sensitive to
      competitive flow than the ITA. This may be due to anatomical differences between
      these in-situ bypass conduits.

PMID- 16813105
TI  - Leiomyoma originating from the extrapleural tissue of the chest wall.
AB  - We describe a rare case of leiomyoma of the chest wall in a 55-year-old female.
      Computed tomography showed a well-circumscribed neoplasm with a diameter of 2 cm
      in the right chest wall. The tumor was excised with video-assisted thoracic
      surgery. Histopathology confirmed that the tumor was leiomyoma arising from the
      microvascular smooth muscle in the chest wall. We present the immunohistochemical
      profiles of the tumor in detail, critically reviewing the previously reported
      cases.

PMID- 16813104
TI  - Aortic valve replacement with a 16-mm CarboMedics valve in adult patients.
AB  - Management of the small aortic root is a significant problem for the surgeon with
      regard to operative technique and selection of the prosthesis. We report on four
      adults with a small aortic root who underwent aortic valve replacement with a 16
      mm CarboMedics bileaflet valve. All patients now lead normal lives. Postoperative
      Doppler measurements demonstrated an acceptable transprosthetic gradient.

PMID- 16813107
TI  - Systolic anterior motion of the mitral valve despite the sliding leaflet
      technique for repair of the mitral valve.
AB  - We report a systolic anterior motion of the anterior mitral leaflet despite
      employing the sliding leaflet technique for repair of mitral valve regurgitation.
      A 65-year-old man with chronic, symptomatic mitral regurgitation due to ruptured
      chordae tendineae underwent mitral valve repair by quadrangular resection of the
      posterior leaflet and sliding leaflet technique with ring annuloplasty. After
      weaning from cardiopulmonary bypass, left ventricular outflow obstruction
      developed and transesophageal echocardiography demonstrated systolic anterior
      motion of the mitral valve and severe mitral regurgitation. Non-operative
      treatment resolved the outflow tract obstruction, systolic anterior motion and
      mitral regurgitation. We conclude that post-repair systolic anterior motion can
      still occur after the sliding plasty procedure and that medical treatment can
      successfully resolve systolic anterior motion and outflow tract obstruction in
      most patients.

PMID- 16813106
TI  - Infective endocarditis with an aortic periannular abscess extending along the
      right coronary artery.
AB  - A 50-year-old male underwent surgery for infective aortic valve endocarditis,
      which had been refractory to medical treatment. The valve was bicuspid, and
      involvement of the annular and subannular structures was recognized. A large
      suppurative discharge was obtained on incising this portion. Although there was
      no interventricular shunt, the abscess cavity was revealed to extend through the
      epicardial surface of the right atrioventricular groove. Following extensive
      debridement and irrigation, the defect was closed by an autologous pericardial
      patch. A 23 mm mechanical valve was implanted placing some of the stitches deep
      into the muscular interventricular septum. Infection was controlled by six-week
      administration of cefazolin sodium and gentamicin sulfate, and the patient
      survived.

PMID- 16813108
TI  - Revascularization using satellite vein after radial artery harvested for coronary
      artery bypass grafting.
AB  - The radial artery has been increasingly used for coronary artery bypass grafting
      and has excellent long-term patency rates. Hand claudication is one of the
      adverse effects after radial artery harvest. We reconstructed a radial artery
      using the satellite vein to prevent hand claudication. Pulsating blood flow at 35
      cm/sec was evaluated using color Doppler echocardiography three months after
      surgery. This method makes it possible to use a radial artery in patients with a
      positive Allen test.

PMID- 16813109
TI  - Large cell neuroendocrine thymic carcinoma coexisting within large WHO type AB
      thymoma.
AB  - Large cell neuroendocrine carcinoma (LCNEC) is a rare type of thymic epithelial
      tumor. It is recognized as a different entity from other thymic tumors on account
      of it having a more aggressive biologic behavior and poor prognosis. We report an
      extremely rare case of a very small, "large cell neuroendocrine thymic carcinoma"
      coexisting within a large thymoma that could not be detected by usual biopsy.
      Surgery as the initial treatment has the significance of definitive diagnosis and
      curative treatment for LCNEC of the thymus. To make a successful differential
      diagnosis, application of detailed immunohistochemical stains may be of aid,
      since thymic epithelial tumor is not always morphologically homogenous.

PMID- 16813110
TI  - Anomalous origin of the right coronary artery from the pulmonary artery.
AB  - A case of anomalous origin of the right coronary artery from the pulmonary artery
      in a 73-year-old man is presented. The patient had been suffering from chronic
      heart failure with mitral and tricuspid regurgitation and atrial fibrillation for
      two years. Surgical repair was performed successfully, including ligation of the
      right coronary artery and coronary arterial bypass with a radial artery graft.

PMID- 16813111
TI  - Resected case of synovial sarcoma in the pleural cavity.
AB  - A 29-year-old female was admitted to our hospital complaining of severe dry cough
      and low-grade fever. A chest roentgenogram and a chest computed tomographic scan
      revealed a huge tumor and massive pleural effusion in the left pleural cavity.
      Pathological examination revealed spindle shaped malignant cells. SYT-SSX fusion
      gene transcripts were detected, so we diagnosed the tumor as a synovial sarcoma
      in the pleural cavity. After neoadjuvant chemotherapy we resected the tumor
      completely. A synovial sarcoma in the pleural cavity is extremely rare. To the
      best of our knowledge, this is the thirteenth case, and the first case to undergo
      neoadjuvant chemotherapy and complete resection. Because a synovial sarcoma in
      the pleural cavity has a poor prognosis and is characterized by a high incidence
      of recurrence, we must carefully follow up this patient.

PMID- 16813112
TI  - 34 pieces of advice worth repeating.

PMID- 16813113
TI  - Reinventing the specialty.

PMID- 16813114
TI  - Reinventing the specialty.

PMID- 16813115
TI  - Reinventing the specialty.

PMID- 16813116
TI  - Reinventing the specialty.

PMID- 16813117
TI  - Reinventing the specialty.

PMID- 16813118
TI  - Researchers examine what makes a small medical group exemplary.

PMID- 16813119
TI  - New drugs: how to decide which ones to prescribe.

PMID- 16813120
TI  - Improve your ICD-9 coding with voice-recognition macros.

PMID- 16813121
TI  - Precertification, denials and appeals: reducing the hassles.

PMID- 16813122
TI  - Getting off the collections treadmill.

PMID- 16813123
TI  - Don't be a target for a malpractice suit.

PMID- 16813124
TI  - Dressed to ill.

PMID- 16813125
TI  - [Viral influenza: a public health problem].

PMID- 16813126
TI  - [Maternal mortality in Guatemala: differences between hospital and non-hospital
      deaths].
AB  - OBJECTIVE: To estimate the association between obstetric and socio-demographic
      characteristics and risk factors related to intra- and extra-hospital maternal
      mortality in Guatemala during the year 2000. MATERIALS AND METHODS: A cross
      sectional epidemiologic study was carried out in 649 maternal mortality (MM)
      cases that occurred in Guatemala during 2000, comparing characteristics of intra-
      and extra-hospital maternal deaths. Multivariate statistical analysis was
      conducted using Stata 7.0 software. RESULTS: Out of 649 registered MM cases, 270
      (41.6%) were classified as intra-hospital MM and 379 (58.4%) as extra-hospital
      MM.A larger proportion of deaths occurred in women over 35 years of age (29.28%),
      those of indigenous ethnicity (65.49%), married or cohabiting (87.83%),who had
      unpaid employment (94.78%), and without formal education (66.56%). Compared with
      intra-hospital MM cases,the risk of extra-hospital MM was greater among
      indigenous women (OR 3.4; CI 95% 2.8-5.3),those who had unpaid employment (OR
      8.95; CI 95% 1.7-46.4), a low level of formal education (OR 1.96; CI 95% 1.0-3.8)
      and hemorrhaging as the immediate cause of death (OR 4.28; CI 95% 2.3-7.9).
      CONCLUSIONS: Although some characteristics of intra- and extra-hospital MM cases
      are similar, a greater proportion of deaths were extra-hospital. This could be
      related to the high percentage of the population that lives in rural or
      marginalized areas, which in addition to certain cultural aspects (related to the
      fact that most of the population is indigenous) may impede access to health
      services. The results of this study can be useful for determining intervention
      strategies to prevent maternal mortality in intra- and extra-hospital contexts in
      Guatemala.

PMID- 16813127
TI  - [Hyperlipidemia and glucose intolerance in patients with HIV infection receiving
      antiretroviral therapy].
AB  - OBJECTIVE: To determine the prevalence of secondary effects on lipid metabolism
      as a result of highly active antiretroviral therapy (HAART), as well as the
      impact of different types of antiretroviral regimens on lipids and glucose in a
      group of patients in Yucatan, Mexico. MATERIAL AND METHODS: A cross-sectional
      study was conducted. A questionnaire created for this study was administered to
      each patient and total cholesterol, triglycerides and fasting glucose values were
      determined. The presence of hyperlipidemia and alterations in glucose were
      determined as well as their relation to the epidemiological variables obtained
      from the questionnaire. RESULTS: A total of 211 subjects were studied [36 (17%)
      of which were women and 175 (83%) men]. Ninety-two patients (44%) were found to
      have hyperlipidemia. Of these, 43 (20%) had hypercholesterolemia (HC) and 82
      (39%) hypertriglyceridaemia (HT). The presence of combined HC and HT was observed
      in 30 (14%) patients. Nineteen (9%) patients had alterations in glucose, six (3%)
      diabetes mellitus and 13 (6%) impaired glucose tolerance. The variables
      associated with the presence of hyperlipidemia were: levels of lymphocytes CD4
      >350 cells/microl (OR = 2.79 1.08-7.27, p = 0.03), male gender (OR = 3.6 1.4
      9.12, p = 0.006) and the use of nucleoside-reverse transcriptase inhibitors
      (NRTI) (OR = 3.1 1.2-8.1, p = 0.01). CONCLUSIONS: Patients with HIV infection who
      receive HAART have an increased risk of presenting hyperlipidemia. In this group
      of patients the presence of hyperlipidemia and impaired glucose tolerance was
      significant. Unlike what has been indicated in most published reports, the
      alterations of lipids were associated more frequently with INTR use, for which it
      is concluded that the pathogeny of these alterations is not unique, that it is
      probable that concurrent effects exist between different antiretroviral drug
      families and that other host factors are involved in the pathogenic mechanism of
      these alterations.

PMID- 16813128
TI  - [Adaptation and validation of quality of life instrument Diabetes 39 for Mexican
      patients with type 2 diabetes mellitus].
AB  - OBJECTIVE: To adapt and validate the Spanish language version of the Diabetes 39
      instrument, which measures quality of life,for Mexican patients with type 2
      diabetes mellitus (DM-2). MATERIALS AND METHODS: The Spanish language version of
      the instrument was adapted to make it more comprehensible to Mexican patients. In
      a cross-sectional survey, the instrument was administered on two different days
      to 260 patients with type DM-2. Glycated hemoglobin (HbAic), total cholesterol,
      triglycerides, blood pressure, body mass index and waist/hip ratio were measured.
      Information about age, sex, time since diagnosis of diabetes, diabetes related
      complications and comorbidity was obtained. RESULTS: A total of 249 subjects
      completed the study, 62.7% of which were women. Cronbach's alpha coefficient was
      > or = 0.80 for the domains and 0.95 for the total score. The test-retest
      consistency for the total score was r = 0.82, p = 0.01. The median of the total
      score was 29 (on a scale of 0-100), which was considered the cutoff value for
      defining "better" (<29) and "worse" > or =29) quality of life.A worse quality of
      life was associated with diabetes related complications > or =1 (OR = 1.73; IC
      95% 1.05-3.06); total cholesterol >240 mg/dL (OR = 4.43; IC 95% 1.23-16.26);
      comorbidity > or =2 diseases (OR = 2.36; IC 95% 1.31-4.28); diabetes longer than
      10 years (OR = 2.19; IC 95% 1.2-3.78), and HbA(IC) >8% (OR = 1.81; IC 95% 1.09
      2.99). The last three were identified as predictor variables for worse quality of
      life by logistic regression (p < 0.05). CONCLUSIONS: The adapted Spanish language
      version of Diabetes 39 is a reliable and valid instrument for measuring the
      quality of life of Mexican patients with DM-2.

PMID- 16813129
TI  - [Lead levels in high-risk populations and the surrounding environment in San
      Ignacio, Fresnillo, Zacatecas, Mexico].
AB  - OBJECTIVE: To determine the lead concentration in the blood of children and
      nursing or pregnant women from San Ignacio, Fresnillo, in Zacatecas, Mexico as
      well as in soil, plants, ash and lead-glazed pottery, in order to determine
      exposure due to a metal-recycling facility. MATERIAL AND METHODS: The study was
      carried out from December 2004 to April 2005. Lead in blood was measured with
      anodic stripping voltammetry, while dispersive energy X-ray fluorescence was used
      in the other matrices. RESULTS: Based upon the criteria outlined in the Official
      Mexican Standards, 90% of the children was identified as category 1, 5% as
      category II and another 5% as category III. The soil in the land near the
      facility contained from 73 to 84,238 microg/g, with an average of 4940 microg/g.
      Larger lead concentrations were found on sites located closer to the facility.
      San Ignacio's soil contained, on average, 109 microg/g. High lead levels were
      found in glazed pottery and the concentration in agricultural crops was greater
      than 300 microg/g. CONCLUSIONS: Although the majority of children in San Ignacio
      have blood lead concentrations considered to be acceptable according to the
      Official Mexican Standards, several studies indicate that deleterious effects on
      children's health exist even at low concentrations. The land around the metal
      recycling facility is contaminated with lead, and to that extent, the crops that
      are produced there, once ingested, are a source of contamination, which is
      compounded by the use of glazed pottery.

PMID- 16813130
TI  - [Prevalence of dengue and leptospira antibodies in the state of Veracruz,
      Mexico].
AB  - OBJECTIVE: To discover the prevalence of antibodies against denguevirus and
      leptospira. MATERIAL AND METHODS: A cross-sectional study was carried out in 500
      inhabitants of Veracruz, Mexico through household sampling, administration of a
      questionnaire and collection of blood samples.The presence of IgG antibodies was
      determined and factors associated with seroprevalence were evaluated using a
      logistic regression model. RESULTS: Total denguevirus seroprevalence was 79.6%
      (IC 95% 76-81). The main factors associated with infection were age and residence
      in neighborhoods with higher vectorial indices (RMP = 2.94, IC 95% 1.46-6.1).
      Overall seroprevalence against leptospira was 4% (IC 95% 2-6). Prevalence was
      higher in the 25 to 44 years age group (35%, IC 95% 15-59). Seroprevalence in
      individuals who referred to living with dogs, pigs, cows and rats was 25% (IC 95%
      0.63-80). Eighty-five percent of individuals who were leptospira positive were
      also dengue positive. CONCLUSIONS: The prevalence of denguevirus antibodies
      suggests the risk of serious dengue hemorrhagic outbreaks. Although leptospirosis
      prevalence was low, the coexistence of both agents was confirmed.

PMID- 16813131
TI  - [Integral analysis of the pedagogical practices of an educational program in
      Colombia].
AB  - OBJECTIVE: To present a portion of a study aimed at evaluating the effects and
      impact of education and processes explained from the actors' point of view and
      relating to an educative proposal that is based on knowledge dialogues from the
      Growth and Development Program in the city of Medellin, Colombia. MATERIAL AND
      METHODS: An evaluative, multiple case research study was carried out. RESULTS:
      Among the study results is the finding that, even though health educators were
      familiar with and committed to the educative process, they applied pedagogical
      practices that were related to the pedagogical model they wanted to change. This
      constitutes the theme of this article. CONCLUSIONS: These results are explained
      using an ecological model that contains three levels: context, rationality and
      pedagogical practices. The transformation of the educator is identified as a
      central element in health education based on a different paradigm, as well as the
      complexity of such transformation.

PMID- 16813132
TI  - Cervical cancer and the HPV link: identifying areas for education in Mexico
      City's public hospitals.
AB  - OBJECTIVE: To assess Mexico City physicians' knowledge and practices regarding
      cervical cancer and human papillomavirus (HPV) to compare
      obstetricians/gynecologists (ob/gyns) and general practitioners (GPs) on these
      variables. MATERIAL AND METHODS: In April 2003, 187 ob/gyns and GPs working in 15
      hospitals affiliated with the Federal District Secretary of Health (SSDF)
      completed a self-administered questionnaire. Pearson's chi-square tests were used
      to compare ob/ gyns and GPs on outcome variables. RESULTS: Nearly all providers
      (93%) identified HPV as the principal cause of cervical cancer. Ob/gyns had more
      detailed knowledge about HPV than GPs and were more likely to have heard of
      common oncogenic strains (p = .000). Sixteen percent of all physicians
      incorrectly stated that Pap tests should be performed every six months regardless
      of previous results, and 17% recommended hysterectomy as an option for treating
      mild or moderate dysplasia. CONCLUSIONS: While SSDF physicians had basic
      knowledge about the cervical cancer-HPV link, screening and management norms are
      priority areas for educational interventions.

PMID- 16813133
TI  - [Influenza, an existing public health problem].
AB  - Seasonal influenza is an acute and recurring respiratory disease known since
      ancient times, occuring, in particular, during winter months and having an
      elevated effect on public health worldwide. The disease has high morbidity rates
      for people of all ages and particularly high mortality rates for children, adults
      over 60 years old, patients with chronic illnesses and pregnant women. Prevention
      control strategies include vaccination using inactivated, subunit or genetically
      modified virus vaccines. Influenza in humans is caused by two subtypes of
      influenza virus A and one of influenza virus B. The influenza virus A that
      affects humans mutates easily, thereby often causing new antigenic variants of
      each subtype to emerge, requiring the inclusion of such variants in annual
      vaccines in order to assure proper immunization of the population. The influenza
      pandemic refers to the introduction and later worldwide spread of a new influenza
      virus in the human population, which occurs sporadically. Due to the lack of
      immunity in humans against the new virus, serious epidemics can be provoked
      resulting in high morbidity and mortality rates. Historically, influenza
      pandemics are a result of the transmission of the virus from birds to humans, or
      the transfer of such genes to seasonal influenza. Wild waterfowl--both migratory
      and shore birds--carry a large diversity of influenza virus subtypes, which are
      eventually transmitted to domestic birds. Some of those viruses cross the species
      barrier and infect mammals, including humans. The adaptation process of the avian
      virus to mammal hosts requires time. Therefore, the presentation of these cases
      can take several years. Since December 2003, in several Southeast Asian countries
      a large proportion of domestic birds have been affected by an avian influenza
      epidemic (subtype H5N1). By Februrary 2006, the epidemic had already affected
      countries in Europe and Africa, having a significant economic impact on
      commercial poultry due to the more than 180 million birds that were sacrificed.
      Some strains of this avian influenza virus have directly, although incipiently,
      infected the human population. The virus has not yet acquired with complete
      efficiency person-to-person infection and transmission, which has limited its
      spread among humans. Since the mortality rate in infected individuals is greater
      than 50%, the World Health Organization (WHO) called on their member countries to
      establish preparation and emergency plans against the threat of a possible
      pandemic associated with H5N1 virus, or another virus related to common
      influenza. These actions are intended to prevent or reduce the impact of the
      threat, as experienced in previous pandemics, such as in 1918 when roughly 40
      million people died worldwide. The prevention and control plans include, among
      other strategies, vaccination and antiviral medications. Nevertheless, to date
      there are no vaccines to be administered to the population in the case of a new
      influenza pandemic emergency and it is possible that countries that produce the
      annual seasonal influenza vaccine lack the capacity to produce the pandemic virus
      vaccine in a short period of time. In addition, recent studies have identified
      the existence of influenza virus strains resistant to common antiviral agents.
      The purpose of this review is to update the basic concepts of influenza in order
      to strengthen epidemiological surveillance of the disease and reinitiate
      prevention and control actions in the event of a pandemic.

PMID- 16813134
TI  - [The next pandemic?].

PMID- 16813135
TI  - [Preparing for the next pandemic].

PMID- 16813136
TI  - Perception of oral health among adults in Karachi.
AB  - PURPOSE: To survey an adult population in a deprived district of Karachi, with
      special reference to perceived oral health. MATERIALS AND METHODS: One thousand
      questionnaires, covering topics such as socioeconomic status, general health and
      oral health were distributed to the participants' homes by dental auxiliaries,
      and 994 were returned. The respondents were adults aged between 30 and 50 years.
      Women comprised 49% of the sample. RESULTS: Over half the participants (54%)
      perceived that they had oral problems: esthetic issues predominated (33%), but
      pain (17%), cavities (15%) and difficulty chewing (8%) were also reported. Most
      participants (94%) had dentitions of > or = 20 teeth. There was a weak but
      significant negative correlation between age and number of teeth (r2=0.03,
      p<0.001). Age and female gender were significantly associated with pain, bleeding
      gums and periodontitis. Pain was a more frequent complaint among poorly educated
      subjects than among the better educated. Diabetics comprised 17% of respondents
      and reported higher frequencies of dental problems, bleeding gums and calculus
      and fewer teeth. However, after compensation for age, gender, smoking, education
      and income, no significant associations were disclosed. Smoking was reported by
      30% of all subjects and was significantly associated with pain, bleeding gums and
      periodontitis. CONCLUSION: The survey disclosed that over half the subjects in
      this sample of underprivileged Pakistani adults suffered from poor oral health,
      including pain.

PMID- 16813137
TI  - Clinical application of a VSCs monitor for oral malodour assessment.
AB  - PURPOSE: The purpose of this study was to evaluate a volatile sulfur compounds
      (VSCs) monitor's ability to assess oral malodour in patients with and without
      periodontal disease in comparison with the assessment by gas chromatography (GC)
      or organoleptic testing. MATERIALS AND METHODS: Ninety-nine patients' mouth air
      was measured by GC, a VSCs monitor (Breathtron) and organoleptic test. Patients
      who had a periodontal pocket depth of 4 mm and more for at least two tooth
      surfaces were assigned to the periodontal disease group. RESULTS: Total VSCs
      value by the Breathtron was higher in periodontal disease group than that in non
      periodontal disease group, and it showed statistically significant correlations
      with specific VSCs gases from GC and with the organoleptic measurement. The
      Breathtron had high sensitivity in both groups. CONCLUSION: The Breathtron can be
      a reliable instrument for the diagnosis of halitosis. However, the Breathtron
      should be used properly for measuring VSCs that are related to periodontal
      disease.

PMID- 16813138
TI  - Efficacy of interdental plaque control aids in periodontal maintenance patients:
      A comparative study.
AB  - PURPOSE: To compare the interdental plaque removal capacity of dental floss, a
      cylindrical and a conical interdental brushes. MATERIAL AND METHODS: Fifty
      individuals were selected from those attending a maintenance programme for
      periodontally treated patients. Upon written agreement, the Silness and Loe
      Plaque Index (Pl.I) was registered in nine interdental spaces in three quadrants.
      The patients were then instructed on the use of each device and performed the
      cleaning until they felt it was satisfactory using one instrument for each
      quadrant. The same calibrated examiner registered Pl.I again, unaware of the
      instruments used in each quadrant. Mean values were calculated and compared by
      One Way ANOVA + Bonferroni and paired sample t test (alpha=.05). Frequency
      distribution of scores 0+1 and 2+3 was also calculated and compared by Mc Nemar.
      RESULTS: The mean Pl.I at start was 1.71 for dental floss, 1.69 for the conical
      and 1.66 for the cylindric interdental brushes. All three instruments reduced
      plaque significantly. Thus, the final mean Pl.I was 1.02, 0.46 and 0.42 for
      floss, conical and cylindric brushes, respectively. The final values observed for
      the interdental brushes were significantly smaller than those observed for floss.
      The same result was observed for the frequencies of 0+1 and 2+3 criteria of the
      Pl.I. CONCLUSION: It may be concluded that, for individuals in periodontal
      maintenance care, interdental toothbrushes, regardless of their shape (conical or
      cylindric) are more efficacious in interdental supragingival plaque removal than
      dental floss.

PMID- 16813139
TI  - Dental plaque removal efficacy of three toothbrushes with different designs: A
      comparative analysis.
AB  - PURPOSE: This study aimed to compare dental plaque removal efficacy of three
      manual toothbrushes. MATERIALS AND METHODS: Three toothbrushes (Colgate Flexivel 
      Colgate (T1), Oral B Advantage Control Grip - Oral B (T2), Comfort Clean -
      Johnson & Johnson - Reach (T3) were evaluated for dental plaque removal in 17
      subjects. Dental plaque was scored before and after seven days' use of each
      toothbrush, employing an adaptation of Quigley-Hein Index modified by Turesky
      (Plaque Index). Assessments were performed at days 0, 7, 14, 21, 28, and 35. At
      the end of the trial each subject was asked which toothbrush was preferred.
      RESULTS: Final dental plaque scores for toothbrush T3 were statistically
      different from toothbrushes T1 and T2, which in turn did not differ from each
      other. Subjects showed preference towards toothbrush T3. CONCLUSION: Toothbrush
      T3 was more efficient in terms of dental plaque removal when compared with
      toothbrushes T2 and T1.

PMID- 16813140
TI  - Alveolar bone loss and reported medical status among a sample of patients at a
      Saudi dental school.
AB  - PURPOSE: Periodontitis is a common chronic disease globally. It is a major cause
      of tooth loss among adults, and recently has been suggested as a possible risk
      factorfor some systemic diseases such as cardiovascular disease. In Saudi Arabia,
      research on periodontitis prevalence, as well as its relation to systemic
      diseases, is lacking. The objectives of this study were: (1) to determine the
      prevalence of periodontitis among a sample of Saudi Dental School patients
      population; and (2) to examine the association between periodontitis and systemic
      diseases in the selected sample. MATERIALS AND METHODS: Retrospective evaluations
      of 282 randomly selected dental records were conducted. Age, gender, nationality
      and medical history were abstracted from these records. Number of remaining teeth
      and number of teeth with more than 20% of bone loss were determined from
      panoramic radiographs. Descriptive statistics, t-test, chi-square and regression
      models were used for data analyses. RESULTS: About 68% of the sample had
      radiographic alveolar bone loss; of these, 28% had a localised and 40% had a
      generalised form. Prevalence of systemic diseases was generally higher among
      individuals with the generalised form. About 21% and 13% of those with
      generalised periodontitis reported history of diabetes and hypertension
      respectively, whereas only about 2% of those with localised periodontitis
      reported history of these diseases. CONCLUSION: The findings of the present study
      showed a high prevalence of periodontitis in the selected sample. There is an
      urgent need for further studies with larger sample size to confirm these findings
      and to implement an effective measure to reduce periodontitis prevalence in Saudi
      Arabia.

PMID- 16813141
TI  - Marginal bone level in an adult Danish Population.
AB  - PURPOSE: To investigate the prevalence and distribution of marginal bone loss in
      the Danish population. MATERIALS AND METHODS: Six hundred and sixteen randomly
      selected Danish adults (304 females and 312 males), mean age of 42 years (range
      21-63 years) underwent a full-mouth radiographic survey consisting of 14
      periapicals and two bitewings. The marginal bone level was measured with a
      digital caliper in mm, rounded off to the nearest 0.1 mm. The measurements were
      performed at the mesial and distal aspect of the tooth, from the cemento-enamel
      junction to the marginal bone. These measurements were used to calculate the
      marginal bone level (A) in mm for each tooth and each patient. Three thresholds
      were defined: normal marginal bone level (A < 3 mm), borderline marginal bone
      level (3 mm < or = A < 4 mm) and reduced marginal bone level (A > or = 4 mm).
      RESULTS: The prevalence of reduced marginal bone level in the individual and the
      frequency of teeth with reduced marginal bone level were almost similar. A
      reduced marginal bone level was evenly distributed among the tooth groups.
      Approximately 12% had reduced marginal bone level, 12% were in the borderline
      marginal bone level group, and the remaining 76% had a normal marginal bone
      level. The marginal bone level was ever more reduced with increasing age. No
      significant difference in bone level was observed between genders. CONCLUSIONS:
      The prevalence of reduced marginal bone level in a random Danish population is
      approximately 12% and is comparable to findings in other European countries.

PMID- 16813142
TI  - Demographic, socio-economic, behavioural and clinical variables associated with
      caries activity.
AB  - This study investigated the association between several demographic, socio
      economic, behavioural and clinical variables on caries activity. One hundred and
      two patients were randomly retrieved from the files of the Operative Dentistry
      Clinic (UFPel-Brazil). The patients gave written consent to participate in the
      study. They were interviewed reporting demographic (sex and age), socio-economic
      data (income, educaional level) and oral health behaviours (tooth-brushing
      frequency, dental floss usage and snacks frequency). Intraoral examination was
      performed to investigate the clinical variables (presence and quality of biofilm,
      DMFT and modified DMFT index and bleeding points). Patients were divided between
      caries-active (n=51) and caries-inactive (n=51), according to the presence of
      white spot lesions and/or active cavity lesions. Statistical analysis was carried
      tout using Chi-square or Fischer's exact test, with the confidence level at 95%.
      Results demonstrated that several conditions (younger subjects, lower educational
      or income levels, lower tooth-brushing frequency, higher snacks frequency,
      adherent biofilm, presence of bleeding points and higher modified DMFT index)
      were associated with caries activity in the studied population. Within the
      limitations of the experimental design, and considering the population under
      investigation, it was verified that demographic (age), socio-economic (income and
      educational levels), behavioural (tooth brushing and snacks frequencies) and
      clinical (modified DMFT index, presence and quality of biofilm, and bleeding
      points) variables were associated with caries-active patients.

PMID- 16813143
TI  - Obesity and dental caries--A systematic review.
AB  - PURPOSE: The purpose of this paper was to undertake a systematic review about the
      relationship between obesity in childhood, adolescence and/or adulthood and the
      prevalence of dental caries. METHODS: The authors searched Bireme, Medline, ISI,
      Cochrane Library and the internet for papers from 1984-2004. The main search
      terms were 'obesity' and 'dental caries'. The inclusion criteria were studies
      that defined obesity (body mass index) and dental caries (total number of
      decayed, and filled teeth - DFT/DFS/dft/dfs) in their subjects. The following
      were excluded from this paper: articles on reviews, dietary guidelines, policy
      statements, papers related to oral health and nutrition deficiency--underweight,
      and with no relation between obesity and dental caries prevalence or dental
      health problems. RESULTS: No systematic review has focused on correlating obesity
      and caries and only three stud ies had high levels of evidence. CONCLUSION: Only
      one study with high level of evidence showed direct association between obesity
      and dental caries. In view of the findings, further well-designed randomised
      studies are needed to demonstrate the relationship between dental caries and
      obesity.

PMID- 16813144
TI  - In vivo reliability of an infrared fluorescence method for quantification of
      carious lesions in orthodontic patients.
AB  - The aim of this study was to evaluate the reliability of a laser-induced infrared
      fluorescence method, DIAGNOdent, for measuring orthodontically induced white spot
      lesions. The subjects comprised 13 orthodontic patients, aged 13-17 years, who
      had recently completed fixed appliance therapy: 137 test teeth were selected,
      with white spot lesions on the facial or buccal smooth surfaces. An initial
      visual inspection was performed to localise and record the measuring region. The
      predetermined measuring regions were scanned to locate the sites of the highest
      reading. The readings and their corresponding sites were registered on the print
      out photographs. Following the measurement by the first examiner, the second and
      the third examiners took DIAGNOdent readings independently at the same lesion
      sites indicated on the photographs, under identical conditions. One week later,
      DIAGNOdent readings of the same lesions were retaken by the three observers
      working independently. Intra- and inter- examiner agreements on DIAGNOdent
      quantification of lesion severity were analysed by Intra-class correlation
      coefficient (ICC). The ICC values for intra-examiner agreement for the three
      examiners were 0.91, 0.97, and 0.98, respectively, with a mean value of 0.95,
      indicating excellent agreement. The ICC values for inter-examiner agreement were
      comparatively lower: 0.69 and 0.82 for the first and second measurements,
      respectively. It was concluded that the reliability of the DIAGNOdent readings on
      white spot lesions associated with orthodontic banding was good.

PMID- 16813145
TI  - Population- vs. risk-based applications of fissure sealants in first permanent
      molars: a 13-year follow-up.
AB  - PURPOSE: To evaluate and compare the long-term outcome of a population-based and
      a risk-based strategy of applying fissure sealants in newly erupted first
      permanent molars. DESIGN AND SETTING: Retrospective cohort study in primary
      dental care. MATERIALS AND METHODS: Four hundred and ninety-six subjects from two
      cohorts were included. In group P (n = 236), routine applications of fissure
      sealants were conducted while sealants were placed on the basis of subjective
      criteria in Group R (n = 260). Data of applications, maintenance, decay,
      restorations, extractions, and cumulative time of applications from six to 19
      years were extracted from the dental records and bite-wing radiographs by two of
      the authors simultaneously. The main outcome measures were the total caries
      prevalence at the age of 19 years as well as the fate of each sealed and non
      sealed occlusal surface. RESULTS: In group P, 87.7% of all first permanent molars
      were sealed compared with 20.2% in group R. There was no statistically
      significant difference concerningthe total DFT at 19 years of age between the
      groups (mean 3.5 +/- 3.8 vs. 3.7 +/- 3.4). Considering the occlusal surfaces of
      the first permanent molars only, a statistically significant treatment effect was
      demonstrated in group P with an odds ratio of 4.6 (95% CI: 3.0 - 6.7; p < 0.05).
      The absolute risk reduction was 36.3% and the number needed to treat was 2.8. In
      Group R, no statistically significant treatment effect was disclosed (OR = 1.3;
      95% CI: 0.9 - 1.7; risk reduction 5.5%). CONCLUSION: This 13-year follow-up
      showed that population-based applications of fissure sealants in first permanent
      molars shortly after eruption showed a statistically significant treatment effect
      on the occlusal surfaces at the age of 19 years, which was in contrast to
      findings from a cohort in which sealants were applied on the basis of an
      individual risk-based strategy. There were, however, no significant differences
      concerning the total caries experience between the two cohorts.

PMID- 16813146
TI  - [New ideas of the physiological role of the genes' HLA in reproductive process].
AB  - The data presented in this paper shows the role of HLA genes and their products
      HLA-antigens in reproduction. The study is concentrated on new ideas of the role
      and mechanisms underlyin the functions of both classical and newly determined HLA
      genes and their products: New data and hypotheses on HLA-molecules' role in
      "physiological" pregnancy are discussed.

PMID- 16813147
TI  - [Novel mechanisms of neuronal synapse-specific plasticity].
AB  - According to modern view, structural and functional changes in definite synaptic
      connections underlie the long-term memory (synapse-specific plasticity). These
      changes are translation- and transcription-dependent. The results obtained with
      mollusk neurons or mammalian hippocampus showed that molecular and genetic
      regulation is not needed for each single synapse. It was found that stimulation
      of synapse initiated activation of second messengers in it as well as "synaptic
      tagging" (specific marking of activated synapses) and formation of mechanisms for
      local "catching" of transcripts. Second messengers induced the RNA and protein
      molecule synthesis in neuron soma which spreads to all neuritis but selectively
      incorporate only at tagged synapses activated by the stimulation, resulting in
      long-term changes in functional and morphologic characteristics (parameters) of
      these synapses. Results of our experiments suggest that, during sensitization,
      different second messenger systems (and genes which it regulates) are involved in
      plasticity of definite synaptic inputs. It was found that cAMP and cAMP-dependent
      transcription factors C/EBP (CAAT/enhancer binding protein) induced long-term
      changes in sensory inputs from chemoreceptors of the head part of snail in L-RP11
      neurons, while proteinkinase C and proteinkinase C-dependent transcription factor
      SRF are involved in long-term regulation of synaptic inputs from mechanoreceptors
      of the head part of snail in the neurons. The immediate early gene zif268
      regulates synaptic inputs from both chemo- and mechanoreceptors of the snail
      head. Our experimental data support the hypothesis of selective neurochemical
      "projection" of synaptic connections onto certain genes of neuron.

PMID- 16813148
TI  - [Restoration of microcirculation in the brain during ischemia].
AB  - The work shows that, after slinging two carotids in rats, the blood pressure in
      the circle of Willis decreases to approximately 40 mm Hg. The developing ischemia
      is accompanied by a mass adhesion of leukocytes to the walls of the brain venules
      and smallest veins. In two hours after slinging, the blood pressure in the
      vessels of the circle of Willis decreases to 16-20 mm Hg. The rate of adhesion
      increases abruptly. In these vessels the leukocyte conglomerates are formed which
      results in complete occlusion of the vessels and the death of animals. These
      processes are shown to be reversible. The insertion of 4.0-4.5 ml of
      plasmosubstituent polyglucin into the vessels of the circle of Willis "washes
      away" the leukocyte conglomerates as well as a part of adhered leukocytes and
      restores the blood flow in the venules and smallest veins for 10-15 min.

PMID- 16813149
TI  - [Paticipation of cannabinoid receptors in the regulation of cardiac rhythm and
      cardiac contractility].
AB  - It has been found that i. v. administration of cannabinoid receptor (CB) agonists
      (HU-210, ACPA, anandamide, methanandamide) induced a decrease in the heart rate
      (HR) in anesthetized rats. Pretreatment with CB1 receptor antagonist SR141716A
      completely abolished a negative chronotropic effect of CB receptor agonist HU
      210. The CB2 receptor antagonist SRI 44528 did not prevent a HU-210-induced
      decrease in the HR. Pretreatment with the ganglion blocker hexamethonium had no
      effect on the negative chronotropic action of HU-210. Addition of HU-210 (100 nM)
      to perfusion solution induced a decrease in the HR, left ventricular development
      pressure, rate of contractility and relaxation of isolated perfused rate heart
      without change in end diastolic pressure. These data suggest that cardiac CBI
      receptor activation induces a decrease in the HR both in vivo and in vitro. An
      occupancy of the same receptors mediates a negative inotropic effects of
      cannabinoids.

PMID- 16813150
TI  - [Comparative analysis of conditioned passive avoidance retention in rats with
      different forms of inherited arterial hypertension].
AB  - Comparing behavioral traits of anxiety in elevated plus-maze and retention of
      passive avoidance response in two rat strains with hereditary arterial
      hypertension ISIAH (inherited stress induced arterial hypertension) and SHR
      (spontaneously hypertensive rats) has shown the following. The SHR rats
      demonstrate impairment in retrieval of passive avoidance, hyperactivity and low
      anxiety. ISIAH rats showned better avoidance performance, average level of
      anxiety and activity. The interdependence of two pathologies: hypertension and
      memory impairment is discussed.

PMID- 16813151
TI  - [Influence of intracerebroventricular infusion of beta-amyloid peptide on
      learning dynamics in Wistar and non-linear rats].
AB  - Effect of intracerebroventricular infusion of beta-amyloid peptide fragment
      Abeta(25-35) on light-dark discrimination in a Y-maze with positive food
      reinforcement, assessed as a decrease in the number of errors, was investigated
      in Wistar rats and non-linear rats. We proposed to use exponential mathematical
      model for the learning curve that represents the transfer function for the first
      order system together with regression analysis. Dynamics of learning in Wistar
      and non-linear rats coincided with the model. Injection ofbeta-amyloid into the
      right lateral ventricle of the brain led to a disruption in performance between
      the first and the second session without total cessation of the learning process.
      This disappearance of the curve may be the first sign of the initial effect of
      beta-amyloid because Student's t-test did not reveal any significant difference
      between control and amyloid-treated Wistar rats. Beta-amyloid in non-linear rats
      only decreased the velocity of learning though kept being similar to the
      mathematical model. These results suggest that the non-linear rats possess some
      genetically specified defense mechanism against damaging action of beta-amyloid.

PMID- 16813152
TI  - [Phenazine methosulfate system-induced membrane hyperpolarization in the human
      erythrocytes].
AB  - Erythrocyte membrane potential was recorded via measurement of pH of the
      incubation medium in presence ofprothonophore. The increase of intracellular
      calcium concentration in presence of calcium ionophore A23187 and addition of the
      artificial redox-system ascorbate-phenazine methosulfate led to membrane
      hyperpolarization due to opening of Ca(2+)-activated potassium channels that are
      regulated by multiple signaling pathways. The opening of the Ca(2+)-activated
      potassium channels in presence of artificial redox-system ascorbate-phenazine
      methosulfate is mediated at least by two mechanisms including an increase in
      affinity of channels to calcium ions and involvement of the protein SH-groups and
      the components of the respiratory circuit which have beer found in erythrocyte
      membrane.

PMID- 16813153
TI  - [The role of physiology in modern surgery].
AB  - Through the analysis of recent achievements in the field of surgery we have
      demonstrated convincingly that physiological studies in both humans and animal
      models are the keystone of modern surgery. Physiological studies of blood
      circulation, respiration, digestion and other functions have laid the foundations
      for major fields of surgery. Their role is the most evident in the development of
      cardiac surgery. Notably, one of the outstanding breakthroughs in the medical
      science of the 20th century--the extracorporeal blood circulation--was made by
      the Russian physiologist S. S. Bryukhovenko. We have shown that noninvasive
      diagnostic procedures such as echocardiography are of outmost significance on all
      stages of the surgical treatment (pre- and intraoperational diagnostics and
      medical rehabilitation). The great impact of physiology on the development of
      surgery has also led to the progress of related fields of medicine-
      anesthesiology, intensive care, functional diagnostics, transplantation,
      rehabilitation, and many others.

PMID- 16813154
TI  - [Hormonal function of the hypophyseal-adrenocortical system in the pathogenetic
      heterogeneity of post-stress depressions].
AB  - Original behavioral strategy is an important prerequisite for the pathogenesis of
      post-stress psychopathologies. Heterogeneity of these pathologies depends on the
      functional activity of hypophyseal-adrenocortical system.

PMID- 16813155
TI  - [Psychotropic effects of diazepam in male mice with alternative psycho-emotional
      statuses].
AB  - Effects of diazepam (0.1, 0.5 and 1 microg/kg, i. p.) on communicative, anxious
      behaviors, exploratory activities and sexual motivation of C57BL/6J male mice
      with alternative psychoemotional statuses (intact and anxious) were studied.
      Increased level on anxiety was formed by sensory contacts technique. Behavioral
      effects of diazepam depend on initial psycho-emotional status of animals. The
      compound has an anxiolytic effect in new situation on anxious males but does not
      have it in situation of social contacts. Diazepam reinforces initial sexual
      interest in anxious mice; however, it does not enable correct exhaustion of
      sexual motivation. Furthermore, the compound provokes development of the
      exhaustion in intact male mice.

PMID- 16813157
TI  - [Dynamics of renal medullary vinculin under changing of osmoregulating function].
AB  - Reduction of vinculin occurs in the renal medulla under the long-lasting
      dehydration. The protein content measured in inner medulla of rats of the WAG
      line under hydration was 92.1 +/- 6.3 in relative units, but it was only 77.6 +/-
      2.3 after a 3-day water deprivation. The vinculin content in the inner medullar
      layer from mutant rats of Brattleboro line incapable of synthesizing vasopressin
      is essentially higher: it is 188.9 +/- 8.5 in hydrated conditions and drops to
      148.4 +/- 7.3 under a 3-day dehydration. The same high level of vinculin is in
      outer medulla from rats of Brattleboro line: 222.1 +/- 11.8 in hydrated animals
      and 174.9 +/- 11 after a 3-day dehydration. No differences were revealed in
      response of vinculin to alternative osmoregulating stimulation in cortex in both
      rat lines.

PMID- 16813158
TI  - [The school: modern course of lectures on classical physiology].

PMID- 16813156
TI  - [Some neuroendocrinological changes in rats of cataleptic strain GC. Influences
      of ontogenesis and generation of breeding].
AB  - The content of biogenic amines: dopamine, noradrenaline and serotonine, in rats
      of cataleptic strain GC as compared with the control strain Wistar at the age of
      1 and 5 months is decreased, the maximal decrease being found in the so-called
      "nervous" animals. The aldosterone content was decreased at 5 month age in the GC
      rats. The testosterone content at the age of 1 month in GC rats does not differ
      from that in Wistar rats, but at the age of 5 months it was decreased as compared
      to Wistar, the maximal decrease being found again in "nervous" GC rats. The data
      obtained point to peculiarities of ontogenetic regulation and to commonness of
      mechanisms of catalepsy and "nervousness" in GC rats.

PMID- 16813159
TI  - [RNA interference: biology and perspectives of application in biomedicine and
      biotechnology].
AB  - RNA interference (RNAi) is among the most particular mechanisms of gene
      expression regulation. Besides, small interfering RNAs are significant players in
      cell defence either from viral infection or retrotransposons. Medical utilization
      of RNAi gives a handful of ways to cure viral and oncological illnesses. RNA
      interference, also, represents a useful tool for research, because it allows
      quick production of monogene functional knockouts. In this review we describe the
      most recent conceptions about RNAi mechanisms and actual approaches for it's
      usage.

PMID- 16813160
TI  - [Calcium-regulated photoproteins of marine coelenterates].
AB  - Ca(2+)-regulated photoproteins are bioluminescent proteins responsible for
      bioluminescence of marine coelenterates. The photoprotein molecule is a stable
      enzyme-substrate complex consisting of a single polypeptide chain and an oxygen
      "pre-activated" substrate, 2-hydroperoxycoelenterazine, which is tightly but non
      covalently bound with a protein. The bioluminescence is triggered by calcium ions
      and originates from an oxidative decarboxylation of a protein bound substrate.
      The review provides current data on the photoproteins structure, the mechanism of
      bioluminescent reaction, the function of some amino acid residues of an active
      site in the catalysis and the formation of the emitter, as well as on
      applications of these proteins in a bioluminescent analysis.

PMID- 16813161
TI  - [Cloning, sequence analysis and heterologous expression of a beta-mannanase gene
      from Bacillus subtilis Z-2].
AB  - Mannanase, an extracellular enzyme catalyzes the hydrolysis of hemicelluloses to
      produce oligosaccharides, has a potential to be applied in food industries. In
      this study, a mannanase gene from B. subtilis Z-2 was isolated through PCR
      screening of a genomic DNA library. The nucleotide sequence of the mannanase
      gene, man, contained an open reading frame of 1.080 bp, which codes for a deduced
      26 amino-acid signal peptide and a mature protein with the deduced molecular mass
      of 38 KDa. The man gene can both be expressed heterologously into the periplasm
      in plasmid pET22b(+) containing intact signal peptide (pET-NdeI18) and the pelB
      signal peptide of the pET22b(+)vector (pET-NcoI3). The Escherichia coli BL21
      (DE3) containing pET-NcoI3 secreted about twice as much mannanase as that
      harboring pET-NdeI18. In E. coli DH5alpha, expression of man was under the
      control of the lac promoter in the pRK415 vector and was much more effective when
      the Shine-Dalgamo (SD) sequence was changed from GGGGAG to AAGGAG and the start
      codon was changed from TTG to ATG, respectively. These results suggest that
      genetic modification of the SD sequence and start codon is practical for high
      level expression of mannanase in different bacterial strains.

PMID- 16813162
TI  - [RET and GFRA1 germline polymorphisms in medullary thyroid cancer patients].
AB  - The role of RET and GFRA1 germline polymorphisms in predisposition to sporadic
      medullary thyroid cancer (MTC) and polymorphisms' modulation effect on clinical
      features of inherited and sporadic MTC were investigated. Blood samples from 67
      MTC patients (22 hereditary and 45 sporadic), 3 asymptomatic mutant RET gene
      carriers and 178 ethnically matched healthy control individuals were tested.
      Screening of RET exons and portion of introns 1, 8, 10, 13, 14, 15, 16 and GFRA1
      5'-UTR was performed by means of direct sequencing and PCR-RFLP. 8 polymorphic
      variants of RET gene (exons 11, 13, 14, 15 and introns 1, 8, 13, 14) and 4 GFRA1
      polymorphisms in GFRA1 were detected. Linkage disequilibrium was found between
      RET variants G691S and S904S, L769L and IVS8, S836S and IVS13. In sporadic MTCs,
      allelic frequency of only one polymorphic RET variant, L769L, was significantly
      decreased versus control group. In hereditary MTCs, a significant over
      representation of S836S and under-representation of S904S sequence variants were
      observed as compared to sporadic MTCs and controls. No co-segregation was found
      between individual polymorphisms and phenotype of sporadic MTC. In patients with
      inherited MTC whose genotype was presented with polymorphic L769L and wild-type
      S836S, disease onset occurred 20 years later than in individuals with polymorphic
      L769L and S836S or wild-type L769L (p = 0.01) suggestive of a possible protective
      role of L769L in MTC development and modulating effect of a combination of L769L
      with wild-type S836S on clinical outcome of inherited MTC.

PMID- 16813163
TI  - [Loss of heterozygosity at chromosome 6 as a marker of early genetic alterations
      in cervical intraepithelial neoplasias and microinvasive carcinomas].
AB  - Oncogenic human papilloma viruses (mostly HPV types 16 and 18) are the major
      cause of cervical intraepithelial neoplasia (CIN) that progress into cervical
      cancer (CC). To reveal early genetic alterations at chromosome 6 important for CC
      progression we have analyzed loss of heterozygosity (LOH) in DNA from 45 CIN
      cases, 47 microcarcinomas and 19 invasive squamous cell carcinomas stage IB. LOH
      analysis of DNA samples prepared with microdissection from all CIN foci as well
      as from CC lesions and synchronous CIN has permitted the investigation of CIN and
      CC heterogeneity. 79% of CC stage 1 showed LOH with 6 microsatellite markers at
      chromosome 6. LOH with microsatellite markers D6S276 (6p22) and TNFalpha (6p21.3)
      was found in 50% of CC cases. LOH frequency in CIN lesions, synchronous with CC,
      was higher then LOH in CIN cases without cancer, the statistical significance (p
      = 0.004) was shown for marker D6S291 (6p21.2). The finding suggests that high
      level of LOH frequency in CIN lesions may be a marker of unfavorable prognosis
      for CIN. Progression from microcarcinoma to invasive CC of IB stage was
      associated with higher LOH frequency at D6S344 (6p25) and TNFalpha (6p21.3). The
      early genetic alterations were found in CIN with microsatellites D6S273 and
      TNFalpha located at 6p21.3. Moreover the LOH frequency at D6S273 retained the
      same in CIN and CC cases. Based on HPV-typing, LOH analysis and X-chromosome
      inactivation the polyclonality of CC lesions as well as CIN was shown in a few
      patients.

PMID- 16813164
TI  - [Genome-wide lentivector-based pooled shRNA library optimization].
AB  - We have optimized lentiviral vector constructs and cassettes for expression of
      short hairpin RNAs (shRNAs) in order to create genome-wide library capable of
      inhibition of full variety of human mRNAs. The vector optimization has resulted
      in 15-20-fold improvement in virus stock titers. We found that in the context of
      lentiviral vector the most effective structure for the shRNA is simple hairpin
      with 21 nucleotide stem. The shRNA-expressing lentiviral constructs contain
      choice of puro(R), copGFP or H-2K(k) selective markers. The efficiency of the
      optimized library was evaluated in experiments on screening of shRNAs that
      reactivate oncosuppressor p53 in HeLa cells. The cells contained reporter
      construct with p53-dependent expression of a fluorescent protein, which allows
      cytofluorimetric isolation of cell population with reactivated p53.

PMID- 16813165
TI  - [Binding of human ribosomal protein S5 with the 18S rRNA fragment 1203-1236/1521
      1698].
AB  - Human ribosomal protein S5 is a homologue of prokaryotic ribosomal protein S7
      that binds to the 16S rRNA region formed by helices H28-30 and H41-43 and
      contacts this site within the 30S ribosomal subunit. To date, one of the most
      available approaches to study the structure of the eukaryotic ribosome is based
      on studying binding of rRNA transcripts with recombinant ribosomal proteins. In
      the present work, we report studying interaction of human recombinant protein S5
      with an RNA transcript "corresponding to the region 1203-1236/1521-1698 (helices
      H28-30 and H41-43) of human 18S rRNA. The homologous region of 16S rRNA is known
      to bind protein S7. The apparent association constant of S5 with the transcript
      was determined. Nucleotide residues of the transcript changing their
      accessibility for cleavage with RNases T1 and T2 in the presence of S5 were
      determined by the enzymatic footprinting. It was shown that these nucleotides are
      located preferentially in the internal loop of the fragment formed by basal parts
      of the helices H29, H30 and H41 that agrees with the data on the S7 binding to
      16S rRNA and on its location within the 30S ribosomal subunit. Besides, we also
      found nucleotides in the transcript regions corresponding to 16S rRNA regions
      that do not contact S7 in the 30S subunit.

PMID- 16813167
TI  - [Interdomain interactions in aspartic proteases of higher organisms and their
      analogs in retroviral enzymes].
AB  - A continuous chain of hydrogen bonded groups, which forms cross-hands interaction
      between domains in molecules of pepsin-like enzymes, has been revealed. The chain
      contains a pair of 6 symmetrically related hydrogen bonds between main chain
      atoms and the two conserved water molecules. The peptide groups forming hydrogen
      bond with the inner oxygens of the active carboxyls are important elements of the
      chain. The so-called "fireman grip" hydrogen bonding, consisting of a pair of the
      two symmetrically related bonds, is an integral part of this system of
      interactions. One of the water molecules in this system has a zero accessibility
      and forms a very short hydrogen bond with the active site interacting peptide
      group. This chain connects tightly the two regions of domains which have a high
      correlation in conformational mobility. The retroviral enzymes have an abortive
      chain of the interdomain interaction in this region which is reduced to the
      "fireman grip" net.

PMID- 16813166
TI  - [The conformational dynamic of the tetramer hemoglobin molecule as revealed by
      hydrogen exchange. II. Influence of the intersubunit contact splitting].
AB  - The rate of the H-D exchange of the peptide NH atoms of the isolated alpha and
      beta subunits of human Hb were studied at the pH range 5.5-9.0 and 20 degrees C
      by the IR spectroscopy. The factor retardation of the exchange rate of subunits 
      P in the range -10(2)-10(7). In comparison with tetramer Hb the probability of
      local fluctuations (1/P) is increased to a slightly greater extent for the
      monomeric alpha subunits then for the tetramer beta subunits. Unlike Hb
      oxygenation of subunits does not influence on the probability of the local
      fluctuations and subunits have no the pH-dependent change of the value 1/P
      observable for the ligand Hb. The possible mechanisms of the overall
      intensification of the local fluctuations upon the splitting of the Hb tetrameric
      contacts between subunits are discussed with the inviting of the structural
      crystallographic data.

PMID- 16813168
TI  - [Complexes of telomeric oligonucleotide d(TTAGGG)4 with the new recombinant
      protein PGEk--nucleic acid carrier into proliferating cells].
AB  - The complexation of the new protein vector PGEk--a carrier of nucleic acids into
      proliferating cells with phosphodiester d(TTAGGG)4 (TMO) and phosphorothioate
      Sd(TTAGGG)4 (TMS) telomerase inhibitor oligonucleotides was studied. PGEk
      molecule, consisting of 64 amino acids, is comprising the sequence of the human
      epidermal growth factor EGFh which is hydrophobic cell targeting moiety serving
      for receptor-mediated endocytosis and an NLS (nuclear localization signal) which
      is hydrophilic serving as a DNA-binding and selective nuclear import moiety.
      Experiments were carried out in 0.01 M Na-phosphate buffer contained 0.1 M NaCl,
      pH 7.8 at 37 degrees C. CD spectral analysis revealed that TMO molecules folded
      back into intramolecular antiparallel G-quadruplex while TMS molecules were
      represented as unstructured thread. The number of adsorbed PGEk molecules were
      estimated using PGEk intrinsic fluorescence decrease and fluorescence
      polarization increase of PGEk under oligonucleotide titration. Adsorption
      isotherms were plotted in Scatchard coordinates. We have shown that adsorption of
      the first two PGEk molecules on TMO and TMS occurs noncooperatively with the high
      association constants K1(TMO) = (7 +/- 1) x 10(7) M(-1) and K1(TMS) = (3 +/- 0.5)
      x 10(7) M(-1), respectively. Further adsorption up to 5-6 PGEk molecules on TMO
      occurrs cooperatively with still high association constant K2(TMO) = (4.0 +/-
      1.5) x 10(6) M(-1). TMS oligonucleotide binds the third PGEk molecule rather
      weakly, K2(TMS) = (8 +/- 2) x 10(5) M(-1). CD spectral analysis revealed that G
      quadruplex structure formed by TMO have undergone a partial unfolding by binding
      of PGEk molecules while single-stranded structure formed by TMS was not affected
      by binding PGEk. Thus, the tertiary structure of DNA and the number of adsorbed
      PGEk molecules formed biologically active compounds PGEk: TMO and PGEk: TMS were
      defined, which are able to penetrate through the membrane of proliferating cells
      and to suppress their growth.

PMID- 16813169
TI  - [Model of genes expression regulation in bacteria by means of formation of
      secondary RNA structures].
AB  - In this article a model, first, classical attenuation RNA regulation of gene
      expression by means of transcription termination is offered. The model bases on
      representation about a macrostate of secondary structure in RNA regulatory region
      between a ribosome and a RNA polymerase, on the formulas of a resonant type
      defining the value of deceleration of a RNA polymerase by a set of hairpins in
      the same region. The special attention is given to selection of parameters of
      model. To check of model the computer simulation is carried out and the
      dependences of transcription termination probability from the value of
      concentration charged tRNA are obtained, in particular, and from concentration of
      amino acid for many regulatory regions in genomes of bacteria (here data are
      presented for trpE genes in Streptomyces spp., Bradyrhizobium japonicum and
      Escherichia coli) and at various values of three parameters, which authors
      consider as the main. The obtained dependences are compounded with the accessible
      experimental data; including, under the form of the graphs concerning to activity
      of an enzyme depending on concentration of amino acid (for example, anthranilate
      synthase from tryptophan in S. venezuela). One possible usage: now attenuation is
      predicted usually by means of multiple alignment, it needs some sequences; the
      obtaining with the help of model on an individual sequence characteristic for
      attenuation or its absence of a curve at approaching parameters could be
      considered as argument for the benefit of presence or absence of attenuation.

PMID- 16813170
TI  - [Recognition of the potential SF-1 binding sites by SiteGA method, their
      experimental verification and search for new SF-1 target genes].
AB  - The SF-1 (Steroidogenic Factor-1) is a transcription factor known as a key
      regulator of the steroidogenic gene expression. SF-1 is required for the
      development and functioning at all levels of the hypothalamic-pituitary-gonadal
      and adrenal axis. Also it plays an essential role in sex determination. SF-1 is a
      member of the nuclear receptor superfamily and it activates gene expression by
      binding to DNA in a monomeric form. Here, we report the results of potential SF-1
      binding sites identification by using the SiteGA recognition method. The SiteGA
      method was implemented using a genetic algorithm (GA) involving a iterative
      discriminant analyses of local dinucleotide context characteristics. These
      characteristics were compiled not only over the core binding sites region but
      over its flanks as well. Developed SiteGA method is characterized by considerably
      better recognition accuracy when compared to that for the weight matrix method.
      The experimental tests demonstrated that 83% of the sites recognized by the
      SiteGA method in the regulatory regions of steroidogenic genes, indeed, interact
      with the SF-1 factor. We also estimated the density of predicted sites in
      regulatory region of genes, the members of different functional groups and
      developed the criterion to search for new SF-1 target genes in genome sequences.

PMID- 16813171
TI  - [ClusterTree-RS: the binary tree algorithm for identification of co-regulated
      genes by clustering regulatory signals].
AB  - Identification of groups of co-regulated genes (regulons) is an important part of
      studying transcriptional regulation. One possible approach is to cluster
      regulatory sites that were found using experimental or computational techniques,
      such as phylogenetic footprinting. This strategy doesn't require a priori
      knowledge about co-regulation and allows finding putative new members of known
      groups of co-regulated genes (i.e. a new regulon). Also, it allows finding new
      putative regulons, which is especially important for poorly annotated genomes. We
      have developed ClusterTree-RS, an algorithm for clustering regulatory signals
      using binary trees; it is presented in this paper along with some testing results
      on simulated and real data. The algorithm is implemented in Java and took about 2
      hours 40 minutes to cluster 1500 input signals on a computer with AMD Athlon 1.91
      GHz CPU.

PMID- 16813172
TI  - [Information about the protein secondary structure improves quality of an
      alignment of protein sequences].
AB  - All popular algorithms of pair-wise alignment of protein primary structures (e.g.
      Smith-Waterman (SW), FASTA, BLAST, et al.) utilize only amino acid sequences. The
      SW-algorithm is the most accurate among them, i.e. it produces alignments that
      are most similar to the alignments obtained by superposition of protein 3D
      structures. But even the SW-algorithm is unable to restore the 3D-based alignment
      if similarity of amino acid sequences (%id) is below 30%. We have proposed a
      novel alignment method that explicitly takes into account the secondary structure
      of the compared proteins. We have shown that it creates significantly more
      accurate alignments compared to SW-algorithm. In particular, for sequences with
      %id < 30% the average accuracy of the new method is 58% compared to 35% for SW
      algorithm (the accuracy of an algorithmic sequence alignment is the part of
      restored position of a "golden standard" alignment obtained by superposition of
      corresponding 3D-structures). The accuracy of the proposed method is
      approximately identical both for experimental, and for theoretically predicted
      secondary structures. Thus the method can be applied for alignment of protein
      sequences even if protein 3D-structure is unknown. The program is available at
      ftp://194.149.64.196/STRUSWER/.

PMID- 16813173
TI  - [Membrane probability profile construction based on amino acids sequences
      multiple alignment].
AB  - Prediction of membrane segments in sequences of membrane proteins is well known
      and important problem. Accuracy of the solution of this problem by methods that
      don't use homology search in additional data bank can be improved. There is a
      lack of testing data in this area because of small amount of real structures of
      membrane proteins. In this work, we create a testing set of structural alignments
      of membrane proteins, in which positioning of the membrane segments reflects
      agreement of known 3D-structures of proteins in the alignment. We propose a
      method for predicting position of membrane segments in multiple alignment based
      on forward-backward algorithm from HMM theory. This method not only allows to
      predict positions of membrane segments but also forms probability membrane
      profile, which can be used in multiple alignment methods that take into account
      secondary structure information about sequences. Method is implemented in
      computer program available on the World-Wide Web site
      http://bioinf.fbb.msu.ru/fwdbck/. Proposed method provides results better than
      MEMSAT method, which is nearly only tool for prediction of membrane segments in
      multiple alignments without additional homology search.

PMID- 16813174
TI  - [Molecular evolution of AdoMet synthetase by DNA recombination with a novel
      separate-mixing method].
AB  - We describe a new approach to in vitro DNA recombination termed Separate-Mixing
      method in this study. The reaction process of this method consists of two stages:
      at the first stage the reaction was implemented in two parallel teams, which
      generated random recombination by template-switching of growing polynucleotides
      from primers in the presence of unidirectional single-stranded DNA fragments used
      as templates, and then both teams were mixed together for further extension and
      recombination of DNA sequences at the second stage. Because of the particular
      strategy, the reaction process was also accompanied by the other two processes of
      DNA shuffling and StEP simultaneously. Two AdoMet synthetase genes sam2 from
      Saccharomyces cerevisiae and metK from Escherichia coli, which have only 56%
      homology on the DNA level were used for recombination with Separate-Mixing
      method. DNA recombination was available after a single round of reaction. With
      sequencing of 10 randomly selected recombinants, no unshuffled parental clone was
      found, and also no unexpected insertion, deletion or rearrangement was detected.
      An evolved gene sam' was obtained after screen and selection, which could
      obviously increase the accumulation of AdoMet in S. cerevisiae.

PMID- 16813175
TI  - [Polymorphism of aggrecan gene in families with idiopathic scoliosis].

PMID- 16813176
TI  - [Multi-central controlled study on three-part massage therapy for treatment of
      insomnia of deficiency of both the heart and spleen].
AB  - OBJECTIVE: To make multi-central clinical evaluation for three-part massage
      therapy for treatment of insomnia of deficiency of both the heart and spleen.
      METHODS: One hundred and sixty-six cases were randomly divided into a test group
      (n = 84) and a control group (n = 82). Multi-central, randomized and controlled
      methods were adopted. The test group were treated by the three-part massage
      therapy, i. e. acupoints at the head, abdomen and back were massaged, once each
      day; and the control group by oral administration of Guipi Pills [symbol: see
      text], 8 pills each time, thrice daily. The treatment was given for 15
      consecutive days and then the therapeutic effects were observed. RESULTS: Sixty
      seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in
      the test group, and the corresponding figures were 10, 21, 29 and 22 in the
      control group with a very significant difference between the two groups (P<
      0.001). The test group was superior to the control group in improvement for
      Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and
      Sleepless Depression Scale (SDS) (P < 0.001). CONCLUSION: The three-part massage
      therapy has definite therapeutic effect on insomnia of deficiency of both the
      heart and spleen with safety.

PMID- 16813177
TI  - [Clinical observation and study of mechanisms of needle-picking therapy for
      primary infertility of abnormal sperm].
AB  - OBJECTIVE: To search for the best method for increasing clinical therapeutic
      effect on primary abnormality of sperm. METHODS: One hundred and sixty-eight
      cases of infertility were randomly divided into a treatment group of 85 cases and
      a control group of 83 cases. The treatment group were treated with needle-picking
      at bilateral Shengzhi points, Dicong Shenjing points and L2 Shenjing points as
      main. The control group were treated with oral administration of Wuzi Yanzong
      Pills [symbol: see text]. Their therapeutic effects were observed in 3 hospitals.
      RESULTS: The total effective rate of 83.5% and the pregnancy rate of the
      patient's wife of 78.8% in the treatment group, and corresponding figures were
      54.2% and 43.4% in the control group, with a very significant difference between
      the two groups (P < 0.01); and reproductive hormones improved significantly after
      treatment in the two groups (P < 0.01); after treatment, superoxide dismulase
      (SOD) activity and Zn content in semen were elevated and cadmium level decreased
      significantly in the treatment group (P < 0.05). CONCLUSION: Needle picking
      therapy can significantly improve and regulate endocrine function, increase
      quality of semen and elevate pregnancy rate of the patient's wife for the patient
      of primary abnormal sperm.

PMID- 16813178
TI  - [Clinical observation on acupuncture for treatment of Tourette's syndrome].
AB  - OBJECTIVE: To explore an ideal program for acupuncture treatment of Tourette's
      syndrome (TS). METHODS: One hundred and two cases of TS were randomly divided
      into a treatment group of 68 cases and a control group of 34 cases. The treatment
      group were treated with acupuncture at Taichong (LR 3) and Hegu (LI 4) as main,
      and the control group with oral administration of heloperidol. Their therapeutic
      effects were compared, and changes of somatosensory evoked potentials (SEP)
      before and after treatment were investigated in the treatment group. RESULTS:
      After treatment for 3 courses, 56 cases were cured, 10 improved and 2 ineffective
      with an effective rate of 97.1% in the treatment group; and 15 cases were cured,
      11 improved and 8 ineffective with an effective rate of 76.5% in the control
      group, with a very significant difference in the effective rate between the two
      groups (P < 0.001); after treatment, the abnormal rate of SEP decreased by 41.1%
      in the treatment group (P < 0.001). CONCLUSION: Acupuncture is a very effective
      therapy for TS and has a certain restoring action on mild abnormal change of SEP.

PMID- 16813179
TI  - [Observation on clinical therapeutic effect of scalp acupuncture combined with
      body acupuncture on apoplectic hemiplegia].
AB  - OBJECTIVE: To search for the best method for increasing clinical therapeutic
      effect on apoplectic hemiplegia. METHODS: One hundred and twenty cases of
      apoplectic hemiplegia were randomly divided into three groups in order of
      visiting. Group A (n = 33) were treated by scalp acupuncture combined with
      consciousness-restoring resuscitation method, group B (n = 60) by scalp
      acupuncture combined with traditional acupuncture, and group C (n = 27) by
      traditional acupuncture. The clinical therapeutic effects were evaluated
      according to the scores of manner, speech, motor function of limbs, and so on.
      RESULTS: Three cases were basically cured, 20 were markedly effective, 7 were
      effective, with a total effective rate of 90.9% in the group A; and the
      corresponding figures were 7, 28, 21 cases and 93.3%, respectively in group B
      with no significant difference between the group A and B (P > 0.05); and 7 cases
      were markedly effective, 11 effective with a total effective rate of 66. 7% in
      the group C with a significant difference as compared with the group A and B (P <
      0.05, P < 0.001). CONCLUSION: Scalp acupuncture combined with consciousness
      restoring resuscitation method and scalp acupuncture combined with traditional
      acupuncture have a similar therapeutic effect on apoplectic hemiplegia, which is
      superior to that of traditional acupuncture.

PMID- 16813180
TI  - [Effects of acupuncture on blood-lipid levels in the patient of cerebral
      infarction with hyperlipidemia].
AB  - OBJECTIVE: To observe therapeutic effect of acupuncture method for consciousness
      restoring resuscitation on cerebral infarction with hyperlipidemia. METHODS:
      Sixty cases of apoplexy with hyperlipidemia were randomly divided into a
      consciousness-restoring resuscitation acupuncture group (treatment group) and a
      Chinese medicine control group (control group), 30 cases in each group. TCM
      symptomatic scores and indexes of blood lipids were detected before and after
      treatment in the two groups. RESULTS: The total effective rate for improvement of
      blood lipids was 72.4% in the treatment group, which was not different from that
      (65.5%) in the control group (P> 0.05); the total effective rate for clinical
      symptoms was 89.7% in the treatment group, which was better than that (62.1%) in
      the control group (P < 0.05). The treatment group was superior to the control
      group in improvement of numbness and twinge in extremities, dizziness, distention
      and oppressed feeling in chest and hypochondrium, anorexia, sleepy and weakness
      (P < 0.05). CONCLUSION: Acupuncture method for consciousness-restoring
      resuscitation can regulate metabolic disorder of lipids and improve main clinical
      symptoms in the patient of cerebral infarction with hyperlipidemia.

PMID- 16813181
TI  - [Clinical observation on acupuncture combined with microorganism pharmaceutical
      preparations for treatment of irritable bowel syndrome of constipation type].
AB  - OBJECTIVE: To explore the best program for treatment of irritable bowel syndrome
      (IBS) of constipation type. METHODS: Ninety-five cases of IBS were randomly
      divided into 3 groups. Group A (n = 30) were treated by acupuncture combined with
      microorganism pharmaceutical preparations, group B (n = 35) by oral
      administration of medicine for loosening the bowel to relieve constipation plus
      microorganism pharmaceutical preparations, and group C (n = 30) by simple
      acupuncture. RESULTS: The total effective rates were 90.0%, 77.2% and 66.7%, in
      the group A, B and C, respectively, with a very significant differences as the
      group A compared with those in the groups B, C (P < 0.01), and with no
      significant difference as the group B compared with that of the group C (P > 0.
      05). The intestinal available bacteria, bilidobacteria and lactobacillus,
      increased and enteric bacilli decreased in varying degrees in the 3 groups.
      CONCLUSION: Acupuncture combined with microorganism pharmaceutical preparations
      has a better therapeutic effect on irritable bowel syndrome of constipation type.

PMID- 16813182
TI  - [Four main schools of thought and analysis in studies of channels and
      collaterals].
AB  - OBJECTIVE: To summarize 4 schools of thought in studies of meridians. METHODS:
      Consult literature and review the history of studies of meridians. RESULTS: The
      studies of meridians in the past dozens years at home and abroad have gradually
      formed four main theories, namely the nerve-conduction meridian theory of
      neurophysiology, body fluid circulation meridian theory of the physio
      biochemistry, bio-field meridian theory of biophysics, and the connective tissue
      structure meridian theory of the overall-gap viewpoint, which are summarized and
      analyzed.

PMID- 16813183
TI  - [Anatomical study on Jingming (BL 1)].
AB  - OBJECTIVE: To explore the anatomical structures, and depth and direction of
      needling at Jingming (BL 1), so as to provide anatomical basis for its clinical
      application. METHODS: Forty-eight adult orbital specimens were observed by
      dissection. RESULTS: When a needle was vertically inserted into Jingming (BL 1),
      the needle tip will past through the skin, subcutaneous tissue, medial palpebral
      ligament, medialis rectus and orbital adipose body. Above the body of the needle,
      there are ophthalmic artery, anterior ethmoidal artery and nasociliary nerve. The
      average distance between the skin at the punctured point and the anterior
      ethmoidal artery is (18.25 +/- 4.45) mm, with an angle of (12.5 +/- 5.5) degrees,
      and the average distance between the skin at the punctured point and the optic
      nerve tunnel frontal point is (43.37 +/- 7.84) mm. CONCLUSION: To avoid bleeding
      caused by injuring the anterior ethmoidal artery, acupuncture at Jingming (BL 1)
      should avoid deeply inserting needled back-upwards and upwards, and the needling
      depth should not exceed 30.36 mm to avoid injury of the optic nerve tunnel
      frontal point.

PMID- 16813184
TI  - [Control study of therapeutic effects of three phase acupuncture method and
      routine acupuncture method on periarthritis of shoulder].
AB  - OBJECTIVE: To compare therapeutic effects of the three phase acupuncture method
      and routine acupuncture method on periarthritis of shoulder. METHODS: Randomized,
      controlled and single blind method was adopted and 70 cases were divided into a
      three phase acupuncture group and a routine acupuncture group, 35 cases in each
      group. Same acupoints were selected in the two groups and selection of acupoints,
      manipulation of the needle and motion in the three phase acupuncture group were
      conducted by stages. RESULTS: The effective rate was 97.15% in the three phase
      acupuncture group which was better than 87.10% in the routine acupuncture group
      (P < 0.05). After treatment, VAS scores decreased significantly in the two groups
      (P < 0.01), and there was a significant difference between the two groups in the
      difference of VAS after treatment (P < 0.01). CONCLUSION: The three phase
      acupuncture treatment was superior to the routine acupuncture therapy in
      therapeutic effect on periarthritis of shoulder.

PMID- 16813185
TI  - [Survey of development and present state of acupuncture and moxibustion
      literature abroad].
AB  - Statistics and analysis of the literature about academic studies of acupuncture
      and moxibustion 2006 ago are made by means of the authoritative medical
      literature data retrieving system MEDLINE, and the arrangement are made in order
      of the kinds of journals and the number of academic paper issued, so as to
      understand the survey of literature of acupuncture and moxibustion in the world
      and position of the literature of acupuncture and moxibustion of our country in
      the world.

PMID- 16813186
TI  - [Effect of electro-scalp acupuncture on cerebral dopamine transporter in the
      striatum area of the patient of Parkinson's disease by means of single photon
      emission computer tomography].
AB  - OBJECTIVE: To probe the mechanism of electro-scalp acupuncture in treatment of
      Parkinson's disease (PD) by single photon emission computer tomography (SPECT).
      METHODS: Five cases of PD received electro-scalp acupuncture at Dingnie
      Qianxiexian (MS 6), Epangxian III (MS 4), Dingpangxian I (MS 8), Dingpangxian II
      (MS 9) and Zhenxia Pangxian (MS 14). Contralateral points were selected for
      pathologic change on one side and bilateral points were selected for pathologic
      lesion on both sides. All the patients received 99mTc-TRODAT-1 SPECT examination
      before and after acupuncture treatment of 6 weeks. And activities of dopamine
      transporter (DAT) were analyzed by the ratio of striatum/occipital lobe (ST/OC),
      which was evaluated by means of technique of regional of interesting (ROI).
      RESULTS: The ratio of ST/OC on the same side of the affected extremity before and
      after treatment were 1.19 +/- 0.15 and 1.24 +/- 0.31 respectively. And on the
      other side were 0.90 +/- 0.12 and 0.95 +/- 0.25 respectively. They were increased
      after treatment (P > 0.05). CONCLUSION: Electro-scalp acupuncture can decrease
      the loss of DAT and improve the activities of DAT in the striatum of the patient
      of PD.

PMID- 16813187
TI  - [Anti-arrhythmic effect of acupuncture pretreatment in the rat of myocardial
      ischemia the post-receptor signaling pathway of beta-adrenergic receptor].
AB  - OBJECTIVE: To observe anti-arrhythmic effect of acupuncture pretreatment in the
      rat of myocardial ischemia and reperfusion (MIR) and to explore the role of cAMP
      and Gsa protein in beta-adrenergic receptor signaling. METHODS: MIR was produced
      by ligation and reperfusion of the left anterior descending coronary artery in
      the rat. Arrhythmic score, content of cAMP and Gsalpha protein in ischemic
      myocardium were compared among the normal control (NC), ischemia and reperfusion
      (IR), electroacupuncture (EA) and EA plus propranolol (EAP) groups. RESULTS: The
      arrhythmic score in the IR group at 10 min after reperfusion was higher than the
      NC group (P < 0.01); in the EA group the score was decreased (P < 0.01 vs the IR
      group); the score in the EAP group was similar to the IR group, much higher than
      the EA group (P < 0.01). The similar results for the contents of cAMP and Gsalpha
      protein were found in the ischemic myocardium. It is suggested that EA
      pretreatment significantly attenuates the arrhythmic incidence rate and the
      enhancement of the contents of myocardial cAMP and Gsalpha protein induced by
      MIR, and the attenuating effect is significantly inhibited by the intraperitoneal
      pretreatment of propranolol, a specific beta-adrenoceptor antagonist. CONCLUSION:
      Pretreatment of EA can produce anti-arrhythmic effect in the rat of MIR, which is
      mediated by the post-receptor signaling pathway of beta-adrenergic receptor.

PMID- 16813188
TI  - [Effects of electroacupuncture on GDNF positive cell immunoreactivity in local
      dermal tissue of the inflammatory pain focus in the rat of adjuvant arthritis].
AB  - OBJECTIVE: To study on the analgesic mechanism of electroacupuncture (EA) in the
      rat of adjuvant arthritis (AA). METHODS: Forty-eight SD rats were randomly
      divided into a blank control group (n = 8), an inflammatory group (n = 10), an
      acupoint EA group (n = 10), a non-acupoint EA group (n = 10) and a contralateral
      acupoint EA group (n = 10). Complete Freund's adjuvant (CFA) 50 microL were
      injected into the left malleolus' articular cavity in the rats except the blank
      control group for preparing single local adjuvant arthritis (AA) model. EA was
      given every other day to the acupoint EA group, the non-acupoint EA group and the
      contralateral acupoint EA group. The improving effects of EA at "Huantiao" (GB
      30) and "Yanglingquan" (GB 34) on the dorsal flexion pain score and the swell of
      dorsum of hind paw were investigated, and effects of EA on Glial cell line
      derived neurotrophic factor (GDNF) positive cells immunoreactivity in the
      inflammatory tissue of the AA rats on the 14th day after injection of adjuvant
      were observed with immunohistochemical technique. RESULTS: Hyperalgesia and local
      swell, and GDNF in the dermal and subcutaneous tissue around the inflammatory
      ankle joint in the inflammatory groups were significantly higher than those in
      the blank control group. EA on the ipsilateral and contralateral acupoints
      reduced the pain, promoted the recovery of swell, and decreased the positive area
      percentage and mean optical density of GDNF positive cells in the dermal and the
      subcutaneous tissues. However, the non-acupoint EA group did not have this
      action. CONCLUSION: EA can regulate expression of GDNF in local dermal tissue of
      the inflammatory focus in the AA rat, so as to exert the anti-inflammatory and
      analgesic effects.

PMID- 16813190
TI  - [Channels and collaterals are "doctrine" or "theory"].
AB  - OBJECTIVE: To define the concept of meridian theory. METHODS: Characteristics of
      meridian theory were systematically analyzed by the comparison of differences of
      doctrine and theory concepts and according to practicality, abstraction and
      logicality of scientific theory. RESULTS: Meridians have various characteristics
      of scientific theory, so it should be a scientific theory. CONCLUSION: Meridians
      are not a doctrine, but is a scientific theory. That the meridians are defined as
      scientific theory is of important practical significance for studies of meridian
      essence and standardization of acupuncture and moxibustion, and innovation of
      theoretical system of acupuncture and moxibustion.

PMID- 16813189
TI  - [Chief physician Lian Yu-lin's experience on treatment of cervical spondylosis by
      classification].
AB  - In clinical teaching practice of over 30 years, professor LIAN Yu-lin combines
      physiological, pathological and anatomic knowledge with TCM treatment based on
      syndrome differentiation, forming own unique theoretical system. This paper
      introduces LIAN's experience on treatment of cervical spondylosis in detail, and
      location of cervical vertebra three lines and determination of needling depth and
      reinforcing-reducing manipulation based on clinical manifestations of various
      types of cervical spondylosis, and combination of long needle with short needle,
      deep needling with superficially needling, stressing the main point and having a
      definite object. This is an effective pathway for treatment of cervical
      spondylosis.

PMID- 16813191
TI  - [Contributions of Yang Ji-zhou to moxibustion methods].
AB  - YANG Ji-zhou, a famous scientist of acupuncture and moxibustion in the Ming
      Dynasty. He was a great master not only in manipulation methods of acupuncture,
      but also in moxibustion therapy, with unique and profound deep cognition. His
      main contributions include the three aspects: (1) collected a great deal of
      methods and experience of moxibustion treatment from moxibustion physicians and
      gathered and mustered a great works about moxibustion methods before the Ming
      Dynasty; (2) combined with his own clinical experiences, systematized the methods
      and techniques of moxibustion, including the relationship between posture and
      point-fathoming, the treatment orders, the size of moxa cone, the number of moxa
      cones, the techniques of burning moxa, the methods for vesiculation moxibustion,
      etc. forming a more systematic manipulation standard; (3) invented and formed
      YANG's characteristics of clinical moxibustion treatment, i. e selecting a few
      points to dredge the meridian-qi, grasping opportunity of moxibustion, combining
      acupuncture and moxibustion with medicine, and consolidating the therapeutic
      effect by proper diet after treatment.

PMID- 16813193
TI  - [Contemporary problems of occupational diseases].

PMID- 16813192
TI  - [Advances and thinking about prevention and treatment of inflammatory bowel
      diseases by acupuncture and moxibustion].
AB  - OBJECTIVE: To provide scientific foundations for clinical and acupoints
      researches on acupuncture for treatment of inflammatory bowel diseases. METHODS:
      Review the correlated documents of clinical experimental researches issued from
      1995 to 2005, and the clinical and experimental documents about remedy of
      inflammatory bowel diseases by acupuncture and moxibustion were summarized and
      analyzed. RESULTS: Acupuncture and moxibustion had significant therapeutic
      effects on inflammatory bowel diseases, and the studies on the mechanisms have
      achieved some progresses, but the designs and the methods of these studies need
      to be improved. CONCLUSION: Afterwards, the specificity of acupoints, and factors
      of influencing the specificity should be studied via effective diseases treated
      with acupuncture and moxibustion, so as sum up common regularity, rich and
      develop the theory about specificity of acupoints to guide clinical treatment of
      acupuncture and moxibustion.

PMID- 16813194
TI  - [State of autonomous nervous system in vibration disease in miners].
AB  - The authors diagnosed dysfunction of autonomous vascular system with affected
      neuromuscular apparatus, with electrophysiologic polymorphism, degree of nerve
      trunks disorders in miners having concomitant diseases.

PMID- 16813196
TI  - [Serum phospholipids in anthracosilicosis associated with vibration disease].
AB  - The authors studied serum phospholipid subunits in patients with
      anthracosilicosis associated with vibration disease. Findings are significantly
      higher detergent fraction of phospholipids--lysophosphatidylcholine,
      phosphatidylserine, sphingomyelin, lower phosphatidylcholine,
      phosphatidylethanolamine and phosphoinositides--that suggests increased
      transmissivity of biologic membranes and activated inosite mechanism of
      transmembrane signal transmission. Aeroionization appeared to have positive
      influence, normalizing serum phospholipids level.

PMID- 16813195
TI  - [Diagnosis of ischemic heart disease in patients with bronchial asthma caused by
      cytotoxic dust].
AB  - To reveal latent IHD, the authors performed stress testing (veloergometry and
      transesophageal cardiac electric stimulation) in 63 patients with chronic
      obstructive dust bronchitis (CODB) and CODB complicated with bronchial asthma
      varying in severity. Latent IHD was diagnosed in 8% of the patients. Higher
      tolerance of physical exertion was seen in all groups of the patients, except for
      those with severe bronchial asthma--who had lower and medium tolerance. Patients
      with positive veloergometry test performed medium and high level of exertion.

PMID- 16813197
TI  - [Combined influence of chemical and physical factors on health of workers engaged
      into chromium production].
AB  - The authors studied influence of chemical and physical factors in main production
      of chromium compounds plant on the workers' health. Patterns of morbidity
      formation in the workshops are defined.

PMID- 16813198
TI  - [Autoregulation of brain blood flow in dust bronchitis patients with early
      cerebral atherosclerosis].
AB  - The article deals with brain blood flow autoregulation evaluated through
      transcranial Doppler study in dust bronchitis patients with early cerebral
      atherosclerosis in dependence on presence or absence of respiratory failure.
      Present respiratory failure in these patients causes additional disorders in
      brain blood flow autoregulation, especially during a stage of early signs of
      brain circulation insufficiency.

PMID- 16813199
TI  - [Using biologically active supplements to improve psychoemotional state in
      teenagers].
AB  - To improve mental facilities and psychoemotional state in teenagers of
      occupational schools, the authors recommend using biologically active supplements
      during studies.

PMID- 16813200
TI  - [Criteria for premorbid diagnosis of dust diseases in miners].
AB  - The authors defined diagnostic tests describing adaptational resources under
      exposure to dust (RBC resistance to hemolysis and silicon oxide content of
      urine). The testswere studied in apparently healthy miners (shaftmen and mining
      face workers). Results helped to define criteriafor premorbid diagnosis of dust
      diseases via those tests.

PMID- 16813201
TI  - [Structural and functional cardiac changes in patients with chronic dust
      bronchitis associated with arterial hypertension].
AB  - Studies covered structural and functional state of cardiovascular system in
      patients with chronic dust bronchitis associated with arterial hypertension.
      Echocardiographic data helped to specify peculiarities for patients with chronic
      dust bronchitis associated with arterial hypertension in accordance with
      respiratory failure grade.

PMID- 16813202
TI  - [Distribution of heavy metals in organs of experimental animals subjected to dust
      inhalation].
AB  - Biologic substrates of experimental animals characterize mainly overall metals
      intake and could serve as criteria for environmental pollution degree.

PMID- 16813203
TI  - [Combined influence of occupational factors on chronical morbidity parameters
      among female workers of coal-cleaning plants].
AB  - The authors presented hygienic characteristics of work conditions for women in
      coal-cleaning plants, defined priority occupational hazards. Work conditions
      determined structure and prevalence of somatic chronic diseases among major
      occupational groups of female workers.

PMID- 16813204
TI  - [Biochemical and physiologic parameters in experimental animals subjected to
      complex of occupational factors].

PMID- 16813205
TI  - [Combined influence of occupational factors in titanium-magnesium production on
      the workers' functional state].

PMID- 16813207
TI  - [Cutting and incision instruments (II). Incision instruments].
AB  - In a surgeon's tool chest there are a variety of incision-making tools, some of
      frequent, common use in general or specialized surgery such as scalpels or
      scissors. There also exists an abundant quantity of instruments considered to
      pertain exclusively to determined surgical specialties.

PMID- 16813206
TI  - [Serum enzymes in workers of titanium-magnesium enterprise].

PMID- 16813208
TI  - [Now it is possible to teach and evaluate the self-control technique without
      pain].

PMID- 16813209
TI  - [Opiate dependence].

PMID- 16813210
TI  - [We are sexual beings. Sexuality/reproduction pattern. An evaluation and the
      implications for nurses in the mental health field].
AB  - The author pretends to integrate the double-sided aspects of nursing care in the
      mental health field with the specific attention each individual needs as a sexual
      being, since this is an intrinsic factor of human beings. The World Health
      Organization defines sexual health as "the integration of physical, affective,
      intellectual and social aspects of a sexual being, in such a manner that from
      those aspects comes the enrichment and development of human personality,
      communication and love".

PMID- 16813211
TI  - [Chronotherapy in hypertension].
AB  - Arterial blood pressure values measured in a doctor's office are often used as a
      reference at the moment to take decisions regarding a hypertensive patient and
      frequently these values are above the real pressure measurements a patient has
      since these can endure modifications due to multiple factors. Therefore, it is
      necessary to know what can exercise an influence on the control of arterial blood
      pressure measurements and to take advantage of those measurements available to
      professionals in order to obtain the maximum information possible regarding the
      degree of control over those who suffer hypertension.

PMID- 16813212
TI  - [A necessary integration].
AB  - The author reflects about the need to integrate health system professionals with
      the demands of society. The relationships among citizens and health
      professionals, inside the structure of the sanitary system, develop inside a
      global context constituted by society The tendency of the sanitary system to
      increase the power of a biomedical vision and the depersonalization of the
      relationships with patients should lead to a social debate about the desired,
      necessary and sustainable model of health care-nursing. A bio-psycho-social
      concept of health care, an integration of scientific knowledge and the
      incorporation of communicational competencies constitutes one of the challenges
      to be met by a sanitary system which should consider the individual person to be
      its prime reason to exist.

PMID- 16813213
TI  - [Emergency childbirth outside the hospital setting].
AB  - Although not frequently sanitary personnel who form part of the outside the
      hospital walls emergency medical services, the intensive care mobile units or
      ambulance teams, are obliged to attend to emergency childbirths in adverse
      environments and with precarious technical means or means non-specialized means.
      All this requires some special considerations at various levels: parturient,
      fetus and the scene itself. Medical emergency personnel must be prepared to
      diagnose an imminent childbirth in situ and to identify every stage of such a
      birth and its possible complications, while providing integral, yet specific,
      assistance before, during and after childbirth.

PMID- 16813214
TI  - [Meningococcus meningitis nursing intervention from an epidemiological
      perspective].
AB  - Meningitis is an infectious process which can be caused by diverse infectious
      agents. Among these, Neisseria meningitides or meningococcus is the mot relevant
      in our environs due to its high degree of incidence and its mortality; especially
      in recent years, the C sera group is increasing its incidences, particularly in
      children aged one to four so this type of meningitis has become one of the most
      preventive types and therefore, treatable from a nursing perspective. It is
      important to know the epidemiological sequence in order to be able to provide an
      efficient and effective treatment at every stage of its development.

PMID- 16813215
TI  - [Infertility: the magnitude of this problem].
AB  - Infertility affects 10-15% of couples at reproductive ages. At the present times,
      we are experiencing a noticeable increase in the demand for assistance in
      resolving this problem. Over the past two decades, three important changes have
      occurred. First, there was the introduction of assisted fertility reproduction
      techniques which increased the possibilities for effective treatment for
      infertile couples. Secondly, and partially due to the media attention paid to
      these techniques, the general public began to learn about these possible
      treatments which led to a substantial increase in consultations about
      infertility. The third change is the increase in the number of women over age 35
      who solicit medical attention for infertility. This reflects the more advanced
      age at which marriage is consumed and the postponement of pregnancy when women,
      either by choice or out of necessity enroll in the labor market. To all of these
      factors, a slight increase in the proportion of couples considered infertile
      needs be added.

PMID- 16813216
TI  - [Truth is what is useful].
AB  - Recalling a phrase which Buddha said "Truth is what is Useful" the author
      proposes to apply the most appropriate methodology for the research question
      which we deal with in each situation and at every moment.

PMID- 16813217
TI  - [Vector systems of RNA interference].
AB  - RNA interference is a mechanism of posttranslational (at the level of mRNA) gene
      silencing. Sequence-specific mRNA degradation is realized with the help of small
      interfering RNAs produced by processing of a precursor using Dicer, an enzyme
      from the RNAse III family. This mechanism is now widely used in vitro on cultures
      of mammalian cells in order to elucidate functions of individual genes by gene
      specific knockdown. Analogs of small interference RNAs are intensely expressed
      during embryogenesis. The mechanism of RNA interference plays an especially
      important role in embryogenesis of invertebrates. Identification of the functions
      of small noncoding RNAs is essential for understanding the genetic mechanisms
      underlying individual developmental stages. In order to integrate small
      interference RNAs in mammalian cells, various systems have been developed that
      allow both transient (for 48 h) and stable expression in vitro. These systems are
      considered in the present review.

PMID- 16813218
TI  - [Immune proteasomes and immunity].
AB  - A lot of facts that require understanding have been accumulated since immune
      proteasomes were discovered and their relationship with the immune response was
      established. For example, why are immune proteasomes present in all studied
      mammalian organs and tissues, including nonlymphoid tissues? What is responsible
      for differences in the ratio of immune to constitutive proteasomes in different
      organs? Are the functions of immune proteasomes related to the T-cell immune
      response alone, as was shown initially, or not? Are immune proteasomes formed
      simultaneously in different organs during ontogenesis? An attempt is made in this
      review to answer these and other related questions.

PMID- 16813219
TI  - [Individual development and lessons of evolutionism].
AB  - The present crisis of evolutionism was predictable initially, since the
      preformational model of development expressed in the idea of discrete heredity
      contradicts the systemic properties of ontogenesis. Correspondingly, the
      principle of selection of inherited factors cannot explain evolution. The
      synthetic theory based on this principle contains insoluble contradictions in its
      key notions. According to the alternative epigenetic theory based on the
      integrity of living organization, heredity is a product of selection and
      expresses teleonomic direction of development to a stable final state.
      Unification of the genetic concept of evolution with recognition of the integrity
      of development is principally impossible. The cause of dominance of genetic views
      on evolution consists in the correspondence of the mechanistic tradition of the
      18-19th centuries, rather than in their logistic substantiation. For the same
      reason, the biology as a whole is characterized by identification of specific
      linear dependences with the laws of evolution. Following this path in search for
      "new evolutionary synthesis" invites a priori its failure. Evolutionary
      interpretation of genetic generalizations is only possible on the basis of their
      description in terms of development.

PMID- 16813220
TI  - [Centrosome and Golgi complex during differentiation of hepatocytes in early
      postnatal development of mice].
AB  - The structure and functional activity of the centrosome was analyzed in
      hepatocytes of 5-day old mice, as well as the lengths of Golgi complex cistemae.
      In the early postnatal development of mice, the liver was represented by two
      types of hepatocytes: in the first type hepatocytes, the centrosome was active as
      an organizing center of microtubules, while in the second type hepatocytes, it
      was inactive. It was proposed that during ontogenesis the centrosome is
      inactivated as an organizing center of microtubules and activated as an
      organizing center of intermediate filaments characteristic for differentiated
      hepatocytes of adult liver. Morphometry of the Golgi complex has shown that Golgi
      cisternae in the cell center area of early postnatal hepatocytes were longer than
      in the adult hepatocytes and comparable to those in G1-phase hepatocytes of
      regenerating liver. The possibility of relations between the differences in the
      Golgi complex morphology and ontogenetic changes in the functional activity of
      centrosomes is discussed.

PMID- 16813221
TI  - [Effect of hypomorphic mutation in Trithorax-like gene on Drosophila melanogaster
      oogenesis].
AB  - We generated and characterized a new hypomorphic mutation of Drosophila
      melanogaster Trithorax-like (Trl) gene named Trl362. The Trl362 homozygous
      females are sterile and lay a small number of eggs; most embryos die at the early
      developmental stages. The transcriptional Trl level of adult Trl362 females was
      markedly lowered. Little or no GAGA protein, encoded by Trl@, was detected in the
      nurse cell nuclei. The ovaries of Trl362 females showed impairments, such
      considerable changes in the structure of both ovarioles and individual egg
      chambers. We believe that the observed ovarian defects in Trl362 mutants are
      mostly due to a decreased amount of GAGA protein in the germline cells. An
      increase of GAGA-519 protein caused by introduction of hsp83:GAGA-519 transgene
      against Trl362 background rescued partially the female fertility. It may well be
      that a decrease of GAGA protein in Trl362 germline cells leads to a defective
      expression of the genes regulated by transcription factor GAGA, whose products
      are essential for normal Drosophila oogenesis.

PMID- 16813222
TI  - [The rate of oxygen consumption during embryogenesis of Lymnaea stagnalis
      (Gastropoda)].
AB  - We studied the rate of oxygen consumption by the Lymnaea stagnalis embryos. The
      rate of oxygen consumption increased consistently during embryogenesis. The
      volume specific rate of oxygen consumption increased initially from the early
      cleavage stages until the gastrula stage and then decreased gradually to the
      eclosion of snails. There are three periods in embryogenesis of L. stagnalis,
      which differ in the coefficients of allometric dependence between the rate of
      oxygen consumption and volume of embryos: (1) early embryogenesis, when the
      increase in the rate of oxygen consumption is not accompanied by the growth of
      volume of the embryos; (2) larval period (trochophore and veliger stages;
      exponential coefficient k = 0.514), and (3) postlarval period (exponential
      coefficient k = 0.206).

PMID- 16813223
TI  - [Differentiation antigens of hemoblastoses and epithelial tumors: relations to
      the mechanisms of transformation and progression].
AB  - The role of mechanisms underlying differentiation is considered in malignant
      transformation of hemoblastoses and epithelial tumors. In hemoblastoses,
      differentiation is intimately related to malignant transformation and they are
      underlain by the same mechanisms. Immunophenotyping of hemoblastoses is fully
      based on successive stages of their differentiation with characteristic
      expression of differentiation antigens. Unlike hemoblastoses, epithelial tumors
      gradually, in the course of progression, lose their differentiation due to the
      degradation of the connections with the microenvironment, which controls the
      direction and level of epithelial differentiation. Therefore, carcinomas are
      characterized by varying degrees of "antigenic simplification", including the
      epithelial-mesenchymal transition.

PMID- 16813225
TI  - [On preservation and improvement of occupational health of governmental
      employees].
AB  - The authors analyzed social and psychologic features and ecologic and ergonomic
      conditions of governmental employees activities. Relationships between risk
      factors of administrative activities and occupational health were considered. The
      authors designed a complex of requirements for personality traits, psychologic
      and psychophysiologic features and possibilities of governmental employees, that
      determines their fitness for these activities and their occupational success.
      Concept "Preservation and improvement of occupational health of governmental
      employees in 2006-2010" was prepared.

PMID- 16813226
TI  - [Work and health state of working population in Moscow].
AB  - The article shows changes in employed population of Moscow over a period of
      economic changes, in employment structure by economicbranches withsubsequent
      reduction of individuals employed in industrial branches. Based on analysis of
      health parameters of employed population according to official statistics, the
      authors demonstrated trends in those parameters change, with the accent that
      those changes are less negative in Moscow than generally in Russia.

PMID- 16813227
TI  - [Pathogenetic basis for ozone therapy as a modality to treat vibration disease
      (literature review)].

PMID- 16813228
TI  - [Role of lead in arterial hypertension formation (review of literature)].

PMID- 16813229
TI  - [Evaluating individual occupational risk].
AB  - Development of problems connected with individual occupational risk nowadays
      updates improvement of methodic approaches to studies of work conditions
      influence, requires specification in defining main ideas of occupational
      medicine, needs systematization of some theoretic, practical backgrounds and
      solutions to some social and economic problems.

PMID- 16813231
TI  - [Forecasting parameters of acute chemical toxicity according to in vitro
      conformation changes of proteins].
AB  - The authors analyze experimental data on in vitro effects induced by chemicals
      that were used throughout MEIC toxicologic studies in ovalbumin and
      acetylcholinesterase of human RBC. Influence on proteins is compared to acute
      toxicity caused by the chemicals in humans and various cell lines. The conclusion
      is that the method is prospective for screening of acute chemical toxicity signs
      in humans.

PMID- 16813230
TI  - [Markers of asbestos exposure in workers].
AB  - Examination covered 213 workers of asbestos technical ware plant. Standard X-ray
      examination no pulmonary and pleural changes were revealed. External respiration
      studies demonstrated moderate ventilation disorders in half of the examinees: in
      hardware workshop workers--restrictive type disorders, in autofriction components
      workshop workers--obstructive type ones with hyperventilation. Lower diffusing
      lung capacity in one-third of the workers in one of two autofriction components
      workshops proves most likely distributive disorders. Moderately increased serum
      alveolar mucin 3EG5 in 20% of the examinees could be a predictive criterion of
      slow formation of chisotyle pulmonary fibrosis.

PMID- 16813232
TI  - [Health state of sport stars in various kinds of sports].

PMID- 16813233
TI  - [Governmental employee: occupational health and longevity].

PMID- 16813234
TI  - [Russian national sypmposium "Carcinogenic jeopardy in various industries"].

PMID- 16813235
TI  - Young invincibles: insurers look for ways to sell them coverage.

PMID- 16813237
TI  - Using an extraoral pin to place implants in the anterior edentulous or partially
      edentulous mandible.

PMID- 16813238
TI  - [Role of parasitological laboratories in sociohygienic monitoring].
AB  - The data available in the 2003-2004 statutory forms of the Russian Federation's
      subjects show that the parasitological laboratories of state sanitary
      surveillance centers in the Russian Federation make little use of sanitary-and
      parasitological studies during sanitary monitoring. Studies of the
      parasitological indices of foodstuffs, drinking water, wastewater and their
      sediments are not under way in some regions. There is a poor material and
      technical basis in the parasitological laboratories; the work of parasitological
      laboratories does not meet the requirements stipulated in Sanitary Regulations
      1.2.731-99 "Safety of work with microorganisms of pathogenicity groups 3-4 and
      with helmints". Intralaboratory monitoring is not always under way in the
      parasitological laboratories. Highly skilled staff is lacking. It is necessary to
      extend the list of sanitary-and-parasitological studies in accordance with MU
      3.2.1756-03 "Epidemiological surveillance of parasitic diseases".

PMID- 16813239
TI  - [Malaria in Moscow: evaluation of the vulnerability and susceptibility of an
      area].
AB  - Before eradication of malaria in the USSR, there was a steady transmission of
      vivax malaria in the Moscow Region. In the posteradication period, there were two
      insignificant cases of local transmission: in 1972 and 1982. However, since 1999,
      there has been a local transmission of malaria every year. The possible causes of
      the transmission are analyzed. This includes a change in favor of better climatic
      conditions for malaria transmission in 1948 to 2004. It is shown that a weather
      quality jump in about 1984, which appeared as the area's higher susceptibility. A
      great deal of anophelogenic water reservoirs open the way to a local transmission
      in summer months. The vulnerability of the area has increased with a larger
      number of migrants from the endemic areas of the former USSR. Thus, more cases of
      malaria import (increased vulnerability), possibilities of the carrier to
      multiply, better climatic conditions for transmitting malaria (increased
      susceptibility) have created conditions for worsening its situation in the Moscow
      Region.

PMID- 16813241
TI  - [Lanthanide immunofluorescence assay for the serodiagnosis of tick-borne
      encephalitis].
AB  - Lanthanide immunofluorescence assay (LIFA) was used to detect IgM of antibodies
      to tick-borne encephalitis (TBE) virus in 791 patients who had been fallen ill
      with acute febrile diseases in the period of seasonal activity of carrier ticks
      in the endemic region of Russia (the Perm Region) (1786 sera being tested). This
      assay was equally effective as the commercial enzyme immunoassay test system
      (EITS) in the early serological diagnosis of TBE, verifying the clinical
      diagnosis in about 70% of patients just within the first week of disease. At the
      same time, the sensitivity of LIFA was much (nearly 5 times) higher than that of
      EITS in revealing antibody IgM in patients with chronic TBE, as well as in those
      with the acute course of disease, accompanied by the low level and untypical
      trend of accumulation of antibodies ofthis class.

PMID- 16813240
TI  - [Efficiency of KAT-quick P.f. test (KAT medical, SAR) among the populations of
      drug-resistant parasites].
AB  - The KAT-Quick P.f. test (KAT Medical, South African Republic) is based on the
      detection of protein HPR II produced by trophozoites and young gametocytes of P.
      falciparum. This test was conducted by the authors in the distribution areas of
      P. falciparum strains differing in the spectrum of drug resistance. Five hundred
      and forty-nine blood samples from febrile patients in Vietnam (n=84), Sierra
      Leone (n=41), Nigeria (n=14), Tanzania (n=8), Kenya (n=5), and Tadjikistan
      (n=397) were tested. Microscopy served as a primary control. Detection of P.
      falciparum DNA, using polymerase chain reaction (PCR) with included primers
      (nested PCR) of the most sensitive modification of PCR was a final control. The
      efficiency of the KAT-Quick P.f. test was estimated as a ratio of the number of
      its positive results to those of PCR. It was equal to 98-95%. The KAT-Quick P.f.
      test revealed no false-positive case associated with the genome of the parasite.
      The specificity of the test was determined as a ratio of the number of its
      negative (no P. falciparum) results to those of PCR. The blood samples from
      patients with vivax malaria and from those with nonmalarial fever were
      investigated. There was no cross reaction of the KAT-Quick P.f. test system for
      P. falciparum with that for P. vivax. The KAT-Quick P.f. test yielded no positive
      reaction with the blood from patients with non-malarial fever. Drug resistance
      depending on the spectrum of specific drugs caused its emergence may be
      determined by one or several mechanisms that are ultimately determined by one,
      the key mechanism. Thus, the findings suggest that multidrug resistance of P.
      falciparum does not trigger the occurrence of changes in its surface antigen-
      HRPII that is responsible for the efficiency of the KAT-Quick P.f. test. These
      may be also extrapolated to other rapid tests patterned after the same principle.

PMID- 16813242
TI  - [Design of a recombinant antigen for the diagnosis and prevention of larval
      hydatidosis].
AB  - The paper deals with the design of recombinant vector make-ups, with the
      expression of Echinococcus hybrid proteins, and with the study of their
      immunogenic properties. Theoretical rationale is given for the choice of the
      parasitic gene superexpression system (E. coli cells of SG 13009 strain-
      recombinant plasmid pQE/EgF). The authors show that the use ofpolymerase chain
      reaction with oligonucleotide primers homologous to the structures of unique
      genes coding for Echinococcus antigen is promising for the run of the preparative
      quantities of fragments of these genes. They consider the basic stages of
      obtaining hybrid EgF antigen: the isolation of genomic DNA from Echinococcus
      protoscolexes; the run of preparative quantities of an EgF DNA fragment; the
      obtaining of vector pQE plasmid DNA; the design of a recombinant make-up; the
      screening of positive clones; the recombinant plasmid expression of hybrid
      protein and its purification. The commission tests of EgF antigen in enzyme
      immunoassay using 93 human serum samples revealed the following: the sensitivity
      and specificity were 83.8 and 77.4%, respectively. The recombinant protein of EgF
      was found to exert a significant protective action on the development of E.
      multilocularis larvocysts in non-inbred albino mice.

PMID- 16813244
TI  - [Differentiation of the eggs of opisthorchis felineus (Rivolta, 1884) and
      Metorchis bilis (Braun, 1890) by their morphometric signs].

PMID- 16813243
TI  - [The new effective anticestodian agent fluxane].

PMID- 16813245
TI  - [Psycho-autonomic disorders in patients with non-calculous cholecystitis
      concurrent with chronic opisthorchiasis].

PMID- 16813246
TI  - [Ultrasound study of parenchymatous organs in visceral leishmaniasis].
AB  - In the past 5-7 years, there has been an increase in the incidence of visceral
      leishmaniasis. In the available literature we have found no information on the
      use of ultrasound study (USS) in visceral leishmaniasis. This paper characterizes
      the state of parenchymatous organs by USS in patients with visceral leishmaniasis
      before and after a complete course of specific treatment and at convalescence
      that is 10-12 months according to the data of our follow-up.

PMID- 16813247
TI  - [Questionnaire survey of different groups of the population for pediculosis].
AB  - A sociological study of the level of hygienic knowledge in different groups of
      the population (pupils of general educational schools, students of secondary
      specialized and higher educational establishments, teachers of general
      educational schools, parents of the pupils of these schools, employees, workers,
      and unemployed adults), performed, by using the questionnaires for individual
      survey has revealed the inadequate awareness of the medical significance of lice,
      the conditions for the appearance and maintenance of pediculosis, the basic rules
      of the prevention and treatment ofpediculosis among young persons and the fair
      level of adults' knowledge on the above problems, which should be used in
      organizing and doing sanitary educational work among different groups of the
      population in order to enhance its effectiveness.

PMID- 16813248
TI  - [Role of mosquitoes in the transmisson of arboviruses in Armenia].

PMID- 16813249
TI  - [Sanitary-helminthological status of the environment in Yalta].

PMID- 16813250
TI  - [Prevalence of ascariasis in the population of the Republic of Tadjukistan].

PMID- 16813251
TI  - [Improvement of epidemiological surveillance of malaria among frontier guards in
      Tadjukistan].

PMID- 16813252
TI  - [Trichinosis].

PMID- 16813253
TI  - [Food and food industry as a potential biological hazard].

PMID- 16813254
TI  - [Centenary of major dye in parasitology].

PMID- 16813255
TI  - [Ticks are the provision inhabitants that are harmful to human].

PMID- 16813256
TI  - [Recurrence in patients diagnosed with acne treated by isotretinoin and other
      methods].
AB  - Common acne is the most frequently diagnosed dermatosis at the age of
      adolescence. It may lead to psychic disturbances and/or even depression as a
      result of its distinctly visible localization, very long-lasting symptoms, in
      sequela numerous deforming scars or vicious cicatrices. The objective of the
      present paper is to assess recurrences after the treatment of severe acne forms
      in patients treated in the Department of Dermatology in the years 1991-2000, with
      administration of various medications applied locally and/or generally. The
      evaluation of treatment results determined the highest, statistically significant
      difference between the patients subjected to isotretinoin-supported treatment
      process and the locally cured patients. In the group of locally treated patients
      the rate of the acne symptoms recurrence could be observed more often. In the
      remaining groups of patients, no statistically significant differences were
      reported. A little higher acne symptoms recurrence rate is apparent in the group
      of patients locally treated, as compared with that subjected to antibiotics
      supported therapy. A statistically significant relationship between the therapy
      duration with the application of individual methods and the recurrence of illness
      has not been proven as yet. The value of p = 0,5245 proved that there existed no
      relationship between the diagnosis and a period of time elapsed--at the end of
      therapy--since the recurrence of acne disorders has been observed. The longest
      period of remission lasted when inversed acne had been recognized. Recurrence of
      the disease was observed the most rapidly in patients affected with acne
      conglobata. When examining the relationship between the duration of acne symptoms
      recurrence vs. treatment process, statistically significant differences amongst
      the individual applied methods were recorded. In the group A, recurrence of
      illness occurred at a higher rate. A statistically significant relationship
      between the recurrence of signs and symptoms and the initial diagnosis was
      excluded. A higher percentage of recurrence in the groups I, II and III has been
      reported as compared with group V. There is a certain relationship between the
      patient's age and the recurrence of the disease. It mainly referred to the
      elderly. Statistical analysis has proved that there existed significant
      relationship between the recurrence of the disease analysed and the patients'
      sex. A little higher rate of illness occurrence can be observed in a female
      group. The study revealed that recurrences in group of patients treated by
      locally active preparations were observed usually 6 months after the end of
      therapy.

PMID- 16813257
TI  - [Tuberculosis epidemiology in Silesia Voivodship (Poland) between 1994-2004].
AB  - The incidence of tuberculosis in Poland is about 2-3 times higher than average
      for E.U. countries. The aim of this study was to evaluate tuberculosis
      epidemiology in Silesia Voivodship (region where 12% of Polish citizens live)
      against the background of the country (Poland). The paper presents actual TB
      epidemiology situation (incidence, prevalence, morbidity and mortality from TB in
      Silesia and in Poland) as well as its trends observed between 1994-2004. The
      regional incidence in 2004 was 36% lower than in 1994, but 28 per 100,000
      population is still higher than 24.9 per 100,000 observed in Poland. The
      incidence of tuberculosis increases with age, 0.8 in children aged 0-14 years, up
      to 48.0 among 65 and older. In 2004 incidence in the age groups 20-44 and 45-64
      years (23.7 and 46.9 respectively) was much higher than average observed in
      Poland (20.3 and 39.5 respectively), as well the proportion of new cases in this
      age groups. The TB incidence in men (41.7) is 2.6 times higher than in women
      (15.2). Between 1998-2004 in Silesia Voivodship morbidity was growing and in 2004
      was 60.6 per 100,000. In the year 2000 TB mortality was almost two times higher
      in Silesia (4.4) than the average in Poland (2.4). Epidemiological situation of
      tuberculosis in Silesia Voivodship between 1994-2004 improved but is still bad.
      To correct this situation it is necessary to improve the process of fast
      diagnosis and effective therapy.

PMID- 16813258
TI  - [Cost analysis of the treatment of Hodgkin's disease].
AB  - In 80% of cases Hodgkin's disease is curable following standard
      chemotherapeutical regimens. Remaining patients require additional chemotherapy,
      radiotherapy, bone marrow transplantation and even salvage treatment. Patient
      treatment costs during I, II, and subsequent lines of chemotherapy were
      evaluated. Patients were divided into three groups. The first group comprised
      patients who received first-line therapy, and became cured. The second group
      comprised patients who received first-line therapy, did not achieve cure, were
      treated by second-line therapy, which proved successful (in four patients
      including bone marrow transplantation) and were cured afterwards. The third group
      comprised patients who were not cured, despite one administration of consecutive
      treatment regimens. They either are surviving with active disease or they have
      deceased. The total treatment cost was the lowest in 1st group, amounting to the
      average of 8.356 euro. The highest treatment cost was found in group III
      amounting the average of 37.159 euro. Treatment costs were influenced by the
      hospitalization period ((1/3)-(1/2) of the total cost). In the case of disease
      recurrence following autologous bone marrow transplantation, additional
      chemotherapy increased costs to 75.484 euro.

PMID- 16813259
TI  - [Periprosthetic bone remodeling after cementless hip endoprosthesis stem
      implantation].
AB  - The research was aimed at determining the course of the adaptation remodelling of
      the bone tissue basing on the changes in periprosthetic bone density of the THA
      with the employment of the computer densitometric x-ray analysis. The applied
      research methods made it possible to describe the characteristics of the
      adaptation remodelling of the femoral bone tissue around the implanted stem of
      the endoprosthesis and allowed to distinguish the stages included in the course
      of this process: I--the early stage, up to 6 months after an operation,
      characterised by decreasing of the roentgenological bone tissue density and the
      appearance of rarefaction and condensation lines of the bone along the stem, II-
      the late stage, starting 6 months after an operation, with its increasing
      roentgenological bone tissue density, holding back of stem settling, and the
      progression of bone growth and osteointegration led to the establishment of the
      connection between the stem and the surrounding bone tissue. The normal course of
      the adaptation remodelling of the periprosthesis bone tissue is characterised by
      the decrease in the density of bone tissue surrounding the stem, which does not
      exceed 2% of it preoperative value, absence of settling of the stem or its
      nonprogressive settling, and gradual increase in the periprosthesis bone tissue
      taking part not earlier than 6 moths after an operation, which creates conditions
      for osteointegration and establishment of further durable connection between the
      stem and the bone through bone ingrow. An irregular course of the adaptation
      remodelling of the periprosthesis bone tissue is characterised by the decrease in
      bone density after an operation, which does not exceed 5% of its preoperational
      state, followed by the absence of increase in bone density, continuous settling
      of the stem, which does not exceed 3 mm a year, and atrophy of strain within the
      area of the small trochanter and its concentration at the stem level. These
      symptoms are indicative of the disturbance of osteointegration and bone growth
      processes and of a high risk of the aseptic loosening of an endoprosthesis.

PMID- 16813260
TI  - [Arterial hypertension among children and teenagers in the Upper Silesia].
AB  - Nowadays arterial hypertension is more frequently observed among children and
      teenagers then it used to be earlier. Arterial hypertension and obesity are more
      and more often the main sources of atherosclerosis. The purpose of this work was
      to assess the patients with the arterial hypertension treated in the Department
      of Pediatric Cardiology in Katowice in 2003. Patients' age, family history of
      hypertension, family background and parents' education were taken into
      consideration. Birth weight, BMI factor, all the sufferings reported by patients,
      blood pressure measurements results, ABPM, EKG parameters, ECHO+ Doppler
      parameters, exercise test results, fundus of the eye examination, laboratory
      investigation results, were also analyzed. Our results show that a positive
      family history is a very important factor in the development of arterial
      hypertension among children (44.7%). In our patients' cases the most frequent
      clinical symptoms are tachycardia (68%) and obesity (59.2%). In conclusion,
      children and teenagers with hypertension should be successfully treated and those
      with positive family history of hypertension should be taken under primary
      prevention in order to decrease the risk of cardiovascular complications.

PMID- 16813261
TI  - [Oral hygiene in haemodialyzed patients with chronic renal failure].
AB  - The present study aimed to assess the oral hygiene in haemodialyzed patients with
      chronic renal failure (CRF). MATERIAL AND METHODS: 44 haemodialyzed patients with
      CRF were analyzed (18 F and 26 M, mean age 47.4 +/- 1.6). In all patients a
      stomatological examination and dental panoramic x-ray were performed. The
      presence of chronic periodontal disease (CP) and an approximal plaque index (API)
      were assessed. RESULTS: Chronic periodontitis was found in 17 patients (39%),
      whereas in 27 (61%) patients periodontal disease was not present. Oral hygiene
      assessed by API was not satisfactory in 50%, while very good only in 11%
      haemodialyzed patients. Patients with periodontal disease were characterized by
      worse API than patients without periodontitis. CONCLUSION: Oral hygiene status is
      unsatisfactory in most of haemodialyzed uremic patients.

PMID- 16813262
TI  - [Bernard-Soltan technique in surgical treatment of lower lip cancer].
AB  - In Poland lower lip cancer accounts for 0.7% all malignant tumours: 1.3% in men
      and 0.3% in women. In tumours involving more than 1/3 of the lip resection with
      simultaneous reconstruction is necessary. Recommended methods include Bernard
      technique modified by Soltan, Webster technique, and Karapandzic technique. The
      aim of the study was outcome evaluation of surgical treatment of lower lip
      cancer, particularly as a result of Bernard procedure modified by Soltan.
      MATERIAL AND METHODS: 60 patients underwent surgical treatment for lower lip
      cancer between 1994 and 1998. In 25 patients resection with simultaneous lower
      lip reconstruction was made using Bernard technique modified by Soltan. Of them,
      20 patients were followed-up. Sex, age, place of living, clinical TNM stage,
      pathology report and resection radicality, recurrence after radiotherapy, wound
      healing and cosmetic and functional results of surgery were analysed. RESULTS:
      Lower lip cancer involving more than 1/3 of the lip was found in 38.8% men and
      44.5% women. Among 25 patients operated using Bernard-Soltan technique, 40% were
      aged between 70 and 80 years. Twenty (80%) patients were country dwellers. In 60
      patients' group there were 35 (58.33%) with TNM stage I, 56 (93.3%) cases of
      squamous spine cell carcinoma G1. In all 60 patients radicality was achieved. In
      10 patients (16.7%) local recurrence after radiotherapy was treated with surgery.
      Wound suppuration was seen in 3 (12%) patients operated using Bernard-Soltan
      technique and in 1 case (4%) lobe necrosis with salivary fistula also occurred.
      In long-term follow-up lip sensation disorders were reported by 5 patients (mild
      in 3 cases--18.75% and significant in 2 cases--12.5%), speech disorders by 5
      patients (mild in 4 cases--25% and significant in 1 case--6.25%). Saliva leakage
      was observed in 4 patients (mild in 3 cases--18.75% and significant in 1 case-
      6.25%). Cosmetic result was very good in 8 patients (50%), good in 6 patients
      (37.5%) and poor in 2 patients (12.5%). CONCLUSION: In locally advanced lower lip
      cancers surgical treatment using Bernard-Soltan technique results in good both
      early and long-term cosmetic and functional outcomes as well as a good
      oncological radicality.

PMID- 16813263
TI  - [Experiences in the treatment of benign prostatic hyperplasia with high power
      potassium-titanyl-phosphate (KTP) laser].
AB  - Benign prostatic hyperplasia (BPH) exist in about 70% men after 60 years old.
      High power KTP laser is a new tool for the treatment of BPH. MATERIAL AND METHOD:
      49 men were treated by photoselective vaporisation of the prostate (PVP) from
      August 2003 to May 2004. Thirty patients with follow-up period longer than 12
      weeks (12 to 26 weeks) were analyzed. Preoperative prostate volume ranged from 31
      to 136 cc. PSA range, estimated before treatment, was normal in all patients
      (pts). International Prostate Symptom Score (I-PSS) estimated before treatment
      was over 24 and Quality of Life (QoL) was over 3 in all pts. The maximum peak
      urinary flow (Qmax) before treatment ranged from 7.2 to 14.1 ml/s. RESULTS: One
      patient was catheterized with Foley catheter at the finish of the procedure. Two
      pts required catheterization in the first day after treatment. In two pts
      increasing of body temperature to 38 degrees C was observed in the first day
      after treatment. Twenty four hours after treatment haematuria required
      catheterization was observed in one patient. Seven days after treatment in 4 pts
      massive haematuria was observed (two required hospitalisation). In one patient
      because of urinary retention 4 weeks after PVP transurethral resection of the
      prostate was performed. Four weeks after PVP I-PSS decreased from 24 to 20 and
      after 12 weeks to 15. The Qmax increased and ranged from 11.3 ml/s to 17.1 ml/s 4
      weeks after PVP and 12 weeks after PVP ranged from 15.1 to 22.8 ml/s.
      CONCLUSIONS: Photoselective vaporization of the prostate reduces I-PSS in all
      patients 12 weeks after procedure. Short follow-up period and a limited number of
      patients in study group cannot lead to ultimate conclusions. However the results
      encourage to undertaking further studies on PVP for the treatment of BPH.

PMID- 16813264
TI  - [Epidemiology of maxillofacial injuries in athletes].
AB  - The general enthusiasm connected with sports activities causes that we often
      forget about threat connected with careless sports activities. The aim of this
      paper was the evaluation of causes and frequencies of maxillofacial injuries in
      hospitalized athletes in the Department of Maxillofacial Surgery in Katowice.
      Period between 1992-2002 was analyzed. Material consisted of 59 patients in whom
      injury required hospitalization. In studied material the frequency and causes of
      maxillofacial injuries in athletes in eleven-year period was examined. Male and
      female patients were divided in two groups: I--team sports and II--individual
      sports. In analyzed material injuries of upper part of facial skull were not
      affirmed. Injuries of upper facial massif overweighed its bottom massif injuries.

PMID- 16813265
TI  - [Effect of short-term intensive insulin therapy on daily insulin requirement in
      poorly controlled type 2 diabetes patients].
AB  - Prompt metabolic control improvement and daily insulin requirement assessment are
      indications for short-term intensive insulin therapy in type 2 diabetes, applied
      as multiple daily subcutaneous insulin injections (MDI), continuous subcutaneous
      (CSII) and intravenous insulin infusion (IVII). The study aimed at assessing the
      mean daily insulin dosage before beginning and after finishing three methods of
      short-term intensive insulin therapy, discontinued upon achievement of good
      glycemic control. 90 poorly controlled type 2 diabetes patients, hospitalized in
      Diabetology Department of Medical University in Lodz, treated with insulin twice
      daily were enrolled into the study (age 52.8 +/- 6.7 years, mean daily insulin
      dosage 0.76 +/- 0.28 U.I./kg. of body weight, daily blood glucose profile values
      271 +/- 76 mg/dl). The patients were randomized into three groups: the first
      group treated with MDI, the second with IVII and the third with CSII. Insulin
      dosage increased significantly after MDI therapy comparing with prehospital
      values (0.72 U.I./ kg-->0.84 U.I./kg, p = 0.007). No change in daily insulin
      requirement was noted in CSII and IVII groups. We concluded that CSII and IVII
      comparing with MDI are more efficient methods of achieving prompt glucose control
      improvement and they do not lead to the increase in the insulin dosage.

PMID- 16813266
TI  - [Echocardiographic assessment of cor pulmonale in patients with cystic fibrosis].
AB  - Cystic fibrosis (CF) is an inherited multisystem disorder, characterized mainly
      by obstruction and infection of airways and by maldigestion and its consequences.
      An increasing interest concerning patients suffering from CF has been observed.
      Aim of this study was echocardiographic study of morphological structure,
      functional index and the grade of pulmonary hypertension in patients with CF. In
      45 patients aged 3 to 24 years (mean 15.1 years) echocardiography was performed.
      Right ventricular end-diastolic dimension (RVDd) was increased in 67% of
      patients, right ventricular anterior wall thickness (RVAWd) was increased in 71%
      of patients. Pulmonary artery pressure was abnormally high in 84% of CF patients.
      Significant correlations between RVDd, RVAWd, PAP and Shwachman-Kulczycki
      clinical score was found. The dimensions of the left ventricular cavity were
      abnormal in 22% of patients. Insufficiency of pulmonary valve was observed in 47%
      of CF patients and tricuspid insufficiency in 53%. This study demonstrates that:
      1) changes occurs mainly in right ventricle and appear to worsen as the disease
      progresses, 2) all patients with CF should remain under cardiological control, 3)
      echocardiography could be a useful method of long-term monitoring patients with
      CF.

PMID- 16813267
TI  - [Receiving a positive HIV test result--the experience of Polish patients].
AB  - Based on the results of questionnaires, the experience of Polish patients in
      receiving HIV positive results indicating the presence of anti-HIV antibodies was
      evaluated. In spite of the fact that the incidence of doing these tests without
      patient's informed consent has decreased from 61.6% (in the years 1988-1996) to
      27.2% (in the years 1997-2003) it still happens more often that in the other
      "old" countries of EU. The significance of serological window as well as positive
      and negative result is explained too rare to the Polish patients. Most often the
      information is given by the medical doctors who are not enough educated to do it.

PMID- 16813268
TI  - [Analysis of early surgical complications after strumectomy].
AB  - The aim of the study was the analysis of early surgical complications after
      strumectomy. MATERIAL AND METHODS: The study involved 578 patients operated on in
      I Clinic of General Surgery and Transplant at the Medical Academy in Lublin in
      the years 1999-2002. The largest group of the operated patients was the one with
      a non-toxic (neutral) goitre (60.1%). Most of the patients in this group had
      multinodular neutral goitre. The amount of the surgically treated patients
      because of the hyperactive goitre prevailed in this group. RESULTS: Early
      postoperative complications were observe d in 35 cases, which comprise 6.05% of
      the operated patients. On the basis of the obtained results, we stated that there
      are evident differences in the frequency of occurrence of early complications
      depending on the type of the goitre. We concluded that statistically they were
      more frequent in patients operated on because of Graves-Basedov disease as well
      as in patients with Hashimoto goitre (chi2 test p < 0.001). The amount of the
      strumectomy operations conducted annually by a surgeon did not have direct
      influence on the occurrence of the early complications. CONCLUSIONS: Early
      postoperative complications after strumectomy are more frequent in patients
      operated on because of diseases of autoimmunological basis. Operations of the
      thyroid gland and trainings in the surgery of the thyroid gland should take place
      in centers where large amount of such operations are conducted.

PMID- 16813269
TI  - [Upper limb pain and limited mobility in the patients after stroke].
AB  - Pain in the paretic upper limb is a common complaint in the post-stroke patients.
      It usually affects shoulder joint and, less frequently, wrist and hand. Pain is
      usually accompanied by limited mobility of the shoulder and sometimes by swelling
      of the hand and wrist. The aetiology of these complaints remains unclear. The
      objective of the study was to evaluate the incidence of pain, limited mobility,
      swelling and other signs that appear in the paretic limb within the first year
      after stroke. Forty-five stroke patients treated in the Department of Neurology
      in 2000 who answered the questionnaire concerning type, localization and
      intensity of the complaints from paretic upper limb were included. Twenty-six
      patients (58%) had a painful shoulder, wrist or hand. These complaints concerned
      women more frequently than men (71% vs. 46%, consecutively), younger patients
      aged below 55, and those who initially had more severe paresis. Symptoms and
      signs appeared within first month after stroke in majority of patients, and 70%
      of patients considered these symptoms very disturbing, significantly
      deteriorating the dexterity of the paretic limb. Thirty five percent of patients
      complained of limited mobility in the shoulder joint, 18% had incomplete mobility
      of fingers in the paretic limb. Twenty two percent of patients had swollen wrist
      and hand, and 24% had a discoloration and trophic changes of the skin in the
      paretic hand. Cold intolerance by means of freezing sensation in the affected
      limb was experienced by 58% of patients. Three patients had complaints both in
      shoulder and hand, with accompanied swelling, trophic changes and vasomotor
      disturbances in the hand, what fulfilled criteria for the diagnosis of shoulder
      hand syndrome. The results of the study show that upper limb pain and limited
      mobility are common complications of the stroke. Usually underestimated by family
      doctors these symptoms and signs cause a significant discomfort for the patients
      and delay the recovery of the paretic limb.

PMID- 16813271
TI  - [Human oxygen metabolism at high altitudes].
AB  - The rapid tourism development resulted in higher incidence of the diseases
      related to oxygen metabolism pathologies at high altitudes. On the other hand,
      the lack of ability of close monitoring of changes during oxygen breathing in
      these conditions still makes it a subject of high interest for clinical studies.
      It seems that the main problem in oxygen metabolism at high altitudes is the
      disorder of pulmonary oxygen diffusion. In this paper the authors present the
      current knowledge, based on available literature, about the high-altitude oxygen
      metabolism.

PMID- 16813270
TI  - [Drugs used in cardiovascular diseases and cytokines].
AB  - Immunopharmacological studies show that medicines used in cardiovascular diseases
      (atherosclerosis, ischaemic heart disease, heart failure) can exert
      immunomodulatory effects on proinflammatory cytokines. In the paper the influence
      of statins, fibrates, angiotensin converting enzyme inhibitors (ACEI), beta
      blockers, calcium channel blockers and phosphodiesterase inhibitors on the
      activity of cytokines was introduced.

PMID- 16813272
TI  - [Inflammatory concepts of atherosclerosis--clinical utility of C-reactive protein
      measurement].
AB  - According to the current inflammatory concepts of atherosclerosis many
      investigators focus on markers of inflammation, which have been studied in a
      variety of atherosclerotic diseases. C-reactive protein (CRP) is considered of
      particular importance because of its reported function as a sensitive and
      independent marker of vascular inflammation. Clinical utility of its measurement
      seems to be very promising in a prediction of future coronary events and in
      monitoring of coronary heart disease therapy. This article presents laboratory
      and clinical implications of CRP testing in atherosclerosis.

PMID- 16813273
TI  - [Stenting central airways with tracheobronchial stents].
AB  - Tracheobronchial stenting is indicated in the palliative care of cancer patients
      with central airways obstruction due to primary chest and neck tumors, metastatic
      and congenital lesions of these organs. Stents, tubular prostheses, solid or
      wired, removable or not, of different shape, size, material, are used to treat
      airway obstructions due to endobronchial overgrowing, infiltration, compression,
      or relaxation of the airway walls. Silicone stents are well tolerated and
      removable. Their limitations are: the mucociliary clearance impairment, thick
      walls, displacement possibility. Rigid bronchoscopy is required for insertion of
      the prosthesis. Metal stents allow mucociliary transport, exactly match the
      trachea or bronchus dimension and are insertable with the bronchofiberscope.
      Attempts of self-absorbed stents application in the course of
      tracheobronchomalacia and post surgical bronchial wall collapse are being made.
      The choice of the type of the stent used is made on the basis of personnel
      experience, type and localisation of the obstruction, clinical status and
      accompanying diseases.

PMID- 16813274
TI  - [Pathogenesis of chronic obstructive pulmonary disease. Molecular mechanisms
      (part II)].
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality worldwide. Smoking is considered the major cause of the disease.
      Relatively little is known about the molecular mechanisms underlying inflammatory
      response in smokers' lungs and how this relates to the susceptibility to the
      disease, particularly why only 10-15% of smokers develop COPD. Recent development
      in molecular biology techniques allowed the insight into the inner space of the
      cell, to the levels far beyond the reach of the traditional methods. We review
      recent hypotheses on cellular and molecular background of COPD with emphasis on
      the potential role of histone acetylation, as a key modulator of enhanced gene
      transcription responsible for proinflammatory cytokines production in COPD.
      Authors propose a role for modification of nucleosomal structure in inflammatory
      cytokine gene transcription in response to smoking. Cigarette smoke causes
      oxidative stress altering the balance between histone deacetylation and
      acetylation in favor of acetylation. This can contribute to the airflow
      obstruction in smokers susceptible to the development of COPD. Furthermore,
      histone acetylation seems to be a potential mechanism exclusive to smokers with
      susceptibility to COPD based on the transcription of specific pro- and anti
      inflammatory cytokine combinations.

PMID- 16813275
TI  - [Importance of creatine kinase psychiatry--truths and myths].
AB  - Creatine kinase (CK) catalyzes the reversible transfer of the phosphoryl group
      from phosphocreatine to adenosine 5'-diphosphate (ADP), thus regenerating
      adenosine triphosphate (ATP). Creatine kinase genes are expressed in several
      tissues with high, fluctuating energy turnover, e.g. skeletal and cardiac muscle,
      brain and photoreceptor cells, and spermatozoa. Several isoenzymes of CK have
      been characterized: brain-type, muscle-type, and the hybrid isoenzymes, as well
      as the mitochondrial CK isoenzymes. Measurements of serum CK is a routine test in
      the diagnosis of acute myocardial infarction and various muscle disorders.
      Elevation of the serum CK level in psychiatric patients is a fairly nonspecific
      phenomenon. Most commonly, an elevated serum CK level is due to intramuscular
      injections, use of restraints or other intense isometric activity. Although it is
      still controversial, increased CK activity is one of basic criteria of
      neuroleptic malignant syndrome. Despite many studies on the importance of CK in
      postnatal brain and pathogenesis of psychiatric disorders, its role in psychiatry
      remains still mysterious.

PMID- 16813276
TI  - [Precocious puberty and von Recklinghausen's disease].
AB  - Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and
      is characterised by skin, nerve and bone abnormalities. We present a case of von
      Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of
      three cafe au lait spots on the skin and an incranial tumour situated near the
      optic chiasm--qualified as inoperable--were discovered. At the age of 7 first
      signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes
      (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1
      mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to
      LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml
      and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the
      suprasellar region with compression of pituitary stalk. True precocious puberty
      was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9
      years old and has been treated with Diphereline for 16 months. The volume of the
      testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does
      not show any progression in tumour growth. The authors would like to underline
      the need of close observation of children with von Reclinghausen disease with
      regard to possibility of uncovering true precocious puberty which is critical for
      rapid diagnosis and introduction of correct treatment.

PMID- 16813277
TI  - [Skin manifestation of mixed hyperlipidaemia in the course of decompensated
      diabetes].
AB  - The 55-year-old patient was admitted to the hospital ward in a bad condition,
      with some symptoms of dehydration, polydipsia, polyuria, hyperglycaemia and
      slight metabolic acidosis and with numerous xanthomas on the trunk, forearms,
      thighs and buttocks. Moreover he was confirmed to have teeth caries. During the
      treatment the infusion liquids, insulin, metronidasol, amoxiclav, simvastatin
      were administered. The caries teeth extraction was performed. Metabolic
      compensation and disappearance of skin changes was obtained.

PMID- 16813278
TI  - [Late recognition of Kawasaki disease--difficulties in diagnosis].
AB  - Authors describe the case of 4 years old girl with Down syndrome, who was
      operated due to common atrio-ventricular canal and persistent Botalli's duct.
      Intermittent total atrio-ventricular block (without significant bradycardia) has
      been observed one year later and considered as a late postoperative block
      requiring no treatment. Kawasaki disease was diagnosed because of the presence of
      4 out of 6 leading symptoms appearing in typical chronology (fever, mouth and
      throat inflammation, conjunctivitis, erythema with subsequent desquamation of
      skin on palms and feet). ECG revealed total atrio-ventricular block, however with
      significant bradycardia. ECHO showed aneurysms in both coronary arteries.
      Standard treatment of Kawasaki disease was administered (immunoglobulins,
      acetylsalicylic acid) and orciprenalin due to described cardiac block. Pacemaker
      was implanted because of bradycardia. The literature review showed that the
      treatment with immunoglobulins and aspirin can reduce the risk of coronary
      aneurysms development. On the other hand, identification of patients at risk
      coronary aneurysms development is not possible on the ground of biochemical blood
      analysis and physical signs. Thus, all the patients stricken should be treated
      with described above costly drugs (immunoglobulins). Finally, the algorithm of
      procedures in patients with coronary aneurysms was presented.

PMID- 16813279
TI  - [Q fever--case report].
AB  - This work presents a case of Q fever in a 55-year-old man who came back from
      Lebanon. The dominant symptoms of the disease were fever and dry cough and in
      physical testing fine rales at the bottom of the right lung. An epidemiologic
      investigation (a monthly stay in Lebanon) and a serologic testing (indirect
      immunofluorescence assay) were useful to confirm a diagnosis of Q fever. Moreover
      the authors of the work paid attention to the differential diagnosis of Q fever
      and effectiveness of tetracycline in the treatment. The basic methods of the
      prevention of the disease were also described. In the case of a fever in
      individuals coming back from the region of the Mediterranean Sea Q fever should
      be taking into consideration in the differential diagnosis.

PMID- 16813280
TI  - [Idiopathic retroperitoneal fibrosis--the Ormond's disease].
AB  - Idiopathic retroperitoneal fibrosis, so called "Ormond's disease" belongs to rare
      inflammatory processes of unknown etiology. As a result of this disease fibrotic
      masses causing compression of the ureters, vessels and alimentary canal appear in
      the retroperitoneal space. In this study we describe the case of 59 years old
      man. Diagnosis was confirmed with computed tomography of abdominal cavity.
      Patient was treated with corticosteroids, endoxan. Good course of disease was
      observed.

PMID- 16813281
TI  - [Stroke in young woman in the first day after delivery].
AB  - Strokes among young people are not only the most threatening complications of the
      cerebrovascular diseases, but they also lead to considerable disability and
      society' dependency. Among patients under 40 years old heart diseases constitute
      about 18% causes of ischaemic strokes. Other causes of strokes are: artery wall
      dissection, blood clotting disturbances, birth control pills, stimulants (alcohol
      abuse, cigarettes, narcotics), vascular immunological diseases. Among these
      causes there are modifiable factors, which can be eliminated through patients'
      education, change of the lifestyle and proper treatment of diseases. In paper
      there is presented the case of 22-year-old woman, who had in the first hours
      after delivery the paresis of left limbs with paresis of left facial nerve,
      proceded by loss of consciousness and convulsions. In computer tomography (CT)
      and magnetic resonance imaging (MRI) there was extensive angiogenic lesion in the
      area of right internal cervical artery revealed in duplex ultrasonography. In
      transesophageal echocardiography (TEE) there was revealed haemodynamically
      significant patent foramen ovale (PFO). In the patient in ten months after stroke
      there was performed diagnostic cathetarization and then transvascular occlusion
      of PFO using Starflex 28 mm implant. The patient was rehabilitated from the early
      time after stroke. Based on carried out examination results that the most likely
      hypothesis seems to be embolic-thrombotic stroke in the course of hemodynamically
      significant heart defect (paradoxical embolism in patent foramen ovale) revealed
      in drastic way during delivery. The earlier lasted process of dissection of
      cervical internal right artery cannot be also excluded as a cause of stroke.

PMID- 16813282
TI  - [Familial incidence of myelodysplastic syndromes].
AB  - The myelodysplastic syndromes (MDS) are heterogeneous group of clonal disorders
      of hematopoietic stem cells, which manifestation is cytopenia and hypercellular,
      dysplastic bone marrow, often with increased amount of blasts. The pathogenesis
      of majority of MDS remains unexplained. It is regarded that genetic
      predisposition and exposure to toxic environmental agents contribute to genetic
      mutations in MDS. Molecular abnormalities have attracted interest over past years
      because of their presence in most cases of MDS, even without noticeable disorders
      in kariotype. Familial incidence of myelodysplastic syndromes may be helpful in
      understanding genetic factors of the disease. We describe two families in which
      MDS occurred in siblings (3 brothers; sister and brother). Kariotype
      abnormalities have been noted only in one person of each family. The rest of
      patients had a normal kariotype. This suggests that molecular abnormalities are
      the cause of their disease. The occupational exposure to precise mutagens
      (aluminium, greases, diesels, petrol, metals) was noted in two persons in the
      first family and correspondingly in one person in the second. There was absence
      of one mutagen common for every member of two reported families.

PMID- 16813283
TI  - [Patient with haemoptysis, dyspnoea, fever and lung infiltration].
AB  - In this study we presented the case of 55 years old man who was admitted to the
      Dept. of Lung Diseases and Tuberculosis in Zabrze with haemoptysis, dyspnoea,
      fever and lung infiltration. Initially the neoplastic disease was diagnosed. From
      the information gathered from the patient's family it was stated that the patient
      has been taking acenocoumarol for a considerably long time without any
      professional supervision. In this study we emphasize the importance of motivating
      and informing patients about the purposefulness of control examinations while
      using this kind of drugs.

PMID- 16813284
TI  - [Comment to the study: experiences in the treatment of benign prostatic
      hyperplasia with high power potassium-titanyl-phosphate (KTP)].

PMID- 16813285
TI  - [Application of the Dietrych methodology in evaluation of the medical diagnostic
      therapeutic procedures].

PMID- 16813286
TI  - Contour mapping and number of point observations.

PMID- 16813288
TI  - Influence of pollen diet in spring on development of honey bee (Hymenoptera:
      Apidae) colonies.
AB  - The effects of changes in spring pollen diet on the development of honey bee,
      Apis mellifera L. (Hymenoptera: Apidae), colonies were examined in a 3-yr study
      (2002-2004). Pollen-supplemented and pollen-limited conditions were created in
      colonies every spring, and brood rearing and honey yields were subsequently
      monitored throughout the summer. In all 3 yr, colonies that were supplemented
      with pollen or a pollen substitute in the spring started rearing brood earlier
      than colonies in other treatment groups and produced the most workers by late
      April or early May. In 2002, these initial differences were reflected by a two
      fold increase in annual honey yields by September for colonies that were pollen
      supplemented during the spring compared with pollen-limited colonies. In 2003 and
      2004, differences between treatment groups in the cumulative number of workers
      produced by colonies disappeared by midsummer, and all colonies had similar
      annual honey yields (exception: in one year, productivity was low for colonies
      supplemented with pollen before wintering). Discrepancies between years coincided
      with differences in spring weather conditions. Colonies supplemented with pollen
      or a substitute during the spring performed similarly in all respects. These
      results indicate that an investment in supplementing the pollen diet of colonies
      would be returned for situations in which large spring populations are important,
      but long-term improvement in honey yields may only result when spring foraging is
      severely reduced by inclement weather. Beekeepers should weigh this information
      against the nutritional deficiencies that are frequently generated in colonies by
      the stresses of commercial management.

PMID- 16813289
TI  - Effects of honey bee (Hymenoptera: Apidae) and bumble bee (Hymenoptera: Apidae)
      presence on cranberry (Ericales: Ericaceae) pollination.
AB  - Honey bees, Apis mellifera L., are frequently used to pollinate commercial
      cranberries, Vaccinium macrocarpon Ait., but information is lacking on the
      relative contribution of honey bees and native bees, the effects of surrounding
      vegetation on bee visitation, and on optimal timing for honey bee introduction.
      We begin with a descriptive study of numbers of honey bees, bumble bees, and
      other bees visiting cranberry blossoms, and their subsequent effect on cranberry
      yield, on three cranberry properties in 1999. The property surrounded by
      agricultural land, as opposed to wetlands and woodlands, had fewer numbers of all
      bee types. In 2000, one property did not introduce honey bee colonies, providing
      an opportunity to document the effect of lack of honey bees on yield. With no
      honey bees, plants along the edge of the bed had significantly higher berry
      weights compared with nonedge plants, suggesting that wild pollinators were only
      effective along the edge. Comparing the same bed between 1999, with three honey
      bee colonies per acre, and 2000, with no honey bees, we found a significant
      reduction in average berry size. In 2000, we compared stigma loading on
      properties with and without honey bees. Significantly more stigmas received the
      minimum number of tetrads required for fruit set on the property with honey bees.
      Significantly more tetrads were deposited during mid-bloom compared with early
      bloom, indicating that mid-bloom was the best time to have honey bees present.
      This study emphasizes the importance and effectiveness of honey bees as
      pollinators of commercial size cranberry plantings.

PMID- 16813290
TI  - Efficacy of broadcast and perimeter applications of S-methoprene bait on the red
      imported fire ant in grazed pastures.
AB  - The red imported fire ant, Solenopsis invicta (Buren), is a major pest in the
      United States because of its painful sting. Toxic bait has been an important
      management tool against fire ants, but site registrations prohibit applications
      of most baits on grazed pastures. Extinguish, containing the insect growth
      regulator methoprene, was selected for this study because it has a broad site
      registration that includes grazed pastures. The primary objective of this
      research was to evaluate the efficacy for control of red imported fire ants by
      using broadcast applications of methoprene bait at a label rate of 1,121 g/ha
      versus applications around the perimeter of a target area at the reduced rate of
      280 g/ha. Grazed pastures in Lee County, Alabama, and Chambers County, Alabama,
      were selected for this study, with broadcast treatments, perimeter treatments,
      and controls replicated three times at each site. All mounds were counted and
      rated using the USDA population index before applications and then at 8 and 16 wk
      posttreatment. Perimeter applications did not significantly reduce S. invicta
      mound abundance, but bait treatments significantly reduced mound abundance at 16
      wk posttreatment at site 1 where applications were conducted in early evening.
      However, broadcast applications were not effective at site 2 where treatments
      were conducted in early morning with warmer temperatures. Emergence of winged
      alates was observed at 12 wk posttreatment, followed by a high density of
      incipient mounds that may have masked the full treatment effect of methoprene
      applications at site 2. Methoprene bait was effective in reducing abundance of S.
      invicta only when full label rates were applied.

PMID- 16813291
TI  - Effects of three-dimensional and color patterns on nest location and progeny
      mortality in alfalfa leafcutting bee (Hymenoptera: Megachilidae).
AB  - ABSTRACT In alfalfa, Medicago sativa L., seed production where high bee densities
      are released, alfalfa leafcutting bee, Megachile rotundata (F.) (Hymenoptera:
      Megachilidae), females may enter several nesting holes before locating their
      nests. Such levels of "wrong hole" visits lead to an increase in the time spent
      by females locating their own nests, thereby decreasing alfalfa pollination
      efficiency and possibly healthy brood production. The objectives of this study
      were to determine the effect of different nesting board configurations in
      commercial alfalfa leafcutting bee shelters (separating nesting boards, applying
      a three-dimensional pattern to the boards, applying a color contrast pattern, or
      applying a combination of three-dimensional and color contrast patterns) on nest
      location performance, on the incidence of chalkbrood disease, and on the
      incidence of broodless provisions. Separating the nesting boards inside shelters
      improved the ability of females to locate their nests. An increase in nest
      location performance also occurred in boards with the three-dimensional pattern
      and the combined three-dimensional and color contrast pattern, compared with the
      uniform board (a standard configuration currently used commercially). The
      percentage of provisioned cells that were broodless was not statistically
      different between treatments, but the percentage of larvae infected with
      chalkbrood decreased by half in the three-dimensional board design, compared with
      the uniform board.

PMID- 16813292
TI  - Digging behavior of Solenopsis invicta workers when exposed to contact
      insecticides.
AB  - ABSTRACT Contact between ants and insecticides is a prerequisite for contact
      insecticides to be effective in the control of red imported fire ants, Solenopsis
      invicta Buren. Typically, passive contact occurs in the insecticide application
      process, but ants also may actively contact insecticides by digging in treated
      soil or walking on a treated soil surface. Laboratory experiments were conducted
      to determine whether fire ant workers would dig sand treated with contact
      insecticides in two different scenarios: (1) no-choice bioassays where
      insecticide-treated sand was the only available digging substrate, and (2) two
      choice bioassays where nontoxicant sand was also available for digging. Eight
      insecticides that are currently registered in the United States for imported fire
      ant control were tested. They include acephate, bifenthrin, carbaryl, cyfluthrin,
      deltamethrin, gamma-cyhalothrin, permethrin, and pyrethrin. Workers dug the
      treated sand for every insecticide tested, even at concentrations up to 10 times
      of the lowest lethal concentration (LLC) which caused 100% mortality in a
      toxicity bioassay. However, generally, insecticides significantly reduced the
      digging effort, even at a concentration that did not cause any significant
      mortality in the toxicity bioassay.

PMID- 16813293
TI  - Evaluation of a commercially available beneficial insect habitat for management
      of lepidoptera pests.
AB  - A field study was conducted in 2003 and 2004 at the Center for Environmental
      Farming Systems in Goldsboro, NC, to evaluate the effectiveness of a commercially
      available beneficial insect habitat in decreasing pest caterpillar populations in
      organically managed tomato, Lycopersicon esculentum Mill., plots. Six pairs of
      tomato plots were established and a commercial beneficial insect habitat seed mix
      (Peaceful Valley's Good Bug Blend) transplanted around the perimeter of treatment
      plots, whereas a brown-top millet, Brachiaria ramose (L.) Stapf., border was
      planted around control plots. Egg predation, egg parasitism by trichogrammatid
      wasps, and larval parasitism by braconid wasps was monitored throughout the
      growing season to determine whether habitat increased their activity. In both
      years of this study, the density of Helicoverpa zea (Boddie) and Manduca spp.
      eggs was not significantly different between treatment and control plots.
      Although parasitism was the most important component of egg mortality (19-49%),
      parasitism was not significantly different between habitat types. Identifiable
      predation was a minor component (3-9%) of egg fate; it is possible that
      unidentified predation may be part of the approximately 35-52% of eggs that met
      unknown fates. Larval parasitism levels ranged from approximately 10 to 90% but
      was not significantly influenced by the presence of beneficial insect habitat in
      either year of the study. These results demonstrate that natural enemy activity
      in organic tomatoes was not amplified, and pest populations were not reduced by
      the presence of a commercially available beneficial insect habitat.

PMID- 16813294
TI  - Susceptibility of pest Nezara viridula (Heteroptera: Pentatomidae) and parasitoid
      Trichopoda pennipes (Diptera: Tachinidae) to selected insecticides.
AB  - Susceptibility of the southern green stink bug, Nezara viridula (L.)
      (Heteroptera: Pentatomidae), and its endoparasitoid Trichopoda pennipes (F.)
      (Diptera: Tachinidae) to acetamiprid, cyfluthrin, dicrotophos, indoxacarb,
      oxamyl, and thiamethoxam was compared in residual and oral toxicity tests. In the
      residual toxicity test, cyfluthrin, dicrotophos, and oxamyl were highly toxic to
      N. viridula. Thiamethoxam was moderately toxic to these insects. Each of the four
      insecticides was highly toxic to T. pennipes after prolonged tarsal contact with
      dried residues of these chemicals. In the oral toxicity test, where N. viridula
      fed on food covered with insecticide residues, none of the insecticides were
      toxic to adults of this stink bug, but acetamiprid, dicrotophos, and thiamethoxam
      were moderately toxic to the nymphs. In the oral toxicity test, where N. viridula
      fed on a gel-food containing insecticides, cyfluthrin, dicrotophos, oxamyl, and
      thiamethoxam were highly toxic to this stink bug. In an oral toxicity test using
      contaminated sugar water, all of the insecticides were highly toxic to T.
      pennipes. Because insecticides were as toxic, or more toxic, to T. pennipes than
      to N. viridula, it is extremely important to conserve this parasitoid by applying
      these insecticides for control of southern green stink bugs only when the pest
      reaches economic threshold.

PMID- 16813295
TI  - Combined heat and controlled atmosphere quarantine treatments for control of
      western cherry fruit fly in sweet cherries.
AB  - Nonchemical quarantine treatments, using a combination of short duration high
      temperatures under low oxygen, elevated carbon dioxide atmospheric environment
      were developed to control western cherry fruit fly, Rhagoletis indifferens
      Curran, in sweet cherries, Prunus avium (L.). The two treatments developed use a
      chamber temperature of 45 degrees C for 45 min and a chamber temperature of 47
      degreesd C for 25 min, both under a 1% oxygen, 15% carbon dioxide, -2 degrees C
      dew point environment. Both these treatments have been shown to provide control
      of all life stages of western cherry fruit fly while preserving commodity market
      quality. There was no definitive egg or larval stage, which was demonstrated to
      be the most tolerant to either controlled atmosphere temperature treatment system
      treatment. Efficacy tests for both treatments resulted in 100% mortality of >5000
      western cherry fruit flies in each treatment. These treatments may provide, with
      further study, quarantine security in exported sweet cherries where western
      cherry fruit fly is a quarantine concern and fumigation with methyl bromide is
      not desired.

PMID- 16813296
TI  - Container fumigation as a quarantine treatment for Anoplophora glabripennis
      (Coleoptera: Cerambycidae) in regulated wood packing material.
AB  - Anoplophora glabripennis Motschulsky, an Asian cerambicid beetle, was first found
      in the United States in 1996 and was likely introduced into the United States
      through infested wood packing materials and dunnage. Methyl bromide (MeBr)
      fumigation is an internationally accepted treatment for such wood-boring beetles,
      but the use of MeBr is scheduled for reduction or elimination as alternatives
      become available. The use of MeBr can be reduced by more efficient and
      technically sound fumigation techniques, including good circulation and proper
      loading. Concentration x time products (CxT) reported for A. glabripennis in
      solid wood timbers were used to test estimated doses in container fumigations
      conducted in Tianjin and Shanghai, China, during years 2002-2003. We found that
      CxT products observed were generally adequate and would support reduced doses of
      MeBr at temperatures intermediate (10.0 and 15.6 degrees C) to the Animal and
      Plant Health Inspection Service schedule of 80 g and 48 g/m3 at > or =4.4 and >
      or = 21.1degrees C, respectively. The use of fans is recommended, and loading of
      the containers should never reach 100% to allow for better circulation and
      desorption. Proper use of fans will allow for better aeration and increase safety
      to inspectors and consignees of containerized fumigated commodities.

PMID- 16813297
TI  - New restriction fragment length polymorphisms in the cytochrome oxidase I gene
      facilitate host strain identification of fall armyworm (Lepidoptera: Noctuidae)
      populations in the southeastern United States.
AB  - Several restriction sites in the cytochrome oxidase I gene of fall armyworm,
      Spodoptera frugiperda (J.E. Smith), were identified by sequence analysis as
      potentially being specific to one of the two host strains. Strain specificity was
      demonstrated for populations in Florida, Texas, Mississippi, Georgia, and North
      Carolina, with an AciI and SacI site specific to the rice (Oryjza spp.)-strain
      and a BsmI and HinfI site joining an already characterized MspI site as
      diagnostic of the corn (Zea mays L.)-strain. All four of these sites can be
      detected by digestion of a single 568-bp polymerase chain reaction-amplified
      fragment, but the use of two enzymes in separate digests was found to provide
      accurate and rapid determination of strain identity. The effectiveness of this
      method was demonstrated by the analysis of almost 200 adult and larval specimens
      from the Mississippi delta region. The results indicated that the corn-strain is
      likely to be the primary strain infesting cotton (Gossypium spp.) and that an
      unexpected outbreak of fall armyworm on the ornamental tree Paulownia tomentosa
      (Thunb.) Sieb. & Zucc. ex Steud. was due almost entirely to the rice-strain.

PMID- 16813298
TI  - Web-mediated interspecific competition among spider mites.
AB  - Some spider mites, such as Tetranychus spp. and Amphitetranychus spp., create
      complicated webs (CWs), whereas others, such as Panonychus spp., produce little
      webs (LWs). We verified whether interspecific competition occurred between CW and
      LW mites via habitat arrangement under laboratory conditions. The complicated
      webs produced by CW mites clearly inhibited juvenile development in LW mites,
      whereas there was no effect of LW mites on CW mites. In oviposition site choice
      tests, both CW and LW females preferred the lower surface of leaves to the upper
      surface. The preference of LW mites for the lower leaf surface, even in the
      presence of CW mite webs, suggests that the costs of amensalism are outweighed by
      the possible benefits, such as avoiding rain. These findings show that the shift
      in mite species composition from LW to CW mites can occur as a consequence of the
      interspecific association between spider mites via their webs, without pesticide
      applications or the presence of natural enemies.

PMID- 16813299
TI  - Absence of genetic divergence between western corn rootworms (Coleoptera:
      Chrysomelidae) resistant and susceptible to control by crop rotation.
AB  - The western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera:
      Chrysomelidae), is a major pest of corn, Zea mays L., in North America that has
      recently invaded Europe. A loss of ovipositional fidelity to cornfields has
      allowed the species to circumvent crop rotation as a means of control in part of
      its range in the United States. Analyses of variation at eight microsatellite
      loci provided no evidence for general genetic differentiation between samples of
      western corn rootworm collected in soybean, Glycine max (L.) Merr., fields and
      those collected in cornfields both inside and outside the rotation-resistance
      problem area. This result suggests that few or no barriers to gene flow exist
      between rotation-resistant and -susceptible rootworm populations. The
      implications of this result for the management of western corn rootworm in North
      America and Europe are discussed.

PMID- 16813300
TI  - Life tables and development of Bemisia argentifolii (Homoptera: Aleyrodidae) at
      different temperatures.
AB  - The life history of Bemisia argentifolii Bellows & Perring (Homoptera:
      Aleyrodidae) on tomato (Lycopersicum spp.) was studied based on the age-stage,
      two-sex life table at 15, 20, 25, 28, 30, and 35 degrees C. The intrinsic rate of
      increase (r) at these temperatures is -0.0176, 0.0667, 0.1469, 0.1611, 0.1745,
      and 0.0989 d(-1), respectively. The relationship among the gross reproductive
      rate (GRR), the net reproductive rate (R0), and the preadult survivorship (l(a))
      is consistent with GRR > l(a) x GRR > R0 for all results at different
      temperatures. The mean generation time is 81.9, 48.6, 28.4, 25.3, 22.1, and 18.2
      d, respectively. The developmental rate of the egg stage at different
      temperatures fit a linear equation with a thermal summation 89.2 degree-days and
      a developmental threshold of 11.4 degrees C. The developmental rates of the
      nymphal stage fit the model of Stinner et al. and the parameters of C, Rmax, k1
      and k2 were 0.085, 0.0833, 5.298, and -0.263, respectively.

PMID- 16813301
TI  - Mobility of mass-reared diapaused and nondiapaused Cydia pomonella (Lepidoptera:
      Tortricidae): effect of mating status and treatment with gamma radiation.
AB  - Mass-reared insects may differ in their behavioral traits depending on whether
      they have undergone diapause. We studied the mobility of mass-reared diapaused
      and nondiapaused Cydia pomonella (L.) with a focus on understanding the effect of
      mating status and treatment with gamma radiation as these insects are destined
      for use in an areawide program that uses the sterile insect technique (SIT).
      Actograph-measured mobility was assessed one gender at a time for 4 h during
      which the photoperiod transitioned from day to night. We tested 20-30 individuals
      per treatment. For experiments on the effect of mating status, we used 24-48-h
      old adults (diapause [D]-virgin, D-mated, standard [N]-virgin, and N-mated),
      which is the typical age class that is released in the SIT program. Diapaused
      females were significantly more mobile than females reared through standard
      production, whereas no differences were detected in male mobility because of
      rearing strategy. Mated females were significantly more mobile than virgin
      females, whereas no difference in mobility because of mating status was detected
      for males. Mated females were significantly more mobile than mated males. In
      contrast, virgin females were significantly less mobile than virgin males. For
      experiments on the effect of treatment with gamma radiation, adults from all
      rearing strategies and treatments (D-0Gy, D-100Gy, D-250Gy, N-0Gy, N-100Gy, and N
      250Gy), were tested simultaneously. Adult males were tested at two different
      constant temperatures (25 and 20 degrees C), whereas adult females were tested
      only at 25 degrees C. For standard-reared adults, we found a significant linear
      decrease in mobility as the radiation dose increased from 0 to 250 Gy. In
      contrast, the relationship between mobility and dose of radiation was quadratic
      for diapaused males and absent for diapaused females.

PMID- 16813302
TI  - Mobility of mass-reared diapaused and nondiapaused Cydia pomonella (Lepidoptera:
      Tortricidae): effect of different constant temperatures and lengths of cold
      storage.
AB  - Desirable behavioral attributes in mass-reared insects should include the ability
      to perform favorably under the various environmental conditions they encounter
      upon release in the field. Insect quality also may be influenced by storage
      conditions and storage duration before field release. We studied the effects of
      three different constant ambient temperatures (15, 20, and 25 degrees C) and
      different lengths of adult cold storage (0, 24, 48, and 72 h at 2 degrees C) on
      the locomotor activity of adult Cydia pomonella (L.) mass reared through diapause
      or standard production protocols. Mobility was assessed in actographs housed in a
      climate controlled chamber; tests lasted 24 h. We found that adult mobility was
      significantly higher for both males and females at 25 and 20 degrees C than at 15
      degrees C. There were no significant differences in mobility in moths reared
      through diapause or nondiapaused production protocols. In addition, temporal
      analysis of the data revealed a significant shift in the diel patterns of
      activity for both genders when adults were tested at the three different
      temperatures. Moths exposed to the lower temperature shifted their activity
      pattern from evening to mid-afternoon, which may be an adaptive behavior to take
      advantage of the expected warmest period of the day. Diapaused adults were
      significantly less mobile when stored in the cold (24, 48, or 72 h of storage at
      2 degrees C) than were diapaused adults that did not experience cold storage (0
      h). However, length of time in cold storage did not significantly influence the
      mobility of adult codling moths reared through standard production protocols.

PMID- 16813303
TI  - Performance of Lymantria xylina (Lepidoptera: Lymantriidae) on artificial and
      host plant diets.
AB  - Lymantria xylina Swinhoe (Lepidoptera: Lymantriidae) is a serious defoliator of
      hardwood and fruit trees in Taiwan. The larvae of L. xylina feed on >63 species
      of host plants, belonging to 29 families. Because a large number of larvae are
      needed for the production of nucleopolyhedrosis virus (NPV) or other related
      studies, the development of a suitable artificial diet is very important for the
      mass rearing of this moth in the laboratory. In this study, eight artificial
      diets, modified from different formulas, and one host plant, Liquidambar
      formosana Hance, were used to feed L. xylina caterpillars. Through various
      bioassays (first instar survival trial and long- and short-term feeding trials),
      the most suitable diet for the L. xylina was selected by performance comparisons
      with L. formosana. After the first instar survival trial, two of the diets were
      discarded, because no larva survived on these diets. The results of the long-term
      feeding trial indicated that the larvae grew successfully on only three kinds of
      artificial diet. Finally, results of the short-term feeding trial revealed that a
      diet (diet A), modified from the gypsy moth, Lymantria dispar (L.), formula diet,
      was the most appropriate for the L. xylina. Larvae fed on diet A had better
      survival rate, pupal weight, adult size, efficiency of conversion, and relative
      growth rate than larvae fed on other diets; they did not grow as well as those
      fed on L. formosana, however, except for pupal and adult weight, and approximate
      digestibility. In summary, diet A was found to be the best of the artificial
      diets for the L. xylina and is suitable for mass rearing of this moth in the
      laboratory.

PMID- 16813304
TI  - Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae) larval feeding
      behavior on transgenic maize (MON 863) and its isoline.
AB  - Diabrotica species (Coleoptera: Chrysomelidae) larval behavior studies have posed
      a challenge to researchers because of the subterranean life cycle of this pest.
      To fully understand how the western corn rootworm, Diabrotica virgifera virgifera
      LeConte, injures the maize, Zea mays L., root system, its behavior must be
      studied. For example, larvae that can detect an area of the root that has a lower
      amount of toxin, whether from an insecticide or a transgenic maize plant, have an
      increased chance of survival. This study assessed D. v. virgifera larval feeding
      behavior on rootworm-susceptible maize and maize containing a biotechnology
      derived trait (MON 863) with resistance to D. v. virgifera first instar feeding.
      Maize plants were grown in a medium that allowed for direct observation and
      measurements during feeding of larval stadia. Neonates were placed on maize
      seedlings, and data were taken at 3, 6, 9, and 12 d postinfestation on resistant
      and susceptible maize. On rootworm-susceptible maize, neonate larvae aggregated
      at the root tips and began actively feeding, and then they moved to older root
      tissue. Conversely, some larvae that ingested Cry 3Bb1 from the resistant maize
      exhibited no movement. Other larvae on the resistant maize moved continuously,
      sampling root hairs or root tissue but not actively feeding. The continuously
      moving larvae had visibly empty guts, suggesting possible nonpreference for the
      resistant root. This study contributes to our understanding of D. v. virgifera
      larval behavior and provides insight into questions surrounding the potential
      evolution of behavioral and biochemical resistance to Cry3Bb1.

PMID- 16813305
TI  - Cannibalism of Helicoverpa zea (Lepidoptera: Noctuidae) from Bacillus
      thuringiensis (Bt) transgenic corn versus non-Bt corn.
AB  - Because of the importance of cannibalism in population regulation of Helicoverpa
      zea (Boddie) (Lepidoptera: Noctuidae) in corn, Zea mays L., it is useful to
      understand the interactions between Bacillus thuringiensis (Bt) transgenic corn
      and cannibalism. To determine the effects of Bt corn on cannibalism in H. zea,
      pairs of the same or different instars were taken from Bt or non-Bt corn and
      placed on artificial diet in proximity. Cannibalism occurred in 91% of pairs and
      was approximately 7% greater for pairs of larvae reared from Bt transgenic corn
      (95%) than from non-Bt corn (88%). Also, first instar by first instar pairs had a
      lower rate of cannibalism than other pairs. Time until cannibalism was not
      different for larvae from Bt corn versus non-Bt corn. Pupation rate of cannibals
      and surviving victims was not different for pairs from Bt corn versus non-Bt
      corn. Finally, cannibalism increased pupation rate of cannibals from both Bt and
      non-Bt corn by approximately 23 and 12%, respectively, although the increases
      were not significant. Thus, negative effects of Bt on larvae were compensated by
      increased cannibalism in comparison with larvae reared on non-Bt corn, which
      increased larval survival to levels comparable with larvae reared on non-Bt
      plants.

PMID- 16813306
TI  - Role of two insect growth regulators in integrated pest management of citrus
      scales.
AB  - Portions of two commercial citrus orchards were treated for two consecutive years
      with buprofezin or three consecutive years with pyriproxyfen in a replicated plot
      design to determine the long-term impact of these insect growth regulators (IGRs)
      on the San Joaquin Valley California integrated pest management program.
      Pyriproxyfen reduced the target pest, California red scale, Aonidiella aurantii
      Maskell, to nondetectable levels on leaf samples approximately 4 mo after
      treatment. Pyriproxyfen treatments reduced the California red scale parasitoid
      Aphytis melinus DeBach to a greater extent than the parasitoid Comperiella
      bifasciata Howard collected on sticky cards. Treatments of lemons Citrus limon
      (L.) Burm. f. infested with scale parasitized by A. melinus showed only 33%
      direct mortality of the parasitoid, suggesting the population reduction observed
      on sticky cards was due to low host density. Three years of pyriproxyfen
      treatments did not maintain citricola scale, Coccus pseudomagnoliarum (Kuwana),
      below the treatment threshold and cottony cushion scale, Icerya purchasi Maskell,
      was slowly but incompletely controlled. Buprofezin reduced California red scale
      to very low but detectable levels approximately 5 mo after treatment. Buprofezin
      treatments resulted in similar levels of reduction of the two parasitoids A.
      melinus and C. bifasciata collected on sticky cards. Treatments of lemons
      infested with scale parasitized by A. melinus showed only 7% mortality of the
      parasitoids, suggesting the population reduction observed on sticky cards was due
      to low host density. Citricola scale was not present in this orchard, and cottony
      cushion scale was slowly and incompletely controlled by buprofezin. These field
      plots demonstrated that IGRs can act as organophosphate insecticide replacements
      for California red scale control; however, their narrower spectrum of activity
      and disruption of coccinellid beetles can allow other scale species to attain
      primary pest status.

PMID- 16813307
TI  - Influence of fluctuating salinity on insecticide tolerance of two euryhaline
      arthropods.
AB  - Among many other abiotic variations in an estuarine ecosystem, osmotic stress is
      an inescapable part of life. Organisms living in such environments must cope with
      changing osmotic conditions by either behavioral or physiological adaptations.
      Pollutants may increase the physiological stresses that an osmoregulating animal
      may encounter. We have developed a flow-through system that exposes test species
      to insecticides and continuously changing salinity conditions. This system has
      provided an insight into how susceptibility of a species to an insecticide can be
      affected by changing concentrations of salinity. Toxicity tests using this system
      were conducted with two arthropod species that are found in saline habitats:
      mosquito Aedes taeniorhynchus (Wiedemann) and brine shrimp (Artemia sp.). Four
      insecticides-aldicarb, dimethoate, imidacloprid, and tebufenozide-were studied.
      Both species were exposed for 48 h to a concentration of various insecticides
      that would cause 50% of the population to die in hyperosmotic artificial sea
      water (ASW). The mortality rate for both species was more acute in increasing
      salinity (10-200% ASW) than in decreasing salinity (200-10% ASW) conditions. A.
      taeniorhynchus was more susceptible than Artemia when exposed to its hyperosmotic
      LC50 concentration of toxicant while experiencing a change in salinity, e.g.,
      adjusting to a changing salinity decreased the LT50. Our results indicated a
      change in salinity; more importantly, the direction of change altered the
      susceptibility of these organisms.

PMID- 16813308
TI  - Captures of boll weevils (Coleoptera: Curculionidae) in traps associated with
      different habitats.
AB  - Programs to eradicate the boll weevil, Anthonomus grandis grandis Boheman, from
      cotton, Gossypium hirsutum L., in the United States rely heavily on pheromone
      traps for monitoring weevil populations in both active and posteradication
      maintenance programs. Modifications to trapping protocols that increase trap
      effectiveness should contribute to this eradication effort. Between October 1996
      and May 1997 and between September 1997 and April 1998, we compared trap
      effectiveness, indicated by the numbers of captured weevils, in relation to
      selected habitat types. Each study period was divided into fall, winter, and
      spring seasons. Traps were closely associated with seven habitat types, including
      four types with prominent erect vegetation (brush-lined irrigation canal, brush,
      sugarcane, and resaca or ox-bow lake) and three types with only low-growing or
      sparse erect vegetation (irrigation drainage canal, unimproved pasture, and
      fallow fields). Captures of male and female weevils were statistically similar
      regardless of season or trapping habitat. Although captures differed
      significantly among habitats, these differences varied among seasons. Trapping
      habitats with prominent vegetational features generally produced higher weekly
      captures of weevils than habitats lacking these features. Also, captures in traps
      associated with prominent vegetation indicated seasonal differences in weevil
      activity, with highest captures occurring during the fall. Traps associated with
      habitats lacking prominent vegetation did not statistically demonstrate seasonal
      differences. Our results indicate that immediate trap surroundings strongly
      influence the effectiveness of the boll weevil pheromone trap. These results also
      suggest that effectiveness of current trapping programs may be improved through
      purposeful association of traps with selected vegetational features.

PMID- 16813309
TI  - Impact of Eurygaster maura (Heteroptera: Scutelleridae) feeding on quality of
      bread wheat in relation to attack period.
AB  - Sunn pest (or cereal bug) (Heteroptera: Pentatomidae and Scutelleridae)
      infestations of wheat, Triticum aestivum L., in the grain filling stage have the
      potential to adversely affect the quality of harvested grain for bread making. In
      the absence of resistant wheat cultivars, producers must rely on chemical control
      to protect their crop from sunn pest infestations. To implement an efficient
      environment friendly control strategy, there is a need to pinpoint the
      relationships between the timing of the bug attack and gluten degradation. Recent
      outbreaks of Eurygaster maura (L.) in northwestern Italy have increased the local
      concern toward this problem. A 3-yr study was carried out by caging plants of two
      bread wheat cultivars, characterized by different seed texture and bread-making
      quality, and introducing adults of E. maura in four periods corresponding to
      different grain filling stages: heading, early milk-ripe, milk-ripe, and late
      milk-ripe. The degree of bread-making quality depletion was assessed by
      analytical and biochemical methods and related to the attack period. Using
      analysis of variance, significant differences were found in the quality traits of
      kernels attacked by E. maura in different grain filling stages, the maximum
      damage occurring with bug feeding at the late milk-ripe stage. Biochemical
      investigations on gluten confirmed analytical results; in grain samples infested
      at the late milk-ripe stage, SDS gel electrophoresis revealed the degradation of
      some components of the high-molecular-weight glutenins, and high-performance
      liquid chromatography analyses showed a breakdown of the first peak of the
      insoluble fraction, mainly containing polymeric proteins highly related to dough
      strength.

PMID- 16813310
TI  - Incidence of thrips and tomato spotted wilt Tospovirus in fluecured tobacco
      protected from early season insect pest infestations.
AB  - The relative impacts of early season thrips exclusion (cages) and thrips
      suppression (pesticides) on tomato spotted wilt (family Bunyaviridae, genus
      Tospovirus, TSW) Tospovirus infection in flue-cured tobacco, Nicotiana tobaccum
      L., were examined in field trials in 2001-2004. There were fewer TSW symptomatic
      plants when plants were covered by exclusion cages for 6 wk than when they were
      uncaged or caged for 2 or 4 wk after transplanting. Plant height, leaves per
      plant, and total leaf weight per plant were lower in TSW symptomatic plants
      compared with nonsymptomatic plants for the uncaged plus 2- and 4-wk caged
      duration treatments but not different when caged 6 wk. Weekly acephate (Orthene)
      foliar sprays for 2 or 4 wk after transplanting reduced thrips populations for up
      to 5 wk after transplanting, whereas the 6-wk sprays had lower thrips populations
      for up to 8 wk. TSW was lower in both the 4- and 6-wk acephate treatments than in
      the untreated. A tray drench application of imidacloprid (Admire) reduced thrips
      populations in early season plus lowered the percentage of TSW compared with no
      tray drench treatment. The tobacco thrips, Frankliniella fusca (Hinds), was the
      predominate thrips species on tobacco foliage, and 1.9-4.9% tested positive for
      nonstructural TSW protein. The imidacloprid tray drench treatment and 6-wk
      acephate foliar sprays had lower densities of the tobacco-adapted form of Myzus
      persicae (Sulzer). Suppressing early season thrips populations with foliar
      acephate or imidacloprid tray drench are management option that can effectively
      reduce the incidence of TSW in flue-cured tobacco plus suppress aphids.

PMID- 16813311
TI  - An endemic population of western poplar clearwing moths (Lepidoptera: Sesiidae)
      invades a monoculture of hybrid poplar.
AB  - Western poplar clearwing, Paranthrene robiniae (Hy. Edwards) (Lepidoptera:
      Sesiidae), is endemic in Pacific Northwest riparian habitats at low population
      densities. These moths have colonized commercial hybrid poplar (Populus spp.)
      plantings. Moth populations increased rapidly and became a major pest. Trap
      catches of male moths in mid-season surveys increased 190-fold from 95 in 2001 to
      >18,500 in 2002 across 6597 ha of poplars monitored. The outbreak of western
      poplar clearwings was widespread in 2002. Pheromone-baited traps placed one trap
      per 81.75 ha over 13,274 ha of commercial poplars captured >108,000 male moths in
      2002. Damage to commercial poplars included girdling of saplings and burrows in
      limbs and trunks of trees. Repeated applications of chlorpyrifos failed to reduce
      the abundance of moths in 2002. Two management strategies over two separate
      plantations of approximately 6500 ha each were contrasted. Future control
      strategies recommend a halt to the use of contact insecticides that target adult
      moths. Short-term (3-5 yr) control should involve a pheromone-based mating
      disruption strategy followed eventually by selection of a clone that is less
      susceptible to P. robiniae attack.

PMID- 16813312
TI  - Potential of selective insecticides for managing Uraba lugens (Lepidoptera:
      Nolidae) on Eucalypts.
AB  - The leaf skeletonizer Uraba lugens Walker (Lepidoptera: Nolidae), an Australian
      species, locally known as "gumleaf skeletonizer", is well established in New
      Zealand. This insect has the potential to become a serious pest of forestry and
      amenity eucalypts (Eucalyptus spp.) and is the focus of a long-term management
      program. The use of synthetic chemical or biological insecticides is one possible
      control method within an integrated control program. A series of dose-response
      trials were conducted using laboratory bioassays to test the efficacy of several
      insecticides against U. lugens: pyrethroids, spinosad, Bacillus thuringiensis
      kurstaki Berliner (Btk) and an insect growth regulator, Mimic. Pyrethroids and
      spinosad proved highly effective against U. lugens larvae, achieving 100%
      mortality after 3-6-d exposure. The performance of Btk was lower against
      gregarious skeletonizing larvae compared with solitary chewing larvae. When good
      coverage of the target foliage is achieved, >90% mortality is possible with Btk.
      Mimic performed poorly against U. lugens compared with other insecticides tested
      (<60% mortality). The Eucalyptus species on which larvae were feeding
      significantly altered insecticide efficacy. Treatments applied to Eucalyptus
      nitens (Deane & Maiden) Maiden had reduced efficacy compared with E. cinerea F.
      Muell. ex Benth. or E. fastigata Deane & Maiden. Cooler temperatures also reduced
      insecticide efficacy, presumably by decreasing movement and food consumption by
      U. lugens. Recommendations on spray applications to control U. lugens in New
      Zealand are given.

PMID- 16813313
TI  - Effects of cutting date, outdoor storage conditions, and splitting on survival of
      Agrilus planipennis (Coleoptera: Buprestidae) in firewood logs.
AB  - The emerald ash borer Agrilus planipennis Fairmaire (Coleoptera: Buprestidae) is
      an exotic pest of ash (Fraxinus spp.) in North America. We conducted studies in
      Michigan to evaluate how different tree cutting dates, outdoor storage
      conditions, and splitting affected A. planipennis survival in firewood logs. In
      2002-2003, we cut logs from A. planipennis-infested ash trees each month, from
      July to October, and stored half of the logs in shade and half in full sun. In
      2003-2004, we tested logs cut July-December; stored in sun versus shade; tarped
      versus untarped; and whole logs versus split logs. For both years, A. planipennis
      successfully emerged the summer after cutting from logs that represented all
      treatments and all cutting dates tested. Adult emergence density was
      significantly lower in logs cut in July and August. In 2003-2004, A. planipennis
      adult length was significantly shorter, and percentage of mortality was
      significantly higher for logs cut in August compared with later months. Emergence
      density was significantly lower for split logs compared with whole logs for all
      cutting months except for December. There was no significant difference in adult
      emergence density between logs stored in full sun versus shade in 2002-2003. In
      2003-2004, untarped logs in full sun or shade had significantly lower adult
      emergence densities than tarped logs in the sun or shade. In conclusion,
      emergence, survival, and size of A. planipennis was significantly reduced if logs
      were cut early during larval development (July or August); splitting logs and
      storing them untarped in full sun or shade further reduced adult emergence. No
      treatment was 100% effective in preventing adult emergence.

PMID- 16813314
TI  - Identification of the sex pheromone of Copitarsia decolora (Lepidoptera:
      Noctuidae).
AB  - Chemical and electrophysiological analyses and field trials were used to identify
      the female sex pheromone of Copitarsia decolora (Guenee) (Lepidoptera:
      Noctuidae). Coupled gas chromatographic-electroantennographic detection (GC-EAD)
      analysis of the female gland extract showed the presence of two EAD-active peaks,
      which were identified by GC-mass spectrometric (MS) analysis as (Z)-9
      tetradecenyl acetate (Z9-14:Ac) and (Z)-9-tetradecenol (Z9-14:OH). The field
      evaluation of the EAD-active compounds indicated that traps baited with either Z9
      14:Ac or Z9-14:OH caught few males. In contrast, traps baited with the binary
      blend of both components caught significantly more males than traps baited with
      the single compounds. Captures in traps baited with a mixture of Z9-14:Ac and Z9 
      14:OH at 4:1, 10:1, and 100:1 ratios were not significantly different from the
      catches in traps baited with virgin females. Few males were captured in traps
      baited with a blend of Z9-14:Ac and Z9-14:OH at 1:4, 1:10, and 1:100 ratios.

PMID- 16813315
TI  - Alternative management tactics for control of Phyllotreta cruciferae and
      Phyllotreta striolata (Coleoptera: Chrysomelidae) on Brassica rapa in
      Massachusetts.
AB  - The flea beetles Phyllotreta cruciferae (Goeze) and Phyllotreta striolata (F.)
      (Coleoptera: Chrysomelidae: Alticinae) are significant pests of crops in the
      Brassicaceae family. From 2001 to 2003, the efficacy of both new and commonly
      used treatments for the control of flea beetles in brassicas, Brassica rapa L.,
      were evaluated in three small plot, randomized complete block design trials. Row
      cover and carbaryl (applied as a weekly foliar spray) were found to be the most
      consistent at reducing damage in comparison with untreated controls in all
      trials. Two new products that may provide adequate flea beetle control are
      spinosad (in either conventional or organic formulations) and thiamethoxam. The
      plant-derived compounds azidiractin and pyrethrin did not protect treated plants
      from flea beetle feeding. Treatment of plants with kaolin, or removal of the
      beetles with a vacuum, also did not reduce the level of crop damage. The level of
      damage at harvest was found to be correlated with population size of flea beetles
      in each plot, as measured by captures on yellow sticky traps and direct visual
      counts. Removal of the outer two leaves of individual B. rapa plants reduced the
      total number of holes per plant by 40%, while only removing 15% of the leaf area.

PMID- 16813316
TI  - Effect of root feeding by Diaprepes abbreviatus (Coleoptera: Curculionidae)
      larvae on leaf gas exchange and growth of three ornamental tree species.
AB  - Diaprepes abbreviatus L. (Coleoptera: Curculionidae), feeds on a variety of
      ornamental plants grown in southern Florida. Studies were conducted to evaluate
      the effects of root feeding by D. abbreviatus larvae on leaf gas exchange and
      growth of three ornamental tree species commonly grown in southern Florida that
      are known hosts of this weevil: green buttonwood, Conocarpus erectus L.; live
      oak, Quercus virginiana Mill.; and pygmy date palm, Phoenix roebelenii O'Brien.
      These hosts were grown in containers and infested with weevil larvae. Net CO2
      assimilation, transpiration, and stomatal conductance of CO, were measured
      monthly. Leaf, stem, and root fresh and dry weights of each species also were
      determined. In one of two tests, larval root feeding significantly reduced net
      CO2 assimilation, transpiration, and stomatal conductance of CO2 of infested
      green buttonwood trees. Leaf gas exchange of live oak was not affected by larval
      infestation. In addition to testing cumulative effects of multiple infestations
      of larvae, the effects of incremental infestations on leaf gas exchange and fresh
      and dry weights also were tested for each plant species. Net CO2 assimilation,
      transpiration, stomatal conductance of CO2, and dry weights of green buttonwood
      were reduced as a result of larval root feeding, whereas there was no effect of
      incremental larval infestations on leaf gas exchange of live oak or pygmy date
      palm within the experimental time frame. There was no effect of incremental
      larval infestations on dry weights of live oak, but leaf, stem, and dry root
      weight of pygmy date palm were lower for infested plants than for noninfested
      plants. Overall, green buttonwood was more susceptible to larval root feeding
      damage than either live oak or pygmy date palm.

PMID- 16813317
TI  - Assessing Nezara viridula (Hemiptera: Pentatomidae) feeding damage in macadamia
      nuts by using a biological stain.
AB  - Damage caused by southern green stink bug, Nezara viridula (L.), to macadamia
      nuts, Macadamia integrifolia Maiden & Betche, is normally determined after nuts
      are harvested and processed, which may be many months after damage occurred in
      the field. We developed a method using ruthenium red dye to stain stink bug
      feeding probes and indirectly assess feeding activity in macadamia nuts. By using
      the staining method, feeding probes were easily detected on the husk, shell, and
      kernel. Husk probing was highly correlated (0.80-0.90) with feeding and damage to
      the kernel. Failure rate to detect kernel damage from stained husk probes was
      generally <6%. The staining method was equally effective for immature and mature
      nuts; therefore, N. viridula feeding activity can be monitored throughout the
      season to evaluate pest management tactics and forecast outbreak populations.

PMID- 16813318
TI  - Increased tomato yield through pollination by native Australian Amegilla
      chlorocyanea (Hymenoptera: Anthophoridae).
AB  - Amegilla spp. (Hymenoptera: Anthophoridae) have been suggested as potential
      native Australian alternative to overseas used bumblebees (Bombus spp.) for
      pollination of tomato in greenhouses. In this study, we investigate the
      effectiveness of Amegilla chlorocyanea Cockerell as a greenhouse pollinator of
      tomato, Lycopersicon esculentum Mill. We show that (1) a single buzz by a female
      increases tomato weight by 11% compared with pollination by using an industrial
      pollination wand, (2) multiple buzzes increase tomato weight compared with a
      single buzz, and (3) unlimited flower visits lead to an increase in fruit weight
      of 21% compared with wand pollination. These results are comparable with those
      achieved by bumblebee pollination and demonstrate that A. chlorocyanea is a valid
      alternative to bumblebees for greenhouse tomato pollination in Australia.

PMID- 16813319
TI  - Sublethal effects of chronic exposure to tebufenozide on the development,
      survival, and reproduction of the tufted apple bud moth (Lepidoptera:
      Tortricidae).
AB  - The lethal and sublethal effects of tebufenozide on the survival, development,
      and reproduction of a field strain of tufted apple bud moth, Platynota idaeusalis
      (Walker) (Lepidoptera: Tortricidae), were assessed by feeding first and third
      instars tebufenozide-treated diet until pupation. Larval mortality was 27.4 and
      44.7% at 0.1 and 0.2 ppm for first instars and 21.9 and 57.8% at 0.2 and 0.4 ppm
      for third instars, respectively. Treated larvae exhibited higher pupal
      mortalities, lower pupal weights, and generally more deformed adults than
      untreated larvae. Larval development was not affected by tebufenozide when
      neonates were exposed, but development was accelerated slightly at 0.4 ppm for
      both males and females when third instars were exposed. All treatments produced
      sex ratios biased toward males. When paired with either treated or untreated
      males, females resulting from neonates treated at 0.2 ppm and from third instars
      treated at both 0.2 and 0.4 ppm laid from 37 to 65% fewer eggs. A reduction in
      fertility was only found when third instars were treated at the higher 0.4 ppm
      rate. These results suggest that tebufenozide can exhibit a significant effect on
      the population dynamics of the tufted apple bud moth.

PMID- 16813320
TI  - Acaricidal properties of spinosad against Tetranychus urticae and Panonychus ulmi
      (Acari: Tetranychidae).
AB  - Laboratory bioassays were conducted to characterize the activity of the
      insecticide spinosad against the twospotted spider mite, Tetranychus urticae
      Koch, and European red mite, Panonychus ulmi (Koch) (Acari: Tetranychidae). T.
      urticae females and larvae were individually placed on bean, Phaseolus vulgaris
      L. (Fabaceae), leaf disks treated with four rates of spinosad (25, 55, 121, and
      266 ppm) and a water control. Significantly fewer T. urticae completed
      development on any spinosad rates (<15%) compared with the control (>85%),
      whereas spinosad exhibited no significant effects on P. ulmi development; 72.5
      and 83.1% of P. ulmi completed development on apple (Malus pumila P. Mill,
      Rosaceae) leaf disks treated with 75 ppm spinosad and the control, respectively.
      T. urticae adult females placed on spinosad-treated disks had significantly
      higher mortality and lower oviposition rates compared with the water control; no
      significant mortality effects were observed until 3 d after placing adults on
      leaf disks. In choice tests where half of a bean leaf was treated with 55 ppm
      spinosad transversally or longitudinally, T. urticae females were repelled by
      spinosad and largely oviposited and fed on nonspinosad treated areas. Spinosad
      did not affect the behavior of P. ulmi females. When T. urticae females were
      released on potted bean plants (two-leaf stage) in which leaves received spinosad
      sprays on the adaxial or abaxial leaf surfaces, or complete spinosad coverage on
      one or two of the leaves, mite population increase lagged significantly behind
      those released on control plants. These results indicate that spinosad has
      significant acaricidal effects against T. urticae but not P. ulmi.

PMID- 16813321
TI  - Suitability of various turfgrass species and cultivars for development and
      survival of black cutworm (Lepidoptera: Noctuidae).
AB  - Black cutworm, Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae), feeding
      bioassays were conducted on young and mature turfgrass species to determine their
      potential resistance. Measures of resistance included larval weight, survival
      rate, instar development, pupal weight, duration of pupation, and days to
      pupation and adult emergence. Black cutworm reared on Poa pratensis 'Midnight',
      Poa arachnigera 'Tejas', and Poa pratensis X Poa arachnigera 'Reveille' exhibited
      slower development, lower weight, and higher overall mortality than those fed
      upon other turfgrasses tested. Larvae reared on Reveille did not survive to
      pupation and all died within 14 d. Black cutworm larvae reared on Midnight died
      within 17 d in trial 1 but attained pupation in trial 2. However, development of
      black cutworm larvae was slower on Poa pratensis Midnight compared with other
      susceptible turfgrass species such as Agrostis stolonifera 'Penncross', Poa annua
      ('DW194', 'Q98-4-6', and 'Q98-6-18'), Lolium perenne, and Poa supina 'Supranova'.
      Generally, larval performance on young plant tissues was better than on mature
      plant tissues. Larvae reared on P. pratensis 'Midnight' exhibited the most
      distinctive difference on young versus mature plant tissue. These results suggest
      that plant age may play an important role in turfgrass susceptibility and
      resistance.

PMID- 16813322
TI  - Acaricidal activities of extracts of Kochia scoparia against Tetranychus urticae,
      Tetranychus cinnabarinus, and Tetranychus viennensis (Acari: Tetranychidae).
AB  - Extracts of an annual herbaceous plant, Kochia scoparia (L.) Schrad
      (Macrophomina), were bioassayed to determine their acaricidal activities against
      Tetranychus urticae Koch, Tetranychus cinnabarinus (Boisduval), and Tetranychus
      viennensis Zacher (Acari: Tetranychidae) in the laboratory. Extracts had both
      contact and systemic toxicity to these mites. Three solvents were tested for
      preparing crude extracts: petroleum ether, chloroform, and methanol. Methanol was
      the most effective solvent, extracting 3.11-4.53% of the acaricide. Petroleum
      ether was the least effective solvent, extracting 1.25-1.54%. However, extracts
      with chloroform resulted in the highest mite mortality (78.86%), and ultrasound
      assisted extraction required the least time (10 min). Concentrated extracts were
      prepared using chloroform, methyl acetate, or distilled water as a solvent. Mite
      mortalities from the concentrated extracts by methyl acetate or distilled water
      were significantly lower than those by chloroform. The mean lethal concentrations
      (LC50) of the extracts by chloroform, methyl acetate, and distilled water to the
      mites were 0.71 +/- 0.06, 2.08 +/- 0.16 and 8.75 +/- 0.062 mg/ml, respectively.
      After liquid chromatography and thin layer chromatography, the concentrated
      extracts by chloroform were separated into seven groups of isolated fractions and
      tested for acaricidal activity.

PMID- 16813323
TI  - Toxicity, repellency, and transfer of chlorfenapyr against western subterranean
      termites (Isoptera: Rhinotermitidae).
AB  - Chlorfenapyr is a slow-acting insecticide against western subterranean termite,
      Reticulitermes hesperus Banks, when applied to sand. The LD50 at day 7 for
      workers is 29.98 ng per termite and considerably higher than that of chlorpyrifos
      (14.01), cypermethrin (3.21), and fipronil (0.16). Brief exposures to sand
      treated with chlorfenapyr resulted in dose-dependent mortality over a broad range
      of concentrations. Brief 1-h exposures to > or =75 ppm provided >88% kill of
      termites at day 7. Chlorfenapyr deposits did not repel termites, even at 300 ppm.
      Termites tunneled from 0.1 to 1.8 cm into sand treated with 10- to 300-ppm
      chlorfenapyr deposits, resulting in > or =70% mortality. Within 1 h after being
      exposed to 50 ppm chlorfenapyr, approximately 17% of the termites exhibited
      impaired responses to synthetic trail pheromone. By 4 h, nearly 60% of the
      workers were not able to follow a 10 fg/cm pheromone trail. There was a direct
      linear relationship of the uptake of [14C]chlorfenapyr as concentration and
      duration of exposure increased. The percentage of chlorfenapyr transferred to
      recipients varied from 13.3 to 38.4%. Donors exposed for 1 h transferred a
      greater percentage of chlorfenapyr than did donors exposed for 4 h. A 1-h
      exposure on 100-ppm deposits provided sufficient uptake to kill 100% of the
      donors and sufficient transfer to kill 96% of the recipients. There was not
      enough transfer for recipients to serve as secondary donors and kill other
      termites. Horizontal transfer is limited to contact with the original donor and
      by the decreased mobility of workers within 4-8 h after exposure to treated sand.
      The effectiveness of chlorfenapyr barrier treatments is primarily due to its
      nonrepellency and delayed toxicity.

PMID- 16813324
TI  - Survey of metabolic reserves, stored uric acid, and water content from field
      populations of subterranean termites (Isoptera: Rhinotermitidae) from Georgia.
AB  - Total levels of uric acid, soluble proteins, lipid, glycogen, and body water were
      determined for Reticulitermes flavipes (Kollar) workers 24-72 h after field
      collection. In addition, levels of biological molecules were compared for
      termites collected from the same inspection ports within 24 h after field
      collection, and after laboratory captivity of 6 or 9 mo. Uric acid content,
      described in a previous study as steadily accumulating in R. flavipes termites in
      captivity, was found to be low or undetectable in workers tested after 6 or 9 mo
      in the laboratory.

PMID- 16813325
TI  - Comparative study of integrated pest management and baiting for German cockroach
      management in public housing.
AB  - This study assessed the cost and effectiveness of a building-wide cockroach
      integrated pest management (IPM) program compared with bait alone treatment in
      public housing. In total, 12 buildings (66 apartments) were treated and monitored
      for cockroach infestations over 7 mo. The buildings were divided into two groups:
      bait treatment and IPM. Apartments in the bait alone group were treated with
      Maxforce FC Select (0.01% fipronil) during the first 12 wk and Maxforce Roach
      Killer Bait Gel (2.15% hydramethylnon) from 16 wk when necessary. For the IPM
      group, cockroaches were flushed and vacuumed at the beginning of the study;
      sticky traps were placed in all apartments to monitor and reduce cockroach
      numbers; educational materials were delivered to the residents; and Maxforce FC
      Select and Maxforce Roach Killer Bait Gel were applied to kill cockroaches. Two
      seminars were presented to the manger, and Community Service Program staff of the
      Gary Housing Authority to help gain tenant cooperation in the program. Effects of
      the treatments were monitored using sticky traps (six per apartment) at 2, 4, 8,
      12, 16, and 29 wk after treatment. More treatments were applied during each
      monitoring visit when necessary. Those apartments with high levels of
      infestations (> or =12 cockroaches in six traps) before treatment were used to
      compare the IPM and bait only treatments. IPM resulted in significantly greater
      trap catch reduction than the bait treatment. The IPM (n=12) and bait only
      treatment (n=11) resulted in 100.0 and 94.6%, respectively, reduction in trap
      catch after 16 wk. At 29 wk, only one apartment in the IPM group had a high level
      (>12 cockroaches) of cockroach infestation. In contrast, five apartments in the
      bait treatment group had high level infestations at 29 wk based on overnight
      trapping counts; thus, IPM is a more sustainable method of population reduction.
      Sanitation levels in the IPM group significantly improved at 29 wk (n=11)
      compared with that at the beginning of the study. The sanitation levels in the
      bait treatment group remained similar throughout the experiment (n=9). The
      cumulative cost of IPM was significantly higher than that of the bait treatment.
      The median costs per apartment during 29 wk were 64.8 dollars and 35.0 dollars
      for the IPM and bait treatment, respectively. The median amount of bait used per
      apartment in the IPM and bait treatment was 45.0 and 50.0 g, respectively. The
      cost of the IPM group for the 29 wk service was similar to that of the bait
      treatment group. We expect that IPM will provide better control at similar cost
      compared with bait treatment beyond 29 wk.

PMID- 16813326
TI  - Transferof chlorfenapyr among workers of Reticulitermnes flavipes (Isoptera:
      Rhinotermitidae) in the laboratory.
AB  - The potential for transfer of chlorfenapyr among subterranean termites was
      investigated using a donor-recipient (5:95 ratio) experiment. In one experiment,
      workers of Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae) were
      exposed to treated sand at 0, 50, 100, 250, and 500 ppm chlorfenapyr (wt [AI]/wt
      sand). Exposed workers were allowed to interact with untreated nestmates for 14
      d, after which mortality was assessed. The three colonies responded differently
      to the treatments in this experiment. For two colonies, donor exposure rates of
      500 ppm (as well as 250 ppm for colony B) chlorfenapyr resulted in significantly
      greater recipient mortality than controls. For colony C, donor chlorfenapyr
      exposure did not significantly influence recipient mortality. In a second
      experiment examining donor mortality over time, donor termites exposed to all
      test concentrations of chlorfenapyr (except for 0 ppm) suffered 100% mortality
      within 5 d. Analysis of donor termite body washes using gas chromatography
      indicated a linear uptake of chlorfenapyr by termites over the concentration
      range studied. Thus, for this concentration range, no upper limit (saturation
      plateau) of termite uptake for chlorfenapyr was reached.

PMID- 16813327
TI  - Resistance monitoring of Helicoverpa armigera (Lepidoptera: Noctuidae) to bt
      insecticidal protein during 2001-2004 in China.
AB  - Susceptibility of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) field
      populations to the CrylAc toxin of Bacillus thuringiensis Berliner (Bt) were
      monitored from 1997 to 2004 in China. During 2001-2004, 53 strains from the Bt
      cotton planting region were sampled. The range of concentration producing 50%
      inhibition of larval development to third instar (IC50) values among different
      populations in 2001, 2002, 2003, and 2004 was 0.014-0.046, 0.010-0.062, 0.005
      0.062, and 0.005-0.035 microg/ml, respectively. Diagnostic concentration studies
      (IC99) showed that the percentage of individuals reaching third instar ranged
      from 0 to 9.09%, with only four of the 53 tested populations showing values above
      0%. Considering these data, it was determined that the susceptibility to CrylAc
      of the field populations sampled was not different from the baseline in 1997, and
      no movement toward resistance among H. armigera populations was apparent.

PMID- 16813328
TI  - Planting transgenic insecticidal corn based on economic thresholds: consequences
      for integrated pest management and insect resistance management.
AB  - A simulation model of the western corn rootworm, Diabrotica virgifera virgifera
      LeConte, was used to investigate whether sampling and economic thresholds can
      improve integrated pest management (IPM) and insect resistance management (IRM)
      when transgenic insecticidal crops are used for insect pest management. When
      transgenic corn killed at least 80% of susceptible larvae, the calculated
      economic threshold increased linearly as the proportion of susceptible beetles
      surviving the toxin increased. The use of economic thresholds slightly slowed the
      evolution of resistance to transgenic insecticidal crops. In areas with or
      without rotation-resistant western corn rootworm phenotypes, the use of sampling
      and economic thresholds generated similar returns compared with strategies of
      planting transgenic corn, Zea mays L., every season. Because transgenic crops are
      extremely effective, farmers may be inclined to plant transgenic crops every
      season rather than implementing costly and time-consuming sampling protocols.

PMID- 16813329
TI  - Baseline responses of Alphitobius diaperinus (Coleoptera: Tenebrionidae) to
      cyfluthrin and detection of strong resistance in field populations in eastern
      Australia.
AB  - Resistance to cyfluthrin in broiler farm populations of lesser mealworm,
      Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), in eastern Australia
      was suspected to have contributed to recent control failures. In 2000-2001,
      beetles from 11 broiler farms were tested for resistance by comparing them to an
      insecticide-susceptible reference population by using topical application.
      Resistance was detected in almost all beetle populations (up to 22 times the
      susceptible at the LC50), especially in southeastern Queensland where more
      cyfluthrin applications had been made. Two from outside southeastern Queensland
      were found to be susceptible. Dose-mortality data generated from the reference
      population over a range of cyfluthrin concentrations showed that 0.0007%
      cyfluthrin at a LC99.9 level could be used as a convenient dose to discriminate
      between susceptible and resistant populations. Using this discriminating
      concentration, from 2001 to 2005, the susceptibilities of 18 field populations
      were determined. Of these, 11 did not exhibit complete mortality at the
      discriminating concentration (mortality range 2.8-97.7%), and in general,
      cyfluthrin resistance was directly related to the numbers of cyfluthrin
      applications. As in the full study, populations outside of southeastern
      Queensland were found to have lower levels of resistance or were susceptible. One
      population from an intensively farmed broiler area in southeastern Queensland
      exhibited low mortality despite having no known exposure to cyfluthrin.
      Comparisons of LC50 values of three broiler populations and a susceptible
      population, collected in 2000 and 2001 and recollected in 2004 and 2005 indicated
      that values from the three broiler populations had increased over this time for
      all populations. The continued use of cyfluthrin for control of A. diaperinus in
      eastern Australia is currently under consideration.

PMID- 16813330
TI  - Investigation of resistance mechanisms to fipronil in diamondback moth
      (Lepidoptera: Plutellidae).
AB  - The SZ-F strain of Plutella xylostella (L.) (Lepidoptera: Plutellidae) was
      derived from a field-collected strain (SZ) by 20 generations of continuous
      selection with fipronil. The selection resulted in 300-fold increase in
      resistance to fipronil, and 3.5- and 6.5-fold cross-resistance to dieldrin and
      endosulfan, respectively, in the SZ-F strain compared with the unselected SZ
      strain. Analysis of detoxification enzyme activities and bioassay with synergists
      indicated that metabolic mechanisms are not important to fipronil resistance of
      the SZ-F strain and that the fipronil resistance is most likely attributed to
      target site insensitivity. The genomic DNA fragments flanking the second membrane
      spanning region of Rdl gamma-aminobutyric acid (GABA) receptor gene from P.
      xylostella, PxRdl, were cloned and sequenced. A single allele of the PxRdl gene
      (encoding A302 or allele PxRdl-Ala) was found in both the Roth (susceptible) and
      SZ strains. In addition to the wild-type allele PxRdl-Ala, the resistant SZ-F
      strain carried a mutant PxRdl allele with the conserved amino acid replacement
      A302(GGC)--> S302(TCC) (allele PxRdl-Ser). The mutant PxRdl-Ser allele frequency
      in the SZ-F strain was 30%. After treatment of 20 mg/l fipronil on the SZ-F
      strain, the PxRdl-Ser allele frequency in the survivors increased to 57%. High
      frequency of the PxRdl-Ala allele remaining in the resistant SZ-F strain
      suggested that the A302S mutation in the PxRdl gene is partially associated with
      fipronil resistance and that other mutation(s) in the PxRdl gene or other Rdl
      like subunit(s) may contribute to fipronil resistance.

PMID- 16813331
TI  - Effect of entomopathogenic nematodes on the fitness cost of resistance to Bt
      toxin crylac in pink bollworm (Lepidoptera: Gelechiidae).
AB  - The widespread use of crop plants genetically engineered to produce toxins from
      the bacterium Bacillus thuringiensis (Bt) imposes selection on insect populations
      to evolve resistance. The pink bollworm, Pectinophora gossypiella (Saunders)
      (Lepidoptera: Gelechiidae), is a major pest of cotton in the southwestern United
      States that is currently controlled with transgenic cotton that produces Bt toxin
      Cry1Ac. Previously reported theoretical work suggests that, in conjunction with a
      high dose/refuge strategy, fitness costs of Bt resistance can slow or prevent the
      evolution of resistance. We report here that the entomopathogenic nematode
      Steinernema riobrave (Rhabditida: Steinernematidae) increased the fitness cost of
      resistance to Cry1Ac in P. gossypiella. Mortality of P. gossypiella from fourth
      instar to adult eclosion was significantly higher for a Bt-resistant strain than
      a susceptible strain in tests with two to 14 infective juveniles of S. riobrave
      per larva, but it did not differ between strains when nematodes were absent.
      Nematodes established in P. gossypiella larvae at all concentrations tested, and
      nematode reproduction in infected P. gossypiella larvae occurred at nematode
      concentrations of four to 14 infective juveniles per larva. Our results suggest
      that incorporation of entomopathogenic nematodes into an integrated resistance
      management strategy could help to delay pest resistance to Bt toxins.

PMID- 16813332
TI  - Effect of Bacillus thuringiensis cry3Bb1 protein on the feeding behavior and
      longevity of adult western corn rootworms (Coleoptera: Chrysomelidae).
AB  - The first transgenic corn hybrids expressing the Bacillus thuringiensis (Bt)
      Cry3Bb1 protein to control corn rootworm (Diabrotica spp.) larvae were registered
      for commercial use in 2003. This study was conducted to investigate the effect of
      Cry3Bb1 protein in combination with a cucurbitacin bait on adult feeding and
      longevity of both organophosphate-resistant and -susceptible western corn
      rootworms, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae). In
      choice and no-choice tests, possible repellency to the Bt protein was quantified
      by comparing beetle consumption of cellulose disks treated with three
      concentrations of Bt in combination with a feeding stimulant (Invite EC) to disks
      treated with stimulant alone. A lethal-time assay also was conducted to examine
      survival of beetles exposed to Bt protein in their diet. Results from these
      assays indicate that adult rootworms are not significantly deterred by the
      presence of Cry3Bb1 on the treated discs and that ingestion of toxin does not
      adversely affect adult longevity.

PMID- 16813333
TI  - Development of resistance to spinosad in oriental fruit fly (Diptera:
      Tephritidae) in laboratory selection and cross-resistance.
AB  - In this study, we assessed the potential for the development of resistance to the
      insecticide spinosad in a laboratory colony of the oriental fruit fly, Bactrocera
      dorsalis (Hendel) (Diptera: Tephritidae). Resistance was selected by using
      topical applications of spinosad. After eight generations of selection, the LD50
      of the selected line was 408 times greater compared with that of the untreated
      parental colony. This spinosad-resistant line did not exhibit cross-resistance to
      10 other insecticides tested, including six organophosphates (naled, trichlorfon,
      fenitrothion. fenthion, formothion, and malathion) one carbamate (methomyl), and
      three pyrethroids (cyfluthrin, cypermethrin, and fenvalerate). However, using
      lines previously selected for resistance to these same insecticides, two of the
      10 lines tested (naled- and malathion-resistant) did show some cross-resistance
      to spinosad. Also, oriental fruit flies from different field collections where
      naled and malathion have been used for control purposes displayed some resistance
      to spinosad. In addition, the effects of direct ingestion of spinosad through
      dietary supplementation also were tested. Overall, the laboratory resistance and
      cross-resistance data developed in this study provide new information that will
      be useful for managing the development of resistance when spinosad is used to
      control B. dorsalis in the field.

PMID- 16813334
TI  - Differences in susceptibility and physiological fitness of Mexican field
      Trichoplusia ni strains exposed to Bacillus thuringiensis.
AB  - The use of different commercial Bacillus thuringiensis (Bt) products in the Bajio
      guanajuatense area in Mexico began 12 yr ago, and resistance to Bt in this area
      has been reported for Plutella xylostella (L.) The current study provides a
      baseline response and resistance potential to Bt in field and laboratory strains
      of Bajio Trichoplusia ni (Hubner). Differences in susceptibility to Bt among T.
      ni populations were observed. T. ni neonates collected in Romita, Guanajuato,
      were more susceptible to Bt than those collected in Salvatierra or San Luis de la
      Paz, Guanajuato. After five generations of exposure to XenTari in the laboratory,
      decreased susceptibility was found only in the Salvatierra insects, with an LC50
      that was 2.1-fold greater than that of a Mexican laboratory strain. The XenTari
      selected San Luis de la Paz strain was from 16- to 87-fold more resistant to
      CrylA protoxins than U.S. (US) and Mexican laboratory strains. Although CrylAb is
      not a component of XenTari, this strain also was significantly less susceptible
      to CrylAb toxin compared with a US strain, with a resistance ratio of 40.4. The
      larval weights and lengths, pupal lengths, and percentage of pupation were
      significantly lower for the Salvatierra strain than for all other strains. The
      relationship of T. ni susceptibilities to Bt Cry toxins and protoxins after
      several generations of exposure to XenTari and its similarity to P. xylostella
      behavior.

PMID- 16813335
TI  - Effect of resistance to Bacillus thuringiensis cotton on pink bollworm
      (Lepidoptera: Gelechiidae) response to sex pheromone.
AB  - Fitness costs associated with resistance to transgenic crops producing toxins
      from Bacillus thuringiensis (Bt) could reduce male response to pheromone traps.
      Such costs would cause underestimation of resistance frequency if monitoring was
      based on analysis of males caught in pheromone traps. To develop a DNA-based
      resistance monitoring program for pink bollworm, Pectinophora gossypiella
      (Saunders) (Lepidoptera: Gelechiidae), we compared the response to pheromone
      traps of males with and without cadherin alleles associated with resistance to Bt
      cotton (Gossypium hirsutum L.). When irradiated males from two hybrid laboratory
      strains with an intermediate frequency of resistance alleles were released in
      large field cages, the probability of capture in pheromone traps was not lower
      for males with resistance alleles than for males without resistance alleles.
      These results suggest that analysis of trapped males would not underestimate the
      frequency of resistance. As the time males spent in traps in the field increased
      from 3 to 15 d, the success of DNA amplification declined from 100 to 30%. Thus,
      the efficiency of a DNA-based resistance monitoring program would be improved by
      analyzing males remaining in traps for 3 d or less.

PMID- 16813336
TI  - Multiple resistance and biochemical mechanisms of pyridaben resistance in
      Tetranychus urticae (Acari: Tetranychidae).
AB  - A field colony of Tetranychus urticae (Koch) (Acari: Tetranychidae) resistant to
      pyridaben was selected with pyridaben successively for 20 generations to produce
      the PR-20 strain. Resistance and multiple resistance levels of the PR-20 strain
      to 15 acaricides were determined using a spray bioassay. The PR-20 strain was
      extremely resistant to pyridaben (resistance ratio [RR] = 240]. The strain
      exhibited extremely strong resistance to fenpyroximate (RR=373) and acrinathrin
      (RR=329) and strong resistance to benzoximate (RR=84). An RR = 10-40 was observed
      with abamectin, fenazaquin, fenbutatin oxide, fenpropathrin, and tebufenpyrad.
      The PR-20 strain showed low levels of resistance (RR <10) to azocyclotin,
      bromopropylate, chlorfenapyr, dicofol, milbemectin, and propargite. Synergist
      experiments with different metabolic inhibitors revealed that piperonyl butoxide
      (PBO), a mixed function oxidase (MFO) inhibitor, had the greatest effect on
      pyridaben resistance. PBO significantly caused pyridaben resistance in the PR-20
      strain to drop to the full susceptibility level of the susceptible (S) strain.
      However, there was no significant difference in MFO activities measured using a
      model substrate between the S and PR-20 strains. These results suggest that use
      of certain acaricides with little multiple resistance or PBO will be useful for
      the management of pyridaben resistance in the field.

PMID- 16813337
TI  - Biotypic diversity in greenbug (Hemiptera: Aphididae): characterizing new
      virulence and host associations.
AB  - Biotypic diversity of the greenbug, Schizaphis graminum (Rondani) (Hemiptera:
      Aphididae), was assessed among populations collected from cultivated wheat,
      Triticum aestivum L., and sorghum, Sorghum bicolor (L.) Moench, and their
      associated noncultivated grass hosts. Greenbugs were collected during May through
      August 2002 from 30 counties of Kansas, Nebraska, Oklahoma, and Texas.
      Discounting the presumptive biotype A, five of the remaining nine letter
      designated greenbug biotypes were collected; however, biotypes C, F, J, and K
      were not detected. Biotypes E and I exhibited the greatest host range and were
      the only biotypes collected in all four states. Sixteen greenbug clones,
      collected from eight plant species, exhibited unique biotype profiles. Eleven
      were collected from noncultivated grasses, three from wheat, and two from
      sorghum. The most virulent biotypes were collected from noncultivated hosts. The
      great degree of biotypic diversity among noncultivated grasses supports the
      contention that the greenbug species complex is composed of host-adapted races
      that diverged on grass species independently of, and well before, the advent of
      modern agriculture.

PMID- 16813338
TI  - Sugarcane borer (Lepidoptera: Crambidae) management threshold assessment on four
      sugarcane cultivars.
AB  - This research assesses the potential for using different economic injury
      thresholds in management of a key insect pest on susceptible and resistant
      commercially produced cultivars of sugarcane (Saccharum spp. hybrids). In a 2-yr
      sugarcane borer, Diatraea saccharalis (F.) (Lepidoptera: Crambidae), study
      involving four commercially produced sugarcane cultivars and four insecticide
      treatment thresholds, 'LCP 85-384' and 'HoCP 91-555' were the most susceptible
      based on percentage of bored internodes compared with the more resistant 'HoCP 85
      845' and 'CP 70-321'. In 2001, the 10% infested stalks threshold was not as
      effective as the 5% early season-10% late season and 5% full season for HoCP 91
      555. Based on D. saccharalis injury under natural infestation conditions,
      susceptible cultivars seem to require a lower infestation threshold than the more
      resistant cultivars to achieve adequate injury reduction. Among yield components,
      only the theoretical recoverable sugar per stalk was significantly increased by
      applying insecticides. With the resistant HoCP 85-845, differences were not
      detected for percentage of bored internodes among treated versus untreated
      management regimes. The resistant HoCP 85-845 had higher levels of fiber in our
      study; however, no clear pattern on resistance mechanisms was established,
      because the resistant cultivar CP 70-321 had comparatively low levels of fiber.
      The development of cultivar-specific thresholds is expected to lower the amount
      of insecticide used for D. saccharalis management in the sugarcane industry,
      reduce selection pressure, and delay the development of insecticide resistance.

PMID- 16813339
TI  - Responses of Nasonovia ribisnigri (Homoptera: Aphididae) to susceptible and
      resistant lettuce.
AB  - Nymphs and alates of aphid Nasonovia ribisnigri (Mosley) (Homoptera: Aphididae)
      were tested on 10 lettuce cultivars with N. ribisnigri resistance gene Nr and 18
      cultivars without the resistance gene in various bioassays. Bioassays used whole
      plants, leaf discs, or leaf cages to determine susceptibility of commercial
      lettuce cultivars to N. ribisnigri infestation and to evaluate screening methods
      for breeding lettuce resistance to N. ribisnigri. Resistant and susceptible
      plants were separated in 3 d when using whole plant bioassays. Long-term (> or =7
      d) no-choice tests using leaf cages or whole plants resulted in no survival of N.
      ribisnigri on resistant plants, indicating great promise of the Nr gene for
      management of N. ribisnigri. Effective screening was achieved in both no-choice
      tests where resistant or susceptible intact plants were tested separately in
      groups or individually and in choice tests where susceptible and resistant plants
      were intermixed. Leaf discs bioassays were not suitable for resistance screening.
      All lettuce cultivars without the resistance gene were suitable hosts for N.
      ribisnigri, indicating the great importance of this pest to lettuce production
      and the urgency in developing resistant lettuce cultivars to manage N.
      ribisnigri.

PMID- 16813340
TI  - Prediction of global distribution of insect pest species in relation to climate
      by using an ecological informatics method.
AB  - The aim of this work was to predict the worldwide distribution of two pest
      species-Ceratitis capitata (Wiedemann), the Mediterranean fruit fly, and
      Lymantria dispar (L.), the gypsy moth-based on climatic factors. The distribution
      patterns of insect pests have most often been investigated using classical
      statistical models or ecoclimatic assessment models such as CLIMEX. In this
      study, we used an artificial neural network, the multilayer perceptron, trained
      using the backpropagation algorithm, to model the distribution of each species.
      The data matrix used to model the distribution of each species was divided into
      three data sets to (1) develop and train the model, (2) validate the model and
      prevent over-fitting, and (3) test each model on novel data. The percentage of
      correct predictions of the global distribution of each species was high for
      Mediterranean fruit fly for the three data sets giving 95.8, 81.5, and 80.6%
      correct predictions, respectively, and 96.8, 84.3, and 81.5 for the gypsy moth.
      Kappa statistics used to test the level of significance of the results were
      highly significant (in all cases P < 0.0001). A sensitivity analysis applied to
      each model based on the calculation of the derivatives of each of a large number
      of input variables showed that the variables that contributed most to explaining
      the distribution of C. capitata were annual average temperature and annual
      potential evapotranspiration. For L. dispar, the average minimum temperature and
      minimum daylength range were the main explanatory variables. The ANN models and
      methods developed in this study offer powerful additional predictive approaches
      in invasive species research.

PMID- 16813341
TI  - Operating characteristics of full count and binomial sampling plans for green
      peach aphid (Hemiptera: Aphididae) in potato.
AB  - Counts of green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae), in
      potato, Solanum tuberosum L., fields were used to evaluate the performance of the
      sampling plan from a pest management company. The counts were further used to
      develop a binomial sampling method, and both full count and binomial plans were
      evaluated using operating characteristic curves. Taylor's power law provided a
      good fit of the data (r2 = 0.95), with the relationship between the variance (s2)
      and mean (m) as ln(s2) = 1.81(+/- 0.02) + 1.55(+/- 0.01) ln(m). A binomial
      sampling method was developed using the empirical model ln(m) = c + dln(-ln(1 -
      P(T))), to which the data fit well for tally numbers (T) of 0, 1, 3, 5, 7, and
      10. Although T = 3 was considered the most reasonable given its operating
      characteristics and presumed ease of classification above or below critical
      densities (i.e., action thresholds) of one and 10 M. persicae per leaf, the full
      count method is shown to be superior. The mean number of sample sites per field
      visit by the pest management company was 42 +/- 19, with more than one-half (54%)
      of the field visits involving sampling 31-50 sample sites, which was acceptable
      in the context of operating characteristic curves for a critical density of 10 M.
      persicae per leaf. Based on operating characteristics, actual sample sizes used
      by the pest management company can be reduced by at least 50%, on average, for a
      critical density of 10 M. persicae per leaf. For a critical density of one M.
      persicae per leaf used to avert the spread of potato leaf roll virus, sample
      sizes from 50 to 100 were considered more suitable.

PMID- 16813342
TI  - Enumerative and binomial sampling plans for citrus mealybug (Homoptera:
      pseudococcidae) in citrus groves.
AB  - The spatial distribution of the citrus mealybug, Planococcus citri (Risso)
      (Homoptera: Pseudococcidae), was studied in citrus groves in northeastern Spain.
      Constant precision sampling plans were designed for all developmental stages of
      citrus mealybug under the fruit calyx, for late stages on fruit, and for females
      on trunks and main branches; more than 66, 286, and 101 data sets, respectively,
      were collected from nine commercial fields during 1992-1998. Dispersion
      parameters were determined using Taylor's power law, giving aggregated spatial
      patterns for citrus mealybug populations in three locations of the tree sampled.
      A significant relationship between the number of insects per organ and the
      percentage of occupied organs was established using either Wilson and Room's
      binomial model or Kono and Sugino's empirical formula. Constant precision (E =
      0.25) sampling plans (i.e., enumerative plans) for estimating mean densities were
      developed using Green's equation and the two binomial models. For making
      management decisions, enumerative counts may be less labor-intensive than
      binomial sampling. Therefore, we recommend enumerative sampling plans for the use
      in an integrated pest management program in citrus. Required sample sizes for the
      range of population densities near current management thresholds, in the three
      plant locations calyx, fruit, and trunk were 50, 110-330, and 30, respectively.
      Binomial sampling, especially the empirical model, required a higher sample size
      to achieve equivalent levels of precision.

PMID- 16813343
TI  - Transformations of count data for tests of interaction in factorial and split
      plot experiments.
AB  - In applied entomological experiments, when the response is a count-type variable,
      certain transformation remedies such as the square root, logarithm (log), or rank
      transformation are often used to normalize data before analysis of variance. In
      this study, we examine the usefulness of these transformations by reanalyzing
      field-collected data from a split-plot experiment and by performing a more
      comprehensive simulation study of factorial and split-plot experiments. For field
      collected data, significant interactions were dependent upon the type of
      transformation. For the simulation study, Poisson distributed errors were used
      for a 2 by 2 factorial arrangement, in both randomized complete block and split
      plot settings. Various sizes of main effects were induced, and type I error rates
      and powers of the tests for interaction were examined for the raw response
      values, log-, square root-, and rank-transformed responses. The aligned rank
      transformation also was investigated because it has been shown to perform well in
      testing interactions in factorial arrangements. We found that for testing
      interactions, the untransformed response and the aligned rank response performed
      best (preserved nominal type I error rates), whereas the other transformations
      had inflated error rates when main effects were present. No evaluations of the
      tests for main effects or simple effects have been conducted. Potentially these
      transformations will still be necessary when performing these tests.

PMID- 16813344
TI  - Hydroprene prolongs developmental time and increases mortality of Indianmeal moth
      (Lepidoptera: Pyralidae) eggs.
AB  - Eggs of the Indianmeal moth, Plodia interpunctella (Hubner), were exposed to the
      labeled rate of hydroprene (1.9 x 10(-3) mg [AI]/cm2) sprayed on concreted petri
      dishes. These eggs were exposed for 1, 3, 6, 12, and 18 h and until hatching
      (continuous exposure) at temperatures of 16, 20, 24, 28, and 32 degrees C and 57%
      RH until the emergence of first instars. The developmental time and egg mortality
      were significantly influenced by temperature and exposure periods. At 16 degrees
      C, hydroprene did not cause differences in developmental time when eggs were
      exposed for different periods. At temperatures >16 degrees C, both exposure
      period and temperature influenced developmental time. The maximum developmental
      time (15.0 +/- 0.2 d) occurred at 16 degrees C, and the minimum developmental
      time (3.2 +/- 0.3 d) occurred at 32 degrees C. Mortality increased when eggs were
      exposed to hydroprene for longer periods at all of the five tested temperatures.
      The greatest mortality (81.6 +/- 2.1%) occurred when eggs were continuously
      exposed on treated surfaces at 32 degrees C. We used developmental time instead
      of rate (1/ developmental time) to fit simple linear or polynomial regression
      models to the development data. Appropriate models for developmental time and
      mortality were chosen based upon lack-of-fit tests. The regression models can be
      used in predictive simulation models for the population dynamics of Indianmeal
      moth to aid in optimizing use of hydroprene for insect management.

PMID- 16813345
TI  - Effect of temperature, exposure interval, and depth of diatomaceous earth
      treatment on distribution, mortality, and progeny production of lesser grain
      borer (Coleoptera: Bostrichidae) in stored wheat.
AB  - Diatomaceous earth (DE) can be used as a surface treatment in stored wheat
      Triticum aestivum (L.) to control pest infestations. However, it is not known how
      the thickness of the DE-treated wheat layer or grain temperature impact
      effectiveness. Therefore, we conducted an experiment in growth chambers to assess
      the effect of different surface layers of hard winter wheat combined with DE on
      spatial distribution, adult survival, and progeny production of lesser grain
      borer, Rhyzopertha dominica (F.), and to determine whether temperature and
      exposure interval modified this effect. When adult lesser grain borers were
      released in experimental towers containing untreated wheat or wheat admixed with
      DE to a surface layer depth of 15.2, 22.9, or 30.5 cm, they were able to
      penetrate all DE layers and oviposit in the untreated wheat below. However,
      survival was significantly reduced in adults exposed to DE. Survival decreased
      both with increasing depth of the DE-treated wheat and with exposure interval.
      Temperature had no effect on adult survival, but significantly more progeny were
      produced at 32 than at 27 degrees C. Progeny production was inversely correlated
      with the depth of the DE-treated layer. Vertical distribution patterns of
      parental beetles were not significantly different among treatments or exposure
      intervals; however, more insects were found at greater depths at 32 than at 27
      degrees C. The F1 production was reduced by 22% at the thickest DE-treated layer.
      However, we conclude that this level of survival could leave a residual
      population of lesser grain borers that would probably be above an allowable
      threshold for insect damage.

PMID- 16813346
TI  - Studies on the effectiveness of coroplast sticky traps for sampling stable flies
      (Diptera: Muscidae), including a comparison to Alsynite.
AB  - Stable flies, Stomoxys calcitrans (L.) (Diptera: Muscidae), are a blood-feeding
      pest of cattle worldwide. A new trapping material, Coroplast, was compared with
      Alsynite sticky traps based on the number, sex, and parity of stable flies
      caught. Coroplast sticky traps caught more stable flies than Alsynite (trap
      catches of 2384 versus 753 on 15 traps), with this increase attributed to
      catching more males (1531 versus 532) and nulliparous females (817 versus 175);
      parous catches were similar (36 versus 46). The spectral reflectance of Alsynite
      and Coroplast sticky traps is reported. We also examine Coroplast traps in detail
      with respect to trap color. Although clean sheets of Alsynite had a higher solar
      reflectance than Coroplast (90 versus 82% at 450 nm), Coroplast with debris had a
      higher reflectance than debris-covered Alsynite (62 versus 30% at 450 nm). White
      Coroplast was most effective, followed by closely by gray. Black and blue were
      the least effective trapping colors.

PMID- 16813347
TI  - Michigan health system launches integrated campaign using patient testimonials.
AB  - Spectrum Health System in Michigan recently launched The Right Decision campaign,
      which totes the system's heart center and cancer facilities. The effort is
      underway with aggressive print ads, television and radio spots, and Web site
      promotion. The 1,000-bed, acute-care system hopes to raise awareness of the heart
      and cancer centers through real-life patient testimonials.

PMID- 16813348
TI  - GE Healthcare launches multiphase advertising effort.
AB  - GE Healthcare has launched a multi-phase marketing campaign aimed at promoting
      the technological breakthroughs and state-of-the-art equipment that it provides
      hospitals and health systems to ensure that patients are given the best care
      possible. The campaign boasts four new commercials and an interactive Web site
      designed to illustrate healthy living on a global scale.

PMID- 16813349
TI  - Kids are different.
AB  - Medical University of South Carolina Children's Hospital is embarking on a
      campaign called Kids Are Different that targets the state's parents and
      caregivers. The effort promotes the entire facility and positions the hospital as
      the most comprehensive center in South Carolina that is also home to the region's
      only intensive neonatal unit. Television spots and print and billboard ads are
      currently running. The promotion is slated to run through the end of the year.

PMID- 16813350
TI  - Why fair tests are needed: a brief history.

PMID- 16813351
TI  - Review: self-monitoring increases the efficacy and safety of anticoagulant
      therapy.

PMID- 16813352
TI  - Lowering homocysteine with folic acid and B vitamins did not prevent vascular
      events in vascular disease.

PMID- 16813353
TI  - Lowering homocysteine with folic acid and B vitamins did not prevent vascular
      events after myocardial infarction.

PMID- 16813354
TI  - Calcium plus vitamin D did not prevent hip fracture or colorectal cancer in
      postmenopausal women.

PMID- 16813355
TI  - A low-fat dietary pattern intervention did not reduce incidence of breast cancer,
      colorectal cancer, or CVD in postmenopausal women.

PMID- 16813357
TI  - Review: low-molecular-weight heparin is more effective than unfractionated
      heparin for preventing reinfarction in STEMI.

PMID- 16813356
TI  - Abciximab reduced death, MI, and urgent target vessel revascularization in non-ST
      segment elevation acute coronary syndromes.

PMID- 16813358
TI  - Review: strong evidence supports perioperative practices to reduce complications
      from hip fracture.

PMID- 16813359
TI  - Disease-free survival was greater with letrozole than tamoxifen in postmenopausal
      women with early breast cancer.

PMID- 16813360
TI  - Saw palmetto did not differ from placebo for benign prostatic hyperplasia in men.

PMID- 16813361
TI  - Maintenance treatment with paroxetine, but not psychotherapy, prevented recurrent
      major depression in older persons.

PMID- 16813362
TI  - Review: sedative-hypnotics increase adverse effects more than they improve sleep
      quality in older persons with insomnia.

PMID- 16813363
TI  - Lumbar epidural corticosteroid injections provided only short-term relief of
      symptoms and pain in unilateral sciatica.

PMID- 16813364
TI  - Yoga improved function and reduced symptoms of chronic low-back pain more than a
      self-care book.

PMID- 16813365
TI  - Glucosamine and chondroitin sulfate did not improve pain in osteoarthritis of the
      knee.

PMID- 16813366
TI  - Entecavir was more effective than lamivudine in HbeAg-positive chronic hepatitis
      B.

PMID- 16813367
TI  - Benazepril was effective and safe for advanced chronic kidney disease without
      diabetes.

PMID- 16813368
TI  - Review: horse chestnut seed extract is effective for symptoms of chronic venous
      insufficiency.

PMID- 16813369
TI  - Review: MRI is more sensitive but less specific than ultrasonography or spiral CT
      for diagnosis of hepatocellular carcinoma.

PMID- 16813370
TI  - Review: electrocardiography, BNP, and N terminal-pro BNP are more sensitive than
      specific for chronic left ventricular systolic dysfunction.

PMID- 16813371
TI  - Risks for myocardial infarction or nonstroke vascular death after ischemic stroke
      or transient ischemic attack were each 2% per year.

PMID- 16813373
TI  - The revised Geneva score predicted pulmonary embolism in patients with shortness
      of breath or chest pain.

PMID- 16813372
TI  - Review: the Wells clinical prediction guide and D-dimer testing predict deep
      venous thrombosis.

PMID- 16813374
TI  - Assembly of a heterometallic polynuclear Sn(IV)-Cu(I) cluster based on Sn(edt)2
      (edt = ethane-1,2-dithiolate) as a metalloligand.
AB  - Reaction of [Cu(PPh3)2(MeCN)2]ClO4 (1) and Sn(edt)2 (edt = ethane-1,2-dithiolate)
      in dichloromethane afforded a novel compound [Sn3Cu4(S2C2H4)6(mu3
      O)(PPh3)4](ClO4)2 x 3 CH2Cl2 (2), which is the first example of the heptanuclear
      Sn(IV)-Cu(I) oxosulfur complex with a bottle-shaped cluster core. Complex 2 gives
      a blue-green luminescent emission in the solid state. Crystallographic data for
      2: C87H90Cl8Cu4O9P4S12Sn3, trigonal, space group R3, M = 2682.02, a = 18.156(2)
      A, b = 18.156(2) A, c = 54.495(10) A, gamma = 120 degrees, V = 15558(4) A3, Z = 6
      (T = 130.15 K).

PMID- 16813376
TI  - Photoinitiated electron collection at a metal in a rhodium-centered mixed-metal
      supramolecular complex.
AB  - A mixed-metal supramolecular complex [{(bpy)2Ru(dpp)}2RhCl2]5+ has been studied
      and shown to undergo photoinitiated electron collection at the metal center.
      Reported herein is an analysis of the photochemical properties of this complex,
      illustrating the ability of this complex to photoreduce by two electrons by
      converting Rh(III) to Rh(I) and with the trimetallic assembly remaining intact.
      Emission-quenching experiments demonstrate efficient quenching of the Ru --> dpp
      charge-transfer state by the Rh center and the electron-donor dimethylaniline.

PMID- 16813375
TI  - O2 chemistry of dicopper complexes with alkyltriamine ligands. Comparing
      synergistic effects on O2 binding.
AB  - Two dicopper(I) complexes containing tertiary N-methylated hexaaza ligands which
      impose different steric constraints to the Cu ions have been synthesized, and
      their reactivity toward O2 has been compared with a mononuclear related system,
      highlighting the importance of cooperative effects between the metal centers in
      O2 activation.

PMID- 16813377
TI  - Destruction of noncentrosymmetry through chalcogenide salt inclusion.
AB  - A salt-inclusion samarium selenogermanate compound, NaSmGeSe4 x 0.25 Na2Se was
      isolated from a reaction of Na2Se, Sm, GeSe2, and Se. The new structure consists
      of isolated GeSe4 units and bicapped trigonal-prismatic SmSe8, which are linked
      together to form corrugated anionic layers. The topology of the layer is similar
      to the well-known layered compounds ALnQE4 (A = K, Rb, Cs; Ln = lanthanide ions;
      Q = Si, Ge; E = S, Se) with some subtle differences. A selenide anion and Na
      cations in the interlayer space form interesting structures where Se-centered
      trigonal-prismatic polyhedra of SeNa6 are edge-shared and pass through a twofold
      rotation axis. Hence, this compound crystallizes in a centrosymmetric space group
      in contrast to the noncentrosymmetric structures adopted by the ALnQE4 series of
      compounds. Raman and diffuse-reflectance spectra were also analyzed for the title
      compound.

PMID- 16813378
TI  - Heptametallic bowl-shaped complexes derived from conjugated Schiff-base
      macrocycles: synthesis, characterization, and X-ray crystal structures.
AB  - The reaction of chelating conjugated macrocycles 1a-c with Zn(OAc)2 gives bowl
      shaped heptanuclear Zn complexes featuring Zn in tetrahedral, octahedral, and
      square-pyramidal geometries. Crystallographic and NMR results indicate that
      vacant Zn coordination sites within the bowl may be accessed, suggesting that
      these coordination complexes may be used as mimics for Zn fingers and carbonic
      anhydrase.

PMID- 16813379
TI  - An S = 2 cyanide-bridged trinuclear Fe(III)2Ni(II) single-molecule magnet.
AB  - Treatment of [NEt4][(pzTp)Fe(III)(CN)3] (1) with Ni(II)(OTf)2 (OTf =
      trifluoromethanesulfonate) and 1,5,8,12-tetraazadodecane (L) affords
      {[(pzTp)Fe(III)(CN)3]2[Ni(II)L]} x 1/2MeOH (2), while 2,2'-bipyridine (bipy)
      affords {[(pzTp)Fe(III)(CN)3]2[Ni(II)(bipy)2]} x 2 H2O (3). Magnetic measurements
      indicate that 2 and 3 have S = 2 ground states and that 3 exhibits slow
      relaxation of the magnetization above 2 K.

PMID- 16813380
TI  - Rational design of new bright luminescent zinc diphosphonates with 12-member ring
      channels.
AB  - Three new zinc diphosphonates possessing bright purple fluorescence, high thermal
      stability, and an intriguing 3D pillared open framework with 1D 12-member ring
      channels encapsulating luminescent guest have been rationally designed and
      synthesized by introducing a luminescent guest as a structure-directing agent.

PMID- 16813381
TI  - Self-assembly of a luminescent zinc(II) complex: a supramolecular host-guest
      fluorescence signaling system for selective nitrobenzene inclusion.
AB  - A luminescent Zn(II) complex, [Zn(bpy)(aba)2] (1) {bpy = 2,2'-bipyridyl and aba =
      4-dimethylaminobenzoate} has been synthesized as a white solid. Complex 1 shows
      unusually high selectivity toward nitrobenzene in the presence of other organic
      guests in solution, as well as in the vapor phase, resulting in both a dramatic
      color change and a concomitant quenching of luminescence. When crystallized from
      nitrobenzene, 1 affords deep red crystals with the composition [Zn(bpy)(aba)2] x
      C6H5NO2 (2) as a hydrogen-bonded channel structure via unusual intermolecular C
      H...C(sp3) and H...H interactions. Inside the channels, nitrobenzene molecules
      form infinite polar linear tapes through strong C-H...O interactions in a head-to
      tail fashion. The desorption and resorption of nitrobenzene can be achieved in a
      thermally reversible manner that can be monitored by X-ray powder diffraction
      patterns.

PMID- 16813383
TI  - Largest discrete supramolecular architecture based on a lanthanide ion:
      [lanthanum(III)18{N,N'-bis(2-pyridylmethyl)-N,N'-1,2-ethanediylbis(D
      alaninate)}18(H2O)36]18+.
AB  - The largest discrete octadecameric architecture based on a lanthanide ion has
      been found in the crystal structure of a La{N,N'-bis(2-pyridylmethyl)-N,N'-1,2
      ethanediylbis(D-alaninate)} complex.

PMID- 16813382
TI  - Sequential generation of one-dimensional networks based on a differentiated
      bischelate-type ligand bearing both 4,5-diazafluorene and dithiolene units.
AB  - A novel dithiolene ligand appended with a 4,5-diazafluorene moiety has been
      synthesized and used for the preparation of discrete nickel and mercury complexes
      and a one-dimensional polymer in the presence of sodium cations.

PMID- 16813384
TI  - Unexpected Pt(II) migration between the calixarene oxygen atoms.
AB  - Reaction between the 1,3-bis(trimethylsilyl) ether of calix[4]arene and
      platinum(II) difluoro complexes unexpectedly results in the formation of the 1,2
      bridging platinum(II) calixarene complex, which, upon treatment with 2 equiv of
      acyl chloride, reinstates the 1,3-disubstitution pattern in the calixarene
      moiety.

PMID- 16813385
TI  - Theoretical probing of deltahedral closo-auroboranes B(x)Au(x)2- (x = 5-12).
AB  - Using density functional theory calculations, here we show that a series of
      B(x)Au(x)2- (x = 5-12) dianions possesses structure and bonding similar to the
      famous deltahedral closo-borane cages, B(x)H(x)2-. Effective atomic charges on Au
      in B(x)Au(x)2- are very similar to those on H in B(x)H(x)2-, indicating that Au
      in the closo-auroboranes is indeed analogous to H in the closo-boranes. The
      present theoretical predictions of B(x)Au(x)2- suggest that the closo-auroborane
      species are viable new chemical building blocks that may be synthesized in bulk.
      The Au atoms in the closo-auroboranes represent highly atomically dispersed Au
      and may potentially exhibit novel catalytic and chemical properties.

PMID- 16813386
TI  - Microwave-assisted synthesis of a hexanuclear Mn(III) single-molecule magnet.
AB  - The use of microwave heating has improved the reaction rate, enhanced the yield
      of an inorganic cluster complex, and allowed for the high-temperature/high
      pressure synthesis of a Mn(III) single-molecule magnet.

PMID- 16813387
TI  - Preparation and structural characterization of transition-metal complexes
      featuring the cymantrenyl(bromo)boryl ligand.
AB  - In the present paper, we describe the first structural characterization of
      cymantrenyl(dihalo)borane and report on its use for the synthesis of novel
      cymantrenylboryl complexes.

PMID- 16813388
TI  - Synthesis, structure, and properties of a dimeric chromium(II) pyrazolato complex
      with a long chromium-chromium distance. Maintenance of a dimeric structure in
      solution and interconversion between dimeric and monomeric structures.
AB  - The synthesis, solid-state structure, and solution structure of Cr2(tBu2pz)4 are
      described. This complex is obtained by sublimation of the monomeric species
      Cr(tBu2pz)2(4-tBupy)2 and contains long chromium-chromium distances that are
      enforced by the divergent nature of the pyrazolato ligands.

PMID- 16813389
TI  - A cube in a tetrahedron: microwave-assisted synthesis of an octametallic Fe(III)
      cluster.
AB  - The microwave-assisted reaction of Fe(O2CMe)2 with salicylaldoxime (saoH2) in
      pyridine produces an octametallic cluster in crystalline form in 2 min. The core
      describes a cube encapsulated in a tetrahedron, while sao2- exhibits a novel
      coordination mode.

PMID- 16813391
TI  - Speciation of the curium(III) ion in aqueous solution: a combined study by
      quantum chemistry and molecular dynamics simulation.
AB  - The structures of aquo complexes of the curium(III) ion have been systematically
      studied using quantum chemical and molecular dynamics (MD) methods. The first
      hydration shell of the Cm3+ ion has been calculated using density functional
      theory (DFT), with and without inclusion of the conductor-like polarizable
      continuum medium (CPCM) model of solvation. The calculated results indicate that
      the primary hydration number of Cm3+ is nine, with a Cm-O bond distance of 2.47
      2.48 A. The calculated bond distances and the hydration number are in excellent
      agreement with available experimental data. The inclusion of a complete second
      hydration shell of Cm3+ has been investigated using both DFT and MD methods. The
      presence of the second hydration shell has significant effects on the primary
      coordination sphere, suggesting that the explicit inclusion of second-shell
      effects is important for understanding the nature of the first shell. The
      calculated results indicate that 21 water molecules can be coordinated in the
      second hydration shell of the Cm3+ ion. MD simulations within the hydrated-ion
      model suggest that the second-shell water molecules exchange with the bulk
      solvent with a lifetime of 161 ps.

PMID- 16813390
TI  - Electronic, magnetic, and structural characterization of the five-coordinate,
      high-spin iron(II) nitrato complex [Fe(TpivPP)(NO3)]-.
AB  - The preparation and characterization of the five-coordinate iron(II) porphyrinate
      derivative [Fe(TpivPP)(NO3)]- (TpivPP = picket-fence porphyrin) is described.
      Structural and magnetic susceptibility data support a high-spin state (S = 2)
      assignment for this species. The anionic axial nitrate ligand is O-bound, through
      a single O atom, with an Fe-O bond length of 2.069(4) A. The planar nitrate
      ligand bisects a N(p)-Fe-N(p) angle. The average Fe-N(p) bond length is 2.070(16)
      A. The Fe atom is located 0.49 A out of the 24-atom mean porphyrin plane toward
      the nitrate ligand. From solid-state Mossbauer data, the isomer shift of 0.98
      mm/s at 77 K is entirely consistent with high-spin iron(II). However the
      quadrupole splitting of 3.59 mm/s at 77 K is unusually high for iron(II), S = 2
      systems but within the range of other five-coordinate high-spin ferrous complexes
      with a single anionic axial ligand. Crystal data for [K(222)][Fe(TpivPP)(NO3)] x
      C6H5Cl: a = 17.888 (5) A, b = 21.500 (10) A, c = 22.514 (11) A, beta = 100.32 (3)
      degrees, monoclinic, space group P2(1)/n, V = 8519 A3, Z = 4.

PMID- 16813392
TI  - Deoligomerization by cocomplexation: syntheses and structures of aluminum-calcium
      alkoxides and aryloxides.
AB  - Reactions of oligomeric "Ca(dbbfo)2" and Ca9(CH3OCH2CH2O)18(CH3OCH2CH2OH)2 with
      Al(CH3)3 in toluene gave tetranuclear heterobimetallic [Ca(mu-dbbfo){(mu
      dbbfo)(mu-CH3)Al(CH3)2}]2 (71%) and polymeric Ca{(mu-CH3OCH2CH2O)(mu
      CH3)Al(CH3)2}2 (86%). The latter can be obtained as monomeric THF adduct Ca{(mu
      CH3OCH2CH2O)Al(CH3)3}2(THF)2 (78%) when a mixture of solvents is used. The
      results, including an initial L-lactide polymerization test, are discussed in the
      context of calcium alkoxo cluster degradation in solution.

PMID- 16813394
TI  - Sensitive and selective PET-based diimidazole luminophore for Zn(II) ions: a
      structure-activity correlation.
AB  - 3-(3-Ethoxymethyl-1H-imidazol-2-yl)-3-(1-ethoxymethyl-1H-imidazol-2-yl)-3H
      benzo[de]isochromen-1-one, 4, is a novel photoinduced electron transfer (PET)
      chemosensor that becomes fluorescent upon binding metal ions and shows a strong
      preference toward Zn(II) ions. The new bisimidazol PET sensor and its zinc
      complex were prepared and characterized in terms of their crystal structures,
      absorption and emission spectra, and orbital energy diagrams. Free 4 is a weakly
      luminescent species. On the basis of detailed DFT calculations, we suggest that
      the poor luminescence yield of free 4 originates from its orbital structure in
      which two pi-orbitals of the two imidazole rings, HOMO and HOMO-1, are situated
      between two pi-orbitals of the isochromene-one system, HOMO-2 and LUMO. The
      absorption and emission processes occur between the two pi-orbitals of the
      isochromene-one system, HOMO-2 and LUMO, and the two pi-imidazole orbitals serve
      as quenchers for the excited state of the molecule through nonradiative
      processes. Upon binding Zn(II) ions, 4 becomes a highly luminescent species
      having a luminescence maximum peaking at 375 nm (lambda(ex) = 329 nm). The
      significant 900-fold enhancement in luminescence upon binding of the Zn(II) ions
      is attributed to the stabilization of the pi-orbitals of the imidazole rings upon
      their engagement in new bonds with the zinc ion. The affinity of 4 to zinc ions
      in acetonitrile is found to be very high, Ka > 3 x 10(6) M(-1), while with other
      metals ions, the association constants are considerably weaker.

PMID- 16813393
TI  - Biomimetic studies on selenoenzymes: modeling the role of proximal histidines in
      thioredoxin reductases.
AB  - The roles of built-in thiol cofactors and the basic histidine (His) residues in
      the active site of mammalian thioredoxin reductases (TrxRs) are described with
      the help of experimental and density functional theory calculations on small
      molecule model compounds. The reduction of selenenyl sulfides by thiols in
      selenoenzymes such as glutathione peroxidase (GPx) and TrxR is crucial for the
      regeneration of the active site. Experimental as well as theoretical studies were
      carried out with model selenenyl sulfides to probe their reactivity toward
      incoming thiols. We have shown that the nucleophilic attack of thiols takes place
      at the selenium center in the selenenyl sulfides. These thiol exchange reactions
      would hamper the regeneration of the active species selenol. Therefore, the basic
      His residues are expected to play crucial roles in the selenenyl sulfide state of
      TrxR. Our model study with internal amino groups in the selenenyl sulfide state
      reveals that the basic His residues may play important roles by deprotonating the
      thiol moiety in the selenenic acid state and by interacting with the sulfur atom
      in the selenenyl sulfide state to facilitate the nucleophilic attack of thiol at
      sulfur rather than at selenium, thereby generating the catalytically active
      species selenol. This model study also suggests that the enzyme may use the
      internal cysteines as cofactors to overcome the thiol exchange reactions.

PMID- 16813395
TI  - On the structure and spin states of Fe(III)-EDDHA complexes.
AB  - DFT methods are suitable for predicting both the geometries and spin states of
      EDDHA-Fe(III) complexes. Thus, extensive DFT computational studies have shown
      that the racemic-Fe(III) EDDHA complex is more stable than the meso isomer,
      regardless of the spin state of the central iron atom. A comparison of the energy
      values obtained for the complexes under study has also shown that high-spin (S =
      5/2) complexes are more stable than low-spin (S = 1/2) ones. These computational
      results matched the experimental results of the magnetic susceptibility values of
      both isomers. In both cases, their behavior has been fitted as being due to
      isolated high-spin Fe(III) in a distorted octahedral environment. The study of
      the correlation diagram also confirms the high-spin iron in complex 2b. The
      geometry optimization of these complexes performed with the standard 3-21G* basis
      set for hydrogen, carbon, oxygen, and nitrogen and the Hay-Wadt small-core
      effective core potential (ECP) including a double-xi valence basis set for iron,
      followed by single-point energy refinement with the 6-31G* basis set, is suitable
      for predicting both the geometries and the spin-states of EDDHA-Fe(III)
      complexes. The presence of a high-spin iron in Fe(III)-EDDHA complexes could be
      the key to understanding their lack of reactivity in electron-transfer processes,
      either chemically or electrochemically induced, and their resistance to
      photodegradation.

PMID- 16813396
TI  - Synthesis, structural characterization, experimental, and computational
      spectrophotometric studies of 8-quinolinyloxymethyphosphonate compounds.
AB  - The synthesis of diethyl-8-quinolinyloxymethylphosphonate 1 and 8
      quinolinyloxymethylphosphonic acid hemihydroiodide 2 is reported along with their
      spectroscopic and analytical characteristics (NMR, infrared, mass spectra, and
      elemental analysis). The single-crystal X-ray structure of 2 is described.
      Solutions of the disodium phosphonate 3, from 2 and sodium hydroxide, were
      prepared and used in situ. The coordination complex between 1 and zinc chloride 4
      is described according to its single-crystal X-ray structure. The
      spectrophotometric features (absorption and emission) of 1, 2, 3, and 4 are
      reported along with the fluorescence response and affinity of 3 to some metal
      cations. The origin of the fluorescence from compounds 1 and 4 is investigated
      using density functional theory and the oscillator strength for each transition
      is computed. Two deactivation pathways, one of which is only weakly emissive, are
      identified in 4. In contrast to 4, which is only moderately more emissive than 1
      a strong zinc-activated fluorescence response is observed from aqueous solutions
      of 3.

PMID- 16813397
TI  - Synthesis, structure, and magnetic properties of (6-9)-nuclear Ni(II)
      trimethylacetates and their heterospin complexes with nitroxides.
AB  - New polynuclear nickel trimethylacetates [Ni6(OH)4(C5H9O2)8(C5H10O2)4] (6),
      [Ni7(OH)7(C5H9O2)7(C5H10O2)6(H2O)] x 0.5 C6H14 x 0.5 H2O (7),
      [Ni8(OH)4(H2O)2(C5H9O2)12] (8), and [Ni9(OH)6(C5H9O2)12(C5H10O2)4] x C5H10O2 x 3
      H2O (9), where C5H9O2 is trimethylacetate and C5H10O2 is trimethylacetic acid,
      have been found. Their structures were determined by X-ray crystallography.
      Because of their high solubility in low-polarity organic solvents, compounds 6-9
      reacted with stable organic radicals to form the first heterospin compounds based
      on polynuclear Ni(II) trimethylacetate and nitronyl nitroxides containing
      pyrazole (L(1)-L(3)), methyl (L(4)), or imidazole (L(5)) substituent groups,
      respectively, in side chain [Ni7(OH)5(C5H9O2)9(C5H10O2)2(L(1))2(H2O)] x 0.5 C6H14
      x H2O (6+1a), [Ni7(OH)5(C5H9O2)9(C5H10O2)2(L2)2(H2O)] x H2O (6+1b),
      [Ni7(OH)5(C5H9O2)9(C5H10O2)2(L(3))2(H2O)] x H2O (6+1c),
      [Ni6(OH)3(C5H9O2)9(C5H10O2)4(L(4))] x 1.5 C6H14 (6''), and
      [Ni4OH)3(C5H9O2)5(C5H10O2)4(L(5))] x 1.5 C7H8 (4). Their structures were also
      determined by X-ray crystallography. Although Ni(II) trimethylacetates may have
      varying nuclearity and can change their nuclearity during recrystallization or
      interactions with nitroxides, this family of compounds is easy to study because
      of its topological relationship. For any of these complexes, the polynuclear
      framework may be derived from the [Ni6] polynuclear fragment {Ni6(mu4-OH)2(mu3
      OH)2(mu2-C5H9O2-O,O')6(mu2-C5H9O2-O,O)(mu4-C5H9O2-O,O,O',O')(C5H10O2)4}, which is
      shaped like an open book. On the basis of this fragment, the structure of 7
      nuclear compounds (7 and 6+1a-c) is conveniently represented as the result of
      symmetric addition of other mononuclear fragments to the four Ni(II) ions lying
      at the vertexes of the [Ni6] open book. The 9-nuclear complex is formed by the
      addition of trinuclear fragments to two Ni(II) ions lying on one of the lateral
      edges of the [Ni6] open book. This wing of the 9-nuclear complex preserves its
      structure in another type of 6-nuclear complex (6'') with the boat configuration.
      If, however, two edge-sharing Ni(II) ions are removed from [Ni6] (one of these
      lies at a vertex of the open book and the other, on the book-cover line), we
      obtain a 4-nuclear fragment recorded in the molecular structure of 4. Twinning of
      this 4-nuclear fragment forms highly symmetric molecule 8, which is a new
      chemical version of cubane.

PMID- 16813398
TI  - Kinetics, mechanism, and computational studies of rhenium-catalyzed
      desulfurization reactions of thiiranes (thioepoxides).
AB  - The oxorhenium(V) dimer {MeReO(edt)}2 (1; where edt = 1,2-ethanedithiolate)
      catalyzes S atom transfer from thiiranes to triarylphosphines and triarylarsines.
      Despite the fact that phosphines are more nucleophilic than arsines, phosphines
      are less effective because they rapidly convert the dimer catalyst to the much
      less reactive catalyst [MeReO(edt)(PAr3)] (2). With AsAr3, which does not yield
      the monomer, the rate law is given by v = k[thiirane][1], independent of the
      arsine concentration. The values of k at 25.0 degrees C in CDCl3 are 5.58 +/-
      0.08 L mol(-1) s(-1) for cyclohexene sulfide and ca. 2 L mol(-1) s(-1) for
      propylene sulfide. The activation parameters for cyclohexene sulfide are
      deltaH(double dagger) = 10.0 +/- 0.9 kcal mol(-1) and deltaS(double dagger) = -21
      +/- 3 cal K(-1) mol(-1). Arsine enters the catalytic cycle after the rate
      controlling release of alkene, undergoing a reaction with the Re(VII)(O)(S)
      intermediate that is so rapid in comparison that it cannot be studied directly.
      The use of a kinetic competition method provided relative rate constants and a
      Hammett reaction constant, rho = -1.0. Computations showed that there is little
      thermodynamic selectivity for arsine attack at O or S of the intermediate. There
      is, however, a large kinetic selectivity in favor of Ar3AsS formation: the
      calculated values of deltaH(double dagger) for attack of AsAr3 at Re=O vs Re=S in
      Re(VII)(O)(S) are 23.2 and 1.1 kcal mol(-1), respectively.

PMID- 16813399
TI  - Structurally complex cobalt intermetallics grown from liquid aluminum:
      Co19Al45Si(10-x) (x = 0.13) and Co5Al14Si2.
AB  - The cobalt aluminum silicides Co19Al45Si(10-x) (x = 0.13) and Co5Al14Si2 were
      synthesized in liquid aluminum and characterized by single-crystal X-ray
      diffraction. Co19Al45Si(10-x) (x = 0.13) crystallizes in the monoclinic space
      group C2/c with lattice parameters a = 19.991(2) A, b = 19.143(2) A, c =
      12.8137(15) A, beta = 123.583(2) degrees. Co5Al14Si2 adopts the orthorhombic
      space group Pnma with cell parameters a = 13.8948(19) A, b = 23.039(3) A, c =
      7.3397(10) A. Both structures are exceptionally complex with the Co2Si2 rhombus
      being a common building motif. The coordination environments of cobalt atoms
      resemble those of the transition metals in typical quasi-crystal approximants.
      Co5Al14Si2 shows oxidation resistance in air up to 1000 degrees C by forming a
      dense-packed Al2O3 layer on the surface of the crystal.

PMID- 16813400
TI  - Supramolecular architectures and magnetic properties of coordination polymers
      based on pyrazinedicarboxylato ligands showing embedded water clusters.
AB  - The synthesis, crystal structure, and magnetic behavior of nine transition-metal
      complexes based on pyrazine-2,5-dicarboxylato (pz25dc) and pyrazine-2,3
      dicarboxylato (pz23dc) ligands are reported. The pz25dc ligand displays a bis
      bidentate coordination mode, with the carboxylate groups almost coplanar with the
      pyrazine ring, to afford polymeric 1-D chains [Mn(1), Fe(2), Zn(3), and Cu(4 and
      5)] and discrete dimeric entities [Mn(6)] when the 1,10-phenanthroline (phen)
      blocking ligand is used to avoid further polymerization. The nonplanar pz23dc
      ligand chelates to a unique copper center, while it bridges another one or two
      metal centers via the remaining carboxylate group, leading to 1-D polymeric
      chains (7), ladder chains (8), and sheets (9). The crystal packing of the metal
      organic frameworks of compounds 4-9 generates voids which are occupied by
      assembled water molecules. The different water cluster patterns (tapes, four
      membered discrete rings, and chains for compounds 6, 8, and 9, respectively) and
      their role in the cohesiveness of supramolecular architectures are analyzed.
      Thermogravimetric and variable-temperature X-ray powder diffraction studies have
      revealed the occurrence of reversible dehydration processes in compounds 6, 8,
      and 9. Furthermore, the magnetic behavior of these compounds has been studied in
      order to analyze the capability of the pyrazine ring to transmit magnetic
      interactions.

PMID- 16813401
TI  - Coordination capabilities of a novel organic polychlorotriphenylmethyl
      monosulfonate radical.
AB  - The treatment of alpha-H-p-H-PTM (PTM = polychlorotriphenylmethane) with oleum
      65% followed by deprotonation and oxidation leads to the isolation of a novel
      pure organic radical PTMSO3H x 3 H2O x 0.5 hexane (2). The X-ray diffraction of 2
      reveals a layered structure with disordered H2O molecules between facing sulfonic
      acid groups. We have explored the coordination abilities of the sulfonate
      derivative using different metals. The treatment of 2 with mild bases yields the
      sulfonate radical PTMSO3Na x H2O (3). On the other hand, the new compound
      [Cu(py)2(H2O)4](PTMSO3)2 x 2 H2O x 2 EtOH (4) has been crystallized using Cu(II)
      as the metallic counterion in the presence of pyridine. The structure reveals a
      solvent-separated ion-pair-type compound, with no direct coordination of the
      metal ion with the sulfonate group, and the formation of organic layers between
      layers of transition metal complexes. This situation has been overcome by
      favoring the stabilization of the sulfonate group over the Cu(II) center by
      changing the pyridine ligand to cyclam. This has led to compound
      [Cu(cyclam)](PTMSO3)2 x 6 EtOH (5a), in which the sulfonate group acts as a
      monodentate axial ligand for the Cu(II) center. We have observed a single-to
      single crystal rearrangement from 5a to [Cu(cyclam)](PTMSO3)2 (5b) because of the
      loss of the solvent of crystallization, without significant modification of the
      metal coordination environment. All species have been structurally and
      magnetically characterized, and the magnetic coupling between the organic
      radicals and the metal paramagnetic centers is discussed.

PMID- 16813402
TI  - Two new hybrid organic/inorganic copper(II)-oxovanadate(V) diphosphonates:
      [Cu2(phen)2(O3PCH2PO3)(V2O5)(H2O)] x H2O and [Cu2(phen)2(O3P(CH2)3PO3)(V2O5)] x
      C3H8. Synthesis, structure, and magnetic properties.
AB  - Two new hybrid organic/inorganic copper oxovanadium diphosphonates
      [Cu2(phen)2(O3PCH2PO3)(V2O5)(H2O)] x H2O (1) and
      [(Cu2(phen)2(O3P(CH2)3PO3)(V2O5)] x C3H8 (2) have been obtained by hydrothermal
      synthesis. The compounds are monoclinic, and they crystallize in the space group
      P2(1)/n with cell parameters of a = 11.788(2) A, b = 17.887(3) A, c = 14.158(2)
      A, and beta = 93.99(0) degrees and in the space group C2/c with cell parameters
      of a = 11.025(1) A, b = 18.664(2) A, c = 15.054(2) A, and beta = 90.06(0)
      degrees, respectively. Both compounds present two-dimensional frameworks built up
      from infinite chains of corner-sharing vanadium tetrahedra and diphosphonate
      groups connected by copper tetramers for (1) and copper dimers for (2). The
      remarkable feature of (2) is the encapsulation of propane molecules, stabilized
      by strong hydrogen bonding between the layers. The magnetic properties of the
      compounds have been investigated showing antiferromagnetic coupling with Tmax =
      64 K for (1) and Curie-like paramagnetic behavior for (2).

PMID- 16813403
TI  - Synthesis, crystal structure, and porosity estimation of hydrated erbium
      terephthalate coordination polymers.
AB  - The reaction of the Er3+ ion with polycarboxylate ligands in gel media leads to
      coordination polymers exhibiting various structural types and dimensionalities.
      Five Er3+/1,4-benzenedicarboxylate-based coordination polymers have been obtained
      in such conditions. Four out of the five are new. Their crystal structures are
      reported and compared herein. Compound 1, namely, Er2Ter3(H2O)6, where H2Ter
      symbolizes the terephthalic acid, crystallizes in the space group P1 (No. 2) with
      a = 7.8373(10) A, b = 9.5854(2) A, c = 10.6931(2) A, alpha = 68.7770(8) degrees,
      beta = 70.8710(8) degrees, and gamma = 75.3330(12) degrees. It has already been
      reported elsewhere. The last four compounds are new. Compound 2, namely,
      Er2Ter3(H2O)6 x 2 H2O, crystallizes in the space group P121/a1 (No. 14) with a =
      6.7429(2) A, b = 22.4913(7) A, c = 9.6575(3) A, and beta = 91.6400(18) degrees.
      Compound 3, namely Er2Ter3(H2O)8 x 2 H2O crystallizes in the space group P1 (No.
      2) with a = 7.5391(2) A, b = 10.0533(3) A, c = 10.4578(3) A, alpha = 87.7870(10)
      degrees, beta = 82.5510(11) degrees, and gamma = 86.2800(16) degrees. Compound 4,
      namely, Er2Ter3(H2O)6 x 2 H2O crystallizes in the space group C2/c (No. 15) with
      a = 38.5123(13) A, b = 11.1241(4) A, c = 7.0122(2) A, and beta = 98.634(2)
      degrees. Compound 5, namely, Er2Ter3(H2O)6 x H2O, crystallizes in the space group
      P1 (No. 2) with a = 6.8776(10) A, b = 11.0420(2) A, c = 18.5675(3) A, alpha =
      84.7240(6) degrees, beta = 81.8380(6) degrees, and gamma = 84.1770(8) degrees. A
      computational method has also been developed to evaluate the potential porosity
      of the coordination polymers. This method is described and then applied to the
      different Er2Ter3(H2O)n coordination polymers previously described.

PMID- 16813404
TI  - Lone-pair activity in lead(II) complexes with unsymmetrical lariat ethers.
AB  - We have carried out a study about the structural effect of the lone-pair activity
      in lead(II) complexes with the unsymmetrical lariat ethers L(7), L(8), (L(8)-H)-,
      (L(9)-H)-, and (L(10)-H)-. All these ligands are octadentate and differ by the
      aromatic unit present in their backbones: pyridine, phenol, phenolate,
      thiophenolate, and pyrrolate, respectively. In these lead(II) complexes, the
      receptor may adopt two possible syn conformations, depending on the disposition
      of the pendant arms over the crown moiety fragment. The conformation where the
      pendant arm holding the imine group is placed above the macrocyclic chain
      containing two ether oxygen atoms has been denoted as I, whereas the term II
      refers to the conformation in which such pendant arm is placed above the
      macrocyclic chain containing the single oxygen atom. Compounds of formula
      [Pb(L(7))](ClO4)2 (1) and [Pb(L(8)-H)](ClO4) (2) were isolated and structurally
      characterized by X-ray diffraction analyses. The crystal structure of 1 adopts
      conformation I and shows the lead(II) ion bound to the eight available donor
      atoms of the bibracchial lariat ether in a holodirected geometry, whereas the
      geometry of 2 is best described as hemidirected, with the receptor adopting
      conformation II. The five systems [Pb(L(7))]2+, [Pb(L(8))]2+, [Pb(L(8)-H)]+,
      [Pb(L(9)-H)]+, and [Pb(L(10)-H)]+ were characterized by means of density
      functional theory calculations (DFT) performed by using the B3LYP model. An
      analysis of the natural bond orbitals (NBOs) indicates that the Pb(II) lone-pair
      orbital remains almost entirely s in character in the [Pb(L(7))]2+ complexes,
      whereas in [Pb(L(8)-H)]+, the Pb(II) lone pair is polarized by a certain 6p
      contribution. The reasons for the different roles of the Pb(II) lone pair in
      compounds 1 and 2 as well as in the related model compounds are discussed. Our
      results point to the presence of a charged donor atom in the ligand (such as a
      phenolate oxygen atom, pyrrolate nitrogen atom, or even thiophenolate sulfur
      atom) favoring hemidirected geometries.

PMID- 16813405
TI  - Models of the cytochromes: crystal structures and EPR spectral characterization
      of low-spin bis-imidazole complexes of (OETPP)Fe(III) having intermediate ligand
      plane dihedral angles.
AB  - The preparation, EPR spectra, and crystal structures of
      octaethyltetraphenylporphyrinatoiron(III) having two imidazole, N
      benzylimidazole, and N-methylimidazole axial ligands are reported,
      [(OETPP)Fe(HIm)2]Cl, [(OETPP)Fe(N-BzIm)2]Cl, and [(OETPP)Fe(N-MeIm)2]Cl. Despite
      large variation in axial ligand size, the unit cell parameters for all complexes
      are very similar; each structure has the same basic motif, with large voids
      formed by the extended porphyrin framework (filled by ordered or disordered axial
      ligands and disordered solvent), which allows differently sized ligands to fit
      within the same cell dimensions. Each porphyrin core adopts a saddled
      conformation with absolute value(deltaC(beta)) = 1.13-1.15 A. The dihedral angles
      between axial ligand planes, delta phi, are far from being either ideal parallel
      or perpendicular: 30.1 degrees, 57.2 degrees for [(OETPP)Fe(HIm)2]Cl (molecules 1
      and 2), 56.8 degrees for [(OETPP)Fe(N-BzIm)(2)]Cl, and 16.0 degrees, 44.6
      degrees, 59.6 degrees, and 88.1 degrees for [(OETPP)Fe(N-MeIm)2]Cl, which has
      disordered axial ligands. Among the complexes of this study, an axial ligand
      delta phi of 56.8 degrees is found to be the largest "parallel" angle (as defined
      by the observation of a normal rhombic or Type II EPR signal (N-BzIm, g = 3.08,
      2.19, 1.31)), while 57.2 degrees is found to be the smallest "perpendicular"
      delta phi (as defined by the observation of a "large gmax" or Type I EPR signal
      (HIm, gmax = 3.24)). From the results of this study, it is clear that the size of
      the largest g for Types I and II complexes varies continuously, with no break
      between the two. While the switch in EPR signal type, from Type II to Type I,
      appears to be very sharp in this study, this may be somewhat artificial based
      upon limited numbers of examples and the required saddle distortion of the
      (OETPP)Fe(III) complexes. However, in comparison to several proteins with
      dihedral angles near 60 degrees and Type II EPR spectra, we may conclude that the
      switch in EPR signal type occurs near 57 degrees +/- 3-5 degrees.

PMID- 16813406
TI  - Syntheses and characterization of oxygen/sulfur-bridged incomplete cubane-type
      clusters, [Mo3S4Tp3]+ and [Mo3OS3Tp3]+, and a mixed-metal cubane-type cluster,
      [Mo3FeS4ClTp3]. X-ray structures of [Mo3S4Tp3]Cl, [Mo3OS3Tp3]PF6, and
      [Mo3FeS4ClTp3].
AB  - The reaction of [Mo3S4(H2O)9]4+ (1) with hydrotris(pyrazolyl)borate (Tp) ligands
      produced [Mo3S4Tp3]Cl x 4 H2O ([3]Cl x 4 H2O) in an excellent yield. An X-ray
      structure analysis of [3]Cl x 4 H2O revealed that each molybdenum atom bonded to
      the Tp ligand. We report four salts of 3, [3]Cl x 4 H2O, [3]tof x 2 H2O, [3]PF6 x
      H2O, and [3]BF4 x 2 H2O in this paper. The solubility and stability of the
      chloride salt in organic solvents differ completely from those of the other
      salts. We have also prepared a new compound, [Mo3OS3Tp3]PF6 x H2O ([4]PF6 x H2O),
      via the reaction of [Mo3OS3(H2O)9]4+ (2) with KTp in the presence of NH4PF6. All
      the molybdenum atoms bonded to Tp ligand. 1H NMR signals corresponding to nine
      protons bonded to three pyrazole rings in one Tp were observed in a spectrum (at
      253 K) of [3]BF4 x 2 H2O. It shows that cluster 3 has a 3-fold rotation axis in
      CD2Cl2 solution. Twenty-one 1H NMR signals corresponding to twenty-seven protons
      bonded to nine pyrazole rings in three Tp ligands were observed in a spectrum (at
      233 K) of [4]PF6 x H2O; obviously, 4 has no 3-fold rotation axis, in contrast to
      3. The short CH...mu3S distance caused large upfield chemical shifts in the 1H
      NMR spectra of 3 and 4. The reaction of 3 with metallic iron in CH2Cl2 produced
      [Mo3FeS4XTp3] (X = Cl (5), Br (6)). X-ray structure analysis of 5 has revealed
      the existence of a cubane-type core Mo3FeS4. Complex 3 functions as a metal
      complex ligand for preparing a novel mixed-metal complex even in nonaqueous
      solvents. The cyclic voltammogram of 5 shows two reversible one-electron couples
      (E(1/2) = -1.40 and 0.52 V vs SCE) and two irreversible one-electron oxidation
      processes (E(pc) = 1.54 and 1.66 V vs SCE).

PMID- 16813407
TI  - Mechanistic studies of the oxidative N-dealkylation of a substrate tethered to
      carboxylate-bridged diiron(II) complexes, [Fe2(mu-O2CAr(Tol))2(O2CAr(Tol))2(N,N
      Bn2en)2].
AB  - Carboxylate-bridged diiron(II) centers activate dioxygen for the selective
      oxidation of hydrocarbon substrates in bacterial multicomponent monooxygenases.
      Synthetic analogues of these systems exist in which substrate fragments tethered
      to the diiron(II) core through attachment to an N-donor ligand are oxidized by
      transient species that arise following the introduction of O2 into the system.
      The present study describes the results of experiments designed to probe
      mechanistic details of these oxidative N-dealkylation reactions. A series of
      diiron(II) complexes with ligands N,N-(4-R-Bn)Bnen, where en is ethylenediamine,
      Bn is benzyl, and R-Bn is benzyl with a para-directing group R = Cl, F, CH3, t
      Bu, or OCH3, were prepared. A Hammett plot of the oxygenation product
      distributions of these complexes, determined by gas chromatographic analysis,
      reveals a small positive slope of rho = +0.48. Kinetic isotope effect
      (KIE(intra)) values for oxygenation of [Fe2(mu-O2CAr(Tol))2(O2CAr(Tol))2(N,N
      (C6H5CDH)2en)2] and [Fe2(mu-O2CAr(Tol))2(O2CAr(Tol))2(N,N-(C6H5CD2)(C6H5CH2)en)2]
      are 1.3(1) and 2.2(2) at 23 degrees C, respectively. The positive slope rho and
      low KIE(intra) values are consistent with a mechanism involving one-electron
      transfer from the dangling nitrogen atom in N,N-Bn2en to a transient
      electrophilic diiron intermediate, followed by proton transfer and rearrangement
      to eliminate benzaldehyde.

PMID- 16813408
TI  - Heterometallic Cr-Mn complexes containing cyanide and oxalate bridges.
AB  - Three heterometallic Cr-Mn compounds, {Mn(mu-ox)0.5(H2O) [Cr(phen)(CN)4]}n.n
      H2O.2n CH3OH, (1), {Mn(mu-ox)0.5(H2O)[Cr(bpy)(CN)4]}n.2n H2O x n CH3OH, (2), and
      {Mn(mu-ox)0.5(bpy)[Cr(bpy)(CN)4]}n, (3) (ox = oxalate), containing cyanide and
      oxalate bridges based on building blocks [Cr(L)(CN)4]- (L = phen and 2,2'
      bipyridine) have been prepared. A new approach was first employed to synthesize
      ox-bridged compounds via facile oxidation-hydrolysis reactions of
      diaminomaleonitrile. X-ray crystallography revealed that the structures of 1 and
      2 are similar, where cyano-bridged corrugated ladderlike chains are further
      connected through bis-bidentate oxalato bridges to unique two-dimensional layered
      structures. Of note is that the introduction of 2,2'-bipyridine led to an
      interesting cluster-based chainlike compound (3) with cyano-bridged squares
      [Mn2Cr2] extended by ox bridges. Magnetic studies show antiferromagnetic (AF)
      interaction between cyano-bridged Cr(III)-Mn(II) and ox-bridged Mn(II)-Mn(II)
      ions, with the result that 1 and 2 exhibit AF ordering with spin-flop behaviors
      below 18 and 19 K, respectively.

PMID- 16813409
TI  - Synthesis, structure, and characterization of molybdenum(VI) imido complexes with
      N-salicylidene-2-aminophenol.
AB  - Diimido complexes of the type Mo(NAr)2Cl2(dme) (dme = 1,2-dimethoxyethane) react
      with N-salicylidene-2-aminophenol (sapH2) in methanol in the presence of 2 equiv
      of triethylamine to form complexes with the general formula Mo(NAr)(1,2
      OC6H4NH)(sap). The structures of three of these compounds (NAr = 2,6
      dimethylphenylimido (1), 2,4,6-trimethylphenylimido (2), 2-tert
      butylphenylimido3) have been determined by X-ray crystallography. The
      coordination sphere around the Mo is a distorted octahedron. The oxygen from the
      2-aminophenol is trans to the imido nitrogen, whereas the amido nitrogen and the
      tridentate sap occupy the four equatorial positions. The Mo-N-C imido linkages
      have angles of 167.5(2) degrees (1), 163.2(2) degrees (2), and 162.4(1) degrees
      (3). A precursor complex to the imido-amido complex, Mo(NAr)(sap)(OCH3)2 (4, NAr
      = 2,4,6-trimethylphenylimido), has been isolated and characterized. Compound 4
      reacts with 2-aminophenol to form 2, with 2-aminothiophenol to form Mo(NAr)(1,2
      SC6H4NH)(sap) (5), with catechol to form Mo(NAr)(1,2-OC6H4O)(sap) (6), with
      naphthalene-2,3-diol to form Mo(NAr)(naphthalene-2,3-diolate)(sap) (7), with 1,2
      benzenedithiol to form Mo(NAr)(1,2-SC6H4S)(sap) (8), and with 1,2
      phenylenediamine to form Mo(NAr)(1,2-HNC6H4NH)(sap) (9). The structures of
      compounds 5-9 have been determined by X-ray crystallography. With the exception
      of compound 8, the structures are similar to those of 1,2, and 3, with the
      bidentate ligand occupying one axial and one equatorial position. In 8, 1,2
      benzendithiolate occupies two equatorial positions, and the nitrogen from sap is
      located trans to the imido nitrogen. All complexes were characterized by 1H NMR
      spectroscopy, cyclic voltammetry, and UV-vis spectroscopy. When a solution of 4
      is exposed to moisture-containing air, MoO2(sap)(CH3OH) (10) is formed. The
      structure of 10 was also determined.

PMID- 16813411
TI  - Triple-decker sandwich compounds bearing compact triallyl tripods for molecular
      information storage applications.
AB  - The design of redox-active molecules that afford multistate operation and high
      charge density is essential for molecular information storage applications.
      Triple-decker sandwich compounds composed of two lanthanide metal ions and three
      porphyrinic ligands exhibit a large number of oxidation states within a
      relatively narrow electrochemical window. High charge density requires a small
      footprint upon tethering triple deckers to an electroactive surface. All triple
      deckers examined to date for information storage have been tethered via the
      terminal ligand and have exhibited large footprints (approximately 670 A2). Five
      new homonuclear (Eu or Ce) triple deckers have been prepared (via statistical or
      rational methods) to examine the effect of tether attachment site on molecular
      footprint. Three triple deckers are tethered via the terminal ligand (porphyrin)
      or central ligand (porphyrin or imidazophthalocyanine), whereas two triple
      deckers each bear two tethers, one at each terminal ligand. The tether is a
      compact triallyl tripod. Monolayers of the triple deckers on Si(100) were
      examined by electrochemical and FTIR techniques. Each triple decker exhibited the
      expected four resolved voltammetric waves, owing to formation of the mono-, di-,
      tri-, and tetracations. The electrochemical studies of surface coverage (gamma,
      obtained by integrating the voltammetric waves) reveal that coverages approaching
      10(-10) mol cm(-2), corresponding to a molecular footprint of approximately 170
      A2, are readily achieved for all five of the triple deckers. The surface coverage
      observed for the tripodal functionalized triple deckers is approximately 4-fold
      higher than that obtained for monopodal-functionalized triple deckers (carbon,
      oxygen, or sulfur anchor atoms) attached to either Si(100) or Au(111). The fact
      that similar, relatively high, surface coverages can be achieved regardless of
      the location (or number) of the tripodal tether indicates that the tripodal
      functionalization, rather than the location of the tether, is the primary
      determinant of the packing density.

PMID- 16813410
TI  - Tren-based analogues of bacillibactin: structure and stability.
AB  - Synthetic analogues were designed to highlight the effect of the glycine moiety
      of bacillibactin on the overall stability of the ferric complex as compared to
      synthetic analogues of enterobactin. Insertion of a variety of amino acids to
      catecholamide analogues based on a Tren (tris(2-aminoethyl)amine) backbone
      increased the overall acidity of the ligands, causing an enhancement of the
      stability of the resulting ferric complex as compared to TRENCAM. Solution
      thermodynamic behavior of these siderophores and their synthetic analogues was
      investigated through potentiometric and spectrophotometric titrations. X-ray
      crystallography, circular dichroism, and molecular modeling were used to
      determine the chirality and geometry of the ferric complexes of bacillibactin and
      its analogues. In contrast to the Tren scaffold, addition of a glycine to the
      catechol chelating arms causes an inversion of the trilactone backbone, resulting
      in opposite chiralities of the two siderophores and a destabilization of the
      ferric complex of bacillibactin compared to ferric enterobactin.

PMID- 16813412
TI  - Homologues of the easily ionized compound Mo2(hpp)4 containing smaller bicyclic
      guanidinates.
AB  - Two bicyclic guanidinate ligands consisting of 5,5-membered (tbo) and 5,6
      membered (tbn) rings have been used for the preparation of dimolybdenum
      compounds, such as Mo2(tbo)4 and Mo2(tbo)4Cl, and species containing
      Mo2(tbn)4(n+) with n = 0-2. The compounds with quadruply bonded Mo2(4+) species
      are strong reducing agents and have potentials of about -1 V (vs Ag/AgCl) for the
      Mo2(5+/4+) process. The structure of the THF solvate of Mo2(tbo)4 shows the
      longest Mo-Mo bond distance, 2.1453(4) A, for a quadruply bonded species, and
      this is due to a large divergent angle induced by the geometry of the ligand.
      This distance increases to 2.2305(8) A upon oxidation by CH2Cl2 to Mo2(tbo)4Cl.
      For the 5,6-membered-ring ligand tbn, even though the divergent angle is large
      compared to formamidinate ligands, it is not as large as that in tbo, and the Mo
      Mo distance in Mo2(tbn)4, 2.082(1) A, is in the normal range for paddlewheel
      Mo2(4+) compounds. This distance increases to 2.2233(8) A upon oxidation by O2 in
      CH2Cl2, which forms Mo2(tbn)4Cl2 x CH2Cl2.

PMID- 16813413
TI  - Comparison of the crystal structures and magnetic properties of the low- and high
      temperature forms of AgCuPO4: crystal structure determination, magnetic
      susceptibility measurements, and spin dimer analysis.
AB  - The crystal structure of the low-temperature form of AgCuPO4 (i.e., alpha
      AgCuPO4) was determined by powder X-ray diffraction and was compared with that of
      the high-temperature form of AgCuPO4 (i.e., beta-AgCuPO4). The magnetic
      properties of the two forms were examined by measuring their magnetic
      susceptibilities and evaluating the relative strengths of their spin-exchange
      interactions on the basis of spin-dimer analysis. Both forms of AgCuPO4 have
      layers of Cu2P2O8 alternating with silver-atom double layers; beta-AgCuPO4 has
      two Cu2P2O8 layers per unit cell, while alpha-AgCuPO4 has one. The coordinate
      environment of each Cu2+ ion is close to being a distorted square pyramid in
      alpha-AgCuPO4, but it is close to being a distorted trigonal bipyramid in beta
      AgCuPO4. The magnetic susceptibilities of alpha- and beta-AgCuPO4 are well
      simulated by an antiferromagnetic alternating-chain model, which leads to J/k(B)
      = -146.1 K and alphaJ/k(B) = -75.8 K for alpha-AgCuPO4, and J/k(B) = -82.6 K and
      alphaJ/k(B) = -31.7 K for beta-AgCuPO4 (with the convention in which the spin
      exchange parameter between two adjacent spin sites is written as 2J). The spin
      gaps, delta/k(B), obtained from these parameters are 93.7 K for alpha-AgCuPO4 and
      62.3 K for beta-AgCuPO4. The strongest spin exchange in both forms of AgCuPO4
      comes from a super-superexchange path, and this interaction is stronger for alpha
      AgCuPO4 than for beta-AgCuPO4 by a factor of approximately 2, in good agreement
      with the experiment. Our analysis supports the use of this model for beta-AgCuPO4
      and indicates that the spin lattice of alpha-AgCuPO4 would be better described by
      a two-dimensional net made up of weakly interacting alternating chains.

PMID- 16813415
TI  - Synthesis, structural characterization, gas sorption and guest-exchange studies
      of the lightweight, porous metal-organic framework alpha-[Mg3(O2CH)6].
AB  - Unsolvated magnesium formate crystallizes upon reaction of the metal nitrate with
      formic acid in DMF at elevated temperatures. Single-crystal XRD studies reveal
      the formation of [Mg3(O2CH)6 [symbol: see text] DMF], 1, a metal-organic
      framework with DMF molecules filling the channels of an extended diamondoid
      lattice. The DMF molecules in 1 can be entirely removed without disruption to the
      framework, giving the guest-free material alpha-[Mg3(O2CH)6], 2. Compound 2 has
      been characterized by both powder and single-crystal XRD studies.
      Thermogravimetric analyses of 1 show guest loss from 120 to 190 degrees C, with
      decomposition of the sample at approximately 417 degrees C. Gas sorption studies
      using both N2 and H2 indicate that the framework displays permanent porosity. The
      porosity of the framework is further demonstrated by the ability of 2 to uptake a
      variety of small molecules upon soaking. Single-crystal XRD studies have been
      completed on the six inclusion compounds [Mg3(O2CH)6 [symbol: see text] THF], 3;
      [Mg3(O2CH)6 [symbol: see text] Et2O], 4; [Mg3(O2CH)6 [symbol: see text] Me2CO],
      5; [Mg3(O2CH)6 [symbol: see text] C6H6], 6; [Mg3(O2CH)6 [symbol: see text] EtOH],
      7; and [Mg3(O2CH)(6) [symbol: see text] MeOH], 8. Analyses of the metrical
      parameters of 1-8 indicate that the framework has the ability to contract or
      expand depending on the nature of the guest present.

PMID- 16813414
TI  - Model peptides based on the binding loop of the copper metallochaperone Atx1:
      selectivity of the consensus sequence MxCxxC for metal ions Hg(II), Cu(I),
      Cd(II), Pb(II), and Zn(II).
AB  - The amino acid sequence MxCxxC is conserved in many soft-metal transporters that
      are involved in the control of the intracellular concentration of ions such as
      Cu(I), Hg(II), Zn(II), Cd(II), and Pb(II). A relevant task is thus the
      selectivity of the motif MxCxxC for these different metal ions. To analyze the
      coordination properties and the selectivity of this consensus sequence, we have
      designed two model peptides that mimic the binding loop of the copper chaperone
      Atx1: the cyclic peptide P(C) c(GMTCSGCSRP) and its linear analogue P(L) (Ac
      MTCSGCSRPG-NH2). By using complementary analytical and spectroscopic methods, we
      have demonstrated that 1:1 complexes are obtained with Cu(I) and Hg(II), whereas
      1:1 and 1:2 (M:P) species are successively formed with Zn(II), Cd(II), and
      Pb(II). The complexation properties of the cyclic and linear peptides are very
      close, but the cyclic compound provides systematically higher affinity constants
      than its unstructured analogue. The introduction of a xPGx motif that forms a
      type II beta turn in P(C) induces a preorganization of the binding loop of the
      peptide that enhances the stabilities of the complexes (up to 2 orders of
      magnitude difference for the Hg complexes). The affinity constants were measured
      in the absence of any reducing agent that would compete with the peptides and
      range in the order Hg(II) > Cu(I) >> Cd(II) > Pb(II) > Zn(II). This sequence is
      thus highly selective for Cu(I) compared to the essential ion Zn(II) that could
      compete in vivo or compared to the toxic ions Cd(II) and Pb(II). Only Hg(II) may
      be an efficient competitor of Cu(I) for binding to the MxCxxC motif in
      metalloproteins.

PMID- 16813416
TI  - Directed synthesis of noncentrosymmetric molybdates using composition space
      analysis.
AB  - A systematic investigation of the factors governing the reaction product
      composition, hydrogen bonding, and symmetry was conducted in the MoO3/3
      aminoquinuclidine/H2O system. Composition space analysis was performed through 36
      individual reactions under mild hydrothermal conditions using racemic 3
      aminoquinuclidine. Single crystals of three new compounds, [C7H16N2][Mo3O10] x
      H2O, [C7H16N2]2[Mo8O26] x H2O, and [C7H16N2]2[Mo8O26] x 4 H2O, were grown. The
      relative phase stabilities for these products are dependent upon the reactant
      mole fractions in the initial reaction gel. This phase stability information was
      used to direct the synthesis of two new noncentrosymmetric compounds, using
      either (S)-(-)-3-aminoquinuclidine dihydrochloride or (R)-(+)-3-aminoquinuclidine
      dihydrochloride. [(R)-C7H16N2]2[Mo8O26] and [(S)-C7H16N2]2[Mo8O26] both
      crystallize in the noncentrosymmetric space group P2(1) (No. 4), which has the
      polar crystal class 2 (C2). The second-harmonic generation activities were
      measured on sieved powders. The structure-directing properties of the molybdate
      components in each compound were determined using bond valence sums. The
      structures of all five compounds were determined using single-crystal X-ray
      diffraction.

PMID- 16813417
TI  - Conformationally gated photoinduced processes within photosensitizer-acceptor
      dyads based on osmium(II) complexes with triarylpyridinio-functionalized
      terpyridyl ligands: insights from theoretical analysis.
AB  - A theoretical analysis, based on density functional theory, has been carried out
      to study photoinduced processes within a recently experimentally characterized
      (Laine, P. P.; Bedioui, F.; Loiseau, F.; Chiorboli, C.; Campagna, S. J. Am. Chem.
      Soc. 2006, http://dx.doi.org/10.1021/ja058357w.) series of Os(II) bis-tpy
      complexes (tpy = 2,2':6'2' '-terpyridine) functionalized by 2,4,6
      triarylpyridinium groups, TP+. These dyad systems, designed to produce a charge
      separated state (CSS) upon light excitation, are made up of a photosensitizer
      unit (P, the metal complex) and a tunable acceptor unit (A, the TP+). A full ab
      initio characterization of the electronic and structural properties of the lowest
      lying triplet excited states, as well as of the CSS, allowed for a complete
      rationalization of the photoinduced processes taking place within the dyads.
      Among salient insights, theory allowed (i) substantiation of the inner P
      structural planarization as the relaxation mode of the MLCT states, (ii)
      confirmation of the existence of a ligand-centered triplet excited state (3LC)
      shown to essentially involve the nitro substituent of A (TP+-NO2) and lying very
      close in energy to the P-centered 3MLCT state, and (iii) a demonstration that the
      energy of the 3LC level is independent of intercomponent tilt angle (theta1). On
      this basis, the occurrence of a reversible electronic energy transfer between the
      3MLCT and the 3LC states could be substantiated and shown to depend on the
      intramolecular conformation represented by theta1, which actually governs their
      electronic coupling (essentially via the degree of intercomponent conjugation).
      These computational issues were checked against experimental data already
      available and the results of a specifically undertaken photophysical study.
      Finally, CSS formation has been confirmed by studying the spin density patterns
      of reduced nitro-derivatized dyads. Taken together, these findings accurately
      account for the different excited-state behaviors of the dyads as a function of
      the level of structural restriction of their intercomponent conformation (and
      related amplitude for torsional fluctuations), thus providing theoretical
      evidence of conformationally gated photoinduced electron- and energy-transfer
      processes.

PMID- 16813418
TI  - Luminescent amidate-bridged one-dimensional platinum(II)-thallium(I) coordination
      polymers assembled via metallophilic attraction.
AB  - The neutral square-planar complexes [Pt(RNH2)2(NHCO(t)Bu)2] (R = H, 1; Et, 2) and
      [Pt(DACH)(NHCO(t)Bu)2] (DACH = 1,2-diaminocyclohexane, 3) act as metalloligands
      and make bonds to closed-shell Tl(I) ions to afford one- and two-dimensional
      platinum-thallium oligomers or polymers based on heterobimetallic backbones. A
      series of heteronuclear platinum(II)-thallium(I) complexes have been synthesized
      and structurally characterized. The structures of the Pt-Tl compounds resulted
      from [Pt(RNH2)2(NHCO(t)Bu)2] and TlX [X = NO3(-), ClO4(-), PF6(-), and
      Cp2Fe(CO2)2(2-)] are dependent on both counteranions and the amine substituents.
      The compounds [Pt(NH3)2(NHCO(t)Bu)2Tl]X (X = NO3(-), 8; ClO4(-), 9) adopt one
      dimensional zigzag chain structures consisting of repeatedly stacked
      [Pt(NH3)2(NHCO(t)Bu)2Tl]+ units, whereas [{Pt(NH3)2(NHCO(t)Bu)2}2Tl2]X2 (X = PF6(
      ), 10) consists of a helical chain. Compound 3 reacts with Tl+ to give
      [{Pt(DACH)(NHCO(t)Bu)2}2Tl](NO3) x [Pt(DACH)(NHCO(t)Bu)2] x 3 H2O (14) and one
      dimensional polymeric [{Pt(DACH)(NHCO(t)Bu)2}2Tl2]X2 (X = ClO4(-), 15; PF6(-),
      16). Reactions of [Pt(DACH)(NHCOCH3)2] with Tl+ ions afford one-dimensional
      coordination polymers [{Pt(DACH)(NHCOCH3)2}2Tl2]X2 (X = NO3(-), 17; ClO4(-), 18;
      PF6(-), 19). The polymeric [{Pt(DACH)(NHCOR')2}2Tl2]2+ (R = CH3, (t)Bu) complexes
      adopt helical structures, which are generated around the crystallographic 2(1)
      screw axis. The distance between the coils corresponds to the unit cell length,
      which ranges from 22.58 to 22.68 A. The platinum-thallium bond distances fall in
      a narrow range around 3.0 A. The complexes derived from [Pt(NH3)2(NHCO(t)Bu)2]
      are luminescent at 77 K. The trinuclear complexes [{Pt(RNH2)(NHCO(t)Bu)2}2Tl]+ do
      not emit at room temperature but are emissive at 77 K, whereas the polymeric
      platinum-thallium complexes containing 1,2-diaminocyclohexane are intensively
      luminescent at both room temperature and 77 K. The color variations are
      interesting; 15 exhibits intense yellow-green, 16 exhibits green, and 17-19
      exhibit blue luminescence. The presence of bonding between platinum and thallium
      is supported by the short metal-metal separations and the strong low-energy
      luminescence of these compounds in their solid states.

PMID- 16813419
TI  - Spectroscopic characterization of primary and secondary phosphine ligation on
      ruthenium(II) complexes.
AB  - Ruthenium(II) complexes of the primary phosphines PH2Fc and PH2CH2Fc and the
      secondary phosphine PH(CH2Fc)2, including [(p-cymene)RuCl(L)2](PF6) (p-cymene = p
      iPrC6H4Me, L = PH2CH2Fc and PH(CH2Fc)2, 2b and 2c, respectively) and trans
      [RuCl2(L)4] (L = PH2Fc, PH2CH2Fc, and PH(CH2Fc)2, 3a-c, respectively) were
      prepared and characterized by IR, 1H NMR, and 31P NMR spectroscopy. 3b was
      additionally characterized by X-ray crystallography. The spectroscopic effects of
      phosphine ligation were determined. Characteristic downfield shifts of the 31P
      NMR resonances and increases in energy of the nu(P-H) modes were observed in all
      cases. Iterative fitting of coupling constants to second-order NMR spectra also
      resulted in a complete elucidation of 31P-1H and 31P-31P couplings. This analysis
      provides a basis for considering the influence of coordinate bonding on the
      observed 1J(PH) and 2J(PP) constants.

PMID- 16813420
TI  - Facile synthesis of unsymmetrical 9-phospha- and 9-arsafluorenes.
AB  - Unsymmetrical 9-chloro-9-phosphafluorenes (dibenzophospholes) and 9-chloro-9
      arsafluorenes (dibenzoarsoles) have been obtained by simple thermolysis of m
      terphenyldichlorophosphines and -arsines in close to quantitative yields. The
      reaction temperatures are about 200 degrees C for the phosphines and 140 degrees
      C for the arsine, and the reactions are complete within 5 min. Alternatively,
      these compounds can be synthesized through an AlCl3-catalyzed Friedel-Crafts type
      ring-closure reaction at low temperatures, but this method suffers from difficult
      workup procedures. The P(As)-Cl functionality is readily alkylated. Methylation
      of m-xylyl derivative 4 afforded 1-(3,5-dimethylphenyl)-6,8,9-trimethyl-9
      phosphafluorene, 11. The latter compound formed the complexes 11 x Fe(CO)4, 12,
      and 11 x RuCl2(eta(6)-p-cymene), 13, indicating its good donor properties. The
      new compounds have been characterized by 1H, 13C{1H}, and 31P{1H} NMR
      spectroscopy; mass spectrometry; and single-crystal X-ray crystallography in the
      case of 11, 12, and 13.

PMID- 16813421
TI  - Synthesis of the novel [W3PdS4H3(dmpe)3(CO)]+ cubane cluster and kinetic studies
      on the substitution of coordinated hydrides in acidic media.
AB  - Reaction of the incomplete cuboidal [W3S4H3(dmpe)3]+ cluster with a Pd(0) complex
      under a CO atmosphere produces a rare example of a heterodimetallic hydrido
      cluster of formula [W3PdS4H3(dmpe)3(CO)]+ ([1]+). There are not significant
      changes in the W-W bond lengths on going from the trinuclear to the tetranuclear
      cluster. The average W-W and W-Pd bond distances of 2.769[10] and 2.90[2] A,
      respectively, are consistent with the presence of single bonds between metal
      atoms. The heterodimetallic [1]+ complex is easier to oxidize and more difficult
      to reduce than its trinuclear precursor, which reflects the electron-donating
      capability of the Pd(CO) fragment. However, mechanistic studies on the reaction
      of [1]+ with acids show a lower basicity for this complex in comparison with that
      of its trinuclear precursor, so there is a major electron-density rearrangement
      within the cluster core upon Pd(CO) coordination. This rearrangement is also
      reflected in an unusual expansion of the sulfur tetrahedron within the W3PdS4
      core with the concomitant elongation of the W-S bond distances by 0.04 A with
      respect to the analogous bond lengths in the trinuclear precursor. For those
      thermodynamically favored proton-transfer processes, the reaction mechanism of
      [1]+ with acids is quite similar to that observed for the incomplete trinuclear
      cluster, with only small changes in the rate constants. The reaction of [1]+ with
      HCl in acetonitrile/water mixtures produces [W3PdS4Cl3(dmpe)3(CO)]+ ([2]+) in two
      kinetically distinguishable steps. Proton transfer occurs in the initial step, in
      which the W-H bonds are attacked by the acid to yield dihydrogen-bonded adducts
      that are further attacked by an acetonitrile molecule to give
      [W3PdS4(CH3CN)3(dmpe)3(CO)]4+ and dihydrogen. The nature of processes involved in
      the second step are not well-understood with the present data, although it is
      very likely that these correspond to some secondary processes. In the third
      resolved step, the coordinated CH3CN ligands in [W3PdS4(CH3CN)3(dmpe)3(CO)]4+ are
      substituted by Cl- to afford the final [2]+ product. No reaction is observed
      between [1]+ and HCl in neat acetonitrile, whereas the product of the reaction of
      [1]+ with HBF4 or Hpts (pts- = p-toluenesulfonate) in this solvent is
      [W3PdS4(CH3CN)3(dmpe)3(CO)]4+. The reaction occurs in a single kinetic step with
      a first- (Hpts) or second-order (HBF4) dependence with respect to the acid. The
      first- and second-order acid dependences can be interpreted through the initial
      formation of dihydrogen adducts with one or two acid molecules, respectively.

PMID- 16813422
TI  - DFT analysis of co-alkyl and co-adenosyl vibrational modes in B12-cofactors.
AB  - Density functional theory (DFT)-based normal mode calculations have been carried
      out on models for B12-cofactors to assign reported isotope-edited resonance Raman
      spectra, which isolate vibrations of the organo-Co group. Interpretation is
      straightforward for alkyl-Co derivatives, which display prominent Co-C stretching
      vibrational bands. DFT correctly reproduces Co-C distances and frequencies for
      the methyl and ethyl derivatives. However, spectra are complex for adenosyl
      derivatives, due to mixing of Co-C stretching with a ribose deformation
      coordinate and to activation of modes involving Co-C-C bending and Co-adenosyl
      torsion. Despite this complexity, the computed spectra provide a satisfactory re
      assignment of the experimental data. Reported trends in adenosyl-cobalamin
      spectra upon binding to the methylmalonyl CoA mutase enzyme, as well as on
      subsequent binding of substrates and inhibitors, provide support for an
      activation mechanism involving substrate-induced deformation of the adenosyl
      ligand.

PMID- 16813423
TI  - Effects of methanol on the thermodynamics of iron(III)
      [tetrakis(pentafluorophenyl)]porphyrin chloride dissociation and the creation of
      catalytically active species for the epoxidation of cyclooctene.
AB  - In a previous study, the authors showed that iron(III)
      [tetrakis(pentafluorophenyl)]porphyrin chloride [(F20TPP)FeCl] is catalytically
      inactive for cyclooctene epoxidation by hydrogen peroxide in acetonitrile but is
      catalytically active if the solvent contains methanol. It was suggested that the
      precursor to the active species is (F20TPP)Fe(OCH3) in methanol-containing
      solvents. The present study was aimed at evaluating this hypothesis.
      (F20TPP)Fe(OCH3) was synthesized and characterized by 1H NMR but was found to be
      inactive in both acetonitrile and methanol. Further investigation of the
      interactions of (F20TPP)FeCl with methanol in acetonitrile/methanol mixtures was
      then carried out using NMR. Two species, characterized by 1H NMR resonances at 82
      and 65 ppm, were observed. The first resonance is attributed to the beta-pyrrole
      protons on molecularly dissolved (F20TPP)FeCl, whereas the second is attributed
      to beta-pyrrole protons of [(F20TPP)Fe]+ cations that are stabilized by
      coordination with a molecule of methanol, viz., [(F20TPP)Fe(CH3OH)]+. The
      relative concentration of [(F20TPP)Fe(CH3OH)]+ increases as the fraction of
      methanol in the solvent increases, suggesting that methanol facilitates the
      dissociation of (F20TPP)FeCl into cations and anions. A thermodynamic model of
      the dissociation is proposed and found to describe successfully the experimental
      observation over a range of solvent compositions, porphyrin concentrations, and
      temperatures. UV-visible spectroscopy was also used to validate the developed
      model. In addition, the observed rate constant for cyclooctene epoxidation was
      found to be proportional to the concentration of [(F20TPP)Fe(CH3OH)]+ calculated
      using the thermodynamic model, suggesting that this intermediate is a precursor
      to the species that catalyzes olefin epoxidation. The catalytic activity of
      [(F20TPP)Fe(CH3OH)]+ was further confirmed through experiments in which
      (F20TPP)Fe(OCH3) dissolved in methanol was reacted with HCl(aq). This reaction
      produced a product with an NMR peak at 65 ppm attributable to
      [(F20TPP)Fe(CH3OH)]+, and this mixture was found to have activity for cyclooctene
      epoxidation similar to that of (F20TPP)FeCl dissolved in methanol.

PMID- 16813424
TI  - Remarkably efficient hydrolysis of methylparathion catalyzed by [2-(2
      pyridyl)phenyl-C,N]palladium(II) complexes.
AB  - The reaction of the palladium(II) acetate derivative [Pd(NwedgeC)(OAc)]2 (NwedgeC
      = (NC5H4-2-C6H4(C2,N) or (2-(2-pyridyl)-phenyl-C,N)) with methylparathion and
      water in THF leads to the formation of [Pd(NwedgeC)(mu-SP(=O)(OCH3)2)]2 (1),
      which reacts with PPh3 in THF to afford mononuclear complex
      [Pd(NwedgeC)(SP(=O)(OCH3)2)(PPh3)] (2). Compounds 1 and 2 have been characterized
      by 1H, 13C, and 31P NMR spectroscopy; elemental analysis; and single-crystal X
      ray diffraction. When dissolved in water, 1 serves as a precatalyst for the
      hydrolysis of methylparathion. Kinetic and spectroscopic studies suggest that
      compound 1 dissociates in aqueous solution to afford cationic diaqua complex
      [Pd(NwedgeC)(OH2)2]+ (A). At basic pH, A is converted into its deprotonated form
      [Pd(NwedgeC)(OH2)(OH)] (B), which dimerizes to afford a dinuclear complex,
      presumably [Pd(NwedgeC)(mu-OH)]2 (C). At pH 7, the reaction is first order in
      substrate and first order in palladium catalyst A, with k2 = 146 +/- 9 M(-1) s(
      1) at 303 K. At more-basic pH, the reaction rate increases and shows an apparent
      half-order dependence in palladium catalyst. These observations suggest that the
      active form of the catalyst at basic pH is B, whose concentration is controlled
      by an equilibrium with inactive C. Analysis of the data obtained at pH 9 yields a
      dimer formation constant K(f) = [C]/[B]2 = (6.6 +/- 5.6) x 10(6) M(-1) and a
      second-order rate constant k2 of (8.6 +/- 3.6) x 10(3) M(-1) s(-1) at 298 K. The
      pH dependence of the reaction rate as well as a spectroscopic titration indicates
      that the pKa of A is in the 9.5-9.7 range. Determination of the activation
      parameters at both pH 7 and 9 suggests that catalysis occurs via an associative
      mechanism whose rate-determining step involves the substitution of a water ligand
      of A by a molecule of methylparathion at neutral pH and nucleophilic attack of
      the phosphorus center of methylparathion by a hydroxide ligand of B at basic pH.

PMID- 16813425
TI  - Iron(III) coordination properties of a pyoverdin siderophore produced by
      Pseudomonas putida ATCC 33015.
AB  - The iron complexation of a fluorescent green pyoverdin siderophore produced by
      the environmental bacterium Pseudomonas putida was characterized by solution
      thermodynamic methods. Pyoverdin binds iron through three bidentate chelate
      groups, a catecholate, a hydroxamate, and an alpha-hydroxycarboxylic acid. The
      deprotonation constants of the free pyoverdin and Fe(III)-pyoverdin complex were
      determined through a series of potentiometric and spectrophotometric experiments.
      The ferric complex of pyoverdin forms at very low pH (pH < 2), but full iron
      coordination does not occur until neutral pH. The calculated pM value of 25.13 is
      slightly lower than that for pyoverdin PaA (pM = 27), which coordinates iron by a
      catecholate and two hydroxamate groups. The redox potential of Fe-pyoverdin was
      found to be very pH sensitive. At high pH (approximately pH 9-11) where pyoverdin
      coordinates Fe in a hexadentate mode the redox potential is -0.480 V (NHE);
      however, at neutral pH where full Fe coordination is incomplete, the redox
      potential is more positive (E(1/2) = -0.395 V). The positive shift in the redox
      potential and the partial dissociation of the Fe-pyoverdin complex with pH
      decrease provides a path toward in vivo iron release.

PMID- 16813426
TI  - Si-N bond hydrolysis furnishes a planar 4-coordinate 14-electron Ru(II) complex
      with a triplet ground state.
AB  - Reaction of stoichiometric (2:1) water with [(tBu2PCH2SiMe2)2N]Ru(OSO2CF3)
      produces planar, 14-valence-electron spin triplet trans-Ru(tBu2PCH2SiMe2O)2. A
      possible mechanism for this hydrolysis is discussed. This molecule reacts rapidly
      with CO to give a monocarbonyl, then a cis-dicarbonyl. Reaction with HCCR (R = H
      or Ph) yields the vinylidene (tBu2PCH2SiMe2O)2Ru=C=CHR.

PMID- 16813427
TI  - Binuclear cyclopentadienylmetal nitrosyls of iron, cobalt, and nickel: comparison
      with related carbonyl derivatives.
AB  - The binuclear cyclopentadienylmetal nitrosyls and carbonyls Cp2M2(AO)n (A = N, M
      = Fe, Co, Ni; A = C, M = Ni; n = 2, 1) are studied by density functional theory
      using the B3LYP and BP86 functionals. In general, structures with bridging AO
      ligands are energetically preferred over those with terminal AO ligands. Thus,
      the global minima for Cp2M2(AO)2 are all found to have closely related axial
      dimetallocene structures with two symmetrically bridging AO ligands but variable
      planarity of the central M(mu-AO)2M units. Similarly, the single AO ligands in
      the global minima for Cp2M2(AO) are found to bridge symmetrically the pair of
      metal atoms. However, structures with terminal AO groups and a single bridging Cp
      ligand are also found at accessible energies for CpM2(NO)(mu-Cp) (M = Fe and Co)
      and CpNi2(CO)(mu-Cp). The metal-metal bond distances in Cp2M2(AO)n derivatives
      correlate reasonably well with the requirements of the 18-electron rule. In this
      connection, the unusual dimer Cp2Ni2(mu-NO)2 has a Ni-Ni bond distance suggestive
      of a single bond and geometry suggesting one one-electron donor bridging NO group
      and one three-electron donor bridging NO group. However, dissociation of
      Cp2Ni2(mu-NO)2 into the well-known stable monomer CpNiNO is highly favored
      energetically.

PMID- 16813428
TI  - Stabilization of a monomethyl orthomolybdate in the binding pocket of a dinuclear
      cobalt complex.
AB  - The ability of the dinuclear Co(II) complex [(L(Me))Co(II)2(mu-Cl)]+ [1; (L(Me))2
      = 3,6,9,17,20,23-hexamethyl-3,6,9,17,20,23-hexaaza-29,30-dithiol-13,27-di-tert
      butyltricyclo[23.3.1(11.15)]triaconta-1(28),11,13,15(30),25,26-hexaene] to bind
      tetrahedral oxoanions of the transition metal has been investigated. Two new
      complexes, [(L(Me))Co(II)2(mu-MoO4)] (2) and [(L(Me))Co(II)2(mu
      MoO3(OMe))]2[Mo4O10(OMe)6] (3), were prepared by substitution reactions of 1 with
      (n-Bu4N)2MoO4 in MeCN or with MoO3 x 2 H2O/NEt3 in MeOH. Both compounds were
      characterized by X-ray crystallography. The dioctahedral complex 2 features a
      mu(1,3)-bridging MoO4(2-) unit, whereas the cation in 3 hosts an unprecedented
      mu(1,3)-MoO3(OMe)- motif, demonstrating that four-coordinate molybdate esters can
      be stabilized in the binding pocket of the bowl-shaped [(L(Me))Co(II)2]2+
      complex. The results of IR, UV/vis, and cyclic voltammetry measurements are also
      reported.

PMID- 16813429
TI  - Synthesis and characterization of novel "3 + 2" oxorhenium complexes,
      ReO[SNO][NN].
AB  - The present paper deals with the synthesis and structural characterization of
      novel neutral oxorhenium(V) complexes of the general formula ReO[SNO][NN]. The
      simultaneous action of the tridentate SNO ligand, N-(2-mercaptoacetyl)glycine
      (1), and the bidentate NN ligand, N-phenylpyridine-2-aldimine (2), on
      ReOCl3(PPh3)2 leads to the formation of two isomers 4a and 4b of the general
      formula ReO[SNO][NN], as a result of the different orientations of the NN ligand.
      In both cases, the SNO donor atoms of the tridentate ligand occupy the three
      positions in the equatorial plane of the distorted octahedron, whereas the oxo
      group is always directed toward one of the apical positions. In the first isomer,
      4a, the imino nitrogen of the NN ligand occupies the fourth equatorial position
      and the pyridine type nitrogen is directed trans to the oxo group, while in the
      second isomer, 4b, the imino nitrogen of the NN ligand occupies the apical
      position trans to the oxo group and the pyridine type nitrogen completes the
      equatorial plane of the distorted octahedron. The [SNO][NN] mixed-ligand system
      was applied in the synthesis of the oxorhenium complex 5 in which the 1-(2
      methoxyphenyl)piperazine moiety, a fragment of the true 5-HT1A antagonist WAY
      100635, has been incorporated in the NN bidentate ligand (NN is N-{3-[4-(2
      methoxyphenyl)piperazin-1-yl]propyl}pyridine-2-aldimine). In this case, high
      performance liquid chromatography and NMR showed the existence of one isomer, 5,
      in which the pyridine nitrogen is trans to the oxo core, as demonstrated by
      crystal structure analysis.

PMID- 16813430
TI  - Synthesis and characterization of novel fluorinated poly(oxomolybdates).
AB  - Two novel poly(oxofluoromolybdate) clusters, [Mo6O18F6]6- and [Mo7O22F3]5-, have
      emerged from systematic field studies on the hydrothermal fluorination of
      poly(oxometalates). They are accessible via the hydrothermal treatment of Mo(VI)
      based precursors in the presence of MF additives (M = Li, Na, Cs, NMe4). The new
      fluorinated polyanions are stabilized by specific alkali-cation combinations, and
      their packing motifs can be tuned through the careful choice of cations and
      synthetic parameters. The [Mo6O18F6]6- anion can be described as a cored and
      fluorinated form of the Anderson-Evans cluster type. It is stabilized by the
      interaction of two alkali cations with the fluorinated faces of the ring-shaped
      anion. The partial replacement of these capping alkali cations by the bulky,
      organic NMe4(+) cation leads to the formation of [Mo7O22F3](5-)-based compounds.
      Thus, the extent of fluorination can be controlled through the polarizability of
      the cationic environment: in the [Mo7O22F3]5- anion, half of the fluoride atoms
      of the [Mo6O18F6]6- anion are replaced by a capping MoO4 tetrahedron, thereby
      rendering this anion a fluorinated, lacunar derivative of the alpha-[Mo8O26]4-
      octamolybdate anion. All compounds have been structurally characterized by single
      crystal X-ray diffraction and solid-state NMR spectroscopy. The templating role
      of the alkali cations is discussed and explained with the help of electrostatic
      calculations.

PMID- 16813431
TI  - Increasing the ordering temperatures in oxalate-based 3D chiral magnets: the
      series [Ir(ppy)2(bpy)][M(II)M(III)(ox)3] x 0.5 H2O (M(II)M(III) = MnCr, FeCr,
      CoCr, NiCr, ZnCr, MnFe, FeFe); bpy = 2,2'-bipyridine; ppy = 2-phenylpyridine; ox
      = oxalate dianion).
AB  - The synthesis, structure, and physical properties of a novel series of oxalate
      based bimetallic magnets obtained by using the Ir(ppy)2(bpy)]+ cation as a
      template of the bimetallic [M(II)M(III)(ox)3]- network are reported. The
      compounds can be formulated as [Ir(ppy)2(bpy)][M(II)Cr(III)(ox)3] x 0.5 H2O
      (M(II) = Ni, Mn, Co, Fe, and Zn) and [Ir(ppy)2(bpy)]-[M(II)Fe(III)(ox)3] x 0.5
      H2O (M(II) = Fe, Mn) and crystallize in the chiral cubic space group P4(1)32 or
      P4(3)32. They show the well-known 3D chiral structure formed by M(II) and M(III)
      ions connected through oxalate anions with [Ir(ppy)2(bpy)]+ cations and water
      molecules in the holes left by the oxalate network. The M(II)Cr(III) compounds
      behave as soft ferromagnets with ordering temperatures up to 13 K, while the
      Mn(II)Fe(III) and Fe(II)Fe(III) compounds behave as a weak ferromagnet and a
      ferrimagnet, respectively, with ordering temperatures of 31 and 28 K. These
      values represent the highest ordering temperatures so far reported in the family
      of 3D chiral magnets based on bimetallic oxalate complexes.

PMID- 16813432
TI  - Novel tert-butyl-tris(3-hydrocarbylpyrazol-1-yl)borate ligands: synthesis,
      spectroscopic studies, and coordination chemistry.
AB  - The lithium (1) and thallium (2) salts of five new tert-butyl-tris(3
      hydrocarbylpyrazol-1-yl)borate ligands [t-BuTp(R)]- (R = H, a; Me, b; i-Pr, c; t
      Bu, d; Ph, e) have been synthesized and characterized. Because of steric
      congestion at B, the reaction between t-BuBH3Li x 0.5 Et2O and excess 2,5
      dimethylpyrazole Hpz(Me2) afforded the bis-pz(Me2) derivative, Tl[t-BuBH(3,5
      Me2pz)2] (3) after metathesis with TlNO3. The compounds were characterized by
      elemental analysis and NMR spectroscopy. The Li salts 1a and 1c exhibit fluxional
      behavior on the NMR time scale in solution at room temperature. The solid-state
      7Li and 11B NMR spectra of 1c suggest that this salt exists as a mixture of axial
      and equatorial isomers. The partial hydrolysis of 1d afforded the dimeric Li
      complex {Li[t-BuB(pz(t-Bu))2(mu-OH)]}2 (4). The crystal structure of 4 shows two
      Li cations encapsulated by the heteroscorpionate [t-BuB(OH)(3-t-Bupz)2]- ligands.
      A salt elimination reaction between FeCl2(THF)1.5 and 2 equiv of Li[t-BuTp(R)] (R
      = H, Me) followed by an in situ one-electron oxidation produced good yields of
      the homoleptic, paramagnetic low-spin iron(III) complexes [Fe(t-BuTp)2]PF6 (5)
      and [Fe(t-BuTp(Me))2]PF6 (6) that were characterized by elemental analyses,
      magnetic susceptibility measurements in solution and the solid phase, 1H NMR,
      high-resolution mass spectrometry, Mossbauer spectroscopy, and single-crystal X
      ray diffraction. The crystals are composed of discrete molecular units with the
      central Fe(III) ion in an almost perfectly octahedral coordination to six
      nitrogen atoms. Compound 5 has the shortest Fe-N bond lengths ever reported for
      [Fe(RTp(R)')2]+-type compounds.

PMID- 16813433
TI  - Synthesis, structural characterization, reactivity, and thermal stability of
      [eta(5):sigma-Me2C(C5H4)(C2B10H10)]Ti(R)(NMe2).
AB  - Reaction of [eta:(5)sigma-Me2C(C5H4)(C2B10H10)]TiCl(NMe2) (1) with 1 equiv of
      PhCH2K, MeMgBr, or Me3SiCH2Li gave corresponding organotitanium alkyl complexes
      [eta:(5)sigma-Me2C(C5H4)(C2B10H10)]Ti(R)(NMe2) (R = CH2Ph (2), CH2SiMe3 (4), or
      Me (5)) in good yields. Treatment of 1 with 1 equiv of n-BuLi afforded the
      decomposition product {[eta:(5)sigma-Me2C(C5H4)(C2B10H10)]Ti}2(mu-NMe)(mu:sigma
      CH2NMe) (3). Complex 5 slowly decomposed to generate a mixed-valence dinuclear
      species {[eta:(5)sigma-Me2C(C5H4)(C2B10H10)]Ti}2(mu-NMe2)(mu:sigma-CH2NMe) (6).
      Complex 1 reacted with 1 equiv of PhNCO or 2,6-Me2C6H3NC to afford the
      corresponding monoinsertion product [eta:(5)sigma
      Me2C(C5H4)(C2B10H10)]Ti(Cl)[eta(2)-OC(NMe2)NPh] (7) or [eta:(5)sigma
      Me2C(C5H4)(C2B10H10)]Ti(Cl)[eta(2)-C(NMe2)=N(2,6-Me2C6H3)] (8). Reaction of 4 or
      5 with 1 equiv of R'NC gave the titanium eta(2)-iminoacyl complexes [eta:(5)sigma
      Me2C(C5H4)(C2B10H10)]Ti(NMe2)[eta(2)-C(R)=N(R')] (R = CH2SiMe3, R' = 2,6-Me2C6H3
      (9) or tBu (10); R = Me, R' = 2,6-Me2C6H3 (11) or tBu (12)). The results
      indicated that the unsaturated molecules inserted into the Ti-N bond only in the
      absence of the Ti-C(alkyl) bond and that the Ti-C(cage) bond remained intact. All
      complexes were fully characterized by various spectroscopic techniques and
      elemental analyses. Molecular structures of 2, 3, 6-8, and 10-12 were further
      confirmed by single-crystal X-ray analyses.

PMID- 16813434
TI  - Synthesis of tubular titanate via a self-assembly and self-removal process.
AB  - Novel morphology titanate tubes were successfully synthesized via a self-assembly
      and self-removal process. After the product was treated by calcinating and
      washing, crystalline TiO2 tubes were obtained. In this study, two new concepts
      are applied to design the synthetic route: (i) titanium glycolate rods obtained
      from an ethylene glycol-mediated process and titanate sheets synthesized using
      the hydrothermal process were used as the template and the precursor,
      respectively, and ii) the template was directly removed in the reaction without
      posttreatment. Furthermore, a possible mechanism was proposed for the formation
      of tubular structures.

PMID- 16813435
TI  - Ferrocenyl compound as a multiresponsive calcium chemosensor with remarkable
      fluorescence properties in CH3CN.
AB  - We have synthesized a novel disubstituted ferrocenyl compound
      [Fe(C5H4CO(CH=CH)2C6H4NEt2)2] (3) that displays a remarkable fluorescence quantum
      yield (1.1 x 10(-1)) in acetonitrile, and we have studied its capacity for
      calcium detection in depth using both electrochemical and optical techniques in
      this medium. The results of our NMR analysis reveal that the ligand-calcium
      interaction is CO-centered and that an uncommon equilibrium occurs between 3 and
      calcium triflate, involving five species of different stoichiometries. In
      contrast, our analysis of the UV-vis absorption data indicates that only three
      species of different stoichiometries are formed when calcium perchlorate is used
      with 3. Mass spectrometry measurements provide strong support for the formation
      of all these different species in solution. In addition, the electrochemical
      detection of calcium triflate by 3 leads to an irreversible Fe(II)/Fe(III)
      oxidation process with an unusual negative shift (-60 mV) caused by the
      (n)Bu4NBF4 salt effect on the Ca2+-3 interaction process. Compound 3 can also be
      an original optical probe to detect calcium perchlorate over a wide range of salt
      concentration by UV-vis absorption spectroscopy. The most original and intriguing
      property of compound 3 is that it exhibits an unprecedented "multistep"
      fluorescence behavior upon addition of this salt.

PMID- 16813436
TI  - Insights into the mechanism of selective olefin epoxidation catalyzed by [gamma
      (SiO4)W10O32H4]4-. A computational study.
AB  - A mechanism for the H2O2-based epoxidation of olefins catalyzed by the lacunary
      polyoxometalate (POM) [gamma-(SiO4)W10O32H4]4- (1) has been investigated at the
      DFT level. In this study, for the first time a "hydroperoxy" mechanism for this
      important process has been proposed. It is divided into two steps and
      investigated using the whole lacunary compound as a model. In the first step, a
      hydroperoxy (W-OOH) species and a water molecule are generated. The formation of
      this nonradical oxidant (W-OOH), consistent with the experimental suggestions,
      occurs with a barrier of 4.4 (7.2) kcal/mol (the number without parenthesis
      includes solvent effects in benzene, while the one with parenthesis is in the gas
      phase). In the second step, the O-O bond of the W-OOH species is cleaved, and an
      epoxide is formed. This step has a barrier of 38.7 (40.0) kcal/mol. It was found
      that the presence of one and two (CH3)4N+ countercations significantly reduces
      the rate-limiting barrier by 7.6 (8.3) and 11.9 (12.6) kcal/mol, respectively,
      and makes this lacunary POM a very efficient catalyst for epoxidation of olefins
      by hydrogen peroxide. It was demonstrated that the lacunary polyoxometalate
      basically acts as a mononuclear W(VI) complex in activating the oxidant, a
      conceptually noteworthy finding.

PMID- 16813438
TI  - The effect of damage on the viscoelastic behavior of human vertebral trabecular
      bone.
AB  - The present study examines the viscoelastic behavior of cancellous bone at low
      strains and the effects of damage on this viscoelastic behavior. It provides
      experimental evidence of interaction between stress relaxation behavior and the
      effect of accumulated damage. The results suggest that damage is at least
      orthotropic in trabecular bone specimens under uniaxial loading. Simple linear
      models of viscoelasticity described the time-dependent stress-strain behavior at
      low strains before and after specimen damage, although better fits of these
      models were obtained prior to damage. Modeling the observed changes in relaxation
      times with damage accumulation appears necessary to successfully predict the post
      damage viscoelastic response.

PMID- 16813439
TI  - Comparison of cervical disk implants and cervical disk fusion treatments in human
      cadaveric models.
AB  - Articulating cervical disk implants have been proposed as an alternative to disk
      fusion in the treatment of cervical disk disease. To examine the mechanical
      effect of articulating cervical disk implants (ACDI) versus simulated cervical
      disk fusion, a mechanical test device was constructed and cadaveric tests were
      carried out. While results show little effect on the pressures above and below
      the treatment level, the percent hysteretic behavior of the specimens trended to
      be higher for the ACDI, indicating that these implants retain more of the natural
      energy absorption capability of the cervical spine.

PMID- 16813440
TI  - Frequency response of a viscoelastic tensegrity model: Structural rearrangement
      contribution to cell dynamics.
AB  - In an attempt to understand the role of structural rearrangement onto the cell
      response during imposed cyclic stresses, we simulated numerically the frequency
      dependent behavior of a viscoelastic tensegrity structure (VTS model) made of 24
      elastic cables and 6 rigid bars. The VTS computational model was based on the
      nonsmooth contact dynamics (NSCD) method in which the constitutive elements of
      the tensegrity structure are considered as a set of material points that mutually
      interact. Low amplitude oscillatory loading conditions were applied and the
      frequency response of the overall structure was studied in terms of frequency
      dependence of mechanical properties. The latter were normalized by the
      homogeneous properties of constitutive elements in order to capture the essential
      feature of spatial rearrangement. The results reveal a specific frequency
      dependent contribution of elastic and viscous effects which is responsible for
      significant changes in the VTS model dynamical properties. The mechanism behind
      is related to the variable contribution of spatial rearrangement of VTS elements
      which is decreased from low to high frequency as dominant effects are transferred
      from mainly elastic to mainly viscous. More precisely, the elasticity modulus
      increases with frequency while the viscosity modulus decreases, each evolution
      corresponding to a specific power-law dependency. The satisfactorily agreement
      found between present numerical results and the literature data issued from in
      vitro cell experiments suggests that the frequency-dependent mechanism of spatial
      rearrangement presently described could play a significant and predictable role
      during oscillatory cell dynamics.

PMID- 16813441
TI  - Mathematical modeling of the biomechanics of the lamina cribrosa under elevated
      intraocular pressures.
AB  - Comprehensive understanding of the biomechanical performance of the lamina
      cribrosa (LC) and the optic nerve head is central to understanding the role of
      elevated intraocular pressures (IOP) in chronic open angle glaucoma. In this
      paper, six closed-from mathematical models based on different idealizations of
      the LC are developed and compared. This approach is used to create further
      understanding of the biomechanical behavior by identifying the LC features and
      properties that have a significant effect on its performance under elevated IOP.
      The models developed are based on thin circular plate and membrane theories, and
      consider influences such as in-plane pretension caused by scleral expansion and
      large deflections. Comparing the results of the six models against a full ocular
      globe finite element model suggests the significance of the in-plane pretension
      and the importance of assuming that the sclera provides the LC with a clamped
      edge. The model that provided the most accurate representation of the finite
      element model was also used to predict the behavior of a number of LC
      experimental tests presented in the literature. In addition to the deflections
      under elevated IOP, the model predictions include the distributions of stress and
      strain, which are shown to be compatible with the progression of visual field
      loss experienced in glaucoma.

PMID- 16813442
TI  - Experimental validation of an inverse heat transfer algorithm for optimizing
      hyperthermia treatments.
AB  - Hyperthermia is a cancer treatment modality in which body tissue is exposed to
      elevated temperatures to destroy cancerous cells. Hyperthermia treatment planning
      refers to the use of computational models to optimize the heating protocol with
      the goal of isolating thermal damage to predetermined treatment areas. This paper
      presents an algorithm to optimize a hyperthermia treatment protocol using the
      conjugate gradient method with the adjoint problem. The output of the
      minimization algorithm is a heating protocol that will cause a desired amount of
      thermal damage. The transient temperature distribution in a cylindrical region is
      simulated using the bioheat transfer equation. Temperature and time are
      integrated to calculate the extent of thermal damage in the region via a first
      order rate process based on the Arrhenius equation. Several validation
      experiments are carried out by applying the results of the minimization algorithm
      to an albumen tissue phantom. Comparisons of metrics describing the damage region
      (the height and radius of the volume of thermally ablated phantom) show good
      agreement between the desired extent of damage and the measured extent of damage.
      The sensitivity of the bioheat transfer model and the Arrhenius damage model to
      their constituent parameters is calculated to create a tolerable range of error
      between the desired and measured extent of damage. The measured height and radius
      of the ablated region fit well within the tolerable range of error found in the
      sensitivity analysis.

PMID- 16813443
TI  - Blood flow dynamics in saccular aneurysm models of the basilar artery.
AB  - Blood flow dynamics under physiologically realistic pulsatile conditions plays an
      important role in the growth, rupture, and surgical treatment of intracranial
      aneurysms. The temporal and spatial variations of wall pressure and wall shear
      stress in the aneurysm are hypothesized to be correlated with its continuous
      expansion and eventual rupture. In addition, the assessment of the velocity field
      in the aneurysm dome and neck is important for the correct placement of
      endovascular coils. This paper describes the flow dynamics in two representative
      models of a terminal aneurysm of the basilar artery under Newtonian and non
      Newtonian fluid assumptions, and compares their hemodynamics with that of a
      healthy basilar artery. Virtual aneurysm models are investigated numerically,
      with geometric features defined by beta = 0 deg and beta = 23.2 deg, where beta
      is the tilt angle of the aneurysm dome with respect to the basilar artery. The
      intra-aneurysmal pulsatile flow shows complex ring vortex structures for beta = 0
      deg and single recirculation regions for beta = 23.2 deg during both systole and
      diastole. The pressure and shear stress on the aneurysm wall exhibit large
      temporal and spatial variations for both models. When compared to a non-Newtonian
      fluid, the symmetric aneurysm model (beta = 0 deg) exhibits a more unstable
      Newtonian flow dynamics, although with a lower peak wall shear stress than the
      asymmetric model (beta = 23.2 deg). The non-Newtonian fluid assumption yields
      more stable flows than a Newtonian fluid, for the same inlet flow rate. Both
      fluid modeling assumptions, however, lead to asymmetric oscillatory flows inside
      the aneurysm dome.

PMID- 16813444
TI  - The effect of vortex formation on left ventricular filling and mitral valve
      efficiency.
AB  - A new mechanism for quantifying the filling energetics in the left ventricle (LV)
      and past mechanical heart valves (MHV) is identified and presented. This
      mechanism is attributed to vortex formation dynamics past MHV leaflets. Recent
      studies support the conjecture that the natural healthy left ventricle (LV)
      performs in an optimum, energy-preserving manner by redirecting the flow with
      high efficiency. Yet to date, no quantitative proof has been presented. The
      present work provides quantitative results and validation of a theory based on
      the dynamics of vortex ring formation, which is governed by a critical formation
      number (FN) that corresponds to the dimensionless time at which the vortex ring
      has reached its maximum circulation content, in support of this hypothesis.
      Herein, several parameters (vortex ring circulation, vortex ring energy, critical
      FN, hydrodynamic efficiencies, vortex ring propagation speed) have been
      quantified and presented as a means of bridging the physics of vortex formation
      in the LV. In fact, the diastolic hydrodynamic efficiencies were found to be 60,
      41, and 29%, respectively, for the porcine, anti-anatomical, and anatomical valve
      configurations. This assessment provides quantitative proof of vortex formation,
      which is dependent of valve design and orientation, being an important flow
      characteristic and associated to LV energetics. Time resolved digital particle
      image velocimetry with kilohertz sampling rate was used to study the ejection of
      fluid into the LV and resolve the spatiotemporal evolution of the flow. The
      clinical significance of this study is quantifying vortex formation and the
      critical FN that can potentially serve as a parameter to quantify the LV filling
      process and the performance of heart valves.

PMID- 16813445
TI  - Squeezing flows of vaginal gel formulations relevant to microbicide drug
      delivery.
AB  - Efficacy of topical microbicidal drug delivery formulations against HIV depends
      in part on their ability to coat, distribute, and be retained on epithelium. Once
      applied to the vagina, a formulation is distributed by physical forces including:
      gravity, surface tension, shearing, and normal forces from surrounding tissues,
      i.e., squeezing forces. The present study focused on vaginal microbicide
      distribution due to squeezing forces. Mathematical simulations of squeezing flows
      were compared with squeezing experiments, using model vaginal gel formulations.
      Our objectives were: (1) to determine if mathematical simulations can accurately
      describe squeezing flows of vaginal gel formulations; (2) to find the best model
      and optimized parameter sets to describe these gels; and (3) to examine vaginal
      coating due to squeezing using the best models and summary parameters for each
      gel. Squeezing flow experiments revealed large differences in spreadability
      between formulations, suggesting different coating distributions in vivo. We
      determined the best squeezing flow models and summary parameters for six test
      gels of two compositions, cellulose and polyacrylic acid (PAA). We found that for
      some gels it was preferable to deduce model input parameters directly from
      squeezing flow experiments. For the cellulose gels, slip conditions in squeezing
      flow experiments needed to be evaluated. For PAA gels, we found that in the
      absence of squeezing experiments, rotational viscometry measurements (to
      determine Herschel-Bulkley parameters) led to reasonably accurate predictions of
      squeezing flows. Results indicated that yield stresses may be a strong
      determinant of squeezing flow mechanics. This study serves as a template for
      further investigations of other gels and determination of which sources of
      rheological data best characterize potential microbicidal formulations. These
      mathematical simulations can serve as useful tools for exploring drug delivery
      parameters, and optimizing formulations, prior to costly clinical trials.

PMID- 16813446
TI  - Microbubble expansion in a flexible tube.
AB  - We have utilized a computational model of the expansion of a microbubble in a
      liquid-filled flexible tube to investigate the potential for acoustic
      vaporization of perfluorocarbon droplets to damage blood vessels during a novel
      gas embolotherapy technique for the potential treatment of tumors. This model
      uses a fixed grid, multi-domain, interface tracking, direct numerical simulation
      method that treats all interfaces and boundaries as sharp discontinuities for
      high accuracy. In the current work, we examined effects of initial bubble size on
      the flows and wall stresses that result from droplet vaporization. The remaining
      dimensionless parameters that govern the system response (Reynolds, Weber, and
      Strouhal numbers, initial bubble pressure, and wall stiffness and tension) were
      selected to model an arteriole. The results for a flexible tube are significantly
      different from those for a rigid tube. Two major flow regimes occur due to the
      combined effect of bubble and tube deformation: in flow at the tube ends and out
      flow near the bubble surface. The flexibility of the tube largely dissipates the
      extreme pressure that develops in the rigid tube model. Both the magnitude and
      the overall expansion time of the rapidly changing pressure are greatly reduced
      in the flexible tube. Smaller initial bubble diameters, relative to the vessel
      diameter, result in lower wall stresses. This study indicates that wall
      flexibility can significantly influence the wall stresses that result from
      acoustic vaporization of intravascular perfluorocarbon droplets, and suggests
      that acoustic activation of droplets in larger, more flexible vessels may be less
      likely to damage or rupture vessels than activation in smaller and stiffer
      vessels.

PMID- 16813448
TI  - Finite-Reynolds-number effects in steady, three-dimensional airway reopening.
AB  - Motivated by the physiological problem of pulmonary airway reopening, we study
      the steady propagation of an air finger into a buckled elastic tube, initially
      filled with viscous fluid. The system is modeled using geometrically non-linear,
      Kirchhoff-Love shell theory, coupled to the free-surface Navier-Stokes equations.
      The resulting three-dimensional, fluid-structure-interaction problem is solved
      numerically by a fully coupled finite element method. Our study focuses on the
      effects of fluid inertia, which has been neglected in most previous studies. The
      importance of inertial forces is characterized by the ratio of the Reynolds and
      capillary numbers, ReCa, a material parameter. Fluid inertia has a significant
      effect on the system's behavior, even at relatively small values of ReCa. In
      particular, compared to the case of zero Reynolds number, fluid inertia causes a
      significant increase in the pressure required to drive the air finger at a given
      speed.

PMID- 16813447
TI  - Simulations of congenital septal defect closure and reactivity testing in patient
      specific models of the pediatric pulmonary vasculature: A 3D numerical study with
      fluid-structure interaction.
AB  - Clinical imaging methods are highly effective in the diagnosis of vascular
      pathologies, but they do not currently provide enough detail to shed light on the
      cause or progression of such diseases, and would be hard pressed to foresee the
      outcome of surgical interventions. Greater detail of and prediction capabilities
      for vascular hemodynamics and arterial mechanics are obtained here through the
      coupling of clinical imaging methods with computational techniques. Three
      dimensional, patient-specific geometric reconstructions of the pediatric proximal
      pulmonary vasculature were obtained from x-ray angiogram images and meshed for
      use with commercial computational software. Two such models from hypertensive
      patients, one with multiple septal defects, the other who underwent vascular
      reactivity testing, were each completed with two sets of suitable fluid and
      structural initial and boundary conditions and used to obtain detailed transient
      simulations of artery wall motion and hemodynamics in both clinically measured
      and predicted configurations. The simulation of septal defect closure, in which
      input flow and proximal vascular stiffness were decreased, exhibited substantial
      decreases in proximal velocity, wall shear stress (WSS), and pressure in the post
      op state. The simulation of vascular reactivity, in which distal vascular
      resistance and proximal vascular stiffness were decreased, displayed negligible
      changes in velocity and WSS but a significant drop in proximal pressure in the
      reactive state. This new patient-specific technique provides much greater detail
      regarding the function of the pulmonary circuit than can be obtained with current
      medical imaging methods alone, and holds promise for enabling surgical planning.

PMID- 16813449
TI  - Simulation of physiological loading in total hip replacements.
AB  - The determination of biomechanical force systems of implanted femurs to obtain
      adequate strain measurements has been neglected in many published studies. Due to
      geometric alterations induced by surgery and those inherent to the design of the
      prosthesis, the loading system changes because the lever arms are modified. This
      paper discusses the determination of adequate loading of the implanted femur
      based on the intact femur-loading configuration. Four reconstructions with
      Lubinus SPII, Charnley Roundback, Muller Straight and Stanmore prostheses were
      used in the study. Pseudophysiologic and nonphysiologic implanted system forces
      were generated and assessed with finite element analysis. Using an equilibrium
      system of forces composed by the Fx (medially direction) component of the hip
      contact force and the bending moments Mx (median plane) and My (coronal plane)
      allowed adequate, pseudo-physiological loading of the implanted femur. We suggest
      that at least the bending moment at the coronal plane must be restored in the
      implanted femur-loading configuration.

PMID- 16813450
TI  - An optimized image matching method for determining in-vivo TKA kinematics with a
      dual-orthogonal fluoroscopic imaging system.
AB  - This study presents an optimized matching algorithm for a dual-orthogonal
      fluoroscopic image system used to determine six degrees-of-freedom total knee
      arthroplasty (TKA) kinematics in-vivo. The algorithm was evaluated using
      controlled conditions and standard geometries. Results of the validation
      demonstrate the algorithm's robustness and capability of realizing a pose from a
      variety of initial poses. Under idealized conditions, poses of a TKA system were
      recreated to within 0.02+/-0.01 mm and 0.02+/-0.03 deg for the femoral component
      and 0.07+/-0.09 mm and 0.16+/-0.18 deg for the tibial component. By employing a
      standardized geometry with spheres, the translational accuracy and repeatability
      under actual conditions was found to be 0.01+/-0.06 mm. Application of the
      optimized matching algorithm to a TKA patient showed that the pose of in-vivo TKA
      components can be repeatedly located, with standard deviations less than +/-0.12
      mm and +/-0.12 deg for the femoral component and +/-0.29 mm and +/-0.25 deg for
      the tibial component. This methodology presents a useful tool that can be readily
      applied to the investigation of in-vivo motion of TKA kinematics.

PMID- 16813451
TI  - In vitro assessment of a motion-based optimization method for locating the
      talocrural and subtalar joint axes.
AB  - The locations of the joint axes of the ankle complex vary considerably between
      subjects, yet no noninvasive method with demonstrated accuracy exists for
      locating these axes. The moments of muscle and ground reaction forces about the
      joint axes are dependent on axis locations, making knowledge of these locations
      critical to accurate musculoskeletal modeling of the foot and ankle. The accuracy
      of a computational optimization method that fits a two-revolute model to measured
      motion was assessed using computer-generated data, a two-revolute mechanical
      linkage, and three lower-leg cadaver specimens. Motions were applied to cadaver
      specimens under axial load while bone-mounted markers attached to the tibia,
      talus, and calcaneus were tracked using a video-based motion analysis system.
      Estimates of the talocrural and subtalar axis locations were computed from
      motions of the calcaneus relative to the tibia using the optimization method.
      These axes were compared to mean helical axes computed directly from tibia,
      talus, and calcaneus motions. The optimization method performed well when the
      motions were computer-generated or measured in the mechanical linkage, with
      angular differences between optimization and mean helical axes ranging from 1 deg
      to 5 deg. In the cadaver specimens, however, these differences exceeded 20 deg.
      Optimization methods that locate the anatomical joint axes of the ankle complex
      by fitting two revolute joints to measured tibia-calcaneus motions may be limited
      because of problems arising from non-revolute behavior.

PMID- 16813452
TI  - Validation of a new model-based tracking technique for measuring three
      dimensional, in vivo glenohumeral joint kinematics.
AB  - Shoulder motion is complex and significant research efforts have focused on
      measuring glenohumeral joint motion. Unfortunately, conventional motion
      measurement techniques are unable to measure glenohumeral joint kinematics during
      dynamic shoulder motion to clinically significant levels of accuracy. The purpose
      of this study was to validate the accuracy of a new model-based tracking
      technique for measuring three-dimensional, in vivo glenohumeral joint kinematics.
      We have developed a model-based tracking technique for accurately measuring in
      vivo joint motion from biplane radiographic images that tracks the position of
      bones based on their three-dimensional shape and texture. To validate this
      technique, we implanted tantalum beads into the humerus and scapula of both
      shoulders from three cadaver specimens and then recorded biplane radiographic
      images of the shoulder while manually moving each specimen's arm. The position of
      the humerus and scapula were measured using the model-based tracking system and
      with a previously validated dynamic radiostereometric analysis (RSA) technique.
      Accuracy was reported in terms of measurement bias, measurement precision, and
      overall dynamic accuracy by comparing the model-based tracking results to the
      dynamic RSA results. The model-based tracking technique produced results that
      were in excellent agreement with the RSA technique. Measurement bias ranged from 
      0.126 to 0.199 mm for the scapula and ranged from -0.022 to 0.079 mm for the
      humerus. Dynamic measurement precision was better than 0.130 mm for the scapula
      and 0.095 mm for the humerus. Overall dynamic accuracy indicated that rms errors
      in any one direction were less than 0.385 mm for the scapula and less than 0.374
      mm for the humerus. These errors correspond to rotational inaccuracies of
      approximately 0.25 deg for the scapula and 0.47 deg for the humerus. This new
      model-based tracking approach represents a non-invasive technique for accurately
      measuring dynamic glenohumeral joint motion under in vivo conditions. The model
      based technique achieves accuracy levels that far surpass all previously reported
      non-invasive techniques for measuring in vivo glenohumeral joint motion. This
      technique is supported by a rigorous validation study that provides a realistic
      simulation of in vivo conditions and we fully expect to achieve these levels of
      accuracy with in vivo human testing. Future research will use this technique to
      analyze shoulder motion under a variety of testing conditions and to investigate
      the effects of conservative and surgical treatment of rotator cuff tears on
      dynamic joint stability.

PMID- 16813453
TI  - A structural model for the flexural mechanics of nonwoven tissue engineering
      scaffolds.
AB  - The development of methods to predict the strength and stiffness of biomaterials
      used in tissue engineering is critical for load-bearing applications in which the
      essential functional requirements are primarily mechanical. We previously
      quantified changes in the effective stiffness (E) of needled nonwoven
      polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) scaffolds due to tissue
      formation and scaffold degradation under three-point bending. Toward predicting
      these changes, we present a structural model for E of a needled nonwoven scaffold
      in flexure. The model accounted for the number and orientation of fibers within a
      representative volume element of the scaffold demarcated by the needling process.
      The spring-like effective stiffness of the curved fibers was calculated using the
      sinusoidal fiber shapes. Structural and mechanical properties of PGA and PLLA
      fibers and PGA, PLLA, and 50:50 PGA/PLLA scaffolds were measured and compared
      with model predictions. To verify the general predictive capability, the
      predicted dependence of E on fiber diameter was compared with experimental
      measurements. Needled nonwoven scaffolds were found to exhibit distinct preferred
      (PD) and cross-preferred (XD) fiber directions, with an E ratio (PD/XD) of
      approximately 3:1. The good agreement between the predicted and experimental
      dependence of E on fiber diameter (R2 = 0.987) suggests that the structural model
      can be used to design scaffolds with E values more similar to native soft
      tissues. A comparison with previous results for cell-seeded scaffolds (Engelmayr,
      G. C., Jr., et al., 2005, Biomaterials, 26(2), pp. 175-187) suggests, for the
      first time, that the primary mechanical effect of collagen deposition is an
      increase in the number of fiber-fiber bond points yielding effectively stiffer
      scaffold fibers. This finding indicated that the effects of tissue deposition on
      needled nonwoven scaffold mechanics do not follow a rule-of-mixtures behavior.
      These important results underscore the need for structural approaches in modeling
      the effects of engineered tissue formation on nonwoven scaffolds, and their
      potential utility in scaffold design.

PMID- 16813454
TI  - Dynamic response of immature bovine articular cartilage in tension and
      compression, and nonlinear viscoelastic modeling of the tensile response.
AB  - Very limited information is currently available on the constitutive modeling of
      the tensile response of articular cartilage and its dynamic modulus at various
      loading frequencies. The objectives of this study were to (1) formulate and
      experimentally validate a constitutive model for the intrinsic viscoelasticity of
      cartilage in tension, (2) confirm the hypothesis that energy dissipation in
      tension is less than in compression at various loading frequencies, and (3) test
      the hypothesis that the dynamic modulus of cartilage in unconfined compression is
      dependent upon the dynamic tensile modulus. Experiment 1: Immature bovine
      articular cartilage samples were tested in tensile stress relaxation and cyclical
      loading. A proposed reduced relaxation function was fitted to the stress
      relaxation response and the resulting material coefficients were used to predict
      the response to cyclical loading. Adjoining tissue samples were tested in
      unconfined compression stress relaxation and cyclical loading. Experiment 2:
      Tensile stress relaxation experiments were performed at varying strains to
      explore the strain-dependence of the viscoelastic response. The proposed
      relaxation function successfully fit the experimental tensile stress-relaxation
      response, with R2 = 0.970+/-0.019 at 1% strain and R2 = 0.992+/-0.007 at 2%
      strain. The predicted cyclical response agreed well with experimental
      measurements, particularly for the dynamic modulus at various frequencies. The
      relaxation function, measured from 2% to 10% strain, was found to be strain
      dependent, indicating that cartilage is nonlinearly viscoelastic in tension.
      Under dynamic loading, the tensile modulus at 10 Hz was approximately 2.3 times
      the value of the equilibrium modulus. In contrast, the dynamic stiffening ratio
      in unconfined compression was approximately 24. The energy dissipation in tension
      was found to be significantly smaller than in compression (dynamic phase angle of
      16.7+/-7.4 deg versus 53.5+/-12.8 deg at 10(-3) Hz). A very strong linear
      correlation was observed between the dynamic tensile and dynamic compressive
      moduli at various frequencies (R2 = 0.908+/-0.100). The tensile response of
      cartilage is nonlinearly viscoelastic, with the relaxation response varying with
      strain. A proposed constitutive relation for the tensile response was
      successfully validated. The frequency response of the tensile modulus of
      cartilage was reported for the first time. Results emphasize that fluid-flow
      dependent viscoelasticity dominates the compressive response of cartilage,
      whereas intrinsic solid matrix viscoelasticity dominates the tensile response.
      Yet the dynamic compressive modulus of cartilage is critically dependent upon
      elevated values of the dynamic tensile modulus.

PMID- 16813455
TI  - Comparative in vitro study of bileaflet and tilting disk valve behavior in the
      pulmonary position.
AB  - A study of mechanical heart valve behavior in the pulmonary position as a
      function of pulmonary vascular resistance is reported for the St. Jude Medical
      bileaflet (SJMB) valve and the MedicalCV Omnicarbon (OTD) tilting disk valve.
      Tests were conducted in a pulmonic mock circulatory system and impedance was
      varied in terms of system pulmonary vascular resistance (PVR). An impedance
      spectrum was found using instantaneous pulmonary artery pressure and flow rate
      curves. Both valves fully opened and closed at and above a nominal PVR of 3.0
      mmHg/L/min. The SJMB valve was prone to leaflet bounce at closure, but otherwise
      completely closed, at settings above and below this nominal setting. At PVR
      values at and below 2.0 mmHg/L/min, the SJMB valve exhibited two types of leaflet
      aberrant behavior: single leaflet only closure while the other leaflet fluttered,
      and incomplete closure where both leaflets flutter but neither remain fully
      closed. The OTD valve fully opened and closed to a PVR value of 1.6 mmHg/L/min.
      At lower values, the valve did not close. Valves designed for the left heart can
      show aberrant behavior under normal conditions as pulmonary valves.

PMID- 16813456
TI  - Oxidation of A2E results in the formation of highly reactive aldehydes and
      ketones.
AB  - It has been reported that the photo-oxidation of A2E, a component of human
      retinal lipofuscin, leads to products that are toxic to cells via dark reactions.
      Because these compounds have been implicated in the development of various
      maculopathies such as age-related macular degeneration (AMD), it is important to
      determine the structures of those deleterious compounds. Both the photo-oxidation
      and auto-oxidation of A2E lead to the same complex mixture of products, some of
      which have lower molecular weights than the staring material. Because A2E is
      homologous to beta-carotene, it was hypothesized that its oxidation would lead to
      products analogous to those found in oxidized beta-carotene, namely, a series of
      cleavage products along the acyclic chain with the concomitant formation of
      aldehydes. This was found to be the case based upon 1) the formation of all of
      the aldehydes predicted from the oxidation of beta-carotene, 2) the loss of 28
      amu (carbonyl moiety) from the molecular ion, 3) the facile reaction of the
      aldehydes with nitrophenylhydrazines to form nitrophenylhydrazones and 4) the
      subsequent MS/MS cleavage of those derivatives at the N-N bond. If formed in
      vivo, these aldehydes would have toxic effects on any cell. Finally, the
      similarity in product mixtures from both the photo-oxidation and auto-oxidation
      strongly suggests that the intermolecular photo-oxidation of A2E results
      primarily from a radical process without the involvement of singlet oxygen. Any
      formation of singlet oxygen most likely arises from sensitization by the aldehyde
      oxidation products, as this process is well known for aldehydes, in general, and
      retinal, specifically.

PMID- 16813457
TI  - Photochemical nucleophile mapping: identification of Tyr311 within the catalytic
      domain of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase.
AB  - Photochemical mapping of nucleophiles in close proximity to the active site
      Cys149 of rabbit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was
      demonstrated based on the nucleophilic aromatic photosubstitution reaction using
      two regioisomers of alkoxy-fluoro-nitro-substituted benzenes. Two photophores
      were covalently attached to the active site SH group of GAPDH and the protein was
      subjected to photolysis then to the cyanogen bromide cleavage reaction. The
      advantage of this method is the capability to chase labeled products by
      monitoring absorption at 380 nm because of the chromogenic property of
      photophore. HPLC separation identified a large labeled peptide fragment that was
      further digested by V8 protease for Edman sequence analysis. From the recent X
      ray crystallography of rabbit GAPDH, Tyr311, His176, Ser238 and Lys183 are
      closely located to catalytic Cys149. Among these nucleophiles, Tyr311 was
      preferentially labeled with 2-fluoro-4-nitrophenoxy photophore and no label was
      identified with the isomeric 4-fluoro-2-nitrophenoxy photophore. The result
      clearly reflects the distance between Cys149 and nucleophiles to distinguish the
      nearest Tyr311. As photophores show great reactivity even with water under
      neutral conditions, the distance between nucleophiles and photophores is
      important for photoinduced nucleophilic aromatic substitution. The method will
      provide a useful technique to survey nucleophiles within the catalytic domain.

PMID- 16813458
TI  - Pulmonary intra-alveolar siderophages in SIDS and suffocation: a San Diego
      SIDS/SUDC Research Project report.
AB  - Pulmonary intra-alveolar siderophages (PS) have been suggested as a marker of
      previous attempts at imposed suffocation in infants dying suddenly and
      unexpectedly. The aims of this study were to (1) compare PS counts between cases
      of sudden infant death syndrome (SIDS) and a control group comprised of infants
      whose deaths were attributed to accidental or inflicted suffocation, (2) compare
      clinical variables in SIDS and control suffocation cases, and (3) review
      individual cases irrespective of the cause and manner of death with an average PS
      count greater than 200 per 20 high-power fields (hpf) per lung lobe.
      Retrospective assessment of siderophages in available iron-stained lung sections
      was undertaken in 91 SIDS cases and 29 cases of death due to suffocation (27
      accidents and 2 homicides) from the San Diego SIDS and Sudden Unexplained Death
      in Childhood (SUDC) Research Project (SDSSRP) database. Neither the means of the
      log-transformed PS counts nor the medians of the raw PS counts were significantly
      different between the SIDS and control suffocation groups. The distributions of
      the PS data were different, however-the range was wider in the SIDS group. Only
      6% of each group had a history of prior apparent life-threatening events.
      Approximately three fourths of the families from both groups had no prior
      referral to Child Protective Services. The number of PS varies widely in cases of
      sudden infant death caused by SIDS and accidental or inflicted suffocation and
      cannot be used as an independent variable to ascertain past attempts at
      suffocation.

PMID- 16813459
TI  - Natural remedies for Herpes simplex.
AB  - Herpes simplex is a common viral infection of the skin or mucous membranes. The
      lesions caused by this infection are often painful, burning, or pruritic, and
      tend to recur in most patients. Short-term treatment with acyclovir can
      accelerate the healing of an acute outbreak, and continuous acyclovir therapy is
      often prescribed for people with frequent recurrences. While this drug can reduce
      the recurrence rate by 60-90 percent, it can also cause a wide array of side
      effects, including renal failure, hepatitis, and anaphylaxis. Safe and effective
      alternatives are therefore needed. There is evidence that certain dietary
      modifications and natural substances may be useful for treating active Herpes
      simplex lesions or preventing recurrences. Treatments discussed include lysine,
      vitamin C, zinc, vitamin E, adenosine monophosphate, and lemon balm (Melissa
      officinalis).

PMID- 16813460
TI  - Herpes zoster and postherpetic neuralgia: diagnosis and therapeutic
      considerations.
AB  - Herpes zoster (HZ), also known as shingles, is a painful vesicular rash resulting
      from reactivation of the virus that also causes chickenpox - Varicella zoster
      virus (VZV). Typically, the rash runs its course in a matter of 4-5 weeks. The
      pain, however, may persist months, even years, after the skin heals. This
      phenomenon is known as postherpetic neuralgia (PHN). Often described as an
      intense burning, itching sensation, this pain can be significant to the point of
      being debilitating, and as such can greatly affect quality of life. Although
      shingles is generally regarded as a self-limited condition, the fact it can take
      several weeks to resolve and has the potential for development of complications
      such as PHN presents a challenge to clinicians. Many treatment options are
      available, each offering variable levels of efficacy. Conventional therapies
      include prescription antivirals, corticosteroids, and analgesics, both oral and
      topical. Other considerations include use of over-the-counter anti-inflammatory
      agents, physiotherapy, and nerve block injections. This article reviews herpes
      zoster and postherpetic neuralgia, and presents the most effective conventional
      treatment options currently available, as well as select botanical, nutritional,
      and other considerations that may be beneficial in the management of this
      condition.

PMID- 16813461
TI  - Lead toxicity part II: the role of free radical damage and the use of
      antioxidants in the pathology and treatment of lead toxicity.
AB  - Lead is an environmentally persistent toxin that causes neurological,
      hematological, gastrointestinal, reproductive, circulatory, and immunological
      pathologies. The propensity for lead to catalyze oxidative reactions and generate
      reactive oxygen species has been demonstrated in multiple studies. These reactive
      oxygen species (ROS) inhibit the production of sulfhydryl antioxidants, inhibit
      enzyme reactions impairing heme production, cause inflammation in vascular
      endothelial cells, damage nucleic acids and inhibit DNA repair, and initiate
      lipid peroxidation in cellular membranes. These wide-ranging effects of ROS
      generation have been postulated to be major contributors to lead-exposure related
      disease. Antioxidants - vitamins B6, C and E, zinc, taurine, N-acetylcysteine,
      and alpha-lipoic acid, either alone or in conjunction with standard
      pharmaceutical chelating agents - have been studied in lead-exposed animals. The
      evidence for their use in lead exposure, alone and in conjunction with chelating
      agents, is reviewed in this article.

PMID- 16813462
TI  - Modulation of cytokine expression by traditional medicines: a review of herbal
      immunomodulators.
AB  - Modulation of cytokine secretion may offer novel approaches in the treatment of a
      variety of diseases. One strategy in the modulation of cytokine expression may be
      through the use of herbal medicines. A class of herbal medicines, known as
      immunomodulators, alters the activity of immune function through the dynamic
      regulation of informational molecules such as cytokines. This may offer an
      explanation of the effects of herbs on the immune system and other tissues. For
      this informal review, the authors surveyed the primary literature on medicinal
      plants and their effects on cytokine expression, taking special care to analyze
      research that utilized the multi-component extracts equivalent to or similar to
      what are used in traditional medicine, clinical phytotherapy, or in the
      marketplace. METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify
      research on botanical medicines, in whole or standardized form, that act on
      cytokine activity through different models, i.e., in vivo (human and animal), ex
      vivo, or in vitro. RESULTS: Many medicinal plant extracts had effects on at least
      one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF, and
      IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus
      comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea
      purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala
      tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia,
      Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple
      cytokines. CONCLUSION: The in vitro and in vivo research demonstrates that the
      reviewed botanical medicines modulate the secretion of multiple cytokines. The
      reported therapeutic success of these plants by traditional cultures and modern
      clinicians may be partially due to their effects on cytokines. Phytotherapy
      offers a potential therapeutic modality for the treatment of many differing
      conditions involving cytokines. Given the activity demonstrated by many of the
      reviewed herbal medicines and the increasing awareness of the broad-spectrum
      effects of cytokines on autoimmune conditions and chronic degenerative processes,
      further study of phytotherapy for cytokine-related diseases and syndromes is
      warranted.

PMID- 16813463
TI  - Monograph. Eleutherococcus senticosus.

PMID- 16813464
TI  - Molybdenum. Monograph.

PMID- 16813465
TI  - The Redelberger antigen: a family study, a family story.
AB  - The Redelberger antigen (Rba) was first discovered in 1974 on the RBCs of a blood
      donor who was an employee of the Community Blood Center in Dayton, Ohio. The
      discovery was made as a result of the investigation of a reagent contamination
      problem. Two examples of the Rba antigen were subsequently identified in the
      United Kingdom,but no "new"examples have been identified in the United States or
      Europe. Anti-Rba is a commonly occurring antibody, often found in combination
      with other antibody specificities, especially in combination with other
      antibodies to low-incidence antigens.

PMID- 16813466
TI  - Review: monoclonal reagents and detection of unusual or rare phenotypes or
      antibodies.
AB  - Monoclonal antibodies have been used in the formulation of commercially available
      blood grouping reagents since the early 1990s. It became apparent early on that
      introducing them into routine use along with, or instead of, human- or animal
      derived reagents could and did lead to discrepant reactions. These discrepancies
      most often came to light when confirming a blood type obtained previously with
      human- or animal-source reagents or when using two or more sources of a reagent
      from the same or another manufacturer to perform blood typing or antibody
      detection or identification testing. A number of factors contribute to
      differences in reactivity of reagents that are of the same specificity but are
      from more than one source. One factor is the use of different clones of the same
      specificity to manufacture blood bank reagents. Another is the effect of the
      various diluents used by different manufacturers to formulate reagents that
      contain the same clone(s). In addition, RBCs having unusual or rare phenotypes
      can cause discrepant reactions when performing phenotyping. Discrepant reactions
      can also occur because of patient or donor antibodies that react in an unusual
      manner when antiglobulin tests are performed with monoclonal antihuman globulin
      (AHG) versus rabbit AHG reagent. It is important to know the identity of the
      unusual or rare phenotypes and antibodies and to be able to recognize the
      different types of reactions that will be observed when using more than one
      reagent of the same specificity. Most importantly, one must be able to interpret
      reactions correctly and establish the true blood type of the RBCs or specificity
      of the antibodies. This review will describe situations in which the use of
      monoclonal reagents from more than one source or manufacturer, or comparison with
      results of human- and animal-source reagents, resulted in discrepancies with
      unusual or rare phenotypes or antibodies. Many of the samples described in this
      review were sent to the reference laboratory at Gamma Biologicals, Inc., in
      Houston, Texas, which later became ImmucorGamma with sites in Norcross, Georgia,
      and Houston, Texas.

PMID- 16813467
TI  - Rare blood donors: a personal approach.
AB  - The National Blood Group Reference Laboratory (NBGRL) in Israel was established
      in Jerusalem in 1971 and transferred to Magen David Adom (MDA), National Blood
      Services in 1995. This laboratory was the inspiration of the first author of this
      article for over 30 years. The realization of this vision was made possible by
      the cooperation of colleagues and laboratory workers in blood transfusion
      services throughout the country. The aim of the service was to provide diagnostic
      help in resolving immunohematologic problems found in the blood banks and clinics
      in Israel. In the beginning, only a part-time technician performed the work and
      testing was done using very limited reagents. The service was expanded by
      personal visits to all of the 22 blood banks in Israel to explain the aim of this
      new service and to educate them about the importance of resolving each and every
      case. One major issue was the cost involved in referring problems but it was
      decided at the outset that these would be covered by the government to ensure
      that a workup would be performed for all referred cases. The expansion of the
      service could not have been achieved without the help of the SCARF program. This
      voluntary service enabled us to identify the first rare donors in Israel, resolve
      complex cases, and find compatible blood for our patients. To illustrate the
      importance of the NBGRL in Israel and the rapid resolution of cases referred,
      several individual stories are described. The purpose of this review is to show
      the importance of the NBGRL in identifying rare blood groups and in providing and
      coordinating services and the importance of keeping in close contact with the
      rare donors to encourage and promote their donations, which may save lives.

PMID- 16813468
TI  - Case report:DNA testing resolves unusual results in the Dombrock system.
AB  - Typing for antigens in the Dombrock blood group system and identifying the
      corresponding antibodies are notoriously difficult tasks. The reagents are scarce
      and the antibodies are weakly reactive. When RBCs from family members of a
      patient with an antibody to a high-prevalence Dombrock antigen were tested for
      compatibility,an unusual pattern of inheritance was observed:RBCs from the
      patient's children and one niece, in addition to those from some of the patient's
      siblings,were compatible. This prompted the performance of DNA-based assays for
      DO alleles and the results obtained were consistent with and explained the
      compatibility test results. It was possible to study this large kindred because
      of the cooperation of family members, hospital personnel, and reference
      laboratory staff.

PMID- 16813469
TI  - Problems highlighted when using anticoagulated samples in the standard tube low
      ionic strength antiglobulin test.
AB  - Within the UK blood transfusion services, there is currently no recommendation
      for the use of either clotted or anticoagulated samples for antibody
      identification testing. This report describes three cases in which the detection
      of IgM antibodies was impeded by the use of anticoagulated samples. Two patient
      samples, referred for compatibility testing, were both identified as having IgM
      complement-activating anti-S and the remaining case involved an antenatal patient
      with IgM complement-activating anti-Vel. In all three cases, the coincidental
      referral and investigation of both clotted and anticoagulated samples led to the
      discrepancy in serum and plasma test results becoming apparent. Potential errors
      in selection of suitable blood for transfusion and appropriate antenatal
      management were avoided by correct identification of the antibodies present using
      the clotted samples.

PMID- 16813471
TI  - Interpreting systematic reviews: sometimes, more is better.

PMID- 16813472
TI  - Effect of brisk walking in 1 or 2 daily bouts and moderate resistance training on
      lower-extremity muscle strength, balance, and walking performance in women who
      recently went through menopause: a randomized, controlled trial.
AB  - BACKGROUND AND PURPOSE: Menopause may induce a phase of rapid decreases in bone
      mineral density, aerobic fitness, muscle strength, and balance, especially in
      sedentary women. The purpose of this study was to examine the effects and
      feasibility of an exercise program of 1 or 2 bouts of walking and resistance
      training on lower-extremity muscle strength (the force-generating capacity of
      muscle), balance, and walking performance in women who recently went through
      menopause. SUBJECTS AND METHODS: The subjects were 134 women who recently went
      through menopause. The study was a 15-week, randomized, controlled trial with
      continuous and fractionated exercise groups. The outcomes assessed were lower
      extremity muscle strength, balance, and walking time over 2 km. Feasibility was
      assessed by questionnaires, interviews, and training logs. RESULTS: One hundred
      twenty-eight women completed the study. Adherence to the study protocol was 92%.
      Both continuous and fractionated exercise groups improved equally in lower
      extremity muscle strength and walking time but not in balance. Almost 70% of the
      subjects considered the program to be feasible. Two daily walking sessions caused
      fewer lower-extremity problems than did continuous walking. DISCUSSION AND
      CONCLUSION: Brisk walking combined with moderate resistance training is feasible
      and effective. Fractionating the walking into 2 daily sessions is more feasible
      than continuous walking.

PMID- 16813473
TI  - Effects of a multimodal exercise program for people with ankylosing spondylitis.
AB  - BACKGROUND AND PURPOSE: Few randomized controlled studies have examined the
      effects of exercise in patients with ankylosing spondylitis (AS). This study
      investigated the effects of a 12-week, multimodal exercise program in patients
      with AS. SUBJECTS: A convenience sample of 30 patients with AS (18 male, 12
      female), with a mean age of 34.9 years (SD=6.28), participated in the study.
      Twenty-six subjects were classified as having stage I AS and 4 subjects were
      classified as having stage II AS according to the modified New York Criteria.
      METHODS: This study was a randomized controlled trial. Subjects were assigned to
      either a group that received an exercise program or to a control group. The
      exercise program consisted of 50 minutes of multimodal exercise, including
      aerobic, stretching, and pulmonary exercises, 3 times a week for 3 months.
      Subjects in both groups received medical treatment for AS, but the exercise group
      received the exercise program in addition to the medical treatment. All subjects
      received a physical examination at baseline and at 12 weeks. The examinations
      were conducted under the supervision of a physician who specialized in physical
      medicine and rehabilitation and included the assessment of spinal mobility using
      2 methods: clinical measurements (chin-to-chest distance, Modified Schober
      Flexion Test, occiput-to-wall distance, finger-to-floor distance, and chest
      expansion) and inclinometer measurements (gross hip flexion, gross lumbar
      flexion, and gross thoracic flexion). In addition, vital capacity was measured by
      a physiologist, and physical work capacity was evaluated by a doctorally prepared
      exercise instructor. RESULTS: The measurements of the exercise group for chest
      expansion, chin-to-chest distance, Modified Schober Flexion Test, and occiput-to
      wall distance were significantly better than those of the control group after the
      3-month exercise period. The spinal movements of the exercise group improved
      significantly at the end of exercise program, but those of the control group
      showed no significant change. In addition, the results showed that the
      posttraining value of gross thoracic flexion of the exercise group was
      significantly higher than that of the control group. Physical work capacity and
      vital capacity values improved in the exercise group but decreased in the control
      group. DISCUSSION AND CONCLUSION: In this study, a multimodal exercise program
      including aerobic, stretching, and pulmonary exercises provided in conjunction
      with routine medical management yielded greater improvements in spinal mobility,
      work capacity, and chest expansion.

PMID- 16813474
TI  - A simplified stroke rehabilitation assessment of movement instrument.
AB  - BACKGROUND AND PURPOSE: An efficient, reliable, and valid instrument for
      assessing motor function in patients with stroke is needed by both clinicians and
      researchers. To improve administration efficiency, we applied the
      multidimensional Rasch model to the 30-item, 3-subscale Stroke Rehabilitation
      Assessment of Movement (STREAM) instrument to produce a concise, reliable, and
      valid instrument (simplified STREAM [S-STREAM]) for measuring motor function in
      patients with stroke. SUBJECTS AND METHODS: The STREAM (consisting of 3
      subscales: upper-limb movements, lower-limb movements, and mobility) was
      administered to 351 subjects with first stroke occurrence and a median time after
      stroke of 12.5 months. The unidimensionality of each subscale of the STREAM first
      was verified with unidimensional Rasch analysis. Each subscale of the STREAM then
      was simplified by deleting redundant items on the basis of expert opinion and the
      results of the Rasch analysis. The Rasch reliability of the S-STREAM and the
      concurrent validity of the S-STREAM with the STREAM were examined with
      multidimensional Rasch analysis and the intraclass correlation coefficient (ICC),
      respectively. RESULTS: After deleting the items that did not fit the Rasch model,
      we found that the 8-item upper-limb movement subscale, the 9-item lower-limb
      movement subscale, and the 10-item mobility subscale assessed single,
      unidimensional upper-limb movements, lower-limb movements, and mobility,
      respectively. We selected 5 items from each subscale to construct the S-STREAM
      and found that the reliability of each subscale of the resulting simplified
      instrument was high (Rasch reliability coefficients of > or =.91). The agreement
      between the subscale scores (Rasch estimates) of the S-STREAM and those of the
      STREAM was excellent (ICC of > or =.99, with a lower limit for the 95% confidence
      interval of > or =.985), indicating good concurrent validity of the S-STREAM with
      the STREAM. DISCUSSION AND CONCLUSION: The S-STREAM demonstrates high Rasch
      reliability, unidimensionality, and concurrent validity with the STREAM in
      patients with stroke. Furthermore, the S-STREAM is efficient to administer, as it
      consists of only half the number of items in the original STREAM. Additional
      studies to examine other psychometric properties (eg, predictive validity and
      responsiveness) of the S-STREAM or its psychometric properties in various
      recovery stages after stroke are needed to further establish its utility in both
      clinical and research settings.

PMID- 16813475
TI  - Clinimetric properties of the performance-oriented mobility assessment.
AB  - BACKGROUND AND PURPOSE: The Performance-Oriented Mobility Assessment (POMA) is a
      widely used instrument that provides an evaluation of balance and gait. It is
      used clinically to determine the mobility status of older adults or to evaluate
      changes over time. To support the use of the POMA for these purposes, the
      clinimetric properties (in particular, responsiveness) were determined. SUBJECTS:
      Participants (78% female; mean age=84.9 years) were living in either self-care or
      nursing-care residences. Concurrent and discriminant validity were assessed with
      the total group (N=245), whereas reliability and responsiveness were determined
      with a subsample (n=30). Fall-related predictive validity was assessed with a
      subsample of 72 participants. METHODS: In addition to the POMA, several reference
      performance tests were administered. The POMA was assessed on 2 consecutive days
      by 2 raters (observers). The analyses included the calculation of Spearman rank
      correlation coefficients (R), limits of agreement (LOA) with Bland-Altman plots,
      minimal detectable changes at the 95% confidence level (MDC(95)), and sensitivity
      and specificity with regard to predicting falls. When possible, findings for the
      total scale (POMA-T) were complemented by findings for its balance subscale (POMA
      B) and its gait subscale (POMA-G). RESULTS: The interrater and test-retest
      reliability for the POMA-T and the POMA-B were good (R=.74-.93), whereas for the
      POMA-G, the reliability values, although high as well, were systematically
      slightly lower (R=.72-.89). The Spearman correlations with the reference
      performance tests (R=|.64|- |.68|) indicated satisfactory concurrent validity for
      the POMA-T and the POMA-B, but the corresponding findings for the POMA-G (R=|.52|
      |.56|) were less convincing. The discriminant validity values of the 3 scales
      were about the same. The LOA for the POMA-T were on the order of -4.0 to 4.0 for
      test-retest agreement and -3.0 to 3.0 for interrater agreement. On the basis of
      the MDC(95) values, it was concluded that changes in POMA-T scores at the
      individual level should be at least 5 points and that those at the group level
      (n=30) should be at least 0.8 point to be considered reliable. Even when optimal
      cutoff points were used, sensitivity and specificity values (varying between
      62.5% and 66.1%) for the POMA-T as well as for its 2 subscales indicated poor
      accuracy in predicting falls. DISCUSSION AND CONCLUSION: The POMA-T and its
      subscale POMA-B have adequate reliability and validity for assessing mobility in
      older adults. The POMA-T is useful for demonstrating intervention effects at the
      group level. Changes within subjects, however, should be at least 5 points before
      being interpreted as reliable changes. The accuracy of the POMA-T in predicting
      falls is poor.

PMID- 16813477
TI  - Effect of pelvic-floor muscle exercise position on continence and quality-of-life
      outcomes in women with stress urinary incontinence.
AB  - BACKGROUND AND PURPOSE: Pelvic-floor muscle (PFM) exercises are effective in
      reducing stress urinary incontinence (SUI), but few studies have investigated the
      effect of specific exercise variables on treatment outcomes. This study explored
      the effect of exercise position on treatment outcomes in women with SUI. SUBJECTS
      AND METHODS: Forty-four women were randomly assigned to exercise in the supine
      position only or in both supine and upright positions. Bladder diary, pad test,
      urodynamic test, quality-of-life (Incontinence Impact Questionnaire [IIQ]), and
      PFM strength outcomes were obtained at baseline and after treatment. RESULTS:
      Exercise position did not affect outcomes. After data from both groups were
      collapsed, statistically significant improvements with treatment were observed in
      bladder diary, IIQ, PFM strength, and urodynamic test results. DISCUSSION AND
      CONCLUSION: Exercise position did not differentially affect treatment outcomes.
      However, women in this study achieved a mean 67.9% reduction in the frequency of
      SUI episodes and improvements in other study outcomes.

PMID- 16813476
TI  - A systematic review of the effectiveness of exercise, manual therapy,
      electrotherapy, relaxation training, and biofeedback in the management of
      temporomandibular disorder.
AB  - BACKGROUND AND PURPOSE: This systematic review analyzed studies examining the
      effectiveness of various physical therapy interventions for temporomandibular
      disorder. METHODS: Studies met 4 criteria: (1) subjects were from 1 of 3 groups
      identified in the first axis of the Research Diagnostic Criteria for
      Temporomandibular Disorders, (2) the intervention was within the realm of
      physical therapist practice, (3) an experimental design was used, and (4) outcome
      measures assessed one or more primary presenting symptoms. Thirty studies were
      evaluated using Sackett's rules of evidence and 10 scientific rigor criteria.
      Four randomly selected articles were classified independently by 2 raters
      (interrater agreement of 100% for levels of evidence and 73.5% for methodological
      rigor). RESULTS: The following recommendations arose from the 30 studies: (1)
      active exercises and manual mobilizations may be effective; (2) postural training
      may be used in combination with other interventions, as independent effects of
      postural training are unknown; (3) mid-laser therapy may be more effective than
      other electrotherapy modalities; (4) programs involving relaxation techniques and
      biofeedback, electromyography training, and proprioceptive re-education may be
      more effective than placebo treatment or occlusal splints; and (5) combinations
      of active exercises, manual therapy, postural correction, and relaxation
      techniques may be effective. DISCUSSION AND CONCLUSION: These recommendations
      should be viewed cautiously. Consensus on defining temporomandibular joint
      disorder, inclusion and exclusion criteria, and use of reliable and valid outcome
      measures would yield more rigorous research.

PMID- 16813478
TI  - Functional electrical stimulation changes dynamic resources in children with
      spastic cerebral palsy.
AB  - BACKGROUND AND PURPOSE: Children with cerebral palsy (CP) often are faced with
      difficulty in walking. The purpose of this experiment was to determine the
      effects of functional electrical stimulation (FES) applied to the gastrocnemius
      soleus muscle complex on the ability to produce appropriately timed force and
      reduce stiffness (elastic property of the body) and on stride length and stride
      frequency during walking. SUBJECTS AND METHODS: Thirteen children with spastic CP
      (including 4 children who were dropped from the study due to their inability to
      cooperate) and 6 children who were developing typically participated in the
      study. A crossover study design was implemented. The children with spastic CP
      were randomly assigned to either a group that received FES for 15 trials followed
      by no FES for 15 trials or a group that received no FES for 15 trials followed by
      FES for 15 trials. The children who were having typical development walked
      without FES. Kinematic data were collected for the children with CP in each
      walking condition and for the children who were developing typically. Impulse
      (force-producing ability) and stiffness were estimated from an escapement-driven
      pendulum and spring system model of human walking. Stride length and stride
      frequency also were measured. To compare between walking conditions and between
      the children with CP and the children who were developing typically, dimensional
      analysis and speed normalization procedures were used. RESULTS: Nonparametric
      statistics showed that there was no significant difference between the children
      with CP in the no-FES condition and the children who were developing typically on
      speed-normalized dimensionless impulse. In contrast, the children with CP in the
      FES condition had a significantly higher median value than the children who were
      developing typically. The FES significantly increased speed-normalized
      dimensionless impulse from 10.02 to 16.32 when comparing walking conditions for
      the children with CP. No significant differences were found between walking
      conditions for stiffness, stride length, and stride frequency. DISCUSSION AND
      CONCLUSION: The results suggest that FES is effective in increasing impulse
      during walking but not in decreasing stiffness. The effect on increasing impulse
      does not result in more typical spatiotemporal gait parameters.

PMID- 16813479
TI  - Effects of two 4-week proprioceptive neuromuscular facilitation programs on
      muscle endurance, flexibility, and functional performance in women with chronic
      low back pain.
AB  - BACKGROUND AND PURPOSE: Improving functional performance in patients with chronic
      low back pain is of primary importance. The purpose of this study was to examine
      the effects of 2 proprioceptive neuromuscular facilitation (PNF) programs on
      trunk muscle endurance, flexibility, and functional performance in subjects with
      chronic low back pain (CLBP). SUBJECTS: Eighty-six women (40.2+/-11.9 [mean+/-SD]
      years of age) who had complaints of CLBP were randomly assigned to 3 groups:
      rhythmic stabilization training, combination of isotonic exercises, and control.
      METHODS: Subjects trained with each program for 4 weeks with the aim of improving
      trunk stability and strength. Static and dynamic trunk muscle endurance and
      lumbar mobility were measured before, at the end of, and 4 and 8 weeks after
      training. Disability and back pain intensity also were measured with the Oswestry
      Index. RESULTS: Multivariate analysis of variance indicated that both training
      groups demonstrated significant improvements in lumbar mobility (8.6%-24.1%),
      static and dynamic muscle endurance (23.6%-81%), and Oswestry Index (29.3%-31.8%)
      measurements. DISCUSSION AND CONCLUSION: Static and dynamic PNF programs may be
      appropriate for improving short-term trunk muscle endurance and trunk mobility in
      people with CLBP.

PMID- 16813480
TI  - Prognosis in soft tissue disorders of the shoulder: predicting both change in
      disability and level of disability after treatment.
AB  - BACKGROUND AND PURPOSE: Clinicians often are faced with questions about prognosis
      and outcome of shoulder disorders. The purpose of this study was to identify
      predictors of both change in disability and level of disability following
      physical therapy treatment. SUBJECTS: The subjects were consecutive patients
      (n=361) who were receiving physical therapy for soft tissue shoulder disorders.
      METHODS: Clinical response to physical therapy, which was measured using the
      Disabilities of the Arm, Shoulder, and Hand (DASH) measure, was assessed over 12
      weeks. The 28 independent baseline predictors included demographics, disorder
      related and disability measures, medication use, clinical findings, and
      expectations for recovery. Multiple linear regression techniques were used.
      RESULTS: Predictors of greater disability at discharge were: higher initial
      disability, therapist prediction of restricted activities at discharge, workers'
      compensation claim, older age, and being female. Predictors of greater
      improvement in disability were: shoulder surgery, higher pain intensity, shorter
      duration of symptoms, younger age, and poorer general physical health (measured
      using the 36-Item Short-Form Health Survey [SF-36]). DISCUSSION AND CONCLUSIONS:
      Prognostic factors differ depending on the format of the outcome. Only age was
      significant in both models.

PMID- 16813481
TI  - Awareness of risks of overweight among rural Australians.
AB  - INTRODUCTION: Overweight and obesity are highly prevalent in rural areas and pose
      significant risks to health. The aim of this study was to investigate whether the
      rural public in central Queensland are aware of the health risks of overweight
      and to determine whether their perceptions of weight status and methods used to
      assess weight status correspond with those of health professionals. METHODS:
      Adults were randomly selected from shoppers in shopping centres in Central
      Queensland, Australia, to self-complete a questionnaire that assessed
      participants' understanding of the health risks of overweight, perception of
      current weight, methods used to assess current weight and understanding of the
      concepts of body mass index (BMI) and waist-to-hip ratio (WHR). Participants were
      also asked to provide demographic details and self-report their height and
      weight. RESULTS: The majority of participants were appropriately aware that,
      regardless of their degree of physical activity, overweight is associated with
      increased risk of heart disease (92%), type 2 diabetes (83%) and stroke (83%). A
      large proportion were also aware of the association of overweight with sleep
      apnoea (69%), fertility problems (68%) and arthritis (57%) but few were aware of
      the link with asthma (35%) and various types of cancer (14-32%). Knowledge of the
      health risks of overweight did not differ greatly across the BMI spectrum, with
      similar beliefs expressed by those who were classified overweight or obese (based
      on self-reported data) and those who were not. Women were more aware of the
      health risks of overweight for type 2 diabetes and fertility problems, less
      likely to be overweight, and to more accurately perceive their weight status
      compared with men. The majority of participants used subjective measures to
      assess weight status and few used or understood BMI or WHR. CONCLUSIONS: Rural
      people in central Queensland appear to be well aware of the health risks of
      overweight but many are unable to identify overweight in themselves and few
      understand how to accurately gauge their weight status. This exploratory study
      highlights the need to educate people in these communities about accurate and
      objective measures to assess overweight and obesity. Further studies are needed
      to assess how common misperception of weight status is among rural populations in
      Australia and to determine whether this contributes to a higher prevalence of
      overweight and obesity in rural communities compared with urban areas.

PMID- 16813484
TI  - Are "drink responsibly" alcohol campaigns strategically ambiguous?
AB  - This article applies the concept of strategic ambiguity in examining viewer
      responses to brewer-sponsored "responsible drinking" television advertising
      campaigns. Strategically ambiguous messages are designed to engender diverse
      interpretations between varied audience segments, and these different selective
      perceptions should translate into relatively uniform positive corporate images.
      In this study, teenage and young adult respondents were shown a series of
      television spots from two leading alcohol companies. As predicted, there was a
      high degree of diversity in meanings of message content and campaign purpose
      derived by viewers, particularly among less sophisticated teenagers. Moreover,
      evaluative ratings of messages and sponsors were generally favorable and more
      uniform than interpretive responses. The research demonstrates how seemingly
      prohealth messages can serve to subtly advance both industry sales and public
      relations interests.

PMID- 16813485
TI  - Acceptance of Web-based personalized feedback: user ratings of an alcohol misuse
      prevention program targeting U.S. Marines.
AB  - The use of Web-based programs for a variety of health education, risk reduction,
      and health promotion purposes can be a valuable tool in the effort to improve the
      health of a population. Providing theory-based personalized feedback through such
      a method can be particularly useful in alcohol misuse prevention efforts. A brief
      alcohol use feedback program was developed for members of the U.S. Marine Corps,
      and user-satisfaction ratings were collected from 167 participants. Approximately
      44% of the sample found the program to be useful or very useful, and 46% of the
      sample reported that they were likely or very likely to recommend the Web site to
      others. The Web-based format with tailored responses was preferred by 85% of
      respondents over other more traditional methods of alcohol training, and 80% of
      participants felt that the feedback was appropriate for Marines in their
      community. Significantly higher usefulness, likelihood of recommending the
      program to others, and overall ratings of the program were reported among younger
      and nonheavy-drinking participants (p < .05). Results indicate that this
      computerized assessment and feedback program is a promising mechanism with which
      to provide personalized alcohol misuse prevention information.

PMID- 16813486
TI  - Evaluating the believability and effectiveness of the social norms message "most
      students drink 0 to 4 drinks when they party".
AB  - In an effort to reduce dangerous drinking levels among college students,
      university health educators have initiated social norms campaigns based on the
      rationale that students will be more likely to reduce their own drinking
      behaviors if they think that most students on campus are not heavy or binge
      drinkers. Within the framework of social comparisons theory, this study reports
      the findings of a survey of 277 college students and explores the correlates of
      accuracy and bias in students' estimates of whether or not most other students
      think that binge drinking on campus is a problem and whether or not most other
      students believe the campaign message. The overwhelming majority (72.6%) of
      students did not believe the norms message that most students on campus drink "0
      to 4" drinks when they party, and 52.7% reported drinking "5 or more" drinks in a
      sitting. The social norms campaign was effective in motivating 61% of the
      respondents to think about binge drinking as a problem. For the most part, group
      or social network norms were more influential on students' own drinking behavior
      than were their estimates of the campus drinking norm. The findings also clarify
      that accuracy in estimating the campus social norm in and of itself does not
      necessarily lead to an increase or reduction in alcohol consumption. The social
      comparisons approach underscores the complex and social nature of human
      interaction and reinforces the need for the development of multiple approaches to
      alcohol education with messages that are designed to target the specific needs of
      students based on their orientations toward alcohol consumption.

PMID- 16813487
TI  - Mexican American women in a rural area and barriers to their ability to enact
      protective behaviors against breast cancer.
AB  - Mexican American women in rural areas have less chance of surviving breast cancer
      than women in other ethnic populations (Boughton, 2000; Herman, 1996). This
      research sought to determine why such women do or do not enact behaviors to help
      them protect themselves from breast cancer. The extended parallel process model
      (Witte, 1994) provided a guiding theoretical basis for understanding perceptions,
      and 48 women, in discussion groups and surveys, were asked about self-exams,
      physician exams, and mammograms. Findings demonstrated that the women had high
      perceived self-efficacy and susceptibility regarding breast cancer but did not
      perceive it as severe (i.e., that it could cause death). These perceptions were
      positively and negatively related to behaviors that protect against breast
      cancer. Also, several barriers, such as lack of transportation, lack of access to
      health care, and lack of knowledge regarding breast self-exams, were found.

PMID- 16813488
TI  - The role of social support in the family and community integration of right
      hemisphere stroke survivors.
AB  - The goal of this project was to understand better the communicative processes by
      which social support can assist right-hemisphere stroke survivors in the process
      of community integration. Open-ended interviews were conducted with 12 right
      hemisphere stroke survivors and their family caregivers. The transcribed
      interviews revealed 7 challenges (physical, cognitive-perceptual, emotional,
      relationship, employment, financial, and challenges to activities of daily
      living) and three types of resources (formal external, informal external, and
      internal). Stroke survivors' internal resources were shown to be essential for
      facilitating community integration. Implications for researchers and health care
      providers are discussed within the framework of Hobfoll's (1988) conservation of
      resources theory.

PMID- 16813489
TI  - Using functional theory to promote HIV testing: the impact of value-expressive
      messages, uncertainty, and fear.
AB  - This study tests the utility of the functional theory of attitudes and arousal of
      fear in motivating college students to get tested for HIV. It is argued from the
      perspective of functional theory that value-expressive appeals to get tested for
      the purpose of taking care of one's own health could be effective if that goal is
      desired by message targets who are sexually active and unaware of their sexually
      transmitted disease status. As part of the process, the effectiveness of these
      appeals is increased by the arousal of uncertainty and fear. A model detailing
      the mediating processes is proposed and found to be consistent with the data.
      Overall, messages advocating testing for the self-interested reason of one's own
      health were more effective than messages advocating testing for the goal of
      protecting one's partners.

PMID- 16813490
TI  - Television illness depictions, identity, and social experience: responses to
      multiple sclerosis on The West Wing among people with MS.
AB  - This project contributes to our understanding of how audiences interpret
      televised depictions of illness by investigating responses to the depiction of
      multiple sclerosis (MS) on the television drama The West Wing from 1999 to 2002.
      The study employs qualitative methods, including a focus group, individual
      interviews, and the collection of electronic message board posts to investigate
      how people with MS interpret the dramatization of the illness. Findings are
      analyzed in terms of respondents' perceptions of (a) the portrayal of the
      physical disease, (b) the portrayal of the social dimensions of MS, and (c) the
      impact of this portrayal for themselves and others with the disease. The study
      found that participants engaged in self-comparisons with the depiction of MS
      within the program. These comparisons resulted in a range of reactions from
      individuals varying in relation with their multiple physical and social
      experiences with the illness. Thus, illness experience adds complexity to
      judgments about accuracy, meaning, and outcomes related to health depictions.
      Participants expressed a desire to see more symptoms depicted, and they noted
      concern about the identities communicated to the public about people with MS and
      its influence on their daily, lived experience.

PMID- 16813491
TI  - "It's not our ass": medical resident sense-making regarding lawsuits.
AB  - This study examined the accounts of 27 medical residents regarding how they make
      sense of their feelings about medical malpractice lawsuits and communication
      strategies to deal with mistakes. The study uncovered 4 distinct ways residents
      discursively constructed lawsuits--as inevitable, as recourse, as the result of
      unrealistic expectations, and as a gamble--and the implications of each
      construction. Further, the analysis suggests that it is essential to understand
      the role of the medical hierarchy and the resident-attending physician
      relationship to understand how residents make sense of their feelings toward
      lawsuits and strategies used to handle mistakes and the threat of lawsuits. The
      article concludes with implications for people supervising medical residents and
      for risk managers.

PMID- 16813492
TI  - Fear appeals for individuals in different stages of change: intended and
      unintended effects and implications on public health campaigns.
AB  - This study represents an initial attempt to examine the intended and unintended
      effects of fear appeals among individuals in different stages of change. Toward
      this end, a pilot study investigated the effects of fear appeals promoting skin
      cancer preventive behavior among college students. After being exposed to fear
      appeals, individuals who were in the precontemplation stage indicated a greater
      likelihood of thinking defensively and fatalistically regarding the facts on
      health risk than those who had intended to engage in or who had previously
      engaged in preventive behavior. Concurrently, after being exposed to fear
      appeals, those who were in the precontemplation stage reported less favorable
      attitudes toward message recommendations, weaker intentions to engage in
      recommended behavior, and less performance of preventive behavior than those who
      had contemplated or had previously engaged in preventive behavior. Implications
      of these results on future public health campaigns are discussed.

PMID- 16813493
TI  - Physicians' and patients' recognition of the level of the physician's explanation
      in medical encounters.
AB  - The association between patients' and physicians' evaluations of physicians'
      explanations of medical test results and diagnoses in actual practice was
      examined in this study. The participants were 630 physician-patient pairs in
      Japan. Loglinear models for matched-pairs data revealed the following: (a)
      Concerning the association between patients' and physicians' evaluations, the
      agreement plus uniform association model fit the data best, and (b) for the
      physicians' explanations, the physicians' and patients' judgment agreed on the
      explanation of the medical test results but not on the explanation of the
      diagnosis. In interacting with patients, physicians should bear in mind that
      their judgments do not always agree with those of patients with respect to the
      level of explanation necessary.

PMID- 16813495
TI  - Bibliography.

PMID- 16813503
TI  - No matter how well done, [corrected] HIV/AIDS CAM utilization papers in 2006 make
      us sad.

PMID- 16813504
TI  - Risking alternative and complementary medicine in the name of standardization.

PMID- 16813505
TI  - Effect of low doses and high homeopathic potencies in normal and cancerous human
      lymphocytes: an in vitro isopathic study.
AB  - OBJECTIVES: Biologic effects of high homeopathic potencies can be studied in cell
      cultures using cell lines or primary cells. We hypothesized that primary cells
      would be more apt to respond to high potencies than cell lines, especially cancer
      cell lines. We set out to investigate the effects of low doses and high
      homeopathic potencies of cadmium chloride, respectively, in an intoxication model
      with human primary lymphocytes compared to a human leukemia cell line (Jurkat).
      DESIGN: Cells were pretreated with either low concentrations (nM-microM) or high
      potencies (pool 15-20c) of cadmium for 120 hours, following which they were
      exposed to a toxic treatment with a range of cadmium concentrations (8-80 microM)
      during 24 hours. Cell viability was eventually assessed by use of the MTS/PES
      assay. Controls included a vehicle (NaCl 0.9%) for the low concentrations of
      cadmium or water 15-20c for cadmium 15-20c. A total of 34 experiments were
      conducted, 23 with low concentrations and 11 with high potencies of cadmium. Data
      were analyzed by analysis of variance. RESULTS: Pretreatment with low
      concentrations or high potencies of cadmium significantly increased cell
      viability in primary lymphocytes after toxic challenge, compared to control cells
      (mean effect +/- standard error = 19% +/- 0.9% for low concentrations
      respectively 8% +/- 0.6% for high potencies of cadmium; p < 0.001 in both cases).
      The pretreatment effect of low doses was significant also in cancerous
      lymphocytes (4% +/- 0.5%; p < 0.001), albeit weaker than in normal lymphocytes.
      However, high homeopathic potencies had no effect on cancerous lymphocytes (1% +/
      1.9%; p = 0.45). CONCLUSIONS: High homeopathic potencies exhibit a biologic
      effect on cell cultures of normal primary lymphocytes. Cancerous lymphocytes
      (Jurkat), having lost the ability to respond to regulatory signals, seem to be
      fairly unresponsive to high homeopathic potencies.

PMID- 16813506
TI  - Immolina, a high-molecular-weight polysaccharide fraction of Spirulina, enhances
      chemokine expression in human monocytic THP-1 cells.
AB  - INTRODUCTION: Spirulina (Spirulina platensis) is a dietary supplement valued for
      its immune-enhancing properties. We previously reported that the
      immunostimulatory effect of spirulina can be traced to a high-molecular- weight
      polysaccharide fraction. This fraction, labeled Immolina, activates nuclear
      factor kappa-B in human monocytic THP-1 cells and increases expression of
      proinflammatory cytokines. OBJECTIVE: To characterize further the
      immunostimulatory effects of Immolina on THP-1 cells, we evaluated its effect on
      genes encoding the chemokines interleukin (IL)-8, MCP-1, MIP-1alpha, MIP-1beta,
      IP-10, the cytokines tumor necrosis factor (TNF)-alpha, IL-1beta, and the enzyme
      cyclo-oxygenase-2 (COX-2). METHODS: THP-1 cells were exposed to concentrations of
      Immolina ranging from 1 ng/mL to 100 microg/mL and changes in gene expression
      were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). For
      comparison, THP-1 cells were activated with 1 ng/mL of TNF-alpha, 10 ng/mL of IL
      1beta, or 10 ng/mL of lipopolysaccharide using the same assay conditions. To
      assess the response of THP-1 cells to Immolina at the protein level, we probed
      culture supernatants using a cytokine array immunoblot assay. RESULTS: RT-PCR
      analysis revealed that Immolina dose-dependently increased the expression of all
      5 chemokines tested as well as the expression of TNF-alpha, IL-1beta, and COX-2.
      The cytokine array immunoblot assay revealed an increase in the chemokines IL-8
      and MIP-1beta. Thymidine uptake experiments verified that Immolina did not affect
      the viability and growth rate of THP-1 cells. CONCLUSIONS: The results of the
      experiments demonstrate that Immolina activates THP-1 cells in a manner that is
      consistent with the recruitment of diverse populations of leukocytes in response
      to inflammatory and infectious signals.

PMID- 16813507
TI  - Thermoluminescence in ultra-high dilution research.
AB  - OBJECTIVE: Thermoluminescence of homeopathically prepared ultra-high dilutions of
      lithium chloride in deuterium oxide (D2O) (10 (-30) g cm (-3); C15 LiCl in D2O)
      and similarly prepared D2O (C15 D2O) was compared in three experiments varying
      (1) time between preparation of substance and time of experimentation, and (2)
      time between irradiation and thermoluminescence recording. Data were also
      compared with a normal solution 0.1 M LiCl in D2O and with pure D2O. METHODS: To
      record thermoluminescence, the solutions were frozen in liquid nitrogen (77 K, 
      196 degrees C), irradiated with 1 kGy, and after a succession of definite storage
      periods, were progressively rewarmed to 238 K (-35 degrees C). RESULTS:
      Thermoluminescence patterns of C15 LiCl in D2O, C15 D2O, and D2O were similar.
      The average thermoluminescence intensity of C15 LiCl in D2O tended to be less
      than C15 D2O when tests were performed shortly after preparation of the
      substances and with short storage time between irradiation and recording of
      thermoluminescence. Thermoluminescence of D2O was significantly lower than from
      C15 D2O, particularly when the time between irradiation and recording was
      increased. CONCLUSION: The nature of the phenomena here described still remains
      unexplained. Nevertheless, data suggest that thermoluminescence might be
      developed into a promising tool to study homeopathically prepared ultra- high
      dilutions.

PMID- 16813508
TI  - The testing of classical pulse concepts in Chinese medicine: left- and right-hand
      pulse strength discrepancy between males and females and its clinical
      implications.
AB  - OBJECTIVES AND DESIGN: The use of the radial pulse as a diagnostic tool is an
      important part of the Chinese medicine (CM) clinical evaluation. This study
      reports the findings of an investigation into inter-arm pulse strength
      differences in subjects and the relationship to traditional pulse claims relating
      to gender. METHOD: Using a standardized pulse taking procedure and concrete
      operational definitions, two pulse assessors with a demonstrated high level of
      inter-rater agreement each assessed the overall left and right pulse strength and
      rated their findings on a standardized pulse form. RESULTS: The overall
      percentage of inter-rater agreement for manual assessment of dominant hand was
      86% (based on a cohort of 65 subjects). In relation to the three possible choices
      regarding dominant side (right, neither, left) the right-hand side was most
      commonly selected as relatively strongest of the two regardless of gender (60% of
      males and 71% of females). Analysis of the data using Chi-square (II) found the
      observed frequencies for an assessor's rating of dominant hand in males were
      significantly different to those expected according to CM theory. CONCLUSIONS:
      The CM assumption of gender-related pulse-strength differences in left and right
      hand pulses was not supported within this study.

PMID- 16813509
TI  - Complementary and alternative medicine therapies in acne, psoriasis, and atopic
      eczema: results of a qualitative study of patients' experiences and perceptions.
AB  - OBJECTIVES: The aim of this study was to explore the use of complementary and
      alternative medicine (CAM) therapies in patients with acne, psoriasis, or atopic
      eczema and the attitudes about CAM of these patients. DESIGN: This was a
      qualitative study, utilizing semistructured interviews and thematic analysis.
      SETTING: Patients were recruited from the practices of dermatologists and general
      practitioners in a noncapital Australian city. RESULTS: Twenty-six (26)
      interviews were conducted with patients with acne, 29 with psoriasis, and 7 with
      atopic eczema. Use of CAM therapies was common. Participants tended to value CAM
      over orthodox therapies because of their preference for natural approaches to
      their skin diseases and the perceived lesser potential for adverse effects of CAM
      therapies. Respondents with acne were more confident about the efficacy of CAM
      than were those with psoriasis or eczema. The resulting sense of control
      attenuated psychologic sequelae of acne. This was not apparent in psoriasis or
      eczema. CONCLUSIONS: Practitioners should be cognizant of the likely use of CAM
      and its implications (including the potential for attenuation of psychologic
      morbidity) in their patients who have skin diseases.

PMID- 16813510
TI  - Levels of commitment: exploring complementary therapy use by women with breast
      cancer.
AB  - OBJECTIVES: Previous research on complementary therapy use in populations of
      patients with breast cancer has failed to differentiate among the different types
      of therapies and utilization patterns, resulting in wide discrepancies in
      prevalence rates. The purpose of this study was to develop more refined and
      rigorous estimates of the prevalence of complementary therapy use in women with
      breast cancer and their level of commitment to complementary therapy. DESIGN AND
      SAMPLE/SETTING: Using a cross-sectional, retrospective survey design, a random
      sample of 334 women with breast cancer was drawn from a Canadian provincial
      cancer registry. Using an intensive therapy inventory, women were asked to
      indicate the therapies and practices they had used since cancer diagnosis,
      frequency of use, amount of effort associated with using each therapy, and
      financial cost of therapy use. RESULTS: A substantial proportion of women with
      breast cancer were found to be using complementary therapies, with between 19.5%
      (most conservative estimate) and 79.9% (liberal estimate) of the women reporting
      the use of at least one complementary therapy following diagnosis. While the
      majority of therapies were used on a daily basis, a minimal amount of effort and
      finances was expended on complementary therapy use. Using two-way cluster
      analysis, two homogenous groups of complementary therapy users were identified
      based on level of commitment to complementary therapy use. Women with a low
      commitment to complementary therapy use comprised 73.9% of the sample and were
      more likely to be older and report less education than women with a moderate-to
      high commitment to complementary therapy use. CONCLUSIONS: The use of
      complementary therapies by women with breast cancer warrants more precise
      measurement to accurately capture the types of complementary therapies used and
      the level of commitment to complementary therapy use. The findings of this study
      point to the value of the concept of commitment in identifying individuals
      willing to commit substantial time, energy and financial resources to
      complementary therapy use.

PMID- 16813511
TI  - Older adults' use of complementary and alternative medicine for mental health:
      findings from the 2002 National Health Interview Survey.
AB  - OBJECTIVES: To compare complementary and alternative medicine (CAM) use among
      adults 65 and older with and without self-reported anxiety or depression, and to
      investigate the prevalence and predictors of CAM use for treatment by persons
      with anxiety or depression. DESIGN: Cross-sectional survey. SETTINGS/LOCATION:
      Computer-assisted interviews conducted in participants' homes. SUBJECTS: Subjects
      included 5827 adults aged 65 and older who participated in the 2002 National
      Health Interview Survey including the Alternative Health Supplement.
      INTERVENTION: None. OUTCOME MEASURES: Overall use of CAM, use of four categories
      of CAM, and use of 20 CAM modalities. CAM use for treatment of any health
      condition, and CAM use to treat mental health. RESULTS: Eighty-one and seven
      tenths percent (81.7%) of older adults with self-reported anxiety or depression
      who used CAM in the past year, whereas 64.6% of older adults without these
      conditions used CAM. Differences in CAM use were driven by elevated use of
      spiritual practices, relaxation techniques, and use of nonvitamin, nonmineral
      natural products by patients with symptoms of mental conditions. Fewer than 20%
      of CAM users with self-reported anxiety or depression used CAM for their mental
      health. Few personal and health-related factors predicted CAM use for treatment
      among older adults with self-reported anxiety or depression. CONCLUSIONS: Older
      adults with self-reported anxiety or depression were more likely to use spiritual
      practices, relaxation techniques, and nonvitamin, nonmineral natural products
      than elders in good mental health. However, for the majority of older adults with
      self-reported anxiety or depression, CAM was used for purposes other than
      treating mental health.

PMID- 16813512
TI  - Prevalence of complementary and alternative medicine use among HIV patients for
      perceived lipodystrophy.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) use is common among some
      patients who test positive for human immunodeficiency virus (HIV). Changes in
      body-fat distribution can occur in some patients on prolonged highly active
      antiretroviral therapy. Currently, there are fewer effective treatments for the
      condition. Patients with lipodystrophy may be turning to CAM. OBJECTIVE: The
      objective was to investigate the prevalence and perceived benefit of CAM use for
      perceived body-shape changes among a cohort of HIV-positive patients.
      DESIGN/SETTING/SUBJECTS: We surveyed a cross-sectional convenience sample of 74
      patients from urban and suburban HIV outpatient clinics in Baltimore, MD, who
      indicated concerns about body-shape changes. The survey instrument was developed
      based on validated questionnaires previously used in clinical trials and
      published work. RESULTS: CAM use including both supplements and visits to CAM
      providers was 74% in our study population. In multivariate analysis, users of CAM
      were more likely to be men (p = 0.016) and to have noticed bodyshape changes
      after taking HIV medications (p = 0.012). However, very few subjects reported
      using CAM specifically for lipodystrophy changes. CAM use was more commonly
      reported for "general health." CAM was primarily more conventional, such as
      multivitamins or minerals, but several subjects reported using meditation and/or
      prayer (38%), ginseng (Panax spp.) (3%), St John's wort (Hypericum perforatum)
      (1%), and acupuncture (1%). More conventional CAM, such as exercise, diet, and
      vitamins as well as meditation/prayer were perceived to be effective for
      lipodystrophy as well as for improving the overall sense of well-being.
      CONCLUSIONS: The rate of CAM use among the HIV-positive population is high and is
      primarily used to improve general health.

PMID- 16813513
TI  - Policies for traditional medicine in peripheral China.
AB  - This paper examines the management and practice of traditional medicine in three
      autonomous regions of the People's Republic of China: Inner Mongolia; Tibet; and
      Xinjiang. On this basis, the paper considers how established medical traditions
      might best be integrated into modern health care systems. It holds that
      indigenous forms of medicine that have been practiced successfully across many
      generations should be treated as different but equal within wider health care
      systems. China has made important progress toward this ideal but, at the same
      time, has quite a long way to go. It is highly recommended that Chinese
      policymakers increase their efforts to give all established traditional medicines
      different but equal status within regional health care systems.

PMID- 16813514
TI  - Cochrane systematic reviews examine P6 acupuncture-point stimulation for nausea
      and vomiting.
AB  - BACKGROUND: In 1998, the National Institutes of Health Consensus Statement on
      Acupuncture concluded that promising results have emerged showing the efficacy of
      acupuncture in adult postoperative and chemotherapy induced nausea and vomiting.
      The acupuncture point, P6 had been the point used in most of the trials.
      OBJECTIVES: To summarize Cochrane systematic reviews assessing P6 stimulation for
      nausea and vomiting. RESULTS: Reviews were found on postoperative sickness,
      chemotherapy-induced nausea and vomiting, and pregnancy-related nausea and
      vomiting. Results for postoperative nausea and vomiting show the most consistent
      results with 26 trials and more than 3000 patients showing the superiority of
      real P6 stimulation over sham for both adults and children and for both nausea
      and vomiting. Pooled data of trials including different antiemetics showed that
      P6 stimulation seems to be superior to antiemetic medication for nausea and
      equivalent for vomiting. P6 stimulation was similarly effective across the
      different methods of stimulation, both invasive or noninvasive. Results for
      chemotherapy-induced nausea and vomiting showed 11 trials and over 1200 patients.
      Electroacupuncture, but not manual acupuncture, was beneficial for first-day
      vomiting. Acupressure was effective for first-day nausea but not vomiting.
      Wristwatch-like electrical devices were not effective for any outcome. Results
      for pregnancy-related nausea and vomiting comprised six trials and approximately
      1150 patients. Results were mixed with some trials showing positive and other
      trials equivocal results with no favor to a certain kind of method. CONCLUSIONS:
      P6 stimulation may be beneficial for various conditions involving nausea and
      vomiting. The added value to modern antiemetics remains unclear. In patients on
      chemotherapy, future research should focus on patients for whom the problems are
      refractory. The next steps in research should include investigating whether
      acupuncture points added to P6 or individualizing treatment based on a
      Traditional Chinese Medicine diagnosis increases treatment effectiveness. It
      would also be worthwhile to identify predictors of response across the different
      conditions so that the individual patients can optimize acupuncture point
      therapy.

PMID- 16813519
TI  - Expression of mouse osteoclast K-Cl Co-transporter-1 and its role during bone
      resorption.
AB  - To assess the role of Cl- transport during osteoclastic bone resorption, we
      studied the expression and function of K+/Cl- co-transporters (KCCs). KCC1 and
      chloride channel-7 were found to be expressed in mouse osteoclasts. The KCC
      inhibitor, R(+)-butylindazone (DIOA), KCC1 antisense oligo-nucleotides, and siRNA
      suppressed osteoclastic pit formation. DIOA also decreased Cl- extrusion and
      reduced H+ extrusion activity. These results show that KCC1 provides a Cl-
      extrusion mechanism accompanying the H+ extrusion during bone resorption.
      INTRODUCTION: Mice with deficient chloride (Cl-) channels, ClC7, show severe
      osteopetrosis, resulting from impairment of Cl- extrusion during osteoclastic
      bone resorption. However, the expression and functional role of Cl- transporters
      other than ClC7 in mammalian osteoclasts is unknown. The aim of this study was to
      determine expression of K+/Cl- co-transporters (KCCs) and their functional role
      for bone resorption in mouse osteoclasts. MATERIALS AND METHODS: Mouse
      osteoclasts were derived from cultured bone marrow cells with macrophage-colony
      stimulating factor (M-CSF) and RANKL or from co-culture of bone marrow cells and
      primary osteoblasts. We examined the expression of Cl- transporters using RT-PCR,
      immunochemical, and Western blot methods. The effects of Cl- transport inhibitors
      on H+ and Cl- extrusion were assessed by measuring intracellular H+ ([H+]i) and
      Cl- ([Cl-]i). The effects of inhibitors, antisense oligo-nucleotides, and siRNA
      for Cl- transporters on bone resorption activities were evaluated using a pit
      formation assay. RESULTS AND CONCLUSIONS: Mouse osteoclasts express not only ClC7
      but also K+/Cl- co-transporter mRNA. The existence of KCC1 in the cell membrane
      of mouse osteoclasts was confirmed by immunochemical staining and Western blot
      analysis. KCC inhibitors and Cl- channels blockers increased [Cl-]i and [H+]i in
      resorbing osteoclasts, suggesting that the suppression of Cl- extrusion through
      KCC and Cl- channels leads to reduced H+ extrusion activity. The combination of
      both inhibitors greatly suppressed these extrusion activities. KCC inhibitors and
      Cl- channel blockers also decreased osteoclastic bone resorption in our pit area
      essay. Furthermore, KCC1 antisense oligo-nucleotides and siRNA suppressed
      osteoclastic pit formation as well as treatment of ClC7 inhibitors. These results
      indicate that K+/Cl- co-transporter-1 expressed in mouse osteoclasts acts as a Cl
      extruder and plays an important role for H+ extrusion during bone resorption.

PMID- 16813520
TI  - Activation of Sirt1 decreases adipocyte formation during osteoblast
      differentiation of mesenchymal stem cells.
AB  - In vitro, mesenchymal stem cells differentiate to osteoblasts when exposed to
      bone-inducing medium. However, adipocytes are also formed. We showed that
      activation of the nuclear protein deacetylase Sirt1 reduces adipocyte formation
      and promotes osteoblast differentiation. INTRODUCTION: Mesenchymal stem cells
      (MSCs) can differentiate into osteoblasts, adipocytes, chondrocytes, and
      myoblasts. It has been suggested that a reciprocal relationship exists between
      the differentiation of MSCs into osteoblasts and adipocytes. Peroxisome
      proliferator-activated receptor gamma2 (PPARgamma2) is a key element for the
      differentiation into adipocytes. Activation of Sirt1 has recently been shown to
      decrease adipocyte development from preadipocytes through inhibition of
      PPARgamma2. MATERIALS AND METHODS: We used the mouse mesenchymal cell line
      C3H10T1/2 and primary rat bone marrow cells cultured in osteoblast
      differentiation medium with or without reagents affecting Sirt1 activity.
      Adipocyte levels were analyzed by light microscopy and flow cytometry (FACS)
      after staining with Oil red O and Nile red, respectively. Osteoblast and
      adipocyte markers were studied with quantitative real-time PCR. Mineralization in
      cultures of primary rat bone marrow stromal cells was studied by von Kossa and
      alizarin red staining. RESULTS: We found that Sirt1 is expressed in the
      mesenchymal cell line C3H10T1/2. Treatment with the plant polyphenol resveratrol
      as well as isonicotinamide, both of which activate Sirt1, blocked adipocyte
      development and increased the expression of osteoblast markers. Nicotinamide,
      which inhibits Sirt1, increased adipocyte number and increased expression of
      adipocyte markers. Furthermore, activation of Sirt1 prevented the increase in
      adipocytes caused by the PPARgamma-agonist troglitazone. Finally, activation of
      Sirt1 in rat primary bone marrow stromal cells increased expression of osteoblast
      markers and also mineralization. CONCLUSIONS: In this study, we targeted Sirt1 to
      control adipocyte development during differentiation of MSCs into osteoblasts.
      The finding that resveratrol and isonicotinamide markedly inhibited adipocyte and
      promoted osteoblast differentiation may be relevant in the search for new
      treatment regimens of osteoporosis but also important for the evolving field of
      cell-based tissue engineering.

PMID- 16813521
TI  - Homocysteine enhances bone resorption by stimulation of osteoclast formation and
      activity through increased intracellular ROS generation.
AB  - Hyperhomocystinemia is a modifiable risk factor for osteoporosis and fracture.
      Physiologic concentrations of Hcy directly activate osteoclast formation and
      activity through stimulation of p38 MAPK and integrin beta3. The effects of Hcy
      were mediated by generation of intracellular ROS. INTRODUCTION:
      Hyperhomocysteinemia is a modifiable risk factor for osteoporosis and its related
      bone fractures. It has been reported that bone resorption and turnover rate were
      increased in hyperhomocystinemia. Using mouse bone marrow cells, we examined the
      direct effects of homocysteine (Hcy) on osteoclast formation and activity.
      MATERIALS AND METHODS: Osteoclast formation was determined by TRACP staining and
      TRACP activity. Intracellular reactive oxygen species (ROS) generation was
      measured using a fluorescent probe, dichlorodihydrofluorescein diacetate.
      Intracellular signaling cascades of p38 mitogen-activated protein kinase (MAPK),
      extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and
      NF-kappaB were measured by Western blotting. Integrin beta3 mRNA levels were
      measured by RT-PCR. Actin ring formation and bone resorption assays were also
      performed. RESULTS: Physiologic concentrations of Hcy upregulated TRACP+
      multinucleated cells and TRACP activity, stimulated actin ring formation, and
      increased the number of nuclei per cell and the level of expression of integrin
      beta3 mRNA. In addition, Hcy increased bone resorption and stimulated p38 MAPK
      activity and intracellular reactive oxygen species (ROS) generation. All of these
      Hcy-induced changes were blocked by pretreatment with the antioxidant, N-acetyl
      cysteine. CONCLUSIONS: Hcy directly activates osteoclast formation and activity
      through increased generation of intracellular ROS. These findings suggest that,
      in individuals with mild to moderate hyperhomocystinemia, increased bone
      resorption by osteoclasts may contribute to osteoporosis and that an antioxidant
      may attenuate bone loss in these individuals.

PMID- 16813522
TI  - Fluid shear stress induces less calcium response in a single primary osteocyte
      than in a single osteoblast: implication of different focal adhesion formation.
AB  - The immediate calcium response to fluid shear stress was compared between
      osteocytes and osteoblasts on glass using real-time calcium imaging. The
      osteoblasts were responsive to fluid shear stress of up to 2.4 Pa, whereas the
      osteocytes were not. The difference in flow-induced calcium may be related to
      differences in focal adhesion formation. INTRODUCTION: To explore the immediate
      response to mechanical stress in a bone cell population, we examined flow-induced
      calcium transients. In addition, the involvement of focal adhesion-related
      calcium transients in response to fluid flow in the cells was studied. MATERIALS
      AND METHODS: Bone cells were isolated from 16-day-old embryonic chicken calvaria
      by serial treatment with EDTA and collagenase. Single cells on glass without
      intercellular connections were subjected to fluid flow, and intracellular calcium
      concentration was measured using imaging with fluo-3. The identification of cell
      populations in the same field was performed with a chick osteocyte-specific
      antibody, OB7.3, and an alkaline phosphatase substrate, ELF-97, for osteoblast
      identification afterward. Immunofluorescence staining of vinculin was performed
      to visualize focal adhesions. RESULTS: The percentage of cells responding to
      fluid shear stress at 1.2 Pa was 5.5% in osteocytes, 32.4% in osteoblasts, and
      45.6% in OB7.3/ELF-97-negative cells. Furthermore, osteoblasts and OB7.3/ELF-97
      negative cells were more responsive to 2.4 Pa than 1.2 Pa, whereas osteocytes
      were less responsive. The elevation of calcium transients over baseline did not
      show any significant differences in the populations. To elucidate the mechanism
      accounting for the fact that single osteocytes are less sensitive to fluid shear
      stress of up to 2.4 Pa than osteoblasts, we studied focal adhesion-related
      calcium transients. First, we compared focal adhesion formation between
      osteocytes and osteoblasts and found a larger number of focal adhesions in
      osteoblasts than in osteocytes. Next, when the cells were pretreated with GRGDS
      (0.5 mM) before flow treatment, a significant reduction of calcium transients in
      osteoblasts (18%) was observed, whereas calcium transients in osteocytes were not
      changed by GRGDS. Control peptide GRGES did not reduce the calcium transients in
      either cell type. Furthermore, we confirmed that osteoblasts in calvaria showed a
      marked formation of vinculin plaques in the periphery of the cells. However,
      osteocytes in calvaria showed faint vinculin plaques only at the base of the
      processes. CONCLUSIONS: On glass, single osteocytes are less sensitive to fluid
      shear stress up to 2.4 Pa than osteoblasts. The difference in calcium transients
      might be related to differences in focal adhesion formation. Shear stress of a
      higher magnitude or direct deformation may be responsible for the mechanical
      response of osteocytes in bone.

PMID- 16813523
TI  - Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during
      bone development.
AB  - In this study, overexpression of noggin, a BMP antagonist, in developing bone
      caused significantly decreased osteoclast number as well as bone formation rate,
      resulting in increased bone mass with immature bone quality. BMP signaling plays
      important roles in normal bone development and regulation of bone resorption.
      INTRODUCTION: Bone morphogenetic proteins (BMPs) act on various types of cells.
      Although involvement of BMP signals in osteoblast differentiation has been
      studied extensively, the effects of BMPs on osteoclasts have not been widely
      researched. Consequently, the net effects of BMPs on bone remain unclear. The
      purpose of this study was to delineate more fully the role of BMPs in skeletal
      biology. MATERIALS AND METHODS: We generated transgenic mice that express BMP4 or
      noggin in bone under the control of the 2.3-kb alpha1(I) collagen chain gene
      (Col1a1) promoter, and analyzed their bone phenotype. We also analyzed bone of
      transgenic mice expressing BMP4 specifically in cartilage. RESULTS: Mice
      overexpressing BMP4 in bone developed severe osteopenia with increased osteoclast
      number. Mice overexpressing noggin, a BMP antagonist, in bone showed increased
      bone volume associated with decreased bone formation rate and decreased
      osteoclast number. The noggin-transgenic tibias exhibited reduced periosteal bone
      formation and reduced resorption of immature bone in marrow spaces, associated
      with frequent fractures at the diaphysis. Co-culture of primary osteoblasts
      prepared from noggin-transgenic calvariae and wildtype spleen cells resulted in
      poor osteoclast formation, which was rescued by addition of recombinant BMP2,
      suggesting that noggin inhibits osteoclast formation by attenuating BMP
      activities in noggin-transgenic mice. The expression levels of Rankl were not
      decreased in primary osteoblasts from noggin transgenic mice. Immunoblot analysis
      showed increased phosphorylation of Smad1/5/8 in osteoclast precursor cells after
      20-minute treatment with BMPs, suggesting that these cells are stimulated by
      BMPs. Mice overexpressing BMP4 in cartilage had enlarged bones containing thick
      trabeculae, possibly because of expansion of cartilage anlagen. CONCLUSIONS:
      Overexpression of noggin in bone revealed that BMP signals regulate bone
      development through stimulation of osteoblasts and osteoclasts.

PMID- 16813524
TI  - Different roles of Runx2 during early neural crest-derived bone and tooth
      development.
AB  - We compared gene expression profiles between Runx2 null mutant mice and their
      wildtype littermates. Most Runx2-dependent genes in bones were different from
      those in teeth, implying that the target genes of Runx2 are tissue-dependent. In
      vitro experiments determined that Runx2 is a part of the FGF and BMP signaling
      pathways in tooth and bone development, respectively. INTRODUCTION: Runx2 (Cbfa1)
      is expressed in the neural crest-derived mesenchyme of developing bone and tooth.
      Runx2 homozygous null mice lack bone through a failure in osteoblast
      differentiation and have arrested tooth development at the late bud stage. The
      aim of this study was to discover and compare the identities and the roles of
      Runx2 target genes in bone and tooth development. MATERIALS AND METHODS: Wildtype
      and Runx2-/- tissue was collected from mouse embryos, and gene expression was
      compared by Affymetrix microarray analysis and radioactive in situ hybridization
      of embryonic tissue sections (E12-E14). Induction of target genes by growth
      factors in bone and tooth tissue was studied using in vitro experiments,
      including a novel method involving hanging-drop cultures and RT-PCR. RESULTS:
      Thirteen bone and four tooth genes were identified that are Runx2-dependent. The
      identities of these genes do not significantly overlap between bone and tooth,
      indicating tissue specificity of several genes regulated by Runx2. Genes
      downregulated in bone development in Runx2 null mutants were Bambi, Bmp4, Bono1,
      Dkk1, Fgf receptor1, Gli1, Lef1, Patched, Prostaglandin F receptor1, Tcf1,
      Tgfbeta1, Wnt10a, and Wnt10b. Several of these genes were induced by BMPs in bone
      tissue in a Runx2-independent manner. Genes downregulated in tooth development
      were Dkk1, Dusp6, Enpp1, and Igfbp3. These genes were all induced by fibroblast
      growth factors (FGFs) in dental tissue. FGF-induction of Dkk1 was completely
      dependent on Runx2 function. CONCLUSIONS: The contrasting identities and
      distinctive mechanisms that stimulate the expression of Runx2-dependent genes in
      bone and tooth development imply that the developmental roles of Runx2 in these
      separate tissues are different. In tooth development, Dkk1 may be a direct
      transcriptional target of Runx2. Bone genes were stimulated by BMP4 before the
      formation of the ossification center, suggesting that BMPs may mediate the early
      epithelial-mesenchymal interactions involved in bone formation.

PMID- 16813525
TI  - Pathogenic role of connective tissue growth factor (CTGF/CCN2) in osteolytic
      metastasis of breast cancer.
AB  - The role of CTGF/CCN2 in osteolytic metastasis by breast cancer cells and its
      mechanism of action were studied. Osteolytic metastasis accompanied by CCN2 and
      PTHrP overproduction was efficiently inhibited by an anti-CCN2 antibody.
      Furthermore, we found that CCN2 was induced by PTHrP through PKA-, PKC-, and ERK
      mediated pathways therein. INTRODUCTION: Connective tissue growth factor
      (CTGF/CCN2) is a mediator of local angiogenesis induced by breast cancer, but its
      role in osteolytic metastasis has not been evaluated. PTH-related peptide (PTHrP)
      is another critical factor in the development of the osteolytic metastasis. Using
      both in vivo and in vitro approaches, we studied whether/how neutralization of
      CCN2 prevented bone metastasis and how PTHrP signaling is related. MATERIALS AND
      METHODS: A mouse model of bone metastasis by human breast cancer cell line MDA231
      was treated with a CCN2-neutralizing antibody, and osteolytic bone metastases
      were assessed on radiographs and immunohistochemistry. Ccn2 gene expression and
      transcription were examined by Northern blot and luciferase analysis. Immunoblot
      analysis and kinase inhibitors were used to identify the signaling pathways
      implicated. Anti-angiogenic/osteoclastogenic effects of ccn2 downregulation were
      also evaluated. RESULTS: Treatment of mice with a CCN2-neutralizing antibody
      greatly decreased osteolytic bone metastasis, microvasculature, and osteoclasts
      involved. The antibody also suppressed the growth of subcutaneous tumor in vivo
      and proliferation and migration of human umbilical vein endothelial cells
      (HUVECs) in vitro. Downregulation of ccn2 also repressed osteoclastogenesis. CCN2
      expression was specifically observed in cancer cells producing PTHrP and type I
      PTH/PTHrP receptor (PTH1R) invaded the bone marrow, and PTHrP strongly
      upregulated ccn2 in MDA231 cells in vitro. Activation of protein kinase C (PKC)
      and protein kinase A (PKA) was necessary and sufficient for the stimulation of
      ccn2 by PTHrP. Indeed, inhibition of the extracellular signal-regulated kinase
      (ERK1/2), PKC, or PKA by specific inhibitors counteracted the stimulation of ccn2
      expression. Incubation of MDA231 cells with PTHrP induced the activation of
      ERK1/2. Consistent with these findings, inhibition of PKC prevented PTHrP-induced
      ERK1/2 activation, whereas 12-O-tetradecanoylphorbol13-acetate (TPA), a
      stimulator of PKC, upregulated it. CONCLUSIONS: CCN2 was critically involved in
      osteolytic metastasis and was induced by PKA- and PKC-dependent activation of
      ERK1/2 signaling by PTHrP. Thus, CCN2 may be a new molecular target for anti
      osteolytic therapy to shut off the PTHrP-CCN2 signaling pathway.

PMID- 16813526
TI  - Periosteal remodeling at the femoral neck in nonhuman primates.
AB  - Periosteal bone turnover is poorly understood. We documented intramembranous
      periosteal bone turnover in the femoral neck in intact nonhuman primates and an
      increase in osteoclast numbers at the periosteal surface in sex steroid-deficient
      animals. Our studies are the first to systematically document periosteal turnover
      at the femoral neck. INTRODUCTION: Bone size is an important determinant of bone
      strength, and cellular events at the periosteal surface could alter bone
      dimensions. We characterized periosteal cellular activity with dynamic
      histomorphometric studies of nonhuman primate femoral neck and shaft. MATERIALS
      AND METHODS: Femur specimens from 16 intact adult male and female nonhuman
      primates (Rhesus [Macaca mulatta, n = 9] and Japanese Macaque [Macaca fuscata, n
      = 7]) were analyzed. Animals were double-labeled with tetracycline, and necropsy
      was performed 2-7 days after the last dose. We characterized periosteal
      resorptive activity in an additional group of five intact and four castrate
      female animals. Multiple group comparisons in intact animals were performed by
      one-way ANOVA followed by a Fisher PLSD posthoc test. In gonadectomized animals,
      Fisher's exact test was used for dichotomous and Mann-Whitney U-test for
      continuous variables. RESULTS: Bone turnover in the periosteum of the femoral
      neck in intact animals was more rapid than at the femoral shaft but slower than
      in femoral neck cancellous bone. Similarly, in these intact animals, the eroded
      surface of cortical bone at the femoral neck periosteal surface was significantly
      greater than in the cancellous bone compartment (p < 0.0001) or on the femoral
      shaft (p < 0.0001). Gonadectomized female animals showed an increase in
      osteoclast number on the periosteal surface compared with intact controls (p <
      0.01). CONCLUSIONS: We documented intramembranous periosteal bone turnover in the
      femoral neck by histomorphometric analyses. The tissue level bone formation rate
      was sufficient to add substantively to femoral neck size over time. Periosteal
      osteoclastic activity was not the result of the emergence of intracortical
      tunneling at the bone surface. Sex steroid deficiency produced an increase in
      osteoclast numbers at the periosteal surface. This is the first systematic
      documentation of periosteal turnover at the femoral neck.

PMID- 16813527
TI  - Strain-dependent variations in the response of cancellous bone to ovariectomy in
      mice.
AB  - The goal of this study was to characterize the skeletal response to ovariectomy
      in mice (129P3, C57BL/6, and B6129PF2) commonly used in gene manipulation studies
      to evaluate their potential as preclinical models of postmenopausal osteoporosis.
      The magnitude of cancellous bone loss and cellular indices of increased bone
      turnover in response to ovariectomy varied with mouse type and skeletal site, but
      in general, were less pronounced and less consistent than in Sprague-Dawley rats,
      the established preclinical model for postmenopausal bone loss. INTRODUCTION: The
      ovariectomized (OVX) rat is the most widely used preclinical rodent model for
      postmenopausal osteoporosis. However, the underlying mechanisms of bone
      disorders, including osteoporosis, have been explored predominantly in the mouse.
      The purpose of this study was to evaluate mice (129P3 and C57BL/6 inbred strains
      and their F2 hybrid offspring, B6129PF2), commonly used for gene knockout and
      overexpression studies, for their potential as preclinical models of
      postmenopausal bone loss. MATERIALS AND METHODS: The mice were OVX or sham
      operated at 4 months of age and killed at 1 or 3 months after surgery. Lumbar
      vertebrae and distal femora were subjected to histomorphometric assessment.
      RESULTS: Mice in the two strains and the F2 hybrids (will be referred to as
      strain for the remainder of the abstract) lost vertebral cancellous bone after
      OVX; bone volume (BV/TV) was 20% and 27% lower at 1 and 3 months after surgery,
      respectively. The decreased cancellous BV/TV was associated with an increase in
      osteoclast surface at 1 month after OVX in the 129P3 strain only. Osteoblast
      surface was increased by 20% with OVX at both 1 and 3 months after surgery,
      irrespective of mouse strain. However, bone formation rate was not altered by OVX
      in any of the mouse strains. In contrast to the lumbar vertebrae, cancellous bone
      loss in response to OVX differed in the distal femur among the three mouse
      strains. OVX had no significant effect on distal femur BV/TV in the B6129PF2
      mouse strain. In the C57BL/6 strain, cancellous BV/TV was reduced by OVX at 1
      month after surgery but not at 3 months after surgery, whereas distal femur BV/TV
      in 129P3 mice was reduced at 3 months after surgery. Osteoclast surface was not
      affected by OVX at either time-point in the C57BL/6 strain, but was increased by
      116% at 1 month after surgery in the 129P3 strain. Osteoblast surface was
      increased with OVX at 1 month after surgery, irrespective of strain, whereas bone
      formation rate was not altered by OVX at either time-point in any of the strains.
      CONCLUSIONS: The magnitude of cancellous bone loss and cellular indices of
      increased bone turnover in response to OVX varied with mouse strain and skeletal
      site, but in general, were less pronounced and less consistent than in the
      Sprague-Dawley rat. Although mouse models will continue to provide insights into
      genetic influences on bone mass and turnover, caution should be exercised when
      using 129P3 and C57BL/6 mice, and their F2 hybrids, as models for postmenopausal
      bone loss and preclinical testing of potential therapies for osteoporosis.

PMID- 16813528
TI  - TNF-alpha mediates p38 MAP kinase activation and negatively regulates bone
      formation at the injured growth plate in rats.
AB  - TNF-alpha is known to inhibit osteoblast differentiation in vitro and yet it is
      essential for bone fracture repair. Roles of TNF-alpha in the bony repair of
      injured growth plate were examined in young rats treated with a TNF-alpha
      antagonist. The results show that TNF-alpha mediates p38 activation, which
      influences the recruitment, proliferation, and osteoblast differentiation of
      mesenchymal cells and negatively regulates bone formation at the injured growth
      plate. INTRODUCTION: TNF-alpha inhibits expression of osteoblast differentiation
      factor cbfa1 and osteoblast differentiation in vitro and yet TNF-alpha signaling
      is essential for bone fracture healing. Roles of TNF-alpha in the bony repair of
      injured growth plate cartilage are unknown. MATERIALS AND METHODS: Roles of TNF
      alpha in the activation of p38 mitogen activated protein (MAP) kinase and the
      subsequent bony repair of the injured growth plate were examined in young rats
      receiving the TNF-alpha inhibitor ENBREL or saline control. Activation of p38 was
      determined by Western blot analysis and immunohistochemistry. Inflammatory cell
      counts on day 1, measurements of repair tissue proportions, and counting of
      proliferative mesenchymal cells on day 8 at growth plate injury site were carried
      out (n = 6). Expression of inflammatory cytokines TNF-alpha and IL-1beta,
      fibrogenic growth factor (FGF)-2, cbfa1, and bone protein osteocalcin at the
      injured growth plate was assessed by quantitative RT-PCR. Effects of TNF-alpha
      signaling on proliferation, migration, and apoptosis of rat bone marrow
      mesenchymal cells (rBMMCs) and the regulatory roles of p38 in these processes
      were examined using recombinant rat TNF-alpha, ENBREL, and the p38 inhibitor
      SB239063 in cultured primary rBMMCs. RESULTS: p38 activation was induced in the
      injured growth plate during the initial inflammatory response, and activated p38
      was immunolocalized in inflammatory cells at the injury site and in the adjacent
      growth plate. In addition, activation of p38 was blocked in rats treated with TNF
      alpha antagonist, suggesting a role of TNF-alpha in p38 activation. Whereas TNF
      alpha inhibition did not alter inflammatory infiltrate and expression of TNF
      alpha and IL-1beta at the injured growth plate on day 1, it reduced mesenchymal
      infiltrate and cell proliferation and FGF-2 expression on day 8. Consistently,
      TNF-alpha increased proliferation and migration of rBMMCs in vitro, whereas p38
      inhibition reduced rBMMC proliferation and migration. At the injured growth plate
      on day 8, TNF-alpha inhibition increased expression of cbfa1 and osteocalcin and
      increased trabecular bone formation at the injury site. There was a significant
      inverse correlation between TNF-alpha and cbfa1 expression levels, suggesting a
      negative relationship between TNF-alpha and cbfa1 in this in vivo model.
      CONCLUSIONS: These observations suggest that TNF-alpha activates p38 MAP kinase
      during the inflammatory response at the injured growth plate, and TNF-alpha-p38
      signaling seems to be required for marrow mesenchymal cell proliferation and
      migration at the growth plate injury site and in cell culture. Furthermore, TNF
      signaling has an inhibitory effect on bone formation at the injured growth plate
      by suppressing bone cell differentiation and bone matrix synthesis at the injury
      site.

PMID- 16813529
TI  - Disease status in autosomal dominant osteopetrosis type 2 is determined by
      osteoclastic properties.
AB  - Asymptomatic gene carriers and clinically affected ADO2 subjects have the same
      ClCN7 mutation. We examined osteoclastic bone resorption in vitro as well as
      osteoclast formation, several markers, acid secretion, and cytoskeletal
      structure. We found that ADO2 expression results from osteoclast specific
      properties. INTRODUCTION: Autosomal dominant osteopetrosis type II (ADO2) is a
      heritable osteosclerotic disorder that results from heterozygous mutations in the
      ClCN7 gene. However, of those individuals with a ClCN7 mutation, one third are
      asymptomatic gene carriers who have no clinical, biochemical, or radiological
      manifestations. Disease severity in the remaining two thirds is highly variable.
      MATERIALS AND METHODS: Human peripheral blood mononuclear cells were isolated and
      differentiated into osteoclasts by stimulation with hRANKL and human macrophage
      colony stimulating factor (hM-CSF). Study subjects were clinically affected
      subjects, unaffected gene carriers, and normal controls (n = 6 in each group).
      Pit formation, TRACP staining, RANKL dose response, osteoclast markers, acid
      secretion, F-actin ring, and integrin alpha(v)beta3 expression and co
      localization were studied. RESULTS: Osteoclasts from clinically affected subjects
      had severely attenuated bone resorption compared with those from normal controls.
      However, osteoclasts from unaffected gene carriers displayed similar bone
      resorption to those from normal controls. In addition, the resorption lacunae
      from both unaffected gene carriers and normal controls appeared much earlier and
      spread much more rapidly than those from clinically affected subjects. As time
      progressed, the distinction between clinically affected subjects and the other
      two groups increased. No significant difference was found in acidic secretion or
      osteoclast formation between the three groups. Osteoclast cytoskeletal
      organization showed no difference between the three groups but there was low
      cellular motility in clinically affected subjects. CONCLUSIONS: Osteoclasts from
      the unaffected gene carriers, in contrast to those from the clinically affected
      subjects, functioned normally in cell culture. This finding supports the
      hypothesis that intrinsic osteoclast factors determine disease expression in
      ADO2. Further understanding of this mechanism is likely to lead to the
      development of new approaches to the treatment of clinically affected patients.

PMID- 16813530
TI  - Mutations in OSTM1 (grey lethal) define a particularly severe form of autosomal
      recessive osteopetrosis with neural involvement.
AB  - We report three novel osteopetrosis patients with OSTM1 mutations and review two
      that have been previously described. Our analysis suggests that OSTM1 defines a
      new subset of patients with severe central nervous system involvement. This
      defect is also present in the gl mouse, which could represent a good model to
      study the role of the gene in the pathogenesis of this disease. INTRODUCTION:
      Autosomal recessive osteopetrosis (ARO) is a severe hereditary bone disease whose
      cellular basis is in the osteoclast, but with heterogeneous molecular defects. In
      addition to the TCIRG1 and the ClCN7 genes, whose mutations account for
      approximately 55% and 10% of cases, respectively, the OSTM1 gene has been
      described thus far in only two ARO patients. materials and methods: We report
      here three novel ARO patients presenting with severe primary central nervous
      system involvement in addition to the classical stigmata of severe bone
      sclerosis, growth failure, anemia, thrombocytopenia, and visual impairment with
      optic atrophy. In addition we analyzed the brain morphology and histology of the
      grey lethal mutant mouse. RESULTS: The analysis of the OSTM1 gene in two
      patients, both from Kuwait, showed homozygous two nucleotide deletion in exon 2,
      leading to a frameshift and premature termination. The third (Lebanese) patient
      showed a single point mutation in exon 1, leading to a nonsense mutation. The
      clinical neurological evaluation of the two Kuwaiti patients by CT and MRI scans
      showed a defect in the white matter, with a specific diagnosis of severe cerebral
      atrophy. The gl brain showed a diffuse translucent appearance with loss of the
      normal demarcation between the white and the grey matter, features consistent
      with myelin loss or hypomyelination. Histological and myelin staining analysis
      evidenced an atrophy of the corpus callosum with loss of myelin fibers, and in
      cortical areas, loss of the normal lamination consistent with multiple foci of
      cortical dysplasia. CONCLUSIONS: These findings suggest that OSTM1-dependent ARO
      defines a new subset of patients with severe central nervous system involvement
      leading to a very poor prognosis. The fact that central nervous system
      involvement is also present in the gl mouse mutant suggests that this mouse is a
      good model to test possible therapies.

PMID- 16813531
TI  - Effects of 3- and 5-year treatment with risedronate on bone mineralization
      density distribution in triple biopsies of the iliac crest in postmenopausal
      women.
AB  - Long-term effects of risedronate on bone mineralization density distribution in
      triple transiliac crest biopsies of osteoporotic women were evaluated. In this
      double-blinded study, 3- and 5-year treatment with risedronate increased the
      degree and homogeneity of mineralization without producing hypermineralization.
      These changes at the material level of bone could contribute to risedronate's
      antifracture efficacy. INTRODUCTION: Risedronate, a nitrogen-containing
      bisphosphonate, is widely used in the treatment of osteoporosis. It reduces bone
      turnover, increases BMD, and decreases fracture risk. To date, there are no data
      available on the long-term effects of risedronate on bone mineralization density
      distribution (BMDD) in humans. MATERIALS AND METHODS: Osteoporotic women enrolled
      in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo
      for up to 5 years. All subjects received calcium and vitamin D supplementation if
      deficient at baseline. Triple iliac crest biopsies were collected from a subset
      of these subjects at baseline and 3 and 5 years. BMDD was measured in these
      biopsies using quantitative backscattered electron imaging, and the data were
      also compared with a normal reference group. RESULTS: At baseline, both
      risedronate and placebo groups had a lower degree and a greater heterogeneity of
      mineralization as well as an increase in low mineralized bone compared with the
      normal reference group. The degree of mineralization increased significantly in
      the risedronate as well as in the placebo group after 3- and 5-year treatment
      compared with baseline. However, the degree of mineralization did not exceed that
      of normal. Three-year treatment with risedronate significantly increased the
      homogeneity of mineralization and slightly decreased low mineralized bone
      compared with placebo. Surprisingly with 5-year risedronate treatment,
      heterogeneity of mineralization increased compared with 3-year treatment, which
      might indicate an increase in newly formed bone. CONCLUSIONS: Long-term treatment
      with risedronate affects the homogeneity and degree of mineralization without
      inducing hypermineralization of the bone matrix. These changes at the material
      level of the bone matrix may contribute to risedronate's antifracture efficacy in
      osteoporotic patients.

PMID- 16813532
TI  - Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in
      women eighty years of age and older.
AB  - Strontium ranelate produces an early and sustained reduction of both vertebral
      and nonvertebral fractures in patients > or = 80 years of age. INTRODUCTION:
      About 25-30% of the population burden of all fragility fractures in the community
      arise from women > or = 80 years of age, because this population is at high risk
      for all types of fracture, particularly nonvertebral fractures. Despite this,
      evidence that therapies reduce the risk of both vertebral and nonvertebral
      fractures in this group is lacking. The aim of this study was to determine
      whether strontium ranelate, an agent that reduces the risk of vertebral and
      nonvertebral fractures in postmenopausal women >50 years of age, also reduces
      fractures in the elderly. MATERIALS AND METHODS: An analysis based on preplanned
      pooling of data from two international, phase III, randomized, placebo
      controlled, double-blind studies (the Spinal Osteoporosis Therapeutic
      Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]) included
      1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X
      rays were performed in 895 patients. Only radiographically confirmed nonvertebral
      fractures were included. RESULTS: Baseline characteristics did not differ in
      placebo and treatment arms. In the intent-to-treat analysis, the risk of
      vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral)
      fractures was reduced within 1 year by 59% (p = 0.002), 41% (p = 0.027), and 37%
      (p = 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and
      clinical fracture risks were reduced by 32% (p = 0.013), 31% (p = 0.011), and 22%
      (p = 0.040), respectively. The medication was well tolerated, and the safety
      profile was similar to that in younger patients. CONCLUSIONS: Treatment with
      strontium ranelate safely reduces the risk of vertebral and nonvertebral
      fractures in women with osteoporosis > or = 80 years of age. Even in the oldest
      old, it is not too late to reduce fracture risk.

PMID- 16813533
TI  - Heritability of changes in bone size and bone mass with age in premenopausal
      white sisters.
AB  - Femoral neck area expands and BMD decreases in premenopausal women. We used
      longitudinal DXA measurements on 388 premenopausal white sisters to show
      significant heritability of the rates of change in femoral neck area, BMC, and
      BMD. INTRODUCTION: Bone mass and structure are highly heritable. However, genetic
      effects on age-related changes in bone mass and structure in adults have been
      much less studied. MATERIALS AND METHODS: DXA measurements were made on 388
      healthy white premenopausal sisters from 178 families. Rates of change in femoral
      neck area, BMC, and BMD, as well as body weight, were calculated from two
      measurements made an average of 5.7 years apart. Mixed models were used to test
      whether bone changes were related to age or weight change. Variance components
      models were used to estimate the heritability of the rates of change. A method
      was proposed to correct for the underestimation of heritabilities caused by
      measurement errors of the rates of change. RESULTS: Femoral neck area increased
      with age, whereas BMD decreased. All of the rates of change at the femoral neck
      were positively correlated with weight change, but the rates of femoral neck
      changes did not vary with age. Adjusted for weight change, change in femoral neck
      BMC became negative. Significant heritabilities (0.29-0.36) were detected for
      changes in femoral neck BMC, BMD, and area adjusted for weight changes.
      Correction for DXA measurement error in the rate estimates increased the
      heritability estimates (from 0.29-0.36 range to 0.37-0.64 range). CONCLUSIONS:
      Rates of change are heritable for femoral neck area, BMC, and BMD in
      premenopausal white women.

PMID- 16813534
TI  - Relationship between bone quantitative ultrasound and fractures: a meta-analysis.
AB  - The relationship between bone QUS and fracture risk was estimated in a systematic
      review of data from 14 prospective studies of 47,300 individuals and 2350
      incident fractures. In older women, low QUS values were associated with overall
      fracture risk, low-trauma fractures, and with hip, forearm, and humerus fractures
      separately. INTRODUCTION: Bone quantitative ultrasound (QUS) has emerged as a
      promising technique to evaluate bone status. The aim of this study was to
      determine the association between measurements of QUS with the risk of fracture.
      MATERIALS AND METHODS: A meta-analysis of prospective cohort studies published
      between 1985 and June 2005 with a baseline measurement of QUS and subsequent
      follow-up for fractures was carried out. Fourteen separate study populations,
      consisting of about 47,300 individuals (85.4% women), with about 124,000 person
      years of observation and over 2350 fractures, including 653 hip, 529 forearm, and
      386 humeral fractures, were analyzed. The main outcome measure was the estimated
      relative risk of fracture for a decrease in bone QUS parameters of 1 SD below sex
      and age-adjusted mean in women. RESULTS: Eleven studies evaluated QUS at the
      heel, with patella and phalanx (two studies each) and distal radius (one study)
      being scarcely used. There was not significant heterogeneity among the studies
      included in the review. Relative risk estimates (95% CI) for overall fractures
      were 1.55 (1.35-1.78) for each SD decrease in broadband ultrasound attenuation
      (BUA), 1.63 (1.37-1.93) for speed of sound (SOS), and 1.74 (1.39-2.17) for QUS
      index/stiffness index (QUI/SI). Risk estimates were similar or slightly higher
      for hip fractures and low-energy trauma fractures. Humeral and forearm/wrist
      fractures were also related with lower QUS values. CONCLUSIONS: Measurements of
      bone QUS are significantly associated with nonspinal fracture risk in older women
      in a similar degree to DXA. QUS may be a valid alternative to evaluate fracture
      risk in situations where DXA is not accessible.

PMID- 16813535
TI  - A novel mutation (K378X) in the sequestosome 1 gene associated with increased NF
      kappaB signaling and Paget's disease of bone with a severe phenotype.
AB  - Sequestosome 1/p62 (p62) mutations are associated with PDB; however, there are
      limited data regarding functional consequences. We report a novel mutation in
      exon 7 (K378X) in a patient with polyostotic Paget's disease of bone. p62 mutants
      increased NF-kappaB activation and significantly potentiated osteoclast formation
      and bone resorption in human primary cell cultures. INTRODUCTION: Sequestosome
      1/p62 (p62) mutations are associated with Paget's disease of bone (PDB); however,
      there are limited data regarding functional consequences. One report has linked
      the common P392L mutation in the p62 ubiquitin binding associated (UBA) domain
      with increases in NF-kappaB activity, a transcription factor essential for
      osteoclastogenesis. To further clarify the functional impact of p62 mutations
      associated with PDB, we assessed the effect of p62 mutation (a novel mutation:
      K378X, and previously reported mutations: P392L and E396X) on RANK-induced NF
      kappaB activation and compared this with the effect of wildtype p62. In addition,
      we studied the effect of p62 mutation on osteoclast formation and bone
      resorption. MATERIALS AND METHODS: We performed co-transfection experiments with
      expression plasmids for p62 (wildtype or mutated) and RANK and an NF-kappaB
      luciferase reporter gene. Luciferase activities were recorded after addition of
      luciferin to cellular lysates. RAW(264.7) cells stably expressing enhanced green
      fluorescent protein (EGFP)-tagged p62 (wildtype, K378X, or P392L) or EGFP alone
      were assessed for changes in cell proliferation. Additionally, these cells were
      stimulated with RANKL to produce osteoclast-like cells (OLCs). Primary human
      monocytes collected from the K378X-affected patient and a control subject were
      stimulated to form OLCs and bone resorption data were obtained. RESULTS: The
      novel mutation introduces a premature stop codon in place of Lys-378 and thereby
      eliminates the entire p62 UBA domain; this and two additional natural mutations
      (P392L, E396X) increased NF-kappaB activation compared with wildtype p62.
      Wildtype p62 consistently inhibited NF-kappaB activation compared with empty
      vector. UBA mutations (K378X and P392L) significantly increased the number of
      OLCs formed in response to RANKL and also the number of nuclei of the OLCs. K378X
      affected human monocytes formed more OLCs with more nuclei and increased bone
      resorption compared with control monocytes. CONCLUSIONS: Our data show that
      mutation of the p62 UBA domain results in increased activation of NF-kappaB and
      osteoclast formation and function compared with wildtype p62. These results may
      partially explain the mechanism by which p62 mutation contributes to the
      pathogenesis of PDB.

PMID- 16813536
TI  - Quality among a diversity of health care providers. .
AB  - Thirty years' experience in the US with non-physician clinicians shows they can
      deliver quality care.

PMID- 16813537
TI  - Physician assistants and nurse practitioners: the United States experience.
AB  - Physician assistants (PAs) and nurse practitioners (NPs) were introduced in the
      United States in 1967. As of 2006, there are 110 000 clinically active PAs and
      NPs (comprising approximately one sixth of the US medical workforce).
      Approximately 11 200 new PAs and NPs graduate each year. PAs and NPs are well
      distributed throughout primary care and specialty care and are more likely than
      physicians to practise in rural areas and where vulnerable populations exist. The
      productivity of NPs and PAs, based on traditional doctor services, is comparable,
      and the range of services approaches 90% of what primary care physicians provide.
      The education time is approximately half that of a medical doctor and entry into
      the workforce is less restrictive. The interprofessional skill mix provided by
      PAs and NPs may enhance medical care in comparison with that provided by a doctor
      alone.

PMID- 16813538
TI  - Workforce substitution and primary care.
AB  - We must preserve the elements of our health care system that work well.

PMID- 16813539
TI  - Advanced nurse roles in UK primary care.
AB  - Nurses increasingly work as substitutes for, or to complement, general
      practitioners in the care of minor illness and the management of chronic
      diseases. Available research suggests that nurses can provide as high quality
      care as GPs in the provision of first contact and ongoing care for unselected
      patients. Reductions in cost are context dependent and rarely achieved. This is
      because savings on nurses' salaries are often offset by their lower productivity
      (due to longer consultations, higher patient recall rates, and increased use of
      tests and investigations). Gains in efficiency are not achieved when GPs continue
      to provide the services that have been delegated to nurses, instead of focusing
      on the services that only doctors can provide. Unintended consequences of
      extending nursing roles include loss of personal continuity of care for patients
      and increased difficulties with coordination of care as the multidisciplinary
      team size increases. Rapid access to care is, however, improved. There is a high
      capital cost involved in moving to multidisciplinary teams because of the need to
      train staff in new ways of working; revise legislation governing scope of
      practice; address concerns about legal liability; and manage professional
      resistance to change. Despite the unintended consequences and the high costs,
      extending nursing roles in primary care is a plausible strategy for improving
      service capacity without compromising quality of care or health outcomes for
      patients.

PMID- 16813540
TI  - The medical care practitioner: developing a physician assistant equivalent for
      the United Kingdom.
AB  - A range of demographic, social and other factors are creating a crisis in the
      provision of clinical care in the United Kingdom for which the physician
      assistant (PA) model developed in the United States appears to offer a partial
      solution. Local and national moves are underway to develop a similar cadre of
      registered health care professionals in England, with the current title of
      medical care practitioners (MCPs). A competence and curriculum framework document
      produced by a national steering group has formed the basis for a recent
      consultation process. A limited evaluation of US-trained PAs working in the West
      Midlands region of England in both primary care and acute secondary care suggests
      that PA activity is similar to that of doctors working in primary care and to
      primary care doctors working in the accident and emergency setting. The planned
      introduction of MCPs in England appears to offer, first, an effective strategy
      for increasing medical capacity, without jeopardising quality in frontline
      clinical services; and, second, the prospect of increased flexibility and
      stability in the medical workforce. The deployment of MCPs may offer advantages
      over increasing the number of doctors or taking nurses out of nursing roles. The
      introduction of MCPs may also enhance service effectiveness and efficiency.

PMID- 16813541
TI  - Task substitution: where to from here?
AB  - Meeting future health workforce needs is a challenge for all health
      professionals.

PMID- 16813542
TI  - Principles for supporting task substitution in Australian general practice.
AB  - The workforce crisis in Australian general practice provides an impetus to
      consider new roles for other health professionals. Any innovations need to be
      appraised in advance for their potential risks and benefits. We propose six
      principles for this appraisal. These are the need for the new roles to: support
      the relationship between patients and their general practitioners; be clearly
      defined, aligned with competency and with relevant professional registration; be
      supported by practice systems providing safeguards against medical error; be
      underpinned by a system ensuring informed patient consent to activities being
      undertaken by members of the general practice team; be supported by effective
      medical indemnity insurance and be supported with appropriate financing.

PMID- 16813543
TI  - Task transfer: the view of the Royal Australasian College of Physicians.
AB  - Health service imperatives such as workforce shortages of doctors and nurses and
      changing models of care are driving task transfer in Australia. The Royal
      Australasian College of Physicians (RACP) supports task transfer both across its
      specialty groups and to other health professionals as appropriate. The RACP's new
      education standards, with explicit curricula and competency-based assessments,
      underpin its capacity for task transfer. Task transfer must be evidence-based,
      safe, cost-efficient and facilitate best patient care.

PMID- 16813544
TI  - Task transfer: the view of the Royal Australasian College of Surgeons.
AB  - The Royal Australasian College of Surgeons (RACS) supports the evolution of
      appropriate task transfer in a team environment led by the most experienced
      clinician - in our case, the surgeon. A clear requirement needs to be identified
      for task transfer; it should not be used to avoid redressing the current
      inefficient use of existing surgeons resulting from ongoing underfunding.
      Maintenance of standards, defined curricula, professional titles and monitored
      outcomes are essential.

PMID- 16813545
TI  - Task substitution: the view of the Australian Medical Association.
AB  - Technology, community expectations and an ageing population are driving the need
      for an expanded health care workforce. Doctors embrace task substitution wherever
      it can be done safely and effectively. Task substitution should occur in the
      context of: team care that synergises the different skills of doctors, nurses and
      other health professionals doctors retaining their central role increases in the
      capacity to extend medical services with efficiency gains no loss of patient
      safety no fragmentation of care The growth of task substitution could lead to
      workforce shortages in other health care areas. Public policy on task
      substitution must take full account of patient preferences and expectations.

PMID- 16813546
TI  - Task transfer: another pressure for evolution of the medical profession.
AB  - Since the 1960s, Australian society and the medical profession have undergone
      enormous change. Our society has moved from a relatively homogeneous and
      conservative community, supported by limited government services, to one that is
      multicultural, focused on the individual and consumerism, and supported by
      extensive government programs, with health care a top public and political
      priority. A defining feature of contemporary society is its mistrust of
      institutions, professionals, public servants and politicians. The medical
      profession has changed from a cohesive entity, valuing generalism and with
      limited specialisation, to one splintered by ultra-specialisation and competing
      professional agendas. The medical workforce shortage and efforts to maintain the
      safety and quality of health services are putting acute pressure on the
      profession. Task transfer or role substitution of medical services is mooted as a
      potential solution to this pressure. This has the potential to drastically
      transform the profession. How task transfer will evolve and change medicine
      depends on the vision and leadership of the profession and a flexible pragmatism
      that safeguards quality and safety and places patient priorities above those of
      the profession.

PMID- 16813547
TI  - A radical new treatment for the sick health workforce.
AB  - The health workforce crisis needs radical treatment; simply educating more health
      workers will be insufficient, and role substitution among existing health workers
      is untenable. We propose a new class of health worker who would take on single
      disease or single procedure responsibilities, working mostly to protocols; and be
      embedded within current structures. We also propose modular health education
      which has fewer entry points into the health system, allows transfer between
      different disciplines, and is based on modules that can be accumulated to allow
      progress through the system to gain more clinical responsibility.

PMID- 16813548
TI  - Re-inventing medical work and training: a view from generation X.
AB  - Medical career preferences are changing, with doctors working fewer hours and
      seeking "work-life balance". There is an urgent need for creative workplace
      redesign if Australia is to have a sustainable health care system. Postgraduate
      medical education must adapt to changing medical roles. Curricula should be
      outcomes-based, should allow flexible delivery, and should consider future
      workforce needs.

PMID- 16813549
TI  - When the tide goes out: health workforce in rural, remote and Indigenous
      communities.
AB  - There is compelling evidence for the success of the "rural pipeline" (rural
      student recruitment and rurally based education and professional training) in
      increasing the rural workforce. The nexus between clinical education and
      training, sustaining the health care workforce, clinical research, and quality
      and safety needs greater emphasis in regional areas. A "teaching health system"
      for non-metropolitan Australia requires greater commitment to teaching as core
      business, as well as provision of infrastructure, including accommodation, and
      access to the private sector. Workforce flexibility is mostly well accepted in
      rural and remote areas. There is room for expanding the scope of clinical
      practice by non-medical clinicians in both an independent codified manner (eg,
      nurse practitioners) and through flexible local medical delegation (eg, practice
      nurses, Aboriginal health workers, and therapists). The imbalance between
      subspecialist and generalist medical training needs to be addressed. Improved
      training and recognition of Aboriginal health workers, as well as continued
      investment in Indigenous entry to other health professional programs, remain
      policy priorities.

PMID- 16813550
TI  - Aboriginal health workers and diabetes care in remote community health centres: a
      mixed method analysis.
AB  - OBJECTIVE: To assess the effect of employing Aboriginal health workers (AHWs) on
      delivery of diabetes care in remote community health centres, and to identify
      barriers related to AHWs' involvement in diabetes and other chronic illness care.
      DESIGN, SETTING AND PARTICIPANTS: Three-year follow-up study of 137 Aboriginal
      people with type 2 diabetes in seven remote community health centres in the
      Northern Territory. MAIN OUTCOME MEASURES: Delivery of guideline-scheduled
      diabetes services; intermediate outcomes (glycated haemoglobin [HbA(1c)] and
      blood pressure levels); number and sex of AHWs at health centres over time;
      barriers to AHWs' involvement in chronic illness care. RESULTS: There was a
      positive relationship between the number of AHWs per 1000 residents and delivery
      of guideline-scheduled diabetes services (but not intermediate health outcomes).
      Presence of male AHWs was associated with higher adherence to the guidelines.
      Barriers to AHWs' involvement in chronic illness care included inadequate
      training, lack of clear role divisions, lack of stable relationships with non
      Aboriginal staff, and high demands for acute care. CONCLUSIONS: Employing AHWs is
      independently associated with improved diabetes care in remote communities. AHWs
      have potentially important roles to play in chronic illness care, and service
      managers need to clearly define and support these roles.

PMID- 16813551
TI  - The efficacy of a nurse-led preoperative cataract assessment and postoperative
      care clinic.

PMID- 16813552
TI  - Return to workforce-based training.

PMID- 16813553
TI  - How not to effect change in curricula.

PMID- 16813554
TI  - Altruism can no longer support community-based training.

PMID- 16813555
TI  - Medical student access to patients.

PMID- 16813556
TI  - National exit exam needed to test core knowledge.

PMID- 16813557
TI  - Rural internship for final-year medical students.

PMID- 16813558
TI  - Registrars cannot provide full teaching for juniors.

PMID- 16813559
TI  - Medical student input to workforce planning.

PMID- 16813560
TI  - Lessons to be learnt from general practice training.

PMID- 16813561
TI  - Identification of a novel NADH-specific aldo-keto reductase using sequence and
      structural homologies.
AB  - The AKRs (aldo-keto reductases) are a superfamily of enzymes which mainly rely on
      NADPH to reversibly reduce various carbonyl-containing compounds to the
      corresponding alcohols. A small number have been found with dual NADPH/NADH
      specificity, usually preferring NADPH, but none are exclusive for NADH. Crystal
      structures of the dual-specificity enzyme xylose reductase (AKR2B5) indicate that
      NAD+ is bound via a key interaction with a glutamate that is able to change
      conformations to accommodate the 2'-phosphate of NADP+. Sequence comparisons
      suggest that analogous glutamate or aspartate residues may function in other AKRs
      to allow NADH utilization. Based on this, nine putative enzymes with potential
      NADH specificity were identified and seven genes were successfully expressed and
      purified from Drosophila melanogaster, Escherichia coli, Schizosaccharomyces
      pombe, Sulfolobus solfataricus, Sinorhizobium meliloti and Thermotoga maritima.
      Each was assayed for co-substrate dependence with conventional AKR substrates.
      Three were exclusive for NADPH (AKR2E3, AKR3F2 and AKR3F3), two were dual
      specific (AKR3C2 and AKR3F1) and one was specific for NADH (AKR11B2), the first
      such activity in an AKR. Fluorescence measurements of the seventh protein
      indicated that it bound both NADPH and NADH but had no activity. Mutation of the
      aspartate into an alanine residue or a more mobile glutamate in the NADH-specific
      E. coli protein converted it into an enzyme with dual specificity. These results
      show that the presence of this carboxylate is an indication of NADH dependence.
      This should allow improved prediction of co-substrate specificity and provide a
      basis for engineering enzymes with altered co-substrate utilization for this
      class of enzymes.

PMID- 16813562
TI  - Protein phosphatase 1 regulates the stability of the circadian protein PER2.
AB  - The circadian clock is regulated by a transcription/translation negative feedback
      loop. A key negative regulator of circadian rhythm in mammals is the PER2
      (mammalian PERIOD 2) protein. Its daily degradation at the end of the night
      accompanies de-repression of transcription. CKI (casein kinase I ) has been
      identified as the kinase that phosphorylates PER2, targeting it for ubiquitin
      mediated proteasomal degradation. We now report that PER2 degradation is also
      negatively regulated by PP1 (protein phosphatase 1)-mediated dephosphorylation.
      In Xenopus egg extract, PP1 inhibition by Inhibitor-2 accelerated mPER2
      degradation. Co-immunoprecipitation experiments showed that PER2 bound to PP1c in
      transfected HEK-293 cells. PP1 immunoprecipitated from HEK-293 cells, mouse liver
      and mouse brain, dephosphorylated CKI-phosphorylated PER2, showing that PER2 is a
      substrate for mammalian endogenous PP1. Moreover, over-expression of the dominant
      negative form of PP1c, the D95N mutant, accelerated ubiquitin and proteasome
      mediated degradation of PER2, and shortened the PER2 half-life in HEK-293 cells.
      Over-expression of the PP1 inhibitors, protein phosphatase 1 holoenzyme inhibitor
      1 and Inhibitor-2, confirmed these results. Thus PP1 regulates PER2 stability and
      is therefore a candidate to regulate mammalian circadian rhythms.

PMID- 16813563
TI  - Transmembrane segment 7 of human P-glycoprotein forms part of the drug-binding
      pocket.
AB  - P-gp (P-glycoprotein; ABCB1) protects us by transporting a broad range of
      structurally unrelated compounds out of the cell. Identifying the regions of P-gp
      that make up the drug-binding pocket is important for understanding the mechanism
      of transport. The common drug-binding pocket is at the interface between the
      transmembrane domains of the two homologous halves of P-gp. It has been shown in
      a previous study [Loo, Bartlett and Clarke (2006) Biochem. J. 396, 537-545] that
      the first transmembrane segment (TM1) contributed to the drug-binding pocket. In
      the present study, we used cysteine-scanning mutagenesis, reaction with an MTS
      (methanethiosulfonate) thiol-reactive analogue of verapamil (termed MTS
      verapamil) and cross-linking analysis to test whether the equivalent
      transmembrane segment (TM7) in the C-terminal-half of P-gp also contributed to
      drug binding. Mutation of Phe728 to cysteine caused a 4-fold decrease in apparent
      affinity for the drug substrate verapamil. Mutant F728C also showed elevated
      ATPase activity (11.5-fold higher than untreated controls) after covalent
      modification with MTS-verapamil. The activity returned to basal levels after
      treatment with dithiothreitol. The substrates, verapamil and cyclosporin A,
      protected the mutant from labelling with MTS-verapamil. Mutant F728C could be
      cross-linked with a homobifunctional thiol-reactive cross-linker to cysteines
      I306C(TM5) and F343C(TM6) that are predicted to line the drug-binding pocket.
      Disulfide cross-linking was inhibited by some drug substrates such as Rhodamine
      B, calcein acetoxymethyl ester, cyclosporin, verapamil and vinblastine or by
      vanadate trapping of nucleotides. These results indicate that TM7 forms part of
      the drug-binding pocket of P-gp.

PMID- 16813564
TI  - Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin
      (MP4): dissociation between in vitro and in vivo oxidation rates.
AB  - Haemoglobin-based oxygen carriers can undergo oxidation of ferrous haemoglobin
      into a non-functional ferric form with enhanced rates of haem loss. A recently
      developed human haemoglobin conjugated to maleimide-activated poly(ethylene
      glycol), termed MP4, has unique physicochemical properties (increased molecular
      radius, high oxygen affinity and low cooperativity) and lacks the typical
      hypertensive response observed with most cell-free haemoglobin solutions. The
      rate of in vitro MP4 autoxidation is higher compared with the rate for unmodified
      SFHb (stroma-free haemoglobin), both at room temperature (20-22 degrees C) and at
      37 degrees C (P<0.001). This appears to be attributable to residual catalase
      activity in SFHb but not MP4. In contrast, MP4 and SFHb showed the same
      susceptibility to oxidation by reactive oxygen species generated by a xanthine
      xanthine oxidase system. Once fully oxidized to methaemoglobin, the rate of in
      vitro haem loss was five times higher in MP4 compared with SFHb in the fast
      phase, which we assign to the beta subunits, whereas the slow phase (i.e. haem
      loss from alpha chains) showed similar rates for the two haemoglobins. Formation
      of MP4 methaemoglobin in vivo following transfusion in rats and humans was slower
      than predicted by its first-order in vitro autoxidation rate, and there was no
      appreciable accumulation of MP4 methaemoglobin in plasma before disappearing from
      the circulation. These results show that MP4 oxidation and haem loss
      characteristics observed in vitro provide information regarding the effect of
      poly(ethylene glycol) conjugation on the stability of the haemoglobin molecule,
      but do not correspond to the oxidation behaviour of MP4 in vivo.

PMID- 16813565
TI  - Dimerization of ubiquilin is dependent upon the central region of the protein:
      evidence that the monomer, but not the dimer, is involved in binding presenilins.
AB  - Ubiquilin proteins have been shown to interact with a wide variety of other
      cellular proteins, often regulating the stability and degradation of the
      interacting protein. Ubiquilin contains a UBL (ubiquitin-like) domain at the N
      terminus and a UBA (ubiquitin-associated) domain at the C-terminus, separated by
      a central region containing Sti1-like repeats. Little is known about regulation
      of the interaction of ubiquilin with other proteins. In the present study, we
      show that ubiquilin is capable of forming dimers, and that dimerization requires
      the central region of ubiquilin, but not its UBL or the UBA domains. Furthermore,
      we provide evidence suggesting that monomeric ubiquilin is likely to be the
      active form that is involved in binding presenilin proteins. Our results provide
      new insight into the regulatory mechanism underlying the interaction of ubiquilin
      with presenilins.

PMID- 16813566
TI  - Inhibition of plasminogen activator inhibitor-1 binding to endocytosis receptors
      of the low-density-lipoprotein receptor family by a peptide isolated from a phage
      display library.
AB  - The functions of the serpin PAI-1 (plasminogen activator inhibitor-1) are based
      on molecular interactions with its target proteases uPA and tPA (urokinase-type
      and tissue-type plasminogen activator respectively), with vitronectin and with
      endocytosis receptors of the low-density-lipoprotein family. Understanding the
      significance of these interactions would be facilitated by the ability to block
      them individually. Using phage display, we have identified the disulfide
      constrained peptide motif CFGWC with affinity for natural human PAI-1. The three
      dimensional structure of a peptide containing this motif (DVPCFGWCQDA) was
      determined by liquid-state NMR spectroscopy. A binding site in the so-called
      flexible joint region of PAI-1 was suggested by molecular modelling and validated
      through binding studies with various competitors and site-directed mutagenesis of
      PAI-1. The peptide with an N-terminal biotin inhibited the binding of the uPA-PAI
      1 complex to the endocytosis receptors low-density-lipoprotein-receptor-related
      protein 1A (LRP-1A) and very-low-density-lipoprotein receptor (VLDLR) in vitro
      and inhibited endocytosis of the uPA-PAI-1 complex in U937 cells. We conclude
      that the isolated peptide represents a novel approach to pharmacological
      interference with the functions of PAI-1 based on inhibition of one specific
      molecular interaction.

PMID- 16813567
TI  - Isolation and characterization of recombinant Drosophila Copia aspartic
      proteinase.
AB  - The wild type Copia Gag precursor protein of Drosophila melanogaster expressed in
      Escherichia coli was shown to be processed autocatalytically to generate two
      daughter proteins with molecular masses of 33 and 23 kDa on SDS/PAGE. The active
      site motif of aspartic proteinases, Asp-Ser-Gly, was present in the 23 kDa
      protein corresponding to the C-terminal half of the precursor protein. The coding
      region of this daughter protein (152 residues) in the copia gag gene was
      expressed in E. coli to produce the recombinant enzyme protein as inclusion
      bodies, which was then purified and refolded to create the active enzyme. Using
      the peptide substrate His-Gly-Ile-Ala-Phe-Met-Val-Lys-Glu-Val-Asn (cleavage site:
      Phe-Met) designed on the basis of the sequence of the cleavage-site region of the
      precursor protein, the enzymatic properties of the proteinase were investigated.
      The optimum pH and temperature of the proteinase toward the synthetic peptide
      were 4.0 and 70 degrees C respectively. The proteolytic activity was increased
      with increasing NaCl concentration in the reaction mixture, the optimum
      concentration being 2 M. Pepstatin A strongly inhibited the enzyme, with a Ki
      value of 15 nM at pH 4.0. On the other hand, the active-site residue mutant, in
      which the putative catalytic aspartic acid residue was mutated to an alanine
      residue, had no activity. These results show that the Copia proteinase belongs to
      the family of aspartic proteinases including HIV proteinase. The B-chain of
      oxidized bovine insulin was hydrolysed at the Leu15-Tyr16 bond fairly
      selectively. Thus the recombinant Copia proteinase partially resembles HIV
      proteinase, but is significantly different from it in certain aspects.

PMID- 16813568
TI  - Selective purification of supercoiled plasmid DNA from clarified cell lysates
      with a single histidine-agarose chromatography step.
AB  - The ability to isolate sc (supercoiled) pDNA (plasmid DNA) isoform should be one
      of the features of a pDNA purification process, eliminating sample contaminants
      such as RNA, gDNA (genomic DNA), proteins and endotoxins. A process is described
      that uses a single histidine-agarose chromatography step to purify sc pDNA from
      other isoforms and Escherichia coli impurities present in a clarified lysate. The
      histidine-agarose support combines the mild hydrophobic characteristics of an
      epoxy spacer arm with a pseudo-affinity histidine ligand. The 6 kb DNA vaccine
      backbone pVAX1-LacZ was used as a model target. Following loading at high salt
      [2.3 M (NH4)2SO4], the different species were eluted by a series of reverse salt
      step gradients (2.0, 1.5 and 0 M (NH4)2SO4). Open circular pDNA and gDNA was
      eluted at 2.3 M, sc pDNA was isolated as a single peak at 2.0 M and RNA was
      eluted at 1.5 M (NH4)2SO4 and lower. The underlying mechanism is thought to
      involve not only hydrophobic interactions between the support and pDNA molecules,
      but also non-specific biorecognition of nucleic acid bases by the histidine
      ligand. Control analysis showed that the isolated sc pDNA conforms to
      specifications in terms of gDNA (3.4 ng/microg of pDNA), endotoxins (0.02
      endotoxin unit/microg of pDNA), RNA and proteins (undetectable) and pDNA
      homogeneity (approximately 100% sc). Furthermore, the transfection efficiency of
      Chinese-hamster ovary cells (50%) was significantly higher when compared with the
      efficiency (25%) of a pDNA control. The present study confirms the possibility of
      using a single histidine-agarose chromatography step to purify sc pDNA from other
      isoforms and host contaminants present in a clarified E. coli lysate.

PMID- 16813569
TI  - Cell cycle-dependent expression of cIAP2 at G2/M phase contributes to survival
      during mitotic cell cycle arrest.
AB  - cIAP2 (cellular inhibitor of apoptosis protein 2) is induced by NF-kappaB
      (nuclear factor kappaB) when cells need to respond quickly to different apoptotic
      stimuli. A recent study using cDNA microarray technology has suggested that cIAP2
      transcription is regulated in a cell cycle-dependent manner, although the
      mechanism for such regulation is unknown. In this study, we confirmed the cell
      cycle-dependent regulation of cIAP2 expression at both the mRNA and protein
      levels. Additionally, we found that a bipartite CDE (cell cycle-dependent
      element)/CHR (cell cycle gene homology region) element in the cIAP2 promoter
      mediates cIAP2 gene activation in G2/M phase. Cell cycle-dependent G2/M-phase
      specific cIAP2 expression is enhanced by NF-kappaB activation, and selective down
      regulation of cIAP2 causes cells blocked in mitosis with nocodazole to become
      susceptible to apoptosis, indicating that the G2/M-phase-specific expression of
      cIAP2 contributes to the survival of mitotically arrested cells. Our studies
      describing the NF-kappaB-independent G2/M-phase-specific expression of cIAP2 will
      help in further understanding the molecular basis of cIAP2 over-expression in a
      variety of human cancers.

PMID- 16813570
TI  - Syphilis: no longer a historical disease.

PMID- 16813571
TI  - Functional and expression analysis of Arabidopsis SPA genes during seedling
      photomorphogenesis and adult growth.
AB  - The four members of the Suppressor of phyA-105 (SPA) gene family function to
      inhibit photomorphogenesis in dark- and light-grown seedlings. Additionally, SPA1
      SPA4 regulate elongation growth of adult plants. In these processes, SPA2, SPA3
      and SPA4 have overlapping but distinct functions. Here, we have further
      investigated the role of SPA1 which is partially masked by functional redundancy.
      We show that SPA1 represses not only red, far-red and blue light responses in a
      PHYA-dependent fashion, but also acts to suppress light signaling in darkness. We
      demonstrate that deletion-derivatives of SPA1 lacking the complete N-terminus or
      part of the kinase-like domain retain SPA1 function in light- and dark-grown
      seedlings, while deletion of the constitutive photomorphogenesis 1 (COP1)
      interacting coiled-coil domain eliminates SPA1 activity. This suggests that the
      coiled-coil domain and the WD-repeat domain of SPA1 are sufficient for SPA1
      function. An analysis of spa2 spa3 spa4 triple mutants demonstrates that SPA1,
      like SPA2, is sufficient for normal etiolation of dark-grown seedlings. In light
      grown seedlings and adult plants, in contrast, SPA1 function is divergent from
      SPA2 function, with SPA1 playing the predominant role. Levels of SPA1, SPA3 and
      SPA4 transcript are increased by red, far-red and blue light, consistent with a
      role of these three SPA genes in light-grown seedlings. The abundance of SPA2
      mRNA, in contrast, is not altered by light. Taken together, the analysis of SPA
      transcript levels suggests that differences in SPA gene expression patterns
      contribute to divergence in SPA1-SPA4 function.

PMID- 16813572
TI  - The central coiled-coil domain and carboxyl-terminal WD-repeat domain of
      Arabidopsis SPA1 are responsible for mediating repression of light signaling.
AB  - Arabidopsis constitutive photomorphogenic 1 (COP1) is an E3 ubiquitin ligase that
      directly binds and targets for degradation a number of photomorphogenesis
      promoting transcription factors, including HY5 and HFR1, to desensitize light
      signaling. Arabidopsis suppressor of phyA-105 (SPA1), which encodes a protein
      structurally related to COP1, also acts to repress photomorphogenesis under
      various light conditions. Here we show that overexpression of Arabidopsis SPA1
      results in a hyperetiolation phenotype and reduced accumulation of HY5 and HFR1.
      In addition, we show that both COP1 and SPA1 are each dependent on the presence
      of the other for their repressive effect on light signaling. Moreover, we
      demonstrate that both the central coiled-coil and the C-terminal WD-repeat
      domains of SPA1 are necessary, and together these two domains are sufficient for
      repressing photomorphogenesis. However, the N-terminal kinase-like domain of SPA1
      contributes to its full activity and promotes destabilization of the SPA1
      protein. Together, our results substantiate the notion that COP1 and SPA1 act in
      concert to form a functional E3 ubiquitin ligase complex and provide a molecular
      basis for understanding the structure-function relationship of SPA1.

PMID- 16813573
TI  - The Arabidopsis pex12 and pex13 mutants are defective in both PTS1- and PTS2
      dependent protein transport to peroxisomes.
AB  - Peroxisome biogenesis requires various complex processes including organelle
      division, enlargement and protein transport. We have been studying a number of
      Arabidopsis apm mutants that display aberrant peroxisome morphology. Two of these
      mutants, apm2 and apm4, showed green fluorescent protein fluorescence in the
      cytosol as well as in peroxisomes, indicating a decrease of efficiency of
      peroxisome targeting signal 1 (PTS1)-dependent protein transport to peroxisomes.
      Interestingly, both mutants were defective in PTS2-dependent protein transport.
      Plant growth was more inhibited in apm4 than apm2 mutants, apparently because
      protein transport was more severely decreased in apm4 than in apm2 mutants. APM2
      and APM4 were found to encode proteins homologous to the peroxins PEX13 and
      PEX12, respectively, which are thought to be involved in transporting matrix
      proteins into peroxisomes in yeasts and mammals. We show that APM2/PEX13 and
      APM4/PEX12 are localized on peroxisomal membranes, and that APM2/PEX13 interacts
      with PEX7, a cytosolic PTS2 receptor. Additionally, a PTS1 receptor, PEX5, was
      found to stall on peroxisomal membranes in both mutants, suggesting that PEX12
      and PEX13 are components that are involved in protein transport on peroxisomal
      membranes in higher plants. Proteins homologous to PEX12 and PEX13 have
      previously been found in Arabidopsis but it is not known whether they are
      involved in protein transport to peroxisomes. Our findings reveal that APM2/PEX13
      and APM4/PEX12 are responsible for matrix protein import to peroxisomes in
      planta.

PMID- 16813574
TI  - A trial of phenome analysis using 4000 Ds-insertional mutants in gene-coding
      regions of Arabidopsis.
AB  - Mutant lines covering all Arabidopsis genes allow us to pursue systematic
      functional genomics. A comprehensive phenotype description, called a phenome, is
      highly sought after in the profiling of -omics data. We selected 4000 transposon
      insertional lines with transposon insertions in their gene-coding regions, and
      systematically observed the visible phenotype of each line. For the first 3 weeks
      after germination, plants were grown on agar plates and the juvenile phenotypes
      were recorded. Then the plants were transferred to soil and their phenotypes were
      recorded at each growth stage. About 140 lines showed clear and reproducible
      visible phenotypes, including novel phenotypic mutants as well as previously
      reported ones. All descriptions of the mutants showing visible phenotypes were
      classified into eight primary categories (seedling, leaves, flowering and growth,
      stems, branching, flowers, siliques and seed yield) and 43 secondary categories
      of morphological phenotypes. Phenotypic images have been entered into a
      searchable database (http://rarge.gsc.riken.jp/phenome/). One example
      investigated through the use of plural alleles was a mutant of a novel gene
      related to glycerolipid biosynthesis, with a unique visible phenotype of sepal
      opening. Our results suggest that we can find more novel visible phenotypes and
      their corresponding genes, and that phenotypic mutants of gene knockouts are not
      exhausted yet. This study provides basic data on large-scale phenotyping of gene
      knockout lines in plants, and will contribute to the completion of an
      international effort to develop a phenome database of all the functional genes in
      Arabidopsis.

PMID- 16813575
TI  - A C2H2-type zinc finger protein, SGR5, is involved in early events of
      gravitropism in Arabidopsis inflorescence stems.
AB  - Plants can sense the direction of gravity and change the growth orientation of
      their organs. To elucidate the molecular mechanisms of gravity perception and the
      signal transduction of gravitropism, we have characterized a number of shoot
      gravitropism (sgr) mutants of Arabidopsis. The sgr5-1 mutant shows reduced
      gravitropism in the inflorescence stem but its root and hypocotyl have normal
      gravitropism. SGR5 encodes a zinc finger protein with a coiled-coil motif. The
      SGR5-GFP fusion protein is localized in the nucleus of Arabidopsis protoplasts,
      suggesting that SGR5 may act as a transcription factor. Analysis of GUS
      expression under the control of the SGR5 promoter revealed that SGR5 is mainly
      expressed in the endodermis, the gravity-sensing tissue in inflorescence stems.
      Furthermore, the observation that endodermis-specific expression of SGR5 using
      the SCR promoter in the sgr5-1 mutant restores shoot gravitropism indicates that
      it could function in the gravity-sensing endodermal cell layer. In contrast to
      other sgr mutants reported previously, almost all amyloplasts in the endodermal
      cells of the sgr5-1 mutant sedimented in the direction of gravity. Taken
      together, our results suggest that SGR5 may be involved in an early event in
      shoot gravitropism such as gravity perception and/or a signaling process
      subsequent to amyloplast sedimentation as a putative transcription factor in
      gravity-perceptive cells.

PMID- 16813576
TI  - Arabidopsis MAP kinase 4 regulates salicylic acid- and jasmonic acid/ethylene
      dependent responses via EDS1 and PAD4.
AB  - Arabidopsis MPK4 has been implicated in plant defense regulation because mpk4
      knockout plants exhibit constitutive activation of salicylic acid (SA)-dependent
      defenses, but fail to induce jasmonic acid (JA) defense marker genes in response
      to JA. We show here that mpk4 mutants are also defective in defense gene
      induction in response to ethylene (ET), and that they are more susceptible than
      wild-type (WT) to Alternaria brassicicola that induces the ET/JA defense
      pathway(s). Both SA-repressing and ET/JA-(co)activating functions depend on MPK4
      kinase activity and involve the defense regulators EDS1 and PAD4, as mutations in
      these genes suppress de-repression of the SA pathway and suppress the block of
      the ET/JA pathway in mpk4. EDS1/PAD4 thus affect SA-ET/JA signal antagonism as
      activators of SA but as repressors of ET/JA defenses, and MPK4 negatively
      regulates both of these functions. We also show that the MPK4-EDS1/PAD4 branch of
      ET defense signaling is independent of the ERF1 transcription factor, and use
      comparative microarray analysis of ctr1, ctr1/mpk4, mpk4 and WT to show that MPK4
      is required for induction of a small subset of ET-regulated genes. The regulation
      of some, but not all, of these genes involves EDS1 and PAD4.

PMID- 16813577
TI  - Arabidopsis cpFtsY mutants exhibit pleiotropic defects including an inability to
      increase iron deficiency-inducible root Fe(III) chelate reductase activity.
AB  - All plants, except for the grasses, must reduce Fe(III) to Fe(II) in order to
      acquire iron. In Arabidopsis, the enzyme responsible for this reductase activity
      in the roots is encoded by FRO2. Two Arabidopsis mutants, frd4-1 and frd4-2, were
      isolated in a screen for plants that do not induce Fe(III) chelate reductase
      activity in their roots in response to iron deficiency. frd4 mutant plants are
      chlorotic and grow more slowly than wild-type Col-0 plants. Additionally, frd4
      chloroplasts are smaller in size and possess dramatically fewer thylakoid
      membranes and grana stacks when compared with wild-type chloroplasts. frd4 mutant
      plants express both FRO2 and IRT1 mRNA normally in their roots under iron
      deficiency, arguing against any defects in systemic iron-deficiency signaling.
      Further, transgenic frd4 plants accumulate FRO2-dHA fusion protein under iron
      deficient conditions, suggesting that the frd4 mutation acts post-translationally
      in reducing Fe(III) chelate reductase activity. FRO2-dHA appears to localize to
      the plasma membrane of root epidermal cells in both Col-0 and frd4-1 transgenic
      plants when grown under iron-deficient conditions. Map-based cloning revealed
      that the frd4 mutations reside in cpFtsY, which encodes a component of one of the
      pathways responsible for the insertion of proteins into the thylakoid membranes
      of the chloroplast. The presence of cpFtsY mRNA and protein in the roots of wild
      type plants suggests additional roles for this protein, in addition to its known
      function in targeting proteins to the thylakoid membrane in chloroplasts.

PMID- 16813578
TI  - UPF1 is required for nonsense-mediated mRNA decay (NMD) and RNAi in Arabidopsis.
AB  - Aberrant mRNAs containing premature termination codons (PTCs) have the potential
      to be translated into truncated proteins, which could act to the detriment of the
      organism by interfering with normal cellular processes. Eukaryotes have
      mechanisms of mRNA quality control that identify PTC-containing transcripts and
      target them for destruction, a process known as nonsense-mediated mRNA decay
      (NMD). Surprising differences have been reported in the mechanisms of NMD between
      different organisms. UPF1 and UPF3 are structurally unrelated proteins, which
      function in the NMD pathway in yeast, mammals, Drosophila and Caenorhabditis
      elegans. Here we show that NMD in plants requires UPF1, as mRNAs containing PTCs
      become stabilized in upf1-5 mutants. However, in contrast to NMD in mammals, UPF1
      dependent NMD is capable of targeting both spliced and unspliced PTC-containing
      mRNAs. An allelic series of upf1 mutants exhibits a range of unexpected
      vegetative and floral abnormalities, including jagged leaves, late flowering,
      fused flowers and seedling lethality. We also show that mutants in UPF3 share
      these abnormalities. As both UPF1 and UPF3 are required for NMD, the similar
      phenotypes of the upf1 and upf3 mutants suggest that NMD regulates a common set
      of genes required for plant development and survival. Finally, gene silencing by
      an inverted repeat transgene is impaired in upf1-5 mutants, indicating a
      connection between UPF1 and RNA interference in plants.

PMID- 16813579
TI  - The role of phloem sieve elements and laticifers in the biosynthesis and
      accumulation of alkaloids in opium poppy.
AB  - The benzylisoquinoline alkaloids of opium poppy, including the narcotic
      analgesics morphine and codeine, accumulate in the multinucleate cytoplasm of
      specialized laticifers that accompany vascular tissues throughout the plant. In
      mature opium poppy plants, immunofluorescence labeling using specific antibodies
      showed that four alkaloid biosynthetic enzymes, (S)-norcoclaurine 6-O
      methyltransferase (6OMT), (S)-coclaurine N-methyltransferase (CNMT), (S)-3'
      hydroxy-N-methylcoclaurine-4'-O-methyltransferase (4'OMT) and salutaridinol-7-O
      acetyltransferase (SAT) were restricted to sieve elements of the phloem adjacent
      or proximal to laticifers. The identity of sieve elements was confirmed by (i)
      the specific immunogold labeling of the characteristic cytoplasm of this cell
      type, (ii) the co-localization of a sieve element-specific H(+)-ATPase with all
      biosynthetic enzymes and (iii) the strict association of sieve plates with
      immunofluorescent cells. The localization of laticifers was demonstrated
      antibodies specific to major latex protein (MLP), which is characteristic of this
      cell type. In situ hybridization using antisense RNA probes for 6OMT, CNMT, 4'OMT
      and SAT showed that the corresponding gene transcripts were found in the
      companion cell paired with each sieve element. Seven benzylisoquinoline alkaloid
      biosynthetic enzymes, (S)-N-methylcoclaurine 3'-hydroxylase (CYP80B1), berberine
      bridge enzyme, codeinone reductase, 6OMT, CNMT, 4'OMT and SAT were localized by
      immunofluorescence labeling to the sieve elements in the root and hypocotyl of
      opium poppy seedlings. The abundance of these enzymes increased rapidly between 1
      and 3 days after seed germination. The localization of seven biosynthetic enzymes
      to the sieve elements provides strong support for the unique, cell type-specific
      biosynthesis of benzylisoquinoline alkaloids in the opium poppy.

PMID- 16813582
TI  - The Pelican Cancer Foundation and The English National MDT-TME Development
      Programme.
AB  - The formation of The Pelican Cancer Foundation in 2000 was based around the
      pioneering work of Professor Bill Heald and colleagues, and the development of
      Total Mesorectal Excision (TME) for rectal cancer. A series of surgical workshops
      in Scandinavia in the mid 1990s and, later, six further workshops in the Trent
      region culminated in the commissioning of the fully multidisciplinary National
      MDT-TME Development Programme by the National Cancer Director, Professor Mike
      Richards, in March 2003.

PMID- 16813583
TI  - Complexities and controversies in the management of low rectal cancer:
      proceedings of the 3rd Pelican Surgical Symposium 2005.

PMID- 16813584
TI  - Defining the rectum: surgically, radiologically and anatomically.
AB  - The terminology used in relation to the rectum varies considerably, added to this
      there is the subjective nature of clinical assessment and variability in the
      anatomy of the rectum and anus. It is imperative that definitions are clarified
      and standardized for use by all members of the multidisciplinary team involved in
      the care of patients with rectal cancer.

PMID- 16813585
TI  - Magnetic resonance imaging of the low rectum: defining the radiological anatomy.
AB  - Low rectal cancer provides a particular surgical challenge of local tumour
      control and sphincter preservation. Histopathological studies have shown that an
      involved circumferential resection margin (CRM) and depth of extramural invasion
      are independent markers of poor prognosis and correlate with high local
      recurrence rates due to residual microscopic disease [1]. Recent data suggests
      that a CRM at risk of tumour involvement can be reliably seen on the pre
      operative magnetic resonance imaging (MRI) scan with good correlation with the
      histological specimen [2-5]. In published series, low rectal cancers have a
      higher incidence of involved resection margins, with rates up to 30% for abdomino
      perineal excision (APE) vs 10% for low anterior resection (LAR) [6-9]. This has
      been attributed to narrow surgical planes deep within the pelvis as the
      mesorectum becomes narrowed and tapered, forming a bare muscle tube at the level
      of the anal sphincter complex. The challenge for the surgeon is to undertake
      careful removal of a cylinder of tissue beyond the rectal wall without
      perforating the tumour. An overall local recurrence rate of 10% after APE for all
      stages of rectal cancer has been reported and this low rate was attributed to the
      surgical technique that included a wide peri-anal dissection and lateral division
      of the levator ani. The abdominal dissection was stopped above the tumour, taking
      care to avoid separation of the tumour from the levator ani to reduce the risk of
      inadvertent tumour cell spillage [8]. Therefore, rates of involved surgical
      margins from APE specimens may be reduced when a cuff of levators is taken
      compared with standard resection. In this review, we will discuss how MRI of the
      low rectum can aid in the staging and optimization of the best treatment strategy
      for low rectal cancer.

PMID- 16813586
TI  - Developments in the use of chemoradiotherapy in rectal cancer.
AB  - This paper reviews the current evidence available from phase III trials of
      combination pre-operative chemoradiotherapy (CRT) in the treatment of rectal
      cancer. There is clear evidence that CRT is superior to long-course radiotherapy
      (LRT). However, the end-points and definitions used must be standardized for
      future clinical trials of combination CRT.

PMID- 16813587
TI  - Emerging therapies for rectal cancer.
AB  - Preoperative treatment with either short-course radiotherapy or chemo
      radiotherapy (CRT) is used routinely in some centres to reduce local recurrence
      rates in patients with operable rectal cancer prior to optimal surgery. However,
      there is a need for new treatment strategies to further improve the outcomes of
      these patients, particularly with regard to survival. Advances in the treatment
      of metastatic disease, such as the use of combination chemotherapy with
      oxaliplatin and irinotecan, and the targeted agents bevacizumab and cetuximab,
      have led to clinical research into alternative radio-sensitizers during CRT and
      the novel use of neo-adjuvant (preoperative) chemotherapy prior to preoperative
      CRT and surgery. Whilst these remain experimental, it is likely that these will
      serve as a platform for developing an expanded range of treatment options so that
      clinicians will be better able to tailor treatment to the needs of different
      patients.

PMID- 16813588
TI  - Assessment and management of the complete clinical response of rectal cancer to
      chemoradiotherapy.
AB  - Preoperative chemoradiotherapy is considered by many as the preferred treatment
      strategy for distal rectal cancer. The observation of complete tumour regression
      has led to the proposition of nonoperative management of selected patients with
      complete clinical response (cCR) following treatment. We present results for the
      treatment of distal rectal cancer during 1991-2005. We have outlined the issues
      concerning adequate tumour assessment, the definition of complete response, and
      the advantages and disadvantages of conservative or surgical resection in
      patients with clinical and radiological evidence of cCR.

PMID- 16813589
TI  - The need for future surgical low rectal cancer studies.
AB  - Optimal surgery remains the mainstay of best outcome for rectal cancer. The
      demonstration, during the 3rd Annual Pelican Surgical Workshop Symposium, of an
      abdomino-perineal excision (APE) performed in the 'Berlin position', further
      added to the debate on optimal surgical technique. Much interest was created at
      the 1st Pelican symposium with the demonstration, by the Swedish surgeon Dr
      Torbjorn Holm, of a prone APE and the delivery of a 'cylindrical' specimen and
      the potential to reduce local recurrence using this approach. The high rates of
      local recurrence following APE and the discussions as to optimal technique have
      led to the development of a proposed MERCURY Study Group study to assess the
      benefit of a radical APE, with careful assessment of the impact that this
      operation may have on morbidity. A German study has also been proposed adopting
      the UK's multidisciplinary team approach. It aims at targeting preoperative
      chemoradiotherapy at those patients in whom a radical APE or total mesorectal
      excision is likely to result in an involved surgical resection margin. In this
      article we review the evidence for improving the surgical technique for low
      rectal cancer. We believe improvements may be best achieved through continued
      European prospective, multi-centre, multidisciplinary studies.

PMID- 16813590
TI  - A personal view on laparoscopic rectal cancer surgery.
AB  - Benefits such as reduced morbidity and shorter length of stay have been
      demonstrated for laparoscopic colon cancer resection, Laparoscopic rectal cancer
      surgery is thought to be more challenging and it is not clear if it offers the
      same benefits. There are concerns about oncological outcome and anastomotic
      technique and complications. In this review we discuss the difficulties and
      challenges of laparoscopic rectal cancer surgery within the context of our own
      personal experience and with regard to some of the current literature. We propose
      that laparoscopic and open rectal cancer surgery both have a role and the
      challenge is selection of appropriate patients for each technique.

PMID- 16813591
TI  - Laparoscopic surgery for colorectal cancer.
AB  - Traditionally open surgical resection has been recommended for colorectal
      tumours, but recently, laparoscopic surgery has gained popularity. This review
      summarizes the published data on laparoscopic colorectal cancer surgery with
      emphasis on recently published trials. For colon cancer laparoscopic resection
      appears to be associated with the same outcome as open surgery. However, whilst
      short-term outcome was better in the laparoscopic group in most of the randomized
      trials, when comparing laparoscopic with fast-track open surgery, no differences
      could be demonstrated in a randomized control trial. For rectal cancer the data
      are less clear. It seems that it may be feasible to resect at least small rectal
      cancers laparoscopically. Clearly the role of the laparoscopic technique needs to
      be better defined in rectal cancer. It has been well documented that short- and
      long-term outcome of colorectal cancer surgery depends on the quality and
      experience of the team treating the patient. Therefore, the major future
      challenge in laparoscopic colorectal cancer surgery will be to provide and
      structure adequate training and introduce quality control measures.

PMID- 16813592
TI  - Pathological assessment of rectal carcinoma after preoperative therapy.
AB  - Increasingly neoadjuvant therapy is being used to improve outcomes in patients
      with rectal carcinoma in which the circumferential resection margins are
      considered to be at risk for involvement if primary surgery were to be
      undertaken. Assessment of the response to this approach relies on radiological
      examination, particularly magnetic resonance imaging (MRI) studies. Following
      definitive surgery, careful histological examination allows full assessment of
      the tumour response to these preoperative approaches. Histological examination
      requires careful fixation, examination of the entire area occupied by the tumour
      prior to down-staging and careful lymph node harvesting. Adequate fixation helps
      in these endeavours and the lymph node harvest appears to be unaffected by
      neoadjuvant chemo- or radiotherapy. Correlation between preoperative assessment
      of response by MRI and the subsequent histological assessment is close, but the
      presence of isolated residual neoplastic glands in a post-treatment fibrotic
      stroma is impossible to detect prior to resection. The clinical significance of
      these microscopic foci remains uncertain, particularly in view of the prolonged
      tumour doubling time associated with colorectal adenocarcinoma. The preoperative
      discussion with the patient requires a synthesis of their own scan results and
      the experience of detailed clinico-pathological studies. While MRI frequently
      predicts the presence or absence of residual tumour the possibility of under
      staging remains and this is of crucial importance if a 'watch and wait' policy is
      to be adopted following apparent complete clinical and radiological remission.
      The significance of potential residual microscopic disease in patients with
      apparent radiological complete remission needs further investigation but may need
      to be interpreted in individual patients in the context of overall life
      expectancy.

PMID- 16813593
TI  - Quality of life and sexual function following surgery for rectal cancer.
AB  - The last 20 years have seen enormous strides forward in the treatment of rectal
      cancer with the development of improved surgical technique, tumour staging,
      histopathological audit and multidisciplinary team (MDT) management with emphasis
      on improving survival and reducing local recurrence rates. However, each rectal
      cancer discussed at the MDT meeting involves an individual patient. The quality
      of life for each patient must be taken into account when making treatment
      decisions, which sometimes may not fit with 'standard' treatment guidelines as
      the individual patient does not have a 'standard' tumour. For one patient with a
      tumour 5 cm above the anal verge, a low anterior resection may maintain quality
      of life with no incontinence and preservation of urinary and sexual function. For
      another with a tumour at the same level, preoperative chemo-radiotherapy may
      exacerbate mild incontinence and a low resection may result in a 'perineal
      stoma'. A decision to perform an abdomino-perineal excision (APE) must not be
      considered a failure of surgical treatment or be seen as a suboptimal centre by
      having a high APE rate. On the contrary, APE rates should represent sub
      specialization and patient selection. Indeed, good function from a permanent
      stoma may be better than bad function from a poorly functioning coloanal pouch.
      Having improved tumour staging, surgical technique, oncological treatment and
      histopathological assessment, quality of life must not be forgotten. Both quality
      and quantity of life are important to all patients.

PMID- 16813594
TI  - Extended surgery for local recurrence and advanced rectal cancer.
AB  - Although much effort has been directed at reducing the incidence of local
      recurrence after surgical resection of rectal cancer, there remain a significant
      number of patients who will develop local recurrence without evidence of
      metastatic disease. Such patients, as well as patients with locally advanced
      rectal cancer at presentation, may represent a surgical challenge. Application of
      sound surgical principals and team work can lead to a good long term outcome.
      This paper sets out to discuss the philosophy and techniques involved in the
      surgical management of such patients.

PMID- 16813595
TI  - Neurofibromin: a general outlook.
AB  - Neurofibromin is a cytoplasmic protein that is predominantly expressed in
      neurons, Schwann cells, oligodendrocytes, astrocytes and leukocytes. It is
      encoded by the gene NF1, located on chromosome 17, at q11.2, and has different
      biochemical functions, including association to microtubules and participation in
      several signaling pathways. Alterations in this protein are responsible for a
      phacomatosis named neurofibromatosis type 1.

PMID- 16813599
TI  - Association of lipoprotein lipase S447X, apolipoprotein E exon 4, and apoC3 
      455T>C polymorphisms on the susceptibility to diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. In DN
      patients, triglyceride (TG) level is elevated and lipoprotein lipase (LPL)
      activity, which hydrolyzes TG, is decreased. The LPL S447X and apolipoprotein E
      (APOE) exon 4 polymorphisms affect TG levels, and the APOC3 -455T>C polymorphism
      affects LPL activity. Our aim was to examine the association of these
      polymorphisms with nephropathy in type 2 diabetes. We examined these
      polymorphisms in a case-control study of type 2 diabetic patients including 374
      with DN and 392 without DN. LPL 447X-containing genotypes (447X+) were
      significantly decreased in DN patients [18.6 vs 25.6%, odds ratio (OR) = 0.66, p
      = 0.02], as were APOE epsilon3/epsilon3 genotypes (64.8 vs 73.1%, OR = 0.68, p =
      0.01). In addition, combinations of genotypes [APOE epsilon3/epsilon3 and LPL
      447X+ (OR = 0.56), APOC3 CC and LPL 447X+ (OR = 0.31), APOE epsilon3/epsilon3 and
      APOC3 CC (OR = 0.61] were protective for DN compared with the most common
      combination of the respective polymorphisms. Our findings suggest the importance
      of interactions among lipid genes in modulating the risk of DN.

PMID- 16813600
TI  - Maternal origin of a novel C-terminal truncation mutation in CDKL5 causing a
      severe atypical form of Rett syndrome.
AB  - The CDKL5 gene has been implicated in infantile spasms and more recently in a
      Rett syndrome-like phenotype. We report a case of a young girl presenting
      generalized convulsions at 10 days of life. Subsequent mutation analysis by
      denaturing high-performance liquid chromatography of MECP2 and CDKL5 genes
      revealed heterozygosity for a c.47_48insAGG insertion in exon 1 of MECP2 and
      heterozygosity for a new nonsense mutation p.Q834X and a new missense variant
      p.V999M in the CDKL5 gene. Co-segregation analysis showed that the nonsense
      mutation was a de novo mutation and that the insertion and the missense variant
      were also found in the asymptomatic mother. In the absence of skewed X
      inactivation in the mother, it is likely that these last two variants are not
      pathogenic. Reverse transcription-polymerase chain reaction from lymphoblastoid
      cells of the patient showed only the transcript without the nonsense and missense
      variations suggesting decreased stability of mature mRNA by nonsense-mediated
      decay. These data also suggest an occurrence of the de novo mutation in maternal
      germ line cells. Moreover, this report reinforces the observation that the CDKL5
      phenotype overlaps with Rett syndrome and that CDKL5 gene analysis is recommended
      in females with a seizure disorder commencing in the first weeks of life.

PMID- 16813601
TI  - A novel mutation in the EIF2AK3 gene with variable expressivity in two patients
      with Wolcott-Rallison syndrome.
AB  - Mutations in the EIF2AK3 gene have been identified in patients with Wolcott
      Rallison syndrome - a rare autosomal recessive disorder associated with permanent
      neonatal insulin-dependent diabetes. Despite the fact that different mutations
      have been observed in every single unrelated case reported so far, most patients
      presented with similar characteristics, such as osteopenia, epiphyseal dysplasia
      as well as hepatic and/or renal dysfunction. The EIF2AK3 gene was analyzed using
      a PCR-based sequencing approach in two Wolcott-Rallison patients and their
      parents. We report two cases from different families carrying the same and novel
      truncating nonsense mutation in the EIF2AK3 gene that encodes the pancreatic
      eukaryotic initiation factor 2alpha kinase 3. This mutation clearly displays
      different clinical characteristics in the two patients we examined. Remarkably,
      the onset of diabetes was different for the two patients, and there was also
      heterogeneity in other clinical manifestations. These cases illustrate the
      important role of alternative pathways that could, to some extent, take over or
      supplement a defective metabolic pathway. This supports the idea that there is no
      simple relationship among clinical manifestations and EIF2AK3 mutations.

PMID- 16813602
TI  - A cryptic full mutation in a male with a classical fragile X phenotype.
AB  - Fragile X syndrome (FRX) is the most common inherited cause of mental retardation
      affecting approximately 1/4000 males and half as many females. Mosaicism has been
      reported in 12-41% of male cases. We present a 47-year-old male with the typical
      FRX phenotype referred for an evaluation of mental retardation and a psychiatric
      disorder. Analysis of the FMR-1 CGG repeat size was performed on peripheral blood
      by PCR and Southern blot analysis. The proband was shown to carry a premutation
      allele of 58 CGG repeats. Because of the compelling clinical phenotype, further
      testing was performed on DNA extracted from skin fibroblasts, which yielded a 500
      CGG repeat allele. Mosaic cases of FRX have been reported but rarely without
      detectable mosaicism in peripheral blood. Therefore, this case is atypical
      because of the striking differences in the results obtained for the two different
      cell types. We concur with others that testing of ectodermally derived tissues
      may provide improved diagnosis and perhaps better insight into the overall
      prognosis of the affected individual. This case demonstrates the need to consider
      further study on other tissues when there is a strong clinical suspicion of FRX.

PMID- 16813603
TI  - Is there an influence of X-chromosomal imprinting on the phenotype in Klinefelter
      syndrome? A clinical and molecular genetic study of 61 cases.
AB  - Studies on Turner syndrome suggested the presence of X-chromosomal-imprinted
      genes involved in social and verbal cognition. Imprinted genes on autosomes were
      shown to affect growth. Could imprinting of such genes on the X chromosome also
      influence psychomotor development and growth in men with Klinefelter syndrome
      (KS), who have a supernumerary X? We recorded anthropometric and psychomotor
      development parameters for 61 males with KS (age range 2-56 years). In 54 cases,
      we were able to assess intelligence quotient (IQ) and found that impaired speech 
      and motor developmental problems were reported significantly more often in the
      paternal X - than in the maternal X group (P = 0.02). We found some significant
      (P < 0.05) increased body size parameters in the paternal X group, which concurs
      with data reporting a growth promoting influence of paternally derived genes. Our
      results suggest X-chromosomal imprinting occurs in males with KS.

PMID- 16813604
TI  - Genetic association between endothelial nitric oxide synthase and Alzheimer
      disease.
AB  - Evidence suggests that vascular and inflammatory factors may be important in the
      etiology of Alzheimer disease (AD). The Glu/Glu genotype at the Glu298Asp variant
      of the endothelial nitric oxide synthase (NOS3) gene has been tested for
      association with AD in several Caucasian and Asian populations, with conflicting
      results. We tested the Glu298Asp variant for association in African American and
      Caucasian AD patients, unaffected siblings, and unrelated controls from the
      MIRAGE Study. To explore whether the inconsistent results in previous studies
      might be due to linkage disequilibrium with a polymorphism or haplotype not
      previously tested, we genotyped 10 additional NOS3 single nucleotide
      polymorphisms (SNPs) spanning 25.3 kb. Finally, we compiled results of previous
      studies of Glu298Asp using meta-analysis, to determine whether the aggregate
      studies support an association between Glu298Asp and AD. We found that the Glu298
      allele was associated with higher risk of AD in the MIRAGE African American (p =
      0.002) but not Caucasian (p = 0.9) groups. None of the additional SNPs were
      associated with AD in the Caucasians, whereas two showed evidence for association
      in the African Americans. The meta-analysis showed a small effect of the
      Glu298Asp GG genotype on AD risk across all studies (summary odds ratio = 1.15,
      95% confidence interval: 0.97-1.35) and significant heterogeneity of this
      association among studies (p = 0.02).

PMID- 16813605
TI  - Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor
      impairment and severe urogenital abnormalities in patients with ATRX syndrome.
AB  - Mutations in ATRX are associated with a wide and clinically heterogeneous
      spectrum of X-linked mental retardation syndromes. The ATRX protein, involved in
      chromatin remodelling, belongs to the family of SWI/SNF DNA helicases and
      contains a plant homeodomain (PHD)-like domain. To date, more than 60 different
      mutations have been reported in ATRX. One of them is recurrent and accounts for
      20% of all the reported mutations, whereas all others are private. Most mutations
      are clustered in the two major functional domains, the helicase and the PHD-like
      domain. So far, no clear genotype-phenotype correlation has been established,
      with exception to the rare truncating mutations located at the C-terminal part of
      the protein, which are consistently associated with severe urogenital defects. In
      this study, we report the molecular analysis performed in 16 families positive
      for ATRX. Our findings indicate that, in addition to the previously described
      mutation 'hotspot' in the PHD-like domain, two other protein sections emerge as
      minor 'hotspots' in the helicase region encoded by exons 18-20 and 26-29,
      respectively, gathering 33% of all described mutations. Additionally, based on
      the clinical data collected for 22 patients from the 16 families, we observe that
      mutations in the PHD-like domain produce severe and permanent psychomotor
      deficiency, usually preventing patients from walking, as well as constant
      urogenital abnormalities, while mutations in the helicase domain lead to delayed
      but correct psychomotor acquisitions together with mild or absent urogenital
      abnormalities. In summary, mutations in the helicase domain are associated with
      milder phenotypes than mutations in the PHD-like domain.

PMID- 16813606
TI  - A novel nonsense mutation in the EYA1 gene associated with branchio-oto
      renal/branchiootic syndrome in an Afrikaner kindred.
AB  - Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized
      by the associations of hearing loss, branchial arch defects and renal anomalies.
      Branchiootic (BO) syndrome is a related disorder that presents without the highly
      variable characteristic renal anomalies of BOR syndrome. Dominant mutations in
      the human homologue of the Drosophila eyes absent gene (EYA1) are frequently the
      cause of both BOR and BO syndromes. We report a South African family of Afrikaner
      descent with affected individuals presenting with pre-auricular abnormalities and
      either hearing loss or bilateral absence of the kidneys. Genetic analysis of the
      pedigree detected a novel EYA1 heterozygous nonsense mutation in affected family
      members but not in unaffected family members or a random DNA panel. Through
      mutational analysis, we conclude that this particular mutation is the cause of
      BOR/BO syndrome in this family as a result of a truncation of the EYA1 protein
      that ablates the critical EYA homologous region. To the best of our knowledge,
      this is the first case of BOR/BO syndrome reported in Africa or in those of the
      Afrikaner descent.

PMID- 16813607
TI  - Frequency and nature of hMSH6 germline mutations in Polish patients with
      colorectal, endometrial and ovarian cancers.

PMID- 16813608
TI  - Clinical and genetic variability of oculodentodigital dysplasia.

PMID- 16813609
TI  - Genetic knowledge among participants of a German pilot study on hemochromatosis
      screening.

PMID- 16813610
TI  - Cerebrospinal fluid levels of orexin-A are not a clinically useful biomarker for
      Huntington disease.

PMID- 16813611
TI  - Detection of a novel Alu-mediated BRCA1 exon 13 duplication in Chinese breast
      cancer patients and implications for genetic testing.

PMID- 16813612
TI  - Gonadal mosaicism in hereditary angioedema.

PMID- 16813613
TI  - Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent.

PMID- 16813614
TI  - Training in paediatric trauma: the problem of safer societies.

PMID- 16813615
TI  - Adherence to guidelines for prevention of postsplenectomy sepsis. Age and sex are
      risk factors: a five-year retrospective review.
AB  - BACKGROUND: Vaccination, education and use of long-term antibiotics are
      recommended in expert guidelines for the prevention of infectious complications
      after splenectomy. However, studies outside Australia have shown poor adherence
      to the guidelines. METHOD: The aim of this study was to determine overall
      adherence to the guidelines and to ascertain any independent risk factors for
      poor compliance with the guidelines. A retrospective review of hospital records
      between 1999 and 2004 was carried out. RESULTS: Indications for splenectomy of
      the 111 patients in this review included post-trauma (32), haematological (32),
      cancer surgery (24), iatrogenic (12) and others (11). On multivariable analysis,
      age was associated with a 28% less likelihood to receive education (odds ratio
      (OR) 0.72; 95% confidence interval (CI) 0.56-0.92; P = 0.009) and 36% less
      likelihood to receive long-term antibiotics (OR 0.64; 95% CI 0.52-0.80; P < or =
      0.001). Women were four times more likely to receive education (OR 4.03; 95% CI
      1.16-14.0; P = 0.028) and patients who had undergone splenectomy in 2004 were 22
      times more likely to have received education compared with those in 1999 (OR
      22.53; 95% CI 3.12-162.34; P = 0.002). CONCLUSION: Education for prevention of
      sepsis after splenectomy is poorly documented and may be incomplete. Older age
      and male sex are risk factors in non-adherence to guidelines for prevention of
      postsplenectomy sepsis. Strategies such as alert cards and information brochures
      may improve adherence to guidelines particularly in older patients.

PMID- 16813616
TI  - Randomized controlled trial comparing prolene hernia system and lichtenstein
      method for inguinal hernia repair.
AB  - BACKGROUND: There are no data regarding the long-term outcomes of prolene hernia
      system (PHS) mesh in the published reports. The aim of the study was to compare
      the short-term and long-term outcomes of the PHS mesh with the Lichtenstein mesh
      technique. METHODS: Sixty-four patients with inguinal hernia were randomized to
      undergo either a PHS or a Lichtenstein repair under local anaesthesia as a day
      case. Early outcome measures were duration of surgery, pain scores, analgesic
      requirements, time to return to work, driving and full activity. Long-term
      outcome measures were chronic groin pain and recurrence. RESULTS: Mean duration
      of surgery in the PHS group was 36 min (SD +/- 11) versus 34 min in the
      Lichtenstein group (SD +/- 8; P = 0.3). There was no significant difference in
      analgesic requirements (P = 0.65). Overall mean pain score was 3.5/10 versus
      2.5/10 (P = 0.1). Mean time to return to work was 42 versus 30 days (P = 0.3),
      returning to driving was 20 versus 14 days (P = 0.2) and full activity was 21
      versus 22 days (P = 0.8). Chronic groin pain developed in four patients in the
      PHS group (12.9%) and in five patients in the Lichtenstein group (15.1%; P >
      0.05). One patient developed recurrent herniation in the PHS group. The median
      follow up was 4.2 years (range, 4-4.6 years). Patient satisfaction was very high
      with both the techniques. CONCLUSION: There is no significant difference in the
      early and long-term outcomes between PHS and Lichtenstein hernia repairs. The PHS
      technique involving preperitoneal dissection is well tolerated and easy to carry
      out under local anaesthesia.

PMID- 16813617
TI  - Diaphragmatic hernias complicating pregnancy.
AB  - BACKGROUND: Diaphragmatic hernias complicating pregnancy are not a common problem
      but they can have catastrophic consequences. They can present to the surgeon as a
      life-threatening emergency or pose a management dilemma when detected
      incidentally. In this paper, recommendations for the management of non-hiatal
      maternal diaphragmatic hernias are made based on our experience and the available
      published reports. METHODS: The presentation, management and outcomes of a series
      of three recent cases are described. A review of all other reported cases of
      diaphragmatic hernias complicating pregnancy was also carried out. RESULTS: All
      three cases were emergency presentations in the third trimester of pregnancy,
      resulting from compression of thoracic contents. All cases required emergency
      laparotomy and one also required thoracotomy. Delivery was by Caesarean section
      at the time of emergency surgery in two cases and was delayed in the third case.
      There was one fetal and no maternal deaths. One mother suffered persistent
      pleural infection. One baby also had a diaphragmatic hernia requiring postnatal
      repair. Published reports showed only 36 previously reported cases of
      diaphragmatic hernias identified in pregnancy. There is a consensus that hernias
      presenting with evidence of strangulation represent a surgical emergency and
      mandate operative management, irrespective of fetal maturity. Elective management
      of asymptomatic hernias is more controversial and both conservative and operative
      approaches have been suggested. CONCLUSION: Diaphragmatic hernias can cause life
      threatening complications in pregnancy. Consideration should be given to
      operative repair in the second trimester if asymptomatic hernias are identified
      during pregnancy. If vaginal delivery is attempted in the presence of a hernia,
      this should only be carried out under closely monitored conditions.

PMID- 16813618
TI  - Laparoscopic cardiomyotomy for achalasia: long-term outcomes.
AB  - BACKGROUND: Although the laparoscopic approach to oesophageal myotomy for
      achalasia is associated with reduced early postoperative morbidity compared with
      the open approach, most published reports describe relatively short-term follow
      up. For this reason, in a prospective cohort study, we determined the longer-term
      outcome for patients with uncomplicated achalasia who underwent a laparoscopic
      myotomy. In addition, we sought to identify preoperative factors predicting a
      good postoperative outcome. METHODS: The outcome for 167 patients who underwent a
      laparoscopic cardiomyotomy and anterior partial fundoplication at one of two
      teaching hospitals was determined. All patients underwent preoperative assessment
      with a contrast swallow radiology, gastroscopy and oesophageal manometry.
      Patients also underwent objective symptom evaluation before and after surgery
      using various outcome scales to determine dysphagia, reflux symptoms, side
      effects and overall satisfaction with the clinical outcomes. Patients were
      followed prospectively at yearly time points and data were managed on a
      computerized database. Postoperative objective investigations were undertaken if
      clinically indicated. RESULTS: Median operating time was 78 min (range, 30-210
      min). Most patients left the hospital within 72 h of surgery. Surgery was
      associated with a 5% complication rate and a 4% rate of conversion to open
      surgery. Five per cent of patients required a subsequent intervention during
      follow up. Over longer-term follow up (5 years or longer), 77% of patients had
      either no or minimal symptoms. At 1, 3 and 5 years, 96, 93 and 97% of patients
      indicated that they thought that they had made the correct decision to undergo
      surgery, although men consistently fared worse on their reported dysphagia
      outcome across a range of measures. CONCLUSION: Laparoscopic myotomy with
      anterior partial fundoplication achieves a good outcome for patients undergoing
      treatment of achalasia. Male patients do not perceive their outcome to be optimal
      in comparison with females but in the long term, they do not regret proceeding.

PMID- 16813619
TI  - Pancreaticoduodenectomy: does preoperative biliary drainage, method of pancreatic
      reconstruction or age influence perioperative outcome? A retrospective study of
      104 consecutive cases.
AB  - BACKGROUND: Whether preoperative biliary drainage (PBD) is beneficial in reducing
      complications after pancreaticoduodenectomy is controversial. There remains a
      reluctance to consider pancreaticoduodenectomy in older patients. The major
      source of morbidity and potential mortality after pancreaticoduodenectomy is
      pancreatic fistula, which is caused by difficulties associated with the
      pancreatic anastomosis. The purpose of this study was to examine the effect of
      PBD, patient age and method of pancreatico-enteric reconstruction on
      postoperative morbidity and mortality. METHODS: A total of 104 consecutive
      patients undergoing pancreaticoduodenectomy between November 1992 and November
      2004 were identified from a prospectively collected database. Multiple
      preoperative and intraoperative variables were examined and their relationship to
      postoperative outcome was analysed. RESULTS: Postoperative mortality was <1%.
      Forty-three patients (43%) suffered a total of 85 complications. Median length of
      stay was 12.5 days (range, 1-88 days). The group undergoing PBD did not have
      higher rates of infectious complication (12 vs 19%; P = 0.34) or overall
      complication (41 vs 42%; P = 0.88) compared with the undrained group. Rate of
      anastomotic leak (18 vs 4%; P = 0.045) and anaemia requiring transfusion (41 vs
      9%; P = 0.001) were significantly higher in the pancreaticojejunostomy group
      compared with the pancreaticogastrostomy group. Patients over the age of 70 years
      did not have higher rates of complication (44 vs 41%, P = 0.5) or postoperative
      length of stay. CONCLUSION: Preoperative biliary drainage was not associated with
      increased postoperative complications. Pancreaticogastrostomy after
      pancreaticoduodenectomy is a safe and reliable method of reconstruction. Finally,
      pancreaticoduodenectomy can be carried out with acceptable rates of postoperative
      morbidity and mortality in selected patients over 70 years of age.

PMID- 16813620
TI  - Questionnaire to aid priority and outcomes assessment in gallstone disease.
AB  - BACKGROUND: Limited health resources necessitate prioritization for access to
      elective cholecystectomy in New Zealand. We aimed to develop and validate a
      patient questionnaire for determining the effect of gallstone disease on quality
      of life (QOL) and evaluate its potential role in appraising prioritization and
      outcomes from surgery. METHODS: The Otago gallstones condition-specific
      questionnaire (CSQ) was designed based on review of published reports, structural
      equation modelling, input from experts and patient feedback. Fifty-four patients
      with symptomatic gallstone disease completed the CSQ including a single question
      asking about global condition impact, along with other QOL measures: the
      Gallstone Impact Checklist and the Short Form-36 Health Survey. Validity and
      reliability of the CSQ were assessed using standard psychometric criteria and
      patient acceptance was explored in a semistructured interview. Patients' priority
      status for surgery was determined by two participating surgeons and resulting
      scores were correlated with the QOL measures. RESULTS: Average CSQ completion
      time was 2.7 (range 1-5) min and patients found its content concise and
      comprehensive. Validity was supported through high correlations with the
      Gallstone Impact Checklist (r = 0.74), the global condition impact (r = 0.69) and
      related dimensions of the Short Form-36 Health Survey. CSQ questions showed
      satisfactory internal consistency (Cronbach's alpha = 0.94) and reproducibility
      (ICC = 0.93, where ICC is intraclass coefficient). Of all the QOL measures, the
      CSQ was the most clinically relevant, showing the strongest relationship with
      surgeon-rated priority (r = 0.62). CONCLUSION: Evidence is provided to support
      the validity of the CSQ for assessing the effect of gallstone disease on QOL. The
      CSQ could be particularly valuable in aiding priority decisions surgeons make and
      may be useful in tracking subsequent outcomes.

PMID- 16813621
TI  - Metastectomy for non-colorectal, non-neuroendocrine liver secondaries.
AB  - BACKGROUND: The role of metastectomy for colorectal and neuroendocrine liver
      secondaries is well established. Significant palliation and survival have been
      reported after aggressive surgical resection. However, the role of liver
      resection for secondaries from other primary tumours is less well defined. In
      this study, we aim to describe our experience, including indications and
      selection criteria, operative strategy and clinical outcome of liver resection,
      for non-colorectal, non-neuroendocrine liver metastases. METHODS: A review of
      prospectively collected operative database was conducted and patients who
      underwent liver resection of secondaries from non-colorectal, non-neuroendocrine
      primary tumours were studied. Eighteen patients were included in the study. There
      were 4 men and 14 women with a median age of 48 years (range, 37-78 years).
      RESULTS: Liver resection was carried out either for cure or for palliation of
      debilitating symptoms. Selection criteria included: (i) absence of extrahepatic
      disease and (ii) functional status of the liver and volume of remnant liver after
      hepatectomy. The median follow up was 24 months (range, 7-81 months) for 17
      patients, excluding the one who defaulted after surgery. Cancer-specific survival
      and recurrence-free interval was calculated from the date of hepatectomy. Liver
      resection was considered curative in 13 patients. There was no 30-day mortality
      in this cohort of patients. The median recurrence-free survival time was 13
      months (95% confidence interval (CI), 8-18 months). The median follow-up time for
      the 12 patients was 23.5 months (range, 7-35 months). Only five patients died due
      to cancer-specific causes and one died from acute myocardial infarction. The
      median cancer-specific survival time was 30 months (95% CI, 25-35 months). The 2
      year survival rate was 77.1% (95% CI, 48.9-100%). CONCLUSION: The results are
      encouraging and suggest that with appropriate selection criteria, there is a role
      for metastectomy of non-colorectal, non-neuroendocrine liver secondaries.

PMID- 16813622
TI  - Anastomotic leakage after lower gastrointestinal anastomosis: men are at a higher
      risk.
AB  - BACKGROUND: Anastomotic leakage is the most important complication specific to
      intestinal surgery. The aim of this study was to review the anastomotic leakage
      rates in a single Colorectal Unit and to evaluate the risk factors for
      anastomotic leakage after lower gastrointestinal anastomosis. METHODS: A total of
      541 consecutive operations involving anastomoses of the colon and rectum that
      were carried out between 1999 and 2004 at a single colorectal unit were reviewed.
      Data concerning 35 variables, relating to patient, tumour and surgical factors,
      were recorded. Outcomes with respect to anastomotic leakage and mortality were
      recorded. Data were analysed using univariate and multivariate analyses and odds
      ratios (OR) calculated. RESULTS: The overall rate of anastomotic leakage was 6.5%
      (35 of 541). The most frequently carried out operations were right hemicolectomy
      and anterior resection of the rectum, with leak rates of 2.2 and 7.4%,
      respectively. Univariate analysis showed that male gender (OR = 3.5), previous
      abdominal surgery (OR = 2.4), Crohn's disease (OR = 3.3), rectal cancer < or =12
      cm from the anal verge (OR = 5.4) and prolonged operating time (OR = 2.8) were
      factors significantly associated with anastomotic leakage. Male gender, a history
      of previous abdominal surgery and the presence of a low cancer remained
      significant after multivariate analysis. The risk of anastomotic leakage
      increased when two or more risk factors were present (P < 0.01). The overall
      mortality was 3.7% and was higher in patients with anastomotic leakage (14.3%; P
      = 0.01). CONCLUSIONS: Male gender, previous abdominal surgery and low rectal
      cancer are associated with increased anastomotic leakage rates. These have
      important implications during preoperative patient counselling and decision
      making regarding defunctioning stoma formation.

PMID- 16813623
TI  - New era: prophylactic surgery for patients with multiple endocrine neoplasia-2a.
AB  - BACKGROUND: The surgical management of patients with multiple endocrine neoplasia
      2A (MEN-2A) continues to evolve with specific genotype-phenotype correlations
      allowing for a more tailored approach. In this study, we report the surgical
      management of one of the largest MEN-2A families with a rearranged during
      transfection (RET) codon 804 mutation. METHOD: This is a cohort study comprising
      all at-risk kindred within a single known MEN-2A family. Prophylactic total
      thyroidectomy with lymph node dissection was recommended to all mutation carriers
      aged 5 years and older. RESULTS: There were a total of 48 at-risk individuals in
      the MEN-2A kindred, with 22 patients undergoing thyroidectomy after appropriate
      preoperative evaluation. A total of 9 patients had medullary thyroid cancer
      including 5 with a normal preoperative calcitonin level. A total of 11 patients
      had C-cell hyperplasia and 7 showed histological evidence of parathyroid disease.
      Only the index case had a phaeochromocytoma. CONCLUSIONS: Genetic testing for
      germline mutations in the RET proto-oncogene has allowed precise identification
      of affected RET carriers and provided the opportunity for prophylactic or
      'preclinical' surgery to treat and in fact to prevent medullary thyroid cancer.
      This concept of prophylactic surgery based on a genetic test is likely to be
      applied more widely as the tools of molecular biology advance.

PMID- 16813624
TI  - Margins and outcome of screen-detected breast cancer with extensive in situ
      component.
AB  - BACKGROUND: In situ disease surrounding invasive tumours is an important
      consideration in the management of patients with early breast cancer. This study
      of screen-detected breast cancers assessed the influence of in situ disease
      including an extensive in situ component (defined as ductal carcinoma in situ
      involving more than 25% of the area within the invasive tumour) on surgical
      management, local recurrence and survival of a group of patients. METHODS: A
      total of 595 cases of invasive breast cancer detected at St Vincent's
      BreastScreen were retrospectively reviewed to determine presence and extent of in
      situ disease, the surgical procedure and adequacy of excision. Outcome was
      examined in a cohort of 126 cases. RESULTS: A total of 438 (74%) patients had in
      situ foci in or around the invasive tumour and 107 (18%) were defined as
      extensive in situ component (EIC)-positive. The initial procedure was mastectomy
      in 20% of the cases and breast-conserving surgery in 80% including 18% who
      underwent further surgery. Re-excision (P = 0.02) or mastectomy (P = 0.01) was
      more often required in patients with EIC. After definitive local excision,
      margins were close or involved with invasive disease in 3% but the patients with
      EIC were more likely to have margins close or involved with in situ disease (16
      vs 2%; P = 0.001). There were seven deaths and one local invasive recurrence in
      the follow-up group and none of the deaths were in patients who were EIC
      positive. CONCLUSIONS: EIC predicts for a higher rate of re-excision and/or
      mastectomy. For patients with EIC, there is an acceptably low risk of local
      recurrence if margins are clear.

PMID- 16813625
TI  - Training in paediatric trauma: the problem of safer societies.
AB  - BACKGROUND: Trauma remains the most common cause of child death worldwide but the
      incidence of major trauma is declining in many developed countries: this has
      implications for training. METHODS: A survey of paediatric surgeons and
      paediatric surgical trainees was undertaken to evaluate perceptions of the
      relative importance of various forms of trauma training. A questionnaire was e
      mailed to Australasian paediatric surgeons and trainees to determine trauma
      courses they had undertaken, operative and non-operative paediatric trauma
      experience and attitudes towards trauma training. RESULTS: The overall response
      rate was 49% (40 of 83 consultants and 11 of 22 trainees). The Early Management
      of Severe Trauma course had been undertaken by 82% of consultants and all
      trainees. The Definitive Surgical Trauma Care course had been undertaken by 22%
      of consultants and one trainee. The number of trauma laparotomies carried out in
      the previous year was in the one to five range for 71% of responders. Greater
      emphasis was placed on the value of adult trauma experience by consultants who
      had a general surgical fellowship. CONCLUSION: In societies where major trauma in
      children is relatively rare (fortunately) and the opportunities for training are
      limited, it is important to ensure that advanced trainees in paediatric surgery
      gain sufficient skills from a variety of sources to enable them to treat
      competently the severely injured child with multiple injuries.

PMID- 16813626
TI  - Outcomes of patients with orthopaedic trauma admitted to level 1 trauma centres.
AB  - BACKGROUND: Although orthopaedic trauma results in significant disability and
      substantial financial cost, there is a paucity of large cohort studies that
      collectively describe the functional outcomes of a variety of these injuries. The
      current study aimed to investigate the outcomes of patients admitted with a range
      of orthopaedic injuries to adult Level 1 trauma centres. METHODS: Patients were
      recruited from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), which
      included all patients with orthopaedic trauma admitted to the two adult Level 1
      trauma centres in Victoria (Australia). Patients were categorised into three
      groups; isolated orthopaedic injuries, multiple orthopaedic injuries and
      orthopaedic and other injuries. Demographic and injury data were collected from
      the medical record and hospital/trauma databases, and functional outcome
      instruments were given at 6 months post-injury. RESULTS: Of the 1303 patients
      recruited for VOTOR over a 12-month period, 1181 patients were eligible for the
      study and a response rate of 75.6% was obtained at 6 months post-injury. Patients
      reported ongoing pain (moderate-severe: 37.2%), disability (79.5%) and inability
      to return to work (35.2%). Poorer outcomes were evident in patients with
      orthopaedic and other injuries than those with single or multiple orthopaedic
      injuries alone. CONCLUSION: A large percentage of patients have ongoing pain and
      disability and a reduced capacity to return to work 6 months after orthopaedic
      trauma. Further research into the long-term outcomes of patients with orthopaedic
      injuries is required to identify patient subgroups and specific injuries and
      procedures that result in high morbidity.

PMID- 16813627
TI  - No rest for the wounded: early ambulation after hip surgery accelerates recovery.
AB  - BACKGROUND: Level 3 evidence-based guidelines recommend first walk after hip
      fracture surgery within 48 h. Early mobilization is resource and effort intensive
      and needs rigorous investigation to justify implementation. This study uses a
      prospective randomized method to investigate the effect of early ambulation (EA)
      after hip fracture surgery on patient and hospital outcomes. METHODS: Sixty
      patients (41 women and 19 men; mean age 79.4 years) admitted between March 2004
      through December 2004 to The Alfred Hospital, Melbourne, for surgical management
      of a hip fracture were studied. Randomization was either EA (first walk
      postoperative day 1 or 2) or delayed ambulation (DA) (first walk postoperative
      day 3 or 4). Functional levels on day 7 post-surgery, acute hospital length of
      stay and destination at discharge were compared. RESULTS: At 1 week post-surgery,
      patients in the EA group walked further than those in the DA group (P = 0.03) and
      required less assistance to transfer (P = 0.009) and negotiate a step (P = 0.23).
      Patients in the EA group were more likely to be discharged directly home from the
      acute care than those in the DA group (26.3 compared with 2.4%) and less likely
      to need high-level care (36.8 compared with 56%). A failed early ambulation
      subgroup had significantly more postoperative cardiovascular instability and
      worse results for all outcome measures. CONCLUSION: EA after hip fracture surgery
      accelerates functional recovery and is associated with more discharges directly
      home and less to high-level care.

PMID- 16813628
TI  - Surgical management of extracranial internal carotid aneurysms by cervical
      approach.
AB  - BACKGROUND: Extracranial internal carotid artery aneurysms (EICAA) are rare
      vascular problems with a great potential for lethal thromboembolic episodes.
      METHODS: From 1994 to 2004, nine patients with EICAA, seven men and two women,
      were surgically treated for 10 aneurysms in our department. Aneurysm led to
      hemispheric symptoms in six cases (two hemispheric strokes and four hemispheric
      transient ischaemic attacks). The cause was fibrodysplasia in two cases,
      atherosclerosis in four cases, trauma in two cases and spontaneous dissection in
      two cases. All aneurysms were treated surgically by the cervical approach using
      shunting. Extended cervical approach was necessary in four patients with high
      lying aneurysms. Nine aneurysms were totally resected and successful
      revascularization was carried out. Open aneurysmorrhaphy with vein patch
      angioplasty was carried out in one case of a saccular aneurysm. RESULTS: There
      were no perioperative deaths or transient ischaemic attacks or strokes. Four
      patients developed cranial nerve deficits: one had hoarsness, two had partial
      facial paralysis (patients with extended cervical approach) and one had tongue
      deviation. These neurological symptoms were observed in large aneurysms (>4.5 cm)
      and disappeared within 14 months. No neurological complication was observed in a
      follow up that ranged from 6 months to 10 years. CONCLUSIONS: Surgical repair of
      EICAA, especially with total resection and arterial reconstruction, is strongly
      recommended. Extended cervical approach has many technical difficulties but can
      allow treatment of high-lying aneurysms.

PMID- 16813629
TI  - Assessing surgeons' disclosure of risk information before carotid endarterectomy.
AB  - BACKGROUND: To make an informed decision about treatment, patients need accurate
      information about the benefits and risks of treatment and 'non-treatment'
      options. A survey was conducted to determine patients' recall of the extent and
      effect of preoperative disclosure by surgeons to patients of risks about carotid
      endarterectomy (CEA). METHODS: A self-administered questionnaire was given to 133
      patients undergoing elective CEA in New South Wales. The primary outcome measures
      were patient recall of preoperative discussion, self-assessed estimates of stroke
      risk with and without surgery and receipt of written information before CEA.
      RESULTS: A significantly higher proportion of patients recalled that their
      surgeon discussed the short-term stroke risk (i.e. within 30 days) if they
      decided to undergo CEA (86.2%) than if they decided not to have the procedure
      (76.9%) (P = 0.04). Of those patients who recalled the surgeon discussing their
      short-term stroke risk with CEA, only 24 (18.0%) were accurately able to quantify
      this risk. Patients were significantly more likely to recall their surgeon
      discussing their long-term stroke risk (i.e. within 2 years) if they decided not
      to have CEA (72.4%) than if they decided to have the CEA (31.5%) (P < 0.0001).
      CONCLUSIONS: Patients recalled discussions with their surgeon about short-term
      stroke risk. Only a minority, however, accurately quantified their postoperative
      stroke risk. In view of variable patient recall, decision aids could assist.

PMID- 16813630
TI  - Potential effects of hyperbaric oxygen therapy in acute pancreatitis.
AB  - BACKGROUND: To extract from the biomedical published reports, the effects of
      hyperbaric oxygen (HBO) on inflammatory disease, in particular acute
      pancreatitis. METHODS: This review will explain these effects and evaluate
      potential mechanisms of action of HBO in acute pancreatitis. A Medline/PubMed
      search (January 1966 to July 2004) with manual cross-referencing was conducted,
      including all relevant articles investigating the molecular and systemic effects
      of HBO on inflammatory diseases, particularly focusing on the studies of acute
      pancreatitis. All publication types, languages and subsets were searched.
      RESULTS: Original and review articles and short communications were extracted.
      The selected original articles covered the molecular and systemic effects of HBO
      and the effects in inflammatory disease states. The major findings are that HBO
      can act as an anti-inflammatory agent and as an antimicrobial agent. Many of the
      effects of HBO would be beneficial in the treatment of acute severe pancreatitis.
      Work carried out to date in animal models of acute pancreatitis shows promising
      improvements in severity but studies are limited to date. CONCLUSION: Acute
      pancreatitis impairs the pancreatic and systemic microcirculation and causes
      acute inflammation. These processes are potentially improved by HBO therapy.

PMID- 16813631
TI  - Hepatocellular carcinoma presenting with obstructive jaundice.
AB  - BACKGROUND: Jaundice occurs in 5-44% of patients with hepatocellular carcinoma
      (HCC). It is an important clinical presentation as the different aetiological
      causes of jaundice in HCC determine the therapeutic approach and the prognosis.
      This article aims to review the classification, management and prognosis of
      patients with jaundice associated with HCC. METHODS: A Medline search was
      undertaken to identify articles using the key words 'hepatocellular carcinoma',
      'jaundice' and 'tumour thrombus'. Additional articles were identified by a manual
      search of the references from the key articles. RESULTS: Patients with jaundice
      due to hepatic parenchymal insufficiency (hepatocellular type) have a very dismal
      prognosis. For patients with biliary obstruction due to HCC (icteric type), the
      reported 1-, 3- and 5-year survival rates after curative resection were 57.1
      100%, 20-47% and 6.7-45%, respectively. The mean survival after palliative
      biliary drainage alone was less than 6 months but when biliary drainage was
      combined with other palliative treatment, the mean survival could be up to 1
      year. CONCLUSIONS: It is important to differentiate the hepatocellular type from
      the icteric type of HCC. For patients with the icteric type of HCC, curative
      liver resection can achieve a survival comparable to that in patients without
      jaundice. For patients with unresectable icteric type of HCC, treatment can
      provide improvement in patient's quality of life and survival.

PMID- 16813632
TI  - Terrorism and blast explosions: lessons for the Australian surgical community.
AB  - The prospect of a terrorist attack against Australian interests is currently
      being debated across our society. The explosive blast attack is most favoured by
      terrorists. Blast injuries create unique patterns of multisystem injury with
      contaminated wounds and extensive devitalized tissue. Australian civilian
      surgeons are increasingly likely to be involved in the management of these
      injuries, either in response to a terrorist incident in Australia or as part of
      delayed management of Australian nationals injured overseas. An appreciation of
      the unique complexities of blast injuries is equally important to both military
      and civilian surgeons. This paper covers the mechanisms and pathophysiology of
      blast injuries and discusses issues of surgical management as they would apply to
      an Australian civilian setting.

PMID- 16813633
TI  - Regulation of fibrogenesis during the early phase of common bile duct
      obstruction.
AB  - BACKGROUND: Both nitric oxide (NO) and prostaglandins have been proposed as
      inhibitor substances involved in collagen deposition in the hepatic parenchyma.
      The possible reciprocal connections between NO and eicosanoids in the development
      of liver fibrosis were investigated during the initial phase of common bile duct
      obstructions. METHODS: A total of 30 male albino guinea pigs were randomly and
      equally assigned to three groups. Group 1 underwent sham laparotomy. Group 2 and
      group 3 were subjected to permanent common bile duct ligature for 24 and 72 h,
      respectively. Changes in the liver prostaglandin E(2) (PGE(2)), leukotriene C(4),
      malondialdehyde contents and plasma nitrite plus nitrate concentrations were
      measured. To evaluate the extent of hepatic fibrosis, histological assessment of
      liver was confirmed with the equivalent hydroxyproline contents of liver.
      RESULTS: Twenty-four hours after ligature, the amount of malondialdehyde and
      PGE(2) and plasma nitrite plus nitrate concentrations increased significantly,
      whereas liver hydroxyproline contents did not change. However, 72 h after
      ligature (Group 3), lipid peroxidation and collagen deposition were significantly
      higher than that of the group 2 animals. The PGE(2) : leukotriene C(4) ratio
      peaked at 24 h and later decreased, whereas PGE(2) : NO ratio remained unchanged
      in both group 2 and group 3 animals. CONCLUSIONS: The initiation of collagen
      synthesis occurred in portal tract as early as within the first 72 h of bile duct
      obstruction. The optimum function of reactive oxygen species on the stellate cell
      activation might be determined by the interaction between NO and PGE(2).

PMID- 16813634
TI  - Localization of small pulmonary nodules for videothoracoscopic surgery.
AB  - The aim of this study is to discuss and summarize the localization of small
      pulmonary nodules for video-thoracoscopic surgery. Thirty-eight patients were
      selected, 22 men and 16 women, and they underwent video-assisted thoracoscopic
      surgery resection for small pulmonary nodules: 28 patients for small solitary
      pulmonary nodules and 10 patients for multiple small pulmonary nodules. In all
      cases, resection of the nodules was successful. Localization methods included:
      (i) computed tomography (CT)-guided methylene blue labelling for preoperative
      localization; (ii) a high-quality chest CT scan for preoperative localization;
      (iii) visual exploration, digital palpation and 'instrumental' palpation to
      locate the nodule; and (iv) endosonographic inspections of intraoperative
      localization. Using a combination of CT scan, digital palpation, methylene blue
      labelling and endosonographic inspections, all nodules were successfully
      localized and resected without significant complications. Video-assisted
      thoracoscopic surgery is an effective approach but the small lung nodules
      (especially those less than 1.0 cm in diameter) localized at thoracoscopic
      resection must be treated carefully. Combined imaging and thoracoscopic
      techniques may help identify small nodules.

PMID- 16813636
TI  - Medial pectoral pedicle: a critical landmark in axillary dissection.
AB  - Surgery for breast cancer has evolved over the last century and has gone from
      limited to radical, extended radical and back to conservative surgery. Along this
      journey, one constant feature has been the necessity for a complete axillary
      dissection. In recent times, this concept has also been successfully challenged
      and now we are in an era of conservative or limited surgery in the axilla as
      well. These surgical procedures such as four-node axillary sampling or the
      technology-driven sentinel node biopsy are conservative axillary procedures and
      are often performed through very small incisions. With limited access to the
      surgical field, there is always an increased chance of inadvertent and
      unnecessary injury to surrounding vital anatomical structures such as nerves or
      blood vessels. A well-designed road map can definitely prevent such mishaps. This
      paper describes a simple technique of axillary surgery, which is step-wise and
      makes use of a relatively constant landmark, namely the medial pectoral pedicle,
      present within the axilla. Such a regimented systematic approach not only allows
      us to minimize the risks of complications during axillary surgery, but also
      enables us to train beginners easily and efficiently.

PMID- 16813637
TI  - Fifty years of vascular surgery in australia and new zealand.
AB  - Over the 50 years that vascular surgery has been practised in Australia and New
      Zealand there have been major advances and refinements of surgical techniques,
      particularly with the advent of endovascular surgery, spurred on especially with
      the introduction of endovascular aortic aneurysm stent grafting. At the same
      time, there has been a revolution in medical imaging, with the introduction of
      ultrasound, computed tomography scanning and magnetic resonance scanning.
      Vascular surgery in Australia and New Zealand was initially an interest of either
      general or cardiothoracic surgeons, but was recognized as a subspecialty of
      general surgery with the formation of the Section of Vascular Surgery within the
      Division of General Surgery of the Royal Australasian College of Surgeons in
      1972. In 1981, a 2-year training programme in vascular surgery was established
      and in 1983 an Australian and New Zealand Chapter of the International Society
      for Cardiovascular Surgery was formed. In 1995, vascular surgery was recognized
      as a specialty in its own right with the formation of the Division of Vascular
      Surgery within the College. There has been a separate examination for Fellowship
      of the Royal Australasian College of Surgeons (Vascular) since 1997. In 2001, the
      Chapter changed its name to The Australian and New Zealand Society for Vascular
      Surgery and in 2002 it amalgamated with and took over the functions of the
      Division of Vascular Surgery, which was formally dissolved.

PMID- 16813638
TI  - Scedosporium prolificans: an uncommon cause of septic arthritis.
AB  - Septic arthritis due to fungal infection is uncommon, but when it does occur it
      can have a devastating effect. Scedosporium prolificans is an emerging fungal
      pathogen that appears to have a predilection for bone and cartilaginous surfaces.
      This fungus is resistant to most commonly prescribed antifungal agents. We report
      the successful treatment of Scedosporium prolificans septic arthritis with a
      combination of surgery and new antifungal agents.

PMID- 16813639
TI  - Hypertensive primary intraventricular hemorrhage due to a phaeochromocytoma.
AB  - Primary intraventricular haemorrhage (IVH) is rare. We defined primary IVH as
      haemorrhage into the ventricles only as detected by computerized tomographic (CT)
      brain scan. This is in contrast with other intracerebral haemorrhages (e.g. basal
      ganglia/thalamic with intraventricular extension). The clinical condition of the
      patient ranges from minimal neurological deficits to coma/death. It also carries
      with it a poor prognosis of up to 80% when all four ventricles are involved. We
      present a 45-year-old Chinese female who presented with a hypertensive IVH which
      was managed successfully with ventricular drainage and intraventricular urokinase
      therapy. An adrenal phaeochromocytoma was diagnosed which was subsequently
      removed laparoscopically. The patient has recovered well in all aspects. This
      case report will discuss management of IVH and the importance of searching for
      secondary causes of hypertension.

PMID- 16813640
TI  - Gluteal compartment syndrome.
AB  - Gluteal compartment syndrome is uncommon and is often diagnosed late, resulting
      in muscle necrosis and sciatic nerve palsy. The mainstay of treatment is prompt
      diagnosis and early surgery. A high index of suspicion is essential, especially
      in the setting of major bleeding and excessive pain. Embolization and hyperbaric
      oxygen may be considered as adjuncts to surgery.

PMID- 16813641
TI  - The influence of language spoken on colorectal cancer diagnosis and management.

PMID- 16813642
TI  - Surgical training: a change for the better.

PMID- 16813643
TI  - Bleeding after stapled haemorhoidopexy using PPH 03 instrument.

PMID- 16813644
TI  - Microarray MAPH: accurate array-based detection of relative copy number in
      genomic DNA.
AB  - BACKGROUND: Current methods for measurement of copy number do not combine all the
      desirable qualities of convenience, throughput, economy, accuracy and resolution.
      In this study, to improve the throughput associated with Multiplex Amplifiable
      Probe Hybridisation (MAPH) we aimed to develop a modification based on the 3
      Dimensional, Flow-Through Microarray Platform from PamGene International. In this
      new method, electrophoretic analysis of amplified products is replaced with
      photometric analysis of a probed oligonucleotide array. Copy number analysis of
      hybridised probes is based on a dual-label approach by comparing the intensity of
      Cy3-labelled MAPH probes amplified from test samples co-hybridised with similarly
      amplified Cy5-labelled reference MAPH probes. The key feature of using a
      hybridisation-based end point with MAPH is that discrimination of amplified
      probes is based on sequence and not fragment length. RESULTS: In this study we
      showed that microarray MAPH measurement of PMP22 gene dosage correlates well with
      PMP22 gene dosage determined by capillary MAPH and that copy number was
      accurately reported in analyses of DNA from 38 individuals, 12 of which were
      known to have Charcot-Marie-Tooth disease type 1A (CMT1A). CONCLUSION:
      Measurement of microarray-based endpoints for MAPH appears to be of comparable
      accuracy to electrophoretic methods, and holds the prospect of fully exploiting
      the potential multiplicity of MAPH. The technology has the potential to simplify
      copy number assays for genes with a large number of exons, or of expanded sets of
      probes from dispersed genomic locations.

PMID- 16813645
TI  - New paradigm in implant osseointegration.
AB  - During the last years, implant dentistry has seen an dramatic increase as a
      treatment option in oral rehabilitation. This is based to a large extent on
      scientific advances and clinical improvements in implantology. The extension of
      indications has broadened the opportunities to rehabilitate patients that were
      formerly considered to possess restricted indications to place implants.
      Additionally, patient desires (high aesthetic demands, fast prosthetic
      rehabilitation) were placed more in focus, resulting in new approaches in implant
      dentistry. As a result, the scientific and clinical community has reached high
      standards and at the same time has founded the basis for new opportunities in
      implantology. The advances are mirrored by a high number of high quality
      scientific papers, published in conventional and open-access journals. A major
      shift has thereby been observed in the understanding of implant healing, leading
      the basis for new implant systems that allow fast rehabilitation protocols. The
      term osseointegration needs a new understanding since an immediate
      osseointegration state can be present under distinct conditions.

PMID- 16813646
TI  - Evidence of structural genomic region recombination in Hepatitis C virus.
AB  - BACKGROUND/AIM: Hepatitis C virus (HCV) has been the subject of intense research
      and clinical investigation as its major role in human disease has emerged.
      Although homologous recombination has been demonstrated in many members of the
      family Flaviviridae, to which HCV belongs, there have been few studies reporting
      recombination on natural populations of HCV. Recombination break-points have been
      identified in non structural proteins of the HCV genome. Given the implications
      that recombination has for RNA virus evolution, it is clearly important to
      determine the extent to which recombination plays a role in HCV evolution. In
      order to gain insight into these matters, we have performed a phylogenetic
      analysis of 89 full-length HCV strains from all types and sub-types, isolated all
      over the world, in order to detect possible recombination events. METHOD:
      Putative recombinant sequences were identified with the use of SimPlot program.
      Recombination events were confirmed by bootscaning, using putative recombinant
      sequence as a query. RESULTS: Two crossing over events were identified in the
      E1/E2 structural region of an intra-typic (1a/1c) recombinant strain. CONCLUSION:
      Only one of 89 full-length strains studied resulted to be a recombinant HCV
      strain, revealing that homologous recombination does not play an extensive roll
      in HCV evolution. Nevertheless, this mechanism can not be denied as a source for
      generating genetic diversity in natural populations of HCV, since a new intra
      typic recombinant strain was found. Moreover, the recombination break-points were
      found in the structural region of the HCV genome.

PMID- 16813647
TI  - Reference values for exhaled nitric oxide (reveno) study.
AB  - BACKGROUND: Despite the widespread use of fractional exhaled nitric oxide (FENO)
      as a biomarker of airways inflammation, there are no published papers describing
      normal FENO values in a large group of healthy adults. OBJECTIVE: The aim of this
      study was to establish adult FENO reference values according to the international
      guidelines. METHODS: FENO was measured in 204 healthy, non-smoking adults with
      normal spirometry values using the on-line single-breath technique, and the
      results were analysed chemiluminescently. RESULTS: The main result of the study
      was the significant difference in FENO values between men and women, thus
      indicating that gender-based reference FENO values are necessary. The FENO levels
      obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and
      from 1.6 to 21.5 ppb in women. CONCLUSION: We propose reference FENO values for
      healthy adult men and women that could be used for clinical and research
      purposes.

PMID- 16813648
TI  - Dopamine presynaptically and heterogeneously modulates nucleus accumbens medium
      spiny neuron GABA synapses in vitro.
AB  - BACKGROUND: The striatal complex is the major target of dopamine action in the
      CNS. There, medium-spiny GABAergic neurons, which constitute about 95% of the
      neurons in the area, form a mutually inhibitory synaptic network that is
      modulated by dopamine. When put in culture, the neurons reestablish this network.
      In particular, they make autaptic connections that provide access to single,
      identified medium-spiny to medium-spiny neuron synaptic connections. RESULTS: We
      examined medium-spiny neuron autaptic connections in postnatal cultures from the
      nucleus accumbens, the ventral part of the striatal complex. These connections
      were subject to presynaptic dopamine modulation. D1-like receptors mediated
      either inhibition or facilitation, while D2-like receptors predominantly mediated
      inhibition. Many connections showed both D1 and D2 modulation, consistent with a
      significant functional colocalization of D1 and D2-like receptors at presynaptic
      sites. These same connections were subject to GABAA, GABAB, norepinephrine and
      serotonin modulation, revealing a multiplicity of modulatory autoreceptors and
      heteroreceptors on individual varicosities. In some instances, autaptic
      connections had two components that were differentially modulated by dopamine
      agonists, suggesting that dopamine receptors could be distributed heterogeneously
      on the presynaptic varicosities making up a single synaptic (i.e. autaptic)
      connection. CONCLUSION: Differential trafficking of dopamine receptors to
      different presynaptic varicosities could explain the many controversial studies
      reporting widely varying degrees of dopamine receptor colocalization in medium
      spiny neurons, as well as more generally the diversity of dopamine actions in
      target areas. Longer-term changes in the modulatory actions of dopamine in the
      striatal complex could be due to plasticity in the presynaptic distribution of
      dopamine receptors on medium-spiny neuron varicosities.

PMID- 16813649
TI  - Migratory marker expression in fibroblast foci of idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Fibroblast foci (FF) are considered a relevant morphologic marker of
      idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), and are
      recognised as sites where fibrotic responses are initiated and/or perpetuated in
      this severe disease. Despite their relevance, the cellular and molecular
      mechanisms responsible for the formation of FF and their role in tissue
      remodelling are poorly defined. In previous studies we have provided evidence of
      abnormal activation of the wnt-signaling-pathway in IPF/UIP that is centred on FF
      and the overlying epithelium. This important morphogenetic pathway is able to
      trigger epithelial-mesenchymal-transition (EMT), a mechanism involved in
      developmental and metastatic processes, which is also potentially involved in
      pulmonary fibrosis. METHODS: Since EMT is characterised by enhancement of
      migratory potential of cells, we investigated the molecular profile of FF in 30
      biopsies of IPF/UIP and a variety of control samples, focussing on the
      immunohistochemical expression of three molecules involved in cell motility and
      invasiveness, namely laminin-5-gamma2-chain, fascin, and heat-shock-protein-27.
      RESULTS: We provide evidence that in UIP these three molecules are abnormally
      expressed in discrete clusters of bronchiolar basal cells precisely localised in
      FF. These cellular clusters expressed laminin-5-gamma2-chain and heat-shock
      protein-27 at very high levels, forming characteristic three-layered lesions
      defined as "sandwich-foci" (SW-FF). Upon quantitative analysis SW-FF were present
      in 28/30 UIP samples, representing more than 50% of recognisable FF in 21/30, but
      were exceedingly rare in a wide variety of lung pathologies examined as controls.
      In UIP, SW-FF were often observed in areas of microscopic honeycombing, and were
      also found at the interface between normal lung tissue and areas of dense
      scarring. CONCLUSION: These molecular abnormalities strongly suggest that SW-FF
      represent the leading edge of pulmonary remodelling, where abnormal migration and
      re-epithelialisation take place, and that abnormal proliferation and migration of
      bronchiolar basal cells have a major role in the remodelling process
      characterising IPF/UIP. Further investigations will assess their possible use as
      reliable markers for better defining the UIP-pattern in difficult cases.

PMID- 16813650
TI  - Anticancer drug clustering in lung cancer based on gene expression profiles and
      sensitivity database.
AB  - BACKGROUND: The effect of current therapies in improving the survival of lung
      cancer patients remains far from satisfactory. It is consequently desirable to
      find more appropriate therapeutic opportunities based on informed insights. A
      molecular pharmacological analysis was undertaken to design an improved
      chemotherapeutic strategy for advanced lung cancer. METHODS: We related the
      cytotoxic activity of each of commonly used anti-cancer agents (docetaxel,
      paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and
      carboplatin (CBDCA)) to corresponding expression pattern in each of the cell
      lines using a modified NCI program. RESULTS: We performed gene expression
      analysis in lung cancer cell lines using cDNA filter and high-density
      oligonucleotide arrays. We also examined the sensitivity of these cell lines to
      these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity
      correlation data, we separately analyzed two sets of lung cancer cell lines,
      namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently
      belonged to an isolated cluster in a reproducible fashion. On the other hand,
      docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into
      one large cluster. CONCLUSION: These results suggest that chemotherapy regimens
      including gemcitabine should be evaluated in second-line chemotherapy in cases
      where the first-line chemotherapy did not include this drug. Gene expression-drug
      sensitivity correlations, as provided by the NCI program, may yield improved
      therapeutic options for treatment of specific tumor types.

PMID- 16813652
TI  - Primary adenoid cystic carcinoma of the breast: case report and review of the
      literature.
AB  - Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm accounting for
      0.1% of all breast carcinomas, and presenting most commonly as a painful breast
      mass. In contrast to the aggressive nature of ACC at other sites, ACC of the
      breast has a favorable prognosis, lymph node involvement or distant metastases
      seldom occur. Treatment is basically of simple mastectomy. Chemotherapy,
      radiation and hormonal treatment have been infrequently used and evaluated. We
      report a case of ACC of the breast managed with mastectomy and review the
      literature.

PMID- 16813651
TI  - Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and
      paclitaxel.
AB  - BACKGROUND: Tumor promoters enhance tumor yield in experimental animals without
      directly affecting the DNA of the cell. Promoters may play a role in the
      development of cancer, as humans are exposed to them in the environment. In work
      based on computer-assisted microscopy and sophisticated classification methods,
      we showed that cells could be classified by reference to a database of known
      normal and cancerous cell phenotypes. Promoters caused loss of properties
      specific to normal cells and gain of properties of cancer cells. Other compounds,
      including colchicine, had a similar effect. Colchicine given together with
      paclitaxel, however, caused cells to adopt properties of normal cells. This
      provided a rationale for tests of microtubule inhibitor combinations in cancer
      patients. The combination of a depolymerizing and a stabilizing agent is a
      superior anti-tumor treatment. The biological basis of the effect is not
      understood. RESULTS: A single compound containing both colchicine and paclitaxel
      structures was synthesized. Colchicine is an alkaloid with a trimethoxyphenyl
      ring (ring A), a ring with an acetamide linkage (ring B), and a tropolone ring
      (ring C). Although rings A and C are important for tubulin-binding activity, the
      acetamide linkage on ring B could be replaced by an amide containing a glutamate
      linker. Alteration of the C-7 site on paclitaxel similarly had little or no
      inhibitory effect on its biological activity. The linker was attached to this
      position. The coupled compound, colchitaxel (1), had some of the same effects on
      microtubules as the combination of starting compounds. It also caused shortening
      and fragmentation of the + end protein cap. CONCLUSION: Since microtubule
      inhibitor combinations give results unlike those obtained with either inhibitor
      alone, it is important to determine how such combinations affect cell shape and
      growth. Colchitaxel shows a subset of the effects of the inhibitor combination.
      Thus, it may be able to bind the relevant cellular target of the combination. It
      will be useful to determine the basis of the shape reversal effect and possibly,
      the reasons for therapeutic efficacy of microtubule inhibitor combinations.

PMID- 16813653
TI  - California Men's Health Study (CMHS): a multiethnic cohort in a managed care
      setting.
AB  - BACKGROUND: We established a male, multiethnic cohort primarily to study prostate
      cancer etiology and secondarily to study the etiologies of other cancer and non
      cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old
      males who were members of a large, prepaid health plan in California.
      Participants completed two surveys on-line or on paper in 2002-2003. Survey
      content included demographics; family, medical, and cancer screening history;
      sexuality and sexual development; lifestyle (diet, physical activity, and
      smoking); prescription and non-prescription drugs; and herbal supplements. We
      linked study data with clinical data, including laboratory, hospitalization, and
      cancer data, from electronic health plan files. We recruited 84,170 participants,
      approximately 40% from minority populations and over 5,000 who identified
      themselves as other than heterosexual. We observed a wide range of education (53%
      completed less than college) and income. PSA testing rates (75% overall) were
      highest among black participants. Body mass index (BMI) (median 27.2) was highest
      for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI
      from clinical data sources. The sensitivity and specificity can be assessed by
      comparing self-reported data, such as PSA testing, diabetes, and history of
      cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer
      diagnoses will occur within five years of cohort inception. DISCUSSION: A wide
      variety of epidemiologic, health services, and outcomes research utilizing a rich
      array of electronic, biological, and clinical resources is possible within this
      multiethnic cohort. The California Men's Health Study and other cohorts nested
      within comprehensive health delivery systems can make important contributions in
      the area of men's health.

PMID- 16813654
TI  - Hormone-replacement therapy influences gene expression profiles and is associated
      with breast-cancer prognosis: a cohort study.
AB  - BACKGROUND: Postmenopausal hormone-replacement therapy (HRT) increases breast
      cancer risk. The influence of HRT on the biology of the primary tumor, however,
      is not well understood. METHODS: We obtained breast-cancer gene expression
      profiles using Affymetrix human genome U133A arrays. We examined the relationship
      between HRT-regulated gene profiles, tumor characteristics, and recurrence-free
      survival in 72 postmenopausal women. RESULTS: HRT use in patients with estrogen
      receptor (ER) protein positive tumors (n = 72) was associated with an altered
      regulation of 276 genes. Expression profiles based on these genes clustered ER
      positive tumors into two molecular subclasses, one of which was associated with
      HRT use and had significantly better recurrence free survival despite lower ER
      levels. A comparison with external data suggested that gene regulation in tumors
      associated with HRT was negatively correlated with gene regulation induced by
      short-term estrogen exposure, but positively correlated with the effect of
      tamoxifen. CONCLUSION: Our findings suggest that post-menopausal HRT use is
      associated with a distinct gene expression profile related to better recurrence
      free survival and lower ER protein levels. Tentatively, HRT-associated gene
      expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.

PMID- 16813655
TI  - Physical activity is related to quality of life in older adults.
AB  - BACKGROUND: Physical activity is associated with health-related quality of life
      (HRQL) in clinical populations, but less is known whether this relationship
      exists in older men and women who are healthy. Thus, this study determined if
      physical activity was related to HRQL in apparently healthy, older subjects.
      METHODS: Measures were obtained from 112 male and female volunteers (70 +/- 8
      years, mean +/- SD) recruited from media advertisements and flyers around the
      Norman, Oklahoma area. Data was collected using a medical history questionnaire,
      HRQL from the Medical Outcomes Survey short form-36 questionnaire, and physical
      activity level from the Johnson Space Center physical activity scale. Subjects
      were separated into either a higher physically active group (n = 62) or a lower
      physically active group (n = 50) according to the physical activity scale.
      RESULTS: The HRQL scores in all eight domains were significantly higher (p <
      0.05) in the group reporting higher physical activity. Additionally, the more
      active group had fewer females (44% vs. 72%, p = 0.033), and lower prevalence of
      hypertension (39% vs. 60%, p = 0.041) than the low active group. After adjusting
      for gender and hypertension, the more active group had higher values in the
      following five HRQL domains: physical function (82 +/- 20 vs. 68 +/- 21, p =
      0.029), role-physical (83 +/- 34 vs. 61 +/- 36, p = 0.022), bodily pain (83 +/-
      22 vs. 66 +/- 23, p = 0.001), vitality (74 +/- 15 vs. 59 +/- 16, p = 0.001), and
      social functioning (92 +/- 18 vs. 83 +/- 19, p = 0.040). General health, role
      emotional, and mental health were not significantly different (p > 0.05) between
      the two groups. CONCLUSION: Healthy older adults who regularly participated in
      physical activity of at least moderate intensity for more than one hour per week
      had higher HRQL measures in both physical and mental domains than those who were
      less physically active. Therefore, incorporating more physical activity into the
      lifestyles of sedentary or slightly active older individuals may improve their
      HRQL.

PMID- 16813656
TI  - Contributions of differential p53 expression in the spontaneous immortalization
      of a chicken embryo fibroblast cell line.
AB  - BACKGROUND: The present study was carried out to determine whether the p53
      pathway played a role in the spontaneous immortalization of the SC-2 chicken
      embryo fibroblast (CEF) cell line that has been in continuous culture for over
      three years. RESULTS: The SC-2 cell line emerged from an extended crisis period
      with a considerably slower growth rate than primary CEF cells. The phenotype of
      the SC-2 cells changed dramatically at about passage 80, appearing smaller than
      at earlier passages (e.g., passage 43) and possessing a small, compact
      morphology. This morphological change coincided with an increase in growth rate.
      Passage 43 SC-2 cells expressed undetectable levels of p53 mRNA, but by passage
      95, the levels were elevated compared to primary passage 6 CEF cells and similar
      to levels in senescent CEF cells. However, the high level of p53 mRNA detected in
      passage 95 SC-2 cells did not correlate to functional protein activity. The
      expression levels of the p53-regulated p21WAF1 gene were significantly decreased
      in all SC-2 passages that were analyzed. Examination of the Rb pathway revealed
      that E2F-1 and p15INK4b expression fluctuated with increasing passages, with
      levels higher in passage 95 SC-2 cells compared to primary passage 6 CEF cells.
      CONCLUSION: The present study suggests that altered expression of genes involved
      in the p53 and Rb pathways, specifically, p53 and p21WAF1, may have contributed
      to the immortalization of the SC-2 CEF cell line.

PMID- 16813659
TI  - Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix.
AB  - BACKGROUND: Malignant mixed mullerian tumors (MMMT) are rare biphasic malignant
      neoplasm. The commonest site of their occurrence in female genital tract is body
      of the uterus. MMMT of the cervix is extremely rare. CASE PRESENTATION: We report
      the clinical, pathological and immunohistochemical profile and diagnostic
      difficulties in a case of giant MMMT of the cervix in a postmenopausal woman who
      presented with a large cervical mass. On microscopic examination, initially tumor
      appeared to be endometrial stromal sarcoma, however, immunohistochemical
      examination revealed the biphasic nature of the tumor. The malignant epithelial
      component was basaloid squamous carcinoma with homologous sarcomatous component.
      The patient was treated with surgery. However, she experienced vaginal vault
      recurrence four months after the initial treatment, which was successfully
      treated with pelvic radiotherapy. CONCLUSION: Accurate diagnosis of cervical MMMT
      is important for appropriate treatment of the patient.

PMID- 16813657
TI  - Spinal afferent neurons projecting to the rat lung and pleura express acid
      sensitive channels.
AB  - BACKGROUND: The acid sensitive ion channels TRPV1 (transient receptor potential
      vanilloid receptor-1) and ASIC3 (acid sensing ion channel-3) respond to tissue
      acidification in the range that occurs during painful conditions such as
      inflammation and ischemia. Here, we investigated to which extent they are
      expressed by rat dorsal root ganglion neurons projecting to lung and pleura,
      respectively. METHODS: The tracer DiI was either injected into the left lung or
      applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons
      were subjected to triple-labelling immunohistochemistry using antisera against
      TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma
      diameter was measured. RESULTS: Whereas 22% of pulmonary spinal afferents
      contained neither channel-immunoreactivity, at least one is expressed by 97% of
      pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity
      (small soma, neurofilament 68-negative) were significantly more frequent among
      pleural (35%) than pulmonary afferents (20%). TRPV1+/ASIC3+ neurons amounted to
      14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung) and 48%
      (pleura) of neurons, and half of them presumably conducted in the A-fibre range
      (larger soma, neurofilament 68-positive). CONCLUSION: Rat pleural and pulmonary
      spinal afferents express at least two different acid-sensitive channels that make
      them suitable to monitor tissue acidification. Patterns of co-expression and
      structural markers define neuronal subgroups that can be inferred to subserve
      different functions and may initiate specific reflex responses. The higher
      prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the
      high sensitivity of the parietal pleura to painful stimuli.

PMID- 16813658
TI  - A multivariate Bayesian model for assessing morbidity after coronary artery
      surgery.
AB  - INTRODUCTION: Although most risk-stratification scores are derived from
      preoperative patient variables, there are several intraoperative and
      postoperative variables that can influence prognosis. Higgins and colleagues
      previously evaluated the contribution of preoperative, intraoperative and
      postoperative predictors to the outcome. We developed a Bayes linear model to
      discriminate morbidity risk after coronary artery bypass grafting and compared it
      with three different score models: the Higgins' original scoring system, derived
      from the patient's status on admission to the intensive care unit (ICU), and two
      models designed and customized to our patient population. METHODS: We analyzed 88
      operative risk factors; 1,090 consecutive adult patients who underwent coronary
      artery bypass grafting were studied. Training and testing data sets of 740
      patients and 350 patients, respectively, were used. A stepwise approach enabled
      selection of an optimal subset of predictor variables. Model discrimination was
      assessed by receiver operating characteristic (ROC) curves, whereas calibration
      was measured using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: A set of 12
      preoperative, intraoperative and postoperative predictor variables was identified
      for the Bayes linear model. Bayes and locally customized score models fitted
      according to the Hosmer-Lemeshow test. However, the comparison between the areas
      under the ROC curve proved that the Bayes linear classifier had a significantly
      higher discrimination capacity than the score models. Calibration and
      discrimination were both much worse with Higgins' original scoring system.
      CONCLUSION: Most prediction rules use sequential numerical risk scoring to
      quantify prognosis and are an advanced form of audit. Score models are very
      attractive tools because their application in routine clinical practice is
      simple. If locally customized, they also predict patient morbidity in an
      acceptable manner. The Bayesian model seems to be a feasible alternative. It has
      better discrimination and can be tailored more easily to individual institutions.

PMID- 16813660
TI  - Validation of an English version of the Child-OIDP index, an oral health-related
      quality of life measure for children.
AB  - BACKGROUND: To evaluate the psychometric properties of the Child-OIDP for use
      among children in the UK and report on the prevalence of oral impacts in a sample
      of schoolchildren in Westminster. METHODS: Children aged 10-11 years in the final
      year of primary school (year 6) were selected from seven schools where annual
      screenings are carried out. A total of 228 children participated (99% response
      rate). A clinical examination was conducted followed by a questionnaire designed
      to measure oral health-related quality of life in children, namely the Child
      OIDP. The psychometric properties of the Child-OIDP were evaluated in terms of
      face, content and concurrent validity in addition to internal and test-retest
      reliability. RESULTS: The Child-OIDP revealed excellent validity and good
      reliability. Weighted Kappa was 0.82. Cronbach's alpha coefficient was 0.58. The
      index showed significant associations with perceived oral treatment needs and
      perceived satisfaction with mouth and oral health status (p < 0.001). CONCLUSION:
      This study has demonstrated that the Child-OIDP is a valid and reliable index to
      be used among 10-11 year old schoolchildren in the UK.

PMID- 16813661
TI  - Epidemiology and cardiovascular risk factors of aortic stenosis.
AB  - The abnormalities of aortic valve morphology and function represent the most
      common cardiac-valve lesion particularly in elderly. The etiology of aortic
      stenosis is degenerative-calcific in the majority of patients. Many risk factors
      seems to be linked to the calcification and the stenosis of the aortic valve but
      they must be confirmed. In this review the etiology and the possible
      physiopathology of the aortic valve stenosis is discussed.

PMID- 16813662
TI  - Health Related Quality of Life in Malaysian children with thalassaemia.
AB  - BACKGROUND: Health Related Quality of Life (HRQoL) studies on children with
      chronic illness such as thalassaemia are limited. We conducted the first study to
      investigate if children with thalassaemia have a lower quality of life in the
      four dimensions as measured using the PedsQL 4.0 generic Scale Score: physical,
      emotional, social and role (school) functioning compared to the healthy controls
      allowing for age, gender, ethnicity and household income. METHODS: The PedsQL 4.0
      was administered to children receiving blood transfusions and treatments at
      Hospital Kuala Lumpur, Malaysia using PedsQL 4.0 generic Scale Score.
      Accordingly, the questionnaire was also administered to a control group of
      healthy school children. Socio-demographic data were also collected from patients
      and controls using an interview schedule designed for the study. RESULTS: Of the
      96 thalassaemia patients approached, 78 gave consent to be interviewed giving a
      response rate of 81.3%. Out of 235 healthy controls approached, all agreed to
      participate giving a response rate of 100%. The mean age for the patients and
      schoolchildren is 11.9 and 13.2 years respectively. The age range for the
      patients and the schoolchildren is between 5 to 18 years and 7 to 18 years
      respectively. After controlling for age and demographic background, the
      thalassaemia patients reported having significantly lower quality of life than
      the healthy controls. CONCLUSION: Thalassaemia has a negative impact on perceived
      physical, emotional, social and school functioning in thalassaemia patients which
      was also found to be worse than the children's healthy counterparts. Continuing
      support of free desferal from the Ministry of Health should be given to these
      patients. More understanding and support especially from health authorities,
      school authorities and the society is essential to enhance their quality of life.

PMID- 16813663
TI  - Bioinformatic discovery of microRNA precursors from human ESTs and introns.
AB  - BACKGROUND: MicroRNAs (miRNAs) function in many physiological processes, and
      their discovery is beneficial for further studying their physiological functions.
      However, many of the miRNAs predicted from genomic sequences have not been
      experimentally validated to be authentic expressed RNA transcripts, thereby
      decreasing the reliability of miRNA discovery. To overcome this problem, we
      examined expressed transcripts - ESTs and intronic sequences - to identify novel
      miRNAs as well as their target genes. RESULTS: To facilitate our approach, we
      developed our scanning method using criteria based on the features of 207 known
      human pre-miRNAs to discriminate miRNAs from random sequences. We identified 208
      candidate hairpins in human ESTs and human reference gene intronic sequences, 52
      of which are known pre-miRNAs. The discovery pipeline performance was further
      assessed using 130 newly updated pre-miRNA and randomly selected sequences. We
      achieved sensitivity of 85% (110/130) and overall specificity of 49.7% using this
      method. Because miRNAs are evolutionarily conserved regulators of gene
      expression, it is expected that their host genes and target genes should have
      respective phylogenetic orthologs. Our results confirmed that, in certain
      mammals, the host genes carrying the same miRNAs are orthologs, as previously
      reported. Moreover, this observation is also the case for some of the miRNA
      target genes. CONCLUSION: We have predicted 208 human pre-miRNA candidates and
      over 10,000 putative human target genes. Using sequence information from ESTs and
      introns ensures that the predicted pre-miRNA candidates are expressed and the
      combined expression transcription information from ESTs and introns makes our
      prediction results more decisive with regard to expressed pre-miRNAs.

PMID- 16813664
TI  - Type IX collagen deficiency enhances the binding of cartilage-specific antibodies
      and arthritis severity.
AB  - Joint cartilage is attacked in both autoimmune inflammatory and osteoarthritic
      processes. Type IX collagen (CIX) is a protein of importance for cartilage
      integrity and stability. In this study we have backcrossed a transgenic
      disruption of the col9a1 gene, which leads to an absence of CIX, into two
      different inbred mouse strains, DBA/1 and B10.Q. None of the CIX-deficient mice
      developed observable clinical or microscopic osteoarthritis, but DBA/1 male mice
      had more pronounced enthesopathic arthritis, the so-called stress-induced
      arthritis. Both DBA/1 and B10.Q strains are susceptible to the induction of
      collagen-induced arthritis, and CIX deficiency in both strains led to the
      development of a more severe arthritis than in the controls. Induction of
      arthritis with monoclonal antibodies against type II collagen (CII) led to an
      earlier arthritis in the paws that also involved the knee joints. The antibodies
      used, which were specific for the J1 and the C1I epitopes of CII, initiate their
      arthritogenic attack by binding to cartilage. The C1I-specific antibodies bound
      to cartilage better in CIX-deficient mice than in wild-type animals,
      demonstrating that the lack of CIX in cartilage leads to an increased
      accessibility of structures for antibody binding and thus making the joints more
      vulnerable to inflammatory attack. These findings accentuate the importance of
      cartilage stability; cartilage disrupted as a result of genetic disorders could
      be more accessible and vulnerable to an autoimmune attack by pathogenic
      antibodies.

PMID- 16813665
TI  - Inhibitory effect of ribbon-type NF-kappaB decoy oligodeoxynucleotides on
      osteoclast induction and activity in vitro and in vivo.
AB  - In this study we examined the effect of ribbon-type (circular-type) NF-kappaB
      decoy oligodeoxynucleotides (RNODN) on osteoclast induction and activity. We
      extracted bone marrow cells from the femurs of rats and incubated non-adherent
      cells with receptor activator of nuclear factor kappaB ligand (RANKL) and
      macrophage colony-stimulating factor (M-CSF). First, transfer efficiency into
      osteoclasts and their precursors, resistance to exonuclease, and binding activity
      of decoy to NF-kappaB were examined. Next, to examine the effect of RNODN on
      osteoclast induction and activity, osteoclast differentiation and pit formation
      assays were performed. RNODN were injected into the ankle joints of rats with
      collagen-induced arthritis. Joint destruction and osteoclast activity were
      examined by histological study. The resistance of RNODN to exonuclease and their
      binding activity on NF-kappaB were both greater than those of phosphorothionated
      NF-kappaB decoy oligodeoxynucleotides. The absolute number of multinucleate cells
      scoring positive for tartrate-resistant acid phosphatase was significantly
      decreased in the RNODN-treated group. The average calcified matrix resorbed area
      was significantly decreased in the RNODN-treated group. Histological study showed
      marked suppression of joint destruction and osteoclast activity by intra
      articular injection of RNODN. These results suggest the inhibitory effect of
      RNODN on the induction and activity of osteoclasts. Direct intra-articular
      injection of RNODN into the joints may be an effective strategy for the treatment
      of arthritis.

PMID- 16813668
TI  - Applications of neuromodulation of the lower urinary tract in female urology.
AB  - Neuromodulation is becoming part of clinical armamentarium for treatment of a
      variety of lower urinary tract conditions in female urology. Its increased usage
      stems from need of patients who have exhausted all other therapeutic options for
      their complex and poorly understood lower urinary tract disorders. Currently
      neuromodulation may consist of the use of sacral nerve stimulation (SNS) and
      injectable therapies. Herein, we will discuss the background and development of
      SNS, its current indications, methods of patient selection and will review the
      results of the recent published literature on SNS. In addition, we will discuss
      some of the newer developments in SNS such as Bion device and the future
      direction in integration of SNS in female urology.

PMID- 16813666
TI  - NOS2 polymorphisms associated with the susceptibility to pulmonary arterial
      hypertension with systemic sclerosis: contribution to the transcriptional
      activity.
AB  - Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue
      fibrosis. One of several complications of SSc, pulmonary arterial hypertension
      (PAH) can be refractory to treatment, both novel and established. In the present
      study we investigated the ratio of circulating nitric oxide to endothelin-1 in
      patients with both SSc and PAH, and determined whether polymorphisms in NOS2 (the
      nitric oxide synthase 2 gene) are associated with susceptibility to PAH.
      Endothelin-1 in plasma and nitric oxide metabolites (nitrate and nitrite) in
      serum were measured. The nitric oxide/endothelin-1 ratio was significantly lower
      in patients with both SSc and PAH than in patients with SSc only or in healthy
      control individuals. We confirmed the presence of two single nucleotide
      polymorphisms at positions -1,026 and -277 and a pentanucleotide repeat (CCTTT)
      at -2.5 kilobases. There were significant differences in single nucleotide
      polymorphisms between patients with SSc who had PAH and those who did not, and
      between patients with both SSc and PAH and healthy control individuals. The CCTTT
      repeat was significantly shorter in patients with both SSc and PAH than in
      patients with SSc only or in healthy control individuals. Transcriptional
      activity were analyzed using the luciferase reporter assay. The transcriptional
      activity of NOS2 was much greater in fibroblasts transfected by a vector with a
      long allele of the CCTTT repeat than in those transfected by a vector with a
      short allele. Polymorphisms in the NOS2 gene are associated with transcriptional
      activity of the NOS2 gene and with susceptibility to SSc-related PAH.

PMID- 16813669
TI  - The effect of kidney morcellation on operative time, incision complications, and
      postoperative analgesia after laparoscopic nephrectomy.
AB  - INTRODUCTION: Compare the outcomes between kidney morcellation and two types of
      open specimen extraction incisions, several covariates need to be taken into
      consideration that have not yet been studied. MATERIALS AND METHODS: We
      retrospectively reviewed 153 consecutive patients who underwent laparoscopic
      nephrectomy at our institution, 107 who underwent specimen morcellation and 46
      with intact specimen removal, either those with connected port sites with a
      muscle-cutting incision and those with a remote, muscle-splitting incision.
      Operative time, postoperative analgesia requirements, and incisional
      complications were evaluated using univariate and multivariate analysis,
      comparing variables such as patient age, gender, body mass index (BMI),
      laterality, benign versus cancerous renal conditions, estimated blood loss,
      specimen weight, overall complications, and length of stay. RESULTS: There was no
      significant difference for operative time between the 2 treatment groups (p =
      0.65). Incision related complications occurred in 2 patients (4.4%) from the
      intact specimen group but none in the morcellation group (p = 0.03). Overall
      narcotic requirement was lower in patients with morcellated (41 mg) compared to
      intact specimen retrieval (66 mg) on univariate (p = 0.03) and multivariate
      analysis (p = 0.049). Upon further stratification, however, there was no
      significant difference in mean narcotic requirement between the morcellation and
      muscle-splitting incision subgroup (p = 0.14). CONCLUSION: Morcellation does not
      extend operative time, and is associated with significantly less postoperative
      pain compared to intact specimen retrieval overall, although this is not
      statistically significant if a remote, muscle-splitting incision is made.
      Morcellation markedly reduces the risk of incisional-related complications.

PMID- 16813670
TI  - Ultrasound guided percutaneous nephrostomy for obstructive uropathy in benign and
      malignant diseases.
AB  - OBJECTIVE: Analyze the success rate, complications and overall benefit of
      ultrasound guided percutaneous nephrostomy (PCN) for the relief of obstructive
      uropathy in benign and malignant diseases. MATERIALS AND METHODS: PCN was
      performed in 50 kidneys of 32 patients. It was performed in emergency rooms
      totally under ultrasound guidance by general surgeons. Seldinger technique was
      used in all cases. Changes in renal function after the procedure were analyzed
      using paired t-test. RESULTS: The procedure was successfully completed in 42 out
      of 50 kidneys (84%). There has been no major complication and 28% minor
      complications. The renal function improved significantly when PCN was performed
      for benign conditions (mean creatinine 3.52 mg/dL before and 2.18 mg/dL after
      PCN), however in malignancy there has been no significant improvement in renal
      function (before PCN mean creatinine 6.39 mg/dL and after PCN 5.41 mg/dL).
      CONCLUSION: We conclude that PCN can be effectively performed under ultrasound
      guidance and should be the initial procedure in acutely obstructed kidneys with
      pyonephrosis and poor renal function. In malignant cases, however, improvement in
      renal function is possible only if the procedure is carried out at an early
      stage.

PMID- 16813671
TI  - The impact of pelvicaliceal anatomical variation between the stone-bearing and
      normal contralateral kidney on stone formation in adult patients with lower
      caliceal stones.
AB  - OBJECTIVE: We aimed to investigate the effect of pelvicaliceal anatomical
      differences on the etiology of lower caliceal stones. MATERIALS AND METHODS:
      Records of adult patients between January 1996 and December 2005 with solitary
      lower caliceal stone were reviewed. After exclusion of patients with
      hydronephrosis, major renal anatomic anomalies, non-calcium stones, history of
      recurrent stone disease and previous renal surgery, 78 patients were enrolled
      into the study. Lower pole infundibulopelvic angle (IPA), infundibulovertebral
      angle (IVA), infundibular length (IL), width (IW), number of minor calices and
      cortical thickness of the lower pole together with other caliceal variables
      obtained from the whole pelvicaliceal anatomy of both stone-bearing and
      contralateral normal kidneys were measured from intravenous pyelogram of the
      patients. Total pelvicaliceal volume was also calculated by a previously
      described formula for both kidneys. RESULTS: There were statistically significant
      difference between two kidneys in terms of IW (p < 0.001) and IL (p = 0.002) of
      the upper calyx, IW (p = 0.001) and IVA (p < 0.001) of the lower calyx),
      pelvicaliceal volume (p < 0.001), IPA of middle calyx (p = 0.006) and cortical
      thickness over the lower pole (p < 0.001). However there was no difference
      between stone-bearing and contralateral normal kidneys in terms of lower pole IPA
      (p = 0.864) and IL (p = 0.568). CONCLUSION: Pelvicaliceal volume but not lower
      caliceal properties seem to be a risk factor for stone formation in lower calyx.

PMID- 16813672
TI  - Ureteroscopic pneumatic lithotripsy of impacted ureteral calculi.
AB  - INTRODUCTION: This work evaluates the results of ureteroscopic treatment of
      impacted ureteral stones with a pneumatic lithotripter. MATERIALS AND METHODS:
      From March 1997 to May 2002, 42 patients with impacted ureteral stones were
      treated by retrograde ureteroscopic pneumatic lithotripsy. Twenty-eight patients
      were female and 14 were male. The stone size ranged from 5 to 20 mm. The ureteral
      sites of the stones were distal in 21, middle in 12 and proximal in 9. RESULTS:
      Considering stones with distal location in the ureter, 1 patient had ureteral
      perforation and developed a stricture in the follow-up (4.7%). As for stones in
      the middle ureter, 2 perforations and 1 stricture were observed (8.3%) and
      regarding stones located in the proximal ureter, 5 perforations and 4 strictures
      occurred (44%). In the mid ureter, 1 ureteral avulsion was verified. In 34
      patients without ureteral perforation, only 1 developed a stricture (2.9%). Of 8
      patients who had perforation, 6 developed strictures. The overall incidence of
      stricture following treatment of impacted ureteral calculi was 14.2%.
      CONCLUSIONS: Ureteroscopy for impacted ureteral calculi is associated with a
      higher incidence of ureteral perforation and stricture. Ureteroscopy of proximal
      ureteral calculi is associated with a high risk of perforation, when compared to
      mid or distal ureteral calculi. Ureteral perforation at the site of the stone
      seems to be the primary risk factor for stricture formation in these cases.

PMID- 16813673
TI  - Complications in laparoscopic radical cystectomy. The South American experience
      with 59 cases.
AB  - OBJECTIVE: In this study, we have gathered the second largest series yet
      published on laparoscopic radical cystectomy in order to evaluate the incidence
      and cause of intra and postoperative complication, conversion to open surgery,
      and patient mortality. MATERIALS AND METHODS: From 1997 to 2005, 59 laparoscopic
      radical cystectomies were performed for the management of bladder cancer at 3
      institutions in South America. Twenty nine patients received continent urinary
      diversion, including 25 orthotopic ileal neobladders and 4 Indiana pouches. Only
      one case of continent urinary diversion was performed completely
      intracorporeally. RESULTS: Mean operative time was 337 minutes (150-600).
      Estimated intraoperative blood loss was 488 mL (50-1500) and 12 patients (20%)
      required blood transfusion. All 7 (12%) intraoperative complications were
      vascular in nature, that is, 1 epigastric vessel injury, 2 injuries to the iliac
      vessels (1 artery and 1 vein), and 4 bleedings that occurred during the bladder
      pedicles control. Eighteen (30%) postoperative complications (not counting
      mortalities) occurred, including 3 urinary tract infections, 1 pneumonia, 1 wound
      infection, 5 ileus, 2 persistent chylous drainage, 3 urinary fistulas, and 3 (5%)
      postoperative complications that required surgical intervention (2 hernias - one
      in the port site and one in the extraction incision, and 1 bowel obstruction).
      One case (1.7%) was electively converted to open surgery due to a larger tumor
      that precluded proper posterior dissection. Two mortalities (3.3%) occurred in
      this series, one early mortality due to uncontrolled upper gastrointestinal
      bleeding and one late mortality following massive pulmonary embolism.
      CONCLUSIONS: Laparoscopic radical cystectomy is a safe operation with morbidity
      and mortality rates comparable to the open surgery.

PMID- 16813674
TI  - Bilateral metastatic renal hemangiopericytoma ten years after primary
      intracranial lesion.
AB  - We report a case of bilateral metastatic renal hemangiopericytoma. A 37-year-old
      Caucasian male presented in 1993 with intracranial hemangiopericytoma. Subsequent
      metastatic disease noted years later include bilateral renal hemangiopericytoma
      10 years after initial presentation. To our knowledge, this is only the second
      reported case of bilateral metastatic renal hemangiopericytoma.

PMID- 16813675
TI  - Repeat knot formation in a patient with an indwelling ureteral stent.
AB  - A patient treated for nephrolithiasis formed knots in 2 occasions, in 2 separate
      indwelling ureteral stents. This rare complication may make stent removal
      difficult. To our knowledge, this is the first case report of repeat knot
      formation in a single patient.

PMID- 16813676
TI  - Synchronous presentation of nasopharyngeal and renal cell carcinomas.
AB  - We report a rare case of synchronous presentation of nasopharyngeal and renal
      cell carcinomas in a-50-year old male patient with long standing smoking history.
      The patient was initially presented with a diagnosis of nasopharyngeal carcinoma.
      During staging process, the abdominal computed tomography detected a right renal
      solid mass, 6.5 cm in diameter, originating from posterior portion of the right
      renal cortex. Right radical nephrectomy was performed and pathological
      examination revealed renal cell carcinoma. Smoking was thought to be a risk
      factor for both cancers. Systemic evaluation of kidney should not be discarded in
      patients diagnosed with nasopharyngeal carcinoma living in western countries with
      a smoking history.

PMID- 16813677
TI  - Brucella epididymo-orchitis: a consideration in endemic area.
AB  - Brucellosis is a zoonotic disease caused by Brucella sp. and may affect many
      parts of the body. Brucella epididymo-orchitis had been reported in up to 20% of
      patients with brucellosis. This is a case report of Brucella epididymo-orchitis
      in a Saudi male patient. He presented with a unilateral swelling of the left
      testicle. He had fever, arthralgia and night sweats. Ultrasound examination
      revealed enlarged left epididymis and testicle. Brucella serology was positive
      and the patient responded to treatment with doxycycline and gentamicin. Thus,
      brucella infection should be considered in the differential diagnosis of patients
      presenting with epididymo-orchitis from an endemic area.

PMID- 16813678
TI  - Video endoscopic inguinal lymphadenectomy (VEIL): minimally invasive resection of
      inguinal lymph nodes.
AB  - OBJECTIVES: Describe and illustrate a new minimally invasive approach for the
      radical resection of inguinal lymph nodes. SURGICAL TECHNIQUE: From the
      experience acquired in 7 operated cases, the video endoscopic inguinal
      lymphadenectomy (VEIL) technique was standardized in the following surgical
      steps: 1) Positioning of the inferior member extended in abduction, 2)
      Introduction of 3 work ports distal to the femoral triangle, 3) Expansion of the
      working space with gas, 4) Retrograde separation of the skin flap with a harmonic
      scalpel, 5) Identification and dissection of the long saphenous vein until the
      oval fossa, 6) Identification of the femoral artery, 7) Distal ligature of the
      lymph node block at the femoral triangle vertex, 8) Liberation of the lymph node
      tissue up to the great vessels above the femoral floor, 9) Distal ligature of the
      long saphenous vein, 10) Control of the saphenofemoral junction, 11) Final
      liberation of the surgical specimen and endoscopic view showing that all the
      tissue of the region was resected, 12) Removal of the surgical specimen through
      the initial orifice, 13) Vacuum drainage and synthesis of the incisions.
      COMMENTS: The VEIL technique is feasible and allows the radical removal of
      inguinal lymph nodes in the same limits of conventional surgery dissection. The
      main anatomic repairs of open surgery can be identified by the endoscopic view,
      confirming the complete removal of the lymphatic tissue within the pre
      established limits. Preliminary results suggest that this technique can
      potentially reduce surgical morbidity. Oncologic follow-up is yet premature to
      demonstrate equivalence on the oncologic point of view.

PMID- 16813679
TI  - Ballistic ureteroscopic lithotripsy in prepubertal patients: a feasible option
      for ureteral stones.
AB  - OBJECTIVE: To evaluate the role of ballistic ureteroscopic lithotripsy in
      children with ureteral stones. MATERIALS AND METHODS: Children under 14 years
      with ureteral stones were treated with ureteroscopy in a 5-year period in our
      institution. RESULTS: Twenty-three procedures were performed in 20 children. Mean
      surgical time, age and stone size were 31 min. (15 - 120 min.), 11 years. (4-13
      years), 5.3 mm (3-10 mm) respectively. Three patients underwent two ballistic
      ureteroscopic lithotripsy each. There were 22 successful procedures (96%) and a
      100% stone-free rate per patient. Complications (mucosal tear) occurred in 2
      procedures (8%) without extravasation of contrast media on retrograde pyelogram
      and their follow-up was uneventful. CONCLUSION: Ureteroscopic ballistic
      lithotripsy is a feasible option for ureteral stones in prepubertal patients,
      with high stone-free rate and few complications.

PMID- 16813680
TI  - The CAG repeat within the androgen receptor gene and its relationship to
      cryptorchidism.
AB  - PURPOSE: We examined the significance of the CAG repeat polymorphism in the
      pathogenesis of cryptorchidism. MATERIALS AND METHODS: Genomic deoxyribonucleic
      acid (DNA) was extracted from blood samples from 42 cryptorchid boys and from 31
      non-cryptorchid control subjects. In the cryptorchid group, 7 had bilateral
      cryptorchidism and 6 had patent processus vaginalis in the contralateral side. To
      determine the number of CAG repeats, the DNA was amplified by polymerase chain
      reaction and sequenced. RESULTS: The mean CAG repeat length in the AR gene was
      22.5 (range 16 to 28) in patients and 21.5 (range 17 to 26) in controls (non
      significant). Patients with bilateral cryptorchidism had a mean length of 24.3
      (range 21 to 26) and patients with unilateral cryptorchidism and patent processus
      vaginalis in the contra lateral side had a mean of 25.2 (range 21 to 28), which
      was statistically different from controls (p = 0.015 and p = 0.005 respectively).
      CONCLUSION: CAG repeat length of the AR gene does not seem to play a major role
      in patients with unilateral cryptorchidism. However, in patients with bilateral
      undescended testis, a less functional androgen receptor through a longer
      polyglutamine chain may have a role in its pathogenesis. In the same way,
      patients with unilateral cryptorchidism a contralateral patent processus
      vaginalis have longer CAG repeats that might be responsible for a slower
      testicular descent and incomplete closure of the processus vaginalis.

PMID- 16813681
TI  - Magnetic resonance imaging urodynamics. Technique development and preliminary
      results.
AB  - OBJECTIVES: In this preliminary study we report the development of the video
      urodynamic technique using magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: We studied 6 women with genuine stress urinary incontinence, diagnosed
      by history and physical examination. Urodynamic examination was performed on
      multichannel equipment with the patient in the supine position. Coughing and
      Valsalva maneuvers were performed at volumes of 150, 250 and 350 mL.
      Simultaneously, MRI was carried out by using 1.5 T GE Signa CV/i high-speed
      scanner with real time fluoroscopic imaging possibilities. Fluoroscopic imaging
      was accomplished in the corresponding planes with T2-weighted single shot fast
      spin echo sequences at a speed of about 1 frame per second. Both studies were
      recorded and synchronized, resulting in a single video urodynamic examination.
      RESULTS: Dynamic MRI with cine-loop reconstruction of 1 image per second
      demonstrated the movement of all compartment of the relaxed pelvis during
      straining with the concomitant registration of abdominal and intravesical
      pressures. In 5 patients, urinary leakage was demonstrated during straining and
      the Valsalva leak point pressure (VLPP) was determined as the vesical pressure at
      leak subtracted from baseline bladder pressure. Mean VLPP was 72.6 cm H2O
      (ranging from 43 to 122 cm H2O). CONCLUSIONS: The concept of MRI video
      urodynamics is feasible. In a clinical perspective, practical aspects represent a
      barrier to daily use and it should be recommended for research purposes.

PMID- 16813682
TI  - Defective urinary crystallization inhibition and urinary stone formation.
AB  - INTRODUCTION: Nephrocalcin (NC) is a glycoprotein produced in the kidney and
      inhibits calcium oxalate crystal formation. It has been separated into 4 isoforms
      (A, B, C, and D) and found that (A + B) are more abundant than (C + D) in urine
      of healthy subjects, but the reverse is seen in human urine of kidney stone
      patients. To further examine the role of this protein in inhibition of urinary
      crystallization, nephrocalcin isoforms were purified from 2 genetically pure dog
      species. MATERIALS AND METHODS: We studied healthy Beagles, known to be non-stone
      forming dogs, and Mini-Schnauzers, known to be calcium oxalate stone formers. NC
      was isolated and purified from each group. Urinary biochemistry and calcium
      oxalate crystal growth inhibition were measured. RESULTS: Specific crystal growth
      inhibition activity was significantly higher in non-stone forming dogs (9.79 +/-
      2.25 in Beagles vs. 2.75 +/- 1.34 of Mini-Schnauzers, p < 0.005). Dissociation
      constants toward calcium oxalate monohydrate were 10-fold different, with
      Beagles' isoforms being 10 times stronger inhibitors compare to those of Mini
      Schnauzers'. Isoforms C + D of NC were the main isoforms isolated in stone
      forming dogs. CONCLUSION: NC of these two species of dogs differently affects
      calcium oxalate crystallization and might have a role in determining ulterior
      urinary stone formation.

PMID- 16813703
TI  - Sports and the solitary kidney: how to counsel parents.
AB  - OBJECTIVE: To determine how to counsel parents of young children with a solitary
      kidney in a manner compliant with the recommendations of the American Academy of
      Pediatrics (AAP). METHODS: As per the AAP recommendations, the relevant
      information required to provide a Qualified Yes to involvement in
      contact/collision sports was obtained through a PubMed search and local
      inquiries. Questions specifically addressed were: . Available published
      information on risks of participation . Availability of effective protective
      equipment that is acceptable to the athlete . Whether the sport can be modified
      to allow safer participation. RESULTS: Pediatric renal trauma can result from
      sporting injuries, however more renal injuries are caused by motor vehicle
      accidents. Those sports associated with a higher risk of significant renal injury
      carry a five-fold higher risk of head injury. Tolerable protective equipment is
      available, but whether it decreases risk of renal trauma is unknown.
      Participation in high-risk sports can be modified to allow safer participation.
      CONCLUSIONS: Parents need to be counseled on the consequences of an injury to the
      solitary kidney, and potential ways to decrease such risks without being
      unnecessarily restrictive with respect to sports participation. Specific
      information to convey to parents in a concise manner is provided.

PMID- 16813683
TI  - Experimental supratrigonal cystectomy. Evaluation of long-term complications.
AB  - OBJECTIVE: The present study aims at assessing the occurrence of pyelonephritis
      and long-term complications in rats submitted to surgical reduction of bladder
      capacity. MATERIALS AND METHODS: Sprague-Dawley rats were submitted to
      supratrigonal cystectomy (animals) or sham operation ( animals) and sacrificed 2,
      4 and 6 months after the surgical procedure. The arterial blood pressure and
      serum creatinine levels were assessed before the surgery and at the time of the
      sacrifice. After the sacrifice a careful inspection of the urinary apparatus was
      performed to the characterization of the hydronephrosis and for the detection of
      the presence of calculi. With sterile technique, the urine was aspirated from the
      bladder and the kidneys removed and sent to a microbiologic study. RESULTS:
      Pyelonephritis was frequent in animals submitted to supratrigonal cystectomy. The
      most frequent and isolated microorganisms were Staphylococcus sp. and E. coli.
      The presence of urinary calculi was correlated significantly to the presence of
      urinary tract infection (p < 0.003). Arterial hypertension was frequent amongst
      animals submitted to supratrigonal cystectomy. Serum creatinine was high in 72.4%
      of the animals in the group submitted to supratrigonal cystectomy. The presence
      of calculi and pyelonephritis were frequent in rats presenting renal
      insufficiency and in hypertensive rats. CONCLUSIONS: The long-term course of
      urinary infection in rats submitted to supratrigonal cystectomy was characterized
      by a high incidence of renal insufficiency and arterial hypertension that seem to
      be related to dysfunction and bladder obstruction induced by an extensive
      surgical procedure and the presence of urolithiasis and pyelonephritis.

PMID- 16813704
TI  - Canadian Urological Association guidelines on urinary incontinence.
AB  - OBJECTIVE: To develop the first Canadian guidelines for the management of adult
      urinary incontinence (UI). METHOD: Following a mandate of the Canadian Urological
      Association, six Canadian urologists collaborated to produce these guidelines
      after having extensively reviewed existing foreign guidelines and literature from
      1966 to June 2005. RESULTS: The terminology proposed by the standardization
      committee of the International Continence Society (ICS) is recommended. Basic
      evaluation must include a history, physical examination, evaluation of post void
      residual volume, urinalysis and voiding diary. A more detailed evaluation is
      recommended for complex cases or if initial management fails. As non
      pharmacological treatments, devices (catheters, pessaries, etc...) play an
      important role in selected patients. Lifestyle adjustments are recommended to be
      implemented first before considering other forms of treatment. Pelvic exercises
      can be helpful for the mildest cases of pelvic relaxation, in motivated compliant
      patients. In highly selected patients neuromodulation can improve the patient's
      quality of life. Probantheline, oxybutinin and tolterodine have a proven efficacy
      in the treatment of UI. Imipramine and oestrogens are suggested while flavoxate
      has an unproven efficacy. Surgery in women is indicated when the degree of
      incontinence is sufficiently troublesome to the patient, the incontinence has
      been observed by the examiner, its causes adequately evaluated and conservative
      therapies have been reviewed. Primary stress urinary incontinence in the female
      is effectively treated by a retropubic suspension (Burch or Marshall- Marchetti
      Krantz), or a pubovaginal sling procedure. Pubovaginal slings are the procedure
      of choice in the presence of significant intrinsic sphincteric deficiency (ISD),
      the absence of hypermobility, or in the treatment following a failed retropubic
      suspension. Peri urethral injectables are recommended first line treatment of SUI
      when available. In men, artificial sphincter is the treatment of choice in
      neurogenic and non-neurogenic SUI. In neurogenic bladders and sometimes in non
      neurogenic bladders other forms of surgeries such as bladder denervation, bladder
      augmentations, neurostimulation, urinary diversion can be considered as the
      treatment of choice for individual patients. CONCLUSION: Canadian guidelines on
      incontinence have been completed in 2005 reflecting the Canadian health
      environment. This field of UI is in constant progression and, when of proven
      efficacy, new medications and devices have to be included in the proposed
      algorithm of care.

PMID- 16813706
TI  - Status of urologic laparoscopy in 2004: a survey of CUA members.
AB  - INTRODUCTION: The optimal method of acquiring laparoscopic skills has not been
      determined. We sought to examine the current status of urologic laparoscopy and
      how practicing urologists acquired the skills needed to perform laparoscopic
      procedures. METHODS: A mail questionnaire regarding laparoscopic practices and
      training was sent to 480 members of the Canadian Urological Association (CUA)
      using standard Dillman survey methodology. RESULTS: Three hundred (62.5%)
      urologists responded to the questionnaire; 56.5% practiced in the community and
      41.1% in an academic setting. There were 59.9% who had completed some form of
      fellowship training. Recent graduates (who finished residency after 1995) were
      more likely to perform all types of laparoscopic procedures compared to older
      graduates (65% versus 29.7%, p < 0.001). Advanced procedures were also performed
      more frequently by recent graduates (52.5% versus 23.4%, p < 0.001). Of those who
      do not currently perform laparoscopy, 38.2% plan to learn in the future. The most
      common method of acquiring laparoscopic skills was with animal laboratory
      experience (39.4%), but only 20.9% relied solely on this method. A trip to a
      centre of excellence (28.5%) and training from an urologist at the same
      institution (25.7 %) was also commonly reported as methods of acquiring skills.
      There were 48.8% who reported beginning laparoscopic procedures without a mentor.
      CONCLUSIONS: A substantial portion of the Canadian urological community employs
      laparoscopy, although recent graduates are more likely to do so. Training methods
      in laparoscopy are variable, but a substantial portion of urologists begin
      practicing laparoscopic procedures without formal mentoring.

PMID- 16813705
TI  - Prospective evaluation of the prevalence and severity of fatigue in patients with
      prostate cancer undergoing radical external beam radiotherapy and neoadjuvant
      hormone therapy.
AB  - OBJECTIVE: To prospectively evaluate the prevalence and severity of fatigue and
      its impact on quality of life (QOL) during and after radical external beam
      radiotherapy (RT) for prostate cancer. METHOD AND MATERIALS: Twenty-eight men
      with prostate cancer undergoing RT over 6-8 consecutive weeks were prospectively
      accrued. The Brief Fatigue Inventory (BFI), a validated fatigue assessment tool,
      was administered at five time points: baseline (week 1), middle of RT (week 3-4),
      end of RT (last week of RT), and follow-up (median 6.5 weeks after RT). The BFI
      contained nine questions, each using 0-10 ratings to quantify fatigue severity
      and interference with six QOL domains. The prevalence of moderate-severe fatigue
      was plotted as a function of time. Mean sum and subscale scores at each time
      point were compared to baseline scores using Wilcoxon tests. Linear regression
      analyses were performed to assess associations between fatigue scores and age,
      tumor and treatment characteristics. RESULTS: The median age was 69 years (range
      57-84), Gleason score 7 (range 6-10), and presenting PSA 9.0 ng/mL (range 2.5
      ng/mL-103.0 ng/mL). Patients were treated once daily to a median dose of 74 Gy
      (range 60 Gy-78 Gy) over a median of 37 fractions (range 30-39). Hormone therapy
      was used in all patients (median duration 12.2 months). The prevalence of
      moderate-severe present fatigue increased from 7% at baseline to 8% at mid-RT and
      32% at RT completion. Compared to baseline (mean score 11.5), fatigue increased
      significantly mid-RT (mean score 14.6, p = 0.03) and peaked at the end of RT
      (mean score 23.5, p = 0.001). Fatigue significantly interfered with walking
      ability, normal work, daily chores, and enjoyment of life only at the end of RT.
      After RT completion, fatigue improved but remained higher compared to baseline at
      6.5 weeks of follow-up (mean score 15.0, p = 0.02). On linear regression
      analysis, age, Gleason score, PSA, T-stage, hormone therapy duration, RT dose and
      fractions were not significantly associated with mean fatigue scores. CONCLUSION:
      Patients undergoing 6-8 weeks of RT experienced significant fatigue adversely
      affecting QOL persisting after therapy completion. Since walking ability was not
      affected until the end of RT, a walking exercise intervention to combat fatigue
      is likely feasible and is being investigated.

PMID- 16813707
TI  - Percutaneous nephrolithotomy under conscious sedation in morbidly obese patients.
AB  - Two morbidly obese males weighing 159 kg and 184 kg underwent percutaneous
      nephrolithotomy (PCNL) for large, symptomatic renal stones. To avoid anesthetic
      complications and cardiorespiratory compromise in the prone position, the
      procedures were performed under IV sedation with local anesthesia. The risks of
      PCNL in this patient population are reviewed, and the technique employed to
      mitigate the risks in these two cases is described.

PMID- 16813708
TI  - Retrograde stenting of transplant ureters using a ureteral access sheath.
AB  - Changing chronic ureteral stents in patients with kidney transplants may be
      technically difficult because of the site of ureterocystostomy. The technique
      described simplifies this procedure.

PMID- 16813709
TI  - Parameters affecting urologic complications after major joint replacement
      surgery.
AB  - INTRODUCTION AND OBJECTIVES: Peri-operative bladder management after major
      arthroplasty procedures remains controversial. The purpose of this study was to
      assess the risk of urological complications in those patients undergoing hip or
      knee joint replacement. As well, we identified those factors that may affect the
      likelihood of developing complications. METHODS: Two hundred and twenty-one
      consecutive patients receiving a total knee or hip arthroplasty were reviewed.
      The outcomes measured were prolonged urinary retention, as well as urinary tract
      infections and the development of a septic prosthesis. Statistical significance
      of any predisposing factors identified was determined using a two-tailed Fisher
      exact test. RESULTS: Urological complications in the cohort were common at 47%,
      with patients having hip arthroplasty being at higher risk (p < 0.03). Despite
      this there was a low incidence of documented infections. Increased rates of
      urinary retention were identified in those who received intrathecal narcotics (p
      < 0.02), as well as those who suffered from hypertension (p < 0.05). Gender and
      anesthetic techniques (general or regional) did not affect the rate of
      complications. There was a decrease in urological complications when bladder
      management included peri-operative catheterization rather than expectant
      management. CONCLUSIONS: Bladder management is a significant problem for patients
      after hip and knee arthroplasty as urinary retention was identified in almost
      half of the patients. Parameters that may identify those with higher risks
      include patients with hypertension and those who receive intrathecal narcotics.
      In high-risk patients, the practice of utilizing a catheter peri-operatively may
      decrease the risk of multiple post-operative catheterizations without increasing
      the rate of infections.

PMID- 16813710
TI  - Resident involvement in open radical prostatectomy: a review of urology surgical
      training.
AB  - PURPOSE: The Royal College of Physicians and Surgeons of Canada (RCPSC) and The
      American Accreditation Council for Graduate Medical Education (ACGME) general
      objectives mandate that all residents be competent to independently perform
      select surgical procedures. Unfortunately, no objective standardized measures
      presently exist for surgical training assessment. Operative logs have been
      implemented to quantify the number of cases the resident has been exposed to,
      however, these do not assess their degree of involvement or aptitude. An analysis
      of what exactly a resident performs, and how well, per case may assist in
      measuring their training progress. Herein, we evaluate a questionnaire to
      quantify the level of resident participation in radical retropubic prostatectomy
      (RRP) and assess whether resident perception of how much involvement in a case
      correlates with staff surgeons. METHODS AND MATERIALS: Identical, self
      administered questionnaires were distributed simultaneously to the resident and
      staff urologist upon completion of radical prostatectomy. The questionnaire
      comprised of 14 items, which were completed independently by the resident and the
      staff urologist. The items assessed which of the 14 specific surgical steps were
      actually performed by the resident. An analysis was performed to assess the level
      of agreement. RESULTS: Among all cases performed between June 2002 and July 2003,
      64 RRPs performed by two surgeons had completed questionnaires by both resident
      and staff. Twenty-one (32.8%) cases were performed with a senior resident (R4)
      and 43 (67.2%) cases were performed with a chief resident (R5). Twenty (31.3%)
      cases involved pelvic lymph node dissection. Resident performance of key surgical
      steps, namely dorsal venous ligation, urethral division, lateral pedicle
      dissection and urethrovesical anastamosis was 59.4%, 62.5%, 84% and 59.4%
      respectively. Global level of agreement between staff and resident responses was
      94.9% (71.4%-100%). CONCLUSION: Our results suggest that there exists good
      agreement between resident perception of their level of involvement in RRP and
      staff validation. As such, a residents' assessment of their participation is
      likely to be accurate. Designation of performance of key operative steps into
      logs may be more relevant than recording simple exposure to index cases. Attempts
      at measuring quality of key operative steps in the future may be beneficial.

PMID- 16813711
TI  - [Cytofluorometric analysis of chosen markers of apoptosis CD95/CD95L (Fas/FasL)
      in thyroid tissues from young patients with Graves' disease and Hashimoto's
      thyroiditis].
AB  - BACKGROUND: Apoptosis, one of the forms of programmed cell death, is a
      physiologic process of cell death that is central to normal development and
      occurs in response to a variety of physiologic and pathophysiologic stimuli. In
      the thyroid, abnormal apoptotic activity may be involved in a variety of diseases
      such as Hashimoto thyroiditis and Graves disease. The aim of this study was to
      estimate the expression of chosen apoptotic molecules CD95 (Fas) and CD95L (FasL)
      on the surface of thyroid follicular cells in application of mouse monoclonal
      antibodies #64 which recognized B antigen regions of thyroid peroxidase (TPO) and
      infiltrating inflammatory cells. MATERIAL AND METHODS: The investigation was
      performed on thyroid cells isolated from surgically treated thyroid tissues of 15
      patients with Graves' disease (GD), 15 patients with a nontoxic multinodular
      goiter (NTMG) and 15 aspirates obtained by FNAB from patients with Hashimoto
      thyroiditis (HT). The thyrocytes were identified by an indirect method: in the
      first stage we added mouse monoclonal autoantibodies specific for TPO (mAb #64)
      regions and in the second stage we conjugated this complex with rabbit anti-mouse
      antibodies IgG (Fab')2 with FITC. In the next step the cellular suspension was
      completed with suitably well-chosen two-colour monoclonal antibodies marked (PE
      or PerCP) (Becton Dickinson) directed against suitable apoptotic (Fas/FasL)
      molecules. All investigations were performed by flow cytometry using Coulter
      EPICS XL apparatus. RESULTS: The percentages of thyroid cells were estimated with
      expression of region B antigenic TPO in reference to individual apoptotic
      molecules. The analysis of Fas and FasL expression in thyroid tissues revealed
      significantly increased percentage of intrathyroidal T cells with CD95+ (p<0.005,
      p<0.001), CD95L+ (p<0.02, p<0.01) and both CD95/CD95L (ns, p<0.05) expression in
      comparison to percentages of T cells in patients with HT and NTMG. In addition,
      on the surface of thyroid follicular cells in patients with GD (p<0.01, p<0.01)
      and NTMG (p<0.001, p<0.004) we observed a lower percentage of thyrocytes with
      CD95 and CD95L molecules than in cases with HT. The expression of both apoptotic
      molecules on thyroid cells was higher (18%) in patients with HT in comparison to
      the percentages of positive cells in patients with GD (p<0.02, p<0.002) and NTMG,
      8% and 1%, respectively. CONCLUSIONS: We conclude that alterations in the
      expression of death receptors and their ligands on the surface of thyroid
      follicular cells may play a role in the regulation of apoptosis in thyroid
      autoimmune disorders.

PMID- 16813712
TI  - [Relationship between body mass index and leptin levels in children treated for
      acute lymphoblastic leukemia during and after maintenance therapy].
AB  - We analyzed the relationship between serum leptin levels and body mass index in
      children treated for acute lymphoblastic leukemia during and after the
      maintenance therapy. MATERIAL AND METHODS: We studied 99 survivors (62 boys) in
      mean age 12.65 years +/- who have been treated for ALL according to the Polish
      Paediatric Leukemia and Lymphoma Study Group. During the maintenance therapy
      there were n=34 patients (23 boys) and after treatment n=75 (39 boys). 16
      patients received cranial irradiation (12 Gy). We calculated body mass index
      (BMI) using the formula weight/(height)2 (kg/m2). Leptin levels were measured
      with the RIA method. The results were expressed as SDS. RESULTS: 1. No difference
      was found in leptin SDS and BMI SDS from zero -- in the whole study group,
      similar in boys and girls. The leptin/BMI ratio was significantly higher in girls
      than in boys. 2. No differences were observed in the group during and after
      therapy in values of BMI SDS and leptin SDS. We found higher leptin SDS in boys
      during (4.86+/-1.01) and after puberty (1.53+/-0.75). We found higher leptin SDS
      in boys than in girls during (1.6+/-1.1 vs. 0.6+/-0.6) and after therapy. 3. In
      boys and girls diagnosed before puberty leptin SDS were higher in boys (1.7+/-1.3
      vs. 0.2+/-1.7). The leptin/BMI ratio was significantly higher in girls than in
      boys diagnosed before puberty. 4. We found correlations between leptin levels and
      BMI in the whole group as well as in boys and girls analysed according to puberty
      and time of treatment. 5. No differences were observed between patients with and
      without cranial irradiation. CONCLUSIONS: Anti-neoplastic treatment for acute
      lymphoblastic leukemia and age of disease did not influence body mass index and
      leptin level in the examined population.

PMID- 16813713
TI  - [Correlation analysis between diabetic retinopathy and early atherosclerotic
      changes in adolescents with type 1 diabetes -- preliminary report].
AB  - OBJECTIVE: Recent studies have shown a correlation between advanced diabetic
      retinopathy and late stages of atherosclerosis. There are no findings on a
      possible relation between diabetic retinopathy and diseases of the cardiovascular
      system at their earliest stage in young people with diabetes type 1. The purpose
      of the study was to analyze a correlation between diabetic retinopathy and early
      atherosclerotic changes in adolescents with type 1 diabetes. RESEARCH DESIGN AND
      METHODS: The study included 28 adolescents aged 17.6+/-1.4 years suffering from
      type 1 diabetes mellitus for 7.9+/-3.1 years, the mean age of the disease onset -
      9.5+/-3.7 years, a mean level of HbA1c - 8.6+/-1.9%. Eight patients with
      developing simple retinopathy, were separated from the whole group of young
      people. First control group consisted of the remaining patients with type 1
      diabetes chosen with regard to age and sex, without disease complications. Second
      control group consisted of 11 healthy young people. The function of endothelium
      by measuring the brachial artery dilatation -- FMD and the intima-media complex
      thickness of the common carotid arteries were evaluated ultrasonographically.
      RESULTS: Young people with retinopathy had higher systolic pressure: 133+/-19
      mmHg in comparison with patients without complications: 117+/-14 mmHg (p<0.05)
      and healthy people: 115+/-8 mmHg (p<0.05). All patients with diabetes showed
      significantly lower FMD (7.6+/-5.1%, p<0.05). In the group with retinopathy, FMD
      equaled 7.8+/-4.1% (p=0.04) and in the group without retinopathy - 7.6+/-5.5%
      (p<0.05) in comparison with 12.1+/-5.1% in healthy volunteers. Significantly
      higher IMT was found in all patients with diabetes in comparison with healthy
      young people: 0.49+/-0.06 vs. 0.42+/-0.03 mm (p<0.001). Patients with retinopathy
      had a significantly higher value of IMT in comparison not only with controls but
      also with patients without complications: 0.56+/-0.06 vs. 0.47+/-0.03 mm
      (p<0.001). CONCLUSIONS: 1. Young people with type 1 diabetes had a significantly
      impaired function of endothelium and higher IMT in comparison with healthy young
      people. 2. Adolescents with retinopathy were characterized by significantly
      higher values of systolic arterial blood pressure when compared to patients
      without complications 3. Higher IMT was found in patients with diabetic
      retinopathy in comparison with patients without complications, which may suggest
      that macrovascular changes are more advanced in case of complications than in
      patients without retinopathy.

PMID- 16813714
TI  - [The assessment of 24-hour ambulatory blood pressure monitoring (ABPM),
      microalbuminuria and diabetic autonomous neuropathy in children with type 1
      diabetes and hypertension].
AB  - INTRODUCTION: The late complications of diabetes consisted of autonomic
      neuropathy, nephropathy, which more often coexist with hypertension in children
      with type 1 diabetes mellitus. THE AIM OF THE STUDY was to assess the connections
      between changes in the autonomous nervous system, 24-hour ABPM and daily albumin
      excrection in children with hypertension and type 1 diabetes mellitus. MATERIAL:
      The group consisted of 72 patients with diabetes (diabetes duration time 6.5+/
      1.5 years). 34 patients of that group have hypertension. The control group
      consisted of 30 healthy children matched according to age and sex. RESULTS: In
      children with hypertension we found significantly often occurrence of
      microalbuminuria (13/34 i 1/38, p<0.001). In 17 patients from the group with
      hypertension and 17 patients without hypertension we affirm signs of autonomic
      neuropathy. The values of heart rate variability (HRV) were significantly
      decreased in the group with hypertension as compared to the control group. A
      stepwise multiple regression analysis with hypertension as a dependent variable
      and diabetes duration time, microalbuminuria, HbA1c level, HRV parameters and a
      presence of autonomous neuropathy as predictors proved that hypertension is
      associated with higher HbA1c level (b=0.35), the presence of autonomous
      neuropathy (b=0.28), and lower HF values (b=0.41) (p<0.01). CONCLUSIONS:
      Hypertension in children with type 1 diabetes mellitus is correlated with the
      presence of autonomous neuropathy, higher HbA1c level and lowered values of heart
      rate variability parameters.

PMID- 16813715
TI  - [Insulin resistance in type 1 diabetic children and adolescents -- a simplified
      method of estimation].
AB  - BACKGROUND AND AIM OF THE STUDY: Our own studies confirm the hypothesis, that
      insulin resistance of various degree is often observed in children and
      adolescents with type 1 diabetes mellitus (T1DM). The knowledge of this parameter
      characterizing individual patients may be of great value not only for better
      understanding of the disease course but also as a potential source of specific
      treatment. Reliable estimation of insulin resistance with hyperinsulinemic
      euglycemic clamp is a complex, laborious and costly procedure. These facts were
      enough to motivate us to make an attempt to elaborate an indirect, simplified
      method of insulin resistance assessment in T1DM children, that would be based on
      patients characteristics and on clinical parameters of the disease course.
      MATERIALS AND METHODS: 142 children and adolescents with T1DM (79 boys, 63 girls)
      aged 7.7-20.3 years (mean age - 13.7+/-3.3 years) were included into the study.
      Duration of diabetes was 0.5-12.5 years (mean 2.7+/-2.3 years). The stage of
      puberty was assessed by the Tanner scale. Euglycemic-hyperinsulinemic clamp by de
      Fronzo was performed to estimate insulin resistance. Glucose disposal rate (M
      index) determined during the last 30 min of the test estimated insulin
      resistance. Looking for clinical and metabolic factors characterizing insulin
      resistance: a) the plasma cholesterol, HDL-Ch, triglycerides and HbA1c were
      examined, b) the height, weight, waist circumference and blood pressure were
      measured, c) body mass index and daily dose of insulin were calculated. For
      statistical analysis the multiple regression was used (forward stepwise method).
      RESULTS: In the study group M index ranged from 2.1 to 17.4 mg/kg/min (mean
      7.27+/-2.62 mg/kg/min). The boys presented better insulin sensitivity than girls
      (7.79 vs. 6.62, p=0.008). The insulin resistance depended on the patients' age
      (r=-0.46, p<0.001) and stage of puberty (p<0.001). A correlation between M index
      and insulin dose (r=-0.34, p<0.05) and HbA1c (r=-0.17; p=0.04) were found. There
      was a significant relationship between M index and parameters of adiposity,
      lipids and blood pressure. All significant clinical parameters of insulin
      resistance were subjected to the analysis. Multiple linear regression analysis
      was performed. The model with the strongest correlation with index M was used to
      work out the formula: M index = 17.065 + 1.547 x (gender: boys=1, girls=0) -
      0,183 x (age) - 0,117 x (Waist circumference) - 2,019 x (Daily insulin dose) -
      0,016 x (LDL-CH) + 0,041 x (DBP). CONCLUSION: In T1DM children and adolescents it
      is possible to estimate for daily use extent of insulin resistance on the basis
      of clinical features.

PMID- 16813716
TI  - [Assessment of the dietary habits of short girls and boys].
AB  - BACKGROUND: The problem of body height deficiency, being the effect of
      undernutrition of children in developing countries, is widely described in the
      literature, whereas very little attention is devoted to the estimation of the
      nourishment of children and adolescents with a simple body height deficiency in
      developed countries. AIM OF THE STUDY: The purpose of the study was to estimate
      the nourishment of short-height girls and boys, with special regard to the
      realisation of the norms of daily demand for basic nutrients. MATERIAL AND
      METHODS: The investigation included 60 subjects in two age groups: 10.5 and 13.5
      years old. The body height of the investigated children was below 10 centile in
      relation to the development norms for a given age and gender. Estimations of
      nourishment were made with the use of an interview about the consumption in the
      last 24 hours. RESULTS: In 22% of the investigated, energy intake was found to be
      lower than 75% of the daily demand. The percentage of the realisation of the norm
      for mineral components amounted on average to: 38.6-56.7% for calcium; 49.2-77.4%
      for iron; 50.1-93.2% and 45.9-72.2% for zinc and copper, respectively.
      Hypovitaminosis was relatively much less marked in comparison with the deficiency
      of mineral components. A lower consumption of animal protein and vitamin C was
      noted among adolescents from rural areas. CONCLUSION: Among short girls and boys
      a frequent occurrence of deficiency of energy and mineral components (calcium,
      zinc, copper and iron) was found. The irregularly balanced diet could be the
      cause of a smaller body height in relation to peers among a considerable
      percentage of the investigated adolescents.

PMID- 16813717
TI  - [Declared attitudes of girls with Turner's syndrome towards physical education
      classes].
AB  - OBJECTIVES: To learn the attitudes and opinions of girls with Turner's syndrome
      about physical education classes and to determine the level of physical activity
      of those girls by applying the MVPA (moderate-to-vigorous physical activity)
      index. MATERIAL AND METHODS: A group of 36 girls with Turner's syndrome, aged 10
      19 years, participants of a summer camp at the sea shore in 2004, were subjected
      to a questionnaire study. The resulting MVPA index served as an indicator of the
      degree of physical activity. RESULTS: About one-fourth of girls were chronically
      disqualified by physicians from physical education (PE) classes, 69% declared
      they "liked" or "liked very much" PE classes, but only 29% stated that the degree
      of difficulty of PE activities matched the abilities of schoolchildren. Mean MVPA
      value in those girls amounted to 3.5 days a week and only 19% of girls met the
      recommended level of 5 or more days a week. SUMMARY AND CONCLUSIONS: The girls
      with Turner's syndrome had good opinions of their PE teachers but the
      participation of those girls in physical activities was unsatisfactory. The
      teachers ought to seek efficient ways to motivate schoolchildren for increasing
      their physical activities and their participation in various forms of sport and
      leisure activities.

PMID- 16813718
TI  - [Physical fitness of short-statured boys as related to percentile norms for
      calendar or growth age].
AB  - OBJECTIVES: To assess the physical fitness of short-statured boys aged 7 - 20
      years by applying fitness norms established for the Polish population in relation
      to calendar or growth age. MATERIAL AND METHODS: The results of EUROFIT fitness
      tests recorded in 3517 short-statured (below percentile 10 for body height) boys,
      aged 7-20 years, selected from a large (n=37 000) representative male cohort,
      were analysed. RESULTS: Individual results were confronted with the respective
      percentile norms related to calendar age (CA) or growth age (GA), since body
      height deficiency at given CA could have affected the results of fitness tests
      expected for that CA. The percentages of subjects below, the percentile 3 or
      above percentile 97 for given fitness test and CA or GA for the Polish
      population, were determined. No differences between the percentages computed for
      CA and GA were noted in case of the following tests: sit-and-reach (SAR) and bent
      arm hang (BAH). Significant differences in percentages for both percentiles were
      found for the following tests: standing broad jump (SBJ), endurance shuttle run
      (ESR), handgrip (HGR) and plate tapping (PLT). In case of sit-ups (SUP)
      significant differences in percentages between CA and GA norms were found below
      the percentile 3, and in case of shuttle run (SHR) and flamingo balance (FLB) --
      above percentile 97. SUMMARY AND CONCLUSIONS: Fitness tests were classified into
      two categories according to the differences between the results related to norms
      for calendar or growth age: those independent of whether CA or GA norms were
      applied (SAR and BAH), and those susceptible to the kind of norm (SBJ, HGR, PLT,
      SHR, FLB and SUP). The results of tests from the latter category should thus be
      evaluated by confronting them with the norms established for the growth age, and
      not calendar age.

PMID- 16813720
TI  - [Sense of self-contact experienced by an obese child].
AB  - BACKGROUND: Sense of self-contact experienced by a child is a mental availability
      of the contents of self-experience. It is a possibility of identifying and
      expressing the contents of own feelings, experiences and conditions. Sense of
      self-contact is an element of a sense of identity. The sense of identity involves
      the contents of mental self-experiencing, sense of differentiation and sense of
      continuity. OBJECTIVES: The aim of this article is an attempt to answer what is a
      sense of self-contact experienced by an obese child. MATERIAL AND METHODS: 142
      children have been examined (71 obese and 71 slim) at the age from 5 to 10 years.
      Children Apperception Test, the version with animal figures (CAT-A) has been used
      to children examination. The CAT-A consists of 10 black-white pictures presenting
      animals in different situations, significant in view of the child's development
      and functioning. RESULTS: The specific difficulties in an experience of self
      contact by an obese child were pointed out. CONCLUSION: Psychotherapy should be
      aimed at finding internal, mental points for self-description, thus also the
      sense of mental self-contact and self experience in personal dimension.

PMID- 16813719
TI  - [Turner's syndrome: subjects with a normal body mass at birth grow taller than
      born small for gestational age].
AB  - BACKGROUND: Body mass deficit at birth is one of the characteristic features
      observed in Turner's syndrome (TS). Body mass is lower than expected for
      gestational age in about 90% of TS-babies, and is below -2 SD (i.e. "small for
      gestational age") in about 20% of patients. OBJECTIVES: The aim of the study was
      to compare the growth courses of TS-girls born with normal and deficient body
      mass. PATIENTS: A group of 157 TS-girls, delivered at term (> or =38 weeks of
      gestation), were studied. Body mass of 80 girls ranged from -0.5 to +0.5 SD and
      body length was above -2 SD (AGA group); another 54 girls had body mass below -2
      SD and body length above -2 SD (disproportional SGA group), and 23 girls had both
      body mass and length below -2 SD (proportional SGA group). METHODS: Turner's
      syndrome was confirmed by chromosome analysis. Body mass at birth (BMB) was
      related to the norms for gestational age (GA) designed by Usher and McLean.
      Newborns, whose BMB was lower than -2 SD for GA, were considered small for
      gestational age (SGA). Postnatal body height and mass values were related to
      Polish norms for females with Turner's syndrome and to the norms for healthy
      female population. RESULTS: In the spontaneously growing TS-girls from the AGA
      group, a total of 275 measurements of body mass and height were carried out, the
      respective numbers for DSGA and PSGA groups were 176 and 100. Mean differences
      between the actual and expected body height for the AGA, DSGA and PSGA groups
      amounted to 0.40+/- 1.02, -0.21+/-0.88 and -0.95+/-0.80 SD TS, respectively, all
      means differing highly significantly (p<0.001) from each other. CONCLUSION: It
      may be concluded that spontaneously growing girls with Turner's syndrome, who had
      a normal (for gestational age) body mass at birth, attain a higher stature than
      girls with body mass deficit.

PMID- 16813721
TI  - [Effect of growth hormone therapy in a 14-years-old boy with Crohn's disease and
      growth hormone deficiency].
AB  - We present a case of a 14-year-old boy in whom, at age of nine a dramatic
      decrease of growth velocity was observed. At the age of 14 the growth hormone
      therapy was introduced after the diagnosis of partial growth hormone deficiency
      and Crohn's disease. During the two years period of follow up increased growth
      velocity and improvement in the general condition was observed. We present the
      case because of many controversial opinions about growth hormone treatment in
      Crohn's disease.

PMID- 16813722
TI  - [Incidentaloma in a 16 years old girl -- 2 year observation].
AB  - Adenomas of the hypophysis are tumors of the CNS which are on the third place in
      the frequency of appearance, which cause disturbances of hypophyseal function. In
      children incidentaloma is seldom observed. The authors present a 16-year-old girl
      who was admitted to the clinic because of amenorrhoea and an increased growth
      velocity during the last year. The MRI examination of the hypophysis proved a
      hypophyseal adenoma. Hormonal laboratory examinations do not show any hormonal
      activity of the observation. The girl's case is presented because the diagnosis
      of an incidentaloma is exceptionally rare in this age group.

PMID- 16813723
TI  - Employee attitudes and smoking behavior at the City of Hope National Medical
      Center smoke-free campus.
AB  - Since 1989, City of Hope National Medical Center (COH), located in Duarte,
      California, and a member of the National Comprehensive Cancer Network, has
      prohibited smoking anywhere on the 100-acre campus. Because little published
      information is available on smoke-free campuses (SFCs), we investigated the
      attitudes of COH employees toward the SFC and attempted to answer the question of
      whether a difference in employee smoking behavior occurred and was attributable
      to the SFC policy. An anonymous survey was sent to all 2787 campus employees
      using both Web-based data entry and scannable paper forms. Employees with network
      access were contacted by e-mail and those without computers were contacted in
      person. Respondents were asked questions regarding their attitudes toward the SFC
      and about their smoking history and current smoking behavior. A total of 1356
      responses (48.7%) were received. One hundred (7.4%) respondents were current
      smokers, 242 (17.8%) were ex-smokers, and 1014 (74.8%) were nonsmokers. Smokers
      and ex-smokers smoked a mean of 2.4 fewer cigarettes (95% CI, 1.8 to 3.1; P <
      .0001) on workdays than on days off, with evidence of a small amount of
      compensatory smoking (one cigarette per day). Of the smoking employees, 61.6%
      believed that the SFC reduced their cigarette consumption, and 42.2% quit smoking
      while employed at COH between 1989 and 2002. Of all respondents, 92.6% supported
      the COH SFC policy. High acceptance was consistent across gender, ethnicity, job
      type, and educational level. COH's SFC policy is strongly supported by employees
      and may decrease cigarette consumption and facilitate smoking cessation among
      smoking employees. This information may be useful to NCCN and other medical
      centers in assessing current and planning future campus smoking policies.

PMID- 16813724
TI  - Non-small cell lung cancer clinical practice guidelines in oncology.

PMID- 16813725
TI  - A brief review of pharmacotherapies for smoking cessation.
AB  - The U.S. Department of Health and Human Services' Clinical Practice Guidelines
      have established both nicotine and nonnicotine-based pharmacotherapies as
      efficacious treatments for smoking cessation. Smokers attempting to quit smoking
      can significantly increase their chances by using one of several first-line
      agents, including nicotine transdermal patches, gum, nasal spray, inhalers,
      tablets, and the antidepressant bupropion. Those who cannot use either bupropion
      or nicotine replacement therapy because of contraindications or lack of
      effectiveness may benefit from the second-line treatment nortriptyline. This
      article also discusses several novel compounds for smoking cessation.

PMID- 16813726
TI  - Computed tomography screening for the early detection of lung cancer.
AB  - Although lung cancer is the leading cause of cancer-related death in the world
      and has an increased chance of cure if detected at an earlier stage, routine lung
      cancer screening is currently not recommended in the United States.
      Unfortunately, most patients with lung cancer present only after the onset of
      symptoms and have advanced disease that cannot be surgically resected. The
      overall 5-year survival rate for all patients with lung cancer is only 15%. When
      the cancer is detected at its earliest stage (pathologic stage IA), however, the
      5-year survival rate is more than 70%. Although past randomized screening trials
      evaluating the use of standard chest radiography or sputum cytology have not
      resulted in lower mortality, recent studies suggest that computed tomography (CT)
      may have promise as a screening tool. This article summarizes experience over the
      past decade of using low-dose spiral CT imaging as a screening tool to detect
      early lung cancers in asymptomatic, high-risk individuals.

PMID- 16813727
TI  - Adjuvant treatment in non-small cell lung cancer: Where are we now?
AB  - Lung cancer is the most common cancer worldwide, accounting for 1.2 million new
      cases annually. Despite aggressive local management of patients diagnosed with
      early-stage disease (stages I-IIIA), more than half of patients who have
      undergone surgical resection will die from complications caused by recurrent lung
      cancer. Over the past 5 years, results from several large trials assessing the
      use of adjuvant platinum-based chemotherapy in non-small cell lung cancer have
      become available. This article reviews the data from the most prominent of these
      trials and focuses on how the combination of cisplatin and etoposide has been
      evaluated for use in the adjuvant setting. Cisplatin-based therapy has now been
      shown to provide a significant survival benefit in several trials and recent meta
      analyses. These data have changed the paradigm for how early-stage lung cancer is
      managed.

PMID- 16813728
TI  - Small cell lung cancer clinical practice guidelines in oncology.

PMID- 16813729
TI  - Pulmonary neuroendocrine tumors: What (little) do we know?
AB  - Pulmonary neuroendocrine tumors are a distinct subset of tumors composing
      approximately 20% of all lung cancers. The major categories of pulmonary
      neuroendocrine tumors include typical and atypical carcinoids, large cell
      neuroendocrine carcinoma, and the more common small cell lung cancer. They are
      classified into different categories in the 2004 World Health Organization
      system, but share structural and morphologic features. Despite these shared
      features, their clinical characteristics range from indolent to aggressive, and
      therefore the approach to treatment depends on the histologic subtype. This
      article discusses the current understanding of the epidemiology, pathologic
      characteristics, treatment, and prognosis of this spectrum of diseases.

PMID- 16813730
TI  - Paraneoplastic syndromes associated with small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is the most frequent cancer histology associated
      with paraneoplastic syndromes. These syndromes are typically caused by ectopic
      hormone production or immune-mediated tissue destruction caused by neural antigen
      expression from cancer cells. This antigen expression induces the production of
      antibodies that cross-react with neural tissue. This article discusses the most
      common ectopic hormone and neurologic paraneoplastic syndromes and emphasizes the
      relationships among antigens, clinical syndromes, and outcomes. Although ectopic
      hormone production has been associated with extensive-stage disease and a poorer
      outcome, the antibody-mediated paraneoplastic syndromes are prognostic factors
      associated with more favorable outcomes. Both have the potential for improvement
      with cancer treatment.

PMID- 16813731
TI  - HER2 testing in breast cancer: NCCN Task Force report and recommendations.
AB  - The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically
      evaluate the ability of the level of HER2 expression or gene amplification in
      breast cancer tumors to serve as a prognostic and a predictive factor in the
      metastatic and adjuvant settings, to assess the reliability of the methods of
      measuring HER2 expression or gene amplification in the laboratory, and to make
      recommendations regarding the interpretation of test results. The Task Force is a
      multidisciplinary panel of 24 experts in breast cancer representing the
      disciplines of medical oncology, pathology, radiation oncology, surgical
      oncology, epidemiology, and patient advocacy. Invited members included members of
      the NCCN Breast Cancer Panel and other needed experts selected solely by the
      NCCN. During a 2-day meeting, individual task force members provided didactic
      presentations critically evaluating important aspects of HER2 biology and
      epidemiology: HER2 as a prognostic and predictive factor; results from clinical
      trials in which trastuzumab was used as a targeted therapy against HER2 in the
      adjuvant and metastatic settings; the available testing methodologies for HER2,
      including sensitivity, specificity, and ability to provide prognostic and
      predictive information; and the principles on which HER2 testing should be based.
      Each task force member was charged with identifying evidence relevant to their
      specific expertise and presentation. Following the presentations, an evidence
      based consensus approach was used to formulate recommendations relating to the
      pathologic and clinical application of the evidence to breast cancer patient
      evaluation and care. In areas of controversy, this process extended beyond the
      meeting to achieve consensus. The Task Force concluded that accurate assignment
      of the HER2 status of invasive breast cancer is essential to clinical decision
      making in the treatment of breast cancer in both adjuvant and metastatic
      settings. Formal validation and concordance testing should be performed and
      reported by laboratories performing HER2 testing for clinical purposes. If
      appropriate quality control/assurance procedures are in place, either
      immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods
      may be used. A tumor with an IHC score of 0 or 1+, an average HER2
      gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene
      copies/cell of 4 or less as determined by FISH is considered to be HER2 negative.
      A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of
      greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or
      greater is considered HER2 positive. A tumor with an IHC score of 2+ should be
      further tested using FISH, with HER2 status determined by the FISH result. Tumor
      samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average
      number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are
      considered to be borderline, and strategies to assign the HER2 status of such
      samples are proposed.

PMID- 16813733
TI  - Statement of the problem.
AB  - The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study
      poses 2 questions. Of the options in treating the hyperglycemia of type 2
      diabetes mellitus, which, if either, would be best for decreasing the likelihood
      of death or a serious cardiovascular disease event such as a heart attack:
      correcting the relative insulin deficiency or reducing insulin resistance? Do
      individuals with diabetes whose coronary disease can be managed medically have a
      better outcome with initial medical or interventional (percutaneous intervention
      or coronary artery bypass grafting) treatment? This article outlines the reasons
      for asking these questions.

PMID- 16813734
TI  - Hypotheses, design, and methods for the Bypass Angioplasty Revascularization
      Investigation 2 Diabetes (BARI 2D) Trial.
AB  - The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) is a
      National Institutes of Health (NIH)-sponsored randomized clinical trial that
      evaluates treatment efficacy for patients with type 2 diabetes mellitus and
      angiographically documented stable coronary artery disease. Using a 2 x 2
      factorial design, BARI 2D compares revascularization combined with aggressive
      medical treatment versus aggressive medical treatment alone; simultaneously, BARI
      2D compares 2 glycemic control strategies, insulin sensitization versus insulin
      provision. All patients have goals of glycosylated hemoglobin values <7.0% and
      uniform control of hypertension, dyslipidemia, and obesity following recommended
      medical guidelines. The primary end point of BARI 2D is all-cause 5-year
      mortality analyzed by intention to treat, and the principal secondary end point
      is the combination of death, myocardial infarction, and stroke. A total of 2,368
      patients have been enrolled at 49 clinical centers throughout North America,
      South America, and Europe. The study enrollment period was January 2001 through
      March 2005, and the patient treatment and follow-up phase is expected to extend
      at least through May 2007. Participants are treated at the local BARI 2D clinical
      sites on a monthly basis for the first 6 months and then every 3 months until the
      end of the study. Within BARI 2D, central management centers oversee the control
      of glycemia, plasma lipid levels, hypertension, and obesity. The randomized
      clinical trial collects data on patient symptoms, clinical measurements,
      medications, and clinical events as well as data from centralized evaluations of
      angiograms, electrocardiograms, nuclear stress tests, blood and urine specimens,
      and relative economic costs.

PMID- 16813735
TI  - Rationale, design, and methods for glycemic control in the Bypass Angioplasty
      Revascularization Investigation 2 Diabetes (BARI 2D) Trial.
AB  - A major therapeutic question in considering accelerated atherogenesis in patients
      with type 2 diabetes mellitus is whether reducing insulin resistance, as a
      proximal defect of a host of proatherogenic abnormalities including
      hyperglycemia, will be superior for decreasing mortality and coronary artery
      disease (CAD) risk compared with treating hyperglycemia to overcome insulin
      resistance with insulin-providing agents. This question is highly relevant, since
      earlier targeted glycemic control trials utilizing conventional glucose-lowering
      strategies that increase insulin levels have generally failed to reduce CAD risk
      despite markedly reducing microvascular risk. The Bypass Angioplasty
      Revascularization Investigation 2 Diabetes (BARI 2D) trial seeks to determine
      whether primarily using an insulin-sensitizing strategy for treatment of type 2
      diabetes is superior when compared with primarily using an insulin-providing
      strategy with regard to cardiovascular outcomes. This article presents the
      rationale, design, and methods being used to test the glycemic control hypothesis
      in BARI 2D.

PMID- 16813736
TI  - Rationale for the revascularization arm of the Bypass Angioplasty
      Revascularization Investigation 2 Diabetes (BARI 2D) Trial.
AB  - Modern coronary revascularization therapies, coronary artery bypass graft (CABG)
      surgery and percutaneous coronary intervention (PCI), continue to evolve and are
      widely applied. However, for patients with mild stable angina, or those who are
      asymptomatic with angiographically documented coronary artery disease (CAD), no
      survival benefit or reduction in the incidence of myocardial infarction has been
      demonstrated with CABG or PCI, except in the case of subgroups with
      angiographically determined high risk due to extensive multivessel disease with
      depressed LV function or left main CAD. At the same time, medical therapy
      continues to advance, with demonstrable benefit in both primary and secondary
      prevention of atherosclerotic coronary disease events. Patients with type 2
      diabetes mellitus, at increased risk for adverse cardiac events, have been shown
      to benefit from these approaches as well. However, in asymptomatic or mildly
      symptomatic patients with documented ischemia and angiographically significant
      CAD, the incremental benefit-or hazard-associated with early revascularization
      superimposed on aggressive medical and risk factor modification therapies is
      unknown. We discuss the background and rationale for investigating the impact of
      early revascularization in patients with diabetes and CAD.

PMID- 16813738
TI  - Ancillary studies in the Bypass Angioplasty Revascularization Investigation 2
      Diabetes (BARI 2D) Trial: Synergies and opportunities.
AB  - The definitive power of randomized controlled trials (RCTs) to characterize the
      efficacy of putative therapeutic approaches cannot be overestimated. Such trials
      are expensive, and their implementation requires prolonged and intensive
      commitments by both investigators and subjects. Accordingly, enhancing their
      value, in a sense increasing the "scientific return on investment," is a
      laudatory objective. Ancillary studies afford a great opportunity to do so. They
      permit acquisition of new knowledge, elucidation of cause/consequence relation,
      and delineation of pathogenetic mechanisms at a much lower cost than would be
      possible if they were performed independently of the parent RCTs. In addition,
      their utility is enhanced by internal consistency under the rubric of the parent
      trial and the presumed external validation of the parent trial. Several ancillary
      studies undertaken in conjunction with the Bypass Angioplasty Revascularization
      Investigation 2 Diabetes (BARI 2D) trial provide cogent examples. They seek to
      delineate causal connections linking the accelerated coronary disease typical of
      diabetes with phenomena such as genetic predisposition to altered expression of
      cytokines and fibrinolytic system proteins, inflammation, procoagulation, insulin
      induced impairment of fibrinolysis, insulin resistance, and the response to
      insulin-sensitizing and insulin-providing treatment strategies.

PMID- 16813737
TI  - Modifications of coronary risk factors.
AB  - In addition to the revascularization and glycemic management interventions
      assigned at random, the Bypass Angioplasty Revascularization Investigation 2
      Diabetes (BARI 2D) design includes the uniform control of major coronary artery
      disease risk factors, including dyslipidemia, hypertension, smoking, central
      obesity, and sedentary lifestyle. Target levels for risk factors were adjusted
      throughout the trial to comply with changes in recommended clinical practice
      guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59
      mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma
      triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg
      systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active
      smokers. Algorithms were developed for the pharmacologic management of
      dyslipidemia and hypertension. Dietary prescriptions for the management of
      glycemia, plasma lipid profiles, and blood pressure levels were adapted from
      existing clinical practice guidelines. Patients with a body mass index >25 were
      prescribed moderate caloric restriction; after the trial was under way, a
      lifestyle weight-management program was instituted. All patients were formally
      prescribed both endurance and resistance/flexibility exercises, individually
      adapted to their level of disability and fitness. Pedometers were distributed as
      a biofeedback strategy. Strategies to achieve the goals for risk factors were
      designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and
      nonpharmacologic intervention) and the ongoing implementation of the strategies
      is monitored by lipid, hypertension, and lifestyle intervention management
      centers.

PMID- 16813739
TI  - Economic evaluation of alternative strategies to treat patients with diabetes
      mellitus and coronary artery disease.
AB  - Diabetes mellitus and coronary artery disease (CAD) commonly coexist, and thus
      effective, cost-effective management strategies are needed. Intensive management
      of diabetes has been shown to increase medical costs while yielding better
      outcomes, with an acceptable cost-effectiveness ratio of <50,000 dollars per life
      year added. On the basis of clinical trial findings in the 1970s and 1980s,
      coronary bypass surgery was cost-effective compared with medical therapy in the
      treatment of extensive CAD. Few trials have compared angioplasty with medical
      therapy, and its cost-effectiveness is not well established. The economic
      outcomes of contemporary coronary revascularization, especially angioplasty,
      compared with contemporary medical therapy must be evaluated. The Bypass
      Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial will
      collect extensive economic data and examine the cost-effectiveness of alternative
      strategies to manage diabetes and CAD in patients with both disorders.

PMID- 16813740
TI  - What is the role of fetal nasal bone examination in the assessment of risk for
      trisomy 21 in clinical practice?

PMID- 16813741
TI  - HSV neutralizing antibodies further refinement in preventing neonatal Herpes
      infection.

PMID- 16813742
TI  - Shared and disparate components of the pathophysiologies of fetal growth
      restriction and preeclampsia.
AB  - Intrauterine growth restriction (IUGR) and preeclampsia differ in their
      association with maternal disease but share a similar placental pathology.
      Moreover, mothers who have had pregnancies complicated by preeclampsia or IUGR
      are at elevated later-life cardiovascular risk. Why, then, do some women develop
      IUGR and others develop preeclampsia? In this clinical opinion, based on a review
      of the literature, we hypothesize that both women experiencing preeclampsia and
      IUGR enter pregnancy with some degree of endothelial dysfunction, a lesion that
      predisposes to shallow placentation. In our opinion, preeclampsia develops when
      abnormal placentation, through the mediator of elevated circulating cytokines,
      interacts with maternal metabolic syndrome, comprised of adiposity, insulin
      resistance/hyperglycemia, hyperlipidemia, and coagulopathy. IUGR develops in the
      absence of antenatal metabolic syndrome. Among these women, the baby is affected
      by shallow placentation but the mother does not develop clinically apparent
      disease. This conceptualization provides a testable framework for future
      etiologic studies of preeclampsia and IUGR.

PMID- 16813743
TI  - Patterns of constipation in urogynecology: clinical importance and
      pathophysiologic insights.
AB  - OBJECTIVE: We have analyzed the prevalence and patterns of constipation in women
      with urinary symptoms and/or genital prolapse. STUDY DESIGN: Seven hundred and
      eighty-six consecutive urogynecologic patients underwent a questionnaire and
      structured clinical assessment. Comparison between constipated and nonconstipated
      women was made. Fisher exact test, Wilcoxon rank sum test, and logistic
      regression were used for statistical analysis (P < .05 for significance).
      RESULTS: Thirty-two percent of women were constipated (172 difficult stool
      passage, 13 reduced stool frequency, 64 both). A genital prolapse > or = 2 degree
      Half Way System (HWS) was present in 44% of women. A posterior colpocele was more
      frequent in constipated women (35% vs 19%; P < .0001), resulting in a risk factor
      for constipation (OR 2.31; 95% CI 1.63-3.27). By contrast, higher degrees of
      anterior colpocele appeared to protect against constipation (OR 0.80; 95% CI 0.66
      0.96). No differences in prevalence of constipation were observed for urinary
      symptoms or urodynamic diagnosis. CONCLUSION: Bowel dysfunction correlates
      exclusively with posterior aspects of the pelvic floor support.

PMID- 16813744
TI  - Neovaginal mucosa after Vecchietti's laparoscopic operation for Rokitansky
      syndrome: structural and ultrastructural study.
AB  - OBJECTIVE: This study was undertaken to evaluate structural and ultrastructural
      characteristics of the mucosa of neovaginae created by Vecchietti's laparoscopic
      operation for Rokitansky syndrome. STUDY DESIGN: Vaginoscopy and Schiller test
      were performed 3, 6, and 12 months after the operation in 106 patients. A biopsy
      specimen of the neovagina obtained 12 to 18 months after surgery in 19 patients
      was examined by light, scanning electron, and transmission electron microscopy.
      RESULTS: At vaginoscopy, the neovaginal mucosa appeared smooth, lacking the folds
      that characterize the normal vagina; 12 months after the operation, an iodium
      positive epithelium was present in all neovaginae. Mild ultrastructural
      modifications, as compared with normal vaginal mucosa, were reduced maturation,
      inflammatory infiltration, and tendency to superficial desquamation. CONCLUSION:
      At a 12-month follow-up, the mucosa of neovaginae created by the Vecchietti
      technique is comparable to the normal vaginal mucosa, with mild structural and
      ultrastructural modifications that we believe might be due to reduced
      vascularization.

PMID- 16813745
TI  - Postmenopausal hormone therapy increases use of health services: experience from
      the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757].
AB  - OBJECTIVE: This study was undertaken to compare utilization of health services
      and health care costs in a randomized hormone therapy trial. STUDY DESIGN: A
      total of 1823 healthy postmenopausal women aged 50 to 64 years at the time of
      sampling were allocated to combined continuous hormone therapy or placebo or no
      treatment. The analysis was based on routinely collected electronic data in the
      Estonian Health Insurance Fund database during a follow-up period from 2 to 5
      years. RESULTS: In the nonblind subtrial, the number of all health care visits
      was 10% higher and the number of visits to family practitioners 16% higher per
      person-year in the hormone therapy arm. Per person-year, the number of vaginal
      sonograms was 14% and the number of electrocardiograms 19% higher in the nonblind
      hormone therapy arm. Outpatient health care costs and drug expenses were higher
      in the nonblind hormone therapy arm. In the blind subtrial, the number of
      gynecologic operations, vaginal sonograms and total health care costs was higher
      in the hormone therapy arm. CONCLUSION: Hormone therapy caused additional
      expenses on health care.

PMID- 16813746
TI  - Impact of an adolescent sex education program that was implemented by an academic
      medical center.
AB  - OBJECTIVE: The purpose of this study was to assess changes in knowledge and
      attitudes before and after a large-scale sex education curriculum that was
      implemented by an academic medical center. STUDY DESIGN: Middle school students
      were surveyed regarding demographics, knowledge, attitudes, and behaviors. All
      grade levels at each campus completed a presurvey on the same day before any of
      the 2-week curricula were received. Postsurveys were taken on the day after the
      last lesson. RESULTS: Surveys were completed by 26,125 students before and 24,550
      students after a sex education curriculum. Knowledge improved (P < .001) for all
      grades, based on paired comparisons for each group. Although most students chose
      the option to wait until after high school graduation to have sex, significantly
      more students held this opinion after the program (P < .0001). Variables that
      were associated with the attitude of delaying sex included making a pledge (odds
      ratio, 7.4; 95% CI, 6.7-8.2), original parents still married (odds ratio, 1.6;
      95% CI, 1.1-2.1), attending weekly religious/church services (odds ratio, 1.5;
      95% CI, 1.3-1.6), and watching 0 to 2 hours of television on school nights (odds
      ratio, 1.4; 95% CI, 1.2-1.5). Self-reported "less than C" students showed the
      least knowledge improvement and the belief that teens should "have sex whenever
      they want" at a greater percentage than other academic levels. CONCLUSION:
      Implementation of a sex education curriculum by an academic medical center to
      adolescents resulted in increased knowledge and a shift in attitude toward
      delaying sexual activity.

PMID- 16813747
TI  - Long-term safety of an extended-cycle oral contraceptive (Seasonale): a 2-year
      multicenter open-label extension trial.
AB  - OBJECTIVE: The purpose of this study was to assess the long-term safety of
      Seasonale, 91-day extended-cycle oral contraceptive (OC). STUDY DESIGN: Following
      completion of a 1-year Phase 3 multicenter trial, patients from selected centers
      were invited to participate in this 2-year extension trial. In this open-label
      study all participants received the 91-day extended-regimen OC, Seasonale.
      RESULTS: There were 189 study participants enrolled from 27 sites. Patient
      exposure included 1130 completed 91-day cycles. Overall rates of study
      discontinuation and the incidence of adverse events were similar to the earlier
      Phase 3 clinical trial. Seasonale was well tolerated and the number of reported
      bleeding and/or spotting days reported diminished during the course of the study.
      CONCLUSION: This study confirms the findings from the previous clinical trial and
      demonstrates that Seasonale is a safe and effective therapy for long-term use.

PMID- 16813748
TI  - Effects of tibolone on nuclear receptors in human endometrial cells.
AB  - OBJECTIVE: Tibolone regulates estrogenic activity in a tissue-selective manner.
      The purpose of this study was to evaluate the effects of tibolone on the mRNA
      content of nuclear receptors, estrogen receptor-alpha and beta (ERalpha and
      ERbeta), progesterone receptor (PR), and androgen receptor (AR) in human
      endometrial stromal and glandular cells. STUDY DESIGN: Human endometrial stromal
      and glandular cells were isolated from endometrial tissue fragments and
      separately incubated with tibolone and its metabolites. Nuclear receptor mRNA was
      determined using real-time polymerase chain reaction (PCR). RESULTS: In
      endometrial stromal cells, tibolone, Delta4-tibolone, and 3betaOH-tibolone, but
      not 3alphaOH-tibolone, significantly reduced ERalpha mRNA by approximately 60%
      and ERalpha protein by approximately 80%. No reduction of ERalpha was observed in
      endometrial glandular cells. Tibolone induced PR mRNAs to various extents and
      reached up to 6-fold in glandular cells, but only a moderate increase
      (approximately 1.5-fold) in stromal cells. Tibolone increased ERbeta and had
      little effect on AR mRNA in endometrial cells. CONCLUSION: The results showed the
      majority of the nuclear receptors were not significantly altered. However,
      tibolone significantly reduced ERalpha in stromal cells and increased PR in
      glandular cells. These biological effects may play essential roles in averting
      stimulation of the endometrium in tibolone users.

PMID- 16813749
TI  - Nasal bone in first-trimester screening for trisomy 21.
AB  - OBJECTIVE: This study was undertaken to investigate the impact of incorporating
      assessment of the nasal bone into first-trimester combined screening by fetal
      nuchal translucency (NT) thickness and maternal serum biochemistry. STUDY DESIGN:
      In this prospective combined screening study for trisomy 21, the fetal nasal bone
      was also examined and classified as present or absent. A multivariate approach
      was used to calculate patient-specific risks for trisomy 21 and the detection
      rate (DR) and false-positive rate (FPR) were estimated. We examined 2 screening
      strategies; first, integrated first-trimester screening in all patients and
      second, first-stage screening of all patients using fetal NT and maternal serum
      free beta-hCG and PAPP-A, followed by second-stage assessment of nasal bone only
      in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first
      stage. RESULTS: The nasal bone was absent in 113 (0.6%) of the 20,165
      chromosomally or phenotypically normal fetuses and in 87 (62.1%) of the 140
      fetuses with trisomy 21. With combined first-trimester NT and serum screening,
      the DR of 90% was achieved at a FPR of 5%. Inclusion of the nasal bone, either in
      all cases or in about 10% of the total in the 2-stage approach, halved the FPR to
      2.5%. CONCLUSION: Inclusion of the nasal bone in first-trimester combined
      screening for trisomy 21 achieves a DR of 90% for a FPR of 2.5%.

PMID- 16813750
TI  - Maternal herpes simplex virus antibody avidity and risk of neonatal herpes.
AB  - OBJECTIVE: The objective of the study was to assess whether herpes simplex virus
      antibody avidity is associated with risk of transmission of herpes simplex virus
      to the neonate. STUDY DESIGN: We developed a novel herpes simplex virus type 1
      avidity test based on the commercially available Focus HerpeSelect-1 enzyme
      linked immunosorbent assay kit using sera from nonpregnant subjects with genital
      herpes simplex virus-1 infection. We used this test, and the previously developed
      herpes simplex virus type 2 avidity test, to compare maternal herpes simplex
      virus-1 and herpes simplex virus-2 antibody avidity in women who transmitted
      herpes simplex virus to the neonate and women who had herpes simplex virus
      isolated from genital secretions at delivery but who did not transmit herpes
      simplex virus to their infants. RESULTS: Among nonpregnant subjects with genital
      herpes simplex virus-1 infection whose sera were used to develop the herpes
      simplex virus-1 avidity test, a significant relationship between herpes simplex
      virus-1 antibody avidity and time since herpes simplex virus-1 acquisition was
      observed (P < .001, mixed-effects model), with median avidity values increasing
      over time after primary infection. Among pregnant, herpes simplex virus-1, or
      herpes simplex virus-2 seropositive women, 4 of 8 women (50%) with avidity 40 or
      greater transmitted herpes simplex virus to the neonate, compared with only 12 of
      97 (12%) of women with avidity greater than 40 (P = .02). CONCLUSIONS: Herpes
      simplex virus-1 antibody avidity increased over time after genital herpes simplex
      virus-1 acquisition, as has been previously observed for herpes simplex virus-2.
      Among women with herpes simplex virus antibody at delivery, low antibody avidity
      was associated with herpes simplex virus transmission to the neonate and may be a
      useful marker for recent seroconversion.

PMID- 16813751
TI  - Intimate partner violence victimization prior to and during pregnancy among women
      residing in 26 U.S. states: associations with maternal and neonatal health.
AB  - OBJECTIVE: To conduct a population-based assessment of associations of intimate
      partner violence in the year prior to and during pregnancy with maternal and
      neonatal morbidity. STUDY DESIGN: Data from women giving birth in 26 U.S. states
      and participating in the 2000 to 2003 Pregnancy Risk Assessment Monitoring System
      (n = 118,579) were analyzed. RESULTS: Women reporting intimate partner violence
      in the year prior to pregnancy were at increased risk for high blood pressure or
      edema (adjusted odds ratio 1.37-1.40), vaginal bleeding (adjusted odds ratio 1.54
      1.66), severe nausea, vomiting or dehydration (adjusted odds ratio 1.48-1.63),
      kidney infection or urinary tract infection (adjusted odds ratio 1.43-1.55),
      hospital visits related to such morbidity (adjusted odds ratio 1.45-1.48), and
      delivery preterm (adjusted odds ratio 1.37), of a low-birthweight infant
      (adjusted odds ratio 1.17), and an infant requiring intensive care unit care
      (adjusted odds ratio 1.31-1.33) compared with those not reporting intimate
      partner violence. Women reporting intimate partner violence during but not prior
      to pregnancy experienced higher rates of a subset of these concerns. CONCLUSION:
      Women experiencing intimate partner violence both prior to and during pregnancy
      are at risk for multiple poor maternal and infant health outcomes, suggesting
      prenatal risks to children from mothers' abusive partners.

PMID- 16813752
TI  - Fetal growth and onset of delivery: a nationwide population-based study of
      preterm infants.
AB  - OBJECTIVE: This study was undertaken to assess whether deviations from normal
      fetal growth are associated with spontaneous preterm delivery. STUDY DESIGN: A
      population-based study was performed, using Swedish Medical Birth Register data
      from 1991 through 2001. The total population comprised 1,007,648 singleton
      births. Intrauterine-derived growth standards were used to identify individual
      standard deviation (SD) from expected birth weight. Spontaneous preterm infants
      were compared with infants born after spontaneous labor at term. Results were
      obtained by using multiple logistic regression analysis. RESULTS: Associations
      between smaller than population mean and spontaneous preterm birth were evident
      for all gestational age groups. The largest risk was found at 28 to 31
      gestational weeks and birth weight less than -3 SD (OR: 13.3; 95% CI: 10.3-17.2).
      Spontaneous preterm infants born at 34 to 36 gestational weeks weighed 1 to 1.9
      SD (OR: 1.1; 95% CI: 1.1-1.2) or 2 to 2.9 SD (OR: 1.6; 95% CI: 1.5-1.7) above the
      expected mean more often. CONCLUSION: Deviation of fetal growth from the expected
      mean is associated with spontaneous preterm delivery.

PMID- 16813753
TI  - Should phosphodiesterase 5 selective inhibitors be used for uterine relaxation?
AB  - Sildenafil citrate is a phosphodiesterase 5-selective inhibitor used successfully
      in treating erectile dysfunction. High doses of sildenafil can inhibit myometrial
      contractions. However, no study has demonstrated a role for phosphodiesterase 5
      in myometrial contractility. No clinical trial using sildenafil to promote
      uterine relaxation should be initiated based on the currently available data.

PMID- 16813754
TI  - Long-term neurodevelopmental outcome and brain volume after treatment for hydrops
      fetalis by in utero intravascular transfusion.
AB  - OBJECTIVE: We tested the hypothesis that long-term neurodevelopmental outcomes of
      successfully treated fetuses with immune hydrops are similar to their unaffected
      siblings according to a protocol that addresses the underlying pathophysiologic
      condition. STUDY DESIGN: Sixteen of 18 consecutive hydropic fetuses (89%) who
      were treated in a dedicated fetal medicine unit between July 1985 and October
      1995 survived. The transfusion protocol used a 2-step correction over a 2 to 4
      day interval, combined with umbilical venous pressure measurements to avoid over
      transfusion and bicarbonate administration to assure a posttransfusion UV pH of
      >7.30. Survivors were evaluated at a mean age of 10 years. Statistical analyses
      included t-test, Wilcoxon rank-sum test, Fisher's exact test, and Pearson
      coefficients. RESULTS: Overall, death or major neurologic morbidity occurred in 4
      of 18 of the fetuses (22%) who were treated (2/16 of survivors [12.5%]). Among
      the survivors, the children with immune hydrops had physical, neurologic, and
      cognitive outcomes statistically similar to their siblings, except for a measure
      of visual attention. Two of the children (12%) had major neurologic sequelae.
      Brain volumes were statistically smaller than unrelated control subjects by 8.8%,
      but these control subjects were not matched for height at testing or gestational
      age at birth. Both groups had brain volumes within the normal range. CONCLUSION:
      Intravascular transfusion of fetuses with profoundly anemic immune hydrops
      results in high survival rates and favorable long-term neuropsychological
      outcomes.

PMID- 16813755
TI  - Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal
      sheep.
AB  - OBJECTIVE: Erythropoietin is present in human amniotic fluid and has been
      suggested as a marker of fetal hypoxia. The objectives of the present study were
      to determine whether erythropoietin is present in ovine amniotic fluid, fetal
      urine, and/or lung liquid and whether concentrations in these compartments change
      in parallel with endogenous fetal plasma erythropoietin concentration when the
      latter is increased experimentally. STUDY DESIGN: In late gestation chronically
      catheterized fetal sheep, samples of amniotic fluid and plasma, urine and plasma,
      lung liquid, amniotic fluid, and plasma were collected before and up to 7 days
      after induction of 4 types of fetal hypoxia: (1) acute anemic hypoxia that was
      induced by a single fetal hemorrhage, (2) progressive anemic hypoxia that was
      induced by daily exchange transfusion, (3) acute hypoxic hypoxia that was induced
      by the reduction of maternal inspired oxygen content, or (4) chronic placental
      insufficiency that was induced by daily umbilicoplacental embolization for 4
      days. Erythropoietin concentrations were determined by radioimmunoassay.
      Statistical testing included analysis of variance and least squares regression.
      RESULTS: Under basal, nonhypoxic conditions, amniotic fluid erythropoietin
      concentration averaged 33.2% +/- 1.6% (SE) of fetal plasma erythropoietin
      concentration, and basal fetal urine and lung liquid erythropoietin
      concentrations ranged from low (<10% of plasma concentration) to nondetectable.
      Unlike the strong correlation in humans, basal amniotic fluid and plasma
      erythropoietin concentrations were correlated only weakly (r = 0.259; r2 = 6.7%;
      P = .0027; n = 132). Amniotic fluid erythropoietin concentration approximately
      doubled after 12 hours of severe hypoxic hypoxia or after 24 hours of
      embolization-induced severe hypoxia but was unchanged after 12 hours of mild
      moderate hypoxic hypoxia or 24 hours of anemic hypoxia. Concomitant fetal plasma
      erythropoietin concentrations increased to 28.1 +/- 5.3, 12.5 +/- 2.7, 10.8 +/-
      4.6, and 10.0 +/- 1.3 times basal values, respectively. During progressive fetal
      anemia, urinary erythropoietin concentration increased almost 10-fold (P = .0023)
      but remained a small fraction (3.7% +/- 0.4%) of plasma concentration; at 12
      hours of hypoxic hypoxia, lung liquid erythropoietin concentration did not vary
      with the severity of the hypoxia and remained low relative to plasma
      concentration (4.2% +/- 2.1%). CONCLUSION: Erythropoietin is present in ovine
      amniotic fluid, urine, and lung liquid. With only 3 potential sources, the fetal
      membranes appear to be the primary source of amniotic fluid erythropoietin in the
      nonhypoxic ovine fetus because basal urine and lung liquid erythropoietin
      concentrations are much lower than amniotic fluid concentrations. Although
      unchanged during mild-to-moderate fetal hypoxia, amniotic fluid erythropoietin
      concentration increases modestly during severe fetal hypoxia. In sheep, fetal
      urinary erythropoietin may contribute to this rise in amniotic fluid
      erythropoietin concentration during severe hypoxia, because fetal urinary and
      plasma concentrations increase in parallel during anemia.

PMID- 16813756
TI  - Evaluation of placenta growth factor and soluble Fms-like tyrosine kinase 1
      receptor levels in mild and severe preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine if maternal serum
      concentrations of placenta growth factor (PlGF) and soluble Fms-like tyrosine
      kinase 1 receptor (s-Flt1) are more abnormal in patients with severe preeclampsia
      compared with mild preeclampsia. STUDY DESIGN: Serum samples were collected from
      32 control patients and 80 patients with mild or severe preeclampsia. PlGF and s
      Flt1 concentrations were quantitated by enzyme-linked immunosorbent assay
      (ELISA). Results are expressed as median (Q1-Q3) unless stated otherwise. After
      normalization, serum markers were compared using one-way analysis of covariance
      (ANCOVA). RESULTS: Patients with preeclampsia had decreased levels of PlGF (75.1
      +/- 14 vs 391 +/- 54 pg/mL, P < .0001) and elevated s-Flt1 concentration (1081 +/
      108 vs 100.1 +/- 26.9 pg/mL, P < .0001) compared with the respective controls
      (mean +/- SEM). PlGF concentration was lower in patients with mild preeclampsia
      compared with severe, respectively (67 pg/mL [39-158] vs 24 pg/mL [4-57], P <
      .02). s-Flt1 was not different between mild and severe preeclampsia (674 pg/mL
      [211-1297] vs 1015 pg/mL [731-1948], P = .08). CONCLUSION: PlGF and s-Flt1 serum
      levels are abnormal in patients with preeclampsia compared with controls, but
      only PlGF is more abnormal in severe preeclampsia compared with mild
      preeclampsia.

PMID- 16813757
TI  - A "top-down-approach" to insert catheters into the circulation of fetal sheep
      using ultrasound B-scan.
AB  - OBJECTIVE: The objective of the study was the catheterization of vessels in fetal
      sheep under ultrasound control. STUDY DESIGN: A catheter with guiding wire was
      introduced into the external jugular vein or carotid artery and advanced
      caudally. RESULTS: The aorta and umbilical vein could be accessed. CONCLUSION:
      Major segments of the circulation are accessible from the neck for chronic
      instrumentation.

PMID- 16813758
TI  - Syncytiotrophoblastic vesicles in placental intervillous space.
AB  - OBJECTIVE: This study was undertaken to investigate the origin and function of
      vesicles found in the intervillous space. STUDY DESIGN: A retrospective study was
      performed by using placental sections of different gestational ages. The number
      of vesicles was counted in each section of gestational age groups.
      Immunohistochemical staining for beta-human chorionic gonadotropin (beta-hCG) and
      human placental lactogen (hPL) was conducted to confirm the origin of vesicles.
      RESULTS: Staining for beta-hCG and hPL was prominent in vesicles separating from
      syncytiotrophoblast into the intervillous space. The numbers of vesicles were not
      significantly different in gestational age groups of 42 to 30 weeks and all
      vesicles disappeared in 9- to 5-week groups. Large vesicles tended to show
      degeneration and disintegration in the intervillous space. CONCLUSION: The
      vesicles containing beta-hCG and hPL suggest a different secretory mechanism of
      syncytiotrophoblast.

PMID- 16813759
TI  - Primary uterine lymphoma: report of 2 cases and review of literature.
AB  - Primary uterine non-Hodgkin's lymphoma is a rare malignancy. We here describe 2
      patients who presented with cervical growth, stage IE, diffuse large B cell
      histology. Both were treated with chemotherapy followed by involved field
      radiotherapy in 1 patient. They achieved complete clinical and radiological
      response. Data of 101 patients collected from the literature are reviewed.

PMID- 16813760
TI  - Selective uterine artery embolization: a new therapeutic approach in a patient
      with low-risk gestational trophoblastic disease.
AB  - We report a case of persistent gestational trophoblastic disease (GTD) in which a
      selective uterine artery embolization instead of invasive surgery achieved both
      the control of pelvic hemorrhage and of disease.

PMID- 16813761
TI  - Nerve injury caused by removal of an implantable hormonal contraceptive.
AB  - Implanon insertion and removal are relatively uncomplicated procedures in the
      hands of medical professionals familiar with the technique. However, injury to
      branches of the medial antebrachial cutaneous nerve during Implanon insertion and
      removal can result in impaired sensibility, severe localized pain, or the
      formation of painful neuroma that can be quite devastating to the patient. The
      best way to avoid injury to the medial antebrachial cutaneous nerve is to better
      understand its position relative to the standard area of Implanon insertion. In
      the event that an injury to the nerve is recognized, immediate plastic surgical
      measures should be undertaken to avoid displeasing sequels of nerve injuries.
      Therefore, the benefit of this generally well-tolerated, highly effective, and
      relatively cost-efficient contraception is guaranteed only in the hands of
      medical professionals familiar with the technique.

PMID- 16813762
TI  - Prepubertal menarche: a defined clinical entity.
AB  - Prepubertal vaginal bleeding is considered as isolated menarche when, in the
      absence of detectable abnormality, it is not accompanied by any evidence of
      sexual development. The etiology remains unclear and various hypotheses have been
      put forward. This is the first time that a series of ultrasound patients with
      prepubertal menarche whose investigation has included imaging with ultrasound has
      been described. This paper illustrates isolated prepubertal menarche without the
      presence of an endometrial echo.

PMID- 16813763
TI  - Viral particles in endomyocardial biopsy tissue from peripartum cardiomyopathy
      patients.

PMID- 16813764
TI  - An integrated model for the prediction of pre-eclampsia using maternal factors
      and uterine artery Doppler velocimetry in unselected low-risk women.

PMID- 16813766
TI  - Association of intravenous oxytocin to vaginal misoprostol for mid trimester
      labor induction.

PMID- 16813768
TI  - Risk assessment and counseling service available for women with pregnancy
      exposures to medications.

PMID- 16813770
TI  - At times, the Atlantic can be very wide!

PMID- 16813773
TI  - Effects of exercise programs on falls and mobility in frail and pre-frail older
      adults: A multicenter randomized controlled trial.
AB  - OBJECTIVES: To determine the effects of moderate intensity group-exercise
      programs on falls, functional performance, and disability in older adults; and to
      investigate the influence of frailty on these effects. DESIGN: A 20-week,
      multicenter randomized controlled trial, with 52-week follow-up. SETTING: Fifteen
      homes for the elderly. PARTICIPANTS: Two hundred seventy-eight men and women
      (mean age +/- standard deviation, 85+/-6y). INTERVENTIONS: Two exercise programs
      were randomly distributed across 15 homes. The first program, functional walking
      (FW), consisted of exercises related to daily mobility activities. In the second
      program, in balance (IB), exercises were inspired by the principles of Tai Chi.
      Within each home participants were randomly assigned to an intervention or a
      control group. Participants in the control groups were asked not to change their
      usual pattern of activities. The intervention groups followed a 20-week exercise
      program with 1 meeting a week during the first 4 weeks and 2 meetings a week
      during the remaining weeks. MAIN OUTCOME MEASURES: Falls, Performance Oriented
      Mobility Assessment (POMA), physical performance score, and the Groningen
      Activity Restriction Scale (GARS) (measuring self-reported disability). RESULTS:
      Fall incidence rate was higher in the FW group (3.3 falls/y) compared with the IB
      (2.4 falls/y) and control (2.5 falls/y) groups, but this difference was not
      statistically significant. The risk of becoming a faller in the exercise groups
      increased significantly in the subgroup of participants who were classified as
      being frail (hazard ratio [HR] = 2.95; 95% confidence interval [CI], 1.64-5.32).
      For participants who were classified as being pre-frail, the risk of becoming a
      faller decreased; this effect became significant after 11 weeks of training (HR =
      .39; 95% CI, .18-.88). Participants in both exercise groups showed a small, but
      significant improvement in their POMA and physical performance scores. In the FW
      group, this held true for the GARS score as well. Post hoc analyses revealed that
      only the pre-frail participants improved their POMA and physical performance
      scores. CONCLUSIONS: Fall-preventive moderate intensity group-exercise programs
      have positive effects on falling and physical performance in pre-frail, but not
      in frail elderly.

PMID- 16813775
TI  - Vitamin D deficiency and osteoporosis in rehabilitation inpatients.
AB  - OBJECTIVE: To determine vitamin D status and bone mineral density (BMD) in
      patients admitted to a subacute rehabilitation facility. DESIGN: Cross-sectional
      cohort study. SETTING: Subacute rehabilitation facility. PARTICIPANTS: Fifty
      three community-dwelling patients admitted from June through February 2005.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: BMD, 25-hydroxyvitamin D
      (25[OH]D), C-telopeptide (CTX), osteocalcin, and dietary milk intake. RESULTS:
      Prevalence of vitamin D deficiency (25[OH]D <20 ng/mL) was 49.1%, while a total
      of 83% of patients were either vitamin D deficient or insufficient (25[OH]D <30
      ng/mL). The prevalence of osteopenia (T score, <-1) was 52.8%; osteoporosis (T
      score, <-2.5) was 17.0%. CTX (bone resorption marker) was elevated in 60.4% of
      patients. Osteocalcin (bone formation marker) was elevated in 13.2% of patients.
      Measurements of bone resorption and formation positively correlated (R2 = .22)
      indicating increased bone remodeling. CONCLUSIONS: Vitamin D deficiency and
      osteopenia and osteoporosis were highly prevalent in patients admitted for
      rehabilitation. Elevated bone resorption and remodeling were evident. This could
      be due to vitamin D deficiency that should be corrected before antiresorptive
      therapy is considered. The study emphasizes the need for vigilance for vitamin D
      status and BMD testing in patients admitted to rehabilitation facilities.

PMID- 16813774
TI  - Spinal stenosis, back pain, or no symptoms at all? A masked study comparing
      radiologic and electrodiagnostic diagnoses to the clinical impression.
AB  - OBJECTIVE: To assess the relations between clinically recognized lumbar spinal
      stenosis and the conclusions of masked radiologists and electrodiagnosticians.
      DESIGN: Prospective, masked, double-controlled trial. SETTING: University spine
      center. PARTICIPANTS: One hundred fifty persons age 55 to 80 years with or
      without back pain and with or without magnetic resonance imaging (MRI)
      demonstrated stenosis, screened for neuropathy risk, previous surgery, or cancer.
      INTERVENTIONS: Questionnaires on pain and function; ambulation testing and
      physical examination; and masked electrodiagnotics and MRI. MAIN OUTCOME MEASURE:
      Diagnostic impressions of the examining clinician, radiologist, and
      electrodiagnostician. RESULTS: Following application of post hoc exclusion
      criteria and elimination of patients due to incomplete or inadequate test data,
      the clinical diagnosis was lumbar stenosis in 50 subjects, back pain in 44
      subjects, and no pain in 32 subjects. Radiologic and clinical impression had no
      relation (P = .80 vs asymptomatic, P = .99 vs back pain controls).
      Electrodiagnostic impression trended to relate to clinical impression (P = .14 vs
      asymptomatic, P = .09 vs back pain). Retrospective application of age-related
      electrodiagnostic norms for paraspinal electromyographic and limb motor unit
      changes, established in this study, reclassified 13 of the 17 asymptomatic
      persons whom the electrodiagnostician thought had stenosis. The clinical
      impression did correspond to history and physical examination findings typically
      associated with spinal stenosis and to the independent impression of a
      neurosurgeon who examined MRI and clinical, but not to the electrodiagnostic
      data. CONCLUSIONS: The impression obtained from an MRI scan does not determine
      whether lumbar stenosis is a cause of pain. Electrodiagnostic consultation may be
      useful, especially if age-related norms obtained in this study are applied.

PMID- 16813776
TI  - Side effects and adverse events related to intraligamentous injection of
      sclerosing solutions (prolotherapy) for back and neck pain: A survey of
      practitioners.
AB  - OBJECTIVE: To study the side effects and adverse events related to
      intraligamentous injection of sclerosing solutions (prolotherapy) for back and
      neck pain. DESIGN: Practitioner postal survey. SETTING: Postal survey of
      practitioners of prolotherapy for back and neck pain in the United States and
      Canada. PARTICIPANTS: A sample of prolotherapy practitioners from 2 professional
      organizations were surveyed about their training and experience, use of specific
      treatment procedures, estimated prevalence of side effects, and adverse events
      related to prolotherapy for back and neck pain. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Prevalence of side effects and adverse events. RESULTS:
      Surveys were completed by 171 practitioners (response rate, 50%). Ninety-eight
      percent held medical degrees, and 83% were board certified in various
      disciplines. Respondents had a median of 10 years of experience, during which
      they had treated a median of 500 patients and given a median of 2000 treatments.
      Side effects with the highest median estimated prevalence were pain (70%),
      stiffness (25%), and bruising (5%). There were 472 reports of adverse events,
      including 69 that required hospitalization and 5 that resulted in permanent
      injury secondary to nerve injury. The vast majority (80%) were related to needle
      injuries such as spinal headache (n = 164), pneumothorax (n=123), temporary
      systemic reactions (n = 73), nerve damage (n = 54), hemorrhage (n = 27),
      nonsevere spinal cord insult (ie, meningitis, paralysis, spinal cord injury) (n =
      9), and disk injury (n = 2). CONCLUSIONS: Side effects related to prolotherapy
      for back and neck pain, such as temporary postinjection pain, stiffness, and
      bruising, are common and benign. Adverse events related to prolotherapy for back
      and neck pain are similar in nature to other widely used spinal injection
      procedures. Further study is needed to fully describe the adverse event profile
      of prolotherapy for back and neck pain.

PMID- 16813777
TI  - The relation between previous fractures and physical performance in elderly
      women.
AB  - OBJECTIVE: To examine the association between previous fracture and different
      aspects of physical performance. DESIGN: Population-based retrospective study.
      SETTING: Orthopaedic research department. PARTICIPANTS: Randomly selected women
      (N = 1044), all 75 years old and participants of the Malmo Osteoporosis
      Prospective Risk Assessment study. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Type of and time since any previous fracture event were compared with
      results of tests on physical performance function (Romberg test, computerized
      sway test, gait speed, questionnaire) at the age of 75. RESULTS: Women with no
      previous fractures (n = 505) had a better median Romberg balance of 94 seconds
      (interquartile range [IQR], 75-118s) than women with 1, 2, or 3 or more
      fractures, who had a median balance of 88 seconds (IQR, 71-111s), 85 seconds
      (IQR, 68-107s), and 81 seconds (IQR, 65-109s), respectively (Kruskal-Wallis
      analysis of variance, P = .002). Balance was inferior in women who had sustained
      a previous fracture between the ages of 65 and 75 years compared with women with
      no previous fractures or fractures before the age of 65 years. Gait speed and
      questions on tendency to fall followed the same pattern. The computerized sway
      test could not differ between women with and without previous fractures.
      CONCLUSIONS: Poor physical performance is associated with previous fractures.
      Inferior physical performance may exist up to 10 years after a fracture.

PMID- 16813778
TI  - Validity and reliability of the modified shuttle walk test in patients with
      chronic obstructive pulmonary disease.
AB  - OBJECTIVES: (1) To examine the concurrent criterion validity of the modified
      shuttle walk test (MSWT) by using the 6- (6MWT) and 12-minute walk test (12MWT),
      (2) to examine the concurrent criterion validity of the estimated maximum oxygen
      uptake (Vo2max) of the MSWT with actual Vo2max, and (3) to determine test-retest
      reliability of the MSWT in patients with chronic obstructive pulmonary disease
      (COPD). DESIGN: Validation study. SETTING: Outpatient pulmonary rehabilitation
      program. PARTICIPANTS: Thirty clinically stable adults with COPD. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Subjects were randomly assigned to receive
      either the 6MWT and 12MWT or the MSWT first. The MSWT was repeated 1 week later
      (N = 30). Estimated Vo2max was calculated, and actual Vo2max was conducted by
      using the Jones test. Validity of the MSWT was assessed by comparing endurance
      scores and Vo2max with results from the 6MWT and 12MWT and Jones test,
      respectively. RESULTS: There was a moderately high correlation between the MSWT
      and the 6MWT and 12MWT at initial testing (.82 and .74, respectively).
      Correlation between estimated and actual Vo2max was r equal to .68. Test-retest
      reliability for the entire sample was high (intraclass correlation coefficient,
      .88). Results remained quite stable across severity, age, and sex subgroups.
      CONCLUSIONS: The MSWT is a standardized externally paced submaximal endurance
      walking test. The results indicate that the MSWT has high concurrent validity and
      test-retest reliability for patients with COPD.

PMID- 16813779
TI  - Electromyographic activity in the immobilized shoulder girdle musculature during
      scapulothoracic exercises.
AB  - OBJECTIVE: To quantify the electromyographic activity in the shoulder girdle
      musculature during scapulothoracic exercises performed in a shoulder immobilizer
      in asymptomatic men. DESIGN: Descriptive. SETTING: Motion analysis laboratory at
      a tertiary care center. PARTICIPANTS: Five asymptomatic male volunteers ages 24
      to 32 years. INTERVENTION: Fine-wire (supraspinatus, infraspinatus, upper
      subscapularis) and surface (deltoids, trapezii, biceps, serratus anterior)
      electrodes recorded electromyographic activity from each muscle during scapular
      clock, elevation, depression, protraction, and retraction exercises completed
      during a single testing session in random order. MAIN OUTCOME MEASURE: Mean peak
      normalized (percentage of maximal voluntary contraction [MVC]) electromyographic
      activity of each muscle during each exercise. RESULTS: Biceps activity was
      uniformly low (<20% MVC), whereas upper subscapularis activity was uniformly high
      (40%-63% MVC). Both scapular depression and protraction elicited low activity
      (<20% MVC) in the supraspinatus, infraspinatus, anterior deltoid, and biceps
      brachii muscles, while generally producing greater than 20% MVC activity in the
      trapezii and serratus. Scapular depression produced the largest serratus anterior
      activity (47% MVC). CONCLUSIONS: These data are the first to describe the
      electromyographic activity during scapulothoracic exercises while in a shoulder
      immobilizer. Based on electrophysiologic data in normal volunteers, our findings
      suggest that during periods of shoulder immobilization: (1) scapular depression
      and protraction exercises could potentially be safely performed after rotator
      cuff repair to facilitate scapulothoracic rehabilitation, (2) all exercises
      studied could potentially be safe after superior labral anteroposterior shoulder
      repair, and (3) all exercises studied should be avoided after subscapularis
      repair. Further investigation in symptomatic individuals may facilitate
      refinement of these recommendations.

PMID- 16813780
TI  - Parental report of pain and associated limitations in ambulatory children with
      cerebral palsy.
AB  - OBJECTIVE: To document parental reports about pain in children with cerebral
      palsy (CP). DESIGN: A cross-sectional descriptive study. SETTING: Motion analysis
      laboratory. PARTICIPANTS: Seventy-seven ambulatory children with CP (44 boys, 33
      girls; age range, 3-17y) presenting as consecutive assessments. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Parents completed (1) a semistructured
      interview, (2) the Pediatric Outcome Data Collection Instrument (PODCI), (3) the
      Child Behavior Checklist (CBCL), (4) the Behavior Rating Inventory of Executive
      Functioning (BRIEF), and (5) Gillette Functional Assessment Questionnaire. Two
      dichotomous PODCI pain and comfort questions were estimates of pain frequency and
      impact. RESULTS: Sixty-one percent reported "pain over the last week," and 33%
      reported "pain interfered with normal activities." Pain did not differ by
      topographic classification. Girls had more pain. "Pain that interfered with
      normal activities" was associated with limitations in activities of daily living
      and physical education. Social problems and attention problems on the CBCL and
      the initiate scale on the BRIEF were associated with pain that interfered with
      activity. CONCLUSIONS: Pain in children with CP is frequent and associated with
      behavioral and social consequences. Sex is a risk factor; girls experience more
      pain. Intervention strategies that successfully support transition into adulthood
      are needed.

PMID- 16813781
TI  - Exercise, functional limitations, and quality of life: A longitudinal study of
      persons with multiple sclerosis.
AB  - OBJECTIVE: To explore the trajectories of functional limitations, health
      behaviors (exercise), and quality of life (QOL) and their interrelations over a 5
      year time period in a sample of persons with multiple sclerosis (MS). DESIGN:
      Descriptive longitudinal survey study. SETTING: Southwestern United States.
      PARTICIPANTS: Convenience sample of 611 people with MS (mean age at time 1,
      49.4y). Ninety percent of the participants remained enrolled in the study.
      Response rates at each annual data collection ranged from 85% to 90% of eligible
      participants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A series of
      self-report instruments to measure functional limitations, exercise behaviors,
      and QOL were completed annually over a 5-year period. RESULTS: Using multivariate
      latent curve modeling techniques, rates of change in functional limitations
      correlated negatively with rates of exercise behaviors and QOL ratings. The level
      of exercise behaviors at time 1 and rate of change in functional limitations were
      negatively related-suggesting that higher exercise levels at time 1 were related
      to slower accumulation of functional limitations over time. CONCLUSIONS: Data
      analysis methods that allow examination of both the individual and group level of
      change are particularly appropriate when examining trajectories of change in
      persons with MS because of the highly individualized progression and presentation
      of the disease. Findings of this descriptive longitudinal study support the
      potential positive impact of exercise on the long-term progression of functional
      limitation and QOL for persons with MS.

PMID- 16813782
TI  - The relation between walking capacity and clinical correlates in survivors of
      chronic spinal poliomyelitis.
AB  - OBJECTIVES: To examine (1) common clinical measures that may influence walking
      performance in the six-minute walk test (6MWT) in people with chronic
      poliomyelitis and (2) the test-retest reliability of the 6MWT distance, lower
      extremity muscle strength, balance, and balance confidence on separate trials.
      DESIGN: A prospective quasi-experimental study. SETTING: University-based
      postpolio clinic. PARTICIPANTS: Nineteen survivors of poliomyelitis (mean age,
      62.2+/-1.9y; time since polio onset, 54.4+/-8.79y). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: 6MWT distance, rate-pressure product (RPP),
      Physiological Cost Index (PCI), ratings of perceived exertion (RPE), pain,
      fatigue, strength, standing balance, balance confidence, limb-length discrepancy,
      and lung function. RESULTS: The 6MWT distance correlated with PCI, pretest pain,
      lower-extremity muscle strength, balance, balance confidence, corrected leg
      length discrepancy, and lung function but not with RPP, RPE, posttest pain, or
      pretest and posttest fatigue. The PCI correlated with balance confidence and lung
      function. About 68% of the variance in 6MWT distance was accounted for by balance
      and pretest pain. The P value was set at .05. CONCLUSIONS: With stringent
      standardization of the 6MWT applied to survivors of poliomyelitis (a
      neuromuscular condition with a musculoskeletal component), reproducibility was
      high; hence, test validity and interpretation were enhanced. The 6MWT distance
      was useful in elucidating the relation between impairment and a functional
      activity-namely, walking-in survivors of poliomyelitis.

PMID- 16813783
TI  - Self-reported psychosocial health among adults with traumatic brain injury.
AB  - OBJECTIVE: To measure the subjective psychosocial health of a population-based
      sample of adults with traumatic brain injury (TBI). DESIGN: Retrospective, cohort
      study involving a 1-year postinjury interview. SETTING: Sixty-two acute care,
      nonfederal hospitals in South Carolina. PARTICIPANTS: Persons (> or =15y)
      hospitalized with TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The
      psychosocial health scales of the Medical Outcomes Study 36-Item Short-Form
      Health Survey. RESULTS: Of the 7612 participants, 29% reported poor psychosocial
      health. Factors associated with poor psychosocial well-being included younger
      age, female sex, Medicaid coverage, no health insurance, inadequate or moderate
      social support, comorbidities (eg, a preinjury substance abuse problem),
      cognitive complaints, and some or a lot of limitation with activities of daily
      living. Only 36% of participants who reported poor psychosocial health reported
      receiving any mental health services. CONCLUSIONS: A substantial proportion of
      persons hospitalized with TBI reported poor psychosocial health at 1 year
      postinjury. To optimize recovery, clinicians need to ensure that patients'
      psychosocial health needs are addressed during the postacute period.

PMID- 16813784
TI  - Comparison of the action research arm test and the Fugl-Meyer assessment as
      measures of upper-extremity motor weakness after stroke.
AB  - OBJECTIVE: To assess the relative responsiveness of 2 commonly used upper
      extremity motor scales, the Action Research Arm Test (ARAT) and the Fugl-Meyer
      Assessment (FMA), in evaluating recovery of upper-extremity function after an
      acute stroke in patients undergoing inpatient rehabilitation. DESIGN:
      Prospective. SETTING: An acute stroke rehabilitation unit. PARTICIPANTS: One
      hundred four consecutive admissions (43 men, 61 women; mean age +/- standard
      deviation, 72+/-13y) to a rehabilitation unit 16+/-9 days after acute stroke.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The following assessments
      were completed within 72 hours of admission and 24 hours before discharge: ARAT,
      upper-extremity motor domain of the FMA, National Institutes of Health Stroke
      Scale, FIM instrument total score, and FIM activities of daily living (FIM-ADL)
      subscore. RESULTS: The Spearman rank correlation statistic indicated that the 2
      upper-limb motor scales (ARAT, FMA) correlated highly with one another, both on
      admission (rho = .77, P < .001) and on discharge (rho = .87, P < .001). The mean
      change in score from admission to discharge was 10+/-15 for the ARAT and 10+/-13
      for the FMA motor score. The responsiveness to change as measured by the standard
      response mean was .68 for the ARAT and .74 for the FMA motor score. The Spearman
      rank correlation of each upper-limb motor scale with the FIM-ADL at the time of
      admission was as follows: ARAT, rho equal to .32 (P < .001) and FMA motor score,
      rho equal to .54 (P < .001). CONCLUSIONS: Both the FMA motor score and the ARAT
      were equally sensitive to change during inpatient acute rehabilitation and could
      be routinely used to measure recovery of upper-extremity motor function.

PMID- 16813785
TI  - The effect of environment and task on gait parameters after stroke: A randomized
      comparison of measurement conditions.
AB  - OBJECTIVES: To assess the effect of environment and a secondary task on gait
      parameters in community ambulant stroke survivors and to assess the contribution
      of clinical symptoms to gait performance. DESIGN: A 2x3 randomized factorial
      design with 2 main factors: task (no task, motor task, cognitive task) and
      environment (clinic, suburban street, shopping mall). SETTING: Subjects were
      assessed in 1 of 3 settings: 2 in the community (a suburban street and shopping
      mall) and 1 clinical environment. PARTICIPANTS: Twenty-seven people with stroke
      (mean age, 61+/-11.6y; mean time since stroke onset, 45.8+/-34.2mo), living at
      home, were recruited from community stroke groups and from a local rehabilitation
      unit. Selection criteria included the following: ability to give informed
      consent, unilateral first ever or recurrent stroke at least 6 months previously,
      walking independently in the community, a gait speed between 24 and 50 m/min,
      Mini-Mental State Examination score of 24 or higher, and no severe comorbidity.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait speed (in m/min),
      cadence, and step length were assessed by using an accelerometer with adjustable
      thresholds. Clinical measures hypothesized to influence gait parameters in
      community environments were also assessed including fatigue, anxiety and
      depression, and attentional deficit. RESULTS: Twenty-seven people with a mean
      baseline gait speed of 42.2+/-5.9 m/min were randomly allocated to 1 of 9
      conditions in which the setting and distraction were manipulated. Analysis of
      variance showed a significant main effect for environment (P = .046) but not for
      task (P = .37). The interaction between task and environment was not significant
      (P = .73). Adjusting for baseline gait speed, people walked on average 8.8m/min
      faster in the clinic (95% confidence interval, 0.3-17.3m/min) than in the mall.
      Scores for fatigue, anxiety and depression, and attentional deficit were higher
      than normative values but did not influence gait performance. CONCLUSIONS: This
      study suggests that people with chronic stroke cope well with the challenges of
      varied environments and can maintain their gait speed while performing a
      secondary task. Despite moderate levels of gait impairment, gait automaticity may
      be restored over time to a functional level.

PMID- 16813786
TI  - Knee muscle strength, gait performance, and perceived participation after stroke.
AB  - OBJECTIVE: To assess the relation between knee muscle strength, gait performance,
      and perceived participation in subjects with chronic mild to moderate poststroke
      hemiparesis. DESIGN: Descriptive analysis of convenience sample. SETTING:
      University hospital. PARTICIPANTS: Fifty men and women (mean age, 58+/-6.4y) 6 to
      46 months poststroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Isokinetic concentric knee extension and flexion strength was measured at 60
      degrees /s. Gait performance was assessed by Timed Up & Go, comfortable and fast
      gait speed, stair climbing ascend and descend, and 6-minute walk test. Perceived
      participation was assessed with the Stroke Impact Scale. RESULTS: There was a
      significant correlation (P < .01) between knee muscle strength and gait
      performance for the paretic but not for the nonparetic lower limb. Strength for
      the paretic limb explained 34% to 50% of the variance in gait performance; the
      addition of strength for the nonparetic limb explained at most a further 11% of
      the variance in gait performance. There was a significant correlation (P < .01)
      between gait performance and perceived participation; gait performance explained
      28% to 40% of the variance in perceived participation. CONCLUSIONS: Knee muscle
      strength is a moderate to strong predictor of walking ability in individuals with
      chronic mild to moderate poststroke hemiparesis. Walking ability influences
      perceived participation, but the strengths of the relations indicate that other
      factors are also important.

PMID- 16813787
TI  - Influence of posture and muscle length on stretch reflex activity in poststroke
      patients with spasticity.
AB  - OBJECTIVE: To investigate the influence of different positions on stretch reflex
      activity of knee flexors and extensors measured by electromyography in poststroke
      patients with spasticity and its expression in the Ashworth Scale. DESIGN:
      Crossover trial with randomized order of positioning. SETTING: Outpatient
      rehabilitation center in the Netherlands. PARTICIPANTS: Poststroke patients (N =
      19) with lower-limb spasticity. INTERVENTION: Changing position: sitting versus
      supine. MAIN OUTCOME MEASURES: Root mean square (RMS) values of muscle activity
      and goniometric parameters, obtained during the pendulum test and passive knee
      flexion and extension, and Ashworth scores. RESULTS: RMS values of bursts of
      rectus femoris activity were significantly higher in the supine compared with the
      sitting position (P = .006). The first burst of vastus lateralis activity during
      the pendulum test (P = .049) and semitendinous activity during passive stretch (P
      = .017) were both significantly higher in the supine versus the sitting position.
      For both the pendulum test and passive movement test, the duration and amplitude
      of the cyclic movement of the lower leg changed significantly as well. In the
      supine position, we found significantly higher Ashworth scores for the extensors
      (P = .001) and lower scores for the flexors (P = .002). CONCLUSIONS: The outcome
      of clinical and neurophysiologic assessment of spasticity is influenced
      considerably by subject positioning.

PMID- 16813788
TI  - Does having a computerized prosthetic knee influence cognitive performance during
      amputee walking?
AB  - OBJECTIVE: To compare objective cognitive performance and perception of cognitive
      burden during walking tasks using 2 different prosthetic knees: a computerized
      hydraulic knee (Otto Bock C-leg) and a noncomputerized hydraulic knee (Ossur
      Mauch SNS). DESIGN: Two-group crossover trial, with participants randomly
      assigned to order of prosthesis. Participants completed assessments under 2
      conditions, a self-selected speed walk and a controlled speed walk, on 2 separate
      occasions (precrossover, postcrossover). SETTING: Veterans Health Administration
      hospital. PARTICIPANTS: Eight transfemoral amputees. INTERVENTION: Computerized
      versus noncomputerized prosthetic knee. MAIN OUTCOME MEASURES: Objective
      cognitive performance measures included verbal fluency (Controlled Oral Word
      Association Test, Category Test), attention and working memory (serial
      subtraction), and walking speed during cognitive tasks. Measures of perceived
      cognitive burden included subjective attentional requirements of walking and
      cognitive tasks and subjective general cognitive burden of prosthesis. RESULTS:
      There were no significant differences in objective cognitive performance on any
      task between prostheses, nor did walking speed vary by prosthesis during the free
      speed walk. Participants reported that walking required less attention while
      wearing the C-leg and that the C-leg was less of a cognitive burden than the
      noncomputerized prosthesis. CONCLUSIONS: In nondemanding walking conditions with
      experienced amputees, participants reported that the more costly C-leg required
      less cognitive attention than the noncomputerized knee. However, this subjective
      experience did not translate to improved performance on neuropsychologic
      screening instruments or on walking speed. Noncomputerized prostheses may be
      adequate for a majority of amputees, and further research is needed to identify
      particular groups of amputees (ie, new amputees, amputees with complex physical
      or cognitive demands) who may benefit from computerized prostheses.

PMID- 16813789
TI  - Functional status and factors influencing the rehabilitation outcome of people
      affected by above-knee amputation and hemiparesis.
AB  - OBJECTIVES: To evaluate the functional status of people with transfemoral
      amputation and hemiparesis and to identify the factors that influence
      rehabilitation outcome after inpatient treatment. DESIGN: Retrospective study.
      SETTING: Rehabilitation hospital. PARTICIPANTS: Forty-five patients (30 men, 15
      women; mean age, 69+/-9y) with intact mental status affected by unilateral
      transfemoral amputation for vascular disease and mild or moderate hemiparesis.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Barthel Index, Barthel
      Index effectiveness, and Locomotor Capabilities Index (LCI) scores were measured.
      The following factors were studied: side and cause of amputation, side and
      severity of hemiparesis, sequence and laterality of dual impairment, time
      interval between impairments, and hospital length of stay. RESULTS: At discharge,
      mean Barthel Index and LCI scores +/-1 standard deviation were 79+/-12 and 15+/
      5.6, respectively; Barthel Index effectiveness was 55+/-23.8. Only 2 patients
      ambulated without walking aids. Barthel Index effectiveness was better in
      patients with mild hemiparesis than in patients with more severe impairment.
      Ipsilateral localization of dual impairment increased the probability of higher
      LCI scores. CONCLUSIONS: Selected patients with dual impairment can recover the
      ability to walk. Severity of hemiparesis and laterality were the 2 clinical
      factors that had the greatest influence on functional measures.

PMID- 16813790
TI  - Use of intrathecal baclofen in a child with spastic paraparesis related to human
      immunodeficiency virus infection: A case report.
AB  - This case report describes a 2-year treatment course of a 6-year-old with spastic
      paraparesis due to human immunodeficiency virus (HIV) encephalopathy. She
      continued to develop worsening musculoskeletal problems and a decline in mobility
      despite aggressive antispasticity interventions. In addition to meeting the usual
      clinical criteria for treatment with continuous intrathecal baclofen (ITB), she
      was believed to be an appropriate candidate for ITB because of adequate treatment
      of her HIV infection and associated overall low risk of mortality. For over 12
      months, she has been successfully treated with ITB and has not developed any
      complications related to her HIV infection. To my knowledge, this is the first
      reported successful treatment of spasticity with ITB in a patient with stable HIV
      infection.

PMID- 16813791
TI  - Influence of rehabilitation site on hip fracture recovery in community-dwelling
      subjects at 6-month follow-up.
AB  - OBJECTIVE: To evaluate whether postacute rehabilitation after hip fracture
      influences recovery of prefracture function as detected by the FIM instrument
      motor scale. DESIGN: Inception cohort. SETTING: University-affiliated tertiary
      care hospital; inpatient rehabilitation facilities (IRFs) or skilled nursing
      facilities (SNFs). PARTICIPANTS: People with acute proximal femur fracture
      treated between March 1, 2002, and June 30, 2003. INTERVENTION: Post-hip fracture
      rehabilitation delivered at an IRF or SNF. MAIN OUTCOME MEASURE: FIM motor score
      estimated prefracture and obtained at 2 weeks and 24 weeks after hospital
      discharge. RESULTS: Fifty-eight patients were treated at an IRF, whereas 39 were
      treated at an SNF. Controlling for baseline covariates, a mixed model showed a
      significant group by time interaction (F(3,57.1)=14.27, P < .001). Contrasts
      indicated that IRF subjects had greater initial improvement. Multiple logistic
      regression examining factors associated with recovery of FIM motor score to 95%
      or more of prefracture FIM motor score by 24 weeks found that IRF setting only
      was associated with recovery of baseline function with odds ratio of 5.44 (95%
      confidence interval, 2.02-14.65). CONCLUSIONS: Even when controlling for
      important baseline covariates, community-dwelling hip fracture subjects treated
      in an IRF are more likely to attain 95% or more of prefracture functional status
      by 24 weeks postdischarge than subjects treated in an SNF.

PMID- 16813792
TI  - A novel thoracic weight-bearing long-leg orthosis that permits ambulation after
      massive pelvic tumor resection.
AB  - Osteosarcomas require aggressive medical and surgical treatments that frequently
      result in impaired musculoskeletal function. Amputation was formerly a treatment
      of choice for patients with sarcomas in an extremity. Although there has been
      controversy over the relative benefits of amputation and limb sparing, it is
      undeniable that limb sparing is becoming more common and that it frequently
      leaves a person with a limb whose function is limited. This is particularly true
      in the lower extremities, where pelvic and proximal femoral resections may lead
      to severe weight-bearing and mobility limitations. We report a novel thoracic
      weight-bearing long-leg orthosis that permitted a person who otherwise would not
      have been able to bear weight on a lower extremity after resection of a large
      iliac osteosarcoma to walk with a 4-point gait and forearm crutches.

PMID- 16813793
TI  - A new type of chopsticks for patients with impaired hand function.
AB  - OBJECTIVES: To present a method for adapting chopsticks to persons with hand
      impairments and to compare the efficiency of the adapted chopsticks with spoons
      among adults with cervical spinal cord injury (SCI). DESIGN: Equipment
      development and pilot evaluation. SETTING: Rehabilitation center. PARTICIPANTS:
      Two adults with complete C8-level SCI and 9 adults with incomplete SCI from the
      C6 to C8 level. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Instructions for adapting chopsticks and the time to pick up and manipulate 4
      types of food (noodle strips, cubed carrots, unshelled peanuts, tofu cube) by
      using adapted chopsticks as compared with spoons. RESULTS: The mean time for
      manipulating tofu was comparable between the adapted chopsticks and spoon, but
      the adapted chopsticks were sufficiently faster than spoons for noodle strips,
      carrots, and unshelled peanuts. CONCLUSIONS: Adapted chopsticks convert gross
      grasp into 2-point pinch. They are inexpensive, easily constructed, and may
      benefit patients with lower cervical SCI and residual gross grasp.

PMID- 16813794
TI  - Acetic acid-guided biopsies after magnifying endoscopy compared with random
      biopsies in the detection of Barrett's esophagus: a prospective randomized trial
      with crossover design.
AB  - BACKGROUND: In contrast to standard video endoscopy, magnifying endoscopy after
      local acetic acid application enables recognition of mucosal surface
      architecture. OBJECTIVE: To investigate the diagnostic yield of magnifying
      endoscopy with acetic acid-targeted biopsies compared to random, 4-quadrant
      biopsies. DESIGN: Prospective randomized trial (ratio 1:1) with crossover design.
      SETTING: Two referral hospitals in Germany. PATIENTS: Thirty-one patients with
      Barrett's esophagus or visible columnar-lined lower esophagus. INTERVENTIONS:
      Patients were randomized to undergo either standard video endoscopy with 4
      quadrant biopsies or magnifying endoscopy in conjunction with acetic acid
      application. All patients were re-examined 14 days after the initial endoscopy
      with the corresponding procedure. MAIN OUTCOME MEASUREMENTS: Primary outcome
      analysis (per protocol and per biopsy) was the histological proof of Barrett's
      epithelium. Secondary outcome analysis was the correlation between the surface
      architecture and the presence of Barrett's epithelium and the needed number of
      biopsies to confirm Barrett's epithelium for the 2 different procedures. RESULTS:
      Magnifying endoscopy enabled the prediction of Barrett's epithelium with a
      sensitivity of 100% and a specificity of 66%, respectively (accuracy 83.8%).
      Acetic acid-guided biopsies obtained a significantly higher percentage of tissues
      containing SCE (78%; 188/241) compared to random biopsies (57%; 159/280).
      LIMITATIONS: No data on the diagnosis of Barrett's dysplasia. CONCLUSION:
      Magnifying endoscopy with acetic acid-guided biopsies is superior to standard
      video endoscopy with random biopsies, and the number of biopsies needed to
      confirm Barrett's epithelium is half as much when compared to random biopsies.

PMID- 16813795
TI  - Esophageal chromoendoscopy in Barrett's esophagus: "cons".

PMID- 16813796
TI  - Acetic-acid chromoendoscopy for Barrett's esophagus: the "pros".

PMID- 16813797
TI  - Is genomic evaluation feasible in endoscopic studies of Barrett's esophagus? A
      pilot study.
AB  - BACKGROUND: The global gene expression in Barrett's esophagus (BE) in comparison
      to adjacent or histologically similar tissues has not been extensively studied.
      OBJECTIVE: To test the feasibility of conducting gene arrays in endoscopically
      obtained mucosal specimens. DESIGN: Cross-sectional feasibility study. SETTING:
      The Houston Department of Veterans Affairs Medical Center. PATIENTS: We collected
      endoscopic biopsies from BE, normal esophagus, antrum, duodenum, and sigmoid
      colon from 5 patients with BE. RNA was extracted and subjected to cDNA
      microarrays and gene expression was compared between BE and control tissues.
      Reverse transcription-PCR was conducted to confirm some of the findings. MAIN
      OUTCOME MEASUREMENTS: Gene expression profiles in BE tissues and 4 control sites:
      squamous esophagus, antrum, duodenum, sigmoid colon. RESULTS: On average, 2
      biopsies by disposable jumbo biopsy forceps provided approximately 5 microg
      required for microarrays. From the original number of 22,283 gene probes, 13,805
      genes had a quality score of P < .05 and were subjected to further comparison. BE
      gene expression clustered most closely with that of antrum and least closely with
      squamous esophagus. Of the 587 genes that had significantly different expression
      between BE and duodenum, 246 were upregulated and 341 were downregulated in BE.
      The expression of genes involved in apoptosis, negative regulation of apoptosis,
      and inflammatory response was significantly lower in BE compared to squamous
      esophagus. None of the gene groups were significantly overexpressed in BE
      compared to squamous esophagus or antrum. The reverse transcription-PCR confirmed
      the results of microarrays. LIMITATIONS: Small sample size. CONCLUSIONS:
      Microarray-based studies are feasible in endoscopically obtained tissues.
      Differences in gene expression could identify potential markers and shed light on
      the pathogenesis of BE.

PMID- 16813798
TI  - The genome is now accessible to the endoscopist.

PMID- 16813799
TI  - Yield of tissue sampling for subepithelial lesions evaluated by EUS: a comparison
      between forceps biopsies and endoscopic submucosal resection.
AB  - BACKGROUND: In most circumstances, subepithelial tumors lack distinct endoscopic
      and ultrasonographic features. Consequently, definitive diagnosis usually
      requires tissue acquisition and pathologic confirmation. Establishing a tissue
      diagnosis is difficult because the yield of forceps biopsies is low. However,
      prospective data evaluating tissue sampling techniques for subepithelial lesions
      are currently lacking. OBJECTIVE: Our purpose was to prospectively determine the
      diagnostic yield of endoscopic submucosal-mucosal resection (ESMR) compared with
      forceps biopsy for lesions limited to the submucosa (third endosonographic layer)
      of the GI tract. DESIGN: A prospective head-to-head comparison was performed.
      SETTING: The study was performed in a tertiary care hospital. PATIENTS: Study
      patients were 23 adults with subepithelial lesions limited to the submucosa.
      INTERVENTION: All submucosal lesions underwent forceps biopsy followed by
      endoscopic submucosal resection. Biopsy specimens were obtained with large
      capacity "jumbo" forceps. A total of 4 double passes (8 biopsy specimens) were
      collected from each lesion with use of the bite-on-bite technique. Endoscopic
      resection was then performed with an electrosurgical snare or cap-fitted
      endoscopic mucosal resection device. MAIN OUTCOME MEASUREMENT: The main outcome
      measurement was the diagnostic yield of biopsy forceps compared with endoscopic
      submucosal resection. RESULTS: Twenty-three patients with lesions limited to the
      submucosa were identified by endoscopic ultrasonography. All lesions underwent
      forceps biopsy followed by ESMR. The diagnostic yield of the jumbo forceps biopsy
      was 4 of 23 (17%), whereas the diagnostic yield of ESMR was 20 of 23 (87%) (P =
      .0001, McNemar test). CONCLUSION: In the evaluation of subepithelial lesions
      limited to the submucosa, ESMR has a significantly higher diagnostic yield than
      jumbo forceps biopsy with use of the bite-on-bite technique.

PMID- 16813800
TI  - EUS characteristics of celiac ganglia with cytologic and histologic confirmation.
AB  - BACKGROUND: Celiac ganglia have not been previously identified by EUS. OBJECTIVE:
      To assess whether celiac ganglia can be detected by EUS and to define their
      characteristics. DESIGN: Retrospective review followed by prospective study.
      METHODS: Retrospective characterization was performed of all celiac ganglia that
      were incidentally identified by EUS-guided FNA or tru-cut needle biopsy from
      January 2004 to October 2005. We also prospectively assessed if these structures
      could be visualized in consecutive patients undergoing curved linear-array EUS.
      PATIENTS: Seven patients with celiac ganglia diagnosed by EUS-guided FNA (n = 7)
      and/or tru-cut needle biopsy (n = 1) were reviewed. Twenty-two patients were
      prospectively evaluated by curved-linear-array EUS. SETTINGS: Division of
      Gastroenterology and Hepatology, University of Iowa Hospitals and Clinics, Iowa
      City, Iowa, USA. MAIN OUTCOME MEASUREMENTS: EUS features and detection rate of
      celiac ganglia. RESULTS: All retrospectively evaluated celiac ganglia were
      identified anterior to the aorta, slightly to the left, and cephalad to the
      celiac artery take-off, and medial to the left adrenal gland. The mean distance
      from the celiac artery take-off was 10 mm (+/-3 mm); mean size was 13 mm (+/-3
      mm) by 6 mm (+/-2 mm). They appeared as hypoechoic and multilobulated structures
      with hyperechoic strands. Celiac ganglia with sonographic features as described
      above were identified in 16 of 22 prospectively evaluated patients (73%).
      LIMITATIONS: Small number of patients; no tissue confirmation of prospectively
      evaluated patients. CONCLUSIONS: Celiac ganglia can be identified with curved
      linear-array EUS in the majority of patients. Their typical EUS appearance allows
      distinction from celiac lymph nodes.

PMID- 16813801
TI  - Magnifying pharmacoendoscopy: response of microvessels to epinephrine stimulation
      in differentiated early gastric cancers.
AB  - BACKGROUND: Magnifying endoscopy is a promising modality for fine observation of
      minute surface structures and microvessel architecture in gastric lesions.
      OBJECTIVE: To observe the response of microvessels to epinephrine stimulation in
      early gastric cancer tissues and to assess the usefulness of magnifying
      pharmacoendoscopy for histologic diagnosis. DESIGN: This was a prospective pilot
      study. SETTING: This study was conducted at an academic hospital. PATIENTS:
      Twenty-nine patients with differentiated early gastric cancer were enrolled.
      INTERVENTIONS: Microvessels in both the cancerous lesion and its adjacent non
      neoplastic gastric mucosa were observed by magnifying endoscopy before and after
      focal spray with epinephrine solution (0.05 mg/mL). MAIN OUTCOME MEASUREMENTS AND
      RESULTS: After epinephrine stimulation, noncancerous gastric mucosa surrounding
      the cancerous lesion showed a change in color from red to white; no microvessels
      were evident. On the other hand, all the cancerous lesions examined clearly
      showed enhancement of tumor microvessels. The rate of detection of tumor
      microvessels by magnifying pharmacoendoscopy (100%) was significantly higher than
      that by magnifying endoscopy alone (41.3%). LIMITATIONS: This was small pilot
      study. CONCLUSIONS: Magnifying pharmacoendoscopy with epinephrine is a powerful
      tool for assessing tumor vascularity and may contribute to the histologic
      diagnosis of differentiated early gastric cancers before endoscopic treatment.

PMID- 16813802
TI  - A survey of physician practices on prophylactic pancreatic stents.
AB  - BACKGROUND: Several prospective studies confirm that prophylactic stent placement
      in the pancreatic duct (PD) during high-risk ERCP procedures decreases the risk
      of post-ERCP pancreatitis. Inconsistencies exist regarding the indications for
      prophylactic PD stent placement, the type of stent used, and stent follow-up.
      OBJECTIVE: To assess the current practice patterns of expert biliary endoscopists
      regarding prophylactic pancreatic duct stents. DESIGN: An anonymous survey was
      mailed to 54 expert biliary endoscopists, assessing volume of procedures, stent
      indications, method of placement, and follow-up. RESULTS: A total of 91% (49/54)
      of surveys were returned and analyzed. Prophylactic PD stents were used by 96% of
      respondents. Stent use was universal during ampullectomy and pancreatic
      sphincterotomy. Most also used stents for minor papillotomy (93%) and sphincter
      of Oddi dysfunction (SOD) confirmed by manometry (82%). Endoscopists disagreed on
      the following: pre-cut sphincterotomy (71%), prior post-ERCP pancreatitis (64%),
      suspected SOD (58-69%), and traumatic sphincterotomy (44%). Endoscopists used
      straight stents (33%), pigtail stents (30%), or a combination (33%). Internal
      flanges were always used by 14%, never used by 54%, and sometimes used by 32%.
      Stent size and length varied widely, as did the time stents were left in place,
      and the retrieval method. CONCLUSIONS: Expert biliary endoscopists agree that
      prophylactic PD stenting is indicated during ERCP in high-risk patients. Wide
      variation exists in patient selection and stent placement technique.

PMID- 16813803
TI  - Interventional EUS-guided cholangiography: evaluation of a technique in
      evolution.
AB  - BACKGROUND: Interventional EUS-guided cholangiography (IEUC) has been
      increasingly used as an alternative to percutaneous transhepatic cholangiography
      (PTC) in cases of biliary obstruction when ERCP is unsuccessful. OBJECTIVE: We
      reviewed our experience and technique used for this procedure. DESIGN: Over a 3
      year period, ending July 2005, patients with a failed ERCP were offered an IEUC.
      SETTING: Tertiary care center offering ERCP and interventional EUS. PATIENTS:
      Twenty-eight patients were candidates for IEUC. Two patients had bleeding masses
      and were referred to interventional radiology, 1 patient had a large mass
      occupying the duodenal lumen, and 2 patients refused IEUC. INTERVENTION: EUS was
      used to access the biliary system after which a guidewire was advanced antegrade
      across the obstruction. Either rendezvous with retrograde or antegrade drainage
      was then accomplished. MAIN OUTCOME MEASUREMENTS: Efficacy and safety of IEUC for
      biliary decompression. RESULTS: IEUC was successfully performed in 23 patients,
      with a transgastric-transhepatic (intrahepatic) approach in 13 cases and
      transenteric-transcholedochal (extrahepatic) approach in 10 cases. Therapeutic
      benefit was achieved in 21 patients: 18 underwent successful stent deployment
      across the stricture, whereas 3 patients required a choledochoenteric fistula
      formation. Complications included 1 case of bile leak, 2 cases of self-limited
      pneumoperitoneum, and 1 case of minor bleeding. LIMITATIONS: Single-center
      experience of 2 operators. CONCLUSIONS: IEUC appears efficacious in patients in
      whom ERCP is unsuccessful and is evolving as an attractive alternative to PTC.
      Intrahepatic access to the biliary system appears safer than the extrahepatic
      approach.

PMID- 16813804
TI  - Recurrent symptomatic common bile duct stones after endoscopic stone extraction
      in elderly patients.
AB  - BACKGROUND: Endoscopic sphincterotomy (EST) and stone extraction are established
      therapeutic procedures for common bile duct (CBD) stones. Little is known about
      the outcomes of EST for CBD stones among elderly patients. OBJECTIVES: To examine
      the rate and the risk factors (CBD dilation and/or angulation, periampullary
      diverticulum, and past open cholecystectomy) for recurrent symptomatic CBD stones
      after EST in the elderly. DESIGN AND PATIENTS: A total of 228 patients who
      underwent EST for CBD stones in the period 1997 to 2004 were included. Follow-up
      data were obtained from medical records and by questioning all the patients. The
      correlation between age and stone recurrence, as well as between age and the
      prevalence of risk factors for recurrence was calculated. In addition, a subgroup
      of 45 elderly patients aged > or =80 years was compared with a control subgroup
      of 51 young patients aged < or =50 years, in terms of stone recurrence and
      associated risk factors. SETTING: Single-center, retrospective study.
      INTERVENTIONS: Endoscopic sphincterotomy. MAIN OUTCOME MEASUREMENTS: Symptomatic
      CBD stone recurrence rate and frequency of risk factors for it. RESULTS: In the
      group of all patients, a correlation was found between the age and stone
      recurrence, as well as between age and the known risk factors for recurrent
      stones. In analyzing the 2 subgroups, CBD stones recurred in 20% of the elderly
      patients compared with 4% of the young patients. Risk factors for recurrent CBD
      stones were more common in the elderly, and so was the presence of multiple risk
      factors in the same patient. CONCLUSIONS: Recurrence of symptomatic CBD stones
      after endoscopic therapy was more frequent in the elderly patients because of an
      increased frequency of risk factors.

PMID- 16813805
TI  - Detection of small-bowel neuroendocrine tumors by video capsule endoscopy.
AB  - OBJECTIVES: Carcinoid tumors are the most common GI neuroendocrine tumors (NET).
      They often originate in the small intestine. The primary tumor is often difficult
      to locate, and resection in an early phase is recommended to prevent
      complications. This study evaluated the value of videocapsule endoscopy (VCE) in
      the detection of small-intestinal primary carcinoid tumor. DESIGN: Prospective
      descriptive study. SETTING: Tertiary referral center. PATIENTS: Twenty
      consecutive patients (13 men, 7 women; 60.5 +/- 9.3 years) with metastatic NET of
      unknown primary tumor. INTERVENTIONS: All patients underwent CT, enteroclysis,
      nuclear imaging, and VCE of the small bowel. RESULTS: CTs and enteroclysis did
      not detect a primary small-intestinal carcinoid tumor. Nuclear imaging
      demonstrated abnormalities in the abdominal area in 13 patients but was unable to
      relate this to an intestinal localization in any patient. VCE revealed a small
      intestinal tumor in 9 patients. Three other patients showed external compression
      and erosions. At surgery, 5 patients had a small-intestinal carcinoid tumor, and,
      in 2 patients, a small-intestinal ischemic segment was present. LIMITATIONS: The
      number of false-positive VCE findings was not clear, because not all patients
      underwent surgery. The absence of abnormalities at VCE in patients with
      abnormalities at nuclear imaging might be related to the presence of carcinoid
      tumor restricted to the mesenterium or to a false-negative VCE. CONCLUSIONS: VCE
      had a high diagnostic yield of 45% for identification of primary small-intestinal
      carcinoid tumors. Although nuclear imaging had a comparable diagnostic yield, it
      could not differentiate between intestinal and mesenterial localization of the
      carcinoid.

PMID- 16813806
TI  - Risk assessment for delayed hemorrhagic complication of colonic polypectomy:
      polyp-related factors and patient-related factors.
AB  - BACKGROUND: Hemorrhage is among the most serious complications of colorectal
      polypectomy and may occur after a longer postprocedure interval. OBJECTIVE: We
      aimed to elucidate the risk factors for delayed postpolypectomy hemorrhage,
      including both polyp characteristics and the general condition of the patients.
      DESIGN: Retrospective cohort study. PATIENTS: A total of 6617 cases of colorectal
      polypectomy was performed in 3138 consecutive patients in Japan. MAIN OUTCOME
      MEASUREMENTS: The risk factors for delayed postpolypectomy hemorrhage were
      assessed among polyp characteristics (form, size, histologic features) and the
      method of resection by unconditional logistic regression. Patient conditions
      (smoking, alcohol, hypertension, diabetes mellitus, hyperlipidemia) were compared
      between case-control pairs matched on polyp-related characteristics by
      conditional logistic regression. RESULTS: Hemorrhage occurred in 38 lesions
      (0.57%) of 37 patients (1.2%): 22 required endoscopic hemostasis and 1 required
      blood transfusion. Although polyp size was associated with the occurrence of
      delayed hemorrhage (10.0 +/- 6.9 mm in hemorrhage cases vs 5.6 +/- 3.8 mm in
      others, P < .0001), other polyp-related factors were not significant.
      Hypertension was a complication in 25 of 37 (68%) cases and in 21 of 74 (28%)
      matched controls, showing an adjusted odds ratio of 5.6 (95% CI 1.8-17.2, P =
      .001). Other patient characteristics were not significant. The interval between
      polypectomy and hemorrhage was significantly longer in patients with hypertension
      (median 6 days, range 2-14 days) than in those without hypertension (2.5 days, 1
      9 days; P = .019). LIMITATIONS: This study does not provide information regarding
      prevention of hemorrhage. CONCLUSIONS: Hypertension is a significant risk factor
      for delayed colorectal postpolypectomy hemorrhage. The interval between
      polypectomy and hemorrhage can be as long as 14 days in the presence of
      hypertension.

PMID- 16813807
TI  - Recommendations for endoscopy in the patient on chronic anticoagulation: apply
      with care!

PMID- 16813808
TI  - Endoscopic full-thickness resection: circumferential cutting method.
AB  - BACKGROUND: Endoscopic full-thickness resection (EFTR) at flexible endoscopy
      might allow less-invasive removal of more deeply penetrating cancers that have
      not spread to the serosal surface and more complete histologic examination of the
      excised tissue. OBJECTIVE: A method for closure of full-thickness defects in the
      stomach wall would be valuable for other endosurgical applications. SETTING: A
      method that uses an end cap and band-ligation without prior injection of saline
      solution to perform EFTR gave good results and was safe in pig studies. There is
      a size limitation of cancers that can be resected en bloc when using this method.
      The depth of resection was also variable. DESIGN AND INTERVENTIONS: EFTR was
      achieved by circumferential cutting with a sphincterotome and a snare. A
      prototype bidirectional cutter was tested. Sutured closure was accomplished by
      using a sheathed needle, a metal tag, and a thread at the tip, passed through a
      2.8-mm accessory channel. Knot-tying devices secured the sutured defect. MAIN
      OUTCOME MEASUREMENTS: EFTR was studied in non-survival (n = 4) and survival (n =
      8) experiments in pigs. RESULTS: Full-thickness specimens were resected from the
      gastric wall (100%, 12/12), and the defects were closed by using sewing and knot
      tying devices (100%, 12/12). LIMITATIONS: A healing ulcer at the suturing site
      was evident at follow-up endoscopy in the survival experiments. Bleeding, which
      was stopped by suturing, occurred in 1 pig (8.3%, 1/12). All pigs survived these
      experiments without complications (100%, 8/8). CONCLUSIONS: Circumferential EFTR
      was feasible and appeared safe in survival experiments. This method might allow
      larger and deeper resection of tumors in the gastric wall.

PMID- 16813809
TI  - Endoscopic full-thickness resection: new minimally invasive therapeutic
      alternative for GI-tract lesions.

PMID- 16813810
TI  - Back to school: training a new generation of clinical investigators.

PMID- 16813811
TI  - Colonoscopy with polypectomy in anticoagulated patients.
AB  - BACKGROUND: According to current practice guidelines for performance of
      colonoscopy in patients requiring long-term anticoagulation, polypectomy is
      considered a high-risk procedure for which anticoagulation must temporarily be
      discontinued. However, these guidelines are based on expert opinion, and the
      bleeding risk after polypectomy in anticoagulated patients is not known.
      OBJECTIVE: Measure the risk of postpolypectomy bleeding in patients who undergo
      colonoscopic polypectomy while anticoagulated. DESIGN: Retrospective review of
      patients who underwent polypectomy without discontinuation of anticoagulation.
      SETTING: Veterans Administration Palo Alto Health Care System. PATIENTS: Forty
      one polypectomies were performed in 21 patients. All patients had been receiving
      long-term anticoagulation with warfarin; the average international normalized
      ratio was 2.3 (range 1.4-4.9; normal 0.9-1.2). To prevent supratherapeutic
      anticoagulation, warfarin was withheld for 36 hours before the procedure while
      the patients were on a liquid diet. The average polyp size was 5 mm (range 3-10
      mm). INTERVENTIONS: All patients underwent polypectomy followed immediately by
      prophylactic application of one or two clips to prevent bleeding. MAIN OUTCOME
      MEASUREMENTS: Rate of postpolypectomy bleeding. RESULTS: There were no episodes
      of postpolypectomy bleeding. The 95% CI for the risk of bleeding was 0% to 8.6%
      when analyzed per polypectomy and 0% to 15% when analyzed per patient.
      LIMITATIONS: Small single-center retrospective study. CONCLUSIONS: Our experience
      suggests that small polyps can be removed with a very low risk of bleeding when
      clips are applied immediately after polypectomy. If these results can be
      confirmed in a larger multicenter study, our protocol may become an alternative
      to withholding anticoagulation in patients at high risk of thrombosis.

PMID- 16813812
TI  - Endoluminal endosurgery: rivet application in flexible endoscopy.
AB  - BACKGROUND: Endoluminal endoscopy could be significantly enhanced by adequate
      approaches to wound closure. Current solutions are basically confined to clip
      applications. OBJECTIVE: A new approach to sewing in flexible endoscopy is
      achieved with an endoluminal rivet system. This system allows the application of
      several ligatures without withdrawing the rivet application device to reload. For
      this purpose, a pilot experimental study of the device was conducted, which
      obtained a tissue approximation and avoided the difficult process of knot tying.
      DESIGN: Pilot experimental study. SETTING: The rivet application was tested
      through a 1.8-mm working channel of the endoscope in laboratory and postmortem
      animal tissues. It consists of a flexible anchor at the front and a lockable
      bracket at the rear. Both edges of a defect of the GI wall can be aligned and
      compressed, thus leading to wound closure. INTERVENTIONS: Test samples were
      evaluated in postmortem gastric tissue by using flexible gastroscopes. The
      feasibility of applying a series of rivets with 1 instrument to close transmural
      lacerations of the stomach was demonstrated. Further tests were performed to
      determine the forces to penetrate the gastric wall. MAIN OUTCOME MEASUREMENTS:
      Tissue closure, rivet degradation. RESULTS: The penetration force can be brought
      down to less than 0.57 N by using a magnesium tip. The sharp tip of the rivet,
      which could potentially lacerate healthy tissue after implantation, is degraded
      in the stomach within the first few hours because of rapid corrosion.
      LIMITATIONS: Lack of in vivo feasibility data. CONCLUSIONS: Endoluminal wound
      closure through common gastroscopes and colonoscopes is possible. Further in vivo
      data are required for the rivet system.

PMID- 16813813
TI  - Nasogastric feeding tube placement in patients with esophageal cancer:
      application of ultrathin transnasal endoscopy.
AB  - BACKGROUND: Patients with esophageal cancer often present with dysphagia and
      malnutrition. Obstructive symptoms may improve after radiotherapy and
      chemotherapy. Nutrition support via a nasogastric tube (NG) or gastrostomy is
      very important during treatment. The newly developed ultrathin endoscope
      (Olympus, GIF-N230, outer diameter: 6 mm) has a smaller diameter than the
      standard endoscope and can be introduced into the esophagus via the nasal cavity.
      This article reports on the use of an ultrathin endoscope for NG placement for
      patients with esophageal cancer who presented with dysphagia and failed
      traditional NG tube placement. METHODS: A consecutive series of 40 patients with
      esophageal cancer were referred to our hospital from November 2001 to October
      2002 for endoscopic placement of NG tubes due to failure of traditional methods
      of NG placement. An ultrathin endoscope was used to advance the guidewire into
      the stomach via the nasal cavity. After withdrawal of the scope, the NG tube was
      inserted over the guidewire under fluoroscopy. OBSERVATIONS: A total of 71
      procedures were performed in 40 patients (37 males, 3 females), age 57 +/- 15
      years (range, 37-91 y). Seventy procedures (99%) were successful in completing NG
      tube placement by using an ultrathin transnasal endoscope. Only one procedure
      failed because the esophageal lumen was completely occluded and the guidewire was
      not able to be passed through the obstructed site. The average duration that the
      NG tube was left in place was 49 +/- 35 days (range, 2-144 days). No procedure
      related complications, such as bleeding or perforation, occurred. CONCLUSIONS:
      Using ultrathin transnasal endoscopy to place an NG tube for esophageal cancer
      patients is effective and safe. It simplifies the procedures and increases the
      success rate.

PMID- 16813814
TI  - Grasping forceps-assisted endoscopic mucosal resection of early gastric cancer
      with a novel 2-channel prelooped hood.
AB  - BACKGROUND: Endoscopic mucosal resection with a cap-fitted panendoscope (EMRC)
      such as a soft prelooped hood is a useful, effective, and safe technique. One
      problem with this method is that the lesion cannot always be maintained in the
      center of the cap because the procedure is performed blindly after aspiration.
      OBJECTIVE: We developed a 2-channel prelooped hood that facilitates EMRC while
      simultaneously allowing both grip of the center in the lesion and irrigation of
      the aspiration site and evaluated the usefulness of this end hood for early
      gastric cancer. DESIGN: Retrospective study. SETTING: Between August 2003 and
      October 2004, patients underwent our novel EMR. PATIENTS: Twelve cases of early
      gastric cancer. INTERVENTIONS: Two side holes were fabricated by drilling in the
      cap portion of a conventional soft prelooped hood, and then the irrigation tube
      and the accessory channel tube were glued to the exterior surface of the holes.
      We placed the fabricated transparent hood at the tip of the endoscope and
      performed grasping forceps-assisted endoscopic aspiration mucosectomy. MAIN
      OUTCOME MEASUREMENTS: Accurate aspiration and the rate of en bloc resection.
      RESULTS: We obtained a satisfactory field of view and accurate aspiration in the
      center of the tumor in all lesions. The rate of en bloc resection was 91.7%
      (11/12). LIMITATIONS: Gastric intramucosal cancer. CONCLUSION: Grasping forceps
      assisted endoscopic mucosal resection with a novel 2-channel prelooped hood is
      safe and useful for mucosal resection of intramucosal cancers less than 20 mm and
      may help center the lesion in the cap before resection.

PMID- 16813815
TI  - Immediate endoscopic closure of colon perforation by using a prototype endoscopic
      suturing device: feasibility and outcome in a porcine model (with video).
AB  - BACKGROUND: Perforation is an uncommon but potentially devastating complication
      of colonoscopy. Surgical closure is the standard of care. Immediate endoluminal
      closure of a perforation would avoid the morbidity and mortality associated with
      general anesthesia, laparotomy, and surgical repair. OBJECTIVES: To evaluate the
      feasibility and safety of full-thickness endoscopic closure of colonic
      perforations with a prototype endoscopic suturing device, the Eagle Claw, in a
      porcine model. DESIGN: Endoscopic animal experimental study of closure of colon
      perforation by using a porcine model. SUBJECTS: Ten pigs were included in the
      study. INTERVENTIONS: The Eagle Claw was used to close small perforations (1.5 to
      2 cm) of the colon created by needle-knife with the animal under general
      anesthesia by using the endoluminal route. All animals received intravenous
      antibiotics and were allowed to eat after 24 hours. MAIN OUTCOME MEASUREMENTS:
      The animals were monitored daily for signs of sepsis and peritonitis. On day 7,
      they were euthanized. The peritoneal cavity was examined for fecal peritonitis,
      and the colon perforation site was checked for wound dehiscence and pericolic
      abscess formation. RESULTS: Endoscopic closure of the colon perforation was
      successful in 7 animals, and they recovered well without any sepsis or
      peritonitis. Necropsy did not reveal fecal peritonitis or pericolonic abscess
      formation at the site of perforation, and the perforation healed well. Closure
      was successful in 1 animal, but necropsy revealed dehiscence of the colon
      perforation site. Endoscopic closure was unsuccessful in 2 animals, and these
      were euthanized immediately. CONCLUSIONS: Closure of acute perforation of the
      colon is feasible with the Eagle Claw endoscopic suturing device in a porcine
      model.

PMID- 16813816
TI  - Transmural migration of a prosthetic mesh after surgery of a paraesophageal
      hiatal hernia.

PMID- 16813817
TI  - Unusual esophageal manifestations of Crohn's disease.

PMID- 16813818
TI  - Endoscopist's worry stone.

PMID- 16813819
TI  - Hepatobiliary sarcoidosis mimicking Klatskin's cholangiocarcinoma.

PMID- 16813820
TI  - Transpapillary biliary biopsy for early stage cholangiocarcinoma of the distal
      common bile duct.

PMID- 16813821
TI  - GI stromal tumor diagnosed by capsule endoscopy in a patient with
      neurofibromatosis type 1.

PMID- 16813822
TI  - A case of Diphyllobothrium latum/nihonkaiense infection identified by capsule
      endoscopy in small intestine.

PMID- 16813823
TI  - Capsule endoscopy revealing small-intestinal lymphangiectasia and GI stromal
      tumor polyps in neurofibromatosis type 1.

PMID- 16813824
TI  - Rare colonic tumor causing intussusception.

PMID- 16813825
TI  - Pseudolipomatosis polyposis.

PMID- 16813826
TI  - Double-balloon enteroscopy in patients with GI bleeding of obscure origin.
AB  - BACKGROUND: Small-bowel bleeding is difficult to treat and diagnose. The recent
      introduction of wireless capsule endoscopy permits examination of the entire
      small intestine, but this method lacks tissue sampling and therapeutic
      capabilities. Recently, Yamamoto et al established a double-balloon insertion
      method for enteroscopy that allows examination of the entire small bowel and
      interventional options. OBJECTIVE: To evaluate double-balloon enteroscopy in
      patients with obscure GI bleeding. SETTING: Single-center prospective study.
      PATIENTS: Thirty-one consecutive patients with obscure GI bleeding (13 females,
      18 males; mean age 56.4 +/- 3.2 years). Criteria for inclusion in the study were
      documented iron deficiency anemia (hemoglobin level <10 g/dL or a decrease of >2
      g/dL over > or =2 months); upper endoscopy not revealing a site/cause of blood
      loss; and similarly uninformative lower endoscopy including examination of the
      terminal ileum. INTERVENTIONS: Endoscopic biopsy or therapy was performed as
      clinically indicated. MAIN OUTCOME MEASUREMENTS: Diagnostic yield for patients
      with obscure GI bleeding and patient follow-up. RESULTS: Double-balloon
      enteroscopy was completed without complications in all patients. Bleeding points
      were identified in 23 patients (74.2%). In 21 (91.3%) of these 23 patients the
      cause of blood loss was identified and treated with no further bleeding at 8.5 +/
      0.6 months of follow-up. LIMITATIONS: Small number of patients. CONCLUSIONS:
      These data suggest that double-balloon enteroscopy is useful for evaluation and
      treatment of patients with GI bleeding of obscure origin.

PMID- 16813827
TI  - Segmental amputation of esophagus with bronchial-wall rupture during removal of a
      stent for benign esophageal stricture.

PMID- 16813828
TI  - GI manifestations of Satoyoshi's syndrome.

PMID- 16813829
TI  - EUS diagnosis of pancreatic lipoma: a case report.

PMID- 16813830
TI  - Successful endoscopic resection of ampullary adenoma with intraductal extension
      and invasive carcinoma (with video).

PMID- 16813831
TI  - Capsule endoscopy: a useful tool in portal hypertensive enteropathy.

PMID- 16813833
TI  - Coupled unfolding and dimerization by the PAH2 domain of the mammalian Sin3A
      corepressor.
AB  - Coregulator recruitment by sequence-specific DNA binding transcription factors
      constitutes an important step in many eukaryotic transcription regulatory
      pathways. The Sin3 corepressor is an evolutionarily conserved protein and a key
      component of a large histone deacetylase-associated corepressor complex. The Sin3
      corepressor contains four imperfect repeats of a domain called PAH (paired
      amphipathic helix) that serve as docking sites for a variety of sequence-specific
      DNA binding factors and coregulators. At least two closely related Sin3 proteins
      designated Sin3A and Sin3B have been described in higher organisms and although
      functional differences between these paralogs are only beginning to be
      appreciated, differences at the structural level are poorly understood. Here we
      analyze the conformational properties of the apo form of the mammalian Sin3A
      (mSin3A) PAH2 domain. At low micromolar concentrations, the domain is
      predominantly monomeric and folded in a conformation similar to those found in
      complexes with the Mad1 and HBP1 repressors. Unexpectedly, at higher
      concentrations, the domain dimerizes with concomitant population of a partially
      unfolded conformer. These findings are in contrast to those reported for the
      mSin3B PAH2 domain and may have implications for the manner in which these
      paralogous domains interact with their targets.

PMID- 16813834
TI  - Rolling adhesion of alphaL I domain mutants decorrelated from binding affinity.
AB  - Activated lymphocyte function-associated antigen-1 (LFA-1, alphaLbeta2 integrin)
      found on leukocytes facilitates firm adhesion to endothelial cell layers by
      binding to intercellular adhesion molecule-1 (ICAM-1), which is up-regulated on
      endothelial cells at sites of inflammation. Recent work has shown that LFA-1 in a
      pre-activation, low-affinity state may also be involved in the initial tethering
      and rolling phase of the adhesion cascade. The inserted (I) domain of LFA-1
      contains the ligand-binding epitope of the molecule, and a conformational change
      in this region during activation increases ligand affinity. We have displayed
      wild-type I domain on the surface of yeast and validated expression using I
      domain specific antibodies and flow cytometry. Surface display of I domain
      supports yeast rolling on ICAM-1-coated surfaces under shear flow. Expression of
      a locked open, high-affinity I domain mutant supports firm adhesion of yeast,
      while yeast displaying intermediate-affinity I domain mutants exhibit a range of
      rolling phenotypes. We find that rolling behavior for these mutants fails to
      correlate with ligand binding affinity. These results indicate that unstressed
      binding affinity is not the only molecular property that determines adhesive
      behavior under shear flow.

PMID- 16813835
TI  - Membrane-transferring sequences of the HIV-1 Gp41 ectodomain assemble into an
      immunogenic complex.
AB  - The membrane-proximal stem region of gp41 has been postulated to host the two
      conserved membrane-transferring domains that promote HIV-1 fusion: the amino
      terminal fusion peptide (FP) and the highly aromatic pre-transmembrane sequence.
      Our results confirm that the hydrophobic FP and membrane-proximal sequences come
      into contact and form structurally defined complexes. These complexes are
      immunogenic and evoke responses in rabbits that compete with the recognition of
      native functional gp41 by the 2F5 monoclonal antibody. We conclude that co
      assembly of the FP and the pre-transmembrane sequences might exert a constraint
      that helps maintain a gp41 stem region pre-fusion structure.

PMID- 16813836
TI  - A proximal arginine R206 participates in switching of the Bradyrhizobium
      japonicum FixL oxygen sensor.
AB  - In oxygen-sensing PAS domains, a conserved polar residue on the proximal side of
      the heme cofactor, usually arginine or histidine, interacts alternately with the
      protein in the "on-state" or the heme edge in the "off-state" but does not
      contact the bound ligand directly. We assessed the contributions of this residue
      in Bradyrhizobium japonicum FixL by determining the effects of an R206A
      substitution on the heme-PAS structure, ligand affinity, and regulatory capacity.
      The crystal structures of the unliganded forms of the R206A and wild-type BjFixL
      heme-PAS domains were similar, except for a more ruffled porphyrin ring in R206A
      BjFixL and a relaxation of the H214 residue and heme propionate 7 due to their
      lost interactions. The oxygen affinity of R206A BjFixL (Kd approximately 350
      microM) was 2.5 times lower than that of BjFixL, and this was due to a higher off
      rate constant for the R206A variant. The enzymatic activities of the unliganded
      "on-state" forms, either deoxy or met-R206A BjFixL, were comparable to each other
      and slightly lower (twofold less) than those of the corresponding BjFixL species.
      The most striking difference between the two proteins was in the enzymatic
      activities of the liganded "off-state" forms. In particular, saturation with a
      regulatory ligand (the Fe(III) form with cyanide) caused a >2000-fold inhibition
      of the BjFixL phosphorylation of BjFixJ, but a 140-fold inhibition of this
      catalytic activity in R206A BjFixL. Thus, in oxygen-sensing PAS domains, the
      interactions of polar residues with the heme edge couple the heme-binding domain
      to a transmitter during signal transduction.

PMID- 16813837
TI  - Structure of a complex of tandem HMG boxes and DNA.
AB  - The high-mobility group protein HMGB1 contains two tandem DNA-binding HMG box
      domains, A and B, linked by a short flexible linker that allows the two domains
      to behave independently in the free protein. There is no structural information
      on how the linked domains and linker behave when bound to DNA, mainly due to the
      lack of any DNA-sequence preference of HMGB1. We report the structure
      determination, by NMR spectroscopy, of a well-defined complex of two tandem HMG
      boxes bound to a 16 bp oligonucleotide. The protein is an engineered version of
      the AB di-domain of HMGB1, in which the A box has been replaced by the HMG box of
      the sequence-specific transcription factor SRY, to give SRY.B. In the SRY.B/DNA
      complex, both HMG boxes bind in the minor groove and contribute to the overall
      DNA bending by intercalation of bulky hydrophobic residues between base-pairs;
      the bends reinforce each other, and the basic linker lies partly in the minor
      groove. As well as being the first structure of an HMG-box di-domain bound to
      DNA, this provides the first structure of the B domain of HMGB1 bound to DNA.

PMID- 16813838
TI  - Effects of a behavioural intervention on quality of life and related variables in
      angioplasty patients: results of the EXhaustion Intervention Trial.
AB  - OBJECTIVES: The EXhaustion Intervention Trial investigated the effect of a
      behavioural intervention programme on exhaustion, health-related quality of life
      (HRQL), depression, anxiety, hostility, and anginal complaints in angioplasty
      patients who felt exhausted after percutaneous coronary intervention (PCI).
      METHODS: Seven hundred ten patients were randomized into an intervention group
      and a usual care control group. The group intervention focused on stressors
      leading to exhaustion and on support of recovery. HRQL (measured by the MacNew
      questionnaire), exhaustion [measured by the Maastricht Questionnaire and the
      Maastricht Interview Vital Exhaustion (MIVE)], anxiety (measured by the State
      Trait Inventory), and depression (measured by the structured clinical interview
      for DSM-IV) were assessed at intake and at 6 and 18 months. Presence of anginal
      complaints was assessed at 18 months. RESULTS: The intervention had a significant
      beneficial effect on all psychological factors except hostility and on the
      presence of anginal complaints. The effect of the intervention on exhaustion, as
      assessed by the MIVE, was modified by a previous history of coronary artery
      disease (CAD). Gender modified the effect of the intervention on exhaustion and
      on anxiety, the strongest effect being observed in women. CONCLUSIONS: The
      behavioural intervention improved HRQL and related psychological factors. Somatic
      comorbidity and a history of CAD limited the effect of the intervention.

PMID- 16813839
TI  - Intervening for exhaustion.

PMID- 16813840
TI  - Risk factors for impaired health status differ in women and men treated with
      percutaneous coronary intervention in the drug-eluting stent era.
AB  - OBJECTIVES: In patients treated with percutaneous coronary intervention (PCI) in
      the drug-eluting stent era, we compared women's and men's health status 6 and 12
      months post-PCI and investigated whether predictors of poor health status at 12
      months are similar for women and men. METHODS: Consecutive patients (n=692; 28%
      women) treated with PCI completed the 36-item Short-Form Health Survey (SF-36) 6
      and 12 months post-PCI. RESULTS: There was a significant improvement in health
      status over time (P<.001), but women experienced a significantly poorer health
      status compared with men (P<.001) at 6 and 12 months, adjusting for differences
      in baseline characteristics and health status at 6 months. Predictors of impaired
      health status were generally different for women and men. In women, the
      predominant predictors were previous coronary artery bypass graft (CABG) surgery,
      renal impairment, and older age; in contrast, in men, older age was associated
      with better functioning. In women, previous CABG was associated with a 4-15 fold
      increased risk of impaired health status. Health status at 6 months was a
      predictor of all SF-36 domains at 12 months in both women and men. CONCLUSIONS:
      Women reported poorer health status compared with men 6 and 12 months post-PCI,
      and predictors of impaired health status generally differed for women and men.
      Further studies examining risk factors for adverse outcomes for women and men
      separately, which will lead to better risk stratification in research and
      clinical practice, are warranted.

PMID- 16813841
TI  - QT interval duration in apparently healthy men is associated with depression
      related personality trait neuroticism.
AB  - OBJECTIVE: High levels of neuroticism and low self-esteem are markers for
      vulnerability to depression, a condition associated with a higher risk of
      arrhythmias. The question as to whether these depression-related personality
      domains are related to cardiac repolarization (duration of QT interval) in
      apparently healthy men has been addressed in this study. METHODS: Participants
      were 658 clinically healthy males who underwent a health screening programme. QT
      interval duration was determined in the resting 12-lead electrocardiogram using
      an automated analysis program. Neuroticism was assessed by the short-scale
      Eysenck Personality Questionnaire and self-esteem by the Rosenberg self-esteem
      scale. RESULTS: Heart-rate corrected QT interval {QTc, formula of Bazett [Bazett
      HC. An analysis of time relations of electrocardiograms. Heart 1920;7:353-370]}
      progressively increased across quartiles of neuroticism ratings. By contrast, no
      differences in QTc were observed across different degrees of self-esteem. A
      multivariate regression analysis showed that neuroticism was a statistically
      significant, independent predictor of QTc duration. CONCLUSION: After adjustment
      for potential confounders, neuroticism scores independently predicted QT interval
      duration in apparently healthy men. These findings highlight the possibility that
      higher arrhythmic risk could be present not only in patients with clinical
      depression but also in depression-prone, otherwise healthy individuals.

PMID- 16813842
TI  - Increased pulse-wave velocity in patients with anxiety: implications for
      autonomic dysfunction.
AB  - Decreased vagal function is associated with vascular dysfunction. In this study,
      we compared vascular indices and correlated heart rate and QT variability
      measures with vascular indices in patients with anxiety disorders and normal
      controls. We compared age- and sex-matched controls (n=23) and patients with
      anxiety (n=25) using the Vascular Profiler (VP-1000; Colin Medical Instruments,
      Japan), approved by the US Food and Drug Administration. Using this machine, we
      obtained ankle and brachial blood pressure (BP) in both arms (brachial), both
      legs (ankle), and carotid artery, and lead I electrocardiogram (ECG) and
      phonocardiogram. Using these signals, pulse-wave velocity (PWV), and arterial
      stiffness index % and preejection period can be calculated. We also obtained ECG
      sampled at 1000 Hz in lead II configuration in supine posture to obtain beat-to
      beat interbeat interval (R-R) and QT interval variability for 256 s. Patients
      with anxiety had significantly higher carotid mean arterial pressure (MAP) %,
      brachial-ankle PWV (BAPWV), arterial stiffness index %, MAP, and diastolic BP of
      the extremities compared to controls. We found significant negative correlations
      (r values from .4 to .65; P<.05 to .007) between R-R interval high-frequency
      (0.15-0.5 Hz) power (which is an indicator of cardiac vagal function), and
      increased BAPWV and systolic BP of the extremities only in patients. We were
      unable to find such correlations in controls. We also found significant positive
      correlations between QT variability index (a probable indicator of cardiac
      sympathetic function) and MAP of the extremities and BAPWV only in the patient
      group. These findings suggest an important association between decreased vagal
      and increased sympathetic function, and decreased arterial compliance and
      possible atherosclerotic changes and increased BP in patients with anxiety.

PMID- 16813843
TI  - Hostility, anger, and sense of coherence as predictors of health-related quality
      of life. Results of an ASCOT substudy.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship of hostility
      and anger expression to sense of coherence (SOC) and their role as predictors of
      health-related quality of life (HQL). It was hypothesised that SOC would mediate
      the impact of hostility and anger on HQL. METHODS: This is a substudy of the
      Anglo-Scandinavian Cardiac Outcomes Trial, which evaluates different treatment
      strategies to prevent cardiovascular disease in hypertensive patients. At
      baseline, SOC was assessed with a short form measure, and hostility-anger with
      the Cynical Distrust scale and with the Anger Expression scales. HQL was assessed
      at 6 months with the RAND-36. The sample comprised of 774 subjects (77.5% men).
      RESULTS: Results showed that strong SOC associates with ability to control
      expression of anger and with low levels of suppressed or openly expressed anger.
      Anger control and SOC were related to good HQL; cynicism, anger-out, and anger-in
      correlated negatively with HQL. Path models revealed that SOC was the strongest
      predictor of HQL while hostility and anger lost their direct impact on HQL.
      CONCLUSIONS: Given the significant associations of hostility and anger with SOC,
      it is concluded that the salutogenic theory of Antonovsky (A. Antonovsky, Health,
      Stress, and Coping: New Perspectives on Mental Health and Physical Well-Being,
      Jossey-Bass Inc, San Francisco, 1979) should be extended to include hostility
      related constructs. The impact of hostility and anger on HQL is, to a great
      extent, mediated through SOC, which implies that in future studies, the role of
      hostility as a risk factor of ill health should be reconsidered from the SOC
      theory perspective.

PMID- 16813844
TI  - Is the impact of depressive complaints on the use of general health care services
      dependent on severity of somatic morbidity?
AB  - OBJECTIVE: The aim of this study was to examine the effects of depressive
      complaints and chronic medical illnesses on prospective somatic health care
      utilization and the possible heterogeneity of the effect of depressive complaints
      across levels of medical illness severity. METHODS: Data from a community-based
      sample of adults (n=9428) were used, of whom a health survey and claims data,
      indicating health care use, were available. Assessments of depressive complaints
      and somatic illnesses were based on self-report. Binomial regression analyses
      were used to study the expected relations. RESULTS: Depressive complaints and
      somatic morbidity were both positively related to general health care
      utilization. Somatic morbidity has an attenuating effect on the impact of
      depressive complaints: If it becomes more severe, the impact of depressive
      complaints on utilization is reduced. Depressive complaints are especially
      related to the use of paramedic services, use of prescription drugs, and
      consultations of medical specialists. CONCLUSION: Depressive complaints predict
      somatic health care utilization, but somatic morbidity attenuates this relation.
      Future research on this subject should include interaction effects of depressive
      complaints and somatic morbidity. Interventions aiming to reduce excess use
      related to mental distress should be primarily targeted on subjects with mental
      distress who have no comorbid somatic morbidity.

PMID- 16813845
TI  - A path model of the effects of spirituality on depressive symptoms and 24-h
      urinary-free cortisol in HIV-positive persons.
AB  - OBJECTIVE: The present investigation examined the associations among
      spirituality, positive reappraisal coping, and benefit finding as they relate to
      depressive symptoms and 24-h urinary-free-cortisol output. METHODS: Following an
      initial screening appointment, 264 human-immunodeficiency-virus-positive men and
      women on highly active antiretroviral therapy provided 24-h urine samples and
      completed a battery of psychosocial measures. RESULTS: Spirituality was
      associated with higher positive reappraisal coping and greater benefit finding.
      Benefit finding and positive reappraisal coping scores were, in turn, both
      related to lower depressive symptoms. Finally, we determined that benefit finding
      was uniquely predictive of decreased 24-h urinary-free cortisol output.
      CONCLUSION: Positive reappraisal coping and benefit finding may co-mediate the
      effect of spirituality on depressive symptoms, and benefit finding may uniquely
      explain the effect of spirituality on 24-h cortisol output.

PMID- 16813846
TI  - The association between burnout and physical illness in the general population-
      results from the Finnish Health 2000 Study.
AB  - OBJECTIVE: The association between burnout and physical diseases has been studied
      very little. The purpose of this study was to examine the relationship between
      burnout and physical illness in a representative nationwide population health
      study. METHODS: As a part of the "Health 2000 Study" in Finland, 3368 employees
      aged 30-64 years were studied. Burnout was assessed with the Maslach Burnout
      Inventory-General Survey. Physical diseases were diagnosed in a comprehensive
      health examination by research physicians. RESULTS: Physical illness was more
      common among subjects with burnout than others (64% vs. 54%, P<.0001), and the
      prevalence of diseases increased with the severity of burnout (P<.0001). Burnout
      was an important correlate of cardiovascular diseases among men (OR=1.35; 95% CI,
      1.13-1.61) and musculoskeletal disorders among women (OR=1.22, 95% CI, 1.07-1.38)
      when adjusted for age, marital status, education, socioeconomic status, physical
      strenuousness of work, smoking, physical activity, alcohol consumption, body mass
      index, and depressive symptoms. The prevalence of musculoskeletal disorders and
      cardiovascular diseases increased with the severity of all three dimensions of
      burnout, that is, exhaustion (P<.0001 and P<.001, respectively), cynicism
      (P=.0001 and P<.001, respectively), and lack of professional efficacy (P<.01 and
      P<.0001, respectively). CONCLUSIONS: Burnout is associated with musculoskeletal
      diseases among women and with cardiovascular diseases among men. These
      associations are not explained by sociodemographic factors, health behavior, or
      depression. Physical illnesses are associated with all three dimensions of
      burnout and not only with the exhaustion dimension. In the future, the causal
      relationships between burnout and physical diseases need to be investigated in
      prospective studies.

PMID- 16813847
TI  - Emotion with tears decreases allergic responses to latex in atopic eczema
      patients with latex allergy.
AB  - OBJECTIVE: Allergic responses are enhanced by stress, whereas they are reduced by
      laughter in atopic eczema patients. Emotion with tears decreases plasma IL-6
      levels in patients with rheumatoid arthritis. Thus, the effect of emotion with
      tears on allergic responses in patients with atopic eczema was studied. METHODS:
      Sixty patients with atopic eczema having latex allergy viewed both the weather
      information video and the heart-warming movie, Kramer vs. Kramer. Just before and
      immediately after viewing each video, allergic responses to latex were measured.
      RESULTS: Viewing the weather information video did not cause emotion with tears
      in any patients, and it failed to modulate allergic responses. In contrast,
      viewing Kramer vs. Kramer caused emotion with tears in 44 of 60 patients, and it
      reduced allergic skin wheal responses to latex and latex-specific IgE production
      in them. CONCLUSION: Emotion with tears reduced allergic responses, and it may be
      useful in the treatment of allergic diseases.

PMID- 16813848
TI  - The Chemical Odor Sensitivity Scale: reliability and validity of a screening
      instrument for idiopathic environmental intolerance.
AB  - OBJECTIVE: The objective of this study was to examine the psychometric qualities
      of a brief screening measure for idiopathic environmental intolerance (IEI), the
      Chemical Odor Sensitivity Scale (COSS). METHODOLOGY: The COSS was administered
      together with other measures of environmental sensitivity, IEI, and symptom
      scales in large samples (students, individuals with IEI, and individuals without
      IEI). RESULTS: The COSS achieved high internal consistency (.88 < or = Cronbach's
      alpha < or = .96) and good factorial, convergent, and discriminant validity
      across diverse samples. In a longitudinal sample, the COSS and other IEI features
      were stable across time. According to receiver operating characteristic analyses,
      the COSS performs adequately in screening individuals likely to meet case
      criteria for IEI. CONCLUSIONS: The favorable psychometric qualities of the COSS
      recommend the scale as a useful tool both for assessing self-reported chemical
      odor sensitivity as a vulnerability marker and for screening for IEI.

PMID- 16813849
TI  - Cognitive and emotional factors in placebo analgesia.
AB  - OBJECTIVE: Information that a painkiller has been administrated induces an
      expectancy of reduced pain, and the expectancy has been shown to reduce pain.
      This is termed placebo analgesia. We hypothesized that an expectancy of reduced
      pain reduces stress. METHODS: The present study (N=84) investigated this
      hypothesis. To further study the effects of stress and emotions on pain, we
      provided information about the pain stimulus to half the subjects. Pain was
      induced by the submaximum tourniquet technique. RESULTS: Expectations and pain
      information both decreased pain to the same degree, but independently, and only
      in males. Lower pain was not related to subjective stress, cortisol, or
      circulating beta-endorphin. All experimenters were women, and the finding of
      placebo analgesia only in males fits well with findings that males report less
      pain to female experimenters. CONCLUSION: Placebo analgesia is not related to
      stress and is influenced by the social context in which pain is recorded.

PMID- 16813850
TI  - Gyneco-psychosomatic counseling in Germany and Switzerland--aims and state of the
      art.
AB  - OBJECTIVE: To investigate actual counseling models for gynecological patients in
      Switzerland and in Germany. METHODS: A questionnaire investigating psychosomatic
      care was sent to all Swiss (N=183) and German (N=1078) departments of gynecology,
      obstetrics, and/or endocrinology. RESULTS: One hundred twenty-eight (27%)
      completed questionnaires from Germany and 57 (31%) from Switzerland were
      available for statistical evaluation. Eighty-seven percent of the answering
      clinics from Switzerland and 93% of those from Germany (ns) considered
      psychosomatic counseling for gynecological and obstetrical patients as very
      important or important. Seventy-two percent of the Swiss and 70% of the German
      departments (ns) offered psychosomatic support. Models of counseling varied
      greatly between types of hospitals and both countries. Less than 15% of the
      medical doctors had a formation for psychosomatic counseling. CONCLUSION: Actual
      possibilities seem to be below the need for psychosomatic care. An adequate
      formation of medical doctors and considering the effects of psychosomatic care in
      the discussion on cost reduction for medical treatment would help to improve
      counseling structures.

PMID- 16813851
TI  - Prevalence of mental disorders in normal-weight and obese individuals with and
      without weight loss treatment in a German urban population.
AB  - OBJECTIVE: The aim of the study was to evaluate the prevalence rates of mental
      disorders in normal-weight individuals and obese individuals with and without
      weight loss treatment. METHODS: A sample of 251 participants in a conventional
      weight loss treatment, 153 pre-bariatric surgery patients, 174 normal-weight
      control participants, and 128 obese control participants not actively losing
      weight at the time of the investigation were examined. RESULTS: Lifetime
      prevalence rates of mental disorders in obese women ranged from 46.7% to 60.1%
      compared with 41.7% in normal-weight women and from 48.0% to 54.4% in obese men
      compared with 29.8% in normal-weight men. Prevalence rates of mental disorders
      did not differ significantly between normal-weight and obese women not currently
      in weight loss treatment; however, the rates were significantly lower compared
      with both obese treatment groups. Compared with normal-weight men, obese men not
      currently in weight loss treatment and obese men participating in conventional
      weight loss treatment showed significantly higher prevalence rates of mental
      disorders. CONCLUSION: Unlike obese male individuals, obese female participants
      not currently in weight loss treatment did not differ from normal-weight
      participants with regard to comorbidity of mental disorders. However, obese
      female participants who were engaged in weight loss treatment exhibited
      significantly higher prevalence rates than normal-weight participants.

PMID- 16813852
TI  - Relationships between maternal and adolescent weight-related behaviors and
      concerns: the role of perception.
AB  - OBJECTIVE: The purpose of this study was to explore the relationship between
      maternal and adolescent weight-related behaviors and concerns in a population
      based sample. METHODS: Participants were 810 adolescents (n=429 girls and n=381
      boys) and their mothers/guardians. Adolescents were part of the Project EAT
      (Eating Among Teens) study, which was a comprehensive study of eating patterns
      and weight concerns among adolescents in Minnesota. Outcome variables included
      child's body dissatisfaction, weight concerns, dieting, and use of healthy and
      unhealthy weight control behaviors. RESULTS: Adolescents reported lower rates of
      maternal dieting than mothers. Maternal self-report of dieting was not
      significantly associated with children's weight-related concerns. Children's
      perceptions of their mothers' behaviors were significantly related to their level
      of weight concerns and use of weight control behaviors. CONCLUSION: Adolescents'
      perceptions of maternal behavior affect their weight-related concerns and
      behaviors. This suggests that mothers who choose to diet should model healthy
      choices in the areas of nutrition and physical activity.

PMID- 16813853
TI  - Three assessment tools for deliberate self-harm and suicide behavior: evaluation
      and psychopathological correlates.
AB  - OBJECTIVE: The aims of this study are to adapt two validated self-report
      questionnaires of deliberate self-harm and suicidal behavior to German, to
      investigate their psychometric properties and agreement with clinician
      administered ratings, and to examine their psychopathological correlates.
      METHODS: The Deliberate Self-Harm Inventory [Gratz KL. Measurement of deliberate
      self-harm: preliminary data on the deliberate self-harm inventory. J Psychopathol
      Behav 2001;23:253-263] and the Self-Harm Behavior Questionnaire [Guttierez PM,
      Osman A, Barrios FX, Kopper BA. Development and initial validation of the self
      harm behavior questionnaire. J Pers Assess 2001;77:475-490] were completed by 361
      patients hospitalized for depressive, anxiety, adjustment, somatoform, and/or
      eating disorders. A clinician-administered rating scale of self-destructive
      behavior was included. Psychopathological variables were assessed by standardized
      questionnaires. RESULTS: The self-report questionnaires demonstrated good
      reliability (alpha=.81-.96, split-half r=.78-.98, test-retest r=.65-.91).
      Reliability of the clinician-administered ratings was acceptable (interrater
      kappa=.46-.77, test-retest kappa=.35-.48). Intraclass correlations (ICC=.68) for
      all three instruments were satisfactory. Rates of self-harm and associations
      between self-harm and suicidal behaviors are reported. The findings support the
      hypotheses of a higher degree of psychiatric symptomatology in patients with self
      harm behavior compared to those without. CONCLUSION: The two questionnaire
      adaptations are reliable and valid self-report scales for the assessment of self
      harm and past suicidal behavior.

PMID- 16813854
TI  - A survey of delirium guidelines in Europe.
AB  - OBJECTIVE: The aim of this study was to investigate the existence and content of
      delirium guidelines of the national psychiatric associations in Europe. METHOD: A
      survey was sent by email to national coordinators of the European Association for
      Consultation-Liaison Psychiatry and Psychosomatics. RESULTS: Responses were
      obtained for 12 of the 14 countries that were approached. Of these 12 countries,
      only two national psychiatric associations reported having national delirium
      guidelines. The Dutch Psychiatric Association was the only national psychiatric
      association that had developed a comprehensive multidisciplinary guideline on the
      diagnosis and treatment of delirium. The German Association of Scientific Medical
      Societies has a comprehensive guideline on the treatment of alcohol withdrawal
      delirium, in which the German Society for Psychiatry, Psychotherapy, and Mental
      Disorders participated. In addition, the delirium guideline of the British
      Geriatrics Society and the guideline for alcohol withdrawal delirium of the
      German Neurological Society were mentioned by respondents. CONCLUSIONS: Although
      the development of evidence-based treatment guidelines is considered an important
      way to improve clinical practice, the national psychiatric associations of only
      two countries have such a guideline for the diagnosis and treatment of delirium.
      The advantages of supranational collaboration in the development of guidelines
      are stressed.

PMID- 16813859
TI  - Ancestry, genetic susceptibility, E-cadherin-160A and prostate cancer risk-is
      there an association?

PMID- 16813860
TI  - Radical prostatectomy-which patients benefit most from surgery?

PMID- 16813861
TI  - Female urology: the changing realm of diagnosis and management.

PMID- 16813862
TI  - Continuing controversy over monitoring men with localized prostate cancer: a
      systematic review of programs in the prostate specific antigen era.
AB  - PURPOSE: There is continuing controversy over the most appropriate treatment for
      screen detected and clinically localized prostate cancer, and increasing interest
      in monitoring such men initially with radical treatment targeted at cancers
      showing signs of progressive potential but while they are still curable. Current
      evidence on monitoring protocols and biomarkers used to predict disease
      progression was systematically reviewed. MATERIALS AND METHODS: The MEDLINE and
      Excerpta Medica (EMBASE) bibliographic databases were searched from 1988 to
      October 2004, supplemented by manual searches of reference lists, focusing on
      studies reporting monitoring of men with localized prostate cancer. RESULTS: A
      total of 48 potentially eligible articles were found but only 5 studies, in which
      there was a total of 451 participants, restricted entry criteria to men with
      clinically localized (T1-T2) prostate cancer. Monitoring protocols varied with
      little consensus, although the majority used prostate specific antigen and
      digital rectal examination, while some added re-biopsy to assess progression.
      Actuarial probabilities of freedom from disease progression at 4 to 5 years of
      followup were 67% to 72%. However, up to 50% of men abandoned monitoring within 2
      years, largely because of anxiety related to increasing prostate specific antigen
      rather than objective evidence of disease progression. There was no robust
      evidence to support prostate specific antigen doubling times or velocity to
      identify men in whom disease may progress. Studies were characterized by small
      sample size, short-term followup, observer bias and uncertain validity around
      variable definitions of progression. CONCLUSIONS: Current evidence suggests that
      some form of monitoring would be a suitable treatment option in men with
      localized prostate cancer but there is little consensus over what markers should
      be used in such a program or how progression should be properly defined. The
      search for a method that safely identifies men with prostate cancer who could
      avoid radical intervention must continue.

PMID- 16813863
TI  - Consumption of historical and current phytotherapeutic agents for urolithiasis: a
      critical review.
AB  - PURPOSE: Recent years have shown a dramatic expansion in the knowledge of
      molecular mechanism of phytotherapeutic agents used to treat urolithiasis. The
      discovery and elucidation of the mechanism of action, in particular the clinical
      role of these herbal remedies, has made an important contribution to treatment
      for urinary stone disease as an alternative or adjunct therapy. Thus, the
      potential clinical application of these folk medicines to urolithiasis is
      discussed. MATERIALS AND METHODS: The literature on phytotherapeutic agents with
      scientifically determined efficiency and historically consumed agents was
      reviewed using MEDLINE after 1940 to the present. RESULTS: Although information
      on the complete mechanism of action of each remedy is lacking, commonly known
      extracts exert antilithogenic properties by altering the ionic composition of
      urine or by expressing diuretic activity. Also, some of them contain saponins
      that can disaggregate suspensions of mucoproteins, which are actually promoters
      of crystallization and some herbal remedies have antimicrobial properties that
      protect the anti-adherent layer of the mucosa, which acts as a protective barrier
      against urinary stone disease. CONCLUSIONS: Although phytotherapeutic extracts
      are popular in folk culture, because of the absence of scientific data on the
      exact clinical role, efficacy and side effects of these herbs the potential
      consumption of this alternative medical therapy as an alternative or adjunct to
      classic therapy remains to be determined. In this respect scientific research
      designed to determine the exact mechanism of action of these drugs would be
      fruitful for willing investigators.

PMID- 16813864
TI  - Arousing properties of the vulvar epithelium.
AB  - PURPOSE: The initiation of genital tactile stimulation is regarded as a precursor
      to sexual arousal and perhaps in women it is the most easily recognized initiator
      of central nervous system arousal. Unfortunately little published material
      details the specific mechanisms preceding arousal, beginning at the epithelial
      level, which are the sensory precursors to arousal. Little is known about its
      cutaneous receptors, nerves and the other histochemical properties of this
      epithelial tissue that contribute to sexual arousal. Sexual sensitivity
      evaluations target female genital somatosensory pathways for cutaneous sensation
      by testing evoked potentials of nerves, hot/cold and vibratory sensory
      discrimination. The anatomical bases of these several sensibilities form a
      subject for future investigation. We reviewed the known influences and mechanisms
      responsible for the arousing properties of the epithelium in the female external
      genitalia as well neural pathways associated with sexual arousal originating from
      the vulvar epithelium. MATERIALS AND METHODS: A comprehensive review was done of
      published, relevant clinical and histological material in human and nonhuman
      vertebrate studies. RESULTS: Tactile stimulation of the vulvar epithelium
      initiates changes suggesting complex integrative mechanisms. Influences of skin
      temperature, hormonal environment, mechanical tissue compliance and inflammation
      as well as the large number of transmitters and neuropeptides involved in
      peripheral pathways serving female sexual arousal speak of a direct sensory role.
      CONCLUSIONS: Genital epithelial cells may actively participate in sensory
      function to initiate sexual arousal by expressing receptors and releasing
      neurotransmitters in response to stimuli, resulting in epithelial-neuronal
      interactions.

PMID- 16813865
TI  - Results of computerized tomography guided percutaneous ablation of renal masses
      with nondiagnostic pre-ablation pathological findings.
AB  - PURPOSE: Ablative therapy for renal masses has been criticized because the entire
      tumor cannot be evaluated pathologically after the procedure. Diagnosis depends
      on imaging findings and the results of percutaneous needle biopsies, which may be
      nondiagnostic in up to 21% of cases. We determined outcomes in patients
      undergoing ablation who had nondiagnostic biopsies at the time of the procedure.
      MATERIALS AND METHODS: A total of 79 patients (88 renal masses) underwent
      percutaneous computerized tomography guided biopsy and ablation of a renal mass
      under conscious sedation. Patients with nondiagnostic biopsies were identified
      and the medical records were reviewed retrospectively. All patients had an
      enhancing renal mass on preoperative computerized tomography or magnetic
      resonance imaging and all underwent postoperative contrast imaging to evaluate
      persistent viable tumor. RESULTS: A total of 19 patients (20 tumors) with
      nondiagnostic percutaneous biopsy (22.7% or 20 of 88) were included in the study.
      No serious complications occurred. Tumors were treated with frequency ablation
      (12) or cryoablation (7). In 17 patients (89.5%) post-procedure imaging confirmed
      the absence of contrast enhancement at a median followup of 27.3 months (range 3
      weeks to 56 months). In 2 cases (10.5%) post-procedure imaging showed a residual
      renal mass or recurrence with enhancement, suggesting that the original
      percutaneous biopsy result was false negative. In 1 patient residual tumor was
      identified on initial post-ablation imaging and the patient underwent
      laparoscopic partial nephrectomy. In another patient recurrence was diagnosed 30
      months after ablation and the patient underwent laparoscopic radical nephrectomy.
      Although there was a nondiagnostic percutaneous biopsy in each case, pathological
      findings in the subsequent surgical specimen confirmed renal cell carcinoma.
      CONCLUSIONS: Nondiagnostic percutaneous biopsy at renal tumor ablation does not
      obviate the need for standard post-procedure imaging followup. Of patients with
      nondiagnostic biopsies in this series 10.5% still harbored viable renal cell
      carcinoma after percutaneous ablation.

PMID- 16813868
TI  - Venacavoscopy during nephrectomy for renal cell carcinoma with inferior vena
      caval thrombus.
AB  - PURPOSE: Renal cell carcinoma with inferior vena caval thrombus remains a complex
      challenge for the urologist. Aggressive surgery to remove all tumor can result in
      long-term survival. Liver transplant techniques, assistance from cardiac surgeons
      and bypass techniques can yield optimal vascular control but there is still a
      blind element inside the inferior vena cava when the thrombus is evacuated. We
      present data on a technique using a flexible cystoscope to evaluate the lumen of
      the intrahepatic and suprahepatic inferior vena cava after nephrectomy and tumor
      thrombectomy. MATERIALS AND METHODS: Seven patients underwent radical nephrectomy
      and tumor thrombectomy for renal cell carcinoma with inferior vena caval
      thrombus. During surgery and after removal of the tumor thrombus a flexible
      cystoscope was inserted into the venacavotomy for direct inspection of the
      inferior vena caval lumen. Any residual tumor was manipulated out of the lumen
      and removed. Patient records were reviewed for data on the time of this
      procedure, estimated blood loss, residual tumor, postoperative complications and
      survival. RESULTS: Venacavoscopy required an average additional 5.6 minutes and
      residual tumor was found in 3 of 7 patients. Average estimated blood loss was
      1,170 cc and it was not affected by venacavoscopy. One patient experienced
      acalculous cholecystitis, possibly as a result of this procedure. Mean followup
      was 17.6 months with 5 of 7 patients alive. CONCLUSIONS: Venacavoscopy is a safe,
      reliable method of intraoperative inspection of the inferior vena cava that uses
      equipment and techniques familiar to every urologist. This can help prevent
      incomplete thrombectomy and disastrous pulmonary embolus.

PMID- 16813869
TI  - Prognostic nomogram for renal insufficiency after radical or partial nephrectomy.
AB  - PURPOSE: We analyzed prognostic factors to predict renal insufficiency after
      partial or radical nephrectomy. We developed and performed internal validations
      of a postoperative nomogram for this purpose. We used a prospectively updated
      renal tumor database of more than 1,500 patients. MATERIALS AND METHODS: From
      July 1989 to October 2003, 161 partial nephrectomies and 857 radical
      nephrectomies performed at Memorial Sloan-Kettering Cancer Center for renal
      cortical tumors were analyzed. Computerized tomography images were reviewed by a
      single radiologist. Kidney volume was calculated using the ellipsoid formula, V =
      L1 x L2 x L3 x pi/6, where V represents volume and L represents length. Renal
      insufficiency was defined by 2 serum creatinine values greater than 2.0 mg/dl at
      least 1 month postoperatively. Tumor histology was not an exclusion criterion and
      yet we excluded cases of bilateral synchronous disease. Prognostic variables were
      preoperative serum creatinine, American Society of Anesthesiologists score,
      percent change in kidney volume after surgery, and patient age and sex. RESULTS:
      Renal insufficiency was noted in 105 of the 857 patients with radical nephrectomy
      (12.3%) and in 6 of the 161 with partial nephrectomy (3.7%) studied. Patients had
      a median followup of 21.2 months (maximum 157.9). The 7-year probability of
      freedom from renal insufficiency in the cohort was 79.1% (95% CI 74.6 to 83.6).
      The nomogram was designed based on a Cox proportional hazards regression model.
      Following internal statistical validation nomogram predictions appeared accurate
      and discriminating with a concordance index of 0.835. CONCLUSIONS: A nomogram was
      developed that can predict the 7-year probability of renal insufficiency in
      patients undergoing radical or partial nephrectomy.

PMID- 16813872
TI  - The outcome of patients on dialysis with upper urinary tract transitional cell
      carcinoma.
AB  - PURPOSE: Transitional cell carcinoma is the most common upper urinary tract
      cancer in Taiwanese patients on dialysis. It is a unique finding compared with
      Western countries. Unfortunately, the long-term outcomes of patients with upper
      urinary tract transitional cell carcinoma on dialysis are largely unknown. This
      study presents clinical outcome of patients on dialysis with upper urinary tract
      transitional cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed
      the medical records of all patients with upper urinary tract transitional cell
      carcinoma who had end stage renal disease and underwent dialysis. Traditional
      prognostic factors including age, sex, tumor grade, stage and tumor location were
      analyzed with respect to disease recurrence and survival. RESULTS: A total of 73
      patients were included in this study. The major complaints were painless gross
      hematuria and urethral bloody discharge. Disease relapsed in 40 (54.8%) patients
      at average time of 15 months (2 to 92). Univariate analysis failed to identify
      significant prognostic factors for recurrence. The average duration between
      primary and contralateral metachronous upper urinary tract transitional cell
      carcinoma recurrence was 36 months (range 5 to 96). Patients on dialysis with
      upper urinary tract transitional cell carcinoma who had previous or concurrent
      bladder tumor, or who had a history of recurrent bladder tumor, had high
      contralateral upper urinary tract transitional cell carcinoma recurrence. (p =
      0.038) The statistically significant prognostic factor for disease-free survival
      was pT stage (p = 0.041). CONCLUSIONS: Patients on dialysis with painless gross
      hematuria or bloody urethral discharge must undergo detail urinary system
      evaluation. Since patients with upper urinary tract transitional cell carcinoma
      on dialysis have a high recurrence rate and metachronous or even multiple, early
      synchronous tumor characteristics that may be missed by imaging, total urinary
      tract exenteration is a recommended therapeutic option.

PMID- 16813873
TI  - Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in
      steroid treated and immunocompromised patients.
AB  - PURPOSE: We assessed the safety and efficacy of intravesical bacillus Calmette
      Guerin instillations in steroid treated and immunocompromised patients. MATERIALS
      AND METHODS: We retrospectively reviewed the charts of 697 patients treated with
      bacillus Calmette-Guerin instillations at our institution from 1991 to 2004. In
      24 patients (3.5%) an underlying comorbidity directly affecting the immune system
      was diagnosed before bacillus Calmette-Guerin administration or steroids were
      administered at least 6 weeks before and at the time of bacillus Calmette-Guerin
      instillations. The immunosuppressive effect of steroids was assessed by the
      percent of lymphocytes. End points were the bacillus Calmette-Guerin response at
      6 months, defined as normal cystoscopy, cytology and biopsy when available, and
      treatment related toxicity. RESULTS: Four patients (17%) had active lymphoma or
      chronic lymphocytic leukemia during bacillus Calmette-Guerin administration and
      21 (88%) had a concurrent condition for which oral steroids (11), inhaled
      steroids (14) or oral and inhaled steroids (4) were administered. Patients
      treated with oral steroids had a lower percent of lymphocytes than patients
      treated with inhaled steroids and 15 age matched patients with high risk
      superficial bladder cancer and no steroid treatment (12.3% vs 17.5% and 18.6%,
      respectively). The overall bacillus Calmette-Guerin response rate at 6 months was
      58%. Ten of the 24 patients had disease recurrence and 3 had disease progression
      at a median followup of 63.5 months (IQR 19.5, 89). One patient treated with oral
      steroids had self-limited febrile disease and worsening of myalgia 48 hours after
      his third bacillus Calmette-Guerin cycle. No other systemic adverse event
      following bacillus Calmette-Guerin therapy was recorded and all patients
      completed scheduled treatments. CONCLUSIONS: Intravesical bacillus Calmette
      Guerin is a viable therapeutic option in patients with high risk superficial
      bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia,
      treatment with low dose oral steroids or treatment with inhaled steroids. The
      bacillus Calmette-Guerin response rate at 6 months and the side effects profile
      associated with bacillus Calmette-Guerin therapy in these patients were
      comparable to those in patients with no evidence of immunosuppression. Further
      studies are warranted to assess the safety and efficacy of bacillus Calmette
      Guerin instillations in critically immunocompromised patients.

PMID- 16813874
TI  - Cystectomy for transitional cell carcinoma of the bladder: results of a surgery
      only series in the neobladder era.
AB  - PURPOSE: We studied the effect of radical cystectomy for transitional cell
      carcinoma of the bladder on survival and failure patterns when the 2 surgical
      standards cystectomy and neobladder were combined, when possible. MATERIALS AND
      METHODS: A consecutive series of patients undergoing radical cystectomy with
      pelvic lymph node dissection for transitional cell carcinoma of the bladder with
      curative intent was analyzed. Patients with neoadjuvant radiotherapy/chemotherapy
      were excluded. Pathological characteristics based on the 2002 TNM system,
      recurrence-free/overall survival and metastatic patterns were determined.
      RESULTS: A total of 788 patients with a mean age +/- SD of 65 +/- 10 years and a
      mean followup of 53.5 months who underwent surgery between 1986 and 2003 were
      analyzed. A neobladder was constructed in 75.4% of patients. Ten-year recurrence
      free and overall survival rates were 59.1% and 44.9%, respectively. Positive
      lymph nodes were present in 143 patients (18%). The rate of recurrence-free
      survival at 5 years was 82.5% for pT2a pN0, 61.9% for pT2b and pT3a pN0, and
      53.1% for pT3b pN0 disease. Local and distant failure rates were 4% and 9.5% for
      organ confined tumors, 15.9% and 19.2% for nonorgan confined tumors, and 20.4%
      and 45.1% in patients with positive lymph nodes, respectively. CONCLUSIONS: In
      patients with organ confined, lymph node negative transitional cell carcinoma
      excellent survival data can be achieved as long as the tumor is limited to the
      inner half of the detrusor. These data on a large group of patients support early
      aggressive surgical management for invasive bladder cancer. The results of this
      surgery only series may serve as a reference for other treatment modalities for
      bladder cancer.

PMID- 16813876
TI  - Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of
      bladder cancer following radical cystectomy.
AB  - PURPOSE: We compared and evaluated clinical outcomes in patients with
      pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with
      transitional cell carcinoma following radical cystectomy and urinary diversion.
      MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including
      244 males (78%) and 67 females, were found to have pathological muscle invasive
      (pT2) bladder cancer following radical cystectomy. Of this group 147 patients
      (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive
      tumors. Overall 242 patients had no evidence of lymph node metastasis, including
      127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had
      lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a
      median followup of 14.3 years (range 0 to 30.1) clinical outcomes were
      determined, including recurrence-free and overall survival, and local vs distant
      recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free
      and overall survival rates were 72% and 47%, respectively. There was a
      significantly higher risk of node positive disease with pT2b vs pT2a tumors (30%
      vs 14%, p <0.001). No significant difference was observed in 10-year recurrence
      free survival in patients with pT2a node negative vs pT2b node negative tumors
      (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive
      tumors, no significant difference was observed in 10-year recurrence-free
      survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly
      higher in patients with pT2 lymph node negative tumors than in those with pT2
      lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences
      remained significant when stratified by pT2a and pT2b node negative vs positive
      disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2
      disease, while 69 (22%) had distant metastatic disease. In patients with
      recurrence the local or distant recurrence site was not associated with tumor
      stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p =
      0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical
      cystectomy there is a higher risk of lymph node positive disease in deep muscle
      (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was
      observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep)
      muscle invasive tumors when controlling for lymph node status. Recurrence-free
      survival is significantly improved in patients with pT2 lymph node negative
      tumors compared to survival in those with pT2 lymph node positive tumors.
      Patients with muscle invasive (pT2), lymph node negative tumors have excellent
      clinical outcomes following cystectomy, while those with muscle invasive (pT2),
      lymph node positive tumors have higher recurrence rates and should be considered
      for adjuvant treatment protocols.

PMID- 16813878
TI  - Randomized prospective phase III trial of difluoromethylornithine vs placebo in
      preventing recurrence of completely resected low risk superficial bladder cancer.
AB  - PURPOSE: Ornithine decarboxylase catalyzes the rate limiting step in polyamine
      synthesis and its activity can be inhibited by difluoromethylornithine, which has
      been shown in preclinical studies, to prevent bladder cancer. MATERIALS AND
      METHODS: To assess the ability of difluoromethylornithine to prevent recurrence
      of low risk superficial bladder cancer, 454 patients with newly diagnosed (283)
      or occasionally recurrent (171), stage Ta (425) or T1 (29), grade 1 (263) or
      grade 2 (191), completely resected urothelial cancer were randomized to receive 1
      gm difluoromethylornithine daily or placebo for 1 year. Patients were followed
      with cystoscopy every 3 months for 2 years and then semiannually for 2 years or
      until first recurrence. Index and recurrent tumors underwent central pathology
      review. RESULTS: No serious drug related toxicities were seen in either arm. Two
      patients died of bladder cancer at 2 and 4 years after randomization, both in the
      difluoromethylornithine arm. At 42 months followup, 103 patients in the
      difluoromethylornithine arm (46%) and 97 in the placebo arm (43%) (p = 0.30)
      experienced at least 1 tumor recurrence. Over 73% of recurrences occurred within
      1 year in each arm. Each arm had similar responses for each stratification
      factor. During the 42 months of followup, 10 (4.4%) difluoromethylornithine and 9
      (3.9%) placebo treated patients had progression to TIS or grade 3 disease, and 2
      (0.9%) in the difluoromethylornithine arm and none in the placebo arm developed
      stage T2+ cancers. CONCLUSIONS: A year of difluoromethylornithine did not prevent
      recurrence of completely resected low risk superficial bladder cancer, when
      started shortly after surgery.

PMID- 16813879
TI  - Prostate specific antigen testing in men older than 75 years in the United
      States.
AB  - PURPOSE: Although there is general agreement that men older than 75 years are
      unlikely to benefit from prostate specific antigen testing, patient reported
      testing rates in these patients exceed 30%. We examined physician reported PSA
      testing in elderly men, and physician and practice characteristics associated
      with testing. MATERIALS AND METHODS: Using the 1999 to 2002 National Ambulatory
      Medical Care Survey, a nationally representative sample of outpatient visits to
      nonfederal office based physicians, we measured rates of prostate specific
      antigen testing by age group in men without prostate cancer who were 40 years or
      older and who visited outpatient family medicine, internal medicine or urology
      clinics. RESULTS: An estimated 42.3 million prostate specific antigen tests were
      performed from 1999 to 2002, of which 5.91 million (14.0%) were performed in men
      older than 75 years. The population based testing rate was 6.1% in patients 40 to
      49-year-old, 26.0% in patients 50 to 75-year-old and 27.8% in patients older than
      75 years. Urologists performed 35.4% of prostate specific antigen tests in men
      older than 75 years. Controlling for sociodemographic variables physicians with a
      laboratory on site were more likely to perform a prostate specific antigen test
      (OR 1.35, 95% CI 1.07 to 1.71). In men older than 75 years the odds of prostate
      specific antigen testing were 1.58 times higher (95% CI 1.01 to 2.50) in
      practices with a laboratory on site. CONCLUSIONS: Up to a third of men older than
      75 years undergo prostate specific antigen testing despite an average life
      expectancy of less than 10 years. Physician and practice characteristics are
      associated with prostate specific antigen PSA testing.

PMID- 16813880
TI  - Black race does not independently predict adverse outcome following radical
      retropubic prostatectomy at a tertiary referral center.
AB  - PURPOSE: There is controversy in the literature as to whether black race is
      associated with poorer oncological outcomes among men undergoing radical
      prostatectomy for clinically localized prostate cancer. To address this issue we
      examined the outcomes of a cohort of black and white men treated by multiple
      surgeons at our institution. MATERIALS AND METHODS: The study population
      consisted of 4,962 white and 326 black men treated with anatomical radical
      retropubic prostatectomy between 1988 and 2004 by 10 different surgeons at the
      Johns Hopkins Hospital, a tertiary care referral center. We evaluated the
      association between race and adverse pathological features, and biochemical
      progression. RESULTS: Black men had significantly higher preoperative serum
      prostate specific antigen (mean 7.2 vs 6.0 ng/ml, p <0.001), body mass index
      (median 27.4 vs 26.3 kg/m, p <0.001) and incidence of higher grade disease
      (Gleason sum 4 + 3 or greater) on prostate biopsy (17% vs 14%, p = 0.011). After
      adjustment for multiple clinical variables there was no statistically significant
      association between race and the adverse pathological characteristics of high
      grade disease, positive surgical margins, extraprostatic extension or seminal
      vesicle invasion. Black race was associated with a significantly increased risk
      of biochemical progression on univariate analysis (HR 1.52, 95% CI 1.16-2.00, p =
      0.002). However, after adjusting for clinical and pathological characteristics,
      black race was not an independent predictor of biochemical progression (HR 1.09,
      95% CI 0.81-1.45, p = 0.578). CONCLUSIONS: Black men were more likely to be obese
      and present with adverse preoperative clinical features at a younger age, and
      have a higher rate of biochemical progression. However, on multivariate analysis
      black race was not an independent predictor of adverse pathological outcome or
      biochemical recurrence. Further efforts are needed to detect prostate cancer
      earlier among black men.

PMID- 16813881
TI  - The effect of androgen deprivation therapy on fasting serum lipid and glucose
      parameters.
AB  - PURPOSE: Although prostate cancer specific mortality is decreasing, there is
      little effect on overall mortality in this population, suggesting the possibility
      of an increased risk of death from nonprostate cancer related causes. Androgen
      deprivation therapy could adversely affect cardiovascular health. We investigated
      changes in lipid and glucose during androgen deprivation therapy. MATERIALS AND
      METHODS: We performed an exploratory analysis of pooled data from 3 prospective
      clinical trials aimed at achieving medical castration by comparing the
      gonadotropin releasing hormone antagonist abarelix, the gonadotropin releasing
      hormone agonist leuprolide acetate and leuprolide acetate plus the antiandrogen
      bicalutamide. Most patients were treated in the neoadjuvant setting or because of
      biochemical recurrence. Fasting serum lipid, glucose and hemoglobin A1C were
      determined in 1,102 men at baseline, and on treatment days 85 and 169. In the
      current study men were categorized into 3 treatment groups according to the type
      of androgen deprivation therapy, that is leuprolide acetate, leuprolide acetate
      plus bicalutamide or abarelix, and statin therapy. RESULTS: Significant increases
      in total cholesterol, triglyceride and high density lipoprotein-cholesterol were
      observed in patients on leuprolide acetate or abarelix but not in patients on
      leuprolide acetate plus bicalutamide. Consistent changes in low density
      lipoprotein-cholesterol were not detected. Increased total cholesterol was
      usually due to an increase in high density lipoprotein-cholesterol. Hemoglobin
      A1C increased from baseline to day 85 only and there were no significant changes
      in fasting glucose measurements. The type of androgen deprivation therapy did not
      affect these parameters. CONCLUSIONS: Short-term androgen deprivation therapy
      affects serum lipid and hemoglobin A1C independent of statin therapy.

PMID- 16813882
TI  - Use of hormonal therapy in men with metastatic prostate cancer.
AB  - PURPOSE: Bilateral orchiectomy or luteinizing hormone releasing hormone agonists
      represent the standard of care for metastatic prostate cancer. In this population
      based study we assessed the use rates of these therapies in men who died of
      prostate cancer. MATERIAL AND METHODS: A total of 9,110 men 65 years or older who
      died of prostate cancer in 1991 to 2000 were identified through the population
      based Surveillance, Epidemiology and End Results, and Medicare linked database to
      determine hormonal therapy use rates. A modified Poisson regression model was
      used to estimate the adjusted effects of various factors associated with hormone
      use. RESULTS: Approximately 38% of black and 25% of white men did not receive
      hormonal therapy before dying of prostate cancer. After adjusting for cancer
      status at diagnosis and other potential confounding factors black race and
      residence in low income areas were associated with lower hormonal therapy use
      (relative risk 0.73, 95% CI 0.67 to 0.80 and 0.91, 95% CI 0.85 to 0.98,
      respectively). Hormonal therapy use was most comprehensive in the Northeast.
      CONCLUSIONS: A substantial number of men who die as a consequence of prostate
      cancer never receive hormonal therapy. The use of hormonal therapy varies
      significantly. Further studies are warranted to determine factors that may be
      associated with the incomplete use of hormonal therapy for metastatic prostate
      cancer.

PMID- 16813883
TI  - Intensity of androgen and epidermal growth factor receptor immunoreactivity in
      samples of radical prostatectomy as prognostic indicator: correlation with
      clinical data of long-term observations.
AB  - PURPOSE: We analyzed the potential prognostic significance of the
      immunohistochemical expression of androgen and growth factor receptors determined
      in prostatectomy specimens of patients with prostate cancer. MATERIALS AND
      METHODS: A cohort of 211 patients with locally confined prostate cancer treated
      with radical prostatectomy with or without antiandrogen pretreatment between
      January 1, 1990 and August 31, 1996 was observed prospectively. Prostatectomy
      samples were processed immunohistochemically to visualize androgen and growth
      factor receptors, of which immunoreaction intensity was scored relative to that
      of positive control tissue. Clinical postoperative data were processed using the
      Kaplan-Meier method, log rank test, and univariate and multivariate explorative
      Cox modeling to evaluate the contribution to overall and relapse-free survival.
      RESULTS: There were statistical dependencies between the androgen receptor and
      epidermal growth factor receptor staining indexes. Following data stratification
      according to the epidermal growth factor receptor staining index the prognosis
      associated with a low androgen receptor staining index was worse than that with a
      higher androgen receptor staining index. Cox regression analysis for relapse-free
      survival confirmed that the risk factors low androgen receptor and increased
      epidermal growth factor receptor staining were associated with significantly
      increased relative risk. Univariate Kaplan-Meier analysis showed that patients
      with grade 3 carcinoma had a worse prognosis than those with better
      differentiated carcinoma, whereas antiandrogen pretreatment had no influence on
      overall survival or relapse-free survival. CONCLUSIONS: Using a multivariate
      proportional hazards regression model for data on a cohort of 211 patients with
      68 showing relapse/progress or death from disease a low intensity of androgen
      receptor staining indicated a poor prognosis.

PMID- 16813884
TI  - Breast cancer as a second primary in patients with prostate cancer--estrogen
      treatment or association with family history of cancer?
AB  - PURPOSE: In a large population based study we reported an increased risk of male
      breast cancer after prostate cancer. In the current study we performed a
      comprehensive investigation of whether treatment for prostate cancer and/or
      family history is responsible for the excess risk. MATERIALS AND METHODS: This
      study had 2 parts. 1) We performed a nested case-control study in 41 men who had
      previously been identified with first prostate cancer, followed by male breast
      cancer and in 81 matched controls with prostate cancer only. The medical records
      of these men were retrieved and clinical data such as stage, grade and treatment
      were extracted. 2) We also performed a family study including relatives of men
      with a diagnosis of prostate as well as breast cancer, irrespective of which was
      first. The 878 relatives were identified through parish offices and linked to the
      Swedish Cancer Registry to evaluate the occurrence of breast, prostate and other
      cancers and calculate if there were any excess risks for different cancers.
      RESULTS: Cases with prostate plus breast cancer received estrogen treatment more
      often than controls with prostate cancer only (p = 0.03). The period of estrogen
      treatment was longer in the cases, although it was not statistically significant.
      Mean time from prostate cancer diagnosis to breast cancer diagnosis was 47.6
      months. Cases and controls did not differ in grade or stage. In the family study
      an increased risk of prostate cancer was found in relatives (SIR 2.14, 95% CI
      1.09 to 3.18). For other cancers no significantly increased risks were found. In
      2 families pedigree analysis using the BRCAPRO program
      (http://www3.utsouthwestern.edu/cancergene/) revealed an estimated 100% and 49%
      probability in families 1 and 2, respectively, that the proband was a BRCA2
      carrier. CONCLUSIONS: Our data suggest that most of the increased risk of breast
      cancer following prostate cancer can be explained by estrogen treatment. However,
      in a small number of men with prostate as well as breast cancer pedigree analysis
      suggests that BRCA2 mutation might be the underlying cause.

PMID- 16813885
TI  - Long-term followup of a randomized study of locally advanced prostate cancer
      treated with combined orchiectomy and external radiotherapy versus radiotherapy
      alone.
AB  - PURPOSE: In a randomized study we compared the combination of orchiectomy and
      radiotherapy to radiotherapy alone as treatment for locally advanced prostate
      cancer. Patients who were treated only with radiotherapy initially underwent
      castration therapy at clinical progression, providing the opportunity to compare
      immediate vs deferred endocrine intervention. MATERIALS AND METHODS: In this
      prospective study 91 patients with locally advanced prostate cancer were
      randomized to receive external beam radiotherapy (46) or combined orchiectomy and
      radiotherapy (45) after surgical lymph node staging. Survival rates were
      calculated. RESULTS: During 14 to 19 years of followup 87% of the patients in the
      radiotherapy group and 76% in the combined orchiectomy and radiotherapy group
      died (log rank p = 0.03). Prostate cancer mortality was 57% and 36%, respectively
      (log rank p = 0.02). The difference in favor of combined treatment was mainly
      caused by lymph node positive tumors. For node negative tumors there was no
      significant difference in the survival rates. CONCLUSIONS: Immediate androgen
      deprivation should be considered instead of deferred endocrine treatment started
      at clinical progression for prostate cancer with spread to regional lymph nodes.
      While awaiting evidence from randomized trials, one should consider full dose
      radiotherapy for local control of locally advanced prostate cancer even when it
      is lymph node positive.

PMID- 16813886
TI  - Locally advanced prostate cancer treated with concomitant radiation and 5
      fluorouracil: Southwest Oncology Group Study 9024.
AB  - PURPOSE: Radiation is considered the standard treatment for locally advanced (T3
      and T4) prostate cancer but cure with radiation alone is infrequent. Studies have
      shown that adding androgen ablation improves the results but there is still much
      room for improvement. We performed a phase II multi-institutional study to
      explore the feasibility of concomitant chemoradiotherapy. MATERIALS AND METHODS:
      Eligible patients had prostate cancer with clinical evidence of invasion through
      the prostatic capsule or into the seminal vesicles without evidence of nodal or
      distant metastasis. Prior prostatectomy was not allowed and patients could not be
      candidates for surgical resection due to medical reasons or refusal of surgery.
      Radiation consisted of 7,020 cGy in 39 fractions. Continuous infusion 5
      fluorouracil at a dose of 200 mg/m2 daily was started on day 1 and continued 7
      days weekly until the last day of radiation. RESULTS: All 30 eligible patients
      were evaluated for toxicity. Diarrhea was the most common toxicity with grade 3
      and 4 diarrhea in 2 and 1 patients, respectively. The only other grade 4 toxicity
      was hemorrhagic cystitis in 1 patient. There was 1 incident each of grade 3
      stomatitis, congestive heart failure, edema, proctitis and hematuria. No patient
      with grade 3 or 4 toxicity required treatment delay. Ten patients (33%) achieved
      a negative biopsy and 13 (43%) achieved prostate specific antigen less than 1.0
      ng/ml. Six patients (20%) achieved a complete response, defined as negative
      biopsy and prostate specific antigen less than 1.0 (95% CI 8 to 39). Patients
      without any biopsies or without prostate specific antigen followup were assumed
      to be nonresponders. CONCLUSIONS: Toxicity was acceptable. The modest response
      rate indicates that better chemotherapy that improves local and systemic failure
      is necessary to improve the results. This study confirms the feasibility of a
      combined chemoradiotherapy approach.

PMID- 16813888
TI  - Pathological outcomes and biochemical progression in men with T1c prostate cancer
      undergoing radical prostatectomy with prostate specific antigen 2.6 to 4.0 vs 4.1
      to 6.0 ng/ml.
AB  - PURPOSE: Recent studies have suggested that the cut point for recommending
      prostate biopsy among men with a normal digital rectal examination should be
      greater than 2.5 ng/ml as opposed to the more traditional greater than 4.0 ng/ml.
      We compared outcomes between men with clinical stage T1c disease undergoing
      radical prostatectomy who had a low vs slightly increased prostate specific
      antigen. MATERIALS AND METHODS: The study population consisted of 2,896 men
      treated with radical prostatectomy between 1985 and 2004 at a tertiary care
      referral center with clinical stage T1c disease and a pre-biopsy prostate
      specific antigen between 2.6 and 6.0 ng/ml. Using multivariate analysis we
      evaluated the association between pre-biopsy prostate specific antigen 2.6 to 4.0
      ng/ml (784) vs 4.1 to 6.0 ng/ml (2,112), and pathological outcomes and
      biochemical progression. RESULTS: After adjusting for multiple clinical and
      pathological characteristics, lower preoperative serum prostate specific antigen
      values were associated with decreased odds of Gleason score 7 or greater in the
      surgical specimen (p = 0.004), positive surgical margins (p = 0.02) and
      extraprostatic extension (p = 0.001). There was no significant association
      between these preoperative prostate specific antigen groups and odds of seminal
      vesicle invasion (p = 0.47) or lymph node metastasis (p = 0.90). Among the 1,534
      men with followup information available there was a trend for increased risk of
      biochemical progression associated with a higher preoperative prostate specific
      antigen, although this trend did not reach statistical significance (relative
      risk 1.48, 95% CI 0.69-3.19, p = 0.31). CONCLUSIONS: In the current study of men
      with clinical stage T1c treated with radical prostatectomy a lower preoperative
      prostate specific antigen was associated with significantly more favorable
      pathological findings. Whether this degree of improved outcomes justifies the
      limitations associated with decreasing the prostate specific antigen cut point
      (eg increased biopsies performed and diagnosis of insignificant cancers) remains
      to be determined.

PMID- 16813889
TI  - Detectable prostate specific antigen between 60 and 120 days following radical
      prostatectomy for prostate cancer: natural history and prognostic significance.
AB  - PURPOSE: Following radical retropubic prostatectomy for prostate cancer, if the
      serum prostate specific antigen fails to become undetectable, occult
      micrometastatic disease is suspected. We assessed the natural history of disease
      progression, and predictors of recurrence and survival in this group of patients.
      MATERIALS AND METHODS: We identified 303 men treated with radical retropubic
      prostatectomy for prostate cancer between 1990 and 1999, who had a detectable
      prostate specific antigen between 60 and 120 days postoperatively. Systemic
      recurrence-free and cancer specific survival were estimated using the Kaplan
      Meier method, and analyzed using Cox proportional hazards models. RESULTS:
      Clinical and pathological features were more adverse among men whose
      postoperative prostate specific antigen was detectable. These men had poorer
      systemic recurrence-free survival and cancer specific survival compared to men
      with an undetectable postoperative prostate specific antigen, and even men whose
      prostate specific antigen subsequently became detectable. These differences
      persisted after multivariate adjustment for preoperative prostate specific
      antigen, specimen Gleason score, seminal vesicle and margin status. With a median
      followup of 8.5 years, 50 systemic recurrences and 26 deaths from cancer were
      observed. Gleason score and the prostate specific antigen doubling time were
      multivariate predictors of systemic recurrence, while Gleason score, margin
      status and seminal vesicle invasion were predictors of death from cancer.
      CONCLUSIONS: A detectable prostate specific antigen immediately following radical
      retropubic prostatectomy confers an increased risk of progression and death, but
      only in a subset of patients, who may be identified on the basis of pathological
      features and prostate specific antigen doubling time. In future such patients may
      be suitable for trials of systemic therapy.

PMID- 16813890
TI  - Long-term outcome following radical prostatectomy in men with clinical stage T3
      prostate cancer.
AB  - PURPOSE: We evaluated patients at our institution who underwent radical
      prostatectomy for clinical stage T3 prostate cancer to determine their long-term
      clinical outcomes. MATERIALS AND METHODS: We reviewed our prospective surgical
      database and identified 176 men who underwent radical retropubic prostatectomy
      for clinical stage T3 prostate cancer from 1983 to 2003. Clinical and
      pathological data were reviewed and evaluated in a Cox proportional hazards model
      to determine preoperative predictors of biochemical recurrence. Clinical
      progression following biochemical recurrence was evaluated and clinical failure
      was defined as the development of clinical metastases or progression to hormone
      refractory prostate cancer. RESULTS: Of the 176 patients with cT3 prostate cancer
      64 (36%) received neoadjuvant hormonal therapy. At a mean followup of 6.4 years
      84 (48%) patients had disease recurrence with a median time to biochemical
      recurrence of 4.6 years. The actuarial 10-year probability of freedom from
      recurrence was 44%. On multivariate analysis biopsy Gleason score, pretreatment
      serum prostate specific antigen and year of surgery were independent predictors
      of biochemical recurrence. Neoadjuvant hormonal therapy was not a significant
      predictor of biochemical recurrence. Following biochemical recurrence clinical
      failure developed in 30 of 84 (36%) men with a median time of 11 years. Overall
      the 5, 10 and 15-year probabilities of death from prostate cancer were 6%, 15%
      and 24%, respectively. CONCLUSIONS: More than half (52%) of our patients remained
      free of disease recurrence following radical prostatectomy. In our series
      neoadjuvant hormonal therapy offered no advantage with respect to disease
      recurrence. Radical prostatectomy remains an integral component in the treatment
      of select patients with clinical stage T3 prostate cancer.

PMID- 16813891
TI  - 25-year prostate cancer control and survival outcomes: a 40-year radical
      prostatectomy single institution series.
AB  - PURPOSE: We report on 25-year cancer control and survival outcomes after radical
      prostatectomy in a single center series of patients treated during a 40-year
      period. MATERIALS AND METHODS: Between 1954 and 1994, 787 consecutive patients
      underwent radical prostatectomy at Virginia Mason Medical Center in Seattle,
      Washington. Kaplan-Meier 25-year probabilities of prostate cancer specific,
      overall, prostate specific antigen progression-free, local and distant
      progression-free survival were determined. Multivariate Cox regression models
      addressed prostate cancer specific mortality. RESULTS: Prostate cancer specific
      survival, overall survival, prostate specific antigen progression-free survival,
      local and distant progression-free survival ranged from 99.0% to 81.5%, 93.5% to
      19.3%, 84.8% to 54.5%, 95.3% to 87.8% and 95.9% to 78.2%, respectively. In
      univariate analyses pathological stage, surgical margin status, pathological
      Gleason sum, delivery of hormonal therapy and radiotherapy represented
      statistically significant predictors of prostate cancer specific mortality (all p
      < or =0.001). In multivariate analyses only Gleason sum (p = 0.03) and delivery
      of hormonal therapy (p < 0.001) remained significant. CONCLUSIONS: This is one of
      the most mature radical prostatectomy series. It demonstrates that long-term
      biochemical cancer control outcomes after radical prostatectomy might be
      suboptimal. However, local and distant control outcomes are excellent, and cancer
      specific mortality is minimal even 25 years after surgery.

PMID- 16813892
TI  - Penis conserving treatment for T1 and T2 penile carcinoma: clinical implications
      of a local recurrence.
AB  - PURPOSE: We evaluated our experience with primary tumor treatment for T1 and T2
      penile squamous cell carcinoma and discussed the clinical implications of a local
      recurrence. MATERIALS AND METHODS: The primary tumor treatment and clinical
      course of 257 patients with T1 or T2 penile carcinoma were evaluated. Primary
      tumor treatment consisted of penis preservation in 157 and (partial) amputation
      in 100 patients. Median followup was 106 months (range 16 to 541). RESULTS: The 5
      year local recurrence-free estimate after penis preservation was similar for T1
      and T2 tumors (log rank test p = 0.1) and overall 63% (CI: 54%-72%) compared to
      88% (CI: 81%-95%) for partial amputation (log rank test p = 0.0003). In case of a
      local recurrence after penis preserving treatment, local control could be
      achieved in 94% (51 of 54) of cases. Of patients with T1 tumors treated with
      penis preservation, regional recurrence developed in 33% (7 of 21) of patients
      with local recurrence compared to only 6% (3 of 47) of patients without local
      recurrences (Fisher's exact test p = 0.005). Of the patients with T2 tumors
      treated with penis preservation, regional recurrence developed in 27% (9 of 33)
      of patients with local recurrence compared to 27% (12 of 45) of patients without
      local recurrence (chi-square test p = 0.96). Of 10 patients with a local
      recurrence after partial amputation of the penis, 9 died of disease. CONCLUSIONS:
      The incidence of local recurrence increases with penis preservation but can be
      treated accurately in most cases. Local recurrences can signify lymphatic
      regional spread. A local recurrence after penile amputation carries a poor
      prognosis.

PMID- 16813894
TI  - Efficiency of questionnaires used to screen for interstitial cystitis.
AB  - PURPOSE: Questionnaires for the evaluation of interstitial cystitis are widely
      used, but their value in discriminating interstitial cystitis from other
      diagnoses among patients with urological symptoms has not been determined. We
      assessed the validity of 2 frequently used interstitial cystitis questionnaires
      the O'Leary-Sant Symptom Index and Problem Index and the Pain, Urgency, Frequency
      Symptom Scale-for screening for interstitial cystitis. MATERIALS AND METHODS: The
      Pain, Urgency, Frequency Symptom Scale and the O'Leary-Sant Symptom Index and
      Problem Index were administered to the same 220 patients at a urology clinic
      before diagnosis. Questionnaire scores between patients with and without
      interstitial cystitis, as well as among diagnostic groups, were compared by
      parametric and nonparametric analyses. Receiver operating characteristic curves
      were constructed to determine the efficiency of each questionnaire in
      discriminating between patients with and without interstitial cystitis. RESULTS:
      Interstitial cystitis was distinguishable from the other diagnoses using both
      questionnaires (p <0.001). Separate analyses of bother and symptom scores yielded
      similar results. Receiver operating characteristic curves demonstrated the Pain,
      Urgency, Frequency Symptom Scale to be more efficient than the O'Leary-Sant
      Symptom Index and Problem Index in detecting interstitial cystitis in this
      population with an optimal cutoff value of 13 or greater. CONCLUSIONS: While the
      Pain, Urgency, Frequency Symptom Scale and the O'Leary-Sant Symptom Index and
      Problem Index questionnaires distinguish interstitial cystitis from other urinary
      tract pathologies, neither questionnaire demonstrates sufficient specificity to
      serve as the sole diagnostic indicator. These questionnaires should not be used
      to define interstitial cystitis, but can be used to screen patients with urinary
      tract symptoms to identify those who should be further examined for interstitial
      cystitis or to follow those who have already been diagnosed.

PMID- 16813895
TI  - Prevalence of prostatitis-like symptoms in a managed care population.
AB  - PURPOSE: We calculated the prevalence of symptoms typically associated with
      chronic prostatitis/chronic pelvic pain syndrome in men in a managed care
      population in the Pacific Northwest. MATERIALS AND METHODS: A questionnaire
      mailing to 5,000 male enrollees 25 to 80 years old in the Kaiser Permanente
      Northwest (Portland, Oregon) health plan was performed. The questionnaires
      included screening questions about the presence, duration and severity of pelvic
      pain, and the National Institutes of Health Chronic Prostatitis Symptom Index.
      Chronic prostatitis/chronic pelvic pain syndrome symptoms were defined in 2 ways:
      1) presence of any of the following for a duration of 3 or more months: pain in
      the perineum, testicles, tip of penis, pubic or bladder area, dysuria,
      ejaculatory pain; and 2) perineal and/or ejaculatory pain, and a National
      Institutes of Health Chronic Prostatitis Symptom Index total pain score of 4 or
      more. Prevalence estimates were age adjusted to the total Kaiser Permanente
      Northwest male population. RESULTS: A total of 1,550 questionnaires were
      returned. The prevalence of chronic prostatitis/chronic pelvic pain syndrome
      symptoms was 7.5% for definition 1 and 5.9% for definition 2. Mean National
      Institutes of Health Chronic Prostatitis Symptom Index scores were 17 for
      definitions 1 and 2. Of those with prostatitis-like symptoms, 30% met criteria
      for having both definitions present. The prevalence of prostatitis-like symptoms
      using either of the 2 diagnoses was 11.2%. CONCLUSIONS: This population based
      study indicates that approximately 1 in 9 men have prostatitis-like symptoms.
      Application of 2 different definitions for prostatitis-like symptoms identified
      unique groups of men, with limited overlap in the groups.

PMID- 16813897
TI  - Renal function in patients with nephrolithiasis.
AB  - PURPOSE: We describe kidney function, as measured by creatinine clearance in
      stone formers, and classified by type of stone formed and systemic etiologies of
      stone formation. MATERIALS AND METHODS: The mean of 3 pretreatment 24-hour
      creatinine clearance measurements in each of 1,856 stone formers and creatinine
      clearance in 153 normal individuals were used. Clearance was adjusted for patient
      sex, age and body weight using general linear modeling. RESULTS: As a group, all
      stone formers had decreased clearance adjusted for age, sex and body weight
      compared to that in normal individuals. Although clearance was particularly low
      in cystine and struvite stone formers, they were below normal in even common CaOx
      stone formers. CONCLUSIONS: As a rule, patients with kidney stones do not have
      normal kidney function. In clinical management all efforts must be made to
      minimize renal injury, balancing the risks of obstruction from stones against
      those of urological procedures.

PMID- 16813899
TI  - Frequency of ureteroscope damage seen at a tertiary care center.
AB  - PURPOSE: There is controversy regarding ureteroscope durability. Little is known
      regarding the subsequent durability of a flexible ureteroscope after major damage
      has been incurred and the ureteroscope has been repaired. Maintenance and repair
      are associated with significant cost. We reviewed and assessed the frequency and
      cause of ureteroscope damage at our medical center. MATERIALS AND METHODS: From
      December 2001 we prospectively recorded the specific use of all ureteroscopes and
      any resultant damage at a single tertiary care institution. We then reviewed a
      total of 601 ureteroscopic cases involving 654 semirigid and flexible
      ureteroscope uses from December 2001 to November 2004. Cases were performed by
      multiple residents and fellows under the supervision of 3 attending urologists
      (CML, RJL and VGB). Retrograde and antegrade cases involving stones, urothelial
      carcinoma, strictures and diagnostic evaluations were included. Repairs for the
      respective ureteroscopes were performed by the original manufacturer. RESULTS: A
      total of 53 reports of damage (8.1% of total uses) were recorded. Major damage
      when the scope was deemed unusable and required repair was seen in 39 cases
      (6.0%). Four newly purchased flexible ureteroscopes were entered into the study
      and they provided 40 to 48 uses before the initial repair was needed. After these
      new ureteroscopes underwent comprehensive repair for major damage they averaged
      only 11.1 uses (median 8) before needing repair again. Older model ureteroscopes
      that underwent repair before being entered into our study averaged between 4.75
      and 7.7 uses before being sent for subsequent repair. Of the total of 39
      breakages 39 for which ureteroscopes were sent for repair 14 (35.9%) were the
      result of errant laser firing, 11 (28.2%) were the result of excessive torque, 8
      (20.5% 8) were the result of decreased flexion in the distal tip or another loss
      of function without obvious iatrogenic cause, 3 (7.7%) were the result of
      multifocal catastrophic damage involving laser firing and excessive torque, and 3
      (7.7%) were the result of cleaning and processing outside of the ureteroscopy
      suite. CONCLUSIONS: The most important risk factors for predicting the number of
      uses expected from a ureteroscope at our institution is ureteroscope age and
      whether the ureteroscope has undergone comprehensive repair as the result of
      prior damage. Our analysis suggests that after damage occurs to a ureteroscope
      more damage occurs with greater frequency. The cost of maintaining previously
      used ureteroscopes should be carefully considered in comparison to the cost of
      purchasing a new ureteroscope.

PMID- 16813901
TI  - Dorsal graft urethroplasty for female urethral stricture.
AB  - PURPOSE: Urethral strictures in females are uncommon, and treatment options and
      outcome are not well-defined with scanty reports. We describe a new method of
      urethroplasty for the repair of female urethral stricture. MATERIALS AND METHODS:
      Three 60-year-old females, each with a history of recurrent urinary tract
      infections and obstructive voiding symptoms due to urethral stricture, underwent
      urethroplasty with a dorsal vaginal or buccal mucosal graft. The dorsal aspect of
      the distal urethra was dissected from the surrounding tissue through a
      suprameatal incision and the urethral wall was incised through the stricture at
      the 12 o'clock position. A 1.5 cm wide free graft was harvested from the vaginal
      wall or buccal mucosa in 1 case, and the mucosal surface was placed upon the
      urethral lumen and sutured with a running 5-zero polyglactin suture to the open
      urethra. Indwelling 18Fr urethral and 16Fr suprapubic catheters were left in
      place for 2 and 3 weeks, respectively. RESULTS: No additional treatment was
      required during the 1, 8 and 27 months of followup. All patients had normal
      micturition following catheter removal. CONCLUSIONS: Dorsal graft urethroplasty
      is feasible and effective for the correction of persistent female urethral
      stricture.

PMID- 16813903
TI  - Anastomotic fibrous ring as cause of stricture recurrence after bulbar onlay
      graft urethroplasty.
AB  - PURPOSE: We retrospectively reviewed patterns of failure after bulbar
      substitution urethroplasty. In particular we investigated the prevalence and
      location of anastomotic fibrous ring strictures occurring at the apical
      anastomoses between the graft and urethral plate after 3 types of onlay graft
      techniques. MATERIALS AND METHODS: We reviewed the records of 107 patients who
      underwent bulbar urethroplasty between 1994 and 2004. Mean patient age was 44
      years. Patients with lichen sclerosus, failed hypospadias repair or urethroplasty
      and panurethral strictures were excluded. A total of 45 patients underwent dorsal
      onlay skin graft urethroplasty, 50 underwent buccal mucosa onlay graft
      urethroplasty and 12 underwent augmented end-to-end urethroplasty. The clinical
      outcome was considered a success or failure at the time that any postoperative
      procedure was needed, including dilation. Mean followup was 74 months (range 12
      to 130). RESULTS: Of 107 cases 85 (80%) were successful and 22 (20%) failed.
      Failure in 12 patients (11%) involved the whole grafted area and in 10 (9%) it
      involved the anastomotic site, which was distal and proximal in 5 each.
      Urethrography, urethral ultrasound and urethroscopy were fundamental for
      determining the difference between full-length and focal extension of re
      stricture. Failures were treated with multistage urethroplasty in 12 cases,
      urethrotomy in 7 and 1-stage urethroplasty in 3. Of the patients 16 had a
      satisfactory final outcome and 6 underwent definitive perineal urinary diversion.
      CONCLUSIONS: The prevalence and location of anastomotic ring strictures after
      bulbar urethroplasty were uniformly distributed in after 3 surgical techniques
      using skin or buccal mucosa. Further studies are necessary to clarify the
      etiology of these fibrous ring strictures.

PMID- 16813905
TI  - Fate of the leftover bladder after supravesical urinary diversion for benign
      disease.
AB  - PURPOSE: We studied the fate of the leftover bladder in patients who underwent
      supravesical urinary diversion without cystectomy for benign pathology. MATERIALS
      AND METHODS: This retrospective study was performed in 9 males and 15 females
      with a median age of 59 years in whom supravesical urinary diversion was
      performed for various benign conditions from 1996 to 2004. These conditions were
      incontinence, acontractile bladder, radiation and/or hemorrhagic cystitis, and
      neuropathic bladder. Median followup was 48 months. RESULTS: Of the patients 13
      (54%) experienced problems with the retained bladder, 2 (8%) presented with
      urethral bleeding, which resolved by conservative means, and 11 (46%) had
      infective complications, which resolved with expectant treatment in 3 (12%).
      However, 8 patients (33%) had frank pyocystis and 3 (12%) were treated with the
      Spence procedure, which alleviated symptoms in only 1. Six patients (25%)
      required cystectomy. CONCLUSIONS: In patients undergoing supravesical urinary
      diversion for benign disease in whom the bladder remains in situ the risks of
      complications related to the defunctionalized bladder are more than 50% and 25%
      of patients subsequently need cystectomy. These patients should be offered
      primary cystectomy at urinary diversion.

PMID- 16813906
TI  - Determining the importance of change in the overactive bladder questionnaire.
AB  - PURPOSE: The overactive bladder questionnaire assesses symptom bother and health
      related quality of life in patients with overactive bladder. It has been shown to
      be reliable, valid and responsive. We established the minimally important
      difference of the overactive bladder questionnaire. MATERIALS AND METHODS: Post
      hoc analyses from 2 clinical trials were performed. Distribution based, eg effect
      size, and anchor based analyses using perception of treatment benefit and
      clinical variables were used. RESULTS: The mean age of the 2 study populations
      was 58.8 and 58.7 years, respectively. Patients were predominantly female (51.8%
      and 75.1%) and white (83.9% and 87%, respectively). Half SD of the overactive
      bladder questionnaire symptom bother subscale was 9.1 to 9.3, and half SD of the
      overactive bladder questionnaire health related quality of life subscales
      (coping, concern, sleep and social interaction) was 9.8 to 13.2. Questionnaire
      subscales had moderate to large effect sizes with the largest effect sizes for
      symptom bother (-0.85 to -1.09). Anchor based analyses showed that significantly
      greater change scores were associated with greater patient perceived treatment
      benefit and satisfaction. The difference between change scores in patients
      perceiving no and little benefit was 7.4 to 16.5 for all questionnaire scales
      except social interaction with the majority greater than 10 points. Greater
      change scores were consistently associated with greater improvements in
      micturition diary variables. CONCLUSIONS: Multiple methodologies provide strong
      justification for the recommendation of a 10-point minimally important difference
      for all overactive bladder questionnaire subscales. This minimally important
      difference may be conservative for some subscales, although a uniform minimally
      important difference is recommended to facilitate interpretation of the
      overactive bladder questionnaire.

PMID- 16813908
TI  - What is a clinician to do-believe the patient or her urinary diary?
AB  - PURPOSE: We determined if patient recall of incontinence episodes correlates with
      urinary diary record. MATERIALS AND METHODS: Women with 1 or more urge
      incontinence episode per week completed 2, 7-day diaries, the Urinary Distress
      Inventory and Incontinence Impact Questionnaire, and responded to 2 recall
      questions. RESULTS: The median number of incontinence episodes participants
      recalled (6.5, 5) was higher than those recorded in the diary (1.9, 1.1) at both
      points. Incontinence episodes in 2, 7-day diaries correlated strongly (rho =
      0.921, p <0.005) while participant recall of incontinence episodes correlated
      weakly (rho = 0.309, p <0.059). When subjects reported being only slightly or not
      bothered by urge incontinence, recall and diary record correlated strongly (rho =
      0.812, p = 0.014). With increasing bother (moderate or great), recall and diary
      were not significantly correlated (rho = 0.528, p = 0.115). CONCLUSIONS: Women
      with urge incontinence either overestimate or under record incontinence episode
      frequency in the urinary diary. This effect is more pronounced in women who are
      more bothered by incontinence.

PMID- 16813910
TI  - Urgency is the core symptom of female overactive bladder syndrome, as
      demonstrated by a statistical analysis.
AB  - PURPOSE: We determined overactive bladder symptoms in combination with other
      lower urinary tract symptoms and illustrated their relationships using a
      statistical analysis. Furthermore, we also describe the potential contributory
      factors and adaptation strategies in patients that are associated with overactive
      bladder subtypes. MATERIALS AND METHODS: A total of 1,930 women with a mean age
      +/- SD of 46 +/- 15 years (range 15 to 91) with troubling lower urinary tract
      symptoms were successfully interviewed with a validated questionnaire at the
      urology and urogynecology clinics at 14 medical centers in Taiwan. The
      questionnaire was constructed to evaluate 6 lower urinary tract symptoms and 7
      adaptation strategies. A log linear statistical model and multiple logistic
      regression analysis were used to assess the associations among lower urinary
      tract symptoms and the potential overactive bladder contributory factors,
      respectively. RESULTS: No single or isolated symptom presented in patients with
      overactive bladder. Most patients reported a combination with other lower urinary
      tract symptoms. These female patients can be categorized into 3 groups, including
      1 is associated with dry symptoms (urgency, frequency and nocturia), 1 associated
      with wet symptoms (urgency, urge incontinence and mixed stress incontinence) and
      a small group that may have overactive bladder symptoms combined with voiding
      difficulty symptoms. in contrast to patients with dry overactive bladder (urgency
      associated with frequency and/or nocturia without urge incontinence), after
      multiple logistic regression analysis patients with wet overactive bladder
      (urgency with urge incontinence) had a greater average age and higher body mass
      index, and made more adaptation efforts (p <0.05). CONCLUSIONS: We used
      statistical analysis to determine and suggest that urgency is the core symptom of
      female overactive bladder syndrome and there are 3 distinctive overactive bladder
      subtypes, which differ in their symptom combinations. Different symptom
      combinations and patient characteristics affect female adaptation to overactive
      bladder syndrome.

PMID- 16813911
TI  - Therapeutic effect of multiple resiniferatoxin intravesical instillations in
      patients with refractory detrusor overactivity: a randomized, double-blind,
      placebo controlled study.
AB  - PURPOSE: Previous study has shown that multiple intravesical instillations of
      resiniferatoxin (Sigma) at 10 nM has therapeutic effects in patients with
      detrusor overactivity. To our knowledge the placebo effect of multiple
      instillations of low dose resiniferatoxin for neurogenic and nonneurogenic
      detrusor overactivity has not been investigated. In this randomized, double
      blind, placebo controlled study we evaluated the therapeutic effects of this
      resiniferatoxin treatment. MATERIALS AND METHODS: A total of 54 patients with
      detrusor overactivity refractory to anticholinergics were enrolled and randomly
      treated with 4 weekly intravesical instillations of 10 nM resiniferatoxin (26) or
      vehicle, consisting of 10% ethanol in normal saline, as the control group (28).
      The clinical effects of treatment on incontinence grade, incontinence episodes,
      general satisfaction, lower urinary tract symptoms and urodynamic parameters were
      assessed. RESULTS: Three months after completing the 4 intravesical treatments
      the resiniferatoxin treatment group had a significantly higher percent of
      patients with excellent and improved results compared to the control group (19.2%
      vs 7.1% and 42.3% vs 14.2%, respectively, each p < 0.001). Treatment remained
      effective at 6 months in 13 patients (50%) in the resiniferatoxin group but in
      only 3 (11%) in the control group (p < 0.001). Bladder capacity was significantly
      increased and symptom scores significantly improved 3 months after treatment in
      the resiniferatoxin group but not in the control group. CONCLUSIONS: Multiple
      intravesical instillations of 10 nM resiniferatoxin were effective for improving
      the incontinence grade in 62% of patients at 3 months, of whom 50% maintained a
      therapeutic effect 6 months after treatment. The therapeutic effect of
      resiniferatoxin was significantly superior to that of placebo.

PMID- 16813912
TI  - Comparison of the Q-tip test and voiding cystourethrogram to assess urethral
      hypermobility among women enrolled in a randomized clinical trial of surgery for
      stress urinary incontinence.
AB  - PURPOSE: We compared 2 measures of urethral hypermobility, the Q-tip test and
      voiding cystourethrogram, preoperatively in women recruited in 1 center
      participating in a multicenter randomized clinical trial comparing Burch
      colposuspension with autologous rectus fascia sling. MATERIALS AND METHODS:
      Following institutional review board approval, women with stress urinary
      incontinence and pelvic organ prolapse stage 2 or less underwent a standardized
      standing voiding cystourethrogram and a Q-tip test at a 45 degree angle reclining
      position preoperatively. Urethral angle at rest and straining were measured with
      a radiological ruler (voiding cystourethrogram) or goniometer (Q-tip) by 2
      different investigators blinded to each other findings. RESULTS: In 43 patients
      the mean urethral angle at rest and UAS were 20 degrees +/- 12 and 51 degrees +/-
      20, by voiding cystourethrogram compared to 16 degrees +/- 9 and 58 degrees +/-
      10 by Q-tip test, respectively. The mean angle difference (urethral angle with
      straining minus urethral angle at rest) was greater for the Q-tip test (42
      degrees +/- 9) than that for the voiding cystourethrogram test (32 degrees +/-
      17; p < 0.05). Fewer patients (14% by Q-tip, 28% by voiding cystourethrogram) had
      urethral hypermobility using the definition of urethral angle at rest greater
      than 30, while almost all patients (91% by voiding cystourethrogram, 100% by Q
      tip) had urethral hypermobility using the definition of urethral angle with
      straining greater than 30. However, using the definition of urethral angle with
      straining minus urethral angle at rest greater than 30, only 58% of patients had
      urethral hypermobility by voiding cystourethrogram compared to 98% by Q-tip.
      CONCLUSIONS: The voiding cystourethrogram and the Q-tip test measure urethral
      hypermobility differently. This may affect which patients are classified as
      having urethral hypermobility, and the choice of anti-incontinence surgery.

PMID- 16813914
TI  - High rate of vaginal erosions associated with the mentor ObTape.
AB  - PURPOSE: The transobturator tape method is a newer surgical technique for the
      treatment of stress urinary incontinence. Limited data exist related to
      complications with this approach or the types of mesh products used. We report
      our experience with vaginal erosions associated with the Mentor ObTape and
      American Medical Systems Monarc transobturator slings. MATERIALS AND METHODS:
      Beginning in December 2003 selected female patients with anatomic urinary
      incontinence were prospectively followed after placement of the Mentor ObTape.
      Beginning in January 2004 we also began using the American Medical Systems Monarc
      in similar patients. Patients were admitted overnight after surgery, discharged
      on oral antibiotics, and seen in the clinic at 6 weeks postoperatively. RESULTS:
      A total of 67 patients have undergone placement of the Mentor ObTape and 9 of
      those patients (13.4%) have had vaginal extrusions of the sling. Eight patients
      reported a history of persistent vaginal discharge. One patient presented
      initially to an outside facility with a left thigh abscess tracking to the left
      inguinal incision site. Each patient was taken back to the operating room for
      mesh removal. A total of 56 patients have undergone placement of the AMS Monarc
      and none have had any vaginal erosions. CONCLUSIONS: Our high rate of vaginal
      extrusion using the ObTape has led us to discontinue the use of this product in
      our institution. Continued followup of all of these patients will be of critical
      importance.

PMID- 16813916
TI  - Long-term results of robotic assisted laparoscopic sacrocolpopexy for the
      treatment of high grade vaginal vault prolapse.
AB  - PURPOSE: Transabdominal sacrocolpopexy is a definitive treatment option for
      vaginal vault prolapse with durable success rates. However, it is associated with
      increased morbidity compared with vaginal repairs. We describe a minimally
      invasive technique of vaginal vault prolapse repair and present our experience
      with a minimum of 1 year followup. MATERIALS AND METHODS: The surgical technique
      involves 5 laparoscopic ports: 3 for the da Vinci robot and 2 for the assistant.
      A polypropylene mesh is attached to the sacral promontory and vaginal apex using
      polytetrafluoroethylene sutures. The mesh material is then covered by peritoneum.
      Patient analysis focused on complications, urinary continence, patient
      satisfaction and morbidity with a minimum of 12 months followup. RESULTS: A total
      of 30 patients with post-hysterectomy vaginal vault prolapse underwent robotic
      assisted laparoscopic sacrocolpopexy at our institution and 21 have a minimum of
      12 months followup. Mean followup was 24 months (range 12 to 36) and mean age was
      67 years (range 47 to 83). Mean operative time was 3.1 hours (range 2.15 to
      4.75). All but 1 patient were discharged home on postoperative day 1 and the 1
      patient left on postoperative day 2. Recurrent grade 3 rectocele developed in 1
      patient, 1 had recurrent vault prolapse and 2 had vaginal extrusion of mesh. All
      patients were satisfied with outcome. CONCLUSIONS: The robotic assisted
      laparoscopic sacrocolpopexy is a minimally invasive technique for vaginal vault
      prolapse repair, combining the advantages of open sacrocolpopexy with the
      decreased morbidity of laparoscopy. We found a decreased hospital stay, low
      complication rates and high patient satisfaction with a minimum of 1 year
      followup.

PMID- 16813917
TI  - A clinical investigation of nocturnal polyuria in patients with nocturia: a
      diurnal variation in arginine vasopressin secretion and its relevance to mean
      blood pressure.
AB  - PURPOSE: Nocturia is a common lower urinary condition in the elderly population
      and nocturnal polyuria is recognized as a major factor responsible for nocturia.
      A functional change in osmotic or nonosmotic control regarding the water-salt
      balance with aging may contribute to nocturnal polyuria. This study evaluated
      plasma arginine vasopressin secretion function in symptomatic patients with
      nocturnal polyuria and the impact of mean blood pressure on nocturnal polyuria.
      MATERIALS AND METHODS: A total of 29 patients who had nocturnal polyuria with 3
      or more voids nightly and were screened with a 24-hour voiding diary were
      evaluated for their diurnal rhythm of arginine vasopressin secretion and osmotic
      response during a 5% hypertonic saline infusion test. Moreover, the relationships
      between the severity of nocturnal polyuria, ie the nocturnal polyuria index, or
      mean voided volume and mean blood pressure were assessed. RESULTS: Decreased
      nocturnal baseline arginine vasopressin according to plasma osmolality was found
      in 11 patients (38%) and the lack of a diurnal rhythm for arginine vasopressin
      secretion was observed in high proportion. A positive correlation between plasma
      arginine vasopressin and plasma osmolality was described with a linear regression
      line, expressed as arginine vasopressin = 0.27 (plasma osmolality - 285),
      resulting in a 2 to 3 mmol/l upward shift in the threshold of overall plasma
      arginine vasopressin secretion, although various osmotic sensitivities in
      arginine vasopressin secretion were observed in individuals. Mean voided volume
      increased during the night more than during the day (p <0.0001). A significant
      positive correlation of mean blood pressure with the mean daytime-to-nighttime
      single voided volume ratio and the nocturnal polyuria index was found (p = 0.0343
      and 0.0109, respectively). CONCLUSIONS: An abnormal diurnal variation in arginine
      vasopressin secretion is highly prevalent in nocturnal polyuria. Moreover, it is
      relevant to mean blood pressure or sympathetic tone, such that the effects of
      nonosmotic control seem clinically implicated. Particular emphasis has been
      applied to the importance of considering comprehensive assessments not only of
      arginine vasopressin secretion function, but also of the possible underlying
      cardiovascular condition or hypertension in the treatment modality of nocturnal
      polyuria.

PMID- 16813918
TI  - Visual analog scale questionnaire to assess quality of life specific to each
      symptom of the International Prostate Symptom Score.
AB  - PURPOSE: We assessed patient quality of life specific to each of the 7 items on
      the International Prostate Symptom Score, as evaluated with a novel visual analog
      scale questionnaire. MATERIALS AND METHODS: A total of 246 male patients with a
      chief complaint of lower urinary tract symptom were asked to complete the
      International Prostate Symptom Score and visual analog scale questionnaires to
      assess bother or satisfaction regarding patient quality of life specific to each
      of the 7 items on the International Prostate Symptom Score. RESULTS: An item with
      the maximum visual analog scale measure matched the chief complaint in 169
      patients (69%). In contrast, the chief complaint failed to match to an item with
      the most severe International Prostate Symptom Score in 104 patients (42%) (p =
      0.012). Multiple regression analysis to define the best predictor of
      International Prostate Symptom Score quality of life score of the 14 items,
      including International Prostate Symptom Score and visual analog scale, revealed
      that the best predictor was the visual analog scale measure for nocturia (p =
      0.0003), followed by visual analog scale measures for frequency (p = 0.0004) and
      incomplete emptying (p = 0.01). After alpha-blocker treatment improvement in the
      visual analog scale measure for the chief complaint correlated better with
      improvement in the International Prostate Symptom Score quality of life score
      than the change in International Prostate Symptom Score. The overall test-retest
      correlation for the visual analog scale questionnaire in 55 healthy elderly men
      and 44 patients with lower urinary tract symptoms was 0.772 and 0.742,
      respectively (p <0.00001). CONCLUSIONS: The novel visual analog scale measure of
      quality of life specific to each of the 7 items on the International Prostate
      Symptom Score has a significant impact on identifying the patient chief complaint
      as well as on patient specific quality of life. Our study supports the
      concomitant use of the International Prostate Symptom Score and visual analog
      scale questionnaires.

PMID- 16813919
TI  - Brain processing of audiovisual sexual stimuli inducing penile erection: a
      positron emission tomography study.
AB  - PURPOSE: Penile erection is dependent on commands from the central nervous
      system. Although basic studies of animals and neuroimaging studies of humans have
      been conducted to identify key brain regions associated with sexual arousal, to
      our knowledge no reliable studies of the first excitation phase of sexual arousal
      leading to penile erection have been reported. MATERIALS AND METHODS: We used
      H(2)(15)O-positron emission tomography to analyze regional cerebral blood flow
      just before penile erection in heterosexual volunteers. The subjects viewed 3
      different types of audiovisual materials-sexually explicit clips, nonsexual
      neutral clips and dynamic mosaic image control clips-presented in random order,
      and penile rigidity was monitored in real time with a RigiScan(R) Plus device.
      Positron emission tomography scanning was initiated simultaneously when each clip
      was started, and images obtained when the subjects showed appropriate penile
      response were analyzed and compared. RESULTS: The advanced audiovisual cortices
      and cerebellar vermis in the right hemisphere were activated for sexually
      explicit-dynamic mosaic image control clip contrast, and only the right middle
      frontal gyrus was activated for sexually explicit- nonsexual neutral clip
      contrast. Several primary visual and audio regions were activated for dynamic
      mosaic image control-sexually explicit clip contrast and nonsexual neutral
      sexually explicit clip contrast. CONCLUSIONS: We speculate that advanced
      audiovisual activity with imagination, not primary visual and audio activity,
      occurs when men experience sexual arousal inducing penile erection. Furthermore,
      the cerebellar vermis may be a key region for induction of penile erection in
      humans.

PMID- 16813920
TI  - Assessing urinary diversion experience in urologic residency programs-are we
      adequately training the next generation?
AB  - PURPOSE: Operative experience is important in developing surgical skills and
      technical competency. There is also emerging evidence directly linking increased
      surgical volume to patient outcomes. Accordingly, resident training should
      provide the framework for mastery of complex operations. We evaluated the current
      urological residency experience in performing adult urinary diversion. MATERIALS
      AND METHODS: The Accreditation Council for Graduate Medical Education-Residency
      Review for Urology Operative Log Reports were reviewed from 2000 to 2004 with an
      emphasis on urinary diversion experience. Resident logs were analyzed
      specifically for all procedures that included CPT codes for continent and
      incontinent diversions. The logs were compared by year of training and type of
      urinary diversion. RESULTS: Overall, the total number of urinary diversions
      performed by graduating residents from 4-year programs has increased from 2,259
      (2000 to 2001) to 4,017 (2003 to 2004). In addition, the mean and median number
      of urinary diversion cases among residents completing training have remained
      relatively constant. For graduating urology residents in 2003 to 2004, the mean
      (median) number of continent urinary diversion and incontinent urinary diversion
      cases were only 6.7 (3.0) and 9.5 (4), respectively. CONCLUSIONS: Current
      Accreditation Council for Graduate Medical Education data suggest the average
      urology resident has limited exposure to urinary diversion in general, and even
      less experience with more complex continent urinary diversion. These results
      suggest that many urology residency programs may not have sufficient volume to
      provide residents with a broad experience in urinary diversion, and alternative
      strategies to ensure proper training should be explored.

PMID- 16813921
TI  - Informed versus uninformed consent for prostate surgery: the value of electronic
      consents.
AB  - PURPOSE: We evaluated the documentation of informed consent for 2 common prostate
      operations using current, conventional, paper based consent forms. Based on the
      results of the review the conventional paper based consent system was replaced
      with a new, standardized electronic consent system. MATERIALS AND METHODS: We
      retrospectively reviewed the consent forms obtained for transurethral resection
      of the prostate and radical prostatectomy procedures during the 6-year period
      1995 to 2000 at Atlanta Veterans Affairs Medical Center. Analysis focused on the
      basic elements of informed consent, including a description of the proposed
      treatment, and the purpose, benefits, risks and alternatives. Based on these
      findings we standardized the procedure specific information contained in consent
      forms and stored it electronically in a central network accessible to all urology
      providers throughout the medical center. RESULTS: Of the 222 total procedures 204
      consent forms were available for review. Senior residents, junior residents and
      physician assistants obtained consent for 42.2%, 30.9% and 25.5% of procedures,
      respectively. Information on the purpose and benefits of treatment was missing in
      4.4% of cases and deficient in 22.6%. General or procedure specific risks were
      documented inconsistently in 0% to 96% of cases. Alternative treatment options
      were missing in 49% of the consent forms and they were significantly deficient in
      the remaining 51%. Prognosis and surgical risks were documented variably for each
      procedure. For example, in the radical prostatectomy group 79 patients (88.8%)
      had appropriate documentation regarding the potential for significant blood loss
      and yet only 23 (25.8%) had documented consent for blood transfusion. Following
      the implementation of a new standardized electronic consent program 96.1% of the
      patients surveyed preferred the new system. CONCLUSIONS: Conventional
      nonstandardized consent forms have significant deficiencies and errors. The new
      system of electronic informed consent is standardized, legible and
      understandable, and it assists providers in fully informing patients about the
      treatment, risks, benefits and alternative therapies, thereby supporting ethical
      and legal standards, and improving the quality of care. In our opinion
      standardized electronic informed consent should be the new standard of care.

PMID- 16813923
TI  - Enucleation for prepubertal leydig cell tumor.
AB  - PURPOSE: Leydig cell tumors in children are rare, comprising only 4% to 9% of all
      primary testis tumors in prepubertal males. Almost all of these boys present with
      isosexual precocious pseudopuberty associated with increased testosterone, low
      gonadotropin levels and a testis mass. We present our experience with testis
      sparing enucleation of Leydig cell tumor in prepubertal boys. MATERIALS AND
      METHODS: Two patients presented with isosexual precocious puberty at ages 6 and 9
      years. Each patient had a well circumscribed, painless testicular mass, increased
      serum testosterone (101 and 444 ng/dl [normal 0 to 25]), normal gonadotropins and
      negative alpha-fetoprotein levels. Both patients underwent successful enucleation
      of the testis mass following proper testis oncological surgical principles.
      RESULTS: Both patients had normalization of the serum testosterone following
      enucleation of the Leydig cell tumor. At 9 and 44 months of followup they have
      maintained normal ipsilateral testicular volume compared to the contralateral
      gonad, and 1 patient entered puberty spontaneously at 1 year postoperatively.
      Neither patient suffered any morbidity, and both have presumably benefited from
      preservation of the involved gonad with preserved testicular volume. CONCLUSIONS:
      Prepubertal boys with isosexual precocious pseudopuberty, an isolated testis
      mass, increased testosterone and low or normal gonadotropin levels can reliably
      be diagnosed with Leydig cell tumors. Based on the ability to establish the
      diagnosis preoperatively and the universal benign behavior of unilateral,
      prepubertal Leydig cell tumor, we believe these patients are best treated with
      testis sparing enucleation of the tumor. In view of the high likelihood that this
      tumor in prepubertal boys is benign, a transscrotal surgical approach should be
      considered.

PMID- 16813924
TI  - Treatment of renal stones in children: a comparison between percutaneous
      nephrolithotomy and shock wave lithotripsy.
AB  - PURPOSE: We compared the results of percutaneous nephrolithotomy and shock wave
      lithotripsy for the treatment of 1 to 2 cm renal stones in children. MATERIALS
      AND METHODS: The study included 166 children with renal stones 1 to 2 cm. A total
      of 75 patients (82 kidneys) were treated with percutaneous nephrolithotomy and 91
      (93 kidneys) were treated with shock wave lithotripsy. Mean followup was 31 +/-
      10 months (range 6 to 84). Both groups were compared regarding stone-free rate,
      re-treatment rate, complications and incidence of stone recurrence. RESULTS: Both
      groups were comparable regarding preoperative characteristics. Of the units
      treated with percutaneous nephrolithotomy 4 (4.9%) were associated with minor
      complications. Stone-free rate after a single session of percutaneous
      nephrolithotomy was 86.6% (71 units), and the remaining 11 kidneys with residual
      stones were successfully treated with repeat percutaneous nephrolithotomy in 7
      and shock wave lithotripsy in 4. Therefore, a total of 78 units (95%) were stone
      free after percutaneous nephrolithotomy monotherapy, and the overall stone-free
      rate at 3 months was 100%. Of the patients undergoing shock wave lithotripsy 1
      (1.1%) had development of steinstrasse and was successfully treated with
      ureteroscopy. The overall re-treatment rate after shock wave lithotripsy was 55%.
      A total of 79 units (84.9%) were stone-free after shock wave lithotripsy
      monotherapy, whereas 7 (7.5%) with no gross response to treatment were treated
      with percutaneous nephrolithotomy and 7 with insignificant stones less than 4 mm
      were followed. Therefore, the overall stone-free rate at 3 months was 92.5%. The
      differences in stone-free rates and re-treatment rates significantly favored
      percutaneous nephrolithotomy, while the incidence of complications and stone
      recurrence at last followup were not significantly different between the groups.
      CONCLUSIONS: For treatment of 1 to 2 cm renal stones in children percutaneous
      nephrolithotomy is better than shock wave lithotripsy, yielding higher stone-free
      and lower re-treatment rates.

PMID- 16813925
TI  - Foreskin preservation in penile surgery.
AB  - PURPOSE: Most hypospadias repairs performed in the United States involve the
      removal of any foreskin that is not used in the repair, resulting in a
      circumcised penis. Occasionally, the wishes of the parents or the child are for
      the final appearance to be that of a normal uncircumcised penis. We report our
      collective experience from 4 institutions in the reconstruction of the foreskin
      during penile surgery. MATERIALS AND METHODS: A total of 58 patients underwent
      penile surgery with reconstruction of the foreskin during a 6-year period. Of the
      patients 49 underwent hypospadias repair, 8 underwent phalloplasty for chordee
      correction without hypospadias and 1 underwent reconstruction of the foreskin for
      a dorsal hood without hypospadias or chordee. Of the 49 hypospadias repairs 46
      were distal, 2 mid shaft and 1 proximal shaft. The technique for foreskin
      reconstruction consisted of a multilayered reapproximation of the lateral margins
      of the dorsal hood after completion of the urethroplasty and glanuloplasty.
      RESULTS: Among 49 hypospadias repairs 2 patients had dehiscence of the
      reconstructed foreskin, with development of a urethral fistula in 1. Of the 58
      total patients undergoing penile surgery 56 had retractable foreskin, of whom 4
      required postoperative steroid application. Three patients/parents requested a
      secondary circumcision, 2 for an unacceptable cosmetic result and 1 based on
      personal preference. CONCLUSIONS: Foreskin reconstruction in association with
      penile surgery can be performed safely and with a low complication rate in
      appropriately selected patients. Cases with a higher risk of complications
      include those involving more proximal hypospadias and those requiring complete
      degloving of the penile shaft. Of the reconstructions resulting in phimosis most
      can be salvaged with the application of steroids.

PMID- 16813926
TI  - A favorable experience with rotational flap techniques for fashioning the Firlit
      preputial collar.
AB  - PURPOSE: The Firlit collar technique for the approximation of the divergent inner
      leaf of the prepuce in operations to repair hypospadias and its variants are
      generally easily conceptualized and executed. However, in some cases the
      divergence is so great at the level of the corona that a simple approximation
      cannot be performed. Therefore, 2 techniques are described that facilitate
      completion of the Firlit collar in these instances. MATERIALS AND METHODS: A
      total of 101 boys 6 to 101 months old (mean 18.9) underwent formation of a Firlit
      collar between July 2003 and July 2004. Among the patients 69 had coronal or
      glanular hypospadias, 17 had a penile or a more proximal meatus and 15 had only a
      hooded prepuce. In 5 patients the divergence of the inner leaf of the prepuce
      precluded a simple midline approximation of the 2 halves. Two techniques of
      forming rotational flaps of the inner leaf were used to complete construction of
      the Firlit preputial collar. RESULTS: The techniques were used as described in 5
      repairs, with excellent cosmetic results. CONCLUSIONS: Two rotational flap
      techniques for the repair of the widely divergent inner leaf of the prepuce
      associated with hypospadias and its variants are described and recommended for
      their simplicity and uniformly good results.

PMID- 16813927
TI  - Smooth muscle cell apoptosis and defective neural development in congenital
      ureteropelvic junction obstruction.
AB  - PURPOSE: We assessed the smooth muscle cell apoptosis along with changes in
      cellular and extracellular components of the ureteropelvic junction in 23
      patients with unilateral obstruction and compared them with 25 autopsies from
      ureteropelvic junction regions of age matched cadavers. MATERIALS AND METHODS:
      Tissue specimens obtained from pyeloplasty were divided into 3 sections-renal
      pelvis above the obstruction, obstructed ureteropelvic junction and ureter below
      the obstructed region. For the control group the normal ureteropelvic junctions
      of age matched infants were autopsied. In paraffin embedded sections we
      determined myocyte apoptosis index (using TUNEL assay), and the amount of
      muscular components and nerve terminals (using image analysis techniques after
      immunohistochemical staining). The collagen and elastin fibers were specifically
      stained for evaluation of changes in extracellular matrix. RESULTS: Smooth muscle
      cell apoptosis index was significantly increased at the site of ureteropelvic
      junction obstruction (5.68 +/- 0.18) compared to normal autopsied ureteropelvic
      junctions (3.60 +/- 0.11) and 2 other sections of obstructed ureteropelvic
      junction complex (renal pelvis 4.73 +/- 0.16, and ureter 3.97 +/- 0.16). The
      number of nerve terminals and the percentage of muscular component were
      significantly lower at the obstructed segments of affected patients compared to
      normal ureteropelvic junctions. Meanwhile, collagen fibers formed a significantly
      higher proportion of ureteral wall at the site of obstruction. Interestingly,
      there was negative correlation between myocyte apoptosis indices and number of
      nerve endings as well as amount of muscular components at the site of
      ureteropelvic junction obstruction. However, positive correlations were found
      between smooth muscle cell apoptosis and the percentage of collagen and elastin
      fibers. CONCLUSIONS: Our findings suggest an important role for myocyte apoptosis
      and defective neural development in the pathogenesis of congenital ureteropelvic
      junction obstruction that could pave the road for the emergence of new
      therapeutic modalities.

PMID- 16813930
TI  - The magnitude of fetal renal pelvic dilatation can identify obstructive postnatal
      hydronephrosis, and direct postnatal evaluation and management.
AB  - PURPOSE: Up to 1% of prenatal ultrasounds will detect fetal renal pelvic
      dilatation. We sought to evaluate and determine whether fetal renal pelvic
      measurements may appropriately direct prenatal counseling and postnatal
      evaluation and management. MATERIALS AND METHODS: We performed a retrospective
      analysis of prospectively collected measurements of anteroposterior renal pelvic
      dilatation obtained at a single fetal maternal medicine center between 1990 and
      2003. Fetuses with renal pelvic dilatation 4 mm or greater at less than 33 weeks
      of gestation, or 7 mm or greater at more than 33 weeks of gestation were
      evaluated postnatally at a single pediatric urology center. Infants with renal
      pelvic dilatation were evaluated with ultrasound, voiding cystourethrograms and
      renal scintigraphy. Renal obstruction was the main outcome measure assessed.
      Obstruction was defined as the need for surgery and was not based on the renal
      scan drainage time. Indications for surgery included declining function and
      increasing hydronephrosis. RESULTS: There were 257 neonates with prenatally
      detected renal pelvic dilatation. A mean maximum prenatal renal pelvic dilatation
      of 11.8 mm was seen in 195 patients with nonobstructive dilatation. In the 62
      patients with obstruction there was a nearly 2-fold increase in the mean renal
      pelvic dilatation (22.3 mm), which was statistically significant. Receiver
      operating characteristic analysis revealed that when 15 mm renal pelvic
      dilatation is used as a threshold it correctly discriminates obstruction in at
      least 80% of fetuses with a sensitivity of 73% and a specificity of 82%.
      CONCLUSIONS: The magnitude of fetal renal pelvic dilatation is predictive of
      obstruction. Our results suggest that 15 mm renal pelvic dilatation represents a
      significant threshold. Receiver operating characteristic analysis provides a
      useful guide for prenatal counseling and may help to direct the postnatal
      evaluation.

PMID- 16813932
TI  - Steroid receptors and mammalian penile development: an unexpected role for
      progesterone receptor?
AB  - PURPOSE: We investigated the role of steroid receptors in normal and abnormal
      genital tubercle development in males and females. We hypothesized that
      progesterone receptor expression might be involved in abnormal development in
      both sexes. MATERIALS AND METHODS: We examined the effects of medroxyprogesterone
      acetate on steroid receptor mRNA expression and assessed the involvement of
      androgen receptor in the action of medroxyprogesterone acetate on genital
      tubercle development using androgen receptor deficient (Tfm) mice. RESULTS:
      Quantitative reverse transcriptase polymerase chain reaction and morphological
      results demonstrated a pattern of virilized females and feminized males in
      medroxyprogesterone acetate exposed embryos. Progesterone receptor was the only
      steroid receptor examined that did not differ between medroxyprogesterone acetate
      treated males and vehicle treated females. At the morphological level in utero
      exposure to medroxyprogesterone acetate from gestational days 12 to 17 feminized
      male genital tubercles, producing a more proximal urethral opening. Female
      fetuses exposed for the same period exhibited virilized genitalia, with a more
      distal urethral opening. We also exposed Tfm mice to medroxyprogesterone acetate
      to assess the role of androgen receptor in the activity of medroxyprogesterone
      acetate. These medroxyprogesterone acetate exposed mice did not differ
      morphologically from vehicle treated Tfm mice, indicating that
      medroxyprogesterone acetate requires androgen receptor to elicit genital tubercle
      abnormalities. CONCLUSIONS: The increase of progesterone receptor mRNA expression
      in males and the decrease in females as a result of exposure to
      medroxyprogesterone acetate, which also causes urethral abnormalities in both
      sexes, suggests a previously unidentified role for progesterone receptor,
      possibly interacting with androgen receptor, in anomalous genital tubercle
      development.

PMID- 16813933
TI  - The incidence of bilateral cryptorchidism is increased and the fertility
      potential is reduced in sons born to mothers who have smoked during pregnancy.
AB  - PURPOSE: Recent studies have demonstrated a high prevalence of cryptorchidism,
      decreasing semen quality and increasing incidence of testicular cancer. These
      changes seem to be interrelated, and may be symptoms of a common underlying
      entity with foundations in fetal life. We investigated the influence of maternal
      smoking on fertility status in offspring cryptorchidism. MATERIALS AND METHODS:
      We prospectively studied consecutive patients presenting to the pediatric surgery
      department between 1996 and 2005. A total of 157 boys 1 to 5.9 years old
      underwent surgery for cryptorchidism with simultaneous testicular biopsy, and
      exhibited well preserved testicular parenchyma. Only white patients with Danish
      speaking mothers who had reported pregnancy history including smoking habits
      during pregnancy and history of the offspring were included. The patients had
      cryptorchidism only and none received hormonal treatment before surgery. The
      number of spermatogonia and gonocytes per tubule cross-section was assessed and
      compared to normal values from autopsy material. RESULTS: The group of boys with
      cryptorchidism whose mothers had smoked heavily during pregnancy (ie more than 10
      cigarettes daily throughout the pregnancy) had a significantly increased risk of
      bilateral cryptorchidism (52%, or 11 of 21 patients), and a decreased number of
      spermatogonia and gonocytes per tubule cross-section, which was absolute (0.097
      [0 to 0.75]) and age related (14% [0% to 198%] of normal for age) compared to
      boys whose mothers did not smoke (20%, or 22 of 112 patients, 0.140 [0 to 2.14]
      and 37% [0% to 563%] of normal for age, p <0.01, p <0.05 and p <0.05,
      respectively). CONCLUSIONS: A close relationship between maternal smoking during
      pregnancy and adverse trends in offspring reproductive health in relation to
      cryptorchidism was observed.

PMID- 16813934
TI  - The impact of attention deficit hyperactivity disorders on brainstem dysfunction
      in nocturnal enuresis.
AB  - PURPOSE: In a specialized university setting the prevalence of attention deficit
      hyperactivity disorder in general and particularly the inattentive subtype
      attention deficit hyperactivity disorder of the predominantly inattentive subtype
      is highly increased. We replicated previous research findings that enuresis is
      associated with a brainstem deficit and investigated the impact of attention
      deficit hyperactivity disorder on this brainstem deficit in enuresis. MATERIALS
      AND METHODS: Electromyography recorded startle eye blink modification with and
      without attentional modulation was used to measure brainstem functioning in 158
      children between 6 and 12 years old. Performance in 3 enuresis groups, including
      children with enuresis, enuresis plus attention deficit hyperactivity disorder of
      the predominantly inattentive subtype and enuresis plus attention deficit
      hyperactivity disorder combined, respectively, was compared with that in normally
      developing controls and in children with attention deficit hyperactivity disorder
      subtypes without enuresis. RESULTS: In an automatic attentional task the enuresis
      groups showed decreased brainstem inhibition compared to that in the control and
      attention deficit hyperactivity disorder groups (p <0.006). In a controlled
      attentional task children with and without enuresis who had attention deficit
      hyperactivity disorder of the predominantly inattentive subtype were unable to
      show attentional modulation in all age groups (p <0.02). CONCLUSIONS: Startle eye
      blink modification research reveals a brainstem inhibition deficit in children
      with enuresis, which could explain why they are unable to remain dry at night.
      When additional attention is allocated to specific trials in the task, children
      with attention deficit hyperactivity disorder of the predominantly inattentive
      subtype fail to optimize sensory gating. With respect to enuresis, this could
      result in an identification problem of bladder signals, leading to an inadequate
      or absent arousal effect in attention deficit hyperactivity disorder of the
      predominantly inattentive subtype.

PMID- 16813935
TI  - Desmopressin resistant nocturnal polyuria secondary to increased nocturnal
      osmotic excretion.
AB  - PURPOSE: We investigated the role of increased solute excretion in children with
      desmopressin resistant nocturnal enuresis and nocturnal polyuria. MATERIALS AND
      METHODS: A total of 42 children with monosymptomatic nocturnal enuresis and
      significant nocturnal polyuria with high nocturnal urinary osmolality (more than
      850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration
      profile was obtained with measurement of urine volume, osmolality, osmotic
      excretion and creatinine. The control group consisted of 100 children without
      enuresis. RESULTS: Based on osmotic excretion patients were classified into 3
      groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to
      a high renal osmotic load. This was probably diet related since 11 of these 12
      patients were obese. Group 2 had increased osmotic excretion in the evening and
      night, probably due to a high renal osmotic load caused by the diet
      characteristics of the evening meal. Group 3 had deficient osmotic excretion
      during the day, secondary to extremely low fluid intake to compensate for small
      bladder capacity. CONCLUSIONS: Nocturnal polyuria with high urinary osmolality in
      our patients with desmopressin resistant monosymptomatic nocturnal enuresis is
      related to abnormal increased osmotic excretion. This may be explained by their
      fluid and diet habits, eg daytime fluid restriction, and high protein and salt
      intake.

PMID- 16813936
TI  - Desmopressin toxicity due to prolonged half-life in 18 patients with nocturnal
      enuresis.
AB  - PURPOSE: Desmopressin has been used extensively for primary nocturnal enuresis
      and it is associated with a low incidence of adverse effects. The only reported
      serious side effect is seizure or altered levels of consciousness resulting from
      water intoxication, which has been reported for the nasal spray. We describe 18
      children with clinical symptoms of water intoxication due to the prolonged
      bioactivity of desmopressin nasal spray. MATERIALS AND METHODS: We evaluated 18
      patients with clinical suspicion of prolonged desmopressin bioactivity during
      treatment with intranasal desmopressin for primary nocturnal enuresis. The
      control group consisted of 50 children with primary nocturnal enuresis and proven
      nocturnal polyuria who were treated with the same desmopressin regimen. RESULTS:
      All patients had prolonged maximal urinary concentration capacity and delayed
      restoration of daytime diluting capacity (p <0.01). Of the patients 15 had the
      characteristic clinical symptoms of water intoxication with vomiting, headache,
      decreased consciousness and hyponatremia. We suspect that these symptoms are
      secondary to prolonged desmopressin bioactivity. CONCLUSIONS: Prolonged
      desmopressin bioactivity may increase the risk of water intoxication.

PMID- 16813939
TI  - Bladder reservoir function in children with monosymptomatic nocturnal enuresis
      and healthy controls.
AB  - PURPOSE: We investigated bladder reservoir function in children with
      monosymptomatic nocturnal enuresis and in healthy controls. MATERIALS AND
      METHODS: A total of 18 children with monosymptomatic nocturnal enuresis and 119
      controls who were 7 to 13 years old were recruited. Children completed frequency
      volume charts and measurements of nocturnal urine production. Mean diuresis in
      the period preceding each voiding was calculated. Those with enuresis were
      grouped according to bladder capacity and hospitalized for 4 nights, including a
      baseline night and 3 with an oral water load. Enuresis volumes and post-void
      residual volume were estimated, allowing the calculation of bladder volume at the
      time of enuresis. RESULTS: Nine children with monosymptomatic nocturnal enuresis
      were characterized as having normal bladder capacity and 9 had decreased bladder
      capacity. We found large intra-individual variability in daytime voided volume in
      all 3 groups of participants. Children with enuresis and small bladder capacity
      generally voided with volumes close to maximal voided volume. A total of 93
      enuresis episodes were recorded. Large intra-individual variability was seen in
      bladder volume at enuresis and it was lower than maximal voided volume in more
      than 50% of episodes. Variability in bladder volume at enuresis was greatest in
      the patient group with decreased bladder capacity. We found a significant
      correlation between diuresis and bladder capacity in all groups during the day
      and night. CONCLUSIONS: There is a great intra-individual diurnal variability in
      voided volume in children with enuresis and in healthy children. Enuresis seems
      to occur at bladder volumes that are smaller and larger than the maximal voided
      volume obtained from voiding charts.

PMID- 16813940
TI  - The role of bladder capacity in antidiuretic and anticholinergic treatment for
      nocturnal enuresis.
AB  - PURPOSE: We evaluated combination treatment with desmopressin and oxybutynin in
      patients with enuresis who did not respond to desmopressin monotherapy.
      Furthermore, we compared 2 methods of estimating bladder capacity and evaluated
      the ability of these methods to predict the response to desmopressin and
      oxybutynin. MATERIALS AND METHODS: A total of 60 children with a mean age +/- SD
      of 10.6 +/- 3.0 years who had monosymptomatic nocturnal enuresis completed the
      study. After a 2-week observation period maximal voided volume during free access
      to fluid intake was determined by a 2-day frequency-volume chart and maximal
      voided volume after water load was determined on a separate day. Patients then
      received 20 mug desmopressin intranasally at bedtime during 2 weeks. In
      nonresponders to desmopressin with less than a 50% decrease in wet nights 5 mg
      oxybutynin twice daily was added for another 2 weeks. RESULTS: Of the patients 41
      (68%) showed more than 50% decrease in wet nights during the 2-week desmopressin
      treatment period (4.6 +/- 1.6 to 0.7 +/- 0.8, p <0.001). In desmopressin
      nonresponders combined treatment with desmopressin and oxybutynin resulted in a
      further decrease in wet nights (4.0 +/- 1.2 to 1.7 +/- 1.4, p <0.001). Maximal
      voided volume during free access to fluid intake was significantly higher in
      desmopressin responders than in nonresponders (244 +/- 111 vs 160 +/- 65 ml, p
      <0.001). In contrast, maximal voided volume after water load was not
      significantly different between desmopressin responders and nonresponders.
      CONCLUSIONS: The study indicates a role for oxybutynin in combination with
      desmopressin in children who are not responding to desmopressin monotherapy.
      Maximal voided volume during free access to fluid intake is a clinically useful
      predictor of the response to desmopressin but not to oxybutynin.

PMID- 16813943
TI  - Urinary calcium excretion in healthy children and children with primary
      monosymptomatic nocturnal enuresis.
AB  - PURPOSE: We investigated the role of urinary Ca excretion in monosymptomatic
      nocturnal enuresis, and defined normality and intra-individual variability in Ca
      excretion in healthy children. MATERIALS AND METHODS: We included 46 Danish
      children with desmopressin resistant nocturnal enuresis and 96 healthy controls.
      We performed fractional urine collections at home during 2 days in controls or
      during hospitalization in children with enuresis. Urine volume, osmolality, and
      Ca and creatinine measurements were performed and Ca-to-creatinine ratios were
      calculated and compared between groups. Based on nocturnal urine output children
      with enuresis were characterized as having polyuria (nocturnal urine volume
      greater than 130% of expected bladder capacity) or not having polyuria. RESULTS:
      We did not find any differences in controls compared with children with enuresis
      who did not and did have nocturnal polyuria in daytime Ca excretion (mean +/- SE
      0.121 +/- 0.012, 0.078 +/- 0.014 and 0.095 +/- 0.020 mg/mg creatinine), nighttime
      Ca excretion (0.115 +/- 0.011, 0.092 +/- 0.019 and 0.139 +/- 0.029 mg/mg
      creatinine) or 24-hour Ca excretion (0.118 +/- 0.011, 0.083 +/- 0.014 and 0.106
      +/- 0.020 mg/mg creatinine, respectively). Urinary Ca excretion was not
      influenced by patient age, sex or body weight and, furthermore, we did not find
      evidence of diurnal variation. However, we observed considerable intra-individual
      variability in diurnal, nocturnal and total 24-hour urinary Ca-to-creatinine
      ratios. CONCLUSIONS: These observations contradict several previous reports and
      speculations on a role of Ca in the pathogenesis of nocturnal enuresis.

PMID- 16813944
TI  - Circadian variation of angiotensin II and aldosterone in nocturnal enuresis:
      relationship to arterial blood pressure and urine output.
AB  - PURPOSE: We investigated the circadian rhythm of solute excretion and regulating
      hormones as well as blood pressure in patients with monosymptomatic nocturnal
      enuresis. MATERIALS AND METHODS: We included 15 patients with a mean age +/- SE
      of 13.4 +/- 0.9 years who had monosymptomatic nocturnal enuresis with at least 3
      wet nights weekly and a control group of 10 healthy children with a similar age
      and sex distribution. During inpatient circadian studies urine was collected
      during 6 periods and blood was drawn at 7 time points during 24 hours. Heart rate
      and blood pressure was recorded with an ambulatory blood pressure monitor every
      30 to 60 minutes. RESULTS: The total patient group excreted a significantly
      larger nocturnal urine volume than controls (p <0.01). Five patients had marked
      nocturnal polyuria (nocturnal urine volume greater than the mean in the control
      group +2 SD), whereas urine output in the remaining patients without polyuria
      were similar to controls. Nocturnal polyuria was caused mainly by increased
      nocturnal solute excretion, especially Na. Serum aldosterone and plasma
      angiotensin II showed a marked circadian rhythm in normal children with a
      nocturnal increase concomitant with a significant decrease in mean arterial blood
      pressure during sleep. In contrast, the group of patients with nocturnal polyuria
      showed a lack of circadian rhythm in all excretion variables as well as an
      attenuated rhythm in plasma angiotensin II and mean arterial blood pressure.
      Interestingly this group had normal circadian rhythms of the circadian rhythm
      markers plasma cortisol and heart rate. CONCLUSIONS: The study suggests that an
      abnormally large nocturnal excretion of Na caused by selectively attenuated
      circadian rhythms of Na regulating hormones might be an important pathogenic
      factor in monosymptomatic nocturnal enuresis.

PMID- 16813945
TI  - Small cell carcinoma of the bladder.

PMID- 16813946
TI  - Carcinoma of the pancreas presenting with gross hematuria: diagnosis by
      multiphasic multidetector computerized tomography.

PMID- 16813947
TI  - Precise characterization of renal parenchymal response to single and multiple
      cryoablation probes.
AB  - PURPOSE: We characterized the size and shape of the ablated area, and the
      surrounding indeterminate zone associated with renal cryolesions produced by
      single and multiple cryoablation probe configurations in a porcine model.
      MATERIALS AND METHODS: Laparoscopic cryoablation, consisting of 2, 10-minute
      double freeze cycles followed by a 3-minute active thaw, was performed in 18
      pigs. Three groups of 6 pigs each were studied, including a single IceRod, 3 rods
      arranged in a triangular configuration 2 cm apart from each other and 4 rods
      arranged in a quadratic configuration 2 cm from each other. Cryoablated kidneys
      were harvested after 14 days for histopathological evaluation. RESULTS: The mean
      diameter of the area of complete ablation produced by a 1, 3 and 4 rod
      configuration 1 cm from the tip of the rod was 2.0, 4.4 and 4.9 cm, respectively.
      Cryolesions were elliptical with 1 cryoablation probe and in the 3 and 4 rod
      configurations they conformed to triangular and quadratic cross-sectional shapes,
      respectively. In the zone, ablation a single small focus of peri-arteriolar renal
      cell viability was noted less than 1 mm from the edge of the cryolesion in 1 of
      the 18 cryolesions. Otherwise no viable renal cells were detected. CONCLUSIONS:
      Multirod configurations can be used with templates to space cryoablation probes 2
      cm apart from each other with reliable and complete ablation overlap between the
      rods. However, around larger blood vessels the ice ball must be extended to a
      larger margin to ensure complete tissue ablation.

PMID- 16813948
TI  - Schedule dependent efficacy of gefitinib and docetaxel for bladder cancer.
AB  - PURPOSE: We determined the sequence specific efficacy of gefitinib and docetaxel
      treatment for bladder cancer. This combination was selected because it is
      currently under study in a phase II clinical trial. MATERIALS AND METHODS: In
      vitro antiproliferative effects of gefitinib, docetaxel and a combination were
      determined in the 4 bladder cancer cell lines 253J B-V, UM-UC-3, KU-7 and UM-UC
      13 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell
      cycle analysis was analyzed using flow cytometry and propidium iodide labeling.
      Epidermal growth factor receptor downstream signaling was assessed by Western
      blot analysis. In vivo nude mice were injected subcutaneously with 253J B-V cells
      and treated with placebo, gefitinib, docetaxel, docetaxel followed by gefitinib
      or gefitinib followed by docetaxel. Tumor kinetics were established. RESULTS:
      Gefitinib demonstrated antiproliferative effect against 253J B-V cells (50%
      inhibitory concentration less than 0.5 muM) but no apoptotic effect in vitro,
      whereas docetaxel demonstrated antiproliferative and apoptotic effects. When
      gefitinib and docetaxel were combined, gefitinib enhanced the apoptotic and
      antiproliferative effects of docetaxel only when gefitinib was administered
      following docetaxel pretreatment. Apoptosis increased from 45% to 66%. In vivo
      there were significant differences in tumor weight in mice treated with
      combination therapy vs gefitinib or docetaxel alone. Importantly improved
      efficacy was observed when docetaxel was followed by gefitinib administration
      compared with gefitinib followed by docetaxel (mean tumor weight 42 vs 93 mg, p =
      0.022). Sequence specific efficacy was not observed in UM-UC-3, UM-UC-13 and KU-7
      cells, which are resistant to gefitinib. CONCLUSIONS: Docetaxel followed by
      gefitinib demonstrated sequence specific efficacy against gefitinib sensitive
      bladder cancer compared with gefitinib followed by docetaxel or either drug
      alone. Accordingly gefitinib administration concurrently or after chemotherapy
      might be the sequence of choice and it should be considered for future clinical
      trials.

PMID- 16813949
TI  - The E-cadherin -160 C/A polymorphism and prostate cancer risk in white and black
      American men.
AB  - PURPOSE: We have previously reported that a C/A single nucleotide polymorphism at
      position -160 of the human E-cadherin gene promoter affects E-cadherin
      transcription. Although this single nucleotide polymorphism is associated with a
      number of human cancers, including prostate cancer, it is not known whether it
      has a role in race related prostate cancer. We hypothesized that allelic
      variation at this site may be associated with racial differences in the incidence
      and severity of prostate cancer. MATERIALS AND METHODS: We analyzed the genotypes
      of this single nucleotide polymorphism in a total of 135 prostate cancer samples
      from 86 white and 49 black American men, and in 237 samples from normal healthy
      controls, including 120 white and 117 black men, using the polymerase chain
      reaction-restriction fragment length polymorphism technique. RESULTS: Of normal
      controls black men had a higher frequency of the A allele and CA genotype than
      white men (26.5 and 39.3 vs 22.5 and 28.3, respectively). In white men A allele
      frequency was significantly higher in those with prostate cancer than in controls
      (p <0.05). White men carrying the A allele and AA genotype were at 1.99-fold (95%
      CI 1.29 to 3.08) and 3.04-fold (95% CI 1.26 to 7.32) higher risk for prostate
      cancer than carriers of the C allele and CC genotype. However, in black men the A
      allele was more frequent in controls than in patients with cancer and it was
      associated with a 2.4-fold decrease in prostate cancer risk (95% CI 0.22 to 0.81)
      compared to the C allele. CONCLUSIONS: The A allele of the E-cadherin -160 single
      nucleotide polymorphism represents a prostate cancer risk factor in white but not
      in black men.

PMID- 16813950
TI  - Transient receptor potential vanilloid receptor subtype 1 in painful bladder
      syndrome and its correlation with pain.
AB  - PURPOSE: Painful bladder syndrome is a chronic, debilitating bladder
      hypersensitivity disorder characterized by urinary frequency, urgency and bladder
      pain without an identifiable cause. Recent advances in understanding the
      molecular basis of hypersensitivity provide an opportunity to advance the
      understanding of and treatment for painful bladder syndrome. We studied the heat
      and capsaicin receptor transient receptor potential vanilloid receptor subtype 1
      in the bladder in patients with painful bladder syndrome and their relationship
      to pain symptoms. MATERIALS AND METHODS: Bladder biopsies were obtained from 20
      characterized subjects with painful bladder syndrome and 25 with asymptomatic
      microscopic hematuria as controls. Specimens were immunostained using specific
      antibodies to transient receptor potential vanilloid receptor subtype 1 and
      neurofilaments as a structural maker. Nerve fiber and urothelial staining were
      quantified with computerized image analysis. The results of immunohistochemistry
      were correlated with the pain score. RESULTS: There was a marked increase in
      suburothelial nerve fibers expressing transient receptor potential vanilloid
      receptor subtype 1 in painful bladder syndrome in comparison with that in
      controls (p <0.0001). The ratio of transient receptor potential vanilloid
      receptor subtype 1 fibers to neurofilaments was also significantly increased in
      painful bladder syndrome, suggesting over expression of transient receptor
      potential vanilloid receptor subtype 1 (p <0.0001). When all specimens studied
      were included, the pain score correlated significantly with the relative nerve
      fiber density of transient receptor potential vanilloid receptor subtype 1 in the
      suburothelium (r = 0.6862, p = 0.0002) as well as the ratio of transient receptor
      potential vanilloid receptor subtype 1 fibers to neurofilaments (r = 0.5554, p =
      0.004). Urothelial transient receptor potential vanilloid receptor subtype 1
      showed a tendency toward an increase in the painful bladder syndrome group but it
      did not achieve statistical significance. No correlation was found between
      transient receptor potential vanilloid receptor subtype 1 immunoreactivity of
      urothelium or neurofilament fibers and the pain score. CONCLUSIONS: This study
      shows increased transient receptor potential vanilloid receptor subtype 1 in
      nerve fibers of the bladder in painful bladder syndrome and a correlation of the
      pain score with the relative density of transient receptor potential vanilloid
      receptor subtype 1 nerve fibers. Transient receptor potential vanilloid receptor
      subtype 1 may have a role in the pathophysiology of painful bladder syndrome and
      it is a potential target for novel therapeutic agents.

PMID- 16813951
TI  - Transvesical endoscopic peritoneoscopy: a novel 5 mm port for intra-abdominal
      scarless surgery.
AB  - PURPOSE: Recently various groups reported successful attempts to perform intra
      abdominal surgery through a transgastric pathway. We assessed the feasibility and
      safety of a novel transvesical endoscopic approach to the peritoneal cavity
      through a 5 mm port in a porcine model. MATERIALS AND METHODS: Transvesical
      endoscopic peritoneoscopy was performed in 8 anesthetized female pigs, including
      3 nonsurvival and 5 survival animals. Under cystoscopic guidance a vesical hole
      was created on the ventral bladder wall with an open-ended ureteral catheter. An
      over tube with a luminal diameter of 5.5 mm was placed in the peritoneal cavity,
      guided by a 0.035-inch guidewire. In all animals we performed peritoneoscopy of
      the entire abdomen as well as liver biopsy and falciform ligament section. A
      vesical catheter was placed for 4 days in all survival animals, which were
      sacrificed by day 15 postoperatively. RESULTS: After a learning curve in the
      first 3 nonsurvival animals the creation of a vesical hole and placement of the
      over tube were performed without complication in all survival animals. In these
      animals we easily introduced an EndoEYEtrade mark into the peritoneal cavity,
      which provided a view of all intra-abdominal viscera, as well as a 9.8Fr
      ureteroscope, which allowed simple surgical procedures without complications. In
      survival experiments all pigs recovered. Necropsy examination revealed complete
      healing of the vesical hole and no signs of infection or adhesions into the
      peritoneal cavity. CONCLUSIONS: Transvesical endoscopic peritoneoscopy was
      technically feasible and it could be safely performed in a porcine model. This
      study provides encouragement for additional preclinical studies of transvesical
      surgery with or without combinations with other natural orifices approaches to
      design new intra-abdominal scarless procedures in what seems to be third
      generation surgery.

PMID- 16813952
TI  - Angiotensin receptor blockade decreases fibrosis and fibroblast expression in a
      rat model of unilateral ureteral obstruction.
AB  - PURPOSE: Unilateral ureteral obstruction is characterized by histopathological
      changes including interstitial fibrosis, fibroblast specific protein expression,
      tubular atrophy and apoptosis, and macrophage infiltration. Angiotensin II has
      been implicated in some of these changes. We examined the effect of angiotensin
      blockade on markers of renal injury, including fibroblast specific protein
      expression, fibrosis, apoptosis and macrophage infiltration. We used losartan, an
      angiotensin II antagonist, in a unilateral ureteral obstruction model and studied
      animals 3 weeks after unilateral ureteral obstruction, a time at which renal
      damage is well established. MATERIALS AND METHODS: Rats underwent unilateral
      ureteral obstruction and were given either drinking water or losartan for 21
      days. Kidneys were harvested and examined for fibrosis (trichrome and the Sircol
      assay for collagen), apoptosis (TUNEL), and fibroblast specific protein
      expression and macrophage infiltration (immunohistochemistry). RESULTS:
      Unilateral ureteral obstruction was found to induce fibrosis, apoptosis,
      fibroblast expression and macrophage in the obstructed kidney. Losartan
      significantly decreased apoptosis and macrophage infiltration in the obstructed
      kidney. It also decreased fibrosis, as measured by either trichrome staining
      assessed by a pathologist, the Sircol assay for collagen or fibroblast specific
      protein expression. However, approximately 50% of the changes were not affected
      by the current treatment, suggesting that other factors contribute to renal
      damage in unilateral ureteral obstruction. CONCLUSIONS: We observed the direct
      contribution of angiotensin II to both apoptotic and cellular transition
      processes (epithelial mesenchymal transition) and fibrosis in unilateral ureteral
      obstruction. Because these processes are active not only in unilateral ureteral
      obstruction, but also in other renal diseases, the value of angiotensin II
      blockade as an important part of the antifibrotic armamentarium has been
      confirmed.

PMID- 16813953
TI  - Epithelial architectural destruction is necessary for bone marrow derived cell
      contribution to regenerating prostate epithelium.
AB  - PURPOSE: Using various nonphysiological tissue injury/repair models numerous
      studies have demonstrated the capacity of bone marrow derived cells to contribute
      to the repopulation of epithelial tissues following damage. To investigate
      whether this phenomenon might also occur during periods of physiological tissue
      degeneration/regeneration we compared the ability of bone marrow derived cells to
      rejuvenate the prostate gland in mice that were castrated and then later treated
      with dihydrotestosterone vs mice with prostate epithelium that had been damaged
      by lytic virus infection. MATERIALS AND METHODS: Using allogenic bone marrow
      grafts from female donor transgenic mice expressing green fluorescent protein
      transplanted into lethally irradiated males we were able to assess the
      contributions of bone marrow derived cells to recovery of the prostatic
      epithelium in 2 distinct systems, including 1) surgical castration followed 1
      week later by dihydrotestosterone replacement and 2) intraprostatic viral
      injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone
      marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-
      >C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with
      green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent
      protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-
      >C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate
      tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days
      following intraprostatic viral injection. Prostate tissue immunofluorescence was
      performed with antibodies against the epithelial marker cytokeratin 5/8, the
      hematopoietic marker CD45 and green fluorescent protein. RESULTS: Mice that
      sustained prostate injury from vaccinia virus infection with concomitant severe
      inflammation and glandular disruption showed evidence of bone marrow derived cell
      reconstitution of prostate epithelium, that is approximately 4% of all green
      fluorescent protein positive cells in the epithelial compartment 14 days after
      injury expressed cytokeratin 5/8, similar to the proportion of green fluorescent
      protein positive cells in the prostate that no longer expressed the hematopoietic
      marker CD45. When prostatic degeneration/regeneration was triggered by androgen
      deprivation and reintroduction, no green fluorescent protein positive prostate
      epithelial cells were detected. CONCLUSIONS: These findings are consistent with a
      requirement for inflammation associated architectural destruction for the bone
      marrow derived cell contribution to the regeneration of prostate epithelium.

PMID- 16813954
TI  - Periurethral injection of sustained release basic fibroblast growth factor
      improves sphincteric contractility of the rat urethra denervated by botulinum-a
      toxin.
AB  - PURPOSE: We evaluated the effects of sustained release basic fibroblast growth
      factor injection in rat urethra denervated by botulinum-A toxin (Wako Life
      Science, Osaka, Japan). MATERIALS AND METHODS: A total of 30 female Sprague
      Dawley rats underwent periurethral injection of 10 U botulinum-A toxin to induce
      chemical denervation of the urethral sphincter. Leak point pressure in the waking
      state was determined and a significant decrease in leak point pressure vs that in
      control rats was confirmed (mean +/- SD 58.7 +/- 6.2 vs 120.7 +/- 13.0 cm H(2)O,
      p <0.0001). Two weeks later 0, 50 and 200 microg basic fibroblast growth factor
      incorporating 200 microl gelatin hydrogels in 10 rats each were injected into the
      urethral sphincter, enabling sustained release of basic fibroblast growth factor
      for 2 weeks. Four weeks later injection leak point pressure measurement and
      histological evaluation of the urethra were performed. RESULTS: Leak point
      pressure in rats with 50 and 200 microg basic fibroblast growth factor injection
      was significantly higher than in rats with the 0 microg injection (82.7 +/- 9.0
      vs 95.1 +/- 6.2 and 119.3 +/- 8.1 cm H(2)O, p = 0.0021 and <0.0001,
      respectively). Maximum cross-sectional area of the urethral smooth muscle layer
      in the 50 and 200 microg groups significantly increased compared with that in the
      urethra in the 0 micro group, which was considered 100% (114.1% +/- 15.8% and
      132.5% +/- 13.4%, p = 0.029 and <0.0001, respectively). Similarly the cross
      sectional area of the striated sphincter in the 50 and 200 microg groups was
      greater than the 100% in the 0 microg group (112.3% +/- 15.6% and 124.3% +/-
      14.1%, p = 0.069 and 0.0007, respectively). Vascular density in the urethral peri
      atrophic zone in the 50 and 200 microg groups was significantly higher than in
      the 0 microg group (p = 0.027 and <0.0001, respectively). CONCLUSIONS: Sustained
      release basic fibroblast growth factor injection in the chemically denervated
      urethral sphincter facilitates regeneration of the urethral muscles and improves
      sphincteric contractility. Endoscopic periurethral injection of basic fibroblast
      growth factor incorporating gelatin hydrogels may be an attractive therapy for
      stress urinary incontinence.

PMID- 16813955
TI  - The effect of FK1706 on erectile function following bilateral cavernous nerve
      crush injury in a rat model.
AB  - PURPOSE: We investigated the neurotrophic effect of FK1706 on erectile recovery
      following bilateral cavernous nerve crush injury in a rat model. MATERIALS AND
      METHODS: A total of 28 male Sprague-Dawley rats were randomly divided into 4
      equal groups. Seven animals underwent sham operation and subcutaneous vehicle
      injection, whereas 21 underwent bilateral cavernous nerve crush injury followed
      by vehicle injection alone, or by low (0.1 mg/kg) or high (1.0 mg/kg) dose FK1706
      treatment. Injections were continued 5 days weekly for 8 weeks. Erectile function
      was then assessed by cavernous nerve electrostimulation and penile tissue was
      evaluated immunohistochemically. RESULTS: No erectile dysfunction was identified
      in the sham treated group (mean maximal intracavernous pressure +/- SEM 106.8 +/-
      6.4 cm H(2)O), whereas nerve injury significantly decreased ICP to 17.9 +/- 7.0
      cm H(2)O. FK1706 facilitated neural and erectile recovery in a concentration
      dependent manner with a mean ICP in the high dose FK treatment group of 80.1 +/-
      7.8 cm H(2)O compared with 44.1 +/- 12.9 cm H(2)O in the low dose group. Similar
      stepwise findings were observed using mean area under the curve data. Sham
      treated animals showed regular axon sizes and shapes with homogenous GAP-43 and
      neurofilament staining, whereas injured axons showed irregular shapes, sizes and
      staining patterns. FK1706 treatment restored axon shape and staining patterns.
      Injury significantly decreased nicotinamide adenine dinucleotide phosphate
      staining and FK1706 treatment showed a nonsignificant trend toward increased
      staining. CONCLUSIONS: Bilateral cavernous nerve crush causes reproducible
      erectile dysfunction, consistent with prior experiments. High dose subcutaneous
      FK1706 therapy promotes significant neuroregeneration and erectile function
      recovery.

PMID- 16813956
TI  - In vivo detection of apoptotic cells in the testis using fluorescence labeled
      annexin V in a mouse model of testicular torsion.
AB  - PURPOSE: It is well established that experimental testicular torsion induces germ
      cell specific apoptosis. Annexin V (BD Pharmingentrade mark) binds
      phosphatidylserine that becomes exposed on the cell membrane in apoptotic cells.
      In vivo detection of apoptotic cells with fluorescently labeled annexin V is an
      emerging technique that we evaluated for detecting apoptotic germ cells in a
      mouse model of testicular torsion. MATERIALS AND METHODS: Annexin V labeled with
      an indocyanine fluorophore (bisfunctional succinimidyl ester of cyanine 5.5)
      (Amersham, Little Chalfont, United Kingdom) was injected intravenously in mice 18
      hours after the repair of unilateral 720-degree testicular torsion for 2 hours.
      Serial fluorescence images were obtained 21, 24, 28 and 42 hours after torsion
      repair. Relative fluorophore localization was visualized in vivo using an optical
      small animal imaging system mounted with a filter in near infrared light. Average
      fluorescence intensity in torsed and sham testes was quantified in images of
      testes in situ exposed through an abdominal incision and in ex vivo testes.
      RESULTS: A significant increase in fluorescence intensity was found in images of
      torsed vs sham operated testes. This was seen in ex vivo, exposed and in vivo
      testes (215%, 250% and 161%, respectively, p <0.05). Bisfunctional succinimidyl
      ester of cyanine 5.5 conjugated to dehydrogenase, a protein with a size similar
      to that of annexin V, was used to assess for capillary leakage. It was also more
      localized to the torsed testis relative to its contralateral sham control whether
      exposed or ex vivo (174% and 176%, respectively). CONCLUSIONS: To our knowledge
      this study demonstrates for the first time the possibility of in vivo near
      infrared fluorescence imaging of apoptotic germ cells after testicular torsion in
      mice. It shows important confounding factors that must be considered as this new
      imaging technique is developed for detecting apoptotic cells in vivo in testes or
      in any other organ.

PMID- 16813957
TI  - Re: cyclosporine A and pentosan polysulfate sodium for the treatment of
      interstitial cystitis: a randomized comparative study.

PMID- 16813958
TI  - Re: wound complications after hand assisted laparoscopic surgery.

PMID- 16813960
TI  - Re: prenatal ultrasound has led to earlier detection and repair of ureteropelvic
      junction obstruction.

PMID- 16813962
TI  - Re: prevalence and risk factors for female sexual dysfunction in Turkish women.

PMID- 16813963
TI  - Re: sexual dysfunction in women with hyperprolactinemia: a pilot study report.

PMID- 16813965
TI  - Re: no-needle jet anesthetic technique for no-scalpel vasectomy.

PMID- 16813966
TI  - Re: multi-institutional validation study of neural networks to predict duration
      of stay after laparoscopic radical/simple or partial nephrectomy.

PMID- 16813967
TI  - Re: testicular fixation following torsion of the spermatic cord--does it
      guarantee prevention of recurrent torsion events?

PMID- 16813969
TI  - Systematic review: intravenous Ibuprofen in preterm newborns.
AB  - Ibuprofen, a nonsteroidal antiinflammatory drug, widely used as antipyretic,
      antiinflammatory, and analgesic agent and for therapy of arthritis, exerts a dose
      dependent constriction of the ductus arteriosus in newborn lambs. Two intravenous
      preparations, namely ibuprofen lysine and ibuprofen-THAM, have been studied in
      preterm newborns with patent ductus arteriosus. Clinical trials have compared IV
      ibuprofen to placebo, or to indomethacin. Pharmacodynamic effects of this drug
      before and after its administration have also been evaluated. Compared with
      placebo, IV ibuprofen effectively closed PDA with minimal effect on renal
      function. One study using intravenous ibuprofen-THAM showed decreased renal
      function and increased risk of NEC and PPHN. Compared with indomethacin, IV
      ibuprofen lysine exerted similar efficacy (75% to 93% closure). However,
      indomethacin increased abnormal renal function and decreased mesenteric and
      cerebral blood flow and bio-energetics. Two clinical trials showed that ibuprofen
      did not reduce the incidence of intraventricular hemorrhage compared with
      placebo. The drug has prolonged elimination (plasma half-life = ca 23 hours),
      suggesting that once daily dosing is appropriate. Dose finding studies indicate
      that a starting dose of 10 mg/kg followed by 5 mg/kg/d for 2 more days provides
      optimal efficacy with the least adverse effects. Neonatal data on ibuprofen and
      indomethacin indicate that, on the first day of life when IVH prevention is
      desired, indomethacin and not ibuprofen should be used since ibuprofen has no
      effect on IVH risk. On or after the second day of postnatal life, when early or
      therapeutic PDA closure is needed, ibuprofen and not indomethacin is probably the
      first choice due to its better adverse event profile.

PMID- 16813970
TI  - Pathogenesis of bronchopulmonary dysplasia: the role of interleukin 1beta in the
      regulation of inflammation-mediated pulmonary retinoic acid pathways in
      transgenic mice.
AB  - BACKGROUND: Pulmonary inflammation, increased production of the inflammatory
      cytokine interleukin-1beta (IL-1beta), and vitamin A deficiency are risk factors
      for the development of bronchopulmonary dysplasia (BPD) in premature infants. To
      determine the mechanisms by which IL-1beta influences lung development, we have
      generated transgenic mice in which human IL-1beta is expressed in the lung
      epithelium with a doxycycline-inducible system controlled by the Clara cell
      secretory protein promoter. Perinatal IL-1beta production in these mice causes a
      phenotype that is strikingly similar to BPD. Pulmonary pathology in the mice
      shows inflammation, lack of alveolar septation, and impaired vascular development
      of the lung, similar to the histological characteristics of BPD. Retinoic acid
      (RA), one of the most biologically active derivatives of vitamin A, increases
      septation. Proteins involved in mediating the cellular responses to RA include
      the cellular retinoic acid binding proteins CRABP-I and CRABP-II and the nuclear
      retinoic acid receptors RAR-alpha, RAR-beta, and RAR-gamma. OBJECTIVE: To test
      the hypothesis that IL-1beta inhibits the expression of proteins involved in
      mediating the cellular response to RA. METHODS: The mRNA expression of CRABP-I,
      CRABP-II, RAR-alpha1, RAR-beta2, RAR-beta4, and RAR-gamma2 was studied with real
      time RT-PCR on gestational day 18, and postnatal days 0, 1, 5, and 7 in IL-1beta
      expressing mice and their control littermates. In addition, immunohistochemistry
      for CRABP-I was performed. RESULTS: IL-1beta decreased the mRNA expression and
      protein production of CRABP-I as well as the mRNA expression of RAR-gamma2. In
      contrast, no differences between IL-1beta-expressing and control mice were
      detected in the expression of CRABP-II, RAR-alpha1, RAR-beta2, or RAR-beta4.
      CONCLUSION: The present study demonstrates for the first time a link between
      inflammation and the retinoic acid pathway. Inhibition of CRABP-I and RAR-gamma2
      expression may be one mechanism by which inflammation prevents alveolar
      septation. The therapeutic potential of RA in promoting septation in the setting
      of perinatal lung inflammation deserves further investigation.

PMID- 16813971
TI  - Hypercapnia- and trans-arachidonic acid-induced retinal microvascular
      degeneration: implications in the genesis of retinopathy of prematurity.
AB  - High oxygen tension is a major factor in the genesis of retinopathy of
      prematurity (ROP). However, clinical and experimental evidence suggests a
      significant role for high carbon dioxide (CO(2)) tension as well. Along these
      lines, although ischemia is often considered to be synonymous with an oxygen
      deficit, it is also associated with a concomitant local elevation of CO(2) that
      can lead to impaired developmental and ischemic neovascularization. The
      mechanisms by which hypercapnia induces retinal microvascular degeneration, a
      critical step which precedes the subsequent proliferative preretinal
      neovascularization, are not known. Nitrative stress has an important role in
      microvascular degeneration leading to ischemia in conditions such as ROP.
      Hypercapnia is a facilitator of nitration in vitro. We hereby present evidence
      that prolonged exposure to CO(2) impairs developmental retinal neovascularization
      through a mechanism involving increased endothelial nitric oxide synthase and
      induction of a nitrative stress; effects of hypercapnia are independent of its
      hyperaemic effects. Moreover, we demonstrate that an in vivo nitrative stress
      associated with retinal vasoobliteration results in nitration of arachidonic
      acids into trans-arachidonic acids (TAAs), which can act as mediators of
      nitrative stress by causing microvascular degeneration by inducing expression of
      the antiangiogenic factor thrombospondin-1. These recent findings establish a
      previously unexplored means by which hypercapnia hinders efficient
      neovascularization and provide new insight into the molecular mechanisms of
      nitrative stress on microvascular injury involving TAA, and suggest new
      therapeutic avenues in the management of nitrative stress disorders such as in
      ischemic retinopathies (of prematurity and of diabetes) and encephalopathies.

PMID- 16813972
TI  - Photoprotection of parenteral nutrition enhances advancement of minimal enteral
      nutrition in preterm infants.
AB  - BACKGROUND: Light exposure of TPN generates peroxides which induce
      vasoconstriction. Mesenteric vasoconstriction may affect feeding tolerance. Since
      photo-protection of TPN decreases peroxide generation, we hypothesized that
      shielding TPN from light may improve the establishment of minimal enteral
      nutrition in preterm infants. METHODS: Infants were randomized to TPN being light
      exposed (LE) or protected (LP) from birth. Feeding volumes were monitored through
      7 days of life in those initiated on minimal enteral nutrition (MEN). Comparisons
      between LP and LE were performed by ANOVA. RESULTS: Daily increments and
      cumulative volumes of enteral feeds (mL/kg birth weight/d) during the first week
      of life were significantly higher in LP (n = 18) than LE (n = 19). CONCLUSION:
      Photo-protection of parenteral nutrition enhances advancement of MEN in preterm
      infants. Further research is needed to substantiate these findings and determine
      whether this confers long-term nutritional advantages.

PMID- 16813973
TI  - Pre-wallerian degeneration in the neonatal brain following perinatal cerebral
      hypoxia-ischemia demonstrated with MRI.
AB  - AIM: Pre-Wallerian degeneration was studied in term and near-term neonates with
      hypoxic-ischemic brain injury, and related to neurodevelopmental outcome.
      SUBJECTS: Thirty-nine surviving patients with hypoxic-ischemic encephalopathy or
      seizures and MRI-documented brain abnormalities were included. Patients were
      grouped according to the MRI findings: group 1 (n = 23), ischemic stroke or
      watershed infarcts; group 2 (n = 8), lesions of the basal ganglia; group 3 (n =
      8), predominantly white matter lesions. METHODS: Cranial MRI, including diffusion
      weighted MRI, was performed between 1 and 10 days after birth. ADC maps were
      created, and presence or absence of pre-Wallerian degeneration in the cerebral
      peduncles was assessed. RESULTS: Of the 15 neonates with pre-Wallerian
      degeneration, 14 had permanent abnormalities of motor development, whereas 1 had
      a transient asymmetry. Six neonates with a poor outcome had no pre-Wallerian
      degeneration, which may be contributed to the timing of the MRI in 2. Eighteen
      neonates had no pre-Wallerian degeneration and a normal motor development.
      CONCLUSION: Pre-Wallerian degeneration of the cerebral peduncles in neonates with
      hypoxia-ischemia is almost invariably associated with a poor motor development.
      In neonates with abnormalities of the basal ganglia or white matter and a poor
      outcome, pre-Wallerian degeneration is less common than in neonates with stroke
      or watershed infarcts and a poor motor outcome.

PMID- 16813974
TI  - Short- and long-term consequences of hypotension in ELBW infants.
AB  - BACKGROUND: Hypotension affects close to half of all ELBW infants, yet an
      agreement on its definition is still lacking. Despite the fact that neonatal
      hypotension may be a risk factor for neurologic impairment, there is a paucity of
      data on the impact of low blood pressure (BP) in extremely low birth weight
      (ELBW) infants weighing below 1000 g on neuro-developmental outcome. OBJECTIVES:
      Explore the relationship between blood pressure in the first 72 hours of life,
      perinatal factors, morbidity, and mortality in ELBW infants. Compare neuro
      sensory outcome in ELBW infants with and without symptomatic hypotension.
      METHODS: We reviewed the outcome for all 156 infants with a birth weight <1000 g
      admitted to the neonatal intensive care unit covering the time period 1998 to
      1999. Infants who received fluid pushes and/or pressors during the first 72 hours
      of life in an attempt to increase blood pressure were regarded as "symptomatic"
      or "treated infants"; the others were designated "non-treated infants." Follow-up
      at 20 months corrected age included neurologic status, Bayley motor/mental
      evaluation, plus tests of vision and hearing. Statistical analysis was by SPSS
      11.0. Univariate and multivariate analyses were conducted to determine
      morbidities associated with symptomatic hypotension. RESULTS: A total of 59
      infants (mean BW 714 +/- 154 g; GA 24.9 +/- 1.7 weeks) required BP support; 97
      infants (mean BW 768 +/- 141 g; GA 26.1 +/- 1.9 weeks) received no BP support.
      The groups had similar race, gender, delivery mode, and maternal socioeconomic
      status. Thirty-five (22%) infants died, including 20 who received BP support.
      There were more infants with severe IVH (grade III/IV), 19% versus 2%, and the
      mortality was greater, 34% versus 16%, in those infants who received BP support.
      Of the 121 survivors, 110 (91%) had complete follow-up evaluations. Multivariate
      analysis controlling for SES and neonatal morbidity revealed that symptomatic
      hypotension is associated with delayed motor development (-6.0; SE 3.1) and
      hearing loss (O.R. 8.9; CI 0.92-86.3). CONCLUSIONS: Symptomatic hypotension in
      ELBW infants in the first 72 hours of life is associated with significant short
      term and long-term morbidity. Infants with symptomatic hypotension are more
      likely to have delayed motor development, hearing loss, and death.

PMID- 16813975
TI  - Neonatal lung and airway injury: a role for neurotrophins.
AB  - Maintenance of patency in distal airways is essential for gas exchange in
      neonatal life, and its disruption may have long-lasting effects on respiratory
      function. However, neural mechanisms that regulate caliber of intrapulmonary
      airways during early postnatal life, and their disruption by hyperoxic exposure,
      have not been well characterized. We have previously shown that cholinergically
      mediated airway contractile responses in rat pups are upregulated after hyperoxic
      exposure, and that increased expression of neuropeptides, such as substance P,
      may be contributory. More recently, we have documented impairment of neurally
      mediated airway relaxation in response to hyperoxic stress associated with loss
      of nitric oxide and prostaglandin-induced airway relaxation as well as inhibition
      of long chain myosin phosphatase. Our most recent data demonstrate significantly
      enhanced expression of the neurotrophin, brain-derived neurotrophic factor (BDNF)
      and its high affinity specific tyrosine kinase B (TrkB) receptor in hyperoxia
      exposed airway smooth muscle. The existence of a BDNF-TrkB receptor autocrine and
      paracrine loops in the airways provides a basis for understanding local
      regulatory mechanisms of airway homeostasis. A mechanistic role for BDNF-TrkB
      signaling in hyperoxia-induced airway hyperreactivity in early postnatal life
      could serve to modulate both afferent and efferent neural pathways that result in
      enhanced contractile responses of immature airways exposed to hyperoxic stress.
      Greater insight into these neural pathways may lead to future preventive
      strategies for preterm infants surviving neonatal intensive care and developing
      chronic lung disease.

PMID- 16813977
TI  - Antimicrobial resistance in gram-positive bacteria.
AB  - Gram-positive bacteria are common causes of bloodstream and other infections in
      hospitalized patients in the United States, and the percentage of nosocomial
      bloodstream infections caused by antibiotic-resistant gram-positive bacteria is
      increasing. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin
      resistant enterococci (VRE) are of particular concern. In the United States,
      approximately 60% of staphylococcal infections in the intensive care unit are now
      caused by MRSA, and percentages continue to rise. Outbreaks of hospital-acquired
      MRSA (HA-MRSA) are typically the result of clonal spread by MRSA being
      transferred from patient to patient, frequently using healthcare personnel as
      intermediaries. HA-MRSA strains are generally multidrug resistant. Vancomycin is
      the standard treatment for serious MRSA infections, but a few cases of vancomycin
      resistant S aureus (VRSA) have recently emerged in the United States. Community
      acquired MRSA (CA-MRSA) is also increasing. Soft tissue infections are the most
      frequent presentations of CA-MRSA, but life-threatening invasive infections occur
      as well, including necrotizing pneumonia. The mechanisms of methicillin
      resistance are the same for CA-MRSA and HA-MRSA, but susceptibilities to non-a
      lactam antibiotics often differ. CA-MRSA exhibits broader antibiotic
      susceptibility than does HA-MRSA. The proportion of enterococci resistant to
      vancomycin continues to rise in the hospital setting, with the overwhelming
      majority of infections due to Enterococcus faecium. Clonal spread of VRE has been
      documented, but polyclonal outbreaks associated with antimicrobial use are also
      common. The relations between antibiotic use and VRE colonization are complex and
      related to the antienterococcal activity, biliary excretion, and antianaerobic
      activity of the antibiotic. Recent results show a decline in invasive
      pneumococcal disease (IPD) since the introduction of 7-valent pneumococcal
      conjugate vaccine, and suggest that, where available, vaccines may be useful in
      the battle to slow the spread of resistant gram-positive cocci.

PMID- 16813978
TI  - Resistance in gram-negative bacteria: Enterobacteriaceae.
AB  - The emergence and spread of resistance in Enterobacteriaceae are complicating the
      treatment of serious nosocomial infections and threatening to create species
      resistant to all currently available agents. Approximately 20% of Klebsiella
      pneumoniae infections and 31% of Enterobacter spp infections in intensive care
      units in the United States now involve strains not susceptible to third
      generation cephalosporins. Such resistance in K pneumoniae to third-generation
      cephalosporins is typically caused by the acquisition of plasmids containing
      genes that encode for extended-spectrum beta-lactamases (ESBLs), and these
      plasmids often carry other resistance genes as well. ESBL-producing K pneumoniae
      and Escherichia coli are now relatively common in healthcare settings and often
      exhibit multidrug resistance. ESBL-producing Enterobacteriaceae have now emerged
      in the community as well. Salmonella and other Enterobacteriaceae that cause
      gastroenteritis may also be ESBL producers, which is of relevance when children
      require treatment for invasive infections. Resistance of Enterobacter spp to
      third-generation cephalosporins is most typically caused by overproduction of
      AmpC beta-lactamases, and treatment with third-generation cephalosporins may
      select for AmpC-overproducing mutants. Some Enterobacter cloacae strains are now
      ESBL and AmpC producers, conferring resistance to both third- and fourth
      generation cephalosporins. Quinolone resistance in Enterobacteriaceae is usually
      the result of chromosomal mutations leading to alterations in target enzymes or
      drug accumulation. More recently, however, plasmid-mediated quinolone resistance
      has been reported in K pneumoniae and E coli, associated with acquisition of the
      qnr gene. The vast majority of Enterobacteriaceae, including ESBL producers,
      remain susceptible to carbapenems, and these agents are considered preferred
      empiric therapy for serious Enterobacteriaceae infections. Carbapenem resistance,
      although rare, appears to be increasing. Particularly troublesome is the
      emergence of KPC-type carbapenemases in New York City. Better antibiotic
      stewardship and infection control are needed to prevent further spread of ESBLs
      and other forms of resistance in Enterobacteriaceae throughout the world.

PMID- 16813979
TI  - Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the
      maximum.
AB  - Nonfermenting gram-negative bacteria pose a particular difficulty for the
      healthcare community because they represent the problem of multidrug resistance
      to the maximum. Important members of the group in the United States include
      Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia,
      and Burkholderia cepacia. These organisms are niche pathogens that primarily
      cause opportunistic healthcare-associated infections in patients who are
      critically ill or immunocompromised. Multidrug resistance is common and
      increasing among gram-negative nonfermenters, and a number of strains have now
      been identified that exhibit resistance to essentially all commonly used
      antibiotics, including antipseudomonal penicillins and cephalosporins,
      aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole,
      and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly
      consistent activity against multidrug-resistant strains of P aeruginosa,
      Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia
      are not susceptible to polymyxins, and systemic polymyxins carry the risk of
      nephrotoxicity for all patients treated with these agents, the elderly in
      particular. A variety of resistance mechanisms have been identified in P
      aeruginosa and other gram-negative nonfermenters, including enzyme production,
      overexpression of efflux pumps, porin deficiencies, and target-site alterations.
      Multiple resistance genes frequently coexist in the same organism. Multidrug
      resistance in gram-negative nonfermenters makes treatment of infections caused by
      these pathogens both difficult and expensive. Improved methods for susceptibility
      testing are needed when dealing with these organisms, including emerging strains
      expressing metallo-beta-lactamases. Improved antibiotic stewardship and infection
      control measures will be needed to prevent or slow the emergence and spread of
      multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare
      setting.

PMID- 16813980
TI  - Mechanisms of antimicrobial resistance in bacteria.
AB  - The treatment of bacterial infections is increasingly complicated by the ability
      of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents
      are often categorized according to their principal mechanism of action.
      Mechanisms include interference with cell wall synthesis (eg, beta-lactams and
      glycopeptide agents), inhibition of protein synthesis (macrolides and
      tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and
      rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and
      disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria
      may be intrinsically resistant to > or =1 class of antimicrobial agents, or may
      acquire resistance by de novo mutation or via the acquisition of resistance genes
      from other organisms. Acquired resistance genes may enable a bacterium to produce
      enzymes that destroy the antibacterial drug, to express efflux systems that
      prevent the drug from reaching its intracellular target, to modify the drug's
      target site, or to produce an alternative metabolic pathway that bypasses the
      action of the drug. Acquisition of new genetic material by antimicrobial
      susceptible bacteria from resistant strains of bacteria may occur through
      conjugation, transformation, or transduction, with transposons often facilitating
      the incorporation of the multiple resistance genes into the host's genome or
      plasmids. Use of antibacterial agents creates selective pressure for the
      emergence of resistant strains. Herein 3 case histories-one involving Escherichia
      coli resistance to third-generation cephalosporins, another focusing on the
      emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing
      multidrug resistance in Pseudomonas aeruginosa-are reviewed to illustrate the
      varied ways in which resistant bacteria develop.

PMID- 16813981
TI  - Pharmacodynamics: relation to antimicrobial resistance.
AB  - Antibiotic pharmacodynamics (PD) describes the impact of an antimicrobial agent
      on a target pathogen and is based on the drug's pharmacokinetics (PK) and
      microbiologic activity toward that pathogen, together with the pathogen's
      susceptibility to the drug. Patient or host factors play an important role in
      antibiotic PD by affecting drug PK and patient susceptibility to infection. The 3
      PD parameters commonly used to predict antibiotic efficacy are (1) the ratio of
      maximum serum concentration to the minimum inhibitory concentration (MIC)
      (Cmax/MIC); (2) the ratio of the area under the plasma concentration versus time
      curve (AUC) versus MIC (AUC/MIC) and (3) the duration of the dosing interval that
      plasma concentrations exceed the MIC (T>MIC). The Cmax/MIC ratio has been shown
      to predict aminoglycoside efficacy, AUC/MIC best describes fluoroquinolone,
      glycopeptide, and ketolide efficacy, and T>MIC best describes the efficacy of
      beta-lactams and macrolides. Traditionally, PK and PD (PK/PD) parameters have
      been used to predict antibiotic efficacy, but there is now increasing interest in
      trying to use PK/PD parameters to minimize development of resistance. With
      respect to fluoroquinolone resistance, the "mutant selection window" hypothesis
      has been developed to describe how drug exposures below the mutant prevention
      concentration may create conditions for the selection of resistant bacterial
      strains. The AUC/MIC ratio has also been used to describe fluoroquinolone drug
      exposures associated with either increased or decreased risk of resistance
      emergence. The accessory gene regulator (agr) locus in Staphylococcus aureus-and
      particularly agr group II-has been associated with reduced susceptibility or
      resistance of S aureus to vancomycin. Recent experiments suggest that the AUC/MIC
      ratio may be used to identify vancomycin exposures associated with emergence of
      resistance in S aureus. More generally, AUC/MIC ratios may be additive, and
      combination therapies may represent 1 approach to lowering the emergence rate of
      bacterial resistance associated with antibiotic therapy. But, further work needs
      to be done before this conclusion can be verified.

PMID- 16813982
TI  - Managing methicillin-resistant staphylococci: a paradigm for preventing
      nosocomial transmission of resistant organisms.
AB  - Multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus
      (MRSA), are endemic in healthcare settings in the United States and many other
      countries of the world. Nosocomial transmission of MRSA serves as a source of
      hospital outbreaks, and recent reports of vancomycin-resistant S aureus strains
      in the United States emphasize the need for better control of MRSA and other
      resistant bacteria within healthcare settings. Colonization with S aureus or MRSA
      is relatively common in both healthy and hospitalized individuals, most often
      involves the anterior nares, and is frequently asymptomatic. Colonization
      increases risk of infection. Patient-to-patient transmission of MRSA within
      healthcare settings primarily occurs via carriage on the hands of healthcare
      workers. The Society for Healthcare Epidemiology of America (SHEA) has developed
      guidelines for the prevention of transmission of MRSA and vancomycin-resistant
      enterococci within healthcare settings, and chief among the recommendations is an
      emphasis on adherence to hand hygiene guidelines. Other measures that may prevent
      the nosocomial transmission of MRSA include improved antibiotic stewardship,
      staff cohorting, maintenance of appropriate staffing ratios, reductions in length
      of hospital stays, contact isolation, active microbiologic surveillance, and
      better staff education. Currently, the efficacy of many of these individual
      infection control interventions remain in doubt. Many studies reporting
      improvement in infection control outcomes (eg, reduced transmission, decreasing
      prevalence) involve simultaneous institution of several of these measures, making
      it impossible to tease out the effects of any of the individual components.
      Nonetheless, the best approach in the current environment probably involves hand
      hygiene plus a careful assessment of an institution's particular circumstances,
      applying more aggressive procedures such as patient isolation, staff cohorting,
      and active surveillance cultures, as indicated.

PMID- 16813985
TI  - Clinical practice recommendations for peritoneal dialysis adequacy.

PMID- 16813983
TI  - Antimicrobial stewardship.
AB  - Antimicrobial stewardship is a key component of a multifaceted approach to
      preventing emergence of antimicrobial resistance. Good antimicrobial stewardship
      involves selecting an appropriate drug and optimizing its dose and duration to
      cure an infection while minimizing toxicity and conditions for selection of
      resistant bacterial strains. Studies conducted over the years indicate that
      antibiotic use is unnecessary or inappropriate in as many as 50% of cases in the
      United States, and this creates unnecessary pressure for the selection of
      resistant species. Because the pharmaceutical industry pipeline for new
      antibiotics has been curtailed in recent years, and it may be > or = 10 years
      before important new antibiotics to treat certain resistant bacteria find their
      way to market, a premium has been set on maintaining the effectiveness of
      currently available agents. Several strategies, including prescriber education,
      formulary restriction, prior approval, streamlining, antibiotic cycling, and
      computer-assisted programs have been proposed to improve antibiotic use. Although
      rigorous clinical data in support of these strategies are lacking, the most
      effective means of improving antimicrobial stewardship will most likely involve a
      comprehensive program that incorporates multiple strategies and collaboration
      among various specialties within a given healthcare institution. Computer
      assisted software programs may be especially useful in implementing these
      comprehensive programs. The antimicrobial stewardship program at the Hospital of
      the University of Pennsylvania, which has been shown to improve appropriateness
      of antibiotic use and cure rates, decrease failure rates, and reduce healthcare
      related costs, is used as an example in support of this multifaceted,
      multidisciplinary approach. At this time, data from well-controlled studies
      examining the effect of antibacterial stewardship on emergence of resistance are
      limited, but available data suggest that good antibiotic stewardship reduces
      rates of Clostridium difficile-associated diarrhea, resistant gram-negative
      bacilli, and vancomycin-resistant enterococci.

PMID- 16813986
TI  - Research recommendations.

PMID- 16813989
TI  - Clinical practice guidelines for vascular access.

PMID- 16813990
TI  - Clinical practice guidelines for hemodialysis adequacy, update 2006.

PMID- 16813991
TI  - Clinical practice guidelines for vascular access.

PMID- 16813993
TI  - III. Research recommendations.

PMID- 16813992
TI  - Clinical practice recommendation 8: vascular access in pediatric patients.

PMID- 16813997
TI  - Clinical practice guidelines for peritoneal adequacy, update 2006.

PMID- 16813998
TI  - Clinical practice guidelines for peritoneal dialysis adequacy.

PMID- 16813999
TI  - Multiple ligand-binding properties of the lipocalin member chicken alpha1-acid
      glycoprotein studied by circular dichroism and electronic absorption
      spectroscopy: the essential role of the conserved tryptophan residue.
AB  - Multiple ligand-binding properties of the 30-kDa chicken alpha(1)-acid
      glycoprotein (cAGP), a member of the lipocalin protein family, were investigated
      for the first time by using circular dichroism (CD) and UV/Vis absorption
      spectroscopy methods. By measuring induced CD (ICD) spectra, high-affinity
      binding (K(a) approximately 10(5)-10(6) M(-1)) of several drugs, dyes and natural
      compounds to cAGP was demonstrated including antimalarial agents (quinacrine,
      primaquine), phenotiazines (chlorpromazine, methylene blue), propranolol, non
      steroidal antiinflammatory drugs (ketoprofen, diclofenac), tamoxifen, diazepam,
      tacrine, dicoumarol, cationic dyes (auramine O, thioflavine T, ethidium bromide),
      benzo[a]pyrene, L-thyroxine, bile pigments (bilirubin, biliverdin), alkaloids
      (piperine, aristolochic acid), saturated and unsaturated fatty acids. Analysis of
      the extrinsic CD spectra with the study of the covalently modified protein and CD
      displacement experiments revealed that a single Trp26 residue of cAGP conserved
      in the whole lipocalin family is part of the binding site, and it is essentially
      involved in the ligand-binding process via pi-pi stacking interaction resulting
      in the appearance of strong induced CD bands due to the non-degenerate
      intermolecular exciton coupling between the pi-pi* transitions of the stacked
      indole ring-ligand chromophore. The finding that cAGP is able to accommodate a
      broad spectrum of ligands belonging to different chemical classes suggests that
      its core beta-barrel cavity is unusually wide containing overlapping sub-sites.
      Significance of these new data in understanding of the ligand-binding properties
      of other lipocalins, especially that of human AGP, and potential practical
      applications are briefly discussed. Overall, cAGP serves as a simple, ultimate
      model to extend our knowledge on ligand-binding properties of lipocalins and to
      study the role of tryptophan residues in molecular recognition processes.

PMID- 16814000
TI  - Pancreatic tumors: diagnostic patterns by 3D gradient-echo post contrast magnetic
      resonance imaging with pathologic correlation.
AB  - Magnetic resonance (MR) imaging has considerable potential in characterizing
      pancreatic masses. Certain features can be used by the radiologist to establish a
      definitive diagnosis for most pancreatic tumors including ductal adenocarcinoma,
      islet cell tumors, solid and papillary epithelial neoplasms, micro- and
      macrocystic adenoma, and metastases. Recognition of these tumors on imaging is
      important since it often changes the treatment approach and may obviate the need
      for surgery. Recent introduction of 3D gradient recalled echo (GRE) sequence such
      as volumetric interpolated breath hold examination (VIBE) has dramatically
      improved MR imaging by providing dynamic enhanced thin-slice images with fat
      saturation and high signal-to-noise ratio. In this article, special emphasis will
      be placed on the impact of 3D GRE sequence in the diagnosis of pancreatic
      neoplasms with pathologic correlation.

PMID- 16814001
TI  - Hypointensities in the brain on T2*-weighted gradient-echo magnetic resonance
      imaging.
AB  - The objectives of this review are to present various entities that can result in
      hypointensity on brain T2*-weighted gradient-echo (GE) images and to show the
      usefulness of this sequence. There are six etiologies, resulting in hypointensity
      on T2*-weighted GE images, ie, the presence of hemosiderin, deoxyhemogrobin,
      ferritin, calcium, other metals, and air. This sequence is sensitive to magnetic
      susceptibility effect and useful for detecting some kinds of small brain lesions
      and for differential diagnosis in some special conditions.

PMID- 16814002
TI  - Positron emission tomography/computed tomography in the management of Hodgkin's
      disease and non-Hodgkin's lymphoma.
AB  - The incidence of Hodgkin's disease (HD) and Non-Hodgkin's lymphoma (NHL) is
      around 8% of all malignancies. Fortunately, HD and NHL are among the few
      malignancies that are potentially curable with current existing treatment
      modalities, even in advanced or recurrent disease. Accurate staging, early
      therapy monitoring, and posttreatment evaluation of lymphomas are important for
      optimum management of these patients. We reviewed the imaging findings of
      patients with histologically proved lymphoma who underwent staging positron
      emission tomography/computed tomography (PET/CT), early monitoring therapy PET/CT
      (after 3 cycles of chemotherapy), and posttreatment PET/CT. PET/CT imaging
      findings are shown. Utility of PET/CT in recognizing false-positive and false
      negative cases of CT and PET alone is addressed. Pitfalls and diagnostic
      difficulties are analyzed. PET/CT is a new imaging technology that improves the
      evaluation of lymphoma. This review will help the reader to better understand the
      imaging findings and applications of PET/CT in the management of lymphoma.

PMID- 16814003
TI  - Adverse reactions to intravenous iodinated contrast media: an update.
AB  - Assessment of patients before intravenous contrast injection can help in
      detecting predisposing risk factors for adverse reactions to contrast media.
      Early recognition and treatment of acute adverse reactions can prevent morbidity
      and mortality (rare).

PMID- 16814004
TI  - Communicating across the "chasm": Journal of Substance Abuse Treatment and
      Counselor initiate cooperative agreement.

PMID- 16814005
TI  - Multimodal drug addiction treatment: a field comparison of methadone and
      buprenorphine among heroin- and cocaine-dependent patients.
AB  - AIMS: Our objective was to compare the effectiveness of buprenorphine (BUP) and
      methadone maintenance treatment in opiate-addicted patients in a clinical
      nonexperimental setting. DESIGN: We used a naturalistic observational prospective
      study of 24 months' duration. SETTING: Subjects were enrolled and treated at a
      drug addiction outpatient clinic of the National Health System Local Unit in
      Milan, Italy. PARTICIPANTS: Two hundred fifty-seven subjects meeting the DSM-IV
      criteria for opioid dependence and opioid-seeking substitutive pharmacological
      treatment participated in the study. INTERVENTION: One hundred twenty-one
      subjects received BUP at a mean daily dose of 11 +/- 6 mg (median = 8; range = 2
      30) for a mean duration of 249 days. One hundred thirty-six subjects received
      methadone at a mean daily dose of 54 +/- 29 mg (median = 50; range = 4-140) for a
      mean duration of 267 days. MEASUREMENTS: The main efficacy parameters were
      treatment retention rates and illicit substance abuse, as assessed by urinalysis.
      FINDINGS: Retention rates were comparable in both treatment groups, but BUP
      treated subjects had significantly lower rates of illicit opiate consumption (p <
      .0001). CONCLUSIONS: The results confirm that, in a nonexperimental clinical
      practice setting, BUP is as effective as methadone in the treatment of heroin
      dependence, with significantly better opiate abuse control, thus possibly
      allowing longer and more effective treatment programs with reduced relapse rates.

PMID- 16814006
TI  - Staff members are human subjects, too.
AB  - Top management, clinical supervisors, secretaries, government administrators,
      counselors, and patients are all examples of informants and agents used by health
      services researchers as they strive to learn how organizational and managerial
      factors affect the effectiveness, efficiency, quality, and the cost of substance
      abuse treatment and prevention services. Patients are clearly a vulnerable
      population, and researchers in clinical settings, as a rule, strive to protect
      patient safety and rights to privacy. However, as researchers begin to expand the
      scope of their study to the organizational contexts in which services are
      delivered, those responsible for providing services (staff members) are
      frequently enlisted to serve both as informants on policies and practices, and as
      participants acting as agents of the researchers in innovating therapeutic and
      business practices. Researchers need to be mindful that staff members, when
      acting as informants or as agents, are human subjects, too; and, as such,
      research procedures should be designed in a manner that minimizes their risk and
      conforms to sound ethical guidelines. In the interest of stimulating dialogue on
      ways to protect staff members from unintended harm, this essay overviews human
      subjects protection policy, describes examples of risks, and offers suggestions
      for preventing harm when designing studies.

PMID- 16814007
TI  - Predicting DSM-IV dependence diagnoses from Addiction Severity Index composite
      scores.
AB  - This study, using data from the Drug Evaluation Network System and a study
      conducted through the Center for Studies on Addiction of the University of
      Pennsylvania/Philadelphia Veterans Administration Medical Center, sought to
      determine the potential of the Addiction Severity Index (ASI) to serve as a
      screening instrument for Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV) substance dependence. A significant positive correlation
      was found between ASI composite scores (CSs) and DSM-IV diagnoses of dependence
      in both the alcohol (r > .7) and drug (r > .5) domains (p < .01). Receiver
      operating characteristic analyses were run to predict DSM-IV alcohol and drug
      dependence diagnoses from the respective ASI CSs. Results showed good to strong
      prediction; ASI CSs identified dependent clients with approximately 85%
      sensitivity and 80% specificity. We recommend strategies for using ASI CSs as a
      diagnostic screening instrument in both research and treatment delivery
      environments.

PMID- 16814008
TI  - Disseminating evidence-based practices in substance abuse treatment: a review
      with suggestions.
AB  - Although substance abuse professionals are generally open to new and better
      therapeutic methods, most evidence-based treatments do not easily find their way
      into practice. Natural diffusion processes for innovations in substance abuse
      treatments are relatively informal and have yielded a widely acknowledged gap
      between science and community practice. This review focuses on methods for
      effectively disseminating new treatment methods into practice. Therapist manuals
      and one-time workshops are in themselves relatively ineffective in helping
      practitioners gain proficiency in new clinical approaches. Individual performance
      feedback and coaching improve the acquisition of clinical skills. Specific
      incentives for implementation may also be needed to encourage treatment
      providers, programs, and systems to adopt new approaches.

PMID- 16814009
TI  - End-of-treatment outcomes in cognitive-behavioral treatment and 12-step substance
      use treatment programs: do they differ and do they predict 1-year outcomes?
AB  - This study examined changes in treatment-related proximal outcomes from intake to
      follow-up, associations between continuing care and maintenance of proximal
      outcome gains, correlations between specific proximal outcomes and substance use
      outcomes, and potential mediators of treatment effects for 12-step versus
      cognitive-behavioral (CB) substance use disorder (SUD) treatment. The
      participants were 1,873 male veterans seeking SUD treatment at five CB-oriented
      and five 12-step-oriented VA inpatient/residential SUD programs. Patterns of
      change in proximal outcomes were similar across the two program types. After
      discharge, attendance at 12-step groups, but not outpatient treatment, was
      associated with greater maintenance on most proximal outcomes. Only a few
      proximal outcomes at discharge were associated with 1-year substance use; most 1
      year proximal outcomes were associated with 1-year substance use. Having a
      sponsor, reading 12-step materials, attending 12-step meetings, and having an
      abstinence goal appeared to mediate the greater effects of 12-step programs
      (relative to CB programs) on abstinence.

PMID- 16814010
TI  - Improving access to sterile syringes and safe syringe disposal for injection drug
      users in methadone maintenance treatment.
AB  - We evaluated a novel intervention designed to improve access to sterile syringes
      and safe syringe disposal for injection drug users (IDUs) newly enrolled in
      methadone maintenance, through interviews with two sequential cohorts of 100
      recent entrants into a methadone program in the Bronx, NY. A substantial number
      of participants had injected in the previous 6 months, and most continued
      injecting during the early weeks of treatment. The intervention was associated
      with significant behavior changes among IDUs, including increased use of
      pharmacies as a primary source of syringes (11% vs. 37%, p < .05) and decreases
      in both purchasing of syringes on the street (51% vs. 27%, p < .05) and needle
      sharing (40% vs. 7%, p < .01). The intervention had no impact on the prevalence
      of injection or on syringe disposal practices. Our findings suggest that drug
      treatment programs can serve an important role in reducing injection-related risk
      behavior by facilitating access to sterile syringes.

PMID- 16814011
TI  - Characterizing substance abuse programs that treat adolescents.
AB  - Few systematic studies have examined the characteristics of substance abuse
      treatment programs serving adolescents. An expert panel recently identified nine
      key elements of effective adolescent substance abuse treatment. We measured the
      percentage of treatment programs in the United States with at least 10 adolescent
      clients on a given day that reported these elements using data from the 2003
      National Survey of Substance Abuse Treatment Services. This first look into the
      characteristics of facilities serving significant numbers of adolescents
      indicates that many facilities may be lacking in components considered important.
      The most significant measured potential areas for improvement occurred in the
      areas of including mental health as well as medical issues in comprehensive
      assessments and developing curricula to meet the developmental and cultural needs
      of clients. On a more encouraging note, many facilities were conducting discharge
      planning and providing aftercare, although the specifics of these services were
      not determined.

PMID- 16814012
TI  - Measures of fidelity in motivational enhancement: a systematic review.
AB  - The movement to use empirically supported treatments has increased the need for
      researchers and clinical supervisors to evaluate therapists' adherence to and
      competence in particular empirically supported interventions. Motivational
      interviewing (MI) is an empirically supported intervention for substance abuse
      and other behavioral problems. However, for this intervention to work, it must be
      provided with fidelity and skill. This article provides a systematic review of MI
      adherence and competence measures that have been developed and described
      independently elsewhere. Recommendations for refinement of the measures and
      future research are also discussed.

PMID- 16814013
TI  - Is the drug court model exportable? The cost-effectiveness of a driving-under-the
      influence court.
AB  - We assessed the cost-effectiveness of the Rio Hondo driving-under-the-influence
      (DUI) court, a therapeutic court intervention in Los Angeles County targeted to
      repeat DUI offenders. The effectiveness of this court intervention was determined
      through a randomized controlled field experiment. Although prior research does
      not identify differences in alcohol-related or criminal behavior between treated
      and control individuals at follow-up, we found improvements in behavior for all
      program participants regardless of treatment status. A cost-minimization analysis
      found that, on average, costs of the DUI court exceeded traditional court
      expenditures for second-time offenders but produced cost savings for third-time
      offenders. This suggests that implementing a DUI-specific court intervention for
      serious DUI recidivists is a worthwhile investment of public resources. The
      unique legal treatment of DUI offenders in California may hide additional cost
      savings that could be accrued in other jurisdictions through the adoption of DUI
      court programs.

PMID- 16814014
TI  - Recovery-oriented perceptions as predictors of reincarceration.
AB  - The present prospective study explored whether a specific class of client
      subjective assessments predicts later recovery. Measures of client perceptions of
      self-change in substance abusers were obtained a year after release from a prison
      based therapeutic community. Analyses assessed the contribution of these
      perceptions-along with motivation, age, and risk index of social deviancy-in
      predicting reincarceration at 3-year follow-up. Results showed that two factors
      (Individual Growth and Socialization) significantly differentiated
      reincarceration and nonreincarceration at 1-year postrelease and significantly
      predicted reincarceration at 3-year follow-up. Findings underscore the relevance
      of perceptions of self-change early in recovery to later recovery behaviors.
      Research on recovery factors needs a uniform assessment protocol, which organizes
      client perceptions, beliefs, and attributions in accordance with a recovery stage
      framework.

PMID- 16814015
TI  - Outcomes and costs of matching the intensity of dual-diagnosis treatment to
      patients' symptom severity.
AB  - This study evaluated a patient-treatment matching strategy intended to improve
      the effectiveness and cost-effectiveness of acute treatment for dual-diagnosis
      patients. Matching variables were the severity of the patient's disorders and the
      program's service intensity. Patients (N = 230) with dual substance use and
      psychiatric disorders received low or high service-intensity acute care in 1 of
      14 residential programs and were followed up for 1 year (80%) using the Addiction
      Severity Index. Patients' health care utilization was assessed from charts,
      Department of Veterans Affairs (VA) databases, and health care diaries; costs
      were assigned using methods established by the VA Health Economics Resource
      Center. High-severity patients treated in high-intensity programs had better
      alcohol, drug, and psychiatric outcomes at follow-up, as well as higher health
      care utilization and costs during the year between intake and follow-up than did
      those in low-intensity programs. For moderate-severity patients, high service
      intensity improved the effectiveness of treatment in only a single domain (drug
      abuse) and increased costs of the index stay but did not increase health care
      costs accumulated over the study year. Moderate-severity patients generally had
      similar outcomes and health care costs whether they were matched to low-intensity
      treatment or not. For high-severity patients, matching to higher service
      intensity improved the effectiveness of treatment as well as increased health
      care costs. Research is needed to establish standards by which to judge whether
      the added benefits of high-intensity acute care justify the extra costs.

PMID- 16814017
TI  - Economics of stocker production.
AB  - The beef cattle industry, like any industry, is subject to economic signals to
      increase or decrease production according to short-run and long-run market
      conditions. Profitable stocker production is the result of careful matching of
      economic conditions to alternative animal production systems combined with sound
      animal and business management. The economics of stocker production are driven by
      the feeder cattle price-weight relation that combines broad market signals about
      how much production is needed with complex and subtle signals about how that
      production should be accomplished. The result is a dynamic set of values of gain
      that direct producers to adjust the level, type, and timing of stocker production
      according to changing market conditions.

PMID- 16814018
TI  - The stocker cattle supply chain.
AB  - This article discusses supply chain management in the US beef industry and where
      stocker cattle procurement fits in that chain. The supply chain in the US beef
      industry is defined as well as grading mechanisms that signal prices used to
      manage the chain. Sources of stocker cattle are also described.

PMID- 16814019
TI  - Transportation of cattle.
AB  - Until recent years, relatively little attention has been given to beef cattle
      transportation management and research in the United States As oulined in this
      article, it is clear that there are significant physiologic changes occurring in
      cattle as a result of transport and handling. These physiologic changes
      encompass, among others, effects on immune system function, disease incidence,
      and carcass quality. Significant advancements have been made during the past
      decade in the use of appropriate cattle-handling techniques, facility design,and
      research promoting our understanding and the attenuation of transport stress.
      Many issues surrounding livestock transport, such as temperature and ventilation
      during transit, use of rest stops, pretransit feeding regimens, and incidence of
      disease transmission via transport vehicles, need further research to enable
      continued provision of science-based recommendations to the livestock and
      transportation industries.

PMID- 16814020
TI  - Nutrition programs for lightweight calves.
AB  - As long as beef farms have orphaned calves and late-calving cows and as long as
      many small beef herds continue year-round calving,large numbers of lightweight
      calves are likely to be presented to the marketplace. In addition, dairies
      produce male calves that must be grown for beef production as well as heifers
      that need to be developed for milking replacements. All require specialized
      growing programs. With proper planning, nutritional programs for these calves can
      be designed for drylot- and pasture-based systems. Special considerations include
      the reduced feed intake that can occur at the time of weaning, which occurs at
      young ages in these calves, as well as shipping stress and unfamiliarity with
      manufactured feed. Diets must provide more protein and energy than needed for
      older and heavier cattle. Feed form, palatability, and avoidance of digestive
      upset are critical.

PMID- 16814021
TI  - Growing cattle on winter wheat pasture: management and herd health
      considerations.
AB  - Some management and supplementation strategies that have potential to improve
      efficiency of production of wheat pasture stocker and feeder cattle; decrease
      production risk and income variability, and thereby increase growth of the
      industry; and strengthen the economies of rural communities in the southern Great
      Plains are presented in this article.

PMID- 16814022
TI  - Management of forages for stocker cattle.
AB  - Successful grazing management of stockers requires knowledge of plant growth
      characteristics. Maintaining abundant leaf area is critical to support
      photosynthesis and plant growth as well as to provide nutritious grazing for the
      animals. Controlling stocking rate, stock density, and lengths of grazing and
      recovery periods can optimize individual animal rates of gain and gain per acre
      while maintaining pasture productivity. Various plant resources, perennial and
      annual, can be used strategically to provide the quantity and quality of forage
      needed by stockers throughout the year.

PMID- 16814023
TI  - Backgrounding beef cattle.
AB  - Stocker operations differ significantly in management techniques and health
      programs. Critical control points should be identified for each farm and used to
      ascertain the biggest areas for potential improvement so as to allow proper
      allocation of resources. A customized wellness program couples medicine and
      management to minimize the negative impact of disease. A complete program
      involves animal selection, disease prevention, and management. Calves should be
      evaluated and classified into appropriate risk categories regarding treatment,
      management, and performance expectations. Disease prevention strategies should
      involve increasing immune responses while decreasing pathogen exposure and stress
      in cattle. Disease management includes the methods used to minimize the impact of
      illness on the population

PMID- 16814024
TI  - Bovine respiratory disease: pathogenesis, clinical signs, and treatment in
      lightweight calves.
AB  - No matter what disease is being addressed, there are basic steps required for
      successful therapy. Failure to address each step systematically leaves a gap in
      the program that eventually shows up as inconsistency or failure in therapeutic
      efficacy. The focus in this article is on applying these steps in infectious
      bovine respiratory disease challenges in lightweight stocker calves.

PMID- 16814025
TI  - Nonrespiratory diseases of stocker cattle.
AB  - Bovine respiratory disease is the most common health issue affecting stocker
      cattle. There are several nonrespiratory diseases that affect stockers. The more
      common diseases include rumen tympany, infectious bovine keratoconjunctivitis,
      coccidiosis, photosensitization, and foot rot. Accurate diagnosis, early
      treatment, and incorporating appropriate preventive measures can assist cattle
      production.

PMID- 16814026
TI  - Using growth-promoting implants in stocker cattle.
AB  - This article discusses the use of implants in grazing stocker cattle to increase
      the rate of growth and the efficiency of metabolic and economic growth.

PMID- 16814027
TI  - Endoparasite control.
AB  - The gastrointestinal nematodes are considered to be the most important group of
      internal parasites. Gastrointestinal parasitism is a major constraint to animal
      health, productivity, and profitability in grazing livestock production systems.
      The clinical manifestations of infection may range from no apparent effect to
      death. Despite years of research, assessment of production losses in many regions
      of the United States and of the potential impact of gastrointestinal nematode
      control remains to be determined.

PMID- 16814028
TI  - Ectoparasite control.
AB  - The severity of damage that insects, ticks, and mites may have on their bovine
      hosts ranges from undetectable effects on energy expenditure to the death of the
      host. These pest insects can cause direct damage to their hosts by their
      annoyance, irritation, blood feeding, modification of host behavior, and invasion
      of tissues. This direct damage can result in such direct losses as dermatitis,
      anemia,reduction in weight gain performance, devaluation of carcass,injury during
      pest avoidance, injury by chemical control of pests,necrosis, and death. The main
      flies that affect cattle performance and specifically, stockers, are discussed in
      this article.

PMID- 16814029
TI  - Record systems for beef stocker production enterprises.
AB  - The accelerated growth of individual animal identification systems is likely to
      generate significant amounts of data that need to be synchronized, filtered,
      analyzed, managed, and acted on in real time by data-mining software and animal
      health professionals who possess a dual understanding of beef systems production
      and technology associated with management information and record-keeping systems.
      Ultimately, the resulting information can be used seamlessly throughout a
      vertically coordinated production system to conduct management and animal health
      compliance audits, initiate timely animal and product recall measures, and reveal
      complex biologic and economic relations.

PMID- 16814030
TI  - Revisiting the issue of posterior capsule opacification.

PMID- 16814032
TI  - Ease of use versus accuracy.

PMID- 16814033
TI  - Microkeratome-assisted phacoemulsification.

PMID- 16814034
TI  - Ease of use versus accuracy.

PMID- 16814035
TI  - Measurement of the spatial shift of the pupil center.

PMID- 16814037
TI  - A question of semantics.

PMID- 16814038
TI  - Consultation section. Cataract surgical problem.

PMID- 16814047
TI  - Bimanual microphaco for posterior polar cataracts.
AB  - We describe a technique in which bimanual microphacoemulsification technique
      through 2, 1.4 mm incisions is performed for posterior polar cataract extraction.
      The low-infusion and low-vacuum system provides good anterior chamber stability
      and followability. The irrigation and aspiration handpieces are interchangeable,
      enabling removal of the lens fragments without hydrodissection or nucleus
      rotation. Only 1 (12.5%) of the 8 cases presented here was complicated by
      posterior capsule rupture. This occurred after epinucleus removal without any
      vitreous disturbance. The bimanual microphacoemulsification technique appears to
      minimize the risk for complications, allowing posterior polar cataract extraction
      to be performed more safely.

PMID- 16814048
TI  - Rescue of failed filtering blebs with ab interno trephination.
AB  - We evaluated the effectiveness of ab interno automated trephination as a
      technique for rescuing failed mature filtering blebs. A retrospective chart
      review of 40 failed blebs of 38 patients who had a posttrephination follow-up
      period of at least 3 months was done. With success defined as intraocular
      pressure (IOP) <21 mm Hg and at least a 20% reduction from baseline on the same
      or fewer number of pretrephination medications, 30/40 eyes (75%) fit these
      criteria over the entire course of follow-up. Among all 40 eyes, there was a
      significant reduction of IOP from pretrephination to 3 months (P<.001). The
      percentage of patients requiring 2 or more medications declined from 90%
      pretrephination to 21% at 3 months (P<.0001), and was stable thereafter. Some
      patients were able to eliminate all medications. Patients who did not meet the
      criteria of success regained successful IOP control with other modalities of
      management. Complications were few. We believe that ab interno trephination is an
      excellent option for rescuing selected failed filtering blebs.

PMID- 16814049
TI  - Correction of post-keratoplasty astigmatism with keratotomies in the host cornea.
AB  - We evaluated the effects of astigmatic keratotomy performed in the host cornea to
      treat astigmatism after penetrating keratoplasty. In 11 patients with high post
      keratoplasty astigmatisms (mean 9.02 diopters [D]; range 5.5 to 17.4 D), an
      arcuate keratotomy was performed in the host cornea. The mean incision depth was
      575 mum (range 500 to 600 mum). The refractive data were analyzed using the
      Alpins method for vector analysis. The mean keratometric cylinder decreased to
      3.41 D (range 0.9 to 5.3 D). The mean surgically induced astigmatism achieved was
      7.3 +/- 3.89, with a mean correction index of 0.82 +/- 0.34. No microperforations
      were observed, and neither graft decompensation nor rejection occurred.
      Astigmatic keratotomy performed in the host cornea was a safe procedure to reduce
      post-keratoplasty astigmatism. The procedure offers the potential for correction
      of the astigmatism and has satisfactory predictability.

PMID- 16814050
TI  - Routine posterior optic buttonholing for eradication of posterior capsule
      opacification in adults: report of 500 consecutive cases.
AB  - PURPOSE: To study the efficacy of posterior optic buttonholing (POBH) through a
      primary posterior capsulorhexis (PPCCC) to preserve full capsular transparency,
      and its potential as a routine alternative to standard in-the-bag implantation of
      sharp-edged optic intraocular lenses (IOLs). SETTING: Department of
      Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: After
      standard cataract removal, a PPCCC 4.0 to 5.0 mm in diameter was performed and
      the optic of a 3-piece IOL buttonholed posteriorly. One third of the eyes
      additionally had extensive anterior capsule polishing. All surgeries were
      performed under topical anesthesia. RESULTS: The first 500 consecutive surgeries
      were evaluated. In 11 eyes, POBH was not performed as planned. In 4 cases,
      anterior capsulorhexis fixation of the optic was used as an alternative. In the
      early series, vitreous entanglement was seen in 5 eyes, of which 1 case prompted
      translimbal anterior vitrectomy. No case of cystoid macula edema was observed.
      One case of peripheral retinal detachment in a highly-myopic eye 4 months
      postoperatively appeared to be unrelated to the surgery. All lenses were well
      centered without tilt, and both capsule leaves remained clear especially after
      additional polishing. CONCLUSION: Posterior optic buttonholing precludes lens
      epithelial cells from accessing the retrolental space. The sandwiched posterior
      capsule blocks optic contact and thus fibrosis of the anterior capsule. Posterior
      optic buttonholing avoids after-cataract independent of optic edge design.
      Anterior capsule polishing adds to its efficacy by excluding any residual
      fibrosis. Surgery under topical anesthesia was well-controlled and safe.
      Posterior optic buttonholing may become a routine alternative to standard in-the
      bag IOL implantation when supported by a longer follow-up.

PMID- 16814051
TI  - Opacification of the Hydroview H60M intraocular lens: total patient recall.
AB  - PURPOSE: To report the prevalence of intraocular lens (IOL) opacification and
      related clinical features in patients implanted with Hydroview IOL. SETTING:
      Gloucestershire Eye Unit, Gloucestershire, United Kingdom. METHODS: A total of
      1330 eyes of 1265 patients who had cataract surgery with Hydroview IOL
      implantation between September 2000 and April 2001 were reviewed between April
      and October 2004. The visual acuity, visual symptoms, IOL status, and associated
      ocular comorbidity were recorded. RESULTS: One hundred ninety-three (14.5%) of
      1330 eyes had evidence of IOL opacification. A total of 56 (4.2%) had visually
      significant opacification and had IOL exchange. The prevalence of IOL
      opacification ranged from 1.1% in patients who had surgery in September 2000 to
      36.3% in the December 2000 group. In eyes with IOL opacification, the visual
      symptoms were decreased vision (57%), glare (32%), and mistiness of vision (27%).
      One hundred forty-four eyes (75%) with IOL opacification had visual acuity of
      6/12 or better; 21.5% of diabetic eyes had IOL opacification compared with 14.3%
      of nondiabetic eyes (P =.06); 20.5% of glaucomatous eyes had IOL opacification
      compared with 14.0% of nonglaucomatous eyes (P = .033). CONCLUSIONS: This is the
      first large sample recall of patients implanted with the Hydroview H60M IOL. The
      overall prevalence of IOL opacification was 14.5%, with peak prevalence in
      patients who had surgery in December 2000.

PMID- 16814052
TI  - Topography-guided customized laser-assisted subepithelial keratectomy for the
      treatment of postkeratoplasty astigmatism.
AB  - PURPOSE: To assess topography-assisted corneal wavefront excimer laser surface
      ablation for the correction of ametropia and irregular astigmatism after
      keratoplasty. SETTING: Department of Ophthalmology, St. Thomas' Hospital, London,
      United Kingdom. METHODS: In this pilot study, 15 patients (16 eyes) who were
      intolerant of spectacle and contact lens correction due to astigmatic
      anisometropia after keratoplasty (15 penetrating and 1 lamellar) had topography
      assisted customized excimer laser treatments. Corneal topographic data using a
      Keratron Scout, Placido disk system allowed for preoperative analysis of
      wavefront anomalies of the anterior corneal surface from which a customized
      excimer laser correction of both lower-order aberrations (LOAs) and higher-order
      aberrations (HOAs) was prepared (ORK software) for treatment with a Schwind
      Esiris flying-spot laser. All eyes had laser-assisted subepithelial keratectomy
      (LASEK) using 15% alcohol with a 20-second to 30-second application. Four eyes
      received an application of mitomycin-C (MMC) 0.2 mg/mL for 1 minute after stromal
      ablation. RESULTS: The mean preoperative spherical equivalent (SE) was -3.50
      diopters (D) +/- 3.97 (SD) (range +1.625 to -9.25 D). The preoperative
      cylindrical error was -7.2 D (range -2.75 to -13.5 D). The programmed laser
      correction was -3.14 D (range +1.62 to -9 D) with a maximum attempted cylindrical
      correction of -7 D. Adherent LASEK epithelial flaps along suture lines and the
      graft-host junction were noted in 9 eyes (56%), although it was possible to
      obtain and replace a partial flap. A follow-up of 18 months was achieved in all
      eyes. At the final follow-up visit, the mean postoperative SE was -1.08 +/- 1.85
      D (range +3 to -4.78 D) (P<.01, F<.01). Ten eyes (62.5%) were within +/-1 D of
      the intended correction. The mean postoperative cylindrical error was -2.72 D
      (range -0.5 to -6.5 D) (P<.001), with vector analysis demonstrating a mean 6.23 D
      correction. Analysis of HOAs using a 6.0 mm pupil size demonstrated a significant
      reduction of higher-order root mean square (RMS) (P<.002), trefoil (P<.005), and
      4th-order spherical aberration (P<.02) at 18 months compared with preoperative
      values. Uncorrected visual acuity improved in all eyes (P<.0001). Best spectacle
      corrected visual acuity was unchanged or improved in 13 eyes (81%) and worse in 2
      eyes by 1 line; 1 eye lost 3 lines due to an increase in preexisting cataract. In
      eyes that did not receive MMC, corneal haze (grade II to IV) was encountered in 3
      eyes (27%). One eye required phototherapeutic keratectomy with MMC application at
      12 months. Of the 4 eyes treated with MMC, 1 had trace haze and 3 had no
      detectable haze. There were no reported cases of epithelial instability, ectasia,
      or graft rejection. CONCLUSIONS: Topography-assisted customized LASEK was
      effective in the correction of postkeratoplasty astigmatism. A significant
      improvement of both LOAs and HOAs was obtained with good refractive stability for
      over 18 months. Iatrogenic haze typically occurred but appeared to be minimized
      with adjunctive use of intraoperative MMC.

PMID- 16814053
TI  - Visual and refractive results of combined PTK/PRK in patients with corneal
      surface disease and refractive errors.
AB  - PURPOSE: To investigate the changes in symptoms, refraction, and visual acuity
      (VA) in patients with corneal surface disease and refractive errors who had
      phototherapeutic keratectomy (PTK) combined with photorefractive keratectomy
      (PRK). SETTING: University-based referral practice. METHODS: Patients with myopia
      or astigmatism and map-dot-fingerprint dystrophy or recurrent erosions were
      treated. The corneal epithelium was removed with a 64 blade, and laser was
      performed using a Visx Star S3 laser. RESULTS: Nineteen eyes of 14 patients were
      treated. Preoperatively, mean myopia was -3.76 diopters (D) (range -7.50 to -0.75
      D), mean astigmatism was +0.96 D (range 0.00 to +2.25 D), and mean UCVA was
      20/400. At 3 months, mean myopia was -0.53 D (range -1.75 to +0.75 D) (P<.001),
      mean astigmatism was +0.58 D (range 0.00 to +1.25 D) (P = .05), and mean
      uncorrected VA was 20/23 (P<.001). At 6 months, mean myopia was -0.31 D (range 
      1.00 to +0.75 D) (P<.001), mean astigmatism was +0.56 D (range 0.00 to +1.25 D)
      (P = .05), and mean uncorrected VA was 20/23 (P<.001). The change in astigmatism
      was confirmed by vector analysis. Only 1 patient lost 1 line of acuity, and all
      patients were asymptomatic. CONCLUSION: Patients with myopia and astigmatism and
      symptomatic epithelial basement membrane disorders who had PTK/PRK had resolution
      of their symptoms and nearly achieved emmetropia. Therefore, this procedure is
      safe and effective for patients with corneal surface disease and myopia.

PMID- 16814054
TI  - One thousand consecutive IntraLase laser in situ keratomileusis flaps.
AB  - PURPOSE: To measure laser in situ keratomileusis (LASIK) flap dimensions created
      with the IntraLase FS (IL) laser (Intralase Corporation). SETTING: Private
      practice, San Diego, California, USA. METHODS: Consecutive LASIK flaps created
      with the IL were measured with subtraction ultrasound at primary and enhancement
      surgeries. Data were stored in Outcomes Analysis Software and analyzed using MS
      Excel (Microsoft Corporation) and SSPS software. RESULTS: The mean achieved flap
      thickness exceeded the attempted by 9.4 to 34.3 mum. The standard deviation
      varied from +/-10.2 to +/-21.7 mum. Preoperative corneal thickness and power did
      not affect achieved flap thickness. Seventy-three percent of mate eye flaps were
      within +/-15 mum of each other for the 90 mum attempted. The same flaps measured
      at enhancement were thicker than the primarily measured flaps (n = 58). Diffuse
      lamellar keratitis and slipped flaps were eliminated with experience. There were
      no decentered or irregular flaps, epithelial defects, or flap perforations.
      CONCLUSIONS: Compared with published results of mechanical microkeratomes, the IL
      reduced the standard deviation of flap thickness as well as the achieved range.
      It eliminated physical complications associated with mechanical flap creation,
      and the impact of preoperative pachymetry and corneal power, thereby permitting
      more myopia to be corrected without risking deep ablations.

PMID- 16814055
TI  - Corneal thickness measurements in normal and keratoconic eyes: Pentacam
      comprehensive eye scanner versus noncontact specular microscopy and ultrasound
      pachymetry.
AB  - PURPOSE: To compare central corneal thickness (CCT) measurements taken with the
      Pentacam comprehensive eye scanner (CES), noncontact specular microscopy (SM),
      and ultrasound pachymetry (UP) in normal and keratoconic corneas. SETTING:
      Department of Ophthalmology, Ankara University School of Medicine, Ankara,
      Turkey. METHODS: In a prospective study, 3 CCT measurements were taken with the
      Pentacam CES, SM, and UP in that sequence from 1 eye of 45 consecutive patients
      with myopia (group A) and 62 consecutive patients with keratoconus (group B).
      Eyes with keratoconus were further divided into 3 subgroups, mild, moderate, and
      severe, according to the mean keratometry readings. RESULTS: Pentacam CES (r =
      0.994) and UP (r = 0.993) demonstrated very high and comparable reproducibility
      in group A. In group B, Pentacam CES displayed better reproducibility (r = 0.988)
      than UP (r = 0.969) and SM (r = 0.901). The mean CCT measurements of Pentacam CES
      and UP were not significantly different in group A (P = .37) and in eyes with
      mild keratoconus (P = .29), whereas significant differences between all
      instrument pairs were evident in group B and in moderate and severely keratoconic
      eyes (P<.05). Noncontact SM measurements were significantly smaller than those of
      Pentacam CES and UP in all groups (P<.05) when a measurement could be obtained.
      There were significant linear correlations between CCT measurements of Pentacam
      CES, UP, and noncontact SM in groups A, B, and mildly keratoconic eyes (P<.001).
      CONCLUSIONS: Results suggest that whereas Pentacam CES and UP may be used
      interchangeably in normal eyes in the clinical setting for the measurement of
      CCT, one should be cautious interpreting corneal thickness data from Pentacam
      CES, UP, and particularly SM in eyes with keratoconus. Whereas, in normal and
      mildly keratoconic eyes, Pentacam CES and UP demonstrated very high and
      comparable reproducibility, in moderately keratoconic eyes, Pentacam CES readings
      showed better reproducibility than UP.

PMID- 16814056
TI  - Intracorneal ring segments for keratoconus correction: long-term follow-up.
AB  - PURPOSE: To evaluate long-term results and stability of intracorneal ring segment
      (Intacs) implantation for keratoconus correction. SETTING: Vissum, Instituto
      Oftalmologico de Alicante and University of Miguel Hernandez, Alicante, Spain.
      METHODS: This retrospective study comprised 13 eyes operated on between April
      2000 and December 2001 that had Intacs implantation for keratoconus correction.
      The outcomes were evaluated at 6, 12, 24, and 36 months in all eyes and at 48
      months (6 eyes). RESULTS: Mean best spectacle-corrected visual acuity (BSCVA)
      increased from 0.46 (20/50) preoperatively to 0.66 (20/30) postoperatively (P< or
      =.001). Mean decrease of inferior-superior (I-S) asymmetry was 2.81 diopters (D)
      (P< or =.02), and the average K-value was 3.13 D (P< or =.001). Mean difference
      between 6 and 36 months (stability) showed no significant difference regarding
      BSCVA (P< or =.5) and I-S asymmetry (P< or =.6). Although a significant increase
      was noticed in the average K by 1.67 D (P< or =.002), at 36 months it did not
      reach the initial preoperative values. CONCLUSION: Intacs increased the BSCVA and
      decreased I-S asymmetry with stability up to 36 months. In spite of the decrease
      of the K-values at 6 months, a further significant increase was detected 36
      months after surgery.

PMID- 16814057
TI  - Intacs adjustment surgery for keratoconus.
AB  - PURPOSE: To describe the visual outcome of keratoconic eyes managed with Intacs
      (Addition Technology, Inc.) that required additional Intacs surgery (defined as
      any combination of removal, exchange, addition, or shifting of an Intacs
      segment). SETTING: Private refractive surgery center, Jerusalem, Israel. METHODS:
      This retrospective noncomparative interventional consecutive small case series
      studied all eyes of a cohort of 58 keratoconic eyes managed with Intacs that had
      additional Intacs surgery. The uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity, manifest refraction, videokeratography, and patient
      questionnaires on visual function were assessed. These outcome measures were
      compared before Intacs implantation, before Intacs adjustment, and 1 year after
      the final Intacs adjustment. Eyes having any intervention other than Intacs
      surgery were excluded. RESULTS: Of 58 keratoconic eyes managed with Intacs, 7 had
      additional Intacs surgery. After the initial Intacs surgery, 6 of these eyes had
      UCVA < or =20/100 and 1 had UCVA of 20/50. After the final Intacs adjustment, 3
      eyes achieved UCVA > or =20/40, 5 achieved UCVA > or =20/70, and 2 remained
      <20/200. The indications for Intacs adjustments were increased astigmatism in 4
      eyes, induced hyperopia (overcorrection) in 3, and undercorrection in 1. One eye
      had both surgically induced astigmatism and hyperopia. Induced astigmatism and
      hyperopia were most often managed by removing the superior segment. The
      undercorrected eye, having initially received a single inferior segment, was
      treated by implanting a superior segment. CONCLUSIONS: Approximately 10% of
      keratoconic eyes managed with Intacs may require Intacs adjustment surgery, which
      often has a good outcome.

PMID- 16814058
TI  - Intrastromal corneal ring in penetrating keratoplasty: evidence-based update 4
      years after implantation.
AB  - PURPOSE: To report the clinical outcomes of an intrastromal corneal ring (ISCR)
      used in penetrating keratoplasty (PKP) that was designed to decrease
      postoperative corneal astigmatism, stabilize refraction, accelerate healing, and
      possibly reduce immune reactions. MATERIALS AND METHODS: An 8 mm cobalt-titanium
      molybdenum alloy ring was sutured into the PKP wounds. A prospective study
      compared the outcomes of PKP in 179 consecutive cases with a ring (Group 1) and
      101 consecutive patients without a ring (Group 2). The ring was used in different
      types of endoepithelial degeneration as well as in keratoconus stage IV. Patients
      with macular pathology were included. RESULTS: The mean age of Group 1 patients
      was 67 years (range 9 to 96 years). Postoperative best corrected visual acuity
      after 1 year was almost identical in both groups (20/42 in Group 1 and 20/45 in
      Group 2) as were the cylinder values (Group 1, 2.64 diopters [D] +/- 1.44 (SD)
      versus Group 2, 2.83 +/- 1.52 D). There were 2 immune reactions in group I as
      compared to 6 (1.2% vs 7%, P value 0.02) in group II within 4 years of the
      procedure. Evaluation was performed by the Kaplan-Meier method. CONCLUSION:
      Advantages of the ISCR were observed outside the targeted goals of improving the
      amount of astigmatism and maintaining refractive stability. Best corrected visual
      acuity and cylinder development were similar in Groups 1 and 2, whereas, there
      was a highly reduced immune rejection rate. The ring also appeared to act as a
      barrier to superficial vessels.

PMID- 16814059
TI  - Age-related behavior of posterior chamber lenses in myopic phakic eyes during
      accommodation measured by anterior segment partial coherence interferometry.
AB  - PURPOSE: To evaluate age-related position shifts of the crystalline lens and the
      implantable contact lens (ICL, Staar Surgical) by a new, commercially available,
      anterior segment partial coherence interferometer, the ACMaster (Carl Zeiss
      Meditec), during accommodation in myopic eyes. SETTING: ALZ Augenklinik, Munich,
      Germany. METHODS: Fifty-three eyes of 29 consecutive patients were measured after
      myopic ICL implantation before and during subjective accommodation to a stimulus
      of 3 diopters (D) by anterior segment partial coherence interferometry (PCI).
      Nine eyes were also measured with a 5.00 diopters (D) stimulus; 14 eyes were
      measured repeatedly at different visits. The mean patient age was 33 years +/- 9
      (SD) (range 21 to 59 years). The preoperative mean sphere was -7.6 +/- 1.9 D
      (range -5.0 to -11.5 D) and the cylinder, -1.4 +/- 1.1 D (range 0 to -4.25 D).
      RESULTS: Older patients had a tendency toward smaller vaults on desaccommodation
      between the ICL and the crystalline lens compared to younger individuals. In
      younger patients, there was a decrease of the vault on accommodation, whereas it
      increased in older persons (P = .005). During accommodation, the more the
      anterior lens surface shifted forward, the more the ICL bulged (P = .005). The
      change in vaulting was significantly larger at 5.00 D than at 3.00 D
      accommodation stimulus (P = .012). CONCLUSIONS: The behavior of ICLs in relation
      to the crystalline lens during accommodation varied with age and could be shown
      by PCI. The position shift of the ICL depended on the initial vault at
      desaccommodation and the ability of the anterior lens surface to bulge forward.
      Even though the crystalline lens stiffened, and therefore accommodation
      deteriorated with age, there was still a movement of the ICL, pointing to the
      role of the ciliary muscle movement in accommodation.

PMID- 16814060
TI  - Iridocyclitis associated with angle-supported phakic intraocular lenses.
AB  - PURPOSE: To evaluate incidence, features, risk factors, and prognosis of
      iridocyclitis after angle-supported phakic intraocular lens (IOL) implantation.
      SETTING: Private practice, Siena, Italy. METHODS: This retrospective analysis
      comprised 356 consecutive eyes of 212 patients. In myopic eyes, the ZSAL-4 IOL
      (205 eyes of 125 patients) or the ZSAL-4 Plus IOL (106 eyes of 63 patients) was
      used. In hyperopic eyes (45 eyes of 24 patients), the Type 54 IOL was implanted.
      Haptic posterior angulation was 19 degrees (ZSAL-4), 23 degrees (ZSAL-4 Plus),
      and 14 degrees (Type 54). RESULTS: Clinically significant iridocyclitis occurred
      in 11 eyes (3.1%) of 11 patients. Mean patient age was 37.3 years +/- 9.4 (SD).
      Sixty-four percent were male (odds ratio [OR], 3.0; 95% confidence interval [CI],
      0.8 to 7.4, not statistically significant). Iridocyclitis was observed in 4.4% of
      hyperopic eyes (OR, 1.6; 95% CI, 0.3 to 7.4; not statistically significant) and
      in 2.9% of myopic eyes. In myopic eyes, it followed the implantation of ZSAL-4
      IOL in 3.9% of eyes (OR, 4.1; 95% CI, 0.5 to 33.6; not statistically
      significant), and of ZSAL-4 Plus IOL in 1%. Mean time from surgery was 8.5 +/-
      10.6 months). Presentation included aqueous flare (100%), posterior synechiae
      (82%), blurred vision (82%), redness (36%), pain (27%), IOL precipitates (18%),
      and angular synechiae (9%). Only 1 patient had recurrences, leading to IOL
      explantation and cataract surgery. After topical therapy, best spectacle
      corrected visual acuity was fully recovered in 9 of 11 eyes. CONCLUSION:
      Iridocyclitis can occur months or years after the implantation of angle-supported
      phakic IOLs. No statistically significant risk factors were identified.
      Functional prognosis is generally good.

PMID- 16814061
TI  - Effect of temporal clear corneal phacoemulsification on intraocular pressure in
      eyes with prior Ahmed glaucoma valve insertion.
AB  - PURPOSE: To evaluate the effect of temporal clear corneal phacoemulsification on
      intraocular pressure (IOP) in eyes after Ahmed glaucoma valve insertion. SETTING:
      Department of Ophthalmology, Sungkyunkwan University School of Medicine, Samsung
      Medical Center, Seoul, Korea. METHODS: The files of 13 patients who received
      phacoemulsification after Ahmed glaucoma valve insertion were reviewed in this
      retrospective case series. Visual acuity, IOP, and the number of glaucoma
      medications before phacoemulsification were used as a baseline for comparison
      with the values at various follow-up intervals. RESULTS: The mean IOP before
      phacoemulsification was 15.1 mm Hg +/- 3.6 (SD). Postoperatively, it was 12.8 +/-
      4.5 mm Hg, 13.1 +/- 3.6 mm Hg, 16.4 +/- 5.2 mm Hg, 15.8 +/- 4.0 mm Hg, 16.1 +/-
      3.9 mm Hg, 15.3 +/- 4.1 mm Hg, and 15.2 +/- 3.4 mm Hg at 1 day after 1 week, at
      1, 2, 6, and 12 months, and at last visits, respectively. The mean IOP did not
      differ significantly from the prephacoemulsification value at any follow-up. The
      number of glaucoma medications increased significantly after phacoemulsification
      (P = .031), and 6 of 13 eyes required additional glaucoma medication because of
      IOP elevation at approximately 1 month. CONCLUSIONS: Temporal clear corneal
      phacoemulsification did not increase IOP significantly in eyes with prior Ahmed
      glaucoma valve insertion. However, some eyes experienced an IOP elevation 1 month
      after phacoemulsification and required glaucoma medication.

PMID- 16814062
TI  - Assessment of pupil size under different light intensities using the Procyon
      pupillometer.
AB  - PURPOSE: To study the relationship between pupil size and light intensity using
      the Procyon pupillometer. SETTING: University based clinic. METHODS: In this
      retrospective study, 20 consecutive patients had pupil size assessment with the
      Procyon pupillometer under 3 different light conditions--4, 0.4, and 0.04 lux.
      Correlation was established using the log unit of the light intensity and pupil
      size. RESULTS: The correlation coefficient for the association between pupil size
      and log unit of light intensity in all eyes was significant (P<.001). The mean
      correlation coefficient for the association between pupil size and log unit of
      light intensity in all patients was 0.968 +/- 0.089 (SD) in the right eye and
      0.970 +/- 0.031 in the left eye. CONCLUSION: The linear relationship between the
      pupil size and the log unit of the light intensity showed a tight correlation in
      all cases. These results can be useful in the comparing pupil size with
      pupillometers that work under different light conditions.

PMID- 16814063
TI  - Incidence and outcomes evaluation of endophthalmitis management after
      phacoemulsification and 3-piece silicone intraocular lens implantation over 6
      years in a single eye unit.
AB  - PURPOSE: To evaluate the incidence and outcomes of management of endophthalmitis
      following phacoemulsification and 3-piece silicone intraocular lens (IOL)
      implantation in a single eye unit over a 6-year period. SETTING: Shrewsbury and
      Telford Hospital, NHS Trust, Shrewsbury, United Kingdom. METHODS: Forty-four
      cases of endophthalmitis following phacoemulsification and 3-piece silicone IOL
      implantation were identified between January 1, 1998, and December 31, 2003. All
      the data related to the endophthalmitis cases were prospectively collected. The
      total number of cataract surgeries was identified from the hospital information
      technology department through coding data. RESULTS: There were 44 cases of
      endophthalmitis following 12 362 phacoemulsification cataract extractions
      (incidence 0.36%). The incidence of endophthalmitis with a silicone polypropylene
      IOL (0.67%) was significantly higher (P<.0005) than with a silicone poly(methyl
      methacrylate) (PMMA) IOL (0.24%). Thirty-six patients (81.8%) had vitreous tap
      while 8 patients (18.2%) had vitrectomy. Twenty cases (45.5%) were culture
      positive. Visual acuity was 6/12 or better in 30 patients (68.8%). There was weak
      correlation between visual acuity at presentation and final visual outcome
      (Pearson correlation r = 0.33, P = .029). Final visual acuity was not
      significantly related to culture results (P = .85, Mann-Whitney U test) or type
      of presentation (P = .52, Mann-Whitney U test). CONCLUSIONS: In this first single
      center study to report incidence of endophthalmitis following phacoemulsification
      and silicone IOL implantations alone, the incidence of endophthalmitis was
      significantly higher with silicone polypropylene IOLs than with silicone PMMA
      IOLs and the overall incidence of endophthalmitis following phacoemulsification
      surgery was higher than most of the published data.

PMID- 16814064
TI  - Sub-Tenon's anesthesia with aspirin, warfarin, and clopidogrel.
AB  - PURPOSE: To review the frequency of hemorrhagic complications with sub-Tenon's
      anesthesia in patients on aspirin, warfarin or clopidogrel. SETTING: St. James's
      University Hospital, Leeds, United Kingdom. METHODS: Data were collected
      prospectively for patients having elective phacoemulsification under sub-Tenon's
      anesthesia. Seventy-five patients were on aspirin, 65 were on warfarin, and 40
      were on clopidogrel. Seventy-five patients on no anticoagulants were used as the
      control group. No changes in the anticoagulant regimen were made prior to
      surgery. RESULTS: No sight-threatening hemorrhagic complications were noted, and
      no surgery was postponed or cancelled due to an anesthesic complication.
      Subconjunctival hemorrhage occurred in 19% in the control group, 40% in the
      clopidogrel group, 35% in the warfarin group, and 21% in the aspirin group. The
      warfarin and clopidogrel groups had the highest incidence of subconjunctival
      hemorrhage (P<.05). The incidence of hemorrhages involving more than 1 quadrant
      was highest in these 3 groups; however, this did not achieve statistical
      significance (P = .37, Fisher exact test). CONCLUSION: Data from this study
      support the continued use of anticoagulant agents among routine users during
      cataract surgery using a sub-Tenon's block.

PMID- 16814065
TI  - In vitro behavior of ophthalmic viscosurgical devices during phacoemulsification.
AB  - PURPOSE: To evaluate the behavior and aspiration of several ophthalmic
      viscosurgical devices (OVDs) during phacoemulsification. SETTING: Department of
      Ophthalmology, Tokyo Dental College Suidobashi Hospital, Tokyo, Japan. METHODS:
      Cohesive OVDs (sodium hyaluronate 1.0% [Healon and Provisc]), dispersive OVDs
      (sodium hyaluronate 3.0%-chondroitin sulfate 4.0% [Viscoat]), and new-generation
      OVDs such as viscoadaptive (sodium hyaluronate 2.3% [Healon5]) and
      viscodispersive (hyaluronic acid 1.65%-chondroitin sulfate 4.0% [DisCoVisc])
      OVDs, were stained with fluorescein sodium. The movement of the OVDs during
      simulated cataract surgery was recorded in porcine eyes under an operating
      microscope and with a side-view video camera. The initial and complete aspiration
      times of each OVD during phacoemulsification using 20 and 40 mL/min flow rates
      and sleeves and the removal times using the irrigation and aspiration (I/A) tip
      at the end of surgery were evaluated from the recorded videos. RESULTS: The
      complete aspiration time of the cohesive OVDs was less than 3 seconds but up to
      20 seconds with a low flow rate of 20 mL/min with a smaller sleeve. Other OVDs
      remained in the anterior chamber during phacoemulsification with both flow rates.
      The removal time for cohesive OVDs was less than 4 seconds and for new-generation
      OVDs, 10 to 15 seconds. The dispersive OVD required a significantly (P<.05)
      longer removal time than other OVDs. CONCLUSIONS: Cohesive OVDs are removed
      easily during phacoemulsification; however, the aspiration rate can be affected
      by fluidics. New-generation OVDs, such as Healon5 and DisCoVisc, remained in the
      anterior chamber during phacoemulsification and were removed easily by I/A at the
      end of surgery. The behavior of these OVDs is preferable during
      phacoemulsification.

PMID- 16814066
TI  - Thermal inertia associated with ultrapulse technology in phacoemulsification.
AB  - PURPOSE: To determine whether very short pulses of ultrasound (5 to 6
      milliseconds) have less heat propagation in biological tissue (thermal inertia)
      than traditional pulses (50 milliseconds). SETTING: Department of Ophthalmology
      and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City,
      Utah. METHODS: Thermal testing was done in balanced salt solution (BSS) and in
      eye-bank eyes. In the same fresh human eye-bank eye, net temperature increase
      after 20 seconds of ultrasound (50 milliseconds on and 50 milliseconds off) was
      compared with the increase after 6 milliseconds on and 12 milliseconds off with
      the same phacoemulsification unit. The same experiment and setting was run in BSS
      and the eye-bank ratios compared with the BSS ratios. Twenty runs were done at
      each power setting in BSS and 22 in the eye-bank eye. RESULTS: There was 10.9%
      less heat generated with 6-millisecond pulses of ultrasound in limbal tissue than
      in BSS compared with 50-millisecond pulses of ultrasound (P = .0002). CONCLUSION:
      Very short pulses of ultrasound (5 to 6 milliseconds) propagated less thermal
      energy in limbal tissue than in BSS compared with 50-millisecond ultrasound
      pulses.

PMID- 16814067
TI  - Active oxygen processing for acrylic intraocular lenses to prevent posterior
      capsule opacification.
AB  - PURPOSE: To evaluate active oxygen processing on the surface of acrylic
      intraocular lenses (IOLs) to prevent secondary posterior capsule opacification
      (PCO). SETTING: Department of Ophthalmology, Dokkyo Medical University School of
      Medicine, Mibu City, Tochigi, Japan. METHODS: Acrylic IOLs were prepared, and
      ultraviolet (UV)/ozone (UV/O3) or argon plasma was irradiated to the surface of
      the IOLs. Elemental analysis (electron spectroscopy for chemical analysis [ESCA])
      of the IOL surfaces was performed to confirm surface modification. Changes
      produced by UV/O3 or argon plasma treatment were examined for fibronectin and
      lens epithelial cell (LEC) adhesion. To evaluate the PCO prevention by treated
      IOLs, 8-week-old albino rabbits were used. The rabbit eyes randomly had
      phacoemulcification and implantation of 3 different IOLs: the UV/O3-treated IOLs,
      argon plasma-treated IOLs, and the control IOLs. After 2 weeks, the rabbits were
      killed and their globes were dissected and fixed using formaldehyde 10%. The PCO
      was observed using light microscopy (DX51, ORIMPUS) after hematoxylin and eosin
      staining. RESULTS: Comparison of IOL surface composition by ESCA showed an
      increase in nitrogen content and hydroxyl substitute and carboxyl substitute
      groups on surfaces of treated IOLs. The fibronectin adhesion and the LEC adhesion
      on the UV/O3-treated and argon plasma-treated samples were increased. In the
      untreated group, there was statistically significant inhibition of PCO formation
      in the UV/O3-treated and argon plasma-treated groups. CONCLUSION: Active oxygen
      processing and argon plasma irradiation on the surface of IOLs was effective in
      preventing secondary PCO after cataract surgery.

PMID- 16814068
TI  - Ingestion of IH636 grape seed proanthocyanidin extract to prevent selenite
      induced oxidative stress in experimental cataract.
AB  - PURPOSE: To investigate whether dietary supplementation with IH636 grape seed
      proanthocyanidin extract (GSPE) prevents selenite-induced cataract. SETTING:
      Department of Ophthalmology, Gulhane Military Medical Academy, Ankara, Turkey.
      METHODS: Thirty Spraque-Dawley rat litters were put randomly into 3 groups. In
      group 1 (n = 10), sodium selenite (30 nmol/g body weight) was injected
      subcutaneously on postpartum day 10. In group 2 (n = 10), sodium selenite (30
      nmol/g body weight) was injected on postpartum day 10 and oral GSPE (100 mg/kg
      body weight) was given for 1 week after sodium selenite injection. Only
      subcutaneous saline was injected in group 3 (control, n = 10). The development of
      cataract was assessed for 3 weeks, and its density was graded and photographed
      with a slitlamp. Removed rat lenses were analyzed for glutathione (GSH) and
      malondialdehyde (MDA). RESULTS: All of the rats in group 1 had cataract between
      stage 6 and stage 3. In group 2, only 5 of 10 eyes had cataract between stage 3
      and stage 2 and no cataract occurred in the remaining 5 rats. The difference
      between mean cataract stages in group 1 and group 2 was significant (P<.05). The
      mean GSH level in group 1 was significantly lower than in group 2 and controls
      (P<.05). The mean MDA level in group 1 was significantly higher than in group 2
      and controls (P<.05). CONCLUSIONS: IH636 grape seed proanthocyanidin extract
      effectively suppressed cataract formation in rats. Routine consumption of grape
      seed proanthocyanidin extract in the form of food or dietary supplement may offer
      a prophylactic measure against onset and progression of cataract.

PMID- 16814069
TI  - Stability of the laser in situ keratomileusis corneal flap in rabbit eyes.
AB  - PURPOSE: To quantify the force required to dislodge a laser in situ
      keratomileusis (LASIK) corneal flap in rabbits and correlate that force with
      sources of injury to LASIK corneal flaps in humans. SETTING: Animal Vivarium and
      Department of Ophthalmology, Naval Medical Center, San Diego, California, USA.
      METHODS: Corneal flaps were cut in 56 eyes of 30 rabbits. A -8.00 diopter excimer
      ablation was also performed in 32 of the eyes. Injury testing, using a burst of
      CO2 from a modified paintball gun, was conducted from 1 to 9 days
      postoperatively. Impact force was compared to that generated by mechanical trauma
      (fingers and a small tree branch) striking a force gauge. RESULTS: Of 43 eyes
      tested for injury, flaps could not be dislocated in 11 eyes (26%). There was no
      significant difference between eyes treated with flap only and those that also
      had ablation. When flaps were dislodged, the required force generally resulted in
      extensive intraocular injury. There was no significant difference between the
      force required for flap dislocation on postoperative days 1 and 9. CONCLUSIONS:
      In rabbits, LASIK corneal flaps were very resistant to high-speed wind trauma as
      early as 24 hours postoperatively. Flap stability was robust prior to the
      formation of collagen scar tissue, probably due to epithelial bridging at the
      edge of the flap and an osmotic gradient across the flap-stromal bed interface.
      Although this study used a rabbit model, it seems likely that both these flap
      adhesion mechanisms would also provide stability to the LASIK flap in humans.

PMID- 16814070
TI  - Nanophthalmos: ultrasound biomicroscopy and Pentacam assessment of angle
      structures before and after cataract surgery.
AB  - We report a case of nanophthalmos with intractable secondary glaucoma. Bilateral
      cataract extraction with intraocular lens implantation was used as definitive
      treatment for the chronic angle-closure glaucoma. The changes in angle and
      ciliary body anatomy were well documented with preoperative and postoperative
      Pentacam assessment (Oculus Optikgerate GmbH) and ultrasound biomicroscopy
      (Paradigm Medical Industries) images. We believe these are the first diagnostic
      and prognostic images of this kind in a nanophthalmic eye.

PMID- 16814071
TI  - Intraocular lens pupillary capture after neodymium:YAG laser treatment of
      interlenticular opacification of posterior chamber piggyback intraocular lenses.
AB  - A hyperopic 73-year-old woman had bilateral phacoemulsification with primary
      implantation of piggyback AcrySof intraocular lenses (IOLs) (Alcon) in the
      capsular bag. Interlenticular opacification (ILO) developed after 6 months in the
      left eye and after 2 years in the right eye. Treatment of the ILO in the left eye
      with a neodymium:YAG (Nd:YAG) laser resulted in pupillary capture of the optic of
      the anterior IOL. This case shows that despite using low energy levels, pupillary
      capture of the anterior IOL can occur after Nd:YAG laser treatment for ILO in
      piggyback IOLs.

PMID- 16814072
TI  - Mycobacterium chelonae keratitis after laser-assisted subepithelial keratectomy.
AB  - A 24-year-old man with myopic astigmatism had uncomplicated laser-assisted
      subepithelial keratectomy (LASEK) in October 2004. Approximately 4 weeks later, a
      foreign-body sensation and redness developed in the left eye. A paracentral
      anterior stromal infiltrate was observed, and Gram stain on the day of
      presentation showed branching filamentous gram-positive rods. Cultures
      subsequently grew Mycobacterium chelonae. Topical tobramycin 15 mg/mL,
      azithromycin 2 mg/mL, amikacin 25 mg/mL, and cefazolin 50 mg/mL were initiated
      based on Gram stain results. We believe this is the first documented case of M
      chelonae keratitis after LASEK.

PMID- 16814073
TI  - Bilateral ring scotomas following laser in situ keratomileusis.
AB  - A 53-year-old white man who had a history of transient ocular hypertension had
      bilateral laser in situ keratomileusis (LASIK) for myopia. Subsequent
      computerized static perimetry revealed bilateral, persistent, repeatable
      midperipheral ring scotomas. The pre-LASIK visual fields were within normal
      limits, and the optic discs appeared stable and not diagnostic for glaucomatous
      optic neuropathy. A comprehensive baseline data set before laser refractive
      surgery aids subsequent assessment of individuals at high risk for developing
      glaucoma.

PMID- 16814074
TI  - Surgical management of acute angle-closure glaucoma after toric implantable
      contact lens implantation.
AB  - A case of pupillary block after implantation of an implantable contact lens (ICL)
      is reported, and surgical management and prevention are discussed. In a myopic
      patient, the best corrected visual acuity in the right eye was 20/50 with -15.50 
      3.00 x 175. After uneventful implantation of an ICL, painful acute glaucoma
      developed with an intraocular pressure beyond measurable values. Apparent
      anterior vaulting of the ICL suggested a sizing problem. In a situation of a mid
      wide dilated pupil, immediate explantation of the ICL was performed. Then, using
      a preoperative iris photography as guidance, an anterior chamber iris-claw toric
      phakic intraocular lens was implanted. On postoperative examination, the anterior
      chamber was deep, the angle open, the natural lens clear, and uncorrected visual
      acuity was 20/40.

PMID- 16814075
TI  - Risk for posterior capsule rupture after vitreoretinal surgery.

PMID- 16814076
TI  - Intraoperative fracture of AMO Tecnis (silicone) foldable intraocular lens.

PMID- 16814077
TI  - A systematic review of the use of the ketogenic diet in childhood epilepsy.
AB  - The ketogenic diet has been used in the treatment of intractable childhood
      epilepsy since the 1920s. A systematic review of the efficacy, adverse reactions,
      and costs associated with using the diet was performed. PubMed and Ovid searches
      were performed using the keywords epilepsy/therapy, dietary therapy, ketogenic
      diet, adverse events, and costs. Cochrane library was searched. Bibliographies of
      papers located by searches and review articles were compiled. Papers published
      after 1990 were selected if they were written in either English or French and
      reported on the use of classic ketogenic diet in patients under age 18 years of
      age with medically refractory epilepsy. Outcome measures were degree of seizure
      control, duration patient remained on diet, and occurrence of adverse events.
      Twenty-six studies were found. No prospective-controlled studies were found.
      Fourteen studies met all criteria for inclusion. The studies indicated that some
      children report reduction in seizure frequency. The estimated rate for obtaining
      complete seizure control was 15.6% (95% confidence interval 10.4-20.8%) with 33%
      (95% confidence interval 24.3-41.8%) reporting greater than 50% reduction in
      seizures. Adverse events were not frequent; however, 16 cases of death occurring
      while on the diet were found. No cost/benefit studies were located. There is
      evidence to support the cautious use of ketogenic diet in children with
      refractory epilepsy.

PMID- 16814078
TI  - Plasma levels of antiepileptic drugs in children on the ketogenic diet.
AB  - Influence of the ketogenic diet on plasma concentrations of antiepileptic drugs
      was investigated in an open clinical study of 51 children (mean age 6.6 years)
      with medically refractory epilepsy. The plasma levels of concomitantly used
      antiepileptic drugs were determined immediately before and 3 months after
      initiating the ketogenic diet. To compensate for adjustments in dosing, the
      plasma concentration in relation to the dose per kilogram of body weight per day,
      i.e. the level-to-dose ratio, was used for comparison; it was calculated as the
      plasma concentration (micromol/L) divided by the corresponding weight-normalized
      dose (mg/kg body weight/day) for each drug and child. The level-to-dose ratios of
      each drug before and during the diet were compared. No significant changes in
      these ratios could be found for valproic acid, lamotrigine, topiramate,
      clonazepam, or phenobarbital. In 16 children, the ratio of the free unbound
      concentration of valproic acid to its total plasma concentration was compared
      before and during the diet, but it did not change significantly. Thus, the
      ketogenic diet did not change the plasma concentrations of commonly used
      antiepileptic drugs in children in any significant way. Therefore, when
      initiating the diet, it does not seem necessary to adjust drug doses due to
      pharmacokinetic interactions.

PMID- 16814079
TI  - Electrodiagnostic pattern approach for childhood polyneuropathies.
AB  - Electrophysiologic studies play a key role in the detection and characterization
      of the pattern in childhood polyneuropathies. In this study, the etiologic
      profile of 74 children with polyneuropathy was prospectively evaluated based on
      the electrophysiologic studies. Five electrodiagnostic patterns were identified
      in the cohort: (1) acute axonal polyneuropathy (n: 32, 43%); (2) chronic axonal
      polyneuropathy (n: 16, 22%); (3) demyelinating motor and sensory polyneuropathy
      (n: 13, 17%); (4) pure sensory polyneuropathy (n: 11, 15%); (5) high-low syndrome
      (n: 2, 3%). Etiologic factors were identified in all of the patients with three
      electrodiagnostic patterns of polyneuropathy: acute axonal, pure sensory, and
      high-low syndrome. However, etiologic factors could not be determined in 5 (31%)
      children with chronic axonal polyneuropathy and in 3 (23%) children with
      demyelinating sensory and motor polyneuropathy. Among children with the acute
      axonal pattern, toxic causes were evident in 18 (56%), acute motor axonal
      neuropathy in 11 (35%), and acute motor sensory axonal polyneuropathy in 3 (9%).
      Nine (82%) patients with pure sensory polyneuropathy had diabetes mellitus. In
      conclusion, a thorough history and physical examination in conjunction with
      specific electrodiagnostic patterns might provide a cost-effective and rational
      differential diagnosis of childhood polyneuropathies.

PMID- 16814080
TI  - Parental attitude of mothers, iron deficiency anemia, and breath-holding spells.
AB  - The aim of this study was to investigate the effect of family structure and the
      attitude of mothers on the development of breath-holding spells. The data of the
      Sociodemographic and Parental Attitude Research Instruments of 30 mothers of
      children with breath-holding spells and of 30 mothers of healthy children were
      compared. The subjects were also evaluated for iron deficiency anemia and by age
      related developmental test. No significant difference was observed between the
      two groups in the results of the Sociodemographic and Parental Attitude Research
      Instruments. Iron deficiency anemia was found to be significantly higher in the
      group of mothers of children with breath-holding spells compared with the control
      group. This study suggests that iron deficiency anemia rather than behavioral or
      psychosocial problems of mothers plays a role in the development of breath
      holding spells.

PMID- 16814081
TI  - Congenital perisylvian syndrome: MRI and glucose PET correlations.
AB  - Congenital perisylvian syndromes are late migration/cortical organization
      disorders associated with distinctive clinical and imaging features. The
      clinical, magnetic resonance imaging, and 2-deoxy-2-[18F] fluoro-D-glucose (FDG)
      positron emission tomography scan findings of six children (age range: 3.2-16.7
      years; 5 males) with congenital perisylvian syndrome were evaluated. The patients
      presented with heterogenous neurologic impairments, depending upon the involved
      hemisphere and the extension of perisylvian malformation. Two manifested
      bilateral malformation and four manifested unilateral. The characteristic MRI
      finding consisting of a vertically oriented sylvian fissure continuous with the
      central and postcentral sulcus was associated with variable extension of
      bordering polymicrogyric cortex. The positron emission tomography scans of all
      patients revealed perisylvian metabolic abnormalities corresponding to the
      magnetic resonance imaging-defined abnormality. Variable extent of abnormal
      glucose metabolism was also observed in areas with normal magnetic resonance
      imaging features. All patients with unilateral magnetic resonance imaging
      abnormality exhibited abnormal glucose metabolism also in the contralateral side.
      The two patients with bilateral malformation had more extensive positron emission
      tomography abnormalities than the morphologic anomalies on MRI. Although MRI
      remains the diagnostic gold standard to detect the lesion, positron emission
      tomography scan is helpful to evaluate the full functional extension of the
      cortical anomaly, thereby contributing to the definition of the clinical severity
      of the syndrome.

PMID- 16814082
TI  - Coenzyme Q10 absorption and tolerance in children with Down syndrome: a dose
      ranging trial.
AB  - Controlled studies of coenzyme Q(10) dosing and tolerance have been reported in
      adults, but not in pediatric patients. This study compares low- and high-dose
      coenzyme Q(10) (LiQ-NOL syrup) absorption and tolerance in children with Down
      syndrome. After a 1-month low-dose (1.0 mg/kg/day) run-in period, all
      participants received high-dose coenzyme Q(10) (10.0 mg/kg/day) for two
      additional months (in randomized sequence as one daily dose or split into two
      daily doses). Chemistry profiles and complete blood counts were determined just
      before and at the study completion. Plasma coenzyme Q(10) concentrations were
      determined initially and at each study visit. Parents reported adverse events and
      study drug evaluations using standardized forms. Most of the 16 children who
      completed this study tolerated high-dose coenzyme Q(10) well. Uncooperative
      behavior resulted in premature withdrawal of two participants, and may have been
      treatment-related. Pre- and posttreatment laboratory test changes were considered
      to be clinically nonsignificant. Study results indicate that high-dose coenzyme
      Q(10) (10 mg/kg/day) is well-absorbed and well-tolerated by most children with
      Down syndrome, and appears to provide plasma concentrations which are comparable
      to previous adult studies administering much higher coenzyme Q(10) dosages.

PMID- 16814083
TI  - Enhanced capacity of epilepsy in brain malformation produced during early
      development.
AB  - This study investigates the clinical features of epilepsy in 20 patients with
      brain malformation. Epileptic seizures were recognized in 15 patients, 12 of whom
      had their first seizure by 1 year of age. Partial seizure was the initial seizure
      type in 10 patients. Epileptic seizures were controlled in only four patients.
      Patients with holoprosencephaly and lissencephaly had seizure onset by 3 months
      of age, resulting in the most severe neurologic outcome. Only two patients with
      porencephaly had epileptic seizures, and in one of those patients the seizures
      were well controlled. A wide variety of clinical features of epilepsy in patients
      with brain malformation was found. More immature anomalous brain lesions may be
      associated with an enhanced capacity of epilepsy and resultant refractory
      seizures.

PMID- 16814085
TI  - In memoriam: Manuel Rodriguez Gomez, MD July 4, 1928 - January 21, 2006.

PMID- 16814084
TI  - Deletion of 17p13 and LIS1 gene mutation in isolated lissencephaly sequence.
AB  - Classical lissencephaly is a neuroblast migration disorder that occurs either as
      isolated lissencephaly sequence or in association with malformation syndromes,
      such as the Miller-Dieker syndrome. In this work, alterations of the LIS1 gene in
      patients diagnosed as having isolated lissencephaly sequence were investigated.
      Ten patients were evaluated for the following aspects: classical cytogenetics by
      karyotyping using solid staining and G-banding; molecular cytogenetics using
      fluorescent in situ hybridization with a specific probe for the critical region
      of isolated lissencephaly sequence; and molecular analysis using deoxyribonucleic
      acid sequencing. Classical cytogenetic analysis indicated apparently normal
      karyotypes in all patients, but fluorescent in situ hybridization revealed a
      17p13.3 microdeletion in one. In another patient, deoxyribonucleic acid
      sequencing disclosed a 1 base pair insertion in exon 4 within a sequence of eight
      consecutive adenine residues (162-163insA), a mutation that predicts a truncated
      protein. Two different polymorphisms were also detected: a T>C substitution in
      intron 6 (c.568 + 27bp T>C) and a C>T substitution in the nontranslated region of
      exon 11 (1250 C>T). These results indicate that cytogenetic analysis and
      molecular investigation of the LIS1 gene are not always sufficient to determine
      the disease etiology. These findings are consistent with previous studies and
      suggest the involvement of other genes in cortical malformation.

PMID- 16814086
TI  - Homozygous MTHFR C677T gene mutation and recurrent stroke in an infant.
AB  - The role of homozygosity for the C677T mutation in the 5,10
      methylenetetrahydrofolate reductase (MTHFR) gene as an independent risk factor
      for primary and recurrent stroke has been questioned, although recent data appear
      to be supportive. However, the association of homozygous C677T MTHFR mutation
      with silent brain infarctions in infancy has not been reported. The authors
      describe an 11-month-old male who had suffered a silent brain infarction followed
      by a symptomatic arterial stroke. The evaluation revealed mildly elevated
      homocysteine levels secondary to homozygous C677T alleles for MTHFR and iron
      deficiency anemia. An extensive evaluation for other causes of infarction was
      negative. We suggest that the mother's homozygous MTHFR status played a role in
      the early onset of stroke and that iron deficiency anemia may have contributed to
      the recurrence. The patient was treated with anticoagulation therapy, folic acid,
      and iron supplementation and has not had a recurrent event during 3 years of
      follow-up. This case provides further evidence that homozygous MTHFR mutation is
      a predisposing factor for early and recurrent pediatric stroke, including silent
      infarcts, especially in the presence of other risk factors.

PMID- 16814087
TI  - Early continuous video-EEG in acute near-total intrauterine asphyxia.
AB  - The evolution of electroencephalographic changes after acute hypoxic-ischemic
      injury is poorly understood, as a clear time of insult is often absent and
      continuous electroencephalographic monitoring in the first 3 days after such
      injury has not been previously reported. Infants who suffer sudden profound
      asphyxia, often termed "acute near-total intrauterine asphyxia", have evidence of
      damage to the deep gray matter. In these infants it is possible to time the onset
      and duration of cerebral ischemia. This report describes early continuous video
      electroencephalography from 3 hours after birth in an infant with the
      characteristic clinical and radiologic features of acute near-total intrauterine
      asphyxia.

PMID- 16814088
TI  - Chronic herpes simplex virus encephalitis in childhood.
AB  - Although herpes simplex virus is a major cause of acute encephalitis in
      childhood, chronic herpes simplex virus encephalitis has only rarely been
      reported. This report presents a case of chronic herpes simplex virus
      encephalitis in a 6-year-old female. Diagnosis was based on the detection of
      herpes simplex virus deoxyribonucleic acid by polymerase chain reaction in
      combination with the cerebrospinal fluid/serum ratio of herpes simplex virus
      specific immunoglobulin G, the presence of herpes simplex virus-specific
      oligoclonal immunoglobulin G bands in cerebrospinal fluid, and calcifications in
      the temporal regions found on cerebral computed tomographic scan. Prolonged
      antiviral therapy was beneficial to later mental development.

PMID- 16814089
TI  - West Nile encephalitis mimicking herpes encephalitis.
AB  - A male with a febrile illness, altered consciousness, and seizures was diagnosed
      with meningoencephalitis. The suspected etiology was herpes simplex virus on the
      basis of a focal seizure at presentation, and he was treated with acyclovir until
      this pathogen was excluded. The patient made a complete recovery. Because of a
      West Nile fever epidemic in Israel at the time, serology tests for West Nile
      virus were performed; results were positive. This case highlights the diagnostic
      problems in West Nile fever. The literature is discussed in brief.

PMID- 16814090
TI  - Vanishing white matter disease with periodic (paroxysmal) hemiparesis.
AB  - Vanishing white matter disease is a chronically progressive leukodystrophy with
      periods of acute deterioration after head trauma and febrile illness. This report
      describes a child with genetically and clinically confirmed vanishing white
      matter disease exhibiting frequent episodes of right-sided hemiplegia, aphasia,
      and headache resolving fully within hours to days. This report describes a case
      of this condition presenting with episodes of hemiparesis with full discovery to
      baseline. Some possible mechanisms explaining this unusual presentation are
      provided.

PMID- 16814091
TI  - Partial epilepsy and 47,XXX karyotype: report of four cases.
AB  - Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome
      abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of
      the most common sex chromosome abnormalities in females, and is associated with
      considerable phenotypic variability. This report describes four 47,XXX females
      with mental deficiency and epilepsy. Although a specific electro-clinical pattern
      could not be defined, the epileptic phenotypes of these patients share many
      features; we suggest that the association 47,XXX/epilepsy/mental retardation may
      not be coincidental. This report also enlarges the clinical spectrum of the
      47,XXX phenotype. Moreover, these observations highlight the critical role of
      chromosome X in epilepsy and mental retardation.

PMID- 16814092
TI  - Perinatal stroke in twins without co-twin demise.
AB  - Perinatal stroke in twins without co-twin demise has not been well-described. In
      this study, the International Classification of Diseases- 9th edition code
      searches and medical record review were used to identify all children with
      arterial ischemic stroke examined in a pediatric stroke clinic over a 2-year
      period. Four of the 35 children (11.4%) with perinatal arterial ischemic stroke
      were twins; none had co-twin demise. No co-twin had any clinical evidence of
      perinatal stroke. The most common findings on prothrombotic evaluation were
      elevated antiphospholipid antibodies (2), elevated lipoprotein a (2), and
      elevated Factor VIIIc (2). Twin gestation without co-twin demise may be a risk
      factor for perinatal stroke, and might help explain the higher incidence of
      cerebral palsy in twins.

PMID- 16814093
TI  - Orbitofrontal seizures presenting with ictal visual hallucinations and interictal
      psychosis.
AB  - Hallucinations are commonly believed to reflect temporal lobe dysfunction. This
      report presents the clinical, electroencephalographic, and neuroimaging findings
      in an 8-year-old male who experienced the acute onset of ictal auditory and
      visual hallucinations associated with epileptic activation of the right
      orbitofrontal region. Right frontal lobe surgery resulted in seizure freedom and
      disappearance of his psychotic symptoms. Histologic tissue examination revealed
      non-balloon cell Taylor type cortical dysplasia.

PMID- 16814094
TI  - Cataplexy leading to the diagnosis of Niemann-Pick disease type C.
AB  - Cataplexy in childhood is a rare and often misdiagnosed symptom. It is described
      as a brief episode of bilateral loss of muscle tone with intact consciousness,
      triggered by a variety of strong emotions and in particular with unexpected
      laughter. This report presents a 9-year old male with progressive cerebellar and
      pyramidal symptoms and a cognitive decline since the age of 4. His recently
      developed "drop attacks" on laughter were recognized as cataplexy and led to the
      diagnosis of Niemann-Pick type C disease. With biochemical studies this
      diagnosis, a lysosomal storage disease, was confirmed. With cataplexy narcolepsy,
      Niemann-Pick type C disease, Norrie disease, Prader-Willi syndrome, and Coffin
      Lowry syndrome are associated disorders. Recognition of cataplexy in children
      with concomitant neurologic symptoms may lead to an early and straight diagnosis
      of one of these disorders.

PMID- 16814095
TI  - Diabetes, glucose toxicity, and oxidative stress: A case of double jeopardy for
      the pancreatic islet beta cell.
AB  - Diabetes is commonly referred to in terms of type 1 and type 2. Both forms
      involve pancreatic islet beta-cell abnormalities, characterized by death in type
      1 and accelerated apoptosis in type 2. The resultant chronic hyperglycemia leads
      to chronic oxidative stress for all tissues because glucose in abnormally high
      concentrations forms reactive oxygen species. It has been repeatedly emphasized
      that this can lead to oxidative damage in the classical secondary targets of
      diabetes, such as eyes, kidneys, nerves, and blood vessels. However, it has been
      much less appreciated that the beta cell itself is also a prime target, a case of
      double jeopardy. This situation is all the more pernicious because islets contain
      among the lowest levels of antioxidant enzyme activities compared to other
      tissues. This adverse effect of high glucose concentrations is referred to as
      glucose toxicity. A major manifestation of glucose toxicity in the beta cell is
      defective insulin gene expression, diminished insulin content, and defective
      insulin secretion. The molecular mechanisms involve the development of decreased
      levels of two very important insulin promoter transcription factors, PDX-1 and
      MafA. Studies with animal models of type 2 diabetes have established that
      pharmacologic protection against oxidative stress ameliorates the severity of
      diabetes progression. Translational research with humans is now under way to
      ascertain whether this protection can be provided to patients experiencing
      inadequate glycemic control.

PMID- 16814096
TI  - Nox is playing with a full deck in vascular smooth muscle, a commentary on "Noxa1
      is a central component of the smooth muscle NADPH oxidase in mice".

PMID- 16814097
TI  - Amyloid-beta, BACE, and oxidative stress in Alzheimer's disease, a commentary on
      "The different aggregation state of beta-amyloid 1-42 mediates different effects
      on oxidative stress, neurodegeneration and BACE-1 expression".

PMID- 16814098
TI  - ROS and kidney disease in the evolution from acute phase to chronic end stage
      disease: A commentary on "Oxidative signaling in renal epithelium: Critical role
      of cPLA2 and p38SAPK".

PMID- 16814099
TI  - Noxa1 is a central component of the smooth muscle NADPH oxidase in mice.
AB  - NADPH oxidase is the most important source of oxygen-derived radicals (ROS) in
      the vascular wall. In vascular smooth muscle cells (VSMC), NADPH oxidase is
      characterized by the expression of the membrane subunit Nox1, which is activated
      by cytoplasmic proteins binding to its activation domain. We set out to identify
      the cytoplasmic protein involved in NADPH oxidase activation in mouse VSMC.
      Western blot analysis revealed that human endothelial cells and leukocytes but
      not VSMC from the aorta of the rat and the mouse express the classic NADPH
      oxidase activator p67phox. In mouse VSMC, however, the p67phox homologue Noxa1
      was detected. Using antibodies generated against mouse Noxa1, the protein was
      observed in the cytosolic fraction of mouse VSMC with a molecular weight of about
      51 kDa. Immunohistochemistry revealed that Noxa1 is expressed in the smooth
      muscle layer but not in endothelium or the adventitia of the mouse carotid
      artery. Fluorescent fusion proteins of Noxa1 were observed to be expressed in the
      cytoplasm of VSMC and coexpression of the NADPH oxidase organizer Noxo1 targeted
      the complex to membrane. An antisense plasmid of Noxa1 attenuated the endogenous
      Noxa1 protein expression in VSMC. This plasmid attenuated the ROS formation in
      mouse VSMC as detected using L012 chemiluminescence and prevented the agonist
      induced ROS production in response to basic fibroblast growth factor and
      epidermal growth factor. In conclusion, these data indicate that Noxa1 replaces
      p67phox in VSMC and plays a central role in the activation of the NADPH oxidase
      in the vascular wall.

PMID- 16814100
TI  - The various aggregation states of beta-amyloid 1-42 mediate different effects on
      oxidative stress, neurodegeneration, and BACE-1 expression.
AB  - The amyloid cascade hypothesis suggests that the insoluble and fibrillar form of
      beta-amyloid (A beta) may play a primary pathogenic role in Alzheimer disease at
      the molecular level. However, neither the rate of dementia nor the extent of
      neuronal change seems to correlate with the levels of amyloidotic plaques (i.e.,
      aggregated/fibrillar A beta). Recent evidence suggests, however, that
      neurotoxicity may be exerted also by rather small soluble aggregates of A beta,
      including oligomers. To characterize the mechanisms underlying toxicity mediated
      by the various aggregation states of A beta peptides is then a major goal of
      research. In this work we investigated the effects of fibrillar, prefibrillar,
      and oligomeric A beta(1-42) on the induction of oxidative stress, cell death, and
      BACE-1 expression in NT2 neuronal cells. We found that prefibrillar and
      oligomeric A beta(1-42) resulted in a more dramatic increase in the oxidative
      stress markers 4-hydroxynonenal and hydrogen peroxide compared to fibrillar A
      beta(1-42). Moreover, increased oxidative stress levels also resulted in a more
      rapid and significant induction of both apoptotic and necrotic neuronal cell
      death. Accordingly, fibrillar A beta(1-42), but not the soluble nonfibrillar
      forms, was the only condition able to up-regulate BACE-1 expression and activity.

PMID- 16814101
TI  - Oxidative signaling in renal epithelium: Critical role of cytosolic phospholipase
      A2 and p38(SAPK).
AB  - Previous studies from this laboratory have demonstrated a critical role of
      cytosolic phospholipase A2 (cPLA2) and arachidonic acid in angiotensin II (Ang
      II) AT2 receptor-mediated signal transduction in renal epithelium. In primary
      proximal tubular epithelial cells exposed to hydrogen peroxide (H2O2), both the
      selective cPLA2 inhibitors and the cPLA2 antisense oligonucleotides significantly
      attenuated H2O2-induced arachidonic acid liberation and activation of p38(SAPK),
      ERK1/2, and Akt1. This H2O2-induced kinase activation was significantly
      attenuated by a Src kinase inhibitor PP2, or by transient transfection of
      carboxyl-terminal Src kinase (CSK) that maintained Src in the dormant form. Under
      basal conditions, Src coimmunoprecipitated with epidermal growth factor receptor
      (EGFR), while H2O2 increased EGFR phosphorylation in the complex. We observed
      that inhibition of EGFR kinase activity with AG1478 significantly attenuated H2O2
      induced p38(SAPK) and ERK1/2 activation, but did not inhibit Akt1 activation.
      Furthermore, it seems that p38(SAPK) is upstream of ERK1/2 and Akt1, since a
      p38(SAPK) inhibitor SB203580 significantly blocked H2O2-induced activation of
      ERK1/2 and Akt1. Interestingly, overexpression of the dominant-negative p38(SAPK)
      isoform alpha inhibited ERK1/2 but not Akt1 activation. Our observations
      demonstrate that in these nontransformed cells, activation of cPLA2 is a
      converging point for oxidative stress and Ang II, which share common downstream
      signaling mechanisms including Src and EGFR. In addition, p38(SAPK) provides a
      positive input to both growth and antiapoptotic signaling pathways induced by
      acute oxidative stress.

PMID- 16814102
TI  - Zinc supplementation decreases the development of atherosclerosis in rabbits.
AB  - Developing atherosclerotic plaques in cholesterol-fed rabbits are enriched in
      iron but depleted in zinc. In order to examine further the role of zinc, New
      Zealand White rabbits were fed a high-cholesterol 1% (w/w) diet with zinc (1
      g/kg) supplementation for 8 weeks. After the 8-week period, the average
      atherosclerotic lesion cross-sectional areas in the aortas of the animals fed
      with the zinc supplement were significantly decreased (1.0 mm2) compared with
      lesion areas of the animals fed only on the high-cholesterol diet (3.1 mm2).
      Using nuclear microscopy, a technique for mapping and measuring trace elements in
      tissue sections, lesion zinc levels (24 ppm) were observed to be unchanged in the
      zinc-fed rabbits compared to controls. However, average lesion Fe levels in the
      zinc-fed group were measured at 32 ppm, whereas in the control group the average
      Fe levels were significantly higher at 43 ppm (P = 0.03). Our data support the
      concept that zinc may have an antiatherogenic effect by decreasing iron levels in
      the lesion, possibly leading to inhibition of iron-catalyzed free radical
      reactions.

PMID- 16814104
TI  - Contribution of peroxidized cardiolipin to inactivation of bovine heart
      cytochrome c oxidase.
AB  - The lipid-soluble peroxides, tert-butyl hydroperoxide and peroxidized
      cardiolipin, each react with bovine cytochrome c oxidase and cause a loss of
      electron-transport activity. Coinciding with loss of activity is oxidation of
      Trp19 and Trp48 within subunits VIIc and IV, and partial dissociation of subunits
      VIa and VIIa. tert-Butyl hydroperoxide initiates these structural and functional
      changes of cytochrome c oxidase by three mechanisms: (1) radical generation at
      the binuclear center; (2) direct oxidation of Trp19 and Trp48; and (3)
      peroxidation of bound cardiolipin. All three mechanisms contribute to
      inactivation since blocking a single mechanism only partially prevents oxidative
      damage. The first mechanism is similar to that described for hydrogen peroxide
      [Biochemistry43:1003-1009; 2004], while the second and third mechanism are unique
      to organic hydroperoxides. Peroxidized cardiolipin inactivates cytochrome c
      oxidase in the absence of tert-butyl hydroperoxide and oxidizes the same
      tryptophans within the nuclear-encoded subunits. Peroxidized cardiolipin also
      inactivates cardiolipin-free cytochrome c oxidase rather than restoring full
      activity. Cardiolipin-free cytochrome c oxidase, although it does not contain
      cardiolipin, is still inactivated by tert-butyl hydroperoxide, indicating that
      the other oxidation products contribute to the inactivation of cytochrome c
      oxidase. We conclude that both peroxidized cardiolipin and tert-butyl
      hydroperoxide react with and triggers a cascade of structural alterations within
      cytochrome c oxidase. The summation of these events leads to cytochrome c oxidase
      inactivation.

PMID- 16814103
TI  - Overexpression of manganese or copper-zinc superoxide dismutase inhibits breast
      cancer growth.
AB  - We have studied the effects of overexpression of superoxide dismutase (SOD), a
      tumor suppressor protein that dismutes superoxide radical to H2O2, on breast
      cancer cell growth in vitro and xenograft growth in vivo. No previous work has
      directly compared the growth-suppressive effects of manganese SOD (MnSOD) and
      copper-zinc SOD (CuZnSOD). We hypothesized that either adenoviral MnSOD (AdMnSOD)
      or adenoviral CuZnSOD (AdCuZnSOD) gene therapy would suppress the growth of human
      breast cancer cells. After determining the antioxidant profiles of three human
      breast cell lines, MCF 10A, MDA-MB231, and MCF-7, we measured the effects of
      MnSOD or CuZnSOD overexpression on cell growth and survival in vitro and in vivo.
      Results demonstrated that infection with AdMnSOD or AdCuZnSOD increased the
      activity of the respective enzyme in all three cell lines. In vitro,
      overexpression of MnSOD or CuZnSOD decreased not only cell growth but also
      clonogenic survival in a dose- and transgene-dependent manner. In vivo, treatment
      of tumors with AdMnSOD or AdCuZnSOD decreased xenograft growth compared to
      controls. The first direct comparison of MnSOD to CuZnSOD overexpression
      indicated that CuZnSOD and MnSOD were similarly effective at suppressing cancer
      cell growth.

PMID- 16814105
TI  - Regulation of heme oxygenase-1 gene expression through the phosphatidylinositol 3
      kinase/PKC-zeta pathway and Sp1.
AB  - The molecular mechanisms involved in modulation of the antioxidant cell defence
      by survival signals remain largely unexplored. Here, we report a mechanistic
      connection between the survival signal elicited by nerve growth factor (NGF) and
      the antioxidant cell defence represented by heme oxygenase-1 (HO-1) at the level
      of a newly identified Sp1 site in the human ho1 proximal promoter. By using
      luciferase reporter constructs we identified a PI3K-responsive region containing
      a GC-box that resembled the response element for Sp1. Indeed, transfection of Sp1
      deficient SL2 cells, electrophoretic mobility shift assays, the use of the GC-box
      binding drug mithramycin, and mutation of the GC-box provided evidence for a Sp1
      like site in the PI3K-sensitive region. Then, we observed with the use of a Sp1
      Gal4 chimera that PI3K regulates the transactivating capacity of Sp1.
      Cotransfection of active PI3K and PKC-zeta expression vectors resulted in
      substantial increase of Sp1 phosphorylation and in synergistic activation of both
      Sp1-Gal4 and endogenous Sp1. Moreover, these effects were mimicked by
      cotransfection of active MEK and ERK expression vectors and were blocked by the
      MEK inhibitor PD98059. Inhibition of HO-1 with Sn protoporphyrin IX and blockage
      of Sp-1-mediatied upregulation of HO-1 with mithramycin attenuated antioxidant
      and cytoprotective functions of NGF against hydrogen peroxide. This study
      elucidates how NGF contributes to protection of target cells against oxidative
      stress.

PMID- 16814106
TI  - Mitochondrial defects and oxidative damage in patients with peripheral arterial
      disease.
AB  - Abnormal mitochondrial function is present in patients with peripheral arterial
      disease and may contribute to its clinical manifestations. However, the specific
      biochemical mitochondrial defects and their association with increased oxidative
      stress have not been fully characterized. Gastrocnemius muscle was obtained from
      peripheral arterial disease patients (n = 25) and age-matched controls (n = 16)
      and mitochondrial parameters were measured. Complexes I through IV of the
      electron transport chain were individually evaluated to assess for isolated
      defects. Muscle was also evaluated for protein and lipid oxidative changes by
      measuring the levels of protein carbonyls, lipid hydroperoxides, and total 4
      hydroxy-2-nonenal binding and for the activities of the antioxidant enzymes
      superoxide dismutase, catalase, and glutathione peroxidase. Mitochondrial
      electron transport chain complexes I, III, and IV in arterial disease patients
      demonstrated significant reductions in enzymatic activities and mitochondrial
      respiration compared to controls. Oxidative stress biomarker analysis
      demonstrated significantly increased levels of protein carbonyls, lipid
      hydroperoxides, and 4-hydroxy-2-nonenal compared to control muscle. Antioxidant
      enzyme activities were altered, with a significant decrease in superoxide
      dismutase activity and significant increases in catalase and glutathione
      peroxidase. Peripheral arterial disease is associated with abnormal mitochondrial
      function and evidence of significant oxidative stress.

PMID- 16814107
TI  - Increased oxidative stress is correlated with mitochondrial dysfunction in
      chagasic patients.
AB  - Previously, we have shown in an experimental model of Trypanosoma cruzi infection
      that increased oxidative stress and antioxidant insufficiency are associated with
      myocardial (cellular and mitochondrial) oxidative damage and mitochondrial
      functional decline and might be of pathological significance in Chagas disease.
      In the present study, we investigated whether enhanced oxidative stress and
      mitochondrial functional decline are found in human chagasic patients. Our data
      show substantially higher plasma (two-four-fold) and mitochondrial (67%)
      malonylaldehyde (MDA) levels in chagasic (n = 80, group 2) compared to healthy (n
      = 50, group 1) subjects. Moreover, antioxidant defense was compromised in
      chagasic patients. Hence, we noted a 50% decline in glutathione content and
      losses of 31, 60, and 68% in glutathione peroxidase, superoxide dismutase (SOD),
      and MnSOD activities, respectively, relative to the findings in healthy controls.
      Further, chagasic subjects exhibited decreased mitochondrial respiratory complex
      (CI: 72%; CIII: 71%) activities. Nonchagasic cardiomyopathy subjects (n = 20,
      group 3) exhibited marginally higher plasma MDA levels compared to gp1 subjects
      and were not compromised in plasma antioxidant defense capacity. These data
      suggest that human chagasic patients sustain an antioxidant/oxidant imbalance and
      a mitochondrial decline of respiratory complex activities in the circulatory
      system. A positive correlation between increased MDA levels, MnSOD decline, and
      inhibition of respiratory complexes suggests that oxidative stress may contribute
      to mitochondrial dysfunction in chagasic patients.

PMID- 16814108
TI  - Long-term moderate magnesium-deficient diet shows relationships between blood
      pressure, inflammation and oxidant stress defense in aging rats.
AB  - Epidemiological and experimental studies have indicated a relationship among
      aging, dietary Mg, inflammatory stress, and cardiovascular disease. Our aim in
      the present study was to investigate possible links between dietary Mg, oxidant
      stress parameters, and inflammatory status with aging in rats. We designed a long
      term study in which rats were fed for 22 months with moderately deficient (150
      mg/kg), standard (800 mg/kg), or supplemented (3200 mg/kg) Mg diets. Comparisons
      were made with young rats fed with the same diets for 1 month. Compared to the
      standard and supplemented diets, the Mg-deficient diet significantly increased
      blood pressure, plasma interleukin-6, fibrinogen, and erythrocyte
      lysophosphatidylcholine, particularly in aging rats, it decreased plasma albumin.
      The impairment of redox status was indicated by increases in plasma
      thiobarbituric acid reactive substances and oxysterols and an increased blood
      susceptibility to in vitro free-radical-induced hemolysis. We concluded that Mg
      deficiency induced a chronic impairment of redox status associated with
      inflammation which could significantly contribute to increased oxidized lipids
      and promote hypertension and vascular disorders with aging. Extrapolating to the
      human situation and given that Mg deficiency has been reported to be surprisingly
      common, particularly in the elderly, Mg supplementation might be useful as an
      adjuvant therapy in preventing cardiovascular disease.

PMID- 16814109
TI  - As(III) transcriptionally activates the gadd45a gene via the formation of H2O2.
AB  - Arsenic is a ubiquitous environmental contaminant associated with increased risks
      of human cancers of the skin, lung, bladder, and prostate. Intriguingly, it is
      also used to treat certain types of leukemia. It has recently been suggested that
      these paradoxic effects may be mediated by arsenic's ability to simultaneously
      activate DNA damage and apoptotic and transformation pathways. Here, we
      investigate the effects of arsenic exposure on the induction of the growth arrest
      and DNA damage protein 45 alpha (GADD45 alpha), which is thought to play roles in
      apoptosis, DNA damage response, and cell cycle arrest. We found that arsenic
      transcriptionally activates the gadd45 alpha promoter located in a 153-bp region
      between -234 and -81, relative to the transcriptional start site. In addition,
      this transcriptional induction was abrogated in the presence of H2O2 scavengers,
      suggesting a role for H2O2 in the transcriptional control of the gadd45a gene
      through a Fenton-like free radical mechanism.

PMID- 16814110
TI  - Plasma nitrite reserve and endothelial function in the human forearm circulation.
AB  - Attenuation of endothelium-derived nitric oxide (NO) synthesis is a hallmark of
      endothelial dysfunction. Early detection of this disorder may have therapeutic
      and prognostic implications. Plasma nitrite mirrors acute and chronic changes in
      endothelial NO-synthase activity. We hypothesized that local plasma nitrite
      concentration increases during reactive hyperemia of the forearm, reflecting
      endothelial function. In healthy subjects (n = 11) plasma nitrite and nitrate
      were determined at baseline and during reactive hyperemia of the forearm using
      reductive gas-phase chemiluminescence and flow-injection analysis, respectively.
      Endothelium-dependent dilation of the brachial artery was measured as flow
      mediated dilation (FMD) using high-resolution ultrasound. Results were compared
      to patients with endothelial dysfunction as defined by reduced FMD (n = 11).
      Reactive hyperemia of the forearm increased local plasma nitrite concentration
      from 68 +/- 5 to 126 +/- 13 nmol/L (p < 0.01), whereas in endothelial dysfunction
      nitrite remained unaffected (116 +/- 12 to 104 +/- 10 nmol/L; n.s.),
      corresponding to nitrite reserves of 94 +/- 21 and -8 +/- 4%. This was
      accompanied by a significantly greater increase in brachial artery diameter (FMD:
      8.5 +/- 0.4% vs 2.9 +/- 0.5%, for healthy subjects and endothelial dysfunction,
      respectively; p < 0.001). This observation suggests that nitrite changes reflect
      endothelial function. Assessment of local plasma nitrite during reactive
      hyperemia may open new avenues in the diagnosis of vascular function.

PMID- 16814111
TI  - Selective regulation of hydrogen peroxide signaling by receptor tyrosine
      phosphatase-alpha.
AB  - Reactive oxygen species (ROS) are constantly produced in the human body and are
      involved in the pathogenesis of aging, cardiovascular diseases, and cancer.
      Emerging evidence indicates that oxidation and inhibition of protein tyrosine
      phosphatases (PTPs) are critical for ROS signal transduction. However, the role
      of individual PTPs in ROS signaling remains unclear. Here, we demonstrated that
      the receptor-like PTP alpha (RPTP alpha) was an effector of H2O2, the most stable
      form of ROS. H2O2 at nontoxic concentration rapidly induced the association of
      RPTP alpha with Src family kinases, platelet-derived growth factor receptor-beta,
      and protein kinase D in various cultured cells, although it markedly suppressed
      RPTP alpha phosphorylation on Tyr-789. We further identified that RPTP alpha
      selectively regulated the signal transduction pathways induced by H2O2.
      Particularly, RPTP alpha was required for the activation of protein kinase D and
      for the modulation of p130Cas tyrosine phosphorylation in response to H2O2. In
      contrast, the H2O2-induced inactivation of Src family kinases and suppression of
      paxillin phosphorylation on Tyr-118 were both largely independent of RPTP alpha.
      Our findings indicate that H2O2 signaling pathways are selectively regulated by
      RPTP alpha in cells, which may provide new insights into the functional
      regulation of ROS signal transduction by PTPs.

PMID- 16814112
TI  - NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS), marked by infiltration of monocyte-derived macrophages in the brain
      parenchyma. Macrophages contribute to disease pathology by secretion of
      inflammatory mediators, such as reactive oxygen species (ROS). ROS are involved
      in various processes underlying MS pathology, including monocyte migration across
      the blood-brain barrier, phagocytosis and degradation of myelin, axonal
      degeneration, and oligodendrocyte damage. High concentrations of ROS cause
      oxidative stress, which induces transcriptional activation of phase II
      detoxification enzymes, such as the antioxidant protein NAD(P)H:quinone
      oxidoreductase 1 (NQO1). Since NQO1 expression may act as an indicator of
      oxidative stress and knowledge about the cellular distribution pattern of NQO1 in
      MS brains is lacking, we examined the expression of NQO1 in various well
      characterized MS lesions. Here, we show for the first time that NQO1 is highly
      upregulated in active and chronic active MS lesions, particularly in hypertrophic
      astrocytes and myelin-laden macrophages. We hypothesize that increased NQO1
      expression may reflect an endogenous defense response against ROS-mediated
      cellular toxicity. Compounds that induce the production of endogenous antioxidant
      enzymes, such as NQO1, may be potential targets for future treatment strategies
      in MS.

PMID- 16814113
TI  - Potent antiproliferative effects of resveratrol on human osteosarcoma SJSA1
      cells: Novel cellular mechanisms involving the ERKs/p53 cascade.
AB  - The chemopreventive activity of resveratrol (RSVL) has been demonstrated in
      several types of cancer. However, its effects and the underling mechanisms remain
      poorly understood. In this study, we investigated the involvement of the mitogen
      activated protein kinase (MAPK)/p53 signal transduction mechanism in RSVL-induced
      growth inhibition using a human osteosarcoma cell line. We demonstrate that RSVL
      reduces cell viability and growth of SJSA1 osteosarcoma cells. Morphological
      profiles and 4,6-diamidino-2-phenylindole nuclear staining of RSVL-treated cells
      indicated marked nuclear fragmentation. Cleavage of the (116-kDa) poly(ADP
      ribose) polymerase protein into an 89-kDa fragment (a proapoptotic marker system)
      was substantially augmented by RSVL treatment. RSVL-dependent growth impairment
      was preceded by enhanced phosphorylation of extracellular signal-regulated kinase
      (ERK)1/2 (at Thr202/Tyr204). Likewise, RSVL increased the phosphorylation of p53
      tumor suppressor protein (at Ser15). The effects of RSVL on ERKs and on p53
      phosphorylation were abrogated by either the MAPK inhibitor PD98059 or the p53
      inhibitor pifithrine-alpha. The present study indicates that RSVL
      antiproliferative effects on osteosarcoma cells are mediated by the activation of
      the ERKs/p53 signaling pathway and therefore identifies new targets for
      strategies to treat and/or prevent osteosarcoma.

PMID- 16814114
TI  - Effect of reduced culture temperature on antioxidant defences of mesenchymal stem
      cells.
AB  - Mesenchymal stem cells (MSC) promise to be valuable therapeutic tools but, due to
      their low numbers, require considerable in vitro expansion before use. This leads
      to in vitro aging, the accumulation of intracellular oxidative damage, and
      subsequently a decreased potential for proliferation and differentiation.
      Optimised culture conditions might help to reduce oxidative damage in MSC in
      vitro, and therefore, as reduced temperature is known to reduce oxidative stress
      in other somatic cells, we have investigated the effect of reduced temperature on
      rat MSC viability, differentiation, and oxidative damage. Temperature reduction
      did not affect MSC viability but increased differentiation and reduced apoptosis.
      Oxidative-damage-related indices were improved; reactive oxide species, nitric
      oxide, thiobarbituric acid reactive substances, carbonyl, and lipofuscin levels
      were reduced and glutathione peroxidase and superoxide dimutase levels increased.
      Levels of antiapoptotic heat shock proteins (HSP-27, -70, and -90) were raised
      and levels of the proapoptotic HSP-60 reduced. These data demonstrate that
      culturing MSC at reduced temperature decreases the accumulation of oxidative
      damage and therefore would probably improve long-term viability and successful
      engraftment of MSC used for tissue engineering or cell therapeutic purposes.

PMID- 16814115
TI  - Ultraviolet A sensitivity in Smith-Lemli-Opitz syndrome: Possible involvement of
      cholesta-5,7,9(11)-trien-3 beta-ol.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a severe developmental disorder caused by
      mutations in the DHCR7 gene coding for 7-dehydrocholesterol (7-DHC) reductase,
      the enzyme involved in the last step of cholesterol biosynthesis. SLOS
      homozygotes exhibit marked deficiency of cholesterol in plasma and tissues with
      concomitant increase in 7-DHC. Ultraviolet A (UVA) photosensitivity has been
      recognized as part of SLOS with maximal response occurring at 350 nm. 7-DHC
      itself has no UVA absorption and so cannot be the direct cause of SLOS
      photosensitivity. However, cholesta-5,7,9(11)-trien-3beta-ol (9-DDHC), a
      metabolite of 7-DHC, has been detected in plasma from SLOS patients. Because 9
      DDHC has strong absorption in the UVA range (approximately 15,000 @ 324 nm), we
      have examined its photobiology to determine whether it could be involved in SLOS
      photosensitivity. High levels of 7-DHC (0.65 mg/100 g wet weight) and measurable
      amounts of 9-DDHC (0.042 mg/100 g wet weight) were found in skin lipids extracted
      from CD-1 mice treated with AY9944 (trans-1,4-bis(2
      chlorobenzylaminomethyl)cyclohexane dihydrochloride), an inhibitor of 7-DHC
      reductase. Human HaCaT keratinocytes treated with 9-DDHC (10 microM) and then
      immediately exposed to UVA (15 J/cm2) exhibited an 88% decrease in viability
      (compared to dark controls). No damage was observed in cells exposed to 7-DHC/UVA
      or UVA alone. However, HaCaT keratinocytes treated with 7-DHC (5 microM) for 15 h
      and then exposed to UVA (30 J/cm2) were damaged. 9-DDHC was detected in
      keratinocytes incubated with 7-DHC. Reactive oxygen species were detected in 9
      DDHC/UVA-exposed cells using the fluorescent probe 5-(and 6-)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate acetyl ester. Singlet oxygen was generated
      when 9-DDHC was UVA irradiated in CCl4. UVA irradiation of 9-DDHC in acetonitrile
      generated superoxide and carbon-centered and alkoxyl radicals which were trapped
      by 5,5-dimethyl-1-pyrroline N-oxide. These findings suggest that reactive oxygen
      species generated by 9-DDHC may play a role in the UVA skin photosensitivity of
      SLOS patients. Furthermore, several statin drugs inhibit 7-DHC reductase, in
      addition to hydroxymethylglutaryl-CoenzymeA reductase, so that 9-DDHC may also be
      responsible for statin-derived photosensitivity, dermatoses, and cataract
      formation. Finally, we have previously detected 9-DDHC in skin lipids from normal
      subjects, so this sterol may also be the skin chromophore responsible for skin
      photoaging and UV-induced skin cancer.

PMID- 16814116
TI  - Whither conventional blood pressure measurement?

PMID- 16814119
TI  - Markers of inflammation are inversely related to physical activity and fitness in
      sedentary men with treated hypertension.
AB  - BACKGROUND: Physical inactivity is an important risk factor for atherosclerotic
      disease. We studied the relationship between physical activity and physical
      fitness and soluble markers of atherosclerotic activity in men with drug-treated
      hypertension. METHODS: The participants (n = 177, 40 to 74 years of age), who
      were randomly recruited from the Hypertension High Risk Management Trial (HYRIM),
      were overweight and had sedentary lifestyles. The inflammatory markers high
      sensitivity C-reactive protein (hs-CRP), soluble vascular cell adhesion molecule
      1 (sVCAM-1), soluble intercellular adhesion molecule-1 (SICAM-1) and soluble E
      selectin (sE-selectin) and the hemostatic markers soluble thrombomodulin (sTM),
      von Willebrand factor (vWf), and tissue plasminogen activator antigen (tPAag)
      were measured. Physical activity was measured by use of a questionnaire. Time to
      exhaustion in a bicycle test was used as an expression of physical fitness.
      RESULTS: The hs-CRP showed a significant inverse relationship with physical
      fitness independent of major cardiovascular risk factors (P = .017) but was not
      related to physical activity. The sE-selectin was significantly related to
      physical activity, although only when other factors were taken into account (P =
      .033), and it had no significant association with physical fitness. In addition
      there were strong associations between hs-CRP and sICAM-1 and the Framingham
      Coronary Heart Disease risk score (P < .001). CONCLUSIONS: The observed inverse
      relations between physical fitness and hs-CRP and between level of physical
      activity and sE-selectin in drug-treated, hypertensive sedentary men indicates a
      beneficial effect of good fitness status as well as activity of low intensity on
      vessel wall inflammation.

PMID- 16814117
TI  - Pressure wave reflections, central blood pressure, and aortic stiffness in
      patients with Adamantiades-Behcet's disease: a cross-sectional case-control study
      underlining the role of chronic corticosteroid treatment.
AB  - BACKGROUND: Adamantiades-Behcet's disease (ABD) is a multisystemic
      inflammatory/autoimmune disease involving both microcirculation and
      macrocirculation. Aortic stiffness index and aortic augmentation index (AI) are
      indices for the estimation of arterial stiffness and pressure wave reflections,
      respectively. The effect of anti-inflammatory and immunosuppressive drugs used in
      ABD on these indices is unknown. METHODS: In this cross-sectional study we
      examined 74 subjects with ABD (aged 40.1 +/- 12.5 years, 24 men) and 24 control
      subjects by using the noninvasive technique of radial artery applanation
      tonometry and pulse wave analysis for assessment of aortic AI by application of
      transfer functions. Echocardiography was used for assessment of aortic stiffness
      index. Classic cardiovascular (CV) risk factors, left ventricular and endothelial
      function of the brachial artery, as well as intima-media thickness of carotid
      artery, were also assessed. RESULTS: Corticosteroids were the only drug having a
      negative and independent effect on aortic AI, but not on aortic stiffness.
      Patients taking corticosteroids had lower aortic AI and central systolic blood
      pressure (BP), but not aortic stiffness and peripheral systolic BP, when compared
      to those without corticosteroids (21+/-14% v 12+/-14%, P < .050). Medication,
      traditional CV risk factors, and functional or structural CV parameters were all
      comparable among the two groups. The AI was similar between the control group and
      patients with ABD taking corticosteroids. CONCLUSIONS: The AI, but not aortic
      stiffness, is lower in patients with ABD taking corticosteroids compared to
      patients not taking corticosteroids and similar to the control group. These
      results imply a role of inflammation or immunomodulatory mechanisms in the
      regulation of pressure wave reflections.

PMID- 16814121
TI  - Altered expression of BK channel beta1 subunit in vascular tissues from
      spontaneously hypertensive rats.
AB  - Correlation of blood pressure (BP) with expression levels of large-conductance,
      voltage- and Ca2+-activated K+ (BK) channel beta1 subunit in vascular tissues
      from spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and Sprague
      Dawley rats (SD) at different ages was investigated. Systolic BP and BK beta1
      expression in mesenteric arteries at either mRNA or protein levels were not
      different among 4-week-old SHR, WKY, and SD. With hypertension developed at 7
      weeks and reached plateau at 12 weeks, expression levels of BK beta1 mRNA in
      mesenteric arteries and aortae from SHR during this period of time were
      significantly higher than in age-matched normotensive WKY. The BK beta1 protein
      expression was significantly higher in mesenteric arteries from 12-week-old but
      not 7-week-old SHR when compared with age-matched WKY and SD. The BK beta1
      protein levels in aortae were not different among 7-week-old SHR, WKY, and SD but
      were significantly lower in 12-week-old WKY than in age-matched SHR and SD.
      Captopril treatment normalized BP of 12-week-old SHR. This treatment
      downregulated BK beta1 protein in mesenteric arteries but upregulated it in
      aortae. No significant difference in BK alpha subunit expression was detected in
      mesenteric arteries from three strains of rats as well as the captopril-treated
      SHR. It appears that expression patterns of BK beta1 in vascular tissues vary
      depending on tissue types, animal age, and animal strains. Expression of BK beta1
      in mesenteric arteries is closely correlated with BP in SHR. Increased BK beta1
      expression in mesenteric arteries may represent a compensatory reaction to limit
      the development of hypertension.

PMID- 16814122
TI  - Association between awareness, treatment, and control of hypertension, and
      quality of life among older adults in Spain.
AB  - BACKGROUND: This study examines the relationship between awareness, treatment and
      control of hypertension, and health-related quality of life (HRQL) among older
      adults in Spain. METHODS: We conducted a cross-sectional study that included 3368
      subjects representative of the Spanish population > or = 60 years of age. We
      assessed HRQL using the MOS 36-Item Short Form (SF-36) questionnaire, and blood
      pressure (BP) was measured under standardized conditions. Data were analyzed
      using linear regression, adjusted for HRQL predictors (age, educational level,
      tobacco use, alcohol consumption, body mass index, physical activity, number of
      chronic diseases, and social support). RESULTS: Neither hypertension nor
      antihypertensive drug treatment or control were associated with worse HRQL. These
      results were also observed for awareness of hypertension among men, but in women
      awareness of hypertension was associated with a statistically significant (P <
      .01) and clinically relevant reduction (a 4- to 7-point lower score) in all HRQL
      dimensions. This association remained in evidence on many SF-36 scales, even
      after additional adjustment for medical advice to lose weight, reduce salt
      intake, increase physical activity, and moderate alcohol consumption. After
      further adjustment for prescription of antihypertensive drugs, however, the
      association between hypertension awareness and HRQL lost statistical
      significance, declining by >30% on most SF-36 scales. CONCLUSIONS: Neither
      hypertension nor antihypertensive drug treatment or control appears to lower HRQL
      in the elderly Spanish population. Yet, among women, awareness of hypertension is
      associated with lower HRQL, irrespective of change of lifestyle recommended by
      the physician. The impact of hypertension labeling on HRQL might be attributable
      in part to prescription of antihypertensive drugs.

PMID- 16814123
TI  - Is high job strain associated with hypertension genesis?
AB  - BACKGROUND: The aim of this analysis was to test, in a large sample of
      normotensive subjects, the short-term influence of job strain on the onset of
      hypertension. METHODS: According to the questionnaire of Karasek et al, job
      strain was divided into four modalities: (high strain, low strain, passive, and
      active) based on job demand (eg, the need to work hard and quickly) and job
      latitude (eg, control over skill use, time allocation, and organizational
      decisions) scores. High strain (HS) was defined by a high demand and a low job
      decision latitude. Individual data obtained in 926 (age 41 +/- 6 years) healthy
      normotensive or newly diagnosed hypertensive subjects were analyzed. Subjects
      participated in two prospective work site surveys designed to assess the
      influence of job strain on hypertension development. Relationships between job
      strain modalities and work site blood pressure (BP) levels were assessed using a
      general linear model. A complementary analysis using the the Pearson Phi
      coefficient (Z analysis) was implemented to explore nonlinear or scattered
      relationships between job strain and onset of hypertension. RESULTS: Systolic BP
      (SBP) was linearly related significantly to BMI and alcohol consumption, whereas
      diastolic BP (DBP) was related to age. The linear model did not find any
      relationship between SBP or DBP and job strain modalities. Using the Z analysis,
      development of systolic hypertension (SBP >140 mm Hg) was significantly
      associated with high job strain (P < .001). CONCLUSIONS: Our results suggest that
      there is no global relationship between job strain and BP levels. However our
      methodology revealed a significant association between job strain and work site
      BP in a predominantly male subgroup of newly diagnosed hypertensive subjects
      exposed to high job strain.

PMID- 16814124
TI  - Sedentary lifestyle and antecedents of cardiovascular disease in young adults.
AB  - BACKGROUND: The aim of this study was to determine whether sedentary young
      individuals are characterized by reductions in determinants of vascular health
      and insulin sensitivity relative to their physically active, age-matched peers.
      METHODS: A total of 135 otherwise healthy young men (n = 68) and women (n = 67)
      <40 years of age (28 +/- 5 years) were studied in this investigation and
      stratified into three groups based on physical activity status: 1) sedentary (n =
      73); 2) physically active (n = 24); and 3) endurance-trained (n = 38). Arterial
      compliance and flow-mediated dilation were determined by diastolic pulse contour
      wave analysis and echocardiographic imaging of the brachial artery respectively.
      Insulin sensitivity was estimated from the homeostasis model for insulin
      resistance and the 13C-glucose breath test. RESULTS: Both conduit (16.4 +/- 0.5 v
      19.5 +/- 0.7 mL/mmHg x 10; P < .01) and resistant (8.5 +/- 0.3 v 10.7 +/- 0.5
      mL/mmHg x 100; P < .01) artery compliance were significantly lower in sedentary
      subjects than in physically active or endurance-trained subjects, whereas flow
      mediated dilation was not different between the groups. The HOMA(IR) was 2.5-fold
      higher in the sedentary group than in the endurance-trained group (P < .05).
      CONCLUSIONS: Sedentary individuals are characterized by reductions in both
      arterial compliance and insulin sensitivity relative to their endurance-trained
      peers, independent of changes in conventional risk factors for cardiovascular
      disease. These findings lend further support for the need for regular physical
      activity in the prevention of cardiovascular disease in individuals of all ages.

PMID- 16814125
TI  - Prehypertension and obesity in adolescents: a population study.
AB  - BACKGROUND: Current blood pressure (BP) classification is based on the recent
      recommendations of the Joint National Committee on Prevention, Detection,
      Evaluation and Treatment of High Blood Pressure (JNC-7) and the 2003 European
      Society of Hypertension-European Society of Cardiology Guidelines for the
      Management of Arterial Hypertension. The JNC-7 introduced a new concept,
      prehypertension, and recommended health-promoting lifestyle modifications for
      these individuals. Obesity is also recognized as a major risk factor for the
      development of hypertension. We aimed to determine the prevalence of hypertension
      and obesity in a large cohort of adolescents and to assess whether
      prehypertension and body mass index (BMI) increase with increasing age. METHODS:
      A cross-sectional population-based study was performed using data collected
      during 1996 to 2002 in an army recruitment examination of 560,588 Israeli
      individuals 16.5 to 19 years of age. The subjects were divided according to
      gender and stratified by increasing 6-month intervals into five groups.
      Prehypertension was defined as BP 120 to 139 / 80 to 89 mm Hg. Overweight was
      defined as BMI 25 to < or = 30 and obesity as BMI >30 kg/m2. RESULTS: Mean
      systolic BP (SBP) and diastolic BP (DBP) were significantly higher in male
      subjects for all groups. By applying the JNC-7 criteria, 56.8% of male subjects
      and 35.8% of female subjects would be considered prehypertensive. There was a
      statistically significant increase in the mean SBP and DBP with age and BMI.
      Among male subjects 10.9% were overweight and 3.3% were obese; among female
      subjects, 11.1% were overweight and 3.2% were obese. The BMI did not increase
      with increasing age. The prevalence of prehypertension was significantly higher
      in obese subjects. CONCLUSIONS: Prehypertension is very common among Israeli
      adolescents. A substantial number of adolescents exhibit a BMI greater than
      normal. As both of these factors are known to be asssociated with increased
      cardiovascular risk, early institution of healthful lifestyle changes in a large
      proportion of this age group is recommended.

PMID- 16814126
TI  - How long shall the patient rest before clinic blood pressure measurement?
AB  - BACKGROUND: The optimal time at rest before clinic blood pressure (BP)
      measurement is still undefined. In this study in patients with essential
      hypertension, the time course of the hemodynamic changes during a 16-min rest in
      the chair-seated position was evaluated and compared with that observed in a
      stabilized postural condition, such as after a prolonged supine rest. METHODS: In
      55 untreated essential hypertensive patients, BP, heart rate, stroke volume
      (impedance cardiography), and systemic vascular resistances were measured every
      other minute during a 16-min rest in the chair-seated position and, in random
      sequence, in the last 16 min of a 60-min supine rest. RESULTS: Overall, systolic
      BP (SBP) and diastolic BP (DBP) decreased by 11.6 and 4.3 mm Hg, respectively,
      during the chair-seated rest; only a 1.8-mm Hg decrease in SBP was observed in
      the control supine study. The chair-seated fall in BP was associated with a
      decrease in systemic vascular resistances, in the absence of significant changes
      in cardiac index. From the logarithmic curve of SBP and DBP decrements, a half
      time of 5.8 and 5.5 min respectively, was calculated. Decrements in SBP, but not
      DBP, were inversely related to the corresponding baseline values. CONCLUSIONS: In
      untreated essential hypertensive patients a significant decrease in SBP and DBP
      associated with a systemic vasodilation was observed during a 16-min rest in the
      chair-seated position. Because approximately 75% of the spontaneous fall in BP
      occurred within 10 min, it appears that this time at rest before clinic BP
      evaluation could improve the precision and accuracy of the measurement.

PMID- 16814127
TI  - Regulation of angiogenic factors in angiotensin II infusion model in association
      with tubulointerstitial injuries.
AB  - BACKGROUND: Among various angiogenic factors, vascular endothelial growth factor
      (VEGF), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) play crucial roles in
      regulating angiogenesis and vascular integrity. Infusion of angiotensin-II (ang
      II) induces hypertension and focal renal tubulointerstitial injuries. In the
      present study we investigated the renal expression of VEGF, Ang1, Ang2, and
      corresponding receptors in association with tubulointerstitial lesions in a rat
      ang II infusion model. METHODS: Male Sprague-Dawley (SD) rats received an
      infusion of ang II or norepinephrine (NE) through osmotic minipumps for 14 days.
      Angiotensin II type 1 (AT1) or type 2 (AT2) receptor antagonist (losartan or
      PD123319, respectively) or hydralazine was co-administered. RESULTS: Interstitial
      fibrosis, infiltration of monocyte/macrophage, and peritubular capillary
      rarefaction induced by ang II was significantly attenuated in the losartan- or
      PD123319-treated groups. Immunoreactivity of VEGF and Ang1 in cortical tubules
      was increased by ang II and was attenuated by losartan or PD123319. The increase
      of VEGF induced by ang II was suppressed by losartan, and the increase of Ang1
      induced by ang II was inhibited by PD123319 as detected by immunoblot. The
      increase of flk-1 and flt-1 (VEGF receptors) and tie-2 (Ang1 receptor) induced by
      ang II was significantly suppressed by PD123319. These alterations were not
      observed in hydralazine plus ang II or NE-infused animals. CONCLUSIONS: These
      results demonstrate that an infusion of ang II induced the expression of VEGF
      mainly through AT1 receptors, and increased the expression of VEGF receptors, tie
      2, and Ang1/Ang2 ratio mainly through AT2 receptors. The increase of VEGF/flk
      1/flt-1 may be associated with vascular permeability, monocyte/macrophage
      infiltration, and rarefaction of peritubular capillaries, and the increase of the
      Ang1/Ang2 ratio may be a compensatory mechanism counteracting the permeability
      inducing effect of VEGF after ang II infusion.

PMID- 16814128
TI  - Microalbuminuria and cardiovascular risk assessment in primary hypertension:
      should threshold levels be revised?
AB  - BACKGROUND: Urinary albumin excretion and left ventricular mass are related to
      each other and to the risk of cardiovascular events in patients with primary
      hypertension. We aimed to identify a lower threshold for albuminuria that might
      improve detection of patients with left ventricular hypertrophy (LVH) and cost
      effectiveness in cardiovascular risk assessment. METHODS: Albuminuria and left
      ventricular mass index were assessed in 448 untreated, nondiabetic patients with
      primary hypertension. The impact that lower albuminuria cut-off levels might have
      on detecting LVH was evaluated with regard to test cost and sensitivity. This was
      done by a diagnostic algorithm consisting of albuminuria evaluation followed by
      echocardiography in the presence of normoalbuminuria. RESULTS: The area under the
      ROC curve of albuminuria in predicting LVH was 0.73. Using a lower albumin to
      creatinine ratio threshold than what is recommended by the guidelines (ie, 11.5
      mg/g), the sensitivity and specificity of albuminuria in identifying patients
      with LVH was 39% and 92%, respectively, which translated to positive and negative
      predictive values of 76% and 69%, respectively. When considering only patients
      without electrocardiographically detected LVH, routine screening for albuminuria,
      followed by echocardiography in the presence of albuminuria <or = 11.5 mg/g,
      allowed us to decrease the number of echocardiograms by 23%. CONCLUSION: Adopting
      a lower threshold to define microalbuminuria could prove to be cost-effective for
      assessing cardiovascular risk in hypertensive patients.

PMID- 16814130
TI  - Effect of education on blood pressure control in elderly persons: a randomized
      controlled trial.
AB  - BACKGROUND: It is not clear which educational strategy is most effective in
      helping patients to change their lifestyles. This study compared the efficacy of
      two different educational models on reducing blood pressure (BP). METHODS: This
      was a randomized controlled trial in ambulatory hypertensive patients >65 years
      of age. Workshops that aimed to develop self-management and patient empowerment
      (PEM) were compared to workshops that used a compliance-based model (CEM). The
      primary outcome was change in systolic BP at 3 months compared with basal values
      between groups (net reduction), measured by 24-h ambulatory BP monitoring.
      RESULTS: A total of 30 patients were educated with PEM and 30 others with CM.
      Both groups were statistically similar with regard to age (67 v 70 years),
      systolic BP (157 v 156 mm Hg) and diastolic BP (88 v 88 mm Hg), diabetes (23% v
      31%), and basal natriuresis 116 v 121 mEq/day). There were more women in the PEM
      group (57% v 30%). The PEM group showed a significant reduction of 8 mm Hg (95%
      confidence interval [CI] 2 to 15), whereas the CM group showed a reduction of 3
      mm Hg (95% CI -3 to 8), with a net reduction of 6 (95% CI -3 to 14). Mean net
      night-time systolic BP reduction was 12 mm Hg (95% CI 2 to 22). BP control was
      70% in PEM group vs 45% in CM group (P = 0.045). The relative odds ratio for BP
      control for the PEM group after adjustment for age, sex, diabetes, basal blood
      pressure and changes in pharmacological treatment was 3.7 (95% CI 1.05 to 13.1).
      CONCLUSION: Based on these study results, the self-management education model was
      significantly more effective than the compliance-based model in BP control.

PMID- 16814131
TI  - Different effects of transdermal and oral hormone replacement therapy on the
      renin-angiotensin system, plasma bradykinin level, and blood pressure of
      normotensive postmenopausal women.
AB  - BACKGROUND: This study compared the efficacy of transdermally administered
      estradiol with that of orally administered conjugated equine estrogens (CEE) on
      the renin-angiotensin system, plasma bradykinin level, and blood pressure (BP) in
      normotensive postmenopausal women (PMW). METHODS: A total of 38 normotensive PMW
      were randomly assigned to two groups. The transdermal hormone replacement therapy
      (HRT) group consisted of 19 women treated with a continuous transdermal estradiol
      patch (36 microg/day) plus cyclic oral medroxyprogesterone acetate (MPA; 2.5
      mg/day for 12 days) for 12 months. The oral HRT group consisted of 19 women who
      received continuous oral CEE (0.625 mg/day) plus cyclic oral MPA (2.5 mg/day for
      12 days) for 12 months. Plasma renin activity (PRA), serum angiotensin-converting
      enzyme (ACE) activity, plasma angiotensin (Ang) I, Ang II, and bradykinin
      concentrations, and BP were measured before and 12 months after the start of HRT.
      RESULTS: Transdermal HRT significantly decreased both diastolic and mean BP and
      concomitantly reduced bradykinin levels (all P < .05). However, no significant
      changes in PRA, ACE activity, Ang I, or Ang II levels were observed. The BP
      remained unchanged in the oral HRT group, but the PRA, Ang I, Ang II, and
      bradykinin levels had significantly increased and ACE activity had significantly
      decreased (all P < .05) at 12 months after the start of HRT. CONCLUSIONS:
      Transdermal HRT decreased BP in normotensive PMW without influencing Ang II,
      whereas oral HRT increased Ang II without altering BP. Transdermal HRT may be
      more beneficial than oral HRT with regard to BP and Ang II levels.

PMID- 16814132
TI  - Efficacy of add-on aldosterone receptor blocker in uncontrolled hypertension.
AB  - BACKGROUND: Uncontrolled hypertension (UH) may be caused by hyperaldosteronism,
      and some experts recommend the routine use of aldosterone antagonists in this
      condition. The purpose of this study was to evaluate the efficacy of this
      approach and to characterize those who respond effectively to an add-on
      aldosterone antagonist. METHODS: We retrospectively analyzed the effectiveness of
      spironolactone, an aldosterone antagonist, used as add-on therapy, compared with
      a standard add-on treatment, in patients referred to a hypertension clinic with
      UH despite the use of two or more antihypertensive drugs. RESULTS: A total of 340
      patients (186 male) with an average age of 63 +/- 14 years were followed for at
      least 3 months. Of the patients, 42 received add-on spironolactone and 298
      received an additional antihypertensive drug other than spironolactone. Baseline
      characteristics were similar in both groups. Blood pressure (BP) decreased
      significantly in both groups. In patients who received spironolactone, BP
      decreased by 23.2/12.5 mm Hg from 165 +/- 27/94 +/- 15 to 142 +/- 25/81 +/- 9 mm
      Hg, whereas in patients who received other add-on therapy BP decreased by 7.6/5.8
      mm Hg from 160 +/- 24/91 +/- 12 to 152 +/- 20/85 +/- 11 mm Hg (P < .05). Patients
      who received spironolactone had lower serum potassium levels than those who did
      not receive spironolactone 3.8 +/- 0.4 v 4.5 +/- 0.5 mmol/L respectively (P <
      .001). Potassium levels <4 mmol/L were associated with a greater reduction in BP.
      CONCLUSIONS: Add-on spironolactone is a highly effective add-on treatment in UH,
      mainly in patients with low serum potassium levels. Further studies assessing
      serum potassium as a marker for treatment approach are needed to establish the
      role of aldosterone antagonists in the management of UH.

PMID- 16814133
TI  - Duplex ultrasound and renin ratio predict treatment failure after
      revascularization for renal artery stenosis.
AB  - BACKGROUND: The aim of this study was to find predictors to identify patients
      with hypertension who will not improve after removal of renal artery stenosis
      (RAS). METHODS: Prospective study of patients with unilateral stenosis (>60%
      diameter reduction) and hypertension in 24-h measurements despite
      antihypertensive drugs, who underwent revascularization (surgery/angioplasty).
      Examinations were performed before treatment and after 3 and 6 months after
      exclusion of restenosis. Studies included 24-h blood pressure, creatinine
      clearance, 99Tc MAG3 scintigraphy, and measurements of renal vein plasma renin
      activity (PRA). Intrarenal resistance indices (RI) were determined with duplex
      ultrasound before and 30 min after administration of intravenous enalaprilat.
      Improvement of hypertension was defined by a score consisting of 24-h mean
      arterial pressure and the number of antihypertensive drugs. RESULTS: From
      December 2000 to December 2003, 50 patients completed the study. Improvement of
      hypertension was observed in 18 patients (36%). Comparison between responders (n
      = 18) and nonresponders (n = 32) revealed significant differences only for RI and
      PRA measurements. The largest area under the curve in receiver-operating
      characteristic (ROC) analysis for prediction of no improvement of hypertension
      was found for RI (stenosis side), which was nearly identical for measurements
      before and after administration of angiotensin-converting enzyme (ACE) inhibitor.
      The highest sensitivities and specificities predicting which patients will not
      improve were found for RIs > or = 0.55. The highest univariate odds ratio (OR 44,
      confidence interval [CI] 4.8-404) was found for the parameters of RI > or = 0.55
      and a renin ratio of <1:1.5. CONCLUSIONS: Resistance indices of the poststenotic
      kidney above 0.55 and a negative renin ratio can predict a poor outcome
      concerning arterial blood pressure response after restoration of renal blood flow
      for unilateral renal artery stenosis.

PMID- 16814134
TI  - Ghrelin inhibits vascular superoxide production in spontaneously hypertensive
      rats.
AB  - BACKGROUND: Ghrelin is a novel peptide involved in the control of appetite, but
      its role in vascular pathologies remains to be elucidated. Ghrelin was shown to
      decrease blood pressure (BP) and improve endothelial function. Its plasma levels
      are correlated with BP in humans. Mechanisms of these effects are unknown.
      Because oxidative stress and increased superoxide production by NAD(P)H oxidases
      (Nox) are critical in the pathogenesis of hypertension, we aimed to study the
      effects of ghrelin on vascular superoxide production and NAD(P)H oxidase activity
      in spontaneously hypertensive rats (SHR). METHODS: Aortic superoxide production
      and NAD(P)H oxidase activity were measured using lucigenin (5 micromol/L)
      chemiluminescence. Aortas from Wistar-Kyoto rats (WKY) were used as control.
      Direct superoxide scavenging properties of ghrelin were tested using xanthine
      xanthine oxidase system. RESULTS: Both basal superoxide production and vascular
      NADPH oxidase activity were significantly higher in aortas from SHR, than from
      WKY. Preincubation of aortic segments from SHR or WKY with ghrelin caused
      concentration-dependent (from 50 pg/mL to 5 ng/mL) decrease of basal superoxide
      production. Vascular NAD(P)H oxidase activity was inhibited by ghrelin,
      abolishing the difference between SHR and basal WKY. Ghrelin did not affect
      superoxide release from the in vitro xanthine-xanthine oxidase system, indicating
      lack of direct superoxide scavenging properties or inhibitory effects on xanthine
      oxidase in vitro. Nitric oxide synthase (NOS) inhibition, using N(omega)-nitro-L
      arginine methyl ester (L-NAME), partially blunted the effects of ghrelin on NADPH
      oxidase activity indicating potential role of nitric oxide. CONCLUSIONS: Ghrelin
      inhibits vascular oxidative stress in SHR. This effect is likely related to the
      inhibition of vascular NAD(P)H oxidases.

PMID- 16814135
TI  - Interaction of grapefruit juice and calcium channel blockers.
AB  - Drug-drug interactions are commonly recognized occurrences in the hypertensive
      population. Drug-nutrient interactions, however, are less well appreciated. The
      grapefruit juice-calcium channel blocker interaction is one that has been known
      since 1989. The basis for this interaction has been diligently explored and
      appears to relate to both flavanoid and nonflavanoid components of grapefruit
      juice interfering with enterocyte CYP3A4 activity. In the process, presystemic
      clearance of susceptible drugs decreases and bioavailability increases. A number
      of calcium channel blockers are prone to this interaction, with the most
      prominent interaction occurring with felodipine. The calcium channel blocker and
      grapefruit juice interaction should be incorporated into the knowledge base of
      rational therapeutics for the prescribing physician.

PMID- 16814136
TI  - MRI-guided preoperative wire localization of nonpalpable breast lesions.
AB  - With the increasing use of magnetic resonance imaging (MRI), the physician is
      more frequently confronted with nonpalpable breast lesions that are only visible
      on MRI. In these cases, it is often difficult to obtain adequate material for
      pathological examination. One of the methods that may be performed is excisional
      biopsy after MRI-guided wire localization. This study intends to examine the
      feasibility and added benefit of this method. It appears to be a reliable and
      useful tool that is, therefore, of additional benefit to surgical practice.

PMID- 16814137
TI  - Ultrasonography-guided percutaneous microwave ablation of peripheral lung cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility and therapeutic
      effectiveness of ultrasonography (US)-guided percutaneous microwave ablation
      (PMA) in the treatment of peripheral lung cancer. METHODS: From December 2002 to
      September 2003, 12 Chinese patients with 16 histologically proven lung malignant
      tumors (6 primary and 10 metastatic) were treated with US-guided PMA. All tumors
      were located at the peripheral portions of the lung where the tumors were in
      direct contact with visceral pleura and visualized on US. A total of 21
      insertions with 25 applications was administered to the 16 tumors. There was no
      radiation or chemotherapy combined with PMA. RESULTS: Based on the follow-up
      period of 6-40 months (average=20 months), seven patients survived without
      serious complications and five patients died from metastasis after PMA. The size
      of treated tumors was decreased in all cases (10 tumors with moderate to
      remarkable area reduction and 6 tumors with mild area reduction). Blood flow in
      the tumors became either invisible or diminished on color Doppler flow imaging,
      which showed 9 tumors with no enhancement and 7 tumors with partially decreased
      enhancement on contrast-enhanced computed tomography after PMA. All patients
      experienced improvement of clinical symptoms after PMA treatment. CONCLUSIONS:
      Ultrasonography-guided PMA, a mildly invasive procedure, is an effective, safe,
      and feasible method for treating peripheral lung tumors. Percutaneous microwave
      ablation provides an alternative therapy for patients with inoperable peripheral
      lung cancer as well as for patients who refuse radiation or chemotherapy.

PMID- 16814138
TI  - Clinical follow-up of 50 patients treated by percutaneous lumbar discectomy.
AB  - A series of 50 patients presenting with lumbar discogenic disease, and treated by
      percutaneous discectomy using the Dekompressor system (Stryker, Kalamazoo, MI,
      USA), were followed for more than 6 months, by analyzing the evolution of the
      painful symptomatology with the visual analog scale (VAS) system. All patients
      had been under treatment with analgesic or anti-inflammatory agents. The
      intensity of the pain was measured 2, 7, 30, and 180 days after the percutaneous
      discectomy. An improvement in the painful symptomatology of less than 30%,
      observed in 11 cases and in 1 case of epidural pathology, was considered an
      unsuccessful result. A decrease of the pain of more than 70% was observed in 72%
      of cases, either with the end of the symptoms of pain as noted in 79.5% of
      patients or with a marked reduction of the medical treatments obtained in 21.5%.
      The results obtained were already almost definitive at the seventh day of follow
      up, and further controls rarely demonstrated an improvement in the pain. The
      location of the herniated disc is a parameter which appears to be very important
      in the efficacy of percutaneous discectomy. We noted an improvement of more than
      70% in 79% of the posterolateral foraminal or extraforaminal hernias, although
      these favorable results were observed only in 50% of the posteromedian hernias.

PMID- 16814139
TI  - Frequency and etiology of midesophageal diverticula at barium esophagography.
AB  - Midesophageal diverticula were identified at 8 of 218 (3.6%) esophagrams
      performed over a 3-year period in adult patients with no prior history of
      gastroesophageal surgery. All eight patients received a final diagnosis of
      esophageal dysmotility with secondary pulsion diverticula, and seven of eight
      (88%) patients had abnormal peristalsis noted during the esophagram. We conclude
      that most, if not all, midesophageal diverticula are pulsion in etiology, and the
      detection of a midesophageal diverticulum should prompt a careful search for
      underlying dysmotility.

PMID- 16814140
TI  - MR colonoscopy at 3.0 T: comparison with 1.5 T in vivo and a colon model.
AB  - PURPOSE: Retrospectively, magnetic resonance (MR) colonography images obtained
      from a colon model and in routine examinations of patients screened for polyps
      were compared in terms of whether, and to what degree, image quality improved at
      a higher field strength of 3.0 T compared to 1.5 T. MATERIALS AND METHODS: One
      hundred twenty-eight MR colonography images from 40 patients, of whom 20 had each
      been scanned at 1.5 and 3.0 T, respectively, using a four-element phased-array
      torso coil, were compared. At both field strengths, imaging included T1-weighted
      fat-suppressed spoiled gradient-echo (T1-fs-GE), T2/T1-weighted fast imaging
      employing steady-state acquisition (FIESTA), and T2-weighted single-shot fast
      spin-echo (T2-SSFSE), with breath-hold technique. Using receiver operating
      characteristic analysis performed by seven readers, the three types of images
      from the colon model and from 20 patients each at 1.5 and 3.0 T were compared.
      While a time window of 20 s was allowed for picture assessment in a chance
      generated succession of images on a monitor, image quality was rated with a score
      of 1-5 (1=very good; 5=very bad). Statistical significance was calculated with
      Mann-Whitney U test. RESULTS: At both field strengths, T2-SSFSE images received
      the best ratings, followed by FIESTA images (P=.001). Although, overall, the 3.0
      T images obtained scores worse than those of the 1.5-T images, a better detection
      of phantom polyps was noted in the colon model (P=.001). CONCLUSION: Although MR
      colonography with the breath-hold technique using the same four-element phased
      array coil at 3.0 and 1.5 T does not perform better at a higher field strength in
      general, an improved detection of small polyps may be obtained.

PMID- 16814141
TI  - Shoulder distension arthrography in adhesive capsulitis.
AB  - Capsular retraction of the shoulder often occurs as a solitary pathological
      process; half of the cases are of primitive nature. In the past 10 years or more,
      distension of the shoulder joint has proven to be an efficient percutaneous
      treatment, and various techniques have been proposed. We report on our technique,
      which was performed on a series of 200 patients, and on the results observed in
      27 patients with a precise evaluation of progressive changes in movements of the
      joint.

PMID- 16814142
TI  - Localizing hyperfunctioning parathyroid tissue: MRI or nuclear study or both?
AB  - The surgical approach to primary hyperparathyroidism patients has changed
      recently with minimally invasive surgery becoming more common. This retrospective
      study reviews the relative sensitivities of dual-phase sestamibi (DP-SI) and
      magnetic resonance imaging (MRI) in preoperative patients. We found that MRI was
      more sensitive, but the difference was not statistically significant. Magnetic
      resonance imaging enhanced the ability to localize abnormal tissues when the DP
      SI was negative. Together, both tests demonstrated a sensitivity of 92%. We
      recommend performing DP-SI initially, and if negative, MRI. This should provide
      the highest imaging sensitivity at the lowest cost.

PMID- 16814143
TI  - CT pulmonary angiography for the detection of pulmonary embolism: interobserver
      agreement between on-call radiology residents and specialists (CTPA interobserver
      agreement).
AB  - PURPOSE: The aim of this study was to prospectively determine interobserver
      agreement between on-call radiology residents and specialists in the
      interpretation of computed tomographic pulmonary angiography (CTPA). METHODS:
      CTPA examinations obtained between January 2002 and March 2003 were interpreted
      by a radiology resident on call and by two radiology specialists. Agreement was
      assessed using percentage of agreement between interpreters and by the kappa
      coefficient. Sensitivity of residents' interpretations was calculated by relating
      them to the interpretation of Specialist 1, which served as the gold standard.
      RESULTS: Of the 81 CTPA examinations evaluated, there was agreement of 93% and
      91% for the diagnosis of pulmonary embolism (PE) and of 97% and 85% for the
      exclusion of PE with Specialist 1 and 2, respectively. The concordance between
      residents' interpretations and those of Specialist 1 was very high (kappa=.8),
      and with those of Specialist 2 was high (kappa=.7). In all cases of agreement
      between the two specialists, there was complete agreement between the
      specialists' and the residents' intepretations. CONCLUSIONS: Our study showed
      good to very good agreement of residents' interpretations with each of the
      radiology specialists. Therefore, relying on the residents' preliminary
      interpretations during after-hour calls is reasonable.

PMID- 16814144
TI  - Multicentric granulocytic sarcoma of the breast: mammographic, sonographic, and
      MR findings.
AB  - A rare case of granulocytic sarcoma (GS) of the bilateral breasts after complete
      remission of acute myelogenous leukemia is reported. Mammogram showed multiple
      irregular high-density masses, and sonogram demonstrated multiple irregular low
      echoic masses with a posterior shadow in the bilateral mammary glands. Contrast
      enhanced MR images showed multiple irregular enhancing masses. None of those
      findings were pathognomonic of GS. However, MR image was useful to evaluate the
      response of the chemotherapy and detect the nonpalpable relapse tumor and
      determine the introduction of the radiation therapy early.

PMID- 16814145
TI  - Noninvasive evaluation of a fistula between a giant coronary aneurysm and
      coronary sinus performed via multidetector row computed tomography.
AB  - Coronary artery fistula (CAF) is an uncommon anomaly of congenital and rarely
      iatrogenic etiology. Most of the patients are asymptomatic, and the anomaly is
      incidentally recognized during a coronary angiography performed for other
      reasons. Also, coronary artery aneurysms are rare. We report a case of CAF
      associated with a giant aneurysm evaluated using multidetector row computed
      tomography.

PMID- 16814147
TI  - Percutaneous jejunostomy and stent placement for treatment of malignant Roux-en-Y
      obstruction: a case report.
AB  - Nineteen months after a Whipple procedure for pancreatic carcinoma, a 79-year-old
      woman developed recurrent tumoral strictures of the bile ducts and afferent Roux
      en-Y limb with resultant jaundice, cholangitis, and liver abscess. Transhepatic
      abscess and biliary drainages were performed first. Afferent loop obstruction was
      too far from biliary anastomosis to be crossed via the transhepatic route.
      Percutaneous jejunostomy and stenting were performed to relieve the malignant
      afferent loop syndrome. After initial relief of symptoms, jaundice recurred in
      relation to peritoneal carcinomatosis progression and was treated with
      percutaneous jejunostomy drainage until patient's death. Therapeutic options of
      tumoral occlusion of afferent loops are reviewed.

PMID- 16814146
TI  - Gastrointestinal carcinoid tumors in rare locations: imaging findings.
AB  - In this article, we present radiological findings in three patients with
      mesenteric, gastric, and rectal carcinoid tumors. More than 90% of the carcinoid
      tumors arise in the gastrointestinal system (GIS). They comprise 2% of all GIS
      tumors and are usually located in the small intestine and the appendix. On the
      other hand, gastric, rectal, and mesenteric carcinoids are rare. Better knowledge
      of radiological features of carcinoid tumors in rare locations will prevent
      diagnostic delays and development of carcinoid syndrome.

PMID- 16814148
TI  - Unsuspected retained 60-cm intravenous guidewire.
AB  - We report a case of a retained 60-cm intravenous guidewire that had inadvertently
      slipped into a patient during preoperative central line placement. This
      unsuspected guidewire was unrecognized on postoperative chest and abdominal
      radiographs, but was subsequently diagnosed much later at computed tomography.
      After 150 days within the patient, the guidewire was retrieved percutaneously
      without complication.

PMID- 16814149
TI  - Regarding "phenylpropanolamine and hemorrhagic stroke in the hemorrhagic stroke
      project".

PMID- 16814150
TI  - Regarding "Phenylpropanolamine and hemorrhagic stroke in the hemorrhagic stroke
      project": mercenary epidemiology--data reanalysis and reinterpretation for
      sponsors with financial interest in the outcome.

PMID- 16814153
TI  - Intensity-modulated radiation therapy for gynecologic cancers: pitfalls, hazards,
      and cautions to be considered.
AB  - Intensity Modulated Radiation Therapy (IMRT) is considered a major advance in
      radiaton therapy (RT) capability. Therefore, it has been rapidly accepted and
      implemented in the treatment of multiple cancers in which RT plays a major role.
      Early reports of IMRT in gynecologic cancers have been largely favorable,
      particularly in terms of decreased acute morbidity. However, IMRT has not been
      prospectively shown to be superior to conventional 3-dimensional RT techniques
      when judged against criteria established in advance. Furthermore, there are many
      reasons to consider the possibility that outcomes might be compromised by IMRT
      techniques used to treat gynecologic cancers. This article reviews the potential
      pitfalls and hazards of IMRT techniques on patient safety and treatment efficacy.
      In addition, the article describes multiple technical issues with IMRT
      implementation, arguing for caution in IMRT use.

PMID- 16814154
TI  - Potential advantages of intensity-modulated radiation therapy in gynecologic
      malignancies.
AB  - Radiation therapy (RT) plays a critical role in the management of gynecologic
      malignancies. Conventional RT may treat a large amount of normal tissue, which
      results in increased toxicities and a limitation on total dose. Intensity
      modulated radiation therapy (IMRT) helps reduce the dose to normal tissue while
      delivering a higher dose to the tissues with microscopic or gross disease. This
      may have a potential benefit in the treatment of gynecologic malignancies
      especially in difficult cases such as grossly positive nodes, recurrent disease,
      and vulvar cancer. However, there is very little clinical data and very little
      experience with the use of IMRT in gynecologic malignancies. Therefore, before
      complete acceptance of IMRT in the treatment of gynecologic malignancies, large
      multicenter trials are needed to help develop guidelines and standards.

PMID- 16814155
TI  - The role of radiation therapy in locally advanced endometrial cancer.
AB  - Locally advanced endometrial cancer comprises those patients considered at high
      risk for recurrence of disease and death from cancer, which include patients with
      pathologic stage III and IV endometrioid adenocarcinoma and patients with uterine
      papillary serous carcinoma regardless of stage. The management of locally
      advanced endometrial cancer patients remains an evolving issue. The primary
      treatment for these patients is surgical resection. Controversy exists over the
      optimal adjuvant treatment, particularly in patients whose disease is completely
      resected. This article addresses the role of adjuvant radiation therapy for these
      locally advanced high-risk endometrial cancer patients. In addition, this article
      reviews the current data and treatment approaches using radiation therapy in the
      management of these high-risk patients.

PMID- 16814156
TI  - When and how should adjuvant radiation be used in early endometrial cancer?
AB  - The role of adjuvant radiation therapy (RT) in early endometrial cancer is no
      longer clearly defined. The increased use of surgical lymph nodes staging and the
      perceived "lack of survival advantage" with adjuvant pelvic RT leads to a wide
      array of conclusions on who should be treated and if so how. The purpose of this
      review is 2-fold: first, to determine the scientific validity of some of the
      conclusions drawn about the lack of survival impact of adjuvant pelvic RT and,
      second, to determine which treatment option provides the best therapeutic ratio.
      Overall survival may not be the ideal endpoint for early-stage endometrial cancer
      where death more often than not is because of causes other than endometrial
      cancer. Observation after hysterectomy may have the best morbidity profile, yet
      it may not be the option with the best therapeutic ratio. Finding a suitable
      alternative such as intravaginal RT or using intensity-modulated radiation
      therapy may ultimately prove to be the option with the best therapeutic ratio.
      The data learned from surgical lymph nodes staging and from the 2 recent
      randomized trials on the role of pelvic RT in early endometrial cancer need not
      be ignored nor held as the final answer. Perhaps, rectal cancer should be used as
      an example of how an incremental use of individual adjuvant therapies, each
      impacting outcome little at a time, ended up improving overall survival. If we
      were to use the current prevailing approach in endometrial cancer for rectal
      cancer, patients would still be treated with surgery alone.

PMID- 16814158
TI  - Integrating radiation into the management of vulvar cancer.
AB  - Vulvar cancer is a challenge to treat given the rarity of this disease and the
      variety of clinical presentations. The traditional approach to treatment has been
      with primary surgery. Radiation, often with concurrent chemotherapy, is now
      becoming an integral part of disease management through attempts to minimize
      surgical morbidity and improve treatment outcomes. This article highlights the
      advances made in understanding the role radiation and chemotherapy have to play
      in the adjuvant and definitive management of vulvar cancer.

PMID- 16814157
TI  - Controversies and new developments in gynecologic brachytherapy: image-based
      intracavitary brachytherapy for cervical carcinoma.
AB  - The current clinical practice for cervical cancer intracavitary brachytherapy in
      most centers is to prescribe the dose to point A. However, this is an empirical
      point and does not necessarily reflect dose to the tumor. Although 3-dimensional
      image-based treatment planning is extensively used in prostate brachytherapy,
      only a few institutions have used it to shape the dose distribution in cervical
      brachytherapy. To facilitate and standardize image-based dosimetry for cervical
      cancer brachytherapy, the American Image-guided Brachytherapy Working Group and
      the European Gynecological GEC-ESTRO Working Group have recently proposed
      nomenclature for volume definition and recommendations for image-based
      intracavitary brachytherapy for cervical cancer. The recommendations of the 2
      groups are very similar and are discussed together in this article. Proposals are
      made for research in image-based brachytherapy for cervical cancer. At a recent
      transatlantic image-based cervical cancer brachytherapy workshop (Chicago, IL,
      July 28, 2005), it was suggested that because the recommendations are so similar
      and to prevent confusion, the nomenclature suggested by the European Group be
      adopted and future joint contouring workshops be organized to facilitate image
      based cervical cancer brachytherapy.

PMID- 16814159
TI  - Chemoradiotherapy in the treatment of cervical cancer.
AB  - The advantage of concurrent chemoradiotherapy over radiotherapy alone in patients
      with cervical cancer has now been well documented in a series of prospective
      randomized trials. Six of these trials compared a cisplatin-based regimen (either
      cisplatin alone administered weekly or a combination of cisplatin and 5
      fluorouracil) with radiotherapy alone or radiotherapy plus another, less
      effective chemotherapy; 5 of these 6 trials showed a benefit with concurrent
      chemotherapy. Individual trials have also suggested that epirubicin and the
      combination of mitomycin plus 5-fluorouracil are effective when administered
      concurrently with radiotherapy. Other drugs, particularly biologic response
      modifiers, are currently being studied for their potential benefit in combination
      with radiation and cisplatin. Although the side effects of chemoradiotherapy with
      weekly cisplatin or cisplatin plus 5-fluorouracil are tolerable for most
      patients, the addition of concurrent chemotherapy to radiotherapy markedly
      increases hematologic and gastrointestinal side effects and adds to the overall
      complexity of treatment. Successful management requires particularly close
      monitoring of hematologic parameters, fluid balance, electrolyte levels, dietary
      condition, and social support. Careful coordination between caregivers is
      crucial. Although early publication of some trials precluded mature analysis of
      late radiation effects, available data suggest that the addition of concurrent
      chemotherapy does not markedly increase the risk of major late complications.
      Most women with locoregionally advanced cervical cancers (stage IB2 or greater or
      positive pelvic lymph nodes) that are confined to the pelvis are candidates for
      chemoradiotherapy. However, the benefit of adding concurrent chemotherapy to
      radiotherapy should always be weighed against the risk of serious acute side
      effects, particularly in patients who have serious coexisting medical conditions
      that would have precluded or discouraged enrollment in the prospective trials.

PMID- 16814160
TI  - Magnetic resonance imaging and positron-emission tomography imaging in the 21st
      century as tools for the evaluation and management of patients with invasive
      cervical carcinoma.
AB  - For over 4 decades, the delivery of definitive radiotherapy to patients with
      carcinoma of the cervix has involved both external beam and brachytherapy. Both
      of these therapeutic modalities have been traditionally linked to 2-dimensional
      radiographic guidance. Currently, the staging of these tumors still resides in
      clinical examinations and 2-dimensional diagnostic x-rays. Recently, there have
      been significant technological developments in imaging, namely magnetic resonance
      imaging and positron-emission tomography. These novel radiologic advances have
      subsequently led to a number of investigational studies, which in turn have shown
      a "paradigm shift" not only in the diagnosis but also in the radiation delivery
      used for patients with invasive carcinoma of the cervix.

PMID- 16814161
TI  - Intracytoplasmic sperm injection--an assisted reproduction technique that should
      make us cautious about imprinting deregulation.
AB  - OBJECTIVE: Due to the extensive use of intracytoplasmic sperm injection (ICSI) in
      assisted reproduction, not only among couples with severe male factor infertility
      problems, but to a broader scale, a lot of concern has been raised regarding the
      safety of the method and its implications in epigenetic control and imprinting
      dysregulation. This review means to provide a comprehensive report of the
      published scientific data, outline putative associations between ICSI and
      epigenetic control, and suggest measures to improve the current state of affairs
      and reach more scientifically consolidated results. METHODS: This review was
      conducted by studying a broad spectrum of articles dealing with the subject of
      epigenetic control and its relation with ICSI. We tried to view the two subjects
      as parallel procedures that occur in the organism and by delineating the
      molecular and biochemical steps that comprise them make suggestions about
      putative associations between ICSI and epigenetic control. CONCLUSIONS: No hard
      evidence presented at the moment can prove or disapprove ICSI's implications in
      epigenetic control. Nevertheless, we take the view that more comprehensive, long
      term, and properly designed studies are imperative to be applied on a large-scale
      basis. We urge cautiousness, since the welfare of our progeny is what is at
      stake.

PMID- 16814162
TI  - SHP protein tyrosine phosphatase expression in rat uterine tissue.
AB  - OBJECTIVE: Enhanced tyrosine phosphorylation of phospholipase C-gamma1
      (PLCgamma1) is associated with increased spontaneous contractile activity.
      PLCgamma1 phosphorylation is regulated by cellular protein tyrosine kinases and
      tyrosine phosphatases (PTPs). The studies in this report were undertaken to
      characterize the expression of two PTPs known to bind to PLCgamma1: Src-homology
      phosphatase type-1 (SHP-1) and type-2 (SHP-2). METHODS: Uterine and other tissues
      were obtained from non-pregnant (estrus) and pregnant (gestational day 12 through
      day 1 postpartum) Sprague-Dawley rats. PTP activity in myometrial homogenates was
      determined using an in vitro fluorometric PTP assay with and without bpV(phen) (a
      nonselective PTP inhibitor), or PTP-Inhibitor 1 (PTP-I1, a SHP selective
      inhibitor). Western blots were performed using polyclonal antibodies to SHP-1 and
      SHP-2. Immunoprecipitation studies were performed to demonstrate an association
      between PLCgamma1 and the SHP proteins. RESULTS: The in vitro PTP assays
      demonstrated comparable enzyme activity in myometrium from estrus and pregnant
      animals. BpV(phen) produced a 93% reduction in PTP activity (P <.05); similarly,
      PTP-I1 produced an 86% reduction in enzyme activity (P <.05). Western blots
      confirmed robust expression of both SHP-1 and SHP-2 protein in rat uterus. SHP-1
      expression decreased significantly at the end of gestation; in contrast, SHP-2
      levels remained stable. Immunoprecipitation studies confirmed an association
      between the SHP proteins and PLCgamma1. CONCLUSION: These studies have
      demonstrated that SHP-1 and SHP-2 are expressed in rat myometrium and appear to
      be responsible for the PTP activity in this tissue, thereby providing a molecular
      mechanism for the modulation of PLCgamma1 phosphotyrosine levels in the rat
      uterus.

PMID- 16814164
TI  - Multiplex measurement of cytokine/receptor gene polymorphisms and interaction
      between interleukin-10 (-1082) genotype and chorioamnionitis in extreme preterm
      delivery.
AB  - OBJECTIVES: To establish a multiplex amplification refractory mutation system
      (ARMS) in fluid and dried whole blood, and to perform a pilot study to examine
      the role for single-nucleotide polymorphisms (SNPs) of inflammation-associated
      genes (interleukin [IL]-1 and -10, tumor necrosis factor-alpha [TNFA], and toll
      like receptor-4 [TLR4]) and their interaction with clinical chorioamnionitis
      (CAM) in prematurity. METHODS: We established a quadruplex ARMS to detect the
      four above SNPs. Fifty-four women delivered at gestational age less than 32 weeks
      and 83 healthy female volunteers were genotyped. We compared (1) mothers of
      preterm infants with volunteers, and (2) women delivered before 29 weeks'
      gestation (n = 29) with those delivered at 29 to 31 completed weeks (n = 25).
      RESULTS: Multiplex ARMS is feasible using both fluid and dried whole blood. We
      found no overall differences in genotype and allele frequencies between mothers
      of preterm infants and volunteers. Among women who had a preterm delivery, those
      with both CAM and IL10(-1082)*G allele, the risk for delivery before 29 weeks was
      markedly increased (odds ratio [OR] 22, 95% confidence interval [CI] 2.5 - 191).
      CONCLUSION: The presence of both CAM and IL10(-1082)*G might play a role in
      extreme preterm delivery less than 29 weeks.

PMID- 16814163
TI  - Mechanisms of paracrine regulation by fetal membranes of human uterine
      quiescence.
AB  - OBJECTIVE: To test the hypothesis that fetal membranes (chorion or amnion)
      release one or more factors responsible for myometrial quiescence. METHODS:
      Myometrial samples were excised from women at elective term cesarean delivery
      prior to the onset of labor. Fetal membranes were obtained after cesarean
      delivery either before or during labor, and either term (greater than 37 weeks)
      or preterm (less than or equal to 36 weeks). Myometrial strips were placed in
      organ baths and contractions stimulated by oxytocin (10(-8) M). Contractility was
      measured under isometric conditions before and after exposure to fetal membranes
      or conditioned medium. The impact of either membrane or conditioned media on
      contractility was determined before and after myometrial K+ channel blockade.
      RESULTS: Both chorion and amnion and their respective conditioned mediums
      decrease oxytocin-stimulated myometrial contraction. The inhibitory effect was
      greatest with membranes from preterm pregnancies (mean gestation 32 weeks, P
      <.05). The inhibitory effect was detectable in the presence of term labor, but
      was absent when the fetal membranes were obtained after preterm labor.
      Iberiotoxin, an inhibitor of large conductance Ca2+-activated K+ channels
      (BK(Ca)) reduced the effect of fetal membranes by 50% (P <.05). CONCLUSION: We
      conclude that human fetal membranes release one or more factors that inhibit
      oxytocin-induced myometrial contractility. We suggest this factor (or factors)
      acts mainly by opening myometrial BK(Ca). The findings further support our
      hypothesis that the fetal membranes release a factor (or factors) that is central
      to myometrial quiescence and its premature loss leads to preterm delivery.

PMID- 16814165
TI  - Placental lactate transporter activity and expression in intrauterine growth
      restriction.
AB  - OBJECTIVES: To compare lactate uptake in the microvillous plasma membrane
      (maternal facing [MVM]) in term and preterm placentas in intrauterine growth
      restriction (IUGR) and appropriate weight for gestational age (AGA) controls, and
      in the basal plasma membrane (fetal facing [BM]) at term. In addition, we examine
      the expression of monocarboxylate transporters (MCT1 and MCT4). METHODS: We
      measured [14C] L-lactate uptakes into vesicles prepared from MVM and BM,
      stimulated by an inwardly directed H+ gradient. MCT expression was examined by
      Western blotting. RESULTS: In term placentas, mean (+/- SE) [14C] L-lactate
      uptake into MVM vesicles of the IUGR (n = 6) and AGA (n = 11) groups at initial
      rate was similar (15.4 +/- 2.3 versus 15.0 +/- 1.1 pmol/mg protein/20 s). In
      preterm placentas, in IUGR (n = 3) and AGA (n = 3) groups, [14C] l-lactate uptake
      into MVM was also not significantly different. In BM vesicles from term
      placentas, [14C] L-lactate uptake was significantly lower in IUGR (n = 5) than in
      AGA (n = 6) controls (3.6 +/- 0.4 versus 5.6 +/- 0.6 pmol/mg protein/20 s, P
      <.05). MCT1 and MCT4 were expressed in BM vesicles, but there was no difference
      in expression between the IUGR and AGA groups. CONCLUSIONS: These findings
      suggest that in IUGR placental lactate transport capacity in the BM is reduced,
      which may adversely affect placental lactate clearance.

PMID- 16814166
TI  - Decreased plasma visfatin concentrations in women with gestational diabetes
      mellitus.
AB  - OBJECTIVE: To test the hypothesis that plasma visfatin concentrations will be
      lower in women with gestational diabetes mellitus, we evaluated women with
      gestational diabetes mellitus and healthy pregnant women, and then correlated
      their plasma visfatin concentrations with body mass index (BMI) and various other
      parameters. METHODS: A total of 40 women were evaluated: 20 women with
      gestational diabetes mellitus and 20 healthy pregnant women to serve as control
      subjects. Plasma visfatin concentrations were analyzed using an enzyme-linked
      immunosorbent assay. RESULTS: Plasma visfatin concentrations were significantly
      lower in the gestational diabetes mellitus group (9.4 +/- 3.8 ng/mL) than in the
      healthy control group (12.6 +/- 4.5 ng/mL) (P = .023). A negative correlation was
      found between plasma visfatin concentrations and maternal age (r = -0.399, P =
      .011), first trimester body weight (r = -0.350, P = .027), and first trimester
      BMI (r = -0.336, P = .034). Multiple linear regression analysis revealed that
      maternal age (P = .017) and gestational diabetes mellitus/no gestational diabetes
      mellitus (P = .044) were independently related to plasma visfatin concentrations.
      However, no relationship was found with either gestational age at the time of
      sampling or first trimester BMI. CONCLUSIONS: Our results show that there are
      decreased concentrations of plasma visfatin in gestational diabetes mellitus
      subjects and this may indicate that visfatin plays a role in the pathogenesis of
      gestational diabetes mellitus. However, further experiments are needed to clarify
      this role.

PMID- 16814167
TI  - Investigation of free radical scavenging enzyme activities and lipid peroxidation
      in human placental tissues with miscarriage.
AB  - BACKGROUND: Miscarriage (early pregnancy failure) is a pregnancy-related disease,
      the pathophysiology of which is still not completely understood. Lipid
      peroxidation and alterations in antioxidant enzyme activities may be of
      importance in the pathogenesis of this disorder. This study was planned to
      investigate the possible relation between free radical scavenging enzyme
      activities and lipid peroxidation levels in placenta tissues with miscarriage.
      METHODS: Placental tissue samples were obtained from 21 patients who had
      miscarried and 25 normal pregnant women undergoing elective abortion as a control
      group. Total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and
      catalase (CAT) enzyme activities and levels of thiobarbituric acid reactive
      substances (TBARS), antioxidant potential (AOP), and nonenzymatic superoxide
      radical scavenger activity (NSSA) were measured in the placental tissues.
      RESULTS: GSH-Px, CAT activities, and TBARS levels were found to be significantly
      increased, while T-SOD and NSSA values decreased in patients with early pregnancy
      failure when compared with women undergoing elective abortion (control group).
      However, there were no significant differences in AOP levels between the groups.
      CONCLUSIONS: Our results reflect oxidative stress in placenta tissues of early
      pregnancy failure, as the oxidative processes seem to be counteracted by the
      physiologic activation of antioxidant enzymes such as CAT and GSH-Px. Moreover, a
      compensatory mechanism might be developed against possible oxidative damage in
      patients with miscarriage.

PMID- 16814169
TI  - Clinical characteristics of bilateral Duane syndrome.
AB  - PURPOSE: To describe the clinical characteristics of bilateral Duane syndrome.
      METHODS: Retrospective medical record review (1982 to 2003) for patients with a
      diagnosis of Duane syndrome (examined by a pediatric ophthalmologist) who were
      bilaterally affected and had no prior ocular surgery. Data collected included
      type of Duane syndrome, gender, family history for strabismus, abnormal head
      position, versions, strabismus measurements, associated ocular and/or nonocular
      abnormalities, and amblyopia status. RESULTS: Of 270 patients with the diagnosis
      of Duane syndrome, 37 (14%) were bilaterally affected. None had ocular surgery
      prior to referral. Twenty-two (59%) were male, 35 (95%) had the same Duane
      syndrome type in both eyes, 29 (78%) had strabismus in primary position, 9 (24%)
      had ocular and nonocular congenital abnormalities, 6 (16%) had amblyopia, and 8
      (22%) had a recorded strabismus family history. CONCLUSIONS: Unlike unilateral
      Duane syndrome, bilateral Duane syndrome may be more common in males and
      associated with a higher prevalence of strabismus in primary gaze position. The
      prevalences of amblyopia, positive strabismus family history, and associated
      congenital abnormalities in this series of bilateral cases is similar to the
      reported prevalence.

PMID- 16814168
TI  - Strabismus and amblyopia in bilateral Peters anomaly.
AB  - BACKGROUND: Peters anomaly is a rare form of anterior segment dysgenesis in which
      abnormal cleavage of the anterior chamber occurs at the end of the third week of
      gestation. We examined the prevalence of strabismus and amblyopia and analyzed
      predictive factors for their development, as well as the visual outcome and
      associated anomalies in patients with bilateral Peters anomaly. METHODS: Using a
      retrospective review, we identified 25 consecutive patients with bilateral Peters
      anomaly who were observed between August 1995 and February 2005. Ocular
      structural and systemic anomalies, amblyopia therapy, visual acuity, and
      binocular alignment at last visit were recorded. Fisher's exact test was used to
      identify any association between defined predictive factors and the development
      of strabismus. RESULTS: Mean follow-up time was 5.1 year (range, 0.5-21 years).
      Median age at presentation was 2.5 months (range, 1 day to 13 years). Penetrating
      keratoplasties were performed on 34 eyes in 20 patients. Final best-corrected
      visual acuity ranged from 20/25 to no light perception. Thirteen of 18 patients
      with recorded motility (72%) developed strabismus: esotropia (n = 7), exotropia
      (n = 5), and variable (n = 1); one also had dissociated vertical deviation.
      Patients with equal vision were either orthophoric (n = 4) or had intermittent
      esotropia (n = 1), whereas strabismus occurred in 100% of patients whose vision
      was asymmetric by more than 1.5 octaves. Asymmetric vision was the only
      statistically significant predictive factor for the development of strabismus (P
      = 0.002). Amblyopia treatment resulted in improved vision in 3 of 5 patients.
      CONCLUSION: Strabismus occurs frequently in bilateral Peters anomaly. Asymmetric
      vision, (because of ocular structural anomalies) postoperative complications, and
      amblyopia may predispose to strabismus. Despite ocular structural limitations,
      amblyopia therapy is recommended in the aggressive rehabilitation of these eyes.

PMID- 16814170
TI  - Ultrasound biomicroscopy in strabismus reoperations.
AB  - PURPOSE: To evaluate the accuracy of ultrasound biomicroscopy (UBM) for measuring
      the insertional distance from the limbus of horizontal extraocular muscles (EOM)
      that had previous surgery. METHODS: This prospective, masked, observational study
      compared the distance of the horizontal EOM insertion from the limbus as measured
      by 50-MHz UBM, either preoperatively or at the time of the anesthesia, with that
      measured by surgical caliper intraoperatively. RESULTS: Forty-three horizontal
      rectus muscles in 23 subjects were measured using the UBM. Of these 43 muscles,
      41 (22 medial rectus and 19 lateral rectus muscles) were successfully imaged by
      UBM and also received intraoperative surgical measurements. Two medial rectus
      muscles of one patient were inserted too far from the limbus (beyond 12 mm) to be
      detected by UBM. The mean measured distances of the horizontal muscle insertions
      from the limbus were 9.0 mm with UBM and 9.3 mm at surgery (P = 0.0001, showing
      no significant difference). For 33 (80.5%) of the muscles, the 2 methods agreed
      within 1 mm (P < 0.0001). There was no difference in accuracy for lateral rectus
      compared with medial rectus muscles or when comparing the muscles imaged by UBM
      under topical versus general anesthesia. CONCLUSION: The 50-MHz UBM can
      accurately measure the horizontal EOM insertion distances from the limbus for
      muscles in patients that had previous surgery. The limit of detection was 12 mm
      from the limbus for the MR and 14 mm for the LR. Depending on the patient's age
      and level of cooperation, the UBM study can be done under either general
      anesthesia or topical anesthesia.

PMID- 16814171
TI  - Surgical experiences with two-muscle surgery for the treatment of intermittent
      exotropia.
AB  - BACKGROUND: The surgical management of intermittent exotropia, or X(T), remains a
      challenge. Not only are some quoted success rates relatively low (40-83%), but
      the outcome is notoriously unpredictable with a tendency to exotropic drift over
      time. METHODS: In this retrospective study, 118 patients who underwent either
      bilateral lateral rectus muscle recession (BLR) or unilateral medial rectus
      muscle resection and lateral rectus muscle recession (R&R) surgery during a 4
      year period were reviewed. Surgical outcome between the 2 groups in addition to
      factors that influence outcome within groups were analyzed. Success was defined
      as an X(T) < or = 10PD. RESULTS: Sixty-four subjects underwent BLR, and 54
      subjects underwent R&R surgery. Mean preoperative distant X(T) size was 38.7 +/-
      6.7 PD. Subjects who underwent R&R did significantly better at 1-year follow-up
      (success 74.2% vs. 42.2%) but showed significantly more exotropic drift over time
      (P = 0.01). Within both BLR and R&R groups, subjects with basic-type X(T) did
      worse than those with divergence-excess X(T) at 1-year follow-up. Consecutive
      esotropias, however, were more likely with R&R surgery and in those with
      divergence excess X(T). Preoperative strabismus control, distant X(T) size, and
      patient age at surgery did not significantly influence outcome. CONCLUSION: In
      many cases, selection of surgery type continues to depend on the surgeon's
      preference, which is in turn influenced by his/her past experiences. The debate
      about which surgical type is best for different X(T) types continues.

PMID- 16814172
TI  - Age-related distance esotropia.
AB  - PURPOSE: To describe a form of acquired esotropia occurring in older adults,
      which here is termed age-related distance esotropia. METHODS: A retrospective
      consecutive case series of 26 patients with this condition was reviewed. RESULTS:
      The patients ranged in age from 62 to 91 years old with a median age of 77 years.
      The distance deviation varied from 4 prism diopters (PD) ET (esotropia) to 20 PD
      ET, with a median angle of 9 PD ET. At near fixation, the measurements ranged
      from 9 PD ET' to 10 PD X' (exophoria), with a median deviation of 3 PD ET'.
      Ductions and versions were full, with no evidence of lateral rectus paresis. None
      of these patients had an obvious underlying neurologic disorder, such as tumor or
      stroke. Treatment consisted of prescribing the minimum prismatic correction that
      eliminated distance diplopia, which was then incorporated into the patients'
      current spectacles. This treatment successfully eliminated the symptoms in all
      patients. No patient in this study required surgery. CONCLUSION: A distinctive
      form of strabismus occurs in older adults that is characterized by esotropia
      greater at distance than near fixation. The etiology of this disorder is unknown,
      but it is likely secondary to anatomical changes in the orbit and/or muscles
      associated with aging. Most patients are readily corrected by prisms but,
      surgical correction might be required in some cases.

PMID- 16814173
TI  - Superior oblique posterior tenectomy in patients with Brown syndrome with small
      deviations in the primary position.
AB  - INTRODUCTION: Procedures used to weaken the superior oblique muscle (SO) tendon
      in the treatment of patients with Brown syndrome, may result in severe
      complications, including complete SO palsy, overcorrections, foreign body
      extrusion, and scarring with limitation to ocular rotations. SO posterior
      tenectomy moderately weakens abduction and depression while preserving most of
      the torsional action of the SO muscle. PURPOSE: We sought to evaluate motor and
      sensorial results after SO posterior tenectomy in patients with Brown syndrome
      who had a small vertical deviation (less than 7 prism diopters [PD]) in primary
      position but severe limitation to elevation in adduction. METHODOLOGY: We
      retrospectively analyzed 12 consecutive patients with unilateral Brown syndrome
      who underwent a 15 mm tenectomy of the posterior four-fifths fibers of the
      ipsilateral SO tendon. Intraoperative forced duction showed restriction to
      elevation in adduction in all subjects. No patient had concomitant surgery on any
      other extraocular muscle. RESULTS: The mean patient age at diagnosis was 6.9 +/-
      1.7 years. Preoperative vertical deviation measured 4 +/- 1 PD in the primary
      position and 12 +/- 2 PD in elevation in adduction. Postoperative follow-up was
      24.7 +/- 9.2 months. Postoperatively, all patients had less than 2 PD of
      orthotropia in the primary position, and the deviation in elevation in adduction
      was significantly improved at 3 +/- 2 PD (P < 0.05). Elevation in adduction
      improved from -4.0 preoperatively to -1.9 +/- 1 postoperatively (P = 0.0000003)
      and no patient experienced underaction of the SO. Postoperatively, all patients
      had stereopsis in primary position. CONCLUSION: The use of SO posterior tenectomy
      improves alignment and ocular rotations in patients with Brown syndrome,
      resulting in fusion, small vertical deviation in primary position, and minimal-to
      no anomalous head posture, in whom the most important finding is a disfiguring
      downshoot on attempted adduction. Other advantages include minimal-to-no
      postoperative SO muscle underaction and no risk of foreign body extrusion,
      fibrosis, and scarring.

PMID- 16814174
TI  - Unilateral lateral rectus muscle recession and medial rectus muscle resection
      with or without advancement for postoperative consecutive exotropia.
AB  - PURPOSE: To evaluate the effectiveness of unilateral lateral rectus muscle
      recession and medial rectus muscle resection with or without advancement in
      treating postoperative consecutive exotropia. METHODS: We performed a
      retrospective review on 31 patients with consecutive exotropia who were treated
      with unilateral lateral rectus muscle recession and medial rectus muscle
      resection (17 patients) or unilateral lateral rectus muscle recession and medial
      rectus muscle partial resection combined with advancement (14 patients). All
      patients had exotropia with a less than 10 prism diopters (PD) distance near
      disparity. The characteristics studied before surgery included type of esotropia
      surgery, detection of amblyopia, presence of an "A" or "V" pattern, dissociated
      vertical deviation, limitation of adduction, deviation angle measurement, and
      forced duction testing. Ocular alignment and status of adduction postoperatively
      at the last follow-up were recorded. RESULTS: Nineteen patients (61.3%) had
      amblyopia, 17 patients (54.8%) had limitation of adduction, 8 patients (25.8%)
      had dissociated vertical deviation, and 5 patients (16.1%) had an "A" or "V"
      pattern. The mean preoperative exodeviation was 47.3 PD. Overall 21 (67.7%) of 31
      patients achieved a successful postoperative result (alignment within 10 PD of
      orthophoria). There was no significant difference in successful alignment in
      patients treated with unilateral medial rectus muscle resection compared with
      those treated with unilateral medial rectus muscle partial resection combined
      with advancement. There was no influence of amblyopia on the result. Twelve
      (70.6%) of the 17 patients with limited adduction preoperatively showed
      normalization of adduction postoperatively. CONCLUSIONS: Unilateral lateral
      rectus muscle recession and medial rectus muscle resection with or without
      advancement is an effective alternative for treating postoperative consecutive
      exotropia.

PMID- 16814175
TI  - The natural history of surgically untreated intermittent exotropia-looking into
      the distant future.
AB  - PURPOSE: We studied patients with distance intermittent exotropia with at least 5
      years follow-up before any surgical therapy, to determine how often amblyopia
      developed, whether there was progressive worsening in the angle or control of the
      exodeviation, whether there was deterioration in binocular vision, and other
      parameters. METHODS: Retrospective review of charts of patients with
      exodeviations examined consecutively over 17 years. RESULTS: There were 109
      patients followed for a mean of 9 years (range 5 to 25). Amblyopia was mild
      (20/25 in 33, 20/30 in 15, and 20/40 in 2). There was no significant change in
      the mean exoangle from initial to final visit (20.6 to 20.9 PD), but the initial
      to final exoangle decreased by more than 10 PD in 19%, remained stable in 58%,
      and increased by more than 10 PD in 23%. There was no statistically significant
      trend for worsening or improving when serial measurements were plotted and the
      aggregate slopes were analyzed. Change in control in the distance from initial to
      final visit was favorable in 26%, showed no change in 51%, and was unfavorable in
      23%, with 17% deteriorating to a constant distance exotropia. Mean near
      stereoacuity at the final visit was 88 seconds of arc. Strabismus surgery was
      performed in 14% of patients from 5 to 18 years (mean 9) after their initial
      visit. CONCLUSIONS: Visual acuity and near stereoacuity were generally good.
      There was little change in the mean angle of deviation from initial to final
      visit for the group, with a nearly chance occurrence for the distance deviation
      to progressively worsen or improve, perhaps explaining why strabismologists have
      had difficulty definitively prognosticating about the long-term stability of
      intermittent exotropia.

PMID- 16814176
TI  - Evaluation of the accuracy of estimation retinoscopy.
AB  - BACKGROUND: Some children are unable to cooperate for retinoscopy because they
      object strongly to the placement of lenses close to their faces. For these
      children, it would be ideal to obtain an accurate estimate of refractive error
      without using lenses. Techniques of estimation retinoscopy include sliding the
      sleeve of the Copeland retinoscope downward or moving closer to the patient until
      neutrality is achieved. The purpose of this study was to evaluate the accuracy of
      estimation techniques by comparing results to standard retinoscopy with loose
      lenses in cooperative children. METHODS: A Copeland retinoscope was calibrated
      using a schematic eye and loose lenses. A scale was created adjacent to the
      sleeve of the retinoscope which allowed an estimate of refractive error based on
      the position of the top of the sleeve. Estimation retinoscopy followed by
      standard retinoscopy with loose lenses was done on 100 eyes of 50 children after
      cycloplegia. RESULTS: Estimation of spherical equivalent for myopia less than 4 D
      and hyperopia less than 2 D correlated strongly with results obtained by standard
      retinoscopy with loose lenses (r = 0.87). Estimation retinoscopy had a
      sensitivity of 88%, specificity of 67%, positive-predictive value of 58%, and
      negative-predictive value of 92% in the detection of amblyogenic refractive
      errors. CONCLUSIONS: Estimation retinoscopy has very good accuracy for low levels
      of myopia, hyperopia, and astigmatism. Techniques of estimation may be useful in
      excluding amblyogenic refractive errors, particularly in children who object to
      loose lenses held close to them.

PMID- 16814177
TI  - Spectrum of foveal development in albinism detected with optical coherence
      tomography.
AB  - BACKGROUND: Optical coherence tomography (OCT) has shown the absence of a foveal
      depression in an individual with oculocutaneous albinism, type 1 (OCA1) and best
      corrected visual acuity (BCVA) of 20/400. However, the presence of an annular
      light reflex in the macula has been noted with indirect ophthalmoscopy in other
      patients with albinism who have better vision. We studied macular architecture in
      albinism with OCT when binocular BCVA was > or = 20/60 and compared this to
      detection of foveal development with binocular indirect ophthalmoscopy. METHODS:
      Eleven patients with albinism and BCVA > or = 20/60 were recruited for OCT.
      Average central macular thickness was recorded. Presence of an oval annular
      reflex was determined with binocular indirect ophthalmoscopy. RESULTS: Mean
      binocular BCVA was 20/39 (range: 20/20 to 20/50). Twelve eyes had a rudimentary
      annular reflex detected with ophthalmoscopy. OCT was reliable in 20 of 22 eyes. A
      foveal depression was identified with OCT in four eyes. Mean macular thickness
      for these four eyes was 233 microm (+/- 22.5 microm). We found a weak inverse
      correlation between BCVA (logMAR) and thickness (r = -0.21). CONCLUSIONS: OCT
      shows the spectrum of foveal development in albinism, from complete absence of
      development to a central depression corresponding to a rudimentary annular reflex
      detected with ophthalmoscopy. The reduced rate of detection of foveal development
      with OCT compared with ophthalmoscopy is likely related to poor fixation in
      patients with nystagmus.

PMID- 16814178
TI  - Long-term outcome of pediatric aphakic glaucoma.
AB  - PURPOSE: To determine the long-term outcome in pediatric patients with aphakic
      glaucoma. METHODS: A retrospective analysis of 130 patients diagnosed with
      aphakic glaucoma between 1969 and 2004 was performed. A total of 36 patients (55
      eyes) were included in this study after excluding those who had cataract
      extraction after age 10 and those patients with other ocular conditions, systemic
      syndromes, traumatic cataracts, congenital glaucoma, or inadequate follow-up
      (less than 1 year). Outcome variables studied included visual acuity, number of
      medication changes required over the course of the follow-up, maximum number of
      medications used at a time for more than 6 months to control intraocular
      pressures, and surgical interventions required. Mean follow-up period was 18.7
      years (range, 6.9-35 years). RESULTS: At the time of last follow-up, 54.5% of the
      patients had visual acuity 20/40 or better, 34.5% had 20/50 to 20/200, and 11%
      had acuity worse than 20/200. During the course of follow-up, 34% required 1 to 2
      medication changes for controlling glaucoma, 33% required 3 to 5 medication
      changes, and 33% required 6 or more medication changes. Thirty-six percent of the
      eyes required a maximum of 1 to 2 medications for more than 6 months during the
      course of follow-up, 33% required 3, and 31% required 4 or more medications for
      controlling intraocular pressure. Of the 55 eyes, 15 eyes (27%) required surgical
      intervention. Six of the 15 eyes (40%) required 1 surgery, 8 eyes (53%) required
      2 to 3 surgeries, and 1 eye (7%) required 4 to 6 surgeries. CONCLUSION: Patients
      with glaucoma after pediatric cataract surgery can have a good visual outcome
      although multiple medications and surgical interventions may be required to
      control the glaucoma.

PMID- 16814179
TI  - Pediatric homonymous hemianopia.
AB  - INTRODUCTION: Homonymous hemianopia is a disabling condition caused by numerous
      lesions affecting the retrochiasmal visual pathways. Little is known about
      homonymous hemianopia in childhood. METHODS: All patients seen in the Neuro
      Ophthalmology Unit at Emory University with homonymous hemianopia (confirmed by
      Goldmann, Humphrey, or confrontation visual fields) between 1989 and 2004 were
      included. Demographic characteristics, clinical features, and evolution of the
      visual field defects were compared between the pediatric group (18 years of age
      or younger) and the adult group (older than 18 years). RESULTS: Among 852
      patients with homonymous hemianopia, there were 81 children (86 homonymous
      hemianopias) and 771 adults (818 homonymous hemianopias). Formal visual field
      testing was obtained in 93% of pediatric cases and 96% of adults; a majority of
      patients in both groups were evaluated with Goldmann visual field testing.
      Demographic and visual field characteristics were similar in both groups.
      Significant differences were noted for the causative lesions and their location.
      Traumatic brain injury (34%) and tumor (27%) were the most common causes of
      homonymous hemianopia in the pediatric group, whereas infarction (63%), traumatic
      brain injury (12%), and hemorrhage (11%) were the most common causes in the adult
      group. Most lesions involved the optic radiations (37%), followed by the
      occipital lobes (26%), in the pediatric group, whereas occipital lobes (47%),
      followed by optic radiations (32%), were most commonly involved in adults.
      Approximately one third of the pediatric patients were seen in follow-up, and one
      third of these homonymous hemianopias spontaneously improved over the course of
      time. Of the 16 pediatric homonymous hemianopias evaluated within 1 month of
      onset of the cerebral disorder, 8 (50%) improved. CONCLUSION: Trauma and tumors
      are the most common cause of homonymous hemianopia in childhood. Although
      spontaneous improvement can be expected in approximately one third to one half of
      patients within the first few months, the recognition of homonymous hemianopia
      frequently is delayed in this population.

PMID- 16814180
TI  - Race, gender, and clinical risk index for babies (CRIB) score as predictors of
      severe retinopathy of prematurity.
AB  - PURPOSE: To determine whether race, gender, and the Clinical Risk Index for
      Babies (CRIB) illness severity score are predictors of threshold or severe
      prethreshold retinopathy of prematurity warranting surgery (ROP warranting
      surgery) and whether racial and gender differences in ROP are correlated with
      racial and gender differences in illness severity. METHODS: This was a
      retrospective analysis of premature infants 401-1250 g at birth that were
      admitted to the University Hospital of Cincinnati (January 1998 to May 2003).
      Birth weight, gestational age, multiple birth, birth in the study hospital or
      elsewhere, race, gender, CRIB score, and eye findings were abstracted. The
      outcome variable was ROP warranting surgery. RESULTS: Of 299 patients (596 eyes)
      with adequate eye and CRIB data, 35 patients (11.7%) [66 eyes; 11.1%] developed
      ROP warranting surgery. Multiple logistic regression analysis showed that higher
      CRIB score (P < 0.0001; odds ratio [OR] 1.21), male gender (P < 0.005; OR: 2.68),
      nonblack race (P < 0.0005; OR: 4.32), lower gestational age, and multiple birth
      are predictive factors for ROP warranting surgery. Because birth weight and
      gestational age comprise 2 of the 6 components of the CRIB score, a CRIB subscore
      (CRIBSUB) consisting of the remaining 4 components was tested and remained a
      significant predictor (P < 0.00001). Birth weight was a significant predictor
      when CRIBSUB was in the model but not when the CRIB score was used. The CRIB
      score was a predictor of neonatal mortality, but race and gender did not predict
      the CRIB score or neonatal mortality. CONCLUSIONS: Nonblack race, male gender,
      and higher CRIB illness severity scores are predictors of ROP warranting surgery.
      In our population, there were no racial or gender differences in neonatal
      mortality or CRIB scores to explain the racial and gender differences in severity
      of ROP.

PMID- 16814182
TI  - Hydrostatic pressure as an office procedure for congenital nasolacrimal duct
      obstruction.
AB  - BACKGROUND: The estimated incidence of congenital nasolacrimal duct obstruction
      (CNDO) is 5% to 20%. We examined our success rate of treating CNDO with
      hydrostatic pressure (the Crigler method) as an office procedure. METHODS: A
      total of 742 children with CNDO initially were treated noninvasively with
      hydrostatic pressure. The procedure was safely repeated up to 3 times, with an
      interval of at least 1 week, if the condition persisted. RESULTS: Success was
      defined as no epiphora or discharge. The success rate for the entire study group
      was 45% for children up to 1 year of age. The ducts were opened in 46% (343/742)
      at the first attempt of hydrostatic pressure, in 35% (42/120) at the second
      attempt, and in 38% (8/21) at the third attempt. When the maneuver was performed
      in patients younger than 2 months of age, the success rate of the first attempt
      was 56%, decreasing to 46% in children 2 to 6 months of age and to 28% older than
      6 months of age. CONCLUSIONS: Hydrostatic pressure is an effective way of
      resolving infant CNDO and shortening the duration of the associated morbidity.
      The success rate is higher when the procedure is conducted in patients up to 2
      months of age. Nevertheless, we recommend this approach for every infant
      presenting with CNDO at the first office visit, even after 6 months of age.
      Procedures can be repeated safely and successfully.

PMID- 16814181
TI  - Risk factors for amblyopia in children with capillary hemangiomas of the eyelids
      and orbit.
AB  - INTRODUCTION: Capillary hemangiomas are the most common orbital tumors of
      childhood and can cause amblyopia secondary to occlusion of the pupil,
      anisometropia, or strabismus. We undertook this study to describe the clinical
      characteristics of children with capillary hemangiomas and to propose a
      classification system to guide clinical treatment decisions. METHODS: A
      retrospective review of the records of 129 patients with 132 capillary
      hemangiomas in two pediatric ophthalmology practices was conducted. Hemangiomas
      were classified based on size. Presence of aniosometropic astigmatism, ptosis,
      pupillary occlusion, lid margin change, proptosis, globe displacement, and
      strabismus was recorded. RESULTS: Thirty-one hemangiomas measured less than 1 cm
      in greatest dimension and were not associated with amblyogenic factors. Seventy
      five patients had hemangiomas that measured greater than 1 cm, 40 of which were
      associated with amblyopia. Eighteen children had diffuse hemangiomas that could
      not be measured and 14 of these were associated with amblyopia. Five of seven
      hemangiomas in six patients with PHACES syndrome were associated with amblyopia.
      CONCLUSION: This study is the largest review of capillary hemangiomas of the
      orbit and eyelids. Our findings suggest that size greater than 1 cm in largest
      diameter is an important predictor of amblyogenic factors and approximately half
      of these patients will require treatment. Diffuse hemangiomas and hemangiomas in
      patients with PHACES syndrome will cause amblyopia in the majority of cases.

PMID- 16814183
TI  - Bilateral Duane syndrome and bilateral aniridia.
AB  - Duane retraction syndrome has been reported in association with structural
      abnormalities of the eye, including epibulbar dermoid, keratoconus, iris
      dysplasia, heterochromia iridis, persistent fetal vasculature, cataract,
      choroidal coloboma, microphthalmia, and optic nerve dysplasia. A novel
      association, that of bilateral Duane syndrome with bilateral aniridia, is the
      subject of this report.

PMID- 16814184
TI  - Fixation preference for the affected eye in patients with unilateral Duane
      syndrome.
AB  - Duane retraction syndrome is a congenital incomitant strabismus caused by
      dysinnervation of the medial and lateral rectus muscles. Patients with unilateral
      Duane syndrome (80-90% of cases) who exhibit a fixation preference tend to prefer
      the unaffected eye. We describe 8 patients with unilateral Duane syndrome who
      prefer the affected eye. The most frequent associated ophthalmic finding was
      decreased vision in the unaffected eye from anisometropia and/or amblyopia. An
      additional associated finding was decompensated intermittent exotropia in 2
      patients.

PMID- 16814185
TI  - Severe astigmatic amblyopia secondary to subcutaneous juvenile xanthogranuloma of
      the eyelid.
AB  - A number of eyelid lesions in early childhood, most commonly dacryoceles and
      hemangiomas, have been documented to cause astigmatic changes of the cornea.
      Juvenile xanthogranuloma (JXG) is typically reported to include both cutaneous
      skin and anterior ocular segment lesions. We report a case of a 10-month-old
      infant in which a subcutaneous JXG lesion of the lower eyelid resulted in
      visually significant astigmatic amblyopia.

PMID- 16814186
TI  - Blepharophimosis, ptosis, and epicanthus inversus syndrome: clinical and
      molecular analysis of a case.
AB  - Blepharophimosis-ptosis-epicanthus inversus syndrome (OMIM #U10100) is a rare
      autosomal-dominant disorder in which an eyelid malformation is associated (type
      I) or not (type H) with premature ovarian failure in the affected female. It is
      invariably characterized by 4 major features: (1) bilaterally shortened
      horizontal palpebral fissure (blepharophimosis); (2) severe impairment of the
      superior palpebral levator (ptosis); (3) a vertical skin fold arising from the
      lower eyelid, which inserts medially in the upper lid (epicanthus inversus) and
      (4) an increased inner can-thal distance with a normal outer canthal distance
      (telecanthus). The mutations causing this disorder are found in the FOXL2 gene, a
      forkhead transcription factor, located in 3q23. Although many patients with
      blepharophimosis-ptosis-epicanthus inversus syndrome have an affected parent, a
      conspicuous number of sporadic cases also have been reported. We describe here a
      sporadic case with a mutation in the FOXL2 gene that was well characterized both
      clinically and molecularly.

PMID- 16814187
TI  - A simple correction for congenital tarsal kink associated with distichiasis.
AB  - Congenital tarsal kink is a rare condition. The folded edge of the upper tarsus,
      or the inturned lashes, may traumatize the cornea causing ulceration. We describe
      a case of unilateral upper eyelid horizontal tarsal kink associated with
      distichiasis and congenital corneal ulceration. Several different surgical
      treatment options have been previously alluded to in the literature including
      lamellar tarsoplasty, full-thickness eyelid fracture, and rotation and excision
      of the kink with tarsal reapposition. Repair by means of eyelid everting sutures
      via an anterior lamellar approach is presented as a novel technique to correct
      this congenital anomaly.

PMID- 16814188
TI  - Solitary orbital infantile myofibroma: a case report and review of the
      literature.
AB  - Infantile myofibromatosis is a benign condition involving the skin, viscera, or
      bone that presents rarely in the orbit where rapid growth and bony destruction
      can mimic malignant tumors. Lesions can be solitary or scattered throughout the
      body. Growth in viscera such as the lungs can lead to death. Herein, we present a
      case of a solitary orbital myofibroma in a young child.

PMID- 16814189
TI  - Persistent fetal vasculature associated with orbital lymphangioma.
AB  - Persistent fetal vasculature (PFV), also known as persistent hyperplastic primary
      vitreous (PHPV), is a failure of regression of the primary vitreous, which
      usually occurs in isolation. Orbital lymphangiomas present in early life with
      eyelid swelling or proptosis and are not associated with intraocular
      abnormalities. We report the case of a male infant with PHPV and ipsilateral
      orbital lymphangioma.

PMID- 16814190
TI  - The surgical management of consecutive exotropia.

PMID- 16814191
TI  - The surgical management of consecutive exotropia.

PMID- 16814194
TI  - Comparison of the immediate with the 24-hour postoperative prism and cover
      measurements in adjustable muscle surgery: is immediate postoperative adjustment
      reliable?

PMID- 16814195
TI  - Exploring the material basis for health: characteristics of parks in Montreal
      neighborhoods with contrasting health outcomes.
AB  - The growing evidence of neighborhood influences on health points to the need for
      investigation of health-relevant features of local environments. This study
      examines one potentially health-enhancing neighborhood resource, urban parks, to
      test for systematic differences in material conditions between areas. Twenty
      eight parks selected from six urban Montreal neighborhoods along a health status
      gradient are qualitatively assessed. While neighborhood parks showed a variety of
      feature quality ratings, those located in poor health areas displayed several
      pronounced material disadvantages, including concentration of physical
      incivilities, limited provision of facilities for physical exercise, and
      adjacency to industrial sites and multi-lane roads. Equalizing park quality
      between areas may be an important step for public health promotion.

PMID- 16814196
TI  - Stress and social change in Poland.
AB  - The paper reports the findings of qualitative research carried out in Nowa Huta
      Krakow, which sought to explore the influences perceived to contribute to the
      experience of stress. Stress was seen as the main danger to health in transition,
      and as such a socially produced phenomenon linked to the lack of security of
      employment and low income, as well as to changing social relations, where social
      inequalities were increasing, and the enrichment of some was seen to be occurring
      at society's expense. The paper outlines a framework for conceptualising
      psychosocial health influences, where these are represented in terms specific to
      social space/time, indicating the implications of the findings for public health
      discourse.

PMID- 16814197
TI  - Where do children usually play? A qualitative study of parents' perceptions of
      influences on children's active free-play.
AB  - This study explored the perceptions of 78 parents from low, mid and high socio
      economic areas in Melbourne, Australia to increase understanding of where
      children play and why. Using an ecological model interviews with parents revealed
      that safety and social factors emerged as key social themes, facilities at parks
      and playgrounds, and urban design factors emerged as important physical
      environment themes. The children's level of independence and attitudes to active
      free-play were considered to be important individual level influences on active
      free-play. The study findings have important implications for future urban
      planning and children's opportunities for active free-play.

PMID- 16814198
TI  - What is the association between sickness absence, mortality and morbidity?
AB  - This paper examines the area-level relationships in England and Wales between
      sickness absence ('incapacity benefit'), mortality and morbidity. It uses a
      random sample of incapacity benefit claims, and population counts of mortality
      and Census morbidity for local government districts. Although there is little
      correspondence between sickness absence claims by specific cause and mortality,
      all cause sickness absence has a strong relationship with all cause mortality
      (male r 0.74, p=0.00; female r 0.64, p=0.00) and it also has a very strong
      relationship with the Census measures of morbidity: LLTI (male r 0.98, p=0.00;
      female r 0.97, p=0.00) and 'not good health' (male r 0.99, p=0.00; female r 0.96,
      p=0.00). Incapacity benefit claims by all causes has the potential to provide an
      ongoing measure of area-level health in England and Wales.

PMID- 16814199
TI  - Mechanisms of experimental resistance of Leishmania to miltefosine: Implications
      for clinical use.
AB  - Miltefosine (hexadecylphosphocholine, MIL), registered as Impavido((R)), has
      become the first oral drug for the treatment of visceral and cutaneous
      leishmanasis. MIL is a simple molecule, very stable, relatively safe and highly
      efficient in clinical trials. However, MIL requires a long treatment course (28
      days) and has a long half-life (around 150h), which might accelerate the
      emergence of drug resistance in case of inadequate use. The mechanisms of MIL
      resistance have been studied in vitro with experimental resistant lines.
      Resistance was shown to develop quickly in Leishmania promastigotes.
      Interestingly, a decreased MIL accumulation has always accounted for the
      resistance phenotype. The lower MIL accumulation can be achieved by two
      independent mechanisms: (i) an increase in drug efflux, mediated by the
      overexpression of the ABC transporter P-glycoprotein, and (ii) a decrease in drug
      uptake, which is easily achieved by the inactivation of any one of the two
      proteins known to be responsible for the MIL uptake, the MIL transporter LdMT and
      its beta subunit LdRos3. Policies concerning a proper use of this drug should be
      followed and supervised by health authorities of endemic areas to minimalize the
      risk for the appearance of drug failures and to ensure a long life span for this
      effective oral drug.

PMID- 16814201
TI  - WHO's mixed priorities.

PMID- 16814200
TI  - Sphingolipids of the nucleus and their role in nuclear signaling.
AB  - Sphingolipids have important signaling and regulatory roles in the nuclei of all
      vertebrate cells examined to date. Sphingomyelin (SM) is the most abundant of
      this group and occurs in the nuclear envelope (NE) as well as intranuclear sites.
      The primary product of SM metabolism is ceramide, whose release by nuclear
      sphingomyelinase triggers apoptosis and other metabolic changes in the nucleus.
      Further catabolism results in free fatty acid and sphingosine formation, the
      latter being capable of conversion to sphingosine phosphate by action of a
      specific nuclear kinase. Finally, glycosphingolipids such as gangliosides occur
      in the NE where GM1, one member of the gangliotetraose family, influences Ca(2+)
      flux by activation of a Na(+)/Ca(2+) exchanger located in the inner membrane of
      the NE. The tightly associated GM1/exchanger complex was shown to exert a
      cytoprotective role in neurons and other cell types, as absence of this nuclear
      complex rendered cells vulnerable to apoptosis. A striking example of this mode
      of Ca(2+) regulation is the greatly enhanced seizure activity in knockout mice
      lacking gangliotetraose gangliosides, involving programmed cell death in the CA3
      region of the hippocampus. In this model, Ca(2+) homeostasis was restored most
      effectively with LIGA-20, a membrane-permeant derivative of GM1 that entered the
      NE and activated the nuclear Na(+)/Ca(2+) exchanger.

PMID- 16814202
TI  - Keynote comment: The importance of advocating for lifesaving change.

PMID- 16814203
TI  - Is HPV testing with cytological triage a more logical approach in cervical cancer
      screening?

PMID- 16814204
TI  - Why a third attempt at legislation for physician-assisted suicide in the UK
      failed.

PMID- 16814205
TI  - Should experimental therapy be made available off-study for terminally ill
      patients?

PMID- 16814206
TI  - Human papillomavirus testing and liquid-based cytology in primary screening of
      women younger than 35 years: results at recruitment for a randomised controlled
      trial.
AB  - BACKGROUND: Testing for human papillomavirus (HPV) DNA is more sensitive but less
      specific than cytological analysis. Loss in specificity is most relevant in women
      younger than 35 years because of increased HPV prevalence. We aimed to compare
      conventional screening with an experimental strategy in women aged 25-34 years,
      and investigate the effect of different criteria of referral to define the best
      methods of HPV screening. METHODS: Women were randomly assigned to the
      conventional procedure (standard cytology, with referral to colposcopy if
      cytology showed atypical squamous cells of undetermined significance or more
      [ASCUS+]) or an experimental procedure (liquid-based cytology and testing for
      high-risk HPV types, with referral to colposcopy with ASCUS+ cytology). Women
      positive for HPV (cutoff > or = 1 pg/mL) but with normal cytology were retested
      after 1 year. The main endpoint was the presence of cervical intraepithelial
      neoplasia at grade 2 or more (CIN2+) in reviewed histology. The main analysis was
      by intention to screen. This trial is registered as an International Standard
      Randomised Controlled Trial, number ISRCTN81678807. FINDINGS: We randomly
      assigned 5808 women aged 25-34 years to the conventional group and 6002 to the
      experimental group. The experimental procedure was significantly more sensitive
      than the conventional procedure (55 vs 33 CIN2+ lesions detected; relative
      sensitivity 1.61 [95% CI 1.05-2.48]), but had a lower positive predictive value
      (PPV; relative PPV 0.55 [0.37-0.82]). HPV testing (> or = 1 pg/mL) with cytology
      triage was also more sensitive than conventional cytology (relative sensitivity
      1.58 [1.03-2.44], relative PPV 0.78 [0.52-1.16]). Relative PPV could be improved,
      with minimum loss in sensitivity, by use of a 2 pg/mL cutoff for HPV testing.
      Compared with conventional cytology, liquid-based cytology had a relative
      sensitivity of 1.32 (0.84-2.06), relative PPV 0.58 [0.38-0.89]). INTERPRETATION:
      HPV testing alone with cytology triage could be a feasible alternative to
      conventional cytology for screening women younger than 35 years. Follow-up will
      provide data on possible overdiagnosis and on the feasibility of extended
      intervals.

PMID- 16814207
TI  - Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal
      cell carcinoma: a retrospective study.
AB  - BACKGROUND: Distant metastasis is the main cause of death from renal-cell
      carcinoma, and the metastatic potential of tumours is often unpredictable. We
      aimed to investigate whether IMP3, an oncofetal RNA-binding protein, can be used
      as a biomarker to predict metastasis and prognosis of renal-cell carcinoma.
      METHODS: We studied 501 primary and metastatic renal-cell tumours. 371 patients
      with localised primary tumours were further investigated by use of survival
      analysis. We assessed IMP3 expression in tumour tissues by immunohistochemistry,
      and IMP3 mRNA and protein expression in selected tissues by quantitative real
      time PCR and western blot analysis. FINDINGS: Compared with non-metastatic renal
      cell tumours, IMP3 expression was greatly increased not only in metastatic
      tumours but also in a subset of primary tumours that were likely to subsequently
      develop metastases. Patients with primary localised tumours that did not express
      IMP3 had a longer metastasis-free survival and overall survival than did those
      with tumours expressing IMP3 (p<0.0001). Patients with IMP3-positive localised
      tumours had a much lower 5-year metastasis-free survival than did those with IMP3
      negative tumours (for stage I tumours, 44% vs 98%, hazard ratio 17.18 [95% CI
      7.82-37.78]; stage II, 41% vs 94%, 10.14 [3.46-29.68]; stage III, 16% vs 62%,
      4.04 [2.23-7.31]). IMP3 expression was also associated with reduced 5-year
      overall survival (stage I, 32% vs 89%, 6.44 [3.63-11.42]; stage II, 41% vs 88%,
      6.93 [2.63-18.27]; stage III, 14% vs 58%, 3.46 [1.98-6.05]). Multivariable
      analysis of IMP3 status (positive vs negative) in primary tumours showed hazard
      ratios of 5.84 (95% CI 3.60-9.49) for metastasis-free survival and 4.01 (2.66
      6.05) for overall survival (both p<0.0001), which were much higher than hazard
      ratios associated with other independent risk factors. INTERPRETATION: IMP3 is an
      independent prognostic marker that can be used at initial diagnosis of renal-cell
      carcinoma to identify patients who have a high potential to develop metastasis
      and who might benefit from early systemic treatment.

PMID- 16814208
TI  - Reassessment of the role of induction chemotherapy for head and neck cancer.
AB  - Head and neck cancers are a complex group of diseases defined by variations in
      histological features, anatomical location, and cause. Once the realm of surgeons
      and radiation oncologists, the treatment of locally advanced disease now involves
      medical oncologists. Major developments include primary chemoradiotherapy for
      unresectable disease and organ preservation, the addition of chemotherapy to
      adjuvant radiotherapy, improvement in surgical and radiation techniques, and
      biological therapies. Concomitant chemoradiotherapy consistently improves
      locoregional control. However, control of distant metastases is poor, resulting
      in an increasing proportion of deaths from systemic recurrence. Given this shift
      in site of recurrence, therapeutic strategies to suppress distant metastases may
      be the next goal for further improvement of survival. One approach that merits
      reassessment is the use of induction chemotherapy in the setting of locally
      advanced disease--both resectable and unresectable. In this review we summarise
      data for the use of induction chemotherapy to define better which patients will
      likely benefit from this approach now and which questions are important in the
      design of future clinical trials.

PMID- 16814209
TI  - Dispelling the myths surrounding radiotherapy for treatment of cutaneous
      melanoma.
AB  - The role of radiotherapy is well established in the management of most locally
      advanced and metastatic cancers; however, there has been reluctance to extend
      this role to melanoma. The reasons can be traced historically to in-vitro and in
      vivo data suggesting that melanomas are resistant to radiation. Current findings
      indicate that these cancers have a wide range of sensitivity to radiation that
      overlaps extensively with those for common epithelial cancers: indeed, some
      melanomas show high sensitivity to radiation. Greater incorporation of
      radiotherapy into multidisciplinary management of melanoma is important because
      of the typical natural history of the disease (a propensity for both locoregional
      recurrence and distant metastases) and its poor response to systemic treatment.
      This review will discuss these issues and preview the strategies being developed
      for radiotherapy to further improve the care of patients with melanoma.

PMID- 16814210
TI  - Role of radiotherapy in cancer control in low-income and middle-income countries.
AB  - More than half the cases of cancer in the world arise in people in low-income and
      middle-income countries. This proportion will rise to 70% by 2020. These are
      regions where the annual gross national income per person is less than 9386 US
      dollars. Radiotherapy is an essential part of the treatment of cancer. In high
      income countries, 52% of new cases of cancer should receive radiotherapy at least
      once and up to 25% might receive a second course. Because of the different
      distribution of tumour types worldwide and of the advanced stage at presentation,
      patients with cancer in low-income and middle-income regions could have a greater
      need for radiotherapy than those in high-income countries. Radiotherapy for cure
      or palliation has been shown to be cost effective. Many countries of low or
      middle income have limited access to radiotherapy, and 22 African and Asian
      countries have no service at all. In Africa in 2002, the actual supply of
      megavoltage radiotherapy machines (cobalt or linear accelerator) was only 155,
      18% of the estimated need. In the Asia-Pacific region, nearly 4 million cases of
      cancer arose in 2002. In 12 countries with available data, 1147 megavoltage
      machines were available for an estimated demand of nearly 4000 megavoltage
      machines. Eastern Europe and Latin America showed similar shortages. Strategies
      for developing services need planning at a national level and substantial
      investment for staff training and equipment. Safe and effective development of
      services would benefit from: links with established facilities in other
      countries, particularly those within the same region; access to information, such
      as free online journal access; and better education of all medical staff about
      the roles and benefits of radiotherapy.

PMID- 16814211
TI  - What should doctors know about cancer? Undergraduate medical education from a
      societal perspective.
AB  - Cancer is a major health problem, but medical undergraduate education about
      cancer leaves many practitioners ill-prepared. All practitioners need some
      knowledge of cancer. Those practising in rural areas might need more knowledge
      because of their isolation from tertiary services. We review the need for cancer
      education from the perspective of patients and clinicians, and examine the cancer
      knowledge skills and attitudes of medical undergraduates. Patients with cancer
      expect their family practitioner to be knowledgeable enough to act as their
      advocate and to be able to interpret for them the complex array of tests and
      treatments that they could face. Many oncologists think that they do not have
      adequate access to students because of entrenched attitudes within universities
      that aim to protect established teaching programmes and leave little room to
      adapt teaching to the changing needs of society. Surveys of medical
      undergraduates have shown that, over the past decade, students have less contact
      with patients and retain some misconceptions about cancer. To deliver appropriate
      standards of cancer teaching, an undergraduate programme should incorporate a
      national or international standard curriculum and a minimum number of essential
      experiences. Because assessment drives education, students' knowledge, skills,
      and attitudes relating to cancer should be assessed, and the outcomes of such
      assessment should inform the curriculum.

PMID- 16814212
TI  - Should patients be able to choose physician-assisted suicide at the end of their
      lives? For the proposal.
AB  - On May 12, 2006, members of the UK House of Lords voted against a proposed
      Assisted Dying for the Terminal Ill Bill. This Bill was put forward to "enable an
      adult who has capacity and who is suffering as a result of a terminal illness to
      receive medical assistance to die at his own considered and persistent request".
      Under this Bill, it would be lawful for a physician, or a member of the health
      care team working in conjunction with a physician, to assist a qualifying patient
      to die by prescribing drugs. In this Debate, Margaret Branthwaite, a retired
      barrister and former consultant medical practitioner, presents the case for
      physician-assisted suicide, whereas David Jeffrey, former chair of the ethics
      committee of the Association for Palliative Medicine of Great Britain and
      Ireland, presents the case against.

PMID- 16814213
TI  - A 10-year-old girl with bifocal synovial sarcoma.

PMID- 16814214
TI  - Unexpected skin reaction induced by radiotherapy after chloroquine use.

PMID- 16814215
TI  - Relapse of cervical cancer presenting as symptoms of Collet-Sicard syndrome with
      metastatic subcutaneous and adrenal deposits.

PMID- 16814216
TI  - Preserving vaginal birth: a call to action.

PMID- 16814217
TI  - After the afterbirth: a critical review of postpartum health relative to method
      of delivery.
AB  - Four million women give birth each year in the United States, yet postpartum
      health has gone largely unaddressed by researchers, clinicians, and women
      themselves. In light of rising US cesarean birth rates, a critical need exists to
      elucidate the ramifications of cesarean birth and assisted vaginal birth on
      postpartum health. This literature review explores the current state of knowledge
      on postpartum health in general and relative to method of delivery. Randomized
      trials and other published reports were selected from relevant databases and hand
      searches. The literature indicates that postpartum morbidity is widespread and
      affects the majority of women regardless of method of delivery. Women who have
      spontaneous vaginal birth experience less short- and long-term morbidity than
      women who undergo assisted vaginal birth or cesarean birth. To maximize
      postpartum health, providers of obstetric care need to protect the perineum
      during vaginal birth and avoid unnecessary cesarean deliveries. Clinicians must
      initiate the discussion about postpartum health antenatally and encourage women
      to enlist needed support early in the postpartum period. Flexibility in the
      schedule of postpartum care is essential. More research from the United States is
      warranted.

PMID- 16814218
TI  - Body mass index, midwifery intrapartum care, and childbirth lacerations.
AB  - Weight status is an important determinant of many health indices. 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 describe the relationship of body
      mass index and pregnancy weight gain to clinical intrapartum care, infant
      birthweight, and genital tract trauma with vaginal birth. Intrapartum care
      measures and labor events did not vary by maternal weight status. Overweight and
      obese women were more likely to be parous, and Hispanic or American Indian. Total
      pregnancy weight gain decreased, and infant birthweight increased as body mass
      index category increased. Obese women who gained 40 or more pounds during
      pregnancy had elevated rates of macrosomia and genital tract lacerations.

PMID- 16814219
TI  - Maternal body mass index, delivery route, and induction of labor in a midwifery
      caseload.
AB  - The purpose of this study was to identify the association between prepregnancy
      body mass index (BMI), weight gain in pregnancy, and newborn birth weight on
      route of delivery and induction of labor in patients receiving nurse-midwifery
      care. This retrospective cohort study examined the outcomes of 1500 consecutively
      delivered women who were cared for by two midwifery practices and delivered
      between January 1, 1998, and December 31, 2000. Cesarean delivery was
      significantly associated with the obese BMI (P < .001), nulliparity (P < .02),
      and newborn birth weight (P =.006). Prenatal weight gain did not have a
      significant correlation with cesarean birth (P = .24). In multivariable modeling,
      obese BMI, high newborn birth weight, nulliparity, and induction of labor
      increased the risk of cesarean birth. There was also a significant association
      between higher BMI and risk of induction of labor (P < .001). In a secondary
      analysis, obese BMI was associated with increased risk of induction in cases with
      ruptured membranes (OR 2.2; 95% CI 1.4-3.4) and postdates pregnancy (OR 2.0; 95%
      CI 1.1-3.4).

PMID- 16814220
TI  - The reality of resistance: the experiences of rural parturient women.
AB  - The closure of many local maternity services has given rise to contemporary
      realities of care for many rural parturient women in Canada, which, in turn,
      determines their experience of birth. To date, we do not have an understanding of
      the realities influencing the birthing experiences of rural parturient women.
      This qualitative investigation explored these issues with women from four rural
      British Columbian communities through semistructured interviews and focus groups.
      Women in this study articulated four realities that influenced the nature of
      their experience of birth, including geographic realities, the availability of
      local health service resources, and the influence of parity and financial
      implications of leaving the community to give birth. When these realities were
      incongruent with participants' needs in birth, participants developed strategies
      of resistance to mitigate the dissonance. Strategies included trying to time the
      birth at the referral hospital by undergoing an elective induction and seasonal
      timing of pregnancies to minimize the risk of winter travel. Some women showed up
      at the local hospital in an advanced stage of labor to avoid transfer to a
      referral center, or in some instances, had an unassisted homebirth.

PMID- 16814221
TI  - Comparison of selected outcomes of CenteringPregnancy versus traditional prenatal
      care.
AB  - The purpose of this study was to assess the effect of traditional prenatal care
      versus a group model of care, CenteringPregnancy, on maternal knowledge of
      pregnancy, social support, health locus of control, and satisfaction. The
      CenteringPregnancy model of care gives patients extended time with the provider
      in a group setting. The study used a two-group, pretest/posttest design of
      pregnant women who elected either the traditional approach to prenatal care (n =
      48) or the Centering approach (n = 50). The results of this study showed
      statistically significant differences between the groups on posttest in knowledge
      of pregnancy. For social support and health locus of control, the high scores at
      pretest contributed to a ceiling effect, which limited the potential for change.
      Additional research is needed to assess health status outcomes among women
      electing alternative approaches to prenatal care.

PMID- 16814222
TI  - Storytelling as an educational strategy for midwifery students.
AB  - This article describes the use of purposive storytelling as a creative teaching
      strategy in the nurse-midwifery education program at San Diego State University
      and the University of California, San Diego. Student evaluations over a 4-year
      period showed overwhelming support for the inclusion of storytelling into a
      weekly didactic midwifery course. Benefits, such as increased cognitive learning,
      enhanced role transition, and emotional clarification were identified in the
      students' comments. The students' comments further supported the efficacy of
      incorporating storytelling into midwifery education. A review of the literature
      confirms the growing popularity of storytelling in both health care and
      education, and a conceptual framework is also provided. Further research is
      needed to examine the benefits of this worthwhile technique in promoting
      learning, stimulating interest, and facilitating the development of critical
      thinking.

PMID- 16814223
TI  - Pregnant families' discussions on the Net--from virtual connections toward real
      life community.
AB  - The aim of this research was to analyze conversations between expectant families
      (N = 21) in Net Clinic, an Internet-based service designed for patients using
      public maternity care. The online conversations, shared opinions about
      experiences of pregnancy, and family life constituted the data for content
      analysis. The families developed a sense of virtual community, which gradually
      evolved into a real-life community, by discovering the similarity of their life
      situations and by giving parent-to-parent support for everyday life events. As a
      view of daily family life, Net Clinic offers maternity care professionals a
      deeper understanding of how to enhance safer pregnancy, birth, and growth of the
      family.

PMID- 16814224
TI  - Home-Based Life Saving Skills in Ethiopia: an update on the second phase of field
      testing.
AB  - Home-Based Life Saving Skills (HBLSS) was integrated over 3 years into a district
      level child survival project coordinated through the Ministry of Health and Save
      the Children Foundation/US in Liben Woreda, Guji Zone, Oromia Region, southern
      Ethiopia. During late 2004, the second phase of the program was reviewed for
      performance, home-based management, learning transfer, and program coverage. The
      immediate posttraining performance score for HBLSS guides for "First Actions" was
      87% (a 78% increase over the pretraining baseline) and 79% at 1 year (a 9%
      decrease from the immediate posttraining score). The home-based management score
      of women attended by HBLSS guides for "First Actions" was 89%, compared to 32%
      for women assisted by other unskilled attendants. HBLSS guides teach women and
      families in the community as they were taught, by using pictorial Take Action
      Cards, role-play and demonstration, and a variety of venues. Estimates of HBLSS
      coverage suggest that HBLSS guides attended 24% to 26% of births, and 54% of
      women giving birth were exposed to HBLSS training. The HBLSS field tests
      demonstrate a promising program that increases access to basic care for poor,
      underserved, rural populations who carry the greatest burden of maternal and
      neonatal mortality.

PMID- 16814225
TI  - Clinical implications from an exploratory study of postural management of breech
      presentation.
AB  - The results from an exploratory study of the effectiveness of maternal knee-chest
      posture for producing cephalic version of breech presentation are shown. Methods
      are briefly described and clinical implications are presented. Among 25 women,
      fewer who performed the maternal knee-chest postural intervention experienced
      fetal cephalic version than women in the control group who did nothing to
      influence breech presentation. Despite limitations of the underpowered findings,
      trends in the data may indicate that parity and gestational age were potentially
      relevant covariates of version. Postural management is not an evidence-based
      practice. This exploratory study indicates that maternal knee-chest posture may
      work opposite to the expected direction, but the small sample size precludes
      generalizations about efficacy of knee-chest postural management. At least one
      adequately powered trial that controls for parity and gestational age is needed
      to determine whether knee-chest postural management results in no effect, a
      small, or small to moderate clinically significant effect.

PMID- 16814226
TI  - A surprising case of sustained antenatal fetal bradycardia.
AB  - Persistent fetal bradycardia noted in the antenatal period can occur secondary to
      maternal conditions, fetal cardiac structural defects, or from congenital heart
      block. Fetal bradycardia can be mistaken for maternal pulse and should be
      confirmed with ultrasound whenever possible. Prompt evaluation of the fetus with
      bradycardia can lead to early interventions designed to prevent cardiac damage
      and/or hydrops.

PMID- 16814227
TI  - Theory-practice gap in student experiences.

PMID- 16814229
TI  - Planning a VBAC homebirth.

PMID- 16814231
TI  - Guidelines for Ethical Research Collaboration across International and Culturally
      Diverse Communities. The Hague: International Confederation of Midwives.

PMID- 16814233
TI  - The art of communicating.

PMID- 16814235
TI  - Central corneal thickness and normal tension glaucoma: a cross-sectional study.

PMID- 16814236
TI  - Eye injuries on the battlefields of Iraq and Afghanistan: public health
      implications.
AB  - BACKGROUND: The U.S. Army faces major challenges in balancing the need to protect
      a soldier from harm while not impeding his ability to fight. Unfortunately, the
      incidence of combat eye injuries has increased over time, despite the development
      of protective measures. METHODS: A cross-sectional study of soldiers evacuated
      from Operation Iraqi Freedom and Operation Enduring Freedom with eye injuries was
      performed from March 2003 through December 2004. Data for this study came from
      the Military Office of the Surgeon General (OTSG) Patient Tracking Database.
      RESULTS: A total of 368 patients (451 eyes) were evacuated for eye-related
      problems. From March 2003 through December 2004, 15.8% (258 of 1,635 patients,
      309 eyes) of all medical evacuations were a result of battle eye injuries (BI),
      17.3% (283 of 1,635 patients, 337 eyes) were a result of eye injuries (BI and
      nonbattle injuries [NBI] combined), and 22.5% (368 of 1,635 patients, 451 eyes)
      of all evacuations were because of eye-related complaints alone (BI, NBI, or
      disease) or in combination with other bodily injuries. CONCLUSION: Developing
      combat eye protection that meets the unique requirements of the military, issuing
      eyewear to soldiers, and supporting and enforcing its use, will provide the best
      eye protection for American soldiers during military training exercises and
      future conflicts.

PMID- 16814237
TI  - Supportive care of facial nerve palsy with temporary external eyelid weights.
AB  - BACKGROUND: Patients with facial nerve palsy can have many ocular complications.
      Lagophthalmos, or poor eyelid closure, and loss of blink secondary to lack of
      nerve supply to the orbicularis oculi, can lead to exposure keratopathy, corneal
      breakdown, ulcers, and even perforation. Management of patients should be
      directed toward the severity of ocular findings and ranges from supportive care
      to surgical reanimation and soft tissue repositioning. Patients with facial nerve
      palsy who present at earlier stages can benefit from conservative treatment. Use
      of temporary external eyelid weights can help restore a functional blink
      mechanism and prevent corneal decompensation. CASE REPORT: A 29-year-old patient
      with lagophthalmos secondary to left facial nerve palsy after surgical excision
      of an acoustic neuroma was treated with a temporary external eyelid weight.
      CONCLUSION: Temporary external eyelid weights are part of the armamentarium in
      the supportive care of patients with lagophthalmos and exposure keratopathy
      secondary to facial nerve palsy. They are most useful in patients who have
      temporary paralysis or as a bridge until further surgery can be performed.

PMID- 16814238
TI  - Revisions to tolerances in cylinder axis and in progressive addition lens power
      in ANSI Z80.1-2005.
AB  - BACKGROUND: ANSI Z80.1 (American National Standards Institute) is a voluntary
      standard that provides tolerance guidelines for ophthalmic lens parameters. The
      recently approved ANSI Z80.1-2005 changes tolerances for cylinder axis for all
      ophthalmic lenses and for distance power for progressive addition lenses (PALs).
      METHODS: The ANSI Z80.1 committee analyzed the amount of unwanted residual
      cylinder created by rotating a cylinder axis away from its desired orientation
      for a range of cylinder powers. The limits of axis orientation error that keep
      the residual unwanted cylinder error within the tolerances for cylinder power
      were determined. For PALs, a tolerance for distance power error was sought that
      considers the currently followed standards for front surface power error and the
      tooling steps used for the rear surface. RESULTS: Tolerances for cylinder axis
      error were changed to +/-14 degrees for 0.25 diopter (D) cylinders and to +/-7
      degrees for 0.50 D cylinders. Tolerance for error in back vertex power of PALs
      was changed to +/-0.16 D for both sphere and cylinder. CONCLUSION: Tolerances for
      cylinder axis for low cylinders have been made in ANSI Z80.1-2005 to be
      consistent with tolerances in cylinder power. Changes in tolerance for power
      errors in PALs have been made to recognize fabrication challenges.

PMID- 16814239
TI  - A combination solution for routine pupillary dilation.
AB  - BACKGROUND: This study investigated the ability of a combination drop containing
      reduced concentrations of tropicamide and phenylephrine to produce pupillary
      dilation adequate for routine fundoscopy. METHODS: One eye of each subject (N =
      28; age range, 21 to 40 years; median, 23 years) was dilated with 1 drop of a
      solution containing 0.5% tropicamide and 2.5% phenylephrine (0.5T/2.5P). The
      other eye was dilated with 1 drop of either of 2 mixtures: 0.5% tropicamide and
      1.25% phenylephrine (0.5T/1.25P, N = 15; median age, 23 years), or 0.25%
      tropicamide and 1.25% phenylephrine (0.25T/1.25P, N = 13; median age, 23 years).
      A topical anesthetic was administered before instilling the mydriatic agents.
      Pupil diameter was measured from a flash photograph taken every 15 minutes for 3
      hours. There was no significant difference in pupil diameter between eyes dilated
      with the 0.5T/1.25P test solution and the 0.5T/2.5P control solution for the
      first 75 minutes after instillation (P = 0.41). All pupils reached their maximum
      diameter 60 minutes after drop instillation; where no significant difference was
      observed between the 3 mydriatic solutions (P = 0.81). All pupils were at least 7
      mm in diameter 30 minutes after drop instillation, and this size was maintained
      for at least another 75 minutes for all solutions. CONCLUSIONS: Combination
      preparations of reduced concentrations of tropicamide and phenylephrine can
      produce clinically adequate mydriasis.

PMID- 16814240
TI  - Spreading on and penetration into thin, permeable print media: application to ink
      jet printing.
AB  - This paper examines spreading and penetration of surfactant-laden drops on thin
      permeable media with reference to ink-jet printing. A detailed review of the
      interaction of both pure liquids and surfactant containing solutions with porous
      substrates is given for individual spreading and penetration and for the combined
      processes. A new model based on energy arguments is derived and compared to
      current hydrodynamic equations used to describe simultaneous spreading and
      penetration. Three studies of how surfactant solutions interact with thin
      commercial ink-jet photographic quality papers are presented. Here, two relevant
      systems are examined: Tergitol 15-S-5 and 1,2-octanediol. The first study
      examines the spreading and penetration profiles for surfactant solutions over a
      range of concentrations spanning their critical micelle concentration. As
      expected, these profiles depend on the concentration of surfactant and the
      chemistry of the medium with which it interacts. In many cases, partial vertical
      penetration of the region directly beneath the drop dominates at low interaction
      times and will be significant in ink-jet applications. The second study consists
      of a parametric investigation of the energy-based model derived herein. It shows
      that the model can capture all of the behaviors observed in the first study. In
      the final study, the ability of the energy-based model to fully predict the
      spreading behavior of Tergitol 15-S-5 solutions is tested. It is found that the
      model produces good quantitative agreement at the highest concentrations and, as
      such, will be useful in screening spreading dynamics concentrated systems like
      ink-jet inks. Agreement at low to intermediate concentrations is often limited by
      finite induction periods prior to significant spreading and penetration. Possible
      corrections that could improve the agreement for weakly concentrated solutions
      are discussed, and directions for future studies of simultaneous spreading and
      penetration are proposed.

PMID- 16814241
TI  - Voltammetric determination of gamma radiation-induced DNA damage.
AB  - Homopolydeoxyribonucleotides, poly[dGuo], poly[dAdo], poly[dThd], and poly[dCyd],
      and calf thymus single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA)
      aqueous solutions previously exposed to gamma radiation doses between 2 and 35
      Gy, were studied by differential pulse voltammetry using a glassy carbon
      electrode. The interpretation of the voltammetric data was also supported by the
      electrophoretic migration profile obtained for the same ssDNA and dsDNA gamma
      irradiated samples by nondenaturing agarose gel electrophoresis. The generation
      of 8-oxo-7,8-dihydroguanine, 2,8-dihydroxyadenine, 5-formyluracil, base-free
      sites, and single- and double-stranded breaks in the gamma-irradiated DNA samples
      was detected voltammetrically, with the amount depending on the irradiation time.
      It was found that the current peaks obtained for 8-oxoguanine increase linearly
      with the radiation dose applied to the nucleic acid sample, and values between 8
      and 446 8-oxo-7,8-dihydroguanine (8-oxoGua) per 10(6) guanines per Gy were
      obtained according to the nucleic acid sample. The results showed that
      voltammetry can be used for monitoring and simultaneously characterizing
      different kinds of DNA damage caused by gamma radiation exposure.

PMID- 16814243
TI  - A microtiter plate fraction collector for the sequencing of radioactive
      phosphorylated peptides.

PMID- 16814242
TI  - Application of phosphoinositide-binding domains for the detection and
      quantification of specific phosphoinositides.
AB  - In mammals, seven phosphoinositides are known to play crucial roles as signaling
      molecules in a variety of cellular processes. Their synthesis and degradation are
      thought to be strictly controlled by metabolic enzymes such as phosphoinositide
      kinases and phosphatases, and their aberrant activities cause diseases. Thus,
      there is great interest in convenient and high-throughput measurement of such
      activities for the screening of drugs that enhance or block them. To date,
      radioactive labeling and colorimetric detection of released inorganic phosphates
      are mainly used to measure phosphoinositide kinase and phosphatase activities,
      respectively. Here, we describe a novel method for detecting and quantifying
      individual phosphoinositides via phosphoinositide-binding domains that exhibit
      high specificity and affinity toward this lipid. Enzyme-linked immunosorbent
      assay wells are modified with alkyl chains (C16), which enables more uniform and
      quantitative immobilization of phosphoinositide-containing liposomes onto the
      well surfaces. Phosphoinositides, as the substrate or the product, are detected
      by pleckstrin homology domains that specifically bind to each phosphoinositide.
      By this method, phosphoinositide contents are measured with higher sensitivities
      than those by conventional methods. More importantly, both phosphoinositide
      kinase and phosphatase activities can be measured for purified enzymes and crude
      cellular lysates. This assay is easy, sensitive, and quantitative and thus may
      have a variety of applications in the development of diagnostic tests or the
      screening of therapeutic treatments for diseases such as cancer and diabetes
      which may be caused by abnormal phosphoinositide metabolism.

PMID- 16814244
TI  - Modified His-tag fusion vector for enhanced protein purification by immobilized
      metal affinity chromatography.

PMID- 16814245
TI  - Modern human molar enamel thickness and enamel-dentine junction shape.
AB  - This study examines cross-sections of molar crowns in a diverse modern human
      sample to quantify variation in enamel thickness and enamel-dentine junction
      (EDJ) shape. Histological sections were generated from molars sectioned
      buccolingually across mesial cusps. Enamel cap area, dentine area, EDJ length,
      and bi-cervical diameter were measured on micrographs using a digitizing tablet.
      Nine landmarks along the EDJ were defined, and X and Y coordinates were digitized
      in order to quantify EDJ shape. Upper molars show greater values for the
      components of enamel thickness, leading to significantly greater average enamel
      thickness than in lower molars. Average enamel thickness increased significantly
      from M1 to M3 in both molar rows, due to significantly increasing enamel cap area
      in upper molars, and decreasing dentine area in lower molars. Differences in EDJ
      shape were found among maxillary molars in combined and individual populations.
      Sex differences were also found; males showed significantly greater dentine area,
      EDJ length, and bi-cervical diameters in certain tooth types, which resulted in
      females having significantly thicker average enamel. Differences in enamel
      thickness and EDJ shape within molars were also found among populations, although
      few consistent trends were evident. This study demonstrates that enamel thickness
      and EDJ shape vary among molars, between sexes, and among populations; these
      factors must be considered in the categorization and comparison of ape and human
      molars, particularly when isolated teeth or fossil taxa are included. Human
      relative enamel thickness encompasses most values reported for fossil apes and
      humans, suggesting limited taxonomic value when considered alone.

PMID- 16814246
TI  - Mitochondrial dysfunction in hepatitis C virus infection.
AB  - The mechanisms of liver injury in chronic hepatitis C virus (HCV) infection are
      poorly understood though HCV induces a state of hepatic oxidative stress that is
      more pronounced than that present in many other inflammatory diseases. This mini
      review will focus on recent findings revealing an unexpected role of mitochondria
      in providing a central role in the innate immunity and in addition will
      illustrate the application of stably transfected human-derived cell lines,
      inducibly expressing the entire HCV open reading frame for in vitro studies on
      mitochondria. Results obtained by a comparative analysis of the respiratory chain
      complexes activities along with mitochondrial morpho-functional confocal
      microscopy imaging show a detrimental effect of HCV proteins on the cell
      oxidative metabolism with specific inhibition of complex I activity, decrease of
      mtDeltaPsi, increased production of reactive oxygen species. A possible de
      regulation of calcium recycling between the endoplasmic reticulum and the
      mitochondrial network is discussed to provide new insights in the pathogenesis of
      hepatitis C.

PMID- 16814247
TI  - Fatty acid activation of the uncoupling proteins requires the presence of the
      central matrix loop from UCP1.
AB  - Noradrenaline signals the initiation of brown fat thermogenesis and the fatty
      acids liberated by the hormone-stimulated lipolysis act as second messengers to
      activate the uncoupling protein UCP1. UCP1 is a mitochondrial transporter that
      catalyses the re-entry of protons to the mitochondrial matrix thus allowing a
      regulated discharge of the proton gradient. The high affinity of UCP1 for fatty
      acids is a distinct feature of this uncoupling protein. The uncoupling proteins
      belong to a protein superfamily formed by the mitochondrial metabolite carriers.
      Members of this family present a tripartite structure where a domain containing
      two transmembrane helices, linked by a long hydrophilic loop, is repeated three
      times. Using protein chimeras, where the repeats had been swapped between UCP1
      and UCP3, it has been shown that the central third of UCP1 is necessary and
      sufficient for the response of the protein to fatty acids. We have extended those
      studies and in the present report we have generated protein chimeras where
      different regions of the second repeat of UCP1 have been sequentially replaced
      with their UCP2 counterparts. The resulting chimeras present a progressive
      degradation of the characteristic bioenergetic properties of UCP1. We demonstrate
      that the presence of the second matrix loop is necessary for the high affinity
      activation of UCP1 by fatty acids.

PMID- 16814248
TI  - Acetyl-L-carnitine feeding to unloaded rats triggers in soleus muscle the
      coordinated expression of genes involved in mitochondrial biogenesis.
AB  - The expressional profile of mitochondrial transcripts and of genes involved in
      the mitochondrial biogenesis pathway induced by ALCAR daily supplementation in
      soleus muscle of control and unloaded 3-month-old rats has been analyzed. It has
      been found that ALCAR treatment is able to upregulate the expression level of
      mitochondrial transcripts (COX I, ATP6, ND6, 16 S rRNA) in both control and
      unloaded animals. Interestingly, ALCAR feeding to unloaded rats resulted in the
      increase of transcript level for master factors involved in mitochondrial
      biogenesis (PGC-1alpha, NRF-1, TFAM). It also prevented the unloading-induced
      downregulation of mRNA levels for kinases able to transduce metabolic (AMPK) and
      neuronal stimuli (CaMKIIbeta) into mitochondrial biogenesis. No significant
      effect on the expressional level of such genes was found in control ALCAR-treated
      rats. In addition, ALCAR feeding was able to prevent the loss of mitochondrial
      protein content due to unloading condition. Correlation analysis revealed a
      strong coordination in the expression of genes involved in mitochondrial
      biogenesis only in ALCAR-treated suspended animals, supporting a differentiated
      effect of ALCAR treatment in relation to the loading state of the soleus muscle.
      In conclusions, we demonstrated the ability of ALCAR supplementation to promote
      only in soleus muscle of hindlimb suspended rats an orchestrated expression of
      genes involved in mitochondrial biogenesis, which might counteract the unloading
      induced metabolic changes, preventing the loss of mitochondrial proteins.

PMID- 16814249
TI  - Reduced expression of the Tslc1 gene and its aberrant DNA methylation in rat lung
      tumors.
AB  - TSLC1 gene inactivation due to promoter methylation has been reported in several
      human cancers. Here, we investigated the expression of the Tslc1 gene and its
      methylation pattern in lung adenocarcinomas induced by N-nitrosobis(2
      hydroxypropyl)amine (BHP). Six-week-old male Wistar rats were given 2000 ppm BHP
      in their drinking water for 12 weeks and maintained without further treatment
      until they were sacrificed at 25 weeks. Total RNA was extracted from a total of
      11 lung adenocarcinomas and their Tslc1 gene expressions were analyzed by real
      time quantitative reverse transcription-polymerase chain reaction. Tslc1
      expression was significantly reduced in the lung adenocarcinomas compared with
      three normal lung tissues (p < 0.05). Bisulfite sequence analysis of four lung
      adenocarcinomas and two normal lung tissues revealed that the 5' upstream region
      of the Tslc1 gene was highly methylated in the four lung adenocarcinomas, but
      unmethylated in the two normal lung tissues. These results suggest that aberrant
      Tslc1 gene methylation may be involved in BHP-induced development of lung
      adenocarcinomas in rats.

PMID- 16814250
TI  - p73-dependent induction of 14-3-3sigma increases the chemo-sensitivity of drug
      resistant human breast cancers.
AB  - It has been well documented that tumor suppressor p53 is mutated in about 50% of
      all human tumors. p53 status might be one of the critical determinants for the
      chemo-sensitivity of human tumors. In the present study, we have found that p53
      family member p73 as well as 14-3-3sigma is down-regulated in response to
      adriamycin (ADR) in ADR-resistant human breast cancer-derived MBA-MD-436 cells
      which carry p53 mutation. Like p53, 14-3-3sigma was transactivated by p73 and, in
      turn, stabilized p73. Luciferase reporter analysis and colony formation assays
      demonstrated that 14-3-3sigma has an ability to enhance the p73-mediated
      transcriptional activity as well as its pro-apoptotic function. Furthermore,
      enforced expression of 14-3-3sigma increased the ADR sensitivity of MBA-MD-436
      cells. Taken together, our present results strongly suggest that p73-dependent
      induction of 14-3-3sigma plays an important role in the regulation of chemo
      sensitivity of breast cancers bearing p53 mutation.

PMID- 16814251
TI  - Long-term high-fat diet induces pancreatic injuries via pancreatic
      microcirculatory disturbances and oxidative stress in rats with hyperlipidemia.
AB  - Relations between hyperlipidemia and chronic pancreatitis remain unclear.
      Microcirculatory disturbances and oxidative stress are involved in pathogeneses
      of a high numbers of diseases. The objective of this study was to induce
      hyperlipidemia in rats by long-term high-fat diet intake, then investigate the
      biochemical, microcirculatory, and histological alterations in blood and
      pancreatic tissues of these animals, and discuss their potential significances.
      Pancreatic blood flow was detected by intravital microscope; malondialdehyde
      (MDA) content and superoxide dismutase (SOD) activity were measured in pancreatic
      tissues for assessment of oxidative stress and alpha-smooth muscle actin (alpha
      SMA) expression was determined by immunohistochemical staining and RT-PCR. The
      results showed that the velocity of pancreatic microvascular blood flow of rats
      with hyperlipidemia decreased significantly as compared to control value (p =
      0.008). Pancreatic MDA content increased whereas SOD activity decreased in these
      rats (p = 0.022; p = 0.039, respectively). Histologically, microvesicles in
      acinar and islet cells, dilated rough endoplasmic reticulum, swollen
      mitochondrion and modified vascular endothelial cells were observed under light
      microscope and transmission electron microscope. In addition, alpha-SMA
      expression was up-regulated significantly (p < 0.05). These results suggest that
      long-term high-fat diet can induce chronic pancreatic injuries which could be
      considered as "nonalcoholic fatty pancreatic disease", and pancreatic
      microcirculatory disturbances and oxidative stress may play an important part in
      the underlying pathogenesis.

PMID- 16814252
TI  - The Rad9 protein enhances survival and promotes DNA repair following exposure to
      ionizing radiation.
AB  - Following DNA damage cells initiate cell cycle checkpoints to allow time to
      repair sustained lesions. Rad9, Rad1, and Hus1 proteins form a toroidal complex,
      termed the 9-1-1 complex, that is involved in checkpoint signaling. 9-1-1 shares
      high structural similarity to the DNA replication protein proliferating cell
      nuclear antigen (PCNA) and 9-1-1 has been shown in vitro to stimulate steps of
      the repair process known as long patch base excision repair. Using a system that
      allows conditional repression of the Rad9 protein in human cell culture, we show
      that Rad9, and by extension, the 9-1-1 complex, enhances cell survival, is
      required for efficient exit from G2-phase arrest, and stimulates the repair of
      damaged DNA following ionizing radiation. These data provide in vivo evidence
      that the human 9-1-1 complex participates in DNA repair in addition to its
      previously described role in DNA damage sensing.

PMID- 16814253
TI  - Characterization of a second ligand binding site of the insulin receptor.
AB  - Insulin binding to its receptor is characterized by high affinity, curvilinear
      Scatchard plots, and negative cooperativity. These properties may be the
      consequence of binding of insulin to two receptor binding sites. The N-terminal
      L1 domain and the C-terminus of the alpha subunit contain one binding site. To
      locate a second site, we examined the binding properties of chimeric receptors in
      which the L1 and L2 domains and the first Fibronectin Type III repeat of the
      insulin-like growth factor-I receptor were replaced by corresponding regions of
      the insulin receptor. Substitutions of the L2 domain and the first Fibronectin
      Type III repeat together with the L1 domain produced 80- and 300-fold increases
      in affinity for insulin. Fusion of these domains to human immunoglobulin Fc
      fragment produced a protein which bound insulin with a K(d) of 2.9 nM. These data
      strongly suggest that these domains contain an insulin binding site.

PMID- 16814254
TI  - Tumor cells with B7.1 and transmembrane anchored staphylococcal enterotoxin A
      generate effective antitumor immunity.
AB  - Staphylococcus enterotoxin A (SEA) stimulates T cells bearing certain TCR beta
      chain variable regions, when bound to MHC-II molecules, and is a potent inducer
      of CTL activity and cytokines production. To decrease toxicity of SEA to the
      normal MHC-II(+) cells and to localize the immune response induced by SEA to the
      tumor site, my colleague previously genetically fused SEA with B7.1 transmembrane
      region (named as SEAtm) to make SEA express on the surface of tumor cells and
      tumor cells modified with SEAtm could induce efficient antitumor immunity in
      vitro. The tumor cell vaccines modified with multiple immune activators
      frequently elicited stronger antitumor immune responses than single-modified
      vaccines. In this study, we modified the tumor cell vaccine with B7.1 and SEAtm
      to improve efficiency in the application of SEA. First, SEAtm gene was subcloned
      from recombinant plasmid pLXSNSEP by PCR and murine B7.1 gene was cloned from
      splenocytes derived from C57BL/6 mice by RT-PCR. Then, the eukaryotic co
      expression vector of SEA and murine B7.1 gene was constructed and named as pcDNA
      BIS. B16 cell lines stably expressing SEA and/or B7.1 were established by
      screening with G418 after transfection and inactivated for the preparation of
      tumor cell vaccines to treat mice bearing established B16 tumors. The results
      indicated that the dual-modified tumor cell vaccine B16/B7.1+SEAtm (B16-BIS)
      elicited significantly stronger antitumor immune responses in vivo when compared
      with the single-modified tumor cell vaccines B16/B7.1 (B16-B7.1) and B16/SEAtm
      (B16-SEAtm), and supported the feasibility and effectiveness of the dual-modified
      tumor cell vaccine with superantigen and co-stimulatory molecule.

PMID- 16814255
TI  - TLR4 expression in mouse embryonic stem cells and in stem cell-derived vascular
      cells is regulated by epigenetic modifications.
AB  - Embryonic stem (ES) cells and ES cell-derived differentiated cells can be used in
      tissue regeneration approaches. However, inflammation may pose a major hurdle. To
      define the inflammatory response of ES and ES cell-derived vascular cells, we
      exposed these cells to LPS. With the exception of MIF no significant cytokine
      mRNA levels were observed either at baseline or after stimulation. Further
      experiments revealed that these cells do not express TLR4. Analysis of the DNA
      methylation status of the TLR4 upstream region showed increased methylation.
      Moreover, in vitro methylation suppressed TLR4 promoter activity in reporter gene
      assays. ChIP assays showed that in this region histones H3 and H4 are
      hypoacetylated in ES cells. Interestingly, 5-aza-dC or TSA partially relieves
      this gene repression. Finally, the increased levels of TLR4 observed in ES cells
      after treatment with 5-aza-dC or TSA confer responsiveness to LPS, as induction
      of IL-6 and TNFalpha mRNA was detected in endotoxin stimulated ES cells.

PMID- 16814256
TI  - Adiponectin protects human neuroblastoma SH-SY5Y cells against acetaldehyde
      induced cytotoxicity.
AB  - Acetaldehyde, an inhibitor of mitochondrial function, has been widely used as a
      neurotoxin because it elicits a severe Parkinson's disease-like syndrome with
      elevation of the intracellular reactive oxygen species (ROS) level and apoptosis.
      Adiponectin, secreted from adipose tissue, mediates systemic insulin sensitivity
      with liver and muscle as target organs. In this study, we investigated the
      protective effects of adiponectin on acetaldehyde-induced apoptosis in human
      neuroblastoma SH-SY5Y cells and attempted to examine its mechanism. Acetaldehyde
      induced apoptosis was moderately reversed by adiponectin treatment. Our results
      suggest that the protective effects of adiponectin on acetaldehyde-induced
      apoptosis may be ascribed to ability to induce the expression of anti-oxidant
      enzymes and to regulate Bcl-2 and Bax expression. These data indicate that
      adiponectin may provide a useful therapeutic strategy for the prevention of
      progressive neurodegenerative disease such as Parkinson's disease.

PMID- 16814257
TI  - Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in
      the treatment of bipolar depression and rapid cycling bipolar disorder.
AB  - BACKGROUND: The results of pilot trials suggest that omega-3 fatty acids may have
      efficacy in the treatment of mood symptoms in bipolar disorder. METHODS: We
      conducted a 4-month, randomized, placebo-controlled, adjunctive trial of ethyl
      eicosapentanoate (EPA) 6 g/day in the treatment of bipolar depression and rapid
      cycling bipolar disorder. Subjects were receiving mood-stabilizing medications at
      therapeutic doses or plasma concentrations. The measures of efficacy were early
      study discontinuation, changes from baseline in depressive symptoms (Inventory
      for Depressive Symptomology total score) and in manic symptoms (Young Mania
      Rating Scale total score), and manic exacerbations ("switches"). We also measured
      side effects and bleeding time, a biomarker of drug action. RESULTS: Overall,
      there were no significant differences on any outcome measure between the EPA and
      placebo groups. CONCLUSIONS: This study did not find overall evidence of efficacy
      for adjunctive treatment with EPA 6 g/day in outpatients with bipolar depression
      or rapid cycling bipolar disorder.

PMID- 16814258
TI  - Depressive behavior in mice due to immune stimulation is accompanied by reduced
      neural activity in brain regions involved in positively motivated behavior.
AB  - BACKGROUND: Immune stimulation inhibits positively motivated behavior and induces
      depressive illness. To help clarify the mechanism of these effects, neural
      activity in response to a positive stimulus was examined in brain regions
      associated with positively motivated activity defined on the basis of prior
      behavioral studies of central alpha1-adrenoceptor action. METHODS: Mice
      pretreated with either lipopolysaccharide or, for comparison, reserpine were
      exposed to a motivating stimulus (fresh cage) and subsequently assayed for fos
      expression and mitogen-activated protein kinase (MAPK) phosphorylation, two
      measures associated with alpha1-adrenoceptor-dependent neural activity, in
      several positive-activity-related (motor, piriform, cingulate cortex, nucleus
      accumbens, locus coeruleus) and stress-related brain regions (paraventricular
      hypothalamus, bed nucleus stria terminalis). RESULTS: Both lipopolysaccharide and
      reserpine pretreatment abolished fresh cage-induced fos expression and MAPK
      activation in the positive activity-related brain regions but enhanced these
      measures in the stress-related areas. CONCLUSIONS: The results support the
      hypothesis that immune activation reduces alpha1-adrenoceptor-related signaling
      and neural activity in brain regions associated with positive activity while it
      increases these functions in stress-associated areas. It is suggested that neural
      activities of these two types of brain regions are mutually antagonistic and that
      a reciprocal shift toward the stress regions is a factor in the loss of
      positively motivated behaviors in sickness behavior and depressive illness.

PMID- 16814259
TI  - Why the use of benzodiazepines a few minutes before the imaging does not affect
      cerebral blood flow results in single photon emission computed studies.

PMID- 16814260
TI  - Upregulation of striatal dopamine-2 receptors in Brattleboro rats with prepulse
      inhibition deficits.
AB  - BACKGROUND: Brattleboro rats (BRATs) have natural deficits in prepulse inhibition
      (PPI) of the startle response similar to those exhibited by schizophrenia
      patients, which are reversed by antipsychotics. We sought to determine whether
      they also have increases in striatal dopamine-2 (D2) receptors found in some
      studies examining the brains of schizophrenia patients. METHODS: Several days
      after startle testing, the brains of BRAT and Long Evans (LE) rats were removed,
      and D1 and D2 receptor levels were measured by autoradiography. RESULTS: PPI was
      lower in BRATs consistent with previous reports. D2, but not D1, receptor binding
      was significantly higher in the nucleus accumbens shell and the dorsomedial
      caudate of BRAT compared with LE rats, consistent with some findings in
      schizophrenia patients. Furthermore, individual rat PPI was inversely correlated
      with D2 binding density. CONCLUSIONS: These findings suggest that the dopamine
      system in BRATs is dysregulated and these abnormalities may contribute to the PPI
      deficits observed in these rats.

PMID- 16814261
TI  - MAOA and the "cycle of violence:" childhood abuse and neglect, MAOA genotype, and
      risk for violent and antisocial behavior.
AB  - BACKGROUND: Two recent studies with white males have shown that genotypes
      associated with high levels of monamine oxidase A (MAOA) protect against the
      impact of childhood maltreatment and adversity on the development of antisocial
      behavior and conduct disorder. METHODS: Participants in a prospective cohort
      design study involving court substantiated cases of child abuse and neglect and a
      matched comparison group were followed up into adulthood and interviewed (N =
      802). Eighty-two percent consented to provide blood and 631 gave permission for
      DNA extraction and analyses. A composite index of violent and antisocial behavior
      (VASB) was created based on arrest, self-report, and diagnostic information.
      RESULTS: No main effect was found for the relationship between MAOA genotype and
      VASB. Genotypes associated with high levels of MAOA activity buffered abused and
      neglected whites from increased risk of becoming violent and/or antisocial in
      later life. This protective effect was not found for non-white abused and
      neglected individuals. CONCLUSIONS: Possible explanations for this differential
      effect for whites and non-whites include differences in contextual factors (e.g.,
      environmental stressors) and a question of the suitability of using the MAOA
      promoter VNTR polymorphism as a proxy for MAOA levels in non-white populations.

PMID- 16814262
TI  - Chronic nicotine doses down-regulate PDE4 isoforms that are targets of
      antidepressants in adolescent female rats.
AB  - BACKGROUND: Previous data in humans and animal models has suggested connections
      between anxiety, depression, smoking behavior, and nicotine dependence. The
      importance of these connections has been confirmed by clinical studies that led
      to the recent FDA approval of an anti-depressant (Zyban) for use in human smoking
      cessation programs. Other anti-depressants (such as rolipram) specifically
      inhibit PDE4 phosphodiesterases. METHODS: We used DNA microarrays to discover
      gene expression changes in adolescent female rats following chronic nicotine
      treatments, and real-time PCR assays to confirm and extend those results.
      RESULTS: We found a consistent decrease in the mRNA levels encoded by the Pde4b
      gene in nucleus accumbens, prefrontal cortex, and hippocampus of adolescent
      female rats treated with .24 mg/day nicotine, and in prefrontal cortex of
      adolescent female rats treated with .12 mg/day nicotine. We further show that
      each of these brain areas produced a different profile of Pde4b isoforms.
      CONCLUSIONS: Chronic nicotine treatments produce a dose-dependent down-regulation
      of Pde4b, which may have an antidepressant effect. This is the first report of a
      link between nicotine dependence and phosphodiesterase gene expression. Our
      results also add to the complex interrelationships between smoking and
      schizophrenia, because mutations in the PDE4B gene are associated with
      schizophrenia.

PMID- 16814263
TI  - Differential expression of disrupted-in-schizophrenia (DISC1) in bipolar
      disorder.
AB  - BACKGROUND: The disruption of the disrupted-in-schizophrenia (DISC1) gene
      segregates with major mental illnesses in a Scottish family. Association of DISC1
      with schizophrenia has been reported in several ethnic groups, and now recently
      with mood disorder. METHODS: A family-based association study of DISC1 and
      bipolar disorder (BP) in 57 bipolar pedigrees was conducted. Then, we examined
      possible association of bipolar disorder with DISC1 mRNA expression in human
      lymphoblasts. We also studied the correlation of several clinical features with
      the levels of DISC1 mRNA expression. RESULTS: Haplotype analysis identified one
      haplotype (HP1) that was overtransmitted to the BP phenotype (p = .01) and a
      second haplotype that was undertransmitted (HP2). There was a gender influence in
      the transmission distortion, with overtransmission of HP1 to affected females (p
      = .004). A significant decrease in DISC1 mRNA expression was observed in
      lymphoblasts from affected HP1 group compared to those from unaffected subjects
      with the HP2 (p = .006). Further, a higher number of manic symptoms correlated
      with lower levels of DISC1 expression (p = .008). CONCLUSIONS: These results
      suggest that decreased mRNA levels of DISC1 expression, associating with the risk
      haplotype, may be implicated in the pathophysiology of bipolar disorder.

PMID- 16814265
TI  - Growing axons in fish optic nerve are accompanied by astrocytes interconnected by
      tight junctions.
AB  - Mammalian astrocytes are in general interconnected by gap but not by tight
      junctions and play an ambiguous and controversially discussed role in central
      nervous system regeneration. At different neuroanatomical sites, fish astrocytes
      are interconnected by tight junctions and desmosomes and are involved in the
      successful regeneration of lesioned fiber tracts. In fish, newly generated
      retinal ganglion cells continuously grow new axons to the optic tectum but the
      interrelationship between glial tight junctions and axonal growth is undefined so
      far. We therefore investigated the occurrence of tight junctional structures and
      molecules within the ribbon-shaped optic nerve of a teleost fish (Astatotilapia
      burtoni) and found a predominant expression of zonula occludens protein-1 and
      claudin-1 in astrocytes where axons of new ganglion cells are assembled
      retinotopically within the optic nerve. This may support a previously formulated
      hypothesis according to that different properties of astrocytic membranes could
      be responsible for different glio-neuronal interactions which in turn may
      determine the micro-environmental conditions of growing axons.

PMID- 16814264
TI  - Associative memory encoding and recognition in schizophrenia: an event-related
      fMRI study.
AB  - BACKGROUND: We used an event-related functional Magnetic Resonance Imaging (fMRI)
      approach to examine the neural basis of the selective associative memory deficit
      in schizophrenia. METHODS: Fifteen people with schizophrenia and 18 controls were
      scanned during a pair and item memory encoding and recognition task. During
      encoding, subjects studied items and pairs of visual objects. In a subsequent
      retrieval task, participants performed an item recognition memory test (old/new
      decisions) and an associative recognition test (intact/rearranged decisions). The
      fMRI analysis of the recognition data was restricted to correct items only and a
      random effects model was used. RESULTS: At the behavioral level, both groups
      performed equally well on item recognition, whereas people with schizophrenia
      demonstrated lower performance on associative recognition relative to the control
      group. At the brain level, the comparison between associative and item encoding
      revealed greater activity in the control group in the left prefrontal cortex and
      cingulate gyrus relative to the schizophrenia group. During recognition, greater
      left dorsolateral prefrontal and right inferior prefrontal activations were
      observed in the control group relative to the schizophrenia group. CONCLUSION:
      This fMRI study implicates the prefrontal cortex among other brain regions as the
      basis for the selective associative memory encoding and recognition deficit seen
      in schizophrenia.

PMID- 16814266
TI  - Recovery after short-term bilirubin exposure in human NT2-N neurons.
AB  - We used human NT2-N neurons to investigate delayed effects of short-term exposure
      to unconjugated bilirubin (UCB). Cell viability was evaluated with MTT reduction
      assays and nuclear morphology. A 6-h exposure to 1, 5, or 25 microM UCB and serum
      deprivation (SED) significantly diminished MTT reduction. 96 h after rescue of
      neurons with removal of UCB and re-incubation in the original serum-containing
      medium, delayed effects were evident as recovery (1 microM UCB), intermediate
      cell death (5 microM UCB), or near complete cell death (25 microM UCB). The
      impact of 6 h of SED alone appeared to be modest in rescued neurons. In this
      model, co-treatment with the specific caspase-3 inhibitor, zDEVD.FMK (100
      microM), or the pancaspase inhibitor zVAD.FMK (100 microM) did not improve
      viability in rescued neurons exposed to 5 microM UCB, while treatment with the
      NMDA receptor antagonist MK-801 (1 microM) enhanced the number of undamaged
      nuclei (86 +/- 14% versus 50 +/- 12%, P = 0.001). MK-801 had, however, no impact
      on MTT reduction. In a different model with a 102-h continuous exposure to UCB
      and SED, we found a significant additional toxic impact of serum deprivation.
      Separate experiments suggested that this was a result of late caspase-mediated
      toxicity. We conclude that UCB-mediated effects may be reversible in this model.
      Blockade of excitotoxic mechanisms, but not caspase activity may prevent delayed
      cell death.

PMID- 16814267
TI  - Mice without transcription factor KLF7 provide new insight into olfactory bulb
      development.
AB  - Recent genetic studies have excluded that peripheral innervation plays a
      substantial role in the initial outgrowth of the olfactory bulb. Mice without
      Kruppel-like factor 7 activity die at birth and display hypoplastic olfactory
      bulbs which lack peripheral innervation. Here, we report that incomplete
      penetrance of the mutation is responsible for partial bulb innervation in a small
      fraction of Klf7 null mice. Analysis of the partially innervated bulbs of mutant
      embryos, newborns and adult mice revealed an obligatory correlation with local
      restoration of laminar architecture, neuronal cell differentiation and neuronal
      activity. The degree of normal OB maturation in Klf7-/- OBs was proportional to
      the degree of peripheral innervation. These findings therefore indicate that
      peripheral innervation contributes to bulb maturation late in development by
      promoting cell morphogenesis and differentiation.

PMID- 16814268
TI  - The distribution of expression of doublecortin (DCX) mRNA and protein in the
      zebra finch brain.
AB  - Using in situ hybridization, we measured the distribution of expression of
      doublecortin (DCX), a microtubule-associated protein, in zebra finch adult and
      nestling (P9-11) brains. In adult brain, DCX mRNA was detected mainly in the
      mesopallium (M), medial striatum (MSt), septum, Area X, diencephalon,
      telencephalic subventricular zone (SVZ), and Purkinje cells in the cerebellum.
      The expression at posthatch day 9 (P9) was heavy in almost the entire
      telencephalon and showed heavier expression in SVZ and song regions such as the
      high vocal center (HVC) and the robust nucleus of arcopallium (RA). Outside of
      the telencephalon at P9, we found distinct label in nucleus ovoidalis (OV),
      nucleus spiriformis lateralis (SpL), and nucleus subpretectalis (SP) in the
      midbrain, almost the entire diencephalon including nucleus dorsomedialis
      posterior thalami (DMP), stratum griseum et fibrosum superficiale (SGF) in optic
      tectum, and Purkinje cells in cerebellum. Most of the heavily labeled areas by in
      situ hybridization overlapped with immunohistochemical staining for DCX,
      indicating that DCX mRNA is probably translated into protein in those regions. No
      sex difference was found in DCX expression at P9 or in the adult except that Area
      X was labeled only in the adult male. The intensity of expression in the adult
      was significantly lower than that at P9, which suggests a particular role for DCX
      in early song bird brain development. If DCX is predominantly expressed in
      migrating neurons, as suggested from studies in mammals, the present results
      offer no evidence for a sex difference in neuronal migration.

PMID- 16814269
TI  - Reduced Nuclear Factor kappa B activation in dentate gyrus after active avoidance
      training.
AB  - Nuclear Factor kappa B (NF-kappaB) is a transcription factor associated with
      neuroplasticity and neuronal survival during injury. Although NF-kappaB has been
      proven to be involved in various processes of repair, there is also evidence that
      NF-kappaB is associated with learning and memory formation. Our laboratory has
      previously observed that mice lacking the NF-kappaB p50 subunit are not
      proficient in learning tasks associated with active avoidance training, an
      effective learning paradigm. The purpose of this study is to identify changes in
      NF-kappaB levels after active avoidance training using kappaB-dependent lacZ
      transgenic mice. Levels of NF-kappaB activity were detected immunohistochemically
      after active avoidance training in brain regions associated with learning and
      memory. NF-kappaB activity in trained mice was significantly decreased in the
      dentate gyrus, but no significant changes were found in other brain regions of
      trained mice compared to untrained mice. The number of p50-containing neurons was
      counted in the dentate gyrus and a significant increase was discovered in the
      trained mice relative to untrained mice. The decrease of NF-kappaB-containing
      neurons in the dentate gyrus coincides with elevated levels of activated p50
      neurons and may be caused by the ability of p50 homodimers to inhibit NF-kappaB
      transactivation. These results indicate that increased p50 expression down
      regulates NF-kappaB activity in the dentate gyrus after exposure to unconditioned
      stimulus. Therefore, a reduction of NF-kappaB activation and its target genes
      appears to be a necessary event for early stages of learning and memory
      consolidation associated with active avoidance training.

PMID- 16814270
TI  - Mimotope vaccination for epitope-specific induction of anti-CD20 antibodies.
AB  - CD20 is expressed strictly by B-cells and is ubiquitously expressed at high
      surface densities of malignant human B-cells. This suggests that CD20 may be a
      tumor target for immunotherapy of B-cell lymphomas. Rituximab, a chimeric
      monoclonal antibody directed against CD20, has been demonstrated to be an
      effective treatment for non-Hodgkin's lymphoma (NHL) and some autoimmune
      diseases. In the current study, we used the phage display technique to generate
      mimotopes that complemented the screening Ab Rituximab. A total of seven
      candidate mimotopes were isolated from a 12-mer peptide library from which one
      mimotope was conjugated to keyhole limpet hemocyanin (KLH) or tetanus toxoid
      (TT). The immunogenicity of the two vaccines generated was examined in BALB/c
      mice. Sera from the vaccinated mice demonstrated high-titer specific antibodies
      to the mimotope conjugates. Antibody binding to native CD20 and Ab-mediated
      cytotoxicity (CDC, complement-dependent cytotoxicity) were also analyzed. Our
      data suggest that a Rituximab mimotope may be a useful tool for the construction
      of a functional vaccine to treat B-cell malignancy as well as some CD20 related
      autoimmune disorders.

PMID- 16814271
TI  - Induction of alpha-fetoprotein-specific CD4- and CD8-mediated T-cell response
      using RNA-transfected dendritic cells.
AB  - alpha-Fetoprotein (AFP) may be a possible target for a hepatocellular carcinoma
      (HCC)-specific vaccination. But some studies have demonstrated that dendritic
      cells (DCs) treated with AFP become dysfunctional. So in this study, we try to
      transfect AFP mRNA into DCs and observe the ability of DCs to induce AFP-specific
      CD4(+) and CD8(+) T cells. We hope that AFP can be processed and presented by DCs
      directly, rather than released to the cultures. So there will be no AFP negative
      effect on the function of DCs. In the study, immature DCs generated from
      peripheral blood mononuclear cells (PBMCs) of HLA-A2(+) HCC patients were
      transfected with AFP mRNA. Then the transfected, matured DCs were used to
      stimulate autologous T cells. The results showed that the expressions of membrane
      molecules of DCs after transfection were increased dramatically, and interleukin
      12 (IL-12) p70 release in the supernatant was elevated significantly. There was
      only a minority of AFP release in the supernatants of transfected DCs. CTLs
      induced by the transfected DCs recognized HLA-matched AFP positive HepG2 cell
      line specifically and the AFP-specific proliferative T-cell responses could also
      be induced. These findings indicate that this AFP mRNA transfection strategy
      could generate fully functional DCs, which could induce specific T cells to
      recognize AFP(+) HCC cells.

PMID- 16814272
TI  - No significant difference between Uygur and Han Chinese populations for genetic
      polymorphism of GSTP1.

PMID- 16814273
TI  - Antigen-specific free immunoglobulin light-chain antibodies: could it be a new
      diagnostic marker for patients with allergy?
AB  - OBJECTIVES: Human free immunoglobulin light chains (FLCs) have long been
      considered as nonmeaningful spillover remnants from the process of immunoglobulin
      production; however, recent findings suggest that the antibody activity of FLCs
      may be involved in the pathology of allergic responses. We therefore assessed the
      antigen-binding ability of FLCs to evaluate their usefulness as diagnostic
      markers for patients with allergy. DESIGN AND METHODS: FLCs were separated from
      the serum samples of patients seropositive against cedar pollen and mice
      immunized with bovine serum albumin and 1-fluoro-2,4-dinitrobenzene by
      ultrafiltration and protein G absorption. A sensitive immunoassay confirmed the
      absence of any IgG in the separated FLC fractions from the human serum samples.
      RESULTS: Solid-phase immunoassay for cedar pollen showed that none of the human
      serum samples possessed any antibody activity against the antigen after the
      removal of whole immunoglobulins. Furthermore, while the immunized mice also
      showed high antibody titers against the antigens, but the serum specimens showed
      no residual antibody activity against the antigens after the FLCs were separated
      from the whole immunoglobulins. CONCLUSIONS: The results of the present study
      suggested that the FLC fractions may possess little or no antigen-binding
      activity, and that therefore, they may not serve as useful diagnostic markers in
      patients with allergy.

PMID- 16814274
TI  - Concept empiricism: a methodological critique.
AB  - Thanks to Barsalou's, Damasio's, Glenberg's, Prinz' and others' work, neo
      empiricism is gaining a deserved recognition in the psychology and philosophy of
      concepts. I argue, however, that neo-empiricists have underestimated the
      difficulty of providing evidence against the amodal approach to concepts and
      higher cognition. I highlight three key problems: the difficulty of sorting out
      amodal predictions from neo-empiricist predictions, the difficulty of finding
      experimental tasks that are not best solved by imagery and the difficulty of
      generalizing findings concerning a given cognitive process in a given context to
      other cognitive processes or other contexts. Finally, solutions to these three
      problems are considered.

PMID- 16814275
TI  - Unconscious priming according to multiple S-R rules.
AB  - The present study investigated if unconscious primes can be processed according
      to different stimulus-response (S-R) rules simultaneously. Participants performed
      two different S-R rules, such as judging a digit as smaller or larger than five
      and judging a letter as vowel or consonant. These S-R rules were administered in
      random order and announced by a previously presented cue. Each target stimulus
      was preceded by subliminal primes which afforded a different or an identical
      response according to either the currently irrelevant or currently relevant S-R
      rule. In three experiments, we consistently found priming effects according to
      currently irrelevant S-R rules, even when primes for the relevant and irrelevant
      S-R rules were presented simultaneously. Thus, unconscious stimuli have the power
      to activate responses according to currently required and currently not required
      S-R rules concurrently. The results are in line with response activation accounts
      of subliminal priming and suggest that at least two routes may gain access on
      response processes simultaneously.

PMID- 16814276
TI  - Decapentaplegic head capsule mutations disrupt novel peripodial expression
      controlling the morphogenesis of the Drosophila ventral head.
AB  - Drosophila adult structures derive from imaginal discs, which are sacs with
      apposed epithelial sheets, the disc proper (DP) and the peripodial epithelium
      (PE). The Drosophila TGF-beta family member decapentaplegic (dpp) contributes to
      the development of adult structures through expression in all imaginal discs,
      driven by enhancers from the 3' cis-regulatory region of the gene. In the
      eye/antennal disc, there is 3' directed dpp expression in both the DP and PE
      associated with cell proliferation and eye formation. Here, we analyze a new
      class of dpp cis-regulatory mutations, which specifically disrupt a previously
      unknown region of dpp expression, controlled by enhancers in the 5' regulatory
      region of the gene and limited to the PE of eye/antennal discs. These are the
      first described Drosophila mutations that act by solely disrupting PE gene
      expression. The mutants display defects in the ventral adult head and alter
      peripodial but not DP expression of known dpp targets. However, apoptosis is
      observed in the underlying DP, suggesting that this peripodial dpp signaling
      source supports cell survival in the DP.

PMID- 16814277
TI  - Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia,
      dyslipidemia and oxidative stress in rats.
AB  - This study examined whether sucrose-rich diet (SRD)-induced hyperglycaemia,
      dyslipidemia and oxidative stress may be inhibited by N-acetylcysteine (C(5)H(9)
      NO(3)S), an organosulfur from Allium plants. Male Wistar 40 rats were divided
      into four groups (n=10): (C) given standard chow and water; (N) receiving
      standard chow and 2 mg/l N-acetylcysteine in its drinking water; (SRD) given
      standard chow and 30% sucrose in its drinking water; and (SRD-N) receiving
      standard chow, 30% sucrose and N-acetylcysteine in its drinking water. After 30
      days of treatment, SRD rats had obesity with increased abdominal circumference,
      hyperglycaemia, dyslipidemia and hepatic triacylglycerol accumulation. These
      adverse effects were associated with oxidative stress and depressed lipid
      degradation in hepatic tissue. The SRD adverse effects were not observed in SDR-N
      rats. N-Acetylcysteine reduced the oxidative stress, enhancing glutathione
      peroxidase activity, and normalizing lipid hydroperoxyde, reduced glutathione and
      superoxide dismutase in hepatic tissue of SRD-N rats. The beta-hydroxyacyl
      coenzyme-A dehydrogenase and citrate-synthase activities were increased in SRD-N
      rats, indicating enhanced lipid degradation in hepatic tissue as compared to SRD.
      SRD-N rats had reduced serum oxidative stress and diminished glucose,
      triacylglycerol, very-low-density lipoprotein (VLDL), oxidized low-density
      lipoprotein (ox-LDL) and cholesterol/high-density lipoprotein (HDL) ratio in
      relation to SRD. In conclusion, NAC offers promising therapeutic values in
      prevention of dyslipidemic profile and alleviation of hyperglycaemia in high
      sucrose intake condition by improving antioxidant defences. N-Acetylcysteine had
      also effects preventing metabolic shifting in hepatic tissue, thus enhancing fat
      degradation and reducing body weight gain in conditions of excess sucrose intake.
      The application of this agent in food system via exogenous addition may be
      feasible and beneficial for antioxidant protection.

PMID- 16814278
TI  - Endothelin ETA receptor blockade potentiates morphine analgesia but does not
      affect gastrointestinal transit in mice.
AB  - Development of analgesic tolerance and constipation remain a major clinical
      concern during long-term administration of morphine in pain management. Central
      endothelin mechanisms are involved in morphine analgesia and tolerance. The
      present study was conducted to investigate the effect of intracerebroventricular
      (i.c.v.) and peripheral administration of endothelin ET(A) receptor antagonist,
      BMS182874, and endothelin ET(B) receptor agonist, IRL1620, on morphine analgesia
      and changes in gastrointestinal transit in male Swiss Webster mice. Results
      indicate that morphine (6 mg/kg, s.c.) produced a significant increase in tail
      flick latency compared to control group. Pretreatment with BMS182874 (50 microg,
      i.c.v.) significantly enhanced morphine-induced analgesia, while IRL1620 (30
      microg, i.c.v.) pretreatment did not affect tail-flick latency values. Changes in
      gastrointestinal transit were measured by percent of distance traveled by
      charcoal in the small intestine of gastrointestinal tract. Percent distance
      traveled in morphine (6 mg/kg, s.c.) treated mice (48.45+/-5.65%) was
      significantly lower (P<0.05) compared to control group (85.07+/-1.82%).
      Administration of BMS182874 centrally (50 mug, i.c.v.) or peripherally (10 mg/kg,
      i.p.) did not affect morphine-induced inhibition of gastrointestinal transit.
      Pretreatment with IRL1620 (30 microg, i.c.v., or 10 mg/kg, i.v.) also did not
      affect morphine-induced inhibition of gastrointestinal transit. This study
      demonstrates that endothelin ET(A) receptor antagonists delivered to the CNS
      enhance morphine analgesia without affecting gastrointestinal transit.

PMID- 16814279
TI  - Nimesulide-induced antipyresis in rats involves both cyclooxygenase-dependent and
      independent mechanisms.
AB  - This study evaluates the antipyretic activity of nimesulide, a cyclooxygenase
      (COX-2) selective inhibitor in rats. The effects of nimesulide on
      lipopolysaccharide (LPS)-induced cerebrospinal prostaglandin E(2) (PGE(2)) and
      prostaglandin F(2alpha) (PGF(2alpha)) and on plasma tumor necrosis factor-alpha
      (TNF-alpha) levels were also evaluated. Male Wistar rats received an i.p.
      injection of LPS, or i.c.v. injections of interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), TNF-alpha, macrophage inflammatory protein-1alpha (MIP
      1alpha), arachidonic acid, PGE(2), PGF(2alpha), corticotrophin-releasing factor
      (CRF) or endothelin-1 (ET-1). Nimesulide or indomethacin administered i.p 30 min
      prior LPS, IL-1beta, IL-6, TNF-alpha or arachidonic acid reduced the febrile
      response and PGE(2) or PGF(2alpha) levels in LPS-febrile rats but did not modify
      PGE(2)-induced fever. Nimesulide, but not indomethacin, reduced the fever induced
      by MIP-1alpha, PGF(2alpha), CRF or ET-1. Plasma TNF-alpha levels in LPS-treated
      rats were also reduced by nimesulide. These findings confirm that the antipyretic
      effect of nimesulide differs from the antipyretic scenario with the non-selective
      cyclooxygenase blocker indomethacin. Additional mechanisms, including inhibition
      of increased plasma TNF-alpha, may contribute to its antipyretic activity in
      rats.

PMID- 16814280
TI  - Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced
      hyperlipidemic cardiomyopathy.
AB  - Cyclophosphamide is a potent alkylating agent used in cancer chemotherapy and
      immunosuppression. The present study is aimed at evaluating the role of a potent
      antioxidant lipoic acid in cyclophosphamide induced hyperlipidemic
      cardiomyopathy. Adult male Wistar rats were divided into four treatment groups.
      Two groups received single intraperitoneal injection of cyclophosphamide (200
      mg/kg body weight) to induce cardiotoxicity, one of these groups received lipoic
      acid treatment (25 mg/kg body weight, orally for 10 days). A vehicle treated
      control group and a lipoic acid drug control were also included. Cyclophosphamide
      administration resulted in abnormal elevation of serum lipids. Similarly in the
      cardiac tissue, the levels of free cholesterol, esterified cholesterol,
      triglycerides were increased significantly (P<0.05) while the levels of
      phospholipids and free fatty acids were reduced significantly unlike serum
      (P<0.05). Serum Low Density Lipoprotein (LDL) and Very Low Density Lipoprotein
      (VLDL) cholesterol increased significantly (P<0.05) while High Density
      Lipoprotein (HDL) cholesterol (P<0.05) decreased significantly when compared to
      controls. These changes corroborated with the abnormal distortion in the
      activities of lipid metabolizing enzymes in cyclophosphamide treated group.
      Supplementation of lipoic acid reverted these abnormalities in the lipid levels
      and activities of lipid metabolizing enzymes to near normalcy after
      cyclophosphamide administration.

PMID- 16814281
TI  - Cytoplasmic translocation of Olig2 in adult glial progenitors marks the
      generation of reactive astrocytes following autoimmune inflammation.
AB  - The injury response in the brain involves complex interplay between neural and
      immune components. Following inflammatory insults to the adult CNS, formation of
      an astroglial scar often impedes functional repair. Glial progenitor cells
      expressing the nuclear transcription factor Olig2 possibly generate astrocytes in
      response to various types of injuries; however, the mechanisms underlying this
      differentiation are unclear. In a model of immune-mediated injury (MOG(35-55)
      experimental autoimmune encephalomyelitis), we show that the conversion from
      progenitor to reactive astrocyte is marked by the translocation of Olig2 into the
      cytoplasm. Evidence of this process is found for months after disease initiation
      in the absence of new inflammatory infiltrates. A proportion of cells with
      cytoplasmic Olig2 was found to express NG2 or Nkx2.2, but only Nkx2.2 was
      occasionally retained by GFAP+ cells. We further show that differentiation to
      astrocytes is induced in glial progenitors in vitro through exposure to the pro
      inflammatory cytokine IFN-gamma, but not to TNF-alpha. Together, these data
      ascribe a pivotal role to Olig2+ glial precursor cells in the adult CNS, linking
      autoimmune inflammation and glial scar formation.

PMID- 16814282
TI  - Actions at sites other than D(3) receptors mediate the effects of BP897 on l-DOPA
      induced hyperactivity in monoamine-depleted rats.
AB  - The role of D(3) receptors in the antiparkinsonian actions of l-DOPA and l-DOPA
      induced dyskinesia (LID) remains unclear. The D(3) receptor partial agonist BP897
      attenuates LID in primates without affecting the antiparkinsonian actions of l
      DOPA, suggesting that "normalization" of D(3) activity is antidyskinetic [Bezard,
      E., Ferry, S., Mach, U., Stark, H., Leriche, L., Boraud, T., Gross, C., and
      Sokoloff, P., 2003. Attenuation of levodopa-induced dyskinesia by normalizing
      dopamine D(3) receptor function. Nat. Med. 9, 762-767]. However, subsequent
      studies have questioned these findings [Hsu, A., Togasaki, D.M., Bezard, E.,
      Sokoloff, P., Langston, J.W., Di Monte, D.A., and Quik, M., 2004. Effect of the
      D(3) dopamine receptor partial agonist BP897 [N-[4-(4-(2
      methoxyphenyl)piperazinyl)butyl]-2-naphthamide] on l-3,4-dihydroxyphenylalanine
      induced dyskinesias and parkinsonism in squirrel monkeys. J. Pharmacol. Exp.
      Ther. 311, 770-777]. The D(3) receptor antagonist S33084 is not antidyskinetic
      yet enhances the antiparkinsonian actions of l-DOPA, suggesting that stimulation
      of D(3) receptors is not involved in LID. Here, we address the possibility that
      in vivo BP897 acts via mechanisms in addition to attenuation of D(3) signaling. l
      DOPA (125 mg/kg) elicits hyperkinesia in reserpine-treated rats, the vertical
      component of which (rearing) is attenuated by agents with antidyskinetic actions
      in MPTP-lesioned primates and Parkinson's disease (PD) [Johnston, T.H., Lee, J.,
      Gomez-Ramirez, J., Fox, S.H., and Brotchie, J.M., 2005. A simple rodent assay for
      the in vivo identification of agents with potential to reduce levodopa-induced
      dyskinesia in Parkinson's disease. Exp. Neurol. 191, 243-250]. BP897 (0.1, 0.3,
      1.0 and 3 mg/kg) reduced l-DOPA-induced rearing by 0%, 44%, 86% and 57%
      respectively. In contrast, S33084 had no effect on l-DOPA-induced rearing (0.1
      mg/kg, 115%; 0.3 mg/kg, 94%, 1 mg/kg, 134%; 3 mg/kg, 100%, of vehicle, all P >
      0.05). Furthermore, S33084 failed to antagonize the effects of BP897 on l-DOPA
      induced rearing. The influence of BP897 on l-DOPA-induced rearing was, however,
      mimicked by the selective D(2) antagonist L741,626. Finally, BP897 attenuated l
      DOPA-induced horizontal activity, an action attenuated by S33084 and mimicked by
      L741,626. Thus, while BP897 may reduce LID, we raise the possibility that
      receptors other than D(3) receptors might be involved in this action.

PMID- 16814283
TI  - Disentangling the contribution of the paretic and non-paretic ankle to balance
      control in stroke patients.
AB  - During stroke recovery, restoration of the paretic ankle and compensation in the
      non-paretic ankle may contribute to improved balance maintenance. We examine a
      new approach to disentangle these recovery mechanisms by objectively quantifying
      the contribution of each ankle to balance maintenance. Eight chronic hemiparetic
      patients were included. Balance responses were elicited by continuous random
      platform movements. We measured body sway and ground reaction forces below each
      foot to calculate corrective ankle torques in each leg. These measurements
      yielded the Frequency Response Function (FRF) of the stabilizing mechanisms,
      which expresses the amount and timing of the generated corrective torque in
      response to sway at the specified frequencies. The FRFs were used to calculate
      the relative contribution of the paretic and non-paretic ankle to the total
      amount of generated corrective torque to correct sway. All patients showed a
      clear asymmetry in the balance contribution in favor of the non-paretic ankle.
      Paretic balance contribution was significantly smaller than the contribution of
      the paretic leg to weight bearing, and did not show a clear relation with the
      contribution to weight bearing. In contrast, a group of healthy subjects
      instructed to distribute their weight asymmetrically showed a one-on-one relation
      between the contribution to weight bearing and to balance. We conclude that the
      presented approach objectively quantifies the contribution of each ankle to
      balance maintenance. Application of this method in longitudinal surveys of
      balance rehabilitation makes it possible to disentangle the different recovery
      mechanisms. Such insights will be critical for the development and evaluation of
      rehabilitation strategies.

PMID- 16814284
TI  - Relationship of calpain-mediated proteolysis to the expression of axonal and
      synaptic plasticity markers following traumatic brain injury in mice.
AB  - The role of neuronal plasticity and repair on the final functional outcome
      following traumatic brain injury (TBI) remains poorly understood. Moreover, the
      relationship of the magnitude of post-traumatic secondary injury and
      neurodegeneration to the potential for neuronal repair has not been explored. To
      address these questions, we employed Western immunoblotting techniques to examine
      how injury severity affects the spatial and temporal expression of markers of
      axonal growth (growth-associated protein GAP-43) and synaptogenesis (pre-synaptic
      vesicular protein synaptophysin) following either moderate (0.5 mm, 3.5 M/s) or
      severe (1.0 mm, 3.5 M/s) lateral controlled cortical impact traumatic brain
      injury (CCI-TBI) in young adult male CF-1 mice. Moderate CCI increased GAP-43
      levels at 24 and 48 h post-insult in the ipsilateral hippocampus relative to
      sham, non-injured animals. This increase in axonal plasticity occurred prior to
      maximal hippocampal neurodegeneration, as revealed by de Olmos silver staining,
      at 72 h. However, moderate CCI-TBI did not elevate GAP-43 expression in the
      ipsilateral cortex where neurodegeneration was extensive by 6 h post-TBI. In
      contrast to moderate injury, severe CCI-TBI failed to increase hippocampal GAP-43
      levels and instead resulted in depressed GAP-43 expression in the ipsilateral
      hippocampus and cortex at 48 h post-insult. In regards to injury-induced changes
      in synaptogenesis, we found that moderate CCI-TBI elevated synaptophysin levels
      in the ipsilateral hippocampus at 24, 48, 72 h and 21 days, but this effect was
      not present after severe injury. Together, these data highlights the adult
      brain's ability for axonal and synaptic plasticity following a focal cortical
      injury, but that severe injuries may diminish these endogenous repair mechanisms.
      The differential effects of moderate versus severe TBI on the post-traumatic
      plasticity response may be related to the calpain-mediated proteolytic activity
      occurring after a severe injury preventing increased expression of proteins
      required for plasticity. Supporting this hypothesis is the fact that GAP-43 is a
      substrate for calpain along with our data demonstrating that calpain-mediated
      degradation of the cytoskeletal protein, alpha-spectrin, is approximately 10
      times greater in ipsilateral hippocampal tissue following severe compared to
      moderate CCI-TBI. Thus, TBI severity has a differential effect on the injury
      induced neurorestorative response with calpain activation being one putative
      factor contributing to neuroregenerative failure following severe CCI-TBI. If
      true, then calpain inhibition may lead to both neuroprotective effects and an
      enhancement of neuronal plasticity/repair mechanisms post-TBI.

PMID- 16814285
TI  - Plasmodium berghei: in vitro and in vivo activity of dequalinium.
AB  - Bisquinoline compounds have exhibited remarkable activity in vitro and in vivo
      against Plasmodium parasites by inhibition of heme detoxification. We have tested
      the ability of dequalinium 1,1'-(1,10-decanediyl)bis(4-amino-2-methylquinoline),
      a known antimicrobial agent, to inhibit beta-hematin synthesis using a non
      emzymatic colorimetric assay and globin proteolysis by electrophoretic analysis
      (SDS-PAGE-15%). Dequalinium was able to inhibit both processes in vitro with
      close correlation to a murine malaria model, reducing parasitemia levels,
      prolonging the survival time post-infection and curing 40% of infected mice using
      a combination therapy with a loading dose of chloroquine. These results confirm
      that dequalinium is a promising lead for antimalarial drug development.

PMID- 16814286
TI  - Paragonimus westermani: biochemical and immunological characterizations of
      paramyosin.
AB  - Paramyosin of the helminth parasite is a muscle protein that plays
      multifunctional roles in host-parasite relationships. In this study, we have
      cloned a gene encoding Paragonimus westermani paramyosin (PwPmy) and
      characterized biochemical and immunological properties of the recombinant
      protein. The recombinant PwPmy (rPwPmy) was shown to bind both human
      immunoglobulin G (IgG) and collagen. The protein was constitutively expressed in
      various developmental stages of the parasite and its expression level increased
      progressively as the parasite matured. Immunohistological analysis revealed that
      PwPmy was mainly localized in subtegumental muscle, tegument and cells
      surrounding the oral sucker, intestine, and ovary of the parasite. Sera from
      patients with paragonimiasis showed antibody reactivity against rPwPmy, and IgG1
      and IgG4 were predominant. Immunization of mice with rPwPmy also induced high IgG
      responses. Biochemical and immunological characterization of PwPmy may provide
      valuable information for the further study to develop a vaccine or a
      chemotherapeutic agent for paragonimiasis.

PMID- 16814287
TI  - Presenilin-1 is an unprimed glycogen synthase kinase-3beta substrate.
AB  - Previously we described presenilin-1 (PS1) as a GSK-3beta substrate
      [Kirschenbaum, F., Hsu, S.C., Cordell, B. and McCarthy, J.V. (2001) Substitution
      of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1
      separates presenilin function from beta-catenin signalling. J. Biol. Chem. 276,
      7366-7375; Kirschenbaum, F., Hsu, S.C., Cordell, B. and McCarthy, J.V. (2001)
      Glycogen synthase kinase-3beta regulates presenilin 1 C-terminal fragment levels.
      J. Biol. Chem. 276, 30701-30707], though it has not been determined whether PS1
      is a primed or unprimed GSK-3beta substrate. A means of separating GSK-3beta
      activity toward primed and unprimed substrates was identified in the GSK-3beta
      R96A phosphate binding pocket mutant [Frame, S., Cohen, P. and Biondi, R.M.
      (2001) A common phosphate binding site explains the unique substrate specificity
      of GSK3 and its inactivation by phosphorylation. Mol. Cell 7, 1321-1327], which
      is unable to phosphorylate primed but retains the ability to phosphorylate
      unprimed GSK-3beta substrates. By using wild type GSK-3beta, GSK-3beta-R96A, and
      a pharmacological modulator of GSK-3beta activity, we demonstrate that PS1 is an
      unprimed GSK-3beta substrate. These findings have important implications for
      regulation of PS1 function and the pathogenesis of Alzheimer's disease.

PMID- 16814288
TI  - Enhancement of sapovirus recombinant capsid protein expression in insect cells.
AB  - Human sapovirus (SaV) is uncultivable, but expression of the recombinant capsid
      protein (rVP1) in insect cells results in the formation of virus-like particles
      (VLPs) that are morphologically similar to the native viruses. However, the SaV
      rVP1 expression levels are considerably low. We have found that inclusions of
      short foreign nucleotide sequences inserted directly upstream from the predicted
      rVP1 AUG start codon lead to increased yield of VLPs. This method allowed us to
      express a SaV rVP1, which could not have been expressed to measurable or
      practical levels otherwise.

PMID- 16814289
TI  - Estradiol production during controlled ovarian hyperstimulation correlates with
      treatment outcome in women undergoing in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To study the value of E(2) production during controlled ovarian
      hyperstimulation (COH) in predicting IVF-ET outcome. DESIGN: Historical cohort.
      SETTING: Academic infertility center. PATIENT(S): A cohort of 270 patients who
      completed 324 consecutive IVF-ET treatment cycles. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Area under the curve for E(2) levels (AUC-E(2)) from the
      first day of COH until the day of hCG administration was calculated and cycles
      grouped into low, average, and high AUC-E(2) groups. Clinical pregnancy rates per
      cycle were compared among the three groups, and correlations with AUC-E(2) values
      were calculated for all patients and after sub-grouping according to age, COH
      protocol and infertility diagnosis. RESULT(S): Cycles with low and high AUC-E(2)
      values had significantly lower pregnancy rates particularly in patients 35 years
      or older. There was a positive correlation between AUC-E(2) and pregnancy rates
      up to a certain AUC-E(2) level above which a negative correlation was found. The
      turning point between positive and negative correlations occurred at a
      significantly lower AUC-E(2) level in patients 35 years or older. CONCLUSIONS:
      Estradiol production during COH correlates with IVF-ET outcome. Women >35 years
      of age seem more vulnerable to high E(2) levels.

PMID- 16814290
TI  - Association between sperm autoantibodies and enhanced embryo implantation rates
      during in vitro fertilization.
AB  - Previous investigations have demonstrated the propensity of strong IgA-class
      sperm autoantibodies to impede fertilization. However, because there has not been
      a general consensus on this issue, the aim of this retrospective analysis was to
      focus on the effects of different levels of IgA-class antibodies on each stage of
      the IVF procedure. This study has confirmed that high level IgA class antibodies
      significantly reduce fertilization rates but, unexpectedly, also has shown a very
      significant improvement in embryo implantation rates in patients with weak to
      moderate antibody levels. Interlaboratory prospective collaborative studies are
      being planned to test this preliminary observation more stringently.

PMID- 16814291
TI  - Recovery of human sperm motility and ability to interact with the human zona
      pellucida after more than 28 years of storage in liquid nitrogen.
AB  - Six donor semen samples were evaluated after 28 years cryopreservation in liquid
      nitrogen. The results showed that the samples retained good postthaw motility
      recovery and normal levels of binding to the human zona pellucida and that four
      of the five samples tested also gave normal levels of zona-induced acrosome
      reaction. In conclusion, human sperm can survive very long-term storage, which is
      pertinent information for clinicians referring boys and young men for sperm
      banking before chemotherapy.

PMID- 16814292
TI  - Estrogen and exercise may be related to body fat distribution and leptin in young
      women.
AB  - OBJECTIVE: To evaluate the effects of estrogen deficiency and exercise on body
      composition and leptin in young women. DESIGN: Cross-sectional clinical study.
      SETTING: Volunteers in an academic research environment. PATIENT(S): Three age-
      and body mass index-matched groups: normal-weight women with exercise-associated
      amenorrhea, regularly menstruating exercising control women, and regularly
      menstruating normally active control women. INTERVENTION(S): Collection of blood
      samples and measurement of body fat and regional fat distribution by dual-energy
      x-ray absorptiometry. MAIN OUTCOME MEASURE(S): Central fat accumulation (i.e.,
      ratio of trunk to extremity fat) and serum concentrations of E(2) and leptin.
      RESULT(S): In both regularly menstruating control groups, but not in the
      amenorrheic women, there was a negative correlation between the serum E(2)
      concentrations and the trunk-to-extremity fat ratio (r = -0.4), independent of
      age, exercise, body fat, and serum T concentrations. In all women, E(2)
      concentrations were positively and exercise inversely correlated to leptin
      concentrations, independent of body fat. CONCLUSION(S): Estradiol level is
      inversely associated with central fat accumulation only in women with regular
      menstrual cycles. In all young premenopausal subjects, estrogen secretion
      influences leptin concentrations independently of body fat.

PMID- 16814293
TI  - CT imaging of wet specimens from a pathology museum: How to build a "virtual
      museum" for radiopathological correlation teaching.
AB  - X-rays and CT have been used to examine specimens such as human remains, mummies
      and formalin-fixed specimens. However, CT has not been used to study formalin
      fixed wet specimens within their containers. The purpose of our study is firstly
      to demonstrate the role of CT as a non-destructive imaging method for the study
      of wet pathological specimens and secondly to use the CT data as a method for
      teaching pathological and radiological correlation. CT scanning of 31
      musculoskeletal specimens from a pathology museum was carried out. Images were
      reconstructed using both soft-tissue and bone algorithms. Further processing of
      the data produced coronal and sagittal reformats of each specimen. The container
      and storage solution were manually removed using Volume Viewer Voxtool software
      to produce a 3D reconstruction of each specimen. Photographs of each specimen
      (container and close-up) were displayed alongside selected coronal, sagittal, 3D
      reconstructions and cine sequences in a specially designed computer program. CT
      is a non-destructive imaging modality for building didactic materials from wet
      specimens in a Pathology Museum, for teaching radiological and pathological
      correlation.

PMID- 16814294
TI  - Contrasting patterns in the small-scale heterogeneity of human helminth
      infections in urban and rural environments in Brazil.
AB  - Marked heterogeneity exists in the patterns of parasitic infection between
      individuals, households and communities. Analysis of parasite distributions
      within populations is complicated by the fact that parasite distributions are
      highly aggregated and few studies have explicitly incorporated this distribution
      when investigating small-scale spatial heterogeneities. This study aimed to
      quantify the small-scale (within- and between-household) heterogeneity of
      helminth infection in an area of Minas Gerais State, Brazil, with rural and urban
      sectors. Parasitological data from a cross-sectional survey of 1,249 individuals
      aged 0-86 years from 242 households were analysed. Within-household clustering of
      infection was assessed using random effect logistic regression models and between
      household spatial heterogeneity was assessed using a Bayesian negative binomial
      spatial model. The overall prevalence of hookworm (Necator americanus) was 66.9%,
      the prevalence of Schistosoma mansoni was 44.9% and the prevalence of Ascaris
      lumbricoides was 48.8%. Statistical analysis indicated significant (within)
      household and (between household) spatial clustering of hookworm in both rural
      and urban areas and of S. mansoni in rural areas. There was no evidence of either
      household or spatial clustering of S. mansoni in urban areas. The spatial
      correlation of S. mansoni was estimated to reduce by half over a distance of 700
      m in the rural area. Rural hookworm had a much smaller half-distance (28 m) and
      urban hookworm showed an even smaller half-distance (12 m). We suggest that such
      species-specific differences in patterns of infection by environment are
      primarily due to variation in exposure and parasite life cycle, although host
      genetic factors cannot be ruled out.

PMID- 16814295
TI  - Statins inhibit NK cell cytotoxicity by membrane raft depletion rather than
      inhibition of isoprenylation.
AB  - To investigate the potential determinants of the pleiotropic effects of statins,
      we measured NK cell cytotoxicity in samples from normal subjects and patients,
      including patients receiving statin therapy. In a multivariate analysis, NK cell
      cytotoxicity was related to total plasma cholesterol concentration rather than
      statin use. In vitro, we investigated the role of lipid modification,
      specifically the effects on membrane rafts and raft-dependent signal
      transduction. We demonstrate that statins reduce NK cell cytotoxicity and that
      membrane cholesterol depletion by cyclodextrins has a similar effect. In
      contrast, isoprenyl transferase inhibitors had little or no effect on NK cell
      function. We hypothesise that the pleiotropic effects of statins reflect changes
      in membrane cholesterol and, specifically, the density of membrane rafts.
      Moreover, there is likely to be a relationship between membrane cholesterol,
      membrane rafts and cell function that may be involved in the pathogenesis of
      cardiovascular and metabolic diseases.

PMID- 16814296
TI  - Resistin, acute coronary syndrome and prognosis results from the AtheroGene
      study.
AB  - OBJECTIVE: Resistin, an adipocyte and macrophage derived cytokine, causes insulin
      resistance and glucose intolerance. We investigated the impact of resistin as a
      diagnostic marker in patients with acute coronary syndrome and its prognostic
      value for future cardiovascular events. METHODS: Resistin levels were determined
      in 1153 patients with stable angina (SAP), 380 patients with unstable angina, 278
      patients with non-ST-elevation myocardial infarction (NSTEMI) and 111 patients
      with ST-elevation myocardial infarction (STEMI). All patients have been followed
      up for a median follow-up of 2.6 years. During follow-up, 70 patients died from
      cardiovascular causes. RESULTS: Compared to SAP, resistin levels (5.1 ng/mL in
      SAP) were elevated in patients with angina at rest (5.89 ng/mL, P=0.001), in
      patients with NSTEMI (6.00 ng/mL, P<0.001), and in patients with STEMI (5.98
      ng/mL, P<0.001). Resistin levels rose at 3-6h after chest pain onset (5.46
      ng/mL), persisted elevated among those individuals presenting between 6 and 12h
      after chest pain onset (5.57 ng/mL) and peaked in individuals presenting more
      than 12h after chest pain onset (5.74 ng/mL). An increase of one standard
      deviation of resistin levels was associated with a 1.22-fold (95% CI 1.04-1.43;
      P=0.02) risk for future fatal cardiovascular events in a model adjusted for risk
      factors and clinical and therapeutic variables. When adjustment for renal
      function was applied, this association lost its statistical significance.
      CONCLUSIONS: Resistin levels are elevated in patients presenting with unstable
      angina, NSTEMI and STEMI and might play a role as a diagnostic marker. In
      addition, systemic resistin level is moderately associated with future
      cardiovascular death in patients with documented coronary artery disease.

PMID- 16814297
TI  - Association between TNF and IL-1 bloc polymorphisms and plasma MCP-1
      concentration.
AB  - BACKGROUND: Circulating MCP-1 concentration was found to be increased in
      cardiovascular diseases and is of high interest in the list of biomarkers of
      atherosclerosis. TNF-alpha, LT-alpha, IL-1alpha and IL-1beta are four
      proinflammatory cytokines that regulate MCP-1 concentration in vitro. We
      hypothesized that specific genetic polymorphisms in TNF, LTA, IL-1A and IL-1B
      genes could modulate plasma MCP-1 concentration. METHODS: Plasma MCP-1
      concentration was quantified with a biochip array analyzer in 395 adults from the
      Stanislas family study. TNF -308G>A, LTA 252A>G (A=TNFB2, G=TNFB1), IL-1A -889C>T
      and IL-1B 3954C>T were genotyped with a prototypic multilocus genotyping assay.
      RESULTS: Among the four polymorphisms studied only LTA 252A>G and TNF -308G>A
      were significantly associated with plasma MCP-1 concentration (p=0.005 and
      p=0.038, respectively) after adjustment for covariates (age, sex, smoking,
      monocyte count and hematocrit). Carriers of the 252A allele or the -308G had
      lower MCP-1 concentrations than carriers of the 252G or the -308A alleles,
      respectively. Moreover, as TNF and LTA genes were in linkage disequilibrium, the
      TNF bloc haplotypes were compared with respect to MCP-1 concentration, and a
      significant association (p=0.021) was observed, due only to the LTA polymorphism.
      This association remained significant even after adjustment for TNF-alpha and hs
      CRP concentrations. CONCLUSION: A functional polymorphism within the TNF bloc
      could modulate MCP-1 concentration and seems more likely to be near to the LTA
      252A>G polymorphism than to the TNF -308G>A one. In addition, the association
      found in healthy French adults is independent of other actors of inflammation
      such as TNF-alpha and hs-CRP.

PMID- 16814298
TI  - A deformation gradient decomposition method for the analysis of the mechanics of
      morphogenesis.
AB  - A new finite element model is proposed for the analysis of the mechanical aspects
      of morphogenesis and tested on the biologically well studied gastrulation
      phenomenon, in particular ventral furrow invagination of the Drosophila
      melanogaster embryo. A set of mechanisms are introduced in the numerical model,
      which lead to the observed deformed shapes. We split the total deformation into
      two parts: an imposed active deformation, and an elastic deformation superimposed
      onto the latter. The active deformation simulates the effects of apical
      constriction and apico-basal elongation. These mechanisms are associated with
      known gene expressions and so in this way we attempt to bridge the well explored
      signalling pathways, and their associated phenotypes in a mechanical model. While
      the former have been studied in depth, much less can be said about the forces
      they produce and the mechanisms involved. From the numerical results, we are able
      to test different plausible mechanical hypotheses that generate the necessary
      folding observed in the invagination process. In particular, we conclude that
      only certain ratios between both modes (apical constriction and apico-basal
      elongation) can successfully reproduce the invagination process. The model also
      supports the idea that this invagination requires the contribution of several
      mechanisms, and that their redundancy provides the necessary robustness.

PMID- 16814299
TI  - Zwitterionic stationary phase with covalently bonded phosphorylcholine type
      polymer grafts and its applicability to separation of peptides in the hydrophilic
      interaction liquid chromatography mode.
AB  - A novel phosphorylcholine type zwitterionic stationary phase was synthesized by
      graft polymerization of 2-methacryloyloxyethyl phosphorylcholine onto the surface
      of porous silica particles. The resulting material possesses both negatively
      charged phosphoric acid and positively charged quaternary ammonium groups, which
      renders it a low net charge over a wide pH range. The composition of the surface
      grafts were determined by elemental analysis and solid state NMR, and the surface
      charge (zeta-potential) in different buffer solutions were measured using photon
      correlation spectroscopy. Separation of several peptides was investigated on
      packed columns in the hydrophilic interaction liquid chromatography (HILIC)
      separation mode. It was shown that small peptides can be separated based on
      hydrophilic interaction and ionic interaction between the stationary phase and
      analyte. The organic solvent composition, the pH and the salt concentration of
      the eluent have strong effects on the retention time. Compared to native silica
      before grafting, the newly synthesized zwitterionic material gave more stable
      retention times for basic peptides over pH range 3-7 due to elimination of the
      dissociation of silanol groups.

PMID- 16814300
TI  - Economic appraisal of supercritical fluid extraction of refined cashew nut shell
      liquid.
AB  - This manuscript summarises the techno-economic feasibility of refined cashew nut
      shell liquid (CNSL). A simple mass transfer based mathematical model for the
      yield prediction is presented. The process parameters and extraction time for
      maximum profit and purity of the product were optimized. The optimum extraction
      time for maximum profit and purity was found to be 0.9h at 300 bar and 323 K. The
      influence of the different costs, such as fixed cost, raw material cost, labor
      cost, utility cost, etc. on profit and cost of production of the extract is also
      presented.

PMID- 16814301
TI  - The rule parameters in liquid adsorption chromatography of polymer homologous
      series and their determination.
AB  - The separation of polymer homologous series is governed by two rule parameters:
      the interaction parameter c of the repeat unit and the sorbent surface S
      (relation of pore volume to pore diameter). The interaction parameter is
      independent on column dimensions and pore diameter. In a plot of elution volumes
      Vn versus the difference DeltaV =Vn -Vn-1 in elution volumes of consecutive
      oligomers, straight lines are obtained, the intercept of which yields the
      accessible volume. Using the accessible volume as the hold-up volume in the
      calculation of the retention factor k, a strictly linear dependence of ln k
      versus the number of the repeat units n is observed (Martin's plot). The
      interaction parameter c can be determined experimentally by three different
      approaches: from the slope in a plot of V versus DeltaV, from the slope in
      Martin's plot (ln k versus n), and from the intercept in a plot of ln(DeltaV)
      versus n. The pore surface is obtained from the intercept in Martin's plot (ln k
      versus n) or the intercept in a plot of ln(DeltaV) versus n. The results obtained
      by the different approaches agree very well. The theoretical predictions are
      verified by comparison with the experimental data obtained on columns with
      different pore diameter and pore volume and thus, different pore surface at
      conditions corresponding to the same interaction parameter.

PMID- 16814302
TI  - Preparative production and separation of 2-acetamido-2-deoxymannopyranoside
      containing saccharides using borate-saturated polyolic exclusion gels.
AB  - A new separation method based on the combination of exclusion and ion exchange
      chromatography in borate buffer was developed. It allows semi-preparatory and
      preparatory separation of isobaric N-acylhexosamines (C-2 epimers) and
      corresponding methyl glycosides (anomers and tautomers). Three types of polyolic
      gels were tested for these separations. Ion-exchange HPLC was used as a rapid and
      reliable method for the quantification of the respective analytes. NMR studies of
      the interactions of N-acetylhexosamines with borate confirmed the importance of a
      proper stereochemical arrangement of acetamido sugars for their interactions with
      borate anions.

PMID- 16814303
TI  - Determination of biogenic amines in wines by ion-pair liquid chromatography and
      post-column derivatization with 1,2-naphthoquinone-4-sulphonate.
AB  - A liquid chromatographic method with post-column derivatization for the
      determination of biogenic amines in wines is proposed. The method is based on the
      separation of amines by ion-pair chromatography using sodium heptanesulfonate
      (SHS) and on-line labeling of analytes with 1,2-naphthoquinone-4-sulfonate. The
      principal factors influencing the separation (acetonitrile and SHS concentration)
      have been considered for the optimization of the elution gradient through
      factorial design and multicriteria decision-making. Figures of merit have been
      established using red wine samples. Detection limits range from 0.2 to 3 mg L(
      1), the peak area run-to-run repeatability from 1.6 to 4.6% and the retention
      time repeatability lower than 1.2%. Recoveries ranging from 92 and 108% prove the
      accuracy of the method for determining ethanolamine, ethylamine, histamine and
      tyramine in commercial red wines. The proposed method has been applied to the
      analysis of wines from different Spanish regions.

PMID- 16814304
TI  - Enantioselectivity of vesicle-forming chiral surfactants in capillary
      electrophoresis. Role of the surfactant headgroup structure.
AB  - Two vesicle-forming single-tailed amino acid derivatized surfactants sodium N-[4
      n-dodecyloxybenzoyl]-L-leucinate (SDLL) and sodium N-[4-n-dodecyloxybenzoyl]-L
      isoleucinate (SDLIL) have been synthesized and used as pseudo-stationary phase in
      micellar electrokinetic chromatography to evaluate the role of steric factor of
      amino acid headgroup and hydrophobic/hydrophilic interactions for enantiomeric
      separations. The aggregation behavior of the surfactants has been studied in
      aqueous buffered solution using surface tension and fluorescence probe
      techniques. Results of these studies have suggested formation of vesicles in
      aqueous solutions. Microenvironment of the vesicle, which determines the depth of
      penetration of the analytes into vesicle was determined by fluorescence probe
      technique using pyrene, N-phenyl-1-naphthylamine (NPN), and 1,6-diphenyl-1,3,5
      hexatriene (DPH) as probe molecules. Atropisomeric compounds (+/-)-1,1'-bi-2
      naphthol (BOH), (+/-)-1,1'-binaphthyl-2,2'-diamine (BDA), (+/-)-1,1'-binaphthyl
      2,2'-diylhydrogen phosphate (BNP) and Troger's base (TB) and chiral compound
      benzoin (BZN) has been enantioseparated. The separations were optimized with
      respect to surfactant concentration, pH, and borate buffer concentration. SDLL
      was found to provide better resolution for BOH, BNP, and BZN. On the other hand,
      SDLIL offers better resolution for BDA. The chromatographic results have been
      discussed in the light of the aggregation behavior of the surfactants and the
      interaction of the solutes with the vesicles.

PMID- 16814305
TI  - Improved native UV laser induced fluorescence detection for single cell analysis
      in poly(dimethylsiloxane) microfluidic devices.
AB  - Single cell analytics is a key method in the framework of proteom research
      allowing analyses, which are not subjected to ensemble-averaging, cell-cycle or
      heterogeneous cell-population effects. Our previous studies on single cell
      analysis in poly(dimethylsiloxane) microfluidic devices with native label-free
      laser induced fluorescence detection [W. Hellmich, C. Pelargus, K. Leffhalm, A.
      Ros, D. Anselmetti, Electrophoresis 26 (2005) 3689] were extended in order to
      improve separation efficiency and detection sensitivity. Here, we particularly
      focus on the influence of poly(oxyethylene) based coatings on the separation
      performance. In addition, the influence on background fluorescence is studied by
      the variation of the incident laser power as well as the adaptation of the
      confocal volume to the microfluidic channel dimensions. Last but not least, the
      use of carbon black particles further enhanced the detection limit to 25 nM,
      thereby reaching the relevant concentration ranges necessary for the label-free
      detection of low abundant proteins in single cells. On the basis of these
      results, we demonstrate the first electropherogram from an individual Spodoptera
      frugiperda (Sf9) cell with native label-free UV-LIF detection in a microfluidic
      chip.

PMID- 16814306
TI  - A method for the low-level (ng g(-1)) determination of perfluorooctanoate in
      paper and textile by liquid chromatography with tandem mass spectrometry.
AB  - The determination of perfluorooctanoate (PFO) in articles of commerce has become
      increasingly important to understand if treated products are a possible source of
      PFO. An LC-MS/MS method for the determination of PFO in paper and textile using a
      dual labeled 13C-PFOA internal standard was successfully developed and validated.
      Residues of PFO were determined using an isocratic, reversed-phase high
      performance liquid chromatography (HPLC) method with an ammonium acetate/methanol
      buffer. Ions monitored were 413 (parent) and 369 (daughter) for PFO and 415
      (parent) and 370 (daughter) for dual labeled 13C-PFOA internal standard. As a
      precaution against ubiquitous PFO that occasionally occurs in mobile phase or
      instrument components, two Hypercarb cartridges (4 mm) were placed before the
      HPLC injector. Any PFO that was captured by the cartridges was removed before
      each injection by flushing the system with 100% methanol prior to equilibration
      with the isocratic mobile phase. Overall recovery and standard deviation over a 3
      day validation regimen for samples (n=54-55) fortified with PFOA at 5, 50, and
      200 ng g(-1) were 114+/-4.9% for textile and 110+/-7.6% for paper. The results
      also established a limit of detection (LOD) of 1 ng g(-1) in textile and 2 ng g(
      1) in paper based upon S/N of the 5.0 ng g(-1) fortification versus the untreated
      paper and textile.

PMID- 16814307
TI  - Screening of citalopram, fluoxetine and their metabolites in human urine samples
      by gas chromatography-mass spectrometry. A global robustness/ruggedness study.
AB  - Capillary gas chromatography with mass spectrometry detection in SIM mode (GC-MS
      SIM) has been used for the analysis of citalopram (CIT), fluoxetine (FLX), and
      all of their metabolites in urine samples. The instrumental parameters affecting
      GC separation and MS-SIM detection were investigated. A validation procedure was
      performed on urine matrix and a simultaneous robustness/ruggedness evaluation is
      also presented in this paper. An optimized solid-phase extraction (SPE) has been
      applied, reaching in this way to limits of detection (LODs) between 0.7 ng L(-1)
      (CIT) and 33.6 microg L(-1) (CIT-PA). A pharmacokinetic screening in clinical
      urine samples has been also carried out.

PMID- 16814308
TI  - Context-dependent effects on the hydrophilicity/hydrophobicity of side-chains
      during reversed-phase high-performance liquid chromatography: Implications for
      prediction of peptide retention behaviour.
AB  - The present study set out to investigate whether observed relative
      hydrophilicity/hydrophobicity values of positively charged side-chains (with Lys
      and Arg as representative side-chains) or hydrophobic side-chains (with Ile as
      the representative side-chain) were context-dependent, i.e., did such measured
      values vary depending on characteristics of the peptides within which such side
      chains are substituted (overall peptide hydrophobicity, number of positive
      charges) and/or properties of the mobile phase (anionic counterions of varying
      hydrophobicity and concentration)? Reversed-phase high-performance liquid
      chromatography (RP-HPLC) was applied to two series of four synthetic peptide
      analogues (+1, +2, +3 and +4 net charge), the only difference between the two
      peptide series being the substitution of one hydrophobic Ile residue for a Gly
      residue, in the presence of anionic ion-pairing reagents of varying
      hydrophobicity (HCOOH approximately H3PO4 < TFA < PFPA < HFBA) and concentration
      (2-50 mM). RP-HPLC of these peptide series revealed that the relative
      hydrophilicity of Lys and Arg side-chains in the peptides increased with peptide
      hydrophobicity. In addition the relative hydrophobicity of Ile decreased
      dramatically with an increase in the number of positive charges in the peptide,
      this hydrophobicity decrease being of greater magnitude as the hydrophobicity of
      the anionic ion-pairing reagent increased. These results have significant
      implications in the prediction of peptide retention times for proteomic
      applications.

PMID- 16814310
TI  - Simple approach for the determination of brominated flame retardants in
      environmental solid samples based on solvent extraction and solid-phase
      microextraction followed by gas chromatography-tandem mass spectrometry.
AB  - A viable approach for the analysis of polybrominated biphenyls (PBBs) and
      polybrominated diphenyl ethers (PBDEs) in sewage sludge samples is presented in
      this paper. The proposed method combines ultrasound-assisted extraction (UAE) of
      the solid sample and headspace solid-phase microextraction (HS-SPME) of the
      obtained extract, followed by gas chromatography coupled to tandem mass
      spectrometry (GC-MS-MS) analysis. Different parameters affecting the extraction
      process are evaluated and optimized. The addition of a small amount of Florisil
      to the sample during UAE provides a significant improvement of the
      chromatographic background and, at the same time, a much more efficient HS-SPME.
      Extensive method validation is performed using real sewage sludge samples. The
      proposed method exhibits good performance in terms of linearity and precision,
      with recoveries exceeding 92% and limits of detection in the sub ng g(-1) level.
      Practical applicability is demonstrated through the analysis of real contaminated
      sewage sludge and sediment samples in which some of the target PBDEs are detected
      and quantified. This proposed combined methodology represents a large time-saving
      when compared to other classic multi-step solvent extraction methods and it
      constitutes a suitable approach for the analysis of the target compounds in
      environmental complex solid samples.

PMID- 16814309
TI  - First identification of benzo[ghi]naphtho[8,1,2-bcd]perylene as a product of fuel
      pyrolysis, using high-performance liquid chromatography with diode-array
      ultraviolet-visible absorbance detection and mass spectrometry.
AB  - We present HPLC/UV/MS evidence to support the identification of
      benzo[ghi]naphtho[8,1,2-bcd]perylene as a product of supercritical toluene
      pyrolysis. Mass spectral data confirm that compound I-eluting in between co
      eluting benzo[a]coronene/phenanthro[5,4,3,2-efghi]perylene and
      benzo[pqr]naphtho[8,1,2-bcd]perylene, all three of which have been unequivocally
      identified as C(28)H(14) products of toluene pyrolysis-is also a C(28)H(14)
      product component. The UV spectrum of compound I is presented, and indicates that
      it is a benzenoid polycyclic aromatic hydrocarbon (PAH). Five of the eight
      benzenoid C(28)H(14) PAH isomers have published UV spectra, and characteristics
      of the remaining three are deduced from annelation theory. Only one of these
      compounds, benzo[ghi]naphtho[8,1,2-bcd]perylene, is predicted to have a UV
      spectrum with characteristics that we find in the spectrum of compound I. In
      addition, benzo[ghi]naphtho[8,1,2-bcd]perylene is the only benzenoid C(28)H(14)
      isomer whose length-to-breadth ratio is consistent with the HPLC retention time
      of compound I. The reaction mechanism through which benzo[ghi]naphtho[8,1,2
      bcd]perylene is formed in this environment is shown, and is consistent with
      reaction pathways of other large PAH found in this product mixture.

PMID- 16814311
TI  - Determination of triphenylphosphine oxide in active pharmaceutical ingredients by
      hollow-fiber liquid-phase microextraction followed by reversed-phase liquid
      chromatography.
AB  - A versatile procedure has been developed and validated for the determination of
      triphenylphosphine oxide (TPPO) at low levels in various active pharmaceutical
      ingredients (APIs). This procedure incorporates the use of the novel hollow-fiber
      liquid-phase microextraction (LPME) for the measurement of this potential process
      related impurity in aqueous solutions of APIs. A small volume (40 microL) of 1
      octanol contained within a hollow polypropylene fiber is used for the extraction
      of TPPO from low pH aqueous API solutions. More than a 100-fold increase in the
      TPPO concentration is obtained without additional evaporation of the extract.
      Experimental parameters of the extraction procedure were investigated to optimize
      extraction efficiency and minimize sample matrix interference. Using HPLC/UV as
      the end analysis technique, the procedure was validated for TPPO in the
      concentration range of 3-16 microg/L with an API present at 1500 mg/L. The
      versatility of the method was demonstrated by applying the procedure to the
      analysis of APIs with different molecular structures. This simple LPME procedure
      is inexpensive and offers appropriate sensitivity for the intended use while
      providing several advantages over other analysis methods for pharmaceutical
      samples.

PMID- 16814312
TI  - Fast screening of pesticide multiresidues in aqueous samples by dual stir bar
      sorptive extraction-thermal desorption-low thermal mass gas chromatography-mass
      spectrometry.
AB  - A method for fast screening of pesticide multiresidues in aqueous samples using
      dual stir bar sorptive extraction-thermal desorption-low thermal mass gas
      chromatography-mass spectrometry (dual SBSE-TD-LTM-GC-MS) has been developed.
      Recovery of 82 pesticides - organochlorine, carbamate, organophosphorous,
      pyrethroid and others - for the SBSE was evaluated as a function of octanol-water
      distribution coefficients (log K(o/w): 1.7-8.35), sample volume (2-20 mL), salt
      addition (0-30% NaCl), and methanol addition (0-20%). The optimized method
      consists of a dual SBSE performed simultaneously on respectively a 20-mL sample
      containing 30% NaCl and a 20-mL sample without modifier (100% sample solution).
      One extraction with 30% NaCl is mainly targeting solutes with low K(o/w) (log
      K(o/w)<3.5) and another extraction with unmodified sample solution is targeting
      solutes with medium and high K(o/w) (log K(o/w)>3.5). After extraction, the two
      stir bars are placed in a single glass desorption liner and are simultaneously
      desorbed. The desorbed compounds are analyzed by use of LTM-GC-MS with fast
      temperature programming (75 degrees C min(-1)) using a 0.18 mm i.d. narrow-bore
      capillary column and fast scanning (10.83 scan s(-1)) using quadrupole MS. The
      method showed good linearity (r(2)>0.9900) and high sensitivity (limit of
      detection: <10 ng L(-1)) for most of the target pesticides. The method was
      applied to the determination of pesticides at nanograms per liter levels in river
      water and brewed green tea.

PMID- 16814313
TI  - Rheological properties and particle behaviors of a nondilute colloidal dispersion
      composed of ferromagnetic spherocylinder particles subjected to a simple shear
      flow: analysis by means of mean-field approximation for the two typical external
      magnetic field directions.
AB  - We have analyzed the orientational distributions and rheological properties of a
      nondilute colloidal dispersion composed of ferromagnetic spherocylinder particles
      subjected to a simple shear flow. In order to understand the effects of the
      magnetic interactions between the particles, we have applied the mean-field
      theory to a nondilute colloidal dispersion for the two typical external magnetic
      field directions, that is, the direction parallel to the shear flow and the
      direction parallel to the angular velocity vector of the shear flow. The main
      results are summarized as follows. The particle-particle interactions suppress
      the Brownian motion of the particles and, therefore, make the particles incline
      toward the same direction. For the magnetic direction parallel to the shear flow,
      the influence of the particle-particle interactions makes the peak of the
      orientational distribution sharper and higher. The viscosity generally increases
      as the interactions between particles become stronger in the case where the
      effects of the shear flow and magnetic field are relatively small. For the
      magnetic direction parallel to the angular velocity vector of the shear flow, the
      influence of the particle-particle interactions on the orientational distribution
      appears significantly, when the influences of the shear flow and magnetic field
      are not so strong that the particles can be aligned sufficiently to form stable
      chainlike clusters in a certain direction.

PMID- 16814314
TI  - Surface phase behavior of di-n-tetradecyl hydrogen phosphate in Langmuir
      monolayers at the air-water interface.
AB  - Surface phase behavior of di-n-tetradecyl hydrogen phosphate, DTP, has been
      studied by measuring pi-A isotherms with a film balance and observing monolayer
      morphology with a Brewster angle microscopy (BAM) at different temperatures. A
      generalized phase diagram, which shows a triple point for gas (G), liquid
      expanded (LE) and liquid-condensed (LC) phases at about 32 degrees C, is
      constructed for the amphiphile. Below the triple point, a first-order G-LC phase
      transition has been shown to occur, whereas a first-order G-LE phase transition
      followed by another first-order LE-LC transition has been found to take place at
      a temperature above the triple point. The amphiphile shows the fingering LC
      domains with uniform brightness indicating the presence of untilted molecules.
      The domain shapes are independent of the change in temperature and compression
      rate. The existence of similar fingering domains over a wide range of temperature
      is rather uncommon in the monolayer systems and is considered to be due to the
      restricted movement of the molecules incorporating into the LC phase. Because the
      two-alkyl chains are directly attached to two covalent bonds of the phosphate
      head group, the rearrangement of the molecules, which is an essential condition
      for the circular domain formation, needs the movement of the whole molecules
      including the hydration sphere. The difficulty related to such a movement of the
      molecules causes fingering domains, which are independent of external variables.

PMID- 16814315
TI  - Competitive sorption of Na(+) and Ca(2+) ions on unbleached kraft fibres--a
      kinetics and equilibrium study.
AB  - In a binary system the sorption of Na(+) and Ca(2+) by kraft pulps follows a
      second order kinetics, and the isotherms follow the Langmuir model. The sorption
      capacity is dependent on pH and temperature. The thermodynamic parameters
      indicate that the sorption is exothermic and spontaneous. In a single-component
      system, the sorption capacity of the kraft pulp for Na(+) and Ca(2+) increases
      with the degree of dissociation of ionizable cellulosic components of the kraft
      pulp fibres. In a binary system the exchange of Na(+) and Ca(2+) is highly
      dependent on pH. SEM and X-ray analysis indicated that at pH above 11.0 calcium
      forms a precipitate bound to the surface of the fibres.

PMID- 16814316
TI  - Film-pore-concentration-dependent surface diffusion model for the adsorption of
      dye onto palm kernel shell activated carbon.
AB  - The rate of dye adsorption from aqueous effluents onto palm kernel shell (PKS)
      activated carbon has been studied experimentally using the batch adsorption
      method. The adsorption rates of methylene blue on PKS for systems of different
      initial dye concentrations are modeled using a film-pore-concentration dependent
      surface diffusion (FPCDSD) model. The FPCDSD model is sufficiently general and
      can be reduced easily to describe other simplified models. Using the FPCDSD
      model, only a single set of mass transfer parameters is required to describe the
      methylene blue/PKS system for different initial concentrations. A different set
      of mass transfer parameters are needed to obtain the best fitting if the pore
      diffusion is not included in the model.

PMID- 16814317
TI  - Stuttering in adults: the acoustic startle response, temperamental traits, and
      biological factors.
AB  - The purpose of this study was to investigate the relation between stuttering and
      a range of variables of possible relevance, with the main focus on neuromuscular
      reactivity, and anxiety. The explorative analysis also included temperament,
      biochemical variables, heredity, preonset lesions, and altered auditory feedback
      (AAF). An increased level of neuromuscular reactivity in stuttering adults has
      previously been reported by [Guitar, B. (2003). Acoustic startle responses and
      temperament in individuals who stutter. Journal of Speech Language and Hearing
      Research, 46, 233-240], also indicating a link to anxiety and temperament. The
      present study included a large number of variables in order to enable analysis of
      subgroups and relations between variables. Totally 32 stuttering adults were
      compared with nonstuttering controls. The acoustic startle eyeblink response was
      used as a measure of neuromuscular reactivity. No significant group difference
      was found regarding startle, and startle was not significantly correlated with
      trait anxiety, stuttering severity, or AAF. Startle was mainly related to calcium
      and prolactin. The stuttering group had significantly higher scores for anxiety
      and childhood ADHD. Two subgroups of stuttering were found, with high versus low
      traits of childhood ADHD, characterized by indications of preonset lesions versus
      heredity for stuttering. The study does not support the view that excessive
      reactivity is a typical characteristic of stuttering. The increased anxiety is
      suggested to mainly be an effect of experiences of stuttering. LEARNING OUTCOMES:
      As a result of reading this article, the reader will be able to: (a) critically
      discuss the literature regarding stuttering in relation to acoustic startle,
      anxiety, and temperament; (b) describe the effect of calcium on neuromuscular
      reactivity; (c) discuss findings supporting the importance of early neurological
      incidents in some cases of stuttering, and the relation between such incidents
      and traits of ADHD or ADD; and (d) discuss the role of genetics in stuttering.

PMID- 16814318
TI  - A high throughput electrochemiluminescent cell-binding assay for therapeutic anti
      CD20 antibody selection.
AB  - A cell-based ELISA using suspension WIL2 cells in 96-well format was previously
      developed for measuring relative binding affinities of humanized anti-CD20
      variants. We further developed a new cell-binding assay that uses high binding
      capacity carbon electrode plates for rapid attachment of suspension WIL2 cells
      and electrochemiluminescence for detection. Compared to the cell-based ELISA,
      which requires centrifugation for the manual wash steps, significant improvement
      in assay throughput was achieved by using a microplate washer. The assay can be
      performed on both 96- and 384-well plates with a standard curve range of 2.74
      2000 ng/ml, which is wider than the range of 15.6-1000 ng/ml for the cell-based
      ELISA. Using CD20 expressing CHO cell clones, surface expression of >or=33,000
      CD20 molecules was sufficient to obtain a dose-response curve in 384-well format.
      Relative affinities of 15 humanized variants correlated well (r(2)=0.94) between
      electrochemiluminescent cell-binding assay and cell-based ELISA. A competitive
      assay format, using mouse anti-CD20 antibody as the tracer, with a dose-response
      range of 27.4-20,000 ng/ml was also developed. The new cell-binding assay method
      can be used to efficiently support humanization process for selection of anti
      CD20 antibody drug candidates and to characterize antibody binding to other cell
      surface proteins.

PMID- 16814319
TI  - A SERCA2 pump with an increased Ca2+ affinity can lead to severe cardiac
      hypertrophy, stress intolerance and reduced life span.
AB  - Abnormal Ca(2+) cycling in the failing heart might be corrected by enhancing the
      activity of the cardiac Ca(2+) pump, the sarco(endo)plasmic reticulum Ca(2+)
      ATPase 2a (SERCA2a) isoform. This can be obtained by increasing the pump's
      affinity for Ca(2+) by suppressing phospholamban (PLB) activity, the in vivo
      inhibitor of SERCA2a. In SKO mice, gene-targeted replacement of SERCA2a by
      SERCA2b, a pump with a higher Ca(2+) affinity, results in cardiac hypertrophy and
      dysfunction. The stronger PLB inhibition on cardiac morphology and performance
      observed in SKO was investigated here in DKO mice, which were obtained by
      crossing SKO with PLB(-/-) mice. The affinity for Ca(2+) of SERCA2 was found to
      be further increased in these DKO mice. Relative to wild-type and SKO mice, DKO
      mice were much less spontaneously active and showed a reduced life span. The DKO
      mice also displayed a severe cardiac phenotype characterized by a more pronounced
      concentric hypertrophy, diastolic dysfunction and increased ventricular
      stiffness. Strikingly, beta-adrenergic or forced exercise stress induced acute
      heart failure and death in DKO mice. Therefore, the increased PLB inhibition
      represents a compensation for the imposed high Ca(2+)-affinity of SERCA2b in the
      SKO heart. Limiting SERCA2's affinity for Ca(2+) is physiologically important for
      normal cardiac function. An improved Ca(2+) transport in the sarcoplasmic
      reticulum may correct Ca(2+) mishandling in heart failure, but a SERCA pump with
      a much higher Ca(2+) affinity may be detrimental.

PMID- 16814320
TI  - Cardiac inflammation contributes to right ventricular dysfunction following
      experimental pulmonary embolism in rats.
AB  - Acute right ventricular (RV) failure following pulmonary embolism (PE) is a
      strong predictor of poor clinical outcome. Present studies test for an
      association between RV failure from experimental PE, inflammation, and
      upregulated chemokine expression. Additional experiments test if neutrophil
      influx contributes to RV dysfunction. PE was induced in male rats by infusing 24
      microm microspheres (right jugular vein) producing mild hypertension (1.3 million
      beads/100 g, PE1.3), or moderately severe hypertension (2.0 million beads/100 g,
      PE2.0). Additional rats served as vehicle sham (0.01% Tween 20, Veh). In vivo RV
      peak systolic pressures (RVPSP) increased significantly, and then declined
      following PE2.0 (51 +/- 1 mm Hg 2 h; 49 +/- 1, 6 h; 44 +/- 1, 18 h). RV generated
      pressure of isolated, perfused hearts was significantly reduced in PE2.0 compared
      with PE1.3 or Veh. MCP-1 protein (ELISA) was elevated 21-fold and myeloperoxidase
      activity 95-fold in RV of PE2.0 compared with Veh or PE1.3. CINC-1, CINC-2, MIP
      2, MCP-1, and MIP-1alpha mRNA also increased in RV of PE2.0. Histological
      analysis revealed massive accumulation of neutrophils (selective esterase stain)
      and monocyte/macrophages (CD68, ED-1) in RV of PE2.0 hearts in regions of myocyte
      damage. Electron microscopy showed myocyte necrosis and phagocytosis by
      inflammatory cells. LV function was normal and did not show increased
      inflammation after PE2.0. Treatment with anti-PMN antibody reduced RV MPO
      activity and prevented RV dysfunction. Conclusions-PE with moderately severe
      pulmonary hypertension (PE2.0) resulted in selective RV dysfunction, which was
      associated with increased chemokine expression, and infiltration of both
      neutrophils and monocyte/macrophages, indicating that a robust immune response
      occurred with RV damage following experimental PE. Experimental agranulocytosis
      reduced RV, suggesting that neutrophil influx contributed to RV damage.

PMID- 16814321
TI  - Structural tolerance versus functional intolerance to mutation of hydrophobic
      core residues surrounding cavities in a parvovirus capsid.
AB  - The structural and functional relevance of amino acid residues surrounding
      cavities within the hydrophobic core of the protein subunits that form the capsid
      of parvoviruses has been investigated. Several of the evolutionarily conserved,
      hydrophobic residues that delimit these cavities in the capsid of the minute
      virus of mice were replaced by other hydrophobic residues that would affect the
      size and/or shape of the cavity. When four or more methylene-sized groups were
      introduced, or six or more groups removed, capsid assembly was drastically
      impaired. In contrast, the introduction or removal of up to three groups had no
      significant effect on capsid assembly or thermostability. However, many of these
      mutations affected a capsid conformational transition needed for viral
      infectivity. Replacement of some polar residues around the largest cavity showed
      that capsid assembly requires a carboxylate buried within this cavity, but both
      aspartate and glutamate are structurally accepted. Again, only the aspartate
      allowed the production of infectious viruses, because of a specific role in
      encapsidation of the viral genome. These observations provide evidence of a
      remarkable structural tolerance to mutation of the hydrophobic core of the
      protein subunits in a viral capsid, and of an involvement of core residues and
      internal cavities in capsid functions needed for infectivity.

PMID- 16814322
TI  - Niemann-Pick C disease in Spain: clinical spectrum and development of a
      disability scale.
AB  - OBJECTIVES: To describe the clinical evolution of Niemann-Pick C disease to
      identify possible factors involved in the diagnosis and severity of the disease.
      METHODS: A clinical database and a severity scale was created to evaluate 45
      patients diagnosed with Niemann-Pick type C in the last 28 years in Spain.
      RESULTS: Complete clinical data were obtained from 30 patients, all were
      confirmed to have mutations in the NPC1 gene. Regarding clinical form, 3 were
      perinatal, 7 severe infantile, 6 late infantile, 11 juvenile and 3 adult.
      Biochemical phenotype was classic in 26. Splenomegaly was present in 28 patients
      (93%) with a wide range of age at detection. The first symptom of neurological
      disease was clumsiness, followed in 2-4 years by cerebellar signs.
      Ophthalmoplegia appeared 2-4 years later and became complete 1-2 years after
      onset. Dysarthria appeared by the time of complete ophthalmoplegia. Diagnosis was
      made before the onset of neurological signs in patients with the severe infantile
      form, at the time of onset of cerebellar signs in the late infantile form and
      complete ophthalmoplegia in late onset forms. CONCLUSIONS: In our series,
      splenomegaly is present in 96% of patients, even in late onset forms during the
      first years of life. Clumsiness in children with otherwise normal motor
      development precedes the onset of ataxia by 2-4 years in Niemann Pick type C. A
      disability scale could be useful for monitoring evolution, establishing possible
      phenotypic correlations and evaluating future therapies.

PMID- 16814323
TI  - Are dementia and depression in Parkinson's disease related?
AB  - INTRODUCTION: Depression and dementia are common problems in PD. As the
      depression and dementia of PD share many symptoms such as apathy, anhedonia,
      anergia, and agitation, it is reasonable to ask if they are related. METHODS: 106
      consecutive PD patients, unselected for depression or dementia were evaluated for
      depression using the Hamilton Depression Scale (Ham-D21). They were also
      evaluated using a modified neuropsychiatric inventory (NPI). Following the above,
      100 consecutive PD patients were evaluated for dementia using Folstein's Mini
      Mental Status Examination (MMSE). They were also evaluated using the modified
      NPI. RESULTS: 29 of the first series of patients, 27%, were depressed, score of >
      or =14 on the Ham-D21. 8 of the second series of consecutive patients, 18%, were
      demented, score < or =24 on the MMSE. Depressed and demented patients were
      significantly more likely to suffer from apathy, anhedonia, mood lability,
      daytime drowsiness, paranoia, and hallucinations. Demented patients were
      significantly older, had PD longer, were more disabled and more likely to be
      depressed. COMMENT: The commonality of certain symptoms in demented and depressed
      patients suggests that dementia and depression in PD may be related and that, in
      PD depression may be a fore-runner of dementia. Five year follow-up of these
      patients supports this suggestion.

PMID- 16814324
TI  - Modeling the mechanism of metabolic oscillations in ischemic cardiac myocytes.
AB  - Oscillations in energy metabolism have been observed in a variety of cells under
      metabolically deprived conditions such as ischemia. In cardiac ventricular
      myocytes these metabolic oscillations may cause oscillations in the action
      potential duration, creating the potential for cardiac arrhythmias during
      ischemia (O'Rourke, 2000). A mathematical model of the mechanism behind metabolic
      oscillations is developed here. The model consists of descriptions of the
      mitochondrial components that regulate mitochondrial membrane potential (Psi),
      mitochondrial inorganic phosphate concentration, mitochondrial magnesium
      concentration, and cellular NADH and NAD(+) concentrations. Using parameters from
      the experimental literature, the model produces physiological values for these
      both under normoxic (steady state) and ischemic (oscillatory) conditions. The
      model includes the mitochondrial inner membrane anion channel (IMAC), the centum
      picosiemen channel (mCS), the phosphate carrier (PIC), and the respiration driven
      proton pumps. The model suggests that these are the essential components for
      producing oscillations with mCS essential for the rapid depolarization, PIC for
      the recovery from depolarization, and IMAC for the slow depolarization between
      depolarization peaks. A decrease of the inner membrane potential due to ischemia
      or experimental conditions seems to be a triggering factor for the oscillations.
      The model simulates the experimental observations that high levels of
      mitochondrial ADP and ATP abolish the oscillations, as does inhibition of
      electron transport. The model makes predictions on the influence of pH and
      magnesium levels on metabolic oscillations.

PMID- 16814326
TI  - Accumulation of polycyclic aromatic hydrocarbons by Neocalanus copepods in Port
      Valdez, Alaska.
AB  - Sampling zooplankton is a useful strategy for observing trace hydrocarbon
      concentrations in water because samples represent an integrated average over a
      considerable effective sampling volume and are more representative of the sampled
      environment than discretely collected water samples. We demonstrate this method
      in Port Valdez, Alaska, an approximately 100 km(2) basin that receives about 0.5
      2.4 kg of polynuclear aromatic hydrocarbons (PAH) per day. Total PAH (TPAH)
      concentrations (0.61-1.31 microg/g dry weight), composition, and spatial
      distributions in a lipid-rich copepod, Neocalanus were consistent with the
      discharge as the source of contamination. Although Neocalanus acquire PAH from
      water or suspended particulate matter, total PAH concentrations in these
      compartments were at or below method detection limits, demonstrating plankton can
      amplify trace concentrations to detectable levels useful for study.

PMID- 16814325
TI  - Altered neurogenic and mechanical responses to acetylcholine, ATP and substance P
      in detrusor from rat with outlet obstruction.
AB  - The well-known side effects of anticholinergic compounds used to treat urinary
      incontinence caused by detrusor overactivity have addressed the interest on other
      pharmacological intervention. The purpose of the present work was to investigate
      the possible changes in purinergic and cholinergic components of parasympathetic
      neurotransmission in obstructed rat bladders with detrusor overactivity, and to
      examine the effect of the association of suramin, atropine and indomethacin on
      nerve-mediated responses to electrical field stimulation (EFS). Mechanical
      responses to exogenous acetylcholine, ATP and substance P were also evaluated.
      Altered sensitivities to acetylcholine and to the sensory neurotransmitter
      substance P, but unchanged sensitivity to the stable ATP analogue alpha,beta
      methyleneATP were observed in bladders from obstructed rats. Suramin and atropine
      inhibited purinergic and cholinergic components of the neurogenic responses
      evoked by EFS in detrusor strips from control and obstructed rats. Interestingly,
      suramin enhanced the antagonistic effect of atropine on neurogenic responses of
      detrusor strips at all frequencies of stimulation tested. Our results suggest
      that the association between an antimuscarinic drug and an antagonist of P2X
      purinoceptors such as suramin might be helpful to reduce the therapeutic dosage
      of the antimuscarinic drug, along with its side effects. This approach may be of
      interest in the therapy of patients with bladder incontinence caused by detrusor
      overactivity, which do not even respond to a maximal dosage of antimuscarinic
      drug.

PMID- 16814327
TI  - Changes in biodiversity of the extremely polluted Golden Horn Estuary following
      the improvements in water quality.
AB  - Long-term biological data supported by physicochemical parameters were evaluated
      to investigate the biodiversity of the Golden Horn Estuary from the past to the
      present. Limited observations dating back to 60 years ago indicated the existence
      of a diverse community in this small estuary. Unfortunately, in parallel with the
      increase in unplanned settlements and industry around the Golden Horn, pollution
      stress increased since the 1960s. Preliminary studies in the 1990s indicated
      survival of only a couple of pollution-resistant species, in the relatively
      cleaner lower estuary. Following the intensification of rehabilitation studies in
      1998 and particularly after the opening of the floating bridge at the mid
      estuary; a remarkable day-by-day recovery in marine life has begun with the
      improving water quality. Nutrient concentrations decreased markedly; while water
      clarity significantly increased. Fecal coliform values decreased 10(3) fold.
      Phytoplankton composition changed and dense blooms of eukaryotic phytoplankters
      frequently occurred. Hydrogen sulfide almost completely disappeared even during
      the warmest periods of the year and dissolved oxygen concentrations increased.
      All results clearly depicted that the Golden Horn ecosystem shifted to eutrophic
      conditions from an anoxic environment. SCUBA dives in 2002, documented the level
      of diversification of life in the Golden Horn. All appropriate substratums were
      intensely covered by macrobenthic forms until the Halic Bridge and filter feeders
      dominated the plankton-rich ecosystem. Achieving the diversity of 1940s is not
      possible since the Black and Marmara seas, influencing water quality of the
      Golden Horn, are also suffering from anthropogenic impacts and are far less
      diverse than their rich diversity in 1940s. However, the Golden Horn is a good
      example that even the most polluted ecosystems can recover when appropriate
      measures are taken.

PMID- 16814328
TI  - Chromosome aberrations in solid tumors have a stochastic nature.
AB  - An important question nowadays is whether chromosome aberrations are random
      events or arise from an internal deterministic mechanism, which leads to the
      delicate task of quantifying the degree of randomness. For this purpose, we have
      defined several Shannon information functions to evaluate disorder inside a tumor
      and between tumors of the same kind. We have considered 79 different kinds of
      solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of
      Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also
      obtained for each solid tumor type in order to correlate data with tumor
      malignance. The results here show that aberration spread is specific for each
      tumor type, with high degree of diversity for those tumor types with worst
      survival indices. Those tumor types with preferential variants (e.g. high
      proportion of a given karyotype) have shown better survival statistics,
      indicating that aberration recurrence is a good prognosis. Indeed, global spread
      of both numerical and structural abnormalities demonstrates the stochastic nature
      of chromosome aberrations by setting a signature of randomness associated to the
      production of disorder. These results also indicate that tumor malignancy
      correlates not only with karyotypic diversity taken from different tumor types
      but also taken from single tumors. Therefore, by quantifying aberration spread,
      we could confront diverse models and verify which of them points to the most
      likely outcome. Our results suggest that the generating process of chromosome
      aberrations is neither deterministic nor totally random, but produces variations
      that are distributed between these two boundaries.

PMID- 16814330
TI  - The pituitary potential for opportunistic breeding in the Cape dune mole-rat,
      Bathyergus suillus.
AB  - In this paper we investigated the effect of sex and season on baseline and post
      GnRH challenge luteinising hormone (LH) levels in a solitary, seasonally breeding
      mole-rat. Circulating basal concentrations of luteinising hormone (LH) were found
      to differ significantly with season in both sexes. However, no significant
      difference was found in circulating basal LH concentration between the sexes
      either within or out of the breeding season. The magnitude of the LH response to
      an exogenous pharmacological overdose of GnRH both in and out of the breeding
      season in males and females respectively was not significant. This finding
      suggests that there is no down regulation of GnRH receptors on the pituitary
      during the non-breeding season. Cape dune mole-rats thus have the potential for
      opportunistic breeding outside of the typical breeding period. We argue that this
      represents an adaptation to limited and brief opportunities for mating in this
      xenophobic and aggressive species.

PMID- 16814329
TI  - Nicotine, but neither the alpha4beta2 ligand RJR2403 nor an alpha7 nAChR subtype
      selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat
      median forebrain bundle.
AB  - Although previous studies suggest nicotine protects against a 6-hydroxydopamine
      (6-OHDA)-induced lesion of the nigrostriatal tract in rats, it is not known
      whether functional motor recovery occurs or which nicotinic acetylcholine
      receptor (nAChR) subtypes mediate this effect. These issues were investigated by
      comparing the effects of the subtype-specific nAChR agonists, RJR2403
      (alpha4beta2 preferring) and (R)-N-(1-azabicyclo[2.2.2.]oct-3-yl)(5-(2
      pyridyl)thiopene-2-carboxamide (Compound A; alpha7-selective) and nicotine given
      30 min prior to and daily for 14 days after a partial 6-OHDA lesion. In vehicle
      treated animals, 6-OHDA (6 microg) produced a 65 +/- 1.8% loss of striatal
      tyrosine hydroxylase (TH) immunoreactivity in the lesion versus intact
      hemisphere. This loss was reduced in animals treated with nicotine (0.6 and 0.8
      mg kg(-1)), reaching significance at the higher dose (36.6 +/- 3.7% loss; P <
      0.01 versus vehicle). Treatment with nicotine (0.6 and 0.8 mg kg(-1)) also
      significantly reduced the number of amphetamine-induced rotations compared to
      vehicle treatment. In contrast, treatment with RJR2403 (0.2 and 0.4 mg kg(-1)) or
      Compound A (10 and 20 mg kg(-1)) reduced neither the degree of amphetamine
      induced rotations nor the loss of striatal TH immunoreactivity. These data
      suggest that whilst nicotine is neuroprotective in this partial lesion model,
      activation of neither the alpha4beta2 nor alpha7 subtypes alone is sufficient to
      provide protection.

PMID- 16814331
TI  - Making sense of food.

PMID- 16814332
TI  - Arabidopsis thaliana beta-Glucosidases BGLU45 and BGLU46 hydrolyse monolignol
      glucosides.
AB  - In higher plants, beta-glucosidases belonging to glycoside hydrolase (GH) Family
      1 have been implicated in several fundamental processes including lignification.
      Phylogenetic analysis of Arabidopsis thaliana GH Family 1 has revealed that
      At1g61810 (BGLU45), At1g61820 (BGLU46), and At4g21760 (BGLU47) cluster with Pinus
      contorta coniferin beta-glucosidase, leading to the hypothesis that their
      respective gene products may be involved in lignification by hydrolysing
      monolignol glucosides. To test this hypothesis, we cloned cDNAs encoding BGLU45
      and BGLU46 and expressed them in Pichia pastoris. The recombinant enzymes were
      purified to apparent homogeneity by ammonium sulfate fractionation and
      hydrophobic interaction chromatography. Among natural substrates tested, BGLU45
      exhibited narrow specificity toward the monolignol glucosides syringin (K(m),
      5.1mM), coniferin (K(m), 7mM), and p-coumaryl glucoside, with relative hydrolytic
      rates of 100%, 87%, and 7%, respectively. BGLU46 exhibited broader substrate
      specificity, cleaving salicin (100%), p-coumaryl glucoside (71%; K(m), 2.2mM),
      phenyl-beta-d-glucoside (62%), coniferin (8%), syringin (6%), and arbutin (6%).
      Both enzymes also hydrolysed p- and o-nitrophenyl-beta-d-glucosides. Using RT
      PCR, we showed that BGLU45 and BGLU46 are expressed strongly in organs that are
      major sites of lignin deposition. In inflorescence stems, both genes display
      increasing levels of expression from apex to base, matching the known increase in
      lignification. BGLU45, but not BGLU46, is expressed in siliques, whereas only
      BGLU46 is expressed in roots. Taken together with recently described monolignol
      glucosyltransferases [Lim et al., J. Biol. Chem. (2001) 276, 4344-4349], our
      enzymological and molecular data support the possibility of a monolignol
      glucoside/beta-glucosidase system in Arabidopsis lignification.

PMID- 16814333
TI  - A preliminary neuropathological study of Japanese encephalitis in humans and a
      mouse model.
AB  - Japanese encephalitis virus is a mosquito-borne flavivirus that causes
      approximately 10000 deaths annually in Asia. After a brief viraemia, the virus
      enters the central nervous system, but the means of crossing the blood-brain
      barrier is uncertain. We used routine histological staining, immunohistology and
      electron microscopy to examine brain material from four fatal human cases, and
      made comparisons with material from a mouse model. In human material there was
      oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular
      necrotic foci, as has been described previously. In addition, there was new
      evidence suggestive of viral replication in the vascular endothelium, with
      endothelial cell damage; this included occasional viral antigen staining, uneven
      binding of the vascular endothelial cells to Ulex europaeus agglutinin I and
      ultrastructural changes. Viral antigen was also found in neurons. There was an
      active astrocytic response, as shown by glial fibrillary acidic protein staining,
      and activation of microglial cells was demonstrated by an increase in major
      histocompatibility complex class II expression. Similar inflammatory infiltrates
      and a microglial reaction were observed in mouse brain tissue. In addition, beta
      amyloid precursor protein staining indicated impaired axonal transport. Whether
      these findings are caused by viral replication in the vascular endothelium or the
      immune response merits further investigation.

PMID- 16814334
TI  - Hymenolepis nana infection: symptoms and response to nitazoxanide in field
      conditions.
AB  - A matched case-control study on clinical symptoms of Hymenolepis nana and an open
      trial of nitazoxanide treatment were conducted in a village on the northern coast
      of Peru. Interview data were obtained from 25 individuals with hymenolepiasis
      only and 46 matched controls. Individuals with other intestinal helminths or
      giardiasis were excluded. Twenty nitazoxanide-treated cases were followed with
      stool examination a month later. There were no significant differences between
      groups in the prevalence of symptoms except headache, which was less frequent in
      the cases. Treatment efficacy was 75%. Hymenolepiasis in this community did not
      have significant impact on specific symptoms.

PMID- 16814335
TI  - Detection and quantification of glucuro- and sulfoconjugated metabolites in human
      urine following oral administration of xenobiotic 19-norsteroids.
AB  - Recently, the endogenous origin of nandrolone (19-nortestosterone) and other 19
      norsteroids has been a focus of research in the field of drug testing in sport.
      In the present study, we investigated metabolites conjugated to a glucuronic acid
      and to a sulfuric acid in urine following administration of four xenobiotic 19
      norsteroids. Adult male volunteers administered a single oral dose (10 mg) of
      each of four 19-norsteroids. Urinary samples collected from 0 to 120 h were
      subjected to methanolysis and beta-glucuronidase hydrolysis and were derivatized
      by N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) before gas chromatography
      mass spectrometry analysis. We confirmed that 19-norandrosterone (19-NA) and 19
      noretiocholanolone (19-NE) were present in both glucuronide (g) and sulfate (s)
      conjugates and 19-norepiandrosterone (19-NEA) was excreted exclusively as a
      sulfate fraction in urine of all 19-norsteroids tested. The overall levels of the
      three metabolites can be ranked as follows: 19-NA(g+s)>19-NE(g+s)>19-NEA(s). The
      concentration profiles of these three metabolites in urine peaked between 2 to
      12h post-administration and declined thereafter until approximately 72-96 h. 19
      NA was most prominent throughout the first 24 h post-administration, except for a
      case in which an inverse relationship was found after 6h post-administration of
      nandrolone. Furthermore, we found that sulfate conjugates were present in both 19
      NA and 19-NE metabolites in urine of all 19-norsteroids tested. The averaged
      total amounts of metabolites (i.e. 19-NA(s+g)+19-NE(s+g)+19-NEA(s)) excreted in
      urine were 38.6, 42.9, 48.3 and 21.6% for nandrolone, 19-nor-4-androsten-3,17
      dione, 19-nor-4-androsten-3beta,17beta-diol and 19-nor-5-androstene-3beta,17beta
      diol, respectively. Results from the excretion studies demonstrate significance
      of sulfate-conjugated metabolites on interpretation of misuse of the 19
      norsteroids.

PMID- 16814336
TI  - Stereoselective synthesis of some 17beta-dihydrooxazinyl steroids, as novel
      presumed inhibitors of 17alpha-hydroxylase-C17,20-lyase.
AB  - 17beta-Dihydrooxazinyl steroids 5a-l and 6a-l were synthetized. The acid
      catalyzed reactions of 21-azidomethyl-20-hydroxy- and 21-hydroxymethyl-20
      azidosteroids with substituted aromatic aldehydes led to the formation of androst
      5-en-3beta-ols substituted in position 17beta with dihydrooxazine residues. The
      inhibitory effects of these compounds on rat testicular C(17,20)-lyase were
      investigated with an in vitro radioincubation technique.

PMID- 16814337
TI  - Competition may determine the diversity of transposable elements.
AB  - Transposable elements are genomic parasites that replicate independently from
      their hosts. They harm their hosts by causing mutations or genomic
      rearrangements, and most organisms have evolved various mechanisms to suppress
      their activity. The evolutionary dynamics of transposons in insects, fish, birds
      and mammals are dramatically different. Mammalian genomes contain few, very
      abundant but relatively inactive transposon strains, while Drosophila and fish
      species harbour diverse strains, which typically have low abundance but are much
      more virulent. We hypothesise that the variation in the diversity and activity of
      transposable elements between various animal genomes is caused by the differences
      in the host defence mechanisms against transposon activity. In recent years RNAi,
      a mechanism capable of gene, virus and transposon silencing has been discovered.
      We model RNAi as a density dependant mechanism of defence, which can cause
      competition among transposons depending on its specificity, and test its
      predictions using the complete Caenorhabditis elegans, Drosophila melanogaster,
      Fugu rubripes, chicken, mouse, rat and human genome sequences.

PMID- 16814338
TI  - Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs
      activation and induction of HO-1 gene expression in rat glioma cells C6.
AB  - In the present study, we examined the protective mechanism of baicalein (BE) and
      its glycoside, baicalin (BI), on hydrogen-peroxide (H(2)O(2))-induced cell death
      in rat glioma C6 cells. Results of the MTT assay, LDH release assay, and
      morphological observation showed that H(2)O(2) addition reduced the viability of
      C6 cells, and this was prevented by the addition of BE but not BI. Incubation of
      C6 cells with BE significantly decreased the intracellular peroxide level induced
      by H(2)O(2) according to flow cytometric analysis using DCHF-DA as a fluorescent
      substrate. Suppression of H(2)O(2)-induced apoptotic events including DNA
      ladders, hypodiploid cells, and activation of caspases 3, 8, and, 9 by BE but not
      BI was identified in C6 cells. The cytotoxicity and phosphorylation of ERK
      proteins induced by H(2)O(2) were blocked by the ERK inhibitor PD98059. Catalase
      addition prevented H(2)O(2)-induced ROS production, ERKs protein phosphorylation,
      and cell death, and BE dose-dependently inhibited H(2)O(2)-induced ERK protein
      phosphorylation in C6 cells. These data suggest that ROS-scavenging activity is
      involved in BE prevention of H(2)O(2)-induced cell death via blocking ERKs
      activation. Additionally, BE but not BI induced heat shock protein 32 (HSP32; HO
      1) protein expression in both time- and dose-dependent manners, but not heme
      oxygenase 2 (HO-2), heat shock protein 70 (HSP70), or heat shock protein 90
      (HSP90) protein expression. In the absence of H(2)O(2), BE induces ERKs protein
      phosphorylation, and HO-1 protein expression induced by BE was blocked by the
      addition of cycloheximide, actinomycin D, and the ERK inhibitor PD98059. The
      addition of the HO inhibitor ZnPP inhibited the protective effect of BE against
      H(2)O(2)-induced cytotoxicity in C6 cells according to the MTT assay and
      apoptotic morphology under microscopic observation, accompanied by blocking the
      ROS-scavenging activity of BE in C6 cells. However, BE treatment was unable to
      protect C6 cells from C2-ceramide-induced cell death. These data indicate that BE
      possesses abilities to inhibit ROS-mediated cytotoxic effects through modulation
      of ERKs activation and induction of HO-1 protein expression. The role of HO-1 in
      ROS-scavenging activity of BE is proposed.

PMID- 16814339
TI  - Kinetics of 3-(4-methylbenzylidene)camphor in rats and humans after dermal
      application.
AB  - The toxicokinetics of 4-MBC after dermal administration were investigated in
      human subjects and in rats. Humans (3 male and 3 female subjects) were exposed to
      4-MBC by topical application of a commercial sunscreen formulation containing 4%
      4-MBC (w/w), covering 90% of the body surface and resulting in a mean dermal 4
      MBC dose of 22 mg/kg bw. In rats, dermal 4-MBC doses of 400 and 2000 mg/kg bw
      were applied in a formulation using an occlusive patch for 24 h. Concentrations
      of 4-MBC and its metabolites were monitored over 96 h in plasma (rats and humans)
      and urine (humans). In human subjects, plasma levels of 4-MBC peaked at 200
      pmol/ml in males and 100 pmol/ml in females 6 h after application and then
      decreased to reach the limit of detection after 24 h (females), respectively, 36
      h (males). After dermal application of 4-MBC, peak plasma concentrations of 3-(4
      carboxybenzylidene)-6-hydroxycamphor were 50-80 pmol/ml at 12 h and of 3-(4
      carboxybenzylidene)camphor were 100-200 pmol/ml at 24 h. In male and female rats,
      peak plasma levels of 4-MBC were 200 (dose of 400 mg/kg bw) and 1 200 pmol/ml
      (dose of 2000 mg/kg bw). These levels remained constant for up to 24-48 h after
      dermal application. Peak plasma concentrations of 3-(4-carboxybenzylidene)-6
      hydroxycamphor were 18,000 pmol/ml (males) and of 3-(4-carboxybenzylidene)camphor
      were 55,000 pmol/ml (females) between 48 and 72 h after application of the high
      dose of 4-MBC. In human subjects, only a small percentage of the dermally applied
      dose of 4-MBC was recovered in the form of metabolites in urine, partly as
      glucuronides. The obtained results suggest a more intensive biotransformation of
      4-MBC in rats as compared to humans after dermal application and a poor
      absorption of 4-MBC through human skin.

PMID- 16814340
TI  - A new toxin from the sea anemone Condylactis gigantea with effect on sodium
      channel inactivation.
AB  - A new peptide toxin exhibiting a molecular weight of 5043Da (av.) and comprising
      47 amino acid residues was isolated from the sea anemone Condylactis gigantea.
      Purification of the peptide was achieved by a multistep chromatographic procedure
      monitoring its strong paralytic activity on crustacea (LD(50) approx.
      1microg/kg). Complete sequence analysis of the toxic peptide revealed the
      isolation of a new member of type I sea anemone sodium channel toxins containing
      the typical pattern of the six cysteine residues. From 11kg of wet starting
      material, approximately 1g of the peptide toxin was isolated. The physiological
      action of the new toxin from C. gigantea CgNa was investigated on sodium currents
      of rat dorsal root ganglion neurons in culture using whole-cell patch clamp
      technique (n=60). Under current clamp condition (CgNa) increased action potential
      duration. This effect is due to slowing down of the TTX-S sodium current
      inactivation, without modifying the activation process. CgNa prolonged the
      cardiac action potential duration and enhanced contractile force albeit at 100
      fold higher concentrations than the Anemonia sulcata toxin ATXII. The action on
      sodium channel inactivation and on cardiac excitation-contraction coupling
      resemble previous results with compounds obtained from this and other sea
      anemones [Shapiro, B.I., 1968. Purification of a toxin from tentacles of the
      anemone C. gigantea. Toxicon 5, 253-259; Pelhate, M., Zlotkin, E., 1982. Actions
      of insect toxin and other toxins derived from the venom of scorpion Androtonus
      australis on isolated giant axons of the cockroach Periplaneta americana. J. Exp.
      Biol. 97, 67-77; Salgado, V., Kem, W., 1992. Actions of three structurally
      distinct sea anemone toxins on crustacean and insect sodium channels. Toxicon 30,
      1365-1381; Bruhn, T., Schaller, C., Schulze, C., Sanchez-Rodriquez, J.,
      Dannmeier, C., Ravens, U., Heubach, J.F., Eckhardt, K., Schmidtmayer, J.,
      Schmidt, H., Aneiros, A., Wachter, E., Beress, L., 2001. Isolation and
      characterization of 5 neurotoxic and cardiotoxic polypeptides from the sea
      anemone Anthopleura elegantissima. Toxicon, 39, 693-702]. Comprehensive analysis
      of the purified active fractions suggests that CgNa may represent the main
      peptide toxin of this sea anemone species.

PMID- 16814341
TI  - Effects of the dinoflagellate Karenia brevis on larval development in three
      species of bivalve mollusc from Florida.
AB  - The effects of Karenia brevis (Wilson clone) on larval survival and development
      of the northern quahog, Mercenaria mercenaria, eastern oyster, Crassostrea
      virginica and bay scallop, Argopecten irradians, were studied in the laboratory.
      Larvae were exposed to cultures of whole and lysed cells, with mean total
      brevetoxin concentrations of 53.8 and 68.9 microgL(-1), respectively. Survival of
      early (3-day-old) larvae was generally over 85% for all shellfish species at K.
      brevis densities of 100 cells ml(-1) or less, and not significantly different
      between whole and lysed culture. At 1000 cells ml(-1), survival was significantly
      less in lysed culture than whole culture for both M. mercenaria and C. virginica.
      Survival of late (7-day-old) larvae in all three species was not significantly
      affected by K. brevis densities of 1000 cells ml(-1) or less. At 5000 cells ml(
      1), however, survival was reduced to 37%, 26% and 19% for A. irradians, M.
      mercenaria and C. virginica, respectively. Development of C. virginica and M.
      mercenaria larvae was protracted at K. brevis densities of 1000 cells ml(-1).
      These results suggest that blooms of K. brevis, and particularly their associated
      brevetoxins, may have detrimental consequences for Florida's shellfisheries by
      disrupting critical larval processes. Special attention should be paid to blooms
      of K. brevis where these shellfish occur naturally or where aquaculture and
      restoration activities are either ongoing or planned.

PMID- 16814342
TI  - Shear elasticity of fluids at low-frequent shear influence.
AB  - The visco-elastic properties of liquids have been investigated using acoustical
      resonance method. Piezoquatrz performed tangential oscillations on the main
      resonance frequency of 74 kHz contacts by the one end of horizontal surface with
      the studied liquid layer covered by quartz cover-plate. So the stagnant shear
      waves are installed in layer. The solution of interaction of piezoquartz-liquid
      layer-cover-plate gives three methods of determination of the real shear modulus
      (G) and the tangent of mechanical loss angle (tan theta) of liquid. The first
      method is realized at smaller thickness of liquid layer then the length of shear
      wave. Liquids of different classes have been studied using this method: polymer
      liquids, oils, glycols and alcohols. The second method is connected with the
      propagation of shear wave in liquid layer, parameters of which are determined the
      G and tan theta. And the third method is based on the determination of limit
      shift of resonance frequencies at completes damping of shear wave in thick layer
      of liquid. All these three methods give satisfactory agreement of results.

PMID- 16814343
TI  - Ultrasonic characterization of granites obtained from industrial quarries of
      Extremadura (Spain).
AB  - The industry of ornamental rocks, such as granites, represents one of the most
      important industrial activities in the region of Extremadura, SW Spain. A
      detailed knowledge of the intrinsic properties of this natural stone and its
      environmental evolution is a required goal in order to fully characterize its
      quality. In this work, two independent NDT acoustic techniques have been used to
      measure the acoustic velocity of longitudinal waves in different prismatic
      granitic-samples of industrial quarries. A low-frequency transceiver set-up,
      based on a high-voltage BPV Steinkamp instrument and two 50 kHz probes, has been
      used to measure pulse travel times by ultrasonic through-transmission testing. In
      complementary fashion, an Erudite MK3 test equipment with an electromagnetic
      vibrator and two piezoelectric sensors has also been employed to measure
      ultrasonic velocity by means of a resonance-based method, using the same types of
      granite varieties. In addition, a comprehensive set of physical/mechanical
      properties have also been analyzed, according to Spanish regulations in force, by
      means of alternative methods including destructive techniques such as strength,
      porosity, absorption, etc. A large number of samples, representing the most
      important varieties of granites from quarries of Extremadura, have been analyzed
      using the above-mentioned procedures. Some results obtained by destructive
      techniques have been correlated with those found using ultrasonic techniques. Our
      experimental setting allowed a complementary characterization of granite samples
      and a thorough validation of the different techniques employed, thus providing
      the industry of ornamental rocks with a non-destructive tool that will facilitate
      a more detailed insight on the properties of the rocks under study.

PMID- 16814344
TI  - Finite element analyzing of underwater receiving sensitivity of PMN-0.33PT single
      crystal cymbal hydrophone.
AB  - This paper introduces a practical design and fabrication of a small hydrophone
      which combines the structure of cymbal-type transducer with the material of PMN
      0.33PT. Finite element method (FEM) is used for the receiving sensitivity
      analysis. Compared with PZT-5A, PMN-0.33PT shows higher receiving voltage
      sensitivity in various designs of the cymbal transducers.

PMID- 16814345
TI  - Generation and detection of acoustic solitons in crystalline slabs by laser
      ultrasonics.
AB  - Acoustic solitons have been recently observed in different systems (Si, Sapphire,
      MgO, alpha-quartz). Such acoustic waves could lead to sub-picosecond acoustic
      pulses. In this paper, we report on the formation of acoustic solitons in a GaAs
      crystalline slab. A short picosecond acoustic pulse is generated by absorption of
      a femtosecond laser pulse in an aluminum thin film deposited on one side of the
      slab. This strain pulse travels through the sample up to the opposite side where
      it is detected by a time delayed laser pulse reflected by an aluminum transducer.
      We use interferometric detection to measure independently the real and imaginary
      parts of the relative change in optical reflectivity induced by the acoustic
      pulse. We find that, at low temperature and with a laser pump pulse energy of 10
      nJ, an acoustic soliton clearly separates from the acoustic pulse in GaAs slab.
      The soliton shape is compared with numerical simulations for different excitation
      conditions. From the very unique properties of solitons, we infer a soliton pulse
      duration of about 2.3 ps which corresponds to a spatial extent of only 12 nm.

PMID- 16814346
TI  - Acoustooptic interaction in science and applications.
AB  - Main results of acousto-optic investigations in physical acoustics of solids
      obtained in Ioffe Physico-Technical Institute during recent yeas are presented.
      Both monocrystals, and glass alloys of different compositions were used as
      objects of researches. The studies were fulfilled in wide ranges of optical
      wavelengths (0.63-10.6 mkm), temperatures (77-400 K) and frequencies (10-1800
      MHz) of bulk and surface acoustic waves.

PMID- 16814347
TI  - Superimposed ultrasonic oscillations in compression tests of aluminium.
AB  - The application of ultrasonics in metal forming applications has been shown to
      reduce the forming load significantly in many research studies. The load
      reduction has been related to the stress superposition effect, rise in
      temperature and change in the friction condition between the specimen and die
      interfaces. This paper reports an investigation into the effects of superimposed
      ultrasonic oscillation of the die in compression tests on aluminium specimens. In
      particular, a finite element model is developed to simulate uniaxial compression
      and to model the effects of a change in the friction boundary condition when
      ultrasonic excitation is applied to the lower platen. The model predictions of
      the stress-strain relationship can be compared with test data to provide some
      insights into the effects of the interfacial condition. The paper shows how the
      analysis of the test data, combined with finite element models of ultrasonic
      compression test simulations, allows some initial conclusions to be drawn
      regarding the influence of the interfacial friction during ultrasonic
      compression.

PMID- 16814348
TI  - Acoustic analysis of bound rubber formed in silica/SBR compounds.
AB  - The compressibility of the bound rubber around the silica particle was evaluated
      by an acoustic technique. The density and the longitudinal wave velocity of a
      silica/SBR compound were measured as a function of the silica content. The
      density increased linearly with the filler content. The longitudinal wave
      velocity was almost constant within the experimental error. The mass ratio of the
      bound rubber to the silica in the silica/SBR compounds was 1.08+/-0.03 kg kg(-1)
      which was measured by a thermal gravimetric analysis (TGA). The partial specific
      adiabatic compressibility of the silica was estimated as (0.1+/-0.5) x 10(-10)
      Pa(-1) on the basis of a three states model. The adiabatic compressibility of the
      bound rubbers in the silica/SBR compounds was (4.6+/-0.5) x 10(-10) Pa(-1). The
      compressibility was almost the same as that of the SBR, and the value was twice
      larger than the compressibility of the bound rubber formed in a CB/SBR composite.

PMID- 16814349
TI  - Porosity estimation of aged mortar using a micromechanical model.
AB  - Degradation of concrete structures located in high humidity atmospheres or under
      flowing water is a very important problem. In this study, a method for ultrasonic
      non-destructive characterization in aged mortar is presented. The proposed method
      makes a prediction of the behaviour of aged mortar accomplished with a three
      phase micromechanical model using ultrasonic measurements. Aging mortar was
      accelerated by immersing the probes in ammonium nitrate solution. Both
      destructive and non-destructive characterization of mortar was performed.
      Destructive tests of porosity were performed using a vacuum saturation method and
      non-destructive characterization was carried out using ultrasonic velocities.
      Aging experiments show that mortar degradation not only involves a porosity
      increase, but also microstructural changes in the cement matrix. Experimental
      results show that the estimated porosity using the proposed non-destructive
      methodology had a comparable performance to classical destructive techniques.

PMID- 16814350
TI  - A new optical method for the detection of in-plane motion of ultrasound
      propagating in metals.
AB  - This paper describes a laser optical technique for the detection of in-plane (IP)
      motion of ultrasonic waves propagating in solids. This interference-based laser
      optical technique includes a tiny square indentation with a width of about 30
      microm on the sample surface and a relatively simple optical arrangement. The
      current technique is applied for the detection of in-plane motions of Lamb waves
      propagating in a thin brass plate. Measurement of S(0) mode dominated by in-plane
      motion in the low fd (frequency times thickness) regime is successfully
      demonstrated with the current technique. The newly proposed non-contact technique
      provides an alternative other than the heterodyne and Fabry-Perot techniques for
      the detection of IP motions with a relatively simple optical arrangement. This
      technique is not readily applicable to general NDE applications, where a position
      scan or an arbitrary selection of inspection location is needed. However, this
      technique can be useful in the areas such as fixed-position ultrasound monitoring
      or laboratory research activities involving optical detection of IP motion.

PMID- 16814351
TI  - A finite element model for ultrasonic cutting.
AB  - Using a single-blade ultrasonic cutting device, a study of ultrasonic cutting of
      three very different materials is conducted using specimens of cheese,
      polyurethane foam and epoxy resin. Initial finite element models are created,
      based on the assumption that the ultrasonic blade causes a crack to propagate in
      a controlled mode 1 opening, and these are validated against experimental data
      from three point bend fracture tests and ultrasonic cutting experiments on the
      materials. Subsequently, the finite element model is developed to represent
      ultrasonic cutting of a multi-layered material. Materials are chosen whose
      properties allow a model to be developed that could represent a multi-layer food
      product or biological structure, to enable ultrasonic cutting systems to be
      designed for applications both in the field of food processing and surgical
      procedures. The model incorporates an estimation of the friction condition
      between the cutting blade and the material to be cut and allows adjustment of the
      frequency, cutting amplitude and cutting speed.

PMID- 16814352
TI  - FE simulation of laser generated surface acoustic wave propagation in skin.
AB  - Advances in laser ultrasonics have opened new possibilities in medical
      applications, such as the characterization of skin properties. This paper
      describes the development of a multilayered finite element model (FEM) using
      ANSYS to simulate the propagation of laser generated thermoelastic surface
      acoustic waves (SAWs) through skin and to generate signals one would expect to
      observe without causing thermal damage to skin. A transient thermal analysis is
      developed to simulate the thermal effect of the laser source penetrating into the
      skin. The results from the thermal analysis are subsequently applied as a load to
      the structural analysis where the out-of-plane displacement responses are
      analysed in models with varying dermis layer thickness.

PMID- 16814353
TI  - Study of the invar effect through ultrasonic measurements of the elastic
      properties of Fe(64)Ni(36) under pressure.
AB  - The elastic properties of a polycrystalline sample of invar Fe(64)Ni(36) have
      been investigated at ambient temperature by ultrasonic experiments up to 7 GPa.
      The pressure dependence of the bulk modulus is extracted without using any model
      and discussed in terms of invar anomaly models.

PMID- 16814354
TI  - Gene expression profiles reveal an upregulation of E2F and downregulation of
      interferon targets by HPV18 but no changes between keratinocytes with integrated
      or episomal viral genomes.
AB  - Persistent infections with human papillomaviruses type 18 can result in the
      development of cervical cancer. HPV18 genomes persist extrachromosomally in low
      grade and precancerous lesions but are always integrated in cervical cancers, and
      this might contribute to the progression of HPV18-induced lesions. To address
      whether integration induces additional changes in host cells, several
      keratinocyte lines with wild type and replication-deficient E1 mutant HPV18 (E1C
      TTL) genomes were analyzed with high density oligonucleotide arrays. In
      comparison to normal keratinocytes, wild type and integrated E1C-TTL HPV18
      genomes deregulate the expression of 280 annotated genes. However, the comparison
      of wild type with E1C-TTL cell lines did not reveal any significant differences,
      indicating that neither the loss of E1 nor viral integration induces additional
      gene expression changes in low passage HPV18-positive keratinocytes. Half of the
      deregulated genes have been described as targets of the p16/Rb/E2F, p53,
      interferon or NFkappaB pathways consistent with the functions ascribed to the
      viral E6 and E7 oncoproteins, but the other half can currently not be ascribed to
      certain pathways.

PMID- 16814355
TI  - A chimeric tetravalent dengue DNA vaccine elicits neutralizing antibody to all
      four virus serotypes in rhesus macaques.
AB  - DNA shuffling and screening technologies were used to produce chimeric DNA
      constructs expressing antigens that shared epitopes from all four dengue
      serotypes. Three shuffled constructs (sA, sB and sC) were evaluated in the rhesus
      macaque model. Constructs sA and sC expressed pre-membrane and envelope genes,
      whereas construct sB expressed only the ectodomain of envelope protein. Five of
      six, and four of six animals vaccinated with sA and sC, respectively, developed
      antibodies that neutralized all 4 dengue serotypes in vitro. Four of six animals
      vaccinated with construct sB developed neutralizing antibodies against 3
      serotypes (den-1, -2 and -3). When challenged with live dengue-1 or dengue-2
      virus, partial protection against dengue-1 was observed. These results
      demonstrate the utility of DNA shuffling as an attractive tool to create
      tetravalent chimeric dengue DNA vaccine constructs, as well as a need to find
      ways to improve the immune responses elicited by DNA vaccines in general.

PMID- 16814356
TI  - Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV
      multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal
      challenge: role of SIV-specific CD8+ T cell responses.
AB  - Previously, priming with replication-competent adenovirus-SIV multigenic vaccines
      and boosting with envelope subunits strongly protected 39% of rhesus macaques
      against rectal SIV(mac251) challenge. To evaluate protection durability, eleven
      of the protected and two SIV-infected unimmunized macaques that controlled
      viremia were re-challenged rectally with SIV(mac251). Strong protection was
      observed in 8/11 vaccinees, including two exhibiting <50 SIV RNA copies.
      Decreased viremia compared to naive controls was observed in the other three. The
      SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4
      counts < or =200, unlike the protected macaques. Durable protection was
      associated with significantly increased SIV-specific ELISPOT responses and
      lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8
      re-challenged, protected vaccinees maintained <50 SIV RNA copies; SIV RNA emerged
      in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular
      immunity coincided with viremia suppression. Overall, cellular immunity induced
      by vaccination and/or low-level, inapparent viremia post-first SIV(mac251)
      challenge, was associated with durable protection against re-challenge.

PMID- 16814357
TI  - In vitro replication capacity of HIV-2 variants from long-term aviremic
      individuals.
AB  - To establish whether efficient suppression of virus replication in HIV-2-infected
      individuals is associated with low replicative capacity of HIV-2, replication
      kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and
      compared with that of the relatively slow-replicating HIV-1 variants from
      asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from
      aviremic individuals had lower replication rates than HIV-1 variants from AS/LTNP
      in cells of 8 donors (0.45 log10 [range 0.14-0.77] vs. 0.58 log10 [range 0.32
      0.99] pg RT/ml/day, P = 0.036). The relatively low replication rate of HIV-2
      compared to HIV-1 variants was not related to different sensitivities to
      inhibition by CD8+ T cells or different degrees of infectivity. HIV-2 replication
      rates increased with progressive infection and with switch from CCR5 to CXCR4
      usage. The relatively low replicative capacity of HIV-2 variants from aviremic
      individuals likely contributes to the low viral load and benign course of
      infection in these individuals.

PMID- 16814358
TI  - Laboratory investigation of the phosphorus removal (SRP and TP) from eutrophic
      lake water treated with aluminium.
AB  - Mechanisms involved in phosphorus (P) removal from eutrophic lake water with
      aluminium (Al) were assessed by jar tests. For this purpose, eutrophic lake water
      enriched with soluble reactive phosphorus (SRP), algae or sediments in order to
      mimic the various conditions found in shallow eutrophic lakes was studied. Total
      phosphorus (TP) removal was reached after floc settling, the maximal TP removal
      efficiency (90-95%) was obtained for an Al concentration ranging from 2 to 5 mg
      L(-1), depending on the organic matter (OM) origin (algae or sediments). Algae
      appeared to limit macro-floc formation (those able to settle). In contrast, in
      the presence of sediments, macro-floc formation was favoured at low Al dose (2-3
      mg L(-1) Al). High SRP removal was obtained with the lowest Al dose (1 mg L(-1)
      Al) and remained greater than 60% for an SRP concentration up to 350 microg L(
      1). SRP removal was not influenced by the OM origin. The experimental data and
      literature were used to suggest a hypothetical model for floc formation and P
      removal with Al under the conditions observed in treated lakes.

PMID- 16814359
TI  - Visualization of active biomass distribution in a BGAC fluidized bed reactor
      using GFP tagged Pseudomonas putida F1.
AB  - A favorable microenvironment for biofilm growth on GAC particles was shown using
      green fluorescent protein (GFP) as a marker for a phenol degrading bacterium,
      Pseudomonas putida F1. The dispersion of P. putida F1 in a biofilm covering
      granulated activated carbon (GAC) particles was monitored and compared to a
      biofilm on non-activated granular carbon particles. Laser scanning confocal
      microscopy (LSCM) micrographs of the biofilms taken from two fluidized bed
      reactors operating under identical conditions, showed higher fluorescent green
      areas in the GAC biofilm, especially close to the GAC surface. Quantitative
      analysis of the biofilm by COMSTAT, a three-dimensional biofilm structure
      analysis program, showed higher biomass concentration and higher viability in the
      GAC covered biofilm vs. the non-activated carbon biofilm. In addition, better
      effluent quality was measured for the BGAC reactor, which strongly suggests a
      significantly larger biofilm surface area available to the substrate, as opposed
      to that of the non-activated carbon carrier reactor.

PMID- 16814360
TI  - Microbial sulfate reduction under sequentially acidic conditions in an upflow
      anaerobic packed bed bioreactor.
AB  - The aim of this study was to operate an upflow anaerobic packed bed reactor
      (UAPB) containing sulfate reducing bacteria (SRB) under acidic conditions similar
      to those found in acid mine drainage (AMD). The UAPB was filled with sand and
      operated under continuous flow at progressively lower pH and was shown to be
      capable of supporting sulfate reduction at pH values of 6.0, 5.0, 4.5, 4.0 and
      3.5 in a synthetic medium containing 53.5 mmol l(-1) lactate. Sulfate reduction
      rates of 553-1,052 mmol m(-3) d(-1) were obtained when the influent solution pH
      was progressively lowered from pH 6.0 to 4.0, under an optimal flow rate of 2.61
      ml min(-1). When the influent pH was further lowered to pH 3.5, sulfate reduction
      was substantially reduced with only about 1% sulfate removed at a rate of 3.35
      mmol m(-3) d(-1) after 20 days of operation. However, viable SRB were recovered
      from the column, indicating that the SRB population was capable of surviving and
      metabolizing at low levels even at pH 3.5 conditions for at least 20 days. The
      changes in conductivity in the SRB column did not always occur with changes in pH
      and redox potential, suggesting that conductivity measurements may be more
      sensitive to SRB activity and could be used as an additional tool for monitoring
      SRB activity. The bioreactor containing SRB was able to reduce sulfate and
      generate alkalinity even when challenged with influent as low as pH 3.5,
      indicating that such treatment systems have potential for bioremediating highly
      acidic, sulfate contaminated waste waters.

PMID- 16814361
TI  - The potential of producing heterotrophic bacteria biomass on aquaculture waste.
AB  - The effluent from the drumfilter of a recirculation aquaculture system was used
      as substrate to produce heterotrophic bacteria in suspended growth reactors. The
      effects of organic carbon supplementation (0, 3, 6, 8 g/l sodium acetate) and of
      hydraulic retention times (11-1h) on bacteria biomass production and nutrient
      conversion were investigated. Bacteria production, expressed as volatile
      suspended solids (VSS), was enhanced by organic carbon supplementation, resulting
      in a production of 55-125 g VSS/kg fish feed (0.2-0.5 g VSS/g carbon). Maximum
      observed crude protein production was approximately 100 g protein/kg fish feed.
      The metabolic maintenance costs were 0.08 Cmol/Cmol h, and the maximum growth
      rate was 0.25-0.5 h(-1). Ninety percent of the inorganic nitrogenous and 80% of
      ortho-phosphate were converted. Producing bacteria on the drumfilter effluent
      results in additional protein retention and lowers overall nutrient discharge
      from recirculation aquaculture systems.

PMID- 16814362
TI  - Effect of precursor concentration on the characteristics of nanoscale zerovalent
      iron and its reactivity of nitrate.
AB  - Differing precursor concentrations, 1.0, 0.1, and 0.01 M FeCl(3) x 6H(2)O, were
      performed to produce nanoscale Fe(0) and the results were discussed in terms of
      the specific surface area, particle size and electrochemical properties. The
      results indicated that the nanoscale Fe(0) prepared by 0.01 M FeCl(3) had
      absolutely reduced in size (9-10nm) and possessed the greatest specific surface
      area (56.67 m(2) g(-1)). These synthesized nanoscale Fe(0) particles were
      attempted to enhance the removal of 40 mg-NL(-1) unbuffered nitrate solution. The
      first-order degradation rate constants (k(obs)) increased significantly (5.5-8.6
      times) with nanoscale Fe(0) prepared by 0.01 M precursor solution (Fe(0.01
      M)(0)). When normalized to iron surface area concentration, the specific rate
      constant (k(SA)) was increased by a factor of approximately 1.7-2.4 using Fe(0.01
      M)(0) (6.84 x 10(-4) L min(-1) m(-2) for Fe(0.01 M)(0), 4.04 x 10(-4) L min(-1)
      m(-2) for Fe(0.1 M)(0) and 2.80 x 10(-4) L min(-1) m(-2) for Fe(1 M)(0)). The
      rise of reactivity of the reactive site on the Fe(0.01 M)(0) surface was
      indicated by the specific rate constant (k(SA)) calculation and the i(0) value of
      the electrochemical test.

PMID- 16814363
TI  - Bioavailability and mass balance studies of a commercial pentabromodiphenyl ether
      mixture in male Sprague-Dawley rats.
AB  - Polybrominated diphenyl ethers (PBDE) are common flame retardants used in
      polyurethane foam, high impact polystyrene, and textiles which appear to be
      increasing in the environment and biota. Two PBDE congeners that are particularly
      prominent in environmental samples are 2,2',4,4'-tetrabromodiphenyl ether (BDE
      47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). These two congeners are
      major components in penta-BDE formulations which constitute a minor percentage of
      the commercial PBDE market. In order to determine the bioavailability and
      bioconcentration potential of these PBDEs, we have conducted a feeding experiment
      in rats, dosing with low amounts of a commercial penta-BDE mixture for 21 days to
      mimic an environmental exposure. The carcasses, livers, and feces from control
      and dosed rats were quantitated for PBDEs by a high resolution GC-MS isotope
      dilution method. Between 25% and 50% of each of the dosed congeners was retained
      in the rats with the liver being a minor depot (<1% of the dose). Fecal excretion
      accounted for 4-12% of the dosed congeners. A large percent of the dose (40-60%)
      was not recovered indicating that metabolic transformations may have occurred in
      the rats. Hydroxylated metabolites were qualitatively identified in the feces and
      carcass by GC-MS. The relative congener distribution in each tissue was nearly
      identical to the congener distribution of the commercial mixture. Conclusions
      from the study suggest that the tetra- to hexa-BDEs present in commercial penta
      BDE formulations are largely bioavailable, that bioavailability in the rat is not
      dependent on the degree of bromination, and that metabolism may occur to a large
      extent during a chronic exposure.

PMID- 16814364
TI  - Mercury levels in sediments of central Mediterranean Sea: a 150+ year record from
      box-cores recovered in the Strait of Sicily.
AB  - To evaluate the degree of anthropogenic mercury pollution, Hg contents have been
      measured for box-core sediments sampled along three nearshore-offshore transects
      in the Strait of Sicily and well constrained for their mineralogy, bulk
      geochemistry and TOC%. Hg values are generally low (from 15 to 70 microg kg(-1));
      however, depth profiles clearly display upcore rising concentrations (up to 202
      microg kg(-1) near the SE Sicily coast) that are attributed to anthropogenic
      load. Based on (210)Pb chronology, these trends are more dramatic across the last
      20-30 years. Geogenic influence is thought to explain some anomalies related to
      volcanic emission and geothermal activity. Combined effects due to eastward
      flowing of the Modified Atlantic Water (MAW) and sea bottom morphology drove
      major anthropogenic accumulation.

PMID- 16814365
TI  - Heterogeneous photocatalytic decomposition of benzene on lanthanum-doped TiO2
      film at ambient temperature.
AB  - Lanthanum-doped anatase TiO2 thin films on glass prepared via a sol-gel process
      have been shown to have much higher photocatalytic activity for the degradation
      of gaseous benzene than pure anatase TiO2 thin film. The photodecomposition of
      benzene on both types of TiO2 films follows the first-order kinetics while the
      CO(2) and CO formation followed the zero-order kinetics. GC/MS identification of
      the intermediates produced during the photodegradation of benzene revealed that
      doping lanthanum into TiO2 thin film favors a cleavage of benzene ring. An
      optimal lanthanum amount with respect to photocatalytic activity was about 2.5
      wt% (La2O3/TiO2).

PMID- 16814366
TI  - Mobilisation and attenuation of boron during coal mine rehabilitation, Wangaloa,
      New Zealand.
AB  - Environmental mobility and fate of boron has been traced from source to discharge
      waters through the rehabilitated Wangaloa coal mine in southern New Zealand. The
      boron is derived initially from coal, which has up to 450 mg/kg B. The coal also
      contains pyrite (2-5 wt.% S), which oxidizes to yield a low-pH environment
      (typical pH 2-5). Weathering of coal-bearing waste rock liberates B into
      rainwater that infiltrates into waste rock or evaporates to leave a gypsum crust
      enriched in B, possibly as boric acid or colemanite as inferred from geochemical
      modelling. Surface waters dissolve this evaporative material periodically,
      yielding total B concentrations up to 6 mg/L, at pH<4.5. Some of the available B
      is taken up by plants that have been established on the waste rock, resulting in
      foliage B concentrations of up to 230 mg/kg (dry weight). Partial attenuation of
      dissolved B by adsorption to iron oxyhydroxide occurs as groundwater passes
      through waste rock, but this is inhibited by adsorption competition with
      dissolved sulphate (up to 600 mg/L). Groundwater flows from the mine through a
      pit lake and wetland, with total dissolved B near 1 mg/kg after dilution and
      limited adsorption attenuation has occurred. Despite the widespread B mobility
      throughout the rehabilitated mine, there is little evidence of B toxicity in
      plants. The B concentrations in discharging waters are in the environmentally
      safe range for most aquatic organisms, being neither deficient in B as a
      micronutrient, nor boron-toxic.

PMID- 16814367
TI  - Reducing PCDD/F formation by adding sulfur as inhibitor in waste incineration
      processes.
AB  - The results obtained in this study indicate that addition of sulfur in
      incineration processes could effectively reduce PCDD/F formation. PCDD/F
      formation is reduced dramatically (54.1%) when S/Cl molar ratio is controlled at
      about 2 in a laboratory-scale system (LSS). The XRD analysis of the fly ash
      confirms the existence of vulcanized metals such as Cu2SO4, Cu2S, SnS and ZnS.
      The results suggest that the sulfur added would poison Cu-based metals and render
      the Deacon reaction catalyst less active, thereby reducing PCDD/F formation. In
      addition, the results obtained from the tests conducted in an industrial waste
      incinerator (IWI) indicate that the efficiency of reducing PCDD/F formation by
      adding sulfur was 51.6% at S/Cl mole ratio of 0.4. The results indicate that
      adding too much sulfur would actually increase particle concentration and also
      increase PCDD/F yield. This study demonstrates the effectiveness of adding sulfur
      as an alternative technology for reducing PCDD/F emissions from waste
      incineration processes. The efficiency of reducing PCDD/F formation by addition
      of sulfur is strongly influenced by S/Cl mole ratio.

PMID- 16814368
TI  - Anthropogenic nitrogen input traced by means of delta15N values in macroalgae:
      results from in-situ incubation experiments.
AB  - The macroalgae species Fucus vesiculosus (Phaeophyta), Polysiphonia sp., and
      Ceramium rubrum (Rhodophyta) originally grown at an unpolluted brackish site of
      the southern Baltic Sea were incubated for 10 and 14 days at 12 stations along a
      salinity gradient in a highly polluted estuary. We have expected an adaptation of
      the initially low delta15N values to the higher ones within the incubation
      period. In addition to the macroalgae the delta15N values of NO3(-) were measured
      to evaluate fractionation processes of the source nitrate. Inside the estuary,
      delta15N-NO3(-) values were 6.2-9.7 per thousand, indicating anthropogenic
      nitrogen sources. The red macroalgae adequately reflected the nitrate isotope
      values in the surrounding waters, whereas for F. vesiculosus the results were not
      that clear. The reasons were assumed to be higher initial delta15N values of F.
      vesiculosus and presumably a too slow nitrogen uptake and growth rate. The method
      of macroalgae incubations seems suitable as a simple monitoring to study the
      influence of anthropogenic nitrogen loading in an estuarine environment.

PMID- 16814369
TI  - Metabolic regulation and chemotherapy.

PMID- 16814370
TI  - Participation of the general gynecologist in surgical staging of endometrial
      cancer: analysis of cost and perioperative outcomes.
AB  - OBJECTIVE: To compare the cost and perioperative outcomes of endometrial cancer
      staging when the procedure is performed by a gynecologic oncologist alone or when
      a general gynecologist participates in the procedure. METHODS: A retrospective
      analysis was performed on a series of women with clinical stage I endometrial
      cancer treated at a single institution between 1/98 and 12/00. The patients were
      grouped according to the participation of a general gynecologist in their
      surgery. The 48 patients in Group 1 underwent surgery with a general gynecologist
      who consulted a gynecologic oncologist intraoperatively. Group 2 included 77
      patients whose procedure was performed completely by a gynecologic oncologist.
      The two groups were compared with the chi-square, Fisher's exact, and Wilcoxon
      rank sum tests. Cost analysis included total hospital costs (room, pharmacy, and
      ancillary services) and total surgical costs (anesthesia, operating room,
      procedure, and perioperative physician evaluation costs). RESULTS: The groups did
      not differ in age, type of surgeries performed, distribution of surgical stage,
      proportion of patients undergoing lymph node sampling (LNS), and length of follow
      up. When LNS was performed, Group 2 had a significantly shorter median operative
      time (170 vs. 180 min; P=0.05) and shorter total time in the operating room (204
      vs. 224 min; P=0.02). This group had a lower procedure cost when considered both
      in terms of payor's cost ($1,414 vs. $2,134; P<0.0001) and physician charge
      ($7,106 vs. $11,116; P<0.0001). Perioperative physician evaluation was reduced by
      almost half ($685 vs. $424; P<0.0001) in Group 2. Group 2 had a savings in total
      surgical cost by payor's cost ($9,142 vs. 10,294; P=0.005) or physician's charge
      ($14,546 vs. $19,276; P<0.0001), and in combined hospital and surgical cost by
      payor's cost ($15,664 vs. $17,346; P=0.004) or physician charge ($21,311 vs.
      $26,328; P<0.0001). Total hospital costs, however, did not differ between groups.
      CONCLUSION: Operative time and costs increase when general gynecologists
      participate in the surgical procedure of patients with clinical stage I
      endometrial cancer. Although perioperative outcomes are similar, the involvement
      of two surgeons increases the length of the procedure as well as the cost of
      operating room time and physician reimbursement. The efficient use of limited
      health care resources must be considered as we plan the surgical approach to
      endometrial cancer.

PMID- 16814371
TI  - Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by
      consolidation chemotherapy for women with locally advanced carcinoma of the
      uterine cervix--final results of a prospective phase II-study.
AB  - OBJECTIVES: To evaluate the efficacy and toxicity of ifosfamide and cisplatin
      administered concomitantly with low-dose rate brachyradiotherapy followed by
      consolidation chemotherapy in the treatment of locally advanced squamous cell
      carcinoma (LASCC) or adeno/adenosquamous carcinoma of the uterine cervix.
      METHODS: Sixty-two patients with primary uterine cervical cancer were enrolled
      between August 1999 and November 2004. The patients had to have FIGO-stage IB2
      bulky to IVA disease, biopsy-proven squamous cell or adeno/adenosquamous
      carcinoma of the uterine cervix. The patients were to receive external
      radiotherapy (50 Gy in 25 fractions); ifosfamide 2 g/m2 plus cisplatin 75 mg/m2
      was applied concomitantly during two low-dose rate brachyradiotherapy
      applications; the planned dose to point A was 85 Gy in total. After the
      completion of radiotherapy, i.e. external and concomitant
      chemobrachyradiotherapy, four cycles of consolidation chemotherapy with the same
      drug combination were to be administered. RESULTS: The clinical complete response
      rate according to WHO-classification (assessed after the completion of the whole
      treatment procedures by gynecologic and radiologic evaluation and cervical
      biopsy) was 100%. After a median follow-up of 49 months (range 11-74 months), the
      recurrence-free and overall survival rates were 88.7%, respectively. The most
      frequent early toxicities were grade 3 and 4 leukopenias occurring in 25% and 11%
      of the cycles, respectively. Major delayed local complications occurred in 10
      patients (16.1%). CONCLUSION: These results indicate that concomitant
      chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation
      chemotherapy with the same drug combination is a highly efficacious and very
      promising treatment protocol for patients with locally advanced LASCC or
      adeno/adenosquamous carcinoma of the uterine cervix.

PMID- 16814372
TI  - Effects of genetically altered brain glucocorticoid receptor action on behavior
      and adrenal axis regulation in mice.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with
      vulnerability to a number of psychiatric diseases including major depression,
      bipolar disorder, anxiety disorders, and schizophrenia. The HPA axis is activated
      in response to stress and in a characteristic circadian rhythm, resulting in the
      release of glucocorticoid hormones from the adrenal cortex. These hormones act on
      peripheral target tissues to restore homeostasis to the organism and engage
      glucocorticoid receptors (GR) in the CNS to control the intensity and duration of
      the stress response. Alterations in this glucocorticoid sensing system may
      underlie the HPA axis changes associated with psychiatric disorders. Recently, a
      number of lines of mice with genetically altered GR signaling in the CNS have
      been generated to address this hypothesis. Here, we summarize findings from new
      genetic models that indicate a critical role for GR signaling in the CNS in
      normal regulation of the HPA axis and behavioral/emotional stability.

PMID- 16814373
TI  - Central effects of the anabolic steroid 17alpha methyltestosterone in female
      anxiety.
AB  - The androgen 17alpha-methyltestosterone (17alpha-meT) is one of the most commonly
      abused anabolic androgenic steroids (AAS). We assessed the impact of 17alpha-meT
      after bilateral infusion into the dorsomedial hypothalamus (DMH) in female
      anxiety. A paradoxical effect in Vogel conflict test (VCT) behavior was noted:
      while AAS infusion induced an increase in the latency to display the appetitive
      reaction of the task, it also increased the number of punished responses. No
      changes in elevated plus maze (EPM) behavior were noted. However, AAS infusion
      induced an increase in social interactions. Changes in social interactions were
      mimicked by muscimol infusion and counteracted by co-infusion of AAS plus the
      GABAA receptor (GABAA-R) antagonist GABAzine. A reduction of systolic blood
      pressure was registered after AAS infusion in the DMH. No changes in fluid intake
      or locomotor behaviors were noted. We conclude that the AAS 17alpha-meT modulates
      distinct anxiety domains in females through a fast-acting mechanism.

PMID- 16814374
TI  - The cannabinoid CB1 receptor inverse agonist, rimonabant, modifies body weight
      and adiponectin function in diet-induced obese rats as a consequence of reduced
      food intake.
AB  - The cannabinoid CB1 receptor inverse agonist rimonabant induces hypophagia and
      body weight loss. Reduced body weight may potentially be due to decreased food
      intake or to direct metabolic effects of drug administration on energy
      expenditure. This study uses a paired-feeding protocol to quantify the
      contributions of energy intake to rimonabant-induced body weight loss. Diet
      induced obese (DIO) rats were dosed with rimonabant (3, 10 mg/kg PO once daily)
      and matched with pair-fed controls. Food intake and body weight were measured
      daily. Blood samples and adipose tissue were collected on day 15 for measurement
      of plasma adiponectin and adiponectin mRNA levels. DIO rats treated with
      rimonabant and pair-fed controls showed very similar changes in body weight.
      Although tolerance developed to the anorectic effect of rimonabant, total food
      intake was significantly decreased over the 14-day study period and fully
      accounted for the observed reductions in body weight. Adiponectin mRNA and plasma
      adiponectin were elevated in vehicle-treated chow-fed animals compared to obese
      controls, and did not differ between rimonabant-treated and pair-fed animals. The
      similarities between rimonabant-treated and pair-fed animals in body weight loss
      and the absence of differences in measures of adiponectin activity between drug
      treated and pair-fed animals suggest that the outcomes of this experiment were
      solely mediated by the drug-induced reduction in food intake.

PMID- 16814375
TI  - Viability and DNA fragmentation in differently sorted boar spermatozoa.
AB  - Sperm cell defense against DNA damage relies on two factors: the tight packaging
      of chromatin, based on condensation and substitution of histones with protamines,
      and the antioxidant agents present in seminal plasma. These defenses are
      extremely important as mature sperm is unable to repair DNA damage and even if a
      successful fertilization occurs, embryo undergoes apoptosis at the time of
      genomic activation. Sex-sorting exposes spermatozoa to stress sources such as
      high pressure, laser beam and electrical charge. The aim of this work was to
      determine how sorting procedures affect viability and DNA integrity in boar
      spermatozoa, by using the newly developed Sperm-Sus-Halomax. Four sperm
      populations were considered: CONTROL (no treatment), REAL (sex-sorted semen),
      BULK (semen sorted without sex separation) and NO LASER (semen only exposed to
      the high pressure, but including also cells normally discarded from sex-sorting).
      A significantly (P=0.019) lower viability in NO LASER (64.71%) than in CONTROL
      (78.6%) and REAL (80.5%) groups was found; this was accompanied by a
      significantly (P=0.001) higher DNA fragmentation index (DFI) in NO LASER group
      (6.86%) respect to CONTROL (3.30%) and REAL (3.42%) groups. BULK group did not
      show any difference in viability or DFI as compared to the other groups. In
      conclusion, we may believe that sex-sorting procedure as a whole does not affect
      either viability or DFI and that shear mechanical forces are a relevant source of
      DNA damage for sorted semen.

PMID- 16814376
TI  - Nonword repetition skills in young children who do and do not stutter.
AB  - The purpose of this study was to assess the nonword repetition skills of 24
      children who do (CWS; n = 12) and do not stutter (CWNS; n = 12) between the ages
      of 3;0 and 5;2. Findings revealed that CWS produced significantly fewer correct
      two- and three-syllable nonword repetitions and made significantly more phoneme
      errors on three-syllable nonwords relative to CWNS. In addition, there was a
      significant relationship between performance on a test of expressive phonology
      and nonword repetition for CWS, but not CWNS. Findings further revealed no
      significant fluctuation in fluency as nonwords increased in length. Taken
      together, findings lend support to previous work, suggesting that nonword
      repetition skills differ for CWS compared with CWNS, and that these findings
      cannot be attributed to (a) weak language performance on the part of CWS, or (b)
      the occurrence of stuttering in the course of nonword production. EDUCATIONAL
      OBJECTIVES: After reading this article, the learner will be able to: (a) describe
      one common means of assessing phonological working memory in children; (b)
      summarize the performance differences of children who stutter compared to peers
      on a nonword repetition task; (c) compare the results of the present study with
      previous work in this area.

PMID- 16814377
TI  - Kinetics of Cd accumulation and elimination in tissues of juvenile rockfish
      (Sebastes schlegeli) exposed to dietary Cd.
AB  - Cadmium (Cd) accumulation and elimination were investigated in the tissues (gill,
      intestine, kidney, lever and muscle) of juvenile rockfish, Sebastes schlegeli,
      after sub-chronic dietary Cd exposure (0, 0.5, 5, 25 and 125 mg/kg). No mortality
      occurred during the sub-chronic exposure to dietary Cd. Specific growth rates of
      the rockfish estimated by weight and length were significantly different from
      those of the control, and a significant inverse relationship was observed between
      weight gain and the exposure concentration of dietary Cd at 25, 125 mg/kg. Cd
      accumulation in the tissues increased with exposure periods and concentrations
      for the 60 days of dietary Cd exposure. Cd accumulation in the intestine of
      rockfish was higher than other tissues, and the order of Cd accumulation in
      tissues were intestine>kidney approximately liver>gill>muscle. Accumulation
      factors showed an increase with the exposure period and an inverse relationship
      between the accumulation factor and the exposure concentrations in the gill,
      intestine, liver and muscle, but not in kidney. Cd elimination in tissues of
      rockfish decreased during the 30 days of depuration except kidney and muscle.
      Intestine showed the fastest elimination rates of Cd at all concentrations
      compared with other tissues.

PMID- 16814378
TI  - Association between UHMWPE particle-induced inflammatory osteoclastogenesis and
      expression of RANKL, VEGF, and Flt-1 in vivo.
AB  - Wear debris-induced vascularized granulomatous periprosthetic tissue may augment
      the progress of prosthetic loosening, a major clinical problem after total joint
      replacement. The purpose of this study is to investigate the association of ultra
      high-molecular-weight polyethylene (UHMWPE) particle-induced inflammatory
      osteoclastogenesis and expression of RANK/RANKL and VEGF/VEGF receptors (Flt-1
      and Flk-1) using a mouse osteolysis model. UHMWPE particles were introduced into
      established air pouches on BALB/c mice, followed by implantation of calvaria bone
      from syngeneic littermates. Mice were injected with either recombinant VEGF or
      VEGF inhibitor (VEGF R2/F(c) Chimera). Mice without drug treatment, as well as
      mice injected with saline alone were included. Each group contains 10 mice. Pouch
      tissues were harvested 2 weeks after bone implantation for histological and
      molecular analysis. UHMWPE stimulation significantly increased VEGF gene
      expression, and exerted a lower enhancement effect on the gene expression of Flt
      1 and Flk-1. UHMWPE-stimulated VEGF production was markedly reduced by VEGF
      inhibitor treatment. Immunofluorescent staining indicated that pouch tissue
      macrophages were the main source of both VEGF and Flt-1 production. A positive
      association was observed between tissue inflammation and the levels of VEGF and
      Flt-1 gene transcripts. Both RANK and RANKL gene transcripts were significantly
      increased by UHMWPE stimulation, which was subsequently reduced by VEGF inhibitor
      treatment (p<0.05). VEGF treatment increased TRAP(+) cells in pouches either with
      or without UHMWPE particle stimulation, and VEGF inhibitor treatment caused a
      significant reduction in the number of TRAP(+) cells in UHMWPE-containing
      pouches. This study suggests that VEGF has a role in the regulation of RANK/RANKL
      mediated osteoclastogenesis, and warrant future investigations to elucidate the
      role of VEGF signaling in the pathogenesis of prosthetic loosening.

PMID- 16814380
TI  - Orphan neuropeptides. Novel neuropeptides modulating sleep or feeding.
AB  - Neuropeptides form the largest family of modulators of synaptic transmission.
      Until 1995 some 60 different neuropeptides had been found. With the recognition
      that all neuropeptides act by binding to G protein coupled receptors (GPCRs), a
      new approach relying on the use of orphan GPCRs as targets was designed to
      identify novel neuropeptides. Thirteen new neuropeptide families have since been
      discovered. In this review we will describe the orphan GPCR-based approach that
      led to these discoveries and present its impact on two specific physiological
      responses, feeding and sleep. In particular, we will discuss the modulatory roles
      of the hypocretins/orexins and of neuropeptide S in sleep and awakening and those
      of ghrelin and melanin concentrating hormone in food intake.

PMID- 16814379
TI  - Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils.
AB  - The S100 family member S100A9 and its heterodimeric partner, S100A8, are
      cytosolic Ca2+ binding proteins abundantly expressed in neutrophils. To
      understand the role of this EF-hand-containing complex in Ca2+ signalling,
      neutrophils from S100A9 null mice were investigated. There was no role for the
      complex in buffering acute cytosolic Ca2+ elevations. However, Ca2+ responses to
      inflammatory agents such as chemokines MIP-2 and KC and other agonists are
      altered. For S100A9 null neutrophils, signalling at the level of G proteins is
      normal, as is release of Ca2+ from the IP(3) receptor-gated intracellular stores.
      However MIP-2 and FMLP signalling in S100A9 null neutrophils was less susceptible
      than wildtype to PLCbeta inhibition, revealing dis-regulation of the signalling
      pathway at this level. Downstream of PLCbeta, there was reduced intracellular
      Ca2+ release induced by sub-maximal levels of chemokines. Conversely the response
      to FMLP was uncompromised, demonstrating different regulation compared to MIP-2
      stimulation. Study of the activity of PLC product DAG revealed that chemokine
      induced signalling was susceptible to inhibition by elevated DAG with S100A9 null
      cells showing enhanced inhibition by DAG. This study defines a lesion in S100A9
      null neutrophils associated with inflammatory agonist-induced IP3-mediated Ca2+
      release that is manifested at the level of PLCbeta.

PMID- 16814381
TI  - Trisomy 8 as sole anomaly or with other clonal aberrations in acute myeloid
      leukemia: impact on clinical presentation and outcome.
AB  - One hundred and fifty-four acute myeloid leukemia patients with trisomy 8 were
      studied for their clinical and biological characteristics, and treatment outcome.
      Forty-seven patients presented with trisomy 8 as the sole aberration, 107 with
      trisomy 8 associated with other cytogenetic abnormalities (13 with favorable, 54
      with intermediate, and 40 with unfavorable risk cytogenetics). Overall complete
      remission (CR) proportion was 48%. Median disease-free survival (DFS) and overall
      survival (OS) were 7.8 and 8.3 months, respectively. In multivariate analysis,
      age >or=60 years (P<0.0001) and association with unfavorable karyotype (P=0.03)
      were of poor prognostic value for CR achievement. Age >or=60 years (P<0.0001) and
      antecedents of dysmyelopoiesis (P=0.02) were of poor prognostic value for OS.
      Patients with trisomy 8 alone did not show any difference in terms of outcome as
      compared with those in whom trisomy 8 was associated to intermediate risk
      cytogenetics (P=0.0002). Trisomy 8 in addition to favorable karyotype maintained
      a good clinical outcome, while trisomy 8 in addition to unfavorable cytogenetics
      showed the worst prognosis.

PMID- 16814382
TI  - A mathematical model for the evaluation of amplitude of hemoglobin fluctuations
      in elderly anemic patients affected by myelodysplastic syndromes: correlation
      with quality of life and fatigue.
AB  - Therapy with RBC transfusions and rHuEPO for management of anemia in patients
      with myelodysplastic syndromes causes recurrent fluctuations in hemoglobin
      levels. The purpose of this study was to elaborate a mathematical model for the
      interpretation of hemoglobin fluctuations and to correlate the resulting
      numerical parameter (Variaglobin Index) with quality of life and fatigue. In 32
      myelodysplastic patients, lower amplitude of the Variaglobin Index was found
      significantly correlated with a better quality of life and less fatigue. The
      mathematical model proposed here makes it easy to monitor anemia in
      myelodysplastic patients and to adjust therapy accordingly.

PMID- 16814383
TI  - Temperature modifies gene expression in subcuticular epithelial cells of white
      spot syndrome virus-infected Litopenaeus vannamei.
AB  - Subtractive suppressive hybridization was used to identify differentially
      expressed genes in subcuticular tissues from white spot syndrome virus(WSSV)
      infected shrimp kept at different temperatures. Subtractive libraries I and II
      contained genes expressed at 26 and 33 degrees C, respectively. Three hundred and
      seventy-nine insert positive clones were selected to confirm differential
      expression by dot-blot hybridization. Twenty-two clones from library I and eight
      from library II were sequenced. All sequences from Library I corresponded to
      white spot syndrome virus genes. From library II, five clones were homologous
      with previously reported expressed sequence tags of Litopenaeus vannamei, two had
      similarity with beta-actin and one transcript represented an unknown gene. Over
      expression of VP15 in shrimp at 26 degrees C was further confirmed by real-time
      polymerase chain reaction (PCR), whereas beta-actin expression was similar in
      animals kept at both temperatures. Together, our results show that hyperthermia
      reduces the expression of WSSV genes on shrimp subcuticular epithelial cells.

PMID- 16814384
TI  - Toxicity study of maternal transfer of polychlorinated biphenyls and diethyl
      phthalate to 21-day-old male and female weanling pups of Wistar rats.
AB  - Polychlorinated biphenyls (PCBs) are environmental pollutants known to act as
      xenoestrogens. PCBs and diethylphthalate (DEP) are ubiquitous environmental
      pollutants because both are used as plasticizers and in various other industrial
      applications. Therefore, a study was undertaken to evaluate the interactive
      toxicity of DEP and PCB in 21-day-old male and female pups of Wistar rats.
      Healthy young male and female albino rats of Wistar strain weighing 75-100g (6-7
      weeks old) were randomly assigned to four groups of six each. Group I male and
      female rats were fed a normal diet and water ad libitum. Group II and III male
      and female rats were given PCB (Clophen A60) and DEP dissolved in corn oil mixed
      with the diet at 50 mg/kg of the diet (2.85 mg/kg body wt) individually to each
      group. Group IV male and female rats received a mixture of DEP and PCB (Clophen
      A60), each dissolved in corn oil mixed with the diet at 50 mg/kg of the diet
      (2.85 mg/kg body wt). Hundred days after the treatment, females were mated with
      males for 10 days. Exposure to DEP and PCB was continued throughout mating,
      gestation until termination at weaning, which was 150 days of total treatment
      period of adults. The pups from each group were then segregated on the basis of
      their sex. Six male and female pups each (approx. 21 days old) from each group
      were chosen randomly and were killed for toxicity study. Liver-to-body weight
      ratio showed significant increase in the male and female pups of PCB- and PCB+DEP
      treated rats, whereas male pups of DEP alone treated rats showed significant
      increase and female pups showed significant decrease as compared to controls and
      other treated groups. Significant increase in liver and serum lactate
      dehydrogenase (LDH) and acid phosphatase (ACP) activity in the male and female
      pups of the three treated groups was observed. Alkaline phosphatase (ALP)
      activity was significantly increased only in the serum of male and female pups of
      the three treated groups, whereas significant decrease in the liver of male pups
      of the three treated groups. In the female pups, significant decrease in liver
      ALP was observed only PCB- and PCB+DEP-treated groups. Histology of liver showed
      severe vacuolation and steatosis in the hepatocytes of PCB-treated male and
      female pups and in PCB+DEP-treated group, vacuolation, and steatosis was much
      more predominant as compared to the PCB and DEP alone treated groups. DEP alone
      treated groups, both male and female pups showed mild vacuolations in the liver.
      A synergistic interactive toxic effect of PCB and DEP was evident in both male
      and female pups in the following study.

PMID- 16814385
TI  - Trace metal bioaccumulation: models, metabolic availability and toxicity.
AB  - Aquatic invertebrates take up and accumulate trace metals whether essential or
      non-essential, all of which have the potential to cause toxic effects. Subsequent
      tissue and body concentrations of accumulated trace metals show enormous
      variability across metals and invertebrate taxa. Accumulated metal concentrations
      are interpreted in terms of different trace metal accumulation patterns, dividing
      accumulated metals into two components - metabolically available metal and stored
      detoxified metal. Examples of different accumulation patterns are described from
      crustaceans but have a general applicability to all aquatic invertebrates.
      Toxicity does not depend on total accumulated metal concentration but is related
      to a threshold concentration of internal metabolically available metal. Toxicity
      ensues when the rate of metal uptake from all sources exceeds the combined rates
      of detoxification and excretion (if present) of the metal concerned. The
      biodynamic model of trace metal bioaccumulation allows the prediction and
      explanation of widely differing accumulated trace metal concentrations in
      organisms, combining geochemical analyses of environmental metal concentrations
      with the measurement of key physiological parameters for a species from the site
      under consideration. The combination of the biodynamic model as a unified
      explanation of metal bioaccumulation with an understanding of the relationship
      between accumulation and toxicity sets the stage for a realistic understanding of
      the significance of trace metal concentrations in aquatic invertebrates.

PMID- 16814386
TI  - Chlorinated paraffins: a review of analysis and environmental occurrence.
AB  - Chlorinated paraffins (CPs), as technical mixtures of polychlorinated alkanes
      (PCAs), are ubiquitous in the environment. CPs tend to behave in a similar way to
      persistent organic pollutants (POPs), leading several countries to impose
      regulations on the use of CPs. In this article, we review the literature on the
      properties of CPs, the current analytical tools available to determine CPs in
      various types of environmental matrices, and concentrations found in the
      environment. In particular, concentrations of CPs in environmental compartments
      including air, water, sediments, biota, human food products and human tissues are
      summarized. Priorities for future research are: improvements in analytical
      methodologies (reducing the complexity of the analysis, producing reference
      materials and performing interlaboratory studies); determining background levels
      of chlorinated paraffins in the environment and human populations (this question
      should be answered using quality assured analytical tools allowing the
      intercomparison of data); and investigating the sources of CPs to the environment
      and to humans.

PMID- 16814387
TI  - Epratuzumab, a CD22-targeting recombinant humanized antibody with a different
      mode of action from rituximab.
AB  - Epratuzumab is a humanized anti-CD22 monoclonal antibody currently in clinical
      trials for treatment of non-Hodgkin lymphoma (NHL) and certain autoimmune
      diseases. Here we report the results of investigations of epratuzumab's mode of
      action in comparison to and in combination with the anti-CD20 mAb, rituximab. In
      vitro cell growth inhibition, induction of apoptosis, and the ability of the mAbs
      to mediate complement-dependent cytotoxicity (CDC) and antibody-dependent
      cellular cytotoxicity (ADCC) were evaluated. We also investigated the potential
      activity of epratuzumab in the regulation of B-cell antigen receptor (BCR)
      activation. Epratuzumab and rituximab displayed very distinct modes of action;
      epratuzumab acts as an immunomodulatory agent, while rituximab is an acutely
      cytotoxic therapeutic antibody. Epratuzumab has distinct effects on cell growth
      from rituximab. For example, rituximab+anti-human IgG Fcgamma yielded marked
      inhibition of proliferation in human NHL cell lines, while epratuzumab had little
      or no effect in this assay. However, when cells were immobilized and stimulated
      with anti-IgM, epratuzumab, but not rituximab, caused a significant
      antiproliferative effect. Unlike rituximab, no CDC could be detected, and ADCC
      was modest but significant with epratuzumab. Importantly, combining rituximab and
      epratuzumab did not decrease rituximab's ability to induce apoptosis, CDC, and
      ADCC. In fact, the combination is more effective than rituximab alone in
      inhibiting proliferation of Daudi Burkitt lymphoma cells in the presence of
      second antibody, and at least equally effective to rituximab in the absence of
      crosslinking. These observations suggest that it may be possible to enhance
      clinical efficacy by combination therapy comprised of anti-CD20 and anti-CD22
      mAbs.

PMID- 16814388
TI  - The change of the scFv into the Fab format improves the stability and in vivo
      toxin neutralization capacity of recombinant antibodies.
AB  - The antigen-binding fragment (Fab) has been considered a more functionally stable
      version of recombinant antibodies than single chain antibody fragments (scFvs),
      however this intuitive consideration has not been sufficiently proven in vivo.
      This communication shows that three out of four specific scFvs against a scorpion
      toxin, with different affinities and stabilities, become neutralizing in vivo
      when expressed as Fabs, despite the fact that they are not neutralizing in the
      scFv format. A scFv fragment previously obtained from a neutralizing mouse
      antibody (BCF2) was used to produce three derived scFvs by directed evolution.
      Only one of them was neutralizing, however when expressed as Fab, all of them
      became neutralizing fragments in vivo. The initial scFvBCF2 (earlier used for
      directed evolution) was not neutralizing in the scFv format. After expressing it
      as Fab did not become a neutralizing fragment, but did reduce the intoxication
      symptoms of experimental mice. The stability of the four Fabs derived from their
      respective scFvs was improved when tested in the presence of guanidinium
      chloride. The in vitro stability of the Fab format has been shown earlier, but
      the physiological consequences of this stability are shown in this communication.
      The present results indicate that improved functional stability conferred by the
      Fab format can replace additional maturation steps, when the affinity and
      stability are close to the minimum necessary to be neutralizing.

PMID- 16814389
TI  - Iron(III) complexes of certain meridionally coordinating tridentate ligands as
      models for non-heme iron enzymes: the role of carboxylate coordination.
AB  - The iron(III) complexes [Fe(pda)Cl(H(2)O)(2)] (1), [Fe(tpy)Cl(3)] (2), and
      [Fe(bbp)Cl(3)] (3), where H(2)pda is pyridine-2,6-dicarboxylic acid, tpy is
      2,2':6,2''-terpyridine and bbp is 2,6-bis(benzimidazolyl)pyridine, have been
      isolated and studied as functional models for the intradiol-cleaving catechol
      dioxygenase enzymes. Mixed ligand complexes of H(2)pda with the bidentate ligands
      2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) have been also prepared and
      studied. All the complexes have been characterized using absorption spectral and
      electrochemical methods. The spectral changes in the catecholate adducts of the
      complexes generated in situ have been investigated. Upon interacting the
      complexes with catecholate anions a low energy catecholate to iron(III) charge
      transfer band appears, which is similar to that observed for enzyme-substrate
      complexes. All the complexes catalyze the oxidative intradiol cleavage of 3,5-di
      tert-butylcatechol (H(2)dbc) in the presence of dioxygen. Interestingly, on
      replacing the pyridyl groups in 2 and the bulky benzimidazole groups in 3 by the
      carboxylate groups, the yields of the intradiol cleavage products of
      dioxygenation increases, 1 (50%)>2 (20%)>3 (10%). The higher intradiol yield for
      1 has been ascribed to the meridional coordination of two carboxylate groups of
      pda(2-). In contrast to the trend in the intradiol cleavage yields, a tremendous
      decrease in the rate (200 times) is observed on replacing the two pyridyl
      moieties in 2 by two carboxylates as in 1 and a significant decrease in rate is
      observed on replacing the pyridyl moieties in 2 by strongly sigma-donating
      benzimidazole moieties as in 3. This is in conformity with the decrease in Lewis
      acidities of the iron(III) centers.

PMID- 16814390
TI  - Screening of alpha-1-antitrypsin gene by denaturing gradient gel electrophoresis
      (DGGE).
AB  - Alpha-1-antitrypsin (AAT) is a serine protease inhibitor whose deficiency could
      cause emphysema and liver disease and, as recently described, could be a risk
      factor for lung cancer development. Alpha-1-antitrypsin inhibits a variety of
      proteases but its primary target is neutrophil elastase, an extracellular
      endopeptidase capable of degrading most protein components of the extracellular
      matrix. Inhibition of neutrophil elastase by AAT has an important role in
      maintaining the integrity of connective tissue. The gene encoding for AAT spans
      over 12.2 kb, consists of seven exons and is highly polymorphic. Therefore
      several methods for mutation screening of alpha-1-antitrypsin gene have been
      developed. Method described here is based on denaturing gradient gel
      electrophoresis (DGGE). This method is highly efficient and reliable and allows
      rapid analysis of entire coding region of alpha-1-antitrypsin gene, including
      splice junction sites. Previously described DGGE based analysis of AAT gene
      included overnight electrophoresis of individually amplified fragments. The
      optimization of the method described in this paper is directed towards the
      shortening of the duration of electrophoresis and amplification of fragments in
      multiplex reaction in order to make the analysis less time-consuming and
      therefore more efficient.

PMID- 16814391
TI  - Isolation, cultivation, and differentiation of neural stem cells from adult fish
      brain.
AB  - In contrast to mammals, teleost fish are distinct in their ability to
      continuously produce a tremendous number of new neurons in many regions of the
      adult brain. In the present study, we have isolated intrinsic stem cells from the
      telencephalon, corpus cerebelli, and valvula cerebelli of the teleost Apteronotus
      leptorhynchus and examined their properties in vitro. After 3-4 days in culture,
      neurospheres developed that grew through cell proliferation and reached diameters
      of up to 140 microm within 3 weeks. An increase in the number of developing
      neurospheres could be promoted by addition of epidermal growth factor or basic
      fibroblast growth factor, but no additive effect was observed after combined
      treatment. The number of neurospheres could furthermore be enhanced by seeding
      brain cells at densities of approximately 1 x 10(6). Differentiation conditions
      were optimal by exposing neurospheres to 10% fetal bovine serum and laminin as
      coating substrate. Neurosphere cells gave rise to both neurons, immunopositive
      for Hu-C/D or MAP2 (2a + 2b), and glial cells, immunopositive for glial
      fibrillary acidic protein or vimentin. Since, in addition to their multipotency,
      the cells isolated from the adult teleostean brain exhibited the ability for self
      renewal, we hypothesize that they are true stem cells.

PMID- 16814392
TI  - There is no relation between the fascicular and the endoneural blood vessel areas
      on the cervical vagus nerve of normotensive rats.
AB  - The aim of this study was to determine the existence of a relation between the
      fascicular area and total vessel area on the cervical vagus nerve of Wistar-Kyoto
      female rats. Animals aged 30, 180 or 360 days had their right vagus nerves
      prepared for epoxy resin embedding and light microscopy study. Semithin serial
      sections were studied every 100 microm of the longitudinal extension of the
      nerve. The fascicular area and the total endoneural vessel area were obtained for
      each nerve segment (proximal, middle and distal) and compared between segments
      and ages. The relation between fascicular area and endoneural vessel area was
      accessed by linear regression analysis and correlation coefficient calculations.
      No significant relationship between the two variables was detected in all nerves
      studied. This suggests that the entrance of blood vessels to the endoneural space
      is not accompanied by an increase in the fascicular area and this may have
      implications on the fiber density calculations since, in the presence of large
      vessels, this density can be underestimated if the vessel area is not discounted.
      The endoneural vessel area increased from proximal to distal in all groups but
      got smaller with ageing, suggesting that older animals may be more susceptible to
      nerve ischemia.

PMID- 16814393
TI  - Wiener filter deconvolution of overlapping evoked potentials.
AB  - Evoked potentials (EPs) typically contain components that last up to several
      seconds. In order to save time and study adaptation effects, stimuli are often
      presented at high stimulation rates. Unfortunately, such protocols often suffer
      from a response overlap problem. Techniques based on Continuous Loop Averaging
      Deconvolution (CLAD) have been developed to formulate circular convolution to
      restore the source EP. These techniques, however, are sensitive to the additive
      noise and do not perform well when stimulus sequences with poor noise attenuation
      properties are chosen. This study offers a solution to this problem by applying
      Wiener theory to obtain an optimal filter that adapts the ratio of noise-to
      signal by estimating the power spectra of both noise and signal using non
      parametric or parametric methods. Experiments are conducted on simulation data
      and Auditory Evoked potentials (AEPs) acquired from human subjects to demonstrate
      the validity of the proposed theory. The results show that the Wiener
      deconvolution method improves the quality of the responses acquired with
      sequences with poor noise attenuation in the presence of high noise levels
      compared to the straight CLAD method. The results are comparable to responses
      obtained by conventional and Maximum Length Sequence (MLS) methods.

PMID- 16814394
TI  - pH dependent high transfection efficiency of mouse neuroblastomas using
      TransFectin.
AB  - Mouse neuroblastoma cell lines are often used in lieu of mouse primary neurons in
      ex vivo experiments, as they provide an easier platform for transfection,
      compared to the latter. A well-known inherent problem with this strategy is the
      relatively low transfection efficiency (15-30%) of mouse neuroblastoma cell lines
      such as neuro-2A and N1E-115. We were able to improve the transfection efficiency
      of these cell lines by using the cationic lipid reagent, TransFectin (Bio-Rad,
      Hercules, CA, USA) to optimise the transfection conditions. Our results, based on
      fluorescence intensity determinations and Western blotting for enhanced green
      fluorescence protein (EGFP) over-expression in neuro-2A, demonstrated that pH is
      a crucial factor in determining the transfection efficiency. Under pH-optimised
      transfection conditions, flow cytometric analysis revealed high EGFP transfection
      efficiencies of 76.4 +/- 0.5 and 60.9 +/- 0.6% for neuro-2A and N1E-115,
      respectively. Notably, the optimised TransFectin-based transfection system did
      not result in any detectable cytotoxicity to the mouse neuroblastomas. The
      resultant optimised system is economical, easy to use and does not require any
      specialised equipment.

PMID- 16814395
TI  - Psychotic symptoms in pediatric bipolar disorder and family history of
      psychiatric illness.
AB  - BACKGROUND: Few studies have examined the specificity and non-specificity in
      patterns of familial loading for presentation of psychotic symptoms in pediatric
      bipolar disorder (BP). METHODS: Diagnostic assessment of 263 pediatric BP
      probands included lifetime history of psychotic symptoms as well as longitudinal
      follow-up; family history of psychiatric illness was determined for 1st degree
      relatives. RESULTS: Pediatric BP probands with lifetime history of psychosis had
      a higher percentage of positive family history of anxiety disorders and suicide
      attempts as compared to probands with no history of psychosis. DISCUSSION:
      Familial loading for a spectrum of internalizing disorders is associated with
      presentation of psychotic symptoms in pediatric BP.

PMID- 16814396
TI  - Anger- and aggression-related traits are associated with polymorphisms in the 5
      HT-2A gene.
AB  - BACKGROUND: This study investigates the association of four single nucleotide
      polymorphisms (SNPs) in the serotonin 2A (5-HT-2A) receptor gene with anger-,
      aggression- and suicide-related behavior in a total of 566 subjects (203 German
      suicide attempters and 363 German community-based healthy volunteers). METHODS:
      Anger- and aggression-related traits were assessed by using the State Trait Anger
      Expression Inventory (STAXI) and the Questionnaire for Measuring Factors of
      Aggression (FAF). RESULTS: Three (rs643627-rs594242-rs6311: A-C-T), two (rs594242
      rs6311: C-T) and a single functional (rs6311: T) marker were protective against
      suicidal behavior. The complementary makers (rs594242-rs6311: G-C and rs6311: C)
      were associated with increased risk for non-violent (p=0.01; p=0.009
      respectively) and impulsive suicidal behavior (p=0.03; p=0.01 respectively).
      Furthermore, CC-homozygotes for the functional SNP rs6311 reported more anger-
      (p=0.004) and aggression-related behavior (p=0.011). CONCLUSION: We conclude that
      variations in the 5-HT-2A gene may modify the phenotype of suicide-, anger-, and
      aggression-related behavior. Further studies should especially focus on
      intermediate personality traits in this context.

PMID- 16814397
TI  - Phenytoin as an augmentation for SSRI failures: a small controlled study.
AB  - BACKGROUND: Lithium augmentation of antidepressant effects in patients unimproved
      on antidepressants is well documented. We hypothesized that phenytoin, reported
      to have antimanic, antidepressant and prophylactic effects on affective disorder,
      might also augment in SSRI failures. METHODS: Twenty five patients were recruited
      and twenty had data sufficient for analysis between phenytoin and placebo in
      depression ratings. RESULTS: No effect was found. LIMITATIONS: This study was a
      small study. CONCLUSIONS: Lithium's ability to augment in antidepressant failures
      may not be shared with the anticonvulsant mood stabilizers.

PMID- 16814398
TI  - Life events and clinical subtypes of major depression: a cross-sectional study.
AB  - The present study aimed to investigate the relationship between stressful life
      events and depression. Ninety major depressive patients, aged 36.57 +/- 12.02
      years, and 121 matched controls, aged 27.11 +/- 10.59 years, took part in the
      study. The life change units (LCU) according to Rahe et al. were used for the
      quantification of life events. The results suggested that males reported
      significantly more life events than females. Atypical males differed from all
      other gender-by-type groups, while no other differences emerged. LCU correlated
      with melancholic indices but did not correlate with anxiety or functioning. The
      results suggest that subgroups of depressive patients are characterized by the
      presence of stressful life events. Male atypical patients reported the highest
      load of life events. The question that arises is whether this finding is valid or
      whether these patients (who have higher personality psychopathology and
      interpersonal rejection sensitivity) tend to over-report life events.

PMID- 16814399
TI  - Mannan binding lectin and its interaction with immunoglobulins in health and in
      disease.
AB  - In humans there are five classes of immunoglobulins (Igs), IgG, IgM, IgA, IgE and
      IgD, all of which are glycoproteins. The Igs are the major secretory product of
      the adaptive immune system, and they bind to antigens via variable sequences on
      their Fab regions. The binding to antigen results in neutralization or
      agglutination of bound material and also initiates effector functions via the Fc
      regions, such as opsonisation and activation of the classical complement pathway
      through binding of C1q. Mannan binding lectin (MBL), the 'recognition' molecule
      of the lectin pathway of complement activation, is homologous in structure to
      C1q, and binds in a calcium-dependent manner to terminal mannose and GlcNAc
      residues which have been identified on the oligosaccharides N-linked to the Igs.
      MBL binds agalactosylated glycoforms of IgG (IgG-G0), polymeric forms of IgA and
      certain glycoforms of IgM which have a high incidence of GlcNAc-terminating
      glycans. This interaction provides a route of clearance of immune complexes from
      the serum, and a mechanism of complement activation to Ig-coated pathogens. In
      disease, MBL contributes to inflammation in Rheumatoid Arthritis, a condition in
      which serum IgG-G0 concentrations can increase significantly compared to healthy
      individuals. MBL has recently been demonstrated to bind Ig in the B cell receptor
      complex which expresses abnormal variable region glycosylation, in follicular
      lymphoma.

PMID- 16814400
TI  - Expression of mRNA for multiple serotonin (5-HT) receptor types/subtypes by the
      peripheral blood mononuclear cells of rhesus macaques.
AB  - To find out whether rhesus macaque peripheral blood mononuclear cells (PBMCs)
      express mRNA for 5-HT receptors, blood samples from normal healthy rhesus monkeys
      were used to isolate PBMCs by Ficoll-paque density gradient centrifugation. Total
      RNA was extracted from MT-2 cells, Hut-78 cells, naive or phytohemagglutinin
      (PHA) stimulated human and monkey PBMCs. One tube RT-PCR was performed using
      primers specific for human 5-HT1A, 5-HT1B, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3,
      5-HT4, 5-HT6, and 5-HT7 receptors. Amplicons of expected sizes were obtained from
      human cell lines as well as both human and monkey PBMCs. Both PHA stimulated
      human and monkey PBMCs express mRNAs for 5-HT1A, 5-HT1B, 5-HT1E, 5-HT2A, 5-HT3, 5
      HT4, 5-HT6 receptor types/subtypes. However, mRNAs for 5-HT1B, 5-HT1E and 5-HT2A
      cannot be confidently detected in some of the PBMC samples without PHA
      stimulation. 5-HT2B and 5-HT7 receptor mRNA was not detected in most of the
      samples and 5-HT2C receptor mNRA was not detected at all. FACS analysis revealed
      that CD3+ lymphocyte increased more than 20% among lymphocytes in the PHA
      stimulated PBMCs. These data indicate that similar to human PBMC, rhesus macaque
      PBMC may express multiple types of 5-HT receptors and the expression profile
      could change after PHA stimulation due to either the changes in cell composition
      or changes in gene transcription level. This provided a basis for further studies
      on the neuroimmunomodulatory interactions of 5-HT in rhesus macaques.

PMID- 16814401
TI  - Comparison of self-esteem level of adolescents with cochlear implant and normal
      hearing.
AB  - OBJECTIVE: The purpose of this study is to compare the levels of self-esteem of
      adolescents with cochlear implants (before and after cochlear implantation) and
      the ones who have normal hearing. METHODS: For this purpose, Rosenberg self
      esteem scale is applied upon the study group which consists of 30 adolescents
      with cochlear implant between the ages of 12-19 and upon the control group which
      consists of 60 adolescents having the similar characteristics. The scale is used
      to evaluate the level of self-esteem of adolescents with cochlear implant and
      with normal hearing. RESULTS: At the end of the application, the scores of these
      two groups which they got according to their answers were compared statistically.
      When the results were examined, there seemed to be no significant difference
      statistically between the self-esteem values of the cochlear implant group and
      the control group. Apart from this, there seemed to be significant difference
      statistically between the self-esteem values of the before cochlear implantation
      and control group. In this study, we examined changes in the level of self-esteem
      according to different variables. As a result, it was found out that in both
      groups levels of self-esteem was higher for adolescents who had had preschool
      education, had brothers/sisters, high level of income, whose mother was working
      and whose father and mother had higher levels of education. On the other hand,
      the birth sequence and the child's father's profession did not seem to have any
      effect on the child's level of self-esteem. CONCLUSIONS: As a result of these
      findings, it was thought that cochlear implantation had a positive effect on life
      quality and it was suggested that the adolescents and their families should get
      assistance from experts about the characteristics and principles of approaching
      the child in this period. The adolescent should be directed towards social
      activities and courses, their positive sides should be supported and further
      studies should be carried out with different case groups on this matter.

PMID- 16814402
TI  - Pre-surgical child behavior ratings and pain management after two different
      techniques of tonsil surgery.
AB  - OBJECTIVE: The purpose of this investigation was to compare child behavior before
      surgery with experience of pain and anxiety in relation to two techniques of
      tonsil surgery, to relate previous experiences of surgery/tonsillitis with
      anxiety and pain, and to compare the children's, parent's and nurse's rating of
      pain. METHOD: Ninety-two children (5-15 years) with sleep-disordered breathing
      (SDB) and with or without recurrent tonsillitis were randomized to partial tonsil
      resection/tonsillotomy (TT) or full tonsillectomy (TE). MEASURES: Parents: Child
      Behavior Checklist (CBCL). Children: State-Trait-Anxiety Inventory for Children
      (STAIC) and seven-point Faces Pain Scale (FPS). Parents/staff: seven-point Verbal
      Pain Rating Scale (VPRS). Pain relievers were opoids, paracetamol and
      diclophenac. RESULTS: These children with SDB scored significantly higher on CBCL
      than did normative groups, but no connection was observed between CBCL rating and
      experience of pain. There was no relation between pre-operative anxiety and pain.
      The post-operative anxiety level (STAIC) correlated with pain. The TE-group
      scored higher on STAIC after surgery. Previous experience of surgery or
      tonsillitis did not influence post-operative pain. The TE-group rated higher
      experience of pain despite more medication. The nurses scored pain lower than the
      parents/children and under-medicated. CONCLUSION: SDB may influence children's
      behavior, but with no relation to post-operative pain. The surgical method
      predicts pain better than does the child's behavior rating. The nurses
      underestimated the pain experienced by the child.

PMID- 16814403
TI  - A high prevalence of new onset otitis media during parent diagnosed common colds.
AB  - INTRODUCTION: Past studies suggest that the majority of new otitis media (OM)
      diagnoses is a complication of a colds/flu. A prospective format was used to
      determine the coincidence of otitis media and parent diagnosed cold/flu episodes
      in young children followed over a typical cold/flu season. METHODS: Eighteen
      families with children aged 1-8 years were followed from October 1 to April 30
      using parent-completed daily diaries focused on cold/flu signs and weekly
      examinations using pneumatic otoscopy for diagnosis of the presence/absence of
      otitis media. RESULTS: Overall, 108 cold episodes were documented in 36 enrolled
      children with 20 colds (19%) occurring during a pre-existing OM episode and 40
      colds (37%) complicated by a new OM episode. Conversely, there were 82 new OM
      episodes, 40 (49%) were associated with a cold in the individual child and 18
      (22%) with a concurrent cold in a family member. The median duration of the OM
      episodes was approximately 2 weeks but this was longer for OM episodes where
      earache was reported. CONCLUSION: The results confirm past observation relating
      new OM episodes to a concurrent cold/flu but show these episodes to usually be of
      short duration. Two sources of potential bias were identified for point
      prevalence study formats: the presence of a pre-existing OM for a new onset
      cold/flu and the possibility of subclinical colds in patients with new OM
      episodes. These biases reinforce the need for longitudinal study formats to
      address this important relationship.

PMID- 16814404
TI  - Medial migration of tympanostomy tubes: an overlooked complication.
AB  - BACKGROUND: Frequently encountered complications associated with tympanostomy
      tube placement have been well documented and are globally recognized. The medial
      migration of tympanostomy tubes into the middle ear space is a rare complication
      for which pathogenesis, natural history, and management have not been clearly
      delineated. OBJECTIVE: To describe our experience with the medial migration of
      tympanostomy tubes into the middle ear space. To propose a simple classification
      system and define management recommendations. METHODS: A retrospective chart
      review of all patients with medial tube migration seen in a Pediatric
      Otolaryngology practice at a tertiary care university hospital between 1995 and
      2005. RESULTS: Six pediatric patients (ages 3-19) were found to have seven
      tympanostomy tubes within the middle ear space at various intervals following
      tube placement. One patient had a migrated tympanostomy tube deep to a large
      myringotomy incision. Five patients (six ears) had migrated tubes medial to
      intact, healed tympanic membranes. Fifty percent of the patients had symptoms
      attributable to the migrated tube. All six patients underwent middle ear
      exploration with successful removal of the migrated tube. CONCLUSIONS: This
      process can be defined as primary, when the tympanostomy tube migrates due to a
      technical error, or secondary, when the tube is initially seen in the correct
      position but is later found medial to a healed, intact tympanic membrane. Medial
      migration is apparently independent of tube type and can occur at various
      intervals after placement. The process of secondary migration is most likely
      multifactorial but may in part be the result of persistent negative middle ear
      pressure. Migrated tubes should be removed surgically unless contraindicated.

PMID- 16814405
TI  - Effects of copper on CYP1A activity and epithelial barrier properties in the
      rainbow trout gill.
AB  - The effects of copper on beta-naphthoflavone (betaNF)-induced ethoxyresorufin O
      deethylase (EROD) activity were studied in rainbow trout (Oncorhynchus mykiss)
      gill filaments (after in vivo exposure) and in gill cells cultured as both
      primary cultures and as polarised epithelia, i.e. with water in the apical
      compartment and culture medium in the basolateral compartment. In the in vivo
      study betaNF and copper were added to the water, in primary cultures both
      chemicals were added to the culture medium and in cultured epithelia copper was
      added to the apical water whilst betaNF was added to the basolateral culture
      medium. In primary cultures this investigation was repeated with and without
      foetal bovine serum (FBS) supplementation of the culture media. Gill barrier
      properties, specifically polyethylene glycol (PEG-4000) permeability (i.e.
      paracellular permeability), sodium efflux and transepithelial electrical
      resistance (TER) were also investigated in cultured gill cell epithelia after
      apical treatment with copper. Two micromolar copper had no effect on EROD
      activity in gill filaments in vivo irrespective of whether EROD was induced by
      0.01, 0.1 or 1.0 microM betaNF. Similarly, 0.5-100 microM copper had no effect on
      EROD induction in cultured epithelia. In primary cultures copper did reduce EROD
      induction but the effective concentration was dependent on whether the cells were
      supplemented with FBS, i.e. EROD activity was reduced by all copper
      concentrations of 5 and above if FBS was included, but only by 1000 microM if FBS
      was omitted. In cultured epithelia PEG-4000 permeability increased, whilst sodium
      efflux and TER were unaffected following treatment with 75 microM copper. Based
      on these results we conclude that the branchial monooxygenase system is a less
      sensitive target for copper than the barrier properties of the gill. Indeed,
      these data suggest the apical membrane of the gill epithelial cells minimises the
      uptake of waterborne copper and therefore protects the intracellular environment,
      including the CYP1A system. This could enable the freshwater fish gill to retain
      their potential of first-pass metabolism of waterborne organic compounds whilst
      simultaneously being exposed to waterborne copper.

PMID- 16814406
TI  - Effects of cholecystokinin-8 induced gastric dysmotility on bile regurgitation
      during stress and molecular mechanisms.
AB  - OBJECTIVE: To illustrate the existence of bile regurgitation under stress
      condition, and explore the possible effects and related mechanism of changes of
      plasma cholecystokinin octapeptide (CCK-8) and intragastric pH on stress-induced
      bile regurgitation in rats. METHODS: (1) Changes in plasma CCK-8 and gastric bile
      concentration were respectively measured by using radioimmunoassay (RIA) method
      while simultaneously calculating gastric ulcer index (UI) 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 group, plasma CCK-8 and gastric bile concentration
      significantly increased during stress (p<0.01) and both simultaneously reached
      the peak at the time point of 2 h after stress; UI and intragastric pH apparently
      increased (p<0.01); (2) Significant changes to CCK-8S were found in the mean
      contractile amplitude and frequency of circular muscle (CM) and longitudinal
      muscle (LM) of gastric antrum and pylorus; (3) CCK-8S-evoked significant increase
      in [Ca(2+)]i (p<0.01) could be suppressed by CCK-A receptor (CCK-AR) antagonist;
      whereas a small but significant increase was still elicited by CCK-8S under
      condition of the removal of extracellular calcium or by given nifidipine; (4) CCK
      8S-intensified calcium current (I(CaL)) apparently inhibited by respective
      administration of nifidipine, Ca(2+)-ATPase inhibitors or calcium dependent
      chloride channel (I(Cl-Ca)) blocker (p<0.01). CONCLUSION: 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 (VDCC) through the activation of calcium dependent chloride channels.

PMID- 16814407
TI  - Interaction of atrial natriuretic peptide, urodilatin, guanylin and uroguanylin
      in the isolated perfused rat kidney.
AB  - Escherichia coli heat-stable enterotoxin (STa), guanylin and uroguanylin are
      novel natriuretic and kaliuretic peptides that bind to and activate membrane
      guanylate cyclase (GC) receptors such as GC-C and OK-GC that are expressed in the
      kidney and intestine. Atrial natriuretic peptide (ANP) and its renal form
      (urodilatin, UROD) elicit natriuretic effects by activation of a different
      membrane guanylate cyclase, GC-A. Experiments were done in perfused rat kidneys
      to search for possible synergistic interactions between ANP, UROD, guanylin and
      uroguanylin on renal function. Pretreatment with ANP (0.03 nM) enhanced guanylin
      (0.19 microM) natriuretic activity (%ENa(+); from 18.5+/-4.25 to 31.5+/-1.69,
      P<0.05, 120 min) and its kaliuretic activity (%EK(+); from 24.5+/-4.43 to 50.6+/
      3.84, P<0.05, 120 min). Furthermore, ANP increased the natriuretic (29.05+/-3.00
      to 37.8+/-2.95, P<0.05, 120 min) and kaliuretic (from 33.2+/-3.52 to 42.83+/
      2.45, P<0.05, 120 min) responses of perfused kidneys treated with low-dose (0.06
      microM) uroguanylin. In contrast, ANP clearly inhibited the uroguanylin-induced
      (0.31 microM) increase in %ENa(+) (from 35.9+/-2.37 to 14.8+/-1.93, P<0.05, 120
      min), and in %EK(+) (from 51.0+/-4.43 to 38.8+/-3.61, P<0.05, 120 min). UROD
      (0.03 nM) also enhanced the guanylin-induced natriuresis (to %ENa(+)=31.0+/-1.93,
      P<0.05, 120 min) and kaliuresis (to %EK(+)=54.2+/-3.61, P<0.05, 120 min), and
      inhibited the %ENa(+) of uroguanylin (0.31 microM) to 17.9+/-1.67 as well as its
      %EK(+) to 24.3+/-3.13 (both at 120 min, P<0.05). The synergism between ANP and
      UROD with either guanylin or uroguanylin at sub-threshold doses and the
      unexpected antagonism between ANP and UROD with uroguanylin at a pharmacological
      dose point to possible interactions between natriuretic peptide receptor (NPR)
      and uroguanylin/guanylin receptor signaling pathways. The interactions herein
      described may play a contributory role in the regulation of kidney function in
      many pathophysiological states, such as in the saliuresis following ingestion of
      salty meals.

PMID- 16814408
TI  - Promoter characterization and transcriptional regulation of Ncb5or, a novel
      reductase necessary for pancreatic beta-cell maintenance.
AB  - Ncb5or is a ubiquitously expressed gene required for beta-cell survival in mice.
      Examination of mouse tissues demonstrated high levels of expression in the
      pancreas, heart and kidney. A transcription start site was identified 149 bp
      upstream from the start codon and transient expression analysis in betaTC3 cells
      indicated the presence of a core promoter located within 348 bp upstream of this
      site. Deletion of Region C (-216/-157) resulted in a significant decrease in
      promoter activity and specific nucleotides located in a region designated C2 were
      demonstrated to be critical for complex binding. Deletion of Region D (-60/-33),
      which contains multiple consensus Sp1 sites, resulted in an additional loss of
      promoter activity. The data presented here identify and characterize the
      previously unknown promoter of Ncb5or, a reductase critical for beta-cell
      survival.

PMID- 16814409
TI  - Reduction of invasion in human fibrosarcoma cells by ribosomal protein S3 in
      conjunction with Nm23-H1 and ERK.
AB  - RpS3 is a component of the 40S ribosomal subunit of eukaryotes and also plays a
      role as a base damage endonuclease. Nm23-H1 encodes nucleoside diphosphate kinase
      A and acts as a suppressor of metastasis in certain human tumors. RpS3 interacted
      with nm23-H1, and the two proteins were colocalized in the cell periphery and
      cytoplasm. The 190th leucine of rpS3, and the 118th histidine and the 120th
      serine of nm23-H1 play key roles in the interaction of two proteins,
      respectively. The expression of rpS3 reduced the secretion of MMP-9 and the
      invasive potential in HT1080 cells. Additionally, the phosphorylated ERK was
      reduced by the expression of rpS3. In MCF7 cells, where the ERK pathway is
      inactivated and MMPs are not secreted and the ERK pathway can be activated by
      PMA, the PMA-induced ERK phosphorylation was reduced by the expression of rpS3.
      However, the L190A mutant of rpS3, which did not interact with nm23-H1, did not
      inhibit the invasive potential, the secretion of MMP-9, and the activation of the
      ERK pathway in HT1080 cells and PMA-activated MCF7 cells. These results suggest
      that rpS3 inhibits invasion via blocking the ERK pathway and MMP-9 secretion; the
      results also suggest that the interaction of rpS3 and nm23-H1 appears to be
      critical in this inhibition.

PMID- 16814410
TI  - Combined utility of brain natriuretic peptide and cardiac troponin T may improve
      rapid triage and risk stratification in normotensive patients with pulmonary
      embolism.
AB  - BACKGROUND: Evaluation of the combined utility of brain natriuretic peptide (BNP)
      and cardiac troponin T (cTnT) for risk stratification in normotensive patients
      with acute pulmonary embolism. The changing patterns of BNP and cTnT levels
      during the initial management of pulmonary embolism and their correlation with
      clinical outcome were the focus of this study. METHODS: BNP and cTnT levels were
      measured in 28 consecutive normotensive on admission patients (age 53+/-18 years)
      with acute pulmonary embolism. Twenty-seven healthy age-matched volunteers served
      as controls (age 42+/-12 years). Blood samples from all patients were obtained
      during the first hour of presentation. Follow-up blood samples were acquired
      after 90 days. RESULTS: Six patients (2%) had increased BNP (59+/-30 pmol/L) and
      cTnT (0.044+/-0.025 ng/mL) and RV dysfunction as diagnosed by echocardiography.
      Two of these patients died during follow-up as a consequence of RV failure due to
      pulmonary embolism. Eight patients (29%) had increased BNP (40.6+/-32.6 pmol/L)
      and normal cTnT at presentation. In four of these patients BNP levels remained
      increased after treatment (46.9+/-21.0 pmol/L). During follow-up these patients
      were diagnosed with chronic PE and RV pressure overload (RVSP>40 mm Hg). Fourteen
      patients (50%) with confirmed pulmonary embolism had normal BNP and cTnT levels
      at presentation, which remained normal during follow-up. These 14 patients were
      in good clinical condition during follow-up. CONCLUSIONS: Combined use of BNP and
      cTnT may be useful in risk stratification of normotensive patients with acute
      pulmonary embolism. Patients with increased BNP and cTnT are at risk for adverse
      outcome. Future studies in larger numbers of patients are needed to confirm the
      usefulness of biomarkers in the clinical management of individual patients.

PMID- 16814411
TI  - Impact of specialist care in patients with newly diagnosed heart failure: a
      randomised controlled study.
AB  - AIM: To assess the feasibility and impact of specialist care in patients with
      newly diagnosed heart failure in primary and secondary care. METHODS: Patients
      with suspected heart failure referred for open access echocardiography to a
      hospital-based echocardiography service were assessed from June 2002 through to
      June 2003. Patients with confirmed left ventricular systolic dysfunction (LVSD)
      were randomised to specialist care (cardiology registrar and heart failure
      nurses) or referred back to their general practitioner (GP). Randomisation was
      stratified for age and sex and both groups were comparable. All patients were
      followed up for a minimum of 3 months post randomisation with a mean follow-up
      time of 10+/-3 months. Specialist care was provided both in the community and in
      hospital. The primary endpoint was prescription of optimum heart failure
      medication and secondary endpoint was a composite endpoint of all cause mortality
      and/or hospital admission. RESULTS: 386 patients were screened; mean age -72+/-10
      years. 113 (29%) had confirmed LVSD on echocardiography and were randomised to
      specialist or primary care. The prescription of ACE-inhibitors (85% vs. 64%) and
      beta blockers (50% vs. 2%) was higher in patients randomised to specialist care.
      No significant differences were noted in mortality or hospitalisation.
      CONCLUSION: Specialist heart failure care results in higher rates of optimal
      prescribing, in primary and secondary care.

PMID- 16814412
TI  - Acute administration of 17beta-estradiol reduces endothelin-1 release during
      pacing-induced ischemia.
AB  - OBJECTIVES: To assess whether acute administration of 17beta-estradiol reduces
      pacing-induced cardiac release of endothelin-1 in female menopausal patients with
      coronary artery disease. BACKGROUND: Endothelin-1 is a potent vasoactive peptide
      which plays a pathogenetic role in myocardial ischemia and adverse clinical
      events in patients with coronary artery disease. Estrogens decrease plasma levels
      of endothelin-1 and improve stress-induced myocardial ischemia in menopausal
      women with coronary artery disease. METHODS: Twenty-two postmenopausal women with
      angiographically proven coronary artery entered a randomized, double blinded,
      placebo-controlled study. Patients were sampled into the coronary sinus and aorta
      for endothelin-1 at baseline and after incremental pacing. After baseline study,
      patients were randomized to receive either sublingual 17beta-estradiol (1 mg) or
      placebo and underwent the sampling protocol 20 min thereafter. RESULTS: 17Beta
      estradiol but not placebo improved the time of onset of myocardial ischemia
      during pacing. The coronary sinus plasma levels of endothelin-1 were
      significantly reduced by estradiol administration but not by placebo, at each
      step of pacing protocol. The maximum reduction of endothelin-1 was noted at peak
      pacing (-0.18 ng/l; -0.09, -0.3; 95% CI). No changes in endothelin-1 were noted
      in patients allocated to placebo (-0.002 ng/l; -0.06, -0.01; 95% CI). Similarly,
      aorto-coronary sinus difference of endothelin-1 was significantly influenced by
      17beta-estradiol administration but not by placebo. CONCLUSION: Acute
      administration of 17beta-estradiol reduces pacing-induced cardiac release of
      endothelin-1 in postmenopausal women with coronary artery disease. This result
      may be related to the anti-ischemic or to a primary direct effect of the hormone
      upon myocyte release of the peptide, and may contribute to its anti-ischemic
      effect. CONDENSED ABSTRACT: To assess effect of acute 17beta-estradiol
      administration on pacing-induced cardiac release of endothelin-1, we studied 22
      female menopausal patients with coronary artery diseases. In a randomized, double
      blinded, placebo-controlled study, patients were randomized to receive either
      sublingual 17beta-estradiol (1 mg) or placebo. Aortic and coronary sinus plasma
      endothelin-1 levels were evaluated at baseline, during incremental atrial pacing,
      and at peak pacing before and after the sublingual administration of either
      17beta-estradiol or placebo. The time to the onset of myocardial ischemia during
      pacing was significantly increased by 17beta-estradiol vs. placebo. Moreover,
      coronary sinus endothelin-1 levels at peak pacing and aortic-coronary sinus
      changes were significantly improved by the administration of 17beta-estradiol but
      not by placebo. Acute administration of 17beta-estradiol reduces pacing-induced
      cardiac release of endothelin-1 in postmenopausal women with coronary artery
      disease.

PMID- 16814413
TI  - The association of human connexin 40 genetic polymorphisms with atrial
      fibrillation.
AB  - BACKGROUND: There is evidence showing that genetic factors contribute to the
      pathogenesis of atrial fibrillation (Af). We investigated the association between
      Af and polymorphisms of the connexin 40 (Cx40) gene, which is important in the
      electrical coupling between atrial myocytes. METHODS: We performed an association
      study between two Cx40 single nucleotide polymorphisms (SNPs) (Cx40 -44 and +71
      allele) and Af. We enrolled 173 patients with Af, and the control group consisted
      of 232 patients without Af. The luciferase assay was performed to evaluate the
      promoter activities of different Cx40 haplotypes in cultured atrial myocytes.
      RESULTS: We found that the two SNPs were both significantly associated with Af.
      In pairwise linkage disequilibrium analysis, the two SNPs were completely linked
      (Cx40 -44G always associated with Cx40 +71A; Cx40 -44A associated with Cx40 +71G,
      P<0.001). In haplotype analysis, we demonstrated that the frequency of Cx40 (
      44A,+71G) was significantly higher in the Af group than that in the control group
      (P<0.006, odds ratio=1.514, 95% confidence interval 1.13-2.04). We also performed
      genotype analysis using several genetic models, finding that the recessive model
      showed the lowest P value (P<0.004) and the largest odds ratio (2.53, 95%
      confidence interval 1.23-5.19). In promoter activity studies using luciferase as
      the reporter, Cx40 (-44A,+71G) had significantly lower promoter activity than
      that of the Cx40 (-44G,+71A) in atrial myocytes. CONCLUSIONS: The two SNPs in the
      promoter region of the Cx40 gene were significantly associated with Af. The Cx40
      (-44A +71G) haplotype was associated with a higher risk for Af. This haplotype
      also had significantly lower promoter activity in atrial myocytes.

PMID- 16814414
TI  - Intravenous N-acetylcysteine for preventing contrast-induced nephropathy: a
      randomised trial.
AB  - BACKGROUND: Studies evaluating the role of N-acetylcysteine in patients
      undergoing coronary angiography have yielded inconsistent data. Less is known
      about patients with normal renal function at baseline. METHODS: Prospective,
      double-blind, placebo-controlled trial to determine the benefits of intravenous N
      acetylcysteine as an adjunct to hydration in this kind of population. Patients
      were randomly assigned to receive either N-acetylcysteine (600 mg twice daily) or
      placebo, in addition to 0.45% intravenous saline. The primary end point was
      development of contrast-induced nephropathy, defined as an acute increase in the
      serum creatinine concentration > or = 0.5 mg/dl and/or > 25% increase above
      baseline level at 48 h after contrast dosing. RESULTS: A total of 216 patients
      were studied: N-acetylcysteine = 107 and placebo = 109. Treatment groups were
      similar with respect to baseline clinical characteristics. Overall incidence of
      contrast-induced nephropathy was 10.2%, 10.3% in the N-acetylcysteine group and
      10.1% in the placebo group. Furthermore, no significant differences were observed
      when considering the non-diabetic population, although there was a trend towards
      a protective effect of N-acetylcysteine in the subgroup of 47 patients with both
      hypertension and diabetes. There were no significant changes in serum urea
      nitrogen concentrations. The incidence of in-hospital adverse clinical events was
      low: no patient with contrast-induced nephropathy required dialysis, the median
      Coronary Unit stay was 4.5 vs. 4 days, and the mortality rate was 2.8% vs. 4.6%
      in the N-acetylcysteine and placebo groups, respectively (p=NS). CONCLUSIONS: The
      prophylactic administration of intravenous N-acetylcysteine provides no
      additional benefit to saline hydration in high-risk coronary patients with normal
      renal function.

PMID- 16814415
TI  - CALORIE is a better acronym than CALERIE.

PMID- 16814416
TI  - Long-term outcome of patients with atrioventricular node reentrant tachycardia.
AB  - BACKGROUND: Little information is available on the natural history of patients
      with AVNRT. The purpose of this study was to compare the outcome of patients with
      Atrioventricular node reentrant tachycardia (AVNRT) who underwent ablation with
      those on antiarrhythmic therapy and those not receiving drugs. METHODS: 93
      consecutive patients (mean age=33.5+/-18.1 years) with AVNRT referred to our
      institution from 1988 to 1993 were prospectively followed-up for a mean of 13.2+/
      2.0 years (range=11.4-16.1 years). RESULTS: 18 patients underwent ablation (group
      1), 24 received antiarrhythmic therapy (group 2), 38 received no drugs or
      remained on drug therapy for only few months (group 3), 3 died and 10 were lost
      to follow-up. The frequency of symptoms at the baseline was higher in group 1
      than in groups 2 and 3 (7.8+/-3.7, 3.5+/-2.3, 2.3+/-1.9 episodes/month,
      respectively; p<0.02 in group 1 vs. group 3). At the end of the follow-up 18/18
      (100%) of group 1, 14/23 (61%) of group 2 and 17/38 of group 3 (44.7%) reported
      being asymptomatic for the previous 3 years. Group 3 patients who became
      asymptomatic had a shorter duration of symptoms before enrolment (3.7+/-1.5 vs.
      7.1+/-3.6 years, p<0.05) and a shorter mean length of the tachycardia episodes
      (3.8+/-2.4 vs. 42.6+/-17.8 min, p<0.02) than patients from the same group who
      remained symptomatic. CONCLUSIONS: The main result of this study is that during a
      long-term follow-up a considerable number of untreated patients with AVNRT become
      asymptomatic. This finding should be considered for choosing treatment modality
      and for calculating healthcare costs of ablation vs. medical therapy.

PMID- 16814417
TI  - Prediction of infarction-related artery occlusion and multivessel disease in
      postinfarction angina.
AB  - CONDENSED ABSTRACT: To investigate the predictive value of clinical data for
      infarction-related artery (IRA) occlusion and multivessel coronary disease in
      postinfarction angina (PIA), we studied 181 consecutive patients presenting PIA
      following a first uncomplicated ST elevation AMI. Multivariate analysis showed
      ECG changes during PIA and the absence of thrombolytic therapy as independent
      predictors of IRA occlusion. Independent clinical predictors of multivessel
      coronary disease were age, previous history of angina and the number of
      cardiovascular risk factors. We conclude that reversible ECG changes during PIA
      correlated to IRA occlusion but failed to predict a multivessel coronary disease.
      AIM: To identify clinical variables predictive of infarction-related artery (IRA)
      occlusion and multivessel coronary disease in patients with postinfarction angina
      pectoris (PIA) after a first uncomplicated acute myocardial infarction (AMI).
      METHODS: We studied 181 consecutive patients with PIA following a first
      uncomplicated AMI. Clinical variables included cardiovascular risk factors,
      clinical history of angina before the event of inclusion, use of thrombolytic
      therapy in the previous AMI, ST-T changes during PIA, time to onset, number of
      episodes and delay to angiography after PIA. Angiographic variables were IRA TIMI
      flow, number of diseased vessels and ventricular function. RESULTS: The IRA was
      occluded in 67 patients with PIA (37.0%). Reversible ECG changes during PIA were
      detected in 121 patients (67.0%): 79 cases (43.6%) with ST/T elevation and 42
      cases (23.2%) with ST/T depression. Multivariate logistic regression analysis
      showed ECG changes during PIA (OR 3.12 CI 95% 1.48-6.54, p<0.01) and the absence
      of thrombolytic therapy (OR 2.21 95% CI 1.11-4.43, p<0.05) as independent
      predictors of IRA occlusion. We found multivessel coronary disease in 89 patients
      (49.2%) without any correlation to ECG changes during PIA. Independent clinical
      predictors of multivessel coronary disease were age (OR 1.03 95% CI 1.01-1.06,
      p<0.05), previous history of angina (OR 2.37 95% CI 1.06-5.28, p<0.05) and the
      number of cardiovascular risk factors (OR 1.37 95% CI 0.97-1.92, p=0.07).
      CONCLUSIONS: ECG changes during PIA was correlated to IRA occlusion in spite of
      previous thrombolytic therapy but failed to predict a multivessel coronary
      disease in our patients.

PMID- 16814418
TI  - Equine trypanosomosis in the Central River Division of The Gambia: a study of
      veterinary gate-clinic consultation records.
AB  - The objective of this study was to provide epidemiological information of equine
      trypanosomosis in the Central River Division (CRD) of The Gambia. Therefore, 2285
      consultations records of equines, admitted in a gate-clinic at Sololo in CRD,
      were studied retrospectively. The data were recorded in the period between
      September 1995 and July 2002 and comprised consultations of 2113 horses and 172
      donkeys. 'Trypanosome infection' was the most frequently diagnosed condition and
      accounted for 61% of the cases. Horses were more frequently diagnosed with
      trypanosome infections than donkeys (p<0.001), with an occurrence of 63% compared
      to 43% in donkeys. In both horses and donkeys, trypanosome infections were mainly
      due to Trypanosoma congolense (64%) and T. vivax (32%). There was no difference
      observed in the occurrence of trypanosome infections in male or female donkeys
      (p=0.585), but there were more female (67.8%) horses observed with trypanosome
      infections than male horses (60.7%; p=0.003). There was no difference observed in
      the occurrence of trypanosome infections in donkeys older or younger than 1 year
      (p=0.130), but more older horses (63.2% >1 year) were observed with trypanosome
      infections than young horses (54.5% <1 year; p=0.033). The number of donkeys and
      horses with trypanosome infections decreased during the rainy season (June
      September). The majority of equines that were admitted with trypanosome
      infections were severely anaemic. The average packed cell volume (PCV) declined
      with increasing parasitaemia (p=0.006). Seventy-four percent of the farmers'
      predictions of trypanosome infections in their equines were confirmed by
      darkground-microscopy. That proved that farmers had a fairly accurate knowledge
      of the diseases affecting their equines. The treatments executed at the gate
      clinic were generally effective. The few (0.4%) relapses of the T. vivax
      infections that were previously treated with diminazene aceturate in this study
      were not sufficient to prove drug resistance. The study showed that the analysis
      of consultation records at a gate-clinic can provide complementary information to
      conventional epidemiological studies in the same research area.

PMID- 16814419
TI  - In house reverse line hybridization assay for rapid detection of susceptibility
      to rifampicin in isolates of Mycobacterium tuberculosis.
AB  - We developed a Reverse Hybridization Assay (RHA) slightly modified from the
      Rifoligotyping assay and analyzed the presence of mutations in a specific region
      of rpoB gene in 157 isolates (90 rifampin-resistant and 67 rifampin sensitive) of
      Mycobacterium tuberculosis from patients attended in South and Southeast region
      of Brazil. Comparing to standardized drug susceptibility testing results, the
      sensitivity and specificity of the RHA was respectively 93% (95% IC: 86.6%-97.2%)
      and 100% respectively. Additionally, a high agreement (kappa coefficient 95%)
      between the RHA assay and sequencing was obtained. Among the 90 rifampicin
      resistant isolates, RHA identified point mutations in the following codons: 42
      isolates (46.6%) in 531; 29 isolates (32.2%) in 526, 6 isolates (6.7%) in 516, 3
      isolates (3.3%) in 522, 2 isolates (2.2%) in 515, 514, 513 and 1 isolate (1.1%)
      in 511, 524 and 525. Mutations in different codons were simultaneously identified
      in 8 isolates (8.9%). The RHA used in the present study had a high accuracy and
      can be rapidly performed. However, more reproducible hybridization conditions
      should be looked for to increase reliability of mutant probe interpretation.

PMID- 16814420
TI  - The parafascicular nucleus relays spinal inputs to the striatum: an electron
      microscope study in the rat.
AB  - A disynaptic projection from the spinal cord to the striatum was observed in the
      rat light and electron microscopically. An anterograde tracer, wheat germ
      agglutinin conjugated to horseradish peroxidase was injected into the ventral
      gray matter of the upper cervical spinal cord, and a retrograde tracer,
      biotinylated dextran amine was injected into the striatum of a rat. Then the
      parafascicular nucleus was examined. Some anterogradely labeled axon terminals
      originating in the spinal cord were observed to synapse with retrogradely labeled
      dendrites of parafascicular nucleus neurons which sent axons to the striatum. We
      concluded that information from the spinal cord was transmitted to the striatum,
      being relayed by parafascicular nucleus neurons.

PMID- 16814421
TI  - Glial cell-derived neurotrophic factor (GDNF) promotes low-grade Hs683 glioma
      cell migration through JNK, ERK-1/2 and p38 MAPK signaling pathways.
AB  - Invasion of tumor cells is the primary cause of therapeutic failure in the
      treatment of malignant gliomas. In an attempt to investigate the properties of
      the malignant progression of glioma cells, we examined the correlation between
      cell migration and glial cell-derived neurotrophic factor (GDNF) secretion of two
      glioma cell lines which differ in their invasive phenotypes. Here, we show that
      the high-grade C6 cells are more migrative and secrete more GDNF than the low
      grade Hs683 cells. GDNF signaling is more highly activated in C6 cells than in
      Hs683 cells. Treatment of the Hs683 cells with GDNF significantly increased
      migration comparable to the C6 cells, revealing the autocrine and/or paracrine
      effect of GDNF on promotion of the glioma cell migration. We then examined the
      involvement of mitogen-activated protein kinases (MAPKs) including c-Jun N
      terminal protein kinase (JNK), extracellular signal-regulated kinases (ERKs) and
      p38 MAPK in Hs683 cell migration induced by GDNF. A prominent activation of JNK,
      ERKs and p38 MAPK was observed in the GDNF-treated cells. Functional studies
      showed that the activation of these MAPKs was critical for Hs683 cell migration
      induced by GDNF. Our findings revealing molecular mechanisms for the promoting
      effect of GDNF on glioma cell migration may provide an insight into a better
      understanding to the malignant progression of human gliomas.

PMID- 16814422
TI  - Rabies virus-induced apoptosis involves caspase-dependent and caspase-independent
      pathways.
AB  - Previously, it has been shown that the laboratory attenuated rabies virus CVS
      B2C, but not the wild-type virus SHBRV, induces apoptosis in mice and the
      induction of apoptosis is mediated by viral glycoprotein. Induction of apoptosis
      by CVS-B2C limits the spread of the virus in the CNS. In the present study, we
      characterized the pathways by which CVS-B2C induces apoptosis. BSR cells were
      infected with CVS-B2C or SHBRV and harvested at different time points for
      detection of apoptosis by immunofluorescence and flow cytometry. Apoptosis was
      detected only in cells infected with CVS-B2C, but not SHBRV. Caspase activity and
      expression of several apoptotic proteins were analyzed by fluorometric assay and
      Western blotting. Activation of caspase-8 and -3, but not of caspase-9, was
      observed in CVS-B2C-infected cells. In addition, the level of expression of Apaf
      1 did not change. Furthermore, PARP was cleaved confirming activation of
      downstream caspases. All these data suggest that CVS-B2C infection activates the
      extrinsic, but not the intrinsic, apoptotic pathway. In addition, AIF, a caspase
      independent apoptotic protein was up-regulated and translocated from the
      cytoplasm to the nucleus post-infection, suggesting that apoptosis induced by CVS
      B2C also involves the activation of a caspase-independent pathway.

PMID- 16814423
TI  - Smoking cessation before diagnosis and survival in early stage non-small cell
      lung cancer patients.
AB  - Smoking cessation decreases the risk of lung cancer. However, little is known
      about how smoking cessation affects lung cancer survival. We examined the
      association between smoking cessation and overall survival (OS) and recurrence
      free survival (RFS) in 543 early stage non-small cell lung cancer (NSCLC)
      patients. The data were analyzed using log-rank test and Cox proportional hazard
      models, adjusting for age, gender, stage, and smoking intensity. The median
      follow-up time was 57 months (range 0.2-140 months). There were 191 recurrences
      and 285 deaths. The 5-year OS rates were 50% (95% confidence interval (CI), 43
      58%) for current smokers, 54% (44-65%) for ex-smokers who quit 1-8 years, 59% (49
      70%) for ex-smokers who quit 9-17 years, 58% (47-69%) for ex-smokers who quit >
      or =18 years prior to diagnosis, and 76% (63-90%) for never smokers (P=0.09, log
      rank test). The adjusted hazard ratios for ex-smokers who quit 1-8, 9-17, > or
      =18 years, and never smokers were 0.82 (95% CI, 0.59-1.13), 0.69 (0.49-0.97),
      0.66 (0.45-0.95), and 0.54 (0.29-0.996), respectively, when compared with current
      smokers (P(trend)=0.004). Similar associations were found among ever smokers
      only, when smoking cessation time was treated as a continuous variable, and for
      RFS. The significantly beneficial effects of smoking cessation on OS and RFS were
      observed among women only, while not among men (P=0.01 for interactions between
      gender and smoking cessation). In conclusion, smoking cessation is associated
      with improved survival in early stage NSCLC patients. The longer the time since
      cessation of smoking, the better the survival outcome.

PMID- 16814424
TI  - Genetic screen for signal peptides in Hydra reveals novel secreted proteins and
      evidence for non-classical protein secretion.
AB  - We have screened a Hydra cDNA library for sequences encoding N-terminal signal
      peptides using the yeast invertase secretion vector pSUC [Jacobs et al., 1997. A
      genetic selection for isolating cDNAs encoding secreted proteins. Gene 198, 289
      296]. We isolated and sequenced 907 positive clones; 88% encoded signal peptides;
      12% lacked signal peptides. By searching the Hydra EST database we identified
      full-length sequences for the selected clones. These encoded 37 known proteins
      with signal peptides and 40 novel Hydra-specific proteins with signal peptides.
      Localization of two signal peptide-containing sequences, VEGF and ferritin, to
      the secretory pathway was confirmed with GFP fusion proteins. In addition, we
      isolated 105 clones which lacked signal peptides but which supported invertase
      secretion from yeast. Isolation of plasmids from these clones and
      retransformation in invertase-negative yeast cells confirmed the phenotype. A GFP
      fusion protein of one such clone encoding the foot morphogen pedibin was
      localized to the cytoplasm in transfected Hydra cells and did not enter the
      ER/Golgi secretory pathway. Secretion of pedibin and other proteins lacking
      signal peptides appears to occur by a non-classical protein secretion route.

PMID- 16814425
TI  - The regulation of myosin II in Dictyostelium.
AB  - Dictyostelium conventional myosin (myosin II) is an abundant protein that plays a
      role in various cellular processes such as cytokinesis, cell protrusion and
      development. This review will focus on the signal transduction pathways that
      regulate myosin II during cell movement. Myosin II appears to have two modes of
      action in Dictyostelium: local stabilization of the cytoskeleton by myosin
      filament association to the actin meshwork (structural mode) and force generation
      by contraction of actin filaments (motor mode). Some processes, such as cell
      movement under restrictive environment, require only the structural mode of
      myosin. However, cytokinesis in suspension and uropod retraction depend on motor
      activity as well. Myosin II can self-assemble into bipolar filaments. The
      formation of these filaments is negatively regulated by heavy chain
      phosphorylation through the action of a set of novel alpha kinases and is
      relatively well understood. However, only recently it has become clear that the
      formation of bipolar filaments and their translocation to the cortex are separate
      events. Translocation depends on filamentous actin, and is regulated by a cGMP
      pathway and possibly also by the cAMP phosphodiesterase RegA and the p21
      activated kinase PAKa. Myosin motor activity is regulated by phosphorylation of
      the regulatory light chain through myosin light chain kinase A. Unlike
      conventional light chain kinases, this enzyme is not regulated by calcium but is
      activated by cGMP-induced phosphorylation via an upstream kinase and subsequent
      autophosphorylation.

PMID- 16814426
TI  - From cell-cell adhesion and cellular oscillations to spectacular views inside the
      cell--50 years of research with Dictyostelium.

PMID- 16814427
TI  - Cloning of Dictyostelium eIF6 (p27BBP) and mapping its nucle(ol)ar localization
      subdomains.
AB  - Eukaryotic translation initiation factor 6 (eIF6), also termed p27BBP, is an
      evolutionary conserved regulator of ribosomal function. The protein is involved
      in maturation and/or export from the nucleus of the 60S ribosomal subunit.
      Regulated binding to and release from the 60S subunit also regulates formation of
      80S ribosomes, and thus translation. The protein is also found in hemidesmosomes
      of epithelial cells expressing beta4 integrin and is assumed to regulate cross
      talk between beta4 integrin, intermediate filaments and ribosomes. In the present
      study we show that the Dictyostelium eIF6 (also called p27BBP) gene is expressed
      during growth, down-regulated during the first hours of starvation, and up
      regulated again at the end of aggregation. Phagocytosis, and to a lesser extent
      pinocytic uptake of axenic medium, stimulate gene expression in starving cells.
      The eIF6 gene is present in single copy and its ablation is lethal. We utilized
      the green fluorescent protein (GFT) as fusion protein marker to investigate
      sequences responsible for eIF6 subcellular localization. The protein is found
      both in cytoplasm and nucleus, and is enriched in nucleoli. Deletion sequence
      analysis shows that nucle(ol)ar localization sequences are located within the N-
      and C-terminal subdomains of the protein.

PMID- 16814428
TI  - Selective loss of synaptic proteins in Alzheimer's disease: evidence for an
      increased severity with APOE varepsilon4.
AB  - A pathological feature of Alzheimer's disease (AD) is an area-specific neuronal
      loss that may be caused by excitotoxicity-related synaptic dysfunction. Relative
      expression levels of synaptophysin, dynamin I, complexins I and II, N-cadherin,
      and alphaCaMKII were analysed in human brain tissue from AD cases and controls in
      hippocampus, and inferior temporal and occipital cortices. Synaptophysin and
      dynamin I are presynaptic terminal proteins not specific to any neurotransmitter
      system whereas complexin II, N-cadherin, and alphaCaMKII are specific for
      excitatory synapses. Complexin I is a presynaptic protein localised to inhibitory
      synapses. There were no significant differences in synaptophysin, dynamin I, N
      cadherin, or alphaCaMKII protein levels between AD cases and controls. The
      complexin proteins were both markedly lower in AD cases than in controls (P <
      0.01). Cases were also categorised by APOE genotype. Averaged across areas there
      was a 36% lowering of presynaptic proteins in AD cases carrying at least one
      epsilon4 allele compared with in AD cases lacking the epsilon4 allele. We infer
      that synaptic protein level is not indicative of neuronal loss, but the synaptic
      dysfunction may result from the marked relative loss of the complexins in AD, and
      lower levels of presynaptic proteins in AD cases with the APOE epsilon4 allele.

PMID- 16814429
TI  - Lymphocyte subset patterns and cytokine production in Alzheimer's disease
      patients.
AB  - To investigate the signs of inflammatory processes in Alzheimer's disease (AD),
      we examined peripheral blood mononuclear cells (PBMC) from 51 AD patients (29
      with mild and 22 with moderately severe dementia) and 51 age-matched healthy
      controls (HC), using flow cytometry to analyse the absolute number and the
      percentage of T, B and NK cells. We also studied the surface expression of CD25,
      CD28, CD57, CD71, CD45RA and CD45RO markers on cells CD4+ and CD8+. In 30 AD
      patients and 20 HC the production of IL-2, IFN-gamma, IL-10 and TNF-alpha by PBMC
      after stimulation with [25-35], [1-40] and [1-16] beta-amyloid (betaA) fragments
      was also evaluated. A significant decrease in circulating B and CD8+CD28- cells,
      as well as an increase in CD8+ cells expressing CD71+ and CD28+, was observed in
      AD patients. A significant decrease in IL-10 production was also found after
      stimulation of PMBC with betaA [1-40]. The decreased IL-10 production was not
      related to disease severity. The observed imbalance of immune peripheral cell
      subpopulations and decreased IL-10 production point to a reduction of suppressor
      cell function in AD patients.

PMID- 16814430
TI  - Improved design and intranasal delivery of an M2e-based human influenza A
      vaccine.
AB  - M2 is the third integral membrane protein of influenza A. M2e, the extracellular,
      23 amino acid residues of M2, has been remarkably conserved in all human
      influenza A strains. This prompted us to evaluate the use of M2e as a potential
      broad-spectrum immunogen in a mouse model for influenza infection. Genetic fusion
      of the M2e and hepatitis B virus core (HBc) coding sequences allowed us to obtain
      highly immunogenic virus-like particles. This M2e-HBc vaccine induced complete
      protection in mice against a lethal influenza challenge. Protective immunity was
      obtained regardless of the position of M2e in the M2e-HBc chimera at the amino
      terminus or inserted in the immuno-dominant loop of the HBc protein. Increasing
      the copy number of M2e inserted at the N-terminus from one to three per monomer
      (240-720 per particle) significantly enhanced the immune response and reduced the
      number of vaccinations required for complete protection against a lethal
      challenge with influenza A virus. A series of M2e-HBc constructs was subsequently
      combined with CTA1-DD, a recombinant cholera toxin A1 derived mucosal adjuvant,
      to test its efficacy as an intranasally delivered vaccine. All hybrid VLPs tested
      with CTA1-DD completely protected mice from a potentially lethal infection and,
      in addition, significantly reduced morbidity. Overall, increased resistance to
      influenza challenge in the mice correlated with an enhanced Th1-type M2e-specific
      antibody response induced by vaccination. These results show that M2e is a valid
      and versatile vaccine candidate to protect against any strain of human influenza
      A.

PMID- 16814431
TI  - Single amino acid substitutions in the hemagglutinin of influenza
      A/Singapore/21/04 (H3N2) increase virus growth in embryonated chicken eggs.
AB  - Most of the recently circulating H3N2 influenza A strains do not replicate well
      in embryonated chicken eggs and had to be isolated by cell culture, which
      presents a great challenge for influenza vaccine production using embryonated
      chicken eggs. We previously reported that a human H3N2 virus, A/Fujian/411/02,
      which replicates poorly in eggs, could be improved by changing a minimum of two
      HA residues (G186V/V226I or H183L/V226A). Here, we extended our work to the
      A/Singapore/21/04 strain that was also unable to grow in eggs. We showed that a
      single amino acid substitution of either G186V or A196T in the HA resulted in
      significantly increased virus replication in eggs without affecting virus
      antigenicity.

PMID- 16814432
TI  - Prime-boost immunization using DNA vaccine and recombinant Orf virus protects
      pigs against Pseudorabies virus (Herpes suid 1).
AB  - The present study demonstrates the protective potential of a novel prime-boost
      vaccination strategy of pigs against lethal Pseudorabies virus (PRV; Herpes suid
      1) infection. Animals were primed with Sindbis virus-derived plasmids that
      express viral glycoproteins gC and gD (gC- and gD-pSIN) and subsequently booster
      immunized with Orf virus (ORFV; Parapoxvirus) recombinants expressing gC and gD
      (D1701-VrVgC and -VrVgD). The prime-boost vaccination induced strong humoral and
      cellular-like PRV-specific immune responses. All prime-boost vaccinated pigs
      survived the lethal challenge infection without PRV-specific clinical symptoms
      and presented excellent body weight loss attenuation. Most notably, nasal
      shedding of challenge virus was reduced by more than about 3log(10), clearly
      reducing the risk of infection of non-immunized pigs.

PMID- 16814433
TI  - Costs of congenital rubella syndrome (CRS) in Oman: evidence based on long-term
      follow-up of 43 children.
AB  - As part of the national plan for elimination of rubella and congenital rubella
      syndrome (CRS), Oman established a national registry of CRS cases. As of May
      2005, the registry included 43 surviving CRS cases, with a mean age of 11.9
      years. Clinical examinations found that 84% had ocular defects, 84% had
      auditory/speech defects, 70% had neurological manifestations, and 42% had cardiac
      defects. Lifetime medical, special education, and rehabilitation costs were
      assessed. Using a discount rate of 3%, the average direct lifetime cost per
      surviving CRS patient was estimated at 18,644 US dollars. When including
      predicted lost productivity due to CRS, the average discounted direct and
      indirect lifetime costs per surviving CRS patient amounted to 98,734 US dollars.

PMID- 16814434
TI  - Soluble and glyco-lipid modified baculovirus Plasmodium falciparum C-terminal
      merozoite surface protein 1, two forms of a leading malaria vaccine candidate.
AB  - Recombinant homologues of the Plasmodium merozoite surface protein 1 C-terminus
      are leading blood stage malaria vaccine candidates. MSP1 is anchored to the
      merozoite plasma membrane in vivo by a glycosyl-phosphatidyl-inositol (GPI)
      moiety, implicated in malaria pathology. Two types of recombinant Plasmodium
      falciparum MSP1p19 (PfMSP1p19) expressed in baculovirus/insect cells are
      described here: (1) a soluble, secreted form (PfMSP1p19S) and (2) detergent
      soluble cellular form(s) (PfMSP1p19+A), released from the infected cell surface
      by treatment with GPI specific phosphatidyl-inositol phospholipase C (PI-PLC).
      Soluble and cellular PfMSP1p19 were purified and characterized using SDS-PAGE,
      mass spectrometry (MS), N-terminal amino acid sequencing, gel filtration and
      glycan analyses. Quantitative inositol dosage suggested that surface GPI
      processed entities constituted only 14% of the purified cellular PfMSP1p19+A,
      with GPI unprocessed forms likely recovered in the endoplasmic reticulum.
      Nevertheless, this preparation has dramatic immuno-stimulatory activity to be
      described elsewhere. The interest of these results for both malaria specific and
      generic vaccine development are discussed.

PMID- 16814435
TI  - Social incompetence in children with ADHD: possible moderators and mediators in
      social-skills training.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) often encounter
      problems in social interactions with peers and are confronted with peer rejection
      and social isolation. The most common approach to social problems in children is
      social skills training. This intervention concept represents a variable mixture
      of cognitive-behavioral intervention elements. In this article the outcome of
      social skills training (SST) for children with ADHD is reviewed. Four
      experimental SSTs are detected and analyzed for potential mediators and
      moderators of treatment efficacy. Candidate mediators (social cognitive skills,
      parenting style and medication-induced reduction of key symptoms) are discussed
      within an empirical and theoretical context. Candidate moderators (subtype,
      comorbidity, gender and age) are evaluated for their empirical support. It is
      argued that, although fragmented, there is ample evidence and knowledge to adapt
      the SST-paradigm towards the specific needs of children suffering from ADHD and
      to guide future research towards more effective, "well established"
      interventions.

PMID- 16814436
TI  - The association between awareness deficits and rehabilitation outcome following
      acquired brain injury.
AB  - The relationship between awareness of deficits and rehabilitation outcome
      following acquired brain injury (ABI) has yet to be established. The aim of the
      present review was to examine empirical evidence concerning the issue of whether
      awareness of deficits is necessary for rehabilitation gains and provide
      guidelines to assist clinical decision-making. The search strategy entailed
      identification of longitudinal group outcome studies with individuals who had
      experienced ABI of varying aetiology published between 1980 and 2006 in which
      awareness of deficits was systematically measured from the outset of
      rehabilitation and examined in relation to post-intervention functional outcomes.
      Eligible studies were evaluated against indicators of methodological quality. The
      review yielded 12 empirical studies, of which four indicated that individuals
      with greater awareness of deficits achieve more favorable rehabilitation outcomes
      and six provided partial support for this association. Two studies failed to
      support this view. Overall, the key issues requiring consideration when forming
      opinions and developing interventions for individuals with awareness deficits
      include the following: (a) how awareness is conceptualized and determined; (b)
      the perceived impact of poor self-awareness and possible adverse effects of
      targeting awareness; (c) biopsychosocial factors underlying awareness deficits;
      (d) the clients' goals and expectations in the intervention; and (e) the scope,
      intensity and resources of the rehabilitation context. Clinical recommendations
      are made regarding the circumstances in which it might be optimal to target the
      development of awareness in the context of rehabilitation.

PMID- 16814437
TI  - Risk assessment for creatine monohydrate.
AB  - Creatine monohydrate (creatine) has become an increasingly popular ingredient in
      dietary supplements, especially sports nutrition products. A large body of human
      and animal research suggests that creatine does have a consistent ergogenic
      effect, particularly with exercises or activities requiring high intensity short
      bursts of energy. Human data are primarily derived from three types of studies:
      acute studies, involving high doses (20 g/d) with short duration (< or = 1 week),
      chronic studies involving lower doses (3-5 g/d) and longer duration (1 year), or
      a combination of both. Systematic evaluation of the research designs and data do
      not provide a basis for risk assessment and the usual safe Upper Level of Intake
      (UL) derived from it unless the newer methods described as the Observed Safe
      Level (OSL) or Highest Observed Intake (HOI) are utilized. The OSL risk
      assessment method indicates that the evidence of safety is strong at intakes up
      to 5 g/d for chronic supplementation, and this level is identified as the OSL.
      Although much higher levels have been tested under acute conditions without
      adverse effects and may be safe, the data for intakes above 5 g/d are not
      sufficient for a confident conclusion of long-term safety.

PMID- 16814438
TI  - Risk assessment for coenzyme Q10 (Ubiquinone).
AB  - Coenzyme Q10 (CoQ10) widely occurs in organisms and tissues, and is produced and
      used as both a drug and dietary supplement. Increasing evidence of health
      benefits of orally administered CoQ10 are leading to daily consumption in larger
      amounts, and this increase justifies research and risk assessment to evaluate the
      safety. A large number of clinical trials have been conducted using a range of
      CoQ10 doses. Reports of nausea and other adverse gastrointestinal effects of
      CoQ10 cannot be causally related to the active ingredient because there is no
      dose-response relationship: the adverse effects are no more common at daily
      intakes of 1200 mg than at a 60 mg. Systematic evaluation of the research designs
      and data do not provide a basis for risk assessment and the usual safe upper
      level of intake (UL) derived from it unless the newer methods described as the
      observed safe level (OSL) or highest observed intake (HOI) are utilized. The OSL
      risk assessment method indicates that the evidence of safety is strong at intakes
      up to 1200 mg/day, and this level is identified as the OSL. Much higher levels
      have been tested without adverse effects and may be safe, but the data for
      intakes above 1200 mg/day are not sufficient for a confident conclusion of
      safety.

PMID- 16814439
TI  - Risk assessment for the carotenoids lutein and lycopene.
AB  - Lutein and lycopene, two prevalent carotenoids in the human diet have become
      increasingly popular ingredients in dietary supplements. A large body of human
      and animal research suggests that oral forms of these carotenoids may provide
      benefits in the areas of eye, prostate, skin and cardiovascular health. The
      increased awareness and use of these ingredients in dietary supplements warrants
      a comprehensive review of their safety. Systematic evaluation of the research
      designs and data provide a basis for risk assessment and the usual tolerable
      Upper Level of Intake (UL) derived from it if the newer methods described as the
      Observed Safe Level (OSL) or Highest Observed Intake (HOI) are utilized. The OSL
      risk assessment method indicates that the evidence of safety is strong at intakes
      up to 20mg/d for lutein, and 75 mg/d for lycopene, and these levels are
      identified as the respective OSL. Although much higher levels have been tested
      without adverse effects and may be safe, the data for intakes above these levels
      are not sufficient for a confident conclusion of long-term safety.

PMID- 16814440
TI  - Evaluation of the toxic potentials of a new camptothecin anticancer agent CKD-602
      on fertility and early embryonic development in rats.
AB  - This study examined the potential adverse effects of a new camptothecin
      anticancer agent, CKD-602, on the fertility and early embryonic development of
      Sprague-Dawley rats. Ninety-six rats of each gender were divided into four
      groups: three treatment groups and a control group. CKD-602 was administered
      intravenously to male rats at 0, 4.7, 14, and 42 microg/kg from 63 days prior to
      mating until the end of the mating period, and to female rats from 14 days before
      mating until day 6 of gestation. All the males were sacrificed after the end of
      the 14-day mating period, while all the females were subjected to a caesarean
      section on day 15 of gestation. In the high dose group, a high incidence of hair
      loss was observed in both genders. A decrease in the level of food consumption,
      followed by a decrease in body weight gain was also observed in both genders. At
      the scheduled necropsy, the gross postmortem examinations revealed an increase in
      the incidence of thymic atrophy, paleness of the thoracic and abdominal organs in
      both genders and an increase in the serum testosterone concentration. In
      addition, there was a decrease in the thymus weight of the males and an increase
      in the liver, spleen, kidneys, lung, and heart weights of the females. There was
      an increase in the number of fetal deaths and post-implantation losses as well as
      a decrease in the litter size found at the caesarean section of the dams. No
      treatment-related effect on the histopathological findings, sexual cycle, pre
      coital time, mating index, fertility index, pregnancy index, and sperm parameters
      was observed. There were no adverse effects on the general findings and
      reproductive performance of the parent animals and early embryonic development in
      the low and medium dose groups. Overall, the no-observed-adverse-effect levels
      (NOAELs) of CKD-602 are believed to be 14 microg/kg for both general toxicity and
      early embryonic development, and more than 42 microg/kg for the reproductive
      performance of the parent animals.

PMID- 16814441
TI  - Still a difficult business? Negotiating alcohol-related problems in general
      practice consultations.
AB  - This paper describes general practitioners' (GPs) experiences of detecting and
      managing alcohol and alcohol-related problems in consultations. We undertook
      qualitative research in two phases in the North-East of England. Initially,
      qualitative interviews with 29 GPs explored their everyday work with patients
      with alcohol-related issues. We then undertook group interviews--two with GPs and
      one with a primary care team--where they discussed and challenged findings of the
      interviews. The GPs reported routinely discussing alcohol with patients with a
      range of alcohol-related problems. GPs believed that this work is important, but
      felt that until patients were willing to accept that their alcohol consumption
      was problematic they could achieve very little. They tentatively introduced
      alcohol as a potential problem, re-introduced the topic periodically, and then
      waited until the patient decided to change their behaviour. They were aware that
      they could identify and manage more patients. A lack of time and having to work
      with the multiple problems that patients brought to consultations were the main
      factors that stopped GPs managing more risky drinkers. Centrally, we compared the
      results of our study with [Thom, B., & Tellez, C. (1986). A difficult business
      Detecting and managing alcohol-problems in general-practice. British Journal of
      Addiction, 81, 405-418] seminal study that was undertaken 20 years ago. We show
      how the intellectual, moral, emotional and practical difficulties that GPs
      currently face are quite similar to those faced by GPs from 20 years ago. As the
      definition of what could constitute abnormal alcohol consumption has expanded, so
      the range of consultations that they may have to negotiate these difficulties in
      has also expanded.

PMID- 16814442
TI  - The auditory-evoked N2 and P3 components in the stop-signal task: indices of
      inhibition, response-conflict or error-detection?
AB  - The N2 and P3 components have been separately associated with response inhibition
      in the stop-signal task, and more recently, the N2 has been implicated in the
      detection of response-conflict. To isolate response inhibition activity from
      early sensory processing, the present study compared processing of the stop
      signal with that of a task-irrelevant tone, which subjects were instructed to
      ignore. Stop-signals elicited a larger N2 on failed-stop trials and a larger P3
      on successful-stop trials, relative to ignore-signal trials, likely reflecting
      activity related to failed and successful stopping, respectively. ERPs between
      fast and slow reaction-time (RT) groups were also examined as it was hypothesised
      that greater inhibitory activation to stop faster responses would manifest in the
      component reflecting this process. Successful-stop P3 showed the anticipated
      effect (globally larger amplitude in the fast than slow RT group), supporting its
      association with the stopping of an ongoing response. In contrast, N2 was larger
      in the slow than fast RT group, and in contrast to the predictions of the
      response-conflict hypothesis, successful-stop N2 and the response-locked error
      negativity (Ne) differed in scalp distribution. These findings indicate that the
      successful-stop N2 may be better explained as a deliberate form of response
      control or selection, which the slow RT group employed as a means of increasing
      the likelihood of a successful-stop. Finally, a comparison of stimulus and
      response-locked ERPs revealed that the failed-stop N2 and P3 appeared to reflect
      error-related activity, best observed in the response-locked Ne and error
      positivity (Pe). Together these findings indicate that the successful-stop N2 and
      P3 reflect functionally distinct aspects of response control that are dependent
      upon performance strategies, while failed-stop N2 and P3 reflect error-related
      activity.

PMID- 16814443
TI  - Antimutagenic effect of essential oil of sage (Salvia officinalis L.) and its
      monoterpenes against UV-induced mutations in Escherichia coli and Saccharomyces
      cerevisiae.
AB  - Mutagenic and antimutagenic potential of essential oil (EO) of cultivated sage
      (S. officinalis L.) and its monoterpenes: thujone, 1,8-cineole, camphor and
      limonene against UVC-induced mutations was studied with Salmonella/microsome, E.
      coli WP2, E. coli K12 [Simic, D., Vukovic-Gacic, B., Knezevic-Vukcevic, J., 1998.
      Detection of natural bioantimutagens and their mechanisms of action with
      bacterial assay-system. Mutat. Res. 402, 51-57] and S. cerevisiae D7 reversion
      assays. The toxicity of EO differed, depending on the strain used. The most
      sensitive were permeable strains TA100, TA102, E. coli K12 IB112 and non
      permeable WP2. Mutagenic potential of EO and monoterpenes was not detected, with
      or without S9. EO reduced the number of UV-induced revertants in a concentration
      dependent manner, reaching 50-70% of inhibition at the maximum non-toxic
      concentrations: 3 microl/plate (TA102), 5 microl/plate (WP2), 7.5 microl/plate
      (IB112), 30 microl/plate (E. coli K12 SY252) and 60 microl/plate (D7). The
      metabolic activation had no effect on antimutagenic potential of EO. Similar
      toxicity of monoterpenes was observed in TA100, E. coli SY252 and D7, with the
      exception of limonene (less toxic to D7). Reduction of UV-induced revertants by
      non-toxic concentrations of monoterpenes, tested with SY252 and D7, reached 40
      50% at 15-20 microl/plate of thujone, 10 microl/plate of cineole and 1-10
      microg/plate of camphor. Limonene showed antimutagenic effect only in D7. Our
      data recommend sage monoterpenes for further chemoprevention studies.

PMID- 16814444
TI  - Immediate oxygen therapy prevents brain cell injury in carbon monoxide poisoned
      rats without loss of consciousness.
AB  - In CO-poisoned patients without loss of consciousness no significant long-term
      functional differences in outcome have been shown in any hyperbaric versus
      normobaric oxygen studies. Since brain histology changes cannot be studied in CO
      poisoned patients we evaluated the efficacy of normobaric and hyperbaric oxygen
      therapy in preventing brain cell injury in CO-poisoned animals without loss of
      consciousness. Wistar rats without loss of consciousness after exposure to
      3000ppm of CO for 60min were exposed to ambient air (group 1), 100% oxygen at a
      pressure of 1bar (group 2) and 100% oxygen at a pressure of 3bar (group 3). The
      rats were sacrificed after two weeks, brain samples were stained with hematoxylin
      eosin and a percentage of pyknotic cells in hippocampus was reported. Analyses of
      differences in percentage of pyknotic cells between different kinds of therapy
      showed that the percentage of pyknotic cells of the second group (2.3+/-1.2%)
      treated with normobaric oxygen and the third group (4.5+/-4.0%) treated with
      hyperbaric oxygen were similar, and both of them were significantly different,
      with a much lower percentage of pyknotic cells, from the first group left on
      ambient air (47.7+/-10.0%). In conclusion, immediate normobaric and hyperbaric
      oxygen therapy equally prevents hippocampal cell injury in CO-poisoned rats
      without loss of consciousness.

PMID- 16814445
TI  - Incidence of sudden cardiac arrest is higher in areas of low socioeconomic
      status: a prospective two year study in a large United States community.
AB  - BACKGROUND: A potential effect of socioeconomic status on occurrence of sudden
      cardiac arrest in the community is likely, but has not been evaluated fully.
      METHODS: All cases of sudden cardiac arrest in Multnomah County Oregon
      (population 660,486; February 2002-January 2004) were identified prospectively
      and categorized by census tract based on the address of residence and specific
      geographic location of occurrence of cardiac arrest. Each census tract was
      assigned to quartiles of median income, poverty level, median home value, and
      educational attainment. RESULTS: Of 714 cases (annual incidence 54 per 100,000),
      697 (98%) had residential addresses that matched a county census tract
      successfully. For each socioeconomic status measure, the incidence of cardiac
      arrest was 30-80% higher in the lowest compared to the highest socioeconomic
      status census tracts. Annual incidence in census tracts in the lowest compared to
      the highest quartiles of median home value was 60.5 versus 35.1 per 100,000 (RR
      1.7, 95% CI 1.4-2.2). This gradient was exaggerated significantly for age<65
      years (34.5 versus 15.1 per 100,000, RR 2.3, 95% CI 1.6-3.3). Identical trends
      were observed for sudden cardiac arrest based on location, with 60% of all cases
      and 66% of cases age<65 years occurring in the two quartiles with lowest
      socioeconomic status. CONCLUSIONS: Low neighborhood socioeconomic status was
      associated with a significantly higher incidence of sudden cardiac arrest based
      on address of residence as well as location of cardiac arrest. For effective
      deployment of strategies for community-based prevention such as the automated
      external defibrillator, neighborhood socioeconomic status is likely to be an
      important consideration.

PMID- 16814446
TI  - Prehospital transcutaneous cardiac pacing for symptomatic bradycardia or
      bradyasystolic cardiac arrest: a systematic review.
AB  - BACKGROUND: Advanced cardiac life support (ACLS) guidelines suggest
      transcutaneous cardiac pacing (TCP) for the treatment of symptomatic bradycardia
      (SB) and bradyasystolic cardiac arrest (BACA). Many EMS systems are extrapolating
      these guidelines and employing TCP in the prehospital setting. Our objective was
      to conduct a systematic review to determine the efficacy of prehospital TCP in
      the management of these two conditions. METHODS: MEDLINE (1966-2004), EMBase and
      Science Citation Index (1980-2004) were searched using: prehospital/emergency
      medical services; external/transcutaneous; pacing. Two reviewer teams blinded to
      the source and author conducted a hierarchical selection (title, abstract,
      article) and quality assessment using a validated scale. Kappa agreement at each
      level of review was measured. Data abstraction was done by consensus. RESULTS:
      Thirty-four articles were identified and seven selected (Kappa agreement; title:
      0.85, abstract: 0.78, full article: 0.82). Article quality was poor in all
      trials. There were three case series (BACA, n=215), three unblinded randomised
      controlled trials (one BACA, two BACA+SB), and one subgroup (SB) analysis. In the
      case series of paced BACA patients, 0/215 survived to hospital discharge. In the
      BACA trials 16/509 (paced) versus14/497 (control) survived to discharge. In a
      subgroup of one SB trial 5/6 (paced) versus 1/7 (control) survived to discharge
      (p=0.01). When a SB trial subgroup was combined with a case series 4/27 (paced)
      versus 0/24 (control) survived to discharge (p=0.07). CONCLUSIONS: In the
      prehospital setting, there is no evidence to support the use of TCP in
      bradyasystolic cardiac arrest. There is inadequate evidence to determine the
      efficacy of prehospital TCP in the treatment of symptomatic bradycardia.

PMID- 16814447
TI  - Resuscitation by primary care doctors.
AB  - BACKGROUND: Sudden cardiac arrest is a common mechanism of premature death in the
      community. Resuscitation is often possible, but no large study of resuscitation
      by doctors who practice there has been published. METHODS: General practitioners
      (GPs) equipped with defibrillators reported 555 patients with cardiac arrest in
      whom they attempted resuscitation. FINDINGS: Average age was 65.4, 75% male. Most
      arrests (49%) occurred at the patient's home but some (18%) occurred at or near
      the doctors' surgeries. Heart disease was responsible for 88% of the arrests: in
      these cases resuscitation to leave hospital alive was frequently successful (148
      of 436 attempts, 34%). Success was rare (one of 59, <2%) when the arrest was due
      to non-cardiac disease. Resuscitation was most common when the first monitored
      rhythm was shockable (VF/VT) and defibrillated promptly: 144 out of 351 (41%)
      patients surviving. VF/VT was most common with early rhythm monitoring,
      particularly when the doctor was present (63% survival), or nearby (54%). When
      VF/VT complicated AMI, 72% of those defibrillated within 1min of onset survived.
      With delayed attendance, the frequency of VF/VT fell and asystole or Pulseless
      Electrical Activity (PEA) became more common. Survival after resuscitation was
      rare for patients presenting with these rhythms: five of 202 (2.5%). No such
      patient survived unless the rhythm could be converted to VF/VT with drugs or
      basic life support and subsequently shocked. CONCLUSION: Primary care doctors
      equipped with defibrillators attend patients with cardiac arrest under
      circumstances in which resuscitation is frequently successful. This presents a
      unique opportunity to reduce mortality from sudden cardiac arrest.

PMID- 16814448
TI  - Language outside the focus of attention: the mismatch negativity as a tool for
      studying higher cognitive processes.
AB  - Which aspects of language and cognitive processing take place irrespective of
      whether subjects focus their attention on incoming stimuli and are, in this
      sense, automatic? The Mismatch Negativity (MMN), a neurophysiological brain
      response recorded in the EEG and MEG, is elicited by attended and unattended
      stimuli alike. Recent studies investigating the cognitive processes underlying
      spoken language processing found that even under attentional withdrawal, MMN size
      and topography reflect the activation of memory traces for language elements in
      the human brain. Familiar sounds of one's native language elicit a larger MMN
      than unfamiliar sounds, and at the level of meaningful language units, words
      elicit a larger MMN than meaningless pseudowords. This suggests that the MMN
      reflects the activation of memory networks for language sounds and spoken words.
      Unattended word stimuli elicit an activation sequence starting in superior
      temporal cortex and rapidly progressing to left-inferior-frontal lobe. The spatio
      temporal patterns of cortical activation depend on lexical and semantic
      properties of word stems and affixes, thus indicating that the MMN can give clues
      about lexico-semantic information processing stored in long term memory. At the
      syntactic level, MMN size was found to reflect whether a word string conforms to
      abstract grammatical rules. This growing body of results suggests that lexical,
      semantic and syntactic information can be processed by the central nervous system
      outside the focus of attention in a largely automatic manner. Analysis of spatio
      temporal patterns of generator activations underlying the MMN to speech may be an
      important tool for investigating the brain dynamics of spoken language processing
      and the activated distributed cortical circuits acting at long-term memory
      traces.

PMID- 16814449
TI  - A comparison of the effects of sequential transdermal versus continuous orally
      administered hormone replacement therapies on plasma total homocysteine levels in
      postmenopausal women: a randomized, placebo-controlled study.
AB  - OBJECTIVE: The objective was to determine the effects of transdermal and oral
      hormone replacement therapies on plasma total homocysteine levels in
      postmenopausal women. MATERIAL AND METHODS: One hundred and ten postmenopausal
      patients were enrolled in the study. Participants were randomized into three
      groups: in Group A (n = 31) oral continuous combined therapy and in Group B (n =
      30) transdermal sequential hormone replacement therapy were given for 6 months. A
      placebo was administered orally to the control group (Group C, n = 30). Serum
      homocysteine levels were studied prior to and after 6 months of treatment in all
      groups. RESULTS: There were no statistical significant differences in mean serum
      homocysteine levels among the groups prior to the study. The mean homocysteine
      levels after 6 months in Groups A-C were also similar. CONCLUSIONS: Serum
      homocysteine levels alter with neither oral continuous nor sequential transdermal
      hormone replacement therapy.

PMID- 16814450
TI  - Human papillomavirus (HPV) infections as risk factors for cytological and
      histological abnormalities in baseline PAP smear-negative women followed-up for 2
      years in the LAMS study.
AB  - OBJECTIVE: To assess the role of HPV as determinant of the incident cytological
      abnormalities (SIL) and cervical lesions (CIN) during a 24-month follow-up of
      baseline PAP smear-negative subgroup of women included in the Latin American
      Screening study (LAMS). STUDY DESIGN: A group of 365 women with normal Pap smear
      and negative or positive high-risk Hybrid Capture II test were prospectively
      followed-up for 24 months at Campinas and Sao Paulo (Brazil). The incidence rate
      (IR) and risk ratio (RR and 95% CI) of developing cytological or histological
      abnormality during the follow-up was calculated for HPV-negative and HPV-positive
      women. RESULTS: During the 12-month follow-up, women HPV-positive at baseline had
      developed a significantly higher rate of incident LSIL (IR=3.5%, RR=1.4; 95% CI
      1.1-1.7) and HSIL (IR=0.7%, RR=1.5; 95% CI 1.4-1.7) abnormality. For HSIL, the IR
      increased to 2.1% and the RR increased to 1.7 (95% CI 1.5-1.9) among those
      followed for 24 months. Similarly, women with positive HPV tests were at a higher
      risk of developing CIN 2-3 (IR=2.6%, RR=1.5; 95% CI 1.4-1.6) during the first 12
      months of follow-up, and for those followed for 24 months, this RR increased
      further to 1.7 (95% CI 1.5-1.9) although the IR was 0.7%. CONCLUSIONS: Oncogenic
      HPV infections comprise a significant risk factor for incident cervical
      abnormalities, and HPV test is a useful adjunct to cytology in detecting the high
      risk patients among baseline PAP smear-negative women.

PMID- 16814451
TI  - Pentacoordinate and hexacoordinate ferric hemes in acid medium: EPR, UV-Vis and
      CD studies of the giant extracellular hemoglobin of Glossoscolex paulistus.
AB  - The equilibrium complexity involving different axially coordinated hemes is
      peculiar to hemoglobins. The pH dependence of the spontaneous exchange of ligands
      in the extracellular hemoglobin from Glossoscolex paulistus was studied using UV
      Vis, EPR, and CD spectroscopies. This protein has a complex oligomeric assembly
      with molecular weight of 3.1 MDa that presents an important cooperative effect. A
      complex coexistence of different species was observed in almost all pH values,
      except pH 7.0, where just aquomet species is present. Four new species were
      formed and coexist with the aquomethemoglobin upon acidification: (i) a "pure"
      low-spin hemichrome (Type II), also called hemichrome B, with an usual spin state
      (d(xy))(2)(d(xz),d(yz))(3); (ii) a strong g(max) hemichrome (Type I), also
      showing an usual spin state (d(xy))(2)(d(xz),d(yz))(3); (iii) a hemichrome with
      unusual spin state (d(xz),d(yz))(4)(d(xy))(1) (Type III); (iv) and a high-spin
      pentacoordinate species. CD measurements suggest that the mechanism of species
      formation could be related with an initial process of acid denaturation. However,
      it is worth mentioning that based on EPR the aquomet species remains even at
      acidic pH, indicating that the transitions are not complete. The "pure" low-spin
      hemichrome presents a parallel orientation of the imidazole ring planes but the
      strong g(max) hemichrome is a HALS (highly anisotropic low-spin) species
      indicating a reciprocally perpendicular orientation of the imidazole ring planes.
      The hemichromes and pentacoordinate formation mechanisms are discussed in detail.

PMID- 16814452
TI  - Performance of a stratified sand filter in removal of chemical oxygen demand,
      total suspended solids and ammonia nitrogen from high-strength wastewaters.
AB  - A stratified sand filter column, operated in recirculation mode and treating
      synthetic effluent resembling high-strength dairy wastewaters was studied over a
      342-d duration. The aim of this paper was to examine the organic, total suspended
      solids (TSS) and nutrient removal rates of the sand filter, operated in
      recirculation mode, under incrementally increasing hydraulic and organic loading
      rates and to propose a field filter-sizing criterion. Best performance was
      obtained at a system hydraulic loading rate of 10 L m(-2) d(-1); a higher system
      hydraulic loading rate (of 13.4 L m(-2) d(-1)) caused surface ponding. The system
      hydraulic loading rate of 10 L m(-2) d(-1) gave a filter chemical oxygen demand
      (COD), TSS, and total kjeldahl nitrogen (TKN) loading rate of 14, 3.7, and 2.1 g
      m(-2) d(-1), respectively, and produced consistent COD and TSS removals of
      greater than 99%, and an effluent NO(3)-N concentration of 42 mg L(-1)
      (accounting for an 86% reduction in total nitrogen (Tot-N)). As the proportional
      surface area requirement for the sand filter described in this study is less than
      the recommended surface area requirement of a free-water surface (FWS) wetland
      treating an effluent of similar quality, it could provide an economic and
      sustainable alternative to conventional wetland treatment.

PMID- 16814453
TI  - Locating Escherichia coli contamination in a rural South Carolina watershed.
AB  - One of the problems associated with the use of ambient water quality standards in
      surface water regulation is the difficulty of identifying and regulating nonpoint
      source pollution, making such standards unenforceable, especially at the local
      level. We used the Escherichia coli indicator to locate the most contaminated
      reaches in rural South Carolina's Bush River watershed (297 km(2), 186 stream
      km). We divided the watershed into 20 smaller reaches and sampled each reach
      multiple times, but restricted each sampling round to one day. We located four
      low order creek reaches, representing just nine stream-km, where we observed
      geometric mean E. coli densities of over 1250 E. coli/100 mL; in each case, the
      source of the contamination (riparian grazing of cattle) was easily identifiable.
      On the Bush River itself, we observed a step change in one reach where geometric
      means increased from 106 E. coli/100 mL to 565 E. coli/100 mL over the reach's 10
      km length. In this case, the sources of contamination were not as obvious as in
      the lower order streams; in this case, more advanced Microbial Source Tracking
      techniques will be required to identify the sources. Nevertheless, this sampling
      protocol helped locate polluted reaches and provided decision-makers with
      reasonable justifications for concrete action in deciding where (or where not) to
      install conservation practices and where more sophisticated (and expensive) MST
      techniques were warranted.

PMID- 16814454
TI  - Decolorization of triphenylmethane dye-bath effluent in an integrated two-stage
      anaerobic reactor.
AB  - In the present study, decolorization of a simulated dye waste containing three
      different triphenylmethane (TPM) dyes--Magenta, Malachite Green and Crystal
      Violet, was investigated in a laboratory scale, two-stage anaerobic high-rate
      reactor. The effect of various parameters (influent dye concentration, hydraulic
      and co-substrate loading rates) on color and COD removal efficiency of the
      reactor has been studied. It has been shown that the influent dye concentration
      had little effect on overall COD and color removal efficiency. More than 99%
      color removal and 96% COD removal efficiency were maintained even at a dye
      concentration of 500 mg/l and a dye loading rate of 1000 mg/l day. However, a
      minimum level of glucose as supplementary carbon source is required to maintain
      the maximum color removal efficiency and it drops appreciably when no glucose is
      added to the influent. The study also showed that the acidogenic phase of the
      reaction plays an important role in decolorization of the TPM dyes. In addition,
      the two-stage anaerobic reactor was observed to have distinct advantages over the
      single-stage system, as the drop in color and COD removal efficiency of stage 1
      are adequately compensated by stage 2 of the reactor especially under high dye
      loading rates accompanied by low co-substrate loading and under reduced HRTs.

PMID- 16814455
TI  - Nerve distribution along the prostatic capsule.
AB  - OBJECTIVES: Recent literature describes indications for a more-complex course of
      fibres of the neurovascular bundle (NVB), despite the widely held assumption that
      it is gathered at the rectolateral side of the prostate. The objective of this
      study therefore was to determine the typical pattern of nerve distribution along
      the prostatic capsule. MATERIALS AND METHODS: Permanent sections of 31 patients,
      who underwent non-nerve-sparing radical prostectomy (RP) at our institution, were
      investigated. A total of 186 slides taken from the apex, mid-part, and base of
      the prostate was analyzed by microscopy. Before microscopy, slides were divided
      into 12 sectors and numbered clockwise starting from "1" for left ventral sides
      to "6" for the rectal sides (accordingly, "12"-"7" for right half). Every single
      nerve and ganglion in the prostatic capsule and the periprostatic tissue was
      counted in each sector. RESULTS: The majority of nerves found in the sectors
      corresponded to the typical location of the NVB at the rectolateral sides of the
      prostate (4/5 or 8/9 o'clock sectors). In these two sectors, a median of 45.9
      65.6% of counted nerves per half was found. However, a significant amount of
      nerves (21.5%-28.5%) was detected above the horizontal line. CONCLUSIONS: We
      conclude that 1/5-1/4 of nerves can be found along the ventral circumference of
      the prostatic capsule. To preserve a maximum number of nerves, we therefore
      recommend a modification of the surgical technique by focusing on a high incision
      for nerve sparing on the ventral parts of the prostate.

PMID- 16814456
TI  - Diagnosis of contralateral testicular intraepithelial neoplasia (TIN) in patients
      with testicular germ cell cancer: systematic two-site biopsies are more sensitive
      than a single random biopsy.
AB  - OBJECTIVES: Searching for testicular intraepithelial neoplasia (TIN; carcinoma in
      situ) in the contralateral testis of patients with germ cell tumour (GCT) may
      early disclose contralateral GCT. A single biopsy of the testis is thought to
      accurately detect TIN. Reports on false-negative biopsies have challenged this
      view. We investigated whether systematic two-site biopsies are more sensitive
      than single biopsies. We also studied the prevalence of contralateral TIN in a
      large patient sample. METHODS: A total of 2318 patients with testicular GCT
      underwent contralateral double biopsy. All of the biopsy pairs were examined
      histologically for spermatogenesis and for presence of TIN. Statistical analysis
      involved first, overall prevalence of contralateral TIN; second, associations of
      clinical factors with TIN; third, frequency of discordant findings regarding TIN
      among biopsy pairs; and finally, associations of discordance with clinical
      factors. RESULTS: A total of 119 patients (5.13%; 95% confidence interval [CI],
      4.27-6.11) had contralateral TIN. TIN is associated with poor spermatogenesis
      (relative risk [RR] 15.74; 95%CI, 10.38-23.86) and with testicular atrophy (RR
      3.78). According to TIN, 31.1% of biopsy pairs were discordant. Discordance was
      significantly less frequent in atrophic testes and in patients with poor
      spermatogenesis. CONCLUSIONS: We confirmed the prevalence of contralateral TIN to
      be about 5%. TIN is significantly associated with poor spermatogenesis and with
      testicular atrophy. The diagnostic extra yield imparted by double biopsies is
      18%. Discordant results regarding TIN are predominantly encountered in normal
      sized testicles. The new standard in diagnosing TIN is two-site biopsy.

PMID- 16814457
TI  - Puigvert: a man with a vision-nephron-sparing surgery 30 years ago in Europe.

PMID- 16814458
TI  - Hypoxia-inducible factor 1alpha expression in renal cell carcinoma analyzed by
      tissue microarray.
AB  - OBJECTIVES: Angiogenesis is important for tumour progression and metastatic
      spread. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a major factor regulating
      a number of other angiogenic factors. Renal cell carcinoma (RCC) is a malignancy
      with a variable clinical course, partly attributable to specific genetic
      alterations of the different RCC types. We therefore analysed HIF-1alpha
      expression using immunohistochemistry and related the results to RCC type and
      clinicopathologic variables. MATERIAL AND METHODS: We semiquantitatively analysed
      HIF-1alpha expression using immunohistological staining of a prepared tissue
      microarray. There were 216 patients including 176 conventional, 26 papillary, and
      14 chromophobe RCCs. RESULTS: The HIF-1alpha staining was found mainly in the
      cytoplasm. The tumours were subdivided into HIF-1alpha(LOW) and HIF-1alpha(HIGH)
      on the basis of staining intensity. HIF-1alpha expression between the RCC types
      did not differ. Patients with conventional RCC showed a trend (p=0.055) towards a
      prolonged survival for those with HIF-1alpha(HIGH)-staining versus HIF
      1alpha(LOW)-staining tumors. In conventional RCC there were significant
      differences in HIF-1alpha expression in relation to TNM stage, nuclear grade, and
      vein invasion. In patients with papillary RCC, difference in HIF-1alpha
      expression was observed only for nuclear grade. CONCLUSIONS: We studied HIF
      1alpha expression in RCC using tissue microarray. In patients with conventional
      RCC, HIF-1alpha levels were significantly lower in locally aggressive tumors
      versus localized tumors, and patients with high HIF-1alpha levels tended to have
      a better prognosis. There seems to be a diverging regulation of angiogenesis
      between the different RCC types. Further studies of HIF and angiogenesis in RCC
      are encouraged.

PMID- 16814459
TI  - Relationship between lung cancer and human papillomavirus in north of Iran,
      Mazandaran province.
AB  - Lung cancer is a major health problem and the leading cause of cancer deaths in
      the world. The pathogenesis of lung cancer is complex, and is believed to be due
      to the interaction between environmental and genetic factors. Various evidences
      show that HPV might be involved in bronchial carcinogenesis. In this study, 141
      lung cancer patients and 92 non-cancer control subjects were enrolled to examine
      whether HPV DNA existed in lung tumor and normal tissues in Mazandaran, north
      part of Iran by nested PCR. Our data showed that 33 of 129 lung tumors had HPV
      DNA compared with 8 of 90 non-cancer control subjects (25.6% vs. 9.0%, P=0.002).
      The infection of HPV had an OR of 3.48 (95% CI 1.522-7.958; P=0.002). Meanwhile
      infection of high risk HPV types (16 and 18) had a significantly high OR of lung
      cancer incidence as 8.00 (95% CI 1.425-44.920; P=0.021) compared with 4.423 (95%
      CI 2.407-8.126; P0.0001) of smoking status. This result suggests that HPV
      infection is associated with lung cancer development in Mazandaran, Iran.

PMID- 16814460
TI  - DNA viruses in human cancer: an integrated overview on fundamental mechanisms of
      viral carcinogenesis.
AB  - The first experimental data suggesting that neoplasm development in animals might
      be influenced by infectious agents were published in the early 1900s. However,
      conclusive evidence that DNA viruses play a role in the pathogenesis of some
      human cancers only emerged in the 1950s, when Epstein-Barr virus (EBV) was
      discovered within Burkitt lymphoma cells. Besides EBV, other DNA viruses
      consistently associated with human cancers are the hepatitis B virus (HBV), human
      papillomavirus (HPV), and Kaposi sarcoma herpesvirus (KSHV). Although each virus
      has unique features, it is becoming clearer that all these oncogenic agents
      target multiple cellular pathways to support malignant transformation and tumor
      development.

PMID- 16814461
TI  - Characterization of naphtho[1,2-a]pyrene and naphtho[1,2-e]pyrene DNA adducts in
      C3H10T1/2 fibroblasts.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a class of carcinogenic chemicals
      that are ubiquitous in the environment. Fjord-region naphthopyrene isomers are
      structurally similar to the potent fjord-region PAH carcinogen dibenzo[a,l]pyrene
      and thus have the potential to be potent carcinogens. Naphtho[1,2-a]pyrene (N[1,2
      a]P) exhibited similar bacterial mutagenicity and morphological cell transforming
      activity when compared to benzo[a]pyrene (B[a]P), whereas the structural isomer,
      naphtho[1,2-e]pyrene (N[1,2-e]P) was inactive is these bioassays. In this study,
      we examined the formation of DNA adducts in C3H10T1/2Cl8 (C3H10T1/2) mouse embryo
      fibroblasts exposed to N[1,2-a]P or N[1,2-e]P and their respective dihydrodiols.
      The DNA adducts were characterized by co-chromatography with reaction products
      from anti-N[1,2-a]P diol epoxide (DE) or anti-N[1,2-e]PDE and polydeoxyadenosine
      (dAdo) or oligodeoxyguanosine (dGuo). C3H10T1/2 fibroblasts exposed to N[1,2-a]P
      or N[1,2-a]P-9,10-diol produced both anti-N[1,2-a]P-DE-dAdo and -dGuo adducts
      with total DNA adduction levels of 22.2 to 33.3 pmol DNA adducts/mug DNA.
      C3H10T1/2 fibroblasts exposed to N[1,2-e]P produced 2 major and 1 minor adducts.
      C3H10T1/2 fibroblasts exposed to N[1,2-e]P-11,12-diol produced 2 major adducts.
      All of the identified adducts were anti-N[1,2-e]PDE-dGuo and -dAdo adducts. While
      the total DNA adduct level in N[1,2-e]P-11,12-diol-treated fibroblasts was
      extremely high, 105.9 pmol DNA adducts/mug DNA, the level in N[1,2-e]P-treated
      fibroblasts was 1.47 pmol DNA adducts/microg DNA. We conclude that lack of
      biological activity of N[1,2-e]P may be related to its inability to form
      sufficient amounts of N[1,2-e]P-11,12-diol, which would then be metabolized to
      sufficient amounts of anti-N[1,2-e]PDE needed to transform these fibroblasts.

PMID- 16814462
TI  - Improvement of paint effluents coagulation using natural and synthetic coagulant
      aids.
AB  - The coagulant iron chloride and the flocculants Polysep 3000 (PO), Superfloc A
      1820 (SU) and Praestol 2515 TR (PR) have been used in this study to show the
      efficiency of coagulation flocculation process in the chemical precipitation
      method for the removal of organic and colouring matters from the paint industry
      wastewater. This study also includes the amount of produced sludge. The results
      indicate that FeCl(3) is efficient at pH range 8-9 and at optimal dose of 650
      mgl(-1). Iron chloride allows the removal of 82% of chemical oxygen demand (COD)
      and 94% of colour. However, sequential addition of coagulant and polymeric
      additives enhance clearly pollutant removal and produces less decanted sludge
      compared to the results obtained when the coagulant is used alone. The removal
      efficiency of COD reaches 91% and that of colour 99%. Coagulation-biflocculation
      process is more effective than the coagulation-monoflocculation one. The
      sequential addition of iron chloride, Polysep 3000 (cationic flocculant) and
      Praestol 2515 TR (anionic flocculant) seems to be the most suitable combination
      for the treatment of the paint industry wastewaters.

PMID- 16814463
TI  - Adsorption and recovery of lead(II) from aqueous solutions by immobilized
      Pseudomonas Aeruginosa PU21 beads.
AB  - In this study, immobilized Pseudomonas aeruginosa PU21 beads were used as an
      adsorbent for lead(II). Different weight percentages of chitosan were added to
      polyethylene glycol (PEG, 0.5 wt.% in aqueous solution) and alginate (18 wt.% in
      aqueous solution), and then blended or cross-linked using different
      concentrations of epichlorohydrin (ECH) to prepare beads of different sizes and
      increased mechanical strength. Before blending or cross-linking, different weight
      percentages of P. aeruginosa PU21 were added to increase lead(II) adsorption.
      Subsequently the optimized bead composition (concentration of ECH, percentages of
      chitosan and P. aeruginosa PU21) and the optimum adsorption conditions (agitation
      rate and pH in the aqueous solution) were ascertained. Finally, the optimized
      beads adsorbing lead(II) were regenerated by 0.1M aqueous HCl solutions and the
      most effective desorption agitation rate was ascertained. The results indicate
      that the reuse of immobilized P. aeruginosa PU21 beads was feasible. In addition,
      the equilibrium adsorption, kinetics, changes in the thermodynamic properties of
      adsorption of lead(II) on optimized beads were also investigated.

PMID- 16814464
TI  - Photocatalytic decomposition of 2-chlorophenol in aqueous solution by UV/TiO2
      process with applied external bias voltage.
AB  - The decomposition of 2-chlorophenol by UV/TiO2 process with the application of
      external bias voltage was examined in this study. Experiments were conducted in a
      batch reactor using TiO2-coated titanium sheet as anode and platinum sheet as
      cathode. The anode photocatalysis of 2-chlorophenol was totally inhibited for
      experiments conducted with the application of external anodic bias voltage lower
      than the flat band potential of TiO2. The decomposition rate of 2-chlorophenol
      was then increased with increasing external anodic bias voltage applied up to 0.0
      V (versus SCE). The application of external bias voltage higher than 1.0 V did
      not markedly promote the photocatalysis of 2-chlorophenol possibly because the
      photocurrent induced was constant. Experimental results indicated that the
      decomposition of 2-chlorophenol was more effective for experiments conducted in
      acidic solutions due to the lower flat band potential of TiO2 and the higher
      photocurrent induced. The presence of electron scavengers in aqueous solution,
      such as oxygen molecules, may increase the decomposition rate of 2-chlorophenol.
      However, the effect of dissolved oxygen was diminished for experiments conducted
      with applied external bias voltage. The photocatalytic decomposition rate of 2
      chlorophenol was enhanced linearly with the increasing UV light intensity when
      the external bias voltage was applied.

PMID- 16814465
TI  - Wet oxidation of acid brown dye by hydrogen peroxide using heterogeneous catalyst
      Mn-salen-Y zeolite: a potential catalyst.
AB  - Catalytic wet hydrogen peroxide oxidation of acid dye has been explored in this
      study. Manganese(III) complex of N,N'-ethylene bis(salicylidene-aminato)
      (salenH(2)) has been encapsulated in super cages of zeolite-Y by flexible ligand
      method. The catalyst has been characterized by FT-IR, XRD, TG/DTA and nitrogen
      adsorption studies. The effects of various parameters such as pH, catalyst and
      hydrogen peroxide concentration on the oxidation of dye were studied. The results
      indicate that after 20 min at 30 degrees C, 0.175 M H(2)O(2) and 3g/L catalyst,
      about 90% dye removal was obtained. These studies indicate that manganese-salen
      complex immobilized on zeolite framework can act as a good heterogeneous catalyst
      for removal of dye from wastewaters.

PMID- 16814466
TI  - Optimization of integrated chemical-biological degradation of a reactive azo dye
      using response surface methodology.
AB  - The integrated chemical-biological degradation combining advanced oxidation by
      UV/H(2)O(2) followed by aerobic biodegradation was used to degrade C.I. Reactive
      Azo Red 195A, commonly used in the textile industry in Australia. An experimental
      design based on the response surface method was applied to evaluate the
      interactive effects of influencing factors (UV irradiation time, initial hydrogen
      peroxide dosage and recirculation ratio of the system) on decolourisation
      efficiency and optimizing the operating conditions of the treatment process. The
      effects were determined by the measurement of dye concentration and soluble
      chemical oxygen demand (S-COD). The results showed that the dye and S-COD removal
      were affected by all factors individually and interactively. Maximal colour
      degradation performance was predicted, and experimentally validated, with no
      recirculation, 30 min UV irradiation and 500 mgH(2)O(2)/L. The model predictions
      for colour removal, based on a three-factor/five-level Box-Wilson central
      composite design and the response surface method analysis, were found to be very
      close to additional experimental results obtained under near optimal conditions.
      This demonstrates the benefits of this approach in achieving good predictions
      while minimising the number of experiments required.

PMID- 16814467
TI  - Decomposition of some polynitro arenes initiated by heat and shock Part II:
      Several N-(2,4,6-trinitrophenyl)-substituted amino derivatives.
AB  - Samples of 2,4,6-trinitroaniline (PAM), 2,4,6-trinitro-N-(2,4,6
      trinitrophenyl)aniline (DPA), N,N'-bis(2,4,6-trinitrophenyl)-3,5-dinitropyridine
      2,6-diamine (PYX) and N,N',N''-tris(2,4,6-trinitrophenyl)-1,3,5-triazine-2,4,6
      triamine (TPM) were exposed to heat or to shock and then analysed
      chromatographically (LC-UV and LC/MS). It was found that the main identified
      decomposition products of these two incomplete initiations are identical for each
      of the compounds studied. It has been stated that the chemical micro-mechanism of
      the primary fragmentations of their low-temperature decomposition should be the
      same as in the case of their initiation by shock, including fragmentation during
      their detonation transformation.

PMID- 16814468
TI  - Glutamate stimulation increases hormone release in rat melanotrophs.
AB  - In melanotrophs, neuroendocrine cells from the intermediate lobe of the rat
      pituitary gland, glutamate causes a rise in intracellular [Ca2+] suggesting the
      presence of ionotropic NMDA and non-NMDA AMPA/K receptors. However, the Ca(2+)
      dependent release of the major peptide hormone, alpha-melanocyte stimulating
      hormone (alpha-MSH), in response to glutamate stimulation has not been studied
      yet in this cell model. Significant spontaneous secretion of the peptide, which
      results in hormone deposits on the perimeter of the cells, has been confirmed by
      using confocal microscopy. Co-staining with a membrane area marker FM 1-43, which
      co-localized with the immunocytochemically marked hormone deposits, showed that
      fusion-competent sites on the plasma membrane coincided with secretion-competent
      sites. Stimulation of the cells with glutamate and high K+ saline induced a
      significant increase in the plasma membrane area covered with alpha-MSH deposits
      compared to control cells incubated with glutamate and CNQX, a glutamate channel
      blocker. The optical approach to monitor the secretory activity of a single
      neuroendocrine cell revealed that glutamate stimulates the release of alpha-MSH
      at distinct exocytotic membrane domains only.

PMID- 16814469
TI  - Human platelets express the synaptic markers VGLUT1 and 2 and release glutamate
      following aggregation.
AB  - Vesicular glutamate transporters (VGLUTs) are involved in storing glutamate for
      secretion at the level of glutamatergic axon terminals, and for this reason they
      have been extensively used as markers to identify glutamate-releasing cells.
      Platelets have been considered as a suitable model for studying glutamatergic
      dysfunction because they perform glutamate uptake and express both external
      transporters, and NMDA-like receptors. Here, we show that platelets express the
      pre-synaptic markers VGLUT1 and VGLUT2 and release glutamate following
      aggregation, implying a possible contributory role in the pathophysiology of
      stroke, migraine, and other excitotoxic disorders.

PMID- 16814470
TI  - Temporomandibular joint synovial fibroblasts mediate serine proteinase dependent
      Type I collagen degradation.
AB  - Degenerative temporomandibular joint (TMJ) disorders are characterized by the
      excessive turnover of collagen. In addition to the matrix metalloproteinase (MMP)
      and cathepsin mediated collagen degradation pathways, a serine proteinase
      dependent pathway has recently been identified in TMJ fibroblasts. This study
      focused on further characterizing this serine proteinase pathway utilizing a
      media-mediated collagen degradation assay and zymography. The conditioned media
      from cell-mediated collagen degradation assays were incubated with Type I
      collagen at pH 7.5 with or without a MMP inhibitor (1,10-phenanthroline), serine
      proteinase inhibitors (alpha1-antitrypsin and soybean trypsin inhibitor, STI), or
      cysteine proteinase inhibitors. The data showed that 1,10-phenanthroline and STI
      reduced the collagen cleavage by 12.33% and 47.78%, respectively. The cysteine
      proteinase inhibitors had no effect. The combination of alpha1-antitrypsin and
      1,10-phenanthroline inhibited the cleavage by 79.22%, while STI and 1,10
      phenanthroline together blocked the cleavage by 85.44%. Zymography identified a
      proteinase at approximate 22.5 kDa, which was more effectively blocked by serine
      proteinase inhibitors than by MMP or cysteine proteinase inhibitors. Reverse
      transcript-PCR and real-time PCR results demonstrated that TMJ cells did not
      express trypsinogen-2 mRNA, a collagen cleaving serine proteinase. This study
      demonstrated that TMJ fibroblasts can predominantly utilize a serine proteinase
      to mediate collagen degradation, which is not trypsinogen-2.

PMID- 16814471
TI  - Mechanism of altered TNF-alpha expression by macrophage and the modulatory effect
      of Panax notoginseng saponins in scald mice.
AB  - AIM: To explore the mechanism of altered tumor necrosis factor-alpha (TNF-alpha)
      expression by peritoneal macrophages (PMPhi) and Panax notoginseng saponins (PNS)
      modulation in light of NF-kappaB signal transduction in severely scalded mice.
      METHODS: Eighteen percent total body surface area (TBSA) full-thickness scalded
      mice were used. PMPhi was collected at different time intervals (0, 2, 6, 12, 24
      and 48 post-burn hour (PBH)) separately. The following parameters were measured:
      TNF-alpha mRNA and IL-10 mRNA expression (reverse transcription-polymerase chain
      reaction, RT-PCR), protein kinase C (PKC) activity (isotope incorporation
      analysis), NF-kappaB activity (electrophoretic mobility shift assay, EMSA),
      IkappaB-alpha expression (Western blot). RESULTS: After scald, increased
      expression of TNF-alpha mRNA of PMPhi peaked at 12 PBH. Meanwhile, expression of
      IL-10 mRNA dropped to the lowest level at 12 PBH. NF-kappaB activity was markedly
      activated and reached its peak at 2 PBH. Membrane PKC activity was up-regulated
      after scald and showed a positive correlation with the change of TNF-alpha mRNA.
      Expression of IkappaB-alpha first decreased at 2 PBH and then increased to high
      level at 24 PBH. When 12 PBH was chosen as the time point for in vitro
      intervention with the application of specific NF-kappaB inhibitor pyrrolidine
      dithiocarbamate (PDTC), PKC inhibitor H-7 and PNS, both TNF-alpha mRNA expression
      and NF-kappaB activity decreased significantly. CONCLUSIONS: These results
      indicate that abnormal expression of TNF-alpha mRNA of macrophages might be
      regulated by PKC-NF-kappaB signaling following severe burn. PNS might play an
      anti-inflammatory effect by inhibiting NF-kappaB activity and TNF-alpha mRNA
      expression.

PMID- 16814472
TI  - Use of free dorsoulnar perforator flap in the treatment of postburn contractures
      of the fingers.
AB  - BACKGROUND: Burns of the hand cause not only the impairment of hand function but
      also cosmetic deformity. Cases with dysfunctional hands with severe contractures
      increase if rehabilitation of the acutely burned hand is not done properly.
      PURPOSE: We present the use of free dorsoulnar perforator flap in the treatment
      of postburn contractures as an alternative when local flaps cannot be used.
      METHODS: Free dorsoulnar perforator flap was used in the treatment of seven hands
      with postburn contracture. Five of them had multiple digital postburn flexion
      contractures. Combined use of cross-finger and side finger transposition flaps
      was preferred when the adjacent finger was suitable for being cross-finger flap
      donor. When the adjacent finger was not suitable for being cross-finger flap
      donor, the free dorsoulnar perforator flap was preferred. Two of the patients had
      postburn web contractures. Free dorsoulnar perforator flap was used to release
      the web and to form a new web commissure. CONCLUSION: The free dorsoulnar
      perforator flap could be a good alternative to cover the defects created with the
      hand contracture release.

PMID- 16814473
TI  - Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in
      humans.
AB  - Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS)
      receptor. It is hypothesised to play a key role in energy balance stimulating
      food intake and body weight. Besides GH-releasing hormone (GHRH) and
      somatostatin, it is thought to be a regulating factor of GH release. Ghrelin also
      appears to be involved in sleep regulation. We showed recently that ghrelin
      promotes slow-wave sleep and the nocturnal release of GH, cortisol and prolactin
      in humans. Similarly, promotion of non-rapid-eye-movement (NREM) sleep was
      reported in mice after systemic ghrelin. If ghrelin is a factor that induces
      and/or maintains sleep, it should be enhanced after a period of sleep deprivation
      (SD). To clarify this issue, nocturnal ghrelin, GH, ACTH and cortisol plasma
      concentrations were determined and simultaneously sleep electroencephalogram
      (EEG) was recorded (2300-0700 h) during sleep before and after 1 night of total
      SD in 8 healthy subjects. Compared to baseline, ghrelin levels increased earlier
      by a non-significant trend, already before the beginning of recovery sleep.
      Further a non-significant trend occurred, suggesting higher ghrelin secretion in
      the first half of the night. The ghrelin maximum was found significantly earlier
      after SD than at baseline. GH secretion during the first half of the night and
      total night after SD were elevated. ACTH and cortisol were also elevated, which
      was most pronounced during the second half of the night. No effects of SD on the
      time of the maximum were found for GH, ACTH and cortisol. The increase in ACTH
      after SD is a novel finding. Whereas the effects of SD on ghrelin levels were
      relatively weak, our findings are in line with the hypothesis that ghrelin is a
      sleep-promoting factor in humans. Ghrelin may be involved in sleep promotion
      after SD.

PMID- 16814474
TI  - Divalproex utility in bipolar disorder with co-occurring cocaine dependence: a
      pilot study.
AB  - OBJECTIVE: The aim of this open-label pilot study was to evaluate the utility of
      divalproex in decreasing cocaine use and stabilizing mood symptoms among patients
      with bipolar disorder with comorbid cocaine dependence. METHOD: Fifteen patients
      enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID
      diagnoses of bipolar I disorder and comorbid cocaine dependence with active
      cocaine use. Patients were started on open-label divalproex. After stabilization
      on divalproex sodium, weekly assessments were undertaken for 8weeks. Subjects
      also attended dual recovery counseling. RESULTS: The results revealed significant
      improvement on % cocaine abstinent days, dollars spent on cocaine, ASI's drug use
      severity index, % alcohol abstinent days, drinks per drinking day, marijuana use
      and cigarettes smoking. They also had significant improvement on manic,
      depressive, and sleep symptoms and on functioning. There were no reported adverse
      events or increases in liver function tests. CONCLUSION: The results of this open
      label study point to the potential utility of divalproex in patients with bipolar
      disorder and primary cocaine dependence. Double-blind, placebo-controlled studies
      to fully evaluate the efficacy of divalproex in this high risk clinical
      population are warranted.

PMID- 16814475
TI  - Demographic differences in support for smoking policy interventions.
AB  - The Smoking Policy Inventory (SPI) is a 35-item scale, which measures attitudes
      towards tobacco control policies. The five dimensions of the SPI are advertising
      and promotion, public education, laws and penalties, taxes and fees, and
      restrictions on smoking. The SPI has been applied to different samples, both in
      the USA and internationally. However, no one has investigated if there is
      differential support for policy intervention among subgroups within the USA. This
      study investigated subgroup differences on five demographic variables (gender,
      age, race, ethnicity, and education) across the five dimensions of the SPI. A
      random digit dial sample of 506 adult participants from the United States was
      analyzed with five MANOVAs and follow-up ANOVAs. Men (N=188) had significantly
      (p<0.05) less favorable attitudes towards tobacco control policies than women
      (N=317) on all five scales. Blacks (N=52) had significantly (p<0.05) more
      favorable attitudes than whites (N=410) on increasing public education. There
      were no significant differences between Hispanics (N=21) and non-Hispanics
      (N=469). Older people were significantly (p<0.05) more supportive of restrictions
      on advertising and promotion, increasing public education, and increasing
      environmental restrictions. More educated people were significantly (p<0.05) more
      supportive of increasing taxes and fees and increasing environmental
      restrictions. These subgroup differences could be employed to guide the targeting
      of changes in policies and interventions to the specific concerns of the various
      groups.

PMID- 16814476
TI  - Vasopressin and oxytocin as neurohormonal mediators of MDMA (ecstasy) sociosexual
      behavioural effects.

PMID- 16814477
TI  - Is Lyme disease always poly microbial?--The jigsaw hypothesis.
AB  - Lyme disease is considered to be caused by Borrelia species of bacteria but
      slowly evidence is accumulating which suggests that Lyme disease is a far more
      complex condition than Borreliosis alone. This hypothesis suggests that it may be
      more appropriate to regard Lyme disease as a tick borne disease complex. Over
      recent years numerous different microbes have been found in ticks which are known
      to be zoonotic and can coinfect the human host. The hypothesis suggests that
      multiple coinfections are invariably present in the clinical syndromes associated
      with Lyme disease and it is suggested that these act synergistically in complex
      ways. It may be that patterns of coinfection and host factors are the main
      determinants of the variable clinical features of Lyme disease rather than
      Borrelia types. An analogy with a jigsaw puzzle is presented with pieces
      representing Borreliae, coinfections and host factors. It is suggested that many
      pieces of the puzzle are missing and our knowledge of how the pieces fit together
      is rudimentary. It is hoped that the hypothesis will help our understanding of
      this complex, enigmatic condition.

PMID- 16814478
TI  - Can heart rate variability timing reflect the body stress?

PMID- 16814479
TI  - Serum acetylcholinesterase activity as a putative link between anxiety symptoms
      and atherosclerosis risk.

PMID- 16814480
TI  - It is likely that the risk of cardiovascular events from pharmaceuticals as COX-2
      inhibitors can be reduced significantly by standard pharmaceutical and lifestyle
      preventative measures.
AB  - Based on the principles of the altered homeostatic theory, a case will be made
      that the risk of cardiovascular (CV) events from pharmaceuticals as COX-2
      inhibitors (coxibs) and sympatho-mimetic drugs can be reduced significantly by
      using standard pharmaceutical and lifestyle preventative measures as statins,
      exercise, a proper diet, and weight and stress reduction. The standard method of
      preventing CV events from coxibs, the prototypical pharmaceuticals which induce
      CV events, is not overly helpful; this method is based essentially on limitation
      of coxibs to low risk individuals, and to low dose and short term usage. Use of
      standard preventative measures apparently had not been considered because coxib
      induced CV events are regarded as "special" as they are attributed to
      thromboxane. "Regular" CV events are attributed basically to dyslipidemia, and
      standard preventative measures are designed to improve dyslipidemia; therefore,
      it probably has been assumed that standard therapy for "regular" CV events would
      not be applicable to coxib-induced infarctions. In contrast, the altered
      homeostatic theory treats pharmaceuticals which induce CV events as "regular"
      risk factors which induce "regular" CV events. Therefore, "regular" preventative
      measures as exercise and statins should reduce the incidence of pharmaceutical
      induced CV events. The critical issue is the mechanism of CV events. Thrombosis
      is the accepted and vasoconstriction (spasm of resistance vessels) is a proposed
      mechanism for CV events, and thrombosis and/or vasoconstriction
      (thrombosis/vasoconstriction) is regarded as the direct mechanism of CV events.
      Multiple and diverse "regular" risk factors express thrombosis/vasoconstriction,
      and multiple and diverse pharmaceutical and lifestyle preventative measures
      express anti-thrombosis/vasodilation. Risk and preventative factors are
      considered to operate in a dynamic balance; dominance of
      thrombosis/vasoconstriction favors development of CV events, and dominance of
      anti-thrombosis/vasodilation favors prevention of CV events. Thromboxane, and
      thus coxibs, and sympatho-mimetic drugs also express thrombosis/vasoconstriction;
      it is this expression which makes pharmaceuticals "regular" risk factors which
      induce "regular" CV events. It is assumed that all pharmaceuticals which induce
      CV events express thrombosis/vasoconstriction; thrombosis/vasoconstriction is the
      obvious mechanism for CV events from any source, and expression of
      thrombosis/vasoconstriction by multiple and diverse "regular" risk factors is
      supportive. Just as standard pharmaceutical and lifestyle preventative agent
      significantly reduce the risk of "regular" CV events, such measures should
      significantly reduce the risk of pharmaceuticals which favor CV events;
      protection is effected by shifting the overall balance between
      thrombosis/vasoconstriction and anti-thrombosis/vasodilation beneficially towards
      dominance of anti-thrombosis/vasodilation.

PMID- 16814481
TI  - Low bone mineral density value at the time of diagnosis of primary tumor in
      postmenopausal patients with operable breast cancer may increase bone metastasis
      risk.

PMID- 16814482
TI  - Are prions related to the emergence of early life?
AB  - DNA and RNA are the modern cellular molecules related to the storage and
      processing of the genetic information. However, in the Earth primeval environment
      conditions, these two molecules are far from being the best option for this
      function due to their great complexity and sensibility to heat. Experiments have
      been showing that proteins are very stable and reliable molecules even in very
      extreme conditions and, under certain circumstances, could be related to the
      transmission of certain phenotypes that are inherited in a non-Mendelian manner.
      Prions, infective proteins that are associated to several neurological diseases
      among mammals by replacing their dominant native state of prion protein by a
      misfolded one, are remarkably resistant to even the most extreme environments.
      Furthermore, prions are also associated to the transmission of certain fungal
      traits in an epigenetical model. These two characteristics support the hypothesis
      that prions are a possible relic of early stage peptide evolution and may
      represent the reminiscence of a very ancient analogical code of biological
      transmission of information rather than the digital one represented by modern
      nucleic acids.

PMID- 16814483
TI  - Rebound of inflammatory response after withdrawal of statins does not increases
      event rates in patients with stable cardiac disease.

PMID- 16814484
TI  - Altered expression of the KLF4 in colorectal cancers.
AB  - KLF4 is an important regulator of cell proliferation and is maximally expressed
      in epithelial cells of the gastrointestinal tract. Inactivation of the KLF4 gene
      by genetic and epigenetic alterations has been reported in colorectal cancers,
      but the expression pattern of the KLF4 protein has not been studied. Here, to
      investigate the roles of KLF4 in colorectal carcinogenesis, we examined the
      expression pattern of the KLF4 protein in 123 colorectal cancers by
      immunohistochemistry using tissue microarray. Moderate to strong nuclear staining
      for KLF4 was found in normal colonic mucosa. Interestingly, loss of KLF4
      expression was observed in 30 (24.4%) of 123 colorectal cancers. Statistically,
      loss of KLF4 protein expression was not associated with clinocopathologic
      parameters, including tumor stage (Bartholomew test, P>0.05), lymph node
      metastasis, differentiation, tumor location, and tumor size (chi2 test, P>0.05).
      These results indicate that loss of the KLF4 expression might play a role in
      tumor development as an early event for a subset of colorectal cancers.

PMID- 16814485
TI  - Two new benzylbenzoate glucosides from Curculigo orchioides.
AB  - An extract from in vitro cultures of Curculigo orchioides grown as bulbils in
      shake flasks, afforded two new glucosides of substituted benzylbenzoate -
      curculigoside C (3) and curculigoside D (4) - together with two known compounds -
      curculigoside A (1) and curculigoside B (2). Their structures were elucidated on
      the basis of spectral evidence, in particular by using 2D NMR methods. Their
      vasoactive properties were assessed in isolated rat aortic rings.

PMID- 16814486
TI  - Evaluation of the antitussive effect of stigma and petals of saffron (Crocus
      sativus) and its components, safranal and crocin in guinea pigs.
AB  - The antitussive activity of Crocus sativus stigma and petal extracts and its
      components, safranal and crocin, was evaluated using the nebolized solution of
      citric acid 20% in guinea pigs. The extract and agents were injected
      intraperitoneally. The ethanolic extract of C. sativus (100-800 mg/kg) and
      safranal (0.25-0.75 ml/kg) reduced the number of cough. The ethanolic and aqueous
      extracts of petal and crocin did not show antitussive activity.

PMID- 16814487
TI  - Anti-ulcerogenic activity of the aerial parts of Lithraea molleoides.
AB  - The hydro-alcoholic extract of the aerial parts of Lithraea molleoides, given
      orally at a dose of 1000 mg/kg, showed significant anti-ulcerogenic activity on
      ulcer induced by indomethacin and absolute alcohol in rats.

PMID- 16814488
TI  - A note on the effect of the full moon on the activity of wild maned wolves,
      Chrysocyon brachyurus.
AB  - It is well established in the scientific literature that animal prey species
      reduce their activity at times of high predation risk. In the case of nocturnal
      animals this occurs when there is a full moon; however, the response of predators
      to the changes in their prey behaviour is relatively unknown. Two responses are
      possible: (1) increase in search effort to maintain food intake; or (2) decrease
      in distance travelled due to either: (a) an effort to conserve energy or (b)
      increased kill efficiency. Using GPS tracking collars we monitored the distances
      travelled (which is representative of search effort) by three maned wolves during
      the night of the full and new moon for five lunar cycles (during the dry season).
      A Wilcoxon matched-paired test showed that the maned wolves travelled
      significantly less during the full compared to the new moon (p < 0.05). On
      average, during the 10 h of darkness during a full moon maned wolves travelled
      1.88 km less than on a new moon. These data suggest that maned wolves respond to
      temporally reduced prey availability by reducing their distance travelled.

PMID- 16814489
TI  - DSM-IV alcohol dependence and abuse: further evidence of validity in the general
      population.
AB  - BACKGROUND: In order to understand the validity of the Diagnostic and Statistical
      Manual of Mental Disorders, 4th ed. (DSM-IV) alcohol abuse and dependence
      diagnoses, studies are needed in both clinical and general population samples.
      The purpose of this study was to examine the construct and criterion-oriented
      validity of DSM-IV alcohol dependence and abuse in the general population with
      respect to factor structure and their relationship to family history of
      alcoholism, treatment utilization, and psychiatric comorbidity. METHODS: This
      analysis is based on data from the 2001-2002 National Epidemiologic Survey on
      Alcohol and Related Conditions (NESARC), in which nationally representative data
      were collected in personal interviews conducted with one randomly selected adult
      in each sample household or group quarters. A subset (n=26,946) of the NESARC
      sample (total n=43,093) who reported drinking one or more drinks during the year
      preceding the interview formed the basis of analyses. Latent variable modeling
      was used to assess the concurrent validity of DSM-IV alcohol abuse and dependence
      symptom items. RESULTS: The latent variable modeling yielded one major factor
      related to alcohol dependence, a second factor related to alcohol abuse and a
      third smaller factor defined by tolerance. The validity of alcohol dependence in
      general population samples was further supported by statistically significant
      associations with family history of alcoholism, treatment utilization, and
      psychiatric and medical comorbidities. CONCLUSIONS: The factor structure and
      relationship to external criterion variables observed in the study provide
      support for the further validity of DSM-IV alcohol dependence in the general
      population, whereas support for the validity of DSM-IV abuse was equivocal.

PMID- 16814490
TI  - Stimulant use and symptoms of abuse/dependence: epidemiology and associations
      with cannabis use--a twin study.
AB  - BACKGROUND: This paper explores the magnitude of--and extent of overlap between-
      additive genetic, shared environmental and non-shared environmental influences on
      lifetime stimulant use and on stimulant abuse/dependence symptoms; the
      associations between stimulant use and cannabis use and the extent to which these
      associations can be attributed to common or correlated genetic and environmental
      influences. METHODS: Self-report data on lifetime stimulant use, abuse/dependence
      symptoms and corresponding measures of cannabis involvement were collected from a
      sample of 6265 male and female Australian twins born 1964-1971. RESULTS:
      Approximately one in five study participants reported lifetime stimulant use
      while 5% reported experiencing at least one symptom of abuse/dependence.
      Multivariate genetic model fitting indicated moderate genetic influences on
      stimulant use (40%) and symptoms (65%) while there was no evidence of sex
      differences in the magnitude of these influences. Despite some overlap in genetic
      influences on these measures, approximately 60% of the genetic variance in
      symptoms was specific to this phenotype. There were also strong genetic and
      shared environmental correlations between the factors associated with stimulant
      use and those associated with cannabis use. CONCLUSIONS: There were moderate
      genetic influences on stimulant use and stimulant abuse/dependence with moderate
      overlap between the genetic factors associated with these outcomes. Additionally,
      there were strong associations between measures of lifetime stimulant use and
      analogous measures of cannabis use which, importantly, could be largely
      attributed to shared familial risk factors predisposing to both stimulant and
      cannabis use.

PMID- 16814491
TI  - Highly efficient generation of signal transduction knockout mutants using a
      fungal strain deficient in the mammalian ku70 ortholog.
AB  - Targeted gene replacement via homologous recombination is a routinely used
      approach to elucidate the function of unknown genes. Integration of exogenous DNA
      in the genomic DNA requires the action of double-strand repair mechanisms. The
      filamentous ascomycete Sordaria macrospora is a model system for studying
      fruiting body development in fungi. In contrast to the budding yeast
      Saccharomyces cerevisiae, but similar to many filamentous fungi, plants and
      animals, transformed DNA is ectopically integrated into the genome of S.
      macrospora. Most probably this occurs by non-homologous end joining (NHEJ), a
      mechanism that involves the binding of the Ku heterodimer (Ku70/Ku80) at the ends
      of a DNA double-strand break (DSB). Phylogenetic analysis of Ku70 orthologs of
      fungal, plant, and animal origin reveals that the Ku70 protein is well conserved
      among eukaryotes. To improve gene targeting efficiency in S. macrospora, we
      identified and deleted the S. macrospora ku70 gene. No impairment of the
      Deltaku70 mutant in vegetative or fruiting body nor ascospore development was
      observed making this strain an ideal recipient for gene targeting of
      developmental genes. As a case study, the S. macrospora Deltaku70 strain was used
      for targeted deletion of the pheromone gene ppg2 and the pheromone receptor gene
      pre2. PCR generated deletion constructs containing 1000 bp of homologous flanking
      sequence resulted in a drastically increased gene targeting efficiency. As a
      consequence, almost all transformants generated carried a disrupted target gene.

PMID- 16814492
TI  - Expression and tissue distribution of mouse Hax1.
AB  - HAX1 is an ubiquitously expressed human gene. Though a number of cellular and
      viral proteins are known to interact with HAX1, its function is still not
      completely understood. On the basis of these identified interaction partners,
      HAX1 seems to play a role in apoptosis and the organization of the cytoskeleton.
      The cDNAs for human and mouse Hax1 share 86% identity and 80% identity at the
      protein level, suggesting a similar functional importance. To date, no conclusive
      data on the tissue specific expression of the murine Hax1 are available and only
      one interaction partner has been identified. Here, we show a detailed expression
      analysis for the murine ortholog by RT-PCR, Northern and Western blot.
      Furthermore, the distribution of Hax1 within different mouse tissues was studied
      by immunohistochemistry (IHC). In general, we found a good correlation between
      the results obtained from different detection techniques. Similar to its human
      counterpart, mouse Hax1 seems to be ubiquitously expressed. At the RNA level, we
      found the highest expression of Hax1 in liver, kidney and testis. In sharp
      contrast to the human HAX1 which is highly expressed in skeletal muscle, the
      mouse ortholog was detected only at very low levels. Using a specific antibody,
      we detected Hax1 in the majority of mouse tissues by IHC. Interestingly, the most
      prominent expression of Hax1 was found in epithelial, endothelial and muscle
      cells. Surprisingly, thymus, spleen and pancreas did not show detectable
      immunostaining. Furthermore, we have studied the subcellular localisation of Hax1
      in a keratinocyte and a neuronal cell line by immunofluorescence. We found Hax1
      to be localised mainly in the cytoplasm and detected a partial colocalisation
      with mitochondria. The results presented here summarize for the first time the
      expression of the murine Hax1 in different tissues and two cell lines. Further
      studies will elucidate the functional importance of this protein in individual
      cell types with respect to structural aspects, cell mobility and apoptosis.

PMID- 16814493
TI  - Maternal smoking during pregnancy and possible effects of in utero testosterone:
      evidence from the 2D:4D finger length ratio.
AB  - OBJECTIVES: Maternal smoking during pregnancy is linked to high fetal
      testosterone (FT), and an increased risk in offspring for autism, ADHD, conduct
      disorder, antisocial behaviour and criminal outcomes. The ratio of the length of
      the 2nd and 4th fingers (2D:4D) is thought to be negatively related to FT
      concentration, and is related to autism, hyperactivity, poor social behaviour,
      and physical aggression. We compare the 2D:4D ratio of children whose mothers
      smoked during pregnancy with the 2D:4D of children whose mother did not smoke.
      METHOD: Cross-sectional survey in two primary schools. Questionnaires were
      distributed to 710 children and 546 were returned. Of these the 2nd and 4th
      digits of 520 children (259 females and 261 males) were measured. The main
      outcome measures were 2nd and 4th digit length, smoking history of mother and
      father. RESULTS: Boys had lower mean 2D:4D than girls and right 2D:4D was lower
      than left. Among boys, those whose mother's smoked during pregnancy had lower
      right hand 2D:4D ratio than those whose mother did not smoke. The difference
      remained significant after the effects of age, height, weight and birth weight
      were removed. Other household smoking patterns were not associated with male
      offspring 2D:4D. Female offspring 2D:4D did not differ on the basis of maternal
      smoking. CONCLUSIONS: Maternal smoking during pregnancy was associated with low
      right 2D:4D in children, but the effect was restricted to boys. A link between
      maternal smoking during pregnancy and 2D:4D supports a causal association between
      FT and such behaviours as hyperactivity and conduct disorder.

PMID- 16814494
TI  - Effects of the Fusarium toxin deoxynivalenol on tissue protein synthesis in pigs.
AB  - The Fusarium toxin deoxynivalenol is known to be a potent protein synthesis
      inhibitor according to research in different in vitro and in vivo systems.
      However, the significance of this toxic feature was not yet evaluated for the
      pig. Therefore, an experiment was carried out to measure porcine tissue protein
      synthesis employing the so-called flooding dose technique using [(2)H(5)]
      phenylalanine as tracer. A total of 25 male castrated pigs (initial weight of
      23kg) were used. Seventeen pigs were fed the control diet (control) and eight the
      Fusarium toxin-contaminated diet (chronic oral deoxynivalenol (DON)) for
      approximately 4wks. Pigs recruited from the control group were treated with acute
      oral (n=7) and intravenous (i.v.) DON (n=5), and were exposed to the toxin once
      on the day of protein synthesis measurement. The DON-dose given prior to the
      beginning of protein synthesis measurement amounted to 2, 77, 83 and 53microg
      DONkg(-1) live weight for the control group, chronic oral DON-group, acute oral
      DON-group and acute i.v. DON-group, respectively. Protein synthesis expressed as
      fractional synthesis rate (FSR) was significantly reduced in kidneys, spleen and
      ileum of DON-exposed pigs with effects being less pronounced in the acute oral
      DON-group. FSR of liver, skeletal and heart muscle, mesenteric lymph nodes,
      duodenum, jejunum, jejunal mucosa cells, pancreas and lung were not affected by
      DON.

PMID- 16814495
TI  - Inhibition of delayed rectifier K+ currents by copper in acutely dissociated rat
      hippocampal CA1 neurons.
AB  - A growing number of research results demonstrate that copper is an important
      trace element to life. In this study, whole-cell recording made from acutely
      dissociated rat hippocampal CA1 neurons was employed to investigate the actions
      of copper (Cu(2+)) on the delayed rectifier K(+) currents (I(K)). External
      application of various concentrations of Cu(2+) (1-1000microM) reduced the
      amplitude of I(K) in a dose-dependent manner with an IC(50) value of 100microM
      and a Hill coefficient of 0.4. 300microM of Cu(2+) depolarized the I(K)
      activation curves by 12.5mV and hyperpolarized the I(K) state-inactivation curves
      by 17.4mV, respectively. At this concentration, Cu(2+) also significantly
      increased the value of the fast decay time constant (tau(1)), but had no effect
      on the I(K) recovery from inactivation. These results suggest that relevant
      concentrations of copper at physiological and pathological level can influence
      the neuronal excitability of rat hippocampal CA1 neurons by voltage-gated delayed
      rectifier K(+) channels, and such actions are likely involved in the
      pathophysiology of Cu-related Wilson's disease.

PMID- 16814496
TI  - High sensitivity differential scanning calorimetry investigation of the
      interaction between liposomes, lactate dehydrogenase and tyrosinase.
AB  - High sensitivity differential scanning calorimetry (HSDSC) has been used to study
      the interaction of the model proteins lactate dehydrogenase (LDH) and tyrosinase
      with dimyristoylphosphatidylcholine (DMPC) liposomes, and relate this to the
      thermal and physical stability of the proteins. On heating, both LDH and
      tyrosinase denatured irreversibly in a time-dependent manner and modified the
      phase transition behaviour of DMPC liposomes at all concentrations investigated.
      The most marked effects occurred for the pretransition rather than the main
      phospholipid phase transition. The effects on the bilayer are likely to result
      from electrostatic interactions of the hydrophilic proteins with the head-groups
      of DMPC molecules, whilst due to their hydrophilic nature they do not penetrate
      into the bilayer. Tyrosinase is more highly ionised than LDH at the pH of the
      investigation, which may explain why tyrosinase has a greater effect than LDH on
      the HSDSC scans at mg/ml protein concentrations.

PMID- 16814497
TI  - Straightforward production of encoded microbeads by Flow Focusing: potential
      applications for biomolecule detection.
AB  - Fluorescently encoded polymeric microparticles are acquiring great importance in
      the development of simultaneous multianalyte screening assays. We have developed
      a very versatile and straightforward method for the production of dye-labeled
      microparticles with a very reproducible size distribution and freely-chosen and
      discernible fluorescent properties. Our method combines Flow Focusing technology
      with a solvent evaporation/extraction procedure in a single step, yielding
      spherical, non-aggregate and non-porous particles. We have designed a multi
      coloured bead array which includes the possibility of modifying the surface
      properties of the microparticles, which offer excellent properties for covalent
      attachment of biomolecules such as peptides, oligonucleotides, proteins, etc. We
      also show the potential of the fluorescently labeled microspheres for the
      detection of biomolecule (peptides and oligonucelotides) interactions using flow
      cytometry.

PMID- 16814498
TI  - Prostaglandin inhibitory and antioxidant components of Cistus laurifolius, a
      Turkish medicinal plant.
AB  - As Cistus laurifolius has been used traditionally to treat inflammatory and
      rheumatic disorders, its leaves were tested for prostaglandin (PG) inhibitory and
      antioxidant activities. The leaf extract showed both activities, i.e., inhibitory
      effect at 300 microg/ml on PGE1- and E2-induced contractions in guinea pig ileum
      and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The
      separation guided by the activities shown by these dual assays provided sixteen
      compounds, 1-16. Known compounds 1-12 and 15 were identified as 3-O-methyl
      quercetin (1), 3,7-O-dimethyl quercetin (2), genkwanin (3), 3,7-O-dimethyl
      kaempferol (4), 3,4'-O-dimethyl quercetin (5), apigenin (6), 3,4'-O-dimethyl
      kaempferol (7), ellagic acid (8), beta-sitosterol-3-O-beta-glucoside (9),
      quercetin 3-O-alpha-rhamnoside (10), 5-O-p-coumaroyl quinic acid methyl ester
      (11), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-alpha-l-rhamnopyranoxypropyl)-2
      methoxyphenoxy]-1,3-propanediol (12) and 2,3-dihydro-2-(4'-alpha-l
      rhamnopyranosyloxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-5
      benzofuranpropanol (15). New lignan glycosides 13 and 14 were determined to be
      olivil 9-O-beta-D-xyloside and berchemol 9-O-rhamnoside, respectively. Compound
      16 was isolated as a 2:1 mixture of two diastereomers, the major one of which was
      determined to be (7S,8R)-dihydrodehydrodiconiferyl alcohol 9'-O-alpha-L
      rhamnoside. The structures were determined by detailed 2D NMR analysis together
      with NOEDF and CD. PG inhibitory effect was observed in 1, 5, 10, 12 and 16 at 30
      microg/ml and antioxidant activity, in 1, 2, 8, 10, 12-14 and 16.

PMID- 16814499
TI  - Effect of total phenolics from Laggera alata on acute and chronic inflammation
      models.
AB  - The anti-inflammatory effect of total phenolics from Laggera alata (TPLA) was
      evaluated with various in vivo models of both acute and chronic inflammations. In
      the acute inflammation tests, TPLA inhibited significantly xylene-induced mouse
      ear oedema, carrageenan-induced rat paw oedema and acetic acid-induced mouse
      vascular permeability. In the carrageenan-induced rat pleurisy model, TPLA
      significantly suppressed inflammatory exudate and leukocyte migration, reduced
      the serum levels of lysozyme (LZM) and malondialdehyde (MDA), increased the serum
      levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and
      also decreased the contents of total protein, nitric oxide (NO) and prostaglandin
      E(2) (PGE(2)) in the pleural exudates. In the chronic inflammation experiment,
      TPLA inhibited significantly cotton pellet-induced rat granuloma. These results
      indicated that TPLA possesses potent anti-inflammatory activity on acute and
      chronic inflammation models. Its anti-inflammatory mechanisms are probably
      associated with the inhibition of prostaglandin formation, the influence on the
      antioxidant systems, and the suppression of LZM release. Furthermore, the total
      phenolic content of Laggera alata and its main component type was quantified, and
      its principle components were isolated and authenticated. Acute toxicity studies
      revealed that TPLA up to an oral dose of 8.5 g/kg body weight was almost nontoxic
      in mice.

PMID- 16814500
TI  - In vitro anti-proliferative and antioxidant studies on Devil's Club Oplopanax
      horridus.
AB  - Devil's Club, Oplopanax horridus (OH), is a widely used folk medicine in Alaska
      and British Columbia for treating a variety of ailments including arthritis,
      fever and diabetes. HPLC profiling shows that numerous compounds are present in
      the 70% ethanolic extract of OH dry root bark powder. OH extract inhibited K562,
      HL60, MCF7 and MDA-MB-468 cell growth with the 50% inhibition (IC(50)) estimated
      at 1/2700, 1/1700, 1/500 and 1/2500 dilutions, respectively. Non-cytotoxic
      concentrations (<IC(50)) of OH extract combined with non-cytotoxic concentrations
      (<IC(50)) of camptothecin (CAM) or paclitaxel (PTX) were tested on the tumor cell
      lines. Of the 19 combinations tested, 9 showed additive or synergistic anti
      proliferative effect while the rest showed antagonistic effect. Combination of OH
      extract at 1/4000 and 1/16,000 dilutions with 0.1 microM of CAM produced
      additive, anti-proliferative effects on K562 cells, as did 1/2000 and 1/1000
      dilutions of OH combined with 2.5 nM of PTX on MCF7, and 1/4000 dilution of OH
      with 1 nM of PTX on MDA-MB-468 cells. Combination of 1/8000 and 1/4000 dilution
      of OH with 0.05 microM of CAM showed strong synergistic anti-proliferative
      effects on HL60 cells. At non-cytotoxic 1/4000 dilution, OH induced 13.1% of HL60
      cells to differentiate into granulocytes but had no effect on monocyte/macrophage
      differentiation. A cell free hydroxyl radical scavenging assay estimated that OH
      at 1/100, 1/10 and 1/5 dilutions showed activities equivalent to 2.7, 15.7 and
      25.6 microM of Trolox, respectively. At non-cytotoxic 1/4000 and 1/2000
      dilutions, OH significantly reduced nitric oxide production by lipopolysaccharide
      activated RAW 264.7 cells (p<0.001). Our data show that the ethanolic extract of
      OH has anti-proliferative on several cancer cell lines, and has strong
      antioxidant activity.

PMID- 16814501
TI  - Isolation and structure determination of anti-influenza component from Mahonia
      bealei.
AB  - The fraction possessing anti-influenza activity, which is obtained from the roots
      of Mahonia bealei (Fort), has been studied regarding its chemical compositions
      and molecular structure. The previous experiment on this fraction in vitro
      suggested that the anti-influenza effect was due to the existence of alkaloids in
      M. bealei (Fort), and mainly from one bisbenzylisoquinoline alkaloid. In this
      paper the structure of this bisbenzylisoquinoline alkaloid has been determined as
      1R, 1'S-(+)-isotetrandrine by means of MS, 1H NMR, 13C NMR, FT-IR and HPLC
      analyses.

PMID- 16814502
TI  - Pharmacokinetic features in forensic medicine.
AB  - As a rule, the concentration curves of substances in various body volumes, in
      particular in plasma and blood volume, can be reproduced by a number of
      exponentional functions. A compartment system can be isomorphically assigned to
      such a representation in which a mass exchange takes place between the
      constituent volumes. In forensic medicine (toxicology), the "central compartment
      model" is used in which an exchange of substances between the blood space
      (central compartment) and the peripheral spaces (peripheral compartments) takes
      place. Characteristic parameters of the compartment models are their volumes and
      the intercompartmental mass flows or their rate constants. They can be determined
      from the mathematical representations of the concentration curves. It is possible
      to obtain knowledge on the properties (e.g. permeability) of the
      convectional/diffusional transcapillary transport on the basis of these
      parameters.

PMID- 16814503
TI  - A new sensitive short pentaplex (ShoP) PCR for typing of degraded DNA.
AB  - Analysis of short tandem repeat makers has become the most powerful tool for DNA
      typing in forensic casework analysis. Unfortunately, typing of DNA extracted from
      telogen shed hairs, bones buried in the soil or from paraffin-embedded, formalin
      fixed tissue often reveals no results due to the degradation of DNA. The
      reduction in size of the target fragments by development of new primers and their
      combination in multiplex approaches open a new field of DNA analysis. Here we
      present a new sensitive short pentaplex PCR including the loci amelogenin, TH01,
      VWA, D3S1358 and D8S1179. Validation tests of our new method included
      sensitivity, mixtures, human specificity, artificial degradation of DNA by DNase
      I and case work analysis on a panel of different forensic samples. The detection
      limit was 12.5 pg of human DNA, and mixtures of 50 pg in a total of 1000 pg were
      clearly detectable and revealed complete profiles. Only DNA extracts of human
      primates displayed a few signals, whereas other animal, fungal or bacterial DNA
      showed no signals. Our method proved extremely valuable in the analysis of
      artificially degraded DNA and in forensic cases, where only poorly preserved DNA
      was available. This approach and other similar methods can aid in the analysis of
      samples where allelic drop out of larger fragments is observed. It is highly
      recommended to develop more of these multiplexes to improve poor quality DNA
      typing.

PMID- 16814504
TI  - Phylogeographic investigations: the role of trees in forensic genetics.
AB  - The human mitochondrial DNA (mtDNA) genome is commonly analyzed in various
      disciplines, such as population, medical, and forensic genetics, but conceptual
      and scientific exchange between them is still limited. Here we review several
      aspects of the mtDNA phylogeny that are particularly--but not exclusively--of
      interest to the forensic community. Among the issues that arise, we emphasize the
      importance of integrating evolutionary concepts into the forensic routine. We
      also discuss topics such as mtDNA mutation-rate heterogeneity and the weight of
      evidence, ethnic affiliations of mtDNA profiles, and the abuse of reference
      databases. Finally, we show the usefulness of coding-region variation in a
      forensic context.

PMID- 16814505
TI  - Post-mortem tissue sampling using computed tomography guidance.
AB  - PURPOSE: Currently, in forensic medicine cross-sectional imaging gains
      recognition and a wide use as a non-invasive examination approach. Today,
      computed tomography (CT) or magnetic resonance imaging that are available for
      patients are unable to provide tissue information on the cellular level in a non
      invasive manner and also diatom detection, DNA, bacteriological, chemical
      toxicological and other specific tissue analyses are impossible using radiology.
      We hypothesised that post-mortem minimally invasive tissue sampling using needle
      biopsies under CT guidance might significantly enhance the potential of virtual
      autopsy. The purpose of this study was to test the use of a clinically approved
      biopsy needle for minimally invasive post-mortem sampling of tissue specimens
      under CT guidance. MATERIAL AND METHODS: ACN III biopsy core needles 14 gauge x
      160 mm with automatic pistol device were used on three bodies dedicated to
      research from the local anatomical institute. Tissue probes from the brain,
      heart, lung, liver, spleen, kidney and muscle tissue were obtained under CT
      fluoroscopy. RESULTS: CT fluoroscopy enabled accurate placement of the needle
      within the organs and tissues. The needles allowed for sampling of tissue probes
      with a mean width of 1.7 mm (range 1.2-2 mm) and the maximal length of 20 mm at
      all locations. The obtained tissue specimens were of sufficient size and adequate
      quality for histological analysis. CONCLUSION: Our results indicate that, similar
      to the clinical experience but in many more organs, the tissue specimens obtained
      using the clinically approved biopsy needle are of a sufficient size and adequate
      quality for a histological examination. We suggest that post-mortem biopsy using
      the ACN III needle under CT guidance may become a reliable method for targeted
      sampling of tissue probes of the body.

PMID- 16814506
TI  - Neurologic manifestations and treatment of Henoch-Schonlein purpura.

PMID- 16814507
TI  - Telomerase as a clinical target: current strategies and potential applications.
AB  - Chromosome ends are capped by telomeres, protective DNA-protein complexes that
      distinguish natural ends from random DNA breaks. Telomeres erode with each
      successive cell division, and such divisions cease once telomeres become
      critically short. This proliferation limit is important as a tumor suppressive
      mechanism, but also contributes to the degenerative conditions associated with
      cellular aging. In cell types that require continuous renewal, transient
      expression of telomerase delays proliferation arrest by the de novo synthesis of
      telomere repeats. Data from our work and others' has shown that deficient
      telomerase activity has a negative impact on normal human physiology. In the bone
      marrow failure syndrome dyskeratosis congenita, telomerase enzyme deficiency
      leads to the premature shortening of telomeres. Premature telomere shortening
      most grievously affects tissues that have a rapid turnover, such as the
      hematopoietic and epithelial compartments. In the most severe cases, compromised
      renewal of hematopoietic stem cells leads to bone marrow failure and premature
      death. Telomerase activation/replacement shows potential as a therapy for
      telomere maintenance deficiency syndromes, and in tissue engineering for the
      degenerative conditions that are associated with normal aging. Conversely,
      clinical researchers are developing telomerase inhibition therapies to treat
      tumors, which overcome the short-telomere barrier to unrestricted proliferation
      by over-expressing telomerase.

PMID- 16814508
TI  - Aging cellular networks: chaperones as major participants.
AB  - We increasingly rely on the network approach to understand the complexity of
      cellular functions. Chaperones (heat shock proteins) are key "networkers", which
      sequester and repair damaged proteins. In order to link the network approach and
      chaperones with the aging process, we first summarize the properties of aging
      networks suggesting a "weak link theory of aging". This theory suggests that age
      related random damage primarily affects the overwhelming majority of the low
      affinity, transient interactions (weak links) in cellular networks leading to
      increased noise, destabilization and diversity. These processes may be further
      amplified by age-specific network remodelling and by the sequestration of weakly
      linked cellular proteins to protein aggregates of aging cells. Chaperones are
      weakly linked hubs (i.e., network elements with a large number of connections)
      and inter-modular bridge elements of protein-protein interaction, signalling and
      mitochondrial networks. As aging proceeds, the increased overload of damaged
      proteins is an especially important element contributing to cellular
      disintegration and destabilization. Additionally, chaperone overload may
      contribute to the increase of "noise" in aging cells, which leads to an increased
      stochastic resonance resulting in a deficient discrimination between signals and
      noise. Chaperone- and other multi-target therapies, which restore the missing
      weak links in aging cellular networks, may emerge as important anti-aging
      interventions.

PMID- 16814509
TI  - Tissue culture of ornamental pot plant: a critical review on present scenario and
      future prospects.
AB  - Recent modern techniques of propagation have been developed which could help
      growers to meet the demand of the horticultural industry in the next century. An
      overview on the in vitro propagation via thin cell layer, meristem culture,
      regeneration via organogenesis and somatic embryogenesis is presented. Available
      methods for the transfer of genes could significantly simplify the breeding
      procedures and overcome some of the agronomic and environmental problems, which
      other wise would not be achievable through conventional propagation methods. The
      development and remarkable achievements with biotechnology in ornamental pot
      plants made during the three decades have been reviewed. The usefulness of the
      pot plants in commercial industry as well as propagation techniques, screening
      for various useful characteristics and selection of somaclonal variation is also
      discussed.

PMID- 16814510
TI  - Promoting adolescents' use of medical services.

PMID- 16814511
TI  - Axillary staging in women with small invasive breast tumours.
AB  - AIMS: To identify a group of women with small breast cancers of favourable
      histological grade for whom observation alone may be an acceptable approach for
      management of the axilla. METHODS: In a retrospective analysis the incidence of
      nodal metastases was examined in a group of 355 consecutive patients over 55
      years of age who underwent mastectomy or breast conserving surgery. All patients
      had either grade I (<20 mm) or grade II (<15 mm) oestrogen receptor positive
      tumours without lymphovascular invasion (LVI). In a related study on 173
      clinically node negative patients, the rate of axillary recurrence was assessed
      in patients with small (<10 mm), non-high grade (I and II), ER-positive invasive
      ductal carcinomas without LVI. Axillary surgery was either omitted (135 patients)
      or delayed (38 patients) at the time of wide local excision or mastectomy.
      RESULTS: The overall incidence of positive nodes in this good prognostic group of
      patients was 13% (95% confidence interval 9.5-16.5). When the analysis was
      confined to grade I (< or =20 mm) and grade II (< or =10 mm) the overall
      incidence of nodal metastases was 10%. Rates of axillary recurrence at a median
      follow up of 49 months were only 1% when axillary surgery was omitted according
      to patient choice/departmental policy with no cases of uncontrolled axillary
      recurrence. CONCLUSION: The risk:benefit ratio for detection of node positive
      cases in a selected group of older patients does not justify any form of axillary
      procedure at the time of primary surgery.

PMID- 16814512
TI  - [Gastric foreign body. Rare complication of nasogastric tube placing].
AB  - The use of an uncuffed endotracheal tube for the placement of nasogastric tubes
      during surgery is not a procedure free of any risk. We report a rare case of
      gastric foreign body secondary to this procedure. A 67-year-old patient who had
      underwent a coronary bypass for a three vessels disease two years before
      complained of postprandial epigastralgia lasting for a few months. The
      investigations reported a gastric ulcer associated with a tubular gastric foreign
      body. The endoscopic extraction found an endotracheal tube. It is a common habit
      in our institution to use this method when placing this tube through a nostril in
      order to ease the nasogastric tube insertion when it is difficult.

PMID- 16814513
TI  - [Early and late management of oral antiplatelet agents after coronary stenting].

PMID- 16814514
TI  - To look or not to look at threat? Scanpath differences within a group of spider
      phobics.
AB  - Predicting the behavior of phobic patients in a confrontational situation is
      challenging. While avoidance as a major clinical component of phobias suggests
      that patients orient away from threat, findings based on cognitive paradigms
      indicate an attentional bias towards threat. Here we present eye movement data
      from 21 spider phobics and 21 control subjects, based on 3 basic oculomotor tasks
      and a visual exploration task that included close-up views of spiders. Relative
      to the control group, patients showed accelerated reflexive saccades in one of
      the basic oculomotor tasks, while the fear-relevant exploration task evoked a
      general slowing in their scanning behavior and pronounced oculomotor avoidance.
      However, this avoidance strongly varied within the patient group and was not
      associated with the scores from spider avoidance-sensitive questionnaire scales.
      We suggest that variation of oculomotor avoidance between phobics reflects
      different strategies of how they cope with threat in confrontational situations.

PMID- 16814515
TI  - Stereotypy in young children with autism and typically developing children.
AB  - Although stereotypy is one of the key diagnostic features of autism, few studies
      have compared stereotypic behavior in children with autism and typically
      developing children. The present study employed direct observational measurement
      methods to assess levels of stereotypic behavior in 2-, 3- and 4-year-old
      children with autism or pervasive developmental disorder - not otherwise
      specified (PDD-NOS) and age-matched typically developing peers. Thirty children
      with autism or PDD-NOS and 30 typically developing children participated. Each
      child's performance of several early learning and play skills was assessed using
      a direct observational assessment protocol developed for children with autism who
      were entering early intensive behavioral treatment. Duration of episodes of vocal
      and motor stereotypy was recorded from a videotaped 10 min portion of that
      assessment session. Results indicated that the 2-year-old children with autism or
      PDD-NOS had somewhat higher levels of stereotypic behavior than the typically
      developing 2-year-olds, while the 3- and 4-year-old children with autism or PDD
      NOS displayed substantially higher levels stereotypic behavior than their same
      age peers.

PMID- 16814516
TI  - A zebrafish assay for identifying neuroprotectants in vivo.
AB  - In this study, we developed an in vivo method to determine drug effects on
      oxidation-induced apoptosis in the zebrafish brain caused by treatment with L
      hydroxyglutaric acid (LGA). We confirmed that LGA-induced apoptosis was caused by
      oxidation by examining the presence of an oxidative product, nitrotyrosine. Next,
      we examined the effects of 14 characterized neuroprotectants on LGA-treated
      zebrafish, including: D-methionine (D-Met), Indole-3-carbinol, deferoxamine
      (DFO), dihydroxybenzoate (DHB), deprenyl, L-NAME (N(G)-nitro-L-arginine methyl
      ester), n-acetyl L-cysteine (L-NAC), 2-oxothiazolidine-4-carboxylate (OTC),
      lipoic acid, minocycline, isatin, cortisone, ascorbic acid and alpha-tocopherol.
      Eleven of 14 neuroprotectants and 7 of 7 synthetic anti-oxidants exhibit
      significant protection in zebrafish. Buthionine sulfoximine (BSO), used as a
      negative control, exhibited no significant protective effects. In addition, three
      blood-brain barrier (BBB) impermeable compounds exhibited no significant effects.
      Our results in zebrafish were similar to results reported in mammals supporting
      the utility of this in vivo method for identifying potential neuroprotective anti
      oxidants.

PMID- 16814517
TI  - Is pyruvate an endogenous anti-inflammatory molecule?
AB  - Pyruvic acid is an effective scavenger of reactive oxygen species. Ethyl pyruvate
      has demonstrated anti-inflammatory actions and improved hyperpermeability and
      bacterial translocation due to endotoxemia and is of benefit in animal models of
      sepsis and septic shock. Ethyl pyruvate specifically inhibits tumor necrosis
      factor-alpha production and decreases circulating levels of high-mobility group
      box-1 and nuclear factor-kappaB signaling pathways by specifically targeting its
      p65 subunit in animals with established endotoxemia or sepsis and in macrophage
      cultures. Ethyl pyruvate also decreases cyclo-oxygenase-2, inducible nitric oxide
      synthase, and interleukin-6 mRNA expression in the liver, ileal mucosa, and
      colonic mucosa in animal models with hemorrhagic shock. Similar beneficial
      actions have been seen in endotoxemia. These and other studies suggest that ethyl
      pyruvate could be of significant benefit in the treatment of patients who are
      critically ill and have sepsis/septic shock.

PMID- 16814518
TI  - Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity
      on human colorectal adenocarcinoma cells.
AB  - OBJECTIVE: This study evaluated whether omega-3 polyunsaturated fatty acids
      (PUFAs) could enhance the radiosensitivity of three different human colorectal
      adenocarcinoma cell lines. To understand the underlying mechanisms, the effects
      of omega-3 PUFAs on the cell growth, survival, and apoptosis were evaluated alone
      or in combination with an antioxidant (vitamin E) and compared with the effects
      of omega-6 PUFAs. METHODS: LS174T, CO112, and Caco-2 cell survival was assessed
      by clonogenic assay after a 3-d pretreatment with omega-3/omega-6 PUFAs and/or
      vitamin E before a single X-ray exposure to 4 Gy. Cell growth and viability were
      measured by double fluorescence-activated cell sorter analyses using propidium
      iodide and fluorescein isothiocyanate-conjugated annexin V. Student's t test or
      multivariable linear regression analyses were used for comparison. RESULTS:
      Preincubation with 30 to 100 micromol/L of omega-3 PUFAs induced a dose-dependent
      additive decrease in cell survival after irradiation (P < 0.05). Evaluation of
      the underlying mechanisms indicated that omega-3 PUFAs mainly decreased the cell
      number via apoptosis induction. Moreover, formation of lipid peroxidation
      products and modulation of cyclooxygenase II activity seemed to be involved,
      because coincubation with 10 micromol/L vitamin E abolished the effect of 50
      micromol/L of omega-3 PUFAs (P < 0.05), whereas omega-6 PUFAs could partly mimic
      omega-3 PUFA effects. CONCLUSION: These observations suggest that omega-3 PUFAs
      may be potential candidates as nutritional adjuvants to enhance the efficacy of
      human colorectal cancer radiotherapy.

PMID- 16814519
TI  - Cecal parameters of rats fed diets containing grapefruit polyphenols and inulin
      as single supplements or in a combination.
AB  - OBJECTIVE: We compared the effects of grapefruit flavonoids and inulin, as single
      dietary components or in a combination, on cecal fermentation in rats adapted to
      a semipurified diet. METHODS: The experimental diets contained 0.3% flavonoid
      extract and 5% or 10% inulin and a combination of both supplements. The large
      bowel metabolism assessment was based on cecal parameters: bulk effect, pH,
      microbial enzymes activity, and short-chain fatty acid production. RESULTS: Both
      supplements induced significant enlargement of the cecal digesta weight.
      Acidification of cecal digesta was more pronounced, with a higher inulin addition
      to the diet. Cecal pH was the highest with the flavonoid-rich diets and lowest in
      the case of a simultaneous addition of flavonoids and a high content of inulin.
      The flavonoid extract applied as a single dietary supplement was observed to
      decrease the activity of bacterial beta-glucosidase and beta- and alpha
      galactosidases in the cecal digesta. In contrast, addition of the grapefruit
      extract to inulin-containing diets increased the activity of alpha-glucosidase,
      alpha-galactosidase, and beta-galactosidase. Great accumulation of cecal digesta
      in rats consuming the flavonoid-diet caused a considerable increase in the short
      chain fatty acid pool, mainly acetic acid. Inulin added to the diet decreased the
      excessive enlargement of digesta caused by dietary flavonoids. Dietary addition
      of inulin to the flavonoid-diet also normalized hydration of cecal digesta and
      significantly decreased the pH of digesta. The presence of polyphenols in the
      inulin-containing diets did not change total short-chain fatty acid production in
      the cecum of rats. CONCLUSION: Our results suggested that simultaneous intake of
      inulin and polyphenols can decrease the detrimental effects of the latter on
      cecal fermentation.

PMID- 16814520
TI  - Classification of benign infantile afebrile seizures.
AB  - PURPOSE: The aim of this study is to classify infantile cases with benign
      seizures into known epileptic syndromes, thereby facilitating discussion of
      clinical factors that could play an important role in diagnosis. SUBJECTS: Fifty
      seven patients with afebrile seizures fulfilling all of the following criteria
      were enrolled: (1) normal development prior to the onset, (2) no underlying
      disorders nor neurological abnormalities, (3) onset before the age of four and
      (4) normal interictal EEG and neuroimaging findings. RESULTS: Thirty-nine cases
      (Group A) were characterized by an association of mild gastroenteritis. The
      remaining 18 cases were divided into two groups according to the seizure type.
      One group had partial seizures (Group B, 13 cases) while the other was suspected
      to have generalized seizures (Group C, 5 cases). Age at onset was significantly
      higher for Group A (19.5 +/- 5.5 months) than Groups B (5.3 +/- 1.8 months)
      (p<0.001) and C (5.8 +/- 3.5 months) (p=0.038). Positive family history of
      seizure disorder, seizure cluster tendency, and the efficacy of lidocaine against
      seizure clusters were common in the three groups. CONCLUSIONS: Features in Group
      A were consistent with benign convulsions with mild gastroenteritis (proposed by
      Morooka) [Morooka, K., 1982. Mild diarrhea and convulsions. Shonika 23, 134-137
      (in Japanese)], those of Group B with benign partial epilepsy in infancy
      [Watanabe, K., Yamamoto, N., Negoro, T., Takaesu, E., Aso, K., Furune, S.,
      Takahashi, I., 1987. Benign complex partial epilepsies in infancy. Pediatr.
      Neurol. 3, 208-211], and those of Group C with benign infantile convulsions
      [Fukuyama, Y., 1963. Borderland of epilepsy with special reference to febrile
      convulsions and so-called infantile convulsions. Seishin Igaku 5, 211-223 (in
      Japanese)]. The distinction between these syndromes depends upon age at onset,
      association with gastroenteritis, and ictal symptomatology. In our experience,
      however, it was not easy to catch seizure type accurately in clinical situations.
      As far as the results of ictal video-EEG monitoring ever carried out concern,
      focal initiation of parxysmal discharges was demonstrated in all cases, not only
      of BPEI but also of apparent generalized seizures examined without exception.
      These observations led the authors to conclude that the identity of BIC is
      dubious, most probably it will represent a subtype of BPEI.

PMID- 16814521
TI  - Open label, long-term, pragmatic study on levetiracetam in the treatment of
      juvenile myoclonic epilepsy.
AB  - PURPOSE: Patients with juvenile myoclonic epilepsy (JME) may be resistant or show
      adverse effects to valproate. We present a multicenter, prospective, long-term,
      open-label study evaluating the efficacy and safety of levetiracetam in JME.
      METHODS: Patients with newly diagnosed (10) or resistant/intolerant to previous
      AEDs JME (38) were enrolled. After a 8 week baseline period, levetiracetam was
      titrated in 2 weeks to 500 mg b.i.d. and then increased up to 3000 mg/day
      according to the patient's response. Efficacy parameters were: number of seizure
      free patients, number of days with myoclonus (DWM), and monthly frequency of
      generalised tonic-clonic (GTC) seizures. Adverse events were recorded. RESULTS:
      The overall mean dose of levetiracetam was 2208 mg/day. The mean study period was
      19 (range 0.3-38) months. Five patients dropped out. 11/38 (28.9%) patients with
      add-on treatment and 5/10 (50%) newly diagnosed patients were seizure-free for a
      mean period of 17.2 (+/-8.8) months. Eighteen patients (37.5%) were without
      myoclonia, and 35 (72.9%) had no GTC seizures over the study period. The mean
      monthly frequency of DWM and of GTC seizures in the entire group was
      significantly reduced after levetiracetam. Five patients complained of side
      effects. CONCLUSIONS: This open-label study suggests levetiracetam may be
      effective and well tolerated in resistant cases of JME or may become a reasonable
      alternative to valproate in newly diagnosed patients.

PMID- 16814522
TI  - Photosensitivity, visually sensitive seizures and epilepsies.
AB  - Although many observations in patients with this intriguing type of epilepsy have
      been described and detailed studies have been performed, only a few meet the
      current criteria of class 1 or 2 evidence-based studies. In general, the
      selection bias is due to studying a referral population instead of the general
      population, and to different age and sex distributions of the subjects under
      study. Comparing the various studies is often difficult, because of differences
      in the populations studied (single seizures, epilepsy centre population, etc.),
      but also because of different methods (photic stimulator, flash frequencies, eye
      conditions, etc.) and the terminology used. Finally, and most crucial, in many
      studies there is often no information on how the data were actually obtained (EEG
      or clinical data or both?). The popular term "photosensitive" is used widely and
      applied to patients with a history of visually induced seizures, with and without
      a photoparoxysmal response (PPR), and to those with only a PPR. An overview of
      the "hard" data is given with future needs for a better understanding of this
      type of epilepsy and for improving the endophenotype for genetic research. It is
      important to standardise the studies as much as possible and describe in detail
      the methodology of the study, taking at least the above variables into account.

PMID- 16814523
TI  - The clinical-electrographic expression of infantile seizures.
AB  - PURPOSE: To describe the electro-clinical expression of seizures in infants (1-24
      months). METHODS: We reviewed the video and EEG files of all infantile seizures
      recorded at Children's Memorial Hospital, Chicago, IL, from 2000 to 2005.
      Electrographic and clinical features were entered into separate databases. The
      electrographic component of the database analyzed the predominant location and
      pattern at onset, the evolution, the termination and the duration of each
      seizure. The clinical data sheet included 25 items. Each seizure was assigned to
      a specific category according to its most prominent clinical feature, according
      to the opinion of both observers. RESULTS: Thirteen seizure types were
      identified. In a significant number of cases, the EEG correlate could not be
      predicted on the basis of clinical observations only. Generalized seizures were
      observed, on average, at a later age than focal seizures. Excluding spasms, the
      mean duration of seizures was short (36 s). CONCLUSIONS: The results of this
      study are useful in describing the clinical and electrographic repertoire of
      infantile seizures. The findings show that video-EEG recordings in infants with
      frequent, recurrent seizures are useful by fully allowing complete recognition of
      subtle events, and in fully categorizing the true nature of the ictus. Video-EEG
      findings and accurate seizure classification may add fundamental information with
      regards to epilepsy syndrome diagnosis and specific treatment options, including
      surgery.

PMID- 16814524
TI  - Does smoking reduce akathisia? Testing a narrow version of the self-medication
      hypothesis.
AB  - BACKGROUND: The self-medication hypothesis proposes that schizophrenia patients
      smoke to decrease their schizophrenia symptoms or antipsychotic side effects, but
      they usually start smoking before their illness and heavy smoking is not
      consistently associated with fewer symptoms or side effects. A narrow version of
      the self-medication hypothesis, heavy smoking reduces akathisia, is explored.
      METHOD: The sample included 250 outpatients with DSM-IV schizophrenia assessed
      with the Positive and Negative Syndrome Scale (PANSS) and the Barnes Akathisia
      Scale. Prevalences were 69% (173/250) for smoking, 39% (98/250) for heavy smoking
      (> or =30 cigarettes/day), 7% (17/250) for akathisia (Barnes Global score>1), 14%
      (35/250) for a broader akathisia definition (Barnes Global score>0) and 20% for
      excited symptoms (>1 on the PANSS factor score). RESULTS: Heavy smoking was not
      associated with akathisia (41% of patients with akathisia were heavy smokers
      versus 39% of patients without akathisia; chi2=0.3, df=1, p=0.86), even after
      correcting for confounding factors and/or using a broader akathisia definition.
      Heavy smoking was associated with excited schizophrenia symptoms (possibly
      reflecting agitation). Particularly in patients taking lower doses of typical
      antipsychotics, excited symptoms, with or without akathisia, were strongly
      associated with heavy smoking and appear to interact with patients' reports of
      smoking's calming effect as the main reason for smoking. CONCLUSION: The self
      medication hypothesis does not explain increased smoking and heavy smoking in
      schizophrenia. Moreover, heavy smoking may be associated with more disturbed
      brain homeostatic mechanisms. Prospective studies need to explore whether
      temporary increases in cigarette smoking may be associated with periods of higher
      agitation, with or without akathisia.

PMID- 16814526
TI  - Functional adaptation skills training (FAST): a randomized trial of a
      psychosocial intervention for middle-aged and older patients with chronic
      psychotic disorders.
AB  - OBJECTIVE: Behavioral interventions designed to improve functioning of older
      patients with schizophrenia and other chronic psychotic disorders have the
      potential to significantly increase patients' independence and quality of life.
      This study evaluated a psychosocial intervention designed to improve everyday
      living skills of middle-aged and older outpatients with chronic psychotic
      disorders. METHODS: A total of 240 patients with a DSM-IV-based chart diagnosis
      of schizophrenia or schizoaffective disorder participated in a 24-week,
      randomized controlled trial comparing a behavioral group intervention called
      "Functional Adaptations and Skills Training" (FAST; n=124) to a time-equivalent
      attention-control (AC; n=116) group focused on improving functional skills.
      RESULTS: Compared to participants randomized to AC, those in the FAST
      intervention demonstrated significant improvement in everyday living skills
      (p=.046) and social skills (p=.003), but not medication management skills
      (p=.268). CONCLUSIONS: Results suggest that middle-aged and older patients with
      psychotic disorders may benefit from participation in interventions designed
      specifically to improve functional skills.

PMID- 16814525
TI  - Functional magnetic resonance imaging of internal source monitoring in
      schizophrenia: recognition with and without recollection.
AB  - Patients with schizophrenia tend to have impaired source monitoring and intact
      item recognition, suggesting an over-reliance of familiarity effects. We
      previously demonstrated that providing patients with a levels-of-processing (LOP)
      semantic encoding strategy normalized source monitoring. The current blood-oxygen
      level-dependent (BOLD) functional magnetic resonance imaging (fMRI) study tests
      the hypothesis that patients will have abnormally increased fronto-temporal
      activation despite intact performance. fMRI was measured in 13 patients and 13
      demographically matched healthy controls during a LOP source monitoring paradigm.
      SPM2 was used for standard pre-processing and statistical analyses, with a
      corrected significance threshold of p<.05. Examination of accuracy and speed
      measures did not reveal any group differences in task performance. Regardless of
      source retrieval success both groups activated expected prefrontal and parietal
      regions, with no areas of relatively greater control versus patient activation.
      In support of the hypothesis, patients showed abnormally increased activation in
      temporolimbic areas including middle and superior temporal gyrus, thalamus, and
      parahippocampal gyrus. Activation in these areas was associated with worse
      positive and negative symptoms, but did not correlate with performance,
      suggesting inefficient rather than compensatory activation.

PMID- 16814527
TI  - Single nucleotide polymorphism in a commonly utilized LAMB3 primer sequence:
      implications for mutation detection and haplotype analysis in junctional
      epidermolysis bullosa.

PMID- 16814528
TI  - Structure, folding, and misfolding of Cu,Zn superoxide dismutase in amyotrophic
      lateral sclerosis.
AB  - Fourteen years after the discovery that mutations in Cu, Zn superoxide dismutase
      (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS), the
      mechanism by which mutant SOD1 exerts toxicity remains unknown. The two principle
      hypotheses are (a) oxidative damage stemming from aberrant SOD1 redox chemistry,
      and (b) misfolding of the mutant protein. Here we review the structure and
      function of wild-type SOD1, as well as the changes to the structure and function
      in mutant SOD1. The relative merits of the two hypotheses are compared and a
      common unifying principle is outlined. Lastly, the potential for therapies
      targeting SOD1 misfolding is discussed.

PMID- 16814529
TI  - The effect of solvent polarity on the molecular surface properties and adhesion
      of Escherichia coli.
AB  - The elasticity and molecular surface characteristics of Escherichia coli JM109
      were investigated via atomic force microscopy (AFM) in solvents expressing
      different polarities. The nature of bacterial adhesion and surface
      characteristics was probed in formamide, water, and methanol, with dielectric
      constants of 111, 80, and 33, respectively. Solvent polarity affected the
      elasticity of the bacterium, the conformation of the cell surface biopolymers,
      the height of the surface biopolymers, and measured adhesion forces between the
      bacterium and silicon nitride. By applying the Hertz model to force-indentation
      data, we determined that the Young's modulus was greatest in the least polar
      solvent, with values of 182 +/- 34.6, 12.8 +/- 0.1, and 0.8 +/- 0.3 MPa in
      methanol, water, and formamide, respectively. The thickness of the biopolymer
      brush layer on the bacterial surface was quantified using a steric model, and
      these values increased as polarity increased, with values of 27, 93, and 257 nm
      in methanol, water, and formamide, respectively. The latter results suggest that
      highly polar conditions favor extension of the biopolymer brush layer. Cross
      sectional analysis performed on tapping mode images of the bacterial cells in
      methanol, water, and formamide further supported this hypothesis. The image
      height values are larger, since the image analysis measures the height of the
      bacterium and the polymer layer, but the trend with respect to solvent polarity
      was the same as was obtained from the steric model of the brush length. Measured
      adhesion forces scaled inversely with solvent polarity, with greatest adhesion
      observed in the least polar solvent, methanol. The combined conformational
      changes to the bacterial surface and biopolymer layer result in different
      presentations of macromolecules to a substrate surface, and therefore affect the
      adhesion forces between the bacterial molecules and the substrate. These results
      suggest that polarity of the solvent environment can be manipulated as a design
      parameter to control or modify the bacterial adhesion process.

PMID- 16814530
TI  - Vitamin E biokinetics, oxidative stress and cigarette smoking.
AB  - Vitamin E is comprised of four tocopherols and four tocotrienols, and functions
      as a lipophilic chain-breaking antioxidant that prevents lipid peroxidation.
      Although it is well recognized that cigarette smoke is source of oxidative
      stress, relatively little is known regarding how oxidative stress alters vitamin
      E utilization in humans. Therefore, this review will highlight the recent
      knowledge regarding how cigarette smoking alters vitamin E (as alpha- and gamma
      tocopherols) utilization in humans. Specifically, we will discuss the mechanisms
      by which cigarette smoking increases the turnover of plasma vitamin E, decreases
      the P450-mediated metabolism of vitamin E, and increases the nitration of gamma
      tocopherol to result in the formation of 5-nitro-gamma-tocopherol. In addition,
      the interrelationship between oxidative stress and vitamin C will also be
      emphasized as it relates to vitamin E utilization.

PMID- 16814531
TI  - [Off label drugs and pediatric hematology-oncology practices].

PMID- 16814532
TI  - pH-independent pulsatile drug delivery system based on hard gelatin capsules and
      coated with aqueous dispersion Aquacoat ECD.
AB  - The objective of this study was to develop a rupturable, capsule-based pulsatile
      drug delivery system with pH-independent properties prepared using aqueous
      coating. The drug release is induced by rupturing of the top-coating, resulting
      by expanding of swellable layer upon water penetration through the top-coating.
      Croscarmellose sodium (AcDiSol) is a preferable superdisintegrant compared to low
      substituted hydroxypropylcellulose (L-HPC) and sodium starch glycolate
      (Explotab), because of controlled lag time, followed by a quick and complete drug
      release. However, due to its anionic character, AcDiSol showed pH-dependent
      swelling characteristics (pH 7.4 > 0.1N HCl) resulting in a pH-dependent lag
      time. The pH dependency could be eliminated by the addition of fumaric acid to
      the swelling layer, which allowed to keep an acidic micro-environment. Formation
      of the rupturable top-coating was successfully performed using an aqueous
      dispersion of ethylcellulose (Aquacoat) ECD), whereby sufficient drying during
      the coating was needed to avoid swelling of the AcDiSol layer. A higher coating
      level was required, when aqueous dispersion was used, compared to organic
      coatings. However, an advantageous aspect of the aqueous coating was the lower
      sensitivity of the lag time to a deviation in the coating level.

PMID- 16814533
TI  - Hormonal induction of ovulation stimulates atresia of antral follicles in a
      vespertilionid bat, Scotophilus heathi.
AB  - Scotophilus heathi is a seasonally monoestrous subtropical vespertilionid bat
      found at Varanasi, India. Although the antral follicles remain present in the
      ovaries of S. heathi from November till March, ovulation is delayed in this
      species until early March. In order to understand the mechanism of ovulation
      suppression during this period of delayed ovulation, the effects of human
      chorionic gonadotropin (hCG), pregnant mare's serum gonadotropin (PMSG), follicle
      stimulating hormone (FSH) and gonadotropin releasing hormone agonist (GnRH
      agonist) on ovarian morphology and steroid concentration were investigated.
      Hormonal treatments were given as a single i.p. dose 24 h after capture. The bats
      were sacrificed 48 h after the injection. Treatment with hCG, PMSG, FSH and GnRH
      agonist failed to induce ovulation in S. heathi, although these hormones produced
      a high degree of ovarian stimulation. The administration of hCG and PMSG induced
      ovarian enlargement, intense hyperemia, marked changes in the interstitial cells
      (ICs), development of several antral follicles and a varying degree of
      abnormalities in the oocytes of most of the antral follicles. In the bats treated
      with hCG, PMSG and GnRH agonist, androstenedione concentration increased
      significantly to extraordinarily high levels, whereas estradiol concentration
      decreased. Administration of FSH caused regression of ICs and pyknosis of
      granulosa cells in the majority of antral follicles. FSH did not enhance
      androstenedione concentration. The results of the present study suggest that the
      failure of hormonal treatments to induce ovulation during the period of delayed
      ovulation might be due to a seasonal desensitization of ovarian follicles in S.
      heathi. The hormonal treatment instead stimulated the ICs to produce a high level
      of androstenedione resulting in atretic changes of the antral follicles.

PMID- 16814535
TI  - WITHDRAWN: Letter to the Editor.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 16814534
TI  - Impacts of 2,4-D application on soil microbial community structure and on
      populations associated with 2,4-D degradation.
AB  - The effect of 2,4-dichlorophenoxyacetic acid (2,4-D) application rate on
      microbial community structure and on the diversity of dominant 2,4-D degrading
      bacteria in an agricultural soil was examined using cultivation-independent
      molecular techniques coupled with traditional isolation and enumeration methods.
      Fingerprints of microbial communities established under increasing concentrations
      of 2,4-D (0-500 mg kg-1) in batch soil microcosms were obtained using denaturing
      gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA gene segments.
      While a 2,4-D concentration of at least 100 mg kg-1 was required to obtain an
      apparent change in the community structure as visualized by DGGE, the greatest
      impact of 2,4-D concentration occurred in the 500 mg kg-1 treatment, resulting in
      significantly reduced diversity of the dominant populations and enrichment by
      Burkholderia-like populations. The greatest diversity of 2,4-D degrading isolates
      was cultivated from the 10 mg kg-1 treatment, indicating that under these
      conditions, cultivation was more sensitive than DGGE for detecting changes in
      community structure. Most of these isolates harbored homologs of Ralstonia
      eutrophus JMP134 and Burkholderia cepacia tfdA catabolic genes. Results from this
      study revealed that agriculturally relevant application rates of 2,4-D may
      provide a temporary selective advantage for organisms capable of utilizing 2,4-D
      as a carbon and energy source.

PMID- 16814536
TI  - Colonization of Sitka spruce stumps by decay-causing hymenomycetes in paired
      inoculations.
AB  - Sitka spruce stumps were inoculated with decay fungi using colonized sawdust or
      dowel inoculum to investigate colonization in paired combinations. Estimates of
      domain sizes were made in the top 15cm of stump after 13-14 or 21-23 months with
      sawdust or dowel inoculations, respectively. None of the co-inoculated species
      prevented colonization by Heterobasidion annosum; sapwood colonization by
      Resinicium bicolor may limit growth of H. annosum colonies out of heartwood,
      reducing the incidence of disease transfer at root contacts. H. annosum colonized
      stumps despite the presence of competing inoculum. Reduced colonization occurred
      in paired inoculations with R. bicolor, but not with other fungi. Co-inoculations
      with Stereum sanguinolentum increased colonization by H. annosum. R. bicolor
      largely remained in the upper 3-4cm of stumps and reduced colonization by
      Melanotus proteus; growth of S. sanguinolentum was completely prevented. The
      results are discussed in relation to the colonization strategies of the decay
      fungi, their ability to colonize stumps in the presence of competitors and
      factors influencing development of communities of decay fungi in stumps.

PMID- 16814537
TI  - Evaluation of a transcutaneous carbon dioxide monitor ("TOSCA") in adult patients
      in routine respiratory practice.
AB  - BACKGROUND: Non-invasive measurement of oxygenation is routine in adult clinical
      practice but transcutaneous monitoring of PCO(2) (PtcCO(2)) is used much less due
      to technical difficulties with earlier transcutaneous electrodes. OBJECTIVE: Our
      aim was to determine the reliability of estimating arterial PCO(2) (PaCO(2))
      using a recently introduced combined SaO(2)/PtcCO(2) monitor ("TOSCA", Linde
      Medical Systems) in adult patients in routine clinical respiratory practice.
      METHODS: PtcCO(2) was measured in patients requiring arterial blood gases for
      clinical reasons. Ten minutes after the probe had been attached to an earlobe
      PtcCO(2) was recorded, immediately before arterial blood sampling. The PCO(2)
      values obtained were compared by Bland-Altman analysis. RESULTS: Samples were
      taken from 48 unselected patients with varied pathology. There were no technical
      problems. Median age was 56 years (range 20-86 years). The mean difference
      between PaCO(2) and PtcCO(2) was -0.04kPa, sd of the difference 0.67kPa. Bland
      Altman analysis showed generally good agreement between the two measurements
      across the range of PaCO(2) values (4-10.9kPa). Four of 48 measurements showed a
      PCO(2) difference >1kPa with no technical or clinical explanations apparent.
      CONCLUSIONS: The accuracy of estimation of PaCO(2) by the TOSCA transcutaneous
      electrode was generally good and the device appears promising for use in routine
      clinical respiratory practice.

PMID- 16814538
TI  - Exposure to environmental tobacco smoke in a general population.
AB  - AIMS: To estimate how the level of exposure to environmental tobacco smoke (ETS)
      in pregnancy, childhood and adulthood vary with personal characteristics in a
      general population. METHODS: In 1996/1997, a community sample of 3181 adults,
      aged 26-82, received a mailed questionnaire, to which 2819 subjects responded.
      The prevalences of ETS exposure were estimated according to sex, age, educational
      level, smoking, occupational dust or gas exposure and exposure to moulds.
      Logistic regression was used to estimate the adjusted odds ratios for the
      different ETS exposures with respect to these covariates. RESULTS: Altogether 9%
      reported exposure to maternal smoking in foetal life and 23% in childhood.
      Fourteen percent reported current domestic ETS exposure, while 13% reported
      current occupational ETS. Occupational ETS exposure was more frequent among men
      (16%) than women (10%). The oldest subjects (61-82 years) reported less ETS
      exposures than the younger subjects. Current smokers and subjects with
      occupational dust or fumes exposure had a higher prevalence for all the ETS
      exposures compared to ex- and never smokers and subjects without occupational
      exposure, respectively. CONCLUSION: From a general population sample male sex,
      younger age, current smoking, and occupational dust or fumes exposure were
      associated with higher level of ETS exposure.

PMID- 16814540
TI  - The ClC family of chloride channels and transporters.
AB  - The ClC proteins are members of a large family of chloride transport proteins,
      which are involved in a variety of physiological processes. All family members
      share a conserved molecular architecture consisting of a complex transmembrane
      transport domain and a soluble regulatory domain. To date, representative
      structures for the two parts are available, the transmembrane domain from the
      structure of a bacterial homologue, the soluble domain from a eukaryotic family
      member. Despite the strong conservation of the structural framework, the family
      members show an unusually broad variety of functional behaviors, as some members
      work as gated chloride channels and others as secondary chloride transporters.
      The conservation in the structure and the functional resemblance in gating and
      transport mechanism suggest a strong mechanistic relationship between seemingly
      contradictory transport modes.

PMID- 16814541
TI  - Lessons from Coley's Toxin.
AB  - The active molecule in Coley's Toxin is not tumor necrosis factor (TNF) or
      endotoxin (LPS), but interleukin-12 (IL-12). IL-12 holds the key to improved anti
      tumor immuns response.

PMID- 16814543
TI  - Synthesis and receptor binding properties of chimeric peptides containing a mu
      opioid receptor ligand and nociceptin/orphanin FQ receptor ligand Ac-RYYRIK
      amide.
AB  - Four chimera peptides composed of ORL1 receptor ligand Ac-RYYRIK-NH2 and a mu
      opioid receptor agonist dermorphin YAFGYPS-NH2 or YRFB-NH2, with a spacer linking
      the two pharmacophores, were synthesized and tested for their receptor binding
      properties. Chimera peptides with long spacers (a Lys and five or eight Gly
      residues) showed synergistically improved affinity for both the mu-opioid
      receptor and ORL1 receptor, while the chimera peptides with short spacers (Lys
      residue only) showed decreased or similar affinity compared to the monomeric
      receptor ligands. Chimera peptides containing long spacers may prove to be useful
      tools for studying ORL1 receptor/mu-opioid receptor heterodimers.

PMID- 16814542
TI  - Synthesis and structure-activity relationships of retro bis-aminopyrrolidine urea
      (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone
      receptor-1 (MCH-R1). Part 1.
AB  - The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas
      are described. Compounds from this series exhibited potent binding affinity and
      functional activity at MCH-R1, and good oral bioavailability in rat.

PMID- 16814544
TI  - Correlation of antibacterial activity of some N-[5-(2-furanyl)-2-methyl-4-oxo-4H
      thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted-5-(2-furanyl)-2-methyl
      3H-thieno[2,3-d]pyrimidin-4-ones with topological indices using Hansch analysis.
AB  - The antimicrobial activity of the N-[5-(2-furanyl)-2-methyl-4-oxo-4H-theino[2,3
      d]pyrimidin-3-y1]-carboxamides and 3-substituted-5-(2-furanyl)-2-methyl-3H
      thieno[2,3-d]pyrimidin-4-ones was correlated with different topological indices
      using Hansch analysis. Good correlations were obtained through a simple
      regression equation with third order molecular connectivity index (3chi). The
      developed QSAR models were crossvalidated by leave-one-out technique.

PMID- 16814545
TI  - Discovery of a novel series of inhibitors of human cytomegalovirus primase.
AB  - Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible
      people throughout the world. We have discovered a series of imidazolyl-pyrimidine
      compounds, which were found to be irreversible inhibitors of the hCMV UL70
      primase based on results from radiolabeling and SAR studies. Two promising
      analogs are described that rival ganciclovir and cidofovir in antiviral potency
      and possess improved cytotoxicity profiles.

PMID- 16814547
TI  - Small molecule inhibitors of IgE synthesis.
AB  - A novel series of small molecule inhibitors of IgE synthesis are described.
      Compounds were optimized for potency, metabolic stability and absence of genetic
      toxicology.

PMID- 16814546
TI  - Selective COX-2 inhibitors. Part 1: synthesis and biological evaluation of
      phenylazobenzenesulfonamides.
AB  - A series of phenylazobenzenesulfonamide derivatives were designed and synthesized
      for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular
      assay using human whole blood (HWB) and an enzymatic assay using purified ovine
      enzymes. Extensive structure-activity relationships (SAR) were studied within
      this series, and several of selective COX-2 inhibitors have been identified.
      Among them, compound 8, 4-(4-amino-2-methylsulfanyl-phenylazo)benzenesulfonamide,
      showed a potent inhibitory activity to the cyclooxygenase enzymes (IC(50)'s for
      COX-1: 23.28 microM; COX-2: 2.04 microM), being active but less COX-2 selective
      than celecoxib.

PMID- 16814548
TI  - The effect of gait speed and gender on perceived exertion, muscle activity, joint
      motion of lower extremity, ground reaction force and heart rate during normal
      walking.
AB  - This study aims to investigate the effect of speed and gender on subjective
      perceived exertion, muscle activity, joint motion of lower extremity, vertical
      ground reaction force and heart rate during barefoot walking. Thirty healthy
      young adults, 15 females and 15 males, participated in this study. The Borg CR-10
      scale was applied to evaluate the perceived exertion of whole body and 10 local
      areas. Objective measurements included electromyography (EMG), joint motion,
      vertical ground reaction force (VGRF) and heart rate. The results indicate that
      walking speed had significant influence on perceived exertion of whole body, as
      well as the buttock, rear thigh, front thigh and rear shank areas (p<0.05).
      Increased walking speed caused significant increase in the muscle activities of
      lumbar erector spinae, biceps femoris, and medial gastrocnemius, lumbar motion,
      as well as the vertical ground reaction force in the loading response and mid
      stance phases. For gender effect, females showed significantly higher tibialis
      anterior muscle activity, ankle motion, vertical ground reaction force and
      average heart rate than males. Some systematic relations among the physiological,
      kinematics, kinetics and psychophysical responses were found for interpreting
      gait performance.

PMID- 16814549
TI  - Motor cortex reorganisation in Parkinson's disease.
AB  - Transcranial magnetic stimulation mapping of the motor cortical projection to the
      hand was performed in a group of patients with Parkinson's disease (PD) of
      variable duration to determine whether there is evidence of cortical
      reorganisation. Map shifts were found in the majority of PD cases (12/15), in
      untreated early cases as well as treated cases of longer duration, and there was
      a correlation between inter-side difference in the severity of PD symptoms
      (Unified Parkinson's Disease Rating Scale) and interhemispheric map displacement
      (r=0.60; P=0.018). These findings indicate that there is reorganisation of the
      corticomotor representation of the hand in PD, even at a relatively early stage
      of the disease, and suggest a dynamic process of reorganisation in the motor
      cortex due to an increase in the pallidal inhibitory inputs to the thalamo
      cortical projections.

PMID- 16814550
TI  - Rituximab therapy in chronic inflammatory demyelinating polyradiculoneuropathy
      with anti-SGPG IgM antibody.
AB  - We report a patient with chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) who showed high titers of anti-sulfated glucuronyl
      paragloboside (SGPG) IgM antibody without M-protein in serum. The patient was
      resistant to corticosteroids and immunosuppressants, but after administration of
      rituximab, clinical symptoms improved and the patient remained in a stable state
      for approximately 10 months. Rituximab may be a potent therapeutic option for
      refractory cases of CIDP irrespective of detectable M-protein in either serum or
      urine.

PMID- 16814551
TI  - Calvarial tuberculosis as the initial presentation of AIDS.
AB  - A rare case of a young immunocompromised patient with calvarial tuberculosis as
      the first symptom of human immunodeficiency virus-1 positivity is presented and
      the pertinent literature is reviewed.

PMID- 16814552
TI  - Double-layered lateral meniscus. A rare anatomical aberration.
AB  - We report a case of double-layered lateral meniscus, where an accessory proximal
      hemimeniscus was overlying the body and posterior horn of the lateral meniscus.
      It lay 1-2 mm proximal and parallel to the normal lateral meniscus with its
      periphery attached to the capsule and was significantly thinner and more mobile
      than its underlying counterpart. The accessory hemimeniscus was resected
      arthroscopically. This case demonstrates an interesting and extremely rare
      anatomical abnormality of the lateral meniscus and is the first one described
      outside a Japanese population.

PMID- 16814553
TI  - Calibration of cylindrical detectors using a simplified theoretical approach.
AB  - The calibration of cylindrical detectors using different types of radioactive
      sources is a matter of routine. The most accurate method, that of experiment, is
      limited by several factors when the energy interval is broad, requiring a
      relatively large number of primary standards, implying considerable investment of
      money and time. Several other techniques can be used instead, including Monte
      Carlo simulations and semi-empirical methods. Calculations based on the first
      technique require good definition of the geometry and materials, including the
      dead layer and window thickness together with an accurate set of cross-sections.
      The second technique requires two different types of experimental input, the
      first being from use of sources emitting cascade gamma rays and the second from
      use of sources emitting isolated gamma rays in order to cover the wide energy
      range and provide coincidence-summing corrections, respectively. Here, we
      introduce a new theoretical approach based on the Direct Statistical method
      proposed by Selim and Abbas to calculate the total and the full-energy peak
      (photopeak) efficiencies for both point and thin circular disk sources for
      scintillation and semiconductor detectors. The present method combines
      calculation of the average path length covered by the photon inside the detector
      active volume and the geometrical solid angle Omega, to obtain a simple formula
      for the different efficiencies. Results from the present model were tested
      against data sets obtained with previous treatments in order to underline how
      simple and fast our calculations are.

PMID- 16814554
TI  - Ranges of 40 keV ions in polycrystalline tungsten and gold.
AB  - Integral range profiles for various 40keV radioactive ions from (7)Be to (204)Tl
      were measured in tungsten and gold using sectioning techniques based on anodizing
      and stripping. Measured range distributions exhibited long tails extending into
      the metals. Median range values for a given ion were the same in tungsten as in
      gold, but were about 1.7 times greater than calculations of projected ranges
      based on the SRIM computer code.

PMID- 16814555
TI  - Increased proliferation reflects glial and vascular-associated changes, but not
      neurogenesis in the presenile Alzheimer hippocampus.
AB  - Adult proliferation and hippocampal neurogenesis are stimulated by injury. In
      agreement, aberrant cell-cycle-related protein expression has been reported in
      senile Alzheimer's disease (AD), where the hippocampus is particularly affected.
      Recently, increased expression of doublecortin (DCX), a neurogenesis marker, was
      reported in senile AD. Here, we addressed whether proliferative and neurogenic
      responses also occur in younger, i.e., presenile AD cases, using
      immunohistochemistry for Ki-67, GFAP and DCX. Increased numbers of Ki-67+ cells
      with a healthy, non-mature appearance were found in CA1-3. These were mainly due
      to glial and vasculature-associated changes, while DCX immunostaining appeared
      sensitive to postmortem breakdown. We found no indications for altered dentate
      gyrus neurogenesis. Our data obtained using validated methodology in a well
      characterized, presenile cohort thus differ from previous data obtained in senile
      AD. They reflect clear differences in proliferative responsivity, particularly in
      the glia and vascular components, and suggest different underlying mechanisms in
      these groups.

PMID- 16814556
TI  - Extraction and partial characterization of polyphenol oxidase from banana (Musa
      acuminata Grande naine) roots.
AB  - Polyphenol oxidase activity (PPO, EC 1.14.18.1, monophenol monooxygenase, and EC
      1.10.3.2, o-diphenoloxidase) has been extensively studied in banana fruit for its
      role in enzymatic browning. Rapid discolouration of leaf, stem and root tissue
      after injury and strong pigmentation of tissue extracts indicate that PPO and
      phenolic compounds are ubiquitous in vegetative tissue of banana as well. They
      hamper biochemical and molecular studies in banana, as cumbersome adaptations of
      extraction protocols are required. On the other hand, PPO and phenolic compounds
      could be an important part of the plant's defence system against pests and
      diseases, including root parasitic nematodes. To facilitate future studies in
      this area, extraction and assay conditions for PPO from roots of banana (Musa
      acuminata AAA, Grande naine) were optimized. Highest enzyme activities were
      obtained in a 0.2 M phosphate buffer at pH 7.0 with 5% insoluble
      polyvinylpyrrolidone and 0.25% Triton X-100. The lowest K(m) values were obtained
      for dopamine and D-catechin. Monophenolase activity was shown with p-cresol.
      Banana root PPO was strongly inhibited by dithiothreitol and sodium
      metabisulfite. In root sections, oxidation of dopamine strongly co-localized with
      aerenchyma in the cortex. The experiments revealed indications for the
      involvement of root PPO and dopamine in resistance of banana against the
      parasitic nematode Radopholus similis.

PMID- 16814557
TI  - High light intensity protects photosynthetic apparatus of pea plants against
      exposure to lead.
AB  - The electron transport rates and coupling factor activity in the chloroplasts;
      adenylate contents, rates of photosynthesis and respiration in the leaves as well
      as activity of isolated mitochondria were investigated in Pisum sativum L. leaves
      of plants grown under low or high light intensity and exposed after detachment to
      5 mM Pb(NO(3))(2). The presence of Pb(2+) reduced rate of photosynthesis in the
      leaves from plants grown under the high light (HL) and low light (LL) conditions,
      whereas the respiration was enhanced in the leaves from HL plants. Mitochondria
      from Pb(2+) treated HL-leaves oxidized glycine at a higher rate than those
      isolated from LL leaves. ATP content in the Pb-treated leaves increased to a
      greater extend in the HL than LL grown plants. Similarly ATP synthase activity
      increased markedly when chloroplasts isolated from control and Pb-treated leaves
      of HL and LL grown plants were subjected to high intensity light. The presence of
      Pb ions was found inhibit ATP synthase activity only in chloroplasts from LL
      grown plants or those illuminated with low intensity light. Low light intensity
      during growth also lowered PSI electron transport rates and the Pb(2+) induced
      changes in photochemical activity of this photosystem were visible only in the
      chloroplasts isolated from LL grown plants. The activity of PSII was influenced
      by Pb ions on similar manner in both light conditions. This study demonstrates
      that leaves from plants grown under HL conditions were more resistant to lead
      toxicity than those obtained from the LL grown plants. The data indicate that
      light conditions during growth might play a role in regulation of photosynthetic
      and respiratory energy conservation in heavy metal stressed plants by increasing
      the flexibility of the stoichiometry of ATP to ADP production.

PMID- 16814558
TI  - Molecular characterization of a potato MAP kinase transcriptionally regulated by
      multiple environmental stresses.
AB  - The MAPK cascade is an evolutionary conserved signaling pathway that links
      external stimuli with cellular responses. Using polymerase chain reaction (PCR),
      a DNA fragment corresponding to a Solanum tuberosum MAPK, StMPK1, was isolated.
      StMPK1 amino acid sequence displayed over 90% identity with tomato MPK1 (LeMPK1)
      and tobacco SIPK. Southern blot analysis indicated that the gene encoding StMPK1
      is present in a single copy in the potato genome. StMPK1 mRNA levels
      differentially accumulated in potato tuber in response to wounding and to
      wounding plus Fusarium solani f. sp. eumartii. Transcript accumulation after
      infection was transient and started earlier than what was observed in wounded
      tubers. StMPK1 mRNA levels also increased in potato tuber after 24 h of treatment
      with jasmonic acid (JA) and abscicic acid (ABA), but not in response to ethylene
      or salicylic acid. In addition, StMPK1 transcript levels increased after a heat
      shock treatment at 42 degrees C. The results suggest that StMPK1 may participate
      in the cellular responses against multiple environmental stimuli in potato
      tubers.

PMID- 16814559
TI  - Mechanisms of interleukin-6 protection against ischemia-reperfusion injury in rat
      liver.
AB  - Numerous animal studies simulating liver injury have demonstrated that
      interleukin-6 (IL-6) exerts a protective effect. This study was designed to
      further analyze the molecular mechanisms underlying the protective role of IL-6
      in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at
      high doses reduces cell damage which occurs in ischemic-reperfused liver, while
      at low doses displays only a limited protective capacity, (ii) anticipates and
      enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver
      also at a low, more pharmacologically acceptable dose, (iii) sustains the acute
      phase response which is dampened in ischemic-reperfused liver, (iv) strengthens
      the heat shock-stress response shown by ischemic-reperfused liver and (v)
      overcomes the dysfunctions of the unfolding protein response found in ischemic
      reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays
      a crucial role in the potentiation of the different protective pathways activated
      in ischemic-reperfused liver. Our data confirm that IL-6 is a potential
      therapeutic in liver injury of different etiologies and reveal novel mechanisms
      by which IL-6 sustains liver function after ischemia/reperfusion injury.

PMID- 16814560
TI  - The pharmacoeconomic impact of amlodipine use on coronary artery disease.
AB  - The most frequent cause of mortality and morbidity in industrialized countries is
      coronary artery disease (CAD), which in Europe alone is responsible for around
      two million deaths per year. In 2001 it accounted for about 260,000 hospital
      discharges in Italy. The costs of CAD treatment in Italy--which were borne by the
      Italian state, the third-party payer--amounted to 800 million euros. We propose
      to assess the pharmacoeconomic implications of using amlodipine besylate
      treatment in Italy for patients with coronary artery disease. The study is based
      on a post-hoc cost-effectiveness analysis that compared standard care
      supplemented by amlodipine besylate with ordinary standard care over a 36-month
      time horizon. The clinical outcome data were based on the prospective randomized
      evaluation of vascular effect of norvasc trial (PREVENT). Direct medical costs
      referred to the purchase costs of amlodipine besylate and the cost of National
      Health Service (NHS) hospitalization. The costs were discounted back at an annual
      rate of 5%. Patients administered amlodipine besylate exhibited a significant
      risk reduction with respect to any major vascular event or procedure when
      compared to the placebo group. The reduction mainly referred to unstable angina
      events and revascularization procedures. We estimated that the total cost of
      adding amlodipine besylate to standard care amounted to 139,050 euros per 1000
      patients treated for 36 months. This represents a cost of 1780 euros per patient
      remaining free of any vascular event. Results were sensitive to both clinical and
      economic variables. The incremental costs of the alternative therapy ranged from
      296 euros to 5066 per patient free of any event in, respectively, the best and
      worst scenario. Amlodipine besylate therapy can be a cost-effective strategy for
      CAD treatment in Italy. Our economic evaluation demonstrated, first, that by
      reducing vascular events and the need for revascularization procedures savings
      were achieved in hospital expenditure, and, second, that such savings could
      significantly offset drug costs.

PMID- 16814561
TI  - Flow injection on-line solid phase extraction coupled with inductively coupled
      plasma mass spectrometry for determination of (ultra)trace rare earth elements in
      environmental materials using maleic acid grafted polytetrafluoroethylene fibers
      as sorbent.
AB  - A new sorbent, maleic acid grafted polytetrafluoroethylene fiber (MA-PTFE), was
      prepared and evaluated for on-line solid-phase extraction coupled with
      inductively coupled plasma mass spectrometry (ICP-MS) for fast, selective, and
      sensitive determination of (ultra)trace rare earth elements (REEs) in
      environmental samples. The REEs in aqueous samples at pH = 3.0 were selectively
      extracted onto a microcolumn packed with the MA-PTFE fiber, and the adsorbed REEs
      were subsequently eluted on-line with 0.9 mol l(-1) HNO3 for ICP-MS
      determination. The new sorbent extraction system allows effective
      preconcentration and separation of the REEs from the major matrix constituents of
      alkali and alkali earth elements, particularly their separation from barium that
      produces considerable isobaric interferences of 134Ba16O1H+, 135Ba16O+,
      136Ba16O1H+, and 137Ba16O+ on 151Eu+ and 153Eu+. With the use of a sample loading
      flow rate of 7.4 ml min(-1) for 120 s preconcentration, enhancement factors of 69
      97 and detection limits (3s) of 1-20 pg l(-1) were achieved at a sample
      throughput of 22 samples h(-1). The precision (RSD) for 16 replicate
      determinations of 50 ng l(-1) of REEs was 0.5-1.1%. The developed method was
      successfully applied to the determination of (ultra)trace REEs in sediment, soil,
      and seawater samples.

PMID- 16814562
TI  - Stem cell enrichment approaches.
AB  - Adult somatic tissue, and the tumours that arise therein, are maintained by a
      small population of stem cells. In addition to the self-renewal potential and
      pluripotency, these stem cells express several phenotypic traits that can be used
      in isolation and enrichment strategies. Since most of the traits are not
      exclusive to the stem cells however, the resultant populations are typically
      heterogeneous and variable from one isolation to another. In this article, we
      review the strategies for isolation of stem cells, and the limitations thereof,
      with emphasis on mesenchymal tissue and bone tumours. The emerging evidence
      suggests that stem cell is not a distinct entity, but rather an indefinite state
      along a spectrum, characterized by phenotypic traits, epigenetic factors and the
      microenvironment.

PMID- 16814563
TI  - Transposon-mediated gene trapping in zebrafish.
AB  - The Tol2 transposon system can create chromosomal insertions in the zebrafish
      germ lineage very efficiently. We constructed a Tol2-based gene trap vector,
      T2KSAG, which contains a splice accepter, the GFP gene and the polyA signal. In
      the pilot screen for gene trapping using T2KSAG, we identified 38 fish lines
      expressing GFP in specific organs and tissues. In the SAGp53A line, GFP is
      expressed in the forebrain and midbrain, and the insertion of the gene trap
      construct captured a transcript of the kab gene encoding a zebrafish homolog of
      the human KARP (Ku86 autoantigen related protein)-binding protein (KAB). In the
      SAGm18B line, GFP is expressed in the central nervous system, and the insertion
      captured a transcript of a gene for succinyl CoA:3-oxoacid CoA-transferase
      (SCOT). Here, we describe how we performed the gene trap screen and characterized
      the gene trap insertions and will discuss the outcome of the pilot screen.

PMID- 16814564
TI  - Expression and purification of dalcochinase, a beta-glucosidase from Dalbergia
      cochinchinensis Pierre, in yeast and bacterial hosts.
AB  - The coding sequence of the mature dalcochinase, a beta-glucosidase from Dalbergia
      cochinchinensis Pierre, was cloned and expressed in various systems. Expression
      in Escherichia coli resulted in an insoluble protein, which could be made soluble
      by co-expression with bacterial chaperonin GroESL. However, the enzyme had no
      activity. Recombinant expression in Pichia pastoris and Saccharomyces cerevisiae
      yielded an active enzyme. Dalcochinase was expressed under methanol induction in
      P. pastoris, since this was much more efficient than constitutive expression in
      P. pastoris or in S. cerevisiae. Addition of 0.5% casamino acids to the culture
      medium stabilized the pH of the culture and increased the protein yield by 3- to
      5-folds. Insertion of a polyhistidine-tag either after the N-terminal alpha
      factor signal sequence or at the C-terminus failed to assist in purification by
      immobilized metal-ion affinity chromatography (IMAC) due to post-translational
      processing at both termini. A new construct of dalcochinase with an N-terminal
      truncation following the propeptide and eight histidine residues enabled its
      purification by IMAC, following hydrophobic interaction chromatography. The
      purified recombinant dalcochinase was apparently composed of differently post
      translationally modified forms, but had kinetic properties and pH and temperature
      optima comparable to natural dalcochinase. The procedures reported here overcome
      the limitation in enzyme supply from natural sources, and allow further studies
      on structure-function relationships in this enzyme.

PMID- 16814565
TI  - Expression and purification of His-tagged HPV16 E7 protein active in pRb binding.
AB  - Human papillomavirus type 16 (HPV16) protein E7 is the major oncogenic factor
      associated with the development of human cervical cancer. The transforming
      activity of the E7 protein is linked to its interaction with host regulatory
      proteins such as the retinoblastoma tumor suppressor protein. The recombinant
      production of E7 protein is a prerequisite for its structural and functional
      characterization as well as for the development of various preventive and
      therapeutic strategies. We present an approach to enhance the soluble expression
      of His-tagged E7 protein by optimization of the E7 gene and the expression
      conditions in the host Escherichia coli. We also report a detailed protocol for
      the purification of E7 protein by standard chromatographic methods. The binding
      of E7 protein to the recombinant non-phosphorylated form of retinoblastoma
      protein was examined by ELISA and surface plasmon resonance analysis. These
      studies confirm that the recombinant His-tagged E7 protein retains its
      conformational properties and biological activity.

PMID- 16814566
TI  - Physico-chemical and biological characterizations of two human prolactin analogs
      exhibiting controversial bioactivity, synthesized in Chinese hamster ovary (CHO)
      cells.
AB  - The synthesis, purification and characterization of G129R-hPRL and S179D-hPRL,
      the two better-studied antagonists of human prolactin (hPRL), is described. Both
      of these have been expressed for the first time, in their authentic form, by a
      stable CHO cell line, at secretion levels of 7.7 and 4.3 microg/10(6) cells/day,
      respectively. Previous studies had shown that these hPRL analogs, when produced
      in bacterial cytoplasm, consistently contained misfolded forms and multimers
      according to the specific denaturation, refolding and purification conditions.
      These versions also have an N-terminal extra methionine. An extensive physico
      chemical characterization was carried out after a practical two-step purification
      process and included SDS-PAGE and Western blotting analysis, matrix-assisted
      laser-desorption ionization time-of-flight mass spectral (MALDI-TOF-MS) analysis,
      high-performance size-exclusion chromatography (HPSEC) and reversed-phase high
      performance liquid chromatography (RP-HPLC). This last technique revealed a
      considerable difference in hydrophobicity due to a single amino acid
      substitution, with S179D-hPRL less (t(RR) = 0.85 +/- 0.010) and G129R-hPRL more
      (t(RR) = 1.10 +/- 0.013) hydrophobic than hPRL, where t(RR) is the relative
      retention time. The biological characterization was based on further refinement
      of a sensitive proliferation assay using the pro-B murine cell line (Ba/F3)
      transfected with the long form hPRL receptor cDNA such that the minimal
      detectable dose was 0.04 ng of hPRL/mL, the Ba/F3-LLP assay. On the basis of this
      assay, the relative residual agonistic activity of these two products, determined
      against a hPRL international standard in four independent assays, was 53 x 10(-3)
      for S179D-hPRL and 70 x 10(-5) for G129R-hPRL. We believe that the present
      synthesis and characterization could be extremely helpful for studies of these
      two proteins, which have been reported to antagonize tumor growth-promoting
      effects of hPRL in vivo in animal models of breast and prostate cancer.

PMID- 16814567
TI  - Magnetic resonance imaging of the migration of neuronal precursors generated in
      the adult rodent brain.
AB  - Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in
      rodents. These NPCs give rise to neural precursors in adults that migrate to the
      olfactory bulb (OB) along a well-defined pathway, the rostral migratory stream
      (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats
      with fluorescent, micron-sized iron oxide particles (MPIOs), and that magnetic
      resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs
      along the RMS to the OB. Immunohistochemistry and electron microscopy indicated
      that particles were inside GFAP(+) neural progenitor cells in the SVZ, migrating
      PSA-NCAM(+) and Doublecortin(+) neural precursors within the RMS and OB, and Neu
      N(+) mature neurons in the OB. This work demonstrates that in vivo cell labeling
      of progenitor cells for MRI is possible and enables the serial, non-invasive
      visualization of endogenous progenitor/precursor cell migration.

PMID- 16814568
TI  - Oscillatory correlates of the primacy effect in episodic memory.
AB  - Both intracranial and scalp EEG studies have demonstrated that oscillatory
      activity, especially in the gamma band (28 to 100 Hz), can differentiate
      successful and unsuccessful episodic encoding [Sederberg, P.B., Kahana, M.J.,
      Howard, M.W., Donner, E.J., Madsen, J.R., 2003. Theta and gamma oscillations
      during encoding predict subsequent recall. Journal of Neuroscience, 23(34), 10809
      10814; Fell, J., Klaver, P., Lehnertz, K., Grunwald, T., Schaller, C., Elger,
      C.E., Fernandez, G., 2001. Human memory formation is accompanied by rhinal
      hippocampal coupling and decoupling. Nature Neuroscience, 4 (12), 1259-1264;
      Gruber, T., Tsivilis, D., Montaldi, D., and Muller, M. (2004). Induced gamma band
      responses: An early marker of memory encoding and retrieval. Neuroreport, 15,
      1837-1841; Summerfield, C., Mangels, J.A., in press. Dissociable neural
      mechanisms for encoding predictable and unpredictable events. Journal of
      Cognitive Neuroscience]. Although the probability of recalling an item varies as
      a function of where it appeared in the list, the relation between the oscillatory
      dynamics of successful encoding and serial position remains unexplored. We
      recorded scalp EEG as participants studied lists of common nouns in a delayed
      free-recall task. Because early list items were recalled better than items from
      later serial positions (the primacy effect), we analyzed encoding-related changes
      in 2 to 100 Hz oscillatory power as a function of serial position. Increases in
      gamma power in posterior regions predicted successful encoding at early serial
      positions; widespread low-frequency (4-14 Hz) power decreases predicted
      successful memory formation for later serial positions. These results suggest
      that items in early serial positions receive an encoding boost due to focused
      encoding without having to divide resources among numerous list items. Later in
      the list, as memory load increases, encoding is divided between multiple items.

PMID- 16814569
TI  - Phylogeography of the Calonectris shearwaters using molecular and morphometric
      data.
AB  - We investigated phylogenetic relationships and the biogeographic history of the
      Calonectris species complex, using both molecular and biometric data from one
      population of the Cape Verde shearwater Calonectris edwardsii (Cape Verde
      Islands), one from the streaked shearwater C. leucomelas (western Pacific Ocean)
      and 26 from Cory's shearwater populations distributed across the Atlantic (C. d.
      borealis) and the Mediterranean (C. d. diomedea). The streaked shearwater
      appeared as the most basal and distant clades, whereas the genetic divergences
      among the three main clades within the Palearctic were similar. Clock
      calibrations match the first speciation event within Calonectris to the Panama
      Isthmus formation, suggesting a vicariant scenario for the divergence of the
      Pacific and the Palearctic clades. The separation between the Atlantic and
      Mediterranean clades would have occurred in allopatry by range contraction
      followed by local adaptation during the major biogeographic events of the
      Pleistocene. The endemic form from Cape Verde probably evolved as a result of
      ecological divergence from the Mediterranean subspecies. Finally, one
      Mediterranean population (Almeria) was unexpectedly grouped into the Atlantic
      subspecies clade, both by genetic and by morphometric analyses, pointing out the
      Almeria-Oran oceanographic front (AOOF) as the actual divide between the two
      Cory's shearwater subspecies. Our results highlight the importance of
      oceanographic boundaries as potentially effective barriers shaping population and
      species phylogeographical structure in pelagic seabirds.

PMID- 16814570
TI  - Molecular phylogeny of the Arctoidea (Carnivora): effect of missing data on
      supertree and supermatrix analyses of multiple gene data sets.
AB  - Phylogenetic relationships of 79 caniform carnivores were addressed based on four
      nuclear sequence-tagged sites (STS) and one nuclear exon, IRBP, using both
      supertree and supermatrix analyses. We recovered the three major arctoid
      lineages, Ursidae, Pinnipedia, and Musteloidea, as monophyletic, with Ursidae
      (bears) strongly supported as the basal arctoid lineage. Within Pinnipedia,
      Phocidae (true seals) were sister to the Otaroidea [Otariidae (fur seals and sea
      lions) and Odobenidae (walrus)]. Phocid subfamily and tribal designations were
      supported, but the otariid subfamily split between fur seals and sea lions was
      not. All family designations within Musteloidea were strongly supported:
      Mephitidae (skunks), Ailuridae (monotypic red panda), Mustelidae (weasels,
      badgers, otters), and Procyonidae (raccoons). A novel hypothesis for the position
      of the red panda was recovered, placing it as branching after Mephitidae and
      before Mustelidae+Procyonidae. Within Mustelidae, subfamily taxonomic changes are
      considered. This study represents the most comprehensive sampling to date of the
      Caniformia in a molecular study and contains the most complete molecular
      phylogeny for the Procyonidae. Our data set was also used in an empirical
      examination of the effect of missing data on both supertree and supermatrix
      analyses. Sequence for all genes in all taxa could not be obtained, so two
      variants of the data set with differing amounts of missing data were examined.
      The amount of missing data did not have a strong effect; instead, phylogenetic
      resolution was more dependent on the presence of sufficient informative
      characters. Supertree and supermatrix methods performed equivalently with
      incomplete data and were highly congruent; conflicts arose only in weakly
      supported areas, indicating that more informative characters are required to
      confidently resolve close species relationships.

PMID- 16814571
TI  - Molecular phylogenetic relationships of Xiphidiopicus percussus, Melanerpes, and
      Sphyrapicus (Aves: Picidae) based on cytochrome B sequence.
AB  - The endemic woodpecker, Xiphidiopicus percussus, from Cuba has been postulated as
      the sister taxon to the Hispaniolan woodpecker (Melanerpes striatus) and its
      relationships to the genera Sphyrapicus and Melanerpes have been speculated. We
      used mitochondrial cytochrome b sequences from a collection of New World picids
      to investigate the phylogenetic relationships among these species using maximum
      parsimony and maximum likelihood approaches. Our data suggest that X. percussus
      is the sister taxon to the Melanerpes woodpeckers, which appear to group into a
      single distinct clade. Xiphidiopicus percussus is not the sister taxon to M.
      striatus as has been postulated [Olson, S., 1972. The generic distinction of the
      Hispaniolan Woodpecker, Chryserpes striatus (Aves: Picidae). Proc. Biol. Soc.
      Wash. 85, 499-508]. The genus Sphyrapicus appears to have diverged earlier than
      Xiphidiopicus. Divergence estimates from the cytochrome b sequences indicate that
      Xiphidiopicus probably diverged sometime in the late Miocene-early Pliocene, and
      the endemic contemporary species X. percussus on Cuba may be a relict from a
      group that originated in Central America or North America.

PMID- 16814572
TI  - Origin of the tetraspanin uroplakins and their co-evolution with associated
      proteins: implications for uroplakin structure and function.
AB  - Genome level information coupled with phylogenetic analysis of specific genes and
      gene families allow for a better understanding of the structure and function of
      their protein products. In this study, we examine the mammalian uroplakins (UPs)
      Ia and Ib, members of the tetraspanin superfamily, that interact with uroplakins
      UPII and UPIIIa/IIIb, respectively, using a phylogenetic approach of these genes
      from whole genome sequences. These proteins interact to form urothelial plaques
      that play a central role in the permeability barrier function of the apical
      urothelial surface of the urinary bladder. Since these plaques are found
      exclusively in mammalian urothelium, it is enigmatic that UP-like genomic
      sequences were recently found in lower vertebrates without a typical urothelium.
      We have cloned full-length UP-related cDNAs from frog (Xenopus laevis), chicken
      (Gallus gallus), and zebrafish (Danio rerio), and combined these data with
      sequence information from their orthologs in all the available fully sequenced
      and annotated animal genomes. Phylogenetic analyses of all the available
      uroplakin sequences, and an understanding of their distribution in several animal
      taxa, suggest that: (i) the UPIa/UPIb and UPII/UPIII genes evolved by gene
      duplication in the common ancestor of vertebrates; (ii) uroplakins can be lost in
      different combinations in vertebrate lineages; and (iii) there is a strong co
      evolutionary relationship between UPIa and UPIb and their partners UPII and
      UPIIIa/IIIb, respectively. The co-evolution of the tetraspanin UPs and their
      associated proteins may fine-tune the structure and function of uroplakin
      complexes enabling them to perform diverse species- and tissue-specific
      functions. The structure and function of uroplakins, which are also expressed in
      Xenopus kidney, oocytes and fat body, are much more versatile than hitherto
      appreciated.

PMID- 16814573
TI  - Sicyopterus "lagocephalus", a unique widespread taxon confirmed by mtDNA
      sequences.

PMID- 16814574
TI  - The RAG-1 exon in the avian order Caprimulgiformes: phylogeny, heterozygosity,
      and base composition.
AB  - We sequenced 2.8 kb of the RAG-1 exon for most of the extant genera in the avian
      order Caprimulgiformes to investigate monophyly of the order and phylogeny within
      the traditional families. The order is not monophyletic: the Aegothelidae (owlet
      nightjars) were the sister group of the Apodiformes (swifts and hummingbirds).
      There was no support for the monophyly of a clade containing the remaining
      families of Caprimulgiformes. However, the RAG-1 data strongly supported a
      relationship between the Podargidae (frogmouths) and Caprimulgidae (nightjars).
      Within the Caprimulgidae, the Australasian genus Eurostopodus was sister to the
      rest of the family, which in turn was composed of four major clades, three of
      which were restricted to the New World and primarily to the Neotropics. The Old
      World caprimulgids form a monophyletic clade embedded within the New World taxa;
      consequently, most Old World nightjars are probably the result of a single
      expansion out of the Neotropics. The genus Caprimulgus was not found to be
      monophyletic. Several species in the Caprimulgidae have both elevated
      heterozygosity and high GC3 content; it is likely that these are causally
      related.

PMID- 16814575
TI  - Cross-cultural adaptation and validation of Singapore English and Chinese
      versions of the Knee injury and Osteoarthritis Outcome Score (KOOS) in Asians
      with knee osteoarthritis in Singapore.
AB  - OBJECTIVE: To cross-culturally adapt and validate Singapore English and Chinese
      versions of the Knee injury and Osteoarthritis Outcome Score (KOOS) in patients
      with knee osteoarthritis (OA) in Singapore. METHODS: Singapore English and
      Chinese versions were cross-culturally adapted from the source English KOOS
      following standard guidelines (including cognitive debriefing). Patients were
      asked to complete identical questionnaires containing the KOOS, Short Form 36
      Health Survey, and EQ-5D twice within 6 days. Reliability was assessed using
      Cronbach's alpha and intraclass correlation coefficients (ICC), dimensionality
      using item-to-domain correlations and convergent and divergent construct validity
      using 14 and 13 a priori hypotheses, respectively. RESULTS: Singapore English and
      Chinese KOOS versions were well accepted by patients in pilot testing and were
      therefore administered to a consecutive sample of 127 English and 131 Chinese
      speaking Singaporeans with knee OA. Cronbach's alpha exceeded 0.7 for all domains
      except for Chinese pain and symptoms domains. ICC exceeded 0.7 for all domains
      except for English sport and recreation and Chinese knee-related QoL domains.
      Hypothesized item-to-domain correlations (Spearman's rho>or=0.4) were observed
      for 38 items in English and 29 in Chinese versions. Convergent construct validity
      was supported by the presence of hypothesized moderate/strong correlations
      (rho=0.37-0.65) for 13 and 11 a priori hypotheses in the English and Chinese
      KOOS, respectively. Divergent construct validity was supported by the presence of
      weak correlations (rho=0.02-0.34) for 12 and 11 a priori hypotheses in the
      English and Chinese KOOS, respectively. CONCLUSION: The Singapore English and
      Chinese KOOS were well accepted and demonstrated acceptable reliability and
      validity in Asian patients with knee OA in Singapore.

PMID- 16814576
TI  - Involvement of muscarinic acetylcholine receptors in chloride secretion by
      cultured rat epididymal epithelium.
AB  - The aim of our present study was to investigate the short-circuit current
      response to carbachol in cultured rat cauda epididymal epithelia and the signal
      transduction mechanisms involved. Carbachol added basolaterally induced a
      concentration-dependent increase in short-circuit current (Isc) across the
      epididymal epithelium consisting of a rapidly rising phase and a long term
      sustained response. The response was almost abolished by removing Cl(-) from the
      extracellular medium and blockable by pretreating the tissues with DPC,
      indicating a substantial contribution of Cl(-) secretion to the carbachol-induced
      response. The muscarinic acetylcholine receptor antagonist atropine inhibited the
      response, but the nicotinic acetylcholine receptors antagonist curarine had no
      effect, suggesting that only the muscarinic acetylcholine receptors mediated the
      secretory response of the basolateral side of rat cauda epididymal epithelium to
      carbachol. Addition of carbachol to the apical side of the tissue was found not
      to elicit an Isc response. These results suggested that muscarinic receptors are
      present in the basolateral side of rat cauda epididymal epithelium. Activation of
      these receptors by acetylcholine released from the nerve endings regulates
      epididymal transepithelial Cl(-) secretion. Cholinergic stimulation therefore
      contributes to the formation of luminal fluid microenvironment.

PMID- 16814577
TI  - Stage-specific and differential notch dependency at the alphabeta and gammadelta
      T lineage bifurcation.
AB  - Signals transduced by Notch receptors are indispensable for T cell specification
      and differentiation of alphabeta T lineage cells. However, the role of Notch
      signals during alphabeta versus gammadelta T lineage decision remains
      controversial. Here, we addressed this question by employing a clonal analysis of
      CD4(-)CD8(-) (DN) progenitor potential to position the divergence of alphabeta
      and gammadelta T cell lineages to the late DN2 to DN3 developmental stages.
      Accordingly, alphabeta and gammadelta precursor frequencies within these T cell
      progenitor subsets were determined, both in the presence and absence of Notch
      signaling through Delta-like 1. Notch signals were found to be critical for the
      DN to CD4(+)CD8(+) (DP) transition, irrespective of the identity (pTalphabeta or
      gammadelta) of the inducing T cell receptor complex, whereas gammadelta T cells
      developed from gammadeltaTCR-expressing T cell progenitors in the absence of
      further Notch ligand interaction. Collectively, our findings demonstrate a
      differential, stage-specific requirement for Notch receptor-ligand interactions
      in the differentiation of alphabeta and gammadelta T cells from T cell
      progenitors.

PMID- 16814579
TI  - Effect of Cryphonectria hypovirus 1 (CHV1) infection on Cpkk1, a mitogen
      activated protein kinase kinase of the filamentous fungus Cryphonectria
      parasitica.
AB  - We screened Cryphonectria parasitica genomic and cDNA libraries with a probe
      obtained from the amplification of a conserved region among the sequence of known
      mitogen activated protein kinase kinases (MAPKK) and obtained genomic and cDNA
      clones. Sequence comparisons of the clones obtained confirmed the identification
      of a C. parasitica homologue to other fungal MAPKK, which we named Cpkk1.
      Polyclonal antibodies raised against a purified Cpkk1 fusion protein expressed in
      Escherichia coli were used to detect Cpkk1 protein in extracts of CHV1-infected
      and uninfected C. parasitica grown in liquid culture. Differences in the dynamics
      of phosphorylation and dephosphorylation were noticed. Under the conditions
      investigated, Cpkk1 protein expression is associated with active mycelial growth,
      before the onset of a senescent developmental stage. We hypothesize that
      differences in Cpkk1 phosphorylation state between CHV1 infected and virus free
      strains are due to a delay of the onset of the developmental stage caused by the
      presence of the virus.

PMID- 16814578
TI  - Partial correction of murine beta-thalassemia with a gammaretrovirus vector for
      human gamma-globin.
AB  - Several studies have demonstrated that recombinant lentivirus vectors containing
      extended globin gene expression cassettes and regulatory elements can ameliorate
      the pathogenic sequela in murine models of beta-thalassemia and sickle cell
      disease. Similarly promising results have not yet been obtained with recombinant
      gammaretrovirus vectors. Of these two vector classes, only gammaretroviruses have
      been tested extensively in clinical trials, with a proven ability to transduce
      long-term reconstituting hematopoietic stem cells with an exceedingly low
      incidence of serious side effects. Toward the continuing goal of developing
      retrovirus vectors for the treatment of the beta-chain hemoglobinopathies, we
      report here the assessment of a recombinant gammaretrovirus vector for human
      gamma-globin in murine models of beta-thalassemia. In the beta-thalassemia
      intermedia Hbbth-3/+ model, we observed a dose-dependent but transient increase
      in total hemoglobin and red blood cells, with a 2.5 +/- 0.2 g/dL increase in
      hemoglobin for transduction rates > or = 33%. In the severe beta-thalassemia
      major Hbbth-3/Hbbth-3 model, we observed a modest but statistically significant
      increase in survival, from a median of 15 days to 30 days (P = 0.001). These
      studies provide the first evidence that globin gene transfer vectors based on
      recombinant gammaretroviruses may provide a viable option for the treatment of
      the beta-chain hemoglobinopathies.

PMID- 16814580
TI  - Sample-specific diamagnetic and paramagnetic passive shimming.
AB  - When homogenizing the static magnetic field over extended in vivo volumes,
      significant residual inhomogeneity can remain after spherical harmonic shim
      optimization. This is due to the low spatial orders of shims available on in vivo
      MR systems and the presence of higher-order inhomogeneity in the vicinity of
      anatomic air cavities. Mediation of this problem through the development of
      higher-order spherical harmonic shims is severely impeded by bore space
      limitations. Sample-specific passive shims are not limited to low-order spatial
      compensation and offer an alternative means to increased homogenization. Here, we
      present a novel construction protocol for sample-specific passive shims comprised
      of both diamagnetic (bismuth) and paramagnetic (zirconium) materials. A prototype
      shim is constructed and shown to significantly homogenize the mouse brain at 9.4
      T. Further homogenization capabilities are simulated through alteration of the
      shim construction.

PMID- 16814581
TI  - Two-dimensional one pulse MAS of half-integer quadrupolar nuclei.
AB  - We show that the two-dimensional one pulse (TOP) representation of magic-angle
      spinning nuclear magnetic resonance data of half-integer quadrupolar nuclei has
      significant advantages over the conventional one-dimensional spectrum. The TOP
      spectrum, which correlates NMR frequency to spinning sideband order, provides a
      rapid determination of the number of sites as well as the size of the their
      quadrupolar coupling. Additionally, synchronous acquisition spectra of the
      central and satellite transition resonances can be separated by different
      projections of the TOP spectrum, with higher resolution spectra often found in
      the satellite transitions projection. A previously perceived problem of
      centerband aliasing in TOP can be eliminated with an algorithm that uses larger
      subspectral widths and the sideband order dimension to distinguish centerbands
      from sidebands.

PMID- 16814582
TI  - Development of a dual cell, flow-injection sample holder, and NMR probe for
      comparative ligand-binding studies.
AB  - NMR based ligand screening is becoming increasingly important for the very early
      stages of drug discovery. We have proposed a method that makes highly efficient
      use of a single sample of a scarce target, or one with poor or limited
      solubility, to screen an entire compound library. This comparative method is
      based on immobilizing the target for the screening procedure. In order to support
      the method, a dual cell, flow injection probe with a single receiver coil has
      been constructed. The flow injection probe has been mated to a single high
      performance pump and sample handling system to enable the automated analysis of
      large numbers of compound mixes for binding to the target. The probe, having an 8
      mm 1H/2H dual tuned coil and triple axis gradients, is easily shimmed and yields
      NMR spectra of comparable quality to a standard 5 mm high-resolution probe. The
      lineshape in the presence of a solid support is identical to that in glass NMR
      tubes in a 5 mm probe. Control spectra of each cell are identical and well
      separated, while ligand binding in a complex mixture can be readily detected in
      20-30 min, thus paving the way for use of the probe for actual drug discovery
      efforts.

PMID- 16814583
TI  - Production of pro-inflammatory polypeptides by airway mucous glands and its
      potential significance.
AB  - Burn patients often develop respiratory distress and ARDS several days after
      injury. An ovine model allows experimental study of this problem. In sheep the
      injury is characterized by intense acute inflammation in the trachea and bronchi
      from 3 to 48h after injury, with accumulation of neutrophils, fibrin and other
      plasma proteins, and mucus in airway lumens. We have carried out immunostaining
      for multiple cytokines in this model, including interleukin-8 (IL-8), Interleukin
      1 beta (IL-1beta), interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha
      (TNF-alpha), and vascular endothelial growth factor (VEGF). All of these show
      intense immunostaining in airway mucous glands. IL-1beta and VEGF show
      substantial constitutive staining in the serous cells of mucous glands, while IL
      8, IL-1alpha, and TNF-alpha show substantially increased expression after injury.
      This pattern of expression of cytokines in mucous glands, and the apparent
      release of cytokines into the lumen after injury, are considered potentially
      highly significant in the progression of injury in this model. In addition, a
      proinflammatory function of mucous glands might prove to be important in chronic
      lung diseases such as chronic bronchitis and asthma.

PMID- 16814584
TI  - Neuronal nitric oxide synthase in the gill of the killifish, Fundulus
      heteroclitus.
AB  - Neuronal NOS (nNOS) is a constitutively expressed enzyme that catalyzes the
      oxidation of L-arginine and water to L-citrulline and the gas nitric oxide (NO).
      Nitric oxide is involved in regulation of a variety of processes, including:
      vascular tone, neurotransmission, and ion balance in mammals and fishes. In this
      study, we have cloned and characterized a putative NOS homologue from the brain
      of the euryhaline killifish, Fundulus heteroclitus. Killifish NOS has 75% amino
      acid identity to human nNOS, and phylogenetic analysis groups the killifish
      sequence with the mammalian nNOS, suggesting that it is a mammalian orthologue.
      Relative quantitative reverse transcriptase-PCR demonstrated that killifish nNOS
      mRNA is highly expressed in the brain and gill followed by the stomach, kidney,
      opercular epithelium, intestine and heart. Immunohistochemistry localized nNOS to
      nerve fibers and epithelial cells adjacent to mitochondrion-rich cells (ion
      transporting cell) in the gill, suggesting that nNOS production of NO may
      contribute to regulation of vascular tone and/or MRC function in the teleost
      gill.

PMID- 16814585
TI  - Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into
      molecular mechanisms of CLN5 deficiency.
AB  - The neuronal ceroid-lipofuscinoses are the most common neurodegenerative
      disorders in childhood characterized by progressive blindness, epilepsy, brain
      atrophy, and premature death. Based on the age at onset, disease progression and
      ultrastructural features three classical (infantile, late-infantile, and
      juvenile) and three variant late-infantile forms are generally distinguished
      (Finnish variant, Costa Rican variant, and epilepsy with progressive motor
      retardation). The Finnish variant late-infantile form has been associated with
      CLN5 gene defects, with only five mutations described to date. We report a
      patient with vLINCL/CLN5 who represents the first evidence of the disease in the
      Portuguese population. Mutational screening revealed the previously described
      missense mutation c.835G>A (D279N) inherited from the mother, and two novel
      mutations, c.565C>T (Q189X) and c.335G>C (R112P) from paternal and maternal
      inheritance, respectively. Based on data here reported: (i) the number of
      possible mutations in CLN5 gene is now 7; (ii) the CLN5 Portuguese case
      represents the third description of the disease outside northern Europe; (iii)
      the CLN5/mRNA expression level reduced to 45% supports the existence of one mRNA
      non-producing allele, further noticeable at the protein level; (iv) Western
      blotting data using a specific antibody to human CLN5p provided evidence for the
      presence of four integral membrane isoforms in human fibroblasts; (v) data from
      differential expression of CLN2, CLN3, and CLN5 suggest down-regulation of CLN3
      gene expression in CLN2 and CLN5-deficient human patients and this observation
      strengths the hypothesis of functional redundancy of the CLN system.

PMID- 16814586
TI  - Hydatid cysts in muscle: a modified percutaneous treatment approach.
AB  - INTRODUCTION: Any organ in the human body may be affected by hydatid disease, but
      the liver and the lungs are most commonly affected. A rare localization of
      hydatid disease is within muscle tissue. Herein we present three patients with
      muscular hydatid disease who were successfully treated with a modified
      percutaneous approach. METHODS: Patients with Gharbi type III cysts were treated
      on an outpatient basis. All procedures were performed under ultrasound guidance
      in the ultrasonography unit of our department. After local anesthesia,
      percutaneous puncture was performed in a one-step procedure. After free drainage
      stopped, absolute ethanol and polidocanol were injected into the cyst cavity.
      After the procedure, the patient was observed for at least six hours for any
      adverse reactions and sent home. Patients were followed-up with ultrasonography.
      A positive treatment effect was characterized by a reduction of the cyst's pseudo
      tumor pattern and size, and by detachment of the germinal membrane. RESULTS: The
      three patients in this report had a total of five hydatid cysts in muscle tissue
      and were all successfully treated with a modified percutaneous approach without
      recurrence. CONCLUSION: Percutaneous drainage without re-aspiration is simple,
      easy to apply, low cost, repeatable, and does not require hospitalization. There
      have been no reported deaths associated with the procedure and morbidity is very
      low. When the technique is applied properly, relapses do not occur. With its low
      complication rate and its suitability for outpatient treatment, this method can
      be an alternative to surgery or puncture, aspiration, injection, and re
      aspiration (PAIR) in selected patients.

PMID- 16814587
TI  - [Efavirenz (Sustiva) in pregnancy: a study about 12 HIV patients].
AB  - OBJECTIVE: In developed countries, where the mother-to-child transmission rate of
      HIV is low (1 to 1,5%), a major medical concern is the safety of new therapies
      during pregnancy. Teratogenicity has been described with an NNRTI, efavirenz
      (Sustiva), in animal model, regarding neural tube defects. PATIENTS AND METHODS:
      We have made a retrospective study of pregnancies starting with efavirenz with a
      special focus on foetal and infant abnormalities. RESULTS: Three abnormalities
      were notified no one linked to a neural tube defect. DISCUSSION AND CONCLUSION:
      In the English literature published, although the prevalence of abnormalities in
      human is low (1,7%) during pregnancy, due to the potent teratogenicity, efavirenz
      is contraindicated in the first trimester and should be used with caution in
      women of childbearing potential.

PMID- 16814588
TI  - Effects of mesh style and grid convergence on particle deposition in bifurcating
      airway models with comparisons to experimental data.
AB  - A number of research studies have employed a wide variety of mesh styles and
      levels of grid convergence to assess velocity fields and particle deposition
      patterns in models of branching biological systems. Generating structured meshes
      based on hexahedral elements requires significant time and effort; however, these
      meshes are often associated with high quality solutions. Unstructured meshes that
      employ tetrahedral elements can be constructed much faster but may increase
      levels of numerical diffusion, especially in tubular flow systems with a primary
      flow direction. The objective of this study is to better establish the effects of
      mesh generation techniques and grid convergence on velocity fields and particle
      deposition patterns in bifurcating respiratory models. In order to achieve this
      objective, four widely used mesh styles including structured hexahedral,
      unstructured tetrahedral, flow adaptive tetrahedral, and hybrid grids have been
      considered for two respiratory airway configurations. Initial particle conditions
      tested are based on the inlet velocity profile or the local inlet mass flow rate.
      Accuracy of the simulations has been assessed by comparisons to experimental in
      vitro data available in the literature for the steady-state velocity field in a
      single bifurcation model as well as the local particle deposition fraction in a
      double bifurcation model. Quantitative grid convergence was assessed based on a
      grid convergence index (GCI), which accounts for the degree of grid refinement.
      The hexahedral mesh was observed to have GCI values that were an order of
      magnitude below the unstructured tetrahedral mesh values for all resolutions
      considered. Moreover, the hexahedral mesh style provided GCI values of
      approximately 1% and reduced run times by a factor of 3. Based on comparisons to
      empirical data, it was shown that inlet particle seedings should be consistent
      with the local inlet mass flow rate. Furthermore, the mesh style was found to
      have an observable effect on cumulative particle depositions with the hexahedral
      solution most closely matching empirical results. Future studies are needed to
      assess other mesh generation options including various forms of the hybrid
      configuration and unstructured hexahedral meshes.

PMID- 16814589
TI  - The auditory sensory epithelium: the instrument of sound perception.
AB  - The auditory sensory epithelium is the specialized region of the cochlear
      epithelium that transduces sound. It is composed of a highly ordered, repeated
      array of mechanosensory hair cells and nonsensory supporting cells that run along
      the length of the cochlea. On the apical surface of the hair cells is a
      specialized structure called the hair bundle that deflects in response to sound
      vibration, resulting in depolarization of the hair cell and neurotransmitter
      release. Formation of the auditory sensory epithelium during embryogenesis
      involves strict control of both cell proliferation and cell patterning.
      Misregulation of these events can lead to congenital hearing loss, and damage to
      the auditory sensory epithelium during adult life can lead to adult-onset
      deafness. This paper reviews recent data on the formation of the auditory sensory
      epithelium during embryogenesis, the identification of components of the sound
      transduction apparatus, and advances in the treatment of hearing impairment.

PMID- 16814590
TI  - Mitochondria are a primary target of hypericin phototoxicity: synergy of
      intracellular calcium mobilisation in cell killing.
AB  - Hypericin, a naturally occurring anthraquinone synthesised by hypericum, upon
      light activation exhibits photodynamic cytotoxicity attributed mainly to the
      production of reactive oxygen species. This study aimed to elucidate the primary
      subcellular targets and mechanistic aspects of hypericin photosensitization in
      human prostate carcinoma cells. Depletion of intracellular glutathione (>85%) via
      inhibition of gamma-glutamyl-cysteine synthase had no effect on hypericin (5
      microM) phototoxicity, thus precluding any direct oxidative involvement of H2O2.
      There was no change in intracellular SOD activity immediately after hypericin
      irradiation (1.5-5 J cm(-2)). Evaluation of the lysosomal enzyme hexosaminidase
      activity showed: (a) 60% cell loss 22 h following irradiation (1.5 J cm(-2)) and
      (b) a steady rate of lysosomal leakage to the cytosol (25%), at the same time and
      irradiation. However, lysosomal damage appears to be a slower process compared to
      the rapid loss of mitochondrial function, as reflected from parallel tetrazolium
      to formazan assays. The activity of cytosolic and mitochondrial aconitase, an
      enzyme exquisitely sensitive to oxidation, revealed a dose correlated loss of
      activity in the mitochondria immediately following hypericin photoactivation. The
      use of ionomycin, which modulates both internal Ca2+ stores and external Ca2+
      transport during hypericin photosensitization, profoundly enhanced
      photocytotoxicity. Our data supports a direct mitochondrial hypericin
      phototoxicity that does not involve glutathione/H2O2 homeostasis. Further a
      potential synergistic treatment combining mitochondrial targeting of
      photosensitisers and Ca2+ mobilisation was identified.

PMID- 16814591
TI  - Chemical biology and bacteria: not simply a matter of life or death.
AB  - Chemical biological approaches to understanding bacteria have largely been
      confined to screening for antibiotics. More complex phenotypes, such as
      virulence, have largely been studied using bacterial genetics. However, it has
      recently become clear that these two methods are complementary and that combining
      chemical biologic and genetic approaches to studying bacteria brings new power to
      old problems.

PMID- 16814592
TI  - A practical view of 'druggability'.
AB  - The introduction of Lipinski's 'Rule of Five' has initiated a profound shift in
      the thinking paradigm of medicinal chemists. Understanding the difference between
      biologically active small molecules and drugs became a priority in the drug
      discovery process, and the importance of addressing pharmacokinetic properties
      early during lead optimization is a clear result. These concepts of 'drug
      likeness' and 'druggability' have been extended to proteins and genes for target
      identification and selection. How should these concepts be integrated practically
      into the drug discovery process? This review summarizes the recent advances in
      the field and examines the usefulness of 'the rules of the game' in practice from
      a medicinal chemist's standpoint.

PMID- 16814593
TI  - Functional role of P-glycoprotein in limiting peroral drug absorption: optimizing
      drug delivery.
AB  - P-glycoprotein (P-gp) associated multi-drug resistance is one of the major
      challenges in the chemotherapy of various cancers. On the other hand, it is now
      widely recognized that P-gp influences drug transport across various biological
      membranes. To this end, there is an increasing trend to optimize pharmacokinetics
      and drug delivery right from the initial stages of drug discovery by exploring
      all the possible mechanisms involved in 'deliverability'. Recent advances in
      molecular biology techniques and biochemical characterization methodologies have
      helped in identification of various transporters involved in absorption or
      secretion of drugs. P-gp, an efflux pump expressed along the gastrointestinal
      tract, limits the permeability of many drugs and thus affects their peroral
      absorption and bioavailability. A fundamental insight and thorough understanding
      of P-gp and its functional role in limiting drug absorption is critical to
      improve predictability of dynamic absorption models and aid in selection of new
      candidates for development, and also widen the scope of peroral delivery for
      'challenging' molecules.

PMID- 16814594
TI  - A family affair: var genes, PfEMP1 binding, and malaria disease.
AB  - An immunovariant adhesion protein family in Plasmodium falciparum named
      erythrocyte membrane protein 1 (PfEMP1), encoded by var genes, is responsible for
      both antigenic variation and cytoadhesion of infected erythrocytes at blood
      microvasculature sites throughout the body. Elucidation of the genome sequence of
      P. falciparum has revealed that var genes can be classified into different
      groups, each with distinct 5' flanking sequences, chromosomal locations and gene
      orientations. Recent binding and serological comparisons suggest that this
      genomic organization might cause var genes to diversify into separately
      recombining adhesion groups that have different roles in infection and disease.
      Detailed understanding of PfEMP1 expression and receptor binding mechanisms
      during infection and of the antigenic relatedness of disease variants might lead
      to new approaches in prevention of malaria disease.

PMID- 16814595
TI  - Using non-mammalian hosts to study fungal virulence and host defense.
AB  - Non-mammalian hosts have been used to study host-fungal interactions. Hosts such
      as Drosophila melanogaster, Caenorhabditis elegans, Acathamoeba castellanii,
      Dictyostelium discoideum, and Galleria mellonella have provided means to examine
      the physical barriers, cellular mechanisms and molecular elements of the host
      response. The Drosophila host-response to fungi is mediated through the Toll
      pathway, whereas in C. elegans the host-response is TIR-1-dependent. Virulence
      traits that are involved in mammalian infection are important for the interaction
      of fungi with these hosts. Screening of fungal virulence traits using mutagenized
      fungi to determine changes in fungal infectivity of non-mammalian hosts has been
      used to identify novel virulence proteins used to infect C. elegans such as Kin1
      (a serine/threonine protein kinase) and Rom2 (a Rho1 guanyl-nucleotide exchange
      factor) from Cryptococcus neoformans. These heterologous non-mammalian hosts
      highlight the similarities and differences between different hosts in fungal
      pathogenesis and they complement studies in mammalian systems and those using
      other genetic approaches.

PMID- 16814596
TI  - Hepatitis C virus molecular clones: from cDNA to infectious virus particles in
      cell culture.
AB  - There has been major progress in our understanding of hepatitis C virus (HCV)
      molecular virology in recent years. An essential prerequisite for this progress
      was the availability of functional molecular HCV clones, that serve as a starting
      point in order to establish cell culture systems. The first of these was the HCV
      replicon system, which used self-replicating subgenomic viral RNAs. However,
      these replicons only recapitulated the intracellular life cycle, and did not
      support production of infectious virus: this became possible with the
      identification of an HCV isolate that, for unknown reasons, replicates to very
      high levels in a human hepatoma cell line. Cells containing this genome release
      virus particles that are infectious in cell culture and in vivo. Without doubt,
      this system provides new possibilities for molecular studies of the HCV life
      cycle and the development of novel antiviral concepts.

PMID- 16814597
TI  - Herpesvirus assembly: a tale of two membranes.
AB  - Herpes virions are amongst the most complex virus particles: they comprise in
      excess of thirty virally encoded proteins, and also contain cellular components.
      Capsid formation and the cleavage and encapsidation of replicated viral DNA occur
      in the nucleus and resemble similar processes in tailed dsDNA (double-stranded
      DNA) bacteriophages, which indicates they might have common ancestry. In
      contrast, final virion maturation takes place in the cytoplasm. Nucleocapsids
      gain access to this compartment by envelopment at the inner nuclear membrane,
      which involves the interaction between viral and cellular proteins in order to
      locally alter nuclear architecture. Fusion of the primary viral envelope with the
      outer nuclear membrane results in translocation of the nucleocapsid to the
      cytoplasm. Here, the majority of the tegument - a structure, composed of a
      multitude of different proteins, that links the capsid and the envelope - is
      added to nucleocapsids, which obtain their final envelope by budding into
      glycoprotein-containing Golgi-derived vesicles. Thus, herpesvirus morphogenesis
      proceeds in two different cellular compartments, involving different viral and
      cellular proteins.

PMID- 16814598
TI  - Effects of Trichinella spiralis infection on intestinal pathology in mice lacking
      interleukin-4 (IL-4) or intestinal trefoil factor (ITF/TFF3).
AB  - The nematode Trichinella spiralis induces pathological changes in the small
      intestine of the host, which are known to be controlled by immune and
      inflammatory mediators. The detail of this control has still to be completely
      understood. Mice deficient in interleukin 4 (IL-4) or in intestinal trefoil
      factor/trefoil family factor 3 (ITF/TFF3) were infected with T. spiralis and the
      resultant changes in the intestinal mucosa followed by quantifying numbers of
      mucosal mast cells, goblet cells, Paneth cells and by monitoring structural
      changes in villus length and crypt depth. Mice lacking IL-4 were unable to mount
      a normal protective response to infection, such that worm survival was increased.
      These mice failed to mount a mucosal mast cell response, but did make goblet cell
      and Paneth cell responses comparable to normal controls. Mice lacking ITF/TFF3
      similarly made normal levels of goblet cell and Paneth cell responses. They also
      underwent profound changes in mucosal architecture, with marked villus atrophy
      and crypt hyperplasia. These results are discussed in relation to known patterns
      of T cell and cytokine control of protective immunity to T. spiralis. They
      suggest that increased numbers of goblet cell and Paneth cell are not, by
      themselves, required for protective immunity. ITF/TFF3 appears not to influence
      cellular responses and does not alter parasite-induced pathological changes in
      the small intestine.

PMID- 16814599
TI  - Hydrogen bonding interaction between acrylic esters and monohydric alcohols in
      non-polar solvents: An FTIR study.
AB  - The association between acrylic esters (methyl methacrylate, ethyl methacrylate
      and butyl methacrylate) and some monohydric (primary, secondary and tertiary)
      alcohols in non-polar solvents, viz. n-heptane, CCl4 and benzene has been
      investigated by means of FTIR spectroscopy. The most likely association complex
      between alcohol and acrylic ester is 1:1 stoichiometric complex through the
      hydroxyl group of alcohol and the carbonyl group of acrylic ester. The formation
      constant of the 1:1 complexes has been calculated using Nash method. It appears
      that the primary alcohols have larger formation constant than the secondary and
      tertiary alcohols. The results show that the proton donating power of the
      alcohols decreases in the order primary>secondary>tertiary and the association
      constant increases with the increase in carbon chain of the alkyl group of
      acrylic esters and alcohols. Also the results show a significant dependence of
      the association constant upon the solvents used. The solvent effect on the
      formation of hydrogen bond equilibria is discussed in terms of specific
      interaction between the solute and solvent.

PMID- 16814600
TI  - High-resolution discrete absorption spectrum of alpha-methallyl free radical in
      the vapor phase.
AB  - The alpha-methallyl free radical is formed in the flash photolysis of 3-methylbut
      1-ene, and cis-pent-2-ene in the vapor phase, and then subsequent reactions have
      been investigated by kinetic spectroscopy and gas-liquid chromatography. The
      photolysis flash was of short duration and it was possible to follow the kinetics
      of the radicals' decay, which occurred predominantly by bimolecular
      recombination. The measured rate constant for the alpha-methallyl recombination
      was (3.5+/-0.3) x 10(10) mol(-1) ls(-1) at 295+/-2K. The absolute extinction
      coefficients of the alpha-methallyl radical are calculated from the optical
      densities of the absorption bands. Detailed analysis of related absorption bands
      and lifetime measurements in the original alpha-methallyl high-resolution
      discrete absorption spectrum image were also carried out by image processing
      techniques.

PMID- 16814601
TI  - Fourier transform infrared spectra of transition metal ion-containing
      polyanilines synthesized in different reaction conditions.
AB  - Fourier transform infrared spectroscopy has been employed to investigate the
      detailed chain structure changes during the chemical oxidative polymerisation of
      aniline in different reaction conditions including different polarity reaction
      medium, reaction temperature, reactants molar ratio and in the presence of
      different transition metal ions such as Fe2+, Co2+, Ni2+ and Cu2+. The results
      show that stronger polarity reaction medium and lower reaction temperature were
      beneficial to obtain 1,4-para-disubstituted linear chain structure polyaniline
      with higher electrical conductivity. The higher oxidation degree polyaniline
      contained more linear chain structure than that in lower oxidation degree.
      Polyanilines containing Fe2+ and Cu2+ had more linear chain structure than that
      containing Co2+ and Ni2+. These observations were in accordance with experimental
      measurements of electrical conductivity.

PMID- 16814602
TI  - A Raman spectroscopic study of synthetic giniite.
AB  - The mineral giniite has been synthesised and characterised by XRD, SEM and Raman
      and infrared spectroscopy. SEM images of the olive-green giniite display a very
      unusual image of pseudo-spheres with roughened surfaces of around 1-10microm in
      size. The face to face contact of the spheres suggests that the spheres are
      colloidal and carry a surface charge. Raman spectroscopy proves the (PO4)3- units
      are reduced in symmetry and in all probability more than one type of phosphate
      unit is found in the structure. Raman bands at 77K are observed at 3380 and
      3186cm-1 with an additional sharp band at 3100cm-1. The first two bands are
      assigned to water stretching vibrations and the latter to an OH stretching band.
      Intense Raman bands observed at 396, 346 and 234cm-1are attributed to the FeO
      stretching vibrations. The giniite phosphate units are characterised by two Raman
      bands at 1023 and 948cm-1 assigned to symmetric stretching mode of the (PO4)3-
      units. A complex band is observed at 460.5cm-1 with additional components at
      486.8 and 445.7cm-1 attributed to the nu(2) bending modes suggesting a reduction
      of symmetry of the (PO4)3- units.

PMID- 16814603
TI  - Defining and relating biomedical terms: towards a cross-language morphosemantics
      based system.
AB  - This paper addresses the issue of how semantic information can be automatically
      assigned to compound terms, i.e. both a definition and a set of semantic
      relations. This is particularly crucial when elaborating multilingual databases
      and when developing cross-language information retrieval systems. The paper shows
      how morphosemantics can contribute in the constitution of multilingual lexical
      networks in biomedical corpora. It presents a system capable of labelling terms
      with morphologically related words, i.e. providing them with a definition, and
      grouping them according to synonymy, hyponymy and proximity relations. The
      approach requires the interaction of three techniques: (1) a language-specific
      morphosemantic parser, (2) a multilingual table defining basic relations between
      word roots and (3) a set of language-independent rules to draw up the list of
      related terms. This approach has been fully implemented for French, on an about
      29,000 terms biomedical lexicon, resulting to more than 3000 lexical families. A
      validation of the results against a manually annotated file by experts of the
      domain is presented, followed by a discussion of our method.

PMID- 16814604
TI  - The effects of ageing on respiratory muscle function and performance in older
      adults.
AB  - The reduced physiological capacity evident with ageing may affect the ability to
      perform many tasks, potentially affecting quality of life. Previous research has
      clearly demonstrated the reduced capacity of the respiratory system with ageing
      and described the effect that habitual physical activity has upon this decline.
      This research aimed to examine the influence of age on respiratory muscle (RM)
      function and the relationship between RM function and physical performance within
      the Australian population. Seventy-two healthy older adults (50-79 years) were
      divided into males (n=36) and females (n=36) and examined for pulmonary function,
      RM strength, inspiratory muscle endurance (IME) and 1.6 km walking performance.
      There were no significant age by gender effects for any variables; however,
      ageing was significantly related to reduced RM function and walking capacity
      within each gender. Furthermore, regression analysis showed that the RM strength
      could be predicted from age. Partial correlations controlling for age indicated
      that expiratory muscle strength was significantly related to walking performance
      in males (p=0.04), whilst IME contributed significantly to walking performance in
      all participants. These within-gender effects and relationships indicate that RM
      strength is an important physiological variable to maintain in the older
      population, as it may be related to functional ability.

PMID- 16814605
TI  - Cancer adolescent pathway in France between 1988 and 1997.
AB  - We report an adolescent cancer pathway from referral, through diagnosis and
      treatment, to follow-up in France. All cases of cancer among 15-19 years,
      diagnosed from 1988 to 1997, recorded by nine French population-based cancer
      registries (10% of French population) were included. The management of adolescent
      cancer by paediatricians was rare. An adolescents' pathway through cancer care
      can be summarized as first visit to general practitioner, referral to adult
      oncologist for haematological malignancy and medical or surgical specialists for
      solid tumours, treatment in adult unit, and follow-up by adult oncologist, adult
      medical or surgical specialist, or general practitioner. Only 9% of the 15-19
      years are entered into a clinical trial (respectively 6% and 3% into adult and
      paediatric clinical trial). The inclusion rate changes according to the
      diagnosis, higher for acute lymphoblastic leukaemia (39%), non-Hodgkin's
      lymphomas (NHL) (27%), and acute non-lymphoblastic leukaemia (20%). Only 4% of
      adolescent cancers were managed on shared adult/paediatric departments,
      especially for soft-tissue sarcomas (14.9%), malignant bone tumours (13.4),
      central nervous system tumours (6.2%), and NHL (4.4%). Whatever the reasons for
      lack of participation in clinical trials, an ideal model requiring communication
      and cooperation between all adult and paediatric specialists involved in
      adolescent cancer treatment should reduce the large gap in access to cooperative
      groups.

PMID- 16814606
TI  - Translation and cultural adaptation of the Piper Fatigue Scale for use in Sweden.
AB  - The aim of this study was to translate and culturally adapt the revised Piper
      Fatigue Scale to Swedish. For translation, guidelines for cross-cultural
      adaptation were used. Two teams independently translated the instrument and two
      other teams produced back-translations, after which a multidisciplinary committee
      decided on a Swedish version. In pre-test interviews, ten cancer patients were
      encouraged to think out loud while completing the Swedish version. Their verbal
      responses were analysed and used for a second revision. The initial translations
      varied in words, expressions and grammar, shown in a lack of equivalence to the
      original instrument after back-translation. In order to establish semantic
      equivalence, the committee changed some grammatical constructions, and some words
      were replaced for experiential and conceptual equivalence. When analysing the pre
      test, obscurities due to the phrasing of some items were revealed and dealt with
      in the second revision. This study does not fulfil the process of validation for
      a translated instrument but offers a sound basis for further accumulation of
      evidence for validity, and facilitates the choice of an appropriate instrument
      for studying cancer-related fatigue in Sweden.

PMID- 16814607
TI  - Toll-like receptors on regulatory T cells: expanding immune regulation.
AB  - Regulatory T (Treg) cells maintain peripheral tolerance and limit effector
      responses to prevent excessive immune-mediated tissue damage. However, recent
      research reveals that Treg cells also dampen the induction of immune responses
      and, thus, must be controlled to enable the effective protection against
      infections and cancer. Until now, this control of Treg-cell function has been
      believed to be by communication through cytokines or by stimulation through co
      stimulatory molecules on antigen-presenting cells. However, new evidence has
      demonstrated that Treg cells can also sense pathogens directly through Toll-like
      receptors (TLRs) and, consequently, modify their behaviour. This review examines
      the ramifications of TLR engagement on Treg cells and conventional T cells, and
      discusses the potential role of TLRs on Treg cells and the consequences for
      disease therapy.

PMID- 16814608
TI  - Chemokine scavenging by D6: a movable feast?
AB  - The atypical chemokine receptor, D6, is efficient at sequestering and scavenging
      inflammatory CC chemokines. The absence of D6 blocks the successful resolution of
      immune responses in models of inflammation, suggesting that CC-chemokine
      scavenging by D6 is an important component of the resolution phase of in vivo
      inflammatory responses. Most studies have suggested that lymphatic endothelial
      cells are the main vehicles for D6 function in vivo. Here, we propose that
      leukocytes, which also express D6, could be more-effective vehicles for D6
      scavenging function. Thus, leukocytes might be the primary cell type that removes
      inflammatory chemokines from inflamed tissues. We also propose that lymphatic
      endothelial cell-expressed D6 might have a distinct but complementary role in
      restricting inflammatory leukocyte access to the lymphatic vasculature.

PMID- 16814609
TI  - Identification of two Melan-A CD4+ T cell epitopes presented by frequently
      expressed MHC class II alleles.
AB  - Because of its expression pattern restricted to cells of the melanocytic lineage
      and to melanoma cells, Melan-A is an important target of immunotherapeutic
      approaches for the treatment of melanoma. Identification of Melan-A derived
      sequences recognized by specific T cells is therefore of great interest for the
      development of these therapeutic strategies. Using circulating CD4(+) T cells
      from healthy donors, we identified two Melan-A-derived CD4(+) T cell epitopes
      mapping to the 1-20 and 91-110 regions of the protein and restricted by HLA-DR11
      and HLA-DR52 molecules, respectively. CD4(+) T cells specific for the identified
      epitopes were able to recognize the native antigen when endogenously expressed by
      antigen presenting cells and tumor cells. In addition, CD4(+) T cells specific
      for Melan-A 91-110 recognized the epitope after exogenous processing and
      presentation of Melan-A recombinant protein. Identification of these epitopes
      will be instrumental for the evaluation of the immune response to Melan-A in
      cancer patients.

PMID- 16814610
TI  - Construction and use of retroviral vectors encoding the toxic gene barnase.
AB  - Suicide genes for negative selection of cells have been powerful tools in somatic
      cell genetic studies and in gene therapy. Here we report on the construction,
      characterization, and utilization of retroviral vectors encoding barnase, a
      ribonuclease from Bacillus amyloliquefaciens, expression of which results in
      apoptosis of transduced mammalian cells. High-titer viral vector production was
      enabled by expression of an inhibitor of barnase (barstar) in transfected cells
      generating murine leukemia virus (MLV)- and HIV-1-based vectors. To identify
      cellular genes required for infection we used barnase-encoding vectors in a
      genetic screen to isolate mutant mammalian cells that are resistant to infection
      by MLV and HIV-1. We describe one such mutant clone that is inhibited in the
      infection process after reverse transcription. These results suggest that barnase
      encoding vectors should be useful for negative selection strategies examining
      retroviral infection from entry to integration. Furthermore these vectors could
      have utility in approaches for gene therapy that require specific cell ablation.

PMID- 16814611
TI  - Metallothionein response following cadmium exposure in the oligochaete Eisenia
      fetida.
AB  - We studied the metallothionein (MT) response in cadmium-exposed worms (Eisenia
      fetida) both at the protein level by Dot Immunobinding Assay (DIA) with a
      polyclonal antibody raised against the most immunogenic part of this protein and
      at the expression level by Northern blotting using a specific probe. MT appeared
      as two close isoforms. DIA results clearly demonstrated significant differences
      in MT level of whole worm heat-treated supernatants between E. fetida exposed to
      Cd concentrations as low as 8 mg Cd kg(-1) of dry soil compared to controls.
      Northern blotting analysis performed on whole bodies of worms revealed that a
      single exposure to 8 mg Cd kg(-1) of dry soil for 1 day resulted in the
      production of MT mRNA. This response was maintained for exposure of at least 1
      month. Clear differences of MT gene expression were also observed between worms
      exposed to different Cd concentrations (8, 80 or 800 mg Cd kg(-1) of dry soil).
      Immunocytochemistry demonstrated that MT was located in the chloragogenous tissue
      surrounding the gut where metals are known to be accumulated. This work revealed
      that E. fetida MT is a sensitive and relevant biomarker of Cd exposure and
      especially when considering gene expression response. Further experiments have
      now to prove its usefulness in natural metal-contaminated soil toxicity
      assessments.

PMID- 16814612
TI  - Video capsule endoscopy and histology for small-bowel mucosa evaluation: a
      comparison performed by blinded observers.
AB  - BACKGROUND & AIMS: In view of the excellent quality of the images obtained and
      its magnification capability, videocapsule endoscopy was proposed as a promising
      tool to evaluate the degree of duodenal villous atrophy. We studied whether the
      capsule can discriminate different degrees of mucosal damage caused by different
      conditions; we also evaluated interobserver and intraobserver variability in the
      assessment of villous atrophy with the capsule. METHODS: Thirty-two patients
      underwent both gastroscopy with multiple duodenal biopsies and videocapsule
      endoscopy. Twenty-six had different forms of celiac disease with different stages
      of villous atrophy; 5 patients had irritable bowel syndrome and 1 had Crohn's
      disease. Videocapsule findings were evaluated blindly by 3 observers. Histologic
      Marsh criteria and a specifically developed classification of videocapsule
      mucosal patterns were used to compare videocapsule findings and histology.
      RESULTS: The study of the correlation between videocapsule and histologic
      findings showed a Kappa statistic of .45, .49, and .51 for observers 1, 2, and 3,
      respectively. The sensitivity was 90.5% for observer 1 and 95.2% for observers 2
      and 3; the specificity was 63.6% for all observers. CONCLUSIONS: Videocapsule
      findings regarding the degree of intestinal mucosal atrophy show only moderate
      agreement with the histologic pattern; they have a very high sensitivity but a
      disappointing specificity. This method therefore cannot be proposed as an
      alternative to traditional biopsy examinations, but it suggests that a duodenal
      biopsy examination should be performed when an atrophic mucosal pattern is
      observed in patients undergoing videocapsule examination for other reasons.

PMID- 16814614
TI  - A tender scrotum and inguinal mass caused by pancreatitis.

PMID- 16814613
TI  - Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic
      steatohepatitis: relationship to histological improvement.
AB  - BACKGROUND & AIMS: Thiazolidinedione (TZD) therapy improves liver histology in
      nonalcoholic steatohepatitis (NASH) through a mechanism possibly related to its
      insulin-sensitizing or anti-inflammatory activity. This study was conducted to
      assess changes in serum levels of selected adipokines and proinflammatory
      cytokines and to relate these changes to the improved liver histology resulting
      from pioglitazone therapy for NASH. METHODS: Serum samples from 18 patients with
      NASH obtained at day 0 and week 48 of therapy during an open-label study of
      pioglitazone were tested for adiponectin, leptin, interleukin (IL)-1a, IL-6, and
      tumor necrosis factor (TNF)-alpha levels. Paired liver biopsy specimens were
      scored (0-4) for steatosis, parenchymal inflammation, cell injury, and fibrosis.
      RESULTS: Adiponectin levels increased from 3.7 to 10.3 mug/mL at week 48 (P <
      .01); the levels of the other cytokines were unchanged: TNF-alpha, 9.1 vs 8.8
      pg/mL; IL-1a, 3.9 vs 3.4 pg/mL; IL-6, 19.4 vs 13.4 pg/mL; and leptin, 24.8 vs
      29.6 ng/mL (P > .05 for all). Pioglitazone therapy was associated with
      improvements in steatosis (2.5 vs 1.0), parenchymal inflammation (3.3 vs 2.1),
      cell injury (2.2 vs 0.9), and fibrosis (2.0 vs 1.4). The change in adiponectin
      level was associated with the improvement in steatosis (P = .03) as well as in a
      summary NASH activity index score (P = .01). Changes in IL-1, IL-6, TNF-alpha,
      and leptin levels did not correlate with improvements in the histological
      features. CONCLUSIONS: Improvements in liver histology during TZD therapy may be
      modulated by an adiponectin-mediated effect on insulin sensitivity and hepatic
      fatty acid metabolism rather than by changes in proinflammatory cytokines.

PMID- 16814615
TI  - Comparison of antitumor activities in tumor xenograft treatment.
AB  - To compare treatment effects with antitumor therapies, we proposed an intuitive
      approach to compare the antitumor effects of two different antitumor treatments
      by investigating tumor volumes which were measured in a given period of time. The
      approach is, in essence, a comparison of two unknown functions. The
      implementation of the approach is simple and straightforward. The approach is
      applied to analyze a real xenograft study of a new antitumor agent, irofulven,
      combined with irinotecan.

PMID- 16814616
TI  - Expression of the basolateral Na-K-Cl cotransporter during mouse nephrogenesis
      and embryonic development.
AB  - We examined the expression of Slc12a2 (NKCC1) transcripts in the developing mouse
      by Northern blot analysis and in situ hybridization (ISH) using riboprobes
      transcribed from a cDNA encoding the transmembrane domain of human Slc12a2. In
      developing kidney, the 7.5-kb Slc12a2 transcript was expressed at all stages
      examined (13.5 d.p.c. to adult) but was more abundant in immature metanephroi.
      ISH revealed that NKCC1 was expressed in both mesenchymal cells and early nephric
      structures, but not branching ureteric buds, of developing metanephroi. A marked
      increase in expression was observed in the endocapillary cells of capillary loop
      stage glomeruli, and high expression was observed in the glomeruli of more mature
      nephrons. This was in contrast to Slc12a1 (NKCC2), where expression was excluded
      from the glomerulus. Extra-renal expression of Slc12a2 was examined in 13.5,
      15.5, and 16.5 d.p.c. mouse embryos. Slc12a2 was highly expressed in the
      developing lung, gut, submandibular gland, tooth bud, and nasal epithelium.
      Slc12a2 expression was also observed in the developing central and peripheral
      nervous systems, including choroid plexus and trigeminal and dorsal root ganglia.

PMID- 16814617
TI  - Ion channels of N-terminally linked alamethicin dimers: enhancement of cation
      selectivity by substitution of Glu for Gln at position 7.
AB  - Alamethicin forms voltage-gated ion channels that have moderate cation
      selectivity. The enhancement of the cation-selectivity by introducing negatively
      charged residues at positions 7 and 18 has been studied using the tethered
      homodimers of alamethicin with Q7 and E18 (di-alm-Q7E18) and its analog with E7
      and Q18 (di-alm-E7Q18). In the dimeric peptides, monomer peptides are linked at
      the N-termini by a disulfide bond. Both the peptides formed long lasting ion
      channels at cis-positive voltages when added to the cis-side membrane. Their long
      open duration enabled us to obtain current-voltage (I-V(m)) relations and
      reversal potentials at the single-channel level by applying a voltage ramp during
      the channel opening. The reversal potentials measured in asymmetric KCl solutions
      indicated that ionized E7 provided strong cation-selectivity, whereas ionized E18
      little influenced the charge selectivity. This was also the case for the
      macroscopic charge selectivity determined from the reversal potentials obtained
      by the macroscopic I-V(m) measurements. The results are accounted for by stronger
      electrostatic interactions between permeant ions and negatively charged residues
      at the narrowest part of the pore than at the pore mouth.

PMID- 16814618
TI  - Development of cholesterol biosensor based on immobilized cholesterol esterase
      and cholesterol oxidase on oxygen electrode for the determination of total
      cholesterol in food samples.
AB  - The development of a cholesterol biosensor by co-immobilization of cholesterol
      esterase (ChEt) and cholesterol oxidase (ChOX) on oxygen electrode is described.
      The electrode consists of gold cathode and Ag/AgCl anode. The enzymes were
      immobilized by cross-linking with glutaraldehyde and Bovine Serum Albumin (BSA).
      The immobilized enzymatic membrane was attached to the tip of the electrode by a
      push cap system. The optimum pH and temperature of the sensor was determined,
      these are 6 and 25 degrees C respectively. The developed sensor was calibrated
      from 1-75 mg/dl of cholesterol palmiate and found linear in the range of 2-50
      mg/dL. The calibration curve was drawn with V(i) (ppm/min)(initial velocity) vs
      different concentrations of cholesterol palmiate (mg/dL). The application of the
      sensor to determine the total cholesterol in different real food samples such as
      egg, meat was investigated. The immobilized enzymatic layer can be reused over 30
      times and the stability of the enzymatic layer was studied up to 9 weeks.

PMID- 16814619
TI  - Studies on chromosome aberration induction: what can they tell us about DNA
      repair?
AB  - Many, if not the majority of spontaneous or induced mutations in somatic
      mammalian cells associated with cancer are large chromosome level changes. For
      exposure to carcinogenic agents, certain specific chromosomal aberrations are
      likely to lie early along the pathway leading from initial molecular damage to
      cancer. The kinds of aberrations that occur, and the positions of breakpoints
      involved in their formation, can reveal not only genes and controlling elements
      whose expression or suppression underlie the molecular nature of the initiation
      of malignant transformation, but also how structural and functional features of
      chromatin can affect processes involved in repair or mis-repair of initial DNA
      damage. Thus, cytogenetics can provide information in ways that are not readily
      appreciated in studies requiring disruption of chromatin organization as it
      exists in the cell and its tissue context, and where DNA repair assays measure
      effects averaged over the entire genome. Examples include the fact that in
      contrast to a more efficient repair of single strand or base damage in
      transcriptionally active chromatin, after ionizing radiation exposure, the
      preponderance of translocation breakpoints indicating mis-repair occur in
      transcriptionally active or potentially active chromatin. Cytogenetic studies
      have led to the recognition that processing of DNA ends - both ends resulting
      from breaks along chromosomes and natural chromosomal termini, or telomeres -
      share very interesting similarities and differences. Further, direct observation
      of chromatin in cells during interphase can speak directly to early stages of
      aberration formation where processes occur within the context of intact cells,
      and to the role (or lack thereof) of cell cycle checkpoint responses that often
      accompany DNA damage. The superior resolution of many of the current molecular
      cytogenetics approaches, combined with immunocytochemical detection of proteins
      involved in DNA damage processing, and the availability of repair deficient
      mutants or knockdown strategies such as RNA interference, suggest that
      cytogenetics may still provide useful information and set certain restrictions
      important for rational interpretation of studies of DNA repair and associated
      protein interactions that can only be carried out in vitro. The intent of this
      paper is to focus on contributions of studies on the production of chromosomal
      aberrations following ionizing radiation exposure regarding important insights on
      associated DNA repair processes involved, and further, on guidelines or
      constraints they provide for the interpretation of in vitro DNA repair studies
      that would have been difficult to appreciate without the cytogenetics. We will
      first briefly summarize some early studies that serve as a reminder of the
      background on which current studies are based, and then carry forward to the
      present day certain interesting facets of these studies.

PMID- 16814620
TI  - Endogenous expression of phosphorylated histone H2AX in tumors in relation to DNA
      double-strand breaks and genomic instability.
AB  - Microscopically visible gammaH2AX foci signify the presence of DNA double-strand
      breaks (dsbs) in irradiated cells. However, large foci are also observed in
      untreated tumour cells, and high numbers reduce the sensitivity for detecting
      drug or radiation-induced DNA breaks. SW756 cervical carcinoma cells that express
      about 50 gammaH2AX foci per cell (i.e., equivalent to the number of breaks
      produced by about 2Gy) showed similar numbers of dsbs as C33A cells that exhibit
      fewer than three foci per cell. The possibility that differences in numbers of
      these endogenous foci could be explained by genomic instability perhaps related
      to misrepair was examined. For 17cell lines selected from the panel of NCI-60
      tumor cells previously characterized for karyotypic complexity [A.V. Roschke, G.
      Tonon, K.S. Gehlhaus, N. McTyre, K.J. Bussey, S. Lababidi, D.A. Scudiero, J.N.
      Weinstein, I.R. Kirsch, Karyotypic complexity of the NCI-60 drug-screening panel,
      Cancer Res. 63 (2003) 8634-8647], there was a significant trend (r=0.6) for cell
      lines with greater numbers of structural or numerical chromosomal rearrangements
      to show a higher background expression of gammaH2AX. Moreover, cells from this
      panel with wild-type p53 showed a significantly lower background level of
      gammaH2AX than cells with mutant p53. To confirm the importance of p53
      expression, endogenous and radiation-induced gammaH2AX expression were analyzed
      using four isogenic SKOV3 cell lines varying in p53 function. Again, higher
      gammaH2AX expression was found in SKOV3 cell lines expressing mutant p53 compared
      to wild-type p53. HFL-1 primary lung fibroblasts showed a progressive increase in
      gammaH2AX as they moved towards senescence, confirming the importance of telomere
      instability in the development of at least some gammaH2AX foci. Therefore, the
      explanation for high endogenous levels of gammaH2AX in some tumor cells appears
      to be multifactorial and may be best described as a consequence of chromatin
      instability.

PMID- 16814621
TI  - On-line biological sample cleanup for electrospray mass spectrometry using sol
      gel columns.
AB  - Using a slight overpressure, a urine sample is loaded onto a monolithic
      photopolymerized sol-gel column that has been derivatized with hydrophobic carbon
      chains and then the complex urine matrix is washed with aqueous solution. A
      buffer containing organic solvent is used to elute the adsorbed peptides by an
      applied voltage and the sample is then introduced into a mass spectrometer by
      sheath flow electrospray. The importance of desalting this type of sample is
      demonstrated by an experiment that shows that the signal intensity of a test
      solution with neurotensin, sprayed directly into the mass spectrometer, decreased
      from 4.5x10(4) cps to no detectible signal when just 10% urine is added to the
      sample solution. We suggest that this procedure may find general application for
      desalting biological samples prior to mass spectrometric analysis.

PMID- 16814622
TI  - Raloxifene enhances vertebral mechanical properties independent of bone density.
AB  - Anti-remodeling agents produce similar reductions in vertebral fracture risk
      despite large differences in BMD changes suggesting the mechanism of fracture
      risk reduction may differ among these agents. Forty-eight intact (non
      ovariectomized) skeletally mature female beagle dogs were treated orally for 12
      months with clinically relevant doses of risedronate (RIS, 0.10 mg/kg/day),
      alendronate (ALN, 0.2 mg/kg/day), raloxifene (RAL, 0.50 mg/kg/day), or saline
      (VEH, 1 ml/kg/day). After sacrifice, the following measurements were made on
      vertebral bone: areal (aBMD) and volumetric (vBMD) bone mineral densities, tissue
      mineralization by ash content, static and dynamic histomorphometric parameters,
      microdamage, and extrinsic and intrinsic measures of biomechanical strength,
      stiffness and energy to fracture. At these doses, RAL suppressed bone turnover (
      20%) significantly less than the bisphosphonates (-66 and -71%) and did not
      produce significant differences in aBMD, vBMD, BV/TV or percent ash compared to
      VEH-treated animals. Microdamage accumulation in RAL-treated animals was not
      significantly different than VEH; both RIS and ALN had significantly higher crack
      surface density compared to VEH. Stiffness was significantly higher than VEH in
      all treatment groups. Ultimate load divided by aBMD, a measure of strength
      independent of BMD, was significantly higher only in RAL-treated animals compared
      to VEH (+16%, P = 0.015). Based on these data, we conclude that raloxifene
      produces improvements in bone mechanical properties in ways that do not involve
      increases in BMD.

PMID- 16814624
TI  - An editorial on "Mental health care for adults with suicide ideation".

PMID- 16814623
TI  - Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone
      turnover markers, bone mineral density, and vitamin D receptor genotype in
      Emirati women.
AB  - OBJECTIVES: To determine factors influencing serum 25 hydroxyvitamin D (25OHD)
      concentration and relationships between serum 25OHD concentration, bone turnover
      markers, bone mineral density (BMD), and vitamin D receptor (VDR) genotype in
      Emirati women. METHODS: Serum 25OHD, parathyroid hormone (PTH), osteocalcin (OC),
      vitamin D binding protein (VDBP), and urinary deoxypyrdinoline (UDPD)
      concentrations and VDR genotype were determined in Emirati women volunteers who
      were participating in a study aiming at establishing a reference database for
      BMD. RESULTS: Serum 25OHD concentration in the 259 women volunteers was 25.3 +/-
      10.8 nmol/l (mean +/- SD), and all had vitamin D deficiency (25OHD <80 nmol/l).
      Mean serum 25OHD was highest in April (29.2 +/- 13.0 nmol/l), which marks the end
      of the short and cooler winter season, and lowest in August (18.2 +/- 5.9
      nmol/l). No significant difference in 25OHD concentration was noted among Emirati
      women wearing different dress styles, but the mean serum 25OHD was significantly
      lower in comparison with non-Arab Caucasian women volunteers who dressed in a
      Western style (P < 0.001). Serum 25OHD correlated positively with age (r = 0.2),
      number of pregnancies (r = 0.16), dietary vitamin D intake (r = 0.15), serum
      calcium (r = 0.14), phosphorus (r = 0.14), VDBP (r = 0.15), and urinary
      calcium/creatinine (r = 0.2), and inversely with PTH (r = -0.22), OC (r = -0.13),
      and UDPD/creatinine (r = -0.15); P < 0.05 for all correlations. Multiple linear
      regression analysis showed that age, dietary vitamin D intake, multivitamin
      intake, and cooler season were independent positive predictors of serum 25OHD
      concentration (R(2) = 0.18). The frequencies of VDR genotypes were 36% GG, 44.1%
      AG, and 19.9% AA. Allele frequencies were 58% for G allele and 42% for A allele
      and were in Hardy-Weinberg equilibrium (x(2) = 1.44; P > 0.1). There was no
      statistically significant influence of VDR genotype on bone turnover or BMD.
      CONCLUSIONS: Vitamin D deficiency is highly prevalent in Emirati women and
      appears largely attributable to insufficient sunlight exposure. It is associated
      with increased bone turnover. VDR genotype does not appear to influence bone
      turnover markers or BMD in Emirati women.

PMID- 16814625
TI  - Mental health care for adults with suicide ideation.
AB  - OBJECTIVE: To estimate mental health and substance abuse services use for adults
      with and without suicide ideation. METHOD: 2000-2001 follow-up of respondents to
      a nationally representative survey. Measures include self-reports of suicide
      ideation, specialty and primary care mental health services use, past year
      counseling, psychotropic medications and perceived need. RESULTS: The percentage
      of respondents who reported suicide ideation was 3.6%; 74% of them had a probable
      psychiatric disorder for which effective treatments exist. Nearly half of those
      with suicide ideation did not perceive a need for care, including some who
      received care. Of those with suicide ideation and a probable disorder, almost 40%
      received no treatment. Of those with suicide ideation who perceived a need for
      alcohol, drug or mental health (ADM) care, almost 40% received no care or
      inadequate care. In a multivariate model, having a probable psychiatric disorder,
      perceived need and being white were associated with increased likelihood of
      treatment use, among persons with suicide ideation. CONCLUSIONS: Many adults with
      suicide ideation do not perceive a need for care or receive treatment in the same
      year. Even among those perceiving a need for care, many experience difficulties
      in obtaining it. It is critical to understand barriers to treatments for this
      high-risk group.

PMID- 16814626
TI  - Funding mechanisms for depression care management: opportunities and challenges.
AB  - OBJECTIVE: Inconsistent third-party reimbursement for depression care management
      is a significant economic barrier to the utilization and sustainability of the
      chronic illness care model in primary care practice settings. We review common
      mechanisms used to procure payment for depression care management services,
      discuss obstacles encountered and suggest future directions. METHOD: We describe
      several extant models for funding depression care management services in use at
      the demonstration sites of the Robert Wood Johnson Foundation funded "Depression
      in Primary Care" project and similar programs. We derived this information from
      ongoing discussions with the sites' project directors and through an extensive
      electronic literature search on "care management, funding mechanisms and
      depression." RESULTS: Funding mechanisms include (a) practice-based care
      management on a fee-for-service basis, (b) practice-based care management under
      contract to health plans, (c) global capitation, (d) flexible infrastructure
      support for chronic care management, (e) health-plan-based care management, (f)
      third-party-based care management under contract to health plans and (g) hybrid
      models. CONCLUSIONS: While substantial obstacles remain in the way of fully
      implementing these depression care management funding mechanisms (e.g.,
      variations in care managers' credentials and work locations and third-party payer
      concerns about overutilization and transaction costs), several recent policy
      advances provide some optimism for the potential adoption of financial mechanisms
      to support and disseminate these evidence-based practices.

PMID- 16814627
TI  - Rates and predictors of depression treatment among pregnant women in hospital
      affiliated obstetrics practices.
AB  - OBJECTIVE: The purpose of this study was to provide information on rates of
      depression treatment among pregnant women at risk for depression and among those
      with clinician-diagnosed current major depressive disorder (MDD) and to examine
      predictors of depression treatment. METHOD: Women seeking prenatal care completed
      a screening survey (including the Center for Epidemiological Studies-Depression
      Scale) in several hospital-based obstetrics clinics. Women identified as high
      risk for depression completed diagnostic interviews (n=276) during pregnancy,
      consisting of the Structured Clinical Interview for DSM-IV, measures of
      depression symptom severity (Beck Depression Inventory-II), health functioning
      (SF-36) and current and past psychiatric treatment. RESULTS: Among women with a
      current MDD diagnosis, most of whom were experiencing a recurrence, 33% were
      currently receiving any depression treatment. The presence of current MDD was not
      found to be related to use of treatment. Prior history of MDD, history of
      psychiatric treatment and depression severity were significant predictors of
      depression treatment during pregnancy. CONCLUSIONS: Most women with current MDD
      were found to be either untreated or suboptimally treated, and prenatal MDD was
      not predictive of treatment. These findings point to the need for effective
      detection, targeted follow-up assessment and treatment linkage interventions to
      be studied in medical settings that encounter perinatal women.

PMID- 16814628
TI  - Developing a U.K. protocol for collaborative care: a qualitative study.
AB  - OBJECTIVE: This study aimed to explore the views of stakeholders including
      patients, general practitioners (GPs) and mental health workers on the
      feasibility, acceptability and barriers to a collaborative care model for
      treatment of depression within the context of U.K. primary health care. METHOD:
      We used semistructured interviews and focus groups with a purposive sample of 11
      patients and 38 professionals from a wide selection of primary and secondary care
      mental health services, as well as framework analysis using a "constant
      comparative" approach to identify key concepts and themes. RESULTS: Regular
      contact for patients with depression is acceptable and valued by both patients
      and professionals. However, patients value support, whereas professionals focus
      on information. To be acceptable to patients, contacts about medication or
      psychosocial support must minimize the potential for patient disempowerment. The
      use of the telephone is convenient and lends anonymity, but established mental
      health workers think it will impair their judgments. While patients merely
      identified the need for skilled case managers, GPs preferred established
      professionals; however, these workers did not see themselves in this role. All
      involved were cautious about deploying new workers. Additional barriers included
      practical and organizational issues. CONCLUSIONS: Although a telephone-delivered
      mix of medication support and low-intensity psychological intervention is
      generally acceptable, significant issues to be addressed include the values of
      the current mental health workforce, fears about new workers' experience and
      competence, the balance of face-to-face and telephone contacts and case manager
      education in nonspecific skills necessary to develop a therapeutic alliance, as
      well as the knowledge and skills required for education, medication support and
      behavioral activation. Qualitative research can add value to careful modeling of
      collaborative care prior to international implementation.

PMID- 16814629
TI  - Characteristics of depression in hemodialysis patients: symptoms, quality of life
      and mortality risk.
AB  - BACKGROUND: Depression is often underrecognized in patients with end-stage renal
      disease. We interviewed outpatients at an urban dialysis facility using a
      criterion-based case-finding instrument to assess the rates, clinical correlates
      and outcomes of depression. METHODS: The Primary Care Evaluation of Mental
      Disorders Mood Module and the nine-item Patient Health Questionnaire were used to
      assess depression. We measured health-related quality of life using the Kidney
      Disease and Quality of Life Short Form, and medical comorbidities were measured
      using the Charlson Comorbidity Index. We compared the sociodemographic and
      clinical characteristics and health-related quality of life of depressed and
      nondepressed patients using t tests and the chi-square test, and we used a Cox
      regression model to test the relationship between depression and mortality.
      RESULTS: We interviewed 62 patients and followed them for a mean of 29 months
      (range, 0.1-36). Seventeen (28%) had major or minor depression. Depressed
      patients were younger and had lower health-related quality of life than did
      nondepressed patients. Depression predicted mortality (HR=4.1, 95% CI=1.5-32.2,
      P<.05) after adjusting for age, gender, race, medical comorbidities, albumin,
      kt/V and/or the presence of diabetes. CONCLUSIONS: Depression is common and
      associated with decreased health-related quality of life and increased mortality
      in hemodialysis patients. Clinical trials are necessary to examine whether
      treatment of depression can improve these outcomes.

PMID- 16814630
TI  - Associations between depressive symptoms and obesity during puberty.
AB  - BACKGROUND: Adolescent depression has been shown to be associated with later
      development of obesity. The purpose of this study was to examine the association
      between depressive symptoms and obesity with progressive pubertal development.
      METHODS: We conducted an analysis of the association between depressive symptoms
      and obesity using data from a cross-sectional study of 3101 youth aged 11-17
      years. Logistic regression analyses were used to control for maternal education
      level, race and age. Analyses were stratified by pubertal status and sex to
      examine how the relationship between depressive symptoms and obesity varies with
      pubertal development. RESULTS: Depressive symptoms increased with pubertal
      development for both boys and girls, but the increase was larger for girls.
      Obesity prevalence was similar for all categories of pubertal development in boys
      and girls. After controlling for age, pubertal development, parental education
      and race, an association was noted between depressive symptoms and obesity among
      both males and females. Youth above the 90th percentile in the depressive symptom
      score had two times the odds of being obese [males: odds ratio (OR)=1.95, 95%
      confidence interval (95% CI)=1.19-3.18; females: OR=2.17, 95% CI=1.25-3.77]. With
      the exception of males in late puberty (OR=0.91, 95% CI=0.29-2.87), the magnitude
      of this association between depressive symptoms and obesity was similar for all
      levels of pubertal development, with no apparent increase in later puberty among
      girls. CONCLUSION: Depressive symptoms and obesity were associated during
      adolescence, and this association did not increase with advancing pubertal
      development.

PMID- 16814631
TI  - Evaluation of a one-question interview for depression in a radiation oncology
      department in Japan.
AB  - This study aims to clarify the validity of the brief screening measure of
      depression in Japan. It was the single-item interview "Are you depressed?" that
      provided a reliable and remarkable accurate screen in North America. The study
      was conducted on 282 participants receiving radiotherapy for cancer. The
      criterion diagnosis were given by the Structured Clinical Interview for DSM
      (SCID). On the basis of the receiver operating characteristic (ROC) analyses, we
      compared the results obtained using single-item interview with major and minor
      depressive disorders defined by DSM-TR and calculated the sensitivity,
      specificity and likelihood ratio (LR). The result of the present study indicated
      a sensitivity of 42% (95% CI 22-61%) and a specificity of 86% (95% CI 82-91%),
      and LR of 3.1. In conclusion, single-item interview "Are you depressed?" did not
      have sufficient sensitivity.

PMID- 16814632
TI  - Routine use of the Beck Scale for Suicide Ideation in a psychiatric emergency
      department.
AB  - BACKGROUND: U.S. suicide rates are estimated to be 11 per 100,000 people, and
      improved screening in emergency departments may reduce suicide rates. METHOD:
      This study examined the relationship between clinician rating of suicide ideation
      and Beck Scale for Suicide Ideation (BSI) scores when clinicians had access to
      the BSI results and whether BSI scores and/or clinician ratings of suicidality
      are associated with patient disposition from the psychiatric emergency
      department. RESULTS: Of 735 patients, 665 (90%) had documentation of suicide
      ideation in the chart; 246 (37%) were rated as suicidal; 487 (66%) patients
      completed the BSI forms; 300 patients (62%) scored positive on the BSI. Logistic
      regression analysis for BSI scores and clinician ratings of suicidality showed
      similar results, except clinicians were more likely to rate males as suicidal,
      while BSI scores did not vary according to sex. Hospitalization occurred more
      often for patients with mood disorder who had positive BSI scores, while
      hospitalization occurred more often for patients with a diagnosis of bipolar
      disorder or schizophrenia who were rated by clinicians as suicidal. CONCLUSIONS:
      There were important demographic and diagnostic differences revealed by logistic
      regression analysis of BSI scores and clinician-rated suicidality, and these
      differences may be associated with disposition for patients presenting with
      suicide ideation.

PMID- 16814633
TI  - Accuracy of diagnosis at routine psychiatric assessment in patients presenting to
      an accident and emergency department.
AB  - OBJECTIVE: This study aimed to compare diagnoses obtained from routine
      psychiatric assessment in accident and emergency (A&E) settings with those from a
      standardized diagnostic interview. METHODS: Using Cohen's kappa, the agreement
      between diagnoses from routine psychiatric assessment and structured interview
      was calculated. Further statistical analysis was used to investigate differences
      between some of the main diagnostic subgroups. RESULTS: The overall kappa value
      for all diagnoses was .47. Adjustment disorder, major depressive disorder and
      alcohol misuse/dependence were commonly identified, both at routine assessment
      and on structured interview. There was a disparity between the two diagnostic
      systems in the extent to which major depressive disorder and adjustment disorder
      were identified. Further analysis between these two groups was inconclusive as to
      the reasons for this difference. CONCLUSIONS: There was moderate agreement
      between clinical and standardized diagnoses. Anxiety disorders were poorly
      identified at routine assessment. There is difficulty distinguishing between
      adjustment disorder and depressive episode in the A&E setting.

PMID- 16814634
TI  - Availability, content and quality of local guidelines for the assessment of
      suicide attempters in university and general hospitals in the Netherlands.
AB  - OBJECTIVE: This study was performed to investigate the availability, content and
      quality of local guidelines for the assessment of suicide attempters in the
      Netherlands. METHOD: All university and general hospitals in the Netherlands were
      asked to provide their local guidelines. Published national guidelines and the
      Appraisal of Guidelines for Research and Education (AGREE) instrument were used
      to evaluate the content and quality of the local guidelines. RESULTS: Eighty
      eight hospitals (90.7%) responded; 34 (38.6%) reported that they used local
      guidelines. Twenty-seven guidelines were submitted for evaluation. Most of the
      guidelines were more than 5 years old and had not been updated recently. The
      contents of the guidelines differed. Criteria addressing patient safety, staff
      attitude toward patients, reassessment of nonalert patients, relevant stressors,
      involvement of significant others and aftercare were found in less than 50% of
      the guidelines. Although psychiatric consultation was incorporated in almost 80%,
      the psychiatrist's tasks were specified infrequently. The guidelines seldom
      required monitoring of staff compliance. Only in the AGREE domain "clarity and
      presentation" was the mean score above 60% of the maximum. According to the
      instructions for the AGREE instrument, 10 (37.0%) of the 27 guidelines were
      recommended (with provisos or alterations) and 1 was strongly recommended for use
      in practice. CONCLUSIONS: In the Netherlands, a minority of hospitals reported
      use of local guidelines for the assessment of suicide attempters. When available,
      the guidelines were mostly not based on international standards, their contents
      varied greatly and their quality was unsatisfactory.

PMID- 16814635
TI  - Turning theory into practice: rationale, feasibility and external validity of an
      exploratory randomized controlled trial of training family practitioners in
      reattribution to manage patients with medically unexplained symptoms (the MUST).
AB  - BACKGROUND: The evidence for the effectiveness of reattribution training are
      limited, and optimal service delivery is not yet established. OBJECTIVES: The
      objectives of this study were to establish the feasibility and to optimize the
      service delivery and design of a definitive randomized controlled trial (RCT) of
      reattribution training for patients with medically unexplained symptoms (MUSs) in
      routine primary care. METHODOLOGY: The study was of a cluster RCT design with the
      practice as the unit of randomization. Health facilitator (HF)-delivered
      reattribution training was compared with no reattribution training. The primary
      outcome measure used is doctor-patient communication in the consultation.
      Quantitative and qualitative methods identify barriers to effectiveness. The
      acceptability and feasibility of the intervention were established by attendance
      rates and postal survey after completion of training. RESULTS: Sixteen practices
      and 70 family practitioners (FPs) were recruited with representative practice and
      FP characteristics. Six hours of HF reattribution training to FPs in the
      workplace proved feasible and acceptable with all 35 FPs completing the training.
      Feedback from 27 (77%) FPs who received training indicated that 25 (93%) FPs
      believed that specific and relevant learning achievements were made, 22 (82%)
      felt more confident and 21 (77%) thought the training was useful. CONCLUSION: HF
      delivered reattribution training to whole practices is feasible and acceptable,
      and its effectiveness is measurable in routine primary care.

PMID- 16814636
TI  - Demographics of and diagnoses in Operation Enduring Freedom and Operation Iraqi
      Freedom personnel who were psychiatrically evacuated from the theater of
      operations.
AB  - OBJECTIVE: The objective of this study was to characterize the demographic and
      clinical information of Operation Enduring Freedom (OEF) and Operation Iraqi
      Freedom (OIF) military personnel who were psychiatrically evacuated from the
      theater of operations. METHOD: Records of 1264 consecutive OEF/OIF patients who
      were medically evacuated for primarily psychiatric reasons between November 4,
      2001, and July 30, 2004, were reviewed to collect demographic information and
      psychiatric diagnoses. RESULTS: When compared with all returned OEF/OIF veterans
      (N=213,150), psychiatric evacuees were more likely to be: female, under the age
      of 31 years, African-American or Hispanic, enlisted and National Guard/Reserve.
      Over 80% of patients were evacuated during the first 6 months, compared with 17%
      during the second 6 months of deployment. The most common diagnostic categories
      were adjustment disorders (37.6%), mood disorders (22.1%), personality disorders
      (15.7%) and anxiety disorders (15.4%); 16.5% received no psychiatric diagnosis.
      Only 5% of evacuees were returned to OEF/OIF duty. CONCLUSION: Almost half of
      evacuated patients received no diagnosis or no adjustment disorder diagnosis,
      suggesting clinical improvement since a decision for evacuation was made.
      Potential areas of focus for preventing psychiatric evacuations are identifying
      service members who are at risk during early stages of deployment and studying
      whether there are gender-specific deployment stressors.

PMID- 16814637
TI  - Interferon-induced obsessive-compulsive disorder.

PMID- 16814638
TI  - Quetiapine vs. risperidone in treating psychosis in neurosyphilis: a case report.
AB  - OBJECTIVE: A 44-year-old male patient presented with agitation, auditory
      hallucinations, and delusions of persecution was diagnosed as having
      neurosyphilis. METHODS: He was treated with penicillin G 24 million units/day,
      risperidone 6 mg/day, and memantine 20 mg/day with partial response to psychotic
      symptoms and significant extrapyramidal symptoms. RESULTS: On his follow-up,
      after 5 months, his cognitive status and serological tests remained the same, and
      his cell count was increased. A second therapy of penicillin was administered
      without any clinical improvement. On his second hospitalization for severe
      psychotic agitation after approximately 1 year, quetiapine 1200 mg/day was
      introduced and the psychiatric state improved immediately without significant
      side effect. CONCLUSIONS: Quetiapine, which has a low potential for producing
      extrapyramidal side effects, should be considered in the treatment of psychotic
      symptoms of neurosyphilis.

PMID- 16814639
TI  - Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a
      case report.
AB  - In this case report, even a moderate dose of dexmedetomidine, a very selective
      alpha(2)-adrenergic agent, resulted in a rapid response to alcohol withdrawal
      delirium after the standard treatment. Psychiatrists should be aware of this
      relatively new drug that provides advantages over clonidine, heavy sedation and
      secondary restraints. Dexmedetomidine should be further evaluated in the
      treatment of specific forms of aggressive behavior and complicated withdrawal
      states.

PMID- 16814640
TI  - A novel treatment option of bipolar depression with psychotic and catatonic
      features.

PMID- 16814641
TI  - Biomarkers in acute cardiac disease: the present and the future.
AB  - The use of biomarkers to aid diagnosis and treatment is increasing rapidly as
      genomics and proteomics help us expand the number of markers we can use and as an
      improved understanding of the pathophysiology of cardiac disease guides their
      use. However, as with all rapidly expanding fields, there is the risk of
      excessive enthusiasm unless we are circumspect about the data that guide the
      clinical use of these new tools. This review focuses first on how to use
      troponin, which at present is the best validated of the new markers, and will
      hopefully provide insight into how to use this biomarker more productively by
      distinguishing subsets of patients and by providing an understanding of the
      meaning of elevations in various clinical situations. The review then discusses
      the use as well as the knowledge gaps associated with emerging biomarkers such as
      B-type natriuretic peptide and C-reactive protein, which are increasingly moving
      toward more productive clinical use. Finally, it reflects on some of the large
      number of markers that are still in development.

PMID- 16814642
TI  - Prescribing BiDil: is it black and white?
AB  - The approval of BiDil as an adjunct treatment in self-identified blacks with
      heart failure raises questions regarding the underlying etiology of drug response
      in this target population and the ability to accurately identify patients who are
      most likely to benefit. Preliminary data have indicated that differences in
      nitric oxide synthesis between groups may account for differences in response to
      BiDil and genetic studies have begun to elucidate the mechanism of these
      differences. Until more accurate selection criteria are developed to identify
      patients who are most likely to benefit, both clinicians and the general public
      will need to consider the unique issues raised by BiDil.

PMID- 16814643
TI  - Effects of selective matrix metalloproteinase inhibitor (PG-116800) to prevent
      ventricular remodeling after myocardial infarction: results of the PREMIER
      (Prevention of Myocardial Infarction Early Remodeling) trial.
AB  - OBJECTIVES: We sought to determine whether matrix metalloproteinase (MMP)
      inhibitor, PG-116800, reduced left ventricular (LV) remodeling after myocardial
      infarction (MI). BACKGROUND: PG-116800 is an oral MMP inhibitor with significant
      antiremodeling effects in animal models of MI and ischemic heart failure.
      METHODS: In an international, randomized, double-blind, placebo-controlled study,
      253 patients with first ST-segment elevation MI and ejection fraction between 15%
      and 40% were enrolled 48+/- 24 h after MI and treated with placebo or PG-116800
      for 90 days. Major efficacy end points were changes in LV volumes as determined
      by serial echocardiography, and clinical and safety outcomes were also collected.
      RESULTS: In total, 203 patients (80%) completed 90 days of treatment and had
      evaluable baseline and 90-day echocardiograms. The proportion of patients with
      anterior MI (78% vs. 81%) and primary percutaneous coronary intervention (90% vs.
      91%) along with baseline LV ejection fraction (35.5% vs. 36.8%) did not differ
      between PG-116800-treated and placebo-treated patients. There was no difference
      in the change in LV end-diastolic volume index from days 0 to 90 with PG-116800
      versus placebo (5.09 +/- 1.45 ml/m(2) vs. 5.48 +/- 1.41 ml/m2, p = 0.42). Changes
      in LV diastolic volume, LV systolic volume, LV ejection fraction, sphericity
      index, plus rates of death or reinfarction were not significantly improved with
      PG-116800. PG-116800 was well tolerated; however, there was increased incidence
      of arthralgia and joint stiffness without significant increase in overall
      musculoskeletal adverse events (21% vs. 15%, p = 0.33). CONCLUSIONS: Matrix
      metalloproteinase inhibition with PG-116800 failed to reduce LV remodeling or
      improve clinical outcomes after MI.

PMID- 16814644
TI  - Periprocedural and late consequences of overlapping Cypher sirolimus-eluting
      stents: pooled analysis of five clinical trials.
AB  - OBJECTIVES: The purpose of this research was to determine the relative safety and
      efficacy of multiple (> or =2) overlapping Cypher sirolimus-eluting stents (SES)
      (Johnson & Johnson, New Brunswick, New Jersey). BACKGROUND: Overlapping coronary
      stents are common. The periprocedural and late clinical and angiographic
      consequences of overlapped coronary stents are not clearly defined, particularly
      for drug-eluting stents. METHODS: All patients enrolled into five clinical trials
      of the SES were analyzed. Three of these trials were prospective randomized
      comparisons of the SES to the bare-metal stent (BMS), and two were prospective
      non-randomized trials of SES-treated patients with historical controls. All
      clinical and angiographic outcomes in overlap-stent-treated patients were
      compared by stent type and with single-stent-treated patients for the same stent
      device. RESULTS: In all, 575 patients with stent overlap (337 SES, 238 BMS) and
      1,162 patients with single stents (697 SES, 465 BMS) were analyzed. Stent overlap
      was associated with a greater late lumen loss in stent and more frequent
      angiographic restenosis regardless of stent type. Among overlap-stent-treated
      patients, the SES provided similar magnitude of restenosis benefit as observed
      for single-stent-treated patients. Overlapped SES was not associated with an
      increase in myocardial infarction. CONCLUSIONS: The strategy of SES overlap, when
      required, is both safe and efficacious in reducing restenosis with no increase in
      the incidence of myocardial infarction or major adverse cardiovascular events,
      when compared with a bare metal coronary stent prosthesis.

PMID- 16814645
TI  - Impact of routine angiographic follow-up on the clinical benefits of paclitaxel
      eluting stents: results from the TAXUS-IV trial.
AB  - OBJECTIVES: The objectives of the study were to evaluate the effect of
      angiographic follow-up on revascularization rates in the TAXUS-IV trial and to
      determine whether the relative benefit of paclitaxel-eluting stent implantation
      compared with bare metal stent implantation was modified by angiographic follow
      up. BACKGROUND: Although several clinical trials have demonstrated that drug
      eluting stents (DES) reduce restenosis compared with bare-metal stents (BMS),
      virtually all of these studies have incorporated angiographic follow-up. METHODS:
      In the TAXUS-IV trial, 1,314 percutaneous coronary intervention patients were
      randomized to receive paclitaxel-eluting stents (PES) (n = 662) or identical
      appearing BMS (n = 652). Clinical outcomes were compared, stratified by
      assignment to angiographic follow-up or clinical follow-up alone. RESULTS:
      Compared with clinical follow-up alone, angiographic follow-up patients had a
      significantly higher rate of target vessel revascularization (TVR) at 1 year
      (adjusted hazard ratio [HR] 1.46; p = 0.04), with similar relative increases in
      PES and BMS patients. Because PES reduced TVR by approximately 60% regardless of
      type of follow-up, assignment to angiographic follow-up tended to overestimate
      the absolute benefit of PES relative to clinical follow-up alone. In contrast,
      assessment of end points immediately before the time of follow-up angiography led
      to substantial underestimation of the absolute benefit of PES implantation.
      CONCLUSIONS: Performance of mandatory angiographic follow-up increases rates of
      TVR among patients receiving both BMS and PES and overestimates the absolute
      clinical benefits of PES relative to clinical follow-up alone. Nonetheless, PES
      substantially reduces TVR regardless of assignment to mandatory angiographic
      follow-up or not. Future studies designed to determine the true clinical benefits
      of DES should either forgo routine angiographic follow-up or separate the time of
      repeat angiography from the primary clinical end point by as long as possible.

PMID- 16814646
TI  - The role of clopidogrel in early and sustained arterial patency after
      fibrinolysis for ST-segment elevation myocardial infarction: the ECG CLARITY-TIMI
      28 Study.
AB  - OBJECTIVES: This study was designed to determine the relationship between
      clopidogrel and early ST-segment resolution (STRes) and the interaction of the
      two with clinical outcomes after fibrinolysis. BACKGROUND: ST-segment resolution
      is an early noninvasive marker of coronary reperfusion. METHODS: The CLARITY-TIMI
      28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial
      Infarction 28) trial randomized 3,491 patients with ST-segment elevation
      myocardial infarction (STEMI) undergoing fibrinolysis to clopidogrel versus
      placebo. ST-segment resolution was defined as complete (>70%), partial (30% to
      70%), or none (<30%). RESULTS: Electrocardiograms were valid for interpretation
      in 2,431 patients at 90 min and 2,087 at 180 min. There was no difference in the
      rate of complete STRes between the clopidogrel and placebo groups at 90 min
      (38.4% vs. 36.6% at 90 min). When patients were stratified by STRes category,
      treatment with clopidogrel resulted in greater benefit among those with evidence
      of early STRes, with greater odds of an open artery at late angiography in
      patients with partial (odds ratio [OR] 1.4, p = 0.04) or complete (OR 2.0, p <
      0.001) STRes, but no improvement in those with no STRes at 90 min (OR 0.89, p =
      0.48) (p for interaction = 0.003). Clopidogrel was also associated with a
      significant reduction in the odds of an in-hospital death or myocardial
      infarction in patients who achieved partial (OR 0.30, p = 0.003) or complete
      STRes at 90 min (OR 0.49, p = 0.056), whereas clinical benefit was not apparent
      in patients who had no STRes (OR 0.98, p = 0.95) (p for interaction = 0.027). By
      30 days, the clinical benefit of clopidogrel was predominately seen in patients
      with complete STRes. CONCLUSIONS: Clopidogrel appears to improve late coronary
      patency and clinical outcomes by preventing reocclusion of open arteries rather
      than by facilitating early reperfusion.

PMID- 16814647
TI  - Atorvastatin increases plasma soluble Fms-like tyrosine kinase-1 and decreases
      vascular endothelial growth factor and placental growth factor in association
      with improvement of ventricular function in acute myocardial infarction.
AB  - OBJECTIVES: This study examined whether atorvastatin increases plasma levels of
      soluble Fms-like tyrosine kinase 1 (sFlt-1) and reciprocally decreases vascular
      endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in
      patients with acute myocardial infarction (AMI). BACKGROUND: Statins exert
      cardioprotective actions partly through anti-inflammatory actions. By capturing
      VEGF and PlGF in plasma, sFlt-1 acts as a natural inhibitor of VEGF and PlGF,
      which have proinflammatory properties. METHODS: Left ventriculography and enzyme
      linked immunosorbent assay of plasma levels of sFlt-1, VEGF, and PlGF were
      repeated after AMI in 50 consecutive patients with a first AMI. Patients were
      randomized to treatment with atorvastatin (10 mg/day; n=25) or placebo (n=25)
      within 3 days after AMI, and therapy was continued for 6 months. RESULTS: The
      sFlt-1 levels were low in the acute phase, followed by an increase at 2 weeks
      after AMI, whereas free VEGF and PlGF levels were high in the acute phase,
      followed by a decrease at 2 weeks. Atorvastatin increased sFlt-1 levels and
      reciprocally decreased VEGF and PlGF levels at 6 months compared with placebo.
      The increase in sFlt-1 levels and the decrease in VEGF and PlGF levels were
      correlated with improvement of left ventricular ejection fraction during the
      follow-up period. CONCLUSIONS: There was a reciprocal relationship between
      changes in sFlt-1 levels and changes in VEGF and PlGF levels after AMI; and
      atorvastatin increased sFlt-1 levels while decreasing VEGF and PlGF levels. These
      changes were associated with late improvement of post-MI ventricular function,
      and may represent an additional benefit of statin therapy.

PMID- 16814648
TI  - Determinants of coronary steal in chronic total coronary occlusions donor artery,
      collateral, and microvascular resistance.
AB  - OBJECTIVES: We aimed to assess the mechanisms of coronary steal by direct
      hemodynamic measurements of the collateral circulation in chronic total coronary
      occlusions (CTO). BACKGROUND: Coronary steal may cause ischemia despite well
      developed collaterals in coronary artery disease. METHODS: Fifty-six patients
      were studied during recanalization of a CTO. Before recanalization, the
      fractional flow reserve in the donor artery (FFR(D)) at the takeoff of the
      collaterals and the coronary flow reserve were recorded. After crossing the
      occlusion, the distal coronary flow velocity was measured by a Doppler wire
      (APV(Occl)), and distal pressure by a pressure wire. Changes of these parameters
      were assessed during intravenous adenosine (140 microg/kg/min). Resistance
      indexes for the donor artery (R(D)), collaterals (R(C)), and microcirculation
      (R(P)) were calculated. RESULTS: Adenosine caused a decrease of APV(Occl) (i.e.,
      coronary steal, in 26 patients [group S], an increase in 19 patients [group R],
      and no change in 11 patients). The FFR(D) was lower in group S. R(D) and R(C)
      increased in group S, while R(D) did not change significantly and R(C) decreased
      in group R. Patients with steal had more severe regional dysfunction. Patients
      with steal but without an FFR(D) <0.8 tended to have an impaired microvascular
      function. CONCLUSIONS: We could demonstrate that coronary steal in man is mainly
      due to a hemodynamically significant donor artery lesion, but can also occur due
      to an impaired vasodilatory reserve of the microcirculation in the absence of a
      donor artery lesion. Coronary steal may have an adverse influence on the
      preservation of myocardial function by collaterals.

PMID- 16814649
TI  - Rapid decline of collateral circulation increases susceptibility to myocardial
      ischemia: the trade-off of successful percutaneous recanalization of chronic
      total occlusions.
AB  - OBJECTIVES: We evaluated the time-behavior of changes in collateral circulation
      after successful percutaneous coronary intervention (PCI) with drug-eluting
      stents (DES) in chronic (>1 month) total occlusions (CTO), and assessed their
      relationship with myocardial ischemia. BACKGROUND: It has been hypothesized that
      the immediate reduction of collateral flow after PCI of CTO could expose the
      patients to a higher risk of future ischemic events in the case of vessel
      reocclusion. METHODS: In 42 patients with CTO, two consecutive balloon inflations
      and final DES deployment were performed after positioning of a pressure
      guidewire. Minimal lumen diameter (MLD), diameter stenosis (DS), angiographic
      collateral grading (Rentrop score), myocardial (FFRmyo), coronary (FFRcor), and
      collateral fractional flow reserve (FFRcoll) were evaluated. Chest pain and the
      sum of ST-segment elevation (SigmaST) were analyzed to document the occurrence
      and extent of myocardial ischemia. RESULTS: Percutaneous coronary intervention
      induced a progressive improvement of indexes of stenosis severity (MLD, DS,
      Thrombolysis in Myocardial Infarction flow, FFRmyo, and FFRcor) and a rapid
      reduction in collateral circulation (FFRcoll and Rentrop score). A progressive
      worsening of ischemia at each balloon inflation occurred, concomitant with the
      reduction of collateral circulation. At linear regression analysis, an inverse
      relationship of FFRcoll with SigmaST (R2 = 0.352, p < 0.001) and angina pain
      score (R(2) = 0.247, p < 0.001) was observed. CONCLUSIONS: In CTO, collateral
      circulation, which provides most coronary flow at baseline, rapidly declines
      after successful stent implantation and the restoration of an antegrade flow.
      This rapid de-recruitment of collaterals is likely to put such patients at risk
      of future ischemic events.

PMID- 16814650
TI  - Walking with Sir William. Reflections on collateral steal, recruitment, and
      ischemic protection.

PMID- 16814651
TI  - Decrease in circulating myeloid dendritic cell precursors in coronary artery
      disease.
AB  - OBJECTIVES: We analyzed the frequency of myeloid dendritic cell (mDC) and
      plasmacytoid dendritic cell (pDC) precursors in blood of patients with coronary
      artery disease (CAD) and in atherosclerotic carotid plaques of patients with
      cerebrovascular disease (CVD). BACKGROUND: Circulating DC precursors are reduced
      in several autoimmune diseases. Atherosclerosis has features of an autoimmune
      disease, such as the presence of autoantibodies or autoreactive T cells. Tissue
      resident DCs were previously described in atheromata, and it is assumed that they
      are important for the activation of T cells against autoantigens there. METHODS:
      Circulating mDC and pDC precursors were flow cytometrically detected in healthy
      controls (n = 19), CAD patients with stable (n = 20) and unstable angina pectoris
      (n = 19), and acute myocardial infarction (n = 17). In human carotid plaques (n =
      65), mDC and pDC precursors were identified immunohistochemically. RESULTS:
      Circulating mDC precursors were significantly reduced in patients with stable
      angina pectoris (0.19%, p = 0.04), unstable angina pectoris (0.16%, p = 0.004),
      and acute myocardial infarction (0.08%, p < 0.001) compared with control patients
      (0.22% of peripheral blood mononuclear cells). In contrast, pDC numbers were not
      significantly altered. Circulating mDC precursors inversely correlated with high
      sensitivity C-reactive protein (r = -0.38, p = 0.001) or interleukin-6 (r = 
      0.42, p < 0.001). In contrast to pDC, significantly more mDC precursors were
      observed in vulnerable carotid plaques (24, 0.25 mm2; n = 31; p = 0.003) than in
      stable ones (6.4, 0.25 mm2; n = 34). CONCLUSIONS: Similar to autoimmune diseases,
      circulating mDC precursors were significantly reduced in patients with CAD. The
      emergence of mDC precursors in vulnerable plaques suggests their recruitment into
      atheromata as a possible reason for their decrease in blood. In contrast, no
      significant association of circulating pDC precursors with atherosclerosis was
      observed.

PMID- 16814652
TI  - Diagnostic accuracy of optical coherence tomography and integrated backscatter
      intravascular ultrasound images for tissue characterization of human coronary
      plaques.
AB  - OBJECTIVES: The purpose of the present study was to validate the diagnostic
      accuracy of optical coherence tomography (OCT), integrated backscatter
      intravascular ultrasound (IB-IVUS), and conventional intravascular ultrasound (C
      IVUS) for tissue characterization of coronary plaques and to evaluate the
      advantages and limitations of each of these modalities. BACKGROUND: The
      diagnostic accuracy of OCT for characterizing tissue types is well established.
      However, comparisons among OCT, C-IVUS, and IB-IVUS have not been done. METHODS:
      We examined 128 coronary arterial sites (42 coronary arteries) from 17 cadavers;
      IVUS and OCT images were acquired on the same slice as histology. Ultrasound
      signals were obtained using an IVUS system with a 40-MHz catheter and digitized
      at 1 GHz with 8-bit resolution. The IB values of the ultrasound signals were
      calculated with a fast Fourier transform. RESULTS: Using histological images as a
      gold standard, the sensitivity of OCT for characterizing calcification, fibrosis,
      and lipid pool was 100%, 98%, and 95%, respectively. The specificity of OCT was
      100%, 94%, and 98%, respectively (Cohen's kappa = 0.92). The sensitivity of IB
      IVUS was 100%, 94%, and 84%, respectively. The specificity of IB-IVUS was 99%,
      84%, and 97%, respectively (Cohen's kappa = 0.80). The sensitivity of C-IVUS was
      100%, 93%, and 67%, respectively. The specificity of C-IVUS was 99%, 61%, and
      95%, respectively (Cohen's kappa = 0.59). CONCLUSIONS: Within the penetration
      depth of OCT, OCT has a best potential for tissue characterization of coronary
      plaques. Integrated backscatter IVUS has a better potential for characterizing
      fibrous lesions and lipid pools than C-IVUS.

PMID- 16814653
TI  - Alterations in the pattern of collagen deposition may contribute to the
      deterioration of systolic function in hypertensive patients with heart failure.
AB  - OBJECTIVES: We sought to assess the distribution of collagen deposits and
      collagen degradation in hypertensive patients with either systolic heart failure
      (SHF) or diastolic heart failure (DHF). BACKGROUND: Increased collagen synthesis
      and deposition have been described in the myocardium of heart failure (HF)
      hypertensive patients. METHODS: We studied 39 HF hypertensive patients subdivided
      into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were
      performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular
      and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1
      and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in
      cardiac samples by Western blot and immunohistochemistry, and in blood samples by
      enzyme-linked immunosorbent assay. RESULTS: Mysial CVF was lower in SHF
      hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive
      patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in
      the two groups of hypertensive patients than in normotensive subjects, and in SHF
      hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was
      increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group
      compared with the other two groups of subjects. The MMP-1 expression was
      increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive
      patients compared with DHF hypertensive and normotensive subjects. The serum MMP
      1:TIMP-1 ratio was inversely correlated with ejection fraction (r = -0.510, p <
      0.001) and directly correlated with left ventricular end-diastolic diameter (r =
      0.549, p < 0.001) in all subjects. CONCLUSIONS: These findings show that the
      pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are
      different in the myocardium of SHF and DHF hypertensive patients. It is proposed
      that excessive degradation of mysial collagen may be related to the compromise of
      systolic function in HF hypertensive patients.

PMID- 16814654
TI  - Extracellular matrix remodeling in hypertensive heart disease.

PMID- 16814655
TI  - Short-term change in distance walked in 6 min is an indicator of outcome in
      patients with chronic heart failure in clinical practice.
AB  - OBJECTIVES: The purpose of this study was to investigate the prognostic value of
      change in distance walked in 6 min in chronic heart failure (CHF). BACKGROUND:
      The strongest indication for the 6-min walking test (6MWT) is for measuring the
      response to therapeutic interventions in patients with CHF. Whether the increase
      in distance walked after a therapeutic intervention translates into improved
      clinical outcome is largely unknwon. METHODS: We studied 476 CHF patients with
      left ventricular systolic dysfunction who were referred to our institution for
      adjustment of heart failure therapy because of persisting or worsening symptoms.
      Adjustment of therapy involved four classes of drugs: angiotensin-converting
      enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, loop
      diuretics, and aldosterone antagonists. A standardized 6MWT was performed at
      baseline and at discharge. RESULTS: After 15.2 +/- 8 days, the distance walked
      increased from 326 +/- 107 m to 408 +/- 109 m (+25%; p = 0.001). During a mean
      follow-up of 23.9 months, 94 patients died and 12 patients underwent cardiac
      transplantation. Among a set of variables, New York Heart Association functional
      class (p = 0.02), serum creatinine concentration (p = 0.01), left ventricular
      ejection fraction (p = 0.002), distance walked at baseline (p = 0.0002), and
      change in distance walked (p = 0.002) were significant independent predictors of
      survival. When the patients were divided into two subgroups according to the
      median value of the distance walked at baseline, the increase in walking distance
      was significantly associated with survival only in the subgroup of patients who
      walked <340 m at baseline. CONCLUSIONS: Our data indicate that repeating a 6MWT
      after drug intervention provides independent prognostic information in CHF
      patients with more compromised exercise capacity.

PMID- 16814656
TI  - A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden
      death on chromosome 10q25-26.
AB  - OBJECTIVES: We sought to identify the genetic locus for an inherited form of
      dilated cardiomyopathy (DCM) that is characterized by diffuse myocardial fibrosis
      and sudden death. BACKGROUND: Genetic studies have mapped multiple loci for DCM,
      which is a major cause of nonischemic heart failure; however, the genes
      responsible for the majority of cases have yet to be identified. METHODS: Sixty
      six family members were evaluated by 12-lead electrocardiogram (ECG),
      echocardiogram, and laboratory studies. Individuals with echocardiographically
      documented DCM were defined as affected. Subjects were considered unaffected if
      they were older than 20 years of age, had a normal ECG and echocardiogram, no
      personal history of heart failure, and had no affected offspring. Genotyping was
      performed using polymorphic markers. RESULTS: Genome-wide linkage analysis
      identified a novel locus for this inherited phenotype on chromosome 10q25.3
      q26.13. Peak two-point logarithm of the odds scores >3.0 were obtained
      independently with each family using the markers D10S1773 and D10S1483,
      respectively. Haplotype analyses defined a critical interval of 14.0 centiMorgans
      between D10S1237 and D10S1723, corresponding to a physical distance of 9.5
      megabases. Multipoint linkage analyses confirmed this interval and generated a
      peak logarithm of the odds score of 8.2 indicating odds of >100,000,000:1 in
      favor of this interval as the location of the gene defect responsible for DCM in
      these families. CONCLUSIONS: We have mapped a novel locus for cardiomyopathy,
      diffuse myocardial fibrosis, and sudden death to chromosome 10q25-q26. The
      identification of the causative gene in this interval will be an important step
      in understanding the fundamental mechanisms of heart failure and sudden death.

PMID- 16814657
TI  - Cost-effectiveness of a microvolt T-wave alternans screening strategy for
      implantable cardioverter-defibrillator placement in the MADIT-II-eligible
      population.
AB  - OBJECTIVES: This study was designed to compare the cost-effectiveness of
      implantable cardioverter-defibrillator (ICD) placement with and without risk
      stratification with microvolt T-wave alternans (MTWA) testing in the MADIT-II
      (Second Multicenter Automatic Defibrillator Implantation Trial) eligible
      population. BACKGROUND: Implantable cardioverter-defibrillators have been shown
      to prevent mortality in the MADIT-II population. Microvolt T-wave alternans
      testing has been shown to be effective in risk stratifying MADIT-II-eligible
      patients. METHODS: On the basis of published data, cost-effectiveness of three
      therapeutic strategies in MADIT-II-eligible patients was assessed using a Markov
      model: 1) ICD placement in all; 2) ICD placement in patients testing MTWA non
      negative;, and 3) medical management. Outcomes of expected cost, quality-adjusted
      life-years (QALYs), and incremental cost-effectiveness were determined for
      patient lifetime. RESULTS: Under base-case assumptions, providing ICDs only to
      those who test MTWA non-negative produced a gain of 1.14 QALYs at an incremental
      cost of 55,700 dollars when compared to medical therapy, resulting in an
      incremental cost-effectiveness ratio (ICER) of 48,700 dollars/QALY. When compared
      with a MTWA risk-stratification strategy, placing ICDs in all patients resulted
      in an ICER of 88,700 dollars/QALY. Most (83%) of the potential benefit was
      achieved by implanting ICDs in the 67% of patients who tested MTWA non-negative.
      Results were most sensitive to the effectiveness of MTWA as a risk-stratification
      tool, MTWA negative screen rate, cost and efficacy of ICD therapy, and patient
      risk for arrhythmic death. CONCLUSIONS: Risk stratification with MTWA testing in
      MADIT-II-eligible patients improves the cost-effectiveness of ICDs. Implanting
      defibrillators in all MADIT-II-eligible patients, however, is not cost-effective,
      with one-third of patients deriving little additional benefit at great expense.

PMID- 16814658
TI  - Focal atrial tachycardia originating from the non-coronary aortic sinus:
      electrophysiological characteristics and catheter ablation.
AB  - OBJECTIVES: We sought to investigate electrophysiological characteristics and
      catheter ablation in patients with focal atrial tachycardia (AT) originating from
      the non-coronary aortic sinus (AS). BACKGROUND: In patients with failed ablation
      of focal AT near the His bundle (HB) region, an origin from the non-coronary AS
      should be considered because of the close anatomical relationship. METHODS: This
      study included 9 patients with focal AT, in 6 of whom attempted radiofrequency
      (RF) ablation had previously failed. Activation mapping was performed during
      tachycardia to identify an earliest activation in the atria and the AS. The
      aortic root angiography was performed to identify the origin in the AS before RF
      ablation. RESULTS: Focal AT was reproducibly induced by atrial pacing. Mapping in
      atria demonstrated that the earliest atrial activation was located at the HB
      region, whereas mapping in the non-coronary AS demonstrated that an earliest
      atrial activation preceded the atrial activation at the HB by 12.2 +/- 6.9 ms and
      was anatomically located superoposterior to the HB in all 9 patients. Also, His
      potentials were not found at the successful site in the non-coronary AS in all 9
      patients. The focal AT was terminated in <8 s in all 9 patients. Junctional beats
      and PR prolongation did not occur during RF application in all 9 patients. No
      complications occurred in any of the nine patients. All 9 patients were free of
      arrhythmias without antiarrhythmic drugs during a follow-up of 9 +/- 3 months.
      CONCLUSIONS: In patients with focal AT near the HB region, mapping in the non
      coronary AS can improve clinical outcome.

PMID- 16814659
TI  - Autonomic innervation and segmental muscular disconnections at the human
      pulmonary vein-atrial junction: implications for catheter ablation of atrial
      pulmonary vein junction.
AB  - OBJECTIVES: This study sought to examine the muscle connections and autonomic
      nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.
      BACKGROUND: One approach to catheter ablation of atrial fibrillation (AF) is to
      isolate PV muscle sleeves from the LA. Elimination of vagal response further
      improves success rates. METHODS: We performed immunohistochemical staining on 192
      circumferential venoatrial segments (32 veins) harvested from 8 autopsied human
      hearts using antibodies to tyrosine hydroxylase (TH) and choline
      acetyltransferase (ChAT). RESULTS: Muscular discontinuities of widths 0.1 to 5.5
      mm (1.1 +/- 1.0 mm) and abrupt 90 degrees changes in fiber orientation were found
      in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although
      these anisotropic features were more common in the anterosuperior junction (p <
      0.01), they were also present around the entire PV-LA junction. Autonomic nerve
      density was highest in the anterosuperior segments of both superior veins (p <
      0.05 versus posteroinferior) and inferior segments of both inferior veins (p <
      0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p <
      0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and
      cholinergic nerves were highly co-located at tissue and cellular levels. A
      significant proportion (30%) of ganglion cells expressed dual adrenocholinergic
      phenotypes. CONCLUSIONS: Muscular discontinuities and abrupt fiber orientation
      changes are present in >50% of PV-LA segments, creating significant substrates
      for re-entry. Adrenergic and cholinergic nerves have highest densities within 5
      mm of the PV-LA junction, but are highly co-located, indicating that it is
      impossible to selectively target either vagal or sympathetic nerves during
      ablation procedures.

PMID- 16814660
TI  - Multislice computed tomography and magnetic resonance imaging for the assessment
      of reperfused acute myocardial infarction.
AB  - OBJECTIVES: We evaluated the accuracy of in vivo delayed-enhancement multislice
      computed tomography (DE-MSCT) and delayed-enhancement magnetic resonance imaging
      (DE-MRI) for the assessment of myocardial infarct size using postmortem
      triphenyltetrazolium chloride (TTC) pathology as standard of reference.
      BACKGROUND: The diagnostic value of DE-MSCT for the assessment of acute
      reperfused myocardial infarction is currently unclear. METHODS: In 10 domestic
      pigs (25 to 30 kg), the circumflex coronary artery was balloon-occluded for 2 h
      followed by reperfusion. After 5 days (3 to 7 days), DE-MRI (1.5-T) was performed
      15 min after administration of 0.2 mmol/kg gadolinium-DTPA using an inversion
      recovery gradient echo technique. On the same day, DE-MSCT (64-slice) was
      performed 15 min after administration of 1 gI/kg of iodinated contrast material.
      One day after imaging, hearts were excised, sectioned in 8 mm short-axis slices,
      and stained with TTC. Infarct size was defined as the hyperenhanced area on DE
      MSCT and DE-MRI images and the TTC-negative area on TTC pathology slices. Infarct
      size was expressed as percentage of total slice area. RESULTS: Infarct size
      determined by DE-MSCT and DE-MRI showed a good correlation with infarct size
      assessed with TTC pathology (R2 = 0.96 [p < 0.001] and R(2) = 0.93 [p < 0.001],
      respectively). The correlation between DE-MSCT and DE-MRI was also good (R2 =
      0.96; p < 0.001). The relative difference in CT attenuation value of infarcted
      myocardium compared to remote myocardium was 191 +/- 18%. The relative MR signal
      intensity between infarcted myocardium and remote myocardium was 554 +/- 156%.
      CONCLUSIONS: We demonstrated that DE-MSCT can assess acute reperfused myocardial
      infarction in good agreement with in vivo DE-MRI and TTC pathology.

PMID- 16814661
TI  - Multidetector computed tomography myocardial perfusion imaging during adenosine
      stress.
AB  - OBJECTIVES: The purpose of this study is to validate the accuracy of
      multidetector computed tomography (MDCT) to measure differences in regional
      myocardial perfusion during adenosine stress in a canine model of left anterior
      descending (LAD) artery stenosis, during first-pass, contrast-enhanced helical
      MDCT. BACKGROUND: Myocardial perfusion imaging by MDCT may have significant
      implications in the diagnosis and treatment of coronary artery disease. METHODS:
      Eight dogs were prepared with a LAD stenosis, and contrast-enhanced MDCT imaging
      was performed 5 min into adenosine infusion (0.14 to 0.21 mg/kg/min). Images were
      analyzed using a semiautomated approach to define the regional signal density
      (SD) ratio (myocardial SD/left ventricular blood pool SD) in stenosed and remote
      territories, and then compared with microsphere myocardial blood flow (MBF)
      measurements. RESULTS: Mean MBF in stenosed versus remote territories was 1.37 +/
      0.46 ml/g/min and 1.29 +/- 0.48 ml/g/min at baseline (p = NS) and 2.54 +/- 0.93
      ml/g/min and 8.94 +/- 5.74 ml/g/min during adenosine infusion, respectively (p <
      0.05). Myocardial SD was 92.3 +/- 39.5 HU in stenosed versus 180.4 +/- 41.9 HU in
      remote territories (p < 0.001). There was a significant linear association of the
      SD ratio with MBF in the stenosed territory (R = 0.98, p = 0.001) and between
      regional myocardial SD ratio and MBF <8 ml/g/min, slope = 0.035, SE = 0.007, p <
      0.0001. Overall, there was a significant non-linear relationship over the range
      of flows studied (LR chi-square [2 degrees of freedom] = 31.8, p < 0.0001).
      CONCLUSIONS: Adenosine-augmented MDCT myocardial perfusion imaging provides
      semiquantitative measurements of myocardial perfusion during first-pass MDCT
      imaging in a canine model of LAD stenosis.

PMID- 16814662
TI  - Interventional atrial septal defect closure using a totally bioresorbable
      occluder matrix: development and preclinical evaluation of the BioSTAR device.
AB  - OBJECTIVES: We sought to test the hypothesis that interventional atrial septal
      defect (ASD) closure can be performed safely and effectively using a
      bioresorbable occluder matrix. BACKGROUND: The ideal septal occluder scaffold
      should promote the healthiest and most complete healing response while eventually
      facilitating the full resorption of the material and leaving "native" tissue
      behind, thus minimizing the potential for future complications from chronic
      foreign body and maintaining the possibility for later unobstructed transseptal
      access to the left atrium. METHODS: The STARFlex occluders (NMT Medical Inc.,
      Boston, Massachusetts) were modified by substituting the conventional polyester
      fabric for a bioengineered, acellular type-I collagen matrix derived from porcine
      submucosa with a heparin-coated surface (BioSTAR occluder, NMT Medical Inc.).
      Comparative transcatheter closure of ASDs was performed in young sheep (n = 36).
      Gross pathology and histopathology were obtained after follow-up periods ranging
      from 7 days to 2 years. RESULTS: The STARFlex (control) devices were encapsulated
      time-dependently by ingrown fibrous tissue. Histology showed a mild but
      chronically persisting foreign body reaction. By contrast, BioSTAR devices
      exhibited a mild-to-moderate transient cellular immune response. Heparin coating
      of the BioSTAR surface improved the biocompatibility of the device by reducing
      surface thrombogencity. A remodeling process of the collagen scaffold, starting
      after 30 days in vivo, resulted in the full replacement of the matrix by host
      tissue after 2 years of follow-up. CONCLUSIONS: The BioSTAR device is the first
      septal occluder with a totally bioresorbable matrix that is fully replaced by
      host tissue during the healing process. The promising results of this study
      support testing of the BioSTAR device in clinical trials.

PMID- 16814663
TI  - Metyrapone improves endothelial dysfunction in patients with treated depression.
AB  - OBJECTIVES: This study sought to examine the effect of metyrapone on endothelial
      dysfunction in patients with treated recurrent major depression. BACKGROUND:
      Depression is an independent risk factor for the development of coronary heart
      disease, and patients with depression have endothelial dysfunction, an
      atherogenic abnormality. This abnormality may be attributable to abnormal
      hypothalamic-pituitary-adrenal (HPA) axis function, a feature of depression,
      resulting in increased exposure to cortisol. Cortisol administration produces
      endothelial dysfunction in healthy subjects. METHODS: We measured endothelial
      function using flow-mediated dilation (FMD) of the brachial artery in 30 patients
      with depression and in 36 matched control subjects. Patients were randomized
      (double blind) to metyrapone (an inhibitor of cortisol synthesis) or placebo, and
      FMD was remeasured 6 h later. RESULTS: At baseline, FMD was impaired in patients
      versus control subjects (mean [standard error]), -1.27% [0.91%] vs. 4.37% [0.59%]
      (p < 0.001). The FMD was similar in the placebo and the metyrapone patient groups
      at baseline (0.17% [1.04%] vs. -2.72% [1.30%], p = 0.11). Metyrapone
      significantly reduced plasma cortisol levels. There was a significant improvement
      in FMD in the metyrapone group from -2.72% [1.30%] to 3.82% [0.99%] (p < 0.001),
      whereas the change in the placebo group, from 0.17% [1.04%] to 1.15% [1.14%], was
      not significant. Analysis of covariation showed that the effect of metyrapone was
      significant (p = 0.034). CONCLUSIONS: Inhibition of cortisol production by
      metyrapone ameliorates the endothelial dysfunction seen in depression, suggesting
      that the mechanism of the endothelial dysfunction may involve cortisol.

PMID- 16814664
TI  - Erythropoietin enhances neovascularization of ischemic myocardium and improves
      left ventricular dysfunction after myocardial infarction in dogs.
AB  - OBJECTIVES: We investigated the effects of erythropoietin (EPO) on
      neovascularization and cardiac function after myocardial infarction (MI).
      BACKGROUND: Erythropoietin exerts antiapoptotic effects and mobilizes endothelial
      progenitor cells (EPCs). METHODS: We intravenously administered EPO (1,000 IU/kg)
      immediately [EPO(0) group], 6 h [EPO(6h) group], or 1 week [EPO(1wk) group] after
      the permanent ligation of the coronary artery in dogs. Control animals received
      saline immediately after the ligation. RESULTS: The infarct size 6 h after MI was
      significantly smaller in the EPO(0) group than in the control group (61.5 +/-
      6.0% vs. 22.9 +/- 2.2%). One week after MI, the circulating CD34-positive
      mononuclear cell numbers in both the EPO(0) and the EPO(6h) groups were
      significantly higher than in the control group. In the ischemic region, the
      capillary density and myocardial blood flow 4 weeks after MI was significantly
      higher in both the EPO(0) and the EPO(6h) groups than in the control group. Four
      weeks after MI, left ventricular (LV) ejection fraction in the EPO(6h) (48.6 +/-
      1.9%) group was significantly higher than that in either the control (41.9 +/-
      0.9%) or the EPO(1wk) (42.6 +/- 1.2%) group but significantly lower than that in
      the EPO(0) group (56.1 +/- 2.3%). The LV end-diastolic pressure 4 weeks after MI
      in both the EPO(0) and the EPO(6h) groups was significantly lower than either the
      control or the EPO(1wk) group. Hematologic parameters did not differ among the
      groups. CONCLUSIONS: In addition to its acute infarct size-limiting effect, EPO
      enhances neovascularization, likely via EPC mobilization, and improves cardiac
      dysfunction in the chronic phase, although it has time-window limitations.

PMID- 16814665
TI  - Erythropoietin: repair of the failing heart.

PMID- 16814666
TI  - Meeting highlights of the 9th annual scientific sessions of the society for
      cardiovascular magnetic resonance: Miami, Florida, January 20-22, 2006.

PMID- 16814667
TI  - Pathology of drug-eluting stents in humans: delayed healing and late thrombotic
      risk.
AB  - OBJECTIVES: This study examined human drug-eluting stents (DES) to determine the
      long-term effects of these stents on coronary arterial healing and identified
      mechanisms underlying late stent thrombosis (LST). BACKGROUND: Although DES
      reduce the need for repeat revascularization compared with bare-metal stents
      (BMS), data suggest the window of thrombotic risk for Cypher (Cordis Corp., Miami
      Lakes, Florida) and Taxus (Boston Scientific Corp., Natick, Massachusetts) DES
      extends far beyond that for BMS. METHODS: From a registry of 40 autopsies of DES
      (68 stents), 23 DES cases of >30 days duration were compared with 25 matched
      autopsies of BMS implantation. Late stent thrombosis was defined as an acute
      thrombus within a stent >30 days old. RESULTS: Of 23 patients with DES >30 days
      old, 14 had evidence of LST. Cypher and Taxus DES showed greater delayed healing
      characterized by persistent fibrin deposition (fibrin score 2.3 +/- 1.1 vs. 0.9
      +/- 0.8, p = 0.0001) and poorer endothelialization (55.8 +/- 26.5%) compared with
      BMS (89.8 +/- 20.9, p = 0.0001). Moreover, DES with LST showed more delayed
      healing compared with patent DES. In 5 of 14 patients suffering LST, antiplatelet
      therapy had been withdrawn. Additional procedural and pathologic risk factors for
      LST were: 1) local hypersensitivity reaction; 2) ostial and/or bifurcation
      stenting; 3) malapposition/incomplete apposition; 4) restenosis; and 5) strut
      penetration into a necrotic core. CONCLUSIONS: The Cypher and Taxus DES result in
      delayed arterial healing when compared with BMS of similar implant duration. The
      cause of DES LST is multifactorial with delayed healing in combination with other
      clinical and procedural risk factors playing a role.

PMID- 16814668
TI  - Drug-eluting stent thrombosis: increasingly recognized but too frequently
      overemphasized.

PMID- 16814670
TI  - Moving preconditioning from bench to bedside.

PMID- 16814669
TI  - Post-reperfusion myocardial infarction: long-term survival improvement using
      adenosine regulation with acadesine.
AB  - OBJECTIVES: The purpose of this study was to assess the safety and efficacy of
      the adenosine regulating agent (ARA) acadesine for reducing long-term mortality
      among patients with post-reperfusion myocardial infarction (MI). BACKGROUND: No
      prospectively applied therapy exists that improves long-term survival after MI
      associated with coronary artery bypass graft (CABG) surgery-a robust model of
      ischemia/reperfusion injury. Pretreatment with the purine nucleoside autocoid
      adenosine mitigates the extent of post-ischemic reperfusion injury in animal
      models. Therefore, we questioned whether use of the ARA acadesine-by increasing
      interstitial adenosine concentrations in ischemic tissue-would improve long-term
      survival after post-reperfusion MI. METHODS: At 54 institutions, 2,698 patients
      undergoing CABG surgery were randomized to receive placebo (n = 1,346) or
      acadesine (n = 1,352) by intravenous infusion (0.1 mg/kg/min; 7 h) and in
      cardioplegia solution (placebo or acadesine; 5 microg/ml). Myocardial infarction
      was prospectively defined as: 1) new Q-wave and MB isoform of creatine kinase (CK
      MB) elevation (daily electrocardiography; 16 serial CK-MB measurements); or 2)
      autopsy evidence. Vital status was assessed over 2 years, and outcomes were
      adjudicated centrally. RESULTS: Perioperative MI occurred in 100 patients (3.7%),
      conferring a 4.2-fold increase in 2-year mortality (p < 0.001) compared with
      those not suffering MI. Acadesine treatment, however, reduced that mortality by
      4.3-fold, from 27.8% (15 of 54; placebo) to 6.5% (3 of 46; acadesine) (p =
      0.006), with the principal benefit occurring over the first 30 days after MI. The
      acadesine benefit was similar among diverse subsets, and multivariable analysis
      confirmed these findings. CONCLUSIONS: Acadesine is the first therapy proven to
      be effective for reducing the severity of acute post-reperfusion MI,
      substantially reducing the risk of dying over the 2 years after infarction.

PMID- 16814671
TI  - President's page: the rapid emergence of multi-modality cardiovascular imaging.

PMID- 16814672
TI  - Mesenchymal stem cells repair conduction block.

PMID- 16814674
TI  - Accuracy of noninvasive coronary angiography using computed tomography.

PMID- 16814676
TI  - The other face of the medal: the risks of exercise training.

PMID- 16814678
TI  - Pediatric cardiac critical care patients should be cared for by intensivists.

PMID- 16814680
TI  - Diagnosis and management of chronic heart failure.

PMID- 16814681
TI  - China's role in international cardiology.

PMID- 16814683
TI  - Renal artery stenting following unsuccessful balloon angioplasty.

PMID- 16814684
TI  - Sickle cell disease related pain: crisis and conflict.

PMID- 16814685
TI  - Coping, pain severity, interference, and disability: the potential mediating and
      moderating roles of race and education.
AB  - Researchers have demonstrated that certain types of pain coping are correlated
      with less pain severity and disability and that there are differences between
      Caucasians and African-American pain patients in their use of specific coping
      strategies. However, the extent to which racial group differences exist in the
      associations between pain coping strategies and pain severity, interference, and
      disability is unclear. Furthermore, the role of education in these associations
      is uncertain. We recruited a diverse community sample of individuals with chronic
      pain and their spouses to examine this issue (N = 105). Participants completed
      the Coping Strategies Questionnaire, Multidimensional Pain Inventory, and
      Sickness Impact Profile. Results showed that African-American participants
      reported significantly more pain severity, interference, and disability and
      reported using diverting attention and prayer and hoping pain-coping strategies
      significantly more often than Caucasian participants; however, only the racial
      group difference in prayer and hoping remained when controlling for education. We
      also examined whether race and education interacted with coping strategies in
      relating to pain and disability. Significant three-way interactions were found
      for physical and psychosocial disability, suggesting that educational level
      should be included in analyses exploring racial group differences. The results
      suggest the need for pain treatments that take into account the educational and
      cultural context of pain. PERSPECTIVE: This article demonstrates that demographic
      variables such as race and education should be considered together when
      evaluating the effectiveness of coping with pain. The findings have the potential
      to enhance research and clinical practice with diverse groups.

PMID- 16814686
TI  - Neonatal urinary bladder inflammation produces adult bladder hypersensitivity.
AB  - Inflammatory events experienced during early development may permanently alter
      sensory processing. Because urinary tract infections frequently occur during
      early development in females and painful bladder disorders have a high female
      prevalence, the present studies were undertaken to determine whether inflammation
      of the bladder in female rats could lead to altered sensory processing later in
      life. Female rat pups were anesthetized and treated as neonates (14th-16th days
      of life) or as adolescents (28th-30th days of life) with either intravesical
      zymosan (yeast cell wall component that produces robust inflammation),
      intravesical normal saline, or only with anesthesia. As adults, rats that had
      their bladders inflamed as neonates exhibited increased spontaneous micturition
      frequency and, after reinflammation of the bladder, increased cardiovascular and
      abdominal muscle contractile responses to urinary bladder distension when
      compared with controls. Similar effects were not observed in rats which did not
      experience inflammation of the bladder until adolescence. Evan's blue
      extravasation, a measure of the magnitude of inflammatory changes, was also
      greater in rats treated as neonates with intravesical zymosan. Thermal and
      mechanical hindpaw sensitivity was not altered by bladder inflammation.
      Altogether, this suggests that neonatal bladder inflammation increases bladder
      sensitivity and may be a cause of the hypersensitivity of painful bladder
      syndromes. PERSPECTIVE: The present study observed that bladder inflammation
      experienced in a neonatal rat led to accentuated responses to urinary bladder
      distension when tested as adults. This suggests that events experienced during
      development may permanently sensitize visceral sensory systems and so represent
      one of the causes of painful bladder disorders.

PMID- 16814687
TI  - Intensity dependence of auditory-evoked cortical potentials in fibromyalgia
      patients: a test of the generalized hypervigilance hypothesis.
AB  - On the basis of recent evidence concerning the amplification of incoming
      stimulation in fibromyalgia (FM) patients, it has been proposed that a
      generalized hypervigilance of painful and nonpainful sensations may be at the
      root of this disorder. So far, research into this issue has been inconclusive,
      possibly owing to the lack of agreement as to the operational definition of
      "generalized hypervigilance" and to the lack of robust objective measures
      characterizing the sensory style of FM patients. In this study, we recorded
      auditory-evoked potentials (AEPs) elicited by tones of increasing intensity (60,
      70, 80, 90, and 105 dB) in 27 female FM patients and 25 healthy controls.
      Fibromyalgia patients presented shorter N1 and P2 latencies and a stronger
      intensity dependence of their AEPs. Both results suggest that FM patients may be
      hypervigilant to sensory stimuli, especially when very loud tones are used. The
      most noteworthy difference between patients and control subjects is at the
      highest stimulus intensity, for which far more patients maintained increased N1
      P2 amplitudes in relation to the 90-dB tones. The larger AEP amplitudes to the
      105-dB tones suggest that defects in an inhibitory system protecting against
      overstimulation may be a crucial factor in the pathophysiology of FM. Because a
      stronger loudness dependence of AEPs has been related to weak serotonergic
      transmission, it is hypothesized that for many FM patients deficient inhibition
      of the response to noxious and intense auditory stimuli may be due to a
      serotonergic deficit. PERSPECTIVE: The study of auditory-evoked potentials in
      response to tones of increasing intensity in FM patients may help to clarify the
      pathophysiology of this disorder, especially regarding the role of inhibition
      deficits involving serotonergic dysfunction, and may be a useful tool to guide
      the pharmacologic treatment of FM patients.

PMID- 16814688
TI  - The effects of pH on beta-endorphin and morphine inhibition of calcium transients
      in dorsal root ganglion neurons.
AB  - During inflammation, immune cells migrate into inflamed tissue and release opioid
      peptides that activate opioid receptors on peripheral sensory neurons to reduce
      pain. A characteristic of the inflamed environment in which these opioids act is
      acidic pH. Activation of opioid receptors leads to a decrease in the calcium
      component of neuronal action potentials. We investigated the hypothesis that
      inhibitory effects of opioids on intracellular calcium transients in dorsal root
      ganglion neuronal cultures are potentiated at acidic extracellular pH.
      Intracellular calcium responses to stimulation with capsaicin were measured in
      untreated neurons or after preincubation with beta-endorphin or morphine. beta
      Endorphin significantly inhibited calcium responses to 300 nmol/L capsaicin at
      the lowest experimental extracellular pH (6.1, 6.5, and 7.2), whereas morphine
      inhibited capsaicin (300 nmol/L) responses significantly at pH 6.1 with a trend
      of inhibition at pH 6.5. The effect of pH on morphine inhibition of K+ -evoked
      calcium responses was also assessed. Morphine inhibition of calcium responses was
      significantly enhanced at pH 6.8 compared with pH 7.2 and pH 7.6. The inhibitory
      effects were reversed by naloxone, an opioid receptor antagonist. In conclusion,
      low extracellular pH potentiated beta-endorphin and morphine inhibition of
      calcium transients and might contribute to improved opioid efficacy during
      inflammation. PERSPECTIVE: The results of the current study suggest that acidic
      pH might contribute to increased opioid efficacy in inflamed tissue. This
      highlights the therapeutic potential of endogenous opioid analgesia, whereby
      opioid peptides are delivered locally in inflamed tissues, as well as the use of
      locally applied opioids in inflammatory conditions.

PMID- 16814689
TI  - Bee venom injection significantly reduces nociceptive behavior in the mouse
      formalin test via capsaicin-insensitive afferents.
AB  - Peripheral bee venom (BV) administration produces 2 contrasting effects,
      nociception and antinociception. This study was designed to evaluate whether the
      initial nociceptive effect induced by BV injection into the Zusanli acupoint is
      involved in producing the more prolonged antinociceptive effect observed in the
      mouse formalin test, and whether capsaicin-sensitive primary afferents are
      involved in these effects. BV injection into the Zusanli point increased spinal
      Fos expression but not spontaneous nociceptive behavior. BV pretreatment 10
      minutes before intraplantar formalin injection dose-dependently attenuated
      nociceptive behavior associated with the second phase of the formalin test. The
      destruction of capsaicin-sensitive primary afferents by resiniferatoxin (RTX)
      pretreatment selectively decreased BV-induced spinal Fos expression but did not
      affect BV-induced antinociception. Furthermore, BV injection increased Fos
      expression in tyrosine hydroxylase immunoreactive neurons in the locus caeruleus,
      and this expression was unaltered by RTX pretreatment. Finally, BV's
      antinociception was blocked by intrathecal injection of 10 microg idazoxan, and
      this effect was not modified by RTX pretreatment. These findings suggest that
      subcutaneous BV stimulation of the Zusanli point activates central
      catecholaminergic neurons via capsaicin-insensitive afferent fibers without
      induction of nociceptive behavior. This in turn leads to the activation of spinal
      alpha2-adrenoceptors, which ultimately reduces formalin-evoked nociceptive
      behaviors. PERSPECTIVE: This study demonstrates that BV acupuncture produces a
      significant antinociception without nociceptive behavior in rodents, which is
      mediated by capsaicin-insensitive afferents and involves activation of central
      adrenergic circuits. These results further suggest that BV stimulation into this
      acupuncture point might be a valuable alternative to traditional electrical or
      mechanical acupoint stimulation.

PMID- 16814690
TI  - Differential blockade of nerve injury-induced shift in weight bearing and thermal
      and tactile hypersensitivity by milnacipran.
AB  - Antidepressants such as tricyclic antidepressants have become used to treat a
      variety of chronic pain conditions. However, the side effects are dose-limiting
      in the treatment of chronic pain. Milnacipran is a norepinephrine/serotonin
      reuptake inhibitor that does not have the severe side effects associated with
      traditional tricyclic antidepressants. The effects of intrathecal and systemic
      administration of milnacipran on spinal nerve ligation (SNL)-induced thermal and
      mechanical hypersensitivity and shift in weight bearing were determined.
      Intrathecal administration of milnacipran was found to reverse both SNL-induced
      thermal and tactile (to von Frey filaments) hypersensitivity, as well as shift in
      weight bearing. Acute systemic administration of milnacipran also reversed nerve
      injury-induced thermal hypersensitivity for up to 5 hours but failed to reverse
      tactile hypersensitivity or shift in weight bearing. Of note, both intrathecal
      and subcutaneous administration of milnacipran induced thermal antinociception in
      both SNL and sham rats. Chronic (daily) systemic administration of milnacipran
      alleviated both thermal hypersensitivity and shift in weight bearing, with both
      acute and chronic effects observed on thermal hypersensitivity. However, chronic
      systemic milnacipran administration failed to alleviate tactile hypersensitivity
      to von Frey filaments. These results indicate that different mechanisms underlie
      shift in weight bearing, thermal hypersensitivity, and tactile hypersensitivity.
      PERSPECTIVE: These results indicate that the ability of milnacipran to relieve
      nerve injury-induced allodynia, hyperalgesia, and shift in weight bearing depends
      on the route of administration and the duration of treatment, with alleviation of
      SNL-induced tactile hypersensitivity and shift in weight bearing as a result of
      activity within the central-rather than the peripheral-nervous system.

PMID- 16814691
TI  - Comparison of clinical and evoked pain measures in fibromyalgia.
AB  - Evoked pain measures such as tender point count and dolorimetry are often used to
      determine tenderness in studies of fibromyalgia (FM). However, these measures
      frequently do not improve in clinical trials and are known to be influenced by
      factors other than pain such as distress and expectancy. The purpose of this
      investigation was to determine whether evoked pain paradigms that present
      pressure stimuli in a random fashion (eg, Multiple Random Staircase [MRS]) would
      track with clinical pain improvement in patients with FM better than traditional
      measures. Sixty-five subjects enrolled in a randomized clinical trial of
      acupuncture were observed longitudinally. Clinical pain was measured on a 101
      point numerical rating scale (NRS) and the Short Form McGill Pain Questionnaire
      (SF-MPQ), whereas evoked pressure sensitivity was assessed via manual tender
      point count, dolorimetry, and MRS methods. Improvements in clinical pain and
      evoked pain were assessed irrespective of group assignment. Improvement was seen
      in clinical pain during the course of the trial as measured by both NRS (P =
      .032) and SF-MPQ (P = .001). The MRS was the only evoked pain measure to improve
      correspondingly with treatment (MRS, P = .001; tender point count and
      dolorimeter, P > .05). MRS change scores were correlated with changes in NRS pain
      ratings (P = .003); however, this association was not stronger than tender point
      or dolorimetry correlations with clinical pain improvement (P > .05). Pain
      sensitivity as assessed by random paradigms was associated with improvements in
      clinical FM pain. Sophisticated pain testing paradigms might be responsive to
      change in clinical trials. PERSPECTIVE: Trials in fibromyalgia often use both
      clinical and experimental methods of pain assessment; however, these two outcomes
      are often poorly correlated. We explore the relationship between changes in
      clinical and experimental pain within FM patients. Pressure pain testing that
      applies stimuli in a random order is associated with improvements in clinical
      pain, but this association was not stronger than other experimental techniques.

PMID- 16814694
TI  - Alcohol use disorders: a clinical update.
AB  - Alcohol use disorders are a significant public health problem. All providers who
      work with teenagers are likely to encounter youth for whom this is a relevant
      concern. Routine screening for alcohol use disorders has become the standard of
      care, and a number of validated, concise screening measures are now available.
      Youth with alcohol use disorders are unlikely to show the physical stigmata of
      adult alcohol dependence. Knowledge of risk variables can inform anticipatory
      guidance and interventions, and all providers can play a helpful role to address
      problematic use of alcohol.

PMID- 16814695
TI  - Adolescent abuse of other drugs.
AB  - This article provides a general overview of other drugs of abuse within the
      adolescent population. Stimulants, hallucinogens, club drugs, inhalants, sedative
      hypnotics, tranquilizers, opiates, and ergogenic drugs are included.
      Epidemiology, pharmacology, clinical aspects, laboratory, and treatment issues
      are addressed. Attention is focused on most commonly used drugs or representative
      drugs within each category. Review of alcohol, marijuana, and tobacco abuse can
      be found in other articles.

PMID- 16814696
TI  - Adolescent use and misuse of marijuana.
AB  - Substance use by adolescents and young adults continues to be a serious problem.
      Marijuana remains the most commonly used illicit substance with close to 50% of
      high school seniors admitting use at some time. Each year 2.6 million individuals
      in this country become new users and most are under 19 years old. Individuals who
      provide health care services to this age group must have an understanding of the
      drug, its pharmacokinetics, and the many short- and long-term adverse effects.
      Familiarity with risk factors associated with initiating use can be helpful in
      screening older children and targeting anticipatory guidance toward those most
      likely to benefit. This article reviews these issues and includes commentary on a
      recently published review of treatment programs.

PMID- 16814697
TI  - Risk factors and prevention in adolescent substance abuse: a biopsychosocial
      approach.
AB  - This article provides an overview of existing evidence regarding risk and
      prevention factors in adolescent substance abuse from a biopsychosocial
      viewpoint. It is believed that this approach offers a practical model for the
      integration of inherently complex factors into the clinical setting. These
      factors cannot be isolated from the influences of the greater society, such as
      the school system or homelessness. Prevention and treatment issues must approach
      the impaired adolescent with a multifactorial and comprehensive plan that
      integrates multidisciplinary involvement.

PMID- 16814698
TI  - Medical management of adolescent drug overdoses.
AB  - This article outlines the current clinical approach to poisonings in the
      adolescent age group. Management issues are presented for several specific
      substances frequently abused by this population. The purpose of such a review is
      to stimulate self-education in the practitioner. A secondary goal is to promote
      awareness of the various manifestations of substance abuse problems to facilitate
      recognition and referral. Adolescence is often a critical point for effective
      intervention and prevention on the road from use to addiction. Long-term survival
      may depend more on substance use rehabilitation than on the initial medical
      management.

PMID- 16814699
TI  - Adolescent tobacco use and dependence: assessment and treatment strategies.
AB  - Tobacco use is common among children and adolescents, and about 50% who try
      smoking will progress to regular use and dependence. Tobacco dependence is best
      conceptualized as a pediatric disease that should be addressed in adolescence.
      This article focuses on tobacco dependence, assessment and treatment, including
      goals of abstinence and exposure reduction. Although more research is needed,
      treatment success is more likely to occur with multicomponent interventions that
      are tailored to the individual needs and the unique issues for this age group,
      including issues of parental involvement and consent for treatment, developmental
      issues, and patient preferences. Several school-based interventions appear
      promising, and many resources are available to provide education for parents,
      youth, and health care providers.

PMID- 16814700
TI  - Advances in diagnosis of adolescent substance abuse.
AB  - Screening and diagnosis of adolescent substance abuse is a challenging but
      achievable component of primary care practice. Successful integration of these
      procedures into office visits requires an understanding of prevalence, risk
      factors, and strategies for prevention and treatment. The authors provide a
      synopsis of recent advances and important issues in this area and propose a
      stepwise, evidence-based approach to evaluation of substance abuse in
      adolescents.

PMID- 16814701
TI  - Adolescents with co-occurring mental health and substance use disorders in
      primary care.
AB  - Co-occurring mental and substance use disorders (COD) among children and
      adolescents present special challenges for family members and primary care
      clinicians. A broad understanding of prevalence rates, etiology, risk and
      protective factors, and intervention strategies is important in promoting
      evidence-based practices. The authors present a synopsis of important issues in
      this area and provide support for integrating behavioral health into primary care
      practice.

PMID- 16814702
TI  - Co-occurring disorders of adolescents in primary care: closing the gaps.
AB  - The increasing prevalence of co-occurring mental health and substance use
      disorders in adolescents is a serious challenge for the primary care system. The
      needs of these youth continue to be underrecognized, poorly diagnosed, and
      inappropriately treated in primary care settings, which are often the first point
      of contact with the health provider system. This article highlights the need for
      changes at the clinical, organizational, and policy levels to create a system of
      care that can effectively identify, refer, treat, and coordinate the care for
      these adolescents and their families.

PMID- 16814703
TI  - Cultural differences in adolescent drug abuse.
AB  - This chapter describes the epidemiology of drug use among adolescents from
      different racial and ethnic groups. Second, it addresses the cultural variables
      prevalent in each of these groups and their relevance in the delivery of clinical
      care. Third, it describes the risks and protective factors for adolescent drug
      use and their interface with culture and the screening tools available for the
      pediatrician. Finally, we present the treatment and model programs of prevention
      that were tested specifically with ethnic groups ranked by the National Registry
      of Evidence-Based Programs.

PMID- 16814704
TI  - TUF love for "junk" DNA.
AB  - The widespread occurrence of noncoding (nc) RNAs--unannotated eukaryotic
      transcripts with reduced protein coding potential--suggests that they are
      functionally important. Study of ncRNAs is increasing our understanding of the
      organization and regulation of genomes.

PMID- 16814705
TI  - Calcium signaling networks channel plant K+ uptake.
AB  - Potassium channel function is fundamental to many physiological processes in
      plants. In this issue of Cell, identify a protein complex in Arabidopsis
      consisting of a potassium channel, a protein kinase, and a calcium sensor. This
      study reveals that plants cope with limited soil potassium by coupling potassium
      channel activation to a cellular calcium signaling network.

PMID- 16814706
TI  - Integrating adhesion, protrusion, and contraction during cell migration.
AB  - Cell migration is fastest when the strength of the adhesion between the cell and
      the substrate is neither too strong nor too weak. In this issue of Cell, reveal
      how adhesion and cytoskeletal dynamics are integrated to optimize migration
      speed.

PMID- 16814707
TI  - Promoter cleavage: a topoIIbeta and PARP-1 collaboration.
AB  - Hormones trigger dramatic changes in the structure and transcriptional activity
      of specific promoters that lead to exchange of repression complexes for
      activation complexes. now show that estrogen-dependent restructuring and
      transcription of the pS2 promoter require the generation of a DNA double-strand
      break by a novel protein complex containing two enzymes, topoisomerase IIbeta and
      poly(ADP-ribose) polymerase.

PMID- 16814708
TI  - Life without centrioles: cilia in the spotlight.
AB  - Centrioles are critical cellular components that form the architectural core of
      both centrosomes and basal bodies, the nucleating structures of cilia. New work,
      including a study in this issue (), highlights the unexpected finding that lack
      of centrioles does not impede development in the fruit fly. Rather, flies reach
      maturity but then die because their sensory neurons lack cilia.

PMID- 16814709
TI  - Cross-species oncogenomics in cancer gene identification.
AB  - The complexity of genomic aberrations in most human tumors hampers delineation of
      the genes that drive the tumorigenic process. In this issue of Cell, and
      demonstrate that cognate mouse tumor models recapitulate these genetic
      alterations with unexpected fidelity. These results indicate that cross-species
      genomic analysis is a powerful strategy to identify the responsible genes and
      assess their oncogenic capacity in the appropriate genetic context.

PMID- 16814710
TI  - In and out of the replication factory.
AB  - In this issue of Cell, use live-fluorescence microscopy to monitor individual
      genomic loci as they replicate in budding yeast. They confirm that DNA is
      recruited to replication factories and show that sister replication forks
      initiated from the same origin are held together within a single replication
      factory.

PMID- 16814711
TI  - Gene amplification: yeast takes a turn.
AB  - The origins of gene amplifications in mammalian cells have been difficult to
      analyze because of secondary genome rearrangements. Recent studies in budding
      yeast, including in this issue of Cell, have provided new insights into the role
      of palindromic sequences in gene amplification.

PMID- 16814712
TI  - Mitochondria: dynamic organelles in disease, aging, and development.
AB  - Mitochondria are the primary energy-generating system in most eukaryotic cells.
      Additionally, they participate in intermediary metabolism, calcium signaling, and
      apoptosis. Given these well-established functions, it might be expected that
      mitochondrial dysfunction would give rise to a simple and predictable set of
      defects in all tissues. However, mitochondrial dysfunction has pleiotropic
      effects in multicellular organisms. Clearly, much about the basic biology of
      mitochondria remains to be understood. Here we discuss recent work that suggests
      that the dynamics (fusion and fission) of these organelles is important in
      development and disease.

PMID- 16814714
TI  - Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene.
AB  - Genomes of human cancer cells are characterized by numerous chromosomal
      aberrations of uncertain pathogenetic significance. Here, in an inducible mouse
      model of melanoma, we characterized metastatic variants with an acquired focal
      chromosomal amplification that corresponds to a much larger amplification in
      human metastatic melanomas. Further analyses identified Nedd9, an adaptor protein
      related to p130CAS, as the only gene within the minimal common region that
      exhibited amplification-associated overexpression. A series of functional,
      biochemical, and clinical studies established NEDD9 as a bona fide melanoma
      metastasis gene. NEDD9 enhanced invasion in vitro and metastasis in vivo of both
      normal and transformed melanocytes, functionally interacted with focal adhesion
      kinase and modulated focal contact formation, and exhibited frequent robust
      overexpression in human metastatic melanoma relative to primary melanoma. Thus,
      comparative oncogenomics has enabled the identification and facilitated the
      validation of a highly relevant cancer gene governing metastatic potential in
      human melanoma.

PMID- 16814713
TI  - Identification and validation of oncogenes in liver cancer using an integrative
      oncogenomic approach.
AB  - The heterogeneity and instability of human tumors hamper straightforward
      identification of cancer-causing mutations through genomic approaches alone.
      Herein we describe a mouse model of liver cancer initiated from progenitor cells
      harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in
      this mouse model and in human hepatocellular carcinomas revealed a recurrent
      amplification at mouse chromosome 9qA1, the syntenic region of human chromosome
      11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis,
      and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the
      genetic context of their amplification, both cIAP1 and Yap accelerated
      tumorigenesis and were required to sustain rapid growth of amplicon-containing
      tumors. Furthermore, cIAP1 and Yap cooperated to promote tumorigenesis. Our
      results establish a tractable model of liver cancer, identify two oncogenes that
      cooperate by virtue of their coamplification in the same genomic locus, and
      suggest an efficient strategy for the annotation of human cancer genes.

PMID- 16814715
TI  - The pattern of gene amplification is determined by the chromosomal location of
      hairpin-capped breaks.
AB  - DNA palindromes often colocalize in cancer cells with chromosomal regions that
      are predisposed to gene amplification. The molecular mechanisms by which
      palindromes can cause gene amplification are largely unknown. Using yeast as a
      model system, we found that hairpin-capped double-strand breaks (DSBs) occurring
      at the location of human Alu-quasipalindromes lead to the formation of
      intrachromosomal amplicons with large inverted repeats (equivalent to
      homogeneously staining regions in mammalian chromosomes) or extrachromosomal
      palindromic molecules (equivalent to double minutes [DM] in mammalian cells). We
      demonstrate that the specific outcomes of gene amplification depend on the
      applied selection, the nature of the break, and the chromosomal location of the
      amplified gene relative to the site of the hairpin-capped DSB. The rules for the
      palindrome-dependent pathway of gene amplification defined in yeast may operate
      during the formation of amplicons in human tumors.

PMID- 16814716
TI  - Live-cell imaging reveals replication of individual replicons in eukaryotic
      replication factories.
AB  - Faithful DNA replication ensures genetic integrity in eukaryotic cells, but it is
      still obscure how replication is organized in space and time within the nucleus.
      Using timelapse microscopy, we have developed a new assay to analyze the dynamics
      of DNA replication both spatially and temporally in individual Saccharomyces
      cerevisiae cells. This allowed us to visualize replication factories, nuclear
      foci consisting of replication proteins where the bulk of DNA synthesis occurs.
      We show that the formation of replication factories is a consequence of DNA
      replication itself. Our analyses of replication at specific DNA sequences support
      a long-standing hypothesis that sister replication forks generated from the same
      origin stay associated with each other within a replication factory while the
      entire replicon is replicated. This assay system allows replication to be studied
      at extremely high temporal resolution in individual cells, thereby opening a
      window into how replication dynamics vary from cell to cell.

PMID- 16814717
TI  - A molecular mousetrap determines polarity of termination of DNA replication in E.
      coli.
AB  - During chromosome synthesis in Escherichia coli, replication forks are blocked by
      Tus bound Ter sites on approach from one direction but not the other. To study
      the basis of this polarity, we measured the rates of dissociation of Tus from
      forked TerB oligonucleotides, such as would be produced by the replicative DnaB
      helicase at both the fork-blocking (nonpermissive) and permissive ends of the Ter
      site. Strand separation of a few nucleotides at the permissive end was sufficient
      to force rapid dissociation of Tus to allow fork progression. In contrast, strand
      separation extending to and including the strictly conserved G-C(6) base pair at
      the nonpermissive end led to formation of a stable locked complex. Lock formation
      specifically requires the cytosine residue, C(6). The crystal structure of the
      locked complex showed that C(6) moves 14 A from its normal position to bind in a
      cytosine-specific pocket on the surface of Tus.

PMID- 16814718
TI  - Cyclin-dependent kinase directly regulates initiation of meiotic recombination.
AB  - Meiosis is a specialized cell division that halves the genome complement,
      producing haploid gametes/spores from diploid cells. Proper separation of
      homologous chromosomes at the first meiotic division requires the production of
      physical connections (chiasmata) between homologs through recombinational
      exchange of chromosome arms after sister-chromatid cohesion is established but
      before chromosome segregation takes place. The events of meiotic prophase must
      thus occur in a strictly temporal order, but the molecular controls coordinating
      these events have not been well elucidated. Here, we demonstrate that the budding
      yeast cyclin-dependent kinase Cdc28 directly regulates the formation of the DNA
      double-strand breaks that initiate recombination by phosphorylating the
      Mer2/Rec107 protein and thereby modulating interactions of Mer2 with other
      proteins required for break formation. We propose that this function of Cdc28
      helps to coordinate the events of meiotic prophase with each other and with
      progression through prophase.

PMID- 16814719
TI  - Intracellular nucleotides act as critical prosurvival factors by binding to
      cytochrome C and inhibiting apoptosome.
AB  - Cytochrome c (CC)-initiated Apaf-1 apoptosome formation represents a key
      initiating event in apoptosis. This process can be reconstituted in vitro with
      the addition of CC and ATP or dATP to cell lysates. How physiological levels of
      nucleotides, normally at high mM concentrations, affect apoptosome activation
      remains unclear. Here we show that physiological levels of nucleotides inhibit
      the CC-initiated apoptosome formation and caspase-9 activation by directly
      binding to CC on several key lysine residues and thus preventing CC interaction
      with Apaf-1. We show that in various apoptotic systems caspase activation is
      preceded or accompanied by decreases in overall intracellular NTP pools.
      Microinjection of nucleotides inhibits whereas experimentally reducing NTP pools
      enhances both CC and apoptotic stimuli-induced cell death. Our results thus
      suggest that the intracellular nucleotides represent critical prosurvival factors
      by functioning as natural inhibitors of apoptosome formation and a barrier that
      cells must overcome the nucleotide barrier to undergo apoptosis cell death.

PMID- 16814720
TI  - A protein kinase, interacting with two calcineurin B-like proteins, regulates K+
      transporter AKT1 in Arabidopsis.
AB  - Potassium is an essential mineral element for plant growth and development.
      Although it is known that plants absorb and transport K+ through membrane
      transporters, it remains unclear how these transporters are regulated. Here we
      show that the protein kinase CIPK23, encoded by the LKS1 gene, regulates K+
      uptake under low-K+ conditions. Lesion of LKS1 significantly reduced K+ uptake
      and caused leaf chlorosis and growth inhibition, whereas overexpression of LKS1
      significantly enhanced K+ uptake and tolerance to low K+. We demonstrate that
      CIPK23 directly phosphorylates the K+ transporter AKT1 and further find that
      CIPK23 is activated by the binding of two calcineurin B-like proteins, CBL1 and
      CBL9. We propose a model in which the CBL1/9-CIPK23 pathway ensures activation of
      AKT1 and enhanced K+ uptake under low-K+ conditions.

PMID- 16814721
TI  - Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes
      rapid cell migration.
AB  - Cells exhibit a biphasic migration-velocity response to increasing adhesion
      strength, with fast migration occurring at intermediate extracellular matrix
      (ECM) concentration and slow migration occurring at low and high ECM
      concentration. A simple mechanical model has been proposed to explain this
      observation, in which too little adhesion does not provide sufficient traction
      whereas too much adhesion renders cells immobile. Here we characterize a
      phenotype for rapid cell migration, which in contrast to the previous model
      reveals a complex interdependence of subcellular systems that mediates optimal
      cell migration in response to increasing adhesion strength. The organization and
      activity of actin, myosin II, and focal adhesions (FAs) are spatially and
      temporally highly variable and do not exhibit a simple correlation with optimal
      motility rates. Furthermore, we can recapitulate rapid migration at a nonoptimal
      ECM concentration by manipulating myosin II activity. Thus, the interplay between
      actomyosin and FA dynamics results in a specific balance between adhesion and
      contraction, which induces maximal migration velocity.

PMID- 16814722
TI  - Flies without centrioles.
AB  - Centrioles and centrosomes have an important role in animal cell organization,
      but it is uncertain to what extent they are essential for animal development. The
      Drosophila protein DSas-4 is related to the human microcephaly protein CenpJ and
      the C. elegans centriolar protein Sas-4. We show that DSas-4 is essential for
      centriole replication in flies. DSas-4 mutants start to lose centrioles during
      embryonic development, and, by third-instar larval stages, no centrioles or
      centrosomes are detectable. Mitotic spindle assembly is slow in mutant cells, and
      approximately 30% of the asymmetric divisions of larval neuroblasts are abnormal.
      Nevertheless, mutant flies develop with near normal timing into morphologically
      normal adults. These flies, however, have no cilia or flagella and die shortly
      after birth because their sensory neurons lack cilia. Thus, centrioles are
      essential for the formation of centrosomes, cilia, and flagella, but, remarkably,
      they are not essential for most aspects of Drosophila development.

PMID- 16814723
TI  - Regulation of body pigmentation by the Abdominal-B Hox protein and its gain and
      loss in Drosophila evolution.
AB  - Hox genes have been implicated in the evolution of many animal body patterns, but
      the molecular events underlying trait modification have not been elucidated.
      Pigmentation of the posterior male abdomen is a recently acquired trait in the
      Drosophila melanogaster lineage. Here, we show that the Abdominal-B (ABD-B) Hox
      protein directly activates expression of the yellow pigmentation gene in
      posterior segments. ABD-B regulation of pigmentation evolved through the gain of
      ABD-B binding sites in a specific cis-regulatory element of the yellow gene of a
      common ancestor of sexually dimorphic species. Within the melanogaster species
      group, male-specific pigmentation has subsequently been lost by at least three
      different mechanisms, including the mutational inactivation of a key ABD-B
      binding site in one lineage. These results demonstrate how Hox regulation of
      traits and target genes is gained and lost at the species level and have general
      implications for the evolution of body form at higher taxonomic levels.

PMID- 16814724
TI  - p53 aerobics: the major tumor suppressor fuels your workout.
AB  - In addition to its role as the central regulator of the cellular stress response,
      p53 can regulate aerobic respiration via the novel transcriptional target SCO2, a
      critical regulator of the cytochrome c oxidase complex (Matoba et al., 2006).
      Loss of p53 results in decreased oxygen consumption and aerobic respiration and
      promotes a switch to glycolysis, thereby reducing endurance during physical
      exercise.

PMID- 16814725
TI  - Xenobiotic metabolism in the fourth dimension: PARtners in time.
AB  - A significant portion of the transcriptome in mammals, including the PAR bZIP
      transcription factors DBP, HLF, and TEF, is under circadian clock control. In
      this issue of Cell Metabolism, Gachon and colleagues (Gachon et al., 2006) show
      that disruption of these three genes in mice alters gene expression patterns of
      many proteins involved in drug metabolism and in liver and kidney responses to
      xenobiotic agents. Triple mutant mice have severe physiological deficits,
      including increased hypersensitivity to xenobiotic agents and premature aging,
      highlighting the profound effect the circadian clock has on this important
      response system.

PMID- 16814726
TI  - APPLied mechanics: uncovering how adiponectin modulates insulin action.
AB  - Adiponectin, an adipocyte secretory hormone, has been causally linked to insulin
      resistance in the metabolic syndrome and diabetes. A recent paper (Mao et al.,
      2006) shows that the APPL1 adaptor protein binds to the intracellular domain of
      adiponectin receptors and mediates some of adiponectin's actions, identifying a
      novel mechanism linking adiponectin to insulin sensitization.

PMID- 16814727
TI  - Designer macrophages: oxidative metabolism fuels inflammation repair.
AB  - Macrophages play a central role in immunity, contributing to both the initiation
      and resolution of inflammation. In this issue of Cell Metabolism, Vats et al.
      provide insight into the mechanisms by which reparative macrophages are generated
      and reveal a previously unappreciated link between this anti-inflammatory axis
      and mitochondrial oxidative metabolism (Vats el al., 2006).

PMID- 16814728
TI  - MicroRNAs: a new class of regulatory genes affecting metabolism.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression by
      binding to target mRNAs, which leads to reduced protein synthesis and sometimes
      decreased steady-state mRNA levels. Although hundreds of miRNAs have been
      identified, much less is known about their biological function. Several studies
      have provided evidence that miRNAs affect pathways that are fundamental for
      metabolic control in higher organisms such as adipocyte and skeletal muscle
      differentiation. Furthermore, some miRNAs have been implicated in lipid, amino
      acid, and glucose homeostasis. These studies open the possibility that miRNAs may
      contribute to common metabolic diseases and point to novel therapeutic
      opportunities based on targeting of miRNAs.

PMID- 16814729
TI  - Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation.
AB  - Complex interplay between T helper (Th) cells and macrophages contributes to the
      formation and progression of atherosclerotic plaques. While Th1 cytokines promote
      inflammatory activation of lesion macrophages, Th2 cytokines attenuate macrophage
      mediated inflammation and enhance their repair functions. In spite of its
      biologic importance, the biochemical and molecular basis of how Th2 cytokines
      promote maturation of anti-inflammatory macrophages is not understood. We show
      here that in response to interleukin-4 (IL-4), signal transducer and activator of
      transcription 6 (STAT6) and PPARgamma-coactivator-1beta (PGC-1beta) induce
      macrophage programs for fatty acid oxidation and mitochondrial biogenesis.
      Transgenic expression of PGC-1beta primes macrophages for alternative activation
      and strongly inhibits proinflammatory cytokine production, whereas inhibition of
      oxidative metabolism or RNAi-mediated knockdown of PGC-1beta attenuates this
      immune response. These data elucidate a molecular pathway that directly links
      mitochondrial oxidative metabolism to the anti-inflammatory program of macrophage
      activation, suggesting a potential role for metabolic therapies in treating
      atherogenic inflammation.

PMID- 16814730
TI  - The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and
      HLF modulate basal and inducible xenobiotic detoxification.
AB  - The PAR-domain basic leucine zipper (PAR bZip) transcription factors DBP, TEF,
      and HLF accumulate in a highly circadian manner in several peripheral tissues,
      including liver and kidney. Mice devoid of all three of these proteins are born
      at expected Mendelian ratios, but are epilepsy prone, age at an accelerated rate,
      and die prematurely. In the hope of identifying PAR bZip target genes whose
      altered expression might contribute to the high morbidity and mortality of PAR
      bZip triple knockout mice, we compared the liver and kidney transcriptomes of
      these animals to those of wild-type or heterozygous mutant mice. These
      experiments revealed that PAR bZip proteins control the expression of many
      enzymes and regulators involved in detoxification and drug metabolism, such as
      cytochrome P450 enzymes, carboxylesterases, and constitutive androstane receptor
      (CAR). Indeed, PAR bZip triple knockout mice are hypersensitive to xenobiotic
      compounds, and the deficiency in detoxification may contribute to their early
      aging.

PMID- 16814731
TI  - The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila.
AB  - Exposure to xenobiotics such as plant toxins, pollutants, or prescription drugs
      triggers a defense response, inducing genes that encode key detoxification
      enzymes. Although xenobiotic responses have been studied in vertebrates, little
      effort has been made to exploit a simple genetic system for characterizing the
      molecular basis of this coordinated transcriptional response. We show here that
      approximately 1000 transcripts are significantly affected by phenobarbital
      treatment in Drosophila. We also demonstrate that the Drosophila ortholog of the
      human SXR and CAR xenobiotic receptors, DHR96, plays a role in this response. A
      DHR96 null mutant displays increased sensitivity to the sedative effects of
      phenobarbital and the pesticide DDT as well as defects in the expression of many
      phenobarbital-regulated genes. Metabolic and stress-response genes are also
      controlled by DHR96, implicating its role in coordinating multiple response
      pathways. This work establishes a new model system for defining the genetic
      control of xenobiotic stress responses.

PMID- 16814732
TI  - Critical role of STAT3 in leptin's metabolic actions.
AB  - Leptin has pleiotropic effects on glucose homeostasis and feeding behavior. Here,
      we validate the use of a cell-permeable phosphopeptide that blocks STAT3
      activation in vivo. The combination of this biochemical approach with stereotaxic
      surgical techniques allowed us to pinpoint the contribution of hypothalamic STAT3
      to the acute effects of leptin on food intake and glucose homeostasis. Leptin's
      ability to acutely reduce food intake critically depends on intact STAT3
      signaling. Likewise, hypothalamic signaling of leptin through STAT3 is required
      for the acute effects of leptin on liver glucose fluxes. Lifelong obliteration of
      STAT3 signaling via the leptin receptor in mice (s/s mice) results in severe
      hepatic insulin resistance that is comparable to that observed in db/db mice,
      devoid of leptin receptor signaling. Our results demonstrate that the activation
      of the hypothalamic STAT3 pathway is an absolute requirement for the effects of
      leptin on food intake and hepatic glucose metabolism.

PMID- 16814733
TI  - Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and
      resistance to diet-induced obesity.
AB  - The mitogen-activated protein kinases (MAPK) play critical roles in the
      pathogenesis of diabetes and obesity. The MAPKs are inactivated by MAPK
      phosphatases (MKPs) either in the cytosol or nucleus. Here we show that mice
      lacking the nuclear-localized MKP, MKP-1 (mkp-1(-/-)), have enhanced Erk, p38
      MAPK and c-Jun NH(2)-terminal kinase (JNK) activities in insulin-responsive
      tissues as compared with wild-type mice. Although JNK promotes insulin
      resistance, mkp-1(-/-) mice exhibited unimpaired insulin-mediated signaling and
      glucose homeostasis. We reconciled these results by demonstrating that in mkp-1(
      /-) mice, JNK activity was increased in the nucleus, but not the cytosol.
      Significantly, mkp-1(-/-) mice are resistant to diet-induced obesity due to
      enhanced energy expenditure, but succumb to glucose intolerance on a high fat
      diet. These results suggest that nuclear regulation of the MAPKs by MKP-1 is
      essential for the management of metabolic homeostasis in a manner that is
      spatially uncoupled from the cytosolic actions of the MAPKs.

PMID- 16814735
TI  - siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1
      in glucose and lipid metabolism in human skeletal muscle.
AB  - Type 2 diabetes is associated with defects in insulin signaling and the resulting
      abnormal glucose and lipid metabolism. The complexity of insulin signaling
      cascades is highlighted by the existence of multiple isoforms of target proteins
      implicated in metabolic and gene-regulatory events. We utilized siRNA to decipher
      the specific role of predominant insulin receptor substrates and Akt isoforms
      expressed in human skeletal muscle. Gene silencing revealed specialized roles of
      insulin signaling cascades to metabolic endpoints. IRS-1 and Akt2 were required
      for myoblast differentiation and glucose metabolism, whereas IRS-2 and Akt1 were
      dispensable. A key role of IRS-2 and Akt1 in lipid metabolism was revealed,
      highlighting reciprocal relationships between metabolic pathways. Unraveling the
      isoform-specific regulation of glucose and lipid metabolism by key elements along
      insulin signaling cascades through siRNA-mediated gene silencing in human tissues
      will facilitate the discovery of novel targets for the treatment of diabetes and
      related metabolic disorders.

PMID- 16814736
TI  - Effect of salts and organic additives on the solubility of proteins in aqueous
      solutions.
AB  - The goal of this review is to examine the effect of salts and organic additives
      on the solubility of proteins in aqueous mixed solvents. The focus is on the
      correlation between the aqueous protein solubility and the osmotic second virial
      coefficient or the preferential binding parameter. First, several approaches
      which connect the solubility and the osmotic second virial coefficient are
      presented. Most of the experimental and theoretical results correlate the
      solubility and the osmotic second virial coefficient in the presence of salts.
      The correlation of the aqueous protein solubility with the osmotic second virial
      coefficient when the cosolvent is an organic component requires additional
      research. Second, the aqueous protein solubility is correlated with the
      preferential binding parameter on the basis of a theory developed by the authors
      of the present review. This theory can predict (i) the salting-in or -out effect
      of a cosolvent and (ii) the initial slope of the solubility curve. Good agreement
      was obtained between theoretical predictions and experimental results.

PMID- 16814737
TI  - Homogeneous time-resolved fluorescence and its applications for kinase assays in
      drug discovery.
AB  - The rapidly growing interest in kinases as potential targets for therapeutic
      intervention has prompted the development of many kinase assay technologies. One
      exciting example is homogeneous time-resolved fluorescence (HTRF). An HTRF assay
      utilizes the signal generated by the fluorescence resonance energy transfer
      between donor and acceptor molecules in close proximity. Dual-wavelength
      detection helps to eliminate media interference, and the final signal is
      proportional to the extent of product formation. Thus far, the reported
      applications of this technology for in vitro kinase assays have mainly focused on
      high-throughput screening. In this report, we extend the applications of HTRF
      technology to the areas of enzyme and inhibitor characterization, some aspects of
      which were previously believed impossible. We describe the methods developed for
      determining the kinetic parameters of an enzyme, such as K(m) and k(cat), and the
      procedures for inhibitor mechanistic studies including ATP competitiveness and
      slow-binding and dissociation kinetics. These assays can be readily applied to
      any kinase and are valuable in advancing a program through the early stages of
      drug discovery.

PMID- 16814734
TI  - Role of adiponectin in human skeletal muscle bioenergetics.
AB  - Insulin resistance is associated with impaired skeletal muscle oxidation capacity
      and reduced mitochondrial number and function. Here, we report that adiponectin
      signaling regulates mitochondrial bioenergetics in skeletal muscle. Individuals
      with a family history of type 2 diabetes display skeletal muscle insulin
      resistance and mitochondrial dysfunction; adiponectin levels strongly correlate
      with mtDNA content. Knockout of the adiponectin gene in mice is associated with
      insulin resistance and low mitochondrial content and reduced mitochondrial enzyme
      activity in skeletal muscle. Adiponectin treatment of human myotubes in primary
      culture induces mitochondrial biogenesis, palmitate oxidation, and citrate
      synthase activity, and reduces the production of reactive oxygen species. The
      inhibition of adiponectin receptor expression by siRNA, or of AMPK by a
      pharmacological agent, blunts adiponectin induction of mitochondrial function.
      Our findings define a skeletal muscle pathway by which adiponectin increases
      mitochondrial number and function and exerts antidiabetic effects.

PMID- 16814738
TI  - Micro method for determination of nonesterified fatty acid in whole blood
      obtained by fingertip puncture.
AB  - Diagnostic tools for early identification of subjects at high risk for type 2
      diabetes and other obesity-related disorders are important in prevention of these
      diseases. Nonesterified fatty acids (NEFAs) have been suggested to serve as a
      prediagnostic marker of diabetes and obesity-related disorders. In the current
      study, we developed a sensitive and reproducible micro method for quantification
      of NEFA in less than 10 microl whole blood. The method involves only two steps:
      (i) conversion of NEFA to fatty acid acyl-coenzyme A (acyl-CoA) esters using an
      acyl-CoA synthetase and (ii) quantification of the formed acyl-CoA esters with a
      fluorescent biosensor based on bovine acyl-CoA binding protein (ACBP). Lys50 of
      ACBP was mutagenized to a cysteine residue that was covalently modified with 6
      bromoacetyl-2-dimethylaminonaphthalene to make a fluorescent acyl-CoA indicator
      (FACI-50). FACI-50 exhibits high fluorescence emission yield with maximum at 490
      nm in the presence of CoA when excited at 387 nm. The addition of palmitoyl-CoA
      to a CoA-saturated FACI-50 lowered fluorescence emission by eightfold. Ethanol
      extract from 1 microl whole blood was incubated with ATP, CoA, and FACI-50.
      Following background fluorescence reading, NEFAs were converted to acyl-CoA by
      the acyl-CoA synthetase and the NEFA content was calculated from fluorescence
      emission changes using palmitic acid as external standard. The FACI-50 NEFA
      method was compared with two commercially available methods for quantification of
      NEFA.

PMID- 16814739
TI  - Control of laparoscopic instrument motion in an inanimate bench model:
      implications for the training and the evaluation of technical skills.
AB  - Computer-assisted analysis of wrist movement has recently emerged as an objective
      laparoscopic performance evaluation method. The first purpose of this study was
      to assess the differences in motion characteristics between the tip of the
      instrument and the wrist. The second purpose was to describe the control
      strategies used to move laparoscopic instruments. During a bead transfer task,
      motions of a laparoscopic needle driver's tip, heel, and the participants' wrist
      were monitored. Results showed that large amplitude movements were best described
      by movements of the wrist, and small amplitude movements were evidenced by
      motions of the instrument tip. Thus, for describing expertise, and for evaluation
      and feedback, motion of the tip of the laparoscopic instrument should be
      quantified, in addition to motion of the wrist. The motions of the instrument
      were controlled by utilizing the flexibility of the skin of the laparoscopic
      trainer in addition to using the fulcrum, and sliding through the trocar. In
      order to increase fidelity, virtual reality trainers should simulate the
      flexibility of the real structures around the insertion of the instrument.

PMID- 16814740
TI  - Expression and characterization of a functional canine variant of cytochrome b5
      reductase.
AB  - Cytochrome b5 reductase (cb5r), a member of the flavoprotein transhydrogenase
      family of oxidoreductase enzymes, catalyzes the transfer of reducing equivalents
      from the physiological electron donor, NADH, to two molecules of cytochrome b5.
      We have determined the correct nucleotide sequence for the putative full-length,
      membrane-associated enzyme from Canis familiaris, and have generated a
      heterologous expression system for production of a histidine-tagged variant of
      the soluble, catalytic diaphorase domain, comprising residues I33 to F300. Using
      a simple two-step chromatographic procedure, the recombinant diaphorase domain
      has been purified to homogeneity and demonstrated to be a simple flavoprotein
      with a molecular mass of 31,364 (m/z) that retained both NADH:ferricyanide
      reductase and NADH:cytochrome b5 reductase activities. The recombinant protein
      contained a full complement of FAD and exhibited absorption and CD spectra
      comparable to those of a recombinant form of the rat cytochrome b5 reductase
      diaphorase domain generated using an identical expression system, suggesting
      similar protein folding. Oxidation-reduction potentiometric titrations yielded a
      standard midpoint potential (Eo') for the FAD/FADH2 couple of -273+/-5 mV which
      was identical to the value obtained for the corresponding rat domain. Thermal
      denaturation studies revealed that the canine domain exhibited stability
      comparable to that of the rat protein, confirming similar protein conformations.
      Initial-rate kinetic studies revealed the canine diaphorase domain retained a
      marked preference for NADH versus NADPH as reducing substrate and exhibited
      kcat's of 767 and 600 s(-1) for NADH:ferricyanide reductase and NADH:cytochrome
      b5 reductase activities, respectively, with Km's of 7, 8, and 12 microM for NADH,
      K3Fe(CN)6, and cytochrome b5, respectively. Spectral-binding constants (Ks)
      determined for a variety of NAD+ analogs indicated the highest and lowest
      affinities were observed for APAD+ (Ks=71 microM) and PCA+ (Ks=>31 mM),
      respectively, and indicated the binding contributions of the various portions of
      the pyridine nucleotide. These results provide the first correct sequence for the
      full-length, membrane-associated form of C. familiaris cb5r and provide a direct
      comparison of the enzymes from two phylogenetic sources using identical
      expression systems that indicate that both enzymes have comparable spectroscopic,
      kinetic, thermodynamic, and structural properties.

PMID- 16814741
TI  - Histological and histomorphometrical changes in rat alveolar bone following
      antagonistic tooth extraction and/or ovariectomy.
AB  - OBJECTIVE: To examine changes appearing in the alveolar bone following the
      removal of the mechanical stress of occlusal loading, as well as the added
      influence of estrogen deficiency on such changes. DESIGN: The right mandibular
      molars of female rats were extracted. After 8 weeks, 12 animals were
      ovariectomized (OVX), and the other 12 were subjected to sham surgery (sham).
      Four weeks after surgery, all rats were sacrificed. The left-half and right-half
      maxillas of the sham group (the sham-occluded side and the sham-extruded side,
      respectively) and right-half maxilla of OVX group (the OVX-extruded side) were
      examined by histological observation and bone histomorphometry. RESULTS: The
      vertical height of alveolar bone in the sham-extruded and the OVX-extruded sides
      increased as compared with that of the sham-occluded side. In both extruded
      sides, active bone formation occurred on the surface of the alveolar bone facing
      the periodontal ligament, but the bone marrow was expanded and the bone volume
      had decreased in the internal area of the alveolar bone. In the OVX-extruded
      side, the bone marrow expanded more remarkably than that of the sham-extruded
      side, and the highest percentage of osteoclast surface was detected. CONCLUSIONS:
      Around the extruded teeth, there were regional differences in bone dynamics
      between the internal area of the alveolar bone and the bone surface facing the
      periodontal ligament, and estrogen deficiency seems to have caused further loss
      of bone volume in the interior of the alveolar bone supporting the extruded
      tooth.

PMID- 16814742
TI  - Myoglobin with modified tetrapyrrole chromophores: binding specificity and
      photochemistry.
AB  - Complexes were prepared of horse heart myoglobin with derivatives of
      (bacterio)chlorophylls and the linear tetrapyrrole, phycocyanobilin. Structural
      factors important for binding are (i) the presence of a central metal with open
      ligation site, which even induces binding of phycocyanobilin, and (ii) the
      absence of the hydrophobic esterifying alcohol, phytol. Binding is further
      modulated by the stereochemistry at the isocyclic ring. The binding pocket can
      act as a reaction chamber: with enolizable substrates, apo-myoglobin acts as a
      13(2)-epimerase converting, e.g., Zn-pheophorbide a' (13(2)S) to a (13(2)R).
      Light-induced reduction and oxidation of the bound pigments are accelerated as
      compared to solution. Some flexibility of the myoglobin is required for these
      reactions to occur; a nucleophile is required near the chromophores for
      photoreduction (Krasnovskii reaction), and oxygen for photooxidation. Oxidation
      of the bacteriochlorin in the complex and in aqueous solution continues in the
      dark.

PMID- 16814743
TI  - Diagnosing benign and malignant lesions in breast tissue sections by using IR
      microspectroscopy.
AB  - The collection of IR spectra through microscope optics and the visualization of
      the IR data by IR imaging represent a visualization approach, which uses infrared
      spectral features as a native intrinsic contrast mechanism. To illustrate the
      potential of this spectroscopic methodology in breast cancer research, we have
      acquired IR-microspectroscopic data from benign and malignant lesions in breast
      tissue sections by point microscopy with spot sizes of 30-40 microm. Four classes
      of distinct breast tissue spectra were defined and stored in the data base:
      fibroadenoma (a total of 1175 spectra from 14 patients), ductal carcinoma in situ
      (a total of 1349 spectra from 8 patients), connective tissue (a total of 464
      spectra), and adipose tissue (a total of 146 spectra). Artifical neural network
      analysis, a supervised pattern recognition method, was used to develop an
      automated classifier to separate the four classes. After training the artifical
      neural network classifier, infrared spectra of independent external validation
      data sets ("unknown spectra") were analyzed. In this way, all spectra (a total of
      386) taken from micro areas inside the epithelium of fibroadenomas from 4
      patients were correctly classified. Out of the 421 spectra taken from micro areas
      of the in situ component of invasive ductal carcinomas of 3 patients, 93% were
      correctly identified. Based on these results, the potential of the IR
      microspectroscopic approach for diagnosing breast tissue lesions is discussed.

PMID- 16814744
TI  - A randomised placebo-controlled trial of a self-help Internet-based intervention
      for test anxiety.
AB  - Test anxiety is widespread and associated with poor performance in academic
      examinations. The Internet, not well-proven for the treatment of anxiety, should
      be able to deliver highly accessible Cognitive Behavior Therapy (CBT). This study
      sought to test the hypothesis that CBT, available on the Internet, could reduce
      test anxiety. Ninety university students were randomly allocated to CBT or a
      control program, both on the Internet. Before and after treatment, the
      participants completed the Test Anxiety Inventory (TAI), an Anxiety Hierarchy
      Questionnaire (AHQ), the Exam Problem-Solving Inventory (EPSI), the General Self
      Efficacy Scale (GSES) and the Heim reasoning tests (AH) as a measure of test
      performance. Of the CBT and control groups 28% and 35%, respectively, withdrew.
      According to the TAI, 53% of the CBT group showed a reliable and clinically
      significant improvement with treatment but only 29% of the control group
      exhibited such a change. On the AHQ, 67% of the CBT group and 36% of the control
      group showed a clinically significant improvement, more than two standard
      deviations above the mean of the baseline, a change in favour of CBT. Both groups
      improved on the GSES, in state anxiety during exams retrospectively assessed, and
      on the AH tests. The improvement on the AH tests was probably a practice effect
      and not a reflection of a change in capacity for academic testing. This study
      thus supports use of CBT on the Internet for the treatment of test anxiety.

PMID- 16814745
TI  - DIXDC1 isoform, l-DIXDC1, is a novel filamentous actin-binding protein.
AB  - Ccd1, a DIX domain containing Zebrafish protein involved in neural patterning, is
      a positive regulator of the Wnt signaling pathway. DIXDC1, the human homolog of
      Ccd1, has two predominant isoforms. The short form (s-DIXDC1) has a similar amino
      acid sequence compared with Ccd1, while the long form (l-DIXDC1) contains an
      extra N-terminal sequence containing a calponin-homology (CH) domain, suggesting
      additional interaction with actin that we have performed detailed analysis in
      this report. We show that mRNA expression of both DIXDC1 isoforms can be detected
      in various adult tissues by Northern blot analysis and is most abundant in
      cardiac and skeletal muscles. Both endogenous and ectopically expressed l-DIXDC1,
      but not s-DIXDC1, in cultured mammalian cells is localized to actin stress fibers
      at the filament ends in focal adhesion plaques. More importantly, l-DIXDC1 can
      directly bind to filamentous actin both in vitro and in vivo and the binding is
      mediated via a novel actin-binding domain (ABD) from amino acid 127 to 300. Thus,
      our data provide the first evidence that l-DIXDC1 may act as a novel branching
      component in the Wnt signaling pathway targeting both beta-catenin-TCF complex
      for gene expression and cytoskeleton for regulating dynamics of actin filaments.

PMID- 16814746
TI  - Proliferation and differentiation of bone marrow stromal cells under hypoxic
      conditions.
AB  - Low oxygen tension is a potent differentiation inducer of numerous cell types and
      an effective stimulus of many gene expressions. Here, we described that under 8%
      O(2), bone marrow stromal cells (MSCs) exhibited proliferative and morphologic
      changes. The level of differentiated antigen H-2Dd and the number of G(2)/S/M
      phase cells increased evidently under 8% O(2) condition. Also, the proportion of
      wide, flattened, and epithelial-like cells (which were alkaline phosphatase
      staining positive) in MSCs increased significantly. When cultured in adipogenic
      medium, there was a 5- to 6-fold increase in the number of lipid droplets under
      hypoxic conditions compared with that in normoxic culture. We also demonstrated
      the existence of MSC differentiation under hypoxic conditions by electron
      microscopy. Expression of Oct4 was inhibited under 8% O(2) condition, but after
      adipocyte differentiation in normoxic culture and hypoxia-mimicking agents cobalt
      chloride (CoCl(2)) and deferoxamine mesylate (DFX) treatments, Oct4 was still
      expressed in MSCs. These results indicate hypoxia accelerates MSC differentiation
      and hypoxia and hypoxia-mimicking agents exert different effects on MSC
      differentiation.

PMID- 16814747
TI  - Metabolism of the soyabean isoflavone daidzein by CYP1A2 and the extra-hepatic
      CYPs 1A1 and 1B1 affects biological activity.
AB  - Metabolism of the isoflavones daidzein and genistein, which may protect against
      some cancers, was studied using human liver microsomes and recombinant CYP
      isoforms. The detection of three, more polar metabolites of each isoflavone by RP
      HPLC required NADPH, consistent with CYP-mediated metabolism. For different liver
      preparations, metabolite generation from daidzein showed a significant linear
      correlation with metabolite generation from genistein, indicating metabolism by
      the same CYP(s). The lowest rate of metabolism of both isoflavones was by the
      preparation with the lowest CYP1A2 activity. Metabolite peak areas were
      substantially and significantly reduced by the CYP1A2 inhibitor furafylline and
      to a lesser extent by the CYP2E1 inhibitor 4-methylpyrazole. Recombinant CYP1A2,
      but not CYP2E1, generated the metabolites of daidzein and genistein and
      recombinant CYP1A1 and CYP1B1, expressed at sites including the breast and
      prostate, were also active. The effects of two CYP-derived metabolites of
      daidzein, 6,7,4'-trihydroxyisoflavone and 7,3',4'-trihydroxyisoflavone, were
      studied in the MCF-7 human breast cancer cell line at a concentration (50 microM)
      at which daidzein induces an antiproliferative response. 7,3',4'
      Trihydroxyisoflavone reduced total cell numbers to a greater extent than 6,7,4'
      trihydroxyisoflavone or daidzein and increased cell death. Together, these data
      demonstrate proof of principle that CYP-mediated metabolism of daidzein can be an
      activation pathway. We conclude that CYP1A2 makes the major contribution to the
      hepatic metabolism of both daidzein and genistein and along with metabolism at
      sites of hormone-dependent tumours may enhance a cancer-protective effect of
      daidzein if sufficiently high concentrations are reached in target tissues.

PMID- 16814748
TI  - Subchronic phencyclidine treatment decreases the number of dendritic spine
      synapses in the rat prefrontal cortex.
AB  - BACKGROUND: A growing body of evidence suggests the existence of synaptic
      pathology in schizophrenia. Here we used the phencyclidine schizophrenia model to
      directly investigate at the electron microscopic level whether structural
      synaptic alterations are present in these animals. METHODS: Adult male rats were
      treated according to our subchronic phencyclidine paradigm (5 mg/kg twice daily
      for 7 days, intraperitoneally). Following a one-week withdrawal period, the
      number of prefrontal cortical spine synapses was calculated using an unbiased
      electron microscopic stereological approach. The number of astroglia cells and
      the density of their processes was also analyzed following glial-fibrillary
      acidic protein immunohistochemistry. RESULTS: Subchronic phencyclidine treatment
      resulted in a 41.2% decrease in the number of prefrontal spine synapses when
      compared to controls. This was accompanied by a 58.8% increase in astroglia
      process density, without significant change in the number of astroglia cells.
      CONCLUSIONS: Our results demonstrate a severe reduction in the number of
      prefrontal spine synapses in an animal model of schizophrenia. This phenomenon
      may contribute to phencyclidine-induced cognitive dysfunction and decreased
      prefrontal cellular activity observed in this model.

PMID- 16814749
TI  - Apoptosis induced by prolonged exposure to odorants in cultured cells from rat
      olfactory epithelium.
AB  - Multicellular organisms undergo programmed cell death (PCD) as a mechanism for
      tissue remodeling during development and tissue renewal throughout adult life.
      Overdose of some neuronal receptor agonists like glutamate can trigger a PCD
      process termed excitotoxicity in neurons of the central nervous system. Calcium
      has an important role in PCD processes, especially in excitotoxicity. Since the
      normal turnover of olfactory receptor neurons (ORNs) relies, at least in part, on
      an apoptotic mechanism and odor transduction in ORNs involves an increase in
      intracellular Ca2+ concentration ([Ca2+]i), we investigated the possibility that
      long-term exposures to odorants could trigger an excitotoxic process in olfactory
      epithelial cells (EC). We used single-cell [Ca2+]i determinations and
      fluorescence microscopy techniques to study the effects of sustained odorant
      exposures in olfactory EC in primary culture. Induction of PCD was evaluated
      successively by three independent criteria: (1) measurements of DNA
      fragmentation, (2) translocation of phosphatidylserine to the external leaflet of
      the plasma membrane, and (3) caspase-3 activation. Our results support the notion
      of an odorant-induced PCD in olfactory EC. This odorant-induced PCD was prevented
      by LY83583, an odorant response inhibitor, suggesting that ORNs are the main
      epithelial cell population undergoing odorant-induced PCD.

PMID- 16814750
TI  - Fibronectin and neuroprotective effect of granulocyte colony-stimulating factor
      in focal cerebral ischemia.
AB  - Stroke is one of the leading causes of unnatural death and disability. No
      effective therapy is available. Recombinant human granulocyte colony-stimulating
      factor (rhG-CSF), as a mobilizing agent for bone marrow stem cells, can promote
      stem cell mobilization, homing to brain after cerebral ischemia. In the present
      study, the administration of G-CSF significantly increased number of CD34(+)
      cells in the marginal zone of the infarction. Rats receiving G-CSF had higher
      survival rate and lower infarction volume. Neurological behavior was improved,
      and the expression of fibronectin in the ischemic brain was increased, as
      compared to rats treated with vehicle. To mimic the ischemia-reperfusion injury
      in experimental animals, we employed hippocampal slice cultures that were first
      treated with oxygen and glucose deprivation (OGD) and then with oxygen-glucose
      resupply, finding that fibronectin significantly increased the neurite outgrowth
      of OGD hippocampal slices, upregulated the expression of Bcl-2 protein, and
      ameliorated the ultrastructure damage of OGD hippocampal slices.

PMID- 16814751
TI  - The influence of sex and social isolation housing on pre- and postsynaptic 5-HT1A
      receptors.
AB  - Serotonergic (5-HT) receptors are crucial for different brain functions and play
      an important role in several pathological conditions. We analysed [3H]8-OH-DPAT
      specific binding to 5-HT1A receptors in male and female mice after group or
      isolation housing by in vitro autoradiography (n = 6 per group). Females
      displayed higher postsynaptic 5-HT1A receptor binding compared to males,
      especially in the cortex. In contrast, lower [3H]8-OH-DPAT-specific binding was
      found in the female hippocampus. No sex difference was seen for the
      somatodendritic 5-HT1A autoreceptor. Sex differences in postsynaptic 5-HT1A
      receptor binding should be relevant to behavioural sex differences, especially in
      locomotor activity and hippocampus-dependent behaviours. Six weeks isolation
      housing caused an increase in 5-HT1A receptor binding in most of the brain
      regions analysed and was more pronounced in males. In isolated males, the
      increases were detected in the CA1 field of the hippocampus (+16.8%), in the
      septum (+76.8%), in the cortical amygdala (+24.6%), in the periaqueductal gray
      (+67.2%) and in the different cortical regions analysed (+61.8-81.4%). [3H]8-OH
      DPAT-specific binding increased significantly in the dentate gyrus (+47.1%), the
      supramammillary nucleus (+31.2%) and in the ventromedial hypothalamus (+34.4%) of
      isolated females. Sex-dependent isolation-induced alterations in [3H]8-OH-DPAT
      specific binding were also found in the raphe nuclei. Isolation-induced increases
      in 5-HT1A receptor binding could be relevant to the behavioural disinhibition
      with heightened arousal, impulsivity and activity often observed in isolates. The
      male-specific alterations in the corticolimbic system as well as in the midbrain
      could be crucial for isolation-induced aggression.

PMID- 16814752
TI  - Role of Clast1 in development of cerebellar granule cells.
AB  - We have identified the murine Clast1/LR8 gene by subtraction of cDNA derived from
      CD40 ligand-activated and naive B cells. The Clast1 gene is ubiquitously
      expressed in various organs of adult mice. However, its physiological function
      was largely unknown. To study a role of Clast1, we established Clast1-deficient
      (Clast1-KO) mice. Here, we reveal that approximately 65% of Clast1-KO mice showed
      severe ataxia. The Clast1-KO cerebellum with ataxia is small in size and revealed
      a severely aberrant lobulation, loss of the internal granule cell layer, and the
      disorganized Purkinje cells. Clast1 mRNA is expressed in the cerebellar granule
      cells of normal adult mice. Developmentally, Clast1 mRNA is also detected in the
      external germinal layer of the embryonic cerebellum, indicating its expression in
      granule cell precursors. Histopathological analysis of the developing Clast1-KO
      cerebellum demonstrated the reduced number of cells in the external germinal
      layer. Thus, Clast1 is required for development of cerebellar granule cells.

PMID- 16814753
TI  - Transient ischemia-induced changes of interleukin-2 and its receptor beta
      immunoreactivity and levels in the gerbil hippocampal CA1 region.
AB  - Interlukin-2 (IL-2) is an important cytokine in the brain: IL-2 and its receptors
      are involved with inflammatory processes. Chronological changes in IL-2 level in
      serum, and IL-2 and its receptor (IL-2 receptor beta, IL-2Rbeta)
      immunoreactivities and levels were examined in the hippocampal CA1 region after
      transient forebrain ischemia in gerbils. IL-2 level in serum significantly
      decreased 12 h after ischemia/reperfusion. IL-2 immunoreactivity was detected in
      the somata of pyramidal cells in sham-operated group. At 15 min after ischemia,
      IL-2 immunoreactivity was shown in non-pyramidal cells as well as pyramidal
      cells. One day after ischemia, IL-2 immunoreactivity was lowest, and IL-2
      immunoreactivity is shown in non-pyramidal cells from 2 days after ischemia. Four
      days after ischemia, IL-2 immunoreactivity was shown in dying pyramidal cells. IL
      2Rbeta immunoreactivity in the sham-operated and 15 min-3 min post-ischemic
      groups is detected in the cell membrane of pyramidal cells. From 3 h after
      ischemia, IL-2Rbeta immunoreactivity is found in cytoplasm and nuclei, but not in
      cell membrane. IL-2Rbeta immunoreactivity decreases from 6 h after ischemia and
      is shown mainly in non-pyramidal cells from 3 days after ischemia. The data of
      Western blot analyses for IL-2 and IL-2Rbeta was similar to the
      immunohistochemical data. IL-2 infusion into cerebrospinal fluid did not protect
      hippocampal neurons from ischemic damage. These results suggest that IL-2 and IL
      2Rbeta show malfunction from 3 h after ischemia, and exogenous IL-2 does not
      protect ischemic neuronal damage.

PMID- 16814754
TI  - Blocker-resistant presynaptic voltage-dependent Ca2+ channels underlying
      glutamate release in mice nucleus tractus solitarii.
AB  - The visceral sensory information from the internal organs is conveyed via the
      vagus and glossopharyngeal primary afferent fibers and transmitted to the second
      order neurons in the nucleus of the solitary tract (NTS). The glutamate release
      from the solitary tract (TS) axons to the second-order NTS neurons remains even
      in the presence of toxins that block N- and P/Q-type voltage-dependent Ca(2+)
      channels (VDCCs). The presynaptic VDCC playing the major role at this synapse
      remains unidentified. To address this issue, we examined two hypotheses in this
      study. First, we examined whether the remaining large component occurs through
      activation of a omega-conotoxin GVIA (omega-CgTX)-insensitive variant of N-type
      VDCC by using the mice genetically lacking its pore-forming subunit alpha(1B).
      Second, we examined whether R-type VDCCs are involved in transmitter release at
      the TS-NTS synapse. The EPSCs evoked by stimulation of the TS were recorded in
      medullary slices from young mice. omega-Agatoxin IVA (omega-AgaIVA; 200 nM) did
      not significantly affect the EPSC amplitude in the mice genetically lacking N
      type VDCC. SNX-482 (500 nM) and Ni(2+) (100 microM) did not significantly reduce
      EPSC amplitude in ICR mice. These results indicate that, unlike in most of the
      brain synapses identified to date, the largest part of the glutamate release at
      the TS-NTS synapse in mice occurs through activation of non-L, non-P/Q, non-R,
      non-T and non-N (including its posttranslational variants) VDCCs at least
      according to their pharmacological properties identified to date.

PMID- 16814755
TI  - Cholesterol-enriched diet affects spatial learning and synaptic function in
      hippocampal synapses.
AB  - The aim of the present study was to determine the effect of a cholesterol-rich
      diet on learning performance and monitor possible related changes in synaptic
      function. To this purpose, we compared controls with rats fed with a cholesterol
      enriched diet (CD). By using a Morris water-maze paradigm, we found that CD rats
      learned a water-maze task more quickly than rats fed with a regular diet (RD). A
      longer period of this diet tended to alter the retention of memory without
      affecting the improvement in the acquisition of the task. Because of the
      importance of the hippocampus in spatial learning, we hypothesized that these
      behavioral effects of cholesterol would involve synaptic changes at the
      hippocampal level. We used whole-cell patch-clamp recording in the CA1 area of a
      hippocampal rat slice preparation to test the influence of the CD on pre- and
      postsynaptic function. CD rats displayed an increase in paired-pulse ratio in
      both glutamatergic synapses (+48 +/- 9%) and GABAergic synapses (+41 +/- 8%),
      suggesting that the CD induces long-lasting changes in presynaptic function.
      Furthermore, by recording NMDA-receptor-mediated currents (I(NMDA)) and AMPA
      receptor-mediated currents (I(AMPA)) in the same set of cells we found that CD
      rats display a lower I(NMDA)/I(AMPA) ratio (I(NMDA)/I(AMPA) = 0.75 +/- 0.32 in RD
      versus 0.10 +/- 0.03 in CD), demonstrating that cholesterol regulates also
      postsynaptic function. We conclude that a cholesterol-rich diet affects learning
      speed and performance, and that these behavioral changes occur together with
      robust, long-lasting, synaptic changes at both the pre- and postsynaptic level.

PMID- 16814756
TI  - Participation of the hippocampal theta rhythm in memory formation for an eight
      arm radial maze task in rats.
AB  - Participation of the hippocampal theta rhythm in memory formation was studied
      using an eight-arm radial maze task in rats. The numbers of reference memory and
      working memory errors were decreased gradually by daily training from session 10
      and 6, respectively. On the other hand, the decrease in running time per choice
      was recognized from session 3. Theta power in the hippocampal CA1 area was
      gradually decreased from session 9, and there is a close relationship between the
      changes in theta power in the hippocampus and the number of reference memory
      errors. Based on those observations, it can be concluded that the hippocampal
      theta wave is intimately associated with the reference memory of the eight-arm
      radial maze in rats.

PMID- 16814757
TI  - Biology of atherosclerotic plaques: what we are learning from proteomic analysis.
AB  - Atherosclerotic plaque rupture triggers the onset of cardiovascular complications
      such as myocardial infarction and stroke, which represent the main cause of death
      in western countries. Atherogenesis is a complex process characterized by lipid
      retention, proteolytic injury and a chronic inflammatory response. The resulting
      pathological vascular remodeling involves inflammatory cell recruitment,
      fibrosis, smooth muscle cell proliferation, neovascularization and intraplaque
      hemorrhage. However, the cellular and molecular mechanisms underlying
      cardiovascular dysfunction remain widely unknown. The development of differential
      proteomics allows the identification of novel proteins whose association with the
      genesis of atherosclerotic plaques is at present unforeseen in the light of
      available data. Moreover, different strategies have been used to discover new
      potential biomarkers which could be related to cardiovascular risk. The multi
      factorial nature of cardiovascular diseases necessitates the use of biomarkers
      for early detection, for monitoring the response to therapy and to predict
      clinical outcome. In this review, we summarize the different proteomic approaches
      and recent findings that will help us to understand the mechanisms implicated in
      the pathogenesis of atherothrombosis.

PMID- 16814758
TI  - The calcium channel blocker amlodipine promotes the unclamping of eNOS from
      caveolin in endothelial cells.
AB  - OBJECTIVES: Amlodipine is a calcium channel blocker (CCB) known to stimulate
      nitric oxide production from endothelial cells. Whether this ancillary property
      can be related to the capacity of amlodipine to concentrate and alter the
      structure of cholesterol-containing membrane bilayers is a matter of
      investigation. Here, we reasoned that since the endothelial nitric oxide synthase
      is, in part, expressed in cholesterol-rich plasmalemmal microdomains (e.g.,
      caveolae and rafts), amlodipine could interfere with this specific locale of the
      enzyme and thereby modulate NO production in endothelial cells. METHODS AND
      RESULTS: Using a method combining lubrol-based extraction and subcellular
      fractionation on sucrose gradient, we found that amlodipine, but not verapamil or
      nifedipine, induced the segregation of endothelial NO synthase (eNOS) from
      caveolin-enriched low-density membranes (8+/-2% vs. 42+/-3% in untreated
      condition; P<0.01). We then performed co-immunoprecipitation experiments and
      found that amlodipine dose-dependently disrupted the caveolin/eNOS interaction
      contrary to other calcium channel blockers, and potentiated the stimulation of NO
      production by agonists such as bradykinin and vascular endothelial growth factor
      (VEGF) (+138+/-28% and +183+/-27% over values obtained with the agonist alone,
      respectively; P<0.01). Interestingly, we also documented that the dissociation of
      the caveolin/eNOS heterocomplex induced by amlodipine was not mediated by the
      traditional calcium-dependent calmodulin binding to eNOS and that recombinant
      caveolin expression could compete with the stimulatory effects of amlodipine on
      eNOS activity. Finally, we showed that the amlodipine-triggered, caveolin
      dependent mechanism of eNOS activation was independent of other pleiotropic
      effects of the CCB such as superoxide anion scavenging and angiotensin-converting
      enzyme (ACE) inhibition. CONCLUSIONS: This study unravels the modulatory effects
      of amlodipine on caveolar integrity and the capacity of caveolin to maintain eNOS
      in its vicinity in the absence of any detectable changes in intracellular calcium
      levels. The resulting increase in caveolin-free eNOS potentiates the NO
      production in response to agonists including VEGF and bradykinin. More generally,
      this work opens new avenues of treatment for drugs able to structurally alter
      signaling pathways concentrated in caveolae.

PMID- 16814759
TI  - Mitochondrial function and toxicity: role of B vitamins on the one-carbon
      transfer pathways.
AB  - The B vitamins are water-soluble vitamins that are required as coenzymes for
      reactions essential for cellular function. This review focuses on the essential
      role of vitamins in maintaining the one-carbon transfer cycles. Folate and
      choline are believed to be central methyl donors required for mitochondrial
      protein and nucleic acid synthesis through their active forms, 5
      methyltetrahydrofolate and betaine, respectively. Cobalamin (B12) may assist
      methyltetrahydrofolate in the synthesis of methionine, a cysteine source for
      glutathione biosynthesis. Pyridoxal, pyridoxine and pyridoxamine (B6) seem to be
      involved in the regeneration of tetrahydrofolate into the active methyl-bearing
      form and in glutathione biosynthesis from homocysteine. Other roles of these
      vitamins that are relevant to mitochondrial functions will also be discussed.
      However these roles for B vitamins in cell function are mostly theoretically
      based and still require verification at the cellular level. For instance it is
      still not known what B vitamins are depleted by xenobiotic toxins or which
      cellular targets, metabolic pathways or molecular toxic mechanisms are prevented
      by B vitamins. This review covers the current state of knowledge and suggests
      where this research field is heading so as to better understand the role vitamin
      Bs play in cellular function and intermediary metabolism as well as molecular,
      cellular and clinical consequences of vitamin deficiency. The current
      experimental and clinical evidence that supplementation alleviates deficiency
      symptoms as well as the effectiveness of vitamins as antioxidants will also be
      reviewed.

PMID- 16814760
TI  - Acridine Orange based platinum(II) complexes inducing cytotoxicity and cell cycle
      perturbation in spite of GSTP1 up-regulation.
AB  - A series of new ionic Pt(II) complexes of general formula [Pt(II)(A)n(Cl)(AO)]X
      (A=en, NH3; n=1, 2; X-=BF4-, NO3-, PF6-, CF3SO3-), 1-5, containing Acridine
      Orange (AO) bound to the metal atom through the endocyclic N atom, have been
      tested in human melanoma cells (M14, JR8 and PLF2), human neuroblastoma cell line
      SH-SY5Y and its cis-platin resistant subline SH-SY5Yres. The Pt(II) compounds,
      and in particular complexes 1 and 4, exhibit higher cytotoxic activity at lower
      concentration compared to cis-DDP in melanoma cells, affecting cell growth
      behavior and causing cell cycle perturbation. Moreover, M14 and JR8 cell lines
      were not able to rescue the impairment due to the new Pt(II) complexes since
      perturbation of cell cycle phases and cell proliferation inhibition were found
      after 72 h of recovery time. In order to evaluate whether GSTP1 may play a role
      in chemo-resistance of our melanoma model, we investigated the effect of the
      treatment with these Pt(II) compounds on GSTP1 gene expression. Up-regulation of
      GSTP1, evaluated by Qreal-time PCR was observed after treatment with complexes 1
      and 4, showing that the effect of these Pt(II) compounds is GSTP1 indipendent.
      The lack of resistance of the new Pt(II)-AO complexes and their cytotoxicity,
      cell growth and cell cycle recovery in melanoma cells provide the basis for the
      development of new platinum anticancer compounds, directed to those tumors that
      over express GSTs enzymes.

PMID- 16814761
TI  - Postprandial behavior of plasma squalene and non-cholesterol sterols in men with
      varying cholesterol absorption.
AB  - BACKGROUND: The purpose of this study was to investigate, whether low vs. high
      absorption of cholesterol affects the postprandial lipid clearance (squalene as
      the surrogate marker) and postprandial cholesterol metabolism evaluated with
      plasma levels of cholesterol absorption (cholestanol and plant sterols) and
      synthesis markers (desmosterol and lathosterol). METHODS: Fifteen normo- or
      mildly hypercholesterolemic men were divided into low or high cholesterol
      absorbers on the basis of plasma cholestanol to cholesterol ratio and they
      volunteered to an oral fat load test containing fat 35 g/m(2) body surface.
      RESULTS: Plasma squalene to cholesterol ratio did not differ between the groups
      throughout the postprandial follow-up of 8 h. The level differences in the plasma
      absorption and synthesis markers seen at baseline remained between the groups, so
      that in high absorbers the absorption markers remained high and synthesis markers
      low throughout the postprandial follow-up. The postprandial response curves of
      desmosterol (p<0.05) and lathosterol (p=0.052) to cholestanol decreased linearly
      in the low, but not in the high absorbers. CONCLUSIONS: Low vs. high absorption
      of cholesterol does not affect the first 8-h postprandial lipid clearance. The
      metabolic profile of cholesterol is maintained postprandially. The postprandial
      decrease in cholesterol synthesis differs in low vs. high absorbers especially
      through the desmosterol pathway.

PMID- 16814762
TI  - A prospective cohort study of predictive value of homocysteine in patients with
      type 2 diabetes and coronary artery disease.
AB  - BACKGROUND: Little evidence exists on the role of homocysteine as a predictor of
      mortality in patients with type 2 diabetes. The aim of this study was to
      investigate whether elevated plasma homocysteine levels are independently
      associated with all-cause or cardiovascular mortality in patients with type 2
      diabetes and coronary artery disease. METHODS: This is a prospective cohort study
      that included 507 patients with type 2 diabetes and angiographically proven
      coronary artery disease. Patients were divided into 2 groups according to
      homocysteine level above or below median value (12.4 micromol/L): the high
      homocysteine group (255 patients) and the low homocysteine group (252 patients).
      The primary end-point of the study was all-cause mortality. RESULTS: There were
      103 deaths during a 4-year follow-up: 62 deaths in the high homocysteine group
      and 41 deaths in the low homocysteine group (Kaplan-Meier estimates of mortality
      25.6% and 17.4%, respectively (odds ratio [OR] 1.53, 95% confidence interval [CI]
      1.03-2.27, P=0.031). Sixty-two of 103 deaths (60.2%) were of cardiovascular
      origin: 37 deaths (14.5%) occurred in the high homocysteine group and 25 deaths
      (9.9%) occurred in the low homocysteine group (P=0.115). Cox proportional hazards
      model showed that plasma homocysteine was not an independent correlate of all
      cause (adjusted hazard ratio [HR] 1.10, 95% CI 0.89-1.33; P=0.397 for 5
      micromol/L increase in concentration) or cardiovascular (adjusted HR 1.04, 95% CI
      0.80-1.36, P=0.753, for 5 micromol/L increase in concentration) mortality.
      CONCLUSION: In patients with type 2 diabetes and coronary artery disease,
      elevated level of homocysteine is an associate of increased cardiovascular risk
      but not an independent predictor of cardiovascular mortality.

PMID- 16814763
TI  - Rapid quantitation of lamivudine-resistant mutants in lamivudine treated and
      untreated patients with chronic hepatitis B virus infection.
AB  - BACKGROUND: Long-term lamivudine treatment induces emergence of lamivudine
      resistant hepatitis B virus (HBV) in a significant number of patients with
      chronic HBV infection. Rapid and quantitative methods to determine the percentage
      of lamivudine-resistant mutants in total HBV are important during lamivudine
      therapy. METHODS: We established a quantitative real-time PCR method with
      selective primers and TaqMan probe to detect the percentage of lamivudine
      resistant mutants in total HBV without the need of external DNA standards. This
      percentage was calculated as the PCR efficiency raised to the differences between
      threshold cycle number (DeltaCt) of mutant and control reactions. Clones of the
      HBV polymerase gene containing the different YMDD variants were diluted in series
      and tested. Serum samples from 145 lamivudine-treated and 98 untreated patients
      with chronic hepatitis B virus infection were analyzed using this method and
      compared with DNA sequencing. RESULTS: As little as 0.1% mutant plasmids in 10(6)
      10(9) copies/ml of wild-type plasmids were detected. Among the 145 patients
      treated with lamivudine, 42 of them had mutants with percentages of 5-100%. In
      six discordant results between real-time PCR and DNA sequencing, real-time PCR
      detected mutants with percentages of 5-20%, which were concordant with subclone
      sequencing. Five of 98 lamividine-untreated patients had mutants of 10-20% in
      wild-type virus populations. Compared to DNA sequencing, real-time PCR was fast
      and cost-effective. CONCLUSION: This real-time PCR is a rapid, sensitive and cost
      effective method for relative quantitation of YMDD mutants of HBV.

PMID- 16814764
TI  - Obesity, plasma high sensitivity C-reactive protein levels and insulin resistance
      status among school children in Taiwan.
AB  - OBJECTIVE: To evaluate the degree of obesity and plasma high sensitivity C
      reactive protein (hs-CRP) levels in relation to insulin resistance status among
      school children in Taiwan. METHODS: After multistage sampling, we randomly
      selected 1438 children (701 boys and 737 girls) with the mean age of 13.4 years
      (from 12 to 16) in Taipei in 2003. Anthropometric measures and plasma biochemical
      variables (including lipid profiles, glucose and insulin) were measured using
      standard methods. Plasma hs-CRP levels were measured using nephelometric methods.
      We calculated insulin resistance (IR) index using HOMA methods and further
      calculated a gender-specific insulin resistance syndrome (IRS) summary score by
      adding the quartile ranks from the distribution of systolic blood pressure (SBP),
      triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and insulin
      levels of each children. A high IRS summary score corresponds to higher levels of
      SBP, TG and insulin levels and lower levels of HDL-C. RESULTS: Boys were taller,
      heavier, had larger BMI, glucose, IRS summary score and hs-CRP than girls;
      however, there is no difference in plasma TG, insulin levels, and IR index
      between genders. Plasma hs-CRP levels were positively correlated with
      anthropometric measures, TG, insulin levels, IR index, and IRS summary score and
      negatively correlated with HDL-C. Anthropometric measures, plasma TG, insulin
      levels, IR index and IRS summary score were significantly higher in children with
      higher plasma hs-CRP levels (test for trend p<0.05). After adjustment for age,
      heart rate, smoking and drinking, hs-CRP continued to be positively associated
      with anthropometric variables (weight and BMI), insulin levels, and IR index and
      negatively correlated with HDL-C in both genders. Plasma hs-CRP levels were also
      positively associated with TG and IRS summary score in boys and glucose in girls.
      However, after further adjusting for BMI, the association of hs-CRP on TG,
      insulin levels, IR index and IRS summary score disappeared in boys and on body
      weight, HDL-C, insulin level and IR index disappeared in girls. CONCLUSION:
      Plasma hs-CRP levels are positively related to anthropometric variables, such as
      body weight and BMI, insulin levels, IR index and IRS summary score and
      negatively related to HDL-C in Taiwanese children. Moreover, the degree of body
      fat status (as measured by BMI) plays a more significantly role on insulin
      resistance status than hs-CRP levels among Taiwanese children.

PMID- 16814765
TI  - Reactive oxygen species mediate phorbol ester-stimulated cAMP response in human
      eosinophils.
AB  - Recently, we showed that phorbol 12-myristate 13-acetate (PMA) can cause a
      direct, PKC-dependent, stimulation of intracellular cAMP in human eosinophils.
      Since PMA also stimulates the release of reactive oxygen species in these cells,
      we have investigated whether reactive oxygen species are involved in the cAMP
      response. Provided eosinophils were incubated for <20 min at 37 degrees C before
      stimulation, PMA potently stimulated cAMP generation that surpassed that of
      histamine. Pre-treatment of the cells with the NADPH oxidase inhibitors,
      diphenyleneiodonium (DPI) and apocynin, strongly inhibited the cAMP production
      induced by PMA, but not that induced by histamine. This treatment also strongly
      inhibited the release of superoxide anions (O(2)(-)). The cAMP response was also
      inhibited by pre-treatment with the specific peroxide scavenger, ebselen, but not
      superoxide dismutase, or NG-nitro-l-arginine methyl ester (L-NAME), thus,
      suggesting the possible involvement of a peroxide rather than O(2)(-) or nitric
      oxide (NO). These results reveal a novel involvement of intracellular reactive
      oxygen species in protein kinase C (PKC)-dependent stimulation of cAMP production
      in human eosinophils.

PMID- 16814766
TI  - Multiple mechanisms of hypocholesterolemic action of pactimibe, a novel acyl
      coenzyme A:cholesterol acyltransferase inhibitor.
AB  - Novel acyl-coenzyme A:cholesterol acyltransferase inhibitor pactimibe has been
      evaluated in vivo; it exhibited significant serum cholesterol lowering activities
      in hamsters and monkeys without affecting non-high density lipoprotein
      cholesterol levels. The mechanism of the hypocholesterolemic action of pactimibe
      was examined in normocholesterolemic hamsters in this study. Results with the
      dual-isotope plasma ratio method indicated that pactimibe inhibits cholesterol
      absorption from the intestine, reduces cholesteryl ester formation in the liver,
      and enhances its elimination from the body. The Triton WR-1339 experiment showed
      that pactimibe inhibited secretion of very low density lipoprotein cholesterol
      from the liver. These results suggest that pactimibe is likely to have multiple
      mechanisms of action responsible for its effectiveness in reducing serum
      cholesterol.

PMID- 16814767
TI  - Clonidine inhibits the canine external carotid vasodilatation to capsaicin by
      alpha2A/2C-adrenoceptors.
AB  - Migraine is a disorder associated with increased plasma concentrations of
      calcitonin gene-related peptide (CGRP). CGRP, a neuropeptide released from
      activated trigeminal sensory nerves, dilates cranial blood vessels and transmits
      vascular nociception. Moreover, several antimigraine drugs inhibit the dural
      neurogenic vasodilatation to trigeminal stimulation. Hence, this study
      investigated in anaesthetized dogs the effects of the alpha(2)-adrenoceptor
      agonist, clonidine, on the external carotid vasodilator responses to capsaicin,
      alpha-CGRP and acetylcholine. 1-min intracarotid infusions of capsaicin (10, 18,
      30 and 56 microg/min), alpha-CGRP (0.1, 0.3, 1 and 3 microg/min) and
      acetylcholine (0.01, 0.03, 0.1 and 0.3 microg/min) produced dose-dependent
      increases in external carotid conductance without affecting blood pressure or
      heart rate. Interestingly, the carotid vasodilator responses to capsaicin, but
      not those to alpha-CGRP or acetylcholine, were partially inhibited after
      clonidine (total dose: 24.4 microg/kg, i.v.); in contrast, equivalent volumes of
      saline did not affect the responses to capsaicin, alpha-CGRP or acetylcholine.
      The inhibitory responses to clonidine were antagonized by i.v. administration of
      the alpha(2)-adrenoceptor antagonists rauwolscine (alpha(2A/2B/2C); 300
      microg/kg), BRL44408 (alpha(2A); 1000 microg/kg) or MK912 (alpha(2C); 100 and 300
      microg/kg), but not by imiloxan (alpha(2B); 1000 microg/kg). These results
      suggest that clonidine inhibits the external carotid vasodilator responses to
      capsaicin by peripheral trigeminovascular and/or central mechanisms; this
      inhibitory response to clonidine seems to be predominantly mediated by alpha(2A)
      adrenoceptors and, to a much lesser extent, by alpha(2C)-adrenoceptors.

PMID- 16814768
TI  - Altered caveolin-3 expression disrupts PI(3) kinase signaling leading to death of
      cultured muscle cells.
AB  - Caveolae and their coat proteins, caveolins, co-ordinate multiple signaling
      pathways. Caveolin-3 is a muscle-specific caveolin isoform that is deficient in
      limb girdle muscular dystrophy type 1 C (LGMD1C). Paradoxically, overexpression
      of this protein also causes muscle degeneration in vivo. We hypothesize that
      altered membrane expression of caveolin-3 in muscle cells causes a degenerative
      phenotype by disrupting the co-ordination of signaling pathways that are critical
      to the maintenance of cell survival. Here, we show for the first time that, in
      normal muscle cells subjected to oxidative stress, the phosphatidylinositol (3)
      kinase (PI(3) kinase)-associated proteins PDK1 and Akt associate with caveolae
      where they bind to caveolin-3, and that normal activation of this pathway
      promotes cell survival. Either increased or decreased expression of caveolin-3 at
      the membrane caused an increased susceptibility to oxidative stress, and myotube
      survival was markedly improved by PI(3) kinase inhibition. This occurred
      concomitantly with altered phosphorylation of the pro-apoptotic proteins GSK3beta
      and Bad, despite normal levels of Akt activation. Taken together, our results
      demonstrate that altered caveolin-3 expression can change the outcome of PI(3)
      kinase activation from cell survival to cell death. These findings indicate that
      normal expression and localization of caveolin-3 are required to appropriately co
      ordinate PI(3) kinase/Akt-mediated cell survival signaling, and suggest that this
      pathway may be an effective therapeutic target for the treatment of muscular
      dystrophies associated with caveolin-3 mutations.

PMID- 16814769
TI  - JNK phosphorylation of paxillin, acting through the Rac1 and Cdc42 signaling
      cascade, mediates neurite extension in N1E-115 cells.
AB  - Neurons extend neurites from the cell body before formation of the polarized
      processes of an axon and dendrites. Neurite outgrowth involves remodeling of the
      cytoskeletal components, which are initially regulated by small GTPases of the
      Rho family. Here we show that c-Jun N-terminal kinase (JNK), which is controlled
      by Rho GTPases Rac1 and Cdc42, is activated following neurite extension in mouse
      N1E-115 neuroblastoma cells as a model. The extension is inhibited by JNK
      inhibitors (SP600125 and the small JNK-binding peptide) and Clostridium difficile
      Toxin B, the inhibitor for Rho GTPases. Additionally, paxillin, the
      multifunctional focal adhesion protein, is phosphorylated at Ser 178 by
      upregulation of the Rac1/Cdc42/JNK cascade. Conversely, transfection of the
      paxillin construct harboring the Ser 178-to-Ala mutation into cells inhibits
      neurite extension. Taken together, these results suggest the novel role of the
      Rac1/Cdc42/JNK signaling cascade in neurite extension and indicate that the
      downstream target paxillin may be one of the convergent points of various
      signaling pathways underlying neurite extension.

PMID- 16814770
TI  - Postural development in rats.
AB  - Mammals adopt a limited number of postures during their day-to-day activities.
      These stereotyped skeletal configurations are functionally adequate and limit the
      number of degrees of freedom to be controlled by the central nervous system. The
      temporal pattern of emergence of these configurations in altricial mammals is
      unknown. We therefore carried out an X-ray study in unrestrained rats from birth
      (P0) until postnatal day 23 (P23). The X-rays showed that many of the skeletal
      configurations described in adult rodents were already present at birth. By
      contrast, limb placement changed abruptly at around P10. These skeletal
      configurations, observed in anesthetized pups, required the maintenance of
      precise motor control. On the other hand, motor control continued to mature, as
      shown by progressive changes in resting posture and head movements from P0 to
      P23. We suggest that a few innate skeletal configurations provide the necessary
      frames of reference for the gradual construction of an adult motor repertoire in
      altricial mammals, such as the rat. The apparent absence of a requirement for
      external sensorial cues in the maturation of this repertoire may account for the
      maturation of postural and motor control in utero in precocial mammals (Muir et
      al., 2000 for a review on the locomotor behavior of altricial and precocial
      animals).

PMID- 16814771
TI  - Functional and morphological effects of NG2 proteoglycan deletion on hippocampal
      neurogenesis.
AB  - NG2-expressing cells are the largest proliferating cell population in the adult
      central nervous system. The function of NG2 proteoglycan or NG2-expressing cells
      in the adult brain, however, is unknown. So far, NG2-positive cells are thought
      to be mainly oligodendrocyte precursor cells. This view was recently challenged
      when NG2+/CNP-EGFP-positive cells were identified as multipotent progenitor cells
      in the postnatal and adult CNS (e.g., [Belachew, S., Chittajallu, R., Aguirre,
      A.A., Yuan, X., Kirby, M., Anderson, S., Gallo, V., 2003. Postnatal NG2
      proteoglycan-expressing progenitor cells are intrinsically multipotent and
      generate functional neurons. J. Cell Biol. 161, 169-186]). In addition, purified
      NG2-expressing progenitor cells, were shown to differentiate into neurons and
      astrocytes in vitro [Sellers, D.L., Horner, P.J., 2005. Instructive niches:
      environmental instructions that confound NG2 proteoglycan expression and the fate
      restriction of CNS progenitors J. Anat. 207, 727-734]. In this study, we focus on
      the influence of NG2 ablation on neurogenesis in the hippocampus, where putative
      multipotent NG2-positive cells reside, and on hippocampus-dependent behavior
      using NG2 knockout mice. Using the thymidine analogue bromodeoxyuridine (BrdU) to
      label dividing cells in vivo we show that the number of BrdU-positive cells was
      unchanged in the hippocampus of NG2 knockout mice 1 day after a series of BrdU
      injections. This finding suggests that the proliferation rate of hippocampal
      progenitor cells is not influenced by NG2. A few BrdU-positive cells were found
      in deeper layers of the granule zone 1 day after a series of BrdU injections,
      which is different from the wild type. The presence and the phenotype of newborn
      hippocampal cells were studied 4 weeks after a series of BrdU injections. The
      survival and differentiation of BrdU-positive cells in NG2 knockout hippocampus
      did not significantly differ from wild-type mice. Concurrently, the water maze
      task did not reveal obvious differences compared to wild-type animals. These
      results suggest that the null mutation for NG2 does not influence adult
      hippocampal neurogenesis or hippocampal-dependent behavioral tasks.

PMID- 16814772
TI  - Neuroprotective effect of hyperbaric oxygen therapy monitored by MR-imaging after
      embolic stroke in rats.
AB  - The potential neuroprotective effects of hyperbaric oxygen (HBO) were tested in
      an embolic model of focal cerebral ischemia with partially spontaneous
      reperfusion. Rats (n = 10) were subjected to embolic middle cerebral artery
      occlusion (MCAO) and diffusion weighted MRI (DWI) was performed at baseline, 1,
      3, and 6 h after MCAO to determine the ADC viability threshold yielding the
      lesion volumes that best approximated the 2,3,5-triphenyltetrazolium chloride
      (TTC) infarct volumes at 24 h (experiment 1). For assessment of neuroprotective
      effects, rats were treated with 100% oxygen at 2.5 atmospheres absolute (ATA, n =
      15) or normobaric room air (n = 15) for 60 min beginning 180 min after MCAO
      (experiment 2). DWI-, perfusion (PWI)- and T2-weighted MRI (T2WI) started within
      0.5 h after MCAO and was continued 5 h, 24 h (PWI and T2WI only), and 168 h (T2WI
      only). Infarct volume was calculated based on TTC-staining at 24 h (experiment 1)
      or 168 h (experiment 2) post-MCAO. ADC-lesion evolution was maximal between 3 and
      6 h. In experiment 2, the relative regional cerebral blood volume (rCBV) of both
      groups showed similar incomplete spontaneous reperfusion in the ischemic core.
      HBO reduced infarct volume to 145.3 +/- 39.6 mm3 vs. 202.5 +/- 58.3 mm3 (control,
      P = 0.029). As shown by MRI and TTC, HBO treatment demonstrated significant
      neuroprotection at 5 h after embolic focal cerebral ischemia that lasted for 168
      h.

PMID- 16814773
TI  - Restricted ablative lesions in motor portions of GPi in primates produce
      extensive loss of motor-related neurons and degeneration of the lenticular
      fasciculus.
AB  - Deep brain stimulation (DBS) of the internal pallidum (GPi) and the subthalamic
      nucleus and to a lesser extent, ablative lesioning, are broadly utilized to treat
      patients with medically intractable Parkinson's disease and other movement
      disorders. Beneficial outcomes however are not uniform and adverse cognitive and
      behavioral are significant risks. Surgical outcomes of GPi surgeries might be
      improved by approaches that better account for the course of motor and non-motor
      pallidothalamic projections. Although several studies, including our own tracer
      investigations, suggest that motor projections from GPi principally form the
      lenticular fasciculus and non-motor projections primarily contribute to the ansa
      lenticularis, other schemes have perpetuated. Presently, to corroborate the
      course of pallidothalamic projections and to assess the feasibility of
      selectively targeting the motor circuit of GPi, radiofrequency lesions were
      placed in the motor portion of GPi in monkeys. Degenerating pallidothalamic
      fibers were visualized with amino cupric staining techniques and regional cell
      counts in GPi were compared with control hemispheres. Lesions restricted to
      posterior motor portions of GPi produced selective degeneration of LF and only
      damaged AL if the lesions extended more anteriorly. Marked secondary neuronal
      loss occurred well beyond the principal lesions but was mainly confined to the
      posterolateral motor region of GPi. These findings corroborate the original
      pallidothalamic outflow scheme proposed by Ranson and Ranson. Conceivably, a
      restrictive lesion or a DBS probe could be placed in the centroposterior portion
      of GPi to selectively target both local motor-related neurons and traversing
      pallidothalamic fibers originating from more posterior and lateral motor regions.

PMID- 16814774
TI  - Long-term video-EEG recordings following transient unilateral middle cerebral and
      common carotid artery occlusion in Long-Evans rats.
AB  - The mechanisms of injured brain that establish poststroke seizures and epilepsy
      are not well understood, largely because animal modeling of these phenomena has
      had limited development. We studied the electrobehavioral properties of 2.5-month
      old male Long-Evans rats by video-electroencephalogram (EEG) recordings during
      the 6 months following sham operation or lesioning by transient unilateral middle
      cerebral artery (MCA) and common carotid artery (CCA) occlusion (MCA/CCAO). The
      main findings of this study were: (1) control animals demonstrated interictal
      focal or restricted bilateral 7-8 Hz spike-wave discharges (SWDs) lasting 1-2 s
      without behavioral change and ictal generalized 7-8 Hz SWDs (absence seizures),
      which were prolonged, frequent, and associated with motor arrest of the animal;
      (2) lesioned animals demonstrated cortical infarction associated with interictal
      SWDs similar to controls, except that focal discharges were more numerous
      relative to bilateral discharges, and ictal SWDs, which were of shorter duration
      and less frequent than those of controls; (3) lesioned animals demonstrated
      decreased hemispheric and regional spectral power at approximately 7 and 15 Hz
      compared with controls, directly related to the reduced occurrence of ictal SWDs;
      and (4) lesioning did not independently generate either focal or generalized
      epileptic seizures. These studies demonstrate distinct electrobehavioral
      properties of Long-Evans rats lesioned by MCA/CCAO as juveniles and monitored by
      video-EEG recordings during young adulthood but fail to provide evidence of
      poststroke seizures or epilepsy.

PMID- 16814775
TI  - Contingent and non-contingent effects of heroin on mu-opioid receptor-containing
      ventral tegmental area GABA neurons.
AB  - Opiate activation of mu-opioid receptors (muORs) in the ventral tegmental area
      (VTA) modulates gamma-aminobutyric acid (GABA) neurotransmission within the
      mesocorticolimbic dopamine (DA) reward system. We combined in vivo extracellular
      electrophysiological recordings in anesthetized and freely behaving rats with
      intracellular Neurobiotin filling and immunocytochemistry to characterize the
      effects of opiates on VTA GABA neurons, evaluate their discharge activity during
      opiate self-administration, and identify the cellular sites for opiate
      activation. We identified a subpopulation of VTA GABA neurons that was
      characterized by location, spike discharge profile, activation by
      microelectrophoretic DA, and response to internal capsule (IC) stimulation.
      Systemic administration of heroin or microelectrophoretic application of the
      selective muOR agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) reduced VTA
      GABA neuron firing rate (heroin IC(50) = 0.35 mg/kg) and was blocked by the muOR
      antagonist naloxone. Heroin also reduced IC-evoked post-stimulus spike
      discharges, a manifestation of gap-junction-mediated electrical coupling between
      VTA GABA neurons. The baseline firing rate of VTA GABA neurons significantly
      increased (239%) following the acquisition of heroin self-administration behavior
      and transiently increased during each response for heroin (105%), but decreased
      (49%) following heroin, similar to non-contingent heroin. Electrophysiologically
      characterized VTA GABA neurons were filled with Neurobiotin and labeled dendrites
      contained plasmalemmal muOR immunoreactivity. Dually labeled muOR dendrites
      contained dendrodendritic appositions characteristic of gap junctions. These
      findings indicate that inhibition of this population of GABAergic neurons by
      opiates acting on dendritic muORs has implications for modulation of electrical
      coupling between VTA GABA neurons and dopamine (DA) neurotransmission in the VTA
      and terminal field regions.

PMID- 16814776
TI  - Leishmania amazonensis: characterization of an ecto-phosphatase activity.
AB  - We have characterized a phosphatase activity present on the external surface of
      Leishmania amazonensis, using intact living parasites. This enzyme hydrolyzes the
      substrate p-nitrophenylphosphate (p-NPP) at the rate of 25.70+/-1.17 nmol Pi x h(
      1) x 10(-7)cells. The dependence on p-NPP concentration shows a normal Michaelis
      Menten kinetics for this ecto-phosphatase activity present a V(max) of 31.93+/
      3.04 nmol Pi x h(-1) x 10(-7)cells and apparent K(m) of 1.78+/-0.32 mM. Inorganic
      phosphate inhibited the ecto-phoshatase activity in a dose-dependent manner with
      the K(i) value of 2.60 mM. Experiments using classical inhibitor of acid
      phosphatase, such as ammonium molybdate, as well as inhibitors of phosphotyrosine
      phosphatase, such as sodium orthovanadate and [potassiumbisperoxo(1,10
      phenanthroline)oxovanadate(V)] (bpV-PHEN), inhibited the ecto-phosphatase
      activity, with the K(i) values of 0.33 microM, 0.36 microM and 0.25 microM,
      respectively. Zinc chloride, another classical phosphotyrosine phosphatase
      inhibitor, also inhibited the ecto-phosphatase activity in a dose-dependent
      manner with K(i) 2.62 mM. Zinc inhibition was reversed by incubation with reduced
      glutathione (GSH) and cysteine, but not serine, showing that cysteine residues
      are important for enzymatic activity. Promastigote growth in a medium
      supplemented with 1mM sodium orthovanadate was completely inhibited as compared
      to the control medium. Taken together, these results suggest that L. amazonensis
      express a phosphohydrolase ectoenzyme with phosphotyrosine phosphatase activity.

PMID- 16814777
TI  - Protein tyrosine phosphatase receptor type Z is inactivated by ligand-induced
      oligomerization.
AB  - Receptor-type protein tyrosine phosphatases (RPTPs) are considered to transduce
      extracellular signals across the membrane through changes in their PTP activity,
      however, our understanding of the regulatory mechanism is still limited. Here, we
      show that pleiotrophin (PTN), a natural ligand for protein tyrosine phosphatase
      receptor type Z (Ptprz) (also called PTPzeta/RPTPbeta), inactivates Ptprz through
      oligomerization and increases the tyrosine phosphorylation of substrates for
      Ptprz, G protein-coupled receptor kinase-interactor 1 (Git1) and membrane
      associated guanylate kinase, WW and PDZ domain containing 1 (Magi1).
      Oligomerization of Ptprz by an artificial dimerizer or polyclonal antibodies
      against its extracellular region also leads to inactivation, indicating that
      Ptprz is active in the monomeric form and inactivated by ligand-induced
      oligomerization.

PMID- 16814778
TI  - Properties of the [NiFe]-hydrogenase maturation protein HypD.
AB  - A mutational screen of amino acid residues of hydrogenase maturation protein HypD
      from Escherichia coli disclosed that seven conserved cysteine residues located in
      three different motifs in HypD are essential. Evidence is presented for potential
      functions of these motifs in the maturation process.

PMID- 16814780
TI  - Amyloid excess in Alzheimer's disease: what is cholesterol to be blamed for?
AB  - A link between alterations in cholesterol homeostasis and Alzheimer's disease
      (AD) is nowadays widely accepted. However, the molecular mechanism/s underlying
      such link remain unclear. Numerous experimental evidences support the view that
      changes in neuronal membrane cholesterol levels and/or subcellular distribution
      determine the aberrant accumulation of the amyloid peptide in the disease. Still,
      this view comes from rather contradictory data supporting the existence of either
      high or low brain cholesterol content. This is of particular concern considering
      that therapeutical strategies aimed to reduce cholesterol levels are already
      being tested in humans. Here, we review the molecular mechanisms proposed and
      discuss the perspectives they open.

PMID- 16814779
TI  - Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a
      novel brain-specific receptor-like protein family.
AB  - By DNA cloning, we have identified the BSRP (brain-specific receptor-like
      proteins) family of three members in mammalian genomes. BSRPs were predominantly
      expressed in the soma and dendrites of neurons and localized in the endoplasmic
      reticulum (ER). Expression levels of BSRPs seemed to fluctuate greatly during
      postnatal cerebellar maturation. Triple-knockout mice lacking BSRP members
      exhibited motor discoordination, and Purkinje cells (PCs) were often innervated
      by multiple climbing fibers with different neuronal origins in the mutant
      cerebellum. Moreover, the phosphorylation levels of protein kinase Calpha
      (PKCalpha) were significantly downregulated in the mutant cerebellum. Because
      cerebellar maturation and plasticity require metabotropic glutamate receptor
      signaling and resulting PKC activation, BSRPs are likely involved in ER functions
      supporting PKCalpha activation in PCs.

PMID- 16814781
TI  - Oxygen binding and NO scavenging properties of truncated hemoglobin, HbN, of
      Mycobacterium smegmatis.
AB  - Unraveling of microbial genome data has indicated that two distantly related
      truncated hemoglobins (trHbs), HbN and HbO, might occur in many species of slow
      growing pathogenic mycobacteria. Involvement of HbN in bacterial defense against
      NO toxicity and nitrosative stress has been proposed. A gene, encoding a putative
      HbN homolog with conserved features of typical trHbs, has been identified within
      the genome sequence of fast-growing mycobacterium, Mycobacterium smegmatis.
      Sequence analysis of M. smegmatis HbN indicated that it is relatively smaller in
      size and lacks N-terminal pre-A region, carrying 12-residue polar sequence motif
      that is present in HbN of M. tuberculosis. HbN encoding gene of M. smegmatis was
      expressed in E. coli as a 12.8kD homodimeric heme protein that binds oxygen
      reversibly with high affinity (P50 approximately 0.081 mm Hg) and autooxidizes
      faster than M. tuberculosis HbN. The circular dichroism spectra indicate that HbN
      of M. smegmatis and M. tuberculosis are structurally similar. Interestingly, an
      hmp mutant of E. coli, unable to metabolize nitric oxide, exhibited very low NO
      uptake activity in the presence of M. smegmatis HbN as compared to HbN of M.
      tuberculosis. On the basis of cellular heme content, specific nitric oxide
      dioxygenase (NOD) activity of M. smegmatis HbN was nearly one-third of that from
      M. tuberculosis. Additionally, the hmp mutant of E. coli, carrying M. smegmatis
      HbN, exhibited nearly 10-fold lower cell survival under nitrosative stress and
      nitrite derived reactive nitrogen species as compared to the isogenic strain
      harboring HbN of M. tuberculosis. Taken together, these results suggest that NO
      metabolizing activity and protection provided by M. smegmatis HbN against
      toxicity of NO and reactive nitrogen is significantly lower than HbN of M.
      tuberculosis. The lower efficiency of M. smegmatis HbN for NO detoxification as
      compared to M. tuberculosis HbN might be related to different level of NO
      exposure and nitrosative stress faced by these mycobacteria during their cellular
      metabolism.

PMID- 16814782
TI  - Coffee inhibits the reactivation of glucocorticoids by 11beta-hydroxysteroid
      dehydrogenase type 1: a glucocorticoid connection in the anti-diabetic action of
      coffee?
AB  - Recent epidemiological studies demonstrated a beneficial effect of coffee
      consumption for the prevention of type 2 diabetes, however, the underlying
      mechanisms remained unknown. We demonstrate that coffee extract, corresponding to
      an Italian Espresso, inhibits recombinant and endogenous 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) activity. The inhibitory component is heat
      stable with considerable polarity. Coffee extract blocked 11beta-HSD1-dependent
      cortisol formation, prevented the subsequent nuclear translocation of the
      glucocorticoid receptor and abolished glucocorticoid-induced expression of the
      key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. We suggest that at
      least part of the anti-diabetic effects of coffee consumption is due to
      inhibition of 11beta-HSD1-dependent glucocorticoid reactivation.

PMID- 16814783
TI  - Overexpression of E2A proteins induces epithelial-mesenchymal transition in human
      renal proximal tubular epithelial cells suggesting a potential role in renal
      fibrosis.
AB  - Epithelial-mesenchymal transition (EMT), a process whereby renal tubular
      epithelial cells lose phenotype and gain fibroblast-like characteristics, has
      been demonstrated to contribute significantly to the development of renal
      fibrosis. The immunosuppressant cyclosporine A (CsA) has been shown to induce
      renal fibrosis, a major complication of CsA therapy. The mechanisms that drive
      CsA-induced fibrosis remain undefined, however, CsA has been demonstrated to
      induce EMT in human renal proximal tubular epithelial cells (RPTEC). E2A
      transcription factors were identified as being upregulated by CsA treatment. To
      further examine the role of E2A proteins in EMT, E12 and E47 were overexpressed,
      alone and in combination, in human RPTEC. Both E12 and E47 elicited EMT effects
      on tubular epithelial cells with E47 more potent in inducing the fibroblast-like
      phenotype. These results indicate the important role of the E2A gene products in
      the progression of CsA-induced EMT and provide novel insights into CsA-induced
      renal fibrosis.

PMID- 16814784
TI  - Changes in subcellular localization of fructose 1,6-bisphosphatase during
      differentiation of isolated muscle satellite cells.
AB  - Subcellular localization of FBPase, a regulatory enzyme of glyconeogenesis, was
      examined inside dividing and differentiating satellite cells from rat muscle. In
      dividing myoblasts, FBPase was located in cytosol and nuclei. When divisions
      ceased, FBPase became restricted to the cytosolic compartment and finally was
      found to associate with the Z-lines, as in adult muscle. Moreover, a 12-fold
      decrease was observed in the number of FBPase-positive nuclei associated with
      muscle fibres of adult rat, as compared with young muscle, possibly reflecting
      the reduction in number of active satellite cells during muscle maturation. The
      data might suggest that FBPase participates in some nuclear processes during
      development and regeneration of skeletal muscle.

PMID- 16814785
TI  - Seasonal and individual variation in response to GnRH challenge in male dark-eyed
      juncos (Junco hyemalis).
AB  - Concentrations of gonadal steroids such as testosterone (T) often vary widely in
      natural populations, but the causes and particularly the consistency of this
      variation is relatively unexplored. In breeding males of a wild population of the
      dark-eyed junco (Junco hyemalis), we investigated seasonal and individual
      variation in circulating T during two breeding seasons by measuring the
      responsiveness of the HPG axis to a standardized injection of gonadotropin
      releasing hormone (GnRH). Individuals were bled prior to and 30min after
      injection. Pre- and post-challenge levels of T were measured using EIA. Many
      subjects were sampled repeatedly across multiple breeding stages. Plasma T
      concentrations nearly doubled in response to GnRH during early spring, but showed
      significantly smaller increases in later breeding stages. When controlling for
      seasonal variation in response to challenge, we also found repeatable differences
      among individuals, indicating individual consistency in the release of T in
      response to a standardized stimulus. These seasonal and individual differences
      may arise from comparable variation in responsiveness of the pituitary or a
      decline in gonadal sensitivity to downstream gonadotropins. In contrast, pre
      challenge T showed almost no seasonal changes and did not differ consistently
      among individuals. To our knowledge, this is the first demonstration of
      individual repeatability of short-term hormonal changes in a wild population.
      Such repeatability suggests that hormonal plasticity might evolve in response to
      changing selection pressures.

PMID- 16814786
TI  - Hormonal control of birth behavior in the Tasmanian devil Sarcophilus harrisii.
AB  - In a number of marsupial species, females exhibit characteristic, stereotyped
      parturient behavior that facilitates the passage of the neonates to the pouch. In
      macropodids, this parturient behavior can be induced in non-pregnant females and
      males by treatment with either prostaglandin F2alpha (PGF2alpha) or oxytocin
      (OT). This study investigated the effects of PGF2alpha and OT on behavior of
      Tasmanian devils. Animals tended to sit or lie down quickly, with little
      vocalization, after treatment with PGF2alpha or OT, while after saline, the
      animals remained alert, seldom sat, and frequently vocalized. Hormone treatment
      caused increased respiration. Urogenital and pouch grooming, a characteristic
      element of parturient behavior in macropodids, was seen in only one devil after
      hormone treatment. However, no pouch or urogenital grooming was seen in videotape
      of a devil giving birth, so this may not be a feature of parturient behavior in
      this species. Overall behavior of males and females was very similar suggesting
      that the behavioral effects observed may be due to direct neural action of
      PGF2alpha or OT, rather than an indirect response to uterine or vaginal
      contractions caused by the hormones. This study is the first to demonstrate that
      OT results in PGF2alpha secretion as PGFM levels rose after OT injection.

PMID- 16814787
TI  - Epidemiology of adult fractures: A review.
AB  - The epidemiology of adult fractures is changing quickly. An analysis of 5953
      fractures reviewed in a single orthopaedic trauma unit in 2000 showed that there
      are eight different fracture distribution curves into which all fractures can be
      placed. Only two fracture curves involve predominantly young patients; the other
      six show an increased incidence of fractures in older patients. It is popularly
      assumed that osteoporotic fractures are mainly seen in the thoracolumbar spine,
      proximal femur, proximal humerus and distal radius, but analysis of the data
      indicates that 14 different fractures should now be considered to be potentially
      osteoporotic. About 30% of fractures in men, 66% of fractures in women and 70% of
      inpatient fractures are potentially osteoporotic.

PMID- 16814788
TI  - Intramedullary nailing for open fractures of the femoral shaft: evaluation of
      contributing factors on deep infection and non-union using multivariate analysis
      [Injury 2005;36:1085-93].

PMID- 16814789
TI  - Evaluating the Theory of Planned Behavior to explain intention to engage in
      premarital sex amongst Korean college students: a questionnaire survey.
AB  - BACKGROUND: To reduce risky adolescent sexual behavior, education programs must
      be tailored to specific cultures and stage of adolescence. OBJECTIVES: This study
      describes the self-reported sexual behavior of Korean college students and
      examines the efficiency of the Theory of Planned Behavior (TpB) in explaining
      intention of engaging in premarital sex in order to provide insights for a
      potential sex education program designed to reduce risky sexual behavior. DESIGN:
      A cross-sectional, correlational design using an exploratory survey method was
      used. PARTICIPANTS: Participants were recruited from a university in Korea with a
      flyer posted at the entrance of the student health service center, and self
      referral in 2004. Male and female unmarried college students aged 18 to 25 were
      included. Foreign students and students with visible physical problems were
      excluded. Three hundred and twenty of 550 students returned the questionnaire
      packets. Final data analysis included 298 students after deleting incomplete
      data. METHODS: Participants completed six questionnaires: (1) Background and
      Sexual Behavior Questionnaire, including items related to perceived risk of
      sexual behavior, (2) Parent-Adolescent Communication Scale, and four scales
      related to TpB construct: (3) modified Premarital Sexual Attitude Scale, (4)
      Referent group Approval of Sex Behavior Scale, (5) Sexual Abstinence Efficacy
      Scale and (6) modified version of Doswell's Intention of Sexual Behavior Scale.
      RESULTS: Premarital sexual attitude, abstinence self-efficacy and referent group
      norms were significant predictors of intention of premarital sex for male
      students with a large effect, but only attitude and norms predicted intention of
      premarital sex for female students. CONCLUSION: The TpB may be an effective
      theory to guide the development of theory-driven sexual abstinence interventions
      to reduce risky sexual behavior for Korean males, while the Theory of Reasoned
      Action may be an effective theory for Korean females.

PMID- 16814790
TI  - Identification and characterisation of a leucine aminopeptidase from the hard
      tick Haemaphysalis longicornis.
AB  - Aminopeptidases responsible for blood digestion have yet to be identified in
      haematophagous ticks. We report here the cloning and molecular characterisation
      of a cDNA encoding leucine aminopeptidase, a member of the M17 cytosolic
      aminopeptidase family, from the hard tick Haemaphysalis longicornis (HlLAP).
      Endogenous HlLAP was detected in the soluble fraction of adult tick extracts by
      immunoblotting. Immunohistochemical studies demonstrated that endogenous HlLAP
      expression mainly took place in the cytosol of midgut epithelial cells.
      Furthermore, expression of HlLAP was induced by a blood-feeding process. A
      functional recombinant HlLAP expressed in Escherichia coli efficiently hydrolyses
      synthetic substrates for aminopeptidase, a leucyl (with the Km value 0.19 +/-
      0.011 mM and Vmax value 157.2 +/- 3.17 nmol/min/mgprotein) and a methionyl
      substrate (with the Km value 0.12+/-0.0052 mM and Vmax value 171.9 +/- 2.31
      nmol/min/mgprotein). Enzyme activity was found to be optimum at pH 8 and 35
      degrees C. The recombinant HlLAP enzyme activity was strongly dependent on metal
      divalent cations, Mn2+, and was inhibited by bestatin. These results indicate
      that HlLAP play an important role for host's blood digestion process.

PMID- 16814791
TI  - Increased gene expression of liver SREBP-2 in experimental chronic renal failure.
AB  - Sterol regulatory element-binding protein-2 (SREBP-2) is a transcription factor
      regarded as the main regulator of cholesterol homeostasis. Therefore, increased
      level of SREBP-2 could be responsible for hypercholesterolemia, which is observed
      in experimental chronic renal failure (CRF). This study was designed primary to
      evaluate the impact of experimental CRF (5/6 nephrectomy model) on rat liver
      SREBP-2 gene expression. In CRF rats, a twofold increase in SREBP-2 mRNA level,
      as well as in mature SREBP-2 protein abundance was found, when compared to
      control animals. It was associated with enhanced activity and mRNA abundance of
      liver HMG-CoA reductase, a rate-limiting enzyme for cholesterol biosynthesis. A
      twofold increase in liver cholesterologenesis rate was also noted. We conclude
      that experimental CRF is associated with increased liver SREBP-2 gene expression.
      This is probably the cause for enhanced HMG-CoA reductase gene expression and,
      consequently, for increase in liver cholesterol synthesis in CRF rats. Despite
      increased SREBP-2 gene expression we found LDL-receptor mRNA level to be lower
      than in controls, suggesting SREBP-2 independent mechanisms of LDL-receptor
      transcriptional regulation in CRF rats. Enhanced cholesterol synthesis and
      decreased LDL-receptor mRNA level are probably responsible for an almost fourfold
      increase in serum cholesterol concentration in CRF rats.

PMID- 16814792
TI  - Low-magnitude mechanical signals that stimulate bone formation in the
      ovariectomized rat are dependent on the applied frequency but not on the strain
      magnitude.
AB  - There is growing evidence that extremely small mechanical signals, if applied at
      a sufficiently high frequency, can serve as anabolic signals to bone tissue. To
      determine if the responsiveness of bone to low-magnitude, high-frequency
      parameters is modulated by endocrine imbalance, ovariectomized (OVX) Sprague
      Dawley rats were subjected to whole body vibrations (WBV, 0.15 g) at 45 Hz (n=6)
      or 90 Hz (n=6) for 10 min/day, and compared to OVX age-matched controls (n=6).
      Five additional rats were used, in vivo, to establish the induced bone surface
      strain magnitudes (and strain rates). Following a 28 d protocol, bone formation
      rates in the metaphysis of the proximal tibia were 159% greater in 90 Hz rats
      when compared to age-matched controls, but 45 Hz rats were not significantly
      different from controls. Bone morphology of 90 Hz rats indicated significantly
      greater trabecular bone volume (22% and 25%) and thicker trabeculae (11% and 12%)
      over either controls or 45 Hz rats in the epiphysis of the distal femur,
      respectively. Despite the enhanced sensitivity of the skeleton towards the 90 Hz
      signal, the strain magnitudes and strain rates induced by this frequency were
      significantly lower than during 45 Hz vibration, suggesting that factors other
      than matrix strain are driving the anabolic response. Ideally, such mechanical
      signals represent a non-pharmacologic means of controlling bone mass and
      morphology in spite of systemic pressures for bone resorption.

PMID- 16814793
TI  - New approach based on solid-phase microextraction to estimate
      polydimethylsiloxane fibre coating-water distribution coefficients for brominated
      flame retardants.
AB  - A depletion solid-phase microextraction (SPME) method based on multiple SPME
      extraction was applied to estimate fibre coating-water distribution constants
      (Kfs) of brominated flame retardants. Several polybrominated diphenyl ethers
      (PBDEs) including compounds present in the commercial mixture "Pentamix", and two
      polybrominated biphenyls (PBBs) were considered as target analytes. One hundred
      micrometer poly(dimethylsiloxane) (PDMS) coating fibre was selected to estimate
      partition coefficients. SPME kinetics studies at 25 and 100 degrees C were
      performed. Kfs values obtained at both temperatures for brominated flame
      retardants were compared with the corresponding octanol-water partition
      coefficients (Kow) values found in literature. A linear log-log relationship
      between Kow with Kfs was found. To the best of our knowledge, this is the first
      study where brominated flame retardants Kfs values are estimated.

PMID- 16814794
TI  - Equilibrium theory based design of simulated moving bed processes for a
      generalized Langmuir isotherm.
AB  - In the frame of the local equilibrium theory of chromatography, design criteria
      for complete separation of binary mixtures in simulated moving bed (SMB)
      separations are developed, presented and discussed. These apply to systems, whose
      retention behavior is characterized by a generalized Langmuir isotherm. By
      allowing for negative terms in the denominator of the classical Langmuir
      isotherm, this newly introduced adsorption model captures a broad class of
      competitive or synergistic adsorption, including anti-Langmuir behavior for both
      adsorbates, and mixed cases where one species behaves in a Lagmuirian and the
      other in an anti-Langmuirian manner. By extending classical equilibrium theory
      results for the binary Langmuir isotherm, and by generalizing the approach
      followed earlier to derive SMB design criteria for the binary and multi-component
      Langmuir isotherm, exact algebraic equations for the boundary of the complete
      separation region in the operating parameter space are derived for all possible
      generalized Langmuir isotherm. The effect of changing feed composition on the
      shape of the complete separation region and on the position of the optimal
      operating point is analyzed and discussed.

PMID- 16814795
TI  - On-line pervaporation-capillary electrophoresis for the determination of volatile
      analytes in food slurries.
AB  - Pervaporation has been coupled on-line to capillary electrophoresis (CE) by a
      flow injection manifold and the replenishment system of the CE instrument. The
      approach allows volatile analytes to be removed, derivatisated and injected into
      the capillary meanwhile the sample matrix remains in the pervaporator. Acetone
      and four aldehydes (namely: formaldehyde, acetaldehyde, hexenal, 2-trans-hexenal)
      have been simultaneously determined in slurries samples by this approach. The
      detection limits (LOD) ranged between 0.1 and 0.6 microg/ml, the quantification
      limits between 0.5 and 2.0 microg/ml and the linear dynamic ranges between the
      limit of quantitation and 150 microg/ml. The precision, expressed as relative
      standard deviation (RSD), ranged between 0.76 and 4.21% for repeatability and
      between 1.12 and 4.78% for within laboratory intermediary precision. The errors
      involved in the analysis of the target analytes--expressed as RSD for all
      compounds--ranged between 0.13 and 4.87%. The optimal pervaporation time and that
      necessary for the individual separation/detection of the target analytes are 15
      and 10 min, respectively. The analysis frequency is 4 h(-1). The accuracy of the
      method and potential matrix effects were established by analysing spiked samples.
      Recoveries between 96.12 and 105.67% were obtained. The proposed method was
      applied to 10 samples with different solid contents (namely, such yoghurt, juice
      and yoghurt-juice mixtures).

PMID- 16814796
TI  - Computer-assisted transfer of programmed elutions in reversed-phase high
      performance liquid chromatography.
AB  - Computer-assisted procedures were used to simulate modifications in chromatograms
      caused by the transfer of elution programmes between instruments with
      significantly different dwell volumes. Moreover, for the first time the same
      approach was used to modify the elution programmes to match the chromatograms
      produced in the different instruments. The process may consist of making minor
      modifications to gradient programmes or transforming the original gradient
      programme into a stepwise gradient profile and/or the simultaneous programming of
      flow and solvent composition. The combination of these approaches has been shown
      to have an enormous potential for producing matched chromatograms in instrumental
      systems with dwell volumes that differ by several millilitres. The efficiency and
      robustness of the proposed procedure is demonstrated with a variety of compounds
      (two different mixtures of 10 and 11 analytes), mobile phases (methanol and
      acetonitrile gradients), flow rates (0.5-1.5 mL/min range), temperatures (35-45
      degrees C interval) and gradient profiles (linear, multilinear, curved and
      stepwise).

PMID- 16814797
TI  - Application of gradient programs for the determination of underivatized amino
      acids and small peptides in reversed-phase high-performance liquid chromatography
      with contactless conductivity detection.
AB  - The application of gradient methods in HPLC determinations with capacitively
      coupled contactless conductivity detection was successfully demonstrated for non
      UV-absorbing amino acids as well as for small peptides as analytes. The drift in
      baseline which is caused by the change in the conductivity of the mobile phase
      during the elution could be minimized by careful optimization of the composition
      of the mobile phase. For such conditions the remaining baseline drift could be
      corrected for either by subtraction of a blank chromatogram or by baseline
      normalization using a software package for chromatographic data processing.
      Reverse phase separations were carried out using aqueous eluents containing
      either methanol or acetonitrile and acetic acid or trifluoroacetic acid.
      Detection limits between 1 and 40 microM were achieved for the amino acids and
      the di- and tri-peptides investigated. The reproducibilities for the peak areas
      were typically found to be about 2% and good linearity was obtained for the
      concentration range tested (up to 1000 microM).

PMID- 16814799
TI  - Deformation of gradient shape as a result of preferential adsorption of solvents
      in mixed mobile phases.
AB  - Gradient elution has been studied in typical normal and reversed-phase systems.
      Deformations of gradient profiles have been evidenced as a result of preferential
      adsorption of modifiers of the mobile phase. This phenomenon was pronounced in
      the normal-phase system, for which gradient profiles deviated significantly from
      those programmed. This influenced the retention and shapes of band profiles of
      the eluting solute. Hence, in order to predict gradient propagation correctly the
      adsorption equilibrium of modifiers has been quantified. Moreover, at low
      modifier content, deformations of band profiles of the solute has been registered
      as a result of the competitive adsorption in the system solute-modifier. This
      effect has been predicted by a competitive adsorption model. For the reversed
      phase systems the influence of the modifier adsorption on gradient propagation
      was insignificant for typical mobile phases investigated. Therefore, the work has
      been focused on gradient predictions in the normal-phase system.

PMID- 16814798
TI  - Retention in gas-liquid chromatography with a polyethylene oxide stationary
      phase: molecular simulation and experiment.
AB  - Configurational-bias Monte Carlo simulations in the isobaric-isothermal Gibbs
      ensemble were carried out to investigate the partitioning of normal alkanes,
      primary and secondary alcohols, symmetric alkyl ethers and arenes between a
      helium vapor phase and a polyethylene oxide stationary phase (M(W)=382 g mol(
      1)). The united-atom version of the transferable potentials for phase equilibria
      force field was used to model all solutes, polyethylene oxide and helium. The
      Gibbs free energies of transfer and Kovats retention indices of the solutes were
      calculated directly from the partition constants at two different temperatures,
      353 and 393 K. Chromatographic experiments on a Carbowax 20M retentive phase were
      performed for the same set of solutes and temperatures ranging from 333 to 413 K.
      The predicted retention indices for alcohols, ethers and arenes are overestimated
      by about 120, 70 and 20 retention index units, respectively, pointing to an
      overestimation of the first-order electrostatic interactions in the model system.
      Molecular-level analysis shows that hydrogen-bonding and dipole-dipole
      interactions lead to orientational ordering for the alcohol and ether analytes,
      whereas the weaker dipole-quadrupole interactions for the arene solutes are not
      sufficient to induce orientational ordering. The retention indices of alcohols
      and ethers decrease with increasing temperature because of the large entropic
      cost of hydrogen-bonding and orientational ordering. In contrast, the retention
      indices for arenes increase with increasing temperature because the entropic cost
      of cavity formation is smaller for arenes than for comparable alkanes.

PMID- 16814800
TI  - Controllable size, shape and morphology of molybdic acid self-aggregated with
      rhodamine B to construct functional material.
AB  - Controllable size, shape and morphology of rhodamine B/molybdic acid (RBMA)
      aggregates were prepared from a self-aggregation reaction in a molybdic acid and
      rhodamine B (RhB) coexisting solution. Nanodisks, as well as microcrystal rods
      and polyhexagonal microcrystal rods, have been obtained in conventional bulk
      solutions at different temperatures. Large-sized network microcrystal rods and
      branched fractal aggregates constructed with nanosubunits after the nucleation
      duration of an ice-water-cooled process have also been achieved under the
      evaporation-enhanced conditions on glass substrates. The factors affecting the
      size, shape and morphology of RBMA aggregates including temperature, nucleation
      and growth, and processing conditions are discussed. The results show that
      photofunctional molecules (RhB) modified the surface of the molybdic acid
      particles and influenced their self-aggregation. The temperature and nucleation
      play key roles in the formation of RBMA aggregates. The structures of RBMA
      aggregates were characterized by X-ray diffraction, infrared spectra and
      elemental dispersive spectroscopy. The results indicate that the aggregates show
      the characteristics of RhB-mediated hydrated ammonium molybdenum bronze with the
      metastable hexagonal phase. Visible-light-induced electrons transfer reactions in
      the RBMA aggregates from rhodamine B molecules to MoO3 matrixes were measured by
      UV-vis spectra and X-ray photoelectron spectra, and the fluorescent image was
      observed by laser scanning confocal microscopy.

PMID- 16814801
TI  - In-situ demonstration of mitogen-activated protein kinase Erk 1/2 signalling
      pathway in contagious respiratory tumours of sheep and goats.
AB  - Ovine pulmonary adenocarcinoma (OPA) and enzootic nasal adenocarcinoma (ENA) are
      two contagious neoplastic diseases of secretory epithelial cells in the
      respiratory system of sheep and goats. Jaagsiekte sheep retrovirus (JSRV) is the
      aetiological agent of OPA, and enzootic nasal tumour virus (ENTV) is associated
      with ENA. The genomes of these retroviruses do not contain known oncogenes but
      products of the env gene are important in the generation of transforming stimuli.
      However, the cell signalling pathways activated in vivo are not completely
      understood. This study was based on the use of activation stage antibodies
      specifically detecting proteins of the extracellular signal regulated kinase Erk
      1/2 cell signalling pathway and transcription factors. Tissue sections were
      collected from four natural cases of OPA, four experimentally induced OPA
      tumours, four ENA tumours in sheep, four ENA tumours in goats, two normal sheep
      lungs and two lungs with chronic inflammation. Routine immunohistochemical
      procedures with phosphorylation stage-specific antibodies were carried out.
      Representative proteins of the Erk1/2 pathway (Raf-1, Mek1/2 and p44/42MAPK) were
      activated in natural cases of OPA and ENA in sheep and goats and also in
      experimentally induced OPA. Transcription factors 90Rsk and Elk-1 were activated
      in OPA and ENA tumours. However, c-Myc was activated only in OPA tumours. In
      contagious respiratory neoplasms of sheep and goats the Erk1/2 pathway appears to
      be important for the in-vivo generation of the transforming stimuli.

PMID- 16814802
TI  - The intradermal Leishmanin reaction induces antigen-specific maturation of canine
      dendritic cells with up-regulation of MHCII synthesis and expression.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that reside in
      many tissues, including the skin. This study showed that intradermal injection of
      leishmanin in Leishmania infantum-infected dogs induced the "up-regulation" of
      surface MHCII expression, associated with progressive ultrastrucutural changes
      characteristic of DC maturation, including the formation of multilaminar MHC
      class II-containing compartments and arrays of tubulo-vesicular structures. These
      changes were not observed in control dogs from L. infantum non-endemic areas. The
      results indicated that canine DCs were effector cells in delayed-type
      hypersensitivity, that the leishmanin reaction was specific for a cell-mediated
      reaction to L. infantum in infected dogs, and that canine DCs possessed
      ultrastructural organelles reminiscent of those in activated human DCs.

PMID- 16814803
TI  - An unusual mucinous osteoma with features of an ossifying fibroma in the nasal
      cavity of a horse.
AB  - A 4-month-old Warm-blooded colt presented with facial distorsion and an abnormal
      respiratory noise of 2 weeks' duration. A proliferative mass was found
      endoscopically and by computer tomography. Clinical differential diagnosis
      included cyst formation of the concha, malformation and neoplasia. Euthanasia was
      followed by post-mortem examination, which revealed a well-circumscribed, semi
      solid, jelly like structure, measuring 14.5 x 9.0 x 12.0 cm, in the left
      posterior nasal cavity extending into the left frontal and maxillary sinus.
      Histologically, the mass consisted of trabeculae of woven bone, focal lamellar
      bone and fibroblast proliferation within a moderate fibro-vascular stroma.
      Abundant mucin production was noted within areas of fibroblastic differentiation.
      Some areas contained irregularly shaped spicules of osteoid rimmed by
      osteoblasts, randomly distributed within a moderately vascularized, fibro-osseous
      stroma. On the basis of the histopathological features, a nasal mucinous osteoma
      with focal ossifying fibroma-like structures was diagnosed.

PMID- 16814804
TI  - Natural killer-like T-cell lymphoma in a calf.
AB  - A case of natural killer (NK)-like T-cell lymphoma in a 9-month-old female
      Holstein calf is described. The liver, spleen and lymph nodes were affected with
      lymphoma. The neoplastic cells showed not only epitheliotropism in the biliary
      epithelium and hepatic cords but also preferential homing to follicular centres
      of the lymph nodes. In the cytoplasm, there were eosinophilic granules of various
      sizes, which were positive with phosphotungstic acid haematoxylin and naphthol AS
      D chloroacetate esterase. Erythrophagia by lymphoma cells was rarely detected.
      Immunohistochemically, the neoplastic cells expressed surface CD3, surface CD5
      and CD57, and perforin expression was present in the cytoplasmic granules. The
      lymphoma described resembled feline NK-like T-cell lymphoma in epitheliotropism
      in the liver and phagocytic activity but differed in respect of follicular
      involvement and marked variation in granule size.

PMID- 16814805
TI  - Microsporidian infections in Lymantria dispar larvae: interactions and effects of
      multiple species infections on pathogen horizontal transmission.
AB  - The interactions in multiple species infections and effects on the horizontal
      transmission of three microsporidian species, Vairimorpha disparis, Nosema
      lymantriae and Endoreticulatus schubergi, infecting Lymantria dispar were
      evaluated in the laboratory. Simultaneous and sequential inoculations of host
      larvae were performed and the resulting infections were evaluated. Test larvae
      were exposed to the inoculated larvae to measure horizontal transmission. Dual
      species infections demonstrated interspecific competition between Nosema and
      Vairimorpha in the host larvae, but no observable competition occurred between
      Endoreticulatus and either of the other microsporidian species. Timing of
      inoculation was an important factor determining the outcome of competition
      between Nosema and Vairimorpha. The species inoculated first showed a higher rate
      of successful establishment; a time lag of 7 days between inoculations allowed
      the first species to essentially exclude the second. The microsporidia differed
      in efficiency of horizontal transmission. Nosema and Endoreticulatus were
      transmitted at very high rates, close to 100%. Horizontal transmission of
      Vairimorpha was less efficient, ranging from 25% to a maximum of 75%. The
      patterns of infection observed in inoculated larvae were reflected in the test
      larvae that acquired infections in the horizontal transmission experiments.
      Competition with Vairimorpha suppressed horizontal transmission of Nosema after
      simultaneous and sequential inoculation. In simultaneous inoculation experiments
      Endoreticulatus had no effect on transmission of Nosema and Vairimorpha.

PMID- 16814806
TI  - Physical and functional interactions between the prostate suppressor homeoprotein
      NKX3.1 and serum response factor.
AB  - The NKX3.1 transcription factor is an NK family homeodomain protein and a tumor
      suppressor gene that is haploinsufficient and down-regulated in the early phases
      of prostate cancer. Like its cardiac homolog, NKX2.5, NKX3.1 acts synergistically
      with serum response factor (SRF) to activate expression from the smooth muscle
      gamma-actin (SMGA) gene promoter. Using NMR spectroscopy, three conserved motifs
      in a construct containing the N-terminal region and homeodomain of NKX3.1 were
      observed to interact with the MADS box domain of SRF. These motifs interacted
      both in the absence of DNA and when both proteins were bound to a SMGA promoter
      DNA sequence. No significant interaction was seen between the homeodomain and SRF
      MADS box. One of the SRF-interacting regions was the tinman (TN) or engrailed
      homology-1 motif (EH-1), residues 29-35 (FLIQDIL), which for other NK proteins is
      the site of interaction with the repressor protein Groucho. A second hydrophobic
      interacting region was designated the SRF-interacting (SI) motif and included
      residues 99-105 (LGSYLLD). A third interacting motif was the acidic region
      adjacent to the SI motif including residues 88-96 (ETLAETEPE). The acidic domain
      (AD) motif signals also showed strengthening upon the NKX3.1 homeodomain binding
      to DNA in the absence of SRF, consistent with the acidic region weakly
      interacting with the homeodomain in the unbound state. The importance of these
      linear motifs in the transcriptional interaction of NKX3.1 and SRF was
      demonstrated by targeted mutagenesis of an NKX3.1 expression vector in a SMGA
      reporter assay. The results implicate the NKX3.1 N-terminal region in regulation
      of transcriptional activity of this tumor suppressor.

PMID- 16814807
TI  - Cognitive decline correlates with neuropathological stage in Parkinson's disease.
AB  - Recently, the relationship between cognitive status and the neuropathological
      stages of a newly proposed staging procedure for Parkinson's disease (PD) was
      assessed in a cohort of 88 individuals. None of the patients had received the
      clinical diagnosis of dementia with Lewy bodies. The topographic distribution
      pattern of the cerebral Lewy body pathology was evaluated semiquantitatively in
      alpha-synuclein immunoreactions. MMSE scores from the last neurological
      examination prior to death were used to determine cognitive status and the degree
      of cognitive decline. Four subgroups of Mini-Mental State Examination (MMSE)
      scores ranging from nonsignificantly impaired to severely impaired cognition were
      analyzed statistically with nonparametric tests. Each of the 88 cases could be
      assigned to one of the PD stages 3-6, and MMSE scores correlated significantly
      with the aforementioned stages. Since the median MMSE scores decreased from
      stages 3-6, it is probable that the risk of developing dementia in PD becomes
      greater as the disease process in the brain progresses.

PMID- 16814808
TI  - Effects of the dopamine agonist pramipexole on depression, anhedonia and motor
      functioning in Parkinson's disease.
AB  - Depression affects approximately 45% of all patients with Parkinson's disease,
      reduces quality of live independent of motor symptoms and seems to be underrated
      and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at
      cortico-frontal dopamine receptors and neurotrophic effects which seem to relate
      to its antidepressant and anti-anhedonic properties in Parkinson's disease and
      bipolar depression found in controlled studies. In the present study, effects of
      pramipexole were investigated under routine clinical conditions. Anhedonia was
      measured in patients with Parkinson's disease (n=657) using the self-rated Snaith
      Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated
      Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all
      patients and in 79.7% of the depressed patients with Parkinson's disease. Mild
      depression was present in 47%, moderate to severe depression in 22% of the
      patients. At the end of the study period of 9 weeks on an average, the mean
      dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of
      depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well
      as motor deficits were significantly reduced during treatment with pramipexole.
      Drop-outs due to adverse events occurred in 3.5%. Future studies should
      investigate specificity of anti-anhedonic and antidepressive properties of
      pramipexole.

PMID- 16814809
TI  - The comparison of immobility time in experimental rat swimming models.
AB  - Rat swimming models have been used in studies about stress and depression.
      However, there is no consensus about interpreting immobility (helplessness or
      adaptation) in the literature. In the present study, immobility time, glucose and
      glycogen mobilization, corticosterone and the effect of desipramine and diazepam
      were investigated in two different models: swimming stress and the forced
      swimming test. Immobility time was lower in swimming stress than in the forced
      swimming test. Both swimming models increased corticosterone levels in comparison
      with control animal levels. Moreover, swimming stress induced higher
      corticosterone levels than the forced swimming test did [F(2,14)=59.52; p<0.001].
      Liver glycogen content values differed from one another (swimming stress<forced
      swimming test<control), [F(2,17)=32.08; p<0.001]. The glycogen content values in
      the gastrocnemius [F(2,16)=11.35; p=0.026] and soleus [F(2,16)=8.68; p=0.006]
      muscles were lower during swimming stress in comparison with the forced swimming
      test and control. The immobility time was recorded and measured in another group
      treated with desipramine and diazepam in two protocols: a single session of
      forced swimming test or swimming stress and two sessions (pre- and retest) of
      forced swimming model or swimming stress. Desipramine decreased the immobility
      time in the forced swimming test in both the single [F(2,25)=20.63; p<0.0001] and
      retest [F(2,37)=7.28; p=0.002] swimming session, without changes in the swimming
      stress model. Diazepam increased the immobility time in the swimming stress but
      not in the forced swimming test during the single [F(2,26)=11.24; p=0.0003] and
      retest sessions [F(2,38)=4.17; p=0.02]. It was concluded that swimming stress and
      the forced swimming test induced different behavior, hormonal and metabolic
      responses and represented different situations to the animal.

PMID- 16814810
TI  - Exposure of inner-shelf reefs to nutrient enriched runoff entering the Great
      Barrier Reef Lagoon: post-European changes and the design of water quality
      targets.
AB  - We used historical flood plume extent data (modelled) to quantify the typical
      spatial extent of the summer runoff-seawater mixing zone of the Great Barrier
      Reef (GBR) lagoon. Spatially explicit analysis of the variability of in situ
      chlorophyll a concentrations (observed) across the runoff-seawater mixing zone,
      then allowed us to explore regional differences in the nutrient enrichment impact
      of runoff events from the various river systems that drain the GBR catchment. We
      demonstrate the existence of a discernable north-south gradient along the length
      of the GBR, such that for equivalent runoff:seawater dilutions ratios, lower
      levels of nutrient enrichment (as indicated by chlorophyll alpha observations)
      result from the river systems that drain the relatively undisturbed northern
      areas of the GBR catchment, compared to more human-impacted central and south
      areas. We identify a strong correlation between this north-south enrichment
      gradient and the flood concentration of dissolved inorganic nitrogen (DIN)
      entrained by the various river systems. By substituting the nutrient enrichment
      characteristics of the human-impacted river discharges with those of the
      undisturbed northern rivers, we provide a means to compare the short-term
      enriching 'footprint' for existing runoff intrusions with those that are likely
      to have occurred under pre-European catchment conditions. We demonstrate that
      under pre-European conditions, the nutrient enriching impact from river runoff
      was likely to have been largely constrained within 1-2 km of the coast, whereas
      existing conditions support the impact of reefs some 20-30 km off the coast. By
      using the developed spatial relations, we show that for the heavily human
      impacted river systems, reductions in the end-of-river concentrations of DIN in
      the order 50-80% are needed in order to restore parity with pre-European
      conditions. We discuss these results in regard to developing end-of-catchment
      water quality targets for the region.

PMID- 16814811
TI  - Paired box genes, PAX-2 and PAX-8, are not frequently mutated in Wilms tumor.
AB  - To determine whether PAX-2 and PAX-8 are involved in Wilms tumor (WT)
      pathogenesis, we sought mutations in these two genes in 99 Wilms tumors of
      favorable histology. We screened the entire protein coding sequences as well as
      the intronic regions adjacent to exons, using denaturing HPLC followed by
      sequencing of samples displaying abnormal chromatograms. In PAX-2, a silent
      polymorphism was found within exon 2 and exon 8 in 1% and 21% of cases,
      respectively. Three apparently silent polymorphisms were also found in PAX-8, two
      in exon 5 (2 of 99 cases or 2%) and one in exon 6 (22 of 99 cases or 22%), all of
      which were located 3' to the exons. In conclusion, no evidence for disease
      causing mutation was found using this technique, and so the direct involvement of
      either of these two genes in WT is unlikely.

PMID- 16814812
TI  - Does loss of heterozygosity in critical genome regions predict a local relapse in
      patients after laryngectomy?
AB  - BACKGROUND: Patients, who had an upper aerodigestive tract malignancy, have a
      high incidence of succeeding tumor development. This has been attributed to the
      role of "field cancerization" in carcinogenesis. The aim of this study was
      analysis of loss of heterozygosity (LOH) in the regions frequently lost during
      the course of head and neck squamous cell carcinomas (HNSCC), especially at early
      stages, which could answer the clinicians' question, if LOH analysis has any
      "predictive" value in relation to tumor occurrence. MATERIAL AND METHODS: Sixty
      five larynx cancer patients were examined for loss of heterozygosity on 3p, 7q,
      8p, 9p and 18q chromosomal arms with the use of 12 microsatellite markers. The
      material from a single patient consisted of blood, tumor, safe margin and one or
      two clinically unchanged mucosal samples. During follow up, the material from
      brush specimens (14 patients) as well as laryngeal swabs (4 patients) was also
      examined. RESULTS: The highest frequency of LOH was detected for marker D3S1234
      in tumor tissues (29%). Analysis of margin samples (b) revealed low LOH
      frequencies (2-5%) and complete retention of heterozygosity for markers: D3S1234,
      D7S486, D8S261, D8S264, D9S171 and D18S46. Similarly, for normal appearing mucosa
      from upper part of larynx (c) frequencies of LOH were low (2-6%), with the
      complete retention of heterozygosity for markers: D3S1284, D3S1304, D3S1234,
      D8S264 and D9S1870. We did not detect any LOH in the material of normal appearing
      mucosa from tracheostoma region (d). During follow up, LOH was detected for eight
      markers, with the highest incidence for markers D18S46 (six cases), D7S486 (four
      cases) and D3S1300 (three cases). CONCLUSIONS: The data, obtained during this
      investigation, did not reveal the predictive value of LOH with respect to local
      relapse occurrence in laryngeal cancer patients. However, time of follow up did
      not reach 5 years, so that further clinical monitoring should be conducted.

PMID- 16814813
TI  - Chromosomal aberrations and SCEs as biomarkers of cancer risk.
AB  - Previous studies have suggested that the frequency of chromosomal aberrations
      (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We
      have further examined this relationship in European cohorts comprising altogether
      almost 22,000 subjects, in the framework of a European collaborative project
      (CancerRiskBiomarkers). The present paper gives an overview of some of the
      results of the project, especially as regards CAs and SCEs. The results confirm
      that a high level of CAs is associated with an increased risk of cancer and
      indicate that this association does not depend on the time between CA analysis
      and cancer detection, i.e., is obviously not explained by undetected cancer. The
      present evidence indicates that both chromatid-type and chromosome-type CAs
      predict cancer, even though some data suggest that chromosome-type CAs may have a
      more pronounced predictive value than chromatid-type CAs. CA frequency appears to
      predict cancers at various sites, although there seems to be a particular
      association with gastrointestinal cancers. SCE frequency does not appear to have
      cancer predictive value, at least partly due to uncontrollable technical
      variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA
      repair, and folate metabolism affect the level of CAs and might collectively
      contribute to the cancer predictivity of CAs. Other factors that may influence
      the association between CAs and cancer include, e.g., exposure to genotoxic
      carcinogens and internal generation of genotoxic species. Although the
      association between CA level and cancer is seen at the group level, an
      association probably also exists for the individual, although it is not known if
      an individual approach could be feasible. However, group level evidence should be
      enough to support the use of CA analysis as a tool in screening programs and
      prevention policies in occupational and environmental health.

PMID- 16814814
TI  - Genome-wide differential gene expression in children exposed to air pollution in
      the Czech Republic.
AB  - The Teplice area in the Czech Republic is a mining district where elevated levels
      of air pollution including airborne carcinogens, have been demonstrated,
      especially during winter time. This environmental exposure can impact human
      health; in particular children may be more vulnerable. To study the impact of air
      pollution in children at the transcriptional level, peripheral blood cells were
      subjected to whole genome response analysis, in order to identify significantly
      modulated biological pathways and processes as a result of exposure. Using genome
      wide oligonucleotide microarrays, we investigated differential gene expression in
      children from the Teplice area (n=23) and compared them with children from the
      rural control area of Prachatice (n=24). In an additional approach, individual
      gene expressions were correlated with individual peripheral blood lymphocyte
      micronuclei frequencies, in order to evaluate the linkage of individual gene
      expressions with an established biomarker of effect that is representative for
      increased genotoxic risk. Children from the Teplice area showed a significantly
      higher average micronuclei frequency than Prachatice children (p=0.023). For
      considerable numbers of genes, the expression differed significantly between the
      children from the two areas. Amongst these genes, considerable numbers of genes
      were observed to correlate significantly with the frequencies of micronuclei. The
      main biological process that appeared significantly affected overall was
      nucleosome assembly. This suggests an effect of air pollution on the primary
      structural unit of the condensed DNA. In addition, several other pathways were
      modulated. Based on the results of this study, we suggest that transcriptomic
      analysis represents a promising biomarker for environmental carcinogenesis.

PMID- 16814816
TI  - Gz proteins are functionally coupled to dopamine D2-like receptors in vivo.
AB  - The receptors that couple to the G protein Gz in vivo are still relatively
      unknown. In this study, we investigated the effects of various dopamine receptor
      agonists in a mouse deficient in the alpha subunit of Gz. The dopamine D1-like
      receptor agonist SKF38393 stimulated comparable locomotor activity in both
      wildtype mice and mice lacking Galphaz. In contrast, the dopamine D2-like
      receptor agonist quinpirole suppressed locomotor activity in both groups of mice,
      but this suppression was significantly smaller in Galphaz knockout mice.
      Consistent with these behavioural observations, quinpirole inhibition of dopamine
      release in the forebrain nucleus accumbens evoked by electrical stimulation of
      dopamine axons was significantly attenuated in mice lacking Galphaz. In addition,
      hypothermia and adrenocorticotropic hormone release resulting from activation of
      dopamine D2-like receptors were also significantly reduced in Galphaz knockout
      mice. However, adrenocorticotropic hormone secretion induced by corticotrophin
      releasing hormone and the serotonin 1A receptor agonist 8-hydroxy-dipropylamino
      tetralin were similar between wildtype and Galphaz knockout mice. Western blot
      analysis showed that the expression levels of Galphai, Galphao, Galphas, Galphaq
      and Gbeta were the same in the brains of mice of both genotypes. Overall, our
      data suggest that Gz proteins are functionally coupled to dopamine D2-like
      receptors in vivo.

PMID- 16814815
TI  - Intrathecal clonidine suppresses zymosan-induced peripheral leukocyte migration
      in a mouse air pouch model via activation of spinal muscarinic type 2 receptors
      and sympathoadrenal medullary activity.
AB  - These studies were performed to examine the potential anti-inflammatory effect of
      intrathecal (IT) clonidine (an alpha2-adrenoceptor agonist) on zymosan-induced
      leukocyte migration in a mouse air pouch model. IT clonidine dose-dependently
      suppressed zymosan-induced leukocyte migration and this effect was blocked by IT
      idazoxan (an alpha2-adrenoceptor antagonist) pretreatment. Since a number of
      studies have previously shown that spinal alpha2-adrenoceptors are functionally
      associated with spinal cholinergic activity, we next examined whether spinal
      acetylcholine (ACh) receptors were also involved in mediating this anti
      inflammatory effect of IT clonidine. IT pretreatment with atropine (a muscarinic
      receptor antagonist), but not hexamethonium (a nicotinic receptor antagonist)
      completely blocked the anti-migratory effect of IT clonidine. Subsequent
      experiments showed that IT pretreatment with methoctramine (a muscarinic M2
      antagonist), but not pirenzepine (an M1 antagonist) or 4-DAMP (an M3 antagonist),
      suppressed clonidine's anti-inflammatory effect. Finally, we studied the
      potential roles of the sympathetic nervous system and the hypothalamo-pituitary
      adrenal axis in clonidine's anti-inflammatory effect. Adrenalectomy or systemic
      injection of propranolol (a beta-adrenoceptor antagonist) blocked clonidine's
      effect. However, pretreatment with RU486 (a corticosteroid antagonist) or
      peripheral sympathetic denervation using 6-hydroxydopamine had no effect.
      Furthermore, IT clonidine increased Fos expression in zymosan treated mice
      exclusively in T7-T11 sympathetic preganglionic neurons (which mainly project to
      the adrenal medulla), but not those of the T1-T6 or T12-L2 spinal segments.
      Moreover, IT methoctramine significantly reduced this increase in Fos expression.
      Collectively, these findings suggest that IT clonidine suppresses peripheral
      leukocyte migration via a sympathoadrenal medullary pathway, and that this
      suppressive effect is mediated by spinal M2 receptors.

PMID- 16814817
TI  - Discriminative stimulus properties of the selective and highly potent alpha2
      adrenoceptor agonist, S18616, in rats: mediation by the alpha2A subtype, and
      blockade by the atypical antidepressants, mirtazapine and mianserin.
AB  - The novel spiroimidazoline, S18616, a potent and efficacious agonist at alpha2
      adrenoceptors (ARs), shows>100-fold selectivity versus alpha1-ARs, imidazoline
      receptors and all other sites examined. Herein, we characterized its
      discriminative stimulus (DS) properties in rats trained to recognise S18616 (0.01
      mg/kg, s.c.) from saline. S18616 dose-dependently (0.0063-0.01) and "fully"
      (>or=80% "S18616" lever selection) substituted for itself. Full substitution was
      also acquired for the agonist, UK14,304 (0.04-0.16), while the partial agonist,
      clonidine (0.01-0.08), yielded sub-maximal substitution (67%). Guanfacine (0.16
      1.25) and guanabenz (0.00063-0.04), preferential agonists at alpha2A-ARs,
      revealed full substitution for S18616. In contrast, the alpha1-AR agonists,
      cirazoline and ST587 (both 0.04-0.63), did not substitute. The alpha2-AR
      antagonists, RX821,002, atipamezole (both 0.0025-0.04) and idazoxan (0.04-0.63)
      blocked the S18616 DS, whereas the alpha1-AR antagonists, prazosin (0.16-0.63)
      and WB4101 (0.04-0.63), were inactive. Prazosin is also a preferential antagonist
      at alpha2B/2C- versus alpha2A-ARs and a further preferential alpha2B/2C-AR
      antagonist, BRL41,992 (0.63-2.5), was likewise ineffective. In contrast, the
      alpha2A-AR antagonist, BRL44,408 (0.04-0.16), dose-dependently abolished the
      S18616 DS. Finally, the "atypical" antidepressants, mirtazapine (0.16-10.0) and
      mianserin (0.63-10.0), which behave as antagonists at alpha2A-ARs, dose
      dependently blocked the S18616 DS. In conclusion, S18616 elicits a robust DS in
      rats that principally reflects engagement of alpha2A-ARs. This novel procedure
      should prove useful in the characterisation of psychoactive drugs which interact
      with alpha2-ARs.

PMID- 16814818
TI  - Neural responses to dynamic expressions of fear in schizophrenia.
AB  - Abnormalities in social functioning are a significant feature of schizophrenia.
      One critical aspect of these abnormalities is the difficulty these individuals
      have with the recognition of facial emotions, particularly negative expressions
      such as fear. The present work focuses on fear perception and its relationship to
      the paranoid symptoms of schizophrenia, specifically, how underlying limbic
      system structures (i.e. the amygdala) react when probed with dynamic fearful
      facial expressions. Seven paranoid and eight non-paranoid subjects (all males)
      with a diagnosis of schizophrenia took part in functional magnetic resonance
      imaging study (1.5T) examining neural responses to emerging fearful expressions
      contrasted with dissipating fearful expressions. Subjects viewed emerging and
      dissipating expressions while completing a gender discrimination task. Their
      brain activation was compared to that of 10 healthy male subjects. Increased
      hippocampal activation was seen in the non-paranoid group, while abnormalities in
      the bilateral amygdalae were observed only in the paranoid individuals. These
      patterns may represent trait-related hippocampal dysfunction, coupled with state
      (specifically paranoia) related amygdala abnormalities. The findings are
      discussed in light of models of paranoia in schizophrenia.

PMID- 16814820
TI  - Pongamone A-E, five flavonoids from the stems of a mangrove plant, Pongamia
      pinnata.
AB  - Chemical investigation of stems of the mangrove plant, Pongamia pinnata, resulted
      in isolation and characterization of five structurally unusual flavonoids
      pongamones A-E, along with 16 known flavonoid metabolites. Their structures were
      determined on the basis of spectroscopic analyses and by comparison of their
      spectroscopic data with those of related compounds reported in the literature.
      Pongamones A-E were assayed against DHBV RCs DNAP and HIV-1 RT in vitro. A
      possible biogenetic pathway of the isolated compounds is also proposed.

PMID- 16814819
TI  - Heightened false memory: a long-term sequela of severe closed head injury.
AB  - Declarative memory impairment is a common long-term sequela of severe closed head
      injury (CHI). Although veridical memory performance following severe CHI has
      received attention in the literature, little is known about false memory
      production in this population. Within the present study, both long-term survivors
      of severe CHI and matched control participants studied and were tested on six 12
      items word lists from the Deese Roediger McDermott (DRM) paradigm. Word lists
      from the DRM are composed of words that are strongly semantically associated to a
      non-presented word (i.e., the critical lure). Prior studies have shown that
      healthy young adults show a high level of false recall and recognition memory for
      the critical lures, and it was hypothesized individuals with severe CHI would
      show heightened susceptibility to false memory compared to control participants
      due to difficulty with monitoring of memory. It was further hypothesized that
      severe CHI participants would show high confidence in their false memories.
      Consistent with hypotheses, results indicated that although severe CHI
      participants remembered fewer actual list items, they made more semantically
      related intrusion errors (recall) and false-positive responses (recognition) than
      the control participants. Severe CHI participants also showed greater confidence
      in their false memories than did control participants. The results are
      interpreted in the context of theoretical accounts of false memory, and possible
      structural and functional brain changes that might account for the Severe CHI
      group's memory performance are discussed.

PMID- 16814821
TI  - Clinical and epidemiological characteristics of yellow fever in Brazil: analysis
      of reported cases 1998-2002.
AB  - Yellow fever (YF), an arboviral infection of major public health importance in
      Brazil, is associated with high mortality and high epidemic potential. We
      analysed confirmed YF cases from the National Surveillance System from 1998-2002
      and assessed risk factors for death among hospitalised patients. Variables
      assessed included age, gender, clinical signs and laboratory findings. A logistic
      regression model was used to identify independent predictors of death among
      hospitalised patients. From 1998-2002, among 2117 suspected YF cases reported to
      Brazil's Ministry of Health, 251 (11.9%) had confirmed YF, of whom 217 (86.5%)
      were hospitalised and the case fatality rate was 44.2%. Factors associated with
      higher mortality in univariate analysis included male gender (relative risk (RR)
      1.96, 95% CI 1.17-2.28), age >40 years (RR 2.61, 95% CI 1.25-5.45), jaundice (RR
      2.66, 95% CI 2.12-3.35), serum aspartate aminotransferase (AST) >1200 IU/l (RR
      1.84, 95% CI 1.23-2.74), alanine aminotransferase >1500 IU/l (RR 2.09, 95% CI
      1.38-3.17), total bilirubin >7.0mg/dl (RR 2.33, 95% CI 1.44-3.78), direct
      bilirubin >5.0mg/dl (RR 2.29, 95% CI 1.33-3.94) and blood urea nitrogen >100mg/dl
      (RR 5.77, 95% CI 1.43-23.22). In multivariate analysis, elevated AST and jaundice
      remained independently associated with higher mortality. These findings suggest
      that selected clinical and laboratory indicators may help clinicians recognise
      potentially fatal cases of YF.

PMID- 16814822
TI  - High rates of HIV in surgical patients in Soweto, South Africa: impact on
      resource utilisation and recommendations for HIV testing.
AB  - Interactions between HIV and surgical diseases are relatively poorly described in
      high HIV prevalence settings. We report HIV prevalence and its associations in a
      prospective study of adults admitted to surgical units in Soweto, South Africa.
      Voluntary counselling and testing (VCT) for HIV was offered to surgical
      inpatients. Research nurses interviewed participants at enrolment and doctors
      reviewed records after discharge. In HIV-infected participants, CD4 counts and
      viral loads were ascertained. Of 1000 participants, 537 consented to VCT, of whom
      176 (32.8%, 95% CI 28.8-36.9%) tested HIV positive. A history of tuberculosis
      (adjusted odds ratio (AOR) 3.0, 95% CI 1.5-6.2) or sexually transmitted infection
      (AOR 2.7, 95% CI 1.8-4.2) was associated with HIV infection. Diagnoses of
      cutaneous abscesses (OR 3.4, 95% CI 1.4-8.1) and anorectal sepsis (OR 3.1, 95% CI
      1.1-9.0) were associated with HIV and indicated advanced disease. There were no
      differences in rates of operative procedures, wound sepsis, investigations or
      length of stay by HIV status. Hospital-acquired pneumonia was more common in HIV
      infected participants (P=0.028). In conclusion, in this high HIV prevalence
      setting, resource utilisation is similar between HIV-infected and uninfected
      patients in surgical wards where high rates of HIV in young adults support
      routine HIV testing. WHO clinical staging of HIV should include anal sepsis as an
      indicator of advanced HIV disease.

PMID- 16814823
TI  - Gender differences in gastrointestinal disturbances and plasma concentrations of
      tafenoquine in healthy volunteers after tafenoquine administration for post
      exposure vivax malaria prophylaxis.
AB  - In an open-label sequential cohort study, we compared gastrointestinal (GI)
      disturbances and plasma tafenoquine concentrations after administration of single
      dose (400mg daily x 3 days; n=76 males, 11 females) and split-dose (200 mg twice
      daily x 3 days; n=73 males, 13 females) tafenoquine regimens in healthy
      Australian Defence Force volunteers for post-exposure malaria prophylaxis. The
      female and male volunteers had comparable demographic characteristics (age,
      weight, height) in the single- and split-dose treatment groups. GI disturbances
      were generally mild and self-limiting for both groups. The frequency of nausea
      and abdominal distress was over two-fold higher in females than in males for both
      treatment groups. Reporting of GI disturbances in the single-dose group differed
      significantly between males and females, but this gender difference was not seen
      for the split-dose group. In those volunteers who experienced GI disturbances,
      the mean plasma tafenoquine concentrations 12 h after the last dose of
      tafenoquine were approximately 1.3-fold higher in females than in males (means+/
      SD: 737+/-118 ng/ml vs. 581+/-113 ng/ml). These preliminary findings suggest that
      further studies are required in a larger number of females to determine whether
      there is a need to reduce the dose of tafenoquine to minimise GI disturbances in
      females.

PMID- 16814824
TI  - A simple approach to optimal control of invasive species.
AB  - The problem of invasive species and their control is one of the most pressing
      applied issues in ecology today. We developed simple approaches based on linear
      programming for determining the optimal removal strategies of different stage or
      age classes for control of invasive species that are still in a density
      independent phase of growth. We illustrate the application of this method to the
      specific example of invasive Spartina alterniflora in Willapa Bay, WA. For all
      such systems, linear programming shows in general that the optimal strategy in
      any time step is to prioritize removal of a single age or stage class. The
      optimal strategy adjusts which class is the focus of control through time and can
      be much more cost effective than prioritizing removal of the same stage class
      each year.

PMID- 16814825
TI  - Ultrasonic, chemical stability and preparation of self-assembled fullerene[C60]
      gold nanoparticle films.
AB  - C(60)-functionalized gold nanoparticle films were self-assembled on the reactive
      surface of glass slides functionalized with 3-aminopropyltrimethoxysilane. The
      functionalized glass slides were alternately soaked in the solutions containing
      unmodified C(60) and 4-aminothiophenoxide/hexane thiolate-protected gold
      nanoparticles. Organic reaction (amination) facilitated the layer-by-layer
      multilayer film assembly. C(60)-functionalized gold nanoparticle films have grown
      up to several layers (upto 5 layers were examined) depending on the immersion
      time. The assembled nanoparticle films were characterized using UV-vis
      spectroscopy. The chemical stability of C(60)-gold nanoparticle films was studied
      by monitoring the changes in absorbance after the immersion of the films in
      acidic solutions. The ultrasonic stability of these nanoparticle films was
      studied by exposing them to ultrasonic irradiated surrounding, which results in
      the aggregation of nanoparticles on solid surfaces.

PMID- 16814826
TI  - Piezoelectric transducer design via multiobjective optimization.
AB  - The design of piezoelectric transducers is usually based on single-objective
      optimization only. In most practical applications of piezoelectric transducers,
      however, there exist multiple design objectives that often are contradictory to
      each other by their very nature. It is impossible to find a solution at which
      each objective function gets its optimal value simultaneously. Our design
      approach is to first find a set of Pareto-optimal solutions, which can be
      considered to be best compromises among multiple design objectives. Among these
      Pareto-optimal solutions, the designer can then select the one solution which he
      considers to be the best one. In this paper we investigate the optimal design of
      a Langevin transducer. The design problem is formulated mathematically as a
      constrained multiobjective optimization problem. The maximum vibration amplitude
      and the minimum electrical input power are considered as optimization objectives.
      Design variables involve continuous variables (dimensions of the transducer) and
      discrete variables (the number of piezoelectric rings and material types). In
      order to formulate the optimization problem, the behavior of piezoelectric
      transducers is modeled using the transfer matrix method based on analytical
      models. Multiobjective evolutionary algorithms are applied in the optimization
      process and a set of Pareto-optimal designs is calculated. The optimized results
      are analyzed and the preferred design is determined.

PMID- 16814827
TI  - Food drying process by power ultrasound.
AB  - Drying processes, which have a great significance in the food industry, are
      frequently based on the use of thermal energy. Nevertheless, such methods may
      produce structural changes in the products. Consequently, a great emphasis is
      presently given to novel treatments where the quality will be preserved. Such is
      the case of the application of high-power ultrasound which represents an emergent
      and promising technology. During the last few years, we have been involved in the
      development of an ultrasonic dehydration process, based on the application of the
      ultrasonic vibration in direct contact with the product. Such a process has been
      the object of a detailed study at laboratory stage on the influence of the
      different parameters involved. This paper deals with the development and testing
      of a prototype system for the application and evaluation of the process at a pre
      industrial stage. Such prototype is based on a high-power rectangular plate
      transducer, working at a frequency of 20 kHz, with a power capacity of about 100
      W. In order to study mechanical and thermal effects, the system is provided with
      a series of sensors which permit monitoring the parameters of the process.
      Specific software has also been developed to facilitate data collection and
      analysis. The system has been tested with vegetable samples.

PMID- 16814828
TI  - Generation and detection of incoherent phonons in picosecond ultrasonics.
AB  - In picosecond ultrasonics experiments the absorption of a femtosecond laser pulse
      in a thin metallic transducer is used to generate very short acoustic pulses.
      These pulses are made of coherent longitudinal waves with a frequency spectrum
      that can reach 100-200 GHz. The laser pulse absorption gives rise to a heating of
      the film of a few Kelvin within a typical time of 1 ps. Later on, the heat goes
      in the substrate through an interface thermal resistance and is diffused by
      thermal conduction. At very low temperature and in pure crystals the thermal
      phonons emitted by the heated metallic film can propagate ballistically over
      large distances and produce a so-called heat pulse. We report on the experimental
      evidence of the coexistence of the coherent acoustic pulse and the incoherent
      heat pulse generated and detected by laser ultrasonics.

PMID- 16814829
TI  - Preparation of a water-soluble fullerene [C70] under ultrasonic irradiation.
AB  - A water-soluble fullerene [C(70)] is prepared with fullerene [C(70)] and a
      mixture of concd. sulfuric acid (H(2)SO(4)) and concd. nitric acid (HNO(3)) at
      the ratio (v/v) of 3:1 under ultrasonic irradiation at 25-43 degrees C. The MALDI
      TOF-MS spectra confirmed that the product of a water-soluble fullerene compound
      was C(70).

PMID- 16814830
TI  - Estimation of clamping force in high-tension bolts through ultrasonic velocity
      measurement.
AB  - The estimation of clamping force has been regarded as the main issue in the
      maintenance of high-tension bolts. This paper proposes a method which uses the
      dependency of ultrasonic velocity on stress based on the nonlinear elastic
      effect. The variation of ultrasonic velocity in the range of actual stress acting
      in the bolt is very small so that the precise measurement of ultrasonic velocity
      is needed. In this paper, we adopt a method to measure ultrasonic velocity, where
      the TOF (time of flight) of a tone-burst ultrasonic wave is precisely measured by
      using the phase detection technique. In order to verify the usefulness of the
      proposed method, two kinds of experiments are carried out. The first one measures
      ultrasonic velocity when the bolt is stressed by the tension tester, and from
      this, the exact axial force acting in the bolt can be determined. The results
      show good agreement with the expected linear relationship between ultrasonic
      velocity and axial stress. The second experiment measures ultrasonic velocity
      when the bolt is stressed by the torque wrench. The results show that ultrasonic
      velocity decreased as the torque increased, which is identical to the
      theoretically expected tendency. From these results, it can be said that the
      proposed method is adequate in evaluating clamping force in high-tension bolts.

PMID- 16814831
TI  - Simulation of leaky Rayleigh wave at air-solid cylindrical interfaces by finite
      element method.
AB  - The finite element method is used to simulate the laser-excited leaky Rayleigh
      wave at air-solid cylindrical interfaces. A whole arithmetic of fluid-solid
      interaction is presented, which includes a coupling matrix that describing the
      process of the interaction between fluid and solid, the Arbitrary Lagrangian
      Eulerian (ALE) formulation for treating the variation of fluid domain, which
      results from the Rayleigh wave propagating on the cylindrical interface, etc.
      Typical calculation is executed and the results show that the polarity of leaky
      Rayleigh waveform gradually changes as it propagates on the air-solid cylindrical
      interface.

PMID- 16814832
TI  - Theory and simulation of wave phase conjugation.
AB  - This paper briefly presents the general analytical solution for the resonant
      modes in 1D active magneto acoustic phase conjugators in contact with passive
      media of arbitrary impedance. The first non-resonant but amplified modes are also
      derived. All results are successfully compared with direct numerical simulations.

PMID- 16814833
TI  - Harmonic and subharmonic acoustic wave generation in finite structures.
AB  - The generation of harmonic and subharmonic vibrations is considered in a finite
      monodimensional structure, as it is produced by the nonlinear acoustic
      characteristics of the medium. The equation of motion is considered, where a
      general function of the displacement and its derivatives acts as the forcing term
      for (sub)harmonic generation and a series of 'selection rules' is found,
      depending on the sample constrains. The localization of the nonlinear term is
      also considered that mimics the presence of defects or cracks in the structure,
      together with the spatial distribution of subharmonic modes. Experimental
      evidence is given relative to the power law dependence of the harmonic modes vs.
      the fundamental mode displacement amplitude, and subharmonic mode distribution
      with hysteretic effects is also reported in a cylindrical sample of piezoelectric
      material.

PMID- 16814834
TI  - Two-dimensional analysis of the effect of an electrode layer on surface acoustic
      waves in a finite anisotropic plate.
AB  - The effect of a metal layer over an elastic substrate on surface acoustic wave
      propagating in the structure can be evaluated precisely for semi-infinite solids
      and infinite plates, but there is no accurate analytical solution if the finite
      size of the plate has to be considered. By expanding displacements with
      eigensolutions of surface acoustic waves in a semi-inifite solid, a set of two
      dimensional equations similar to the Mindlin plate theory are obtained. Then for
      a thin electrode layer, the effect is considered through the approximation of
      displacements in the metal layer with the ones in the substrate, and an
      integration over the thickness incorporated the properties of the metal layer
      into equations through the modification of material properties with the decaying
      indices of surface acoustic waves and the thickness of the metal layer. Using AT
      cut quartz crystal as the substrate, we present the effect of silver electrode
      layers of finite thickness on the phase velocity of propagating surface acoustic
      waves.

PMID- 16814835
TI  - Experimental researches of propagation of acoustic compression pulses in copper
      wires.
AB  - The results of experimental research related to the propagation of elastic
      plastic compression pulses in polycrystalline copper wires are presented. We have
      developed a technique of generating compression pulses with amplitudes of
      pressure exceeding 100 MPa; this essentially exceeds the elasticity limit of
      copper. This allows us to carry out the research for the propagation of
      compression pulses in copper wire (as simples). Significant influence of the
      pulse amplitude on its spectrum, velocity and absorption will be discussed. The
      experiments showed that as the amplitude of the pulse increase the pulses
      velocity is decreased and absorption will be increased. The pulse spectrum also
      changes correspondingly. The analysis and discussion of experimental results will
      be presented through the context.

PMID- 16814836
TI  - Application of Brillouin scattering to the local anisotropy and birefringence
      measurements of thin layers.
AB  - Brillouin scattering is an efficient nondestructive and noncontact measurement
      method to obtain the wave properties of thin layers at hypersonic frequencies.
      The reflection induced ThetaA (RIThetaA) scattering geometry enables the
      simultaneous measurement of the phonons, which propagate in each direction of
      wave vectors of q(Theta A) (propagation in the film plane) and q(180) (back
      scattering). Using this scattering geometry, we could observe the refractive
      indices and birefringence of the piezoelectric poly-vinylidene fluoride (PVDF)
      film as a function of temperature. By introducing the microscopic technique, the
      elastic anisotropy and refractive index measurements in the minute area of
      polycrystalline ZnO films were also performed.

PMID- 16814837
TI  - Piezoelectric diaphragm for vibration energy harvesting.
AB  - This paper presents a technique of electric energy generation using a
      mechanically excited unimorph piezoelectric membrane transducer. The electrical
      characteristics of the piezoelectric power generator are investigated under
      dynamic conditions. The electromechanical model of the generator is presented and
      used to predict its electrical performances. The experiments was performed with a
      piezoelectric actuator (shaker) moving a macroscopic 25 mm diameter piezoelectric
      membrane. A power of 0.65 mW was generated at the resonance frequency (1.71 kHz)
      across a 5.6 kOmega optimal resistor and for a 80 N force. A special electronic
      circuit has been conceived in order to increase the power harvested by the
      piezoelectric transducer. This electrical converter applies the SSHI
      (synchronized switch harvesting on inductor) technique, and leads to remarkable
      results: under the same actuation conditions the generated power reaches 1.7 mW,
      which is sufficient to supply a large range of low consumption sensors.

PMID- 16814838
TI  - Cortical visual function in the rd12 mouse model of Leber Congenital Amarousis
      (LCA) after gene replacement therapy to restore retinal function.
AB  - One eye of rd12 mice received a sub-retinal injection of a vector carrying normal
      human RPE65 cDNA at post-natal day 18, and at 6- and 13-months of age.
      Electroretinograms (ERGs) and visual-evoked potentials (VEPs) were recorded to
      luminance, and to spatially and temporally modulated stimuli to assess the
      consequences of delayed treatment on visual pathway function. Early treatment
      resulted in better overall retinal rescue and better rescue of cone-mediated
      function. VEPs to low temporal frequency luminance modulation were well preserved
      at all but the oldest treatment age and corresponded to predictions based on the
      amount of retinal rescue. In contrast, VEPs to high frequency spatially and
      temporally modulated stimuli were impaired even at the earliest age. These
      results provide further support that early treatment in human LCA will have the
      most hope for optimal visual performance.

PMID- 16814839
TI  - Do we all face the same risk when bathing in the estuary?
AB  - With the development of coastal areas, microbial water quality is an emerging
      public health issue though few studies have focused on risks according to age. A
      survey was undertaken of faecal contamination in relation to recreational
      activities in the Peel Harvey estuarine system, Western Australia. Levels of
      exposure to contaminated water were estimated though social surveys. Follow-up
      was also conducted to estimate the incidence of disease associated with bathing
      in the estuary. Pathogen levels exceeded the guideline values recommended by the
      World Health Organisation (WHO) at most locations throughout the year. The social
      survey provided information about exposure of the population in age groups. Only
      31% of the recreational users belonged to the healthy adult group upon which the
      WHO quantitative microbial risk assessment model is based. A correlation was
      established between microbial water quality and incidence of respiratory diseases
      for children as well as for adults. Exposure to recreational water increased the
      incidence of respiratory illnesses for the whole population almost by a factor 2.
      Behaviours which resulted in increased exposures were associated with increased
      incidence of illnesses were observed, particularly among children aged 11-15 yr,
      who exhibited the highest odd ratio (OR 4.23 [2.44-6.01], CI 95%, p=0.05). There
      is a need for combining epidemiology studies with risk assessment processes and
      complementing them with social surveys for understanding the risk of recreational
      activities to public health.

PMID- 16814840
TI  - Psychrophilic and mesophilic anaerobic digestion of brewery effluent: a
      comparative study.
AB  - Two expanded granular sludge bed-anaerobic filter (EGSB-AF) bioreactors (3.38 l
      active volume) were used to directly compare psychrophilic (15 degrees C),
      anaerobic digestion (PAD) to mesophilic (37 degrees C) anaerobic digestion (MAD)
      for the treatment of a brewery wastewater (chemical oxygen demand (COD)
      concentration of 3,136+/-891 mg l(-1)). Bioreactor performance was evaluated by
      COD removal efficiency and biogas yields at a range of hydraulic and organic
      loading rates. Specific methanogenic activity (SMA) assays were also employed to
      investigate the activity of the biomass in the bioreactors. No significant
      difference in the COD removal efficiencies (which ranged from 85-93%) were
      recorded between PAD and MAD during the 194-d trial at maximum organic and
      hydraulic loading rates of 4.47 kg m(-3) day(-1) and 1.33 m(3) m(-3) day(-1),
      respectively. In addition, the methane content (%) of the biogas was very
      similar. The volumetric biogas yield from the PAD bioreactor was approximately
      50% of that from the MAD bioreactor at an organic loading rate of 4.47 kg COD m(
      3) day(-3) and an applied liquid up-flow velocity (V(up)) of 2.5 m h(-1).
      Increasing the V(up) in the PAD bioreactor to 5 m h(-1) resulted in a volumetric
      biogas production rate of approximately 4.1 l d(-1) and a methane yield of 0.28 l
      CH(4) g(-1) COD d(-1), which were very similar to the MAD bioreactor. Significant
      and negligible biomass washout was observed in the mesophilic and psychrophilic
      systems, respectively, thus increasing the sludge loading rate applied to the
      former and underlining the robustness of the latter, which appeared underloaded.
      A psychrotolerant mesophilic, but not truly psychrophilic, biomass developed in
      the PAD bioreactor biomass, with comparable maximum SMA values to the MAD
      bioreactor biomass. PAD, therefore, was shown to be favourably comparable to MAD
      for brewery wastewater treatment and biogas generation.

PMID- 16814841
TI  - Land spreading of olive mill wastewater: effects on soil microbial activity and
      potential phytotoxicity.
AB  - Extremely high organic load and the toxic nature of olive mill wastewater (OMW)
      prevent their direct discharge into domestic wastewater treatment systems. In
      addition to the various treatment schemes designed for such wastewater,
      controlled land spreading of untreated OMW has been suggested as an alternative
      mean of disposal. A field study was conducted between October 2004 and September
      2005 to assess possible effects of OMW on soil microbial activity and potential
      phytotoxicity. The experiment was carried out in an organic orchard located on a
      Vertisol-type soil (Jezre'el Valley, Israel) and included two application levels
      of OMW (36 and 72m(3)ha(-1)). Total microbial counts, and to less extent the
      hydrolytic activity and soil respiration were increased following the high OMW
      application level. A bench-scale lab experiment showed that the rate of OMW
      mineralization was mainly dependent on the general status of soil activity and
      was not related to previous acclimatization of the soil microflora to OMW. Soil
      phytotoxicity (% germination and root elongation) was assessed in soil extracts
      of samples collected before and after each OMW application, using germinating
      cress (Lepidium sativum L.) seeds. We found direct short-term effect of OMW
      application on soil phytotoxicity. However, the soil was partly or completely
      recovered between successive applications. No further phytotoxicity was observed
      in treated soils as compared with control soil, 3 months after OMW application.
      Such short-term phytotoxicity was not in correlation with measured EC and total
      polyphenols in the soil extracts. Overall, the results of this study further
      support a safe controlled OMW spreading on lands that are not associated with
      sensitive aquifers.

PMID- 16814842
TI  - Reusing ethyl acetate and aqueous exhausted fractions of dry olive mill residue
      by saprobe fungi.
AB  - Some saprobe fungi (Phlebia radiata, Trametes versicolor, Coriolopsis rigida,
      Pycnoporus cinnabarinus, Fomes sclerodermus or Pleurotus pulmonarius) were able
      to bioconvert the ethyl acetate fraction (DEAF) and the corresponding aqueous
      exhausted fraction (EAF) of dry olive mill residue (DOR), reducing their
      phytotoxicity on Lepidium sativum seeds. Large amount of hydroxytyrosol together
      with other eight monomeric phenols were found in the native DEAF fraction, which
      represents a good source of antioxidants. P. radiata, T. versicolor and F.
      sclerodermus caused an effective phytotoxicity reduction of EAF in the
      concentration range of 25-3 gl(-1). In particular, in the range between 12.5 and
      3 gl(-1), the EAF samples inoculated with P. radiata and F. sclerodermus
      surprisingly stimulated the germinability of L. sativum, suggesting their use as
      a potential biofertilizer. This is the first report which showed the
      bioconversion of the above fractions in shorter time with respect to the previous
      findings concerning DOR. The possible implications of laccase in the decrease of
      DEAF and EAF phytotoxicity was also discussed.

PMID- 16814843
TI  - The concentrations and distribution of polycyclic musks in a typical cosmetic
      plant.
AB  - Polycyclic musks [cashmeran (DPMI), celestolide (ADBI), phantolide (AHMI),
      traseolide (ATII), tonalide (AHTN) and galaxolide (HHCB)] in the air, wastewater,
      sludge samples of a typical cosmetic plant were analyzed. DPMI, ADBI, HHCB and
      AHTN were found in all samples, and ATII was not found in any sample. HHCB and
      AHTN were the major components in all samples. The polycyclic musk concentrations
      were very high in the air of the cosmetic plant, and polycyclic musks were mostly
      contained in the gas phase at the percentage of 86.35-97.70%. Average polycyclic
      musk concentrations in effluent were high, and ranged from 0.62 to 32.06 microgl
      1. The removal efficiency during the active sludge wastewater treatment was also
      high, resulting from the adsorption of those compounds into the sludge. So the
      polycyclic musk concentrations were very high in the primary sludge and second
      sludge, and ranged from 1.78 to 92.45 mgkg-1 (dry), and from 2.87 to 65.67 mgkg-1
      (dry), respectively. Results suggested that the sludge needed to be further
      treated to make polycyclic musks less influence to the environment.

PMID- 16814844
TI  - Influence of pH on persulfate oxidation of TCE at ambient temperatures.
AB  - In situ chemical oxidation (ISCO) is a technology used for groundwater
      remediation. This laboratory study investigated the use of the oxidant sodium
      persulfate for the chemical oxidation of trichloroethylene (TCE) at near ambient
      temperatures (10, 20 and 30 degrees C) to determine the influence of pH (pH=4, 7
      and 9) on the reaction rate (i.e., pseudo-first-order rate constants) over the
      range of temperatures utilized. TCE solutions (60 mg l(-1); 0.46 mM) were
      prepared in phosphate buffered RO water and a fixed persulfate/TCE molar ratio of
      50/1 was employed in all tests. Half-lives of TCE degradation at 10, 20 and 30
      degrees C (pH 7) were 115.5, 35.0 and 5.5h, respectively. Maximum TCE degradation
      occurred at pH 7. Lowering system pH resulted in a greater decrease in TCE
      degradation rates than increasing system pH. Radical scavenging tests used to
      identify predominant radical species suggested that the sulfate radical (SO(4)(.
      )) predominates under acidic conditions and the hydroxyl radical (.OH)
      predominates under basic conditions. In a side by side comparison of TCE
      degradation in a groundwater vs. unbuffered RO water it was demonstrated that
      when the system pH is buffered to near neutral pH conditions due to the presence
      of natural occurring groundwater constituents that the TCE degradation rate is
      higher than in unbuffered RO water where the system pH dropped from 5.9 to 2.8.
      The results of this study suggest that in a field application of ISCO, pH should
      be monitored and adjusted to near neutral if necessary.

PMID- 16814845
TI  - Polybrominated diphenyl ethers (PBDEs) in sediment and bivalves from Korean
      coastal waters.
AB  - Concentrations of polybrominated diphenyl ethers (PBDEs) were determined in
      sediment and bivalves collected from 25 coastal locations in Korea. Twenty major
      PBDE congeners were found in all sediment and bivalve samples. SigmaPBDE20
      concentrations ranged from 0.45 to 494 ng/g, dry weight (average 27.8 ng/g dry
      weight) in sediments, and from 0.38 to 9.19 ng/g, wet weight (average 2.94 ng/g
      wet weight) in bivalves. The highest concentrations were found at locations near
      industrial complexes and large harbors, suggesting that human activities
      contribute to PBDEs contamination in Korean coastal environment. PBDE
      concentrations measured in our study, excluding BDE congener 209 (deca-BDE), in
      sediment and bivalves were lower than those reported from other countries;
      whereas BDE 209 concentrations were comparable to or higher than those reported
      from other countries. The predominant PBDE congener in sediments and bivalves was
      deca-BDE, which accounted for >90% and >60% of the total PBDE concentrations in
      sediment and bivalves, respectively. This is consistent with high consumption of
      deca-BDE for the flame-retardant market in Korea. Significant correlations
      existed among BDEs 28, 47, 99, 100, 153 and 154 in sediments and bivalves;
      however, BDEs 183 and 209 showed little correlation compared with less highly
      brominated congeners.

PMID- 16814846
TI  - Lead contamination of an old shooting range affecting the local ecosystem--A case
      study with a holistic approach.
AB  - The aim of this case study was to uncover the consequences of lead pellet-derived
      heavy lead contamination at a cast-off shooting range in southern Finland,
      covering aspects from soil chemistry and biology up to ecosystem level. The
      observed changes in the soil properties of the most contaminated areas suggest
      that the contamination may be disturbing processes of decomposition and nutrient
      mineralisation. Also two functionally important groups of soil organisms,
      microbes (as analysed using the PLFA analysis) and enchytraeid worms, were
      negatively affected by the contamination. Furthermore, there was an indication of
      reduced pine litter production at the contaminated areas. On the other hand, lead
      contamination appears not to have affected pine growth or soil-dwelling nematodes
      and microarthropods, and the general outlook of the whole ecosystem is that of a
      healthy forest. Thus, the boreal forest ecosystem studied as a whole appears to
      bear strong resistance to contamination, despite negative effects of lead on many
      of its components. This resistance may result from e.g. low bioavailability of
      lead, avoidance of the most contaminated soil horizons and microsites by the
      organisms, and functional redundancy and development of lead-tolerant populations
      amongst the organisms. The relative importance of these factors and the
      mechanisms behind them will be investigated in forthcoming studies.

PMID- 16814847
TI  - Long-term trends in accumulated metals (Cd, Cu and Zn) and metallothionein in
      bivalves from lakes within a smelter-impacted region.
AB  - Temporal monitoring studies are needed to detect long-term trends in ecosystem
      health. In the present study, we tested metallothionein (MT) as a potential
      biomarker for long-term variations in trace metal levels in lakes subject to
      atmospheric metal inputs from a nearby copper smelter. Over a 13-year period, we
      estimated on several occasions ambient free Cd2+, Cu2+ and Zn2+ concentrations at
      the sediment-water interface in six lakes with contrasting metal levels, and
      measured metal and metallothionein concentrations in gills of bivalves (Pyganodon
      grandis) living in these lakes. All but one of the study lakes had comparable
      drainage ratios, so inter-lake differences in hydrological export of metals from
      contaminated watersheds to receiving waters were likely minimal. Declines in the
      metal emissions from the smelter (especially for Cd and Zn) during the 1980s led
      to appreciable decreases in both calculated free Cd2+ ion concentrations in the
      study lakes (-59+/-21% between 1989 and 1998) and accumulated Cd levels in their
      clam populations (-46+/-12% between 1989 and 2002). Taking all lakes into
      account, MT concentrations in bivalves have comparatively dropped by 44% (+/-10%)
      since 1989. In contrast to what we found for Cd, there were no significant
      reductions in the calculated free Cu2+ and Zn2+ concentrations in the various
      lakes during our study period (-2 and -10%, respectively, with 95% confidence
      intervals spanning zero). Overall, observed decreases in MT in bivalves over time
      were best correlated with similar decreases in both ambient and accumulated Cd
      levels (r = 0.77, P = 0.0003 and r = 0.79, P < 0.0001, respectively, both P
      values corrected for temporal autocorrelation), suggesting that long-term trends
      in gill MT concentrations in P. grandis may be useful as predictors of temporal
      changes in environmental Cd contamination in lakes.

PMID- 16814848
TI  - A novel process utilizing subcritical water and nitrilotriacetic acid to extract
      hazardous elements from MSW incinerator fly ash.
AB  - An effective process for hazardous element extraction from municipal solid waste
      incinerator fly ash was developed. The key trait of the process was to extract
      most of the hazardous elements out of the ash but leave Ca and Si inside the
      residue. In the extraction process, the ash was firstly pre-washed with water,
      then subjected to subcritical water (SC water) treatment and nitrilotriacetic
      acid (NTA) extraction. SEM images indicated that SC water is strong enough to
      destroy the ash particles, thus greatly improving hazardous elements extraction
      efficiency in the subsequent NTA extraction process. The extraction percentages
      for Cr, As, Se, Cd and Pb under SC water+NTA treatment were around 2-6 times
      higher than those treated by NTA at room conditions. The preferable SC treatment
      temperature was 573 K and the treatment time was 3 h. The optimum NTA
      concentration, vibration time and liquid/solid ratio were 0.8 M, 5 h and 10:1
      (ml/g), respectively. Furthermore, it was found that introduction of a suitable
      amount of sulfuric acid into the extraction solution could extract more than 90%
      of most of the hazardous elements out of the ash.

PMID- 16814849
TI  - A methodology for ranking and hazard identification of xenobiotic organic
      compounds in urban stormwater.
AB  - The paper presents a novel methodology (RICH, Ranking and Identification of
      Chemical Hazards) for ranking and identification of xenobiotic organic compounds
      of environmental concern in stormwater discharged to surface water. The RICH
      method is illustrated as a funnel fitted with different filters that sort out
      problematic and hazardous compounds based on inherent physico-chemical and
      biological properties. The outcomes of the RICH procedure are separate lists for
      both water phase and solid phase associated compounds. These lists comprise: a
      justified list of compounds which can be disregarded in hazard/risk assessments,
      a justified list of stormwater priority pollutants which must be included in
      hazard/risk assessments, and a list of compounds which may be present in
      discharged stormwater, but cannot be evaluated due to lack of data. The procedure
      was applied to 233 xenobiotic organic chemicals (XOCs) of relevance for
      stormwater. Of these 233 compounds, 121 compounds were found to be priority
      pollutants with regard to solids phases (i.e. suspended solids, soil, or
      sediments) when stormwater is discharged to surface water and 56 compounds were
      found to be priority pollutants with regard to the water phase. For 11% of the
      potential stormwater priority pollutants the screening procedure could not be
      carried out due to lack of data on basic physico-chemical properties and/or data
      on bioaccumulation, resistance to biodegradation, and ecotoxicity. The tiered
      approach applied in the RICH procedure and the focus on the phases relevant for
      monitoring or risk assessment in the aquatic environment refines the list of
      "compounds of concern" when compared to the outcome of existing classification
      schemes. In this paper the RICH procedure is focused on effects in the aquatic
      environment exemplified with xenobiotic organic compounds (XOCs) found in urban
      stormwater, but it may be transferred to other environmental compartments and
      problems. Thus, the RICH procedure can be used as a stand-alone tool for
      selection of potential priority pollutants or it can be integrated in larger
      priority setting frameworks.

PMID- 16814850
TI  - Descriptions in the peer-reviewed literature of the results of phase 2
      chemotherapy trials involving gynecologic malignancies: a call for greater
      objectivity.

PMID- 16814851
TI  - Primary yolk sac tumor concomitant with carcinosarcoma originating from the
      endometrium: case report.
AB  - BACKGROUND: A primary yolk sac tumor (YST) with carcinosarcoma originating from
      the endometrium is extremely rare, to our knowledge, this is the third documented
      instance. Several hypotheses exist is to its histogenesis. CASE: A 65-year-old
      Japanese woman was diagnosed with a uterine malignancy and underwent surgical
      treatment and chemotherapy. The postoperative diagnosis was primary
      carcinosarcoma concomitant with a YST of the uterus. Immunohistochemical staining
      revealed that the tumor area suspected to be a YST was positive for alpha
      fetoprotein. CONCLUSION: We report a case of carcinosarcoma concomitant with a
      YST of uterus. This case is the third documented instance of a YST with
      concomitant with carcinosarcoma originating from the endometrium. The
      histogenesis in this case is suggests aberrantly differentiated somatic cells.

PMID- 16814852
TI  - Squamous cell carcinoma with sarcomatoid features of the vulva: a case report and
      review of literature.
AB  - BACKGROUND: A squamous cell carcinoma with sarcomatoid features of the vulva is
      an extremely rare malignancy of the female genital tract. This type of tumor is
      known to grow rapidly and associated with poorer clinical outcomes than those of
      squamous cell carcinoma of the vulva. CASES: A 43-year-old woman presented to our
      institute with a 4-month history of an aggravated vulvar mass. A radical local
      excision, bilateral inguinal lymph node dissection and laparoscopic assisted
      vaginal hysterectomy were performed. The FIGO stage of the vulvar cancer was
      stage II (T(2)N(0)M(0)) and the pathologic finding was consistent with a poorly
      differentiated squamous cell carcinoma with extensive sarcomatoid features. No
      further treatment was given and there was no clinical evidence of recurrence
      during the 2 years of follow-up. CONCLUSION: A squamous cell carcinoma with
      sarcomatoid features of the vulva is a tumor with aggressive biological behavior.
      To date, there have been only 15 cases of this disease reported in the
      literature. So, a collection and close study of these cases would be extremely
      useful in singling out and identifying the best treatment possible for this type
      of tumor.

PMID- 16814853
TI  - Cocaine self-administration under variable-dose schedules in squirrel monkeys.
AB  - Squirrel monkeys self-administered cocaine under a variable-dose schedule, with
      the dose varied from injection to injection. As in earlier studies with rats,
      post-injection pauses varied as a monotonic function of dose, allowing a cocaine
      dose-effect curve to be obtained during each session. These curves were shifted
      by pretreatment with dopamine antagonists, demonstrating that this procedure may
      provide an efficient means of evaluating treatments that affect drug self
      administration. However, drug intake eventually became "dysregulated" after
      extensive training (100-300 sessions), with relatively short pauses following all
      doses. Dose-sensitivity was restored by adding a 60-s timeout period after each
      injection, suggesting that dysregulation occurred because the monkeys developed a
      tendency to self-administer another injection before the previous injection had
      been adequately distributed. Finally, when the response requirement under the
      variable-dose schedule was increased from 1 to 10, both the post-injection pause
      and the rate of responding following the pause ("run rates") were found to vary
      with dose. The dose-dependency of run rates suggests that post-injection pauses
      reflect not only motivational factors, such as satiety, but also the direct
      effects of cocaine on leverpressing.

PMID- 16814854
TI  - Seasonal variations of fecal progesterone and 17beta-estradiol in captive female
      black-handed spider monkeys (Ateles geoffroyi).
AB  - A number of studies in free-ranging and captive spider monkeys (Ateles spp.) have
      shown that this genus is able to reproduce throughout the entire year.
      Nonetheless, it is still controversial whether births, and therefore conceptions,
      tend to be more frequent during certain seasons. In the present study, we
      monitored changes in fecal 17beta-estradiol and progesterone for approximately 1
      years in five female black-handed spider monkeys (Ateles geoffroyi) kept in
      captivity in Mexico City. The objective was to determine whether hormone
      concentrations and menstrual cycles of summer and autumn accounted for a greater
      chance of conception than those of winter and spring, consistent with birth
      patterns previously reported. We collected fecal samples from the five monkeys
      almost daily for 1 year (March 2004 to February 2005) and used radioimmunoassay
      of fecal extracts to determine concentrations of 17beta-estradiol and
      progesterone. Concurrently, menstrual cycle phases were determined by cytological
      evaluation of vaginal swabs. Periovulatory 17beta-estradiol concentrations were
      significantly higher in autumn than in winter, spring or summer. Moreover, as
      evidenced by progesterone peaks, most of the summer-autumn menstrual cycles were
      ovulatory; in contrast, most of the winter and spring cycles were anovulatory. In
      conclusion, our data supported the notion that, although not a strictly seasonal
      reproducer, the black-handed spider monkey is more likely to conceive at the end
      of the rainy season and throughout autumn.

PMID- 16814855
TI  - Relative importance of hydrocarbon pollutants, salinity and tidal height in
      colonization of oyster reefs.
AB  - The relative effects of hydrocarbon pollutants, salinity and tidal height on the
      invertebrates and fish that inhabit oyster reefs were studied along the Louisiana
      Gulf of Mexico coastline. Dried oyster shell (cultch) was first exposed to crude
      oil in the laboratory. In a series of experiments, plastic trays filled with
      control and oil-exposed cultch were then deployed at two locations differing in
      salinity, in two seasons and at two tidal levels. In experiments on hydrocarbon,
      salinity, and seasonal effects, trays were colonized for one month. To examine
      the effects of colonization time, half of the trays were retrieved after two and
      the rest after five weeks. Salinity dramatically affected oyster reef
      assemblages, with species richness and total abundance halved at the estuarine
      site. Hydrocarbon effects were less prominent, whether cultch was dosed with
      light or heavy crude oil. The sub-tidal site had higher colonization rates, but
      colonization interval did not affect colonization, and seasonal differences
      occurred only at the higher-diversity, sub-tidal site. To determine effects of
      cleaners, Corexit 9580 was applied alone and with oil on cultch, and trays were
      colonized for one month. At high concentrations, the cleaner ameliorated
      hydrocarbon effects. In general, hydrocarbon effects were less prominent than
      salinity and aerial exposure in explaining colonization of oyster reef
      assemblages. Gas chromatography/mass spectrometry analysis of oyster shells after
      one month immersion revealed considerable losses of oil, especially with higher
      flow at the inter-tidal site. Sediment on shell also diluted oil. We argue that
      oyster reef assemblages should recover from small-scale spills, unless they occur
      during periods of reproduction and dispersal.

PMID- 16814856
TI  - In situ localization and substrate specificity of earthworm protease-II and
      protease-III-1 from Eisenia fetida.
AB  - Recently, the function in fibrinolysis of earthworm proteases has been studied.
      In our experiments, earthworm protease-II (EfP-II) and earthworm protease-III-1
      (EfP-III-1) were isolated and purified from Eisenia fetida. As shown by the assay
      of sections of the earthworm on fibrin plates, the enzymic activity was mainly
      detected around the clitellum. In the presence of anti-EfP-II or anti-EfP-III-1
      serum, the immunological signals of the two isozymes were clearly found in the
      anterior alimentary mucosa, suggesting that EfP-II and -III-1 are localized and
      expressed in intestinal epithelial cells. The Michaelis-Menten constant (K(m))
      for EfP-III-1 reacting with BAEE is smaller (1.7x10(-5)M) in comparison with the
      K(m) values of other substrates such as Chromozym-Try and -TH (3.3-6.0x10(-5)M).
      This indicates that EfP-III-1 is a trypsin-like protein. EfP-II shows a strong
      trypsin-like, moderate elastase-like and weak chymotrypsin-like serine function.
      The relative broad substrate specificity of EfP-II and EfP-III-1 is consistent
      with their localization in the anterior alimentary canal where different micro
      organisms and ingested proteins require to be digested.

PMID- 16814857
TI  - In vitro studies of annulus fibrosus disc cell attachment, differentiation and
      matrix production on PDLLA/45S5 Bioglass composite films.
AB  - The aim of this study was to investigate the potential of using PDLLA/45S5 (PDLLA
      -poly(D,L-lactide)) Bioglass composite films for the culture of annulus fibrosus
      (AF) cells in vitro with a view to a tissue engineering application. PDLLA films
      incorporated with different percentages (0, 5 and 30 (wt%)) of Bioglass particles
      were prepared by solvent casting and characterized by scanning electron
      microscopy (SEM), water contact angle and white-light interferometry. Bovine AF
      cell morphology and attachment were analysed using SEM. Cytoskeletal organization
      was determined by actin labelling with FITC-phalloidin using fluorescence
      microscopy. The amount of sulphated glycosaminoglycan (sGAG) and collagen
      produced by AF cells were quantified using the 1,9-dimethylmethylene blue (DMMB)
      and Sircol assays after 4 weeks in culture. Composite films of PDLLA filled with
      Bioglass are an appropriate substrate for annulus cells and these films promote
      the production of an extracellular matrix (ECM) containing abundant sGAGs and
      collagen. These findings provide a basis for the understanding of the production
      of ECM molecules by cells cultured on 2D PDLLA/45S5 Bioglass composite films. The
      results will provide new insights into the design and development of composites
      containing Bioglass and resorbable polymers as scaffolds for intervertebral disc
      tissue repair.

PMID- 16814858
TI  - The effect of topographic characteristics on cell migration velocity.
AB  - The migration of cells on structured surfaces is known to be affected by its
      surface topography. Although the effects of topography have been extensively
      investigated the crucial parameters determining the cell-surface reaction are
      largely unknown. The present study was performed to describe and to define the
      role of groove/elevation (ridge) dimensions at the micrometre scale on fibroblast
      cell migration by correlating cell shape, migration angle alpha, cell orientation
      beta and velocity with these dimensions. For this a quantitative method was
      developed. We could show that the surface structures significantly influenced
      migration direction alpha, cell orientation beta and mean velocity, as well as
      migration speed in the directions parallel and perpendicular to the
      grooves/elevations in a surface structure dependant way. Cell migration velocity
      parallel, respectively, perpendicular to the structures was significantly
      affected by the geometries and dimensions of the substratum. Surface structures
      were not able to significantly affect distribution patterns of cell shapes.
      Overall, it could be shown that differently structured surfaces influenced the
      cells but no crucial feature could be clearly identified, suggesting that the
      reaction of the surface structure might be far more complex than generally is
      assumed.

PMID- 16814859
TI  - Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and
      co-cultures.
AB  - Bioengineering approaches, such as co-cultures of multiple cell types, that aim
      to mimic the physiological microenvironment may be beneficial for optimizing cell
      function and for engineering tissues in vitro. This study describes a novel
      method for preparing a spheroid microarray on microfabricated hydrogels, alone or
      in co-cultures. Photocrosslinkable chitosan was synthesized and utilized for
      fabricating hydrogel microstructures through a micromolding process. The chitosan
      surface was initially cell repellent but became increasingly cell adhesive over
      time. By using this unique property of chitosan hydrogels, it was possible to
      generate patterned co-cultures of spheroids and support cells. In this scheme,
      cells were initially microarrayed within low shear stress regions of microwells.
      Human hepatoblastoma cells, Hep G2, seeded in these wells formed spheroids with
      controlled sizes and shapes and stably secreted albumin during the culture
      period. The change of cell adhesive properties in the chitosan surface
      facilitated the adhesion and growth of a second cell type, NIH-3T3 fibroblast,
      and therefore enabled co-cultures of hepatocyte spheroids and fibroblast
      monolayers. This co-culture system could be a useful platform for studying
      heterotypic cell-cell interactions, for drug screening, and for developing
      implantable bioartificial organs.

PMID- 16814860
TI  - Temporary blast reduction after immunoglobulin administration for congenital
      cytomegalovirus infection masking infant leukemia with cryptic MLL rearrangement.
AB  - Differentiation between reactive bone marrow suppression due to viral infection
      and early stages of leukemia can be difficult particularly in young infants. We
      report on a 2-month-old girl presenting with pancytopenia and positive markers
      for congenital cytomegalovirus (CMV) infection. Definitive diagnosis of
      coexisting pro-B cell infant leukemia with cryptic MLL rearrangement was delayed
      by the transient regeneration of normal hematopoiesis and reduction of abnormal
      blastoid cells in the bone marrow following immunoglobulin administration.
      Molecular diagnosis could only be established using interphase fluorescence in
      situ hybridization (FISH) analysis which may be considered as a valuable
      additional diagnostic tool in similar cases.

PMID- 16814861
TI  - Absence of renal lesions in C57BL/KaLwRij mice with advanced myeloma due to 5T2MM
      cells.
AB  - Renal failure is one of the main complications in multiple myeloma (MM) and
      histopathological lesions are due to light chains accumulation in the kidney. The
      5T2MM mouse model closely mimics osteolytic lesions observed in clinics. We
      studied the occurrence of pathological changes in the kidney of mice inoculated
      with 5T2MM myeloma cells. No renal lesions due to light chain deposition were
      observed after histological, immunological staining and dosage of creatinine in
      serum and urine. PTH levels decreased in 5T2MM mice, confirming the absence of
      secondary hyperparathyroidism. Osteolytic lesions appear to be the unique
      consequence of 5T2MM cells inoculation.

PMID- 16814862
TI  - Strategies for targeting T-cells in allergic diseases and asthma.
AB  - T helper (Th) 2 lymphocytes play a crucial role in the initiation, progression
      and persistence of allergic diseases, including asthma. Drugs that interfere with
      the activation of T-cells or more selectively Th2-specific signaling molecules
      and drugs that prevent the selective migration into lung tissue are promising
      novel strategies for the treatment of allergic asthma. Although the mainstay
      asthma therapy of inhaled glucocorticoids is rather effective, targeting Th2
      cells may be an important alternative in childhood. Regulatory T-cells (Treg
      cells) have a physiological role in protection of unwanted immune responses to
      auto-antigens and allergens. Literature data indicate that an imbalance between
      Th2 and Treg cells may underlie development and disease expression of allergic
      asthma. Drugs or immunotherapies that stimulate these counter-Treg cells may
      limit aberrant Th2 responses leading to suppression of symptoms. Furthermore,
      these types of treatments may offer the perspective of disease modification and
      long-term relief of symptoms.

PMID- 16814863
TI  - 'Relaxin' the stiffened heart and arteries: the therapeutic potential for relaxin
      in the treatment of cardiovascular disease.
AB  - Although originally characterised as a reproductive hormone, relaxin has emerged
      as a multi-functional endocrine and paracrine factor that plays a number of
      important roles in several organs, including the normal and diseased
      cardiovascular system. The recent discovery of the H3/relaxin-3 gene, and the
      elusive receptors for relaxin (Relaxin family peptide receptor; RXFP1) and
      relaxin-3 (RXFP3/RXFP4) have led to the re-classification of a distinct relaxin
      peptide/receptor family. Additionally, the identification of relaxin and RXFP1
      mRNA and/or relaxin binding sites in the heart and blood vessels has confirmed
      that the cardiovascular system is a target for relaxin peptides. While evidence
      for the production of relaxins within the cardiovascular system is limited,
      several studies have established that the relaxin genes are upregulated in the
      diseased human and rodent heart where they likely act as cardioprotective agents.
      The ability of relaxin to protect the heart is most likely mediated via its
      antifibrotic, anti-hypertrophic, anti-inflammatory and vasodilatory actions, but
      it may also directly stimulate myocardial regeneration and repair. This review
      describes relaxin and its primary receptor (RXFP1) in relation to the roles and
      effects of relaxin in the normal and pathological cardiovascular system. It is
      becoming increasingly clear that relaxin has a number of diverse physiological
      and pathological roles in the cardiovascular system that may have important
      therapeutic and clinical implications.

PMID- 16814866
TI  - Comparison of the effects of selected chalcones, dihydrochalcones and some cyclic
      flavonoids on mitochondrial outer membrane determined by fluorescence
      spectroscopy.
AB  - The effect on mitochondrial outer membrane of 4-hydroxychalcone (1), the cyclic
      chalcone analogues E-2-(4'-hydroxybenzylidene)-1-indanone (2a) and E-2-(4'
      hydroxybenzylidene)-1-tetralone (2b), the dihydrochalcones phloretin (3a) and
      phloridzin (3b), the flavanones naringenin (4a) and naringin (4b), and the
      flavonol quercetin (5) was investigated by fluorescence spectroscopy. Excitation
      and emission fluorescence spectra of each flavonoid and synthetic analogue were
      recorded in respiration medium containing 1 mM succinate. Initial interaction of
      the compounds with the outer mitochondrial membrane was investigated by recording
      their fluorescence polarization in the presence of rat liver mitochondria. Most
      of the compounds displayed an elevated fluorescence polarization on mixing with
      mitochondria at the zero time point. During the investigated 20 min period the
      initial fluorescence polarization values remained constant (1, 2a), or a gradual
      depression of the measured polarization values could be observed (2b, 3a, 4b, 5).
      In the case of naringenin (4a), however, similar to the previously investigated
      seven-membered cyclic chalcone analogue E-2-(4 -methoxybenzylidene)-1
      benzosuberone, a slight, continuous increase of fluorescence polarization could
      be detected during the 20 min experiment. Phloridzin (3b) showed an increased
      fluorescence polarization in first 10 min, which was slightly depressed by the 20
      min time point.

PMID- 16814865
TI  - Properties of the Group IV phospholipase A2 family.
AB  - The Group IV phospholipase A2 family is comprised of six intracellular enzymes
      commonly called cytosolic phospholipase A2 (cPLA2) alpha, cPLA2beta, cPLA2gamma,
      cPLA2delta, cPLA2epsilon and cPLA2zeta. They are most homologous to phospholipase
      A and phospholipase B/lysophospholipases of filamentous fungi particularly in
      regions containing conserved residues involved in catalysis. However, a number of
      other serine acylhydrolases (patatin, Group VI PLA2s, Pseudomonas aeruginosa ExoU
      and NTE) contain the Ser/Asp catalytic dyad characteristic of Group IV PLA2s, and
      recent structural analysis of patatin has confirmed its structural similarity to
      cPLA2alpha. A characteristic of all these serine acylhydrolases is their ability
      to carry out multiple reactions to varying degrees (PLA2, PLA1, lysophospholipase
      and transacylase activities). cPLA2alpha, the most extensively studied Group IV
      PLA2, is widely expressed in mammalian cells and mediates the production of
      functionally diverse lipid products in response to extracellular stimuli. It has
      PLA2 and lysophospholipase activities and is the only PLA2 that has specificity
      for phospholipid substrates containing arachidonic acid. Because of its role in
      initiating agonist-induced release of arachidonic acid for the production of
      eicosanoids, cPLA2alpha activation is important in regulating normal and
      pathological processes in a variety of tissues. Current information available
      about the biochemical properties and tissue distribution of other Group IV PLA2s
      suggests they may have distinct mechanisms of regulation and functional roles.

PMID- 16814864
TI  - Low dose acute alcohol effects on GABA A receptor subtypes.
AB  - GABA(A) receptors (GABA(A)Rs) are the main inhibitory neurotransmitter receptors
      and have long been implicated in mediating at least part of the acute actions of
      ethanol. For example, ethanol and GABAergic drugs including barbiturates and
      benzodiazepines share many pharmacological properties. Besides the prototypical
      synaptic GABA(A)R subtypes, nonsynaptic GABA(A)Rs have recently emerged as
      important regulators of neuronal excitability. While high doses (> or =100 mM) of
      ethanol have been reported to enhance activity of most GABA(A)R subtypes, most
      abundant synaptic GABA(A)Rs are essentially insensitive to ethanol concentrations
      that occur during social ethanol consumption (< 30 mM). However, extrasynaptic
      delta and beta3 subunit-containing GABA(A)Rs, associated in the brain with alpha4
      or alpha6 subunits, are sensitive to low millimolar ethanol concentrations, as
      produced by drinking half a glass of wine. Additionally, we found that a mutation
      in the cerebellar alpha6 subunit (alpha6R100Q), initially reported in rats
      selectively bred for increased alcohol sensitivity, is sufficient to produce
      increased alcohol-induced motor impairment and further increases of alcohol
      sensitivity in recombinant alpha6beta3delta receptors. Furthermore, the
      behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement
      on alpha4/6/beta3delta receptors, without reducing GABA-induced currents. In
      binding assays alpha4beta3delta GABA(A)Rs bind [(3)H]Ro15-4513 with high
      affinity, and this binding is inhibited, in an apparently competitive fashion, by
      low ethanol concentrations, as well as analogs of Ro15-4513 that are active to
      antagonize ethanol or Ro15-4513's block of ethanol. We conclude that most low to
      moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15
      4513 binding sites on GABA(A)R subtypes.

PMID- 16814867
TI  - Empirical considerations regarding the use of ensemble-variance analysis of
      macroscopic currents.
AB  - Two fundamental properties of an ion channel are its single channel current (i)
      and its open probability (Po), which are most directly defined by single channel
      recordings. However, under some circumstances either practical limitations (e.g.,
      extreme voltages) or unique channel properties may preclude the use of single
      channel recordings for definition of such properties. As an alternative, the
      variance in macroscopic currents (non-stationary noise analysis or variance-mean
      analysis) has been exploited to define fundamental elementary properties of the
      underlying channels. Although some limitations of the variance-mean approach have
      been considered in previous work by others, here simulation methods were used to
      define the conditions under which variance analysis can be suitable for providing
      estimates of i and Po. Of particular interest is the extent to which reasonably
      reliable estimates of Po can be obtained, even under conditions of Po less than
      0.5. Empirically, the analysis indicates that, with sufficient numbers of sweeps
      and with constraints on initial estimates of i, reasonably reliable estimates of
      Po can be made down to 0.2. The impact of a number of other factors on the
      utility of variance-mean analysis are also considered, including effects of
      inactivation, filtering, and the consequences of particular gating schemes.

PMID- 16814868
TI  - Application of modified Sholl analysis to neuronal dendritic arborization of the
      cat spinal cord.
AB  - The drawings of Golgi-impregnated neurons from laminae I to VI in dorsal horn of
      the cat spinal cord were analysed morphometrically with a modified Sholl method
      of concentric circles. In order to advance the Sholl analysis of neuronal
      dendritic arborization patterns, we developed a new method of data presentation
      using polynomial regression and defining three parameters: the critical value of
      the circle radius (which defines the place of a possible circle intersecting
      maximum number of dendrites), the maximum number of dendritic intersections with
      the circles (counted for consecutive circles placed starting at the cell body to
      the border of the dendritic tree), and the mean value of the fitted polynomial
      function (which describes an average property concerning numbers of branches of
      dendritic tree over the whole region occupied by the dendritic arbor). For that
      purpose we also used the Sholl regression coefficient as well as the Schoenen
      ramification index. As an illustration of our model, we demonstrate that proposed
      modification of the Sholl method can successfully discriminate neuronal
      populations among different laminae of the cat spinal cord.

PMID- 16814869
TI  - Belief in dealing with depression alone: results from community surveys of
      adolescents and adults.
AB  - BACKGROUND: Community surveys have found that some people believe that it is
      better to deal with depression alone rather than seek help. However, there has
      been little research into the characteristics of this group. METHODS: Data were
      drawn from three Australian surveys: (1) a national survey of 1001 adults aged
      18+ years; (2) a school survey of 552 students aged 14-16 years from two regions;
      (3) a survey of 577 young people aged 12-17 years from the Melbourne region. In
      all three surveys, participants who believed it would be helpful to deal with
      depression alone were contrasted with those who believed it would be harmful in
      terms of sociodemographic characteristics, recognition of depression in a
      vignette, contact with people who experienced depression, beliefs about
      treatments, beliefs about using substances, beliefs about long-term outcomes, and
      beliefs about causes. RESULTS: In both adolescents and adults, belief in dealing
      with depression alone was associated with male gender, less favourable views
      about mental health professionals, more favourable views about using substances
      to deal with depression, and a more positive expectation about the outcome if
      treatment is not sought. Adolescents believing in dealing with depression alone
      had more favourable views about some potential helpers, such as church workers
      and pharmacists. In adults, but not adolescents, there was an association with
      the belief that depression is caused by personal weakness. LIMITATIONS: The
      surveys did not directly ask about reasons for believing that dealing with
      depression alone would be helpful and did not assess actual help-seeking.
      CONCLUSIONS: Factors encouraging dealing with depression alone are a belief that
      it is a self-limiting disorder, that substances are an effective way to deal with
      it and, in adults, that depression is due to personal weakness. Consistent with
      previous research, males are an important target group for encouraging seeking
      help to deal with depression.

PMID- 16814870
TI  - Chronic restraint stress modulates expression of genes in murine spleen.
AB  - Psychological and physical stress can alter the immune system in both humans and
      animals. We have reported that mice subjected to chronic 12-h daily physical
      restraint for 2 days showed dramatic apoptosis in splenocytes. To identify genes
      that contribute to the splenocyte apoptosis, we compare gene expression in the
      spleens of restrained and unstressed mice using oligo microarrays consisting of
      226 genes. We report here that mice subjected to chronic 12-h daily physical
      restraint for 2 days exhibited significantly altered expression of 50 of 226
      genes. These genes included pro-apoptotic genes. We selected 5 genes of interest
      and confirmed the microarray results by real-time PCR. In this study, we identify
      a potentially important component of pro-apoptotic activity in restraint stress
      and suggest a possible target for anti-apoptotic therapy to protect splenocytes
      against stress-induced apoptosis.

PMID- 16814872
TI  - Altered neuroantigen-specific cytokine secretion in a Th2 environment reduces
      experimental autoimmune encephalomyelitis.
AB  - Activation of Th2 cells suppresses clinical experimental autoimmune encephalitis
      (EAE), demyelination and expression of genes associated with Th1-mediated
      inflammation. Despite both reduced central nervous system inflammation and IFN
      gamma induced MHC class II expression by microglia, the composition of CNS
      infiltrates in Th2-protected mice were similar to mice with EAE. Analysis of the
      CNS infiltrating cells by flow cytometry suggests that protection did not
      correlate with abrogation of CD4+ T cell recruitment, preferential recruitment of
      donor Th2 cells or an increased frequency of CD25+ CD4+ T cells. By contrast,
      protection correlated with an increased frequency of neuroantigen-specific Th2
      cells infiltrating the CNS. These data suggest that a peripheral Th2 cytokine
      environment influences both potential antigen presenting cells as well as
      recruitment and/or retention of neuroAg-specific Th2 CD4+ T cells.

PMID- 16814871
TI  - Modulation of astrocyte proliferation by HIV-1: differential effects in
      productively infected, uninfected, and Nef-expressing cells.
AB  - Although quiescent in normal brain, reactive astrocytes can proliferate in
      various disorders. We examined the impact of HIV-1 on astrocyte proliferation in
      cultures exposed to VSVg env-pseudotyped HIV-1 which yields high levels of
      infection. HIV-1, while increasing the proliferation of uninfected (p24-)
      astrocytes, strongly inhibited proliferation of productively infected (p24+)
      cells. The cell cycle arrest was G1/S rather than G2/M, a type commonly
      attributed to Vpr. No clear role of Vpr or Nef could be identified. Adenovirus
      mediated expression of Nef (a model of "restricted" infection) induced M-phase
      arrest of astrocytes. We speculate that HIV-1 is a significant modulator of
      astrocyte proliferation in vivo.

PMID- 16814873
TI  - Survey of pediatric otolaryngologists: clinical practice trends used to prevent
      and treat blocked ventilation ear tubes in children.
AB  - OBJECTIVE: To estimate clinical impact of blocked tubes in children and to
      identify prevention/treatment trends. METHODS: A survey was sent to American
      Society of Pediatric Otolaryngology (ASPO) members via Internet. RESULTS: One
      hundred twenty two members of ASPO members responded (58%). Most clinicians saw
      their patients 4-8 weeks after surgery. The estimated blockage rate was between 0
      and 9% (despite the use of prophylactic drops applied perioperatively including
      those with antibiotics only (55%), antibiotic with steroids (36%) or decongestant
      drops (14%), respectively). Most clinicians opted to treat blocked tube with a
      course of drops applied at home (73% used drops over half the time). Those drops
      most commonly used included the following either alone or in combination for up
      to 14 days: antibiotics with steroids, antibiotics alone, or either 1.5 or 3%
      hydrogen peroxide. Fewer clinicians used suction and/or debridement under
      microscopic guidance to unblock the tube at the office visit. However, most
      clinicians agreed that microscopic debridement was more effective than a course
      of drops in opening blocked tubes (80% versus 70% estimated median success rate,
      respectively, p=0.0003). CONCLUSIONS: Approximately one half million sets of
      tubes (1,000,000 total tubes) are placed per year in North America. Based on
      results of this survey and those from the literature, 50,000 patients require
      treatment postoperatively because their tubes blocked (despite the use of
      prophylactic eardrops). This study identifies that a variety of treatments exist
      and confirms that further study is warranted to prevent postoperative tube
      blockage.

PMID- 16814874
TI  - Developmental delay and outcomes in paediatric cochlear implantation:
      implications for candidacy.
AB  - OBJECTIVE: Criteria for paediatric cochlear implant candidacy continue to evolve,
      as research indicates an increasingly broad range of children for whom the
      procedure can produce benefit. Children with difficulties in addition to their
      deafness, or global developmental delay, are not routinely excluded. The aim of
      this study is to explore the association between developmental delay in young
      paediatric cochlear implant candidates and progress with the device. MATERIALS
      AND METHODS: The study is a retrospective case series analysis of 32 children,
      aged between 1.2 and 2.8 years at pre-implant assessment. Children were assessed
      using the Schedule of Growing Skills II and IT-MAIS before implantation. Progress
      in speech perception and Speech Intelligibility was monitored using the E2L toy
      test and Speech Intelligibility Rating (SIR), respectively, 1 and 2 years after
      switch-on. RESULTS: Data were subjected to regression analyses, with either the
      E2L or SIR as the outcome variables, and variables derived from the Schedule of
      Growing Skills II (general development and cognitive functioning), IT-MAIS, age
      at switch-on and average aided hearing loss pre-implant as the predictor
      variables. In each analysis the strongest (and statistically significant)
      predictors of speech perception and Speech Intelligibility were the measures of
      general development and cognitive functioning, accounting for around 40% of the
      variance in outcomes. CONCLUSION: This study indicates the value of routinely
      assessing the general development of young paediatric cochlear implant
      candidates, as part of the pre-implant decision-making process. Significant
      developmental delay is predictive of poor outcomes, but children with a mild
      delay do make appreciable progress. Developmental assessment of young deaf
      children is therefore important in terms of candidacy decisions and counselling
      parents regarding potential benefit from a cochlear implant.

PMID- 16814875
TI  - Evaluation of speech intelligibility for children with cleft lip and palate by
      means of automatic speech recognition.
AB  - OBJECTIVE: Cleft lip and palate (CLP) may cause functional limitations even after
      adequate surgical and non-surgical treatment, speech disorders being one of them.
      Interindividually, they vary a lot, showing typical articulation specifics such
      as nasal emission and shift of articulation and therefore a diminished
      intelligibility. Until now, an objective means to determine and quantify the
      intelligibility does not exist. METHOD: An automatic speech recognition system, a
      new method, was applied on recordings of a standard test to evaluate articulation
      disorders (psycholinguistic analysis of speech disorders of children PLAKSS) of
      31 children at the age of 10.1+/-3.8 years. Two had an isolated cleft lip, 20 a
      unilateral cleft lip and palate, 4 a bilateral cleft lip and palate, and 5 an
      isolated cleft palate. The speech recognition system was trained with adults and
      children without speech disorders and adapted to the speech of children with CLP.
      In this study, the automatic speech evaluation focussed on the word accuracy
      which represents the percentage of correctly recognized words. Results were
      confronted to a perceptive evaluation of intelligibility that was performed by a
      panel of three experts. RESULTS: The automatic speech recognition yielded word
      accuracies between 1.2 and 75.8% (mean 48.0+/-19.6%). The word accuracy was
      lowest for children with isolated cleft palate (36.9+/-23.3) and highest for
      children with isolated cleft lip (72.8+/-2.9). For children with unilateral cleft
      lip and palate it was 48.0+/-18.6 and for children with bilateral cleft lip and
      palate 49.3+/-9.4. The automatic evaluation complied with the experts' subjective
      evaluation of intelligibility (p<0.01). The multi-rater kappa of the experts
      alone differed only slightly from the multi-rater kappa of experts and
      recognizer. CONCLUSION: Automatic speech recognition may serve as a good means to
      objectify and quantify global speech outcome of children with cleft lip and
      palate.

PMID- 16814876
TI  - Detection of Louping ill virus in clinical specimens from mammals and birds using
      TaqMan RT-PCR.
AB  - The identification of Louping ill virus (LIV) in clinical specimens has been
      routinely achieved by virus isolation using susceptible pig kidney cells and
      subsequent serological analysis. While this method is sensitive and detects
      infectious virus, it is relatively labour intensive and time-consuming. In view
      of the veterinary and potential medical importance of LIV, a rapid and precise
      detection method for routine use that employs the TaqMan reverse transcription
      polymerase chain reaction (RT-PCR) has been developed to detect LIV RNA extracted
      from field samples. The TaqMan assay was evaluated against virus isolation using
      22 cell culture grown LIV isolates, which had previously been partially
      characterised by sequencing, and material from 63 suspect field cases.
      Histopathological and/or serological reports were available for 39 of the suspect
      cases, providing additional diagnostic information to evaluate the results
      obtained from the TaqMan RT-PCR assay. The TaqMan assay was as sensitive as the
      cell culture infectious virus assay currently used and had the advantage that it
      was able to detect LIV in clinical specimens from which infectious virus could
      not be isolated possibly due to the presence of high levels of LIV antibody.

PMID- 16814878
TI  - Glucocorticoid receptors in lateral septum are involved in the modulation of the
      emotional sequelae induced by social defeat.
AB  - The current research studied the behavior adopted in the elevated plus maze (EPM)
      of rats previously subjected to a social defeat using the resident-intruder
      paradigm. One day after defeat, intruder animals exhibited an anxiogenic-like
      behavior in the EPM. In addition, we also evaluated the role of the
      corticosteroid receptor system (minerlocorticoid - MR - and glucocorticoid - GR -
      receptors) from the lateral septum (LS) on the anxiety generated by social
      defeat. The LS is an area of the aversive circuitry that is preferentially
      activated in passive defensive postures, and participates - together with other
      brain areas - in the modulation of aversive states. Intruder animals were infused
      into the LS with the MR or GR antagonist (ZK 91587 and RU 38486, respectively)
      and then submitted to social stress. All rats were tested in the EPM 1 day later.
      Only the administration of the GR antagonist, but not the MR antagonist, into the
      LS normalized the anxiogenic response induced by defeat. Furthermore, we examined
      whether a single injection of corticosterone (CS) could induce the same influence
      on the behavior in the EPM as that observed after social defeat. Moreover, we
      explored the effect of local infusions of MR or GR antagonists into the LS on the
      behavior exhibited by CS-treated rats in a subsequent EPM exposure. CS
      administration also exerted an increased anxiogenic-like behavior, which was
      normalized only by the local infusion of the GR antagonist. Based on these
      findings, we suggest that CS secreted by emotionally relevant stimuli acting via
      GR in LS plays an important role in the modulation of the emotional sequelae
      induced by social defeat.

PMID- 16814877
TI  - Development and comparison of genome detection assays for the diagnosis of foot
      and-mouth disease suspected clinical samples.
AB  - Detection of foot-and-mouth disease virus (FMDV) from clinical specimens by
      conventional sandwich enzyme-linked immunosorbent assay (ELISA) and virus
      isolation in cell culture is often compromised owing to limited sensitivity and
      inactivation during transit, respectively. A RT-PCR (oligoprobing) ELISA in both
      solid and aqueous phase hybridization formats targeting an across serotype
      conserved site at 3C-3D region was developed and its effectiveness was compared
      with that of the known targets at the IRES region. A non-isotopic RNA dot
      hybridization assay with colorimetric detection targeting both the IRES and the
      3D region were also validated, which is capable of handling high throughput
      samples with ease. RT-PCR (oligoprobing) ELISA and dot hybridization assay showed
      1000- and 10-fold greater sensitivity than the sandwich ELISA, respectively.
      Robustness of these diagnostic methods was explored by examining on sandwich
      ELISA-negative clinical samples. Both the assays developed in the present study
      were able to detect viral genomes in samples undetectable by conventional ELISA,
      thereby demonstrating 'proof of sensitivity'. Although the potential of these
      assays for providing definitive diagnosis in carrier hosts and in species where
      clinical disease is inapparent remains to be examined, nevertheless these assays
      can be adapted for comprehensive surveillance of foot-and-mouth disease in India.

PMID- 16814879
TI  - Effects of age-related hearing loss on startle reflex and prepulse inhibition in
      mice on pure and mixed C57BL and 129 genetic background.
AB  - The present study examined the developmental course of the age-related hearing
      loss and its consequences on the expression of acoustic startle reflex (ASR) and
      prepulse inhibition (PPI) generated by white-noise bursts in 129S2/SvPas (129)
      and C57BL/6J (C57) mouse strains and their F(1) hybrids. Auditory brainstem
      responses (ABR), ASR and PPI were assessed at various time points: 6, 28, 41 and
      94 weeks. Both parental strains showed marked ABR threshold shifts with age, with
      C57 mice having the most pronounced deficits. By contrast, the hybrids displayed
      only minor hearing loss with age. The time courses of ASR and PPI varied
      considerably between the mouse strains. From 6 to 41 weeks of age, ASR and PPI
      elicited by weak stimuli (70-90dB) increased in C57 mice, whereas the startle
      responses to intense stimuli (95-120dB) declined progressively. In 129 and hybrid
      mice, PPI levels remained relatively stable during the first year, but a
      progressive increase of ASR was observed in the hybrids for intense stimuli (95
      120dB). When animals reached 94 weeks of age, marked deterioration of ASR was
      observed in all strains, while deficits in PPI were only seen in 129 and C57
      mice. These findings show that the time course and the severity of the hearing
      loss vary considerably between 129, C57 strains and their hybrids, thus
      suggesting a marked heterogeneity in the genetic mechanisms underlying deafness
      in mice. They also demonstrate that the age-related hearing loss may have complex
      consequences on auditory behavioral performances depending of the severity of the
      deficits, the genetic background as well as the stimuli parameters.

PMID- 16814880
TI  - Increased ovarian follicular apoptosis in fathead minnows (Pimephales promelas)
      exposed to dietary methylmercury.
AB  - Exposure to environmentally relevant concentrations of dietary methylmercury
      impairs the reproduction of fish. Although specific mechanisms are unknown,
      recent research has linked altered reproduction in fish to the suppression of
      circulating levels of sex steroid hormones by methylmercury. We hypothesize that
      methylmercury induces apoptosis in steroidogenic gonadal cells in fish, thereby
      interfering with the synthesis of sex steroid hormones critical for the
      regulation of reproduction. To test this hypothesis, we chronically exposed
      fathead minnows (Pimephales promelas) to one of three diets contaminated with
      methylmercury: 0.06 microg Hg g(-1) (control), 0.87 microg Hg g(-1), and 3.93
      microg Hg g(-1) dry weight. Apoptosis was evaluated histologically in ovaries of
      female fathead minnows by terminal deoxynucleotidyl transferase (TdT)-mediated
      dUTP nick end labeling (TUNEL). Methylmercury significantly increased the number
      of apoptotic follicular cells in primary growth and cortical alveolus stage
      ovarian follicles. Ovarian follicular cells (i.e., granulosa, theca) are
      responsible for the production of 17beta-estradiol and other sex steroid
      hormones. Increased ovarian follicular apoptosis was related to suppressed 17beta
      estradiol concentrations and smaller ovary size of female fathead minnows. Our
      results suggest increased apoptosis of steroidogenic gonadal cells as a possible
      mechanism for the suppression of sex steroid hormones and ultimately the
      impairment of reproduction in fish exposed to methylmercury.

PMID- 16814881
TI  - Molecular properties and intracellular localization of rat liver nuclear scaffold
      protein P130.
AB  - We examined the molecular basis of rat P130, a nuclear scaffold protein, and its
      functions. P130 comprising 845 amino acid residues possesses several functional
      domains and yields an electrophoretically distinctive isoform, P123, by altering
      its phosphorylation status in association with translocation across the nuclear
      membrane and from the digitonin-extractable fraction of the nucleus to the
      nuclear scaffold. The functional domains, NLS, NES, and zinc-finger bearing DNA
      binding domains, ZF1 and ZF2, aid these translocations. P130 binds RNA through
      two RNA-binding domains (RB1 and RB2) similar to those of hnRNPs I and L.
      Microsome- and polysome-localized P130 and P123 were found in rat liver and Ac2F
      hepatoma cells. This localization required prior entry of P130 to the nucleus,
      but did not require RB1 and RB2. Thus, P130 initially purified from rat liver
      nuclear scaffold has the potential to play a variety of roles in biological
      events not only in the nuclear scaffold but also in various subcellular
      compartments. P130 (AB205483) is identical to matrin 3 (M63485 and BC062231),
      although the primary structure of rat matrin 3 has been revised, since it was
      first published.

PMID- 16814882
TI  - Coronary embolism causing myocardial infarction in a patient with mechanical
      aortic valve prosthesis.
AB  - Coronary embolism as a cause of myocardial infarction is an uncommon but
      important entity both in terms of aetiology and treatment. Previous cases of
      coronary emboli in association with prosthetic mechanical valves have been
      reported previously but the mechanism of pharmacology and lack of patient
      awareness of medication importance is quite unique in this case. A 65-year-old
      male presented to the emergency room with an anterior ST elevation myocardial
      infarction after 14 h of symptoms. Past medical history included aortic valve
      replacement with a mechanical tilting-disc valve 18 months earlier for
      symptomatic severe calcific aortic stenosis. Pre-operative coronary angiography
      revealed normal coronary arteries. On this occasion, coronary angiography
      revealed an occluded LAD with an embolic occlusion at the midpoint of the vessel.
      Successful PTCA and stenting of the lesion were performed. Amazingly, the patient
      had decided 1 year earlier to stop taking his warfarin medication. He had begun
      taking a new "herbal remedy" which was helping with his joint pains but the
      combination with warfarin was causing excessive bleeding each day after facial
      shaving. He therefore decided to abruptly stop taking his warfarin without any
      medical advice. Embolic myocardial infarction is underdiagnosed and it is
      important to diagnose the source of embolism and treat the cause. Patient
      education is vital in our battle to prevent this entity in high-risk patients as
      in our case.

PMID- 16814883
TI  - Percutaneous revascularization of chronic total occlusions: review of the role of
      invasive and non-invasive imaging modalities.
AB  - Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) has a
      lower success rate than PCI of non-occluded coronary stenosis. Failure to cross
      the occlusive lesion with a guide wire is the main cause of unsuccessful PCI of a
      CTO. Multi-imaging modalities may provide valuable information for PCI of CTO.
      This paper reviews the role of invasive and non-invasive imaging modalities such
      as intravascular ultrasound, optical coherent reflectometry, CT coronary
      angiography and cardiac magnetic resonance imaging in facilitating percutaneous
      coronary intervention of CTO.

PMID- 16814884
TI  - How to relevantly measure the relevance of published articles?

PMID- 16814885
TI  - MDCT evaluation of the right ventricle-pulmonary artery bypass stenosis in
      corrected tetralogy of Fallot.

PMID- 16814886
TI  - Spatial distribution of foot-and-mouth disease in Pakistan estimated using
      imperfect data.
AB  - We estimated the spatial distribution of foot-and-mouth disease (FMD) in
      Pakistan; we used a probability co-kriging model and the number of FMD outbreaks
      reported between 1996 and 2000 by Pakistan to the Office International des
      Epizooties. We used a k-Bessel model and small-ruminant and human densities as
      surrogate covariates for the population at risk and for livestock markets and
      movements, respectively. Compared to no or only one covariate, the co-kriging
      model with both densities provided the best fit to independently obtained data on
      the spatial distribution of virus isolations (P=0.57). The estimated probability
      of an FMD outbreak per 25km(2) cell ranged from 0.017 to 0.812, with the maximum
      relative probability of 47.8 (0.812/0.017). Areas with the highest relative
      probability of having an FMD outbreak were located in the Punjab region; this is
      a major animal-production area located along a traditional international animal
      trade route.

PMID- 16814887
TI  - Simulating Escherichia coli O157:H7 transmission to assess effectiveness of
      interventions in Dutch dairy-beef slaughterhouses.
AB  - Beef contamination with Escherichia coli O157:H7 (VTEC) is an important food
      safety issue. To investigate the effectiveness of interventions against VTEC in
      Dutch beef industrial slaughterhouses that slaughter 500 dairy cattle per day, a
      Monte Carlo simulation model was built. We examined seven carcass-antimicrobial
      interventions, namely: hot-water wash, lactic-acid rinse, trim, steam-vacuum,
      steam-pasteurization, hide-wash with ethanol and gamma irradiation, and their
      combinations. The estimated daily prevalence of contaminated beef-carcass
      quarters as the output of the model was 9.2%. Contaminated was defined as
      containing one or more CFU on the surface of a carcass quarter at the end of the
      quartering stage. Single interventions (except irradiation) could reduce the
      prevalence to from 6.2% to 1.7%, whereas the combination of interventions could
      lower it to from 1.2% to 0.1%. The most powerful intervention was irradiation,
      which could reduce the prevalence to <0.1%. The results of this study indicate
      that application of single interventions might be useful, although not
      sufficient. Hence, a combination of interventions along the slaughter process is
      the more promising approach to reduce the prevalence of contaminated beef
      quarters.

PMID- 16814888
TI  - Dissociation of physiology and behavior in PTSD.
AB  - We have previously reported that subjects with posttraumatic stress disorder
      (PTSD) differ from trauma controls in their ability to produce and withhold
      responses in the Stop-Signal Task depending on the motivational context as
      determined by financial reward. This experiment measured skin conductance and
      heart rate to assess autonomic changes accompanying these different patterns of
      behavior. Fowles hypothesized that heart rate would increase with behavioral
      activation and that increases in skin conductance would accompany behavioral
      inhibition. Both PTSD and comparison groups showed the expected behavioral
      changes in response to rewards, but they differed in their physiological
      responses. The subjects in the traumatized comparison group showed changes in
      skin conductance and heart rate consistent with Fowles' hypothesis and the
      observed changes in behavioral inhibition and activation. However, PTSD subjects
      showed no significant change in either physiological measure. These results
      demonstrate a dissociation between autonomic reactivity and motivated behavior in
      PTSD that may represent one aspect of emotional numbing.

PMID- 16814889
TI  - Increased cognitive load during simple and complex motor tasks in acute stage
      after stroke.
AB  - The aim of this study was to assess the activation of primary motor cortex,
      prefrontal cortex and parietal cortex during simple and complex motor tasks
      performed with the hemiparetic and non-hemiparetic hand. METHODS: Seven patients
      after stroke in the left brain hemisphere were included in the study. Functional
      magnetic resonance imaging (fMRI) was performed in the first and third week, and
      in three patients also three months after the stroke. RESULTS: Performance of
      both the simple and the complex tasks with the hemiparetic or non-hemiparetic
      hand resulted in activations of the motor cortex, prefrontal cortex and parietal
      cortex in majority of the consecutive fMRI sessions. Three months after the
      stroke fMRI data revealed reduced activation of primary motor cortex and parietal
      cortex in the contralesional hemisphere during the performance of the simple task
      by the hemiparetic hand. During the complex task, the reduction of activation was
      less prominent. CONCLUSIONS: Results of the present study suggest that in mildly
      impaired stroke patients a bilateral activation of prefrontal and parietal cortex
      may participate in the recovery process from stroke. The potential for
      measurement of cortical rehabilitation is discussed.

PMID- 16814891
TI  - Automated high-throughput immunomagnetic separation-PCR for detection of
      Mycobacterium avium subsp. paratuberculosis in bovine milk.
AB  - Two monoclonal antibody-mediated immunomagnetic separation PCR kits (AnDiaTec
      ParaTub-S IMS-PCR-ELISA and ParaTub-SL IMS-real time PCR) were developed and
      evaluated for the automated high-throughput detection of Mycobacterium avium
      subsp. paratuberculosis (M. paratuberculosis) in bulk milk of naturally infected
      dairy herds and made commercially available. M. paratuberculosis are first
      isolated from milk by high-throughput immunomagnetic bead separation using a
      completely automated magnetic particle pipetting robot within 45 min and released
      subsequently for analysis directly into PCR amplification mixtures for real time
      PCR or for PCR-ELISA. The threshold detection level and specificity of the tests
      were evaluated first with different M. paratuberculosis pure cultures and
      artificially contaminated (spiked) bulk milk samples. Both experiments proved a
      good detection limit, specificity and reliability of the tests that consistently
      detected 20 or less M. paratuberculosis organisms from cattle, deer and mufflon
      in 1 ml milk. Experiments with more than 200 bulk milk samples that were tested
      in parallel with the PCR methods and with the cultural method in a second
      evaluation study demonstrated that both PCR tests are superior to culture and
      sufficiently sensitive to detect single shedders in pooled milk samples. The
      experiments proved that the newly developed tests are sensitive, specific and
      fast, and thus for the first time allow the standardized large-scale routine M.
      paratuberculosis screening of bulk milk samples at acceptable costs.

PMID- 16814890
TI  - Spontaneously fermented millet product as a natural probiotic treatment for
      diarrhoea in young children: an intervention study in Northern Ghana.
AB  - Indigenous lactic acid fermented foods may have potential as probiotic treatment
      for diarrhoea, due to high levels of lactic acid bacteria. In this study the
      effect of a millet drink, spontaneously fermented by lactic acid bacteria, as a
      therapeutic agent among Ghanaian children with diarrhoea, was assessed. Children
      below 5 years of age coming to Northern Ghana health clinics for treatment of
      diarrhoea were randomised to two groups. Children of both groups received
      treatment for diarrhoea given at the local clinic. The intervention group in
      addition received up to 300 ml fermented millet drink (KSW) daily for 5 days
      after enrolment. The clinical outcome of diarrhoea and reported well-being were
      registered every day for the 5-day intervention and again 14 days after
      diagnosis. Among 184 children (mean age 17.4, standard deviation 11.3 months)
      included, no effects of the intervention were found with respect to stool
      frequency, stool consistency and duration of diarrhoea. However, KSW was
      associated with greater reported well-being 14 days after the start of the
      intervention (P=0.02). The fact that no effect of KSW on diarrhoea was observed
      could be because many children had a mild form of diarrhoea, and many were
      treated with antibiotics. Either this could have affected the lactic acid
      bacteria, or the lactic acid bacteria in KSW had no probiotic effects. It is
      speculated that the effect after two weeks could be due to a preventing effect of
      KSW on antibiotic-associated diarrhoea which could help reducing persistent
      diarrhoea.

PMID- 16814892
TI  - Characterisation of prototype Nurmi cultures using culture-based microbiological
      techniques and PCR-DGGE.
AB  - Undefined Nurmi-type cultures (NTCs) have been used successfully to prevent
      salmonella colonisation in poultry for decades. Such cultures are derived from
      the caecal contents of specific-pathogen-free birds and are administered via
      drinking water or spray application onto eggs in the hatchery. These cultures
      consist of many non-culturable and obligately anaerobic bacteria. Due to their
      undefined nature it is difficult to obtain approval from regulatory agencies to
      use these preparations as direct fed microbials for poultry. In this study, 10
      batches of prototype NTCs were produced using an identical protocol over a period
      of 2 years. Traditional microbiological techniques and a molecular culture
      independent methodology, polymerase chain reaction combined with denaturing
      gradient gel electrophoresis (PCR-DGGE), were applied to characterise these
      cultures and also to examine if the constituents of the NTCs were identical.
      Culture-dependent analysis of these cultures included plating on a variety of
      selective and semi-selective agars, examination of colony morphology, Gram
      staining and a series of biochemical tests (API, BioMerieux, France). Two sets of
      PCR-DGGE studies were performed. These involved the amplification of universal
      and subsequently lactic acid bacteria (LAB)-specific hypervariable regions of a
      16S rRNA gene by PCR. Resultant amplicons were subjected to DGGE. Sequence
      analysis was performed on subsequent bands present in resultant DGGE profiles
      using the Basic Local Alignment Search Tool (BLAST). Microbiological culturing
      techniques tended to isolate common probiotic bacterial species from the genera
      Lactobacillus, Lactococcus, Bifidobacterium, Enterococcus, Clostridium,
      Escherichia, Pediococcus and Enterobacterium as well as members of the genera,
      Actinomyces, Bacteroides, Propionibacterium, Capnocytophaga, Proteus, and
      Klebsiella. Bacteroides, Enterococcus, Escherichia, Brevibacterium, Klebsiella,
      Lactobacillus, Clostridium, Bacillus, Eubacterium, Serratia, Citrobacter,
      Enterobacter, Pectobacterium and Pantoea spp. in addition to unculturable
      bacteria were identified as constituents of the NTCs using universal PCR-DGGE
      analysis. A number of the sequences detected by LAB-specific PCR-DGGE were
      homologous to those of a number of Lactobacillus spp., including L. fermentum, L.
      pontis, L. crispatus, L. salivarius, L. casei, L. suntoryeus, L. vaginalis, L.
      gasseri, L. aviaries, L. johnsonii, L. acidophilus, and L. mucosae in addition to
      a range of unculturable lactobacilli. While NTCs are successful due to their
      complexity, the presence of members of Lactobacillus spp. amongst other probiotic
      genera, in these samples possibly lends to the success of the NTC cultures as
      probiotics or competitive exclusion products in poultry over the decades. PCR
      DGGE proved to be an effective tool in detecting non-culturable organisms present
      in these complex undefined cultures. In conclusion, while the culture-dependent
      identification methods or PCR-DGGE alone cannot comprehensively elucidate the
      bacterial species present in such complex cultures, their complementarity
      provides useful information on the identity of the constituents of NTCs and will
      aid in future development of defined probiotics. Moreover, for the purpose of
      analysing prototype NTCs during their development, PCR-DGGE overcomes the
      limitations associated with conventional culturing methods including their low
      sensitivities, inability to detect unculturable bacteria and unknown species,
      very slow turnabout time and poor reproducibility. This study demonstrated that
      PCR-DGGE is indeed more valuable in detecting predominant microbial populations
      between various NTCs than as an identification methodology, being more applicable
      as a quality control method used to analyse for batch-to-batch variation during
      NTC production.

PMID- 16814893
TI  - Technological characterization of a bacteriocin-producing Lactobacillus sakei and
      its use in fermented sausages production.
AB  - The aim of this paper was the technological characterization of a Lactobacillus
      sakei strain, able to produce the bacteriocin sakacin P, that was originally
      isolated from naturally fermented sausages. Experiments were conducted in situ,
      using MRS-based medium, and in situ, when the strain was inoculated as starter
      culture in real sausage fermentation. The results obtained underlined that the
      strain was able to grow in conditions that are commonly used in the production
      line, and only lactose and high concentrations of NaCl (5% w/v) reduced the
      capability for bacteriocin production. When inoculated in sausages, the strain
      showed a good performance, being able to colonize rapidly the ecosystem. A high
      number of isolates, capable of producing sakacin P, were already isolated after
      the third day of fermentation, and persisted throughout the course of the
      fermentation. The inoculated strain also affected other microbial colonization
      trends; in fact the total bacterial count and fecal enterococci showed a rapid
      decrease at the end of the fermentation. Moreover, during sensory evaluation, the
      final sausage product received high scores for the parameters of tenderness and
      juiciness, with medium acidity and low rancidity. Lastly, the panelists preferred
      the sausages produced with the L. sakei characterized in this study when compared
      to a fermented sausage produced with a commercial starter.

PMID- 16814894
TI  - Discovery, cloning and heterologous expression of secreted potato proteins reveal
      erroneous pre-mRNA splicing in Aspergillus oryzae.
AB  - A novel transposon assisted signal trapping (TAST) technology, developed to
      specifically select only the secreted proteins, was used to discover novel
      extracellular plant proteins from Solarium tuberosum infected with Phytophthora
      infestans. Analysis of 384 hits provided 191 P. infestans and S. tuberosum
      sequences of secreted proteins, with an approx. 2/3 of these originating from
      potato. Subsequent screening for interesting genes was carried out using
      bioinformatics. A selected variety of the discovered sequences are presented,
      including a novel S. tuberosum xyloglucan endotransglucosylase (StXTH), which was
      cloned and subjected to detailed heterologous expression studies in Aspergillus
      oryzae. RT-PCR analysis of mRNA from A. oryzae StXTH1 transformants revealed that
      parts of the mRNA pool had been incorrectly processed, and only weak and
      inconsistent indications of active protein could be detected. A high AT content
      of StXTH1 and the occurrence of A. oryzae intron donor, acceptor, and branch
      point recognition sites resulted in erroneous intron interpretation (cryptic
      introns) of parts of the mRNA coding sequence. This may explain the difficulties
      generally experienced in expressing plant genes in filamentous fungi.

PMID- 16814895
TI  - Location and phylogenetic analysis of the region immediately upstream of the
      granulin gene of the Clostera anachoreta granulovirus.
AB  - The region immediately upstream of the granulin gene from Clostera anachoreta
      granulovirus (ClanGV) was identified from hybridization experiments and
      sequenced. The sequence of 5122nt EcoRI restriction fragment was presented and
      compared with the equivalent area in other GVs. Database searches showed that
      this region contained three open reading frames (ORFs) similar to the baculovirus
      genes (egt, fgf and me53, respectively) and four ORFs unique to ClanGV genome.
      Phylogenetic trees of the baculovirus genes egt and me53 were constructed. These
      analyses indicated that ClanGV genes may be more closely related to CfGV, CpGV,
      ClGV, PoGV and AoGV than to PxGV and XcGV.

PMID- 16814896
TI  - Biodistribution characteristics of amino acid dendrimers and their PEGylated
      derivatives after intravenous administration.
AB  - In this study, we synthesized dendritic poly(L-lysine)s (DPKs), dendritic poly(L
      ornithine)s (DPOs), which are constructed as novel amino acid dendrimers, and
      PEGylated KG6 (the sixth generation of DPKs), and evaluated the physicochemical
      properties and biodistribution characteristics of these dendrimers. The particle
      size of DPKs and DPOs was well controlled in the nanometer range. The zeta
      potential of these dendrimers was slightly positive and this gradually increased
      in association with their generation. After intravenous administration to mice,
      all tested dendrimers cleared rapidly from blood flow and mainly accumulated in
      the liver and kidney. The hepatic and renal accumulation changed in a generation
      dependent manner. In contrast, no significant distributional differences between
      same generation of DPK and DPO were observed, although the constituent amino
      acids, particle size, and zeta-potential were different. However, PEGylation of
      KG6 caused great changes in particle size, zeta-potential, blood retention and
      organ distribution in vivo, indicating that the PEGylation is applicable strategy
      to improve biodistribution characteristics of dendrimeric molecules. The
      information provided by this study will be helpful for the development of future
      drug delivery systems using amino acid dendrimers as safe drug carriers.

PMID- 16814897
TI  - Under-utilization of capillary glucose monitoring by type 2 diabetic patients.
AB  - OBJECTIVES: Postprandial glycemic excursions contribute significantly to A1C
      level. Furthermore, postprandial plasma glucose (PPG) is an independent risk
      factor for cardiovascular disease. We have evaluated the frequency of monitoring
      and the level of PPG in type 2 diabetic patients followed by their family
      physician. PATIENTS AND METHODS: Canadian multicenter observational study,
      including 185 type 2 diabetic patients. Capillary blood glucose was measured with
      an Ultrasmart glucose meter (Life Scan) during a routine visit to their general
      practitioner. The patients also had to answer a questionnaire concerning the time
      since their last meal before the visit, and the frequency of postprandial
      monitorings defined as <or= 3h post-meal, as well as their current treatment.
      RESULTS: Twenty six percent of patients were treated with diet and exercise alone
      (Group 1; n=48), 58.4% with oral agents (Group 2; n=108), and 14% with insulin
      (Group 3; n=26); 1.6% did not know their treatment. The proportion of patients
      checking their PPG, at least once during the last 15 days was 16.7% (n=8) for
      Group 1, 37% (n=40) for Group 2 and 46.2% (n=12) for Group 3. The means (S.D.) of
      PPG were 8.7 mmol/L (3.5), 10.0 (3.7) and 12.7 (4.8) for Groups 1-3,
      respectively. Based on the Canadian Diabetes Association recommendations for PPG
      targets, only 36.2% had a good control (<8 mmol/L) while 41.6% had a poor control
      of their PPG (>10 mmol/L). A PPG >10 mmol/L was found in 18.8% (n=9), 43.5%
      (n=47) and 73.1% (n=19) of patients in Groups 1-3, respectively. Independent of
      treatment category, the mean (S.D.) PPG measured by capillary methods was above
      the recommended target: 10.6 mmol/L (3.7) <1-h postprandial; 10.0 mmol/L (4.2)
      between 1 and 2h postprandial meal; and 9.9 (3.9) 2 and 3h after meal.
      CONCLUSION: This observational study shows that a third of the patients measured
      their PPG and for those who did, only a third were within the recommended target.
      It suggests that the patients, and probably the treating physicians, are not
      aware of the importance of measuring PPG. Continued medical education strategies
      are required to implement the recommendations for measuring and treating PPG as
      part of the intensive treatment of diabetes.

PMID- 16814898
TI  - Effects of high glucose on cellular activity of periodontal ligament cells in
      vitro.
AB  - Periodontal ligament (PDL) cells are the most important cells in the healing of
      wounds and the regeneration of periodontal tissues. The response of PDL cells
      regarding cellular activity to high glucose concentration levels could be the key
      in understanding the events associated with the dental care of brittle diabetes.
      We studied the effect of high glucose concentration levels on the cellular
      activity of PDL cells from five non-diabetic patients in vitro. PDL cells were
      cultured for 14 days in a normal glucose medium (1100mg/l of glucose) or in a
      high glucose medium (4500mg/l of glucose) and a 3-(4,5-dimethylithiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assay for cellular viability was also
      performed. In order to evaluate the differentiation of PDL cells to osteoblast
      like cells, mineralized nodule formation was induced with supplemented media
      containing 50microg/ml of ascorbic acid, 10mM of beta-glycerophosphate and 100nM
      of dexamethasone for 21 days. High glucose significantly inhibited the
      proliferation of PDL cells and reduced the optic density of the MTT assay.
      Concerning the mineralized nodule formation, the percentage of the calcified area
      to the total culture dish of PDL cells in high glucose level was lower than that
      in the normal glucose medium. In conclusion, high glucose inhibits the
      proliferation and differentiation of PDL cells. The data provide an explanation
      for the delayed periodontal regeneration and healing in diabetic patients.

PMID- 16814899
TI  - Birth weight and type 1 diabetes among schoolchildren in Taiwan--A population
      based case-controlled study.
AB  - To explore the relationship between birth weight and type 1 diabetes, data from
      national birth registry and national surveillance of diabetes in Taiwanese
      schoolchildren were analyzed. From 1992 to 1997, all schoolchildren aged 6-18
      years were screened for diabetes by a mass urine survey program in Taiwan
      Province. This cohort consisted of 1966 children with diabetes and 1780 of
      randomly selected subjects with normal fasting glycemia. Questionnaires were
      designed for telephone interviews with students' parents or physicians to
      classify subjects' types of diabetes. The birth history of each participant was
      obtained from the Taiwan's Birth Registry. After merging the data, there were 835
      subjects, including 277 of type 1 diabetes and 533 of normal fasting glycemia
      available for the present analyses. The odds ratio (95% CI) for type 1 diabetes,
      after adjusting age, sex, socioeconomic status, family history of diabetes, birth
      order, breast-feeding, BMI, and gestational diabetes mellitus was 2.24 (1.11
      4.50) for children with low birth weight (<5th percentile, i.e., < or =2600 g)
      when compared with the referent group of a birth weight of 3000-3542 g
      (equivalent to the 25-75th percentile). In conclusion, low birth weight was
      associated with increased risk of type 1 diabetes in Taiwanese schoolchildren.

PMID- 16814900
TI  - Synthetic peptides derived from human antimicrobial peptide ubiquicidin
      accumulate at sites of infections and eradicate (multi-drug resistant)
      Staphylococcus aureus in mice.
AB  - The presence and antimicrobial activity of antimicrobial peptides (AMPs) has been
      widely recognized as an evolutionary preserved part of the innate immune system.
      Based on evidence in animal models and humans, AMPs are now positioned as novel
      anti-infective agents. The current study aimed to evaluate the potential
      antimicrobial activity of ubiquicidin and small synthetic fragments thereof
      towards methicillin resistant Staphylococcus aureus (MRSA), as a high priority
      target for novel antibiotics. In vitro killing of MRSA by synthetic peptides
      derived from the alpha-helix or beta-sheet domains of the human cationic peptide
      ubiquicidin (UBI 1-59), allowed selection of AMPs for possible treatment of MRSA
      infections. The strongest antibacterial activity was observed for the entire
      peptide UBI 1-59 and for synthetic fragments comprising amino acids 31-38. The
      availability, chemical synthesis opportunities, and size of these small peptides,
      combined with their strong antimicrobial activity towards MRSA make these
      compounds promising candidates for antimicrobial therapy and detection of
      infections in man.

PMID- 16814901
TI  - Intrathecal CART (55-102) attenuates hyperlagesia and allodynia in a mouse model
      of neuropathic but not inflammatory pain.
AB  - CART peptides are found in brain and spinal cord areas involved in pain
      transmission. In the present study, we investigated the role of rat CART (55-102)
      in the modulation of chronic pain using models of chronic neuropathic (nerve
      injury model) and inflammatory (carrageenan test) pain models in the mouse after
      intrathecal administration. The results show that CART (55-102) was highly
      effective in reversing the hyperalgesia and allodynia signs of chronic
      neuropathic pain in a dose-related manner at doses (0.05-2 microg/mouse) that did
      not affect motor coordination of the animals. These effects lasted for at least 3
      h after injection and were not blocked by naloxone, an opiate antagonist.
      Although CART (55-102) attenuated carrageenan-induced hyperalgesia, it failed to
      reduce the inflammation associated with this model. These results suggest the
      involvement of the CART peptides in the development of hyperalgesia and allodynia
      associated with neuropathic pain.

PMID- 16814902
TI  - Inhibition of allergen-induced airway inflammation and hyperreactivity by
      recombinant lactic-acid bacteria.
AB  - Recombinant lactic-acid bacteria (LAB) are able to inhibit allergen-specific T
      cell responses. In this study, we examined whether oral feeding of recombinant
      LAB was able to suppress allergen-induced airway inflammation and hyperreactivity
      (AHR) in a murine model. Animals were intraperitoneally sensitized with
      Dermatophagoides pteronyssinus group-5 allergen (Der p 5) and orally treated with
      recombinant LAB containing a plasmid-encoded Der p 5 gene or placebo on day 7 and
      day 14 for three days consecutively. Twenty-one days after sensitization, mice
      underwent inhalational challenging. Der p 5-specific immunological responses
      including changes to specific immunoglobulin G and E (IgE) levels, the presence
      of cells in the bronchoalveolar lavage fluid (BALF), and AHR were assessed
      following this inhalational challenge. We demonstrated that oral feeding of
      recombinant LAB could significantly decrease the synthesis of Der p 5-specific
      IgE, and AHR. Furthermore, following such treatment, we also noted that both
      neutrophils and eosinophils had infiltrated the BALF to a significantly lower
      extent, when compared to the vehicle-treated group. Neither recombinant allergen
      nor LAB alone was able to suppress allergen-induced immune responses. Our
      findings suggest that treatment with recombinant LAB at a low dose can suppress
      allergen-induced airway allergic inflammation, this providing a basis for
      developing a novel therapeutic method for allergic airway diseases.

PMID- 16814903
TI  - Protection against cutaneous leishmaniasis by intranasal vaccination with
      lipophosphoglycan.
AB  - We previously showed the opposing effect of systemic and mucosal vaccination with
      whole Leishmania amazonensis antigen (LaAg). Here, the role played by
      lipophosphoglycan (LPG) as the key disease-promoting component of intramuscular
      (i.m.) LaAg and its usefulness as a defined intranasal vaccine was investigated
      in murine cutaneous leishmaniasis. BALB/c mice were twice vaccinated by the i.m.
      route with 25mug of intact LaAg or with LaAg that was pretreated with anti-LPG
      3A1-La monoclonal antibody, prior to infection with L. amazonensis. LPG
      neutralization rendered the otherwise disease-promoting LaAg antigen protective,
      as observed by the smaller lesion sizes and reduced parasite burden. The
      increased resistance was accompanied by a markedly lower antigen-driven TGF-beta
      and IL-10 responses in the lesion-draining lymph nodes, concomitant with
      significantly higher IFN-gamma production. To test for intranasal efficacy, 10
      microg of affinity-purified LPG and its parental LaAg were twice instilled in the
      nostrils prior to L. amazonensis infection. In both cases, similarly slower
      lesion growth and lower parasite burden were found that was associated with
      increased IFN-gamma and IL-10 responses in the lesion-draining lymph nodes. These
      results support a role for LPG in the dual route-related effect of LaAg and shows
      its strong potential as a defined needle-free and adjuvant-free vaccine for
      cutaneous leishmaniasis.

PMID- 16814904
TI  - An emerging avian influenza A virus H5N7 is a genetic reassortant of highly
      pathogenic genes.
AB  - We full genome characterised the newly discovered avian influenza virus H5N7
      subtype combination isolated from a stock of Danish game ducks to investigate the
      composition of the genome and possible features of high pathogenicity. It was
      found that the haemagglutinin and the acidic polymerase genes were closely
      related to a low pathogenic H5 strain (A/Duck/Denmark/65047/04 H5N2). The
      neuraminidase and the non-structural genes were closely related to the highly
      pathogenic H7N7 strains from The Netherlands 2003. The basic polymerase genes 1
      and 2 were shared between the Danish H5N7 and H5N2 and the H7N7 from The
      Netherlands. The nucleoprotein and the matrix genes were closely related to H6
      strains. Thus, the new H5N7 subtype share genes with H5, H7 and H6 subtypes and
      possesses internal genes originating from highly pathogenic strains. The findings
      emphasize the need for surveillance presumed low pathogenic avian influenza A
      viruses.

PMID- 16814905
TI  - Resolution of diplopia after repair of the deep orbit.
AB  - The degree of resolution of diplopia after repair of a blow-out fracture of the
      orbital floor varies and depends on many factors. We present six patients, each
      of whom had extensive fractures of the floor of the orbit that extended
      posteriorly to its anatomical limit. The mean (range) time for the resolution of
      diplopia after reconstruction was 4.4 (1-7) months. We think that its slow
      resolution in these patients may require preoperative counselling, and also the
      postoperative management of patients with extensive disruptions of the floor of
      the orbit posterior to the anterior limit of the inferior orbital fissure (within
      the deep orbit) must be carefully planned.

PMID- 16814906
TI  - Transfer of a single flexor carpi ulnaris tendon for treatment of radial nerve
      palsy.
AB  - Between 1993 and 2002, 108 patients with isolated and persisting radial nerve
      palsy, underwent transfer of the flexor carpi ulnaris tendon alone to extensor
      digitorum communis, extensor indicis proprius and extensor pollicis longus. Only
      patients with sufficient flexor carpi ulnaris muscle power (grade M5) underwent
      this procedure. Long-term functional results were reviewed at a mean
      postoperative follow up of 48 (range 3-120) months. In comparison with the
      contralateral hand, the range of extension of the wrist was less but extension of
      the fingers and the MCP joints were similar to that of the normal hand. All
      patients improved functionally and could cope with their routine activities. Most
      were able to return to their previous jobs. There was no obvious difference in
      the end result of using this single transfer from our previous results using the
      three tendon transfers which are commonly used to treat radial nerve palsy. The
      single flexor carpi ulnaris tendon transfer has some advantages in terms of
      simplicity, shorter operation time, less morbidity and less surgical scars.

PMID- 16814907
TI  - Mycobacterium avium infection involving skin and soft tissue of the hand treated
      by radical debridement and reconstruction in addition to multidrug chemotherapy.

PMID- 16814908
TI  - An MRI evaluation of carpal tunnel dimensions in healthy wrists: Implications for
      carpal tunnel syndrome.
AB  - BACKGROUND: Deviated wrist postures and pinch grip use have been linked to the
      development of carpal tunnel syndrome and are likely related to the size and
      shape of the carpal tunnel. The purpose of this study was to quantify carpal
      tunnel dimensions with changes in wrist posture and pinch grip. METHODS: Eight
      healthy volunteers (4 male, 4 female) underwent magnetic resonance imaging of
      their dominant wrists under seven conditions which included: 30 degrees wrist
      extension, neutral and 30 degrees flexion (with and without a 10 N pinch force)
      and a fist with a neutral wrist. Cross-sectional area of the carpal tunnel and
      its contents were calculated at 3mm increments along the length of the tunnel and
      integrated to calculate volumes. Ratios were calculated between the contents of
      the tunnel to the tunnel itself for area and volume. FINDINGS: The use of a
      correction factor significantly reduced volume and distal carpal tunnel area in
      flexed and extended wrists. Carpal tunnel areas were largest in neutral and
      smallest at the distal end with wrist flexion. An extended wrist resulted in the
      smallest carpal tunnel and content volumes as well as the smallest carpal tunnel
      content volume to carpal tunnel volume ratios. While men had significantly larger
      areas and volumes than women for both the carpal tunnel and it contents, there
      were no differences in ratios between the contents and tunnel size.
      INTERPRETATION: A simple correction factor for non-perpendicular magnetic
      resonance images proved useful in relating volume changes to known pressure
      changes within the carpal tunnel. More inclusive and detailed evaluation of the
      carpal tunnel and its contents is required to fully understand mechanisms for
      median nerve compression in the carpal tunnel.

PMID- 16814909
TI  - Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in
      pathophysiology, diagnosis and treatment.
AB  - Although cobalamin (vitamin B12) was isolated almost 60 years ago, its
      biochemical, physiologic and neurologic effects remain incompletely defined. New
      observations suggest renal regulation of cobalamin metabolism; actions of
      cobalamin on nucleic acid and protein function; and a role for cobalamin in
      cytokine and growth factor regulation. Clinically, no gold standard has emerged
      for the diagnosis of cobalamin deficiency. Moreover, cobalamin resistance may
      occur in diabetes, renal insufficiency and advanced age, leading to functional
      cobalamin deficiency despite adequate cobalamin nutriture. Finally, high-dose
      cobalamin therapy may have salutary pharmacologic effects on neurologic function
      in a variety of disorders. Many studies lacked appropriate control groups.
      However, at this time, therapeutic trials with pharmacologic doses of cobalamin
      are suggested when findings consistent with cobalamin deficiency are present
      regardless of the results of diagnostic tests. While oral cobalamin immediate
      release is adequate for many patients, its effectiveness in reversing neurologic
      abnormalities has yet to be established.

PMID- 16814910
TI  - Heavy metal accumulation and metallothionein concentration in the frog Rana
      ridibunda after exposure to chromium or a mixture of chromium and cadmium.
AB  - The accumulation of two heavy metals (chromium (Cr) and cadmium (Cd)) in the
      liver, kidney and gut of Rana ridibunda exposed to Cr or to a mixture of Cr and
      Cd was investigated. The concentration of metallothioneins (MTs) in the same
      tissues was also studied. Both metals accumulated mainly in the kidney. Cr
      accumulation in the liver and gut was not affected by the presence of Cd.
      Furthermore, Cr concentration in the kidney was doubled when Cd was present. MT
      concentration did not increase after Cr treatment but it increased two- to six
      fold over control values in mixture-exposed frogs, the highest value being
      observed in the gut. MTs in the gut could act as a barrier preventing ingested
      heavy metals from entering the blood stream. MT concentration correlated
      positively with Cd concentrations in both the liver and the gut of mixture
      exposed animals.

PMID- 16814911
TI  - The health effects of chrysotile: current perspective based upon recent data.
AB  - This review substantiates kinetically and pathologically the differences between
      chrysotile and amphiboles. The serpentine chrysotile is a thin walled sheet
      silicate while the amphiboles are double-chain silicates. These different
      chemistries result in chrysotile clearing very rapidly from the lung (T(1/2)=0.3
      to 11 days) while amphiboles are among the slowest clearing fibers known
      (T(1/2)=500 days to infinity). Across the range of mineral fiber solubilities
      chrysotile lies towards the soluble end of the scale. Chronic inhalation toxicity
      studies with chrysotile in animals have unfortunately been performed at very high
      exposure concentrations resulting in lung overload. Consequently their relevance
      to human exposures is extremely limited. Chrysotile following subchronic
      inhalation at a mean exposure of 76 fibers L>20 microm/cm(3) (3413 total
      fibers/cm(3)) resulted in no fibrosis (Wagner score 1.8-2.6), at any time point
      and no difference with controls in BrdU response or biochemical and cellular
      parameters. The long chrysotile fibers were observed to break apart into small
      particles and smaller fibers. Toxicologically, chrysotile which rapidly falls
      apart in the lung behaves more like non-fibrous mineral dusts while response to
      amphibole asbestos reflects its insoluble fibrous structure. Recent quantitative
      reviews of epidemiological studies of mineral fibers have determined the potency
      of chrysotile and amphibole asbestos for causing lung cancer and mesothelioma in
      relation to fiber type have also differentiated between these two minerals. The
      most recent analyses also concluded that it is the longer, thinner fibers that
      have the greatest potency as has been reported in animal inhalation toxicology
      studies. However, one of the major difficulties in interpreting these studies is
      that the original exposure estimates rarely differentiated between chrysotile and
      amphiboles. Not unlike some other respirable particulates, to which humans are,
      or have been heavily occupationally exposed, there is evidence that heavy and
      prolonged exposure to chrysotile can produce lung cancer. The value of the
      present and other similar studies is that they show that low exposures to pure
      chrysotile do not present a detectable risk to health. Since total dose over time
      decides the likelihood of disease occurrence and progression, they also suggest
      that the risk of an adverse outcome may be low if even any high exposures
      experienced were of short duration.

PMID- 16814913
TI  - Effectiveness of customary use of phytosterol/-stanol enriched margarines on
      blood cholesterol lowering.
AB  - Postlaunch monitoring of functional foods can encompass monitoring of
      effectiveness under conditions of customary use. To this end, the effectiveness
      of phytosterol/-stanol enriched margarine consumption in free-living conditions
      was investigated with data from the Dutch "Doetinchem cohort study". In total,
      4,505 subjects (aged 26-70 years) were examined in 1994-1998 and re-examined
      during 1999-2003. A general and a food frequency questionnaire and non-fasting
      blood samples for total and HDL cholesterol determination were obtained. Subjects
      were stratified into phytosterol/-stanol enriched margarine users (n = 84) and
      non-users (n = 4,421) based on the re-examination data, as these margarines were
      available on the Dutch market from 1999 onwards. Mean spontaneous daily use (g +/
      SD) of phytosterol-containing margarine (n = 71) was 15 +/- 8 and of phytostanol
      containing margarine (n = 13) 9+/-6. After five years, total blood cholesterol
      had increased with 0.26 mmol/l in non-users while it had not significantly
      changed in users. The difference in total blood cholesterol change in users
      versus non-users was -0.30 mmol/l (p < 0.001). The beneficial effect of the
      phytosterol/-stanol enriched margarine, used under customary conditions can be
      characterized as a stabilization of cholesterol levels. This is the first report
      finding a modest beneficial effect on blood cholesterol level under customary
      conditions thereby partly confirming findings from clinical trials.

PMID- 16814912
TI  - The promises and limitations of female-initiated methods of HIV/STI protection.
AB  - New methods are now available, and others are being developed, that could enable
      women to take the initiative in preventing sexually transmitted infections.
      However, attempts to capitalize on "female-controlled" preventive methods thus
      far have met with limited success. Female-initiated methods were introduced to
      intervene in the state of gender relations and assist women who are disempowered
      vis-a-vis their male partners. Paradoxically, however, we underscore that it is
      the very structure of regional and local gender relations that shapes the
      acceptability (or lack of acceptability) of these methods. This paper
      specifically addresses how the structure of gender relations-for better and for
      worse-shapes the promises and limitations of widespread use and acceptance of
      female-initiated methods. We draw on examples from around the world to underscore
      how the regional specificities of gender (in)equality shape the acceptance,
      negotiation, and use of these methods. Simultaneously, we demonstrate how the
      introduction and sustained use of methods are shaped by gender relations and
      offer possibilities for reinforcing or challenging their current state. Based on
      our analyses, we offer key policy and programmatic recommendations to increase
      promotion and effective use of women-initiated HIV/STI protection methods for
      both women and men.

PMID- 16814914
TI  - Genotoxicity associated to exposure to Prestige oil during autopsies and cleaning
      of oil-contaminated birds.
AB  - After the accident involving the oil tanker Prestige in November 2002 near 63,000
      tons of heavy oil reached Galician coast (Northwest of Spain). This unleashed a
      large movement of volunteers to collaborate in several cleaning tasks. The aim of
      this study was to determine whether handling of Prestige oil-contaminated birds
      during autopsies and cleaning may have resulted in genotoxic damage. We have also
      evaluated the possible influence of DNA repair genetic polymorphisms (XRCC1
      codons 194 and 399, XRCC3 codon 241 and APE1 codon 148) on susceptibility to the
      genotoxic effects evaluated. Exposure levels were analysed by determining
      volatile organic compounds in air samples. Peripheral blood samples were obtained
      from 34 exposed and 35 controls, and comet assay and micronucleus (MN) test were
      carried out. Genotyping was performed following PCR-RFLP procedures. Results
      obtained have shown significantly higher DNA damage, but not cytogenetic damage,
      in exposed individuals than in controls, related to time of exposure. Among
      exposed individuals, carriers of the variant alleles XRCC1 399Gln and APE1 148Glu
      have shown altered DNA damage with regard to wild-type homozygotes, suggesting
      exposure-genotype interactions. No effect of the DNA repair genetic polymorphisms
      analysed was observed in the MN test.

PMID- 16814915
TI  - Curcumin attenuates gentamicin-induced renal oxidative damage in rats.
AB  - The present investigation reports the effect of curcumin, an antioxidant, on
      gentamicin-induced-renal oxidative damage in rats. Curcumin (200 mg/kg p.o.) was
      administered for 2 weeks before and 1 week simultaneously with gentamicin (100
      mg/kg i.p.). Saline treated rats served as control. Serum creatinine, blood urea
      (BUN), urinary protein, glucose, urine gamma glutamyl transferase and urine
      volume increased in rats treated with gentamicin while creatinine clearance
      decreased compared to controls P<0.001. Renal histological examination revealed
      tubular necrosis. Curcumin significantly normalized the above parameters.
      Gentamicin decreased the activities of catalase (CAT), gutathione peroxidase
      (GSHPx) and the level of glutathione (GSH) but the activity of copper, zinc
      superoxide dismutase (Cu, Zn-SOD) was unaltered compared to control. Curcumin
      attenuated the gentamicin-induced reduction in the activities of CAT, GSHPx and
      level of GSH by 31%, 55% and 74%, respectively. Curcumin attenuated the
      gentamicin-induced increases in both plasma malondialdehyde (MDA) and kidney MDA
      by 57% and 62%, respectively, as well as lipid hydroperoxide (LOOH) formation by
      52% and 56% in rat plasma and kidney, respectively. However, Curcumin did not
      reduce gentamicin-induced formation of LOOH, both in the plasma and kidney, in
      the presence of exogenous oxidants (1 mM FeSO4, 1 mM ascorbate, 0.2 mM H2O2). Our
      data indicate that the natural antioxidant curcumin can be a potent protective
      agent against renal oxidative damage mediated by gentamicin.

PMID- 16814916
TI  - Utility of the mouse dermal promotion assay in comparing the tumorigenic
      potential of cigarette mainstream smoke.
AB  - The International Agency for Research on Cancer (IARC) has classified a number of
      the chemical constituents reported in cigarette mainstream smoke (MS) as
      carcinogens. In the international literature, 81 IARC classified carcinogens have
      been reported historically in MS. Cigarette smoke is a complex aerosol of minute
      liquid droplets (termed the particulate phase) suspended within a mixture of
      gases (CO(2), CO, NO(x), etc.) and semi-volatile compounds. The gases and semi
      volatiles are termed the vapor phase. Due to early difficulties in inducing
      carcinomas in laboratory animals following inhalation exposure to MS, the mouse
      dermal promotion assay became the standard method of comparing the tumorigenic
      potential of cigarette smoke condensates (the particulate phase of MS nearly
      devoid of MS gases and having a significant reduction of the semi-volatile
      components of the vapor phase). Of the 81 IARC carcinogens reported in MS, 48 are
      found exclusively in the particulate phase, 29 in the vapor phase only, and four
      IARC carcinogens in both phases. A general comparison of the quantity and potency
      of the individual carcinogenic constituents of the MS vapor and particulate
      phases illustrates that the potential carcinogenic contribution from the vapor
      phase might be significant. Therefore, the mouse dermal promotion assay may not
      be a sensitive comparator of the tumorigenic potential of different MSs
      displaying a diversity of vapor phase components. However, when used in a weight
      of-the-evidence approach that includes smoke chemistry, in vitro studies using
      whole smoke and human exposure studies evaluating both vapor and particulate
      phase smoke constituents, the mouse dermal promotion assay remains an important
      risk assessment tool as the only test that reproducibly measures the tumorigenic
      potential of cigarette smoke condensate.

PMID- 16814917
TI  - Cadmium toxicity in animal cells by interference with essential metals.
AB  - Cadmium is found in the environment as part of several, mainly zinc-rich, ores.
      It has been used in many technological applications, but biological systems
      generally failed to safely deal with this element. In mammalian biology, cadmium
      exposure jeopardizes health and mechanisms of cadmium toxicity are multifarious.
      Mainly because bioavailable cadmium mimics other metals that are essential to
      diverse biological functions, cadmium follows a Trojan horse strategy to get
      assimilated. Metals susceptible to cadmium deceit include calcium, zinc, and
      iron. The wealth of data addressing cadmium toxicity in animal cells is briefly
      reviewed with special emphasis on disturbance of the homeostasis of calcium,
      zinc, and iron. A limited number of tissues and cell types are considered as main
      targets for cadmium toxicity. Still, the diversity of pathways affected by
      cadmium exposure points to a more general threat to basic cellular functions. The
      poor efficiency of cellular export systems for cadmium explains the long
      residence time of the element in mammals. Therefore, proper disposal and educated
      uses of this technologically appealing, but biologically malicious, element
      should be favored in the future. The comprehensive knowledge of cadmium
      biological effects is indeed a necessary step to protect human and animal
      populations from environmental and anthropological exposures.

PMID- 16814918
TI  - Role of the yeast ABC transporter Yor1p in cadmium detoxification.
AB  - Growth of yeast strains, either deleted for the vacuolar ABC transporter Ycf1 or
      deleted for the plasma membrane ABC transporter Yor1p or overexpressing Yor1p,
      were compared for their sensitivity to cadmium. On solid medium cell death (or
      growth inhibition) was observed at cadmium concentrations higher than 100 microM
      when yeasts were grown at 30 degrees C for 24 h. However, for all tested strains
      cell death (or growth inhibition) was already observed at 40 microM cadmium when
      incubated at 23 degrees C for 60 h. Thus cadmium is more toxic to yeast at 23
      degrees C than at 30 degrees C. At 23 degrees C, the Deltayor1 strain grew more
      slowly than the wild-type strain and the double Deltayor1, Deltaycf1 deleted
      strain was much more sensitive to cadmium than each single Deltayor1 or Deltaycf1
      deletant. Overexpression of Yor1p in a Deltaycf1 strain restores full growth.
      Cadmium uptake measurements show that Deltaycf1 yeast strains expressing or
      overexpressing Yor1p store less cadmium than the corresponding Deltaycf1,
      Deltayor1 strain. The strains expressing Yor1p display an energy-dependent efflux
      of cadmium estimated for the yeast overexpressing Yor1p to be about 0.02 nmol
      109Cd/mg protein/min. Yeast cells loaded with radiolabeled glutathione and then
      with radioactive cadmium displayed a twice-higher efflux of glutathione than that
      of cadmium suggesting that Yor1p transports both compounds as a bis-glutathionato
      cadmium complex. All together, these results suggest that in addition to being
      accumulated in the yeast vacuole by Ycf1p, cadmium is also effluxed out of the
      cell by Yor1p.

PMID- 16814919
TI  - Effects of oxidative modifications induced by the glycation of bovine serum
      albumin on its structure and on cultured adipose cells.
AB  - Non-enzymatic glycosylation (glycation) and oxidative damages represent major
      research areas insofar as such modifications of proteins are frequently observed
      in numerous states of disease. Albumin undergoes structural and functional
      alterations, caused by increased glycosylation during non insulin-dependent
      diabetes mellitus, which is closely linked with the early occurrence of vascular
      complications. In this work, we first characterized structural modifications
      induced by the glycation of bovine serum albumin (BSA). A pathophysiological
      effect of glycated BSA was identified in primary cultures of human adipocytes as
      it induces an accumulation of oxidatively modified proteins in these cells. BSA
      was incubated in the presence or absence of physiological, pathological or supra
      physiological concentrations of glucose at 37 degrees C for 7 weeks. Enhanced BSA
      glycation percentages were determined using boronate affinity columns. The
      occurrence of oxidative modifications was found to be enhanced in glycated BSA,
      after determination of the free thiol groups content, electrophoretic migration
      and infrared spectrometry spectra. An accumulation of carbonyl-modified proteins
      and an increased release of isoprostane were observed in cell media following the
      exposure of adipocytes to glycated albumin. These results provide a new possible
      mechanism for enhanced oxidative damages in diabetes.

PMID- 16814920
TI  - Hydrogen peroxide producing lactobacilli in women with vaginal infections.
AB  - OBJECTIVE: Hydrogen peroxide producing lactobacilli are isolated from the vaginas
      of a majority of healthy reproductive age women. Their toxic and inhibitory
      effect against the overgrowth of pathogens in the vagina is documented by in
      vitro studies. Clinical studies concerning the role of hydrogen peroxide
      producing lactobacilli in vaginal infections are controversial. STUDY DESIGN: The
      aim of this study was to isolate lactobacilli from women with major vaginal
      infections: bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and
      trichomoniasis (TV), and from women with normal flora (NF), to test their ability
      to produce hydrogen peroxide, to quantitate lactobacilli and to evaluate factors
      related to the colonization of vagina with hydrogen peroxide producing
      lactobacilli. The study group comprised 108 women: 27 with VVC, 26 with BV, 20
      with TV and 35 with NF. Data was analysed with Fisher exact test, chi2-test, and
      ANOVA. RESULTS: Lactobacilli were isolated from 81.5% of women with VVC, 58% of
      women with BV (p=0019), 55% of women with TV (p=0.015) and from 86% of women with
      NF. The majority of isolates of lactobacilli from women with VVC, TV and NF
      produced hydrogen peroxide (77%, 63.5% and 80%, respectively), compared with
      women with BV where only 26.5% of isolates produced hydrogen peroxide (p=0.01).
      Quantitative analysis showed that in an overwhelming majority of women colonized
      with lactobacilli, their count was >10(7) CFU/ml. Upon evaluation of behavioural
      and demographic characteristics, we found that smokers had a lower incidence of
      isolation of hydrogen peroxide producing lactobacilli (p=0.018). Our results
      showed that women with BV lack lactobacilli, especially hydrogen peroxide
      producing ones. Women with TV had a lower rate of lactobacilli. In women with
      VVC, there was neither significant difference in the isolation of lactobacilli,
      nor in their ability to produce hydrogen peroxide, compared to women with NF.
      CONCLUSION: Our results point out that hydrogen peroxide producing lactobacilli
      could protect against the development of BV, but not against VVC and TV.

PMID- 16814921
TI  - Thermodynamics of proteins in unusual environments.
AB  - Some aspects of protein thermodynamics in unconventional environments are
      addressed and discussed. Aqueous medium, especially dilute solution is the
      'usual' ambient, which mediates all the interactions between protein and nearby
      molecules. When the water content is low, the surroundings may be considered
      'unusual', exerting new stresses on the protein molecule and demanding different
      responses and property changes. The unusual systems considered in this article
      are low-water protein environments, including nearly dry state powders, organic
      solvent dispersions and reverse micelles' inclusions. The changes of hydration
      experienced by the protein after immobilization on solid supports are emphasized
      with respect to the free bulk solution state. Finally, the aqueous medium altered
      by water connectivity perturbing agents (polysaccharides) or in macromolecular
      crowding conditions (in the presence of polyols) is also considered as highly not
      ideal protein environments. The different responses elicited by the protein under
      the stress induced by drastic surrounding alterations may give insights for the
      controlled exploitation of the protein's biological and thermodynamic properties.

PMID- 16814922
TI  - Potential of cadmium sulphide nanorods as an optical microscopic probe to the
      folding state of cytochrome C.
AB  - The folding behavior of cytochrome C (Cyt-C) conjugated with CdS nanorods (CdSnr)
      is amenable to monitoring by bright field microscopy, the porosity and
      percolating behavior of such protein conjugated nanoclusters depending on the
      folding history prior to the conjugation. The method has been used to predict the
      thermal melting behavior as well as guanidine hydrochloride induced unfolding of
      Cyt-C. Dynamic light scattering studies indicate that the size distribution of
      the nanoforms widens in presence of the protein. Furthermore, there is emergence
      of clusters with higher conductivity and altered zeta potential. Increase of
      second virial coefficient of CdS nanoforms in the presence of Cyt-C (obtained
      from static light scattering experiments) implies presence of protein coat over
      the hydrophobic nanosurface. The results are supported by morphological changes
      observed through scanning electron microscopy (SEM). Accordingly, the X-ray
      diffraction pattern shows a change of crystallographic orientations of CdSnr in
      presence of Cyt-C.

PMID- 16814923
TI  - Para-chlorophenol containing synthetic wastewater treatment in an activated
      sludge unit: effects of hydraulic residence time.
AB  - Due to the toxic nature of chlorophenol compounds present in some chemical
      industry effluents, biological treatment of such wastewaters is usually realized
      with low treatment efficiencies. Para-chlorophenol (4-chlorophenol, 4-CP)
      containing synthetic wastewater was treated in an activated sludge unit at
      different hydraulic residence times (HRT) varying between 5 and 30 h while the
      feed COD (2500 mg l(-1)), 4-CP (500 mg l(-1)) and sludge age (SRT, 10 days) were
      constant. Effects of HRT variations on COD, 4-CP, toxicity removals and on
      settling characteristics of the sludge were investigated. Percent COD removals
      increased and the effluent COD concentrations decreased when HRT increased from 5
      to 15 h and remained almost constant for larger HRT levels. Nearly, 91% COD and
      99% 4-CP removals were obtained at HRT levels above 15 h. Because of the highly
      concentrated microbial population at HRT levels of above 15 h, low effluent
      (reactor) 4-CP concentrations and almost complete toxicity removals were
      obtained. High biomass concentrations obtained at HRT levels above 15 h were due
      to low 4-CP contents in the aeration tank yielding negligible inhibition effects
      and low maintenance requirements. The sludge volume index (SVI) decreased with
      increasing HRT up to 15 h due to high biomass concentrations at high HRT levels
      resulting in well settling sludge with low SVI values. Hydraulic residence times
      above 15 h resulted in more than 90% COD and complete 4-CP and toxicity removals
      along with well settling sludge.

PMID- 16814924
TI  - Industrial sustainability in China: practice and prospects for eco-industrial
      development.
AB  - China is a large densely populated country undergoing rapid industrialization and
      is becoming one of the world's biggest consumers of natural resources. This
      circumstance provides a sharp contrast with other countries. As China is so
      significant in the global economy, studies of its eco-industrial development are
      very important. In this study we examined the state of eco-industrial development
      in China and have drawn conclusions from this analysis about some of the future
      prospects for sustainable development. In the analysis, we investigated the
      application of industrial ecology concepts by reference to several case studies.
      We have therefore described the current environmental situation in China, and
      have provided an overview of eco-industrial development and its implementation.
      Constraints to industrial sustainability in China have also been examined. We
      consider that eco-industrial development in China is in its infancy, and that
      closed loops involving chains and industrial symbiotic webs are the technological
      key and core of successful initiatives in the application of industrial ecology.
      In the case studies, we found that each system has different characteristics and
      management concerns. Our major conclusion is that even though China's Agenda 21
      highlights the principles and sets the directions for eco-industrial development,
      these have not yet become essential ingredients in the country's industrial
      policy and practice for implementing Agenda 21.

PMID- 16814925
TI  - Random biopsies in bladder tumors: in most cases, you shall not!

PMID- 16814926
TI  - Application of paclitaxel-eluting metal mesh stents within the pig ureter: an
      experimental study.
AB  - OBJECTIVE: The purpose of the present study is to compare the standard bare metal
      stents (BMS) with the Paclitaxel-Drug Eluting Stent (DES) in the ureter of a pig
      model. MATERIALS AND METHODS: We report on an experimental study with ten female
      pigs weighing between 25 and 30 kg. The stents were randomly placed in either the
      right or left ureter in each of 10 study animals, for a total of 20 stented
      ureters. Ten ureters were stented with an R-Stent (Orbus Medical Technologies,
      Hoevelaken Netherlands), and ten with a Paclitaxel-Eluting Coronary Stent (Boston
      Scientific, Natick, MA, USA). Patency was measured by radiograph of the
      nephrostomy tract, intravenous urography and virtual endoscopy at 24 hours and 21
      days after the initial procedure, respectively. RESULTS: Free flow of urine
      through the stents into the bladder was documented in all stented ureters 24
      hours after stent insertion by radiograph of the nephrostomy tract. At the 21 day
      follow-up examination, 5 R-Stents were found to be completely occluded and two
      partially stenosed, whereas no occluded stent was detected in the Paclitaxel-DES
      group. Pathology examination of the stents at 21 days follow-up showed that the
      obstructed R-Stents generated severe inflammation with metaplasia of the
      urothelium. The Paclitaxel-Eluting MS generated a mild inflammatory response
      within the ureteral lumen at the site of the stent, without hindering ureteral
      patency. R-stents proved to develop more hyperplasia compared to the Paclitaxel
      Eluting MS. CONCLUSIONS: Paclitaxel-DES, when compared with the standard R- Stent
      BMS, generated less inflammation and/or hyperplasia of the surrounding tissues,
      thus maintaining ureteral patency. Long-term animal trials are required to
      further validate our results.

PMID- 16814927
TI  - Diagnostic value of MRI in a pelvic mass of prostatic origin.
AB  - We report on the case of a 55-year-old male with acute urinary retention, caused
      by a large pelvic mass. Contrast enhanced computed tomography showed a
      vascularized prostatic mass with calcifications. To rule out potential bladder
      and rectum infiltration and to optimize imaging prior to surgical exploration, an
      MRI examination including MR angiography and spectroscopy was performed. Clinical
      findings including intraoperative results are presented in this report in detail
      and correlated to the results of the state of the art magnetic resonance imaging.

PMID- 16814928
TI  - Goat warble fly infestation in Jordan.

PMID- 16814929
TI  - Structural analysis and classification of native proteins from E. coli commonly
      co-purified by immobilised metal affinity chromatography.
AB  - Immobilised metal affinity chromatography (IMAC) is the most widely used
      technique for single-step purification of recombinant proteins. However, despite
      its use in the purification of heterologue proteins in the eubacteria Escherichia
      coli for decades, the presence of native E. coli proteins that exhibit a high
      affinity for divalent cations such as nickel, cobalt or copper has remained
      problematic. This is of particular relevance when recombinant molecules are not
      expressed at high levels or when their overexpression induces that of native
      bacterial proteins due to pleiotropism and/or in response to stress conditions.
      Identification of such contaminating proteins is clearly relevant to those
      involved in the purification of histidine-tagged proteins either at small/medium
      scale or in high-throughput processes. The work presented here reviews the native
      proteins from E. coli most commonly co-purified by IMAC, including Fur, Crp,
      ArgE, SlyD, GlmS, GlgA, ODO1, ODO2, YadF and YfbG. The binding of these proteins
      to metal-chelating resins can mostly be explained by their native metal-binding
      functions or their possession of surface clusters of histidine residues. However,
      some proteins fall outside these categories, implying that a further class of
      interactions may account for their ability to co-purify with histidine-tagged
      proteins. We propose a classification of these E. coli native proteins based on
      their physicochemical, structural and functional properties.

PMID- 16814930
TI  - Clozapine reverses increased brown adipose tissue thermogenesis induced by 3,4
      methylenedioxymethamphetamine and by cold exposure in conscious rats.
AB  - Clozapine, an atypical antipsychotic agent important for the treatment of
      schizophrenia, has marked inhibitory effects on sympathetic outflow to the
      thermoregulatory cutaneous circulation. In rabbits clozapine reverses ear pinna
      vasoconstriction induced either by administration of MDMA (3,4
      methylenedioxymethamphetamine, ecstasy) or by exposing the animal to a cold
      environment. In rats, both these procedures are known to increase sympathetic
      activation of interscapular brown adipose tissue (iBAT) thermogenesis, important
      for heat production in the rat. In the present study in conscious rats we
      determined whether clozapine reduces iBAT thermogenesis induced by MDMA and by
      exposure to cold. We designed our study so that we could also determine effects
      of clozapine on the acute (stress-induced) increases in iBAT thermogenesis
      initiated by the process of s.c. injection. MDMA increased iBAT temperature
      (+1.7+/-0.2 degrees C after 90 min, P<0.01, n=14 measurements from seven rats
      each studied on two occasions). Clozapine acutely reversed the MDMA-elicited
      increase in iBAT temperature (-1.3+/-0.2 degrees C 60 min after clozapine
      treatment following MDMA versus +0.3+/-0.2 degrees C for 60 min after vehicle
      treatment following MDMA, P<0.01, n=7). Clozapine also reduced stress-induced
      increases in iBAT temperature, as well as increases elicited by exposing rats to
      a cold (5 degrees C) environment. Results, taken together with our previous
      findings, suggest that MDMA activates the sympathetic thermoregulatory outputs
      (including the output to iBAT) that defend body temperature against cold exposure
      and that increase body temperature in response to environmental stress.
      Clozapine's marked inhibition of iBAT thermogenesis may provide a clue to its
      marked tendency to cause obesity when used to treat humans with mental disorders
      including schizophrenia. Our demonstration in rats that clozapine decreases
      sympathetically-mediated increases in iBAT temperature elicited by MDMA adds to
      the likelihood that clozapine and clozapine-like agents might be therapeutically
      effective in life threatening hyperthermia induced by MDMA in humans.

PMID- 16814931
TI  - Neurotensin selectively facilitates glutamatergic transmission in globus
      pallidus.
AB  - The tridecapeptide neurotensin has been demonstrated to modulate
      neurotransmission in a number of brain regions. There is evidence that
      neurotensin receptors exist in globus pallidus presynaptically and
      postsynaptically. Whole-cell patch-clamp recordings were used to investigate the
      modulatory effects of neurotensin on glutamate and GABA transmission in this
      basal ganglia nucleus in rats. Neurotensin at 1 microM significantly increased
      the frequency of glutamate receptor-mediated miniature excitatory postsynaptic
      currents. In contrast, neurotensin had no effect on GABA(A) receptor-mediated
      miniature inhibitory postsynaptic currents. The presynaptic facilitation of
      neurotensin on glutamatergic transmission could be mimicked by the C-terminal
      fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1
      8). The selective neurotensin type-1 receptor antagonist, SR48692 {2-[(1-(7
      chloro-4-quinolinyl)-5-2(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino]
      tricyclo(3.3.1.1.(3.7))-decan-2-carboxylic acid}, blocked this facilitatory
      effect of neurotensin, and which itself had no effect on miniature excitatory
      postsynaptic currents. The specific phospholipase C inhibitor, U73122 {1-[6
      [[17beta-3-methoyyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione},
      significantly inhibit neurotensin-induced facilitation on glutamate release.
      Taken together with the reported postsynaptic depolarization of neurotensin in
      globus pallidus, it is suggested that neurotensin excites the globus pallidus
      neurons by multiple mechanisms which may provide a rationale for further
      investigations into its involvement in motor disorders originating from the basal
      ganglia.

PMID- 16814932
TI  - Estrogen-induced region specific decrease in the density of 5-bromo-2
      deoxyuridine-labeled cells in the olfactory bulb of adult female rats.
AB  - Effects of chronic estrogen treatment on the survival rate of newly integrated
      interneurons were studied in the olfactory bulb of adult (250-300 g) female rats.
      Ovariectomized rats received 17-beta estradiol dissolved in sesame oil (i.p., 100
      microg/100 g body weight [b.w.]) during six consecutive days, and on day 6 they
      were also injected with the mitotic marker 5-bromo-2-deoxyuridine (BrdU, i.p., 50
      mg/kg b.w.) in every 2 hours during 8 hours. After 21 days of survival animals
      were killed and the density of BrdU-immunoreactive cells was analyzed in the
      granule cell and glomerular layer both in the main and accessory olfactory bulb.
      A significant decrease was found in the density of BrdU-labeled cells in both
      layers examined in the accessory olfactory bulb of ovariectomized and estradiol
      treated rats when compared with those of ovariectomized and vehicle-treated
      animals. In the main olfactory bulb, in contrast, no difference was observed in
      the density of BrdU-immunoreactive cells in either of the two layers. Our results
      suggest that cells destined to the glomerular and granule cell layers react in
      the same way to chronic estrogen treatment, and the effect of estradiol is region
      specific, at least, within the olfactory bulb. 17-Beta estradiol reduces the
      density of newly generated cells in the accessory olfactory bulb, an area
      involved in the perception of pheromones, thus having a role in regulating sexual
      behavior, while the rate of integration and survival of newly born cells in the
      first relay station of the main olfactory pathway, i.e. the main olfactory bulb,
      remains unchanged.

PMID- 16814933
TI  - Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated
      protein-2 immunoreactivity in learned helplessness rats and antidepressant
      treated rats.
AB  - Learned helplessness rats are thought to be an animal model of depression. To
      study the role of synapse plasticity in depression, we examined the effects of
      learned helplessness and antidepressant treatments on synapsin I (a marker of
      presynaptic terminals), growth-associated protein-43 (GAP-43; a marker of growth
      cones), and microtubule-associated protein-2 (MAP-2; a marker of dendrites) in
      the hippocampus by immunolabeling. (1) Learned helplessness rats showed
      significant increases in the expression of synapsin I two days after the
      attainment of learned helplessness, and significant decreases in the protein
      expression eight days after the achievement of learned helplessness. Subchronic
      treatment of naive rats with imipramine or fluvoxamine significantly decreased
      the expression of synapsin I. (2) Learned helplessness increased the expression
      of GAP-43 two days and eight days after learned helplessness training. Subchronic
      treatment of naive rats with fluvoxamine but not imipramine showed a tendency to
      decrease the expression of synapsin I. (3) Learned helplessness rats showed
      increased expression of MAP-2 eight days after the attainment of learned
      helplessness. Naive rats subchronically treated with imipramine showed a tendency
      toward increased expression of MAP-2, but those treated with fluvoxamine did not.
      These results indicate that the neuroplasticity-related proteins synapsin I, GAP
      43, and MAP-2 may play a role in the pathophysiology of depression and the
      mechanisms of antidepressants.

PMID- 16814934
TI  - Characteristics of adolescent past-year gamblers and non-gamblers in relation to
      alcohol drinking.
AB  - A preliminary examination of mental health and gambling characteristics as a
      function of alcohol use in adolescents was conducted in a nationally
      representative sample of 16- and 17-year-olds using data from the 1998 Gambling
      Impact and Behavior Study. Adolescents were stratified by past-year alcohol use
      into abstainers/low-frequency (ALF) drinkers and moderate to high-frequency (MHF)
      drinkers as done previously [Desai, R. A., Maciejewski, P. K., Pantalon, M. V., &
      Potenza, M. N. (in press). Gender differences among recreational gamblers:
      Association with the frequency of alcohol use. Psychology of Addictive
      Behaviors]. A greater proportion of MHF drinkers reported past-year gambling than
      did ALF drinkers (66.1% vs. 38.2%). In the ALF drinking group but not the MHF
      one, past-year gambling was associated with dysphoria/depression (odds ratio for
      ALF: 1.94, odds ratio for MHF: 0.88) and drug use (odds ratio for ALF: 2.57, odds
      ratio for MHF: 0.49). A significant gambling-by-alcohol-use group interaction was
      observed for drug use (p<0.01). Among past-year gamblers, MHF drinkers were more
      likely than ALF ones to report frequent gambling. These results suggest a complex
      relationship between gambling alcohol use, drug use, and mental health in
      adolescents.

PMID- 16814935
TI  - Alcohol use and tobacco abstinence among adolescents in cessation treatment:
      preliminary findings.
AB  - Although adult alcohol use is negatively associated with tobacco cessation, this
      relationship has not been reported for adolescents. We assessed the relationship
      between alcohol use and point prevalence abstinence from smoking in a sample of
      tobacco-dependent adolescents undergoing cessation treatment. Alcohol use both at
      baseline and) during tobacco cessation treatment was examined as predicting
      smoking abstinence in 101 adolescents (age=15.1years, S.D.=1.31years; age at
      first cigarette=11.3years, S.D.=1.93years; age at first drink=12.01years,
      S.D.=2.87years) attending a total of 642 treatment visits. Mixed regression
      analysis showed that participants who reported alcohol use during tobacco
      cessation treatment were significantly less likely to abstain from tobacco
      smoking (OR=0.42, 95% CI=0.23-0.78, t=-2.78, df=540, p=0.0057). However, pre
      enrollment alcohol use was not significantly associated with either short- or
      long-term tobacco abstinence. If confirmed in a larger group of adolescents, our
      findings suggest that youths attempting to quit smoking should abstain from
      alcohol.

PMID- 16814936
TI  - Prevalence of cocaine and marijuana use in the last trimester of adolescent
      pregnancy: socio-demographic, psychosocial and behavioral characteristics.
AB  - OBJECTIVE: To evaluate the prevalence of cocaine and marijuana use during the
      third trimester of pregnancy in a population of 1000 teenage women of a public
      hospital in Sao Paulo, Brazil using hair analysis in order to avoid
      underestimation of data that could happen by the use of self-report
      questionnaires and describe socio-demographic, psychosocial and behavioral
      characteristics of the drug users. RESULTS: Hair analysis has detected use of
      cocaine and/or marijuana in the third trimester of pregnancy in 6% of the
      patients: 4.0% used marijuana, 1.7% used cocaine and 3% used both drugs. They
      were about 17 years old, from low-income, poorly educated, unemployed,
      financially dependent and they had not planned the pregnancy. 10% of miscarriages
      have occurred in this population. CONCLUSION: This study shows the psychosocial
      impairment associated to teenage pregnancy and use of cocaine and marijuana
      during gestation by this low-income population with reliable data of prevalence
      obtained through hair analysis.

PMID- 16814937
TI  - Subjective effects of additional doses of buprenorphine in patients on
      buprenorphine maintenance.
AB  - OBJECTIVES: Buprenorphine has considerable abuse potential. Patients who are
      maintained on buprenorphine (for opioid dependence) further use additional doses
      besides its maintenance dose. Subjective effects of the additional doses of
      buprenorphine in patients on buprenorphine maintenance patients is focused in
      this study. METHODS: Nineteen subjects who were maintained on buprenorphine 4mg,
      s/l per day for at least 1month were admitted and given three additional doses of
      buprenorphine 2mg, s/l at the interval of 2h each and subjective effects were
      assessed with the help of standard tools after 2h of each dose and the next day
      also. Drug was given in a cumulative dose design in the inpatient unit of a de
      addiction centre. RESULTS: Dysphoria and sleepiness increased while euphoria and
      drug liking decreased with additional doses of buprenorphine. These changes were
      statistically significant and were highest at maximum cumulative dose of 10mg.
      CONCLUSION: Results suggest that abuse liability of buprenorphine in these
      subjects is low in higher doses. However, these findings need to be replicated in
      this group of patients to make a comment on clinical implication.

PMID- 16814938
TI  - A new theory of cryptogenic stroke and its relationship to patent foramen ovale;
      or, the puzzle of the missing extra risk.
AB  - Cryptogenic stroke (or stroke of undetermined cause) is a common cause of stroke
      and is statistically associated with patent foramen ovale (PFO). The largest
      study of cryptogenic stroke is the Homma study, which is a sub-study of the WARSS
      trial; it produced the following data: cryptogenic stroke patients with and
      without PFO, when treated with either aspirin or warfarin, all had identical
      recurrence rates. This is puzzling because it seems as though there ought to have
      been some extra risk in one of the two groups under one of the two treatments.
      How could everything come out the same? A review of the epidemiology of
      cryptogenic stroke shows that, compared to patients with stroke of determined
      cause, cryptogenic stroke patients are a little younger and have lower doses of
      the usual risk factors (hypertension and diabetes mellitus) but more PFO.
      Cryptogenic strokes appear to be embolic strokes from an unknown source. A
      previously published article setting forth a hypothetical theory of stress
      induced stroke was used to analyze these data. It is suggested that stress can
      induce episodic systemic platelet activation and hypercoagulability, which causes
      transient thrombus formation and subsequent embolization on both the arterial and
      venous sides of the circulation; the latter requires a PFO to cause a stroke
      (paradoxical embolism). The sum of these two mechanisms explains cryptogenic
      stroke. The PFO subset of cryptogenic stroke includes patients with both early
      and late stage disease who have an aggregate risk approximately equal to that of
      patients without PFO. Cryptogenic stroke is part of the disease of stress-induced
      cerebrovascular disease. Aspirin and warfarin have already been shown to be
      equally effective in secondary prevention of ischemic stroke.

PMID- 16814939
TI  - The role of excessive volume expansion in the pathogenesis of preeclampsia.
AB  - Preeclampsia is a disorder which is responsible for significant maternal
      morbidity and mortality as well as fetal wastage. Its pathogenesis remains
      obscure and its only treatment is the delivery of the placenta and the fetus.
      Over time it has become clear that this syndrome is not a single disease but a
      disorder with, most likely, multiple etiologic factors that have a common (or
      similar) phenotype(s). A leading hypothesis, first developed in the early 1970s,
      is that the hypertension, proteinuria and intrauterine growth restriction are the
      result of hypoperfusion of the maternal-fetal unit. However, the early events
      leading to this deranged circulatory event have not been extensively studied. We
      hypothesize that at least one of the early pathogenetic events is excessive
      expansion of the extracellular fluid volume. This leads to persistent elaboration
      of (a) circulating factor(s) that interfere(s) with remodeling of the decidual
      vasculature preventing normal placentation from occurring. Our experiments have
      dealt largely with the role that an endogenous bufadienolide, marinobufagenin
      (MBG), plays in this pathogenetic process. In this report, we provide evidence
      for this thesis and point to future studies aimed at testing this hypothesis.
      These will include evaluating large groups of preeclamptic patients to determine
      their blood and urinary levels of MBG. Efforts will also be made to determine if
      there are differences in sodium handling in those patients with elevated levels
      of MBG, compared to other preeclamptic patients and to normal pregnant subjects.

PMID- 16814940
TI  - Stem cells: new cell source for myocardial constructs tissue engineering.
AB  - Cardiovascular diseases like myocardial infarction, complex congenital heart
      disease, and subsequent heart failure are a leading cause of morbidity and
      mortality. Recent advances in tissue engineering arise to address the lack of
      available tissues and organs for transplantation because cells alone are not
      capable of recreating complex tissues upon transplantation. Consequently, a very
      promising approach to repair large scar areas and congenital heart defects may be
      the use of tissue engineering, in which cells are seeded in three-dimensional
      matrices of biodegradable polymers to form myocardial constructs. In recent
      years, there has been a tremendous increase in the understanding of stem cell
      biology. Stem cells have clonogenic and self-renewing capabilities, and under
      certain conditions, can differentiate into multiple cell lineages. Recent studies
      have shown that stem cells can be isolated from a wide variety of tissues,
      including bone marrow, peripheral blood, muscle, and adipose tissue. We
      hypothesize that tissue-engineered myocardial constructs with stem cells may
      fulfill the requirements of native heart muscle and, in the long run, may allow
      replacement of the injured heart and repair of congenital cardiac defects
      possible.

PMID- 16814941
TI  - An experiential mind-body approach to the management of medically unexplained
      symptoms.
AB  - This article outlines an experiential mind-body framework for understanding and
      treating patients with medically unexplained symptoms. The model relies on
      somatic awareness, a normal part of consciousness, to resolve the mind-body
      dualism inherent in conventional multidisciplinary approaches. Somatic awareness
      represents a guiding healing heuristic which allows for a linear treatment
      application of the biopsychosocial model. The heuristic acknowledges the validity
      of the patient's physical symptoms and identifies psychological and social
      factors needed for the healing process. Somatic awareness is used to direct
      changes in coping styles, illness beliefs, medication dependence and personal
      dynamics that are necessary to achieve symptom control. The mind-body concept is
      consistent with and supported by neurobiological models which draw on central
      nervous system mechanisms to explain medically unexplained symptoms. The concept
      is also supported by a recent hypothesis concerning the role peripheral
      connective tissue may play in influencing illness and well-being. Finally,
      somatic awareness is described as having potential to enhance understanding and
      conscious use of inner healing mechanisms at the basis of the placebo effect.

PMID- 16814942
TI  - The thrombophilic fetus.
AB  - Thrombophilia is the increased tendency to thrombosis. Inherited and acquired
      factors may determine thrombophilia. Some physiologic conditions, such as
      pregnancy are themselves "thrombophilic". In pregnancy, in fact, there is a
      decrease of all natural anticoagulant systems, such as antithrombin, protein C
      and protein S that are partially compensated by an increased fibrinolysis. It has
      been well established that women with thrombophilic disorders are at greater risk
      of venous thromboembolism in pregnancy and puerperium. It has also been observed
      that those women have higher prevalence of those obstetric complications in which
      microplacental thrombosis may play a pathogenetic role, such as placental
      abruption, preeclampsia, intrauterine growth restriction, intrauterine fetal
      death, repeated spontaneous miscarriage. Given that those complications are not
      always associated with maternal thrombophilia, controversy still exists on the
      exact impact of the disorders with the adverse pregnancy outcomes. While we are
      convinced that thrombophilias are extensively implicated in pregnancy
      complications, we feel that there has not been completely elucidated the role of
      the different factors, the gestational age at which those factors may intervene,
      nor has been given enough relevance to the weight of fetal thrombophilias in the
      origin of some specific form of those obstetric complications. We should bear in
      mind that some thrombophilias may be inherited from the mother, the father or
      both. Our hypothesis is that maternal thrombophilias may be responsible for
      venous thromboembolism, preeclampsia HELLP and eclampsia, whereas fetal
      thrombophilia, may account for IUGR or stillbirth. This last would also explain
      some stillbirth or repeated late (>10 gestational weeks) miscarriage observed in
      non-thrombophilic mothers. The two sides of thrombophilia may, of course, concur,
      resulting in the more severe clinical presentations.

PMID- 16814943
TI  - Enhanced scavenging of lipid substances is a possible effect of corticosteroids
      in the treatment of cholesterol crystal embolism.
AB  - Cholesterol crystal embolism (CCE) is a systemic refractory disease especially
      prevalent amongst elderly patients suffering from atherosclerosis. Treatment of
      this condition remains controversial due to difficulties in diagnosis.
      Corticosteroid therapy may be an important treatment option despite its elusive
      mechanisms. To clarify the role of corticosteroid in CCE therapy, we collected
      the samples from six autopsied subjects with CCE, three of whom were clinically
      given various doses of corticosteroid to investigate stable atherosclerosis
      related substances, advanced glycation end-products (AGE), and several AGE
      receptors such as scavenger receptor class B type 1 (SR-B1), receptor for AGE
      (RAGE), and galectin-3 in the liver tissues and atherosclerotic areas by
      immunostaining using a tissue macro-array technique. An intense expression of AGE
      and its receptors was identified in the enlarged Kupffer cells of CCE cases,
      which were given relatively high doses of corticosteroid. In addition, numerous
      mononuclear cells in the intimal atheromatous plaque presented strong expressions
      of AGE and SR-B1. In conclusion, we speculated that corticosteroid treatment for
      CCE may upregulate the activations, including phagocytic capacity of Kupffer
      cells mediated by overexpression of RAGE and scavenger receptors, resulting in
      efficient clearance of the lipid substances from the blood circulation released
      from atherosclerotic areas.

PMID- 16814944
TI  - MUC4 expression and its relation to ErbB2 expression, apoptosis, proliferation,
      differentiation, and tumor stage in non-small cell lung cancer (NSCLC).
AB  - There is a peptide sequence homology between the gene product of human MUC4 and
      rat Muc4/sialomucin complex (SMC). Each contains a transmembrane subunit with two
      epidermal growth factor (EGF)-like domains that act as ligand for ErbB2. MUC4 and
      ErbB2 mediate intracellular signaling pathways that are linked to repression of
      apoptosis and either to proliferation or to differentiation of tumor cells. This
      study investigates the expression of human MUC4 in neoplastic and corresponding
      non-neoplastic tissues, and the relation of MUC4 expression in neoplastic tissues
      to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage
      in a series of 100 non-small cell lung carcinomas (NSCLCs). MUC4 and ErbB2
      expressions and cell proliferation (PCNA) were shown using immunohistochemistry.
      Apoptotic index (AI) and tumor differentiation were determined by morphologic
      criteria. All the non-neoplastic bronchial tissues and 85% of NSCLCs showed MUC4
      expression. MUC4 expression was found to be higher in neoplastic than in non
      neoplastic tissues (Yates correction p: 0.0006). MUC4 expression was inversely
      correlated with AI (p=0.0002) and was correlated with ErbB2 expression (p=0.022),
      but not with PCNA counts and tumor stage. Our results indirectly suggest that
      MUC4, in association with ErbB-2, might be involved in the repression of
      apoptosis and differentiation rather than proliferation in tumor cells of NSCLCs.

PMID- 16814945
TI  - Epithelioid and sarcomatoid malignant pleural mesothelioma in endoscopic gastric
      biopsies: a diagnostic pitfall.
AB  - Pleural malignant mesothelioma (MM) usually presents with chest pain, pleural
      effusion, or cough in middle-aged and elderly individuals with a history of
      asbestos exposure, but may rarely present at unusual metastatic sites. The
      luminal gastrointestinal (GI) tract is only rarely involved in patients with wide
      spread disease at autopsy. Encountering MM in endoscopic GI biopsies is an
      exceptionally rare event in surgical pathology practice and may therefore pose
      great diagnostic challenges if not considered, in particular if the clinical
      history is not informative or the GI symptoms are the presenting signs of the
      disease. To our knowledge, only three cases of epithelioid mesothelioma (EM)
      involving the luminal GI tract (intestine) have been reported so far, but no case
      of sarcomatoid MM (SM) involving the GI mucosa has been described. We herein
      present the first two cases of MM (one each of EM and SM) of the pleura,
      presenting in endoscopic gastric biopsies as small polypoid lesions and poorly
      healing ulcers 30 and 35 months after the initial diagnosis of pleural MM,
      respectively. The major differential diagnoses encompass primary or metastatic
      adenocarcinoma in case one and cytokeratin-positive (KIT negative!) GI stromal
      tumors (GISTs) and sarcomatoid carcinoma in case two, as well as other rare
      entities.

PMID- 16814946
TI  - A pathology-based substrate for target definition in radiosurgery of brain
      metastases.
AB  - PURPOSE: To investigate the need of a margin other than for accuracy reasons in
      stereotactic radiosurgery (SRS) of brain metastases by means of histopathology.
      METHODS AND MATERIALS: Evaluation of 45 patients from two pathology departments
      having had brain metastases and an autopsy of the brain. Growth patterns were
      reviewed with a focus on infiltration beyond the metastases boundary and made
      visible with immunohistochemical staining: the metastasis itself with tumor
      specific markers, surrounding normal brain tissue with a glial marker, and a
      possible capsule with a soft tissue marker. Measurements were corrected by a
      tissue-shrinkage correction factor taken from literature. Outcomes parameters for
      infiltration were mean and maximum depths of infiltration and number of measured
      infiltration sites. RESULTS: In 48 of 76 metastases, an infiltration was present.
      The largest group of metastases was lung cancer. Small-cell lung cancer (SCLC)
      and melanoma showed a maximum depth of infiltration of > or =1 mm, and other
      histologies <1 mm. For non-small-cell lung cancer (NSCLC), melanoma, and sarcoma,
      the highest number of infiltrative sites were observed (median, 2; range, 1-8).
      SCLC showed significantly larger infiltrative growth, compared with other
      diagnostic groups. In NSCLC, the highest percentage of infiltration was present
      (70%). CONCLUSIONS: Infiltrative growth beyond the border of the brain metastasis
      was demonstrated in 63% of the cases evaluated. Infiltrative growth, therefore,
      has an impact in defining the clinical target volume for SRS of brain metastases,
      and a margin of approximately 1 mm should be added to the visible lesion.

PMID- 16814947
TI  - A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan
      in combination with protracted venous infusion 5-fluorouracil, for resectable
      locally advanced rectal cancer.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and tolerance of
      preoperative chemoradiotherapy (CRT) with irinotecan (CPT-11) and 5-fluorouracil
      (5-FU) in patients with resectable rectal cancer. METHODS AND MATERIALS: Patients
      with resectable T3-T4 rectal cancer and Eastern Cooperative Oncology Group
      performance status <2 were included. CPT-11 (50 mg/m(2) weekly) and 5-FU (225
      mg/m(2)/day continuous infusion, 5 days/week) were concurrently administered with
      radiation therapy (RT) (45 Gy, 1.8 Gy/day, 5 days/week), during 5 weeks. RESULTS:
      A total of 74 patients were enrolled: mean age, 59 years (20-74 years; SD, 11.7).
      Planned treatment was delivered to most patients (median relative dose intensity
      for both drugs was 100%). Grade 3/4 lymphocytopenia occurred in 35 patients
      (47%), neutropenia in 5 (7%), and anemia in 2 (3%). Main Grade 3 nonhematologic
      toxicities were diarrhea (14%), asthenia (9%), rectal mucositis (8%), and
      abdominal pain (8%). Of the 73 resected specimens, 13.7% (95% confidence interval
      [CI], 6.8-23.7) had a pathologic complete response and 49.3% (95% CI, 37.4-61.3)
      were downstaged. Additionally, 66.7% (95% CI, 51.1-80.0) of patients with
      ultrasound staged N1/N2 disease had no pathologic evidence of nodal involvement
      after CRT. CONCLUSIONS: This preoperative CRT schedule has been shown to be
      effective and feasible in a large population of patients with resectable rectal
      cancer.

PMID- 16814948
TI  - First-year PSA kinetics and minima after prostate cancer radiotherapy are
      predictive of overall survival.
AB  - PURPOSE: We analyzed whether first-year prostate-specific antigen (PSA) kinetics
      and minima are predictive of overall survival (OS). METHODS AND MATERIALS: The
      data set contained 1,174 patients treated with external beam radiotherapy (RT)
      from 1987 to 2001. The relative rate of change (lambda) in post-RT PSA values
      during the first year (13.5 months) was computed using regression analysis of
      ln(PSA) vs. time. We also computed the PSA minimum (mPSA) reached during the same
      period. Recursive partitioning analysis was used to identify the relevant
      cutpoints for the factors being investigated for its association with survival:
      age, pretreatment PSA, radiation dose, relative rate of change in PSA post-RT,
      and 1-year PSA minimum. For each of the other factors stage, Gleason score and
      risk group, all possible cutpoints were considered in the multivariate analyses.
      Significant factors were considered in the multivariate analyses to identify
      independent predictors for overall survival. RESULTS: The median value of lambda
      was -1.0 years(-1) (range, -11.0-5.1 years(-1)). The 1-year minimum had a median
      of 0.8 ng/mL (range, 0.01-30.9 ng/mL). Recursive partitioning analysis and Cox
      proportional hazards analyses identified the following pretreatment or treatment
      factors adversely related to OS: age, Gleason score, stage, and dose. First-year
      mPSA > or = 4 ng/mL and lambda > 0 were post-RT independent prognostic factors
      for worse OS. CONCLUSION: First-year post-RT PSA kinetics and minima are early
      response parameters predictive of overall survival for prostate cancer patients.
      These factors may be useful in selecting patients for early salvage therapy.

PMID- 16814949
TI  - Bcl-2 and bax expression and prostate cancer outcome in men treated with
      radiotherapy in Radiation Therapy Oncology Group protocol 86-10.
AB  - PURPOSE: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation;
      yet abnormal expression of either has been associated with failure after
      radiotherapy (RT). In this study we examined bcl-2 and bax expression as
      predictive markers in men treated with radiotherapy +/- androgen deprivation on
      Radiation Therapy Oncology Group (RTOG) protocol 86-10. EXPERIMENTAL DESIGN:
      Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl
      2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards
      multivariate analysis was used to determine the relationship of abnormal bcl-2
      and bax expression to the end points of local failure, distant metastasis, cause
      specific mortality, and overall mortality. Bcl-2 overexpression was classified as
      any tumor cell cytoplasmic staining and altered bax expression was classified as
      greater or lesser cytoplasmic staining intensity of tumor cells as compared with
      adjacent normal prostate epithelium. RESULTS: The study cohort exhibited bcl-2
      overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n =
      49) of cases. A borderline significant relationship was observed between abnormal
      bax expression and higher Gleason score (p = 0.08). In univariate and
      multivariate analyses, there was no statistically significant relationship seen
      between abnormal bcl-2 or bax expression and outcome. CONCLUSIONS: Abnormal bcl-2
      and bax expression were not related to any of the end points tested. The cohort
      examined was comprised of patients with locally advanced disease and it is
      possible that these markers may be of greater value in men with earlier-stage
      prostate cancer.

PMID- 16814950
TI  - Continuing evidence for poorer treatment outcomes for single male patients:
      retreatment data from RTOG 97-14.
AB  - PURPOSE: The specific aim of this study was to evaluate outcome differences by
      gender and partner status for patients treated on Radiation Therapy Oncology
      Group (RTOG) protocol 97-14. METHODS AND MATERIALS: RTOG 97-14 randomized
      patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1
      fraction or 30 Gy in 10 fractions. Retreatment rates and overall survival were
      made based upon gender, marital status, and Karnofsky Performance Status (KPS).
      The cumulative incidence method was used to estimate retreatment time at 36
      months from enrollment, and Gray's test was used to test for treatment
      differences within the same groupings. Marital status, gender, KPS, and treatment
      were variables tested in a univariate Cox model evaluating the time to
      retreatment. RESULTS: Married men and women and single women receiving 30 Gy had
      significantly longer time to retreatment, p = 0.0067, p = 0.0052, and p = 0.0009
      respectively. We failed to show a difference in retreatment rates over time in
      single men receiving either 30 Gy or 8 Gy. Univariate analysis of the entire
      group determined patients receiving 30 Gy in 10 fractions significantly less
      likely to receive retreatment, p < 0.0001, with a trend toward single patients
      less likely to be re-treated, p = 0.07. CONCLUSION: Non-disease-related
      variables, such as social support, might influence the results of clinical trials
      with subjective endpoints such as retreatment rates. The statistically
      nonsignificant difference in the 36-month retreatment rates observed in single
      male patients receiving 8 Gy may be a result of inadequate social support systems
      in place to facilitate additional care. Patients receiving 8 Gy in a single
      fraction had significantly higher retreatment rates compared with patients
      receiving 30 Gy in 10 fractions.

PMID- 16814951
TI  - A prospective study of reduced-dose three-course CHOP followed by involved-field
      radiotherapy for patients 70 years old or more with localized aggressive non
      Hodgkin's lymphoma.
AB  - PURPOSE: We conducted a multicenter prospective study to evaluate the efficacy
      and safety of reduced-dose three-course CHOP (cyclophosphamide, doxorubicin,
      vincristine, and prednisolone) followed by involved-field radiotherapy for
      elderly patients with localized aggressive non-Hodgkin's lymphoma. The primary
      endpoint was compliance with the combined modality. METHODS AND MATERIALS: This
      study included untreated patients, > or =70 years old, with diffuse aggressive
      lymphoma, Stage IA or contiguous nonbulky Stage IIA. 80%-CHOP (cyclophosphamide
      600 mg/m(2), doxorubicin 40 mg/m(2), vincristine 1.1 mg/m(2), and prednisolone at
      80 mg/day for 5 days) was repeated every 3 weeks. After three cycles of
      chemotherapy, involved-field radiotherapy was performed with a radiation dose of
      30-50 Gy in 15-28 fractions. RESULTS: Twenty-four patients with a median age of
      75 years (range, 70-84 years) were enrolled. The compliance rate of the protocol
      study was 87.5% (95% confidence interval [CI], 67.6-97.3). Three patients
      received only two cycles of chemotherapy because of toxicity or second neoplasm.
      There were no deaths caused by severe toxicity. The 3-year progression-free and
      overall survival rates were 83.1% (95% CI, 75.4-90.8) and 82.9% (95% CI, 75.1
      90.6), respectively. CONCLUSION: Three-course 80%-CHOP followed by involved-field
      radiotherapy may be safe for administration to elderly patients over 70 years
      old. The next step is to evaluate three-course 80%-CHOP and rituximab followed by
      radiotherapy in elderly patients with localized disease.

PMID- 16814952
TI  - Trends in the use of postoperative radiotherapy for resected non-small-cell lung
      cancer.
AB  - PURPOSE: A 1998 meta-analysis of postoperative radiotherapy (PORT) for non-small
      cell lung cancer (NSCLC) found that PORT did not improve outcomes. Yet practice
      guidelines differ in their recommendations with regard to PORT use. We examine
      temporal trends in PORT use before and after the 1998 meta-analysis. METHODS AND
      MATERIALS: Using data from the Surveillance, Epidemiology, and End Results (SEER)
      Program, we identified 22,953 patients with Stage I, II, or IIIA NSCLC who had
      resection between 1992 and 2002 in the United States and characterized each
      patient according to nodal status (N0, N1, or N2 disease). We measured use of
      PORT by calendar year. We examined the association between clinical and
      demographic characteristics and receipt of PORT using logistic regression.
      RESULTS: For N0, N1, and N2 NSCLC, PORT use has declined. The proportion of
      patients with N0 disease receiving PORT declined from 8% in 1992 to 4% in 2002.
      For patients with N1 disease, PORT use declined from 51% in 1992 to 19% in 2002;
      and for patients with N2 disease, PORT use declined from 65% in 1992 to 37% in
      2002. CONCLUSION: In the context of uncertainty about what constitutes optimal
      adjuvant treatment for resected NSCLC, PORT use has substantially declined.

PMID- 16814953
TI  - Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: a
      retrospective study from the Rare Cancer Network.
AB  - PURPOSE: The aim of this study was to assess the outcome in patients with
      cerebellar glioblastoma (GBM) treated in 15 institutions of the Rare Cancer
      Network. METHODS AND MATERIALS: Data from a series of 45 adult patients with
      cerebellar GBM were collected in a retrospective multicenter study. Median age
      was 50.3 years. Brainstem invasion was observed in 9 (20%) patients. Radiotherapy
      (RT) was administered to 36 patients (with concomitant chemotherapy, 7 patients).
      Adjuvant chemotherapy after RT was administered in 8 patients. Median RT dose was
      59.4 Gy. Median follow-up was 7.2 months (range, 3.4-39.0). RESULTS: The 1-year
      and 2-year actuarial overall survival rate was 37.8% and 14.7%, respectively, and
      was significantly influenced by salvage treatment (p = 0.048), tumor volume (p =
      0.044), extent of neurosurgical resection (p = 0.019), brainstem invasion (p =
      0.0013), additional treatment after surgery (p < 0.001), and completion of the
      initial treatment (p < 0.001) on univariate analysis. All patients experienced
      local progression: 8 and 22 had progression with and without a distant failure,
      respectively. The 1- and 2-year actuarial progression free survival was 25% and
      10.7%, respectively, and was significantly influenced by brainstem invasion (p =
      0.002), additional treatment after surgery (p = 0.0016), and completion of the
      initial treatment (p < 0.001). On multivariate analysis, survival was negatively
      influenced by the extent of surgery (p = 0.03) and brainstem invasion (p = 0.02).
      CONCLUSIONS: In this multicenter retrospective study, the observed pattern of
      failure was local in all cases, but approximately 1 patient of 4 presented with
      an extracerebellar component. Brainstem invasion was observed in a substantial
      number of patients and was an adverse prognostic factor.

PMID- 16814954
TI  - Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer
      patients: consequential late damage.
AB  - PURPOSE: Late gastrointestinal (GI) toxicity after radiotherapy can be partly
      explained by late effects of acute toxicity (consequential late damage). We
      studied whether there is a direct relationship between acute and late GI
      toxicity. PATIENTS AND METHODS: A total of 553 evaluable patients from the Dutch
      dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes
      for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity,
      2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a
      multivariable model, late endpoints (overall toxicity and five toxicity
      indicators) were studied as a function of acute toxicity, pretreatment symptoms,
      and relevant dose parameters. RESULTS: At multivariable analysis, AMD and acute
      proctitis were strong predictors for overall toxicity, "intermittent bleeding,"
      and "incontinence pads" (p < or = 0.01). For "stools > or =6/day" all three were
      strong predictors. No significant associations were found for "severe bleeding"
      and "use of steroids." The predictive power of the dose parameters remained at
      the same level or became weaker for most late endpoints. CONCLUSIONS: Acute GI
      toxicity is an independent significant predictor of late GI toxicity. This
      suggests a significant consequential component in the development of late GI
      toxicity.

PMID- 16814955
TI  - Effect of distance to radiation treatment facility on use of radiation therapy
      after mastectomy in elderly women.
AB  - PURPOSE: We sought to study the effect of distance to the nearest radiation
      treatment facility on the use of postmastectomy radiation therapy (PMRT) in
      elderly women. METHODS AND MATERIALS: Using data from the linked Surveillance,
      Epidemiology, and End Results-Medicare (SEER-Medicare) database, we analyzed
      19,787 women with Stage I or II breast cancer who received mastectomy as
      definitive surgery during 1991 to 1999. Multivariable logistic regression was
      used to investigate the association of distance with receipt of PMRT after
      adjusting for clinical and sociodemographic factors. RESULTS: Overall 2,075
      patients (10.5%) treated with mastectomy received PMRT. In addition to cancer and
      patient characteristics, in our primary analysis, increasing distance to the
      nearest radiation treatment facility was independently associated with a
      decreased likelihood of receiving PMRT (OR = 0.996 per additional mile, p =
      0.01). Secondary analyses revealed that the decline in PMRT use appeared at
      distances of more than 25 miles and was statistically significant for those
      patients living more than 75 miles from the nearest radiation facility (odds of
      receiving PMRT of 0.58 [95% CI = 0.34-0.99] vs. living within 25 miles of such a
      facility). The effect of distance on PMRT appeared to be more pronounced with
      increasing patient age (>75 years). Variation in the effect of distance on
      radiation use between regions of the country and nodal status was also
      identified. CONCLUSIONS: Oncologists must be cognizant of the potential barrier
      to quality care that is posed by travel distance, especially for elderly
      patients; and policy makers should consider this fact in resource allocation
      decisions about radiation treatment centers.

PMID- 16814956
TI  - Antibacterial and allelopathic activity of methanolic extract from Iris
      pseudopumila rhizomes.
AB  - The methanolic extract of rhizomes of Iris pseudopumila was tested for its
      antibacterial and allelopathic activity. The extract was shown to have
      antibacterial effects. The allelopathic effect was tested against Raphanus
      sativus seed germination. The extract caused a decrease in the percentage of seed
      germination and root and epicotyl growth.

PMID- 16814957
TI  - Larvicidal activity of saponin containing extracts and fractions of fruit
      mesocarp of Balanites aegyptiaca.
AB  - Chloroform, ethyl acetate, butanol and methanol extracts of fruit mesocarp of
      Balanites aegyptiaca and five fractions from the methanol extract were tested
      against the Aedes aegypti mosquito larvae. All extracts showed larvicidal effects
      however the highest larval mortality was found in methanol extract. One fraction
      obtained from the silica gel column chromatography of the latter was found most
      effective for larval mortality. This fraction also interfered with adult
      emergence. A concentration of 0.0014% (w/v) of this active fraction showed
      inhibition of the 50% of the test larval population from emerging adults
      (EC(50)). The analysis of total saponin content of these tested extracts and
      fractions revealed a strong correlation between saponin content and larval
      mortality.

PMID- 16814958
TI  - Antiinflammatory activity of Polygala japonica extract.
AB  - The antiinflammatory activity of the aqueous extract of Polygala japonica (AEPJ)
      was investigated in mice and rats to find the pharmacological basis for its
      ethnomedical use. The extract produced a significant inhibition of peritoneal and
      cutaneous vascular permeability induced by acetic acid and histamine,
      respectively and ear swelling induced by picryl chloride in mice at the dose of
      25.0 mg/kg. Moreover, the extract markedly inhibited footpad edema induced by
      histamine in rats, and decreased prostaglandin E(2) (PGE(2)) content in
      carrageenan-induced air-pouch at doses of 12.5 and 6.25 mg/kg respectively.

PMID- 16814959
TI  - Apoptotic and free radical scavenging properties of the methanolic extract of
      Gentianella alborosea.
AB  - Gentianella alborosea ("Hercampure") is a Peruvian species used in folk medicine
      for the treatment of a variety of health disorders. We tested the free radical
      scavenging (DPPH) and induction of apoptosis on a human uterus tumor cell line
      (HeLa) by its methanolic extract. The results showed a noticeable radical
      scavenging activity and a dose-dependent apoptotic effect.

PMID- 16814960
TI  - Differentiation of bovine Staphylococcus aureus isolates by use of polymorphic
      tandem repeat typing.
AB  - Staphylococcus aureus is a common cause of bovine mastitis. A simple and
      efficient typing method would be helpful in understanding S. aureus sources and
      spread. Ninety-six S. aureus strains, isolated between 1961 and 2003 from the
      milk of 90 dairy cows belonging to 75 French herds, were subjected to multiple
      locus variable-number tandem repeats analysis (MLVA) by PCR. The conjunction of
      clfA, clfB, SAV1078 and fnb gene tandem repeats (TRs) enabled the definition of
      61 types. When coa, spa, sdrC, sdrD and sspA TRs were used individually as
      additional markers, 63, 68, 67, 65 and 67 types were defined, respectively,
      versus 77 types when they were all included in the method. These additional TRs
      did not improve the differentiation of isolates collected in the same farm. The
      MLVA procedure using the tandem repeats embedded in clfA, clfB, SAV1078 and fnb
      loci as a basic combination at the herd level or associated with other TRs such
      as spa, sdrC, sdrD, sspA and coa can be a valuable tool for bovine S. aureus
      epidemiological studies.

PMID- 16814961
TI  - Behavioral gender differences in the neonatal period according to the Brazelton
      scale.
AB  - The aim of the present study was to analyze gender differences in neonatal
      behavior. A sample of 188 healthy full-term newborns (88 boys and 100 girls) was
      assessed. The behavioral evaluations were performed using the Brazelton Neonatal
      Behavioral Assessment Scale (NBAS), when the infants were between 48 and 80 hours
      old. Girls had higher scores than boys in 4 out of the 34 behavioral items of the
      NBAS. These are the following: Orientation Animate Auditory (t=2.486; P=0.014),
      Alertness (t=2.546; P=0.012), Quality of Alertness (t=3.091; P=0.002), and State
      Regulation (t=2,343; P=0.020). Boys had higher scores in the Irritability item
      (t=-2.186; P=0.030). We have analyzed also the possible effects of the medication
      during delivery because mothers of boys were more likely to have used this
      medication but no differences have been found among the mentioned items. These
      results appear to confirm that similarities between boys and girls are much more
      the norm than differences related to gender, but even though they are quite
      subtle, differences do exist in the way newborn infants react and behave in the
      neonatal period.

PMID- 16814962
TI  - Lack of influence of mild hypothermia on amplitude integrated
      electroencephalography in neonates receiving extracorporeal membrane oxygenation.
AB  - OBJECTIVE: To observe amplitude integrated electroencephalography (aEEG) in
      neonates receiving ECMO and to determine whether mild hypothermia influenced the
      aEEG recording. METHODS: Twenty-six consecutive neonates enrolled in a pilot
      study of mild hypothermia during ECMO were studied. The first group (N=6) was
      maintained at 37 degrees C throughout the study period. Subsequent groups were
      cooled to 36 degrees C (N=4), 35 degrees C (N=5), and finally 34 degrees C (N=6)
      respectively for 24 h and the final group (N=5) to 34 degrees C for 48 h before
      being rewarmed to 37 degrees C. The aEEG was recorded continuously during the
      first 5 days of ECMO. The aEEG was classified as normal, moderately or severely
      suppressed and examined for the occurrence of seizures. To assess the effect of
      temperature, the aEEG was compared over 12 h during the final 6 h of cooling and
      during the first 6 h once infants were rewarmed. RESULTS: No change in aEEG
      amplitude was noted over the temperature range studied. Of the 26 traces
      obtained, 16 (62%) were normal throughout, 6 (23%) were intermittently moderately
      abnormal and 1 (14%) was severely abnormal. Three (11%) traces had periods of
      frequent seizure activity and these were not associated with clinical
      manifestations in two neonates. In one infant who suffered a cerebral
      haemorrhage, the aEEG became abnormal before cranial ultrasound abnormalities
      were apparent. CONCLUSIONS: Continuous cerebral monitoring with aEEG is feasible
      during ECMO and may add information to clinical examination. Mild hypothermia to
      34 degrees C for up to 48 h does not influence the aEEG suggesting that cerebral
      monitoring with aEEG is possible during mild hypothermia.

PMID- 16814963
TI  - 17beta-estradiol enhances contact hypersensitivity and IFN-gamma expression in
      inflamed skin of BALB/c mice.
AB  - The effects of 17beta-estradiol (E(2)) on mouse contact hypersensitivity (CHS)
      elicited at the ears by 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (OXA) were
      examined. Male and female BALB/c mice were sham-treated or gonadectomized, and
      then subcutaneously injected with E(2) twice a week for 4 weeks. The mice were
      sensitized by OXA application to their back and CHS was elicited at the ears.
      E(2) enhanced the ear swelling of all groups at 6h after the elicitation. E(2)
      had no effect on the mitogenesis of splenic lymphocytes or nitric oxide synthesis
      by peritoneal macrophages. E(2) increased the number of thymic cells in female
      mice, but not male mice, and had no effect on the splenic cells of either female
      or male mice. Evaluation of the cytokine expressions in the inflamed skin
      revealed that E(2) enhanced the expression of interferon-gamma, but had no effect
      on the expression of interleukin-4. These results suggest that E(2) affects the
      thymus and enhances the production of interferon-gamma in skin to augment the
      skin swelling in CHS elicited by OXA.

PMID- 16814964
TI  - Sensitivities of gel entrapped hepatocytes in hollow fibers to hepatotoxic drug.
AB  - The aim of this study was to determine the feasibility of detecting
      hepatotoxicity using gel entrapped hepatocytes in simple hollow fibers. Four
      typical hepatotoxic drugs were tested for hepatotoxicity in gel entrapped
      hepatocyte as opposed to hepatocyte monolayer, a hepatocyte system extensively
      used for hepatotoxicity studies in vitro. Hepatotoxicity or cell damage was
      assessed by the methyl tetrazolium (MTT) assay, liver-specific functions and the
      intracellular glutathione (GSH) content. After exposure to acetaminophen,
      significant cell damage of gel entrapped hepatocytes was detected at 48 h while
      hepatocyte monolayer was not so sensitive except for albumin synthesis and this
      difference between two hepatocyte systems was similar on hepatotoxic response to
      antituberculosis drugs including rifampicin and isoniazid. At low concentrations
      of either rifampicin or isoniazid, time-dependent hepatotoxicity was only
      evidenced in gel entrapped hepatocytes after treatment and no cell damage
      occurred in hepatocyte monolayer at an incubation time as long as 96 h.
      Interestingly, hepatotoxicities of acetaminophen, isoniazid and rifampicin are
      all reportedly relevant to drug metabolisms of cytochrome P450. For sodium
      salicylate whose hepatotoxicity is unassociated to P450 activities, more
      significant reductions on cell viability and albumin synthesis at 5 mM than those
      at 1 mM apparently illustrated the concentration-dependent hepatotoxicities of
      gel entrapped hepatocytes as well as hepatocyte monolayer. It is highly suggested
      that gel entrapped hepatocyte are more sensitive in evaluation of
      hepatotoxicities than hepatocyte monolayer if this hepatotoxicity is related to
      drug metabolism. Thus, gel entrapment culture of hepatocytes with simple hollow
      fibers could be recommended for hepatotoxicity studies in vitro.

PMID- 16814965
TI  - Phenothiazine and carbazole-related compounds inhibit mitotic kinesin Eg5 and
      trigger apoptosis in transformed culture cells.
AB  - The effects of phenothiazine and carbazole derivatives on the cell-cycle
      progression of human transformed culture cells were analyzed. After 2 days
      incubation, 5 microM 1-phenethylamino-3-phenothiazin-10-yl-propan-2-ol (1)
      induced strong mitotic arrest followed by cell death, and 20 microM 1-(3,6
      dichloro-9H-carbazol-9-yl)-3-phenethylamino-2-propanol (5) and 1-(3,6-dibromo-9H
      carbazol-9-yl)-3-phenethylamino-2-propanol (6) also induced cell death. The TUNEL
      positive nuclei characteristic of apoptotic cell death were detected in cells
      treated with the compounds. We observed beta- and gamma-tubulins in the arrested
      cells after the addition of compound 1, and found that more than 90% of the
      mitotic cells exhibited the monoastral spindle instead of the normal bipolar
      spindle. The inhibitory effects of compounds 1, 5, and 6 on the microtubule
      activated ATPase activity of mitotic kinesin Eg5, which is essential for bipolar
      spindle formation, were obtained. The most effective inhibitor, compound 1, had
      an IC(50) of 1.52 microM. We also examined their toxicities on various cell
      lines. Compound 1 had less toxicity with the non-transformed cell line WI-38,
      whereas it exhibited strong toxicity with the transformed cell lines WI38VA13, HL
      60 and HeLa. On the other hand, a high dose of compound 6 caused cell death in
      both types of culture cells. These results suggest that compound 1, an Eg5
      inhibitor, selectively kills transformed culture cells.

PMID- 16814966
TI  - Induction of chromosome aberrations in cultured human lymphocytes treated with
      sand dust storm fine particles (PM2.5).
AB  - The clastogenic activity of airborne air fine particulate matter (PM2.5,
      particulates with an aerodynamic diameter < or =2.5 microm) has already been
      demonstrated. However little is known about the health risks associated with sand
      dust storm PM2.5 and its extract. In order to investigate the clastogenic
      activity of sand dust storm PM2.5 (include its organic and inorganic extract) on
      human lymphocytes, the normal PM2.5 and sand dust storm PM2.5 samples were
      collected in Wuwei city (Gansu Province) and Baotou city (Inner Mongolia), China.
      The chromosomal aberration (CA) test was employed and the cells were treated with
      0, 33, 100, 300 microg ml(-1) sand dust storm or normal ambient air PM2.5
      suspension (physiological saline as solvent control), or inorganic extract (0,
      75, 150, 300 microg ml(-1), physiological saline as solvent control) or organic
      extract (0, 20, 40, 80 microg ml(-1), DMSO as solvent control) at the beginning
      of the cell culture. The results indicated that sand dust storm PM2.5 and its
      extract as well as normal samples can induce increase in CA frequency. With the
      increase of treatment concentrations the CA frequency increased and the mitotic
      index (MI) values declined in a dose-response manner. In the same concentrates,
      the CA frequency of normal ambient air PM2.5 and its extract were significant
      higher than those of sand dust storm PM2.5 (P<0.05 or 0.01) except the treatment
      of Wuwei sample at higher doses (100, 300 microg ml(-1)), the treatment of
      inorganic extract of PM2.5 at the highest dose (300 microg ml(-1)) and the
      treatment of organic extract of PM2.5 at the higher dose (40 and 80 microg ml(
      1)) either in Baotou or in Wuwei (P>0.05). The toxicity of sand dust storm PM2.5
      and its extract at high dose is very potent. CA frequency of normal PM2.5
      (include its organic extract) from Baotou were higher than those of Wuwei
      especially in low and middle dose (P<0.05), but the treatment results of sand
      dust storm PM2.5 (include its all extract) was not significant different between
      the cities (P>0.05).

PMID- 16814968
TI  - Cryogenic liquids, nanoparticles, and microencapsulation.
AB  - The biopharmaceutical classification system (BCS) is used to group pharmaceutical
      actives depending upon the solubility and permeability characteristics of the
      drug. BCS class II compounds are poorly soluble but highly permeable, exhibiting
      bioavailability that is limited by dissolution. The dissolution rate of BCS class
      II drug substances may be accelerated by enhancing the wetting of the bulk powder
      and by reducing the primary particle size of the drug to increase the surface
      area. These goals may be achieved by nucleating drug particles from solution in
      the presence of stabilizing excipients. In the spray freezing into liquid (SFL)
      process, a drug containing solution is atomized and frozen rapidly to engineer
      porous amorphous drug/excipient particles with high surface areas and dissolution
      rates. Aqueous suspensions of nanostructured particles may be produced from
      organic solutions by evaporative precipitation into aqueous solution (EPAS). The
      suspensions may be dried by lyophilization. The particle size and morphology may
      be controlled by the type and level of stabilizers. In vivo studies have shown
      increased bioavailability of a wide variety of drugs particles formed by SFL or
      EPAS. For both processes, increased serum levels of danazol (DAN) were observed
      in mice relative to bulk DAN and the commercial product, Danocrine. Orally dosed
      itraconazole (ITZ) compositions, formed by SFL, produce higher serum levels of
      the drug compared to the commercial product, Sporanox oral solution.
      Additionally, nebulized SFL processed ITZ particles suspended in normal saline
      have been dosed via the pulmonary route and led to extended survival times for
      mice inoculated with Aspergillis flavus. SFL and EPAS processes produce amorphous
      drug particles with increased wetting and dissolution rates, which will
      subsequently supersaturate biological fluids in vivo, resulting in increased drug
      bioavailability and efficacy.

PMID- 16814967
TI  - Preparation of insulin nanoparticles and their encapsulation with biodegradable
      polyelectrolytes via the layer-by-layer adsorption.
AB  - To develop a new polypeptide delivery system, insulin nano-aggregates with sizes
      of 100-230nm were prepared by the salting out method with NaCl and encapsulated
      via the layer-by-layer (LbL) adsorption to provide the insulin nanoparticles
      shelled with two oppositely charged polyelectrolytes. Poly(alpha,beta-l-malic
      acid) (PMA) and water-soluble chitosan (WSC) as the weak polyelectrolytes with
      good biodegradability and biocompatibility in vivo were chosen to be the
      encapsulating materials of the LbL adsorption. In the preparation of the insulin
      nano-aggregates, the NaCl concentration and pH in the medium obviously affected
      yield and particle size of the insulin nano-aggregates. After eight adsorption
      cycles of the polyelectrolytes on the insulin nano-aggregates, the insulin
      polyelectrolyte nanoparticles with the sizes of 100-250nm were obtained with
      about 20% insulin loss. The insulin release from the nanoparticles was mostly pH
      dependent owing to sensitivity of the weak polyelectrolytes to pH. Insulin was
      hardly released from the nanoparticles in a medium at pH 4-5 while it could be
      released at pH 7.4, corresponding to the pH of the human blood and the body
      fluid. A burst effect was also observed although it could be reduced via
      increasing the polyelectrolyte layers of PMA and WSC assembled on insulin nano
      aggregates.

PMID- 16814969
TI  - A novel gel formation method, microstructure and mechanical properties of calcium
      polysaccharide gel films.
AB  - Hydrophilic gels, formed by the interaction of calcium ions with either sodium
      alginate or potassium pectinate, can be deposited as a wet coating on to the
      surface of drug loaded pellets. If the coated pellets are dried, they could be
      dispensed to a patient in a capsule for oral delivery of the active drug. In
      contact with the aqueous fluids of the gastrointestinal tract, the gel coat will
      rehydrate, swell and will sustain the release of active drug from the core. In
      order to facilitate the development and refinement of this novel coated system,
      it is beneficial to have a method that can produce free gel films in a manner
      that closely mimics the way the gel coat is formed and deposited on the pellet
      surface. Traditional film producing methods would involve the spraying or
      depositing (by evaporation) the gel forming polysaccharide on to an inert
      surface, drying it and then exposing the dry film to a solution containing
      calcium ions. Because the film is dry before it is gelled, it is fundamentally
      different to the wet gel coats that are deposited on to the pellets. We have
      developed a method to produce wet gel films and have evaluated different
      manufacturing conditions in order to optimize the quality of the completed gel
      film. Additionally, we have used these films to assess the effect that the type
      of polysaccharide and the environmental conditions experienced during rehydration
      (pH and ionic strength) has on the mechanical properties and the microscopic
      morphology of the gel. Irrespective of the rehydration medium, the calcium
      pectinate gel films were softer, weaker and more porous, than the calcium
      alginate films. Although calcium alginate gels that were rehydrated in 0.1M NaCl
      were porous, the same films rehydrated in either water, simulated gastric fluid
      USP (without pepsin) or 0.1M HCl were stronger and much more dense
      microscopically. Furthermore, of the four different alginates that were
      evaluated, those with a high content of guluronic acid saccharides were the
      strongest but most brittle when rehydrated in water.

PMID- 16814970
TI  - Neuronal organization of the rat inferior colliculus participating in four major
      auditory pathways.
AB  - The central nucleus of the inferior colliculus (CNIC) contains different types of
      neurons and is a source of ascending projection to the medial geniculate body
      (MGB), commissural projection to the contralateral IC, direct descending
      projection to the cochlea nucleus (CN) and indirect projection to the CN via the
      superior olivary complex (SOC). Using a retrograde tracing technique, we examined
      what kind of neurons and what percentage of neurons of each type recognized in
      the CNIC participated in the above-mentioned four projection pathways. We also
      examined whether the individual CNIC neurons send the collateral to the MGB, the
      contralateral IC, the CN and the SOC. In the present study, we demonstrated that
      the neurons participating in the four projections could be morphologically
      classified into two types of neurons with soma size variation. The percentages of
      neurons of each type differed among the four projection pathways. Using a double
      labeling technique, we found very few double-labeled neurons, indicating the
      collateral projections to the ipsilateral MGB and the contralateral IC. There
      were no double-labeled neurons in the collateral projections between the other
      combinations of targets. Therefore, we conclude that the ascending projection,
      the commissural projection and the descending projection to these targets arise
      from separate populations of neurons.

PMID- 16814971
TI  - From noise to pitch: transient and sustained responses of the auditory evoked
      field.
AB  - In recent magnetoencephalographic studies, we established a novel component of
      the auditory evoked field, which is elicited by a transition from noise to pitch
      in the absence of a change in energy. It is referred to as the 'pitch onset
      response'. To extend our understanding of pitch-related neural activity, we
      compared transient and sustained auditory evoked fields in response to a 2000-ms
      segment of noise and a subsequent 1000-ms segment of regular interval sound
      (RIS). RIS provokes the same long-term spectral representation in the auditory
      system as noise, but is distinguished by a definite pitch, the salience of which
      depends on the degree of temporal regularity. The stimuli were presented at three
      steps of increasing regularity and two spectral bandwidths. The auditory evoked
      fields were recorded from both cerebral hemispheres of twelve subjects with a 37
      channel magnetoencephalographic system. Both the transient and the sustained
      components evoked by noise and RIS were sensitive to spectral bandwidth.
      Moreover, the pitch salience of the RIS systematically affected the pitch onset
      response, the sustained field, and the off-response. This indicates that the
      underlying neural generators reflect the emergence, persistence and offset of
      perceptual attributes derived from the temporal regularity of a sound.

PMID- 16814972
TI  - New trends in hair analysis and scientific demands on validation and technical
      notes.
AB  - This review focuses on basic aspects of method development and validation of hair
      testing procedures. Quality assurance is a major issue in drug testing in hair
      resulting in new recommendations, validation procedures and inter-laboratory
      comparisons. Furthermore recent trends in research concerning hair analysis are
      discussed, namely mechanisms of drug incorporation and retention, novel
      analytical procedures (especially ones using liquid chromatography-mass
      spectrometry (LC-MS) and alternative sample preparation techniques like solid
      phase microextraction (SPME)), the determination of THC-COOH in hair samples,
      hair testing in drug-facilitated crimes, enantioselective hair testing procedures
      and the importance of hair analysis in clinical trials. Hair testing in
      analytical toxicology is still an area in need of further research.

PMID- 16814973
TI  - Microanatomy in 21 day rat brains exposed prenatally to cocaine.
AB  - We examined cell minicolumns, apical dendrite bundles, and inhibitory
      interneurons, in prefrontal and somatosensory cortex of 21-day-old rat brains
      exposed to cocaine during fetal development. Cell columns and apical dendrite
      bundles were found to be narrower, or closer together, in all three areas
      following in utero cocaine exposure. The inter-rater reliability among different
      observers was R(2)=0.89. The number of cells stained for glutamic acid
      decarboxylase (GAD) was not significantly different in the prenatal cocaine
      exposed group compared to saline controls. The present data suggests that
      recreational doses of cocaine administered intravenously in early pregnancy, have
      the capacity to modify the maturation of the ontogenetic cell column.

PMID- 16814974
TI  - Fetal development of membrane water channel proteins aquaporin-1 and aquaporin-4
      in the human brain.
AB  - Aquaporin-1 and aquaporin-4, water channel membrane proteins reported in both
      experimental animals and in adult humans, have been detected in different, non
      overlapping areas of the central nervous system. This immunohistochemical study
      describes the developmental expression pattern of the water channel membrane
      proteins, aquaporin-1 and aquaporin-4, in various structures of human fetal brain
      over the gestational period of 14-40 weeks. Aquaporin-1 immunostaining was
      exclusively found in the epithelial cells of the choroid plexus from the 14th
      gestational week, and the staining pattern altered slightly over time. At week
      14, immunostaining appeared only in the apical cell membranes. By the 18th
      gestational week, the entire plasma membrane of these apical cells was
      immunopositive, as well as was the cytosol. These changes in immunoreactivity
      indicate an increasing production of aquaporin-1 in the epithelial cells during
      the period between the 14th and 24th weeks of gestation. Aquaporin-4
      immunostaining was first detected in the archicortex, from gestational week 14
      and was detected in the neocortex, 6-7 weeks later. Immunostained structures were
      always astrocytes, particularly the astrocytic endfeet in the ventricular wall,
      at the developing ependymal lining, at the pial surface, and around the
      capillaries. Neuronal labeling was not observed. These results in human fetal
      brain lend morphological support to the previous findings that aquaporin-1 and
      aquaporin-4 play different roles in the regulation of the water homeostasis of
      the brain.

PMID- 16814975
TI  - Cloning and characterization of chicken growth hormone binding protein (cGHBP).
AB  - Growth hormone (GH) is indispensable for the growth of animals and its biological
      activity is mediated by binding to the growth hormone receptor (GHR) [Harvey S,
      Scanes CG, Daughaday WH. Growth hormone. Boca Raton: CRC Press; 1995]. GHR is a
      transmembrane protein responsible for signal transduction upon GH binding. GH
      also binds to the growth hormone binding protein (GHBP) which is the soluble form
      of GHR extracellular domain existing in circulation. Actions of GHBP include
      prolongation of GH bioavailability and prevention of GH signaling system from
      over-stimulation. To date, little is known about the mechanisms generating the
      chicken GHBP (cGHBP). Elucidating the genomic structure of cGHR will provide
      insights into such underlying mechanisms. Using polymerase chain reaction and
      library screening methods, we have characterized the genomic organization of
      chicken GHR (cGHR). The full-length coding region of the cGHR transcript is
      composed of eight exons (exons 2-10), lacking a human homolog exon 3 and spans at
      least 71 kb on the genome. A novel transcript of size 1.2kb was isolated from
      chicken liver total RNA using 5' and 3' rapid cDNA ends amplification (RACE). It
      was generated by utilizing a previously unknown polyadenylation signal located at
      the intron 6. Semi-quantitative reverse transcription polymerase chain reaction
      showed that this transcript is widely expressed in a variety of tissues. This
      transcript has an open reading frame comprising 203 amino acids. In vitro binding
      assay using ELISA demonstrated that Escherichia coli expressed recombinant
      protein encoded by this transcript was able to bind with chicken GH. Hence, this
      transcript is a potential candidate for cGHBP.

PMID- 16814976
TI  - One-year prospective quality-of-life outcomes in patients treated with
      angioplasty for symptomatic peripheral arterial disease.
AB  - BACKGROUND: Despite lower reported patency rates than open bypass, percutaneous
      transluminal angioplasty (PTA) may result in symptom relief, limb salvage,
      maintenance of ambulation and independent living, and overall improved quality of
      life. The goal of this study was to prospectively assess quality of life and
      functional outcomes after angioplasty and stenting in patients with chronic leg
      ischemia. METHODS: From August to December 2002, 84 patients with 118 chronically
      ischemic limbs underwent PTA with or without stenting as part of an ongoing
      prospective project performed to examine management of symptomatic peripheral
      arterial disease. All patients completed a preprocedure health questionnaire
      (Short Form 36) to provide adequate baseline data. Each patient was followed up
      every 3 months after treatment for 1 year to determine traditional outcomes of
      arterial patency, limb salvage, survival and amputation-free survival, and
      functional outcomes assessed according to improvement in quality of life,
      maintenance of ambulatory status, and maintenance of independent living status.
      The entire cohort was analyzed, as were subgroups of patients with lifestyle
      limiting claudication and those with critical limb ischemia. Outcomes were
      analyzed by using Kaplan-Meier life-table analysis, the log-rank test for
      survival curves, and the one-sample t test. A Cox proportional hazard model was
      used to determine whether presentation and level of disease were independent
      predictors of outcome. RESULTS: Of the 84 patients, 54 (64.3%) were treated for
      claudication (34 aortoiliac occlusive disease and 20 infrainguinal disease), and
      30 (35.7%) were treated for critical limb ischemia (11 aortoiliac occlusive
      disease and 19 infrainguinal disease). One-year results for the 54 patients with
      claudication were as follows: primary patency, 78.5%; limb salvage, 100%;
      amputation-free survival, 96.3%; survival, 96.3%; maintenance of ambulation
      status, 100%; and maintenance of independence, 100%. There was statistical
      improvement in all physical function categories, including physical function
      (29.4 +/- 8.9 vs 37.1 +/- 11.3; P < .0001), role-physical (32.5 +/- 11.3 vs 39.5
      +/- 13.0; P = .0001), bodily pain (35.8 +/- 8.5 vs 42.9 +/- 10.9; P < .0001), and
      aggregate physical scoring (31.1 +/- 9.7 vs 38.1 +/- 11.5; P < .0001). One-year
      results for the 30 patients with critical limb ischemia were as follows: primary
      patency, 35.2%; limb salvage, 77.2%; amputation-free survival, 50.0%; survival,
      60.0%; maintenance of ambulation status, 75.8%; and maintenance of independence,
      92.8%. There was statistical improvement in bodily pain resolution (35.3 +/- 12.0
      vs 46.6 +/- 12.0; P = .0009). Cox models with hazard ratios (HRs) revealed that
      presentation was a significant predictor for outcomes of primary patency (HR,
      4.2; P= .0002), secondary patency (HR, 6.0; P < .0001), limb salvage (HR, 20.2; P
      = .0047), survival (HR, 10.9; P = .0002), and amputation-free survival (HR, 11.2;
      P < .0001). Conversely, the level of disease was predictive of outcome only for
      primary patency (HR, 1.8; P = .00289). CONCLUSIONS: Despite inferior
      reconstruction patency rates when compared with the historical results of open
      bypass, PTA provides excellent functional outcomes with good patient
      satisfaction, especially for treating claudication. These findings support a more
      liberal use of PTA intervention for patients with vasculogenic claudication.

PMID- 16814977
TI  - Painted into a corner: unexpected complications in treating a Jehovah's Witness.

PMID- 16814978
TI  - Modern concepts of acute and chronic pain management.
AB  - Both, acute and chronic pain should be treated using appropriate pain management
      as they may cause several negative reactions and jeopardise the health or at
      least the quality of life of the patients. Nowadays there are many analgesics and
      treatment tools available to provide sufficient pain relief for almost all
      patients. Unfortunately there are still patients suffering from pain due to
      inadequate or/and inconsequent pain therapy.

PMID- 16814979
TI  - Prevention of cisplatin-induced kidney epithelial cell apoptosis with a Cu
      superoxide dismutase-mimetic [copper2II(3,5
      ditertiarybutylsalicylate)4(ethanol)4].
AB  - Copper(2)(II)(3,5-ditertiarybutylsalicylate)(4)(ethanol)(4), Cu(2)(II)(3,5
      DTBS)(4)(Eth)(4), was synthesized and characterized for evaluation as an anti
      apoptotic superoxide dismutase (SOD)-mimetic in an in vitro 50 microM cis
      diamminedichloroplatinum(II), [Pt(II)(NH(3))(2)(Cl)(2)]-treated kidney proximal
      tubule epithelial cell (LLC-PK) preparation. Synthesized Cu(2)(II)(3,5
      DTBS)(4)(Eth)(4) was characterized by elemental analysis, FTIR spectrophotometry,
      and X-ray crystallography. The IC(50) for SOD-mimetic reactivity of Cu(2)(II)(3,5
      DTBS)(4)(Eth)(4), determined with the xanthine/xanthine oxidase/nitroblue
      tetrazolium (NBT) system, was found to be 2.69 microM for the binuclear chelate.
      Pretreatment of LLC-PK cells with 20 microM Cu(2)(II)(3,5-DTBS)(4)(Eth)(4)
      prevented 50 microM Pt(II)(NH(3))(2)(Cl)(2)-induced and superoxide-mediated
      apoptosis. This SOD-mimetic significantly suppressed Pt(II)(NH(3))(2)(Cl)(2)
      induced translocation of pro-apoptotic Bax from the cytosol to the inner
      mitochondrial membrane, prevented Pt(II)(NH(3))(2)(Cl)(2)-induced release of
      cytochrome c from the inner mitochondrial membrane and the appearance of
      cytochrome c in the cytosol, and prevented conversion of procaspase-3 to active
      caspase-3. Cu(2)(II)(3,5-DTBS)(4)(Eth)(4) treatment inhibited
      Pt(II)(NH(3))(2)(Cl)(2)-mediated tubular cell injury by preventing activation of
      cellular mechanisms that lead to proximal tubule kidney cell death. Based on
      these observations, Pt(II)(NH(3))(2)(Cl)(2)- induced O(2)(-)-mediated apoptosis
      can be mechanistically overcome with a small molecular mass SOD-mimetic,
      Cu(2)(II)(3,5-DTBS)(4)(Eth)(4). Prior treatment of patients who are to undergo
      treatment with Pt(II)(NH(3))(2)(Cl)(2) for their neoplastic disease with
      Cu(2)(II)(3,5-DTBS)(4)(Eth)(4) may be beneficial to these patients.

PMID- 16814980
TI  - Evaluating elements of executive functioning as predictors of instrumental
      activities of daily living (IADLs).
AB  - OBJECTIVE: Executive functioning has been repeatedly linked to the integrity of
      instrumental activities of daily living (IADL). The present study examined the
      association of multiple executive functioning elements (i.e., working memory,
      generation, inhibition, planning, and sequencing) to IADLs among an older adult
      cohort at risk for future cognitive and functional decline. METHODS: Seventy-two
      participants with prevalent but stable cardiovascular disease completed a
      neuropsychological protocol assessing multiple elements of executive functioning,
      including COWA, PASAT, DKEFS Color-Word Interference Test, DKEFS Trail-Making
      Test, DKEFS Tower Test, and Ruff Figural Fluency Test. Reliable informants
      completed a measure of IADLs. RESULTS: Stepwise logistic regression selected a
      model involving a single significant predictor, a measure of inhibition (i.e.,
      DKEFS Color-Word Interference Test), which had a significant regression
      coefficient. Subsequent correlation analyses confirmed an association between the
      inhibition measure and multiple IADL items. Inter-item comparisons among the
      IADLs revealed significant differences, such that telephone use and laundry were
      significantly more intact than most other IADLs while shopping and housekeeping
      were most compromised. CONCLUSIONS: Our data suggest that inhibition, also known
      as susceptibility to interference, is most strongly related to IADL impairment
      among patients at risk for future cognitive and functional decline.

PMID- 16814981
TI  - The OCI-R: validation of the subscales in a clinical sample.
AB  - The psychometric properties of the Obsessive-Compulsive Inventory-Revised (OCI-R)
      subscales have not been validated in a clinical sample of individuals diagnosed
      with obsessive-compulsive disorder (OCD). Data were collected on 186 patients
      diagnosed with OCD and 17 patients diagnosed with generalized anxiety disorder
      (GAD) using the OCI-R and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS).
      Confirmatory factor analysis revealed an acceptable factor structure. Patients
      with a given primary symptom subtype were elevated on the corresponding subscale
      of the OCI-R compared to other OCD patients and patients with GAD. In addition,
      patients who acknowledged that symptom subtype as present but not primary on the
      Y-BOCS had elevated OCI-R scores on that scale compared to patients who did not
      endorse that symptom subtype and patients with GAD. Results indicate that the
      subscales of the OCI-R are valid measures of six symptom subtypes of OCD. The OCI
      R is a psychometrically sound, brief instrument. The current data combined with
      previous efforts suggest that it is appropriate for clinical and non-clinical
      populations, and for clinical and research purposes. Further research should
      examine the sensitivity of the specific subscales to treatment effects, and the
      potential for adding more items to account for other symptom domains of OCD.

PMID- 16814982
TI  - Matching analysis of socially appropriate and destructive behavior in
      developmental disabilities.
AB  - This study examined socially appropriate and destructive behavior in
      unconstrained natural environments using a matching law analysis (MLA) of real
      time observational data. The participants were two school-age children and one
      adult with mild to moderate cognitive disabilities. Event lagged sequential
      analysis (SQA) provided the obtained rates of staff attention to socially
      appropriate and inappropriate behaviors, which were then used in the matching law
      equations. For one participant the matching analysis showed a high (72%) variance
      accounted-for (VAF) in behavior allocation in response to attention. For a second
      participant, matching analysis conducted on behavior allocation in response to
      staff attention showed lower (50%) VAF by staff attention. In the third case, the
      MLA also showed high (94%) VAF by attention. Suggestions for future extensions of
      matching analysis to clinically significant behavior and the limitations of the
      MLA for evaluating functional relationships in natural environments are
      discussed.

PMID- 16814983
TI  - A social recognition test for female mice reveals behavioral effects of
      developmental chlorpyrifos exposure.
AB  - CD-1 mice were exposed to the organophosphate pesticide chlorpyrifos (CPF) both
      prenatally (gestational days 15-18; doses 0, 3 or 6 mg/kg) and postnatally
      (postnatal days 11-14, doses 0, 1 or 3 mg/kg). When four-month-olds, females
      underwent a social recognition test in which ultrasound vocalizations (USVs) and
      social investigation behavior emitted by a resident female in the presence of a
      female partner were measured during two subsequent 3 min sessions (interval
      between the two sessions 45 min). Throughout the social recognition test a marked
      increase in USVs was found in females prenatally treated with the highest CPF
      dose; USV increase was also paralleled by a selective increase in frequency and
      not in duration of social investigation. These results confirm that developmental
      exposure to CPF induces long-lasting alterations in the social behavior
      repertoire of the mouse, thus extending our previous observations on the effects
      of postnatal CPF on male agonistic behavior to the female sex. They also suggest
      that social recognition can be easily and rapidly assessed in the female mouse
      making it possible to evaluate, primarily by means of USV emission, even subtle
      alteration of social behavioral patterns dissociated from cognitive components of
      individual recognition.

PMID- 16814984
TI  - Postprandial serum triacylglycerols and oxidative stress in mice after
      consumption of fish oil, soy oil or olive oil: possible role for paraoxonase-1
      triacylglycerol lipase-like activity.
AB  - OBJECTIVE: Postprandial triacylglycerols and oxidative stress responses are
      influenced by the type of fat consumed. We investigated the effect of individual
      unsaturated fatty acids or oils (fish, soy, or olive) on postprandial
      triglyceridemia response in association with serum resistance to oxidation and
      paraoxonase-1 (PON1) activity. METHODS: Balb/C mice were supplemented with
      phosphate buffered saline (control), docosahexaenoic acid (omega-3), linoleic
      acid (omega-6), or oleic acid (omega-9; 500 microg/300 microL of phosphate
      buffered saline) and with fish, soy, or olive oil (300 microL); blood samples
      were collected 2 h after feeding. RESULTS: Serum triacylglycerol and oxidative
      stress responses increased after intake of all unsaturated fatty acids and oil
      supplements. However, ingestion of fish oil or its major fatty acid,
      docosahexaenoic acid, induced the most remarkable increase in postprandial serum
      triacylglycerols and in the susceptibility of serum to in vitro oxidation. Serum
      PON1 activity was decreased by 24% after fish oil ingestion. The increase in
      postprandial serum susceptibility to oxidation was lower after soy oil
      supplementation to PON1-transgenic mice in comparison with Balb/C mice, showing
      that PON1 attenuates the postprandial serum oxidative response. In parallel, in
      PON1-transgenic mice, a decreased postprandial triacylglycerol response was
      noted, suggesting PON1 involvement in triacylglycerol metabolism. PON1 exhibited
      a triacylglycerol lipase-like activity on chylomicrons. CONCLUSION: PON1
      attenuates the postprandial oxidative stress response, and this could have
      resulted from PON1 lipase-like activity on chylomicron triacylglycerols.

PMID- 16814985
TI  - Effects of dietary genistein on hepatic lipid metabolism and mitochondrial
      function in mice fed high-fat diets.
AB  - OBJECTIVE: Genistein has been suggested to prevent insulin resistance and its
      related diseases. We investigated the effects of dietary genistein at different
      levels on hepatic lipid levels and mitochondrial functions in mice fed high-fat
      diets. METHODS: C57BL/6J mice were randomly divided into four groups and fed a
      high-fat diet containing genistein at levels of 0%, 0.1%, 0.2%, and 0.4% (HF, HF
      + 0.1G, HF + 0.2G, and HF + 0.4G) for 12 wk. We measured lipid levels in the
      blood and liver. We also observed messenger RNA (mRNA) expression of genes
      encoding proteins related to lipid and energy metabolism and antioxidant defense
      system and mitochondrial enzyme activities in the liver. RESULTS: The induction
      of fatty liver by HF was substantially decreased in the HF + 0.2G and HF + 0.4G
      groups. Peroxisome proliferator-activated receptorgamma coactivator mRNA was
      increased by HF + 0.4G. Although genistein did not affect peroxisomal acyl-CoA
      oxidase mRNA expression, it increased medium-chain acyl-CoA dehydrogenase mRNA
      expression in a dose-dependent manner and HF + 0.2G increased uncoupling protein
      2 mRNA expression two-fold relative to HF mice. Genistein decreased
      malondialdehyde levels and increased glutathione levels in liver homogenates,
      regardless of dose. The HF + 0.1G diet increased mitochondrial glutathione
      peroxidase activity and mitochondrial succinate dehydrogenase activity.
      CONCLUSIONS: Although genistein at higher levels decreased hepatic fat
      accumulation possibly by increasing fatty acid oxidation and uncoupling protein,
      low-dose genistein increased mitochondrial enzyme activities in mice with fatty
      liver and obesity induced by high-fat diets.

PMID- 16814986
TI  - Deficit in schizophrenia to recruit the striatum in implicit learning: a
      functional magnetic resonance imaging investigation.
AB  - In schizophrenia, explicit learning deficits have been well established although
      it is less clear whether these patients have deficits in implicit learning (IL).
      IL is thought to depend on intact striatal functioning. This study examined the
      hypothesis that schizophrenia patients show deficient recruitment of striatal
      activation during an IL paradigm, relative to performance-matched healthy
      comparison subjects. Ten subjects with schizophrenia on atypical antipsychotic
      medication and 10 age, gender, education, and performance matched healthy
      comparison subjects underwent fMRI while performing an IL task. On the basis of
      whole-brain and striatal region-of-interest analyses, we found a relative lack of
      striatal activation in schizophrenia patients. This result is consistent with
      convergent evidence of striatal dysfunction in schizophrenia.

PMID- 16814987
TI  - Detection of Listeria monocytogenes in food using a combined enrichment/real-time
      PCR method targeting the prfA gene.
AB  - A combined enrichment/real-time PCR method for the detection of Listeria
      monocytogenes is presented. The method is based on a conventional PCR assay
      targeting the prfA gene, which has been validated and suggested as an
      international standard PCR method for identifying L. monocytogenes in food. This
      real-time PCR assay includes an internal amplification control. Inclusivity and
      exclusivity were 100% each when testing 100 L. monocytogenes isolates, 30
      Listeria spp. isolates other than L. monocytogenes, and 29 non-Listeria isolates.
      The theoretical detection limit was one copy of the target gene per PCR reaction
      and the practical detection limit was about 5 copies per PCR. Using the combined
      enrichment/real-time PCR method, 7.5 CFU/25 ml of artificially contaminated raw
      milk, and 9, 1, and 1 CFU/15 g of artificially contaminated salmon, pate, and
      green-veined cheese, respectively, were detected. When analyzing 76 naturally
      contaminated food samples of various types and comparing the results with the ISO
      11290-1 standard method, the relative accuracy was 96%, the relative specificity
      100%, and the relative sensitivity, 76.9%.

PMID- 16814988
TI  - An in vitro study of adherence of coagulase-negative staphylococci to bone chip
      columns.
AB  - Coagulase-negative staphylococci (CNS) have become a dominant cause of bone
      infections and their adherence to the infected bones is a prerequisite for the
      initiation of these infections. In the present study we investigated and compared
      the adherence of CNS bacteria to human, chicken and rabbit bones. The study was
      performed using columns made of bone powder from the three different sources, and
      measurement of the extent of adhesion to bones of CNS bacteria as an in vitro
      model which is based on particles of matrix that are closely related to the
      natural matrix. The adhesion to rabbit bone was relatively high, while adhesion
      to both human and chicken bone columns was lower and almost identical.
      Pretreatment of the CNS bacteria with sodium periodate, beta-galactosidase or
      proteinase K significantly inhibited by 50-60% the adhesion to human bones.
      Pretreatment of CNS bacteria with subinhibitory concentrations of vancomycin or
      tunicamycin increased their adherence to human bones several-fold. When the bones
      were pretreated with vancomycin a considerable increase in the adhesion rate of
      the bacteria to human and chicken bones was seen. A smaller increase in adherence
      was observed after pretreatment of human bones with the antibiotic tunicamycin.
      Salicylic acid or benzalkonium chloride (BZC) also resulted in an increase in
      adhesion to these pretreated bones. From the results obtained it seems that
      pretreatment of the CNS bacteria with certain reagents exposes adhesins on the
      surface of the CNS bacteria. On the other hand, pretreatment of the bones with
      other reagents may enable a better exposure of receptors located on the bone
      cells and, as a consequence, may improve the adhesion of the CNS bacteria to the
      treated bones.

PMID- 16814989
TI  - Exposure to sulfide causes populations shifts in sulfate-reducing consortia.
AB  - The shift in the community structure of a mixed culture of sulfate-reducing
      bacteria (SRB) at 0.5, 0.75, 1, and 1.5 kg m(-3) sulfide loadings was
      investigated in an anaerobic continuous bioreactor used for treatment of sulfate
      containing wastewater by fluorescence in situ hybridization (FISH), using SRB
      species-specific and group-specific 16S rRNA-targeting probes. Hybridization
      analysis using these 16S rRNA-targeted oligonucleotide probes revealed that
      sulfide was toxic for Desulfonema, Desulfobulbus spp. and the Desulfobacteriaceae
      group, although it was not toxic for Desulfobacter, Desulfotomaculum,
      Desulfobacterium spp. or the Desulfovibrionaceae group. On the other hand, only a
      high concentration of sulfide of 1.5 kg m(-3) was found to be toxic for the
      Desulfococcus group in the bioreactor. When the sulfide in the feed was 1.00 kg
      m(-3) the sulfate-reducing capacity of the system decreased, and this decrease
      was more pronounced when the inlet sulfide was further increased to 1.5 kg m(-3).

PMID- 16814990
TI  - A novel role for protein-tyrosine kinase Etk from Escherichia coli K-12 related
      to polymyxin resistance.
AB  - The role of protein-tyrosine kinases in bacterial polymyxin resistance was
      assessed by both genetic and biochemical approaches. Each of the two genes, wzc
      and etk, encoding protein-tyrosine kinases in Escherichia coli, was knocked out
      by using the PCR-based method of one-step inactivation of chromosomal genes, and
      the corresponding mutant strain was assayed in each case for resistance to
      different concentrations of polymyxin B by measuring the percentage of surviving
      cells. The resistance of a double knock-out wzc-etk-mutant was also analyzed and
      complementation experiments were performed by checking the effect of plasmid
      vectors expressing either Wzc or Etk. Our results concurred in showing that
      protein-kinase Wzc is not essential for polymyxin resistance, whereas protein
      kinase Etk appears to play a key role in such antibiotic resistance. This newly
      found specific function of Etk reinforces the concept that protein-tyrosine
      kinases are involved in distinct facets of bacterial physiology.

PMID- 16814991
TI  - Enhanced culture of Borrelia garinii and Borrelia afzelii strains on a solid BSK
      based medium in anaerobic conditions.
AB  - The growth of 29 human strains from the three main pathogenic species of Borrelia
      burgdorferi sensu lato on a solid BSK-based medium was compared in two culture
      atmospheres: 3% CO(2) air and anaerobiosis. All strains grew under anaerobic
      conditions, whereas only 13 strains were able to grow in aerobiosis with 3% CO(2)
      (P<0.001). In the latter condition, 75% of the B. burgdorferi sensu stricto
      strains grew versus 33% of the B. garinii and B. afzelii strains. These data
      suggest that, especially for B. garinii and B. afzelii species, anaerobic
      conditions enhance growth yield and speed of low-passage Borrelia strains.

PMID- 16814992
TI  - Control of ribosome turnover during growth of the haloalkaliphilic archaeon
      Natronococcus occultus.
AB  - The metabolism of ribosomes during growth of the haloalkaliphilic archaeon
      Natronococcus occultus was examined. The ribosome content was higher during
      exponential growth and diminished to 35% of the maximum in the stationary stage.
      The incorporation of H3-orotic acid and C14-uracil into rRNA was higher during
      exponential growth. After that, it decreased to 39% of the maximum in the
      stationary stage. The labeling of non-ribosomal RNA took place almost exclusively
      in the exponential stage. From loss of radioactivity, the half-life of rRNA was
      11.43, 14.85, 5.28 and 7.14 h during the initial, exponential, late exponential
      and stationary growth stages, respectively. These results suggested that
      increased synthesis combined with diminished degradation were responsible for the
      high ribosome content displayed by Ncc. occultus during exponential growth. In
      contrast, diminished synthesis together with increased degradation provoked its
      posterior loss.

PMID- 16814993
TI  - Set shifting deficits in melancholic vs. non-melancholic depression: preliminary
      findings.
AB  - Twenty-two patients with major depressive disorder, 11 of them with melancholic
      features, and 11 controls were investigated with CANTAB subtests focusing in
      visual memory/learning and executive functions. Melancholic patients performed
      worse than the other groups in all tasks and manifested a significant impairment
      in set shifting. The results are discussed in association with prefrontal
      dysfunction.

PMID- 16814994
TI  - Preparation of insulin-loaded PLA/PLGA microcapsules by a novel membrane
      emulsification method and its release in vitro.
AB  - Uniform-sized biodegradable PLA/PLGA microcapsules loading recombinant human
      insulin (rhI) were successfully prepared by combining a Shirasu Porous Glass
      (SPG) membrane emulsification technique and a double emulsion-evaporation method.
      An aqueous phase containing rhI was used as the inner water phase (w1), and
      PLA/PLGA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane
      (DCM) and toluene, which was used as the oil phase (o). These two solutions were
      emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion
      was permeated through the uniform pores of a SPG membrane into an outer water
      phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. The
      solid polymer microcapsules were obtained by simply evaporating solvent from
      droplets. Various factors of the preparation process influencing the drug
      encapsulation efficiency and the drug cumulative release were investigated
      systemically. The results indicated that the drug encapsulation efficiency and
      the cumulative release were affected by the PLA/PLGA ratio, NaCl concentration in
      outer water phase, the inner water phase volume, rhI-loading amount, pH-value in
      outer water phase and the size of microcapsules. By optimizing the preparation
      process, the drug encapsulation efficiency was high up to 91.82%. The unique
      advantage of preparing drug-loaded microcapsules by membrane emulsification
      technique is that the size of microcapsules can be controlled accurately, and
      thus the drug cumulative release profile can be adjusted just by changing the
      size of microcapsules. Moreover, much higher encapsulation efficiency can be
      obtained when compared with the conventional mechanical stirring method.

PMID- 16814995
TI  - Some advances in plant stress physiology and their implications in the systems
      biology era.
AB  - The study for biointerfaces at different scales in the past years has pricked up
      the march of biological sciences, in which biomembrane concept and its
      characteristics, receptor proteins, ion channel proteins, LEA proteins, calcium
      and newly recognized second messengers, ROS, MAPKs and their related sensors and
      new genes in osmoregulation, signal transduction, and other aspects have been
      understood fully, widening area of understanding the extensive interactions from
      biosystem and biointerfaces. The related discipline, plant stress physiology,
      especially, crop stress physiology has gained much attention world widely, the
      important reason of which is from the reducing quality of global ecoenvironment
      and decreasing food supply. This short review will place a stress on the recent
      progresses in plant stress physiology, combined with the new results from our
      State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau.

PMID- 16814996
TI  - Mixing of perfluorooctanesulfonic acid (PFOS) potassium salt with dipalmitoyl
      phosphatidylcholine (DPPC).
AB  - Perfluorooctane-1-sulfonic acid (PFOS) is emerging as an important persistent
      environmental pollutant. To gain insight into the interaction of PFOS with
      biological systems, the mixing behavior of dipalmitoylphosphatidylcholine (DPPC)
      with PFOS was studied using differential scanning calorimetry (DSC) and
      fluorescence anisotropy measurements. In the DSC experiments the onset
      temperature of the DPPC pretransition (Tp) decreased with increasing PFOS
      concentration, disappearing at XDPPC < or = 0.97. The main DPPC phase transition
      temperature showed a depression and peak broadening with increasing mole fraction
      of PFOS in both the DSC and the fluorescence anisotropy studies. From the melting
      point depression in the fluorescence anisotropy studies, which was observed at a
      concentration as low as 10 mg/L, an apparent partition coefficient of K = 5.7 x
      10(4) (mole fraction basis) was calculated. These results suggest that PFOS has a
      high tendency to partition into lipid bilayers. These direct PFOS-DPPC
      interactions are one possible mechanism by which PFOS may contribute to adverse
      effects, for example neonatal mortality, in laboratory studies and possibly in
      humans.

PMID- 16814997
TI  - Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant
      containing soya phosphatidylcholine.
AB  - Microemulsions (ME) containing soya phosphatidylcholine
      (SPC)/polyoxyethylenglycerol trihydroxystearate 40 (EU)/sodium oleate (SO) as
      surfactant cholesterol (CHO) as oil phase and aqueous buffer were studied. Pseudo
      ternary phase diagrams of the investigated systems were obtained at constant
      SPC/EU/SO weight ratio 3.5:3.5:3.0 by titration, in order to characterize the
      proportions between the components to form clear systems. The dynamic light
      scattering results showed that the size of the oil droplets decreases
      significantly with the ratio of surfactant/oil phase added to system. Depending
      on the composition ME system could exhibit a thixotropic behavior. The apparent
      viscosity increased 25- and 13-folds with cholesterol concentration for drug-free
      and drug-load ME, respectively. It was also verified that the octanol/aqueous
      buffer partition coefficient (KO/B) of doxorubicin (DOX) was pH dependent
      increasing abruptly above pH 6.0. It was possible to incorporate 2.24 mg/ml of
      DOX into ME. The incorporation of DOX in the ME systems increased the droplets
      size for all surfactant concentrations used in the system. The results suggest
      that DOX interacts with the microstructure of the ME at the studied pH increasing
      significantly the drug solubility. It was possible to conclude that the
      investigated ME can be a very promising vehicle as drug-carrier for
      administration of doxorubicin.

PMID- 16814998
TI  - Preparation of latex reagents combined with IgM and its F(ab')2 fragment from
      commercial ABO blood grouping reagent.
AB  - To achieve a rapid assay for ABO blood grouping using a latex reagent, two latex
      reagents were produced, one of which combined with mouse monoclonal
      immunoglobulin M (IgM) isolated from commercial ABO blood grouping reagent, and
      the other of which combined with its F(ab')2 fragment prepared by cold pepsin
      digestion. The latex reagent adsorbing the F(ab')2 fragment was able to detect
      the 1000-fold diluted saliva and provided much better sensitivity than that of
      IgM. This suggests that the difference in sensitivity between the two latex
      reagents is responsible for adsorption orientation of the antigen site on the
      latex particles. The new assay successfully completed the ABO blood grouping of
      cigarette ends within 30 min.

PMID- 16814999
TI  - Simple coacervates of zein to encapsulate Gitoxin.
AB  - This work reports the use of simple coacervates of the hydrophobic protein zein
      to encapsulate Gitoxin, a cardiotonic glycoside. The microspheres obtained using
      ethanol, methanol, iso-propyl alcohol were characterized using viscosity index,
      scanning electron microscopy (SEM) and laser light scattering particle analyzer.
      Scanning electron micrographs indicated that the zein film was made of
      microspheres with diameter in the 1-1.5 microm range, which could be controlled.
      Sizes of Gitoxin-loaded zein microspheres changed little before and after release
      of the drug because of conglutination among zein microspheres. Release of Gitoxin
      from zein microspheres, were performed in vitro to investigate the mechanism of
      model drug release. The results show that the zein microspheres obtained using
      ethanol are best suited for use as a sustained-release form of Gitoxin. The
      microspheres may also be useful in drug targeting system since the diameter of
      the microspheres is appropriate for phagocytosis by macrophages. Both zein film
      and Gitoxin-loaded zein microsphere film were effective in suppressing platelet
      adhesion.

PMID- 16815000
TI  - Kinetics of yeast detachment from controlled stainless steel surfaces.
AB  - Using a radial flow chamber, we study Saccharomyces cerevisiae kinetics of
      detachment from stainless steel substrates. Samples of similar surface chemistry,
      but with different surface topologies are compared: mirror polished and electro
      chemically etched. Different grain sizes (20, 40 and 100 microm) and different
      etching depths (100-650 nm) are tested. Cells are removed from the substrate
      according to a first-order kinetics defining two macroscopic parameters that
      depend on the applied stress: the detachment efficiency and the detachment rate
      constant. Whatever the surface topology, detachment occurs above a threshold and
      its rate is strongly stimulated by the applied stress. The detachment efficiency
      is characterized by the shear stress at which half of the cells detach and is
      independent of surface topology. In contrast, detachment is faster from etched
      than mirror polished surfaces. Finally, we also show the preferential adhesion of
      yeast cells to grains of < 001 > crystallographic orientation with respect to the
      surface.

PMID- 16815001
TI  - Formulation of poorly water-soluble drugs for oral administration:
      physicochemical and physiological issues and the lipid formulation classification
      system.
AB  - Poorly water-soluble drug candidates often emerge from contemporary drug
      discovery programs, and present formulators with considerable technical
      challenges. The absorption of such compounds when presented in the crystalline
      state to the gastrointestinal tract is typically dissolution rate-limited, and
      the drugs are typically BCS class II or class IV compounds. Class IV compounds,
      which have low membrane permeability as well as poor aqueous solubility, are
      often poor candidates for development, unless the dose is expected to be low. The
      rate and extent of absorption of class II compounds is highly dependent on the
      performance of the formulated product. These drugs can be successfully formulated
      for oral administration, but care needs to be taken with formulation design to
      ensure consistent bioavailability. Essentially the options available involve
      either reduction of particle size (of crystalline drug) or formulation of the
      drug in solution, as an amorphous system or lipid formulation. The performance of
      amorphous or lipid formulations is dependent on their interaction with the
      contents of the gastrointestinal tract, therefore, a formulation exercise should
      involve the use of techniques which can predict the influence of gut physiology.
      A major consideration is the fate of metastable supersaturated solutions of drug,
      which are formed typically after dispersion of the formulation and its exposure
      to gastrointestinal digestion. A better understanding of the factors which affect
      drug crystallization is required, and the introduction of standardised predictive
      in vitro tests would be valuable. Although many bioavailability studies have been
      performed with poorly water-soluble drugs, thus far this research field has
      lacked a systematic approach. The use of a lipid formulation classification
      system combined with appropriate in vitro tests will help to establish a database
      for in vitro-in vivo correlation studies.

PMID- 16815003
TI  - A novel alcohol dehydrogenase biosensor based on solid-state electrogenerated
      chemiluminescence by assembling dehydrogenase to Ru(bpy)(3)2+-Au nanoparticles
      aggregates.
AB  - Based on electrogenerated chemiluminescence (ECL), a novel method for fabrication
      of alcohol dehydrogenase (ADH) biosensor by self-assembling ADH to Ru(bpy)(3)(2+)
      AuNPs aggregates (Ru-AuNPs) on indium tin oxide (ITO) electrode surface has been
      developed. Positively charged Ru(bpy)(3)(2+) could be immobilized stably on the
      electrode surface with negatively charged AuNPs in the form of aggregate via
      electrostatic interaction. On the other hand, AuNPs are favourable candidates for
      the immobilization of enzymes because amine groups and cysteine residues in the
      enzymes are known to bind strongly with AuNPs. Moreover, AuNPs can act as tiny
      conduction centers to facilitate the transfer of electrons. Such biosensor
      combined enzymatic selectivity with the sensitivity of ECL detection for
      quantification of enzyme substrate, and it displayed wide linear range, high
      sensitivity and good stability.

PMID- 16815004
TI  - Photosynthetic reaction center functionalized nano-composite films: effective
      strategies for probing and exploiting the photo-induced electron transfer of
      photosensitive membrane protein.
AB  - Photosynthetic reaction center (RC), a robust transmembrane pigment-protein
      complex, works as the crucial component participating the primary event of the
      photo-electrochemical conversion in bacteria. Sparked by the high photo-induced
      charge separation yield (ca. 100%) of RC, great interests have been aroused to
      fabricate versatile RC-functionalized nano-composite films for exploring the
      initial photosynthetic electron transfer (ET) of RC, and thus exploiting well
      designed bio-photoelectric converters. In this review, we classify and summarize
      the current status about the concepts and methods of constructing RC-immobilized
      nano-composite films or devices for probing the photo-induced ET, and applying to
      novel bioelectronics if it is possible.

PMID- 16815005
TI  - A molecular beacon DNA microarray system for rapid detection of E. coli O157:H7
      that eliminates the risk of a false negative signal.
AB  - A DNA hybridization based optical detection platform for the detection of
      foodborne pathogens has been developed with virtually zero probability of the
      false negative signal. This portable, low-cost and real-time assaying detection
      platform utilizes the color changing molecular beacon as a probe for the optical
      detection of the target sequence. The computer-controlled detection platform
      exploits the target hybridization induced change of fluorescence color due to the
      Forster (fluorescence) resonance energy transfer (FRET) between a pair of
      spectrally shifted fluorophores conjugated to the opposite ends of a beacon
      (oligonucleotide probe). Unlike the traditional fluorophore-quencher beacon
      design, the presence of two fluorescence molecules allows to actively visualize
      both hybridized and unhybridized states of the beacon. This eliminates false
      negative signal detection characteristic for the fluorophore-quencher beacon
      where bleaching of the fluorophore or washout of a beacon is indistinguishable
      from the absence of the target DNA sequence. In perspective, the two-color design
      allows also to quantify the concentration of the target DNA in a sample down to <
      =1 ng/microl. The new design is suitable for simultaneous reliable detection of
      hundreds of DNA target sequences in one test run using a series of beacons
      immobilized on a single substrate in a spatial format.

PMID- 16815006
TI  - The treatment of melanoma with an emphasis on immunotherapeutic strategies.
AB  - Melanoma continues to be one of the most difficult to treat of all solid tumors.
      Many new advances have been made in the surgical management of melanoma,
      including new guidelines for margins of excision, as well as sentinel node biopsy
      for the diagnosis of lymph node micrometastases. The search continues for an
      effective adjuvant melanoma treatment that can prevent local and distant
      recurrences. Melanoma is one of the most immunogenic of all tumors, and several
      clinical trials testing the immunotherapy of melanoma have been conducted,
      including trials in interferon, interleukin-2, and melanoma vaccines. Here we
      discuss many of the recent clinical trials in the surgical management of
      melanoma, in addition to the advances that have been made in the field of
      immunotherapy. A new second-generation melanoma vaccine, DC-MelVac (patent #
      11221/5), has recently been granted FDA approval for Phase I clinical trials and
      will be introduced in this review.

PMID- 16815007
TI  - Dye adsorption by prehydrolysed beech sawdust in batch and fixed-bed systems.
AB  - The batch and column kinetics of methylene blue and red basic 22 adsorption on
      mild acid-hydrolysed beech sawdust were investigated, using untreated beech
      sawdust as control, in order to explore its potential use as a low cost adsorbent
      for wastewater dye removal. The adsorption capacities, estimated according to
      Freundlich's model, and the adsorption capacity coefficient values, determined
      using the Bohart and Adams' bed depth service model, indicated that prehydrolysis
      enhances the adsorption properties of the original material. This enhancement can
      possibly be attributed to (a) the removal of the hemicelluloses during sulphuric
      acid treatment, resulting in the 'opening' of the lignocellulosic matrix's
      structure and the increasing of the BET surface area and (b) the activation of
      the material's surface owing to an increase in the number of dye binding sites.

PMID- 16815008
TI  - Biotreatment of waste gas containing pyridine in a biofilter.
AB  - Industrial waste gas emissions containing pyridine are generated from pyridine
      manufacturing industries, and in industrial operations where pyridine is used as
      a solvent, as an intermediate for synthesis and as a catalyst for a variety of
      applications. Pyridine has unpleasant fishy odor with an odor index of 2390 and
      waste gaseous emissions containing pyridine require proper treatment prior to
      discharge. A biofilter, packed with compost and wood chips and inoculated with
      Pseudomonas pseudoalcaligenes-KPN for enrichment of pyridine-degrading
      microorganisms, was operated on a continuous feed basis for a period of more than
      2 years. The results indicate that the biofilter medium with optimal moisture
      content of 68% and an effective bed retention time (EBRT) of 28.50s could degrade
      pyridine effectively (>99%) at a loading of 434 g pyridine m(-3)h(-1). The
      treated waste gas was also found to be free from pyridine odor.

PMID- 16815009
TI  - Agronomic effectiveness of biofertilizers with phosphate rock, sulphur and
      Acidithiobacillus for yam bean grown on a Brazilian tableland acidic soil.
AB  - Phosphate rocks have low available P and soluble P fertilizers have been
      preferably used in plant crop production, although economic and effective P
      sources are needed. Experiments were carried out on a Brazilian Typic Fragiudult
      soil with low available P to evaluate the agronomic effectiveness of phosphate
      rock (PR) compared with soluble phosphate fertilizer. Yam bean (Pachyrhizus
      erosus) inoculated with rhizobia (strains NFB 747 and NFB 748) or not inoculated
      was the test crop. Biofertilizers were produced in field furrows by mixing
      phosphate rock (PR) and sulphur inoculated with Acidithiobacillus (S+Ac) in
      different rates (50, 100, 150 and 200 g S kg(-1) PR), with 60 days of incubation.
      Treatments were carried out with PR; biofertilizers B(50), B(100), B(150),
      B(200); triple super phosphate (TSP); B(200) without Acidithiobacillus and a
      control treatment without P application (P(0)). TSP and biofertilizers plus S
      inoculated with Acidithiobacillus increased plant growth. Soil acidity and
      available P increased when biofertilizers B(150) and B(200) were applied. We
      conclude that biofertilizers may be used as P source; however, long term use will
      reduce soil pH and potentially reduce crop growth.

PMID- 16815010
TI  - Regression models of ultimate methane yields of fruits and vegetable solid
      wastes, sorghum and napiergrass on chemical composition.
AB  - Several fractions of fruits and vegetable solid wastes (FVSW), sorghum and
      napiergrass were analyzed for total solids (TS), volatile solids (VS), total
      organic carbon, total kjeldahl nitrogen, total soluble carbohydrate, extractable
      protein, acid-detergent fiber (ADF), lignin, cellulose and ash contents. Their
      ultimate methane yields (B(o)) were determined using the biochemical methane
      potential (BMP) assay. A series of simple and multiple regression models relating
      the B(o) to the various substrate constituents were generated and evaluated using
      computer statistical software, Statistical Package for Social Sciences (SPSS).
      The results of simple regression analyses revealed that, only weak relationship
      existed between the individual components such as carbohydrate, protein, ADF,
      lignin and cellulose versus B(o). A regression of B(o) versus combination of two
      variables as a single independent variable such as carbohydrate/ADF and
      carbohydrate+protein/ADF also showed that the relationship is not strong. Thus it
      does not appear possible to relate the B(o) of FVSW, sorghum and napiergrass with
      single compositional characteristics. The results of multiple regression analyses
      showed promise and the relationship appeared to be good. When ADF and lignin/ADF
      were used as independent variables, the percentage of variation accounted for by
      the model is low for FVSW (r(2)=0.665) and sorghum and napiergrass (r(2)=0.746).
      Addition of nitrogen, ash and total soluble carbohydrate data to the model had a
      significantly higher effect on prediction of B(o) of these wastes with the r(2)
      values ranging from 0.9 to 0.99. More than 90% of variation in B(o) of FVSW could
      be accounted for by the models when the variables carbohydrate, lignin,
      lignin/ADF, nitrogen and ash (r(2)=0.904), carbohydrate, ADF, lignin/ADF,
      nitrogen and ash (r(2)=0.90) and carbohydrate/ADF, lignin/ADF, lignin and ash
      (r(2)=0.901) were used. All the models have low standard error values, which
      indicate the amount of spread is less. Thus, considering only the higher r(2)
      values, six models are proposed for predicting the B(o) based on FVSW data and
      sorghum and napiergrass data. It would be more convenient if B(o) could be
      predicted by analyzing the chemical composition of the substrate rather than
      performing the long-term batch fermentation. To test the validity of the
      regression models, chemical constituents of FVSW that were not included in the
      regression analyses were determined and their experimental B(o) were determined
      by BMP assay. All the six models were used to predict the B(o) from the chemical
      constituents of these FVSW. It was found that most of the predicted values were
      within 20% of the experimental B(o) in models 1, 3 and 6. Since models 3 and 6
      used the same variables namely, total soluble carbohydrate, ADF, lignin/ADF,
      nitrogen and ash, B(o) can be predicted from these five chemical constituents
      which accounts for more than 90% of the variation in B(o) (r(2)>90).

PMID- 16815011
TI  - Composition and larvicidal activity of leaves and stem essential oils of
      Chloroxylon swietenia DC against Aedes aegypti and Anopheles stephensi.
AB  - The laboratory bioassay of the essential oil and the isolated compounds from
      Chloroxylon swietenia against Aedes aegypti and Anopheles stephensi was carried
      out to evaluate the larvicidal activity. LC50 value estimated for A. aegypti and
      An. stephensi were 16.5 and 14.9 microg/ml and 20.2 and 19 microg/ml for leaf and
      stem oils, respectively. The three sesquiterpenes pregeijerene, geijerene and
      germacrene D were isolated and their Larvicidal activity was evaluated.
      Pregeijerene and geijerene were observed for the first time in the volatile
      constituents of C. swietenia, however, leaves contained higher amount of
      geijerene compared to stems.

PMID- 16815012
TI  - Tetrahydrofluorenones with conformationally restricted side chains as selective
      estrogen receptor beta ligands.
AB  - A series of 2-9a bridged tetrahydrofluorenone derivatives were prepared which
      exhibited significant binding affinity for ERbeta and were highly selective.

PMID- 16815013
TI  - Viral immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling in
      cell transformation and cancer.
AB  - Viruses frequently co-opt host cell pathways to enhance their propagation or to
      enable latent infection. Certain receptors expressed by hematopoietic cells have
      immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic
      domains that initiate cellular activation, proliferation and differentiation.
      Some viruses have evolved, or acquired from their host, genes that encode ITAM
      bearing proteins. These ITAM-bearing viral proteins have been implicated in
      cellular transformation in virus-infected hematopoietic cells, typically B cells,
      but also in non-hematopoietic tissues--including endothelial and epithelial
      cells.

PMID- 16815014
TI  - Evidence for an ER to Golgi to chloroplast protein transport pathway.
AB  - Chloroplast protein import is generally believed to occur posttranslationally
      through the interaction of a precursor protein with the Toc and Tic transport
      apparatus in the plastid envelope membranes. The cleavable N-terminal transit
      peptide present on translocated proteins has been considered to be essential and
      sufficient for targeting. This idea was recently challenged when an analysis of
      the chloroplast proteome revealed many proteins without a predicted transit
      peptide. A recent study demonstrates the existence of a novel chloroplast
      targeting pathway, starting with protein entry into the endoplasmic reticulum and
      involving the Golgi apparatus.

PMID- 16815015
TI  - How original is your writing?

PMID- 16815016
TI  - Epidermoid cyst with infiltrative malignant melanoma in the cerebellopontine
      angle.
AB  - We report a patient with an intracranial epidermoid cyst associated with
      malignant melanoma in the cerebellopontine angle. The CT, MRI and
      histopathological findings showed an intracranial epidermoid cyst with an
      adjacent infiltrating melanoma. Immunohistochemical staining of the solid tumour
      was positive for the melanoma marker HMB45 and negative for GFAP and cytokeratin.
      Both CT and MRI were helpful in this patient but the diagnosis could only be made
      on histopathology.

PMID- 16815017
TI  - Diffusion-weighted MRI predicts prognosis in severe hypoglycemic encephalopathy.
AB  - A 20-year-old woman presented unconscious due to hypoglycemia after a self
      administered insulin injection. Diffusion-weighted MRI (DWI), performed 5 days
      after admission, demonstrated heterogeneous high-intensity signal areas in both
      the cortex and subcortex but sparing the motor and sensory centers. On the 11th
      day after admission, she began making incomprehensible verbal sounds, eye opening
      spontaneously and moving her extremities with pyramidal tract signs. Three months
      later, she had aphasia, agnosia and apraxia but a normal gait without pyramidal
      tract signs or ataxia. DWI is thus considered useful to predict the functional
      outcome of patients with severe hypoglycemia.

PMID- 16815018
TI  - Simultaneous microsurgical and endovascular management of multiple cerebral
      aneurysms in acute subarachnoid haemorrhage.
AB  - Most aneurysms can be effectively managed using endovascular coiling or
      microsurgical clipping, but in an acute subarachnoid haemorrhage where there are
      multiple aneurysms identified, a sequential multimodal approach may prove more
      beneficial. This report involves a 31-year-old man who presented with sudden
      onset of severe headache and photophobia. A computed tomography brain scan
      revealed a diffuse grade II subarachnoid haemorrhagic pattern, and four-vessel
      angiography revealed two aneurysms: a right middle cerebral artery bifurcation
      aneurysm measuring 12 x 8 mm and a 4-mm basilar artery aneurysm associated with a
      fenestration at the confluence of the vertebral arteries. It was not possible to
      determine which aneurysm or aneurysms were responsible for the haemorrhage using
      the customary criteria. The patient underwent sequential endovascular coiling of
      the vertebrobasilar aneurysm without delay, followed immediately by microsurgical
      clipping of the right middle cerebral artery aneurysm, under a single
      anaesthetic. The postoperative course was uneventful. This method is a treatment
      option for acute subarachnoid haemorrhage where there are multiple aneurysms. It
      is a logical progression of management that could be employed at any experienced
      neurovascular centre; the employment of a sequential multimodal approach from the
      integration of these techniques is beneficial to the patient because it decreases
      morbidity and mortality.

PMID- 16815019
TI  - Epidural extension of a lumbar vertebral haemangioma.
AB  - Vertebral haemangiomas are relatively common, but those extending into the
      epidural space are rare. A 59-year-old man with severe lower back and right leg
      pain that did not resolve with conservative treatment was seen in an outpatient
      clinic. Magnetic resonance imaging of the lumbar spine identified an L3 vertebral
      corpus lesion with epidural extension. The diagnosis was unclear, so the patient
      underwent surgery. The pathologic diagnosis was capillary haemangioma, so
      angiography-guided embolization was performed postoperatively. Vertebral
      haemangioma must be considered when there is evidence of a vertebral corpus
      lesion with epidural extension on magnetic resonance imaging.

PMID- 16815020
TI  - Extracranial metastases of a glioblastoma multiforme to the pleura, small bowel
      and pancreas.
AB  - Extracranial metastases of glioblastoma multiforme (GBM) are rare and usually
      occur in the context of recurrent intracranial GBM. We present a 39-year-old man
      with histologically confirmed GBM. The patient remained well for nearly 2 years,
      with no signs of recurrent tumour. He then presented with distant recurrence
      within the brain at the same time as developing pneumonia and epigastric pain. A
      computed tomography scan of the patient's abdomen and chest showed several intra
      abdominal masses, including one in the head of the pancreas as well as a separate
      mass at the base of the left lung. A computed tomography-guided biopsy of the
      pancreatic mass demonstrated histological appearances identical to those of the
      original GBM. This unusual case raises the possibility of a link between
      prolonged survival with GBM and the occurrence of extracranial disease.

PMID- 16815021
TI  - Posterior decompression and fusion: dorsal migration of the spinal cord is the
      key!

PMID- 16815022
TI  - Intrasellar cavernous hemangioma.
AB  - Reports of intrasellar cavernous hemangioma are rare. They are usually incidental
      findings at autopsy, or initially mistaken for pituitary adenoma and treated
      accordingly. There are no specific symptoms. Cranial nerve palsy has occasionally
      been reported in patients with cavernous hemangioma, with or without sellar
      extension. However, intrasellar cavernous hemangioma with extension into the
      cavernous sinus resulting in oculomotor palsy has not been reported. We present a
      rare case of intrasellar cavernous hemangioma and discuss the diagnosis and
      management. Total surgical removal is recommended. However, attempts to resect
      the parasellar component of the lesion may be associated with high morbidity.
      Therefore, surgical cranial nerve decompression in the acute stage followed by
      stereotactic radiosurgery for the residual lesion may be an alternative.

PMID- 16815023
TI  - Factors influencing visual and clinical outcome in Nigerian patients with cranial
      meningioma.
AB  - We retrospectively analysed the impact of selected clinicopathological factors on
      visual and clinical outcome in patients with histologically verified cranial
      meningioma. The 60 patients analysed for tumour characteristics consisted of 32
      females and 28 males (sex ratio 1.1:1) aged 9-77 years (mean 40 years) seen
      between 1977 and 1999 at the University College Hospital, Ibadan, Nigeria. The
      patients for whom sufficient clinical data was available (n=35) presented within
      2-60 months (mean 18 months) of symptom onset with large tumours (mean size 52
      mm), and perifocal oedema (26/35), poor vision, focal neurological deficits,
      seizures and clinical evidence of intracranial hypertension. The most common
      tumour site was the convexity. There was loss of vision in 30/35 (85.7%)
      patients. Loss of vision was significantly related to tumour site and tumour size
      as well as perifocal oedema, (P<0.05). The case-mortality rate was 11.4% at 1
      month and 20% at 6 months post-operation and was significantly correlated with
      intracranial hypertension. Neither age nor sex affected the outcome (P>0.05).

PMID- 16815024
TI  - Diagnostic and therapeutic considerations for sinus pericranii.
AB  - Sinus pericranii is one of the differential diagnoses which should be considered
      when a physician encounters a patient with a subcutaneous soft scalp mass. Sinus
      pericranii is a rare vascular anomaly of the venous drainage between the
      intracranial and extracranial systems via the diploe of the skull. We describe
      here a 16-year-old female with sinus pericranii following minor head trauma four
      years prior. CT and MRI scans revealed heterogeneous enhancement of the lesion
      and three-dimensional CT showed a crater-like depression and multiple honeycomb
      diploic holes in the skull. Angiography was normal, whereas percutaneous
      sinusography revealed a connection between the lesion and the superior sagittal
      sinus. The patient underwent surgery to disconnect her diploic veins from the
      lesion under general anaesthesia, and her postoperative course was uneventful
      after six months follow-up. To avoid profuse bleeding and air emboli and to
      ameliorate cosmetic problems, a specific diagnosis should be made to plan
      appropriate treatment.

PMID- 16815025
TI  - Subgaleal migration of a ventriculoperitoneal shunt.
AB  - Blockage of a ventriculoperitoneal (VP) shunt is very common. Here, we describe
      an unusual case of shunt blockage in an infant. He was shunted for hydrocephalus
      associated with a Dandy-Walker malformation diagnosed at birth. At surgery, the
      entire VP shunt was found to have migrated into the subgaleal space, which
      clinically presented as shunt obstruction. We suggest techniques to avoid this
      rare, but preventable, complication of shunt surgery.

PMID- 16815026
TI  - Bidirectional multisite seizure propagation in the intact isolated hippocampus:
      the multifocality of the seizure "focus".
AB  - Localizing the seizure focus is difficult and frequently, multiple sites are
      found. This reflects our poor understanding of the fundamental mechanisms of
      seizure generation and propagation. We used multisite electrophysiological
      recordings in two seizure models and voltage-sensitive dye imaging, to
      spatiotemporally characterize the initiation and propagation of seizures in an
      intact epileptogenic brain region, the isolated hippocampus. In low-magnesium
      perfusate, seizures always originated in the temporal region, and propagated
      along the septotemporal axis to the septal region. After the seizure spread
      across the hippocampus, the bursts within a seizure became bidirectional, with
      different propagation patterns at different frequencies. When the intact
      hippocampus was separated along the septotemporal axis, independent bidirectional
      activity was observed in the two halves, and region-specific cuts to the tissue
      reveal that the CA3 region is critical for seizure generation and propagation. In
      a second seizure model, using focal tetanic stimulation of the septal and
      temporal CA3 region, seizures always originated at the stimulated site with
      bidirectionality later developing at different frequencies, as noted in the low
      magnesium model, behavior compatible with coupled neuronal network oscillators.
      These data provide novel insights into the dynamic multifocality of seizure onset
      and propagation, revealing that the current concept of a single seizure "focus"
      is complex.

PMID- 16815027
TI  - Activation of apoptotic pathways at muscle fiber synapses is circumscribed and
      reversible in a slow-channel syndrome model.
AB  - In the slow-channel syndrome (SCS) mutant acetylcholine receptors elicit calcium
      overload and myonuclear degeneration at the neuromuscular junction (NMJ), without
      muscle fiber death. Activated caspases are present at SCS motor endplates. We
      hypothesized that SCS represents a limited form of apoptosis. We found condensed
      chromatin and occasional single-strand DNA nicks in degenerating synaptic nuclei.
      Cleaved forms of caspases-3 and -9 were present in mouse SCS muscle homogenates
      and were specifically localized to NMJs. Finally, interruption of cholinergic
      activity by axotomy markedly reduced NMJ caspase activity and improved the
      morphological features of apoptosis at NMJs. These results demonstrate that in
      SCS processes leading to apoptosis may remain compartmentalized and reversible.
      Use of cysteine protease inhibitors may aid in treatment of this and other
      dystrophic muscle and excitotoxic disorders. Identification of extrasynaptic
      factors that prevent the spread of apoptosis in SCS muscle fibers may aid in
      developing treatments for neurological disorders characterized by excitotoxicity
      or apoptosis.

PMID- 16815028
TI  - Diabetes, leukoencephalopathy and rage.
AB  - Longstanding diabetes mellitus damages kidney, retina, peripheral nerve and blood
      vessels, but brain is not usually considered a primary target. We describe direct
      involvement of the brain, particularly white matter, in long-term (9 months)
      experimental diabetes of mice, not previously modeled, correlating magnetic
      resonance (MR) imaging with quantitative histological assessment.
      Leukoencephalopathy and cerebral atrophy, resembling that encountered in diabetic
      humans, developed in diabetic mice and was accompanied by time-related
      development of cognitive changes in behavioural testing. Increased RAGE (receptor
      for advanced glycation end products) expression, a mediator of widespread
      diabetic complications, increased dramatically at sites of white matter damage in
      regions of myelination. RAGE expression was also elevated within neurons,
      astrocytes and microglia in grey matter and within oligodendrocytes in white
      matter. RAGE null diabetic mice had significantly less neurodegenerative changes
      when compared to wild-type diabetic mice. Our findings identify a robust and
      novel model of cerebral, particularly white matter, involvement with diabetes
      associated with abnormal RAGE signaling.

PMID- 16815029
TI  - The insulin-like growth factor-I receptor gene: a downstream target for oncogene
      and tumor suppressor action.
AB  - The insulin-like growth factor-I receptor (IGF-IR) mediates the biological
      actions of both IGF-I and IGF-II. The IGF-IR is expressed in most transformed
      cells, where it displays potent antiapoptotic and cell-survival activities. IGF
      IR levels are tightly regulated by the concerted action of secreted (e.g. peptide
      and steroid hormones, growth factors and cytokines) and cellular (e.g.
      transcription factors, oncogenes and tumor suppressors) factors. The mode of
      action of many tumor suppressors involves transcriptional suppression of the IGF
      IR gene, with a subsequent reduction in cell-surface IGF-IR concentrations and
      IGF-I action. Loss-of-function mutation of tumor suppressors, a common theme in
      human cancer, can lead to aberrant regulation of IGF-IR gene expression.

PMID- 16815031
TI  - Metabolic regulation by the nuclear receptor corepressor RIP140.
AB  - Whereas the importance of activating gene expression in metabolic pathways to
      control energy homeostasis is well established, the contribution of
      transcriptional inhibition is less well defined. In this review we highlight a
      crucial role of RIP140, a transcriptional corepressor for nuclear receptors, in
      the regulation of energy expenditure. Mice devoid of the RIP140 gene are lean,
      exhibit resistance to high-fat-diet-induced obesity, and have increased glucose
      tolerance and insulin sensitivity. Consistent with these observations, RIP140
      suppresses the expression of gene clusters that are involved in lipid and
      carbohydrate metabolism, including fatty acid oxidation, oxidative
      phosphorylation and mitochondrial uncoupling. Therefore, the functional interplay
      between transcriptional activators and the corepressor RIP140 is an essential
      process in metabolic regulation.

PMID- 16815030
TI  - Membrane guanylyl cyclase receptors: an update.
AB  - Recent studies have demonstrated key roles for several membrane guanylyl cyclase
      receptors in the regulation of cell hyperplasia, hypertrophy, migration and
      extracellular matrix production, all of which having an impact on clinically
      relevant diseases, including tissue remodeling after injury. Additionally, cell
      differentiation, and even tumor progression, can be profoundly influenced by one
      or more of these receptors. Some of these receptors also mediate important
      communication between the heart and intestine, and the kidney to regulate blood
      volume and Na+ balance.

PMID- 16815032
TI  - IL-17 production by thymocytes upon CD3 stimulation and costimulation with
      microbial factors.
AB  - IL-17 is a potent proinflammatory cytokine produced by activated memory T cells.
      Recent studies in both human autoimmune diseases and in their animal models have
      indicated that IL-17 rather than IFN-gamma might be the essential T-cell effector
      cytokine in the T-cell mediated autoimmune process. Since the thymus has a
      central role in maintaining T-cell self-tolerance and disturbance of thymic self
      tolerance is implied in various autoimmune diseases, we here investigated the
      capability of murine thymocytes to produce IL-17. Our results indicate that
      thymocytes are a potent source of IL-17 in response to CD3 stimulation and
      various microbial immune stimuli and thereby show different patterns in the
      expression of the proinflammatory cytokines IFN-gamma and IL-17. In addition,
      strong differences between thymocytes and splenocytes were detected. Altered IL
      17 production by thymocytes upon contact with foreign pathogens might be a key
      regulator in the education of adaptive immunity.

PMID- 16815033
TI  - Enzymatic analysis of lipid phosphate phosphatases.
AB  - Lipid phosphate monoesters including phosphatidic acid, lysophosphatidic acid,
      sphingosine 1-phosphate and ceramide 1-phosphate are intermediates in phosho- and
      sphingo-lipid biosynthesis and also play important roles in intra- and extra
      cellular signaling. Dephosphorylation of these lipids terminates their signaling
      actions and, in some cases, generates products with additional biological
      activities or metabolic fates. The key enzymes responsible for dephosphorylation
      of these lipid phosphate substrates are collectively termed lipid phosphate
      phosphatases (LPPs). They are integral membrane enzymes with a core domain of six
      transmembrane spanning alpha-helices linked by extramembrane loops. LPPs are
      oriented in the membrane with their N- and C-termini facing the cytoplasm. LPPs
      exhibit isoform and cell specific localization patterns being variably
      distributed between endomembrane compartments (primarily the endoplasmic
      reticulum and Golgi apparatus) and the plasma membrane. The active site of these
      enzymes is formed from residues within two of the extramembrane loops and faces
      the lumen of endomembrane compartments or, when localized to the plasma membrane,
      towards, the extracellular space. Biochemical, pharmacological, cell biological
      and genetic studies identify roles for LPPs in both intracellular lipid
      metabolism and the regulation of both intra- and extra-cellular signaling
      pathways that control cell growth, survival and migration. This article describes
      procedures for the expression of LPPs in insect and mammalian cells and their
      analysis by SDS-PAGE and Western blotting. The most straightforward way to
      determine LPP activity is to measure release of the substrate phosphate group. We
      described methods for the synthesis and purification of [(32)P]-labeled LPP
      substrates. We describe the use of both radiolabeled and fluorescent lipid
      substrates for the detection, quantitation and analysis of the enzymatic
      activities of the LPPs measured using intact or broken cell preparations as the
      source of enzyme.

PMID- 16815034
TI  - Expression and characterization of recombinant gamma-tryptase.
AB  - Tryptases are trypsin-like serine proteases whose expression is restricted to
      cells of hematopoietic origin, notably mast cells. gamma-Tryptase, a recently
      described member of the family also known as transmembrane tryptase (TMT), is a
      membrane-bound serine protease found in the secretory granules or on the surface
      of degranulated mast cells. The 321 amino acid protein contains an 18 amino acid
      propeptide linked to the catalytic domain (cd), followed by a single-span
      transmembrane domain. gamma-Tryptase is distinguished from other human mast cell
      tryptases by the presence of two unique cysteine residues, Cys(26) and Cys(145),
      that are predicted to form an intra-molecular disulfide bond linking the
      propeptide to the catalytic domain to form the mature, membrane-anchored two
      chain enzyme. We expressed gamma-tryptase as either a soluble, single-chain
      enzyme with a C-terminal His tag (cd gamma-tryptase) or as a soluble
      pseudozymogen activated by enterokinase cleavage to form a two-chain protein with
      an N-terminal His tag (tc gamma-tryptase). Both recombinant proteins were
      expressed at high levels in Pichia pastoris and purified by affinity
      chromatography. The two forms of gamma-tryptase exhibit comparable kinetic
      parameters, indicating the propeptide does not contribute significantly to the
      substrate affinity or activity of the protease. Substrate and inhibitor library
      screening indicate that gamma-tryptase possesses a substrate preference and
      inhibitor profile distinct from that of beta-tryptase. Although the role of gamma
      tryptase in mast cell function is unknown, our results suggest that it is likely
      to be distinct from that of beta-tryptase.

PMID- 16815035
TI  - Purification of prostate-specific membrane antigen using conformational epitope
      specific antibody-affinity chromatography.
AB  - Prostate-specific membrane antigen (PSMA) is a type II membrane protein that has
      attracted significant attention as a target for immunioscintigraphic and
      radioimmunotherapeutic applications for prostate cancer. However, definitive
      studies on its substrate and inhibitor specificity as well as protein-protein
      interactions have been somewhat limited by difficulties in the purification of
      native PSMA. In this study, we optimized the purification of native PSMA from
      LNCaP cells using conformational epitope-specific antibody-affinity
      chromatography. Western blot analysis and an HPLC-based enzymatic activity assay
      were used to compare the yield and activity of PSMA purified by different
      methods. The ratio of purified PSMA in a native and active conformation was
      determined by quantifying the amount of non-native PSMA not retained in a second
      antibody-affinity isolation. The addition of both a neutralization step and the
      inclusion of Zn(2+) to the equilibration buffer in desalting step provides
      considerable enhancement in the yield of active PSMA from LNCaP cells.

PMID- 16815036
TI  - Decomposing intuitive components in a conceptual problem solving task.
AB  - Research into intuitive problem solving has shown that objective closeness of
      participants' hypotheses were closer to the accurate solution than their
      subjective ratings of closeness. After separating conceptually intuitive problem
      solving from the solutions of rational incremental tasks and of sudden insight
      tasks, we replicated this finding by using more precise measures in a conceptual
      problem-solving task. In a second study, we distinguished performance level,
      processing style, implicit knowledge and subjective feeling of closeness to the
      solution within the problem-solving task and examined the relationships of these
      different components with measures of intelligence and personality. Verbal
      intelligence correlated with performance level in problem solving, but not with
      processing style and implicit knowledge. Faith in intuition, openness to
      experience, and conscientiousness correlated with processing style, but not with
      implicit knowledge. These findings suggest that one needs to decompose processing
      style and intuitive components in problem solving to make predictions on effects
      of intelligence and personality measures.

PMID- 16815037
TI  - Multifractal analysis of deep white matter microstructural changes on MRI in
      relation to early-stage atherosclerosis.
AB  - Multifractal analysis based on generalized concepts of fractals has been applied
      to evaluate biological tissues composed of complex structures. This type of
      analysis can provide a precise quantitative description of a broad range of
      heterogeneous phenomena. Previously, we applied multifractal analysis to describe
      heterogeneity in white matter signal fluctuation on T2-weighted MR images as a
      new method of texture analysis and established Deltaalpha as the most suitable
      index for evaluating white matter structural complexity (Takahashi et al. J.
      Neurol. Sci., 2004; 225: 33-37). Considerable evidence suggests that
      pathophysiological processes occurring in deep white matter regions may be partly
      responsible for cognitive deterioration and dementia in elderly subjects. We
      carried out a multifractal analysis in a group of 36 healthy elderly subjects who
      showed no evidence of atherosclerotic risk factors to examine the microstructural
      changes of the deep white matter on T2-weighted MR images. We also performed
      conventional texture analysis, i.e., determined the standard deviation of signal
      intensity divided by mean signal intensity (SD/MSI) for comparison with
      multifractal analysis. Next, we examined the association between the findings of
      these two types of texture analysis and the ultrasonographically measured intima
      media thickness (IMT) of the carotid arteries, a reliable indicator of early
      carotid atherosclerosis. The severity of carotid IMT was positively associated
      with Deltaalpha in the deep white matter region. In addition, this association
      remained significant after excluding 12 subjects with visually detectable deep
      white matter hyperintensities on MR images. However, there was no significant
      association between the severity of carotid IMT and SD/MSI. These results
      indicate the potential usefulness of applying multifractal analysis to
      conventional MR images as a new approach to detect the microstructural changes of
      apparently normal white matter during the early stages of atherosclerosis.

PMID- 16815038
TI  - Effect of spatial smoothing on physiological noise in high-resolution fMRI.
AB  - Physiological noise dominates the SNR of the fMRI time-course at commonly used
      spatial resolutions at field strengths of 3 T and above. Operating in this
      physiological noise dominated regime limits some benefits of high field
      acquisition since increases in image SNR produce only modest increases in time
      course SNR. Although previous studies have shown that the physiological noise
      dominance can be mitigated by using higher spatial resolutions, not all
      functional studies require voxel sizes smaller than the thickness of the human
      cortex. In this study, we examine the effect of acquiring high spatial
      resolution, thermal noise dominated time-courses and spatially smoothing the
      images to lower resolutions, which would otherwise be physiological noise
      dominated. At high field strengths, where physiological noise is most
      problematic, this strategy lowered the overall time-course variance compared to
      direct acquisition at commonly used spatial resolution. At 7 T for example, 5 x 5
      x 3 mm3 resolution images derived from smoothing 1.5 x 1.5 x 3 mm3 data improved
      time-course SNR by a factor of 1.89 compared to a time-series acquired at 5 x 5 x
      3 mm3. Presumably, this effect was derived from the reduced physiological-to
      thermal noise ratio in the high spatial resolution data followed by a smoothing
      operation that improves SNR without adding physiological noise. Our findings
      demonstrate that in contrast to conventional SNR penalties associated with
      spatially smoothing Fourier data, the time-course SNR of smoothed high-resolution
      data can be improved compared to direct acquisition at the desired resolution.

PMID- 16815039
TI  - Magnetoencephalographic evaluation of resting-state functional connectivity in
      Alzheimer's disease.
AB  - Statistical interdependencies between magnetoencephalographic signals recorded
      over different brain regions may reflect the functional connectivity of the
      resting-state networks. We investigated topographic characteristics of disturbed
      resting-state networks in Alzheimer's disease patients in different frequency
      bands. Whole-head 151-channel MEG was recorded in 18 Alzheimer patients (mean age
      72.1 years, SD 5.6; 11 males) and 18 healthy controls (mean age 69.1 years, SD
      6.8; 7 males) during a no-task eyes-closed resting state. Pair-wise
      interdependencies of MEG signals were computed in six frequency bands (delta,
      theta, alpha1, alpha2, beta and gamma) with the synchronization likelihood (a
      nonlinear measure) and coherence and grouped into long distance (intra- and
      interhemispheric) and short distance interactions. In the alpha1 and beta band,
      Alzheimer patients showed a loss of long distance intrahemispheric interactions,
      with a focus on left fronto-temporal/parietal connections. Functional
      connectivity was increased in Alzheimer patients locally in the theta band
      (centro-parietal regions) and the beta and gamma band (occipito-parietal
      regions). In the Alzheimer group, positive correlations were found between
      alpha1, alpha2 and beta band synchronization likelihood and MMSE score. Resting
      state functional connectivity in Alzheimer's disease is characterized by specific
      changes of long and short distance interactions in the theta, alpha1, beta and
      gamma bands. These changes may reflect loss of anatomical connections and/or
      reduced central cholinergic activity and could underlie part of the cognitive
      impairment.

PMID- 16815040
TI  - Using the BOLD MR signal to differentiate the stereoisomers of ketamine in the
      rat.
AB  - RATIONALE: Ketamine is a chiral molecule that is reported to model aspects of
      schizophrenia. OBJECTIVES: To investigate the stereospecificity of the isomers of
      ketamine using pharmacological magnetic resonance imaging (phMRI) in order to
      further understand ketamine's pharmacodynamic actions. METHOD: Responses to 25 mg
      kg-1S(+) isomer, R(-) isomer and racemic ketamine in independent groups of
      Sprague-Dawley rats were investigated using a prepulse inhibition paradigm,
      locomotor observations, MRI and 2-deoxyglucose techniques. RESULTS: Racemic
      ketamine and the S(+) isomer were both capable of disrupting sensorimotor gating
      as measured using prepulse inhibition and produced a longer period of
      hyperlocomotion comparative to the R(-) isomer. In contrast, large alterations in
      the BOLD MR signal were observed with R(-) isomer, whereas S(+) isomer and
      racemate precipitated more localized BOLD signal changes predominantly in
      cortical, hippocampal and hindbrain regions. Glucose utilization rates in
      conscious animals are in agreement with previously published data and verify the
      BOLD responses in the racemic group. However, no significant changes in glucose
      utilization were observed in the anesthetized cohort. CONCLUSIONS: Ketamine and
      its isomers have stereospecific effects on sensorimotor gating and locomotion
      that correlate with the enantiomer's affinity for the NMDA receptor. It would
      appear that anesthesia, as required for preclinical MRI procedures, may interact
      with and potentially attenuate the drug's response. Although analysis of the main
      effect of isomers in comparison to each other or the racemate offers an
      alternative analysis method that should be less susceptible to anesthetic
      interactions, only the R(-) isomer comparative to the racemate offers significant
      differences of interest.

PMID- 16815041
TI  - Subjective feeling of appetite modulates brain activity: an fMRI study.
AB  - Obesity and overweight are important risk factors for the development of diabetes
      mellitus type 2 and associated chronic diseases, and therefore, they have become
      serious global problems in the western and developed countries. But little is
      known about the neuroanatomical correlates of eating behavior and its influences
      on the central nervous processing in humans. We used functional magnetic
      resonance imaging (fMRI) to measure the cortical activation in 12 lean healthy
      humans during visual stimulation with food-related and nonfood pictures after a
      fasting period of at least 5 h. Compared to the nonfood pictures, the food
      stimuli elicited a significantly greater activity in the left orbitofrontal
      cortex and the insular/opercular cortex bilaterally with a stronger focus on the
      left side. Subjective ratings of appetite during the presentation of food-related
      stimuli modulated the activity in the insula bilaterally, the left operculum and
      the right putamen. These results provide further insights in the central nervous
      processing of food relevant stimuli in humans, specifically with respect to the
      subjective experience of appetite.

PMID- 16815042
TI  - A responsive MRI contrast agent to monitor functional cell status.
AB  - It has been shown that insoluble Gd chelates are suitable MRI contrast agents for
      conditional activation by intracellular lipases. The DTPA-based, insoluble,
      inactive contrast agent was internalized into dendritic cells by phagocytosis.
      Cleavage of long aliphatic side chains by intracellular lipase activity leads to
      the contrast agents solubility and hereby its activation depending on the enzyme
      expression. Uptake and activation of the contrast agent was much reduced in Flt3+
      CD11b+ progenitor cells. Detectability limits in the T(1)-weighted MR images were
      estimated in phantoms and in vivo in the rat brain. Marginal toxic effects were
      only observed at very high concentrations of the contrast agent. The chelate can
      easily be modified to be targeted by enzymes expressed during specific change of
      cell status like activation or differentiation. Such a system is suitable for
      functional cellular in vivo MR imaging.

PMID- 16815043
TI  - Genetic divergence and speciation in lowland and montane peruvian poison frogs.
AB  - Amazonia is famous for high biodiversity, and the highlands of the transition
      zone between the Andes and the lowlands of the Amazon basin show particularly
      high species diversity. Hypotheses proposed to explain the high levels of
      diversity in the highlands include repeated parapatric speciation across
      ecological gradients spanning the transition zone, repeated allopatric speciation
      across geographic barriers between the highlands and lowlands, divergence across
      geographic barriers within the transition zone, and simple lineage accumulation
      over long periods of time. In this study, we investigated patterns of divergence
      in frogs of the genus Epipedobates (family Dendrobatidae) using phylogenetic and
      biogeographic analyses of divergence in mitochondrial DNA (1778 aligned positions
      from genes encoding cyt b, 12S and 16S rRNA for 60 Epipedobates and 11 outgroup
      specimens) and coloration (measured for 18 specimens representing nine species in
      Epipedobates). The majority of phenotypic and species diversity in the poison
      frog genus Epipedobates occurs in the transition zone, although two
      morphologically conserved members of the genus are distributed across the
      lowlands of the Amazon basin. Phylogenetic analysis reveals that there is a
      single highland clade derived from an ancestral colonization event in northern
      Peru by a population of lowland ancestry. Epipedobates trivittatus, a widespread
      Amazonian species, is a member of the highland clade that reinvaded the lowlands.
      Comparative analyses of divergence in coloration and mtDNA reveals that
      divergence in coloration among populations and species in the highlands has been
      accelerated relative to the lowlands. This suggests a role for selection in the
      divergence of coloration among populations and species.

PMID- 16815044
TI  - Taxonomic study of the Phyllosoma complex and other triatomine (Insecta:
      Hemiptera: Reduviidae) species of epidemiological importance in the transmission
      of Chagas disease: using ITS-2 and mtCytB sequences.
AB  - The purpose of this work was to clarify the taxonomy and phylogenetic
      relationship of the Phyllosoma complex and other important vectors in Mexico. The
      internal transcribed spacer 2 (ITS-2) of rDNA and the cytochrome B gene of mtDNA
      (mtCytB) were analyzed for the following species of triatomine: Triatoma
      bassolsae, T. longipennis, T. mazzottii, T. mexicana, T. pallidipennis, T.
      picturata, and T. phyllosoma belonging to the Phyllosoma complex, as well as T.
      dimidiata, T. rubida, T. infestans, and Rhodnius prolixus. The results obtained
      with the analysis of the ITS-2 sequences showed that the Phyllosoma complex
      species could not be phylogenetically separated, since T. bassolsae and T.
      pallidipennis, as well as T. phyllosoma and T. mazzottii were indistinguishable.
      In contrast, the mtCytB gene separates each one of these triatomine species. The
      results support the proximity of all seven species currently included in the
      Phyllosoma complex as well as the exclusion of T. dimidiata. For the first time
      T. lecticularia and T. rubida were analyzed and were also shown to be related to
      the Phyllosoma complex.

PMID- 16815045
TI  - Molecular phylogenetics of the spider infraorder Mygalomorphae using nuclear rRNA
      genes (18S and 28S): conflict and agreement with the current system of
      classification.
AB  - Mygalomorph spiders, which include the tarantulas, trapdoor spiders, and their
      kin, represent one of three main spider lineages. Mygalomorphs are currently
      classified into 15 families, comprising roughly 2500 species and 300 genera. The
      few published phylogenies of mygalomorph relationships are based exclusively on
      morphological data and reveal areas of both conflict and congruence, suggesting
      the need for additional phylogenetic research utilizing new character systems. As
      part of a larger combined evidence study of global mygalomorph relationships, we
      have gathered approximately 3.7 kb of rRNA data (18S and 28S) for a sample of 80
      genera, representing all 15 mygalomorph families. Taxon sampling was particularly
      intensive across families that are questionable in composition-Cyrtaucheniidae
      and Nemesiidae. The following primary results are supported by both Bayesian and
      parsimony analyses of combined matrices representing multiple 28S alignments: (1)
      the Atypoidea, a clade that includes the families Atypidae, Antrodiaetidae, and
      Mecicobothriidae, is recovered as a basal lineage sister to all other
      mygalomorphs, (2) diplurids and hexathelids form a paraphyletic grade at the base
      of the non-atypoid clade, but neither family is monophyletic in any of our
      analyses, (3) a clade consisting of all sampled nemesiids, Microstigmata and the
      cyrtaucheniid genera Kiama, Acontius, and Fufius is consistently recovered, (4)
      other sampled cyrtaucheniids are fragmented across three separate clades,
      including a monophyletic North American Euctenizinae and a South African clade,
      (5) of the Domiothelina, only idiopids are consistently recovered as
      monophyletic; ctenizids are polyphyletic and migids are only weakly supported.
      The Domiothelina is not monophyletic. The molecular results we present are
      consistent with more recent hypotheses of mygalomorph relationship; however,
      additional work remains before mygalomorph classification can be formally
      reassessed with confidence-increased taxonomic sampling and the inclusion of
      additional character systems (more genes and morphology) are required.

PMID- 16815046
TI  - An analysis of species boundaries and biogeographic patterns in a cryptic species
      complex: the rotifer--Brachionus plicatilis.
AB  - Since the advent of molecular phylogenetics, there is increasing evidence that
      many small aquatic and marine invertebrates--once believed to be single,
      cosmopolitan species--are in fact cryptic species complexes. Although the
      application of the biological species concept is central to the identification of
      species boundaries in these cryptic complexes, tests of reproductive isolation do
      not frequently accompany phylogenetic studies. Because different species concepts
      generally identify different boundaries in cryptic complexes, studies that apply
      multiple species concepts are needed to gain a more detailed understanding of
      patterns of diversification in these taxa. Here we explore different methods of
      empirically delimiting species boundaries in the salt water rotifer Brachionus
      plicatilis by comparing reproductive data (i.e., the traditional biological
      species concept) to phylogenetic data (the genealogical species concept). Based
      on a high degree of molecular sequence divergence and largely concordant genetic
      patterns in COI and ITS1, the genealogical species hypothesis indicates the
      existence of at least 14 species--the highest estimate for the group thus far. A
      test of the genealogical species concept with biological crosses shows a fairly
      high level of concordance, depending on the degree of reproductive success used
      to draw boundaries. The convergence of species concepts in this group suggests
      that many of the species within the group may be old. Although the diversity of
      the group is higher than previously understood, geographic distributions remain
      broad. Efficient passive dispersal has resulted in global distributions for many
      species with some evidence of isolation by distance over large geographic scales.
      These patterns concur with expectations that micro-meiofauna (0.1-1mm) have
      biogeographies intermediate to microbial organisms and large vertebrates.
      Sympatry of genetically distant strains is common.

PMID- 16815047
TI  - Primate molecular divergence dates.
AB  - With genomic data, alignments can be assembled that greatly increase the number
      of informative sites for analysis of molecular divergence dates. Here, we present
      an estimate of the molecular divergence dates for all of the major primate
      groups. These date estimates are based on a Bayesian analysis of approximately
      59.8 kbp of genomic data from 13 primates and 6 mammalian outgroups, using a
      range of paleontologically supported calibration estimates. Results support a
      Cretaceous last common ancestor of extant primates (approximately 77 mya), an
      Eocene divergence between platyrrhine and catarrhine primates (approximately 43
      mya), an Oligocene origin of apes and Old World monkeys (approximately 31 mya),
      and an early Miocene (approximately 18 mya) divergence of Asian and African great
      apes. These dates are examined in the context of other molecular clock studies.

PMID- 16815048
TI  - Pinniped phylogeny and a new hypothesis for their origin and dispersal.
AB  - The relationships and the zoogeography of the three extant pinniped families,
      Otariidae (sea lions and fur seals), Odobenidae (one extant species, the walrus),
      and Phocidae (true seals), have been contentious. Here, we address these topics
      in a molecular study that includes all extant species of true seals and sea
      lions, four fur seals and the walrus. Contrary to prevailing morphological views
      the analyses conclusively showed monophyletic Pinnipedia with a basal split
      between Otarioidea (Otariidae+Odobenidae) and Phocidae. The northern fur seal was
      the sister to all remaining otariids and neither sea lions nor arctocephaline fur
      seals were recognized as monophyletic entities. The basal Phocidae split between
      Monachinae (monk seals and southern true seals) and Phocinae (northern true
      seals) was strongly supported. The phylogeny of the Phocinae suggests that the
      ancestors of Cystophora (hooded seal) and the Phocini (e.g. harp seal, ringed
      seal) adapted to Arctic conditions and ice-breeding before 12 MYA (million years
      ago) as supported by the white natal coat of these lineages. The origin of the
      endemic Caspian and Baikal seals was dated well before the onset of major
      Pleistocene glaciations. The current findings, together with recent advances in
      pinniped paleontology, allow the proposal of a new hypothesis for pinniped origin
      and early dispersal. The hypothesis posits that pinnipeds originated on the North
      American continent with early otarioid and otariid divergences taking place in
      the northeast Pacific and those of the phocids in coastal areas of southeast N
      America for later dispersal to colder environments in the N Atlantic and the
      Arctic Basin, and in Antarctic waters.

PMID- 16815049
TI  - A molecular assessment of phylogenetic relationships and lineage accumulation
      rates within the family Salamandridae (Amphibia, Caudata).
AB  - We examine phylogenetic relationships among salamanders of the family
      Salamandridae using approximately 2700 bases of new mtDNA sequence data (the
      tRNALeu, ND1, tRNAIle, tRNAGln, tRNAMet, ND2, tRNATrp, tRNAAla, tRNAAsn, tRNACys,
      tRNATyr, and COI genes and the origin for light-strand replication) collected
      from 96 individuals representing 61 of the 66 recognized salamandrid species and
      outgroups. Phylogenetic analyses using maximum parsimony and Bayesian analysis
      are performed on the new data alone and combined with previously reported
      sequences from other parts of the mitochondrial genome. The basal phylogenetic
      split is a polytomy of lineages ancestral to (1) the Italian newt Salamandrina
      terdigitata, (2) a strongly supported clade comprising the "true" salamanders
      (genera Chioglossa, Mertensiella, Lyciasalamandra, and Salamandra), and (3) a
      strongly supported clade comprising all newts except S. terdigitata. Strongly
      supported clades within the true salamanders include monophyly of each genus and
      grouping Chioglossa and Mertensiella as the sister taxon to a clade comprising
      Lyciasalamandra and Salamandra. Among newts, genera Echinotriton, Pleurodeles,
      and Tylototriton form a strongly supported clade whose sister taxon comprises the
      genera Calotriton, Cynops, Euproctus, Neurergus, Notophthalmus, Pachytriton,
      Paramesotriton, Taricha, and Triturus. Our results strongly support monophyly of
      all polytypic newt genera except Paramesotriton and Triturus, which appear
      paraphyletic, and Calotriton, for which only one of the two species is sampled.
      Other well-supported clades within newts include (1) Asian genera Cynops,
      Pachytriton, and Paramesotriton, (2) North American genera Notophthalmus and
      Taricha, (3) the Triturus vulgaris species group, and (4) the Triturus cristatus
      species group; some additional groupings appear strong in Bayesian but not
      parsimony analyses. Rates of lineage accumulation through time are evaluated
      using this nearly comprehensive sampling of salamandrid species-level lineages.
      Rate of lineage accumulation appears constant throughout salamandrid evolutionary
      history with no obvious fluctuations associated with origins of morphological or
      ecological novelties.

PMID- 16815050
TI  - Homocysteine stimulates nuclear factor kappaB activity and interleukin-6
      expression in rat vascular smooth muscle cells.
AB  - It has been reported that chronic inflammation of the vessel wall is a hallmark
      of atherosclerosis. Interleukin-6 (IL-6) is regarded as an important modulator of
      inflammatory events occurring during all stages of atherogenesis. Although many
      factors that induce IL-6 expression have been identified, the effect of
      homocysteine (Hcy) on the expression of IL-6 in atherogenesis and the underlying
      mechanisms are not entirely clear. The objective of the present study was to
      investigate the role of Hcy in IL-6 expression in rat aorta vascular smooth
      muscle cells (VSMCs). After VSMCs were incubated with Hcy for various time
      periods, enzyme-linked immunosorbent assay (ELISA) and semi-quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) were performed to measure the
      expression of IL-6. Electrophoretic mobility shift assay (EMSA) was used to
      examine nuclear factor kappaB (NF-kappaB) activity. Hcy (0.01-0.25 mmol/l)
      significantly increased the expression of IL-6 mRNA and protein in rat VSMCs. The
      increase in IL-6 expression was associated with the activation of NF-kappaB.
      Pyrrolidine dithiocarbamate (PDTC) suppressed Hcy-induced IL-6 release, a finding
      compatible with involvement of reactive oxygen species as second messengers in
      cytokine production mediated by Hcy. The present study has clearly demonstrated
      the ability of Hcy to elicit an inflammatory response in rat VSMCs by stimulation
      of IL-6 production and activation of NF-kappaB. Inflammation activation on vessel
      walls by elevation of Hcy may contribute to the pathogenesis of atherosclerosis.

PMID- 16815051
TI  - Climatic influences on development and survival of free-living stages of equine
      strongyles: implications for worm control strategies and managing anthelmintic
      resistance.
AB  - Development of resistance to anthelmintic drugs by horse strongyles constitutes a
      growing threat to equine health because it is unknown when new drug classes can
      be expected on the market. Consequently, parasite control strategies should
      attempt to maintain drug efficacy for as long as possible. The proportion of a
      parasite population that is not exposed to anthelmintic treatment is described as
      being "in refugia" and although many factors affect the rate at which resistance
      develops, levels of refugia are considered the most important as these parasites
      are not selected by treatment and so provide a pool of sensitive genes in the
      population. Accordingly, treatment should be avoided when pasture refugia are
      small because such treatments will place significant selection pressure for
      resistance on worm populations. Given this new paradigm for parasite control, it
      has become important to identify seasons and circumstances wherein refugia are
      diminished. Free-living stages of equine strongyles are highly dependent on
      climatic influences, and this review summarises studies of strongyle development
      and survival under laboratory and field conditions in Northern (cool) temperate,
      Southern (warm) temperate and subtropical/tropical climates. In Northern
      temperate climates, refugia are smallest during the winter. In contrast, refugia
      are lowest during the summer in warm temperate and subtropical/tropical climates.
      Although adverse seasonal changes clearly have significant effects on the ability
      of free living stages of strongyle nematode parasites to survive and develop,
      available data suggest that climatic influences cannot effectively "clean"
      pastures from one grazing season to the next.

PMID- 16815052
TI  - Study on biological variation of haemostatic parameters in clinically healthy
      dogs.
AB  - Thromboelastography (TEG) may be a valuable supplement to the coagulation assays
      activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin
      time (TT), fibrinogen, antithrombin (AT) and D-Dimer currently used in most
      clinical pathology laboratories. Allowable imprecision and bias reference limits
      for analytical tests can be calculated based on measurements of biological
      variation. No studies to date have examined the effect of biological variation on
      these haemostasis parameters in the same group of dogs. Plasma samples were
      collected after a set protocol once weekly for five consecutive weeks from eight
      healthy dogs (four males and four females) and stored at -80 degrees C until
      analysis. Randomized duplicate coagulation tests and TEG analyses were performed
      on all plasma samples within one run. The data were analyzed for outliers and
      subsequently subjected to nested analysis of variance to obtain the coefficient
      of analytical, intra-individual and inter-individual variation. From these
      objective analytical performance standards for imprecision, critical difference,
      total error and the index of individuality were calculated to assess the utility
      of conventional population-based reference ranges. All the clotting times (aPTT,
      PT and TT), fibrinogen, AT and D-Dimer showed a degree of individuality, which
      may make the use of population-based reference ranges alone an insensitive
      interpretation criterion, whereas a population-based reference interval seems to
      be sensitive for interpreting all TEG parameters. Analytical performance
      standards for imprecision were only met for one of the coagulation assays,
      whereas all TEG parameters except the alpha angle, alpha achieved this analytical
      goal.

PMID- 16815053
TI  - Oncologists' perceptions of cancer pain management in Spain: the real and the
      ideal.
AB  - AIM: Studies in some countries suggest that cancer pain is often not adequately
      controlled, but little is known about the situation in Spain. The objective of
      this study was to identify medical oncologists' perceptions about pain management
      in their patients. METHODS: Two-round Delphi survey of 24 medical oncologists
      from 22 large, geographically diverse hospitals in Spain. Physicians rated each
      of 150 statements on a Likert scale (1=strongly disagree; 5=strongly agree). The
      mean, standard deviation and frequency of replies in three agreement categories
      were calculated for each item. Statements allowing comparison of oncologists'
      perceptions of how pain is managed in routine clinical practice with how it
      should be managed were grouped together and analyzed. RESULTS: The most notable
      discrepancies between the real and the ideal occurred in the failure to provide
      written information or to confirm that patients understand what they are told,
      the lack of comprehensive and systematic evaluation of pain, and the lack of use
      of non-pharmacological treatments (NPTs) for cancer pain. CONCLUSIONS: Medical
      oncologists need to improve their communication skills, providing patients with
      both written and verbal information about their disease and the plan for pain
      management. Pain should be evaluated at each patient visit using validated
      scales, and greater attention should be paid to the possible use of NPTs.

PMID- 16815054
TI  - Generalized deep-tissue hyperalgesia in patients with chronic low-back pain.
AB  - Some chronic painful conditions including e.g. fibromyalgia, whiplash associated
      disorders, endometriosis, and irritable bowel syndrome are associated with
      generalized musculoskeletal hyperalgesia. The aim of the present study was to
      determine whether generalized deep-tissue hyperalgesia could be demonstrated in a
      group of patients with chronic low-back pain with intervertebral disc herniation.
      Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12
      age and sex matched controls were included. Subjects were exposed to quantitative
      nociceptive stimuli to the infraspinatus and anterior tibialis muscles.
      Mechanical pressure (thresholds and supra-threshold) and injection of hypertonic
      saline (pain intensity, duration, distribution) were used. Pain intensity to
      experimental stimuli was assessed on a visual analogue scale (VAS). Patients
      demonstrated significantly higher pain intensity (VAS), duration, and larger
      areas of pain referral following saline injection in both infraspinatus and
      tibialis anterior. The patients rated significantly higher pain intensity to
      supra-threshold mechanical pressure stimulation in both muscles. In patients, the
      pressure pain-threshold was lower in the anterior tibialis muscle compared to
      controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in
      chronic low-back pain patients with radiating pain and MRI confirmed
      intervertebral disc herniation, suggesting that this central sensitization should
      also be addressed in the pain management regimes.

PMID- 16815055
TI  - Spectral reconstruction methods in fast NMR: reduced dimensionality, random
      sampling and maximum entropy.
AB  - The need to reduce data acquisition times of multidimensional NMR experiments has
      fostered considerable interest in novel data acquisition schemes. A recurring
      theme is that of reduced dimensionality experiments, in which time evolutions in
      the indirect dimensions are incremented together, rather than independently.
      Spectral analysis of such data is carried out using methods such as filtered back
      projection, GFT, or parametric signal modeling. By using Maximum Entropy
      reconstruction of reduced-dimensionality data, we show that the artifacts that
      arise in reduced dimensionality experiments are intrinsic to the data sampling,
      and are not, in general, the result of the methods used to compute spectra. Our
      results illustrate that reduced dimensionality is a special case of non-uniform
      sampling in the time domain. We show that MaxEnt reconstruction yields more
      accurate spectra for reduced dimensionality data than back-projection
      reconstruction and that randomly choosing time increments based on an
      exponentially weighted distribution is more efficient, with fewer artifacts, than
      the systematic coupling of time increments used in most reduced dimensionality
      approaches.

PMID- 16815056
TI  - Analysing the pH-dependent properties of proteins using pKa calculations.
AB  - The results of protein pKa calculations are routinely being analysed to
      understand the pH-dependence of protein characteristics such as stability and
      catalysis. Systems of functionally important titratable groups are identified
      from protein from pKa calculations, but the rationalisation of the behaviour of
      such systems is inherently problematic due to a lack of theoretical tools and
      methods. I present a number of novel methods for analysing the results of protein
      pKa calculations which have been embedded in a graphical user interface
      (pKaTool). In the present paper I present novel methods for assessing the
      reliability of protein pKa calculations and for analysing the roles of individual
      residues in determining active site pKa values and the pH-dependence of protein
      stability. The methods presented are freely available to academic researchers at
      http://enzyme.ucd.ie/Science/pKa/pKaTool .

PMID- 16815057
TI  - Montelukast exerts no acute direct effect on NO synthases.
AB  - The cysteinyl leukotrienes (CysLTs) LTC(4), LTD(4) and LTE(4) are potent
      proinflammatory lipid mediators that play a central role in inflammation,
      contraction and remodelling of airways observed in asthmatics. Montelukast, a
      competitive inhibitor of the cysteinyl leukotriene-1 (CysLT(1)) receptor
      attenuates asthmatic airway inflammation, contraction and remodelling. As a
      number of studies have shown that montelukast reduced exhaled nitric oxide (NO)
      levels, a marker of inflammation that correlates with the severity of asthma, we
      investigated whether or not a direct inhibition of NO synthase (NOS) by
      montelukast takes place. In an ex vivo rat lung perfusion and ventilation model
      the NOS-dependent vasodilation effect after lipopolysaccharide (LPS) infusion was
      assessed with and without montelukast. Functional organ bath studies using
      isolated aortic rings from the same species aimed to assess effects of
      montelukast on the inducible and endothelial NOS isoenzymes (i- and eNOS) as well
      as on iNOS expression. Neuronal NOS (nNOS) was assessed by field stimulated
      rabbit corpus cavernosum, and isolated human iNOS enzyme activity was assessed
      for potential inhibition. Montelukast failed to cause vasoconstriction in LPS
      challenged rat lung, or to inhibit i- and eNOS activity as well as iNOS
      expression in aortic rings from the same species. Also the assays for nNOS in
      rabbit corpus cavernosum and on isolated human iNOS enzyme gave no evidence for a
      direct inhibition by montelukast in physiological and supraphysiological
      concentrations up to 10(-4)M. We therefore conclude that montelukast has no acute
      NOS inhibitor action. Its effect on exhaled NO is therefore probably indirectly
      mediated by a modulation of the asthmatic airway inflammation.

PMID- 16815058
TI  - Ontogenic variations in the content and distribution of progesterone receptor
      isoforms in the reproductive tract and brain of chicks.
AB  - Progesterone participates in the regulation of several functions in chicks such
      as ovulation, gonadal differentiation, and sexual and nesting behaviors. Many
      progesterone actions are mediated by specific intracellular receptors (PR) which
      are ligand-induced transactivators. Two PR isoforms that are functionally
      distinct in their ability to activate genes and regulate distinct physiological
      processes have been described in chicks: a full length form PR-B and the N
      terminally truncated one PR-A which lacks the amino-terminal 128 amino acids of
      PR-B. PR isoforms have been detected in several tissues of both the adult and the
      embryo chick such as brain, ovary and oviduct. PR isoforms expression ratio
      varies among progesterone target tissues and under different hormonal and
      environmental conditions such as those presented during avian sexual maturity and
      the seasons of the year. These data let us to conclude that progesterone actions
      in brain, ovary, and oviduct highly depend on PR isoforms expression pattern and
      regulation.

PMID- 16815059
TI  - Testosterone metabolism in Neomysis integer following exposure to benzo(a)pyrene.
AB  - Cytochromes P450 (CYPs) are important enzymes involved in the regulation of
      hormone synthesis and in the detoxification and/or activation of xenobiotics.
      CYPs are found in virtually all organisms, from archae, and eubacteria to
      eukaryota. A number of endocrine disruptors are suspected of exerting their
      effects through disruption of normal CYP function. Consequently, alterations in
      steroid hormone metabolism through changes in CYP could provide an important tool
      to evaluate potential effects of endocrine disruptors. The aim of this study was
      to investigate the potential effects of the known CYP modulator, benzo(a)pyrene
      (BaP), on the testosterone metabolism in the invertebrate Neomysis integer
      (Crustacea; Mysidacea). N. integer were exposed for 96 h to 0.43, 2.39, 28.83,
      339.00 and 1,682.86 microg BaP L(-1) and a solvent control, and subsequently
      their ability to metabolize testosterone was assessed. Identification and
      quantification of the produced phase I and phase II testosterone metabolites was
      performed using liquid chromatography coupled with multiple mass spectrometry (LC
      MS2). Significant changes were observed in the overall ability of N. integer to
      metabolize testosterone when exposed to 2.39, 28.83, 339.00 and 1,682.86 microg
      BaP L(-1) as compared to the control animals.

PMID- 16815060
TI  - Low-molecular-weight chromium-binding substance from chicken liver and American
      alligator liver.
AB  - Low-molecular-weight chromium-binding substance (LMWCr), also known as
      chromodulin, is a chromium-binding oligopeptide proposed to have a function in
      chromium transport and insulin signaling in mammals. In this work, LMWCr has been
      isolated and purified for the first time from non-mammalian sources: chicken and
      American alligator. Milligram quantities of the oligopeptide can be obtained from
      kilogram quantities of liver. The LMWCr's from both sources are asparatate- and
      glutamate-rich oligopeptides which possess multinuclear chromium assemblies. The
      composition and physical and spectroscopic properties of the avian and reptilian
      LMWCr's are extremely similar to those of their mammalian analogues, suggesting
      the multinuclear sites of the biomolecule from all three classes of animal
      possess very similar structures. The chicken and alligator oligopeptides may
      possess intrinsic phosphotyrosine phosphatase activity.

PMID- 16815061
TI  - MMP-2 in the left rat ventricle is increased by growth hormone.
AB  - In cardiac hypertrophy induced by GH, the turn-over of collagen seems to be
      increased. Matrix metalloproteinases (MMP) are enzymes suggested to contribute to
      the remodelling of the extracellular matrix in the myocardium. The aim of the
      present experiment was to investigate how GH influenced MMP concentration,
      collagen concentration, and structure of the connective tissue of the LV in young
      rats in relation to time. Three-month-old female rats were injected with GH
      (5mg/kg/day) or vehicle for 5, 10, 20, 40, or 80 days. MMPs and structural
      changes of the connective tissue were analysed using zymography and stereology,
      respectively. Wet weight of the LV was increased time-dependently by GH (r =
      0.89, P < 0.001). Furthermore, GH increased the MMP-2 concentration (P < 0.01,
      two-way ANOVA), whereas no collagenases (MMP-1, MMP-8, or MMP-13) could be
      demonstrated. The increase in MMP-2 was accompanied by a time-dependent decrease
      in the collagen concentration (r = -0.46, P < 0.05), whereas the total collagen
      content (r = 0.85, P < 0.01) and total number of non-myocyte nuclei (GH: r =
      0.89, P < 0.001) were time-dependently increased. These results indicate that MMP
      2 may be involved in the remodelling process of the extracellular matrix in GH
      induced cardiac hypertrophy.

PMID- 16815062
TI  - Coenzyme Q10 production in recombinant Escherichia coli strains engineered with a
      heterologous decaprenyl diphosphate synthase gene and foreign mevalonate pathway.
AB  - In the present work, Escherichia coli DH5alpha was metabolically engineered for
      CoQ(10) production by the introduction of decaprenyl diphosphate synthase gene
      (ddsA) from Agrobacterium tumefaciens. Grown in 2YTG medium (1.6% tryptone, 1%
      yeast extract, 0.5% NaCl, and 0.5% glycerol) with an initial pH of 7, the
      recombinant E. coli was capable of CoQ(10) production up to 470 microg/gDCW (dry
      cell weight). This value could be further elevated to 900 microg/gDCW simply by
      increasing the initial culture pH from 7 to 9. Supplementation of 4-hydroxy
      benzoate did not improve the productivity any further. However, engineering of a
      lower mevalonate semi-pathway so as to increase the isopentenyl diphosphate (IPP)
      supply of the recombinant strain using exogenous mevalonate efficiently increased
      the CoQ(10) production. Lower mevalonate semi-pathways of Staphylococcus aureus,
      Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, and
      Saccharomyces cerevisiae were tested. Among these, the pathway of Streptococcus
      pneumoniae proved to be superior, yielding CoQ(10) production of 2,700+/-115
      microg/gDCW when supplemented with exogenous mevalonate of 3 mM. In order to
      construct a complete mevalonate pathway, the upper semi-pathway of the same
      bacterium, Streptococcus pneumoniae, was recruited. In a recombinant E. coli
      DH5alpha harboring three plasmids encoding for upper and lower mevalonate semi
      pathways as well as DdsA enzyme, the heterologous mevalonate pathway could
      convert endogenous acetyl-CoA to IPP, resulting in CoQ(10) production of up to
      2,428+/-75 microg/gDCW, without mevalonate supplementation. In contrast, a whole
      mevalonate pathway constructed in a single operon was found to be less efficient.
      However, it provided CoQ(10) production of up to 1,706+/-86 microg/gDCW, which
      was roughly 1.9 times higher than that obtained by ddsA alone.

PMID- 16815063
TI  - Clinical, cytological and histopathological evaluation of mammary masses in cats
      from Rio de Janeiro, Brazil.
AB  - The vast majority of mammary tumors in cats are malignant with high metastatic
      and mortality rates. This study evaluated clinical, cytological and
      histopathological aspects of 20 cases of cat mammary masses deriving from the
      city of Rio de Janeiro. Data on history, macroscopic description, evidence of
      regional lymph node and distant metastases, clinical examination and treatment
      were collected. The cats were treated with unilateral mastectomy, unilateral
      mastectomy plus chemotherapy or chemotherapy alone. Tissues were submitted for
      cytological and histological evaluation. Histopathological analysis described one
      case of mammary hyperplasia and 19 cases of adenocarcinoma. Inadequate surgical
      margins were obtained in two cats while six showed evidence of microscopic
      invasion in other mammary glands. Multiple mammary involvement and greater tumor
      size (diameter over 7.05 cm) were correlated with increased chance of local
      metastases. Ulceration of tumors and metastases were common. These facts support
      the highly malignant nature of this neoplasia and emphasize the risks associated
      with delay in diagnosis and treatment of feline patients. In conclusion, mammary
      palpation should be performed routinely in the clinical practice.

PMID- 16815064
TI  - Antimicrobial resistance in clinical isolates of Staphylococcus aureus from
      hospital and community sources in southern Jamaica.
AB  - OBJECTIVES: In this study, we assessed the antimicrobial susceptibility patterns
      and prevalence of methicillin resistance among Staphylococcus aureus isolates
      from hospital and community sources in southern Jamaica. METHODS: Eighty isolates
      of S. aureus obtained from hospital and community-based patients with
      staphylococcal infections were collected, and antimicrobial susceptibilities were
      determined by disk diffusion. RESULTS: While all specimens yielded isolates,
      multidrug-resistant isolates were obtained only from urine, high vaginal swab,
      abscess aspirate, and catheter tip samples. The overall prevalence of methicillin
      resistant S. aureus (MRSA) was 23%. The proportions of MRSA isolated from
      hospital sources (18/39) and community sources were 46% and 0%, respectively
      (p<0.05). The pattern of antibiotic susceptibility of S. aureus differed
      significantly between MRSA and methicillin-susceptible (MSSA) isolates. For MRSA
      isolates, multiple-drug resistance was common and only few antibiotics were
      active against these isolates. However, no MRSA was resistant to vancomycin.
      Except for penicillin and to some extent co-trimoxazole (trimethoprim
      sulfamethoxazole), most MSSA isolates were susceptible to nearly all
      antimicrobial agents used in this study. CONCLUSIONS: This is the first report of
      MRSA from this region of Jamaica. Because methicillin resistance is associated
      with multiple-drug resistance in S. aureus, it is imperative that surveillance
      initiatives be focused on both the hospital and community in order to monitor and
      limit the spread of this organism.

PMID- 16815065
TI  - Bacteremia in adult patients with acquired immunodeficiency syndrome in the
      northeast of Thailand.
AB  - BACKGROUND: Bacteremia is a frequent complication found in HIV-infected patients
      and is usually associated with a poor prognosis. This study was undertaken to
      describe the bacterial pathogens causing bacteremia in adult Thai HIV-infected
      patients, and hence to give guidance in the choice of empirical antimicrobials.
      METHODS: Blood culture results at Srinagarind Hospital, Khon Kaen during the
      period January 1996 to December 2001 were retrospectively reviewed. RESULTS: In
      HIV-infected and HIV-uninfected patients, 172 and 4082 episodes of bacteremia
      occurred, respectively. In HIV-infected patients, community-acquired and
      nosocomial bacteremia were found in 78.5% and 21.5%, respectively and most were
      monomicrobial. Gram-negative bacteria were the main pathogens isolated in both
      groups of bacteremia. Escherichia coli and methicillin-resistant Staphylococcus
      aureus were more common pathogens causing nosocomial bacteremia in HIV-infected
      patients, whereas Acinetobacter spp were more common in HIV-uninfected patients.
      Salmonella spp, especially Salmonella groups D and B, were the most common
      (62.2%) pathogen in community-acquired bacteremia in HIV-infected patients
      whereas Escherichia coli was the most common in HIV-uninfected patients. Only a
      few episodes of community-acquired bacteremia in HIV-infected patients had
      identified sources. Co-trimoxazole resistance was common in community-acquired
      bacteremia caused by Gram-negative bacilli in HIV-infected patients, with
      Salmonella group B being more resistant to co-trimoxazole than Salmonella group D
      (statistically significant, p<0.001). However, resistance rates to ceftriaxone
      and ofloxacin were low. CONCLUSIONS: Bacteremia in adult HIV-infected patients
      was usually caused by Gram-negative bacilli in both community-acquired and
      nosocomial settings. Salmonella spp was the most common organism identified,
      especially Salmonella group B and D. Ceftriaxone or fluoroquinolones such as
      ofloxacin or ciprofloxacin should be used as the initial empiric therapy for HIV
      infected patients with suspected bacteremia.

PMID- 16815066
TI  - Surface protease of Treponema denticola hydrolyzes C3 and influences function of
      polymorphonuclear leukocytes.
AB  - Treponema denticola is a dominant microorganism in human periodontal lesions. One
      of the major virulence factors of this microorganism is its chymotrypsin-like
      surface protease, dentilisin. The purpose of this study was to evaluate the
      effect of dentilisin on human polymorphonuclear leukocytes (PMNs). We used
      chemiluminescence to assess production of O(-)(2) by PMNs against T. denticola
      ATCC 35405 and dentilisin-deficient mutant K1. T. denticola ATCC 35405 induced
      production of O(-)(2), whereas dentilisin-deficient K1 did not. We found that
      chymostatin, a protease inhibitor, strongly reduced the ability of T. denticola
      ATCC 35405 to induce production of, O(-)(2), whereas K1 was relatively
      unaffected. We also used Immunoblot and ELISA to evaluate the activation of
      complement by this microorganism in relation to PMNs. T. denticola ATCC 35405
      hydrolyzed the alpha-chain of C3, producing iC3b. Furthermore, strain ATCC 35405
      induced a larger release of MMP-9 from PMNs than strain K1. Dentilisin activated
      PMNs via complement pathways and may play a role in establishing periodontal
      lesions.

PMID- 16815067
TI  - Determinant role for Toll-like receptor signalling in acute mycobacterial
      infection in the respiratory tract.
AB  - Toll-like receptors (TLRs) are a vital component of the innate branch of the
      immune system in its battle against mycobacterial infections. Extensive in vitro
      studies have demonstrated a role for both TLR2 and TLR4 in recognition of
      mycobacterial components, whereas the in vivo situation appears less clear, with
      results depending on the infection model. In the present work, the importance of
      TLR signalling in the course of mycobacterial infection was investigated in a
      human-like infection model using TLR-knockout mice. TLR2(-/-) and TLR4(-/-) mice
      infected with Mycobacterium tuberculosis by aerosol, or for the first time,
      intranasally with Mycobacterium bovis bacillus Calmette-Guerin (BCG), displayed
      increased susceptibility at an early stage of infection in the respiratory tract,
      while at a later stage of infection, the TLR deficiency appeared to be overcome.
      The higher susceptibility was correlated to impaired pro-inflammatory responses
      to BCG components, and reduced induction of anti-bacterial activity by infected
      macrophages from TLR2(-/-) mice, and to a lesser extent from TLR4(-/-) mice.
      These findings demonstrate a role for TLR signalling in protection against
      mycobacterial infection specifically in the respiratory tract at the acute phase,
      whereas the TLR deficiency can be compensated at a later stage of infection.

PMID- 16815068
TI  - Establishment of a new cell line inducibly expressing HIV-1 protease for
      performing safe and highly sensitive screening of HIV protease inhibitors.
AB  - The human immunodeficiency virus type 1 (HIV-1) protease (PR) plays an essential
      role in processing viral polyproteins into mature proteins. As a result, it is a
      major target for the development of drugs against AIDS. However, due to the rapid
      emergence of drug-resistant HIV, the development of novel HIV PR inhibitors is
      urgently needed. We recently established a new cell line E-PR293 which can be
      used as a safe, convenient and highly efficient assay system to screen HIV-1 PR
      inhibitors. In the cells, the HIV-1 PR is expressed in a chimeric protein with
      the green fluorescence protein (GFP). This assay measures the PR activity as a
      function of either the fluorescence of GFP or the cytotoxic activity of HIV-1 PR
      which is expressed in the cell. E-PR293 cells were maintained in the presence of
      doxycycline, which suppresses the expression of HIV-1 PR. The removal of
      doxycycline induces the expression of HIV-1 PR, which is used to screen HIV-1 PR
      inhibitors. In E-PR293 cells, the 50% inhibitory concentration of the cytotoxic
      effects by nelfinavir and saquinavir were as low as nanomolar levels, almost
      equal to those found in the HIV-infection assay.

PMID- 16815069
TI  - Toll-like receptor agonists stimulate differential functional activation and
      cytokine and chemokine gene expression in heterophils isolated from chickens with
      differential innate responses.
AB  - Heterophils isolated from distinct broilers (lines A and B) differ in function
      and cytokine gene expression profiles. Nothing is known about Toll-like receptor
      (TLR) expression nor functional activation and cytokine/chemokine gene expression
      of line A and B heterophils when stimulated with TLR agonists. We found that line
      A and B heterophils express the same range of TLRs. All the bacterial TLR
      agonists, peptidoglycan, the synthetic lipoprotein Pam3CSK4, ultra-pure
      lipopolysaccharide, and flagellin all induced significantly greater functional
      activation of heterophils from line A compared to B. Only stimulation with the
      guanosine analog, loxoribine, (LOX) induced a significantly greater functional
      response in B over A. Additionally, all heterophils from line A stimulated with
      the bacterial TLR agonists had dramatic upregulation of pro-inflammatory cytokine
      and chemokine mRNA expression, whereas heterophils from line B had little or no
      upregulation of these genes. However, stimulation of all heterophils from line B
      with the bacterial TLR agonists and LOX induced a significant upregulation of IFN
      alpha, with little transcription of this cytokine gene in line A heterophils.
      These findings suggest that the difference in heterophil functional efficiency
      between these parent lines is due to recognition of pathogens and activation of
      signaling pathways that induce innate cytokine and chemokine responses.

PMID- 16815070
TI  - Aggravated infection in mice co-administered with Mycobacterium tuberculosis and
      the 27-kDa lipoprotein.
AB  - We have previously reported that mice immunized with the mycobacterial 27-kDa
      lipoprotein were more susceptible to Mycobacterium tuberculosis (Mtb) challenge.
      We also showed that 27-kDa lipoprotein abrogated the protection afforded by the
      BCG vaccine when administrated together, suggesting that the 27-kDa lipoprotein
      may modulate the course of experimental mycobacterial infection. In this study,
      we address the role of the 27-kDa lipoprotein in modulating the immune response
      to mycobacteria. Our results show that co-administration of BALB/c mice with Mtb
      and the 27-kDa lipoprotein (Mtb+27kDa), but not its non-acylated form, increases
      the susceptibility of mice to Mtb infection. Significantly lower DTH reaction and
      splenocyte proliferation to PPD stimulation were also observed in Mtb+27kDa
      infected mice compared to Mtb-infected mice. Furthermore, during infection,
      splenocytes and purified T cells lost their ability to proliferate in response to
      concanavalin A stimulation more rapidly in the Mtb+27kDa-infected mice, which was
      accompanied by high IFN-gamma and NO production, but low TNF-alpha secretion
      levels. Addition of L-NMMA, anti-IFN-gamma and anti-TNF-alpha antibodies restored
      in vitro proliferative responses of T cells from Mtb+27kDa-infected mice. Short
      term L-NMMA treatment of Mtb+27kDa-infected mice prevented the 27-kDa-mediated
      immunosuppression and increase in susceptibility to Mtb. Altogether, these data
      suggest that the 27-kDa lipoprotein plays a role in Mtb infection by inducing
      increased suppression of the immune response due to elevated NO production.

PMID- 16815071
TI  - Neurocysticercal antigens stimulate chemokine secretion from human monocytes via
      an NF-kappaB-dependent pathway.
AB  - Neurocysticercosis, infection with larval Taenia solium, is a common, serious
      neuroparasitic infection. Larval degeneration results in inflammatory cell influx
      and granuloma formation which leads to clinical symptomatology. The role of
      chemokines in such cell influx is unknown. We demonstrate that monocyte
      stimulation by T. solium larval antigen (TsAg) results in a differential profile
      of CXCL8/IL-8 (146.5+/-8.5ng/ml after 24h), CCL2/MCP-1 (267+/-4 ng/ml after 48 h)
      and CCL3/MIP-1alpha (1.72+/-0.43 ng/ml after 8 h) secretion. There was coordinate
      mRNA accumulation reaching maximum at 1h for CCL3 and 2 h for CXCL8 and CCL2.
      TsAg induced maximal nuclear binding of p65, p50 and c-rel subunits of the
      transcriptional regulator NF-kappaB by 2 h. IkappaBalpha but not IkappaBbeta was
      degraded within 10 min before resynthesis by 2 h. Pre-treatment with the broad
      spectrum NF-kappaB inhibitor pyrrolidine dithiocarbamate caused complete
      abrogation of TsAg-induced CCL2 secretion (p=0.005) and 91% reduction of CXCL8
      secretion (p=0.0003). TsAg was unable to induce CXCL8 promoter activity in Toll
      like receptor (TLR)-2 or TLR-4/MD-2 transfected HeLa cells in the absence of
      lectins or other adaptor molecules. In summary, our data demonstrate that TsAg
      induces chemokine secretion via specific pathways dependent on NF-kappaB but not
      TLR-4/TLR-2, and indicate a potential mechanism whereby larval degeneration
      results in brain inflammation.

PMID- 16815072
TI  - Herpes simplex virus US3 protein kinase regulates virus-induced apoptosis in
      olfactory and vomeronasal chemosensory neurons in vivo.
AB  - A role for the US3 protein kinase of herpes simplex virus (HSV) in regulating
      virus-induced neuronal apoptosis was investigated in an experimental mouse
      system, in which wild-type HSV invades the central nervous system (CNS) via the
      olfactory and vomeronasal systems upon intranasal infection. Wild-type HSV-2
      strain 186 infected a fraction of olfactory and vomeronasal chemosensory neurons
      without inducing apoptosis and was transmitted to the CNS, precipitating lethal
      encephalitis. In sharp contrast, an US3-disrupted mutant, L1BR1, induced neuronal
      apoptosis in these peripheral conduits upon infection, blocking viral
      transmission to the CNS and causing no signs of disease. An US3-repaired mutant,
      L1B(-)11, behaved similarly to the wild-type virus. Only 5 p.f.u. of L1BR1 was
      sufficient to compromise mice when the mutant virus was introduced directly into
      the olfactory bulb, a viral entry site of the CNS. These results suggest that the
      US3 protein kinase of HSV regulates virus-induced neuronal apoptosis in
      peripheral conduits and determines the neuroinvasive phenotype of HSV.
      Furthermore, virus-induced neuronal apoptosis of peripheral nervous system cells
      may be a protective host response that blocks viral transmission to the CNS.

PMID- 16815073
TI  - Perceived environmental determinants of physical activity and fruit and vegetable
      consumption among high and low socioeconomic groups in the Netherlands.
AB  - A focus group study was conducted to explore how perceptions of environmental
      influences on health behaviours pattern across socioeconomic groups in the
      Netherlands. Participants perceived their spouse's and friend's health behaviour
      and support as highly important. People from lower socioeconomic backgrounds
      reported poor neighbourhood aesthetics, safety concerns and poor access to
      facilities as barriers for being physically active, while easy accessibility to
      sports facilities was mentioned by high socioeconomic participants. The
      availability of fruits and vegetables at home was perceived as good by all
      particpants. Overall, lower socioeconomic groups expressed more price concerns.
      Possible pathways between socioeconomic status, environmental factors and health
      behaviours are represented in a framework, and they should be investigated
      further in longitudinal research.

PMID- 16815074
TI  - Spatial patterns of malaria in the Amazon: implications for surveillance and
      targeted interventions.
AB  - A measure of local spatial association, G(i)*(d), is applied to test for the
      presence of malaria clusters in a colonization area in the Brazilian Amazon.
      Clusters of high and low malaria rates at different moments in time are
      identified. They suggest unambiguous spatial patterns of transmission, most
      likely linked to the social and natural habitat. Results imply that a
      comprehensive identification of the determinants of malaria transmission requires
      a spatial framework of analysis, and that control strategies must be spatially
      targeted and guided by a surveillance system that constantly learns the
      specificities of local transmission and adapts interventions to them.

PMID- 16815075
TI  - The gamma subunit of Na+, K+-ATPase: role on ATPase activity and regulatory
      phosphorylation by PKA.
AB  - In kidney, Na+, K+-ATPase is an oligomer (alphabeta gamma) with equimolar amounts
      of essential alpha and beta subunits and one small hydrophobic FXYD protein
      (gamma subunit). This report describes gamma subunit as an activator of pig
      kidney outer medulla Na+, K+-ATPase in aqueous medium. The effects of gamma
      subunit on Na+, K+-ATPase were dose-dependent and preincubation-dependent.
      Changes in alphabeta/gamma stoichiometry did not alter Km1 for ATP, and slightly
      increased Km2, but Vmax was increased at both catalytic and regulatory sites.
      Hydroxylamine treatment of enzyme phosphorylated by ATP (E-P), in the presence of
      additional gamma subunit, revealed that 52% of the E-P accumulation was not via
      acyl-phosphate formation. The gamma subunit was phosphorylated by endogenous
      kinases and by commercial catalytic subunit of protein kinase A (PKA).
      Additionally, we demonstrated that PKA phosphorylation of gamma subunit increased
      its capacity to stimulate ATP hydrolysis. These results suggest that gamma
      subunit can act as an intrinsic Na+, K+-ATPase regulator in kidney.

PMID- 16815076
TI  - IL-15/IL-15 receptor biology: a guided tour through an expanding universe.
AB  - The cytokine interleukin-15 (IL-15) has a key role in promoting survival,
      proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its
      functional similarities to IL-2, IL-15 affects a wider range of target cell
      populations and utilizes different mechanisms of signaling. Here, we review
      recent advances in the IL-15-mediated signaling, and in the functional properties
      on cells besides T lymphocytes and NK cells. These are discussed in the context
      of their potential clinical and therapeutic relevance.

PMID- 16815077
TI  - Neuroendocrine neoplasms of the larynx: advances in identification,
      understanding, and management.
AB  - While 85-90% of laryngeal malignancies prove to be squamous carcinomas, the
      second most common tumour type found in the laryngeal region will prove to be a
      member of the family of neuroendocrine tumours. Laryngeal carcinoid tumours have
      a capacity for metastasis, and so are more aggressive tumours than their light
      microscopic features might imply--5-year survival rates are in the vicinity of
      50%. Laryngeal atypical carcinoid tumours are lesions with a well-recognized
      capacity for local recurrence as well as metastasis, with a 5-year survival of
      just under 50%. Laryngeal small cell neuroendocrine carcinomas are particularly
      aggressive tumours, with a 5-year survival of no more than 5-10%. Laryngeal
      paragangliomas are lesions without any real capacity for metastasizing. Surgical
      excision is the mainstay of treatment of carcinoid tumours, atypical carcinoid
      tumours, and paragangliomas. Small cell neuroendocrine carcinomas are chiefly
      treated by way of radiation and chemotherapy; the role of adjuvant therapy in the
      treatment of atypical carcinoid tumours remains to be established.

PMID- 16815078
TI  - Candida albicans biofilm development, modeling a host-pathogen interaction.
AB  - Medical device-associated infections involve the attachment of cells to a
      surface, production of an extracellular matrix and development of a mature
      biofilm. Many Candida albicans disease states involve biofilm growth. These
      infections have great impact on public health because organisms in biofilms
      exhibit dramatically reduced susceptibility to antifungal therapy. Progression to
      a mature biofilm is dependent on cell adhesion, extracellular matrix production
      and the yeast-to-hyphae transition. Numerous in vitro biofilm model systems have
      been successfully used to examine biofilm architecture, development, cell
      phenotypes and drug resistance. Although these studies have included a number of
      experimental variables to mimic infections in patients, it is difficult to
      accurately account for the multitude of host and infection-site variables that
      are probably important in humans. Recent studies have begun to explore C.
      albicans biofilms using animal biofilm infection models in order to more
      completely reflect the complexity of this host-fungal interaction.

PMID- 16815079
TI  - SFTG international collaborative study on in vitro micronucleus test I. General
      conditions and overall conclusions of the study.
AB  - This study, coordinated by the SFTG (French branch of European Environmental
      Mutagen Society), included 38 participants from Europe, Japan and America.
      Clastogens (bleomycin, urethane), including base and nucleoside analogs (5
      fluorouracil and cytosine arabinoside), aneugens and/or polyploidy inducers
      (colchicine, diethylstilboestrol, griseofulvin and thiabendazole), as well as non
      genotoxic compounds (mannitol and clofibrate), were tested. Four cell types were
      used, i.e. human lymphocytes in the presence of cytochalasin B and CHO, CHL and
      L5178Y cell lines, in the presence or absence of cytochalasin B, with various
      treatment-recovery schedules. Mitomycin C was used as a positive control for all
      cell types. Mannitol and clofibrate were consistently negative in all cell types
      and with all treatment-recovery conditions. Urethane, known to induce
      questionable clastogenicity, was not found as positive. Bleomycin and mitomycin C
      were found positive in all treatment-recovery conditions. The base and nucleoside
      analogs were less easy to detect, especially 5-fluorouracil due to the
      interference with cytotoxicity, while cytosine arabinoside was detected in all
      cell types depending on the treatment-recovery schedule. Aneugens (colchicine,
      diethylstilboestrol and griseofulvin) were all detected in all cell types. In
      this study, the optimal detection was ensured when a short treatment followed by
      a long recovery was associated with a long continuous treatment without recovery.
      There was no impact of the presence or absence of cytochalasin B on the detection
      of micronucleated cells on cell lines. Scoring micronucleated cells in both
      mononucleated and binucleated cells when using cytochalasin B was confirmed to be
      useful for the detection and the identification of aneugens. In conclusion, these
      results, together with previously published validation studies, provide a useful
      contribution to the optimisation of a study protocol for the detection of both
      clastogens and aneugens in the in vitro micronucleus test.

PMID- 16815080
TI  - Hydrothermal preparation and luminescence of LaF3:Eu3+ nanoparticles.
AB  - LaF3:Eu3+ nanoparticles were prepared by a simple hydrothermal process at low
      temperature and characterized by X-ray diffraction (XRD), transmission electron
      microscopy (TEM) and fluorescence spectrum. Well-dispersed nanoparticles with an
      average size of 30 nm and a hexagonal shape were obtained. The influences of
      reaction temperature and time on the preparation and luminescence of LaF3:Eu3+
      nanoparticles were investigated. Luminescent quenching occurred at a much higher
      concentration ( approximately 25mol%) and stronger luminescent intensity than in
      bulk LaF3:Eu3+. Fluorescence intensity of the LaF3:Eu3+ nanoparticles varied
      remarkably with calcination temperatures. It was found that samples without any
      further calcinations can emit quite strong fluorescence.

PMID- 16815081
TI  - Spectroscopic studies of molecular interactions involving 2,6-diethylaniline and
      N-ethylaniline donors and iodine as an electron acceptor in different solvents.
AB  - The charge-transfer complexes of 2,6-diethylaniline (DEA) and N-ethylaniline
      (NEA) with iodine, as a typical sigma-acceptor were studied
      spectrophotometrically in chloroform, dichloromethane and carbontetrachloride
      solutions. Spectral data, formation constants and effect of solvent have been
      determined. Spectral characteristics and formation constants are discussed in the
      terms of donor molecular structure and solvent polarity. The stoichiometry of the
      complexes was established to be 1:1. For this purpose, optical data were
      subjected to the form of the Rose-Drago equation for 1:1 equilibria. The
      formation constant (KAD) and molar absorptivities (epsilonlambda) of complexes
      were determined by least square method. Electronic absorption spectra of the
      anilines were measured in different solvents. Spectral data were reported and
      band maxima were assigned to the appropriate molecular orbital transitions.
      Quantum chemical calculations were performed with the aid of the Gaussian 98 set
      of programs. The structure were fully optimized at MP2 level using 6-31+G** basis
      set. The computations show that DEA is not planner with the amino group having a
      somewhat sp3 hybridization-like character.

PMID- 16815082
TI  - Single site electronic spectroscopy of palladium chlorin in n-octane matrixes at
      7K.
AB  - The high resolution, single site emission and absorption spectra of palladium
      chlorin (PdC) in n-octane matrixes at 7K are reported. The emission and Q and
      Soret band absorption regions were investigated. The vibrational frequencies of
      the ground and the lowest energy pipi* excited states were determined from
      luminescence and excitation spectra, respectively. The emission from PdC was
      entirely phosphorescence. The emission and Qy region spectra of the complex are
      similar, having intense, narrow origin bands followed by relatively weak but
      orderly vibrational structure. The Qx region of this metal chlorin does not have
      a clear origin and exhibits complex vibrational structure which increases in
      intensity going to higher energy. In the Soret region of PdC there is only a
      single intense, broad band.

PMID- 16815083
TI  - Reactivity of aromatic amines with triplet 1,8-dihydroxyanthraquinone: a laser
      flash photolysis study.
AB  - The property of the lowest excited triplet states of 1,8-dihydroxyanthraquinone
      (DHAQ) was investigated by using time-resolved laser flash photolysis at 355nm in
      organic solvents, i.e. acetonitrile and cyclohexane. The transient absorption
      spectra of the excited triplet DHAQ were obtained in acetonitrile, which have an
      absorption maximum at 480nm and two broad absorption bands around 350 and 650nm.
      3DHAQ(*) is efficiently quenched by triphenylamine (TPA) via photoinduced
      electron transfer pathway, which was testified by the finding of TPA radical
      cation. In addition, aniline derivatives such as N,N-dimethylaniline (DMA),
      3,5,N,N-tetramethylaniline (TMA), 4-dimethylaminobenzoic acid (DMABA) and
      dimethyl-p-toluidine (DMT) could also quench 3DHAQ(*) rapidly. Evidence for
      electron transfer interaction with anilines in acetonitrile was obtained from
      transient spectral characterization of formed radicals. Experimental k(q) values
      approach the diffusion-controlled rate limit, and decrease significantly from DMT
      (1.85x10(10)M-1s-1) to DMABA (1.95x10(9)M-1s-1). These k(q) values depend on the
      charge density on the "N" atom of anilines, which could be quantified by Hammett
      sigma constant.

PMID- 16815084
TI  - Sulphate efflorescent minerals from El Jaroso Ravine, Sierra Almagrera--An SEM
      and Raman spectroscopic study.
AB  - Two sulphate efflorescent evaporite mineral samples from Jaroso, Spain have been
      studied by scanning electron microscopy and Raman spectroscopy. SEM by comparison
      with known minerals shows the evaporite mineral is a mixture of halotrichite and
      jarosite, whilst the oxidised mineral is predominantly jarosite. SEM
      characterises the halotrichite as long narrow crystals and the jarosite as
      distorted rhombohedral crystals. Raman spectra of the sulphates of K, Mg, Fe(II),
      Fe(III) are compared with the spectra of halotrichite, jarosite and the two
      sulphate efflorescent samples. The efflorescent sample was proven by Raman
      spectroscopy to be a mixture of halotrichite and jarosite and the oxidised
      efflorescent sample to be jarosite and a complex mixture of sulphates.

PMID- 16815085
TI  - FTIR spectroscopic characterization of polyurethane-urea model hard segments
      (PUUMHS) based on three diamine chain extenders.
AB  - Six polyurethane-urea model hard segments (PUUMHS) were prepared by a solution
      method based, respectively, on two isocyanates: 4,4'-methylene-diphenyl
      diisocyanate (MDI), 4,4'-methylene-dicyclohexyl diisocyanate (HMDI) and three
      amine chain extenders: ethylene diamine (EDA), methylene-bis-ortho-chloroaniline
      (MOCA), 2,4-diamino-3,5-dimethylsuphylchlorobenzene (DDSCB). FTIR was used to
      study their spectroscopic characterization. The main FTIR bands of the six
      samples were assigned and compared. It was found that most of N-H and C=O are H
      bonded in these PUUMHS. However, the N-H in three MDI based PUUMHS is all in the
      stronger H-bond state than that in their corresponding HMDI based while the C=O
      in three HMDI based PUUMHS is all in the stronger H-bond state than that in their
      corresponding MDI based, respectively. In addition, the order of the H-bond
      strength in HMDI based PUUMHS is MOCA, DDSCB and EDA whether according to nuN-H
      or nuC=O band wavenumbers, which is, however, different from that in MDI based
      PUUMHS. Moreover, the HMDI based PUUMHS shows obvious double amide III bands
      while the MDI based has only prominent one. The results are discussed according
      mainly to the different characteristics of the three chain extenders as well as
      the structure difference between MDI and HMDI.

PMID- 16815086
TI  - Vibrational spectra of the Cu(II) complexes of L-asparagine and L-glutamine.
AB  - The infrared and Raman spectra of the copper(II) complexes [Cu(L-asn)2] and [Cu(L
      gln)2] (L-asn=L-asparagine; L-gln=L-glutamine), were recorded and analyzed in
      relation to its structural peculiarities. Some comparisons between the spectra of
      these complexes and with those of related systems are made. The characteristics
      of the carboxylate and amide groups of the bonded ligands are discussed in
      detail.

PMID- 16815087
TI  - FTIR, FT-Raman spectra and ab initio, DFT vibrational analysis of 2,4
      dinitrophenylhydrazine.
AB  - The FTIR and FT-Raman spectra of 2,4-dinitrophenylhydrazine (2,4-DNPH) has been
      recorded in the region 4000-400 and 3500-50cm-1, respectively. The optimized
      geometry, frequency and intensity of the vibrational bands of 2,4-DNPH were
      obtained by the ab initio and density functional theory (DFT) levels of theory
      with complete relaxation in the potential energy surface using 6-31G(d,p) and 6
      311G(d,p) basis sets. The harmonic vibrational frequencies were calculated and
      the scaled values have been compared with experimental FTIR and FT-Raman spectra.
      The observed and the calculated frequencies are found to be in good agreement.
      The experimental spectra also coincide satisfactorily with those of theoretically
      constructed bar type spectrograms.

PMID- 16815088
TI  - Electron paramagnetic resonance, optical absorption and IR spectroscopic studies
      of the sulphate mineral apjohnite.
AB  - Apjohnite, a naturally occurring Mn-bearing pseudo-alum from Terlano, Bolzano,
      Italy, has been characterized by EPR, optical, IR and Raman spectroscopy. The
      optical spectrum exhibits a number of electronic bands around 400 nm due to
      Mn(II) ion in apjohnite. From EPR studies, the parameters derived, g=2.0 and
      A=8.82 mT, confirm MnO(H(2)O)(5) distorted octahedra. The presence of iron
      impurity in the mineral is reflected by a broad band centered around 8400 cm(-1)
      in the NIR spectrum. A complex band profile appears strongly both in IR and Raman
      spectra with four component bands around 1100 cm(-1) due to the reduction of
      symmetry for sulphate ion in the mineral. A strong pair of IR bands at 1681 and
      1619 cm(-1) with variable intensity is a proof for the presence of water in two
      states in the structure of apjohnite.

PMID- 16815089
TI  - Fluorescence quenching of 3-methyl 7-hydroxyl Coumarin in presence of acetone.
AB  - Fluorescence quenching of 3-methyl 7-hydroxyl Coumarin in prescence of the
      acetone is reported here. It was found that the quenching observed was of dynamic
      nature. It is also observed that quenching of the fluorescence of the indicator
      had a full reversiblity. As it has a full reversiblity, a novel optical sensor
      for acetone can be constructed on this quenching.

PMID- 16815090
TI  - Photophysical properties of novel lanthanide (Tb3+, Dy3+, Eu3+) complexes with
      long chain para-carboxyphenol ester p-L-benzoate (L=dodecanoyloxy, myristoyloxy,
      palmitoyloxy and stearoyloxy).
AB  - In this paper, a series of 12 binary luminescent lanthanide coordination
      compounds with long chain p-carboxyphenol ester were assembled. Both elemental
      analysis and infrared spectroscopy allowed to determine the complexes formula:
      LnL3, where Ln=Tb, Dy, Eu; L=p-dodecanoyloxybenzoate (12-OBA), p
      myristoyloxybenzoate (14-OBA), p-palmitoyloxybenzoate (16-OBA) and p
      stearoyloxybenzoate (18-OBA), respectively. The photophysical properties of these
      complexes were studied in detail with various of spectroscopies such as
      ultraviolet-visible absorption spectra, low temperature phosphorescence spectra
      and fluorescent spectra. The ultraviolet-visible absorption spectra showed that
      some bands shift with the different chain length of p-carboxyphenol ester. From
      the low temperature phosphorescent emission, the triplet state energies for these
      four ligands were determined to be around 24,242 cm-1 (12-OBA), 24,612 cm-1 (14
      OBA), 24,084 cm-1 (16-OBA) and 24,125 cm-1 (18-OBA), respectively, suggesting
      they are suitable for the sensitization of the above lanthanide ions, especially
      for Tb3+ and Dy3+. The fluorescence excitation and emission spectra for these
      lanthanide complexes of the four ligands take agreement with the above predict
      from energy match.

PMID- 16815091
TI  - Flow injection-chemiluminescence determination of phenol using potassium
      permanganate and formaldehyde system.
AB  - It is found that phenol can react with potassium permanganate in the acidic
      medium and produce chemiluminescence, which is greatly enhanced by formaldehyde.
      The optimum conditions for this chemiluminescent reaction are in detail studied
      using a flow injection system. The experiments indicate that under optimum
      conditions, the chemiluminescence intensity is linearly related to the
      concentration of phenol in the range 5.0x10(-9) to 1.0x10(-6)gmL-1 with a
      detection limit (3sigma) of 3x10(-9)gmL-1. The relative standard deviation is
      1.2% for 4.0x10(-7)gmL-1 phenol solution in 11 repeated measurements. This method
      has the advantages of simple operation, fast response and high sensitivity. The
      method is successfully applied to the determination of phenol in the waste water.

PMID- 16815092
TI  - Lung phospholipid metabolism in transgenic mice overexpressing peroxiredoxin 6.
AB  - Previous studies with peroxiredoxin 6 (Prdx6) null mice demonstrated that the
      phospholipase A(2) activity of this enzyme plays a major role in lung
      phospholipid metabolism. This study evaluated lung phospholipid metabolism in
      transgenic mice that over-express Prdx6. Lung lysosomal type PLA(2) activity in
      transgenic mice was 222% of wild type in lung homogenate and 280% in isolated
      lamellar bodies. Total phospholipid, phosphatidylcholine (PC) and disaturated PC
      were decreased approximately 20-35% in bronchoalveolar lung fluid, lung
      homogenate, and lung lamellar bodies in transgenic mice although lung compliance
      and type 2 cell ultrastructure were unaltered. To study metabolism, unilamellar
      liposomes ((3)H-DPPC: PC: cholesterol: PG, 10: 5: 3: 2 mol fraction) were
      instilled endotracheally in anesthetized mice and lungs were removed for
      perfusion. Compared to wild type, transgenic mice showed similar net uptake of
      liposomes in 2 h, but significantly increased (3)H-DPPC degradation (38.9+/-1.1
      vs. 29.0+/-1.3% of recovered dpm). The PLA(2) competitive inhibitor MJ33
      decreased degradation to 15% of recovered dpm in both transgenic and wild type
      lungs. Incorporation of [(14)C] palmitate into DSPC at 24 h after its intravenous
      injection was markedly increased in both the lung surfactant (+100%) and lamellar
      bodies (+188%) while incorporation of [(3)H] choline was increased by only 10
      20%. These results indicate increased DPPC degradation and synthesis by the
      reacylation pathway with Prdx6 overexpression and provide additional evidence
      that the PLA(2) activity of Prdx6 has an important role in lung surfactant
      turnover.

PMID- 16815093
TI  - Adiponectin plays an important role in efficient energy usage under energy
      shortage.
AB  - Adiponectin is an adipose tissue-specific secretory protein known to be an
      insulin-sensitizing protein. In this study, we generated adiponectin sense and
      antisense transgenic (Tg) mice to investigate whether adiponectin plays a role in
      the regulation of energy homeostasis during the growth stage. Spontaneous motor
      activity of antisense Tg mice were markedly reduced during fasting, particularly
      in young female mice, compared with wild type (Wt) and sense Tg mice.
      Furthermore, both body weight and adipose tissue mass of the antisense female Tg
      mice drastically reduced during fasting. To examine the relationship between the
      collapse of abdominal white adipose tissue (WAT) and serum adiponectin level, we
      measured the expression of genes related to energy expenditure, such as
      uncoupling protein (UCP). Notably, the mRNA of UCP1 in the WAT of antisense Tg
      female mice was markedly less than that of Wt mice and the UCP1 mRNA was strongly
      increased during fasting. These findings suggest that the serum adiponectin is
      important to maintaining energy homeostasis under energy shortage conditions,
      such as over female pubertal development.

PMID- 16815094
TI  - Cluster of Pseudomonas aeruginosa catheter-related bloodstream infections traced
      to contaminated multidose heparinized saline solutions in a medical ward.
AB  - Intravascular catheters are indispensable in modern medical practice; healthcare
      institutions purchase millions of them each year. The present study describes an
      outbreak of Pseudomonas aeruginosa catheter-related bloodstream infection (CRBSI)
      in a medical ward of the associated hospitals, a teaching hospital with 1005
      beds, in Ancona, Italy, with details of the source of infection and the efficacy
      of the control measures adopted. The environmental strain of P. aeruginosa was
      isolated from the mixture of heparin and saline solution. Clinical and
      environmental isolates were identical at PFGE, showing that the outbreak had been
      caused by a single clone of P. aeruginosa. The frequency of P. aeruginosa
      bacteraemia depends on the population of patients studied; our patients did not
      show risk factors that increased their susceptibility to hospital infections. As
      these pathogens cannot be eradicated from the hospital environment, constant
      infection control measures are needed in order to prevent nosocomial infections.

PMID- 16815095
TI  - The impact of new guidelines in Europe for the control and prevention of travel
      associated Legionnaires' disease.
AB  - On 1 July 2002, EWGLINET introduced European guidelines for the control and
      prevention of travel-associated legionnaires' disease. This paper presents the
      results gathered by the surveillance scheme during the first two and a half years
      of the operation of the guidelines (to the end of 2004). Two hundred and thirty
      seven new clusters and 70 cluster updates were identified. Investigations at 146
      sites returned positive samples for legionella, and the proportion of positive
      sites reached over 60% in 2004. Thirty-four cluster sites were reported to have
      been investigated satisfactorily, but have gone on to be associated with
      subsequent cases ('repeater sites'). Fifty-one sites were published on the
      European Working Group for Legionella Infections (EWGLI) website; the publication
      states that EWGLINET cannot be confident that the sites have adequate control
      measures in place. The operation of the guidelines is discussed, and the
      situation in Turkey highlighted as a particular success.

PMID- 16815096
TI  - Protective efficacy of recombinant (Ag85A) BCG Tokyo with Ag85A peptide boosting
      against Mycobacterium tuberculosis-infected guinea pigs in comparison with that
      of DNA vaccine encoding Ag85A.
AB  - A recombinant form of BCG Tokyo with an Ag85A gene insert was administered once
      subcutaneously to guinea pigs and its protective efficacy was compared with that
      of a DNA vaccine encoding Ag85A from Mycobacterium tuberculosis administered
      twice to guinea pigs by epidermal gene gun bombardment. Vaccination with either
      the recombinant BCG Tokyo or Ag85A DNA significantly reduced the severity of
      pulmonary pathology and the number of pulmonary and splenic colony-forming units
      (cfu) (p<0.001). The recombinant BCG Tokyo was better than Ag85A DNA in terms of
      protective efficacy against M. tuberculosis. When immunogenic synthetic Ag85A
      peptide was further used as a booster together with recombinant BCG Tokyo (Ag85A)
      or Ag85A DNA, lung pathology was improved significantly and the number of
      pulmonary CFU was reduced significantly. Neither recombinant BCG Tokyo, Ag85A
      DNA, nor the parental BCG Tokyo protected the guinea pigs from hematogenous
      spread of tubercle bacilli to the spleen because splenic granulomas without
      central necrosis were recognized. The spleen tissues from guinea pigs vaccinated
      with recombinant BCG Tokyo or Ag85A DNA expressed IFN-gamma and IL-2 mRNA at
      significantly high levels (p<0.001) as evaluated by reverse transcription
      polymerase chain reaction. It is concluded that peptide boosting is important for
      the induction of higher protective efficacy by recombinant BCG Tokyo or a
      tuberculosis DNA vaccine and both recombinant BCG Tokyo (Ag85A) and Ag85A DNA
      vaccine induce Th2 cytokine mRNA expression significantly.

PMID- 16815098
TI  - Expression of the basic helix-loop-factor Olig2 in the developing retina: Olig2
      as a new marker for retinal progenitors and late-born cells.
AB  - In this study, we examined the spatiotemporal expression patterns of Olig2, a
      basic helix-loop-helix transcription factor, in the developing mouse retina.
      Expression of Olig2 was initially detected on embryonic day 12.5 (E12.5). The
      majority of Olig2-positive cells were identified as retinal progenitor cells
      throughout embryogenesis. During later embryonic stages, the number of Olig2
      positive retinal progenitor cells increased, and Olig2-positive cells were
      confined only to the neuroblast layer (NBL). Olig2 expression was not observed in
      the ganglion cell layer (GCL) nor in the inner nuclear layer (INL) that contain
      the differentiated retinal cell types, indicating that Olig2 is not expressed in
      differentiated cells in prenatal retina. In later postnatal stages, Olig2
      expression was retained in mature neurons and glial cells, namely retinal
      ganglion cells (RGCs), amacrine cells (ACs), horizontal cells, bipolar cells and
      Muller glial cells. Thus, Olig2 is an marker both for retinal progenitor cells
      during embryonic stages, and also for differentiated retinal subpopulations
      within the GCL and INL during postnatal stages.

PMID- 16815099
TI  - Murine embryonic expression of the gene for the UV-responsive protein p15(PAF).
AB  - In a screen for genes expressed in the embryonic mouse facial primordia, we
      identified the gene sequence annotated as KIAA0101, which has previously been
      shown to encode a novel proliferating cell nuclear antigen (PCNA)-interacting
      protein named p15(PAF). We have since demonstrated that this protein also
      interacts in a complex with the tumour suppressor product p33ING1b, and that
      overexpression results in a decrease in UV-induced cell death. Although available
      data suggest widespread or ubiquitous expression in the adult, here we report
      highly restricted expression of the p15(PAF) gene in a spatio-temporal manner
      during mouse embryogenesis. Major sites of expression include the facial
      prominences, limbs, somites, brain, spinal cord and hair follicles. Based on the
      nature of its interacting partners, p15(PAF) is proposed to play a role in
      tumorigenesis. Our data also suggest a role in embryonic development, consistent
      with findings that a wide range of tumours result from aberrant activity of key
      developmental pathways.

PMID- 16815100
TI  - Characterization of the zebrafish matrix metalloproteinase 9 gene and its
      developmental expression pattern.
AB  - Members of the matrix metalloproteinase (MMP) family are important for the
      remodeling of the extracellular matrix in a number of biological processes
      including a variety of immune responses. Two members of the family, MMP2 and
      MMP9, are highly expressed in specific myeloid cell populations in which they
      play a role in the innate immune response. To further expand the repertoire of
      molecular reagents available to study zebrafish myeloid cell development, the
      matrix metalloproteinase 9 (mmp9) gene from this organism has been identified and
      characterized. The encoded protein is 680 amino acids with high homology to known
      MMP9 proteins, particularly those of other teleost fish. Maternal transcripts of
      mmp9 are deposited in the oocyte and dispersed throughout the early embryo. These
      are replaced by specific zygotic transcripts in the notochord from 12h post
      fertilization (hpf) and also transiently in the anterior mesoderm from 14 to 16h
      post fertilization. From 24h post fertilization, mmp9 expression was detected in
      a population of circulating white blood cells that are distinct from macrophages,
      and which migrate to the site of trauma, and so likely represent zebrafish
      heterophils. In the adult, mmp9 expression was most prominent in the splenic
      cords, a site occupied by mature myeloid cells in other species. These results
      suggest that mmp9 will serve as a useful marker of mature myeloid cells in the
      zebrafish.

PMID- 16815101
TI  - Is insulin resistance atherogenic? Possible mechanisms.

PMID- 16815102
TI  - Mitochondrial disease activates transcripts of the unfolded protein response and
      cell cycle and inhibits vesicular secretion and oligodendrocyte-specific
      transcripts.
AB  - Mutations in gene products expressed in the mitochondrion cause a nuclear
      transcriptional response that leads to neurological disease. To examine the
      extent to which the transcriptional profile was shared among 5 mitochondrial
      diseases (LHON, FRDA, MELAS, KSS, and NARP), we microarrayed mutant and control
      groups in N-tera2, SH-SY5Y, lymphoblasts, fibroblasts, myoblasts, muscle, and
      osteosarcoma cybrids. Many more transcripts were observed to be significantly
      altered and shared among these 5 mitochondrial diseases and cell types than
      expected on the basis of random chance, and these genes are significantly
      clustered with respect to biochemical pathways. Mitochondrial disease activated
      multiple transcripts of the unfolded protein response (UPR), and of the cell
      cycle pathway, and low doses of the mitochondrial inhibitor rotenone induced UPR
      transcripts in the absence of cell death. By contrast, functional clusters
      inhibited by mitochondrial disease included: vesicular secretion, protein
      synthesis, and oligodendrogenesis. As it is known that UPR activation
      specifically inhibits vesicular secretion and protein synthesis, these data
      support the view that mitochondrial disease and dysfunction triggers the UPR,
      which in turn causes secretory defects which inhibit cellular migratory,
      synaptic, and oligodendrocytic functions, providing a testable hypothesis for how
      mitochondrial dysfunction causes disease. Since ischemic hypoxia, chemical
      hypoxia, and mitochondrial genetic disease (which could be considered 'genetic
      hypoxia') produce an overlapping induction of UPR and cell cycle genes which
      appears to have negative consequences, the modulation of these responses might be
      of benefit to patients with mitochondrial disease.

PMID- 16815103
TI  - The Fanconi anemia pathway limits the severity of mutagenesis.
AB  - Fanconi anemia (FA) is a developmental and cancer predisposition disorder in
      which key, yet unknown, physiological events promoting chromosome stability are
      compromised. FA cells exhibit excess metaphase chromatid breaks and are
      universally hypersensitive to DNA interstrand crosslinking agents. Published
      mutagenesis data from single-gene mutation assays show both increased and
      decreased mutation frequencies in FA cells. In this review we discuss the data
      from the literature and from our isogenic fancg knockout hamster CHO cells, and
      interpret these data within the framework of a molecular model that accommodates
      these seemingly divergent observations. In FA cells, reduced rates of recovery of
      viable X-linked hypoxanthine phosphoribosyltransferase (hprt) mutants are
      characteristically observed for diverse mutagenic agents, but also in untreated
      cultures, indicating the relevance of the FA pathway for processing assorted DNA
      lesions. We ascribe these reductions to: (1) impaired mutagenic translesion
      synthesis within hprt during DNA replication and (2) lethality of mutant cells
      following replication fork breakage on the X chromosome, caused by unrepaired
      double-strand breaks or large deletions/translocations encompassing essential
      genes flanking hprt. These findings, along with studies showing increased
      spontaneous mutability of FA cells at two autosomal loci, support a model in
      which FA proteins promote both translesion synthesis at replication-blocking
      lesions and repair of broken replication forks by homologous recombination and
      DNA end joining. The essence of this model is that the FANC protein pathway
      serves to restrict the severity of mutational outcome by favoring base
      substitutions and small deletions over larger deletions and chromosomal
      rearrangements.

PMID- 16815104
TI  - Modeling oncogenic translocations: distinct roles for double-strand break repair
      pathways in translocation formation in mammalian cells.
AB  - Reciprocal chromosomal translocations are implicated in the etiology of many
      tumors, including leukemias, lymphomas, and sarcomas. DNA double-strand breaks
      (DSBs) caused by various cellular processes and exogenous agents are thought to
      be responsible for the generation of most translocations. Mammalian cells have
      multiple pathways for repairing DSBs in the chromosomes: non-homologous end
      joining (NHEJ), homologous recombination (HR), and single-strand annealing (SSA),
      which is a specialized pathway involving sequence repeats. In this review, we
      summarize the various reporters that have been used to examine the potential for
      each of these DSB repair pathways to mediate translocation formation in mammalian
      cells. This approach has demonstrated that NHEJ is very proficient at mediating
      translocation formation, while HR is not because of crossover suppression.
      Although SSA can efficiently mediate translocations between identical repeats,
      its contribution to translocation formation is likely very limited because of
      sequence divergence between repetitive elements in the genome.

PMID- 16815106
TI  - Ventilatory responses to isocapnic and poikilocapnic hypoxia in humans.
AB  - We examined the hypoxic ventilatory response (HVR) including breathing frequency
      (f(R)) and tidal volume (V(T)) responses during 20 min of step isocapnic (IH) and
      poikilocapnic (PH) hypoxia (45 Torr). We hypothesized an index related to
      [Formula: see text] (pHPR) may be more robust during PH. Peak HVR was suppressed
      during PH (P<0.001), and mediated by V(T) during PH and both V(T) and f(R) during
      IH. The relative magnitude of HVD remained similar between conditions indicating
      a suppressive role of hypocapnia in development of the HVR unrelated to the
      degree of subsequent HVD, implying a primarily O(2) dependant mechanism. Post
      hypoxic frequency decline was observed following both IH (3.4+/-3.7 bpm, P<0.05)
      and PH (3.6+/-3.1 bpm, P<0.01), despite no f(R) response during exposure to PH.
      Use of pHPR improved the signal to noise ratio during PH, though failed to detect
      the peak ventilatory response, and therefore may not be appropriate when
      describing peak responses.

PMID- 16815105
TI  - Myc translocations in B cell and plasma cell neoplasms.
AB  - Chromosomal translocations that join the cellular oncogene Myc (c-myc) with
      immunoglobulin (Ig) heavy-chain (Igh) or light-chain (Igk, Igl) loci are widely
      believed to be the crucial initiating oncogenic events in the development of B
      cell and plasma cell neoplasms in three mammalian species: Burkitt lymphoma (BL)
      in human beings, plasmacytoma (PCT) in mice, and immunocytoma in rats. Among the
      Myc-Ig translocations found in these neoplasms, mouse PCT T(12;15)(Igh-Myc) is of
      special interest because it affords a uniquely useful model system to study the
      fundamental outstanding questions on the mechanisms, genetics, and biological
      consequences of Myc translocations. Mouse T(12;15) is the direct counterpart of
      the human BL t(8;14)(q24;q32) translocation and thus of great relevance for human
      cancer. Mouse T(12;15) is the only cancer-associated translocation in mice that
      occurs with high incidence, spontaneity, and cell-type specificity. Due to the
      development of PCR methods for the detection of the underlying reciprocal Myc-Igh
      junction fragments, it is now known that mouse T(12;15) can be a dynamic process
      that begins with the genetic exchange of Myc and the Igh switch mu region (Smu),
      progresses by class switch recombination (CSR) just 3' of the translocation break
      site, and then undergoes further clonal diversification by micro-deletions in the
      junction flanks. The molecular pathway that subverts CSR to mediate trans
      chromosomal joining of Myc and Smu (translocation origin) and secondary
      modification of Myc-Igh junctions (translocation "remodeling") has not been
      elucidated, but recent evidence indicates that it includes CSR factors, such as
      the activation-induced cytidine deaminase (AID), that may also be involved in the
      ongoing neoplastic progression of the translocation-bearing tumor precursor.
      Transgenic mouse models of T(12;15)/t(8;14), including newly developed "iMyc"
      gene-insertion mice, will be useful in elucidating the role of these CSR factors
      in the progression of Myc-induced B cell tumors.

PMID- 16815107
TI  - High-performance liquid chromatographic method for the determination of
      pioglitazone in human plasma using ultraviolet detection and its application to a
      pharmacokinetic study.
AB  - An analytical method based on high-performance liquid chromatography (HPLC) with
      ultraviolet detection (269 nm) was developed for the determination of
      pioglitazone in human plasma. Rosiglitazone was used as an internal standard.
      Chromatographic separation was achieved with a reversed-phase Apollo C18 column
      and a mobile phase of methanol-acetonitrile-mixed phosphate buffer (pH 2.6; 10mM)
      (40:12:48, v/v/v) with a flow rate of 1.2 ml/min. The calibration curve was
      linear over the range of 50-2000 ng/ml (r(2)>0.9987) and the lower limit of
      quantification was 50 ng/ml. The method was validated with excellent sensitivity,
      accuracy, precision, recovery and stability. The assay has been applied
      successfully to a pharmacokinetic study with human volunteers.

PMID- 16815111
TI  - Availability of nutrition information on menus at major chain table-service
      restaurants.

PMID- 16815112
TI  - Cooking with soul: a look into faith-based wellness programs: interview conducted
      by Tony Peregrin.

PMID- 16815113
TI  - Good or bad: what you see isn't always what you get.

PMID- 16815114
TI  - Ethics opinion: conflict of interest disclosure on listservs.

PMID- 16815115
TI  - Shaping the marketplace for medical nutrition therapy -- advocating for coverage.

PMID- 16815117
TI  - Is the only outcome that counts related to registered dietitians'
      recommendations?

PMID- 16815118
TI  - Is calcium and vitamin D supplementation overrated?

PMID- 16815119
TI  - Stage of change for healthful eating and use of behavioral strategies.
AB  - OBJECTIVE: To examine the distribution of behavioral strategy use across stage of
      change for healthful eating, and to determine if baseline stage predicts change
      in use of strategies over 1 year in the absence of intervention. DESIGN: Cross
      sectional assessment and 1-year follow-up with no intervention. SUBJECTS/SETTING:
      Adult men and women in two rural Midwest communities. STATISTICAL ANALYSES
      PERFORMED: Multiple regression, with tests for group difference and trend,
      controlling for age and sex. RESULTS: Use of behavioral strategies as measured by
      six scales (self-monitoring, planning, preparation and buying, portion control,
      social interactions, and cognitive strategies) followed a clear linear trend
      across stages of change for healthful eating. Strategy use was more strongly
      related to stage than energy intake, fat intake, and fruit and vegetable servings
      as measured via food frequency questionnaire. Baseline stage of change showed
      some relationship to change in strategy use over time, although most group
      differences were not statistically significant. CONCLUSIONS: Use of a range of
      behavioral strategies is strongly related to stage of change for healthful
      eating, and more closely associated with stage than dietary intake. In the
      absence of intervention, baseline stage only weakly predicted changes in strategy
      use. Programs with the goal of encouraging a range of healthful eating behaviors
      may find these measures of strategy use to be helpful in defining stage of
      change, and possibly in tracking behavior change over time.

PMID- 16815120
TI  - Meal programs improve nutritional risk: a longitudinal analysis of community
      living seniors.
AB  - OBJECTIVE: To determine the independent association of meal programs (eg, Meals
      On Wheels and other meal programs with a social component) and shopping help on
      seniors' nutritional risk. DESIGN: Cohort design. Baseline data were collected
      with an in-person interview and subjects were followed up for 18 months via
      telephone interview. SUBJECTS/SETTING: Cognitively well, vulnerable (ie, required
      informal or formal supports for activities of daily living) seniors were
      recruited through community service agencies in southwestern Ontario, Canada.
      Three hundred sixty-seven seniors participated in baseline interviews and 263
      completed data collection at 18-month follow-up; 70% participated in meal
      programs at baseline. MAIN OUTCOME MEASURES: The 15-item Seniors in the
      Community: Risk Evaluation for Eating and Nutrition (SCREEN) questionnaire
      identified nutritional risk at 18 months. STATISTICAL ANALYSES PERFORMED:
      Descriptive and bivariate analyses were performed and significant associations
      (P<0.05) used to build the full multiple linear regression model. Meal and
      shopping variables were forced into the model as predictors of follow-up SCREEN
      questionnaire scores. RESULTS: Meals On Wheels use was independently associated
      with higher SCREEN questionnaire scores (ie, less risk), as was higher income.
      Baseline SCREEN questionnaire scores also strongly and positively predicted
      follow-up scores. Self-reported depression at baseline was associated with lower
      scores at follow-up. Although use of programs at baseline was associated with
      decreased risk, if participants experienced increased use of the program (eg,
      more meals) during the follow-up period this was associated with lower scores, or
      increased risk. CONCLUSIONS: Meal programs can improve or maintain nutritional
      risk for vulnerable seniors. Increased use of these programs over time may
      indicate a senior's declining status. Seniors who are in need of informal or
      formal supports for food shopping or preparation should be encouraged to
      participate in meal programs as a means of maintaining or improving their
      nutrition.

PMID- 16815121
TI  - Sensory characteristics of beverages prepared with commercial thickeners used for
      dysphagia diets.
AB  - OBJECTIVE: To describe and compare sensory characteristics of six beverages
      prepared with four commercial thickeners used in dysphagia diets. DESIGN: The
      study used a completely randomized design within a test of each beverage.
      SUBJECTS/SETTING: Five highly trained descriptive sensory analysis panelists
      conducted the testing in a laboratory environment. INTERVENTION: Coffee, milk,
      apple juice, orange juice, Ensure (Abbott Laboratories, Abbott Park, IL), and
      water were thickened using two starch-based and two gum-based commercial
      thickeners according to manufacturers' instructions to achieve nectar-like and
      honey-like consistencies. MAIN OUTCOME MEASURES: Sensory attributes of the
      original beverages and the thickened samples were defined and scored. STATISTICAL
      ANALYSES PERFORMED: Sensory scores were analyzed by analysis of variance using
      general linear models and Fisher's least significant difference test to determine
      specific differences. RESULTS: All thickeners suppressed the main flavors of the
      base beverages and imparted slight off-flavors (bitter, sour, metallic, or
      astringent) in some beverages. Starch-based thickeners imparted a starchy flavor
      and grainy texture, whereas gum-based thickeners gave added slickness to the
      beverages. Although thickeners mixed well with some beverages, they were
      difficult to disperse in others, making some thickened beverages lumpy.
      CONCLUSIONS: All thickeners added either a starchy, grainy, or slick flavor or
      texture and tended to suppress the base flavor of beverages, especially at honey
      like consistencies. Thus, individual decisions about which characteristics are
      more negative (eg, slick vs grainy texture) for specific patients must be made.
      Additional development of thickening agents seems necessary for improved sensory
      properties. Information from this article should help professionals and their
      patients with dysphagia better understand the sensory issues associated with the
      use of commercial thickening agents in various beverages.

PMID- 16815122
TI  - Diet quality among Yup'ik Eskimos living in rural communities is low: the Center
      for Alaska Native Health Research Pilot Study.
AB  - OBJECTIVE: The objectives of this pilot study were to describe the nutrient
      intake of Yup'ik Eskimos in comparison with national intake, identify dietary
      sources of key nutrients, and assess the utility of the Healthy Eating Index
      (HEI) to measure diet quality of Yup'ik Eskimos living in rural Alaskan Native
      communities. PARTICIPANTS AND DESIGN: A single 24-hour recall was collected from
      48 male and 44 female Yup'ik Eskimos (aged 14 to 81 years), who resided in three
      villages in the Yukon Kuskokwim River Delta, AK, during September 2003. MAIN
      OUTCOME MEASURES: HEI scores, nutrient intake, and traditional food intake.
      STATISTICAL ANALYSES PERFORMED: Spearman correlations for associations between
      variables. RESULTS: Youth scored higher than elders despite similar nutrient
      intakes. Overall diet quality was generally low; 63% of all participants' diets
      were classified as poor. Although the HEI serves to identify areas of concern
      with respect to diet quality, it is limited in its ability to detect the positive
      value of traditional foods. CONCLUSIONS: Traditional foods and healthful market
      foods, including rich sources of fiber and calcium, should be encouraged.
      Although traditional foods were important sources of energy and nutrients, market
      foods composed the preponderance of the diet, emphasizing the importance of
      appropriately modifying a diet quality index based on a Western framework, such
      as the HEI.

PMID- 16815123
TI  - Calcium intake and 10-year weight change in middle-aged adults.
AB  - OBJECTIVE: The goal of this study was to examine the purported effects of calcium
      on modulating body weight. DESIGN: Retrospective data was used to assess the
      relationship between calcium intake and weight change over an 8- to 12-year
      period among middle-aged adults. SUBJECTS: Participants were 10,591 men and women
      aged 53 to 57 years recruited during 2000-2002. STATISTICAL ANALYSIS: Linear
      regression was used to model associations of 10-year weight change and calcium
      intake, adjusted for weight at age 45 years, energy intake, physical activity,
      and other factors. RESULTS: Calcium intake was associated with 10-year weight
      change only in women. Women with current calcium supplement dose of >500 mg/day
      had a 10-year weight gain of 5.1 kg (95% confidence interval 4.7 to 5.5) compared
      to 6.9 kg (95% confidence interval 6.5 to 7.4) among nonusers (P for
      trend=0.001). Trends were similar for total calcium intake from diet plus
      supplements (P for trend=0.001). Dietary calcium alone had no significant effect
      on 10-year weight change. CONCLUSIONS: Increasing total calcium intake, in the
      form of calcium supplementation, may be beneficial to weight maintenance,
      especially in women during midlife.

PMID- 16815124
TI  - Nutrigenetics, plasma lipids, and cardiovascular risk.
AB  - Cardiovascular disease (CVD) results from complex interactions between genetic
      and environmental factors. The evidence supports that gene-environment
      interactions modulate plasma lipid concentrations and potentially CVD risk.
      Several genes (eg, apolipoprotein A-I and A-IV, apolipoprotein E, and hepatic
      lipase) are providing proof-of-concept for the application of genetics in the
      context of personalized nutrition for CVD prevention. The spectrum of candidate
      genes has been expanding to incorporate those involved in intracellular lipid
      metabolism and especially those transcription factors (ie, peroxisome
      proliferator activator receptors) that act as sensors of nutrients in the cell
      (eg, polyunsaturated fatty acids) to trigger metabolic responses through
      activation of specific sets of genes. However, current knowledge is still very
      limited and so is the potential benefit of its application to clinical practice.
      Thinking needs to evolve from simple scenarios (eg, one single dietary component,
      a single nucleotide polymorphism and risk factor) to more realistic situations
      involving multiple interactions. One of the first situations where personalized
      nutrition is likely to be beneficial is in patients with dyslipidemia who require
      special intervention with dietary treatment. This process could be more efficient
      if the recommendations were carried out based on genetic and molecular knowledge.
      Moreover, adherence to dietary advice may increase when it is supported with
      information based on nutritional genomics, and a patient believes the advice is
      personalized. However, a number of important changes in the provision of health
      care are needed to achieve the potential benefits associated with this concept,
      including a teamwork approach with greater integration among physicians, food and
      nutrition professionals, and genetic counselors.

PMID- 16815125
TI  - Eating disorder nutrition counseling: strategies and education needs of English
      speaking dietitians in Canada.
AB  - The purpose of this study was to profile nutrition counseling strategies for
      eating disorders that English-speaking Canadian registered dietitians (RDs) use
      and to explore their educational needs in this area. A cross-sectional survey
      consisting of open- and closed-ended questions on nutrition counseling strategies
      was developed and administered via mail. Types of strategies included assessment,
      rapport-building, educational, and behavior-change strategies. Sixty-five of the
      116 eligible RDs who were members of the Dietitians of Canada Eating Disorder
      Network responded to the survey. Descriptive statistics, chi(2), and Spearman
      correlation statistics were used. P values less than 0.05 were considered
      significant. Canadian RDs used strategies that were familiar and strategies they
      considered useful. Content-oriented or "doing" strategies were used more often
      than strategies that involved some process-oriented or "thinking" strategies.
      Reading and intuition were the most frequently reported learning routes. Seventy
      one percent of respondents were dissatisfied with the educational opportunities
      available to RDs in this area in Canada. In Canada, both generalist RDs and
      specialist eating disorders RDs work with clients with eating disorders. In the
      absence of a formal nutrition counseling education program, there seems to be a
      reliance on informal learning routes such as reading or intuition, which may be
      suboptimal. To optimize eating disorders nutrition practice in Canada, formal
      coordinated programming that accounts for the educational needs of specialist RDs
      as well as generalist RDs is needed.

PMID- 16815127
TI  - Older black women differ in calcium intake source compared to age- and
      socioeconomic status-matched white women.
AB  - Racial disparity in osteoporosis between older black and white women is well
      established; however, less is known regarding daily dietary and supplemental
      calcium intake in these populations. Moreover, racial differences in calcium
      intake are confounded by differences in socioeconomic status (SES). The objective
      of this study was to assess calcium intake and source in older black women (n=33)
      and white women (n=33), matched in age and SES. Calcium intake and source were
      evaluated by interview using a 46-item calcium food frequency questionnaire
      including all food groups and supplements. Black and white women were identical
      in SES and matched on age (black women 66.9+/-6.2 years vs white women 67.1+/-5.5
      years [mean+/-standard deviation], P=0.85). No significant difference existed for
      dietary calcium intake between black and white women (974+/-524 vs 1,070+/-600
      mg/day; P=0.65) or total calcium intake between black and white women (1,485+/
      979 vs 1,791+/-887 mg/day; P=0.15). Dairy foods contributed most to dietary
      calcium intake in black and white women and differed by race (black women 402+/
      269 mg/day, white women, 603+/-376 mg/day; P=0.02). Calcium intake from grains
      differed by race (black women 205+/-201 mg/day vs white women 130+/-234 mg/day;
      P=0.010) and fortified cereals were a major source of calcium for black women.
      Calcium supplementation contributed substantially to total calcium intake in both
      groups, with more white women (n=23, 70%) using supplements than black women did
      (n=19, 58%). However, no racial difference existed in supplemented calcium intake
      (black women, n=19; 889+/-605 vs white women, n=23; 1,034+/-460 mg/day; P=0.20).
      Our data suggest that total daily dietary and supplemental calcium intakes do not
      differ, but calcium intake from dairy foods and from grains differ in older black
      and white women matched in age and SES.

PMID- 16815126
TI  - Eating restraint is negatively associated with biomarkers of bone turnover but
      not measurements of bone mineral density in young women.
AB  - Relationships among bone mineral density (BMD), bone turnover markers, cortisol,
      calcium and vitamin D intakes, and cognitive eating restraint score were
      examined. Sixty-five healthy women, ages 18 to 25 years, had total body, spine,
      hip, and forearm BMD measured by dual-energy x-ray absorptiometry. Serum
      osteocalcin, urinary cross-linked N-telopeptide of type I collagen (NTx), and
      salivary cortisol were measured, and intakes of calcium and vitamin D were
      estimated from questionnaires. Cognitive eating restraint scores were determined
      from the Eating Inventory. Associations between measures were analyzed by Pearson
      correlations; predictors of BMD and bone turnover markers were tested using
      stepwise regression. Serum osteocalcin (P<0.01) and urinary NTx (P<0.05) were
      negatively related to cognitive eating restraint score. Intakes of calcium
      (P<0.05) and vitamin D (P<0.05) were associated with forearm BMD. Regression
      analyses indicated that vitamin D intake predicted total body (P<0.08) and
      forearm (P<0.01) BMD. Negative associations between cognitive eating restraint
      score and bone biomarkers suggest a reduction in bone remodeling, not reflected
      in current BMD.

PMID- 16815128
TI  - Nutrition information sources vary with education level in a population of older
      adults.
AB  - Education level, more than any other socioeconomic factor, can predict disease
      risk, health behavior patterns, and diet quality. It has been suggested that one
      reason higher education promotes more healthful diets is that better-educated
      people may get better nutrition information. We present data from a survey
      examining specific sources of nutrition information among an older adult
      population (age >50 years, n=176), and compare the difference in sources
      associated with extent of education. Reliance on doctors, television, and
      neighbors was significantly higher among those with less education (P<0.05). Our
      results also show that less-educated older adults rely more upon different
      specific sources for their nutrition information than those who have attained a
      higher level of education. Strategies to improve and/or ensure the quality of the
      specific nutrition information sources this vulnerable group relies on may be
      needed.

PMID- 16815129
TI  - Oral condition and its relationship to nutritional status in the
      institutionalized elderly population.
AB  - The objective of this study was to identify the relationship between the oral
      condition and nutritional status of all institutionalized elderly people in
      Florianopolis, Brazil. Of the population of 232 institutionalized individuals,
      the sample consisted of 187 elderly people. In the oral evaluation, the criteria
      used was the number of functional units present in the oral cavity, classifying
      the participants as those with highly compromised dentition (48%) and those with
      less-compromised dentition (52%). Diagnosis of nutritional status was carried out
      according to body mass index, observing a prevalence of 14% thin, 45% eutrophic,
      28% overweight, and 13% obese. Statistical analysis of the variables studied was
      carried out by means of chi(2) association tests. There was a statistically
      significant association between highly compromised dentition and thinness
      (P=0.007) and among those who presented less-compromised dentition and the
      nutritional status of overweight, including obesity (P=0.014). It was concluded
      that compromising of the teeth could contribute to a tendency toward inadequate
      nutritional status.

PMID- 16815130
TI  - Provision of small, frequent meals does not improve energy intake of elderly
      residents with dysphagia who live in an extended-care facility.
AB  - Malnutrition and dehydration are potential consequences of dysphagia, a common
      swallowing disorder among elderly individuals. Providing smaller, more frequent
      meals has been suggested (but not demonstrated) to improve energy intake among
      this group. Accordingly, this study was designed to assess whether the same
      energy content in five vs three daily meals would improve energy intake. Thirty
      seven residents of an extended-care facility, aged older than 65 years,
      previously evaluated for dysphagia, and receiving a texture-modified diet, agreed
      to participate in a crossover study with random assignment to three or five meals
      during an initial 4-day study period, followed by the opposite meal pattern in a
      second period. Six were excluded from analysis, as their medical condition
      deteriorated before or during the study. Food and fluids consumed by participants
      during each study period were weighed before and after each meal. Average energy
      intakes were similar between the three- and five-meal patterns (1,325+/-207
      kcal/day vs 1,342+/-177 kcal/day, respectively; P=0.565); fluid intake was higher
      with five meals (698+/-156 mL/day) vs three (612+/-176 mL/day; P=0.003). Because
      offering five daily feedings did not improve energy intakes when compared with
      three, dietitians caring for this vulnerable group might need to consider other
      nutrition intervention strategies.

PMID- 16815131
TI  - Moving beyond the clinic: nutritional intervention in a human immunodeficiency
      virus-infected pregnant population.

PMID- 16815133
TI  - New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene
      environment interactions.
AB  - Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder in
      which genetic mutations and cutaneous hyperreactivity to environmental stimuli
      play a causative role. Genetic mutations alone might not be enough to cause
      clinical manifestations of AD, and this review will propose a new perspective on
      the importance of epidermal barrier dysfunction in genetically predisposed
      individuals, predisposing them to the harmful effects of environmental agents.
      The skin barrier is known to be damaged in patients with AD, both in acute
      eczematous lesions and also in clinically unaffected skin. Skin barrier function
      can be impaired first by a genetic predisposition to produce increased levels of
      stratum corneum chymotryptic enzyme. This protease enzyme causes premature
      breakdown of corneodesmosomes, leading to impairment of the epidermal barrier.
      The addition of environmental interactions, such as washing with soap and
      detergents, or long-term application of topical corticosteroids can further
      increase production of stratum corneum chymotryptic enzyme and impair epidermal
      barrier function. The epidermal barrier can also be damaged by exogenous
      proteases from house dust mites and Staphylococcus aureus. One or more of these
      factors in combination might lead to a defective barrier, thereby increasing the
      risk of allergen penetration and succeeding inflammatory reaction, thus
      contributing to exacerbations of this disease.

PMID- 16815134
TI  - The genetics of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic itching (pruritic) skin disease. It results
      from a complex interplay between strong genetic and environmental factors. Genome
      screens of families with AD have implicated chromosomal regions that overlap with
      other skin diseases and with inflammatory and autoimmune diseases. These,
      together with candidate gene studies, provide novel insights into the
      pathogenesis of AD. The findings suggest a common theme of generalized epidermal
      dysfunction manifesting as a compromised skin barrier and failure to protect
      against, or aberrant responses to, microbial insults and antigens. Recent genetic
      advances with high-throughput methods for gene identification, such as DNA
      microarrays and whole-genome genotyping, will help further dissect this complex
      trait. This will aid disease-defining criteria and focused therapies for AD.

PMID- 16815136
TI  - Atopic dermatitis.

PMID- 16815137
TI  - Control of airway inflammation maintained at a lower steroid dose with 100/50
      microg of fluticasone propionate/salmeterol.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) have been shown to reverse epithelial
      damage and decrease lamina reticularis thickness in patients with asthma.
      OBJECTIVE: This study investigated whether clinical asthma control and airway
      inflammation could be maintained after switching therapy from medium-dose
      fluticasone propionate (FP) to low-dose FP administered with the long-acting
      beta2-agonist (LABA) salmeterol. METHODS: Eighty-eight subjects (age, > or =18
      years) who, during open-label screening, demonstrated improved asthma control
      after an increase from 100 microg of FP twice daily to 250 microg of FP twice
      daily were randomized to receive 100/50 microg of FP/salmeterol through a Diskus
      inhaler (GlaxoSmithKline, Research Triangle Park, NC) twice daily or continue 250
      microg of FP twice daily through a Diskus inhaler for 24 weeks. Clinical outcomes
      were monitored, and bronchial biopsy specimens and bronchoalveolar lavage fluid
      were obtained before and after 24 weeks of treatment. RESULTS: There were no
      significant differences between treatments with respect to eosinophils in the
      bronchial mucosa and bronchoalveolar lavage fluid; mucosal mast cells,
      neutrophils, or CD3+, CD4+, CD8+, or CD25+ T lymphocytes; or concentration of
      mediators (GM-CSF, IL-8, and eosinophil cationic protein). The 2 treatments were
      not different with respect to lamina reticularis thickness. Consistent with the
      airway inflammatory measures, clinical and physiologic measures of asthma control
      were also similar. CONCLUSION: This study demonstrates that control of asthma and
      airway inflammation is maintained over the 24-week treatment period when patients
      requiring a medium-dose ICS are switched to a lower-dose ICS with a LABA.
      CLINICAL IMPLICATIONS: A lower-dose ICS with a LABA is effective in controlling
      inflammation and providing clinical asthma control, confirming current guideline
      recommendations.

PMID- 16815138
TI  - Prevention of asthma during the first 5 years of life: a randomized controlled
      trial.
AB  - BACKGROUND: Early life exposures may be important in the development of asthma
      and allergic disease. OBJECTIVE: To test house dust mite (HDM) avoidance and
      dietary fatty acid modification, implemented throughout the first 5 years of
      life, as interventions to prevent asthma and allergic disease. METHODS: We
      recruited newborns with a family history of asthma antenatally and randomized
      them, separately, to HDM avoidance or control and to dietary modification or
      control. At age 5 years, they were assessed for asthma and eczema and had skin
      prick tests for atopy. RESULTS: Of 616 children randomized, 516 (84%) were
      evaluated at age 5 years. The HDM avoidance intervention resulted in a 61%
      reduction in HDM allergen concentrations (microg/g dust) in the child's bed but
      no difference in the prevalence of asthma, wheeze, or atopy (P > .1). The
      prevalence of eczema was higher in the active HDM avoidance group (26% vs 19%; P
      = .06). The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the
      active diet group (5.8 vs 7.4; P < .0001). However, the prevalence of asthma,
      wheezing, eczema, or atopy did not differ between the diet groups (P > .1).
      CONCLUSION: Further research is required to establish whether other interventions
      can be recommended for the prevention of asthma and allergic disease. CLINICAL
      IMPLICATIONS: House dust mite avoidance measures and dietary fatty acid
      modification, as implemented in this trial during infancy and early childhood,
      did not prevent the onset of asthma, eczema, or atopy in high-risk children.

PMID- 16815139
TI  - Epicutaneous aeroallergen exposure induces systemic TH2 immunity that predisposes
      to allergic nasal responses.
AB  - BACKGROUND: Atopic individuals are predisposed to mounting vigorous T(H)2-type
      immune responses to environmental allergens. The skin is often the first organ
      that manifests allergic disease and may provide an early entry point for antigen
      sensitization. OBJECTIVE: We sought to determine whether epicutaneous exposure to
      the aeroallergen Aspergillus fumigatus induces nasal allergic responses.
      Furthermore, we aimed to examine the mechanism involved. METHODS: Wild-type and
      signal transducer and activator of transcription 6 (STAT6)-deficient mice were
      exposed to epicutaneous A fumigatus and control antigen ovalbumin. Nasal
      inflammation and responsiveness to methacholine were monitored. RESULTS: Exposure
      to epicutaneous A fumigatus antigen induced a marked atopic dermatitis-like
      phenotype in a manner significantly more efficient than epicutaneous ovalbumin. A
      single A fumigatus intranasal challenge induced clinical nasal responses and
      hyperresponsiveness to methacholine in the nose as manifested by nasal symptoms,
      accompanied by allergic airway and nasal inflammation. Mechanistic analysis using
      gene-targeted mice revealed that the clinical nasal responses and
      hyperresponsiveness were STAT6-dependent. Although STAT6 was required for changes
      in nasal responses, it was not required for epicutaneous pathology except
      eosinophilia. CONCLUSION: Epicutaneous exposure to the aeroallergen A fumigatus
      potently primes for STAT6-dependent nasal responses. These results draw attention
      to the cooperative interaction between the nasal tract and skin. CLINICAL
      IMPLICATIONS: The skin is a potent site for antigen sensitization in the
      development of experimental allergic rhinitis.

PMID- 16815141
TI  - Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone
      propionate.
AB  - BACKGROUND: Inhaled corticosteroids are highly effective in asthma, reducing
      inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes
      are major mediators of airway obstruction and display proinflammatory effects.
      Although the synthesis of leukotrienes is not affected by corticosteroid
      treatment, the influence of corticosteroids on the leukotriene pathway remains
      unresolved. OBJECTIVE: We investigated whether or not bronchial responsiveness to
      leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with
      asthma. METHODS: In 13 subjects with mild asthma, inhalation challenges with
      methacholine and LTD(4) were performed on consecutive days before and after 2
      weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double
      blind, randomized, placebo-controlled study with crossover design and 3 weeks of
      washout between periods. Exhaled nitric oxide was measured as a marker of
      corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an
      index of cysteinyl-leukotriene biosynthesis. RESULTS: Fluticasone produced a
      significant decrease in methacholine responsiveness, corresponding to 2.6-fold
      shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled
      nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same
      subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations.
      CONCLUSION: These new data indicate that neither the biosynthesis nor the actions
      of leukotrienes appear to be sensitive to inhaled corticosteroids. CLINICAL
      IMPLICATIONS: The study provides mechanistic support for the additive therapeutic
      efficacy of antileukotrienes and inhaled corticosteroids in asthma.

PMID- 16815140
TI  - Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated
      with asthma and associated phenotypes.
AB  - BACKGROUND: The gene encoding acyloxyacyl hydroxylase (AOAH), an enzyme that
      hydrolyzes secondary fatty acyl chains of LPS, is localized on chromosome 7p14
      p12, where evidence for linkage to total IgE (tIgE) concentrations and asthma has
      been previously reported. OBJECTIVE: We hypothesized that variants in AOAH are
      associated with asthma and related phenotypes. Because both AOAH and soluble CD14
      respond to LPS, we tested for gene-gene interaction. METHODS: We investigated the
      association between 28 single nucleotide polymorphisms throughout the AOAH gene
      and asthma, concentrations of tIgE, the ratio of IL-13/IFN-gamma, and soluble
      CD14 levels among 125 African Caribbean, multiplex asthmatic pedigrees (n = 834).
      Real-time PCR was used to assess whether AOAH cDNA expression differed with AOAH
      genotype. RESULTS: Significant effects were observed for all 4 phenotypes and
      AOAH markers in 3 distinct regions (promoter, introns 1-6, and the intron 12/exon
      13 boundary/intron 13 region) by means of single-marker and haplotype analyses,
      with the strongest evidence for a 2-single-nucleotide-polymorphism haplotype and
      log[tIgE] (P = .006). There was no difference in AOAH expression levels by AOAH
      genotype for any of the markers. Comparing genotypic distributions at both the
      AOAH marker rs2727831 and CD14(-260)C >T raises the possibility of gene-gene
      interaction (P = .006-.036). CONCLUSION: Our results indicate that polymorphisms
      in markers within the AOAH gene are associated with risk of asthma and associated
      quantitative traits (IgE and cytokine levels) among asthmatic subjects and their
      families in Barbados, and there is an interactive effect on tIgE and asthma
      concentrations between an AOAH marker and the functional CD14(-260)C >T
      polymorphism. CLINICAL IMPLICATIONS: AOAH is a novel innate immunity candidate
      gene associated with asthma and related phenotypes in an African ancestry
      population.

PMID- 16815142
TI  - Airway cytokine expression measured by means of protein array in exhaled breath
      condensate: correlation with physiologic properties in asthmatic patients.
AB  - BACKGROUND: Simultaneous monitoring of airway inflammation and physiology might
      be useful for asthma management. OBJECTIVE: We examined the upregulated molecules
      in asthmatic airways. Furthermore, we investigated the relationship between these
      molecules and the airway physiologic properties of asthma. METHODS: Ten
      nonsmoking healthy subjects and 16 steroid-naive asthmatic patients were
      enrolled. Exhaled breath condensate (EBC) sampling, spirometry, and methacholine
      inhalation challenge were performed on one occasion in this cross-sectional
      study. Peak expiratory flow was also measured for 4 weeks. Airway cytokine
      chemokine-growth factor production was analyzed with a protein array. RESULTS:
      The expressions of IL-4, IL-8, IL-17, TNF-alpha, RANTES, IFN-gamma-inducible
      protein 10, TGF-beta, and macrophage inflammatory protein 1alpha and 1beta were
      significantly upregulated in asthmatic airways compared with those of nonsmoking
      healthy subjects. Among the upregulated molecules, RANTES expression was
      significantly correlated with the parameters that represent airway caliber,
      FEV(1) and respiratory resistance values. In addition, the levels of both TNF
      alpha and TGF-beta were significantly correlated with the methacholine threshold
      and peak expiratory flow variability for the week. CONCLUSION: Inflammatory
      molecule analysis with EBC appeared to be useful for monitoring the asthmatic
      airway condition. CLINICAL IMPLICATIONS: Measurements of cytokine levels in EBC
      might be a promising approach to assess the efficacy of pharmacologic
      interventions and to investigate the pathophysiology of asthma.

PMID- 16815143
TI  - The course of allergen-induced leukocyte infiltration in human and experimental
      asthma.
AB  - BACKGROUND: Although the timing of allergen-induced bronchoconstriction is well
      defined, there is little information about the kinetics of allergen-induced
      leukocyte infiltration in asthma and its comparability between human and animal
      models of asthma. OBJECTIVE: To investigate systematically allergen-induced
      leukocyte infiltration into the airway lumen in human and experimental asthma by
      using bronchoalveolar lavage. METHODS: Patients with allergic asthma were lavaged
      at different time points as long as 1 week after segmental allergen challenge.
      Allergen-sensitized mice were lavaged as long as 3 weeks after allergen
      challenge. Differential cell counts, lymphocyte subsets, and cytokines were
      assessed in bronchoalveolar lavage fluid. RESULTS: In both models, neutrophil
      infiltration was a relatively early event (maximum: 18 hours after challenge). In
      contrast, eosinophil infiltration peaked 42 hours (human model) to 4 days (mouse
      model) after allergen challenge, paralleled by an IL-5 peak in this period. There
      were elevated macrophage counts over a period of several days after allergen
      challenge in both models. Lymphocytes (predominantly CD4+ T cells) peaked 18
      hours after challenge in the human model, but not until 2 weeks after challenge
      in the murine model. CONCLUSION: Early neutrophil accumulation (within hours
      after challenge) and delayed eosinophil accumulation (within days after
      challenge) in the airway lumen are common features of allergen-induced airway
      inflammation, whereas lymphocyte kinetics are dependent on the asthma model.
      CLINICAL IMPLICATIONS: Similarities in the infiltration kinetics of granulocytes
      after allergen challenge suggest a common role for these cells in asthma, whereas
      the presumed orchestration of allergic inflammation by lymphocytes appears to
      differ between the models.

PMID- 16815144
TI  - Periostin: a novel component of subepithelial fibrosis of bronchial asthma
      downstream of IL-4 and IL-13 signals.
AB  - BACKGROUND: Subepithelial fibrosis is a cardinal feature of bronchial asthma.
      Collagen I, III, and V; fibronectin; and tenascin-C are deposited in the lamina
      reticularis. Extensive evidence supports the pivotal role of IL-4 and IL-13 in
      subepithelial fibrosis; however, the precise mechanism remains unclear. We have
      previously identified the POSTN gene encoding periostin as an IL-4/IL-13
      inducible gene in bronchial epithelial cells. Periostin is thought to be an
      adhesion molecule because it possesses 4 fasciclin I domains. OBJECTIVE: We
      explore the possibility that periostin is involved in subepithelial fibrosis in
      bronchial asthma. METHODS: We analyzed induction of periostin in lung fibroblasts
      by IL-4 or IL-13. We next analyzed expression of periostin in patients with
      asthma and in ovalbumin-sensitized and ovalbumin-inhaled mice. Furthermore, we
      examined the binding ability of periostin to other extracellular matrix proteins.
      RESULTS: Both IL-4 and IL-13 induced secretion of periostin in lung fibroblasts
      independently of TGF-beta. Periostin colocalized with other extracellular matrix
      proteins involved in subepithelial fibrosis in both asthma patients and ovalbumin
      sensitized and ovalbumin-inhaled wild-type mice, but not in either IL-4 or IL-13
      knockout mice. Periostin had an ability to bind to fibronectin, tenascin-C,
      collagen V, and periostin itself. CONCLUSION: Periostin secreted by lung
      fibroblasts in response to IL-4 and/or IL-13 is a novel component of
      subepithelial fibrosis in bronchial asthma. Periostin may contribute to this
      process by binding to other extracellular matrix proteins. CLINICAL IMPLICATIONS:
      Periostin induced by IL-4/IL-13 shows promise in inhibiting subepithelial
      fibrosis in bronchial asthma.

PMID- 16815145
TI  - Serine protease inhibitors nafamostat mesilate and gabexate mesilate attenuate
      allergen-induced airway inflammation and eosinophilia in a murine model of
      asthma.
AB  - BACKGROUND: Serine proteases such as mast cell tryptase and certain allergens are
      important in the pathogenesis of allergic inflammation of asthma. OBJECTIVE: We
      sought to investigate the effects of serine protease inhibitors nafamostat
      mesilate (FUT), gabexate mesilate (FOY), and ulinastatin (UTI) on airway
      inflammation in a mouse model of allergic asthma. METHODS: BALB/c mice were
      sensitized to Dermatophagoides pteronyssinus (Der p) and intratracheally
      challenged with Der p (0.5 mg/mL). Therapeutic doses of FUT (0.0625 mg/kg), FOY
      (20 mg/kg), and UTI (10,000 U/kg) were intra-peritoneally injected into 3
      corresponding sensitized mice during the sensitization phase (protocol 1) or 24
      hours after allergen challenge (protocol 2). RESULTS: Both FUT-treated and FOY
      treated sensitized mice had reduced mast cells activation, airway
      hyperresponsiveness, attenuated eosinophils infiltrations, and decreased Der p
      induced IL-4 and TNF-alpha, but increased IL-12 cytokine production in
      bronchoalveolar lavage fluid compared with nontreated mice. Furthermore, FUT
      treatment downregulated the expression of IL-1beta, TNF-alpha, IL-6, eotaxin,
      inducible NO synthase, CD86, and nuclear factor-kappaB activation, but enhanced
      the expression of IL-12 and IL-10 in Der p-stimulated alveolar macrophages. UTI
      treated mice have no significant change of the aforementioned measurements
      compared with nontreated sensitized mice. CONCLUSION: Nafamostat mesilate and FOY
      exerting the therapeutic effect in allergen-induced airway inflammation was a
      result not only of their inhibitory action in the early phase of mast cells
      activation but also of immunoregulatory function in the late phase of allergic
      inflammation. Such properties of FUT and FOY might be a potential therapeutic
      approach for asthma. CLINICAL IMPLICATIONS: The clinical used of serine protease
      inhibitors FUT and FOY may also have implications for treating airway
      inflammation of asthma.

PMID- 16815146
TI  - Montelukast regulates eosinophil protease activity through a leukotriene
      independent mechanism.
AB  - BACKGROUND: Migration of eosinophils into bronchial mucosa requires proteolysis.
      Montelukast, a cysteinyl leukotriene (CysLT) 1 receptor antagonist used in asthma
      treatment, decreases eosinophil infiltration into the asthmatic airways,
      suggesting that CysLTs modulate eosinophil protease activity. OBJECTIVE: We
      sought to determine whether CysLTs and montelukast regulate eosinophil protease
      activity. METHODS: Purified blood eosinophils were treated with or without
      montelukast; MK-0591, a 5-lipoxygenase-activating protein inhibitor; or
      leukotriene (LT) D(4). Migration assays through Matrigel were performed in the
      presence of 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent
      eosinophil chemotactic factor, or LTD(4). Expression of molecules implicated in
      plasmin generation and matrix metalloproteinase (MMP) 9 release were also
      evaluated. RESULTS: Montelukast and MK-0591 decreased eosinophil migration
      promoted by 5-oxo-ETE, whereas LTD(4) failed to induce eosinophil migration.
      However, LTD(4) significantly boosted the migration rate obtained with a
      suboptimal concentration of 5-oxo-ETE and partially reversed the inhibition
      obtained with MK-0591. Montelukast significantly reduced the maximal rate of
      activation of plasminogen into plasmin by eosinophils obtained with 5-oxo-ETE. 5
      Oxo-ETE increased the number of eosinophils expressing urokinase plasminogen
      activator receptor and stimulated secretion of MMP-9. Montelukast, but neither MK
      0591 nor LTD(4), reduced the expression of urokinase plasminogen activator
      receptor and the secretion of MMP-9 and increased total cellular activity of
      urokinase plasminogen activator and the expression of plasminogen activator
      inhibitor 2 mRNA. CONCLUSION: Montelukast inhibits eosinophil protease activity
      in vitro through a mechanism that might be independent of its antagonist effect
      on CysLT 1 receptor. CLINICAL IMPLICATIONS: This could partially explain
      montelukast's anti-inflammatory effect in asthma and eventually amplify to
      improve its therapeutic efficacy.

PMID- 16815147
TI  - Peroxisome proliferator activated receptor-gamma modulates reactive oxygen
      species generation and activation of nuclear factor-kappaB and hypoxia-inducible
      factor 1alpha in allergic airway disease of mice.
AB  - BACKGROUND: Reactive oxygen species (ROSs) play a crucial role in the
      pathogenesis of airway inflammation. Peroxisome proliferator activated receptor
      (PPAR)-gamma is also involved in airway inflammation. We have demonstrated that
      the administration of PPARgamma agonists or adenovirus carrying PPARgamma cDNA
      (AdPPARgamma) reduced bronchial inflammation and airway hyperresponsiveness.
      However, the effects of PPARgamma on ROS generation in conditions associated with
      airway inflammation have not been clarified. OBJECTIVE: This study aimed to
      investigate the effects of the PPARgamma on ROS generation in allergic airway
      disease of mice. METHODS: We have used a female C57BL/6 mouse model for allergic
      airway disease to determine the role of PPARgamma. RESULTS: In this study with an
      ovalbumin-induced murine model of allergic airway disease, the increased ROS
      generation and the increased expression of T(H)2 cell cytokines, adhesion
      molecules, chemokines, and vascular endothelial growth factor in lungs after
      ovalbumin inhalation were significantly reduced by the administration of
      PPARgamma agonists or AdPPARgamma. We also showed that the increased nuclear
      factor-kappaB and hypoxia-inducible factor 1alpha levels in nuclear protein
      extracts of lung tissues after ovalbumin inhalation were decreased by the
      administration of PPARgamma agonists or AdPPARgamma. CONCLUSION: These results
      indicate that the effects of PPARgamma are mediated by the modulation of ROS
      generation and activation of redox-sensitive transcription factor nuclear factor
      kappaB and HIF-1alpha in allergic airway disease of mice. CLINICAL IMPLICATIONS:
      Thus, these findings provide a pivotal molecular mechanism for the use of
      PPARgamma agonists to prevent and/or treat asthma and other airway inflammatory
      disorders.

PMID- 16815148
TI  - Short course of systemic corticosteroids in sinonasal polyposis: a double-blind,
      randomized, placebo-controlled trial with evaluation of outcome measures.
AB  - BACKGROUND: Topical and systemic corticosteroids are the first choice in medical
      treatments for sinonasal polyposis, but surprisingly, there is no high-level
      evidence for the efficacy of oral corticosteroids. OBJECTIVE: The aim of this
      study was to establish the efficacy of a short course of oral prednisolone in
      ameliorating the symptoms of sinonasal polyposis, as well as reducing mucosal
      inflammation assessed by means of nasendoscopy and magnetic resonance imaging
      (MRI). A secondary aim was to evaluate the relationship between outcome measures.
      METHODS: Subjects with symptomatic endoscopically diagnosed sinonasal polyposis
      received 50 mg of prednisolone daily for 14 days or placebo. Outcome was
      quantified by using the modified 31-item Rhinosinusitis Outcome Measure
      questionnaire, physician's assessment, nasendoscopy with photography, and MRI.
      RESULTS: There were 20 subjects in each treatment group. Only the prednisolone
      treated group showed significant improvement in nasal symptoms (P < .001). The
      Rhinosinusitis Outcome Measure score improved in both groups, but the
      prednisolone-treated group had significantly greater improvement than the placebo
      group (P < .001). Objectively, there was significant reduction in polyp size, as
      noted with nasendoscopy (P < .001) and MRI (P < .001), only in the prednisolone
      treated group. The outcome measures correlated with each other; the highest level
      of correlation was between the objective measures of nasendoscopy and MRI (R(2) =
      0.76, P < .001). There were no significant adverse events. CONCLUSION: This trial
      clearly establishes clinically significant improvement in the symptoms and
      pathology of sinonasal polyposis with a short course of systemic corticosteroids.
      MRI scanning and quantitative nasendoscopic photography are objective and valid
      tools for assessing the outcome of treatment in this condition. CLINICAL
      IMPLICATIONS: A 14-day course of 50 mg of prednisolone is safe and effective
      therapy for symptomatic nasal polyposis.

PMID- 16815149
TI  - Analysis of gene expression profiles of normal human nasal mucosa and nasal polyp
      tissues by SAGE.
AB  - BACKGROUND: A systemic determination of gene expression profiles in nasal polyp
      compared with normal nasal mucosa would contribute considerably to the
      investigation of the disease marker in various rhinopathy and general knowledge
      on the formation of human nasal polyp. OBJECTIVE: The aim of this study was to
      identify the transcriptome of the normal human nasal mucosa and nasal polyp by
      the serial analysis of gene expression. METHODS: mRNA was extracted from normal
      inferior turbinate mucosa and nasal polyp. Short sequences (tags), each one
      usually corresponding to a distinct transcript, was isolated and concatemerized
      into long DNA molecules, which were cloned and sequenced. RESULTS: We detected
      65,305 tags for normal nasal mucosa and 55,829 tags for nasal polyp, representing
      20,629 and 17,636 potential transcripts species, respectively. Of the unique tags
      encountered more than once, 92% (normal nasal mucosa) and 90% (nasal polyp)
      matched known genes or expressed sequence tags, whereas the remainder did not
      match any GenBank sequences. Therefore, 504 and 539 novel transcripts were
      identified in normal nasal mucosa and nasal polyp, respectively. Although the
      expression levels of most transcripts in both libraries were similar, 114
      transcripts were differentially expressed at a statistically significant level (P
      < .05)-that is, 65 and 49 transcripts among them were expressed at a higher level
      in normal nasal mucosa and nasal polyp, respectively. CONCLUSION: This
      information should be very useful for basic knowledge as well as for future
      studies on pathophysiological conditions of human nasal mucosa, providing some
      clues to evaluate the altered factors in a variety of rhinopathies. CLINICAL
      IMPLICATIONS: The results of this study might contribute to general knowledge on
      the formation of human nasal polyp.

PMID- 16815150
TI  - Neonatal exposure with LPS and/or allergen prevents experimental allergic airways
      disease: development of tolerance using environmental antigens.
AB  - BACKGROUND: Studies show that children in rural environments develop less asthma
      and allergic rhinitis than their urban counterparts. This may be a result, in
      part, of neonatal exposure to environmental antigens such as LPS and/or early
      exposure to allergens. OBJECTIVE: This study examined the effects of neonatal
      allergen and/or LPS exposure on subsequent immune responses to allergen. METHODS:
      Newborn mice were exposed to LPS and/or ovalbumin. At age 6 weeks, these animals
      were sensitized and challenged with ovalbumin, and airway inflammation,
      hyperresponsiveness, and cytokine expression were assessed. RESULTS: Animals
      exposed to LPS in the neonatal period developed T cells expressing CD25 and IL-10
      on sensitization and challenge. They demonstrated abrogation of airway
      hyperresponsiveness and significant decreases in IL-13 from bronchoalveolar
      lavage fluid and in specific IgE. IL-4-expressing spleen cells were also
      significantly decreased. Mice exposed in the neonatal period to ovalbumin
      demonstrated airway hyporesponsiveness after subsequent ovalbumin sensitization
      and challenge and did not produce specific IgE. In contrast, these animals showed
      increases in IFN-gamma. Animals exposed to both LPS and ovalbumin developed a
      response characterized by IL-10 and IFN-gamma-expressing T cells. CONCLUSION:
      This suggests that mucosal antigen exposure in the neonatal period results in
      inhibition of allergic responses to environmental allergens. Early LPS exposure
      directs mucosal responses toward tolerance, whereas ovalbumin exposure follows
      the T(H)1-type response on subsequent sensitization. CLINICAL IMPLICATIONS: This
      study suggests that prevention of airways allergy may be best achieved by
      appropriate exposure of the airway mucosa early in life to environmental
      antigens.

PMID- 16815151
TI  - Diagnosis and treatment of atopic dermatitis in children and adults: European
      Academy of Allergology and Clinical Immunology/American Academy of Allergy,
      Asthma and Immunology/PRACTALL Consensus Report.
AB  - There are remarkable differences in the diagnostic and therapeutic management of
      atopic dermatitis practiced by dermatologists and pediatricians in different
      countries. Therefore, the European Academy of Allergy and Clinical Immunology and
      the American Academy of Allergy, Asthma and Immunology nominated expert teams who
      were given the task of finding a consensus to serve as a guideline for clinical
      practice in Europe as well as in North America. The consensus report is part of
      the PRACTALL initiative, which is endorsed by both academies.

PMID- 16815152
TI  - Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to
      foods, drugs, and insects.
AB  - This review highlights some of the research advances in anaphylaxis;
      hypersensitivity reactions to foods, drugs, and insects; and allergic skin
      disease that were reported primarily in the Journal in 2005. Although studies
      documented deficiencies in community management of anaphylaxis, guidelines and
      National Institutes of Health summary reports provide direction toward improved
      research and education. At least 9% of young children "outgrow" a tree nut
      allergy. Advances in food allergy diagnosis include reports of probability of
      reactions to peanut at various peanut-specific IgE concentrations and skin test
      response size and the utility of evaluating IgE binding to specific epitopes.
      Future food allergy treatments might include selection of "less allergenic" fruit
      cultivars, genetic silencing of major allergens, and treatment of allergic
      patients with Chinese herbal remedies. Osteopontin might be a useful biomarker
      for success of venom immunotherapy. Progress in our understanding of the
      immunology of atopic dermatitis and autoimmune urticaria has also been made.
      These observations will likely contribute toward optimizing management of these
      common allergic disorders.

PMID- 16815153
TI  - Cytokines and chemokines orchestrate atopic skin inflammation.
AB  - Atopic dermatitis (AD) is a common pruritic and chronically relapsing
      inflammatory skin disease. The pathophysiology of AD includes disturbed skin
      barrier functions, frequent allergic responses against allergens, defects in the
      antimicrobial immune defense, and a genetic predisposition. In this review we
      summarize advances in our understanding of the complex interdependent network of
      members of the rapidly growing protein superfamilies of cytokines and chemokines
      that lead to the development of AD.

PMID- 16815154
TI  - Role of vasculature in atopic dermatitis.
AB  - Atopic dermatitis (AD) lesions are characterized by differences in the activation
      state of endothelial cells and vascular smooth muscle cells and the release of
      inflammatory mediators by and toward the vasculature. The vascular system,
      including endothelial cells and smooth muscle cells, is ultimately involved in
      clinical symptoms of AD, such as erythema, edema, leukocyte recruitment, and
      white dermographism. Various mediators and bidirectional neurovascular
      interactions regulate the inflammatory response during AD. T cell-endothelial
      cell interactions are a crucial component to establish acute AD. Various immune
      cells, including monocytes and mast cells, communicate with the endothelium by
      releasing inflammatory mediators, thereby stimulating inflammatory mediator
      release from activated endothelial cells. The process of adhesion, tethering, and
      transmigration of infiltrating cells is a highly regulated and an active
      communication process between endothelial cells and leukocytes. Endothelial cells
      play a pivotal role in the pathophysiology of AD and represent future targets for
      the treatment of AD.

PMID- 16815155
TI  - Management of sleep disturbance associated with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common childhood skin disease that also affects
      adults. Sleep problems are frequently associated with AD and negatively affect
      both patients and their families. Although this problem is well recognized, there
      are currently limited studies of patients with AD to guide clinical management of
      sleep disturbances. This targeted review will inform clinicians of the potential
      therapeutic agents available to manage sleep disturbances and will review
      literature relevant to improving the sleep of children and adults with AD. On the
      basis of our clinical experience and the limited data available, we provide a
      suggested algorithm for clinicians treating sleep problems associated with AD,
      but clearly more studies are needed to both further characterize the sleep of
      patients with AD and to test the efficacy and effectiveness of candidate agents
      in clinical trials.

PMID- 16815156
TI  - Innate immune defects in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common, chronic inflammatory skin disease that
      becomes clinically apparent in the pediatric population. It is well recognized
      that subjects with AD have an increased susceptibility to cutaneous colonization
      and infection with bacteria, fungi, and viruses. The notion that subjects with AD
      have a cutaneous immune defect has received widespread acceptance, and several
      plausible explanations for this have been proposed. We will review the evidence
      that this susceptibility to cutaneous infection is at least in part due to a
      defect in the first line of defense against microbes, namely the innate immune
      system.

PMID- 16815157
TI  - How epidemiology has challenged 3 prevailing concepts about atopic dermatitis.
AB  - We challenge 3 prevailing concepts in understanding atopic dermatitis using data
      from epidemiologic studies. First, we show that although atopy is associated with
      atopic dermatitis to some degree, its importance is not likely to be a simple
      cause-and-effect relationship, especially at a population level. Our
      epidemiologic data do not exclude a contributory role for IgE-mediated
      immunologic processes, especially in those with existing and severe disease.
      Second, evidence is presented that does not support a straightforward inverse
      relationship between infections and atopic dermatitis risk. A link, if present,
      is likely to be more complex, depending critically on the timing and type of
      infectious exposure. Third, recent evidence suggests that the risk of subsequent
      childhood asthma is not increased in children with early atopic dermatitis who
      are not also early wheezers, suggesting a co-manifestation of phenotypes rather
      than a progressive atopic march. Collectively, these observations underline the
      importance of epidemiologic studies conducted at a population level to gain a
      more balanced understanding of the enigma of atopic dermatitis.

PMID- 16815158
TI  - Loss-of-function variations within the filaggrin gene predispose for atopic
      dermatitis with allergic sensitizations.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a
      strong genetic background. One of the characteristic features of AD and causative
      factor for the disease is an impaired epidermal skin barrier based on a primary
      defect of epidermal differentiation. OBJECTIVES: Recently, 2 loss-of-function
      mutations (R501X and 2282derl4) in the filaggrin gene (FLG) that cause ichthyosis
      vulgaris, one of the most common inherited skin disorders of keratinization, have
      been reported to be strong predisposing factors for AD. METHODS: We evaluated the
      association of the loss-of-function mutations R501X and 2282del4 within the FLG
      gene in a large collection of 476 well-characterized white German families with
      AD by using the transmission-disequilibrium test. RESULTS: Our family-based
      approach revealed prominent associations between the 2 loss-of-function FLG
      mutations and AD, as previously observed in a traditional Mendelian linkage
      analysis and case-control cohort analysis approach. In addition, we observed
      associations of the FLG mutations in particular with the extrinsic subtype of AD,
      which is characterized by high total serum IgE levels and concomitant allergic
      sensitizations. Furthermore, FLG mutations are significantly associated with
      palmar hyperlinearity in patients with AD, which represents a shared feature of
      AD and ichthyosis vulgaris. CONCLUSION: Together these data implicate that FLG is
      the first really strong genetic factor identified in a common complex disease.
      CLINICAL IMPLICATIONS: These findings underline the crucial role of the skin
      barrier in preventing allergic sensitization.

PMID- 16815159
TI  - A network-based analysis of the late-phase reaction of the skin.
AB  - BACKGROUND: The late-phase reaction (LPR) of the skin is an in vivo model of
      allergic inflammation. OBJECTIVE: We sought to identify disease-associated
      pathways in the LPR using a network-based analysis. METHODS: The LPR was examined
      by means of DNA microarray analysis of skin biopsy specimens from 10 patients
      with allergic rhinitis and 10 healthy control subjects. The results were further
      analyzed in 2 different materials consisting of nasal fluids and allergen
      challenged CD4(+) T cells from patients with allergic rhinitis. RESULTS: The DNA
      microarray analysis revealed several genes of known relevance to allergy. The
      eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot
      Leyden crystal protein differed most in expression. A network-based analysis
      showed upregulation of IL-4- and CCL4-dependent pathways and downregulation of a
      TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells and chemotactic for
      eosinophils. We hypothesized that allergen induces release of CCL4 from T(H)2
      cells and that this contributes to influx of eosinophils. Further analysis showed
      increase of CCL4 protein in nasal fluids from allergic patients during the
      season. Allergen challenge of PBMCs resulted in proliferation of T(H)2 cells and
      increased production of CCL4 in CD4(+) T cells from allergic patients. An
      analysis of the DNA microarray data revealed a significant correlation between
      CCL4 and the eosinophil marker CLC. CONCLUSION: A network-based analysis of the
      LPR showed increased activity of IL-4- and CCL4- dependent pathways and
      downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4
      from T(H)2 cells might contribute to influx of eosinophils during the LPR.
      CLINICAL IMPLICATIONS: Involvement of multiple interacting pathways indicates
      that it might be difficult to identify one single mediator as a biomarker or drug
      target in allergic inflammation.

PMID- 16815160
TI  - Patient perspectives on the management of atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is increasingly common, with a point
      prevalence of more than 30% in some countries, and is characterized by visible
      skin lesions and intense itching. OBJECTIVE: The International Study of Life with
      Atopic Eczema (ISOLATE) is the first large-scale study to assess the effect of AD
      on the lives of patients and society, how patients and caregivers manage the
      condition, and how well patients and caregivers currently believe that AD is
      controlled. METHODS: Two thousand two patients (>13 years) and caregivers of
      children (2-13 years) with moderate-to-severe AD randomly selected from 8
      countries underwent standardized telephone interviews using questions developed
      in collaboration with national eczema patient groups and physicians. RESULTS:
      During each year, patients spend, on average, 1 of 3 days in flare. The majority
      of patients receive prescription topical corticosteroids to treat flares;
      however, 49% of respondents are concerned about using these agents. On average,
      patients and caregivers delay initiating treatment for 7 days after onset of a
      flare. Only 24% of patients and caregivers feel confident they can manage AD
      flares adequately. Seventy-five percent of caregivers and patients feel that
      being able to effectively control AD would be the single most important
      improvement to their or their child's quality of life. The avoidable secondary
      economic cost of AD is estimated at 2 billion Euro per year across the European
      Union. CONCLUSION: ISOLATE highlights the need to improve patients' control of AD
      to reduce the significant effect this condition has on the patient and society.
      CLINICAL IMPLICATIONS: ISOLATE shows that patients with AD are untreated for half
      the time they are in flare, and thus there is an urgent need for physicians to
      ensure that the patients are educated and confident in using medication as
      prescribed to gain disease control.

PMID- 16815161
TI  - Activation of T cells by carbamazepine and carbamazepine metabolites.
AB  - BACKGROUND: T-cell-mediated hypersensitivity is a rare but serious manifestation
      of drug therapy. OBJECTIVES: To explore the mechanisms of drug presentation to T
      cells and the possibility that generation of metabolite-specific T cells may
      provoke cross-sensitization between drugs. METHODS: A lymphocyte transformation
      test was performed on 13 hypersensitive patients with carbamazepine,
      oxcarbazepine, and carbamazepine metabolites. Serial dilution experiments were
      performed to generate drug (metabolite)-specific T-cell clones to explore the
      structural basis of the T-cell response and mechanisms of antigen presentation. 3
      Dimensional energy-minimized structures were generated by using computer
      modeling. The role of drug metabolism was analyzed with 1-aminobenzotriazole.
      RESULTS: Lymphocytes and T-cell clones proliferated with carbamazepine,
      oxcarbazepine, and some (carbamazepine 10,11 epoxide, 10-hydroxy carbamazepine)
      but not all stable carbamazepine metabolites. Structure activity studies using 29
      carbamazepine (metabolite)-specific T-cell clones revealed 4 patterns of drug
      recognition, which could be explained by generation of preferred 3-dimensional
      structural conformations. T cells were stimulated by carbamazepine (metabolites)
      bound directly to MHC in the absence of processing. The activation threshold for
      T-cell proliferation varied between 5 minutes and 4 hours. 1-Aminobenzotriazole,
      which inhibits cytochrome P450 activity, did not prevent carbamazepine-related T
      cell proliferation. Substitution of the terminal amine residue of carbamazepine
      with a methyl group diminished T-cell proliferation. CONCLUSION: These data show
      that carbamazepine and certain stable carbamazepine metabolites stimulate T cells
      rapidly via a direct interaction with MHC and specific T-cell receptors. CLINICAL
      IMPLICATIONS: Some patients with a history of carbamazepine hypersensitivity
      possess T cells that cross-react with oxcarbazepine, providing a rationale for
      cross-sensitivity between the 2 drugs.

PMID- 16815162
TI  - Cooking birch pollen-related food: divergent consequences for IgE- and T cell
      mediated reactivity in vitro and in vivo.
AB  - BACKGROUND: The major birch pollen allergen Bet v 1 cross-reacts with homologous
      food allergens, resulting in IgE-mediated oral allergy syndromes (OASs). To avoid
      this food, allergy allergologists and guidebooks advise patients to consume birch
      pollen-related foods after heating. OBJECTIVE: We sought to evaluate whether
      cooked Bet v 1-related food allergens induce IgE- and T cell-mediated reactions
      in vitro and in vivo. METHODS: Recombinant Bet v 1, Mal d 1 (apple), Api g 1
      (celery), and Dau c 1 (carrot) were incubated at increasing temperatures. Protein
      structures were determined by means of circular dichroism. Mediator release was
      tested in basophil activation assays. PBMCs and Bet v 1-specific T-cell lines
      with known epitope specificity were stimulated with native and cooked food
      allergens. Patients with birch pollen allergy who experienced OAS and the
      exacerbation of atopic dermatitis (AD) on ingestion of fresh apple, celery, or
      carrot were retested in double-blind, placebo-controlled food challenges with the
      respective foods in cooked form. RESULTS: In vitro, cooked food allergens lost
      the capacity to bind IgE and to induce mediator release but had the same potency
      to activate Bet v 1-specific T cells as native proteins. In vivo, ingestion of
      cooked birch pollen-related foods did not induce OAS but caused atopic eczema to
      worsen. CONCLUSION: T-cell cross-reactivity between Bet v 1 and related food
      allergens occurs independently of IgE cross-reactivity in vitro and in vivo. In
      patients with AD, the resulting immune reaction can even manifest as late
      eczematous skin reactions. Therefore the view that cooked pollen-related foods
      can be consumed without allergologic consequences should be reconsidered.
      CLINICAL IMPLICATIONS: Symptom-free consumed pollen-related food allergens might
      cause T cell-mediated late-phase skin reactions in patients with pollen allergy
      and AD.

PMID- 16815163
TI  - Predictive value of skin prick tests using recombinant allergens for diagnosis of
      peanut allergy.
AB  - BACKGROUND: Current diagnosis of peanut allergy relies on natural extracts that
      lack standardization. Recombinant DNA technology allows production of pure
      biochemically characterized proteins. Their usefulness for peanut allergy
      diagnosis is not established. OBJECTIVE: This study aimed to evaluate the
      diagnostic value of the 3 major recombinant peanut allergens. METHODS:
      Recombinant (r) Ara h 1, rAra h 2, and rAra h 3 were produced according to the
      recommendations of good manufacturing practice for recombinant allergens. Skin
      prick tests (SPTs) and IgE ELISA assays were performed in 30 patients with peanut
      allergy and 30 control subjects without food allergy: 15 nonatopic and 15
      sensitized to birch pollen. Disease severity was graded by clinical scoring.
      RESULTS: All patients with peanut allergy showed positive SPT results to rAra h
      2; 40% reacted with rAra h 1 and 27% with rAra h 3. No control subjects reacted
      with any of the recombinant allergens. Monosensitization to rAra h 2 was observed
      in 53% of patients. Neither SPT size nor levels of specific IgE were correlated
      with the disease severity. However, patients with monosensitization to rAra h 2
      had a significantly lower severity score than polysensitized subjects and a lower
      level of specific IgE against peanut extract and rAra h 2. CONCLUSION: Skin prick
      tests to individual recombinant peanut allergens appear to be a safe and
      effective diagnostic tool. Cosensitization to rAra h 2 and rArah 1 and/or rAra h
      3 is predictive of more severe reactions. CLINICAL IMPLICATIONS: Recombinant
      peanut allergens can be used by SPTs for diagnosis and evaluation of allergy
      severity.

PMID- 16815165
TI  - Generation of hypoallergenic DNA vaccines by forced ubiquitination: preventive
      and therapeutic effects in a mouse model of allergy.
AB  - BACKGROUND: Hypoallergenic immunotherapy of type I allergies aims at inducing T
      cell immunity while avoiding cross-linking of pre-existing IgE. DNA-based
      immunotherapy depends on the recruitment of antigen-specific T(H)1 cells and
      therefore has to provide the whole repertoire of T-cell epitopes. Ubiquitination
      offers a general approach for the production of hypoallergenic DNA vaccines.
      OBJECTIVE: A DNA-based vaccine encoding the major birch pollen allergen Bet v 1
      stably linked to ubiquitin was evaluated for its antiallergic potential in a
      BALB/c mouse model of allergy. METHODS: Plasmid DNA was applied to mice before
      (preventive) or after (therapeutic) sensitization with recombinant Bet v 1. In
      the preventive setting, mice were exposed to aerosolized allergen in addition.
      Cytokine production was monitored via ELISPOT and Luminex. IgG(1), IgG(2a), and
      IgE subclass antibody titers were determined by ELISA. In vitro antigen-specific
      cross-linking of IgE was measured in a degranulation assay. Bronchoalveolar
      lavages were analyzed for leukocyte subsets as well as for IFN-gamma and IL-5,
      and paraffin sections of lungs were examined for mucus production and endothelial
      damage. RESULTS: Prevaccination with ubiquitinated Bet v 1-stimulated T(H)1
      biased immune responses with concomitant suppression of functional IgE, reduction
      of eosinophil counts in bronchoalveolar lavages, and alleviation of lung
      pathology, and could also suppress an ongoing IgE response in a therapeutic
      setting. CONCLUSION: The data clearly demonstrate that hypoallergenic DNA
      vaccines encoding ubiquitin fusion constructs induce effective antiallergic
      immune responses. CLINICAL IMPLICATIONS: Ubiquitination of allergen gene vaccines
      eliminates the risk of IgE cross-linking, thereby meeting the safety requirements
      for clinical applications.

PMID- 16815164
TI  - Resistin-like molecule beta regulates innate colonic function: barrier integrity
      and inflammation susceptibility.
AB  - BACKGROUND: Resistin-like molecule (RELM) beta is a cysteine-rich cytokine
      expressed in the gastrointestinal tract and implicated in insulin resistance and
      gastrointestinal nematode immunity; however, its function primarily remains an
      enigma. OBJECTIVE: We sought to elucidate the function of RELM-beta in the
      gastrointestinal tract. METHODS: We generated RELM-beta gene-targeted mice and
      examined colonic epithelial barrier function, gene expression profiles, and
      susceptibility to acute colonic inflammation. RESULTS: We show that RELM-beta is
      constitutively expressed in the colon by goblet cells and enterocytes and has a
      role in homeostasis, as assessed by alterations in colon mRNA transcripts and
      epithelial barrier function in the absence of RELM-beta. Using acute colonic
      inflammatory models, we demonstrate that RELM-beta has a central role in the
      regulation of susceptibility to colonic inflammation. Mechanistic studies
      identify that RELM-beta regulates expression of type III regenerating gene (REG)
      (REG3beta and gamma), molecules known to influence nuclear factor kappaB
      signaling. CONCLUSIONS: These data define a critical role for RELM-beta in the
      maintenance of colonic barrier function and gastrointestinal innate immunity.
      CLINICAL IMPLICATIONS: These findings identify RELM-beta as an important molecule
      in homeostatic gastrointestinal function and colonic inflammation, and as such,
      these results have implications for a variety of human inflammatory
      gastrointestinal conditions, including allergic gastroenteropathies.

PMID- 16815166
TI  - Lack of association between Toll-like receptor 2 and Toll-like receptor 4
      polymorphisms and atopic eczema.

PMID- 16815167
TI  - Oral phenylephrine: an ineffective replacement for pseudoephedrine?

PMID- 16815168
TI  - Normal lung function in children with mild to moderate persistent asthma well
      controlled by inhaled corticosteroids.

PMID- 16815169
TI  - Continuous hydromorphone infusion for opioid intolerance.

PMID- 16815170
TI  - The interaction of IL1A and endothelial nitric oxide synthase polymorphisms is
      associated with the degree of atopy.

PMID- 16815171
TI  - Immunopathology of atopic dermatitis.

PMID- 16815173
TI  - Outpatient tonsillectomy in children: a systematic review.
AB  - OBJECTIVE: To evaluate the level of evidence regarding the safety of outpatient
      pediatric tonsillectomy. STUDY DESIGN AND SETTING: The medical literature
      addressing outpatient pediatric tonsillectomy was systematically reviewed. The
      level of evidence was assessed, and data were pooled. RESULTS: Seventeen articles
      met inclusion criteria. Each article suggested that outpatient tonsillectomy was
      safe. The overall level of evidence was fair (grade B-). Pooled data analysis in
      the perioperative period showed a complication rate estimate of 8.8% (95%
      confidence interval [CI], 5.5%-12.1%; P < or = 0.001) and an unplanned admission
      rate estimate of 8.0% (95% CI, 5.3%-10.7%; P < or = 0.001). Subgroup analysis
      suggests that children under age 4 are at a higher risk of complications in the
      perioperative period with an odds ratio of 1.64 (95% CI, 1.16-2.31). CONCLUSION:
      The level of evidence supporting the safety of outpatient pediatric tonsillectomy
      is fair. The analyzed data show a higher rate of early complications and
      unplanned admissions in children under age 4. SIGNIFICANCE: The current evidence
      supports the practice of outpatient tonsillectomy in properly selected children.
      EBM RATING: A-1a.

PMID- 16815174
TI  - Post-tympanostomy tube otorrhea: a meta-analysis.
AB  - INTRODUCTION: Post-tympanostomy tube otorrhea is the most common complication of
      tympanostomy tube placement. The incidence of this problem varies from 3.4% to
      74%. Trials that study post-tympanostomy tube otorrhea may involve valid
      randomization "by patient" or "by ear." In an attempt to define "best practice,"
      we conduct a meta-analysis to quantify the benefit of using topical prophylactic
      antibiotic drops in the postoperative period. We then compare our findings with
      previous results found in the literature. METHODS: We selected randomized studies
      for which antibiotic drops had been used for at least 48 hours after tympanostomy
      tube insertion. Nine studies, 3 "by ear" and 6 "by patient," met our inclusion
      criteria. The odds ratio and 95% confidence intervals were calculated for each to
      conduct the meta-analysis. RESULTS: Overall, prophylaxis appears to be effective
      at reducing the incidence of post-tympanostomy tube otorrhea. The odds ratios for
      all studies were less than 1.0. However, none of the 3 "by ear" studies and only
      3 of the 6 "by patient" studies were statistically significant. The mean odds
      ratio was 52%, suggesting that prophylaxis may reduce the incidence of post
      tympanostomy tube otorrhea by half. CONCLUSION: This meta-analysis suggests that
      routine post-tympanostomy tube prophylaxis is beneficial, but this finding is
      dependent on selection criteria used. EBM RATING: A-1a.

PMID- 16815175
TI  - Passive smoke exposure as a risk factor for airway complications during
      outpatient pediatric procedures.
AB  - OBJECTIVE: Determine if passive smoke exposure (PSE) increases airway
      complications during outpatient mask anesthesia procedures in children. METHODS:
      A prospective cohort of children who underwent surgical procedures under mask
      anesthesia was studied with the American Thoracic Society children's
      questionnaire on environmental and respiratory factors. Double-blinded outcomes
      with respect to adverse airway events were recorded both intraoperatively and in
      the recovery room for patients with and without passive smoke exposure.
      Multivariate comparisons assessing the likelihood of these airway complications
      were conducted between the PSE and nonexposed groups. RESULTS: Of 405 children,
      168 (41.5%) had PSE. The incidence of airway complications during anesthesia or
      postanesthetic recovery was higher for all outcome measures for PSE children (all
      P </= 0.005), except for recovery room breath holding (P = 0.086). Intraoperative
      laryngospasm and airway obstruction were 4.9 and 2.8 times more likely with PSE,
      respectively. CONCLUSIONS: PSE significantly increases the risk of anesthesia
      related airway complications during outpatient pediatric procedures. EBM RATING:
      A-1b.

PMID- 16815176
TI  - Sensory neuropathic cough: a common and treatable cause of chronic cough.
AB  - OBJECTIVE: To describe our experience with chronic sensory neuropathic cough and
      its response to amitriptyline in a first group of patients. STUDY DESIGN AND
      SETTING: A prospective cohort of patients is described in detail. Each was
      referred to an academic laryngological practice after extensive prior negative
      workup for cough and failure to respond to various treatments. Each of these
      patients was treated with amitriptyline and asked to report the effect on the
      cough at fixed intervals by means of telephone interviews. RESULTS: A first
      cohort of 12 consecutive patients with a chronic, nonproductive cough that lasted
      between 2 months and 20 years, with no (formerly) discernible cause is described.
      Purely clinical criteria of inclusion and exclusion are proposed. All patients
      had at least 40% reduction of self-reported symptoms, with most describing
      between 75% to 100% short-term relief. CONCLUSION: Sensory neuropathic cough can
      be diagnosed clinically in patients with chronic idiopathic cough. A trial of
      amitriptyline 10 mg or of other anti-neuralgia type medications may be helpful.
      Longer term and controlled trials are warranted to validate this entity and prove
      efficacy of neurologic medication in chronic sensory neuropathic cough. EBM
      RATING: C-4.

PMID- 16815177
TI  - Effect of local application of cidofovir on the control of recurrences in
      recurrent laryngeal papillomatosis.
AB  - OBJECTIVE: To study the effect of local application of cidofovir in patients with
      recurrent laryngeal papillomatosis (RLP) by measuring the interval between
      recurrences and the extent of disease at each recurrence. STUDY DESIGN AND
      SETTING: The study group included 10 patients with RLP. Videolaryngoscopic
      analysis of previous RLP operations for each patient before starting cidofovir
      and the number and timing of pre-cidofovir recurrences of the disease provided
      data for a self-control group. The cidofovir was injected with a laryngeal needle
      during papilloma resection operations. To evaluate the changes and the extent of
      the disease, the authors developed a staging system based on anatomic topography.
      The extent of the disease and the intervals between recurrences were analyzed and
      statistically compared. RESULTS: The median interval between recurrences
      significantly increased from 102 days before cidofovir to 239 days after
      treatment. No local or systemic side effects were observed. CONCLUSIONS: The
      study supports the hypothesis that cidofovir is an effective adjunct in treating
      recurrences of RLP. EBM RATING: C-4.

PMID- 16815179
TI  - Laryngeal reconstruction with porous high-density polyethylene.
AB  - OBJECTIVE: This study was undertaken to evaluate the use of the Medpor (Porex
      Surgical, College Park, GA) implant in laryngeal reconstruction and to discuss
      potential indications of this material in head and neck surgeries. METHOD: Twelve
      rabbits were used in this particular study. Laryngoplasties were performed by
      extracting 5 x 10-mm thyroid cartilage and replacing it with Medpor implant.
      Animals were sacrificed in the 1st, 2nd, and 4th weeks and 2, 6, and 9 months
      after implantation. The degree of fibrous capsule formation, histiocytic
      reaction, foreign body giant cell reaction, lymphocytic and neutrophilic
      reactions, vocal fold changes, and hyaline cartilage formation in the implant bed
      were evaluated. RESULTS: Fibrous capsule was formed around the implant in 2
      weeks. Four weeks after the implantation cellular reaction in the implant bed
      decreased significantly. Foreign body giant cell reaction was detected only the
      first 2 weeks after the implantation. CONCLUSION: According to the results of
      this study, the Medpor implant can be safely used in laryngeal reconstruction.

PMID- 16815178
TI  - Cross-linked hyaluronan-coated stents in the prevention of airway stenosis.
AB  - OBJECTIVE: This project studies the use of airway stents coated with a cross
      linked derivative of hyaluronan (HA) in a rabbit airway model of subglottic
      stenosis (SGS). STUDY DESIGN AND SETTING: An acute subglottic mucosal injury and
      airway stent placement design were used in a rabbit model. Thirty-six rabbits
      were randomized to 6 different study groups. Four groups had the subglottic
      mucosa denuded at the cricoid, and 2 groups received no injury. Airway stents
      coated with Carbylan-SX, a cross-linked derivative of HA, and controls were
      placed for 3 weeks. After sacrifice at 6 weeks, morphometric measurements of
      subglottic lumen were taken. RESULTS: In posttraumatic models, no significant
      differences were seen in airway area measures between groups (P = 0.86). In non
      injury groups, a significant difference between Carbylan-SX versus non-HA
      derivative-coated stents was seen (P = 0.05). CONCLUSION: In this model of acute
      subglottic mucosal injury, the HA-derivative-coated stent did not improve
      healing. However, in the absence of mucosal injury, the Carbylan-SX film-coated
      stent yielded significantly larger airway areas compared with a noncoated stent.
      SIGNIFICANCE: Stents or endotracheal tubes coated with a cross-linked derivative
      of HA may prevent stenosis in patients without airway injury but require long
      term intubation or laryngotracheal stenting.

PMID- 16815180
TI  - Reanimation of paralyzed laryngeal muscles by electrical stimulation synchronized
      with inspiration.
AB  - OBJECTIVE: To determine the effects of electrical stimulation on denervated cat
      posterior cricoarytenoid (PCA) muscle. STUDY DESIGN AND SETTING: This study was
      conducted on six cats with PCA muscle denervation. All animals were sacrificed 12
      weeks after surgery and the glottal area in the live animals and the fiber
      diameters of PCA muscle were obtained. RESULTS: Signals synchronized with
      inspiration were recorded and transmitted to stimulate PCA muscle. The abduction
      of the paralyzed vocal cord during inspiration was observed; this allows enough
      flow of air through the larynx to maintain the respiration. The stimulated fiber
      diameters of PCA muscle were different from that of nonstimulated (P < 0.01).
      Although all denervated muscles were degenerated, electrical stimulation was used
      to prevent muscular atrophy. CONCLUSIONS: This study indicates that electrical
      stimulation of the PCA muscle synchronized with inspiration could restore the
      abduction of a paralyzed vocal cord and prevent the denervated muscles from
      atrophying. SIGNIFICANCE: Electrical stimulation synchronized with inspiration
      may lead to reanimation of paralyzed laryngeal muscles.

PMID- 16815181
TI  - Vagal nerve stimulator implantation: an otolaryngologist's perspective.
AB  - OBJECTIVE: This study was conducted to compare an otolaryngologist's experience
      with a cohort of epilepsy patients implanted with a vagal nerve stimulator (VNS)
      to previously published data. METHODS: Demographics, preoperative seizure
      frequency, medications, and complications were retrospectively collected from
      patients implanted by the senior author. Postoperative medications and seizure
      frequency were obtained from referring neurologists. RESULTS: Seventeen patients
      were implanted over a 24-month period. Average age was 28.3 years. Patients
      presented with petit mal (n = 3), tonic-clonic (n = 6), complex partial (n = 5),
      and grand mal (n = 8) seizures. Mean follow-up postimplantation was 13.5 months.
      Most patients had at least a 50% reduction of seizure frequency, with 3 patients
      being seizure free. There were no postoperative infections. One patient had left
      vocal cord immobility. The most common side effect was voice disturbance during
      device activation. CONCLUSION: Otolaryngologists are well equipped to perform VNS
      implantation and to diagnose and treat possible laryngeal side effects. EBM
      RATING: C-4.

PMID- 16815182
TI  - The role of gastric Helicobacter pylori infection in laryngopharyngeal reflux
      disease.
AB  - OBJECTIVES: To investigate the role of Helicobacter pylori (H pylori) infection
      in laryngopharyngeal reflux (LPR). STUDY DESIGN: A prospective multidisciplinary
      clinical study. METHODS: Forty-four adult patients who applied to our ENT clinic
      with LPR symptoms were evaluated. Then these patients underwent upper
      gastrointestinal system endoscopy and double probe pH monitoring. In addition,
      during the endoscopy multiple biopsies from the stomach were obtained to detect H
      pylori. RESULTS: Results from 32 LPR positive patients were assessed (10 male and
      22 female). There were no statistically significant differences between the
      presence of H pylori and sex, age, degree of gastritis and esophagitis, and also
      the number of reflux, fractional acid exposure time regarding proximal probe
      readings. Similarly for both proximal and distal probe readings, the average
      score of esophageal acid clearance was not statistically significant (P > 0.05).
      In addition, no statistically significant difference was found between the
      presence of H pylori and GERD (P > 0.05). CONCLUSIONS: The results of this study
      demonstrated that there is no relationship between gastric H pylori infection and
      LPR. EBM RATING: B-3b.

PMID- 16815183
TI  - The effects of intradermal and topical mitomycin C on wound healing.
AB  - OBJECTIVE: To determine the effect of intradermal and topical mitomycin C (MMC)
      on skin wound healing. STUDY DESIGN/SETTING: A prospective, controlled study in a
      rat wound model performed in an academic medical center. RESULTS: Intradermal and
      topical MMC application decreased wound integrity when compared with saline
      treated animals at 1 week, 2 weeks, 1 month, and 6 months. Skin necrosis occurred
      in animals that received intradermal MMC. Hemotoxylin and eosin and
      immunohistochemical staining showed no consistent difference between treatment
      arms. Fibrosis and collagen deposition were reduced in MMC-treated wounds on
      trichrome staining. CONCLUSIONS: MMC-treated wounds showed decreased wound
      strength compared with controls. Intradermal MMC can cause skin necrosis.
      Histologic findings did not always correspond with clinical data. SIGNIFICANCE:
      The data suggest cautious use of MMC in clinical situations when wound breaking
      strength is critical.

PMID- 16815184
TI  - Differentiation plasticity of human fetal articular chondrocytes.
AB  - OBJECTIVE: To test chondrogenic differentiation potential, we examined the
      differentiation plasticity of isolated human fetal articular chondrocytes
      (HFACs). STUDY AND DESIGN SETTING: Culture-expanded human fetal articular
      chondrocytes (HFACs) were analyzed for chondrogenic, adipogenic, osteogenic
      capacity and neural differentiation ability in defined in vitro culture systems.
      RESULTS: The different assays demonstrated that culture-expanded HFACs have
      potential to form cartilage in pellet mass culture, to form adipose cells,
      osteogenic cells, and neural cells in monolayer culture. CONCLUSIONS: These
      results suggest that within human fetal articular cartilages there are MSC-like
      cells that exhibit differentiation plasticity that is comparable with that of BM
      MSCs and they may be a new kind of seeding cells for head and neck cartilage
      reconstruction.

PMID- 16815185
TI  - Nationwide survey on the use of image-guided functional endoscopic sinus surgery.
AB  - OBJECTIVE: To evaluate impressions and usage of sinus surgery image-guided
      surgical (IGS) systems by ENT surgeons in the United States. STUDY DESIGN AND
      SETTING: A survey was mailed to selected practicing ENT physicians, investigating
      regional information, practice type, IGS usage patterns, perceived benefits and
      limitations, and usage of the 61795 surgery code. RESULTS: Seventy-three percent
      of respondents use IGS. Nonusers respond that it provides no benefit or is too
      expensive. Eighty percent of respondents replied that IGS may allow for increased
      safety in certain procedures. Most users attempt reimbursement with the 61795
      code. CONCLUSION: IGS usage is increasing but appears to be perceived as
      expensive and nonbeneficial in certain situations. Most respondents, however,
      felt that IGS may lead to safer surgery in certain situations, including revision
      and frontal procedures. Several factors appear to limit routine use including
      ease of use, technical setup, code reimbursement, and initial purchase costs.
      SIGNIFICANCE: IGS use appears to be increasing. The most frequent users appear to
      agree with the previously issued AAO-HNS guidelines regarding appropriate
      indications. Expanded use may depend on ease of use, reimbursement, and
      affordability. EBM RATING: D-5.

PMID- 16815186
TI  - Image-guidance technology: what type of information best guides its appropriate
      use?

PMID- 16815188
TI  - Long-term results of endonasal laser dacryocystorhinostomy.
AB  - OBJECTIVE: To determine the long-term success rate of endonasal laser
      dacryocystorhinostomy (DCR) in our unit. MATERIALS AND METHODS: This was a
      retrospective study including all the consecutive cases of endonasal laser DCR
      (ELDCR) between November 1996 and December 1999. Patients who underwent revision
      DCR were excluded. The absence or improvement of symptoms as reported by the
      patients was defined as successful outcome. Conversely, recurrence of epiphora
      was considered as failure. The results were reviewed at 1 year in the clinic and
      at further 3 years and 5 years by telephone consultation. RESULTS: There were 65
      patients (73 procedures) in the study cohort, with a mean follow-up period of 74
      months (range, 60-97). Early failure was noted in 13 patients at 1 year. Only 28
      patients (of the possible 50) were free from epiphora after 5 years postsurgery.
      CONCLUSION: We found that the success rate of ELDCR has gradually declined over
      the years to 56% (confidence interval, 38-69) in patients who had at least 5
      years of postoperative data. We do not advocate the use of laser in endonasal DCR
      for patients with epiphora. EBM RATING: C-4.

PMID- 16815187
TI  - Quality of life and complications following image-guided endoscopic sinus
      surgery.
AB  - OBJECTIVES: To compare the quality of life (QOL) outcome and incidence of
      complications following image-guided versus non-image-guided endoscopic sinus
      surgery (ESS). STUDY DESIGN: The operative, office, and hospital charts of
      patients who underwent primary ESS for chronic sinusitis by a single surgeon with
      (2002-2005) or without (1997-2002) image guidance were reviewed for patient
      demographics, incidence of complications, and revision procedures. A telephone
      survey was used to administer the QOL survey to both cohorts. RESULTS: In
      comparing patients who underwent image-guided (60) versus non-image-guided
      surgery (179), respectively, there was no statistically significant difference in
      the incidence of major intraoperative complications (6.6% vs 5.6%), major
      postoperative complications (5% vs 3.9%), revision procedures (6.6% vs 7.3%), and
      postoperative SNOT-20 symptom scores (23.6 vs 23.4). A higher incidence of
      intraoperative cerebrospinal fluid leak was noted in the non-image-guided group
      (0% vs 2.2%). CONCLUSIONS: Our study does not demonstrate an improvement in the
      incidence of complications, need for revision procedures, or quality-of-life
      outcome for patients undergoing primary ESS for chronic sinusitis. The use of
      image guidance may result in a lower incidence of skull base trauma and
      cerebrospinal fluid leak. EBM RATING: B-2b.

PMID- 16815189
TI  - Preliminary findings for preemptive analgesia with inhaled morphine: efficacy in
      septoplasty and septorhinoplasty cases.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of inhaled morphine
      for preemptive analgesia in patients who undergo septoplasty or septorhinoplasty.
      STUDY PLAN AND METHODS: Eighty ASA I-II patients scheduled for septoplasty or
      septorhinoplasty were recruited and randomly divided into 2 groups that received
      different treatments 10 minutes prior to induction. The preemptive analgesia
      group (Group P, n = 40) received 65 mug kg(-1) morphine sulphate (a 3-mL volume)
      via an oral nebulizer, and the control group (Group C, n = 40) received 3 mL 0.9%
      sodium chloride (physiological saline) via the same type of nebulizer. Blood
      pressure, oxygen saturation, heart rate, time to first requirement for analgesia,
      and occurrence of nausea/vomiting were recorded. RESULTS: There were no
      significant differences between Groups P and C with respect to age, body weight,
      sex distribution, or duration of surgery. There was also no significant
      difference between the group frequencies of postoperative nausea/vomiting. The
      time to first requirement for analgesia was significantly longer in Group P than
      Group C. CONCLUSION: The results of this preliminary study suggest that a single
      dose of inhaled morphine administered preemptively prior to septoplasty or
      septorhinoplasty provides effective postoperative analgesia. EBM RATING: B-3b.

PMID- 16815190
TI  - Association of HLA-DR3 and HLA-DR4 with sinonasal polyposis in Mexican Mestizos.
AB  - OBJECTIVE: The pathogenesis of sinonasal polyposis (SNP) is not clear; it has
      been suggested that it is polygenic and multifactorial. The major
      histocompatibility complex is a useful tool to predict genetic susceptibility to
      diseases, especially to autoimmune diseases. Since such susceptibility is
      influenced by ethnicity, it is necessary to have a wide knowledge of the
      structure of the population to which the patient belongs. The purpose of the
      study was to determine the association of HLA-DRB1 alleles with sinonasal
      polyposis in the Mexican Mestizo population. STUDY DESIGN: We studied the HLA-DR
      alleles in 34 adult Mexican Mestizo patients with SNP and compared them to those
      present in 99 healthy controls. METHODS: Genomic DNA from mononuclear cells was
      obtained by using the "salting out" technique and high-resolution DNA typing of
      the HLA-DRB1 alleles was performed after PCR amplification. RESULTS: We found a
      statistically significant increased frequency of the HLA-DRB1*03 allele (P =
      0.03, odds ratio [OR] = 2.9, 95% confidence interval [CI]: 1.0-7.8) and of the
      HLA-DRB1*04 allele (P = 0.009, OR = 2.2, 95% CI: 1.2-4.2) in patients with SNP as
      compared to controls, and a statistically significant decreased frequency of the
      HLA-DRB1*08 allele (P = 0.01, OR = 0.2, 95% CI: 0.05-0.8). CONCLUSION: The HLA-DR
      locus seems to be associated with the genetic susceptibility to develop SNP in
      Mexicans. EBM RATING: B-2b.

PMID- 16815191
TI  - Hyperostosis may affect prognosis after primary endoscopic sinus surgery for
      chronic rhinosinusitis.
AB  - OBJECTIVE: To investigate the independent effect of hyperostosis on outcome after
      endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS).
      STUDY DESIGN AND SETTING: The medical records of 81 consecutive patients who had
      undergone primary ESS for CRS were reviewed retrospectively. Sinus CT scans were
      evaluated for the presence of hyperostosis to investigate the association with
      postoperative outcomes. The independent effect of hyperostosis on surgical
      outcome was analyzed, controlling for possible confounding factors with a
      multiple logistic regression model. RESULTS: Sixty percent of the patients showed
      hyperostosis, and there was a statistically significant association between the
      hyperostosis and postoperative outcome (P = 0.035, chi(2) test), which was
      confirmed after adjustment for the possible confounding factors (P = 0.048, odds
      ratio [OR] = 3.19, logistic regression analysis). CONCLUSIONS: Our study suggests
      that patients with CRS who have hyperostosis may have a poorer surgical outcome
      than those without hyperostosis. EBM RATING: B-2b.

PMID- 16815192
TI  - Estrogen blockade reduces auditory feedback in CBA mice.
AB  - OBJECTIVE: To examine the effects of estrogen suppression on age-related changes
      in distortion product otoacoustic emissions (DPOAEs) and contralateral
      suppression (CS) of DPOAEs in CBA mice. STUDY DESIGN AND SETTING: Young CBA mice
      received a slow-release shoulder implantation of either tamoxifen or placebo.
      Serial DPOAEs and CS of DPOAEs were obtained at 3-week intervals over a period of
      9 weeks. RESULTS: Although DPOAEs were maintained over the study interval, CS of
      DPOAEs decreased significantly with age in the experimental group. No such
      declines were observed in either the control animals or the untreated male mice.
      CONCLUSIONS: Estrogen suppression negatively affects the MOC efferent feedback
      system. SIGNIFICANCE: Our results support the hypothesis that estrogen plays an
      important role in the maintenance of auditory integrity. Additionally, our
      findings raise intriguing questions about auditory effects of hormonal shifts in
      humans resulting from menopause, hormone supplements such as oral contraceptives,
      and hormone replacement therapy as well as antiestrogens.

PMID- 16815193
TI  - Treatment of pediatric suppurative mastoiditis: is peripherally inserted central
      catheter (PICC) antibiotic therapy necessary?
AB  - OBJECTIVE: A review of the treatment of pediatric acute mastoiditis requiring
      surgical intervention managed with and without PICC therapy postoperatively.
      STUDY DESIGN AND SETTING: Retrospective study of 42 cases from 1989 to 2004
      treated at a regional children's hospital. RESULTS: Sixteen patients received
      postoperative PICC therapy and 26 received a course of oral antibiotics. The PICC
      group received on average 12.12 days of intravenous antibiotics compared to only
      3.53 days for the non-PICC group (P < 0.001). No differences were observed
      between the two groups in treatment outcomes. One patient from each group
      required rehospitalization. One minor complication was experienced in a patient
      in the PICC group. There were no surgical complications. The total cost for
      outpatient PICC therapy increased treatment costs by approximately $1500 to
      $2500. CONCLUSIONS: Oral antibiotic therapy is sufficient after surgical
      intervention for acute pediatric suppurative mastoiditis without intracranial
      complications and does not result in adverse treatment outcome. SIGNIFICANCE: Use
      of PICC therapy after surgical intervention for mastoiditis should be limited.
      EBM RATING: B-3b.

PMID- 16815194
TI  - Alpha1-antitrypsin single dose adjuvant therapy for acute otitis media.
AB  - OBJECTIVES: Proteases have been shown to play a role in the pathogenesis of
      otitis media. Inhibition of these proteases can improve treatment outcomes in
      certain conditions. The goal of this study was to determine if intratympanic
      administration of a single dose of the protease inhibitor, recombinant alpha 1
      antitrypsin (rAAT), can facilitate resolution of acute otitis media (AOM) in the
      chinchilla. METHODS AND MEASURES: Pneumococcus was injected into both middle ears
      of 12 chinchillas. After 3 to 4 days, middle ears were cultured, systemic
      antibiotics were initiated, and rAAT or its vehicle was administered into the
      middle ears of all animals. Serial tympanic membrane (TM) scoring, tympanometry,
      and auditory-evoked brain stem response testing were performed. Animals were
      sacrificed at varying timepoints and temporal bones studied for objective
      measures of OM. RESULTS: Although not reaching statistical significance, there
      was a trend to more rapid resolution of AOM in rAAT-treated ears. Tympanometry,
      auditory thresholds, and quantitative histologic parameters did not differ
      between rAAT and vehicle treated ears. CONCLUSIONS: A single dose of
      intratympanic rAAT likely does not facilitate the resolution of antibiotic
      treated pneumococcal AOM in the chinchilla model. Serial administration of this
      protease inhibitor may be necessary to see a significant treatment effect.

PMID- 16815195
TI  - Gerbilline cholesteatoma development Part III. Increased proliferation index of
      basal keratinocytes of the tympanic membrane and external ear canal.
AB  - OBJECTIVE: To quantify the rate of basal cell division for keratinizing
      epithelium (KE) of the tympanic membrane (TM) and external ear canal (EAC) in
      spontaneous and induced gerbilline cholesteatomas. STUDY DESIGN AND SETTING:
      Cholesteatomas (3 spontaneous and 5 by induction) were labeled with tritiated
      thymidine for autoradiography and a KE proliferation index (PI) was determined.
      The PI was defined as the average number of labeled cells/mm overall and per
      anatomic region. RESULTS: For all regions combined, the PI was 27.3 in ears with
      cholesteatoma and 4.1 in normal ears (P < 0.0001). Additionally, there were
      significant regional differences in the PI in both normal ears and ears with
      cholesteatoma. CONCLUSION: The KE of cholesteatomas in gerbils proliferates at
      approximately 7 times the rate measured in control ears. SIGNIFICANCE:
      Hyperproliferation of keratinocytes is a causative factor in the development and
      progression of spontaneous and experimental cholesteatomas in gerbils.

PMID- 16815196
TI  - Pigmented nevus of the external auditory canal.
AB  - OBJECTIVE: To present the clinical experience during an 18-year period of a
      series of 11 cases of pigmented nevus of the external auditory canal (EAC). STUDY
      DESIGN AND SETTING: Retrospective medical review of 11 consecutive patients with
      lesions seen in 2 departments of otolaryngology in Taiwan. RESULTS: 12 pigmented
      nevi, 2 to 12 mm (average, 6.4 mm) in diameter, were excised under otomicroscopy,
      and the EAC was packed with a temporary Penrose stent. One large lesion developed
      a postobstructive external auditory canal cholesteatoma (EACC). Histopathologic
      examination revealed 11 intradermal nevi and 1 compound nevus. There have been no
      recurrences or stenoses of EACs after 3 months to 17 years (average, 6 years) of
      follow-up. CONCLUSION: If a pigmented nevus causes symptoms, especially when it
      is large enough to obstruct the lumen of the EAC and has the possibility of
      developing into an EACC, it should be excised. EBM RATING: C-4.

PMID- 16815197
TI  - Reliability of interpretation of CT examination of the larynx in patients with
      glottic laryngeal carcinoma.
AB  - INTRODUCTION: Reports in literature suggest that tumor volume, cartilage
      invasion, and cartilage sclerosis are independent prognostic factors for tumor
      control in radiotherapy as primary treatment of laryngeal carcinomas. OBJECTIVE:
      Assessment of the interobserver variability and prognostic value in the
      measurement of tumor volume, cartilage invasion, and sclerosis. MATERIALS AND
      METHODS: Retrospective analysis of 55 CT scans by three independent observers.
      Volume measurements and determination of cartilage invasion, cartilage sclerosis,
      and tumor localization were calculated. Correlation between the prognostic
      factors and radiotherapy was calculated for each observer. RESULTS: Values for
      interobserver agreement varied substantially; cartilage invasion (kappa value: 
      0.02 to 0.66), cartilage sclerosis (kappa value: 0.13 to 0.57), tumor
      localization of subsites (kappa value: 0.03 to 0.60), and tumor volume
      (correlation: 0.34 to 0.73). The found interobserver variation makes it
      impossible to establish accurate prognostic factors. CONCLUSION: Determination of
      tumor volume, cartilage invasion, and cartilage sclerosis on the basis of CT
      imaging shows considerable interobserver variation; clinical significance appears
      to be limited. EBM RATING: B-3a.

PMID- 16815198
TI  - Amplification of CCND1, EMS1, PIK3CA, and ERBB oncogenes in ethmoid sinus
      adenocarcinomas.
AB  - OBJECTIVE: Assess the amplification of CCND1, EMS1, PIK3CA, ERBB1, and ERBB2
      oncogenes in ethmoid sinus adenocarcinomas. STUDY DESIGN AND SETTING: Tissue
      samples from 13 primary ethmoid adenocarcinomas and 2 recurrences were studied at
      Hospital Central de Asturias, Oviedo, Spain, between July 1998 and February 2002.
      A semiquantitative evaluation of CCND1, EMS1, PIK3CA, ERBB1, and ERBB2
      amplification was performed by multiplex polymerase chain reaction. RESULTS:
      Three (23%) cases presented CCND1 amplification, one of them with a concurrent
      PIK3CA amplification. EMS1 was amplified in the 2 studied recurrences. ERBB1 was
      amplified in 1 case (8%), whereas none presented ERBB2 amplification. Oncogenic
      amplifications were only detected in advanced (stage III) tumors; however, no
      prognostic value could be shown for them. CONCLUSIONS: CCND1, EMS1, PIK3CA, and
      ERBB1 amplifications are uncommon and appear to be late events in the development
      of ethmoid sinus adenocarcinoma. SIGNIFICANCE: New information on the
      carcinogenesis of this infrequent sinonasal tumor is presented.

PMID- 16815199
TI  - Postoperative radiation therapy for T1 and T2 primary parotid carcinoma: is it
      useful?
AB  - OBJECTIVE: The benefit of postoperative radiation for advanced primary parotid
      carcinoma has been reported previously, whereas studies to evaluate the
      usefulness of postoperative radiation for T1 and T2 parotid carcinomas have never
      been performed. STUDY DESIGN AND SETTING: Retrospective analysis on 58 previously
      untreated patients with T1 and T2 parotid carcinomas. In 34 patients,
      postoperative radiation was included in the treatment protocol and in 24
      patients, no postoperative radiation was applied. RESULTS: A local recurrence was
      observed in 8 of 24 (33%) patients without and in 1 of 34 (3%) patients with
      postoperative radiation (P < 0.5). The 5-year actuarial and disease-free survival
      rate was 83% and 70% for patients without postoperative radiation and 93% and 92%
      for patients with postoperative radiation. CONCLUSION AND SIGNIFICANCE: Local
      recurrence was less often observed in patients with postoperative radiation.
      Nevertheless, prospective randomized studies are needed to confirm the usefulness
      of postoperative radiation in early carcinomas. EBM RATING: B-3b.

PMID- 16815201
TI  - Office-based intralesional cidofovir injections for nasal septal papilloma: a
      pilot study.
AB  - OBJECTIVES: To determine if nasal septal papilloma is responsive to intralesional
      cidofovir injections. METHODS: Five adult males, ages 37 to 57, presented with
      nasal septal or columellar papilloma. Three lesions had been previously excised
      with the laser and recurred. The lesions were injected with cidofovir on a
      monthly basis until complete resolution or any residual lesion was excised
      afterwards with the laser. RESULTS: All patients achieved disease remission
      sustained over 10 to 24 months. Overall doses were much lower than those
      described for laryngeal papillomatosis and no toxic effects were observed.
      CONCLUSIONS: Office-based intralesional injections of cidofovir may show benefit
      in the treatment of nasal septal papilloma. EBM RATING: C-4.

PMID- 16815200
TI  - Inflammatory pseudotumor involving the skull base: response to steroid and
      radiation therapy.
AB  - OBJECTIVE: To evaluate the response to steroid and radiation therapy in
      inflammatory pseudotumor (IPT) involving the skull base. STUDY DESIGN AND
      SETTING: Eight patients with IPT of the skull base were evaluated. Six patients
      were diabetic. All patients underwent initial high-dose steroid therapy. Seven of
      8 patients underwent subsequent low-dose steroid maintenance. Additional low-dose
      radiation therapy was performed in 6 patients. We reviewed the medical records
      and radiologic findings of the patients to evaluate their responses to the
      steroid and radiation therapy. RESULTS: In all patients, the initial response to
      steroid therapy was fair. However, 7 patients showed symptom recurrence after
      cessation of steroid therapy. In 5 of 6 patients, low-dose radiation therapy
      resulted in recurrence. On follow-up MRI, none of the patients showed complete
      remission of the disease. CONCLUSION: This study shows aggressive clinical
      behavior of IPT involving the skull base and its poor response to steroid therapy
      and low-dose radiation therapy. For improving control, more aggressive initial
      efforts including high-dose radiation therapy with or without concurrent steroid
      therapy might play a role. EBM RATING: C-4.

PMID- 16815202
TI  - Long-term results with operated sinus tympani retraction cholesteatoma.
AB  - OBJECTIVES: Utilizing an endaural approach, we described the surgical treatment
      of 29 cases of sinus tympani retraction cholesteatoma in 1996. The purpose of
      this paper is to provide long-term results in this group of patients. STUDY
      DESIGN AND SETTING: A retrospective chart analysis of 29 previously reported
      patients was undertaken in an effort to identify hearing results and the risk of
      cholesteatoma recurrence following sinus tympani retraction surgery. RESULTS: The
      follow-up period ranged from 9 to 16 years (mean of 13.2 years). Speech
      discrimination (SD) and conductive hearing (CH) decline occurred in 23 of 28
      patients, but only on the average of 5.6% and 9 dB throughout the speech
      frequencies, respectively. Speech discrimination and conductive hearing improved
      in 5 of 28 patients; one patient was lost to follow-up. One patient developed a
      recurrent cholesteatoma requiring a canal wall-down mastoidectomy. CONCLUSIONS:
      The endaural approach for sinus tympani cholesteatoma provided stable hearing in
      most of the patients in this series. One cholesteatoma recurrence required
      conversion to a canal wall-down mastoidectomy. This developed in a noncompliant
      patient, whose pars tensa retraction deepened as a result of failure to have his
      ventilation tube replaced. Semiannual office visits are recommended in patients
      who undergo this otologic approach for sinus tympani cholesteatoma.

PMID- 16815203
TI  - Endoscopic optic nerve decompression for traumatic optic neuropathy: an
      alternative.

PMID- 16815204
TI  - Eccrine porocarcinoma of the ear mimicking basaloid squamous cell carcinoma.

PMID- 16815205
TI  - Laryngeal actinomycosis.

PMID- 16815206
TI  - Bone marrow metastasis in primary nasopharyngeal carcinoma.

PMID- 16815207
TI  - B-cell nasal lymphoma mimicking hyperplastic chronic rhinitis.

PMID- 16815208
TI  - Gradual nose enlargement: pachydermoperiostosis.

PMID- 16815209
TI  - T-cell primary cutaneous anaplastic large cell lymphoma mimicking appearance of
      large basal cell carcinoma.

PMID- 16815210
TI  - LigaSure device in parotid gland surgery.

PMID- 16815212
TI  - Systems biology: a primer.

PMID- 16815213
TI  - Molecular genetics of addiction vulnerability.
AB  - Classical genetic studies document strong complex genetic contributions to abuse
      of multiple addictive substances, to mnemonic processes that are likely to
      include those involved in substance dependence, and to the volumes of brain gray
      matter in regions that are likely to contribute to mnemonic/cognitive and to
      addictive processes. The working idea that these three heritable phenotypes are
      likely to share some of the same complex genetic underpinnings is presented. This
      review contains association-based molecular genetic studies of addiction that
      largely derive from my laboratory and their fit with linkage data from other
      laboratories. These combined results now identify many of the loci and genes that
      contain allelic variants that are likely to provide the heritable components of
      human addiction vulnerability. These data are also likely to have broad
      implications for neurotherapeutics. Drugs with potential abuse liabilities are
      widely used for indications that include pain, anxiety, sleep, seizure, and
      attentional disorders. There is increasing nonmedical use of these prescribed
      substances. Increasing information about addiction vulnerability gene variants
      should help to improve management of risks of dependence in individuals who
      receive such therapeutics. In addition, since mnemonic components that correlate
      well with individual differences in brain regional volumes are likely to play
      major roles in addiction processes, many addiction vulnerability genes are also
      good candidates to contribute to individual differences in mnemonic processes.
      Recently elucidation of addiction-associated haplotypes for the "cell adhesion"
      NrCAM gene illustrate several of these points.

PMID- 16815215
TI  - Microarrays in Parkinson's disease: a systematic approach.
AB  - Neurological disease (ND) is one of the greatest challenges facing our
      population, from medical, financial, and social perspectives. The application of
      new research approaches to understand the underlying pathogenesis of ND is
      critical. In this article, we review the use of microarray analysis in
      Parkinson's disease (PD). Microarrays have tremendous power, simultaneously
      querying the expression of tens of thousands of genes from a given biological
      sample. Coupled with impressive advances in statistical tools for analyzing
      large, complex data sets, well-designed microarray experiments are poised to make
      a big impact in the field of ND. Parkinson's disease is a devastating
      neurodegenerative disease well suited to a systems-based microarray analysis.
      Genetic and environmental rodent models of PD emulate many of the cardinal
      features of human PD, providing the unique opportunity to compare gene expression
      profiles from different etiologies of the same disease. The elucidation of
      important gene expression patterns during disease will make possible
      identification of genetic susceptibility markers, biomarkers of disease
      progression, and new therapeutic targets.

PMID- 16815216
TI  - Two-dimensional protein electrophoresis: from molecular pathway discovery to
      biomarker discovery in neurological disorders.
AB  - Two-dimensional protein electrophoresis (2-DE) has undergone many technical
      improvements in the past 30 years, resulting in an analytical method that is
      unparalleled in the resolution of complex protein mixtures and capable of
      quantifying changes in protein expression from a wide variety of tissues and
      samples. The technique has been applied in many studies of neurologic disease to
      identify changes in spot patterns that correlate with disease. The true power of
      the technique emerges when it is coupled to state-of-the-art methods in mass
      spectrometry, which enable identification of the protein or proteins contained
      within a spot of interest on a 2-DE map. Investigators have successfully applied
      the technique to gain improved understanding of neurologic disease mechanisms in
      humans and in animal models and to discover biomarkers that are useful in the
      clinical setting. An important extension to these efforts that has not been
      realized thus far is the desire to profile changes in protein expression that
      result from therapy to help relate disease-modifying effects at the molecular
      level with clinical outcomes. Here we review the major advances in 2-DE methods
      and discuss specific examples of its application in the study of neurologic
      diseases.

PMID- 16815217
TI  - Liquid chromatography with tandem mass spectrometry-based proteomic discovery in
      aging and Alzheimer's disease.
AB  - Systems biology offers enormous potential to understand the complexity of human
      brain aging and neurodegenerative diseases. Proteomics has an important role in
      these investigations because of its unique strengths and because of the potential
      central pathogenic contribution of pathological protein to several of these
      diseases. Here we have reviewed the methods and presented some examples of liquid
      chromatography-electrospray ionization-tandem mass spectrometry-based proteomics,
      with and without quantification using isotope-coded affinity tags, in the
      investigation of aging and Alzheimer's disease. As protocols and methods for
      improved quantitative high-throughput proteomics constantly improve, this
      approach will likely continue to provide deeper insight into human brain aging
      and neurodegenerative diseases.

PMID- 16815214
TI  - Single cell gene expression profiling in Alzheimer's disease.
AB  - Development and implementation of microarray techniques to quantify expression
      levels of dozens to hundreds to thousands of transcripts simultaneously within
      select tissue samples from normal control subjects and neurodegenerative diseased
      brains has enabled scientists to create molecular fingerprints of vulnerable
      neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is
      to sample gene expression from homogeneous cell types within a defined region
      without potential contamination by expression profiles of adjacent neuronal
      subpopulations and nonneuronal cells. The precise resolution afforded by single
      cell and population cell RNA analysis in combination with microarrays and real
      time quantitative polymerase chain reaction (qPCR)-based analyses allows for
      relative gene expression level comparisons across cell types under different
      experimental conditions and disease progression. The ability to analyze single
      cells is an important distinction from global and regional assessments of mRNA
      expression and can be applied to optimally prepared tissues from animal models of
      neurodegeneration as well as postmortem human brain tissues. Gene expression
      analysis in postmortem AD brain regions including the hippocampal formation and
      neocortex reveals selectively vulnerable cell types share putative pathogenetic
      alterations in common classes of transcripts, for example, markers of
      glutamatergic neurotransmission, synaptic-related markers, protein phosphatases
      and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of
      vulnerable regions and neurons may reveal important clues toward the
      understanding of the molecular pathogenesis of various neurological diseases and
      aid in identifying rational targets toward pharmacotherapeutic interventions for
      progressive, late-onset neurodegenerative disorders such as mild cognitive
      impairment (MCI) and AD.

PMID- 16815218
TI  - Redox proteomics in some age-related neurodegenerative disorders or models
      thereof.
AB  - Neurodegenerative diseases cause memory loss and cognitive impairment. Results
      from basic and clinical scientific research suggest a complex network of
      mechanisms involved in the process of neurodegeneration. Progress in treatment of
      such disorders requires researchers to better understand the functions of
      proteins involved in neurodegenerative diseases, to characterize their role in
      pathogenic disease mechanisms, and to explore their roles in the diagnosis,
      treatment, and prevention of neurodegenerative diseases. A variety of conditions
      of neurodegenerative diseases often lead to post-translational modifications of
      proteins, including oxidation and nitration, which might be involved in the
      pathogenesis of neurodegenerative diseases. Redox proteomics, a subset of
      proteomics, has made possible the identification of specifically oxidized
      proteins in neurodegenerative disorders, providing insight into a multitude of
      pathways that govern behavior and cognition and the response of the nervous
      system to injury and disease. Proteomic analyses are particularly suitable to
      elucidate post-translational modifications, expression levels, and protein
      protein interactions of thousands of proteins at a time. Complementing the
      valuable information generated through the integrative knowledge of protein
      expression and function should enable the development of more efficient
      diagnostic tools and therapeutic modalities. Here we review redox proteomic
      studies of some neurodegenerative diseases.

PMID- 16815220
TI  - The microarray data analysis process: from raw data to biological significance.
AB  - Despite advances in microarray technology that have led to increased
      reproducibility and substantial reductions in the cost of microarrays, the
      successful use of this technology is still elusive for many researchers, and
      microarray data analysis in particular presents a substantial bottleneck for many
      biomedical researchers. There are many reasons for this, including the expense of
      and a lack of adequate training in the use of analysis software. An additional
      reason is that microarray data analysis has largely been treated in the past as a
      set of separate steps, with the majority of emphasis being placed on statistical
      analysis and visualization of the data. For many biomedical researchers
      determining the biological significance of the data has been the greatest
      challenge and in the last several years more emphasis has been placed on this
      aspect of the analysis process. Despite this broadening of the scope of analysis
      there are still several aspects of the process that continue to be neglected,
      including additional related and interdependent aspects, such as experimental
      design, data accessibility, and platform selection. Though not traditionally
      thought of as integral to the data analysis process, these factors have profound
      effects on the analysis process. This article will discuss the importance of
      these additional aspects, as well as statistical analysis and determination of
      biological significance of microarray data. A summary of currently available
      software options will also be presented with a focus on the aspects discussed.

PMID- 16815219
TI  - The application of NMR-based metabonomics in neurological disorders.
AB  - Advances in postgenomic technologies have radically changed the information
      output from complex biological systems, generating vast amounts of high
      complexity data that can be interpreted by means of chemometric and bioinformatic
      methods to achieve disease diagnosis and prognosis. High-resolution nuclear
      magnetic resonance (NMR) spectroscopy of biofluids such as plasma, cerebrospinal
      fluid (CSF), and urine can generate robust, interpretable metabolic fingerprints
      that contain latent information relating to physiological or pathological status.
      This technology has been successfully applied to both preclinical and clinical
      studies of neurodegenerative diseases such as Huntington's disease, muscular
      dystrophy, and cerebellar ataxia. An extension of this technology, (1)H magic
      angle-spinning (HRMAS) NMR spectroscopy, can be used to generate metabolic
      information on small intact tissue samples, providing a metabolic link between
      metabolic profiling of biofluids and histology. In this review we provide a
      summary of high-resolution NMR studies in neurodegenerative disease and explore
      the potential of metabonomics in evaluating disease progression with respect to
      therapeutic intervention.

PMID- 16815221
TI  - Utility of correlation measures in analysis of gene expression.
AB  - The role of the correlation structure of gene expression data are two-fold: It is
      a source of complications and useful information at the same time. Ignoring the
      strong stochastic dependence between gene expression levels in statistical
      methodologies for microarray data analysis may deteriorate their performance.
      However, there is a host of valuable information in the correlation structure
      that deserves a closer look. A proper use of correlation measures can remedy
      deficiencies of currently practiced methods that are focused too heavily on
      strong effects in terms of differential expression of genes. The present paper
      discusses the utility of correlation measures in microarray data analysis and
      gene regulatory network reconstruction, along with various pitfalls in both
      research areas that have been uncovered in methodological studies. These issues
      have broad applicability to all genomic studies examining the biology, diagnosis,
      and treatment of neurological disorders.

PMID- 16815224
TI  - Infectious complications in patients with chronic kidney disease.

PMID- 16815222
TI  - The cognitive phenotype of Down syndrome: insights from intracellular network
      analysis.
AB  - Down syndrome (DS) is caused by trisomy of chromosome 21. All individuals with DS
      exhibit some level of cognitive dysfunction. It is generally accepted that these
      abnormalities are a result of the upregulation of genes encoded by chromosome 21.
      Many chromosome 21 proteins are known or predicted to function in critical
      neurological processes, but typically they function as modulators of these
      processes, not as key regulators. Thus, upregulation in DS is expected to cause
      only modest perturbations of normal processes. Systematic approaches such as
      intracellular network construction and analysis have not been generally applied
      in DS research. Networks can be assembled from high-throughput experiments or by
      text-mining of experimental literature. We survey some new developments in
      constructing such networks, focusing on newly developed network analysis
      methodologies. We propose how these methods could be integrated with creation and
      manipulation of mouse models of DS to advance our understanding of the perturbed
      cell signaling pathways in DS. This understanding could lead to potential
      therapeutics.

PMID- 16815225
TI  - Infectious complications in chronic kidney disease.
AB  - Infectious complications in individuals with chronic kidney disease (CKD) pose a
      significant source of morbidity and mortality. The overall scope of major
      infectious complications has, however, received little attention even though some
      of these events may be preventable. We reviewed infectious hospitalization rates
      in the CKD and end-stage renal disease (ESRD) populations, comparing them with
      the non-CKD and non-ESRD groups. We also reviewed preventive vaccination rates
      for influenza, pneumonia, and pneumococcal pneumonia to assess areas of potential
      improvement. We reviewed the medical literature and present findings based on
      hospitalization rates for pneumonia, sepsis/bacteremia, and urinary tract
      infections in the Medicare CKD, ESRD, and non-CKD populations. Vaccination rates
      were determined from submitted claims for services with specific codes for the
      vaccinations. Regardless of the primary cause for the development of CKD, primary
      kidney disease or secondary to hypertension, diabetes mellitus, or other chronic
      condition, patient outcomes after the development of infections were 3 to 4 times
      worse than in the non-CKD population. Influenza vaccination rates were 52%, far
      less than the target of 90%. Pneumococcal pneumonia vaccination rate was only
      13.5%, far less than recommended. CKD is associated with significant major
      infectious complications, which occur at rates 3 to 4 times the general
      population. Providers can improve prevention by using fewer dialysis catheters
      and increasing vaccination rates for influenza and pneumococcal pneumonia.

PMID- 16815226
TI  - Infections and cardiovascular disease in patients with chronic kidney disease.
AB  - Although interest in the nexus of cardiovascular disease and chronic kidney
      disease (CKD) has mushroomed, especially in the in past 5 years, activity in the
      arena of CKD-related infection has been much more modest. This development is
      surprising when one considers the increasing evidence that links inflammation,
      kidney disease, and cardiovascular disease. Also, major infections, such as
      pneumonia and septicemia, are paradigmatic inflammatory states, and accumulating
      evidence indicates that they are a common antecedent of new cardiovascular events
      in dialysis patients. Major infections are associated with higher rates of
      cardiovascular events and death in dialysis patients, and similar associations
      have been observed in community settings. Although recent studies suggest that
      hospitalization for major infections is much more common in nondialysis CKD than
      in the general population, the prognostic implications remain unexplored.

PMID- 16815227
TI  - Overview of vaccination in chronic kidney disease.
AB  - Infections are a major cause of death in end-stage renal disease (ESRD) patients,
      second only to cardiovascular disease, and also contribute to significant
      morbidity in patients with earlier stages of chronic kidney disease (CKD).
      Vaccines are a strategy to attempt to reduce morbidity related to infections.
      Patients with CKD and ESRD may not respond as well to vaccines as patients
      without kidney failure, but adequate seroresponse with standard or augmented
      regimens for vaccinations against influenza, hepatitis B, pneumococcus, and
      varicella have been documented. Influenza, in particular, seems to provide
      adequate protection with standard dosing regimens. Despite somewhat reduced
      effectiveness of certain vaccines in patients with CKD, there is emerging
      evidence of benefit to vaccination in these populations. However, vaccination
      rates are relatively low. Given the accumulating evidence of benefit, continuing
      quality improvement programs focused on increasing vaccination rates in patients
      with all levels of CKD are needed.

PMID- 16815228
TI  - Biofilm: its relevance in kidney disease.
AB  - Biofilm/bioslime is a complex, dynamically interactive multicellular community
      protected within a heterogeneous exopolysaccharide matrix. Its formation results
      in the genesis or perpetuation of infection, enhancement of inflammation, and
      tissue damage or death. Industrial financial losses result from biofilm/bioslime
      formation; however, the consequences in the medical realm are equally
      devastating. The relation of biofilm to patients with chronic kidney disease is
      often covert and extends beyond the colonization of hemodialysis circuits and
      vascular accesses. Urinary tract device- and vascular access-related biofilms may
      also increase the burden of cardiovascular risk borne by chronic kidney disease
      patients, synergizing with the chronic inflammatory state already incurred by
      these individuals. Current anti-infective strategies are aimed at rapidly killing
      planktonic forms of microorganisms without specifically targeting the sessile
      forms that perpetuate their planktonic brethren. Future treatments of infections
      must ultimately target these reservoirs of infection aiming for their complete
      eradication. Presently, included among these novel weapons of microdestruction
      are molecular blockading techniques, electrical enhancement of anti-infectives,
      and bacterial interference. Nonetheless, the best approach against biofilm
      formation remains the prevention of microbial colonization, which can be largely
      by sterile handling of patient-related devices, the most well-established biofilm
      reservoirs.

PMID- 16815229
TI  - Avoiding trouble down the line: the management and prevention of hemodialysis
      catheter-related infections.
AB  - Over the last 2 decades, hemodialysis catheter use has increased. Annually,
      approximately 30% of patients using a central venous catheter (CVC) experience a
      septic or bacteremic episode and are subsequently at risk of its associated long
      term complications and mortality. Because of the serious clinical and financial
      impact of hemodialysis catheter-related bacteremias (HCRIs), standardized,
      validated definitions based on the hemodialysis patient population are necessary
      in order to better diagnose, monitor, and report HCRI for patient quality
      assurance and research purposes. The pathophysiology of HCRI involves a complex
      interaction between a triad that consists of the host patient, the infecting
      microorganism, and the vehicle catheter. Although the microorganism contribution
      in the pathogenesis of HCRI is likely most important, certain patient and
      catheter-related characteristics may be more amenable to manipulation. The key to
      managing HCRI is on prophylaxis against the initial microorganism catheter
      adherence and subsequent biofilm development. General and specific prophylactic
      maneuvers directed at both an intravascular and extraluminal route of
      microorganism entry are discussed including antibiotic- and silver-impregnated
      catheters and dressings, subcutaneous access devices, and topical prophylaxis at
      the exit site. In addition to systemic antibiotic use, the 3 methods of HRCI
      treatment using catheter salvage, guidewire exchange, and concurrent antibiotic
      lock are compared. The outcome and complications of HCRI may be serious and
      highlight the importance of careful, continual infection surveillance. Although
      the use of a multidisciplinary hemodialysis infection control team is desirable,
      staffing education and physician feedback have been shown to improve adherence to
      infection control guidelines and reduce HCRI.

PMID- 16815230
TI  - Antimicrobial locks: putting the lock on catheter infections.
AB  - Infectious complications resulting from catheter use in the hemodialysis
      population remain as the significant cause of morbidity and mortality in this
      patient population. Because conservation of vascular access sites remains a
      therapeutic mainstay for chronic hemodialysis patients, clinical investigators
      have evaluated the safety and efficacy of catheter preservation with
      antimicrobial lock solutions instilled into the lumens of catheters to treat and
      prevent infectious complications. The recommended treatment of catheter-related
      bacteremia includes administration of systemic antibiotics with catheter removal.
      To date, 4 studies in the hemodialysis population have evaluated the use of
      systemic antibiotics with an antimicrobial lock solution for treatment of
      catheter-related bacteremias to amplify the success of catheter salvage. The use
      of antimicrobial lock solutions for the treatment of catheter-related bacteremia
      has resulted in successful catheter salvage in approximately 69% of patients,
      with the remainder requiring catheter removal following a lack of clinical
      improvement after 48 hours. The antimicrobial lock has also been studied as a
      prophylactic measure to prevent catheter-related bacteremia. Six studies in the
      hemodialysis population have evaluated the use of an antimicrobial lock for the
      prevention of catheter-related bacteremia with an overall 64%-100% reduction in
      the frequency of catheter-related bacteremia. Although the use of antimicrobial
      lock for prophylaxis has demonstrated efficacy in clinical trials, its long-term
      consequences, including potential impact on antimicrobial resistance, are
      unknown. The objectives of this review are to evaluate the current body of
      evidence espousing the utilization of an antimicrobial lock solution in tunneled
      cuffed and uncuffed catheters that are utilized during chronic intermittent
      hemodialysis.

PMID- 16815231
TI  - Optimizing antimicrobial therapy for gram-positive bloodstream infections in
      patients on hemodialysis.
AB  - Infections with gram-positive organisms are highly prevalent in hemodialysis
      patients and are a major cause of morbidity and mortality in this population.
      Antimicrobial therapy is widely used to treat these infections, and prolonged
      therapy with these agents is often necessary. Extensive use of antimicrobials in
      hemodialysis patients has resulted in a growing threat of resistance, especially
      among gram-positive bacteria such as Enterococcus spp and Staphylococcus aureus.
      Vancomycin-resistant enterococci and S. aureus isolates with reduced
      susceptibility to vancomycin are increasingly being reported in hemodialysis
      patients. Additionally, resistance of these organisms to newer agents, such as
      linezolid and daptomycin, has been documented. Appropriate utilization of
      antimicrobial therapy to treat these organisms requires an understanding of the
      pharmacokinetic and pharmacodynamic principles to optimize therapy and avoid
      adverse drug events. The pharmacokinetic and pharmacodynamic profile of
      antimicrobial agents can be significantly altered in patients with chronic kidney
      disease. This review will describe mechanisms of antimicrobial resistance among
      common gram-positive organisms. The pharmacokinetic and pharmacodynamic
      principles of cephalosporins, vancomycin, aminoglycosides, linezolid, and
      daptomycin and applications for use of these agents in the treatment of patients
      with bloodstream infections on hemodialysis are discussed.

PMID- 16815232
TI  - Diagnosis and management of enteric disease and abdominal catastrophe in
      peritoneal dialysis patients with peritonitis.
AB  - Peritoneal dialysis (PD)-associated peritonitis rates have decreased
      significantly in recent years, especially Staphylococcus epidermidis and
      Staphylococcus aureus infections. Rates of gram-negative, polymicrobial, and
      fungal peritonitis have remained steady. The reported mortality of gram-negative
      and polymicrobial peritonitis varies widely (4%-50%). Most likely, the reason for
      this variability is that prognosis depends on the underlying etiology more than
      the specific microorganisms isolated. Gram-negative, polymicrobial, and fungal
      infection have variable association with documented visceral disease, and the
      highest mortality occurs in reports with the highest prevalence of intra
      abdominal pathology. The odds ratio of death in PD patients with documented
      abdominal catastrophe and peritonitis is reported to be 20:1 compared with all
      other causes. Further reductions in PD-associated peritonitis mortality are
      likely to depend on earlier diagnosis and better management of intra-abdominal
      pathology. Presentation with hypotension, sepsis, lactic acidosis, and/or
      elevation of peritoneal fluid amylase should raise immediate concern for
      "surgical" peritonitis. Suspicion for visceral disease should also be high in
      patients with gram-negative, polymicrobial, and fungal infection or those who
      fail to improve rapidly as judged by clinical signs and symptoms, cell counts,
      and repeat cultures. Nonlocalizing physical examination and negative or
      nonspecific results of abdominal computed tomography do not rule out serious
      intra-abdominal disease. Immediate initiation of broad antibiotic coverage
      including for anaerobic infection is indicated when bowel pathology is suspected.
      Urgent surgical consultation, with active discussion and participation by the
      nephrologist, is advisable when visceral pathology is suspected and the patient
      is unstable or fails to improve rapidly.

PMID- 16815233
TI  - Infectious complications in renal transplant recipients.
AB  - Post-kidney transplant infection is the most common life-threatening complication
      of long-term immunosuppressive therapy. Optimal immunosuppression, in which a
      balance is maintained between prevention of rejection and avoidance of infection,
      is the most challenging aspect of posttransplantation care. The study of
      infectious complications in immunologically compromised recipients is changing
      rapidly, particularly in the fields of prophylactic and preemptive strategies,
      molecular diagnostic methods, and antimicrobial agents. In addition, emerging
      pathogens such as BK polyomavirus and West Nile flavivirus infections and the
      introduction of newer immunosuppressive agents that constantly change the risk
      profiles for opportunistic infections has added layers of complexity to this
      burgeoning field. Although remarkable progress has been made in these
      disciplines, comprehensive understanding of the clinical manifestations of
      infections remains limited, and the standardization of prophylaxis, diagnosis,
      and treatment of most infections is yet inadequately defined. The long-term goal
      for optimal care of transplant recipients, with respect to infection, is the
      prevention and/or early recognition and treatment of infections while avoiding
      drug-related toxicities.

PMID- 16815234
TI  - Developing an in-house resource for clinical social work services in the dialysis
      setting: a pilot program.
AB  - In 2005, the Renal Care Group's social work department in Arizona launched a
      pilot program to show the viability of an in-house resource for clinical social
      work services to address depression and treatment adherence among hemodialysis
      patients. Sixty-three participants were divided into an intervention group that
      was counseled by a licensed clinical social worker over a span of 3 months and a
      comparison group that received no additional services. Quantitative data were
      collected by using the Center for Epidemiological Studies-Depression scale, the
      short form of the Kidney Disease Quality of Life survey, and attendance records.
      Qualitative data were collected as narrative descriptions of patients' reasons
      for missing treatment time, their readiness for change, and the benefits they
      observed with improved adherence. Although no significant differences in outcomes
      were found between the intervention and comparison groups, women and patients
      with catheters were significantly more depressed than men and patients with
      fistulas. The qualitative data indicated that loss of confidence in the
      healthcare team undermined adherence even though patients described the potential
      benefits of dialysis in terms of increased energy, emotional well-being, and the
      ability to resume familiar activities. The findings supported the feasibility of
      establishing a clinical role within the social work department that would be
      dedicated to clinical social work practice in the dialysis setting.

PMID- 16815235
TI  - HIV-associated nephropathy.
AB  - Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is one of the
      most important causes of progressive kidney failure in HIV-1-seropositive
      patients. Since the 1980s, much has been published regarding the epidemiology,
      pathogenesis, and treatment of HIVAN. Our knowledge of the clinical features,
      pathologic manifestations, course, and potential outcome of HIVAN has increased
      considerably. The use of highly active antiretroviral therapy has shown
      significant improvement in the outcome of human immunodeficiency virus infection
      and is found to be effective in preventing end-stage renal disease. The purpose
      of this review is to summarize the data about the clinical manifestations,
      pathogenesis and pathophysiologic mechanisms of HIVAN with particular attention
      on treatment including pharmaceutical and renal replacement options.

PMID- 16815236
TI  - Nephrotoxicity as a complication of antiretroviral therapy.
AB  - Since 1984, human immunodeficiency virus-associated nephropathy has been
      established as a clinical entity that presents with nephrotic syndrome and
      progressive kidney failure. The pathological description is usually consistent
      with a collapsing form of focal segmental glomerulosclerosis. Podocytes and renal
      tubular cells have been proposed as a reservoir for the human immunodeficiency
      virus. This nephropathy is the third leading cause of end-stage renal disease in
      the population of African descent. It is documented that highly active
      antiretroviral therapy (HAART) successfully reverses or at least controls
      nephropathy in HIV-positive patients. The success of the treatment of HIV
      nephropathy now poses 2 problems to nephrologists: (1) an increased population of
      HIV-positive patients with chronic kidney disease not yet on dialysis and (2)
      potential nephrotoxicity of antiretroviral medications as well as medications
      used to treat opportunistic infections. HAART is defined by the combination of 2
      reverse transcriptase inhibitors with a protease inhibitor or 3 reverse
      transcriptase inhibitors. Many of these antiretrovirals have well-defined
      nephrotoxic effects. The objective of this text is to review data pertaining to
      some of the most common antiretrovirals (ARTs) and include information regarding
      nephrotoxicity of the medications frequently used to combat opportunistic
      infections. ARTs included in the review are (1) nucleoside reverse-transcriptase
      inhibitors (zidovudine and didanosine), (2) nucleotide reverse transcriptase
      inhibitors (adefovir and tenofovir), (3) the protease inhibitors (indinavir and
      saquinavir), and (4) the HIV fusion inhibitors.

PMID- 16815237
TI  - [Malignant hereditary paraganglioma: problems raised by non-functional forms
      management].
AB  - Non-functional paraganglioma have not clinical or biological characteristics, so
      that the diagnostic is most of the time delayed and made on the occasion of
      advanced abdominal tumor or symptomatic metastasis management. Hereditary forms,
      notably those with SDHB mutation, seem to have a poor prognosis. On the other
      hand, and on the oposite to sporadic forms, they are the only ones to benefit
      from genetic testing which make possible, if positive, an earlier diagnostic,
      before apparition of symptoms, recurrence or metastasis. We report a case of non
      functional malignant hereditary paraganglioma diagnosed belatedly and we will
      consider management problems raised by non-functional forms.

PMID- 16815238
TI  - Antimicrobial barrier of an in vitro oral epithelial model.
AB  - OBJECTIVE: Oral epithelia function as a microbial barrier and are actively
      involved in recognizing and responding to bacteria. Our goal was to examine a
      tissue engineered model of buccal epithelium for its response to oral bacteria
      and proinflammatory cytokines and compare the tissue responses with those of a
      submerged monolayer cell culture. DESIGN: The tissue model was characterized for
      keratin and beta-defensin expression. Altered expression of beta-defensins was
      evaluated by RT-PCR after exposure of the apical surface to oral bacteria and
      after exposure to TNF-alpha in the medium. These were compared to the response in
      traditional submerged oral epithelial cell culture. RESULTS: The buccal model
      showed expression of differentiation specific keratin 13, hBD1 and hBD3 in the
      upper half of the tissue; hBD2 was not detected. hBD1 mRNA was constitutively
      expressed, while hBD2 mRNA increased 2-fold after exposure of the apical surface
      to three oral bacteria tested and hBD3 mRNA increased in response to the non
      pathogenic bacteria tested. In contrast, hBD2 mRNA increased 3-600-fold in
      response to bacteria in submerged cell culture. HBD2 mRNA increased over 100-fold
      in response to TNF-alpha in the tissue model and 50-fold in submerged cell
      culture. Thus, the tissue model is capable of upregulating hBD2, however, the
      minimal response to bacteria suggests that the tissue has an effective
      antimicrobial barrier due to its morphology, differentiation, and defensin
      expression. CONCLUSIONS: The oral mucosal model is differentiated, expresses hBD1
      and hBD3, and has an intact surface with a functional antimicrobial barrier.

PMID- 16815239
TI  - Free energy profiles for H+ conduction in the D-pathway of Cytochrome c Oxidase:
      a study of the wild type and N98D mutant enzymes.
AB  - The molecular mechanism for proton conduction in the D-pathway of Cytochrome c
      Oxidase (CcO) is investigated through the free energy profile, i.e., potential of
      mean force (PMF) calculations of both the native enzyme and the N98D mutant. The
      multistate empirical valence bond (MS-EVB) model was applied to simulate the
      interaction of an excess proton with the channel environment. In the study of the
      wild type enzyme, the PMF reveals the previously proposed proton trap inside the
      channel; it also shows a high free energy barrier against the passage of proton
      at the entry of the channel, where two conserved asparagines (ASN80/98) may be
      essential for the gating of proton uptake. We also present data from an
      investigation of the N98D mutant, which has been previously shown to completely
      eliminate proton pumping but significantly enhance the oxidase activity in
      Rhodobacter sphaeroides. These results suggest that mutating Asn98 to negatively
      charged aspartate will create an unfavorable energy barrier sufficiently high to
      prevent the overall proton uptake through the D-pathway, whereas with a
      protonated aspartic acid the proton conduction was found to be accelerated.
      Plausible explanations for the origin of the uncoupling of proton pumping from
      the oxidase activity will be discussed.

PMID- 16815240
TI  - A Fourier transform infrared microspectroscopic imaging investigation into an
      animal model exhibiting glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is a highly malignant human brain tumour for which
      no cure is available at present. Numerous clinical studies as well as animal
      experiments are under way with the goal being to understand tumour biology and
      develop potential therapeutic approaches. C6 cell glioma in the adult rat is a
      frequently used and well accepted animal model for the malignant human glial
      tumour. By combining standard analytical methods such as histology and
      immunohistochemistry with Fourier Transform Infrared (FTIR) microspectroscopic
      imaging and multivariate statistical approaches, we are developing a novel
      approach to tumour diagnosis which allows us to obtain information about the
      structure and composition of tumour tissues that could not be obtained easily
      with either method alone. We have used a "Stingray" FTIR imaging spectrometer to
      analyse and compare the compositions of coronal brain tissue sections of a tumour
      bearing animal and those from a healthy animal. We have found that the tumour
      tissue has a characteristic chemical signature, which distinguishes it from
      tumour-free brain tissue. The physical-chemical differences, determined by image
      and spectral comparison are consistent with changes in total protein absorbance,
      phosphodiester absorbance and physical dispersive artefacts. The results indicate
      that FTIR imaging analysis could become a valuable analytic method in brain
      tumour research and possibly in the diagnosis of human brain tumours.

PMID- 16815241
TI  - Reciprocal inhibition of Cd(2+) and Ca(2+) uptake in human intestinal crypt cells
      for voltage-independent Zn-activated pathways.
AB  - Cadmium-Ca-Zn interactions for uptake have been studied in human intestinal crypt
      cells HIEC. Our results failed to demonstrate any significant cross-inhibition
      between Cd and Ca uptake under single metal exposure conditions. However, they
      revealed a strong reciprocal inhibition for a Zn-stimulated mechanism of
      transport. Optimal stimulation was observed under exposure conditions that favor
      an inward-directed Zn gradient, suggesting activation by extracellular rather
      than intracellular Zn. The effect of Zn on the uptake of Ca was concentration
      dependent, and zinc-induced stimulation of Cd uptake resulted in a 3- and 5.8
      fold increase in the K(m) and V(max) values, respectively. Neither basal nor Zn
      stimulated Ca uptakes were sensitive to membrane depolarization. However, the
      stimulated component of uptake was inhibited by the trivalent cations Gd(3+), and
      La(3+) and to a lesser extent by Mg(2+) and Ba(2+). RT-PCR analysis as well as
      uptake measurement performed with extracellular ATP and/or suramin do not support
      the involvement of purinergic P2X receptor channels. Uptake and fluorescence data
      led to the conclusion that Zn is unlikely to trigger Ca influx in response to Ca
      release from thapsigargin-sensitive intracellular pools. Our data show that Zn
      may potentiate Cd accumulation in intestinal crypt cells through mechanism that
      still needs to be clarified.

PMID- 16815242
TI  - Fourier transform infrared imaging spectroscopy investigations in the
      pathogenesis and repair of cartilage.
AB  - Significant complications in the management of osteoarthritis (OA) are the
      inability to identify early cartilage changes during the development of the
      disease, and the lack of techniques to evaluate the tissue response to
      therapeutic and tissue engineering interventions. In recent studies several
      spectroscopic parameters have been elucidated by Fourier transform infrared
      imaging spectroscopy (FT-IRIS) that enable evaluation of molecular and
      compositional changes in human cartilage with progressively severe OA, and in
      repair cartilage from animal models. FT-IRIS permits evaluation of early-stage
      matrix changes in the primary components of cartilage, collagen and proteoglycan
      on histological sections at a spatial resolution of approximately 6.25 microm. In
      osteoarthritic cartilage, the collagen integrity, monitored by the ratio of peak
      areas at 1338 cm(-1)/Amide II, was found to correspond to the histological Mankin
      grade, the gold standard scale utilized to evaluate cartilage degeneration.
      Apparent matrix degradation was observable in the deep zone of cartilage even in
      the early stages of OA. FT-IRIS studies also found that within the territorial
      matrix of the cartilage cells (chondrocytes), proteoglycan content increased with
      progression of cartilage degeneration while the collagen content remained the
      same, but the collagen integrity decreased. Regenerative (repair) tissue from
      microfracture treatment of an equine cartilage defect showed significant changes
      in collagen distribution and loss in proteoglycan content compared to the
      adjacent normal cartilage, with collagen fibrils demonstrating a random
      orientation in most of the repair tissue. These studies demonstrate that FT-IRIS
      is a powerful technique that can provide detailed ultrastructural information on
      heterogeneous tissues such as diseased cartilage and thus has great potential as
      a diagnostic modality for cartilage degradation and repair.

PMID- 16815243
TI  - Relative contribution of OAT1 and OAT3 transport activities in isolated perfused
      rabbit renal proximal tubules.
AB  - The expression of both OAT1 and OAT3 along the isolated rabbit renal proximal
      tubule (RPT) was determined using RT-PCR. They were found to be very strong in S2
      segment and weak in S1 and S3 segments. We further examined the relative
      transport activity of these transporters in isolated perfused rabbit RPT using
      [(3)H]para-aminohippurate ([(3)H]PAH), and estrone sulfate ([(3)H]ES) as specific
      substrates for rbOAT1 and rbOAT3, respectively. The transport activity of OAT1
      was in the order S2>S1=S3 segments and that of OAT3 was in the order S1=S2>>S3
      segments. The addition of alpha-ketoglutarate (100 muM) in the bathing medium
      increased both OAT1 and OAT3 transport activities in all segments of proximal
      tubule. The kinetics of [(3)H]succinic acid transport, used to measure the
      activity of sodium dicarboxylate transporter 3 (NaDC3), were examined. The J(max)
      for succinic acid was in the order S2>S3 and unmeasurable in the S1 segment. Our
      data indicate that both OAT1 and OAT3 play quantitatively significant roles in
      the renal transport of organic anions along the proximal tubule but predominately
      in S2 segment. The relative contribution of both transporters depends on their
      relative expression levels and may possibly be affected by the activity of NaDC3
      in RPT.

PMID- 16815244
TI  - Investigating molecular recognition and biological function at interfaces using
      piscidins, antimicrobial peptides from fish.
AB  - We studied amidated and non-amidated piscidins 1 and 3, amphipathic cationic
      antimicrobial peptides from fish, to characterize functional and structural
      similarities and differences between these peptides and better understand the
      structural motifs involved in biological activity and functional diversity among
      amidated and non-amidated isoforms. Antimicrobial and hemolytic assays were
      carried out to assess their potency and toxicity, respectively. Site-specific
      high-resolution solid-state NMR orientational restraints were obtained from (15)N
      labeled amidated and non-amidated piscidins 1 and 3 in the presence of hydrated
      oriented lipid bilayers. Solid-state NMR and circular dichroism results indicate
      that the peptides are alpha-helical and oriented parallel to the membrane
      surface. This orientation was expected since peptide-lipid interactions are
      enhanced at the water-bilayer interface for amphipathic cationic antimicrobial
      peptides. (15)N solid-state NMR performed on oriented samples demonstrate that
      piscidin experiences fast, large amplitude backbone motions around an axis
      parallel to the bilayer normal. Under the conditions tested here, piscidin 1 was
      confirmed to be more antimicrobially potent than piscidin 3 and antimicrobial
      activity was not affected by amidation. In light of functional and structural
      similarities between piscidins 1 and 3, we propose that their topology and fast
      dynamics are related to their mechanism of action.

PMID- 16815245
TI  - Intravitreal bevacizumab for the management of choroidal neovascularization in
      age-related macular degeneration.
AB  - PURPOSE: To investigate the efficacy and safety of intravitreal bevacizumab for
      managing choroidal neovascularization (CNV) due to age-related macular
      degeneration (AMD). DESIGN: Prospective interventional case series. METHODS:
      Seventeen eyes of 17 patients with subfoveal CNV due to AMD participated in this
      study at the American University of Beirut Ophthalmology Clinics. All patients
      had failed, refused, or were not eligible for photodynamic therapy. All eyes
      received a baseline eye examination, which included best-corrected visual acuity
      (BCVA), dilated fundus examination, ocular coherence tomography (OCT) imaging,
      and fluorescein angiography. An intravitreal injection of bevacizumab (2.5 mg/0.1
      ml) was given at baseline and followed by two additional injections at four-week
      intervals. BCVA, OCT, and fluorescein angiography were repeated four weeks after
      each injection. Main outcome measures were improvement in BCVA and central
      retinal thickness (CRT). RESULTS: Mean baseline BCVA was 20/252 (median 20/200),
      and baseline CRT was 362 microm (median 350 microm). Improvement in VA and CRT
      occurred by the fourth week. At 12 weeks, mean BCVA was 20/76 (P < .001) and
      median BCVA was 20/50 (P < .001). Both mean and median CRT decreased to 211
      microm (P < .001). Thirteen (76%) of 17 eyes had total resolution of subretinal
      fluid, and four eyes (24%) had BCVA better than 20/50. No systemic or ocular side
      effects were noted at any time. CONCLUSION: Eyes with CNV due to AMD treated with
      intravitreal bevacizumab had marked anatomic and visual improvement. Further
      studies are necessary to confirm the long-term efficacy and safety of this
      treatment.

PMID- 16815246
TI  - Photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide in
      the treatment of neovascular age-related macular degeneration.
AB  - PURPOSE: To examine the efficacy of photodynamic therapy (PDT) with verteporfin
      and intravitreal triamcinolone acetonide in the treatment of neovascular age
      related macular degeneration (AMD). DESIGN: Retrospective, interventional case
      series. METHODS: Sixty eyes of 56 patients with neovascular AMD were treated with
      PDT with verteporfin followed by an intravitreal injection of 4 mg triamcinolone
      acetonide. The main outcome measures were visual acuity (VA), retreatment
      frequency with PDT (and triamcinolone), and frequency of side effects. RESULTS:
      Mean follow-up was 15.9 months (range 12 to 30 months, median 15 months). Twenty
      three (38.3%) of 60 eyes had a stable result at 12 months' follow-up (that is,
      loss/gain <three lines) and 34 (56.7%) of 60 had a loss of 3 lines or more. Three
      patients (5%) had an improvement of 3 lines or more. Lesion type, patient age,
      and lesion size had no influence on the outcome, but baseline VA had a
      statistically significant effect (P = .006). The median number of PDT
      intravitreal triamcinolone acetonide treatments was one. One-third (20 of 60) of
      all eyes had an increase in intraocular pressure (IOP) that required therapy.
      There were no cases of endophthalmitis, but 13 patients (21.6%) developed severe
      cataract that required surgery. CONCLUSIONS: The combination of PDT and
      intravitreal triamcinolone acetonide requires careful consideration as a
      treatment option for neovascular AMD. In our case series, this treatment
      combination did not prevent a considerable decrease in VA. The main benefit of
      this combination treatment was a low number of verteporfin treatments. Baseline
      VA was the main predictor of the final outcome.

PMID- 16815248
TI  - Functional outcome and patient satisfaction after Artisan phakic intraocular lens
      implantation for the correction of myopia.
AB  - PURPOSE: To determine patient satisfaction after Artisan phakic intraocular lens
      (PIOL) implantation to correct myopia. DESIGN: Non-comparative prospective case
      series. METHODS: One hundred twenty eyes of 60 patients who had undergone Artisan
      PIOL implantation to correct myopia were analyzed. A validated questionnaire that
      consisted of 66 satisfaction items were self-administered by patients 12 months
      after surgery. Clinical parameters (PIOL decentration, the difference between
      pupil size and PIOL optical zone, and optical aberrations) were measured. Main
      outcome measures of satisfaction scale scores (global satisfaction, quality of
      uncorrected and corrected vision, night vision, glare, day and night driving)
      were analyzed. Correlations with clinical parameters were obtained. RESULTS:
      After surgery, 98.3% of patients were satisfied, and 73.3% of patients considered
      their night vision to be the same or better; 44.1% of patients reported more
      bothersome glare. The night vision score correlated with spheric aberration (r = 
      0.303; P = .020). The glare score correlated with the difference between scotopic
      pupil size and PIOL optical zone (r = -0.280; P = .030) and vertical coma (r = 
      0.337; P = .009). The night driving score correlated with postoperative spheric
      equivalent (r = 0.375; P = .009), total root mean square aberrations (r = -0.337;
      P = .017), higher order root mean square aberrations (r = -0.313; P = .027), and
      vertical coma (r = -0.297; P = .036). CONCLUSION: Overall satisfaction after
      Artisan PIOL implantation for myopia is excellent. The quality of night vision
      and night driving were related to scotopic pupil size, individual higher order
      aberrations, and residual refractive error.

PMID- 16815247
TI  - Autologous translocation of the choroid and retinal pigment epithelium in age
      related macular degeneration.
AB  - PURPOSE: To evaluate the autologous translocation of peripheral choroid and
      retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related
      macular degeneration (AMD). DESIGN: Prospective nonrandomized study. METHODS: All
      patients had visual loss due to AMD (n = 5 classic membranes, n = 14 occult, n =
      2 mixed, n = 16 pigment epithelial detachment (PED), n = 5 subretinal hemorrhage,
      n = 3 geographic atrophy). After extraction of the neovascular complex, an
      autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid
      was translocated from the midperiphery to the macula. RESULTS: Preoperative
      distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4
      logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32
      Snellen equivalent). Revision surgery was required in 22 eyes as a result of
      proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or
      vitreous hemorrhage. In eight patients, the patch was renewed. At six months,
      distant visual acuity ranged from light perception to 20/50 (increase of 15
      letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual
      outcome was unrelated to the type of AMD. Vascularization of the transplant was
      visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most
      patients, autofluorescence of the pigment epithelium was coincident with
      revascularization of the graft. Fixation on the patch was positively related to
      visual acuity. CONCLUSIONS: Autologous translocation of a full-thickness
      transplant of choroid and RPE usually results in a vascularized and functioning
      graft. Vascularization was even achieved in patients with geographic atrophy.
      Fixation stability and microperimetry before the patch translocation may be
      helpful in selecting patients who will profit from surgery.

PMID- 16815249
TI  - Correlation between hemifield visual field damage and corresponding parapapillary
      atrophy in normal-tension glaucoma.
AB  - PURPOSE: To evaluate the correlation between the superior or inferior half area
      of parapapillary atrophy (PPA) and the corresponding hemifield visual field
      damage (VFD) in normal-tension glaucoma. DESIGN: Cross-sectional study. METHODS:
      patients: One hundred nine eyes of 109 consecutive patients with normal-tension
      glaucoma. observation procedures: Topography parameters of the optic nerve head
      and PPA (zone beta) area were obtained with the Heidelberg Retina Tomograph
      (HRT), and VFD was evaluated with the 30 to 2 program of Humphrey Field Analyzer.
      The HRT parameters and PPA area were determined separately in superior and
      inferior half regions. main outcome measures: Partial correlation coefficients of
      the superior and inferior areas of PPA with refractive error, axial length, HRT
      parameters, and corresponding hemifield VFD. RESULTS: In simple correlation
      analyses, significant correlation was found between the inferior PPA area and the
      superior hemifield VFD (Spearman rank correlation coefficient; Rs = -0.32; P <
      .001) but not between the superior PPA area and the inferior hemifield VFD (Rs =
      0.05; P = .6). Age, refractive error, axial length, and height variation contour
      were associated significantly with the total, superior, and inferior areas of
      PPA, respectively (P < .01). Multiple regression analyses showed that the
      superior PPA area was associated significantly with only axial length (P < .001),
      and the inferior PPA area was associated significantly with the axial length and
      the superior hemifield VFD (P < .001). CONCLUSIONS: In patients with normal
      tension glaucoma, only the inferior half area of PPA correlated significantly
      with glaucomatous VFD. Axial length and myopia were associated with both the
      superior and inferior half areas of PPA.

PMID- 16815250
TI  - Retinopathy of prematurity: two distinct mechanisms that underlie zone 1 and zone
      2 disease.
AB  - PURPOSE: In its most severe form, retinopathy of prematurity (ROP) is located in
      posterior retina and affects the smallest, most premature infants. We hypothesize
      that, depending on whether vasculogenesis (de novo formation of new vessels by
      transformation of vascular precursor cells (VPCs)) or angiogenesis (budding from
      existing vessels) is perturbed, it results in significant differences in clinical
      presentation and therapeutic outcome observed in zone 1 vs zone 2 ROP. DESIGN:
      The study is a retrospective analysis of the difference in outcome between zones
      1 and 2 ROP after cryotherapy and laser therapy. METHODS: A review of the
      clinical presentation of zones 1 and 2 ROP that correlate this with the
      topography of formation of human retinal vasculature through vasculogenesis and
      angiogenesis. RESULTS: Population data on susceptible infants, and outcome
      statistics of clinical trials are given. Digital images show a correlation
      between ROP in zone 1 with the region of the retina vascularized through
      vasculogenesis. CONCLUSION: Zone 1 ROP is correlated with vessel development by
      vasculogenesis, relative insensitivity to laser/cryotherapy and poorer anatomic
      and visual outcomes. This suggests that, if the vasculogenic process is
      perturbed, it results in a distinct clinical presentation, poorer response to
      therapy, and poorer visual outcome. When the current international classification
      was developed, knowledge of the processes of human retinal vascular development
      was incomplete. The work presented here provides a framework for the development
      of a modification to incorporate these ideas without sacrifice of the essential
      elements of the international classification of ROP.

PMID- 16815251
TI  - Association of blood pressure status with the optic disk structure in non
      glaucoma subjects: the Thessaloniki eye study.
AB  - PURPOSE: To study the association of blood pressure (BP) status on the optic disk
      structure as measured with the Heidelberg Retina Tomograph (HRT) in people
      without glaucoma. DESIGN: Cross-sectional population-based setting study.
      METHODS: Consecutive participants in the Thessaloniki Eye Study were included in
      this study. HRT images of the optic disk and BP measurements were taken.
      Hypertension was defined as a systolic BP (SBP) > or =140 mm Hg, diastolic BP
      (DBP) >/=90 mm Hg, or both. Subjects were classified in three groups by SBP and
      DBP. The Kruskal-Wallis test was used to compare the three groups with respect to
      the HRT parameters. Regression models adjusted for age, gender, height, disk
      size, intraocular pressure, cardiovascular disease, diabetes, and duration of
      antihypertensive treatment were used for each HRT parameter to compare values
      among the different groups. The P value was considered significant at <.05.
      RESULTS: A total of 232 subjects were included in the analysis. Rim area was
      significantly different among groups when DBP was considered as the criterion to
      classify subjects (P = .005). In regression models, cup area, and cup-to-disk
      (c/d) ratio were increased in subjects with normal DBP that was the result of
      treatment, as compared with both the high DBP and untreated normal DBP groups.
      CONCLUSIONS: In patients without glaucoma, the DBP <90 mm Hg that results from
      antihypertensive treatment is associated with increased cupping and decreased rim
      area of the optic disk. This information should be considered in research aiming
      to define the role of the BP status as an independent factor initiating optic
      disk changes and/or as a contributing factor to glaucoma damage.

PMID- 16815252
TI  - A comparison of autorefraction and subjective refraction with and without
      cycloplegia in primary school children.
AB  - PURPOSE: To evaluate the accuracy of autorefraction using three autorefractors
      comparing to subjective refraction in diagnosing refractive error in children.
      DESIGN: A cross-sectional study. METHODS: setting: Community based study. study
      population: 117 children sampled from primary schools. procedures: All subjects
      underwent autorefraction using three auto refractors and subjective refraction
      with and without cycloplegia. main outcome measures: Spherical power, cylindrical
      power, and spherical equivalence (SE). RESULTS: Without cycloplegia, the mean SE
      were significantly different for Retinomax K plus 2 (-1.55 diopters, SD 2.37
      diopters; 95% CI -1.98 to -1.12; P < .0001) and Canon RF10 (-1.11 diopters; SD
      2.61 diopters; 95% CI -1.59 to -0.64; P = .0023) compared with monocular
      subjective refraction (-0.80 diopters; SD 2.25 diopters; 95% CI -1.21 to -0.35).
      Mean SE was significantly different for Grand Seiko WR5100K (-0.79 diopters; SD
      2.40 diopters; 95% CI -1.23 to -0.35; P = .0002) compared with binocular
      subjective refraction (-0.62 diopters; SD 2.51 diopters; 95% CI -1.07 to -0.16).
      With cycloplegia, there was no significant difference in mean SE between
      refraction methods. Sensitivity and specificity results for the diagnosis of
      myopia: Without cycloplegia: Retinomax K plus 2 (sensitivity 1.0, specificity
      0.51); Canon RF10 (sensitivity 0.92, specificity 0.81); and Grand Seiko WR5100K
      (sensitivity 0.91, specificity 0.98). With cycloplegia: Retinomax K plus 2
      (sensitivity 0.97, specificity 0.99); Canon RF10 (sensitivity 0.97, specificity
      0.96); and Grand Seiko WR5100K (sensitivity 1.0, specificity 0.97). CONCLUSIONS:
      Under noncycloplegic conditions, all three autorefractors have a tendency towards
      minus over correction in children resulting in over diagnosis of myopia. However
      autorefractors were accurate under cycloplegic conditions.

PMID- 16815253
TI  - Occult thyroid eye disease in patients with unexplained ocular misalignment
      identified by standardized orbital echography.
AB  - PURPOSE: To describe the clinical presentation, orbital echography (OE) findings,
      and neuroimaging results of patients with chronic unexplained ocular
      misalignment, which includes patients with clinically occult thyroid eye disease
      (TED) that is identifiable through a characteristic OE appearance. DESIGN:
      Retrospective observational case series. METHODS: Seventy-eight patients with
      chronic ocular misalignment suspected of TED because of a history of systemic
      thyroid disease, proptosis, dysmotility, positive forced ductions, or eyelid
      retraction or lag were categorized as TED positive, negative, and indeterminate
      with the use of standardized OE. Demographic, clinical, OE, computed tomography,
      and magnetic resonance imaging information was collected. Analyses determined the
      prevalence of TED and differences between TED positive, negative, and
      indeterminate groups. RESULTS: Fifty-five percent of the findings were suspicious
      for and most consistent with TED (TED positive); 26% of the findings were TED
      negative, and 19% of the findings were TED indeterminate. Of 30 patients with
      newly diagnosed TED by OE, 70% had no lid retraction, and 20% had no other
      findings of TED. The inferior rectus followed by the superior rectus/levator
      complex, medial rectus, and lateral rectus muscles were the most frequently
      involved muscles. Neuroimaging that was performed in only 26 of 78 patients (33%)
      did not appear to yield additional diagnostic information. CONCLUSION: TED is a
      potential cause of chronic unexplained ocular misalignment in a substantial
      proportion of patients. These patients frequently present in an occult fashion
      without other clinical findings that are typical of TED. In these patients, a
      diagnosis of TED by OE can reduce further costly evaluation. OE appears to have
      significant clinical usefulness in the diagnosis of TED in patients with
      unexplained ocular misalignment.

PMID- 16815254
TI  - The evaluation of light sensitivity in benign essential blepharospasm.
AB  - PURPOSE: To test light sensitivity thresholds rigorously in patients with benign
      essential blepharospasm (BEB) compared with patients who have known light
      sensitivity (migraineurs) and to normal control subjects. DESIGN: Prospective,
      observational, case control study. METHODS: We recruited a total of 87 subjects
      into each of three groups: BEB, migraine, and normal control subjects. A modified
      slit-lamp chin rest, heat shield, light meter, and halogen light that was
      modulated by a rheostat were used to measure light sensitivity thresholds.
      Participants were tested without spectacles, with gray-tinted spectacles, and
      with FL-41-tinted spectacles. RESULTS: Light discomfort thresholds for subjects
      with BEB were significantly lower compared with normal control subjects (P < or =
      .009) and similar to the migraine group. Both gray and FL-41-tinted lenses
      improved light sensitivity thresholds in all groups (P < or = .0005). There was
      no observed difference in the improvement in light sensitivity when the gray and
      FL-41-tinted lenses were compared. CONCLUSION: Patients with BEB are considerably
      more sensitive to light than control subjects and as sensitive to light as
      patients with migraine. Physicians who care for patients with BEB should consider
      using tinted lenses to help ameliorate symptoms.

PMID- 16815255
TI  - Diabetes-associated retinal nerve fiber damage evaluated with scanning laser
      polarimetry.
AB  - PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness in patients with
      diabetes mellitus compared with age-matched normal control subjects, to assess
      the correlation between the RNFL thickness and the severity of retinopathy, and
      to investigate whether diabetes mellitus is a potential source of abnormal
      results in glaucoma screening or evaluation with scanning laser polarimetry
      (SLP). DESIGN: Cross-sectional analysis of normal and diabetic eyes. METHODS:
      setting: Institutional clinical study. patients: One hundred twenty-eight
      subjects with type 2 diabetes mellitus and 50 age-matched normal control subjects
      without glaucoma or glaucoma-suspect. All patients underwent imaging with SLP and
      repeatable automated perimetry. Subjects with diabetes mellitus were classified
      into four stages on the basis of the severity of retinopathy that was assessed by
      dilated funduscopic examination, high-quality fundus color photography, and
      fluorescein angiography. MAIN OUTCOME MEASURES: The SLP (GDx VCC software,
      version 5.5.0) parameters. RESULTS: The RNFL thickness in patients with diabetes
      mellitus was reduced significantly compared with age-matched normal control eyes
      (P < .01). Moreover, all RNFL thickness parameters of the GDx VCC software
      decreased significantly as an exacerbation of diabetic retinopathy (P = .0019, P
      = .0045, P = .0010 for temporal-superior-nasal-inferior-temporal (TSNIT) average,
      superior average, inferior average, respectively). The nerve fiber indicator also
      increased significantly (P < .0001), despite an absence of glaucomatous optic
      nerve damages. CONCLUSION: The RNFL thickness in type 2 diabetes mellitus, which
      was measured by GDx VCC software, significantly decreased with the severity of
      diabetic retinopathy. The presence of diabetes mellitus can be a source of false
      positive results and overestimation of glaucomatous optic neuropathy when eyes
      are screened with GDx VCC software.

PMID- 16815256
TI  - Expression of VEGF and PEDF in choroidal neovascular membranes following
      verteporfin photodynamic therapy.
AB  - PURPOSE: To examine the impact of photodynamic therapy (PDT) on pigment
      epithelium derived factor (PEDF) expression in human choroidal neovascularization
      (CNV) membranes with regard to vascular endothelial growth factor (VEGF)
      expression. DESIGN: Interventional case series. METHODS: Retrospective review of
      interventional case series of 42 patients (42 eyes) who underwent removal of CNV.
      CNV was secondary to age-related macular degeneration (AMD) in all cases. Fifteen
      patients were treated with PDT, 3 to 246 days before surgery. CNV were stained
      for CD34, CD105, cytokeratin 18, VEGF, and PEDF. Twenty-seven CNV without
      previous treatment were used as control. RESULTS: Specimens without pretreatment
      disclosed varying degrees of vascularization, VEGF, and PEDF expression by
      different cells. Specimens treated by PDT, three days previously showed mostly
      occluded vessels lined with damaged endothelial cells (EC). In contrast,
      specimens excised at later time points after PDT were highly vascularized with
      healthy EC. This chronology was associated with an impressive VEGF
      immunoreactivity increased considerably in retinal pigment epithelial cells as
      well as significantly reduced PEDF expression in EC and stroma. CONCLUSIONS: PDT
      induces a selective vascular damage in CNV. The effectiveness of PDT, however,
      seems to be jeopardized by a rebound effect initiated by an enhanced VEGF and
      reduced PEDF expression in CNV.

PMID- 16815257
TI  - Apolipoprotein E gene polymorphisms are not associated with diabetic retinopathy:
      the atherosclerosis risk in communities study.
AB  - PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated
      with dyslipidemia and cardiovascular disease. This study examines the association
      of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross
      sectional study. METHODS: We studied 1,398 people aged 49 to 73 years with
      diabetes selected from four United States communities. We performed retinal
      photography on one randomly selected eye and graded for the presence and severity
      of diabetic retinopathy using a modification of the Early Treatment Diabetic
      Retinopathy Study scale. We performed genotyping of common polymorphic APOE
      alleles using polymerase chain reaction on genomic DNA from venous blood
      leukocytes. RESULTS: The prevalence of diabetic retinopathy and hard exudates was
      15.0% and 5.3% in Caucasians (n = 935), and 24.6% and 9.7% in African-Americans
      (n = 463), with type 2 diabetes. APOE gene polymorphisms were not associated with
      diabetic retinopathy in either Caucasians or African-Americans. In African
      Americans, the 2/4 genotype (n = 6) was associated with increased prevalence of
      hard exudates (odds ratio [OR] 4.10, 95% confidence interval [CI] 1.30 to 12.90),
      as was the 2/3 genotype (n = 9, OR 2.64, 95% CI 1.01 to 6.95). No association
      between APOE genotypes and hard exudates was found in Caucasians. CONCLUSIONS:
      These data suggest that APOE gene polymorphisms are not associated with diabetic
      retinopathy in either Caucasians or African-Americans with type 2 diabetes.

PMID- 16815258
TI  - Correctable and non-correctable visual impairment in a population-based sample of
      12-year-old Australian children.
AB  - PURPOSE: To document the prevalence of correctable and non-correctable visual
      impairment in a representative sample of Australian children, predominantly age
      12 years. DESIGN: Population-based cross-sectional study. METHODS: Logarithm of
      the minimum angle of resolution (logMAR) visual acuity was measured in both eyes
      unaided, with spectacles if worn, and after subjective refraction if required, in
      2353 children, examined during 2004 to 2005. Cycloplegic autorefraction (using
      cyclopentolate) and dilated fundus examination were performed. Using a cut-off of
      0.3 logMAR units (<20/40), presenting visual impairment was defined using unaided
      visual acuity if spectacles were not worn or with usual correction if spectacles
      were worn. Impairment not eliminated by refraction was considered non
      correctable; any difference between this and presenting impairment was defined as
      correctable impairment. Myopia was defined as spherical equivalent refraction
      (SER) < or =-0.50 diopters (D), hyperopia as SER > or =+2.0 diopters,
      anisometropia as SER difference > or =1.00 diopters, and astigmatism as cylinder
      > or =1.0 diopters. Amblyopia was defined as corrected visual acuity <0.3 logMAR
      not attributable to an underlying structural eye or visual pathway abnormality.
      RESULTS: Visual impairment was found in the worse eye of 117 children (5.0%) and
      comprised correctable (82%) and non-correctable impairment (18%). Correctable
      impairment was due to myopia in 67 (69.8%), hyperopia in 11 (11.5%) and
      astigmatism in 32 subjects (33.3%). Causes of non-correctable impairment were:
      amblyopia 66.7%, congenital glaucoma 9.5%, optic nerve hypoplasia 9.5%,
      congenital nystagmus 4.8%, and cortical blindness 4.8%. CONCLUSIONS: Visual
      impairment had a relatively low prevalence in this older childhood population, a
      large proportion of which was correctable by refraction alone.

PMID- 16815259
TI  - Evaluation of the effect on outcomes of the route of administration of
      corticosteroids in acute Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To compare the effect on outcomes of the route of administration of
      corticosteroids in acute Vogt-Koyanagi-Harada disease. DESIGN: Retrospective
      comparative interventional case series. METHODS:  SETTINGS: Nine international
      uveitis specialty clinics. STUDY POPULATION: Forty-eight patients presenting over
      a three-year period to a study center with acute Vogt-Koyanagi-Harada disease.
      INTERVENTION: Initial treatment with corticosteroid either orally (Oral only
      group) or intravenously followed by an oral taper (IV+Oral group). MAIN OUTCOME
      MEASURES: Change in visual acuity with treatment; development of ocular
      complications, including visually significant cataract, choroidal
      neovascularization, subretinal fibrosis, fundus pigment migration, nummular
      hypopigmented lesions, and diffuse fundus depigmentation; use of
      immunosuppressive therapy. RESULTS: The Oral only group comprised 15 patients
      (31%) and the IV+Oral group 33 patients (69%). Median follow-up was 15 months.
      There was no difference in duration of follow-up between groups (P = .234). There
      was no difference in the change in visual acuity between groups, adjusting for
      initial visual acuity (P = .402). There were no differences in the rates of
      development of visually significant cataract, fundus pigmentary changes, or in
      the rate of use of subsequent immunosuppressive therapy between treatment groups.
      No patients developed choroidal neovascularization or subretinal fibrosis over
      the study period. CONCLUSIONS: Route of administration of corticosteroid had no
      detectable effect on change in visual acuity nor on the development of visually
      significant complications over the study period. Prospective trials are necessary
      to address speed of resolution and definitively answer outcome questions.

PMID- 16815260
TI  - Validation and repeatability of a short questionnaire for dry eye syndrome.
AB  - PURPOSE: To clinically validate and ascertain the repeatability of a short
      questionnaire for dry eye syndrome (DES), consisting of two questions pertaining
      to symptoms (dryness and irritation) and one question regarding previous history
      of clinically diagnosed DES. DESIGN: Clinical validation study with repeated
      assessments. METHODS: A short questionnaire for DES was administered to
      participants of two large cohort studies, the Women's Health Study (WHS) and the
      Physicians' Health Study (PHS). A supplementary questionnaire comprising 16
      questions pertaining to symptoms was mailed to a subset of 450 WHS and 240 PHS
      participants, selected so that a third of these subjects had DES based on their
      response to the short questionnaire. Repeatability of the dryness and irritation
      symptom questions was ascertained using intraclass correlation coefficient (ICC).
      Standardized ophthalmologic examination was performed on 53 subjects. Sensitivity
      and specificity of the short questionnaire was determined using a combination of
      clinical tests to define clinical DES. RESULTS: An ICC of 0.75 for dryness and
      0.65 for irritation was found between subsequent measurements. Participants'
      responses to the dryness and irritation questions were highly correlated (r =
      0.75) with a score derived from responses to the longer 16-symptom questionnaire.
      The short questionnaire for DES had a sensitivity of 77% and specificity of 83%
      when cutoff point for clinical DES was Schirmer 1 value </=10 mm or tear breakup
      time <10 seconds. CONCLUSION: The short questionnaire for DES is a sensitive and
      repeatable tool that is easy to administer in large epidemiologic research
      studies as well as clinical research.

PMID- 16815261
TI  - Relationship between anisometropia, patient age, and the development of
      amblyopia.
AB  - PURPOSE: Previous studies evaluating the effect of anisometropia on amblyopia
      development have been biased because subject selection occurred as a result of
      decreased acuity. Photoscreening identifies anisometropic children in a manner
      that is not biased by acuity, and allows an opportunity to evaluate how patient
      age influences the prevalence and depth of amblyopia. DESIGN: Retrospective
      observational study of preschool children with anisometropia. METHODS: A
      statewide preschool photoscreening program screened 119,311 children and
      identified 792 with anisometropia >1.0 diopters. We correlated age with visual
      acuity and amblyopia depth. Results were compared with 562 strabismic children
      similarly identified. RESULTS: Only 14% (six of 44) of anisometropic children
      aged 1 year or younger had amblyopia. Amblyopia was detected in 40% (32 of 80) of
      2-year-olds, 65% (119 of 182) of 3-year-olds, and 76% of 5-year-olds. Amblyopia
      depth also increased with age. Moderate amblyopia prevalence was 2% (ages 0 to
      1), 17% (age 2), and rose steadily to 45% (ages 6 to 7). Severe amblyopia was
      rare for children aged 0 to 3, 9% at age 4, and 14% at age 5. Children with
      strabismus had a relatively stable prevalence (30% ages 0 to 2; 42% ages 3 to 4;
      and 44% ages 5 to 7) and depth of amblyopia. CONCLUSIONS: Younger children with
      anisometropia have a lower prevalence and depth of amblyopia than older children.
      By age 3, when most children undergo traditional screening, amblyopia has usually
      already developed. New vision screening technologies that allow early detection
      of anisometropia provide ophthalmologists an opportunity to intervene early,
      perhaps retarding or even preventing the development of amblyopia.

PMID- 16815262
TI  - Intravitreal avastin: the low cost alternative to lucentis?

PMID- 16815263
TI  - Association of blood pressure status with the optic disk structure.

PMID- 16815264
TI  - The contact lens/fusarium "outbreak".

PMID- 16815265
TI  - Pathogenesis of graves ophthalmopathy: implications for prediction, prevention,
      and treatment.
AB  - PURPOSE: To review current concepts regarding the pathogenesis of Graves
      ophthalmopathy (GO). We have presented this information in the context of
      potential target sites for novel disease therapies. DESIGN: Review of recent
      literature. METHODS: Synthesis of recent literature. RESULTS: Enlargement of the
      extraocular muscle bodies and expansion of the orbital fatty connective tissues
      is apparent in patients with GO. These changes result from abnormal hyaluronic
      acid accumulation and edema within these tissues and expanded volume of the
      orbital adipose tissues. Recent studies have suggested that the increase in
      orbital fat volume is caused by stimulation of adipogenesis within these tissues.
      The orbital fibroblast appears to be the major target cell of the autoimmune
      process in GO. A subset of these cells is capable of producing hyaluronic acid
      and differentiating into mature adipocytes, given appropriate stimulation. In
      addition, orbital fibroblasts from patients with GO have been shown to display
      immunoregulatory molecules and to express both thyrotropin receptors (TSHRs) and
      insulin-like growth factor 1 receptors (IGF-1Rs). Increased TSHR expression in
      the GO orbit appears to be the result of stimulated adipocyte differentiation.
      The activation of IGF-1R on orbital fibroblasts by immunoglobulins from GO
      patients results in increased production of both hyaluronic acid and molecules
      that stimulate the infiltration of activated T cells into areas of inflammation.
      CONCLUSIONS: Potential targets for novel therapeutic agents to be used in GO
      include blocking T-cell costimulation, depleting B cells, inhibiting cytokine
      action, targeting the IGF-1R or the TSHR, and preventing connective tissue
      remodeling.

PMID- 16815266
TI  - Fungal keratitis associated with non-therapeutic soft contact lenses.
AB  - PURPOSE: To report an increase in culture-positive contact lens-associated fungal
      keratitis. DESIGN: Retrospective, cross-sectional laboratory study. METHODS:
      Microbiology records of culture-positive fungal keratitis cases from January 2004
      to December 2005 were reviewed. RESULTS: Recovery of fungal pathogens among
      wearers of contact lenses increased from 26.7% (eight of 30) to 50% (18 of 36) of
      isolates in 2005. Fusarium species (66 of 122, 54.1%) were the most frequent
      fungal pathogens. Soft contact lens wear among the Fusarium cases more than
      doubled (seven of 30, 23.3%, vs 17 of 36, 47.7%, P = .046) from 2004 to 2005.
      CONCLUSIONS: Contact lens wear may be a risk factor in fungal keratitis.

PMID- 16815267
TI  - Regression of iris neovascularization after intravitreal injection of bevacizumab
      in patients with proliferative diabetic retinopathy.
AB  - PURPOSE: To assess the short-term safety and efficacy of intravitreal injection
      of bevacizumab for iris neovascularization (INV). DESIGN: Noncomparative,
      interventional case series. METHODS: Intravitreal bevacizumab was injected in
      seven eyes of five patients with INV that was associated with proliferative
      diabetic retinopathy (PDR). The main outcome measurements were visual acuity,
      intraocular pressure (IOP), and regression of INV by fluorescein angiography
      before and one week, one month, and two months after injection. RESULTS:
      Regression of INV was confirmed in all eyes (100%) from one week after injection.
      Repeated injections stabilized the recurrence (two eyes; 29%) that was observed
      two months after the initial injection. The visual acuity remained stable or
      improved, and the intraocular pressure was controlled in six eyes (86%)
      throughout the follow-up period. No inflammation or complications were observed.
      CONCLUSIONS: Intravitreal injection of bevacizumab may be an effective and safe
      alternative for patients with INV that is refractory to conventional treatments.

PMID- 16815268
TI  - Intracameral bevacizumab for iris rubeosis.
AB  - PURPOSE: To determine whether intracameral bevacizumab decreases vascular leakage
      from iris rubeosis in patients with neovascular glaucoma. DESIGN: Interventional
      case series. METHODS: The study included six eyes of three patients with
      secondary neovascular glaucoma due to proliferative diabetic retinopathy (n = 2)
      or ischemic central retinal vein occlusion (n = 1). All patients received an
      intracameral injection of 1.0 mg bevacizumab. Morphologic changes and vascular
      leakage were investigated prospectively by iris fluorescein angiography. RESULTS:
      Decrease in leakage was detected as early as one day after injection. No
      inflammation was observed. No relapse was seen within the follow-up of four
      weeks. CONCLUSION: Intraocular injection of bevacizumab may provide an additional
      strategy for the treatment of iris rubeosis in neovascular glaucoma.

PMID- 16815269
TI  - Retinal pigment epithelial tears after pegaptanib injection for exudative age
      related macular degeneration.
AB  - PURPOSE: To report two cases of retinal pigment epithelium (RPE) tears following
      intravitreal pegaptanib injections for occult choroidal neovascularization.
      DESIGN: Noncomparative case series. METHODS: The charts of two patients with
      pigment epithelial tears after receiving intravitreal pegaptanib were reviewed.
      Approval from the institutional review board and informed consent were obtained
      before chart review. Fundus photos, intravenous fluorescein angiograms, and
      optical coherence tomography (OCT) were obtained before and after therapy
      confirmed the diagnosis. RESULTS: Two patients had turbid pigment epithelial
      detachments (PEDs) and occult choroidal neovascular membranes (CNVMs) treated
      with intravitreal pegaptanib. Both patients developed RPE tears weeks following
      one intravitreal pegaptanib injection. CONCLUSIONS: This report describes the
      development of RPE tears after intravitreal pegaptanib injection. Caution should
      be taken in cases of turbid pigment epithelial detachments in the monocular
      patient when treatment with intravitreal pegaptanib is entertained. Future
      studies should be performed to evaluate which subtypes of lesions are most
      susceptible to this devastating visual complication.

PMID- 16815270
TI  - Absence of histologic retinal toxicity of intravitreal bevacizumab in a rabbit
      model.
AB  - PURPOSE: To evaluate the retinal toxicity of intravitreal bevacizumab in an
      animal model. DESIGN: Animal study. METHODS: Bevacizumab was injected into the
      vitreous of one eye of each of eight Dutch-belted rabbits; the other eye served
      as a control. Four rabbits received a dose of 1.25 mg/0.05 ml of bevacizumab
      intravitreally into one eye, and the other four rabbits were injected with 2.5
      mg/0.1 ml of bevacizumab intravitreally into one eye. At one month, the rabbits
      were killed and both eyes enucleated. The eyes were fixed with paraformaldehyde
      2% and examined by light microscopy. RESULTS: In all injected and control eyes,
      there was mild vacuolization in the ganglion cell layer, and disruption of
      photoreceptor outer segments in both treated and control eyes, to the same
      degree, consistent with autolysis. The optic nerve, retina, and retinal pigment
      epithelium were otherwise normal by light microscopy with no evidence of
      toxicity. CONCLUSIONS: Intravitreal bevacizumab at doses of 1.25 mg and 2.5 mg
      showed no signs of retinal or optic nerve toxicity by light microscopy in this
      rabbit model.

PMID- 16815271
TI  - Evaluating central corneal thickness measurements with noncontact optical low
      coherence reflectometry and contact ultrasound pachymetry.
AB  - PURPOSE: To compare the central corneal thickness (CCT) measurements obtained
      with noncontact optical low-coherence reflectometry (OLCR) and ultrasound (US)
      pachymetry. DESIGN: Prospective, comparative observational study. METHODS: Three
      sequential ultrasonic measurements and a set of five OLCR scans of 52 eyes of 26
      healthy subjects were recorded. Noncontact measurement was repeated five minutes
      after anesthetic drop instillation. RESULTS: Mean CCT values for noncontact OLCR
      and US pachymetry were 544.03 microm and 548.66 microm, respectively, with mean
      SDs of 0.97 microm and 4.63 microm, respectively. Noncontact OLCR measured on
      average 4.64 microm less than US pachymetry (95% confidence interval -7.56 to 
      1.72; P = .003). The OLCR measured 1.68 microm less than US pachymetry in the
      thinner cornea group (< or =548.7 microm, n = 24) and 7.48 mum less in the
      thicker group (n = 25). This difference was statistically significant (P = .04).
      CONCLUSIONS: There was agreement between the two pachymetric measurements.
      Noncontact OLCR appeared to measure slightly smaller than US pachymetry.

PMID- 16815272
TI  - Inferior corneal decompensation following laser peripheral iridotomy in the
      superior iris.
AB  - PURPOSE: To describe a previously unreported clinical entity of inferior corneal
      decompensation occurring as a long-term complication of superior laser peripheral
      iridotomy. DESIGN: Retrospective, non-comparative observational case series.
      METHODS: Chart review of 14 subjects (16 eyes) with inferior corneal
      decompensation. RESULTS: All patients were Chinese, most were females (71.4%),
      and the mean age was 69.5 +/- 8.1 year. The mean interval from iridotomy to the
      onset of inferior corneal decompensation was 66.1 +/- 34.0 months. The most
      common indication for laser iridotomy was for prophylaxis, either in the fellow
      eye of acute angle closure (43.8%) or for occludable angles (12.5%). CONCLUSIONS:
      Corneal decompensation in the inferior part of the cornea at a site remote from
      the iridotomy is a rare but important complication of laser iridotomy. Because
      many of the laser iridotomies were performed prophylactically in eyes without
      glaucoma, patients may need to be warned of this risk.

PMID- 16815273
TI  - Optic disk size in chronic glaucoma: the Beijing eye study.
AB  - PURPOSE: To evaluate whether eyes with chronic glaucoma have a larger or smaller
      optic disk than normal eyes. DESIGN: Population-based, cross-sectional cohort
      study. METHODS: The study included 4439 subjects out of 5324 subjects invited to
      participate with an age of 40+ years. Color optic disk photographs (45 degrees )
      were morphometrically examined. RESULTS: After exclusion of aphakic eyes,
      pseudophakic eyes, and highly myopic eyes, data of 3989 subjects entered the
      statistical analysis. The mean optic disk area did not vary significantly (P >
      .05) between the nonglaucomatous group (2.61 +/- 0.50 mm(2)), eyes with
      glaucomatous appearance of the optic disk (2.69 +/- 0.63 mm(2)), eyes with
      glaucomatous optic disks and visual field defects (2.66 +/- 0.70 mm(2)), and eyes
      with elevated intraocular pressure (2.63 +/- 0.49 mm(2)). CONCLUSIONS: In adult
      Chinese, optic disk size may not markedly differ between normal eyes and eyes
      with chronic glaucoma.

PMID- 16815274
TI  - Optical coherence tomography in choroidal tuberculosis.
AB  - PURPOSE: To report the optical coherence tomographic (OCT) features in eyes with
      tuberculous choroidal granuloma. DESIGN: Interventional case series. METHODS:
      Nine eyes of nine patients with tuberculous granuloma of the choroid were studied
      using OCT scans. RESULTS: OCT scan through the lesions revealed a distinctive
      feature of attachment between the retinal pigment epithelial- choriocapillaris
      layer and the neurosensory retina over the granuloma ("contact" sign). This was
      associated with surrounding subretinal fluid and inflammatory infiltrate in the
      deeper retinal layers. CONCLUSIONS: OCT can be useful in the differentiating
      choroidal tuberculous granulomas from noninflammatory lesions with a similar
      clinical appearance.

PMID- 16815275
TI  - Delayed corneal epithelial wound healing after penetrating keratoplasty in
      individuals with lattice corneal dystrophy.
AB  - PURPOSE: To investigate whether corneal epithelial cells of individuals with
      lattice corneal dystrophy (LCD) possess an intrinsic defect. DESIGN:
      Retrospective case-control study. METHODS: The medical charts of nine individuals
      with LCD and those of 14 patients with keratoconus and 11 patients with corneal
      leukoma (controls), all of whom underwent penetrating keratoplasty (PKP) in one
      eye at Yamaguchi University Hospital between February 1998 and November 2001,
      were examined for the time for epithelial resurfacing after surgery. RESULTS: The
      time required for resurfacing of the corneal epithelium after PKP was
      significantly greater in LCD patients (8.56 +/- 4.95 days, mean +/- SD) than in
      patients with either keratoconus (1.71 +/- 0.91 days, P = .006) or corneal
      leukoma (3.00 +/- 1.95 days, P = .03). CONCLUSIONS: Corneal epithelial wound
      healing was delayed in LCD patients after PKP, suggesting that the
      keratoepithelin gene mutations responsible for this condition affect corneal
      epithelial cells.

PMID- 16815276
TI  - Corneal copper deposition associated with chronic lymphocytic leukemia.
AB  - PURPOSE: To report a case of corneal copper deposition associated with chronic
      lymphocytic leukemia (CLL). DESIGN: Case report. METHODS: A 65-year-old woman
      with a history of CLL was diagnosed with bilateral corneal opacification. Slit
      lamp examination revealed dense, central yellow-brown pigmentation of Descemet's
      membrane in each cornea. The presence of a bilateral pigmented deposition at the
      level of Descemet's membrane led to a presumptive clinical diagnosis of corneal
      copper deposition. RESULTS: Serologic investigations revealed a markedly elevated
      copper (hypercupremia) and IgG levels with a normal ceruloplasmin. Wilson's
      disease was excluded as a possible cause based on liver function tests and a
      liver biopsy. Thus, the patient was diagnosed with corneal copper deposition
      secondary to hypercupremia associated with CLL. CONCLUSIONS: Corneal copper
      deposition may be associated with systemic malignancy, most commonly
      myeloproliferative disorders, including CLL. Recognition of the characteristic
      clinical features associated with corneal copper deposition allows the clinician
      to confirm the diagnosis with appropriate serologic studies.

PMID- 16815277
TI  - Evaluation of macular changes before and after successful retinal detachment
      surgery using stratus-optical coherence tomography.
AB  - PURPOSE: To assess preoperative and postoperative infra-clinical macular changes
      in macula-off retinal detachment (RD) using third-generation optical coherence
      tomography (OCT3). DESIGN: Prospective observational cohort study. METHODS:
      Twenty-two nonconsecutive eyes of 22 patients with macula-off RD underwent best
      corrected visual acuity measurement and OCT3 scans through the fovea before and
      after successful surgery. The relationship between preoperative and postoperative
      OCT macular characteristics, postoperative infra-clinical foveal detachment, and
      final visual acuity (FVA) were assessed using Kruskal-Wallis multiple comparison
      test and Mann-Whitney U test, respectively. RESULTS: Preoperative cystic cavities
      in the inner nuclear layer of the detached retina, postoperative abnormal macular
      profile, and postoperative lack of the junction line between photoreceptor cell
      inner and outer segments on OCT3 were associated with a poorer FVA (P = .001, P =
      10(-4) and P = .015, respectively). In contrast, postoperative infra-clinical
      foveal detachment did not influence FVA (P = .88). CONCLUSIONS: Morphologic
      macular analysis using OCT3 provide some new insights to understand incomplete
      visual recovery after successful macula-off RD surgery.

PMID- 16815278
TI  - Effect of hospitalization on intraocular pressure in patients with high tension
      and normal tension glaucoma.
AB  - PURPOSE: To determine the effect of hospitalization on intraocular pressure (IOP)
      in glaucoma patients. DESIGN: Prospective case series. METHODS: IOP was measured
      on three consecutive days in 26 high-tension (HTG) and 13 normal-tension (NTGwm)
      glaucoma patients under IOP-lowering treatment, and in 28 normal-tension glaucoma
      patients without IOP-lowering treatment (NTGnm), and change was compared by
      analysis of variance. RESULTS: IOP decreased significantly, but comparably, in
      the three groups and between right and left eyes, although, the relative change
      to IOP on day 1 was significantly less pronounced in the group without treatment
      on day 2 and 3 compared with the treated groups. CONCLUSIONS: Glaucoma patients
      showed a significant decrease in IOP during hospitalization. Although this
      decrease was more pronounced among the treated patients, it was also present in
      nontreated patients. Consequently, other factors than improved compliance during
      hospitalization must play a role in this phenomenon.

PMID- 16815279
TI  - Pilot study on in vivo evaluation of retinal vascular maturity in newborn infants
      in the context of retinopathy of prematurity.
AB  - PURPOSE: To study the extent of retinal vascularization at birth. DESIGN:
      Prospective masked observational case series. METHODS: One hundred ten neonates,
      at different weeks of gestation and birth weights (BWs), had dilated fundus
      evaluation for zone of retinal vascularization by a masked observer. Maternal and
      neonatal factors were ascertained by a masked pediatrician. RESULTS: Irrespective
      of risk factors, eight of nine babies who were born at <30 weeks of gestation and
      at <1500 g BW had immature retina. Those babies who were born at >34 weeks of
      gestational age and at >1700 g BW had mature retina. Babies who were born between
      31 to 34 weeks of gestation and at 1501 to 1700 g BW had variable extent of
      retinal vascularization at birth. Vascularization was affected by maternal anemia
      and the need for oxygen for >48 hours. CONCLUSION: There exists considerable
      variability in the extent of retinal vascularization in infants who are born
      between 31 to 34 weeks of gestation. Modifiable maternal and fetal factors could
      influence extent of this vascularization birth.

PMID- 16815280
TI  - Ocular methicillin-resistant Staphylococcus aureus infections in a newborn
      intensive care cohort.
AB  - PURPOSE: To examine the occurrence and outcome of methicillin-resistant
      Staphylococcus aureus ophthalmologic infections in a newborn intensive care unit
      cohort. DESIGN: Noninterventional case series. METHODS: Over a 13-month period,
      29 neonates were colonized with methicillin-resistant S. aureus in a newborn
      intensive care unit outbreak. Patients were followed prospectively during the
      course of colonization and infection. The frequency and type of ophthalmologic
      infection was recorded, and patients were treated according to clinical need.
      RESULTS: Eleven of these patients were found to have purulent conjunctivitis. No
      serious ocular disease ensued in any of these. Spontaneous resolution occurred in
      some patients, while others improved after either topical or systemic antibiotic
      treatment. CONCLUSION: Despite invasive infection caused by methicillin-resistant
      S. aureus, serious ophthalmologic infection was not found.

PMID- 16815281
TI  - Effects of topical antiglaucoma application on conjunctival impression cytology
      specimens.
AB  - PURPOSE: To evaluate the changes in conjunctival impression cytology specimens
      from patients receiving various topical antiglaucoma medications. DESIGN: Cross
      sectional comparative study. METHODS: Impression cytology specimens were obtained
      from the eyes taking no topical medication (n = 20) and from the eyes taking
      various antiglaucoma medications (timolol n = 34; latanoprost n = 40; dorzolamide
      n = 32; timolol + latanoprost n = 30; timolol + dorzolamide n = 34). Specimens
      were graded on a scale of zero to three according to Nelson's method. RESULTS:
      Cytology scores were significantly higher in the medication group than the
      control group. Mean cytology scores of the control, timolol, latanoprost,
      dorzolamide, timolol + latanoprost, and timolol + dorzolamide group were 0.20,
      1.62, 2.00, 1.75, 2.13, and 2.44, respectively. Among the medication groups,
      cytology scores were significantly lower in the monotherapy group than the fixed
      combination therapy group. CONCLUSIONS: Various topical antiglaucoma medications
      induce a significant degree of squamous metaplasia. Conjunctival surface could be
      altered after the long-term use of antiglaucoma medication.

PMID- 16815282
TI  - Bull's-eye maculopathy in an infant with Leigh disease.
AB  - PURPOSE: To report a bull's-eye maculopathy-like fundus abnormality in an infant
      with Leigh disease. DESIGN: Observational case report. METHODS: We reviewed the
      medical, ophthalmic, and genetic records of an eight-month-old boy who presented
      with hypotonia and bilaterally decreased vision. RESULTS: The ophthalmic
      examination revealed poor fixation, marked hyperopia, attenuated retinal vessels,
      and bull's-eye maculopathy. A white blood cell mitochondrial DNA analysis
      demonstrated a T to G mutation at position 8993 in the mitochondrial ATPase 6
      gene. A skeletal muscle biopsy was homoplasmic for this mutation, consistent with
      a severe mitochondrial disorder. CONCLUSION: Leigh disease should be included in
      the differential diagnosis of patients presenting with neurologic deficits and a
      bull's-eye maculopathy.

PMID- 16815283
TI  - Periorbital zygomycosis (mucormycosis) treated with posaconazole.
AB  - PURPOSE: To report on the successful treatment of periorbital zygomycosis
      (mucormycosis) with posaconazole, a broad-spectrum oral antifungal available for
      compassionate use. DESIGN: Interventional case report. METHODS: Review of a
      medical record. RESULTS: A 22-year-old male undergoing induction chemotherapy for
      acute lymphoblastic leukemia presented with periorbital cellulitis attributable
      to Rhizopus. The patient was initially treated with liposomal amphotericin B,
      surgical debridement, and reversal of immune compromise. The patient was switched
      to posaconazole because of amphotericin side effects and lack of improvement. He
      took posaconazole for five months while undergoing additional cycles of
      chemotherapy. Despite recurrent profound neutropenia, the periorbital infection
      resolved, he tolerated reconstructive procedures, and he did not develop orbital
      invasion. His Rhizopus isolate was highly susceptible to posaconazole in vitro.
      CONCLUSIONS: Drug toxicities can limit the use of amphotericin in some patients
      with zygomycosis. Posaconazole shows promise as an alternative antifungal agent
      in the treatment of periorbital zygomycosis.

PMID- 16815284
TI  - Use of fibrin glue in fixation of amniotic membranes in sterile corneal
      ulceration.
AB  - PURPOSE: To describe a method of fibrin glue fixation of single or multilayered
      amniotic membranes in sterile corneal ulceration. DESIGN: A modified
      microsurgical procedure. METHODS: The corneal ulcer is cleaned and the components
      of fibrin glue are applied separately. Amniotic membranes are rotated through the
      fibrinogen component and subsequently into the site of the ulceration where
      thrombin is already applied. An overlay membrane is sutured additionally on top.
      The results for one patient are illustrated as an example. RESULTS: The
      application technique prevents development of foam and leads to a thin fibrin
      film, which minimizes any irregularities of the fixed membranes and creates extra
      time to adjust the membranes' position. CONCLUSIONS: This method presents as an
      effective procedure for the treatment of sterile corneal ulceration and creates
      valuable time if any elective corneal graft procedure is required.

PMID- 16815285
TI  - Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis
      and cystoid macular edema.
AB  - PURPOSE: To investigate the global cytokine and chemokine expression pattern in
      the aqueous humor of uveitis patients and relate them to clinical features.
      DESIGN: Cross-sectional study. METHODS: In 31 aqueous humor samples from uveitis
      patients, the concentration of mediators was measured by a multiplex immunoassay.
      Eleven control samples were included. RESULTS: Uveitis samples had higher levels
      of interleukin-6, interleukin-8, soluble intercellular adhesion molecule, soluble
      vascular cell adhesion molecule (sVCAM), and interferon-inducible protein-10 (IP
      10) than nonuveitis controls. Active uveitis samples had higher levels of
      interleukin-6, interleukin-10, interferon-gamma, sVCAM, regulated on activation,
      normal T cell expressed and secreted (RANTES), and IP-10 than quiescent uveitis
      samples. Infectious uveitis was associated with higher levels of interleukin-10
      than noninfectious uveitis (P < .03 for all subgroups). No significant
      differences were found between cystoid macular edema (CME) and non-CME samples.
      CONCLUSIONS: Elevated levels of specific mediators were found in active and in
      infectious uveitis, but not in CME. Mediator profiles might lead to a better
      understanding of the pathogenesis of uveitis.

PMID- 16815286
TI  - Systemic absorption of 5-fluorouracil during vitrectomy.
AB  - PURPOSE: The aim of this study is to determine if systemic absorption is present
      after 5-fluorouracil (5FU) is used in the vitrectomy infusion. DESIGN: A two-case
      clinical study. METHODS: A catabolite of 5FU, alpha-fluoro-beta-alanine (FBAL),
      was measured in urine samples of two patients who underwent vitrectomy using 5FU
      in the infusion fluid. RESULTS: In both patients, FBAL was found in the urine
      samples collected up to 48 hours after the surgery, although in significantly
      different concentrations. CONCLUSIONS: The use of 5FU in the vitrectomy infusion
      fluid to prevent the formation of proliferative vitreoretinopathy may lead to
      significant general absorption and may be avoided in children and young adults.

PMID- 16815288
TI  - Intravitreal triamcinolone compared with macular laser grid photocoagulation for
      the treatment of cystoid macular edema.

PMID- 16815289
TI  - Sensitive and rapid polymerase chain reaction based diagnosis of mycotic
      keratitis through single stranded conformation polymorphism.

PMID- 16815290
TI  - Risk of sudden visual loss following filtration surgery in end-stage glaucoma.

PMID- 16815293
TI  - In vitro evaluation of alginate encapsulated adipose-tissue stromal cells for use
      as injectable bone graft substitute.
AB  - This study aims to investigate the survival and osteogenic behavior of murine
      derived adipose-tissue stromal cells (ATSCs) encapsulated in alginate
      microcapsules thereby instigating further studies in this cell delivery strategy
      for in vivo osteogenesis. Cell viability was quantified using a tetrazolium-based
      assay and osteogenic differentiation was evaluated by both alkaline-phosphatase
      (ALP) histochemistry and osteocalcin mRNA analysis. Following microencapsulation,
      cell numbers increased from 3.9 x 10(3) on day 1 to 7.8 x 10(3) on day 7 and
      maintained excellent viability in the course of 21-day culture. ALP was 6.9, 5.5,
      and 3.2 times higher than monolayer cultures on days 7, 14, and 21, respectively.
      In addition, osteocalcin mRNA was detectable in encapsulated cultures earlier
      (day 14) than monolayer cultures. We conclude that alginate microcapsules can act
      as three-dimensional matrix for ATSC proliferation and has potential for use as
      injectable, biodegradable scaffold in bone tissue engineering.

PMID- 16815294
TI  - Activation of the canonical Wnt/beta-catenin pathway enhances monocyte adhesion
      to endothelial cells.
AB  - Monocyte adhesion to vascular endothelium has been reported to be one of the
      early processes in the development of atherosclerosis. In an attempt to develop
      strategies to prevent or delay atherosclerosis progression, we analyzed effects
      of the Wnt/beta-catenin signaling pathway on monocyte adhesion to various human
      endothelial cells. Adhesion of fluorescein-labeled monocytes to various human
      endothelial cells was analyzed under a fluorescent microscope. Unlike sodium
      chloride, lithium chloride enhanced monocyte adhesion to endothelial cells in a
      dose-dependent manner. We further demonstrated that inhibitors for glycogen
      synthase kinase (GSK)-3beta or proteosome enhanced monocyte-endothelial cell
      adhesion. Results of semi-quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) indicated that activation of Wnt/beta-catenin pathway did not
      change expression levels of mRNA for adhesion molecules. In conclusion, the
      canonical Wnt/beta-catenin pathway enhanced monocyte-endothelial cell adhesion
      without changing expression levels of adhesion molecules.

PMID- 16815295
TI  - p73 and MDM2 confer the resistance of epidermoid carcinoma to cisplatin by
      blocking p53.
AB  - p73 responds to DNA damage and exerts its pro-apoptotic function. However, p73
      might contribute to the development of drug-resistance in certain tumor cells. In
      this study, we found that p73 and MDM2 correlate with cisplatin-resistant
      phenotype of human epidermoid carcinoma-derived cells. p73 and MDM2 were kept at
      low levels in the cisplatin-sensitive KB-3-1 cells, whereas p53 was induced to be
      phosphorylated at Ser-15 in response to cisplatin. In contrast, p73 and MDM2 were
      expressed at higher levels, and cisplatin-mediated p53 phosphorylation was
      undetectable in the cisplatin-resistant KCP-4 cells. Enforced expression of p73
      in KB-3-1 cells caused an accumulation of unphosphorylated form of p53 and MDM2,
      and conferred the cisplatin resistance. Collectively, our results suggest that a
      loss of the cisplatin sensitivity is at least in part due to a lack of cisplatin
      induced p53 phosphorylation, and p73 might cooperate with MDM2 to be involved in
      this process.

PMID- 16815296
TI  - Is Mongolian gerbil really adequate host animal for study of Helicobacter pylori
      infection-induced gastritis and cancer?
AB  - BACKGROUND: Many researches have been published to understand the pathogenesis
      and mechanism of Helicobacter pylori (Hp)-associated diseases, including
      gastritis followed by gastric cancer, using Mongolian gerbil (MG) model because
      Hp could be hardly inoculated in other animal species. The aim of this study was
      to evaluate the induction ability of heat shock protein (HSP70) and protective
      ability in the gastric mucosa of MG comparing with those of Sprague-Dawley (SD)
      rats, since HSP70 is a key molecule known to be involved in important biological
      activities such as apoptosis, carcinogenesis, and cytoprotection from cytotoxic
      damage. MATERIALS AND METHODS: Basal expression level and induction ability of
      gastric mucosal HSP70 were evaluated by immunoblotting and densitometric analysis
      in MG and SD rats before and after HSP-induction by zinc l-carnosine, gastric
      HSP70 inducer, administration. Mucosal protective ability against water-immersion
      stress-induced mucosal lesion was also compared. RESULTS: Basal expression level
      of HSP70 was not significantly different between MG and SD rats. However, HSP70
      induction by zinc derivatives was not observed in MG. Mucosal lesion induced by
      water-immersion stress was significantly severe in MG compared with SD rats.
      CONCLUSIONS: MG might be special (not ordinary) animal, in which HSP70-induction
      was absent and has extremely poor mucosal protective ability in view of HSP
      dependent cytoprotection in the gastric mucosa. Our results may suggest that MG
      is not an adequate animal to evaluate the effect of Hp-infection-associated
      gastric inflammation followed by development of gastric cancer.

PMID- 16815297
TI  - Mechanical strain-induced c-fos expression in pulmonary epithelial cell line
      A549.
AB  - Pulmonary epithelial cells are exposed to mechanical strain during physiological
      breathing and mechanical ventilation. It was not clear which style was more
      related with cell mechanotransduction. c-fos is known to be a component of a
      transcription factor, activator protein-1, which is induced by oxidative stress.
      The regulatory pathways involved in the rapid response of the AP-1 transcription
      factor, c-fos, to mechanical load in the human pulmonary epithelial cell line
      A549 were investigated using a four-point bending model. In an effort to better
      understand what processes are involved in mechanotransduction, we have examined
      whether and how soon c-fos induction occurs in human A549 shortly after the
      application of the different mechanical strains stimuli.

PMID- 16815298
TI  - The plasma membrane shuttling of CAPRI is related to regulation of mast cell
      activation.
AB  - The Ca(2+)-promoted Ras inactivator (CAPRI), a Ras GTPase-activating protein, is
      involved in the inactivation of mitogen-activated protein kinase pathway.
      However, a precise role of CAPRI in immune responses is still unknown. Here we
      showed that overexpression of CAPRI suppresses antigen-induced degranulation and
      cytokine production in mast cells (RBL cells). Antigen elicited the translocation
      of CAPRI to the plasma membrane from the cytoplasm, which was concomitant with
      the increase in the intracellular Ca(2+) concentration. The nuclear import of
      extracellular signal-regulated kinase 2 (ERK2) occurred after the re-localization
      of CAPRI to the cytoplasm in the mast cells, suggesting that the early phase of
      ERK2 activation is eliminated. A mutant of GAP-related domain, CAPRI(R472S),
      showed a feeble translocation to the plasma membrane but did not affect the
      degranulation, ERK2 activation, and cytokine production. The results suggested
      that the translocation of CAPRI to the plasma membranes regulates crucially
      cellular responses in mast cells.

PMID- 16815299
TI  - Vitronectin and collagen I differentially regulate osteogenesis in mesenchymal
      stem cells.
AB  - The roles of various soluble factors in promoting the osteogenic differentiation
      of adult mesenchymal stem cells (MSCs) have been widely studied, but little is
      known about how the extracellular matrix (ECM) instructs the phenotypic
      transition between growth and differentiation. To investigate this question, we
      cultured MSCs on purified vitronectin or type-I collagen, motivated by our
      earlier tissue engineering work demonstrating that MSC adhesion to polymer
      scaffolds is primarily mediated by the passive adsorption of these two ECM
      ligands from serum. Using alkaline phosphatase activity and matrix mineralization
      as indicators of the early and late stages of osteogenesis, respectively, we
      report here that both substrates supported differentiation, but the mechanism was
      substrate dependent. Specifically, osteogenesis on vitronectin correlated with
      enhanced focal adhesion formation, the activation of focal adhesion kinase (FAK)
      and paxillin, and the diminished activation of extracellular signal-regulated
      kinase (ERK) and phosphatidylinositol-3 kinase (PI3K) pathways. By contrast, MSCs
      on type-I collagen exhibited reduced focal adhesion formation, reduced activation
      of FAK and paxillin, and increased activation of ERK and PI3K. Inhibition of ERK
      and FAK blocked mineral deposition on both substrates, suggesting that the
      observed differences in signaling pathways ultimately converge to the same cell
      fate. Understanding these mechanistic differences is essential to predictably
      control the osteogenic differentiation of MSCs and widen their use in
      regenerative medicine.

PMID- 16815300
TI  - Abundant transcripts from retrotransposons are unstable in fully grown mouse
      oocytes.
AB  - One physiological function proposed for RNA interference (RNAi) is to constrain
      expression of repetitive elements and thereby reduce the incidence of
      retrotransposition. Consistent with this model is that inhibiting the RNAi
      pathway results in an increase in expression of repetitive elements in
      preimplantation mouse embryos. Mouse oocytes are essentially transcriptionally
      quiescent providing a unique opportunity to assess the stability of repetitive
      element-derived transcripts in these cells. We compared the transcriptome of
      freshly isolated fully grown germinal vesicle (GV)-intact oocytes to that of
      oocytes in which meiotic maturation in vitro was inhibited for 48 h by milrinone.
      Consistent with the aforementioned function for RNAi is that the abundance of
      only a relatively small number of transcripts decreased in the cultured oocytes,
      when compared to changes that occur during maturation or following fertilization,
      and of those, several belonged to mobile elements.

PMID- 16815301
TI  - Induction of CML28-specific cytotoxic T cell responses using co-transfected
      dendritic cells with CML28 DNA vaccine and SOCS1 small interfering RNA expression
      vector.
AB  - CML28 is an attractive target for antigen-specific immunotherapy. SOCS1
      represents an inhibitory control mechanism for DC antigen presentation and the
      magnitude of adaptive immunity. In this study, we evaluated the potential for
      inducing CML28-specific cytotoxic T lymphocytes (CTL) responses by dendritic
      cells (DCs)-based vaccination. We constructed a CML28 DNA vaccine and a SOCS1
      siRNA vector and then cotransfect monocyte-derived DCs. Flow cytometry analysis
      showed gene silencing of SOCS1 resulted in higher expressions of costimulative
      moleculars in DCs. Mixed lymphocyte reaction (MLR) indicated downregulation of
      SOCS1 stronger capability to stimulate proliferation of responder cell in DCs.
      The CTL assay revealed transfected DCs effectively induced autologous CML28
      specific CTL responses and the lytic activities induced by SOCS1-silenced DCs
      were significantly higher compared with those induced by SOCS1-expressing DCs.
      These results in our study indicates gene silencing of SOCS1 remarkably enhanced
      the cytotoxicity efficiency of CML28 DNA vaccine in DCs.

PMID- 16815302
TI  - Aptamer selection based on inhibitory activity using an evolution-mimicking
      algorithm.
AB  - In order to efficiently select aptamers that bind to and inhibit proteins, we
      developed a method that involves screening DNA aptamers based on their inhibitory
      activities using an evolution-mimicking algorithm after the pre-selection by
      SELEX. The value of this method was demonstrated by the identification of an
      inhibitor of Taq DNA polymerase in a unique single-stranded DNA library, which
      was expected to form a G-quartet structure. This method consists of selection via
      an inhibition assay, sequence shuffling, and mutation in silico. After six rounds
      of selection, the inhibitory activities of the aptamers had evolved
      significantly. This demonstrates the utility of this strategy for screening
      aptamers based on their inhibitory actions.

PMID- 16815303
TI  - Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus
      after transient forebrain ischemia.
AB  - We examined the phosphorylation state of tau factor in hippocampal delayed
      neuronal death (DND) after transient forebrain ischemia. A transient
      phosphorylation increase at serine 199/202 but not serine 396 of tau factor after
      transient ischemia was clearly observed. Intraventricular injections of
      olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited
      hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased
      phosphorylation at serine 199/202 and corresponded with an increase in GSK3
      phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3
      phosphorylate these sites after ischemia. We prepared recombinant normal human
      tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D
      tau40) in which 199/202 serines were changed to alanine by site-directed
      mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND
      while N-Tau40 did not. These data suggest that hyperphosphorylation at serine
      199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes
      to ischemic neuronal injury.

PMID- 16815304
TI  - Amelioration of bone loss in collagen-induced arthritis by neutralizing anti
      RANKL monoclonal antibody.
AB  - Receptor activator of NF-kappaB (RANK) and its ligand (RANKL) are pivotal
      regulators of osteoclast differentiation. RANK and RANKL also mediate T
      cell/dendritic cell (DC) interaction. Previous study has shown that RANK/RANKL
      interaction induces prolonged DC survival and antigen presentation. In the
      present study, we have newly established a hybridoma which produces neutralizing
      anti-RANKL monoclonal antibody (IK22-5). By treating collagen-induced arthritis
      (CIA) mice with IK22-5, we have investigated the role of RANKL in the
      pathogenesis of CIA. Although IK22-5 had no effect on immune responses or
      inflammation, it ameliorated bone loss at the site of inflammation. Histological
      analyses revealed that osteoclast formation was impaired at the site of joint
      inflammation in IK22-5-treated CIA mice. These results suggest the utility of
      anti-RANKL mAb for the prevention of osteoporosis associated with joint
      inflammation in RA.

PMID- 16815305
TI  - Genomic GC level, optimal growth temperature, and genome size in prokaryotes.
AB  - Two years ago, we showed that positive correlations between optimal growth
      temperature (T(opt)) and genome GC are observed in 15 out of the 20 families of
      prokaryotes we analyzed, thus indicating that "T(opt) is one of the factors that
      influence genomic GC in prokaryotes". Our results were disputed, but these
      criticisms were demonstrated to be mistaken and based on misconceptions. In a
      recent report, Wang et al. [H.C. Wang, E. Susko, A.J. Roger, On the correlation
      between genomic G+C content and optimal growth temperature in prokaryotes: data
      quality and confounding factors, Biochem. Biophys. Res. Commun. 342 (2006) 681
      684] criticize our results by stating that "all previous simple correlation
      analyses of GC versus temperature have ignored the fact that genomic GC content
      is influenced by multiple factors including both intrinsic mutational bias and
      extrinsic environmental factors". This statement, besides being erroneous, is
      surprising because it applies in fact not to ours but to the authors' article.
      Here, we rebut the points raised by Wang et al. and review some issues that have
      been a matter of debate, regarding the influence of environmental factors upon GC
      content in prokaryotes. Furthermore, we demonstrate that the relationship that
      exists between genome size and GC level is valid for aerobic, facultative, and
      microaerophilic species, but not for anaerobic prokaryotes.

PMID- 16815306
TI  - Identification of an intermolecular disulfide bond in barley hemoglobin.
AB  - Barley class-1 hemoglobin (Hb) and its mutated version (Cys(79) replaced by Ser)
      were overexpressed in Escherichia coli and purified to near homogeneity. Nano
      electrospray ionization mass spectrometry (nano-ESI MS) showed that the mutated
      barley Hb was more readily dissociated to a monomer and was more susceptible to
      denaturation than the native form. The mutated Hb was oxidized to the ferric
      state approximately 10(3) times faster than the non-mutated form. The increased
      oxidation of the mutated Hb was a result of substitution of the cysteine with a
      serine and not a consequence of monomer formation, per se. Tandem mass
      spectrometry (MS/MS) analysis revealed that Cys(79) participated in
      intermolecular S-S bond formation. The rates of nitric oxide scavenging by non
      mutated and mutated Hb were similar. We conclude that the cysteine residue is an
      important contributor to the quaternary and tertiary structure of barley
      hemoglobin. It however has no direct effect on nitric oxide-scavenging activity
      of barley Hb.

PMID- 16815307
TI  - Fgf16 is essential for pectoral fin bud formation in zebrafish.
AB  - Zebrafish pectoral fin bud formation is an excellent model for studying
      morphogenesis. Fibroblast growth factors (Fgfs) and sonic hedgehog (shh) are
      essential for pectoral fin bud formation. We found that Fgf16 was expressed in
      the apical ectodermal ridge (AER) of fin buds. A knockdown of Fgf16 function
      resulted in no fin bud outgrowth. Fgf16 is required for cell proliferation and
      differentiation in the mesenchyme and the AER of the fin buds, respectively.
      Fgf16 functions downstream of Fgf10, a mesenchymal factor, signaling to induce
      the expression of Fgf4 and Fgf8 in the AER. Fgf16 in the AER and shh in the zone
      of polarizing activity (ZPA) interact to induce and/or maintain each other's
      expression. These findings have revealed that Fgf16, a newly identified AER
      factor, plays a crucial role in pectoral fin bud outgrowth by mediating the
      interactions of AER-mesenchyme and AER-ZPA.

PMID- 16815308
TI  - A novel human zinc finger protein ZNF540 interacts with MVP and inhibits
      transcriptional activities of the ERK signal pathway.
AB  - Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes in
      cell signal transduction. Previous studies revealed that zinc finger proteins are
      involved in the regulation of the MAPK signaling pathways. Here we report the
      identification and characterization of a novel human zinc finger protein, ZNF540.
      The cDNA of ZNF540 is 3.3kb, encoding 660 amino acids in the nucleus and the
      cytoplasm. Northern blot analysis indicates that ZNF540 is expressed in most of
      the fetal tissues. Overexpression of FLAG-ZNF540 in COS-7 cells represses the
      transcriptional activities of SRE and ELK-1, which can be relieved by siRNA. MVP,
      one of MAPK scaffold proteins, is identified as a potential ZNF540-binding
      protein. This interaction is detected by a yeast two-hybrid assay, reporter gene
      assays, and co-immunoprecipitation. Taken together, these results suggest that
      ZNF540 may act as a transcriptional repressor in MAPK signaling pathway to
      mediate cellular functions.

PMID- 16815309
TI  - Characterization of the molecular pharmacology of AMD3100: a specific antagonist
      of the G-protein coupled chemokine receptor, CXCR4.
AB  - The chemokine receptor CXCR4 is widely expressed on different cell types, is
      involved in leukocyte chemotaxis, and is a co-receptor for HIV. AMD3100 has been
      shown to be a CXCR4 receptor antagonist, and to block HIV infection of T-tropic,
      X4-using, virus in vitro and in vivo. AMD3100 is an effective mobilizer of
      hematopoietic stem cells and is being investigated in clinical trials in multiple
      myeloma and non-Hodgkins lymphoma patients. Using the CCRF-CEM T-cell line that
      constitutively expresses CXCR4 we confirmed that AMD3100 was an antagonist of SDF
      1/CXCL12 ligand binding (IC50=651+/-37 nM). We have also shown that AMD3100
      inhibits SDF-1 mediated GTP-binding (IC50=27+/-2.2 nM), SDF-1 mediated calcium
      flux (IC50=572+/-190 nM), and SDF-1 stimulated chemotaxis (IC50=51+/-17 nM).
      AMD3100 did not inhibit calcium flux against cells expressing CXCR3, CCR1, CCR2b,
      CCR4, CCR5 or CCR7 when stimulated with their cognate ligands, nor did it inhibit
      receptor binding of LTB4. AMD3100 did not, on its own, induce a calcium flux in
      the CCRF-CEM cells, which express multiple GPCRs including CXCR4, CCR4 and CCR7.
      Furthermore, AMD3100 neither stimulated GTP-binding, an assay for GPCR
      activation, in CEM cell membranes; nor chemotaxis of CCRF-CEM cells. These data
      therefore demonstrate that AMD3100 is a specific antagonist of CXCR4, is not
      cross-reactive with other chemokine receptors, and is not an agonist of CXCR4.

PMID- 16815310
TI  - Protein S-glutathionylation and platelet anti-aggregating activity of disulfiram.
AB  - Blood platelets are central to haemostasis, and reactions in platelets involving
      sulfhydryl groups play important roles in platelet function. Reduced glutathione
      (GSH) plays an important role in platelet aggregation and glutathione-depleting
      chemicals inhibit platelet aggregation. The lipophilic drug disulfiram, because
      of its affinity for sulfhydryl groups, is a highly thiol-reacting agent. As a
      consequence, GSH and sulfhydryl groups of protein cysteines in human platelets,
      in analogy to other components of human blood, are a potential target of
      disulfiram. In the present study, we have shown that exposure of human platelets
      to disulfiram causes the depletion of platelet GSH and augmentation of mixed
      disulfides between GSH and protein sulfhydryl groups to form protein-glutathione
      mixed disulfides (S-glutathionylated proteins). The depletion of platelet GSH and
      the increase in S-glutathionylated proteins occurred at concentrations of
      disulfiram that inhibited platelet aggregation, suggesting that protein S
      glutathionylation is involved in the inhibition of platelet aggregation caused by
      disulfiram.

PMID- 16815311
TI  - Improving how we evaluate the toxicity of approved drugs.

PMID- 16815312
TI  - Genetic determinants of dose and clinical outcomes in patients receiving oral
      anticoagulants.

PMID- 16815313
TI  - VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction
      between both genotypes affects overanticoagulation.
AB  - OBJECTIVE: Our objective was to assess the effects of VKORC1 and CYP2C9 genotypes
      on severe overanticoagulation and time to achieve stability and their
      contributions to dose requirement during the initial phase of acenocoumarol
      treatment. METHODS: A prospective follow-up study was conducted at 2
      anticoagulation clinics in The Netherlands. We assessed the CYP2C9 genotype
      (CYP2C9*2 and CYP2C9*3 polymorphisms) and the VKORC1 C1173T genotype of the
      subjects and collected data on international normalized ratio, dose,
      comedication, and comorbidity. RESULTS: Of the 231 patients in the cohort, 150
      (64.9%) had a VKORC1 C1173T polymorphism and 84 (36.4%) had a CYP2C9*2 or
      CYP2C9*3 allele. Only carriers of a combination of a CYP2C9 polymorphism and a
      VKORC1 polymorphism had an increased risk of severe overanticoagulation compared
      with subjects with no polymorphism or only 1 polymorphism (hazard ratio, 3.83
      [95% confidence interval, 1.62-9.05]). The time to achieve stability was
      associated with the possession of the CYP2C9 genotype, not with the VKORC1
      genotype (hazard ratio for CYP2C9*3 allele compared with CYP2C9 wild type, 0.59
      [95% confidence interval, 0.40-0.87]). Patients with a VKORC1 polymorphism
      required significantly lower doses than VKORC1 CC wild-type patients. A larger
      part of the variability in dose requirement was explained by the VKORC1 genotype
      than by the CYP2C9 genotype (21.4% and 4.9%, respectively). CONCLUSION: Being a
      carrier of a combination of polymorphisms of VKORC1 and CYP2C9, rather than of
      one of these polymorphisms, is associated with severe overanticoagulation. The
      time to achieve stability is mainly associated with the CYP2C9 genotype.

PMID- 16815314
TI  - beta1-Adrenergic receptor polymorphisms influence the response to metoprolol
      monotherapy in patients with essential hypertension.
AB  - OBJECTIVES: The human beta(1)-adrenergic receptor, an important therapeutic
      target in cardiovascular diseases, has 2 common functional polymorphisms
      (Ser49Gly and Gly389Arg). Our study aimed to confirm that beta(1)-adrenergic
      receptor polymorphisms affect the blood pressure response to metoprolol
      monotherapy in the Chinese population with hypertension. METHODS: beta(1)
      Adrenergic receptor genotype was determined by polymerase chain reaction
      restriction fragment length polymorphism assay for 223 patients with essential
      hypertension. Sixty-one patients with certain beta(1)-adrenergic receptor
      diplotypes, 18 for 49Ser389Arg/49Ser389Arg, 15 for 49Ser389Arg/49Gly389Arg, 19
      for 49Ser389Gly/49Gly389Arg, and 9 for 49Ser389Gly/49Ser389Gly, were selected
      from those 61 for measurement of the antihypertensive effect of metoprolol.
      Patients were given 25 mg metoprolol every 12 hours for 4 weeks. Heart rate and
      blood pressure were measured weekly for the duration of metoprolol therapy.
      RESULTS: The descent of systolic blood pressure after metoprolol administration
      was significantly different among genotype groups (10.4% +/- 4.0%, 2.8% +/- 4.7%,
      and 1.1% +/- 1.5% for Arg389Arg, Gly389Arg, and Gly389Gly patients, respectively;
      P < .001). We also found a similar difference in changes of diastolic blood
      pressure (6.1% +/- 4.3%, 2.2% +/- 4.2%, and 0.9% +/- 4.0%, respectively; P <
      .001) and mean arterial pressure (8.1% +/- 3.5%, 2.5% +/- 3.0%, and 1.0% +/-
      2.5%, respectively; P > .001) for Arg389Arg, Gly389Arg, and Gly389Gly patients.
      Ser49Gly variance exhibited a smaller contribution to the antihypertensive effect
      of metoprolol. Systolic blood pressure decreased significantly in Ser49
      homozygous patients compared with Ser49Gly patients (8.4% +/- 3.2% versus 5.3% +/
      5.2%, P = .047). There was a highly significant relationship between diplotype
      and blood pressure during treatment. Systolic blood pressure significantly
      decreased in 49Ser389Arg/49Ser389Arg (12.0% +/- 3.8%, P < .001) and
      49Ser389Arg/49Gly389Arg (8.4% +/- 5.5%, P < .001) patients, with the decrease in
      the former being more pronounced (P = .023). We also found a significant decrease
      in diastolic blood pressure (6.5% +/- 4.7% versus 5.7% +/- 3.2%, respectively;
      both P < .001) and mean arterial pressure (8.8% +/- 3.2% versus 6.9% +/- 3.7%,
      respectively; both P < .001) in 49Ser389Arg/49Ser389Arg and
      49Ser389Arg/49Gly389Arg patients. However, blood pressure did not change
      significantly in 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients
      (all P > .05). CONCLUSIONS: beta(1)-Adrenergic receptor polymorphism was
      associated with different blood pressure responses to metoprolol therapy in
      patients with essential hypertension. 49Ser389Arg/49Ser389Arg and
      49Ser389Arg/49Gly389Arg patients were good responders to metoprolol therapy;
      49Ser389Arg/49Ser389Arg patients had a larger systolic blood pressure reduction
      than 49Ser389Arg/49Gly389Arg patients did. 49Ser389Gly/49Gly389Arg and
      49Ser389Gly/49Ser389Gly patients were nonresponders to metoprolol
      antihypertensive therapy.

PMID- 16815315
TI  - Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic
      comparative study.
AB  - OBJECTIVES: Our objectives were to investigate cytochrome P450 (CYP) 2C19
      polymorphism in Mexican Americans and compare the findings with those in 4 other
      ethnic groups. METHODS: The CYP2C19 genotype (n = 346) and S-mephenytoin
      hydroxylation phenotype (n = 220) were studied in a Mexican American population
      from Los Angeles County. Another 4 ethnic groups, African Americans (n = 236),
      whites (n = 273), East Asians (n = 161), and Southeast Asians (n = 80), were also
      recruited from Los Angeles County and genotyped and phenotyped for CYP2C19.
      RESULTS: The frequencies of CYP2C19*2 and *3 were 9.7% and 0.1%, respectively, in
      Mexican Americans, which were lower than those of the other 4 ethnic groups,
      ranging from 12.7% to 31.2% and 0.8% to 9.6%, respectively (P <or= .035). Seven
      Mexican American subjects were phenotyped as poor metabolizers. Thus the
      frequency of poor metabolizers in the Mexican American subjects was 3.2% (95%
      confidence interval, 0%-11.9%), which is similar to that of African Americans
      (5.4%) and whites (5.0%) and lower than that of East Asians (16.7%; P < .001) and
      Southeast Asians (23.9%; P < .001). Of the 7 poor metabolizers who were also
      genotyped, 2 were homozygous for the CYP2C19*2 alleles. CYP2C19*4, *5, *6, *7,
      and *8 were studied and did not account for the unexplained finding. The number
      of functional alleles among the extensive metabolizers correlated with the
      phenotype, suggesting a gene-dosage effect in Mexican Americans. CONCLUSIONS:
      This is the first study to investigate CYP2C19 polymorphism in Mexican Americans.
      The frequencies of the CYP2C19*2 and *3 alleles in Mexican Americans were found
      to be significantly lower than in other ethnic groups. This genotypic pattern
      might be responsible for the lower rate of poor metabolizers in Mexican Americans
      compared with other ethnic groups.

PMID- 16815316
TI  - Influences of proinflammatory and anti-inflammatory cytokine polymorphisms on
      eradication rates of clarithromycin-sensitive strains of Helicobacter pylori by
      triple therapy.
AB  - BACKGROUNDS AND AIMS: Polymorphisms of proinflammatory cytokines, such as
      interleukin (IL) 1beta and tumor necrosis factor (TNF) alpha, are associated with
      individual differences in gastric mucosal inflammation and acid inhibition in
      response to Helicobacter pylori infection. We investigated whether inflammation
      related cytokine polymorphisms would influence the eradication rates of H pylori
      by a triple-therapy regimen. METHODS: Three hundred sixty patients infected with
      clarithromycin-sensitive strains of H pylori were genotyped for IL1B -511, IL1RN,
      TNFA -857/-863/-1,031, IL10 -1,082/-819/-592, and CYP2C19 and underwent triple
      therapy for 1 week with a proton pump inhibitor (20 mg omeprazole, 30 mg
      lansoprazole, or 10 mg rabeprazole) twice daily, 400 mg clarithromycin twice
      daily, and 750 mg amoxicillin (INN, amoxicilline) twice daily. The influences of
      the previously mentioned polymorphisms on the eradication rates were analyzed.
      RESULTS: The intention-to-treat-based total eradication rate was 83.6% (301/360).
      The logistic regression analysis revealed that polymorphisms of CYP2C19 and IL1B 
      511 were independently associated with the eradication rates, but other cytokine
      polymorphisms were not associated with these rates. The eradication rates in
      patients with IL1B -511 C/C, C/T, and T/T genotypes were 72.2% (70/97), 87.7%
      (164/187), and 88.2% (67/76), respectively (P = .0017). When patients were
      stratified by CYP2C19 genotype status, IL1B -511 genotype-dependent differences
      in eradication rates were observed in homozygous extensive metabolizers (EMs) but
      not in heterozygous EMs and poor metabolizers of CYP2C19. The eradication rate in
      homozygous EM patients with the IL1B -511 C/C genotype was quite low (51.1%
      [22/43]). CONCLUSIONS: IL1B -511 polymorphism, but not IL1RN, TNFA, or IL10
      polymorphism, is one of the determinants of triple therapy for clarithromycin
      sensitive strains of H pylori in CYP2C19 homozygous EMs.

PMID- 16815317
TI  - CYP3A5*3 influences sirolimus oral clearance in de novo and stable renal
      transplant recipients.
AB  - BACKGROUND: The low and highly variable oral bioavailability of the
      immunosuppressant sirolimus is thought to result partly from genetic polymorphism
      of the CYP3A5 gene. METHODS: This study aimed to evaluate the contribution of the
      CYP3A5 single-nucleotide polymorphism A6986G to the interindividual variability
      of sirolimus pharmacokinetics in 47 renal transplant patients at steady state, 21
      of whom were also followed up for the first 3 months after transplantation. The
      patients were administered sirolimus, mycophenolate mofetil, and corticosteroids
      but no calcineurin inhibitor. They were genotyped for CYP3A5*3 by use of real
      time quantitative polymerase chain reaction based on the 5'-nuclease allelic
      discrimination assay. Full sirolimus blood concentration profiles were measured
      at steady state (3 months after transplantation or more) in all patients, as well
      as at weeks 1 and 2 and month 1 in 21 of these patients, by use of liquid
      chromatography-tandem mass spectrometry. The sirolimus area under the
      concentration-time curve (AUC) was calculated via the standard noncompartmental
      approach. Maximal concentration (C(max)) and trough level (C(0)) values were
      measured. RESULTS: Significantly lower AUC/dose, C(max)/dose, and C(0)/dose
      values were found at steady state (n = 47) in individuals carrying at least 1
      CYP3A5*1 allele (n = 6) than in *3/*3 patients (26.6 +/- 15.7 versus 51.1 +/-
      21.1 [P = .008], 4.8 +/- 3.3 versus 7.7 +/- 3.3 [P = .02], and 1.5 +/- 0.8 versus
      3.0 +/- 1.5 [P = .01], respectively), as well as during all posttransplant
      periods in the subgroup of 21 patients who were followed up for the first 3
      months after transplantation (n = 21) (P < .05 always). Patients with the
      CYP3A5*1/*1 and *1/*3 genotypes required a significantly higher sirolimus daily
      dose to achieve the same blood concentration at steady state as *3/*3 patients.
      In patients followed up for the first 3 months after transplantation, C(0) levels
      within the target range were only achieved after 1 to 3 months of repeated dosing
      and dose adjustment in both genotypic groups. CONCLUSION: These results confirm
      that sirolimus metabolic activity and oral clearance are significantly decreased
      in patients who are homozygous for the CYP3A5*3 single-nucleotide polymorphism
      and suggest that the determination of this polymorphism could be useful for a
      priori dose adjustment of sirolimus, given the long half-life of this drug.

PMID- 16815318
TI  - Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism:
      implication for optimization of breast cancer treatment.
AB  - BACKGROUND AND OBJECTIVES: N-Desmethyltamoxifen (NDM), a major primary metabolite
      of tamoxifen, is hydroxylated by cytochrome P450 (CYP) 2D6 to yield endoxifen.
      Because of its high antiestrogenic potency, endoxifen may play an important role
      in the clinical activity of tamoxifen. We conducted a prospective trial in 158
      patients with breast cancer who were taking tamoxifen to further understand the
      effect of CYP2D6 genotype and concomitant medications on endoxifen plasma
      concentrations. METHODS: Medication history, genotype for 33 CYP2D6 alleles, and
      plasma concentrations of tamoxifen and its metabolites were determined at the
      fourth month of tamoxifen treatment. RESULTS: By use of a mixture model approach,
      endoxifen plasma concentration identified 2 phenotypic groups, whereas 4 were
      defined by the endoxifen/NDM plasma concentration ratio. Three distinct genotype
      groups were identified in the distribution of endoxifen/NDM ratio: (1) low ratios
      composed of patients lacking any functional allele (mean, 0.04 +/- 0.02); (2)
      intermediate ratios represented by patients with 1 active allele (mean, 0.08 +/-
      0.04); and (3) high ratios composed of patients with 2 or more functional alleles
      (mean, 0.15 +/- 0.09). Endoxifen/NDM plasma ratios were significantly different
      between these groups (P < .001). The mean endoxifen plasma concentration was
      significantly lower in CYP2D6 extensive metabolizers who were taking potent
      CYP2D6 inhibitors than in those who were not taking CYP2D6 inhibitors (23.5 +/-
      9.5 nmol/L versus 84.1 +/- 39.4 nmol/L, P < .001). CONCLUSION: CYP2D6 genotype
      and concomitant potent CYP2D6 inhibitors are highly associated with endoxifen
      plasma concentration and may have an impact on the response to tamoxifen therapy.
      These iterative approaches may be valuable in the study of other complex genotype
      phenotype relationships.

PMID- 16815320
TI  - Acute effects of sumatriptan on aortic blood pressure, stiffness, and pressure
      waveform.
AB  - BACKGROUND AND OBJECTIVES: Sumatriptan, a 5-hydroxytryptamine (HT)(1B/1D)
      receptor agonist, is an effective acute antimigraine drug. Because of its
      vasoconstrictor activity, it is contraindicated in patients at high risk for
      adverse cardiovascular events. Acute antimigraine drugs without vasoconstrictor
      effects are currently being developed, and sensitive, noninvasive techniques by
      which to detect drug-induced vascular effects would facilitate their clinical
      development. The effects of sumatriptan on aortic blood pressure, stiffness, and
      pressure waveform have not been assessed previously in detail. METHODS: A
      randomized, placebo-controlled, double-blind, 4-way crossover study was performed
      in 12 healthy subjects. Each subject received 25, 50, and 100 mg sumatriptan and
      placebo as single oral doses. Vascular measurements, including oscillometric
      blood pressure measurement, arterial ultrasound, systolic pulse contour analysis,
      and aortic pulse wave velocity measurement, were performed at baseline and 30,
      90, and 150 minutes after drug administration. RESULTS: Compared with placebo and
      expressed as weighted mean +/- SD, 100 mg sumatriptan increased aortic systolic
      blood pressure by 6 +/- 5 mm Hg (P < .01), aortic pulse wave velocity by 0.5 +/-
      0.5 m/s (P < .01), and aortic augmentation index by 13% +/- 6% (P < .0001). The
      increase in aortic systolic blood pressure was larger compared with the increase
      in brachial systolic blood pressure (P < .0001). Significant vascular effects
      were already detected after the lowest dose of sumatriptan by systolic pulse
      contour analysis and arterial ultrasound. CONCLUSION: These findings show that
      therapeutic doses of sumatriptan acutely increase aortic blood pressure,
      stiffness, and augmentation index. Noninvasive systolic pulse contour analysis
      and arterial ultrasound may facilitate detection of drug-induced vascular effects
      in early clinical trials.

PMID- 16815319
TI  - Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of
      induction by rifampin and ethnicity.
AB  - AIM: The aim of this study was to investigate the activity of the drug
      metabolizing enzyme cytochrome P450 (CYP) 2B6 before and after in vivo induction
      by rifampin (INN, rifampicin) in white subjects and Chinese subjects by use of
      the probe drug bupropion (INN, amfebutamone). METHODS: Healthy male white
      subjects (n = 9) and Chinese subjects (n = 9) (age range, 19-34 years) of known
      CYP2B6 genotype received orally administered bupropion (Zyban SR, 150 mg) alone
      and during daily treatment with rifampin (600 mg). Blood samples were taken for
      up to 72 hours after each bupropion dose, and plasma concentrations of bupropion
      and its active metabolites, hydroxybupropion, threohydrobupropion, and
      erythrohydrobupropion, were measured by HPLC. The subjects' CYP2B6 genotype was
      determined by use of a matrix-assisted laser desorption /ionization-time of
      flight (MALDI-TOF) mass spectrometry assay. RESULTS: Rifampin treatment increased
      the apparent clearance of bupropion in Chinese subjects and white subjects
      combined (n = 16) from 2.6 L x h(-1) x kg(-1) (95% confidence interval [CI], 2.3
      3.0 L x h(-1) x kg(-1)) after bupropion alone to 7.9 L x h(-1) x kg(-1) (95% CI,
      6.8-10.1 L x h(-1) x kg(-1)) during rifampin treatment. Rifampin treatment
      decreased the half-life of bupropion from 15.9 hours (95% CI, 13.5-20.4 hours) to
      8.2 hours (95% CI, 6.7-12.4 hours). Rifampin treatment increased the
      hydroxybupropion maximum concentration from 395 ng/mL (95% CI, 341-497 ng/mL) to
      548 ng/mL (95% CI, 490-638 ng/mL), decreased the area under the concentration
      time curve extrapolated to infinity of hydroxybupropion from 14.7 microg x h/mL
      (95% CI, 12.7-18.4 microg x h/mL) to 8.4 microg x h/mL (95% CI, 7.4-10.2 microg x
      h/mL), and reduced the elimination half-life of hydroxybupropion from 21.9 hours
      (95% CI, 20.3-24.0 hours) to 10.7 hours (95% CI, 8.6-14.5 hours). There was no
      significant difference in the pharmacokinetics of bupropion or hydroxybupropion
      between white subjects and Chinese subjects before and after treatment with
      rifampin, once corrected for body weight. CONCLUSIONS: Rifampin significantly
      induces CYP2B6 activity in vivo, and the clinical consequences of potential
      interactions between rifampin and CYP2B6 substrates deserve further
      investigation. Rifampin appears to induce the elimination of hydroxybupropion.
      Differences in bupropion pharmacokinetics that were observed between white
      subjects and Chinese subjects can be attributed to differences in body weight,
      suggesting that, for a given subject weight, CYP2B6 activity is similar in white
      subjects and Chinese subjects.

PMID- 16815321
TI  - Misestimating the role of an active metabolite when modeling the effects after
      administration of the parent compound only.

PMID- 16815322
TI  - The prevalence and correlates of eating disorders in the National Comorbidity
      Survey Replication.
AB  - BACKGROUND: Little population-based data exist on the prevalence or correlates of
      eating disorders. METHODS: Prevalence and correlates of eating disorders from the
      National Comorbidity Replication, a nationally representative face-to-face
      household survey (n = 9282), conducted in 2001-2003, were assessed using the WHO
      Composite International Diagnostic Interview. RESULTS: Lifetime prevalence
      estimates of DSM-IV anorexia nervosa, bulimia nervosa, and binge eating disorder
      are .9%, 1.5%, and 3.5% among women, and .3% .5%, and 2.0% among men. Survival
      analysis based on retrospective age-of-onset reports suggests that risk of
      bulimia nervosa and binge eating disorder increased with successive birth
      cohorts. All 3 disorders are significantly comorbid with many other DSM-IV
      disorders. Lifetime anorexia nervosa is significantly associated with low current
      weight (body-mass index <18.5), whereas lifetime binge eating disorder is
      associated with current severe obesity (body-mass index > or =40). Although most
      respondents with 12-month bulimia nervosa and binge eating disorder report some
      role impairment (data unavailable for anorexia nervosa since no respondents met
      criteria for 12-month prevalence), only a minority of cases ever sought
      treatment. CONCLUSIONS: Eating disorders, although relatively uncommon, represent
      a public health concern because they are frequently associated with other
      psychopathology and role impairment, and are frequently under-treated.

PMID- 16815323
TI  - Neurotrophins and dementia--keeping in touch.
AB  - Down's syndrome patients develop dementia similar to Alzheimer's disease and show
      elevated levels of amyloid precursor protein in brain. Two papers in this issue
      of Neuron show that reduced retrograde transport or signaling of the
      neurotrophins NGF or BDNF, respectively, may account for the neuronal pathology
      in mouse models of Down's syndrome.

PMID- 16815324
TI  - Rustling synaptic vesicle cargo after exocytosis.
AB  - In this issue of Neuron, Voglmaier et al. provide new evidence that the retrieval
      of synaptic vesicle transporters after exocytosis proceeds along at least two
      different endocytic pathways. This work provides new insight into the mechanisms
      of sorting synaptic vesicle cargo at the cell surface.

PMID- 16815325
TI  - A new locus for synaptic plasticity in cerebellar circuits.
AB  - Experimental and computational analyses of cerebellar function indicate that
      excitatory synapses onto deep nucleus neurons are likely to be a critical site of
      plasticity during motor learning. In this issue of Neuron, Pugh and Raman report
      that unconventional stimulus protocols can drive synaptic plasticity in the deep
      cerebellar nuclei.

PMID- 16815326
TI  - Progress in understanding spatial coordinate systems in the primate brain.
AB  - A new study in this issue of Neuron shows that when monkeys reach to a visual
      target, neurons in the dorsal premotor cortex compare the location of the target,
      the hand, and the point of visual fixation. The neurons therefore encode space
      through a combination of eye-centered and hand-centered coordinates.

PMID- 16815327
TI  - Cognitive control signals in visual cortex: flashes meet spotlights.
AB  - At the intersection of two intensely belabored fields, primary visual cortex (V1)
      function and neural mechanisms of cognitive control, Jack et al. (in this issue
      of Neuron) report a neural signal that is neither related to stimulus
      representation nor spatial attention. Instead, this endogenous signal correlates
      with task structure and raises new questions.

PMID- 16815328
TI  - Drosophila neuroblast asymmetric cell division: recent advances and implications
      for stem cell biology.
AB  - Asymmetric cell division is an evolutionarily conserved mechanism widely used to
      generate cellular diversity during development. Drosophila neuroblasts have been
      a useful model system for studying the molecular mechanisms of asymmetric cell
      division. In this minireview, we focus on recent progress in understanding the
      role of heterotrimeric G proteins and their regulators in asymmetric spindle
      geometry, as well as the role of an Inscuteable-independent microtubule pathway
      in asymmetric localization of proteins in neuroblasts. We also discuss issues of
      progenitor proliferation and differentiation associated with asymmetric cell
      division and their broader implications for stem cell biology.

PMID- 16815329
TI  - In vivo restoration of physiological levels of truncated TrkB.T1 receptor rescues
      neuronal cell death in a trisomic mouse model.
AB  - Imbalances in neurotrophins or their high-affinity Trk receptors have long been
      reported in neurodegenerative diseases. However, a molecular link between these
      gene products and neuronal cell death has not been established. In the trisomy 16
      (Ts16) mouse there is increased apoptosis in the cortex, and hippocampal neurons
      undergo accelerated cell death that cannot be rescued by administration of brain
      derived neurotrophic factor (BDNF). Ts16 neurons have normal levels of the TrkB
      tyrosine kinase receptor but an upregulation of the TrkB.T1 truncated receptor
      isoform. Here we show that restoration of the physiological level of the TrkB.T1
      receptor by gene targeting rescues Ts16 cortical cell and hippocampal neuronal
      death. Moreover, it corrects resting Ca2+ levels and restores BDNF-induced
      intracellular signaling mediated by full-length TrkB in Ts16 hippocampal neurons.
      These data provide a direct link between neuronal cell death and abnormalities in
      Trk neurotrophin receptor levels.

PMID- 16815330
TI  - Increased App expression in a mouse model of Down's syndrome disrupts NGF
      transport and causes cholinergic neuron degeneration.
AB  - Degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to
      cognitive dysfunction in Alzheimer's disease (AD) and Down's syndrome (DS). We
      used Ts65Dn and Ts1Cje mouse models of DS to show that the increased dose of the
      amyloid precursor protein gene, App, acts to markedly decrease NGF retrograde
      transport and cause degeneration of BFCNs. NGF transport was also decreased in
      mice expressing wild-type human APP or a familial AD-linked mutant APP; while
      significant, the decreases were less marked and there was no evident degeneration
      of BFCNs. Because of evidence suggesting that the NGF transport defect was intra
      axonal, we explored within cholinergic axons the status of early endosomes (EEs).
      NGF-containing EEs were enlarged in Ts65Dn mice and their App content was
      increased. Our study thus provides evidence for a pathogenic mechanism for DS in
      which increased expression of App, in the context of trisomy, causes abnormal
      transport of NGF and cholinergic neurodegeneration.

PMID- 16815331
TI  - p120 catenin regulates dendritic spine and synapse development through Rho-family
      GTPases and cadherins.
AB  - Both the cadherin-catenin complex and Rho-family GTPases have been shown to
      regulate dendrite development. We show here a role for p120 catenin (p120ctn) in
      regulating spine and synapse formation in the developing mouse brain. p120catenin
      gene deletion in hippocampal pyramidal neurons in vivo resulted in reduced spine
      and synapse densities along dendrites. In addition, p120 catenin loss resulted in
      reduced cadherin levels and misregulation of Rho-family GTPases, with decreased
      Rac1 and increased RhoA activity. Analyses in vitro indicate that the reduced
      spine density reflects aberrant Rho-family GTPase signaling, whereas the effects
      on spine maturation appear to result from reduced cadherin levels and possibly
      aberrant Rho-family GTPase signaling. Thus, p120ctn acts as a signal coordinator
      between cadherins and Rho-family GTPases to regulate cytoskeletal changes
      required during spine and synapse development.

PMID- 16815332
TI  - Highwire restrains synaptic growth by attenuating a MAP kinase signal.
AB  - Highwire is an extremely large, evolutionarily conserved E3 ubiquitin ligase that
      negatively regulates synaptic growth at the Drosophila NMJ. Highwire has been
      proposed to restrain synaptic growth by downregulating a synaptogenic signal.
      Here we identify such a downstream signaling pathway. A screen for suppressors of
      the highwire synaptic overgrowth phenotype yielded mutations in wallenda, a MAP
      kinase kinase kinase (MAPKKK) homologous to vertebrate DLK and LZK. wallenda is
      both necessary for highwire synaptic overgrowth and sufficient to promote
      synaptic overgrowth, and synaptic levels of Wallenda protein are controlled by
      Highwire and ubiquitin hydrolases. highwire synaptic overgrowth requires the MAP
      kinase JNK and the transcription factor Fos. These results suggest that Highwire
      controls structural plasticity of the synapse by regulating gene expression
      through a MAP kinase signaling pathway. In addition to controlling synaptic
      growth, Highwire promotes synaptic function through a separate pathway that does
      not require wallenda.

PMID- 16815333
TI  - Distinct endocytic pathways control the rate and extent of synaptic vesicle
      protein recycling.
AB  - Synaptic vesicles have been proposed to form through two mechanisms: one directly
      from the plasma membrane involving clathrin-dependent endocytosis and the adaptor
      protein AP2, and the other from an endosomal intermediate mediated by the adaptor
      AP3. However, the relative role of these two mechanisms in synaptic vesicle
      recycling has remained unclear. We now find that vesicular glutamate transporter
      VGLUT1 interacts directly with endophilin, a component of the clathrin-dependent
      endocytic machinery. In the absence of its interaction with endophilin, VGLUT1
      recycles more slowly during prolonged, high-frequency stimulation. Inhibition of
      the AP3 pathway with brefeldin A rescues the rate of recycling, suggesting a
      competition between AP2 and -3 pathways, with endophilin recruiting VGLUT1 toward
      the faster AP2 pathway. After stimulation, however, inhibition of the AP3 pathway
      prevents the full recovery of VGLUT1 by endocytosis, implicating the AP3 pathway
      specifically in compensatory endocytosis.

PMID- 16815334
TI  - Developmentally regulated, combinatorial RNA processing modulates AMPA receptor
      biogenesis.
AB  - The subunit composition determines AMPA receptor (AMPA-R) function and
      trafficking. Mechanisms underlying channel assembly are thus central to the
      efficacy and plasticity of glutamatergic synapses. We previously showed that RNA
      editing at the Q/R site of the GluR2 subunit contributes to the assembly of AMPA
      R heteromers by attenuating formation of GluR2 homotetramers. Here we report that
      this function of the Q/R site depends on subunit contacts between adjacent ligand
      binding domains (LBDs). Changes of LBD interface contacts alter GluR2 assembly
      properties, forward traffic, and expression at synapses. Interestingly,
      developmentally regulated RNA editing within the LBD (at the R/G site) produces
      analogous effects. Our data reveal that editing to glycine reduces the self
      assembly competence of this critical subunit and slows GluR2 maturation in the
      endoplasmic reticulum (ER). Therefore, RNA editing sites, located at strategic
      subunit interfaces, shape AMPA-R assembly and trafficking in a developmentally
      regulated manner.

PMID- 16815335
TI  - Alternative N-terminal domains of PSD-95 and SAP97 govern activity-dependent
      regulation of synaptic AMPA receptor function.
AB  - PSD-95 and SAP97 are scaffolding proteins that have been implicated in regulating
      AMPA receptor incorporation and function at synapses. Gain- and loss-of-function
      approaches, however, have generated conflicting results. To minimize adaptations
      during development and potential dominant-negative effects of overexpression, we
      have combined silencing of endogenous PSD-95 in mature neurons with heterologous
      expression of specific SAP97 or PSD-95 isoforms. We find that both PSD-95 and
      SAP97 contain alternative N termini expressing either double cysteines that
      normally are palmitoylated (alpha-isoforms) or an L27 domain (beta-isoforms).
      Whereas alpha-isoforms of PSD-95 and SAP97 influence AMPA receptor-mediated
      synaptic strength independent of activity, the effects of beta-isoforms are
      regulated by activity in a CaMKII-dependent manner. Importantly, the synaptic
      effects of the beta-isoforms are masked by the endogenous alpha-isoform of PSD
      95. These results demonstrate that the different N termini of the predominant
      endogenous forms of PSD-95 (alpha-isoform) and SAP97 (beta-isoform) govern their
      role in regulating synaptic function.

PMID- 16815336
TI  - Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor
      activation followed by postinhibitory rebound current.
AB  - Behavioral and computational studies predict that synaptic plasticity of
      excitatory mossy fiber inputs to cerebellar nuclear neurons is required for
      associative learning, but standard tetanization protocols fail to potentiate
      nuclear cell EPSCs in mouse cerebellar slices. Nuclear neurons fire action
      potentials spontaneously unless strongly inhibited by Purkinje neurons, raising
      the possibility that plasticity-triggering signals in these cells differ from
      those at classical Hebbian synapses. Based on predictions of neuronal activity
      during delay eyelid conditioning, we developed quasi-physiological induction
      protocols consisting of high-frequency mossy fiber stimulation and postsynaptic
      hyperpolarization. Robust, NMDA receptor-dependent potentiation of nuclear cell
      EPSCs occurred with protocols including a 150-250 ms hyperpolarization in which
      mossy fiber stimulation preceded a postinhibitory rebound depolarization. Mossy
      fiber stimulation potentiated EPSCs even when postsynaptic spiking was prevented
      by voltage-clamp, as long as rebound current was evoked. These data suggest that
      Purkinje cell inhibition guides the strengthening of excitatory synapses in the
      cerebellar nuclei.

PMID- 16815338
TI  - Separate modulations of human V1 associated with spatial attention and task
      structure.
AB  - Functional magnetic resonance imaging (fMRI) was used while normal human
      volunteers engaged in simple detection and discrimination tasks, revealing
      separable modulations of early visual cortex associated with spatial attention
      and task structure. Both modulations occur even when there is no change in
      sensory stimulation. The modulation due to spatial attention is present
      throughout the early visual areas V1, V2, V3, and VP, and varies with the
      attended location. The task structure activations are strongest in V1 and are
      greater in regions that represent more peripheral parts of the visual field.
      Control experiments demonstrate that the task structure activations cannot be
      attributed to visual, auditory, or somatosensory processing, the motor response
      for the detection/discrimination judgment, or oculomotor responses such as blinks
      or saccades. These findings demonstrate that early visual areas are modulated by
      at least two types of endogenous signals, each with distinct cortical
      distributions.

PMID- 16815337
TI  - Dorsal premotor neurons encode the relative position of the hand, eye, and goal
      during reach planning.
AB  - When reaching to grasp an object, we often move our arm and orient our gaze
      together. How are these movements coordinated? To investigate this question, we
      studied neuronal activity in the dorsal premotor area (PMd) and the medial
      intraparietal area (area MIP) of two monkeys while systematically varying the
      starting position of the hand and eye during reaching. PMd neurons encoded the
      relative position of the target, hand, and eye. MIP neurons encoded target
      location with respect to the eye only. These results indicate that whereas MIP
      encodes target locations in an eye-centered reference frame, PMd uses a relative
      position code that specifies the differences in locations between all three
      variables. Such a relative position code may play an important role in
      coordinating hand and eye movements by computing their relative position.

PMID- 16815339
TI  - Association between dopamine D4 receptor (DRD4) gene polymorphisms and novelty
      elicited auditory event-related potentials in preschool children.
AB  - We investigated associations of the exon III repeat and the -521 C/T
      polymorphisms of the DRD4 gene with novelty-elicited auditory ERP components and
      behavioral resistance to distraction in 57 healthy, typically developing 6-year
      old children. Dopamine-related gene polymorphisms have previously been linked to
      processes directing focused attention. We did not find associations between the 7
      repeat allele or the T.7 haplotype and the early ERP responses suggesting that
      DRD4 polymorphisms did not affect the detection of novelty. However, the same
      polymorphisms affected the late negative components (LN1 and LN2). Late
      negativities elicited by deviant and novel sounds have been regarded as
      reflecting reorientation after distraction or additional processing of new
      information. Children carrying the T.7 haplotype had significantly smaller LN1
      and LN2 amplitudes. The presence of the T.7 haplotype also significantly enhanced
      behavioral resistance to distraction. We suggest that less distraction in T.7
      carriers led to less reorienting activity (reflected by the LN components). We
      also speculate that activation of less sensitive and fewer D4 receptors (as with
      the T.7 haplotype) is less effective in modulating GABAergic inhibitory
      signaling, which in turn is reflected in smaller LN amplitudes.

PMID- 16815340
TI  - Noise-induced up-regulation of NTPDase3 expression in the rat cochlea:
      Implications for auditory transmission and cochlear protection.
AB  - Stimuli such as noise or hypoxia can induce a release of ATP into the cochlear
      fluid spaces. At nanomolar concentrations, ATP affects neurotransmission and
      electrochemical regulation of sound transduction. At higher concentrations, ATP
      may exert cytotoxicity acting on specific P2X(7) receptor subunits, thus
      contributing to the pathophysiology of noise-induced cochlear injury.
      Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are pivotal to
      regulation of extracellular nucleotide concentrations and therefore P2 receptor
      signaling in the cochlea. Here, we characterize the distribution of NTPDase3
      ectonucleotidase (preferentially hydrolyzes ATP over ADP) in cochlear tissues and
      investigate the effect of noise exposure on NTPDase3 expression. Marked NTPDase3
      immunoreactivity in the primary afferent neurones of the spiral ganglion,
      extending in the distal neurite processes to the synapses beneath the inner and
      outer hair cells, suggests involvement in auditory neurotransmission.
      Immunolabeling in the lateral wall and epithelial cells lining the cochlear
      partition was also evident. Semi-quantitative immunohistochemistry revealed
      increased NTPDase3 immunolabeling in the synaptic regions of the inner and outer
      hair cells at sound intensities that induce temporary threshold shift. The
      results suggest a role for NTPDase3 in regulating ATP signaling associated
      primarily with auditory neurotransmission, and the potential neuroprotective
      nature of noise-induced up-regulation of this ectonucleotidase in the cochlea.

PMID- 16815341
TI  - Immunolocalization of NaV1.2 channel subtypes in rat and cat brain and spinal
      cord with high affinity antibodies.
AB  - High titer polyclonal antibodies were produced in rabbit against a peptide unique
      to NaV1.2 sodium channels. NaV1.2 antibodies displayed 500,000-fold greater
      affinity for the NaV1.2 peptide compared with NaV1.1 or NaV1.3 peptides from the
      same region. These antibodies, when coupled to Sepharose beads, retained
      saxitoxin binding sites from solubilized rat brain membranes. Eluted protein from
      this antibody-affinity column was recognized by antibodies directed against
      neuronal voltage-gated sodium channels. Rabbit antibodies, which had been
      partially purified, were used in immunocytochemical localization of the NaV1.2
      channel in 50 microm rat brain slices at dilutions of 1:1000 or 1:2000. NaV1.2
      channels were predominately localized in unmyelinated fibers in the cortex,
      hippocampus, spinal cord and hypothalamus. Varicosities were seen in fiber
      staining which may reflect true varicosities in the fiber or simply varying
      densities of sodium channels along the fiber. Cell body staining with the NaV1.2
      antibody was primarily observed in the hypothalamus. Antibody staining in the
      cerebellum was complex, with staining observed primarily in posterior lobes and
      considerably lower amounts of staining observed in anterior lobes. Specific
      staining was limited to fibers located in the granule and molecular layer, in an
      orientation consistent with granule cell unmyelinated axon labeling.

PMID- 16815342
TI  - The structure of the O-polysaccharide from the lipopolysaccharide of Providencia
      alcalifaciens O36 containing 3-deoxy-d-manno-oct-2-ulosonic acid.
AB  - An oligosaccharide that corresponds to the repeating unit of the O-polysaccharide
      was obtained by mild acid degradation of the lipopolysaccharide of Providencia
      alcalifaciens O36. Structural studies of the oligosaccharide and O-deacylated
      lipopolysaccharide were performed using sugar and methylation analyses along with
      (1)H and (13)C NMR spectroscopy, including 2D (1)H,(1)H COSY, TOCSY, ROESY, and H
      detected (1)H,(13)C HSQC and HMBC experiments. It was found that the O
      polysaccharide is built up of linear trisaccharide repeating units containing 2
      acetamido-2-deoxyglucose, 6-deoxy-l-talose (l-6dTal), and 3-deoxy-d-manno-oct-2
      ulosonic acid (Kdo) and has the following structure. [structure: see text]

PMID- 16815343
TI  - A facile synthesis of 1,6-dideoxynojirimycin from L-sorbose.
AB  - A practical synthesis of 1,6-dideoxynojirimycin, a potent glycosidase inhibitor,
      starting from L-sorbose, is described.

PMID- 16815344
TI  - Review of therapies for immune thrombocytopenic purpura.

PMID- 16815345
TI  - Recent advances in the treatment of childhood immune thrombocytopenic purpura.
AB  - Immune thrombocytopenic purpura (ITP), the most common bleeding disorder in
      childhood, is a benign condition that typically resolves within 6 months
      following diagnosis. While all would agree on drug treatment for children with
      severe hemorrhage, management strategies of the minimally symptomatic child with
      a very low platelet count can vary widely. The case for treatment is based
      primarily on the risk for the uncommon complication of intracranial hemorrhage or
      other serious bleeding. Numerous clinical studies clearly indicate that immune
      globulins (intravenous immune globulin [IVIg] or anti-D) and corticosteroid
      therapy (prednisone and megadose methylprednisolone) are effective in rapidly
      raising platelet counts. However, physicians must ultimately decide whether to
      use drug therapy for a patient with minimal symptoms and low platelet count or
      adopt an "observation-only" approach. With this background, three fundamental
      questions emerge when evaluating different clinical strategies and potential
      outcomes: (1) Which children with ITP need treatment? (2) Which pharmacologic
      agent best accomplishes the goals of drug treatment? (3) Can physicians better
      predict the outcome of treatments?

PMID- 16815346
TI  - Treatment of immune thrombocytopenic purpura in adults.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a hematologic disorder characterized
      by the destruction of antibody-coated platelets in the reticuloendothelial
      system. Whereas 70% to 80% of children experience the acute form of the disease
      and recover within a few weeks or months after diagnosis, most adults have
      persistent disease and will require therapy. Principles of management are largely
      predicated on the extent of thrombocytopenia and symptoms of disease. Minimizing
      the toxicity associated with treatment while achieving hemostatic platelet counts
      are essential goals of treatment. Although there are numerous therapeutic
      options, neither consensus among experts nor clear algorithms to treat this
      complex disease exist. This article will review appropriate treatment options
      available for adult patients with ITP prior to splenectomy, at splenectomy, and
      following splenectomy. In addition to conventional agents such as corticosteroids
      and intravenous immune globulin (IVIg), the role of newer therapies with diverse
      mechanisms of action, such as rituximab, anti-D, and thrombopoietin (TPO)-like
      agents, will be highlighted. When used as either monotherapy or in combination
      with conventional therapeutics, these treatments may offer a more tolerable side
      effect profile and improved clinical benefit compared to existing drugs.

PMID- 16815347
TI  - Human liver slices as an in vitro model to study toxicity-induced hepatic
      stellate cell activation in a multicellular milieu.
AB  - INTRODUCTION: Hepatic stellate cell (HSC) activation is a key event in wound
      healing as well as in fibrosis development in the liver. Previously we developed
      a technique to induce HSC activation in slices from rat liver. Although this
      model provides a physiologic, multicellular milieu that is not present in current
      in vitro models it might still be of limited predictive value for the human
      situation due to species-differences. Therefore, we now aimed to evaluate the
      applicability of human liver slices for the study of HSC activation. METHOD:
      Liver slices (8 mm diameter, 250 microm thickness) were generated from human
      liver tissue and incubated for 3 or 16 h with 0-15 microl of carbon tetrachloride
      (CCl4) after which ATP-content and expression levels of HSC (activation) markers
      was determined. RESULTS: Human liver slices remained viable during incubation as
      shown by constant ATP levels. Incubation with CCl(4) caused a dose-dependent
      decrease in viability and an increase in mRNA expression of the early HSC
      activation markers HSP47 and alphaB-crystallin, but not the late markers for HSC
      activation, alphaSMA and pro-collagen 1a1. Synaptophysin mRNA expression remained
      constant during incubation with or without CCl4, indicating a constant number of
      HSC in the liver slices. CONCLUSION: We developed a technique to induce early
      toxicity-induced HSC activation in human liver slices. This in vitro model
      provides a multicellular, physiologic milieu to study mechanisms underlying
      toxicity-induced HSC activation in human liver tissue.

PMID- 16815348
TI  - Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT
      proBNP.

PMID- 16815349
TI  - Pitfalls, errors and risks of false-positive results in urinary EPO drug tests.

PMID- 16815350
TI  - Altered expression, intracellular distribution and activity of lymphocyte calpain
      II in Duchenne muscular dystrophy.
AB  - BACKGROUND: Calpain II is an calcium-dependent cysteine protease involved in
      essential regulatory or processing functions of the cell, mediated by
      physiological concentrations of Ca(2+). However, in an environment of abnormal
      intracellular calcium as in Duchenne muscular dystrophy (DMD), calpain is
      suggested to cause membrane alterations. METHODS: Twelve individuals with
      dystrophin gene deletion and an equal number of age and sex matched controls were
      chosen for the study. The expression pattern of calpain II (both at RNA and
      protein levels), its cellular location upon activation and its activity in
      lymphocytes were specifically assessed to know if our earlier report of increased
      calpain activity in DMD lymphocytes is a result of de novo synthesis or is due to
      basic defect in calcium handling. RESULTS: We found a significant increase in the
      expression, alteration in calpain II distribution and increased activity of this
      enzyme. CONCLUSION: Membrane abnormalities and altered signaling pathways
      observed in DMD lymphocytes may be due to increased association of calpain II
      onto membrane and cytosol.

PMID- 16815351
TI  - Serum insulin-like growth factor-I measurement in the follow-up of treated
      acromegaly: comparison of four immunoassays.
AB  - BACKGROUND: Measurement of serum insulin-like growth factor I (IGF-I) is
      currently used for the diagnosis and for monitoring treated acromegaly. In this
      work, we have studied the performances of four IGF-1 immunoassays in the follow
      up of acromegaly. METHODS: The study was carried out on 52 sera from 40 patients
      with treated acromegaly. Serum IGF-I was measured with radioimmunoassays from
      Immunotech, DiaSorin and Schering Laboratories and by the chemiluminescent
      automated immunoassay (Advantage) from Nichols. Normal age- and gender-matched
      subjects constituted the reference population for two assays. RESULTS: Deming
      regression and Bland-Altman analyses showed a high correlation with the four
      methods tested. The use of restricted number of age-adjusted controls with the
      Immunotech assay, the DiaSorin assay and the Schering assay induced discordance
      with the Nichols assay in the interpretation of results in treated acromegaly.
      When normal ranges of the Immunotech assay and the DiaSorin assay were defined
      from large number of controls, the frequency of normal IGF-I became similar as
      that obtained with the Nichols assay. CONCLUSION: The four immunoassays display
      suitable analytical performance for serum IGF-I measurement in the follow-up of
      acromegaly. For correct interpretation, IGF-I normal ranges should be defined in
      a large number of age-adjusted healthy subjects.

PMID- 16815352
TI  - Development of an ELISA for myeloperoxidase on microplate: normal reference
      values and effect of temperature on specimen preparation.
AB  - BACKGROUND: Myeloperoxidase (MPO), a leukocyte enzyme, is implicated in both the
      pathogenesis and the progression of atherosclerosis. METHODS: We developed a
      sandwich ELISA on microplate using commercial antibodies for the measurement of
      plasma MPO. RESULTS: The in-house ELISA has a sensitivity of 15 ng/ml. Both
      within-day and between-day imprecision were <10%. The in-house assay was well
      correlated with the commercial kit from Oxis (gamma=0.96). We have established
      normal reference range for MPO for apparently healthy Chinese. No statistical
      difference was found between males and females and the various age groups.
      Because the coating antibodies used by two different kits are different in their
      affinities for MPO, the analysis by the in-house ELISA that was approximately
      three times that of the Oxis kit when testing the same specimens. We found that
      it is necessary to keep the heparinized whole blood on ice before centrifugation
      in order to prevent further release of MPO from the leukocytes at room
      temperature. For the same reason, serum is not recommended for MPO measurement.
      We also found that either pooled human plasma or serum containing MPO can be used
      as calibrators. CONCLUSIONS: We believe that this ELISA for MPO is useful to
      assess risk for inflammation, oxidative stress, nitrosative stress, and for
      predicting cardiac events.

PMID- 16815354
TI  - The US President's Malaria Initiative.

PMID- 16815355
TI  - Funding of patients' groups.

PMID- 16815356
TI  - Assisted reproductive technologies hit all time high.

PMID- 16815358
TI  - The epidemiology of colonialism.

PMID- 16815360
TI  - Transient cerebral arteriopathy in childhood.

PMID- 16815359
TI  - Evolution of hypertensive disease: a revolution in guidelines.

PMID- 16815361
TI  - Measuring malaria drug efficacy and transmission intensity.

PMID- 16815362
TI  - Withdrawal of care in Japan.

PMID- 16815363
TI  - Tony McMichael: a visionary of the environment-health interface.

PMID- 16815364
TI  - Life-threatening complications of the Atkins diet?

PMID- 16815365
TI  - Life-threatening complications of the Atkins diet?

PMID- 16815366
TI  - Life-threatening complications of the Atkins diet?

PMID- 16815367
TI  - How prepared is Europe for pandemic influenza?

PMID- 16815369
TI  - How prepared is Europe for pandemic influenza?

PMID- 16815370
TI  - Activation of coagulation system during air travel.

PMID- 16815371
TI  - Inhaled insulin.

PMID- 16815373
TI  - Autologous bone-marrow stem cells for myocardial infarction.

PMID- 16815374
TI  - Human rights in China.

PMID- 16815375
TI  - Bronchopulmonary dysplasia and intrauterine growth restriction.

PMID- 16815376
TI  - The health-worker migration crisis.

PMID- 16815377
TI  - Relation between age and cardiovascular disease in men and women with diabetes
      compared with non-diabetic people: a population-based retrospective cohort study.
AB  - BACKGROUND: Adults with diabetes are thought to have a high risk of
      cardiovascular disease (CVD), irrespective of their age. The main aim of this
      study was to find out the age at which people with diabetes develop a high risk
      of CVD, as defined by: an event rate equivalent to a 10-year risk of 20% or more;
      or an event rate equivalent to that associated with previous myocardial
      infarction. METHODS: We did a population-based retrospective cohort study using
      provincial health claims to identify all adults with (n=379,003) and
      (n=9,018,082) without diabetes mellitus living in Ontario, Canada, on April 1,
      1994. Individuals were followed up to record CVD events until March 31, 2000.
      FINDINGS: The transition to a high-risk category occurred at a younger age for
      men and women with diabetes than for those without diabetes (mean difference 14.6
      years). For the outcome of acute myocardial infarction (AMI), stroke, or death
      from any cause, diabetic men and women entered the high-risk category at ages
      47.9 and 54.3 years respectively. When we used a broader definition of CVD that
      also included coronary or carotid revascularisation, the ages were 41.3 and 47.7
      years for men and women with diabetes respectively. INTERPRETATION: Diabetes
      confers an equivalent risk to ageing 15 years. However, in general, younger
      people with diabetes (age 40 or younger) do not seem to be at high risk of CVD.
      Age should be taken into account in targeting of risk reduction in people with
      diabetes.

PMID- 16815378
TI  - Incidence of tick-borne relapsing fever in west Africa: longitudinal study.
AB  - BACKGROUND: The ongoing drought in sub-Saharan countries has led to the
      colonisation of west African Savanna by Ornithodoros sonrai; this tick acts as a
      vector for Borrelia crocidurae, which causes tick-borne relapsing fever (TBRF).
      Our aim was to ascertain the incidence of TBRF in west Africa. METHODS: From 1990
      to 2003, we monitored the incidence of TBRF in Dielmo, Senegal, by daily clinical
      surveillance and by blood testing of individuals with a fever. From 2002 to 2005,
      we investigated the presence of O sonrai in 30 villages in Senegal, Mauritania,
      and Mali, and measured by PCR the prevalence of B crocidurae. FINDINGS: The
      average incidence of TBRF over 14 years was 11 per 100 person-years (range from 4
      in 1990 to 25 in 1997). All age-groups presented a high incidence of the disease.
      In addition to relapses, repeated infections in the same individuals were common,
      with some affected by up to six distinct infections during the study period.
      Epidemiological studies indicated that 26 of the 30 studied villages (87%) were
      colonised by the vector tick O sonrai and that the average B crocidurae infection
      rate of the vector was 31%. INTERPRETATION: The incidence of TBRF at the
      community level is the highest described in Africa for any bacterial disease. The
      presence of the vector tick in most villages investigated and its high infection
      rate suggest that TBRF is a common cause of fever in most rural areas of Senegal,
      Mauritania, and Mali.

PMID- 16815379
TI  - What is the contribution of smoking and socioeconomic position to ethnic
      inequalities in mortality in New Zealand?
AB  - BACKGROUND: Mortality rates for Maori are twice those for non-Maori in New
      Zealand. We have assessed the contribution of tobacco smoking and socioeconomic
      position to these inequalities in 45-74-year-old census respondents during 1981
      84 and 1996-99 (2.3 and 2.7 million person-years, respectively). METHODS: We used
      linked census and mortality cohort datasets with measures of socioeconomic
      position (household income, highest educational qualification, car access, labour
      force status, and neighbourhood deprivation) and smoking (never, ex, current). We
      used direct standardisation to adjust for smoking and Poisson regression to
      adjust for socioeconomic position. FINDINGS: The apparent contribution of smoking
      to mortality differences between Maori and non-Maori non-Pacific people was
      greatest for women in 1996-99 (8% reduction in standardised rate difference); it
      had increased from 3% in 1981-84. The corresponding reductions in men were 5% in
      1996-99 and -1% in 1981-84. The apparent contribution of socioeconomic factors to
      mortality differences between Maori and non-Maori non-Pacific was greatest for
      men (39% in 1981-84 and 37% in 1996-99) and increased over time for women (from
      23% in 1981-84 to 32% in 1996-99). INTERPRETATION: Although small, the
      contribution of smoking to ethnic inequalities in mortality increased over time
      and might grow more during the next two decades if differences in smoking between
      ethnic groups continue to increase. Better measurement of socioeconomic position
      (eg, lifecourse measures, asset wealth) might increase the proportion of ethnic
      inequalities attributable to socioeconomic position, perhaps to about half.
      Action to redress socioeconomic gaps and control of tobacco use will both be
      important in reducing ethnic inequalities in health.

PMID- 16815380
TI  - Heart and lung transplantation in children.
AB  - During the past two decades, several advances have resulted in marked improvement
      in medium-term survival for infants and children undergoing heart
      transplantation. Unfortunately, progress has been less dramatic in the field of
      lung and heart-lung transplantation, where there is little evidence of improved
      outcomes. The procedures remain palliative and all transplant recipients are at
      risk for the adverse effects of non-specific immunosuppression, including
      infections, lymphoproliferative disorders, and non-lymphoid malignancies. In
      addition, current immunosuppressive agents have narrow therapeutic windows and
      exhibit a wide array of organ toxicities, posing special challenges for the young
      patient who must endure life-long immunosuppression. New immunosuppressive
      regimens have lowered the rates of acute rejection but appear to have had
      relatively little impact on the incidence of chronic rejection, the principal
      cause of late graft loss. The ultimate goal is to induce a state of donor
      specific tolerance, wherein the recipient will accept the allograft indefinitely
      without the need for long-term immunosuppression. This quest is currently being
      realised in animal models of solid organ transplantation, and offers great hope
      for children undergoing heart and lung transplantation in the future.

PMID- 16815381
TI  - Mitochondrial disease.
AB  - Defects of mitochondrial metabolism cause a wide range of human diseases that
      include examples from all medical subspecialties. This review updates the topic
      of mitochondrial diseases by reviewing the most important recent advances in this
      area. The factors influencing inheritance, maintenance and replication of mtDNA
      are reviewed and the genotype-phenotype of mtDNA disorders has been expanded,
      with new insights into epidemiology, pathogenesis and its role in ageing.
      Recently identified nuclear gene mutations of mitochondrial proteins include
      mutations of frataxin causing Friedreich's ataxia, PINK1, DJ1 causing Parkinson's
      disease and POLG causing infantile mtDNA depletion syndrome, ophthalmoplegia,
      parkinsonism, male subfertility and, in a transgenic mouse model, premature
      senescence. Mitochondrial defects in neurodegenerative diseases include
      Parkinson's, Alzheimer's and Huntington's disease. Improved understanding of
      mtDNA inheritance and mutation penetrance patterns, and novel techniques for
      mtDNA modification offer significant prospects for more accurate genetic
      counselling and effective future therapies.

PMID- 16815382
TI  - Are statins analogues of vitamin D?
AB  - There are many reasons why the dietary-heart-cholesterol hypothesis should be
      questioned, and why statins might be acting in some other way to reduce the risk
      of coronary heart disease. Here, I propose that rather than being cholesterol
      lowering drugs per se, statins act as vitamin D analogues, and explain why. This
      proposition is based on published observations that the unexpected and
      unexplained clinical benefits produced by statins have also been shown to be
      properties of vitamin D. It seems likely that statins activate vitamin D
      receptors.

PMID- 16815383
TI  - Transmission of mitochondrial DNA disorders: possibilities for the future.

PMID- 16815384
TI  - Haemolysis, elevated liver enzymes, and thrombocytopenia in a 34-year-old
      pregnant woman.

PMID- 16815386
TI  - Negative regulation of Egfr/Ras pathway by Ultrabithorax during haltere
      development in Drosophila.
AB  - In Drosophila, wings and halteres are the dorsal appendages of the second and
      third thoracic segments, respectively. In the third thoracic segment, homeotic
      selector gene Ultrabithorax (Ubx) suppresses wing development to mediate haltere
      development (E.B. Lewis, 1978. A gene complex controlling segmentation in
      Drosophila. Nature 276, 565-570). Halteres lack stout sensory bristles of the
      wing margin and veins that reticulate the wing blade. Furthermore, wing and
      haltere epithelia differ in the size, shape, spacing and number of cuticular
      hairs. The differential development of wing and haltere, thus, constitutes a good
      genetic system to study cell fate determination. Here, we report that down
      regulation of Egfr/Ras pathway is critical for haltere fate specification: over
      expression of positive components of this pathway causes significant haltere-to
      wing transformations. RNA in situ, immunohistochemistry, and epistasis genetic
      experiments suggest that Ubx negatively regulates the expression of the ligand
      vein as well as the receptor Egf-r to down-regulate the signaling pathway.
      Electromobility shift assays further suggest that Egf-r is a potential direct
      target of Ubx. These results and other recent findings suggest that homeotic
      genes may regulate cell fate determination by directly regulating few steps at
      the top of the hierarchy of selected signal transduction pathways.

PMID- 16815385
TI  - Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell
      lineage regulates sequential steps of osteoblast maturation.
AB  - Mutations in fibroblast growth factor receptors (Fgfrs) 1-3 cause skeletal
      disease syndromes in humans. Although these Fgfrs are expressed at various stages
      of chondrocyte and osteoblast development, their function in specific skeletal
      cell types is poorly understood. Using conditional inactivation of Fgfr1 in osteo
      chondrocyte progenitor cells and in differentiated osteoblasts, we provide
      evidence that FGFR1 signaling is important for different stages of osteoblast
      maturation. Examination of osteogenic markers showed that inactivation of FGFR1
      in osteo-chondro-progenitor cells delayed osteoblast differentiation, but that
      inactivation of FGFR1 in differentiated osteoblasts accelerated differentiation.
      In vitro osteoblast cultures recapitulated the in vivo effect of FGFR1 on stage
      specific osteoblast maturation. In immature osteoblasts, FGFR1 deficiency
      increased proliferation and delayed differentiation and matrix mineralization,
      whereas in differentiated osteoblasts, FGFR1 deficiency enhanced mineralization.
      Furthermore, FGFR1 deficiency in differentiated osteoblasts resulted in increased
      expression of Fgfr3, a molecule that regulates the activity of differentiated
      osteoblasts. Mice lacking Fgfr1, either in progenitor cells or in differentiated
      osteoblasts, showed increased bone mass as adults. These data demonstrate that
      signaling through FGFR1 in osteoblasts is necessary to maintain the balance
      between bone formation and remodeling through a direct effect on osteoblast
      maturation.

PMID- 16815387
TI  - In vitro maturation of human oocytes in a follicle-mimicking three-dimensional
      coculture.
AB  - OBJECTIVE: To verify the hypothesis that a three-dimensional, follicle-mimicking
      structure enhances in vitro maturation yields without hormonal supplementation in
      an in vitro maturation program. DESIGN: Feasibility study; 204 anonymous denuded
      germinal vesicles retrieved from gonadotropin-treated women were cultured for 48
      hours without hormonal supplementation in microdrop culture or in a three
      dimensional coculture with granulosa cells in a barium alginate membrane.
      SETTING: An assisted reproduction center in Italy. PATIENT(S): One hundred twenty
      two informed women. INTERVENTION(S): Germinal vesicles retrieved after ovarian
      stimulation were denuded and cultured without hormonal supplementation in
      microdrop culture or in a three-dimensional coculture with granulosa cells
      enclosed in the core of a barium alginate capsule. MAIN OUTCOME MEASURE(S):
      Oocyte maturation and morphological investigation of follicle-mimicking
      structures. RESULT(S): Statistically significantly higher oocyte maturation
      yields were obtained by using the three-dimensional coculture system enclosed in
      a barium alginate membrane (after 48 hours: coculture, 90.3%; microdrop, 52.0%;
      odds ratio, 8.51). Morphological investigation indicated that after 48 hours of
      coculture, the decumulated oocyte appeared to be surrounded by a pseudocumulus
      structure that lies on the inner surface of the alginate membrane and protrudes
      toward the capsule's lumen. CONCLUSION(S): The maturation yield of cocultured
      oocytes is eightfold higher than that achieved with a microdrop maturation
      technique, making a higher number of gametes available for IVF programs.
      Stereomicroscopic morphological survey indicates a reassembly of granulosa cells
      surrounding oocyte zona, mimicking an antral cumulus oophorus.

PMID- 16815388
TI  - Differential expression of genes in eutopic and ectopic endometrium from patients
      with ovarian endometriosis.
AB  - OBJECTIVE: To investigate whether genes that had been found to be differentially
      expressed in deep-infiltrating endometriosis and matched eutopic endometrium in
      our previous complementary DNA microarray study also are differentially expressed
      in ovarian endometriosis and matched eutopic endometrium. DESIGN: Prospective
      study. SETTING: University hospital in France. PATIENT(S): Patients with ovarian
      endometriosis. INTERVENTION(S): During surgery, paired samples of tissue
      representing ovarian endometriosis and eutopic endometrium were obtained from 12
      patients. MAIN OUTCOME MEASURE(S): Expression levels of messenger RNA for heat
      shock protein 90 alpha (HSP90A), chicken ovalbumin upstream promoter
      transcription factor 2 (COUP-TF2), prostaglandin E(2) receptor subtype EP3
      (PGE(2)EP3), tyrosine kinase receptor B (TrKB), and 17beta-hydroxysteroid
      dehydrogenase type 2 (17betaHSD2; epithelial cells) and of platelet-derived
      growth factor receptor alpha (PDGFRA), protein kinase C beta 1 (PKCbeta1), Janus
      kinase 1 (JAK1), mitogen-activated protein kinase kinase (MKK7), Sprouty2, mu
      opioid receptor (MOR), and 5HTT (stromal cells) from ovarian endometriosis and
      matched eutopic endometrium were determined by using laser capture
      microdissection and real-time reverse-transcription polymerase chain reaction (RT
      PCR) techniques. RESULT(S): Expression of PDGFRA, PKCbeta1, JAK1, HSP90A, COUP
      TF2, MOR, and 17betaHSD2 was significantly higher in ovarian endometriosis than
      in eutopic endometrium, whereas that of Sprouty2 and PGE(2)EP3 was significantly
      lower. There was no significant difference in mitochondrial RNA expression of MKK
      7, TrKB, and 5HTT. CONCLUSION(S): Ovarian endometriosis might share several
      common molecules with deep-infiltrating endometriosis that act to sustain
      endometriotic lesions, whereas molecules involved in local endocrine control
      might be different between these two types of endometriosis.

PMID- 16815389
TI  - Chronic 17beta-estradiol pretreatment and ischemia-induced hippocampal
      degeneration and memory impairments: a 6-month survival study.
AB  - Exogenous administration of estrogen has been shown to significantly reduce
      ischemia-induced neuronal degeneration. However, the long-term impact of such
      treatment on neuronal protection and functional recovery remain largely unknown.
      The present study assessed the effects of a 15-day pretreatment with 17beta
      estradiol on memory deficits and neuronal damage up to 6 months following a 10
      min global ischemia in rats. Four groups of ovariectomized female rats [sham
      operated and ischemic rats receiving a 15-day pretreatment of either the vehicle
      or 17beta-estradiol (100 microg/kg)] were tested. The 8-arm radial maze and
      object recognition tests served to evaluate the impact of 17beta-estradiol
      treatment on ischemia-induced spatial and recognition memory impairments,
      respectively. Testing in the radial maze was initiated at two distinct time
      intervals following reperfusion (7 and 120 days) to evaluate changes in memory
      functions over time. Our findings revealed long-lasting neuroprotective effects
      of 17beta-estradiol treatment on hippocampal CA1 pyramidal cells in
      ovariectomized ischemic rats (43.5% greater neuronal survival than observed in
      vehicle-treated ischemic animals). Importantly, this neuronal protection
      translated into significant improvements of recognition and spatial memory
      functions in estradiol-treated ischemic rats.

PMID- 16815391
TI  - Excessive volume of trauma workload out of hours: Is it really true.

PMID- 16815392
TI  - Fracture-separation of the distal humeral epiphysis. Long-term follow-up of five
      cases.
AB  - Fracture-separation of the distal humeral epiphysis is a rare injury described in
      young children. The diagnosis is often difficult because most of the ossification
      centre are not visible. We report a long-term follow-up study of five cases,
      evaluated after an average of 38 years. At the time of fracture, all the patients
      were more than 3 years old. Three patients had been treated with overhead
      traction, closed reduction and immobilisation in a long-arm plaster cast, one
      patient with closed reduction and immobilisation and another one, initially not
      diagnosed, had been treated after 2 weeks with only immobilisation in a long-arm
      plaster cast. Cubitus varus deformity was observed in one of the five patients.
      In the remaining four cases the cubitus was less valgus than the opposite side.
      No patient complained of any functional disability even though in two of them,
      one treated late and another one who had an inadequate reduction, radiographic
      signs of degenerative arthritis were present. We believe that the amount of
      displacement of the fragments, the quality of the reduction and the age at the
      time of fracture are important factors influencing the development of cubitus
      varus deformity.

PMID- 16815393
TI  - Should the tibia be reamed with nailing?

PMID- 16815394
TI  - Mortality and serum urea and electrolytes on admission for hip fracture patients.
AB  - OBJECTIVE: To assess the relationship between pre-operative serum urea and
      electrolyte concentrations and mortality in patients with hip fractures requiring
      surgery. METHODS: A prospective observational study of 2963 consecutive patients
      admitted to a single trauma unit with a hip fracture, treated operatively.
      RESULTS: The 30-day mortality for patients with low and normal urea
      concentrations was 6.9%. The 30-day mortality for patients with raised urea
      concentrations was almost double (11.5%). A raised admission serum urea
      concentration was an independent predictor for mortality at 30 days, 90 days, 1
      year and 2 years. Mortality was significantly increased in patients admitted
      with: raised or low serum sodium, raised serum potassium and raised serum
      creatinine. CONCLUSION: Mortality is high following hip fracture. Patients
      admitted with a raised serum urea are at increased risk of death at all time
      intervals analysed up to and including 2 years. This group of patients may
      require a separate care pathway that provides more intensive management of fluid
      and electrolyte balance.

PMID- 16815395
TI  - Topical beta-adrenergic blockers and glaucoma: a heart-stopping association?

PMID- 16815396
TI  - Open-angle glaucoma and cardiovascular mortality: the Blue Mountains Eye Study.
AB  - PURPOSE: To evaluate the association between open-angle glaucoma (termed
      glaucoma) and 9-year mortality in an older population-based cohort. DESIGN:
      Population-based cohort. PARTICIPANTS: Three thousand six hundred fifty-four
      persons aged 49 to 97 years (82.4% of the eligible population), residents of the
      Blue Mountains, west of Sydney, Australia. METHODS: At baseline (1992-1994),
      glaucoma was diagnosed from congruous typical glaucomatous visual field changes
      (full-threshold fields) and optic disc cupping (stereo-optic disc photography).
      Demographic information from baseline participants was matched with the
      Australian National Death Index data (December 2001) to obtain the number and
      causes of deaths. Cox proportional hazards regression analysis, controlling for
      age, male gender, diabetes, hypertension, heart disease, stroke, use of oral beta
      blockers, current smoking history, alcohol use, myopia, and nuclear cataract were
      performed to assess hazard ratios for cardiovascular mortality. Adjustments for
      all-cause mortality also included history of cancer. MAIN OUTCOME MEASURES:
      Cardiovascular and all-cause mortality. RESULTS: At baseline, glaucoma was
      diagnosed in 108 participants (3.0%). Of 873 deaths (23.9%) before January, 2002,
      312 people (8.5%) died of cardiovascular events. The age-standardized all-cause
      mortality was 24.3% in persons with and 23.8% in those without glaucoma, whereas
      cardiovascular mortality was 14.6% in persons with and 8.4% in those without
      glaucoma. After multivariate adjustment, those with glaucoma had a nonsignificant
      increased risk of cardiovascular death (relative risk [RR], 1.46; 95% confidence
      interval [CI], 0.95-2.23). Increased cardiovascular mortality was observed mainly
      in glaucoma patients aged <75 years (RR, 2.78; 95% CI, 1.20-6.47). Further
      stratified analyses showed that cardiovascular mortality was higher among those
      with previously diagnosed glaucoma (RR, 1.85; 95% CI, 1.12-3.04), particularly in
      those also treated with topical timolol (RR, 2.14; 95% CI, 1.18-3.89).
      CONCLUSIONS: Findings from the Blue Mountains Eye Study demonstrate an increased
      cardiovascular mortality in persons with previously diagnosed glaucoma. There was
      a suggestion of higher cardiovascular mortality in glaucoma patients using
      topical timolol that merits further study.

PMID- 16815397
TI  - Topical beta-blockers are not associated with an increased risk of treatment for
      depression.
AB  - PURPOSE: To investigate the effect of topical beta-blockers on the prevalence of
      depression among glaucoma patients. DESIGN: Retrospective observational
      population-based cohort study. PARTICIPANTS: We reviewed the electronic medical
      records of all the members in a district of the largest health maintenance
      organization in Israel (Central District of Clalit Health Services) who were
      older than 20 years (317,469 members). METHODS: We documented all antiglaucoma
      prescriptions (n = 274,023) and all antidepressant prescriptions (n = 16,948)
      filled by glaucoma patients in the district between January 1, 2001 and December
      31, 2003. We included only those patients who filled at least 6 consecutive
      antiglaucoma prescriptions at least once every 2 months (n = 6597; 5846 [88.6%]
      were treated with topical beta-blockers). Depressed patients were defined as
      patients that filled at least four prescriptions for antidepressants during the
      study period (n= 810, 12.3% of all glaucoma patients). MAIN OUTCOME MEASURE:
      Relationship of topical beta-blocker use and prevalence of depression among
      glaucoma patients. RESULTS: No significant demographic differences were noted
      between glaucoma patients treated and not treated with topical beta-blockers. Of
      those treated and not treated with beta-blockers, 12.2% (12.7% after age
      adjustment) and 12.7%, respectively, were also receiving drug therapy for
      depression (P = 0.7, chi-square test). With stratification by age, treatment with
      topical beta-blockers did not influence the prevalence of depression in any age
      group. Logistic regression analysis revealed a significant effect of age, place
      of birth, and gender on the prevalence of depression, but the prevalence of use
      of topical beta-blockers had no significant effect. CONCLUSIONS: Use of topical
      beta-blockers by glaucoma patients does not appear to increase the risk of
      depression in this population.

PMID- 16815398
TI  - Long-term outcomes in fellow eyes after acute primary angle closure in the
      contralateral eye.
AB  - PURPOSE: To determine the long-term outcome of the contralateral eye in Asian
      persons with a unilateral attack of acute primary angle closure (APAC). DESIGN:
      Cross-sectional observational case series. PARTICIPANTS: Seventy-nine individuals
      who were examined from 4 to 10 years after a unilateral episode of APAC at 2
      Singapore hospitals. METHODS: All subjects underwent a complete eye examination.
      The optic discs were graded clinically and photographically for the presence of
      glaucomatous optic neuropathy, and automated visual field tests were assessed for
      damage. All visual fields and optic nerve photographs (when available) underwent
      a second evaluation by a masked glaucoma specialist, who assessed whether the
      changes were compatible with glaucoma. MAIN OUTCOME MEASURES: Glaucomatous optic
      neuropathy, intraocular pressure (IOP), and visual impairment (defined as best
      corrected visual acuity of worse than 6/12). RESULTS: Ninety of 138 eligible
      patients (65.2%) with APAC were examined, 79 with unilateral attacks. Subjects
      were predominantly Chinese (n = 68; 86%). There were 54 females (68%), and mean
      age was 68.5+/-8.9 years (standard deviation) at the time of APAC, with a mean
      duration of 6.3+/-1.5 years from the time of the APAC episode to the study
      examination. The contralateral eyes of 7 patients (8.9%) had definite or probable
      glaucoma, 2 of whom were felt to have glaucoma in that eye at the time of the
      attack. Three eyes had markedly cupped optic discs (cup-to-disc ratio > or =
      0.9). Thirteen eyes (16.9%) had best-corrected vision worse than 6/12, due to
      cataract in almost half the cases. Only 1 eye had vision < 6/60, the cause of
      which was corneal decompensation. One other patient had only a central island
      remaining with vision of 6/12. Mean IOP of the study participants was 15.7+/-4.7
      mmHg, with 6 subjects (7.6%) having undergone trabeculectomy. CONCLUSIONS:
      Definite or probable glaucoma was present at the time of diagnosis in 2 (2.5%)
      fellow eyes and developed in an additional 5 (6.5%) with a mean follow-up of 6
      years. More than 80% of this cohort retained good vision in the contralateral
      eye, in contrast to the eye that underwent APAC. Unoperated cataract accounted
      for most of the visual impairment in this group.

PMID- 16815399
TI  - Diagnostic sensitivity of fast blue-yellow and standard automated perimetry in
      early glaucoma: a comparison between different test programs.
AB  - PURPOSE: To compare the ability of Fast Swedish interactive threshold algorithm
      (SITA) short-wavelength automated perimetry (SWAP), lengthier full-threshold
      SWAP, and standard automated perimetry (SAP) using the SITA Fast program to
      detect early glaucomatous visual field loss. DESIGN: Cross-sectional prospective
      study of perimetric diagnostic sensitivity as defined by reference limits
      determined in the same healthy participants for all 3 test programs.
      PARTICIPANTS: One hundred one patients with ocular hypertension, or suspect or
      early manifest glaucoma. METHODS: One eye of each patient was tested with 2 blue
      yellow perimetric programs: the SITA and full-threshold SWAP and the SAP SITA
      Fast program. MAIN OUTCOME MEASURES: Glaucomatous visual field loss, defined as
      number of significantly depressed test point locations or the number of clusters
      of such test points. RESULTS: No significant difference in number of
      significantly depressed test point locations between the 3 programs could be
      detected, neither at the P<5% limit nor at the P<2% limit. The difference in
      number of points depressed below the fifth percentile was 0.5 between full
      threshold SWAP and SITA SWAP, 1.09 between full-threshold SWAP and SAP, and 1.04
      between SITA SWAP and SAP. The number of eyes showing clusters of significantly
      depressed points also was similar with the 3 test programs: full-threshold SWAP
      identified clusters in 66 eyes, SITA SWAP identified clusters in 67 eyes, and
      SITA Fast SAP identified clusters in 65 eyes. Average test time was 12.0 minutes
      using full-threshold SWAP, 4.1 minutes with SITA SWAP, and 3.5 with SITA Fast.
      CONCLUSIONS: The SITA SWAP identified at least as much glaucomatous visual field
      loss as the older full-threshold SWAP, although test time was considerably
      reduced. Conventional SAP using SITA Fast was not significantly less sensitive
      than either of the 2 SWAP programs.

PMID- 16815400
TI  - Ocular trauma in a rural population of southern India: the Andhra Pradesh Eye
      Disease Study.
AB  - OBJECTIVE: To determine the prevalence of ocular trauma and proportion of
      blindness and visual impairment due to ocular trauma in a rural population of
      southern India. DESIGN: Population-based cross-sectional epidemiological study.
      PARTICIPANTS: A total of 7771 subjects of all ages, representative of the rural
      population of Andhra Pradesh. METHODS: The subjects underwent a detailed
      interview and comprehensive ocular evaluation as part of the population-based
      Andhra Pradesh Eye Disease Study. MAIN OUTCOME: An eye was considered to be blind
      due to trauma if best-corrected distance visual acuity was worse than 6/60 and
      the cause was attributed to ocular trauma. RESULTS: A total of 824 (10.6%)
      subjects gave a history of ocular trauma in either eye, including 76 (1.0%)
      persons reporting trauma in both eyes. The overall age- and gender-adjusted
      prevalence of history of eye injury in this rural population was 7.5% (95%
      confidence interval [CI], 7.0%-8.1%). Men were more likely to have an eye injury
      than women (odds ratio [OR], 2.1 [95% CI, 1.8-2.5]). After adjusting for gender
      and other demographic factors, ocular trauma was significantly more frequent
      among laborers (OR, 1.5 [95% CI, 1.2-1.7]) when compared with other occupational
      groups. After adjusting for gender, injury with vegetable matter such as a thorn,
      branch of a tree, plant secretion, etc. (n = 373 [45.3%]) was the major cause of
      trauma reported in this population. The majority of the eye injuries occurred at
      the workplace (n = 461 [55.9%]), followed by home (n = 179 [21.7%]). The majority
      of those affected (n = 806 [97.8%]) did not wear any eye protection at the time
      of trauma. A significant proportion (n = 307 [43.1%]) of subjects who sought
      treatment for an eye injury went to an ophthalmologist. Trauma was responsible
      for unilateral blindness in 39 subjects, an age- and gender-adjusted prevalence
      of 0.6% (95% CI, 0.4%-0.8%). CONCLUSIONS: Most ocular injuries in this rural
      population occurred at the workplace, suggesting the need to explore workplace
      strategies to minimize ocular trauma as a priority. Eye care programs targeting
      high-risk ocular trauma groups may need to consider ocular trauma as a priority
      in eye health awareness strategies to reduce blindness due to trauma.

PMID- 16815401
TI  - Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a
      systematic review.
AB  - TOPIC: What is the evidence for efficacy of dietary and/or supplemental omega-3
      fatty acids in preventing age-related macular degeneration (AMD)? CLINICAL
      RELEVANCE: Age-related macular degeneraion is the leading cause of blindness and
      vision impairment in persons older than 50 years living in North America. There
      is no cure for AMD, and treatment does not usually restore vision but only
      prevents disease progression to a modest degree. omega-3 fatty acids are
      considered potentially important antioxidants and are being considered as an arm
      of the Age-Related Eye Disease Study II clinical trial. METHODS/LITERATURE
      REVIEWED: Keywords were searched in Medline, Pre-Medline, Embase, and the
      Cochrane Library on Ovid. There was no restriction on the year or language of
      publication. RESULTS: There were 6 observational studies found, but the specific
      outcomes, exposures, and covariates studied all varied greatly. CONCLUSION: There
      is some clinical evidence for protection of AMD from omega-3 fatty acids.
      However, the results are not consistent. Hence, our conclusion is that this issue
      is neither clearly supported nor refuted by the present world literature. This is
      an intriguing and extremely important question but needs further study first with
      prospective cohort designs and, if positive, randomized clinical trials.

PMID- 16815402
TI  - Insulinlike growth factor I affects ocular development: a study of untreated and
      treated patients with Laron syndrome.
AB  - OBJECTIVE: To evaluate the ocular dimensions in patients with primary growth
      hormone receptor insensitivity (Laron syndrome [LS]) and to study the effect of
      supplemental insulinlike growth factor I (IGF-I) on ocular growth. DESIGN:
      Retrospective case series. PARTICIPANTS: Twelve patients with LS, 8 untreated (LS
      group) and 4 treated (LS-T group) with supplemental IGF-I, and 30 healthy
      controls. METHODS: Ocular dimensions and refraction were measured, and a full
      ophthalmologic examination was performed. MAIN OUTCOME MEASURES: Differences in
      the average ocular dimension data among IGF-I-treated patients, untreated ones,
      and controls. RESULTS: The average axial length of eyes in the LS group was 21.94
      mm (standard deviation [SD], 0.81). Corresponding values for the LS-T and control
      group eyes were 22.53 mm (SD, 1.74) and 23.20 mm (SD, 1.35) respectively. The
      average anterior chamber depth of eyes in the LS group was 2.55 mm (SD, 0.26).
      Corresponding values for eyes in the LS-T and control groups were 3.48 mm (SD,
      0.09) and 3.84 mm (SD, 0.16) respectively. The average lens thickness of eyes in
      the LS group was 4.56 mm (SD, 0.36). Corresponding values for the LS-T and
      control groups were 3.77 mm (SD, 0.23) and 3.51 mm (SD, 0.25), respectively. The
      average corneal curvature of eyes in the LS group was 46.9 diopters (D) (SD,
      2.32). Corresponding values for the LS-T and control groups were 47.6 D (SD,
      2.83) and 44.4 D (SD, 1.5), respectively. CONCLUSIONS: Insulinlike growth factor
      I seems to be an important regulator of ocular growth as documented in patients
      with primary growth hormone insensitivity. The mechanism of this observation
      should be investigated further.

PMID- 16815403
TI  - Superior tarsectomy augments super-maximum levator resection in correction of
      severe blepharoptosis with poor levator function.
AB  - OBJECTIVE: To determine if a superior tarsectomy improves the ptosis corrective
      ability of the super maximum levator resection in cases of severe blepharoptosis
      with poor levator function (less than 5 mm). DESIGN: Retrospective, consecutive
      case series. PARTICIPANTS: Patients who underwent super maximum levator resection
      with (8 eyelids) or without superior tarsectomy (10 eyelids) at one institution.
      METHODS: Chart review of patients who underwent super maximum levator resection
      with or without superior tarsectomy. Data regarding eyelid position, surgical
      outcome, and postoperative complications were evaluated. MAIN OUTCOME MEASURES:
      Margin reflex distance-1 (distance [mm] between corneal light reflex and upper
      eyelid margin), bilateral eyelid symmetry, and postoperative complications.
      RESULTS: A statistically significant improvement in ptosis correction was
      demonstrated when integrating the superior tarsectomy with the super maximum
      levator resection (P = 0.029). In addition, the superior tarsectomy significantly
      decreased the incidence of undercorrection (margin reflex distance-1 values less
      than 2.0 mm) compared with the super-maximum levator resection alone (12.5% vs.
      70%; P = 0.023). Improved postoperative eyelid symmetry within 1.0 and 1.5 mm was
      demonstrated in cases treated by the superior tarsectomy. Postoperative
      complications were similar in both treatments. CONCLUSIONS: The super maximum
      levator resection combined with superior tarsectomy can correct severely ptotic
      eyelids with Berke levator function ranging from 3 to 4.5 mm.

PMID- 16815404
TI  - Orbital decompression as an alternative management strategy for patients with
      benign tumors located at the orbital apex.
AB  - PURPOSE: Tumors located in the intraconal portion of the orbital apex, especially
      those inferior to the optic nerve, can be difficult to access surgically,
      carrying a significant risk of ocular morbidity. The purpose of this study was to
      investigate outcomes in 5 patients with benign-appearing but symptomatic tumors
      located in the intraconal portion of the orbital apex in which orbital
      decompression was performed as an alternative management strategy to resection.
      DESIGN: Retrospective interventional case series. PARTICIPANTS: Five patients
      were diagnosed with a compressive optic neuropathy secondary to a benign
      appearing tumor at the orbital apex. INTERVENTION: Each patient underwent
      surgical decompression of the affected orbit. None of the patients had the tumor
      biopsied or resected. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA),
      pupillary responses, visual fields (VFs), color vision, and orbital imaging.
      RESULTS: Each of the patients demonstrated improvement in visual function, as
      measured by VA, VFs, and, in some cases, color vision. One patient required a
      second orbital decompression for recurrent optic neuropathy 4 years after the
      initial decompression. Complications included ptosis and enophthalmos in 2
      patients and diplopia in the extreme right gaze in 1 patient. CONCLUSIONS:
      Orbital decompression is a therapeutic option for patients with compressive optic
      neuropathies from benign orbital apex tumors, offering potential improvement in
      optic nerve function while sparing morbidity from attempts at surgical resection.

PMID- 16815405
TI  - Lessons learned from difficult or unsuccessful cannulations of the superior
      ophthalmic vein in the treatment of cavernous sinus dural fistulas.
AB  - OBJECTIVE: Retrograde cannulation of the superior ophthalmic vein (SOV) is an
      important route for embolization of cavernous sinus dural fistulas (CDF). We
      present our experience with technically difficult cases in which it was not
      possible to isolate or cannulate this vein. DESIGN: Retrospective,
      noncomparative, interventional case series. PATIENTS: All patients diagnosed with
      dural CDF at the University of California Los Angeles Medical Center between
      January, 1993, and July, 2005, and who were treated with embolization via the
      SOV. METHODS: The clinical records of all patients were reviewed. MAIN OUTCOME
      MEASURES: Patient demographics, clinical presentation, and surgical findings.
      RESULTS: Of 91 patients diagnosed with CDF during the study period, 25 patients
      (16 females, 9 males; mean age, 59 years) were treated with embolization via the
      SOV. In 6 of them (24%; 4 women and 2 men; mean age, 67 years), there were
      significant difficulties in cannulation of the SOV or in successful closure of
      the fistula with this approach. Three patients had a fragile or a very small vein
      that could not be cannulated, and 1 of the 3 also had a large, posteriorly
      located varix that bled extensively on attempted cannulation. In 2 other
      patients, the anterior segment of the SOV was clotted and the catheter could not
      be threaded. In 1 patient, an inferior location of the supraorbital vein resulted
      in difficulties in correct identification of the SOV. CONCLUSIONS: Although the
      SOV is a useful route for CDF embolization, the presence of fragile or clotted
      veins can preclude successful cannulation. Deeper orbital dissections carry a
      higher risk of uncontrolled bleeding and should be avoided, especially in older
      patients with fragile veins and those with recently diagnosed high-flow fistulas.

PMID- 16815406
TI  - Scleral buckling versus primary vitrectomy.

PMID- 16815408
TI  - Scleral buckling versus primary vitrectomy.

PMID- 16815409
TI  - Scleral buckling versus primary vitrectomy.

PMID- 16815411
TI  - Ciliary body edema.

PMID- 16815414
TI  - Vision screening.

PMID- 16815415
TI  - Accommodation affected by warming?

PMID- 16815418
TI  - Topographically guided LASIK.

PMID- 16815419
TI  - Cataract after laser iridotomy.

PMID- 16815420
TI  - Orbital ischemia.

PMID- 16815422
TI  - IOP variation.

PMID- 16815423
TI  - IOP variation.

PMID- 16815425
TI  - Retention in overloaded columns, an experimental approach.
AB  - Employing a micro-bore silica capillary coated with Carbowax 20 M, the dependence
      of chromatographic retention upon operative variables was studied surpassing the
      sample capacity of the column. Solution thermodynamics in the non-linear range of
      the absorption isotherm of n-alkanes on poly(ethylene oxide) were analyzed
      interpreting the experimental data through a retention equation deduced in a
      preceding theoretical work. At 120 degrees C, and pressures up to 11 bar abs,
      deviations from the ideal-gas behavior are found to be negligible, either for the
      fluid dynamics of the carrier-gas, or the thermodynamics of solution of the n
      alkanes. Within the experimental error, for all practical purposes the mobile
      phase can be treated as an ideal gas. This constraint allows studying a solute
      molecule placed in an environment ranging from solvent monomers only, to a
      mixture of varying composition of solvent and solute, avoiding effects from
      significant interactions in the gas phase. In the experimental conditions
      explored, the absorption isotherm can be represented by taking only two-terms of
      its power series development.

PMID- 16815426
TI  - Theoretical aspects of retention in overloaded columns.
AB  - Issues regarding the concentration dependent solute distributions in overloaded
      chromatographic columns are discussed. Geometric simplicity of wall-coated
      capillary columns is taken as a reference and the discussion is developed using
      the example of the absorption isotherm of a solute having more affinity for
      itself than for the stationary phase. A retention function is deduced solving the
      equation of motion for the peak maximum, making some approximations. By means of
      this expression, the applicability of capillary gas chromatography (GC) as a
      technique for obtaining information on the sorption isotherm is analyzed.

PMID- 16815427
TI  - Chromatography as Levy stochastic process.
AB  - The Stochastic Theory of Chromatography has been revised in light of some of the
      most relevant Levy's findings in Theory of Probability, including the so-called
      Levy's distance, the characteristic function and the theory of infinitesimally
      divisible distributions. These concepts represent the key to exploit and
      understand, at a molecular basis, phenomena typical of chromatographic
      separations under linear conditions, such as peak tailing and splitting. In
      particular, Levy's distance has been used to quantify the degree of convergence
      of real peaks towards an ideal Gaussian shape; the characteristic function
      properties, introduced by Levy to deal with the problem of the addition of
      independent random variables, have been employed to solve a wide variety of
      chromatographic models (including adsorption on heterogeneous surfaces) and to
      interpret mobile phase dispersion from a probabilistic point of view. Finally,
      Levy's studies concerning infinitesimally divisible distributions have allowed to
      introduce in the stochastic description of chromatography, effects associated to
      dispersion in mobile phase. It has been demonstrated that, according to Levy's
      canonical representation of stochastic processes, the basis of chromatography is
      a mobile phase Poisson Process. Represented as a Levy's process, the microscopic
      probabilistic model of chromatography permits the establishment of a connection
      between single-molecule properties and their statistical fluctuations and shapes
      of real chromatographic peaks allowing, at the same time, for the constitution of
      a link between different branches of physical sciences.

PMID- 16815428
TI  - Fractionation of red wine polyphenols by solid-phase extraction and liquid
      chromatography.
AB  - A systematic method for separation of aged red wine polyphenols into various
      distinct fractions using combined techniques of solid-phase extraction and liquid
      chromatography was proposed. The aged red wine polyphenols were separated into
      various distinct fractions including phenolic acid fraction, monomer flavanol
      fraction, oligomer procyanidin fraction, anthocyanin and its pyruvic acid
      derivative fraction, free or non-colored proanthocyanidin fraction, fraction of
      direct condensation products between anthocyanins and proanthocyanidins and
      fraction of other pigmented complexes. The phenolic composition of each fraction
      was verified by HPLC with diode array detection (HPLC-DAD), thiolysis, vanillin
      assay, HPLC coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS)
      and multi-stage MS fragment analysis. For the first time, anthocyanins and their
      pyruvic derivatives were separated from other phenolic compounds, while free or
      non-pigmented polymer proanthocyanidins from other pigmented complexes. The
      fractionation method would be of particular interest in further studying the
      detailed composition of polymeric polyphenols in red wine.

PMID- 16815429
TI  - Gas chromatographic retention data of wax esters.
AB  - Higher wax esters within the range of C24 to C44 (205 standards) were analyzed by
      means of gas chromatography and Kovats indexes (I) and reduced Kovats indexes
      (RKI) were calculated. The dependences of these retention data on number of
      carbon atoms and on number and position of double bonds in acid and in alcohol
      moieties of esters were plotted.

PMID- 16815430
TI  - Nanoscale electrostatic actuators in liquid electrolytes.
AB  - Equilibrium and energy analyses were performed for an electrostatic actuator
      consisting of two plane parallel electrodes, operated using DC voltages,
      separated by a liquid electrolyte. One electrode is fixed, and the other
      electrode is connected to a spring and is free to move. The mechanical
      equilibrium includes the spring force, the van der Waals force, and the
      electrochemical force as given by the solution of the linearized Poisson
      Boltzmann equation. The electrode separation is determined as a function of the
      applied potential, the natural (i.e., zeta) potential, the Debeye length, the
      initial electrode separation, the spring constant, and the Hamaker constant. The
      actuator exhibits the classical "pull-in" instability. The natural potential
      increases the critical applied potential but does not significantly affect the
      critical separation. For zero natural potential, the spring constant does not
      affect the critical separation. Ratios of the maximum spring energy, the maximum
      van der Waals energy, and the maximum electrochemical energy were plotted as
      functions of the Hamaker constant and the initial electrode separation.

PMID- 16815431
TI  - The distribution of oestrogen receptors in normal, hyperplastic and neoplastic
      canine prostate, as demonstrated immunohistochemically.
AB  - The role of oestrogens and their receptors (ERs) in prostatic growth and
      differentiation and in the progression of prostatic carcinoma has been well
      investigated in human medicine. In dogs, however, available reports on the
      expression of ERs in normal, hyperplastic or neoplastic prostates are few and
      controversial, or completely lacking. Three normal, three hyperplastic and nine
      neoplastic canine prostates were examined histologically, and
      immunohistochemically with a polyclonal antibody directed against human ERs.
      Evaluation of the percentage of immunolabelled cells was performed by digital
      image analysis. The study showed that ERs were expressed in the nuclei of
      epithelial and stromal cells in normal, hyperplastic and neoplastic prostates.
      All nuclei in normal and hyperplastic prostates were strongly and homogeneously
      immunolabelled by the antibody used. However, the percentages of immunolabelled
      nuclei in the nine prostatic carcinomas were greatly reduced, ranging from 36.34%
      to 66.73%. The severe loss of ER expression in canine prostatic carcinomas may
      account for the relative lack of differentiation of these tumours in the dog.

PMID- 16815432
TI  - Captopril prevents myosin light chain phosphatase isoform switching to preserve
      normal cGMP-mediated vasodilatation.
AB  - Congestive heart failure (CHF) is characterized by abnormal vasoconstriction and
      an impairment in nitric oxide (NO)-mediated vasodilatation. We have previously
      demonstrated that the decrease in sensitivity to NO lies at least partially at
      the level of the smooth muscle and is due to a reduction in the relative
      expression of the leucine zipper positive (LZ(+)) isoform of the myosin targeting
      subunit (MYPT1) of myosin light chain phosphatase. We hypothesized that since the
      attenuated vasodilatory response to NO in CHF has been shown to be secondary to
      an increased activity of the renin-angiotensin system, angiotensin converting
      enzyme (ACE) inhibition could affect MYPT1 isoform expression. To test this
      hypothesis, a rat myocardial infarction (MI) model of CHF was used; following
      left coronary artery ligation, rats were divided into control and captopril
      treated groups. A third group of rats was given prazosin for 4 weeks. In the
      untreated control group, left ventricular function (LVF) was reduced at 2 weeks
      post-MI and remained at this level. Captopril treatment attenuated the fall in
      LVF. In the control aorta and iliac artery, the expression of the LZ(+) MYPT1
      isoform fell 44-52% between 2 and 4 weeks post-MI, whereas in animals treated
      with captopril, MYPT1 isoform expression did not change. A decrease in the
      sensitivity to cGMP-mediated smooth muscle relaxation occurred coincident with
      the decrease in LZ(+) MYPT1 expression. The change in LZ(+) MYPT1 expression was
      not due to the decrease in afterload, as prazosin therapy produced an improvement
      in LVF but did not increase the relative expression of LZ(+) MYPT1 isoform. These
      data suggest that ACE inhibition, unique from pure afterload reduction, prevents
      MYPT1 isoform switching, which would preserve normal flow, or NO-mediated
      vasodilatation.

PMID- 16815433
TI  - Global changes in gene expression during cardiac hypertrophy: a new direction of
      cardiac signaling research.

PMID- 16815434
TI  - Calcitriol modulation of cardiac contractile performance via protein kinase C.
AB  - Vitamin D(3) deficiency enhances cardiac contraction in experimental studies, yet
      paradoxically this deficiency is linked to congestive heart failure in humans.
      Activated vitamin D(3) (1alpha,25-dihydroxyvitamin D(3)) or calcitriol, decreases
      peak force and activates protein kinase C (PKC) in isolated perfused hearts.
      However, the direct influence of this hormone on adult cardiac myocyte
      contractile function is not well understood. Our aim is to investigate whether
      1alpha,25-dihydroxyvitamin D(3) acutely modulates contractile function via PKC
      activation in adult rat cardiac myocytes. Sarcomere shortening and re-lengthening
      were measured in electrically stimulated myocytes isolated from adult rat hearts,
      and the vitamin D(3) response (10(-10) to 10(-7) M) was compared to shortening
      observed under basal conditions. Maximum changes in sarcomere shortening and
      relaxation were observed with 10(-9) M 1alpha,25-dihydroxyvitamin D(3). This dose
      decreased peak shortening, and accelerated contraction and relaxation rates
      within 5 min of administration, and changes in the Ca(2+) transient contributed
      to the peak shortening and relaxation effects. The PKC inhibitor, bis
      indolylmaleimide (500 nM) largely blocked the acute influence of the most potent
      dose (10(-9) M) on contractile function. While peak shortening and shortening
      rate returned to baseline within 30 min, there was a sustained acceleration of
      relaxation that continued over 60 min. Phosphorylation of the Ca(2+) regulatory
      proteins, phospholamban, and cardiac troponin I correlated with the accelerated
      relaxation observed in response to acute application of 1alpha,25
      dihydroxyvitamin D(3). Accelerated relaxation continued to be observed after
      chronic addition of 1alpha,25-dihydroxyvitamin D(3) (e.g. 2 days), yet this
      sustained increase in relaxation was not associated with increased
      phosphorylation of phospholamban or troponin I. These results provide evidence
      that 1alpha,25-dihydroxyvitamin D(3) directly modulates adult myocyte contractile
      function, and protein kinase C plays an important signaling role in the acute
      response. Phosphorylation of key Ca(2+) regulatory proteins by this kinase
      contributes to the enhanced relaxation observed in response to acute, but not
      chronic calcitriol.

PMID- 16815435
TI  - Where is behavioural ecology going?
AB  - Since the 1990s, behavioural ecologists have largely abandoned some traditional
      areas of interest, such as optimal foraging, but many long-standing challenges
      remain. Moreover, the core strengths of behavioural ecology, including the use of
      simple adaptive models to investigate complex biological phenomena, have now been
      applied to new puzzles outside behaviour. But this strategy comes at a cost.
      Replication across studies is rare and there have been few tests of the
      underlying genetic assumptions of adaptive models. Here, I attempt to identify
      the key outstanding questions in behavioural ecology and suggest that researchers
      must make greater use of model organisms and evolutionary genetics in order to
      make substantial progress on these topics.

PMID- 16815436
TI  - What have exotic plant invasions taught us over the past 20 years?
AB  - Invasive organisms have become a focal interest in ecology, owing not only to the
      tremendous destruction that they can cause, but also because we do not yet
      understand fully how they change from being minor components of their native
      communities to dominant components of invaded communities. Here, we discuss our
      perceptions of how the study of exotic plant species has contributed to the
      changing face of ecology over the past 20 years. Research on invasive organisms
      has promoted synthetic efforts between fields that have historically operated in
      isolation. Most importantly, the study of invasions has resulted in significant
      intellectual shifts in the way that old paradigms are perceived by ecologists and
      have led us into new and uncharted territory.

PMID- 16815437
TI  - A future for models and data in environmental science.
AB  - Together, graphical models and the Bayesian paradigm provide powerful new tools
      that promise to change the way that environmental science is done. The capacity
      to merge theory with mechanistic understanding and empirical evidence, to
      assimilate diverse sources of information and to accommodate complexity will
      transform the collection and interpretation of data. As we discuss here, we
      specifically expect a shift from a focus on simple experiments with inflexible
      design and selection among models that embrace parts of processes to a synthesis
      of integrated process models. With this potential come new challenges, including
      some that are specific and technical and others that are general and will involve
      reexamination of the role of inference and prediction.

PMID- 16815438
TI  - Network structure and the biology of populations.
AB  - A scientific growth area in recent years has been the study of networks of
      interacting entities within a population, including species in food webs, human
      or other animals transmitting infection, proteins in cells, cells in organisms
      (e.g. neuronal networks), the internet and the World Wide Web. Here, I review
      some of the differing network patterns that arise in theory and in practice, with
      an emphasis on their dynamical implications, particularly for resistance to
      deliberate or accidental disturbance. I offer caveats and opinionated comment
      about some excesses of enthusiasm and suggest some areas where these network
      ideas might find further application.

PMID- 16815439
TI  - How close are we to a predictive science of the biosphere?
AB  - In just 20 years, the field of biosphere-atmosphere interactions has gone from a
      nascent discipline to a central area of modern climate change research. The
      development of terrestrial biosphere models that predict the responses of
      ecosystems to climate and increasing CO2 levels has highlighted several
      mechanisms by which changes in ecosystem composition and function might alter
      regional and global climate. However, results from empirical studies suggest that
      ecosystem responses can differ markedly from the predictions of terrestrial
      biosphere models. As I discuss here, the challenge now is to connect terrestrial
      biosphere models to empirical ecosystem measurements. Only by systematically
      evaluating the predictions of terrestrial biosphere models against suites of
      ecosystem observations and experiments measurements will a true predictive
      science of the biosphere be achieved.

PMID- 16815440
TI  - Adrm1, a putative cell adhesion regulating protein, is a novel proteasome
      associated factor.
AB  - We have identified Adrm1 as a novel component of the regulatory ATPase complex of
      the 26 S proteasome: Adrm1 was precipitated with an antibody to proteasomes and
      vice versa. Adrm1 co-migrated with proteasomes on gel-filtration chromatography
      and non-denaturing polyacrylamide gel electrophoresis. Adrm1 has been described
      as an interferon-gamma-inducible, heavily glycosylated membrane protein of 110
      kDa. However, we found Adrm1 in mouse tissues only as a 42 kDa peptide,
      corresponding to the mass of the non-glycosylated peptide chain, and it could not
      be induced in HeLa cells with interferon. Adrm1 was present almost exclusively in
      soluble 26 S proteasomes, albeit a small fraction was membrane-associated, like
      proteasomes. Adrm1 was found in cells in amounts equimolar with S6a, a 26 S
      proteasome subunit. HeLa cells contain no pool of free Adrm1 but recombinant
      Adrm1 could bind to pre-existing 26 S proteasomes in cell extracts. Adrm1 may be
      distantly related to the yeast proteasome subunit Rpn13, mutants of which are
      reported to display no obvious phenotype. Accordingly, knock-down of Adrm1 in
      HeLa cells had no effect on the amount of proteasomes, or on degradation of bulk
      cell protein, or accumulation of polyubiquitinylated proteins. This indicates
      that Adrm1 has a specialised role in proteasome function.

PMID- 16815441
TI  - Specificity of the initial collapse in the folding of the cold shock protein.
AB  - The two-state folding reaction of the cold shock protein from Bacillus
      caldolyticus (Bc-Csp) is preceded by a rapid chain collapse. A fast shortening of
      intra-protein distances was revealed by Forster resonance energy transfer (FRET)
      measurements with protein variants that carried individual pairs of donor and
      acceptor chromophores at various positions along the polypeptide chain. Here we
      investigated the specificity of this rapid compaction. Energy transfer
      experiments that probed the stretching of strand beta2 and the close approach
      between the strands beta1 and beta2 revealed that the beta1-beta2 hairpin is
      barely formed in the collapsed form, although it is native-like in the folding
      transition state of Bc-Csp. The time course of the collapse could not be resolved
      by pressure or temperature jump experiments, indicating that the collapsed and
      extended forms are not separated by an energy barrier. The co-solute (NH4)2SO4
      stabilizes both native Bc-Csp and the collapsed form, which suggests that the
      large hydrated SO4(2-) ions are excluded from the surface of the collapsed form
      in a similar fashion as they are excluded from folded Bc-Csp. Ethylene glycol
      increases the stability of proteins because it is excluded preferentially from
      the backbone, which is accessible in the unfolded state. The collapsed form of Bc
      Csp resembles the unfolded form in its interaction with ethylene glycol,
      suggesting that in the collapsed form the backbone is still accessible to water
      and small molecules. Our results thus rule out that the collapsed form is a
      folding intermediate with native-like chain topology. It is better described as a
      mixture of compact conformations that belong to the unfolded state ensemble.
      However, some of its structural elements are reminiscent of the native protein.

PMID- 16815442
TI  - Variations in the unstructured C-terminal tail of interferons contribute to
      differential receptor binding and biological activity.
AB  - Type I interferons (IFNs) elicit antiviral, antiproliferative and
      immunomodulatory properties in cells. All of them bind to the same receptor
      proteins, IFNAR1 and IFNAR2, with different affinities. While the 13 known
      IFNalphas are highly conserved, the C-terminal unstructured tail was found to
      have large variation in its net charge, from neutral to +4. This led us to
      speculate that the tail may have a role in modulation of the IFN biological
      activity, through fine-tuning the binding to IFNAR2. To evaluate this hypothesis,
      we replaced the tail of IFNalpha2 with that of IFNalpha8 and IFNbeta tails, or
      deleted the last five residues of this segment. Mutations to the more positively
      charged tail of IFNalpha8 resulted in a 20-fold higher affinity to IFNAR2, which
      results in a higher antiviral and antiproliferative activity. Double and multiple
      mutant cycle analysis placed the tail near a negatively charged loop on IFNAR2,
      comprising of residues Glu 132-134. Deleting the tail resulted in only twofold
      reduction in binding compared to the wild-type. Next, we modeled the location of
      the tail using a two-step procedure: first we generated 200 models of the tail
      docked on IFNAR2 using HADDOCK, second the models were scored according to the
      fit between experimentally determined rates of association of nine mutant
      complexes, and their calculated rates using the PARE software. From the results
      we suggest that the unstructured tail of IFNalpha is gaining a specific structure
      in the bound state, binding to a groove below the 132-134 loop in IFNAR2.

PMID- 16815444
TI  - Population of on-pathway intermediates in the folding of ubiquitin.
AB  - The role that intermediate states play in protein folding is the subject of
      intense investigation and in the case of ubiquitin has been controversial. We
      present fluorescence-detected kinetic data derived from single and double mixing
      stopped-flow experiments to show that the F45W mutant of ubiquitin (WT*), a well
      studied single-domain protein and most recently regarded as a simple two-state
      system, folds via on-pathway intermediates. To account for the discrepancy we
      observe between equilibrium and kinetic stabilities and m-values, we show that
      the polypeptide chain undergoes rapid collapse to an intermediate whose presence
      we infer from a fast lag phase in interrupted refolding experiments. Double-jump
      kinetic experiments identify two direct folding phases that are not associated
      with slow isomerisation reactions in the unfolded state. These two phases are
      explained by kinetic partitioning which allows molecules to reach the native
      state from the collapsed state via two possible competing routes, which we
      further examine using two destabilised ubiquitin mutants. Interrupted refolding
      experiments allow us to observe the formation and decay of an intermediate along
      one of these pathways. A plausible model for the folding pathway of ubiquitin is
      presented that demonstrates that obligatory intermediates and/or chain collapse
      are important events in restricting the conformational search for the native
      state of ubiquitin.

PMID- 16815443
TI  - Structure of cytochrome c6A, a novel dithio-cytochrome of Arabidopsis thaliana,
      and its reactivity with plastocyanin: implications for function.
AB  - Cytochrome c6A is a unique dithio-cytochrome present in land plants and some
      green algae. Its sequence and occurrence in the thylakoid lumen suggest that it
      is derived from cytochrome c6, which functions in photosynthetic electron
      transfer between the cytochrome b6f complex and photosystem I. Its known
      properties, however, and a strong indication that the disulfide group is not
      purely structural, indicate that it has a different, unidentified function. To
      help in the elucidation of this function the crystal structure of cytochrome c6A
      from Arabidopsis thaliana has been determined in the two redox states of the heme
      group, at resolutions of 1.2 A (ferric) and 1.4 A (ferrous). These two structures
      were virtually identical, leading to the functionally important conclusion that
      the heme and disulfide groups do not communicate by conformational change. They
      also show, however, that electron transfer between the reduced disulfide and the
      heme is feasible. We therefore suggest that the role of cytochrome c6A is to use
      its disulfide group to oxidize dithiol/disulfide groups of other proteins of the
      thylakoid lumen, followed by internal electron transfer from the dithiol to the
      heme, and re-oxidation of the heme by another thylakoid oxidant. Consistent with
      this model, we found a rapid electron transfer between ferro-cytochrome c6A and
      plastocyanin, with a second-order rate constant, k2=1.2 x 10(7) M(-1) s(-1).

PMID- 16815445
TI  - The art of the abstract.

PMID- 16815446
TI  - Gender differences in the Swedish driving-license test.
AB  - INTRODUCTION: Male drivers between 18-24 years are involved in many more motor
      vehicle accidents than female drivers in Sweden. Is there also a gender
      difference in test performance in the Swedish driving-license tests? Is it a real
      difference or do any of the items display differential item functioning (DIF)
      with respect to gender or educational background? METHOD: Two random samples of
      test-takers' performance on the Swedish theory driving-license test were examined
      with descriptive and inference statistics. RESULTS: Female test-takers performed
      better than male test-takers on the theory test, which is a real difference since
      no items displayed DIF with respect to gender. There was no gender difference in
      the practical test. The gender difference in the theory test could not be fully
      explained by differences in educational background. CONCLUSIONS: Although
      everyone who passes the driving-license test has fulfilled the goals stated in
      the curriculum, it is possible that the gender differences in the theory test are
      consistent over time, and therefore might be one factor that explains why male
      drivers are over-represented in traffic accidents. IMPACT ON INDUSTRY: Gender
      differences appear persistent over time. Therefore, by improving male test
      takers' result on the test may lead to positive effects on the male test takers
      future driving career.

PMID- 16815447
TI  - Driver hand-held cellular phone use: a four-year analysis.
AB  - INTRODUCTION: The use of hand-held cellular (mobile) phones while driving has
      stirred more debate, passion, and research than perhaps any other traffic safety
      issue in the past several years. There is ample research showing that the use of
      either hand-held or hands-free cellular phones can lead to unsafe driving
      patterns. Whether or not these performance deficits increase the risk of crash is
      difficult to establish, but recent studies are beginning to suggest that cellular
      phone use elevates crash risk. METHODS: The purpose of this study was to assess
      changes in the rate of hand-held cellular phone use by motor-vehicle drivers on a
      statewide level in Michigan. This study presents the results of 13 statewide
      surveys of cellular phone use over a 4-year period. Hand-held cellular phone use
      data were collected through direct observation while vehicles were stopped at
      intersections and freeway exit ramps. Data were weighted to be representative of
      all drivers traveling during daylight hours in Michigan. RESULTS: The study found
      that driver hand-held cellular phone use has more than doubled between 2001 and
      2005, from 2.7% to 5.8%. This change represents an average increase of 0.78
      percentage points per year. The 5.8% use rate observed in 2005 means that at any
      given daylight hour, around 36,550 drivers were conversing on cellular phones
      while driving on Michigan roadways. The trend line fitted to these data predicts
      that by the year 2010, driver hand-held cellular phone use will be around 8.6%,
      or 55,000 drivers at any given daylight hour. CONCLUSIONS: These results make it
      clear that cellular phone use while driving will continue to be an important
      traffic safety issue, and highlight the importance of continued attempts to
      generate new ways of alleviating this potential hazard.

PMID- 16815448
TI  - The porcine remnant kidney model of chronic renal insufficiency.
AB  - BACKGROUND: The purpose of the present study was to develop and characterize a
      porcine model of chronic renal insufficiency created by renal artery
      embolization. METHODS: The model was created using 42 castrated juvenile male
      pigs (7-8 months old) in two parts (pilot (N = 10) group, definitive (N = 26)
      group, and control group (N = 6). In the pilot group, the embolization procedure
      was optimized with respect to the size of polyvinyl acrylide (PVA) particles,
      coils, and amount of kidney embolized. The animals were followed serially for 4
      weeks after the embolization procedure to determine the renal function and
      hypertensive response. In the definitive group, these results were extended to
      later time points and a left total nephrectomy and a right partial nephrectomy
      (remnant) were performed and these animals were followed for 28 to 84 days.
      RESULTS: The kidney function after the embolization was characterized by acute
      deterioration in renal function, followed by improvement, and "stable" chronic
      renal insufficiency with statistically significant elevation in creatinine and
      BUN being observed until day 42. The mean arterial blood pressure remained
      significantly elevated until day 7 after which it began to decrease to pre
      embolization value. The remnant kidney developed fibrosis in the
      tublointerstitial compartment as it hypertrophied and increased its weight which
      remained significantly elevated after embolization. CONCLUSIONS: A reproducible
      remnant kidney model of chronic renal insufficiency in pigs was developed. In
      this model, stable renal insufficiency develops by 4 weeks that lasts until 12
      weeks.

PMID- 16815449
TI  - Early hemodynamic and renal effects of hemorrhagic shock resuscitation with
      lactated Ringer's solution, hydroxyethyl starch, and hypertonic saline with or
      without 6% dextran-70.
AB  - BACKGROUND: Considering the renal effects of fluid resuscitation in hemorrhaged
      patients, the choice of fluid has been a source of controversy. In a model of
      hemorrhagic shock, we studied the early hemodynamic and renal effects of fluid
      resuscitation with lactated Ringer's (LR), 6% hydroxyethyl starch (HES), and 7.5%
      hypertonic saline (HS) with or without 6% dextran-70 (HSD). MATERIALS AND
      METHODS: Forty-eight dogs were anesthetized and submitted to splenectomy. An
      estimated 40% blood volume was removed to maintain mean arterial pressure (MAP)
      at 40 mm Hg for 30 min. The dogs were divided into four groups: LR, in a 3:1
      ratio to removed blood volume; HS, 6 mL kg(-1); HSD, 6 mL kg(-1); and HES in a
      1:1 ratio to removed blood volume. Hemodynamics and renal function were studied
      during shock and 5, 60, and 120 min after fluid replacement. RESULTS: Shock
      treatment increased MAP similarly in all groups. At 5 min, cardiac filling
      pressures and cardiac performance indexes were higher for LR and HES but, after
      120 min, there were no differences among groups. Renal blood flow and glomerular
      filtration rate (GFR) were higher in LR at 60 min but GFR returned to baseline
      values in all groups at 120 min. Diuresis was higher for LR at 5 min and for LR
      and HES at 60 min. There were no differences among groups in renal variables 120
      min after treatment. CONCLUSIONS: Despite the immediate differences in
      hemodynamic responses, the low-volume resuscitation fluids, HS and HSD, are
      equally effective to LR and HES in restoring renal performance 120 min after
      hemorrhagic shock treatment.

PMID- 16815450
TI  - Role of steroid administration to reduce inflammation after thoracotomy in a rat
      surgical stress model.
AB  - BACKGROUND: Unilateral lung surgical insult can lead to bilateral pulmonary
      inflammation after transthoracic esophagectomy for esophageal cancer. An
      inflammatory response of the cytokine network induced by surgical stress followed
      by neutrophil sequestration is the major mechanism involved in these
      complications. We examined modulation of the inflammatory cytokine and neutrophil
      sequestration by preoperative steroid administration in a rat thoracotomy model.
      METHODS: Adult male rats were subjected to right thoracotomy with pulmonary
      compression in the surgical stress model. In the another surgical stress model,
      10 mg/kg of methylprednisolone (MP) was administered 1 h before the operation
      intraperitoneally, and peri-operative biological effects of steroid
      administration to neutrophil sequestration and cytokine-induced neutrophil
      chemoattractant (CINC) as an inflammatory cytokine were examined. Sham-operated
      animals were subjected to intubation only. RESULTS: Surgical insult to the
      unilateral lung increased local CINC concentration followed by an increase in
      neutrophil sequestration, wet-to-dry weight ratio in bilateral lungs and systemic
      CINC concentration. Pre-treatment with methylprednisolone reduced CINC
      concentration as well as neutrophil sequestration and wet-to-dry weight ratio of
      both lungs. CONCLUSIONS: These data suggest that inflammatory changes induced by
      the unilateral operative procedure occur in both lungs through local inflammatory
      response. Pre-operative methylprednisolone administration down-regulates cytokine
      release and neutrophil sequestration, preventing lung edema, and possibly may act
      as a prophylactic treatment against acute lung injury caused by a so-called
      "second attack" theory.

PMID- 16815453
TI  - Emerging natural threats and the deliberate use of biological agents.
AB  - Over the past several years there has been an increasing awareness and interest
      by the medical community, the media, and government at all levels regarding the
      need to plan for and defend against biological weapons. This article offers an
      overview of various new and emerging natural biological threats.

PMID- 16815451
TI  - Differential gene expression in patients genetically predisposed to pancreatic
      cancer.
AB  - BACKGROUND: Nearly 10% of all pancreatic cancer (PCA) results from genetic
      predisposition. Although abnormalities in sporadic PCA have been described,
      little is known about the genetics of heritable PCA. The purpose of this study
      was to identify novel genes expressed in patients with a presumed genetic
      predisposition or "familial" PCA. PATIENTS AND METHODS: We defined "familial" PCA
      as patients having one or more first-degree relatives with biopsy-proven
      adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment
      procedure, representational difference analysis (RDA), pancreatic tumor cDNA was
      reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and
      compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene
      fragments were identified and confirmed to be overexpressed in familial PCA by
      comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine
      tumors, and 3 chronic pancreatitis tissues were screened to determine the
      specificity of these genes. RESULTS: Sequence analysis revealed several sequences
      of unknown significance and six genes previously described in
      neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3
      sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell
      lines and pancreatic tissue types showed varying degrees of specificity for
      familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA.
      CONCLUSIONS: The pattern of frequency in all screened tissue suggests that these
      genes are associated with conditions that produce significant desmoplastic
      responses and are difficult to differentiate from chronic inflammatory processes.
      Apolipoprotein A4 is preferentially expressed in familial patients, suggesting
      that the importance of fatty acid synthesis in carcinogenesis be investigated
      further.

PMID- 16815454
TI  - Clinical laboratories, the select agent program, and biological surety
      (biosurety).
AB  - The threat of bioterrorism has led to increased concerns over the availability of
      biological select agents and toxins (BSAT). Congress has implemented several
      public laws that have led to the development of federal regulations by the
      Centers for Disease Control and Prevention (CDC) and the US Department of
      Agriculture. The CDC regulation 42 CFR 73 has a direct impact on all clinical
      laboratories that may at some time identify BSAT in a clinical specimen. The
      Department of Defense has imposed a more stringent layer of regulation called
      biological surety (biosurety) on top of the requirements of 42 CFR 73 for
      military laboratories that possess BSAT. However,42 CFR 73 falls into the
      framework of biosurety. Both sets of regulations have four pillars (safety,
      physical security, agent account-ability, and personnel reliability) that are
      built on a foundation of training and covered by a roof of management (operations
      and plans).

PMID- 16815455
TI  - Medical strategies to handle mass casualties from the use of biological weapons.
AB  - This article reviews the definitions of biological weapons and mass casualties.
      In addition, it discusses the main operational and logistical issues of import in
      the medical management of mass casualties from the use of biological weapons.
      Strategies for medical management of specific biologic agents also are
      highlighted.

PMID- 16815456
TI  - Clinical and pathologic differential diagnosis of selected potential bioterrorism
      agents of interest to pediatric health care providers.
AB  - The early recognition of potential bioterrorism agents has been of increasing
      concern in recent years. The Centers for Disease Control and Prevention has
      categorized and listed biological terrorism agents. Although any or all of the
      highest risk biological agents (including inhalation anthrax, pneumonic plague,
      smallpox, tularemia, botulism, and viral hemorrhagic fevers) can be seen in the
      pediatric patient, several agents might closely resemble--at least in their
      initial stages-some of the more common childhood illnesses. The awareness of
      these similarities and, more importantly,their differences, are critical for all
      health care professionals. Selected examples of some typical childhood illnesses
      are presented and then compared with three of the most virulent biological agents
      (smallpox, anthrax and plague) that might be used in a bioterrorism attack.

PMID- 16815457
TI  - Viral hemorrhagic fevers.
AB  - A taxonomically diverse set of single-stranded ribonucleic acid(ssRNA) viruses
      from four diverse viral families Arenaviridae,Bunyaviridae, Filoviridae, and
      Flaviviridae cause an acute systemic febrile syndrome called viral hemorrhagic
      fever (VHF). The syndrome produces combinations of prostration, malaise,
      increased vascular permeability, and coagulation maladies. In severe illness,VHF
      may include generalized bleeding but the bleeding does not typically constitute a
      life-threatening loss of blood volume. To a certain extent, it is a sign of
      damage to the vascular endothelium and is an indicator of disease severity in
      specific target organs. Although the viruses that cause hemorrhagic fever (HF)
      can productively replicate in endothelial cells, much of the disease pathology
      including impairment to the vascular system is thought to result primarily from
      the release of a variety of mediators from virus-infected cells, such as
      monocytes and macrophages that subsequently alter vascular function and trigger
      the coagulation disorders that epitomize these infections. While significant
      progress has been made over the last several years in dissecting out the
      molecular biology and pathogenesis of the HF viruses, there are currently no
      vaccines or drugs licensed available for most of the VHFs.

PMID- 16815458
TI  - Fungi as bioweapons.
AB  - Fungi cause disease directly by infection or indirectly through mycotoxins. Fungi
      that are used as weapons might be targeted against humans, livestock, or crops.
      Humans and animals encounter fungi and mycotoxins through inhalation, ingestion,
      and contact with skin and mucous membranes. Effective fungal bioweapons would
      require the ability to cause significant destruction and a means of delivery to
      target populations or farms. Effective counter measures against fungal bioweapons
      would be able to prevent or treat this damage. This article describes several
      potential biological warfare or bioterrorism fungal species and mycotoxins in
      regard to their biology, epidemiology, potential for weaponization, and the
      clinical features, prevention, and treatment of the diseases that they cause.

PMID- 16815459
TI  - Toxins: bacterial and marine toxins.
AB  - The term toxin refers in a specific way to a toxic substance of biologic origin;
      that is, a true toxin is a poison produced by a living organism. The purpose of
      this article is to review some of the most potentially dangerous toxins of
      concern today. Mechanisms of action, routes of exposure, diagnostic tools, and
      treatment recommendations are addressed. In addition, current therapeutic uses
      for certain toxins are discussed.

PMID- 16815460
TI  - Bioregulators as prototypic nontraditional threat agents.
AB  - Bioregulators are naturally occurring organic compounds that regulate a multitude
      of biologic processes. Under natural circumstances, bioregulators are synthesized
      in minute quantities in a variety of living organisms and are essential for
      physiologic homeostasis. In the wrong hands, these compounds have the capability
      to be used as nontraditional threat agents that are covered by the prohibitions
      of the Chemical Weapons Convention and the Biological and Toxin Weapons
      Convention. Unlike traditional biowarfare/bioterrorism agents that have a latency
      period of hours to days,the onset of action of bioregulators may occur within
      minutes after host exposure. Concerns regarding the potential misuse of
      bioregulators for nefarious purposes relate to the ability of these
      nontraditional agents to induce profound physiologic effects.

PMID- 16815461
TI  - Clinicopathologic aspects of animal and zoonotic diseases of bioterrorism.
AB  - We live in an era of emerging infectious diseases and the threat of bioterrorism.
      Most of the infectious agents of modern concern, from plague to avian influenza
      H5N1, are zoonotic diseases: infectious agents that reside in quiet animal
      reservoir cycles that are transmitted occasionally to humans. The public health,
      health care, and veterinary communities have an enormous challenge in the early
      recognition, reporting, treatment, and prevention of zoonotic diseases. An
      intimate understanding of the natural ecology, geographic distribution, clinical
      signs, lesions, and diagnosis of these diseases is essential for the early
      recognition and control of these diseases.

PMID- 16815462
TI  - Modulating radiation resistance: Insights based on defenses against reactive
      oxygen species in the radioresistant bacterium Deinococcus radiodurans.
AB  - The classical dogma of radiation biology asserts that the cytotoxic effects of
      ionizing radiation (IR) are principally the result of DNA damage. Yet many
      organisms that encode a complement of DNA repair functions are killed by IR doses
      that cause little DNA damage. Instead, proteins likely are the first major class
      of molecules damaged by IR. This article presents a new perspective on extreme IR
      resistance in the eubacterium Deinococcus radiodurans, reevaluates the role of
      superoxide (02*-) ions in IR toxicity, and speculates on potential strategies for
      controlling resistance in prokaryotes and eukaryotes based on scavenging IR
      induced 02*-.

PMID- 16815463
TI  - Immunologic aspects of select agents.
AB  - We are on the cusp of exciting new developments in vaccine biology. The use of
      DNA constructs allows virtually unlimited access to previously inaccessible
      organisms. Next-generation adjuvants will boost innate and acquired immunity, and
      will provide protection from infection with any potential biowarfare organism. We
      are limited only by our imaginations in the construction of a protective
      armamentarium.

PMID- 16815464
TI  - Anatomic laboratory and forensic aspects of biological threat agents.
AB  - Anatomic pathology of surgical and cytologic samples and forensic autopsies is a
      critical component of our defense against biological terrorism. In many
      instances, rapid, valuable diagnosis may be obtained by the proper immediate use
      of the anatomic pathology laboratory. Included in this field is the work of
      medical examiners and coroners, who are essential public health partners for
      terrorism preparedness and response. The investigation of sudden, suspicious,
      violent, unattended, and unexplained deaths may provide the first clue to a
      deliberate biological attack. Medicolegal autopsies are essential to making
      organism-specific diagnoses in deaths caused by biological terrorism.

PMID- 16815466
TI  - Myeloradiculitis caused by Cryptococcus neoformans infection in a patient with
      ulcerative colitis: a neuropathological study.
AB  - Meningitis is the most common feature of cryptococcal infection of the nervous
      system. We herein describe the case of a 48-year-old man with fulminant
      cryptococcal myeloradiculitis, whose initial symptoms were impotence, dysuria and
      weakness of the lower extremities. He had been administered prednisolone and
      azathioprine for 7years for ulcerative colitis before onset of myeloradiculitis.
      He finally developed meningoencephalitis and died 2 months after onset despite
      treatment with amphotericin B and flucytosine. Post-mortem examination revealed
      numerous infiltrations of cryptococci in the spinal roots as well as in the
      meninges and subarachnoid space. Inflammatory cells and cryptococci had
      infiltrated the vessel walls in the spinal cord, and this was accompanied by
      necrotizing myelopathy. Myeloradiculitis is rare in cryptococcal infection, and
      this is the first case report to demonstrate direct cryptococcal infection in the
      spinal roots. Cryptococcal infection should be considered while managing
      myeloradiculopathy of unknown etiology, especially in immunocompromised patients.

PMID- 16815465
TI  - MRI studies of spinal visceral larva migrans syndrome.
AB  - We report serial MR findings in four patients with myelitis caused by visceral
      larva migrans syndrome due to Toxocara canis or Ascaris suum infection. MR
      imaging revealed spinal cord swelling with or without gadolinium enhancement in
      three patients. T2-weighted images showed high signal intensities preferentially
      located in both lateral and posterior columns. Antihelmintic and corticosteroid
      treatment yielded improvement in neurologic deficits and spinal lesions. However,
      one patient with T. canis infection relapsed associated with reappearance of MRI
      abnormalities.

PMID- 16815467
TI  - A shift of paradigm: from noradrenergic to dopaminergic modulation of learning?
AB  - d-Amphetamine coupled with behavioral training has been effective for improving
      functional recovery after stroke. d-amphetamine acts on multiple brain
      transmitter systems, but the recovery enhancing effect has been attributed to its
      noradrenergic actions. Another potent modulator of learning is dopamine, which
      may also enhance stroke recovery in humans. Based on data from previous studies
      of our group, we compared the learning enhancing effects of d-amphetamine with a
      more selective dopaminergic substance (levodopa) in identical protocols. Using a
      prospective, randomized, double-blind, placebo-controlled design, we had taught
      60 male healthy subjects a miniature lexicon of 50 concrete nouns over the course
      of five consecutive training days using an associative learning principle.
      Subjects had received either d-amphetamine (0.25 mg/kg), levodopa/carbidopa
      (fixed dose of 100/25 mg), or placebo 90 min prior to training on each of the 5
      days. Novel word learning was significantly enhanced in both the d-amphetamine
      and levodopa groups as compared to the placebo group. The learning superiority
      was maintained at the two re-assessments (1 week and 1 month post training). Both
      d-amphetamine and levodopa are thus potent drugs in enhancing learning in humans.
      We here discuss why the efficiency of both d-amphetamine and levodopa may be
      related to dopaminergic rather than noradrenergic actions.

PMID- 16815469
TI  - Perinatal risk factors for neonatal intracerebral hemorrhage in preterm infants.
AB  - OBJECTIVE: To investigate the perinatal factors related to neonatal intracerebral
      hemorrhage (ICH) and possibly to define obstetric and perinatal risk factors.
      STUDY DESIGN: All medical records of women who delivered in the period from 1
      January 1991 to 1 January 2000 were reviewed for intracerebral hemorrhages in
      infants born between 24 and 34 weeks of gestation and treated in the postnatal
      period. Sixty infants with ICH (Group I) and 60 infants without ICH (Group II,
      matched controls) were determined for comparison. Obstetrical parameters and risk
      factors and perinatal outcome parameters were evaluated and statistically
      analyzed. RESULTS: Neonatal intracerebral hemorrhage prevalence was 0.8% (60/7635
      births). Betamethasone administration was significantly less in Group I than in
      Group II (27% versus 46%). Although Doppler-sonography of the middle cerebral
      artery was performed in a minority of the cases, it showed a significant tendency
      of lower resistance indices (brain sparing) in the intracerebral hemorrhage group
      (66.7% versus 21.1%). Postnatally, infants with intracerebral hemorrhage showed a
      significantly more often umbilical arterial acidosis (18% versus 10%), a greater
      base deficit, lower median 5 min Apgar scores (6 and 8, respectively for Groups I
      and II), and a lower thrombocyte count (Group I 190,000 +/- 76,000 microl(-1),
      and Group II 227,000 +/- 96,000 microl(-1)). Infants in Group I were more often
      (93% versus 76%) and longer (26.7 +/- 30.5 days versus 15.4 +/- 11.7 days)
      dependent on ventilatory support than infants in Group II. Mortality rate in
      Group I (35%) was significantly higher compared to Group II (17%). CONCLUSIONS:
      Antenatal Doppler sonography in predicting intracerebral hemorrhage in preterm
      infants should be investigated in large scale prospective studies. Postnatal low
      pH-values (pH < 7.1) and a base deficit of more than -16 mmol/L in the umbilical
      artery, low Apgar scores and thrombocytopenia are associated with a neonatal
      intracerebral hemorrhage and prophylaxis with corticosteroids reduces the risk
      for it. A higher neonatal mortality and morbidity, including neurological and
      neuromotoric dysfunctions is expected in this clinical entity.

PMID- 16815470
TI  - Sonographic prediction of significant intertwin birth weight discordance.
AB  - OBJECT: To evaluate the usefulness of sonographic prediction of significant birth
      weight discordance in twin pregnancies. STUDY DESIGN: Included in the study were
      live twin pairs with a gestational age of 24 weeks at birth who had received a
      sonographic examination within 28 days of delivery. Correlation tests and ROC
      curves were used to evaluate the predictability of significant intertwin growth
      discordance. RESULTS: A total of 575 twin pregnancies were included in the study.
      The estimated discordance by sonographic examination proved to be an effective
      predictor of discordant twin growth. The birth weight discordance estimated by
      sonography tended to underestimate the degree of discordant twins. CONCLUSION: If
      a sonographic examination is done within 28 days of delivery, it is a reliable
      predictor of twin birth weight discordance at the following levels: 15%, 20%, 25%
      or 30%. In order to obtain a higher sensitivity, the cut-off value of estimated
      birth weight discordance needs to be decreased by 5%.

PMID- 16815471
TI  - Phosphodiesterase-5 inhibitors and omental and placental small artery function in
      normal pregnancy and pre-eclampsia.
AB  - OBJECTIVES: In pre-eclampsia (PE), endothelium-dependent function of myometrial
      small arteries is markedly attenuated. The residual PE response is wholly NO
      mediated. We have previously demonstrated that PDE5 inhibition can improve
      endothelial function in myometrial small arteries from women with PE. We aimed to
      assess whether the effect of PDE5 inhibition in PE was myometrial artery
      specific. STUDY DESIGN: Small arteries were dissected from omental biopsies
      obtained at Caesarean section from normal pregnant women (NP, N = 20) and women
      with PE (N = 11). Chorionic plate small arteries were dissected from NP (N = 13)
      and PE (N = 11) placentae. Vasoconstriction (arginine vasopressin or thromboxane
      mimetic U46619) and endothelial-dependent relaxation were assessed by wire and
      pressure myography. Constriction/relaxation curves were repeated post 1h
      incubation with PDE5 inhibitors UK-343664 or sildenafil citrate (0, 10 or 100
      nM). RESULTS: Omental artery constriction was increased in PE. Omental vessel
      constriction was unaffected by PDE5 inhibition. Sildenafil citrate improved
      bradykinin-induced but not acetylcholine-induced relaxation of omental small
      arteries from NP women. PDE5 inhibition did not alter relaxation of omental
      arteries from women with PE. Placental small arteries were unaffected by PDE5
      inhibition. CONCLUSION: Use of PDE5 inhibitors does not significantly alter
      endothelial-dependent relaxation in omental or placental small arteries from PE
      women.

PMID- 16815472
TI  - The effect of adenosine 5'-triphosphate on calcium mobilization and cell
      proliferation in cervical cancer cells.
AB  - OBJECTIVE: To know the effect of adenosine 5'-triphosphate (ATP) on intracellular
      calcium level and cell proliferation in cervical cancer cells. STUDY DESIGN: Four
      different human cervical cancer cell lines (Caski, C33A, HeLaS3 and SiHa) were
      used in this study. The change of intracellular calcium level, cell proliferation
      and the activity of proliferation- and calcium-related transcription factors by
      extracellular ATP were examined in these cell lines. RESULTS: Extracellular ATP
      induced calcium mobilization, cell proliferation and the activation of NF-kappaB
      in all cell lines used. CONCLUSION: These results suggest that calcium
      mobilization and NF-kappaB dependent signaling pathway play an important role in
      the cell proliferation by ATP in cervical cancer.

PMID- 16815473
TI  - Long-term efficacy of transcervical endometrial resection with no preoperative
      hormonal preparation.
AB  - OBJECTIVE: To assess the level of patient satisfaction after transcervical
      endometrial resection (TCRE) with no preoperative hormonal preparation. STUDY
      DESIGN: A retrospective audit of a continuous case series was accomplished on 131
      consecutive patients who underwent TCRE for dysfunctional uterine bleeding. Data
      of postal questionnaires were analysed and subjected to survival analysis.
      RESULTS: Thirty-three cases were lost to follow-up; thus, the data on 98 of the
      131 (74.8%) patients were analysed. The average follow-up period was 94.8 months
      (60-132). Twenty (20.4%) women required D&C and 15 (15.3%) had hysterectomy. In
      eight of the 15 cases, the indication for hysterectomy was not related with the
      primary operation. The chance of avoiding hysterectomy reached a plateau after 72
      months, at 78.3% (SE: 5.05%). The chance of avoiding D&C at up to 36 months was
      98.6% (SE: 1.4%), and reached a plateau after 107 months at 67.11% (SE: 6.1%);
      55.8% of the patients became amenorrhoeic, the remaining cases reporting good
      improvements in the amount and duration of bleeding, and dysmenorrhoea. Eighty
      six of the 98 patients (88%) were satisfied or very satisfied with the result.
      CONCLUSIONS: TCRE affords reasonable long-term effectiveness in the treatment of
      dysfunctional uterine bleeding, even without any preoperative hormonal
      endometrial preparation.

PMID- 16815474
TI  - Antioxidative enzyme and glutathione S-transferase activities in diabetic rats
      exposed to long-term ASA treatment.
AB  - Low-dose acetylsalicylic acid (ASA) treatment is a standard therapeutic approach
      in diabetes mellitus for prevention of long-term vascular complications. The aim
      of the present work was to investigate the effect of long-term ASA administration
      in experimental diabetes on activities of some liver enzymes: glutathione
      peroxidase (GSHPx), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and
      glutathione S-transferase (GST). Blood glucose, glycated hemoglobin, as well as
      plasma ALT and AST activities increased in rats with streptozotocin-induced
      experimental diabetes. The long-term hyperglycemia resulted in decreased
      activities of GSHPx (by 26%), catalase (by 34%), GST (by 38%) and G6PDH (by 27%)
      in diabetic animals. We did not observe increased accumulation of membrane lipid
      peroxidation products or altered levels of reduced glutathione in livers. The
      linear correlation between blood glucose and glycated hemoglobin in diabetic
      animals was distorted upon ASA treatment, which was likely due to a chemical
      competition between nonenzymatic protein glycosylation and protein acetylation.
      The long-term ASA administration partially reversed the decrease in GSHPx
      activity, but did not influence the activities of catalase and GST in diabetic
      rats. Otherwise, some decrease in these parameters was noted in ASA-treated
      nondiabetic animals. Increased ASA-induced G6PDH activity was recorded in both
      diabetic and nondiabetic rats. While both glycation due to diabetic hyperglycemia
      and ASA-mediated acetylation had very similar effects on the activities of all
      studied enzymes but G6PDH, we conclude that non-enzymatic modification by either
      glucose or ASA may be a common mechanism of the observed convergence.

PMID- 16815475
TI  - Diazoxide-induced cardioprotection via DeltaPsim loss depending on timing of
      application.
AB  - Although the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in
      cardioprotection is widely accepted, it remains unclear when their opening is
      critical for protection. We tested the hypothesis that the mitoKATP channel acts
      as a trigger or mediator of protection against apoptosis through loss of
      mitochondrial inner membrane potential (DeltaPsim). Exposure of neonatal rat
      cardiomyocytes to H2O2 (0.5 mmol/L) resulted in apoptosis associated with severe
      DeltaPsim loss. Pretreatment with diazoxide (20 to 100 micromol/L) prevented H2O2
      induced apoptosis and DeltaPsim loss at 2 but not 18 h after exposure, while the
      latter was prevented by cotreatment with diazoxide. Lack of protection by
      pretreatment with diazoxide was observed in cardiomyocytes cultured in a medium
      containing H2O2 for 2 h and then not containing for 16 h. The slopes of the
      regression lines of the relationship between the proportion of apoptotic cells
      and DeltaPsim loss (y = -0.89 vs. -0.42) and the proportion of cells with high
      side scatter signal differed between cardiomyocytes exposed H2O2 for 2 and 18 h.
      Diazoxide per se caused a transient DeltaPsim loss (within 30 min) with a
      recovery followed by persistent DeltaPsim loss (after 6 h). Inhibition of the
      former by 5-hydroxydecanoate (5-HD, 0.5 mmol/L) abolished protection of
      pretreatment with diazoxide (trigger phase), while that of the latter prevented
      the protection of cotreatment with diazoxide (mediator phase). Our results
      suggest that mitoKATP channels act as a trigger and mediator of cardioprotection
      through a transient or persistent DeltaPsim loss depending on phenotypic
      consequence in response to oxidants.

PMID- 16815476
TI  - Lysophosphatidic receptor, LPA3, is positively and negatively regulated by
      progesterone and estrogen in the mouse uterus.
AB  - Reciprocal interactions between blastocysts and receptive uteri are essential for
      successful implantation. This process is regulated by the timely interplay of two
      ovarian hormones, progesterone and estrogen. However, the molecular targets of
      these hormones are largely unknown. We showed recently that a small bioactive
      lysophospholipid, lysophosphatidic acid, plays a pivotal role in the
      establishment of implantation via its cellular receptor, LPA(3). Here we
      demonstrate that LPA(3) expression is positively and negatively regulated by
      steroid hormones in mouse uteri. The LPA(3) mRNA level in the uteri increased
      during early pseudopregnancy, peaking around 3.5 days post coitus (3.5 d.p.c.),
      then, decreased to the basal level on 4.5 d.p.c. LPA(3) expression remained at a
      low level in ovariectomized mice, and administration of progesterone to
      ovariectomized mice up-regulated LPA(3) mRNA expression. In addition,
      simultaneous administration of estrogen counteracted the effect of progesterone.
      These results show that progesterone and estrogen cooperatively regulate LPA(3)
      expression, thereby contributing to the receptivity of uteri during early
      pregnancy.

PMID- 16815477
TI  - Therapeutic potential of RNA interference for neurological disorders.
AB  - During the past decade, numerous molecular mediators of neurodegenerative
      diseases and neurological disorders have been identified and validated, yet few
      novel therapies have emerged and the unmet medical needs remain high. These
      molecular mediators belong to target classes such as ion channels,
      neurotransmitters and neurotransmitter receptors, cytokines, growth factors,
      enzymes and other proteins. In some cases, substantial pre-clinical validation
      exists, but the molecular target has not been readily druggable with small
      molecules, proteins or antibodies. RNA interference represents a therapeutic
      approach applicable to such non-druggable targets. Both non-viral and viral
      delivery strategies are being undertaken for in vivo silencing of molecular
      targets by RNA interference, which has resulted in robust efficacy in animal
      models of Alzheimer's disease, ALS, Huntington's disease, spinocerebellar ataxia,
      anxiety, depression, neuropathic pain, encephalitis and glioblastoma. These proof
      of-concept data in animal models, together with the commencement of clinical
      trials using RNA interference for macular degeneration and respiratory syncytial
      virus infection, point to the potential of direct RNA interference for
      neurological disorders and neurodegenerative diseases.

PMID- 16815478
TI  - Evidence for an age-related attenuation of cerebral microvascular antioxidant
      response to oxidative stress.
AB  - Effects of aging and oxidative stress were studied in cerebral microvessels and
      microvessel-depleted brain from 6-, 18-, and 24-month-old C57Bl/6J mice exposed
      to normoxia, 24 or 48 h hyperoxia, or 24 h hyperoxia followed by 24 h normoxia.
      Microvessels lacked smooth muscle and consisted predominantly of endothelium.
      Following exposure and isolation of microvessel and parenchymal proteins, Western
      blot analysis was performed for detection of cytosolic thioredoxin 1 (TRx 1) and
      mitochondrial thioredoxin 2 (TRx 2), protein carbonyl, and mitochondrial
      superoxide dismutase (MnSOD). Both microvessel and parenchymal TRx 1 levels were
      increased by hyperoxia; however, the microvascular response was limited and
      delayed in comparison to that of the parenchymal fraction. Whereas TRx 2 levels
      in microvessels were increased in older mice, irrespective of exposure condition,
      hyperoxia per se had little or no apparent effect. Parenchymal cells showed no
      age-related increase in TRx 2 level under normoxic conditions, but showed
      increased levels following hyperoxia. Microvessel MnSOD was lower than that in
      parenchymal cells, but increased with age under normoxia, and also was correlated
      with the duration of hyperoxia. Although hyperoxia augmented MnSOD levels in
      young (6 months) and middle-aged (18 months) animals, the response was less
      pronounced in microvessels from senescent, 24-month-old mice. Unlike
      microvessels, which showed a sustained age-related increase in MnSOD level under
      each exposure condition, parenchymal cells from normoxic mice showed no increase,
      and hyperoxia-induced elevations declined with prolonged 48 h exposure. These
      results indicate that the microvessel endothelium is (1) subjected to a more
      intense oxidative environment than neurons and glia and (2) is limited by aging
      in its ability to respond to oxidative insult.

PMID- 16815479
TI  - Stereological estimation of Purkinje neuron number in C57BL/6 mice and its
      relation to associative learning.
AB  - Cerebellar Purkinje neurons are among the most vulnerable neurons in the CNS.
      Impairment in Purkinje neurons has consequences for cerebellar cortical-dependent
      forms of behavior. The primary aim of this study was to evaluate Purkinje neuron
      number over the lifespan of C57BL/6 mice. Stereological estimates of the total
      number of Purkinje neurons in cerebellar cortex were made in 25 C57BL/6 mice aged
      4, 8, 12, 18, and 24 months. Delay eyeblink classical conditioning to a white
      noise conditioned stimulus was also assessed for 10 daily sessions. Statistically
      significant age differences in Purkinje neuron number were observed beginning at
      18 months. Delay eyeblink conditioning also showed significant age-related
      impairment, at least some of which resulted from age-related deficits in hearing.
      Eliminating the hearing-impaired 18- and 24-month-old mice from the analysis, the
      correlation between Purkinje neuron number and rate of conditioning was -0.435
      (P=0.053) in 15 younger mice aged 4-12 months. Purkinje neurons are one of the
      few types of neurons showing significant age-associated loss. Results indicate
      that individual variation in Purkinje neuron number is related to eyeblink
      conditioning in young organisms suggesting that reserves of neuron numbers
      against which individuals draw are defined early in life.

PMID- 16815480
TI  - Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal
      slices.
AB  - This work reports the effect of chemokine fractalkine/CX3CL1, an endogenous small
      peptide highly expressed in the central nervous system, on evoked synaptic
      responses investigated in mouse CA1 stratum radiatum using an
      electrophysiological approach. We report that in acute mouse hippocampal slices,
      superfusion of CX3CL1 resulted in a reversible depression of the field excitatory
      postsynaptic potential (fEPSP) which developed within few seconds, increased for
      up to 10 min of application and disappeared within 30 min after the end of CX3CL1
      treatment. We also show that CX3CL1-induced synaptic depression is (i) dose
      dependent with IC50 and nH values of 0.7 nM and 1, respectively, (ii) not
      associated with a change in paired-pulse facilitation, (iii) mediated through
      CX3CL1 receptor (CX3CR1), being absent in CX3CR1-/- mice and inhibited in wild
      type mice by a specific blocking antibody, and (iv) occluded by the induction of
      homosynaptic long-term depression (LTD). We conclude that CX3CL1 is a potent
      neuromodulator of the evoked excitatory synaptic transmission, sharing common
      mechanisms with LTD.

PMID- 16815481
TI  - Differential redistribution of native AMPA receptor complexes following LTD
      induction in acute hippocampal slices.
AB  - AMPAR trafficking is crucial for the expression of certain forms of synaptic
      plasticity. Here, using surface biotinylation of hippocampal slices and
      subsequent synaptosome isolation we assessed AMPAR surface expression in
      synaptosomes following NMDA-evoked long-term depression (NMDA-LTD). Surface
      levels of GluR1, GluR2 and GluR3 in synaptosomes were markedly reduced 90 min
      after NMDA-LTD induction. Consistent with endocytosis and degradation, whole-cell
      surface and total expression levels of GluR2 and GluR3 were also reduced. In
      contrast, whole-cell surface levels of GluR1 were unaltered at 90 min suggesting
      that AMPARs with different subunit composition are redistributed to different non
      synaptic compartments following LTD induction in acute hippocampal slices.

PMID- 16815482
TI  - Inhibition of tetanically sciatic stimulation-induced LTP of spinal neurons and
      Fos expression by disrupting glutamate transporter GLT-1.
AB  - Tetanic stimulation of the sciatic nerve produces spinal long-term potentiation
      (LTP) of C-fiber evoked field potentials, which is NMDA dependent and may be the
      substrate of inflammation- or nerve injury-produced central sensitization. Glial
      glutamate transporter GLT-1 has been considered as an important regulator of
      excitatory synaptic transmission and nociception. In the present study, we
      investigated the effects of GLT-1 on the spinal LTP and Fos expression induced by
      tetanically sciatic stimulation. Intrathecal administration of dihydrokainate
      (DHK), a GLT-1 selective inhibitor, partially inhibited (0.1 mM) or completely
      blocked (3.0 mM) the spinal LTP, which may be related to an accumulation of
      extracellular glutamate. Intrathecal DHK (3.0 mM) also suppressed tetanic
      stimulation-induced spinal Fos expression. Double immunofluorescence showed no
      Fos expression in glial fibrillary acidic protein (GFAP)-positive cells, and the
      cell DNA fragment study failed to detect a significant apoptosis of spinal
      neurons. These results suggest that disruption of GLT-1 may be associated with
      the inhibition of functional activation of spinal neurons expressing Fos, but not
      with glutamate excitotoxicity. In conclusion, glial GLT-1 may play an important
      role in tetanically sciatic stimulation-induced LTP of spinal nociceptive neurons
      via the regulation of extracellular levels of glutamate to an appropriate
      concentration.

PMID- 16815483
TI  - Cyclosporin A inhibits apolipoprotein A-I-induced early events in cellular
      cholesterol homeostasis in rat astrocytes.
AB  - In the biogenesis of HDL by exogenous apolipoprotein (apo) A-I in rat astrocytes,
      apoA-I induced translocation of phospholipase Cgamma (PLCgamma) and PKCalpha to
      cytosolic lipid protein particle (CLPP) [Ito et al., 2004. J. Lipid Res. 45,
      2269] and caused tyrosine-phosphorylation of PLCgamma in CLPP in the initial 5
      min. It also induced translocation of caveolin-1 and newly synthesized
      cholesterol and phospholipid to CLPP, and increased cholesterol biosynthesis
      prior to the HDL biogenesis [Ito et al., 2002a. J. Biol. Chem. 277, 7929].
      Cyclosporin A (CsA), an indirect inhibitor of protein phosphatase 2B (PP2B) and a
      potential inhibitor of ABC transporter A1 (ABCA1), suppressed all of these apoA-I
      induced cellular events. CsA, however, did not affect the basal lipid release by
      the production of HDL with endogenous apoE, except for moderate decrease of its
      cholesterol content. Direct inhibitors of PP2B, inhibited only the release of
      lipids by apoA-I and had no effect on other apoA-I-induced events. CsA thus
      interferes with cellular cholesterol homeostasis independently of PP2B
      inhibition, perhaps by direct inhibition of ABCA1 reactivity to exogenous apoA-I,
      although PP2B may be involved in the lipid release step. CsA could therefore
      cause some neurological side effects by interfering with cellular cholesterol
      homeostasis in the brain.

PMID- 16815484
TI  - Energy metabolism in infants with congenital heart disease.
AB  - Failure to thrive is common in children with congenital heart disease and
      influences the metabolic response to injury and outcome after corrective cardiac
      surgery. Energy imbalance is a major contributing factor. However, the published
      literature is difficult to interpret as studies generally involve small patient
      numbers with a diverse range of types and severity of cardiac lesions and genetic
      and/or prenatal factors. The age and time of corrective surgery affects the
      potential for nutritional recovery. Although the immediate postoperative period
      is characterized by a hypermetabolic state, low total and resting energy
      expenditure are reported within 24 h of surgery. After 5 d, resting energy
      expenditure returns to preoperative levels. Significant improvements in weight
      and growth occur within months after corrective surgery. However, limited
      postoperative recovery in nutritional status and growth occurs in infants with a
      low birth weight, intellectual deficit, or residual malformation. Further studies
      are needed to inform the timing of corrective cardiac surgery to maximize
      nutritional outcomes and to identify those infants who may benefit from
      aggressive preoperative nutrition support.

PMID- 16815485
TI  - Controlled study of enteral arginine supplementation in burned children: impact
      on immunologic and metabolic status.
AB  - OBJECTIVE: We compared the effects of an arginine-supplemented diet with those of
      an isocaloric isonitrogenous diet on immune and metabolic response of children
      with burns. METHODS: This was a double-blind, randomized, placebo-controlled
      trial in a burn treatment center of a pediatric hospital in Santiago, Chile. All
      children (1-5 y of age) admitted within 48 h of a moderate to deep burn injury
      covering 10% to 40% of total body surface area were evaluated. Twenty-eight
      children met the criteria and were randomly assigned to receive an arginine
      supplemented diet (AG; n = 14) or an isocaloric isonitrogenous diet (CG; control,
      n = 14) for 14 d. Samples were collected at admission (baseline) and on days 7
      and 14 for lymphoproliferative response to mitogens, plasma interleukins
      (interleukin-1, interleukin-6, tumor necrosis factor-alpha), plasma arginine and
      ornithine levels, serum C-reactive protein, prealbumin, albumin, glucose, and
      total urinary nitrogen. RESULTS: The AG enhanced lymphoproliferative responses
      (analysis of variance, P < 0.05), which were 72% of normal at baseline in both
      groups; by day 7 responses increased to 144% in the AG group and decreased to 56%
      in the CG group; both groups returned to normal by day 14. Baseline interleukin-6
      was significantly increased in all children. There were no differences in plasma
      concentrations of interleukin-1, interleukin-6, tumor necrosis factor-alpha, C
      reactive protein, prealbumin, albumin, or glucose between the AG and CG groups.
      On day 7 plasma ornithine levels increased significantly in the AG versus CG
      group (P < 0.05); arginine levels showed no change. CONCLUSIONS: An exclusively
      AG improves mitogen-stimulated lymphocyte proliferation in burned children. The
      benefits of arginine for the immune system do not appear to be related to a
      metabolic response. The biological significance of this finding remains to be
      determined.

PMID- 16815486
TI  - Effects of long-term continuous use of immune-enhancing enteral formula on
      nutritional and immunologic status in non-surgical patients.
AB  - OBJECTIVE: Although the perioperative use of immune-enhancing enteral formula
      (IEEF) effectively reduces the rate of infectious complications, whether chronic
      use of IEEF is beneficial is unknown. A prospective randomized clinical trial was
      performed to examine the safety and effectiveness of long-term IEEF on
      nutritional and immunologic status in non-surgical patients receiving total
      enteral nutrition through the gastrostomy access route. METHODS: A total of 30
      patients were randomly assigned to two groups in which they received total
      enteral nutrition, an IEEF (n = 15) or a regular polymeric enteral formula
      (control group; n = 15) for 12 wk. Nutritional and immunologic variables were
      periodically examined. RESULTS: Serum concentrations of insulin-like growth
      factor-I increased significantly for the IEEF group throughout the study.
      Although serum concentrations of dihomo-gamma-linoleic acid decreased
      significantly in the IEEF group, serum concentrations of eicosapentaenoic acid
      and docosahexaenoic acid increased significantly, as did concentrations of serum
      arginine and ornithine. The CD4/CD8 ratio and natural killer cell activity also
      increased for the IEEF group, but the differences were not significant. The B
      cell fraction increased and the T-cell fraction of peripheral lymphocytes
      decreased for the IEEF group. Neither infectious nor non-infectious complications
      occurred during the study period in either group, except for a significant
      increase in serum urea nitrogen and uric acid concentrations for the IEEF group.
      CONCLUSION: Long-term use of IEEF is safe in non-surgical patients and results in
      a significant increase in serum insulin-like growth factor-I concentrations in
      association with increased humoral immunity.

PMID- 16815487
TI  - Fat oxidation and plasma removal capacity of an intravenous fat emulsion in
      elderly and young men.
AB  - OBJECTIVE: We explored metabolic and thermogenic responses to exogenous fat in
      relation to age as a basis for a rational design of parenteral nutrition in
      elderly patients. METHODS: Ten healthy elderly men (70-78 y of age, body mass
      index 21-27 kg/m(2)) and 10 healthy young men (19-45 y of age, body mass index 19
      26 kg/m(2)) were studied with a hypertriglyceridemic clamp (primed infusion of a
      long-chain triacylglycerol emulsion to reach and stabilize at a triacylglycerol
      concentration of 4 mmol/L for 180 min). Continuous indirect calorimetry was
      carried out in the basal state and throughout the study period. RESULTS: The
      infusion rates required to maintain plasma triacylglycerol levels at 4 mmol/L
      were similar in elderly and young individuals (mean +/- SEM 0.201 +/- 0.027
      versus 0.203 +/- 0.014 mmol/min, not significant). Plasma concentrations of free
      fatty acids and beta-OH-butyrate were higher in the elderly before the infusion
      and increased in a similar manner in both groups during infusion. Energy
      expenditure at baseline was higher in the young than in the elderly (79 +/- 2
      versus 64 +/- 3 kcal/h; P < 0.001), although the respiratory quotient was similar
      in the two groups (0.80 +/- 0.01 versus 0.78 +/- 0.01, not significant). During
      lipid administration there was a similar increase in energy expenditure in the
      old and young individuals (+9.0 +/- 1.3% versus +6.0 +/- 1.8%, not significant).
      Lipid infusion resulted in similar increments in fat oxidation in the young and
      elderly (23.9 +/- 7.0% versus 15.1 +/- 4.9%, respectively, not significant).
      Plasma lipoprotein lipase activity was almost three times higher in the young
      than in the elderly subjects (0.23 +/- 0.02 versus 0.65 +/- 0.09 mU/mL,
      respectively, P < 0.001). During lipid infusion, a similar increment (four- to
      five-fold) in plasma lipoprotein lipase activity was noted in the two groups.
      CONCLUSIONS: Elderly healthy men have a similar capacity as young healthy men to
      clear and oxidize a high triacylglycerol load administered as a
      hypertriglyceridemic clamp.

PMID- 16815488
TI  - Fiber intake, constipation, and overweight among adolescents living in Sao Paulo
      City.
AB  - OBJECTIVE: This study evaluated the dietary fiber intake of adolescents in the
      metropolitan area of Sao Paulo city and any association between low dietary fiber
      intake with constipation and overweight. METHODS: In total, 716 adolescents were
      included within the study, of whom 314 attended private school and 402 attended
      public school. Evaluation of fiber intake was based on a 24-h daily intake record
      and a frequency questionnaire. Data concerning bowel movements and height and
      weight measurements were also taken. RESULTS: Fiber consumption, below that
      recommended ("age + 5"), was found in 61.8% and 41.4% (P = 0.000) of girls
      attending private and public schools, respectively, and in 44.1% and 25.6% of
      boys (P = 0.001). Adolescents who did not eat beans on more than 4 d/wk presented
      a higher risk of fiber intake below that recommended (age + 5; P < 0.05), with
      odds ratios ranging from 10.4 to 14.2 according gender and private or public
      schooling. Dietary fiber intake below that recommended was associated with a
      greater risk (P < 0.05) toward overweight in students attending public schooling
      (odds ratios 2.84 and 2.95 for males and females, respectively). Low dietary
      fiber intake was not associated with constipation. CONCLUSION: Intake of beans
      more than four times per week is associated with the appropriate level of fiber
      intake. Dietary fiber intake below the recommendation was not associated with
      constipation but was associated with being overweight among those students
      attending public schooling.

PMID- 16815489
TI  - Effects of acute-phase response on nutritional status and clinical outcome of
      hospitalized patients.
AB  - OBJECTIVE: We measured the effects of acute-phase response on nutritional status
      and clinical outcome in hospitalized older patients. METHODS: Four hundred forty
      five patients who took part in a randomized, double-blind, placebo-controlled
      trial of nutritional supplementation had their nutritional status assessed from
      anthropometric, hematologic, and biochemical data at baseline, 6 wk, and 6 mo.
      Outcome measures including disability, length of stay, and 1-y mortality were
      recorded. C-reactive protein (CRP) concentration, a marker of acute-phase
      response, was also measured. Multivariate analysis was used to measure the
      association between acute-phase response and nutritional assessment variables
      after adjusting for age, disability, chronic illness, medications, and smoking.
      RESULTS: Energy intake in the hospital was significantly lower among patients
      with higher CRP concentrations. Serum albumin, transferrin, plasma ascorbic acid,
      and hemoglobin concentrations were significantly lower and serum ferritin higher
      in patients with acute-phase response (CRP > 10 mg/L) than in patients without
      acute-phase response (CRP < or = 10 mg/L; P < 0.001). Nutritional status
      deteriorated among patients with acute-phase response in contrast to the
      improvement seen in patients without acute-phase response. After adjusting for
      age, disability, and comorbidity in a multivariate analysis, acute-phase response
      had a significant and independent effect on nutritional status and clinical
      outcome. The benefit of nutritional support was mainly confined to patients with
      acute-phase response. CONCLUSION: Acute-phase response is associated with poor
      nutritional status and poor clinical outcome in older patients. Whether
      nutritional support removes or mitigates the hazard of poor outcome associated
      with acute-phase response needs to be determined.

PMID- 16815490
TI  - Fructose-enriched diet modifies antioxidant status and lipid metabolism in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: High-fructose consumption in industrial countries has been shown to
      induce metabolic abnormalities or syndrome X. Changes in antioxidant defense are
      unknown in hypertension associated with metabolic disorders induced by high
      fructose feeding. METHODS: Twenty spontaneously hypertensive rats were assigned
      to one of two groups; one received a fructose-enriched diet (60% fructose) and
      the other a starch diet. After a 13-wk diet period, total antioxidant status was
      assessed in the blood and liver by monitoring the rate of free radical-induced
      red blood cell hemolysis. Antioxidants (enzymes and vitamins) were determined in
      blood and liver. Gene expression of antioxidant enzymes (copper/zinc superoxide
      dismutase and glutathione peroxidase) were also investigated in hepatic tissue.
      RESULTS: Fructose-fed rats showed blood pressure values similar to that of
      control rats but had increased glycemia and insulinemia. The antioxidant capacity
      in the blood of the fructose-fed group represented by copper/zinc superoxide
      dismutase and glutathione peroxidase activities and ascorbic acid was lower.
      However, the fructose diet enhanced the total antioxidant capacity of liver
      correlated with increased antioxidant enzyme activities and retinol
      concentrations. Gutathione peroxidase mRNA expression was decreased in livers of
      spontaneously hypertensive rats fed the fructose diet. CONCLUSION: Fructose
      feeding negatively affects antioxidant capacity in the blood of hypertensive rats
      but improves this capacity in the liver.

PMID- 16815491
TI  - Dietary supplementation with antioxidants improves functions and decreases
      oxidative stress of leukocytes from prematurely aging mice.
AB  - OBJECTIVES: Aging is accompanied by chronic inflammation and oxidative stress,
      which lead to a marked impairment of immune function and therefore increased
      mortality. This study assessed the effect of dietary supplementation, for 15 wk,
      with 5% and 20% (w/w) of biscuits enriched with nutritional doses of vitamins C
      and E, zinc, selenium, and beta-carotenes on function and oxidative stress
      parameters of peritoneal leukocytes from middle-aged, prematurely aging mice
      (PAM) and non-prematurely aging mice (NPAM). METHODS: After supplementation we
      measured leukocyte functions (adherence, chemotaxis, phagocytosis, intracellular
      reactive oxygen species levels, lymphoproliferation, natural killer activity, and
      interleukin-2 release), antioxidant defenses (superoxide dismutase, glutathione
      peroxidase, and reduced glutathione), oxidant compounds (extracellular O(2)(-),
      glutathione disulfide, glutathione disulfide/reduced glutathione ratio, tumor
      necrosis factor-alpha, nitric oxide, and prostaglandin E(2)), and lipid and DNA
      oxidative damage, measured by malondialdehyde and 8-oxo,7,8-dihydro-2'
      deoxyguanosine levels, respectively. RESULTS: In general, leukocyte functions
      were improved and redox homeostasis was restored after intake of antioxidants. In
      consequence, malondialdehyde and 8-oxo,7,8-dihydro-2'-deoxyguanosine in PAM and
      NPAM were strikingly decreased after 5% and 20% supplementation (malondialdehyde,
      P < 0.001 in PAM; P < 0.01 in NPAM after both treatments; 8-oxo,7,8-dihydro-2'
      deoxyguanosine, P < 0.01 after 5% supplementation and P < 0.001 after 20%
      supplementation in PAM and NPAM). Moreover, the effect of the antioxidants was
      stronger in PAM than in NPAM, and 20% supplementation was more effective than 5%.
      CONCLUSION: Our data suggest that improvement of leukocyte function and
      restoration of redox balance after consumption of adequate levels of antioxidants
      from adulthood may be useful to attain healthy aging, especially in animals with
      premature aging.

PMID- 16815492
TI  - Alterations in glutamine synthetase activity in rat skeletal muscle are
      associated with advanced age.
AB  - OBJECTIVE: Glutamine synthetase (GS), a key enzyme in the production of
      glutamine, is preserved in skeletal muscle during early aging (<24 mo). Because
      the effects of advanced age on GS are unknown, we investigated the effect of
      advanced age (>24 mo) on GS activity in skeletal muscle. We hypothesized that
      advanced age would enhance muscle GS activity. METHODS: Muscle GS activities were
      assessed in adult (8 mo), mature adult (15 mo), aged (20-22 mo), advanced age (25
      27 mo), or very advanced age (29-32 mo) female Wistar rats. Male Wistar (6-27 mo)
      were used to investigate the effect of gender on this activity. RESULTS:
      Glutamine synthetase activity remained low and unaltered in rats from 8 to 22 mo
      of age, as previously demonstrated. In contrast, GS activity was high (
      approximately 75% of individual values were higher than the low value mean) in 25
      mo to 27-mo-old rats. In very-old-aged rats (29-32 mo), approximately 55% of GS
      activity data points exhibited low values. Changes in GS protein content
      paralleled those in GS activities. In male rats, GS activity was also high (
      approximately 80% of individual values were higher than the mean value of 6-mo to
      19-mo-old rats) at the upper limit of life expectancy (27 mo). CONCLUSION: There
      is enhanced GS activity in old female and male rats suggesting a greater need for
      glutamine. In some very old rats, low GS activity may be associated with
      longevity or reflect a limitation in glutamine production due to extremely
      advanced age per se.

PMID- 16815493
TI  - Ingestion of difructose anhydride III, a non-digestible disaccharide, prevents
      gastrectomy-induced iron malabsorption and anemia in rats.
AB  - OBJECTIVE: Total gastrectomy produces iron malabsorption and anemia, and several
      non-digestible carbohydrates promote mineral absorption. In this study, we
      examined the effects of feeding difructose anhydride III (DFAIII), a non
      digestible disaccharide, on gastrectomy-induced iron malabsorption and anemia in
      rats in comparison with those of feeding fructo-oligosaccharides (FOS). METHODS:
      Sham-operated and totally gastrectomized male Sprague-Dawley rats were fed the
      control, DFAIII (30 g/kg), or FOS (30 g/kg) diet for 4 wk. Feces and tail blood
      were collected at 2 and 4 wk to evaluate body iron status and iron absorption.
      RESULTS: Gastrectomy severely decreased net iron absorption, hemoglobin
      concentration, and hematocrit in the control dietary group. The decreased
      absorption in gastrectomized rats was restored to the sham control level by
      feeding the DFAIII or FOS diet. Iron absorption in sham rats was higher in the
      FOS and DFAIII groups than in the control group. Hemoglobin concentration and
      hematocrit in gastrectomized rats fed the DFAIII diet, but not the FOS diet,
      returned to levels comparable to the effects in sham rats fed the control diet.
      Feeding DFAIII increased short-chain fatty acid pools and decreased pH of cecal
      contents. These parameters for cecal fermentation correlated with iron
      absorption. CONCLUSIONS: DFAIII feeding restores gastrectomy-induced iron
      malabsorption, resulting in complete prevention of iron-deficiency anemia in
      rats. Cecal fermentation of DFAIII may contribute to the improvement in these
      gastrectomy-induced defects. Feeding with low level of FOS did not fully improve
      postgastrectomy anemia.

PMID- 16815494
TI  - Genistein suppresses antigen-specific immune responses through competition with
      17beta-estradiol for estrogen receptors in ovalbumin-immunized BALB/c mice.
AB  - OBJECTIVE: The aim of this study was to determine the effects of phytoestrogen
      genistein on antigen (Ag)-specific immune responses and elucidate the mechanisms
      underlying those effects. METHODS: Ovalbumin (OVA)-immunized BALB/c mice were
      administered genistein for 35 d, and OVA-specific immune responses were examined
      by measuring OVA-specific proliferative responses, production of cytokines, and
      antibody responses. To assess the effect of genistein on antibody responses to
      thymus-independent Ag, mice were immunized with 2,4,6-trinitrophenyl (TNP)-Ficoll
      instead of OVA. Effect of genistein on the functions of CD11c(+) dendritic cells
      was also examined. Finally, to determine the contribution of estrogen receptor to
      genistein-mediated immune regulation, mice that had been administered genistein
      were treated with the estrogen receptor antagonist ICI 182,780 and OVA-specific
      proliferative responses were examined. RESULTS: OVA-specific proliferative
      responses and interferon-gamma production levels were decreased in mice
      administered 20 mg/kg genistein compared with those in control mice without
      reduction in responses to anti-CD3 monoclonal (m)antibody. The level of OVA
      specific immunoglobulin (Ig)G1 was also decreased in mice administered genistein.
      Levels of OVA-specific IgG2a and IgG2b production and interleukin-4 production in
      response to OVA were not significantly different but tended to decrease in
      genistein-treated mice. Genistein administration did not influence the TNP
      specific IgM and IgG levels. Furthermore, genistein did not affect the Ag
      presenting activity of CD11c(+) dendritic cells. Treatment with ICI 182,780
      decreased OVA-specific proliferative responses, but genistein did not suppress
      these responses synergistically in mice treated with ICI 182,780. CONCLUSIONS:
      The results of this study suggest that genistein suppresses Ag-specific immune
      responses. The mechanism underlying the suppression is responsible for the
      competition of genistein with endogenous 17beta-estradiol for estrogen receptors.

PMID- 16815495
TI  - Beneficial immunomodulatory activity of Lactobacillus casei in malnourished mice
      pneumonia: effect on inflammation and coagulation.
AB  - OBJECTIVE: The effect of Lactobacillus casei CRL 431 immunomodulatory activity on
      inflammation and coagulation during pneumococcal pneumonia was investigated in
      malnourished mice. METHODS: Weaned mice were malnourished after they consumed a
      protein-free diet for 21 d. Malnourished mice were treated for 7 d with a
      balanced conventional diet (BCD) with L. casei supplementation (BCD+Lc) or
      without it. The malnourished control group received only a protein-free diet
      whereas well-nourished control (WNC) mice consumed BCD ad libitum. Mice were
      challenged by the intranasal route with pneumococci at the end of each dietary
      treatment. Lung injury, leukocyte recruitment, cytokine production, coagulation
      tests, and fibrin(ogen) deposition in lungs were evaluated. RESULTS: Malnourished
      control mice showed impaired leukocyte recruitment and cytokine production, and
      more severe lung injuries when compared with WNC mice. Coagulation tests were
      significantly impaired in malnourished control group versus WNC group. Repletion
      with BCD or BCD+Lc improved these parameters, but only BCD+Lc mice achieved the
      values of WNC mice. In addition, the interleukin-10 level was higher in the
      BCD+Lc group than in the WNC group. CONCLUSION: Repletion with supplemental L.
      casei accelerated recovery of the defense mechanisms against pneumococci by
      inducing different cytokine profiles. These cytokines would be involved in the
      improvement of the immune response and in the induction of a more efficient
      regulation of the inflammatory process, limiting the injury caused by infection.

PMID- 16815496
TI  - Intake of trans fatty acid-rich hydrogenated fat during pregnancy and lactation
      inhibits the hypophagic effect of central insulin in the adult offspring.
AB  - OBJECTIVE: Using rats we examined whether maternal intake of hydrogenated fat
      rich in trans fatty acids affects brain fatty acid profile, hypothalamic content
      of insulin receptor and insulin receptor substrate-1 proteins, and the hypophagic
      effect of centrally administered insulin in 3-mo-old male progeny. METHODS:
      Throughout pregnancy and lactation, Wistar rats ate isocaloric/normolipidic diets
      with soybean oil (control) or soybean oil-derived hydrogenated fat (trans diet)
      as a fat source. Upon weaning, the trans offspring continued on the trans diet
      (trans group) or were switched to a control diet (trans-control group). RESULTS:
      Compared with control rats, trans rats had lower brain levels of eicosapentaenoic
      acid. Compared with trans rats, trans-control rats had increased levels of total
      polyunsaturated fatty acids and arachidonic acid and decreased levels of trans
      fatty acids, saturated fatty acids, and monounsaturated fatty acids. Insulin
      receptor and insulin receptor substrate-1 levels were significantly lower (44%
      and 38%, respectively) in trans than in control rats. In trans-control rats,
      insulin receptor was 26% lower (P < 0.05), whereas insulin receptor substrate-1
      was 50% lower, than in control rats. Insulin decreased 24-h feeding in control
      (27%) and trans (38%) rats but failed to do so in trans-control rats. The latter
      group had increased serum glucose levels. CONCLUSIONS: The data suggest that the
      early (intrauterine/perinatal) exposure to hydrogenated fat rich in trans fatty
      acids programmed the hypothalamic feeding control mechanisms. As young adults,
      only trans-control animals showed loss of insulin-induced hypophagia, indicating
      that the mismatch between early and later nutritional environments was relevant.
      However, the trans group also showed signs of altered appetite signaling
      mechanisms, suggesting that the early adaptations may have deleterious
      consequences later in life.

PMID- 16815497
TI  - Proteolytic and lipolytic responses to starvation.
AB  - Mammals survive starvation by activating proteolysis and lipolysis in many
      different tissues. These responses are triggered, at least in part, by changing
      hormonal and neural statuses during starvation. Pathways of proteolysis that are
      activated during starvation are surprisingly diverse, depending on tissue type
      and duration of starvation. The ubiquitin-proteasome system is primarily
      responsible for increased skeletal muscle protein breakdown during starvation.
      However, in most other tissues, lysosomal pathways of proteolysis are stimulated
      during fasting. Short-term starvation activates macroautophagy, whereas long-term
      starvation activates chaperone-mediated autophagy. Lipolysis also increases in
      response to starvation, and the breakdown of triacylglycerols provides free fatty
      acids to be used as an energy source by skeletal muscle and other tissues. In
      addition, glycerol released from triacylglycerols can be converted to glucose by
      hepatic gluconeogenesis. During long-term starvation, oxidation of free fatty
      acids by the liver leads to the production of ketone bodies that can be used for
      energy by skeletal muscle and brain. Tissues that cannot use ketone bodies for
      energy respond to these small molecules by activating chaperone-mediated
      autophagy. This is one form of interaction between proteolytic and lipolytic
      responses to starvation.

PMID- 16815498
TI  - Pleiotropic actions of vitamin K: protector of bone health and beyond?
AB  - Vitamin K is a nutrient that was originally identified as an essential factor for
      blood coagulation. Recently, vitamin K has emerged as a potential protector
      against osteoporosis, atherosclerosis, and hepatocarcinoma. Accumulated evidence
      indicates that subclinical non-hemostatic vitamin K deficiency in extrahepatic
      tissues, particularly in bone and possibly in vasculature, exists widely in the
      otherwise healthy adult population. Vitamins K1 and K2 have been shown to exert
      protective effects against osteoporosis, although it is important that the
      beneficial effects will be further confirmed by large-scale, randomized, clinical
      trials. Increasing evidence implicates a role for vitamin K in calcification of
      arteries and atherogenesis. Moreover, the therapeutic potential of vitamin K2 as
      an antihepatoma drug has recently been highlighted. Most of the new biological
      functions of vitamin K in bone, vasculature, and hepatoma cells are considered
      attributable to promotion of gamma-carboxylation of glutamic acid residues in
      vitamin K-dependent proteins, which is shared by vitamins K1 and K2. In contrast,
      vitamin K2-specific, gamma-carboxylation-unrelated functions have also been
      demonstrated. Thus, biological differences between vitamins K1 and K2 and
      potential involvement of gamma-carboxylation-independent actions in the new roles
      of vitamin K remain open issues. Molecular bases of coagulation-unrelated
      pleiotropic actions of vitamin K and its implications in human health deserve
      further investigations.

PMID- 16815499
TI  - Drinking water as an iron carrier to control iron deficiency.

PMID- 16815500
TI  - Preface special issue 'Advances in Developmental Cognitive Neuroscience'.

PMID- 16815501
TI  - Co-administration of MK-801 and morphine attenuates neuropathic pain in rat.
AB  - Partial peripheral nerve injury often leads to chronic pain states, including
      allodynia and hyperalgesia. The purpose of this study was to investigate the
      involvement of the N-methyl-D-aspartate and opioid receptors in the behavioural
      responses following chronic constriction nerve injury (CCI). The animals were
      injected a combination of MK-801 (0.3 mg/kg, 20 min before, and 6 h after the
      operation) and morphine (8 mg/kg, 30 min prior to the operation) and were tested
      for allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after
      CCI. Compound action potentials were also recorded from the injured nerve 2 weeks
      post-operation to indicate nerve injury state electrophysiologically. Our results
      indicate that the CCI model importantly influences the behavioural responses to
      both the thermal and mechanical stimulations. Also, the pre-emptive co
      administration of MK-801 and morphine has suppressive effects on the cold
      allodynia but a slight alleviation on the mechano-allodynia and heat
      hyperalgesia.

PMID- 16815502
TI  - Tissue distribution and biosynthesis of 1,2-saturated pyrrolizidine alkaloids in
      Phalaenopsis hybrids (Orchidaceae).
AB  - Phalaenopsis hybrids contain two 1,2-saturated pyrrolizidine monoesters, T
      phalaenopsine (necine base trachelanthamidine) and its stereoisomer Is
      phalaenopsine (necine base isoretronecanol). T-Phalaenopsine is the major
      alkaloid accounting for more than 90% of total alkaloid. About equal amounts of
      alkaloid were genuinely present as free base and its N-oxide. The structures were
      confirmed by GC-MS. The quantitative distribution of phalaenopsine in various
      organs and tissues of vegetative rosette plants and flowering plants revealed
      alkaloid in all tissues. The highest concentrations were found in young and
      developing tissues (e.g., root tips and young leaves), peripheral tissues (e.g.,
      of flower stalks) and reproductive organs (flower buds and flowers). Within
      flowers, parts that usually attract insect visitors (e.g., labellum with colorful
      crests as well as column and pollinia) show the highest alkaloid levels. Tracer
      feeding experiments with (14)C-labeled putrecine revealed that in rosette plants
      the aerial roots were the sites of phalaenopsine biosynthesis. However active
      biosynthesis was only observed in roots still attached to the plant but not in
      excised roots. There is a slow but substantial translocation of newly synthesized
      alkaloid from the roots to other plant organs. A long-term tracer experiment
      revealed that phalaenopsine shows neither turnover nor degradation. The results
      are discussed in the context of a polyphyletic molecular origin of the
      biosynthetic pathways of pyrrolizidine alkaloids in various scattered angiosperm
      taxa. The ecological role of the so called non-toxic 1,2-saturated pyrrolizidine
      alkaloids is discussed in comparison to the pro-toxic 1,2-unsaturated
      pyrrolizidine alkaloids. Evidence from the plant-insect interphase is presented
      indicating a substantial role of the 1,2-saturated alkaloids in plant and insect
      defense.

PMID- 16815503
TI  - Robustness of central carbohydrate metabolism in developing maize kernels.
AB  - The central carbohydrate metabolism provides the precursors for the syntheses of
      various storage products in seeds. While the underlying biochemical map is well
      established, little is known about the organization and flexibility of
      carbohydrate metabolic fluxes in the face of changing biosynthetic demands or
      other perturbations. This question was addressed in developing kernels of maize
      (Zea mays L.), a model system for the study of starch and sugar metabolism. (13)C
      labeling experiments were carried out with inbred lines, heterotic hybrids, and
      starch-deficient mutants that were selected to cover a wide range of performances
      and kernel phenotypes. In total, 46 labeling experiments were carried out using
      either [U-(13)C(6)]glucose or [U-(13)C(12)]sucrose and up to three stages of
      kernel development. Carbohydrate flux distributions were estimated based on
      glucose isotopologue abundances, which were determined in hydrolysates of starch
      by using quantitative (13)C-NMR and GC-MS. Similar labeling patterns in all
      samples indicated robustness of carbohydrate fluxes in maize endosperm, and
      fluxes were rather stable in response to glucose or sucrose feeding and during
      development. A lack of ADP-glucose pyrophosphorylase in the bt2 and sh2 mutants
      triggered significantly increased hexose cycling. In contrast, other mutations
      with similar kernel phenotypes had no effect. Thus, the distribution of
      carbohydrate fluxes is stable and not determined by sink strength in maize
      kernels.

PMID- 16815504
TI  - Gender differences in adolescent injury characteristics: a population-based study
      of hospital A&E data.
AB  - OBJECTIVES: To investigate patterns of adolescent home/leisure injury serious
      enough to require hospital attendance. STUDY DESIGN: Population-based analysis of
      data collected by the Home and Leisure Accident Surveillance System (HASS/LASS).
      METHODS: Study subjects were 0-17 year old residents of Airdrie and Coatbridge,
      Lanarkshire, Scotland, who attended Monklands Hospital Accident and Emergency
      (A&E) Department with a home/leisure injury during calendar years 1996-1999. Male
      to female relative risk ratios (M:F RRRs) for A&E attendance, fracture and
      hospital admission, stratified into sports and non-sports injuries, were
      calculated. Sports injuries were further analysed by specific sports and by
      whether the sports activity was organized or informal. Data were analysed in age
      groups corresponding to children's stage of schooling. RESULTS: The M:F RRR for
      non-sports A&E attendances remained constant throughout childhood (1.35, 95% CI
      1.30-1.39 in 0-17 year olds), whilst that for sports attendances increased
      sharply with age (2.50, 95% CI 0.89-7.02 in 0-4 year olds, increasing to 8.11,
      95% CI 6.27-10.51 in 16-17 year olds). Of sports injury attendances, 50.3% were
      football-related. Football was overwhelmingly the main cause of boys' sports
      injury in both the organized and informal sports injury categories. When football
      injuries were excluded from the analysis, the widening teenage gender gap in
      injury risk disappeared. There was no significant gender difference in teenagers'
      rates of A&E attendance for injuries sustained during compulsory school physical
      education (PE), suggesting a dose-response relationship between sports
      participation and injury risk. CONCLUSIONS: This study found significant gender
      inequalities in adolescent injury risk, which were largely attributable to boys'
      football injuries. Focusing prevention efforts on making football safer would,
      then, be a sensible strategy for reducing the overall burden of adolescent injury
      and for reducing sex inequalities in injury risk; however further research is
      needed to understand how the risks differ between organized and informal
      football. These findings are also interesting because of what they suggest about
      teenage girls' lack of participation in sport and habitual physical activity.
      This is clearly of public health concern because of the links between physical
      inactivity and a range of health problems.

PMID- 16815505
TI  - A systematic review of measures of effectiveness in screening for oral cancer and
      precancer.
AB  - Nine databases were searched for studies reporting a range of measures on the
      effectiveness of screening for oral cancer and precancer in primary care. Of 1114
      papers generated in a search of nine databases, full texts of 90 were scrutinised
      by two reviewers to ensure that they were concerned with oral cancer/precancer,
      reported an oral cancer screening programme/exercise and included at least one
      effectiveness outcome. Criteria for considering studies for the review covered
      types of studies, participants, interventions and outcome measures. The latter
      included measures of both end point and interim outcome and also process. Of 90
      full text articles screened, examiners agreed on the inclusion of 28 (initial
      agreement -- kappa=0.60). The remaining 62 were excluded and the reasons
      recorded. The studies included showed substantial heterogeneity regarding
      objectives and study design, location and setting, numbers and characteristics of
      participants, screening personnel, methods of recruitment and types of data
      collected. Only one study, from the Indian sub-continent, reported a randomised
      controlled trial: interim results showed 14.9% of intervention subjects died
      after 3 years compared with 56.3% of non-intervention controls. The review
      overall produced no evidence in favour of or against the potential benefits
      associated with an oral cancer screening programme. It was concluded that there
      are insufficient available data to make an unequivocal determination as to the
      effectiveness of oral cancer screening programmes at the present time. However, a
      recent further report on the Indian study published after completion of the
      review, provides some evidence that screening for oral cancer may be effective,
      at least in developing countries with a high incidence of the disease.

PMID- 16815506
TI  - Medroxyprogesterone acetate attenuates long-term effects of 17beta-estradiol in
      coronary arteries from hyperlipidemic rabbits.
AB  - OBJECTIVE: The progestin component in hormone replacement treatment may oppose
      the effects of estrogen on vascular function. This study examined the effect of
      long-term treatment with 17beta-estradiol (E(2)) alone and in combination with
      two progestins on K(+) and Ca(2+)-mediated mechanisms in coronary arteries.
      METHODS: Watanabe heritable hyperlipidemic rabbits were treated orally with
      either E(2) (4 mg/day), medroxyprogesterone acetate (MPA) (10 mg/day),
      norethindrone acetate (NETA) (2 mg/day), E(2)+MPA, E(2)+NETA, or placebo for 16
      weeks (n=10 in each group). Coronary arteries were used for mRNA and myograph
      studies. RESULTS: E(2) increased vasodilatation induced by sodium nitroprusside
      and decreased vasocontraction induced by potassium. The first but not the latter
      response was opposed by MPA. The combination of MPA and E(2), but neither
      compound alone enhanced nimodipine-induced vasodilatation and increased the
      expression of L-type voltage-gated Ca(2+) channel mRNA. NETA had no opposing
      effects. Hormone treatment did not affect large-conductance Ca(2+) activated or
      ATP-sensitive K(+) channels or cGMP-dependent protein kinase mRNA expression.
      Hyperlipidemia had no effect on vascular reactivity. CONCLUSION: When E(2) is
      administered with MPA, effects of E(2) on nitric oxide and Ca(2+)-mediated
      vascular reactivity in rabbit coronary arteries are modulated. The results
      suggest that the progestin component in hormone replacement treatment may
      interfere with the supposed beneficial vascular effects of estrogen.

PMID- 16815508
TI  - Schlieren visualization of ultrasonic wave fields with high spatial resolution.
AB  - The visualization of ultrasonic wave fields in optically transparent liquids
      using the acousto-optic interaction is a well proven tool for the experimental
      investigation of wave propagation including wave field interaction effects with
      certain discontinuities and obstacles like reflection, refraction, and
      diffraction effects as well as for transducer testing and design. For high
      resolution visualization of wave fields including pulsed waveforms, pulsed light
      sources and sensitive optical imaging sensors with certain specifications are
      needed. In this paper the technical requirements of optical and electronic
      components for high resolution visualization of ultrasound wave fields will be
      presented. Also, specifications and operation results of a new designed,
      inexpensive Schlieren optical system will be presented, which is capable of
      pulsed wave field visualization in the MHz frequency range. The spatial
      resolution is high enough, not only for accurate beam shape and wave pattern
      visualization, but also for a gray-scaled display of wave amplitudes including
      amplitude zero crossings in ultrasound pulses. Consequently, ultrasonic
      wavelengths can be visualized quantitatively as well as wavelength changes of the
      ultrasound pulses while traveling through transparent media with different sound
      velocities. Results to be presented will include 2 MHz and 10 MHz experiments
      using single transducers as well as linear arrays of commercial medical scanners
      during their standard operation showing the system beamforming characteristics.

PMID- 16815509
TI  - Lamb mode reflections at the end of a plate loaded by a viscoelastic material.
AB  - This paper deals with a study of the conversion of a Lamb wave at the loaded edge
      of a plate. An experimental study is performed to know the interaction of surface
      waves with a viscoelastic material. A Lamb wave is generated by a wedge. At the
      end of the plate, this wave gives rise to several reflected waves. A first study
      makes it possible qualitatively to know the Lamb modes present in reflection.
      Secondly, conversion phenomena are studied to know if surface waves are sensitive
      to evolution in the time of the viscoelastic material structure. The selected
      material is a sol-gel containing silica.

PMID- 16815507
TI  - Subchronic chloroform priming protects mice from a subsequently administered
      lethal dose of chloroform.
AB  - Protection offered by pre-exposure priming with a small dose of a toxicant
      against the toxic and lethal effects of a subsequently administered high dose of
      the same toxicant is autoprotection. Although autoprotection has been extensively
      studied with diverse toxicants in acute exposure regimen, not much is known about
      autoprotection after priming with repeated exposure. The objective of this study
      was to investigate this concept following repeated exposure to a common water
      contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either
      vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30
      days, were challenged with a normally lethal dose of chloroform (750 mg
      chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed
      mice died between 48 and 96 h after administration of the lethal dose in contrast
      to 100% survival of mice primed with chloroform. Time course studies indicated
      lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice.
      Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of (14)C
      chloroform-derived radiolabel did not differ between livers of unprimed and
      primed mice after lethal dose exposure, indicating that protection in liver is
      neither due to decreased bioactivation nor increased detoxification. Kidney GSH
      and glutathione reductase activity were upregulated, with a concomitant reduction
      in oxidized glutathione in the primed mice following lethal dose challenge,
      leading to decreased renal covalent binding of (14)C-chloroform-derived
      radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine
      (BSO) intervention led to 70% mortality in primed mice challenged with lethal
      dose. These data suggest that higher detoxification may play a role in the lower
      initiation of kidney injury observed in primed mice. Exposure of primed mice to a
      lethal dose of chloroform led to 40% lower chloroform levels (AUC(15-360 min)) in
      the systemic circulation. Exhalation of (14)C-chloroform was unchanged in primed
      as compared to unprimed mice (AUC(1-6 h)). Urinary excretion of (14)C-chloroform
      was higher in primed mice after administration of the lethal dose. However,
      neither slightly higher urinary elimination nor unchanged expiration can account
      for the difference in systemic levels of chloroform. Liver and kidney
      regeneration was inhibited by the lethal dose in unprimed mice leading to
      progressive injury, organ failure, and 90% mortality. In contrast, sustained and
      highly stimulated compensatory hepato- and nephrogenic repair prevented the
      progression of injury resulting in 100% survival of primed mice challenged with
      the lethal dose. These findings affirm the critical role of tissue regeneration
      and favorable detoxification (only in kidney) of the lethal dose of chloroform in
      subchronic chloroform priming-induced autoprotection.

PMID- 16815510
TI  - Fast beating null strip during the reflection of pulsed Gaussian beams incident
      at the Rayleigh angle.
AB  - It is well known that harmonic bounded Gaussian beams undergo a transformation
      into two bounded beams upon reflection on a solid immersed in a liquid. The
      effect is known as the Schoch effect and can be found at the Rayleigh angle for
      thick plates and at the different Lamb angles for thin plates. Here, a study is
      made on the effect of pulsed Gaussian beams reflected on solids. It is found
      experimentally that the Rayleigh wave phenomenon still generates two reflected
      bounded beams, whereas Lamb wave phenomena do not generate this effect. This fact
      may be explained intuitively by realizing that the Rayleigh phenomenon is a
      coincidental phenomenon that is generated in situ, whereas the Lamb wave
      phenomenon is a non-coincidental phenomenon that is generated only after incident
      sound is influenced by both sides of a thin plate. Another explanation is the
      fact that Rayleigh waves are not dispersive, whereas stimulation and propagation
      of Lamb waves is frequency dependent. A pulse contains many frequencies and
      therefore only a fraction of the incident pulse is transformed into a Lamb wave.
      In this paper, numerical simulations are performed that show that actually the
      Schoch effect does occur neither for Rayleigh waves, nor for Lamb waves. As a
      matter of fact, a pulse, incident at the Rayleigh angle, generates two reflected
      lobes with a null zone of a different kind. The null zone is beating several
      times during the passage of each pulse. This results in a 'null zone' having a
      lower mean intensity than any of the two lobes, still less outspoken than for the
      case of harmonic incident bounded beams. This effect does only occur for Rayleigh
      wave generation and is much less outspoken for Lamb wave generation.

PMID- 16815512
TI  - Treatment of hyperactive children: increased efficiency through modifications of
      homeopathic diagnostic procedure.

PMID- 16815513
TI  - Q/LM potencies: historical reasons for the long delay in their recognition.

PMID- 16815514
TI  - Double-blind, placebo-controlled homeopathic pathogenetic trials: symptom
      collection and analysis.
AB  - BACKGROUND: Homeopathic pathogenetic trials (provings) are fundamental to
      homeopathy. Since most of the data from available provings have not been
      statistically evaluated, it is unclear how specific reported symptoms are and how
      they differ from those reported by people taking placebo. METHOD: We combine and
      analyse data from two different homeopathic pathogenic trials--including 10 and
      11 provers, respectively, and both including 30% placebo-to test the null
      hypothesis that there is no significant difference between the number of symptoms
      in placebo and verum groups. RESULTS: The principal results were: Placebo
      reported less symptoms than verum groups. Symptom distribution according to
      predefined classes (common symptoms increased in intensity and/or duration-,
      cured, old, new and exceptional) was statistically different between placebo and
      verum group at a high level of significance (P<0.001). Compared to verum, placebo
      provers reported less new and old but more common (increased in duration or
      intensity) symptoms. Within repertory categories, other differences were
      detected. The two groups differ in terms of the duration of each symptom and
      kinetics of symptoms: most symptoms were more persistent in verum than in placebo
      groups and verum provers recorded a decreasing number of symptoms with time.
      Placebo provers did not show such a temporal pattern. CONCLUSIONS: If confirmed
      by other studies these results would demonstrate the non-equivalence between
      homeopathic medicines in high dilution and placebo and contribute to the
      improvement of proving methodology and evaluation.

PMID- 16815515
TI  - Effect of a Homeopathic complex on oestrus induction and hormonal profile in
      anoestrus cows.
AB  - This study was undertaken to evaluate the efficacy of a homeopathic complex in
      the management of true anoestrus in crossbred cows. Six anoestrus cows were
      treated with a homeopathic complex (Calcarea phosphorica 30c, Aletris farinosa
      30c, Pulsatilla 30c, Aurum muriaticum natronatum 30c, Sepia 30c and Phosphorus
      30c in equal proportion, 15 pills twice daily orally for 10 days). Six animals
      acted as control without any treatment. Treatment was 100% effective in inducing
      oestrus in anoestrus cows with mean interval of 27.5+/-5.3 days. All animals
      conceived and overall conception rate was 54.5% with 1.83 services per
      conception. In the homeopathic complex treated group, increased serum oestradiol
      concentration (20.88+/-5.60 to 27.80+/-7.28 pg/ml) was observed compared to the
      pretreatment (11.71+/-2.06 pg/ml) and control value (10.43+/-1.77 to 13.94+/-3.14
      pg/ml). The homeopathic complex medicine may be effective and economical in the
      treatment of true anoestrus condition in cows.

PMID- 16815516
TI  - Therapeutic and pathogenetic animal models for Dolichos pruriens.
AB  - The therapeutic and pathogenetic effects of Dolichos pruriens were evaluated
      using experimental models in rats. In the therapeutic experiment Wistar rats were
      housed in a heated environment (25+/-3 degrees C) to induce itch, and treated
      with ascending potencies D. pruriens (6 cH, 9 cH, 12 cH and 30 cH), each for 10
      days. The positive control group received vehicle (ethanol 30% in water). The
      negative control group received no treatment and were kept at a standard
      temperature. In the pathogenetic experiment, all animals were kept at a
      temperature of 20+/-3 degrees C and treated for 30 consecutive days with D.
      pruriens 6 or 30 cH, or ethanol vehicle, or no treatment. The experiments were
      performed blind. The statistical analysis used Bartlett's test, followed by
      ANOVA/Tuckey-Krammer or Kruskal-Wallis/Dunn. The results point to the existence
      of therapeutic effects, with inhibition of the itching, skin lesions and fur
      thinning produced by heat, more evident in later observations, with the 9 12, and
      30 cH potencies (Kruskal-Wallis/Dunn; P=0.001). No changes were observed in the
      other parameters, such as open field activity and laterality of the itching. In
      the pathogenetic experiment, no changes were observed in any parameters examined.
      We conclude that the proposed experimental model demonstrates the therapeutic
      effect of D. pruriens, but not its pathogenetic effects.

PMID- 16815517
TI  - Amelioration of root-knot disease of lady's finger plants by potentized Cina and
      Santonin.
AB  - Lady's finger plants (Hibiscus esculentus), grown in pots, were inoculated with
      the second-stage larvae (76+/-6) of root-knot nematodes Meloidogyne incognita,
      starting 7 days later they were treated with Cina 30c, Santonin 30c or Ethanol
      30c by foliar spray for 10 consecutive days. The drugs in 90% ethanol were
      diluted with distilled water 1:1000 before application on plants. Thirty days
      after the last treatment the plants were uprooted. Cina 30c and Santonin 30c
      reduced nematode infestation of plants significantly in terms of root-gall
      number, root-protein content and nematode population in roots. Santonin 30c
      reduced root water content. Santonin 30c may have influenced the water channel
      proteins of root tissues thereby altering the water contents of roots. The
      reduced water content in roots might have adversely affected the root-knot
      nematodes and thus reduced nematode infestation. Ethanol 30c also has some effect
      on treated plants.

PMID- 16815518
TI  - Effect of fortification of Mulberry leaves with homeopathic drug Nux vomica on
      Bombyx mori. L.
AB  - Silk worm (Bombyx mori L.) larvae were fed on Mulberry leaves treated with Nux
      vomica mother tincture. The impact on larval, cocoon, shell and pupal weight,
      silk ratio, average filament length and denier, and number of breakages during
      reeling were investigated. The results were positive in all parameters under
      study except cocoon weight, pupal weight, and the average denier of the filament.

PMID- 16815519
TI  - Homeopathy for anxiety and anxiety disorders: a systematic review of the
      research.
AB  - OBJECTIVE: To conduct a systematic review of the clinical research evidence on
      homeopathy in the treatment of anxiety and anxiety disorders. METHODS: A
      comprehensive search of major biomedical databases: MEDLINE, EMBASE, ClNAHL,
      PsycINFO, Cochrane Library; and of specialist complementary and alternative
      medicine (CAM) databases: AMED, CISCOM and Hom-Inform was conducted. Efforts were
      made to identify unpublished and ongoing research using relevant sources and
      experts in the field. Relevant research was categorised by study type and
      appraised according to study design. Clinical commentaries were obtained for
      studies reporting clinical outcomes. RESULTS: Eight randomised controlled studies
      were identified. The types of anxiety and anxiety disorders studied were test
      anxiety, generalised anxiety disorder and anxiety related to medical or physical
      conditions such as cancer or surgical procedures. Single case reports/studies
      were the most frequently encountered study type but other study types including
      uncontrolled trials/case series and surveys were also found. No relevant
      qualitative research was identified. CONCLUSIONS: A comprehensive search
      demonstrates that the evidence on the benefit of homeopathy in anxiety and
      anxiety disorders is limited. A number of studies of homeopathy in such
      conditions were located but the randomised controlled trials report contradictory
      results, are underpowered or provide insufficient details of methodology. Several
      uncontrolled and observational studies reported positive results including high
      levels of patient satisfaction but because of the lack of a control group, it is
      difficult to assess the extent to which any response is due to homeopathy.
      Adverse effects reported appear limited to 'remedy reactions' and included
      temporary worsening of symptoms and reappearance of old symptoms. On the basis of
      this review it is not possible to draw firm conclusions on the efficacy or
      effectiveness of homeopathy for anxiety. However, surveys suggest that homeopathy
      is quite frequently used by people suffering from anxiety. If shown to be
      effective, it is possible that homeopathy may have benefits in terms of adverse
      effects and acceptability to patients. Consequently, further investigation is
      indicated. Future research should be of pragmatic design and include qualitative
      studies.

PMID- 16815520
TI  - Treatment of hyperactive children: increased efficiency through modifications of
      homeopathic diagnostic procedure.
AB  - BACKGROUND: The rigorous test to which homeopathy was subject in our recent
      double-blind clinical trail of homeopathic treatment of attention deficit
      hyperactivity disorder (ADHD) necessitated optimized treatment meeting the
      highest standards. METHODS: Optimization was performed in three steps: (1) In
      successfully treated children, prescriptions leading to an insufficient response
      were analysed by a general questionnaire to identify unreliable symptoms. (2)
      Polarity analysis, a further development of Bonninghausen's concept of
      contraindications, was introduced in response to the frequently one-sided
      symptoms. This enabled us to use few but specific symptoms to identify the
      medicine whose genius symptoms exhibit the closest match to the patient's
      characteristic symptoms. (3) We investigated the influence of the primary
      perception symptoms on the result of the repertorization. Perception symptoms are
      not normally recorded during a patient interview even though they are among the
      most reliable facts related by the patients. At the same time we were able to
      improve the continuity of improvement of ADHD symptoms using liquid Q-potencies.
      RESULTS: Introducing the questionnaire, polarity analysis, and including
      perception symptoms, lead to an improvement in the success rate of the first
      prescription from 21% to 54%, of the fifth prescription from 68% to 84%.

PMID- 16815521
TI  - Hahnemann's experiments with 50 millesimal potencies: a further review of his
      casebooks.
AB  - BACKGROUND: A review of Hahnemann's clinical records at the Institute for History
      of Medicine of the Robert Bosch Foundation in Stuttgart shows that until the end
      of his life, Hahnemann continued to refine his clinical method, based on clinical
      cases. His "most perfected method" motivated him to write the sixth edition of
      the The Organon of the Healing Art, proposing solutions controlling the side
      effects he observed with repeated doses of homeopathic medicines. Unfortunately,
      this was published many years posthumously. The sixth edition of The Organon
      introduced the fifty-millesimal scale. OBJECTIVES: To identify the clinical cases
      treated with fifty-millesimal potencies and analyze Hahnemann's use of them.
      RESULTS: 1836 prescriptions of fifty-millesimal potencies were found, between
      1837 and 1843 in three phases: initially sporadic; later compared regularly to
      centesimal dynamizations; and finally systematically. Thirty five medicines were
      identified in fifty-millesimal prescriptions, seven in potencies higher than 10
      and only 3 (Sulphur, Mercurius solubilis and Rhus toxicodendron) used in the 30th
      degree. This accords with Haehl's information about the remedies in Hahnemann's
      case of fifty-millesimal potencies. CONCLUSIONS: Hahnemann probably decided to
      write the sixth edition, in 1840, to incorporate his latest experience with the
      repetition of potentized doses and periodically modified potencies. He must have
      revised it after February 1842 to include his latest findings with fifty
      millesimal potencies in ascending degrees. Hahnemann's conception about the
      superiority of the fifty-millesimal in comparison with the centesimal
      dynamization was based on a significant number of experiments with the two
      scales.

PMID- 16815522
TI  - Strange, rare and peculiar: aborigines, Benedictines and homeopathy.

PMID- 16815523
TI  - 20 years ago: the British Homoeopathic Journal, July 1986.

PMID- 16815524
TI  - Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus
      replication.
AB  - All coronaviruses encode a small hydrophobic envelope (E) protein, which mediates
      viral assembly and morphogenesis by an unknown mechanism. We have previously
      shown that the E protein from Severe Acute Respiratory Syndrome coronavirus (SARS
      CoV) forms cation-selective ion channels in planar lipid bilayers (Wilson, L.,
      McKinlay, C., Gage, P., Ewart, G., 2004. SARS coronavirus E protein forms cation
      selective ion channels. Virology 330(1), 322-331). We now report that three other
      E proteins also form cation-selective ion channels. These E proteins were from
      coronaviruses representative of taxonomic groups 1-3: human coronavirus 229E
      (HCoV-229E), mouse hepatitis virus (MHV), and infectious bronchitis virus (IBV),
      respectively. It appears, therefore, that coronavirus E proteins in general,
      belong to the virus ion channels family. Hexamethylene amiloride (HMA)--an
      inhibitor of the HIV-1 Vpu virus ion channel--inhibited the HCoV-229E and MHV E
      protein ion channel conductance in bilayers and also inhibited replication of the
      parent coronaviruses in cultured cells, as determined by plaque assay.
      Conversely, HMA had no antiviral effect on a recombinant MHV with the entire
      coding region of E protein deleted (MHVDeltaE). Taken together, the data provide
      evidence of a link between inhibition of E protein ion channel activity and the
      antiviral activity of HMA.

PMID- 16815525
TI  - Groundbreaking papers in Water Research 1967-2006. A dynamic model of the
      clarification-thickening process.

PMID- 16815526
TI  - Soil organic matter-hydrogen peroxide dynamics in the treatment of contaminated
      soils and groundwater using catalyzed H2O2 propagations (modified Fenton's
      reagent).
AB  - The interactions between catalyzed H(2)O(2) propagations (CHP-i.e. modified
      Fenton's reagent) and soil organic matter (SOM) during the treatment of
      contaminated soils and groundwater was studied in a well-characterized surface
      soil. The fate of two fractions of SOM, particulate organic matter (POM) and
      nonparticulate organic matter (NPOM), during CHP reactions was evaluated using
      concentrations of hydrogen peroxide from 0.5 to 3M catalyzed by soluble iron
      (III), an iron (III)-ethylenediamine tetraacetic acid (EDTA) chelate, or
      naturally-occurring soil minerals. The destruction of total SOM in CHP systems
      was directly proportional to the hydrogen peroxide dosage, and was significantly
      greater at pH 3 than at neutral pH; furthermore, SOM destruction occurred
      predominantly in the NPOM fraction. At pH 3, SOM did not affect hydrogen peroxide
      decomposition rates or hydroxyl radical activity in CHP reactions. However, at
      neutral pH, increasing the mass of SOM decreased the hydrogen peroxide
      decomposition rate and increased the rate of hydroxyl radical generation in CHP
      systems. These results show that, while CHP reactions destroy some of the organic
      carbon pools, SOM does not have a significant effect on the CHP treatment of
      soils and groundwater.

PMID- 16815527
TI  - Efficient and stable nitritation and denitritation of ammonium-rich sludge
      dewatering liquor using an SBR with continuous loading.
AB  - Separate treatment of dewatering liquor from anaerobic sludge digestion
      significantly reduces the nitrogen load of the main stream and improves overall
      nitrogen elimination. Such ammonium-rich wastewater is particularly suited to be
      treated by high rate processes which achieve a rapid elimination of nitrogen with
      a minimal COD requirement. Processes whereby ammonium is oxidised to nitrite only
      (nitritation) followed by denitritation with carbon addition can achieve this.
      Nitrogen removal by nitritation/denitritation was optimised using a novel SBR
      operation with continuous dewatering liquor addition. Efficient and robust
      nitrogen elimination was obtained at a total hydraulic retention time of 1 day
      via the nitrite pathway. Around 85-90% nitrogen removal was achieved at an
      ammonium loading rate of 1.2 kg [corrected] NH(4)(+)-N m(-3)d(-1). Ethanol was
      used as electron donor for denitritation at a ratio of 2.2 g COD g(-1) N removed.
      Conventional nitritation/denitritation with rapid addition of the dewatering
      liquor at the beginning of the cycle often resulted in considerable nitric oxide
      (NO) accumulation during the anoxic phase possibly leading to unstable
      denitritation. Some NO production was still observed in the novel continuous
      mode, but denitritation was never seriously affected. Thus, process stability can
      be increased and the high specific reaction rates as well as the continuous
      feeding result in decreased reactor size for full-scale operation.

PMID- 16815528
TI  - Leaching and degradation of 21 pesticides in a full-scale model biobed.
AB  - Filling and cleaning of pesticide sprayers presents a potential risk of pollution
      of soil and water. Three different solutions for handling sprayers have been
      suggested: Filling and cleaning in the field, filling and cleaning on hard
      surfaces with collection of the waste water, and filling and cleaning on a
      biobed, which is an excavation lined with clay and filled with a mixture of
      chopped straw, sphagnum and soil with turf on top, and with increased sorption
      capacity and microbial activity for degradation of the pesticides. In the present
      study the degradation and leaching of 21 pesticides (5 g of each) was followed in
      an established full-scale model biobed. Percolate was collected and analysed for
      pesticide residues, and the biobed material was sampled at three different depths
      and analysed by liquid chromatography double mass spectrometry (LC-MSMS). During
      the total study period of 563 days, no traces of 10 out of 21 applied pesticides
      were detected in the percolate (detection limits between 0.02 and 0.9 microg l(
      1)) and three pesticides were only detected once and at concentrations below 2
      microg l(-1). During the first 198 days before second application, 14% of the
      applied herbicide bentazone was detected in the leachate with maximum and mean
      concentrations of 445 and 172 microg l(-1), respectively. About 2% of the initial
      mecoprop and fluazifop dose was detected in the percolate, with mean
      concentrations of 23 microg l(-1), while MCPA and dimethoate had mean
      concentrations of 3.5 and 4.7 microg l(-1), respectively. Leachate concentrations
      for the remaining pesticides were generally below the detection limit (0.02-0.9
      microg l(-1), below 1% of applied). Sorption studies of five pesticides showed
      that compounds with a low K(d) value appeared in the leachate. After 169 days,
      all pesticides in the biobed profile were degraded to a level below 50% of the
      calculated initial dose. Pesticides with K(oc) values above 100 were primarily
      found in the uppermost 10 cm and degraded slowest due to the low bioavailability.
      The 11 most degradable pesticides were all degraded such that less than 3%
      remained in the biobed after 169 days. Following second pesticide application of
      the biobed, leachate was sampled 215 and 365 days after the treatment. This
      showed the same pesticides to be leached out and at concentrations comparable to
      those of the first treatment. The same pesticides as after the first treatment
      were retained in the biobed.

PMID- 16815529
TI  - Revised stratigraphy of Area 123, Koobi Fora, Kenya, and new age estimates of its
      fossil mammals, including hominins.
AB  - Recent geologic study shows that all hominins and nearly all other published
      mammalian fossils from Paleontological Collection Area 123, Koobi Fora, Kenya,
      derive from levels between the KBS Tuff (1.87+/-0.02 Ma) and the Lower Ileret
      Tuff (1.53+/-0.01 Ma). More specifically, the fossils derive from 53 m of section
      below the Lower Ileret Tuff, an interval in which beds vary markedly laterally,
      especially those units containing molluscs and algal stromatolites. The upper
      Burgi Member (approximately 2.00-1.87 Ma) crops out only in the southwestern part
      of Area 123. Adjacent Area 110 contains larger exposures of the member, and there
      the KBS Tuff is preserved as an airfall ash in lacustrine deposits and also as a
      fluvially redeposited ash. We observed no mammalian fossils in situ in this
      member in Area 123, but surface specimens have been documented in some
      monographic treatments. Fossil hominins from Area 123 were attributed to strata
      above the KBS Tuff in the 1970s, but later they were assigned to strata below the
      KBS Tuff (now called the upper Burgi Member). This study definitively places the
      Area 123 hominins in the KBS Member. Most of these hominins are between 1.60 and
      1.65 myr in age, but the youngest may date to only 1.53 Ma, and the oldest, to
      1.75 Ma. All are 0.15-0.30 myr younger than previously estimated. The new age
      estimates, in conjunction with published taxonomic attributions of fossils,
      suggest that at least two species of Homo coexisted in the region along with A.
      boisei until at least 1.65 Ma. Comparison of crania KNM-ER 1813 and KNM-ER 1470,
      which were believed to be of comparable age, is at the focus of the debate over
      whether Homo habilis sensu lato is in fact composed of two species: Homo habilis
      and Homo rudolfensis. These two crania are separated in time by approximately
      0.25 myr, and therefore, arguments for their conspecificity no longer need to
      confront the issue of unusually high contemporaneous variation within a single
      species.

PMID- 16815530
TI  - Growth of Agropyron elongatum in a simulated nickel contaminated soil with lime
      stabilization.
AB  - A greenhouse study was performed to evaluate the feasibility of using Agropyron
      elongatum and lime treatment for remediation of a simulated nickel (Ni)
      contaminated acidic soil. The acid soil was spiked with four levels of Ni, i.e.,
      0, 15, 50, and 100 mg Ni kg(-1) soil and the soil pH at each Ni level was
      adjusted to 4, 6 and 8 by liming with CaO. Addition of lime raised the soil pH
      and resulted in a decrease in concentrations of DTPA-extractable and water
      soluble Ni in the soil, with a maximum reduction of 64 and 28 mg kg(-1),
      respectively at the highest level of Ni treatment as compared to the control
      without Ni treatment. In general, excessive Ni content in soil, especially at pH
      4 inhibited the growth of Agropyron. Liming improved the growth condition and the
      highest dry weight yield of 12 g pot(-1) was obtained in soil spiked with 15 mg
      Ni kg(-1) at pH 6; and at the highest level of Ni, the dry weight yield increased
      from 0.48 to 5.96 g pot(-1) when the pH was increased from 4 to 6. However a
      further increase in pH to 8 did not improve plant yield because of the
      unavailability of nutrients at such a high pH. Nickel contents in plant were
      positively correlated to soil Ni contents at each respective pH level. Most of
      the Ni taken up by Agropyron was retained in the roots and the highest Ni uptake
      by plant was 3.9 mg pot(-1) in soil spiked with 100 mg Ni kg(-1) at pH 5.9, which
      was about 2.6% of total Ni added to the soil. This implies that Agropyron is not
      a hyperaccumulating species but is highly tolerant. Lime amendment together with
      the tolerant characteristic of Agropyron could provide a possible means to
      remediate Ni contaminated soils through phytostabilization.

PMID- 16815531
TI  - Detection of the marine toxin okadaic acid in mussels during a diarrhetic
      shellfish poisoning (DSP) episode in Thermaikos Gulf, Greece, using biological,
      chemical and immunological methods.
AB  - An approach involving chemical and biological techniques was taken for the
      detection and quantification of the marine toxin okadaic acid (OA) in mussels
      from Thermaikos Gulf, Greece, during a 4-month DSP episode that occurred in 2002.
      Samples were analyzed using the mouse bioassay, high performance liquid
      chromatography (HPLC) with fluorimetric detection and an enzyme-linked
      immunosorbent assay (ELISA). Okadaic acid was quantifiable at three different
      sites of Thermaikos Gulf reaching a maximum concentration of 36 microg/g
      hepatopancreas. High correlation was revealed between results derived from HPLC
      and ELISA (R2=0.998), while 91% consistency between HPLC and the mouse bioassay
      results was observed.

PMID- 16815532
TI  - Mercury in fish available in supermarkets in Illinois: are there regional
      differences.
AB  - Media coverage has made the public aware of both the benefits and the risks from
      eating self-caught fish, but information on contaminants in commercial fish is
      much more limited, especially on a local level. The U.S. Food and Drug
      Administration website provides methylmercury data for a variety of fish, but for
      many species sample sizes are small and data are more than a decade old, whereas
      commercial fish sources are highly dynamic. A few state agencies are beginning to
      provide contaminant information for commercial fish, including canned tuna. We
      examined the mercury concentration of six types of fish purchased in supermarkets
      in Chicago, Illinois in 2005. We measured total mercury (methylmercury accounts
      for about 90% of the total mercury in fish). One key question was whether the
      concentrations of mercury in fish available locally were similar to those
      reported in other areas of the country and in the FDA U.S. national data base.
      Such information is critical for the public, especially pregnant women or those
      planning on pregnancy, making decisions about types and quantities of fish to
      consume. Some fish are available generally throughout the U.S., but others are
      more locally available, suggesting a need for site-specific information. This
      research was stakeholder driven, and reflected local interest in the safety of
      local fish. There were significant differences in mercury concentrations among
      the fish, ranging from a mean of 0.03 microg/g (ppm-wet weight) for salmon (Salmo
      spp.) to 1.41 ppm for swordfish (Xiphias gladius). Maximum values for three
      species of fish (orange roughy Hoplostethus atianticus, swordfish walleye Sander
      vitreus) were over 1 ppm (FDA action level), and all of the fish except salmon
      had some values above 0.5 ppm, the action level set by some states and countries.
      There were significant differences in mercury concentrations among three types of
      canned tuna (Thunnus spp): "gourmet tuna" had the least amount of mercury, and
      white tuna had the most. The mean concentrations reported in this study were
      generally similar to those reported by the FDA, but there were important
      differences: 1) although the mean mercury concentrations for orange roughy for
      the Chicago data was similar to the FDA data, the maximum concentration was
      higher; 2) the mean for the Chicago swordfish was higher than the FDA data (1.26
      vs 0.97 ppm, methylmercury); 3) the maximum for tuna steaks was higher in the FDA
      data set; and, 4) mean values for grouper (Epinephelus spp.) were higher in the
      FDA data set than the Chicago data. Further, the FDA has virtually no data on
      walleye and none on "gourmet tuna". These conclusions suggest that there are
      enough variations between the local data (Chicago) and the FDA data to warrant
      periodic local monitoring of commercial fish to provide up-to-date information to
      consumers about mercury in the fish they eat.

PMID- 16815533
TI  - Considerations on the sample size of wood mice used to biomonitor metals.
AB  - The concentrations of various metals (Zn, Cu, Mn and Cr) in liver, kidneys and
      brain from specimens of the wood mouse Apodemus sylvaticus captured from 5 sites
      were measured. Two of the sites were in a restored mine dump, another in an area
      characterized by serpentized soils and the remaining two were control sites. The
      sample size required for statistical differentiation of the sampling sites was
      calculated from the mean values and the variability in bioaccumulation
      corresponding to each of the sites. The relationship between the sample size and
      the results of the statistical test used to reveal significant differences
      between the mean concentrations of metals in organs from A. sylvaticus is
      demonstrated. The homeostatic control exerted by the wood mice on the tissue
      levels of metals reduced the interpopulational variability, thereby homogenizing
      the mean bioaccumulation corresponding to the different sampling stations. The
      sample size, tissue regulation of the levels of heavy metals and the patterns of
      variability are of vital importance in evaluating the usefulness of A. sylvaticus
      as a biomonitor of heavy metals.

PMID- 16815534
TI  - Heterogeneous gonadotropin-releasing hormone receptor expression in ovarian
      granulosa cell tumors.

PMID- 16815535
TI  - Association between cigarette smoking and prognosis in locally advanced cervical
      carcinoma treated with chemoradiation: a Gynecologic Oncology Group study.
AB  - OBJECTIVE: To determine if smoking, a known risk factor for a number of cancers
      including cervical cancer, is associated with poor prognosis in patients with
      locally advanced cervical carcinoma treated with chemoradiation. METHODS:
      Patients with primary, previously untreated, histologically confirmed stage II-B,
      III-B or IV-A cervical carcinoma participated in a Gynecologic Oncology Group
      (GOG) phase III study (GOG 165) and were randomly allocated to receive radiation
      plus either cisplatin or 5-fluorouracil. Smoking behavior was ascertained using
      an administered questionnaire and by quantifying urine cotinine concentration.
      Disease progression was defined as a >or=50% increase in the cross product of the
      existing tumor compared with previous assessments. Patients were followed until
      death. RESULTS: Of 328 enrolled patients, 12 were ineligible, one was inevaluable
      for reported smoking status and 40 others were inevaluable for cotinine-derived
      smoking status. Among evaluable patients, 133 (42%) were reported smokers and 111
      (40%) were cotinine-derived smokers. The kappa for agreement between the groups
      was 0.872 (P<0.01). Compared with non-smokers, median survival was 15 months
      shorter for reported smokers and 20 months shorter for cotinine-derived smokers
      (P<0.01). After adjusting for covariates, a significant increase in the risk of
      death (but not disease progression) was observed for reported smokers (hazard
      ratio [HR]: 1.51; 95% confidence interval [CI]: 1.01-2.27; P=0.04) and cotinine
      derived smokers (HR: 1.57; 95% CI: 1.03-2.38; P=0.04). CONCLUSIONS: Smoking
      predicts worse overall survival in women with locally advanced cervical carcinoma
      treated with chemoradiation.

PMID- 16815536
TI  - Incidence and management of pleural effusions after diaphragm peritonectomy or
      resection for advanced mullerian cancer.
AB  - OBJECTIVES: Diaphragm peritonectomy or resection is an effective way to
      cytoreduce diaphragm disease but frequently results in sympathetic pleural
      effusions. Our objective was to determine the incidence and management of
      effusions that developed after diaphragm surgery in patients with advanced
      mullerian cancer. METHODS: We reviewed the records of all patients with stage
      IIIC-IV epithelial ovarian, fallopian tube, or peritoneal cancer who had
      diaphragm peritonectomy or resection as part of optimal primary cytoreduction at
      our institution from 2000-2003. All patients had preoperative and serial
      postoperative chest X-rays to detect and follow pleural effusions. Factors
      evaluated included the presence and size of preoperative and postoperative
      effusions, their laterality, and subsequent need for thoracentesis and/or chest
      tube placement for symptomatic effusions. RESULTS: Of the 215 patients who had
      primary cytoreduction during the study period, 59 (27%) underwent diaphragm
      peritonectomy or resection. In addition to standard cytoreduction, 31 (53%) of
      these 59 patients had diaphragm surgery alone, while 28 (47%) had diaphragm
      surgery in combination with other upper abdominal resections. Laterality of
      diaphragm surgery was as follows: right only, 43 (73%); left only, 2 (3%); and
      bilateral, 14 (24%). Intraoperative chest tubes were placed in 7 (12%) patients.
      In the remaining 12 patients with preoperative effusions, postoperative effusions
      on the same side as the diaphragm surgery increased in 6 patients (50%), and 3
      patients (25%) required postoperative thoracentesis or chest tube. In the
      remaining 40 patients without preoperative effusions, ipsilateral effusions
      developed in 24 patients (60%), and 5 patients (13%) required postoperative chest
      tubes. The overall rate of new or increased ipsilateral effusions was 58%; the
      overall rate of postoperative thoracentesis or chest tube placement was 15%. In
      75% of the patients, thoracentesis or chest tubes were placed within 5 days of
      surgery (median, 3 days; range, 2-24). CONCLUSIONS: More than half of patients
      developed ipsilateral pleural effusions after diaphragm peritonectomy for
      cytoreduction. Most were managed conservatively without requiring a chest tube or
      thoracentesis. The incidence of symptomatic effusions was not high enough to
      recommend routine chest tube placement at the time of diaphragm peritonectomy or
      resection.

PMID- 16815537
TI  - Potential underdosing of carboplatin in gynecological malignancies.

PMID- 16815538
TI  - HPV, cervical dysplasia and anal cancer screening--a need for liaison between
      gynecology and colorectal clinics.

PMID- 16815540
TI  - The effects of ovarian function on estrus synchronization with PGF in dairy cows.
AB  - Milk progesterone concentration (P4), milk yield, milk composition, ovarian
      structures and pregnancy status were studied in 108 cows treated with two doses
      of PGF 14 days apart and inseminated at fixed time (TAI) 80-82 h later. The
      synchronization protocol was started at 70+/-1.4 days after parturition. Milk P4
      profiles revealed that anestrus, failure of luteolysis following treatment with
      PGF and failure to ovulate following luteolysis were the main reasons for low
      pregnancy rate with TAI. Anestrous cows had a higher percentage of milk fat
      (P<0.05) and higher fat to protein ratio (P<0.01), and cows that did not undergo
      luteolysis had higher milk yield (P<0.05) and lower percentage of milk protein
      (P<0.05) than cows that responded to PGF treatment. Cows that did not undergo
      luteolysis and cows that did not ovulate following luteolysis had lower milk P4
      during the luteal phase preceding the second PGF injection (P<0.01 and P<0.05,
      respectively). Pregnancy rates 24 and 47 days after TAI in cows that responded as
      expected to the synchronization treatment were 62% and 54%, respectively.
      Pregnancy was precluded in non-responsive cows. The largest follicle at the time
      of TAI in cows experiencing late embryonic mortality was smaller (P=0.02) than in
      cows that successfully maintained pregnancy. Results suggest that a primary
      reason for low pregnancy rate in dairy cows after administration of PGF and TAI
      is inappropriate ovarian function prior to, or following treatment.

PMID- 16815539
TI  - Adolescent rats are protected from the conditioned aversive properties of cocaine
      and lithium chloride.
AB  - In humans, most drug use is initiated during adolescence and adolescent users are
      more likely to become drug-dependent than adult users. Repeated, high levels of
      use are required for the transition from use to addiction. Individual levels of
      drug use are thought to result from a balance between the pleasant or rewarding
      and the unpleasant or aversive properties of the drug. Repeated high levels of
      drug use are required for the transition from drug use to dependence. We
      hypothesized that diminished aversive effects of drugs of abuse during
      adolescence might be one reason for higher rates of use and addiction during this
      phase. We therefore tested adolescent and adult CD rats in single-dose cocaine
      conditioned taste aversion (CTA) at a range of doses (10-40 mg/kg), and examined
      whether various behavioral markers of addiction vulnerability were correlated to
      outcome in cocaine CTA. We found that adolescents are indeed less susceptible to
      cocaine CTA. In fact, age was the predominant predictor of CTA outcome,
      predominating over measures of novelty-seeking, anxiety, and stress hormone
      levels, which are all known to be related to drug intake in other models.
      Furthermore, we found that adolescent rats are also less susceptible to
      conditioned taste aversion to a low dose of a non-addictive substance, lithium
      chloride. These results suggest that one explanation for elevated drug use and
      addiction among adolescents is reduced aversive or use-limiting effects of the
      drugs. This contributes to our understanding of why adolescence is a particularly
      vulnerable period for development of drug abuse.

PMID- 16815541
TI  - Comparison of sperm quality of Belgian Blue and Holstein Friesian bulls.
AB  - Few data are currently available on sperm quality of Belgian Blue (BB) bulls. The
      present study compared sperm quality of BB to Holstein Friesian (HF) bulls of
      several age categories, by means of a classical semen evaluation. Volume and
      concentration, and consequently total sperm output depended largely on age.
      Gross, total, and progressive motility, % live and % normal spermatozoa were
      significantly lower in the BB breed. Primary sperm abnormalities, such as nuclear
      vacuoles, midpiece defects and cytoplasmic droplets which were noticed most
      frequently, occurred far more in the BB breed. Hence, disturbances in
      spermiogenesis are deemed to be the cause of the poorer BB sperm quality. Since
      these sperm abnormalities occur significantly more in the BB breed than in the HF
      breed, it seems as if the BB breed is genetically predisposed to a higher
      susceptibility to environmental stresses which are known to interfere with normal
      spermiogenesis. The small scrota typical of the inbred BB breed might in part be
      responsible for this, and therefore selection for larger scrota in the BB breed
      is advisable.

PMID- 16815542
TI  - Italian developmental dyslexic and proficient readers: where are the differences?
AB  - Italian dyslexic children are characterized by a pervasive reading speed deficit,
      with relatively preserved accuracy. This pattern has been associated with
      predominant use of the nonlexical reading procedure. However, there is no
      evidence of a deficit in the lexical route of Italian dyslexics. We investigated
      both lexical and nonlexical reading procedures in dyslexic children through two
      marker effects, namely, the word frequency effect and the effect of contextual
      grapheme-to-phoneme conversion rules. Although dyslexics were slower and less
      accurate than controls, they were affected by word frequency, grapheme
      contextuality, and their interaction in a similar manner as average readers.
      These results show the use of lexical reading in Italian dyslexics, and refute
      the claim of a deficit in whole-word processing with consequent over-reliance on
      the nonlexical route.

PMID- 16815543
TI  - Inhibitory kinetics of mercuric ion on the activity of beta-N-acetyl-D
      glucosaminidase from green crab (Scylla serrata).
AB  - Chemical modification of p-chloromercuribenzoate (PCMB) on beta-N-acetyl-d
      glucosaminidase (NAGase, EC 3.2.1.52) from green crab (Scylla serrata) has been
      studied. The results show that sulfhydryl group is essential for the activity of
      the enzyme. Inhibitory kinetics of the enzyme by mercuric chloride (HgCl2) has
      been studied using the kinetic method of the substrate reaction during inhibitor
      of enzyme. The kinetic results show that the inhibition of the enzyme by mercuric
      ion (Hg2+) at lower than 1.0 microM is a reversible reaction with residual
      activity and the inhibition belongs to be competitive. The inhibition kinetics
      model of Hg2+ on the enzyme was set up and the microscopic rate constants were
      determined and the data obtained were well fitted with the model. It was also
      turned out that only one molecule of HgCl2 binds to the enzyme molecule to lead
      the enzyme lose its activity. The above results suggest that the cysteine residue
      is essential for activity and is situated at the active site of the enzyme.

PMID- 16815544
TI  - Effects of pH and ionic strength on the assembly and bundling of FtsZ
      protofilaments: a possible role of electrostatic interactions in the bundling of
      protofilaments.
AB  - Assembly, bundling and stability of FtsZ protofilaments are important for the
      formation and functioning of the cytokinetic Z-ring during bacterial division. We
      found that the bundling of FtsZ protofilaments decreased strongly with increasing
      pH from 6.0 to 7.9, while the assembly of FtsZ monomers did not decrease
      considerably. In addition, the disassembly of FtsZ protofilaments was strongly
      suppressed at pH 6.0 as compared to the elevated pHs. The far-UV circular
      dichroism spectra of the native FtsZ and the tryptophan emission spectra of
      mutated FtsZ (Y371W) did not change by increasing pH from 6 to 7.9 indicating
      that the structure of FtsZ was not altered significantly. Further, the inhibition
      of bundling of FtsZ protofilaments predominantly, and the inhibition of assembly
      to a lesser extent by salt indicated that electrostatic interactions are
      important for the assembly and bundling of FtsZ protofilaments. These
      observations are supported by the results of computational docking of Escherichia
      coli dimer structure. The results suggest that the basic intracellular pH (7.4
      7.8) of E. coli may play a role in regulating the assembly dynamics of FtsZ in
      the Z-ring by reducing protofilament stability and bundling in bacterial
      cytoplasm.

PMID- 16815545
TI  - A constitutive model for protein-based materials.
AB  - Protein-based materials are critical to the construction of tissue substitutes
      that exhibit precisely defined mechanical properties. Under physiologically
      relevant conditions, materials derived from natural or synthetic structural
      proteins are characterized by nonlinear elastic responses at medium and large
      deformations, time-dependent or viscoelastic behavior, and display the effects of
      strain-induced structural changes. Although a constitutive model that accurately
      describes mechanical behavior is essential for the rational design of tissue
      constructs, few models account for all of these characteristics. In this report,
      we present a new constitutive model for protein based materials, in which
      nonlinear elasticity is captured by the Arruda-Boyce eight-chain model, time
      dependant viscoelasticity is described by a generalized Maxwell model, and the
      effect of strain-induced structural change is incorporated using a network
      alteration theory originally proposed by Tobolsky. The model was applied to a
      number of protein-based materials and cell containing constructs, including
      recombinant elastin-mimetic protein polymers and fibroblast populated collagen
      gel matrices. Significantly, numerical implementation of this model is
      straightforward and mechanical behavior accurately described under a variety of
      loading conditions. Moreover, when calibrated using stress relaxation data alone,
      the model accurately predicted cyclic loading responses. Although limitations
      exist, this model provides a convenient tool to correlate viscoelastic data
      obtained by different testing modes and may assist in reducing the number of
      experimental tests required to fully capture the range of viscoelastic responses
      of protein-based materials.

PMID- 16815546
TI  - Low-dose thalidomide in combination with oral fludarabine and cyclophosphamide is
      ineffective in heavily pre-treated patients with chronic lymphocytic leukemia.
AB  - Elevated levels of TNF-alpha have been associated with progressive disease in
      patients with chronic lymphocytic leukemia (CLL). Thalidomide has been shown to
      inhibit production of TNF-alpha. We investigated the effects of thalidomide on
      clinical outcome and TNF-alpha serum levels in five pre-treated CLL patients. The
      schedule consisted on daily thalidomide (Thal), oral fludarabine (Flu) and oral
      cyclophosphamide (CTX). Median duration of treatment was 60 days; four patients
      stopped treatment for disease progression and one patient for neurological
      toxicity. Serum TNF-alpha levels did not show any decrease during treatment. Low
      dose thalidomide is not effective in CLL patients with refractory disease.

PMID- 16815547
TI  - Relationship between dose of emamectin benzoate and molting response of ovigerous
      American lobsters (Homarus americanus).
AB  - A widely-prescribed treatment to control sea lice on cultured salmon is the
      administration of feed medicated with SLICE (active ingredient emamectin benzoate
      (EMB)). High doses of EMB can disrupt the molt cycle of ovigerous American
      lobsters, causing them to enter proecdysis prematurely and lose their attached
      eggs when the shell is cast. To determine the dose response to EMB, lobsters were
      forced to ingest doses that ranged from 0.05 to 0.39 microg g(-1). A significant
      proportion of lobsters given doses of 0.39 and 0.22 microg g(-1) (37% and 23%,
      respectively) molted prematurely, almost a year earlier than the control group.
      All the lobsters in the 0.05 and 0.12 microg g(-1) groups molted at the normal
      time and the mean time of molt was similar to that of the control group. Thus,
      the no-observed-effect level (NOEL) and lowest-observed-effect level (LOEL) of
      EMB on the molt cycle were 0.12 and 0.22 microg EMB g(-1) lobster, respectively.
      To acquire the LOEL, a 500-g lobster would have to consume 22 g of salmon feed
      medicated with SLICE at a level of 5 microg EMB g(-1) feed.

PMID- 16815548
TI  - Chemical and toxicological characterisation of PBDFs from photolytic
      decomposition of decaBDE in toluene.
AB  - A substantial formation of PBDF congeners was observed during photolytic
      decomposition of decaBDE in toluene. The decaBDE degradation was monitored by
      chemical and toxicological analysis and in all, twenty-seven mono- to
      hexasubstituted polybrominated dibenzofurans (PBDFs) were detected in toluene
      solutions of decabromodiphenyl ether (decaBDE) after irradiation with UV-A, UV-AB
      and UV-ABC. The concentration levels of PBDFs formed after 16 h of UV exposure
      increased with wider spectra and were determined to be 3.5, 4.2 and 14 microg/ml
      after UV-A, UV-AB and UV-ABC irradiation, respectively. In accordance, bioassay
      derived TEQs (bio-TEQs), determined with the DR-CALUX assay, increased with a
      similar pattern. The PBDFs formed after the three UV exposures accounted for
      0.31%, 0.35% and 1.2% of the initial amount of decaBDE (molar basis). The PBDF
      congener patterns were consistent in all three UV experiments which imply that no
      alterations were induced in the PBDF formation or degradation processes due to
      differences in UV irradiation. However, these processes tended to increase with
      wider spectra and increasing radiation energy most likely due to the strong
      absorbance of for example decaBDE at shorter wavelengths. After total decaBDE
      decomposition the PBDF formation increased significantly in the UV-ABC
      experiment. The tetra to hexasubstituted BDFs constituted the majority of
      detected compounds in all experiments. In all samples, the estimated chemical TEQ
      indicate that the bio-TEQs observed are largely explained by the presence of non
      2,3,7,8-substituted PBDFs with relatively low toxicological potencies.

PMID- 16815549
TI  - Germanium dioxide induces mitochondria-mediated apoptosis in Neuro-2A cells.
AB  - Germanium (Ge) is commonly used in the semiconductor industry as well as health
      promoting and medical field. Biologically, germanium possesses erythropoietic,
      anti-microbial, anti-tumor, anti-amyloidosis, and immunomodulative effects.
      However, toxic effects of Ge-containing compounds on kidney, muscle, neuronal
      cells, and nerves have been reported. Mitochondrial dysfunction was found to be
      involved in the pathogenesis of GeO(2)-induced nephropathy and myopathy. Since it
      is well known that mitochondria play a major role in apoptosis triggered by many
      stimuli, an effort was made to examine whether the Ge-induced neurotoxicity
      occurs through mitochondria-mediated apoptosis. A mouse neuroblastoma cell line,
      Neuro-2A, was used in the present study. After incubating with 0.1-800microM of
      GeO(2) for 0-72h, the cell viability of Neuro-2A cells was inhibited in a dose-
      and time-dependent manner. Further analysis showed that aside from the changes in
      the nuclear morphology responsible for apoptosis, the release of cytochrome c,
      the loss of mitochondrial membrane potential, the translocation of Bax, and the
      reduction of Bcl-2 expression were also observed in Neuro-2A cells after GeO(2)
      treatment. These results indicate that the mitochondria-mediated apoptosis is
      involved in this in vitro model of GeO(2)-induced neurotoxicity.

PMID- 16815550
TI  - 1-BP inhibits NF-kappaB activity and Bcl-xL expression in astrocytes in vitro and
      reduces Bcl-xL expression in the brains of rats in vivo.
AB  - 1-Bromopropane (1-BP) has been widely used as a substitute for chlorofluorocarbon
      that destroys the ozone layer. Although the central neurotoxicity of 1-BP has
      been recently reported, a molecular mechanism is not clear. In particular, the
      effects on cells in brain have not been fully analyzed. Here, we studied the
      effects of 1-BP on the activation of transcription factors involved in anti
      apoptotic function or cell survival in astrocytes. Astrocytoma cell lines, U251,
      U373 and VM, or murine primary astrocytes were used for in vitro assay. DNA
      binding activities of NF-kappaB in these cells induced by interleukin (IL)-1 or
      LPS were inhibited by 1-BP. Consequently, the treatment of U251 cells with 1-BP
      resulted in suppression of NF-kappaB reporter activity. Furthermore, 1-BP blocked
      IkappaBalpha degradation, which is important for NF-kappaB activation. In
      addition, the level of Bcl-xL mRNA, which is known as an anti-apoptotic gene,
      were reduced in U251 treated with 1-BP or in the brain from rat exposed to 1-BP
      (400 ppm, 12 weeks). These results suggest that subchronic inhalation exposure to
      1-BP vapor may affect the Bcl-xL expression in astrocytes.

PMID- 16815551
TI  - Paraquat exposure as an etiological factor of Parkinson's disease.
AB  - Parkinson's disease (PD) is a multifactorial chronic progressive
      neurodegenerative disease influenced by age, and by genetic and environmental
      factors. The role of genetic predisposition in PD has been increasingly
      acknowledged and a number of relevant genes have been identified (e.g., genes
      encoding alpha-synuclein, parkin, and dardarin), while the search for
      environmental factors that influence the pathogenesis of PD has only recently
      begun to escalate. In recent years, the investigation on paraquat (PQ) toxicity
      has suggested that this herbicide might be an environmental factor contributing
      to this neurodegenerative disorder. Although the biochemical mechanism through
      which PQ causes neurodegeneration in PD is not yet fully understood, PQ-induced
      lipid peroxidation and consequent cell death of dopaminergic neurons can be
      responsible for the onset of the Parkinsonian syndrome, thus indicating that this
      herbicide may induce PD or influence its natural course. PQ has also been
      recently considered as an eligible candidate for inducing the Parkinsonian
      syndrome in laboratory animals, and can therefore constitute an alternative tool
      in suitable animal models for the study of PD. In the present review, the recent
      evidences linking PQ exposure with PD development are discussed, with the aim of
      encouraging new perspectives and further investigation on the involvement of
      environmental agents in PD.

PMID- 16815552
TI  - Citrobacter infections in a tertiary care hospital in Northern India.
AB  - OBJECTIVES: This prospective study was carried out to look for the frequency of
      isolation of Citrobacter species from clinical specimens and study their
      antimicrobial susceptibility pattern. METHODS: Patients from whom Citrobacter
      species were isolated during routine diagnostic testing from January to December
      2004 were included in the study. Isolates were identified by standard biochemical
      tests. Antimicrobial susceptibility testing was performed by disk diffusion
      method as per National Committee of Clinical Laboratory Standards (NCCLS)
      guidelines. RESULTS: Citrobacter species were isolated from a total of 205
      patients. Infection was nosocomially acquired in 94.6% patients. One hundred
      eighty one (88.3%) patients had significant underlying illnesses. Culture yielded
      Citrobacter koseri in 185 (90.2%) and Citrobacter freundii in 20 (9.8%) patients.
      The distribution of isolates was as follows: urine (46.2%), respiratory tract
      (16.3%), blood (15.8%), pus (12.1%) and sterile body fluids (9.3%). Drug
      resistance was observed to be more in C. koseri as compared to C. freundii.
      CONCLUSIONS: Citrobacter infections are often nosocomially acquired, seen in
      patients with significant underlying diseases and isolates are commonly drug
      resistant. Adoption of hospital infection control practices and a good antibiotic
      policy may prevent their spread.

PMID- 16815553
TI  - Haptoglobin 1-1 genotype and the risk of life-threatening Streptococcus
      infection: evolutionary implications.

PMID- 16815554
TI  - Current state, achievements, and future prospects of polymeric micelles as
      nanocarriers for drug and gene delivery.
AB  - Polymeric micelles, self-assemblies of block copolymers, are promising
      nanocarrier systems for drug and gene delivery. Until now, several micellar
      formulations of antitumor drugs have been intensively studied in preclinical and
      clinical trials, and their utility has been demonstrated. Even compared with long
      circulating liposomes, polymeric micelles might have several advantages, such as
      controlled drug release, tissue-penetrating ability and reduced toxicity such as
      hand-foot syndrome and hypersensitivity reaction. Importantly, critical features
      of the polymeric micelles as drug carriers, including particle size, stability,
      and loading capacity and release kinetics of drugs, can be modulated by the
      structures and physicochemical properties of the constituent block copolymers.
      Also, nano-engineering of block copolymers might allow the preparation of
      polymeric micelles with integrated smart functions, such as specific-tissue
      targetability, as well as chemical or physical stimuli-sensitivity. Thus,
      polymeric micelles are nanotechnology-based carrier systems that might exert the
      activity of potent bioactive compounds in a site-directed manner, ensuring their
      effectiveness and safety in the clinical use.

PMID- 16815555
TI  - Lower urinary tract symptoms and depressive symptoms in elderly men.
AB  - BACKGROUND: To evaluate the impact of moderate to severe lower urinary tract
      symptoms (LUTS) on clinically significant depressive symptoms in elderly Chinese
      men aged 65 and above. METHODS: In a large prospective cohort of 2000 Chinese men
      aged 65 to 92 years of age in Hong Kong, the association between moderate to
      severe lower urinary tract symptoms and clinically relevant depressive symptoms
      was studied. After excluding men with prostate or bladder cancer or surgery, 1980
      subjects provided response to a structured interviewer-administered questionnaire
      and physical examination. A case-control analysis was performed, comparing
      subjects with clinically relevant depressive symptoms (cases) to those without
      depressive symptoms (controls). RESULTS: In multiple analyses adjusting for all
      factors that were shown to be significantly associated with having clinically
      relevant depressive symptoms in the initial bivariate analyses, being widowed,
      divorced or single were associated with increased risk of having clinically
      relevant depressive symptoms. Having a history of cardiac disease, being a
      current smoker and the use of corticosteroid were also associated with increased
      risk. Having moderate to severe LUTS was significantly associated with increased
      odds of having clinically relevant depressive symptoms (OR: 2.40; CI: 1.68-3.43)
      even after adjustment. LIMITATION: This study was cross-sectional and there were
      no clinician-based diagnostic interviews that were conducted to diagnose clinical
      depression and thus only clinically relevant depressive symptoms were assessed.
      CONCLUSIONS: In elderly men, moderate to severe LUTS are important public health
      problems that are associated with increased risk of having clinically relevant
      depressive symptoms. These findings suggest that physicians who deal with
      patients with moderate to severe LUTS should consider the psychological health of
      their patients as this population is at risk of having clinically relevant
      depressive symptoms.

PMID- 16815556
TI  - Dietary folate and vitamins B12, B6, and B2 intake and the risk of postpartum
      depression in Japan: the Osaka Maternal and Child Health Study.
AB  - BACKGROUND: Previous studies showed an inverse association between folate intake
      and depression. However, epidemiological evidence for folate intake and
      postpartum depression is unavailable. This prospective study examined the
      relationship of dietary consumption of folate and B vitamins during pregnancy
      with the risk of postpartum depression. METHODS: Study subjects were 865 Japanese
      women. Dietary data were obtained during pregnancy from a validated self
      administered diet history questionnaire. Postpartum depression was defined as
      present when subjects had an Edinburgh Postnatal Depression Scale score of 9 or
      higher between 2 and 9 months postpartum. Adjustment was made for age, gestation,
      parity, cigarette smoking, alcohol intake, family structure, family income,
      education, changes in diet in the previous 1 month, season when data at baseline
      were collected, body mass index, time of delivery before the second survey,
      medical problems in pregnancy, baby's sex, and baby's birth weight. RESULTS:
      Postpartum depression developed in 121 subjects (14.0%) 2 to 9 months postpartum.
      There was no measurable association between intake of folate, cobalamin, or
      pyridoxine and the risk of postpartum depression. Compared with riboflavin intake
      in the first quartile, only riboflavin consumption in the third quartile was
      independently related to a decreased risk of postpartum depression (multivariate
      odds ratio: 0.53, 95% CI: 0.29-0.95, P for trend=0.55). LIMITATIONS: Personal and
      family psychiatric history, sociocultural factors, and personal and family
      relations were not controlled for. The possibility of misclassification of
      dietary information during pregnancy should be considered. CONCLUSIONS: Our
      results suggest that moderate consumption of riboflavin may be protective against
      postpartum depression.

PMID- 16815557
TI  - Distinguishing bipolar and unipolar disorders: an isomer model.
AB  - BACKGROUND: As division between unipolar and bipolar disorders can be
      problematic, we sought to develop a self-report questionnaire of mood 'highs'
      that would both distinguish true Bipolar Disorder from any elevated mood states
      in unipolar depression and sharpen the distinction between Bipolar I and II
      conditions. METHOD: A 46-item questionnaire was developed and completed by 157
      out-patients presenting with a major depressive episode, and clinically diagnosed
      as having either Bipolar I (BP-I), Bipolar II (BP-II) or Unipolar (UP)
      depression, although DSM-IV duration criteria for BP-I and BP-II were not
      imposed. RESULTS: Factor analyses identified four key constructs to mood 'highs',
      while additional analyses refined the questionnaire to 27 items. The refined
      measure was highly accurate in distinguishing composite Bipolar (BP-I and BP-II)
      from UP subjects (AUC = 0.93, sensitivity = 81%; specificity = 98%, positive
      predictive value = 0.95). Questionnaire scores were similar for BP-I and BP-II
      subjects, raising the possibility that the core mood state differs little in
      severity across the two expressions, and that their distinction allows an
      alternative model that weights the presence or absence of psychotic features.
      CONCLUSIONS: Our study advances understanding of boundary distinctions between
      bipolar and unipolar mood disorders, and between BP-I and BP-II conditions, and
      allows consideration of a model distinguishing BP-I from BP-II by the presence of
      psychotic features only. The described model is the mirror image of a
      hierarchical structural model for conceptualizing psychotic and melancholic
      depression, allowing an 'isomer model' for linking the mood swing states.

PMID- 16815559
TI  - Is mPGES-1 a promising target for pain therapy?
AB  - Cyclooxygenase (COX) inhibitors are widely used analgesic and anti-inflammatory
      drugs. Owing to undesirable effects caused by unselective COX inhibitors and
      selective COX-2 inhibitors, microsomal prostaglandin E(2) synthase-1 has been
      considered as an alternative target for the development of analgesic drugs.
      However, recent findings question the usefulness of this terminal synthase as a
      promising drug target for pain therapy.

PMID- 16815558
TI  - TPMT, UGT1A1 and DPYD: genotyping to ensure safer cancer therapy?
AB  - The Food and Drug Administration (FDA) has approved label changes for two
      anticancer drugs, 6-mercaptopurine (6-MP) and irinotecan, to include
      pharmacogenetic testing as a potential means to reduce the rate of severe toxic
      events. Comprehensive evaluation of the clinical benefit and cost effectiveness
      of screening strategies with these tests has not been completed. However, the FDA
      decided that evidence indicates sufficient benefit to warrant informing
      prescribers, pharmacists and patients of the availability of pharmacogenetic
      tests and their possible role in the selection and dosing of these anticancer
      agents. Reviewing the gene-drug-phenotype relationships of 6-MP, irinotecan and 5
      fluorouracil reveals properties of these relationships that lead to a clinically
      useful pharmacogenetic test. Research in the near future should clarify the role
      of pharmacogenetic testing in reducing the risk of severe toxicity and determine
      how these same tests might identify a subset of patients who should safely
      receive higher doses of treatment to derive the same benefit as the rest of the
      patient population.

PMID- 16815560
TI  - Serotype-specific detection of adeno-associated virus during laboratory
      preparation.
AB  - Adeno-associated virus (AAV) is a small single-stranded DNA member of the family
      Parvoviradae with at least eight recognized human serotypes, several of which are
      being studied as candidate vectors for gene therapy. When multiple serotypes are
      handled in the same laboratory, it is critical to know the serotype of a sample
      with certainty. Here, a rapid and reliable PCR-based method is presented for the
      identification of serotypes 2, 3B or 6 and for screening for cross contamination.
      The PCR assay is based on the use of differentially annealing, serotype-specific
      primer pairs targeted to the hypervariable regions of the capsid coding region of
      the AAV genome. Identity is determined by the presence of a PCR product of size
      specific to each serotype. Multiplexing the reaction allows all serotypes to be
      queried in a single reaction tube and greatly diminishes the presence of false
      positives. The method is capable of detecting as little as 25 fg of a
      contaminating serotype and is potentially extensible to other AAV serotypes.

PMID- 16815562
TI  - Nature and nurture in language acquisition: anatomical and functional brain
      imaging studies in infants.
AB  - Speech processing in adults relies on precise and specialized networks, located
      primarily in the left hemisphere. Behavioral studies in infants indicate that a
      considerable amount of language learning already takes place in the first year of
      life in the domains of phonology, prosody and word segmentation. Thanks to
      neuroimaging, we can move beyond behavioral methods and examine how the infant
      brain processes verbal stimuli before learning. These studies reveal a structural
      and functional organization close to what is described in adults and suggest a
      strong bias for speech processing in these regions that might guide infants as
      they discover the properties of their native language, although no evidence can
      be provided as yet for speech specificity of such networks. This review is part
      of the INMED/TINS special issue "Nature and nurture in brain development and
      neurological disorders", based on presentations at the annual INMED/TINS
      symposium (http://inmednet.com/).

PMID- 16815561
TI  - A simplified method for cloning of short interfering RNAs from Brassica juncea
      infected with Turnip mosaic potyvirus and Turnip crinkle carmovirus.
AB  - RNA silencing is a plant defense mechanism in which virus infected plants produce
      short interfering RNAs (siRNAs) derived from viral RNA, that attack the virus at
      the post-transcriptional level. In a previous study on Cymbidium ringspot
      tombusvirus (CymRSV) infection in Nicotiana benthamiana, siRNAs (determined by
      cloning and sequencing) predominantly originated from the sense (+) strand of the
      viral RNA, suggesting that the majority of siRNAs are produced through the direct
      cleavage of the virus single strand (ss) RNA by the plant Dicer-like enzyme. To
      test whether this asymmetry in strand polarity is a generic rule for all plant
      viruses, siRNAs from Brassica juncea, either singly infected by Turnip mosaic
      potyvirus (TuMV, the family Potyviridae), or doubly infected with TuMV and Turnip
      crinkle carmovirus (TCV, the family Tombusviridae) were investigated. A
      simplified siRNA cloning method was developed, using a single ligation reaction
      to attach both 5' and 3' adapters to the target short RNAs followed by one-step
      RT-PCR amplification. In the TCV infection, as for the CymRSV infection, siRNAs
      were produced predominantly (97.6%) from the +ss RNA. However, for TuMV
      infections, siRNAs were derived from both strands (+/-, 58.1-41.9%), indicating
      the presence of alternative siRNA production mechanisms.

PMID- 16815563
TI  - Antivirals for influenza: historical perspectives and lessons learned.
AB  - The development of the currently available classes of antivirals, the M2 proton
      channel inhibitors and the neuraminidase inhibitors, provides valuable
      perspectives relevant to the field of antiviral chemotherapy in general and
      insights into aspects of viral pathogenesis and antiviral resistance relevant
      specifically to influenza. The efficacy observed with these antiviral drugs has
      proven the importance of these antiviral targets, as well as the principle that
      chemoprophylaxis and early treatment are possible in influenza infections with
      small molecular weight inhibitors.

PMID- 16815564
TI  - Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition,
      consolidation and retrieval in Morris water maze task.
AB  - Orexin containing neurons in the lateral hypothalamic area (LHA) produce orexin-A
      (hypocretin-1) and orexin-B (hypocretin-2) and send their axons to the
      hippocampus, which predominantly expresses orexin 1 receptors (OX1Rs) showing a
      higher affinity to orexin-A. Recent studies have shown that central
      administration of orexin-A has an effect on learning and memory but literature
      concerning the role of orexinergic system in cognition remains controversial.
      Therefore, we examined the effect of pre-training, post-training and pre-probe
      trial intrahippocampal CA1 administration of a selective OX1R the orexin 1
      receptor antagonist SB-334867-A (1.5, 3, 6 microg/0.5 microl) on acquisition,
      consolidation and retrieval in a single-day testing version of Morris water maze
      (MWM) task. Our results show that, SB-334867-A impaired acquisition,
      consolidation and retrieval of MWM task as compared with the control group. This
      drug had no effect on escape latency of a non-spatial visual discrimination task.
      Therefore, it seems that endogenous orexins, especially orexin-A, play an
      important role in spatial learning and memory in the rat.

PMID- 16815565
TI  - Molecular cloning and characterization of the protein kinase A regulatory subunit
      of Trypanosoma cruzi.

PMID- 16815566
TI  - Plasma adrenomedullin and endothelin-1 concentration during low-dose dobutamine
      infusion: Relationship between pulmonary uptake and pulmonary vascular
      pressure/flow characteristics.
AB  - AIM: To study the role of endothelin (ET-1) and adrenomedullin (AM) on pulmonary
      vascular pressure/flow characteristic (pulmonary arterial pressure/cardiac output
      (Pap/CO)) during low-dose dobutamine infusion. METHODS: Case control study of 14
      patients (12 men, 2 women) with severe lung disease (chronic obstructive
      pulmonary disease, COPD n=5; cystic fibrosis, CF n=9) and 5 control subjects
      (CTRL, 4 men, 1 woman). ET-1 and AM plasma levels in pulmonary artery (mixed
      venous blood, ven) and aorta or femoral artery (arterial, art), were measured at
      baseline and during dobutamine infusion (5-10-15 mcg kg(-1) min(-1)). The Ppa/CO
      coordinates obtained at baseline and during dobutamina infusion for each patients
      were used to calculate the Slope and Intercept by linear regression analysis.
      RESULTS: Baseline hemodynamics measurements were similar in the three groups with
      a trend towards a mild elevation in Ppa in CF group (Ppa mm Hg: CTRL 19+/-3.5,
      COPD 19.4+/-5.5, CF 22.7+/-7.5). Baseline plasma ET-1(ET-1ven pg ml(-1): CTRL
      13.9+/-6.7, COPD 20.1+/-14, CF 20.4+/-7.1; ET-1art pg ml(-1): CTRL 16.7+/-6.4,
      COPD 20.1+/-11.7, CF 18.1+/-3.9) and AM (AMven pg ml(-1): CTRL 15.8+/-5, COPD
      31.8+/-17.6, CF 27.7+/-7.6; AMart pg ml(-1): CTRL 15.9+/-1.4, COPD 21.4+/-3.8, CF
      27+/-7.6) showed a trend towards higher value among patients' groups compared to
      the controls. Baseline ET-1 pulmonary gradient did not show significant
      difference among the three groups as well AM pulmonary gradient. Dobutamine
      infusion caused a comparable increase of heart rate and CO in the three groups.
      Mean pulmonary pressure had a trend towards a greater increase in COPD and CF
      than in controls, consequently, pulmonary Pap/CO relationship showed a steeper
      slope in patients' groups (Slope mm Hg L(-1) min(-1): CTRL 0.9+/-0.3, COPD 2.1+/
      0.8 p<0.02 vs. CTRL, CF 1.9+/-0.9 p<0.03 vs CTRL). During dobutamine plasma ET-1
      and AM showed a great individual variability resulting in no significant
      difference among groups. ET-1 pulmonary gradient showed a trend towards pulmonary
      uptake in patients' groups (ET-1art-ven pg min(-1): CTRL 2.7+/-2.9, COPD-6.1+/
      7.8, CF -4+/-4.8) while AM pulmonary gradient did not show any particular
      pattern. During dobutamine ET-1 was significantly correlated to Pap/CO
      characteristics (Slope and ET-1ven, r=-0.59, p<0.05; Slope and ET-1art-ven, r=
      0.60, p<0.05; Intercept and ET-1art-ven, r=0.63, p<0.004), and ET-1art-ven was
      the only independent variable related to Slope and Intercept. CONCLUSIONS: In
      patients with moderate pulmonary vascular impairment, ET-1 pulmonary gradient,
      but not AM pulmonary gradient, is inversely correlated with pulmonary incremental
      resistance, suggesting a role of ET-1 in the regulation of pulmonary vascular
      resistance.

PMID- 16815567
TI  - Characterization of the MCT-1 pseudogene: identification and implication of its
      location in a highly amplified region of chromosome 20.
AB  - The MCT-1 oncogene was initially identified as an amplified gene on chromosome
      Xq22-24 in a T-cell lymphoma. MCT-1 is over-expressed in a subset of diffuse
      large B-cell lymphoma (DLBCL), a common form of Non-Hodgkin's Lymphoma (NHL). We
      have identified a pseudogene for MCT-1 (PsiMCT-1) that is located on chromosome
      20q11.2, a region within an amplicon containing several important genes
      frequently amplified in certain breast and ovarian cancers. Genomic analysis
      revealed that PsiMCT-1 is a processed pseudogene. Interestingly, both MCT-1 and
      its pseudogene are located on regions of the genome that are frequently amplified
      in several different human malignancies. MCT-1 is the oldest known oncogene and
      its insertion as a pseudogene occurred at a later time point in evolution.
      Existence of PsiMCT-1 should be considered when analyzing genomic amplification
      and or expression of MCT-1. Analysis of MCT-1 and PsiMCT-1 might provide clues to
      cancer genes and their evolution across species.

PMID- 16815568
TI  - Congenital complete heart block and maternal connective tissue disease.
AB  - Congenital complete heart block can be isolated or can occur in association with
      other structural heart diseases. Isolated congenital complete heart block (CCHB)
      is due to transplacental transfer of autoantibodies from mothers with connective
      tissue disease. Congenital heart block is usually complete, but incomplete
      blocks, sinus bradycardia and QTc prolongation are also reported. Anti SS A and
      Anti SS B antibodies transferred from mothers have inflammatory and
      arrhythmogenic effects in the fetal conduction system. Cardiac manifestations
      reported include dilated cardiomyopathy, endocardial fibroelastosis and mitral
      insufficiency. Low ventricular rate, QT prolongation and arrhythmias on
      monitoring are high risk features. CCHB has a mortality of 30%, and 60% of
      infants require pacemaker therapy. Fetal echocardiography is useful in early
      diagnosis. Prophylactic steroid therapy is controversial. Beta adrenergic
      agonists were tried in mothers with fetuses having congenital heart block to
      increase fetal heart rate. Early pacemaker therapy is indicated in patients with
      symptomatic bradycardia and ventricular dysfunction. The indications for pacing
      in congenital heart block continue to evolve with advances in techniques and most
      of these children will ultimately require permanent pacemakers by adulthood.

PMID- 16815569
TI  - Pulmonary embolism in the Chinese population.

PMID- 16815570
TI  - The aortic distensibility alteration is an index of influence of ischemic
      preconditioning to myocardial performance.
AB  - BACKGROUND: Ischemic preconditioning (IP) is a cardioprotective phenomenon,
      induced by brief episodes of myocardial ischemia, which is supposed to affect not
      only the myocardium, but also the entire cardiovascular system. Considering that
      patients with coronary artery disease (CAD) have also been described to present
      impaired aortic mechanical properties, we tried to investigate the possible
      influence of the late phase of IP on aortic distensibility in patients with CAD.
      METHODS: Fifty patients, aged 48 to 72 (mean, 57+/-6 years), with
      angiographically confirmed CAD and exercise-induced myocardial ischemia,
      underwent two treadmill exercise testings (ETs). The second ETs was performed the
      next day. Thallium-201 scintigraphy was performed during the first and the second
      ET. Aortic distensibility was evaluated before each exercise testing by a non
      invasive technique, using two-dimensional guided M-mode transthoracic
      echocardiography and arterial pressure was measured simultaneously at the
      brachial artery by sphygmomanometry. RESULTS: The patients were divided in 2
      groups according to the extent of myocardial ischemia at peak exercise of the
      second test, compared to the first test. In 35 (70%) of the studied patients
      ischemia signs were reduced during the second ET (Group A), while in the rest 15
      (30%) of the patients (Group B) no improvement or even worsening of the observed
      ischemia signs was demonstrated by the studied exercise parameters and the extent
      of myocardial ischemia in thallium-scintigraphy. Increased aortic distensibility
      during the second measurement was found in 33 (94%) of the 35 patients of Group A
      but only in 1 (7%) of the 15 patients of Group B. Aortic distensibility was found
      to be significantly improved in patients of Group A, while it was found to be
      worsened in Group B patients. CONCLUSIONS: The aortic distensibility alteration
      could be used as an index of influence of ischemic preconditioning to exercise
      induced myocardial ischemia, which could be considered indicative of the systemic
      effects of IP in humans.

PMID- 16815571
TI  - Effects of short-term exercise training on symptoms and quality of life in
      patients with chronic atrial fibrillation.
AB  - BACKGROUND: A randomised study was conducted to determine if short-term exercise
      training in patients with chronic atrial fibrillation (AF) might improve symptoms
      and health-related quality of life (HRQoL). METHODS: AF patients (64+/-7 years)
      were randomised to exercise training (n=15) or a 2-month control period (n=15)
      followed by an exercise training program (ETP). The ETP consisted of 24 training
      sessions with aerobic exercise and muscle strengthening. A cycle ergometer test,
      with recording of perceived exertion on the Borg scale, was performed. The
      participants completed HRQoL questionnaires, the Short-Form 36 (SF-36) and
      Symptom and Severity Checklist (SSCL), before and after training. Because there
      were no changes after two months in the control group, pooled data for all
      patients are presented before and after training. RESULTS: Four of the eight SF
      36 scales improved significantly (p<0.05) following training: physical
      functioning (82+/-14 pre-ETP, 86+/-10 post-ETP), bodily pain (82+/-17 pre-ETP,
      92+/-14 post-ETP), vitality (61+/-14 pre-ETP, 68+/-13 post-ETP) and role
      emotional (85+/-28 pre-ETP, 94+/-20 post-ETP). The SF-36 physical component
      summary scale also increased from 49+/-6 pre-ETP to 52+/-6 post-ETP (p<0.05).
      Significant improvements were also observed for summary and specific symptom
      scores of the SSCL. Exercise capacity improved by 41+/-20% and perceived exertion
      during testing by 1.4 points after training (p<0.05 for both). CONCLUSIONS: The
      study demonstrates a significant improvement in HRQoL, symptoms during exercise
      testing and exercise capacity after a short-term exercise training program in
      patients with chronic AF.

PMID- 16815572
TI  - Right bundle-branch block in anterior acute myocardial infarction in the coronary
      intervention era: acute angiographic findings and prognosis.
AB  - BACKGROUND: Previous studies in the prethrombolytic or thrombolytic era have
      reported that right bundle-branch block (RBBB) is associated with poor clinical
      outcome in patients with acute myocardial infarction (AMI). METHODS AND RESULTS:
      The purpose of this study was to examine the relations between RBBB and
      angiographic findings or clinical outcomes in patients with AMI in the coronary
      intervention era. A total of 430 patients with a first anterior AMI who underwent
      coronary angiography within 12 h after the onset were enrolled in this study.
      Seventy-one patients (17%) had RBBB documented during their hospital stay. RBBB
      was documented on admission in 35 patients. Patients with RBBB were older
      (p<0.01) and had prodromal angina less frequently (p=0.03) than those without. On
      the initial angiograms, patients with RBBB had an occluded left anterior
      descending artery (p<0.01) and multivessel disease (p=0.01) more frequently than
      those without. Thirty-day mortality rate was significantly higher in patients
      with RBBB than in those without (14.0% vs 1.9%, p<0.01). Multiple logistic
      regression analysis demonstrated that RBBB (odds ratio 5.89, p<0.01) and
      multivessel disease (odds ratio 4.36, p=0.01) were independent predictors of 30
      day mortality. CONCLUSIONS: Our data suggested that RBBB was still associated
      with poor clinical outcome in patients with anterior AMI even in the coronary
      intervention era.

PMID- 16815573
TI  - Poor recognition of symptoms and access to medical care in women with myocardial
      infarction.

PMID- 16815574
TI  - Rapid PCR-based method for detection and differentiation of Didymiaceae and
      Physaraceae (myxomycetes) in environmental samples.
AB  - Ecological studies of myxomycetes have been limited by the absence of universal
      cultivation techniques and the lack of life stage independent identification
      methods. We designed a novel PCR primer pair for the specific amplification of
      small subunit ribosomal RNA gene of Didymiaceae and Physaraceae. The primers
      produced amplicons from 192 fruiting body samples belonging to 10 genera. Twenty
      four samples yielded longer fragments and sequence analysis revealed the presence
      of intron(s). As for the exonic regions, while sequence heterogeneities within a
      single species/varietas/forma were frequently observed, identical sequences were
      obtained only from identical species/varietas. The effectiveness of this primer
      pair in the analysis of morphologically unidentifiable samples was confirmed with
      the applications to samples of environmental plasmodium/sclerotium and soil.
      Denaturing gradient gel electrophoresis analysis was also tested with the soil
      samples. The results presented here demonstrate this PCR-based method can
      facilitate further ecological studies of Physaraceae and Didymiaceae in the
      environment.

PMID- 16815575
TI  - Spatially-correlated mass spectrometric analysis of microbe--mineral
      interactions.
AB  - A new methodology for examining the interactions of microbes with heterogeneous
      minerals is presented. Imaging laser desorption Fourier transform mass
      spectrometry was used to examine the colonization patterns of Burkholderia
      vietnamiensis G4 (previously Burkholderia cepacia G4) on a heterogeneous basalt
      sample. Depth-profile imaging found that the bacterium preferentially colonized
      the plagioclase mineral phase within the basalt.

PMID- 16815576
TI  - DNA mimicry by proteins and the control of enzymatic activity on DNA.
AB  - Cells are unable to perform any function on their DNA in the absence of proteins,
      and it is of vital importance that these proteins only perform their function at
      appropriate times during the cell cycle. Thus, DNA-binding proteins are always
      controlled by a wide range of other factors, primarily other proteins. These
      controlling factors usually block access of the protein to the DNA, often
      operating by simple competitive inhibition. However, it has recently been
      demonstrated that DNA-binding proteins can be controlled by the direct binding of
      the control protein to the DNA-binding site on the first protein. The structures
      of these control proteins have revealed that they mimic the structure and
      electrostatics of DNA. This review highlights the roles of DNA mimics in the
      control of DNA-binding proteins, suggests other possible candidate proteins using
      DNA mimicry, and puts forward a range of potential uses of DNA mimics.

PMID- 16815577
TI  - Blood substitutes based on nanobiotechnology.
AB  - Stimulated by concerns of potential infective agents in donated blood, commercial
      enterprises have attempted to develop blood substitutes since the 1900s. After
      several years of development, a few of the many leads are showing promise. In
      this article, nanobiotechnological approaches that are now in phase III clinical
      trials are reviewed, followed by a discussion of how important basic knowledge
      gained is being used to develop new generations of blood substitutes based on
      nanobiotechnology.

PMID- 16815578
TI  - Horseradish and soybean peroxidases: comparable tools for alternative niches?
AB  - Horseradish and soybean peroxidases (HRP and SBP, respectively) are useful
      biotechnological tools. HRP is often termed the classical plant heme peroxidase
      and although it has been studied for decades, our understanding has deepened
      since its cloning and subsequent expression, enabling numerous mutational and
      protein engineering studies. SBP, however, has been neglected until recently,
      despite offering a real alternative to HRP: SBP actually outperforms HRP in terms
      of stability and is now used in numerous biotechnological applications, including
      biosensors. Review of both is timely. This article summarizes and discusses the
      main insights into the structure and mechanism of HRP, with special emphasis on
      HRP mutagenesis, and outlines its use in a variety of applications. It also
      reviews the current knowledge and applications to date of SBP, particularly
      biosensors. The final paragraphs speculate on the future of plant heme-based
      peroxidases, with probable trends outlined and explored.

PMID- 16815579
TI  - Engineered chloroplasts as vaccine factories to combat bioterrorism.
AB  - Bacillus anthracis is ideal for making biological weapons, but the licensed
      anthrax vaccine is unsuitable for widespread public administration. Recombinant
      subunit-vaccine candidates offer potential alternatives, and plant-based
      production systems facilitate the inexpensive bulking of target antigens. A
      recent report demonstrates expression of anthrax protective antigen in tobacco
      chloroplasts--this material is immunogenic and protective when injected into
      mice. Provided an economic purification scheme can be developed, this technology
      holds promise for an improved vaccine.

PMID- 16815580
TI  - The effects of the menstrual cycle on social decision making.
AB  - The cyclic change in hormonal profiles between the two main phases of the
      menstrual cycle mediate shifts in mate preference. Males who advertise social
      dominance are preferred over other men by females in the follicular phase of the
      cycle. The present study explored assignment of high or low status resources to
      dominant looking men by females in either phase of the menstrual cycle. Thirteen
      females who reported that they were free from any kind of hormonal intervention
      and experienced a 28 day cycle, were invited to participate in a mock job
      negotiation scenario. Participants were asked to assign either a minimum, low,
      high or maximum social status job package to a series of male 'employees' that
      were previously rated to look either dominant or non-dominant. The results showed
      that during the follicular phase of the cycle participants assigned dominant
      looking men more high status job resources than the non-dominant looking men.
      However, during the luteal phase the participants assigned low status resources
      to the non-dominant looking men. Females are not merely passive observers of male
      status cues but actively manipulate the environment to assign status.

PMID- 16815581
TI  - Effect of environmental stresses on the mean and distribution of individual cell
      lag times of Escherichia coli O157:H7.
AB  - The effect of starvation, heat or acid stress on duration of individual cell lag
      time (tau) and standard deviation (SD) of tau was investigated using Escherichia
      coli O157:H7. Cells were stressed by exposure to acid (pH 3.5), heat (50 degrees
      C), or starvation in either glucose-free mineral medium (MOPS), tryptic soy broth
      (TSB) or Luria broth (LB). Stressed cells were then diluted into wells of a
      Bioscreen plate to obtain single cells per well. Replicate time to detection (td)
      values were obtained using the Bioscreen and used to calculate the tau and SD.
      Significant (P< or =0.05) increases in tau over untreated controls were found for
      the following treatments: 14 days in acid; 2 h of heating; 3 days starvation in
      MOPS; and 2 days starvation in either TSB or LB. The largest increase in tau was
      >2-fold from 2.5 to 5.6 h observed with the heat treatment. MOPS starvation was
      more detrimental to the cells than was acid treatment over the same time period.
      A significant increase in SD was found with 21 days acid treatment, and 2 days
      starvation in either TSB or LB. No significant increase in SD was found for MOPS
      starvation or heat treatment. Lognormal, Gamma, ExtremeValue and Weibull
      distributions were fitted to the tau data using BestFit. The results suggest that
      the Lognormal distribution is suitable for fitting tau data from either stressed
      or unstressed cells.

PMID- 16815582
TI  - The issue of antimicrobial resistance in human medicine.
AB  - Antibiotics are used worldwide in human medicine and agriculture. In many cases
      the use of antibiotics is unnecessary or questionable. Consumption of antibiotics
      is linked to bacterial resistance. In hospitals, most common resistant bacteria
      include methicillin-resistant Staphylococcus aureus, vancomycin-resistant
      enterococci and Gram-negative rods including Enterobacteriaceae and Pseudomonas
      aeruginosa. Vancomycin intermediate and resistant S. aureus, described just
      recently, represent a new treatment challenge. In the community, penicillin and
      macrolide-resistant pneumococci developed several decades ago and are now present
      all over the world. More recently, community-acquired methicillin-resistant S.
      aureus has become a problem in several countries causing skin infections but also
      severe diseases. Resistance to co-trimoxazole in Escherichia coli has changed
      empirical treatment of urinary tract infections, one of the most common causes of
      the visit to the physician's office. Several reports and studies trying to limit
      the use of antibiotics have shown that antimicrobial resistance of bacteria can
      be reversed, but in general the problem is far from being solved. World Health
      Assembly and the European Community Council have recognized the problem of
      antibiotic resistance as a priority. The relationship between agricultural use of
      antimicrobials and antibacterial resistance in humans should be further
      investigated.

PMID- 16815583
TI  - Human herpesvirus 6A decreases the susceptibility of macrophages to R5 variants
      of human immunodeficiency virus 1: possible role of RANTES and IL-8.
AB  - Human herpesvirus 6 (HHV-6) frequently reactivates in human immunodeficiency
      virus 1 (HIV-1) infected patients, and is thought to be a cofactor in AIDS
      progression. Macrophages are targets and reservoirs of HIV-1 and HHV-6; hence,
      they have an important role in dissemination and pathogenesis of these viruses.
      The present study examined the effects of HHV-6 A variant on replication of R5
      variants of HIV-1 in macrophages. For this purpose, HIV-1 replication was
      investigated in macrophages infected with HIV-1 alone or along with HHV-6A. Our
      results demonstrated that HHV-6A significantly suppressed HIV-1 replication in
      coinfected cultures. HHV-6A infection resulted in increased secretion of RANTES
      and IL-8. Experiments with exogenous RANTES and IL-8 revealed that these
      chemokines also significantly suppressed HIV-1 replication in infected
      macrophages. RANTES is able to induce desensitization and internalization of
      CCR5, the chemokine coreceptor of R5 variants. In addition, IL-8 receptor
      activation results in cross-desensitization and cross-internalization of CCR5. We
      found that CCR5 sensitivity and expression level is diminished in HHV-6A-infected
      macrophage cultures compared with uninfected cells. Taken together, our results
      indicate that HHV-6A infection decreases the susceptibility of macrophages to R5
      variants of HIV-1 in which the HHV-6A induced RANTES and IL-8 may have
      importance.

PMID- 16815584
TI  - Immunological equivalence between mouse brain-derived and Vero cell-derived
      Japanese encephalitis vaccines.
AB  - The persistent spread via animal reservoirs urges expanding vaccination programs
      against pathogens like the Japanese encephalitis virus, JEV. The JEV is spreads
      to new areas by domestic as well as by wild animals. Although there is a safe and
      efficient vaccine on the market, this is derived from infected mouse brains, why
      today's situation requires overcoming the potential risk caused by using animal
      tissues. To meet this demand we have developed a Vero cell-derived JEV vaccine,
      using the same virus strain as in the established one. A phase III clinical study
      of the new vaccine has recently been completed with positive outcome. Like the
      established mouse brain-derived vaccine, the Vero cell-derived one is a formalin
      inactivated whole virus vaccine. We here demonstrate the very good agreement in
      immunological tests between the two antigens. The study includes analyses with
      two neutralizing monoclonal antibodies that blocks cell entry at a late stage in
      infection, assumedly interfering with fusion-related refolding in the virus
      fusion protein. It is obvious that the formalin inactivation treatment, with both
      virus preparations, retains these essential vaccine epitopes.

PMID- 16815585
TI  - [Nonpharmacological treatments for osteoporosis].
AB  - OBJECTIVES: Study the effectiveness of nonpharmacological treatments for
      osteoporosis. METHOD: Review and qualitative analysis of the literature
      concerning the effectiveness of nonpharmacological treatments: physical exercise,
      rehabilitation aiming to prevent falls, spinal orthosis, and vertebro- and
      kyphoplasty. RESULTS: The level of evidence of the effectiveness of
      nonpharmacological treatment is unequal on the basis of randomized study. The
      practice of physical exercise by the ambulatory elderly people and home
      rehabilitation for those who have previously fallen prevent the occurrence of
      falls. For institutionalized people, the prevention of falls is achieved by
      multidisciplinary programs. The use of hip protectors to prevent fracture is
      controversial. Physical exercises prevent bone loss after menopause and during
      postmenopausaul and corticosteroid osteoporosis. The effectiveness of
      mobilization after fracture is not documented. Only one study concerning the use
      of spinal orthosis after vertebral fracture reports interesting results for pain
      and disability. No randomized study concerning vertebroplasty or kyphoplasty for
      osteoporotic vertebral fracture is described. CONCLUSION: The nonpharmacological
      treatments of osteoporosis are considered therapeutic means of key importance.
      They aim at the prevention of falls and bone loss and the reduction of disability
      after fracture. Only physical exercise and rehabilitation have been shown to be
      effective in preventing falls or bone loss. Their ability to reduce the incidence
      of fractures remains to be evaluated.

PMID- 16815586
TI  - A comparison of glycemic effects of glimepiride, repaglinide, and insulin
      glargine in type 2 diabetes mellitus during Ramadan fasting.
AB  - Although diabetics may be exempted from Ramadan fasting, many patients still
      insist on this worship. Aim of the present study is to compare the effects of
      glimepiride, repaglinide, and insulin glargine in type 2 diabetics during Ramadan
      fasting on the glucose metabolism. Patients, who were willing to fast, were
      treated with glimepiride (n=21), repaglinide (n=18), and insulin glargine (n=10).
      Sixteen non-fasting control type 2 diabetics matched for age, sex, and body mass
      index were also included. Fasting blood glucose (FBG), post-prandial blood
      glucose (PBG), HbA1c, and fructosamine as well as lipid metabolism were evaluated
      in pre-Ramadan, post-Ramadan, and 1-month post-Ramadan time points. There was no
      significant change from pre-Ramadan in FBG, PBG, and HbA1c variables in fasting
      diabetics at post-Ramadan and 1-month post-Ramadan. However, PBG was found higher
      in non-fasting control diabetics at post-Ramadan and 1-month post-Ramadan (p<0.05
      and p<0.001, respectively). In fructosamine levels, a significant increase was
      noted both in fasting group and non-fasting group at 1-month post-Ramadan (p<0.01
      for all). However, no significant difference was found in the comparison of the
      changes in fructosamine levels between fasting group and non-fasting group. Risk
      of hypoglycemia did not significantly differ between fasting and non-fasting
      diabetics. There was no significant difference between three drug therapies
      regarding glucose metabolism and rate of hypoglycemia. No adverse effects on
      plasma lipids were noted in fasting diabetics. In this fasting sample of patients
      with type 2 diabetes, glimepiride, repaglinide, and insulin glargine did not
      produce significant changes in glucose and lipid parameters.

PMID- 16815587
TI  - Cardiovascular risk factor control among diabetic patients attending community
      based diabetic care clinics in Italy.
AB  - AIM OF THIS STUDY: To describe the extent to which hyperglycemia, hypertension,
      and dyslipidemia are currently detected, treated, and controlled in diabetic
      patients attending a network of urban community-based diabetic care clinics in
      Italy. METHODS: The study population included 1078 consecutive patients with type
      2 diabetes mellitus (47% women, mean age 67.6+/-9.8 years) visited at eight
      diabetic care clinics between 1 and 30 of November 2004. Values of glycosilated
      hemoglobin, blood pressure, and cholesterol subfractions, as well as clinical and
      medication data, were prospectively collected in all cases in a computerized
      database. RESULTS: Despite a high prevalence of hypertension (66.6%), only 29.6%
      of patients met the treatment goal of a systolic blood pressure <130 mmHg, while
      a diastolic blood pressure <80 mmHg was reached by 38.6% of the study cohort.
      Optimal LDL cholesterol values (<100mg/dl) were present in just 25.5% of cases.
      Values of glycosilated hemoglobin <7% were present in 57.8% of patients.
      CONCLUSIONS: We conclude that adherence to current guidelines for cardiovascular
      prevention and cardiovascular risk factor control represent an exception in
      diabetic patients attending community-based diabetic care clinics. Major efforts
      are required to improve the quality of health care currently delivered to
      diabetic patients.

PMID- 16815588
TI  - Moving beyond assumptions to understand abundance distributions across the ranges
      of species.
AB  - The assumption that species are most abundant in the center of their range and
      decline in abundance toward the range edges has a long history in the ecological
      literature. This assumption has driven basic and applied ecological and
      evolutionary hypotheses about the causes of species range limits and their
      responses to climate change. Here, we review recent studies that are taking
      biogeographical ecology beyond previously held assumptions by observing
      populations in the field across large parts of the species range. When these
      studies combine data on abundance, demographics, organismal physiology, genetics
      and physical factors, they provide a promising approach for teasing out
      ecological and evolutionary mechanisms of the patterns and processes underlying
      species ranges.

PMID- 16815589
TI  - Spatial scaling of microbial biodiversity.
AB  - A central goal in ecology is to understand the spatial scaling of biodiversity.
      Patterns in the spatial distribution of organisms provide important clues about
      the underlying mechanisms that structure ecological communities and are central
      to setting conservation priorities. Although microorganisms comprise much of
      Earth's biodiversity, little is known about their biodiversity scaling
      relationships relative to that for plants and animals. Here, we discuss current
      knowledge of microbial diversity at local and global scales. We focus on three
      spatial patterns: the distance-decay relationship (how community composition
      changes with geographic distance), the taxa-area relationship, and the
      local:global taxa richness ratio. Recent empirical analyses of these patterns for
      microorganisms suggest that there are biodiversity scaling rules common to all
      forms of life.

PMID- 16815590
TI  - Genes involved in Dictyostelium discoideum sexual reproduction.
AB  - Macrocyst formation in the cellular slime moulds is a sexual process induced
      under dark and humid conditions. Normal development life cycle in these organisms
      involves proliferation by cell division and, upon starvation, formation of
      multicellular aggregates and fruiting bodies, consisting of spores and stalk
      cells. Macrocyst formation, cell division by binary fission and spore formation
      are thus three alternative modes of reproduction, for which it is of interest to
      understand how a choice is made. The genetic basis of asexual development and
      fruiting body formation is well known, by contrast information on the genetic
      control of sexual reproduction during macrocyst formation is scarce. In
      Dictyostelium discoideum, the most widely used species, several cell-surface
      proteins relevant to sexual cell fusion have been identified using cell fusion
      blocking antibodies, but isolation of the relevant genes has been unsuccessful.
      Analysis of sexually deficient mutants, some of which are normal for asexual
      development, has shown that sexual reproduction is regulated by both specific
      genes and genes that are also involved in asexual development. Reverse genetic
      analysis of 24 genes highly enriched in a gamete-specific subtraction library has
      revealed four genes involved in the regulation of sexual cell interactions. One
      of them was found to be a novel regulator of the cAMP signalling pathway specific
      to sexual development. Studies on the molecular genetic control of the sexual
      cycle will be reviewed and their contribution to our understanding of the
      organization and function of the D. discoideum genome as a whole discussed.

PMID- 16815591
TI  - Outbreak of Acinetobacter genomic species 3 in a Dutch intensive care unit.

PMID- 16815592
TI  - Two new bradykinin-related peptides from the venom of the social wasp
      Protopolybia exigua (Saussure).
AB  - Two bradykinin-related peptides (Protopolybiakinin-I and Protopolybiakinin-II)
      were isolated from the venom of the social wasp Protopolybia exigua by RP-HPLC,
      and sequenced by Edman degradation method. Peptide sequences of Protopolybiakinin
      I and Protopolybiakinin-II were DKNKKPIRVGGRRPPGFTR-OH and DKNKKPIWMAGFPGFTPIR
      OH, respectively. Synthetic peptides with identical sequences to the bradykinin
      related peptides and their biological functions were characterized.
      Protopolybiakinin-I caused less potent constriction of the isolated rat ileum
      muscles than bradykinin (BK). In addition, it caused degranulation of mast cells
      which was seven times more potent than BK. This peptide causes algesic effects
      due to the direct activation of B(2)-receptors. Protopolybiakinin-II is not an
      agonist of rat ileum muscle and had no algesic effects. However,
      Protopolybiakinin-II was found to be 10 times more potent as a mast cell
      degranulator than BK. The amino acid sequence of Protopolybiakinin-I is the
      longest among the known wasp kinins.

PMID- 16815593
TI  - The effects of endomorphins and diprotin A on striatal dopamine release induced
      by electrical stimulation-an in vitro superfusion study in rats.
AB  - The endomorphins (EM1: Tyr-Pro-Trp-Phe-NH2, and EM2: Tyr-Pro-Phe-Phe-NH2) are
      recently discovered endogenous ligands for mu-opioid receptors (MORs) with role
      of neurotransmitters or neuromodulators in mammals. Cessation of their
      physiological action may be effected through rapid enzymatic degradation by the
      dipeptidyl-peptidase IV (DPPIV) found in the brain synaptic membranes. An in
      vitro superfusion system was utilized to investigate the actions of EM1, EM2 and
      specific DPPIV inhibitor diprotin A on the striatal release of dopamine (DA)
      induced by electrical stimulation in rats. The involvement of the different MORs
      (MOR1 and MOR2) in this process was studied by pretreatment with MOR antagonists
      beta-funaltrexamine (a MOR1 and MOR2 antagonist) and naloxonazine (a MOR1
      antagonist). EM1 significantly increased the tritium-labelled dopamine DA release
      induced by electrical stimulation. EM2 was effective only when the slices were
      pretreated with diprotin A. beta-Funaltrexamine antagonized the stimulatory
      effects of both EM1 and EM2. The administration of naloxonazine did not
      appreciably influence the action of EM1, but blocked the action of EM2, at least
      when the slices were pretreated with diprotin A. These data suggest that both EM1
      and EM2 increase DA release from the striatum and, though diprotin A does not
      affect the action of EM1, it inhibits the enzymatic degradation of EM2. The DA
      stimulating action induced by EM1 seems to be mediated by MOR2, while that evoked
      by EM2 appears to be transmitted by MOR1.

PMID- 16815594
TI  - Modifications of platelet from Alzheimer disease patients: a possible relation
      between membrane properties and NO metabolites.
AB  - Alzheimer disease (AD) is a chronic neurodegenerative disorder characterised by a
      progressive loss of memory and cognitive functions. The formation of nitric oxide
      (NO), by astrocytes, has been suggested to contribute to the neurodegnerative
      process. Some studies have described the participation of different isoforms of
      NOS in the progression of AD. The present work was conducted in order to
      investigate the role played by NO and peroxynitrite in platelets from AD
      patients, the possible correlation with Na(+)/K(+)-ATPase activity and the
      intracellular Ca(2+) in the same group of patients as well as the expression of
      NOS isoenzymes and nitrotyrosine as markers of NO synthesis and reactive protein
      nitration. NO production was significantly elevated in the platelets from AD
      patients compared to controls as well as l-arginine/NO-dependent ONOO(-).
      Membrane Na(+)/K(+)-ATPase activity was significantly decreased in patients than
      in controls while intracellular Ca(2+) concentration shows an opposite trend.
      Platelet from AD patients showed a significantly increased 1-[4
      (trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl
      1,3,5-hexatriene (DPH) fluorescence anisotropy compared with controls. Western
      blot analysis using anti-iNOS and eNOS monoclonal antibodies demonstrated that
      both isoforms were detectable in cell lysates as well as nitrotyrosine more
      pronounced in the cell lysates from AD patients than controls. In conclusion, the
      increased expression and activity of nitrergic system may produce platelet
      membrane alteration or vice versa. These modifications may contribute further to
      the neurodegenerative process in AD because the abnormal function of Alzheimer
      platelets play a very important role in the pathogenesis of the disease.

PMID- 16815595
TI  - Occurrence and co-localization of amyloid beta-protein and apolipoprotein E in
      perivascular drainage channels of wild-type and APP-transgenic mice.
AB  - The deposition of the amyloid beta-protein (Abeta) is a hallmark of Alzheimer's
      disease (AD). One reason for Abeta-accumulation and deposition in the brain may
      be an altered drainage along perivascular channels. Extracellular fluid is
      drained from the brain towards the cervical lymph nodes via perivascular
      channels. The perivascular space around cerebral arteries is the morphological
      correlative of these drainage channels. Here, we show that Abeta is
      immunohistochemically detectable within the perivascular space of 25 months old
      wild-type and amyloid precursor protein (APP)-transgenic mice harboring the
      Swedish double mutation driven by a neuron specific promoter. Only small amounts
      of Abeta can be detected immunohistochemically in the perivascular space of wild
      type mice. Cerebrovascular and parenchymal Abeta-deposits were absent. In APP
      transgenic mice, large amounts of Abeta were found in the perivascular drainage
      channels accompanied with cerebrovascular and parenchymal Abeta-deposition. The
      apolipoprotein E (apoE) immunostaining within the perivascular channels did not
      vary between wild-type and APP-transgenic mice. Almost 100% of the area that
      represents the perivascular space was stained with an antibody directed against
      apoE. Here, Abeta co-localized with apoE indicating an involvement of apoE in the
      perivascular clearance of Abeta. Fibrillar congophilic amyloid was not seen in
      wild-type mice. In APP-transgenic animals, congophilic fibrillar amyloid material
      was seen in the wall of cerebral blood vessels but not in the perivascular space.
      In conclusion, our results suggest that non-fibrillar forms of Abeta are drained
      along perivascular channels and that apoE is presumably involved in this
      clearance mechanism. Overloading such a clearance mechanism in APP-transgenic
      mice appears to result in insufficient Abeta-clearance, increased Abeta-levels in
      the brain and the perivascular drainage channels, and finally in Abeta
      deposition. In so doing, our results strengthen the hypothesis that an alteration
      of perivascular drainage supports Abeta-deposition and the development of AD.

PMID- 16815596
TI  - Trypanocidal activity of 5,6-dihydropyran-2-ones against free trypomastigotes
      forms of Trypanosoma cruzi.
AB  - Sixteen 5,6-dihydro-2H-pyran-2-ones were evaluated in in vitro assay against
      trypomastigotes forms of Trypanosoma cruzi, the causative agent of Chagas'
      disease. A structure-activity relationship study (SAR) allowed us to establish
      the relevant structural features for the trypanocidal activity of goniothalamin
      analogues against T. cruzi. In fact, non-natural form of goniothalamin (ent-1)
      was threefold more potent than the natural one (1). In addition, we have
      identified analogues 9 and 10 (both displaying S configuration) as the highest
      potent compounds against T. cruzi with IC50=0.12 and 0.09 mM (IC50 value for
      crystal violet was 0.08 mM) whereas significantly lower toxicities were observed
      when these compounds were evaluated under LLC-MK2 lineage cells (1.38 and 4.89
      mM, respectively). In addition, epoxides derivatives 12 and ent-12 were shown to
      be more potent than the corresponding stereoisomers 2 and ent-2 and non-natural
      argentilactone (ent-3, IC50=0.47 mM) was twofold more potent than natural
      argentilactone (3, IC50=0.94 mM).

PMID- 16815597
TI  - Synthesis and antibacterial activity of various substituted s-triazines.
AB  - Series of substituted-s-triazines (1-22) were synthesized and evaluated for their
      in vitro antibacterial activity against six representative Gram-positive and Gram
      negative bacterial strains. Many compounds have displayed comparable
      antibacterial activity against Bacillus sphaericus and significantly active
      against other tested organisms with reference to streptomycin.

PMID- 16815598
TI  - [Serum markers of non-invasive fibrosis in chronic hepatitis C virus infection].
AB  - MATTER: Liver biopsy is recommended for the management of patients infected by
      hepatitis C virus (HCV) and is currently the gold standard in assessing liver
      histology. It's an invasive test prone to complications with a morbidity rate of
      0.3 to 0.6% and a mortality rate up to 0.05%. Since the last decade, researchers
      developed non invasifs biomarkers of liver fibrosis as an alternative to liver
      biopsy. These scores are based on different algorithms with various combinations
      of biomarkers issued from extra-cellular matrix, serum and cells. CURRENT EVENTS:
      The diagnostic performance of these scores, estimated by the AUROC for
      significant fibrosis (>F2), in patients with chronic hepatitis C reach 0.78 to
      0.90 for the most accurate. In HIV-HCV co-infected patients and patients with
      hepatitis C cirrhosis the diagnostic performance of these scores reach 0.74 to
      0.88 and 0.73 to 0.97 respectively. PERSPECTIVES: Liver fibrosis biomarkers
      constitutes an alternative to liver biopsy due to their non invasive approach,
      their easy reproducibility and accuracy. However, these scores must be used only
      after a validation in multicentric independent studies. The future is based on
      the comparison and validation of these scores after laboratory methods
      standardization.

PMID- 16815599
TI  - [Bluish-brown sclera and ears].

PMID- 16815600
TI  - The use of reflective journals in the promotion of reflection and learning in
      post-registration nursing students.
AB  - The aim of this qualitative case study was to examine the use of reflective
      journals in promoting reflection and learning in post-registration nursing
      students. A purposive homogenous sample of 42 part-time post-registration
      students who had undertaken a module either as part of the Diploma in
      Professional Studies in Palliative Care or Breast Care Nursing within a UK
      University took part in the study. Data were collected from reflective journals
      and interviews. The students' journals were analysed to determine the extent and
      level of reflection using a model devised by Boud [Boud, D., Keogh, R., Walker,
      D. (Eds.), 1985. Reflection: Turning Experience into Learning. Kogan Page,
      London] and adapted by Wong [Wong, F.K.Y., Kember, D., Chung, L.Y.F., Yan, L.,
      1995. Assessing the levels of student reflection from reflective journals.
      Journal of Advanced Nursing 22, 48-57]. A model devised by Mezirow [Mezirow, J.,
      1990. How critical reflection triggers transformative learning. In: Mezirow, J.
      et al. (Eds.), Fostering Critical Reflection in Adulthood: A Guide to
      Transformative and Emancipatory Learning. Jossey-Bass, San Francisco, pp. 1-20;
      Mezirow, J., 1991. Transformative Dimensions of Adult Learning. Jossey-Bass, San
      Franscisco] was used to identify non-reflectors, reflectors and critical
      reflectors. The findings suggest that student writing can be used as evidence for
      the presence or absence of reflective thinking. Evidence also suggests that
      journals are a useful tool for promoting reflection and learning. However, some
      students appear to benefit more from their use than others.

PMID- 16815601
TI  - A review of the quality of life of adult patients treated with long-term
      parenteral nutrition.
AB  - BACKGROUND AND AIMS: Some previous studies have assessed quality of life (QoL) in
      home parenteral nutrition (HPN) using generic instruments or non-validated
      questionnaires. A systematic search of electronic databases and relevant
      publications identified 50 publications. This paper reviews the QoL of patients
      receiving HPN and discusses the factors affecting QoL. RESULTS: There is little
      available data about the QoL of HPN patients. Both HPN and the underlying disease
      may affect QoL, and an evaluation of QoL requires the separation of these two
      issues. CONCLUSIONS: There is a need for a standardised, scientifically
      validated, treatment-specific instrument to measure QoL in this population. The
      use of a treatment-specific QoL questionnaire should become part of the routine
      clinical management of HPN patients.

PMID- 16815602
TI  - Prevalence of antibodies to measles and rubella in Sana'a, Yemen.
AB  - Prevalence of antibodies to measles and rubella was tested in sera collected from
      1368 subjects in urban and rural Sana'a. Overall, 11.7% had no antibodies to
      measles and 14.6% had no antibodies to rubella, despite the fact that measles but
      not rubella vaccine is included in the vaccination program in Yemen. Of 89
      children <5 years of age 49 (55.1%) had no detectable antibodies to measles,
      demonstrating that supplementary measles immunization campaigns are required to
      prevent virus circulation. Assessment of measles immune status among infants in
      the first year of life is required to determine the optimum age for measles
      vaccination. Rubella vaccination should be considered with care in Yemen.

PMID- 16815603
TI  - High prevalence of influenza A virus in ducks caught during spring migration
      through Sweden.
AB  - As part of our ongoing screening of wild birds in Northern Europe, 358 mallards
      (Anas platyrhynchos) and 203 shelducks (Tadorna tadorna) were caught in southern
      Sweden during the spring 2003. Faecal samples were analyzed by real time RT-PCR
      for the presence of influenza A virus. In contrast to what has been found in
      North American studies; Eurasian spring migrating ducks passing through Sweden
      had a relatively high prevalence of influenza A virus.

PMID- 16815604
TI  - An update on malaria prevention, diagnosis and treatment for the returning
      traveller.
AB  - The diagnosis of malaria needs to be considered for every returning traveller
      with a fever. Compliance with prevention, both pharmaceutical and non
      pharmaceutical, is essential for every traveller. New tests for diagnosis are now
      available. Treatment options have recently expanded to include the artemisinin
      derivatives that used to be unavailable in the western countries.

PMID- 16815605
TI  - Comparison of lead residues among avian bones.
AB  - To determine if significant differences exist in lead (Pb) accumulation in
      different bones, especially those most often used for bone-Pb studies in
      wildlife, we compared Pb concentrations in radius, ulna, humerus, femur, and
      tibia of Common Eider (Somateria mollissima); and radius/ulna (combined), femur,
      and tibia of American Woodcock (Scolopax minor). There were no significant
      differences in bone-Pb concentrations among woodcock bones over a wide range of
      Pb concentrations (3-311 microg/g). In eider, where bone-Pb concentrations were
      low (<10 microg/g), leg bones had significantly higher Pb concentrations
      (approximately 30-40%) than wing bones from the same individuals. The variation
      among individual birds was greater than the variation among different bones
      within a bird. Based on our findings, we conclude that one type of bone may be
      substituted for another in bone-Pb studies although the same bone type should be
      analyzed for all birds within a study, whenever possible.

PMID- 16815606
TI  - A review of studies performed to assess metal uptake by earthworms.
AB  - Earthworms perform a number of essential functions in soil; the impacts of metals
      on earthworms are often investigated. In this review we consider the range of
      earthworm species, types of soil and forms of metal for which metal uptake and
      accumulation have been studied, the design of these experiments and the
      quantitative relationships that have been derived to predict earthworm metal body
      burden. We conclude that there is a need for more studies on earthworm species
      other than Eisenia fetida in order to apply the large existing database on this
      earthworm to other, soil dwelling species. To aid comparisons between studies
      agreement is needed on standard protocols that define exposure and depuration
      periods and the parameters, such as soil solution composition, soil chemical and
      physical properties to be measured. It is recommended that more field or
      terrestrial model ecosystem studies using real contaminated soil rather than
      metal-amended artificial soils are performed.

PMID- 16815607
TI  - In situ biomonitoring of the genotoxic effects of mixed industrial emissions
      using the Tradescantia micronucleus and pollen abortion tests with wild life
      plants: demonstration of the efficacy of emission controls in an eastern European
      city.
AB  - Aim of the study was to monitor changes of genotoxic activity of urban air caused
      by an incinerator and a petrochemical plant in Tradescantia micronucleus (Trad
      MCN) and pollen fertility assays with wild plants (Chelidonium majus, Clematis
      vitalba, Cichorium intybus, Linaria vulgaris, Robinia pseudoacacia). While in the
      first sampling period (1997-2000) significantly (on average 80%) more MN were
      found at the polluted site in comparison to controls from a rural area, no
      significant effects were observed during a later period (between 2003 and 2005).
      A similar pattern was observed in the pollen abortion assays in which the most
      pronounced effects were found in chicory and false acacia. The differences of the
      results obtained in the two periods can be explained by a substantial reduction
      of air pollution by use of new technologies. In particular the decrease of SO(2)
      emissions may account for the effects seen in the present study.

PMID- 16815608
TI  - Photoelectrocatalytic degradation of pentachlorophenol in aqueous solution using
      a TiO2 nanotube film electrode.
AB  - Titanium dioxide (TiO2) nanotube film electrodes are fabricated by the anodic
      oxidation method. Scanning electron microscopy (SEM) showed that these tubes were
      well aligned and organized into high-density uniform arrays. XRD analysis showed
      the TiO2 nanotubes to be in the anatase crystal form. The TiO2 nanotube film
      electrode exhibited increased photoelectrocatalytic (PEC) capability compared to
      a traditional TiO2 film electrode fabricated using the anodizing method for
      pentachlorophenol (PCP) degradation in aqueous solution. The bias potential, pH
      value, and electrolyte concentration were shown to be important factors
      influencing the degradation of PCP by the PEC method using the TiO2 nanotube film
      electrode as the working electrode.

PMID- 16815609
TI  - Predicting community sensitivity to ozone, using Ellenberg Indicator values.
AB  - This paper develops a regression-based model for predicting changes in biomass of
      individual species exposed to ozone (RS(p)), based on their Ellenberg Indicator
      values. The equation (RS(p)=1.805-0.118Light-0.135 square root Salinity)
      underpredicts observed sensitivity but has the advantage of widespread
      applicability to almost 3000 European species. The model was applied to grassland
      communities to develop two further predictive tools. The first tool, percentage
      change in biomass (ORI%) was tested on data from a field-based ozone exposure
      experiment and predicted a 27% decrease in biomass over 5 years compared with an
      observed decrease of 23%. The second tool, an index of community sensitivity to
      ozone (CORI), was applied to 48 grassland communities and suggests that community
      sensitivity to ozone is primarily species-driven. A repeat-sampling routine
      showed that nine species were the minimum requirement to estimate CORI within 5%.

PMID- 16815610
TI  - An 'artificial mussel' for monitoring heavy metals in marine environments.
AB  - A new chemical sampling device, artificial mussel (AM), has been developed for
      monitoring metals in marine environments. This device consists of a polymer
      ligand suspended in artificial seawater within a Perspex tubing, and enclosed
      with semi-permeable gel at both ends. Laboratory and field experiments were
      carried out to examine the uptake of five metals (Cd, Cr, Cu, Pb and Zn) by the
      AM. Uptake of metals by AM was proportional to the exposure metal concentrations,
      and the AM was able to accumulate the ASV labile fractions of metals. Uptake and
      release of the metals of AM are similar to those of the mussel Perna viridis, but
      less affected by salinity and temperature. Field studies demonstrated that the AM
      can not only provide a time-integrated estimate of metals concentrations, but
      also allows comparisons of metal levels in different environments and
      geographical areas beyond the natural distribution limits of biomonitors.

PMID- 16815611
TI  - Cadmium and chromium removal kinetics from solution by two aquatic macrophytes.
AB  - The aim of this work was to determine chromium and cadmium bioaccumulation
      processes of two free-floating macrophytes commonly used in wetlands for water
      treatment: Salvinia herzogii and Pistia stratiotes. Metal removal from the
      solution involves two stages: a fast one and a slow one. The fast stage of the Cd
      uptake is significantly different for each species, while it is not significantly
      different in Cr uptake. The most important processes of Cd uptake are biological
      ones in S. herzogii and adsorption, chelation and ionic exchange are in P.
      stratiotes. The main processes of Cr uptake in both macrophytes are adsorption,
      chelation and ion exchange. The slow stage is different for each species and
      metal. Cr precipitation induced by roots occurs in P. stratiotes. Cr uptake
      through leaves is probably the main cause of the increase of Cr in the aerial
      parts of S. herzogii.

PMID- 16815612
TI  - Growth onset, senescence, and reproductive development of meadow species in
      mesocosms exposed to elevated O3 and CO2.
AB  - We studied the effects of elevated O3 (40-50 ppb) and CO2 (+100 ppm) alone and in
      combination on the growth onset, relative chlorophyll meter values, and
      reproductive development of meadow species grown in ground-planted mesocosms
      using open-top chambers. The 3-year study was conducted in the summers of 2002
      2004. Elevated O3 decreased the early season coverage of plant communities and
      delayed the flowering of Campanula rotundifolia and Vicia cracca. The relative
      chlorophyll meter values of Fragaria vesca leaves were decreased by O3. Ozone
      also reduced the overall number of produced flowers, but as far as individual
      species were concerned, O3 had significant effects only on Campanula
      rotundifolia. In the case of Fragaria vesca, O3 decreased the fresh weight of
      individual berries. The effects of CO2 were less pronounced, and CO2 generally
      did not ameliorate the negative effects of O3. Changes in reproduction may affect
      the long-term fate of the whole community.

PMID- 16815613
TI  - Phytotoxicity to and uptake of RDX by rice.
AB  - Phytoremediation is an emerging strategy to remediate soils contaminated with
      pollutants like explosives in which plants will uptake, degrade and/or accumulate
      pollutants. To implement this technology on a site contaminated with RDX, we
      chose rice, which is able to grow in lagoons, and we tested its ability to grow
      in soils with high levels of RDX and to decrease RDX concentrations in soil. Rice
      was grown for 40 days in soil contaminated with increasing [14C]RDX
      concentrations. Emergence and growth were not affected by RDX. Total chlorophyll
      content decreased with RDX concentrations of over 500 mg kg(-1). Amounts of
      chlorophyll were correlated with the appearance of necrosis in leaf extremities.
      After 40 days, rice translocated 89% of uptaken radioactivity to leaves with 90%
      in leaf extremities. Analyzes of leaf extracts showed that 95% of radioactivity
      was RDX in its parent form. Necrosis appears to be a phytotoxic symptom of RDX
      accumulation.

PMID- 16815614
TI  - Distribution of polycyclic aromatic hydrocarbons in thirty typical soil profiles
      in the Yangtze River Delta region, east China.
AB  - Polycyclic aromatic hydrocarbons (PAHs) were quantified in 30 soil profiles from
      the Yangtze River Delta Region, in east China. Relative concentrations of PAH
      compounds with different benzene rings and ratios of fluoranthene to fluoranthene
      plus pyrene and benz(a)anthracene to benz(a)anthracene plus chrysene were used to
      identify the possible sources of soil PAHs. Total concentrations of 15 PAHs in
      topsoils ranged from 8.6 to 3881 microg kg(-1) with an average of 397 microg kg(
      1). Half of the soil samples were considered to be contaminated with PAHs (>200
      microg kg(-1)) and two sampling sites were heavily polluted by PAHs with
      concentrations >1000 microg kg(-1). Phenanthrene was found in soils below a depth
      of 100 cm in half of the sampling sites, but the detectable ratio of
      benzo(a)pyrene decreased sharply from 100% in topsoil to 0 in the 4th horizon.

PMID- 16815615
TI  - Mother-child reminiscing about everyday experiences: implications for
      psychological interventions in the preschool years.
AB  - The preschool years are a critical period for all aspects of child development,
      and any disruption to cognitive or socio-emotional functioning at this stage has
      potential repercussions for current and future functioning. There is, therefore,
      a need for clinical interventions that optimize the functioning of children at
      risk of psychological disorders. In the current paper, we review research showing
      that the way in which parents discuss everyday experiences with their young
      children has significant implications for the children's cognitive and socio
      emotional functioning. Specifically, mothers who engage their child in a rich
      elaborative style of talking about past experiences have children who also
      develop an elaborative style of remembering and reporting personal experiences.
      Evidence suggests that elaborative reminiscing can benefit children's social and
      self understanding, the quality of the parent-child relationship, and language
      and emergent literacy. Moreover, findings show that elements of the elaborative
      style can be identified and taught to parents. We propose that elaborative parent
      child discussion about the past could form the basis of developmentally sensitive
      intervention during the preschool period.

PMID- 16815616
TI  - Efficacy of olanzapine and haloperidol in an animal model of mania.
AB  - PURPOSE: Intracerebroventricular (ICV) administration of ouabain, a potent sodium
      pump inhibitor, has been used to model mania. Antipsychotic agents have
      demonstrated efficacy in the management of acute mania. This study was undertaken
      to determine the prophylactic efficacy of olanzapine and haloperidol in the
      ouabain mania model. METHODS: Male Sprague-Dawley rats (4-8/group) were treated
      with two haloperidol decanoate intramuscular shots one week apart (21 mg/kg) or
      twice daily olanzapine intraperitoneal injections at low dose (1 mg/kg/day) or
      high dose (6 mg/kg/day) for 7 days prior to ICV administration of ouabain. Open
      field locomotion was quantified at baseline and after ouabain administration.
      RESULTS: Ouabain caused a significant increase in open field locomotion (253.7+/
      SEM 55.12 vs control 53.1+/-12.13 squares traversed in 30 min in the olanzapine
      experiments, P<0.05; and 236.5+/-41.42 vs 129.3+/-38.23, P<0.05 in the
      haloperidol experiments). Olanzapine alone at low dose (102.2+/-37.7) or high
      dose (151.2+/-49.2) did not alter open field activity. Low dose olanzapine
      (176.6+/-73.27) but not high dose (307.5+/-167.32) caused a modest reduction of
      the ouabain effect. Haloperidol alone significantly reduced motoric activity
      compared to control (55.6+/-18.0, P<0.05), and prevented ouabain-induced
      hyperactivity (60.3+/-33.1, P<0.05). CONCLUSION: Haloperidol, but not olanzapine,
      demonstrated efficacy in this mania model, but methodological details may have
      reduced the effect of olanzapine.

PMID- 16815617
TI  - Compulsive buying and binge eating disorder--a case vignettes.
AB  - Compulsive buying behaviour has recently received long overdue attention as a
      clinical issue. Aim of this report is to describe treatment of two female
      patients diagnosed with compulsive buying disorder in comorbidity with binge
      eating disorder. In both cases, criteria for diagnosing of other axis I or axis
      II disorder were not present. Fluvoxamine was used in pharmacotherapy, and
      psychodynamic psychotherapy as a psychotherapeutical approach. We conclude that
      fluvoxamine and psychodynamic psychotherapy may be effective in treatment of
      compulsive buyers in comorbidity with binge eating disorder.

PMID- 16815618
TI  - Immunohistochemical localisation of the NK1 receptor in the human amygdala:
      preliminary investigation in schizophrenia.
AB  - The amygdala has a role in the modulation of moods and emotion, processes that
      are known to be affected in people with psychiatric disorders such as
      schizophrenia and depression. The tachykinin NK(1) receptor is known to be
      expressed in the amygdala. However to date, there is limited knowledge of the
      distribution of the NK(1) receptor in this region. This study used
      immunohistochemistry to analyse the distribution of the NK(1) receptor in fixed
      human amygdala tissue in control subjects with no history of psychiatric illness
      and matched subjects with a diagnosis of schizophrenia (n=4 pairs). The NK(1)
      receptor was observed sparsely distributed in cell bodies in all amygdaloid
      nuclei with the basolateral and lateral having a greater relative density of
      NK(1) receptor-immunoreactive cell bodies than the other nuclei. Double labelling
      with antibodies to microtubule associated protein and the NK(1) receptor revealed
      that the NK(1) receptor is expressed by large pyramidal, small stellate and large
      bipolar neurons. Interestingly, the basal nucleus of Meynert, which is just
      dorsal to the amygdala, was observed to have a significantly higher relative
      density of NK(1) receptor-immunoreactive cell bodies compared to any of the
      amygdaloid nuclei. Preliminary analysis of the density of NK(1) receptor
      immunoreactive cell bodies in the major amygdaloid nuclei and the basal nucleus
      of Meynert revealed no significant differences between schizophrenia and control
      subjects. Real-time PCR showed that the mRNA for both the short and long isoforms
      of the NK(1) receptor was expressed at low levels in fresh frozen human amygdala
      tissue from control subjects and that this was not different in matched subjects
      with schizophrenia (n=11 pairs). In conclusion, this study has demonstrated that
      the NK(1) receptor is widely distributed in the amygdala, and has shown for the
      first time a high relative density of NK(1) receptor-immunoreactive cell bodies
      in the basal nucleus of Meynert.

PMID- 16815619
TI  - Pentylenetetrazol-induced kindling seizure attenuated by Ginkgo biloba extract
      (EGb 761) in mice.
AB  - Ginkgo biloba extract (EGb 761) has been used therapeutically for centuries. It
      has attracted great attention as agents for improving circulation, particularly
      cerebral circulation, which may lead to improved mental function. Many researches
      hypothesized on the role of the extract in the treatment of diseases involving
      free radicals and oxidative damage. In the present study, anticonvulsant and
      antioxidant effects of EGb 761 were investigated in pentylenetetrazol (PTZ)
      kindled mice. Valproic acid (VA), a major antiepileptic drug, was also tested for
      comparison. EGb 761-treated mice displayed a significant attenuated response to
      PTZ on the test day (day 26) compared with saline-treated and VA-treated animals.
      Valproic acid significantly increased seizure latency. Pretreatments with EGb 761
      significantly protected against PTZ-induced convulsive behaviors (seizure
      latency, seizure score). EGb 761 and VA significantly decreased PTZ-induced
      oxidative injury in brain tissue. EGb 761 was found to be the most effective in
      preventing PTZ-induced oxidative damage among both substances studied. The data
      obtained support our speculation that neuroprotective action of EGb 761 may
      correlate with its ability to inhibit not only excessive reactive oxygen species
      (ROS) formation but also seizure generation. Taken together, the results of the
      present study show that the effect of EGb 761 on ROS production contributes to
      their neuroprotective action. It might be concluded that the suppression of
      seizure-induced ROS generation may be involved in the mechanism of action of
      antiepileptic drugs.

PMID- 16815621
TI  - Structural insights into protein-uranyl interaction: towards an in silico
      detection method.
AB  - Documenting the modes of interaction of uranyl (UO(2)2+) with large biomolecules,
      and particularly with proteins, is instrumental for the interpretation of its
      behavior in vitro and in vivo. The gathering of three-dimensional information
      concerning uranyl-first shell atoms from two structural databases, the Cambridge
      Structural Databank and the Protein Data Bank (PDB) allowed a screening of
      corresponding topologies in proteins of known structure. In the computer-aided
      procedure, all potentially bound residues from the template structure were
      granted full flexibility using a rotamer library. The Amber force-field was used
      to loosen constraints and score each predicted site. Our algorithm was validated
      as a first stage through the recognition of existing experimental data in the
      PDB. The coherent localization of missing atoms in the density map of an
      ambiguous uranium/uranyl-protein complex exemplified the efficiency of our
      approach, which is currently suggesting the experimental investigation of uranyl
      protein binding site.

PMID- 16815622
TI  - Binding to the high-affinity M-type receptor for secreted phospholipases A(2) is
      not obligatory for the presynaptic neurotoxicity of ammodytoxin A.
AB  - R180, isolated from porcine brain cortex, is a high-affinity membrane receptor
      for ammodytoxin A (AtxA), a secreted phospholipase A(2) (sPLA(2)) and
      presynaptically active neurotoxin from venom of the long-nosed viper (Vipera
      ammodytes ammodytes). As a member of the M-type sPLA(2) receptors, present on the
      mammalian plasma membrane, R180 has been proposed to be responsible for one of
      the first events in the process of presynaptic neurotoxicity, the binding of the
      toxin to the nerve cell. To test this hypothesis, we prepared and analyzed three
      N-terminal fusion proteins of AtxA possessing a 12 or 5 amino acid residue
      peptide. The presence of such an additional "propeptide" prevented interaction of
      the toxin with the M-type receptor but not its lethality in mouse and neurotoxic
      effects on a mouse phrenic nerve-hemidiaphragm preparation. In addition,
      antibodies raised against the sPLA(2)-binding C-type lectin-like domain 5 of the
      M-type sPLA(2) receptor were unable to abolish the neurotoxic action of AtxA on
      the neuromuscular preparation. The specific enymatic activities of the fusion
      AtxAs were two to three orders of magnitude lower from that of the wild type, yet
      resulting in a similar but less pronounced neurotoxic profile on the
      neuromuscular junction. This is in accordance with other data showing that a
      minimal enzymatic activity suffices for presynaptic toxicity of sPLA(2)s to
      occur. Our results indicate that the interaction of AtxA with the M-type sPLA(2)
      receptor at the plasma membrane is not essential for presynaptic activity of the
      toxin. Interaction of AtxA with two intracellular proteins, calmodulin and the
      R25 receptor, was affected but not prevented by the presence of the N-terminal
      fusion peptides, implying that these proteins may play a role in the sPLA(2)
      neurotoxicity.

PMID- 16815623
TI  - Progesterone for the prevention of preterm birth: a critical evaluation of
      evidence.
AB  - A systematic review of the literature identified nine randomised trials that
      evaluated the effects of progestational agents in the prevention of preterm
      delivery. These studies were of variable quality. Meta-analyses showed reductions
      in delivery rates before 37 weeks (OR 0.42, 95% CI 0.31-0.57) and 34 weeks (OR
      0.51, 95% CI 0.34-0.77) as well as in respiratory distress syndrome (OR 0.55, 95%
      CI 0.31-0.96) with progestational agents. A cumulative meta-analysis showed that
      the treatment benefit for the outcome of delivery before 37 weeks exceeded the
      conventional level of statistical significance in 1975 (p<0.01); by 1985, the p
      value was <0.001, and by 2003, it was <0.0001. Another cumulative meta-analysis
      in which the studies were added to the pooled analysis by decreasing quality
      score showed significant benefit even when the analysis was limited to just the
      highest quality trials (OR 0.47, 95% CI 0.33, 0.66, p<0.0001). An exploration of
      the applicability of the effects across various baseline risks using a L'abbe
      plot found that the benefit was consistent across a range of risks. A
      comprehensive review of both trial and observational data on harm did not show
      any demonstrable evidence of harm to mother and baby. Women at high risk of
      preterm birth should be recommended progestational agent therapy.

PMID- 16815624
TI  - Frequency of de novo urgency in 463 women who had undergone the tension-free
      vaginal tape (TVT) procedure for genuine stress urinary incontinence--a long-term
      follow-up.
AB  - BACKGROUND: To determine risk factors for the appearance of de novo urgency
      symptoms, and subsequent accompanying problems, after the tension-free vaginal
      tape (TVT) procedure in women with stress urinary incontinence. METHOD: A
      structured preoperative analysis of the incontinence symptoms was made. A mailed
      questionnaire was distributed to 970 women that underwent the TVT procedure
      between 1995 and 2001. Average follow-up was 5.2 years (range 2-8 years). The
      questionnaire included specific questions on current urinary symptoms and
      incontinence. The disease-specific quality of life instruments IIQ-7 and UDI-6
      were used to compare women with, and those without de novo urgency. RESULTS:
      Seven hundred and sixty women (78.3%) responded and 463 of those were identified
      as genuine stress incontinence preoperatively. De novo urgency occurred in 67
      (14.5%) of the women. The frequency was similar irrespective of duration since
      the TVT procedure. The women that reported de novo urgency symptoms were compared
      with those without symptoms. Risk factors for occurrence of de novo urgency
      symptoms were older age (64.7 years versus 60.9 years; p=0.01), parity (2.6
      versus 2.3; p=0.05), history of cesarean section (9.5% versus 2.5%; odds ratio
      5.4), and history of recurrent urinary infections (29.7% versus 18.8%; odds ratio
      1.6, but non-significant. De novo urgency had a severe impact on quality of life,
      as compared to the remaining study population. CONCLUSION: Old age, parity and
      history of cesarean section were risk factors for de novo urgency after TVT
      surgery. Postoperative de novo urgency symptoms are as bothersome for the patient
      as the preoperative stress urinary incontinence.

PMID- 16815625
TI  - X-ray and neutron scattering studies of the hydration structure of alkali ions in
      concentrated aqueous solutions.
AB  - The presence of ions in water provides a rich and varied environment in which
      many natural processes occur with important consequences in biology, geology and
      chemistry. This article will focus on the structural properties of ions in water
      and it will be shown how the 'difference' methods of neutron diffraction with
      isotopic substitution (NDIS) and anomalous X-ray diffraction (AXD) can be used to
      obtain direct information regarding the radial pair distribution functions of
      many cations and anions in solution. This information can subsequently be used to
      calculate coordination numbers and to determine ion-water conformation in great
      detail. As well as enabling comparisons to be made amongst ions in particular
      groups in the periodic table, such information can also be contrasted with
      results provided by molecular dynamics (MD) simulation techniques. To illustrate
      the power of these 'difference' methods, reference will be made to the alkali
      group of ions, all of which have been successfully investigated by the above
      methods, with the exception of the radioactive element francium. Additional
      comments will be made on how NDIS measurements are currently being combined with
      MD simulations to determine the structure around complex ions and molecules, many
      of which are common in biological systems.

PMID- 16815626
TI  - Partially degraded RNA from bladder washing is a suitable sample for studying
      gene expression profiles in bladder cancer.
AB  - OBJECTIVES: To determine the impact of different levels of RNA degradation on
      gene expression measurements and to ascertain if the gene expression profile
      obtained from bladder washing (BW) correlates to that obtained from the related
      bladder tumour (BT). METHODS: BT and BW RNAs from the same patient were heat
      shocked to obtain three RNA degradation states, which were compared with intact
      RNAs from healthy bladders by using complementary DNA (cDNA) microarrays. All
      samples were amplified by means of a T3N9-based transcription method. In
      addition, four of the differentially expressed genes in microarrays related to
      bladder cancer (KRT20, IGF2, GSN, and CCL2) were analyzed in 36 tumoural and 14
      control BW samples by quantitative reverse transcriptase-polymerase chain
      reaction (qRT-PCR). RESULTS: A high percentage of overlapping differentially
      expressed genes were detected between BT arrays (85-91%) and between BW arrays
      (78-93%). Furthermore, the similarity between BW and BT arrays was relatively
      high and independent of the RNA degradation state (52-60%). Finally, expression
      differences for the four selected genes were confirmed in the vast majority of
      extended BW samples tested by qRT-PCR. CONCLUSIONS: Our results showed that
      partially degraded RNA samples analyzed by cDNA microarrays yielded gene
      expression profiles comparable to those obtained using intact RNA. Moreover, BW
      RNA exhibited gene expression patterns similar to those identified in the BT,
      indicating that BW is an appropriate sample for studying gene expression profiles
      of BT using cDNA microarrays. In addition, qRT-PCR results further support the
      suitability of BW for gene expression profiling and its potential use for routine
      diagnostics.

PMID- 16815627
TI  - Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology:
      present and future.
AB  - OBJECTIVES & METHODS: Diseases of the human urinary tract represent common
      morbidities characterized by a high prevalence in the population of most
      westernized countries. The existence of a significant number of affected patients
      and the recent increase in scientific attention has resulted in various
      experimental and clinical efforts in order to evaluate the mechanisms controlling
      the function of urinary tract organs. This review attempts to describe the
      physiology and pharmacology of phosphodiesterase (PDE) isoenzymes with special
      regard to their (potential) use in disorders of the human urogenital tract.
      RESULTS: The promising clinical data for the orally active phosphodiesterase
      (PDE) inhibitors sildenafil, vardenafil and tadalafil, used in the treatment of
      male erectile dysfunction (MED), has boosted research activities on the
      significance of the cyclic GMP- and cyclic AMP pathway in other genitourinary
      tract tissues, such as the bladder, prostate, ureter, urethra, as well as female
      genital tissues. Based on the more extensive understanding of the pathways
      controlling the function of the male and female urogenital tract, orally
      administered phosphodiesterase inhibitors are considered a logical and
      straightforward approach for treating urological diseases. Due to the unending
      charge to conceive advanced first-line treatments, new therapeutic options taking
      into consideration the cyclic nucleotide signaling have been introduced or might
      be launched in the near future. Upcoming strategies will not only focus on the
      nitric oxide (NO)/cGMP cascade but also on compounds modulating signal
      transduction mediated by cyclic adenosine monophosphate, as well as combined
      agents in order to affect multiple peripheral intracellular targets. CONCLUSIONS:
      The article highlights cGMP- and cAMP-pathways, PDE subtypes and their present or
      putative future clinical significance in urological practice.

PMID- 16815628
TI  - Prostate cancer susceptibility is mediated by interactions between exposure to
      ultraviolet radiation and polymorphisms in the 5' haplotype block of the vitamin
      D receptor gene.
AB  - Vitamin D receptor (VDR) polymorphisms are prostate cancer risk candidates. We
      determined if SNPs in haplotype block sub-regions C2 (SNPs C2-1, G/C(3436), C2-2,
      A/G(3944)) or C1 (C1-1, C/T(20965), C1-2, C/T(30056)) are associated with risk in
      an ultraviolet radiation (UVR)-dependent manner. In men with very low exposure,
      SNPs in both sub-regions were associated with risk. Various haplotypes in
      haplotype block C including G(3436)-A(3944)-C(20965)-C(30056), (G or C)-A-C-C and
      G-A-(C or T)-C were significantly associated with increased risk (odds ratios
      between 1.95 and 2.37). These findings suggest various block C SNPs are
      associated with prostate cancer risk via a mechanism involving exposure to
      sunlight.

PMID- 16815629
TI  - siRNA targeted against HAb18G/CD147 inhibits MMP-2 secretion, actin and FAK
      expression in hepatocellular carcinoma cell line via ERK1/2 pathway.
AB  - HAb18G/CD147 has been identified as a factor that induces MMPs production. SiRNA
      targeted against HAb18G/CD147 was transfected into FHCC-98 cells (a HCC cell
      line) to knockdown its expression. The results showed that downregulating
      HAb18G/CD147 decreased ERK1/2, MMP-2 and FAK levels and inhibited cell motility
      and invasion, together with rearranged actin stress fiber formation, while had no
      effects on integrin alpha3beta1 expression. MEK1/2 inhibitor, U0126, inhibited
      MMP-2, FAK and actin expression in FHCC-98 cell line. The findings indicate that
      si-HAb18G inhibits gelatinase production, actin and FAK expression in FHCC-98 via
      an ERK1/2 signaling pathway.

PMID- 16815630
TI  - Erythropoietin in the cerebrospinal fluid in neurodegenerative diseases.
AB  - Erythropoietin (EPO) and its specific receptor (EPOR) have been proposed to act
      as an endogenous system protecting against neuronal injury and neurodegeneration.
      We measured EPO in cerebrospinal fluid (CSF) of patients with neurodegenerative
      diseases, and tested for a correlation with an established biomarker of neuro
      axonal damage, tau protein. Patients with Alzheimer's disease (AD, N=40),
      vascular dementia (VD, N=19), frontotemporal lobe dementia (FTLD, N=5), ALS
      (N=30) and controls (N=49) were included. Cerebrospinal fluid and serum levels of
      EPO and tau were measured using ELISA techniques. We found CSF EPO in ALS to be
      lower than in controls (p=0.04), while no difference between patients with AD,
      VD, FTLD and controls was detectable. CSF EPO correlated with age (p<0.001) as
      well as with tau protein (p=0.002) in all patients pooled. In contrast to the
      upregulation of the EPO/EPOR system in brain tissue upon various conditions of
      neuronal distress, CSF EPO concentrations in neurodegenerative disease were found
      in the same range or even reduced as compared to controls. This may be due to a
      relative deficiency of endogenous CNS EPO in these conditions and/or to a more
      efficient extraction of free EPO molecules from brain intercellular fluid by
      increased numbers of EPOR.

PMID- 16815631
TI  - Modulation of transcallosally mediated motor inhibition in children with
      attention deficit hyperactivity disorder (ADHD) by medication with
      methylphenidate (MPH).
AB  - Motor hyperactivity is one of the most outstanding symptoms of attention deficit
      hyperactivity disorder (ADHD) which might be caused by a disturbed inhibitory
      motor control. Using focal transcranial magnetic stimulation (TMS) we tested the
      cortico-callosal inhibition (duration and latency of the ipsilateral Silent
      Period, iSP) in 23 children with ADHD (mean age 11+/-2.6 years) before and on
      treatment with methylphenidate (MPH). iSP latency was age correlated, whereas iSP
      duration as well as Conners scores were age independent. Analyses of mean
      differences revealed a significant prolongation of iSP duration (p=0.001),
      shortening of iSP latency (p=0.027) and reduction of Conners score (p=0.001)
      under medication. Increase of iSP duration and reduction of Conners score under
      medication were significantly correlated (t=-9.87, p=0.016). Reduced iSP duration
      and prolonged iSP latency in ADHD children could be the result of a disturbed
      transcallosally mediated inhibition, most probable due to a combination of
      maturation deficits of callosal fiber tracts as well as neuronal synaptical
      transmission within the neuronal network between ipsilaterally stimulated cortex
      layer III--the origin of transcallosal motor-cortical fibers--and contralateral
      layer V, the origin of the pyramidal tract. MPH may indirectly improve the
      dysbalance between excitatory and inhibitory interneuronal activities of this
      neuronal network via dopaminergic modulatory effects of the striato-thalamo
      cortical loop.

PMID- 16815632
TI  - Association of corticotropin-releasing hormone receptor1 gene SNP and haplotype
      with major depression.
AB  - The dysregulation of the activity of the hypothalamic-pituitary-adrenocortical
      (HPA) axis system is one of the major neuroendocrine abnormalities in major
      depression (MD). Many pieces of evidence supported that corticotropin-releasing
      hormone (CRH) play a role in the pathophysiology of major depression. In this
      article, whether genetic variations in the corticotropin-releasing hormone
      receptor1 (CRHR1) gene might be associated with increased susceptibility to major
      depression was studied by using a gene-based association analysis of single
      nucleotide polymorphisms (SNPs). Three SNPs were identified in CRHR1 gene and
      genotyped in the samples of patients diagnosed with major depression and matched
      controls. We observed significant allele (P=0.0008) and genotype (P=0.0002)
      association with rs242939, and the haplotype defined by alleles G-G-T for the
      represent rs1876828, rs242939 and rs242941 was significantly over-represented in
      major depression patients compared to controls. These results support the idea
      that the CRHR1 gene is likely to be involved in the genetic vulnerability for
      major depression.

PMID- 16815633
TI  - Participation of the subfornical nucleus in hypothalamic-neurohypophyseal axis
      activation during the early phase of endotoxic shock.
AB  - During the early phase of endotoxic shock the hypothalamus is activated and
      neurohypophyseal hormone secretion is increased. In order to study the
      participation of the subfornical organ (SFO) in this response we lesioned the
      nucleus and determined hormone secretion and c-fos expression in the
      paraventricular and supraoptic nuclei after administration of lipopolysaccharides
      (LPS) in rats. LPS significantly increased the number of cells showing Fos
      immunoreactivity in the paraventricular and supraoptic nuclei of the hypothalamus
      (p < 0.05) and also caused an increase in plasma levels of vasopressin and
      oxytocin (p < 0.05). SFO lesion significantly reduced LPS-induced Fos
      immunoreactivity (p < 0.05) and hormone secretion (p < 0.05). We conclude that
      the SFO participates in the activation of the hypothalamic-neurohypophyseal axis
      in the early phase of endotoxic shock.

PMID- 16815634
TI  - Estradiol prevents the injury-induced decrease of Akt/glycogen synthase kinase
      3beta phosphorylation.
AB  - Estradiol prevents neuronal cell death through the activation of cell survival
      signals and the inhibition of apoptotic signals. This study investigated whether
      estradiol modulates the anti-apoptotic signal through the phosphorylation of Akt
      and its downstream target, glycogen synthase kinase 3beta (GSK3beta). Adult
      female rats were ovariectomized and treated with estradiol prior to middle
      cerebral artery occlusion (MCAO). Brains were collected 24 h after MCAO and
      infarct volumes were analyzed. Estradiol administration significantly reduced
      infarct volume and decreased the positive cells of TUNEL staining in the cerebral
      cortex. Potential activation was measured by phosphorylation of Akt at Ser(473)
      and GSK3beta at Ser(9) using Western blot analysis and immunohistochemistry.
      Estradiol prevented the injury-induced decrease of pAkt and pGSK3beta.
      Furthermore, pretreatment with estradiol decreased glutamate toxicity-induced
      cell death in a hippocampal cell line (HT22). Also, estradiol prevented the
      glutamate toxicity-induced decrease of pAkt and pGSK3beta in HT22 cells. Our
      findings suggest that estradiol plays a potent protective role against brain
      injury and that phosphorylation of Akt and GSK3beta by estradiol mediated these
      protective effects.

PMID- 16815635
TI  - A 38-kDa protein from Babesia gibsoni and its antibody response in an
      experimentally infected dog.
AB  - A cDNA encoding the Babesia bovis 12D3 antigen homologue was obtained by
      immunoscreening the expression library prepared from Babesia gibsoni merozoite
      mRNA. The complete nucleotide sequence of the gene was 1406 bp. Computer analysis
      suggested that the sequence contains an open reading frame of 1052 bp encoding an
      expected protein with a molecular weight of 36kDa. Based on homology analysis,
      this putative protein was designated as the B. gibsoni 12D3 antigen (Bg12D3). The
      Bg12D3 gene was expressed in the Escherichia coli BL21 strain, and the
      chronically infected dog serum reacted with the recombinant protein. The
      antiserum against the recombinant Bg12D3 protein can recognize a 38-kDa native
      protein, which is consistent with its expected size. Moreover, the purified
      recombinant proteins were used as the antigen to detect the antibody response in
      an experimentally infected dog by the enzyme-linked immunosorbent assay (ELISA).
      Our results indicated that the Bg12D3 protein was recognized by the host immune
      system and that it induced an antibody response in chronic B. gibsoni infection.
      These results allowed us to identify a new member of the 12D3 antigens and its
      characteristic immune response in canine B. gibsoni infection.

PMID- 16815636
TI  - Comparison of detection methods for Toxoplasma gondii in naturally and
      experimentally infected swine.
AB  - Results from recent serological surveys and epidemiological studies show that
      pigs raised in a variety of management systems can be carriers of the tissue cyst
      stage of Toxoplasma gondi. This parasite can be transmitted to humans through the
      consumption of improperly prepared pork, making detection and removal of infected
      swine carcasses from the food chain an important food safety issue. Several
      methods are available for detection of T. gondii infected swine, including
      serological assays, polymerase chain reaction, and animal bioassays. The aim of
      the present study was to compare the detection sensitivities of six of these
      commonly used methods for detection of T. gondii infection in tissues from
      naturally and experimentally infected pigs. The results indicate that a serum
      based ELISA is the most sensitive method, of those tested, for detection of T.
      gondii infected swine.

PMID- 16815637
TI  - Compatibility of the fungus Metarhizium anisopliae and deltamethrin to control a
      resistant strain of Boophilus microplus tick.
AB  - The tick Boophilus microplus causes economic impact to cattle producers and has a
      great capacity to develop resistance to chemical acaricides. It is very important
      the development of new techniques to complement the control of this parasitosis.
      Biological control is a promising option to maintain acceptable levels of tick
      populations in cattle. Therefore, the present study evaluated the association of
      deltamethrin and the entomopathogenic fungus Metarhizium anisopliae against B.
      microplus larvae resistant to pyrethroid. The synthetic pyrethroid, deltamethrin,
      was used at concentrations of 0.39, 0.78, 1.56, 3.12 and 6.12 ppm, M. anisopliae
      was used at concentrations of 10(5), 10(6), 10(7) and 10(8) conidia ml(-1). Their
      associations were also evaluated in in vitro tests. The assays showed that the
      tick strain is resistant to deltamethrin, but high mortality rates were observed
      when deltamethrin was associated with the entomopathogen. The larvae's mortality
      rates ranged from 7 to 36.5% for the different concentrations of deltamethrin,
      however, for the different concentrations of M. anisopliae, the mortality rates
      ranged from 10 to 96.9%. Mortality rates were proportional to the concentrations
      used for both deltamethrin and the fungus. Predominantly, the association of
      pyrethroid and fungus resulted in higher larvae mortalility rates than those
      obtained with the respective non-associated concentrations. Thus, the present
      study indicates that this association can be used as a tool for integrated
      control of the tick B. microplus.

PMID- 16815638
TI  - Substance abuse in Iranian high school students.
AB  - Adolescent substance abuse potentially holds a number of negative implications
      for the health and well-being of the individual, including increased risk for
      injury and death from interpersonal violence, motor vehicle accidents, and
      drowning, increased probability of engaging in high risk sexual behaviors; and
      increased risk for suicidal ideation and behaviors. The aim of this paper is to
      estimate prevalence of substance abuse among the sample of 10th grade male
      students in Tabriz City, and to evaluate the associated factors. Of all 10th
      grade male students in Tabriz, Iran, 1785(13.7%) were randomly sampled. Mean age
      of the subjects was 16.3+/-0.87 years. A self-administered questionnaire was used
      to collect demographic data, substance abuse, smoking status and friends smoking.
      The influence of different factors on substance abuse was evaluated with a
      logistic regression model. Among 1785 students 226 (12.7%, 95% CI: 11.2-14.3) had
      ever used alcohol and 36 (2.0%, 95% CI: 1.5-2.8) had used drugs. The results
      indicate that older age (OR=1.55), having general risk taking behavior (OR=1.70),
      higher smoking stage (OR=3.70), having self-injury (OR=1.22), higher
      socioeconomic class (OR=1.62), and ever use of illicit drugs (OR=5.72) were
      factors associated with student's ever use of alcohol. This study has shown low
      prevalence of substance abuse and determined some of its risk factors among
      students. More studies about adolescent population are necessary to approve the
      observed results of this study and thus allow for a certain generalization of the
      observations.

PMID- 16815639
TI  - Anthelmintic activity of Swertia chirata against gastrointestinal nematodes of
      sheep.
AB  - This paper describes in vitro and in vivo anthelmintic activities of Swertia
      chirata. In vitro studies revealed that at 25 mg/ml (P>/=0.05) the crude aqueous
      (CAE) and methanolic extracts (CME) of S. chirata whole plant showed an
      anthelmintic effect on live Haemonchus contortus. Moreover, in the in vivo study,
      the whole plant of S. chirata administered as crude powder (CP), CAE and CME at
      the dose of 3 g/kg to sheep naturally infected with mixed species of
      gastrointestinal nematodes, showed a significant reduction in egg per gram of
      faeces.

PMID- 16815640
TI  - Linarin, a selective acetylcholinesterase inhibitor from Mentha arvensis.
AB  - Linarin (acacetin-7-O-beta-d-rutinoside) from the flower extract of Mentha
      arvensis showed selective dose dependent inhibitory effect on
      acetylcholinesterase.

PMID- 16815641
TI  - Relaxant effect of aqueous extract of Cistus ladaniferus on rodent intestinal
      contractions.
AB  - The effects of the aqueous extract of Cistus ladaniferus leaves and stems were
      studied on the rodent isolated jejunum. The extract produced a reversible
      concentration dose-dependent (0.1-3 mg/ml) inhibition of the spontaneous motility
      of the rabbit jejunum. The inhibitory effects of the extract were not affected by
      pretreatment with the inhibitors of the alpha and beta adrenergic receptors
      yohimbine, prazosin or propranolol. The extract also inhibited K(+)-induced
      contractions in rabbit and rat jejunum at a similar concentration range. This
      result suggests that the antispasmodic action of the extract is mediated through
      calcium channel blockade. The results confirm the traditional use of C.
      ladaniferus in treating intestinal ache.

PMID- 16815642
TI  - The BCL6 proto-oncogene: a leading role during germinal center development and
      lymphomagenesis.
AB  - The BCL6 proto-oncogene encodes a nuclear transcriptional repressor, with pivotal
      roles in germinal center (GC) formation and regulation of lymphocyte function,
      differentiation, and survival. BCL6 suppresses p53 in GCB-cells and its
      constitutive expression can protect B-cell lines from apoptosis induced by DNA
      damage. BCL6-mediated expression may allow GCB-cells to sustain the low levels of
      physiological DNA breaks related to somatic mutation (SM) and immunoglobulin
      class switch recombination which physiologically occur in GCB-cells. Three types
      of genetic events occur in the BCL6 locus and involve invariably the 5' non
      coding region and include translocations, deletions and SM actively targeted to
      the 5' untranslated region. These acquired mutations occur independently of
      translocations but may be involved in the deregulation of the gene and/or
      translocation mechanisms. The favorable prognostic value of high levels of BCL6
      gene expression in NHL seems well-established. By contrast, the relevance of SM
      or translocation of the gene remains unclear. However, it is likely that non
      Hodgkin's lymphomas (NHL) harboring the most frequent translocation involving
      BCL6, i.e. t(3;14), are characterized by a common cell of origin and similar
      oncogenic mechanisms. Several experiments and mouse models mimicking BCL6
      translocation occurring in human lymphoma have demonstrated the oncogenic role of
      BCL6 and constitute a rational to consider BCL6 as a new therapeutic target in
      NHL. BCL6 blockade can be achieved by different strategies which include siRNA,
      interference by specific peptides or regulation of BCL6 acetylation by
      pharmacological agents such as SAHA or niacinamide and would be applicable to
      most type of B-cell NHL.

PMID- 16815643
TI  - [Biochemical profile of fetal blood sampled by cordocentesis in 35 pregnancies
      complicated by growth retardation].
AB  - AIM OF THE STUDY: Intra-uterine growth retardation (IUGR) is a frequent pathology
      in obstetrics characterized by high heterogeneity. Fetal smallness is sometimes
      constitutional, but can also be accompanied by fetal distress and vital risks for
      the infant. In 35 pregnancies complicated by IUGR of different etiologies, we
      measured on fetal blood obtained by cordocentesis, biochemical variables
      characteristic of the fetuses' respiratory and metabolic status. The aim of the
      study was to identify the discriminative biological alterations, related to
      growth retardation and fetal distress. PATIENTS AND METHODS: The studied
      population includes 27 cases of severe IUGR, of gestational age 30,2+/-4,6 weeks
      of gestation (WG) (divided into 20 cases of isolated IUGR and 7 cases of IUGR
      associated with malformative syndrome), as well as 8 cases of moderate IUGR, of
      gestational age 26+/-4,5 WG; all fetuses had normal karyotypes. A group of 73
      normal fetuses, of gestational age 26,3+/-5,7 WG, constituted a reference
      population. PH, pCO(2), bicarbonate concentration, pO(2) and SaO(2), as well as
      glucose, pyruvate, lactate, free fatty acids, aceto-acetate, beta-hydroxybutyrate
      and cholesterol concentrations were measured on umbilical venous blood (UVB).
      RESULTS: In case of severe but isolated growth retardation, UVB analysis showed
      the frequency of acid-base and gasometric disturbances: acidemia and hypoxemia
      (65% of cases), hypercapnia (60% of cases). Metabolic abnormalities were shown:
      decrease in glycemia (35% of cases), increase in pyruvatemia and lactatemia (40%
      of cases), increased free fatty acids serum concentration; a diminution of
      umbilical venous cholesterol level, the most frequent abnormality, can be seen in
      70% of fetuses. In case of severe IUGR associated with malformative syndrome, UVB
      acid-base and metabolic changes were rarely seen; however, UVB cholesterol level
      is low in some cases. In case of growth retardation classified as moderate,
      modifications are relatively not frequent and essentially gasometric. CONCLUSION:
      In about 60% of cases of severe and isolated IUGR, there is a risk of fetal
      distress, related to an alteration of the transplacental transfer of respiratory
      gases and nutritional substrates; chronic fetal malnutrition can be involved,
      with an impact on the growth of the fetus. In case of IUGR associated with
      malformative syndrome, fetal smallness is probably a result of intrinsic fetal
      damage, without nutritional origin.

PMID- 16815644
TI  - Dog paw preference shows lability and sex differences.
AB  - Paw preferences in domestic dogs were studied using three different behavioural
      tests, recording frequency, duration and latency of paw use. No overall
      population tendency to right- or left-paw preference was seen on any of the
      tests, nor could a sub-population of handed dogs be detected. This failure to
      replicate previous reports that male dogs tend to use their left paws while
      females use their right was counterbalanced by a significant tendency for male
      dogs to use their left paw when initially presented with one test, and for the
      latency of left paw use to be significantly shorter than that for right paw use
      on these initial presentations. This significant effect disappeared with repeated
      presentation of the test, and was not present in females. We conclude that
      behavioural lateralisation appears to be a labile category in dogs, and may be
      related to brain hemispheric effects in responding to novel stimuli.

PMID- 16815645
TI  - Social relationships in a herd of Sorraia horses Part I. Correlates of social
      dominance and contexts of aggression.
AB  - Factors related to dominance rank and the functions of aggression were studied in
      a herd of Sorraia horses, Equus caballus, under extensive management. Subjects
      were 10 adult mares 5-18 years old and a stallion introduced into the group for
      breeding. Dominance relationships among mares were clear, irrespective of rank
      difference, and remained stable after introduction of the stallion. The dominance
      hierarchy was significantly linear and rank was positively correlated with age
      and total aggressiveness. Higher-ranking mares received lower frequency and
      intensity of agonistic interactions. Nevertheless, higher-ranking dominants were
      not more likely to elicit submission from their subordinates than lower-ranking
      dominants. Neither close-ranking mares nor mares with less clear dominance
      relationships were more aggressive towards each other. Agonistic interactions
      seemed to be used more importantly in regulation of space than to obtain access
      to food or to reassert dominance relationships. Contexts of aggression were
      related to mare rank. The results suggest that dominance relationships based on
      age as a conventional criterion were established to reduce aggressiveness in a
      herd where the costs of aggression are likely to outweigh the benefits.

PMID- 16815646
TI  - Mammalian Polycomb complexes are required for Peyer's patch development by
      regulating lymphoid cell proliferation.
AB  - The vertebrate Polycomb Group (PcG) genes encode proteins that form large
      multimeric and chromatin-associated complexes implicated in the stable repression
      of developmentally essential genes. Rnf110 and Phc2 are shown to be components of
      mammalian PcG multimeric complexes in HeLa cells. Here we report defects in
      Peyer's patch (PP) development in Rnf110 mutant mice, which is synergically
      exaggerated by Phc2 mutation. PP development involves a series of inductive
      interactions and subsequent differentiation and proliferation between lymphoid
      and mesenchymal cells in late gestational stage. Rnf110 and Phc2 mutations impair
      development of PP anlagen by affecting proliferation of lymphoid lineage cells
      populated in PP anlagen in gene-dosage dependent manner. We suggest that PcG
      complexes may act to mediate certain inductive signals maybe through IL-7Ralpha
      to allow sufficient proliferation of lymphoid inducer cells during PP
      organogenesis.

PMID- 16815647
TI  - Identification and characterization of NYGGF4, a novel gene containing a
      phosphotyrosine-binding (PTB) domain that stimulates 3T3-L1 preadipocytes
      proliferation.
AB  - A novel gene named NYGGF4, which was expressed at a higher level in obese
      subjects, was isolated and characterized. It is a 1527-bp cDNA, containing 753
      nucleotides of an ORF (open reading frame) predicting 250 amino acids with a
      molecular mass of 28.27 kDa. Amino acid sequence analysis revealed NYGGF4 has a
      phosphotyrosine-binding (PTB) domain. Northern blot analysis revealed NYGGF4 is
      expressed primarily in adipose tissue, heart, and skeletal muscle but not in any
      other tissue examined. Confocal imagery analyses with green fluorescent protein
      tagged protein transiently expressed in 3T3-L1 preadipocytes and 293-T cells show
      that NYGGF4 localizes in the cytoplasm. Furthermore, ectopic expression of NYGGF4
      dramatically increases the proliferation of 3T3-L1 peadipocytes without affecting
      adipocytic differentiation. And the NYGGF4 expression 3T3-L1 cells had a greater
      number of cells in S-phase. Our data suggest that NYGGF4 might be a signaling
      molecule and could play a role in cell growth and adipogenesis process.

PMID- 16815648
TI  - PCR-based detection reveals no causative role for Mycoplasma and Ureaplasma in
      feline lower urinary tract disease.

PMID- 16815649
TI  - Impact of volume guarantee ventilation on arterial carbon dioxide tension in
      newborn infants: a randomised controlled trial.
AB  - OBJECTIVE: To compare the effects of the two modes of ventilation, synchronous
      intermittent positive pressure ventilation (SIPPV) and SIPPV with Volume
      Guarantee (VG), on arterial carbon dioxide tension (PaCO(2)) immediately after
      neonatal unit admission. STUDY DESIGN: Randomised study of ventilation mode for
      premature inborn infants admitted to two tertiary neonatal units. After
      admission, infants were randomised to receive either SIPPV or VG using a Drager
      Babylog 8000 plus ventilator. In the SIPPV group, peak airway pressure was set
      clinically. In the VG group, desired tidal volume was set at 4 ml/kg, with the
      ventilator adjusting peak inspiratory pressure to deliver this volume. The study
      was completed once the first arterial PaCO(2) was available, with the desirable
      range defined as 5-7 kPa. RESULTS: PaCO(2) was significantly higher in the VG
      group (VG: 5.7 kPa, SIPPV: 4.9 kPa; p=0.03). The VG group had fewer out-of-range
      PaCO(2) values (VG: 42%, SIPPV: 57%) and fewer instances of hypocarbia <5 kPa
      (VG: 32%, SIPPV: 57%) but neither difference achieved statistical significance.
      Regression analysis showed PaCO(2) was negatively correlated with gestation (r=
      0.41, p=0.01) and also with the mode of ventilation (r=0.32, p<0.05). In the VG
      group, all infants 23-25 weeks' gestation had out-of-range PaCO(2) values. VG
      significantly reduced the incidence of out-of-range PaCO(2) and hypocarbia in
      infants over 25 weeks' gestation (VG: 27%, SIPPV: 61%; p<0.05). CONCLUSION: Using
      this strategy, VG appears feasible in the initial stabilisation of infants over
      25 weeks' gestation, with a halving of the incidence of hypocarbia. In the small
      number of babies studied below this gestation, VG was not found to be effective.

PMID- 16815650
TI  - Luteal blood flow and progesterone production in mares.
AB  - The temporal relationships between blood flow in the corpus luteum (CL) and
      circulating progesterone concentrations were studied in 20 mares. Retrospective
      inspection of plasma progesterone concentrations indicated that a precipitous
      decrease occurred during Days 15-17 (Day 0 = ovulation) and was defined as the
      luteolytic period. Mean percentage of CL with color-Doppler signals for blood
      flow was maximum on Day 10 (77.3%), and Days 10-14 (49.8%) were defined as the
      preluteolytic period. The cross-sectional area of the CL decreased progressively
      from Day 4 (9.0 cm2) to Day 19 (1.5 cm2). Progesterone reached maximum
      concentration on Day 8 (12.8 ng/ml) and thereafter CL area and plasma
      progesterone decreased in parallel until the onset of luteolysis. During the
      luteolytic period, the decrease in plasma progesterone was about sixfold greater
      than during the preluteolytic period, whereas the decrease in CL area and in
      percentage of CL with blood-flow area were about twofold greater. There was no
      indication that an acute increase or decrease in luteal blood flow occurred prior
      to the precipitous decrease in plasma progesterone.

PMID- 16815651
TI  - Prior hormone therapy and breast cancer risk in the Women's Health Initiative
      randomized trial of estrogen plus progestin.
AB  - OBJECTIVES: To assess the extent to which prior hormone therapy modifies the
      breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health
      Initiative (WHI) randomized trial. METHODS: Subgroup analyses of prior hormone
      use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI
      randomized trial of E+P over an average 5.6 years of follow-up. RESULTS: Small
      but statistically significant differences were found between prior HT users and
      non-users for most breast cancer risk factors but Gail risk scores were similar.
      Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by
      prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus
      placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly
      different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77
      1.36). The interaction between study arm and follow-up time was significant
      overall (p=0.01) and among never users (p=0.02) but not among prior users
      (p=0.10). The cumulative incidence over time for the E+P and placebo groups
      appeared to cross after about 3 years in prior users, and after about 5 years in
      women with no prior use. No interaction was found with duration (p=0.08) or
      recency of prior use (p=0.17). Prior hormone use significantly increased the E+P
      hazard ratio for larger, more advanced tumors. CONCLUSION: A safe interval for
      combined hormone use could not be reliably defined with these data. However, the
      significant increase in breast cancer risk in the trial overall after only 5.6
      years of follow-up, initially concentrated in women with prior hormone exposure,
      but with increasing risk over time in women without prior exposure, suggests that
      durations only slightly longer than those in the WHI trial are associated with
      increased risk of breast cancer. Longer-term exposure and follow-up data are
      needed.

PMID- 16815652
TI  - Relationship between drug dissolution and leaching of plasticizer for pellets
      coated with an aqueous Eudragit S100:L100 dispersion.
AB  - In order to investigate the relationship between drug dissolution and leaching of
      plasticizer, theophylline pellets coated with 30% (w/w) Eudragit S100:L100 (1:1)
      plasticized with different levels of triethyl citrate (TEC) were prepared. The
      influence of storage conditions on the dissolution profile of theophylline and
      leaching of TEC was determined. Theophylline was found to dissolve completely
      from pellets coated with Eudragit S100:L100 (1:1) plasticized with 50% TEC at pH
      6.0 after 2h. The shape of the pellets was maintained during dissolution testing.
      Cracks due to the leaching of TEC were observed in the scanning electron
      micrographs (SEMs) following dissolution testing at pH 6.0. Both the dissolution
      of theophylline and the leaching of TEC decreased during storage due to further
      coalescence of the acrylic polymers. The dissolution profiles of theophylline
      showed a biphasic pattern and the lag times were estimated as the time points at
      which a second, rapid release of theophylline was initiated. Subsequently, the
      percent of TEC leached at the lag time was calculated. While the lag time was
      increased by storage time and humidity, the percent of TEC leached at the lag
      time was unchanged as a function of storage condition and was dependent on the
      initial TEC levels in the films. In conclusion, the plasticizer content in the
      film coating influenced the dissolution profile of theophylline from pellets
      coated with Eudragit S100:L100 (1:1). A large amount of the TEC was leached from
      the enteric films before drug release was initiated and a TEC level of
      approximately 30% in the films, based on the polymer weight, was the critical
      amount of TEC for initiating drug release during dissolution testing at pH 6.0.
      While enteric films are more soluble and dissolve faster at higher pH values, the
      kinetics of plasticizer release was one of the important factors controlling the
      dissolution of drugs at pH 6.0, at which pH the enteric polymers were insoluble.

PMID- 16815653
TI  - Topochemical models for the prediction of permeability through blood-brain
      barrier.
AB  - Relationship between the topochemical indices and permeability of diverse series
      of compounds through blood-brain barrier has been investigated. Three
      topochemical indices, Wiener's topochemical index--a distance-based topochemical
      descriptor, molecular connectivity topochemical index--an adjacency based
      topochemical descriptor and eccentric connectivity topochemical index--an
      adjacency-cum-distance based topochemical descriptor, were used for the present
      investigation. A data set comprising of 28 compounds with established CNS
      permeation tendency was selected for present study. The values of all the three
      topochemical indices in the original as well as in the normalized form for each
      of the 28 compounds comprising the data set were computed using an in-house
      computer program. Resultant data was analyzed and suitable models were developed
      after identification of the permeable ranges. Subsequently, permeability
      characteristic was assigned to each compound involved in the data set using these
      models, which was then compared with the reported permeability through blood
      brain barrier. Accuracy of prediction was found to vary from a minimum of 83% to
      a maximum of approximately 95% using these models.

PMID- 16815654
TI  - Physicochemical and in vitro deposition properties of salbutamol
      sulphate/ipratropium bromide and salbutamol sulphate/excipient spray dried
      mixtures for use in dry powder inhalers.
AB  - The physicochemical and aerodynamic properties of spray dried powders of the
      drug/drug mixture salbutamol sulphate/ipratropium bromide were investigated. The
      in vitro deposition properties of spray dried salbutamol sulphate and the spray
      dried drug/excipient mixtures salbutamol sulphate/lactose and salbutamol
      sulphate/PEG were also determined. Spray drying ipratropium bromide monohydrate
      resulted in a crystalline material from both aqueous and ethanolic solution. The
      product spray dried from aqueous solution consisted mainly of ipratropium bromide
      anhydrous. There was evidence of the presence of another polymorphic form of
      ipratropium bromide. When spray dried from ethanolic solution the physicochemical
      characterisation suggested the presence of an ipratropium bromide solvate with
      some anhydrous ipratropium bromide. Co-spray drying salbutamol sulphate with
      ipratropium bromide resulted in amorphous composites, regardless of solvent used.
      Particles were spherical and of a size suitable for inhalation. Twin impinger
      studies showed an increase in the fine particle fraction (FPF) of spray dried
      salbutamol sulphate compared to micronised salbutamol sulphate. Co-spray dried
      salbutamol sulphate:ipratropium bromide 10:1 and 5:1 systems also showed an
      increase in FPF compared to micronised salbutamol sulphate. Most co-spray dried
      salbutamol sulphate/excipient systems investigated demonstrated FPFs greater than
      that of micronised drug alone. The exceptions to this were systems containing PEG
      4000 20% or PEG 20,000 40% both of which had FPFs not significantly different
      from micronised salbutamol sulphate. These two systems were crystalline unlike
      most of the other spray dried composites examined which were amorphous in nature.

PMID- 16815655
TI  - A new copolymer membrane controlling clonidine linear release in a transdermal
      drug delivery system.
AB  - A new type of copolymer membranes was prepared through photosynthesis of mixtures
      of three different monomers. The membranes present a linear permeation property
      in clonidine transdermal drug delivery system. Monomers used in the
      photosynthesis were 2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate
      and sec-butyl tiglate. Permeation property of the membranes with different
      monomer ratios and thickness were investigated. When clonidine concentrations
      were in 3.0 - 5.0 mg/ml range, membranes showed near zero order permeation rates.
      An optimized membrane was characterized by FTIR, DSC and SEM.

PMID- 16815656
TI  - In vitro and in vivo evaluation of floating riboflavin pellets developed using
      the melt pelletization process.
AB  - Floating pellets were prepared using the melt pelletization process in a Mi-Pro
      high shear mixer (Pro-C-epT, Belgium). Formulations were based on a mixture of
      Compritol and Precirol as meltable binders and on the use of sodium bicarbonate
      and tartaric acid as gas-generating agents. Good floating abilities were obtained
      by using the gas-generating agents in both the inner matrix and the outer coating
      layer of the pellets. In vitro evaluation of floating capability was performed
      both by using the resultant weight apparatus and by counting floating pellets at
      the surface of beakers containing 0.1N HCl solution, in vivo evaluation of
      floating pellets capabilities was also performed. Riboflavin-containing floating
      pellets (FRF) were administered orally to nine healthy volunteers versus non
      floating pellets (NFRF). Volunteers were divided in two groups, fasted group
      (n=4) 729 kcal and fed group (n=5) 1634 kcal as the total calorie intake on the
      testing day. An increase of urinary excretion of riboflavin was observed when the
      volunteers were dosed with the floating pellets, especially after feeding. As
      riboflavin has a narrow window of absorption in the upper part of small
      intestine, this phenomenon could be attributable to the gastric retention of
      floating pellets.

PMID- 16815657
TI  - PLA-microparticles formulated by means a thermoreversible gel able to modify
      protein encapsulation and release without being co-encapsulated.
AB  - The aim of this work was to develop a novel strategy for the formulation of
      biodegradable PLA microspheres as delivery systems for proteins or peptides. The
      strategy is based on the exploitation of the gel-sol transition of the
      thermoreversible Pluronic F127 gel. The gel allows the formation of the particles
      without be co-entrapped in the matrix. The microspheres prepared using the novel
      technique (TG-Ms, or thermoreversible gel-method microspheres) were characterized
      in vitro (as concerns the size, the morphology, the protein encapsulation, the
      release and the protein distribution in the polymer matrix), in comparison with
      microspheres prepared using the classical double emulsion/solvent evaporation
      method (w/o/w-Ms). Two types of bovine serum albumin (BSA), with different water
      solubility, were used as model proteins. TG-Ms exhibited small size (7-50 m) and
      high protein content (8.6%, w/w) regardless of the BSA water solubility, in
      contrast with w/o/w-Ms, which revealed a size range of 100-130 microm and a
      protein content related to the BSA water solubility. TG-Ms, in spite of their
      smaller size respect of the w/o/w-Ms, displayed a reduced initial burst effect
      and a higher rate in the second release phase that resulted in a quasi-constant
      profile. The release behavior of the TG-Ms may be attributable to both the
      localization of the protein in the particle core, as shown by the confocal laser
      scanning microscopy analysis on labeled-BSA loaded microspheres, and the few
      pores in the matrix, as shown by the scanning electron microscopy. A working
      hypothesis about the mechanism of the particle formation was also discussed.

PMID- 16815658
TI  - Some toxicological studies of Momordica charantia L. on albino rats in normal and
      alloxan diabetic rats.
AB  - Momordica charantia L. (MC) (Cucurbitaceae) commonly known as balsam pear, bitter
      gourd or karela, used in several purposes in traditional medicine is an important
      medicinal plant. Two sets of experiments were carried out, the first experiment
      indicated that the LD(50) for MC juice and alcoholic extracts were 91.9 and
      362.34 mg/100g b.wt., respectively, of subcutaneously "s.c." injected mice. The
      toxic signs were recorded within the first 24 h post-injection. The second
      experiment was performed to evaluate the effect of MC juice and alcoholic
      extracts on blood glucose and other biochemical parameters in normal and diabetic
      rats. Both extracts induced a significant decrease in serum glucose levels in
      normal and diabetic rats. The two extracts did not show any significant effect in
      urea, creatinine, ALT, AST and AP in normal rat, while in diabetic rats the two
      extracts caused a significant decrease in serum urea, creatinine, ALT, AST, AP,
      cholesterol and triglyceride levels. Also, these results suggested that MC
      extracts possesses anti-diabetic, hepato-renal protective and hypolipidemic
      effect in alloxan-induced diabetic rats. Thus, MC is alternative therapy that has
      primarily been used for lowering blood glucose levels in patients with diabetes
      mellitus.

PMID- 16815659
TI  - Adaptogenic activity of Caesalpinia bonduc seed extracts in rats.
AB  - Caesalpinia bonduc Roxb. (Caesalpiniaceae) seed extracts were screened for
      adaptogenic activity using cold stress model and swim endurance model, the seed
      coat as well as kernel extracts showed significant antistress activity when
      administered orally at a dose of 300 mg/kg. The extracts significantly increased
      the swim endurance time. Stress induced animals exhibited hypoglycaemia as well
      as depletion in serum cortisol level and increased total leukocyte count, the
      extracts showed a significant action in overcoming these imbalances. It was also
      found that extracts proved efficient in controlling the hyperlipidaemic condition
      due to stress.

PMID- 16815660
TI  - Submandibular sialogram performed through a Wharton's duct fistula: technical
      adaptation of conventional technique.
AB  - We report a case of submandibular duct fistula in which a sialogram was performed
      through the fistulous opening after attempt of sialography through the Wharton's
      duct had failed. To our knowledge, this technical modification in obtaining a
      sialogram has not been described previously in scientific literature. Blunt
      tipped needles and polythene catheters are commonly used for cannulation of the
      submandibular duct orifice for obtaining a sialogram. However, in this case, a
      larger gauge metallic cannula was employed to opacify the ductal system through
      the fistula.

PMID- 16815661
TI  - MR imaging of cerebral malaria in a child.

PMID- 16815662
TI  - High performance liquid chromatographic analysis of MS23 piperidine analog MSP001
      in rat plasma.
AB  - MSP001 is a newly synthesized piperidine analog of the lead antihypertensive
      compound MS23 that dually targets cAMP-specific type 4 phosphodiesterase and L
      type calcium channels. We validated an analytical protocol for MSP001 in rat
      plasma using high performance liquid chromatographic method. A C18 column and a
      phosphate/acetonitrile buffer were used to perform the chromatographic
      separation. UV detection was carried out at 307 nm, a wavelength at which an
      absorption peak was detected for this group of compounds. The calibration curve
      for MSP001 was linear in the range from 25 to 10,000 ng/ml. The limit of
      quantification (LOQ) was 25 ng/ml. The results demonstrate that this method has
      high linearity (R=0.99995), compound specificity, and acceptable
      precision/accuracy. The protocol is suitable for in vivo pharmacokinetic studies
      on the compound.

PMID- 16815663
TI  - Salvage radical prostatectomy for radiorecurrent prostate cancer: indications and
      results.
AB  - AIMS: A rise in the incidence of radiorecurrent prostate cancer is to be
      expected, since approximately one third of early prostate cancer cases are
      nowadays treated with a radiotherapy modality. One possibility in treating
      radiorecurrent prostate cancer is salvage prostatectomy. Our objective was to
      look into our own experience with salvage radical prostatectomy and to analyse
      outcome and morbidity. METHODS: A computer search through our hospital database
      identified 11 patients who underwent a salvage radical prostatectomy for
      radiorecurrent cancer over the last 15 years. All data were retrospectively
      analysed and confronted with the literature. RESULTS: Although the surgery was
      mostly difficult, there were no intraoperative complications. Bladder neck
      stricture is the most common postoperative complication (18%). Continence rates
      are worse than in classical radical prostatectomy. All patients lost potency,
      since no attempt was made to spare the neurovascular bundles. With a mean follow
      up of 6.9 years, biochemical disease-free survival rates was 55%, while overall
      and cancer-specific survival was 91%. CONCLUSION: While most patients with
      radiorecurrent prostate cancer will be treated by many experts with hormonal
      therapy, a salvage radical prostatectomy can give a second chance for cure in
      carefully selected patients.

PMID- 16815664
TI  - Epidural blood patch for the treatment of post-dural puncture headache in
      pregnant women: never too early, never too late!

PMID- 16815665
TI  - [Monitoring of cerebral oxygenation with SvjO(2) or PtiO(2)].
AB  - Jugular venous oxygen saturation (SvjO(2)) monitoring has been developed in order
      to detect cerebral ischaemia. The interpretation of SvjO(2) values remains
      nevertheless complex, and should be associated with cerebral haemodynamic
      multimonitoring with ICP and transcranial Doppler. With the hypothesis of a
      constant cerebral oxygen consummation, and also with a constant haematocrit,
      SvjO(2) variations correlates with cerebral blood flow variations. After a brain
      trauma, an SvjO(2)<50% or>75% is associated with a bad prognosis. To maintain
      SvjO(2)>50% constitutes a reasonable therapeutic objective, but the benefice
      associated with such a strategy has not been validated. Oxygen partial pressure
      (PtiO(2)) in the brain parenchyma may be monitored in the non-lesioned area
      (usually frontal) in order to detect a global cerebral ischaemia, or in the
      penumbra of a cerebral lesion in order to detect a local ischaemia. The values
      associated with an ischemic risk are not fully defined and may be under 10-15
      mmHg. A concomitant metabolic monitoring by cerebral microdialysis is of
      importance to fully address the real cerebral local ischaemic burden. Scientific
      studies are mainly focused on patients with a brain traumatism. Nor SvjO(2), nor
      PtiO(2) monitoring have at present been demonstrated to be associated with a
      clinical benefit, and their use should be restricted to scientific research.

PMID- 16815666
TI  - [Noninvasive ventilation and acute severe asthma].

PMID- 16815667
TI  - Anti-angiogenic and anti-HER therapy.
AB  - The recent completion of the human genome sequence provided the basis and the
      tools to better understand the cellular biological complexity in both healthy and
      disease conditions, such as human cancer. In recent years, the improvement in
      biological and molecular knowledge enabled us to identify new targets and
      innovative drugs, allowing the beginning of new therapeutic strategies based on
      the so called "target oriented therapies".

PMID- 16815668
TI  - Sensitive domains of self-concept in obsessive-compulsive disorder (OCD): further
      evidence for a multidimensional model of OCD.
AB  - Aspects of self-concept have been implicated in recent empirical and theoretical
      investigations of obsessive-compulsive disorder (OCD). This article extends
      previous theory and research by investigating the proposal that specific self
      structures may be linked with OCD [e.g., Doron, G., & Kyrios, M. (2005).
      Obsessive-compulsive disorder: a review of possible specific internal
      representations within a broader cognitive theory. Clinical Psychology Review,
      25, 415-432]. In particular, it was hypothesized that individuals who value the
      domains of morality, job and scholastic competence, and social acceptability, but
      who feel incompetent in these domains (i.e., "sensitive" domains of self), would
      hold a greater level of OC-related beliefs and display more OC-symptoms. The
      study was performed in 198 non-clinical participants, using a multidimensional
      measure of self-concept. As predicted, it was found that sensitivity in the four
      domains was related to higher levels of OC-related beliefs. Sensitivity in the
      domains of morality, job competence and social acceptability also related to
      higher levels of OC-symptoms. Further, these findings were generally maintained
      when controlling for global self-worth. Based on these results, it is argued that
      sensitivity of self-concept may be associated with OC cognitions and phenomena.
      Implications for theory and treatment are discussed.

PMID- 16815669
TI  - Are congenital anorectal malformations more frequent in newborns conceived with
      assisted reproductive techniques?
AB  - One of the major concerns about ART is the risk of birth defects in children born
      after in vitro fertilization. We report on a cohort of consecutive children
      affected with anorectal malformation (ARM) requiring surgical correction in which
      we found a significantly high proportion (Odds ratio 13.31, 95% confidence limits
      4.0-39.6) of children born after ART. Our data is in agreement with the result of
      a recent epidemiological study in Sweden. Further studies are necessary to define
      the risk and identify the causes, if any. At present, couples undergoing ART
      should be informed of the general risk of congenital anomalies, of which, ARM can
      be suggested as an example.

PMID- 16815670
TI  - Voice-related Quality of Life in laryngectomees: assessment using the VHI and V
      RQOL symptom scales.
AB  - The primary purpose of this study was to investigate the effect of the voice
      impairment across the physical, emotional, and functional domains in patients
      using valved speech following total laryngectomy with the help of two symptom
      specific scales. The study design used was a cross-sectional cohort. The setting
      was the Head and Neck Oncology Unit of a tertiary referral centre. Subjects were
      54 patients who had undergone total laryngectomy. Two voice-specific
      questionnaires, the Voice-Related Quality of Life (V-RQOL-short form) Measure,
      and the Voice Handicap Index (VHI-long form) were used. The main outcome measure
      was patient perception of the voice following total laryngectomy in response to
      specific questions correlated with sociodemographic/treatment factors. Responses
      were received from 40 males and 14 females (response rate of 85.7%) with a median
      age of 63.4 years (range: 37-84). The V-RQOL overall analysis showed that 3
      patients (5.6%) scored "excellent," 29 patients (53.7%) "fair to good," 14
      patients (25.9%) "poor to fair," and 8 patients (14.8%) "poor." Analysis of the
      VHI revealed that 20 patients (37.0%) had a minimal handicap, 20 patients (37.0%)
      a moderate handicap, and 14 patients (25.9%) had a serious voice handicap. The
      individual domain or subscale scores for the VHI revealed a mean (SD) functional
      score of 15.8 (7.7), a physical score of 13.6 (7.2), and finally an emotional
      score of 11.6 (8.9). Functional aspects of the voice were significantly affected
      by age, radiotherapy, and chemotherapy (Spearman rho, P=0.01; Mann-Whitney,
      P=0.04 and P=0.01). The physical aspects of the voice were significantly affected
      by age and chemotherapy (Spearman rho, P=0.004; Mann-Whitney, P=0.04). Only age
      significantly affected the emotional aspects of the voice (Spearman rho,
      P=0.002). We found a strong correlation (Spearman rho, P<0.001) between the V
      RQOL and VHI questionnaires. Our study revealed that the V-RQOL and VHI scores in
      our series of patients following voice restoration in laryngectomees were
      consistent with that reported in the literature. Only age, radiation, and
      chemotherapy were seen to influence the voice handicap scores. In addition, both
      symptom scales had good correlation between them and either one could be used
      with reliability in laryngectomees with a few modifications.

PMID- 16815671
TI  - Objective and subjective evaluation of voice quality in multiple sclerosis.
AB  - The aim of this comparative, controlled, cross-sectional study is to evaluate the
      voice quality in patients with multiple sclerosis (MS) by subjective and
      objective methods. Female patients with MS (n=27) and age- and sex-matched
      healthy controls (n=27) were included in this study. Vocal functions were
      evaluated by a multidimensional set composed of videolaryngostroboscopic
      examination, acoustic analysis, and subjective measurements (GRBAS and "Voice
      Handicap Index"). Jitter percent, shimmer percent, and soft phonation index (SPI)
      values were higher in MS patients compared to controls (Jitt, P=0.001; Shim,
      P=0.033; SPI P<0.0001). Maximum phonation time was significantly shorter for MS
      patients compared to controls (P<0.0001). Stroboscopic examination revealed that
      16 out of 27 MS patients have a "posterior chink" as glottic closure pattern with
      higher SPI values (40%). Noise to harmonic ratio (NHR) and mean fundamental
      frequency (F0) values were similar for MS and control groups (NHR, P=0.737; F0,
      P=0.976). In this study, most of the MS patients had dysphonia due to weakness of
      voice. MS tends to worsen acoustic parameters including fundamental frequency,
      SPI, and jitter values. These results are consistent with the more asthenic voice
      quality observed in MS group.

PMID- 16815672
TI  - Unfolding preprocessing for meaningful time series clustering.
AB  - Clustering methods are commonly applied to time series, either as a preprocessing
      stage for other methods or in their own right. In this paper it is explained why
      time series clustering may sometimes be considered as meaningless. This
      problematic situation is illustrated for various raw time series. The unfolding
      preprocessing methodology is then introduced. The usefulness of unfolding
      preprocessing is illustrated for various time series. The experimental results
      show the meaningfulness of the clustering when applied on adequately unfolded
      time series.

PMID- 16815673
TI  - Fuzzy classification by fuzzy labeled neural gas.
AB  - We extend the neural gas for supervised fuzzy classification. In this way we are
      able to learn crisp as well as fuzzy clustering, given labeled data. Based on the
      neural gas cost function, we propose three different ways to incorporate the
      additional class information into the learning algorithm. We demonstrate the
      effect on the location of the prototypes and the classification accuracy.
      Further, we show that relevance learning can be easily included.

PMID- 16815674
TI  - Surviving cell death through epidermal growth factor (EGF) signal transduction
      pathways: implications for cancer therapy.
AB  - There is a balance between cell death and survival in living organisms. The
      ability of cells to sense their environment and decide to survive or die is
      dependent largely upon growth factors. Epidermal growth factor (EGF) is a key
      growth factor regulating cell survival. Through its binding to cell surface
      receptors, EGF activates an extensive network of signal transduction pathways
      that include activation of the PI3K/AKT, RAS/ERK and JAK/STAT pathways. These
      pathways predominantly lead to activation or inhibition of transcription factors
      that regulate expression of both pro- and anti-apoptotic proteins effectively
      blocking the apoptotic pathway. In cancer, EGF signaling pathways are often
      dysfunctional and targeted therapies that block EGF signaling have been
      successful in treating cancers. In this review, we will discuss the EGF survival
      signaling network, how it cross-talks with the apoptotic signaling pathways and
      the therapeutic drugs targeting the EGF survival pathway used to treat cancers.

PMID- 16815675
TI  - P2X7 and phospholipid signalling: the search of the "missing link" in epithelial
      cells.
AB  - The purinergic receptor P2X(7) is widely expressed in epithelial cells. This
      receptor shares in common with the other P2X receptors the ability to form a non
      selective cation channel. On the other hand, the COOH terminus of P2X(7) seems to
      allow this receptor to couple to a spectrum of downstream effectors responsible
      for the regulation of cell death and pore formation among other functions.
      However, the coupling of P2X(7) to these downstream effectors, as well as the
      identity of possible adapters directly interacting with the receptor, remains
      poorly understood. Here we review the ability of P2X(7) to activate phospholipid
      signalling pathways in epithelial cells and propose this step as a possible link
      between the receptor and other downstream effectors. The P2X(7) ability to
      control the cellular levels of several lipid messengers (PA, AA, DAG, ceramide,
      etc.) through the modulation of phospholipases (C, A(2), D) and neutral
      sphingomyelinase is described. These pathways are sometimes regulated
      independently of the channel function of the receptor. Recent data concerning
      P2X(7) localization in lipid rafts is also discussed in relation to the coupling
      to these pathways and dissociation from channel function.

PMID- 16815676
TI  - Effects of hesperetin on vessel structure formation in mouse embryonic stem (mES)
      cells.
AB  - OBJECTIVE: The present study investigated the effects of hesperetin on vessel
      structure formation in mouse embryonic stem (mES) cells with regard to whether
      hesperetin acts as an antioxidant or pro-oxidant. Some flavonoids enhance
      antioxidant systems while increasing oxidative stress in the body. METHODS: After
      their differentiation into endothelial-like cells for 10 d, mES cells were
      treated with 1 to 100 muM of hesperetin for 24 h. RESULTS: Hesperetin efficiently
      inhibited the formation of vessel-like tubular structures consisting of platelet
      endothelial cell adhesion molecule-1-immunoreactive cells and significantly (P <
      0.05) increased the generation of reactive oxygen species in a concentration
      dependent manner. Although glutathione (in its reduced and oxidized forms) in mES
      cells was not affected by hesperetin, the 8-iso-prostaglandin F2(alpha) content
      was decreased. In addition, cytotoxicity-induced hesperetin was not found;
      lactate dehydrogenase release and cell viability were determined as an index of
      cell damage. CONCLUSION: Taken together, the present study shows that hesperetin
      inhibits vessel formation by pro-oxidant means and suggests its potential as an
      antiangiogenic agent.

PMID- 16815677
TI  - A population-based survey of childhood epilepsy in Okayama Prefecture, Japan:
      reclassification by a newly proposed diagnostic scheme of epilepsies in 2001.
AB  - The purpose of this study is to clarify the usefulness and problems of the newly
      proposed classification of epilepsies (International League Against Epilepsy:
      ILAE, 2001) in the epidemiological studies of epilepsy. We previously conducted
      an epidemiological study in Okayama Prefecture, Japan, in 1999, using the ILAE
      1989 classification. Among 250,997 children under 13 years of age, 2220 epileptic
      patients were ascertained. In this study, we reclassified them according to the
      ILAE 2001 classification, focusing on axes 2 (seizure types) and 3 (syndromes).
      We were able to classify 1803 (95.0%) seizure types out of 1899 with detailed
      clinical information. In focal seizures, the most common were secondarily
      generalized seizures (88.6%), which generally do not represent a unique anatomic
      substrate. In generalized seizures, topic-clonic seizures (40.7%) and spasms
      (21.0%) were the most common. We identified only 269 (12.1%) patients with
      specific epilepsy syndromes out of the 2220. We classified 1761 patients without
      specific syndromic diagnoses only by axis 2, but the new concept of epileptic
      seizure types, representing a unique pathophysiologic mechanism and anatomic
      substrate, was not very meaningful in most cases, even in those with focal
      seizures.

PMID- 16815678
TI  - Epilepsy syndromes undetermined whether focal or generalized in infants.
AB  - PURPOSE: To describe the seizures in infants with epilepsy syndromes undetermined
      whether focal or generalized. METHODS: This was a retrospective video-EEG study
      of seizures recorded at Children's Memorial Hospital (CMH), Chicago, IL, in
      infants diagnosed with epilepsy syndromes undetermined whether focal or
      generalized. RESULTS: Of 69 infants with seizures recorded, 23 (33%) had
      epilepsies undetermined whether focal or generalized with both generalized and
      focal seizures, 17 of which (25% of the total) had epilepsies with both focal and
      generalized seizures not further specified. The predominant seizure type was
      spasms with focal seizures. CONCLUSIONS: We propose several small modifications
      to the existing 1989 ILAE epilepsy syndrome classification: epilepsies with both
      focal and generalized seizures could be re-labeled "pleomorphic epilepsies" for
      simplicity and should include idiopathic and symptomatic subgroups. We believe
      these epilepsies are not uncommon in the group of infants with intractable
      seizures and may have yet to be discovered metabolic and genetic determinants.

PMID- 16815679
TI  - Paradoxical urinary phenytoin metabolite (S)/(R) ratios in CYP2C19*1/*2 patients.
AB  - Phenytoin (PHT) is primarily metabolized to 5-(4'-hydroxyphenyl)-5
      phenylhydantoin (p-HPPH), accounting for 67-88% of an administered dose in
      humans. p-HPPH is formed by the cytochrome (CYP) 450 enzymes CYP2C9 and CYP2C19,
      then glucuronidated and excreted into the urine. CYP2C9 catalyses the prochiral
      formation of (R) and (S)-p-HPPH, and is approximately 40 times more
      stereoselective towards the formation of the (S) isomer whereas CYP2C19 is not
      stereoselective. Because of differential stereoselectivity, polymorphisms in the
      genes can alter the (S)/(R)-p-HPPH ratios. Genotyping for CYP2C9 and CYP2C19 was
      accomplished by a Taqman based assay. Twelve and twenty-four hour urine samples
      were collected from 45 epilepsy patients taking PHT under steady-state conditions
      and (S)/(R) ratios of p-HPPH were determined by chiral HPLC separation. The mean
      urinary (S)/(R) ratio in the 12-24h urine collection in subjects homozygous for
      CYP2C9*1/*1, CYP2C19*1/*1 was 24.2+/-3.1(n=21), whereas ratios in CYP2C9*1/*2 and
      CYP2C9*1/*3 subjects, were 11.1+/-3.3(n=7) and 2.7+/-0.6(n=2), respectively. One
      CYP2C9*2/*3 patient had a ratio of 2.1. Unexpectedly, CYP2C9*1/*1, CYP2C19*1/*2
      subjects had a mean (S)/(R) ratio as low as 12.9+/-1.7(n=12). Our results are
      generally consistent with single dose PHT studies. However, the (S)/(R)-p-HPPH
      ratios for the CYP2C9*1/*1, CYP2C19*1/*2 subjects, expected to be in the range of
      30-40, were only 12.9, suggesting some undetected linkage disequilibrium between
      CYP2C9 and CYP2C19 genes that could affect PHT elimination. Furthermore, our
      study suggests that measurement of urine ratios cannot be used as a marker for
      genotype determination.

PMID- 16815680
TI  - Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy
      models.
AB  - Cooling has been shown to terminate experimentally induced epileptiform activity
      in models of epilepsy without causing injury to the cooled brain, suggesting that
      cooling could represent an approach to seizure control in intractable focal
      epilepsies. Here we sought to determine the most effective way to apply cooling
      to abort spontaneous epileptiform discharges in in vitro brain slice models. We
      induced spontaneous epileptiform activity in rat brain slices by exposure to 4
      aminopyridine (4-AP), 4-AP plus bicuculline, and Mg(2+)-free artificial CSF
      (aCSF) at 28-34 degrees C. Extracellular field recordings were made at
      hippocampal or neocortical sites. Slice temperature was reduced by perfusion with
      cold aCSF. Rapid cooling at rates of 2-5 degrees C/s was compared to cooling at
      slower rates of 0.1-1 degrees C/s. Cooling at both rates reversibly aborted
      epileptiform discharges in all three models and at all recording sites. With
      rapid cooling, small temperature drops were highly effective in terminating
      discharges, an effect that was sustained for as long as the reduced temperature
      level was maintained. In contrast, slow cooling required much larger temperature
      drops to inhibit discharges. With slow cooling, absolute temperature drops to 21
      22 degrees C caused a 90% reduction in event frequency, but cooling to 14-15
      degrees C was required to terminate discharges. We conclude that rapid cooling as
      effectively aborts discharges in in vitro epilepsy models as does slow cooling,
      but the magnitude of the temperature change required is less. Practical devices
      to inhibit seizure activity may only need to induce small temperature drops, if
      the cooling can be applied sufficiently rapidly.

PMID- 16815681
TI  - Diagnostic issues and treatment of cryptogenic or symptomatic generalized
      epilepsies.
AB  - To clarify the diagnostic issues and treatment of patients with cryptogenic or
      symptomatic generalized epilepsies, not including West syndrome (WS), we
      investigated electroclinical change during the clinical course, and treatment
      effects in these patients. The selection criteria were minor generalized seizures
      as their main seizure type and diffuse epileptic discharges as their main EEG
      findings. Regarding EEG, we included EEGs that predominantly displayed multifocal
      spike-waves because of the inclusion of severe epilepsy with multiple independent
      spike foci (SE-MISF). We divided the subjects into two groups according to their
      main seizure types: Group A (54 patients) with brief tonic seizures and Group B
      (24 patients) with myoclonic seizures and/or atypical absences. The main
      epileptic syndromes were considered to be Lennox-Gastaut syndrome and SE-MISF in
      Group A, and epilepsy with myoclonic-astatic seizures in Group B. A history of WS
      was often seen in Group A, but it was exceptional in Group B. During the clinical
      course, seizure types did not basically change in Group A. EEG patterns were
      changeable in both groups. Although there was some overlap in electroclinical
      manifestations among epileptic syndromes, a transition between the two groups was
      not seen. High-dose valproate and ethosuximide were the most effective in Groups
      A and B, respectively. Long-term prognosis was significantly more favorable in
      Group B than in Group A.

PMID- 16815682
TI  - Concepts in classification and their relevance to epilepsy.
AB  - The classification of the epilepsies was advanced in order to formalize efforts
      to identify coherent clinical entities and to develop a standardized set of
      diagnostic terminology for facilitating communication among workers in the field
      world-wide. The classification initially was, and still is today, based primarily
      on description and expert opinion. In the era of genomics, neuroimaging and
      tremendous technological and scientific advances in the neurosciences, it is time
      to introduce scientific principles and standards into the classification of the
      epilepsies. Phylogenetic systematics provides an initial model worth studying in
      this context. While the classification of species cannot be directly applied to
      the classification of epilepsy syndromes, three general points can be
      appreciated. (1) In evolutionary biology, there is an operationalized definition
      of the end point (a species). There is no such definition of a syndrome. (2)
      There are rules and criteria for the type of evidence and how it is evaluated to
      determine whether an entity does or does not represent a separate species. There
      are currently no such rules or criteria for epilepsy syndromes. (3) There is an
      underlying model (evolution) that generates the diversity among species. With the
      possible and only partial exception of the idiopathic generalized epilepsies,
      there are no models to explain the diversity among the epilepsies. Previously
      held beliefs and convictions must, in time, give way to dispassionate examination
      of testable scientific hypotheses examined with rigorously collected scientific
      evidence. Although current classification is in need of revision, it has also
      come into common use and has great practical utility. Any changes to its form and
      to the terminology of the classification must be made only after careful
      deliberation and broad consensus is reached. The change(s) should be based on
      agreed upon scientific criteria and processes. Any changes should represent major
      improvements and not merely incremental steps.

PMID- 16815683
TI  - Biodegradation of benzene and its derivatives by a psychrotolerant and moderately
      haloalkaliphilic Planococcus sp. strain ZD22.
AB  - The potential for biodegradation of aromatic hydrocarbons simultaneously at low
      temperatures and under saline and alkaline conditions is not well understood, but
      such biodegradation would be useful for remediation of polluted sites. A
      psychrotolerant, moderately haloalkaliphilic pure culture using benzene as a sole
      source of carbon and energy was isolated by selective enrichment from alkaline
      and saline soils in the vicinity of the Daqing oil field in China. An analysis of
      the 16S rDNA gene sequence and morphological and physiological characteristics
      showed that this strain is a member of the genus Planococcus, and it was
      designated as strain ZD22. Strain ZD22 could grow at temperatures between 2 and
      36 degrees C (pH 7.5-11) and salt concentrations from 0.5 to 25%. Its optimal
      conditions for biodegradation of benzene were 20 degrees C (pH 9.5) and 10% salt
      concentration. Strain ZD22 not only utilized benzene, toluene, ethylbenzene and o
      xylene, but also degraded chlorobenzene, bromobenzene, iodobenzene and
      fluorobenzene. The kinetic model of strain ZD22 for benzene was solved to obtain
      mumax=0.34 h-1, Ks=0.041 mM, n=1.21, Sm=10.2 mM. To our knowledge, this is the
      first report of biodegradation of benzene and its derivatives simultaneously
      under multiple extreme conditions.

PMID- 16815684
TI  - Characterization of hydrocarbonoclastic bacterial communities from mangrove
      sediments in Guanabara Bay, Brazil.
AB  - Hydrocarbonoclastic bacterial communities inhabiting mangrove sediments were
      characterized by combining molecular and culture-dependent approaches. Surface
      sediments were collected at two sampling sites in Guanabara Bay (Rio de Janeiro,
      Brazil) and used to inoculate in vitro enrichment cultures containing crude oil
      to obtain hydrocarbonoclastic bacterial consortia. In parallel, in situ mesocosms
      (located in the Guapimirim mangrove) were contaminated with petroleum. Comparison
      of bacterial community structures of the different incubations by T-RFLP analyses
      showed lower diversity for the enrichment cultures than for mesocosms. To further
      characterize the bacterial communities, bacterial strains were isolated in media
      containing hydrocarbon compounds. Analysis of 16S rRNA encoding sequences showed
      that the isolates were distributed within 12 distinct genera. Some of them were
      related to bacterial groups already known for their capacity to degrade
      hydrocarbons (such as Pseudomonas, Marinobacter, Alcanivorax, Microbulbifer,
      Sphingomonas, Micrococcus, Cellulomonas, Dietzia, and Gordonia groups). Other
      strains, with high capacity for degrading hydrocarbons (aliphatic or aromatic),
      were related to isolates from hydrothermal vents that have not been thus far
      detected in hydrocarbon-contaminated sites, nor described for their ability to
      grow or degrade petroleum hydrocarbons. Degradation studies showed the ability of
      Marinobacter, Alcanivorax and Sphingomonas isolates to degrade both PAH and
      alkane compounds. Our results point out the rich microbial diversity of the
      mangroves, whose potential for hydrocarbon degradation is promising for future
      studies on pollutant bioremediation.

PMID- 16815685
TI  - Characterization of IS1110-like sequences found in Mycobacterium species other
      than Mycobacterium avium.
AB  - During study of a polycyclic aromatic hydrocarbon-degrading gene cluster in
      Mycobacterium sp. SNP11, which is a fast-growing strain related to Mycobacterium
      gilvum, a DNA segment with very high similarities to the IS1110 element of
      Mycobacterium avium was identified. Insertion sequence IS1110 was discovered for
      the first time in 1994 during a study of plasmid incidence in AIDS-derived M.
      avium strains. This element had thus far been detected in most human, veterinary,
      and environmental M. avium isolates, but not in other Mycobacterium species such
      as M. bovis, M. tuberculosis, M. xenopi, M. kansasii or M. gordonae. In the
      present paper, we describe the isolation and characterization of ISMysp1, an
      IS1110-like element present in several copies in the genome of Mycobacterium sp.
      strain SNP11. PCR and hybridization experiments revealed that this element is
      commonly found in fast-growing Mycobacterium strains. Moreover, Blast searches
      against the recently sequenced genome of M. smegmatis mc(2)155 revealed that this
      strain contains four IS1110-like elements. Analysis and sequence comparison of
      the whole of the IS1110-like elements revealed several common features not found
      in the most closely related mycobacterial members, IS900, IS901, IS902, IS1626
      and IS1547.

PMID- 16815686
TI  - High-yield cultivation of Marinococcus M52 for production and recovery of
      hydroxyectoine.
AB  - Ectoine and hydroxyectoine, produced by Halomonas ssp. and Marinococcus ssp.,
      have been extensively characterized and proposed for biotechnological
      applications. Large-scale production of ectoine was achieved by implementing the
      so-called "milking process" by Bitop (Witten, Germany) and commercializing
      compatible solutes as stabilizers for biological systems. However, there is a
      continuing interest in optimization of the production process for hydroxyectoine
      alone, as the latter was shown to have greater stabilization capacity. Recently,
      Marinococcus strain M52 was selected for its ability to convert most ectoine into
      hydroxyectoine during a prolonged stationary phase. This study reports on the
      correlation between growth conditions and hydroxyectoine production in
      Marinococcus M52 cultivation. We demonstrated that a dissolved oxygen content
      higher than 10% during cultivation leads to more rapid accumulation of
      hydroxyectoine than of ectoine (with hydroxyectoine up to 1.6 g l-1). In
      addition, we employed a microfiltration bioprocess to improve biomass and yield
      of products (reaching 3.6 g l-1 of hydroxyectoine). Finally, we developed a novel
      extraction method based on osmotic down-shock coupled with thermal
      permeabilization to recover the desired products from the biomass.

PMID- 16815687
TI  - Study of danofloxacin depletion in eggs of laying hens after oral administration.
AB  - Danofloxacin was administered to 15 laying hens via drinking water for 12 days.
      Egg white and yolk from each egg were separated and danofloxacin residues were
      analysed by a high performance liquid chromatography method with fluorescence
      detection. Danofloxacin was detectable on the first day in egg white and on the
      second day in egg yolk after the beginning of administration, and higher
      danofloxacin residues accumulated in egg yolk than in egg white. Danofloxacin in
      egg white decreased fairly rapidly and was detectable up to 4 days after
      withdrawal of the drug. In egg yolk the residues declined slowly and were
      detectable up to 11 days after withdrawal of the drug.

PMID- 16815688
TI  - Efficacy of cefminox compared with amoxicillin/clavulanic acid as a single dose
      for the prevention of intra-abdominal sepsis in mice intraperitoneally infected
      with different strains of Escherichia coli and one strain of Bacteroides
      fragilis.

PMID- 16815689
TI  - Clinical efficacy of continuous infusion of piperacillin compared with
      intermittent dosing in septic critically ill patients.
AB  - Since the bactericidal effects of beta-lactam antibiotics are time dependent, the
      optimum strategy for their administration could be continuous infusion. In this
      prospective, randomised controlled trial to evaluate the clinical efficacy of
      continuous infusion therapy, we evaluated the outcomes for 40 septic critically
      ill patients who received piperacillin either continuously (2 g intravenously
      (i.v.) over 0.5 h as a loading dose followed by 8 g i.v. daily over 24 h (n=20))
      or as an intermittent infusion (3 g i.v. every 6h over 0.5 h (n=20)). Results
      from our study demonstrated that the clinical efficacy of piperacillin as a
      continuous infusion is superior to intermittent administration in critically ill
      patients. Change in APACHE II scores from baseline at the end of the second,
      third and fourth days, respectively, were 4.1, 5.1 and 5.2 for continuous
      infusion and 2.0, 2.6 and 2.8 for intermittent infusion (P< or =0.04).
      Considering minimum inhibitory concentrations (MICs) of 16 microg/mL and 32
      microg/mL, the percentage of time for which piperacillin plasma concentrations
      were higher than the MIC (%T>MIC) was calculated for each patient in the two
      groups. For MICs of 16 microg/mL and 32 microg/mL, %T>MIC in the continuous
      infusion group was 100% and 65% of the dosing interval, respectively; in the
      intermittent infusion group, %T>MIC was only 62% and 39% of the dosing interval.
      There was a significant relationship between clinical results and laboratory
      data. It was shown that the superiority of the clinical efficacy of continuous
      infusion could be related to piperacillin pharmacodynamics. Continuous infusion
      significantly reduced the severity of illness as demonstrated by APACHE II scores
      during therapy.

PMID- 16815690
TI  - In vitro activities of various piperacillin and sulbactam combinations against
      bacterial pathogens isolated from Intensive Care Units in Taiwan: SMART 2004
      programme data.
AB  - We investigated the in vitro activity of various piperacillin and sulbactam
      combinations against Gram-negative bacterial isolates from Intensive Care Units
      (ICUs) in Taiwan. Antimicrobial susceptibility testing of 1030 bacterial isolates
      recovered from ICUs of nine major teaching hospitals was performed using the agar
      dilution method. Sulbactam was added to piperacillin either at a fixed sulbactam
      concentration of 4 mg/L and 8 mg/L or at a piperacillin:sulbactam ratio of 2:1
      and 4:1. Piperacillin/sulbactam at a ratio of 2:1 or a fixed 8 mg/L concentration
      of sulbactam had better activities against Escherichia coli, Klebsiella
      pneumoniae, Proteus mirabilis and Serratia marcescens than other
      piperacillin/sulbactam formulations. For Pseudomonas aeruginosa,
      piperacillin/sulbactam (2:1 or 4:1 ratios) had MIC(90) values (minimum inhibitory
      concentration for 90% of the organisms) of 64 mg/L (>90% susceptibility) compared
      with 64 mg/L for cefoperazone/sulbactam (68% susceptibility) and 128 mg/L for
      piperacillin/tazobactam (82% susceptibility). For Acinetobacter baumannii, both
      piperacillin/sulbactam (either 2:1 ratio or a fixed 8 mg/L sulbactam) and
      cefoperazone/sulbactam were the most potent agents. Adding sulbactam to
      piperacillin resulted in increased susceptibility rates among piperacillin
      resistant P. aeruginosa (53-57% in either 2:1 or 4:1 ratios) and A. baumannii (38
      46% in either 2:1 ratio or a fixed 8 mg/L concentration of sulbactam) isolates.
      Results of susceptibility tests with piperacillin/sulbactam are dependent on the
      method used. Piperacillin/sulbactam combinations possessed better in vitro
      activities than piperacillin alone or piperacillin/tazobactam against P.
      aeruginosa and A. baumannii.

PMID- 16815691
TI  - Associations between COMTVal158Met polymorphism and cognition: direct or indirect
      effects?
AB  - BACKGROUND: Previous work suggests that reaction time variability (RTV) in
      attentional tasks, as a measure of cognitive stability, is associated with degree
      of Val loading in COMT Val(158)Met genotype, and that this association may be
      relevant for the aetiology of schizophrenia. This study examined (i) to what
      degree RTV pertaining to tasks of varying cognitive complexity would be
      associated with increased risk for schizophrenia and (ii) to what degree this
      would be mediated by Val loading. METHODS: COMT genotyping was investigated in a
      sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21
      controls. All participants performed the Flanker continuous performance test.
      RESULTS: Schizophrenia liability was associated with number of correct trials of
      the Flanker test, but not with RTV, and this association was not mediated by COMT
      Val(158)Met genotype. Similarly, Met loading was associated with number of
      correct trials and with RTV, but this was not mediated by schizophrenia
      liability. CONCLUSIONS: Associations between COMT Val(158)Met genotype and RTV do
      not appear to reflect transmission of schizophrenia liability in families.
      Differential associations with Val and Met alleles across studies suggest
      indirect effects through gene-gene interactions or the influence of a functional
      polymorphism near COMT Val(158)Met.

PMID- 16815692
TI  - Long-chain Acyl-CoA is not primarily increased in myotubes established from type
      2 diabetic subjects.
AB  - Accumulation of intramuscular long-chain acyl-CoA esters (LCACoA) has previously
      in animal and human models been suggested to play an important role in lipid
      induced insulin resistance. The aim of this study was to examine whether myotubes
      established from type 2 diabetic (T2D) subjects and lean controls express
      differences in long-chain acyl-CoA esters (LCACoA) precultured under
      physiological conditions and during chronic exposure to palmitate (PA) and oleic
      acids (OA) with/without acute insulin stimulation. No significant differences
      were found between diabetic and control myotubes, neither in the total amount nor
      among individual LCA-CoA species during basal and acute insulin stimulation. LCA
      CoA accumulated during exposure to palmitic acid but not during exposure to oleic
      acid. During PA and OA exposure, only palmitoyl-CoA, oleoyl-CoA and total LCA-CoA
      change. PA exposure increased the palmitoyl-CoA, whereas oleoyl-CoA was reduced
      and vice versa during OA exposure. No differences were found in the LCA-CoA level
      between T2D and control subjects, neither in the total amount nor in the
      individual specific LCA-CoA species during fatty acid exposure. Chronic (24 h),
      high PA, but not OA exposure induced insulin resistance at the level of glycogen
      synthesis in control subjects. These results indicate that (1) no primary defects
      are responsible for LCA-CoA accumulation in diabetic subjects; (2) LCA-CoA
      changes in vivo are partly adaptive to changes in the PA level and possibly other
      saturated fatty acids; and (3) PA induced insulin resistance may be mediated
      through an increased level of palmitoyl-CoA.

PMID- 16815693
TI  - Genetic polymorphisms of cytochrome P450 2B6 gene in Han Chinese.
AB  - Cytochrome P450 (CYP2B6) is an important enzyme that metabolizes more than eight
      compounds and about 3.0% of therapeutic drugs. The genetic polymorphisms of
      CYP2B6 have earlier been studied in Caucasian, Japanese and Korean, but the data
      are lacking for Han Chinese. The aim of this study was to investigate the
      frequencies of allelic variants of CYP2B6 in healthy Han Chinese and compare with
      those in other ethnic groups reported in the literature. Polymerase chain
      reaction (PCR)-restriction fragment length polymorphism (RFLP) method was used to
      test the five common non-synonymous single nucleotide polymorphisms (SNPs) of
      CYP2B6 gene, namely, 64C>T, 516G>T, 777C>A, 785A>G and 1459C>T in unrelated
      healthy Han Chinese (n=193). The study demonstrated that the frequencies of
      64C>T, 516G>T, 777C>A, 785A>G and 1459C>T SNPs in Han Chinese were 0.03, 0.21, 0,
      0.28 and 0.003, respectively. The frequencies of all five SNPs tested in female
      were higher than those in male, but the statistical difference was insignificant
      (P>0.05). Compared to the data reported in the literature, the frequencies of
      common CYP2B6 allelic variants in Chinese are similar to those of other Asian
      populations including Japanese and Korean, but markedly different from those in
      Caucasians. These results indicate the presence of marked ethnic difference in
      CYP2B6 SNP frequencies between Chinese and Caucasian. Further studies are
      required to explore the impact of these SNPs of CYP2B6 gene on the clinical
      response (efficacy and toxicity) to drugs that are substrates for CYP2B6 in
      patients.

PMID- 16815694
TI  - Biorelevant dissolution media as a predictive tool for glyburide a class II drug.
AB  - The purpose of this study was to predict the oral absorption of glyburide.
      Biorelevant dissolution methods, combined with permeability measurements and
      computational simulations, were used to predict the oral absorption of glyburide.
      The objective was to establish in vitro/in vivo correlations (IVIVCs) based on
      the biopharmaceutics drug classification system. The solubility of the glyburide
      powder was measured in different media. The dissolution behavior of two
      commercial tablet formulations was tested in different media. Two chemical grades
      of sodium taurocholate: low quality (LQ)=crude and high quality (HQ)=97% purity,
      and egg-lecithin: LQ=60% and HQ=99.1% purity were used to prepare fasted state
      small intestinal fluid (FaSSIF). Simulated intestinal fluid (SIF) and blank
      FaSSIF without lecithin and taurocholate (BL-FaSSIF) were used as controls. The
      dissolution tests were performed under constant pH and dynamic pH conditions. The
      dynamic pH range from 5.0 to 7.5 simulated the biological pH range of
      gastrointestinal (GI) tract in the fasted state. The drug permeability was
      studied using Caco-2 cell line. The predictions of the fraction dose absorbed
      were performed using GastroPlustrade mark. The results of the simulations were
      compared with actual clinical data taken from a bioequivalence study. The
      solubility of glyburide was highest in LQ-FaSSIF. The two tablet formulations had
      significantly different dissolution behaviors in LQ-FaSSIF. The in vitro data was
      used as the input function into a simulation software. The dynamic LQ-FaSSIF
      dissolution data achieved the best prediction of the average AUC and C(max) of
      the clinically observed data. The present study shows that BCS based parameters
      combined with software simulations can be used to establish an IVIVC for
      glyburide. In vitro/in silico tools can potentially be used as surrogate for
      bioequivalence studies.

PMID- 16815695
TI  - Genetic relatedness of a non-motile variant O157 enteropathogenic Escherichia
      coli (EPEC) strain and E. coli strains belonging to pathogenic related groups.
AB  - The study was undertaken to determine the clonal relationship and the genetic
      diversity among Escherichia coli isolates by comparing a non-motile O157 variant
      with three O157:H7 EHEC isolates and one O55:H7 enteropathogenic E. coli (EPEC)
      strain. E. coli strains were characterized by sorbitol phenotype, multilocus
      enzyme electrophoresis, pulsed-field gel electrophoresis, random amplification
      polymorphic DNA, and the presence of specific virulence genes (stx, E-hly and LEE
      genes). Sorbitol fermentation was observed in O157:H- (strain 116I), O55:H7 and
      O157:H7 (strain GC148) serotypes. stx1 or stx2 and E-hly genes were only detected
      among O157:H7 isolates. LEE typing revealed specific allele distribution:
      eaegamma, tirgamma, espAgamma, espBgamma associated with EPEC O55:H7 and EHEC
      O157:H7 strains (B1/1 and EDL 933), eaealpha, tiralpha, espAalpha, espBalpha
      related to the 116I O157:H- strain and the GC148 strain presented non-typable LEE
      sequences. Multilocus enzyme profiles revealed two main clusters associated with
      specific LEE pathotypes. E. coli strains were discriminated by random
      amplification of polymorphic DNA-polymerase chain reaction and pulsed-field gel
      electrophoresis methodologies. The molecular approaches used in this study
      allowed the determination of the genetic relatedness among E. coli strains as
      well as the detection of lineage specific group markers.

PMID- 16815696
TI  - Transcriptional regulation of the human alpha2(I) collagen gene (COL1A2), an
      informative model system to study fibrotic diseases.
AB  - During the past two decades, the human pro-alpha2(I) collagen gene (COL1A2) has
      emerged as an informative model in which to study the general principles that
      govern the transcriptional control of extracellular matrix deposition in normal
      and fibrotic conditions. Multiple studies have in fact delineated the genomic
      regions, cis-acting elements and trans-acting factors implicated in constitutive,
      cytokine-modulated and tissue-specific expression of COL1A2. These functional
      components are integrated into a regulatory network that consists of the proximal
      promoter, far-upstream enhancer and downstream repressor, and which operates
      according to two mechanisms. The first mechanism is one in which combinatorial
      interactions among promoter-bound proteins determine transcriptional outcome in
      different cellular and experimental contexts. The other mechanism is one whereby
      cooperative assembly of protein complexes at distantly located DNA elements
      directs spatiotemporal specificity. These transcriptional studies have also an
      additional value in translational research, in that they are providing the
      conceptual means to develop new animal models of and therapeutic strategies for
      fibrotic diseases.

PMID- 16815697
TI  - Role of COX-1 and COX-2 on skin PGs biosynthesis by mechanical scratching in
      mice.
AB  - We examined the involvement of cyclooxygenase (COX)-1 and COX-2 on mechanical
      scratching-induced prostaglandins (PGs) production in the skin of mice. The
      dorsal regions of mice were scratched using a stainless brush. COXs expressions
      in the skin were analyzed using real-time PCR and Western blotting. The effect of
      acetylsalicylic acid (ASA) on the ability of PGs production were determined based
      on skin PGs level induced by arachidonic acid (AA) application. Mechanical
      scratching increased PGD2, PGE2, PGI2 and PGF(2 alpha). COX-1 was constitutively
      expressed and COX-2 expression was enhanced by scratching. Intravenous
      administration of ASA inhibited PGs biosynthesis in the normal skin. PGs levels
      of the skin 6h after ASA administration (ASA 6 h) were almost equal to those of
      the skin 10 min after ASA administration (ASA 10 min). In the scratched skin, AA
      induced PGE2 and PGI2 of ASA 6 h were significantly higher than those of ASA 10
      min. The skin PGD2 and PGF(2 alpha) of ASA 10 min were almost same to those of
      ASA 6 h. In the normal skin of COX-1-deficient mice, skin PGD2 level was lower
      than that of wild-type mice, although PGE2, PGI2 and PGF(2 alpha) levels were
      almost equal to those of wild type. In the scratched skin of COX-1-deficient
      mice, PGD2, PGE2, PGI2 and PGF(2 alpha) levels were lower than those of wild-type
      mice. These results suggested that cutaneous PGD2 could be mainly produced by COX
      1, and PGE2 and PGI2 could be produced by COX-1 and COX-2, respectively, in mice.

PMID- 16815698
TI  - Potentiometric sensor for atrazine based on a molecular imprinted membrane.
AB  - A molecular imprinted polymer (MIP) membrane for atrazine, not containing
      macropores, was synthesized and implemented in a potentiometric sensor. It is
      expected to work like a solid ISE (where the specific carrier are the imprinted
      sites) the specific carrier being the imprinted site. The active ion is the
      protonated atrazine, positively charged. To form this species the determination
      is carried out in acidic solution at pH lower than 1.8, in which atrazine is
      prevalently monoprotonated. At these conditions the membrane potential increases
      with atrazine concentration over a wide concentration range (3 x 10(-5) to 1 x
      10(-3)M). The slope of the function E versus logc is about 25 mV/decade, showing
      that the atrazine form sorbed on MIP is the biprotonated one. The detection limit
      is determined by the relatively high concentration of atrazine released by the
      membrane in the sample solution at the considered conditions. It seems to be
      independent of the atrazine concentration in the internal solution of the sensor,
      but it depends on the acidity of the solution. The response time is less than 10s
      and the sensor can be used for more than 2 months without any divergence.

PMID- 16815699
TI  - Use of protoplasts from paired heterogenic bacterial species to detect tin
      contaminants: prospects for biosensor development.
AB  - Two different bacteria gave different respiratory responses to the test analytes,
      tributyl tin (TBT) and cadmium as expressed by positive sigmoid responses by
      Halomonas sp. (slope, +1.71 [TBT]; +1.76 [Cd]) and negative sigmoid responses by
      Bacillus pumilis (slope, -1.06 [TBT]; -0.59 [Cd]). The EC50 values determined
      from Hill plots for the response of Halomonas sp. to the TBT and Cd were 1 and
      8.5 mM, respectively, which were lower by a factor of 10 than the corresponding
      values for B. pumilis. With protoplasts of B. pumilis there was a major shift in
      the signal from sigmoid negative to positive with TBT (+1.35) but not Cd (-0.5),
      while the signals with the remaining protoplast-analyte combinations remained
      unchanged. For all four protoplast-analyte combinations the EC50 values were in
      the order of 10-100-fold lower than those for their whole cell counterparts. When
      other analytes were tested the protoplasts gave a similar response to tin as for
      TBT, but detected copper and 2,4-dichlorophenol with similar signal profiles to
      Cd and with lower sensitivity. The difference in signal and higher sensitivity of
      the two species protoplast system towards TBT/tin compared to the other analytes
      tested, suggests that it may feasible to develop this approach for the detection
      of tin residues.

PMID- 16815700
TI  - Membrane proteins shape up: understanding in vitro folding.
AB  - Progress in structural biology has begun to reveal the precise architecture of
      integral membrane proteins. However, the manner in which these complex structures
      are achieved remains unclear. Recent developments are starting to shed light on
      the unfolding and folding of a small but growing number of membrane proteins.
      Mechanistic details derived from kinetic and thermodynamic experiments now enable
      comparison of the folding of different membrane proteins and their water-soluble
      cousins. This work also has important implications for other structural and
      functional studies of membrane proteins in vitro.

PMID- 16815701
TI  - Molecular prognostic markers in resectable colorectal liver metastases: a
      systematic review.
AB  - BACKGROUND: Determination of prognosis in patients with resectable colorectal
      liver metastases (CLM) is desirable in order to improve case selection for
      surgery and tailor adjuvant treatment according to individual recurrence risk.
      Conventional clinicopathological factors lack the sensitivity to accurately
      achieve this goal. Consideration of tumour biology and the identification of
      molecular prognostic markers may allow more accurate risk stratification. METHOD:
      This systematic review examines evidence from published manuscripts looking at
      molecular markers in resectable colorectal liver metastases and their correlation
      with disease recurrence and survival following hepatectomy. RESULTS: Studies have
      yielded promising results in the search for prognostic molecular markers of CLM.
      Molecular biomarkers from varied aspects of tumour biology have been examined and
      a number of these, including proliferation indices, telomerase, thymidylate
      synthase, microvessel density and thrombospondin-1 appear to have prognostic
      utility in this context. Validation of other markers, notably p53, has been
      limited by a failure of methodologies to account for their biological complexity.
      CONCLUSIONS: A biomarker-based approach may yield significant benefits through
      informed treatment of resectable metastatic colorectal malignancy. Standardised
      retrospective analyses are necessary to confirm preliminary findings and identify
      existing and novel markers for inclusion into prospective studies. Assessment and
      verification of multiple molecular markers in this manner may allow molecular
      profiling of metastases and tailoring of therapy according to the biological
      aggressiveness of individual tumours. The advent of genomic- and proteomic-based
      technologies will allow the simultaneous analysis of multiple molecular markers
      and the derivation of disease profiles associated with disease recurrence and
      poor survival.

PMID- 16815702
TI  - Phase I and pharmacokinetic study of halofuginone, an oral quinazolinone
      derivative in patients with advanced solid tumours.
AB  - PURPOSE: Halofuginone (tempostatin) is a synthetic derivative of a quinazolinone
      alkaloid showing anti-angiogenic, anti-metastatic and anti-proliferative effects
      in preclinical studies. The objectives of this phase I study were to assess the
      dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD)
      and to study the pharmacokinetics (PKs) of halofuginone when administered once or
      twice daily orally to patients with advanced solid tumours. METHODS: Patients
      were treated with escalating doses of halofuginone at doses ranging from 0.5 to
      3.5 mg/day. For pharmacokinetic analysis plasma sampling was performed during the
      first and second course and assayed using a validated high-performance liquid
      chromatographic assay with mass spectrometric detection. RESULTS: Twenty-four
      patients received a total of 106 courses. The 'acute' MTD was reached at 3.5
      mg/day, with nausea, vomiting, and fatigue as DLT. The recommended dose for
      chronic administration was defined as 0.5mg/day with the requirement of 5HT3
      antagonists to control nausea and vomiting considered as DLT. Several patients
      experienced bleeding complications on treatment with halofuginone in which a
      causal relationship could not be excluded. The PKs of halofuginone were linear
      over the dose range studied with a large interpatient variability. CONCLUSIONS:
      In this study the DLT of halofuginone was nausea, vomiting, and fatigue. The
      recommended dose for phase II studies of halofuginone is 0.5mg administered
      orally, once daily.

PMID- 16815703
TI  - State of the art therapy in multiple myeloma and future perspectives.
AB  - Treatment for multiple myeloma (MM) has changed beyond recognition in the past
      decades. While until the early 1980s, MM caused a slow progressive decline in
      quality of life until death after about two years, today's patients can expect a
      50% chance of achieving a complete remission, a median survival time of five
      years and a 20% chance of surviving longer than ten years. State of the art
      therapy comprises: evidence-based supportive care; highly effective and well
      tolerated chemotherapeutic regimens; and for patients qualifying for intensive
      high-dose conditioning, autologous haematopoietic stem cell transplantation
      (HSCT) is an option. Maintenance therapy has become increasingly important since
      a majority of patients is able to achieve a good remission after front-line
      therapy which is aimed to be preserved as long as possible. In addition, improved
      understanding of the disease biology has led to the development of novel
      biological treatment agents, such as thalidomide, bortezomib and others, targeted
      at cellular mechanisms and interactions, e.g. with the bone marrow
      microenvironment. These strategies are incrementally integrated into modern MM
      care. This review considers recent clinical advancements in anti-myeloma
      strategies and provides an overview of the state of the art management of MM
      patients.

PMID- 16815704
TI  - The sirtuins hst3 and Hst4p preserve genome integrity by controlling histone h3
      lysine 56 deacetylation.
AB  - BACKGROUND: Acetylation of histone H3 lysine 56 (K56Ac) occurs transiently in
      newly synthesized H3 during passage through S phase and is removed in G2.
      However, the physiologic roles and effectors of K56Ac turnover are unknown.
      RESULTS: The sirtuins Hst3p and, to a lesser extent, Hst4p maintain low levels of
      K56Ac outside of S phase. In hst3 hst4 mutants, K56 hyperacetylation nears 100%.
      Residues corresponding to the nicotinamide binding pocket of Sir2p are essential
      for Hst3p function, and H3 K56 deacetylation is inhibited by nicotinamide in
      vivo. Rapid inactivation of Hst3/Hst4p prior to S phase elevates K56Ac to 50% in
      G2, suggesting that K56-acetylated nucleosomes are assembled genome-wide during
      replication. Inducible expression of Hst3p in G1 or G2 triggers deacetylation of
      mature chromatin. Cells lacking Hst3/Hst4p exhibit many phenotypes: spontaneous
      DNA damage, chromosome loss, thermosensitivity, and acute sensitivity to
      genotoxic agents. These phenotypes are suppressed by mutation of histone H3 K56
      into a nonacetylatable residue or by loss of K56Ac in cells lacking the histone
      chaperone Asf1. CONCLUSIONS: Our results underscore the critical importance of
      Hst3/Hst4p in controlling histone H3 K56Ac and thereby maintaining chromosome
      integrity.

PMID- 16815705
TI  - Plant signalling: the inexorable rise of auxin.
AB  - The flow of signalling molecules across a field of cells to generate a pattern
      that is then transduced into a differential response in those cells is a
      fundamental concept in developmental biology. Recent studies have identified a
      system that regulates the flux of the growth factor auxin through plant tissues
      via the subcellular asymmetric localization of specific transporters. The
      recurrent use of this auxin transport system in different developmental and
      physiological contexts reveals a fundamental mechanism underpinning
      organogenesis, stem cell positioning and the growth response of the plant to the
      environment. Here, I will discuss key advances in the identification of auxin
      transporters and their integration with auxin signal transduction pathways.

PMID- 16815706
TI  - 14-3-3 protein levels and isoform patterns in the cerebrospinal fluid of
      Creutzfeldt-Jakob disease patients in the progressive and terminal stages.
AB  - To elucidate the diagnostic value and to establish the 14-3-3 isoform patterns in
      the cerebrospinal fluid (CSF) of Creutzfeldt-Jakob disease (CJD) patients, we
      analysed the 14-3-3 isoform patterns in the CSF of 11 CJD patients using the
      Western immunoassay technique. 14-3-3 protein was detected in the CSF of seven
      CJD patients in the progressive stage, but not in four patients in the terminal
      stages whose brains were severely atrophied. The amount of 14-3-3 protein
      measured semi-quantitatively in the CSF was correlated with that of neuron
      specific enolase measured using an enzyme-linked immunosorbent assay in the same
      CSF. CJD patients showed five dominant 14-3-3 isoforms, gamma, epsilon, zeta, eta
      and beta, but 14-3-3 tau, which mainly originates from T lymphocytes, was not
      detected. 14-3-3 protein is released into the CSF as a consequence of the
      extensive and rapid destruction of the brain, and the presence of the five
      isoforms enhances the diagnostic value of 14-3-3 protein in the progressive
      stage.

PMID- 16815707
TI  - Decoding RNA motional codes.
AB  - When proteins and small molecules bind to RNA, they often alter its conformation.
      These structural changes are an essential aspect of the ability of RNA to sense
      signaling molecules and modulate gene expression. Thus far, few studies have been
      dedicated to understanding how RNA moves at a residue level and how these motions
      change upon complex formation. A recent report highlights how intrinsic motions
      in RNA correlate with its ability to bind to cognate ligands.

PMID- 16815708
TI  - Conformational toggle triggers a modulator of RNA polymerase activity.
AB  - Members of a recently discovered class of transcription factor, which includes
      the Gre factors that stimulate transcript cleavage, function by directly
      modulating the catalytic properties of RNA polymerase (RNAP). Now, three research
      groups have determined crystal structures of a Gre homolog, Gfh1, which inhibits
      all RNAP catalytic activities. Strikingly, these structures reveal a puzzling
      discrepancy between the Gfh1 and GreA conformations, but the discovery that a pH
      dependent conformational toggle alters Gfh1 activity suggests an elegant
      solution.

PMID- 16815709
TI  - Relative quantification in proteomics: new approaches for biochemistry.
AB  - Recent developments in mass spectrometry and protein arrays provide opportunities
      to derive systematically proteomic information from small samples of cellular
      material. Relative quantification among samples can be achieved with either gel
      based or gel-free approaches. Furthermore, the adaptation of specific techniques
      facilitates absolute quantification. Here, relative quantification in two
      dimensional gel electrophoresis is contrasted with that in non-gel-based
      approaches such as isobaric tagging of peptides, pre-labelling of living cells
      with isotopomeric forms of essential amino acids and protein array platforms. In
      addition, novel flow-cytometry-based approaches are considered. These
      technologies can all be used to determine accurately the levels of proteins or
      biomarkers in a wide range of samples.

PMID- 16815710
TI  - Protein disulfide isomerase: the structure of oxidative folding.
AB  - Cellular functions hinge on the ability of proteins to adopt their correct folds,
      and misfolded proteins can lead to disease. Here, we focus on the proteins that
      catalyze disulfide bond formation, a step in the oxidative folding pathway that
      takes place in specialized cellular compartments. In the endoplasmic reticulum of
      eukaryotes, disulfide formation is catalyzed by protein disulfide isomerase
      (PDI); by contrast, prokaryotes produce a family of disulfide bond (Dsb)
      proteins, which together achieve an equivalent outcome in the bacterial
      periplasm. The recent crystal structure of yeast PDI has increased our
      understanding of the function and mechanism of PDI. Comparison of the structure
      of yeast PDI with those of bacterial DsbC and DsbG reveals some similarities but
      also striking differences that suggest directions for future research aimed at
      unraveling the catalytic mechanism of disulfide bond formation in the cell.

PMID- 16815711
TI  - Manipulation of inflammation modulates hyperlipidemia in apolipoprotein E
      deficient mice: a possible role for interleukin-6.
AB  - There are increasing evidences showing that inflammation participates in
      atherosclerosis. Therefore, the therapeutic use of anti-inflammatory agents
      should be considered. We have induced chronic, aseptic inflammation upon the
      injection of turpentine and tested the effect of dexamethasone on lipoprotein
      metabolism and, consequently, atherosclerosis in apolipoprotein E-deficient mice.
      Aseptic inflammation caused a significant decrease in hyperlipidemia. Treatment
      with dexamethasone elicited the opposite effect increasing hyperlipidemia through
      mechanisms related to the increase in the synthesis of triglyceride-rich
      lipoproteins. Changes in plasma lipids correlated with those observed in the size
      of atherosclerotic lesions. Our data suggest the presence of a common mechanism
      present in both observations and which is probably related to the cytokine
      secretion. Among the candidates, we chose to test the effect of interleukin-6
      because it is involved in both processes, atherosclerosis and inflammation, and
      its expression is efficiently repressed by corticosteroids. The injection of
      recombinant interleukin-6 in our mice elicited the same effects observed in our
      model of inflammation. We conclude that manipulation of inflammation-related
      mechanisms modulates lipid homeostasis and development of atherosclerotic plaque
      in rodents.

PMID- 16815712
TI  - Direct and indirect effects of hedgehog pathway activation in the mammalian
      retina.
AB  - The morphogen Sonic hedgehog (Shh) is expressed by the projection neurons of the
      retina, retinal ganglion cells (RGCs) and promotes retinal precursor cell (RPC)
      proliferation. To distinguish between direct and indirect effects of Hedgehog
      (Hh) pathway activation in the perinatal mouse retina, we followed the fate of
      cells that expressed a constitutively active allele of Smoothened (SMO-M2), the
      signal transduction component of the Hh pathway. SMO-M2 expression promoted a
      cell-autonomous increase in CyclinD1 expression and RPC proliferation and
      promoted the development of cells with an inner nuclear layer identity. SMO-M2
      expression also inhibited rhodopsin expression in uninfected cells, thus
      highlighting an unexpected non-cell autonomous effect of Hh pathway activation on
      photoreceptor development.

PMID- 16815713
TI  - Fibertract segmentation in position orientation space from high angular
      resolution diffusion MRI.
AB  - In diffusion MRI, standard approaches for fibertract identification are based on
      algorithms that generate lines of coherent diffusion, currently known as
      tractography. A tract is then identified as a set of such lines selected on some
      criteria. In the present study, we investigate whether fibertract identification
      can be formulated as a segmentation task that recognizes a fibertract as a region
      where diffusion is intense and coherent. Indeed, we show that it is possible to
      segment efficiently well-known fibertracts with classical image processing
      methods provided that the problem is formulated in a five-dimensional space of
      position and orientation. As an example, we choose to adapt to this newly defined
      high-dimensional non-Euclidean space, called position orientation space, an
      algorithm based on the hidden Markov random field framework. Structures such as
      the cerebellar peduncles, corticospinal tract, association bundles can be
      identified and represented in three dimensions by a back projection technique
      similar to maximum intensity projection. Potential advantages and drawbacks as
      compared to classical tractography are discussed; for example, it appears that
      our formulation handles naturally crossing tracts and is not biased by human
      intervention.

PMID- 16815714
TI  - Results after microfracture of full-thickness chondral defects in different
      compartments in the knee.
AB  - OBJECTIVE: To determine if the clinical results after microfracture of full
      thickness cartilage lesions deteriorate over a period of 36 months. METHODS:
      Between 1999 and 2002 85 patients (mean age 39.5 years) with full-thickness
      cartilage lesions underwent the microfracture procedure and were evaluated
      preoperatively and 6, 18 and 36 months after surgery. Exclusion criteria were
      meniscal pathologies, axial malpositioning and ligament instabilities. Baseline
      clinical scores were compared with follow-up data by paired Wilcoxon-tests for
      the modified Cincinnati knee and the International Cartilage Repair Society
      (ICRS)-score. The effects of the lesion localization and Magnetic resonance
      imaging (MRI) parameters were evaluated using the Pearson correlation and
      independent samples tests. RESULTS: Both scores revealed significant improvement
      18 months after microfracture (P<0.0001). Within the second 18 months after
      surgery there was a significant deterioration in the ICRS-score (P<0.0001). The
      best results could be observed in chondral lesions of the femoral condyles.
      Defects in other areas of the knee deteriorated between 18 and 36 months after
      microfracture. MRI 36 months after surgery revealed best defect filling in
      lesions on the femoral condyles with significant difference in the other areas
      (P<0.02). The Pearson coefficient of correlation between defect filling and ICRS
      score was 0.84 and significant at the 0.01 level. CONCLUSIONS: Microfracture is a
      minimal invasive method with good short-term results in the treatment of small
      cartilage defects. A deterioration of the results starts 18 months after surgery
      and is most evident in the ICRS-score. The best prognostic factors have young
      patients with defects on the femoral condyles.

PMID- 16815715
TI  - Viscoelastic properties of isolated rat colon smooth muscle cells.
AB  - The measurement of the biomechanical properties of gastrointestinal smooth muscle
      cells is important for the basic understanding of digestive function and the
      interaction of muscle cells with the matrix. Externally applied forces will
      deform the cells depending upon their mechanical properties. Hence, the evoked
      response mediated through stretch-sensitive ion-channels in the smooth muscle
      cell membrane will depend upon membrane properties and the magnitude of the
      external force. The aim of this study was to test the hypothesis that
      gastrointestinal smooth muscle cells behave in a viscoelastic manner. Smooth
      muscle cells were dissociated from the muscle layers of the descending colon. The
      viscoelastic properties of the isolated cells were characterized by measuring the
      mechanical deflection response of the cell membrane to a negative pressure of 1cm
      H(2)O applied across the cell through a micropipette and fitting the response to
      a theoretical viscoelastic solid model. The viscoelastic mechanical constants of
      the isolated cells (N=9) were found to be as follows: k(1)=19.99+/-2.86 Pa,
      k(2)=7.19+/-1.21 Pa, mu=25.36+/-6.14 Pas and tau=4.84+/-0.95 s. This study
      represents, to the best of our knowledge, the first quantitative mechanical
      properties of isolated living smooth muscle cells from the gastrointestinal
      tract. The mechanical properties determined in this study will be of use in
      future analytical and numerical smooth muscle cell models to better predict the
      mechanism between the magnitude of mechanical stimuli, mechanosensitivity and the
      evoked afferent responses.

PMID- 16815716
TI  - Analyzing the performance of conformational search programs on compound
      databases.
AB  - We have studied the sampling performance of conformational search programs using
      geometric and energetic criteria. Ideally, a conformational search algorithm
      should identify the largest possible number of low-energy structures (energy
      criterion) covering the widest possible range of molecular shapes (geometric
      criterion). Geometric analysis consisted in comparing the distribution of
      conformations within the generated ensembles by multidimensional scaling and by
      analysing the eigenvalue structure of the pairwise coordinate covariance
      matrices. The energetic comparison was carried out by assessing the energy
      distribution of conformers after minimizing them all using the same semi
      empirical quantum mechanics optimization protocol. The present investigation
      focused on five conformational search programs: DGEOM, QXP, ROTATE, LMOD and
      OMEGA. We have applied these methodologies to a maximally diverse 604-compound
      subset of the LeadQuest library. The program LMOD performs best according to the
      energetic criterion, whereas a wider range of geometrically diverse conformations
      is sampled by the other programs, at the cost of higher median conformer
      energies. In terms of speed, OMEGA is fastest. We recommend the use of LMOD or
      OMEGA for high-quality conformational search applications.

PMID- 16815717
TI  - Non-invasive measurement of oxygen partial pressure, lateral diffusion and
      chorioallantoic blood flow under the avian eggshell.
AB  - We measured P(O2) under the shell of avian eggs indirectly, by sealing 0.05 mL
      glass tubes to the shell, sealing them with mercury and using an oxygen
      microelectrode to measure the contained gas that equilibrates with the gas in the
      shell membranes. This technique requires a smaller area of contact with the shell
      and a shorter equilibration period than established techniques, and allows
      measurements at several locations simultaneously and over a long period of time
      without endangering the embryo. P(O2) under the shell of chicken eggs decreased
      to 14.3 kPa on the day before hatching (day 19). P(O2) was unstable during late
      development and differences up to 3.1 kPa occurred transiently on opposite sides
      of the equator. By waxing the shell around sampling tubes, we estimated Krogh's
      coefficient for lateral oxygen diffusion in the shell membranes at 1.1 mmol cm(
      1) d(-1) kPa(-1), a value about a third of a previous estimate. Sampling of gas
      under sufficiently large regions of waxed shell allowed indirect measurements of
      chorioallantoic venous P(O2), without affecting embryonic respiration. Venous
      P(O2) was 3.8 kPa on day 19. Assuming 14.3 kPa represents arterialized blood
      leaving the chorioallantois, it became possible to calculate the effective
      chorioallantoic blood flow rate, which was 3.5 mL min(-1) on day 19.

PMID- 16815718
TI  - The effects of age, season and geographic region on thyroid hormones in Steller
      sea lions (Eumetopias jubatus).
AB  - The purpose of this study was to investigate thyroid hormone concentrations,
      thyroxine (T4) and triiodothyronine (T3), in order to determine basal levels in
      Steller sea lions of different ages and over seasons. Serum concentrations of
      total T4 were highest in Steller sea lions followed by total T3 concentrations.
      Concentrations of free T4 and free T3 were three to four orders of magnitude
      lower. Concentrations for all four thyroid hormone measurements tended to a lower
      level as animals matured beyond the neonatal stage. When thyroid hormones from
      captive sea lions were evaluated across seasons, all thyroid hormones were
      highest in the July to September period. When compared across the geographic
      range, animals in southeast Alaska tended to have lower thyroid hormone levels,
      while the Steller sea lions west of Prince William Sound and animals from the
      Russian Far East had significantly higher concentrations. Significant inter
      annual differences in concentrations were also observed across the geographic
      range. With an understanding of the basic changes in thyroid hormone
      concentrations, changes in plane of nutrition or life history states (i.e.
      fasting, pregnancy or lactation) can now be evaluated for their effect on the
      overall health of this endangered species.

PMID- 16815719
TI  - Partial purification and characterization of cysteine proteinase inhibitor from
      chicken plasma.
AB  - A high-molecular-weight cysteine proteinase inhibitor (CPI) was purified from
      chicken (Gallus gallus) plasma using polyethylene glycol (PEG) fractionation and
      affinity chromatography on carboxymethyl-papain-Sepharose-4B. The CPI was
      purified 96.8-fold with a yield of 28.9%. Based on inhibitory activity staining
      for papain, CPI was shown to have an apparent molecular mass of 122 kDa. No
      inhibitory activity was obtained under reducing condition, indicating that CPI
      from chicken plasma was stabilized by disulfide bonds. CPI was stable in
      temperature ranges from 40 to 70 degrees C for 10 min; however, more than 50% of
      the inhibitory activity towards papain was lost within 30 min of heating at 90
      degrees C. CPI was stable in the presence of salt up to 3%. The purified CPI
      exhibited the inhibitory activity toward autolysis of arrowtooth flounder
      (Atheresthes stomias) and Pacific whiting (Merluccius productus) natural
      actomyosin (NAM) in a concentration-dependent manner.

PMID- 16815720
TI  - The effects of chronic immune stimulation on muscle growth in rainbow trout.
AB  - Successful production of aquaculture species depends on efficient growth with low
      susceptibility to disease. Therefore, selection programs have focused on rapid
      growth combined with disease resistance. However, chronic immune stimulation
      diminishes muscle growth (a syndrome referred to as cachexia), and decreases
      growth efficiency in production animals, including rainbow trout. In mammals,
      recent results show that increased levels of pro-inflammatory cytokines, such as
      those seen during an immune assault, specifically target myosin and MyoD and
      inhibit muscle growth. This suggests that increased disease resistance in fish, a
      desired trait for production, may actually decrease the growth of muscle, the
      main aquacultural commodity. To test this possibility, a rainbow trout model of
      cachexia was developed and characterized. A six-week study was conducted in which
      rainbow trout were chronically immune stimulated by repeated injections of LPS.
      Growth indices were monitored, and whole body and muscle proximate analyses, real
      time PCR, and Western blotting were conducted to examine the resulting cachectic
      phenotype. Muscle ratio was decreased in fish chronically immunostimulated,
      however expression levels of MyoD2 and myosin were not decreased compared to fish
      that were not immunostimulated, indicating that while muscle accretion was
      altered, the mechanism by which it occurred was somewhat different than that
      characterized in mammals. Microarray analysis was used to compare gene expression
      in fish that had been chronically immunostimulated versus those that had not to
      identify possible alternative mechanisms of cachexia in fish.

PMID- 16815721
TI  - Environmental signals implicated in Dr fimbriae release by pathogenic Escherichia
      coli.
AB  - Afa/Dr diffusely adhering Escherichia coli have been shown to cause urinary tract
      infections and enteric infections. Virulence of Dr-positive IH11128 bacteria is
      associated with the presence of Dr fimbriae. In this report, we show for the
      first time that the Dr fimbriae are released in the extracellular medium in
      response to multiple environmental signals. Production and secretion of Dr
      fimbriae are clearly thermoregulated. A comparison of the amounts of secreted
      fimbriae showed that the secretion is drastically increased during anaerobic
      growth in minimal medium. The effect of anaerobiosis on secretion seemed to
      depend on both the growth phase and the culture medium. The secretion was maximal
      during the logarithmic-phase growth and corresponded to 27 and 57% of total Dr
      fimbriae produced by bacteria grown in mineral medium+glucose and LB broth,
      respectively. Thus, the anaerobic environment of the colon would favour the
      secretion of Dr fimbriae during bacterial multiplication. The controlled release
      of the Dr fimbriae, which is carried out in the absence of cellular lysis,
      appears independent of the action of proteases or a process of maturation. The
      mechanism employed in the liberation of Dr fimbriae thus seems different from
      that described for the adhesins FHA and Hap of Bordetella pertussis and
      Haemophilus influenzae.

PMID- 16815722
TI  - Long polar fimbriae and tissue tropism in Escherichia coli O157:H7.
AB  - In vitro organ culture has demonstrated the human intestinal tropism of
      enterohaemorrhagic Escherichia coli O157:H7 for follicle associated epithelium
      overlying Peyer's patches of the terminal ileum. Long polar (LP) fimbriae are
      considered to mediate the attachment of Salmonella enterica serovar Typhimurium
      to Peyer's patch epithelium and, as homologous genes have been identified in
      O157:H7, we hypothesised that LP fimbriae in O157:H7 may perform the same
      function. However, mutation of LP fimbriae in O157:H7 strain 85/170 resulted in
      the novel phenotype of proximal and distal small intestinal colonisation with
      attaching/effacing lesion formation, while retaining adhesion to follicle
      associated epithelium. Application of whole genome DNA array technology did not
      identify changes in known fimbrial genes that could explain the change in
      tropism, but highlighted several genes that require further investigation. LP
      fimbrial genes are the first genes to be identified outside the locus of
      enterocyte effacement pathogenicity island that influence O157:H7 human
      intestinal tissue tropism.

PMID- 16815724
TI  - Superinfection of human immunodeficiency virus type 1 (HIV-1) to cell clone
      persistently infected with defective virus induces production of highly
      cytopathogenic HIV-1.
AB  - Superinfection with human immunodeficiency virus type 1 (HIV-1) in human
      subjects, defined as reinfection with a heterologous strain of HIV-1, has become
      a topic of great interest. To illustrate the significance of this occurrence, we
      performed HIV-1 superinfection of L-2 cells, which were isolated from MT-4 cells
      persistently infected with subtype B HIV-1 as a cell clone continuously producing
      defective HIV-1 particles. L-2 cells carrying provirus with a one-base insertion
      in the pol protease were superinfected with HIV-1 derived from primary isolates
      of subtype B or CRF01_AE. The kinetics of the superinfection in L-2 were very
      slow compared with those of primary infections in MT-4. Interestingly, L-2
      shifted after superinfection to become a producer of highly cytopathogenic HIV-1.
      Molecular characterization revealed that superinfection occurred in only about
      10% of the CRF01_AE-superinfected L-2, which carried provirus of both subtypes
      and produced viral particles containing genomic RNA of both subtypes.
      Surprisingly, such cytopathogenic HIV-1 showed predominantly the original subtype
      B phenotype. Thus, the mechanism of the production of cytopathic HIV-1 seemed to
      be mediated by trans complementation with pol products of superinfected CRF01_AE.
      These findings suggest the significance of long-lived infected cells as
      recipients for superinfection that could result in the generation of new HIV-1
      variants with high virulence in patients who are off therapy or do not adhere to
      treatment, and may indicate the need for precautions against such superinfection.

PMID- 16815723
TI  - Different signaling pathways are involved in cardiomyocyte survival induced by a
      Trypanosoma cruzi glycoprotein.
AB  - We have recently reported that Trypanosoma cruzi infection protects
      cardiomyocytes against apoptosis induced by growth factor deprivation. Cruzipain,
      a major parasite antigen, reproduced this survival effect by a Bcl-2-dependent
      mechanism. In this study, we have investigated the molecular mechanisms of
      cruzipain-induced cardiomyocyte protection. Neonatal BALB/c mouse cardiac
      myocytes were cultured under minimum serum conditions in the presence of
      cruzipain or T. cruzi (Tulahuen strain). Some cultures were pretreated with the
      phosphatidylinositol 3-kinase (PI3K) inhibitor Ly294002 or specific inhibitors of
      the mitogen-activated protein kinase (MAPK) family members such as the mitogen
      activated protein kinase kinase (MEK1) inhibitor PD098059, Jun N-terminal kinase
      (JNK) inhibitor SP600125, p38 MAPK inhibitor SB203580. Inhibition of PI3K and
      MEK1 but not JNK or p38 MAPK increased the apoptotic rate of cardiomyocytes
      treated with cruzipain. Phosphorylation of Akt, a major target of PI3K, and
      ERK1/2, MEK1-targets, was achieved at 15 min and 5 min, respectively. In
      parallel, these kinases were strongly phosphorylated by T. cruzi infection. In
      cultures treated with cruzipain, cleavage of caspase 3 was considerably
      diminished after serum starvation; Bcl-2 overexpression was inhibited by PD098059
      but not by Ly294002, whereas Bad phosphorylation and Bcl-xL expression were
      increased and differentially modulated by both inhibitors. The results suggest
      that cruzipain exerts its anti-apoptotic property in cardiac myocytes at least by
      PI3K/Akt and MEK1/ERK1/2 signaling pathways. We further identified a differential
      modulation of Bcl-2 family members by these two signaling pathways.

PMID- 16815725
TI  - Experimental transmission of Leishmania tropica to hyraxes (Procavia capensis) by
      the bite of Phlebotomus arabicus.
AB  - The ability of the sand fly Phlebotomus (Adlerius) arabicus to transmit
      Leishmania tropica was studied experimentally using hyraxes (Procavia capensis),
      natural reservoir hosts of the parasite. Sand flies became infected with L.
      tropica after feeding on a lesion of needle-inoculated hyrax. Moreover, P.
      arabicus fed with L. tropica promastigotes transmitted the parasite to hyraxes by
      bite during a second bloodmeal. Although the animals remained asymptomatic after
      infective sand fly bite, they were PCR positive and infectious for naive sand
      flies. We have thus demonstrated cyclical transmission of L. tropica by P.
      arabicus in hyraxes. This confirms experimentally the vectorial competence of P.
      (Adlerius) arabicus, and demonstrates that asymptomatic reservoir hosts are
      infectious to appropriate vectors.

PMID- 16815726
TI  - Protection of neonatal mice from lethal enterovirus 71 infection by maternal
      immunization with attenuated Salmonella enterica serovar Typhimurium expressing
      VP1 of enterovirus 71.
AB  - This study describes the potential use of attenuated Salmonella enterica serovar
      Typhimurium strains to express and deliver VP1 of enterovirus 71 (EV71) as a
      vaccination strategy to prevent EV71 infection in mice. When orally administered
      to BALB/c mice, both attenuated carrier strains, CNP101 and SL7207, were able to
      efficiently invade livers and spleens, while only the virulence plasmid-carrying
      strain SL7207 persisted for more than 30 days in these organs. A recombinant in
      vivo-regulated promoter expression plasmid expressing VP1 antigen of EV71 was
      constructed. The expression of the VP1, directed by the pagC promoter, in
      attenuated Salmonella was confirmed by Western blot hybridization. Both humoral
      and cellular immune responses were elicited in mice by oral immunization with
      such Salmonella-based VP1 vaccines. We evaluated the protective efficacy of the
      vaccines in mice using a maternal immunization protocol. With a lethal challenge,
      ICR newborn mice born to dams immunized with Salmonella-based VP1 vaccine showed
      a 50-60% survival; in contrast, none of the mice in the control group survived
      the challenge. Our data indicated that Salmonella-based VP1 subunit vaccines are
      a promising vaccine strategy in the prevention of EV71 infection.

PMID- 16815727
TI  - [Report and recommendation by the French Academy of Medicine concerning the
      prevention risks for the child to come and the necessity for early information
      before pregnancy].

PMID- 16815728
TI  - Hardware-in-the-loop-simulation of the cardiovascular system, with assist device
      testing application.
AB  - This paper presents a technique for evaluating the performance of biomedical
      devices by combining physical (mechanical) testing with a numerical, computerised
      model of a biological system. This technique is developed for evaluation of a
      cardiac assist device prior to in vivo trials. This device will wrap around a
      failing heart and provide physical beating assistance (dynamic cardiac
      compression). In vitro, the device to be tested is placed around a simulator
      comprising a mechanical simulation of the beating ventricles. This hardware model
      interfaces with a computerised (software) model of the cardiovascular system. In
      real time the software model calculates the effect of the assistance on the
      cardiovascular system and controls the beating motion of the hardware heart
      simulator appropriately. The software model of the cardiovascular system can
      represent ventricles in various stages of heart failure, and/or hardened or
      congested blood vessels as required. The software displays physiological traces
      showing the cardiac output, depending on the natural function of the modelled
      heart together with the physical assist power provided. This system was used to
      evaluate the effectiveness of control techniques applied to the assist device.
      Experimental results are presented showing the efficacy of prototype assist on
      healthy and weakened hearts, and the effect of asynchronous assist.

PMID- 16815729
TI  - Cerebral blood flow and oxygenation during head-up tilt in patients with multiple
      system atrophy and healthy control subjects.
AB  - To assess cerebral hemodynamics in patients with multiple system atrophy (MSA),
      cerebral blood flow and oxygenation were evaluated in 7 MSA patients and 9
      healthy controls during a head-up tilt test (HUT) by means of transcranial
      Doppler ultrasonography and near-infrared spectrophotometry. In the MSA patients
      examined, the perfusion pressure reduction during HUT was marked, but severe
      reduction in blood flow velocity was prevented because of a decrease in
      cerebrovascular resistance. The MSA patients showed no severe reduction in
      cerebral oxygenation during HUT. These findings indicate that our MSA patients
      exhibited a compensatory cerebral vasodilatation response to orthostatic
      hypotension.

PMID- 16815730
TI  - Mapping transactional sex on the Northern Corridor highway in Kenya.
AB  - Even in generalized HIV/AIDS epidemics, vulnerable populations such as sex
      workers and truckers require special attention in programming. Combining a number
      of elicitation methods, centred on Geographical Information Systems (GIS)
      mapping, the Kenyan section of the Northern Corridor highway was studied to
      characterize the 'hot spots' where transactional sex is concentrated and to
      provide estimates of numbers of truckers and sex workers and the volumes of
      transactional sex taking place on the highway. An average of 2400 trucks park
      overnight at the 39 hot spots identified. These spots have an estimated sex
      worker population of 5600 women. Analysis of 403 sex worker diaries shows an
      average of 13.6 different clients and 54.2 sex acts in a month. Condom use is 69%
      in liaisons with regular clients and 90% with casual clients. The use of GIS is
      demonstrated at regional and local scales. The 'bridge population' of clients of
      sex workers, containing a wide rage of occupations, supports the concept of
      programming for 'vulnerable places' as well as vulnerable groups.

PMID- 16815731
TI  - Community perspectives on the impact of policy change on linking social capital
      in a rural community.
AB  - Understanding what undermines or builds social capital is important when
      estimating the impact that changes in social capital have on people's lives. The
      aim of this paper is to illustrate how the consequences of neo-liberal policy
      initiatives have impacted on linking social capital in one small and vibrant
      rural community in Australia. Policy changes affecting all levels of government
      and various commercial agencies have undermined people's capability for a range
      of actions which bring personal and community-wide social and economic returns.
      Rationalisation and regionalisation of services and commercial agencies,
      including local government amalgamation, and increased workloads have undermined
      people's capabilities for community engagement. Policy outcomes are at odds with
      the stated policy agenda of building community capacity.

PMID- 16815732
TI  - Understanding mouse models of disease through metabolomics.
AB  - Metabolomics is widely applicable to a number of fields including toxicology,
      plant metabolism and functional genomics. In the area of functional genomics, a
      number of studies have demonstrated the potential of this approach, which
      combines high-throughput metabolite profiling with computer-assisted pattern
      recognition approaches. In this review, recent applications of metabolomics to
      understanding mouse models of disease are considered. This includes studies on
      the impact of mouse strain on disease models, as well as metabolic profiling of
      cardiovascular, metabolic and neurodegenerative diseases. This versatile tool is
      set to increase in popularity as functional genomic approaches produce more mouse
      models for phenotyping.

PMID- 16815733
TI  - Predictive value of in vitro safety studies.
AB  - The predictive value of in vitro safety studies is discussed for three important
      areas of pharmaceutical safety evaluations. In genetic toxicology, currently
      assays are sensitive for the prediction of cancer, but their overall predictive
      value is strongly diminished because of their low specificity. In the area of
      safety pharmacology blockage of hERG channel in vitro has recently been
      introduced to predict cardiac repolarization delay (QT interval prolongation) in
      patients. There is a plethora of in vitro methods to predict and characterize
      liver toxicity. However, little data is available that demonstrate a reliable
      prediction for hepatotoxicity in vivo over a wide range of chemical structures.
      In all three areas, further improvements are needed. 'Omics' technologies and new
      cell lines derived from stem cells are expected to strongly contribute to
      establish new and more predictive in vitro assays.

PMID- 16815734
TI  - Cyclophilin, TRIM5, and innate immunity to HIV-1.
AB  - The peptidyl-prolyl isomerase cyclophilin A (CypA) binds a proline-rich loop on
      the surface of HIV-1 capsid (CA). This interaction increases HIV-1 infectivity in
      humans but promotes an anti-HIV-1 restriction activity in non-human primates.
      Efforts to understand these paradoxical effects of cyclophilin, along with more
      targeted approaches to uncover the genetic basis for HIV-1 restriction, led to
      the discovery of TRIM5 (tripartite motif protein 5), a CA-specific receptor for
      the retroviral core. The ensuing TRIM5 publication flurry established a paradigm
      of innate immunity in which the protein lattice of an invading retroviral core,
      rather than double-stranded RNA or lipopolysaccharide, is recognized by a
      multimeric, cytoplasmic receptor. CypA modulates HIV-1 virion core detection by
      this class of innate pattern recognition molecule, apparently by inducing subtle
      shifts in CA conformation.

PMID- 16815735
TI  - Viruses and sumoylation: recent highlights.
AB  - Since its discovery in 1997, SUMO (small ubiquitin-like modifier) has been
      implicated in a range of activities, indicating that this protein is as important
      in the cell as ubiquitin is. Although it can function throughout the cell, it
      appears to be involved more in nuclear functions. The growing list of substrates
      that are covalently modified by SUMO includes many viral proteins; SUMO appears
      to facilitate viral infection of cells, making it a possible target for antiviral
      therapies. It therefore is important to understand how viruses manipulate the
      cellular sumoylation system and how sumoylation affects viral functions.

PMID- 16815736
TI  - Human red blood cell polymorphisms and malaria.
AB  - Genetic factors are a major determinant of child survival in malaria endemic
      countries. Identifying which genes are involved and how they affect the malaria
      disease risk potentially offers a powerful mechanism through which to learn more
      about the host-parasite relationship. The past few years have seen significant
      progress towards achieving this goal for some of the best-known malaria
      resistance genes that determine the structure or function of red blood cells:
      Gerbich blood group antigen negativity; polymorphisms of the complement receptor
      genes (most notably CR1); Southeast Asian ovalocytosis; pyruvate kinase
      deficiency; haemoglobin E; the sickle cell trait; and alpha-thalassaemia are all
      examples. The challenge for the future must be to translate such advances into
      fresh approaches to the prevention and treatment of malaria.

PMID- 16815737
TI  - Micronucleus studies in the peripheral blood and bone marrow of mice treated with
      jet fuels, JP-8 and Jet-A.
AB  - The potential adverse effects of dermal and inhalation exposure of jet fuels are
      important for health hazard evaluation in humans. The genotoxic potential of jet
      fuels, JP-8 and Jet-A, was investigated in an animal model. Mice were treated
      dermally with either a single or multiple applications of these jet fuels.
      Peripheral blood and bone marrow smears were prepared to examine the incidence of
      micronuclei (MN) in polychromatic erythrocytes (PCEs). In all experiments, using
      several different exposure regimens, no statistically significant increase in the
      incidence of MN was observed in the bone marrow and/or peripheral blood of mice
      treated with JP-8 or Jet-A when compared with those of untreated control animals.
      The data in mice treated with a single dose of JP-8 or Jet-A did not confirm the
      small but statistically significant increase in micronuclei reported in our
      previous study.

PMID- 16815738
TI  - A method for determining information flow breakdown in clinical systems.
AB  - This paper presents Determining Information flow Breakdown (DIB), a method for
      analyzing adverse events in clinical environments from the perspective of
      breakdowns in information flow. The larger context for DIB is that it is the
      first stage in a process that promotes organizational learning in response to
      adverse events through the design of novel IT solutions. DIB is based on the
      theoretical view of distributed cognition and adopts a system-wide view of
      failures. DIB is both a reactive and a proactive method in that it aims to locate
      the causes of either actual or potential adverse events by investigating all
      elements of the system related to a chosen aspect of patient care. It was
      developed and evolved using a case study approach whereby data on actual and
      potential adverse events in clinical environments was collected, modeled and
      analyzed using successive versions of the method. We provide an explanation and
      overview of the DIB method, and discuss our experiences of applying it in
      practice via a detailed example.

PMID- 16815740
TI  - To decay is system: the challenges of keeping a health information system alive.
AB  - Health information system (HIS) architecture and socio-technical approaches for
      system deployment have been topics of systematic research for decades.
      Sustainable operation in gradually changing environments, however, has not yet
      received sufficient attention. Even HIS that have gone life to the satisfaction
      of their developers and end-users may degrade gracefully or fail catastrophically
      if not continuously and thoroughly kept in sync with their environment. Critical
      environmental changes may owe their origins to the complexity of health care and
      its delivery. Seemingly minor environmental changes can result in significant
      failures on the part of the information system and may adversely affect the
      quality of health care delivered. Such minor degradation or near failure may go
      unnoticed for a while and then hit unexpectedly. Five origins of decay will be
      analyzed. Methods of systematic observation and containment of such decaying
      processes will tentatively be presented. Some origins of system decay exist in
      the immediate hospital or regional setting of usage. Indicators to identify
      processes of decay will be suggested and methods to preemptively reduce the risk
      of decay will be presented. Other origins span national health care systems or
      beyond. Not all such risks can hence be controlled locally. Software Oversight
      Committees may be an instrument to monitor those risks that cannot be controlled
      through routine local management.

PMID- 16815739
TI  - Using argumentation to extract key sentences from biomedical abstracts.
AB  - PROBLEM: key word assignment has been largely used in MEDLINE to provide an
      indicative "gist" of the content of articles and to help retrieving biomedical
      articles. Abstracts are also used for this purpose. However with usually more
      than 300 words, MEDLINE abstracts can still be regarded as long documents;
      therefore we design a system to select a unique key sentence. This key sentence
      must be indicative of the article's content and we assume that abstract's
      conclusions are good candidates. We design and assess the performance of an
      automatic key sentence selector, which classifies sentences into four
      argumentative moves: PURPOSE, METHODS, RESULTS and CONCLUSION:  METHODS: we rely
      on Bayesian classifiers trained on automatically acquired data. Features
      representation, selection and weighting are reported and classification
      effectiveness is evaluated on the four classes using confusion matrices. We also
      explore the use of simple heuristics to take the position of sentences into
      account. Recall, precision and F-scores are computed for the CONCLUSION class.
      For the CONCLUSION class, the F-score reaches 84%. Automatic argumentative
      classification using Bayesian learners is feasible on MEDLINE abstracts and
      should help user navigation in such repositories.

PMID- 16815741
TI  - Development and evaluation of a patient-oriented education system for diabetes
      management.
AB  - PURPOSE: To develop and evaluate a Web-based, patient-orientated diabetic
      education management (POEM) system. METHODS: The POEM system has been developed
      to extend hospital patient education by integrating patients' medical care data
      into their education program components and presenting them on the Web. Since
      most patients are concerned about their medical care data, the POEM system can
      provide the incentives for patients to continuously and persistently log in and
      learn the required knowledge and skills, improving their clinical outcomes. A
      quasi-experimental method that uses control groups and pretests was used to
      evaluate the outcomes of the system intervention. We recruited patients with type
      2 diabetes and alternatively assigned them to intervention and control groups. We
      compared laboratory test results including fasting blood glucose, HbA1c, total
      cholesterol, triglyceride (TG), and HDL between the two groups from the first
      visit through each follow-up visit. The study period progressed from September
      2003 to May 2004 at the Metabolism Center of a medical teaching hospital in
      Taipei. RESULTS: In this study, we recruited 274 participants: 134 (57% males and
      43% females) in the intervention group and 140 (46% males and 54% females) in the
      control group. The patients' laboratory test results from the first visit for
      fasting blood glucose, HbA1c, total cholesterol level, TG, and HDL in the
      intervention and control groups were respectively 187.54+/-77.10 and 189.99+/
      73.49 mg/dl, 9.03 +/- 2.79% and 8.95 +/- 2.23%, 193.29 +/- 47.93 and 202.52 +/-
      58.45 mg/dl, 152.48 +/- 70.85 and 157.37 +/- 74.88 mg/dl, and 44.97 +/- 12.09 and
      45.32 +/- 12.08 mg/dl. There were three follow-up visits during the study period.
      We collected laboratory test results of the two groups through each of the
      following visits and analyzed them using ANCOVA. We discovered a significant
      difference in fasting blood glucose levels between intervention and control group
      as early as the first follow-up. At the second follow-up, both fasting blood
      glucose and HBA1c levels were significantly different between intervention and
      control group. At the third follow-up, there was a significant difference in
      fasting blood glucose, HBA1c, and total cholesterol between intervention and
      control group. We also monitored the number of logins for the patients in the
      intervention group during the follow-up period. The result showed the patients
      had consistently logged into the POEM system (about 8.5 +/- 3.7 logins per person
      per month after 3 months enrollment). Thus, the patients in the intervention
      group had better control of their fasting blood glucose, HbA1c and total
      cholesterol levels than those in the control group due to the assistance of the
      system. CONCLUSIONS: The POEM system can help patients control their glucose,
      HbA1c and total cholesterol levels to manage their diabetes, providing an easy
      and inexpensive way to extend hospital-based patient education services for
      community-based continuous patient education.

PMID- 16815742
TI  - Evidence for direct transfer of cytoplasmic material from infected to uninfected
      cells during cell-associated spread of human cytomegalovirus.
AB  - Cell-associated spread is assumed to be the predominant mode of human
      cytomegalovirus (HCMV) dissemination in infected patients, however the underlying
      mechanisms are poorly understood. We tested the hypothesis that cell-to-cell
      spread of HCMV may be associated with direct transfer of cytoplasmic material by
      analyzing focal growth of green fluorescent HCMVDeltaUL16GFP. In this recombinant
      virus, UL16 was partially replaced by the green fluorescent protein (EGFP). The
      resulting HCMVDeltaUL16GFP showed unrestricted growth and expressed EGFP from the
      early UL16 promoter. EGFP transmission was then investigated in relation to viral
      spread from productively infected cells to cocultured uninfected cells.
      Alternatively, microinjection of fluorescent dextrane allowed for direct
      visualization of inter-cell-connections. Within 5h of coculture, 8% of cells
      neighbouring productively infected cells had acquired EGFP. Detection of EGFP in
      the absence of IE antigen and during cycloheximide block excluded the possibility
      of de novo synthesis. Immediate distribution of microinjected fluorescent dyes
      from infected cells to adjacent cells proved the existence of cell-cell-fusions.
      These data demonstrate that focal spread of HCMV is associated with direct
      transfer of cytoplasmic material, most likely through cell-cell-fusions. This
      would withdraw the virus from the control of neutralizing antibodies and thus
      provide an explanation for the limited antiviral effect of the humoral immune
      response.

PMID- 16815743
TI  - An AFM investigation of oligonucleotides anchored on unoxidized crystalline
      silicon surfaces.
AB  - Carboxylic terminated monolayers have been covalently attached on phosphorous
      doped crystalline (100) silicon surfaces using a cathodic electro grafting
      technique. The functionalization concentration and efficiency have been evaluated
      with different techniques. In particular, topographic images, performed with an
      atomic force microscope, were used to optimize the protocol in order to obtain a
      surface whose characteristics of uniformity and reproducibility are ideal for a
      bio-electronic device. Phase lag images of the functionalized surfaces were also
      performed, and show non-topographic structures that have been interpreted as
      areas of different molecule self-orientation. Poly-thymine oligonucleotides have
      been anchored on such a surface to form a nano-biosensing device capable to react
      selectively with a specific target molecule, a poly-adenine oligonucleotide. AFM
      images of high density (approximately 3x10(12) mol/cm2) single strand and double
      strand covered samples show toroidal shaped structures formed by the self
      assembly of the oligonucleotides on the silicon surface.

PMID- 16815744
TI  - Efficacy and safety of zolpidem-MR: a double-blind, placebo-controlled study in
      adults with primary insomnia.
AB  - BACKGROUND AND PURPOSE: To evaluate the clinical efficacy and safety of modified
      release zolpidem (zolpidem-MR 12.5mg) for the treatment of primary insomnia in
      adults. PATIENTS AND METHODS: Two hundred and twelve (123 women, 89 men; mean age
      44.3+/-SD 3.0 years), Diagnostic and Statistical Manual of Mental Disorders--4th
      Edition (DSM-IV)-defined primary insomnia patients were randomized in a double
      blind, placebo-controlled, parallel-group study. The study was completed by 192
      patients. Patients received 3 weeks of nightly treatment with either zolpidem-MR
      12.5mg or placebo, preceded and followed by two nights of single-blind placebo.
      The main outcome measures were mean polysomnographic (PSG) sleep parameters of
      nights 1/2 and nights 15/16 of double-blind treatment and daily subjective sleep
      estimates from sleep questionnaires to assess efficacy, and PSG parameters of
      nights 22 and 23 of single-blind placebo substitution to assess the effect of
      drug discontinuation. RESULTS: Relative to placebo, zolpidem-MR 12.5mg improved
      sleep maintenance by significantly reducing PSG wake time after sleep onset
      (WASO) during the first 6h of sleep as well as the number of awakenings.
      Consistent with the effects of standard zolpidem, zolpidem-MR also significantly
      reduced latency to persistent sleep, and significantly increased sleep
      efficiency, both at the beginning and after 2 weeks of double-blind treatment.
      There was no evidence of next-day residual effects as measured objectively by
      psychometric tests. Rebound insomnia on the first night after abrupt
      discontinuation resolved the following night. Overall, zolpidem-MR was well
      tolerated. CONCLUSIONS: Zolpidem-MR 12.5mg is effective and safe in treating
      primary insomnia in adults and improves sleep maintenance, induction and duration
      of sleep.

PMID- 16815746
TI  - Sleep deprivation and hormone therapy in postmenopausal women.
AB  - BACKGROUND AND PURPOSE: Sleep complaints increase after menopause, but literature
      on the effect of postmenopausal hormone therapy (HT) on sleep is controversial.
      The purpose of this study was to determine the effect of ageing and HT on sleep
      quality, assessed using polysomnography, and on the accuracy of the subjective
      estimation of sleep quality in women before and after sleep deprivation. PATIENTS
      AND METHODS: Twenty postmenopausal women (aged 58-72 years) were recruited: 10 HT
      users and 10 non-HT-users. Eleven young women (aged 20-26 years) served as
      controls. Polysomnography and subjective sleep quality were measured on four
      consecutive nights: adaptation, baseline, 40-h sleep deprivation and recovery.
      RESULTS: Although the postmenopausal women slept worse than the controls at
      baseline, and in particular during the recovery night, their recovery response to
      sleep deprivation was well preserved. At baseline, HT-users had a shorter latency
      to rapid eye movement (REM) (P=0.043), with fewer awakenings from slow wave sleep
      (SWS) (P=0.029) but more from REM (P=0.033) than non-HT-users. During recovery,
      the HT-users had more stage 2 sleep (P=0.048) and less slow wave activity (SWA)
      in the first non-rapid eye movement (NREM) sleep episode (P=0.021) than the non
      HT-users. The poor correlation between subjective and objective sleep quality at
      baseline became significant during recovery. CONCLUSIONS: Although sleep in
      postmenopausal women was worse than in young controls, the recovery response
      following sleep deprivation was relatively well preserved. HT offered no
      significant advantage to sleep at baseline and slightly weakened the recovery
      response to prolonged wakefulness.

PMID- 16815745
TI  - Daytime sleepiness with and without cataplexy in Chinese-Taiwanese patients.
AB  - BACKGROUND AND PURPOSE: Investigation of Chinese-Taiwanese patients with
      excessive sleepiness, but no association with other sleep disorders, and with the
      presence or absence of cataplexy. PATIENTS AND METHODS: Thirty-five patients,
      successively referred between 2002 and 2004, underwent polysomnography (PSG),
      repeat multiple sleep latency test (MSLT), and human leukocyte antigen (HLA)
      typing. Three patients without cataplexy also had cerebrospinal fluid (CSF)
      hypocretin measurements. RESULTS: DQB1*0602 was associated with cataplexy in over
      90% of Chinese-Taiwanese cases. Absence of cataplexy and <2 sleep-onset REM
      periods (SOREMPs) was seen in only two subjects, but presence of two SOREMPs did
      not dissociate DQB1*0602 positive and negative or cataplexy positive and negative
      subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs,
      and the mean sleep latency was much shorter in narcoleptics with cataplexy than
      in the non-cataplectic patients, independent of the number of SOREMPs.
      CONCLUSIONS: Chinese-Taiwanese patients with cataplexy present with similar HLA
      findings as Black and Caucasian patients, but the presence of two or more SOREMPs
      in Chinese-Taiwanese patients is not a sufficient diagnostic tool to identify
      narcolepsy. When cataplexy is not present, description of PSG nd HLA findings may
      be a better approach than using a label with little scientific significance,
      allowing for better collection of patients' phenotype.

PMID- 16815747
TI  - Lucid dreaming during Multiple Sleep Latency Test (MSLT).

PMID- 16815748
TI  - Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a
      polysomnographic dose-finding study--the PRELUDE study.
AB  - BACKGROUND AND PURPOSE: To evaluate the effects of pramipexole (0.125-0.75 mg/d)
      on polysomnographic (PSG) measures and patient and clinician ratings of restless
      legs syndrome (RLS). PATIENTS AND METHODS: Patients (n=109) with moderate to
      severe RLS were randomized to placebo or fixed doses of pramipexole during a 3
      week, double-blind, placebo-controlled, dose-finding study. RESULTS: In each
      pramipexole dose group, the periodic limb movements during time in bed index
      (PLMI) decreased significantly, compared with placebo (adjusted mean difference
      in log-transformed data: 0.125 mg, -1.54; 0.25 mg, -1.93; 0.50 mg, -1.89; and
      0.75 mg, -1.52; P<0.0001). At all doses, International RLS Study Group Rating
      Scale (IRLS) scores were also significantly reduced, with the greatest adjusted
      mean reduction in the 0.50mg group (-17.01). At all but the lowest pramipexole
      dose, the percentage of responders (> or =50% reduction of IRLS score) was
      substantially higher than for placebo (61.9-77.3, vs 33.3%). In the pramipexole
      groups, 50.0-77.3% of patients rated their condition as 'much better' or 'very
      much better', compared with 38.1% of patients in the placebo group (P=0.0139 for
      the 0.50 mg dose). Clinical global impressions (CGI) scale ratings of 'much
      improved' or 'very much improved' were given to 61.9-86.4% of patients in the
      pramipexole groups, compared with 42.9% in the placebo group (P<0.05 for the
      0.25, 0.50, and 0.75 mg groups). Pramipexole was well tolerated and did not
      produce somnolence at any dose. CONCLUSION: Pramipexole is effective and safe in
      the treatment of both objective and subjective facets of RLS.

PMID- 16815749
TI  - Studio Morfeo 2: survey on the management of insomnia by Italian general
      practitioners.
AB  - BACKGROUND AND PURPOSE: To carry out an observational epidemiological survey
      (Studio Morfeo 2) in order to define the management procedures of insomnia in a
      large Italian population presenting directly to the general practitioner (GP).
      PATIENTS AND METHODS: Each GP recruited five insomniac subjects in the course of
      1 week or 5 consecutive office days over a period of 2 weeks. On each office day,
      a brief questionnaire (Q1) including five questions investigating insomnia
      symptoms and current use of treatment was administered to the first 10 patients
      who referred to the GP office for reasons associated with their own health. The
      first patient of each day classified as insomniac underwent a second
      investigation based on a more detailed questionnaire (Q2) including demographic
      variables, socio-economic status, general medical conditions, severity, duration
      and clinical features of insomnia, daytime dysfunction, sleep satisfaction and
      therapeutic management. RESULTS: In a primary care setting, insomnia symptoms are
      often persistent (>1 year), recurrent (>1/week) and accompanied by daytime
      consequences. Two out of three patients with insomnia symptoms are dissatisfied
      with their sleep. In most cases, insomnia symptoms are underrated both by the
      patients, who cover the problem or reject treatment, and by the GP, who limits
      intervention on the sleep disorder (scarcely modifying ongoing therapy both in
      responders and in non-responders). In responders, treatment was confirmed in 91%
      of cases and discontinued in only 2%. When there was no improvement, or if
      insomnia symptoms became worse (non-responders), treatment was nevertheless
      continued in 74.5% of cases, either maintaining the same ineffective dose,
      increasing the dose, or adding another drug or a non-pharmacological procedure.
      Regardless of specific medication, the Italian GP privileges the pharmacological
      approach, which is fourfold more frequent than non-pharmacological therapy (78.6
      versus 18.2%). Non-benzodiazepine hypnotic drugs are mostly prescribed when the
      GP decides to apply medication in previously untreated patients with insomnia
      symptoms. Self-administration is not unusual among the patients with insomnia
      symptoms and is more common among non-responders. CONCLUSIONS: Italian GPs tend
      to confirm the ongoing therapy and avoid re-evaluation of the treatment regimen.
      Limited use of non-pharmacological treatment in the Italian primary care setting
      is in line with this conservative approach of the GPs who tend to be problem
      solvers rather than problem-seekers.

PMID- 16815750
TI  - Correlates of daytime sleepiness in patients with asthma.
AB  - BACKGROUND AND PURPOSE: Patients with asthma often complain of daytime
      sleepiness, which is usually attributed to a direct effect of asthma on nocturnal
      sleep quality. We investigated this and other potential explanations for daytime
      sleepiness among asthmatics. PATIENTS AND METHODS: One hundred fifteen adult
      asthmatics were assessed for perceived daytime sleepiness (one question item),
      subjective sleepiness (Epworth Sleepiness Scale score, ESS), obstructive sleep
      apnea risk (Sleep Apnea scale score within Sleep Disorders Questionnaire, SA
      SDQ), asthma severity step, relevant comorbid conditions, and current asthma
      medications. RESULTS: Among all subjects, 55% perceived excessive daytime
      sleepiness and 47% had ESS>10. Most subjects reported snoring (n=99, or 86%) and
      many snored habitually (n=44, 38%). The ESS correlated with SA-SDQ (P<0.0001),
      male gender (P=0.01), and asthma severity step (P=0.04). In a multiple regression
      model, the ESS was independently associated with SA-SDQ (P=0.0003) and male
      gender (P=0.02), but not with asthma severity step (P=0.51). There were no
      correlations between ESS and age, body mass index (BMI), forced expiratory volume
      in one second as percent of predicted value (FEV(1)%), comorbidities, or
      medication used to treat asthma. CONCLUSIONS: Sleepiness is common in asthmatics
      and may reflect occult obstructive sleep apnea more often than effects of asthma
      itself, other comorbid conditions, or asthma medications.

PMID- 16815751
TI  - Use of pramipexole in REM sleep behavior disorder: results from a case series.
AB  - BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep behavior disorder (RBD)
      has a known association with other medical conditions, including narcolepsy and
      neurodegenerative diseases such as synuclienopathies. RBD is currently treated
      with clonazepam as a first-line therapy. Recent research suggests that the
      pathophysiology underlying RBD may involve a dopaminergic deficiency, given its
      association with Parkinson syndromes and restless legs syndrome (RLS). We report
      on the efficacy of pramipexole, a dopaminergic D2-3 receptor agonist, in the
      treatment of RBD. PATIENTS AND METHODS: The first 10 consecutive patients
      presenting with a history and polysomnographically confirmed RBD were given
      pramipexole as either a single dose before bedtime or as a divided dose regimen
      with the first dose given in the early evening and the second dose at bedtime.
      Medication was titrated to control RBD symptoms and the clinical response was
      monitored through interviews with the patient, spouse, and close family members
      during the course of the study at regularly scheduled follow-up visits. RESULTS:
      The mean length of treatment was 13.1 months, and the average total evening dose
      of pramipexole at the end of the study was 0.89+/-0.31 mg. A divided dose regimen
      of pramipexole was used in 56% of patients remaining on pramipexole. We found
      that 89% of patients experienced either a moderate reduction or complete
      resolution in the frequency of RBD symptoms throughout the duration of the study.
      Moreover, 67% reported at least a moderate reduction in the severity of remaining
      symptoms. CONCLUSIONS: Pramipexole markedly reduced the frequency and severity of
      RBD symptoms and appeared to maintain efficacy for up to 25 months as assessed at
      follow-up visits. Clonazepam may have numerous unwanted side effects in the
      elderly or narcoleptics with RBD, such as prominent sedation and the potential
      exacerbation of underlying obstructive breathing in sleep. The potential role of
      pramipexole in improving RBD and its associated dopamine deficient syndromes
      warrants further research in the use of dopaminergic agonists as a potential
      first-line alternative therapy for RBD.

PMID- 16815752
TI  - Iron and restless legs syndrome: the story unfolds.

PMID- 16815753
TI  - Obstructive sleep apnea-hypopnea and neurocognitive functioning in the Sleep
      Heart Health Study.
AB  - BACKGROUND AND PURPOSE: Obstructive sleep apnea-hypopnea (OSAH) is associated
      with sleep fragmentation and nocturnal hypoxemia. In clinical samples, patients
      with OSAH frequently are found to have deficits in neuropsychological function.
      However, the nature and severity of these abnormalities in non-clinical
      populations is less well defined. PATIENTS AND METHODS: One hundred and forty-one
      participants from the Tucson, AZ and New York, NY field centers of the Sleep
      Heart Health Study completed a battery of neuropsychological tests for 9-40
      months (mean=24 months, SD=7 months) after an unattended home polysomnogram.
      Sixty-seven participants had OSAH (AHI>10) and 74 did not have OSAH (control
      (CTL), apnea-hypopnea index (AHI)<5). In addition to the individual tests,
      composite variables representing attention, executive function, MotorSpeed and
      processing speed were constructed from the neuropsychological test battery.
      RESULTS: There were no significant differences in any individual
      neuropsychological test or composite variable between the OSAH and CTL groups.
      However, when time spent with O(2) saturations less than 85% was dichotomized
      into those participants in the top quartile of the distribution and those in the
      lower three quartiles, motor speed was significantly impaired in those who were
      more hypoxemic. In addition, poorer motor speed (model adjusted R(2)=0.242,
      P<0.001) and processing speed performance (model adjusted R(2)=0.122, P<0.001)
      were associated with more severe oxygen desaturation even after controlling for
      degree of daytime sleepiness, age, gender and educational level. CONCLUSIONS:
      Mild to moderate OSAH has little impact on the selected measures of attention,
      executive function, motor speed and processing speed. However, hypoxemia
      adversely affects both motor and processing speed. These results suggest that in
      middle-aged to elderly adults the neuropsychological effects of clinically
      unrecognized mild to moderate OSAH are neither global nor large.

PMID- 16815754
TI  - Fatal multidrug-resistant Acinetobacter baumannii sepsis in a patient with travel
      history and recent onset of systemic lupus erythematosus: a case report.
AB  - Severe infections are a common cause of death in patients suffering from systemic
      lupus erythematosus (SLE). We here report on a fatal multidrug-resistant
      Acinetobacter baumannii sepsis in a patient with newly diagnosed SLE, who had to
      be treated with immunosuppressants due to lupus nephritis. Detailed analysis of
      the patient's history revealed that colonisation probably had occurred during a
      recent hospitalisation of the patient in the Mediterranean region. E-test
      analysis indicated that resistance to carbapenems was mediated by a plasmid
      encoded metallo-beta-lactamase. We conclude that travel history including
      previously visited health care facilities always should be carefully considered
      for decisions on anti-infective therapy, as travel activities increasingly
      facilitate spread of antimicrobial resistances.

PMID- 16815755
TI  - Emergency aortic valve replacement in systemic lupus erythematosus.
AB  - The valvular heart disease in systemic lupus erythematosus (SLE) is associated
      with substantial morbidity and mortality. Current therapy includes symptomatic
      measures and valve replacement. Overall mortality of valve replacement has been
      reported to be as high as 25%. Most cases of Libman-Sacks endocarditis in the
      literature reported dominant aortic regurgitation. We present this unusual case
      of a young female patient with SLE and glomerulonephritis warranting emergency
      isolated aortic valve replacement (AVR) for severe calcific aortic stenosis. The
      literature is reviewed with specific focus on the pathogenesis of and acute
      treatment options for this extremely rare occurrence.

PMID- 16815756
TI  - The DRiP hypothesis decennial: support, controversy, refinement and extension.
AB  - In 1996, to explain the rapid presentation of viral proteins to CD8+ T cells, it
      was proposed that peptides presented by MHC class I molecules derive from
      defective ribosomal products (DRiPs), presumed to be polypeptides arising from in
      frame translation that fail to achieve native structure owing to inevitable
      imperfections in transcription, translation, post-translational modifications or
      protein folding. Here, we consider findings that address the DRiP hypothesis, and
      extend the hypothesis by proposing that cells possess specialized machinery,
      possibly in the form of "immunoribosomes", to couple protein synthesis to antigen
      presentation.

PMID- 16815757
TI  - Experiences with frozen blood products in the Netherlands military.
AB  - For peacekeeping and peace enforcing missions abroad the Netherlands Armed Forces
      decided to use universal donor frozen blood products in addition to liquid
      products. This article describes our experiences with the frozen blood inventory,
      with special attention to quality control. It is shown that all thawed (washed)
      blood products are in compliance with international regulations and guidelines.
      By means of the -80 degrees C frozen stock of red cells, plasma and platelets
      readily available after thaw (and wash), we can now safely reduce shipments and
      abandon the backup 'walking' blood bank, without compromising the availability of
      blood products in theatre.

PMID- 16815758
TI  - Spectacularly robust! Tensegrity principle explains the mechanical strength of
      the avian lung.
AB  - Among the air-breathing vertebrates, the respiratory system of birds, the lung
      air sac system, is remarkably complex and singularly efficient. The most
      perplexing structural property of the avian lung pertains to its exceptional
      mechanical strength, especially that of the minuscule terminal respiratory units,
      the air- and the blood capillaries. In different species of birds, the air
      capillaries range in diameter from 3 to 20 micro m: the blood capillaries are in
      all cases relatively smaller. Over and above their capacity to withstand enormous
      surface tension forces at the air-tissue interface, the air capillaries resist
      mechanical compression (parabronchial distending pressure) as high as 20 cm H(2)O
      (2 kPa). The blood capillaries tolerate a pulmonary arterial vascular pressure of
      24.1 mmHg (3.2 kPa) and vascular resistance of 22.5 mmHg (3 kPa) without
      distending. The design of the avian respiratory system fundamentally stems from
      the rigidity (strength) of the lung. The gas exchanger (the lung) is uncoupled
      from the ventilator (the air sacs), allowing the lung (the paleopulmonic
      parabronchi) to be ventilated continuously and unidirectionally by synchronized
      bellows like action of the air sacs. Since during the ventilation of the lung the
      air capillaries do not have to be distended (dilated), i.e., surface tension
      force does not have to be overcome (as would be the case if the lung was
      compliant), extremely intense subdivision of the exchange tissue was possible.
      Minuscule terminal respiratory units developed, producing a vast respiratory
      surface area in a limited lung volume. I make a case that a firm (rigid) rib
      cage, a lung tightly held by the ribs and the horizontal septum, a lung directly
      attached to the trunk, specially formed and compactly arranged parabronchi,
      intertwined atrial muscles, and tightly set air capillaries and blood capillaries
      form an integrated hierarchy of discrete network system of tension and
      compression, a tensegrity (tensional integrity) array, which absorbs, transmits,
      and dissipates stress, stabilizing (strengthening) the lung and its various
      structural components.

PMID- 16815759
TI  - Pleural liquid during hemorrhagic hypotension.
AB  - The effect of approximately 25% or 35% blood loss (b.l.) on volume, pressure, and
      protein concentration of pleural liquid has been determined in anesthetized
      rabbits in lateral or supine posture. Volume and pressure of pleural liquid did
      not change with 25% b.l. 30 and 60 min after beginning of hemorrhage, and with
      35% b.l. at 30 min (bleeding time approximately 10 and 12 min, respectively).
      With 35% b.l. protein concentration of pleural liquid was 85% greater (P<0.01)
      than control; moreover, percent albumin was smaller (P<0.05), and percent
      globulin greater (P<0.05) than control. Decrease in arterial plasma protein
      concentration, hematocrit, and pH after hemorrhage fit literature data.
      Ventilation at 15 and 30 min increased (P<0.01) by 16% and 23%, respectively,
      with 25% b.l., but it did not change with 35% b.l., a condition borderline to
      survival in anesthetized rabbits without ad hoc treatment. Pleural liquid seems
      protected against derangements from hemorrhage up to 25% b.l. for periods shorter
      than 1 h.

PMID- 16815760
TI  - Correlations between the circadian patterns of body temperature, metabolism and
      breathing in rats.
AB  - It had been demonstrated previously that the circadian patterns of activity and
      state of arousal are not essential for the manifestation of the daily patterns of
      pulmonary ventilation (V(E)), tidal volume (V(T)) and breathing frequency (f). In
      this study we investigated the extent of the linkage between the circadian
      pattern of breathing and those of body temperature (T(b)) and metabolic rate
      (oxygen consumption, V(O2), and carbon dioxide production, V(CO2)). Rats were
      instrumented for measurements of T(b) (by telemetry), and placed in a chamber for
      continuous 13-day period of measurement of breathing (by a modification of the
      barometric methodology), and of V(O2) and V(CO2) (by an open flow method). After
      the first 4 days in control conditions under a 12 h light:12 h dark (L:D) cycle,
      a perturbation was introduced on day 4, with an L-phase prolongation of 12 h, and
      on day 9, with an D-phase prolongation of 12 h. During the control days 1-4, all
      variables had daily oscillations (higher values in D), in phase with each other.
      During the perturbations (days 4-13), changes in T(b), V(O2) and V(CO2), averaged
      over the whole period, correlated significantly better with f than with V(T). Day
      by-day X-Y loops indicated that V (E), V(T) and f could lead significantly the
      changes of T(b), V(O2) and V(CO2), and that these relations changed throughout
      the perturbation period. In addition, f and V(T) did not change necessarily in
      phase with each other. It is concluded that neither the oscillation in T(b) nor
      that in metabolism can be considered the direct cause of the daily oscillation of
      breathing. Presumably, the circadian pattern of breathing reflects the interplay
      of the daily patterns of many variables, none acting as the primary guide of the
      breathing daily rhythm.

PMID- 16815761
TI  - A simple and rapid liquid chromatography method for simultaneous determination of
      zidovudine and nevirapine in plasma.
AB  - We describe a simple, fast, isocratic, reversed-phase high performance liquid
      chromatographic method for simultaneous determination of plasma zidovudine and
      nevirapine with UV detection at 260 nm. The method involves liquid-liquid
      extraction with ethyl acetate and using 3-isobutyl 1-methyl xanthine as internal
      standard. The system requires a C(18) column (150 mm x 4.6 mm I.D.) and a mobile
      phase composed of potassium dihydrogen phosphate (15 mM; pH 7.5) and acetonitrile
      in the ratio of 80:20 (v/v). The assay was linear from 0.025 to 10.0 microg/ml
      for zidovudine and 0.05 to 10.0 microg/ml for nevirapine. The intra- and inter
      day variations were less than 10% for both the drugs. The method was specific and
      sensitive enough to allow quantification of zidovudine and nevirapine in
      concentrations observed clinically. The average recoveries of zidovudine and
      nevirapine from plasma were 95 and 94%, respectively. The method was applied to a
      pharmacokinetic study in HIV-infected patients who were receiving antiretroviral
      treatment with zidovudine and nevirapine containing regimens. The method spans
      the blood concentration range of clinical interest. Due to its simplicity, the
      assay can be used for pharmacokinetic studies and therapeutic drug monitoring in
      patients taking a combination treatment of zidovudine and nevirapine.

PMID- 16815762
TI  - Investigation of high-throughput ultrafiltration for the determination of an
      unbound compound in human plasma using liquid chromatography and tandem mass
      spectrometry with electrospray ionization.
AB  - A high-throughput ultrafiltration method with a direct injection assay has been
      developed to determine unbound concentrations of a high-protein binding compound,
      an alpha(v)beta(3) bone integrin antagonist (I), in human plasma for a clinical
      pharmacokinetic study. The 96-well MultiScreen filter plate with Ultracel-PPB
      membrane was evaluated for the separation of unbound from protein-bound compound
      I by ultrafiltration. The sample preparation was automated using a Packard
      MultiPROBE II EX liquid handling system to transfer the plasma samples to the 96
      well PPB plate for centrifugation and to prepare ultrafiltrate samples for
      analysis. Using on-line extraction with a column-switching setup for sample clean
      up and separation, the ultrafiltrate samples were directly injected onto a
      reversed-phase HPLC system and analyzed using a mass spectrometer interfaced with
      an electrospray ionization (ESI) source in the positive ionization mode (LC/ESI
      MS/MS). The performance of the ultrafiltration using Ultracel-PPB 96-well plate
      for unbound I analysis was evaluated and optimized with respect to sample volume,
      centrifugation temperature, speed and time, and the relationship of the well
      positions of the PPB plate versus filtrate volumes and concentrations. The assay
      intraday accuracy and precision were between 93.9 and 104.8 and <7.3% (CV),
      respectively. The linear range of the calibration curve for the assay was 0.1-500
      ng/mL on a Finnigan TSQ Quantum LC/ESI-MS/MS system. Evaluation and validation of
      the unbound plasma assay demonstrated it to be rapid, sensitive and reproducible.

PMID- 16815763
TI  - Utilisation of controlled pore topology for the separation of bioparticles in a
      mixed-glass beads column.
AB  - To study the flow of shaped particles in porous media, elution of spherical and
      rod-like micro-organisms was performed through beds of spherical glass beads. A
      0.04 cm/s constant flow rate was used with 5 microm yeast suspensions, 1 microm
      latex micro-spheres and rod-like bacilli Lactobacillus bulgaricus 6 microm long
      and 0.5 microm in diameter. Yeast cells' diameter is close to the bacilli length
      and micro-spheres have the same diameter as bacilli. All particle types have
      similar density. To make the different packing beds, 1.125 mm coarse beads and
      0.1115 mm fine beads were used. Experiments were carried out using a column
      loaded with the binary packing (volume fraction of coarse particles in the
      mixture 0.7) or a monosize packing with the same amount of coarse or fine
      particles as used in the binary packing. Analysis of experimental results was
      based on two models: pure exclusion effect and hydrodynamic separation model
      [hydrodynamic chromatography (HDC)]. Results for spheres show that the classic
      HDC model fits to the experimental data whenever the ratio of particle size to
      the pathway bend scale is high ( approximately 1/100, micro-spheres). However, if
      this ratio increases and becomes approximately 1/20, the HDC model needs to be
      corrected due to the effect of channel wall curvature on exclusion. This led to a
      modified HDC equation of the form R=B/(1+2lambda-2.8lambda(2)), where R is the
      retention, lambda is the aspect ratio and constant B>or=1. Bacillus separation
      follows an exclusion mechanism, since pore topology is important in the
      separation of shaped particles when the aspect ratio approaches lambda=0.1. In
      the case of a binary packing bed, rod-like particles display a different
      behaviour than the one exhibited by the spherical particles of the same scale as
      bacilli, either in length or in diameter. This may be explained by the
      interaction between rod-like bacilli and the bed's pore topology. A generalised
      exclusion model for particles was proposed to be R=A/(1-lambda)(z), where A is
      the coefficient proportional to the tortuosity and the parameter z=1, 2 or 3
      depends mainly on pore shape. Controlled pore topology opens interesting
      applications for bio-separation (in porous micro-fluidic devices, deep bed
      filtration) and might be especially important for macromolecules and micro
      organisms separation with different shapes.

PMID- 16815764
TI  - Development of an analytical method for organotin compounds in fortified flour
      samples using microwave-assisted extraction and normal-phase HPLC with UV
      detection.
AB  - The normal high-performance liquid chromatography with UV detection was applied
      for the determination of tributyltin chloride (TBT), triphenyltin chloride
      (TPhT), tetraphenyltin (TrPhT), triethyltin chloride (TET) and tetraethyltin
      (TrET) from flour samples. The separation was performed in the isocratic mode on
      cyanopropyl column with a mobile phase of hexane-acetonitrile-THF (97/1/2). Under
      the experimental conditions used, quantitative limit of TBT, TPhT, TrPhT, TET and
      TrET are 0.95, 0.46, 0.97, 0.75 and 0.96 microg/ml, respectively. Microwave
      assisted extraction of organotin (OT) compounds at 100 degrees C with an
      extraction time of 3 min was described. The extraction of organotin can be
      finished in acetic acid-hexane (20/80) medium. The quantitative extraction of
      five organotin compounds was achieved with recoveries ranging from 88 to 101%
      R.S.D. 3-8%.

PMID- 16815765
TI  - Clinical characteristics of coeliac disease (CD) in the Maltese Islands.

PMID- 16815766
TI  - Elucidation of chiral recognition processes of macrocyclic antibiotic vancomycin.
AB  - A theoretical investigation was carried out on the retention and separation of
      enantiomeric molecules including nonsteroidal anti-inflammatory drugs, anti
      neoplastic compounds and N-derivatized amino acids by capillary electrophoresis
      using macrocyclic antibiotics, a new class of chiral selectors, as stationary
      phase. Firstly docking methods were used to study the enantiorecognition in
      chiral electrophoresis. The molecular dynamics simulations of the two
      diastereoisomer complexes were then performed in order to understand how these
      antibiotics recognize the enantiomers. Another approach was applied in this study
      to establish a quantitative structure-enantioselectivity relationship (QSER)
      model, able to describe the resolution of a series of chiral compounds in
      capillary electrophoresis using vancomycin as the resolving agent.

PMID- 16815767
TI  - Validation of counter propagation neural network models for predictive toxicology
      according to the OECD principles: a case study.
AB  - The OECD has proposed five principles for validation of QSAR models used for
      regulatory purposes. Here we present a case study investigating how these
      principles can be applied to models based on Kohonen and counter propagation
      neural networks. The study is based on a counter propagation network model that
      has been built using toxicity data in fish fathead minnow for 541 compounds. The
      study demonstrates that most, if not all, of the OECD criteria may be met when
      modeling using this neural network approach.

PMID- 16815768
TI  - Physicochemical properties/descriptors governing the solubility and partitioning
      of chemicals in water-solvent-gas systems. Part 1. Partitioning between octanol
      and air.
AB  - QSPR analyses of a data set containing experimental partition coefficients in the
      three systems octanol-water, water-gas, and octanol-gas for 98 chemicals have
      shown that it is possible to calculate any partition coefficient in the system
      'gas phase/octanol/water' by three different approaches: (1) from experimental
      partition coefficients obtained in the corresponding two other subsystems.
      However, in many cases these data may not be available. Therefore, a solution may
      be approached (2), a traditional QSPR analysis based on e.g. HYBOT descriptors
      (hydrogen bond acceptor and donor factors, SigmaCa and SigmaCd, together with
      polarisability alpha, a steric bulk effect descriptor) and supplemented with
      substructural indicator variables. (3) A very promising approach which is a
      combination of the similarity concept and QSPR based on HYBOT descriptors. In
      this approach observed partition coefficients of structurally nearest neighbours
      of a compound-of-interest are used. In addition, contributions arising from
      differences in alpha, SigmaCa, and SigmaCd values between the compound-of
      interest and its nearest neighbour(s), respectively, are considered. In this
      investigation highly significant relationships were obtained by approaches (1)
      and (3) for the octanol/gas phase partition coefficient (log Log).

PMID- 16815769
TI  - A 3D-QSAR CoMSIA study on 3-azolylmethylindoles as anti-leishmanial agents.
AB  - A three-dimensional quantitative structure-activity relationship (3D-QSAR) study
      using Comparative Molecular Similarity Indices Analysis (CoMSIA) was conducted on
      a series of 3-azolylmethylindoles as anti-leishmanial agents. Evaluation of 24
      compounds synthesized in our laboratory served to establish the model. A random
      search was performed on the library of compounds, and molecules of the training
      set were aligned on common elements of template molecule 13, one of the most
      active compounds. The best predictions were obtained from multifit procedure with
      a CoMSIA model combining steric, electrostatic, hydrophobic and hydrogen bond
      acceptor fields (q2 = 0.594, r2 = 0.897). The model was validated using an
      external test set of 7 compounds giving a satisfactory predictive r2 value of
      0.649. Information obtained from CoMSIA contour maps could be used for further
      design of more promising inhibitors.

PMID- 16815770
TI  - A model validation and consensus building environment.
AB  - Over half of the failures in drug development are due to problems with the
      absorption, distribution, metabolism, excretion, and toxicity, or ADME/Tox
      properties of a candidate compound. The utilization of in silico tools to predict
      ADME/Tox and physicochemical properties holds great potential for reducing the
      attrition rate in drug research and development, as this technology can
      prioritize candidate compounds in the pharmaceutical R&D pipeline. However, a
      major concern surrounding the use of in silico ADME/Tox technology is the
      reliability of the property predictions. Bio-Rad Laboratories, Inc. has created a
      computational environment that addresses these concerns. This environment is
      referred to as KnowItAll. Within this platform are encoded a number of ADME/Tox
      predictors, the ability to validate these predictors with/without in-house data
      and models, as well as build a 'consensus' model that may be a much better model
      than any of the individual predictive model. The KnowItAll system can handle two
      types of predictions: real number and categorical classification.

PMID- 16815771
TI  - Alkane isomers: presence in petroleum ether and complexity.
AB  - The presence and absence of alkane isomers in petroleum and petroleum derivatives
      depend on the complexity of these structures. It was assumed that the more
      complex the structure is the less probable it is that that the molecule can be
      detected in any petroleum derivative. Complexity is a vague concept, which has
      not been defined in quantitative terms yet, and therefore there is no
      experimental method, which could be used to determine 'complexity'. Mass
      spectrometry and infrared spectroscopy in combination with gas chromatography
      were used to identify the various structural isomers of alkanes in petroleum
      ether. The isomers were categorised in quantitative terms by using topological
      indices and linear discriminant analysis. It was found that alkanes possessing a
      more complex, highly branched structure are less probable to be detected in
      petroleum ether than isomers with a simpler backbone structure. It was proposed
      that the experimental 'measure' of the complexity of isomer(i) should be
      proportional to 1/C(i), where C(i), denotes the concentration of isomer(i) in a
      (primary) petroleum derivative.

PMID- 16815773
TI  - Talent identification and coaching in the Journal of Sports Sciences.

PMID- 16815772
TI  - Decision threshold adjustment in class prediction.
AB  - Standard classification algorithms are generally designed to maximize the number
      of correct predictions (concordance). The criterion of maximizing the concordance
      may not be appropriate in certain applications. In practice, some applications
      may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may
      emphasize high specificity (e.g., epidemiology screening studies). This paper
      considers effects of the decision threshold on sensitivity, specificity, and
      concordance for four classification methods: logistic regression, classification
      tree, Fisher's linear discriminant analysis, and a weighted k-nearest neighbor.
      We investigated the use of decision threshold adjustment to improve performance
      of either sensitivity or specificity of a classifier under specific conditions.
      We conducted a Monte Carlo simulation showing that as the decision threshold
      increases, the sensitivity decreases and the specificity increases; but, the
      concordance values in an interval around the maximum concordance are similar. For
      specified sensitivity and specificity levels, an optimal decision threshold might
      be determined in an interval around the maximum concordance that meets the
      specified requirement. Three example data sets were analyzed for illustrations.

PMID- 16815774
TI  - The effects of fatigue on decision making and shooting skill performance in water
      polo players.
AB  - The aim of this study was to assess the effects of fatigue on decision making and
      goal shooting skill in water polo. Fourteen junior elite male players (age 17.2
      +/- 0.5 years; mass 84.2 +/- 7.6 kg; height 1.85 +/- 0.05 m) completed four sets
      of eight repetitions of an approximately 18 s maximal water polo specific drill.
      Progressively declining rest ratios for each successive set of the drill were
      employed to induce increasing fatigue and reflect the demands of match-play. A
      video-based temporally occluded decision-making task (verbalized response to
      various tactical situations) or goal shooting skill test (qualitative and
      quantitative analysis of goal shooting) was performed after each set. Heart rate,
      rating of perceived exertion (RPE) and blood lactate concentration were recorded.
      Heart rate (159 +/- 12, 168 +/- 13, 176 +/- 12, 181 +/- 12 Deats min-1; P <
      0.001) and RPE (13.1 +/- 2.2, 15.5 +/- 1.7, 17.3 +/- 1.6, 19.1 +/- 1.1; P <
      0.001) increased with declining rest ratios. At very high fatigue, decision
      making accuracy was 18.0 +/- 21.8% better than at low fatigue (P = 0.008).
      Shooting accuracy and velocity were unaffected by incremental fatigue; however,
      skill proficiency (technique) decreased by 43 +/- 24% between the pre-test and
      high-fatigue conditions (P < 0.001). In conclusion, incremental increases in
      fatigue differentially influenced decision making (improved) relative to the
      technical performance (declined), accuracy and speed of the ball (unchanged) of a
      water polo goal shot.

PMID- 16815775
TI  - Differences in fatigability between the sexes during a sustained submaximal
      contraction protocol in prepubertal children.
AB  - The aim of this study was to determine whether there are differences in the
      fatigability of plantar flexor muscles during sustained submaximal contractions
      in prepubertal boys and girls. Fifteen boys (age 10.0 +/- 1.0 years) and 15 girls
      (age 9.8 +/- 0.9 years) participated in the study. The fatigue protocol consisted
      of a 10 min isometric plantar flexion at 20% of the maximal voluntary
      contraction. Immediately after this, five maximal isometric contractions were
      performed with a 3 min interval between contractions. During the experiment,
      electromyograms of the agonist muscles soleus and medial gastrocnemius and
      antagonist tibialis anterior were recorded. We observed no differences between
      the sexes (P < 0.05) in the decrease in torque or in the recovery rate after the
      fatigue protocol. Nor were there any differences between the sexes (P < 0.05) in
      agonist or antagonist muscle activation during the fatigue protocol and recovery
      period. The results indicate that there are no differences in fatigability
      between prepubertal boys and girls during submaximal sustained contractions,
      probably because the agonist and antagonist muscles were activated similarly in
      both sexes.

PMID- 16815776
TI  - Residual volume on land and when immersed in water: effect on percent body fat.
AB  - There is a large residual volume (RV) error when assessing percent body fat by
      means of hydrostatic weighing. It has generally been measured before hydrostatic
      weighing. However, an individual's maximal exhalations on land and in the water
      may not be identical. The aims of this study were to compare residual volumes and
      vital capacities on land and when immersed to the neck in water, and to examine
      the influence of the measurement error on percent body fat. The participants were
      20 healthy Japanese males and 20 healthy Japanese females. To assess the
      influence of the RV error on percent body fat in both conditions and to evaluate
      the cross-validity of the prediction equation, another 20 males and 20 females
      were measured using hydrostatic weighing. Residual volume was measured on land
      and in the water using a nitrogen wash-out technique based on an open-circuit
      approach. In water, residual volume was measured with the participant sitting on
      a chair while the whole body, except the head, was submerged . The trial-to-trial
      reliabilities of residual volume in both conditions were very good (intraclass
      correlation coefficient > 0.98). Although residual volume measured under the two
      conditions did not agree completely, they showed a high correlation (males:
      0.880; females: 0.853; P < 0.05). The limits of agreement for residual volumes in
      both conditions using Bland-Altman plots were -0.430 to 0.508 litres. This range
      was larger than the trial-to-trial error of residual volume on land (-0.260 to
      0.304 litres). Moreover, the relationship between percent body fat computed using
      residual volume measured in both conditions was very good for both sexes (males:
      r = 0.902; females: r = 0.869, P < 0.0001), and the errors were approximately -6
      to 4% (limits of agreement for percent body fat: -3.4 to 2.2% for males; -6.3 to
      4.4% for females). We conclude that if these errors are of no importance,
      residual volume measured on land can be used when assessing body composition.

PMID- 16815777
TI  - Effect of aqua exercise on recovery of lower limb muscles after downhill running.
AB  - The aim of the present study was to examine how the recovery of physiological
      functioning of the leg muscles after high-intensity eccentric exercise such as
      downhill running could be promoted by aqua exercise for a period until the
      damaged muscle had recovered almost completely. Ten male long-distance runners
      were divided equally into an aqua exercise group and a control group. From the
      first day (Day 0) to the fourth day (Day 3), the participants completed a
      questionnaire on muscle soreness, and serum creatine kinase activity, muscle
      power, flexibility, whole-body reaction time and muscle stiffness were measured.
      After measurements on Day 0, the participants performed downhill running (three 5
      min runs with a 5 min rest interval at -10%, 335.7 +/- 6.1 m . min-1). The aqua
      exercise group performed walking, jogging and jumping in water on three
      successive days following the downhill running on Day 0 for 30 min each day.
      Muscle power was reduced on Day 1 in the control group (P < 0.05). Muscle
      soreness in the calf on Day 3 was greater in the control group than that in the
      aqua exercise group (P < 0.05). In the aqua exercise group, muscle stiffness in
      the calf was less than that in the control group over 4 days (time main effect: P
      < 0.05; group x time interaction: P < 0.05). We conclude that aqua exercise
      promoted physiological functioning of the muscles in the legs after high
      intensity downhill running for a period until the damaged muscles had recovered
      almost completely.

PMID- 16815778
TI  - The effects of impact and non-impact exercise on circulating markers of collagen
      remodelling in humans.
AB  - Exercise has been shown to influence collagen synthesis and degradation. The aim
      of this study was to determine whether the stimulus for these changes is
      metabolic or mechanical. Eight healthy adults aged 22 +/- 4 years (mean +/- s)
      completed two exercise bouts-a 10 km road run and a deep water running session.
      Blood samples were collected before exercise and on days 1, 2, 3, 6 and 10 after
      exercise for measurement of creatine kinase activity, type IV collagen
      antigenicity, and concentrations of matrix metalloproteinase (MMP)- 9, tissue
      inhibitors of metalloproteinase (TIMP)- 1 and -2, and the MMP-2/TIMP-2 complex.
      Serum creatine kinase was elevated 24 h after the road run, but unchanged after
      the deep water running session. Serum collagen IV antigenicity decreased after
      both the road run and the deep water running session, suggesting suppressed type
      IV collagen synthesis in response to exercise, although serum MMPs and TIMPs
      remained unchanged after exercise. These results suggest that collagen IV
      synthesis is temporarily suppressed after exercise, irrespective of exercise
      type.

PMID- 16815779
TI  - The angiogenetic effect of intramuscular administration of b-FGF and a-FGF on
      cardiac muscle: the influence of exercise on muscle angiogenesis.
AB  - Although angiogenetic therapy using recombinant growth factors holds much hope
      for the treatment of ischaemic diseases, there are still many unanswered
      questions, including the method of administration, the correct dose of these
      factors, and the duration of the therapeutic approach. Exercise has also been
      suggested to induce neovascularizaiton in muscles. We evaluated the angiogenetic
      effects of the intramuscular administration of basic-fibroblast growth factor (b
      FGF) and acidic-fibroblast growth factor (a-FGF) in rat heart, compared with rats
      who exercised daily. In conclusion, both the intramuscular administration of b
      FGF and exercise increased significantly angiogenesis in the heart in contrast to
      the intramuscular administration of a-FGF, which was ineffective.

PMID- 16815780
TI  - Individual differences in the interleukin-6 response to maximal and submaximal
      exercise tasks.
AB  - The inflammatory responsive cytokine interleukin-6 (IL-6) helps regulate immune
      responses to exercise. Evidence suggests that increases in IL-6 are related to
      exercise duration and intensity. However, the moderating effect of sex and
      underlying mediators have received limited attention. We compared plasma IL-6
      responses to two cycling tasks with a resting control in young male (n = 12) and
      female (n = 12) recreationally active adults. Both 45 min tasks comprised an
      incremental test, either maximal or submaximal, followed by steady-state exercise
      at 55% peak power output. Interleukin-6 was elevated above baseline immediately
      after the maximal but not the submaximal task. Compared with the control
      condition, IL-6 was increased at 30 and 60 min after both exercise tasks. The IL
      6 response was greater in women than men at 60 min after maximal exercise.
      Cortisol increased in both tasks compared with the control condition, the
      increase being greater after maximal than submaximal exercise. No associations
      were found between IL-6 responses and cortisol, heart rate, fitness or body mass
      index. The results show that 45 min of moderate-intensity exercise can increase
      IL-6 and suggest that the inclusion of maximal effort may accelerate this
      response. The finding that women showed a greater IL-6 response to maximal
      exercise may reflect a gender dimorphism in the immune response to stress.

PMID- 16815781
TI  - Agreement between polar and SRM mobile ergometer systems during laboratory-based
      high-intensity, intermittent cycling activity.
AB  - The purpose of this study was to assess the agreement between two mobile cycle
      ergometer systems for recording high-intensity, intermittent power output. Twelve
      trained male cyclists (age 31.4 +/- 9.8 years) performed a single 3 min
      intermittent cycle test consisting of 12 all-out efforts, separated by periods of
      passive recovery ranging from 5 to 15 s. Power output was recorded using a Polar
      S710 heart rate monitor and power sensor kit and an SRM Powercrank system for
      each test. The SRM used torque and angular velocity to calculate power, while the
      S710 used chain speed and vibration to calculate power. Significant differences
      (P < 0.05) in power were found at 8 of the 12 efforts. A significant difference
      (P = 0.001) was also found when power was averaged over all 12 intervals. Mean
      power was 556 +/- 102 W and 446 +/- 61 W for the SRM and S710 respectively. The
      S710 underestimated power by an average of 23% with random errors of */[division
      sign] 24% when compared with the SRM. Random errors ranged from 36% to 141% with
      a median of 51%. The results indicate there was little agreement between the two
      systems and that the Polar S710 did not provide a valid measure of power during
      intermittent cycling activity when compared with the SRM. Power recorded by the
      S710 system was influenced greatly by chain vibration and sampling rates.

PMID- 16815782
TI  - Assessment of hydration status by urinary analysis of elite junior taekwon-do
      athletes in preparing for competition.
AB  - The aim of this study was to assess over time the hydration status of taekwon-do
      athletes during a preparatory camp. Measures of urine osmolality, conductivity,
      specific gravity and colour were made on the first urine sample passed by the
      participants (n = 32) in the morning before breakfast. The urinary measurements
      were made on samples collected at the beginning of the camp, 5 days later and one
      day before competition. Body mass was also measured at the same instants. Body
      mass (mean +/- s) was essentially the same on each of the measurement days (62.6
      +/- 12.2, 62.7 +/- 12.3 and 62.2 +/- 12.6 kg, respectively). Mean urine
      osmolality at the beginning of the camp was relatively high (998 +/- 171 mOsmol .
      kg-1), suggesting that a significant number of the athletes were already
      hypohydrated. However, no significant differences were detected in urine
      osmolality at the three time points during the study. There were no significant
      differences in any of the four methods of urine analysis during the study (P >
      0.05). The average values for all samples were 989 +/- 205 mOsmol . kg-1 for
      osmolality, 25.5 +/- 6.7 mS . cm-1 for conductivity, 1.017 +/- 0.010 g . cm-3 for
      specific gravity and 4 +/- 1 arbitrary units for colour. Correlation analysis
      between the different methods suggested moderately good agreement (correlation
      coefficient = 0.5-0.7) between all four measurement techniques (P < 0.01). The
      coefficients of variation for these techniques were relatively low (CV = 11.8 -
      35.0%). The results of this study suggest that some of the taekwon-do athletes
      were slightly hypohydrated in the morning on each of the test days, but there was
      no evidence to suggest that most of the athletes further restricted their fluid
      intake to make weight. In addition, it appears that each of the four methods used
      gave essentially the same estimate of hydration status of these athletes.

PMID- 16815783
TI  - Influence of caffeine on perception of effort, metabolism and exercise
      performance following a high-fat meal.
AB  - This study examined the effects of caffeine, co-ingested with a high fat meal, on
      perceptual and metabolic responses during incremental (Experiment 1) and
      endurance (Experiment 2) exercise performance. Trained participants performed
      three constant-load cycling tests at approximately 73% of maximal oxygen uptake
      (VO2max) for 30 min at 20 degrees C (Experiment 1, n = 8) and to the limit of
      tolerance at 10 degrees C (Experiment 2, n = 10). The 30 min constant-load
      exercise in Experiment 1 was followed by incremental exercise (15 W . min-1) to
      fatigue. Four hours before the first test, the participants consumed a 90%
      carbohydrate meal (control trial); in the remaining two tests, the participants
      consumed a 90% fat meal with (fat + caffeine trial) and without (fat-only trial)
      caffeine. Caffeine and placebo were randomly assigned and ingested 1 h before
      exercise. In both experiments, ratings of perceived leg exertion were
      significantly lower during the fat + caffeine than fat-only trial (Experiment 1:
      P < 0.001; Experiment 2: P < 0.01). Ratings of perceived breathlessness were
      significantly lower in Experiment 1 (P < 0.01) and heart rate higher in
      Experiment 2 (P < 0.001) on the fat + caffeine than fat-only trial. In the two
      experiments, oxygen uptake, ventilation, blood [glucose], [lactate] and plasma
      [glycerol] were significantly higher on the fat + caffeine than fat-only trial.
      In Experiment 2, plasma [free fatty acids], blood [pyruvate] and the
      [lactate]:[pyruvate] ratio were significantly higher on the fat + caffeine than
      fat-only trial. Time to exhaustion during incremental exercise (Experiment 1:
      control: 4.9, s = 1.8 min; fat-only: 5.0, s = 2.2 min; fat + caffeine: 5.0, s =
      2.2 min; P > 0.05) and constant-load exercise (Experiment 2: control: 116 (88 -
      145) min; fat-only: 122 (96 - 144) min; fat + caffeine: 127 (107 - 176) min; P >
      0.05) was not different between the fat-only and fat + caffeine trials. In
      conclusion, while a number of metabolic responses were increased during exercise
      after caffeine ingestion, perception of effort was reduced and this may be
      attributed to the direct stimulatory effect of caffeine on the central nervous
      system. However, this caffeine-induced reduction in effort perception did not
      improve exercise performance.

PMID- 16815784
TI  - Changes in long jump take-off technique with increasing run-up speed.
AB  - The aim of this study was to determine the influence of run-up speed on take-off
      technique in the long jump. Seventy-one jumps by an elite male long jumper were
      recorded in the sagittal plane by a high-speed video camera. A wide range of run
      up speeds was obtained using direct intervention to set the length of the
      athlete's run-up. As the athlete's run-up speed increased, the jump distance and
      take-off speed increased, the leg angle at touchdown remained almost unchanged,
      and the take-off angle and take-off duration steadily decreased. The predictions
      of two previously published mathematical models of the long jump take-off are in
      reasonable agreement with the experimental data.

PMID- 16815785
TI  - Redesign and initial validation of an instrument to assess the motivational
      qualities of music in exercise: the Brunel Music Rating Inventory-2.
AB  - In the present study, a measure to assess the motivational qualities of music in
      exercise was redesigned, extending previous research efforts (Karageorghis et
      al., 1999). The original measure, the Brunel Music Rating Inventory (BMRI), had
      shown limitations in its factor structure and its applicability to non-experts in
      music selection. Redesign of the BMRI used in-depth interviews with eight
      participants (mean age 31.9 years, s = 8.9 years) to establish the initial item
      pool, which was examined using a series of confirmatory factor analyses. A single
      factor model provided a good fit across three musical selections with different
      motivational qualities (comparative fit index, CFI: 0.95-0.98; standardized root
      mean residual, SRMR: 0.03-0.05). The single-factor model also demonstrated
      acceptable fit across two independent samples and both sexes using one piece of
      music (CFI: 0.86-1.00; SRMR: 0.04-0.07). The BMRI was designed for experts in
      selecting music for exercise (e.g. dance aerobic instructors), whereas the BMRI-2
      can be used both by exercise instructors and participants. The psychometric
      properties of the BMRI-2 are stronger than those of the BMRI and it is easier to
      use. The BMRI-2 provides a valid and internally consistent tool by which music
      can be selected to accompany a bout of exercise or a training session.
      Furthermore, the BMRI-2 enables researchers to standardize music in experimental
      protocols involving exercise-related tasks.

PMID- 16815786
TI  - Cytokine responses to resistance training in people with multiple sclerosis.
AB  - Exercise for individuals with multiple sclerosis (MS) has been shown to improve
      cardiovascular function, increase strength and endurance, and reduce fatigue. The
      impact of exercise on immune function in the disease, however, remains mostly
      unexplored. Ten female MS patients participated in an 8 week programme of twice
      weekly progressive resistance training, with pre- and post-training assessment of
      serum concentrations of cytokines IL-2, IL-4, IL-6, IL-10, CRP, TNF-alpha and IFN
      gamma. After training, IL-4, IL-10, CRP and IFN-gamma showed statistically
      reduced resting concentrations in blood, while TNF-alpha showed non-significant
      reductions and IL-2 and IL-6 remained unchanged. These results suggest that
      progressive resistance training may have an impact on cytokine concentrations in
      individuals with MS and should be confirmed in studies with stronger statistical
      power. The impact of these changes on overall immune function in MS and on
      disease status and prognosis remains to be determined.

PMID- 16815787
TI  - Functional communication and executive function in aphasia.
AB  - The purpose of this exploratory study was to investigate the relationship between
      functional communication and executive function ability in aphasia. Twenty-five
      participants with aphasia underwent examination with an extensive test battery
      including measures of functional communication, executive function ability, and
      language impairment. Compared to published norms, most participants did not
      perform within normal limits on the executive function tests. As expected, the
      correlation between severity of language impairment and functional communication
      ratings exceeded that among the executive functioning and functional
      communication measures. Eight of ten correlation coefficients for the
      relationship between executive functioning and functional communication reached
      statistical significance suggesting a clear relationship between scores on the
      executive functioning measures and functional communication ability. Based on
      these results, it appears that decreased executive functioning ability may
      coincide with decreased functional communication ability in persons with aphasia.

PMID- 16815788
TI  - Error consistency and the evaluation of treatment outcomes.
AB  - The consistency/variability of error substitution patterns may hold important
      implications for subgrouping children with speech disorders, as well as for
      relationships between learning and generalization patterns. There is a need to
      quantify and examine the range of consistency/variability within the speech
      disordered population as it relates to system-wide change. This investigation
      compared two groups of preschool children (N = 10 each) differing in the
      consistency/variability of errors on a variety of pre-treatment and treatment
      outcome measures. The Error Consistency Index (ECI), a measure of error
      variability across the entire phonological system, was used to identify groups at
      the extreme ends of the ECI distribution from a larger participant pool. Each
      participant was treated on three target singletons from among obstruents /s, z,
      f, integral, tintegral, k, g/ and liquids /l, r/ and change on these targets, as
      well as their generalization to untrained positions was assessed. Although there
      were significant differences between the variable and consistent groups on all
      pre-treatment measures, there were no significant group differences in target and
      generalization learning or in per cent consonants correct (PCC) change. These
      findings provide evidence to suggest that relationships observed between error
      variability for individual phonemes and learning of those targets may differ from
      those observed when consistency/variability is quantified for the entire system
      and change across a number of phonemes, and the system as a whole, is examined.

PMID- 16815789
TI  - Characteristics of the sound systems of monolingual Vietnamese-speaking children
      with phonological impairment.
AB  - There has been little or no research on Vietnamese phonological development, let
      alone on phonological disorders of Vietnamese-speaking children. The goal of this
      study is to evaluate the sound systems of monolingual Vietnamese-speaking
      children with phonological impairment. Independent and relational analyses of
      four children (ages 4;4 to 5;5) are presented in terms of error patterns,
      dialectal patterns, phonotactic constraints, and phonetic and phonemic
      inventories. The characteristics of these children's sound systems are compared
      to studies of phonological acquisition of other languages, in order to identify
      characteristics that may be universal versus those that may be language-specific
      in nature.

PMID- 16815790
TI  - A study of humour and communicative intention following right hemisphere stroke.
AB  - This research provides further data regarding non-literal language comprehension
      following right hemisphere damage (RHD). To assess the impact of RHD on the
      processing of non-literal language, ten participants presenting with RHD and ten
      matched healthy control participants were administered tasks tapping humour
      appreciation and pragmatic interpretation of non-literal language. Although the
      RHD participants exhibited a relatively intact ability to interpret humour from
      jokes, their use of pragmatic knowledge about interpersonal relationships in
      discourse was significantly reduced, leading to abnormalities in their
      understanding of communicative intentions (CI). Results imply that explicitly
      detailing CI in discourse facilitates RHD participants' comprehension of non
      literal language.

PMID- 16815791
TI  - Acoustic and perceptual analysis of modal and falsetto registers in females with
      dysphonia.
AB  - Modal and falsetto registers are the basic vocal qualities used in female
      speaking voices. The purpose of this study was to identify the frequency at which
      modal register changed to falsetto register and the frequency range of each modal
      and falsetto register produced under three loudness levels: soft, comfortable and
      loud phonations in normal and dysphonic speakers. These data provide information
      on the relationship between vocal registers. It is hypothesized that vocal
      pathologies affect the frequency at which register change from one mode to
      another mode. Fifteen dysphonic and 15 non-dysphonic females were assessed on
      their ability to produce tone series from the lowest to the highest frequency at
      soft, comfortable and loud phonations. Fourteen listeners served as judges to
      identify the first production of falsetto voice in each tone series. The first
      falsetto tone perceived was considered to represent the frequency at which the
      modal-falsetto register change occurred perceptually. The change from modal to
      falsetto register in the tone series occurred between G4 (360.74 Hz) and B4
      (485.23 Hz) in the dysphonic group and between A4 (421.00 Hz) and B4 (476.13 Hz)
      in the non-dysphonic group among the three loudness levels. The results showed
      that the presence of dysphonia affected the production of vocal registers The
      dysphonic group demonstrated the modal-falsetto register change at a
      significantly lower frequency and reduced frequency range in the modal register
      than those of the non-dysphonic group in the soft and comfortable phonations. In
      producing falsetto register, the dysphonic group demonstrated reduced ability in
      producing falsetto register in soft and loud phonations when compared to the non
      dysphonic group. Physiological explanations are used to account for the
      observations.

PMID- 16815793
TI  - Introduction to the reviews on appetite.

PMID- 16815794
TI  - Genetics of obesity.
AB  - Considerable attention is currently being paid to the secular changes in food
      intake and physical activity that underlie the increase in the prevalence of
      obesity that is apparent in many societies. While this is laudable it would be
      unwise to view these environmental factors in isolation from the biological
      factors that normally control body weight and composition and the compelling
      evidence that inter-individual differences in susceptibility to obesity have
      strong genetic determinants. This is particularly important, as it is only in the
      past decade that we have begun to obtain substantive information regarding the
      molecular constituents of pathways controlling mammalian energy balance and
      therefore, for the first time, are in a position to achieve a better mechanistic
      understanding of this disease. Population-based association and linkage studies
      have highlighted a number of loci at which genetic variation is associated with
      obesity and related phenotypes and the identification and characterization of
      monogenic obesity syndromes has been particularly fruitful. While there is
      widespread acceptance that hereditary factors might predispose to human obesity,
      it is frequently assumed that such factors would influence metabolic rate or the
      selective partitioning of excess calories into fat. However, it is notable that,
      thus far, all monogenic defects causing human obesity actually disrupt
      hypothalamic pathways and have a profound effect on satiety and food intake. To
      conclude, the evidence we have to date suggests that the major impact of genes on
      human obesity is just as likely (or perhaps more likely) to directly impact on
      hunger, satiety and food intake rather than metabolic rate or nutrient
      partitioning. At the risk of oversimplification, it seems that from an
      aetiological/genetic standpoint, human obesity appears less a metabolic than a
      neuro-behavioural disease.

PMID- 16815796
TI  - Brain mechanisms underlying flavour and appetite.
AB  - Complementary neurophysiological recordings in macaques and functional
      neuroimaging in humans show that the primary taste cortex in the rostral insula
      and adjoining frontal operculum provides separate and combined representations of
      the taste, temperature and texture (including viscosity and fat texture) of food
      in the mouth independently of hunger and thus of reward value and pleasantness.
      One synapse on, in the orbitofrontal cortex, these sensory inputs are for some
      neurons combined by learning with olfactory and visual inputs. Different neurons
      respond to different combinations, providing a rich representation of the sensory
      properties of food. In the orbitofrontal cortex, feeding to satiety with one food
      decreases the responses of these neurons to that food, but not to other foods,
      showing that sensory-specific satiety is computed in the primate (including
      human) orbitofrontal cortex. Consistently, activation of parts of the human
      orbitofrontal cortex correlates with subjective ratings of the pleasantness of
      the taste and smell of food. Cognitive factors, such as a word label presented
      with an odour, influence the pleasantness of the odour and the activation
      produced by the odour in the orbitofrontal cortex. These findings provide a basis
      for understanding how what is in the mouth is represented by independent
      information channels in the brain; how the information from these channels is
      combined; and how and where the reward and subjective affective value of food is
      represented and is influenced by satiety signals. Activation of these
      representations in the orbitofrontal cortex may provide the goal for eating, and
      understanding them helps to provide a basis for understanding appetite and its
      disorders.

PMID- 16815795
TI  - Metabolic imprinting: critical impact of the perinatal environment on the
      regulation of energy homeostasis.
AB  - Epidemiological studies in humans suggest that maternal undernutrition, obesity
      and diabetes during gestation and lactation can all produce obesity in offspring.
      Animal models have allowed us to investigate the independent consequences of
      altering the pre- versus post-natal environments on a variety of metabolic,
      physiological and neuroendocrine functions as they effect the development in the
      offspring of obesity, diabetes, hypertension and hyperlipidemia (the 'metabolic
      syndrome'). During gestation, maternal malnutrition, obesity, type 1 and type 2
      diabetes and psychological, immunological and pharmacological stressors can all
      promote offspring obesity. Normal post-natal nutrition can reduce the adverse
      impact of some of these pre-natal factors but maternal high-fat diets, diabetes
      and increased neonatal access to food all enhance the development of obesity and
      the metabolic syndrome in offspring. The outcome of these perturbations of the
      perinatal environmental is also highly dependent upon the genetic background of
      the individual. Those with an obesity-prone genotype are more likely to be
      affected by factors such as maternal obesity and high-fat diets than are obesity
      resistant individuals. Many perinatal manipulations appear to promote offspring
      obesity by permanently altering the development of central neural pathways, which
      regulate food intake, energy expenditure and storage. Given their strong
      neurotrophic properties, either excess or an absence of insulin and leptin during
      the perinatal period are likely to be effectors of these developmental changes.
      Because obesity is associated with an increased morbidity and mortality and
      because of its resistance to treatment, prevention is likely to be the best
      strategy for stemming the tide of the obesity epidemic. Such prevention should
      begin in the perinatal period with the identification and avoidance of factors
      which produce permanent, adverse alterations in neural pathways which control
      energy homeostasis.

PMID- 16815797
TI  - Psychophysics of sweet and fat perception in obesity: problems, solutions and new
      perspectives.
AB  - Psychophysical comparisons seem to show that obese individuals experience normal
      sweet and fat sensations, they like sweetness the same or less, but like fat more
      than the non-obese do. These psychophysical comparisons have been made using
      scales (visual analogue or category) that assume intensity labels (e.g.
      extremely) which denote the same absolute perceived intensity to all. In reality,
      the perceived intensities denoted by labels vary because they depend on
      experiences with the substances to be judged. This variation makes comparisons
      invalid. Valid comparisons can be made by asking the subjects to rate their
      sensory/hedonic experiences in contexts that are not related to the specific
      experiences of interest. Using this methodology, we present the evidence that the
      sensory and hedonic properties of sweet and fat vary with body mass index. The
      obese live in different orosensory and orohedonic worlds than do the non-obese;
      the obese experience reduced sweetness, which probably intensifies fat
      sensations, and the obese like both sweet and fat more than the non-obese do.
      Genetic variation as well as taste pathology contribute to these results. These
      psychophysical advances will impact experimental as well as clinical studies of
      obesity and other eating disorders.

PMID- 16815799
TI  - Hyperphagia and obesity in OLETF rats lacking CCK-1 receptors.
AB  - The brain-gut peptide cholecystokinin (CCK) inhibits food intake following
      peripheral or site directed central administration. Peripheral exogenous CCK
      inhibits food intake by reducing the size and duration of a meal. Antagonist
      studies have demonstrated that the actions of the exogenous peptide mimic those
      of endogenous CCK. Antagonist administration results in increased meal size and
      meal duration. The feeding inhibitory actions of CCK are mediated through
      interactions with CCK-1 receptors. The recent identification of the Otsuka-Long
      Evans-Tokushima Fatty (OLETF) rat as a spontaneous CCK-1 receptor knockout model
      has allowed a more comprehensive evaluation of the feeding actions of CCK. OLETF
      rats become obese and develop non-insulin dependent diabetes mellitus (NIDDM).
      Consistent with the absence of CCK-1 receptors, OLETF rats do not respond to
      exogenous CCK. OLETF rats are hyperphagic and their increased food intake is
      characterized by a large increase in meal size with a decrease in meal frequency
      that is not sufficient to compensate for the meal size increase. Deficits in meal
      size control are evident in OLETF rats as young as 2 days of age. OLETF obesity
      is secondary to the increased food intake. Pair feeding to amounts consumed by
      intact control rats normalizes body weight, body fat and elevated insulin and
      glucose levels. Hypothalamic arcuate nucleus peptide mRNA expression in OLETF
      rats is appropriate to their obesity and is normalized by pair feeding. In
      contrast, pair fed and young pre-obese OLETF rats have greatly elevated
      dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) mRNA expression. Elevated DMH
      NPY in OLETF rats appears to be a consequence of the absence of CCK-1 receptors.
      In intact rats NPY and CCK-1 receptors colocalize to neurons within the compact
      subregion of the DMH and local CCK administration reduces food intake and
      decreases DMH NPY mRNA expression. We have proposed that the absence of DMH CCK-1
      receptors significantly contributes to the OLETF's inability to compensate for
      their meal size control deficit leading to their overall hyperphagia. Access to a
      running wheel and the resulting exercise normalizes food intake and body weight
      in OLETF rats. When given access to running wheels for 6 weeks shortly after
      weaning, OLETF rats do not gain weight to the same degree as sedentary OLETF rats
      and do not develop NIDDM. Exercise also prevents elevated levels of DMH NPY mRNA
      expression, suggesting that exercise exerts an alternative, non-CCK mediated,
      control on DMH NPY. The OLETF rat is a valuable model for characterizing actions
      of CCK in energy balance and has provided novel insights into interactions
      between exercise and food intake.

PMID- 16815798
TI  - Gastrointestinal hormones regulating appetite.
AB  - The role of gastrointestinal hormones in the regulation of appetite is reviewed.
      The gastrointestinal tract is the largest endocrine organ in the body. Gut
      hormones function to optimize the process of digestion and absorption of
      nutrients by the gut. In this capacity, their local effects on gastrointestinal
      motility and secretion have been well characterized. By altering the rate at
      which nutrients are delivered to compartments of the alimentary canal, the
      control of food intake arguably constitutes another point at which intervention
      may promote efficient digestion and nutrient uptake. In recent decades, gut
      hormones have come to occupy a central place in the complex neuroendocrine
      interactions that underlie the regulation of energy balance. Many gut peptides
      have been shown to influence energy intake. The most well studied in this regard
      are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like
      peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin,
      these hormones act to increase satiety and decrease food intake. The mechanisms
      by which gut hormones modify feeding are the subject of ongoing investigation.
      Local effects such as the inhibition of gastric emptying might contribute to the
      decrease in energy intake. Activation of mechanoreceptors as a result of gastric
      distension may inhibit further food intake via neural reflex arcs. Circulating
      gut hormones have also been shown to act directly on neurons in hypothalamic and
      brainstem centres of appetite control. The median eminence and area postrema are
      characterized by a deficiency of the blood-brain barrier. Some investigators
      argue that this renders neighbouring structures, such as the arcuate nucleus of
      the hypothalamus and the nucleus of the tractus solitarius in the brainstem,
      susceptible to influence by circulating factors. Extensive reciprocal connections
      exist between these areas and the hypothalamic paraventricular nucleus and other
      energy-regulating centres of the central nervous system. In this way, hormonal
      signals from the gut may be translated into the subjective sensation of satiety.
      Moreover, the importance of the brain-gut axis in the control of food intake is
      reflected in the dual role exhibited by many gut peptides as both hormones and
      neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons
      projecting both into and out of areas of the central nervous system critical to
      energy balance. The global increase in the incidence of obesity and the
      associated burden of morbidity has imparted greater urgency to understanding the
      processes of appetite control. Appetite regulation offers an integrated model of
      a brain-gut axis comprising both endocrine and neurological systems. As
      physiological mediators of satiety, gut hormones offer an attractive therapeutic
      target in the treatment of obesity.

PMID- 16815800
TI  - Pancreatic signals controlling food intake; insulin, glucagon and amylin.
AB  - The control of food intake and body weight by the brain relies upon the detection
      and integration of signals reflecting energy stores and fluxes, and their
      interaction with many different inputs related to food palatability and
      gastrointestinal handling as well as social, emotional, circadian, habitual and
      other situational factors. This review focuses upon the role of hormones secreted
      by the endocrine pancreas: hormones, which individually and collectively
      influence food intake, with an emphasis upon insulin, glucagon and amylin.
      Insulin and amylin are co-secreted by B-cells and provide a signal that reflects
      both circulating energy in the form of glucose and stored energy in the form of
      visceral adipose tissue. Insulin acts directly at the liver to suppress the
      synthesis and secretion of glucose, and some plasma insulin is transported into
      the brain and especially the mediobasal hypothalamus where it elicits a net
      catabolic response, particularly reduced food intake and loss of body weight.
      Amylin reduces meal size by stimulating neurons in the hindbrain, and there is
      evidence that amylin additionally functions as an adiposity signal controlling
      body weight as well as meal size. Glucagon is secreted from A-cells and increases
      glucose secretion from the liver. Glucagon acts in the liver to reduce meal size,
      the signal being relayed to the brain via the vagus nerves. To summarize,
      hormones of the endocrine pancreas are collectively at the crossroads of many
      aspects of energy homeostasis. Glucagon and amylin act in the short term to
      reduce meal size, and insulin sensitizes the brain to short-term meal-generated
      satiety signals; and insulin and perhaps amylin as well act over longer intervals
      to modulate the amount of fat maintained and defended by the brain. Hormones of
      the endocrine pancreas interact with receptors at many points along the gut-brain
      axis, from the liver to the sensory vagus nerve to the hindbrain to the
      hypothalamus; and their signals are conveyed both neurally and humorally.
      Finally, their actions include gastrointestinal and metabolic as well as
      behavioural effects.

PMID- 16815801
TI  - Appetite and energy balance signals from adipocytes.
AB  - Interest in the biology of white adipose tissue has risen markedly with the
      recent surge in obesity and its associated disorders. The tissue is no longer
      viewed simply as a vehicle for lipid storage; instead, it is recognized as a
      major endocrine and secretory organ. White adipocytes release a multiplicity of
      protein hormones, signals and factors, termed adipokines, with an extensive range
      of physiological actions. Foremost among these various adipokines is the cytokine
      like hormone, leptin, which is synthesized predominantly in white fat. Leptin
      plays a critical role in the control of appetite and energy balance, with
      mutations in the genes encoding the hormone or its receptor leading to profound
      obesity in both rodents and man. Leptin regulates appetite primarily through an
      interaction with hypothalamic neuroendocrine pathways, inhibiting orexigenic
      peptides such as neuropeptide Y and orexin A, and stimulating anorexigenic
      peptides such as proopiomelanocortin. White fat also secretes several putative
      appetite-related adipokines, which include interleukin-6 and adiponectin, but
      whether these are indeed significant signals in the regulation of food intake has
      not been established. Through leptin and the other adipokines it is evident that
      adipose tissue communicates extensively with other organs and plays a pervasive
      role in metabolic homeostasis.

PMID- 16815802
TI  - Modulation of appetite by gonadal steroid hormones.
AB  - Several sex differences in eating, their control by gonadal steroid hormones and
      their peripheral and central mediating mechanisms are reviewed. Adult female rats
      and mice as well as women eat less during the peri-ovulatory phase of the ovarian
      cycle (estrus in rats and mice) than other phases, an effect under the control of
      cyclic changes in estradiol secretion. Women also appear to eat more sweets
      during the luteal phase of the cycle than other phases, possibly due to
      simultaneous increases in estradiol and progesterone. In rats and mice,
      gonadectomy reveals further sex differences: orchiectomy decreases food intake by
      decreasing meal frequency and ovariectomy increases food intake by increasing
      meal size. These changes are reversed by testosterone and estradiol treatment,
      respectively. A variety of peripheral feedback controls of eating, including
      ghrelin, cholecystokinin (CCK), glucagon, hepatic fatty acid oxidation, insulin
      and leptin, has been shown to be estradiol-sensitive under at least some
      conditions and may mediate the estrogenic inhibition of eating. Of these, most
      progress has been made in the case of CCK. Neurons expressing estrogen receptor
      alpha in the nucleus tractus solitarius of the brainstem appear to increase their
      sensitivity to CCK-induced vagal afferent input so as to lead to an increase in
      the satiating potency of CCK, and consequently decreased food intake, during the
      peri-ovulatory period in rats. Central serotonergic mechanisms also appear to be
      part of the effect of estradiol on eating. The physiological roles of other
      peripheral feedback controls of eating and their central mediators remain to be
      established.

PMID- 16815803
TI  - The role of the central melanocortin system in the regulation of food intake and
      energy homeostasis: lessons from mouse models.
AB  - A little more than a decade ago, the molecular basis of the lipostat was largely
      unknown. At that time, many laboratories were at work attempting to clone the
      genes encoding the obesity, diabetes, fatty, tubby and agouti loci, with the hope
      that identification of these obesity genes would help shed light on the process
      of energy homeostasis, appetite and energy expenditure. Characterization of
      obesity and diabetes elucidated the nature of the adipostatic hormone leptin and
      its receptor, respectively, while cloning of the agouti gene eventually led to
      the identification and characterization of one of the key neural systems upon
      which leptin acts to regulate intake and expenditure. In this review, we describe
      the neural circuitry known as the central melanocortin system and discuss the
      current understanding of its role in feeding and other processes involved in
      energy homeostasis.

PMID- 16815805
TI  - Connecting stuttering management and measurement: I. Core speech measures of
      clinical process and outcome.
AB  - BACKGROUND: There will always be a place for stuttering treatments designed to
      eliminate or reduce stuttered speech. When those treatments are required, direct
      speech measures of treatment process and outcome are needed in clinical practice.
      AIMS: Based on the contents of published clinical trials of such treatments,
      three 'core' measures of treatment outcome are presented for consideration by
      clinicians: measures of stuttering rate, speech rate and speech naturaleness.
      MAIN CONTRIBUTION: In contrast to clinical trials, however, clinicians are at
      liberty to have as many outcome measures as thought necessary, and to design non
      standard ones to suit their needs and those of their clients. In that context,
      the merits of severity ratings of stuttering are considered. It is argued that
      the prime source of guidance of suitable measures of treatment process are the
      manuals of the treatments that have figured in clinical trials. CONCLUSIONS:
      Although there are independent data sources that contradict the axiom that
      treatment outcomes should be measured beyond the clinic, it is argued that it is
      premature to dispense with beyond-clinic process outcome measures for clinical
      practice. It is argued that for clinicians who conduct treatments in non-research
      contexts, one pretreatment outcome measurement occasion is sufficient, along with
      post-treatment measures at each maintenance visit. More than anything else, the
      numerous advantages of severity ratings of stuttering facilitate clinical
      measurement of treatment outcome and treatment process in several settings and on
      several occasions.

PMID- 16815806
TI  - Connecting stuttering measurement and management: II. Measures of cognition and
      affect.
AB  - BACKGROUND: To the person who stutters, there are other experiences than the
      somatic ones of stuttered speech. These are experiences of cognition and affect:
      in other words, experiences of thought and emotion. For several reasons, it is
      quite difficult to determine and recommend core measures of cognition and affect
      for clinicians to consider using. AIMS: To catalogue some of the many instruments
      that may be regarded by clinicians as worthwhile for use in measuring cognition
      and affect in clinical practice. MAIN CONTRIBUTION: The presentation of measures
      of cognition and affect is organized according to those that have appeared in
      recent clinical trials of stuttering during roughly the last decade, and those
      that have not featured in clinical trials. CONCLUSIONS: Measures that have
      featured in the clinical trials literature might be looked on favourably, along
      with those for whom there are more than one data source in support. The various
      measures from the discipline of clinical psychology generally fall into the
      latter category. The notions of cognition and affect emerge from the discipline
      of clinical psychology, and therefore it makes sense to look to that discipline
      for measures of those constructs. Seeking such tools outside the discipline of
      speech pathology, especially those with established reliability and validity,
      seems to hold potential in contributing to one's understanding of affective and
      cognitive functioning in people who stutter.

PMID- 16815804
TI  - Anorexia in cancer: role of feeding-regulatory peptides.
AB  - Anorexia is one of the most common symptoms in advanced cancer and is a frequent
      cause of discomfort for cancer patients and their families. The pathogenesis of
      cancer anorexia is multi-factorial and involves most of the hypothalamic neuronal
      signalling pathways modulating energy homeostasis. It is considered to be the
      result of a failure of usual appetite and satiety signals. Loss of appetite can
      arise from decreased taste and smell of food, as well as from dysfunctional
      hypothalamic signalling pathways and cytokine production. Cytokines in
      particular, appear to play a key role in energy balance through persistent
      activation of the melanocortin system and inhibition of the neuropeptide Y
      pathway. The imbalance between anorexigenic and orexigenic peptides leads to
      suppression of appetite, and increased satiety and satiation associated with
      marked weight loss and decline in physical performance. High levels of serotonin
      also appear to contribute to these effects and recent findings implicate
      corticotropin-releasing factor in the pathogenesis of cancer anorexia as well.
      Despite significant advances in our understanding of the regulation of food
      intake and energy expenditure, few effective therapies are available. A better
      appreciation of the molecular and neuronal mechanisms that control body weight
      homeostasis may lead to the development of new therapies for improving the
      survival and quality of life of these patients.

PMID- 16815807
TI  - Connecting stuttering measurement and management: III. Accountable therapy.
AB  - BACKGROUND: This paper is intended to contribute to the current debate in
      relation to persistent stuttering and evidence-based clinical practice. AIMS: The
      paper will describe the authors' intervention framework for persistent
      stuttering, which is guided by evidence from the fields of stuttering and
      clinical psychology. It supports the opinion that the components of therapy
      should be grounded in empirically based theories that offer an explanation for
      the nature of stuttering, its persistence and its individual complexity. It will
      argue that the goals of therapy should reflect the client's personal values and
      experience of stuttering, as well as the knowledge and skills of the therapist.
      MAIN CONTRIBUTION: The paper maintains that therapy for this disorder needs to
      account for the highly individual nature of the overt and covert dimensions of
      persistent stuttering and identify the formal and informal methods that measure
      progress and outcome. Current research and future directions will be touched on
      briefly.

PMID- 16815808
TI  - Connecting stuttering management and measurement: IV. Predictors of outcome for a
      behavioural treatment for stuttering.
AB  - BACKGROUND: Clinical trials have shown that behavioural treatments based on
      variants of prolonged-speech (PS) are best practice for reducing the stuttering
      rate in adults. However, while stuttering is significantly reduced or eliminated
      for most adults in the short-term with such treatment, relapse in the longer-term
      is common. Consequently, there has been interest in attempting to establish
      variables that predict responsiveness to PS-based treatments. Identifying such
      variables would enable risk prediction and also contribute to the tailoring of
      treatments to suit individuals who are less likely to benefit in the long-term
      from the conventional PS-based treatments. Variables that have been investigated
      to date are the stuttering severity, the attitude to communication and the locus
      of control. AIMS: The present study revisited this issue with methodological
      improvements. METHODS AND PROCEDURES: Prospective, continuous measures of outcome
      several years after treatment, and well-powered, least-squares multivariate
      regression, with backwards elimination, were used to determine the best model to
      predict short- and long-term outcomes of a PS-based treatment. Other predictor
      variables were also included. The stuttering rates of 78 participants were
      measured immediately after the intensive stage of treatment, and during a
      surprise telephone call 3.5-5 years after treatment. OUTCOMES AND RESULTS:
      Attitude to communication and locus of control were separate constructs to
      stuttering rate. While the stuttering rate predicted outcome, neither of the two
      non-behavioural variables predicted outcome in either the short- or the long
      term. CONCLUSIONS: The most significant finding is that the non-behavioural
      variables of attitude to communication and locus of control did not predict
      treatment outcomes. This is contrary to the findings of most previous studies.

PMID- 16815809
TI  - Connecting stuttering management and measurement: V. Deduction and induction in
      the development of stuttering treatment outcome measures and stuttering
      treatments.
AB  - BACKGROUND: The development of evidence-based practice, which is increasingly
      popular in stuttering treatment, is closely linked to the development of outcome
      measures. AIMS: Two approaches to the development of stuttering treatment outcome
      measures are outlined. The first is the deductive, top-down approach, where the
      development of specific outcome measures is guided by a priori general
      conceptualizations of the nature of the disorder. A competing approach to the
      development of stuttering treatment outcome measures is outlined. This is the
      inductive, or bottom up approach. This approach uses Baer's (1988, 1990) notion
      of specific complaints of clients as the starting point to develop inductive
      statements for use as general guidance for developing treatment outcome measures.
      MAIN CONTRIBUTION: It is argued that the deductive approach to development of
      outcome measures has limitations. It is overly prescriptive, generating numerous
      and increasingly complex outcome measures that are potentially confusing for
      clinicians. Further, it is arbitrary and fragile, being linked to
      conceptualizations and theories about stuttering, which, by necessity, are
      limited themselves. Further, the development of numerous outcome measures is not
      compatible with the conduct of randomized controlled trials, which allow a
      maximum of two primary outcome measures. In contrast, the inductive approach to
      the development of outcome measures has in its favour that it is empirically
      driven rather than arbitrary, and that it facilitates a yoking of the development
      of clinical outcomes and the clinical methods to attain those outcomes. The
      approach is unlikely to lead to the development of fruitless treatment methods.
      Further, the approach is parsimonious to the extent that it is likely to produce
      few guiding generalities for treatment outcome assessment -- perhaps as few as
      two in the case of adults and one in the case of preschoolers. This is well
      suited to the use of the randomized controlled trial as a source of evidence for
      treatment efficacy. CONCLUSIONS: One inductive statement that can be used to
      guide the development of outcome measures is that the ill effects of stuttered
      speech could be troubling for those who seek clinical help. The other is that
      those who seek clinical help are likely to experience speech-related anxiety.
      Together, these sources of information provide sound guidance for the development
      of outcome measures relating to stuttered speech and speech-related anxiety, and
      guidance for the development of treatments to offset those ill effects of the
      condition. Until another outcome measure can be derived from inductive processes,
      those treatment developments should serve all the needs of those who stutter and
      the clinicians who provide those needs.

PMID- 16815810
TI  - Educational provision for children with specific speech and language
      difficulties: perspectives of speech and language therapy service managers.
AB  - BACKGROUND: Children with specific speech and language difficulties (SSLD) pose a
      challenge to the education system, and to speech and language therapists who
      support them, as a result of their language needs and associated educational and
      social-behavioural difficulties. The development of inclusion raises questions
      regarding appropriate provision, whether the tradition of language units or full
      inclusion into mainstream schools. AIMS: To gather the views of speech and
      language therapy service managers in England and Wales regarding approaches to
      service delivery, terminology and decision-making for educational provision, and
      the use of direct and indirect (consultancy) models of intervention. METHOD AND
      PROCEDURES: The study reports on a national survey of speech and language therapy
      (SLT) services in England and Wales (129 respondents, 72.1% response rate) and
      interviews with 39 SLT service managers. OUTCOMES AND RESULTS: Provision varied
      by age group with support to children in the mainstream common from pre-school to
      the end of Key Stage 2 (up to 11 years), and to those in designated specialist
      provision, common at Key Stages 1/2 (ages 5-11 years), but less prevalent at Key
      Stages 3/4 (11-16 years). Decision-making regarding provision was influenced by
      the lack of common terminology, with SSLD and specific language impairment (SLI)
      the most common, and criteria, including the use of the discrepancy model for
      defining SSLD. Practice was influenced by the difficulties in distinguishing
      children with SSLD from those with autistic spectrum disorder, and difficulties
      translating policies into practice. CONCLUSIONS: The implications of the study
      are discussed with reference to SLT practice, including consultancy models, and
      the increasingly prevalent policy in local education authorities of inclusion of
      children with special educational needs.

PMID- 16815811
TI  - Interaction before conflict and conflict resolution in pre-school boys with
      language impairment.
AB  - BACKGROUND: Children with language impairment (LI) experience social
      difficulties, including conflict management. The factors involved in peer
      conflict progression in pre-school children with LI, and which of these processes
      may differ from pre-school children with typical language development (TL), is
      therefore examined. AIMS: To describe the relationship between opponents
      interacting before conflict, aberrant conflict causes, the conflict-resolution
      strategy reconciliation (i.e. friendly contact between former opponents shortly
      following conflict termination), and conflict outcome in the form of social
      interaction after a conflict has run its course. It is hypothesized that without
      social interaction before conflict, children with LI will experience increased
      difficulties attaining reconciliation. METHODS AND PROCEDURES: Unstructured play
      of 11 boys with LI (4-7 years old), at a specialized language pre-school, and 20
      boys with TL (4-6 years old), at mainstream pre-schools, were video filmed.
      Conflicts were identified and recorded according to a validated coding system.
      Recorded conflict details include social interaction between conflict in the pre
      conflict period, behavioural sequences constituting conflict cause (conflict
      period), reconciliatory behaviours in the post-conflict period, and social
      interaction between former opponents in the succeeding non-conflict period. The
      group's mean proportion of individual children's conflicts in which specific
      behavioural sequences occurred were calculated and compared between and within
      the groups. OUTCOMES AND RESULTS: When conflicts with and without pre-conflict
      social interaction were analysed separately, aberrant caused conflicts occurred
      more often in LI group conflicts than in TL group conflicts. However, in
      conflicts without social interaction in the pre-conflict period, boys with LI
      exhibit reconciliatory behaviours in, and reconcile a comparatively smaller
      proportion of, conflicts. Social interaction in the succeeding non-conflict
      period was proportionately less for boys with LI. This appears to stem from lower
      reconciliation rates in LI conflicts that do not begin with social interaction in
      the pre-conflict period. It was also confounded by the larger number of aberrant
      caused LI conflicts that were rarely reconciled. In turn, non-reconciliation and
      aberrant caused conflicts were independently associated with comparatively less
      social interaction in the succeeding non-conflict period. CONCLUSIONS: The
      results suggest that in addition to traditional psycholinguistic training,
      children with LI may gain from interventions that support concluding behavioural
      turns, as in aberrant caused conflicts; and in initiating contact in conflict
      situations, even when a frame of reference is not immediately available, as was
      the case when opponents have not established social interaction in the pre
      conflict period.

PMID- 16815813
TI  - Structure, function, expression, genomic organization, and single nucleotide
      polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux
      transporters.
AB  - The ATP-binding cassette (ABC) transporters constitute a large family of membrane
      proteins, which transport a variety of compounds through the membrane against a
      concentration gradient at the cost of ATP hydrolysis. Substrates of the ABC
      transporters include lipids, bile acids, xenobiotics, and peptides for antigen
      presentation. As they transport exogenous and endogenous compounds, they reduce
      the body load of potentially harmful substances. One by-product of such
      protective function is that they also eliminate various useful drugs from the
      body, causing drug resistance. This review is a brief summary of the structure,
      function, and expression of the important drug resistance-conferring members
      belonging to three subfamilies of the human ABC family; these are ABCB1 (MDR1/P
      glycoprotein of subfamily ABCB), subfamily ABCC (MRPs), and ABCG2 (BCRP of
      subfamily ABCG), which are expressed in various organs. In the text, the
      transporter symbol that carries the subfamily name (such as ABCB1, ABCC1, etc.)
      is used interchangeably with the corresponding original names, such as MDR1P
      glycoprotein, MRP1, etc., respectively. Both nomenclatures are maintained in the
      text because both are still used in the transporter literature. This helps
      readers relate various names that they encounter in the literature. It now
      appears that P-glycoprotein, MRP1, MRP2, and BCRP can explain the phenomenon of
      multidrug resistance in all cell lines analyzed thus far. Also discussed are the
      gene structure, regulation of expression, and various polymorphisms in these
      genes. Because genetic polymorphism is thought to underlie interindividual
      differences, including their response to drugs and other xenobiotics, the
      importance of polymorphism in these genes is also discussed.

PMID- 16815814
TI  - History of toxicology and allied sciences: a bibliographic review and guide to
      suggested readings.
AB  - With roots extending to antiquity, toxicology is a profession that recognizes
      that the past is often prologue to the present. In that spirit, this article
      provides a comprehensive bibliographic overview of writings on the history of
      toxicology and allied sciences. These writings pertain to the evolution of
      toxicology, its various methods, concepts, and theories; as well as pioneers of
      the profession and the growth of professional toxicological organizations. It is
      not an exhaustive survey, but provides a thorough accounting of literature
      pertaining to the history of toxicology.

PMID- 16815815
TI  - A perspective on the safety of cosmetic products: a position paper of the
      American Council on Science and Health.
AB  - Over the years, some activist groups have targeted cosmetics as possible human
      health threats, claiming that cosmetic ingredients are not adequately tested for
      safety and may pose risks to consumers. The groups allege that industry practices
      related to safety testing are flawed, that there is little government oversight,
      and that cosmetics contain cancer-causing chemicals and other toxicants. A
      critical review of the scientific data related to these claims indicates the
      following: (1) Industry has the primary responsibility to ensure that all
      ingredients, preservatives, and coformulants used in products are safe for their
      intended uses. (2) The U.S. Food and Drug Administration (FDA) has regulatory
      oversight of the cosmetic industry. Its authority includes the banning or
      restriction of ingredients for safety reasons. (3) The Cosmetic Ingredient Review
      (CIR), an independent, scientific review board, critically evaluates chemical
      ingredients used in cosmetics and publishes the results of its findings in the
      peer-reviewed literature. (4) Health-related allegations about cosmetic
      ingredients are generally based on the results of high-dose laboratory testing in
      animals and have little relevance for humans. As true now as when Paracelsus said
      it in the 16th century, "It is the dose that makes the poison." (5) The health
      related allegations involving specific chemicals (e.g., phthalates, parabens, and
      1,3-butadiene) fail to consider important scientific studies and recent
      regulatory conclusions about these chemicals, which have found that they are not
      hazardous. (6) Animal and human physiology differ in crucial ways, further
      invalidating simplistic attempts to extrapolate rodent testing to human health
      risks. The cosmetic industry should be encouraged to publish more of its toxicity
      studies and safety evaluations, which would aid in dispelling the uncertainty
      that some consumers have about cosmetic safety.

PMID- 16815816
TI  - Trichloroethylene, trichloroacetic acid, and dichloroacetic acid: do they affect
      eye development in the Sprague-Dawley rat?
AB  - Maternal exposure to high doses of trichloroethylene (TCE) and its oxidative
      metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), has been
      implicated in eye malformations in fetal rats, primarily micro-/anophthalmia.
      Subsequent to a cardiac teratology study of these compounds (Fisher et al. 2001,
      Int. J. Toxicol. 20:257-267), their potential to induce ocular malformations was
      examined in a subset of the same experimental animals. Pregnant, Sprague-Dawley
      Crl:CDR BR rats were orally treated on gestation days (GDs) 6 to 15 with bolus
      doses of either TCE (500 mg/kg/day), TCA (300 mg/kg/day), DCA (300 mg/kg/day), or
      all-trans retinoic acid (RA; 15 mg/kg/day). The heads of GD 21 fetuses were not
      only examined grossly for external malformations, but were sectioned using a
      modified Wilson's technique and subjected to computerized morphometry that
      allowed for the quantification of lens area, globe area, medial canthus distance,
      and interocular distance. Gross ocular malformations were essentially absent in
      all treatment groups except for the RA group in which 26% of fetuses exhibited
      micro-/anophthalmia. Using the litter as the experimental unit of analysis, lens
      area, globe area, and interocular distance were statistically significantly
      reduced in the DCA treatment group. Statistically significant reductions in lens
      and globe areas also occurred in the RA treatment group, all four ocular measures
      were reduced in the TCA treatment group but none significantly so, and TCE was
      without effect. Because DCA, TCA, and RA treatments were associated with
      significant reductions in fetal body weight (bw), data were also statistically
      analyzed after bw adjustment. Doing so dramatically altered the results of
      treatment group comparisons, but the severity of bw reduction and the degree of
      change in ocular measures did not always correlate. This suggests that bw
      reduction may not be an adequate explanation for all the changes observed in
      ocular measures. Thus, it is unclear whether DCA specifically disrupted ocular
      development even under these provocative exposure conditions. Clearly, however,
      if TCE is capable of disrupting ocular development in the Sprague-Dawley rat, a
      higher dose than that employed in the present study is required.

PMID- 16815818
TI  - The effects of natural flavonoids on lipoxygenase-mediated oxidation of compounds
      with a benzene ring structure--a new possible mechanism of flavonoid anti
      chemical carcinogenesis and other toxicities.
AB  - Numerous studies have strongly suggested that flavonoids exhibit antimutagenic,
      anticarcinogenic, antiallergic, and anti-inflammatory properties, but the
      mechanism is still far from clear. In this study, the effect of natural flavonoid
      compounds, such as green tea polyphenol, epigallocatechin gallate, quercetin, and
      rutin on lipoxygenase-mediated co-oxidation of guaiacol, benzidine,
      paraphenylenediamine, and dimethoxybenzidine was investigated. Green tea
      polyphenol, epigallocatechin gallate, quercetin, and rutin can reduce the co
      oxidation reaction speed of tested compounds mediated by soybean lipoxygenase and
      the production of oxidative products and free radical intermediates. Their median
      inhibition concentrations on guaiacol oxidation mediated by soybean lipoxygenase
      were 8.22 mg.L-1, 17.8 micromol.L-1, 41.5 micromol.L-1, and 46.3 micromol.L-1,
      respectively. These were all significantly lower than glutathione,
      dithiothreitol, butylated hydroxyanisole and gossypol. The data collected in this
      study suggest that flavonoids may have an anticarcinogenicity and antitoxicity
      effect through inhibition of oxidative activation.

PMID- 16815817
TI  - Safety evaluation of ABELCET, an amphotericin B lipid complex (ABLC): toxicity
      studies in rats.
AB  - ABELCET (ABLC) is a widely used amphotericin B lipid complex formulation that is
      approved for use in the treatment of invasive fungal infections in patients who
      are refractory or intolerant of conventional amphotericin B (AmB). The safety
      profile of ABLC has been characterized in two acute and two repeat-dose toxicity
      studies in rats. The acute toxicity studies indicated that single intravenous
      doses of ABLC are at least 20 times less toxic than conventional amphotericin B
      doses without the lipid formulation, Fungizone. Intravenous doses of 0, 1, 3, or
      10 mg/kg/day to groups of rats (10 to 15 rats/sex/group) for 31 days elicited no
      mortality or overt clinical signs of toxicity, whereas alternate
      intravenous/intraperitoneal doses (three each per week) for 6 months, produced
      one death in the control group, one in the intermediate-dose group, and two in
      the high-dose group. Clinical signs (predominantly piloerection and hunched
      posture at 10 mg/kg/day) were attributed to granulomatous inflammatory lesions in
      the abdominal wall, mesentery, and omentum, which were produced by the
      intraperitoneal injections of ABLC. Feed consumption and body weight gains
      decreased in high-dose male rats in the one-month study and were significantly
      lower in male rats at 3 and 10 mg/kg/day in the 6-month study. In contrast, water
      consumption increased in male and female rats in both studies. Trends of minimal
      to moderate, dose-related increases in relative kidney, liver and spleen weights,
      and histological evidence of hypertrophy and hyperplasia of reticuloendothelial
      cells in the liver and spleen and mild, dose-related impairment of renal function
      occurred in both the 1- and 6-month studies. Examination of high-dose rats
      following a recovery period of 28 days after completion of 31 days of dosing
      suggested that treatment-related changes were reversible. The observed changes
      for ABLC are similar to those for other amphotericin B lipid formulations, such
      as AmBisome (LAmB), except for the hepatoxicity, which was observed for LAmB, but
      not for ABLC.

PMID- 16815819
TI  - Arsenite increases vasoconstrictor reactivity in rat blood vessels: role of
      endothelial nitric oxide function.
AB  - Arsenite has been shown to inhibit endothelium-dependent, nitric oxide-mediated
      vasodilation in vitro. This study investigated the effects of arsenite on
      vascular reactivity in vivo. Saline or sodium arsenite (6 mg kg-1) was
      administered intravenously in Wistar-Kyoto rats for 4 h. As compared to saline,
      arsenite significantly increased vasoconstrictor responses to phenylephrine in
      both rat isolated aorta and renal arteries examined in tissue bath. This change
      was diminished after preincubation of the tissues with the nitric oxide synthase
      inhibitor NG-nitro-L-arginine methyl ester, which increased phenylephrine-induced
      vasoconstriction to a similar extent as arsenite. In contrast, acetylcholine
      induced vasodilation, mediated by nitric oxide in the aorta and by an endothelium
      derived hyperpolarizing factor in renal arteries, was not affected by arsenite.
      Arsenite induced expression of heat shock proteins Hsp72, Hsp32, and Hsp90, but
      endothelial nitric oxide synthase expression was not changed. The effects of
      arsenite on vasoreactivity were unlikely to be mediated by heat shock protein
      induction, because blockade of heat shock protein induction had little effect on
      the increased vasoconstriction in vessels from arsenite-treated animals. Our
      study suggests that in vivo arsenic treatment increases vasoconstrictor
      reactivity by compromising basal endothelial nitric oxide function, which is not
      caused by altered endothelial nitric oxide synthase expression.

PMID- 16815821
TI  - Electrotonic transmission within pericyte-containing retinal microvessels.
AB  - OBJECTIVE: Little is known about the electrotonic architecture of the pericyte
      containing retinal microvasculature. Here, the authors focus on the cell-to-cell
      transmission of hyperpolarization, which can induce abluminal pericytes to relax
      and lumens to dilate. METHODS: With perforated-patch pipettes, the authors
      monitored the membrane potentials and ionic currents of pairs of pericytes
      located on freshly isolated rat retinal microvessels. Voltage changes were
      induced by administering electrical stimuli into pericytes, miniperfusing the
      KATP channel opener pinacidil, or using oxotremorine to activate chloride
      channels. RESULTS: Suggestive of extensive cell-to-cell communication,
      spontaneous voltage changes were strikingly similar in widely separated
      pericytes. In addition, injection of current into one of a pair of sampled
      pericytes always elicited a voltage response in the other sampled pericyte; the
      gap junction uncoupler, heptanol, blocked this transmission. In the dual
      recordings, hyperpolarization spreading from a current-injected pericyte decayed
      approximately 40% within 100 microm. In contrast, pinacidil-induced
      hyperpolarizations diminished by only approximately 2% in 100 microm.
      Depolarizations also appeared to spread with similar transmission efficacies.
      CONCLUSIONS: Based on the experiments, the authors propose that key features of
      the electrotonic architecture of retinal microvessels include highly efficient
      cell-to-cell communication within the endothelium and relatively inefficient
      transmission at pericyte/endothelial junctions. Thus, the endothelium is likely
      to provide an efficient pathway that functionally links contractile pericytes and
      thereby, serves to coordinate the vasomotor response of a retinal capillary.

PMID- 16815822
TI  - Recanalization of the collecting lymphatics in rabbit hind leg.
AB  - OBJECTIVE: This study was designed to examine whether mature collecting
      lymphatics can regenerate in the adult tissue or not. MATERIALS AND METHODS: The
      X-ray lymphograms were used to detect network of the collecting lymphatics in
      rabbit hind leg. Regeneration of the lymphatics was observed after surgical
      removal of the popliteal lymph node or a part of the popliteal afferent
      lymphatic. Structure and mechanical properties of the lymphatics were also
      examined by light and electron microscopes and in vitro functional experiments.
      RESULTS: One week after removal of the lymph node, only an afferent lymphatic and
      a deposit of the contrast medium at the popliteal region were observed. Four
      weeks after the removal, the connection of the afferent and efferent lymphatics
      at the popliteal region, and collateral lymphatics were present in the leg.
      Further, 4 weeks after 1-mm excisions of a part of the lymphatic, recanalization
      was observed between the central and peripheral cut ends of the lymphatic but not
      after 3- and 10-mm excisions. Endothelial cells and smooth muscle cells could be
      observed by electron microscope, and contractile proteins, and alpha-smooth
      muscle actin SM1 and SM2 were immunofluorescently detected in both intact and the
      regenerated lymphatic walls. In both lymphatics, norepinephrine and acetylcholine
      induced dose-dependent constriction and dilation of the vessels, respectively.
      CONCLUSION: The present study demonstrated that mature collecting lymphatics are
      able to regenerate in the adult tissues.

PMID- 16815823
TI  - Role of platelets in hypercholesterolemia-induced leukocyte recruitment and
      arteriolar dysfunction.
AB  - OBJECTIVE: To define the contribution of platelets, specifically platelet
      associated P-selectin, to the altered venular and arteriolar responses induced by
      hypercholesterolemia. METHODS: Leukocyte and platelet recruitment in cremasteric
      venules, and endothelium-dependent relaxation (EDR) in arterioles were determined
      using intravital videomicroscopy. Wild-type (WT) mice were placed on a normal or
      high cholesterol diet. Hypercholesterolemic mice were treated with blocking
      antibodies against either P-selectin or PSGL-1, or were depleted of neutrophils
      (ANS) or platelets (APS). Bone marrow chimeras (P-selectin deficiency in
      platelets, but not in endothelial cells) were produced by transplanting bone
      marrow from P-selectin-/- into WT mice (P-sel-/---> WT). RESULTS:
      Hypercholesterolemia (HC) elicited the recruitment of adherent platelets and
      leukocytes in venules and an impaired EDR in arterioles. The exaggerated cell
      adhesion responses were absent in hypercholesterolemic mice treated with ANS,
      anti-P-selectin or anti-PSGL-1 antibodies and in P-sel-/---> WT chimeras. The
      hypercholesterolemia-induced impairment of arteriolar EDR was significantly
      blunted in mice rendered either neutropenic or thrombocytopenic, and in P-sel-/--
      > WT chimeras. CONCLUSIONS: The findings indicate that platelet-associated P
      selectin contributes to the recruitment of leukocytes and platelets in venules of
      hypercholesterolemic mice and that the P-selectin-mediated adhesive interactions
      also contribute to the impaired arteriolar function induced by
      hypercholesterolemia.

PMID- 16815824
TI  - Impact of obesity on coronary microvascular function in the Zucker rat.
AB  - OBJECTIVE: To test the hypothesis that vasomotor control is impaired in the
      coronary circulation of prediabetic obese (OZR) relative to lean Zucker rats
      (LZR). METHODS: Cardiac function was assessed with in vivo measures of cardiac
      output and microvascular structure and function was assessed in vitro using
      videomicroscopic techniques. RESULTS: OZR showed a marked hyperdynamic
      circulation with an increased cardiac output and elevated stroke volume. Contrary
      to the stated hypothesis, the authors found no diminution of vasodilator function
      and no augmentation of vasoconstriction. Indeed, dilation to acetylcholine was
      potentiated and vasoconstriction to endothelin was reduced in OZR compared to
      LZR. Structural characteristics of small coronary arteries were similar between
      LZR and OZR. CONCLUSIONS: Taken together, these results indicate that obesity, as
      manifested in the prediabetic OZR, does not impair coronary vasomotor control.
      This lack of dysfunction in the presence of the same risk factors that affect
      other beds may reflect a reversal of vascular injury by the increased metabolism
      and coronary blood flow caused by hyperdynamic cardiac function early in obesity.

PMID- 16815825
TI  - Acute isovolemic hemodilution triggers proinflammatory and procoagulatory
      endothelial activation in vital organs: role of erythrocyte aggregation.
AB  - OBJECTIVES: The essential role of erythrocytes as oxygen carriers is historically
      well established, but their function to aggregate and the consequences on the
      microcirculation is under debate. The pathogenic potential of low erythrocyte
      aggregation could be important for patients undergoing on-pump cardipopulmonary
      bypass. These patients are severely hemodiluted due to preoperative isovolemic
      hemodilution (IHD), circuit priming, and large fluid infusions perioperatively.
      Considering the vascular endothelium sensitivity to variations in blood rheology,
      the authors hypothesize that low erythrocyte aggregation will be responsible for
      activation of vascular endothelium during acute IHD. METHODS: Acute IHD (30 mL/kg
      exchange transfusion with colloid solutions) was induced in an "aggregating
      species"(pigs, n = 15). The hypoxic oxidative stress (plasma malondialdehyde, ex
      vivo oxygen radicals production in heart, lung, kidney, liver, and ileum tissue
      biopsies), erythrocyte aggregation (LORCA), and endothelial activation (real-time
      quantitative RT-PCR on von Willebrand factor (vWF), E- and P-selectins,
      endothelial nitric oxide synthase gene-expression in tissue biopsies) were
      investigated. RESULTS: The production of superoxide and hydroxyl radicals,
      measured as H2O2 generation, was similar at all times in sham-operated and
      hemodiluted animals, proving a maintained oxygen delivery to tissues. Acute IHD
      was followed by a dramatic drop in erythrocyte aggregation and immediate
      prothrombotic (significant vWF mRNA upregulation in heart, lungs, kidney, liver,
      ileum) and proinflammatory (significant E- and P-selectins mRNA upregulation in
      lungs and ileum) endothelial activation. Low erythrocyte aggregation was
      significantly correlated with increased mRNA-expression of vWF (heart, liver,
      ileum) and P-selectin (lungs, ileum, and heart). CONCLUSIONS: These results
      suggest that low erythrocyte aggregation might trigger endothelium-dependent
      thrombogenic and proinflammatory response during acute isovolemic hemodilution.

PMID- 16815826
TI  - Shunting of the microcirculation after mesenteric ischemia and reperfusion is a
      function of ischemia time and increases mortality.
AB  - OBJECTIVE: Shunting of the microcirculation contributes to the pathology of
      sepsis and septic shock. The authors address the hypothesis that shunting of the
      microcirculation occurs after superior mesenteric artery occlusion (SMAO) and
      reperfusion, and explore functional consequences. METHODS: Spontaneously
      breathing animals (rats) (n = 30) underwent SMAO for 0 (controls), 30 (SMAO_30)
      or 60 min (SMAO_60) followed by reperfusion (4 h) with normal saline. Leukocyte
      endothelial interactions in mesenteric venules were quantified in an exteriorized
      ileal loop using intravital microscopy. Abdominal blood flow was recorded
      continuously, and arterial blood gases were analyzed at intervals. The above
      groups were matched by comparable groups with continuous superior mesenteric
      artery blood flow measurements and without exteriorizing an ileal loop
      (controls*, SMAO_30*, SMAO_60*). RESULTS: Adherent leukocytes increased shortly
      after reperfusion in ischemia groups, and plateaued in these groups. Centerline
      velocity in the recorded venules was significantly reduced after reperfusion down
      to low-flow/no-flow in SMAO_60 as compared to SMAO_30 and controls, whereas
      perfusion of the SMA and ileal vessels persisted. The microcirculatory changes in
      SMAO_60 were accompanied by progressive metabolic acidosis, substantially larger
      volumes of intravenous fluids needed to support arterial blood pressure and
      significantly reduced survival (30%). SMA blood flow increased in relation to
      abdominal blood flow after reperfusion in SMAO_60*, and remained constant in
      SMAO_30* and controls*. Survival was 80% in SMAO_60*. CONCLUSION: Shunting of the
      microcirculation can be observed after SMAO for 60 min and reperfusion, and
      contributes significantly to the pathology of mesenteric ischemia and poor
      outcome.

PMID- 16815827
TI  - Twilight far-red treatment advances leaf bud burst of silver birch (Betula
      pendula).
AB  - Bud development of boreal trees in spring, once initiated, is driven by ambient
      air temperature, but the mechanism triggering bud development remains unclear. We
      determined if some aspect of the diurnal or seasonal light regime influences
      initiation of bud burst once the chilling requirement is met. We grew 3-year-old
      birch plantlets cloned from a mature tree of boreal origin in light conditions
      realistically simulating the lengthening days of spring at 60 degrees N. To
      emulate the reduction in red to far-red light (R:FR) ratio between daylight and
      twilight, one group of plantlets was subjected to reduced R:FR ratio in the
      morning and evening in addition to progressively lengthening days, whereas the
      other group was subjected to the same R:FR ratio throughout the day. The reduced
      R:FR ratio of twilight advanced bud burst by 4 days compared with the reference
      group (P = 0.04). To assess the interplay between the fulfillment of the chilling
      requirement and the subsequent response to warming, we fitted a thermal time
      model to the data with separate parameterizations for the starting dates of heat
      sum accumulation in each treatment. Least-squares fitting suggested that bud
      development started in light regimes corresponding to late March, almost two
      months after the chilling requirement for dormancy release was satisfied.
      Therefore, shortening night length or increasing day length, or both, appears to
      be the cue enabling bud development in spring, with twilight quality having an
      effect on the photoperiodic response. If twilight alone were the cue, the
      difference in bud burst dates between the experimental groups would have been
      greater than 4 days. The result gives experimental support for the use of thermal
      time models in phenological modeling.

PMID- 16815829
TI  - Foliar application of GA3 during terminal long-shoot bud development stimulates
      shoot apical meristem activity in Pinus sylvestris seedlings.
AB  - The effect of exogenous gibberellin (GA3) on shoot apical meristem activity in
      conifer vegetative buds was investigated by spraying 0 or 0.1% GA3 on the foliage
      of first-year Scots pine (Pinus sylvestris L.) seedlings twice weekly for 9 weeks
      during development of the terminal long-shoot bud. Exogenous GA3 promoted mitotic
      activity in the apical zone, thereby increasing both the rate and duration of
      cataphyll formation and giving rise to a higher and wider apical meristem. The
      increase in number of cataphylls increased the number of axillary meristems,
      which developed as short-shoot buds.

PMID- 16815828
TI  - Molecular characterization of PgAGO, a novel conifer gene of the Argonaute family
      expressed in apical cells and required for somatic embryo development in spruce.
AB  - A new member of the Argonaute (AGO) family of proteins was isolated from conifers
      and designated as PgAGO (Gene Bank Accession No. DQ068741; protein ID AAY67884).
      The complete coding sequence of PgAGO was obtained through screening cDNA
      libraries generated from white spruce (Picea glauca (Moench) Voss) somatic
      embryos. The PgAGO gene has an open reading frame of 2880 bp and encodes a
      protein of 960 amino acids. The predicted protein has an isolectric point of
      9.17, a molecular mass of 107 kD and lacks prominent hydrophobic domains, which
      makes its cellular location inconclusive. The PgAGO protein contains the two
      conserved regions (the PAZ and PIWI domains) typically found in all members of
      the AGO family. The PAZ domain of PgAGO comprises 117 amino acid residues and
      shares a low degree of homology with similar domains in other species. The C
      terminal PIWI domain contains 86 amino acids and is more conserved. Localization
      and transformation studies suggest that PgAGO is required for embryo development,
      specifically for proper shoot and root apical meristem differentiation. Based on
      RNA-in situ hybridization, the PgAGO transcripts are preferentially localized in
      cells of the shoot and root apical meristems from the early phases of embryo
      development. The RNA-mediated suppression of PgAGO results in severe
      abnormalities during embryo development, including the formation of poorly
      organized apical meristems. The root meristems lack the group of large central
      cells that separate the procambial region from the root cap, whereas the shoot
      meristem fails to differentiate apical initials. These abnormalities result in
      poor post-embryonic performance, leading to meristem abortion and growth
      cessation.

PMID- 16815830
TI  - Vertical and horizontal water redistribution in Norway spruce (Picea abies) roots
      in the Moravian Upland.
AB  - Hydraulic redistribution (HR) by roots of large Norway spruce (Picea abies (L.)
      Karst.) trees was investigated by means of sap flow measurements made with the
      heat field deformation method. Irrigation was applied to a limited portion of the
      root system to steepen gradients of water potential in the soil and thus enhance
      rates of HR. On completion of the sap flow measurements, and to aid in their
      interpretation, the structure of the root system of seven of the investigated
      trees was exposed to a depth of 30 cm with a supersonic air-stream (air-spade).
      Before irrigation, vertical redistribution of water was observed in large coarse
      roots and some adjacent small lateral roots. Immediately after localized
      irrigation, horizontal redistribution of water from watered roots to dry roots
      via the stem base was demonstrated. The amount of horizontal distribution
      depended on the position of the receiving roots relative to the watered roots and
      the absorbing area of the watered root. No redistribution from watered roots via
      dry soil to roots of neighboring trees was detected. Responses of sap flow to
      localized irrigation were more pronounced in small lateral roots than in large
      branching roots where release and uptake of water are integrated. Sap flow
      measurements with multi-point sensors along radii in large lateral roots
      demonstrated water extraction from different soil horizons. We conclude that
      synchronous measurements of sap flow in both small and large lateral roots are
      needed to study water absorption and transport in tree root systems.

PMID- 16815831
TI  - Selecting earlywood vessels to maximize their environmental signal.
AB  - The anatomical features of earlywood vessels often reflect information about past
      climatic conditions. We examined the relationships between mean monthly
      temperature and mean vessel lumen area (MVA) in various categories of earlywood
      vessels. Subsets of earlywood vessels of chestnut (Castanea sativa Mill.) were
      selected from a previously reported dataset based on several progressive size
      related procedures. To include all earlywood vessels, the minimum size considered
      was 10,000 microm2. Changes in the correlations between MVA and the mean air
      temperature in March are described and discussed. The results show that not all
      vessels embody the same information. The MVA of a proportion of the largest
      earlywood vessels in each annual ring was most closely related to March
      temperature, whereas MVA of the smallest earlywood vessels was better correlated
      with June temperature. This difference is probably a result of the vessels being
      formed at different times: early spring for the largest earlywood vessels and
      later in spring for the smallest earlywood vessels. Analyses combining large and
      small vessels yielded lower correlations between MVA and monthly temperature. The
      number, size and distribution of vessels can vary greatly from ring to ring. In
      making year-to-year comparisons, the best information is provided by observations
      on vessels of contemporaneous ontogenesis. Criteria for the selection and
      analysis of vessels in the assessment of temperature during the season of wood
      formation are proposed and discussed.

PMID- 16815833
TI  - Seasonal changes in photosynthesis, nitrogen content and nitrogen partitioning in
      Lindera umbellata leaves grown in high or low irradiance.
AB  - Seasonal changes in photosynthetic capacity, leaf nitrogen (N) content and N
      partitioning were studied from before leaf maturation (spring) until death
      (autumn) in high- and low-light-exposed leaves of a deciduous shrub, Lindera
      umbellata var. membranacea (Maxim.) Momiyama growing in a natural forest in
      northeast Japan. In spring, light-saturated photosynthetic rate (Pmax) was low
      despite high leaf N and Rubisco contents, indicating that the photosynthetic
      apparatus was not yet functionally developed. Rubisco seemed to be only partially
      active. In summer and autumn, Pmax per unit leaf N increased and changes in Pmax
      were correlated with changes in leaf N and two photosynthetic components, Rubisco
      and chlorophyll. Changes in these components paralleled the changes in leaf N.
      During leaf senescence, about 70% of leaf N was resorbed. Metabolic proteins that
      accounted for the majority of leaf N in summer were highly degradable and more
      than sufficient to explain the high N-resorption efficiency. Structural proteins
      represented only a small part of leaf N and were relatively resistant to
      degradation and thus contributed little to N resorption. Leaf N partitioning
      between metabolic and structural proteins determined the amount of
      retranslocatable N, but did not strictly determine the N content of a dead leaf
      or N-resorption efficiency.

PMID- 16815832
TI  - Correlating gene expression to physiological parameters and environmental
      conditions during cold acclimation of Pinus sylvestris, identification of
      molecular markers using cDNA microarrays.
AB  - Scots pine (Pinus sylvestris L.) seedlings were grown under different conditions
      (three field locations, two seasons and two climate room regimes), and then
      analyzed for freezing tolerance of shoots and roots and for transcript abundance
      in apical buds based on a cDNA microarray containing about 1500 expressed
      sequence tags (ESTs) from buds of cold-treated Scots pine seedlings. In a climate
      room providing long daily photoperiods and high temperatures, seedlings did not
      develop freezing tolerance, whereas seedlings in a climate room set to provide
      declining temperatures and day lengths developed moderate freezing tolerance.
      Control seedlings grown outside under field conditions developed full freezing
      tolerance. Differences in physiological behavior of the different seedling
      groups, combined with molecular analysis, allowed identification of a large group
      of genes, expression of which changed during the development of freezing
      tolerance. Transcript abundance of several of these genes was highly correlated
      with freezing tolerance in seedlings differing in provenance, field location or
      age, making them excellent candidate marker genes for molecular tests for
      freezing tolerance.

PMID- 16815834
TI  - Impact of eastern dwarf mistletoe (Arceuthobium pusillum) infection on the
      needles of red spruce (Picea rubens) and white spruce (Picea glauca): oxygen
      exchange, morphology and composition.
AB  - Eastern dwarf mistletoe (Arceuthobium pusillum Peck) is a hemiparasitic
      angiosperm that infects white spruce (Picea glauca (Moench) Voss) and red spruce
      (P. rubens Sarg.) in northeastern North America. The effects of mistletoe
      infection differ substantially between white and red spruce, with white spruce
      suffering greater infection-induced mortality. In the present study, we sought to
      determine the role that species-specific differences in needle-scale responses to
      parasitism may play in the observed differences in the effect of infection on
      host tree health. Based on the measurements made, the most apparent effect of
      parasitism was a reduction in needle size distal to infections. The magnitude of
      this reduction was greater in white spruce than in red spruce. Eastern dwarf
      mistletoe was a sink for host photosynthate in red spruce and white spruce;
      however, there were no adjustments in needle photosynthetic capacities in either
      host to accommodate the added sink demands of the parasite. Needle total
      nonstructural carbohydrate concentrations (TNC) were also unaltered by infection.
      Red spruce needles had higher TNC concentrations despite having lower overall
      photosynthetic capacities, suggesting that red spruce may be more sink limited
      and therefore better able to satisfy the added sink demands of parasitic
      infection. However, if carbon availability limits the growth of the mistletoe,
      one may expect that the extent of the parasitic infection would be greater in red
      spruce. Yet in the field, the extent of infection is generally greater in white
      spruce. Taken together, these results suggest that dwarf mistletoe may not
      substantially perturb the carbon balance of either host spruce species and that
      species-specific differences in needle-scale responses to the parasite cannot
      explain the contrasting effects of infection on white spruce and red spruce.

PMID- 16815835
TI  - Relationship of water status to vegetative growth and leaf gas exchange of peach
      (Prunus persica) trees on different rootstocks.
AB  - We investigated relationships between tree water status, vegetative growth and
      leaf gas exchange of peach trees growing on different rootstocks under field
      conditions. Tree water status was manipulated by partially covering (0,
      approximately 30 and approximately 60%) the tree canopies on individual days and
      then evaluating the effects of tree water status on vegetative growth and leaf
      gas exchange. Early morning stem water potentials were approximately -0.4 MPa for
      trees in all treatments, but mean midday values ranged from -1.1 to -1.7 MPa
      depending on rootstock and canopy coverage treatment. Relative shoot extension
      growth rate, leaf conductance, transpiration rate and net CO2 exchange rate
      differed significantly among trees in the different rootstocks and canopy
      coverage treatments. Shoot extension growth rate, leaf conductance, leaf
      transpiration rate and leaf net CO2 exchange rate were linearly correlated with
      midday stem water potential. These relationships were independent of the
      rootstock and canopy coverage treatments, indicating that tree water relations
      are probably directly involved in the mechanism that imparts vegetative growth
      control by selected peach rootstocks.

PMID- 16815836
TI  - Hydraulic conductance characteristics of peach (Prunus persica) trees on
      different rootstocks are related to biomass production and distribution.
AB  - We investigated hydraulic conductance characteristics and associated dry matter
      production and distribution of peach trees grafted on different rootstocks
      growing in the field. A single scion genotype was grown on a low ('K146-43'), an
      intermediate ('Hiawatha') and a high ('Nemaguard') vigor rootstock. 'K146-43' and
      'Hiawatha' rootstocks had 27 and 52% lower mean leaf-specific hydraulic
      conductances, respectively, than the more vigorous 'Nemaguard' rootstock. Tree
      growth rates and patterns of biomass distribution varied significantly among
      rootstocks. Mean dry mass relative growth rates of trees on 'K146-43' and
      'Nemaguard' were 66 and 75%, respectively, of the rates of trees on 'Nemaguard',
      and the scion to rootstock dry mass ratios of trees on 'K146-43' and 'Hiawatha'
      were 63 and 82%, respectively, of the ratio of trees on 'Nemaguard'. Thus,
      differences in dry matter distribution between the scion and rootstock, which may
      be a compensatory response to the differences in leaf specific hydraulic
      conductance among rootstocks, appeared to be related to differences in growth
      rates. Correspondingly, there was a positive linear relationship between the
      scion to rootstock dry mass ratio and the rootstock to scion hydraulic
      conductance ratio when conductance was normalized for dry mass. This study
      confirms that rootstock effects on tree water relations and vegetative growth
      potential result, at least in part, from differences in tree hydraulic
      conductance associated with specific peach rootstocks.

PMID- 16815837
TI  - Responses of secondary chemicals in sugar maple (Acer saccharum) seedlings to UV
      B, springtime warming and nitrogen additions.
AB  - Anticipated effects of climate change involve complex interactions in the field.
      To assess the effects of springtime warming, ambient ultraviolet-B radiation (UV
      B) and nitrogen fertilization on the foliar chemistry and herbivore activity of
      native sugar maple (Acer saccharum Marsh.) seedlings, we carried out a field
      experiment for 2 years at two sugar maple forests growing on soils of contrasting
      acidity. At the Oliver site, soils are derived from a strongly calcareous till,
      whereas the naturally acidic soils and base-poor soils of the Haliburton site are
      derived from the largely granitic Precambrian Shield. At both sites, removal of
      ambient UV-B led to increases in chlorogenic acid and some flavonoids and reduced
      herbivore activity. At Haliburton, ammonium nitrate fertilization led to further
      increases in foliar manganese (Mn), whereas at Oliver there were no such changes.
      Nitrogen additions led to decreases in the concentrations of some flavonoids at
      both sites, but seedlings at Oliver had significantly higher concentrations of
      flavonoids and chlorogenic acid than seedlings at Haliburton. We suggest that
      this could be associated with increased mobilization of Mn due to increased soil
      acidity, which interferes with the role of calcium (Ca) in the phenolic
      biosynthetic pathway. It appears that the composition of the forest soil governs
      the response of seedlings when they are exposed to abiotic stressors.

PMID- 16815838
TI  - Carbon dioxide exchange of larch (Larix gmelinii) cones during development.
AB  - Larch (Larix gmelinii (Rupr.) Rupr.) cone scales are green, but little is known
      of their photosynthetic role in cone development or about how they differ in gas
      exchange characteristics from needle leaves. In contrast to leaf photosynthesis
      (Pleaf), we found that stomatal regulation of cone photosynthetic rate (Pcone)
      was marginal because the photosynthetic carbon came from internal recycling of
      respiratory carbon dioxide (CO2). Photosynthetic recycling of respired CO2 was
      confirmed by the finding that the intercellular CO2 concentration (Ci) in cone
      scales was much higher than ambient [CO2]; also, there was a positive correlation
      between Pcone and Ci, whereas Pleaf was almost constant as Ci varied. Low
      chlorophyll (Chl) concentration was a limiting factor for Pcone, but not for
      Pleaf, as indicated by the correlation between Pcone and chlorophyll
      concentration. Moreover, chlorophyll utilization efficiency (Psat/Chl a+b) for
      cone scales was lower than that for leaves. In both cones and leaves, nitrogen
      (N) was positively correlated with photosynthetic capacity (P), but the P/N value
      was much lower for cones than for leaves. For both organs, the ratio of
      respiration to N was broadly similar. Although mature cones have no
      photosynthetic capacity, Pcone of young cones was as high as 5.3 micromol m(-2)
      s(-1), about 1.26 times the value of Pleaf, and accounted for the refixation of
      30-40% of the respiratory CO2 produced by cones, equivalent to the photosynthetic
      capacity of a bundle of short shoots near each cone. Thus, Pcone may be an
      important additional source of photosynthate for cones, given the weak
      assimilating capacity of leaves that are not fully expanded during cone
      development.

PMID- 16815839
TI  - Hormonal control of second flushing in Douglas-fir shoots.
AB  - Spring-flushing, over-wintered buds of Douglas-fir (Pseudotsuga menziesii (Mirb.)
      Franco) produce new buds that may follow various developmental pathways. These
      include second flushing in early summer or dormancy before flushing during the
      following spring. Second flushing usually entails an initial release of apical
      dominance as some of the current-season upper lateral buds grow out. Four
      hypotheses concerning control of current bud outgrowth in spring-flushing shoots
      were tested: (1) apically derived auxin in the terminal spring-flushing shoot
      suppresses lateral bud outgrowth (second flushing); (2) cytokinin (0.5 mM
      benzyladenine) spray treatments given midway through the spring flush period
      induce bud formation; (3) similar cytokinin spray treatments induce the outgrowth
      of existing current lateral buds; and (4) defoliation of the terminal spring
      flushing shoot promotes second flushing. Hypothesis 1 was supported by data
      demonstrating that decapitation-released apical dominance was completely restored
      by treatment with exogenous auxin (22.5 or 45 mM naphthalene acetic acid)
      (Thimann-Skoog test). Hypothesis 2 was marginally supported by a small, but
      significant increase in bud number; and Hypothesis 3 was strongly supported by a
      large increase in the number of outgrowing buds following cytokinin applications.
      Defoliation produced similar results to cytokinin application. We conclude that
      auxin and cytokinin play important repressive and promotive roles, respectively,
      in the control of second flushing in the terminal spring-flushing Douglas-fir
      shoot.

PMID- 16815840
TI  - Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization
      through selective inhibition of PHD2 expression.
AB  - The hypoxia-inducible transcription factor-1 (HIF-1) is central to a number of
      pathological processes through the induction of specific genes such as vascular
      endothelial growth factor (VEGF). Even though HIF-1 is highly regulated by
      cellular oxygen levels, other elements of the inflammatory and tumor
      microenvironment were shown to influence its activity under normal oxygen
      concentration. Among others, recent studies indicated that transforming growth
      factor (TGF) beta increases the expression of the regulatory HIF-1alpha subunit,
      and induces HIF-1 DNA binding activity. Here, we demonstrate that TGFbeta acts on
      HIF-1alpha accumulation and activity by increasing HIF-1alpha protein stability.
      In particular, we demonstrate that TGFbeta markedly and specifically decreases
      both mRNA and protein levels of a HIF-1alpha-associated prolyl hydroxylase (PHD),
      PHD2, through the Smad signaling pathway. As a consequence, the degradation of
      HIF-1alpha was inhibited as determined by impaired degradation of a reporter
      protein containing the HIF-1alpha oxygen-dependent degradation domain
      encompassing the PHD-targeted prolines. Moreover, inhibition of the TGFbeta1
      converting enzyme, furin, resulted in increased PHD2 expression, and decreased
      basal HIF-1alpha and VEGF levels, suggesting that endogenous production of
      bioactive TGFbeta1 efficiently regulates HIF-1-targeted genes. This was
      reinforced by results from HIF-1alpha knock-out or HIF-1alpha-inhibited cells
      that show impairment in VEGF production in response to TGFbeta. This study
      reveals a novel mechanism by which a growth factor controls HIF-1 stability, and
      thereby drives the expression of specific genes, through the regulation of PHD2
      levels.

PMID- 16815841
TI  - Engineering and characterization of a stabilized alpha1/alpha2 module of the
      class I major histocompatibility complex product Ld.
AB  - The major histocompatibility complex (MHC) is the most polymorphic locus known,
      with thousands of allelic variants. There is considerable interest in
      understanding the diversity of structures and peptide-binding features
      represented by this class of proteins. Although many MHC proteins have been
      crystallized, others have not been amenable to structural or biochemical studies
      due to problems with expression or stability. In the present study, yeast display
      was used to engineer stabilizing mutations into the class I MHC molecule, Ld. The
      approach was based on previous studies that showed surface levels of yeast
      displayed fusion proteins are directly correlated with protein stability. To
      engineer a more stable Ld, we selected Ld mutants with increased surface
      expression from randomly mutated yeast display libraries using anti-Ld antibodies
      or high affinity, soluble T-cell receptors (TCRs). The most stable Ld mutant, Ld
      m31, consisted of a single-chain MHC module containing only the alpha1 and alpha2
      domains. The enhanced stability was in part due to a single mutation (Trp-97 -->
      Arg), shown previously to be present in the allele Lq. Mutant Ld-m31 could bind
      to Ld peptides, and the specific peptide.Ld-m31 complex (QL9.Ld-m31) was
      recognized by alloreactive TCR 2C. A soluble form of the Ld-m31 protein was
      expressed in Escherichia coli and refolded from inclusion bodies at high yields.
      Surface plasmon resonance showed that TCRs bound to peptide.Ld-m31 complexes with
      affinities similar to those of native full-length Ld. The TCR and QL9.Ld-m31
      formed complexes that could be resolved by native gel electrophoresis, suggesting
      that stabilized alpha1/alpha2 class I platforms may enable various structural
      studies.

PMID- 16815842
TI  - ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional
      repression.
AB  - ErbB-4 is cleaved by alpha- and gamma-secretases to release a soluble 80-kDa
      intracellular domain, termed s80, which translocates to the nucleus. s80 is
      present in the nucleus of normal and cancerous mammary cells and is predicted to
      have a role in cell differentiation. To further investigate the mechanism by
      which s80 may mediate differentiation, we tested whether s80 regulates Eto2, a
      transcriptional corepressor that is involved in erythrocyte differentiation and
      is also implicated in human breast cancer. Here we show that ligand binding to
      ErbB-4 causes s80 translocation to the nucleus, where it colocalizes and
      interacts with Eto2. Expression of s80 blocks Eto2-mediated transcriptional
      repression of a heterologous promoter. This effect on Eto2 does not require s80
      kinase activity and is mediated by the carboxyl-terminal region of s80. Although
      other cell surface receptors regulate transcription by activating signal
      transduction cascades, these data present a novel mechanism of corepressor
      regulation and suggest a role for Eto2 in ErbB-4-dependent differentiation.

PMID- 16815843
TI  - Structural requirements for heparin/heparan sulfate binding to type V collagen.
AB  - Collagen-proteoglycan interactions participate in the regulation of matrix
      assembly and in cell-matrix interactions. We reported previously that a fragment
      (Ile824-Pro950) of the collagen alpha1(V) chain, HepV, binds to heparin via a
      cluster of three major basic residues, Arg912, Arg918, and Arg921, and two
      additional residues, Lys905 and Arg909 (Delacoux, F., Fichard, A., Cogne, S.,
      Garrone, R., and Ruggiero, F. (2000) J. Biol. Chem. 275, 29377-29382). Here, we
      further characterized the binding of HepV and collagen V to heparin and heparan
      sulfate by surface plasmon resonance assays. HepV bound to heparin and heparan
      sulfate with a similar affinity (KD approximately 18 and 36 nM, respectively) in
      a cation-dependent manner, and 2-O-sulfation of heparin was shown to be crucial
      for the binding. An octasaccharide of heparin and a decasaccharide of heparan
      sulfate were required for HepV binding. Studies with HepV mutants showed that the
      same basic residues were involved in the binding to heparin, to heparan sulfate,
      and to the cell surface. The contribution of Lys905 and Arg909 was found to be
      significant. The triple-helical peptide GPC(GPP)5G904-R918(GPP)5GPC-NH2 and
      native collagen V molecules formed much more stable complexes with heparin than
      HepV, and collagen V bound to heparin/heparan sulfate with a higher affinity (in
      the nanomolar range) than HepV. Heat and chemical denaturation strongly decreased
      the binding, indicating that the triple helix plays a major role in stabilizing
      the interaction with heparin. Collagen V and HepV may play different roles in
      cell-matrix interactions and in matrix assembly or remodeling mediated by their
      specific interactions with heparan sulfate.

PMID- 16815844
TI  - Effects of conducting and blocking ions on the structure and stability of the
      potassium channel KcsA.
AB  - This article reports on the interaction of conducting (K(+)) and blocking (Na(+))
      monovalent metal ions with detergent-solubilized and lipid-reconstituted forms of
      the K(+) channel KcsA. Monitoring of the protein intrinsic fluorescence reveals
      that the two ions bind competitively to KcsA with distinct affinities
      (dissociation constants for the KcsA.K(+) and KcsA.Na(+) complexes of
      approximately 8 and 190 mm, respectively) and induce different conformations of
      the ion-bound protein. The differences in binding affinity as well as the higher
      K(+) concentration bathing the intracellular mouth of the channel, through which
      the cations gain access to the protein binding sites, should favor that only
      KcsA.K(+) complexes are formed under physiological-like conditions. Nevertheless,
      despite such prediction, it was also found that concentrations of Na(+) well
      below its dissociation constant and even in the presence of higher K(+)
      concentrations, cause a remarkable decrease in the protein thermal stability and
      facilitate thermal dissociation into subunits of the tetrameric KcsA, as
      concluded from the temperature dependence of the protein infrared spectra and
      from gel electrophoresis, respectively. These latter observations cannot be
      explained based on the occupancy of the binding sites from above and suggest that
      there must be additional ion binding sites, whose occupancy could not be detected
      by fluorescence and in which the affinity for Na(+) must be higher or at least
      similar to that of K(+). Moreover, cation binding as reported by means of
      fluorescence does not suffice to explain the large differences in free energy of
      stabilization involved in the formation of the KcsA.Na(+) and KcsA.K(+)
      complexes, which for the most part should arise from synergistic effects of the
      ion-mediated intersubunit interactions.

PMID- 16815845
TI  - Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence
      lifetime imaging microscopy and a high-throughput fluorescent plate reader.
AB  - Presenilin 1 (PS1) in its active heterodimeric form is the catalytic center of
      the gamma-secretase complex, an enzymatic activity that cleaves amyloid precursor
      protein (APP) to produce amyloid beta (Abeta). Ubiquilin 1 is a recently
      described PS1 interacting protein, the overexpression of which increases PS1
      holoprotein levels and leads to reduced levels of functionally active PS1
      heterodimer. In addition, it has been suggested that splice variants of the
      UBQLN1 gene are associated with an increased risk of developing Alzheimer disease
      (AD). However, it is still unclear whether PS1 and ubiquilin 1 interact when
      expressed at endogenous levels under normal physiological conditions. Here, we
      employ three novel fluorescence resonance energy transfer-based techniques to
      investigate the interaction between PS1 and ubiquilin 1 in intact cells. We
      consistently find that the ubiquilin 1 N terminus is in close proximity to
      several epitopes on PS1. We show that ubiquilin 1 interacts both with PS1
      holoprotein and heterodimer and that the interaction between PS1 and ubiquilin 1
      takes place near the cell surface. Furthermore, we show that the PS1-ubiquilin 1
      interaction can be detected between endogenous proteins in primary neurons in
      vitro as well as in brain tissue of healthy controls and Alzheimer disease
      patients, providing evidence of its physiological relevance.

PMID- 16815846
TI  - The role of the S4-S5 linker and C-terminal tail in inositol 1,4,5-trisphosphate
      receptor function.
AB  - In previous studies we have suggested that spatial proximity of the C- and N
      terminal domains of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) may be
      critical for the channel gating mechanism. In the present study we have examined
      the sites of C-N interaction in more detail. We report that deletion mutations
      within the S4-S5 linker (amino acids 2418-2437) prevent co-immunoprecipitation of
      the C- and N-terminal domains, inhibit channel activity and enhance IP(3)
      binding. We also show that a region of the C-terminal tail (amino acids 2694
      2721), predicted to be a coiled-coil, is also required for channel activity.
      Circular dichroism spectroscopy and gel filtration studies confirm that this
      region has a helical structure with the ability to form tetramers. We propose a
      model in which IP(3)-induced conformational changes in the N-terminal domain are
      mechanically transmitted to the opening of the pore through an attachment to the
      S4-S5 linker. The coiled-coil domain in the C-terminal tail may play a critical
      role in maintaining the structural integrity of the channel.

PMID- 16815847
TI  - Peroxisome proliferator-activated receptor gamma promotes epithelial to
      mesenchymal transformation by Rho GTPase-dependent activation of ERK1/2.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) causes epithelial to
      mesenchymal transformation (EMT) in intestinal epithelial cells, as evidenced by
      reorganization of the actin cytoskeleton, acquisition of a polarized, mesenchymal
      cellular morphology, increased cellular motility, and colony scattering. This
      response is due to activation of Cdc42, resulting in p21-activated kinase
      dependent phosphorylation and activation of MEK1 Ser(298) and activation of
      ERK1/2. Dominant negative MEK1, MEK2, and ERK2 block PPARgamma-induced EMT,
      whereas constitutively active MEK1 and MEK2 induce a mesenchymal phenotype
      similar to that evoked by PPARgamma. PPARgamma also stimulates ERK1/2
      phosphorylation in the intestinal epithelium in vivo. PPARgamma induces the
      p110alpha subunit of phosphoinositide 3-kinase (PI3K), and inhibition of PI3K
      blocks PPARgamma-dependent phosphorylation of MEK1 Ser(298), activation of
      ERK1/2, and EMT. We conclude that PPARgamma regulates the motility of intestinal
      epithelial cells through a mitogen-activated protein kinase cascade that involves
      PI3K, Cdc42, p21-activated kinase, MEK1, and ERK1/2. Regulation of cellular
      motility through Rho family GTPases has not been previously reported for nuclear
      receptors, and elucidation of the mechanism that accounts for the role of
      PPARgamma in regulating motility of intestinal epithelial cells provides
      fundamental new insight into the function of this receptor during renewal of the
      intestinal epithelium.

PMID- 16815848
TI  - Mechanism of DNA recognition at a viral replication origin.
AB  - Recognition of the DNA origin by the Epstein-Barr nuclear antigen 1 (EBNA1)
      protein is the primary event in latentphase genome replication of the Epstein
      Barr virus, a model for replication initiation in eukaryotes. We carried out an
      extensive thermodynamic and kinetic characterization of the binding mechanism of
      the DNA binding domain of EBNA1, EBNA1452-641, to a DNA fragment containing a
      single specific origin site. The interaction displays a binding energy of 12.7
      kcal mol-1, with 11.9 kcal mol-1 coming from the enthalpic change with a minimal
      entropic contribution. Formation of the EBNA1452-641.DNA complex is accompanied
      by a heat capacity change of -1.22 kcal mol-1 K-1, a very large value considering
      the surface area buried, which we assign to an unusually apolar protein-DNA
      interface. Kinetic dissociation experiments, including fluorescence anisotropy
      and a continuous native electrophoretic mobility shift assay, confirmed that two
      EBNA1.DNA complex conformers are in slow equilibrium; one dissociates slowly
      (t1/2 approximately 41 min) through an undissociated intermediate species and the
      other corresponds to a fast twostep dissociation route (t1/2 approximately 0.8
      min). In line with this, at least two parallel association events from two
      populations of protein conformers are observed, with on-rates of 0.25-1.6x10(8) m
      1 s-1, which occur differentially either in excess protein or DNA molecules. Both
      parallel complexes undergo subsequent firstorder rearrangements of approximately
      2.0 s-1 to yield two consolidated complexes. These parallel association and
      dissociation routes likely allow additional flexible regulatory events for site
      recognition depending on site availability according to nucleus environmental
      conditions, which may lock a final recognition event, dissociate and re-bind, or
      slide along the DNA.

PMID- 16815851
TI  - Potential role of proliferation signal inhibitors on atherosclerosis in renal
      transplant patients.
AB  - Over the last decade, there has been a decrease in acute graft rejection rates
      following renal transplantation; however, this has not corresponded with an
      improvement in long-term outcomes of transplantation. One of the major causes of
      long-term morbidity and mortality in renal transplant recipients is
      cardiovascular disease. Immunosuppressive regimens, especially those including
      steroids and calcineurin inhibitors, have a negative role in the induction of
      cardiovascular risk factors. The proliferation signal inhibitors (PSIs)/mammalian
      target of rapamycin (mTOR) inhibitors sirolimus and everolimus have shown
      considerable promise in reducing acute rejection in renal transplant recipients.
      Although PSIs are associated with an increase in hyperlipidaemia
      (hypercholesterolaemia and hypertriglyceridaemia), which is a major risk factor
      for atherosclerosis and associated cardiovascular disease, recent studies with
      sirolimus have demonstrated protection from atheroma progression in
      hyperlipidaemic apolipoprotein E-deficient mice. Here, we summarize the results
      of pre-clinical and clinical studies with sirolimus and everolimus, with
      particular emphasis on the beneficial and adverse effects that these drugs exert
      on the cardiovascular system, and the underlying molecular mechanisms.

PMID- 16815849
TI  - Cyclin D3 expression in melanoma cells is regulated by adhesion-dependent
      phosphatidylinositol 3-kinase signaling and contributes to G1-S progression.
AB  - D-type cyclins regulate G1 cell cycle progression by enhancing the activities of
      cyclin-dependent kinases (CDKs), and their expression is frequently altered in
      malignant cells. We and others have previously shown that cyclin D1 is up
      regulated in melanoma cells through adhesion-independent MEK-ERK1/2 signaling
      initiated by mutant B-RAF. Here, we describe the regulation and role of cyclin D3
      in human melanoma cells. Cyclin D3 expression was enhanced in a cell panel of
      human melanoma cell lines compared with melanocytes and was regulated by
      fibronectin-mediated phosphatidylinositol 3-kinase/Akt signaling but not MEK
      activity. RNA interference experiments demonstrated that cyclin D3 contributed to
      G1-S cell cycle progression and proliferation in melanoma cells. Overexpression
      of cyclin D1 did not recover the effects of cyclin D3 knockdown. Finally,
      immunoprecipitation studies showed that CDK6 is a major binding partner for
      cyclin D3, whereas CDK4 preferentially associated with cyclin D1. Together, these
      findings demonstrate that cyclin D3 is an important regulator of melanoma G1-S
      cell cycle progression and that D-type cyclins are differentially regulated in
      melanoma cells.

PMID- 16815852
TI  - Everolimus in clinical practice--renal transplantation.
AB  - Everolimus is a proliferation signal inhibitor (PSI)/mammalian target of
      rapamycin inhibitor that is structurally similar to sirolimus, but with a number
      of important pharmacokinetic differences, including a shorter half-life and time
      to steady state. In clinical trials, the efficacy of everolimus 1.5 mg/day and
      3.0 mg/day combined with ciclosporin (CsA) and steroids in de novo renal
      transplant recipients is similar to that of mycophenolate mofetil, with one study
      showing a significantly lower risk of antibody-treated acute rejection with
      everolimus. When combined with reduced-dose CsA, everolimus is associated with
      improved renal function compared with full-dose CsA, with no decrease in
      efficacy. Thus, everolimus may play an important role in calcineurin inhibitor
      (CNI)-sparing regimens for renal transplant recipients. Studies with sirolimus
      have shown that CNI withdrawal is associated with a significant improvement in
      renal function, although there may be an increase in the risk of acute rejection.
      however, patient and graft survival are not adversely affected by CNI withdrawal.
      Notably, proteinuria <800 mg/day before conversion is a strong predictor of
      successful response to sirolimus treatment, and hypertensive therapy and serum
      lactate dehydrogenase levels may also predict response. Adverse events commonly
      associated with the PSIs include dyslipidaemia, proteinuria and anaemia, although
      these can usually be managed without difficulty. Data are also available to
      suggest that the PSIs are associated with a lower risk of malignancy than other
      immunosuppressive agents. In conclusion, everolimus may permit reduced exposure
      to CNIs in renal transplant recipients, with the potential to improve
      tolerability and renal function.

PMID- 16815853
TI  - Conversion to everolimus in maintenance patients--current clinical strategies.
AB  - Calcineurin inhibitors (CNIs) are associated with important side effects, such as
      nephrotoxicity, and thus there is an interest in developing CNI-sparing protocols
      using agents such as the proliferation signal inhibitor/mammalian target of
      rapamycin inhibitor everolimus. In a 3-month pilot study using an abrupt
      conversion protocol, ciclosporin (CsA) treatment was stopped after the morning
      dose and everolimus was started at 3.0 mg/day. Mycophenolic acid (MPA)-based
      therapy was continued, or prednisolone increased to 10 mg/day until target
      everolimus trough blood levels (3-8 ng/ml) were achieved. To date, seven patients
      have been enrolled, with three having completed at least 3 months of follow-up.
      Overall, conversion was effective and well-tolerated. Patients consistently
      achieved everolimus trough blood levels >3 ng/ml, and no episodes of acute
      rejection or proteinuria were reported after 3 months. In patients who completed
      the study, there were no major changes in the leucocyte or platelet counts during
      everolimus treatment. Serum creatinine levels were maintained or decreased
      slightly. One patient experienced a transient increase in serum creatinine during
      an episode of pneumonia, but levels decreased again after resolution of infection
      and temporary everolimus dose reduction. Serum cholesterol and triglyceride
      levels increased, but remained within acceptable limits. One patient receiving
      enteric-coated mycophenolate sodium 1440 mg/day experienced increasing everolimus
      trough blood levels and anaemia after conversion, and was therefore likely to
      have been over-immunosuppressed. Abrupt conversion to everolimus from CsA was
      effective and well-tolerated in renal transplant recipients. A reduction in MPA
      dosage at the time of conversion may be necessary to prevent over
      immunosuppression.

PMID- 16815854
TI  - Cardiovascular risk factors in renal transplantation--current controversies.
AB  - Cardiovascular diseases are more common in renal transplant recipients than in
      the general population, and a number of 'traditional' risk factors, such as
      smoking, diabetes mellitus and dyslipidaemia, are known to be associated with an
      increased risk. However, concentrating solely on these risk factors can lead to
      an underestimation of the true risk in this patient population, because other
      factors such as C-reactive protein and homocysteine levels are also associated
      with cardiovascular morbidity and mortality. Renal insufficiency also appears to
      be a key cardiovascular risk factor in the general population, with increasing
      proteinuria and decreasing glomerular filtration rate related to increased risk.
      In renal transplant recipients, a high proportion of whom have some renal
      insufficiency, the role of graft dysfunction in cardiovascular risk is
      controversial. While some studies have shown no correlation between graft
      dysfunction and congestive heart failure or ischaemic heart disease, registry
      data suggest that increased post-transplant serum creatinine levels are strongly
      associated with cardiovascular risk. This is believed to be the result of
      cardiovascular disease developing in the pre-transplantation period, as renal
      transplantation has been shown significantly to improve cardiovascular risk. As
      such, renal transplant recipients should be routinely screened for cardiovascular
      disease pre-transplantation, and immunosuppressive therapy should be tailored to
      minimize further risk. Different immunosuppressive agents, such as
      corticosteroids and calcineurin inhibitors, are associated with different
      exposure to cardiovascular risk, and studies involving withdrawal of these agents
      have generally shown improvement in parameters such as blood pressure and
      dyslipidaemia. However, these benefits are often associated with an increased
      incidence of acute rejection, although overall graft loss and mortality rates are
      not affected. Further studies are required to determine optimal regimens for
      minimizing cardiovascular risk in renal transplant recipients.

PMID- 16815855
TI  - Management of cardiovascular risk in patients receiving calcineurin inhibitors--a
      case report.
AB  - Cardiovascular disease is the main cause of death after renal transplantation.
      There are few trials evaluating the efficacy of prevention strategies in renal
      transplant patients on major adverse cardiac events (MACE) and cardiovascular
      mortality. However, there is general agreement that active prevention strategies
      can significantly decrease cardiovascular mortality after renal transplantation.
      Here, we present the case of a 52-year-old male patient who received a first
      kidney transplant in 1993. He showed a small fixed perfusion defect on thallium
      scintigraphy before transplant. He was admitted at 13 months due to an antero
      lateral myocardial infarction that was complicated with ventricular fibrillation.
      Despite anti-coagulation with acenocumarol, treatment with statins and
      angiotensin II receptor blocking agents and an excellent preservation of renal
      function, the patient presented with a second episode of myocardial infarction at
      9 years post-transplant. This case report is discussed in order to highlight the
      way in which attitudes have been modified in the past decade in order to
      systematically pursue an early diagnosis of pre-existing coronary artery disease,
      aggressively treat MACE and actively decrease cardiovascular risk in transplant
      patients, using all available efficacious treatments as well as individualizing
      immunosuppression to prolong not only graft but also patient survival.

PMID- 16815856
TI  - Conversion to a proliferation signal inhibitor in a patient with coronary artery
      disease--a case report.
AB  - The calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus are currently
      an important part of immunosuppressive regimens, but are associated with
      increased cardiovascular risk factors, including hyperlipidaemia, hypertension
      and diabetes mellitus. Conversion from CNI-based regimens to proliferation signal
      inhibitors or mammalian target of rapamycin inhibitors, such as everolimus and
      sirolimus, has been associated with an improvement in cardiovascular risk. This
      case study describes a 59-year-old renal transplant recipient who presented with
      angina pectoris while receiving immunosuppression with CsA, azathioprine and
      steroids. The patient developed angina pectoris 5 years after receiving a
      cadaveric renal transplant. At the time, the patient was obese, with hypertension
      controlled with diuretics and calcium channel blockers, and hyperlipidaemia
      controlled with statins. A scintigram revealed plurisegmental myocardial
      ischaemia, and a coronary angiogram showed the presence of occlusions in the left
      anterior descending artery and circumflex coronary artery. The patient also had
      70% stenosis of the right coronary artery, which was corrected by angioplastic
      percutaneous intervention. The patient was converted from azathioprine to
      sirolimus 2 mg/day (trough blood level, 6-10 ng/ml), while the CsA dose was
      tapered and withdrawn. The angina pectoris subsequently resolved, no progression
      of coronary artery disease (CAD) has been observed during follow-up and stable
      renal function has been maintained throughout. Conversion to an immunosuppressive
      regimen of sirolimus with CsA withdrawal, along with angioplastic percutaneous
      correction of right coronary artery stenosis, therefore led to the complete
      resolution of angina pectoris and no progression of the CAD was noticed in this
      obese renal transplant patient with drug-controlled hypertension and
      hyperlipidaemia.

PMID- 16815857
TI  - Conversion to everolimus in a patient with arterial hypertension and recurrent
      cutaneous neoplasia--a case report.
AB  - Calcineurin inhibitors (CNIs) are frequently associated with side effects such as
      nephrotoxicity and hypertension, so CNI withdrawal from immunosuppressive
      regimens is desirable in certain cases. The proliferation signal
      inhibitors/mammalian target of rapamycin inhibitors everolimus and sirolimus may
      play an important role in achieving CNI withdrawal. Studies on sirolimus have
      shown that conversion from CNIs is associated with improvements in renal function
      and hypertension. A case report is presented of a renal transplant recipient who
      experienced hypertension and recurrent cutaneous neoplasia while receiving a
      ciclosporin (CsA)-based immunosuppressive regimen. After transplantation, the
      patient received full-dose CsA and prednisolone. After 7 years, the patient's
      serum creatinine increased from 1.9 mg/dl to 2.5 mg/dl, and mycophenolate mofetil
      (MMF, 1000 mg/day) was introduced, enabling the CsA dose to be reduced to 100 mg
      b.i.d. The patient also required resection of five cutaneous neoplastic lesions;
      this led to the decision to stop CsA and start treatment with everolimus 1.5
      mg/day, which was increased to 3.0 mg/day to achieve target trough blood levels
      of 3 ng/ml. To avoid over-immunosuppression, the MMF dose was reduced to 500
      mg/day. After conversion, the patient experienced a substantial improvement in
      blood pressure, from 175/85 mmHg to 155/70 mmHg. Serum creatinine levels
      decreased to 1.6 mg/dl, and there has been no recurrence of cutaneous neoplasia
      in 9 months of follow-up. Therefore, conversion to everolimus from CsA in a renal
      transplant recipient led to improvements in blood pressure and resolution of
      recurrent cutaneous neoplasia, with no evidence of rejection or changes in renal
      function.

PMID- 16815858
TI  - Long-term cardiovascular risk in transplantation--insights from the use of
      everolimus in heart transplantation.
AB  - Everolimus is a potent immunosuppressive agent that has anti-proliferative
      activity. The benefits of everolimus vs azathioprine in de novo heart transplant
      recipients were assessed in a randomized, double-blind study. Patients (n = 634)
      were randomized to receive everolimus (1.5 mg/day or 3.0 mg/day) or azathioprine;
      all patients received steroids and full-dose ciclosporin (CsA). The primary
      endpoint was the incidence of efficacy failure [biopsy-proven acute rejection
      (BPAR), graft loss, death or loss to follow-up]. The incidence of cardiac
      allograft vasculopathy (CAV) was assessed by intravascular ultrasound. The
      incidence and hospitalization costs of major adverse cardiac events (MACE) were
      assessed after 4 years. The incidence of efficacy failure was significantly
      reduced with everolimus compared with azathioprine at 12, 24 and 48 months (P <
      0.05), largely because of a lower incidence of BPAR. An increase in serum
      creatinine levels was seen with everolimus compared with azathioprine, likely
      attributed to CsA nephrotoxicity. There was a significantly larger increase in
      vascular intimal thickness with azathioprine than with everolimus (P <or= 0.01),
      which was accompanied by a significantly lower incidence of CAV in the everolimus
      groups. After 4 years, the incidence of MACE was higher with azathioprine than
      with either dose of everolimus. MACE-related treatment costs were estimated at
      431,428 dollars for azathioprine, 136,664 dollars for everolimus 1.5 mg/day (68%
      saving) and 191,957 dollars for everolimus 3.0 mg/day (56% saving). Everolimus is
      significantly more effective than azathioprine in preventing efficacy failure in
      de novo heart transplant recipients and is also associated with reduced incidence
      and severity of CAV and MACE at 4 years post-transplant. The reduced 4-year
      incidence of MACE is likely to lead to substantially reduced hospitalization
      costs. Since cardiovascular morbidity and mortality are important factors in the
      long-term survival of renal transplant recipients, applying lessons from the use
      of everolimus in heart transplantation may further improve the understanding of
      managing cardiovascular risk in renal transplantation.

PMID- 16815859
TI  - Spliced isoforms of LIM-domain-binding protein (CLIM/NLI/Ldb) lacking the LIM
      interaction domain.
AB  - LIM-domain-binding proteins (CLIM/NLI/Ldb) are nuclear cofactors for LIM
      homeodomain transcription factors (LIM-HDs) and LIM-only proteins (LMOs). The LIM
      interaction domain (LID) of Ldb is located in the carboxy-terminal region and
      encoded by the last exon (exon 10) of Ldb genes. It is known that the mammalian
      CLIM1/Ldb2 gene has a splice isoform, named CLIM1b, lacking the LID. However,
      little is known about the nature of CLIM1b or the evolutionary conservation of
      this type of alternative splicing in amphibians and teleost fish. Here, we
      demonstrate that splice isoforms lacking the LID are also present in the Ldb1
      genes of mammals, chick, and Xenopus, as well as in fish paralog Ldb4. All these
      splicing variations occur in intron 9 and exon 10. We observed that Ldb4b (splice
      isoform lacking LID) is localized in the nucleus when expressed in mammalian
      culture cells, and binds to Ldb4a (splice isoform containing LID) but not
      directly to LIM proteins. However, Ldb4b binds to LMO4 via Ldb4a when coexpressed
      in culture cells. We also found that mouse Ldb1b lacks the ability to activate
      protein 4.2 promoter, which is stimulated by LMO2 and Ldb1. These findings
      suggest that splice isoforms of Ldb lacking LID are potential regulators of Ldb
      function.

PMID- 16815860
TI  - Myoclonus, motor deficits, alterations in emotional responses and monoamine
      metabolism in epsilon-sarcoglycan deficient mice.
AB  - Mutations of epsilon-sarcoglycan gene (SGCE) have been implicated in myoclonus
      dystonia (M-D), a movement disorder. To determine the pathophysiology of M-D, we
      produced Sgce knockout mice and found that the knockout mice exhibited myoclonus,
      motor impairments, hyperactivity, anxiety, depression, significantly higher
      levels of striatal dopamine and its metabolites, and an inverse correlation
      between the dopamine and serotonin metabolites. The results suggest that the
      diverse symptoms associated with M-D are indeed resulted from a single SGCE gene
      mutation that leads to alterations of dopaminergic and serotonergic systems.
      Therefore, antipsychotic agents and serotonin reuptake inhibitors may offer
      potential benefits for M-D patients.

PMID- 16815861
TI  - Quantitative determination of steroid hormone receptor positive cells in the
      synovium of patients with rheumatoid arthritis and osteoarthritis: is there a
      link to inflammation?
AB  - BACKGROUND: Steroid hormone receptors such as glucocorticoid receptors, androgen
      receptors, and oestrogen receptors alpha (ERalpha) and beta (ERbeta) have been
      identified in synovial cells of patients with rheumatoid arthritis and
      osteoarthritis. OBJECTIVES: To find a quantitative relationship between the
      number of receptor positive cells and markers of inflammation, and to compare the
      two groups of patients with rheumatoid arthritis and osteoarthritis. METHODS: A
      total of 36 patients with rheumatoid arthritis (n = 17) and osteoarthritis (n =
      19) were included, and receptor positive cells and cellular markers of synovial
      inflammation were quantified by immunohistochemistry and ELISA (interleukin 6
      (IL6) and IL8). RESULTS: Patients with rheumatoid arthritis showed a higher
      degree of histologically determined inflammation compared with those with
      osteoarthritis. However, synovial density of gluco-corticoid receptor positive
      (GR+), androgen receptor positive (AR+), ERalpha+ and ERbeta+ cells were not
      different among patients with rheumatoid arthritis and osteoarthritis. In
      patients with osteoarthritis, the density of GR+ cells positively correlated with
      the density of AR+, ERalpha+ and ERbeta+ cells (p = 0.007), which was not
      observed in patients with rheumatoid arthritis. This indicates positively coupled
      steroid hormone receptor expression in patients with osteoarthritis but not in
      those with rheumatoid arthritis. In patients with rheumatoid arthritis, secretion
      of synovial IL6 and IL8 positively correlated with the density of ERalpha+ and
      ERbeta+ cells (not with gluco-corticoid receptor and androgen receptor), which
      was not found in the synovium of patients with osteoarthritis. This indicates
      that inflammatory factors might up regulate the expression of oestrogen receptors
      in patients with rheumatoid arthritis, or vice versa. CONCLUSIONS: In patients
      with osteoarthritis, expression of different steroid receptors is positively
      coupled, which was not observed in the synovium of patients with rheumatoid
      arthritis. This uncoupling phenomenon in rheumatoid arthritis might lead to an
      imbalance of the normal synovial homeostasis.

PMID- 16815862
TI  - Systemic lupus erythematosus in a multiethnic US cohort LUMINA (XLI): factors
      predictive of self-reported work disability.
AB  - OBJECTIVE: To examine the risk factors for self-reported work disability in
      patients from the LUpus in MInorities: NAture vs. Nurture cohort with systemic
      lupus erythematosus (SLE). METHODS: Patients with SLE of Hispanic (Texas and
      Puerto Rico), African American and Caucasian ethnicity were studied. Work
      disability was defined by patients' self-report. Only patients known to be
      employed at the baseline visit were included. The probabilities of self-reporting
      work disability over time were examined by the Kaplan-Meier method; differences
      between ethnic groups were examined by the log-rank test. The relationship of
      baseline socioeconomic-demographic, clinical, behavioural and psychological
      features with work disability was examined by standard statistical tests.
      Variables with p<or=0.10 in these analyses were examined by logistic regression.
      RESULTS: The rate of self-reported work disability among the 273 patients studied
      was 19% at 5 years; it was numerically higher for the African Americans (25%)
      than for the Hispanics from Texas (19%) and the Caucasians (18%). The rate for
      the Hispanics from Puerto Rico was 7% at 2 years; 5-year rates could not be
      estimated for this ethnic subgroup (shorter follow-up in the cohort). In the
      regression analysis, age, male sex, poverty, total disease duration, disease
      activity and damage accrual were predictors of work disability. CONCLUSIONS: The
      rate of work disability was 19% at 5 years. Patients with SLE with more severe
      disease and with lower socioeconomic status are at high risk of becoming
      disabled. The toll SLE imposes could possibly be reduced in patients at risk if,
      in addition to medical treatment, services needed to overcome their
      disadvantageous socioeconomic status are provided.

PMID- 16815863
TI  - Anti-proteasome autoantibodies contribute to anti-nuclear antibody patterns on
      human larynx carcinoma cells.
AB  - BACKGROUND: Autoantibodies to the 20S proteasome represent an unspecific but
      common serological phenomenon in patients with systemic autoimmune diseases.
      Interestingly, a high prevalence of these antibodies have been observed in
      patients with connective tissue diseases, where anti-nuclear antibodies (ANAs)
      serve as an important diagnostic screening test. OBJECTIVE: To disclose
      interference of anti-proteasome antibodies with known ANA patterns. METHODS: Anti
      proteasome antibodies were isolated for comprehensive immunofluorescence
      analyses. The immunofluorescence pattern of human anti-proteasome antibodies was
      compared with a panel of monoclonal and polyclonal reference antibodies, and
      colocalisation was analysed using confocal microscopy. RESULTS: Anti-proteasome
      antibodies clearly contributed to the ANA patterns of their respective serum
      samples from patients with different rheumatic disorders. In addition to the
      nuclear pattern, proteasomal staining was also detectable in the cytoplasm, at
      the endoplasmic reticulum and perinuclear regions showing features overlapping
      with other known autoantibodies such as those to mitochondria. The specificity of
      anti-proteasome antibodies was proved by competition experiments and by
      colocalisation with monoclonal reference antibodies in confocal microscopy.
      CONCLUSION: In ANA diagnostics, interference of anti-proteasome antibodies will
      have to be taken into account, especially in the differentiation of anti
      cytoplasmatic autoantibodies.

PMID- 16815864
TI  - A prospective randomised multicentre study comparing continuous and intermittent
      treatment with celecoxib in patients with osteoarthritis of the knee or hip.
AB  - OBJECTIVE: To compare the effects of continuous and intermittent celecoxib
      treatment in patients with knee or hip osteoarthritis in flare. METHODS: In this
      24-week, prospective, randomised, double-blind, placebo-controlled study,
      patients were randomly assigned to receive continuous (n = 62) or intermittent (n
      = 61) treatment with celecoxib 200 mg once daily. The primary efficacy end point
      was the area under the curve (AUC) of the change in the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) total scores between baseline
      and week 24 divided by the time interval. Secondary end points included the
      percentage of days with intake of the flare drug, the AUC of the change in the
      WOMAC total scores, the mean change from baseline in the WOMAC scores, and the
      patient's and physician's global assessment of osteoarthritis. RESULTS: There
      were no significant differences between patients randomised to continuous or
      intermittent treatment in the primary end point or most of the secondary end
      points, although a consistent trend supporting continuous treatment was observed.
      The percentage of days with intake of the flare drug was significantly lower (p =
      0.031) in the group receiving continuous versus intermittent celecoxib. Both
      treatment regimens were well tolerated. CONCLUSION: The results of this pilot
      study indicate a potential clinical difference between continuous and
      intermittent treatment with celecoxib, and may be useful in designing future
      trials. A larger trial on both efficacy and safety outcomes is required for
      conclusive evidence in favour of either continuous or intermittent treatment.

PMID- 16815865
TI  - Serum tumor markers in skeletal metastasis.
AB  - BACKGROUND: There have been no well-documented reports detailing the relationship
      between skeletal metastasis and tumor markers in a large series of patients. The
      purpose of our study was to assess the relationship between the clinical features
      of skeletal metastasis and serum tumor markers and to determine whether tumor
      markers are a useful modality in the differential diagnosis of skeletal
      metastasis. METHODS: We retrospectively reviewed consecutive 458 patients with
      skeletal metastasis and divided the patients into two groups according to six
      clinical presenting factors. We assessed whether these groups influenced the
      level of the tumor markers in univariate and multivariate analysis. RESULTS:
      Patients with skeletal metastasis of carcinoma had a higher level of markers CEA
      (P < 0.0001) and CA19-9 (P = 0.0008) than patients with primary bone tumors and
      hematological malignancies. Univariate analysis of clinical variables revealed
      that metastasis on axial skeleton, multiple skeletal metastases and visceral
      metastasis were associated with the serum CEA and CA19-9 levels. By multivariate
      analysis, metastasis on axial skeleton, multiple skeletal metastases and visceral
      metastasis were found to be associated with the serum CEA and CA19-9 levels. At
      least one of the tumor markers was elevated in 73% of all patients. CONCLUSIONS:
      The higher tumor marker level (CEA, CA19-9) is predictive of metastasis on the
      axial skeleton, multiple skeletal metastases and visceral metastasis. Tumor
      markers are useful as a screening test to distinguish skeletal metastases of
      carcinoma from primary bone tumors or hematological malignancy from primary bone
      tumor and hematological malignancy.

PMID- 16815866
TI  - A novel mechanism of allosteric regulation of archaeal phosphoenolpyruvate
      carboxylase: a combined approach to structure-based alignment and model
      assessment.
AB  - Phosphoenolpyruvate carboxylase (PEPC) catalyzes the irreversible carboxylation
      of phosphoenolpyruvate (PEP) and plays a crucial role in fixing atmospheric CO(2)
      in C(4) and CAM plants. The enzyme is widespread in plants and bacteria and
      mostly regulated allosterically by both positive and negative effectors. Archaeal
      PEPCs (A-PEPCs) have unique characteristics in allosteric regulation and
      molecular mass, distinct from their bacterial and eukaryote homologues, and their
      amino acid sequences have become available only recently. In this paper, we
      generated a structure-based alignment of archaeal, bacterial and eukaryote PEPCs
      and built comparative models using a combination of fold recognition, sequence
      and structural analysis tools. Our comparative modeling analysis identified A
      PEPC-specific strong interactions between the two loops involved in both
      allostery and catalysis, which explained why A-PEPC is not influenced by any
      allosteric activators. We also found that the side-chain located three residues
      before the C-terminus appears to play a key role in determining the sensitivity
      to allosteric inhibitors. In addition to these unique features, we revealed how
      archaeal, bacterial and eukaryote PEPCs would share a common catalytic mechanism
      and adopt a similar mode of tetramer formation, despite their divergent
      sequences. Our novel observations will help design more efficient molecules for
      ecological and industrial use.

PMID- 16815867
TI  - A role for nitric oxide-mediated peroxynitrite formation in a model of endotoxin
      induced shock.
AB  - The aim of the present study was to assess the relative contributions of
      peroxynitrite formation following induction of nitric-oxide synthase (iNOS) in
      the pathophysiology of endotoxin-induced shock in the rat. To this end, we used a
      selective inhibitor of iNOS, N-(3-(aminomethyl)benzyl)acetamidine (1400W), and a
      peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphyrinato iron III chloride (FeTTPs). Intravenous (i.v.)
      administration of Escherichia coli lipopolysaccharide (LPS; 4 mg/kg) elicited a
      time-dependent fall in mean arterial pressure as well as liver, renal, and
      pancreatic tissue damage. 1400W (3-10 mg/kg i.v.) administered 30 min before LPS
      delayed the development of hypotension but did not improve survival. On the other
      hand, FeTTPs administered (10-100 mg/kg i.v.) inhibited in a dose-dependent
      manner LPS-induced hypotension, tissue injury, and improved mortality rate. In
      separate experiments, rats were treated with LPS (4 mg/kg) or saline for control,
      and their aortas were isolated and placed in organ baths 2 h later. Tissues from
      LPS-treated rats had significant inhibition of contractile activity to
      phenylephrine as well as a significantly impaired relaxation response to
      acetylcholine. FeTPPs, when administered (100 mg/kg i.v.) 1 h before LPS,
      prevented the LPS-induced aortic contractile and endothelial dysfunction. These
      results demonstrate that nitric oxide-derived peroxynitrite formation plays an
      important role in this model of endotoxemia. Our results also suggest that use of
      an iNOS inhibitor in this setting has little beneficial effect in part because,
      in the presence of a failing eNOS system, some NO is needed to maintain adequate
      organ function.

PMID- 16815868
TI  - Interaction of riluzole with the closed inactivated state of Kv4.3 channels.
AB  - The effect of riluzole on Kv4.3 was examined using the whole-cell patch-clamp
      technique. Riluzole inhibited the peak amplitude of Kv4.3 in a reversible,
      concentration-dependent manner with an IC(50) of 115.6 microM. Under control
      conditions, a good fit for the inactivation of Kv4.3 currents to a double
      exponential function, with the time constants of the fast component (tau(f)) and
      the slow component (tau(s)), was obtained. tau(f) was not altered by riluzole at
      concentrations up to 100 microM, but tau(s) became slower with increasing
      riluzole concentration, resulting in the crossover of the currents. The
      inhibition increased steeply with increasing channel activation at more positive
      potentials. In the full activation voltage range positive to (+)30 mV, however,
      no voltage-dependent inhibition was found. Riluzole shifted the voltage
      dependence of the steady-state inactivation of Kv4.3 in the hyperpolarizing
      direction in a concentration-dependent manner. However, the slope factor was not
      affected by riluzole. The K(i) for riluzole for interacting with the inactivated
      state of Kv4.3 was estimated from the concentration-dependent shift in the steady
      state inactivation curve and was determined to be 1.2 muM. Under control
      conditions, closed state inactivation was fitted to a single exponential
      function. Riluzole caused a substantial acceleration in the closed state
      inactivation. In the presence of riluzole, the recovery from inactivation was
      slower than under control conditions. Riluzole induced a significant use
      dependent inhibition of Kv4.3. These results suggest that riluzole inhibits Kv4.3
      by binding to the closed inactivated state of the channels and that the unbinding
      of riluzole occurs from the closed state during depolarization.

PMID- 16815869
TI  - Role of renal nerves and salt intake on erythropoietin secretion in rats
      following carbon monoxide exposure.
AB  - Because the data from the literature contain conflicting results regarding the
      role of renal nerves and angiotensin II in hypoxia-induced erythropoietin (EPO)
      secretion, we evaluated the effect of renal nerves and salt intake in rats on EPO
      secretion stimulated by carbon monoxide (CO). Serum levels and renal mRNA content
      of EPO were similarly elevated by exposure to different CO concentrations in a
      dose-dependent manner in rats with bilateral renal denervation (DNX) and in sham
      denervated controls (INN). However, at 600 ppm CO, serum concentrations and mRNA
      of EPO were significantly higher in DNX compared with INN rats (p < 0.05). This
      increase of EPO secretion in DNX rats could be blocked by administration of
      neuropeptide Y (NPY) (p < 0.05), whereas the NPY receptor antagonist did not
      enhance EPO secretion in INN rats after CO exposure. Agonists and antagonists of
      beta-adrenergic receptors had no effect on EPO secretion. High-salt (HS) diet
      reduced EPO secretory response at 600 ppm CO by 55% compared with INN rats on
      normal salt diet (p < 0.01). In addition, DNX increased EPO secretion in rats on
      low-salt and HS diet, whereas plasma renin activity did not correlate with EPO
      levels under these experimental conditions. In summary, our data suggest that
      renal nerves contribute to the half-maximal EPO secretory response to CO
      exposure, possibly via NPY receptors.

PMID- 16815870
TI  - Glucocerebroside ameliorates the metabolic syndrome in OB/OB mice.
AB  - Glucocerebroside (GC) is a naturally occurring glycolipid that may alter natural
      killer T (NKT) cell function. To determine the effect of GC on the metabolic
      derangements and immune profile in leptin-deficient mice, Ob/Ob mice were treated
      by daily injections of GC for 8 weeks and followed for various metabolic and
      immunological parameters. Marked amelioration of the metabolic alterations
      characteristic of leptin-deficient mice was observed in GC-treated animals
      compared with controls. A significant decrease in liver size and hepatic fat
      content were observed in GC-treated mice. Near-normalization of glucose tolerance
      and decreased serum triglyceride levels were observed. Fluorescence-activated
      cell sorting analysis of peripheral and intrahepatic lymphocytes revealed a 1.6
      fold increase of the peripheral/intrahepatic NKT lymphocyte ratio. A 33% decrease
      of serum interferon-gamma level and a 2.6-fold increase of serum interleukin 10
      level were noted in GC-treated mice. Immune modulation by GC may have a role in
      the treatment of nonalcoholic steatohepatitis and other immune-mediated
      disorders.

PMID- 16815871
TI  - A mechanistic study on reduced toxicity of irinotecan by coadministered
      thalidomide, a tumor necrosis factor-alpha inhibitor.
AB  - Dose-limiting diarrhea and myelosuppression compromise the success of irinotecan
      (7-ethyl-10-[4-[1-piperidino]-1-piperidino]carbonyloxycamptothecin) (CPT-11)
      based chemotherapy. A recent pilot study indicates that thalidomide attenuates
      the toxicity of CPT-11 in cancer patients. This study aimed to investigate
      whether coadministered thalidomide modulated the toxicities of CPT-11 and the
      underlying mechanisms using several in vivo and in vitro models. Diarrhea,
      intestinal lesions, cytokine expression, and intestinal epithelial apoptosis were
      monitored. Coadministered thalidomide (100 mg/kg i.p. for 8 days) significantly
      attenuated body weight loss, myelosuppression, diarrhea, and intestinal
      histological lesions caused by CPT-11 (60 mg/kg i.v. for 4 days). This was
      accompanied by inhibition of tumor necrosis factor-alpha, interleukins 1 and 6
      and interferon-gamma, and intestinal epithelial apoptosis. Coadministered
      thalidomide also significantly increased the systemic exposure of CPT-11 but
      decreased that of SN-38 (7-ethyl-10-hydroxycampothecin). It significantly reduced
      the biliary excretion and cecal exposure of CPT-11, SN-38, and SN-38 glucuronide.
      Thalidomide hydrolytic products inhibited hydrolysis of CPT-11 in rat liver
      microsomes but not in primary rat hepatocytes. In addition, thalidomide and its
      major hydrolytic products, such as phthaloyl glutamic acid (PGA), increased the
      intracellular accumulation of CPT-11 and SN-38 in primary rat hepatocytes. They
      also significantly decreased the transport of CPT-11 and SN-38 in Caco-2 and
      parental MDCKII cells. Thalidomide and PGA also significantly inhibited P
      glycoprotein (PgP/MDR1), multidrug resistance-associated protein (MRP1)- and MRP2
      mediated CPT-11 and SN-38 transport in MDCKII cells. These results provide
      insights into the pharmacodynamic and pharmacokinetic mechanisms for the
      protective effects of thalidomide against CPT-11-induced intestinal toxicity.

PMID- 16815872
TI  - Neurological features of congenital fibrosis of the extraocular muscles type 2
      with mutations in PHOX2A.
AB  - Congenital fibrosis of the extraocular muscles type 2 (CFEOM2) is a complex
      strabismus syndrome that results from mutations in the homeodomain transcription
      factor PHOX2A. To define the clinical and neuroimaging features of patients with
      this autosomal recessive syndrome, we studied 15 patients with genetically
      defined CFEOM2. All patients underwent full neurological, neuro-ophthalmological
      and orthoptic assessments. Twelve patients had pupillary pharmacological testing
      and nine had 3.0 tesla MRI of the brain, brainstem and orbits. Patients were born
      with severe bilateral ptosis and exotropia with almost complete bilateral absence
      of adduction, elevation, depression and intorsion. Variable abduction was present
      prior to strabismus surgery in 14 patients, and central ocular motility reflexes
      (smooth pursuit, saccades, vestibulo-ocular reflex and optokinetic reflex) were
      intact except for convergence. Pupillary light and near reflexes were not
      present, but irises were anatomically normal and responded to pupillary
      pharmacology. Neuroimaging of brain and brainstem was remarkable for the
      anatomical absence of cranial nerve (CN) 3 and probably CN 4 bilaterally.
      Therefore, the CFEOM2 phenotype and neuroimaging are both consistent with the
      congenital absence of CNs 3 and 4. Additional features included presence of most
      central ocular motility reflexes, a central lack of pupillary responsiveness of
      uncertain aetiology and modest phenotypic variability that does not correlate
      with specific PHOX2A mutations. Clinical presentation, neuroimaging and Phox2a-/-
      animal models all support the concept that CFEOM2 is a primary neurogenic
      abnormality with secondary myopathic changes.

PMID- 16815873
TI  - Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET
      study.
AB  - Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of
      frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy
      (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR
      alpha4 or beta2 subunit, which together compose the main cerebral nAChR.
      Electrophysiological assessment using in vitro expression systems indicated a
      gain of function of the mutant receptors. However the precise mechanisms by which
      they contribute to the pathogenesis of a focal epilepsy remain obscure,
      especially since alpha4beta2 nAChRs are known to be widely distributed within the
      entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the
      alpha4beta2 nAChRs, allows the determination of the regional distribution and
      density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering
      a unique opportunity to investigate some in vivo consequences of the molecular
      defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients
      (from five families) bearing an identified mutation in nAChRs and in seven age
      matched non-smoking healthy volunteers using PET and [(18)F]-F-A-85380.
      Parametric images of volume of distribution (Vd) were generated as the ratio of
      tissue to plasma radioactivities. The images showed a clear difference in the
      pattern of the nAChR density in the brains of the patients compared to the
      healthy volunteers. Vd values revealed a significant increase (between 12 and
      21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the
      cerebellum when compared to control subjects. Statistical parametric mapping
      (SPM) was then used to better analyse subtle regional differences. This analysis
      confirmed clear regional differences between patients and controls: patients had
      increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum,
      but decreased nAChR density in the right dorsolateral prefrontal region. In five
      patients who underwent an additional [(18)F]-fluorodeoxyglucose (FDG) PET
      experiment, hypometabolism was observed in the neighbouring area of the right
      orbitofrontal cortex. The demonstration of a regional nAChR density decrease in
      the prefrontal cortex, despite the known distribution of these receptors
      throughout the cerebral cortex, is consistent with a focal epilepsy involving the
      frontal lobe. We also propose that the nAChR density increase in mesencephalon is
      involved in the pathophysiology of ADNFLE through the role of brainstem ascending
      cholinergic systems in arousal.

PMID- 16815874
TI  - Impact of frontal white matter lesions on performance monitoring: ERP evidence
      for cortical disconnection.
AB  - We examined the impact of discrete white matter lesions in the frontal lobes on
      event-related potential (ERP) correlates of performance monitoring. We tested the
      hypothesis that abnormal performance monitoring may result from injury to white
      matter without evidence of injury to grey matter in the frontal lobes. It was
      predicted that such lesions may result in disconnection of the lateral and medial
      frontal cortices. The close interaction of these two areas has been implicated in
      performance monitoring. Two fast-choice response tasks were administered to
      patients with MRI-confirmed frontal white matter lesions due to sickle cell
      disease (SCD) vasculopathy (n = 11; age = 11-23 years; 6 unilateral left lesions
      and 5 bilateral lesions) and two control groups: SCD patients without brain
      lesions and non-sickle cell sibling controls (n = 11 each). Stimulus-locked ERP
      components N2 and P3 were not significantly affected by presence of lesions. The
      difference between response-locked components to correct trials (correct-response
      negativity--CRN) and erroneous trials (error-related negativity--ERN) was
      diminished in patients with unilateral and bilateral frontal white matter
      lesions. This finding was due to a significantly attenuated ERN amplitude in
      lesion patients compared with both sibling and non-lesion control groups. These
      ERP findings were not due to performance differences between groups and hence
      reflect a compromised neural substrate underlying performance monitoring. The
      latter may also contribute to the deficits in executive function tasks observed
      in these patients. As disruption to ERP markers of error processing was found in
      the absence of lesions to the lateral or medial frontal cortex, we conclude that
      a functional connection between these areas facilitates performance monitoring,
      possibly implemented via tracts traversing the deep frontal white matter.

PMID- 16815875
TI  - Apparent diffusion coefficient measurements of the middle cerebellar peduncle
      differentiate the Parkinson variant of MSA from Parkinson's disease and
      progressive supranuclear palsy.
AB  - Clinical differentiation of parkinsonian syndromes such as the Parkinson variant
      of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) from
      Parkinson's disease is difficult in the early stage of the disease. In order to
      identify objective markers for differential diagnosis, we studied these three
      groups of patients with diffusion-weighted MRI (DWI). Sixteen MSA-P patients, 16
      with PSP, 16 with Parkinson's disease and 15 healthy volunteers were studied.
      Regional apparent diffusion coefficients (rADC) were determined in different
      brain regions including basal ganglia, thalamus, white matter, pons and middle
      cerebellar peduncles (MCPs). rADC calculated in the MCP completely differentiated
      MSA-P patients (median: 0.93 x 10(-3) mm2/s) from PSP patients (median: 0.82 x
      10(-3) mm2/s, P < 0.001), Parkinson's disease patients (median: 0.79 x 10(-3)
      mm2/s, P < 0.001) and healthy volunteers (median: 0.81 x 10(-3) mm2/s, P <
      0.001). Other regions considered showed an overlapping among groups. DWI
      discriminates MSA-P from PSP and Parkinson's disease and healthy volunteers on
      the basis of MCP rADC values. These in vivo results confirm the pathological
      findings that the majority of MSA-P patients have moderate or severe degenerative
      changes not only in the nigrostriatal but also in the olivopontocerebellar
      systems. Our findings indicate that, in order to substantially contribute to the
      in vivo differential diagnosis of MSA-P, PSP and Parkinson's disease, rADC
      measurements should not be limited to the basal ganglia but should also include
      the MCP.

PMID- 16815876
TI  - The vascular supply of the functional compartments of the human striatum.
AB  - The basal ganglia (BG) contain several functional compartments and multiple,
      parallel segregated circuits processing different cortical information through
      cortical-BG-thalamus-cortical loops. Three zones of corticostriatal input are
      present: sensorimotor, associative and limbic, which correspond to poor,
      intermediate and strong calbindin (CB) labelling, respectively. Other functional
      compartments, such as striosomes, extrastriosomal matrix and matrisomes, also
      convey segregated projections. Microvascular territories in the human BG are
      spatially consistent with little overlap and few anastomoses. A high percentage
      of lacunar infarcts occur in the BG, yet the relationship between lacunae and
      functional compartments is unknown. We determined the relationship between
      microvascular territories and functional compartments within the human striatum.
      Microvascular territories were labelled by co-injection of diffusible dye, radio
      opaque substance and gelatin into parental vessels and by sectioning each BG co
      planar with the Talairach system. Sections underwent immunocytochemistry or
      histochemistry and the overlap of microvascular and functional territories was
      examined. CB staining of the arterial-injected striatum matched the functional
      compartments reported previously and overlay of microvascular territories
      revealed a correspondence between (i) the lateral lenticulostriate arteries (LSA)
      and sensorimotor zone; (ii) the medial LSA and associative zone; and (iii) the
      recurrent artery of Heubner (RAH) and limbic zone. A greater number of large
      vessels and capillaries were found in the matrix compared to striosomes, and a
      likely correspondence exists between high-density arteriole envelopes and
      matrisomes. The higher number of non-anastomotic vessels and capillary beds
      within the matrix predisposes these regions to both large lesions and small
      lacunar infarcts, creating specific symptoms based on striatal circuitry.

PMID- 16815877
TI  - Aerobic training is safe and improves exercise capacity in patients with
      mitochondrial myopathy.
AB  - Exercise intolerance is a prominent symptom in patients with mitochondrial
      myopathy (MM), but it is still unsettled whether exercise training is safe and
      beneficial for patients with MM. To address this, we studied the effect of 12
      weeks cycle training on exercise capacity, quality of life and underlying
      molecular and cellular events in five patients with single large-scale deletions,
      one with a microdeletion and 14 with point mutations of mitochondrial DNA
      (mtDNA), and 13 healthy subjects. Each training session lasted 30 min, and was
      performed at an intensity of 70% of VO2max (maximal oxygen uptake). Each subject
      performed 50 training sessions in 12 weeks. All subjects were evaluated before
      and after training, and 13 MM patients were studied after 8 weeks of
      deconditioning. Evaluation included VO2max and mutation load and mtDNA quantity,
      mitochondrial enzymatic activity, and number of centrally nucleated, apoptotic,
      ragged red and cytochrome oxidase (COX)-negative fibres in muscle biopsies from
      the quadriceps muscle. After 12 weeks of training, VO2max and muscle citrate
      synthase increased in MM (26 and 67%) and healthy (17 and 65%) subjects, while
      mtDNA quantity in muscle only increased in the MM patients (81%). In the MM
      patients, training did not change mtDNA mutation load in muscle, mitochondrial
      enzyme complex activities, muscle morphology and plasma creatine kinase. After
      deconditioning, VO2max and citrate synthase activity returned to values before
      training, while muscle mtDNA mutation load decreased. These findings show that
      aerobic training efficiently improves oxidative capacity in MM patients. Based on
      unchanged levels of mutant load in muscle, morphological findings on muscle
      biopsy and plasma creatine kinase levels during training, the treatment appears
      to be safe. Regular, supervised aerobic exercise is therefore recommended in MM
      patients with the studied mutations.

PMID- 16815878
TI  - Semantic impairment in stroke aphasia versus semantic dementia: a case-series
      comparison.
AB  - Different neuropsychological populations implicate diverse cortical regions in
      semantic memory: semantic dementia (SD) is characterized by atrophy of the
      anterior temporal lobes whilst poor comprehension in stroke aphasia is associated
      with prefrontal or temporal-parietal infarcts. This study employed a case-series
      design to compare SD and comprehension-impaired stroke aphasic patients directly
      on the same battery of semantic tests. Although the two groups obtained broadly
      equivalent scores, they showed qualitatively different semantic deficits. The SD
      group showed strong correlations between different semantic tasks--regardless of
      input/output modality--and substantial consistency when a set of items was
      assessed several times. They were also highly sensitive to frequency/familiarity
      and made coordinate and superordinate semantic errors in picture naming. These
      findings support the notion that amodal semantic representations degrade in SD.
      The stroke aphasia group also showed multimodal deficits and consistency across
      different input modalities, but inconsistent performance on tasks requiring
      different types of semantic processing. They were insensitive to
      familiarity/frequency--instead, tests of semantic association were influenced by
      the ease with which relevant semantic relationships could be identified and
      distractors rejected. In addition, the aphasic patients made associative semantic
      errors in picture naming that SD patients did not make. The aphasic patients'
      picture naming performance improved considerably with phonemic cues suggesting
      that these patients retained knowledge that could not be accessed without
      contextual support. We propose that semantic cognition is supported by two
      interacting principal components: (i) a set of amodal representations (which
      progressively degrade in SD) and (ii) executive processes that help to direct and
      control semantic activation in a task-appropriate fashion (which are
      dysfunctional in comprehension-impaired stroke aphasic patients).

PMID- 16815879
TI  - Brain damage as detected by magnetization transfer imaging is less pronounced in
      benign than in early relapsing multiple sclerosis.
AB  - The trend to start disease-modifying therapy early in the course of multiple
      sclerosis makes it important to establish whether the benign form is a real
      entity. In previous studies, measures of magnetization transfer (MT) ratio (MTr)
      have been shown to provide good estimates of the amount of tissue damage
      occurring in multiple sclerosis brains. Thus, with the hypothesis that if benign
      multiple sclerosis patients were really benign, sensitive measures of subtle
      tissue damage would be less pronounced in these patients than in very early
      relapsing-remitting (RR) multiple sclerosis patients. We carried out conventional
      MRI and MT imaging in 50 patients with benign multiple sclerosis [defined as
      having Kurtzke Expanded Disability Status Score (EDSS) <3 and disease duration
      >15 years] and in 50 early RR patients selected to have similar disability (EDSS
      <3) and short disease duration (<3 years). Data were compared with those of 32
      demographically-matched normal controls. We used a fully automated procedure to
      measure lesional-MTr, perilesional-MTr, normal-appearing white matter (NAWM) MTr
      and cortical-MTr. We found that, after correction for common effects of age,
      lesional-MTr and perilesional-MTr of benign patients were significantly (P <
      0.0001) lower than WM of normal controls, but significantly (P < 0.0001) higher
      than corresponding tissues of RR patients. In NAWM and cortex, MTr values of
      benign patients were similar to those of normal controls (P > 0.5) and
      significantly higher than those of the RR patients (P < 0.0001 and P < 0.01,
      respectively). Similar differences in MTr measures between benign and RR patients
      were found when patient groups were selected to have no disability (EDSS < or =
      2) and, for benign multiple sclerosis, very long disease duration (>20 years) or
      when both groups were matched for high lesion load (T2-weighted lesion volume >10
      cm3). We conclude that lesional and non-lesional MTr values can be significantly
      less pronounced in benign multiple sclerosis than in a cohort of RR patients at
      their earliest disease stages, suggesting that brain tissue damage is milder in
      benign multiple sclerosis than in early RR disease. This can be due to an
      extraordinary beneficial response to demyelination of benign patients and may
      represent the evidence that benign multiple sclerosis truly exists and might be
      differentiated from other forms of this illness.

PMID- 16815880
TI  - Metoclopramide-induced hyperprolactinaemia caused marked decline in pinopodes and
      pregnancy rates in mice.
AB  - BACKGROUND: The impact of hyperprolactinaemia on endometrial function, along with
      embryo implantation, has been the subject of discussion. This article examines
      whether experimental hyperprolactinaemia can affect mouse ovarian function,
      endometrial pinopodes and embryo implantation. METHODS: For pinopode analysis, 60
      female mice were randomly divided into two groups: control (vehicle) and
      experimental [metoclopramide (MCP) 200 microg per day]. Injections were given
      subcutaneously for 50 days, and then, normally cycling females were housed with
      male mice for copulation during proestrus. The animals were killed on the fifth
      day following coitus when the antimesometrium portions of the uterine horns were
      removed for endometrial analysis. Blood was collected for prolactin (PRL)
      determination. In the second experiment, 60 female mice were used to evaluate the
      ovarian function by measuring estrogen and progesterone levels and counting
      luteal bodies and oocytes in the oviduct and uterus during estrus. RESULTS: The
      highest pregnancy rates and the largest population of pinopodes were both found
      in the vehicle group (P<0.01). Estrogen and progesterone levels in MCP-treated
      mice were lower than those in control mice (P<0.05). Also, the number of
      implantations was significantly lower in the MCP-treated group compared with the
      vehicle group after embryo transfer (P<0.001). CONCLUSION: PRL seems to have
      suppressive effects on ovarian function and the number of pinopodes; conceivably,
      hyperprolactinaemia has a negative effect on mouse embryo implantation.

PMID- 16815881
TI  - Escaping the tyranny of the embryo? A new approach to ART regulation based on UK
      and Australian experiences.
AB  - The early legislative responses to fertilization of human oocytes in vitro
      exaggerated the protection of the embryo at the expense of the interests of other
      parties. Although more recent legislative changes have lessened this embryonic
      grip, it nonetheless still distorts legal thinking and is fundamentally in
      conflict with biological understanding. Drawing largely on experiences in the UK
      and Australia, a proposal is explored that reframes the legislative approach to
      the regulation of assisted reproductive technology (ART) with the following
      objectives: (i) to align more closely the legal and biological understandings of
      the earliest stages of human development; (ii) to place the legislative focus on
      objective, intent and outcome; and in the process (iii) to disentangle legally
      and conceptually the status of the embryo from that of the potential child.
      Experiences in the UK and Australia are drawn on, because these two jurisdictions
      have a common legal heritage and were among the earliest players both
      scientifically and legally but have pursued very different legal routes to their
      current legislative practices.

PMID- 16815882
TI  - Case finding for patients at risk of readmission to hospital: development of
      algorithm to identify high risk patients.
AB  - OBJECTIVE: To develop a method of identifying patients at high risk of
      readmission to hospital in the next 12 months for practical use by primary care
      trusts and general practices in the NHS in England. DATA SOURCES: Data from
      hospital episode statistics showing all admissions in NHS trusts in England over
      five years, 1999-2000 to 2003-4; data from the 2001 census for England.
      Population All residents in England admitted to hospital in the previous four
      years with a subset of "reference" conditions for which improved management may
      help to prevent future admissions. DESIGN: Multivariate statistical analysis of
      routinely collected data to develop an algorithm to predict patients at highest
      risk of readmission in the next 12 months. The algorithm was developed by using a
      10% sample of hospital episode statistics data for all of England for the period
      indicated. The coefficients for 21 most powerful (and statistically significant)
      variables were then applied against a second 10% test sample to validate the
      findings of the algorithm from the first sample. RESULTS: The key factors
      predicting subsequent admission included age, sex, ethnicity, number of previous
      admissions, and clinical condition. The algorithm produces a risk score (from 0
      to 100) for each patient admitted with a reference condition. At a risk score
      threshold of 50, the algorithm identified 54.3% of patients admitted with a
      reference condition who would have an admission in the next 12 months; 34.7% of
      patients were "flagged" incorrectly (they would not have a subsequent admission).
      At risk score threshold levels of 70 and 80, the rate of incorrectly "flagged"
      patients dropped to 22.6% and 15.7%, but the algorithm found a lower percentage
      of patients who would be readmitted. The algorithm is made freely available to
      primary care trusts via a website. CONCLUSIONS: A method of predicting individual
      patients at highest risk of readmission to hospital in the next 12 months has
      been developed, which has a reasonable level of sensitivity and specificity.
      Using various assumptions a "business case" has been modelled to demonstrate to
      primary care trusts and practices the potential costs and impact of an
      intervention using the algorithm to reduce hospital admissions.

PMID- 16815883
TI  - Orthopaedic grade ultra-high molecular weight polyethylene: some features of the
      main thermoluminescence glow curve.
AB  - Thermoluminescence (TL) characteristics of orthopaedic-grade ultra-high molecular
      weight polyethylene have been investigated between 20 and 200 degrees C. The TL
      at 1 degrees C s(-1) consists of two glow curves, a weaker intensity peak at 115
      degrees C and the main peak at 70 degrees C, studied in this work. TL intensity
      increases with beta irradiation but with a dose-response influenced by heating
      rate. On the other hand, the peak maximum is affected by both irradiation and
      repeated use of a sample. The glow curve shifts to higher temperatures with
      increase in heating rate but only slightly so with change in beta irradiation
      dose, properties suggestive of first-order kinetics. Kinetic analysis for
      activation energy and order of kinetics, based on the discrete trap model,
      produce somewhat conflicting results. Whereas qualitative analysis of peak
      symmetry show that first-order kinetics apply, geometrical analysis of the peak
      shape suggests that the order of kinetics might be other than first-order. Values
      of activation energy evaluated using the initial rise method were found to be
      dose dependent and for a given beta dose are in agreement with calculations from
      peak shape and initial rise methods but less so with results from variable
      heating rate method.

PMID- 16815884
TI  - Natural background dose and radium equivalent measurements at Ikogosi warm
      spring, Nigeria.
AB  - The natural background dose and the radium equivalent due to the natural
      radioactivity levels in rocks and sediments collected around Ikogosi warm spring,
      Nigeria, has been determined in this study using a highly sensitive HpGe
      detector. The mean activity concentration of (40)K, (226)Ra and (228)Ac were
      measured to be 585.50 +/- 17.40 Bq kg(-1), 66.91 +/- 5.23 Bq kg(-1) and 48.91 +/-
      2.10 Bq kg(-1), respectively, in rock samples while in sediment samples the
      activity concentrations were found to be 113.89 +/- 5.64 Bq kg(-1) for (40)K,
      21.47 +/- 5.14 Bq kg(-1) for (226)Ra and 14.20 +/- 1.07 Bq kg(-1) for (228)Ac.
      This mean values give rise to average absorbed dose rate of 85.87 nGy h(-1) at a
      distance of 1.0 m above the ground level and a mean human effective dose
      equivalent of 0.53 man Sv y(-1) for rock samples. A radium equivalent of 50.55 Bq
      kg(-1) was measured for the sediment samples. The radium equivalent value is far
      less than the 370 Bq kg(-1) limit for materials that can be used as building
      materials while the human effective dose equivalent falls below the world average
      background dose of 2.4 man Sv y(-1).

PMID- 16815885
TI  - Monte Carlo simulation of scattered and thermal photoneutron fluences inside a
      radiotherapy room.
AB  - In this work, the behaviour of scattered and thermal photoneutron fluences in a
      radiotherapy treatment room was investigated by means of Monte Carlo simulation.
      The MCNP code was used to study the dependence of these neutron fluences on room
      design, room area and the effect of neutron moderator materials placed on the
      room walls. The results of the investigation showed a poor agreement between the
      simulations and empirical approximations, suggesting that the formulae found in
      the literature can underestimate the neutron flux inside a radiotherapy room.

PMID- 16815886
TI  - 3-Deazaadenosine mitigates arterial remodeling and hypertension in
      hyperhomocysteinemic mice.
AB  - Chronic hyperhomocysteinemia (HHcy) is an important factor in development of
      arterial hypertension. HHcy is associated with activation of matrix
      metalloproteinases (MMPs); however, it is unclear whether HHcy-dependent
      extracellular matrix (ECM) accumulation plays a role in arterial hypertrophy and
      hypertension. We tested the hypothesis that in HHcy the mechanism of arterial
      hypertension involves arterial dysfunction in response to ECM accumulation
      between endothelial and arterial smooth muscle cells and subsequent endothelium
      myocyte (E-M) uncoupling. To decrease plasma Hcy, dietary supplementation with 3
      deazaadenosine (DZA), the S-adenosylhomocysteine hydrolase inhibitor, was
      administered to cystathionine beta-synthase (CBS) knockout (KO) mice. Mice were
      grouped as follows: wild type (WT; control), WT+DZA, CBSKO, and CBSKO+DZA (n =
      4/group). Mean aortic blood pressure and heart rate were monitored in real time
      with a telemetric system before, during, and after DZA treatment (6 wk total). In
      vivo aorta function and morphology were analyzed by M-mode and Doppler
      echocardiography in anesthetized mice. Aorta MMP activity in unfixed cryostat
      sections was measured with DQ gelatin. Aorta MMP-2, MMP-9, and connexin 43
      expression were measured by RT-PCR and Western blot analyses, respectively. HHcy
      caused increased aortic blood pressure and resistance, tachycardia, and increased
      wall thickness and ECM accumulation in aortic wall vs. control groups. There was
      a linear correlation between aortic wall thickness and plasma Hcy levels. MMP-2,
      MMP-9, and connexin 43 expression were increased in HHcy. In the CBSKO+DZA group,
      aortic blood pressure and levels of MMP and connexin 43 were close to those found
      in control groups. However, removal of DZA reversed the aortic lumen-to-wall
      thickness ratio in CBSKO mice, suggesting, in part, a role of vascular remodeling
      in the increase in blood pressure in HHcy. The results show that arterial
      hypertension in HHcy mice is, in part, associated with arterial remodeling and E
      M uncoupling in response to MMP activation.

PMID- 16815887
TI  - Rho kinase activation maintains high pulmonary vascular resistance in the ovine
      fetal lung.
AB  - Mechanisms that maintain high pulmonary vascular resistance (PVR) in the fetal
      lung are poorly understood. Activation of the Rho kinase signal transduction
      pathway, which promotes actin-myosin interaction in vascular smooth muscle cells,
      is increased in the pulmonary circulation of adult animals with experimental
      pulmonary hypertension. However, the role of Rho kinase has not been studied in
      the fetal lung. We hypothesized that activation of Rho kinase contributes to
      elevated PVR in the fetus. To address this hypothesis, we studied the pulmonary
      hemodynamic effects of brief (10 min) intrapulmonary infusions of two specific
      Rho kinase inhibitors, Y-27632 (15-500 microg) and HA-1077 (500 microg), in
      chronically prepared late-gestation fetal lambs (n = 9). Y-27632 caused potent,
      dose-dependent pulmonary vasodilation, lowering PVR from 0.67 +/- 0.18 to 0.16 +/
      0.02 mmHg x ml(-1) x min(-1) (P < 0.01) at the highest dose tested without
      lowering systemic arterial pressure. Despite brief infusions, Y-27632-induced
      pulmonary vasodilation was sustained for 50 min. HA-1077 caused a similar fall in
      PVR, from 0.39 +/- 0.03 to 0.19 +/- 0.03 (P < 0.05). To study nitric oxide (NO)
      Rho kinase interactions in the fetal lung, we tested the effect of Rho kinase
      inhibition on pulmonary vasoconstriction caused by inhibition of endogenous NO
      production with nitro-L-arginine (L-NA; 15-30 mg), a selective NO synthase
      antagonist. L-NA increased PVR by 127 +/- 73% above baseline under control
      conditions, but this vasoconstrictor response was completely prevented by
      treatment with Y-27632 (P < 0.05). We conclude that the Rho kinase signal
      transduction pathway maintains high PVR in the normal fetal lung and that
      activation of the Rho kinase pathway mediates pulmonary vasoconstriction after NO
      synthase inhibition. We speculate that Rho kinase plays an essential role in the
      normal fetal pulmonary circulation and that Rho kinase inhibitors may provide
      novel therapy for neonatal pulmonary hypertension.

PMID- 16815888
TI  - Identification of a hydrogen peroxide-induced PP1-JNK1-Sp1 signaling pathway for
      gene regulation.
AB  - Oxidative stress often results in changes in gene expression through the
      regulation of transcription factors. In this study, we examine how Sp1
      phosphorylation is regulated by H(2)O(2) in a human alveolar epithelial cell line
      (HAE). Treatment of HAE cells with H(2)O(2) increases phosphorylation of Sp1 and
      activates JNK. To establish a relationship between JNK and Sp1, we show that JNK
      activator anisomycin increases Sp1 phosphorylation, and JNK inhibitors as well as
      dominant-negative JNK1 attenuate H(2)O(2)-induced Sp1 phosphorylation.
      Additionally, JNK1 directly phosphorylates Sp1 in vitro, reducing Sp1 binding to
      DNA. These results demonstrate the role of JNK in H(2)O(2)-induced Sp1
      phosphorylation. Because H(2)O(2) inhibits Ser/Thr protein phosphatase-1 (PP1),
      we examined the role of PP1 in the regulation of JNK. Similar to H(2)O(2),
      inhibition of PP1 induces phosphorylation of Sp1 and activation of JNK in HAE
      cells. Inhibition of JNK activity using either inhibitors or dominant-negative
      mutant JNK1 suppresses PP1 inhibition-induced Sp1 phosphorylation. Furthermore,
      PP1 directly inactivates JNK1 in vitro. These data suggest that 1) H(2)O(2)
      increases the phosphorylation level of Sp1, 2) Sp1 is a target of the JNK
      pathway, 3) PP1 regulates JNK activation, and 4) the "PP1-JNK" pathway plays a
      role in H(2)O(2)-induced Sp1 phosphorylation in lung epithelial cells.

PMID- 16815889
TI  - Bone morphogenetic protein-2 upregulates expression and function of voltage-gated
      K+ channels in human pulmonary artery smooth muscle cells.
AB  - Activity of voltage-gated K(+) (K(V)) channels in pulmonary artery smooth muscle
      cells (PASMC) plays an important role in control of apoptosis and proliferation
      in addition to regulating membrane potential and pulmonary vascular tone. Bone
      morphogenetic proteins (BMPs) inhibit proliferation and induce apoptosis in
      normal human PASMC, whereas dysfunctional BMP signaling and downregulated K(V)
      channels are involved in pulmonary vascular medial hypertrophy associated with
      pulmonary hypertension. This study evaluated the effect of BMP-2 on K(V) channel
      function and expression in normal human PASMC. BMP-2 (100 nM for 18-24 h)
      significantly (>2-fold) upregulated mRNA expression of KCNA5, KCNA7, KCNA10,
      KCNC3, KCNC4, KCNF1, KCNG3, KCNS1, and KCNS3 but downregulated (at least 2-fold)
      KCNAB1, KCNA2, KCNG2, and KCNV2. The most dramatic change was the >10-fold
      downregulation of KCNG2 and KCNV2, two electrically silent gamma-subunits that
      form heterotetramers with functional K(V) channel alpha-subunits (e.g., KCNB1-2).
      Furthermore, the amplitude and current density of whole cell K(V) currents were
      significantly increased in PASMC treated with BMP-2. It has been demonstrated
      that K(+) currents generated by KCNB1 and KCNG1 (or KCNG2) or KCNB1 and KCNV2
      heterotetramers are smaller than those generated by KCNB1 homotetramers,
      indicating that KCNG2 and KCNV2 (2 subunits that were markedly downregulated by
      BMP-2) are inhibitors of functional K(V) channels. These results suggest that BMP
      2 divergently regulates mRNA expression of various K(V) channel alpha-, beta-,
      and gamma-subunits and significantly increases whole cell K(V) currents in human
      PASMC. Finally, we present evidence that attenuation of c-Myc expression by BMP-2
      may be involved in BMP-2-mediated increase in K(V) channel activity and
      regulation of K(V) channel expression. The increased K(V) channel activity may be
      involved in the proapoptotic and/or antiproliferative effects of BMP-2 on PASMC.

PMID- 16815890
TI  - Alveolar fluid reabsorption is increased in rats with compensated heart failure.
AB  - Alveolar fluid reabsorption (AFR) is important in keeping the air spaces free of
      edema. This process is accomplished via active transport of Na(+) across the
      alveolo-capillary barrier mostly by apical Na(+) channels and basolateral Na(+)
      K(+)-ATPases. Recently, we have reported that acute elevation of left atrial
      pressures is associated with decreased AFR in isolated rat lungs. However, the
      effect of chronic elevation of pulmonary capillary pressure, such as seen in
      patients with congestive heart failure (CHF), on AFR is unknown. CHF was induced
      by creating an aorto-caval fistula (ACF) in Sprague-Dawley male rats. Seven days
      after the placement of the fistula, AFR was studied in the isolated perfused rat
      lung model. AFR in control rats was 0.49 +/- 0.02 ml/h (all values are means +/-
      SE) and increased by approximately 40% (0.69 +/- 0.03 ml/h) in rats with chronic
      CHF (P < 0.001). The albumin flux from the pulmonary circulation into the air
      spaces did not increase in the experimental groups, indicating that lung
      permeability for large solutes was not increased. Na(+)-K(+)-ATPase activity and
      protein abundance at the plasma membrane of distal alveolar epithelial tissue
      were significantly increased in CHF rats compared with controls. These changes
      were associated with increased plasma norepinephrine levels in CHF rats compared
      with controls. We provide evidence that in a rat model of chronic compensated
      CHF, AFR is increased, possibly due to increased endogenous norepinephrine
      upregulating active sodium transport and protecting against alveolar flooding.

PMID- 16815891
TI  - Isoprostane-induced airway hyperresponsiveness is dependent on internal Ca2+
      handling and Rho/ROCK signaling.
AB  - We previously reported the ability of isoprostanes to induce airway
      hyperresponsiveness (AHR). In this study, we examined the signaling mechanisms
      underlying that phenomenon with the standard muscle bath technique. Responses to
      a threshold concentration of carbachol (CCh, 3 x 10(-9) M) were significantly
      augmented by pretreatment for 20 min with 8-isoprostaglandin E(2) (15-E(2t)-IsoP,
      10(-6) M): this AHR was obliterated in tissues pretreated with the selective Rho
      kinase (ROCK) inhibitor Y-27632 added 20 min before isoprostane, but not by
      cyclopiazonic acid (CPA). Increasing the CCh concentration to 3 x 10(-8) M (still
      considerably less than the half-maximally effective concentration of CCh) evoked
      larger contractions that were also augmented significantly by 15-E(2t)-IsoP: this
      AHR was completely abolished in tissues pretreated with CPA as well as those
      pretreated with Y-27632. We noted, however, that Y-27632 and CPA profoundly
      effect baseline tone and the cholinergic response per se, which confounds the
      interpretation of the data summarized above. We therefore modified the protocol
      by using combinations of CCh and blocker (CPA, Y-27632, or nifedipine) that were
      equieffective. In this way, we found that AHR could not be demonstrated under
      conditions in which Rho/ROCK signaling or Ca(2+) release was abolished (by Y
      27632 and CPA, respectively). Likewise, other autacoids that act through G
      protein-coupled receptors via Rho/ROCK and Ca(2+) release (serotonin, histamine)
      mimicked this effect of isoprostane, whereas bradykinin did not. We conclude that
      isoprostane-induced AHR is mediated in part through an action on Rho/ROCK
      signaling. This novel finding may contribute to a better understanding of the
      mechanisms underlying AHR and asthma.

PMID- 16815892
TI  - Dissociation between alveolar transmigration of neutrophils and lung injury in
      hyperoxia.
AB  - The objective of this study was to quantitatively assess changes in cell adhesion
      molecule (CAM) expression on the pulmonary endothelial surface during hyperoxia
      and to assess the functional significance of those changes on cellular
      trafficking and development of oxygen-induced lung injury. Mice were placed in
      >95% O(2) for 0-72 h, and pulmonary injury and neutrophil (PMN) sequestration
      were assessed. Specific pulmonary CAM expression was quantified with a dual
      radiolabeled MAb technique. To test the role of CAMs in PMN trafficking during
      hyperoxia, blocking MAbs to murine P-selectin, ICAM-1, or platelet-endothelial
      cell adhesion molecule-1 (PECAM-1) were injected in wild-type mice. Mice
      genetically deficient in these CAMs and PMN-depleted mice were also evaluated.
      PMN sequestration occurred within 8 h of hyperoxia, although alveolar emigration
      occurred later (between 48 and 72 h), coincident with rapid escalation of the
      lung injury. Hyperoxia significantly increased pulmonary uptake of radiolabeled
      antibodies to P-selectin, ICAM-1, and PECAM-1, reflecting an increase in their
      level on pulmonary endothelium and possibly sequestered blood cells. Although
      both anti-PECAM-1 and anti-ICAM-1 antibodies suppressed PMN alveolar influx in
      wild-type mice, only mice genetically deficient in PECAM-1 showed PMN influx
      suppression. Neither CAM blockade, nor genetic deficiency, nor PMN depletion
      attenuated lung injury. We conclude that early pulmonary PMN retention during
      hyperoxia is not temporally associated with an increase in endothelial CAMs;
      however, subsequent PMN emigration into the alveolar space may be supported by
      PECAM-1 and ICAM-1. Blocking PMN recruitment did not prevent lung injury,
      supporting dissociation between PMN infiltration and lung injury during hyperoxia
      in mice.

PMID- 16815893
TI  - A natural coarse graining for simulating large biomolecular motion.
AB  - Various coarse graining schemes have been proposed to speed up computer
      simulations of the motion within large biomolecules, which can contain hundreds
      of thousands of atoms. We point out here that there is a very natural way of
      doing this, using the rigid regions identified within a biomolecule as the coarse
      grain elements. Subsequently, computer resources can be concentrated on the
      flexible connections between the rigid units. Examples of the use of such
      techniques are given for the protein barnase and the maltodextrin binding
      protein, using the geometric simulation technique FRODA and the rigidity enhanced
      elastic network model RCNMA to compute mobilities and atomic displacements.

PMID- 16815894
TI  - Frequency division multiplexed multichannel high-speed fluorescence confocal
      microscope.
AB  - In this article, we report a new type of fluorescence confocal microscope:
      frequency division multiplexed multichannel fluorescence confocal microscope, in
      which we encode the spatial location information into the frequency domain. In
      this microscope, the exciting laser beam is first split into multiple beams and
      each beam is modulated at a different frequency. These multiple beams are focused
      at different locations of the target to form multiple focal points, which further
      generate multiple fluorescent emission spots. The fluorescent emissions from
      different focal points are also modulated at different frequencies, because the
      exciting beams are modulated at different frequencies (or difference carrier
      frequency). Then, all the fluorescent emissions (modulated at different
      frequencies) are collected together and detected by a highly sensitive, large
      dynamic-range photomultiplier tube. By demodulating the detected signal (i.e.,
      via the Fourier transform), we can distinguish the fluorescent light emitted from
      the different locations by the corresponding carrier frequencies. The major
      advantage of this unique fluorescence confocal microscope is that it not only has
      a high sensitivity because of the use of photomultiplier tube but also can get
      multiple-point data simultaneously, which is crucial to study the dynamic
      behavior of many biological process. As an initial step, to verify the
      feasibility of the proposed multichannel confocal microscope, we have developed a
      two-channel confocal fluorescence microscope and applied it to study the dynamic
      behavior of the changes of the calcium ion concentration during the single
      cardiac myocyte contraction. Our preliminary experimental results demonstrated
      that we could indeed realize multichannel confocal fluorescence microscopy by
      utilizing the frequency division multiplexed microscope, which could become an
      effective tool to study the dynamic behavior of many biological processes.

PMID- 16815895
TI  - Versatility and connectivity efficiency of bipartite transcription networks.
AB  - The modulation of promoter activity by DNA-binding transcription regulators forms
      a bipartite network between the regulators and genes, in which a smaller number
      of regulators control a much lager number of genes. To facilitate representation
      of gene expression data with the simplest possible network structure, we have
      characterized the ability of bipartite networks to describe data. This has led to
      the classification of two types of bipartite networks, versatile and
      nonversatile. Versatile networks can describe any data of the same rank, and are
      indistinguishable from one another. Nonversatile networks require constraints to
      be present in data they describe, which may be used to distinguish between
      different network topologies. By quantifying the ability of bipartite networks to
      represent data we were able to define connectivity efficiency, which is a measure
      of how economic the use of connections is within a network with respect to data
      representation and generation. We postulated that it may be desirable for an
      organism to maximize its gene expression range per network edge, since
      development of a regulatory connection may have some evolutionary cost. We found
      that the transcriptional regulatory networks of both Saccharomyces cerevisiae and
      Escherichia coli lie close to their respective connectivity efficiency maxima,
      suggesting that connectivity efficiency may have some evolutionary influence.

PMID- 16815896
TI  - Indole localization in lipid membranes revealed by molecular simulation.
AB  - It is commonly known that the amino acid residue tryptophan and its side-chain
      analogs, e.g., indole, are strongly attracted to the interfacial region of lipid
      bilayers. Phenylalanine and its side-chain analogs, e.g., benzene, do not
      localize in the interface but are distributed throughout the lipid bilayer. We
      use molecular dynamics to investigate the details of indole and benzene
      localization and orientation within a POPC bilayer and the factors that lead to
      their different properties. We identify three sites in the bilayer at which
      indole is localized: 1), a site in the interface near the glycerol moiety; 2), a
      weakly bound site in the interface near the choline moiety; and 3), a weakly
      bound site in the center of the bilayer's hydrocarbon core. Benzene is localized
      in the same three positions, but the most stable position is the hydrocarbon core
      followed by the site near the glycerol moiety. Transfer of indole from water to
      the hydrocarbon core shows a classic hydrophobic effect. In contrast, interfacial
      binding is strongly enthalpy driven. We use several different sets of partial
      charges to investigate the factors that contribute to indole's and benzene's
      orientational and spatial distribution. Our simulations show that a number of
      electrostatic interactions appear to contribute to localization, including
      hydrogen bonding to the lipid carbonyl groups, cation-pi interactions,
      interactions between the indole dipole and the lipid bilayer's strong interfacial
      electric field, and nonspecific electrostatic stabilization due to a mismatch in
      the variation of the nonpolar forces and local dielectric with position in the
      bilayer.

PMID- 16815897
TI  - Chromatin structure exhibits spatio-temporal heterogeneity within the cell
      nucleus.
AB  - Local chromatin compaction undergoes dynamic perturbations to regulate genetic
      processes. To address this, the direct measurement of the fluidity of chromatin
      structure is carried out in single live cells using steady-state anisotropy
      imaging and polarization modulation microscopy. Fluorescently tagged core and
      linker histones are used to probe different structural aspects of chromatin
      compaction. A graded spatial heterogeneity in compaction is observed for the
      chromatin besides the distinct positional ordering of core and linker histones.
      These spatio-temporal features are maintained by active processes and perturbed
      during death. With cell cycle, the distribution in compaction heterogeneity
      continually changes maximizing during M-G1 transition where it displays bimodal
      behavior. Such measurements of spatio-temporal chromatin fluidity could have
      broader implications in understanding chromatin remodeling within living cells.

PMID- 16815898
TI  - Funneled landscape leads to robustness of cellular networks: MAPK signal
      transduction.
AB  - We uncover the underlying potential energy landscape for a cellular network. We
      find that the potential energy landscape of the mitogen-activated protein-kinase
      signal transduction network is funneled toward the global minimum. The funneled
      landscape is quite robust against random perturbations. This naturally explains
      robustness from a physical point of view. The ratio of slope versus roughness of
      the landscape becomes a quantitative measure of robustness of the network.
      Funneled landscape is a realization of the Darwinian principle of natural
      selection at the cellular network level. It provides an optimal criterion for
      network connections and design. Our approach is general and can be applied to
      other cellular networks.

PMID- 16815899
TI  - Dynamics of HIV neutralization by a microbicide formulation layer: biophysical
      fundamentals and transport theory.
AB  - Topical microbicides are an emerging HIV/AIDS prevention modality. Microbicide
      biofunctionality requires creation of a chemical-physical barrier against HIV
      transmission. Barrier effectiveness derives from properties of the active
      compound and its delivery system, but little is known about how these properties
      translate into microbicide functionality. We developed a mathematical model
      simulating biologically relevant transport and HIV-neutralization processes
      occurring when semen-borne virus interacts with a microbicide delivery vehicle
      coating epithelium. The model enables analysis of how vehicle-related variables,
      and anti-HIV compound characteristics, affect microbicide performance. Results
      suggest HIV neutralization is achievable with postcoital coating thicknesses
      approximately 100 mum. Increased microbicide concentration and potency hasten
      viral neutralization and diminish penetration of infectious virus through the
      coating layer. Durable vehicle structures that restrict viral diffusion could
      provide significant protection. Our findings demonstrate the need to pair potent
      active ingredients with well-engineered formulation vehicles, and highlight the
      importance of the dosage form in microbicide effectiveness. Microbicide
      formulations can function not only as drug delivery vehicles, but also as
      physical barriers to viral penetration. Total viral neutralization with 100-mum
      thin coating layers supports future microbicide use against HIV transmission.
      This model can be used as a tool to analyze diverse factors that govern
      microbicide functionality.

PMID- 16815900
TI  - Dual-color time-integrated fluorescence cumulant analysis.
AB  - We introduce dual-color time-integrated fluorescence cumulant analysis (TIFCA) to
      analyze fluorescence fluctuation spectroscopy data. Dual-color TIFCA utilizes the
      bivariate cumulants of the integrated fluorescent intensity from two detection
      channels to extract the brightness in each channel, the occupation number, and
      the diffusion time of fluorophores simultaneously. Detecting the fluorescence in
      two detector channels introduces the possibility of differentiating fluorophores
      based on their fluorescence spectrum. We derive an analytical expression for the
      bivariate factorial cumulants of photon counts for arbitrary sampling times. The
      statistical accuracy of each cumulant is described by its variance, which we
      calculate by the moments-of-moments technique. A method that takes nonideal
      detector effects such as dead-time and afterpulsing into account is developed and
      experimentally verified. We perform dual-color TIFCA analysis on simple dye
      solutions and a mixture of dyes to characterize the performance and accuracy of
      our theory. We demonstrate the robustness of dual-color TIFCA by measuring
      fluorescent proteins over a wide concentration range inside cells. Finally we
      demonstrate the sensitivity of dual-color TIFCA by resolving EGFP/EYFP binary
      mixtures in living cells with a single measurement.

PMID- 16815901
TI  - Probing intra- versus interchain kinetic preferences of L-Thr acylation on
      dimeric VibF with mass spectrometry.
AB  - We present a method to probe intra- and interchain activities within dimeric
      nonribosomal peptide synthetases. Utilizing domain inactivation and analytical
      mass mutants in conjunction with rapid-quench, mass spectrometry, and a
      probabilistic kinetic model, we have elucidated the pre-steady-state intra- and
      interchain rates and the corresponding flux of the acylation of L-Thr onto VibF.
      Although the intra rate is significantly faster than the inter rate, the data are
      most consistent with an even flux of covalent substrate loading where neither
      pathway dominates. These pre-steady-state results confirm previous steady-state
      in vitro mutant complementation studies of VibF. Extension of this methodology to
      other dimeric nonribosomal peptide synthetases, and to the related fatty acid and
      polyketide synthases, will further our biophysical understanding of their acyl
      intermediate-processing pathways.

PMID- 16815902
TI  - The denaturation transition of DNA in mixed solvents.
AB  - The helix-to-coil denaturation transition in DNA has been investigated in mixed
      solvents at high concentration using ultraviolet light absorption spectroscopy
      and small-angle neutron scattering. Two solvents have been used: water and
      ethylene glycol. The "melting" transition temperature was found to be 94 degrees
      C for 4% mass fraction DNA/d-water and 38 degrees C for 4% mass fraction DNA/d
      ethylene glycol. The DNA melting transition temperature was found to vary
      linearly with the solvent fraction in the mixed solvents case. Deuterated
      solvents (d-water and d-ethylene glycol) were used to enhance the small-angle
      neutron scattering signal and 0.1M NaCl (or 0.0058 g/g mass fraction) salt
      concentration was added to screen charge interactions in all cases. DNA
      structural information was obtained by small-angle neutron scattering, including
      a correlation length characteristic of the inter-distance between the hydrogen
      containing (desoxyribose sugar-amine base) groups. This correlation length was
      found to increase from 8.5 to 12.3 A across the melting transition. Ethylene
      glycol and water mixed solvents were found to mix randomly in the solvation
      region in the helix phase, but nonideal solvent mixing was found in the melted
      coil phase. In the coil phase, solvent mixtures are more effective solvating
      agents than either of the individual solvents. Once melted, DNA coils behave like
      swollen water-soluble synthetic polymer chains.

PMID- 16815903
TI  - Prediction of the translocation kinetics of a protein from its mechanical
      properties.
AB  - Proteins are actively unfolded to pass through narrow channels in macromolecular
      complexes that catalyze protein translocation and degradation. Catalyzed
      unfolding shares many features that characterize the mechanical unfolding of
      proteins using the atomic force microscope (AFM). However, simulations of
      unfolding induced by the AFM and when a protein is translocated through a pore
      suggest that each process occurs by distinct pathways. The link, if any, between
      each type of unfolding, therefore, is not known. We show that the mechanical
      unfolding energy landscape of a protein, obtained using an atomistic molecular
      model, can be used to predict both the relative mechanical strength of proteins
      when unfolded using the AFM and when unfolded by translocation into a pore. We
      thus link the two processes and show that the import rate through a pore not only
      depends on the location of the initiation tag but also on the mechanical
      properties of the protein when averaged over all the possible geometries that are
      relevant for a given translocation initiation site.

PMID- 16815904
TI  - Measurement of FRET efficiency and ratio of donor to acceptor concentration in
      living cells.
AB  - Measurement of fluorescence resonance energy transfer (FRET) efficiency and the
      relative concentration of donor and acceptor fluorophores in living cells using
      the three-filter cube approach requires the determination of two constants: 1),
      the ratio of sensitized acceptor emission to donor fluorescence quenching (G
      factor) and 2), the ratio of donor/acceptor fluorescence intensity for equimolar
      concentrations in the absence of FRET (k factor). We have developed a method to
      determine G and k that utilizes two donor-acceptor fusion proteins with differing
      FRET efficiencies-the value of which need not be known. We validated the method
      by measuring the FRET efficiency and concentration ratio of the fluorescent
      proteins Cerulean and Venus in mammalian cells expressing a series of fusion
      proteins with varying stoichiometries. The method greatly simplifies quantitative
      FRET measurement in living cells as it does not require cell fixation, acceptor
      photobleaching, protein purification, or specialized equipment for determining
      fluorescence spectra or lifetime.

PMID- 16815905
TI  - Structure-based model of the stepping motor of PcrA helicase.
AB  - DNA helicases are ubiquitous molecular motors involved in cellular DNA
      metabolism. They move along single-stranded DNA (ssDNA) and separate duplex DNA
      into its component strands, utilizing the free energy from ATP hydrolysis. The
      PcrA helicase from Bacillus stearothermophilus translocates as a monomer
      progressively from the 3' end to the 5' end of ssDNA and is one of the smallest
      motor proteins structurally known in full atomic detail. Using high-resolution
      crystal structures of the PcrA-DNA complex, we performed nanosecond molecular
      dynamics simulations and derived potential energy profiles governing individual
      domain movement of the PcrA helicase along ssDNA. Based on these profiles, the
      millisecond translocation of the helicase along ssDNA was described through
      Langevin dynamics. The calculations support a domain stepping mechanism of PcrA
      helicase, in which, during one ATP hydrolysis cycle, the pulling together and
      pushing apart of domains 2A and 1A are synchronized with alternating mobilities
      of the individual domains in such a fashion that PcrA moves unidirectionally
      along ssDNA. By combining short timescale (nanoseconds) molecular dynamics and
      long timescale (milliseconds) stochastic-dynamics descriptions, our study
      suggests a structure-based mechanism of the ATP-powered unidirectional movement
      of PcrA helicase.

PMID- 16815906
TI  - Lipid peroxides promote large rafts: effects of excitation of probes in
      fluorescence microscopy and electrochemical reactions during vesicle formation.
AB  - Raft formation and enlargement was investigated in liposomes and supported
      bilayers prepared from sphingomyelin (SM), cholesterol, and unsaturated
      phospholipids; NBD-DPPE and rhodamine-(DOPE) were employed as fluorescent probes.
      Rafts were created by lowering temperature. Maintaining 20 mol % SM, fluorescence
      microscopy showed that, in the absence of photooxidation, large rafts did not
      form in giant unilamellar vesicles (GUVs) containing 20 or more mol %
      cholesterol. But if photooxidation was allowed to proceed, large rafts were
      readily observed. In population, cuvette experiments, small rafts formed without
      photooxidation at high cholesterol concentrations. Thus, photooxidation was the
      cause of raft enlargement during microscopy experiments. Because photooxidation
      results in peroxidation at lipid double bonds, photosensitization experiments
      were performed to explicitly produce peroxides of SM and an unsaturated
      phospholipid. GUVs of high cholesterol content containing the breakdown products
      of SM-peroxide, but not phospholipid-peroxide, resulted in large rafts after
      lowering temperature. In addition, GUV production by electroswelling can result
      in peroxides that cause large raft formation. The use of titanium electrodes
      eliminates this problem. In conclusion, lipid peroxides and their breakdown
      products are the cause of large raft formation in GUVs containing biological
      levels of cholesterol. It is critical that experiments investigating rafts in
      bilayer membranes avoid the production of peroxides.

PMID- 16815907
TI  - Glucose modulates [Ca2+]i oscillations in pancreatic islets via ionic and
      glycolytic mechanisms.
AB  - Pancreatic islets of Langerhans display complex intracellular calcium changes in
      response to glucose that include fast (seconds), slow ( approximately 5 min), and
      mixed fast/slow oscillations; the slow and mixed oscillations are likely
      responsible for the pulses of plasma insulin observed in vivo. To better
      understand the mechanisms underlying these diverse patterns, we systematically
      analyzed the effects of glucose on period, amplitude, and plateau fraction (the
      fraction of time spent in the active phase) of the various regimes of calcium
      oscillations. We found that in both fast and slow islets, increasing glucose had
      limited effects on amplitude and period, but increased plateau fraction. In some
      islets, however, glucose caused a major shift in the amplitude and period of
      oscillations, which we attribute to a conversion between ionic and glycolytic
      modes (i.e., regime change). Raising glucose increased the plateau fraction
      equally in fast, slow, and regime-changing islets. A mathematical model of the
      pancreatic islet consisting of an ionic subsystem interacting with a slower
      metabolic oscillatory subsystem can account for these complex islet calcium
      oscillations by modifying the relative contributions of oscillatory metabolism
      and oscillatory ionic mechanisms to electrical activity, with coupling occurring
      via K(ATP) channels.

PMID- 16815908
TI  - EGFP-tagged core and linker histones diffuse via distinct mechanisms within
      living cells.
AB  - The effect of chromatin organization on EGFP-tagged histone protein dynamics
      within the cell nucleus has been probed using fluorescence correlation and
      recovery measurements on single living HeLa cells. Our studies reveal that free
      fraction of core-particle histones exist as multimers within the cell nucleus
      whereas the linker histones exist in monomeric forms. The multimeric state of
      core histones is found to be invariant across mammalian and polytene chromosomes
      and this is ATP dependent. In contrast, the dynamics of the linker histones
      exhibits two distinct diffusion timescales corresponding to its transient binding
      and unbinding to chromatin governed by the tail domain residues. Under conditions
      of chromatin condensation induced by apoptosis, the free multimeric fraction of
      core histones is found to become immobile, while the monomeric linker histone
      mobility is partially reduced. In addition, we observe differences in nuclear
      colocalization of linker and core particle histones. These results are validated
      through Brownian dynamics simulation of core and linker histone mobility. Our
      findings provide a framework to understand the coupling between the state of
      chromatin assembly and histone protein dynamics that is central to accessing
      regulatory sites on the genome.

PMID- 16815909
TI  - Poroelastic bulk properties of the tectorial membrane measured with osmotic
      stress.
AB  - The equilibrium stress-strain relation and the pore radius of the isolated
      tectorial membrane (TM) of the mouse were determined. Polyethylene glycol (PEG),
      with molecular mass (MM) in the range 20-511 kDa, added to the TM bathing
      solution was used to exert an osmotic pressure. Strain on the TM induced by
      isosmotic PEG solutions of different molecular masses was approximately the same
      for MM > or = 200 kDa. However, for MM < or = 100 kDa, the TM strain was
      appreciably smaller. We infer that for the smaller molecular mass, PEG entered
      the TM and exerted a smaller effective osmotic pressure. The pore radius of the
      TM was estimated as 22 nm. The equilibrium stress-strain relation of the TM was
      measured using PEG with a molecular mass of 511 kDa. This relation was nonlinear
      and was fit with a power function. In the radial cochlear direction, the
      transverse stiffness of the TM was 20% stiffer in the inner than in the outer
      region. TM segments from the basal region had a larger transverse stiffness on
      average compared to sections from the apical-middle region. These measurements
      provide a quantitative basis for a poroelastic model of the TM.

PMID- 16815910
TI  - Isochron-based phase response analysis of circadian rhythms.
AB  - Circadian rhythms possess the ability to robustly entrain to the environmental
      cycles. This ability relies on the phase synchronization of circadian rhythm gene
      regulation to different environmental cues, of which light is the most obvious
      and important. The elucidation of the mechanism of circadian entrainment requires
      an understanding of circadian phase behavior. This article presents two phase
      analyses of oscillatory systems for infinitesimal and finite perturbations based
      on isochrons as a phase metric of a limit cycle. The phase response curve of
      circadian rhythm can be computed from the results of the analyses. The
      application to a mechanistic Drosophila circadian rhythm model gives
      experimentally testable hypotheses for the control mechanisms of circadian phase
      responses and evidence for the role of phase and period modulations in circadian
      photic entrainment.

PMID- 16815911
TI  - A kinetic model describing the processivity of myosin-V.
AB  - The precise details of how myosin-V coordinates the biochemical reactions and
      mechanical motions of its two head elements to engineer effective processive
      molecular motion along actin filaments remain unresolved. We compare a
      quantitative kinetic model of the myosin-V walk, consisting of five basic states
      augmented by two further states to allow for futile hydrolysis and detachments,
      with experimental results for run lengths, velocities, and dwell times and their
      dependence on bulk nucleotide concentrations and external loads in both
      directions. The model reveals how myosin-V can use the internal strain in the
      molecule to synchronize the motion of the head elements. Estimates for the rate
      constants in the reaction cycle and the internal strain energy are obtained by a
      computational comparison scheme involving an extensive exploration of the large
      parameter space. This scheme exploits the fact that we have obtained analytic
      results for our reaction network, e.g., for the velocity but also the run length,
      diffusion constant, and fraction of backward steps. The agreement with experiment
      is often reasonable but some open problems are highlighted, in particular the
      inability of such a general model to reproduce the reported dependence of run
      length on ADP concentration. The novel way that our approach explores parameter
      space means that any confirmed discrepancies should give new insights into the
      reaction network model.

PMID- 16815912
TI  - Lessons in stability from thermophilic proteins.
AB  - Studies that compare proteins from thermophilic and mesophilic organisms can
      provide insights into ability of thermophiles to function at their high habitat
      temperatures and may provide clues that enable us to better define the forces
      that stabilize all proteins. Most of the comparative studies have focused on
      thermal stability and show, as expected, that thermophilic proteins have higher
      Tm values than their mesophilic counterparts. Although these comparisons are
      useful, more detailed thermodynamic analyses are required to reach a more
      complete understanding of the mechanisms thermophilic protein employ to remain
      folded over a wider range of temperatures. This complete thermodynamic
      description allows one to generate a stability curve for a protein that defines
      how the conformational stability (DeltaG) varies with temperature. Here we
      compare stability curves for many pairs of homologous proteins from thermophilic
      and mesophilc organisms. Of the basic methods that can be employed to achieve
      enhanced thermostability, we find that most thermophilic proteins use the simple
      method that raises the DeltaG at all temperatures as the principal way to
      increase their Tm. We discuss and compare this thermodynamic method with the
      possible alternatives. In addition we propose ways that structural alterations
      and changes to the amino acid sequences might give rise to varied methods used to
      obtain thermostability.

PMID- 16815913
TI  - CIRSE: a solvation energy estimator compatible with flexible protein docking and
      design applications.
AB  - We present the Coordinate Internal Representation of Solvation Energy (CIRSE) for
      computing the solvation energy of protein configurations in terms of pairwise
      interactions between their atoms with analytic derivatives. Currently, CIRSE is
      trained to a Poisson/surface-area benchmark, but CIRSE is not meant to fit this
      benchmark exclusively. CIRSE predicts the overall solvation energy of protein
      structures from 331 NMR ensembles with 0.951+/-0.047 correlation and predicts
      relative solvation energy changes between members of individual ensembles with an
      accuracy of 15.8+/-9.6 kcal/mol. The energy of individual atoms in any of CIRSE's
      17 types is predicted with at least 0.98 correlation. We apply the model in
      energy minimization, rotamer optimization, protein design, and protein docking
      applications. The CIRSE model shows some propensity to accumulate errors in
      energy minimization as well as rotamer optimization, but these errors are
      consistent enough that CIRSE correctly identifies the relative solvation energies
      of designed sequences as well as putative docked complexes. We analyze the errors
      accumulated by the CIRSE model during each type of simulation and suggest means
      of improving the model to be generally useful for all-atom simulations.

PMID- 16815914
TI  - The nature of amino acid 482 of human ABCG2 affects substrate transport and ATP
      hydrolysis but not substrate binding.
AB  - Several members of the ATP-binding cassette (ABC) transporter superfamily,
      including P-glycoprotein and the half-transporter ABCG2, can confer multidrug
      resistance to cancer cells in culture by functioning as ATP-dependent efflux
      pumps. ABCG2 variants harboring a mutation at arginine 482 have been cloned from
      several drug-resistant cell lines, and these variants differ in their substrate
      transport phenotype. In this study, we changed the wild-type arginine 482 in
      human ABCG2 to each one of the 19 other standard amino acids and expressed each
      one transiently in HeLa cells. Using the 5D3 antibody that recognizes a cell
      surface epitope of ABCG2, we observed that all the mutants were expressed at the
      cell surface. However, the mutant ABCG2 proteins differed markedly in transport
      activity. All of the variants were capable of transporting one or more of the
      substrates used in this study, with the exception of the R482K mutant, which is
      completely devoid of transport ability. Six of the mutants (R482G, R482H, R482K,
      R482P, R482T, and R482Y) and the wild-type protein (R482wt) were selected for
      studies of basal and stimulated ATPase activity and photoaffinity labeling with
      the substrate analog [125I]iodoarylazidoprazosin. Whereas these seven ABCG2
      variants differed markedly in ATPase activity, all were able to specifically bind
      the substrate analog [125I]iodoarylazidoprazosin. These data suggest that residue
      482 plays an important role in substrate transport and ATP turnover, but that the
      nature of this amino acid may not be important for substrate recognition and
      binding.

PMID- 16815915
TI  - Cooperativity and the origins of rapid, single-exponential kinetics in protein
      folding.
AB  - The folding of naturally occurring, single-domain proteins is usually well
      described as a simple, single-exponential process lacking significant trapped
      states. Here we further explore the hypothesis that the smooth energy landscape
      this implies, and the rapid kinetics it engenders, arises due to the
      extraordinary thermodynamic cooperativity of protein folding. Studying Miyazawa
      Jernigan lattice polymers, we find that, even under conditions where the folding
      energy landscape is relatively optimized (designed sequences folding at their
      temperature of maximum folding rate), the folding of protein-like heteropolymers
      is accelerated when their thermodynamic cooperativity is enhanced by enhancing
      the nonadditivity of their energy potentials. At lower temperatures, where
      kinetic traps presumably play a more significant role in defining folding rates,
      we observe still greater cooperativity-induced acceleration. Consistent with
      these observations, we find that the folding kinetics of our computational models
      more closely approximates single-exponential behavior as their cooperativity
      approaches optimal levels. These observations suggest that the rapid folding of
      naturally occurring proteins is, in part, a consequence of their remarkably
      cooperative folding.

PMID- 16815916
TI  - Sequence of events in folding mechanism: beyond the Go model.
AB  - Simplified Go models, where only native contacts interact favorably, have proven
      useful to characterize some aspects of the folding of small proteins. The success
      of these models is limited by the fact that all residues interact in the same way
      so that the folding features of a protein are determined only by the geometry of
      its native conformation. We present an extended version of a Calpha-based Go
      model where different residues interact with different energies. The model is
      used to calculate the thermodynamics of three small proteins (Protein G, Src-SH3,
      and CI2) and the effect of mutations (DeltaDeltaGU-N, DeltaDeltaGdouble dagger-N,
      DeltaDeltaGdouble dagger-U, and phi-values) on the wild-type sequence. The model
      allows us to investigate some of the most controversial areas in protein folding,
      such as its earliest stages and the nature of the unfolded state, subjects that
      have lately received particular attention.

PMID- 16815917
TI  - Phylogenetic and mutational analyses reveal key residues for UDP-glucuronic acid
      binding and activity of beta1,3-glucuronosyltransferase I (GlcAT-I).
AB  - The beta1,3-glucuronosyltransferases are responsible for the completion of the
      protein-glycosaminoglycan linkage region of proteoglycans and of the HNK1 epitope
      of glycoproteins and glycolipids by transferring glucuronic acid from UDP-alpha-D
      glucuronic acid (UDP-GlcA) onto a terminal galactose residue. Here, we develop
      phylogenetic and mutational approaches to identify critical residues involved in
      UDP-GlcA binding and enzyme activity of the human beta1,3-glucuronosyltransferase
      I (GlcAT-I), which plays a key role in glycosaminoglycan biosynthesis. Phylogeny
      analysis identified 119 related beta1,3-glucuronosyltransferase sequences in
      vertebrates, invertebrates, and plants that contain eight conserved peptide
      motifs with 15 highly conserved amino acids. Sequence homology and structural
      information suggest that Y84, D113, R156, R161, and R310 residues belong to the
      UDP-GlcA binding site. The importance of these residues is assessed by site
      directed mutagenesis, UDP affinity and kinetic analyses. Our data show that
      uridine binding is primarily governed by stacking interactions with the phenyl
      group of Y84 and also involves interactions with aspartate 113. Furthermore, we
      found that R156 is critical for enzyme activity but not for UDP binding, whereas
      R310 appears less important with regard to both activity and UDP interactions.
      These results clearly discriminate the function of these two active site residues
      that were predicted to interact with the pyrophosphate group of UDP-GlcA.
      Finally, mutation of R161 severely compromises GlcAT-I activity, emphasizing the
      major contribution of this invariant residue. Altogether, this phylogenetic
      approach sustained by biochemical analyses affords new insight into the
      organization of the beta1,3-glucuronosyltransferase family and distinguishes the
      respective importance of conserved residues in UDP-GlcA binding and activity of
      GlcAT-I.

PMID- 16815918
TI  - Bacteriorhodopsin chimeras containing the third cytoplasmic loop of bovine
      rhodopsin activate transducin for GTP/GDP exchange.
AB  - The mechanisms by which G-protein-coupled receptors (GPCRs) activate G-proteins
      are not well understood due to the lack of atomic structures of GPCRs in an
      active form or in GPCR/G-protein complexes. For study of GPCR/G-protein
      interactions, we have generated a series of chimeras by replacing the third
      cytoplasmic loop of a scaffold protein bacteriorhodopsin (bR) with various
      lengths of cytoplasmic loop 3 of bovine rhodopsin (Rh), and one such chimera
      containing loop 3 of the human beta2-adrenergic receptor. The chimeras expressed
      in the archaeon Halobacterium salinarum formed purple membrane lattices thus
      facilitating robust protein purification. Retinal was correctly incorporated into
      the chimeras, as determined by spectrophotometry. A 2D crystal (lattice) was
      evidenced by circular dichroism analysis, and proper organization of homotrimers
      formed by the bR/Rh loop 3 chimera Rh3C was clearly illustrated by atomic force
      microscopy. Most interestingly, Rh3C (and Rh3G to a lesser extent) was functional
      in activation of GTPgamma35S/GDP exchange of the transducin alpha subunit
      (Galphat) at a level 3.5-fold higher than the basal exchange. This activation was
      inhibited by GDP and by a high-affinity peptide analog of the Galphat C terminus,
      indicating specificity in the exchange reaction. Furthermore, a specific physical
      interaction between the chimera Rh3C loop 3 and the Galphat C terminus was
      demonstrated by cocentrifugation of transducin with Rh3C. This Galphat-activating
      bR/Rh chimera is highly likely to be a useful tool for studying GPCR/G-protein
      interactions.

PMID- 16815919
TI  - Structural studies of human alkaline phosphatase in complex with strontium:
      implication for its secondary effect in bones.
AB  - Strontium is used in the treatment of osteoporosis as a ranelate compound, and in
      the treatment of painful scattered bone metastases as isotope. At very high doses
      and in certain conditions, it can lead to osteomalacia characterized by
      impairment of bone mineralization. The osteomalacia symptoms resemble those of
      hypophosphatasia, a rare inherited disorder associated with mutations in the gene
      encoding for tissue-nonspecific alkaline phosphatase (TNAP). Human alkaline
      phosphatases have four metal binding sites--two for zinc, one for magnesium, and
      one for calcium ion--that can be substituted by strontium. Here we present the
      crystal structure of strontium-substituted human placental alkaline phosphatase
      (PLAP), a related isozyme of TNAP, in which such replacement can have important
      physiological implications. The structure shows that strontium substitutes the
      calcium ion with concomitant modification of the metal coordination. The use of
      the flexible and polarizable force-field TCPEp (topological and classical
      polarization effects for proteins) predicts that calcium or strontium has similar
      interaction energies at the calcium-binding site of PLAP. Since calcium helps
      stabilize a large area that includes loops 210-228 and 250-297, its substitution
      by strontium could affect the stability of this region. Energy calculations
      suggest that only at high doses of strontium, comparable to those found for
      calcium, can strontium substitute for calcium. Since osteomalacia is observed
      after ingestion of high doses of strontium, alkaline phosphatase is likely to be
      one of the targets of strontium, and thus this enzyme might be involved in this
      disease.

PMID- 16815920
TI  - A limited universe of membrane protein families and folds.
AB  - One of the goals of structural genomics is to obtain a structural representative
      of almost every fold in nature. A recent estimate suggests that 70%-80% of
      soluble protein domains identified in the first 1000 genome sequences should be
      covered by about 25,000 structures-a reasonably achievable goal. As no current
      estimates exist for the number of membrane protein families, however, it is not
      possible to know whether family coverage is a realistic goal for membrane
      proteins. Here we find that virtually all polytopic helical membrane protein
      families are present in the already known sequences so we can make an estimate of
      the total number of families. We find that only approximately 700 polytopic
      membrane protein families account for 80% of structured residues and
      approximately 1700 cover 90% of structured residues. While apparently a finite
      and reachable goal, we estimate that it will likely take more than three decades
      to obtain the structures needed for 90% residue coverage, if current trends
      continue.

PMID- 16815921
TI  - Crystal structure of trehalose-6-phosphate phosphatase-related protein:
      biochemical and biological implications.
AB  - We report here the crystal structure of a trehalose-6-phosphate phosphatase
      related protein (T6PP) from Thermoplasma acidophilum, TA1209, determined by the
      dual-wavelength anomalous diffraction (DAD) method. T6PP is a member of the
      haloacid dehalogenase (HAD) superfamily with significant sequence homology with
      trehalose-6-phosphate phosphatase, phosphoserine phosphatase, P-type ATPases and
      other members of the family. T6PP possesses a core domain of known alpha/beta
      hydrolase fold, characteristic of the HAD family, and a cap domain, with a
      tertiary fold consisting of a four-stranded beta-sheet with two alpha-helices on
      one side of the sheet. An active-site magnesium ion and a glycerol molecule bound
      at the interface between the two domains provide insight into the mode of
      substrate binding by T6PP. A trehalose-6-phosphate molecule modeled into a cage
      formed by the two domains makes favorable interactions with the protein molecule.
      We have confirmed that T6PP is a trehalose phosphatase from amino acid sequence,
      three-dimensional structure, and biochemical assays.

PMID- 16815922
TI  - The layered fold of the TSR domain of P. falciparum TRAP contains a heparin
      binding site.
AB  - Thrombospondin-related anonymous protein, TRAP, has a critical role in the
      hepatocyte invasion step of Plasmodium sporozoites, the transmissible form of the
      parasite causing malaria. The extracellular domains of this sporozoite surface
      protein interact with hepatocyte surface receptors whereas its intracellular
      domain acts as a link to the sporozoite actomyosin motor system. Liver heparan
      sulfate proteoglycans have been identified as potential ligands for TRAP.
      Proteoglycan binding has been associated with the A- and TSR domains of TRAP. We
      present the solution NMR structure of the TSR domain of TRAP and a chemical shift
      mapping study of its heparin binding epitope. The domain has an elongated
      structure stabilized by an array of tryptophan and arginine residues as well as
      disulfide bonds. The fold is very similar to those of thrombospondin type-1 (TSP
      1) and F-spondin TSRs. The heparin binding site of TRAP-TSR is located in the N
      terminal half of the structure, the layered side chains forming an integral part
      of the site. The smallest heparin fragment capable of binding to TRAP-TSR is a
      tetrasaccharide.

PMID- 16815948
TI  - Proteomic analysis of the extraembryonic tissue from cloned porcine embryos.
AB  - Cloned animals developed from somatic cell nuclear transfer (SCNT) embryos are
      useful resources for agricultural and medical applications. However, the birth
      rate in the cloned animals is very low, and the cloned animals that have survived
      show various developmental defects. In this report, we present the morphology and
      differentially regulated proteins in the extraembryonic tissue from SCNT embryos
      to understand the molecular nature of the tissue. We examined 26-day-old SCNT
      porcine embryos at which the sonogram can first detect pregnancy. The
      extraembryonic tissue from SCNT embryos was abnormally small compared with the
      control. In the proteomic analysis with the SCNT extraembryonic tissue, 39
      proteins were identified as differentially regulated proteins. Among up-regulated
      proteins, Annexins and Hsp27 were found. They are closely related to the
      processes of apoptosis. Among down-regulated proteins, Peroxiredoxins and
      anaerobic glycolytic enzymes were identified. In the Western blot analysis,
      antioxidant enzymes and the antiapoptotic Bcl-2 protein were down-regulated, and
      caspases were up-regulated. In the terminal deoxynucleotidyltransferase-mediated
      dUTP nick end labeling (TUNEL) assay with the placenta from SCNT embryos,
      apoptotic trophoblasts were observed. These results demonstrate that a major
      reason for the low birth rate of cloned animals is due to abnormal apoptosis in
      the extraembryonic tissue during early pregnancy.

PMID- 16815949
TI  - A dataset of human fetal liver proteome identified by subcellular fractionation
      and multiple protein separation and identification technology.
AB  - A high throughput process including subcellular fractionation and multiple
      protein separation and identification technology allowed us to establish the
      protein expression profile of human fetal liver, which was composed of at least
      2,495 distinct proteins and 568 non-isoform groups identified from 64,960
      peptides and 24,454 distinct peptides. In addition to the basic protein
      identification mentioned above, the MS data were used for complementary
      identification and novel protein mining. By doing the analysis with integrated
      protein, expressed sequence tag, and genome datasets, 223 proteins and 15
      peptides were complementarily identified with high quality MS/MS data.

PMID- 16815950
TI  - The hpa1 mutant of Arabidopsis reveals a crucial role of histidine homeostasis in
      root meristem maintenance.
AB  - Histidine (His) is an essential ingredient for protein synthesis and is required
      by all living organisms. In higher plants, although there is considerable
      evidence that His is essential for plant growth and survival, there is very
      little information as to whether it plays any specific role in plant development.
      Here, we present evidence for such a role of this amino acid in root development
      in Arabidopsis (Arabidopsis thaliana) from the characterization of a novel
      Arabidopsis mutant, hpa1, which has a very short root system and carries a
      mutation in one of the two Arabidopsis histidinol-phosphate aminotransferase
      (HPA) genes, AtHPA1. We have established that AtHPA1 encodes a functional HPA and
      that its complete knockout is embryo lethal. Biochemical analysis shows that the
      mutation in hpa1 only resulted in a 30% reduction in free His content and had no
      significant impact on the total His content. It did not cause any known symptoms
      of His starvation. However, the mutant displayed a specific developmental defect
      in root meristem maintenance and was unable to sustain primary root growth 2 d
      after germination. We have demonstrated that the root meristem failure in the
      mutant is tightly linked to the reduction in free His content and could be
      rescued by either exogenous His supplementation or AtHPA1 overexpression. Our
      results therefore reveal an important role of His homeostasis in plant
      development.

PMID- 16815951
TI  - Efficient virus-induced gene silencing in Arabidopsis.
AB  - Virus-induced gene silencing (VIGS) is a plant RNA-silencing technique that uses
      viral vectors carrying a fragment of a gene of interest to generate double
      stranded RNA, which initiates the silencing of the target gene. Several viral
      vectors have been developed for VIGS and they have been successfully used in
      reverse genetics studies of a variety of processes occurring in plants. This
      approach has not been widely adopted for the model dicotyledonous species
      Arabidopsis (Arabidopsis thaliana), possibly because, until now, there has been
      no easy protocol for effective VIGS in this species. Here, we show that a widely
      used tobacco rattle virus-based VIGS vector can be used for silencing genes in
      Arabidopsis ecotype Columbia-0. The protocol involves agroinfiltration of VIGS
      vectors carrying fragments of genes of interest into seedlings at the two- to
      three-leaf stage and requires minimal modification of existing protocols for VIGS
      with tobacco rattle virus vectors in other species like Nicotiana benthamiana and
      tomato (Lycopersicon esculentum). The method described here gives efficient
      silencing in Arabidopsis ecotype Columbia-0. We show that VIGS can be used to
      silence genes involved in general metabolism and defense and it is also effective
      at knocking down expression of highly expressed transgenes. A marker system to
      monitor the progress and efficiency of VIGS is also described.

PMID- 16815952
TI  - Overexpression of a protein phosphatase 2C from beech seeds in Arabidopsis shows
      phenotypes related to abscisic acid responses and gibberellin biosynthesis.
AB  - A functional abscisic acid (ABA)-induced protein phosphatase type 2C (PP2C) was
      previously isolated from beech (Fagus sylvatica) seeds (FsPP2C2). Because
      transgenic work is not possible in beech, in this study we overexpressed this
      gene in Arabidopsis (Arabidopsis thaliana) to provide genetic evidence on FsPP2C2
      function in seed dormancy and other plant responses. In contrast with other PP2Cs
      described so far, constitutive expression of FsPP2C2 in Arabidopsis, under the
      cauliflower mosaic virus 35S promoter, produced enhanced sensitivity to ABA and
      abiotic stress in seeds and vegetative tissues, dwarf phenotype, and delayed
      flowering, and all these effects were reversed by gibberellic acid application.
      The levels of active gibberellins (GAs) were reduced in 35S:FsPP2C2 plants,
      although transcript levels of AtGA20ox1 and AtGA3ox1 increased, probably as a
      result of negative feedback regulation, whereas the expression of GASA1 was
      induced by GAs. Additionally, FsPP2C2-overexpressing plants showed a strong
      induction of the Responsive to ABA 18 (RAB18) gene. Interestingly, FsPP2C2
      contains two nuclear targeting sequences, and transient expression assays
      revealed that ABA directed this protein to the nucleus. Whereas other plant PP2Cs
      have been shown to act as negative regulators, our results support the hypothesis
      that FsPP2C2 is a positive regulator of ABA. Moreover, our results indicate the
      existence of potential cross-talk between ABA signaling and GA biosynthesis.

PMID- 16815953
TI  - Impaired photosynthesis in phosphatidylglycerol-deficient mutant of
      cyanobacterium Anabaena sp. PCC7120 with a disrupted gene encoding a putative
      phosphatidylglycerophosphatase.
AB  - Phosphatidylglycerol (PG) is a ubiquitous phospholipid in thylakoid membranes of
      cyanobacteria and chloroplasts and plays an important role in the structure and
      function of photosynthetic membranes. The last step of the PG biosynthesis is
      dephosphorylation of phosphatidylglycerophosphate (PGP) catalyzed by PGP
      phosphatase. However, the gene-encoding PGP phosphatase has not been identified
      and cloned from cyanobacteria or higher plants. In this study, we constructed a
      PG-deficient mutant from cyanobacterium Anabaena sp. PCC7120 with a disrupted
      gene (alr1715, a gene for Alr1715 protein, GenBank accession no. BAB78081)
      encoding a putative PGP phosphatase. The obtained mutant showed an approximately
      30% reduction in the cellular content of PG. Following the reduction in the PG
      content, the photoautotrophical growth of the mutant was restrained, and the
      cellular content of chlorophyll was decreased. The decreases in net
      photosynthetic and photosystem II (PSII) activities on a cell basis also occurred
      in this mutant. Simultaneously, the photochemical efficiency of PSII was
      considerably declined, and less excitation energy was transferred toward PSII.
      These findings demonstrate that the alr1715 gene of Anabaena sp. PCC7120 is
      involved in the biosynthesis of PG and essential for photosynthesis.

PMID- 16815954
TI  - Induction of differentiation in the shoot apical meristem by transient
      overexpression of a retinoblastoma-related protein.
AB  - The shoot apical meristem contains cells that undergo continual growth and
      division to generate the building blocks for the aerial portion of the plant. As
      cells leave the meristem, they undergo differentiation to form specific cell
      types. Most notably, heterotrophic cells of the meristem rapidly gain autotrophic
      capability by synthesis and assembly of components of the chloroplast. At the
      same time, cells undergo enlargement via vacuolation. Despite significant
      advances in the characterization of transcriptional networks involved in meristem
      maintenance and leaf determination, our understanding of the actual mechanism of
      meristem cell differentiation remains very limited. Using a microinduction
      technique, we show that local, transient overexpression of a retinoblastoma
      related (RBR) protein in the shoot apical meristem is sufficient to trigger cells
      in the meristem to undergo the initial stages of differentiation. Taken together
      with recent data showing that RBR protein plays a key role in restricting stem
      cell differentiation in the root apical meristem, our data contribute to an
      emerging picture of RBR proteins as a central part of the mechanism controlling
      meristem cell differentiation.

PMID- 16815955
TI  - Rapid, futile K+ cycling and pool-size dynamics define low-affinity potassium
      transport in barley.
AB  - Using the short-lived radiotracer 42K+, we present a comprehensive subcellular
      flux analysis of low-affinity K+ transport in plants. We overturn the paradigm of
      cytosolic K+ pool-size homeostasis and demonstrate that low-affinity K+ transport
      is characterized by futile cycling of K+ at the plasma membrane. Using two
      methods of compartmental analysis in intact seedlings of barley (Hordeum vulgare
      L. cv Klondike), we present data for steady-state unidirectional influx, efflux,
      net flux, cytosolic pool size, and exchange kinetics, and show that, with
      increasing external [K+] ([K+]ext), both influx and efflux increase dramatically,
      and that the ratio of efflux to influx exceeds 70% at [K+]ext > or = 20 mm.
      Increasing [K+]ext, furthermore, leads to a shortening of the half-time for
      cytosolic K+ exchange, to values 2 to 3 times lower than are characteristic of
      high-affinity transport. Cytosolic K+ concentrations are shown to vary between 40
      and 200 mm, depending on [K+]ext, on nitrogen treatment (NO3- or NH4+), and on
      the dominant mode of transport (high- or low-affinity transport), illustrating
      the dynamic nature of the cytosolic K+ pool, rather than its homeostatic
      maintenance. Based on measurements of trans-plasma membrane electrical potential,
      estimates of cytosolic K+ pool size, and the magnitude of unidirectional K+
      fluxes, we describe efflux as the most energetically demanding of the cellular K+
      fluxes that constitute low-affinity transport.

PMID- 16815956
TI  - Mutations in Arabidopsis yellow stripe-like1 and yellow stripe-like3 reveal their
      roles in metal ion homeostasis and loading of metal ions in seeds.
AB  - Here, we describe two members of the Arabidopsis (Arabidopsis thaliana) Yellow
      Stripe-Like (YSL) family, AtYSL1 and AtYSL3. The YSL1 and YSL3 proteins are
      members of the oligopeptide transporter family and are predicted to be integral
      membrane proteins. YSL1 and YSL3 are similar to the maize (Zea mays) YS1
      phytosiderophore transporter (ZmYS1) and the AtYSL2 iron (Fe)-nicotianamine
      transporter, and are predicted to transport metal-nicotianamine complexes into
      cells. YSL1 and YSL3 mRNAs are expressed in both root and shoot tissues, and both
      are regulated in response to the Fe status of the plant. Beta-glucuronidase
      reporter expression, driven by YSL1 and YSL3 promoters, reveals expression
      patterns of the genes in roots, leaves, and flowers. Expression was highest in
      senescing rosette leaves and cauline leaves. Whereas the single mutants ysl1 and
      ysl3 had no visible phenotypes, the ysl1ysl3 double mutant exhibited Fe
      deficiency symptoms, such as interveinal chlorosis. Leaf Fe concentrations are
      decreased in the double mutant, whereas manganese, zinc, and especially copper
      concentrations are elevated. In seeds of double-mutant plants, the concentrations
      of Fe, zinc, and copper are low. Mobilization of metals from leaves during
      senescence is impaired in the double mutant. In addition, the double mutant has
      reduced fertility due to defective anther and embryo development. The proposed
      physiological roles for YSL1 and YSL3 are in delivery of metal micronutrients to
      and from vascular tissues.

PMID- 16815957
TI  - Expression and functional analyses of the plastid lipid-associated protein CHRC
      suggest its role in chromoplastogenesis and stress.
AB  - Chromoplastogenesis during flower development and fruit ripening involves the
      dramatic overaccumulation of carotenoids sequestered into structures containing
      lipids and proteins called plastid lipid-associated proteins (PAPs). CHRC, a
      cucumber (Cucumis sativus) PAP, has been suggested to be transcriptionally
      activated in carotenoid-accumulating flowers by gibberellin (GA). Mybys, a MYB
      like trans-activator identified here, may represent a chromoplastogenesis-related
      factor: Its expression is flower specific and parallels that of ChrC during
      flower development; moreover, as revealed by stable ectopic and transient
      expression assays, it specifically trans-activates ChrC promoter in flowers
      accumulating carotenoids and flavonoids. A detailed dissection of ChrC promoter
      revealed a GA-responsive element, gacCTCcaa, the mutation of which abolished ChrC
      activation by GA. This cis-element is different from the GARE motif and is
      involved in ChrC activation probably via negative regulation, similar to other GA
      responsive systems. The GA responsiveness and MYBYS floral activation of the ChrC
      promoter do not overlap with respect to cis-elements. To study the functionality
      of CHRC, which is activated in vegetative tissues similar to other PAPs by
      various biotic and abiotic stresses, we employed a tomato (Lycopersicon
      esculentum) plant system and generated RNAi-transgenic lines with suppressed
      LeCHRC. Transgenic flowers accumulated approximately 30% less carotenoids per
      unit protein than controls, indicating an interrelationship between PAPs and
      flower-specific carotenoid accumulation in chromoplasts. Moreover, the transgenic
      LeCHRC-suppressed plants were significantly more susceptible to Botrytis cinerea
      infection, suggesting CHRC's involvement in plant protection under stress
      conditions and supporting the general, evolutionarily preserved role of PAPs.

PMID- 16815958
TI  - Cold-active winter rye glucanases with ice-binding capacity.
AB  - Extracellular pathogenesis-related proteins, including glucanases, are expressed
      at cold temperatures in winter rye (Secale cereale) and display antifreeze
      activity. We have characterized recombinant cold-induced glucanases from winter
      rye to further examine their roles and contributions to cold tolerance. Both
      basic beta-1,3-glucanases and an acidic beta-1,3;1,4-glucanase were expressed in
      Escherichia coli, purified, and assayed for their hydrolytic and antifreeze
      activities in vitro. All were found to be cold active and to retain partial
      hydrolytic activity at subzero temperatures (e.g. 14%-35% at -4 degrees C). The
      two types of glucanases had antifreeze activity as measured by their ability to
      modify the growth of ice crystals. Structural models for the winter rye beta-1,3
      glucanases were developed on which putative ice-binding surfaces (IBSs) were
      identified. Residues on the putative IBSs were charge conserved for each of the
      expressed glucanases, with the exception of one beta-1,3-glucanase recovered from
      nonacclimated winter rye in which a charged amino acid was present on the
      putative IBS. This protein also had a reduced antifreeze activity relative to the
      other expressed glucanases. These results support the hypothesis that winter rye
      glucanases have evolved to inhibit the formation of large, potentially fatal ice
      crystals, in addition to having enzymatic activity with a potential role in
      resisting infection by psychrophilic pathogens. Glucanases of winter rye provide
      an interesting example of protein evolution and adaptation aimed to combat cold
      and freezing conditions.

PMID- 16815959
TI  - CYP2A13 in human respiratory tissues and lung cancers: an immunohistochemical
      study with a new peptide-specific antibody.
AB  - Human cytochrome P450 2A13 (CYP2A13) is highly efficient in the metabolic
      activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK), and another potent carcinogen, aflatoxin B1 (AFB1). Although
      previous studies demonstrated that CYP2A13 mRNA is predominantly expressed in
      human respiratory tissues, expression of CYP2A13 protein in these tissues and the
      involved cell types have not been determined because of the lack of CYP2A13
      specific antibodies. To explore the toxicological and physiological function of
      CYP2A13, it is important to understand the tissue/cellular distribution of
      CYP2A13 protein. In this study, we generated a peptide-specific antibody against
      human CYP2A13 and demonstrated by immunoblot analysis that this antibody does not
      cross-react with heterologously expressed human CYP2A6 and mouse CYP2A5 proteins,
      both sharing a high degree of amino acid sequence similarity with CYP2A13. Nor
      does the antibody cross-react with heterologously expressed human CYP3A4, CYP2S1,
      or any of the cytochrome P450 enzymes present in the human liver microsomes.
      Using this highly specific antibody for immunohistochemical staining, we detected
      a high level of CYP2A13 protein expression in the epithelial cells of human
      bronchus and trachea, but a rare distribution in the alveolar cells. There was
      little expression of CYP2A13 protein in different types of lung cancers. In
      consideration of the high efficiency of CYP2A13 in NNK metabolic activation, our
      result is consistent with the reported observations that most smoking-related
      human lung cancers are bronchogenic and supports that CYP2A13-catalyzed in situ
      activation may play a critical role in human lung carcinogenesis related to NNK
      and AFB1 exposure.

PMID- 16815960
TI  - In vivo and in vitro metabolism of arylamine procarcinogens in acetyltransferase
      deficient mice.
AB  - Arylamine N-acetyltransferases (NATs) catalyze the biotransformation of a number
      of aromatic and heterocyclic amines, many of which are procarcinogenic agents.
      Interestingly, these enzymes are binary in nature, participating in both
      detoxification and activation reactions, and thus it is unclear what role NATs
      actually play in either preventing or enhancing toxic responses. The ultimate
      direction may be substrate-specific and dependent on its tissue-specific
      metabolism by competing, but genetically variable, drug-metabolizing enzymes. To
      investigate the effect of N-acetylation on the metabolism of some classical
      procarcinogenic arylamines, we have used our double knockout Nat1/2(-/-) mouse
      model to test both in vitro activity and the in vivo clearance of some of these
      agents. As expected, N-acetylation activity was undetectable in tissue cytosol
      preparations from Nat1/2(-/-) mice for 4-aminobiphenyl (ABP) and 2-aminofluorene
      (AF), whereas significant levels were measured in all wild-type tissue cytosols
      tested, indicating the widespread metabolism of these agents. Nat1/2(-/-) mice
      displayed a variable response with respect to in vivo pharmacokinetics. AF
      appeared to be most severely compromised, with a 3- to 4-fold increased area
      under the curve (AUC), whereas the clearance of ABP was found to be less
      dependent on N-acetylation, with no difference in ABP-AUC between wild-type and
      knockout animals. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine was neither N
      acetylated nor was its clearance affected by NAT genotype, signifying a
      dependence on other drug-metabolizing enzymes. The elucidation of the role that N
      acetylation plays in the clearance of procarcinogenic agents is the first step in
      attempting to correlate metabolism by NATs to toxic outcome prevention or
      augmentation.

PMID- 16815961
TI  - Amiodarone analog-dependent effects on CYP2C9-mediated metabolism and kinetic
      profiles.
AB  - CYP2C9 substrates can exhibit both hyperbolic and atypical kinetic profiles, and
      their metabolism can be activated or inhibited depending on the effector studied.
      CYP2C9 genetic variants can also affect both substrate turnover and kinetic
      profile. The present study assessed whether analogs of the effector amiodarone
      differentially altered the atypical kinetic profile of the substrate naproxen and
      whether this effect was genotype-dependent. Amiodarone, desethylamiodarone,
      benzbromarone, and its dimethyl analog (benz(meth)arone) were incubated with
      naproxen and either CYP2C9.1 or CYP2C9.3. Amiodarone activated naproxen
      demethylation at lower concentrations, regardless of the CYP2C9 allele, and
      inhibited metabolism at higher concentrations without altering the kinetic
      profile. Desethylamiodarone was a potent inhibitor of naproxen demethylation,
      irrespective of the CYP2C9 allele. Benzbromarone altered naproxen demethylation
      kinetics from a biphasic profile to that of a hyperbolic form in CYP2C9.1 and
      CYP2C9.3, resulting in inhibition and activation, respectively. In contrast,
      benz(meth)arone activated naproxen demethylation in both CYP2C9.1 and CYP2C9.3.
      In addition, the kinetic profile of naproxen demethylation became more hyperbolic
      at lower concentrations of benz(meth)arone and then reverted back to biphasic as
      the benz(meth)arone was increased further. Equilibrium binding and multiple
      ligand docking studies were used to propose how such similar compounds exerted
      very different effects on naproxen metabolism. In summary, effectors of CYP2C9
      metabolism can alter not only the degree of substrate turnover (activation or
      inhibition) but also the kinetic profile of metabolism of CYP2C9 substrates
      through effects on substrate binding and orientation. In addition, these kinetics
      effects are concentration- and genotype-dependent.

PMID- 16815962
TI  - Dietary inulin alleviates hepatic steatosis and xenobiotics-induced liver injury
      in rats fed a high-fat and high-sucrose diet: association with the suppression of
      hepatic cytochrome P450 and hepatocyte nuclear factor 4alpha expression.
AB  - Inulin enzymatically synthesized from sucrose is a dietary component that
      completely escapes glucide digestion. Supplementing inulin to a high-fat and high
      sucrose diet (HF) ameliorated hypertriglycemia and hepatic steatosis in 8-week
      fed rats by suppressing elevated levels of serum triacylglycerols, fatty acids,
      and glucose, and the accumulation of hepatic triacylglycerols and fatty acids.
      Inulin intake prevented phenobarbital (PB)- and dexamethasone-induced liver
      injuries in the HF group. No significant alteration in the baseline expression of
      CYP2B, CYP2C11, CYP3A, and NADPH-cytochrome P450 (P450) reductase mRNAs and
      proteins was found. In contrast, baseline and PB-treated expressions of CYP2E1
      mRNA were reduced in HF-fed rats. The induction of P450s in response to PB was
      affected by the nutritional status of the rats; mRNA levels of CYP2B1 and CYP3A1
      after PB treatment, as assessed by quantitative real-time polymerase chain
      reaction analysis were reduced in the inulin-supplemented HF (HF+I) group,
      compared with those in the HF group. Western blot analysis detected the
      corresponding changes of CYP2B and CYP3A proteins. These alterations were
      correlated with changes in hepatic thiobarbituric acid-reactive substances.
      Furthermore, no significant difference in the expression of nuclear receptors
      constitutive androstane receptor, pregnane X receptor, and retinoid X receptor
      alpha and coactivator peroxisome proliferator-activated receptor-gamma
      coactivator 1alpha proteins was found in the hepatic nucleus between the HF and
      HF+I groups, but the expression of hepatocyte nuclear factor alpha (HNF4alpha)
      protein was significantly reduced in the HF+I group. Taken together, these
      results indicate that inulin intake ameliorates PB-induced liver injury,
      associated with a decline in lipid accumulation and PB-induced expression of
      CYP2B and CYP3A, which may be related by a reduction in the nuclear expression of
      HNF4alpha.

PMID- 16815963
TI  - In vivo metabolism and final disposition of a novel nonsteroidal androgen in rats
      and dogs.
AB  - Compound S-4 (S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3
      trifluoromethyl-phenyl)-propionamide) is a novel nonsteroidal androgen agonist
      that mimics many of the beneficial pharmacologic effects of testosterone with
      lesser effects on the prostate. S-4 demonstrated high androgen receptor binding
      affinity as well as anabolic specificity during in vivo pharmacologic studies in
      rats, identifying it as the first member of a new class of selective androgen
      receptor modulators. The purpose of these studies was to determine the
      pharmacokinetics and metabolism of S-4 in dogs. S-4 showed linear
      pharmacokinetics after both intravenous (i.v.) and oral (p.o.) administrations at
      pharmacologically relevant doses, with a mean clearance of 4.6 ml/min/kg and a
      mean half-life of about 200 min. It is interesting that dose-dependent oral
      bioavailability was seen. However, at pharmacologically relevant doses, the oral
      bioavailability of S-4 was 91%. Species differences were observed in S-4
      metabolism; the major metabolic pathway for S-4 in dogs was deacetylation of the
      B-ring acetamide group and reduction of the A-ring nitro group, whereas the major
      metabolic pathway for S-4 in rats was hydrolysis on the amide bond and reduction
      of the A-ring nitro group. In addition, oxidative metabolites and phase II
      metabolites were identified in both rats and dogs. These studies demonstrate that
      S-4 maintains its promising pharmacokinetic properties in dogs (i.e., high oral
      bioavailability and linear kinetics) and is largely eliminated via hepatic
      metabolism by both phase I and phase II enzymes.

PMID- 16815964
TI  - Characterization of the rhesus monkey CYP3A64 enzyme: species comparisons of
      CYP3A substrate specificity and kinetics using baculovirus-expressed recombinant
      enzymes.
AB  - The rhesus monkey (Macaca mulatta) is a primate species used extensively as a
      preclinical safety species in drug development. In this report, we describe the
      cloning, expression, and characterization of CYP3A64 (AY334551), a CYP3A4 homolog
      expressed in rhesus liver. The deduced amino acid sequence was found to be 93%
      similar to human CYP3A4, 83% similar to human CYP3A5, and identical to the
      previously reported cynomolgus monkey CYP3A8 (Komori et al., 1992). The substrate
      specificity of CYP3A64 for testosterone (0-250 microM), midazolam (0-200 microM),
      nifedipine (0-200 microM), and 7-benzoxy-4-trifluoromethylcoumarin (0-200 microM)
      were compared with recombinant enzymes from rat (CYP3A1, CYP3A2), dog (CYP3A12,
      CYP3A26), rabbit (CYP3A6), and human (CYP3A4, CYP3A5). Immunoinhibition and
      chemical inhibition of CYP3A64 was demonstrated using the inhibitory monoclonal
      antibody (MAb) 10-1-1 (anti-3A4) and ketoconazole (0-10 microM). The utility of
      CYP3A64 to be used as a standard in monkey induction assays was shown and the
      concentration of CYP3A64 protein in rhesus liver microsomes was estimated to be
      72 pmol/mg protein. In summary, these results support the utilization of rhesus
      monkey CYP3A64 for in vitro drug metabolism studies and provide a more complete
      understanding of CYP3A substrate specificities and species differences in
      metabolic capabilities.

PMID- 16815965
TI  - Detection and characterization of metabolites in biological matrices using mass
      defect filtering of liquid chromatography/high resolution mass spectrometry data.
AB  - An improved mass defect filter (MDF) method employing both drug and core
      structure filter templates was applied to the processing of high resolution
      liquid chromatography/mass spectrometry (LC/MS) data for the detection and
      structural characterization of oxidative metabolites with mass defects similar to
      or significantly different from those of the parent drugs. The effectiveness of
      this approach was investigated using nefazodone as a model compound, which is
      known to undergo multiple common and uncommon oxidative reactions. Through the
      selective removal of all ions that fall outside of the preset filter windows, the
      MDF process facilitated the detection of all 14 nefazodone metabolites presented
      in human liver microsomes in the MDF-filtered chromatograms. The capability of
      the MDF approach to remove endogenous interferences from more complex biological
      matrices was examined by analyzing omeprazole metabolites in human plasma. The
      unprocessed mass chromatogram showed no distinct indication of metabolite peaks;
      however, after MDF processing, the metabolite peaks were easily identified in the
      chromatogram. Compared with precursor ion scan and neutral loss scan techniques,
      the MDF approach was shown to be more effective for the detection of metabolites
      in a complex matrix. The comprehensive metabolite detection capability of the MDF
      approach, together with accurate mass determination, makes high resolution LC/MS
      a useful tool for the screening and identification of both common and uncommon
      drug metabolites.

PMID- 16815966
TI  - Arithmetic processing in the brain shaped by cultures.
AB  - The universal use of Arabic numbers in mathematics raises a question whether
      these digits are processed the same way in people speaking various languages,
      such as Chinese and English, which reflect differences in Eastern and Western
      cultures. Using functional MRI, we demonstrated a differential cortical
      representation of numbers between native Chinese and English speakers.
      Contrasting to native English speakers, who largely employ a language process
      that relies on the left perisylvian cortices for mental calculation such as a
      simple addition task, native Chinese speakers, instead, engage a visuo-premotor
      association network for the same task. Whereas in both groups the inferior
      parietal cortex was activated by a task for numerical quantity comparison,
      functional MRI connectivity analyses revealed a functional distinction between
      Chinese and English groups among the brain networks involved in the task. Our
      results further indicate that the different biological encoding of numbers may be
      shaped by visual reading experience during language acquisition and other
      cultural factors such as mathematics learning strategies and education systems,
      which cannot be explained completely by the differences in languages per se.

PMID- 16815967
TI  - Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon
      cancer.
AB  - Chromosomal instability (CIN), a hallmark of most colon tumors, may promote tumor
      progression by increasing the rate of genetic aberrations. CIN is thought to
      arise as a consequence of improper mitosis and spindle checkpoint activity, but
      its molecular basis remains largely elusive. The majority of colon tumors develop
      because of mutations in the tumor suppressor APC that lead to Wnt/beta-catenin
      signaling activation and subsequent transcription of target genes, including
      conductin/AXIN2. Here we demonstrate that Wnt/beta-catenin signaling causes CIN
      via up-regulation of conductin. Human colon tumor samples with CIN show
      significantly higher expression of conductin than those without. Conductin is up
      regulated during mitosis, localizes along the mitotic spindles of colon cancer
      cells, and binds to polo-like kinase 1. Ectopic expression of conductin or its up
      regulation through small interfering RNA-mediated knock-down of APC leads to CIN
      in chromosomally stable colon cancer cells. High conductin expression compromises
      the spindle checkpoint, and this requires localized polo-like kinase 1 activity.
      Knock-down of conductin by small interfering RNA in colon carcinoma cells or gene
      ablation in mouse embryo fibroblasts enforces the checkpoint.

PMID- 16815968
TI  - Pancreatic beta cells lack a low glucose and O2-inducible mitochondrial protein
      that augments cell survival.
AB  - beta cell failure is a common denominator of diabetes. Susceptibility to stress
      induced apoptosis may underlie beta cell failure and/or hamper islet
      transplantation therapy. The causal basis is not well understood. In efforts to
      identify important differences in gene expression in alpha vs. beta cells, a gene
      termed HIMP1 (Hypoglycemia/hypoxia Inducible Mitochondrial Protein, or HIG1) has
      been cloned from an alpha cell cDNA library. It is a member of a well conserved
      eukaryote protein family. In mice, its two alternatively spliced products each
      form a transmembrane loop, having an N(outside)-C(outside) orientation and are
      expressed highly in the mitochondrial inner membrane in several tissues including
      heart and pancreatic alpha cells, but not in beta cells. Ectopic expression of
      HIMP1 in MIN6 beta cells protects the cells from apoptosis induced by several
      stimuli and prolongs their survival. These results suggest an important role for
      HIMP1 in stress protective programs in mitochondria.

PMID- 16815969
TI  - O brother, where art thou? The fraternal birth-order effect on male sexual
      orientation.

PMID- 16815970
TI  - Abrupt tropical climate change: past and present.
AB  - Three lines of evidence for abrupt tropical climate change, both past and
      present, are presented. First, annually and decadally averaged delta(18)O and net
      mass-balance histories for the last 400 and 2,000 yr, respectively, demonstrate
      that the current warming at high elevations in the mid- to low latitudes is
      unprecedented for at least the last 2 millennia. Second, the continuing retreat
      of most mid- to low-latitude glaciers, many having persisted for thousands of
      years, signals a recent and abrupt change in the Earth's climate system. Finally,
      rooted, soft-bodied wetland plants, now exposed along the margins as the
      Quelccaya ice cap (Peru) retreats, have been radiocarbon dated and, when coupled
      with other widespread proxy evidence, provide strong evidence for an abrupt mid
      Holocene climate event that marked the transition from early Holocene (pre-5,000
      yr-B.P.) conditions to cooler, late Holocene (post-5,000-yr-B.P.) conditions.
      This abrupt event, approximately 5,200 yr ago, was widespread and spatially
      coherent through much of the tropics and was coincident with structural changes
      in several civilizations. These three lines of evidence argue that the present
      warming and associated glacier retreat are unprecedented in some areas for at
      least 5,200 yr. The ongoing global-scale, rapid retreat of mountain glaciers is
      not only contributing to global sea-level rise but also threatening freshwater
      supplies in many of the world's most populous regions.

PMID- 16815971
TI  - A sensor for intracellular ionic strength.
AB  - Cystathionine-beta-synthase (CBS) domains are found in >4,000 proteins in species
      from all kingdoms of life, yet their functions are largely unknown. Tandem CBS
      domains are associated with membrane transport proteins, most notably members of
      the ATP-binding cassette (ABC) superfamily; voltage-gated chloride channels and
      transporters; cation efflux systems; and various enzymes, transcription factors,
      and proteins of unknown function. We now show that tandem CBS domains in the
      osmoregulatory ABC transporter OpuA are sensors for ionic strength that control
      the transport activity through an electrostatic switching mechanism. The on/off
      state of the transporter is determined by the surface charge of the membrane and
      the internal ionic strength that is sensed by the CBS domains. By modifying the
      CBS domains, we can control the ionic strength dependence of the transporter:
      deleting a stretch of C-terminal anionic residues shifts the ionic strength
      dependence to higher values, whereas deleting the CBS domains makes the system
      largely independent of ionic strength. We present a model for the gating of
      membrane transport by ionic strength and propose a new role for CBS domains.

PMID- 16815972
TI  - Discrete steps in sensing of beta-lactam antibiotics by the BlaR1 protein of the
      methicillin-resistant Staphylococcus aureus bacterium.
AB  - Chemical sensing by cell-surface receptors to effect signal transduction is a
      ubiquitous biological event. Despite extensive structural biochemical study,
      detailed knowledge of how signal transduction occurs is largely lacking. We
      report herein a kinetic and structural study, obtained by stopped-flow IR
      spectroscopy, of the activation of the BlaR1 receptor of the Staphylococcus
      aureus bacterium by beta-lactam antibiotics. The cell-surface BlaR1 receptor
      alerts the bacterium to the presence of beta-lactam antibiotics, resulting in
      expression of the gene for a beta-lactamase enzyme. This enzyme hydrolytically
      destroys the remaining beta-lactam antibiotics. IR spectroscopic interrogation of
      the beta-lactam-BlaR1 receptor reaction has allowed the simultaneous measurement
      of the chemical events of receptor recognition of the beta-lactam and the
      characterization of the conformational changes in the BlaR1 receptor that result.
      The key chemical events in beta-lactam recognition are serine acylation and
      subsequent irreversible decarboxylation of the BlaR1 active site lysine
      carbamate. Both events are observed by stopped-flow IR kinetics and (13)C isotope
      edited IR spectroscopy. The secondary structural changes in the BlaR1 receptor
      conformation that occur as a consequence of this acylation/decarboxylation are
      predicted to correlate to the signal transduction event accomplished by this
      receptor.

PMID- 16815973
TI  - Naive CD4 T cells constitutively express CD40L and augment autoreactive B cell
      survival.
AB  - Chronic engagement of the B cell receptor by soluble autoantigen leads to reduced
      B cell survival. Using the Ig and hen egg lysozyme double transgenic mouse model,
      we demonstrate that the survival of soluble autoantigen-engaged B cells is
      further reduced in mice lacking CD4 T cells or deficient in CD40. Mixed bone
      marrow chimera experiments reveal that, under homeostatic conditions, the CD40L
      CD40 pathway can augment autoreactive B cell survival in a non-cell-autonomous
      manner. Naive CD4 T cells are shown to constitutively express CD40L mRNA and
      protein, although cell surface CD40L abundance is low because of engagement with
      CD40 on other cells. These observations indicate that the CD40L-CD40 pathway can
      augment the survival of autoantigen-engaged B cells in the absence of T cell
      activation. We propose that constitutive CD40L expression by naive CD4 T cells
      influences the composition of the B cell repertoire and may also affect the
      homeostasis of other cell types such as regulatory T cells in lymphoid organs.

PMID- 16815974
TI  - Cryptic sex and many-to-one coevolution in the fungus-growing ant symbiosis.
AB  - The fungus-growing ants have long provided a spectacular example of
      coevolutionary integration. Their ecological success is thought to depend largely
      on the evolutionary alignment of reproductive interests between ants and fungi
      after vertical transmission and the ancient suppression of fungal sexuality. In
      the present study we test these assumptions and provide the first evidence of
      recombination in attine cultivars, contradicting widely held perceptions of
      obligate clonality. In addition, we document long-distance horizontal
      transmission of symbionts between leaf-cutter ant species on mainland Central
      America and South America and those endemic to Cuba, suggesting both lack of
      pairwise coevolutionary specificity in ant/cultivar interactions and dispersal of
      symbionts independent of their ant hosts. The coevolution between leaf-cutters
      and their fungal symbionts is thus not reciprocally pairwise. Rather, a single
      widespread and sexual fungal symbiont species is engaged in multiple interactions
      with divergent ant lineages. Strict fungal clonality and vertical transmission
      evidently have not played a critical role in the long-term evolutionary or
      ecological success of this well known mutualism.

PMID- 16815975
TI  - HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN
      induced ISGylation of protein targets.
AB  - Type I IFNs induce the expression of IFN-stimulated gene 15 (ISG15) and its
      conjugation to cellular targets. ISGylation is a multistep process involving IFN
      inducible Ube1L, UbcH8, and a yet-to-be identified E3 ligase. Here we report the
      identification of an IFN-induced HECT-type E3 protein ligase, HERC5/Ceb1, which
      mediates ISGylation. We also defined a number of proteins modified by ISG15 after
      IFN triggering or HERC5 overexpression. A reduction in endogenous HERC5 by small
      interfering RNA inhibition blocks the IFN-induced ISG15 conjugation. Conversely,
      HERC5 coexpression with Ube1L and UbcH8 induces the ISG15 conjugation in vivo
      independent of IFN stimulation. A targeted substitution of Cys-994 to Ala in the
      HECT domain of HERC5 completely abrogates its E3 protein ligase activity.
      Therefore, this study demonstrates that HERC5/Ceb1 is involved in the conjugation
      of ISG15 to cellular proteins.

PMID- 16815976
TI  - CTCF binding at the H19 imprinting control region mediates maternally inherited
      higher-order chromatin conformation to restrict enhancer access to Igf2.
AB  - It is thought that the H19 imprinting control region (ICR) directs the silencing
      of the maternally inherited Igf2 allele through a CTCF-dependent chromatin
      insulator. The ICR has been shown to interact physically with a silencer region
      in Igf2, differentially methylated region (DMR)1, but the role of CTCF in this
      chromatin loop and whether it restricts the physical access of distal enhancers
      to Igf2 is not known. We performed systematic chromosome conformation capture
      analyses in the Igf2/H19 region over >160 kb, identifying sequences that interact
      physically with the distal enhancers and the ICR. We found that, on the paternal
      chromosome, enhancers interact with the Igf2 promoters but that, on the maternal
      allele, this is prevented by CTCF binding within the H19 ICR. CTCF binding in the
      maternal ICR regulates its interaction with matrix attachment region (MAR)3 and
      DMR1 at Igf2, thus forming a tight loop around the maternal Igf2 locus, which may
      contribute to its silencing. Mutation of CTCF binding sites in the H19 ICR leads
      to loss of CTCF binding and de novo methylation of a CTCF target site within Igf2
      DMR1, showing that CTCF can coordinate regional epigenetic marks. This systematic
      chromosome conformation capture analysis of an imprinting cluster reveals that
      CTCF has a critical role in the epigenetic regulation of higher-order chromatin
      structure and gene silencing over considerable distances in the genome.

PMID- 16815977
TI  - Interaction of two hereditary spastic paraplegia gene products, spastin and
      atlastin, suggests a common pathway for axonal maintenance.
AB  - Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder that is
      characterized by retrograde axonal degeneration that primarily affects long
      spinal neurons. The disease is clinically heterogeneous, and there are >20
      genetic loci identified. Here, we show a physical interaction between spastin and
      atlastin, two autosomal dominant HSP gene products. Spastin encodes a microtubule
      (MT)-severing AAA ATPase (ATPase associated with various activities), and
      atlastin encodes a Golgi-localized integral membrane protein GTPase. Atlastin
      does not regulate the enzymatic activity of spastin. We also identified a
      clinical mutation in atlastin outside of the GTPase domain that prevents
      interaction with spastin in cells. Therefore, we hypothesize that failure of
      appropriate interaction between these two HSP gene products may be
      pathogenetically relevant. These data indicate that at least a subset of HSP
      genes may define a cellular biological pathway that is important in axonal
      maintenance.

PMID- 16815978
TI  - ATP and norepinephrine contributions to sympathetic vasoconstriction of tail
      artery are altered in streptozotocin-diabetic rats.
AB  - Sympathetic vasoconstriction is susceptible to diabetes, but contributions made
      by purinergic neurotransmission in this state have not been investigated. We
      aimed to evaluate sympathetic vasoconstriction contributions by ATP and
      norepinephrine in the tail artery from streptozotocin-diabetic rats by using
      isometric vascular rings. Tail arteries were isolated from rats made diabetic 3
      mo earlier with streptozotocin (diabetic group), age-matched nondiabetic rats
      (nondiabetic injected), age-matched untreated animals (noninjected normal), and
      age-matched untreated animals in high glucose control Krebs solution (high
      glucose control). Responses to KCl (60 mM) or nerve stimulus trains of 1-100
      impulses were identical in all groups. Electrical stimulation produced
      progressively greater contractions with increasing impulse numbers. These were
      partially reduced by suramin (100 microM, P2 antagonist), NF-279 (1 microM, P2X
      blocker), and phentolamine (2 microM, alpha-blocker). For purinergic antagonists,
      blockade was greater in diabetic vessels compared with that in others. No
      differential effect could be detected for phentolamine between groups. Bath
      applied ATP (1 nM-1 mM) and norepinephrine (0.1 nM-100 microM) showed increased
      potency with diabetic group vessels. Desipramine (1 microM, norepinephrine
      reuptake inhibitor) potentiated neurally evoked responses in all groups equally
      and increased sensitivity to exogenous norepinephrine in a similar fashion.
      Histochemical labeling of sympathetic nerves with neuronal marker protein PGP-9.5
      and a sympathetic nerve-specific antibody for tyrosine hydroxylase showed no
      reduction in diabetic innervation density. We demonstrate, for the first time,
      changes in contributions of ATP and norepinephrine in sympathetic responses of
      rat tail artery in diabetes, which cannot be accounted for by axonal degeneration
      or by changes in norepinephrine reuptake.

PMID- 16815979
TI  - Loss of alpha2B-adrenoceptors increases magnitude of hypertension following
      nitric oxide synthase inhibition.
AB  - Vascular alpha(2B)-adrenoceptors (alpha(2B)-AR) may mediate vasoconstriction and
      contribute to the development of hypertension. Therefore, we hypothesized that
      blood pressure would not increase as much in mice with mutated alpha(2B)-AR as in
      wild-type (WT) mice following nitric oxide (NO) synthase (NOS) inhibition with
      N(omega)-nitro-l-arginine (l-NNA, 250 mg/l in drinking water). Mean arterial
      pressure (MAP) was recorded in heterozygous (HET) alpha(2B)-AR knockout mice and
      WT littermates using telemetry devices for 7 control and 14 l-NNA treatment days.
      MAP in HET mice was increased significantly on treatment days 1 and 4 to 14,
      whereas MAP did not change in WT mice (days 0 and 14 = 113 +/- 3 and 114 +/- 4
      mmHg in WT, 108 +/- 0.3 and 135 +/- 13 mmHg in HET, P < 0.05). MAP was
      significantly higher in HET than in WT mice days 10 through 14 (P < 0.05). Thus
      blood pressure increased more rather than less in mice with decreased alpha(2B)
      AR expression. We therefore examined constrictor responses to phenylephrine (PE,
      10(-9) to 10(-4) M) with and without NOS inhibition to determine basal NO
      contributions to arterial tone. In small pressurized mesenteric arteries (inner
      diameter = 177 +/- 5 microm), PE constriction was decreased in untreated HET
      arteries compared with WT (P < 0.05). l-NNA (100 microM) augmented PE
      constriction more in HET arteries than in WT arteries, and responses were not
      different between groups in the presence of l-NNA. Acetylcholine dilated
      preconstricted arteries from HET mice more than arteries from WT mice.
      Endothelial NOS expression was increased in HET compared with WT mesenteric
      arteries by Western analysis. Griess assay showed increased NO(x) concentrations
      in HET plasma compared with those in WT plasma. These data demonstrate that
      diminished alpha(2B)-AR expression increases the dependence of arterial pressure
      and vascular tone on NO production and that vascular alpha(2B)-AR either directly
      or indirectly regulates vascular endothelial NOS function.

PMID- 16815980
TI  - Molecular and electrophysiological characteristics of K+ conductance sensitive to
      acidic pH in aortic smooth muscle cells of WKY and SHR.
AB  - Changes in K(+) conductances and their contribution to membrane depolarization in
      the setting of an acidic pH environment have been studied in myocytes from aortic
      smooth muscle cells of spontaneously hypertensive rats (SHR) compared with those
      from Wistar-Kyoto (WKY) rats. The resting membrane potential (RMP) of aortic
      smooth muscle at extracellular pH (pH(o)) of 7.4 was significantly more
      depolarized in SHR than in WKY rats. Acidification to pH(o) 6.5 made this
      difference in RMP between SHR and WKY rats more significant by further
      depolarizing the SHR myocytes. Large-conductance Ca(2+)-activated K(+) (BK)
      currents, which were markedly suppressed by acidification, were larger in aortic
      myocytes of SHR than in those of WKY rats. In contrast, acid-sensitive, non-BK
      currents were smaller in SHR. Western blot analyses showed that expression of BK
      alpha- and -beta(1) subunits in SHR aortas was upregulated and comparable with
      those in WKY rats, respectively. Additional electrophysiological and molecular
      studies showed that pH- and halothane-sensitive two-pore domain weakly inward
      rectifying K(+) channel (TWIK)-like acid-sensitive K(+) (TASK) channel subtypes
      were functionally expressed in aortas, and TASK1 expression was significantly
      higher in WKY than in SHR. Although the background current through TASK channels
      at normal pH(o) (7.4) was small and may not contribute significantly to the
      regulation of RMP, TASK channel activation by halothane or alkalization (pH(o)
      8.0) induced significant hyperpolarization in WKY but not in SHR. In conclusion,
      the larger depolarization and subsequent abnormal contractions after
      acidification in aortic myocytes in the setting of SHR hypertension are mainly
      attributable to the larger contribution of BK current to the total membrane
      conductance than in WKY aortas.

PMID- 16815981
TI  - Gonadectomy prevents endothelial dysfunction in fructose-fed male rats, a factor
      contributing to the development of hypertension.
AB  - Insulin resistance has been shown to be associated with increased blood pressure
      (BP). The sex hormones estrogen and testosterone have opposing effects in the
      development of increased BP. Since testosterone has been implicated in increased
      BP following insulin resistance, we have tried to dissect out the effects of
      insulin resistance on endothelium-dependent vasorelaxation in the presence and
      absence of testosterone. Both gonadectomized and sham-operated male Wistar rats
      fed with a high-fructose diet developed insulin resistance, but BP increased only
      in the sham-operated rats. Reintroduction of testosterone in vivo restored the
      increase in BP, thereby abolishing the protective effects of gonadectomy.
      Fructose feeding did not affect plasma testosterone levels. Insulin resistance
      induced endothelial dysfunction in the mesenteric arteries of sham-operated rats,
      which was prevented by gonadectomy, thus suggesting a key role for testosterone
      in the pathogenesis of secondary vascular complications. Subsequent to blocking
      the actions of endothelium-dependent hyperpolarizing factor (EDHF), relaxation to
      acetylcholine (ACh) was lower in sham-operated fructose-fed rats compared with
      other groups, suggesting the involvement of nitric oxide (NO) in vasorelaxation.
      Inhibition of NO synthesis nearly abolished the ACh-evoked relaxation in both
      fructose-fed groups, thus suggesting a testosterone-independent impairment of
      EDHF-mediated relaxation. The improvement in endothelial function following
      gonadectomy could be ascribed to a NO component, although plasma nitrite and
      nitrate levels were unchanged. In summary, testosterone is essential in vivo for
      the development of endothelial dysfunction and hypertension secondary to insulin
      resistance, suggesting a facilitatory role for testosterone in increasing BP in
      fructose-fed male rats.

PMID- 16815982
TI  - Left ventricular myofilament dysfunction in rat experimental hypertrophy and
      congestive heart failure.
AB  - It is currently unclear whether left ventricular (LV) myofilament function is
      depressed in experimental LV hypertrophy (LVH) or congestive heart failure (CHF).
      To address this issue, we studied pressure overload-induced LV hypertrophy
      (POLVH) and myocardial infarction-elicited congestive heart failure (MICHF) in
      rats. LV myocytes were isolated from control, POLVH, and MICHF hearts by
      mechanical homogenization, skinned with Triton, and attached to micropipettes
      that projected from a sensitive force transducer and high-speed motor. A subset
      of cells was treated with either unphosphorylated, recombinant cardiac troponin
      (cTn) or cTn purified from either control or failing ventricles. LV myofilament
      function was characterized by the force-[Ca(2+)] relation yielding Ca(2+)
      saturated maximal force (F(max)), myofilament Ca(2+) sensitivity (EC(50)), and
      cooperativity (Hill coefficient, n(H)) parameters. POLVH was associated with a
      35% reduction in F(max) and 36% increase in EC(50). Similarly, MICHF resulted in
      a 42% reduction in F(max) and a 30% increase in EC(50). Incorporation of
      recombinant cTn or purified control cTn into failing cells restored myofilament
      Ca(2+) sensitivity toward levels observed in control cells. In contrast,
      integration of cTn purified from failing ventricles into control myocytes
      increased EC(50) to levels observed in failing myocytes. The F(max) parameter was
      not markedly affected by troponin exchange. cTnI phosphorylation was increased in
      both POLVH and MICHF left ventricles. We conclude that depressed myofilament
      Ca(2+) sensitivity in experimental LVH and CHF is due, in part, to a decreased
      functional role of cTn that likely involves augmented phosphorylation of cTnI.

PMID- 16815984
TI  - Physiological severity of coronary artery stenosis.

PMID- 16815983
TI  - Adenosine A2A receptor modulation of juvenile female rat skeletal muscle
      microvessel permeability.
AB  - Little is known of the regulation of skeletal muscle microvascular exchange under
      resting or stimulating conditions. Adenosine (ADO) levels in skeletal muscle
      increase during physiological (exercise) and pathological (hypoxia, inflammation,
      and ischemia) conditions. Later stages of these pathologies are characterized by
      the loss of vascular barrier integrity. This study focused on determining which
      ADO receptor mediates the robust reduction in microvessel permeability to rat
      serum albumin (P(s)(RSA)) observed in juvenile female rats. In microvessels
      isolated from abdominal skeletal muscle, ADO suffusion induced a concentration
      dependent reduction in arteriolar [log(IC(50)) = -9.8 +/- 0.2 M] and venular
      [log(IC(50)) = -8.4 +/- 0.2 M] P(s)(RSA). RT-PCR and immunoblot analysis
      demonstrated mRNA and protein expression of ADO A(1), A(2A), A(2B), and A(3)
      receptors in both vessel types, and immunofluorescence assay revealed expression
      of the four subtype receptors in the microvascular walls (endothelium and smooth
      muscle). P(s)(RSA) responses of arterioles and venules to ADO were blocked by 8
      (p-sulphophenyl)theophylline, a nonselective A(1) and A(2) antagonist. An A(2A)
      agonist, CGS21680, was more potent than the A(1) agonist, cyclopentyladenosine,
      or the most-selective A(2B) agonist, 5'-(N-ethylcarboxamido)adenosine. The
      ability of CGS21680 or ADO to reduce P(s)(RSA) was abolished by the A(2A)
      antagonist, ZM241385. An adenylyl cyclase inhibitor, SQ22536, blocked the
      permeability response to ADO. In aggregate, these results demonstrate that, in
      juvenile females (before the production of the reproductive hormones), ADO
      enhances skeletal muscle arteriole and venule barrier function predominantly via
      A(2A) receptors using activation of adenylyl cyclase-signaling mechanisms.

PMID- 16815985
TI  - Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions
      containing connexins 37 and 40.
AB  - Control of cerebral vasculature differs from that of systemic vessels outside the
      blood-brain barrier. The hypothesis that the endothelium modulates vasomotion via
      direct myoendothelial coupling was investigated in a small vessel of the cerebral
      circulation. In the primary branch of the rat basilar artery, membrane potential,
      diameter, and calcium dynamics associated with vasomotion were examined using
      selective inhibitors of endothelial function in intact and endothelium-denuded
      arteries. Vessel anatomy, protein, and mRNA expression were studied using
      conventional electron microscopy high-resolution ultrastructural and confocal
      immunohistochemistry and quantitative PCR. Membrane potential oscillations were
      present in both endothelial cells and smooth muscle cells (SMCs), and these
      preceded rhythmical contractions during which adjacent SMC intracellular calcium
      concentration ([Ca(2+)](i)) waves were synchronized. Endothelium removal
      abolished vasomotion and desynchronized adjacent smooth muscle cell [Ca(2+)](i)
      waves. N(G)-nitro-l-arginine methyl ester (10 microM) did not mimic this effect,
      and dibutyryl cGMP (300 muM) failed to resynchronize [Ca(2+)](i) waves in
      endothelium-denuded arteries. Combined charybdotoxin and apamin abolished
      vasomotion and depolarized and constricted vessels, even in absence of
      endothelium. Separately, (37,43)Gap27 and (40)Gap27 abolished vasomotion.
      Extensive myoendothelial gap junctions (3 per endothelial cell) composed of
      connexins 37 and 40 connected the endothelial cell and SMC layers. Synchronized
      vasomotion in rat basilar artery is endothelium dependent, with [Ca(2+)](i) waves
      generated within SMCs being coordinated by electrical coupling via myoendothelial
      gap junctions.

PMID- 16815986
TI  - Cardioprotection by postconditioning in conscious rats is limited to coronary
      occlusions <45 min.
AB  - OBJECTIVES: Brief episodes of ischemia and reperfusion after a lethal ischemic
      insult confer cardioprotection, a phenomenon termed "ischemic postconditioning."
      However, all studies reported to date have been conducted in open-chest animal
      models. We sought to determine whether postconditioning occurs in conscious
      animals and whether it protects against severe myocardial injury. METHODS:
      Chronically instrumented rats were assigned to a 30- (Subset 1), 45- (Subset 2),
      or 60-min (Subset 3) coronary occlusion followed by 24 h of reperfusion. In each
      subset, rats received no further intervention (control), were preconditioned with
      12 cycles of 2-min occlusion/2-min reperfusion immediately (early
      preconditioning; EPC) or 24 h (late preconditioning; LPC) before myocardial
      infarction, or were postconditioned with 20 cycles of 10-s occlusion/10-s
      reperfusion immediately after myocardial infarction (20-10 PostC). RESULTS: With
      a 30-min occlusion, infarct size (54.4 +/- 2.3% of risk region in control-30) was
      significantly reduced in EPC-30, LPC-30, and 20-10 PostC-30 groups (by 72, 70,
      and 47%, respectively; all P < 0.05 vs. control-30). With a 45-min occlusion,
      infarct size (62.2 +/- 2.4% in control-45) was reduced in EPC-45 and LPC-45
      groups (by 47 and 41%, respectively; all P < 0.05 vs. control-45) but not in the
      20-10 PostC-45 group [55.4 +/- 2.3%, P = not significant (NS) vs. control-45].
      With a 60-min occlusion, infarct size (72.7 +/- 2.2% in control-60) was reduced
      in the EPC-60 (by 20%, P < 0.05) but not in the LPC-60 (63.6 +/- 2.5%, P = NS) or
      in the 20-20 PostC group (71.5 +/- 3.4%, P = NS). CONCLUSIONS: Both early and
      late ischemic preconditioning as well as ischemic postconditioning confer
      protection in conscious rats; however, unlike early preconditioning,
      postconditioning protects only against coronary occlusions <45 min. In the
      conscious rat, the cardioprotection afforded by postconditioning is limited to
      mild to moderate myocardial injury.

PMID- 16815987
TI  - The monosialosyl ganglioside GM-1 reduces the vagolytic efficacy of delta2-opioid
      receptor stimulation.
AB  - The cardiac enkephalin, methionine-enkephalin-arginine-phenylalanine (MEAP),
      alters vagally induced bradycardia when introduced by microdialysis into the
      sinoatrial (SA) node. The responses to MEAP are bimodal; lower doses enhance
      bradycardia and higher doses suppress bradycardia. The opposing vagotonic and
      vagolytic effects are mediated, respectively, by delta(1) and delta(2) phenotypes
      of the same receptor. Stimulation of the delta(1) receptor reduced the subsequent
      delta(2) responses. Experiments were conducted to test the hypothesis that the
      delta-receptor interactions were mediated by the monosialosyl ganglioside GM-1.
      When the mixed agonist MEAP was evaluated after nodal GM-1 treatment, delta(1)
      mediated vagotonic responses were enhanced, and delta(2)-mediated vagolytic
      responses were reduced. Prior treatment with the delta(1)-selective antagonist 7
      benzylidenaltrexone (BNTX) failed to prevent attrition of the delta(2)-vagolytic
      response or restore it when added afterward. Thus the GM-1-mediated attrition was
      not mediated by delta(1) receptors or increased competition from delta(1)
      mediated vagotonic responses. When GM-1 was omitted, deltorphin produced a
      similar but less robust loss in the vagolytic response. In contrast, however, to
      GM-1, the deltorphin-mediated attrition was prevented by pretreatment with BNTX,
      indicating that the decline in response after deltorphin alone was mediated by
      delta(1) receptors and that GM-1 effectively bypassed the receptor. Whether
      deltorphin has intrinsic delta(1) activity or causes the release of an endogenous
      delta(1)-agonist is unclear. When both GM-1 and deltorphin were omitted, the
      subsequent vagolytic response was more intense. Thus GM-1, deltorphin, and time
      all interact to modify subsequent delta(2)-mediated vagolytic responses. The data
      support the hypothesis that delta(1)-receptor stimulation may reduce delta(2)
      vagolytic responses by stimulating the GM-1 synthesis.

PMID- 16815988
TI  - Exercise metaboreflex activation and endothelial function impairment in atrial
      fibrillation.
AB  - Exercising muscle hypoperfusion stimulates afferents (metaboreceptors) involved
      in the regulation of ventilation. Atrial fibrillation (AF), particularly when
      combined with diseases causing endothelial (ED) impairment, such as hypertension
      (HP) and diabetes mellitus (DM), depresses the ED activity and enhances exercise
      hyperventilation. The relationship between these two functions and the underlying
      mechanisms have not been explored previously. In lone AF or AF associated with HP
      or DM (12 subjects in each cohort), we investigated the brachial artery flow
      mediated dilatation (ED function) and ventilation during the recovery phase of
      handgrip (metaboreflex) exercise for subjects receiving placebo or oral vitamin C
      (double-blind crossover), both before and after cardioversion (CV) to sinus
      rhythm. Baseline ED impairment was increasingly more severe and the ergoreflex
      activity more pronounced in AF + HP and AF + DM compared with lone AF. Vitamin C
      and CV significantly improved both flow-mediated dilatation and metaboreflex
      activity in lone AF and AF + HP, and vitamin C did not produce any additive
      effect when administered after CV. In AF + DM, neither vitamin C nor CV was
      effective. This study provides the following information: AF generates oxidative
      injury, which is less when the arrhythmia is lone AF and greater when the
      arrhythmia is associated with HP. In DM, the oxidative injury generated by AF is
      refractory to a rather weak antioxidant, like vitamin C, or the baseline damage
      is such as to prevent any additive influence of AF. In AF, a cause-effect link
      exists between ED dysfunction and metaboreflex activity. Ventilatory advantages
      of CV seem to be inversely related with the extension of the underlying ED
      oxidative impairment.

PMID- 16815989
TI  - Effect of cigarette smoking on nitric oxide, structural, and mechanical
      properties of mouse arteries.
AB  - Cigarette smoking (CS) is a major risk factor for vascular disease. The aim of
      this study was to quantitatively assess the influence of CS on mouse arteries. We
      studied the effect of short-term (6 wk) and long-term (16 wk) CS exposure on
      structural and mechanical properties of coronary arteries compared with that of
      control mice. We also examined the reversibility of the deleterious effects of CS
      on structural [e.g., wall thickness (WT)], mechanical (e.g., stiffness), and
      biochemical [e.g., nitric oxide (NO) by-products] properties with the cessation
      of CS. The left and right coronary arteries were cannulated in situ and
      mechanically distended. The stress, strain, elastic modulus, and WT of coronary
      arteries were determined. Western blot analysis was used to analyze endothelial
      NO synthase (eNOS) in the femoral and carotid arteries of the same mice, and NO
      by-products were determined by measuring the levels of nitrite. Our results show
      that the mean arterial pressure was increased by CS. Furthermore, CS
      significantly increased the elastic modulus, decreased stress and strain, and
      increased the WT and WT-to-radius ratio compared with those of control mice. The
      reduction of eNOS protein expression was found only after long-term CS exposure.
      Moreover, the NO metabolite was markedly decreased in CS mice after short- and
      long-term exposure of CS. These findings suggest that 16 wk of CS exposure can
      cause an irreversible deterioration of structural and elastic properties of mouse
      coronary arteries. The decrease in endothelium-derived NO in CS mice was seen to
      significantly correlate with the remodeling of arterial wall.

PMID- 16815990
TI  - Peppermint oil.

PMID- 16815991
TI  - Newborn resuscitation.

PMID- 16815992
TI  - Biliary atresia.

PMID- 16815993
TI  - Mental retardation: management and prognosis.

PMID- 16815994
TI  - Late effects in survivors of childhood cancer.

PMID- 16815995
TI  - Consultation with the specialist: patellofemoral conditions in childhood.

PMID- 16815996
TI  - Index of suspicion.

PMID- 16815998
TI  - mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and
      DCP1:DCP2 decapping complexes.
AB  - MicroRNAs (miRNAs) silence the expression of target genes post-transcriptionally.
      Their function is mediated by the Argonaute proteins (AGOs), which colocalize to
      P-bodies with mRNA degradation enzymes. Mammalian P-bodies are also marked by the
      GW182 protein, which interacts with the AGOs and is required for miRNA function.
      We show that depletion of GW182 leads to changes in mRNA expression profiles
      strikingly similar to those observed in cells depleted of the essential
      Drosophila miRNA effector AGO1, indicating that GW182 functions in the miRNA
      pathway. When GW182 is bound to a reporter transcript, it silences its
      expression, bypassing the requirement for AGO1. Silencing by GW182 is effected by
      changes in protein expression and mRNA stability. Similarly, miRNAs silence gene
      expression by repressing protein expression and/or by promoting mRNA decay, and
      both mechanisms require GW182. mRNA degradation, but not translational
      repression, by GW182 or miRNAs is inhibited in cells depleted of CAF1, NOT1, or
      the decapping DCP1:DCP2 complex. We further show that the N-terminal GW repeats
      of GW182 interact with the PIWI domain of AGO1. Our findings indicate that GW182
      links the miRNA pathway to mRNA degradation by interacting with AGO1 and
      promoting decay of at least a subset of miRNA targets.

PMID- 16815997
TI  - The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling
      pathway.
AB  - MACF1 (microtubule actin cross-linking factor 1) is a multidomain protein that
      can associate with microfilaments and microtubules. We found that MACF1 was
      highly expressed in neuronal tissues and the foregut of embryonic day 8.5 (E8.5)
      embryos and the head fold and primitive streak of E7.5 embryos. MACF1(-/-) mice
      died at the gastrulation stage and displayed developmental retardation at E7.5
      with defects in the formation of the primitive streak, node, and mesoderm. This
      phenotype was similar to Wnt-3(-/-) and LRP5/6 double-knockout embryos. In the
      absence of Wnt, MACF1 associated with a complex that contained Axin, beta
      catenin, GSK3beta, and APC. Upon Wnt stimulation, MACF1 appeared to be involved
      in the translocation and subsequent binding of the Axin complex to LRP6 at the
      cell membrane. Reduction of MACF1 with small interfering RNA decreased the amount
      of beta-catenin in the nucleus, and led to an inhibition of Wnt-induced TCF/beta
      catenin-dependent transcriptional activation. Similar results were obtained with
      a dominant-negative MACF1 construct that contained the Axin-binding region.
      Reduction of MACF1 in Wnt-1-expressing P19 cells resulted in decreased T
      (Brachyury) gene expression, a DNA-binding transcription factor that is a direct
      target of Wnt/beta-catenin signaling and required for mesoderm formation. These
      results suggest a new role of MACF1 in the Wnt signaling pathway.

PMID- 16815999
TI  - An MMP liberates the Ninjurin A ectodomain to signal a loss of cell adhesion.
AB  - Matrix metalloproteinases (MMPs) are important for developmental tissue
      remodeling and for the inflammatory response. Although the vertebrate MMP family
      is large and functionally redundant, the fruitfly Drosophila melanogaster has
      only two MMPs, both essential genes. Our previous work demonstrated that Mmp1 is
      required for growth of the tracheal system, and we suggested that the mutant
      phenotype resulted from aberrant persistence of cell adhesion to the
      extracellular matrix. Here we report the identification of NijA, a transmembrane
      protein whose vertebrate homologs regulate cell adhesion, as a two-hybrid binding
      partner for Mmp1. The binding of Mmp1 and NijA was confirmed by
      coimmunoprecipitation of endogenous proteins from flies, and the endogenous
      proteins were found to colocalize at the tracheal cell surface in larvae. When
      NijA is expressed in S2 cells, they lose adhesion to surfaces; this adhesion-loss
      phenotype is dependent on the expression and catalytic activity of Mmp1. Our data
      indicate that Mmp1 releases the N-terminal extracellular domain of NijA. This
      liberated ectodomain promotes the loss of cell adhesion in a cell-nonautonomous
      manner. We suggest that tracheal cell adhesion is regulated by a novel mechanism
      utilizing an MMP and a ninjurin family member.

PMID- 16816000
TI  - Evidence for a novel protease governing regulated intramembrane proteolysis and
      resistance to antimicrobial peptides in Bacillus subtilis.
AB  - Evidence is presented that the activation of the RNA polymerase sigma factor
      sigma(W) in Bacillus subtilis by regulated intramembrane proteolysis is governed
      by a novel, membrane-embedded protease. The sigma(W) factor is activated by
      proteolytic destruction of the membrane-bound anti-sigma(W) factor RsiW in
      response to antimicrobial peptides and other agents that damage the cell
      envelope. RsiW is destroyed by successive proteolytic events known as Site-1 and
      Site-2 cleavage. Site-2 cleavage is mediated by a member of the SpoIVFB-S2P
      family of intramembrane-acting metalloproteases, but the protease responsible for
      Site-1 cleavage was unknown. We have identified a previously uncharacterized,
      multipass membrane protein called PrsW (annotated YpdC) that is both necessary
      and sufficient (when artificially produced in an unrelated host bacterium) for
      Site-1 cleavage of RsiW. PrsW is a member of a widespread family of membrane
      proteins that includes at least one previously known protease. We identify
      residues important for proteolysis and a cluster of acidic residues involved in
      sensing antimicrobial peptides and cell envelope stress.

PMID- 16816001
TI  - Drosophila ribosomal proteins are associated with linker histone H1 and suppress
      gene transcription.
AB  - The dynamics and function of ribosomal proteins in the cell nucleus remain
      enigmatic. Here we provide evidence that specific components of Drosophila
      melanogaster ribosomes copurify with linker histone H1. Using various
      experimental approaches, we demonstrate that this association of nuclear
      ribosomal proteins with histone H1 is specific, and that colocalization occurs on
      condensed chromatin in vivo. Chromatin immunoprecipitation analysis confirmed
      that specific ribosomal proteins are associated with chromatin in a histone H1
      dependent manner. Overexpression of either histone H1 or ribosomal protein L22 in
      Drosophila cells resulted in global suppression of the same set of genes, while
      depletion of H1 and L22 caused up-regulation of tested genes, suggesting that H1
      and ribosomal proteins are essential for transcriptional gene repression.
      Overall, this study provides evidence for a previously undefined link between
      ribosomal proteins and chromatin, and suggests a role for this association in
      transcriptional regulation in higher eukaryotes.

PMID- 16816002
TI  - Expression profile of CBF-like transcriptional factor genes from Eucalyptus in
      response to cold.
AB  - Two CBF (CRT/DRE-binding factor) homologues isolated from Eucalyptus gunnii were
      designated EguCBF1a and EguCBF1b and belong to a gene family which includes at
      least five members. Both promoter and coding sequences were found to exhibit the
      main characteristics of a CBF transcription activator gene and, as expected, the
      corresponding protein targeted the nucleus. Gene expression was quantitatively
      analysed using real-time reverse transcription-polymerase chain reaction (RT-PCR)
      after a short exposure to different environmental conditions or along a two-step
      cold acclimation programme with either short or long daylengths. A very strong
      and fast response to cold was observed, with dark conditions and cold intensity
      (down to 0 degrees C) having a positive effect on the magnitude of induction. The
      two genes under study exhibited several similar features such as light response.
      However, interestingly, their regulation by cold proved differential and
      complementary as EguCBF1a was more transiently induced by a direct and intense
      exposure while EguCBF1b responded to milder treatments and exhibited a longer
      (i.e. which started earlier and finished later) time course. During acclimation,
      the short daylength positively affected the freezing tolerance in the same way as
      it positively affected the CBF transcript accumulation, suggesting a potential
      involvement of these genes in the adaptive response. Although very quick after
      the first signal, the up-regulation of the two EguCBF1 genes unexpectedly lasted
      throughout the chilling culture, and new inductions were seen during the
      thermoperiod transitions. Using a quantitative and highly sensitive measurement
      of gene expression combined with the application of a cold treatment consistent
      with natural environmental conditions, this study provides new information on the
      regulation of CBF-like genes by cold in planta.

PMID- 16816003
TI  - Immunizations for patients with metabolic disorders.
AB  - Individuals with underlying metabolic disorders are a potential high-risk group
      for vaccine-preventable diseases. Newborn metabolic screening has provided a
      means of early identification and treatment for many of these disorders, whereas
      childhood immunization is one of the most effective means of decreasing the
      morbidity and mortality resulting from communicable diseases worldwide. There are
      very few contraindications to the routine administration of vaccines to the
      healthy, immunocompetent individual. In certain high-risk groups, such as
      immunocompromised patients, gravid females, and those with a history of previous
      anaphylactic reaction to a vaccine or its components, selective withholding of
      immunizations must be considered to decrease potential adverse events. A detailed
      analysis of the medical literature revealed few specific recommendations
      regarding appropriate immunization techniques for patients with metabolic
      disorders. In this review we detail the major metabolic disorder subtypes,
      elaborate on the available literature on immunizations for patients with these
      disorders, and provide suggested vaccine recommendations.

PMID- 16816004
TI  - Intracranial hemorrhage as the initial manifestation of a congenital disorder of
      glycosylation.
AB  - Intracranial hemorrhage in a term neonate is a rare event in the absence of an
      identifiable precipitating factor such as severe thrombocytopenia, mechanical
      trauma, asphyxia, infections, or congenital vascular malformations. Congenital
      disorders of glycosylation are a genetically and clinically heterogeneous group
      of multisystem disorders characterized by the abnormal glycosylation of a number
      of glycoproteins. Although bleeding caused by abnormal glycosylation of various
      coagulation factors is a well-known clinical complication of several types of
      congenital disorders of glycosylation, intracranial hemorrhage has not been
      reported as an initial manifestation of this entity. Here we report the detailed
      history of a family with 2 consecutive male infants, both born at term with
      intracranial hemorrhage diagnosed within the first 24 hours of life. The
      diagnosis of a congenital disorder of glycosylation was established in the second
      infant by an abnormal glycosylation of serum transferrin detected by electrospray
      ionization mass spectrometry. Both infants showed significant neurologic
      deterioration during the first month of life, and both died at 5 months of age.
      Intracranial hemorrhage in a term neonate without a potential precipitating
      factor represents yet another clinical feature that should raise the suspicion
      for a congenital disorder of glycosylation.

PMID- 16816005
TI  - Topical voriconazole solution for cutaneous aspergillosis in a pediatric patient
      after bone marrow transplant.
AB  - Invasive aspergillosis seems to be on the rise, especially in immunocompromised
      children. Historically, only systemic amphotericin B has been effective against
      Aspergillus. Development of newer antifungal agents, such as voriconazole and
      caspofungin, has improved the treatment options available for aspergillosis,
      although no definitive management strategy has been established. Here we describe
      the use of topical voriconazole combined with systemic antifungal agents for
      cutaneous aspergillosis in a pediatric patient after bone marrow transplant.

PMID- 16816006
TI  - Schimke versus non-Schimke chronic kidney disease: an anthropometric approach.
AB  - Schimke-immuno-osseous dysplasia is a rare autosomal-recessive multisystem
      disorder with the main clinical features of disproportionate growth deficiency,
      defective cellular immunity, and progressive renal disease. It is caused by
      mutations of SMARCAL1, a gene encoding a putative chromatin remodeling protein of
      unknown function. Because a detailed description of the clinical features is an
      essential first step in elucidating the function of SMARCAL1, we present the
      first detailed anthropometric data for Schimke-immuno-osseous dysplasia patients.
      By comprehensive anthropometric examination (28 parameters) of 8 patients (3
      females) with the typical findings of Schimke-immuno-osseous dysplasia (mean age:
      14.8 years; range: 4.9-30.5 years) and 304 patients (117 females) with congenital
      and hereditary chronic kidney disease (mean age: 10.7 +/- 4.8 years; range: 3
      21.8 years), we show that Schimke-immuno-osseous dysplasia patients differ
      significantly from those with other forms of chronic kidney disease. z scores
      were calculated with reference limits derived from 5155 healthy children (2591
      females) aged 3 to 18 years. The key finding was that, in the latter group,
      median leg length was significantly more reduced than sitting height, whereas in
      Schimke-immuno-osseous dysplasia patients, the reduction of sitting height was
      significantly more pronounced than for leg length. Therefore, the ratio of
      sitting height/leg length might be a simple tool for the clinician to distinguish
      Schimke-immuno-osseous dysplasia from other chronic kidney disease patients.
      Schimke-immuno-osseous dysplasia is very likely if this ratio is < 0.83. However,
      other forms of chronic kidney disease have to be discussed in case of a ratio >
      1.01.

PMID- 16816007
TI  - Successful parental use of an automated external defibrillator for an infant with
      long-QT syndrome.
AB  - Congenital long-QT syndrome with 2:1 atrioventricular block presenting in the
      perinatal period is rare, has a poor prognosis, and leads to high risk for lethal
      ventricular arrhythmic events. An implantable cardioverter-defibrillator seems to
      be the most effective treatment in the prevention of arrhythmic sudden cardiac
      death in patients with long-QT syndrome. Technical limitations and risks
      associated with implantable cardioverter-defibrillators in asymptomatic infants
      is considered too great to justify use for primary prophylaxis against sudden
      cardiac death. In this case report we describe the first successful parental use
      of an automated external defibrillator prescribed for primary prophylaxis against
      sudden cardiac death in an infant with long-QT syndrome.

PMID- 16816009
TI  - Position statement of the American Association for Geriatric Psychiatry regarding
      principles of care for patients with dementia resulting from Alzheimer disease.

PMID- 16816010
TI  - Phenomenology and clinical correlates of delusions in Alzheimer disease.
AB  - OBJECTIVES: The objectives of this study were to determine whether anosognosia,
      depression, and elevated mood are associated with delusions in Alzheimer disease
      (AD), and to examine the validity of standardized diagnostic criteria for
      psychosis of dementia. METHOD: The authors assessed a consecutive series of 771
      patients with AD attending a dementia clinic with a comprehensive
      neuropsychologic and psychiatric evaluation that included specific measures of
      delusions, hallucinations, anosognosia, depression, and elevated mood. RESULTS:
      Delusions were found in one-third of the patients and hallucinations in 7%. Most
      patients with hallucinations also had delusions. A principal component analysis
      of the Psychosis Dementia Scale, which rates the presence and severity of
      delusions, produced the factors of paranoid misidentification and expansive
      delusions. Paranoid, but not expansive, delusions increased across the stages of
      the illness. Anosognosia and depression were significantly and independently
      associated with the presence of delusions, whereas elevated mood was
      significantly associated with expansive, but not paranoid, delusions. A multiple
      logistic regression analysis demonstrated that delusions in AD were significantly
      associated with depression, anosognosia, overt aggression, and agitation.
      CONCLUSIONS: Anosognosia, depression, global cognitive deficits, and elevated
      mood are the main psychiatric correlates of paranoid misidentification and
      expansive delusions in AD, whereas overt aggression and agitation are the most
      frequent behavioral concomitants of psychosis in AD.

PMID- 16816011
TI  - More severe functional impairment in dementia with lewy bodies than Alzheimer
      disease is related to extrapyramidal motor dysfunction.
AB  - OBJECTIVE: The objective of this study was to compare functional impairments in
      dementia with Lewy bodies (DLB) and Alzheimer disease (AD) and their relationship
      with motor and neuropsychiatric symptoms. METHODS: The authors conducted a cross
      sectional study of 84 patients with DLB or AD in a secondary care setting.
      Patients were diagnosed according to published criteria for DLB and AD. The
      Bristol Activities of Daily Living Scale (BADLS) was used to assess functional
      impairments. Participants were also assessed using the Unified Parkinson's
      Disease Rating Scale (motor section), the Neuropsychiatric Inventory, and the
      Mini-Mental Status Examination. RESULTS: Patients with DLB were more functionally
      impaired and had more motor and neuropsychiatric difficulties than patients with
      AD with similar cognitive scores. In both AD and DLB, there were correlations
      between total BADLS scores and motor and neuropsychiatric deficits. There was
      more impairment in the mobility and self-care components of the BADLS in DLB than
      in AD, and in DLB, these were highly correlated with UPDRS score. In AD,
      orientation and instrumental BADLS components were most affected. CONCLUSION: The
      nature of functional disability differs between AD and DLB with additional
      impairments in mobility and self-care in DLB being mainly attributable to
      extrapyramidal motor symptoms. Consideration of these is important in assessment
      and management. Activities of daily living scales for use in this population
      should attribute the extent to which functional disabilities are related to
      cognitive, psychiatric, or motor dysfunction.

PMID- 16816012
TI  - Comparison of different clinical diagnostic criteria for depression in Alzheimer
      disease.
AB  - OBJECTIVE: Data in the literature show different estimates of the prevalence of
      depression in patients with Alzheimer disease (AD) when different classification
      systems are used. This study describes the prevalence and clinical features of
      depression in AD based on five different depression classification systems.
      METHODS: This was a cross-sectional, observational study of 491 patients with
      probable AD. Depression was diagnosed using five classification systems
      (International Classification of Diseases, 10th Revision [ICD-10], Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV], Cambridge
      Examination for Mental Disorder of the Elderly [CAMDEX], Provisional Diagnostic
      Criteria for depression in AD [PDC-dAD], Neuropsychiatric Inventory [NPI]).
      RESULTS: The prevalence of depression was 4.9% (95% confidence interval [CI]: 3.2
      7.1) according to ICD-10 criteria; 9.8% (95% CI: 7.3-12.6) according to CAMDEX;
      13.4% (95% CI: 10.6-16.6) according to DSM-IV; 27.4% (95% CI: 23.6-31.5)
      according to PDC-dAD criteria; and 43.7% (95% CI: 39.4-48.2) when using the
      screening questions from the NPI depression subscale. The level of agreement
      between the classification systems was low to moderate (kappa <0.52). The
      characteristics associated with the most diagnostic disagreement were loss of
      confidence or self-esteem and irritability. CONCLUSIONS: This study shows that
      there is a high variability in the prevalence rates of depression in AD depending
      on the diagnostic criteria used and that there is a low rate of agreement among
      the diagnostic criteria analyzed. The results suggest that the use of generic
      diagnostic criteria such as the ICD-10, the CAMDEX, or DSM-IV provides low
      prevalence rates of depression in patients with AD compared with specific
      diagnostic criteria such as the PDC-dAD.

PMID- 16816013
TI  - Frontal signal hyperintensities in mania in old age.
AB  - OBJECTIVE: Signal hyperintensities (SH) on magnetic resonance (MR) imaging have
      been associated with increased age and with mood disorders. Frontal and
      subcortical neuropathology has been implicated in the pathophysiology of mania
      and bipolar disorders. The authors assessed frontal and subcortical SH in elderly
      bipolar manic patients and the comparison group, and hypothesized that SH scores
      would be greater in the patient group. METHOD: MR imaging was performed in
      patients aged > or = 60 years with bipolar disorder, mania, and in a same-aged
      community comparison group. SH were rated blindly using the Boyko system. Frontal
      deep white matter and basal ganglia SH were assessed in the left and right
      hemispheres. RESULTS: SH scores were significantly greater in patients (N = 40)
      than the comparison group (N = 15) in frontal deep white matter (left: p = 0.003;
      right: p = 0.023) based on Mann-Whitney two-sample exact tests. The SH scores in
      the subcortical gray regions overlapped in these groups. In patients, higher
      right frontal SH scores were associated with later age at onset of mania.
      CONCLUSIONS: Frontal deep white matter SH may be increased in elders with bipolar
      disorder. Further study of the relationship of SH to age at onset in elders is
      warranted.

PMID- 16816014
TI  - Effects of donepezil on neuropsychiatric symptoms in patients with dementia and
      severe behavioral disorders.
AB  - OBJECTIVE: The objective of this study was to conduct exploratory analyses of
      data pertaining to the efficacy of donepezil treatment of patients with severe
      behavioral disturbances. Preliminary studies suggest that cholinesterase
      inhibitors, including donepezil, may reduce behavioral disturbances in patients
      with Alzheimer disease (AD). Most patients included in clinical trials have had
      low levels of psychopathology at baseline, and the effect of cholinesterase
      inhibitors on patients with more severe behavioral disturbances is unknown. The
      authors report the effects of donepezil on behavioral disturbances in patients
      with relatively severe psychopathology at baseline. METHODS: This is a hypothesis
      driven secondary analysis of a three-phase study involving donepezil and
      sertraline. In phase 1, psychotropic agents were withdrawn; in phase 2, patients
      were treated in an open-label fashion with donepezil for 8 weeks; and in phase 3,
      patients on donepezil were randomized to receive placebo or sertraline for an
      additional 12 weeks. The data set analyzed is comprised of the patient population
      treated with donepezil (without sertraline) for 20 weeks. One hundred twenty
      patients were included in the analyses. Mean age was 76 years, average Mini
      Mental State Examination Score was 18, and mean Neuropsychiatric Inventory (NPI)
      total score was 30. Primary efficacy assessments were the NPI, the Clinical
      Global Impression-Improvement, and the Clinical Global Impression-Severity
      scales. Secondary measures included the Behavioral Pathology in Alzheimer's
      Disease Rating Scale, The Hamilton Depression Rating Scale, and the Alzheimer's
      Disease Functional Assessment and Change Scale. RESULTS: Excellent concurrent
      validity was noted between the NPI and the Behavioral Pathology in Alzheimer's
      Disease Rating Scale. The total score of the NPI was significantly reduced over
      the 20 weeks of therapy with donepezil. Sixty-two percent of patients had at
      least a 30% reduction in the total NPI score (significantly greater than the
      number with no meaningful response). Likewise, more patients had total or partial
      resolution of depression and delusions than those who had no meaningful change.
      Factor analysis of baseline NPI data revealed five factors, including a psychosis
      factor, an agitation factor, mood factor, frontal lobe function factor, and
      appetite and eating disorders factor. Clinically meaningful treatment effect
      sizes were notable for the delusion factor (0.340) and the mood factor (0.39).
      There were significant correlations between the Clinical Global Impression
      Improvement and reductions in mood and agitation scores. CONCLUSION: The results
      of these analyses suggest that donepezil reduces behavioral symptoms,
      particularly mood disturbances and delusions, in patients with AD with relatively
      severe psychopathology.

PMID- 16816015
TI  - The relationship between psychiatric disorders and the ability to age in place in
      assisted living.
AB  - OBJECTIVE: Residential care/assisted living (RC/AL) has become a popular long
      term care option in the past decade, in part because these settings offer
      residents a more home-like environment than nursing homes (NHs) while still
      offering supervision and assistance to meet individuals' personal and healthcare
      needs. One of the goals of RC/AL is to facilitate residents' ability to age in
      place by providing access to needed services and thereby delaying NH admission.
      This article explores individual and facility-level characteristics associated
      with discharge from RC/AL to NH with particular attention to persons with a
      psychiatric disorder. METHODS: A Cox proportional hazards model was used to
      examine the risk factors associated with discharge from RC/AL to NH for a
      nonrandom sample of 366 residents in 37 RC/AL facilities in one state. RESULTS:
      Thirty-two percent of residents sampled had a psychiatric disorder. Residents
      with a psychiatric disorder were 1.78 times more likely to discharge to a NH.
      Other factors significantly associated with discharge from a RC/AL to NH included
      age (older), being married, more hospitalizations, for-profit ownership status,
      and part of a NH or continuing care retirement community. CONCLUSION: This
      article identifies both facility and individual characteristics that increase the
      likelihood of RC/AL residents discharging to NHs. Given that one of the main
      findings is that persons with a psychiatric disorder are at increased risk of
      discharge to NH, there is a need for improved provision of services for this
      population in RC/ALs to reduce premature discharge to NHs and to support aging in
      place in RC/ALs.

PMID- 16816016
TI  - Yearlong physical activity and depressive symptoms in older Japanese adults:
      cross-sectional data from the Nakanojo study.
AB  - OBJECTIVE: The objective of this study was to investigate associations between
      accelerometer measurements of physical activity and psychosocial variables in
      older people. METHODS: Subjects were 184 Japanese aged 65-85 years. An
      accelerometer provided step count and physical activity intensity data throughout
      each 24-hour period for 1 year. At the end of the year, anxiety, depression, and
      cognitive function were assessed. RESULTS: Controlling for age, the daily number
      of steps, and the daily duration of moderate-intensity physical activity showed
      significant negative correlations with depressive mood. CONCLUSION: A depressive
      mood is associated with the quantity and quality of habitual physical activity.

PMID- 16816017
TI  - Frontal dysfunction underlies depressive syndrome in Alzheimer disease: a FDG-PET
      study.
AB  - OBJECTIVE: This study aimed to investigate the regional cerebral dysfunction
      associated with depressive syndrome in patients with Alzheimer disease (AD).
      METHOD: Twelve patients with AD with depressive syndrome (ADD) and 12 age-,
      gender-, and severity-matched patients with AD without depressive syndrome (ADND)
      underwent FDG-PET scanning. The regional cerebral glucose metabolism in the two
      groups was compared using a voxel-based method. RESULTS: The ADD group showed
      lower glucose metabolism in the right superior frontal gyrus than the ADND group.
      CONCLUSIONS: These results indicate that frontal dysfunction, known to be
      associated with primary or other secondary depressive syndromes, underlies the
      depressive syndrome of patients with AD patients as well.

PMID- 16816018
TI  - Intramuscular ziprasidone treatment of acute psychotic agitation in elderly
      patients with schizophrenia.
AB  - OBJECTIVE: Intramuscular (i.m.) ziprasidone treatment has been shown to be
      effective and well tolerated in reducing the symptoms of acute psychosis in
      adults. Few data are available as to safety in the elderly. The growing
      utilization of health services by elderly psychiatric patients warrants an
      evaluation in this population. METHOD: Consecutive elderly patients (60 years of
      and older) admitted to a psychogeriatric ward in a large, university-affiliated
      tertiary psychiatric center were treated by i.m. ziprasidone for acute psychotic
      agitation. Patients received three days of flexible-dose i.m. ziprasidone. After
      an initial dose of 10-20 mg, a subsequent dose of 10-20 mg could be given after
      12 hours if needed (maximum daily dose: 40 mg). RESULTS: All treatment emergent
      side effects and adverse events along with the investigators' assessments of
      severity were systematically recorded as the primary outcome. The Brief
      Psychiatric Rating Scale (BPRS) and the Behavioral Activity Rating Scale (BARS)
      were the secondary outcomes. Twenty-one patients, six male and 15 female, mean
      age 71.4 +/- 1.3 years (range: 60-81 years) were enrolled. All had completed the
      three days i.m. ziprasidone treatment. There was one adverse event in a patient
      with untreated benign prostatic hypertrophy who developed urinary retention. Two
      side effects of mild severity that resolved spontaneously were observed: blurred
      vision and sedation. The BPRS decreased by 26.8 points after three days of
      treatment (p = 0.001). The BARS score, reflecting agitation, decreased
      significantly after each injection, reaching maximal decrease of 2.14 points at
      completion of study (p = 0.001). CONCLUSION: Intramuscular ziprasidone in this
      series of elderly patients suggests acceptable safety and efficacy in the
      management of acute psychotic agitation among elderly patients with
      schizophrenia.

PMID- 16816019
TI  - No associations of human pulmonary tuberculosis with Sp110 variants.
AB  - BACKGROUND: After a recent report on the role of the Ipr1 gene in mediating
      innate immunity in a mouse model of Mycobacterium tuberculosis infection, the
      human Ipr1 homologue, Sp110, was considered a promising candidate for an
      association study in human tuberculosis. METHODS: In a sample of >1000 sputum
      positive, HIV negative West African patients with pulmonary tuberculosis and
      >1000 exposed, apparently healthy controls, we have genotyped 21 Sp110 gene
      variants that were either available from public databases, including HapMap data,
      or identified by DNA re-sequencing. RESULTS: No significant differences in the
      frequencies of any of the 21 variants were observed between patients and
      controls. This applied also for HapMap tagging variants and the corresponding
      haplotypes, when including sliding window analyses with three adjacent variants,
      and when stratifying controls for positivity and negativity according to the
      results of intradermal tuberculin (purified protein derivative, PPD) skin tests.
      DNA re-sequencing revealed 13 novel Sp110 variants in the 5'-UTR, exons, and
      adjacent intronic regions. CONCLUSIONS: Based on the results obtained in this
      case-control study, the hypothesis that Sp110 variants and haplotypes might be
      associated with distinct phenotypes of human M tuberculosis infection is
      doubtful.

PMID- 16816020
TI  - AUNX1, a novel locus responsible for X linked recessive auditory and peripheral
      neuropathy, maps to Xq23-27.3.
AB  - BACKGROUND: We report here the genetic characterisation of a large five
      generation Chinese family with the phenotypic features of auditory neuropathy and
      progressive peripheral sensory neuropathy, and the genetic feature of X linked
      recessive inheritance. Disease onset was at adolescence (at an average age of 13
      years for six affected subjects). The degree of hearing impairment varied from
      mild to severe, with decreased otoacoustic emissions; auditory brainstem
      responses were lacking from onset. METHODS: Two-point and multipoint model based
      linkage analysis using the MILNK and LINKMAP programs of the FASTLINK software
      package produced maximum two-point and multipoint LOD scores of 2.41 and 2.41,
      respectively. RESULTS: These findings define a novel X linked auditory neuropathy
      locus/region (AUNX1, Xq23-q27.3). This region is 42.09 cM long and contains a
      28.07 Mb region with flanking markers DXS1220 and DXS8084, according to the
      Rutgers Combined Linkage-Physical Map, build 35. However, mutation screen of the
      candidate gene SLC6A14 within the region did not identify the causative genetic
      determinant for this large Chinese family.

PMID- 16816021
TI  - CHEK2 I157T associates with familial and sporadic colorectal cancer.
AB  - BACKGROUND: Recently, a functionally defective CHEK2 variant I157T has been
      proposed to associate with an increased risk of several types of cancer. We
      investigated the CHEK2 I157T variant for colorectal cancer (CRC) predisposition
      in a large population based study including a significant number of familial CRC
      cases. METHODS: We screened the CHEK2 I157T variant in a population based series
      of 1042 Finnish CRC patients using restriction fragment length polymorphism.
      Mutation status was studied for correlation with clinical characteristics and
      family history of CRC and other cancers. RESULTS: The frequency of CHEK2 I157T
      was significantly higher in CRC patients (7.8%, 76/972) than in healthy
      population controls (5.3%, 100/1885) (OR = 1.5, 95% CI 1.1 to 2.1, p = 0.008).
      The significant association of CHEK2 I157T with CRC was observed among patients
      with (10.4%, 14/135) and without (7.4%, 62/837) a family history of CRC (OR =
      2.1, 95% CI 1.1 to 3.7, p = 0.01; OR = 1.4, 95% CI 1.0 to 2.0, p = 0.03;
      respectively). A trend towards higher variant frequency was also noted among
      patients with multiple primary tumours and a family history of any cancer.
      CONCLUSIONS: CHEK2 I157T associates with an increased risk of CRC: the
      association was observed both among familial and sporadic CRC patients.
      Furthermore, the higher frequency of I157T among patients with multiple primary
      tumours as well as those with a family history of any cancer supports a role for
      CHEK2 I157T as a susceptibility allele for multiple cancer types.

PMID- 16816022
TI  - A novel susceptibility locus for Hirschsprung's disease maps to 4q31.3-q32.3.
AB  - We report on a multigenerational family with isolated Hirschsprung's disease
      (HSCR). Five patients were affected by either short segment or long segment HSCR.
      The family consists of two main branches: one with four patients (three siblings
      and one maternal uncle) and one with one patient. Analysis of the RET gene, the
      major gene involved in HSCR susceptibility, revealed neither linkage nor
      mutations. A genome wide linkage analysis was performed, revealing suggestive
      linkage to a region on 4q31-q32 with a maximum parametric multipoint LOD score of
      2.7. Furthermore, non-parametric linkage (NPL) analysis of the genome wide scan
      data revealed a NPL score of 2.54 (p = 0.003) for the same region on chromosome
      4q (D4S413-D4S3351). The minimum linkage interval spans a region of 11.7 cM (12.2
      Mb). No genes within this chromosomal interval have previously been implicated in
      HSCR. Considering the low penetrance of disease in this family, the 4q locus may
      be necessary but not sufficient to cause HSCR in the absence of modifying loci
      elsewhere in the genome. Our results suggest the existence of a new
      susceptibility locus for HSCR at 4q31.3-q32.3.

PMID- 16816023
TI  - Total absence of the alpha2(I) chain of collagen type I causes a rare form of
      Ehlers-Danlos syndrome with hypermobility and propensity to cardiac valvular
      problems.
AB  - BACKGROUND: Heterozygous mutations in the COL1A1 or COL1A2 gene encoding the
      alpha1 and alpha2 chain of type I collagen generally cause either osteogenesis
      imperfecta or the arthrochalasis form of Ehlers-Danlos syndrome (EDS). Homozygous
      or compound heterozygous COL1A2 mutations resulting in complete deficiency of the
      proalpha2(I) collagen chains are extremely rare and have been reported in only a
      few patients, albeit with variable phenotypic outcome. METHODS: The clinical
      features of the proband, a 6 year old boy, were recorded. Analysis of proalpha
      and alpha-collagen chains was performed by SDS-polyacrylamide gel electrophoresis
      using the Laemmli buffer system. Single stranded conformation polymorphism
      analysis of the proband's DNA was also carried out. RESULTS: In this report we
      show that complete lack of proalpha2(I) collagen chains can present as a
      phenotype reminiscent of mild hypermobility EDS during childhood. CONCLUSIONS:
      Biochemical analysis of collagens extracted from skin fibroblasts is a powerful
      tool to detect the subset of patients with complete absence of proalpha2(I)
      collagen chains, and in these patients, careful cardiac follow up with
      ultrasonography is highly recommended because of the risk for cardiac valvular
      problems in adulthood.

PMID- 16816024
TI  - A nonsense mutation in the first transmembrane domain of connexin 43 underlies
      autosomal recessive oculodentodigital syndrome.
AB  - BACKGROUND: Oculodentodigital syndrome (ODD) is a pleiotropic congenital disorder
      characterised by abnormalities of the face, eyes, dentition, and limbs. ODD,
      which is inherited as an autosomal dominant trait, results from missense
      mutations in the gap junction protein connexin 43. OBJECTIVE: To analyse a family
      with a history of ODD which is inherited in an autosomal recessive manner
      RESULTS: ODD in this family resulted from the homozygous mutation R33X in the
      first transmembrane domain of connexin 43. CONCLUSIONS: The findings provide
      clear genetic evidence that ODD can be inherited in an autosomal recessive manner
      and that a dominant negative mechanism underlies autosomal dominant ODD.

PMID- 16816025
TI  - The 13042G --> A/ND5 mutation in mtDNA is pathogenic and can be associated also
      with a prevalent ocular phenotype.
AB  - BACKGROUND: Overlapping phenotypes including LHON, MELAS, and Leigh syndrome have
      recently been associated with numerous mtDNA point mutations in the ND5 gene of
      complex I, now considered a mutational hot spot. OBJECTIVE: To identify the mtDNA
      defect in a family with a prevalent ocular phenotype, including LHON-like optic
      neuropathy, retinopathy, and cataract, but characterised also by strokes, early
      deaths, and miscarriages on the maternal line. RESULTS: Sequencing of the entire
      mitochondrial genome from the proband's muscle DNA identified the heteroplasmic
      13042G-->A transition, which was previously described only once in a patient with
      a different mitochondrial disease. This mutation fulfils the major pathogenic
      criteria, inducing an amino acid change (A236T) at an invariant position in a
      highly conserved domain of the ND5 gene. Phosphorus magnetic resonance
      spectroscopy in the proband disclosed an in vivo brain and skeletal muscle energy
      metabolism deficit. CONCLUSIONS: These findings conclusively establish the
      pathogenic role of the 13042G-->A mutation and underscore its variable clinical
      expression.

PMID- 16816026
TI  - Have the focus and sophistication of research in health education changed?
AB  - This study assessed the types of research and the statistical methods used in
      three representative health education journals from 1994 through 2003.
      Editorials, commentaries, program/practice notes, and perspectives represent
      17.6% of the journals' content. The most common types of articles are cross
      sectional studies (27.5%), reviews (23.2%), and analytic studies (i.e., case
      control, cohort, and experimental studies) (18.4%). The estimated annual
      percentage change across the study period in these types of articles was 3.3, 
      9.3, and 5.5, respectively. A significant increase was observed in use of
      descriptive statistics (estimated annual percentage change = 2.4), parametric
      test statistics (4.4), nonparametric test statistics (3.5), epidemiologic
      statistics (10.3), generalized linear models (6.8), validation statistics (6.7),
      and other statistics (8.2). Movement toward increasing use of cross-sectional
      studies, analytic study designs, and statistical methods--representing greater
      emphasis on needs assessment for health education, health education program
      development, and program evaluation--indicates the need for better quantitatively
      trained health educators.

PMID- 16816027
TI  - Syringe disposal among injection drug users in Harlem and the Bronx during the
      New York State Expanded Syringe Access Demonstration Program.
AB  - Effective January 1, 2001, New York State enacted the Expanded Syringe Access
      Demonstration Program (ESAP), allowing syringes to be sold in pharmacies without
      a prescription or dispensed through doctors, hospitals, and clinics to adults. A
      concern in the assessment of ESAP is its effects on syringe disposal practices.
      Syringe use data regarding the last injection episode were combined from three
      projects (N = 1,030) recruiting injection drug users. Disposal of syringes by
      methods known to be safe decreased significantly over time after the
      implementation of ESAP. Syringes obtained either from syringe exchange programs
      or ESAP sources were more likely to be disposed of safely than syringes obtained
      from other sources. Efforts to enlist pharmacists and others involved in ESAP
      implementation to encourage safe disposal are needed. More detailed information
      on disposal practices is needed to capture the continuum from least to most safe
      practices and variation within individuals.

PMID- 16816028
TI  - Measurement of behavioral objectives for weight management.
AB  - Measurement of specific behaviors involved in weight management is essential to
      understanding the behavior change process. This study presents measures of common
      behavioral objectives for weight management interventions. The relationships
      between these measures and conventional outcomes of weight management are
      described. Data are from a survey of 407 adults in the rural Midwest ages 23 to
      88. Analyses involved bivariate and multivariate statistical tests. Relationships
      were stronger when limited to diet or physical activity outcomes as opposed to
      body mass index or waist circumference. Diet-related strategies were more
      strongly correlated with diet-related outcomes than physical activity-related
      outcomes and vice versa. Measures of social interactions and self-monitoring for
      both diet and physical activity were consistently related to outcomes. The
      measures show promise as reliable and valid indicators of behavior that could be
      useful in the evaluation of interventions. Intervention studies are needed to
      further characterize their value and sensitivity to change over time.

PMID- 16816029
TI  - Design of a health-promoting neighborhood intervention.
AB  - Design and implementation of health-promoting community interventions can advance
      public health and community well-being; however, realization of such programs is
      often challenging. Even more challenging is the implementation of ecologic
      interventions to revitalize built urban environments. A structured intervention
      entitled ;Intersection Repair; was devised in Portland, Oregon, by a non-profit
      organization, to implement urban gathering places in the public right of way;
      specific steps included situation analysis, community outreach, asset mapping,
      design workshops, construction permitting, building workshops, and process
      evaluation. The community created human-scale urban landscapes with interactive
      art installations to encourage social interactions. Such aesthetic improvements,
      which included painted street murals, information kiosks, hanging gardens, water
      fountains, benches, and so on, were intended to strengthen social networks and
      social capital by providing places for residents to engage in conversation.
      Community engagement in neighborhood design benefits the public at multiple
      levels, by promoting a healthier lifestyle, over and above urban landscape
      improvements.

PMID- 16816030
TI  - Web-based tailored lifestyle programs: exploration of the target group's
      interests and implications for practice.
AB  - An important challenge in Web-based health promotion is to increase the reach of
      the target audience by taking the target groups' desires into consideration. Data
      from 505 members of a Dutch Internet panel (representative for Dutch Internet
      users) were used to asses the target group's interests and needs. 28%
      participated in Web-based tailored lifestyle programs, 57% expressed an interest
      in such programs, and 15% expressed no interest. Interest in Web-based programs
      was predominantly caused by a general interest in lifestyle and online tests.
      Participation in Web-based tailored lifestyle programs should not take more than
      17 minutes per occasion. 84% were interested in follow-up testing after the
      initial participation. Responders were particularly interested in physical
      activity and nutrition. Hardly anyone was willing to pay for participation. The
      results from this study support the use of Web-based tailored lifestyle programs
      in behavior change efforts.

PMID- 16816031
TI  - Promoting health and innovative health promotion practice through a community
      arts centre.
AB  - The salubrious effects of participation in and exposure to the arts are well
      documented. This paper describes the development of a unique arts centre
      established in a disadvantaged urban school setting as part of a larger community
      based health promotion research project. The discussion highlights how community
      based arts programming may impact health not only through positive effects on
      "upstream" non-medical health determinants, particularly aspects of social
      support, but also through its ability to facilitate the more traditional health
      promotion initiatives of the larger parent project. Also discussed is this
      centre's potential to act as a catalyst to achieve the overarching project goal
      of enhanced community health by building constitutive capacity around positive
      aspects of the community, rather than focusing on capacity only as an
      instrumental resource to solve social or health problems. Greater incorporation
      of the arts within health-promotion projects offers potential to enhance both
      health promotion practice and outcomes.

PMID- 16816032
TI  - If you build it, they will come: lessons from developing walking trails in rural
      Missouri.
AB  - Given the high rates of sedentary behaviors, attempts to increase physical
      activity have incorporated individual and, more recently, policy and
      environmental approaches for promotion of activity. This article presents a
      summary of the approaches being used by the Ozark Heart Health Coalitions in
      developing walking trails in rural Missouri. In summarizing these approaches the
      authors describe 10 lessons with the aim of articulating the process and,
      thereby, increasing interest and capacity in development of walking trails.
      Qualitative and quantitative data were used to show burden and priorities and
      build support with numerous stakeholders. Stakeholders were engaged to identify
      common objectives, obtain land and funding, and determine trail size, materials,
      and time needed for construction. Implementation activities focused on trail
      maintenance and addition of amenities (e.g., playgrounds, benches). In the area
      of evaluation, they collect data via interviews with walkers on trails and
      community telephone surveys.

PMID- 16816033
TI  - Promoting healthy people 2010 through small grants.
AB  - The Department of Health and Human Services initiated a pilot "microgrant" or
      small grants program in 2001 to promote Healthy People 2010 (HP 2010) implemented
      by the Yale-Griffin Prevention Research Center. This article describes the 103
      agencies funded under this initiative and 67 control group agencies. It evaluates
      the HP 2010 focus areas targeted and the effectiveness of promoting HP 2010
      objectives through microgrants. Forty-four percent of the grant recipients and
      79% of the control group agencies indicated low levels of familiarity with HP
      2010 goals. Changes in knowledge of HP 2010 goals for the microgrant group
      increased significantly from 5.24 +/- 3.67 to 7.83 +/- 1.86 (p < .05). The
      results suggest that microgrants can be a useful mechanism to plant the seeds for
      developing community and organizational capacity to define local health
      priorities, practice and test new initiatives or expand existing programs and
      promote knowledge about HP 2010.

PMID- 16816034
TI  - Wickedness or folly? The ethics of NICE's decisions.
AB  - A rebuttal is provided to each of the arguments adduced by John Harris, an Editor
      in-Chief of the Journal of Medical Ethics, in two editorials in the journal in
      support of the view that National Institute for Health and Clinical Excellence's
      procedures and methods for making recommendations about healthcare procedures for
      use in the National Health Service in England and Wales are the product of
      "wickedness or folly or more likely both", "ethically illiterate as well as
      socially divisive", responsible for the "perversion of science as well as of
      morality" and are "contrary to basic morality and contrary to human rights".

PMID- 16816036
TI  - Clinical ethical dilemmas: convergent and divergent views of two scholarly
      communities.
AB  - OBJECTIVE: To survey members of the American Society for Bioethics and Humanities
      (ASBH; n = 327) and of the Society for Medical Decision Making (SMDM; n = 77) to
      elicit the similarities and differences in their reasoning about two clinical
      cases that involved ethical dilemmas. CASES: Case 1 was that of a patient
      refusing treatment that a surgeon thought would be beneficial. Case 2 dealt with
      end-of-life care. The argument was whether intensive treatment should be
      continued of an unconscious patient with multiorgan failure. METHOD: Four
      questions, with structured multiple alternatives, were asked about each case:
      identified core problems, needed additional information, appropriate next steps
      and who the decision maker should be. OBSERVATIONS AND RESULTS: Substantial
      similarities were noticed between the two groups in identifying the core
      problems, the information needed and the appropriate next steps. SMDM members
      gave more weight to outcomes and trade-offs and ASBH members had patient autonomy
      trump other considerations more strongly. In case 1, more than 60% of ASBH
      respondents identified the patient alone as the decision maker, whereas members
      of SMDM were almost evenly divided between having the patient as the solo
      decision maker or preferring a group of some sort as the decision maker, a
      significant difference (p<0.02). In case 2, both groups agreed that the question
      of discontinuing treatment should be discussed with the family and that the
      family alone should not be the decision maker. CONCLUSION: Despite distinctively
      different methods of case analysis and little communication between the two
      professional communities, many similarities were observed in the actual decisions
      they reached on the two clinical dilemmas.

PMID- 16816038
TI  - Can patients be sure they are fully informed when representatives of surgical
      equipment manufacturers attend their operations?
AB  - OBJECTIVE: To determine the practice in UK hospitals regarding the level of
      patient involvement and consent when representatives of commercial surgical
      device manufacturers attend and advise during operations. METHODS: An anonymous
      postal questionnaire was sent to the senior nurse in charge in all 236 UK
      gynaecology theatres in 2004. 79/236 (33%) replies were received. RESULTS:
      Operating departments were visited every 2 weeks on average by a representative
      of the surgical device manufacturer. Actual operations were attended every 10
      weeks, although there was much variation. 33/79 (42%) units consistently obtained
      patient consent for visits, usually orally, whereas 40/79 (51%) units did not.
      65/79 (82%) units had no guidelines for surgical device representative visits.
      91% of nurses in charge believed that there should be guidelines to protect both
      patients and staff. 6/79 (8%) units were preparing local guidelines at the time
      of the survey. CONCLUSIONS: Currently, patient safety, confidentiality and
      autonomy are being protected by a minority of NHS operating theatres when
      surgical device representatives attend surgery. National guidelines would
      hopefully ensure that fully informed patient consent is obtained and that
      representatives are fully trained and supervised.

PMID- 16816037
TI  - Who is willing to take the risk? Assessing the readiness for living liver
      donation in the general German population.
AB  - BACKGROUND: Shortage of donor organs is one of the major problems for liver
      transplant programmes. Living liver donation is a possible alternative, which
      could increase the amount of donor organs available in the short term. OBJECTIVE:
      To assess the attitude towards living organ donation in the general population to
      have an overview of the overall attitude within Germany. METHODS: A
      representative quota of people was evaluated by a mail questionnaire (n = 250).
      This questionnaire had 24 questions assessing the willingness to be a living
      liver donor for different potential recipients. Factors for and against living
      liver donation were assessed. RESULTS: Donating a part of the liver was almost as
      accepted as donating a kidney. The readiness to donate was highest when
      participants were asked to donate for children. In an urgent life-threatening
      situation the will to donate was especially high, whereas it was lower in the
      case of recipient substance misuse. More women than men expressed a higher
      disposition to donate for their children. Sex, religion, state of health and age
      of the donor, however, did not influence other questions on the readiness to
      consider living organ donation. The will for postmortem organ donation positively
      correlated with the will to be a living organ donor. CONCLUSIONS: The motivation
      in different demographic subgroups to participate in living liver transplantation
      is described. Differences in donation readiness resulting from the situation of
      every donor and recipient are thoroughly outlined. The acceptance for a living
      liver donation was found to be high - and comparable to that of living kidney
      donation.

PMID- 16816039
TI  - Privacy and patient-clergy access: perspectives of patients admitted to hospital.
AB  - BACKGROUND: For patients admitted to hospital both pastoral care and privacy or
      confidentiality are important. Rules related to each have come into conflict
      recently in the US. Federal laws and other rules protect confidentiality in ways
      that countermand hospitals' methods for facilitating access to pastoral care.
      This leads to conflicts and poses an unusual type of dilemma-one of conflicting
      values and rights. As interests are elements necessary for establishing rights,
      it is important to explore patients' interests in privacy compared with their
      desire for attention from a cleric. AIM: To assess the willingness of patients to
      have their names and rooms included on a list by religion, having that
      information given to clergy without their consent, their sense of privacy
      violation if that were done and their views about patients' privacy rights.
      METHODS AND PARTICIPANTS: 179 patients, aged 18-92 years, admitted to hospital in
      an acute care setting, were interviewed and asked about their preferences for
      confidentiality and pastoral support. RESULTS: Most (57%) patients did not want
      to be listed by religion; 58% did not think hospitals should give lists to clergy
      without their consent and 84% welcomed a visit by their own clergy even if
      triggered from a hospital list. CONCLUSIONS: Values related to confidentiality or
      privacy and pastoral care were found to be inconsistent and more complicated than
      expected. Balancing the right to privacy and the value of religious support
      continue to present a challenge for hospitals. Patients' preferences support the
      importance of providing balance in a way that protects rights while offering
      comprehensive services.

PMID- 16816040
TI  - (When) will they have faces? A response to Agich and Siemionov.

PMID- 16816041
TI  - Ethical issues in psychopharmacology.
AB  - The marketing of selective serotonin reuptake inhibitors in the
      psychopharmacological industry presents a serious moral problem for the corporate
      model of medicine. In this paper I examine ethical issues relating to the
      efficacy and safety of these drugs. Pharmaceutical companies have a moral
      obligation to disclose all information in their possession bearing on the true
      risks and benefits of their drugs. Only then can patients make fully informed
      decisions about their treatment.

PMID- 16816042
TI  - Rural and non-rural differences in membership of the American Society of
      Bioethics and Humanities.
AB  - OBJECTIVE: To determine whether bioethicists are distributed along a rural-to
      urban continuum in a way that reflects potential need of those resources as
      determined by the general population, hospital facilities and hospital beds.
      METHODS: US members of a large, multidisciplinary professional society, the
      American Society of Bioethics and Humanities (ASBH), the US population, hospital
      facilities and hospital beds were classified across a four-tier rural-to-urban
      continuum. The proportion of each group in rural settings was compared with that
      in urban settings, and odds ratios were calculated with 95% confidence intervals.
      RESULTS: Although 91% of ASBH members live or work in urban settings, only 66% of
      the US population did so. In contrast, 2% of ASBH members live or work in rural
      settings compared with 13% of the population. ASBH members were 10.7 times (95%
      CI 6.6 to 17.3) as likely to be represented in urban than in rural settings when
      compared with the general population, 25.6 times (95% CI 15.8 to 41.5) and 6.9
      times (95% CI 4.3 to 11.1) as likely with regard to hospital facilities and
      hospital beds, respectively. CONCLUSIONS: Using various comparisons it was found
      that ASBH members are under-represented in rural as compared with urban settings.
      Although not all bioethicists are ASBH members, these findings suggest that the
      availability of professional bioethical resources may be inadequate in rural
      America. The disparities that were found may have considerable effect on ethics
      scholarship, research, ethical committees and education, and adds to the argument
      that rural American communities are under-served.

PMID- 16816043
TI  - Do French lay people and health professionals find it acceptable to breach
      confidentiality to protect a patient's wife from a sexually transmitted disease?
AB  - OBJECTIVE: To determine under what conditions lay people and health professionals
      find it acceptable for a physician to breach confidentiality to protect the wife
      of a patient with a sexually transmitted disease (STD). METHODS: In a study in
      France, breaching confidentiality in 48 scenarios were accepted by 144 lay
      people, 10 psychologists and 7 physicians. The scenarios were all possible
      combinations of five factors: severity of the disease (severe, lethal); time
      taken to discuss this with (little time, much time); intent to inform the spouse
      about the disease (none, one of these days, immediately); intent to adopt
      protective behaviours (no intent, intent); and decision to consult an expert in
      STDs (yes, no), 2 x 2 x 3 x 2 x 2. The importance and interactions of each factor
      were determined, at the group level, by performing analyses of variance and
      constructing graphs. RESULTS: The concept of breaching confidentiality to protect
      a wife from her husband's STD was favoured much more by lay people and
      psychologists than by physicians (mean ratings 11.76, 9.28 and 2.90,
      respectively, on a scale of 0-22). The patient's stated intentions to protect his
      wife and to inform her of the disease had the greatest impact on acceptability. A
      cluster analysis showed groups of lay participants who found breaching
      confidentiality "always acceptable" (n = 14), "depending on the many
      circumstances" (n = 87), requiring "consultation with an expert" (n = 30) and
      "never acceptable (n = 13)". CONCLUSIONS: Most people in France are influenced by
      situational factors when deciding if a physician should breach confidentiality to
      protect the spouse of a patient infected with STD.

PMID- 16816044
TI  - Authorship of research papers: ethical and professional issues for short-term
      researchers.
AB  - Although the International Committee of Medical Journal Editors has published
      clear guidance on the authorship of scientific papers, short-term contract
      research workers, who perform much of the research that is reported in the
      biomedical literature, are often at a disadvantage in terms of recognition,
      reward and career progression. This article identifies several professional,
      ethical and operational issues associated with the assignment of authorship,
      describes how a university department of primary care set about identifying and
      responding to the concerns of its contract research staff on authorship and
      describes a set of guidelines that were produced to deal with the ethical and
      professional issues raised. These guidelines include directions on how authorship
      should be negotiated and allocated and how short-term researchers can begin to
      develop as authors. They also deal with the structures required to support an
      equitable system, which deals with the needs of short-term researchers in ways
      that are realistic in the increasingly competitive world of research funding and
      publication, and may offer a model for more formal guidelines that could form
      part of institutional research policy.

PMID- 16816045
TI  - Distinguishing treatment from research: a functional approach.
AB  - The best way to distinguish treatment from research is by their functions. This
      mode of distinction fits well with the basic ethical work that needs to be
      carried out. The distinction needs to serve as an ethical flag, highlighting
      areas in which the goals of doctors and patients are more likely than usual to
      diverge. The distinction also allows us to illuminate and understand some
      otherwise puzzling elements of debates on research ethics: it shows the
      peculiarity of exclusive conceptions of the distinction between research and
      treatment; it allows us to frame questions about therapeutic obligations in the
      research context, and it allows us to consider whether there may be research
      obligations in the therapeutic context.

PMID- 16816047
TI  - Cesarean birth: guidelines, not rules.

PMID- 16816046
TI  - Non-commercial clinical trials of a medicinal product: can they survive the
      current process of research approvals in the UK?
AB  - Over recent years, considerable attention has been paid to the National Health
      Service (NHS) research governance and ethics approvals process in the UK. New
      regulations mean that approval from the Medicines and Healthcare Products
      Regulatory Agency (MHRA) is now also needed for conducting all clinical trials.
      Practical experience of gaining MHRA and sponsorship approval has yet to be
      described and critically explored in the literature. Our experience, from start
      to finish, of applying for these four approvals for a multicentre randomised
      controlled trial of two licensed drugs for opiate detoxification in the prison
      setting is described here. In addition, the implications of the approvals process
      for research projects, particularly clinical trials, in terms of time and
      funding, and also indirect implications for NHS patients are discussed.
      Inconsistencies are discussed and suggestions that could improve and streamline
      the overall process are made. The current approvals process could now be
      hindering non-commercial clinical trials, leading to a loss of important evidence
      based medical information.

PMID- 16816048
TI  - Evolving approaches in the treatment of menopausal symptoms.

PMID- 16816049
TI  - Decision-to-incision times and maternal and infant outcomes.
AB  - OBJECTIVE: To measure decision-to-incision intervals and related maternal and
      neonatal outcomes in a cohort of women undergoing emergency cesarean deliveries
      at multiple university-based hospitals comprising the National Institute of Child
      Health and Human Development Maternal-Fetal Medicine Units Network. METHODS: All
      women undergoing a primary cesarean delivery at a Network center during a 2-year
      time span were prospectively ascertained. Emergency procedures were defined as
      those performed for umbilical cord prolapse, placental abruption, placenta previa
      with hemorrhage, nonreassuring fetal heart rate pattern, or uterine rupture.
      Detailed information regarding maternal and neonatal outcomes, including the
      interval from the decision time to perform cesarean delivery to the actual skin
      incision, was collected. RESULTS: Of the 11,481 primary cesarean deliveries,
      2,808 were performed for an emergency indication. Of these, 1,814 (65%) began
      within 30 minutes of the decision to operate. Maternal complication rates,
      including endometritis, wound infection, and operative injury, were not related
      to the decision-to-incision interval. Measures of newborn compromise including
      umbilical artery pH less than 7 and intubation in the delivery room were
      significantly greater when the cesarean delivery was commenced within 30 minutes,
      likely attesting to the need for expedited delivery. Of the infants with
      indications for an emergency cesarean delivery who were delivered more than 30
      minutes after the decision to operate, 95% did not experience a measure of
      newborn compromise. CONCLUSION: Approximately one third of primary cesarean
      deliveries performed for emergency indications are commenced more than 30 minutes
      after the decision to operate, and the majority were for nonreassuring heart rate
      tracings. In these cases, adverse neonatal outcomes were not increased. LEVEL OF
      EVIDENCE: II-2.

PMID- 16816050
TI  - Risk of uterine rupture with a trial of labor in women with multiple and single
      prior cesarean delivery.
AB  - OBJECTIVE: To determine whether the risk for uterine rupture is increased in
      women attempting vaginal birth after multiple cesarean deliveries. METHODS: We
      conducted a prospective multicenter observational study of women with prior
      cesarean delivery undergoing trial of labor and elective repeat operation.
      Maternal and perinatal outcomes were compared among women attempting vaginal
      birth after multiple cesarean deliveries and those with a single prior cesarean
      delivery. We also compared outcomes for women with multiple prior cesarean
      deliveries undergoing trial of labor with those electing repeat cesarean
      delivery. RESULTS: Uterine rupture occurred in 9 of 975 (0.9%) women with
      multiple prior cesarean compared with 115 of 16,915 (0.7%) women with a single
      prior operation (P = .37). Multivariable analysis confirmed that multiple prior
      cesarean delivery was not associated with an increased risk for uterine rupture.
      The rates of hysterectomy (0.6% versus 0.2%, P = .023) and transfusion (3.2%
      versus 1.6%, P < .001) were increased in women with multiple prior cesarean
      deliveries compared with women with a single prior cesarean delivery attempting
      trial of labor. Similarly, a composite of maternal morbidity was increased in
      women with multiple prior cesarean deliveries undergoing trial of labor compared
      with those having elective repeat cesarean delivery (odds ratio 1.41, 95%
      confidence interval 1.02-1.93). CONCLUSION: A history of multiple cesarean
      deliveries is not associated with an increased rate of uterine rupture in women
      attempting vaginal birth compared with those with a single prior operation.
      Maternal morbidity is increased with trial of labor after multiple cesarean
      deliveries, compared with elective repeat cesarean delivery, but the absolute
      risk for complications is small. Vaginal birth after multiple cesarean deliveries
      should remain an option for eligible women. LEVEL OF EVIDENCE: II-2.

PMID- 16816051
TI  - Maternal complications associated with multiple cesarean deliveries.
AB  - OBJECTIVE: The claim that a planned repeat cesarean delivery is safer than a
      trial of labor after cesarean may not be applicable to women who desire larger
      families. The aim of this study was to assess maternal complications after
      multiple cesarean deliveries. METHODS: The records of women who underwent two or
      more planned cesarean deliveries between 2000 and 2005 were reviewed. We compared
      maternal complications occurring in 277 women after three or more cesarean
      deliveries (multiple-cesarean group) with those occurring in 491 women after
      second cesarean delivery (second-cesarean group). RESULTS: Excessive blood loss
      (7.9% versus 3.3%; P < .005), difficult delivery of the neonate (5.1% versus
      0.2%; P < .001), and dense adhesions (46.1% versus 25.6%; P < .001) were
      significantly more common in the multiple-cesarean group. Placenta accreta (1.4%)
      and hysterectomy (1.1%) were more common, but not significantly so, in the
      multiple-cesarean group. The proportion of women having any major complication
      was higher in the multiple-cesarean group, 8.7% versus 4.3% (P = .013), and
      increased with the delivery index number: 4.3%, 7.5%, and 12.5% for second,
      third, and fourth or more cesarean delivery, respectively (P for trend = .004).
      CONCLUSION: Multiple cesarean deliveries are associated with more difficult
      surgery and increased blood loss compared with a second planned cesarean
      delivery. The risk of major complications increases with cesarean delivery
      number. LEVEL OF EVIDENCE: II-2.

PMID- 16816052
TI  - Algorithm for treatment of postoperative incisional groin pain after cesarean
      delivery or hysterectomy.
AB  - OBJECTIVE: Despite the low mortality and morbidity of major obstetric and
      gynecologic surgeries (including hysterectomy and cesarean delivery), women
      undergoing these procedures occasionally suffer from intractable postoperative
      suprapubic and groin pain. We present seven patients whose intractable pain
      lasted longer than 6 months and was not due to gynecologic disease or other
      obvious pathology. METHODS: Neuromas of the ilioinguinal, iliohypogastric, and/or
      genitofemoral nerves were suspected clinically and confirmed intraoperatively.
      RESULTS: After neuroma resection, all patients reported complete and durable pain
      relief. CONCLUSION: Intractable pain after obstetric or gynecologic surgery can
      be due to neuroma formation, and resection is therapeutic. We suggest an
      algorithm for the management of women with chronic intractable suprapubic or
      groin pain after major obstetric and gynecologic surgery. LEVEL OF EVIDENCE: II
      3.

PMID- 16816053
TI  - Changes in U.S. prescribing patterns of menopausal hormone therapy, 2001-2003.
AB  - OBJECTIVE: In 2002, the combination estrogen-progestin hormone therapy (HT)
      treatment arm of the Women's Health Initiative was terminated early because
      cardiovascular and cancer risks were identified, while the estrogen-only therapy
      (ET) arm of this trial continued. We investigated hormone therapy prescription
      practice changes between 2001 and 2003 to explore the effects of the clinical
      trial results. METHODS: Data were obtained from the National Ambulatory Medical
      Care Survey and the National Hospital Ambulatory Medical Care Survey for the
      years 2001 through 2003. These nationally representative surveys sample medical
      encounters in nonfederally employed physician's offices and outpatient
      departments of nonfederal short-stay and general hospitals. The proportion and
      rate of visits with ET and HT prescriptions were calculated. Logistic regression
      was used to estimate change over time accounting for patient and provider
      characteristics. RESULTS: Between 2001 and 2003, the number of visits with
      menopausal hormone prescriptions fell from 26.5 million to 16.9 million. Almost
      three-quarters of hormone visits were for ET prescriptions. The decrease in the
      rate of visits was slightly larger for HT prescription visits (44%) than ET
      prescription visits (35%). The rate of decline was highest among women 50 years
      of age and over. After controlling for covariates, there was no significant
      difference in the decline by hormone type. CONCLUSION: These nationally
      representative data indicate substantial declines in menopausal hormone
      prescriptions coinciding with clinical trial results on HT. These declines
      occurred among all types of therapy and patient characteristics. LEVEL OF
      EVIDENCE: II-3.

PMID- 16816054
TI  - Gabapentin, estrogen, and placebo for treating hot flushes: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare the efficacy of gabapentin, estrogen, and placebo in the
      treatment of hot flushes. METHODS: We performed a randomized, double-blind,
      placebo-controlled trial of 60 postmenopausal women to assess the efficacy of
      estrogen and gabapentin in the treatment of moderate-to-severe hot flushes.
      Participants were randomly assigned to receive either 0.625 mg/d of conjugated
      estrogens (n = 20), placebo (n = 20), or gabapentin titrated to 2,400 mg/d (n =
      20) for 12 weeks. Participants recorded frequency and severity of baseline hot
      flushes on a hot flush diary for 2 weeks before randomization and for 12 weeks
      after randomization. The primary outcome measure was the weekly hot flush
      composite score, which takes into account both severity and frequency of hot
      flushes. Secondary outcome measures were differences in pre- and posttreatment
      scores pertaining to depression (Zung Depression Scale) and other climacteric
      symptoms (Greene Climacteric Scale). RESULTS: Intention-to-treat analysis showed
      that the reduction in the hot flush composite score for both estrogen (72%, P =
      .016) and gabapentin (71%, P = .004) was greater than the reduction associated
      with placebo (54%) at the conclusion of the 12th week. The extent of reduction in
      hot flush composite score, however, was not significantly different between
      estrogen and gabapentin (P = .63). No differences were seen between groups in the
      Zung Depression Scale, or in any of the Greene Climacteric subscales except for
      the Somatic Symptom cluster, which was significantly greater in the gabapentin
      arm than in the placebo arm. Despite a lack of group differences in adverse
      events, the Headache, Dizziness, and Disorientation cluster appeared with greater
      frequency in the gabapentin group. Estimation of the number needed to harm in
      this cluster suggests that these symptoms may occur with every fourth patient
      treated with gabapentin. CONCLUSION: Despite the small scale of this study,
      gabapentin appears to be as effective as estrogen in the treatment of
      postmenopausal hot flushes. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT
      00276081. LEVEL OF EVIDENCE: I.

PMID- 16816055
TI  - Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery
      for uterine leiomyomata.
AB  - OBJECTIVE: Magnetic-resonance-guided focused ultrasound is a novel, noninvasive
      technique of thermoablation for uterine leiomyomata. The hypothesis of this study
      was that pretreatment of leiomyomata with gonadotrophin-releasing hormone (GnRH)
      agonists would allow effective treatment of larger uterine leiomyomata,
      increasing the number of women who could benefit from this technique. METHODS: We
      report a prospective study of women with leiomyomata in excess of 10 cm in
      diameter who received GnRH agonist before magnetic-resonance-guided focused
      ultrasound treatment. Eligible participants were recruited from the gynecology
      outpatient clinics. Entry criteria were a minimal leiomyoma symptom severity
      score and confirmation of uterine dimensions based on screening magnetic
      resonance imaging. These women received a 3-month course of GnRH agonists
      followed by magnetic-resonance-guided focused ultrasound treatment. The primary
      outcome measurement was reported change in symptom severity score as judged by
      the Uterine Fibroid Symptom and Quality of Life questionnaire. Comparison was
      made at enrollment, treatment, and at 3, 6, and 12 months posttreatment. A
      secondary outcome was the measured change in target leiomyoma volume. RESULTS:
      Forty-nine women were enrolled in the study. There was a 45% reduction in median
      symptom severity score at 6 months and 48% at 12 months posttreatment, with 83%
      of women achieving at least a 10-point reduction in symptom scoring at 6 months
      and 89% at 12 months (P < .001). There was an average reduction in target
      leiomyoma volume of 21% overall at 6 months (P < .001) and 37% at 12 months (P <
      .001). No serious infective complications or emergency operative interventions
      were recorded. CONCLUSION: The use of GnRH agonist therapy before magnetic
      resonance-guided focused ultrasound improves the thermoablative treatment effect.
      LEVEL OF EVIDENCE: II-3.

PMID- 16816056
TI  - Defibulation to treat female genital cutting: effect on symptoms and sexual
      function.
AB  - OBJECTIVE: Women who have undergone type III female genital cutting may suffer
      long-term complications. Defibulation (reconstructive surgery of the infibulated
      scar) can alleviate some of these complications. We studied the physical and
      sexual outcomes after defibulation and evaluated both patient and husband
      satisfaction. METHODS: The medical records of 40 consecutive women with a history
      of type III female genital cutting who underwent defibulation between 1995 and
      2003 were reviewed. Data collected included demographics, indications for the
      procedure, closure type, intraoperative and postoperative complications.
      Telephone surveys were conducted between 6 months and 2 years postprocedure to
      evaluate the long-term health and sexual satisfaction outcomes. RESULTS: Of 40
      women identified as having undergone defibulation, 95% were Somali, 65% were
      married, and 73% were between the ages of 19 and 30. Primary indications for
      defibulation were being pregnant (30%), dysmenorrhea (30%), apareunia (20%), and
      dyspareunia (15%). Secondary indications were apareunia (20%), difficulty
      urinating (12.5%), and dyspareunia (10%). Sixty-five percent had a subcuticular
      repair. Forty-eight percent had an intact clitoris buried beneath the scar. None
      had intraoperative or postoperative complications. Of the 32 patients reached by
      telephone, 94% stated they would highly recommend it to others. One hundred
      percent of patients and their husbands were satisfied with the results, felt
      their appearance had improved, and were sexually satisfied. CONCLUSION:
      Defibulation is recommended for all infibulated women who suffer long-term
      complications. The complication rates are minimal, with high satisfaction rates
      among patients and their husbands. LEVEL OF EVIDENCE: II-3.

PMID- 16816057
TI  - Obstetric outcomes after in vitro fertilization in obese and morbidly obese
      women.
AB  - OBJECTIVE: In addition to numerous health detriments caused by obesity, fertility
      and pregnancy success may also be compromised. The aims of this study were to
      compare the effects of obesity and morbid obesity on in vitro fertilization (IVF)
      outcomes. We also investigated the effects of obesity on obstetric outcomes after
      IVF treatment. METHODS: Retrospective study of women less than 38 years of age
      during their first fresh IVF cycle (January 1995 to April 2005). RESULTS: A total
      of 1,293 women were included in the study, with 236 obese women (body mass index
      [BMI] = 30-39.9) and 79 morbidly obese women (BMI > or = 40). The morbidly obese
      group had a 25.3% IVF cycle cancellation rate compared with 10.9% in normal
      weight women (odds ratio 2.73, 95% confidence interval 1.49-5.0), P < .001).
      Morbidly obese women without polycystic ovarian syndrome had an even higher
      cancellation rate (33%). Women with higher BMI required significantly more days
      of gonadotropin stimulation but had lower peak estradiol levels (P < .001). There
      were no significant differences in clinical pregnancy or delivery rates between
      the four BMI groups. Of the women who delivered, there was a significant linear
      trend for risk of preeclampsia, gestational diabetes, and cesarean delivery with
      increasing BMI (P < .03). CONCLUSION: We report a significantly higher risk for
      IVF cycle cancellation in morbidly obese patients with no effect of BMI on
      clinical pregnancy or delivery rate. However, obese and morbidly obese subjects
      had a significantly higher risk for obstetric complications. This target
      population should be aggressively counseled regarding their increased obstetric
      risk and offered treatment options for weight reduction before the initiation of
      fertility therapy. LEVEL OF EVIDENCE: II-2.

PMID- 16816058
TI  - Fear of childbirth and pregnancy-related anxiety in women conceiving with
      assisted reproduction.
AB  - OBJECTIVE: To compare the prevalence and predictors of severe fear of childbirth
      and pregnancy-related anxiety in groups of assisted reproduction treatment (ART)
      and spontaneously conceiving women with singleton pregnancies. METHODS: The ART
      group (n = 367, nulliparous 260) represented a cohort from five Finnish
      infertility clinics in 1999. The control group (n = 379, nulliparous 135) was
      enrolled in this study by consecutive sampling the same year. Fear of childbirth
      was assessed by means of the revised version of the Fear-of-Childbirth
      Questionnaire and pregnancy-related anxiety by means of the Pregnancy Anxiety
      Scale at gestational week 20 +/- 3.2 (mean+/-standard deviation). RESULTS: The
      frequency of severe fear of childbirth and anxiety (classified as total scores in
      the 90th percentile or higher in the revised Fear of Childbirth Questionnaire and
      Pregnancy Anxiety Scale) did not differ between the groups. Nulliparity was
      associated with more frequent severe anxiety only in the controls. In nulliparous
      participants, a partnership of more than 5 years decreased the risk of severe
      fear of childbirth (odds ratio 0.3, 95% confidence interval 0.2-0.7). In the
      nulliparous ART group, a long duration of infertility (7 or more years) increased
      the risk of severe fear of childbirth (odds ratio 4.4, 95% confidence interval
      1.2-16.9). CONCLUSION: Women conceiving after ART do not experience severe fear
      of childbirth or pregnancy-related axiety more often than spontaneously
      conceiving controls. However, a long duration of infertility is an independent
      risk factor regarding severe fear of childbirth. LEVEL OF EVIDENCE: II-2.

PMID- 16816059
TI  - Association of obesity with pulmonary and nonpulmonary complications of pregnancy
      in asthmatic women.
AB  - OBJECTIVE: To evaluate whether maternal obesity is associated with pulmonary and
      nonpulmonary pregnancy complications in asthmatic women. METHODS: This is a
      secondary analysis of the prospective cohort Asthma During Pregnancy Study.
      Asthma patients were classified as having either mild or moderate to severe
      disease at the beginning of the study. Rates of pulmonary complications of asthma
      in asthmatic women and rates of nonpulmonary complications of pregnancy among
      asthma patients and controls, were compared between obese (body mass index > or =
      30 kg/m2) and nonobese women. RESULTS: Maternal body mass index and pregnancy
      outcome data were available for 1,699 of 1,812 asthmatic women and for 867 of 881
      controls. Of the asthma subjects, 30.7% (521) were obese compared with 25.5% of
      the controls, P = .006. Obese women, regardless of whether they had asthma, were
      more likely to undergo cesarean delivery (OR 1.6, 95% confidence interval [CI]1.3
      2.0) to develop preeclampsia or gestational hypertension (OR 1.7 95% CI 1.3-2.3)
      and gestational diabetes (OR 4.2, 95% CI 2.8-6.3). There were no differences in
      the rates of overall asthma improvement (20.6% compared with 23.6%, P = .36) or
      deterioration (33.3% compared with 28.8%, P = .20) between obese and nonobese
      asthma patients. After adjustment for confounding variables, obesity, not asthma,
      was associated with nonpulmonary complications of pregnancy, and obesity was
      associated with an increase in asthma exacerbations as well (OR 1.3, 95% CI 1.1
      1.7). CONCLUSION: Obesity is associated with an increased risk of asthma
      exacerbations during pregnancy. The increased rate of nonpulmonary complications
      of pregnancy in asthma patients is associated with obesity in this population and
      not with asthma status. LEVEL OF EVIDENCE: II-1.

PMID- 16816060
TI  - Efficacy of telephone counseling for pregnant smokers: a randomized controlled
      trial.
AB  - OBJECTIVE: Reducing tobacco use in pregnancy is a public health priority. Brief
      smoking counseling during prenatal care is effective but generates modest
      cessation rates. Telephone counseling is an effective smoking cessation method
      that could offer pregnant women convenient access to more intensive smoking
      cessation counseling. METHODS: The efficacy of proactive pregnancy-tailored
      telephone counseling for smoking cessation was compared with a "best-practice"
      brief-counseling control in a randomized controlled trial of 442 pregnant smokers
      referred by prenatal providers and a managed care plan. Trained counselors using
      cognitive-behavioral and motivational interviewing methods called intervention
      subjects throughout pregnancy and for 2 months postpartum (mean = 5 calls, mean
      total contact = 68 minutes). Controls received one 5-minute counseling call.
      RESULTS: Cotinine-validated 7-day tobacco abstinence rates in intervention and
      control groups were 10.0% and 7.5% at end of pregnancy (odds ratio [OR] 1.37, 95%
      confidence interval [CI] 0.69-2.70; number needed to treat = 40) and 6.7% versus
      7.1% at 3 months postpartum (OR 0.93, 95% CI 0.44-1.99). The intervention
      increased end-of-pregnancy cessation rates among 201 light smokers (< 10
      cigarettes/day at study enrollment) (intervention 19.1% versus control 8.4%; OR
      2.58, 95% CI 1.1-6.1; number needed to treat = 9.3) and among 193 smokers who
      attempted to quit in pregnancy before enrollment (intervention 18.1% versus
      control 6.8%; OR 3.02, CI 1.15-7.94; number needed to treat = 8.8); 63% of the
      sample (n = 267) was in one of these subgroups. CONCLUSION: Proactive pregnancy
      tailored telephone counseling did not outperform a brief "best practice"
      intervention among pregnant smokers. The intervention had efficacy in light
      smokers and in women who had attempted cessation earlier in pregnancy. Future
      studies should confirm whether telephone counseling benefits these groups of
      pregnant smokers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, #NCT00181909.
      LEVEL OF EVIDENCE: I.

PMID- 16816061
TI  - Effect of vaginal pessaries on symptoms associated with pelvic organ prolapse.
AB  - OBJECTIVE: To prospectively evaluate the effects of vaginal pessaries on symptoms
      associated with pelvic organ prolapse and identify the risk factors for failure.
      METHODS: All women referred to a specialist urogynecology unit with symptomatic
      pelvic organ prolapse who elected to use a pessary were included in this study.
      All completed the Sheffield pelvic organ prolapse symptom questionnaire before
      use and after 4 months of use. The primary outcome measure was change of symptoms
      from baseline to 4 months. RESULTS: Of 203 consecutive women fitted with a
      pessary, 153 (75%) successfully retained the pessary at 2 weeks, and 97 completed
      the questionnaires at 4 months. Multivariate logistic regression analysis showed
      that failure to retain the pessary was significantly associated with increasing
      parity (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.14-2.02, P = .004)
      and hysterectomy (OR 4.57, 95% CI 1.71-12.25, P = .002). In the success group at
      4 months (n = 97), a significant improvement in voiding was reported by 39
      participants (40%, P = .001), in urinary urgency by 37 (38%, P = .001), in urge
      urinary incontinence by 28 (29%, P = .015), in bowel evacuation by 27 (28%, P =
      .045), in fecal urgency by 22 (23%, P = .018), and in urge fecal incontinence by
      19 (20%, P = .027), but there was no significant improvement in stress urinary
      incontinence in 22 participants (23% P = .275). Of the 26 (27%) who were sexually
      active, 16 (17%, P = .001) reported an increase in frequency of sexual activity,
      and 11 (11%, P = .041) had improved in sexual satisfaction. CONCLUSION: A vaginal
      pessary is an effective and simple method of alleviating symptoms of pelvic organ
      prolapse and associated pelvic floor dysfunction. Failure to retain the pessary
      is associated with increasing parity and previous hysterectomy. LEVEL OF
      EVIDENCE: II-3.

PMID- 16816062
TI  - Adnexal torsion involving hydatids of Morgagni: a rare cause of acute abdominal
      pain in adolescents.
AB  - OBJECTIVE: Hydatids of Morgagni are common embryonal remnants of the mullerian
      duct and among the infrequent causes of adnexal torsion. The purpose of this
      study was to investigate the occurrence of adnexal torsion involving hydatids of
      Morgagni, as well as its possible mechanisms. METHODS: A database search was
      conducted for cases of adnexal torsion treated in our institution from January
      2002 to July 2005. These cases were analyzed, focusing on a subgroup of
      adolescents with adnexal torsion involving the hydatids of Morgagni. RESULTS:
      There were 76 patients with adnexal torsion. The rate of hydatid of Morgagni
      torsion was 26% (4 of 15 cases, 95% confidence interval [CI] 0.15-0.51) in the
      adolescent subgroup (10-19 years old), compared with 0% (0 of 61 cases, 95% CI 0
      0.048) in the adult subgroup. The difference between the hydatid torsion rates in
      the two subgroups was statistically significant (P = .01, 95% CI 0.001-0.532).
      The four patients with hydatid torsion (postmenarchal girls, aged 13-18 years)
      were managed with laparoscopic adnexal detorsion and cystectomy of the affected
      hydatid of Morgagni. At surgery, we noted three different mechanisms of hydatid
      torsion: torsion of the adnexa together with torsion of the hydatid of Morgagni,
      torsion of the hydatid of Morgagni with intact adnexa (n = 2), and entanglement
      of the hydatid's pedicle around the distal fallopian tube. The hydatids of
      Morgagni were observed on the preoperative transabdominal ultrasonogram in only
      one patient and appeared as a simple cyst. CONCLUSION: Adnexal torsion involving
      the hydatids of Morgagni appears to be more common in adolescents than previously
      thought. LEVEL OF EVIDENCE: III.

PMID- 16816063
TI  - Patient preferences, satisfaction, and resource use in office evacuation of early
      pregnancy failure.
AB  - OBJECTIVE: To examine patient treatment preferences and satisfaction with an
      office-based procedure for early pregnancy failure and to compare resource use
      and cost between office and operating room management of early pregnancy failure.
      METHODS: This study was a prospective observational study of 165 women presenting
      for surgical management of early pregnancy failure. Participants completed a
      preoperative questionnaire addressing treatment preferences and expectations and
      a postoperative questionnaire measuring level of pain experienced and
      satisfaction with care. Resource use was determined by measuring the time
      patients spent at the health care facility and the actual procedure time. Cost
      was estimated using an institutional database. RESULTS: One hundred fifteen women
      from the office and 50 from the operating room were enrolled. Patients selecting
      outpatient management scored "privacy," "avoiding going to sleep," and "previous
      experience" higher than the operating room group (P < .05). Patients who
      perceived that their physicians preferred one procedure over the other were more
      likely to select that procedure (P < .001). Satisfaction was high in both groups,
      and underestimating the procedure's discomfort was negatively associated with
      satisfaction (P < .002). Costs were greater than two-fold higher in the operating
      room group compared with the office group (P < .01). Complications were uncommon,
      but hemorrhage-related complications were four times more common in the operating
      room group than in the office group (P < .01). CONCLUSION: Office-based surgical
      management of early pregnancy failure is an acceptable option for many women and
      offers substantial resource and cost savings. LEVEL OF EVIDENCE: II-2.

PMID- 16816064
TI  - Reproductive health, criminal activity, and abuse among 10- to 15-year-old
      females enrolled in medicaid.
AB  - OBJECTIVE: To quantify the degree of abuse or criminal behavior among young
      females presenting for reproductive health care services. METHODS: An evaluation
      was conducted among Alaskan females age 10 through 15 years enrolled in Medicaid.
      Subjects were identified who had experienced reproductive health outcomes. The
      Medicaid file was linked to a Child Protective Services database and a Juvenile
      Justice database to identify episodes of abuse by a caretaker and criminal
      behavior. RESULTS: Of 21,350 Alaskan females aged 10-15 years enrolled in
      Medicaid during 1999-2003, 841 (3.9%) presented for reproductive health care,
      2,930 (14%) were referred to Child Protective Services and 1,858 (8.7%) were
      referred to Juvenile Justice for criminal activity. Among the subjects with a
      reproductive health-related claim, 39% were referred to Child Protective Services
      while 31% were referred to Juvenile Justice at some point during the study
      period. Reproductive health care was strongly associated with referral to Child
      Protective Services (adjusted odds ratio [aOR] 2.9, 95% confidence interval [CI]
      2.5-3.4), substantiated sexual abuse (aOR 2.3, 95% CI 1.7-3.2), and referral to
      Juvenile Justice (aOR 2.9, 95% CI 2.5-3.4). These associations remained
      regardless of the type of reproductive health care, including contraceptive
      management. CONCLUSION: Females aged 10-15 years enrolled in Medicaid who present
      for any type of reproductive health care are at increased risk of abuse by a
      caretaker and criminal behavior. Clinicians caring for low-income females should
      consider routine screening for sexual activity and the experience of violence.
      LEVEL OF EVIDENCE: II-2.

PMID- 16816065
TI  - Efficacy of intrauterine lidocaine for removal of a "lost" intrauterine device: a
      randomized, controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of intrauterine lidocaine instillation in
      reducing patient discomfort during the removal of a "lost" intrauterine device
      (IUD). METHODS: This double-blinded, randomized, placebo-controlled trial
      included 68 women who underwent removal procedure for a "lost" IUD. Thirty-four
      women were allocated to the lidocaine group and 34 to the saline group. The main
      outcome measure was the intensity of pain during, immediately after, and 20
      minutes after the procedure, assessed by a visual analog scale. Statistical
      analysis was performed using the Friedman test with Bonferroni correction,
      Student t test, and chi2. RESULTS: There were no statistically significant
      differences between the study group and the control group in mean age, parity
      history of chronic pelvic pain and dysmenorrhea, history of curettage, education,
      socioeconomic status, menopausal status, breastfeeding, type of IUD, and duration
      of IUD. Pain scores demonstrated a significant difference between groups during
      the procedure (placebo 6.41 +/- 1.15, lidocaine 5.23 +/- 0.69, P < .01),
      immediately after procedure (placebo 6.05 +/- 1.01, lidocaine 4.94 +/- 0.60, P <
      .01), and 20 minutes after procedure (placebo 4.32 +/- 0.63, lidocaine 4.44 +/-
      0.66, P < .01). The number needed to treat was 3 (95% confidence interval 2-9).
      CONCLUSION: Intrauterine lidocaine appears to be effective in decreasing pain in
      women undergoing the removal procedure of a "lost" IUD. CLINICAL TRIAL
      REGISTRATION: Clinicaltrials.gov, NCT00308841. LEVEL OF EVIDENCE: I.

PMID- 16816066
TI  - Trial of labor or repeat cesarean delivery in women with morbid obesity and
      previous cesarean delivery.
AB  - OBJECTIVE: Assess effects of body mass index (BMI) on trial of labor after
      previous cesarean delivery and determine whether morbidly obese women have
      greater maternal and perinatal morbidity with trial of labor compared with
      elective repeat cesarean delivery. METHODS: Secondary analysis from a prospective
      observational study included all term singletons undergoing trial of labor after
      previous cesarean delivery. Body mass index groups were as follows: normal 18.5
      24.9, overweight 25.0-29.9, obese 30.0-39.9, morbidly obese 40.0 kg/m2 or
      greater, and were compared for failure and maternal and neonatal morbidities. The
      morbidly obese trial of labor and elective repeat cesarean delivery were compared
      for maternal and neonatal morbidities. Multivariable logistic regression analysis
      controlled for confounding variables. RESULTS: There were 14,142 trial of labor
      participants and 14,304 elective repeat cesarean delivery participants.
      Increasing BMI was directly associated with failed trial of labor after previous
      cesarean delivery: from 15.2% in normal weight (1,344) to 39.3% in morbidly obese
      (1,638), with combined risk of rupture/dehiscence increasing from 0.9% to 2.1% in
      morbidly obese women. Among morbidly obese women, trial of labor carried greater
      than five-fold risk of uterine rupture/dehiscence (2.1% versus 0.4%), almost a
      two-fold increase in composite maternal morbidity (7.2% versus 3.8%) and five
      fold risk of neonatal injury (1.1% versus 0.2%) (fractures, brachial plexus
      injuries, and lacerations), but no neonatal encephalopathy. Morbidly obese women
      failing a trial of labor had six-fold greater composite maternal morbidity than
      those undergoing a successful trial of labor (14.2% versus 2.6%). CONCLUSION:
      Body mass index correlates with outcomes in trial of labor after previous
      cesarean delivery. Morbidly obese women undergoing a trial of labor were at
      increased risk for failure. Increased BMI was associated with greater composite
      morbidity and neonatal injury compared with elective repeat cesarean delivery,
      but absolute morbidities were small. Increased risks should be considered before
      trial of labor after previous cesarean delivery. LEVEL OF EVIDENCE: II-2.

PMID- 16816067
TI  - Effect of coitus at term on length of gestation, induction of labor, and mode of
      delivery.
AB  - OBJECTIVE: To determine coital incidence at term and to estimate its effect on
      labor onset and mode of delivery. METHODS: Healthy women with uncomplicated
      pregnancies and established gestational age were recruited to keep a diary of
      coital activity from 36 weeks of gestation until birth and to answer a short
      questionnaire. Two hundred women with complete coital diaries were available for
      analysis. Outcome measures include coitus, postdate pregnancy (defined as
      pregnancy beyond the estimated date of confinement), gestational length of at
      least 41 weeks, labor induction at 41 weeks of gestation, and mode of delivery
      RESULTS: Reported sexual intercourse at term was influenced by a woman's
      perception of coital safety, her ethnicity, and her partner's age. After
      multivariable logistic regression analysis controlling for the women's ethnicity,
      education, occupation, perception of coital safety, and partner's age, coitus at
      term remained independently associated with reductions in postdate pregnancy
      (adjusted odds ratio [AOR] 0.28, 95% confidence interval [CI] 0.13-0.58, P =
      .001), gestational length of at least 41 weeks (AOR 0.10, 95% CI 0.04-0.28, P <
      .001), and requirement for labor induction at 41 weeks of gestation (AOR 0.08,
      95% CI 0.03-0.26, P < .001). At 39 weeks of gestation, 5 (95% CI 3.3-10.3)
      couples needed to have intercourse to avoid one woman having to undergo labor
      induction at 41 weeks of gestation. Coitus at term had no significant effect on
      operative delivery (adjusted P = .15). CONCLUSION: Reported sexual intercourse at
      term was associated with earlier onset of labor and reduced requirement for labor
      induction at 41 weeks. LEVEL OF EVIDENCE: II-2.

PMID- 16816069
TI  - Plasma and tissue expression of the long pentraxin 3 during normal pregnancy and
      preeclampsia.
AB  - OBJECTIVE: Cell death normally occurs during pregnancy and is critical during its
      common complication, preeclampsia. The long pentraxin 3 (PTX3) gene is generated
      in tissues that cope with excessive or deregulated cell death and inhibits the
      cross-presentation of cell-associated antigens. We examined whether PTX3 is
      expressed during pregnancy and possibly involved in the development of
      preeclampsia. METHODS: Women with preeclampsia (n = 30), women with uncomplicated
      pregnancies (n = 66), age-matched healthy women (n = 50), women who developed
      acute bacterial infections (n = 20), and women with rheumatoid arthritis (n = 20)
      were studied. The concentrations of PTX3 were measured in the blood by a sandwich
      enzyme-linked immunosorbent assay (ELISA) and in placentas by
      immunohistochemistry. The concentrations of PTX3 and C-reactive protein in the
      various groups were compared by nonparametric tests (the Mann-Whitney U and the
      Kruskal-Wallis tests). The odds of developing preeclampsia were assessed using
      logistic regression. RESULTS: PTX3 was expressed in amniotic epithelium and
      chorionic mesoderm, trophoblast terminal villi, and perivascular stroma in
      placentas from pregnancies of uncomplicated subjects. Circulating levels steadily
      rose during normal gestation and peaked during labor. Serum levels of PTX3 were
      strikingly higher in preeclampsia compared with normal control pregnancies (5.08
      +/- 1.34 and 0.59 +/- 0.07 ng/mL, respectively, P < .001). Sites of higher
      expression in the placentas from preeclamptic patients include infarcts and
      fibrinoid zones. CONCLUSION: Defects in the homeostatic response to cell
      death/remodeling events, revealed by enhanced levels of PTX3, could be implicated
      in preeclampsia. LEVEL OF EVIDENCE: II-2.

PMID- 16816068
TI  - Valacyclovir prophylaxis to prevent recurrent herpes at delivery: a randomized
      clinical trial.
AB  - OBJECTIVE: To measure the efficacy of valacyclovir suppression in late pregnancy
      to reduce the incidence of recurrent genital herpes in labor and subsequent
      cesarean delivery. METHODS: A total of 350 pregnant women with a history of
      genital herpes were assigned randomly to oral valacyclovir 500 mg twice a day or
      an identical placebo from 36 weeks of gestation until delivery. In labor,
      vulvovaginal herpes simplex virus (HSV) culture and polymerase chain reaction
      (PCR) specimens were collected. Vaginal delivery was permitted if no clinical
      recurrence or prodromal symptoms were present. Neonatal HSV cultures and
      laboratory tests were obtained, and infants were followed up for 1 month after
      delivery. Data were analyzed using chi2 and Student t tests. RESULTS: One hundred
      seventy women treated with valacyclovir and 168 women treated with placebo were
      evaluated. Eighty-two percent of the women had recurrent genital herpes; 12% had
      first episode, nonprimary genital herpes; and 6% had first episode, primary
      genital herpes. At delivery, 28 women (8%) had recurrent genital herpes requiring
      cesarean delivery: 4% in the valacyclovir group and 13% in the placebo group (P =
      .009). Herpes simplex virus was detected by culture in 2% of the valacyclovir
      group and 9% [corrected] of the placebo group (P =.02). No infants were diagnosed
      with neonatal HSV, and there were no significant differences in neonatal
      complications. There were no significant differences in maternal or obstetric
      complications in either group. CONCLUSION: Valacyclovir suppression after 36
      weeks of gestation significantly reduces HSV shedding and recurrent genital
      herpes requiring cesarean delivery. LEVEL OF EVIDENCE: I.

PMID- 16816070
TI  - Fostering harmony in labor and delivery: a nursing preceptorship for clinical
      clerks.
AB  - OBJECTIVE: The relationship between the specialized nurses of the Labor and
      Delivery Suite and the medical students who are rotating through the unit as
      clinical clerks has traditionally been a poor one. The objective of this project
      was to develop a program which pairs medical students with nurse preceptors to
      improve their understanding of each other's roles and to provide students with an
      opportunity to gain basic clinical skills, and secondarily, to evaluate the
      students' perceptions of the program METHODS: We developed an ongoing program
      which pairs third-year students with Labor and Delivery nurses for one to two
      shifts. The evaluation of the program used the end-of-rotation questionnaire
      completed anonymously by students to determine their rating. RESULTS: The median
      rating of the program by students is 5 out of 7 (with 7 being the best rating).
      Seventy-seven percent rated the program 5 or higher. CONCLUSION: This program has
      been successful in pairing students with nurse preceptors for a total of three
      years so far. The process we used to develop the program may help other
      institutions who wish to put in place a similar program. LEVEL OF EVIDENCE: III.

PMID- 16816072
TI  - Comparative outcomes of bladder cancer.
AB  - OBJECTIVE: To compare the survival of women and men with transitional cell
      bladder cancer. METHODS: We used the Surveillance Epidemiology and End Results
      database to identify patients aged 35 years or older diagnosed with bladder
      cancer between 1991 and 2001 actively followed up. We excluded cases diagnosed by
      autopsy or death certificates and those of unknown race. We used Cox proportional
      hazard regression to analyze survival in patients with advanced disease. RESULTS:
      Of the 31,009 patients meeting eligibility criteria, 26.7% were women. Median age
      at diagnosis for women and men was 72 and 70 years, respectively. Regional
      disease was diagnosed in 20.3% of white women and 35.5% of African-American
      women, compared with only 17.6% of white men and 25.9% of African-American men (P
      < .001). Increased age, African-American race, and being female significantly
      increased the hazard of death (hazard ratio [HR] 1.037, 95% confidence interval
      [CI] 1,034-1.041; HR 1.402, 95% CI 1.187-1.656; and HR 1.842, 95% CI 1.158
      2.931). CONCLUSION: Women with bladder cancer, particularly African-Americans,
      have shorter survival. This is partially explained by higher risk of diagnosis
      with poorly differentiated tumors, advanced stage, and advanced age. Women should
      be targeted for timely diagnosis. LEVEL OF EVIDENCE: II-2.

PMID- 16816071
TI  - Genetic polymorphism in the fibrinolytic system and endometriosis.
AB  - OBJECTIVE: Although most women experience retrograde menses during their
      reproductive life, endometriosis develops only in a small percentage. We
      hypothesized that persistence of a fibrin matrix in peritoneal pockets, as a
      result of hypofibrinolysis, could allow menstrually deposited endometrial
      fragments to initiate endometriosis. Fibrinolysis is modulated by several
      factors, and polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) gene
      are considered to be one of the important determinants. The objective of this
      study was to evaluate PAI-1 genotypes in a group of women with or without
      endometriosis. METHODS: In 118 women (75 with laparoscopically confirmed
      endometriosis and 43 controls), genomic DNA was extracted from blood and the PAI
      1 promoter genotype was determined by polymerase chain reaction amplification of
      DNA using specific primers for the 4G or 5G allele followed by gel
      electrophoresis. A portion of the polymerase chain reaction product was purified
      and sequenced to confirm the gel electrophoresis results. RESULTS: Endometriosis
      was more likely in patients with 4G/5G (odds ratio 38; 95% confidence interval
      [CI] 6-229) or 4G/4G (odds ratio 441; 95% CI 53-3,694) compared with 5G/5G PAI-1
      genotype. Fifty-two of 75 women with endometriosis (69 %, 95% CI 58-79%) had the
      4G/4G genotype compared with only 5 of 43 (12%; 95% CI 4-25%) controls. In
      contrast, the 5G/5G genotype associated with normal fibrinolysis was found in 2
      of 75 (3%; 95% CI 0-9%) women with endometriosis compared with 24 of 43 (56%; 95%
      CI 40-71%) controls. CONCLUSION: Hypofibrinolysis, associated with the 4G allele
      of the PAI-1 gene, was found significantly more often in women with endometriosis
      compared with controls. Persistence of fibrin matrix could support the initiation
      of endometriotic lesions in the peritoneal cavity, explaining why some women with
      retrograde menstruation develop endometriosis while others do not. LEVEL OF
      EVIDENCE: II-2.

PMID- 16816073
TI  - Gestational trophoblastic disease.
AB  - This review summarizes the primary management of molar pregnancies, surveillance
      after evacuation, and the evaluation and management of malignant gestational
      trophoblastic neoplasia (GTN). Most women with gestational trophoblastic disease
      can be successfully managed with preservation of their normal reproductive
      function. It is important to manage molar pregnancies properly to minimize acute
      complications and identify malignant sequelae promptly. Current International
      Federation of Gynecology and Obstetrics (FIGO) guidelines for making the
      diagnosis and staging of GTN allow uniformity for reporting results of treatment.
      It is important to individualize treatment for women with malignant GTN based
      upon risk factors, using less toxic therapy for patients with low-risk disease
      and aggressive multiagent therapy for those with high-risk disease. Patients with
      malignant GTN should be managed in consultation with an individual experienced in
      the complex, multimodality treatment of these patients.

PMID- 16816074
TI  - A surprising postnatal diagnosis.

PMID- 16816078
TI  - Professional liability payments in obstetrics and gynecology.

PMID- 16816079
TI  - Professional liability payments in obstetrics and gynecology.

PMID- 16816080
TI  - Pulmonary embolism after major abdominal surgery in gynecologic oncology.

PMID- 16816081
TI  - Pulmonary embolism after major abdominal surgery in gynecologic oncology.

PMID- 16816082
TI  - Health policy considerations for our sexual minority patients.

PMID- 16816083
TI  - Health policy considerations for our sexual minority patients.

PMID- 16816084
TI  - A rare case of precoccygeal endometriosis.

PMID- 16816087
TI  - ACOG Practice Bulletin No. 74. Antibiotic prophylaxis for gynecologic procedures.
AB  - Surgical site inflection remains the most common surgical complication. Up to 5%
      of operative patients will develop a surgical site infection leading to a longer
      hospital stay and increased cost. One of the advances in infection control
      practices has been the selective use of antibiotic prophylaxis.
      However,antibiotic use, especially prophylactic antibiotic use, has been
      associated with the selection of antibiotic-resistant bacteria. Indiscriminate
      use of prophylactic antibiotics for institutions as well as for individual
      patients promotes this dangerous side eject. There are acknowledged consequences
      of prophylactic antibiotic use for institutions as well as for individual
      patients. It is important for clinicians to understand when antibiotic
      prophylaxis is indicated and when it is inappropriate. The purpose of this
      document is to review the evidence for surgical site infection prevention and
      appropriate antibiotic prophylaxis for gynecologic procedures.

PMID- 16816088
TI  - ACOG Committee Opinion No. 340. Mode of term singleton breech delivery.
AB  - In light of recent studies that further clarify the long-term risks of vaginal
      breech delivery, the American College of Obstetricians and Gynecologists
      recommends that the decision regarding mode of delivery should depend on the
      experience of the health care provider Cesarean delivery will be the preferred
      mode for most physicians because of the diminish-ing expertise in vaginal breech
      delivery. Planned vaginal delivery of a term singleton breech fetus may be
      reasonable under hospital-specific protocol guidelines for both eligibility and
      labor management. Before a vaginal breech delivery is planned, women should be
      informed that the risk of peri-natal or neonatal mortality or short-term serious
      neonatal morbidity may be higher than if a cesarean delivery is planned, and the
      patient's informed con-sent should be documented.

PMID- 16816089
TI  - ACOG Committee Opinion No. 341. Ethical ways for physicians to market a practice.
AB  - It is ethical for physicians to market their practices through any form of public
      communication provided that the communication is truthful and not misleading or
      deceptive. Communications should not convey discriminatory attitudes involving
      race, ethnicity, gender; or sexual orientation.All paid advertising must be
      clearly identified as such. Producing fair and accurate advertising of medical
      practices and services can be challenging. It often is difficult to include
      detailed information because of cost and size restrictions or the limitations of
      the media form that has been selected. If the specific advertising form does not
      lend itself to clear and accurate description, an alternative media format should
      be selected. Finally, any advertising that seeks to denigrate the competence of
      other individual professionals or group practices is always considered unethical.

PMID- 16816090
TI  - A Cartesian reflex assessment of face processing.
AB  - Commands to blink were embedded within pictures of faces and simple geometric
      shapes or forms. The faces and shapes were conditioned stimuli (CSs), and the
      required responses were conditioned responses, or more properly, Cartesian
      reflexes (CRs). As in classical conditioning protocols, response times (RTs) were
      measured from CS onset. RTs provided a measure of the processing cost (PC) of
      attending to a CS. A PC is the extra time required to respond relative to RTs to
      unconditioned stimulus (US) commands presented alone. They reflect the interplay
      between attentional processing of the informational content of a CS and its
      signaling function with respect to the US command. This resulted in longer RTs to
      embedded commands. Differences between PCs of faces and geometric shapes
      represent a starting place for a new mental chronometry based on the traditional
      idea that differences in RT reflect differences in information processing.

PMID- 16816091
TI  - Dimensions of cognition in an insect, the honeybee.
AB  - This review provides evidence for the enormous richness of insect behavior, its
      high flexibility, and the cross-talk between different behavioral routines. The
      memory structure established by multiple forms of learning represents sensory
      inputs and relates behaviors in such a way that representations of complex
      environmental conditions are formed. Navigation and communication in social
      hymenoptera are particularly telling examples in this respect, but it is fair to
      conclude that similar integrated forms of dealing with the environment will be
      found in other insects when they are studied more closely. In this sense,
      research addressing behavioral complexity and its underlying neural substrates is
      necessary to characterize the real potential of insect learning and memory.
      Usually, such an approach has been used to characterize behavioral simplicity
      rather than complexity. It seems therefore timely to focus on the latter by
      studying problem solving alongside and in addition to elemental forms of
      learning.

PMID- 16816093
TI  - Time for a rigorous performance improvement curriculum for emergency medicine
      residents.

PMID- 16816094
TI  - Hemothorax after a stab wound to the chest, with clear breath sounds and a normal
      radiograph.

PMID- 16816092
TI  - What is the functional significance of chronic stress-induced CA3 dendritic
      retraction within the hippocampus?
AB  - Chronic stress produces consistent and reversible changes within the dendritic
      arbors of CA3 hippocampal neurons, characterized by decreased dendritic length
      and reduced branch number. This chronic stress-induced dendritic retraction has
      traditionally corresponded to hippocampus-dependent spatial memory deficits.
      However, anomalous findings have raised doubts as to whether a CA3 dendritic
      retraction is sufficient to compromise hippocampal function. The purpose of this
      review is to outline the mechanism underlying chronic stress-induced CA3
      dendritic retraction and to explain why CA3 dendritic retraction has been thought
      to mediate spatial memory. The anomalous findings provide support for a modified
      hypothesis, in which chronic stress is proposed to induce CA3 dendritic
      retraction, which then disrupts hypothalamic-pituitary-adrenal axis activity,
      leading to dysregulated glucocorticoid release. The combination of hippocampal
      CA3 dendritic retraction and elevated glucocorticoid release contributes to
      impaired spatial memory. These findings are presented in the context of clinical
      conditions associated with elevated glucocorticoids.

PMID- 16816095
TI  - Resident portfolio: "She was hideous"--the effect of negative emotions on
      physician-patient interaction.

PMID- 16816098
TI  - The left-without-being-seen rate: an imperfect measure of emergency department
      crowding.

PMID- 16816099
TI  - NIH funding: not a prayer.

PMID- 16816100
TI  - A prize for the foreign-born.

PMID- 16816101
TI  - Does bias in science hold women back?

PMID- 16816102
TI  - What's happening to the new investigator?

PMID- 16816103
TI  - Does a "500 million-year-old hormone" disprove Darwin?

PMID- 16816104
TI  - A brief history of RNAi: the silence of the genes.
AB  - The use of the RNA interference (RNAi) pathway to eliminate gene products has
      greatly facilitated the understanding of gene function. Behind this remarkable
      pathway is an intricate network of proteins that ensures the degradation of the
      target mRNA. In this review, we explore the history of RNAi as well as
      highlighting recent discoveries.

PMID- 16816105
TI  - DNA precursor metabolism and genomic stability.
AB  - Intracellular concentrations of the four deoxyribonucleoside triphosphates
      (dNTPs) are closely regulated, and imbalances in the four dNTP pools have
      genotoxic consequences. Replication errors leading to mutations can occur, for
      example, if one dNTP in excess drives formation of a non-Watson-Crick base pair
      or if it forces replicative DNA chain elongation past a mismatch before DNA
      polymerase can correct the error by 3' exonuclease proofreading. This review
      focuses on developments since 1994, when the field was last reviewed
      comprehensively. Emphasis is placed on the following topics: 1) novel aspects of
      dNTP pool regulation, 2) dNTP pool asymmetries as mutagenic determinants, 3) dNTP
      metabolism and hypermutagenesis of retroviral genomes, 4) dNTP metabolism and
      mutagenesis in the mitochondrial genome, 5) chemical modification of nucleotides
      as a premutagenic event, 6) relationships between dNTP metabolism, genome
      stability, aging, and cancer.

PMID- 16816106
TI  - LPS regulates proinflammatory gene expression in macrophages by altering histone
      deacetylase expression.
AB  - Bacterial LPS triggers dramatic changes in gene expression in macrophages. We
      show here that LPS regulated several members of the histone deacetylase (HDAC)
      family at the mRNA level in murine bone marrow-derived macrophages (BMM). LPS
      transiently repressed, then induced a number of HDACs (Hdac-4, 5, 7) in BMM,
      whereas Hdac-1 mRNA was induced more rapidly. Treatment of BMM with trichostatin
      A (TSA), an inhibitor of HDACs, enhanced LPS-induced expression of the Cox-2,
      Cxcl2, and Ifit2 genes. In the case of Cox-2, this effect was also apparent at
      the promoter level. Overexpression of Hdac-8 in RAW264 murine macrophages blocked
      the ability of LPS to induce Cox-2 mRNA. Another class of LPS-inducible genes,
      which included Ccl2, Ccl7, and Edn1, was suppressed by TSA, an effect most likely
      mediated by PU.1 degradation. Hence, HDACs act as potent and selective negative
      regulators of proinflammatory gene expression and act to prevent excessive
      inflammatory responses in macrophages.

PMID- 16816107
TI  - Aspirin regulates expression and function of scavenger receptor-BI in
      macrophages: studies in primary human macrophages and in mice.
AB  - Scavenger receptor class B type I (SR-BI) has been shown to be expressed in human
      atherosclerotic plaque macrophages, where it is believed to reduce
      atherosclerosis by promoting cholesterol efflux. In this study we investigated
      the influence of aspirin and other NSAIDs on SR-BI expression and function in
      cultured human macrophages as well as in different mouse strains. Incubation of
      human macrophages with 0.5 mmol/l aspirin resulted in increased SR-BI protein
      expression and increased uptake of HDL-associated [3H]cholesteryl oleate without
      changes of SR-BI mRNA levels. In contrast, using 5 mmol/l of aspirin, SR-BI
      expression and function were significantly decreased. Sodium salicylate exerted
      similar effects on SR-BI expression, whereas no effects were observed using known
      COX1/2 inhibitors ibuprofen and naproxen, respectively. In in vivo studies low
      dose aspirin treatment (6 mg/kg.day) induced SR-BI expression in wild-type and
      PPAR-alpha knockout mice, respectively, whereas the opposite effect was observed
      upon high-dose aspirin treatment (60 mg/kg.day) in these animals. We could show
      that COX-independent effects of aspirin were able to enhance expression of SR-BI
      in macrophages in a post-transcriptional, PPAR-alpha independent way, suggesting
      a novel pharmacologic effect of aspirin.

PMID- 16816109
TI  - Bovine CD14 receptor produced in plants reduces severity of intramammary
      bacterial infection.
AB  - CD14 is a high-affinity receptor protein for the complex of bacterial LPS (LPS)
      and LPS binding protein in animals. Binding of the soluble form of CD14 (sCD14)
      to LPS, found in the outer membrane of Escherichia coli and other Gram-negative
      bacteria, enhances host innate immune responses, reduces the severity of
      mastitis, and facilitates clearance and neutralization of LPS, thus protecting
      against an excessive immune response to LPS and development of endotoxic shock. A
      truncated form of sCD14, carrying a histidine residue affinity tag for
      purification, was incorporated into Potato virus X for transient expression in
      Nicotiana benthamiana plants. Western blots probed with CD14-specific antibodies
      demonstrated that crude plant extracts and affinity-purified samples contained
      immunoreactive sCD14. Biological activity of plant-derived recombinant bovine
      sCD14 (PrbosCD14) was demonstrated in vitro by LPS-induced apoptosis and
      interleukin (IL) -8 production in bovine endothelial cells, and in vivo by
      enhancement of LPS-induced neutrophil recruitment. Finally, in PrbosCD14-infused
      glands subsequently infected with E. coli, lower numbers of viable bacteria were
      recovered and there was an absence of clinical symptoms, demonstrating
      prophylactic efficacy of PrbosCD14. This is the first report of a functionally
      active animal receptor protein made in plants and the prophylactic use of a plant
      derived protein to reduce the severity of bacterial infections in animals.

PMID- 16816108
TI  - Common genetic polymorphisms affect the human requirement for the nutrient
      choline.
AB  - Humans eating diets deficient in the essential nutrient choline can develop organ
      dysfunction. We hypothesized that common single nucleotide polymorphisms (SNPs)
      in genes involved in choline metabolism influence the dietary requirement of this
      nutrient. Fifty-seven humans were fed a low choline diet until they developed
      organ dysfunction or for up to 42 days. We tested DNA SNPs for allelic
      association with susceptibility to developing organ dysfunction associated with
      choline deficiency. We identified an SNP in the promoter region of the
      phosphatidylethanolamine N-methyltransferase gene (PEMT; -744 G-->C; rs12325817)
      for which 18 of 23 carriers of the C allele (78%) developed organ dysfunction
      when fed a low choline diet (odds ratio 25, P=0.002). The first of two SNPs in
      the coding region of the choline dehydrogenase gene (CHDH; +318 A-->C; rs9001)
      had a protective effect on susceptibility to choline deficiency, while a second
      CHDH variant (+432 G-->T; rs12676) was associated with increased susceptibility
      to choline deficiency. A SNP in the PEMT coding region (+5465 G-->A; rs7946) and
      a betaine:homocysteine methyltransferase (BHMT) SNP (+742 G-->A; rs3733890) were
      not associated with susceptibility to choline deficiency. Identification of
      common polymorphisms that affect dietary requirements for choline could enable us
      to identify individuals for whom we need to assure adequate dietary choline
      intake.

PMID- 16816110
TI  - Inhibition of prostaglandin E2 synthesis by SC-560 is independent of
      cyclooxygenase 1 inhibition.
AB  - Prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2) and microsomal
      prostaglandin E2 synthase-1 (mPGES-1) plays an important role in the
      pathophysiology of inflammation, pain, and fever. We investigated the actions of
      TNFalpha toward stimulation of PGE2 synthesis in primary spinal cord neurons.
      TNFalpha induced COX-2 and mPGES-1 expression in neurons, followed by formation
      of PGE2, which was blocked by a selective COX-2 inhibitor. Surprisingly, the
      "selective COX-1" inhibitor SC-560 completely inhibited TNFalpha-induced PGE2
      synthesis in neurons at nanomolar concentrations. Moreover, SC-560 inhibited PGE2
      and thromboxane A2 synthesis in human monocytes and platelets with IC50 of 1.8 nM
      and 2.5 nM, respectively. SC-560 treatment neither altered TNFalpha-induced COX-2
      or mPGES-1 expression nor did the addition of the calcium ionophore A23187 or
      arachidonic acid reverse the inhibition by SC-560. Moreover, no influence of SC
      560 on PGE2 synthase activities or PGE2 transport was seen. Most importantly, SC
      560 blocked TNFalpha-induced PGE2 synthesis in COX-1-deficient spinal cord
      neurons, demonstrating a COX-1-independent inhibition of PGE2 synthesis. Although
      SC-560 inhibited LPS-induced PGE2 synthesis in neurons and RAW264.7 macrophages
      in whole cell assays, no inhibition was observed in lysates of the same cells.
      Taken together our data demonstrate that SC-560 acts at least in some cell types
      as an unselective COX inhibitor despite its selectivity toward COX-1 under cell
      free conditions.

PMID- 16816111
TI  - Increased BACE1 maturation contributes to the pathogenesis of Alzheimer's disease
      in Down syndrome.
AB  - Almost all Down syndrome (DS) patients develop characteristic Alzheimer's disease
      (AD) neuropathology, including neuritic plaques and neurofibrillary tangles,
      after middle age. The mechanism underlying AD neuropathology in DS has been
      unknown. Abeta is the central component of neuritic plaques and is generated from
      APP by cleavage by the beta- and gamma-secretases. Here we show that beta
      secretase activity is markedly elevated in DS. The ratio of mature to immature
      forms of BACE1 is altered in DS. DS has significantly higher levels of mature
      BACE1 proteins in Golgi than normal controls. Time-lapse live image analysis
      showed that BACE1 proteins were predominantly immobile in Golgi in DS cells,
      while they underwent normal trafficking in controls. Thus, overproduction of
      Abeta in DS is caused by abnormal BACE1 protein trafficking and maturation. Our
      results provide a novel molecular mechanism by which AD develops in DS and
      support the therapeutic potential of inhibiting BACE1 in AD and DS.

PMID- 16816112
TI  - BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of
      Alzheimer's disease in Down syndrome.
AB  - Amyloid beta protein (Abeta), the major component of neuritic plaques in
      Alzheimer's disease (AD), is derived from APP by sequential cleavages of beta-
      and gamma-secretases. Beta-site APP cleaving enzyme 1 (BACE1) is the major beta
      secretase in vivo. Beta-site APP cleaving enzyme 2 (BACE2) is the homologue of
      BACE1. The majority of people with Down syndrome (DS), also called Trisomy 21
      syndrome, will develop AD neuropathology after middle age. We and others have
      shown that APP C99, the major beta-secretase product, and Abeta are markedly
      increased in DS. Since BACE2 is located on chromosome 21, it is speculated that
      BACE2 may play a role in AD pathogenesis in DS. In this report we found that
      BACE2 cleaves APP at a novel theta site downstream of the alpha site, abolishing
      Abeta production. Overexpression of BACE2 by lentivirus markedly reduced Abeta
      production in primary neurons derived from Swedish mutant APP transgenic mice.
      Despite an extra copy of the BACE2 gene in DS and the increase of its
      transcription, BACE2 protein levels are unchanged. Our data clearly demonstrate
      that BACE2, as a novel theta-secretase to cleave APP within the Abeta domain, is
      not involved in the AD pathogenesis of DS patients; instead, therapeutic
      interventions that potentiate BACE2 may prevent AD pathogenesis.

PMID- 16816113
TI  - Neuroprotective effect of mifepristone involves neuron depolarization.
AB  - In several regions of the developing nervous system, neurons undergo programmed
      cell death. In the rat cerebellum, Purkinje cell apoptosis is exacerbated when
      cerebellar slices are cultured during the first postnatal week. To understand the
      mechanism of this developmental apoptosis, we took advantage of its inhibition by
      the steroid analog mifepristone. This effect did not involve the classical
      steroid nuclear receptors. Microarray analysis revealed that mifepristone down
      regulated mRNA levels of the Na+/K+-ATPase alpha3 subunit more than three times.
      Consistent with the down-regulation of the Na+/K+-ATPase, mifepristone caused
      Purkinje cell membrane depolarization. Depolarizing agents like ouabain (1
      microM), tetraethylammonium (2 mM), and veratridine (2 microM) protected Purkinje
      cells from apoptosis. These results suggest a role of excitatory inputs in
      Purkinje cell survival during early postnatal development. Indeed, coculturing
      cerebellar slices with glutamatergic inferior olivary neuron preparations allowed
      rescue of Purkinje cells. These findings reveal a new neuroprotective mechanism
      of mifepristone and support a pivotal role for excitatory inputs in the survival
      of Purkinje neurons. Mifepristone may be a useful lead compound in the
      development of novel therapeutic approaches for maintaining the resting potential
      of neurons at values favorable for their survival under neuropathological
      conditions.

PMID- 16816114
TI  - Reactive oxygen species mediates disialoganglioside GD3-induced inhibition of
      ERK1/2 and matrix metalloproteinase-9 expression in vascular smooth muscle cells.
AB  - Sialic acid containing glycosphingolipids (gangliosides) are thought to play
      important roles in the function of various biological phenomena such as
      atherosclerosis. We have previously shown that the overexpression of the
      disialoganglioside (GD3) synthase gene effectively suppresses cell proliferation,
      cell cycle progression, and MMP-9 expression in vascular smooth muscle cells
      (VSMC). However, the issue of how the overexpression of GD3 synthase gene results
      in the inhibition of cellular responses in VSMC remains unclear. The findings
      herein demonstrate that overexpression of the GD3 synthase gene suppresses VSMC
      responses through the generation of reactive oxygen species (ROS). Superoxide and
      hydrogen peroxide were generated at increased levels in GD3 synthase gene
      transfectants in comparison with empty vector (EV) -transfected VSMC. This
      phenomenon was blocked by antioxidants such as N-acetyl-L-cysteine (NAC) and
      pyrrolidine dithiocarbamate (PDTC). Increased ROS generation was associated with
      a decreased endogenous antioxidant activity, increased lipid peroxidation, and
      mitochondrial DNA damage. Further studies revealed that the blockade of ROS
      function with antioxidants reversed the effect of GD3 synthase gene
      overexpression on VSMC proliferation and cell cycle regulation in response to
      platelet-derived growth factor (PDGF). In addition, we found that treatment with
      antioxidants reversed the decreased matrix metalloproteinase-9 (MMP-9) expression
      in response to TNF-alpha as determined by zymography and immunoblot in GD3
      synthase gene transfectants. This recovery effect was characterized by the up
      regulation of MMP-9 promoter activity, which was transcriptionally regulated at
      NF-kappaB and activation protein-1 (activating protein (AP) -1) sites in the MMP
      9 promoter. These findings suggest that ROS may play a role in GD3 synthase gene
      mediated VSMC phenotypic changes that may contribute to plaque instability in
      atherosclerosis.

PMID- 16816115
TI  - Structural basis of the cross-reaction between an antibody to the Trypanosoma
      cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor.
AB  - Antibodies from patients with Chagas heart disease and monoclonal antibodies (or
      mAb) to the carboxy-terminal end (B cell epitope R13) of the ribosomal P2beta
      protein of Trypanosoma cruzi (TcP2beta) cross-react with the beta1 adrenergic
      receptor (beta1-AR). Two single-chain Fv fragments (scFv) C5 and B7 derived from
      the variable regions of the anti-R13 mAb 17.2 were expressed. scFv C5 was a dimer
      and bound to TcP2beta with an affinity of K(d) = 8 nM, whereas scFv B7 was
      monomeric and had less affinity than scFv C5 for TcP2beta, K(d) = 46 nM. The
      affinity constant of scFv C5 to the second extracellular loop of the human beta1
      AR was of 10 microM. Moreover, scFv C5 induced an increase in cAMP levels of CHO
      K cells transfected with the human beta1-AR; scFv B7 had no effect but blocked
      isoproterenol stimulation. The agonist-like activity of scFv C5 and the
      antagonist activity of scFv B7 were both confirmed in vivo on heart beating
      frequency after their passive transfer to mice. Molecular modeling of the
      variable region of mAb 17.2 indicated which amino acids were likely to be
      involved in recognizing both peptide EDDDMGFGLF, derived from the R13 epitope of
      TcP2beta, and peptide ESDEARRCYN from the second extracellular loop of the human
      beta1-AR. It is plausible that the recently described cross-reaction of mAb 17.2
      with rhodopsin can also be explained by this model. The physiological effects of
      this type of anti-T. cruzi antibodies may increase the liability of patients with
      Chagas disease.

PMID- 16816116
TI  - Therapeutic activity of C5a receptor antagonists in a rat model of
      neurodegeneration.
AB  - The complement system is thought to be involved in the pathogenesis of numerous
      neurological diseases, although its precise role remains controversial. In this
      study we used orally active C5a receptor antagonists (PMX53 and PMX205) developed
      in our laboratories in a rat model of 3-nitropropionic acid (3-NP) -induced
      Huntington's disease. Administration of the C5a antagonists (10 mg/kg/day, oral)
      either 48 h pre- or 48 h post-toxin significantly reduced body weight loss,
      anorexia, and behavioral and motor deficits associated with 3-NP intoxication.
      Striatal lesion size, apoptosis, neutrophil infiltration, and hemorrhage were
      also significantly reduced in C5a antagonist-treated rats. Immunohistochemical
      analysis demonstrated marked deposition of C3 and C9, and up-regulation of C5a
      receptors on neuronal cells at the time of lesion formation. Inhibition of
      prostaglandins or TNF-alpha with ibuprofen or infliximab had no effect in this
      model. The C5a antagonists did not affect 3-NP-induced cell death when added
      directly to rat striatal neuronal cultures, indicating a secondary mechanism of
      action in vivo. Our findings demonstrate for the first time that complement
      activation in the brain, particularly C5a, is a key event in the pathogenesis of
      this disease model, and suggest a future role for inhibitors of C5a in the
      treatment of neurodegenerative diseases.

PMID- 16816117
TI  - A20, a modulator of smooth muscle cell proliferation and apoptosis, prevents and
      induces regression of neointimal hyperplasia.
AB  - A20 is a NF-kappaB-dependent gene that has dual anti-inflammatory and
      antiapoptotic functions in endothelial cells (EC). The function of A20 in smooth
      muscle cells (SMC) is unknown. We demonstrate that A20 is induced in SMC in
      response to inflammatory stimuli and serves an anti-inflammatory function via
      blockade of NF-kappaB and NF-kappaB-dependent proteins ICAM-1 and MCP-1. A20
      inhibits SMC proliferation via increased expression of cyclin-dependent kinase
      inhibitors p21waf1 and p27kip1. Surprisingly, A20 sensitizes SMC to cytokine- and
      Fas-mediated apoptosis through a novel NO-dependent mechanism. In vivo,
      adenoviral delivery of A20 to medial rat carotid artery SMC after balloon
      angioplasty prevents neointimal hyperplasia by blocking SMC proliferation and
      accelerating re-endothelialization, without causing apoptosis. However,
      expression of A20 in established neointimal lesions leads to their regression
      through increased apoptosis. This is the first demonstration that A20 exerts two
      levels of control of vascular remodeling and healing. A20 prevents neointimal
      hyperplasia through combined anti-inflammatory and antiproliferative functions in
      medial SMC. If SMC evade this first barrier and neointima is formed, A20 has a
      therapeutic potential by uniquely sensitizing neointimal SMC to apoptosis. A20
      based therapies hold promise for the prevention and treatment of neointimal
      disease.

PMID- 16816118
TI  - Peroxynitrite induces Alzheimer-like tau modifications and accumulation in rat
      brain and its underlying mechanisms.
AB  - To investigate the upstream effector that led to tau hyperphosphorylation,
      nitration, and accumulation as seen in Alzheimer's disease brain, and the
      underlying mechanisms, we bilaterally injected SIN-1, a recognized peroxynitrite
      donor, into the hippocampus of rat brain. We observed that the level of nitrated
      and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h after
      drug administration, and these alterations were prevented by preinjection of uric
      acid, a natural scavenger of peroxynitrite. Concomitantly, we detected a
      significant activation in glycogen synthase kinase-3beta (GSK-3beta) and p38
      MAPKs, including p38alpha, p38beta, and p38delta, but no obvious change was
      measured in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK).
      Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus,
      in which the activity of 20S proteasome was significantly arrested in SIN-1
      injected rats. Further studies demonstrated that the hyperphosphorylated tau was
      degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau
      with an unorderly secondary structure became more resistant to the proteolysis.
      These results provide the first in vivo evidence showing that peroxynitrite
      simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and
      that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the
      inhibition of proteasome activity are respectively responsible for the
      peroxynitrite-induced tau hyperphosphorylation and accumulation. Our findings
      reveal a common upstream stimulator and a potential therapeutic target for
      Alzheimer-like neurodegeneration.

PMID- 16816119
TI  - Calpain-2 regulation of VEGF-mediated angiogenesis.
AB  - Angiogenesis is a complex process involving endothelial cell migration,
      proliferation, and differentiation as well as tube formation. These processes are
      stimulated by a variety of growth factors such as vascular endothelial growth
      factor (VEGF). VEGF-induced cytoskeletal reorganization plays a crucial role in
      the angiogenic processes. In the present study, we evaluated the role of calpain
      in VEGF-induced angiogenesis in vitro and in vivo. Human pulmonary microvascular
      endothelial cells (PMEC) were incubated with VEGF (10-60 ng/ml) for 2-24 h, after
      which we measured calpain activities, protein contents of the calpain subunits
      and of calpastatin, endothelial monolayer wound repair, tube formation, and actin
      cytoskeleton changes. Incubation of PMEC with VEGF resulted in dose- and time
      dependent increases in calpain activity and protein content of calpain-2. VEGF
      did not change the protein contents of calpain-1 and the small subunit or of
      calpastatin. Incubation of PMEC with a VEGF receptor blocker prevented the VEGF
      induced increase in calpain activity. Inhibition of calpain activity by siRNA
      directed against calpain-2 and by overexpression of calpastatin prevented VEGF
      induced increases in actin stress fibers in endothelial cells and angiogenesis.
      Overexpression of calpastatin also inhibits vessel formation in subcutaneous
      (s.c.) matrigel plugs in mice. These results indicate that calpain mediates VEGF
      induced angiogenic effects by modulating actin cytoskeletal organization.

PMID- 16816120
TI  - Tau associates with actin in differentiating PC12 cells.
AB  - The microtubule-associated protein tau may be involved in cell morphogenesis and
      axonal maintenance. In addition to microtubules, tau has been shown to interact
      with actin in vitro. In the present study interaction of tau and actin was
      investigated in PC12 cells. No interaction between tau and actin was observed
      without NGF treatment. Under NGF stimulation, tau distributed at ends of cellular
      extensions, where it associated with actin in a microtubule-independent manner. F
      actin disruption revealed that relocalization and assembly of F-actin at the ends
      of cellular extensions were necessary for NGF-induced tau reorganization and
      association with actin. A truncated tau-GFP (tau(1-186)-GFP, N-terminal of tau)
      did not associate with actin. However, tau23(174-352)-GFP (carboxyl-terminal of
      Tau23) did associate with actin and the requirement for NGF was lost.
      Nevertheless, NGF boosted tau23(174-352)-GFP interaction with actin and promoted
      colocalization at the ends of cellular extensions. This suggests that the C
      terminal of tau is required for associating with actin and the tau N-terminal may
      play a regulatory role in this process. A possible role for tau-actin interaction
      in neurite outgrowth is postulated.

PMID- 16816121
TI  - Functional interaction of VEGF-C and VEGF-D with neuropilin receptors.
AB  - Lymphatic vascular development is regulated by vascular endothelial growth factor
      receptor-3 (VEGFR-3), which is activated by its ligands VEGF-C and VEGF-D.
      Neuropilin-2 (NP2), known to be involved in neuronal development, has also been
      implicated to play a role in lymphangiogenesis. We aimed to elucidate the
      mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in
      vitro binding studies we found that both VEGF-C and VEGF-D interact with NP2,
      VEGF-C in a heparin-independent and VEGF-D in a heparin-dependent manner. We also
      mapped the domains of VEGF-C and NP2 required for their binding. The functional
      importance of the interaction of NP2 with the lymphangiogenic growth factors was
      demonstrated by cointernalization of NP2 along with VEGFR-3 in endocytic vesicles
      of lymphatic endothelial cells upon stimulation with VEGF-C or VEGF-D. NP2 also
      interacted with VEGFR-3 in coprecipitation studies. Our results show that NP2 is
      directly involved in an active signaling complex with the key regulators of
      lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the
      development of the lymphatic vasculature.

PMID- 16816122
TI  - Selectively increased oxidative modifications mapped to detergent-insoluble forms
      of Abeta and beta-III tubulin in Alzheimer's disease.
AB  - Deleterious post-translational modifications (PTMs) to the neuronal cytoskeleton
      are a proposed mechanistic link between accumulation of amyloid (A) beta peptides
      and subsequent abnormalities of tau and neurodegeneration in Alzheimer's disease
      (AD). Here we tested the hypothesis that PTMs on neuronal tubulins selectively
      accumulate in a pathological protein fraction in AD. We used new software, P-MOD,
      to identify comprehensively and map PTMs using mass spectral data from soluble
      (normal) and detergent-insoluble (pathological) protein fractions from AD, as
      well as total extracts from controls, for selected proteins: Abeta, tau,
      apolipoprotein (apo) E, glial fibrillary acidic protein (GFAP), alpha-III
      tubulin, and beta-III tubulin. Our results confirmed direct observations of
      others by identifying methionine (M) sulfoxides at Abeta position 35 and numerous
      sites of tau phosphorylation in detergent-insoluble protein from AD, while no
      PTMs were enriched on primarily astrocyte-derived apoE or GFAP in this fraction.
      P-MOD mapped several abundant M sulfoxides to neuron-enriched beta-III tubulin
      but not its heterodimeric partner, neuron-enriched alpha-III tubulin, a result
      confirmed by selective suppression of CNBr-mediated cleavage of beta-III tubulin.
      These findings are the first comprehensive assessment of PTMs in AD and point to
      oxidative modification of beta-III tubulin as a potential contributor to the
      neuronal cytoskeletal disruption that is characteristic of AD.

PMID- 16816123
TI  - Effects of experimental type 1 diabetes and exercise training on angiogenic gene
      expression and capillarization in skeletal muscle.
AB  - Diabetes alters microvascular structure and function and is a major risk factor
      for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis
      and reduced VEGF-A expression have been observed, whereas in healthy muscle
      exercise is known to have opposite effects. We studied the effects of type 1
      diabetes and combined exercise training on angiogenic mRNA expression and
      capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses
      showed that diabetes altered the expression of several genes involved in
      angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1,
      VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospondin
      1 and retinoblastoma like-2 were increased. Exercise training alleviated some of
      these changes, but could not completely restore them. VEGF-A protein content was
      also reduced in diabetic muscles. In line with the reduced levels of VEGF-A and
      other angiogenic factors, and increased levels of angiogenesis inhibitors,
      capillary-to-muscle fiber ratio was lower in diabetic mice compared to healthy
      controls. Exercise training could not restore capillarization in diabetic mice.
      In conclusion, these data illustrate that type 1 diabetes is associated with
      reduced skeletal muscle capillarization and the dysregulation of complex
      angiogenesis pathways.

PMID- 16816124
TI  - The future of interdisciplinary research and training: how to conquer the silo
      guardians.
AB  - We have entered a new era in biomedical research in which large interdisciplinary
      teams are being established to answer important scientific questions. Scientists
      of multidisciplinary backgrounds within universities are combining forces and
      inter-institutional consortia that include alliances between academia and
      industry are springing up around the country to generate breakthrough advances. A
      number of driving forces are at work to establish these collaborative research
      approaches. By contrast, there also are barriers to be surmounted by institutions
      with silo mentalities for effective partnerships to be established. In order for
      this new era of research to reach maximal effectiveness, new approaches to
      education of the young and retraining of established administrators and
      scientists must take place. These issues were explored thoroughly at the 2006
      annual meeting of the Association of Anatomy, Cell Biology and Neurobiology
      Chairpersons (AACBNC) that was held in Aruba from January 18 to 21. The theme of
      this historic meeting was the Future of Interdisciplinary Research and Training:
      Breaking Down the Barriers. In this introductory article, we discuss the
      formation of a trendsetting Institute of Biomedical Sciences and Technology, the
      concept of the AACBNC meeting, and the influence of the Institute on the content
      of the meeting. The proceedings of this meeting, including Nobel Laureate Papers
      and Nobel Round-Table Discussions on the future of interdisciplinary research and
      training, are contained in this special issue of Experimental Biology and
      Medicine, a journal dedicated to the publication of multidisciplinary and
      interdisciplinary research in the biomedical sciences.

PMID- 16816125
TI  - Preparing K-12 students for the new interdisciplinary world of science.
AB  - The increasing importance of interdisciplinary science brings with it the need to
      consider what impact this has on the educational process. Such considerations
      extend even to the earliest educational years of K-12, and also exhibit a strong
      overlap with many issues involved in improving science education across the
      board. I will offer some general remarks, followed by a focus on three
      educational objectives of importance to interdisciplinary science as well as to
      improved science education as a whole. I will close with a brief discussion of
      the challenges involved in implementing such ideas in the educational system.

PMID- 16816126
TI  - Intracellular protein degradation: from a vague idea thru the lysosome and the
      ubiquitin-proteasome system and onto human diseases and drug targeting.
AB  - Between the 1950s and 1980s, scientists were focusing mostly on how the genetic
      code is transcribed to RNA and translated to proteins, but how proteins are
      degraded has remained a neglected research area. With the discovery of the
      lysosome by Christian de Duve it was assumed that cellular proteins are degraded
      within this organelle. Yet, several independent lines of experimental evidence
      strongly suggested that intracellular proteolysis is largely non-lysosomal, but
      the mechanisms involved remained obscure. The discovery of the
      ubiquitinproteasome system resolved the enigma. We now recognize that degradation
      of intracellular proteins is involved in regulation of a broad array of cellular
      processes, such as cell cycle and division, regulation of transcription factors,
      and assurance of the cellular quality control. Not surprisingly, aberrations in
      the system have been implicated in the pathogenesis of human disease, such as
      malignancies and neurodegenerative disorders, which led subsequently to an
      increasing effort to develop mechanism-based drugs.

PMID- 16816127
TI  - Agrienergy (agriculture/energy): what does the future hold?

PMID- 16816128
TI  - Nobel round-table discussion #1: the future of interdisciplinary research and
      training.

PMID- 16816129
TI  - Nobel round-table discussion #2: conflicts of interest, scientific misconduct,
      fair sharing, and intellectual property in an interdisciplinary/inter
      institutional consortium.

PMID- 16816130
TI  - A tale of two speeds: challenges for research universities.
AB  - This manuscript represents a presentation to the Annual Conference of the
      Association of Anatomy, Cell Biology and Neurobiology Chairpersons. The author is
      responding to the question, "How can university administrations nurture both
      interdisciplinary and inter-institutional collaboration and cooperation?" The
      presentation makes the point that university administrators must be cognizant of
      the changing dynamics of interdisciplinary and inter-institutional collaboration
      and cooperation due to the speed of the Internet and the speed of travel today.
      Those institutional leaders, and their universities, that recognize that the
      world has become flat will flourish, while those locked in a silo mentality will
      perish.

PMID- 16816131
TI  - Industry's challenge to academia: changing the bench to bedside paradigm.
AB  - The need for interdisciplinary collaboration is arising as a result of
      accelerating advances in basic science, including massive research and
      development funding by both government and industry, which has spurred the so
      called "nanotechnology revolution" and developments at the intersection of the
      life and physical sciences, increasing emphasis by federal research funding
      agencies on interdisciplinary and inter-institutional research and by market
      influences. A number of barriers presently limit the interaction between
      academics and industry, including the typically very time-consuming and slow pace
      of technology transfer, which is compounded in the case of interdisciplinary and
      inter-institutional licensing, as well as the natural, and understandable,
      antipathies that exist between academia and industry as a result of their
      differing missions and approaches to scientific discovery. Moreover, if
      mechanisms are not in place at the outset of an inter-university collaboration,
      then the transition of inventions to clinical applications can be fraught with
      additional complexities and barriers. Policies suggested by the National
      Nanotechnology Initiative offer a number of ideas for overcoming barriers to
      multidisciplinary and inter-institutional research and illustrate some of the
      ways in which academia can structure partnerships with industry that will not
      only provide needed funding for multidisciplinary and inter-institutional
      biomedical research in an era of diminishing federal resources, but may permit
      academia, on the one hand, and industry, on the other, to benefit from the
      strengths provided by the other without compromising either academia's or
      industry's basic missions.

PMID- 16816132
TI  - Issues on research integrity: a perspective.
AB  - This paper discusses several key issues that are relevant to the integrity and
      success of the biomedical research enterprise. Attention to these issues will
      improve research outcomes and reduce negative consequences in research. Subjects
      addressed include normative practices in research; the importance of quality
      data; mentoring of young scientists; how to proceed when a member of the
      scientific community discovers misconduct or other breaches of integrity; and the
      level of harm to public confidence in research due to misconduct and lack of
      transparency in research findings.

PMID- 16816133
TI  - Complainant issues in research misconduct: the office of research integrity
      experience.
AB  - This paper discusses the experiences of the Office of Research Integrity (ORI)
      with issues involving complainants who make allegations of research misconduct.
      The paper describes the legal framework for complainant issues, the various roles
      of the complainant as the allegation of misconduct proceeds through the steps of
      investigation and resolution, how allegations of retaliation against the
      complainant are handled, the responsibilities of ORI and of the research
      institution where the alleged misconduct occurred, and ORI's experience with
      several cases of alleged retaliation. In each of these areas, the paper attempts
      to provide guidance to prospective complainants, research institutions, and other
      interested persons on effective ways to approach the various problems and
      concerns that arise, while maintaining a balance between the needs of the
      complainant, the accused, the research institution handling the allegation, and
      ORI.

PMID- 16816134
TI  - Retinoblastoma tumor suppressor: where cancer meets the cell cycle.
AB  - The retinoblastoma tumor suppressor gene, Rb, was the first tumor suppressor
      identified and plays a fundamental role in regulation of progression through the
      cell cycle. This review details facets of RB protein function in cell cycle
      control and focuses on specific questions that remain intensive areas of
      investigation.

PMID- 16816135
TI  - A variable cluster of ethylene response factor-like genes regulates metabolic and
      developmental acclimation responses to submergence in rice.
AB  - Submergence-1 (Sub1), a major quantitative trait locus affecting tolerance to
      complete submergence in lowland rice (Oryza sativa), contains two or three
      ethylene response factor (ERF)-like genes whose transcripts are regulated by
      submergence. In the submergence-intolerant japonica cultivar M202, this locus
      encodes two ERF genes, Sub1B and Sub1C. In the tolerant near-isogenic line
      containing the Sub1 locus from the indica FR13A, M202(Sub1), the locus
      additionally encodes the ERF gene Sub1A. During submergence, the tolerant
      M202(Sub1) displayed restrained leaf and internode elongation, chlorophyll
      degradation, and carbohydrate consumption, whereas the enzymatic activities of
      pyruvate decarboxylase and alcohol dehydrogenase were increased significantly
      compared with the intolerant M202. Transcript levels of genes associated with
      carbohydrate consumption, ethanolic fermentation, and cell expansion were
      distinctly regulated in the two lines. Sub1A and Sub1C transcript levels were
      shown to be upregulated by submergence and ethylene, with the Sub1C allele in
      M202 also upregulated by treatment with gibberellic acid (GA). These findings
      demonstrate that the Sub1 region haplotype determines ethylene- and GA-mediated
      metabolic and developmental responses to submergence through differential
      expression of Sub1A and Sub1C. Submergence tolerance in lowland rice is conferred
      by a specific allele variant of Sub1A that dampens ethylene production and GA
      responsiveness, causing quiescence in growth that correlates with the capacity
      for regrowth upon desubmergence.

PMID- 16816136
TI  - Arabidopsis LHT1 is a high-affinity transporter for cellular amino acid uptake in
      both root epidermis and leaf mesophyll.
AB  - Amino acid transport in plants is mediated by at least two large families of
      plasma membrane transporters. Arabidopsis thaliana, a nonmycorrhizal species, is
      able to grow on media containing amino acids as the sole nitrogen source.
      Arabidopsis amino acid permease (AAP) subfamily genes are preferentially
      expressed in the vascular tissue, suggesting roles in long-distance transport
      between organs. We show that the broad-specificity, high-affinity amino acid
      transporter LYSINE HISTIDINE TRANSPORTER1 (LHT1), an AAP homolog, is expressed in
      both the rhizodermis and mesophyll of Arabidopsis. Seedlings deficient in LHT1
      cannot use Glu or Asp as sole nitrogen sources because of the severe inhibition
      of amino acid uptake from the medium, and uptake of amino acids into mesophyll
      protoplasts is inhibited. Interestingly, lht1 mutants, which show growth defects
      on fertilized soil, can be rescued when LHT1 is reexpressed in green tissue.
      These findings are consistent with two major LHT1 functions: uptake in roots and
      supply of leaf mesophyll with xylem-derived amino acids. The capacity for amino
      acid uptake, and thus nitrogen use efficiency under limited inorganic N supply,
      is increased severalfold by LHT1 overexpression. These results suggest that LHT1
      overexpression may improve the N efficiency of plant growth under limiting
      nitrogen, and the mutant analyses may enhance our understanding of N cycling in
      plants.

PMID- 16816137
TI  - A chromoplast-specific carotenoid biosynthesis pathway is revealed by cloning of
      the tomato white-flower locus.
AB  - Carotenoids and their oxygenated derivatives xanthophylls play essential roles in
      the pigmentation of flowers and fruits. Wild-type tomato (Solanum lycopersicum)
      flowers are intensely yellow due to accumulation of the xanthophylls neoxanthin
      and violaxanthin. To study the regulation of xanthophyll biosynthesis, we
      analyzed the mutant white-flower (wf). It was found that the recessive wf
      phenotype is caused by mutations in a flower-specific beta-ring carotene
      hyroxylase gene (CrtR-b2). Two deletions and one exon-skipping mutation in
      different CrtR-b2 wf alleles abolish carotenoid biosynthesis in flowers but not
      leaves, where the homologous CrtR-b1 is constitutively expressed. A second beta
      carotene hydroxylase enzyme as well as flower- and fruit-specific geranylgeranyl
      diphosphate synthase, phytoene synthase, and lycopene beta-cyclase together
      define a carotenoid biosynthesis pathway active in chromoplasts only,
      underscoring the crucial role of gene duplication in specialized plant metabolic
      pathways. We hypothesize that this pathway in tomato was initially selected
      during evolution to enhance flower coloration and only later recruited to enhance
      fruit pigmentation. The elimination of beta-carotene hydroxylation in wf petals
      results in an 80% reduction in total carotenoid concentration, possibly caused by
      the inability of petals to store high concentrations of carotenoids other than
      xanthophylls and by degradation of beta-carotene, which accumulates as a result
      of the wf mutation but is not due to altered expression of genes in the
      biosynthetic pathway.

PMID- 16816138
TI  - Physiology of local renin-angiotensin systems.
AB  - Since the first identification of renin by Tigerstedt and Bergmann in 1898, the
      renin-angiotensin system (RAS) has been extensively studied. The current view of
      the system is characterized by an increased complexity, as evidenced by the
      discovery of new functional components and pathways of the RAS. In recent years,
      the pathophysiological implications of the system have been the main focus of
      attention, and inhibitors of the RAS such as angiotensin-converting enzyme (ACE)
      inhibitors and angiotensin (ANG) II receptor blockers have become important
      clinical tools in the treatment of cardiovascular and renal diseases such as
      hypertension, heart failure, and diabetic nephropathy. Nevertheless, the tissue
      RAS also plays an important role in mediating diverse physiological functions.
      These focus not only on the classical actions of ANG on the cardiovascular
      system, namely, the maintenance of cardiovascular homeostasis, but also on other
      functions. Recently, the research efforts studying these noncardiovascular
      effects of the RAS have intensified, and a large body of data are now available
      to support the existence of numerous organ-based RAS exerting diverse
      physiological effects. ANG II has direct effects at the cellular level and can
      influence, for example, cell growth and differentiation, but also may play a role
      as a mediator of apoptosis. These universal paracrine and autocrine actions may
      be important in many organ systems and can mediate important physiological
      stimuli. Transgenic overexpression and knock-out strategies of RAS genes in
      animals have also shown a central functional role of the RAS in prenatal
      development. Taken together, these findings may become increasingly important in
      the study of organ physiology but also for a fresh look at the implications of
      these findings for organ pathophysiology.

PMID- 16816139
TI  - Cholecystokinin and gastrin receptors.
AB  - Cholecystokinin and gastrin receptors (CCK1R and CCK2R) are G protein-coupled
      receptors that have been the subject of intensive research in the last 10 years
      with corresponding advances in the understanding of their functioning and
      physiology. In this review, we first describe general properties of the
      receptors, such as the different signaling pathways used to exert short- and long
      term effects and the structural data that explain their binding properties,
      activation, and regulation. We then focus on peripheral cholecystokinin receptors
      by describing their tissue distribution and physiological actions. Finally,
      pathophysiological peripheral actions of cholecystokinin receptors and their
      relevance in clinical disorders are reviewed.

PMID- 16816140
TI  - Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding
      cassette multidrug resistance proteins.
AB  - Multidrug Resistance Proteins (MRPs), together with the cystic fibrosis
      conductance regulator (CFTR/ABCC7) and the sulfonylurea receptors (SUR1/ABCC8 and
      SUR2/ABCC9) comprise the 13 members of the human "C" branch of the ATP binding
      cassette (ABC) superfamily. All C branch proteins share conserved structural
      features in their nucleotide binding domains (NBDs) that distinguish them from
      other ABC proteins. The MRPs can be further divided into two subfamilies "long"
      (MRP1, -2, -3, -6, and -7) and "short" (MRP4, -5, -8, -9, and -10). The short
      MRPs have a typical ABC transporter structure with two polytropic membrane
      spanning domains (MSDs) and two NBDs, while the long MRPs have an additional NH2
      terminal MSD. In vitro, the MRPs can collectively confer resistance to natural
      product drugs and their conjugated metabolites, platinum compounds, folate
      antimetabolites, nucleoside and nucleotide analogs, arsenical and antimonial
      oxyanions, peptide-based agents, and, under certain circumstances, alkylating
      agents. The MRPs are also primary active transporters of other structurally
      diverse compounds, including glutathione, glucuronide, and sulfate conjugates of
      a large number of xeno- and endobiotics. In vivo, several MRPs are major
      contributors to the distribution and elimination of a wide range of both
      anticancer and non-anticancer drugs and metabolites. In this review, we describe
      what is known of the structure of the MRPs and the mechanisms by which they
      recognize and transport their diverse substrates. We also summarize knowledge of
      their possible physiological functions and evidence that they may be involved in
      the clinical drug resistance of various forms of cancer.

PMID- 16816141
TI  - Adenosine and kidney function.
AB  - In this review we outline the unique effects of the autacoid adenosine in the
      kidney. Adenosine is present in the cytosol of renal cells and in the
      extracellular space of normoxic kidneys. Extracellular adenosine can derive from
      cellular adenosine release or extracellular breakdown of ATP, AMP, or cAMP. It is
      generated at enhanced rates when tubular NaCl reabsorption and thus transport
      work increase or when hypoxia is induced. Extracellular adenosine acts on
      adenosine receptor subtypes in the cell membranes to affect vascular and tubular
      functions. Adenosine lowers glomerular filtration rate (GFR) by constricting
      afferent arterioles, especially in superficial nephrons, and acts as a mediator
      of the tubuloglomerular feedback, i.e., a mechanism that coordinates GFR and
      tubular transport. In contrast, it leads to vasodilation in deep cortex and
      medulla. Moreover, adenosine tonically inhibits the renal release of renin and
      stimulates NaCl transport in the cortical proximal tubule but inhibits it in
      medullary segments including the medullary thick ascending limb. These
      differential effects of adenosine are subsequently analyzed in a more integrative
      way in the context of intrarenal metabolic regulation of kidney function, and
      potential pathophysiological consequences are outlined.

PMID- 16816142
TI  - Voltage-gated calcium channels and idiopathic generalized epilepsies.
AB  - The idiopathic generalized epilepsies encompass a class of epileptic seizure
      types that exhibit a polygenic and heritable etiology. Advances in molecular
      biology and genetics have implicated defects in certain types of voltage-gated
      calcium channels and their ancillary subunits as important players in this form
      of epilepsy. Both T-type and P/Q-type channels appear to mediate important
      contributions to seizure genesis, modulation of network activity, and genetic
      seizure susceptibility. Here, we provide a comprehensive overview of the roles of
      these channels and associated subunits in normal and pathological brain activity
      within the context of idiopathic generalized epilepsy.

PMID- 16816143
TI  - Nuclear lamins: laminopathies and their role in premature ageing.
AB  - It has been demonstrated that nuclear lamins are important proteins in
      maintaining cellular as well as nuclear integrity, and in maintaining chromatin
      organization in the nucleus. Moreover, there is growing evidence that lamins play
      a prominent role in transcriptional control. The family of laminopathies is a
      fast-growing group of diseases caused by abnormalities in the structure or
      processing of the lamin A/C (LMNA) gene. Mutations or incorrect processing cause
      more than a dozen different inherited diseases, ranging from striated muscular
      diseases, via fat- and peripheral nerve cell diseases, to progeria. This broad
      spectrum of diseases can only be explained if the responsible A-type lamin
      proteins perform multiple functions in normal cells. This review gives an
      overview of current knowledge on lamin structure and function and all known
      diseases associated with LMNA abnormalities. Based on the knowledge of the
      different functions of A-type lamins and associated proteins, explanations for
      the observed phenotypes are postulated. It is concluded that lamins seem to be
      key players in, among others, controlling the process of cellular ageing, since
      disturbance in lamin protein structure gives rise to several forms of premature
      ageing.

PMID- 16816144
TI  - Astrocyte control of synaptic transmission and neurovascular coupling.
AB  - From a structural perspective, the predominant glial cell of the central nervous
      system, the astrocyte, is positioned to regulate synaptic transmission and
      neurovascular coupling: the processes of one astrocyte contact tens of thousands
      of synapses, while other processes of the same cell form endfeet on capillaries
      and arterioles. The application of subcellular imaging of Ca2+ signaling to
      astrocytes now provides functional data to support this structural notion.
      Astrocytes express receptors for many neurotransmitters, and their activation
      leads to oscillations in internal Ca2+. These oscillations induce the
      accumulation of arachidonic acid and the release of the chemical transmitters
      glutamate, d-serine, and ATP. Ca2+ oscillations in astrocytic endfeet can control
      cerebral microcirculation through the arachidonic acid metabolites prostaglandin
      E2 and epoxyeicosatrienoic acids that induce arteriole dilation, and 20-HETE that
      induces arteriole constriction. In addition to actions on the vasculature, the
      release of chemical transmitters from astrocytes regulates neuronal function.
      Astrocyte-derived glutamate, which preferentially acts on extrasynaptic
      receptors, can promote neuronal synchrony, enhance neuronal excitability, and
      modulate synaptic transmission. Astrocyte-derived d-serine, by acting on the
      glycine-binding site of the N-methyl-d-aspartate receptor, can modulate synaptic
      plasticity. Astrocyte-derived ATP, which is hydrolyzed to adenosine in the
      extracellular space, has inhibitory actions and mediates synaptic cross-talk
      underlying heterosynaptic depression. Now that we appreciate this range of
      actions of astrocytic signaling, some of the immediate challenges are to
      determine how the astrocyte regulates neuronal integration and how both
      excitatory (glutamate) and inhibitory signals (adenosine) provided by the same
      glial cell act in concert to regulate neuronal function.

PMID- 16816145
TI  - Spike timing-dependent plasticity: from synapse to perception.
AB  - Information in the nervous system may be carried by both the rate and timing of
      neuronal spikes. Recent findings of spike timing-dependent plasticity (STDP) have
      fueled the interest in the potential roles of spike timing in processing and
      storage of information in neural circuits. Induction of long-term potentiation
      (LTP) and long-term depression (LTD) in a variety of in vitro and in vivo systems
      has been shown to depend on the temporal order of pre- and postsynaptic spiking.
      Spike timing-dependent modification of neuronal excitability and dendritic
      integration was also observed. Such STDP at the synaptic and cellular level is
      likely to play important roles in activity-induced functional changes in neuronal
      receptive fields and human perception.

PMID- 16816146
TI  - Expression of angiogenic growth factors by uterine natural killer cells during
      early pregnancy.
AB  - Remodeling of uterine spiral arteries is critical for the continuation of a
      successful pregnancy. Uterine natural killer (uNK) cells are the predominant
      leukocyte population in the early pregnant decidua, and a role for these cells in
      spiral artery remodeling in pregnancy has been suggested. Angiogenic growth
      factors were measured in isolated uNK and total (unseparated) decidual cells (8
      10 or 12-14 weeks gestation, n=5 each gestational age) after culture for 48 h.
      Angiopoietin (Ang)1, placental growth factor, transforming growth factor-beta1
      (TGF-beta1), and vascular endothelial growth factor (VEGF)-C were measured by
      enzyme-linked immunosorbent assay. Angiogenin, Ang2, fibroblast growth factor
      basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor
      (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a
      FASTQuant angiogenic growth factor multiplex protein assay. Levels of Ang2, ICAM
      1, and KGF, secreted by the total decidual fraction, decreased with increasing
      gestational age. uNK levels of Ang2 and VEGF-C also decreased with increasing
      gestational age. At 8-10 weeks gestation, there was no difference in the level of
      Ang1, Ang2, TGF-beta1, and VEGF-C secreted by uNK cells and the total decidual
      fraction. At 12-14 weeks, uNK cells secreted significantly lower levels of VEGF-C
      than the total decidual fraction. Early pregnancy decidua is a major source of
      angiogenic growth factors whose levels decrease with increasing gestational age,
      suggesting that they may play a role in spiral artery remodeling. uNK cells
      appear to be a prominent source of Ang1, Ang2, TGF-beta1, and VEGF-C within the
      placental bed.

PMID- 16816147
TI  - Differential infection of mononuclear phagocytes by Francisella tularensis: role
      of the macrophage mannose receptor.
AB  - Francisella tularensis (Ft) is a Gram-negative bacterium and the causative agent
      of tularemia. It is well established that this organism replicates inside
      macrophages, but we are only beginning to understand this interface at the
      molecular level. Herein, we compared directly the ability of Ft subspecies
      holarctica live-vaccine strain to infect freshly isolated human peripheral blood
      monocytes, monocyte-derived macrophages (MDM), and cells of the murine macrophage
      cell line J774A.1 (J774). We now show that unopsonized bacteria infected human
      MDM fivefold more efficiently than monocytes or J774 cells in standard media.
      Moreover, enhanced infection of MDM was mediated, in part, by the macrophage
      mannose receptor (MR). Forming Ft phagosomes accumulated MR, and infection was
      inhibited by MR-blocking antibody or soluble mannan but not by the dectin-1
      ligand laminarin. Up-regulation of MR in MDM (by exposure to interleukin-4)
      increased Ft phagocytosis, as did expression of MR in J774 cells. Conversely,
      opsonized Ft were ingested readily by monocytes and MDM. Medium supplementation
      with 2.5% fresh autologous serum was sufficient to confer opsonophagocytosis and
      CD11b accumulated in the membrane at sites of Ft engulfment. Infection of
      monocytes by opsonized Ft was nearly ablated by complement receptor 3 (CR3)
      blockade. Conversely, MDM used MR and CD11b/CD18 to ingest opsonized organisms.
      Altogether, our data demonstrate differential infection of mononuclear phagocytes
      by Ft and define distinct roles for MR and CR3 in phagocytosis.

PMID- 16816148
TI  - The role of the medial collateral ligament and posteromedial capsule in
      controlling knee laxity.
AB  - BACKGROUND: The medial aspect of the knee has a complex capsular structure; the
      biomechanical roles of specific structures are not well understood. HYPOTHESIS:
      The 3 strong stabilizing structures, the superficial and deep medial collateral
      ligaments and the posteromedial capsule, make distinct contributions to
      controlling tibiofemoral laxity. STUDY DESIGN: Controlled laboratory study.
      METHODS: Changes in knee laxity under anterior-posterior drawer, valgus, and
      internal-external rotation loads were found by sequential cutting in 18 cadaveric
      knees. Three cutting sequences allowed the roles of the 3 structures to be seen
      in isolation and in combination. Some force contributions were also calculated.
      RESULTS: The posteromedial capsule controlled valgus, internal rotation, and
      posterior drawer in extension, resisting 42% of a 150-N drawer force when the
      tibia was in internal rotation. The superficial collateral ligament controlled
      valgus at all angles and was dominant from 30 degrees to 90 degrees of flexion,
      plus internal rotation in flexion. The deep collateral ligament controlled tibial
      anterior drawer of the flexed and externally rotated knee and was a secondary
      restraint to valgus. CONCLUSION: Distinct roles in controlling tibiofemoral
      laxity have been found for these structures that vary according to knee flexion
      and tibial rotation. CLINICAL RELEVANCE: The restraining functions demonstrated
      provide new information about knee stabilization, which may allow better
      evaluation of structural damage at the medial aspect of the knee.

PMID- 16816149
TI  - Pronociceptive and antinociceptive neuromediators in patellar tendinopathy.
AB  - BACKGROUND: The occurrence of nerve ingrowth and its relation to chronic tendon
      pain (tendinopathy) are still largely unknown. In healthy tendons, the
      innervation is confined to the paratenon, whereas the tendon proper is devoid of
      nerve fibers. In this study on the pathogenesis of tendinopathy, the authors
      examined sensory and sympathetic nerve fiber occurrence in the patellar tendon.
      HYPOTHESIS: Nerve ingrowth and altered expression of sensory and sympathetic
      neuromediators play a major role in the pathophysiology of pain in patellar
      tendinopathy. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS:
      Biopsies from the patellar tendon in patients with patellar tendinopathy (n = 10)
      were compared with biopsies from a control group (n = 10) without any previous or
      current knee symptoms compatible with patellar tendinopathy. The biopsies were
      stained immunohistochemically for sensory and autonomic nerve markers. The
      biopsies from the 2 groups were compared using subjective and semiquantitative
      methods. RESULTS: Chronic painful patellar tendons exhibited increased occurrence
      of sprouting nonvascular sensory, substance P-positive nerve fibers and a
      decreased occurrence of vascular sympathetic nerve fibers, positive to tyroxin
      hydroxylase, a marker for noradrenaline. CONCLUSION: The altered sensory
      sympathetic innervation suggests a role in the pathophysiology of tendinopathy.
      Ingrowth of sprouting substance P fibers presumably reflects a nociceptive and
      maybe a proliferative role, possibly as reactions to repeated microtraumata,
      whereas the decreased occurrence of tyroxin hydroxylase may represent a reduced
      antinociceptive role. These findings could be used to develop targeted
      pharmacotherapy for the specific treatment of tendinopathy.

PMID- 16816150
TI  - Translation and validation of the Dutch version of the International Knee
      Documentation Committee Subjective Knee Form.
AB  - BACKGROUND: For knee-related surgery, there is a great demand for internationally
      useable subjective scoring systems. Before such measurements can be used, they
      should be translated and validated for the population they are used on. For the
      Dutch population, only the Western Ontario and McMaster Universities
      Osteoarthritis Index and Oxford 12 Questionnaire have been validated. However,
      these scores can only be used regarding osteoarthritis of the knee. In 2001, the
      International Knee Documentation Committee presented the Subjective Knee Form,
      which is a knee-specific rather than a disease-specific questionnaire. STUDY
      DESIGN: Cohort study (diagnosis/symptom prevalence); Level of evidence, 2.
      METHODS: The authors describe the translation procedure and validation of the
      Dutch Subjective Knee Form. After a forward-backward translation protocol, the
      reliability, validity, and content validity were tested. The responses of 145
      consecutive knee patients on 2 questionnaires containing the Short Form-36,
      Western Ontario and McMaster Universities Osteoarthritis Index, Oxford 12
      Questionnaire score, a visual analog scale, and the Dutch International Knee
      Documentation Committee Subjective Knee Form were used. Reliability was tested by
      measuring the test-retest reliability and internal consistency. Validity was
      tested by correlating the questionnaire to the other outcome measurements, and
      content validity was tested by measuring the floor and ceiling effects. RESULTS:
      The reliability proved excellent with an intraclass coefficient of 0.96 for test
      retest. Internal consistency was strong (Cronbach alpha, .92). The construct,
      convergent, and divergent validities were good. The content validity was good; no
      floor or ceiling effect occurred. CONCLUSION: The validation procedure shows that
      the Dutch International Knee Documentation Committee Subjective Knee Form is an
      excellent evaluation instrument for Dutch patients with knee-related injuries.

PMID- 16816151
TI  - The "value added" of neurocognitive testing after sports-related concussion.
AB  - BACKGROUND: Neurocognitive testing has been endorsed as a "cornerstone" of
      concussion management by recent Vienna and Prague meetings of the Concussion in
      Sport Group. Neurocognitive testing is important given the potential
      unreliability of athlete self-report after injury. Relying only on athletes'
      reports of symptoms may result in premature return of athletes to contact sport,
      potentially exposing them to additional injury. HYPOTHESIS: Use of computer-based
      neurocognitive testing results in an increased capacity to detect postconcussive
      abnormalities after injury. STUDY DESIGN: Case control study; Level of evidence,
      3. METHODS: High school and college athletes with a diagnosed concussion were
      tested 2 days after injury. Postinjury neurocognitive performance (Immediate
      Postconcussion Assessment and Cognitive Testing) and symptom (postconcussion
      symptom) scores were compared with preinjury (baseline) scores and with those of
      an age- and education-matched noninjured athlete control group. "Abnormal" test
      performance was determined statistically with Reliable Change Index scores.
      RESULTS: Sixty-four percent of concussed athletes reported a significant increase
      in symptoms, as judged by postconcussion symptom scores, compared with preinjury
      baseline at 2 days after injury. Eighty-three percent of the concussed sample
      demonstrated significantly poorer neurocognitive test results relative to their
      own baseline performance. The addition of neurocognitive testing resulted in a
      net increase in sensitivity of 19%. Ninety-three percent of the sample had either
      abnormal neurocognitive test results or a significant increase in symptoms,
      relative to their own baseline; 30% of a control group demonstrated either
      abnormalities in neurocognitive testing or elevated symptoms, as judged by
      postconcussion symptom scores. For the concussed group, use of symptom and
      neurocognitive test results resulted in an increased yield of 29% overreliance on
      symptoms alone. In contrast, 0% of the control group had both symptoms and
      abnormal neurocognitive testing. CONCLUSION: Reliance on patients' self-reported
      symptoms after concussion is likely to result in underdiagnosis of concussion and
      may result in premature return to play. Neurocognitive testing increases
      diagnostic accuracy when used in conjunction with self-reported symptoms.

PMID- 16816152
TI  - Catastrophic cervical spine injuries in high school and college football players.
AB  - BACKGROUND: Catastrophic cervical spine injuries in football are rare but tragic
      events. PURPOSE: To update the incidence of catastrophic cervical injuries in
      scholastic football players and identify new injury patterns. STUDY DESIGN:
      Descriptive epidemiology study. METHODS: The authors retrospectively reviewed 196
      incidents of catastrophic high school and collegiate football injuries reported
      to the National Center for Catastrophic Sports Injury Research during 13 academic
      years (September 1989 through June 2002). RESULTS: There were 15.08 direct
      catastrophic cervical spine injuries in scholastic football participants per
      year, an incidence of 1.10 and 4.72 injuries per 100 000 high school and 100 000
      college participants, respectively. Seventy-six athletes had quadriplegia (5.85
      per year), 0.50 per 100 000 high school players and 0.82 per 100 000 college
      players. Spear tackling by players on defense continued to be the predominant
      mechanism of injury causing quadriplegia. Five athletes had a Brown-Sequard-like
      syndrome; only 1 made a full recovery. One athlete with Brown-Sequard-like
      syndrome and permanent neurologic symptoms reported a cervical cord neurapraxia
      event before the study period. Forty-three athletes (3.31 per year) had diagnosed
      cervical cord neurapraxia. In addition to hyperflexion and hyperextension
      injuries, axial forces were found to cause cervical cord neurapraxia. Sixteen of
      the 43 athletes returned to football after a cervical cord neurapraxia episode,
      and none of the 16 suffered a permanent quadriplegic event. Nine athletes
      sustained an isolated injury at the C1 or C2 level, and 7 sustained a combined
      injury at the C1, or C2 level and at a subaxial level. CONCLUSION: The total
      number of quadriplegic events for high school and college football players is
      approximately 6 per year, with a higher incidence at the college level. Cervical
      cord neurapraxia can be caused by hyperflexion, hyperextension, and axial
      compression forces. Upper level cervical injuries involving the atlas and axis
      can occur in football players and may be associated with noncontiguous subaxial
      injuries.

PMID- 16816154
TI  - Serological responses of adult dogs to revaccination against distemper,
      parvovirus and rabies.
AB  - Serum antibody titres to canine distemper virus (CDV), canine parvovirus (CPV)
      and rabies were measured in dogs that had not been revaccinated annually and
      compared with the titres in a control group of regularly vaccinated animals; 83
      per cent (171 of 207) of the dogs vaccinated against CDV one or more years
      earlier had serum neutralising antibody titres equal to or greater than 16; 64
      per cent (136 of 213) of the dogs vaccinated against CPV one or more years
      earlier had haemagglutination inhibiting titres equal to or greater than 80; and
      59 per cent (46 of 78) of the dogs vaccinated against rabies two or more years
      earlier had serum neutralising antibody titres equal to or greater than 0.5
      iu/ml. Three weeks after a single booster vaccination the dogs' antibody titres
      against CDV had increased above the threshold level in 94 per cent of the dogs,
      against CPV in 68 per cent, and against rabies in 100 per cent.

PMID- 16816155
TI  - Idiopathic immune-mediated polysynovitis in three horses.
AB  - This paper describes the clinical, laboratory and histological findings in three
      horses with immune-mediated polysynovitis; they had lost weight, suffered
      intermittent fever, were lethargic and stiff, and had effusions in several
      joints. Laboratory abnormalities included anaemia, leucocytosis,
      hyperfibrinogenaemia and hyperglobulinaemia. The diagnosis was based on the
      presence of a suppurative, non-septic inflammation in at least two different
      joints in each of the horses and the presence of immunoglobulins in the synovial
      membrane of one of them. The horses were treated with a combination of
      dexamethasone and azathioprine, and responded well to the initial treatment.
      Twenty months after its last re-evaluation, the first horse was being maintained
      on azathioprine because similar clinical signs had recurred after the cytotoxic
      drug was discontinued; the second horse was finishing a tapering course of
      prednisolone 15 months after its first examination, and the third horse was
      euthanased five months after it was first examined as a result of an unrelated
      injury.

PMID- 16816156
TI  - Diazinon toxicity in sheep and cattle arising from the misuse of unlicensed and
      out-of-date products.
AB  - Two incidents involving the misuse of unlabelled or out-of-date diazinon products
      are described. In the first incident, 81 of a group of 210 five-month-old lambs
      died within 12 hours of being dipped with the contents of a partly used tin of 15
      year-old sheep dip. Analysis showed that the diazinon had decomposed by
      hydrolysis into a range of breakdown products, including
      tetraethyldithiopyrophosphate (sulfotepp) and monothiono-tetraethylpyrophosphate
      (monothiono-TEPP), which are much more toxic to mammals than diazinon. In the
      second incident, four yearling bulls were affected within 48 hours of being
      treated with a liquid that the farmer believed to be a lice treatment but was
      actually old diazinon sheep dip. Three of the bulls recovered but one died four
      days after the treatment. Analysis of the dip confirmed the presence of diazinon
      but in this incident no breakdown products were detected.

PMID- 16816157
TI  - Efficacy of systemic cefquinome and erythromycin against digital dermatitis in
      cattle.

PMID- 16816158
TI  - Small intestinal volvulus in a captive Steller sea lion (Eumetopias jubatus).

PMID- 16816159
TI  - Corynebacterium pseudotuberculosis infection in highland alpacas (Lama pacos) in
      Peru.

PMID- 16816160
TI  - Retrocaval ureter in a cat.

PMID- 16816161
TI  - Vets and international disaster management.

PMID- 16816163
TI  - Euthanasia of exotic pigs.

PMID- 16816164
TI  - Euthanasia of exotic pigs.

PMID- 16816165
TI  - Veterinary nurses and acupuncture.

PMID- 16816167
TI  - Prognostic significance of mucins in colorectal cancer with different DNA
      mismatch-repair status.
AB  - BACKGROUND: Expression of mucin antigen MUC1 and down regulation of MUC2 are
      associated with adverse prognosis in colorectal cancer (CRC), but their
      prognostic significance with respect to differing DNA mis- match repair (MMR)
      status is poorly understood. OBJECTIVE: To determine the prognostic significance
      of MUC1 and MUC2 in CRC with different MMR statuses. METHODS: Using the tissue
      microarray (TMA) technique, a series of 1420 unselected, non-consecutive CRC
      resections was subdivided into three groups: (1) MMR-proficient; (2) MLH1
      negative; and (3) presumed hereditary non-polyposis colon cancer (HNPCC).
      Immunohistochemical analysis of MUC1 and MUC2 expression (>0%) and loss (0%) was
      performed, and the results were correlated with clinicopathological parameters.
      RESULTS: In MMR-proficient CRC, MUC1 expression was more frequently found in
      tumours with higher tumour stage (p=0.004) and higher tumour grade (p=0.041) and
      loss of MUC2 was associated with higher tumour stage (p=0.028), node stage
      (p=0.001), presence of vascular invasion (p=0.028) and worse survival (p=0.034).
      In MLH1-negative CRC, MUC2 loss was associated with the presence of lymph node
      metastasis (p=0.028) and worse survival (p=0.015), but there was no association
      between MUC1 expression and clinicopathological features. In presumed HNPCC, MUC1
      expression and MUC2 loss were not associated with clinicopathological parameters.
      CONCLUSIONS: Mucins have a prognostic significance in sporadic CRC, but not in
      hereditary CRC. Loss of MUC2 is an adverse prognostic factor in MMR-proficient
      and MLH1-negative CRC, whereas MUC1 expression is associated with tumour
      progression in MMR-proficient CRC only.

PMID- 16816169
TI  - Improved clonality assessment in germinal centre/post-germinal centre non
      Hodgkin's lymphomas with high rates of somatic hypermutation.
AB  - BACKGROUND: PCR detects clonal rearrangements of the Ig gene in
      lymphoproliferative disorders. False negativity occurs in germinal centre/post
      germinal centre lymphomas (GC/PGCLs) as they display a high rate of somatic
      hypermutation (SHM), which causes primer mismatching when detecting Ig
      rearrangements by PCR. AIMS: To investigate the degree of SHM in a group of
      GC/PGCLs and assess the rate of false negativity when using BIOMED-2 PCR when
      compared with previously published strategies. METHODS: DNA was isolated from
      snap-frozen tissue from 49 patients with GC/PGCL (23 diffuse large B cell
      lymphomas (DLBCLs), 26 follicular lymphomas (FLs)) and PCR-amplified for complete
      (VDJH), incomplete (DJH) and Ig kappa/lambda rearrangements using the BIOMED-2
      protocols, and compared with previously published methods using consensus
      primers. Germinal centre phenotype was defined by immunohistochemistry based on
      CD10, Bcl-6 and MUM-1. RESULTS: Clonality detection by amplifying Ig
      rearrangements using BIOMED-2 family-specific primers was considerably higher
      than that found using consensus primers (74% DLBCL and 96% FL vs 69% DLBCL and
      73% FL). Addition of BIOMED-2 DJH rearrangements increased detection of clonality
      by 22% in DLBCL. SHM was present in VDJH rearrangements from all patients with
      DLBCL (median (range) 5.7% (2.5-13.5)) and FL (median (range) 5.3% (2.3-11.9))
      with a clonal rearrangement. CONCLUSIONS: Use of BIOMED-2 primers has
      significantly reduced the false negative rate associated with GC/PGCL when
      compared with consensus primers, and the inclusion of DJH rearrangements
      represents a potential complementary target for clonality assessment, as SHM is
      thought not to occur in these types of rearrangements.

PMID- 16816170
TI  - Endobronchial ultrasound-guided fine-needle aspiration and liquid-based thin
      layer cytology.
AB  - BACKGROUND: Optimal management of patients with lung cancer requires accurate
      cell typing of tumours and staging at the time of diagnosis. Endobronchial
      ultrasound-guided lymph node aspiration as a method of diagnosing and staging
      lung cancer is a relatively new technique. AIM: To report the use of liquid-based
      thin-layer cytology for the processing and reporting of these specimens. METHODS:
      The specimens obtained from 80 patients were processed using the ThinPrep system,
      with the remainder of the samples being processed as a cell block. RESULTS: 40 of
      the 81 procedures yielded malignant cells (30 non-small cell carcinoma, 8 small
      cell carcinoma and 2 combined small-cell carcinoma/non-small-cell carcinoma). The
      cell blocks were found to contain sufficient material to allow the
      immunohistochemical characterisation of tumour cells with a range of antibodies.
      CONCLUSION: The use of liquid-based-thin-layer cytological techniques provides
      high-quality specimens for diagnostic purposes. When used in conjunction with
      cell blocks, sufficient material may be obtained to allow immunohistochemical
      studies to confirm the tumour cell type. Given the current move towards
      centralisation of pathology services, this approach gives the pathologist high
      quality specimens without the need for direct onsite support at the time of the
      procedure.

PMID- 16816171
TI  - Microvascular proliferation in congenital vascular malformations of skin and soft
      tissue.
AB  - BACKGROUND: Congenital vascular malformations (VMs) are mass-forming lesions that
      usually progress slowly, but may become symptomatic because of episodes of sudden
      growth and pain, particularly those with a substantial component of arteriovenous
      shunting. AIM: To systematically investigate the features of microvascular
      proliferation in a large series of surgically treated VMs. METHODS: 107 resection
      specimens of clinically and histologically well-documented VMs were screened for
      the presence and extent of microvascular proliferation, based on morphological
      parameters, microvessel density (MVD), mast cell density (MCD) and proliferative
      activity (Ki-67 labelling index) of endothelial cells (ECs) and vascular smooth
      muscle cells (VSMCs). The extent of microvascular proliferation was correlated
      with the histological type of VM and clinical characteristics of patients.
      RESULTS: Microvascular proliferation was observed in 32 (30%) of all VMs, of
      which 30 cases seemed to be arteriovenous malformations. MVD in areas of
      microvascular proliferation was 282 (186)/mm(2) vs 13 (9)/mm(2) in areas with
      mature vessels. Both ECs and VSMCs in these areas showed high Ki-67 labelling
      indexes (mean (SD) 15 (18) and 17 (24)/mm(2), respectively). In all lesions, a
      positive correlation was found between MCD and MVD. Age, sex and location of VM
      had no predictive value for the occurrence of microvascular proliferation.
      However, if present, the involved tissue areas were larger and the proliferative
      activity of EC was higher in male patients than in female patients. CONCLUSIONS:
      Recognition of microvascular proliferation as a not uncommon feature, congenital
      arteriovenous malformations provide new insight into the growth behaviour and
      vascular composition of these lesions.

PMID- 16816172
TI  - Diagnosis of fusariosis in urine cytology.
AB  - Fusarium is a filamentous fungus widely distributed in plants and in the soil.
      Most species are more common at tropical and subtropical areas. Besides being a
      common contaminant and a well-known plant pathogen, Fusarium sp may cause various
      infections in humans. However, it has not yet been reported as being the pathogen
      of urinary tract infection. A 67-year-old woman had extracorporeal shock wave
      lithotripsy and percutaneous nephrolithotomy for renal stones 7 and 6 years ago,
      respectively. She had had fever, chillness, urinary urgency and frequency for 6
      days. Routine testing of urine showed numerous leucocytes. She was admitted under
      the impression of urinary tract infection. On admission, many spindle-shaped
      structures were found in the urine smears. This shows that Fusarium was
      identified. Fusarium may be the pathogen of the urinary tract infection,
      particularly when urolithiasis is present.

PMID- 16816173
TI  - The Brucella abortus cyclic beta-1,2-glucan virulence factor is substituted with
      O-ester-linked succinyl residues.
AB  - Brucella periplasmic cyclic beta-1,2-glucan plays an important role during
      bacterium-host interaction. Nuclear magnetic resonance spectrometry analysis,
      thin-layer chromatography, and DEAE-Sephadex chromatography were used to
      characterize Brucella abortus cyclic glucan. In the present study, we report that
      a fraction of B. abortus cyclic beta-1,2-glucan is substituted with succinyl
      residues, which confer anionic character on the cyclic beta-1,2-glucan. The
      oligosaccharide backbone is substituted at C-6 positions with an average of two
      succinyl residues per glucan molecule. This O-ester-linked succinyl residue is
      the only substituent of Brucella cyclic glucan. A B. abortus open reading frame
      (BAB1_1718) homologous to Rhodobacter sphaeroides glucan succinyltransferase
      (OpgC) was identified as the gene encoding the enzyme responsible for cyclic
      glucan modification. This gene was named cgm for cyclic glucan modifier and is
      highly conserved in Brucella melitensis and Brucella suis. Nucleotide sequencing
      revealed that B. abortus cgm consists of a 1,182-bp open reading frame coding for
      a predicted membrane protein of 393 amino acid residues (42.7 kDa) 39% identical
      to Rhodobacter sphaeroides succinyltransferase. cgm null mutants in B. abortus
      strains 2308 and S19 produced neutral glucans without succinyl residues,
      confirming the identity of this protein as the cyclic-glucan succinyltransferase
      enzyme. In this study, we demonstrate that succinyl substituents of cyclic beta
      1,2-glucan of B. abortus are necessary for hypo-osmotic adaptation. On the other
      hand, intracellular multiplication and mouse spleen colonization are not affected
      in cgm mutants, indicating that cyclic-beta-1,2-glucan succinylation is not
      required for virulence and suggesting that no low-osmotic stress conditions must
      be overcome during infection.

PMID- 16816174
TI  - DevA, a GntR-like transcriptional regulator required for development in
      Streptomyces coelicolor.
AB  - The gram-positive filamentous bacterium Streptomyces coelicolor has a complex
      developmental cycle with three distinct phases: growth of the substrate mycelium,
      development of reproductive structures called aerial hyphae, and differentiation
      of these aerial filaments into long chains of exospores. During a transposon
      mutagenesis screen, we identified a novel gene (devA) required for proper
      development. The devA mutant produced only rare aerial hyphae, and those that
      were produced developed aberrant spore chains that were much shorter than wild
      type chains and had misplaced septa. devA encodes a member of the GntR
      superfamily, a class of transcriptional regulators that typically respond to
      metabolite effector molecules. devA forms an operon with the downstream gene
      devB, which encodes a putative hydrolase that is also required for aerial
      mycelium formation on R5 medium. S1 nuclease protection analysis showed that
      transcription from the single devA promoter was temporally associated with
      vegetative growth, and enhanced green fluorescent protein transcriptional fusions
      showed that transcription was spatially confined to the substrate hyphae in the
      wild type. In contrast, devAB transcript levels were dramatically upregulated in
      a devA mutant and the devA promoter was also active in aerial hyphae and spores
      in this background, suggesting that DevA might negatively regulate its own
      production. This suggestion was confirmed by gel mobility shift assays that
      showed that DevA binds its own promoter region in vitro.

PMID- 16816175
TI  - Genetic evidence for the requirement of RecA loading activity in SOS induction
      after UV irradiation in Escherichia coli.
AB  - The SOS response in Escherichia coli results in the coordinately induced
      expression of more than 40 genes which occurs when cells are treated with DNA
      damaging agents. This response is dependent on RecA (coprotease), LexA
      (repressor), and the presence of single-stranded DNA (ssDNA). A prerequisite for
      SOS induction is the formation of a RecA-ssDNA filament. Depending on the DNA
      substrate, the RecA-ssDNA filament is produced by either RecBCD, RecFOR, or a
      hybrid recombination mechanism with specific enzyme activities, including
      helicase, exonuclease, and RecA loading. In this study we examined the role of
      RecA loading activity in SOS induction after UV irradiation. We performed a
      genetic analysis of SOS induction in strains with a mutation which eliminates
      RecA loading activity in the RecBCD enzyme (recB1080 allele). We found that RecA
      loading activity is essential for SOS induction. In the recB1080 mutant RecQ
      helicase is not important, whereas RecJ nuclease slightly decreases SOS induction
      after UV irradiation. In addition, we found that the recB1080 mutant exhibited
      constitutive expression of the SOS regulon. Surprisingly, this constitutive SOS
      expression was dependent on the RecJ protein but not on RecFOR, implying that
      there is a different mechanism of RecA loading for constitutive SOS expression.

PMID- 16816176
TI  - The SloR/Dlg metalloregulator modulates Streptococcus mutans virulence gene
      expression.
AB  - Metal ion availability in the human oral cavity plays a putative role in
      Streptococcus mutans virulence gene expression and in appropriate formation of
      the plaque biofilm. In this report, we present evidence that supports such a role
      for the DtxR-like SloR metalloregulator (called Dlg in our previous publications)
      in this oral pathogen. Specifically, the results of gel mobility shift assays
      revealed the sloABC, sloR, comDE, ropA, sod, and spaP promoters as targets of
      SloR binding. We confirmed differential expression of these genes in a GMS584
      SloR-deficient mutant versus the UA159 wild-type progenitor by real-time
      semiquantitative reverse transcriptase PCR experiments. The results of additional
      expression studies support a role for SloR in S. mutans control of
      glucosyltransferases, glucan binding proteins, and genes relevant to antibiotic
      resistance. Phenotypic analysis of GMS584 revealed that it forms aberrant
      biofilms on an abiotic surface, is compromised for genetic competence, and
      demonstrates heightened incorporation of iron and manganese as well as resistance
      to oxidative stress compared to the wild type. Taken together, these findings
      support a role for SloR in S. mutans adherence, biofilm formation, genetic
      competence, metal ion homeostasis, oxidative stress tolerance, and antibiotic
      gene regulation, all of which contribute to S. mutans-induced disease.

PMID- 16816177
TI  - Biochemical and molecular characterization of a Na+-translocating F1Fo-ATPase
      from the thermoalkaliphilic bacterium Clostridium paradoxum.
AB  - Clostridium paradoxum is an anaerobic thermoalkaliphilic bacterium that grows
      rapidly at pH 9.8 and 56 degrees C. Under these conditions, growth is sensitive
      to the F-type ATP synthase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD),
      suggesting an important role for this enzyme in the physiology of C. paradoxum.
      The ATP synthase was characterized at the biochemical and molecular levels. The
      purified enzyme (30-fold purification) displayed the typical subunit pattern for
      an F1Fo-ATP synthase but also included the presence of a stable oligomeric c-ring
      that could be dissociated by trichloroacetic acid treatment into its monomeric c
      subunits. The purified ATPase was stimulated by sodium ions, and sodium provided
      protection against inhibition by DCCD that was pH dependent. ATP synthesis in
      inverted membrane vesicles was driven by an artificially imposed chemical
      gradient of sodium ions in the presence of a transmembrane electrical potential
      that was sensitive to monensin. Cloning and sequencing of the atp operon revealed
      the presence of a sodium-binding motif in the membrane-bound c subunit (viz.,
      Q28, E61, and S62). On the basis of these properties, the F1Fo-ATP synthase of C.
      paradoxum is a sodium-translocating ATPase that is used to generate an
      electrochemical gradient of + that could be used to drive other membrane-bound
      bioenergetic processes (e.g., solute transport or flagellar rotation). In support
      of this proposal are the low rates of ATP synthesis catalyzed by the enzyme and
      the lack of the C-terminal region of the epsilon subunit that has been shown to
      be essential for coupled ATP synthesis.

PMID- 16816178
TI  - Autoregulation of the MisR/MisS two-component signal transduction system in
      Neisseria meningitidis.
AB  - Two-component regulatory systems are involved in processes important for
      bacterial pathogenesis. The proposed misR/misS (or phoP/phoQ) system is one of
      four two-component systems of the obligate human pathogen Neisseria meningitidis.
      Inactivation of this system results in loss of phosphorylation of the
      lipooligosaccharide inner core and causes attenuation in a mouse model of
      meningococcal infection. MisR and the cytoplasmic domain of MisS were purified as
      His6 and maltose binding protein fusion proteins, respectively. The MisS fusion
      was shown to be autophosphorylated in the presence of ATP, and the phosphoryl
      group was subsequently transferred to MisR. The phosphotransfer reaction was
      halted with a MisR/D52A mutation, while a MisS/H246A mutation prevented
      autophosphorylation. Specific interaction of phosphorylated MisR (MisR
      approximately P) and MisR with the misR promoter was demonstrated by gel mobility
      shift assays, where MisR approximately P exhibited higher affinity than did the
      nonphosphorylated protein. The transcriptional start site of the misRS operon was
      mapped, and DNase I protection assays revealed that MisR interacted with a 15-bp
      region upstream of the transcriptional start site that shared no similarity to
      binding motifs of other two-component systems. Transcriptional reporter studies
      suggested that MisR phosphorylation is critical for the autoinduction of the
      misRS operon. Limited Mg2+ concentration failed to induce expression of the misRS
      operon, which is the only operon now proven to be under the direct control of the
      MisRS two-component system. Thus, these results indicate that the meningococcal
      MisRS system constitutes a functional signal transduction circuit and that both
      components are critical in the autoregulation of their expression.

PMID- 16816179
TI  - Mutations of the membrane-bound disulfide reductase DsbD that block electron
      transfer steps from cytoplasm to periplasm in Escherichia coli.
AB  - The cytoplasmic membrane protein DsbD keeps the periplasmic disulfide isomerase
      DsbC reduced, using the cytoplasmic reducing power of thioredoxin. DsbD contains
      three domains, each containing two reactive cysteines. One membrane-embedded
      domain, DsbDbeta, transfers electrons from thioredoxin to the carboxy-terminal
      thioredoxin-like periplasmic domain DsbDgamma. To evaluate the role of conserved
      amino acid residues in DsbDbeta in the electron transfer process, we substituted
      alanines for each of 19 conserved amino acid residues and assessed the in vivo
      redox states of DsbC and DsbD. The mutant DsbDs of 11 mutants which caused
      defects in DsbC reduction showed relatively oxidized redox states. To analyze the
      redox state of each DsbD domain, we constructed a thrombin-cleavable DsbD
      (DsbDTH) from which we could generate all three domains as separate polypeptide
      chains by thrombin treatment in vitro. We divided the mutants with strong defects
      into two classes. The first mutant class consists of mutant DsbDbeta proteins
      that cannot receive electrons from cytoplasmic thioredoxin, resulting in a DsbD
      that has all six of its cysteines disulfide bonded. The second mutant class
      represents proteins in which the transfer of electrons from DsbDbeta to DsbDgamma
      appears to be blocked. This class includes the mutant with the most clear-cut
      defect, P284A. We relate the properties of the mutants to the positions of the
      amino acids in the structure of DsbD and discuss mechanisms that would interfere
      with the electron transfer process.

PMID- 16816180
TI  - Limited role for the DsrA and RprA regulatory RNAs in rpoS regulation in
      Salmonella enterica.
AB  - RpoS, the sigma factor of enteric bacteria that responds to stress and stationary
      phase, is subject to complex regulation acting at multiple levels, including
      transcription, translation, and proteolysis. Increased translation of rpoS mRNA
      during growth at low temperature, after osmotic challenge, or with a
      constitutively activated Rcs phosphorelay depends on two trans-acting small
      regulatory RNAs (sRNAs) in Escherichia coli. The DsrA and RprA sRNAs are both
      highly conserved in Salmonella enterica, as is their target, an inhibitory
      antisense element within the rpoS untranslated leader. Analysis of dsrA and rprA
      deletion mutants indicates that while the increased translation of RpoS in
      response to osmotic challenge is conserved in S. enterica, dependence on these
      two sRNA regulators is much reduced. Furthermore, low-temperature growth or
      constitutive RcsC activation had only modest effects on RpoS expression, and
      these increases were, respectively, independent of dsrA or rprA function. This
      lack of conservation of sRNA function suggests surprising flexibility in RpoS
      regulation.

PMID- 16816181
TI  - Molecular characterization of Pantoea stewartii subsp. stewartii HrpY, a
      conserved response regulator of the Hrp type III secretion system, and its
      interaction with the hrpS promoter.
AB  - Pantoea stewartii subsp. stewartii is a bacterial pathogen of corn. Its
      pathogenicity depends on the translocation of effector proteins into host cells
      by the Hrp type III secretion system. We previously showed by genetic analysis
      that the HrpX sensor kinase and the HrpY response regulator are at the head of a
      complex cascade of regulators controlling hrp/hrc secretion and wts effector
      genes. This cascade also includes the HrpS response regulator and the HrpL
      alternative sigma factor. These regulators are shared among many important plant
      pathogens in the genera Pantoea, Erwinia, and Pseudomonas. In this study, we
      dissect the regulatory elements in the hrpS promoter region, using genetic and
      biochemical approaches, and show how it integrates various environmental signals,
      only some of which are dependent on phosphorylation of HrpY. Primer extension
      located the transcriptional start site of hrpS at a sigma70 promoter 601 bp
      upstream of the open reading frame. Electrophoretic mobility shift assays and
      DNase I footprinting analysis demonstrated that HrpY binds to conserved
      regulatory elements immediately adjacent to this promoter, and its binding
      affinity was increased by phosphorylation at D57. A consensus sequence for the
      two direct repeats bound by HrpY is proposed. Deletion analysis of the promoter
      region revealed that both the HrpY binding site and additional sequences farther
      upstream, including a putative integration host factor binding site, are required
      for hrpS expression. This finding suggests that other unknown regulatory proteins
      may act cooperatively with HrpY.

PMID- 16816182
TI  - H-NS represses inv transcription in Yersinia enterocolitica through competition
      with RovA and interaction with YmoA.
AB  - Yersinia enterocolitica is able to efficiently invade Peyer's patches with the
      aid of invasin, an outer member protein involved in the attachment and invasion
      of M cells. Invasin is encoded by inv, which is positively regulated by RovA in
      both Y. enterocolitica and Yersinia pseudotuberculosis while negatively regulated
      by YmoA in Y. enterocolitica and H-NS in Y. pseudotuberculosis. In this study we
      present data indicating H-NS and RovA bind directly and specifically to the inv
      promoter of Y. enterocolitica. We also show that RovA and H-NS from Y.
      enterocolitica bind to a similar region of the inv promoter and suggest they
      compete for binding sites. This is similar to recently published data from Y.
      pseudotuberculosis, revealing a potentially conserved mechanism of inv regulation
      between Y. enterocolitica and Y. pseudotuberculosis. Furthermore, we present data
      suggesting H-NS and YmoA form a repression complex on the inv promoter, with H-NS
      providing the binding specificity and YmoA interacting with H-NS to form a
      repression complex. We also demonstrate that deletion of the predicted H-NS
      binding region relieves the requirement for RovA-dependent transcription of the
      inv promoter, consistent with RovA acting as a derepressor of H-NS-mediated
      repression. Levels of H-NS and YmoA are similar between 26 degrees C and 37
      degrees C, suggesting that the H-NS/YmoA repression complex is present at both
      temperatures, while the levels of rovA transcript are low at 37 degrees C and
      high at 26 degrees C, leading to expression of inv at 26 degrees C. Expression of
      RovA at 37 degrees C results in transcription of inv and production of invasin.
      Data presented here support a model of inv regulation where the level of RovA
      within the cell governs inv expression. As RovA levels increase, RovA can
      successfully compete for binding to the inv promoter with the H-NS/YmoA complex,
      resulting in derepression of inv transcription.

PMID- 16816183
TI  - Occurrence of two 5-aminolevulinate biosynthetic pathways in Streptomyces nodosus
      subsp. asukaensis is linked with the production of asukamycin.
AB  - We report the results of cloning genes for two key biosynthetic enzymes of
      different 5-aminolevulinic acid (ALA) biosynthetic routes from Streptomyces. The
      genes encode the glutamyl-tRNAGlu reductase (GluTR) of the C5 pathway and the ALA
      synthase (ALAS) of the Shemin pathway. While Streptomyces coelicolor A3(2)
      synthesizes ALA via the C5 route, both pathways are operational in Streptomyces
      nodosus subsp. asukaensis, a producer of asukamycin. In this strain, the C5 route
      produces ALA for tetrapyrrole biosynthesis; the ALA formed by the Shemin pathway
      serves as a precursor of the 2-amino-3-hydroxycyclopent-2-enone moiety (C5N
      unit), an antibiotic component. The growth of S. nodosus and S. coelicolor
      strains deficient in the GluTR genes (gtr) is strictly dependent on ALA or heme
      supplementation, whereas the defect in the ALAS-encoding gene (hemA-asuA)
      abolishes the asukamycin production in S. nodosus. The recombinant hemA-asuA gene
      was expressed in Escherichia coli and in Streptomyces, and the encoded enzyme
      activity was demonstrated both in vivo and in vitro. The hemA-asuA gene is
      situated within a putative cluster of asukamycin biosynthetic genes. This is the
      first report about the cloning of genes for two different ALA biosynthetic routes
      from a single bacterium.

PMID- 16816184
TI  - Interplay of the Wzx translocase and the corresponding polymerase and chain
      length regulator proteins in the translocation and periplasmic assembly of
      lipopolysaccharide o antigen.
AB  - Genetic evidence suggests that a family of bacterial and eukaryotic integral
      membrane proteins (referred to as Wzx and Rft1, respectively) mediates the
      transbilayer movement of isoprenoid lipid-linked glycans. Recent work in our
      laboratory has shown that Wzx proteins involved in O-antigen lipopolysaccharide
      (LPS) assembly have relaxed specificity for the carbohydrate structure of the O
      antigen subunit. Furthermore, the proximal sugar bound to the isoprenoid lipid
      carrier, undecaprenyl-phosphate (Und-P), is the minimal structure required for
      translocation. In Escherichia coli K-12, N-acetylglucosamine (GlcNAc) is the
      proximal sugar of the O16 and enterobacterial common antigen (ECA) subunits. Both
      O16 and ECA systems have their respective translocases, WzxO16 and WzxE, and also
      corresponding polymerases (WzyO16 and WzyE) and O-antigen chain-length regulators
      (WzzO16 and WzzE), respectively. In this study, we show that the E. coli wzxE
      gene can fully complement a wzxO16 translocase deletion mutant only if the
      majority of the ECA gene cluster is deleted. In addition, we demonstrate that
      introduction of plasmids expressing either the WzyE polymerase or the WzzE chain
      length regulator proteins drastically reduces the O16 LPS-complementing activity
      of WzxE. We also show that this property is not unique to WzxE, since WzxO16 and
      WzxO7 can cross-complement translocase defects in the O16 and O7 antigen clusters
      only in the absence of their corresponding Wzz and Wzy proteins. These genetic
      data are consistent with the notion that the translocation of O-antigen and ECA
      subunits across the plasma membrane and the subsequent assembly of periplasmic O
      antigen and ECA Und-PP-linked polymers depend on interactions among Wzx, Wzz, and
      Wzy, which presumably form a multiprotein complex.

PMID- 16816185
TI  - GlpD and PlsB participate in persister cell formation in Escherichia coli.
AB  - Bacterial populations produce dormant persister cells that are resistant to
      killing by all antibiotics currently in use, a phenomenon known as multidrug
      tolerance (MDT). Persisters are phenotypic variants of the wild type and are
      largely responsible for MDT of biofilms and stationary populations. We recently
      showed that a hipBA toxin/antitoxin locus is part of the MDT mechanism in
      Escherichia coli. In an effort to find additional MDT genes, an E. coli
      expression library was selected for increased survival to ampicillin. A clone
      with increased persister production was isolated and was found to overexpress the
      gene for the conserved aerobic sn-glycerol-3-phosphate dehydrogenase GlpD. The
      GlpD overexpression strain showed increased tolerance to ampicillin and
      ofloxacin, while a strain with glpD deleted had a decreased level of persisters
      in the stationary state. This suggests that GlpD is a component of the MDT
      mechanism. Further genetic studies of mutants affected in pathways involved in sn
      glycerol-3-phosphate metabolism have led to the identification of two additional
      multidrug tolerance loci, glpABC, the anaerobic sn-glycerol-3-phosphate
      dehydrogenase, and plsB, an sn-glycerol-3-phosphate acyltransferase.

PMID- 16816186
TI  - RNase E maintenance of proper FtsZ/FtsA ratio required for nonfilamentous growth
      of Escherichia coli cells but not for colony-forming ability.
AB  - Inactivation or deletion of the RNase E-encoding rne gene of Escherichia coli
      results in the growth of bacterial cells as filamentous chains in liquid culture
      (K. Goldblum and D. Apirion, J. Bacteriol. 146:128-132, 1981) and the loss of
      colony-forming ability (CFA) on solid media. RNase E dysfunction is also
      associated with abnormal processing of ftsQAZ transcripts (K. Cam, G. Rome, H. M.
      Krisch, and J.-P. Bouche, Nucleic Acids Res. 24:3065-3070, 1996), which encode
      proteins having a central role in septum formation during cell division. We show
      here that RNase E regulates the relative abundances of FtsZ and FtsA proteins and
      that RNase E depletion results in decreased FtsZ, increased FtsA, and
      consequently an altered FtsZ/FtsA ratio. However, while restoration of the level
      of FtsZ to normal in rne null mutant bacteria reverses the filamentation
      phenotype, it does not restore CFA. Conversely, overexpression of a related
      RNase, RNase G, in rne-deleted bacteria restores CFA, as previously reported,
      without affecting FtsZ abundance. Our results demonstrate that RNase E activity
      is required to maintain a proper cellular ratio of the FtsZ and FtsA proteins in
      E. coli but that FtsZ deficiency does not account for the nonviability of cells
      lacking RNase E.

PMID- 16816187
TI  - Regulation of LiaRS-dependent gene expression in bacillus subtilis:
      identification of inhibitor proteins, regulator binding sites, and target genes
      of a conserved cell envelope stress-sensing two-component system.
AB  - The regulatory network of the cell envelope stress response in Bacillus subtilis
      involves both extracytoplasmic function sigma-factors and two-component signal
      transducing systems. One such system, LiaRS, responds to cell wall antibiotics
      that interfere with the undecaprenol cycle and to perturbation of the cytoplasmic
      membrane. It is encoded by the last two genes of the liaIHGFSR locus. Here, we
      analyzed the expression of two LiaR-dependent operons, liaIHGFSR and yhcYZ-yhdA,
      and characterized a palindromic sequence required for LiaR-dependent activation.
      Since induction of the strong liaI promoter leads to both liaIH and liaIHGFRS
      transcripts, LiaR is positively autoregulated. Systematic deletion analysis of
      the liaI operon revealed that LiaF is a potent negative regulator of LiaR
      dependent gene expression: a nonpolar liaF deletion led to constitutive
      activation of both characterized LiaR-dependent promoters. The liaF gene is
      conserved in both sequence and genomic context in the Firmicutes group of gram
      positive bacteria, located directly upstream of liaSR orthologs. LiaH, a homolog
      of Escherichia coli phage shock protein A, also plays a more subtle role in
      negatively modulating the bacitracin-inducible expression from LiaR-dependent
      promoters. Our results support a model in which the LiaFRS module integrates both
      positive and negative feedback loops to transduce cell envelope stress signals.

PMID- 16816188
TI  - Regulation of the Myxococcus xanthus C-signal-dependent Omega4400 promoter by the
      essential developmental protein FruA.
AB  - The bacterium Myxococcus xanthus employs extracellular signals to coordinate
      aggregation and sporulation during multicellular development. Extracellular,
      contact-dependent signaling that involves the CsgA protein (called C-signaling)
      activates FruA, a putative response regulator that governs a branched signaling
      pathway inside cells. One branch regulates cell movement, leading to aggregation.
      The other branch regulates gene expression, leading to sporulation. C-signaling
      is required for full expression of most genes induced after 6 h into development,
      including the gene identified by Tn5 lac insertion Omega4400. To determine if
      FruA is a direct regulator of Omega4400 transcription, a combination of in vivo
      and in vitro experiments was performed. Omega4400 expression was abolished in a
      fruA mutant. The DNA-binding domain of FruA bound specifically to DNA upstream of
      the promoter -35 region in vitro. Mutations between bp -86 and -77 greatly
      reduced binding. One of these mutations had been shown previously to reduce
      Omega4400 expression in vivo and make it independent of C-signaling. For the
      first time, chromatin immunoprecipitation (ChIP) experiments were performed on M.
      xanthus. The ChIP experiments demonstrated that FruA is associated with the
      Omega4400 promoter region late in development, even in the absence of C
      signaling. Based on these results, we propose that FruA directly activates
      Omega4400 transcription to a moderate level prior to C-signaling and, in response
      to C-signaling, binds near bp -80 and activates transcription to a higher level.
      Also, the highly localized effects of mutations between bp -86 and -77 on DNA
      binding in vitro, together with recently published footprints, allow us to
      predict a consensus binding site of GTCG/CGA/G for the FruA DNA-binding domain.

PMID- 16816189
TI  - An unstable competence-induced protein, CoiA, promotes processing of donor DNA
      after uptake during genetic transformation in Streptococcus pneumoniae.
AB  - Natural genetic transformation in Streptococcus pneumoniae entails
      transcriptional activation of at least two sets of genes. One set of genes,
      activated by the competence-specific response regulator ComE, is involved in
      initiating competence, whereas a second set is activated by the competence
      specific alternative sigma factor ComX and functions in DNA uptake and
      recombination. Here we report an initial characterization of CoiA, a ComX
      dependent gene product that is induced during competence and is required for
      transformation. CoiA is widely conserved among gram-positive bacteria, and in
      streptococci, the entire coiA locus composed of four genes is conserved. By use
      of immunoblot assay, we show that, similar to its message, CoiA protein is
      transient, appearing at 10 min and largely disappearing by 30 min post-competence
      induction. Using complementation analysis, we establish that coiA is the only
      gene of this induced locus needed for transformability. We find no indication of
      CoiA having a role in regulating competence. Finally, using 32P- and 3H-labeled
      donor DNA, we demonstrate that a coiA mutant can internalize normal amounts of
      donor DNA compared to the wild-type strain but is unable to process it into
      viable transformants, suggesting a role for CoiA after DNA uptake, either in DNA
      processing or recombination.

PMID- 16816190
TI  - RecA and RadA proteins of Brucella abortus do not perform overlapping protective
      DNA repair functions following oxidative burst.
AB  - Very little is known about the role of DNA repair networks in Brucella abortus
      and its role in pathogenesis. We investigated the roles of RecA protein, DNA
      repair, and SOS regulation in B. abortus. While recA mutants in most bacterial
      species are hypersensitive to UV damage, surprisingly a B. abortus recA null
      mutant conferred only modest sensitivity. We considered the presence of a second
      RecA protein to account for this modest UV sensitivity. Analyses of the Brucella
      spp. genomes and our molecular studies documented the presence of only one recA
      gene, suggesting a RecA-independent repair process. Searches of the available
      Brucella genomes revealed some homology between RecA and RadA, a protein
      implicated in E. coli DNA repair. We considered the possibility that B. abortus
      RadA might be compensating for the loss of RecA by promoting similar repair
      activities. We present functional analyses that demonstrated that B. abortus RadA
      complements a radA defect in E. coli but could not act in place of the B. abortus
      RecA. We show that RecA but not RadA was required for survival in macrophages. We
      also discovered that recA was expressed at high constitutive levels, due to
      constitutive LexA cleavage by RecA, with little induction following DNA damage.
      Higher basal levels of RecA and its SOS-regulated gene products might protect
      against DNA damage experienced following the oxidative burst within macrophages.

PMID- 16816191
TI  - sigma28-dependent transcription in Salmonella enterica is independent of
      flagellar shearing.
AB  - The FlgM anti-sigma28 factor is secreted in response to flagellar hook-basal body
      completion to allow sigma28-dependent transcription of genes needed late in
      flagellar assembly, such as the flagellin structural gene, fliC. A long-standing
      hypothesis was that one role of FlgM secretion was to allow rapid expression of
      flagellin in response to shearing. We tested this hypothesis by following FlgM
      secretion and fliC transcription in response to flagellar shearing. Experiments
      showed that the level of FlgM inside the cell was unchanged after shearing
      whereas the extracellular FlgM levels increased in the growth medium as time
      passed. Identical results were obtained with cells that were not exposed to shear
      forces: internal FlgM levels remained constant while external FlgM levels rose
      with time at rates similar to those for the sheared culture. Consistent with this
      find, FlgM/sigma28-dependent class 3 gene expression was unaffected by flagellar
      shearing but was affected by the growth phase of the cell. Regardless of exposure
      to shear forces, flagellar class 3 transcription rose sharply and then declined.
      These results demonstrate that flagellar regrowth following shearing is
      independent of FlgM secretion.

PMID- 16816192
TI  - Constitutive activation of two-component response regulators: characterization of
      VirG activation in Agrobacterium tumefaciens.
AB  - Response regulators are the ultimate modulators in two-component signal
      transduction pathways. The N-terminal receiver domains generally accept
      phosphates from cognate histidine kinases to control output. VirG for example,
      the response regulator of the VirA/VirG two-component system in Agrobacterium
      tumefaciens, mediates the expression of virulence genes in response to plant host
      signals. Response regulators have a highly conserved structure and share a
      similar conformational activation upon phosphorylation, yet the sequence and
      structural features that determine or perturb the cooperative activation events
      are ill defined. Here we use VirG and the unique features of the Agrobacterium
      system to extend our understanding of the response regulator activation. Two
      previously isolated constitutive VirG mutants, VirGN54D and VirGI77V/D52E,
      provide the foundation for our studies. In vivo phosphorylation patterns
      establish that VirGN54D is able to accumulate phosphates from small-molecule
      phosphate donors, such as acetyl phosphate, while the VirGI77V/D52E allele
      carries conformational changes mimicking the active conformation. Further
      structural alterations on these two alleles begin to reveal the changes necessary
      for response regulator activation.

PMID- 16816193
TI  - GlcNAc-6P levels modulate the expression of Curli fibers by Escherichia coli.
AB  - Curli are extracellular surface fibers that are produced by many members of the
      Enterobacteriaceae and contribute to biofilm formation. The environmental cues
      that promote biofilm formation are poorly understood. We found that deletion of
      the N-acetylglucosamine-6-phosphate (GlcNAc-6P) deacetylase gene, nagA, resulted
      in decreased transcription from the curli-specific promoters csgBA and csgDEFG
      and a corresponding decrease in curli production in Escherichia coli. nagA is in
      an operon that contains nagB, nagC, nagD, and nagE, whose products are required
      for utilization of GlcNAc as a carbon source. NagC is a repressor of the nagBACD
      and nagE genes in the absence of intracellular GlcNAc-6P. We found that nagC
      mutants were also defective in curli production. Growth of a wild-type strain on
      media containing additional GlcNAc reduced curli gene transcription to a level
      similar to the level observed when nagA was deleted. The defect in curli
      production in nagA or nagC mutants was alleviated by deletion of the GlcNAc
      transporter gene, nagE. Curli-producing DeltanagA suppressor mutants whose cells
      were unable to take up GlcNAc were isolated. These results suggest that elevated
      levels of intracellular GlcNAc-6P signal cells to down-regulate curli gene
      expression.

PMID- 16816194
TI  - CYP153A6, a soluble P450 oxygenase catalyzing terminal-alkane hydroxylation.
AB  - The first and key step in alkane metabolism is the terminal hydroxylation of
      alkanes to 1-alkanols, a reaction catalyzed by a family of integral-membrane
      diiron enzymes related to Pseudomonas putida GPo1 AlkB, by a diverse group of
      methane, propane, and butane monooxygenases and by some membrane-bound cytochrome
      P450s. Recently, a family of cytoplasmic P450 enzymes was identified in
      prokaryotes that allow their host to grow on aliphatic alkanes. One member of
      this family, CYP153A6 from Mycobacterium sp. HXN-1500, hydroxylates medium-chain
      length alkanes (C6 to C11) to 1-alkanols with a maximal turnover number of 70
      min(-1) and has a regiospecificity of > or =95% for the terminal carbon atom
      position. Spectroscopic binding studies showed that C6-to-C11 aliphatic alkanes
      bind in the active site with Kd values varying from approximately 20 nM to 3.7
      microM. Longer alkanes bind more strongly than shorter alkanes, while the
      introduction of sterically hindering groups reduces the affinity. This suggests
      that the substrate-binding pocket is shaped such that linear alkanes are
      preferred. Electron paramagnetic resonance spectroscopy in the presence of the
      substrate showed the formation of an enzyme-substrate complex, which confirmed
      the binding of substrates observed in optical titrations. To rationalize the
      experimental observations on a molecular scale, homology modeling of CYP153A6 and
      docking of substrates were used to provide the first insight into structural
      features required for terminal alkane hydroxylation.

PMID- 16816195
TI  - Global transcriptome analysis of Tropheryma whipplei in response to temperature
      stresses.
AB  - Tropheryma whipplei, the agent responsible for Whipple disease, is a poorly known
      pathogen suspected to have an environmental origin. The availability of the
      sequence of the 0.92-Mb genome of this organism made a global gene expression
      analysis in response to thermal stresses feasible, which resulted in unique
      transcription profiles. A few genes were differentially transcribed after 15 min
      of exposure at 43 degrees C. The effects observed included up-regulation of the
      dnaK regulon, which is composed of six genes and is likely to be under control of
      two HspR-associated inverted repeats (HAIR motifs) found in the 5' region.
      Putative virulence factors, like the RibC and IspDF proteins, were also
      overexpressed. While it was not affected much by heat shock, the T. whipplei
      transcriptome was strongly modified following cold shock at 4 degrees C. For the
      149 genes that were differentially transcribed, eight regulons were identified,
      and one of them was composed of five genes exhibiting similarity with genes
      encoding ABC transporters. Up-regulation of these genes suggested that there was
      an increase in nutrient uptake when the bacterium was exposed to cold stress. As
      observed for other bacterial species, the major classes of differentially
      transcribed genes encode membrane proteins and enzymes involved in fatty acid
      biosynthesis, indicating that membrane modifications are critical. Paradoxically,
      the heat shock proteins GroEL2 and ClpP1 were up-regulated. Altogether, the data
      show that despite the lack of classical regulation pathways, T. whipplei exhibits
      an adaptive response to thermal stresses which is consistent with its specific
      environmental origin and could allow survival under cold conditions.

PMID- 16816197
TI  - Phylogenomic and biochemical characterization of three Legionella pneumophila
      polypeptide deformylases.
AB  - Legionella pneumophila is a gram-negative facultative intracellular human
      pathogen that can cause fatal Legionnaires' disease. Polypeptide deformylase
      (PDF) is a novel broad-spectrum antibacterial target, and reports of inhibitors
      of PDF with potent activities against L. pneumophila have been published
      previously. Here, we report the identification of not one but three putative pdf
      genes, pdfA, pdfB, and pdfC, in the complete genome sequences of three strains of
      L. pneumophila. Phylogenetic analysis showed that L. pneumophila PdfA is most
      closely related to the commonly known gamma-proteobacterial PDFs encoded by the
      gene def. PdfB and PdfC are more divergent and do not cluster with any specific
      bacterial or eukaryotic PDF. All three putative pdf genes from L. pneumophila
      strain Philadelphia 1 have been cloned, and their encoded products have been
      overexpressed in Escherichia coli and purified. Enzymatic characterization shows
      that the purified PDFs with Ni2+ substituted are catalytically active and able to
      remove the N-formyl group from several synthetic polypeptides, although they
      appear to have different substrate specificities. Surprisingly, while PdfA and
      PdfB with Zn2+ substituted are much less active than the Ni2+ forms of each
      enzyme, PdfC with Zn2+ substituted was as active as the Ni2+ form for the fMA
      substrate and exhibited substrate specificity different from that of Ni2+ PdfC.
      Furthermore, the catalytic activities of these enzymes are potently inhibited by
      a known small-molecule PDF inhibitor, BB-3497, which also inhibits the
      extracellular growth of L. pneumophila. These results indicate that even though
      L. pneumophila has three PDFs, they can be effectively inhibited by PDF
      inhibitors which can, therefore, have potent anti-L. pneumophila activity.

PMID- 16816196
TI  - Mutational analysis of the flagellar rotor protein FliN: identification of
      surfaces important for flagellar assembly and switching.
AB  - FliN is a component of the flagellar switch complex in many bacterial species.
      The crystal structure is known for most of FliN, and a targeted cross-linking
      study (K. Paul and D. F. Blair, J. Bacteriol. 188:2502-2511, 2006) showed that it
      is organized in ring-shaped tetramers at the bottom of the basal body C ring.
      FliN is essential for flagellar assembly and direction switching, but its precise
      functions have not been defined. Here, we identify functionally important regions
      on FliN by systematic mutagenesis. Nonconservative mutations were made at
      positions sampling the surface of the protein, and the effects on flagellar
      assembly and function were measured. Flagellar assembly was disrupted by
      mutations in a conserved hydrophobic patch centered on the dimer twofold axis or
      by mutations on the surface that forms the dimer-dimer interface in the tetramer.
      The assembly defect in hydrophobic-patch mutants was partially rescued by
      overexpression of the flagellar export proteins FliH and FliI, and
      coprecipitation assays demonstrated a binding interaction between FliN and FliH
      that was weakened by mutations in the hydrophobic patch. Thus, FliN might
      contribute to export by providing binding sites for FliH or FliH-containing
      complexes. The region around the hydrophobic patch is also important for
      switching; certain mutations in or near the patch caused a smooth-swimming
      chemotaxis defect that in most cases could be partially rescued by overexpression
      of the clockwise-signaling protein CheY. The results indicate that FliN is more
      closely involved in switching than has been supposed, possibly contributing to
      the binding site for CheY on the switch.

PMID- 16816198
TI  - Alanine dehydrogenase activity is required for adequate progression of
      phycobilisome degradation during nitrogen starvation in Synechococcus elongatus
      PCC 7942.
AB  - Degradation of the cyanobacterial light-harvesting antenna, the phycobilisome, is
      a general acclimation response that is observed under various stress conditions.
      In this study we identified a novel mutant of Synechococcus elongatus PCC 7942
      that exhibits impaired phycobilisome degradation specifically during nitrogen
      starvation, unlike previously described mutants, which exhibit aberrant
      degradation under nitrogen, sulfur, and phosphorus starvation conditions. The
      phenotype of the new mutant, AldOmega, results from inactivation of ald (encoding
      alanine dehydrogenase). AldOmega is deficient in transcription induction of a
      number of genes during nitrogen starvation. These genes include the "general
      nutrient stress-related" genes, nblA and nblC, the products of which are
      essential for phycobilisome degradation. Furthermore, transcripts of several
      specific nitrogen-responsive genes accumulate at lower levels in AldOmega than in
      the wild-type strain. In contrast, ald inactivation did not decrease the
      accumulation of transcripts during sulfur starvation. Transcription of ald is
      induced upon nitrogen starvation, which is consistent with the ability of wild
      type cells to maintain a low cellular content of alanine under these conditions.
      Unlike wild-type cells, AldOmega accumulates alanine upon nitrogen starvation.
      Our analyses suggest that alanine dehydrogenase activity is necessary for an
      adequate cellular response to nitrogen starvation. Decomposition of alanine may
      be required to provide a sufficient amount of ammonia. Furthermore, the
      accumulated alanine, or a related metabolite, may interfere with the cues that
      modulate acclimation during nitrogen starvation. Taken together, our results
      provide novel information regarding cellular responses to nitrogen starvation and
      suggest that mechanisms related to nitrogen-specific responses are involved in
      modulation of a general acclimation process.

PMID- 16816199
TI  - Glycogen phosphorylase, the product of the glgP Gene, catalyzes glycogen
      breakdown by removing glucose units from the nonreducing ends in Escherichia
      coli.
AB  - To understand the biological function of bacterial glycogen phosphorylase (GlgP),
      we have produced and characterized Escherichia coli cells with null or altered
      glgP expression. glgP deletion mutants (DeltaglgP) totally lacked glycogen
      phosphorylase activity, indicating that all the enzymatic activity is dependent
      upon the glgP product. Moderate increases of glycogen phosphorylase activity were
      accompanied by marked reductions of the intracellular glycogen levels in cells
      cultured in the presence of glucose. In turn, both glycogen content and rates of
      glycogen accumulation in DeltaglgP cells were severalfold higher than those of
      wild-type cells. These defects correlated with the presence of longer external
      chains in the polysaccharide accumulated by DeltaglgP cells. The overall results
      thus show that GlgP catalyzes glycogen breakdown and affects glycogen structure
      by removing glucose units from the polysaccharide outer chains in E. coli.

PMID- 16816201
TI  - Role of DNA replication and repair in thymineless death in Escherichia coli.
AB  - Inhibition of DNA replication with hydroxyurea during thymine starvation of
      Escherichia coli shows that active DNA synthesis is not required for thymineless
      death (TLD). Hydroxyurea experiments and thymine starvation of lexA3 and uvrA DNA
      repair mutants rule out unbalanced growth, the SOS response, and nucleotide
      excision repair as explanations for TLD.

PMID- 16816200
TI  - Modulation of the ComA-dependent quorum response in Bacillus subtilis by multiple
      Rap proteins and Phr peptides.
AB  - In Bacillus subtilis, extracellular peptide signaling regulates several
      biological processes. Secreted Phr signaling peptides are imported into the cell
      and act intracellularly to antagonize the activity of regulators known as Rap
      proteins. B. subtilis encodes several Rap proteins and Phr peptides, and the
      processes regulated by many of these Rap proteins and Phr peptides are unknown.
      We used DNA microarrays to characterize the roles that several rap-phr signaling
      modules play in regulating gene expression. We found that rapK-phrK regulates the
      expression of a number of genes activated by the response regulator ComA. ComA
      activates expression of genes involved in competence development and the
      production of several secreted products. Two Phr peptides, PhrC and PhrF, were
      previously known to stimulate the activity of ComA. We assayed the roles that
      PhrC, PhrF, and PhrK play in regulating gene expression and found that these
      three peptides stimulate ComA-dependent gene expression to different levels and
      are all required for full expression of genes activated by ComA. The involvement
      of multiple Rap proteins and Phr peptides allows multiple physiological cues to
      be integrated into a regulatory network that modulates the timing and magnitude
      of the ComA response.

PMID- 16816202
TI  - Regulation of the Chlamydia trachomatis histone H1-like protein Hc2 is IspE
      dependent and IhtA independent.
AB  - The chlamydial histone-like proteins, Hc1 and Hc2, function as global regulators
      of chromatin structure and gene expression. Hc1 and Hc2 expression and activity
      are developmentally regulated. A small metabolite that disrupts Hc1 interaction
      with DNA also disrupts Hc2 interactions; however, the small regulatory RNA that
      inhibits Hc1 translation is specific to Hc1.

PMID- 16816203
TI  - Peptidoglycan structure analysis of Lactococcus lactis reveals the presence of an
      L,D-carboxypeptidase involved in peptidoglycan maturation.
AB  - Detailed structural analysis of Lactococcus lactis peptidoglycan was achieved by
      identification of its constituent muropeptides separated by reverse phase high
      performance liquid chromatography. Modification of the classical elution buffer
      allowed direct and sensitive analysis of the purified muropeptides by matrix
      assisted laser desorption ionization-time of flight mass spectrometry. The
      structures of 45 muropeptides were assigned for L. lactis strain MG1363. Analysis
      of the muropeptide composition of an MG1363 dacB mutant showed that the dacB
      encoded protein has l,d-carboxypeptidase activity and is involved in
      peptidoglycan maturation.

PMID- 16816204
TI  - Phosphate starvation induces the sporulation killing factor of Bacillus subtilis.
AB  - Bacillus subtilis produces and exports a peptide sporulation killing factor
      (SkfA) that induces lysis of sibling cells. skfA is part of the skf operon (skfA
      H), which is responsible for immunity to SkfA, as well as for production and
      export of SkfA. Here we report that transcription of skfA is markedly induced
      when cells of B. subtilis are subjected to phosphate starvation. The role of PhoP
      in regulation of the skf operon was confirmed by in vitro gel shift assays, which
      showed that this operon is a new member of the PhoP regulon. A putative stem-loop
      structure in the skfA-skfB intergenic region is proposed to act as a stabilizer
      of an skfA-specific transcript.

PMID- 16816205
TI  - Osmotic upshift transiently inhibits uptake via ABC transporters in gram-negative
      bacteria.
AB  - ATP-binding cassette transporters from several rhizobia and Salmonella enterica
      serovar Typhimurium, but not secondarily coupled systems, were inhibited by high
      concentrations (100 to 500 mM) of various osmolytes, an effect reversed by the
      removal of the osmolyte. ABC systems were also inactivated in isolated pea
      bacteroids, probably due to the obligatory use of high-osmolarity isolation
      media. Measurement of nutrient cycling in isolated pea bacteroids is impeded by
      this effect.

PMID- 16816206
TI  - Roles of the intramolecular disulfide bridge in MotX and MotY, the specific
      proteins for sodium-driven motors in Vibrio spp.
AB  - The proteins PomA, PomB, MotX, and MotY are essential for the motor function of
      Na+-driven flagella in Vibrio spp. Both MotY and MotX have the two cysteine
      residues (one of which is in a conserved tetrapeptide [CQLV]) that are inferred
      to form an intramolecular disulfide bond. The cysteine mutants of MotY prevented
      the formation of an intramolecular disulfide bond, which is presumably important
      for protein stability. Disruption of the disulfide bridge in MotX by site
      directed mutagenesis resulted in increased instability, which did not, however,
      affect the motility of the cells. These lines of evidence suggest that the
      intramolecular disulfide bonds are involved in the stability of both proteins,
      but only MotY requires the intramolecular bridge for proper function.

PMID- 16816207
TI  - Holdfast formation in motile swarmer cells optimizes surface attachment during
      Caulobacter crescentus development.
AB  - The adhesive holdfast is required for irreversible surface anchoring of
      Caulobacter crescentus cells. The holdfast is synthesized early during swarmer
      cell development and, together with pili and a functional flagellum, contributes
      to optimal attachment during cell differentiation. We present evidence that the
      timing of holdfast formation in swarmer cells is regulated posttranslationally
      and is dependent on the diguanylate cyclase PleD.

PMID- 16816208
TI  - Population structure of Francisella tularensis.
AB  - We have sequenced fragments of five metabolic housekeeping genes and two genes
      encoding outer membrane proteins from 81 isolates of Francisella tularensis,
      representing all four subspecies. Phylogenetic clustering of gene sequences from
      F. tularensis subsp. tularensis and F. tularensis subsp. holarctica aligned well
      with subspecies affiliations. In contrast, F. tularensis subsp. novicida and F.
      tularensis subsp. mediasiatica were indicated to be phylogenetically incoherent
      taxa. Incongruent gene trees and mosaic structures of housekeeping genes provided
      evidence for genetic recombination in F. tularensis.

PMID- 16816209
TI  - Regulation of the Helicobacter pylori Fe-S cluster synthesis protein NifS by
      iron, oxidative stress conditions, and fur.
AB  - Transcription of both chromosomal and extrachromosomally introduced nifS was
      regulated (up-expressed) by oxygen or by supplemental iron conditions. This up
      expression was not observed in a fur mutant strain background or when an iron
      chelator was added. Iron-bound Fur (but not apo-Fur) recognized the nifS
      promoter, and Fur bound significantly farther upstream (-155 bp to -190 bp and 
      210 to -240 bp) in the promoter than documented Helicobacter pylori Fur binding
      regions. This binding was stronger than Fur recognition of the flgE or napA
      promoter and includes a Fur recognition sequence common to the H. pylori pfr and
      sodB upstream areas. Studies of Fur-regulated genes in H. pylori have indicated
      that apo-Fur acts as a repressor, but our results demonstrate that iron-bound Fur
      activates (nifS) transcription.

PMID- 16816210
TI  - STAR*D: the results begin to roll in.

PMID- 16816211
TI  - Relationship of borderline personality disorder and bipolar disorder.

PMID- 16816212
TI  - Flying almost blind.

PMID- 16816213
TI  - Schizophrenia, antipsychotics, and the metabolic syndrome: is there a silver
      lining?

PMID- 16816214
TI  - Redefining bipolar disorder: toward DSM-V.

PMID- 16816215
TI  - Molecular determinants of energy homeostasis.

PMID- 16816216
TI  - Reflections on the relationship between psychiatric genetics and psychiatric
      nosology.
AB  - Research advances in psychiatric genetics have raised expectations that genetic
      findings might lead to major breakthroughs in psychiatric nosology. The author
      reviews the plausibility of these claims. Four areas are addressed. First, it is
      argued that familial aggregation of a single putative psychiatric syndrome
      provides at best limited evidence for the validity of that syndrome. Second, both
      traditional and molecular genetic strategies can supply important insights into
      major diagnostic conundrums. However, evidence that one or a few individual genes
      impact on risk for two disorders is not likely to resolve definitively the
      nosologic relationship between the two syndromes. Third, while gene-based
      essentialist models for psychiatric disorders are conceptually appealing, they
      are not well supported empirically. Gene discovery in psychiatry is, on its own,
      unlikely to allow us to "carve nature at its joints," thereby validating
      categorical psychiatric diagnoses. Fourth, the project to ground "messy"
      psychiatric categories on the firm foundation of genes-as an archetypal natural
      kind-may be fundamentally flawed because the very concept of "the gene" as a
      discrete entity is itself increasingly in doubt. Whereas psychiatric genetics has
      and will continue to provide important insights into the etiology of psychiatric
      and substance use disorders, it is not likely alone to provide deep answers to
      the complex and multifaceted problems facing psychiatric nosology.

PMID- 16816217
TI  - Psychotic and manic-like symptoms during stimulant treatment of attention deficit
      hyperactivity disorder.

PMID- 16816218
TI  - Persistent auditory hallucinations that are unresponsive to antipsychotic drugs.

PMID- 16816219
TI  - Depression and mania in mixed states.

PMID- 16816220
TI  - A comparison of mirtazapine and nortriptyline following two consecutive failed
      medication treatments for depressed outpatients: a STAR*D report.
AB  - OBJECTIVE: Few controlled studies have addressed the issue of which
      antidepressant medications should be recommended for outpatients who have not
      responded to multiple treatment trials. This study compared the efficacy of
      switching to mirtazapine to that of switching to a tricyclic antidepressant
      (nortriptyline) following two prospective, consecutive, unsuccessful medication
      treatments for nonpsychotic major depressive disorder. METHOD: Following lack of
      remission or an inability to tolerate an initial trial of citalopram for up to 12
      weeks (first step) and a second trial with either monotherapy involving another
      antidepressant or augmentation of citalopram with bupropion or buspirone (second
      step), adult outpatients (N=235) with nonpsychotic major depressive disorder were
      randomly assigned to 14 weeks of treatment with mirtazapine (up to 60 mg/day)
      (N=114) or nortriptyline (up to 200 mg/day) (N=121). The primary outcome, symptom
      remission, was defined a priori as a total exit score of </=7 on the 17-item
      Hamilton Rating Scale for Depression. The 16-item Quick Inventory of Depressive
      Symptomatology-Self-Report (QIDS-SR(16)), obtained at treatment visits, provided
      secondary outcomes of remission (score </=5 at exit) and response (>/=50%
      reduction in score from baseline). RESULTS: For mirtazapine, remission rates were
      12.3% and 8.0% per the Hamilton and QIDS-SR(16) scores, respectively. For
      nortriptyline, remission rates were 19.8% and 12.4%, respectively. QIDS-SR(16)
      response rates were 13.4% for mirtazapine and 16.5% for nortriptyline. Neither
      response nor remission rates statistically differed by treatment, nor did these
      two treatments differ in tolerability or adverse events. CONCLUSIONS: Switching
      to a third antidepressant monotherapy regimen after two consecutive unsuccessful
      antidepressant trials resulted in low remission rates (<20%) among patients with
      major depressive disorder.

PMID- 16816221
TI  - Descriptive and longitudinal observations on the relationship of borderline
      personality disorder and bipolar disorder.
AB  - OBJECTIVE: The purpose of this study was to test whether borderline personality
      disorder is a variant of bipolar disorder by examining the rates of co-occurrence
      in both disorders, the effects of co-occurrence on a longitudinal course, and
      whether the presence of either disorder confers the risk for new onsets of the
      other. METHOD: A prospective repeated-measures design with reliable independent
      diagnostic measures and 4 years of follow-up was used to assess 196 patients with
      borderline personality disorder and 433 patients with other personality
      disorders. RESULTS: Patients with borderline personality disorder had a
      significantly higher co-occurrence of bipolar disorder (19.4%) than did patients
      with other personality disorders. However, this co-occurrence did not appear to
      affect the subsequent course of borderline personality disorder. Although only
      8.2% of the borderline personality disorder patients developed new onsets of
      bipolar disorder, this rate was higher than in patients with other personality
      disorders. Patients with other personality disorders with co-occurring bipolar
      disorder generally had more new onsets of borderline personality disorder (25%)
      than did patients with other personality disorders without co-occurring bipolar
      disorder (10%). CONCLUSIONS: A modest association between borderline personality
      disorder and bipolar disorder is reported.

PMID- 16816222
TI  - A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the
      treatment of bipolar disorder in children and adolescents.
AB  - OBJECTIVE: This multicenter trial examined the efficacy and safety of
      oxcarbazepine in the treatment of bipolar disorder in children and adolescents.
      METHOD: A total of 116 outpatients 7 to 18 years of age with bipolar I disorder,
      manic or mixed, were recruited at 20 centers in the United States and randomly
      assigned to receive 7 weeks of double-blinded, flexibly dosed treatment with
      oxcarbazepine (maximum dose 900-2400 mg/day) or placebo. The primary efficacy
      measure was the mean change from baseline to endpoint in the Young Mania Rating
      Scale (YMRS), using the last-observation-carried-forward method. RESULTS:
      Oxcarbazepine (mean dose=1515 mg/day) did not significantly improve YMRS scores
      at endpoint compared with placebo [adjusted mean change: oxcarbazepine, -10.90
      (N=55); placebo, -9.79 (N=55)]. Dizziness, nausea, somnolence, diplopia, fatigue,
      and rash were each reported in at least 5% of the patients in the oxcarbazepine
      group with an incidence at least twice that of the placebo group. The majority of
      adverse events were mild to moderate and occurred during the titration period.
      Eleven patients (19%) in the oxcarbazepine group discontinued the study because
      of adverse events, compared with two (4%) in the placebo group. CONCLUSIONS:
      Oxcarbazepine is not significantly superior to placebo in the treatment of
      bipolar disorder in youths. While the overall adverse event profile was similar
      to that reported for patients with epilepsy, the incidence of psychiatric adverse
      events for both the oxcarbazepine and placebo groups was higher than that
      reported for the epilepsy population.

PMID- 16816224
TI  - Impact of lamotrigine and lithium on weight in obese and nonobese patients with
      bipolar I disorder.
AB  - OBJECTIVE: This study assessed weight changes in a large cohort of patients with
      bipolar disorder who were treated with randomly assigned maintenance
      monotherapies. METHOD: A post hoc analysis was conducted to assess the effects of
      lamotrigine, lithium, and placebo administration on body weight in obese and
      nonobese patients with bipolar disorder from two double-blind, placebo
      controlled, 18-month studies. RESULTS: Mean changes in weight among obese
      patients (N=155) at week 52 were -4.2, +6.1, and -0.6 kg with lamotrigine,
      lithium, and placebo, respectively (lamotrigine versus lithium and lithium versus
      placebo). Among nonobese patients (N=399), mean changes in weight (kg) at week 52
      were -0.5, +1.1, and +0.7 with lamotrigine, lithium, and placebo, respectively,
      with no significant differences among groups. CONCLUSIONS: Obese patients with
      bipolar I disorder lost weight while taking lamotrigine and gained weight while
      taking lithium.

PMID- 16816223
TI  - Changing profiles of service sectors used for mental health care in the United
      States.
AB  - OBJECTIVE: Redesigning the fragmented U.S. mental health care system requires
      knowing how service sectors share responsibility for individuals' mental health
      needs. METHOD: Twelve-month DSM-IV mental disorders and their severity were
      assessed in respondents ages 15-54 from the National Comorbidity Survey (NCS) in
      1990-1992 (N=5,388) and the NCS Replication in 2001-2003 (N=4,319). Six profiles
      involving potentially multiple service sectors were defined, including those in
      which pharmacotherapy plus psychotherapy (psychiatry profile, general medical
      with other mental health specialty profile), single modalities (general medical
      only profile, other mental health specialty only profile), or neither modality
      (human services only profile, complementary/alternative medicine only profile)
      could potentially have been received. The use of profiles was compared between
      surveys. RESULTS: The general medical only profile experienced the largest
      proportional increase (153%) between surveys and is now the most common profile.
      The psychiatry profile also increased (29%), as did the general medical with
      other mental health specialty profile (72%). The other mental health specialty
      only (-73%), the complementary/alternative medicine only (-132%), and the human
      services only (-137%) profiles all decreased in use. The elderly, women,
      minorities, the less educated, and rural dwellers were less likely to use
      profiles capable of delivering pharmacotherapies and/or psychotherapies.
      CONCLUSIONS: How service sectors share responsibility for peoples' mental health
      care is changing, with more care falling to general medical providers rather than
      specialists. Efforts are required to ensure that people who would benefit have
      access to the necessary treatment modalities.

PMID- 16816225
TI  - A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram
      treatment in drug-naive patients with obsessive-compulsive disorder.
AB  - OBJECTIVE: Reductions in the level of N-acetylaspartate within subcortical
      structures of patients with obsessive-compulsive disorder (OCD) have been
      reported in several studies. However, there have been, as yet, no reports
      regarding N-acetylaspartate levels in the prefrontal cortex of adult drug-naive
      OCD patients. The authors used proton magnetic resonance spectroscopic imaging
      ((1)H-MRSI) to investigate regional N-acetylaspartate level abnormalities and
      changes after 12 weeks of pharmacotherapy with citalopram in drug-naive OCD
      patients. METHOD: Thirteen drug-naive OCD patients and 13 age- and sex-matched
      healthy comparison subjects were included in this study. N-acetylaspartate levels
      (obtained from ratios of N-acetylaspartate with creatine, choline, and creatine
      plus choline) in the prefrontal cortex, parietal cortex, anterior cingulate,
      posterior cingulate, frontal white matter, and parietal white matter were
      measured by (1)H-MRSI. In OCD patients, measurements were taken before and after
      12 weeks of citalopram treatment. Correlations between N-acetylaspartate
      concentrations in regions of interest and clinical measures were also assessed.
      RESULTS: Drug-naive OCD patients exhibited significantly lower N-acetylaspartate
      levels in the prefrontal cortex, frontal white matter, and anterior cingulate at
      baseline than did comparison subjects. Significant increases in N-acetylaspartate
      level were detected in the prefrontal cortex and frontal white matter in OCD
      patients after 12 weeks of citalopram treatment. CONCLUSIONS: These data suggest
      that reductions in neuronal viability occur in the frontal region of OCD patients
      and that these reductions may be partly reversible.

PMID- 16816226
TI  - Family focused grief therapy: a randomized, controlled trial in palliative care
      and bereavement.
AB  - OBJECTIVE: The aim of family focused grief therapy is to reduce the morbid
      effects of grief among families at risk of poor psychosocial outcome. It
      commences during palliative care of terminally ill patients and continues into
      bereavement. The authors report a randomized, controlled trial. METHOD: Using the
      Family Relationships Index, the authors screened 257 families of patients dying
      from cancer: 183 (71%) were at risk, and 81 of those (44%) participated in the
      trial. They were randomly assigned (in a 2:1 ratio) to family focused grief
      therapy (53 families, 233 individuals) or a control condition (28 families, 130
      individuals). Assessments occurred at baseline and 6 and 13 months after the
      patient's death. The primary outcome measures were the Brief Symptom Inventory,
      Beck Depression Inventory, and Social Adjustment Scale. The Family Assessment
      Device was a secondary outcome measure. Analyses allowed for correlated family
      data and employed generalized estimating equations based on intention to treat
      and controlling for site. RESULTS: The overall impact of family focused grief
      therapy was modest, with a reduction in distress at 13 months. Significant
      improvements in distress and depression occurred among individuals with high
      baseline scores on the Brief Symptom Inventory and Beck Depression Inventory.
      Global family functioning did not change. Sullen families and those with
      intermediate functioning tended to improve overall, whereas depression was
      unchanged in hostile families. CONCLUSIONS: Family focused grief therapy has the
      potential to prevent pathological grief. Benefit is clear for intermediate and
      sullen families. Care is needed to avoid increasing conflict in hostile families.

PMID- 16816227
TI  - What happened to lithium? Antidepressant augmentation in clinical settings.
AB  - OBJECTIVE: Antidepressant augmentation is recommended when patients do not
      respond to antidepressant monotherapy. However, little is know about
      antidepressant augmentation in clinical settings and whether these practices
      reflect the research evidence. METHOD: The authors identified 244,859 patients in
      Veterans Administration mental health settings with a diagnosis of depression and
      an antidepressant prescription during fiscal year 2002. Patients with
      schizophrenia, dementia, or bipolar I disorder were excluded. The authors
      examined the prevalence and characteristics of antidepressant augmentation during
      the year, defined as receiving an antidepressant and an augmenting agent
      (lithium, second-generation antipsychotics, combinations of antidepressants,
      anticonvulsants, or "other") for >/=60 consecutive days in specified doses for
      those without other clinical indications. Mixed-effect models were used to
      examine predictors of augmentation. RESULTS: Some patients (22%) received an
      augmenting agent. The most commonly used agents were a second antidepressant
      (11%) and a second-generation antipsychotic (7%). Only 0.5% of the patients
      received lithium. Whites, younger patients, and those with a prior
      hospitalization were more likely to receive augmentation. African Americans were
      more likely to receive antipsychotic augmentation; whites were more likely to
      receive lithium. CONCLUSIONS: Antidepressant augmentation is common in clinical
      settings. Although lithium currently has the most research support, antipsychotic
      medications and a second antidepressant are the most widely used augmenting
      agents. Many augmenting agents are used across clinical and demographic groups.
      Research is needed on the relative effectiveness of these agents, along with
      efforts to promote the use of agents with the greatest level of research support.

PMID- 16816228
TI  - Adolescent suicidal ideation as predictive of psychopathology, suicidal behavior,
      and compromised functioning at age 30.
AB  - OBJECTIVE: The purpose of this study was to examine whether suicidal ideation in
      a community population of adolescents represents normative adolescent angst or is
      predictive of psychopathology, suicidal and problem behaviors, and compromised
      functioning 15 years after onset. METHOD: Participants were 346 largely Caucasian
      individuals who were part of a single-age cohort from a working class community
      and whose development had been traced prospectively from ages 5 to 30. Those with
      suicidal ideation at age 15 were compared to those without suicidal ideation at
      age 15 on measures of psychopathology, suicidal ideation and behavior, problem
      behaviors, and adult functioning at age 30. Gender differences were assessed
      across all domains. RESULTS: At age 30, there were marked differences between
      adolescents with suicidal ideation and adolescents without suicidal ideation of
      both genders in most domains examined. Subjects with suicidal ideation were twice
      as likely to have an axis I disorder, nearly 12 times more likely to have
      attempted suicide by age 30, and 15 times more likely to have expressed suicidal
      thoughts in the past 4 years. Subjects with suicidal ideation had more problem
      behaviors and poorer overall functioning as assessed by multiple informants.
      Their self-perceptions of coping ability, self-esteem, and interpersonal
      relations were also lower. Although subjects with suicidal ideation among both
      genders had higher levels of psychopathology, suicidal ideation and behavior, and
      problem behaviors at age 30, male subjects with suicidal ideation had lower
      salaries and socioeconomic status and were less likely to have achieved
      residential independence. CONCLUSIONS: Findings underscore the importance of
      considering suicidal ideation in adolescence as a marker of severe distress and a
      predictor of compromised functioning, indicating the need for early
      identification and continued intervention.

PMID- 16816229
TI  - The availability of web sites offering to sell opioid medications without
      prescriptions.
AB  - OBJECTIVE: This study was designed to determine the availability of web sites
      offering to sell opioid medications without prescriptions. METHOD: Forty-seven
      Internet searches were conducted with a variety of opioid medication terms,
      including "codeine," "no prescription Vicodin," and "OxyContin." Two independent
      raters examined the links generated in each search and resolved any coding
      disagreements. The resulting links were coded as "no prescription web sites"
      (NPWs) if they offered to sell opioid medications without prescriptions. RESULTS:
      In searches with terms such as "no prescription codeine" and "Vicodin," over 50%
      of the links obtained were coded as "NPWs." The proportion of links yielding NPWs
      was greater when the phrase "no prescription" was added to the opioid term. More
      than 300 opioid NPWs were identified and entered into a database. CONCLUSIONS:
      Three national drug-use monitoring studies have cited significant increases in
      prescription opioid use over the past 5 years, particularly among young people.
      The emergence of NPWs introduces a new vector for unregulated access to opioids.
      Research is needed to determine the effect of NPWs on prescription opioid use
      initiation, misuse, and dependence.

PMID- 16816230
TI  - The impact of ADHD and autism spectrum disorders on temperament, character, and
      personality development.
AB  - OBJECTIVE: The authors describe personality development and disorders in relation
      to symptoms of attention deficit hyperactivity disorder (ADHD) and autism
      spectrum disorders. METHOD: Consecutive adults referred for neuropsychiatric
      investigation (N=240) were assessed for current and lifetime ADHD and autism
      spectrum disorders and completed the Temperament and Character Inventory. In a
      subgroup of subjects (N=174), presence of axis II personality disorders was also
      assessed with the Structured Clinical Interview for DSM-IV Personality Disorders
      (SCID-II). RESULTS: Patients with ADHD reported high novelty seeking and high
      harm avoidance. Patients with autism spectrum disorders reported low novelty
      seeking, low reward dependence, and high harm avoidance. Character scores (self
      directedness and cooperativeness) were extremely low among subjects with
      neuropsychiatric disorders, indicating a high overall prevalence of personality
      disorders, which was confirmed with the SCID-II. Cluster B personality disorders
      were more common in subjects with ADHD, while cluster A and C disorders were more
      common in those with autism spectrum disorders. The overlap between DSM-IV
      personality disorder categories was high, and they seem less clinically useful in
      this context. CONCLUSIONS: ADHD and autism spectrum disorders are associated with
      specific temperament configurations and an increased risk of personality
      disorders and deficits in character maturation.

PMID- 16816231
TI  - A validation of event-related FMRI comparisons between users of cocaine,
      nicotine, or cannabis and control subjects.
AB  - OBJECTIVE: Noninvasive brain imaging techniques are a powerful tool for
      researching the effects of drug abuse on brain activation measures. However,
      because many drugs have direct vascular effects, the validity of techniques that
      depend on blood flow measures as a reflection of neuronal activity may be called
      into question. This may be of particular concern in event-related functional
      magnetic resonance imaging (fMRI), where current analytic techniques search for a
      specific shape in the hemodynamic response to neuronal activity. METHOD: To
      investigate possible alterations in task-related activation as a result of drug
      abuse, fMRI scans were conducted on subjects in four groups as they performed a
      simple event-related finger-tapping task: users of cocaine, nicotine, or cannabis
      and control subjects. RESULTS: Activation measures, as determined by two
      different analytic methods, did not differ between the groups. A comparison
      between an intravenous saline and an intravenous cocaine condition in cocaine
      users found a similar null result. Further in-depth analyses of the shape of the
      hemodynamic responses in each group also showed no differences. CONCLUSIONS: This
      study demonstrates that drug groups may be compared with control subjects using
      event-related fMRI without the need for any post hoc procedures to correct for
      possible drug-induced cardiovascular alterations. Thus, fMRI activation
      differences reported between these drug groups can be more confidently
      interpreted as reflecting neuronal differences.

PMID- 16816232
TI  - Volumetric analysis and three-dimensional glucose metabolic mapping of the
      striatum and thalamus in patients with autism spectrum disorders.
AB  - OBJECTIVE: In patients with autism, behavioral deficits as well as neuroimaging
      studies of the anterior cingulate cortex suggest ventral rather than dorsal
      striatal and thalamic abnormalities in structure and function. The authors used
      imaging studies to map volumetric and metabolic differences within the entire
      dorsoventral extent of the striatum and thalamus. METHOD: Magnetic resonance
      imaging (MRI) and positron emission tomography (PET) were used to measure volumes
      and metabolic activity in the thalamus, caudate, and putamen in 17 patients with
      autism or Asperger's disorder and 17 age- and sex-matched comparison subjects.
      Subjects performed a serial verbal learning test during the [(18)F]
      fluorodeoxyglucose uptake period. The regions of interest were outlined on
      contiguous axial MRI slices. After PET/MRI coregistration, region-of-interest
      coordinates were applied to the PET scan for each individual. Between-group
      differences in metabolism were assessed by three-dimensional statistical
      probability mapping. RESULTS: The patients with autism spectrum disorders had
      greater volumes of the right caudate nucleus than comparison subjects as well as
      a reversal of the expected left-greater-than-right hemispheric asymmetry.
      Patients also had lower relative glucose metabolic rates bilaterally in the
      ventral caudate, putamen, and thalamus. Patients with autism had lower metabolic
      activity in the ventral thalamus than those with Asperger's disorder, but they
      did not differ from comparison subjects in metabolic activity in the caudate
      nucleus. CONCLUSIONS: These results are consistent with a deficit in the anterior
      cingulate-ventral striatum-anterior thalamic pathway in patients with autism
      spectrum disorders. The results also suggest an important role for the caudate in
      helping support working-memory demands.

PMID- 16816234
TI  - Prevalence of the metabolic syndrome among patients receiving clozapine.
AB  - OBJECTIVE: This study compared the prevalence of the metabolic syndrome among
      outpatients with schizophrenia and schizoaffective disorder receiving clozapine
      with a matched comparison group from the National Health and Nutrition
      Examination Survey. METHOD: Ninety-three outpatients and a matched group of 2,701
      comparison subjects were compared according to National Cholesterol Education
      Program criteria. Outpatient data were obtained through physical assessments,
      laboratory testing, and reviews of medical records. RESULTS: The prevalence of
      the metabolic syndrome was significantly higher among clozapine patients (53.8%)
      than among the comparison group (20.7%). For clozapine patients, logistic
      regression analysis revealed significant associations with age, body mass index,
      and duration of clozapine treatment. Only age and body mass index were associated
      with the prevalence of metabolic syndrome in both groups. CONCLUSIONS: Patients
      receiving clozapine are at significantly increased risk for developing the
      metabolic syndrome. Psychiatrists and other providers should consider performing
      regular physical health monitoring to prevent long-term adverse health
      consequences.

PMID- 16816233
TI  - Ferritin levels and their association with regional brain volumes in Tourette's
      syndrome.
AB  - OBJECTIVE: A previous small study showed lower serum ferritin levels in subjects
      with Tourette's syndrome than in healthy subjects. The authors measured
      peripheral iron indices in a large group of Tourette's syndrome and comparison
      subjects and explored associations of ferritin levels with regional brain
      volumes. METHOD: Ferritin was measured in 107 children and adults (63 Tourette's
      syndrome, 44 comparison); serum iron was measured in 73 (41 Tourette's syndrome,
      32 comparison). Magnetic resonance imaging scans were used to measure volumes of
      the basal ganglia and cortical gray matter. RESULTS: Ferritin and serum iron were
      significantly lower in the Tourette's syndrome subjects, although still within
      the normal range. No association was found between tic severity and either iron
      index. In the Tourette's syndrome subjects, ferritin did not correlate
      significantly with caudate volume but did correlate positively with putamen
      volume. In the comparison subjects, ferritin correlated inversely with caudate
      volume but did not correlate significantly with putamen volume. Irrespective of
      diagnosis, ferritin correlated positively with volumes of the sensorimotor,
      midtemporal, and subgenual cortices. CONCLUSIONS: The lower peripheral ferritin
      and iron levels in persons with Tourette's syndrome are consistent with findings
      in other movement disorders and suggest that lower iron availability may have a
      causal role in the pathophysiology of tic disorders. Lower iron stores may
      contribute to hypoplasia of the caudate and putamen, increasing vulnerability to
      developing tics or to having more severe tics. Lower iron stores may also
      contribute to smaller cortical volumes and consequently to reduced inhibitory
      control of tics.

PMID- 16816235
TI  - Association of initial antipsychotic response to clozapine and long-term weight
      gain.
AB  - OBJECTIVE: The aim of this study was to test whether the initial antipsychotic
      response to clozapine is related to subsequent weight change. METHOD: This study
      was an 8-year retrospective chart review of 96 hospitalized patients with
      schizophrenia. Data on monthly weight change, initial clinical response, age,
      gender, clozapine dose, and concomitant use of mood stabilizers and other
      antipsychotics were analyzed. RESULTS: Fifty-five (57.3%) of the patients
      received clozapine over the entire 8-year period; these subjects experienced an
      average weight gain of 11.7 kg (SD=1.6). Seventeen of these patients (30.9%) who
      had a significant initial clinical response (CGI improvement rating of 1 or 2
      during the first 14 months) gained significantly more weight (13.8 kg [SD=8.4])
      than did the 38 patients without a significant initial response (4.5 kg
      [SD=12.0]). Multiple linear regression analysis showed significant initial
      clinical response and lower baseline body mass index were associated with
      significantly more weight gain. CONCLUSIONS: The results show that initial
      antipsychotic response to clozapine is associated with subsequent long-term
      weight gain as measured over 8 years.

PMID- 16816236
TI  - Suicidality in body dysmorphic disorder: a prospective study.
AB  - OBJECTIVE: Cross-sectional/retrospective data have indicated that individuals
      with body dysmorphic disorder (BDD) have high rates of suicidal ideation and
      attempts. However, no study, to the authors' knowledge, has prospectively
      examined suicidality in BDD. METHOD: In the first prospective study of BDD's
      course, the authors examined suicidality in 185 subjects for up to 4 years.
      RESULTS: Suicidal ideation was reported by a mean of 57.8% of the subjects per
      year, and a mean of 2.6% attempted suicide per year. Two subjects (0.3% per year)
      completed suicide. CONCLUSIONS: Individuals with BDD have high rates of suicidal
      ideation and attempts. The completed suicide rate is preliminary but suggests
      that the rate of completed suicide in BDD is markedly high.

PMID- 16816237
TI  - Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and
      trichotillomania.
AB  - OBJECTIVE: Problems with inhibiting certain pathological behaviors are integral
      to obsessive-compulsive disorder (OCD), trichotillomania, and other putative
      obsessive-compulsive spectrum disorders. The authors assessed and compared motor
      inhibition and cognitive flexibility in OCD and trichotillomania for the first
      time, to their knowledge. METHOD: The Stop-Signal Task and the
      Intradimensiona/Extradimensional Shift Task were administered to 20 patients with
      OCD, 17 patients with trichotillomania, and 20 healthy comparison subjects.
      RESULTS: Both OCD and trichotillomania showed impaired inhibition of motor
      responses. For trichotillomania, the deficit was worse than for OCD, and the
      degree of the deficit correlated significantly with symptom severity. Only
      patients with OCD showed deficits in cognitive flexibility. CONCLUSIONS: Impaired
      inhibition of motor responses (impulsivity) was found in OCD and
      trichotillomania, whereas cognitive inflexibility (thought to contribute to
      compulsivity) was limited to OCD. This assessment will advance the
      characterization and classification of obsessive-compulsive spectrum disorders
      and aid the development of novel treatments.

PMID- 16816238
TI  - Clinical assessment of pathological personality traits.
AB  - OBJECTIVE: Research has raised questions about the ability of clinicians to make
      reliable diagnostic judgments about personality. The aim of this study was to
      assess the reliability and validity of the dimensional diagnosis of pathological
      personality traits with the Shedler-Westen Assessment Procedure-200 (SWAP-200) Q
      sort. METHOD: Two clinician/judges independently described 24 outpatients using
      the SWAP-200, based on a systematic clinical interview. Treating clinicians
      described the patients using the SWAP-200 based on their knowledge of the
      patients over the course of treatment while they were blind to interview data.
      RESULTS: Interrater reliability was high. Convergent and discriminant validity
      between interviewers and clinicians was also strong. A procedure recently
      developed for providing precise estimates of construct validity with contrast
      analysis applied to correlational data documented strong evidence of validity.
      CONCLUSIONS: Clinicians and independent interviewers can reliably assess complex
      personality traits associated with personality pathology using the SWAP-200.

PMID- 16816239
TI  - Effects of season of birth on autism spectrum disorders: fact or fiction?
AB  - OBJECTIVE: This study attempted to examine the relationship between month and
      season of birth and risk for autism spectrum disorders. METHOD: The cohort
      included all Jewish individuals born in Israel over 5 consecutive years
      (N=311,169) and assessed by the Israeli Draft Board as part of the mandatory
      assessment of eligibility for military service conducted at age 17. The outcome
      of autism spectrum disorders was ascertained from the Draft Board Medical
      Registry, which contains information about medical and psychiatric disorders for
      this population of adolescents. RESULTS: There was no association between month
      or season of birth and the prevalence of autistic spectrum disorders.
      CONCLUSIONS: The findings from this historical, population-based cohort study do
      not support an association between season of birth and autistic spectrum
      disorders.

PMID- 16816240
TI  - An MRI study of increased cortical thickness in autism.
AB  - OBJECTIVE: The purpose of this study was to examine cortical thickness in autism
      in light of the postmortem evidence of cortical abnormalities of the disorder.
      METHOD: Magnetic resonance imaging (MRI) scans were acquired from 17 children
      with autism and 14 healthy comparison subjects, and sulcal and gyral thickness
      were measured for the total brain and for all lobes. RESULTS: Increases in total
      cerebral sulcal and gyral thickness were observed in children with autism
      relative to comparison subjects. Similar findings were noted in the temporal and
      parietal lobes but not in the frontal and occipital lobes. CONCLUSIONS: These
      preliminary findings indicate that increased cortical thickness may contribute to
      the increased gray matter volume and total brain size that have been observed in
      autism and may also be related to anomalies in cortical connectivity.

PMID- 16816241
TI  - Remission rates for depression in STAR*D study.

PMID- 16816242
TI  - Over-optimism of cognitive behavior therapy for schizophrenia.

PMID- 16816243
TI  - Do symptom dimensions of depression following myocardial infarction relate
      differently to physical health indicators and cardiac prognosis?

PMID- 16816244
TI  - Blinding in psychotherapy plus medication trials.

PMID- 16816246
TI  - Gambling-related problems are chronic and persist for the majority of individuals
      with a lifetime diagnosis of pathological gambling.

PMID- 16816247
TI  - Reversible neutropenia with olanzapine following clozapine-induced neutropenia.

PMID- 16816248
TI  - Opiate treatment for patients in chronic non-cancer pain.

PMID- 16816249
TI  - Journals join the podcast revolution.

PMID- 16816250
TI  - Better research for better healthcare.

PMID- 16816251
TI  - Gym users and abuse of prescription drugs.

PMID- 16816252
TI  - Miss, Mister, Doctor. Distinguishing titles.

PMID- 16816253
TI  - Miss, Mister, Doctor. My surgeon's name is...

PMID- 16816254
TI  - Miss, Mister, Doctor. How we are titled is of little consequence.

PMID- 16816255
TI  - Miss, Mister, Doctor. Do surgeons wish to become doctors?

PMID- 16816256
TI  - Miss, Mister, Doctor. Doctor or Mister?

PMID- 16816257
TI  - Miss, Mister, Doctor. To protect and serve the patient.

PMID- 16816258
TI  - Miss, Mister, Doctor. An insult.

PMID- 16816259
TI  - Miss, Mister, Doctor. Preferred titles.

PMID- 16816260
TI  - Miss, Mister, Doctor. Puzzling titles.

PMID- 16816261
TI  - Celecoxib.

PMID- 16816262
TI  - From optimism to disillusion about commitment to transparency in the medico
      industrial complex.

PMID- 16816263
TI  - 'Dottyville'--Craiglockhart War Hospital and shell-shock treatment in the First
      World War.

PMID- 16816264
TI  - Medical journals and the mass media: moving from love and hate to love.

PMID- 16816265
TI  - Viral hepatitis B and C in children.

PMID- 16816266
TI  - Ambulatory antibiotic prescribing for acute bronchitis and cough and hospital
      admissions for respiratory infections: time trends analysis.
AB  - OBJECTIVES: To examine the relationship between ambulatory antibiotic prescribing
      for acute bronchitis and cough with hospital admissions for respiratory
      infections in the USA between 1996 and 2003. DESIGN: Analysis of data on
      antibiotic prescribing for episodes of acute bronchitis/cough illness in
      ambulatory care and hospitalization for respiratory infections for adults between
      1996 and 2003 in the USA. SETTING: USA: ambulatory prescribing behaviour was
      derived from the National Ambulatory Medical Care Survey and the National
      Hospital Ambulatory Medical Care Survey while hospitalizations in acute care
      hospitals were assessed in the National Hospital Discharge Survey. PARTICIPANTS:
      Adults 18-64 years old. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Proportion of
      visits for acute bronchitis/cough receiving a prescription for antibiotics and
      hospitalization for respiratory infections. RESULTS: Ambulatory antibiotic
      prescribing practices for acute bronchitis/cough and hospitalizations for
      respiratory infections exhibited non-linear patterns over the 8 year period.
      However, antibiotic prescribing practices for acute bronchitis/cough and
      hospitalizations for respiratory infections had a weak/moderate negative
      association. For three of the seven yearly changes in prescribing and
      hospitalizations as one increased the other decreased (P<0.01). CONCLUSIONS:
      Ambulatory antibiotic prescribing for respiratory tract infections was inversely
      associated with hospital admissions for respiratory tract infections.

PMID- 16816267
TI  - Exercise-associated hyponatraemia after a marathon: case series.
AB  - OBJECTIVES: To review the presentation, treatment and response of those runners
      from the London Marathon who presented to St Thomas' Hospital with exercise
      induced hyponatraemia. DESIGN: Observational case series. SETTING: St Thomas'
      Hospital, a tertiary hospital situated near the finish line of the 2003 London
      Marathon. PARTICIPANTS: All runners who presented to St Thomas' Hospital on the
      day of the 2003 London Marathon with altered mental state whose serum sodium
      concentration was less than 135 mmol/L. MAIN OUTCOME MEASURES: Presenting
      symptoms, volume and type of fluids administered and response to treatment
      (biochemical and clinical). RESULTS: Fourteen patients were diagnosed with
      exercise associated hyponatraemia with serum sodium concentrations ranging from
      116 to 133 mmol/L. Eleven presented with confusion. There were long delays
      between the finish time and presentation time for some runners. Anecdotal
      descriptions suggested some runners finished the race with normal mental state
      then became confused. There was no correlation between running time and serum
      sodium level. All patients received 0.9% saline and six received 1.8% saline.
      Despite this, some patients demonstrated falls in serum sodium concentrations.
      Thirteen to fourteen patients were symptomatically well the following morning,
      with the remaining patient significantly improved. CONCLUSION: Presentation of
      exercise associated hyponatraemia may be delayed. Optimal treatment is
      controversial, but the use of isotonic saline may not result in rises of serum
      sodium and we would suggest the early use of hypertonic fluids in symptomatic
      patients.

PMID- 16816268
TI  - Spinal abscess and mitral valve endocarditis secondary to asymptomatic
      fusobacterium-induced dental abscess.

PMID- 16816269
TI  - Trigger thumb in a fish-owner.

PMID- 16816270
TI  - Syphilis presenting as acute multifocal retino-choroiditis.

PMID- 16816271
TI  - 'An innocent deception': placebo controls in the St Petersburg homeopathy trial,
      1829-1830.

PMID- 16816272
TI  - A retrospectroscopic overview of political/administrative intrusion--is a
      'patients' revolt' not now indicated?

PMID- 16816274
TI  - The integration-fragmentation paradox.

PMID- 16816275
TI  - Law & psychiatry: "depressed? Get out!": dealing with suicidal students on
      college campuses.
AB  - This column examines college and university policies under which students who
      manifest suicidal ideation are barred from campus, usually by immediate
      suspension or mandatory withdrawal. Such policies, which appear to be increasing
      on U.S. campuses, generally reflect administrators' fears of legal liability if
      students commit suicide on campus. The author reviews two recent cases-Schieszler
      v. Ferrum College and Shin v. Massachusetts Institute of Technology-that have
      created a climate of fear among administrators and suggests ways to change
      blanket policies so that students at low risk of suicide will not be barred from
      campus and will seek and obtain appropriate treatment.

PMID- 16816276
TI  - Collaborative care for bipolar disorder: part I. Intervention and implementation
      in a randomized effectiveness trial.
AB  - Outcome for bipolar disorder remains suboptimal despite the availability of
      efficacious treatments. To improve treatment effectiveness in clinical practice,
      a Veterans Affairs study team created a care model conceptually similar to the
      lithium clinics of the 1970s but augmented by principles of more recent
      collaborative care models for chronic medical illnesses. This intervention
      consists of improving patients' self-management skills through psychoeducation;
      supporting providers' decision making through simplified practice guidelines; and
      enhancing access to care, continuity of care, and information flow through the
      use of a nurse care coordinator. In this article, which is part I of a two-part
      report, the authors summarize the conceptual background and development of the
      intervention, describe the design of a three-year, 11-site randomized
      effectiveness trial, and report data describing its successful implementation.
      Trial design emphasized aspects of effectiveness to support generalizability of
      the findings and eventual dissemination of the intervention. Part II (see
      companion article, this issue) reports clinical, functional, and overall cost
      outcomes of the trial.

PMID- 16816277
TI  - Collaborative care for bipolar disorder: Part II. Impact on clinical outcome,
      function, and costs.
AB  - OBJECTIVE: The study addressed whether a collaborative model for chronic care,
      described in part I (this issue), improves outcome for bipolar disorder. METHODS:
      The intervention was designed to improve outcome by enhancing patient self
      management skills with group psychoeducation; providing clinician decision
      support with simplified practice guidelines; and improving access to care,
      continuity of care, and information flow via nurse care coordinators. In an
      effectiveness design veterans with bipolar disorder at 11 Veterans Affairs
      hospitals were randomly assigned to three years of care in the intervention or
      continued usual care. Blinded clinical and functional measures were obtained
      every eight weeks. Intention-to-treat analysis (N=306) with mixed-effects models
      addressed the hypothesis that improvements would accrue over three years,
      consistent with social learning theory. RESULTS: The intervention significantly
      reduced weeks in affective episode, primarily mania. Broad-based improvements
      were demonstrated in social role function, mental quality of life, and treatment
      satisfaction. Reductions in mean manic and depressive symptoms were not
      significant. The intervention was cost-neutral while achieving a net reduction of
      6.2 weeks in affective episode. CONCLUSIONS: Collaborative chronic care models
      can improve some long-term clinical outcomes for bipolar disorder. Functional and
      quality-of-life benefits also were demonstrated, with most benefits accruing in
      years 2 and 3.

PMID- 16816278
TI  - PRISM-E: comparison of integrated care and enhanced specialty referral models in
      depression outcomes.
AB  - OBJECTIVE: This study, entitled Primary Care Research in Substance Abuse and
      Mental Health for the Elderly, examined six-month outcomes for older primary care
      patients with depression who received different models of treatment. METHODS:
      Clinical outcomes were compared for patients who were randomly assigned to
      integrated care or enhanced specialty referral. Integrated care consisted of
      mental health services co-located in primary care in collaboration with primary
      care physicians. Enhanced specialty referral consisted of referral to physically
      separate, clearly identified mental health or substance abuse clinics. RESULTS: A
      total of 1,531 patients were included; their mean age was 73.9 years. Remission
      rates and symptom reduction for all depressive disorders were similar for the two
      models at the three- and six-month follow-ups. For the subgroup with major
      depression, the enhanced specialty referral model was associated with a greater
      reduction in depression severity than integrated care, but rates of remission and
      change in function did not differ across models of care for major depression.
      CONCLUSIONS: Six-month outcomes were comparable for the two models. For the
      subgroup with major depression, reduction in symptom severity was superior for
      those randomly assigned to the enhanced specialty referral group.

PMID- 16816279
TI  - PRISM-E: comparison of integrated care and enhanced specialty referral in
      managing at-risk alcohol use.
AB  - OBJECTIVE: This study was part of the Primary Care Research in Substance Abuse
      and Mental Health for the Elderly study (PRISM-E) and determined the relative
      effectiveness of two different models of care for reducing at-risk alcohol use
      among primary care patients aged 65 and older. METHODS: This multisite study was
      a randomized clinical trial comparing integrated care with enhanced specialty
      referral for older primary care patients screened and identified to have at-risk
      drinking. RESULTS: Before the study, the 560 participants consumed a mean of 17.9
      drinks per week and had a mean of 21.1 binge episodes in the prior three months.
      At six months, both treatment groups reported lower levels of average weekly
      drinking (p<.001) and binge drinking (p<.001), despite low levels of treatment
      engagement. However, the declines did not differ significantly between treatment
      groups. CONCLUSIONS: These results suggest that older persons with at-risk
      drinking can substantially modify their drinking over time. Although no evidence
      suggested that the model of care was important in achieving this result, the
      magnitude of reduction in alcohol use was comparable with other intervention
      studies.

PMID- 16816280
TI  - Psychotherapy, symptom outcomes, and role functioning over one year among
      patients with bipolar disorder.
AB  - OBJECTIVE: Randomized trials indicate that psychosocial interventions effective
      adjuncts to pharmacotherapy in bipolar disorder (1,2). A one-year naturalistic
      prospective design was used to examine the association between psychotherapy use
      and the symptomatic and functional outcomes of patients with bipolar disorder.
      METHODS: Patients with bipolar disorder in a depressed phase (N=248) were drawn
      from the first 1,000 enrollees (November 1999 to April 2002) in the Systematic
      Treatment Enhancement Program (STEP-BD), a study of patients with bipolar
      disorder receiving best-practice pharmacotherapy. Patients were seen clinics and
      interviewed every three months over one year regarding of psychotherapy services,
      symptoms, and role functioning. Mixed-effects regression models were used to
      examine whether the amount of psychotherapy the patients received during each
      three-month interval was associated with symptomatic or psychosocial functioning
      during the same or a subsequent three-month interval. RESULTS: During the study
      year, percent of the patients had at least one psychotherapy session. Among
      patients who began an interval with severe depressive symptoms or low
      functioning, having more frequent sessions of psychotherapy was associated with
      less severe mood symptoms and better functioning in the same or a subsequent
      study interval. In contrast, among patients who began interval with less severe
      depressive symptoms or higher functioning, fewer psychotherapy sessions were
      associated with less severe depressive symptoms and greater functioning in the
      same or a subsequent interval. CONCLUSIONS: Intensive psychotherapy may be most
      applicable to severely ill patients with bipolar disorder, whereas briefer
      treatments may be adequate for less severely ill patients.

PMID- 16816281
TI  - Use of outpatient mental health services by depressed and anxious children as
      they grow up.
AB  - OBJECTIVE: Childhood-onset psychiatric disorders can be persistent and impairing
      but often go untreated. Affected individuals' treatment utilization into
      adulthood is not well understood. A 15-year follow-up of depressed, anxious, and
      never mentally ill children (control group) examined need, predisposing, and
      enabling factors associated with use of outpatient mental health care into early
      adulthood. METHODS: Between 1977 and 1985, a total of 315 children and
      adolescents were ascertained. Their psychiatric status and treatment utilization
      into adulthood were reassessed between 1991 and 1997 by clinicians blind to their
      childhood diagnoses. RESULTS: Respondents ascertained for depression demonstrated
      13-fold, and those ascertained for anxiety demonstrated six-fold, greater odds of
      any treatment compared with controls. Among utilizers, childhood depression
      conferred 14-fold, and childhood anxiety, 23-fold, increased odds of long-term
      treatment. Blacks were less likely than whites to obtain treatment. Utilizers
      older at follow-up reported longer treatment duration. Mood disorder episodes
      over follow-up and poorer global functioning were associated with both increased
      odds of any utilization and increased treatment duration among utilizers.
      CONCLUSIONS: This sample demonstrated high and persistent treatment utilization.
      Need indicated by childhood diagnosis was the strongest predictor of treatment;
      however, utilization also differed by race or ethnicity. Strategies to maximize
      the uptake of effective, culturally relevant treatment approaches should be
      investigated.

PMID- 16816282
TI  - Using the PHQ-9 for depression screening and treatment monitoring for Chinese
      Americans in primary care.
AB  - OBJECTIVE: Because Chinese Americans are known to underutilize mental health
      services, routine screening for depression in primary care clinics has been
      advocated as a means of identifying Chinese-American patients with depression and
      initiating appropriate treatment. This analysis evaluated the utility of the nine
      item depression module of the Patient Health Questionnaire (PHQ-9) for depression
      screening and monitoring treatment outcomes among Chinese Americans at a primary
      health care setting. METHODS: A total of 3,417 patients who presented for an
      initial or annual physical examination with their primary care providers were
      screened for depression between January and October 2003 at the Charles B. Wang
      Community Health Center, a primary health care center in New York City serving
      primarily low-income Chinese Americans. The depression screen was a two-tier
      process: if patients endorsed one or more of three initial questions on an
      abridged version of the PHQ-9, they were then administered the PHQ-9. RESULTS: A
      total of 141 individuals (4.1 percent) had clinically significant depressive
      symptoms (PHQ-9 score of 10 or higher). Women were more likely to have
      significant levels of depressive symptoms than men (17.3 percent compared with
      11.6 percent). A total of 114 of the 141 patients with clinically significant
      depressive symptoms received treatment plans initiated by their primary care
      provider. Forty (35.1 percent) responded to treatment (50 percent decrease in PHQ
      9 score) by eight weeks of treatment. CONCLUSIONS: The PHQ-9 can be used to
      screen for depression as well as guide depression treatment planning among
      Chinese Americans in primary care. Screening for major depression with the PHQ-9
      in primary care settings should be considered for appropriate identification and
      treatment of depression for Chinese-American patients.

PMID- 16816283
TI  - Tenant outcomes in supported housing and community residences in New York City.
AB  - OBJECTIVE: This study examined whether outcomes in housing, clinical status, and
      well-being of persons with severe mental illness and a history of homelessness
      differ between those in supported housing and those in community residences, two
      housing arrangements that substantially differ in the level of independence that
      is offered to its tenants. METHODS: A quasi-experimental 18-month follow-up study
      was conducted with 157 persons newly entering supported housing and community
      residences. The housing models accepted persons with similar illness
      characteristics and homelessness histories, so that the inability to randomly
      assign tenants to housing types could be compensated for by propensity scoring
      methods. Tenure in housing was examined by using survival models. Analyses of
      other outcomes used hierarchical linear and regression models in both intent-to
      treat (N=139) and true-stayer (N=80) analyses. RESULTS: Tenure in housing did not
      differ by housing type. Substantial proportions of tenants in both models
      remained housed during the follow-up period. Tenants in supported housing
      reported greater housing satisfaction in terms of autonomy and economic
      viability. Over time some tenants in supported housing reported greater feelings
      of isolation. Independent of housing type, symptoms of depression or anxiety at
      housing entry increased the risk of poorer outcomes. CONCLUSIONS: The models of
      supported housing were viable portals of entry into community housing for
      homeless persons, even for consumers with characteristics indicating that they
      would have been more likely to be placed in community residences. The results
      suggest that greater clinical attention should be paid to persons who exhibit
      depression or anxiety when entering housing.

PMID- 16816284
TI  - Impact of permanent supportive housing on the use of acute care health services
      by homeless adults.
AB  - OBJECTIVE: This analysis examined the impact of permanent supportive housing on
      the use of acute care public health services by homeless people with mental
      illness, substance use disorder, and other disabilities. METHODS: The sample
      consisted of 236 single adults who entered supportive housing at two San
      Francisco sites, Canon Kip Community House and the Lyric Hotel, between October
      10, 1994, and June 30, 1998. Eighty percent had a diagnosis of dual psychiatric
      and substance use disorders. Administrative data from the city's public health
      system were used to construct a retrospective, longitudinal history of service
      use. Analyses compared service use during the two years before entry into
      supportive housing with service use during the two years after entry. RESULTS:
      Eighty-one percent of residents remained in permanent supportive housing for at
      least one year. Housing placement significantly reduced the percentage of
      residents with an emergency department visit (53 to 37 percent), the average
      number of visits per person (1.94 to .86), and the total number of emergency
      department visits (56 percent decrease, from 457 to 202) for the sample as a
      whole. For hospitalizations, permanent supportive housing placement significantly
      reduced the likelihood of being hospitalized (19 to 11 percent) and the mean
      number of admissions per person (.34 to .19 admissions per resident).
      CONCLUSIONS: Providing permanent supportive housing to homeless people with
      psychiatric and substance use disorders reduced their use of costly hospital
      emergency department and inpatient services, which are publicly provided.

PMID- 16816285
TI  - Managing Medicaid behavioral health care: findings of a national survey in the
      year 2000.
AB  - OBJECTIVE: Although Medicaid is the primary payer for public mental health
      systems, relatively little is known about managed care arrangements at the health
      plan level. METHODS: A brief cross-sectional survey was customized for each of
      the 51 Medicaid agencies. Survey data were collected and combined with Centers
      for Medicare and Medicaid Services data elements. Where possible, analyses were
      conducted at the state, waiver program, and health plan levels. RESULTS: Findings
      confirmed that most states were contracting to serve a broad range of Medicaid
      enrollees. The array of covered benefits was extensive. Health maintenance
      organization (HMO)-type arrangements accounted for most plans nationally, but 40
      percent of plans were specialty carve-outs. Most states used capitation
      contracts, but a third shared risk with their vendors. A surprising number of
      states (41 percent) reported using governmental entities as vendors. CONCLUSIONS:
      By the year 2000, large numbers of public sector clients were being served by HMO
      type arrangements. Benefit designs under managed care were perhaps more inclusive
      than some advocates had feared. The flexibility of capitation financing may have
      enhanced the ability of health plans to ration care in a clinically informed
      manner. However, large numbers of vulnerable individuals were receiving care
      through fully capitated health plans. This finding suggests the need for
      vigilance by public-sector mental health and substance abuse authorities.
      Authorities should aggressively pursue opportunities to influence Medicaid
      policy.

PMID- 16816286
TI  - Impact of program services on treatment outcomes of patients with comorbid mental
      and substance use disorders.
AB  - OBJECTIVE: This study examined the outcomes of individuals with co-occurring
      disorders who received drug treatment in programs that varied in their
      integration of mental health services. Patients treated in programs that provided
      more on-site mental health services and had staff with specialized training were
      expected to report less substance use and better psychological outcomes at follow
      up. METHODS: Participants with co-occurring disorders were sampled from 11
      residential drug abuse treatment programs for adults in Los Angeles County. In
      depth assessments of 351 patients were conducted at treatment entry and at follow
      up six months later. Surveys conducted with program administrators provided
      information on program characteristics. Latent variable structural equation
      models revealed relationships of patient characteristics and program services
      with drug use and psychological functioning at follow-up. RESULTS: Individuals
      treated in programs that provided specific dual diagnosis services subsequently
      had higher rates of utilizing mental health services over six months and, in
      turn, showed significantly greater improvements in psychological functioning (as
      measured by the Brief Symptom Inventory and the RAND Health Survey 36-item short
      form) at follow-up. More use of psychological services was also associated with
      less heroin use at follow-up. African Americans reported poorer levels of
      psychological functioning than others at both time points and were less likely to
      be treated in programs that provided mental health services. CONCLUSIONS: Study
      findings support continued efforts to provide specialized services for
      individuals with co-occurring disorders within substance abuse treatment programs
      as well as the need to address additional barriers to obtaining these services
      among African Americans.

PMID- 16816287
TI  - Diabetes treatment among VA patients with comorbid serious mental illness.
AB  - OBJECTIVE: Patients with serious mental illnesses, such as schizophrenia, bipolar
      disorder, and other psychoses, may be less likely to receive adequate care for
      chronic medical conditions than patients without serious mental illness. The
      quality and outcomes of diabetes care were compared in an observational study
      among patients with and without serious mental illness. METHODS: National data
      were studied for 36,546 individuals receiving care within the U.S. Department of
      Veterans Affairs (VA) health care system. Widely used diabetes quality-of-care
      measures and intermediate outcomes were compared for patients with diabetes and
      serious mental illness and age-matched patients with diabetes who did not have a
      serious mental illness. Patients' use of health services was also examined.
      RESULTS: During fiscal year 1998, patients with diabetes and serious mental
      illness were as likely as patients with diabetes alone to have their hemoglobin
      A1c, low-density lipoproteins (LDL), and cholesterol measured; both groups had
      comparable A1c, LDL, and cholesterol values. Patients with diabetes and serious
      mental illness had more outpatient visits, both primary care and specialty
      visits, and made more multiclinic visits, including visits to both primary care
      and mental health services on the same day. CONCLUSIONS: In the VA, patients with
      diabetes and serious mental illness appear to receive diabetes care that is
      comparable with the care that other patients with diabetes receive, possibly
      because of increased levels of contact with the health system and the VA's
      integration of medical and mental health services.

PMID- 16816288
TI  - Prevention and management of aggression training and violent incidents on U.K.
      Acute psychiatric wards.
AB  - OBJECTIVE: Reports of violence and injuries to staff and patients in acute
      psychiatric inpatient settings have led to the development and implementation of
      training courses in the Prevention and Management of Violence and Aggression
      (PMVA). The purpose of this study was to explore the relationship between PMVA
      training of acute psychiatric ward nursing staff and officially reported violent
      incident rates. METHODS: A retrospective analysis was conducted of training
      records (312 course attendances) and violent incident rates (684 incidents) over
      two-and-a-half years on 14 acute admission psychiatric wards (5,384 admissions)
      at three inner-city hospitals in the United Kingdom as part of the Tompkins Acute
      Ward Study. RESULTS: A positive association was found between training and rates
      of violent incidents. There was weak evidence that increased rates of aggressive
      incidents prompted course attendance, no evidence that course attendance reduced
      violence, and some evidence that attendance of briefer update courses triggered
      small short-term rises in rates of physical aggression. Course attendance was
      associated with a rise in physical and verbal aggression while staff were away
      from the ward. CONCLUSIONS: The failure to find a drop in incident rates after
      training, coupled with the small increases in incidents detected, raises concerns
      about the training course's efficacy as a preventive strategy. Alternatively, the
      results are consistent with a threshold effect, indicating that once adequate
      numbers of staff have been trained, further training keeps incidents at a low
      rate.

PMID- 16816289
TI  - Clinicians' perspectives on cognitive-behavioral treatment for PTSD among persons
      with severe mental illness.
AB  - OBJECTIVE: As an intermediate step in the development of a cognitive-behavioral
      posttraumatic stress disorder (PTSD) treatment program for persons with severe
      mental illness, a focus group gathered feedback from clinicians and clinical
      supervisors within a public-sector mental health system. METHODS: Five
      qualitative focus group discussions were held with 33 clinicians and clinical
      supervisors within a state-funded community mental health center system. RESULTS:
      Clinicians perceived trauma to be a significant adverse factor in the lives of
      their mental health services consumers, were reluctant to address trauma with
      them, and yet believed that cognitive-behavioral treatments for PTSD may be
      effective and appropriate for them. Clinicians also offered practical suggestions
      to improve the feasibility and acceptability of the proposed cognitive-behavioral
      treatment program. Examples include creating gender-specific treatment groups;
      ensuring that trust and rapport with clients are established before the
      discussion of traumatic experiences; developing careful safety precautions for
      clients, especially for the exposure therapy component; preparing for the
      possibility that some consumers will lack the cognitive ability to understand
      treatment; and collaborating with other care providers to ensure optimal
      integration with other aspects of care and minimize clinic disruptions.
      CONCLUSIONS: These findings provide information relevant to the development and
      implementation of PTSD interventions for patients with severe mental illness
      treated in public-sector settings.

PMID- 16816290
TI  - Elevated cancer incidence among adults with serious mental illness.
AB  - OBJECTIVE: Research is increasingly focusing on the health status of adults with
      serious mental illness. This study examined databases in Vermont to determine the
      incidence of cancer in this population. METHODS: Probabilistic statistical
      methods were used to determine the overlap between the Vermont Cancer Registry
      and Vermont mental health treatment databases. RESULTS: The incidence of cancer
      for adults with mental illness was 1.6 percent, more than twice (2.5 times) that
      of the general population. Among persons with mental illness, elevated risk was
      greatest for men younger than 50 years (6.6 times the risk of a comparable group
      in the general population) and lowest for women aged 50 years and older (1.8
      times the risk of a comparable group). CONCLUSIONS: These findings raise
      important questions about the relationship between serious mental illness and
      cancer. Future research should consider the effect of lifestyle factors, and
      potential effects of first- and second-generation antipsychotics should be
      investigated.

PMID- 16816291
TI  - Predictors of tobacco use among persons with mental illnesses in a statewide
      population.
AB  - OBJECTIVE: This study used statewide administrative data sets to estimate the
      prevalence of tobacco use among persons with mental illnesses who were accessing
      public-sector mental health care in Colorado and to determine the relationships
      between tobacco use and primary diagnosis and alcohol and drug use. METHODS: This
      study utilized the Colorado Client Assessment Record to examine predictors of
      tobacco use among 111,984 persons with mental illnesses who were receiving
      services in the public mental health system. RESULTS: Thirty-nine percent of the
      sample (N=43,508) used tobacco. Multiple logistic regression analysis found that
      schizophrenia, schizoaffective disorder, and bipolar disorder (p<.001 for all),
      and depression or dysthymia (p<.01) were associated with greater tobacco use than
      other diagnoses. Significant differences in tobacco use existed across gender,
      age group, race or ethnicity, and substance use categories. CONCLUSIONS: Findings
      suggest that an administrative database is a low-burden means of identifying
      persons at high risk of tobacco use to inform resource allocation.

PMID- 16816292
TI  - Screening psychiatric emergency department patients with major mental illnesses
      for at-risk drinking.
AB  - OBJECTIVE: This study determined the prevalence of at-risk drinking in a
      psychiatric emergency service and compared the characteristics and functioning of
      at-risk drinkers with schizophrenia or bipolar disorder with those of at-risk
      drinkers with depression or anxiety disorders. METHODS: Adult patients who
      entered the psychiatric emergency service and met study criteria were surveyed.
      RESULTS: A total of 148 participants had schizophrenia or bipolar disorder, and
      242 had depression or anxiety. Twenty-three percent of the group with
      schizophrenia or bipolar disorder and 22 percent of the group with depression or
      anxiety drank more than the recommended limits. The group with schizophrenia or
      bipolar disorder reported experiencing significantly more consequences from
      drinking than the depression or anxiety group. Both groups reported significant
      depression in the prior few days. CONCLUSIONS: This study demonstrated the
      importance of assessing alcohol use and depression among all patients in
      psychiatric emergency services.

PMID- 16816293
TI  - Pathways to care for African Americans with early psychosis.
AB  - Research examining pathways to care among African Americans with recent-onset
      psychosis is limited but suggests that African Americans have more complex and
      less desirable routes into care compared with whites. Delays in treatment of
      psychotic illness contribute to increasing rates of hospitalization, lengths of
      stay, long-term functional disability, and poor outcomes. African Americans may
      be less likely to seek help than whites, which may be due partly to stigma and
      beliefs in the African-American community about causes of mental illness as well
      as to external obstacles, such as involuntary civil commitment. Because African
      Americans are more likely than whites to seek assistance in primary care, the
      general practitioner or family physician has a potentially greater role in the
      identification of psychotic illnesses among African Americans. Further research
      is necessary to evaluate the role of ethnicity in treatment delays among patients
      with recent-onset psychotic illnesses.

PMID- 16816294
TI  - Monitoring of patients given second-generation antipsychotic agents.

PMID- 16816295
TI  - The recovery model and seclusion and restraint.

PMID- 16816296
TI  - Psychosocial functioning of Medicaid recipients with major depression.

PMID- 16816297
TI  - Advancing evidence-based practices through psychiatric consultation.

PMID- 16816298
TI  - Beyond the Kraepelinian dichotomy: acute and transient psychotic disorders and
      the necessity for clinical differentiation.
AB  - The concept of acute and transient psychoses is, together with that of
      schizoaffective disorders, a challenge by the Kraepelinian dichotomy. Although
      these conditions have some similarities to schizophrenia, they differ
      significantly from schizophrenia regarding onset, duration, prognosis, gender and
      premorbid adaptation. They show some similarities with bipolar disorders. They do
      not fit into the dichotomous concept.

PMID- 16816299
TI  - Exposure to obstetric complications and subsequent development of bipolar
      disorder: Systematic review.
AB  - BACKGROUND: Research has suggested an association between obstetric complications
      and bipolar disorder. However, no quantitative evaluation has been made of the
      pooled data from existing studies. AIMS: To systematically review studies
      comparing exposure to obstetric complications in cases of bipolar disorder v. non
      psychiatric controls, and in cases of bipolar disorder v. cases of other mental
      disorders. METHOD: Publications were identified by computer searches of seven
      databases, by hand searches of reference lists and from raw data received from
      researchers. RESULTS: Forty-six studies were identified, of which 22 met the
      inclusion criteria. The pooled odds ratio for exposure to obstetric complications
      and subsequent development of bipolar disorder was 1.01 (95% CI 0.76-1.35)
      compared with healthy controls, 1.13 (95% CI 0.64-1.99) compared with cases of
      unipolar disorder and 0.61 (95% CI 0.39-0.95) compared with those who developed
      schizophrenia. CONCLUSIONS: There is no robust evidence that exposure to
      obstetric complications increases the risk of developing bipolar disorder.
      However, the range of events regarded as obstetric complications and
      methodological inadequacies make definitive conclusions difficult.

PMID- 16816300
TI  - Violence and psychiatric morbidity in the national household population of
      Britain: public health implications.
AB  - BACKGROUND: It is unclear whether psychiatric morbidity contributes to the small
      proportion of the population responsible for a large percentage of antisocial
      behaviour, including violence. AIMS: To measure associations between psychiatric
      morbidity and severity, chronicity and types of victims of violence in the
      national household population of Britain. METHOD: Cross-sectional survey of
      persons in households (n = 8397).Data included self-reported location, victims
      and outcome of violence over the previous 5 years. Diagnoses were determined by
      computer-assisted interviews. RESULTS: Hazardous drinking was associated with
      over half of all incidents involving injury. Antisocial personality disorder
      conveyed an attributable risk of 24% of respondents reporting victim injuries,
      but screening positive for psychosis conveyed an attributable risk of only 1.2%.
      CONCLUSIONS: The burden of care resulting from violence associated with hazardous
      drinking supports population interventions. Despite exceptional risks, half of
      respondents with antisocial personality disorder were not violent, indicating
      limitations in targeted interventions to detain high-risk individuals.

PMID- 16816301
TI  - Prospective 12-month course of bipolar disorder in out-patients with and without
      comorbid anxiety disorders.
AB  - BACKGROUND: The impact of anxiety disorders has not been well delineated in
      prospective studies of bipolar disorder. AIMS: To examine the association between
      anxiety and course of bipolar disorder, as defined by mood episodes, quality of
      life and role functioning. METHOD: A thousand thousand out-patients with bipolar
      disorder were followed prospectively for 1 year. RESULTS: A current comorbid
      anxiety disorder (present in 31.9% of participants) was associated with fewer
      days well, a lower likelihood of timely recovery from depression, risk of earlier
      relapse, lower quality of life and diminished role function over I year of
      prospective study. The negative impact was greater with multiple anxiety
      disorders. CONCLUSIONS: Anxiety disorders, including those present during
      relative euthymia, predicted a poorer bipolar course. The detrimental effects of
      anxiety were not simply a feature of mood state. Treatment studies targeting
      anxiety disorders will help to clarify the nature of the impact of anxiety on
      bipolar course.

PMID- 16816302
TI  - Vascular risk factors and incident late-life depression in a Korean population.
AB  - BACKGROUND: Causal relationships between vascular factors and late-life
      depression are controversial. AIMS: To investigate prospective associations
      between risk factors for vascular disease and incidence of late-life depression.
      METHOD: Of 661 community participants aged 65 years or over, without depression
      at baseline, 521 (79%) were re-evaluated 2 years later. At baseline and follow
      up, a diagnostic interview for depression was carried out and information on
      vascular status, disability and cognitive function was gathered. RESULTS: Pre
      existing heart disease, incident stroke and lower baseline high-density
      lipoprotein cholesterol level were significantly associated with incidence of
      late-life depression, independently of disability and cognitive function.
      CONCLUSIONS: These results provide some support for a vascular aetiology of late
      life depression. However, important risk factors for cerebrovascular disease such
      as hypertension and diabetes were not implicated, and the associations with lipid
      levels might still be explained by affective states earlier in life.

PMID- 16816303
TI  - Premorbid functioning and treatment response in recent-onset schizophrenia.
AB  - BACKGROUND: Investigating the relationship between premorbid functioning and
      treatment response in schizophrenia is relevant to understanding the illness and
      predicting treatment outcomes. AIMS: To examine the relationship between
      premorbid characteristics and treatment response of people with recent-onset
      schizophrenia. METHOD: Data came from a large, double-blind trial of recent-onset
      psychosis treated with a flexible dose of risperidone or haloperidol. Median
      treatment length was 206 days. Premorbid functioning was categorised using the
      Cannon-Spoor Premorbid Adjustment Scale. RESULTS: There were significant
      differences between the premorbid groups on change on the Positive and Negative
      Syndrome Scale, Clinical Global Impression severity and cognitive functioning and
      Extrapyramidal Symptoms Rating Scale. Patients in the ;stable-good' premorbid
      group (n = 251) improved more than those in the'stable-poor' (n = 198) and
      'declining' (n = 81) groups. The ;stable-good' group received the lowest doses of
      antipsychotic and had the least extrapyramidal symptoms. Patients in the
      'declining' group had the highest dosages and the most extrapyramidal symptoms.
      CONCLUSIONS: In first-episode psychosis good premorbid functioning is associated
      with better response to treatment and fewer extrapyramidal symptoms.

PMID- 16816304
TI  - Outcomes of an effectiveness trial of cognitive-behavioural intervention by
      mental health nurses in schizophrenia.
AB  - BACKGROUND: Little is known about the medium-term durability of cognitive
      behavioural therapy (CBT) in a community sample of people with schizophrenia.
      AIMS: To investigate whether brief CBT produces clinically important outcomes in
      relation to recovery, symptom burden and readmission to hospital in people with
      schizophrenia at 1-year follow-up. METHOD: Participants (336 of 422 randomised at
      baseline) were followed up at a mean of 388 days (s.d. = 53) by raters masked to
      treatment allocation (CBT or usual care). RESULTS: At 1-year follow-up,
      participants who received CBT had significantly more insight (P = 0.021) and
      significantly fewer negative symptoms (P = 0.002). Brief therapy protected
      against depression with improving insight and against relapse; significantly
      reduced time spent in hospital for those who did relapse and delayed time to
      admission. It did not improve psychotic symptoms or occupational recovery, nor
      have a lasting effect on overall symptoms or depression at follow-up.
      CONCLUSIONS: Mental health nurses should be trained in brief CBT for
      schizophrenia to supplement case management, family interventions and expert
      therapy for treatment resistance.

PMID- 16816305
TI  - Effects of a mutual support group for families of Chinese people with
      schizophrenia: 18-month follow-up.
AB  - BACKGROUND: Family intervention in schizophrenia can reduce patient relapse and
      improve medication adherence, but few studies on this have involved a Chinese
      population. AIMS: To examine the effects of a mutual support group for Chinese
      families of people with schizophrenia, compared with psychoeducation and standard
      care. METHOD: Randomised controlled trial in Hong Kong with 96 families of out
      patients with schizophrenia, of whom 32 received mutual support, 33
      psychoeducation and 31 standard care. The psychoeducation group included patients
      in all the sessions, the mutual support group did not. Intervention was provided
      over 6 months, and patient- and family-related psychosocial outcomes were
      compared over an 18-month follow-up. RESULTS: Mutual support consistently
      produced greater improvement in patient and family functioning and caregiver
      burden over the intervention and follow-up periods, compared with the other two
      conditions. The number of readmissions did not decrease significantly, but their
      duration did. CONCLUSIONS: Mutual support for families of Chinese people with
      schizophrenia can substantially benefit family and patient functioning and
      caregiver burden.

PMID- 16816306
TI  - Cost-effectiveness of referral for generic care or problem-solving treatment from
      community mental health nurses, compared with usual general practitioner care for
      common mental disorders: Randomised controlled trial.
AB  - BACKGROUND: UK general practitioners (GPs) refer patients with common mental
      disorders to community mental health nurses. AIMS: To determine the effectiveness
      and cost-effectiveness of this practice. METHOD: Randomised trial with three
      arms: usual GP care, generic mental health nurse care, and care from nurses
      trained in problem-solving treatment; 98 GPs in 62 practices referred 247 adult
      patients with new episodes of anxiety, depression and life difficulties, to 37
      nurses. RESULTS: There were 212 (86%) and 190 (77%) patients followed up at 8 and
      26 weeks respectively. No significant differences between groups were found in
      effectiveness at either point. Mean differences in Clinical Interview Schedule -
      Revised scores at 26 weeks compared with GP care were -1.4 (95% CI -5.5 to 2.8)
      for generic nurse care, and 1.1 (-2.9 to 5.1) for nurse problem-solving.
      Satisfaction was significantly higher in both nurse-treated groups. Mean extra
      costs per patient were 283 pound (95% CI154-411) for generic nurse care, and 315
      pound (183-481) for nurse problem-solving treatment. CONCLUSIONS: GPs should not
      refer unselected patients with common mental disorders to specialist nurses.
      Problem-solving should be reserved for patients who have not responded to initial
      GP care.

PMID- 16816307
TI  - Comparison of brief dynamic and cognitive-behavioural therapies in avoidant
      personality disorder.
AB  - BACKGROUND: There is a paucity of controlled trials examining the effectiveness
      of individual psychotherapy in personality disorders, especially in patients with
      cluster C disorders. AIMS: To compare the effectiveness of brief dynamic therapy
      and cognitive-behavioural therapy as out-patient treatment for people with
      avoidant personality disorder. METHOD: Patients who met the criteria for avoidant
      personality disorder (n=62) were randomly assigned to 20 weekly sessions of
      either brief dynamic therapy (n = 23) or cognitive-behavioural therapy (n=21), or
      they were assigned to the waiting-list control group (n = 18). After the waiting
      period, patients in the control group were randomly assigned to one of the two
      therapies. RESULTS: Patients who received cognitive-behavioural therapy showed
      significantly more improvements on a number of measures in comparison with those
      who had brief dynamic psychotherapy or were in the waiting-list control group.
      Results were maintained at follow-up. CONCLUSIONS: Cognitive-behavioural therapy
      is more effective than waiting-list control and brief dynamic therapy. Brief
      dynamic therapy was no better than the waiting-list control condition.

PMID- 16816308
TI  - Generalisability of the individual placement and support model of supported
      employment: results of a Canadian randomised controlled trial.
AB  - BACKGROUND: Studies conducted in the USA have found the individual placement and
      support model of supported employment to be more effective than traditional
      vocational rehabilitation at helping people with severe mental illness to find
      and maintain competitive employment. AIMS: To determine the effectiveness of the
      individual placement and support (supported employment) model in a Canadian
      setting. METHOD: A total of 150 adults with severe mental illness, who were not
      currently employed and who desired competitive employment, were randomly assigned
      to receive either supported employment (n = 75) or traditional vocational
      services (n = 75). RESULTS: Over the 12 months of followup, 47% of clients in the
      supported employment group obtained at least some competitive employment, v. 18%
      of the control group (P < 0.001). They averaged 126 h of competitive work, v. 72
      in the control group (P < 0.001). CONCLUSIONS: Supported employment proved more
      effective than traditional vocational services in a setting significantly
      different from settings in the USA, and may therefore be generalised to settings
      in other countries.

PMID- 16816310
TI  - Duration of untreated symptoms in common mental disorders: association with
      outcomes: International study.
AB  - Studies have assessed the association between a longer duration of untreated
      symptoms and outcome for psychoses in specialist care. We investigated the effect
      of longer duration on the outcome of common psychiatric disorders in primary
      care, where most patients are treated. Patients presenting to primary care for
      new episodes in 10 countries were recruited into a prospective cohort study.
      Information on duration of untreated symptoms and psychosocial status was
      collected for 351 individuals using standardised instruments and this was
      repeated 1 year later. At 1-year follow-up, longer duration was associated with
      worse psychiatric outcome even after controlling for potential confounders.

PMID- 16816309
TI  - Experiences and expectations of refugee doctors: Qualitative study.
AB  - BACKGROUND: Refugee doctors constitute a potentially valuable resource for
      reducing the recruitment crisis in psychiatry. However, various hurdles make
      their route into the National Health Service (NHS) difficult. AIMS: To explore
      the perceptions and experiences of refugee doctors trying to practise psychiatry
      in the UK. METHOD: Thirty-one refugee doctors participated in qualitative
      interviews designed to elicit their experiences in trying to practise as doctors
      in the UK. Twenty were re-interviewed about 6 months later. RESULTS: Doctors
      identified a range of practical problems that made it difficult for them to take
      the required steps towards practising in the UK. These included lack of
      appropriate information, lack of a clear route through the system and feelings of
      isolation. The English language examination was seen as a particular bottleneck,
      as were finding clinical attachments. The psychological impact of the experience
      was profound. CONCLUSIONS: These findings have important implications for how
      refugee doctors are introduced to the practice of psychiatry in the NHS.

PMID- 16816311
TI  - Magnetic resonance imaging abnormalities in young euthymic patients with bipolar
      affective disorder.
AB  - Temporal lobe and limbic structures may be abnormal in bipolar disorder. T2
      weighted magnetic resonance imaging (MRI) scans frequently show deep white matter
      lesions. MRI was performed on 50 young (19-39 years) euthymic patients with
      bipolar disorder and 26 controls. Mean temporal lobe volumes were reduced in
      patients (right, 9.42 cm3; left, 6.33 cm3) but this could not but this could not
      be ascribed to a specific structure. Deep white matter lesions were present in 5
      patients but no controls raising questions of their aetiological significance.

PMID- 16816312
TI  - Ethical framework in clinical psychiatry.

PMID- 16816313
TI  - Ethical framework in clinical psychiatry.

PMID- 16816314
TI  - Ethical framework in clinical psychiatry.

PMID- 16816315
TI  - Job satisfaction of mental health social workers.

PMID- 16816316
TI  - Ethical framework in clinical psychiatry.

PMID- 16816317
TI  - Psychological factors in bipolar disorder.

PMID- 16816318
TI  - What is pathological lying?

PMID- 16816319
TI  - A typological analysis of behavioral profiles of sexually abused children.
AB  - A cluster analysis is used to explore differential outcomes in 123 French
      Canadian children reporting sexual abuse contrasted with 123 control children.
      Mothers' reports of behavioral problems on the Child Behavior Checklist, abuse
      related variables, personal factors, and family characteristics are used as
      potential variables discriminating clusters. Results reveal four clusters: (a)
      anxiety constellation group refers to children displaying behavior problems on a
      subset of scales, (b) the severe distress group refers to children showing a
      broader array of behavior problems, (c) victims of less severe sexual abuse (SA)
      group consists of children disclosing mostly extrafamilial SA, and (d) resilient
      children refers to children who, while disclosing severe abuse, rely less on
      avoidance coping. Findings underscore the need to go beyond abuse-related
      variables to orient treatment for children disclosing sexual abuse and for
      tailoring interventions to distinct subgroups.

PMID- 16816320
TI  - Creating and field-testing child maltreatment definitions: improving the
      reliability of substantiation determinations.
AB  - The decision to substantiate a case of maltreatment is pivotal to myriad
      stakeholders; however, the reliability (and therefore, accuracy) of
      substantiation determinations is suspect. The authors tested if (a) they could
      develop more reliable substantiation definitions and processes and (b) case
      workers would be comfortable with and accepting of a new approach. Determinations
      from five field sites were compared with those of master reviewers (made while
      listening to the field sites' case presentations). Agreement, sensitivity,
      specificity, positive predictive values, and negative predictive values were high
      overall (.87, .96, .97, .89, and .97, respectively) and for each form of
      maltreatment. Agreement was substantially improved. The definitions and the
      determination process were well liked by case workers and other stakeholders.
      Clearly, implementing standardized definitions in a typical child protective
      environment would pose myriad political challenges. However, our results suggest
      achieving reliable substantiation determinations may be a feasible goal.

PMID- 16816321
TI  - Childhood sexual abuse among Black women and White women from two-parent
      families.
AB  - Differences in childhood sexual abuse (CSA) between Black women and White women
      are explored in a community sample of 290 women raised in two-parent families.A
      self-administered questionnaire and a face-to-face interview assessed CSA
      characteristics, aftermath, and prevalence as well as family structure and other
      childhood variables. Siblings served as collateral informants for the occurrence
      of CSA. Overall, comparisons of the nature, severity, and aftermath of CSA showed
      similarities by race; some differences, for example, in age of onset, are
      potentially relevant for the planning of prevention programs. Logistic regression
      models examined effects of childhood variables on CSA prevalence. Initial
      analyses showed a higher CSA prevalence among Black women (34.1% [45] of Black
      women vs. 22.8% [36] of White women) that was attenuated when family structure
      (e.g., living with two biological parents throughout childhood or not) and social
      class were considered. Of interest, differences in family structure remained
      important even among these two-parent families. Understanding the dynamics of
      abuse by race and family structure will facilitate the design of more targeted
      CSA prevention programs.

PMID- 16816322
TI  - Child Protective Services referrals in cases of sudden infant death: a 10-year,
      population-based analysis in San Diego County, California.
AB  - The potential diagnostic significance of prior family referral to Child
      Protective Services (CPS) in cases of sudden infant death is unknown. Therefore,
      the authors retrospectively searched for CPS data for the 5-year referral history
      on all 533 families whose infants died suddenly from Sudden Infant Death Syndrome
      (SIDS), other natural diseases, accidents, or inflicted injuries and underwent
      postmortem examination by the medical examiner during a 10-year period. No family
      had more than one infant death. At least 27% of the families in each group had at
      least one CPS referral. The data suggest that a family's referral to CPS prior to
      their sudden death of their infant does not increase the likelihood that it was
      caused by inflicted injuries, and prior referral should not preclude a diagnosis
      of SIDS. The authors recommend future prospective studies that include refined
      exposure histories and that are large enough to have sufficient statistical power
      to compare family CPS referrals and outcomes in groups of infants who died
      suddenly with a matched group of living infants.

PMID- 16816323
TI  - Reporting participants in research studies to Child Protective Services: limited
      risk to attrition.
AB  - This study examines the impact of Child Protective Services (CPS) reports made by
      research study staff on participant retention and discusses human subjects
      protocols that may minimize either the need to make such reports or the negative
      impact of reporting on participants and on participant retention. Among 1, 354
      primary caregiver-child pairs in the Longitudinal Studies of Child Abuse and
      Neglect (LONGSCAN) studies, a total of 15 were reported to CPS by study staff.
      Within this group, rates of study-generated reports and study participation
      subsequent to having been reported by researchers were examined. There was an
      overall retention rate of 93% across a minimum of three interview waves in this
      sample. Reporting research participants to CPS may have little impact on
      attrition.

PMID- 16816324
TI  - Understanding the ecology of child maltreatment: a review of the literature and
      directions for future research.
AB  - Studies examining neighborhood characteristics in relation to social problems,
      including child maltreatment, have proliferated in the past 25 years. This
      article reviews the current state of knowledge of ecological studies of child
      maltreatment. Taken as a whole, these 18 studies document a stable ecological
      relationship among neighborhood impoverishment, housing stress, and rates of
      child maltreatment, as well as some evidence that unemployment, child care
      burden, and alcohol availability may contribute to child abuse and neglect. The
      authors include a discussion of methodological difficulties in conducting
      research at the neighborhood level and present a set of recommendations for
      future research that emphasizes movement from a simple examination of
      neighborhood-level characteristics toward a theoretically driven explication of
      processes and mechanisms supported by appropriate multilevel modeling techniques.
      The final goal of such efforts would be to enable practitioners to develop
      evidence-based neighborhood interventions that would prevent and reduce child
      abuse and neglect.

PMID- 16816325
TI  - The potential for child neglect: the case of adolescent mothers and their
      children.
AB  - The present study examines the role of neglect potential in adolescent mother
      child dyads, both in terms of antecedents and its consequences for children's
      development. Participants were 100 adolescent mother-child dyads who were part of
      a larger, longitudinal study. Data were collected from the third trimester of
      pregnancy until the children's 10th year. Histories of maternal neglect and the
      quality of mother-child interactions during early childhood were found to predict
      neglect potential during middle childhood. Mothers with high neglect potential
      had children who exhibited more externalizing problems and fewer adaptive
      behaviors, with neglect potential mediating the effects of both early abuse
      potential and the quality of parenting on children's later externalizing
      behaviors. Results suggest that neglect potential may be a mechanism through
      which early potential for child abuse and insensitive maternal interactions
      affect later externalizing problems in children of adolescent mothers.

PMID- 16816326
TI  - The age-related paraoxonase 1 response is altered by long-term caloric
      restriction in male and female rats.
AB  - Caloric restriction (CR) has been shown to attenuate age-related oxidative damage
      and to improve major atherosclerotic risk factors. Paraoxonase 1 (PON1), an
      enzyme specifically associated with HDL containing apolipoproteins A-I and J, has
      been reported to prevent the proatherosclerotic effects of oxidized LDL. The aim
      of this study was to evaluate whether modulation of PON1 activity is part of the
      underlying CR mechanisms that attenuate the age-associated negative effects.
      Experimental groups were 1 year old rats of both genders subjected to 40% CR for
      1 year and two ad libitum-fed groups, also including rats of both genders,
      euthanized at 6 months or 2 years. Aging impaired the serum lipid profile and
      increased lipid peroxidation, PON1 activities, and the content of both PON1 and
      apolipoprotein J in HDL, which suggests an HDL subfraction redistribution to
      protect LDL more effectively from oxidation. The CR-associated improved lipid
      profile and the decreased lipid peroxide levels would lead to the decreased
      arylesterase activity seen in old CR animals, suggesting that PON1 modulation is
      not an integral part of the main antioxidant mechanisms of CR but rather that CR
      would determine a more youthful and less oxidative situation in which the
      protection of LDL would be less necessary.

PMID- 16816327
TI  - Conjugated linoleic acid and hepatic lipogenesis in mouse: role of the
      mitochondrial citrate carrier.
AB  - Conjugated linoleic acid (CLA) is able to reduce adiposity by affecting lipid
      metabolism. In particular, CLA administration to mice reduces body fat mass with
      a concomitant lipid accumulation in the liver. We investigated the effects of CLA
      on the activity of the mitochondrial citrate carrier (CIC), which is implicated
      in hepatic lipogenesis. The transport activity of the CIC, measured both in
      intact mitochondria and in the proteoliposomes, progressively increased with the
      duration of CLA feeding. An increase in the CIC activity of approximately 1.7
      fold was found in 16 week CLA-treated mice with respect to control animals. A
      kinetic analysis showed a 1.6-fold increase in the V(max) of citrate transport
      but no change in the K(m) value. Western blot experiments revealed an increase of
      approximately 1.7-fold in the expression of CIC after CLA treatment. A strict
      correlation between the increase in CIC activity and the stimulation of the
      cytosolic lipogenic enzymes was also found. These data indicate that the CIC may
      play a role in the onset of hepatic steatosis in CLA-fed mice by supplying the
      carbon source for de novo fatty acid synthesis.

PMID- 16816328
TI  - Large-scale gene expression studies of the endometrium: what have we learnt?
AB  - The endometrium is a dynamic tissue that undergoes coordinated changes under the
      influence of steroid hormones. This results in proliferation and differentiation
      culminating in a receptive state, followed by menstruation and endometrial
      repair. These functions involve complex interactions between the epithelium,
      stroma and leucocytes in the endometrium. Understanding the underlying causes of
      endometrial disorders, such as infertility, endometriosis and heavy menstrual
      bleeding, therefore represents a considerable challenge. Recently developed
      techniques, such as differential display and DNA microarrays permit the abundance
      of thousands of mRNA transcripts within cells or tissues to be measured
      simultaneously. This provides a new approach to understanding the complex
      interactions that underlie both healthy and disease states. Responses of the
      endometrium to hormones or drugs can be studied and the response of the system as
      an integrated whole can be assessed. Comparisons of endometrium from healthy
      women and those with endometrial dysfunction have advanced our understanding of
      key areas of endometrial physiology, including infertility, receptivity,
      endometriosis and cancer. Using this approach, novel genes controlling specific
      endometrial functions like receptivity have been identified for functional
      testing. This paper will review the impact of these techniques for transcript
      profiling on our understanding of selected areas of endometrial biology and
      discuss the potential applications in future.

PMID- 16816329
TI  - Microarray technology offers a novel tool for the diagnosis and identification of
      therapeutic targets for male infertility.
AB  - Male infertility is now a major reproductive health problem because of an
      increasing number of environmental pollutants and chemicals, which eventually
      result in gene mutations. Genetic alterations caused by environmental factors
      account for a significant percentage of male infertility. Microarray technology
      is a powerful tool capable of measuring simultaneously the expression of
      thousands of genes expressed in a single sample. Eventually, advances in genetic
      technology will allow for the diagnosis of patients with male infertility due to
      congenital reasons or environmental factors. Since its introduction in 1994,
      microarray technology has made significant advances in the identification and
      characterization of novel or known genes possibly correlated with male
      infertility in mice, as well as in humans. This provides a rational basis for the
      application of microarray to establishing molecular signatures for the diagnosis
      and gene therapy targets of male infertility. In this review, the differential
      gene expression patterns characterized by microarray in germ and somatic cells at
      different steps of development or in response to stimuli, as well as a number of
      novel or known genes identified to be associated with male infertility in mice
      and humans, are addressed. Moreover, issues pertaining to measurement
      reproducibility are highlighted for the application of microarray data to male
      infertility.

PMID- 16816330
TI  - Cytoplasmic polyadenylation controls cdc25B mRNA translation in rat oocytes
      resuming meiosis.
AB  - Resumption of meiosis in oocytes represents the entry into M-phase of the cell
      cycle and is regulated by the maturation-promoting factor (MPF). Activation of
      MPF is catalyzed by the dual specificity phosphatase, cdc25. In mammals, cdc25 is
      represented by a multigene family consisting of three isoforms: A, B and C. A
      recent report that female mice lacking cdc25B exhibit impaired fertility suggests
      a role for this isoform in regulating the G2- to M-transition in mammalian
      oocytes. Supporting the above-mentioned observation, we demonstrate herein that
      microinjection of neutralizing antibodies against cdc25B interfered with the
      ability of rat oocytes to undergo germinal vesicle breakdown (GVB). We also show
      accumulation of cdc25B in GVB oocytes and a transient reduction in its amount at
      metaphase I of meiosis. The accumulation of cdc25B was associated with its mRNA
      cytoplasmatic polyadenylation and was prevented by the protein synthesis
      inhibitor cyclohexamide as well as by the polyadenylation inhibitor cordycepin.
      Immunofluorescence staining revealed translocation of cdc25B to the metaphase II
      spindle apparatus. Taken together, our findings provide evidence that cdc25B is
      involved in resumption of meiosis in rat oocytes. We further demonstrate for the
      first time, a periodic accumulation of cdc25B throughout meiosis that is
      translationally regulated and involves cdc25B mRNA polyadenylation.

PMID- 16816331
TI  - An active protein kinase A (PKA) is involved in meiotic arrest of rat growing
      oocytes.
AB  - Reinitiation of meiosis in meiotically competent, fully grown mammalian oocytes
      is governed by a fall in intraoocyte cAMP concentrations and the subsequent
      inactivation of protein kinase A (PKA). A similar reduction in intraoocyte cAMP
      concentrations in growing, meiotically incompetent rat oocytes not leading to
      resumption of meiosis, questions the involvement of PKA in the regulation of
      meiosis at this early stage of oocyte development. We examined the possibility of
      whether PKA activity maintains growing oocytes in meiotic arrest and further
      explored the mode of activation of PKA under conditions of relatively low cAMP
      concentrations. Our experiment demonstrated that inactivation of PKA stimulates
      growing rat oocytes to resume meiosis, and elevates the activity of their
      maturation-promoting factor (MPF). We also found that the expressions of type I
      and type II regulatory subunits (RI and RII) of PKA are higher in growing and
      fully grown oocytes, respectively. In addition, we revealed that the common 1:1
      ratio between the regulatory (R) and catalytic (C) subunits of PKA is apparently
      not abrogated and, in accordance PKA activity in growing oocyte-cell extract is
      fully dependent on cAMP. Finally, we identified in growing oocytes, the A kinase
      anchoring protein (AKAP) 140, which was previously depicted in fully grown
      oocytes. We conclude that an active PKA prevents growing oocytes from resuming
      meiosis. Our findings further suggest that relatively high abundance of the PKAI
      isoform and/or its subcellular compartmentalization, through interaction with
      AKAP140, could possibly account for the high basal PKA activity at relatively low
      intraoocyte cAMP concentrations.

PMID- 16816332
TI  - The absence of a Ca(2+) signal during mouse egg activation can affect
      parthenogenetic preimplantation development, gene expression patterns, and
      blastocyst quality.
AB  - A series of Ca(2+) oscillations during mammalian fertilization is necessary and
      sufficient to stimulate meiotic resumption and pronuclear formation. It is not
      known how effectively development continues in the absence of the initial Ca(2+)
      signal. We have triggered parthenogenetic egg activation with cycloheximide that
      causes no Ca(2+) increase, with ethanol that causes a single large Ca(2+)
      increase, or with Sr(2+) that causes Ca(2+) oscillations. Eggs were co-treated
      with cytochalasin D to make them diploid and they formed pronuclei and two-cell
      embryos at high rates with each activation treatment. However, far fewer of the
      embryos that were activated by cycloheximide reached the blastocyst stagecompared
      tothose activated by Sr(2+) orethanol. Any cycloheximide-activated embryos that
      reached the blastocyst stage had a smaller inner cell mass number and a greater
      rate of apoptosis than Sr(2+)-activated embryos. The poor development of
      cycloheximide-activated embryos was due to the lack of Ca(2+) increase because
      they developed to blastocyst stages at high rates when co-treated with Sr(2+) or
      ethanol. Embryos activated by either Sr(2+) or cycloheximide showed similar signs
      of initial embryonic genome activation (EGA) when measured using a reporter gene.
      However, microarray analysis of gene expression at the eight-cell stage showed
      that activation by Sr(2+) leads to a distinct pattern of gene expression from
      that seen with embryos activated by cycloheximide. These data suggest that
      activation of mouse eggs in the absence of a Ca(2+) signal does not affect
      initial parthenogenetic events, but can influence later gene expression and
      development.

PMID- 16816333
TI  - Generation of embryonic stem cell lines from mouse blastocysts developed in vivo
      and in vitro: relation to Oct-4 expression.
AB  - Embryonic stem (ES) cells are the source of all embryonic germ layer tissues. Oct
      4 is essential for their pluripotency. Since in vitro culture may influence Oct-4
      expression, we investigated to what extent blastocysts cultured in vitro from the
      zygote stage are capable of expressing Oct-4 and generating ES cell lines. We
      compared in vivo with in vitro derived blastocysts from B6D2 mice with regard to
      Oct-4 expression in inner cell mass (ICM) outgrowths and blastocysts. ES cells
      were characterized by immunostaining for alkaline phosphatase (ALP), stage
      specific embryonic antigen-1 (SSEA-1) and Oct-4. Embryoid bodies were made to
      evaluate the ES cells' differentiation potential. ICM outgrowths were
      immunostained for Oct-4 after 6 days in culture. A quantitative real-time PCR
      assay was performed on individual blastocysts. Of the in vitro derived
      blastocysts, 17% gave rise to ES cells vs 38% of the in vivo blastocysts. Six-day
      old outgrowths from in vivo developed blastocysts expressed Oct-4 in 55% of the
      cases vs 31% of the in vitro derived blastocysts. The amount of Oct-4 mRNA was
      significantly higher for freshly collected in vivo blastocysts compared to in
      vitro cultured blastocysts. In vitro cultured mouse blastocysts retain the
      capacity to express Oct-4 and to generate ES cells, be it to a lower level than
      in vivo blastocysts.

PMID- 16816334
TI  - Gene expression profiles of Spo11-/- mouse testes with spermatocytes arrested in
      meiotic prophase I.
AB  - Spo11, a meiosis-specific protein, introduces double-strand breaks on chromosomal
      DNA and initiates meiotic recombination in a wide variety of organisms. Mouse
      null Spo11 spermatocytes fail to synapse chromosomes and progress beyond the
      zygotene stage of meiosis. We analyzed gene expression profiles in Spo11(-/ 
      )adult and juvenile wild-type testis to describe genes expressed before and after
      the meiotic arrest resulting from the knocking out of Spo11. These genes were
      characterized using the Gene Ontology data base. To focus on genes involved in
      meiosis, we performed comparative gene expression analysis of Spo11(-/ -)and wild
      type testes from 15-day mice, when spermatocytes have just entered pachytene. We
      found that the knockout of Spo11 causes dramatic changes in the level of
      expression of genes that participate in meiotic recombination (Hop2, Brca2, Mnd1,
      FancG) and in the meiotic checkpoint (cyclin B2, Cks2), but does not affect genes
      encoding protein components of the synaptonemal complex. Finally, we discovered
      unknown genes that are affected by the disruption of the Spo11 gene and therefore
      may be specifically involved in meiosis and spermatogenesis.

PMID- 16816335
TI  - Duplicated insertion mutation in the microtubule-associated protein Spag5
      (astrin/MAP126) and defective proliferation of immature Sertoli cells in rat
      hypogonadic (hgn/hgn) testes.
AB  - Male rats with hypogonadism (hgn/hgn) experience sterility from testicular
      dysplasia, which is controlled by a single recessive gene, hgn. The postnatal
      growth of the seminiferous tubules was severely affected. In this study, we
      localized the hgn locus to a 320 kb region on rat chromosome 10 and detected the
      insertion of a 25 bp duplication into the sixth exon of the sperm-associated
      antigen 5 (Spag5/astrin/MAP126) gene, which codes for a microtubule-associated
      protein. This mutation results in a truncated Spag5 protein lacking the primary
      spindle-targeting domain at the C terminus. Immunological staining with
      antibodies to markers for Sertoli and germ cells during the early postnatal
      period indicated that the abnormal mitosis with dispersed chromosomes in hgn/hgn
      testes occurs in proliferating Sertoli cells. Therefore, apoptotic Sertoli cell
      death would result from the disorganization of the spindle apparatus caused by
      defective Spag5. These findings suggested that the Spag5 is essential for testis
      development in rats and that the hgn/hgn rat is a unique animal model for
      studying the function of Spag5.

PMID- 16816336
TI  - Quantification of healthy follicles in the neonatal and adult mouse ovary:
      evidence for maintenance of primordial follicle supply.
AB  - Proliferation and partial meiotic maturation of germ cells in fetal ovaries is
      believed to establish a finite, non-renewable pool of primordial follicles at
      birth. The supply of primordial follicles in postnatal life should be depleted
      during folliculogenesis, either undergoing atresia or surviving to ovulation.
      Recent studies of mouse ovaries propose that intra- and extraovarian germline
      stem cells replenish oocytes and form new primordial follicles. We quantified all
      healthy follicles in C57BL/6 mouse ovaries from day 1 to 200 using unbiased
      stereological methods, immunolabelling of oocyte meiosis (germ cell nuclear
      antigen (GCNA)) and ovarian cell proliferation (proliferating cell nuclear
      antigen (PCNA)) and electronmicroscopy. Day 1 ovaries contained 7924+/-1564
      (s.e.m.) oocytes or primordial follicles, declining on day 7 to 1987+/-203, with
      200-800 oocytes ejected from individual ovaries on that day and day 12. Discarded
      oocytes and those subjacent to the surface epithelium were GCNA-positive
      indicating their incomplete meiotic maturation. From day 7 to 100 mean numbers of
      primordial follicles per ovary were not significantly depleted but declined at
      200 days to 254+/-71. Mean numbers of all healthy follicles per ovary were not
      significantly different from day 7 to 100 (range 2332+/-349-3007+/-322).
      Primordial follicle oocytes were PCNA-negative. Occasional unidentified cells
      were PCNA-positive with mitotic figures observed in the cortex of day 1 and 12
      ovaries. Although we found no evidence for ovarian germline stem cells, our data
      support the hypothesis of postnatal follicle renewal in postnatal and adult
      ovaries of C57BL/6 mice.

PMID- 16816337
TI  - Temporal relationship between proliferating and apoptotic hormone-producing and
      endothelial cells in the equine corpus luteum.
AB  - The temporal relationship between endothelial cell death, vascular regression and
      the death of hormone-producing cells in the mare has not been established. To
      determine the dynamics of cell proliferation and death throughout the luteal
      phase, corpora lutea were studied at the early, mid- and late luteal phase, and
      after treatment with cloprostenol in the mid-luteal phase to induce premature
      luteolysis. Changes in cell proliferation and apoptosis were investigated
      utilising specific markers (phosphorylated histone-3 and activated caspase-3
      respectively). Histone-3 positive cells were most abundant during the early
      luteal phase, and were mainly present in endothelial cells. Histone-3 activity
      significantly increased in hormone-producing cells 36 h after cloprostenol
      treatment. Frequency of activated caspase-3 staining peaked on day 14, and was
      induced by 36 h after cloprostenol administration in mid-luteal phase. However,
      cell death occurred simultaneously in the endothelial and hormone-producing
      cells. These results show that a subset of hormone-producing cells enter the
      early stages of cell division around luteolysis, while the majority of cells are
      undergoing cell death. Natural and induced functional and structural luteal
      regression in the mare can be at least partially attributed to simultaneous
      apoptosis of endothelial and hormone-producing cells. However, there is no
      evidence that endothelial cell death is the trigger for naturally occurring
      luteolysis.

PMID- 16816338
TI  - Formation of ovarian follicular fluid may be due to the osmotic potential of
      large glycosaminoglycans and proteoglycans.
AB  - During mammalian follicle development, a fluid-filled antrum develops in the
      avascular centre of the follicle. We investigated the hypothesis that follicular
      fluid contains osmotically-active molecules, sufficiently large so as to not
      freely escape the follicular fluid. Such molecules could generate an osmotic
      differential and thus recruit fluid from the surrounding vascularised stroma into
      the antrum. Follicular fluid was collected from bovine follicles classified
      histologically as healthy (n = 4 pools) or atretic (n = 4 pools). Dialysis of the
      follicular fluid at 300 kDa or 500 kDa resulted in a reduction in colloid osmotic
      pressure of 35% and 60%, respectively, in fluid from healthy follicles and 29%
      and 80% from atretic follicles. Digestion of follicular fluid with Streptomyces
      hyaluronidase, chondroitinase ABC or DNase 1 followed by dialysis resulted in
      reductions in osmotic pressure of 43%, 53% and 43% respectively for fluids from
      healthy follicles and 34%, 20% and 31% for atretic follicles. Digestion with
      collagenase I, proteinase K, heparanase 1 or keratanase had no significant effect
      on the osmotic pressure of follicular fluid of healthy follicles. Ion exchange
      and size exclusion, Western blotting and ELISA identified the proteoglycans
      versican and inter-alpha trypsin inhibitor and the glycosaminoglycan hyaluronan
      in follicular fluid. We conclude that these molecules or aggregates of them are
      of sufficient size to contribute to the osmotic potential of follicular fluid and
      thus recruit fluid into the follicular antrum. DNA may also contribute but it is
      probably not a component that is regulated for this role.

PMID- 16816339
TI  - Luteinization of porcine preovulatory follicles leads to systematic changes in
      follicular gene expression.
AB  - The LH surge initiates the luteinization of preovulatory follicles and causes
      hormonal and structural changes that ultimately lead to ovulation and the
      formation of corpora lutea. The objective of the study was to examine gene
      expression in ovarian follicles (n = 11) collected from pigs (Sus scrofa
      domestica) approaching estrus (estrogenic preovulatory follicle; n = 6 follicles
      from two sows) and in ovarian follicles collected from pigs on the second day of
      estrus (preovulatory follicles that were luteinized but had not ovulated; n = 5
      follicles from two sows). The follicular status within each follicle was
      confirmed by follicular fluid analyses of estradiol and progesterone ratios.
      Microarrays were made from expressed sequence tags that were isolated from cDNA
      libraries of porcine ovary. Gene expression was measured by hybridization of
      fluorescently labeled cDNA (preovulatory estrogenic or -luteinized) to the
      microarray. Microarray analyses detected 107 and 43 genes whose expression was
      decreased or increased (respectively) during the transition from preovulatory
      estrogenic to -luteinized (P<0.01). Cells within preovulatory estrogenic
      follicles had a gene-expression profile of proliferative and metabolically active
      cells that were responding to oxidative stress. Cells within preovulatory
      luteinized follicles had a gene-expression profile of nonproliferative and
      migratory cells with angiogenic properties. Approximately, 40% of the discovered
      genes had unknown function.

PMID- 16816340
TI  - Seminal plasma regulates ovarian progesterone production, leukocyte recruitment
      and follicular cell responses in the pig.
AB  - Seminal plasma (SP) acts to influence the uterine endometrium after mating,
      activating synthesis of embryotrophic cytokines and inflammatory changes that
      condition the tract for embryo implantation and establishing pregnancy. The
      objective of this study was to investigate in pigs whether the ovary might also
      be responsive to SP exposure. Prepubertal gilts were synchronised with exogenous
      gonadotrophins and received transcervical treatment with pooled boar SP or PBS;
      then the ovarian tissue was recovered at 34 h (preovulation) and on days 5 and 9
      after treatment. The ovarian response was assessed by measuring ovulation rate,
      number and size of corpora lutea, ovarian leukocyte populations, progesterone
      production in vivo, as well as responses of retrieved granulosa cells cultured in
      vitro. In SP-treated gilts, leukocyte recruitment into the ovarian tissues was
      increased fourfold at 34 h, with macrophages comprising the most abundant cell
      lineage. There was no effect of SP on the number of oocytes ovulated; however,
      the weight of corpora lutea was increased in SP-treated gilts. SP also induced an
      increase in plasma progesterone content seen from day 5 to at least day 9 after
      treatment. In addition, granulosa cells and thecal tissue retrieved from
      preovulatory follicles of SP-treated gilts were more responsive in vitro to
      growth factor- and gonadotrophin-stimulated cell proliferation and progesterone
      synthesis. These results suggest that uterine exposure to SP influences immune
      cell trafficking in the ovary and enhances steroidogenesis in early pregnancy.
      The effects of SP on ovarian function potentially contribute to reproductive
      success in the pig.

PMID- 16816341
TI  - Differential glucocorticoid effects on proliferation and invasion of human
      trophoblast cell lines.
AB  - Several clinical situations require continuous glucocorticoid (GC) treatment
      during pregnancy. A well-known deleterious side effect of such treatment is the
      higher incidence of growth-restricted fetuses, for which a too shallow
      trophoblast invasion is presently hypothesised as the underlying cause. This
      study investigated whether the synthetic GC triamcinolone acetonide (TA)
      influences proliferation, invasion and endocrine activity of human trophoblast.
      BeWo and JEG-3 choriocarcinoma cell lines both express GC receptors (western
      blotting) and were used as models for human trophoblast. JAR devoid cells of GC
      receptor were used as negative control. The cells were cultured for 48 h without
      (control) or with 0.5, 5 and 50 microM TA. In the presence and absence of serum,
      proliferation was determined by cell counting and measuring the cell cycle
      regulating protein cyclin B1 (Western blotting); invasion was determined by a
      conventional Matrigel invasion assay and by measuring the secretion (ELISA) of
      matrix-metalloproteinases (MMP-2, MMP-9) into the culture medium; endocrine
      activity was assessed by measuring the levels of human chorionic gonadotropin
      (ELISA) into the culture medium. TA altered the number of viable and dead cells
      as well as cyclin B1 levels and, to a lesser extent, invasion of BeWo and JEG-3,
      with a strong influence of serum. BeWo and JEG-3 cells reacted differently and in
      most instances reverse. In the cell lines used as models of human trophoblast, TA
      alter some functions relevant to proliferation and invasion, and suggest that
      caution should be exercised when treating women with GCs during pregnancy.

PMID- 16816342
TI  - Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre
      eclamptic pregnancies and functional role in isoprostane-induced
      vasoconstriction.
AB  - Pre eclampsia represents a state of increased or prolonged vasoconstriction,
      partially linked to the potent vasocontractile effect of isoprostanes. The
      process of Rho A-mediated calcium sensitisation is inherent to a state of
      prolonged contractility in many smooth muscle types. The aim of this study was
      (1) to investigate mRNA expression levels of Rho A and Rho kinase isoforms (I and
      II) in the umbilical artery from normotensive and pre eclamptic women and (2) to
      determine whether the effects of two isoprostanes, 8-iso prostaglandin F(2alpha)
      (8-iso PGF2alpha) and 8-iso prostaglandin E(2) (8-iso PGE(2)), on umbilical
      artery tone, were mediated via the Rho kinase pathway. Real-time RT-PCR using
      primers for Rho A, ROCK I and ROCK II was performed on total RNA isolated from
      umbilical artery specimens obtained from normotensive and pre eclamptic women.
      The effects of both isoprostanes (n = 6) (in the absence and presence of the
      specific Rho kinase inhibitor Y-27632), on umbilical artery tone were measured,
      and compared with control recordings. Rho A mRNA expression levels were
      significantly lower in umbilical artery samples obtained from pre eclamptic women
      (n = 4) in comparison to those from normotensive women (n = 6) (P < 0.05). ROCK I
      and ROCK II mRNA levels were similar in both vessel types (P > 0.05). Both
      isoprostanes exerted a significant concentration-dependent vasocontractile effect
      (n = 7) (P < 0.001) on umbilical artery. For 8-iso PGE(2), this effect was
      antagonised by Y-27632 (n = 6) (P < 0.01). The significant reduction of Rho A
      mRNA levels in umbilical arteries from pregnancies complicated by pre eclampsia
      may serve to counteract the diminished perfusion associated with the
      pathophysiology of pre eclampsia. The vasocontractile effect of 8-iso PGE(2) in
      pre eclampsia may in part be mediated via the Rho kinase pathway.

PMID- 16816343
TI  - The use of interferon-gamma-based blood tests for the detection of latent
      tuberculosis infection.

PMID- 16816344
TI  - Integrated care: a new model for COPD management?

PMID- 16816345
TI  - Natriuretic peptide measurements as part of the diagnostic work-up in pleural
      effusions: an emerging concept?

PMID- 16816346
TI  - Cough: what's in a name?
AB  - The cough reflex (CR) and the expiration reflex (ER) are two defensive reflexes
      from the respiratory tract, the latter mainly from the larynx. Both are elicited
      by mechanical and chemical irritation of the airway mucosa, and are a
      characteristic of airway diseases, but they have different functions. The CR
      first draws air into the lungs, to accentuate the subsequent expulsive phase; the
      ER consists of a strong expiration, to prevent aspiration of material into the
      lungs. They have different sensory pathways, central nervous circuits, and
      physiological and pharmacological modulations. In practice, coughing often
      consists of a combination of the two reflexes, a cough bout, epoch or attack.
      Articles on cough usually do not distinguish between the two reflexes, or whether
      the coughs are single events or epochs; they usually only measure frequency of
      expiratory efforts, and neglect other aspects. Current methods for measuring and
      assessing cough are described, with indications of when the use of these methods
      may be important.

PMID- 16816347
TI  - Dyspnoea and hypoxaemia after lung surgery: the role of interatrial right-to-left
      shunt.
AB  - After lung surgery, some patients complain of unexplained increased dyspnoea
      associated with hypoxaemia. This clinical presentation may be due to an
      interatrial right-to-left shunt despite normal right heart pressure. Some of
      these patients show postural dependency of hypoxaemia, whereas others do not. In
      this article, the pathogenesis and mechanisms involved in this post-surgical
      complication are discussed, and the techniques used for confirmation and
      localisation of shunt are reported. An invasive technique, such as right heart
      catheterisation with angiography, was often used in the past as the diagnostic
      procedure for the visualisation of interatrial shunt. As to noninvasive
      techniques, a perfusion lung scan may be used as the first approach as it may
      detect the effect of the right-to-left shunt by visualising an extrapulmonary
      distribution of the radioactive tracer. The 100% oxygen breathing test could also
      be used to quantify the amount of right-to-left shunt. Particular emphasis is
      given to newer imaging modalities, such as transoesophageal echocardiography,
      which is minimally invasive but highly sensitive in clearly visualising the
      atrial septum anatomy. Finally, the approach to closure of the foramen ovale or
      atrial septal defect is discussed. Open thoracotomy was the traditional approach
      in the past. Percutaneous closure has now become the most used and effective
      technique for the repair of the interatrial anatomical malformation.

PMID- 16816348
TI  - Pharmacological strategies for self-management of asthma exacerbations.
AB  - Written action plans are effective within asthma self-management, but there are
      few guidelines about the specific medication adjustments which can be recommended
      for self-treatment of exacerbations. This review examines pharmacological
      strategies for self-management of asthma exacerbations in adults, including those
      for inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) users. Oral
      corticosteroids are well-established in clinical practice and clinical trials for
      the treatment of severe exacerbations, including during combination therapy.
      Evidence supports 7-10 days treatment, with no need to taper except to reduce
      side-effects. Doubling the dose of ICS is not effective. Several studies have
      shown benefit from high-dose ICS (2,400-4,000 microg beclomethasone equivalent)
      for 1-2 weeks. This may be achieved by adding a high-dose ICS inhaler to
      maintenance ICS or ICS/LABA therapy. There is inconclusive evidence about acutely
      increasing the dose of maintenance budesonide/formoterol for exacerbations, and
      no studies of this approach with fluticasone/salmeterol. For patients taking
      maintenance budesonide/formoterol, use of the same medication as-needed reduces
      exacerbations. Short-acting beta2-agonists are still effective in producing
      bronchodilation during combination therapy; however, a higher dose may be
      required. There is a need for further studies to clarify remaining issues about
      self-management of asthma exacerbations, particularly with regard to side-effects
      of treatment and patient acceptability.

PMID- 16816349
TI  - Place of cryotherapy, brachytherapy and photodynamic therapy in therapeutic
      bronchoscopy of lung cancers.
AB  - Cryotherapy, brachytherapy and photodynamic therapy (PDT) are three different
      methods proposed in the endoluminal treatment of lung cancers. The current
      article presents an overview of the specific indications and limits of each
      technique. These three methods were first proposed with palliative intent in
      inoperable patients with centrally located lung cancers. Now, the best indication
      is a curative intent in early stage lung cancers. Of the three, cryotherapy is
      the cheapest method. It induces cell necrosis in a 3-mm radius around the probe,
      and is suitable for treatment of superficial tumours. However, clinical trials
      are limited. In contrast, many clinical studies have confirmed the efficacy of
      PDT in treatment of superficial lung cancers. Brachytherapy can cure more
      aggressive tumours with deeper invasion into the bronchial wall. Unfortunately,
      no comparative studies have been published. Each of these methods induces a
      delayed tumour necrosis, and thus neither is indicated in the treatment of
      obstructive tumours with acute dyspnoea. In many situations, these methods should
      be complementary, particularly cryotherapy and brachytherapy or PDT and
      brachytherapy. The combination of these endoscopic methods with chemotherapy
      should be widely tested to promote the adjuvant role of the endoscopic methods in
      the treatment of lung cancers.

PMID- 16816350
TI  - Oxidative stress and redox regulation of lung inflammation in COPD.
AB  - Reactive oxygen species, either directly or via the formation of lipid
      peroxidation products, may play a role in enhancing inflammation through the
      activation of stress kinases (c-Jun activated kinase, extracellular signal
      regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear
      factor (NF)-kappaB and activator protein-1. This results in increased expression
      of a battery of distinct pro-inflammatory mediators. Oxidative stress activates
      NF-kappaB-mediated transcription of pro-inflammatory mediators either through
      activation of its activating inhibitor of kappaB-alpha kinase or the enhanced
      recruitment and activation of transcriptional co-activators. Enhanced NF-kappaB
      co-activator complex formation results in targeted increases in histone
      modifications, such as acetylation leading to inflammatory gene expression.
      Emerging evidence suggests the glutathione redox couple may entail dynamic
      regulation of protein function by reversible disulphide bond formation on
      kinases, phosphatases and transcription factors. Oxidative stress also inhibits
      histone deacetylase activity and in doing so further enhances inflammatory gene
      expression and may attenuate glucocorticoid sensitivity. The antioxidant/anti
      inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N
      acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane,
      cathechins/quercetin and reserveratol), specific spin traps, such as alpha-phenyl
      N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase
      (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound,
      eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all
      been shown to play a role in either controlling NF-kappaB activation or affecting
      histone modifications with subsequent effects on inflammatory gene expression in
      lung epithelial cells. Thus, oxidative stress regulates both key signal
      transduction pathways and histone modifications involved in lung inflammation.
      Various approaches to enhance lung antioxidant capacity and clinical trials of
      antioxidant compounds in chronic obstructive pulmonary disease are also
      discussed.

PMID- 16816351
TI  - Positional hyperventilation-induced hypoxaemia in pectus excavatum.
AB  - The presented case is of a young male (aged 19 yrs) with a pectus excavatum who
      showed significant exercise intolerance, despite normal pulmonary function at
      rest, including carbon monoxide diffusing capacity. Clinical exercise testing led
      to a strong suspicion of a right-to-left shunt due to an abnormally wide alveolo
      arterial oxygen gradient (26.4 kPa) at peak oxygen uptake, with severe arterial
      hypoxaemia (arterial oxygen tension 12.54 kPa). A right-to-left shunt was
      confirmed by transoesophageal echocardiography demonstrating a permeable foramen
      ovale, despite normal right heart pressures. The right-to-left venous flow was
      mainly dependent on the upright body position and the deep inspiration. Indeed,
      i.v. dobutamine infusion to selectively affect cardiac output and
      hyperventilation induced by tidal volume expansion at constant breathing rate in
      the supine position did not result in arterial oxygen desaturation or shunting.
      Closure of the foramen ovale through atrial umbrella placement dramatically
      improved clinical and physiological abnormalities. This observation demonstrates
      that a hyperventilatory manoeuvre in the upright position is able to detect a
      permeable foramen ovale favouring flow in the inferior vena cava in the direction
      of the abnormal pre-existing atrial channel in a patient with a pectus excavatum.

PMID- 16816352
TI  - A 53-year-old female with haemoptysis following breast cancer resection.

PMID- 16816353
TI  - The effect of gas standardisation on exhaled breath condensate pH.

PMID- 16816354
TI  - A physiological-social score for triaging of pandemic influenza patients.

PMID- 16816355
TI  - Video-assisted thoracic surgery and extramedullary haematopoiesis.

PMID- 16816356
TI  - Role of the Survivin gene in pathophysiology.
AB  - Although the roles of survivin in control of cancer cell division and apoptosis
      as well as targeting survivin for cancer therapeutics have been extensively
      explored and reviewed, the pathophysiological role of survivin in normal human
      cells/organs has not been deeply investigated or sufficiently reviewed. Studies
      in the latter area, however, appear to be important for the identification of
      different mechanisms of regulation and function of survivin in normal versus
      abnormal cells and tissues (including cancer), which might ultimately provide the
      basis for novel approaches for disease treatment with low toxicity. This Review
      is intended to summarize current observations in the literature related to the
      physiological and/or pathological roles for survivin in various normal human
      cells or organs. Our view of potential future research directions for survivin
      pertinent to potential therapeutic applications will also be discussed.

PMID- 16816357
TI  - Regulation of chemokine expression by NaCl occurs independently of cystic
      fibrosis transmembrane conductance regulator in macrophages.
AB  - Chronic pulmonary inflammation and infection are the leading causes of morbidity
      and mortality in cystic fibrosis (CF). While the effect of mutation of the cystic
      fibrosis transmembrane conductance regulator (CFTR) on airways remains
      controversial, some groups have demonstrated increases in Na(+) and Cl(-) in CF
      airway surface liquid compared to normal airways. We investigated the
      consequences of NaCl on pro-inflammatory chemokine and cytokine production by
      macrophages. Stimulation of mouse macrophages with increasing amounts of NaCl
      induced macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha
      (TNF-alpha) production. Further, co-incubation of macrophages with NaCl in the
      presence of either lipopolysaccharide (LPS) or TNF-alpha synergistically
      increased MIP-2 production. Both the NaCl and NaCl plus LPS responses were
      partially dependent on endogenous production and autocrine signaling by TNF
      alpha. To investigate the role of CFTR in MIP-2 production, we compared the
      responses of wild-type and DeltaF508 CF mouse macrophages to NaCl and LPS. The
      responses of macrophages from both strains were indistinguishable. In addition,
      CFTR mRNA was not expressed in macrophages. Taken together, these findings
      suggest that NaCl stimulates MIP-2 production by macrophages through a mechanism
      that is partially dependent on TNF-alpha but independent of macrophage CFTR
      expression.

PMID- 16816358
TI  - Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell
      disease.
AB  - In human and murine models of sickle cell disease (SCD), heme oxygenase-1 (HO-1)
      is induced in the kidney, an organ commonly involved in SCD. The present study
      assessed the role of HO-1 by using a competitive inhibitor of HO activity, tin
      protoporphyrin (SnPP), in protocols affording a composite, clinically relevant
      analysis of the kidney in SCD under unstressed and stressed conditions. Whereas
      short-term administration of SnPP exerted comparable renal hemodynamic effects in
      wild-type and sickle mice, chronic administration of SnPP exerted divergent
      effects: SnPP provoked tubulointerstitial inflammation and up-regulation of
      injury-related genes in wild-type mice, whereas in sickle mice SnPP reduced
      expression of injury-related genes and vascular congestion without provoking
      tubulointerstitial inflammation. SnPP also protected against the heightened
      sensitivity to renal ischemia observed in sickle mice, preventing ischemia
      induced worsening of renal injury in sickle mice above that observed in wild-type
      mice. Effective and comparable inhibition of HO activity by SnPP in wild-type and
      sickle mice was confirmed. These findings suggest that induction of HO-1, at
      least as assessed by this approach, may contribute to renal injury in this murine
      model of SCD and uncover an experimental maneuver that protects the kidney in
      murine SCD.

PMID- 16816359
TI  - Role for macrophage metalloelastase in glomerular basement membrane damage
      associated with alport syndrome.
AB  - Alport syndrome is a glomerular basement membrane (GBM) disease caused by
      mutations in type IV collagen genes. A unique irregular thickening and thinning
      of the GBM characterizes the progressive glomerular pathology. The metabolic
      imbalances responsible for these GBM irregularities are not known. Here we show
      that macrophage metalloelastase (MMP-12) expression is >40-fold induced in
      glomeruli from Alport mice and is markedly induced in glomeruli of both humans
      and dogs with Alport syndrome. Treatment of Alport mice with MMI270 (CGS27023A),
      a broad spectrum MMP inhibitor that blocks MMP-12 activity, results in largely
      restored GBM ultrastructure and function. Treatment with BAY-129566, a broad
      spectrum MMP inhibitor that does not inhibit MMP-12, had no effect. We show that
      inhibition of CC chemokine receptor 2 (CCR2) receptor signaling with
      propagermanium blocks induction of MMP-12 mRNA and prevents GBM damage. CCR2
      receptor is expressed in glomerular podocytes of Alport mice, suggesting MCP-1
      activation of CCR2 on podocytes may underlie induction of MMP-12. These data
      indicate that the irregular GBM that characterizes Alport syndrome may be
      mediated, in part, by focal degradation of the GBM due to MMP dysregulation, in
      particular, MMP-12. Thus, MMP-12/CCR2 inhibitors may provide a novel and
      effective therapeutic stra-tegy for Alport glomerular disease.

PMID- 16816360
TI  - Obligatory role for interleukin-13 in obstructive lesion development in airway
      allografts.
AB  - The pathogenesis of bronchiolitis obliterans (BO), a common and devastating
      obliterative disorder of small airways following lung transplantation, remains
      poorly understood. Lesions are characterized in their early stages by lymphocyte
      influx that evolves into dense fibrotic infiltrates. Airway specimens taken from
      patients with histological BO revealed infiltrating myofibroblasts, which
      strongly expressed the signaling chain of the high affinity interleukin-13 (IL
      13) receptor IL-13Ralpha1. Because IL-13 has proinflammatory and profibrotic
      actions, a contributory role for IL-13 in BO development was examined using
      murine models of orthotopic and heterotopic tracheal transplantation. Compared
      with airway isografts, allografts exhibited a significant increase in relative IL
      13 mRNA and protein levels. Allogeneic tracheas transplanted into IL-13-deficient
      mice were protected from BO in both transplant models. Flow cytometric analysis
      of orthotopic transplant tissue digests revealed markedly fewer infiltrating
      mononuclear phagocytes and CD3(+) T lymphocytes in IL-13-deficient recipients.
      Furthermore, protection from luminal obliteration, collagen deposition, and
      myofibroblast infiltration was observed in heterotopic airways transplanted into
      the IL-13(-/-) recipients. Transforming growth factor-beta1 expression was
      significantly decreased in tracheal allografts into IL-13(-/-) recipients,
      compared to wild-type counterparts. These human and murine data implicate IL-13
      as a critical effector cytokine driving cellular recruitment and subsequent
      fibrosis in clinical and ex-perimental BO.

PMID- 16816361
TI  - Bone morphogenetic protein-4 inhibitor gremlin is overexpressed in idiopathic
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF), ie, usual interstitial pneumonia in
      histopathology, is a disease characterized by tissue destruction and active areas
      of fibroproliferation in the lung. Gremlin (Drm), a member of the cysteine knot
      family of bone morphogenetic protein (BMP) inhibitors, functions to antagonize
      BMP-4-mediated signals during lung development. We describe here consistent
      overexpression of gremlin in the lung interstitium of IPF patients. Quantitative
      real-time reverse transcriptase-polymerase chain reaction analyses revealed
      considerably higher levels of gremlin mRNA in lung biopsies from IPF patients,
      the highest level being 35-fold higher compared to controls. Lung fibroblasts
      isolated from IPF patients also expressed elevated levels of gremlin, which was
      associated with impaired responsiveness to endogenous and exogenous BMP-4.
      Transforming growth factor-beta-induced epithelial-to-mesenchymal transition of
      A549 lung epithelial cells in culture was also associated with induction of
      gremlin mRNA expression. In addition, A549 cells transfected to overexpress
      gremlin were more susceptible to transforming growth factor-beta-induced
      epithelial-to-mesenchymal transition. Gremlin-mediated inhibition of BMP-4
      signaling pathways is likely to enhance the fibrotic response and reduce
      epithelial regeneration in the lung. The overexpression of this developmental
      gene in IPF may be a key event in the persistence of myofibroblasts in the lung
      interstitium and provides a potential target for therapeutic intervention.

PMID- 16816362
TI  - Cardiac conduction through engineered tissue.
AB  - In children, interruption of cardiac atrioventricular (AV) electrical conduction
      can result from congenital defects, surgical interventions, and maternal
      autoimmune diseases during pregnancy. Complete AV conduction block is typically
      treated by implanting an electronic pacemaker device, although long-term pacing
      therapy in pediatric patients has significant complications. As a first step
      toward developing a substitute treatment, we implanted engineered tissue
      constructs in rat hearts to create an alternative AV conduction pathway. We found
      that skeletal muscle-derived cells in the constructs exhibited sustained
      electrical coupling through persistent expression and function of gap junction
      proteins. Using fluorescence in situ hybridization and polymerase chain reaction
      analyses, myogenic cells in the constructs were shown to survive in the AV groove
      of implanted hearts for the duration of the animal's natural life. Perfusion of
      hearts with fluorescently labeled lec-tin demonstrated that implanted tissues
      became vascularized and immunostaining verified the presence of proteins
      important in electromechanical integration of myogenic cells with surrounding re
      cipient rat cardiomyocytes. Finally, using optical mapping and
      electrophysiological analyses, we provide evidence of permanent AV conduction
      through the implant in one-third of recipient animals. Our experiments provide a
      proof-of-principle that engineered tissue constructs can function as an
      electrical conduit and, ultimately, may offer a substitute treatment to
      conventional pacing therapy.

PMID- 16816364
TI  - Overexpression of the transcription factor GATA-3 enhances the development of
      pulmonary fibrosis.
AB  - Recent studies have demonstrated that Th2 cytokines, such as interleukin-4 and
      interleukin-13, enhance fibrotic processes by activating fibroblast proliferation
      and collagen production, whereas interferon-gamma, a Th1 cytokine, inhibits these
      processes. Th1 and Th2 cells both differentiate from common T precursor cells,
      with transcription factor GATA-3 a key regulator of Th2 differentiation. In the
      present study, therefore, we examined the effects of GATA-3 overexpression on the
      development of pulmonary fibrosis in a mouse model. Wild-type C57BL/6 mice and
      GATA-3-overexpressing (GATA-3-tg) mice of the same background were
      intratracheally treated with bleomycin. The survival rate after bleomycin was
      significantly decreased in GATA-3-tg mice compared with wild-type mice. The
      degree of pulmonary fibrosis was much greater in GATA-3-tg mice than in wild-type
      mice 28 days after bleomycin treatment. Lung interferon-gamma concentration was
      significantly decreased in GATA-3-tg mice compared with wild-type mice by 7 days
      after either saline or bleomycin treatment. The concentration of transforming
      growth factor-beta, a fibrogenic cytokine, was significantly higher in GATA-3-tg
      mice than in wild-type mice. Exogenous administration of interferon-gamma to GATA
      3-tg mice improved the degree of pulmonary fibrosis and thus increased survival.
      These results indicate that overexpression of GATA-3 enhances the development of
      pulmonary fibrosis, possibly by reducing interferon-gamma levels in the lung.

PMID- 16816363
TI  - Mining the acute respiratory distress syndrome proteome: identification of the
      insulin-like growth factor (IGF)/IGF-binding protein-3 pathway in acute lung
      injury.
AB  - To obtain a more complete protein profile of the airspace milieu in acute
      respiratory distress syndrome (ARDS) and to identify new mediators, we analyzed
      bronchoalveolar lavage fluid (BALF) by shotgun proteomics. Using BALF from three
      patients, we identified a total of 870 different proteins, a nearly 10-fold
      increase from previous reports. Among the proteins identified were known markers
      of lung injury, such as surfactant, proteases, and serum proteins. We also
      identified several biologically interesting proteins not previously identified in
      patients with ARDS, including insulin-like growth factor-binding protein-3 (IGFBP
      3). Because of the known role of IGFBP-3 in regulating cell survival, we measured
      IGFBP-3 levels by enzyme-linked immunosorbent assay in ARDS BALF. Normal controls
      had low levels of IGFBP-3, whereas patients with early ARDS had a significant
      increase in IGFBP-3. The IGF pathway, acting through the type 1 IGF-receptor,
      repressed apoptosis of lung fibroblasts but not lung epithelial cells.
      Furthermore, depletion of IGF in ARDS BALF led to enhanced fibroblast apoptosis.
      Our data suggest that the IGFBP-3/IGF pathway is involved in the pathogenesis of
      lung injury, illustrating the power of shotgun proteomics to catalog proteins
      present in complex biological fluids, such as BALF, from which hypotheses can be
      developed and tested.

PMID- 16816365
TI  - Cardiovascular expression of the mouse WNK1 gene during development and adulthood
      revealed by a BAC reporter assay.
AB  - Large deletions in WNK1 are associated with inherited arterial hypertension. WNK1
      encodes two types of protein: a kidney-specific isoform (KS-WNK1) lacking kinase
      activity and a ubiquitously expressed full-length isoform (L-WNK1) with serine
      threonine kinase activity. Disease is thought to result from hypermorphic
      mutations increasing the production of one or both isoforms. However, the pattern
      of L-WNK1 expression remains poorly characterized. We generated transgenic mice
      bearing a murine WNK1 BAC containing the nlacZ reporter gene for monitoring L
      WNK1 expression during development and adulthood. We observed previously
      unsuspected early expression in the vessels and primitive heart during
      embryogenesis, consistent with the early death of WNK1(-/-) mice. The generalized
      cardiovascular expression observed in adulthood may also suggest a possible
      kidney-independent role in blood pressure regulation. The second unsuspected site
      of L-WNK1 expression was the granular layer and Purkinje cells of the cerebellum,
      suggesting a role in local ion balance or cell trafficking. In the kidney,
      discordance between endogenous L-WNK1 and transgene expression suggests that
      either cis-regulatory elements important for physiological renal expression lie
      outside the BAC sequence or that illegitimate interactions occur between
      promoters. Despite this limitation, this transgenic model is a potentially
      valuable tool for the analysis of spatial and temporal aspects of WNK1 expression
      and regulation.

PMID- 16816366
TI  - Pro-NGF from Alzheimer's disease and normal human brain displays distinctive
      abilities to induce processing and nuclear translocation of intracellular domain
      of p75NTR and apoptosis.
AB  - The pro form of neurotrophic growth factor (pro-NGF), purified by chromatography
      from human Alzheimer's disease (AD)-affected brains (ADhbi-pro-NGF), has been
      shown to induce apoptotic cell death in neuronal cell cultures through its
      interaction with the p75 neurotrophin receptor (p75NTR). In the present work, we
      report that ADhbi-pro-NGF stimulates processing of p75NTR with alpha- and gamma
      secretases, yielding a 20-kd intracellular domain (p75(ICD)) that translocates to
      the nucleus. This process was accompanied by delayed apoptosis. In AD, p75(ICD)
      was significantly increased in human entorhinal cortex. Although human frontal
      cortex has been described as showing a higher pro-NGF increase in AD, the
      increase in the entorhinal cortex paralleled p75NTR processing in its
      intracellular domain. In addition, pro-NGF isolated from AD-affected brains
      differed functionally from pro-NGF isolated from comparably aged control brains,
      with pro-NGF isolated from control brains being unstable and undergoing
      degradation to NGF when added to cell culture. As p75(ICD) and pro-NGF are both
      mediators of apoptosis and are both found in increased levels in the cerebral
      cortex in AD, the present data have implications for understanding neuronal
      degeneration in AD.

PMID- 16816367
TI  - Photoreceptor cell apoptosis in the retinal degeneration of Uchl3-deficient mice.
AB  - UCH-L3 belongs to the ubiquitin C-terminal hydrolase family that deubiquitinates
      ubiquitin-protein conjugates in the ubiquitin-proteasome system. A murine Uchl3
      deletion mutant displays retinal degeneration, muscular degeneration, and mild
      growth retardation. To elucidate the function of UCH-L3, we investigated
      histopathological changes and expression of apoptosis- and oxidative stress
      related proteins during retinal degeneration. In the normal retina, UCH-L3 was
      enriched in the photoreceptor inner segment that contains abundant mitochondria.
      Although the retina of Uchl3-deficient mice showed no significant morphological
      abnormalities during retinal development, prominent retinal degeneration became
      manifested after 3 weeks of age associated with photoreceptor cell apoptosis.
      Ultrastructurally, a decreased area of mitochondrial cristae and vacuolar changes
      were observed in the degenerated inner segment. Increased immunoreactivities for
      manganese superoxide dismutase, cytochrome c oxidase I, and apoptosis-inducing
      factor in the inner segment indicated mitochondrial oxidative stress. Expression
      of cytochrome c, caspase-1, and cleaved caspase-3 did not differ between wild
      type and mutant mice; however, immunoreactivity for endonuclease G was found in
      the photoreceptor nuclei in the mutant retina. Hence, loss of UCH-L3 leads to
      mitochondrial oxidative stress-related photoreceptor cell apoptosis in a caspase
      independent manner. Thus, Uchl3-deficient mice represent a model for adult-onset
      retinal degeneration associated with mitochondrial impairment.

PMID- 16816368
TI  - L-asparaginase-induced antithrombin type I deficiency: implications for
      conformational diseases.
AB  - Serpinopathies, a group of diseases caused by mutations that disrupt the
      structurally sensitive serpins, have no known acquired cause. Interestingly, l
      asparaginase treatment of acute lymphoblastic leukemia patients causes severe
      deficiency in the serpin antithrombin. We studied the consequences of this drug
      on antithrombin levels, activity, conformation, and immunohistological and
      ultrastructural features in plasma from acute lymphoblastic leukemia patients,
      HepG2 cells, and plasma and livers from mice treated with this drug.
      Additionally, we evaluated intracellular deposition of alpha1-antitrypsin. l
      Asparaginase did not affect functional or conformational parameters of mature
      antithrombin; however, patients and mice displayed severe type I deficiency with
      no abnormal conformations of circulating antithrombin. Moreover, l-asparaginase
      impaired secretion of antithrombin by HepG2 cells. These effects were explained
      by the intracellular retention of antithrombin, forming aggregates within dilated
      endoplasmic reticulum cisterns. Similar effects were observed for alpha1
      antitrypsin in plasma, cells, and livers, and intracellular aggregates of
      additional proteins were observed in frontal cortex and pancreas. This is the
      first report of a conformational drug-associated effect on serpins without
      genetic factors involved. l-Asparaginase treatment induces severe, acquired, and
      transient type I deficiency of antithrombin (and alpha1-antitrypsin) with
      intracellular accumulation of the nascent molecule, increasing the risk of
      thrombosis.

PMID- 16816369
TI  - Chronically increased transforming growth factor-beta1 strongly inhibits
      hippocampal neurogenesis in aged mice.
AB  - There is increasing evidence that hippocampal learning correlates strongly with
      neurogenesis in the adult brain. Increases in neurogenesis after brain injury
      also correlate with improved outcomes. With aging the capacity to generate new
      neurons decreases dramatically, both under normal conditions and after injury.
      How this decrease occurs is not fully understood, but we hypothesized that
      transforming growth factor (TGF)-beta1, a cell cycle regulator that rapidly
      increases after injury and with age, might play a role. We found that chronic
      overproduction of TGF-beta1 from astrocytes almost completely blocked the
      generation of new neurons in aged transgenic mice. Even young adult TGF-beta1
      mice had 60% fewer immature, doublecortin-positive, hippocampal neurons than wild
      type littermate controls. Bromodeoxyuridine labeling of dividing cells in 2-month
      old TGF-beta1 mice confirmed this decrease in neuro-genesis and revealed a
      similar decrease in astrogenesis. Treatment of early neural progenitor cells with
      TGF-beta1 inhibited their proliferation. This strongly suggests that TGF-beta1
      directly affects these cells before their differentiation into neurons and
      astrocytes. Together, these data show that TGF-beta1 is a potent inhibitor of
      hippocampal neural progenitor cell proliferation in adult mice and suggest that
      it plays a key role in limiting injury and age-related neurogenesis.

PMID- 16816370
TI  - Inefficient chronic activation of parietal cells in Ae2a,b(-/-) mice.
AB  - In parietal cells, basolateral Ae2 Cl(-)/HCO(3)(-) exchanger (Slc4a2) appears to
      compensate for luminal H(+) pumping while providing Cl(-) for apical secretion.
      In mouse and rat, mRNA variants Ae2a, Ae2b1, Ae2b2, and Ae2c2 are all found in
      most tissues (although the latter at very low levels), whereas Ae2c1 is
      restricted to the stomach. We studied the acid secretory function of gastric
      mucosa in mice with targeted disruption of Ae2a, Ae2b1, and Ae2b2 (but not Ae2c)
      isoforms. In the oxyntic mucosa of Ae2(a,b)(-/-) mice, total Ae2 protein was
      nearly undetectable, indicating low gastric expression of the Ae2c isoforms. In
      Ae2(a,b)(-/-) mice basal acid secretion was normal, whereas carbachol/histamine
      stimulated acid secretion was impaired by 70%. These animals showed increased
      serum gastrin levels and hyperplasia of G cells. Immunohistochemistry and
      electron microscopy revealed baseline activation of parietal cells with fusion of
      intracellular H(+)/K(+)-ATPase-containing vesicles with the apical membrane and
      degenerative changes (but not substantial apoptosis) in a subpopulation of these
      cells. Increased expression of proliferating cell nuclear antigen in the oxyntic
      glands suggested enhanced Ae2(a,b)(-/-) parietal cell turnover. These data reveal
      a critical role of Ae2a-Ae2b1-Ae2b2 isoforms in stimulated gastric acid secretion
      whereas residual Ae2c isoforms could account to a limited extent for basal acid
      secretion.

PMID- 16816371
TI  - Protective effect of proteinase-activated receptor 2 activation on motility
      impairment and tissue damage induced by intestinal ischemia/reperfusion in
      rodents.
AB  - We hypothesized that proteinase-activated receptor-2 (PAR(2)) modulates
      intestinal injuries induced by ischemia/reperfusion. Ischemia (1 hour) plus
      reperfusion (6 hours) significantly delayed gastrointestinal transit (GIT)
      compared with sham operation. Intraduodenal injection of PAR(2)-activating
      peptide SLIGRL-NH(2) significantly accelerated transit in ischemia/reperfusion
      but not in sham-operated rats. GIT was significantly delayed in
      ischemia/reperfusion and sham-operated PAR(2)(-/-) mice compared with
      PAR(2)(+/+). SLIGRL-NH(2) significantly accelerated transit in
      ischemia/reperfusion in PAR(2)(+/+) but not in PAR(2)(-/-) mice. Prevention of
      mast cell degranulation with cromolyn, ablation of visceral afferents with
      capsaicin, and antagonism of calcitonin gene-related peptide (CGRP) and
      neurokinin-1 receptors with CGRP(8-37) and RP67580, respectively, abolished the
      SLIGRL-NH(2)-induced stimulatory effect on transit in ischemia/reperfusion.
      Tissue damage was significantly reduced by SLIGRL-NH(2); this effect was not
      observed in cromolyn-, capsaicin-, or RP67580-treated rats but was detected
      following CGRP(8-37). Intestinal PAR(2) mRNA levels were not affected by SLIGRL
      NH(2) in ischemia/reperfusion. We propose that PAR(2) modulates GIT and tissue
      damage in intestinal ischemia/reperfusion by a mechanism dependent on mast cells
      and visceral afferents. PAR(2) effect on transit might be mediated by CGRP and
      substance P, whereas the effect on tissue damage appears to involve substance P
      but not CGRP. PAR(2) might be a signaling system in the neuroimmune communication
      in intestinal ischemia/reperfusion.

PMID- 16816372
TI  - Role of neuronal interferon-gamma in the development of myelopathy in rats
      infected with human T-cell leukemia virus type 1.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of not only
      adult T-cell leukemia but also HTLV-1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). Among the rat strains infected with HTLV-1, chronic
      progressive myelopathy, named HAM rat disease, occurs exclusively in WKAH rats.
      In the present study, we found that HTLV-1 infection induces interferon (IFN)
      gamma production in the spinal cords of HAM-resistant strains but not in those of
      WKAH rats. Neurons were the major cells that produced IFN-gamma in HTLV-1
      infected, HAM-resistant strains. Administration of IFN-gamma suppressed
      expression of pX, the gene critically involved in the onset of HAM rat disease,
      in an HTLV-1-immortalized rat T-cell line, indicating that IFN-gamma protects
      against the development of HAM rat disease. The inability of WKAH spinal cord
      neurons to produce IFN-gamma after infection appeared to stem from defects in
      signaling through the interleukin (IL)-12 receptor. Specifically, WKAH-derived
      spinal cord cells were unable to up-regulate the IL-12 receptor beta2 gene in
      response to IL-12 stimulation. We suggest that the failure of spinal cord neurons
      to produce IFN-gamma through the IL-12 pathway is involved in the development of
      HAM rat disease.

PMID- 16816373
TI  - Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for
      capturing hepatitis C virus particles.
AB  - Hepatic sinusoidal endothelial cells are unique among endothelial cells in their
      ability to internalize and process a diverse range of antigens. DC-SIGNR, a type
      2 C-type lectin expressed on liver sinusoids, has been shown to bind with high
      affinity to hepatitis C virus (HCV) E2 glycoprotein. DC-SIGN is a closely related
      homologue reported to be expressed only on dendritic cells and a subset of
      macrophages and has similar binding affinity to HCV E2 glycoprotein. These
      receptors function as adhesion and antigen presentation molecules. We report
      distinct patterns of DC-SIGNR and DC-SIGN expression in human liver tissue and
      show for the first time that both C-type lectins are expressed on sinusoidal
      endothelial cells. We confirmed that these receptors are functional by
      demonstrating their ability to bind HCV E2 glycoproteins. Although these lectins
      on primary sinusoidal cells support HCV E2 binding, they are unable to support
      HCV entry. These data support a model where DC-SIGN and DC-SIGNR on sinusoidal
      endothelium provide a mechanism for high affinity binding of circulating HCV
      within the liver sinusoids allowing subsequent transfer of the virus to
      underlying hepatocytes, in a manner analogous to DC-SIGN presentation of human
      immunodeficiency virus on dendritic cells.

PMID- 16816374
TI  - Pathogenic role for virus-specific CD4 T cells in mice with coronavirus-induced
      acute encephalitis.
AB  - Acute viral encephalitis is believed to result from direct virus destruction of
      infected cells and from virus-induced host immune response, but the relative
      contribution of each remains largely unknown. For example, C57BL/6 (B6) mice
      infected with mouse hepatitis virus (JHM strain, JHMV) develop severe
      encephalitis, with death occurring within 7 days. Here, we show that the host
      response to a single JHMV-specific immunodominant CD4 T-cell epitope is critical
      for severe disease. We engineered a recombinant JHMV with mutations in the
      immunodominant CD4 T-cell epitope (rJ.M(Y135Q)). Infection of naive B6 mice with
      this virus resulted in mild disease with no mortality. However, introduction of a
      CD4 T-cell epitope from Listeria monocytogenes into rJ.M(Y135Q) generated a
      highly virulent virus. The decrease in disease severity was not due to a switch
      from Th1 to Th2 predominance in rJ.M(Y135Q)-infected mice, an effect on CD8 T
      cell function, or differential expression of tumor necrosis factor-alpha by JHMV
      specific CD4 T cells. These results show that the response to a single virus
      specific CD4 T-cell epitope may contribute to a pathogenic host response in the
      setting of acute viral disease and that abrogation of this response ameliorates
      clinical disease without diminishing virus clearance.

PMID- 16816375
TI  - Separate origins of hepatitis B virus surface antigen-negative foci and
      hepatocellular carcinomas in transgenic HBsAg (alb/psx) mice.
AB  - We have examined the development and transgene expression in liver lesions of
      transgenic mice bearing the hepatitis B surface antigen (HBsAg) gene of hepatitis
      B virus under the control of the albumin promoter (alb/psx) to study liver
      regeneration and hepatocellular carcinoma (HCC) associated with hepatitis B virus
      infection. Storage of the HBsAg in the endoplasmic reticulum precedes loss of
      liver cells and regenerative hyperplastic nodules that do not express HBsAg.
      Histological analysis indicated that HBsAg-negative foci and nodules arose from
      liver progenitor cells in the portal zone and lacked mRNA expression. Genomic DNA
      from eight of nine HBsAg-negative laser capture-excised liver foci showed loss of
      part of the alb/psx gene, whereas no loss of the actin gene was observed. The
      alb/psx DNA was intact in adjacent HBsAg-positive tissue. Sequencing of
      polymerase chain reaction products suggested that alterations in the HBsAg
      transgene in HBsAg-negative foci occurred via large-scale deletions as opposed to
      single-site mutations. Southern blot analysis of HCC from 2-year-old transgenic
      HBsAg mice, however, revealed an intact alb/psx gene. Thus, HBsAg-negative
      progenitor cells with deletions in the transgene appear to be responsible for
      compensatory regeneration of the liver, whereas HCCs arise from clonal expansion
      of hepatocytes with intact alb/psx transgenes.

PMID- 16816376
TI  - Role of the integrin-binding protein osteopontin in lymphatic metastasis of
      breast cancer.
AB  - Although a primary route of breast cancer metastasis is believed to be via
      lymphatics, the molecular factors involved are poorly understood. We hypothesized
      that one such factor may be the integrin-binding protein osteopontin (OPN), and
      we investigated this clinically and experimentally. In breast cancer patients
      undergoing sentinel lymph node biopsy, OPN levels were significantly higher in
      lymph node metastases than in the primary tumor (P < 0.001). To test the
      functional contribution of OPN to lymphatic metastasis and to determine whether
      the RGD (Arg-Gly-Asp) integrin-binding sequence of OPN is important for this
      process, we transfected wild-type OPN or mutant OPN (lacking the RGD sequence)
      into MDA-MB-468 human breast cancer cells. In vitro, cells overexpressing OPN
      demonstrated increased anchorage-independent growth in soft agar (P = 0.001) and
      increased RGD-dependent adhesion (P = 0.045). Following mammary fat pad injection
      of nude mice, cells overexpressing OPN showed increased lymphovascular invasion,
      lymph node metastases, and lung micrometastases at earlier time points (P =
      0.024). Loss of the RGD region partially abrogated this effect in the lymphatics
      (P = 0.038). These novel findings indicate that OPN is a key molecular player
      involved in lymphatic metastasis of breast cancer, potentially by affecting RGD
      mediated adhesive interactions and by enhancing the establishment/persistence of
      tumor cells in the lymphatics.

PMID- 16816377
TI  - Concurrent expression of hyaluronan biosynthetic and processing enzymes promotes
      growth and vascularization of prostate tumors in mice.
AB  - Aggressive cells in prostate cancer secrete extracellular hyaluronan (HA) as a
      result of up-regulated HA synthase enzymes HAS2 and HAS3. Combined detection of
      HA and the HA processing hyaluronidase enzyme Hyal1 in prostate tumors correlates
      with poor outcome. HA oligomers produced by hyaluronidases are potent angiogenic
      stimuli. We investigated the respective roles of HAS2 and Hyal1 using 22Rv1 human
      prostate tumor cells that lack both enzyme activities. Stable transfectants were
      selected for overexpression of Hyal1 or HAS2 and for coexpression of Hyal1 and
      HAS2. HAS2 overexpression elevated HA production and excess pericellular HA
      retention. However, HAS2-transfected tumor cell growth in culture was
      dramatically slowed. Coexpression of Hyal1 with HAS2 diminished HA retention but
      restored growth kinetics, supporting a possible combined role for excess HA
      synthesis and processing in maximizing unrestricted growth of prostate cancer
      cells. In mice, overexpression of HAS2 increased subcutaneous tumor size. Excess
      activity of either Hyal1 or HAS2 enhanced angiogenesis, but the most significant
      tumorigenic potential was realized by coexpression of both Hyal1 and HAS2
      enzymes. Thus, HA production by tumor cells in prostate cancer may enhance the
      aggressive potential of the cells by increasing Hyal1-dependent autocrine
      proliferation and potentiating vascular development.

PMID- 16816378
TI  - Disabled-2 heterozygous mice are predisposed to endometrial and ovarian
      tumorigenesis and exhibit sex-biased embryonic lethality in a p53-null
      background.
AB  - Disabled-2 (Dab2) is a phosphoprotein involved in cellular signal transduction
      and endocytic trafficking. The expression of Dab2 is frequently lost or
      suppressed in several epithelial tumors, and studies of its cellular function and
      growth suppressive activity when re-expressed in cancer cells led to the
      suggestion that Dab2 is a tumor suppressor. A role for Dab2 in epithelial cell
      positioning organization was derived from study of knockout mice: homozygous
      deletion of dab2 results in early embryonic lethality due to the disorganization
      of the primitive endoderm, the first epithelium in early embryos. We now report
      that dab2 heterozygous mice develop uterine hyperplasia and ovarian preneoplastic
      morphological changes at a high frequency. Crossing into a p53(-/-) background
      unexpectedly produced few female dab2(+/-):p53(-/-) mice, while the male dab2(+/
      ):p53(-/-) were born at the expected Mendelian frequency. The tumor-prone
      phenotype of dab2(+/-) mice provides additional support for a role of human Dab2
      as a tumor suppressor, and the sex-biased embryonic lethality suggests a genetic
      interaction between p53 and dab2 genes in female mice.

PMID- 16816379
TI  - Protease-activated receptor-2 activation in gastric cancer cells promotes
      epidermal growth factor receptor trans-activation and proliferation.
AB  - Dysregulated epidermal growth factor receptor (EGFR) signaling is involved in
      gastric cancer (GC) cell growth. However, the mechanism that sustains EGFR
      signaling in GC remains unknown. Since protease-activated receptor-2 (PAR-2), a G
      protein-coupled receptor, has been shown to trans-activate EGFR in several cell
      types, we examined the role of PAR-2 in GC. We show here that in vitro activation
      of PAR-2 enhances the growth of two GC cell lines, AGS and MKN28. In both these
      cell lines, PAR-2 trans-activated EGFR and inhibition of EGFR tyrosine kinase
      activity by AG1478 or specific EGFR siRNA completely prevented PAR-2-driven
      proliferation. Antibody blockade of EGF-like ligands to EGFR did not modify EGFR
      signaling or cell growth induced by PAR-2 activation. In contrast, PAR-2 promoted
      Src activation and interaction of this kinase with EGFR. In support of this,
      inhibition of Src kinase activity by PP1 or siRNA blocked PAR-2-induced EGFR
      signaling cascade and cell growth. Finally, PAR-2 was detectable in both normal
      and GC specimens, but its expression was more pronounced in GC than controls and
      correlated with activated EGFR. These data show that PAR-2 is overexpressed in GC
      and suggest a role of PAR-2 in EGFR trans-activation and cell growth.

PMID- 16816380
TI  - Receptor tyrosine kinase EphB4 is a survival factor in breast cancer.
AB  - EphB4, a member of the largest family of receptor tyrosine kinases, is normally
      expressed on endothelial and neuronal cells. Although aberrant expression of
      EphB4 has been reported in several human tumors, including breast cancer, its
      functional significance is not understood. We report here that EphB4 is expressed
      in 7 of 12 (58%) human breast cancer specimens and 4 of 4 (100%) breast tumor
      cell lines examined. Overexpression of EphB4 in breast cancer cells was driven by
      gene amplification and by the erbB family of receptors via activation of Janus
      tyrosine kinase-signal transducers and activators of transcription and protein
      kinase B. The aberrantly expressed receptor was phosphorylated by its natural
      ligand, EphrinB2, and signaled via the protein kinase B pathway. Targeted
      knockdown of EphB4 expression by small interference RNA (and antisense
      oligodeoxynucleotides (ODNs)) led to dose-dependent reduction in cell survival,
      increased apoptosis, and sensitization to tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). Antisense ODN-mediated EphB4 knockdown resulted in
      reduced tumor growth in a murine tumor xenograft model. Antisense ODN-treated
      tumors were 72% smaller than control tumors at 6 weeks, with an 86% reduction in
      proliferating cells, 15-fold increase in apoptosis, and 44% reduction in tumor
      microvasculature. Our data indicate that biologically active EphB4 functions as a
      survival factor in breast cancer and is a novel target for therapy.

PMID- 16816381
TI  - The role of nicotinamide adenine dinucleotide phosphate oxidase-derived reactive
      oxygen species in the acquisition of metastatic ability of tumor cells.
AB  - We examined the role of phagocyte-derived oxygen radicals in tumor cell
      acquisition of metastatic phenotype by comparing gp91(phox-/-) mice and C57BL/6J
      wild-type (WT) mice. The gp91(phox-/-) mouse is deficient in the gp91(phox) gene,
      an essential subunit of the phagocyte nicotinamide adenine dinucleotide phosphate
      oxidase that generates superoxide anion. QR-32 fibrosarcoma cells are
      nonmetastatic but are converted into metastatic tumors once in contact with
      foreign body (gelatin sponge)-induced phagocytes in vivo. Compared to QR-32 cells
      co-implanted with the foreign body in WT mice, those in gp91(phox-/-) mice
      exhibited reduced metastasis. There was no difference in the incidence of primary
      tumors after injection of B16BL6 melanoma cells in WT and gp91(phox-/-) mice.
      However, after resection of the primary tumors, metastases were reduced in
      gp91(phox-/-) mice. Thymosin beta4 gene expression and cell motility/invasion
      were seen in the tumors from WT mice but not in those from gp91(phox-/-) mice.
      Adoptive transfer of phagocytes from WT mice, but not those from gp91(phox-/-)
      mice, restored the metastatic ability of tumors grown in gp91(phox-/-) mice.
      These findings show that tumor metastatic behavior can primarily be endowed by
      phagocyte-derived superoxide anion and its oxidative metabolites, which are
      generated through activation of nicotinamide adenine dinucleotide phosphate
      oxidase.

PMID- 16816382
TI  - Reduced acute vascular injury and atherosclerosis in hyperlipidemic mice
      transgenic for lysozyme.
AB  - Hyperlipidemia promotes oxidant stress, inflammation, and atherogenesis in
      apolipoprotein E-deficient (ApoE((-/-))) mice. Mice transgenic for lysozyme (LZ
      Tg) are resistant to acute and chronic oxidative stress and have decreased
      circulating levels of pro-oxidant advanced glycation end-products (AGEs). Herein
      we report that TIB-186 macrophages transduced with adenovirus-expressing human LZ
      (AdV-LZ) containing the AGE-binding domain facilitated AGE uptake and degradation
      and that AdV-LZ-transduced macrophages and peritoneal macrophages from LZ-Tg mice
      suppressed the AGE-triggered tumor necrosis factor-alpha response. We assessed
      atherosclerosis in LZ-Tg mice crossed with ApoE((-/-)) mice (LZ/ApoE((-/-))) and
      found increased serum LZ levels and decreased AGE and 8-isoprostanes levels,
      although hyperlipidemia remained similar to ApoE((-/-)) controls. Atherosclerotic
      plaques and neointimal lesions at the aortic root and descending aorta were
      markedly decreased (by 40% and 80%, respectively) in LZ/ApoE((-/-)) versus ApoE((
      /-)) mice, as were inflammatory infiltrates. The arterial lesions following
      femoral artery injury in LZ/ApoE((-/-)) mice were suppressed (intimal to media
      ratio decreased by 50%), as were AGE deposits and vascular smooth muscle cell
      activation, compared to ApoE((-/-)) mice. Despite hyperlipidemia, development of
      atheroma and occlusive, inflammatory arterial neointimal lesions in response to
      injury was suppressed in LZ/ApoE((-/-)) mice. This effect may be due to the
      antioxidant properties of LZ, which is possibly linked to the AGE-binding domain
      region of the molecule.

PMID- 16816383
TI  - PECAM-1 affects GSK-3beta-mediated beta-catenin phosphorylation and degradation.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) regulates a variety
      of endothelial and immune cell biological responses. PECAM-1-null mice exhibit
      prolonged and increased permeability after inflammatory insults. We observed that
      in PECAM-1-null endothelial cells (ECs), beta-catenin remained tyrosine
      phosphorylated, coinciding with a sustained increase in permeability. Src
      homology 2 domain containing phosphatase 2 (SHP-2) association with beta-catenin
      was diminished in PECAM-1-null ECs, suggesting that lack of PECAM-1 inhibits the
      ability of this adherens junction component to become dephosphorylated, promoting
      a sustained increase in permeability. beta-Catenin/Glycogen synthase kinase 3
      (GSK-3beta) association and beta-catenin serine phosphorylation levels were
      increased and beta-catenin expression levels were reduced in PECAM-1-null ECs.
      Glycogen synthase kinase 3 (GSK-3beta) serine phosphorylation (inactivation) was
      blunted in PECAM-1-null ECs after histamine treatment or shear stress. Our data
      suggest that PECAM-1 serves as a critical dynamic regulator of endothelial
      barrier permeability. On stimulation by a vasoactive substance or shear stress,
      PECAM-1 became tyrosine phosphorylated, enabling recruitment of SHP-2 and
      tyrosine-phosphorylated beta-catenin to its cytoplasmic domain, facilitating
      dephosphorylation of beta-catenin, and allowing reconstitution of adherens
      junctions. In addition, PECAM-1 modulated the levels of beta-catenin by
      regulating the activity of GSK-3beta, which in turn affected the serine
      phosphorylation of beta-catenin and its proteosomal degradation, affecting the
      ability of the cell to reform adherens junctions in a timely fashion.

PMID- 16816385
TI  - Similarities and differences between cyclobutane pyrimidine dimer photolyase and
      (6-4) photolyase as revealed by resonance Raman spectroscopy: Electron transfer
      from the FAD cofactor to ultraviolet-damaged DNA.
AB  - The cyclobutane pyrimidine dimer (CPD) and (6-4) photoproduct, two major types of
      DNA damage caused by UV light, are repaired under illumination with near UV
      visible light by CPD and (6-4) photolyases, respectively. To understand the
      mechanism of DNA repair, we examined the resonance Raman spectra of complexes
      between damaged DNA and the neutral semiquinoid and oxidized forms of (6-4) and
      CPD photolyases. The marker band for a neutral semiquinoid flavin and band I of
      the oxidized flavin, which are derived from the vibrations of the benzene ring of
      FAD, were shifted to lower frequencies upon binding of damaged DNA by CPD
      photolyase but not by (6-4) photolyase, indicating that CPD interacts with the
      benzene ring of FAD directly but that the (6-4) photoproduct does not. Bands II
      and VII of the oxidized flavin and the 1398/1391 cm(-1) bands of the neutral
      semiquinoid flavin, which may reflect the bending of U-shaped FAD, were altered
      upon substrate binding, suggesting that CPD and the (6-4) photoproduct interact
      with the adenine ring of FAD. When substrate was bound, there was an upshifted
      1528 cm(-1) band of the neutral semiquinoid flavin in CPD photolyase, indicating
      a weakened hydrogen bond at N5-H of FAD, and band X seemed to be downshifted in
      (6-4) photolyase, indicating a weakened hydrogen bond at N3-H of FAD. These Raman
      spectra led us to conclude that the two photolyases have different electron
      transfer mechanisms as well as different hydrogen bonding environments, which
      account for the higher redox potential of CPD photolyase.

PMID- 16816386
TI  - Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase
      activation both in vitro and in vivo and protects against Clostridium difficile
      toxin A-induced enteritis.
AB  - Saccharomyces boulardii (Sb), a probiotic yeast, protects against intestinal
      injury and inflammation caused by a wide variety of enteric pathogens, including
      Clostridium difficile. Given the broad range of protective effects of Sb in
      multiple gastrointestinal disorders, we hypothesize that Sb modulates host
      signaling pathways involved in intestinal inflammatory responses. In this study,
      we found that Sb culture supernatant (SbS) inhibits interleukin-8 production
      induced by C. difficile toxin A or IL-1beta in human colonocyte NCM460 cells in a
      dose-dependent fashion. Furthermore, SbS inhibited IL-1beta and toxin A induced
      Erk1/2 and JNK/SAPK but not p38 activation in NCM460 cells. To test whether this
      inhibition also occurs in vivo, we used a previously established mouse ileal loop
      model. On its own, SbS had no significant effect on basal fluid secretion or
      intestinal histology. However, Erk1/2 activation was significantly inhibited by
      SbS in toxin A exposed mouse ileal mucosa. In control loops, toxin A increased
      fluid secretion (2.2-fold), histological score (3.3-fold), and levels of the
      chemokine KC (4.5-fold). SbS pretreatment completely normalized toxin A mediated
      fluid secretion (p < 0.01), and histopathologic changes (p < 0.01) and
      substantially inhibited toxin A-associated KC increases (p < 0.001). In summary,
      the probiotic yeast S. boulardii inhibits C. difficile toxin A-associated
      enteritis by blocking the activation of Erk1/2 MAP kinases. This study indicates
      a new mechanism whereby Sb protects against intestinal inflammation and supports
      the hypothesis that Sb modulates host inflammatory signaling pathways to exert
      its beneficial effects.

PMID- 16816384
TI  - Involvement of endothelial CD44 during in vivo angiogenesis.
AB  - CD44, a cell-surface receptor for hyaluronan, has been implicated in endothelial
      cell functions, but its role in the formation of blood vessels in vivo has not
      been established. In CD44-null mice, vascularization of Matrigel implants and
      tumor and wound angiogenesis were inhibited. Leukocyte accumulation during tumor
      growth and wound healing in wild-type and CD44-null mice were comparable, and
      reconstitution of CD44-null mice with wild-type bone marrow did not restore the
      wild-type phenotype, suggesting that impairments in angiogenesis in CD44
      deficient mice are due to the loss of endothelial CD44. Although the cell
      proliferation, survival, and wound-induced migration of CD44-null endothelial
      cells were intact, these cells were impaired in their in vitro ability to form
      tubes. Nascent vessels in Matrigel implants from CD44-null mice demonstrated
      irregular luminal surfaces characterized by retracted cells and thinned
      endothelia. Further, an anti-CD44 antibody that disrupted in vitro tube formation
      induced hemorrhage around Matrigel implants, suggesting that antagonism of
      endothelial CD44 undermined the integrity of the endothelium of nascent vessels.
      These data establish a role for CD44 during in vivo angiogenesis and suggest that
      CD44 may contribute to the organization and/or stability of developing
      endothelial tubular networks.

PMID- 16816387
TI  - Observed instability of T7 RNA polymerase elongation complexes can be dominated
      by collision-induced "bumping".
AB  - T7 RNA polymerase elongates RNA at a relatively high rate and can displace many
      tightly bound protein-DNA complexes. Despite these properties, measurements of
      the stability of stalled elongation complexes have shown lifetimes that are much
      shorter than those of the multisubunit RNA polymerases. In this work, we
      demonstrate that the apparent instability of stalled complexes actually arises
      from the action of trailing RNA polymerases (traveling in the same direction)
      displacing the stalled complex. Moreover, the instability caused by collision
      between two polymerases is position dependent. A second polymerase is blocked
      from promoter binding when a leading complex is stalled 12 bp or less from the
      promoter. The trailing complex can bind and make abortive transcripts when the
      leading complex is between 12 and 20 bp from the promoter, but it cannot displace
      the first complex since it is in a unstable initiation conformation. Only when
      the leading complex is stalled more than 20 bp away from the promoter can a
      second polymerase bind, initiate, and displace the leading complex.

PMID- 16816388
TI  - Nucleotide misincorporation, 3'-mismatch extension, and responses to abasic sites
      and DNA adducts by the polymerase component of bacterial DNA ligase D.
AB  - DNA ligase D (LigD) participates in a mutagenic pathway of nonhomologous end
      joining in bacteria. LigD consists of an ATP-dependent ligase domain fused to a
      polymerase domain (POL) and a phosphoesterase module. The POL domain performs
      templated and nontemplated primer extension reactions with either dNTP or rNTP
      substrates. Here we report that Pseudomonas LigD POL is an unfaithful nucleic
      acid polymerase. Although the degree of infidelity in nucleotide incorporation
      varies according to the mispair produced, we find that a correctly paired
      ribonucleotide is added to the DNA primer terminus more rapidly than the
      corresponding correct deoxyribonucleotide and incorrect nucleotides are added
      much more rapidly with rNTP substrates than with dNTPs, no matter what the
      mispair configuration. We find that 3' mispairs are extended by LigD POL, albeit
      more slowly than 3' paired primer-templates. The magnitude of the rate effect on
      mismatch extension varies with the identity of the 3' mispair, but it was
      generally the case that mispaired ends were extended more rapidly with rNTP
      substrates than with dNTPs. These results lend credence to the suggestion that
      LigD POL might fill in short 5'-overhangs with ribonucleotides when repairing
      double strand breaks in quiescent cells. We report that LigD POL can add a
      deoxynucleotide opposite an abasic lesion in the template strand, albeit slowly.
      Ribonucleotides are inserted more rapidly at an abasic lesion than are deoxys.
      LigD POL displays feeble activity in extending a preformed primer terminus
      opposing an abasic site, but can readily bypass the lesion by slippage of the
      primer 3' di- or trinucleotide and realignment to the template sequence distal to
      the abasic site. Covalent benzo[a]pyrene-dG and benzo[c]phenanthrene-dA adducts
      in the template strand are durable roadblocks to POL elongation. POL can slowly
      insert a dNMP opposite the adduct, but is impaired in the subsequent extension
      step.

PMID- 16816389
TI  - Pescadillo interacts with the cadmium response element of the human heme
      oxygenase-1 promoter in renal epithelial cells.
AB  - Renal tubular cells elicit adaptive responses following exposure to nephrotoxins,
      such as cadmium. One response is the up-regulation of the 32-kDa redox-sensitive
      protein, heme oxygenase-1. Exposure of renal proximal tubular epithelial cells to
      10 mum cadmium demonstrated induction ( approximately 20-fold) of heme oxygenase
      1 mRNA and protein. Using a 4.5-kb human heme oxygenase-1 promoter construct, the
      importance of a previously identified cadmium response element (TGCTAGAT) in HeLa
      cells was verified in renal epithelial cells. Specific protein-DNA interaction
      with this sequence was demonstrated using nuclear extracts from cadmium-treated
      cells. Yeast one-hybrid screen of a human kidney cDNA library resulted in the
      identification of pescadillo, a unique nucleolar, developmental protein, as an
      interacting protein with the cadmium response element and was confirmed by
      chromatin immunoprecipitation in vivo and gel shift assays with purified
      glutathione S-transferase-pescadillo protein in vitro. The specificity of the DNA
      protein interaction was verified by the absence of a binding complex when the
      core sequence of the cadmium response element was mutated or deleted. In
      addition, B23/nucleophosmin, another nucleolar protein, did not interact with the
      cadmium response sequence. Overexpression of pescadillo resulted in increased
      activity of the 4.5-kb human heme oxygenase-1 promoter construct but failed to
      activate this construct when the cadmium response sequence was mutated. The
      findings demonstrate the important and previously unrecognized role of pescadillo
      as a DNA-binding protein interacting specifically with the cadmium response
      element of the human heme oxygenase-1 gene.

PMID- 16816390
TI  - The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb
      girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB
      induced keratinocyte apoptosis through NFkappaB.
AB  - Protein inhibitors of activated STATs (PIAS) family members are ubiquitin-protein
      isopeptide ligase-small ubiquitin-like modifier ligases for diverse transcription
      factors. However, the regulation of PIAS protein activity in cells is poorly
      understood. Previously, we reported that expression of Trim32, a RING domain
      ubiquitin-protein isopeptide ligase-ubiquitin ligase mutated in human limb-girdle
      muscular dystrophy type 2H (LGMD2H) and Bardet-Biedl syndrome, is elevated during
      mouse skin carcinogenesis, protecting keratinocytes from apoptosis induced by UVB
      and tumor necrosis factor-alpha (TNFalpha). Here we report that Trim32 interacts
      with Piasy and promotes Piasy ubiquitination and degradation. Ubiquitination of
      Piasy by Trim32 could be reproduced in vitro using purified components. Their
      interaction was induced by treatment with UVB/TNFalpha and involved
      redistribution of Piasy from the nucleus to the cytoplasm, where it accumulated
      in cytoplasmic granules that colocalized with Trim32. Piasy destabilization and
      ubiquitination required an intact RING domain in Trim32. The LGMD2H-associated
      missense point mutation prevented Trim32 binding to Piasy, and human Piasy failed
      to colocalize with human Trim32 in fibroblasts isolated from an LGMD2H patient.
      Trim32 expression increased the transcriptional activity of NFkappaB in epidermal
      keratinocytes, both under basal treatment and after UVB/TNFalpha treatment.
      Conversely, Piasy inhibited NFkappaB activity under the same conditions and
      sensitized keratinocytes to apoptosis induced by TNFalpha and UVB. Our results
      indicate that, by controlling Piasy stability, Trim32 regulates UVB-induced
      keratinocyte apoptosis through induction of NFkappaB and suggests loss of
      function of Trim32 in LGMD2H.

PMID- 16816391
TI  - A systematic review of prion therapeutics in experimental models.
AB  - Prion diseases are transmissible, invariably fatal, neurodegenerative diseases
      which include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform
      encephalopathy and scrapie in animals. A large number of putative treatments have
      been studied in experimental models over the past 30 years, with at best modest
      disease-modifying effects. The arrival of variant CJD in the UK in the 1990s has
      intensified the search for effective therapeutic agents, using an increasing
      number of animal, cellular and in vitro models with some recent promising proof
      of principle studies. Here, for the first time, we present a comprehensive
      systematic, rather than selective, review of published data on experimental
      approaches to prion therapeutics to provide a scientific resource for informing
      future therapeutics research, both in laboratory models and in clinical studies.

PMID- 16816392
TI  - Determinants of diagnostic investigation sensitivities across the clinical
      spectrum of sporadic Creutzfeldt-Jakob disease.
AB  - To validate the provisional findings of a number of smaller studies and explore
      additional determinants of characteristic diagnostic investigation results across
      the entire clinical spectrum of sporadic Creutzfeldt-Jakob disease (CJD), an
      international collaborative study was undertaken comprising 2451 pathologically
      confirmed (definite) patients. We assessed the influence of age at disease onset,
      illness duration, prion protein gene (PRNP) codon 129 polymorphism (either
      methionine or valine) and molecular sub-type on the diagnostic sensitivity of
      EEG, cerebral MRI and the CSF 14-3-3 immunoassay. For EEG and CSF 14-3-3 protein
      detection, we also assessed the influence of the time point in a patient's
      illness at which the investigation was performed on the likelihood of a typical
      or positive result. Analysis included a large subset of patients (n = 743) in
      whom molecular sub-typing had been performed using a combination of the PRNP
      codon 129 polymorphism and the form of protease resistant prion protein [type 1
      or 2 according to Parchi et al. (Parchi P, Giese A, Capellari S, Brown P, Schulz
      Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A,
      Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H.
      Classification of sporadic Creutzfeldt-Jakob disease based on molecular and
      phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.)] present in
      the brain. Findings for the whole group paralleled the subset with molecular sub
      typing data available, showing that age at disease onset and disease duration
      were independent determinants of typical changes on EEG, while illness duration
      significantly influenced positive CSF 14-3-3 protein detection; changes on brain
      MRI were not influenced by either of these clinical parameters, but overall,
      imaging data were less complete and consequently conclusions are more tentative.
      In addition to age at disease onset and illness duration, molecular sub-type was
      re-affirmed as an important independent determinant of investigation results. In
      multivariate analyses that included molecular sub-type, time point of the
      investigation during a patient's illness was found not to influence the
      occurrence of a typical or positive EEG or CSF 14-3-3 protein result. A typical
      EEG was most often seen in MM1 patients and was significantly less likely in the
      MV1, MV2 and VV2 sub-types, whereas VV2 patients had an increased likelihood of a
      typical brain MRI. Overall, the CSF 14-3-3 immunoassay was the most frequently
      positive investigation (88.1%) but performed significantly less well in the very
      uncommon MV2 and MM2 sub-types. Our findings confirm a number of determinants of
      principal investigation results in sporadic CJD and underscore the importance of
      recognizing these pre-test limitations before accepting the diagnosis excluded or
      confirmed. Combinations of investigations offer the best chance of detection,
      especially for the less common molecular sub-types such as MV2 and MM2.

PMID- 16816393
TI  - Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on
      D2-receptor binding.
AB  - Clinical observations support a central role of the dopamine system in restless
      legs syndrome (RLS) but previous imaging studies of striatal dopamine D2
      receptors have yielded inconclusive results. Extrastriatal dopaminergic function
      has hitherto not been investigated. Sixteen RLS patients naive to dopaminergic
      drugs and sixteen matched control subjects were examined with PET.
      [11C]Raclopride and [11C]FLB 457 were used to estimate D2-receptor availability
      in striatum and extrastriatal regions, respectively. Examinations were performed
      both in the morning (starting between 10:00 and 12:00 h) and evening (starting at
      18:00 h). Measures were taken to monitor and control for head movement during
      data acquisition. In the striatum, patients had significantly higher
      [11C]raclopride binding potential (BP) values than controls. In extrastriatal
      regions, [11C]FLB 457 BP was higher in patients than controls, and in the
      regional analysis the difference was statistically significant in subregions of
      thalamus and the anterior cingulate cortex. The diurnal variability in BP with
      [11C]FLB 457 and [11C]raclopride was within the previously reported test-retest
      reproducibility for both radioligands. The study supports involvement of the
      dopamine system in both striatal and extrastriatal brain regions in the
      pathophysiology of RLS. The brain regions where differences in D2-receptor
      binding were shown are implicated in the regulation of affective and motivational
      aspects of sensory processing, suggesting a possible pathway for sensory symptoms
      in RLS. Increased D2-receptor availability in RLS may correspond to higher
      receptor densities or lower levels of endogenous dopamine. Both interpretations
      are consistent with the hypothesis of hypoactive dopaminergic neurotransmission
      in RLS, as increased receptor levels can be owing to receptor upregulation in
      response to low levels of endogenous dopamine. The results do not support
      variations in dopamine D2-receptor availability as a correlate to the diurnal
      rhythm of RLS symptoms.

PMID- 16816394
TI  - The effect of epidural sufentanil in ropivacaine on urinary retention in patients
      undergoing gastrectomy.
AB  - BACKGROUND: Although epidural opioids have excellent analgesic property, their
      side-effects limit its use in patient-controlled epidural analgesia (PCEA). This
      study was designed to compare side-effects of epidural sufentanil in ropivacaine
      with that of morphine in ropivacaine focusing on lower urinary tract function
      after major abdominal surgery. METHODS: In total 60 patients undergoing
      gastrectomy were randomly allocated to receive either sufentanil in ropivacaine
      (Group S, n=30) or morphine in ropivacaine (Group M, n=30) for their PCEA.
      Epidural catheter was inserted between the 7th and 8th thoracic spine. Visual
      analogue pain score and side-effects such as nausea, vomiting, pruritus,
      hypotension and urinary retention were evaluated during postoperative days (PODs)
      1 and 2 in the postanaesthetic care unit. RESULTS: The incidence of serious to
      major micturition problem in Group S was lower than that in Group M (P<0.001).
      The incidence of pruritus, nausea and vomiting was also lower in Group S than in
      Group M on POD 1. CONCLUSIONS: The lower incidence of major/serious micturition
      problem in patients receiving sufentanil in ropivacaine thoracic epidural
      analgesia suggests that continuation of urinary drainage may not be necessary
      from POD 1 onwards.

PMID- 16816395
TI  - Sedation during spinal anaesthesia in infants.
AB  - BACKGROUND: Neuraxial anaesthesia in adults decreases the dose of i.v. or
      inhalational anaesthetic needed to reach a desired level of sedation.
      Furthermore, spinal anaesthesia alone has a sedative effect. The mechanism behind
      this phenomenon is presumed to be decreased afferent stimulation of the reticular
      activating system after sympatholysis. We hypothesized that this mechanism is
      equally active in infants undergoing spinal anaesthesia. METHODS: In total, 20
      unpremedicated former preterm infants underwent surgery under spinal anaesthesia
      with hyperbaric bupivacaine 0.5% 1 mg kg(-1) with epinephrine 10 microg kg(-1).
      No additional sedatives or anaesthetics were administered. Sedation was evaluated
      using the bispectral index (BIS) score and the 95% spectral edge frequency
      (SEF(95)). RESULTS: After spinal anaesthesia, mean (SD) BIS began to decrease
      significantly from baseline 97.0 (1.1) to 83.9 (14.4) after 15 min (P=0.006). BIS
      decreased further, reaching the lowest values after 30 min [62.2 (14.0);
      P<0.00001]. Mean (SD) SEF(95) declined from baseline 26.1 (1.8) Hz to 24.3 (3.1)
      after 5 min (P=0.02) and further to 9.9 (3.8) after 30 min (P<0.00001). Mean
      arterial pressure also decreased significantly from 66.5 (4.7) mm Hg within 10
      min to 56.1 (5.6) after spinal anaesthesia (P=0.0002), while heart rate remained
      stable. CONCLUSIONS: These results suggest that sedation after spinal anaesthesia
      in infants is at least as pronounced as in adults. The sedative effect of spinal
      anaesthesia should be kept in mind when additional sedatives are administered,
      especially in former preterm infants.

PMID- 16816396
TI  - Pharmacokinetics and pharmacodynamics of the tetracyclines including
      glycylcyclines.
AB  - The pharmacokinetics of tetracyclines and glycylcyclines are described in three
      groups. Group 1, the oldest group, represented by tetracycline, oxytetracycline,
      chlortetracycline, demeclocycline, lymecycline, methacycline and rolitetracycline
      is characterized by poor absorption after food. Group 2, represented by
      doxycycline and minocycline, is more reliably absorbed orally, while group 3,
      represented by the glycylcycline tigecycline, is injectable only, with an
      improved antibacterial spectrum compared with the tetracyclines. Though
      incompletely understood, the pharmacodynamic properties of the tetracyclines and
      glycylcyclines are summarized.

PMID- 16816397
TI  - European Surveillance of Sexually Transmitted Infections (ESSTI): the first
      combined antimicrobial susceptibility data for Neisseria gonorrhoeae in Western
      Europe.
AB  - OBJECTIVES: To conduct a sentinel surveillance study for antimicrobial resistance
      in Neisseria gonorrhoeae in Western Europe in 2004 as part of the European
      Surveillance of Sexually Transmitted Infections (ESSTI) Programme. METHODS:
      Gonococcal isolates were collected from centres in 12 countries and transferred
      to two reference centres for testing. The same methodology of agar dilution was
      used to determine susceptibility to a range of antimicrobials used for the
      treatment of gonorrhoea including azithromycin, ceftriaxone, ciprofloxacin,
      penicillin and tetracycline. Quality control between the two laboratories was
      assessed during the testing. RESULTS: A total of 1055 gonococcal isolates were
      collected, of which 965 (91.5%) were retrievable for susceptibility testing.
      Resistance was found to be high to ciprofloxacin (30.9%), but also present to
      penicillin (21.3%) and tetracycline (59.8%). Azithromycin resistance was above
      5%, the first time this has been documented in Europe. Three isolates had a low
      level of resistance to ceftriaxone. With regard to quality control between the
      two reference laboratories, 92% of MIC results were within two dilutions.
      CONCLUSIONS: These are the first sentinel surveillance data for Western Europe
      for N. gonorrhoeae and they have implications for choice of antimicrobial for
      treatment of gonorrhoea on a European and a local level. This is the start of the
      formation of a European gonococcal antimicrobial surveillance programme (EURO
      GASP).

PMID- 16816398
TI  - Treatment interruptions in HIV-infected subjects.
AB  - Despite a high antiviral efficacy, the use of highly active antiretroviral
      therapy (HAART) in clinical practice is often impaired by the long-term toxicity
      of antiretroviral treatment, the increased rate of human immunodeficiency virus-1
      (HIV-1) drug resistance in treated patients and the cost of therapies, so that
      possible interruption of HAART has to be considered as part of the current
      clinical practice. However, this strategy is usually followed by a rapid viral
      rebound with a substantial loss of CD4 T lymphocytes because the HIV suppression
      with HAART does not result in reconstitution of the HIV-specific immune response.
      Structured treatment interruption (STI) has already been investigated in HIV
      infected subjects with well-controlled viral replication (initiating treatment
      during primary or chronic HIV infection) and in those with multiple treatment
      failures. A clear benefit of STI in patients with chronic infection remains
      controversial and these benefits are more often observed in patients starting
      treatment during primary HIV infection.

PMID- 16816399
TI  - Characterization of acquired beta-lactamases and their genetic support in
      multidrug-resistant Pseudomonas aeruginosa isolates in Taiwan: the prevalence of
      unusual integrons.
AB  - OBJECTIVES: The present study was conducted to investigate acquired beta
      lactamases and their genetic support in 26 Pseudomonas aeruginosa isolates that
      were resistant to nearly all antipseudomonal drugs from six medical centres in
      Taiwan. METHODS: Acquired beta-lactamases and their genetic support were
      determined by PCR-based strategies. RESULTS: Four and 16 of the 26 isolates were
      found to produce VIM-2 and VIM-3 metallo-beta-lactamases (MBLs), respectively,
      and 1, 1 and 2 isolates produced OXA-17, OXA-10 and PSE-1, respectively. These
      bla genes are all in class 1 integrons that are probably chromosomally located.
      The bla(VIM-3)-containing integron, with a deletion between int1 and the bla(VIM
      3) structural gene, has six gene cassettes, bla(VIM-3), a probable fosfomycin
      resistance determinant, aacA4, aacA4, aadB and aacA4. The bla(VIM-2)-containing
      integron, without detectable 5'-conserved segment, contains four genes cassettes
      (aacA7-bla(VIM-2)-dhfr-aacA5) and is ended by tniC. The bla(OXA-10)-containing
      integron includes a catB3 cassette and a fused gene cassette, which is made up of
      bla(OXA-17) and a novel streptomycin-spectinomycin gene, designated aadA15. The
      bla(OXA-17)-containing integron has three gene cassettes (aacA4-catB2-bla(OXA
      17)) but the 59-base element of the bla(OXA-17) cassette is interrupted by a
      putative transposase gene. The bla(PSE-1)-containing integron has three gene
      cassettes, aacA4, an aadA3-related gene designated aadA3b and bla(PSE-1). PFGE
      revealed genetic diversity among the multidrug-resistant isolates from different
      hospitals. CONCLUSIONS: This study demonstrated the high prevalence of VIM-type
      MBLs and the presence of unusual bla-encoding integrons in multidrug-resistant P.
      aeruginosa isolates in Taiwan. The spread of bla(VIM-2)-related genes by
      horizontal transfer might have occurred.

PMID- 16816400
TI  - High prevalence of OXA-51-type class D beta-lactamases among ceftazidime
      resistant clinical isolates of Acinetobacter spp.: co-existence with OXA-58 in
      multiple centres.
AB  - OBJECTIVES: This study was designed to demonstrate the prevalence of the newly
      discovered carbapenem-hydrolysing class D enzymes, OXA-51-type and OXA-58, among
      clinical isolates of Acinetobacter spp. METHODS: A total of 72 isolates from six
      centres were studied. Isolates were screened by PCR with specific primers for
      bla(OXA-51-type) and bla(OXA-58). PCR products were sequence-analysed. Plasmids
      were digested with EcoRV and genomic DNAs were digested with PvuII. Hybridization
      experiments were done with digoxigenin-labelled specific probes. Macro
      restriction analysis was done on SmaI-digested genomic DNAs. RESULTS: A total of
      56 (77.8%) isolates were positive for bla(OXA-51-type) genes. Sequence analysis
      of the products from 23 selected isolates revealed the occurrence of multiple
      alleles in all contributing centres. The bla(OXA-58) gene was detected among 10
      isolates from five centres. All were also positive for bla(OXA-51-type) genes.
      Among the bla(OXA-58)-positive isolates, two from the same centre were positive
      for a novel OXA-51 allele (OXA-86). Southern hybridization of plasmids and of
      genomic DNAs suggested that bla(OXA-51-type) genes are located on chromosomes
      whereas bla(OXA-58) genes are plasmid borne in these 10 isolates. Plasmid
      profiles and pulsed-field gel electrophoresis patterns indicated the spread of
      the bla(OXA-58) gene among multiple clones. The bla(OXA-51-type) and bla(OXA-58)
      co-carrier strains were mostly associated with a pandrug-resistant phenotype.
      CONCLUSIONS: This study indicated that bla(OXA-58)-bearing plasmids are readily
      spreading among multiple clones of the bla(OXA-51-type)-bearing clinical isolates
      of Acinetobacter spp. Since these isolates are highly resistant to antibiotics
      this finding indicates the existence of a significant problem in Turkish
      hospitals.

PMID- 16816401
TI  - Compact fluorescent lamp phosphors in accidental radiation monitoring.
AB  - The application of lamp phosphors for accidental dosimetry is a new concept.
      Since the materials used in fluorescent lamps are good photo luminescent
      materials, if one can either use the inherent defects present in the phosphor or
      add suitable modifiers to induce thermoluminescence (TL) in these phosphors, then
      the device (fluorescent lamp) can be used as an accidental dosemeter. In
      continuation of our search for a suitable phosphor material, which can serve both
      as an efficient lamp phosphor and as a good radiation monitoring device, detailed
      examination has been carried out on cerium and terbium-doped lanthanum phosphate
      material. A (90)Sr beta source with 50 mCi strength (1.85 GBq) was used as the
      irradiation source for TL studies. The TL response as a function of dose received
      was examined for all phosphors used and it was observed that the intensity of the
      TL peak vs. dose received was a linear function in the dose range 0.1-200 Gy in
      each case. Incidentally LaPO(4): Ce,Tb is a component of the compact fluorescent
      lamp marketed recently as an energy bright light source. Besides having very good
      luminescence efficiency, good dosimetric properties of these phosphors render
      them useful for their use in accidental dosimetry also.

PMID- 16816402
TI  - Agrin elicits membrane lipid condensation at sites of acetylcholine receptor
      clusters in C2C12 myotubes.
AB  - The formation of the neuromuscular junction is characterized by the progressive
      accumulation of nicotinic acetylcholine receptors (AChRs) in the postsynaptic
      membrane facing the nerve terminal, induced predominantly through the
      agrin/muscle-specific kinase (MuSK) signaling cascade. However, the cellular
      mechanisms linking MuSK activation to AChR clustering are still poorly
      understood. Here, we investigate whether lipid rafts are involved in agrin
      elicited AChR clustering in a mouse C2C12 cell line. We observed that in C2C12
      myotubes, both AChR clustering and cluster stability were dependent on
      cholesterol, because depletion by methyl-beta-cyclodextrin inhibited cluster
      formation or dispersed established clusters. Importantly, AChR clusters resided
      in ordered membrane domains, a biophysical property of rafts, as probed by
      Laurdan two-photon fluorescence microscopy. We isolated detergent-resistant
      membranes (DRMs) by three different biochemical procedures, all of which generate
      membranes with similar cholesterol/GM1 ganglioside contents, and these were
      enriched in several postsynaptic components, notably AChR, syntrophin, and raft
      markers flotillin-2 and caveolin-3. Agrin did not recruit AChRs into DRMs,
      suggesting that they are present in rafts independently of agrin activation.
      Consequently, in C2C12 myotubes, agrin likely triggers AChR clustering or
      maintains clusters through the coalescence of lipid rafts. These data led us to
      propose a model in which lipid rafts play a pivotal role in the assembly of the
      postsynaptic membrane at the neuromuscular junction upon agrin signaling.

PMID- 16816403
TI  - AKT-independent phosphorylation of TSC2 and activation of mTOR and ribosomal
      protein S6 kinase signaling by prostaglandin F2alpha.
AB  - Prostaglandin F2alpha (PGF2alpha) is an important mediator of corpus luteum (CL)
      regression, although the cellular signaling events that mediate this process have
      not been clearly identified. It is established that PGF2alpha binds to a G
      proteincoupled receptor (GPCR) to stimulate protein kinase C (PKC) and Raf-MEK
      Erk signaling in luteal cells. The present experiments were performed to
      determine whether PGF2alpha stimulates the mammalian target of rapamycin
      (mTOR)/ribosomal protein S6 kinase 1 (S6K1) signaling pathway in steroidogenic
      luteal cells. We demonstrate that PGF2alpha treatment results in a timeand
      concentration-dependent stimulation of the phosphorylation and activation of
      S6K1. The stimulation of S6K1 in response to PGF2alpha treatment was abolished by
      the mTOR inhibitor rapamycin. Treatment with PGF2alpha did not increase AKT
      phosphorylation but increased the phosphorylation of Erk and the tumor suppressor
      protein tuberous sclerosis complex 2 (TSC2), an upstream regulator of mTOR. The
      effects of PGF2alpha were mimicked by the PKC activator PMA and inhibited by
      U0126, a MEK1 inhibitor. The activation of mTOR/S6K1 and putative down stream
      processes involving the translational apparatus (i.e. 4EBP1 phosphorylation,
      release of 4EBP1 binding in m(7)G cap binding assays, and the phosphorylation and
      synthesis of S6) were completely sensitive to treatment with rapamycin,
      implicating mTOR in the actions of PGF2alpha. Taken together, our data suggest
      that GPCR activation in response to PGF2alpha stimulates the mTOR pathway which
      increases the translational machinery in luteal cells. The translation of
      proteins under the control of mTOR may have implications for luteal development
      and regression and offer new strategies for therapeutic intervention in PGF2alpha
      target tissues.

PMID- 16816404
TI  - 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated
      protein kinase phosphorylation inhibits basal and insulin-stimulated glucose
      uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes.
AB  - The objective of this study was to investigate the effects of 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR)-induced AMP-activated protein kinase
      (AMPK) activation on basal and insulin-stimulated glucose and fatty acid
      metabolism in isolated rat adipocytes. AICAR-induced AMPK activation profoundly
      inhibited basal and insulin-stimulated glucose uptake, lipogenesis, glucose
      oxidation, and lactate production in fat cells. We also describe the novel
      findings that AICAR-induced AMPK phosphorylation significantly reduced palmitate
      (32%) and oleate uptake (41%), which was followed by a 50% reduction in palmitate
      oxidation despite a marked increase in AMPK and acetyl-CoA carboxylase
      phosphorylation. Compound C, a selective inhibitor of AMPK, not only completely
      prevented the inhibitory effect of AICAR on palmitate oxidation but actually
      caused a 2.2-fold increase in this variable. Compound C also significantly
      increased palmitate oxidation in the presence of inhibitory concentrations of
      malonyl-CoA and etomoxir indicating an increase in CPT1 activity. In contrast to
      skeletal muscle in which AMPK stimulates fatty acid oxidation to provide ATP as a
      fuel, we propose that AMPK activation inhibits lipogenesis and fatty acid
      oxidation in adipocytes. Inhibition of lipogenesis would conserve ATP under
      conditions of cellular stress, although suppression of intra-adipocyte oxidation
      would spare fatty acids for exportation to other tissues where their utilization
      is crucial for energy production. Additionally, the stimulatory effect of
      compound C on long chain fatty acid oxidation provides a novel pharmacological
      approach to promote energy dissipation in adipocytes, which may be of therapeutic
      importance for obesity and type II diabetes.

PMID- 16816405
TI  - Nucleosome depletion activates poised RNA polymerase III at unconventional
      transcription sites in Saccharomyces cerevisiae.
AB  - RNA polymerase (pol) III, assisted by the transcription factors TFIIIC and
      TFIIIB, transcribes small untranslated RNAs, such as tRNAs. In addition to known
      pol III-transcribed genes, the Saccharomyces cerevisiae genome contains loci
      (ZOD1, ETC1-8) associated to incomplete pol III transcription complexes
      (Moqtaderi, Z., and Struhl, K. (2004) Mol. Cell. Biol. 24, 4118-4127). We show
      that a short segment of the ZOD1 locus, containing box A and box B promoter
      elements and a termination signal between them, directs the pol III-dependent
      production of a small RNA both in vitro and in vivo. In yeast cells, the levels
      of both ZOD1- and ETC5-specific transcripts were dramatically enhanced upon
      nucleosome depletion. Remarkably, transcription factor and pol III occupancy at
      the corresponding loci did not change significantly upon derepression, thus
      suggesting that chromatin opening activates poised pol III to transcription.
      Comparative genomic analysis revealed that the ZOD1 promoter is the only
      surviving portion of a tDNA(Ile) ancestor, whose transcription capacity has been
      preserved throughout evolution independently from the encoded RNA product.
      Similarly, another TFIIIC/TFIIIB-associated locus, close to the YGR033c open
      reading frame, was found to be the strictly conserved remnant of an ancient
      tDNA(Arg). The maintenance, by eukaryotic genomes, of chromatin-repressed, non
      coding transcription units has implications for both genome expression and
      organization.

PMID- 16816406
TI  - Evidence that L-glutamate can act as an exogenous signal to modulate root growth
      and branching in Arabidopsis thaliana.
AB  - The roots of many plant species are known to use inorganic nitrogen, in the form
      of , as a cue to initiate localized root proliferation within nutrient-rich
      patches of soil. We report here that, at micromolar concentrations and in a
      genotype-dependent manner, exogenous l-glutamate is also able to elicit complex
      changes in Arabidopsis root development. l-Glutamate is perceived specifically at
      the primary root tip and inhibits mitotic activity in the root apical meristem,
      but does not interfere with lateral root initiation or outgrowth. Only some time
      after emergence do lateral roots acquire l-glutamate sensitivity, indicating that
      their ability to respond to l-glutamate is developmentally regulated. Comparisons
      between different Arabidopsis ecotypes revealed a remarkable degree of natural
      variation in l-glutamate sensitivity, with C24 being the most sensitive. The aux1
      7 auxin transport mutant had reduced l-glutamate sensitivity, suggesting a
      possible interaction between l-glutamate and auxin signaling. Surprisingly, two
      loss-of-function mutants at the AXR1 locus (axr1-3 and axr1-12) were
      hypersensitive to l-glutamate. A pharmacological approach, using agonists and
      antagonists of mammalian ionotropic glutamate receptors, was unable to provide
      evidence of a role for their plant homologs in sensing exogenous glutamate. We
      discuss the mechanism of l-glutamate sensing and the possible ecological
      significance of the observed l-glutamate-elicited changes in root architecture.

PMID- 16816408
TI  - Effects of internal conductance on the temperature dependence of the
      photosynthetic rate in spinach leaves from contrasting growth temperatures.
AB  - The photosynthetic rate may be strongly limited by internal conductance from the
      intercellular airspace to the chloroplast stroma (g(i)). However, the effects of
      growth and leaf temperature on g(i) are still unclarified. In this work, we
      determined the temperature dependence of g(i) in spinach leaves grown at 30/25
      degrees C (high temperature; HT) and 15/10 degrees C (low temperature; LT), using
      the concurrent measurements of the gas exchange rate and stable carbon isotope
      ratio. Moreover, we quantified the effects of g(i) on the temperature dependence
      of the photosynthetic rate. We measured g(i) and the photosynthetic rate at a
      CO(2) concentration of 360 microl l(-1) under saturating light (A(360)) at
      different leaf temperatures. The optimum temperature for A(360) was 28.5 degrees
      C in HT leaves and 22.9 degrees C in LT leaves. The optimum temperatures for g(i)
      were almost similar to those of A(360) in both HT and LT leaves. There was a
      strong linear relationship between A(360) and g(i). The photosynthetic rates
      predicted from the C(3) photosynthesis model taking account of g(i) agreed well
      with A(360) in both HT and LT leaves. The temperature coefficients (Q(10)) of
      g(i) between 10 and 20 degrees C were 2.0 and 1.8 in HT and LT leaves,
      respectively. This suggests that g(i) was determined not only by physical
      diffusion but by processes facilitated by protein(s). The limitation of the
      photosynthetic rate imposed by g(i) increased with leaf temperature and was
      greater than the limitation of the stomatal conductance at any temperature, in
      both HT and LT leaves. This study suggests that g(i) substantially limits the
      photosynthetic rate, especially at higher temperatures.

PMID- 16816407
TI  - Regulatory mechanisms of ROI generation are affected by rice spl mutations.
AB  - Reactive oxygen intermediates (ROIs) play a pivotal role in the hypersensitive
      response (HR) in disease resistance. NADPH oxidase is a major source of ROI;
      however, the mechanisms of its regulation are unclear. Rice spl mutants
      spontaneously form lesions which resemble those occurring during the HR,
      suggesting that the mutations affect regulation of the HR. We found that spl2,
      spl7 and spl11 mutant cells accumulated increased amounts of H(2)O(2) in response
      to rice blast fungal elicitor. Increased accumulation of ROIs was suppressed by
      inhibition of NADPH oxidase in the spl cells, and was also observed in the ozone
      exposed spl plants. These mutants have sufficient activities of ROI-scavenging
      enzymes compared with the wild type. In addition, spl7 mutant cells accumulated
      higher amounts of H(2)O(2) when treated with calyculin A (CA), an inhibitor of
      protein phosphatase. Furthermore, spl2 mutant plants exhibited accelerated
      accumulation of H(2)O(2) and increased rates of cell death in response to
      wounding. These results suggest that the spl2, spl7 and spl11 mutants are
      defective in the regulation of NADPH oxidase, and the spl7 mutation may give rise
      to enhancement of the signaling pathway which protein dephosphorylation controls,
      while the spl2 mutation affects both the pathogen-induced and wound-induced
      signaling pathways.

PMID- 16816409
TI  - Isolation and characterization of high temperature-resistant germination mutants
      of Arabidopsis thaliana.
AB  - Temperature is a primary environmental cue for seed germination of many weeds and
      vegetables. To investigate the mechanism of germination regulation by
      temperature, we selected five high temperature (thermoinhibition)-resistant
      germination mutants (TRW lines) from 20,000 T-DNA insertion lines of Arabidopsis.
      Segregation analyses indicated that each of the five lines had single locus
      recessive mutations. The seeds of TRW134-15 and TRW187 showed reduced sensitivity
      to ABA and also to the gibberrellin biosynthesis inhibitor, paclobutrazol.
      Genetic and nucleotide sequencing analyses indicated that TRW187 is a new allele
      of abi3 (abi3-14). TRW71-1 exhibited a maternal effect for both thermoinhibition
      resistant and transparent testa phenotypes, and genetic analysis revealed that
      the mutation was allelic to tt7 (tt7-4 sib). Interestingly, the seeds of reduced
      dormancy mutants rdo1, rdo2, rdo3 and rdo4 were also thermoinhibition tolerant,
      and all the TRW seeds showed reduced dormancy. Like rdo3, TRW13-1 had shorter
      siliques and slightly shorter stems than the wild type. The mutation of TRW13-1
      was mapped to the bottom arm of chromosome 1 where rdo3 has also been mapped, but
      the two mutants are not allelic. We designated TRW13-1 as thermoinhibition
      resistant germination 1 (trg1). We also mapped the ABA-insensitive mutation of
      TRW134-15 to the bottom arm of chromosome 5 and named it trg2. These results show
      that both embryo/endosperm and maternal factors contribute to germination
      inhibition at supraoptimal temperatures in Arabidopsis. In addition, we confirm
      the role of ABA in thermoinhibition of seed germination and a link between seed
      physiological dormancy and response to high temperature.

PMID- 16816410
TI  - Expression of a WIPK-activated transcription factor results in increase of
      endogenous salicylic acid and pathogen resistance in tobacco plants.
AB  - NtWIF is a transcription factor activated upon phosphorylation by wound-induced
      protein kinase (WIPK) in tobacco plants. Transgenic tobacco plants overexpressing
      NtWIF exhibited constitutive accumulation of transcripts for pathogenesis-related
      genes, PR-1a and PR-2. Salicylic acid levels were 50-fold higher than those in
      wild-type plants. The levels of jasmonic acid and IAA did not significantly
      differ, while an increase of ABA upon wounding was delayed by 3 h in the
      transgenics. When challenged with tobacco mosaic virus, lesions developed faster
      and were smaller in the transgenic plants. The results suggest that NtWIF is
      likely to influence salicylic acid biosynthesis, being located downstream of
      WIPK.

PMID- 16816411
TI  - RNAi knock-down of ENOD40s leads to significant suppression of nodule formation
      in Lotus japonicus.
AB  - ENOD40 is one of the most intriguing early nodulin genes that is known to be
      induced very early in response to interaction of legume plants with symbiotic
      Rhizobium bacteria, but its function in the nodulation process is still not
      known. Lotus japonicus has two ENOD40 genes: LjENOD40-1 is abundantly induced in
      very early stages of bacterial infection or Nod factor application, whereas
      LjENOD40-2 is abundantly expressed only in mature nodules. We generated
      transgenic lines of L. japonicus with an RNAi (RNA interference) construct that
      expresses hairpin double-stranded RNA for LjENOD40-1 to induce sequence-specific
      RNA silencing. In the transgenic plants, expression of both LjENOD40-1 and -2 was
      significantly reduced, and no accumulation of ENOD40 transcripts was detected
      upon Mesorhizobium loti inoculation. The transgenic plants exhibited very poor
      nodulation (only 0-2 nodules per plant) and could not grow well without
      additional nitrogen supply. Analysis of segregation in the T(2) progeny indicated
      that the suppression of nodulation is perfectly linked with the presence of the
      transgene. Microscopic observation of the infection process using lacZ-labeled M.
      loti, together with expression analysis of infection-related nodulin genes,
      demonstrated that ENOD40 knock-down did not inhibit the initiation of the
      bacterial infection process. In contrast, nodule primordium initiation and
      subsequent nodule development were significantly suppressed in the transgenic
      plants. These results clearly indicate that ENOD40 is required for nodule
      initiation and subsequent organogenesis, but is not involved in early infection
      events.

PMID- 16816412
TI  - Melanotic mutants in Drosophila: pathways and phenotypes.
AB  - Mutations in >30 genes that regulate different pathways and developmental
      processes are reported to cause a melanotic phenotype in larvae. The observed
      melanotic masses were generally linked to the hemocyte-mediated immune response.
      To investigate whether all black masses are associated with the cellular immune
      response, we characterized melanotic masses from mutants in 14 genes. We found
      that the melanotic masses can be subdivided into melanotic nodules engaging the
      hemocyte-mediated encapsulation and into melanizations that are not encapsulated
      by hemocytes. With rare exception, the encapsulation is carried out by
      lamellocytes. Encapsulated nodules are found in the hemocoel or in association
      with the lymph gland, while melanizations are located in the gut, salivary gland,
      and tracheae. In cactus mutants we found an additional kind of melanized mass
      containing various tissues. The development of these tissue agglomerates is
      dependent on the function of the dorsal gene. Our results show that the phenotype
      of each mutant not only reflects its connection to a particular genetic pathway
      but also points to the tissue-specific role of the individual gene.

PMID- 16816413
TI  - Ubiquitin-like protein 5 positively regulates chaperone gene expression in the
      mitochondrial unfolded protein response.
AB  - Perturbation of the protein-folding environment in the mitochondrial matrix
      selectively upregulates the expression of nuclear genes encoding mitochondrial
      chaperones. To identify components of the signal transduction pathway(s)
      mediating this mitochondrial unfolded protein response (UPR(mt)), we first
      isolated a temperature-sensitive mutation (zc32) that conditionally activates the
      UPR(mt) in C. elegans and subsequently searched for suppressors by systematic
      inactivation of genes. RNAi of ubl-5, a gene encoding a ubiquitin-like protein,
      suppresses activation of the UPR(mt) markers hsp-60::gfp and hsp-6::gfp by the
      zc32 mutation and by other manipulations that promote mitochondrial protein
      misfolding. ubl-5 (RNAi) inhibits the induction of endogenous mitochondrial
      chaperone encoding genes hsp-60 and hsp-6 and compromises the ability of animals
      to cope with mitochondrial stress. Mitochondrial morphology and assembly of multi
      subunit mitochondrial complexes of biotinylated proteins are also perturbed in
      ubl-5(RNAi) worms, indicating that UBL-5 also counteracts physiological levels of
      mitochondrial stress. Induction of mitochondrial stress promotes accumulation of
      GFP-tagged UBL-5 in nuclei of transgenic worms, suggesting that UBL-5 effects a
      nuclear step required for mounting a response to the threat of mitochondrial
      protein misfolding.

PMID- 16816414
TI  - Molecular characterization of teflon, a gene required for meiotic autosome
      segregation in male Drosophila melanogaster.
AB  - Drosophila melanogaster males lack recombination and have evolved a mechanism of
      meiotic chromosome segregation that is independent of both the chiasmatic and
      achiasmatic segregation systems of females. The teflon (tef) gene is specifically
      required in males for proper segregation of autosomes and provides a genetic tool
      for understanding recombination-independent mechanisms of pairing and segregation
      as well as differences in sex chromosome vs. autosome segregation. Here we report
      on the cloning of the tef gene and the molecular characterization of tef
      mutations. Rescue experiments using a GAL4-driven pUAS transgene demonstrate that
      tef corresponds to predicted Berkeley Drosophila Genome Project (BDGP) gene
      CG8961 and that tef expression is required in the male germ line prior to
      spermatocyte stage S4. Consistent with this early prophase requirement,
      expression of tef was found to be independent of regulators of meiotic M phase
      initiation or progression. The predicted Tef protein contains three C2H2 zinc
      finger motifs, one at the amino terminus and two in tandem at the carboxyl
      terminus. In addition to the zinc-finger motifs, a 44- to 45-bp repeat is
      conserved in three related Drosophila species. On the basis of these findings, we
      propose a role for Tef as a bridging molecule that holds autosome bivalents
      together via heterochromatic connections.

PMID- 16816415
TI  - The mechanism of secondary nondisjunction in Drosophila melanogaster females.
AB  - Bridges (1916) observed that X chromosome nondisjunction was much more frequent
      in XXY females than it was in genetically normal XX females. In addition,
      virtually all cases of X nondisjunction in XXY females were due to XX <--> Y
      segregational events in oocytes in which the two X chromosomes had failed to
      undergo crossing over. He referred to these XX <--> Y segregation events as
      "secondary nondisjunction." Cooper (1948) proposed that secondary nondisjunction
      results from the formation of an X-Y-X trivalent, such that the Y chromosome
      directs the segregation of two achiasmate X chromosomes to opposite poles on the
      first meiotic spindle. Using in situ hybridization to X and YL chromosomal
      satellite sequences, we demonstrate that XX <--> Y segregations are indeed
      presaged by physical associations of the X and Y chromosomal heterochromatin. The
      physical colocalization of the three sex chromosomes is observed in virtually all
      oocytes in early prophase and maintained at high frequency until midprophase in
      all genotypes examined. Although these XXY associations are usually dissolved by
      late prophase in oocytes that undergo X chromosomal crossing over, they are
      maintained throughout prophase in oocytes with nonexchange X chromosomes. The
      persistence of such XXY associations in the absence of exchange presumably
      facilitates the segregation of the two X chromosomes and the Y chromosome to
      opposite poles on the developing meiotic spindle. Moreover, the observation that
      XXY pairings are dissolved at the end of pachytene in oocytes that do undergo X
      chromosomal crossing over demonstrates that exchanges can alter heterochromatic
      (and thus presumably centromeric) associations during meiotic prophase.

PMID- 16816416
TI  - Antagonism of Chk1 signaling in the G2 DNA damage checkpoint by dominant alleles
      of Cdr1.
AB  - Activation of the Chk1 protein kinase by DNA damage enforces a checkpoint that
      maintains Cdc2 in its inactive, tyrosine-15 (Y15) phosphorylated state. Chk1
      downregulates the Cdc25 phosphatases and concomitantly upregulates the Wee1
      kinases that control the phosphorylation of Cdc2. Overproduction of Chk1 causes
      G(2) arrest/delay independently of DNA damage and upstream checkpoint genes. We
      utilized this to screen fission yeast for mutations that alter sensitivity to
      Chk1 signaling. We describe three dominant-negative alleles of cdr1, which render
      cells supersensitive to Chk1 levels, and suppress the checkpoint defects of
      chk1Delta cells. Cdr1 encodes a protein kinase previously identified as a
      negative regulator of Wee1 activity in response to limited nutrition, but Cdr1
      has not previously been linked to checkpoint signaling. Overproduction of Cdr1
      promotes checkpoint defects and exacerbates the defective response to DNA damage
      of cells lacking Chk1. We conclude that regulation of Wee1 by Cdr1 and possibly
      by related kinases is an important antagonist of Chk1 signaling and represents a
      novel negative regulation of cell cycle arrest promoted by this checkpoint.

PMID- 16816417
TI  - Genomewide evolutionary rates in laboratory and wild yeast.
AB  - As wild organisms adapt to the laboratory environment, they become less relevant
      as biological models. It has been suggested that a commonly used S. cerevisiae
      strain has rapidly accumulated mutations in the lab. We report a low-to
      intermediate rate of protein evolution in this strain relative to wild isolates.

PMID- 16816418
TI  - Genetic exchange between homeologous sequences in mammalian chromosomes is
      averted by local homology requirements for initiation and resolution of
      recombination.
AB  - We examined the mechanism by which recombination between imperfectly matched
      sequences (homeologous recombination) is suppressed in mammalian chromosomes. DNA
      substrates were constructed, each containing a thymidine kinase (tk) gene
      disrupted by insertion of an XhoI linker and referred to as a "recipient" gene.
      Each substrate also contained one of several "donor" tk sequences that could
      potentially correct the recipient gene via recombination. Each donor sequence
      either was perfectly homologous to the recipient gene or contained homeologous
      sequence sharing only 80% identity with the recipient gene. Mouse Ltk(-)
      fibroblasts were stably transfected with the various substrates and tk(+)
      segregants produced via intrachromosomal recombination were recovered. We
      observed exclusion of homeologous sequence from gene conversion tracts when
      homeologous sequence was positioned adjacent to homologous sequence in the donor
      but not when homeologous sequence was surrounded by homology in the donor. Our
      results support a model in which homeologous recombination in mammalian
      chromosomes is suppressed by a nondestructive dismantling of mismatched
      heteroduplex DNA (hDNA) intermediates. We suggest that mammalian cells do not
      dismantle mismatched hDNA by responding to mismatches in hDNA per se but rather
      rejection of mismatched hDNA appears to be driven by a requirement for localized
      homology for resolution of recombination.

PMID- 16816419
TI  - A genomewide screen for suppressors of par-2 uncovers potential regulators of PAR
      protein-dependent cell polarity in Caenorhabditis elegans.
AB  - The PAR proteins play an essential role in establishing and maintaining cell
      polarity. While their function is conserved across species, little is known about
      their regulators and effectors. Here we report the identification of 13 potential
      components of the C. elegans PAR polarity pathway, identified in an RNAi-based,
      systematic screen to find suppressors of par-2(it5ts) lethality. Most of these
      genes are conserved in other species. Phenotypic analysis of double-mutant
      animals revealed that some of the suppressors can suppress lethality associated
      with the strong loss-of-function allele par-2(lw32), indicating that they might
      impinge on the PAR pathway independently of the PAR-2 protein. One of these is
      the gene nos-3, which encodes a homolog of Drosophila Nanos. We find that nos-3
      suppresses most of the phenotypes associated with loss of par-2 function,
      including early cell division defects and maternal-effect sterility. Strikingly,
      while PAR-1 activity was essential in nos-3; par-2 double mutants, its asymmetric
      localization at the posterior cortex was not restored, suggesting that the
      function of PAR-1 is independent of its cortical localization. Taken together,
      our results identify conserved components that regulate PAR protein function and
      also suggest a role for NOS-3 in PAR protein-dependent cell polarity.

PMID- 16816420
TI  - Nonlinear tests for genomewide association studies.
AB  - As millions of single-nucleotide polymorphisms (SNPs) have been identified and
      high-throughput genotyping technologies have been rapidly developed, large-scale
      genomewide association studies are soon within reach. However, since a genomewide
      association study involves a large number of SNPs it is therefore nearly
      impossible to ensure a genomewide significance level of 0.05 using the available
      statistics, although the multiple-test problems can be alleviated, but not
      sufficiently, by the use of tagging SNPs. One strategy to circumvent the multiple
      test problem associated with genome-wide association tests is to develop novel
      test statistics with high power. In this report, we introduce several nonlinear
      tests, which are based on nonlinear transformation of allele or haplotype
      frequencies. We investigate the power of the nonlinear test statistics and
      demonstrate that under certain conditions, some nonlinear test statistics have
      much higher power than the standard chi2-test statistic. Type I error rates of
      the nonlinear tests are validated using simulation studies. We also show that a
      class of similarity measure-based test statistics is based on the quadratic
      function of allele or haplotype frequencies, and thus they belong to nonlinear
      tests. To evaluate their performance, the nonlinear test statistics are also
      applied to three real data sets. Our study shows that nonlinear test statistics
      have great potential in association studies of complex diseases.

PMID- 16816421
TI  - A first-generation metric linkage disequilibrium map of bovine chromosome 6.
AB  - We constructed a metric linkage disequilibrium (LD) map of bovine chromosome 6
      (BTA6) on the basis of data from 220 SNPs genotyped on 433 Australian dairy
      bulls. This metric LD map has distances in LD units (LDUs) that are analogous to
      centimorgans in linkage maps. The LD map of BTA6 has a total length of 8.9 LDUs.
      Within the LD map, regions of high LD (represented as blocks) and regions of low
      LD (steps) are observed, when plotted against the integrated map in kilobases. At
      the most stringent block definition, namely a set of loci with zero LDU increase
      over the span of these markers, BTA6 comprises 40 blocks, accounting for 41% of
      the chromosome. At a slightly lower stringency of block definition (a set of loci
      covering a maximum of 0.2 LDUs on the LD map), up to 81% of BTA6 is spanned by 46
      blocks and with 13 steps that are likely to reflect recombination hot spots. The
      mean swept radius (the distance over which LD is likely to be useful for mapping)
      is 13.3 Mb, confirming extensive LD in Holstein-Friesian dairy cattle, which
      makes such populations ideal for whole-genome association studies.

PMID- 16816422
TI  - Novel role for checkpoint Rad53 protein kinase in the initiation of chromosomal
      DNA replication in Saccharomyces cerevisiae.
AB  - A novel role for Rad53 in the initiation of DNA replication that is independent
      of checkpoint or deoxynucleotide regulation is proposed. Rad53 kinase is part of
      a signal transduction pathway involved in the DNA damage and replication
      checkpoints, while Cdc7-Dbf4 kinase (DDK) is important for the initiation of DNA
      replication. In addition to the known cdc7-rad53 synthetic lethality, rad53
      mutations suppress mcm5-bob1, a mutation in the replicative MCM helicase that
      bypasses DDK's essential role. Rad53 kinase activity but neither checkpoint FHA
      domain is required. Conversely, Rad53 kinase can be activated without DDK.
      Rad53's role in replication is independent of both DNA and mitotic checkpoints
      because mutations in other checkpoint genes that act upstream or downstream of
      RAD53 or in the mitotic checkpoint do not exhibit these phenotypes. Because Rad53
      binds an origin of replication mainly through its kinase domain and rad53 null
      mutants display a minichromosome loss phenotype, Rad53 is important in the
      initiation of DNA replication, as are DDK and Mcm2-7 proteins. This unique
      requirement for Rad53 can be suppressed by the deletion of the major histone
      H3/H4 gene pair, indicating that Rad53 may be regulating initiation by
      controlling histone protein levels and/or by affecting origin chromatin
      structure.

PMID- 16816424
TI  - Accumulation of recessive lethal mutations in Saccharomyces cerevisiae mlh1
      mismatch repair mutants is not associated with gross chromosomal rearrangements.
AB  - We examined mismatch repair (MMR)-defective diploid strains of budding yeast
      grown for approximately 160 generations to determine whether decreases in spore
      viability due to the uncovering of recessive lethal mutations correlated with an
      increase in gross chromosomal rearrangements (GCRs). No GCRs were detected
      despite dramatic decreases in spore viability, suggesting that frameshift and/or
      other unrepaired DNA replication lesions play a greater role than chromosomal
      instability in decreasing viability in MMR-defective strains.

PMID- 16816423
TI  - Drosophila Reptin and other TIP60 complex components promote generation of silent
      chromatin.
AB  - Histone acetyltransferase (HAT) complexes have been linked to activation of
      transcription. Reptin is a subunit of different chromatin-remodeling complexes,
      including the TIP60 HAT complex. In Drosophila, Reptin also copurifies with the
      Polycomb group (PcG) complex PRC1, which maintains genes in a transcriptionally
      silent state. We demonstrate genetic interactions between reptin mutant flies and
      PcG mutants, resulting in misexpression of the homeotic gene Scr. Genetic
      interactions are not restricted to PRC1 components, but are also observed with
      another PcG gene. In reptin homozygous mutant cells, a Polycomb response-element
      linked reporter gene is derepressed, whereas endogenous homeotic gene expression
      is not. Furthermore, reptin mutants suppress position-effect variegation (PEV), a
      phenomenon resulting from spreading of heterochromatin. These features are shared
      with three other components of TIP60 complexes, namely Enhancer of Polycomb,
      Domino, and dMRG15. We conclude that Drosophila Reptin participates in epigenetic
      processes leading to a repressive chromatin state as part of the fly TIP60 HAT
      complex rather than through the PRC1 complex. This shows that the TIP60 complex
      can promote the generation of silent chromatin.

PMID- 16816425
TI  - Introns regulate RNA and protein abundance in yeast.
AB  - The purpose of introns in the architecturally simple genome of Saccharomyces
      cerevisiae is not well understood. To assay the functional relevance of introns,
      a series of computational analyses and several detailed deletion studies were
      completed on the intronic genes of S. cerevisiae. Mining existing data from
      genomewide studies on yeast revealed that intron-containing genes produce more
      RNA and more protein and are more likely to be haplo-insufficient than
      nonintronic genes. These observations for all intronic genes held true for
      distinct subsets of genes including ribosomal, nonribosomal, duplicated, and
      nonduplicated. Corroborating the result of computational analyses, deletion of
      introns from three essential genes decreased cellular RNA levels and caused
      measurable growth defects. These data provide evidence that introns improve
      transcriptional and translational yield and are required for competitive growth
      of yeast.

PMID- 16816426
TI  - The conserved ATPase Get3/Arr4 modulates the activity of membrane-associated
      proteins in Saccharomyces cerevisiae.
AB  - The regulation of cellular membrane dynamics is crucial for maintaining proper
      cell growth and division. The Cdc48-Npl4-Ufd1 complex is required for several
      regulated membrane-associated processes as part of the ubiquitin-proteasome
      system, including ER-associated degradation and the control of lipid composition
      in yeast. In this study we report the results of a genetic screen in
      Saccharomyces cerevisiae for extragenic suppressors of a temperature-sensitive
      npl4 allele and the subsequent analysis of one suppressor, GET3/ARR4. The GET3
      gene encodes an ATPase with homology to the regulatory component of the bacterial
      arsenic pump. Mutants of GET3 rescue several phenotypes of the npl4 mutant and
      transcription of GET3 is coregulated with the proteasome, illustrating a
      functional relationship between GET3 and NPL4 in the ubiquitin-proteasome system.
      We have further found that Get3 biochemically interacts with the trans-membrane
      domain proteins Get1/Mdm39 and Get2/Rmd7 and that Deltaget3 is able to suppress
      phenotypes of get1 and get2 mutants, including sporulation defects. In
      combination, our characterization of GET3 genetic and biochemical interactions
      with NPL4, GET1, and GET2 implicates Get3 in multiple membrane-dependent
      pathways.

PMID- 16816427
TI  - Four novel suppressors of gic1 gic2 and their roles in cytokinesis and polarized
      cell growth in Saccharomyces cerevisiae.
AB  - Gic1 and Gic2 are two Cdc42/Rac interactive binding (CRIB) domain-containing
      effectors of Cdc42-GTPase that promote polarized cell growth in S. cerevisiae. To
      identify novel genes that functionally interact with Gic1 and Gic2, we screened
      for high-copy suppressors of a gic1 gic2 temperature-sensitive strain. We
      identified two pairs of structurally related genes, SKG6-TOS2 and VHS2-MLF3.
      These genes have been implicated in polarized cell growth, but their functions
      have not previously been characterized. We found that overproduction of Skg6 and
      Tos2 in wild-type cells causes aberrant localization of Cdc3 septin and actin
      structures as well as defective recruitment of Hof1 and impaired formation of the
      septum at the mother-bud neck. These data suggest a negative regulatory function
      for Skg6 and Tos2 in cytokinesis. Consistent with this model, deletion of SKG6
      suppresses the growth defects associated with loss of HOF1, a positive regulator
      of cytokinesis. Our analysis of the second pair of gic1 gic2 suppressors, VHS2
      and MLF3, suggests that they regulate polarization of the actin cytoskeleton and
      cell growth and function in a pathway distinct from and parallel to GIC1 and
      GIC2.

PMID- 16816428
TI  - No accelerated rate of protein evolution in male-biased Drosophila pseudoobscura
      genes.
AB  - Sexually dimorphic traits are often subject to diversifying selection. Genes with
      a male-biased gene expression also are probably affected by sexual selection and
      have a high rate of protein evolution. We used SAGE to measure sex-biased gene
      expression in Drosophila pseudoobscura. Consistent with previous results from D.
      melanogaster, a larger number of genes were male biased (402 genes) than female
      biased (138 genes). About 34% of the genes changed the sex-related expression
      pattern between D. melanogaster and D. pseudoobscura. Combining gene expression
      with protein divergence between both species, we observed a striking difference
      in the rate of evolution for genes with a male-biased gene expression in one
      species only. Contrary to expectations, D. pseudoobscura genes in this category
      showed no accelerated rate of protein evolution, while D. melanogaster genes did.
      If sexual selection is driving molecular evolution of male-biased genes, our data
      imply a radically different selection regime in D. pseudoobscura.

PMID- 16816429
TI  - Reconstructing the evolutionary history of paralogous APETALA1/FRUITFULL-like
      genes in grasses (Poaceae).
AB  - Gene duplication is an important mechanism for the generation of evolutionary
      novelty. Paralogous genes that are not silenced may evolve new functions
      (neofunctionalization) that will alter the developmental outcome of preexisting
      genetic pathways, partition ancestral functions (subfunctionalization) into
      divergent developmental modules, or function redundantly. Functional divergence
      can occur by changes in the spatio-temporal patterns of gene expression and/or by
      changes in the activities of their protein products. We reconstructed the
      evolutionary history of two paralogous monocot MADS-box transcription factors,
      FUL1 and FUL2, and determined the evolution of sequence and gene expression in
      grass AP1/FUL-like genes. Monocot AP1/FUL-like genes duplicated at the base of
      Poaceae and codon substitutions occurred under relaxed selection mostly along the
      branch leading to FUL2. Following the duplication, FUL1 was apparently lost from
      early diverging taxa, a pattern consistent with major changes in grass floral
      morphology. Overlapping gene expression patterns in leaves and spikelets indicate
      that FUL1 and FUL2 probably share some redundant functions, but that FUL2 may
      have become temporally restricted under partial subfunctionalization to
      particular stages of floret development. These data have allowed us to
      reconstruct the history of AP1/FUL-like genes in Poaceae and to hypothesize a
      role for this gene duplication in the evolution of the grass spikelet.

PMID- 16816430
TI  - Gene conversion between direct noncoding repeats promotes genetic and phenotypic
      diversity at a regulatory locus of Zea mays (L.).
AB  - While evolution of coding sequences has been intensively studied, diversification
      of noncoding regulatory regions remains poorly understood. In this study, we
      investigated the molecular evolution of an enhancer region located 5 kb upstream
      of the transcription start site of the maize pericarp color1 (p1) gene. The p1
      gene encodes an R2R3 Myb-like transcription factor that regulates the flavonoid
      biosynthetic pathway in maize floral organs. Distinct p1 alleles exhibit organ
      specific expression patterns on kernel pericarp and cob glumes. A cob glume
      specific regulatory region has been identified in the distal enhancer. Further
      characterization of 6 single-copy p1 alleles, including P1-rr (red pericarp/red
      cob) and P1-rw (red pericarp and white cob), reveals 3 distinct enhancer types.
      Sequence variations in the enhancer are correlated with the p1 gene expression
      patterns in cob glume. Structural comparisons and phylogenetic analyses suggest
      that evolution of the enhancer region is likely driven by gene conversion between
      long direct noncoding repeats (approximately 6 kb in length). Given that tandem
      and segmental duplications are common in both animal and plant genomes, our
      studies suggest that recombination between noncoding duplicated sequences could
      play an important role in creating genetic and phenotypic variations.

PMID- 16816431
TI  - Effects of trans-acting genetic modifiers on meiotic recombination across the a1
      sh2 interval of maize.
AB  - Meiotic recombination rates are potentially affected by cis- and trans-acting
      factors, i.e., genotype-specific modifiers that do or do not reside in the
      recombining interval, respectively. Effects of trans modifiers on recombination
      across the approximately 140-kb maize a1-sh2 interval of chromosome 3L were
      studied in the absence of polymorphic cis factors in three genetically diverse
      backgrounds into which a sequence-identical a1-sh2 interval had been
      introgressed. Genetic distances across a1-sh2 varied twofold among genetic
      backgrounds. Although the existence of regions exhibiting high and low rates of
      recombination (hot and cold spots, respectively) was conserved across
      backgrounds, the absolute rates of recombination in these sequence-identical
      regions differed significantly among backgrounds. In addition, an intergenic hot
      spot had a higher rate of recombination as compared to the genome average rate of
      recombination in one background and not in another. Recombination rates across
      two genetic intervals on chromosome 1 did not exhibit the same relationships
      among backgrounds as was observed in a1-sh2. This suggests that at least some
      detected trans-acting factors do not equally affect recombination across the
      genome. This study establishes that trans modifier(s) polymorphic among genetic
      backgrounds can increase and decrease recombination in both genic and intergenic
      regions over relatively small genetic and physical intervals.

PMID- 16816433
TI  - The use of percutaneous suture-mediated closure for the management of 14 French
      femoral venous access.
AB  - BACKGROUND: Little has been reported regarding the utility or outcomes of femoral
      venous vascular closure using arterial suture closure devices. We describe
      results using a pre-closure approach with a 6 French (Fr) Perclose Closer S
      device in patients who underwent antegrade aortic valvuloplasty using 14 Fr
      percutaneous femoral venous access catheters. METHODS: Forty-five patients
      underwent antegrade aortic valvuloplasty and suture-mediated closure with a 6 Fr
      Perclose device. A 6 Fr Closer S suture device was preloaded into the femoral
      vein after 6 Fr sheath access, prior to insertion of a 14 Fr venous sheath. Upon
      completion of the procedure, the 14 Fr femoral venous sheath was removed through
      the existing sutures. RESULTS: Of 45 patients (mean age 82.4 years; 17 males),
      immediate hemostasis was achieved with percutaneous suture closure in 43 (95.6%).
      Only 2 failures occurred which were subsequently successfully treated with manual
      compression. No late access site bleeding occurred from sutured sites. In all
      other patients, hemostasis using a 6 Fr Perclose suture-mediated device was
      successful and immediate. There was no need for transfusion, no clinical venous
      thrombosis, and no infections occurred at the access site. Two hospital deaths
      were documented from causes unrelated to suture-mediated closure. CONCLUSIONS: In
      conjunction with 14-Fr size percutaneous sheaths during antegrade aortic
      valvuloplasty, percutaneous suturemediated closure is a highly effective method
      for achieving hemostasis. This has simplified postprocedural management in terms
      of early mobilization and diminished late access site bleeding.

PMID- 16816432
TI  - The absence of Top3 reveals an interaction between the Sgs1 and Pif1 DNA
      helicases in Saccharomyces cerevisiae.
AB  - RecQ DNA helicases and Topo III topoisomerases have conserved genetic, physical,
      and functional interactions that are consistent with a model in which RecQ
      creates a recombination-dependent substrate that is resolved by Topo III. The
      phenotype associated with Topo III loss suggests that accumulation of a RecQ
      created substrate is detrimental. In yeast, mutation of the TOP3 gene encoding
      Topo III causes pleiotropic defects that are suppressed by deletion of the RecQ
      homolog Sgs1. We searched for gene dosage suppressors of top3 and identified
      Pif1, a DNA helicase that acts with polarity opposite to that of Sgs1. Pif1
      overexpression suppresses multiple top3 defects, but exacerbates sgs1 and sgs1
      top3 defects. Furthermore, Pif1 helicase activity is essential in the absence of
      Top3 in an Sgs1-dependent manner. These data clearly demonstrate that Pif1
      helicase activity is required to counteract Sgs1 helicase activity that has
      become uncoupled from Top3. Pif1 genetic interactions with the Sgs1-Top3 pathway
      are dependent upon homologous recombination. We also find that Pif1 is recruited
      to DNA repair foci and that the frequency of these foci is significantly
      increased in top3 mutants. Our results support a model in which Pif1 has a direct
      role in the prevention or repair of Sgs1-induced DNA damage that accumulates in
      top3 mutants.

PMID- 16816434
TI  - Effects of alcoholism on coronary artery disease and left ventricular dysfunction
      in male veterans.
AB  - BACKGROUND: Heavy alcohol consumption is a well-known cause of dilated
      cardiomyopathy and hypertension, but its effects on coronary atherosclerosis are
      less well understood. The objective of this study was to compare coronary anatomy
      and left ventricular dysfunction in patients with and without alcoholism
      associated with heavy consumption. METHODS: We studied 100 consecutive alcoholic
      male patients presenting with chest pain to the Department of Veterans Affairs
      New York Harbor Healthcare System (VA) between 1994 and 2002. Alcoholism was
      defined as a history of either chronic alcohol-related pancreatitis or liver
      cirrhosis. Patients were compared to age-matched controls (n = 200) that were
      known to be nonalcoholic. All patients underwent coronary angiography. RESULTS:
      Baseline demographic characteristics were similar between the two groups. The
      prevalence of significant coronary artery disease (CAD) (defined as coronary
      arterial luminal diameter stenosis > 50%) was lower in the alcoholic group than
      in the control group (42% vs. 58%; p = 0.013). Among patients with CAD, those
      with a history of alcoholism had fewer vessels with stenoses (1.6 +/- 0.6 vs. 2.3
      +/- 0.7; p < 0.001) than the control group, and were more likely to have single
      vessel CAD (64% vs. 8%; p < 0.05). The alcoholic group also had lower mean left
      ventricular ejection fraction (LVEF) compared to the control group (43 +/- 13%
      vs. 49 +/- 9%; p < 0.001), and a higher prevalence of left ventricular
      dysfunction (LVEF < 40%; 37% vs. 13%; p < 0.05). In the alcoholic group, there
      was a lower prevalence of CAD in patients with left ventricular dysfunction as
      compared to those without left ventricular dysfunction (21% vs. 49%; p = 0.006).
      CONCLUSIONS: In a group of male VA patients presenting with chest pain,
      alcoholism was associated with a lower incidence and a lesser severity of
      angiographically-defined CAD, but had greater left ventricular dysfunction. There
      appears to be an inverse relationship between CAD and left ventricular function
      in patients with a history of heavy alcohol consumption.

PMID- 16816435
TI  - Safety of beta radiation exposure to the non-target segment: an intravascular
      ultrasound dosimetric analysis.
AB  - BACKGROUND: The use of longer radioactive seed trains to avoid geographic miss
      may lead to greater radiation exposure to distal vasculature due to the natural
      tapering of coronary arteries. The aim of this study was to use IVUS-based
      dosimetric analysis to evaluate the effect of beta-radiation on angiographically
      normal, noninjured distal segments. METHODS: We analyzed 17 in-stent restenosis
      cases (stent length: 20 +/- 8 mm) treated with a 40 mm 90Sr/Y source train. The
      prescribed dose was 18.4 Gy (reference less than or equal to 3.3 mm) or 23 Gy
      (reference > 3.3 mm) at 2 mm from the source. Noninjured, but fully radiated,
      distal reference sites were determined by angiography. Based upon the three
      dimensional vessel contours obtained at baseline, the minimum dose delivered to
      90% of plaque volume (Dv90) was determined. Vessel, plaque and lumen volumes and
      Dv90 were computed in every 2 mm subsegment (n = 52). RESULTS: On average, no
      significant serial change was observed in plaque area (5.0 +/- 2.5 mm3/mm post
      treatment to 5.6 +/- 3.1 mm3/mm at 8-month follow up; p = 0.09), vessel area
      (10.2 +/- 3.7 to 10.3 +/- 4.0 mm3/mm; p = 0.84), or lumen area (5.2 +/- 2.0 to
      4.7 +/- 1.8 mm3/mm; p = 0.19). Subsegment analysis, however, revealed a wide
      range of dose distribution, with a significant positive correlation between Dv90
      and plaque increase (p = 0.008), as well as vessel change (p < 0.001),
      representing dose-dependent positive vessel remodeling following beta radiation.
      Consequently, no significant relationship was observed between Dv90 and lumen
      change. CONCLUSIONS: Detailed IVUS-based dosimetric analysis demonstrated that
      beta radiation promoted positive remodeling, preventing lumen loss despite a mild
      increase in plaque mass on angiographically normal, noninjured distal segments.

PMID- 16816436
TI  - The utility of implantable loop recorders for diagnosing unexplained syncope in
      100 consecutive patients: five-year, single-center experience.
AB  - INTRODUCTION: The purpose of this study was to retrospectively review the 5-year
      experience of a university hospital with implantable loop recorders (ILR) for the
      diagnosis of recurrent, unexplained syncope or presyncope. METHODS: One hundred
      patients with syncope or presyncope of unknown etiology (negative tilt-table
      test, electrophysiology study and neurologic workup) underwent prolonged
      monitoring with an ILR from March 2000 to December 2004. All implants were
      performed using a first-generation (manual activation) or second-generation
      (manual plus automatic activation) ILR. RESULTS: One hundred patients (70 women,
      30 men) with a mean age of 68 +/- 18 years received the ILR. Twenty-three
      patients had coronary artery disease; 2 patients had dilated cardiomyopathy. Ten
      patients received a first-generation ILR, and 90 patients received a second
      generation ILR. After 9 +/- 8 months' follow up, ILR interrogation identified an
      arrhythmogenic etiology to the syncope/presyncope in 45 patients with 55 events.
      Eight patients had a diagnosis by ILR less than 2 months from the date of
      implantation. Twenty-six patients had documented symptomatic bradycardia
      (asystole, sinus pauses, atrial fibrillation with long pauses); 11 patients had
      episodes of sinus tachycardia with heart rates of 130 to 140 beats/minute; 2
      patients had atrial tachycardia; 5 patients had multiple episodes of nonsustained
      ventricular tachycardia (NSVT); 1 patient had sustained ventricular tachycardia,
      and 4 patients had paroxysmal supraventricular tachycardia. All arrhythmias were
      treated successfully by pacemaker/ICD implantation, radiofrequency catheter
      ablation and/or medications. One patient had seizure activity, which was detected
      by ILR as high-frequency noise. Two patients failed to activate their device, as
      it was a first-generation device. CONCLUSION: Five-year experience with the ILR
      in 100 consecutive patients confirms the utility of this device in the diagnosis
      of recurrent, infrequent, unexplained syncope or presyncope. It helped diagnose
      45% of patients with unexplained syncope with negative electrophysiologic and
      neurologic workup. Most of these patients had an arrhythmogenic etiology to their
      syncope. Medical therapy, device therapy, and/or catheter ablation helped
      successfully treat all patients with an arrhythmogenic etiology detected by ILR.

PMID- 16816437
TI  - Twelve-month results of percutaneous endovascular reconstruction for chronically
      occluded superficial femoral arteries: a quality-of-life assessment.
AB  - BACKGROUND: We report our experience on the technical feasibility and impact on
      quality of life (QOL) for angioplasty and primary stenting of chronic total
      occlusion (CTO) of the superficial femoral artery (SFA). METHODS: Forty-four
      patients (51 legs) underwent attempted percutaneous revascularization for SFA CTO
      utilizing the self-expanding nitinol SMART stent (Cordis Corp., Miami, Florida).
      The Walking Impairment Questionnaire (WIQ score range: 0 to 14,080) was used to
      assess quality of life and ankle-brachial indices (ABI) were obtained pre- and
      post-procedure. RESULTS: Successful revascularization was achieved in 90.2% of
      the cases; Mean follow up was 374 +/- 321 days. The mean occlusion length was
      15.5 +/- 9.9 cm; the mean stented segment length was 23.2 +/- 12.2 cm. The
      minimum stent diameter averaged 7.0 +/- 0.6 mm, and the maximum final balloon
      diameter averaged 5.9 +/- 0.6 mm. The mean pre- and post-intervention WIQ scores
      were 722 +/- 1503, and 8,421 +/- 5,741 (p < 0.0005), respectively. The mean delta
      WIQ was 7,405 (95% CI: 6,555 to 9,245). The mean pre- and post-intervention ABI
      were 0.61 +/- 0.18, and 0.91 +/- 0.19 (p < 0.0005), respectively. The mean delta
      ABI was 0.27 (95% CI: 0.21 to 0.33). The clinically-driven target lesion
      revascularization rate at 12 months was 11.8%. CONCLUSIONS: Chronically occluded
      SFAs can be treated by percutaneous nitinol stenting techniques with a high
      degree of success that is durable at 12-month follow up. Patients have a
      significant improvement in QOL and ABI. Repeat revascularization rates are
      reasonably low, and parallel the historical surgical data.

PMID- 16816438
TI  - Stenting the chronic totally occluded superficial femoral artery: endovascular
      clinical benefit.

PMID- 16816439
TI  - Real-time, three-dimensional localization of a Brockenbrough needle during
      transseptal catheterization using a nonfluoroscopic mapping system.
AB  - We describe a new technique that allows real-time, three-dimensional (3-D)
      localization of the Brockenbrough needle tip during transseptal catheterization
      using the EnSite NavX system. Transseptal catheterization has been traditionally
      performed using fluoroscopy, and recently, with the use of intracardiac
      echocardiography. However, even intracardiac echocardiography has the limitation
      of providing only 2-D views limited to the ultrasound plane. By displaying the
      transseptal needle on the EnSite NavX system, we achieved real-time 3-D
      localization of the needle tip within the right atrial geometry and found
      accurate visual correlation between fluoroscopy, intracardiac echocardiography
      and nonfluoroscopic 3-D cardiac mapping. This study suggests that the EnSite NavX
      system is able to provide 3-D localization of the transseptal needle during
      transseptal catheterization, and may be a useful imaging modality in this
      procedure.

PMID- 16816440
TI  - Transseptal catheterization using a nonfluoroscopic mapping system.

PMID- 16816441
TI  - Improvement in left ventricular function following successful rescue percutaneous
      coronary intervention is independent of time-to-reperfusion.
AB  - OBJECTIVE: To study the influence of clinical and angiographic factors on global
      and regional left ventricular (LV) function after rescue percutaneous coronary
      intervention (PCI) in acute myocardial infarction (AMI). METHODS: We performed
      repeat cardiac catheterization in 102 patients who underwent rescue PCI at our
      centre. Eighty-two patients had suitable baseline and follow-up ventriculograms,
      which were analyzed offline by an automated edge detection technique. RESULTS:
      The mean (standard deviation [SD]) follow-up period was 22 (15) months. PCI was
      completed in all patients between 3 to 24 hours following the onset of pain.
      Improved global and regional LV systolic function was observed in 55 (67%)
      patients, and deterioration in 27 (33%). On univariate analysis, baseline
      ejection fraction (p = 0.005) and coronary stenting (p = 0.05) were associated
      with improved LV systolic function. Preprocedure TIMI flow, postprocedure TMP
      grade, time-to-reperfusion, and use of glycoprotein (GP) IIb/IIIa inhibitors did
      not influence LV systolic function. On multivariate analysis, ejection fraction
      at the time of rescue PCI (odds ratio [95% confidence interval]: 0.427 [0.234,
      0.780]; p = 0.006) and stenting 3.944 (1.182, 13.156; p = 0.026) were predictors
      of improved LV systolic function. CONCLUSION: Successful rescue PCI was
      associated with improved LV function at follow up in the majority of patients.
      Stenting, but not GP IIb/IIIa inhibitor therapy, predicted improved LV function
      in the area supplied by the infarct-related artery. These improvements in
      regional wall motion were independent of the time taken to establish reperfusion,
      provided the intervention was carried out between 3 to 24 hours from the onset of
      pain.

PMID- 16816442
TI  - New concept for CTO recanalization using controlled antegrade and retrograde
      subintimal tracking: the CART technique.
AB  - OBJECTIVES: To demonstrate the safety and feasibility of a new concept for CTO
      recanalization using a controlled antegrade and retrograde subintimal tracking
      technique (CART technique). BACKGROUND: A successful percutaneous recanalization
      of chronic coronary occlusions results in improved survival, as well as enhanced
      left ventricular function, reduction in angina, and improved exercise tolerance.
      However, successful recanalization of CTOs is still not optimal, and needs
      further improvements. METHODS: Ten patients with a CTO underwent the CART
      procedure. This technique combines the simultaneous use of the antegrade and
      retrograde approaches. A subintimal dissection is created antegradely and
      retrogradely, which allows the operator to limit the extension of the subintimal
      dissection in the CTO portion. A retrograde approach means that the occlusion
      site is approached in a retrograde fashion through the best collateral channel
      from any other patent coronary artery. RESULTS: The occlusion site was located in
      the RCA in 9 patients, and in the LAD in 1 patient. CTO duration varied from 7 to
      84 months. Vessel recanalization was achieved in all patients. In all cases, the
      subintimal dissection was limited to the CTO region. No complications occurred in
      the collateral channel used for the retrograde approach. There were no in
      hospital major adverse cardiac events. CONCLUSIONS: The CART technique is
      feasible, safe, and has a high success rate.

PMID- 16816443
TI  - The chronic total coronary occlusion: you can get there from here.

PMID- 16816444
TI  - Desensitization for the management of clopidogrel hypersensitivity: initial
      clinical experience.
AB  - Platelet activation and aggregation play an important role in the pathogenesis of
      arterial thrombosis in coronary, cerebral and peripheral vascular beds. The
      antiplatelet agent clopidogrel has become a mainstay of treatment for patients
      with acute coronary syndromes and stroke, and to reduce ischemic complications
      after percutaneous coronary and peripheral interventions. There are, however,
      increasing numbers of reports of hypersensitivity reactions to clopidogrel. We
      present here a protocol for clopidogrel desensitization in isolated cutaneous
      reactions. Eight patients have completed the protocol successfully. Three
      subsequently underwent coronary intervention, and all are currently tolerating a
      daily clopidogrel dose a median of 7.5 months after desensitization.
      Desensitization may allow for the safe use of clopidogrel in patients with a
      history of prior cutaneous hypersensitivity reactions.

PMID- 16816445
TI  - Giant fistula between the aorta and the coronary sinus.

PMID- 16816446
TI  - Dual lumen catheters: more than just aspiration.

PMID- 16816447
TI  - Percutaneous balloon pericardiotomy for the treatment of infected pericardial
      effusion with tamponade.
AB  - Percutaneous balloon pericardiotomy has been used as an alternative for
      surgically created pericardial window mainly for the management of malignant
      pericardial effusions in critically ill patients. We describe a patient with
      purulent pericardial effusion and cardiac tamponade who was treated successfully
      and without complications with percutaneous balloon pericardiotomy.

PMID- 16816448
TI  - Simultaneous subacute stent thrombosis of two drug-eluting stents in the left
      anterior descending and the circumflex coronary arteries. Case report and review
      of the literature.
AB  - In the area of drug-eluting stents (DES), complex interventional procedures are
      increasing in number. In particular, the number of patients undergoing three
      vessel or bifurcation lesion stenting is rising, together with increasing concern
      about the risk of acute stent thrombosis in the area of the DES. In this paper,
      we present a patient who underwent multivessel bifurcation stent placement after
      an acute inferior myocardial infarction over a period of one week, with sudden
      subacute stents thrombosis of the two drug-eluting stents in the left anterior
      descending and the circumflex coronary arteries, leading to death. This case
      report is followed by a review of literature.

PMID- 16816449
TI  - Very late bare-metal stent thrombosis. A case report and review of the
      literature.
AB  - Stent thrombosis is a catastrophic event characterized by the acute thrombotic
      occlusion of a previously-stented segment of a coronary artery. It usually
      presents as an ST-segment elevation myocardial infarction and/or death, and most
      commonly occurs within the first several weeks after stent placement. Stent
      thrombosis is classified as either subacute stent thrombosis (SAT), occurring
      within 30 days of stent placement, or as late stent thrombosis (LST), occurring
      after 30 days. While very late stent thrombosis (VLST), occurring beyond 1 year,
      is not uncommon with the use of drug-eluting stents, it is distinctly unusual
      with the use of bare-metal stents. We report a case of very late thrombosis of a
      bare-metal stent occurring 717 days after implantation.

PMID- 16816450
TI  - Asymmetric septal hypertrophy complicated by dynamic left ventricular obstruction
      after intra-aortic balloon counterpulsation placement in the setting of anterior
      myocardial infarction.
AB  - We report the case of a 74-year-old patient admitted for acute anterior
      myocardial infarction and treated by intravenous thrombolysis. Because of
      hemodynamic instability, an intra-aortic balloon pump (IABP) was inserted.
      However, the patient's systolic blood pressure deteriorated early after IABP
      placement. Echocardiography revealed a dynamic left ventricular outflow tract
      obstruction occurring only during assisted ventricular systoles. Interruption of
      counterpulsation allowed complete resolution of the dynamic obstruction and
      improvement of hemodynamic status.

PMID- 16816451
TI  - A rare form of communication between the left internal thoracic artery and the
      left anterior descending artery.
AB  - Extracardiac collaterals generally from bronchial and internal thoracic arteries
      to coronary circulation have been described in the literature. In this report, we
      present a case of 59-year-old male patient with collaterals from the left
      internal thoracic artery to the left anterior descending artery developed after
      coronary artery bypass grafting and aneurysmectomy surgery. It is likely the
      collaterals developed as a result of the postoperative adhesions.

PMID- 16816452
TI  - Use of ticlopidine and cilostazol after intracoronary drug-eluting stent
      placement in a patient with previous clopidogrel-induced thrombotic
      thrombocytopenic purpura: a case report.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an extremely rare but potentially
      fatal adverse reaction to the thienopyridines, clopidogrel and ticlopidine. We
      report the case of a patient with a history of clopidogrel-induced TTP who
      subsequently was successfully treated with aspirin, ticlopidine and cilostazol
      after stenting for severe, symptomatic coronary artery disease. This case
      supports the theory that clopidogrel and ticlopidine mediate TTP through slightly
      different mechanisms and that ticlopidine may be safely used in this setting if
      absolutely necessary. Moreover, while sufficient data are lacking, the
      combination of aspirin and cilostazol in this setting may provide adequate
      antithrombotic protection long term after drug-eluting stent placement.

PMID- 16816453
TI  - Anomalous origin of the left circumflex coronary artery from the right coronary
      artery and the left anterior descending artery from the right coronary sinus.
AB  - We present the case of a 67-year-old female who was admitted to our institution
      because of anginal chest pain. Selective coronary angiography revealed separate
      ostial origins of the left anterior descending (LAD) artery and the right
      coronary artery (RCA) from the right coronary sinus (RCS). The left circumflex
      (LCx) coronary artery arose from the proximal RCA. The left anterior descending
      had an anterior free wall and the LCx had a retroaortic course. To our knowledge,
      this type of combination of anatomical variation of coronary circulation has not
      been described in the literature.

PMID- 16816455
TI  - First cluster of C. difficile toxinotype III, PCR-ribotype 027 associated disease
      in France: preliminary report.

PMID- 16816456
TI  - Outbreak of low pathogenicity H7N3 avian influenza in UK, including associated
      case of human conjunctivitis.

PMID- 16816457
TI  - Further thoughts on the limitations of a recently published review of national
      influenza pandemic plans in Europe.

PMID- 16816459
TI  - Measles outbreak in Germany: over 1000 cases now reported in Nordrhein Westfalen.

PMID- 16816460
TI  - Chikungunya risk assessment for Europe: recommendations for action.

PMID- 16816461
TI  - Mounting evidence of the efficacy of human papillomavirus vaccines.

PMID- 16816462
TI  - Cluster of trichinellosis cases in Mecklenburg-Vorpommern, Germany.

PMID- 16816463
TI  - Measles case imported from Europe to Victoria, Australia, March 2006.

PMID- 16816465
TI  - Avian influenza H5N1 outbreaks in Romanian and Danish poultry, and large H5N1
      cluster in an Indonesian family.

PMID- 16816466
TI  - HIV transmission in part of the US prison system: implications for Europe.

PMID- 16816467
TI  - [Vitamin D insufficiency in Japanese adults].
AB  - Vitamin D insufficiency has recently drawn attention as a risk factor for
      osteoporosis. This paper evaluated vitamin D insufficiency in Japanese adults.
      The prevalence of vitamin D insufficiency, defined as serum 25-hydroxyvitamin D
      (25 [OH] D) concentrations less than 30 nmol/l, among independent community
      dwelling elderly people was approximately five percent. Conversely, the
      prevalence of vitamin D insufficiency among frail, inactive elderly people with
      low levels of activities of daily living (ADL) was up to 50% greater. These
      results intimate that ADL may be an important determinant of vitamin D
      insufficiency. Overall findings highlight the need for measurement of serum 25
      (OH) D to become a more common medical examination to detect vitamin D
      insufficiency in the elderly.

PMID- 16816468
TI  - [Nutritional aspects of vitamin D].
AB  - Dietary reference intakes for Japanese, 2005 defines the adequate intake (AI) for
      vitamin D to be 5 microg (200 IU), which is higher than the previously defined
      value of 100 IU. The difference reflects that vitamin D insufficiency has come to
      be taken into account in addition to vitamin D deficiency. Some questions,
      however, still remains to be answered, such as whether these values, far lower
      than those in USA or UK, is adequate or whether AI for the elderly should be
      separately defined.

PMID- 16816469
TI  - [Effects of vitamin D on the cardiovascular system].
AB  - Active vitamin D plays important roles not only in bone and mineral metabolism
      but also in the cardiovascular system. Cohort studies in hemodialysis patients
      demonstrated that use of active vitamin D analogs was associated with reduced
      risk of death, particularly death from cardiovascular disease. Treatment with
      vitamin D had beneficial effects on cardiac and immune functions in dialysis
      patients, and inflammatory markers in non-renal subjects. Also, anti-proteinuric
      effect was recently shown in chronic kidney disease. Experimentally, active
      vitamin D inhibits atherogenic cellular behaviors and activation of the renin
      angiotensin system. Thus, active vitamin D is a regulator of cardiovascular and
      kidney functions.

PMID- 16816470
TI  - [Effect of vitamin D on bone mineral density; bone strength and fracture
      prevention].
AB  - Although vitamin D improves bone mineral density 0.66% per year at spine site and
      1.23% per year at femoral neck site, respectively, vitamin D is useful for
      preventing osteoporotic fractures, especially hip fractures in the elderly.
      Vitamin D affects microstructure and bone turnover for osteoporotic bone to
      become strong bone. And vitamin D improves muscle function to prevent falls in
      the elderly. Moreover the appropriate amount and treatment target of vitamin D
      must be considered for the elderly with many different diseases.

PMID- 16816471
TI  - [Aging and vitamin D].
AB  - Although vitamin D plays an important role in bone metabolism, various factors
      tend to reduce the production of vitamin D in the elderly women, including their
      reduced activities of daily living (ADL). There is as yet no consensus among
      researchers as to what intake level of nutrients such as calcium and vitamin D is
      appropriate for each racial group to prevent bone fractures. To judge the
      effectiveness of anti-absorptive agents, however, an understanding of sufficient
      calcium and vitamin D intake levels is fundamental. It is important to re
      evaluate both diet and the use of supplements for the elderly women.

PMID- 16816472
TI  - [Recent studies on vitamin D metabolizing enzymes].
AB  - CYP27A1, CYP27B1, and CYP24A1 are members of the cytochrome P450 superfamily, and
      key enzymes of vitamin D(3) metabolism. CYP27A1 produced at least seven forms of
      minor metabolites including 1alpha, 25 (OH) (2)D(3) in addition to the major
      metabolite 25 (OH) D(3). In contrast, CYP27B1 appears to be a special enzyme to
      catalyze the hydroxylation at C-1alpha position of 25 (OH) D(3). Mutagenesis
      studies of CYP27B1 revealed the amino acid residues involved in substrate binding
      or interaction between CYP27B1 and adreno-doxin. On CYP24A1-dependent metabolism,
      remarkable metabolic processes of 1alpha, 25 (OH) (2)D(3) were observed. Rat
      CYP24A1 catalyzed six sequential monooxygenation reactions that convert 1alpha,
      25 (OH) (2)D(3) into calcitroic acid. In addition to the C-24 oxidation pathway,
      human CYP24A1 catalyzed also C-23 oxidation pathway to produce 1alpha, 25 (OH)
      (2)D(3)-26, 23-lactone. Surprisingly, more than 70% of the vitamin D metabolites
      observed in a living body were found to be the products formed by the activities
      of CYP27A1, CYP27B1, and CYP24A1. In addition to the mitochondrial P450s,
      microsomal P450s also play important roles in vitamin D metabolism. Recent
      reports suggest that human microsomal CYP2R1 is more important than CYP27A1 as a
      vitamin D 25-hydroxylase. The decline in bone mineral density that occurs after
      long-term treatment with some antiepileptic drugs appears to be due to the
      increased 1alpha, 25 (OH) (2)D(3) metabolism by CYP3A4. Some vitamin D analogs
      are good substrates for CYP3A1 while CYP24A1 is responsible for metabolism of
      most of vitamin D analogs.

PMID- 16816473
TI  - [Vitamin D and phosphate metabolism; relationship with aging-regulating gene].
AB  - It has been known that phosphate homeostasis is mainly regulated by parathyroid
      hormone and vitamin D. Fibroblast growth factor 23 (FGF23) has been identified as
      a novel factor that regulates vitamin D and phosphate metabolism. Genetic defect
      of FGF23 in mice revealed not only abnormal vitamin D and phosphate metabolism,
      but also premature aging-like phenotype that is quite similar to Klotho mice.
      Regulation of vitamin D and phosphate metabolism is closely related to aging
      processes as well as bone and mineral metabolism.

PMID- 16816474
TI  - [Vitamin D metabolism and chronic kidney disease].
AB  - Vitamin D is finally converted into the active form in the kidney, which is
      regulated and affected by several factors such as calcium . phosphate balance,
      parathyroid hormone (PTH), calcitonin and fibroblast growth factor 23 (FGF23).
      Activated vitamin D works as hormone and engages in calcium . bone metabolism. In
      chronic kidney disease, the active form can be decreased and therefore, renal
      osteodystrophy can be lead as consequences of mineral metabolism abnormality and
      unregulated PTH production/secretion as increased activity of the parathyroid
      glands (2HPT). Moreover, because chronic kidney disease (CKD)-associated abnormal
      states in above are detrimental to CKD patients not only in terms of renal
      osteodystrophy, but progress of cardiovascular disease and mortality. Therefore
      new concept is proposed as chronic kidney disease-mineral bone disorder (CKD
      MBD).

PMID- 16816475
TI  - [Vitamin D and cancer].
AB  - Vitamin D is a steroid hormone which regulates calcium and bone homeostasis
      through intestine, bone, kidney and parathyroid. It has been reported that
      vitamin D inhibits the cancer incidence and tumor growth. In this review, we
      summarize the epidemiological, animal and clinical research of vitamin D on
      breast, colon and prostate cancer.

PMID- 16816476
TI  - [Recent progress of study on vitamin D analogs].
AB  - Separation of inducing cell differentiation and antiproliferative activities as
      well as immunoregulatory effects from calcemic activity of the natural hormone,
      1alpha,25-dihydroxyvitamin D(3) [1alpha,25 (OH) (2)D(3)] , utilizing the
      synthetic 1alpha,25 (OH) (2)D(3) analogs has been studied over 20 years. During
      the past two decades, progress of molecular biology taught us the precise action
      mechanisms of 1alpha,25 (OH) (2)D(3) through its specific receptor to express the
      target genes on the molecular level. Modification at the CD-ring side chain of
      1alpha,25 (OH) (2)D(3) is the most common chemical conversion, and the
      alternative approach is A-ring and/or CD-ring modifications. With these chemical
      functionalizations, some vitamin D analogs are clinically used as medicines or
      promising candidates for treating secondary hyperparathyroidism, psoriasis, and
      osteoporosis. Although 1alpha,25 (OH) (2)D(3) can inhibit the growth of various
      human cancers and regulate the human immune system, primary side effect of
      1alpha,25 (OH) (2)D(3) is its tendency to raise serum calcium levels and to cause
      hypercalcemia, which should be avoided. With these backgrounds, we discuss here
      recent progress on synthetic vitamin D analogs.

PMID- 16816477
TI  - [Progress in research on vitamin D analogs].
AB  - A little over two decades ago, the vitamin D activation pathway was elucidated
      and alfacalcidol arrived on the scene as a prodrug for active vitamin D, 1,25
      dihydroxyvitamin D(3), to remedy vitamin D deficiency. With the concurrent
      reported discovery of the differentiation-inducing effect of active vitamin D,
      its diverse physiological effects have become appreciated and the research aiming
      to accentuate selected physiological effects by analog research has made a fresh
      development. Our studies aimed particularly at separating the differentiation
      inducing effect/cell growth-inhibitory effect and the calcemic effect of active
      vitamin D led to the development of two characteristic analogs, OCT and ED-71.
      OCT, characterized by its profound differentiation-inducing effect and modest
      calcemic effect, is currently in practical use as an injectable therapeutic agent
      for secondary hyperparathyroidism as well as in clinical settings as an ointment
      for the treatment of psoriasis vulgaris. The other analog, ED-71, possesses a
      profile inverse to that of OCT and is now under clinical development as an oral
      preparation for treatment of osteoporosis. The present overview refers to
      methodology of searching next-generation analogs, exemplifying a new analog, DD
      281, based on the knowledge accumulated through development of OCT and ED-71.

PMID- 16816478
TI  - [Vitamin D-vitamin D receptor system regulates antithrombogenicity in vivo].
AB  - Although it has been well documented that vitamin D receptor (VDR) activation
      influences the expression of various genes involved in calcium homeostasis and
      cell differentiation, the physiological role of VDR action in hemostasis remains
      unclear. We studied thrombogenicity in normocalcemic VDR knock-out (KO) mice on a
      high calcium diet in comparison with that in wild-type mice and that in
      hypocalcemic VDRKO mice fed a regular diet. Platelet aggregation was
      significantly enhanced in normocalcemic VDRKO mice. Aortic endothelial nitric
      oxide (NO) synthase expression and urinary NOx excretion were reduced in
      hypocalcemic VDRKO mice but not in normocalcemic VDRKO mice. The gene expression
      of antithrombin in the liver and that of thrombomodulin in the aorta, liver and
      kidney were down-regulated in hypo- and normocalcemic VDRKO mice, whereas tissue
      factor gene expression in the liver and kidney was up-regulated in VDRKO mice
      regardless of plasma calcium level. Furthermore, VDRKO mice manifested an
      exacerbated multi-organ thrombus formation after exogenous lipopolysaccharide
      injection regardless of the calcemic conditions. These results demonstrate that
      the vitamin D-VDR system plays a pivotal role in antithrombogenicity in vivo.

PMID- 16816479
TI  - [Effect of vitamin D on the nervous system and the skeletal muscle].
AB  - The presence of vitamin D receptors (VDRs) in the brain suggest that vitamin D
      had functions in this organ and accumulating data have provide evidence that this
      is indeed the case. Recently, it has been recognized that vitamin D behaves as a
      neuroactive compound (neurosteroid) largely implicated in the control of brain
      homeostasis. Likewise, the neuroprotective effects of vitamin D, achieved by its
      action levels of nerve growth factors in the treatment of neurodegenerative
      disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Recent
      studies on VDR gene knockout mice revealed that VDR also regulates behavioural
      characterization and differentiation of skeletal muscle. Thus, vitamin D appears
      to regulate development and homeostasis of the nervous system and skeletal
      muscle.

PMID- 16816480
TI  - [Requirement of 25-hydroxyvitamin D in prevention of osteoporosis based on a
      pathophysiological perspective].
AB  - Vitamin D insufficiency is one of the risk factors of osteoporosis. Secondary
      hyperparathyroidism induced by low serum concentration of 25-hydroxyvitamin D (25
      D), which is a most important nutritional marker to evaluate vitamin D status,
      results in bone loss and increase of fracture risk. In this topic, the recent
      findings related to the circulating concentration of 25-D for the prevention of
      osteoporosis are reviewed.

PMID- 16816481
TI  - [Fall-preventing effect of vitamin D].
AB  - It is well established that activated vitamin D(3) affects bone metabolism and
      its bone fracture reducing effect is prominent considering relatively weak effect
      on increase of bone mineral density. The risk of osteoporotic bone fracture
      generally correlates with bone mineral density. On the other hand, fall is a
      major cause of bone fracture in the elderly people. Therefore, bone fracture
      reducing effect of activated vitamin D(3) can be presumed as the result of
      reduction of fall incidents (such as the effects on the stability of body balance
      and muscle strength), as well as the effects on bone strength and quality. In
      this manuscript, the relation between fall, bone fracture and vitamin D would be
      introduced.

PMID- 16816482
TI  - [Active vitamin D3 therapy for gulucocorticoid-induced osteoporosis].
AB  - Glucocorticoid-induced osteoporosis (GIO) is the most common secondary cause of
      osteoporosis. The use of glucocorticoid (GC) is associated with an increase in
      bone loss, especially at vertebral spine, and risk of fracture. Active vitamin
      D(3) (VD(3)) is expected to preserve bone mineral density at vertebral spine,
      however it is inferior to bisphosphonates (BP) with respect to preventing
      incidental vertebral fractures. In the guidelines on the management and treatment
      of GIO in Japan, VD(3) is recommended as the second-lined drug for GIO. The
      combination of VD(3) and BP is thought to be a beneficial therapy in prevention
      and or treatment of GIO.

PMID- 16816483
TI  - [Vitamin-D analogues for osteoporosis].
AB  - Vitamin Ds are among the drugs for osteoporosis with the longest history.
      Recently, novel properties are being found in vitamin Ds and new analogues are
      under development. Especially, ED-71 developed in Japan has advantageous actions
      in the osteoporosis treatment and will be used clinically soon.

PMID- 16816484
TI  - [Matrix gene regulation in cartilage].
AB  - Regulation of Col2a1 is a key event in the cartilage development. Many factors
      including cell adhesion, hypoxia, growth factors or cytokines regulate various
      transcription factors or co-factors which influence the expression of Col2a1.
      Sox9 is a key transcriptional activator that is involved in most of these events
      by cooperating or interfering with these factors. The balance of positive and
      negative regulators determines the level of matrix gene expression.

PMID- 16816485
TI  - [Histological function of PTHrP in cartilage].
AB  - Parathyroid hormone-related peptide (PTHrP) is known as an important local factor
      for chondrogenesis, promoting chondrocyte proliferation and inhibiting their
      differentiation into the hypertrophic phenotype. Signaling transduction through
      the PTH/PTHrP receptor has two possible pathways: the activation of adenylate
      cyclase and subsequent protein kinase A (PKA), and the activation of
      phospholipase C (PLC). Recent studies with mice carrying PTH/PTHrP receptor
      inactivated for PLC and chondrocyte-specific deletion of the G (s) gene have
      shown that cAMP/PKA signaling appears to stimulate chondrocyte proliferation and
      inhibit their differentiation, whereas PLC signaling enhanced chondrocyte
      differentiation and inhibited their proliferation. In a physiological state,
      cAMP/PKA signaling may predominate over PLC pathway. Also, Na(+)/H(+)exchanger
      regulatory factor 2 (NHERF2) has been reported to down-regulate adenylate cyclase
      activity, in a switch mechanism that results in signal transduction through the
      PLC pathway.

PMID- 16816486
TI  - Montelukast in pediatric asthma management.
AB  - Leukotriene modifiers (receptor antagonist and biosynthesis inhibitor) represent
      the first mediator specific therapeutic option for asthma. Montelukast, a
      leukotriene receptor antagonist is the only such agent approved for use in
      pediatric patients. Montelukast modifies action of leukotrienes, which are the
      most potent bronchoconstrictors, by blocking Cysteinyl leukotriene receptors.
      Systemic drug like mountelukast can reach lower airways and improves the
      peripheral functions which play a crucial role in the evolution of asthma. Review
      of existing literature showed that montelukast compared to placebo has proven
      clinical efficacy in better control of day time asthma symptoms, percentage of
      symptom free days, need for rescue drugs and improvement in FEV 1. Studies also
      demonstrated improvement in airway inflammation as indicated by reduction in
      fractional exhaled nitric oxide, a marker of inflammation. Studies comparing low
      dose inhaled corticosteroids (ICS) with montelukast are limited in children and
      conclude that it is not superior to ICS. For moderate to severe persistent
      asthma, montelukast has been compared with long acting beta agonists (LABA) as an
      add-on therapy to ICS, montelukast was less efficacious and less cost-effective.
      It has beneficial effects in exercise induced asthma and aspirin-sensitive
      asthma. Montelukast has onset of action within one hour. Patient satisfaction and
      compliance was better with montelukast than inhaled anti-inflammatory agents due
      to oral, once a day administration. The recommended doses of montelukast in
      asthma are- children 1-5 years: 4 mg chewable tablet, children 6-14 years: 5mg
      chewable tablet, ADULTS: 10mg tablet; administered once daily. The drug is well
      tolerated. Based on the presently available data montelukast may be an
      alternative treatment for mild persistent asthma as monotherapy where ICS cannot
      be administered. It is also an alternative to LABA as an add-on therapy to ICS
      for moderate to severe persistent asthma. The other indications for use of
      montelukast include: allergic rhinitis, exercise induced bronchoconstriction and
      aspirin-induced asthma.

PMID- 16816487
TI  - Transient evoked otoacoustic emissions.
AB  - OBJECTIVE: The purpose of this study was to collect parametric measures of TEOAEs
      in normal hearing children of various age-groups and to establish a normative
      baseline for Transient Evoked Otoacoustic Emissions (TEOAEs). METHODS: Sixty
      subjects were investigated in three age-groups: neonates, 0-1 month; infants, 1
      month-1 year; and children, 1-6 years. Each group comprised of 20 subjects. All
      the subjects underwent medical examination by a pediatrician and an ENT surgeon.
      Screening for hearing was done by immittance testing, behavior observation and
      conditioned play audiometry. The TEOAEs were analyzed for the parameters of
      amplitude, cross-correlation (wave reproducibility) and signal-to-noise ratio
      (SNR). RESULTS: There was no difference between the mean amplitudes of the right
      and left ears in the groups. The females in the neonates group had higher
      emission amplitudes than the males. The mean amplitude of the subjects in the
      neonates group was significantly higher than the subjects in the infants or
      children groups. The cross correlation (wave reproducibility) was constant across
      the age. The mean SNR for all the subjects were well above 3 dB at frequencies
      1.5 k, 2 k, 3 k and 4 kHz. The neonates group showed the lowest SNR ranging
      between 3.47 to 9.62 dB. The infants group showed the highest SNR ranging between
      6.13 to 13.11 dB. CONCLUSION: The TEOAEs response measures of SNR and cross
      correlation, at frequency bands 1.5, 2, 3 and 4 kHz, may provide more reliable
      outcomes than TEOAEs amplitude. Subjects in the age range of 0-1 month show lower
      SNRs than those in higher age ranges. The values can be used as normative data
      for screening and diagnostic purposes in the pediatric population.

PMID- 16816488
TI  - Urorectal septum malformation sequence: ultrasound correlation with fetal
      examination.
AB  - OBJECTIVES: To correlate prenatal and postnatal findings of urorectal septum
      malformation sequence and to study spectrum of malformation. METHODS: Nine cases
      were reviewed with features suggestive of urorectal septum malformation (URSM)
      sequence. Associated anomalies were studied. Sex of the fetus was assigned by
      karyotype when available or by examination of internal genitalia. RESULTS: Out of
      nine cases 5 fetuses were male and 4 were female. Gestational age ranged from 14
      to 34 weeks. Six cases were complete URSM sequence and 3 were partial URSM
      sequence. Associated anomalies of other systems were seen in 4 cases. In one case
      karyotype was 47, XXY. CONCLUSION: Cases with severe oligohydromnios with or
      without distended bladder, URSM sequence should be suspected, as this condition
      is usually lethal. Non-visualization of bladder, presence of hydronephrosis,
      multicystic kidneys or distended gut loops suggests the possibility of URSM
      sequence. The confirmation of diagnosis is possible after autopsy. Associated
      malformation of other organs and deformation due to oligohydromnios are commonly
      present.

PMID- 16816489
TI  - Grandmothers' influence on child care.
AB  - OBJECTIVE: This paper compares child care-giving and child's nutritional status
      among rural families where grandmothers were present and those where grandmothers
      were absent. METHODS: From 27 villages in rural Vadodara, four were randomly
      selected and all the families (n=31) with children (3-24 months) where
      grandmothers were present (GMP) were compared with 39 families where grandmothers
      were absent (GMA). Semi structured questionnaires were used to assess beliefs
      practices of mothers and grandmothers regarding breastfeeding and complementary
      feeding (BF-CF). Nutrient intake of the children and nutritional status were
      measured using standard procedures. RESULTS: Some deleterious practices were
      present in a similar proportion of both GMP and GMA groups: giving prelacteals,
      delaying initiation of BF, exclusive breastfeeding < 3 months and delaying
      initiation of CF. Favorable practices present in significantly more GMP were:
      active feeding and use of anganwadi services. Grandmother's help enabled mother
      to practice more care-giving behaviors. However, children in both the groups had
      low calorie intake CONCLUSION: Role of family members in childcare and the
      benefits of including them in interventions to improve child survival, health and
      nutrition status need to be further researched.

PMID- 16816490
TI  - Adolescents with attention deficit and hyperactivity disorder/learning disability
      and their proneness to accidents.
AB  - OBJECTIVE: The aim of the study was to determine if attention deficit and
      hyperactivity disorder (ADHD)/ learning disability (LD) adolescents are more
      prone to accidents and to investigate the parental mode of coping with that risk.
      METHODS: One hundred and eight high school pupils diagnosed with ADHD/LD and
      studying in an institute of "special education" were examined and interviewed on
      the subject of accidents. Eighty-seven pupils, studying in a nearby academic high
      school, served as a control group. RESULTS: The results showed that pupils in the
      study group had been involved in 0.57 +/- 1.6 accidents (until the present study)
      in comparison to 0.23 +/- 0.4 accidents in the control group (p=0.001). The
      accidents in the ADHD/LD study group had occurred at the mean age of 11.1 +/- 3.4
      yr. Eight decimal three percent of these pupils had been involved in recurrent
      accidents. Circumstances and locations where the accidents occurred were: falls
      while running or participating in sports activities (38.5%), home environment
      (23%), school environment (19.2%) and road accidents (11.5%). CONCLUSION: The
      study shows that there is a real risk for ADHD/LD adolescents to be involved in
      all kinds of accidents. Parents should be counting on the help of professional
      advisors to decrease that risk. Physicians should caution these adolescents and
      their parents about that risk and advise them on ways and means of accident
      prevention.

PMID- 16816491
TI  - Penicillin and gentamicin therapy vs amoxicillin/clavulanate in severe hypoxemic
      pneumonia.
AB  - OBJECTIVE: To compare the efficacy of sequential injectable crystalline
      penicillin (C.pen) and gentamicin combination followed by oral amoxicillin with
      sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe
      or very severe hypoxemic pneumonia. METHODS: Children aged 2-59 months with WHO
      defined severe or very severe pneumonia with hypoxemia (SpO2 < 90%) were included
      in the study. Patients with fever > 10 days, bacterial meningitis, prior
      antibiotic therapy > 24 hours, stridor, heart disease and allergy to any of the
      study drugs were excluded. They were randomly allocated to two groups--Group A
      and Group B. Group A received C. pen and gentamicin intravenously (IV), followed
      by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav.
      Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate,
      oxygen saturation and chest wall indrawing were monitored 6 hourly. RESULTS: 71
      patients were included. There were two (5.2%) blood cultures positive in group A
      and three (9%) in group B. Organisms isolated were S. pneumoniae (n=3) and H.
      influenzae-b (n=2). There was only one treatment failure in each of the groups.
      One was due to penicillin resistant H. influenzae -b and the other was due to
      worsening of pneumonia. The mean time taken for normalization of tachypnea,
      hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean
      duration of IV therapy in group A was 76+/-25 hrs and group B was 75+/-24 hrs
      (p>0.1). CONCLUSION: In children of 2-59 months, sequential injectable C. pen and
      gentamicin combination, followed by oral amoxicillin or sequential IV and oral
      amox-clav were equally effective for the treatment of severe or very severe
      hypoxemic community acquired pneumonia.

PMID- 16816493
TI  - New antiviral agents.
AB  - During the last three decades, a better understanding of viral replication and
      disease states caused by viral infections have led to the development of newer
      antiviral agents with enhanced activity and better tolerability. This review
      focuses on newer systemic and topical antiviral agents that are used in treatment
      of herpes viruses including herpes simplex type-1 (HSV-1) and type-2 (HSV-2),
      varicella-zoster virus (VZV) and cytomegalovirus CMV) as well as the human
      papilloma virus (HPV). Included in this article are the agents famciclovir,
      penciclovir, valganciclovir, imiquimod, docosanole and brivudin.

PMID- 16816494
TI  - Antibiotics for treatment of resistant gram-positive coccal infections.
AB  - Vancomycin is considered the workhorse for the treatment of most drug-resistant
      gram-positive bacterial infections. However, concerns have been raised regarding
      the increasing rates of vancomycin-resistant enterococci and the clinical
      shortcomings of vancomycin in the treatment of invasive Staphylococcus aureus
      infections. Resources have been committed to the development of antimicrobial
      agents with activity against these organisms. This review will focus on the newer
      antibacterial agents that have been developed for the treatment of resistant gram
      positive pathogens. Included in this review are the agents: quinupristin
      dalfopristin, linezolid, daptomycin, telithromycin, and tigecycline.

PMID- 16816495
TI  - New antiretroviral drugs in clinical use.
AB  - The advent of combination antiretroviral therapy for the treatment of human
      immunodeficiency virus (HIV) infection has dramatically changed the prognosis and
      quality of life of HIV-infected adults and children. To date, there are 21
      antiretroviral agents available with only 11 agents being approved for the use in
      young children less than 6 years of age. The currently available antiretroviral
      agents belong to four different classes; nucleoside/nucleotide reverse
      transcriptase inhibitors (NRTI, NtRTI), non-nucleoside reverse transcriptase
      inhibitors (NNRTI), protease inhibitors (PI), and a new class of fusion
      inhibitors (FI). It is recommended that the treatment regimen should be a
      combination of at least 3 drugs from different drug classes as this has been
      shown to slow disease progression, improve survival, and result in better
      virologic and immunologic responses. Treatment with antiretroviral agents is
      frequently complicated by the issues of adherence, tolerability, long term
      toxicity and drug resistance. Many efforts have been made to develop new
      antiretroviral agents with greater potency, higher tolerability profiles and
      better convenience. Some new agents are also effective against drug-resistant
      strains of HIV. Since 2001, there were 7 new antiretroviral agents and 2 fixed
      dose multidrug formulations being approved for the treatment of HIV infection,
      most are approved only for use in adults. In this article, we will review new
      antiretroviral agents including emtricitabine, tenofovir disoproxil fumarate,
      atazanavir, fosamprenavir, tipranavir and enfuvirtide. Pediatric information on
      these drugs will be provided when available.

PMID- 16816496
TI  - The judicious use of antibiotics--an investment towards optimized health care.
AB  - During the past century the excitement of discovering antibiotics as a treatment
      of infectious diseases has given way to a sense of complacency and acceptance
      that when faced with antimicrobial resistance there will always be new and better
      antimicrobial agents to use. Now, with clear indications of a decline in
      pharmaceutical company interest in anti-infective research, at the same time when
      multi-drug resistant micro-organisms continue to be reported, it is very
      important to review the prudent use of the available agents to fight these micro
      organisms. Injudicious use of antibiotics is a global problem with some countries
      more affected than others. There is no dearth of interest in this subject with
      scores of scholarly articles written about it. While over the counter access to
      antibiotics is mentioned as an important contributor towards injudicious
      antibiotic use in developing nations, as shown in a number of studies, there are
      many provider, practice and patient characteristics which drive antibiotic
      overuse in developed nations such as the United States. Recognizing that a
      thorough review of this subject goes far and beyond the page limitations of a
      review article we provide a summary of some of the salient aspects of this global
      problem with a focus towards readers practicing in developing nations.

PMID- 16816497
TI  - Harlequin ichthyosis.

PMID- 16816498
TI  - Yunis Varon syndrome.
AB  - In this communication is reported a neonate with Yunis Varon syndrome, a rare
      autosomal recessive disorder, born to a consanguineously married couple who had
      microcephaly, wide cranial sutures, prominent eyes, hypertelorism, dysplastic
      ears, sparse hairs, cupid bow like upper lip with median pseudocleft and labio
      gingival retraction. Bilateral hypoplasia of thumbs, absent great toes, short
      phalanges were other features. Additional features in this case included median
      pseudocleft unreported earlier and C.T. findings of underdeveloped gyri, ischemic
      changes in temperoparietal region and bilateral lacunar infarcts in middle
      cerebral artery territory.

PMID- 16816499
TI  - Precocious pseudopuberty with testicular enlargement.
AB  - Gonadotropins independent precocious puberty (GIPP) in male is characterized by
      early appearance of sexual hairs and phallic growth but without testicular
      enlargement. We report a case of GIPP with testicular enlargement who was
      diagnosed to have testotoxicosis and successfully managed with spironolactone.

PMID- 16816500
TI  - Naxos disease.
AB  - Naxos disease (OMIM 601214) characterized by wooly hair, palmoplantar keratoderma
      and dilated cardiomyopathy in two Indian children of the same family is
      described.

PMID- 16816501
TI  - Bilateral ocular scrofuloderma with orbital tuberculosis.
AB  - Ocular scrofuloderma with orbital tuberculosis is a rarely described presentation
      of childhood tuberculosis. Bilateral involvement has not been reported earlier in
      the medical literature. Here is reported a 3-year-old boy who presented with
      bilateral infraorbital swellings of tubercular etiology. Computed tomography (CT)
      scan of the upper face revealed enhancing soft tissue lesions in both the lower
      lids of the eyes, with extraconal extension into the orbits and with erosion of
      the right zygomatic bone. Tubercular etiology was confirmed by the Ziehl Neelsen
      staining of the aspirate from the lesion, which was positive for acid-fast
      bacilli and growth of Mycobacterium tuberculosis in the aspirate culture. The
      patient showed marked improvement of his lesions on anti-tubercular treatment.

PMID- 16816502
TI  - Incomplete duodenal obstruction in a newborn.
AB  - A case of newborn with incomplete duodenal obstruction caused by superior
      mesenteric artery syndrome has been presented with this report. A full term, 1
      day-old baby girl was referred to our hospital because of recurrent bilious
      vomiting since birth and upper gastrointestinal barium study revealed the
      incomplete obstruction at the 3rd part of the duodenum with a vertical abrupt
      cutoff. The diagnosis of superior mesenteric artery syndrome was made with
      ultrasonography and duodenojejunostomy was carried out. Although it is extremely
      rare, superior mesenteric artery syndrome should also be considered as one of the
      rare cause of incomplete duodenal obstruction in newborn period.

PMID- 16816503
TI  - Surgical reconstruction for absence of sternum and pericardium in a newborn.
AB  - We report the surgical management of a 3 day old baby with absent sternum and
      pericardium with impending rupture of the skin cover. The repair described is
      innovative and may be used in place of primary repair by bringing the ribs
      together. Review of embryology and various modalities of closure are provided.

PMID- 16816504
TI  - Infected mature teratoma of lower posterior mediastinum.

PMID- 16816505
TI  - Intracranial Hodgkin's disease.

PMID- 16816506
TI  - Combating poster fatigue.

PMID- 16816507
TI  - PG thesis: idealistic vs realistic.

PMID- 16816508
TI  - Child survival in India.
AB  - About 2.1 million Indian children under 5 years of age die each year. In spite of
      reductions in child mortality rate over the past two decades, the rate remains
      high at 87 per 1000 live births. The main causes are diarrhoea, pneumonia, and
      for deaths among the neonates asphyxia, pre-term delivery, sepsis and tetanus.
      The major underlying cause of death is undernutrition. Child survival
      interventions of proven impact, feasible for use at high coverage in India were
      identified, and their effect on child mortality was calculated if high coverage
      were to be achieved. Exclusive breastfeeding, oral rehydration therapy, and
      adequate complementary feeding were among the most effective interventions. If
      these interventions would be applied universally 57% of mortality among pre
      schoolers could be prevented. No cause specific mortality data were available
      from individual Indian states. Nevertheless, the range of child mortality, as
      well as the proportion of neo-natal deaths, occurring across the states, suggests
      that at state level 50-70% of deaths can be prevented. The results show that the
      targets set in the millennium development goals as well as in the Tenth Five Year
      plan can be reached.

PMID- 16816509
TI  - Immunological response to two hepatitis B vaccines administered in two different
      schedules.
AB  - OBJECTIVES: To evaluate the antibody response to a plasma derived hepatitis B
      vaccine containing pre-S and S antigens and a recombinant vaccine containing only
      S antigen and compare the two vaccines in 0, 1, 2 and 0, 1, 6, schedules METHODS:
      One hundred fifty nine healthy infants were randomized to receive the vaccines in
      two different schedules. Anti HBs titers were estimated prior to the vaccination
      and then one-month following the second and third doses. RESULTS: Both the
      vaccines produced a high rate of seroconversion and seroprotection. The antibody
      response was similar with both the vaccines and the 0, 1, 6, schedule induced a
      significantly higher antibody level than the 0, 1, 2, schedule. CONCLUSION: 0, 1,
      6 schedule produces a higher antibody level than 0, 1, 2 schedule though both the
      schedules have good seroconversion and seroprotection rates with both the
      vaccines.

PMID- 16816510
TI  - Zinc supplementation and serum zinc during diarrhea.
AB  - OBJECTIVE: Zinc deficiency is very common in developing countries and is more
      pronounced during an episode of diarrhea. Supplementation with zinc improves
      diarrhea and might correct zinc deficiency in both the short and longer term.
      METHOD: We conducted a nested study within a cluster randomized treatment trial.
      Fifty children with diarrhea living in the zinc treated clusters, 50 children
      with diarrhea living in control clusters, and 50 healthy children living in the
      control clusters were enrolled. We assessed serum zinc at the start of the
      diarrhea episode, which was 1-3 days after supplementation began in zinc treated
      children, and again one week after the diarrhea ended and supplementation ceased.
      Baseline characteristics and serum zinc concentration were assessed. RESULTS:
      Serum zinc was low in 44% of healthy children at the first blood draw. Compared
      to healthy controls, serum zinc was 3.1 mmol/L higher among children with
      diarrhea who were supplemented with zinc at first blood draw and 1.3 mmol/L
      higher 3 weeks later. CONCLUSION: Zinc supplementation enhances serum zinc
      concentration when given as a treatment for diarrhea and helps children maintain
      a more adequate zinc status during the convalescent period.

PMID- 16816511
TI  - Acute renal failure in neonatal sepsis.
AB  - OBJECTIVE: To evaluate the occurrence of acute renal failure (ARF) and the
      factors associated with it in cases of neonatal sepsis. METHODS: The case control
      study was conducted in the referral neonatal intensive care unit of a tertiary
      teaching hospital. 200 out born neonates with sepsis admitted to the nursery from
      January to July 2003 were evaluated for presence of ARF (cases) or not
      (controls). Sepsis was diagnosed on the basis of either a positive sepsis screen
      (immature: total (I:T) neutrophil ratio > 0.2, micro-ESR > age in days + 2 mm or>
      15 mm, CRP> 6 mg/dl, TLC< 5000 cells/mm3; 2 or more positive) or a positive blood
      culture in symptomatic neonates. ARF was defined as blood urea nitrogen (BUN)>
      20mg/dl on two separate occasions at least 24 hours apart. Oliguria was defined
      as urine output < 1 ml/Kg/hr. RESULTS: 52 out of 200 (26%) neonates with sepsis
      had ARF; only 15% of ARF was oliguric. The mean gestation of neonates with ARF
      was similar to those without ARF (36.1+/-4.1 wks vs. 36.6+/-3.5 wk; p = 0.41). A
      significantly higher number of babies with ARF weighed less than 2500 gm as
      compared to those without ARF (86.5% vs 67.6%; p = 0.008). The association of
      meningitis, disseminated intravascular coagulation (DIC) and shock was also
      significantly higher in neonates with ARF (46.8% vs 26.2%, p = 0.01; 65.4% vs
      20.3%, p < 0.001; 71.2% vs 27.0%, p < 0.001 respectively). Mortality in neonates
      who developed ARF was significantly higher (70.2% vs 25%, p < 0.001). Factors
      including gestational age, weight, onset of sepsis, culture positivity,
      associated meningitis, asphyxia, shock, prior administration of nephrotoxic drugs
      were subjected to univariate analysis for prediction of fatality in neonates with
      sepsis and ARF; only shock was found to be a significant predictor of fatality
      (p< 0.001). ARF had recovered in 22 out of 49 neonates in whom data was
      available; three patients had left against medical advice. The mean duration of
      recovery in these 22 neonates was 5.5 days (range 1-14 days). Presence of co
      existing morbidities (perinatal asphyxia/congestive heart failure (CHF)/
      necrotising enterocolitis (NEC)) or nephrotoxic drugs did not alter the frequency
      of recovery of ARF in septic neonates (45.5% vs 44.4%,p = 0.944; 41% vs 52%, p =
      0.308 respectively). CONCLUSION: Renal failure occurred in 26% neonates with
      sepsis. Although ARF in neonates has been reported to be predominantly oliguric,
      it was observed that ARF secondary to neonatal sepsis was predominantly non
      oliguric. Low birth weight was an important risk factor for the development of
      ARF. The mortality being three times higher in neonates with ARF demands a
      greater awareness of this entity among practitioners and better management of
      this condition.

PMID- 16816512
TI  - Evaluation of total plasma homocysteine in Indian newborns using heel-prick
      samples.
AB  - OBJECTIVE: To estimate total plasma homocysteine levels in Indian newborns by
      modifying the existing SBD-F based High performance liquid chromotography (HPLC)
      method in order to enable analysis in newborn heel-prick samples and assess the
      prevalence of hyperhomocysteinemia in Indian newborns who are exclusively breast
      fed. METHODS: Reverse-phase HPLC with fluorescence detection for plasma
      homocysteine estimation and statistical analysis using student t-test. RESULTS:
      SBD-F based HPLC method was modified and Bland and Altman analysis was carried
      out to assess agreement between original and modified methods. The correlation co
      efficient was 0.994. The limits of agreement (-5.9, 6.3) were small enough to
      apply new method in place of the old for heel-prick sample analysis. Total plasma
      homocysteine analysis was carried out on heel-prick samples of 607 randomly
      selected newborns (331 males and 276 females). The mean plasma homocysteine
      estimated by this method in Indian newborns was 6.99 (95% CI: 6.48-7.49) with no
      appreciable gender effect (P=0.74). Elevated homocysteine levels were observed in
      31 males and 21 females. CONCLUSIONS: Modified HPLC method is validated and can
      be used for homocysteine analysis on newborn heel-prick samples. Using this
      method, the prevalence of hyperhomocysteinemia in Indian newborns is 8.6%.

PMID- 16816513
TI  - Reproductive health problems and help seeking behavior among adolescents in urban
      India.
AB  - OBJECTIVE: To assess their reproductive health problems and help seeking
      behaviour among urban school going adolescents. METHOD: A sample of 300 urban
      school going adolescents between 11-14 years were chosen at random and assessed
      using four tools namely, self administered questionnaire : provision of
      adolescent friendly services; medical screening and focus group discussions.
      RESULTS: Seventy two percent girls and 56% boys reported health problems during
      survey with an average of 1.93 complaints per girl and 0.5 complaints per boy.
      However, only 43% girls and 35% boys reported to the clinic voluntarily to seek
      help and only one fifth the amount of problems were reported at the clinic in
      comparison to the quantum of problems reported in survey, which probably reflects
      a poor health seeking behaviour. A medical checkup with emphasis on assessment of
      reproductive health and nutritional status helped in detecting almost the same
      number of reproductive health problems as reported by them in survey. This
      intervention helped to increase the client attendance in subsequent period of
      next one year from 43% to 60% among girls and from 35% to 42% among boys.
      CONCLUSION: Our study shows that to increase help seeking behaviour of
      adolescents, apart from health and life skill education, their medical screening
      with a focus on reproductive health by trained physicians, parental involvement,
      supported by adolescent friendly centers (AFC) for counseling, referral and
      follow up are essential.

PMID- 16816514
TI  - Retinopathy of prematurity screening by non-retinologists.
AB  - OBJECTIVE: To detect the screening efficiency of general ophthalmologists
      (ophthalmic residents) as well as non-ophthalmologists (pediatric residents and
      nurses posted in neonatal intensive care unit) in screening (ROP) retinopathy of
      prematurity on the basis of posterior pole vascular changes. METHODS: Prospective
      consecutive review in a tertiary care hospital setting. Five groups (each
      comprising of one ophthalmic resident, one pediatric resident and a nurse)
      examined the posterior pole vessels of 200 eyes of ROP with a direct
      ophthalmoscope and compared with an ROP specialist using indirect ophthalmoscope.
      SPSS (Statistical Package for the Social Science), version 10.0 was used for the
      analysis. RESULTS: Ophthalmic residents findings were: (sensitivity 95.68%,
      specificity 92.85%, positive predictive value 94.81%, negative predictive value
      93.97%; pediatric residents findings were : (sensitivity 92.24%, specificity
      88.09%, positive predictive value 91.45%, negative predictive value 89.15%); and
      nurses, finding were: (sensitivity 88.79%, specificity 85.71%, positive
      predictive value 89.56%, and negative predictive value 84.70%). The results had
      no statistically significant difference in diagnostic reliability. Kappa
      agreement analysis was significant for ophthalmic residents (0.887), pediatric
      residents (0.805) and nurses (0.744) compared with the ROP specialist. None of
      the children diagnosed with pre-threshold or threshold ROP was thought to have
      normal posterior pole vessels by the trainees. CONCLUSIONS: Given adequate
      training, general ophthalmologists and non-ophthalmologists (pediatricians and
      nurse practitioners) are independently reliable in detecting posterior pole
      changes in ROP babies using direct ophthalmoscope and can be provided with a
      screening protocol.

PMID- 16816515
TI  - Cytomegalovirus infection in neonates following exchange transfusion.
AB  - OBJECTIVES: This study was undertaken to ascertain the acquisition of
      cytomegalovirus infection following exchange transfusion and factors affecting
      such transmission in newborn infants at a tertiary care hospital in India.
      METHODS: Neonates undergoing double volume exchange transfusion (for any
      indication) with whole blood in the Neonatal Intensive Care Unit were enrolled
      over a 8 month period. Serum samples from the infant were collected for CMV
      serology before exchange transfusion, and at 6 and 12 weeks following the
      exchange. CMV serology was also conducted on samples obtained from the respective
      maternal and donor blood. RESULTS: Of 47 neonates who received exchange
      transfusion during the study period; only 26 (55.3%) neonates were finally
      followed up till 12 weeks of age. Only 3 (11.5%) children demonstrated CMV
      seroconversion during follow-up; all were low birth weight and small for
      gestational age. None of them demonstrated any clinical, hematological,
      biochemical, or radiological signs suggestive of perinatal CMV infection either
      at birth or during the course of follow-up. CONCLUSION: Exchange transfusion in
      neonates can result in perinatal transmission of CMV infection in low birth
      weight neonates. Such transmission does not result in any immediate
      manifestations. Data are not sufficient to warrant routine CMV screening of donor
      blood for exchange transfusion in our setting.

PMID- 16816516
TI  - Superior mesentric artery compression syndrome.
AB  - Superior Mesenteric Artery Syndrome is an atypical cause of high intestinal
      obstruction seen frequently in patients with rapid weight loss or immobilization
      in a body cast (?also called CAST Syndrome). The SMA impinges on the third part
      of the duodenum immediately after originating from the anterior aspect of aorta,
      making an abnormally narrow angle with the later. Intestinal obstruction results
      causing characteristic symptoms like postprandial epigastric pain, eructations,
      fullness and vomiting. Here we report such a case of SMA syndrome in a patient
      with history of rapid loss of weight.

PMID- 16816517
TI  - Globe calcification in congenital toxoplasmosis.
AB  - Various patterns of distribution of intracerebral calcification have been
      described in congenital toxoplasmosis. We report a case of congenital
      toxoplasmosis with a rare finding of calcification in the globe detected by CT
      scan that has not been described earlier.

PMID- 16816518
TI  - Acute osteomyelitis in congenital hypofibrinogenemia.
AB  - A 10-month-old female child presented with intermittent high grade fever, pain
      and diffuse swelling in the left knee joint with history of ecchymosis in
      different areas of the body. There was radiological features of acute
      osteomyelitis, low fibrinogen level and bacteremia due to the presence of
      coagulase positive staphylococcus aureus. The child responded nicely to the
      treatment for acute osteomyelitis and congenital hypofibrinogenemia. So, in
      congenital hypofibrinogenemia, a joint swelling might be a resultant of an acute
      osteomyelitis, not mere hemarthrosis.

PMID- 16816519
TI  - Vincristine induced cranial polyneuropathy.
AB  - We describe a 5-year-old girl showed recovery of vincristine induced cranial
      polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl
      was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received
      chemotherapy according to the previously described modified St. Jude total
      therapy studies XIII. Five days after the fourth dose of vincristine, she
      presented with bilateral ptosis. Neurological examination revealed bilateral
      ptosis, and complete external opthalmoplegia with normal pupillary and corneal
      reflexes. She received 3.8 mg cumulative dose of vincristin before development of
      ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine
      and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7
      days of pyridoxine and pyridostigmine treatment and completely resolved after two
      weeks. The both agents were given for 3 weeks and were well tolerated without any
      side effects. During the follow up period we did not observe residue or
      recurrence of the ptosis.

PMID- 16816520
TI  - Pediatricians' views about oral health care.
AB  - Pediatricians and family practitioners have the responsibility of providing the
      crucial primary care for the children. They are considered to be in a unique
      position to contribute to the dental health of their young patients. In view of
      this a study was conducted in Mangalore city (India) to assess pediatricians'
      views about oral health care and their advice regarding oral hygiene maintenance.
      Fifty pediatricians were personally interviewed with a questionnaire. All
      pediatricians acknowledged their role in oral hygiene maintenance of their
      patients. This study showed that there is a need for more communication between
      the two pediatric specialties of medicine and dentistry so as to deliver better
      child health care.

PMID- 16816521
TI  - Proptosis in a young child.
AB  - We encountered an extremely unusual presentation of proptosis in a 7-yr-old boy
      due to psammomatoid juvenile ossifying fibroma of frontoethmoidal region. The
      tumor also led to development of mucocele in the frontal sinus not yet fully
      developed as on opposite side.

PMID- 16816522
TI  - Macroscopic T wave alternans in long QT syndrome.
AB  - A 6 year old girl was admitted with recurrent episodes of loss of consciousness.
      ECG showed prolonged QT interval and macroscopic T Wave alternans. Identification
      of this ECG pattern is important since it can lead to potentially lethal
      arrhythmias.

PMID- 16816523
TI  - A short boy with a limp.

PMID- 16816524
TI  - Vibrio cholerae 01 ogawa (Eltor) diarrhoea at Sevagram.

PMID- 16816525
TI  - Kawasaki disease is not rare in India.

PMID- 16816526
TI  - Oil that spoils the child.

PMID- 16816527
TI  - Kawasaki disease registries reap results experience in Mumbai.

PMID- 16816528
TI  - CFH gene variant, Y402H, and smoking, body mass index, environmental associations
      with advanced age-related macular degeneration.
AB  - OBJECTIVES: We tested the hypothesis that modifiable lifestyle factors alter the
      genetic susceptibility associated with a common coding variant in the complement
      factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly,
      age-related macular degeneration (AMD). METHODS: In this case-control association
      analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study
      with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated.
      AMD status was determined by grading of fundus photographs. Risk factors
      including cigarette smoking and body mass index (BMI) were assessed and DNA
      specimens were genotyped for the variant in the CFH gene. Unconditional logistic
      regression analyses were performed. Attributable risks and multivariable AMD risk
      scores were calculated. RESULTS: The number of risk alleles for Y402H was
      associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence
      interval (CI) 1.8-3.8) for the CT heterozygous genotype and OR 7.4 (4.7-11.8) for
      the homozygous CC risk genotype, after controlling for demographic and behavioral
      risk factors. Current cigarette smoking (OR 5.1) and high BMI > or =30 (OR 2.1)
      were independently related to AMD, controlling for genotype. The association
      between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the
      CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR
      10.2) conferred the greatest risks. Gene plus environment risk scores provided an
      area under the receiver operating characteristic (ROC) curve of 0.70-0.75.
      CONCLUSIONS: Genetic and environmental factors are independently related to
      advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk
      score identifies a highly susceptible population.

PMID- 16816529
TI  - Influence of daily consumption of probiotic and conventional yoghurt on the
      plasma lipid profile in young healthy women.
AB  - BACKGROUND: A number of studies have found conflicting results concerning the
      modulation of plasma lipids induced by probiotics. Therefore, the aim of this
      study was to verify and compare the effects of probiotic and conventional yoghurt
      on the plasma lipid profile of normocholesterolemic women. METHODS: In this
      study, female volunteers consumed 100 g/day of probiotic (n = 17) or conventional
      yoghurt (n = 16) for 2 weeks (T1-T2) and 200 g/day for further 2 weeks (T2-T3). A
      washout phase lasting 2 weeks followed (T4). Total and HDL cholesterol and
      triglycerides were determined by enzymatic methods; LDL cholesterol was
      calculated using the Friedewald formula. RESULTS: The average concentration of
      total cholesterol was consistent throughout the whole study in the control group,
      but decreased significantly (p < 0.01) in the probiotic group consuming 200 g
      yoghurt/day (T2-T3). During the period of daily yoghurt intake (T1-T3) the mean
      HDL cholesterol level increased significantly (p < 0.05) in the probiotic group,
      resulting in a significant (p < 0.05) improvement of the total/HDL cholesterol
      ratio. The significant (p < 0.01) reduction of the average plasma LDL cholesterol
      values found in this period (T1-T3) in the probiotic and the control groups was
      associated with a significant (p < 0.05) improvement of the LDL/HDL cholesterol
      ratios in both tested groups. CONCLUSION: Although several lipid parameters
      changed during the study in both the probiotic and the control group, no
      significant differences between the groups were observed. Therefore, it can be
      concluded that the regular consumption of both probiotic and conventional yoghurt
      for 4 weeks had a positive effect on the lipid profile in plasma of healthy
      women.

PMID- 16816530
TI  - Nutritional assessment: predictive variables at hospital admission related with
      length of stay.
AB  - BACKGROUND: Studies indicate that 40-50% of hospitalized patients show
      malnutrition, a variable that is associated with length of stay and morbidity.
      The aim of our study was to detect nutritional parameters, which could have an
      influence on length of stay in hospitalized patients. MATERIAL AND METHODS: All
      patients with a nutritional evaluation at hospital admission were elegible for
      inclusion. A total of 1,088 patients were studied from January 1999 to December
      2003. Length of stay (LOS) data was obtained from the patient hospital record
      after the patient was discharged. All patients received instruction in 24-hour
      written food record keeping. Albumin, prealbumin, transferrin, glucose levels and
      total lymphocytes, were measured in all patients. Weight, body mass index,
      tricipital skinfold, midarm muscle circumference and midarm muscle area were
      assessed in a standard way. Weight loss in the previous 3 months was recorded.
      RESULTS: A total of 1,088 patients were enrolled, mean age 61.8 +/- 17 years,
      weight 64.2 +/- 15 kg and BMI 23.9 +/- 4.6, with a weight loss 4.15 +/- 9.6 kg.
      The sex distribution of patients was 65.2% male and 34.8% females. Distribution
      of diagnosis showed leukemia and lymphoma (11.5%), solid cancer (37.4%),
      infections (3.5%), neurological disease (13.6%), respiratory tract disease
      (8.8%), and miscellaneous group (25.3%). Length of stay was 29.45 +/- 25.13 days.
      In whole group, the correlation analysis among length of stay (days) and
      predictive parameters showed a positive association between albumin and length of
      stay (r = -0.2; p < 0.05). In the multivariant analysis with a dependent variable
      (length of stay (days)) and independent variables with an association in
      univariant analysis adjusted by age and sex, only albumin remained as an
      independent predictor in the model (F = 8.8; p < 0.05), with an increase of 6.2
      days (95% CI: 3.5-8.9) with each decrease of 1 g/dl of albumin. CONCLUSION: The
      serum albumin levels are a good marker of LOS, a decrease in admission levels
      produces an increase in LOS.

PMID- 16816531
TI  - Reversible injury of internal capsule and splenium in a patient with transient
      hypoglycemic hemiparesis.

PMID- 16816532
TI  - Abducens nucleus syndrome due to pontine haemorrhage.

PMID- 16816533
TI  - Reduction in chronic allograft nephropathy by inhibition of p38 mitogen-activated
      protein kinase.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) is the major cause for late graft
      loss and is therefore a key target for therapy. METHODS: The impact of p38
      mitogen-activated kinase (MAPK) on CAN was investigated by administering FR167653
      (32 mg/kg/day), a specific inhibitor of p38 MAPK, for 4 weeks in addition to
      conventional cyclosporine therapy (1.5 mg/kg/day for 5 days) in an established
      experimental rat transplantation model. RESULTS: Transplanted rats develop
      glomerulosclerosis, arterial obliteration, interstitial fibrosis and tubular
      atrophy, all of which are characteristic of CAN, resulting in shortened survival
      on 32 weeks. However, the inhibition of p38 MAPK by daily subcutaneous treatment
      with FR167653 resulted in reduced CAN with preserved renal function and prolonged
      survival. The FR167653-treated rats had fewer phosphorylated p38 MAPK-positive
      cells in treated kidneys. Concomitantly, the expression of monocyte
      chemoattractant protein-1/CCL2 and transforming growth factor-beta(1) was
      markedly reduced. CONCLUSION: These results suggest that p38 MAPK phosphorylation
      is involved in the pathogenesis of CAN and provide evidence that p38 MAPK is a
      novel, appealing therapeutic target for combating CAN.

PMID- 16816534
TI  - Distribution of corticotropin-releasing factor and urocortin 1 in the vole brain.
AB  - Brain receptor patterns for the corticotropin-releasing factor (CRF) receptors,
      CRF1 and CRF2, are dramatically different between monogamous and promiscuous vole
      species, and CRF physiologically regulates pair bonding behavior in the
      monogamous prairie vole. However, it is uncertain whether species differences
      also exist in the neuroanatomical distribution of the endogenous ligands for the
      CRF1 and CRF2 receptors, such as CRF and urocortin-1 (Ucn1). We compared the
      expression of CRF and Ucn1 in four vole species, monogamous prairie and pine
      voles, and promiscuous meadow and montane voles, using in situ hybridization of
      CRF and Ucn1 mRNA. Our results reveal that CRF mRNA expression patterns in all
      four vole species appear highly conserved throughout the brain, including the
      olfactory bulb, nucleus accumbens, bed nucleus of the stria terminalis, medial
      preoptic area, central amygdala, hippocampus, posterior thalamus, and cerebellum.
      Similarly, Ucn1 mRNA primarily localized to the Edinger-Westphal nucleus in all
      four vole species. Immunocytochemistry in prairie and meadow voles confirmed
      localization of CRF and Ucn1 protein to these previously identified brain
      regions. These data demonstrate a striking dichotomy between the extraordinary
      species diversity of brain receptor patterns when compared to the highly
      conserved brain distributions of their respective ligands. Our findings generate
      novel hypotheses regarding the evolutionary mechanisms underlying the neural
      circuitry of species-typical social behaviors.

PMID- 16816535
TI  - Delayed closure of complex duodenal injuries by a Foley balloon catheter
      duodenostomy.
AB  - Less than 5% of abdominal injuries comprise the duodenum. Treatment is complex
      with high mortality and morbidity rates. These injuries are usually treated
      surgically and complications frequently occur. Three cases are presented in this
      communication in which the injury of the duodenum could not be repaired tension
      free. In these cases a Foley balloon catheter was used to close the rupture.
      After a few weeks, patients were fed through the Foley catheter duodenostomy
      until a fistular track was formed. On removal of the catheter the fistular track
      closed spontaneously including the perforation of the duodenum.

PMID- 16816536
TI  - Randomised trial comparing three different schedules of infusional 5FU and
      raltitrexed alone as first-line therapy in metastatic colorectal cancer. Final
      results of the Federation Francophone de Cancerologie Digestive (FFCD) 9601
      trial.
AB  - LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU)
      (AIO schedule) and raltitrexed have been demonstrated to be active agents in
      first-line treatment of colorectal cancer. We performed a 4-arm randomised trial
      to compare (1) a low-dose intravenous bolus of LV (20 mg/m2), followed by an
      intravenous bolus of 5FU (400 mg/m2), followed by a 22-hour continuous infusion
      of 5FU (600 mg/m2) on day 1 and day 2/2 weeks (ldLV5FU2 arm), (2) a weekly
      continuous infusion of high-dose 5FU (2.6 g/m2/week) for 6 weeks followed by a
      rest week (HD-FU arm) and (3) raltitrexed (Tomudex arm; 3 mg/m2/3 weeks) to
      standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were
      well balanced for sex ratio, age, WHO performance status, the primary tumour site
      and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two
      toxicity-related deaths were observed in the Tomudex arm. The treatments gave
      rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the
      patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively, p =
      0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was
      observed in 27, 25, 38 and 47% of the patients in the LV5FU2, ldLV5FU2, HD-FU and
      Tomudex arms, respectively (p = 0.016). An objective response was observed in 28,
      21, 22 and 10% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms,
      respectively (p = 0.04). Progression-free survival (PFS) of the patients in the
      Tomudex arm was statistically lower compared to that of patients treated with
      LV5FU2 or ldLV5FU2 (combined group; p = 0.013, log rank test). In conclusion,
      Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the
      early closure of the study and the lack of power of the comparison, it seems that
      ldLV5FU2 could be considered as an active, easier and less expensive option for
      the treatment of metastatic colorectal cancer compared to classic LV5FU2 or
      weekly HD-FU.

PMID- 16816537
TI  - Predicting development of infected necrosis in acute necrotizing pancreatitis.
AB  - The incidence of severe acute pancreatitis is about 30 cases per 100,000
      inhabitants, and it carries an overall mortality rate of 10-15%. Infection of
      pancreatic necrosis occurs in 20-30% of patients with severe acute pancreatitis
      and triples the mortality rate. Therefore, early prediction and diagnosis of
      infection in necrotizing pancreatitis are extremely important. The aim of the
      studies included in this review was to investigate the potential of specific
      prognostic factors to predict the development of secondary pancreatic infection
      in severe acute pancreatitis. This is seen as an important tool allowing to
      perform a computed tomography- or ultrasound-guided fine needle aspiration for
      bacteriological sampling at the right moment, to confirm the diagnosis, and,
      finally, to select the subgroup of patients who would benefit from the antibiotic
      prophylaxis. Precise patients' selection could possibly result in more rational
      use of antibiotics in patients with acute necrotizing pancreatitis and reduction
      of multi-resistant bacteria. Recent studies show that C-reactive protein is an
      important prognostic marker of pancreatic necrosis with the highest sensitivity
      and negative prognostic value in this respect. Procalcitonin alone or in
      combination with interleukin-6 best identifies patients not at risk for
      infection. However, a review of the clinical studies suggests that we still do
      not have an optimal model, thus there is a need for new more reliable biochemical
      and/or clinical predictive systems.

PMID- 16816538
TI  - QT dispersion and heart rate variability in sudden death risk stratification in
      patients with ischemic heart disease.
AB  - The aim of the article is to review the literature data about the significance
      and problems of the QT dispersion and heart rate variability in sudden death risk
      stratification in patients with coronary heart disease. QT dispersion is defined
      as the difference between the longest and the shortest QT intervals as measured
      in the 12-lead electrocardiogram. A direct relationship between the prolongation
      of QT dispersion and myocardial ischemia has been reported by several authors.
      Our previous study showed that QT dispersion assessed immediately after bicycle
      exercise test was significantly higher in patients with coronary stenoses of >
      50% as compared to the patients without coronary artery disease. Despite some
      controversial data, several studies showed that QT dispersion is a significant
      predictor of cardiovascular mortality. Heart rate variability representing a
      relationship between the autonomic nervous system and cardiovascular mortality,
      including sudden cardiac death, is one of the most promising markers. The
      predictive value of heart rate variability is independent of other factors
      established for postinfarction risk stratification, such as depressed left
      ventricular ejection fraction, increased ventricular ectopic activity, and
      presence of late potentials. For prediction of all-cause mortality, the value of
      heart rate variability is similar to that of left ventricular ejection fraction,
      but heart rate variability is superior to left ventricular ejection fraction in
      predicting arrhythmic events (sudden cardiac death and ventricular tachycardia).

PMID- 16816539
TI  - [Evaluation of diagnostic criteria for metabolic syndrome to identify insulin
      resistance].
AB  - The aim of study was to evaluate the possibilities of different diagnostic
      criteria for metabolic syndrome in identifying subjects with insulin resistance
      and to assess the prevalence of metabolic syndrome according to gender in one
      Lithuanian district. MATERIALS AND METHODS: A randomly selected sample of 1,115
      subjects aged 45-96 years (562 men and 553 women) was formed from general
      population of Raseiniai district. Insulin resistance was estimated using the
      homeostasis model assessment. Metabolic syndrome was determined according to the
      definitions of the World Health Organization, National Cholesterol Education
      Program Adults Treatment Panel III, and International Diabetes Federation.
      RESULTS: Using the World Health Organization criteria, metabolic syndrome was
      observed in 384 (34.4%) subjects (no difference between genders); according to
      the National Cholesterol Education Program--in 336 (30.1%) patients (in 107 men
      (19.0%) and 229 women (41.4%), p < 0.001); using International Diabetes
      Federation criteria--in 474 (42.5%) (175 men (31.1%) and 299 women (54.1%), p <
      0.001). Overall, 314 (28.5%) subjects were insulin resistant (no difference
      between genders). The highest prevalence of insulin resistance was determined in
      subjects with metabolic syndrome diagnosed according to the World Health
      Organization criteria--70.3% (n = 267), p < 0.05. Odds ratios to identify insulin
      resistant subjects with metabolic syndrome according to the World Health
      Organization criteria and the International Diabetes Federation criteria were
      22.4 and 2.3, respectively. CONCLUSIONS: The highest prevalence of metabolic
      syndrome was determined according to the International Diabetes Federation
      criteria. According to the National Cholesterol Education Program and
      International Diabetes Federation criteria metabolic syndrome was observed more
      frequently in women. The highest prevalence of insulin resistance was determined
      in metabolic syndrome group based on World Health Organization criteria. Using
      the World Health Organization and International Diabetes Federation criteria for
      metabolic syndrome provides more opportunities to identify subjects with insulin
      resistance.

PMID- 16816540
TI  - [Evaluation of systolic pressure in pulmonary artery by using impedance
      cardiography method].
AB  - OBJECTIVE: The methods of cardioechoscopy and heart catheterization are commonly
      used for diagnosis of pulmonary arterial hypertension in clinical practice. The
      aim of this study was to assess the diagnostic efficacy of impedance cardiography
      as safe, non-invasive, and cheap method for detection of pulmonary arterial
      hypertension. MATERIAL AND METHODS: Pulmonary artery systolic pressure was
      measured by impedance cardiography method in 109 patients: 41 patients with
      cardiovascular pathology when pulmonary arterial hypertension was determined by
      cardioechoscopy; 33 patients with cardiovascular pathology when using
      cardioechoscopy pulmonary arterial hypertension was not observed; 20 patients
      with pulmonary pathology when pulmonary arterial hypertension was determined by
      cardioechoscopy; 15 patients with pulmonary pathology when using cardioechoscopy
      pulmonary arterial hypertension was not observed. Cardioechoscopy results were
      compared with the results of impedance cardiography. RESULTS: We found a strong
      correlation between the data obtained by cardioechoscopy and impedance
      cardiography methods (r = 0.836, p = 0.0001). There was no statistically
      significant difference in the distributions of cardioechoscopy and impedance
      cardiography data (p = 0.915), and statistically significant difference was
      observed between the data of patients with pulmonary arterial hypertension and
      patients with normal pulmonary artery systolic pressure (p = 0.0001).
      CONCLUSIONS: After determining the correlation between cardioechoscopy and
      impedance cardiography methods (r = 0.836, p = 0.0001), computerized impedance
      cardiography should be considered as an informative method for diagnosis of
      pulmonary arterial hypertension.

PMID- 16816541
TI  - Changes in depression and quality of life during inpatient treatment of
      depression.
AB  - OBJECTIVE: The aim of the study was to evaluate the changes in the symptoms of
      depression and subjective quality of life improvement during inpatient treatment.
      MATERIAL AND METHODS: A total of 87 patients were assessed during the first five
      days of hospitalization and during naturalistic follow-up at the time of
      discharge using Composite International Diagnostic Interview Short Form (CIDI
      SF), structured interview for depressive symptoms assessment, and World Health
      Organization Quality of Life Abbreviated Questionnaire. RESULTS: Results indicate
      that symptoms of depression decrease and quality of life increases during
      inpatient treatment. However, high frequency of residual symptoms was observed.
      More than half of all patients reported ten or more symptoms at time of
      discharge. Although same gender differences in the frequency and severity of
      depressive symptoms were observed at time of admission, gender did not impact
      significantly treatment outcomes. Older age, comorbid somatic diseases, higher
      number of depressive symptoms at the time of admission, CIDI-SF confirmed major
      depressive episode, and lower quality of life were related to poor outcome of the
      treatment. Multiple regression analyses suggested that CIDI-SF confirmed major
      depressive episode and physical health domain of the quality of life were the
      most significant predictors of the outcome. CONCLUSION: Combination of measures
      of clinical assessment and quality of life can be useful for more complete
      patients' evaluation and the prediction of treatment outcome.

PMID- 16816542
TI  - Oxidative function of neutrophils in periodontitis patients with type 1 diabetes
      mellitus.
AB  - BACKGROUND: The involvement of reactive oxygen species in periodontal diseases is
      unclear. The aim of the present study was to explore the oxidative function of
      neutrophilic leukocytes of the peripheral venous blood in patients with severe
      periodontitis and type 1 diabetes mellitus and in the control subjects with
      healthy periodontal tissues and without systemic diseases. MATERIALS AND METHODS:
      The leukocytes for the present investigation were obtained from peripheral venous
      blood of 38 patients with severe periodontitis and type 1 diabetes mellitus and
      27 control subjects. The maximal luminol-dependent chemiluminescence and peak
      time values of neutrophils stimulated with non-opsonized Escherichia coli ATCC
      25922 and Staphylococcus aureus 256 were measured. RESULTS: The maximal luminol
      dependent chemiluminescence of neutrophils in patients with severe periodontitis,
      stimulated with non-opsonized Escherichia coli and Staphylococcus aureus, is
      mainly lower than that in the control group subjects (p < 0.001). Luminol
      dependent chemiluminescence of neutrophils reached its maximal value at the same
      time in both the diseased and the healthy patients. CONCLUSION: In periodontitis,
      local non-opsonized bacteria might stimulate neutrophilic leukocytes to release
      oxygen species. However, these cells in patients with periodontitis are
      characterized by a lower intensity of luminol-dependent chemiluminescence (p <
      0.001) compared to analogous findings in people with healthy periodontal tissues.
      This might indicate insufficient microbicidal activity of these cells in patients
      with periodontitis.

PMID- 16816543
TI  - Early and late reconstruction in brachial plexus palsy: a preliminary report.
AB  - OBJECTIVE: To evaluate the most effective surgical procedures in the early and
      late reconstruction of brachial plexus after its traumatic injury. MATERIAL AND
      METHODS: A total of 14 consecutive patients with brachial plexus injuries were
      examined and operated on at the Department of Plastic and Reconstructive Surgery
      and Burns at Kaunas University of Medicine Hospital. Less than half of them (43%)
      came for surgery in the early stage of disease--within 12 months after injury-
      and 57% in the late stage--1-15 years after trauma. Altogether, 23 operations-
      neurolysis, nerve transfer, tendon transfer, and arthrodesis--were performed.
      Patients were followed up for an average of 12.5 months (range 4 to 19 months)
      after surgery. Postoperative motor assessment of hand function was based on the
      motor classification M0-M6 of Mallet and British Medical Research Council Muscle
      grading system. Results were considered positive if the range of active movements
      increased no less than 5-10 degrees odependently from the level of injury and
      motor strength--no less than 1-2 grades (M0-->M2 or M2-->M3). RESULTS: Of the
      eight investigated, six patients from early group showed positive results. The
      most effective surgical procedures were neurolysis and nerve transfer. A
      significant improvement in the patients of late group was observed after tendon
      transfer procedure. Nevertheless, the recovery process of motor function was too
      slow or even minimal in 31% of patients to satisfy the patient and the surgeon.
      CONCLUSIONS: Neurolysis or nerve transfer in the early stage or tendon transfer
      in the late stage after brachial plexus injury may result in a significant
      improvement of motor function of the hand. Sharing the information concerning
      brachial plexus reconstruction with neonatologists, neuropathologists,
      traumatologists, and hand therapists would be helpful in operating such patients
      timely and treating them adequately after surgery.

PMID- 16816544
TI  - [Successful treatment of degenerative critical aortic stenosis at stage of
      valvular cardiomyopathy].
AB  - Degenerative aortic stenosis and mitral annulus calcification are the most common
      valvular abnormalities in elderly population. The incidence of these
      abnormalities has increased due to increased life expectancy. In recent years,
      new diagnostic techniques have improved the accuracy of diagnosis of valvular
      heart disease, however, cases of advanced critical aortic stenosis with valvular
      cardiomyopathy and severe heart failure still occur. A clinical case of critical
      degenerative aortic stenosis and mitral annulus calcinosis, mitral stenosis and
      regurgitation, subsequently significantly decreased ejection fraction (15%)
      accompanied by valvular cardiomyopathy and severe congestive heart failure is
      described. Ischemic heart disease was excluded. Cardiosurgery including
      implantation of aortic and mitral bioprosthesis and tricuspid annuloplasty was
      performed after intensive medical treatment and improvement of heart failure
      symptoms. After follow-up of six months, a 76-year-old female patient has just
      symptoms of mild left-ventricular dysfunction corresponding to New York Heart
      Association functional class II.

PMID- 16816545
TI  - [Selective apheresis of low-density lipoproteins].
AB  - The case of rare complicated homozygous hypercholesterolemia treated by a direct
      adsorption of lipoprotein apheresis procedure is presented in this article. In
      total eight sessions of direct adsorption of lipoprotein apheresis were performed
      on 14-year-old patient from June 2004 to January 2005. Blood flow rate was 30-50
      ml/min. Central or ulnar veins were punctured. Lipids levels before and after
      lipid apheresis were measured during each session throughout the study period.
      The mean decrease in low-density lipoprotein cholesterol levels was 34.3-52.6%
      compared to baseline, total cholesterol--26.4-49.1%, lipoprotein (a)--67.4 and
      90.9%, apolipoprotein B--26.4 and 48.4%. No side effects and complications were
      observed. The last four sessions were performed in a day unit.

PMID- 16816546
TI  - Application of Photoshop-based image analysis and TUNEL for the distribution and
      quantification of dexamethasone-induced apoptotic cells in rat thymus.
AB  - The aim of the present study was to determine the target site cells in the rat
      thymus after exposure to the synthetic glucocorticoid, dexamethasone, at
      therapeutic doses. The findings of histology and histochemistry (Feulgen,
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling--TUNEL)
      with quantification by computerized histomorphometry are described. MATERIAL AND
      METHODS: A quantified investigation of apoptotic and mitotic thymic lymphocytes
      in 36 young adult Wistar rats was performed at 1-7 days after a 3-day injection
      of dexamethasone (a total dose of 1.2 mg/rat intraperitoneally). RESULTS: At the
      first day after dexamethasone administration the moderate involution and atrophy
      of thymus histology were observed with simultaneous fall in cortical cellularity
      and mitotic activity of thymocytes. More rapid fall appeared in the inner cortex.
      The number of apoptotic (TUNEL-positive) cells was significantly increased. On
      the days 5 and 7 the expression of apoptosis and the cell proliferation were at
      almost normal level. CONCLUSIONS: The findings suggest that dexamethasone-induced
      apoptosis of cortical thymic lymphocytes, mainly correlated with synchronous
      inhibition of mitosis and cell number fall in thymus. The main target sites of
      dexamethasone injury were cells in the inner cortex of lobuli thymi.

PMID- 16816547
TI  - The effect of long-term swimming program on glycemia control in 14-19-year aged
      healthy girls and girls with type 1 diabetes mellitus.
AB  - The aim of this study was to evaluate the effect of long-term physical activity
      in the water on glucose control. MATERIAL AND METHODS: Altogether, 19 girls with
      duration of diabetes of 8.1 +/- 0.9 years and 28 healthy girls aged 14-19 years
      participated in the study. The participants with type 1 diabetes mellitus were
      questioned; glycosylated hemoglobin was measured before and after long-term
      swimming program for the participants with type 1 diabetes mellitus. Glycemia
      control was assessed by blood glucose monitoring before and after every physical
      sessions. Training sessions (each lasted for 45 min) were held twice per week for
      14 weeks. A total of 28 trainings were performed in the swimming pool. Workload
      intensity was corrected by pulse measurement before and after every session in
      the water. RESULTS: After a 14-week long-term physical program glycosylated
      hemoglobin level has decreased (p < 0.01) in diabetic subjects (8.5 +/- 0.4 vs
      7.8 +/- 0.3%). Hyperglycemia significantly decreased for all subjects, but its
      response to the physical exercises in the water was the highest in diabetics (p <
      0.001). CONCLUSION: Long-term physical activity program in the water improved
      glycemia control for all participants.

PMID- 16816548
TI  - [Ecstasy toxicity].
AB  - The substance, 3,4-methylenedioxymethamphetamine (MDMA) or ecstasy, is an
      amphetamine derivate. A mistaken belief that it is a safe drug of low toxicity
      and a long duration of action has led to its widespread popularity among
      teenagers and young adults in recent years. Unfortunately, ecstasy use has
      increased to epidemic proportions. In this review article pharmacokinetics and
      pathophysiology of MDMA, general medical adverse effects, cardiovascular effects,
      serotonin syndrome, hyponatremia, neurologic effects, hepatotoxicity, and long
      term neuropsychiatric effects, clinical features of toxicity, prehospital and
      emergency department care problems, and mortality/morbidity, prophylactic advices
      are discussed.

PMID- 16816549
TI  - HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell
      culture.
AB  - BACKGROUND: Genotypic diversity among HIV-1 subtypes and circulating recombinant
      forms (CRF) may lead to distinct pathways to drug resistance. This study
      evaluated subtype-related differences in the development of resistance in culture
      to tenofovir. METHODS: Genotyping determined nucleotide diversity among subtypes.
      Representative subtype B, C, CRF1_AE, CRF2_AG, G, and HIV-2 isolates were
      selected for resistance to tenofovir, lamivudine and didanosine in cell culture.
      Phenotypic assays determined the effects of the K65R substitution in reverse
      transcriptase (RT) on drug susceptibility. RESULTS: Subtype C isolates show
      unique polymorphisms in RT codons 64 (AAG-->AAA), 65 (AAA-->AAG), and 66 (AAA-
      >AAG), absent in other subtypes. The K65R mutation (AAG-->AGG) arose with
      tenofovir by week 12 in four subtype C selections. In contrast, no tenofovir
      resistance arose in four subtype B (> 34-74 weeks), one each of CRF2_AG and G (>
      30-33 weeks), and three HIV-2 (> 27-28 weeks) selections. K65R appeared after 55
      and 73 weeks in two CRF1_AE selections with tenofovir. In contrast, times to the
      appearance of M184V with lamivudine pressure (weeks 8-14) did not vary among
      subtypes. Selective didanosine pressure resulted in the appearance of M184V and
      L74V after 38 weeks in two of four subtype C selections. The K65R transitions in
      subtype C and other subtypes (AGG and AGA) conferred similar 6.5-10-fold
      resistance to tenofovir and five to 25-fold cross-resistance to each of abacavir,
      lamivudine, and didanosine, while not affecting zidovudine susceptibility.
      CONCLUSION: Tenofovir -based regimens will need to be carefully monitored in
      subtype C infections for the possible selection of K65R.

PMID- 16816550
TI  - Effectiveness of HIV prevention strategies in resource-poor countries: tailoring
      the intervention to the context.

PMID- 16816551
TI  - Ex vivo culture of human colorectal tissue for the evaluation of candidate
      microbicides.
AB  - OBJECTIVES: Establishment of an in vitro model to evaluate rectal safety and the
      efficacy of microbicide candidates. DESIGN: An investigation and characterization
      of human colorectal explant culture for screening candidate microbicides to
      prevent rectal transmission of HIV-1 infection. METHODS: Human colorectal
      explants were cultured at the liquid-air interface on gelfoam rafts. Phenotypic
      characterization of HIV-1 target cells was performed by fluorescence-activated
      cell sorter analysis. HIV-1 infection was determined by the measurement of p24
      antigen release, viral RNA, and proviral DNA accumulation. RESULTS: Colorectal
      explant CD4 T cells expressed higher CCR5 and CXCR4 levels compared with blood.
      Minor differences between the rectal and sigmoid colon were observed with a trend
      for slightly higher CCR5 and HLA-DR expression in cells from the sigmoid colon.
      Favourable culture conditions were established for colorectal tissue. Although
      tissue structure degenerated with time, CD4: CD8 cell ratios remained constant,
      and tissue supported productive HIV-1 infection. The ability of candidate
      microbicides to inhibit R5 HIV-1 infection was evaluated. Polyanion candidates,
      PRO2000 and dextrin sulphate, provided 99% protection at 1 microg/ml and 1 mg/ml,
      respectively, equivalent to 1/5000 and 1/40 of the vaginal formulations. The
      nucleotide reverse transcriptase inhibitor (NRTI) 9-[2
      (phosphonomethoxy)propyl]adenine (PMPA) provided protection at concentrations
      1000-fold lower (10 microg/ml) than the proposed vaginal formulation (1%).
      Furthermore, non-NRTI UC-781 and TMC-120 provided greater than 99% inhibition at
      3.3 or 0.33 microg/ml, respectively. No products demonstrated toxicity to rectal
      mucosa at inhibitory concentrations. CONCLUSION: Colorectal explant culture was
      shown to be a useful tool for the preclinical evaluation of potential
      microbicides. The data suggest that rectally applied microbicides might provide
      protection from HIV-1 transmission.

PMID- 16816552
TI  - Similar changes in plasmacytoid dendritic cell and CD4 T-cell counts during
      primary HIV-1 infection and treatment.
AB  - OBJECTIVES: Reduced dendritic cell (DC) frequencies and functions in individuals
      with longstanding HIV-1 infection are predictive of opportunistic infections and
      AIDS. To investigate possible early alterations in DC levels after HIV infection,
      we prospectively examined plasmacytoid dendritic cell (pDC) and myeloid dendritic
      cell (mDC) frequencies and plasma IFN-alpha levels in patients undergoing primary
      HIV-1 infection (PHI). METHODS: Peripheral blood DC frequencies and absolute
      counts were determined by flow cytometry. Plasma IFN-alpha levels were measured
      by enzyme-linked immunosorbent assay (ELISA). RESULTS: In comparison to
      uninfected subjects, pDC, but not mDC, levels were reduced (P < 0.001) in
      subjects with PHI, especially in those with high viral loads or low CD4 T-cell
      counts. During 24-48 weeks of observation, untreated subjects experienced slight
      declines in pDC and CD4 T-cell levels. In contrast, subjects initiating early
      antiretroviral therapy (ART) exhibited increases (P < 0.001) in pDC and CD4 T
      cell counts. No effect of treatment on mDC counts was observed. Circulating
      plasma IFN-alpha was undetectable by ELISA regardless of the duration of HIV-1
      infection. CONCLUSION: PHI is characterized by a reduction in pDC and CD4 T-cell
      counts that correlates with the magnitude of virus replication and is not
      evidenced by the mDC count or plasma IFN-alpha level. Early ART appears to have
      similar restorative effects on pDC and CD4 T-cell counts.

PMID- 16816553
TI  - Impact of occult hepatitis B virus infection in HIV patients naive for
      antiretroviral therapy.
AB  - OBJECTIVE: To study the impact of occult hepatitis B virus (HBV) infection in 115
      consecutive anti-HIV-positive, hepatitis B surface antigen-negative patients,
      naive for antiretroviral treatment. METHODS: Of these 115, 86 patients were
      followed for at least 6 months (range 6-36) with serial determinations of HIV RNA
      and HBV DNA by polymerase chain reaction and other laboratory tests. RESULTS: Of
      the 86 patients having a follow-up, plasma HBV DNA was detected in 17 (19.8%), 13
      on admission and four during follow-up. HBV DNA was more frequently found in
      patients with isolated anti-hepatitis B core (HBc; 35.5% of 31 cases) than in
      those lacking anti-HBc and anti-hepatitis B surface (8.8% of 41, P < 0.005), or
      showing both (21.4% of 14). Twenty-eight patients (32.5%) experienced a hepatic
      flare during the follow-up; this event was more frequent in the 17 HBV-DNA
      positive patients than in the 69 negative (64.7% versus 24.6%, P < 0.005). Of the
      13 HBV-DNA-positive patients on admission, 11 receiving HAART containing
      lamivudine became HBV-DNA negative, but two of these again became positive and
      experienced a hepatic flare during treatment and two both during and after
      lamivudine treatment. A hepatic flare also occurred under lamivudine treatment in
      two of the four patients in whom HBV DNA became detectable during follow-up. The
      role of immune reconstitution inflammatory syndrome and HAART in inducing a
      hepatic flare was found to be marginal in 49 patients with no HBV or hepatitis C
      virus marker. CONCLUSION: The study suggests that HBV occult infection,
      relatively frequent in anti-HIV-positive patients, is associated with hepatic
      flares.

PMID- 16816554
TI  - Efficacy and tolerability of 10-day monotherapy with apricitabine in
      antiretroviral-naive, HIV-infected patients.
AB  - OBJECTIVE: Apricitabine (formerly AVX754 and SPD754) is a deoxycytidine analogue
      nucleoside reverse transcriptase inhibitor in clinical development for patients
      with HIV disease. This study evaluated the antiretroviral efficacy, tolerability
      and safety of apricitabine monotherapy, administered for 10 days in
      antiretroviral-naive, HIV-1 infected adults. METHODS: Adult patients (> or = 18
      years) with HIV infection (CD4 count > or = 250 cells/microl; plasma HIV-1 RNA
      level 5000-100 000 copies/ml) were randomized to 10 days' double-blind oral
      therapy with placebo or apricitabine 400 mg/day, 800 mg/day, 1200 mg/day, or 1600
      mg/day. RESULTS: At 7 days, all apricitabine doses produced statistically
      significant log10 reductions in plasma HIV RNA levels from baseline relative to
      placebo (n = 13; P < 0.0001), as follows: -1.16 (400 mg; n = 11), -1.28 (800 mg;
      n = 12), -1.44 (1200 mg; n = 14), -1.30 (1600 mg; n = 13). After 10 days, the
      log10 viral load reductions with apricitabine 1200 mg (-1.65; P = 0.01) and 1600
      mg/day (-1.58; P = 0.04) were significantly greater than that with the 400-mg
      dose (-1.18). No clinically relevant changes were observed in CD4 or CD8 cell
      indices. Apricitabine was well tolerated and showed no tendency to select any
      particular resistance mutation. CONCLUSION: Apricitabine monotherapy showed
      promising antiretroviral efficacy, good tolerability and a low propensity for
      resistance selection in antiretroviral-naive HIV-infected patients treated for 10
      days. These results warrant further evaluation of the long-term clinical efficacy
      and tolerability of apricitabine.

PMID- 16816555
TI  - Abacavir hypersensitivity reaction in primary HIV infection.
AB  - OBJECTIVE: To evaluate risk factors associated with the abacavir hypersensitivity
      reaction during primary HIV infection (PHI). DESIGN: Acute HIV Infection and
      Early Disease Research Program protocol (AIEDRP) AI-02-001 provided
      antiretroviral therapy including abacavir. This retrospective analysis evaluated
      variables potentially associated with hypersensitivity in the cohort enrolled in
      AI-02-001 at the University of Washington Primary Infection Clinic. METHODS:
      Cases of suspected hypersensitivity were identified prospectively and reviewed
      retrospectively using a standardized case definition. Controls were the remaining
      cohort without hypersensitivity. Univariate analyses were performed by linear
      logistic regression. RESULTS: Nine (18%) of 50 individuals treated with abacavir
      developed suspected hypersensitivity. Two of nine cases and no controls were HLA
      B5701 positive. When antiretroviral medications were started, cases had lower
      mean CD8 T-cell percentage and plasma HIV RNA value. After 2 weeks on abacavir,
      cases had a lower mean HIV RNA value and a trend towards greater decrease in RNA.
      Cases began abacavir a median of 103 days after HIV acquisition compared to 48
      days for controls. There was no significant in vitro abacavir-specific
      lymphoproliferation or IFN-gamma production in peripheral blood mononuclear cells
      from individuals following the suspected hypersensitivity reaction. CONCLUSIONS:
      Abacavir use during PHI may be associated with increased risk of
      hypersensitivity. As in chronic infection, HLA-B5701 is associated with the
      abacavir hypersensitivity reaction in PHI. Although levels of CD8 T cells and HIV
      RNA may be risk factors for hypersensitivity, the observed association may be due
      to correlation with HLA-B5701. The interesting temporal association of
      hypersensitivity with initiation of abacavir later in PHI merits future
      investigation.

PMID- 16816556
TI  - Tuberculosis after HAART initiation in HIV-positive patients from five countries
      with a high tuberculosis burden.
AB  - BACKGROUND: HAART reduces tuberculosis (TB) incidence in people living with
      HIV/AIDS but those starting HAART may develop active TB or subclinical TB may
      become apparent in the immune reconstitution inflammatory syndrome. OBJECTIVE: To
      measure the incidence rate of notified TB in people receiving HAART in five HIV
      programmes occurring in low-resource countries with a high TB/HIV burden.
      METHODS: A retrospective review in five Medecins Sans Frontieres programmes
      (Cambodia, Thailand, Kenya, Malawi and Cameroon) allowed incidence rates of
      notified TB to be calculated based on follow-up time after HAART initiation.
      RESULT: Among 3151 patients analysed, 90% had a CD4 cell count of < 200
      cells/mul. Median follow-up time ranged from 3.7 months in Thailand or Kenya to
      11.1 months in Cambodia. Incidence rates were 7.6, 10.4, 17.6, 14.3 and 4.8/100
      person-years for pulmonary TB and 12.7, 4.3, 6.9, 2.1 and 0/100 person-years for
      extra-pulmonary TB in the programmes in Cambodia, Thailand, Kenya, Malawi and
      Cameroon, respectively. Overall, 62.3% of pulmonary TB and 54.9% of extra
      pulmonary TB were diagnosed within 3 months after HAART initiation. CONCLUSION:
      High incidence rates of notified TB under HAART in programmes held in poor
      resource countries were observed; these were likely to include both undiagnosed
      prevalent TB at HAART initiation and subclinical TB developing during the immune
      reconstitution inflammatory syndrome. This raises operational issues concerning
      TB diagnosis and treatment of TB/HIV-coinfected patients and prompts for urgent
      TB and HIV care integration.

PMID- 16816557
TI  - Maternal single-dose nevirapine versus placebo as part of an antiretroviral
      strategy to prevent mother-to-child HIV transmission in Botswana.
AB  - BACKGROUND: Single-dose nevirapine given to women and infants reduces mother-to
      child HIV transmission, but nevirapine resistance develops in a large percentage
      of women. OBJECTIVE: To determine whether the maternal nevirapine dose could be
      eliminated in the setting of zidovudine prophylaxis. DESIGN, SETTING, AND
      PARTICIPANTS: A 2 x 2 factorial, randomized, clinical trial, with a double
      blinded peripartum factor designed to assess the equivalence of maternal single
      dose nevirapine versus placebo with respect to HIV transmission. A total of 709
      HIV-infected pregnant women were randomized from four district hospitals in
      Botswana, resulting in 694 live first-born infants. HAART was available for women
      with AIDS. INTERVENTION: All women received a background of zidovudine from 34
      weeks' gestation through delivery, and all infants received single-dose
      nevirapine at birth and zidovudine from birth through 1 month. Women were
      randomized to receive either single-dose nevirapine or placebo during labor. MAIN
      OUTCOME MEASURES: The primary endpoint was infant HIV infection by the 1-month
      visit. RESULTS: Of the 694 infants in this equivalence study, 15 (4.3%) of 345 in
      the maternal nevirapine arm were HIV infected by 1 month, versus 13 (3.7%) of 349
      in the maternal placebo arm (95% confidence interval for difference, -2.4% to
      3.8%), meeting pre-determined equivalence criteria. Nevirapine resistance at 1
      month postpartum was detected in 45% of a random sample of women who received
      nevirapine. CONCLUSIONS: In the setting of maternal zidovudine and infant
      zidovudine plus single-dose nevirapine, infant HIV infection rates were similar
      whether women received single-dose nevirapine or placebo. This strategy avoids
      the potential for maternal nevirapine resistance.

PMID- 16816558
TI  - Predictive value of absolute CD4 cell count for disease progression in untreated
      HIV-1-infected children.
AB  - OBJECTIVES: To describe the relationship between absolute CD4 cell count and the
      short-term risk of disease progression in HIV-1-infected children. DESIGN: A meta
      analysis of individual longitudinal data on HIV-1-infected children enrolled in
      trials and cohort studies in Europe and the USA. METHODS: The risks of
      progression to death and AIDS (or death) within 12 months, in terms of age and
      the most recent CD4 cell count, were estimated using parametric survival models.
      The analysis was restricted to measurements before the start of antiretroviral
      therapy except zidovudine monotherapy. The values of the absolute CD4 cell count
      and percentage predicting selected levels of disease progression risk were
      determined from this and previous models. RESULTS: A total of 566 deaths was
      observed over 9128 person-years of follow-up, and 992 children progressed to AIDS
      or death over 7309 person-years of follow-up. In children older than 4 or 5
      years, the estimated risk of disease progression increased sharply when the CD4
      cell count fell below 200-300 cells/microl. As with other immunological markers,
      CD4 cell count was less prognostic in younger children. The CD4 cell count values
      predicting a 12-month risk of death of 2-5% and of AIDS of 5-10% were much more
      strongly influenced by age than equivalent CD4 cell percentage values.
      CONCLUSION: This study suggests it may be appropriate to extend CD4 cell count
      criteria for initiating antiretroviral therapy in HIV-1-infected adults to
      children as young as 4 or 5 years. Monitoring by CD4 cell count in younger
      children is problematical because age is a highly influential variable.

PMID- 16816559
TI  - Cognitive-behavioral intervention to enhance adherence to antiretroviral therapy:
      a randomized controlled trial (CCTG 578).
AB  - OBJECTIVE: We conducted a randomized, multi-site, controlled trial of a cognitive
      behavioral adherence intervention for patients initiating or changing an
      antiretroviral (ART) regimen. DESIGN: A 3 x 2 factorial design was used with the
      primary randomization assigning patients (1: 1: 1) to one of two adherence
      interventions or usual care. METHODS: The five-session adherence interventions
      consisted of cognitive-behavioral and motivational components, with or without a
      2-week pre-treatment placebo practice trial. Intent-to-treat analysis used
      probability weights and regression tree analysis to account for missing data.
      RESULTS: A total of 230 patients were randomized; 199 started ART, of whom 74%
      completed the 48-week study. Electronic monitored adherence outcomes between the
      two intervention groups did not differ significantly and were thus pooled in
      analyses. At week 4, 82% of intervention patients had taken at least 90% of their
      prescribed ART doses, compared with 65% of controls (P < 0.01); this group
      difference dropped to 12% at week 12 (72 versus 60%; P = 0.15) and 11% at week 24
      (66 versus 55%; P = 0.28). Mean adherence in the intervention group was
      significantly higher than the control group at week 24 (89 versus 81%; P < 0.05)
      only. There were no group differences with respect to HIV-1 RNA throughout the
      study. CONCLUSIONS: The effects of the cognitive-behavioral intervention on
      adherence were modest and transient, and no effects were observed on viral load
      or CD4 cell count. More robust effects may require a more intense intervention
      that combines ongoing adherence monitoring and individualized intervention
      "dosage" that matches the need and performance of each patient.

PMID- 16816560
TI  - Parenteral transmission during excision and treatment of tuberculosis and
      trypanosomiasis may be responsible for the HIV-2 epidemic in Guinea-Bissau.
AB  - BACKGROUND AND OBJECTIVE: The factors that led to the simultaneous emergence,
      decades ago, of HIV-1 in central Africa and HIV-2 in West Africa remain unclear.
      The low HIV-2-associated mortality enables epidemiological assessment of risk
      factors potentially relevant in the early stages of the epidemic. In Guinea
      Bissau, its epicentre, HIV-2 became highly prevalent (approximately 15%) in
      cohorts of individuals born before 1962, but is now disappearing whereas HIV-1
      prevalence is increasing. We sought to verify the hypothesis that parenteral
      transmission was the key factor in the building-up of the HIV-2 epidemic. DESIGN:
      Cross-sectional community survey of 1608 individuals aged > or = 50 years in
      Bissau. METHODS: Capillary blood was obtained for HIV serology. Associations
      between HIV-2 (alone or in dual HIV-1/HIV-2 infections) and exposures were
      measured with crude and adjusted odds ratios (AOR) and 95% confidence intervals
      (CI). RESULTS: Prevalence of HIV-2 was higher in women (160/1063; 15.1%) than men
      (45/545; 8.3%, P < 0.001). Among women, excision (AOR, 1.54; 95% CI, 1.08-2.18)
      was independently associated with HIV-2, as were age and being widowed (AOR,
      1.88; 95% CI, 1.29-2.74). Among men, HIV-2 was not associated with sexually
      transmitted infections or transactional sex. In an analysis comprising men and
      women that was adjusted for age, sex, ethnic group and marital status, HIV-2 was
      associated with having received injections for the treatment of tuberculosis
      (AOR, 2.12; 95% CI, 1.11-4.05) or trypanosomiasis (AOR, 1.75; 95% CI, 1.03-2.97).
      CONCLUSIONS: Parenteral transmission through ritual excision and multiple
      injections during treatment of tuberculosis and trypanosomiasis contributed to
      the emergence of HIV-2 in Guinea-Bissau.

PMID- 16816561
TI  - A phase III clinical trial of antibiotics to reduce chorioamnionitis-related
      perinatal HIV-1 transmission.
AB  - OBJECTIVE: A multisite study was conducted in Africa to assess the efficacy of
      antibiotics to reduce mother-to-child transmission (MTCT) of HIV-1. DESIGN: A
      randomized, double-blinded, placebo-controlled, phase III clinical trial.
      METHODS: HIV-1-infected women were randomly assigned at 20-24 weeks' gestation to
      receive either antibiotics (metronidazole plus erythromycin antenatally and
      metronidazole plus ampicillin intrapartum) or placebo. Maternal study procedures
      were performed at 20-24, 26-30, and 36 weeks antenatally, and at labor/delivery.
      Infants were seen at birth, 4-6 weeks, and 3, 6, 9 and 12 months. The primary
      efficacy endpoints were overall infant HIV-1 infection and HIV-1-free survival at
      4-6 weeks. All women and infants received single-dose nevirapine prophylaxis in
      this study. RESULTS: A total of 1510 live-born infants were included in the
      primary analysis. The proportions of HIV-1-infected infants at birth were similar
      (antibiotics 7.1%; placebo 8.3%; P = 0.41). Likewise, there were no statistically
      significant differences at 4-6 weeks in the overall risk of MTCT of HIV-1
      (antibiotics 16.2%; placebo 15.8%; P = 0.89) or HIV-1-free survival (79.4% in
      each study arm). Post-randomization, the proportion of women with bacterial
      vaginosis at the second antenatal visit was significantly lower in the
      antibiotics arm compared with the placebo arm (23.8 versus 39.7%; P < 0.001), but
      the frequency of histological chorioamnionitis was not different (antibiotics
      36.9%; placebo 39.7%; P = 0.30). Adverse events in mothers and their infants did
      not differ by randomization arm. CONCLUSION: This simple antepartum and
      peripartum antibiotic regimen did not reduce the risk of MTCT of HIV-1.

PMID- 16816562
TI  - Tuberculosis: the elephant in the AIDS clinic?

PMID- 16816563
TI  - Presence of numerous stop codons in HIV-1 reverse transcriptase proviral DNA
      sequences from patients with virological response to HAART.
AB  - The impact of proviral DNA reverse transcriptase mutations on virological failure
      was evaluated in 50 HIV-1 HAART-treated patients switching from a protease
      inhibitor to a non-nucleoside reverse transcriptase inhibitor. Neither the
      M184I/V mutation detected in 12 patients nor stop codons at tryptophane positions
      detected in 13 patients were associated with virological failure. Stop codons
      appeared under successful therapy in 12 patients. Their presence should be
      assessed in studies with higher statistical power.

PMID- 16816564
TI  - Detection of mycobacterial antigen responses in lung but not blood in HIV
      tuberculosis co-infected subjects.
AB  - Forty-seven HIV-infected adults had broncho-alveolar lavage stimulated with
      purified protein derivate of Mycobacterium tuberculosis. Eighteen of 19 (95%)
      with tuberculosis co-infection had interferon-gamma synthetic CD4 lymphocyte
      responses > 1% versus three of 28 (11%) without (P < 0.0001). Lung response was
      unrelated to blood CD4 cell count. BAL HIV tuberculosis responses were similar in
      25 HIV-uninfected tuberculosis patients. Responses in matched blood samples were
      often undetectable. Therefore, immunological tuberculosis assays seem less
      affected by HIV co-infection when lung-based.

PMID- 16816565
TI  - How well do trends in HIV prevalence in young people reflect HIV incidence?
      Results from 10 years of HIV serosurveillance in San Francisco.
AB  - Trends in HIV prevalence among young populations (15-24 years) are held to
      approximate trends in HIV incidence. Using the Serological Testing Algorithm for
      Recent HIV Seroconversion (STARHS) to estimate HIV incidence, we were able to
      demonstrate that this assumption was true for young patients at San Francisco's
      public sexually transmitted infection clinic from 1989 to 1998. However, the
      trend in prevalence among young people did not mirror trends in incidence in the
      overall population.

PMID- 16816566
TI  - Out-of-pocket costs of HAART limit HIV treatment responses in Botswana's private
      sector.
AB  - A large number of HIV-infected patients in sub-Saharan Africa pay out-of-pocket
      for HAART. This analysis from Botswana indicates that higher median out-of-pocket
      regimen costs to patients for the initial 30 days of HAART are associated with
      failure to achieve a viral load< 400 copies/ml [US$32; interquartile range (IQR),
      20-84 compared with US$22; (IQR, 17-36), P = 0.001]. HAART costs should be
      minimized as scale-up efforts in sub-Saharan Africa progress.

PMID- 16816567
TI  - Drug-resistance mutations can be archived very early in HIV primary infection.

PMID- 16816568
TI  - Compartment-specific HIV-1 resting T-cell reservoirs.

PMID- 16816569
TI  - Spontaneous HIV-1 replication in a B-lymphoblastoid cell line obtained from an
      HIV-1-positive patient with undetectable plasma viral load.

PMID- 16816570
TI  - Progressive multifocal leukoencephalopathy in HIV-2-infected patient.

PMID- 16816571
TI  - HIV therapy, hepatitis C virus infection, antibiotics and obesity, a mitochondria
      killer mix?

PMID- 16816572
TI  - Generic screening test for HIV infection.

PMID- 16816573
TI  - Is vaginal washing associated with increased risk of HIV-1 acquisition?

PMID- 16816575
TI  - A urine-based approach to scale up HIV testing in drug users.

PMID- 16816576
TI  - May immunization strategies that target dendritic cells really offer advantages
      for HIV-1?

PMID- 16816577
TI  - A case of voluntary intoxication with efavirenz and lamivudine.

PMID- 16816578
TI  - Will ART rollout in Africa drive an epidemic of drug resistant HIV?

PMID- 16816580
TI  - Shaping up to the future of shadows and spin.

PMID- 16816581
TI  - Prospective performance evaluation of emergency medical services for cardiac
      arrest in Lombardia: is something moving forward?
AB  - BACKGROUND: Limited data are available in our region on out-of-hospital treatment
      of cardiac arrest. The aim of this study is to evaluate whether the changes
      implemented in the emergency system (i.e. an increased number of basic life
      support and advance life support crews that were dispatched) produced the
      expected outcome improvements. METHODS: (a) EXPERIMENTAL DESIGN: data were
      prospectively collected on patients with sudden out-of-hospital cardiac arrest in
      three emergency dispatch centers for 3 months during two study periods, year 2000
      and year 2003, differentiated only by the increase of qualified crews. Outcomes
      and survival were evaluated at 24 h and 1 month after the event. (b) SETTING: out
      of-hospital treatment. (c) PATIENTS: 352 (174 in the second study period)
      patients suffering cardiac arrest. (d) INTERVENTIONS: the study was
      observational. RESULTS: We could document, between the two study periods, stable
      24 h (12.6 vs 9.1%) and 1 month survival (3.4 vs 5.8%, NS). Nevertheless, arrival
      time on site was significantly higher in the second period (from 8.3+/-3.3 to
      10.1+/-5.4 min, P<0.05). CONCLUSIONS: The strengthening of only one link of the
      chain-of-survival did not improve 1 month survival.

PMID- 16816582
TI  - The first Italian trauma registry of national relevance: methodology and initial
      results.
AB  - OBJECTIVE: To describe and discuss the ongoing endeavor to establish a
      multiregional trauma registry in Italy. METHODS:  DESIGN: Prospective
      observational analysis by description and cohort comparison. SETTING: Three
      Italian hospitals, referral centers for severely traumatized patients. PATIENTS:
      trauma victims admitted between 1 July 2004 and 28 February 2005 with an Injury
      Severity Score >15 or requiring early admission to intensive care. INTERVENTIONS:
      None. MEASURES: Compilation rates for some 'sentry' variables. Total number of
      patients and Injury Severity Score. Ten widely used descriptive variables (type
      of trauma, mechanism of injury, age, gender, Injury Severity Score, Revised
      Trauma Score, Prognostic Severity Index, 'call-to-hospital' and 'admission-to
      ward' intervals, and outcome at 30 days) measured in the subgroup with Injury
      Severity Score>15, in general and by hospital. RESULTS: A trauma registry has
      been established that fit the present organization of trauma care in Italy. It
      seems to compare well with the references available in the literature. Five
      hundred and forty-nine patients have been enrolled so far. The compilation rate
      has been well above 70% for all variables in all hospitals, except pre-hospital
      times in two hospitals. A substantial homogeneity exists among the hospitals in
      the general characteristics of the patients with Injury Severity Score>15.
      CONCLUSIONS: The project has achieved its goals so far. The previous estimates on
      the number of cases (about 300/year/hospital) are confirmed and major
      shortcomings in methodology seem unlikely. Therefore, positive future
      developments are possible: usage for quality improvement and research, linkage to
      other European registries and participation of other hospitals.

PMID- 16816583
TI  - The impact of a temporary ice-rink on an emergency department service.
AB  - BACKGROUND: A temporary ice-rink opened close to Cork city for 6 weeks from 30
      November 2003. During this time, a number of patients presented to the local
      emergency departments with ice-skating-related injuries. We documented these
      injuries. METHODS: All patients presenting to emergency departments in Cork city
      with ice-skating-related complaints were included. Information on age and sex,
      mechanism of injury, diagnosis, follow-up/disposition and ambulance service
      utilization was recorded. RESULTS: One hundred and twenty-five ice-rink-related
      attendances were reported at Cork emergency departments, representing 1.25% of
      total attendances. One hundred and twenty-three patients presented with skating
      related injuries and two with medical complaints occurring at the ice-rink: 70.8%
      were female patients and 29.2% were male patients. In the 4-14-year age group,
      however, 48.5% were girls and 51.5% were boys. Most injuries were directly due to
      falls; 5.6% were due to skate blades. The commonest site of injury was the upper
      limb. Fractures and dislocations accounted for 53.9% of injuries, with 20.5% of
      these requiring orthopaedic admission. Lacerations and digital injuries accounted
      for 7.1%, with 11% of these required admission for surgery. One minor head injury
      was reported. 38.1% had soft tissue injuries. Fifteen patients were transported
      by ambulance. These attendances represented a minimum overall cost of 77,510 euro
      to the local health service. CONCLUSIONS: A temporary ice-rink had a significant
      impact on local emergency departments. Currently, there is no specific
      legislation in Ireland relating to public health and safety in ice-rinks. We
      recommend consultation with local public bodies before opening such facilities,
      and appropriate regulation.

PMID- 16816584
TI  - Trends in the incidence and significance of presentations to the emergency
      department due to acute pancreatitis.
AB  - INTRODUCTION: Acute pancreatitis is an important cause of abdominal pain that may
      be associated with significant morbidity for the patient and considerable
      workload for the hospital. Our impression has been that it is becoming
      increasingly common, perhaps in tandem with increased rates of other alcohol
      related disease. METHODS: The medical records of all patients attending our
      emergency department with acute pancreatitis by Hospital Inpatient Enquiry coding
      over a 9-year period were examined to determine its incidence, aetiology and
      significance (Imrie severity of pancreatitis scoring, length of hospital stay and
      interventional workload). RESULTS: The incidence of acute pancreatitis (n=97, 40
      male patients) increased approximately threefold over the study period
      (especially in the lattermost triennial period with 75 patients) in a fashion
      disproportionate to changes in our locality's population. Gallstone-related
      disease continues to be most prevalent although alcohol-related disease also
      became more common. Disease severity (length of hospital stay and Imrie score)
      was similar throughout with a mean length of hospital stay exceeding that of the
      majority of accident and emergency admissions. Seven acute complications of acute
      pancreatitis were noted while 34 chronic sequelae developed. Requirement for
      invasive intervention doubled (n=19 in first triennial period in the study vs 39
      in the latter triennial period), although the relative need for endoscopic
      retrograde cholangiopancreaticography diminished with increased availability of
      magnetic resonance cholangiography imaging. Nine patients with gallstone-related
      acute pancreatitis suffered recurrent attacks while awaiting cholecystectomy.
      CONCLUSION: Acute pancreatitis is an increasingly frequent cause of hospital
      admission while the clinical significance of each incident remains high. The
      presentation of acute pancreatitis to the emergency department as an early
      declaration of symptomatic cholelithiasis is especially worrisome as it suggests
      a failing of recognition and/or effective referral of premonitory biliary
      complaints.

PMID- 16816585
TI  - Analysis of factors affecting emergency physicians' decisions in the management
      of chest pain patients.
AB  - OBJECTIVE: The aim of this study was to determine the factors most affecting
      emergency physicians' decisions in the management of chest pain patients.
      METHODS: This prospective randomized cross-sectional study was carried out
      between March 2004 and September 2004 in an urban university hospital emergency
      department. Residents collected data on patients' demographic features, chest
      pain characteristics, electrocardiography, cardiac enzymes and outcome of
      patients. RESULTS: Five hundred and sixty-two patients were enrolled in the
      study; 389 (69.2%) patients were classified as having cardiac chest pain. Of the
      389 patients suggested to have cardiac chest pain, 369 (94.4%) were classified as
      probable acute coronary syndrome; 286 (50.9%) patients were seen by cardiologists
      and 187 (33.3%) were admitted to the cardiology ward. The logistic regression
      analysis revealed that angina equivalents (P<0.001), age (P=0.002), history of
      coronary artery disease (P=0.003), electrocardiography (P=0.001), substernal
      chest pain (P=0.001), typical chest pain (P=0.000) and radiation of chest pain
      (P=0.039) were independent factors affecting emergency physicians' decisions.
      CONCLUSION: The factors affecting emergency physicians' decisions are correlated
      with guidelines.

PMID- 16816586
TI  - Pain in an emergency department: an audit.
AB  - OBJECTIVE: To evaluate the quality of care in patients with pain who visit the
      emergency department of a university hospital and the evolution of their pain
      during their emergency department stay. METHODS: A cross-sectional survey was
      performed using two valid scales (a numerical descriptor scale or a verbal pain
      intensity scale), and a structured questionnaire to patients and use of patient
      charts to collect information on pain intensity on arrival and before discharge,
      characteristics of pain and of its management. RESULTS: In the 726 participating
      patients, median age was 37 years (range: 18-97), and 54% of the patients were
      men. Upon arrival, 563 patients presented with pain (78%), rated > or =7 in 35%
      of the 390 patients evaluated using numerical descriptor scale. Forty-four
      percent had taken analgesics before arrival. Their median waiting time before
      initial medical examination was 30 min. Pain was identified by triage nurses
      (70%) or by physicians (77%) and was rated by nurses (23%) and physicians (11%).
      Forty-seven percent also experienced pain during care and 27% received analgesics
      during their stay. Pain intensity remained unchanged in 70% of patients,
      increased in 7% and decreased in 23%. Of the 480 patients with pain on arrival
      evaluated before discharge, 395 (82%) patients were unrelieved before going home,
      rated > or =7 in 32% of the 390 patients evaluated using numerical descriptor
      scale. Analgesics were ordered before leaving the emergency department in 81%.
      CONCLUSION: Even if pain has been identified, its assessment and management
      remains inadequate. The quality of care may be improved by educating the
      personnel in developing protocols and in evaluating pain management.

PMID- 16816587
TI  - Initial symptoms in pulmonary embolism differ from those in pneumonia: a
      retrospective study during seven years.
AB  - OBJECTIVE: To compare initial symptoms in pulmonary embolism with community
      acquired pneumonia and relate to C-reactive protein and pulmonary infiltrates in
      order to improve the clinical assessment at the emergency department. METHODS: A
      retrospective review of patients with pulmonary embolism diagnosed in the clinic
      for infectious diseases (CID), (n=25), and a randomized sample of patients with
      pulmonary embolism diagnosed in the department of medicine (n=64), and a
      randomized sample of patients with community-acquired pneumonia (n=54) diagnosed
      in the clinic for infectious diseases. RESULTS: Initial symptoms in pulmonary
      embolism, dominated by dyspnoea and/or pleuritic chest pain were significantly
      different from those in community-acquired pneumonia, dominated by fever, chills
      and/or cough (P<0.001). On admission, C-reactive protein and body temperature
      were significantly higher and pulmonary infiltrates were more common in pneumonia
      compared with randomized pulmonary embolism patients. Twenty-five patients with a
      final diagnosis of pulmonary embolism were erroneously suspected of having lung
      infection, owing to increased C-reactive protein, presence of pulmonary
      infiltrates and/or high fever. However, they had classical symptoms of pulmonary
      embolism. CONCLUSIONS: Pulmonary infiltrates, high fever and a high level of C
      reactive protein can deceive the physician to suspect pneumonia instead of
      pulmonary embolism. Classical initial symptoms ought to direct the physician in
      diagnosing pulmonary embolism. We emphasize a detailed patient history of initial
      symptoms.

PMID- 16816588
TI  - Patent foramen ovale as lifesaving purging valve.
AB  - Patent foramen ovale is considered as a potential risk factor for stroke owing to
      paradoxic embolism, leading to the question "to close or not to close the patent
      foramen ovale". We report a 26-year-old woman with chest pain, dyspnoea, sudden
      severe pain in both legs and paraplegia. Thoracic and abdominal computed
      tomography revealed massive pulmonary embolism and complete obstruction of the
      abdominal aorta. Interventional removal of the aortic thrombus was undertaken
      using the Fogarty catheter technique via the femoral arterial approach. As a
      result of worsening of cardiopulmonary function during the procedure, additional
      local thrombolysis, with a total of 50 mg recombinant tissue plasminogen
      activator, and fragmentation of the thrombus in the right pulmonary artery were
      performed via a femoral vein approach. Ultrasound studies revealed a patent
      foramen ovale of about 12 mm diameter with a significant right to left shunt.
      Under favourable conditions, a patent foramen ovale may allow the escape of a
      thrombus, sufficient to cause a potentially fatal pulmonary embolism, into the
      arterial system, where it can be removed by interventional manoeuvres.

PMID- 16816589
TI  - Nerve injury following shoulder dislocation: the emergency physician's
      perspective.
AB  - We describe the case of a 57-year-old woman who presented to the emergency
      department with a right anterior shoulder dislocation following a fall onto the
      right shoulder and right upper arm. She also complained of numbness in the right
      forearm and dorsum of the right hand. The examination revealed a bruise to the
      upper aspect of the right arm resulting from the impact following the fall. The
      patient also had a right wrist drop and loss of sensation in the lateral border
      of the right forearm and on the dorsum of the right hand, suggesting a radial
      nerve injury. She also had altered sensation in the ulnar distribution of her
      right hand, suspicious of concomitant ulnar nerve injury. No loss of sensation in
      the distribution of the axillary nerve (regimental patch) was observed. These
      findings were carefully documented and the patient subsequently had the shoulder
      reduced under entonox and morphine. The neurological deficits remained unchanged.
      The patient was sent home from the emergency room with arrangements for
      orthopaedic and physiotherapy follow-up. After a 3-month period, she had clinical
      and electromyography evidence of persistent radial and ulnar nerve deficit. She
      continues to have physiotherapy. This case highlights the need for awareness of
      the potential for nerve damage following shoulder dislocation and also to ensure
      that appropriate follow-up plan is instituted on discharge from the emergency
      department.

PMID- 16816590
TI  - Mountainbiker's hematuria: a case report.
AB  - Although exercise-induced hematuria is a well known finding in long distance
      running, it is extremely rare in cycling. We describe a case of gross atraumatic
      hematuria after mountainbiking. The only pathologic finding in our patient was a
      small hyperemic zone in the bladder mucosa suggesting a local traumatic origin
      due to repeated contact of the flaccid bladder wall against the bladder base.
      This in contrast with the renal origin commonly seen in marathon runners. It is a
      benign hematuria that usually resolves within a day without specific treatment.
      The best treatment is prevention by means of good bladder filling. Neoplasm of
      the urothelium should be ruled out in differential diagnosis.

PMID- 16816591
TI  - Cardial gunshot injury: treatment in a trauma hospital without a cardiac unit.
AB  - Gunshot injuries to the chest often require urgent admission to the nearest
      hospital, because of the cardiorespiratory status, transfer to a hospital without
      a cardiothoracic unit might be unsafe. In this case, a male patient was
      transferred to the nearest hospital on being shot through the heart. On
      admission, he was in shock, and immediate surgery was performed. We report our
      treatment regime for thoracic injuries and the specific management of this
      patient. We conclude that every hospital with an accident and emergency
      department has to be prepared for such an injury and that operative management is
      possible without cardiopulmonary bypass.

PMID- 16816592
TI  - Rickets in an adolescent girl.
AB  - The authors present a case of rickets in an adolescent girl who presented to the
      emergency department with bone pain. Emergency department staff should be aware
      that rickets is not just a disease of early childhood.

PMID- 16816593
TI  - Ureteral injury due to blunt abdominal trauma.
AB  - Ureteral injury is usually due to abdominal penetrating trauma or surgical
      insult. It has seldom been reported in patients with blunt abdominal trauma. A 20
      year-old man presented with left flank and inguinal area pain after blunt
      abdominal trauma sustained in a motor scooter accident. Acute hydronephrosis and
      hematuria were noted. Retrograde pyelography and ureteroscopic examination
      revealed left distal ureter edema with obstruction. The hydronephrosis resolved
      after temporary double-J-stenting.

PMID- 16816594
TI  - Nicotine gum withdrawal and migraine headaches.
AB  - Some abstinent smokers develop withdrawal symptoms when they stop using nicotine
      gum or when placebo is substituted. The present report describes a patient who
      suffered from severe migraine headaches after sudden discontinuation of nicotine
      gum. It has been suggested that physical dependence may be a cause of behavioral
      dependence on nicotine gum. Physicians should emphasize the need for gradual
      reduction of nicotine gum.

PMID- 16816595
TI  - Neurological emergencies as causes of accidents.

PMID- 16816597
TI  - Translating research into evidence-based nursing practice and evaluating
      effectiveness.

PMID- 16816598
TI  - Nurses and the Joint Commission unannounced survey process.

PMID- 16816599
TI  - The road to Magnet: one magnificent journey.

PMID- 16816600
TI  - Developing measures of pediatric nursing quality.
AB  - Recent research has highlighted the impact of nursing care on patient outcomes.
      The link to staffing has also been documented for selected conditions. To date,
      efforts to establish nurse-sensitive measures have focused largely on adults.
      This article describes the project undertaken to select and pilot 2 pediatric
      indicators of nursing quality care to be included in an ongoing national
      benchmarking program.

PMID- 16816602
TI  - The safety culture in a children's hospital.
AB  - Efforts to improve patient safety require an understanding of organizational
      culture. In a survey of inpatient healthcare providers in a children's hospital,
      physician perceptions of teamwork were higher than those of all other staff (P <
      .001). Recognition of the impact of stress and fatigue was low, and job
      satisfaction was high for all groups. A majority of respondents did not feel
      rewarded for incident reporting. Information on hospital-level safety culture can
      lead to targeted system improvement.

PMID- 16816603
TI  - Special Premie Oxygen Targeting (SPOT): a program to decrease the incidence of
      blindness in infants with retinopathy of prematurity.
AB  - Infants born prematurely have a plethora of medical problems. Some have cerebral
      palsy, resulting in limited mobility, while others require oxygen, hearing aids,
      and/or glasses for medical problems. Most of these could have been prevented if
      preterm birth was avoided, but efforts to curb this have been slow. This article
      discusses how blindness can be prevented in infants born prematurely by accepting
      lower oxygen saturations when on oxygen in the intensive care nursery.

PMID- 16816604
TI  - Partnering with patients and families in designing visual cues to prevent falls
      in hospitalized elders.
AB  - Prevention of falls in hospitalized elderly is critical to avoid injury and
      maintain independence. As part of a comprehensive program, nursing staff in a
      medical telemetry unit partnered with patients and their families to design and
      implement an educational poster to prevent falls. Ongoing patient/family feedback
      was used to modify the poster until it was appealing and effective for patients.
      The effort resulted in a marked decrease in falls on the unit over the pilot
      period.

PMID- 16816605
TI  - Evaluation of NOC standardized outcome of "health seeking behavior" in nurse
      managed clinics.
AB  - This study evaluated the accomplishment of the Nursing Outcomes Classification
      (NOC) outcome "Health Seeking Behavior" in 5 nurse-managed clinics. Nurse
      practitioners and registered nurses rated patients on 11 indicators of health
      seeking behaviors, and recorded their level of knowledge of the patient. A total
      of 556 evaluations were collected. Health seeking behavior scores were lowest in
      a rural county school-based clinic and highest in a federally qualified health
      center. Ratings increased with nurses' knowledge of patients and for older
      patients.

PMID- 16816606
TI  - Nursing home staff's perceived ability to influence quality of life.
AB  - Nurses, certified nursing assistants, activity personnel, social workers, and
      physicians in 5 cities rated their ability to affect each of 17 quality of life
      (QoL) items for 2 hypothetical cases. Those closest to the residents feel the
      most empowered to make a difference. Overall, certified nursing assistants were
      consistently the most optimistic about their ability to influence QoL.
      Perceptions of ability to influence QoL were correlated with attitudes about
      nursing homes. These perceptions may be helpful in retaining such staff.

PMID- 16816607
TI  - Reliability testing of the National Database of Nursing Quality Indicators
      pressure ulcer indicator.
AB  - A criterion-referenced Web-based test was designed and administered to 256
      individuals at 48 randomly sampled National Database of Nursing Quality
      Indicators (NDNQI) member hospitals to determine the reliability of the NDNQI
      pressure ulcer indicator. Overall kappa values for pressure ulcer identification,
      staging, and sourcing indicate moderate to near perfect reliability. Findings
      suggest that nurses can accurately differentiate pressure ulcers from other
      ulcerous wounds in Web-based photographs, reliably stage pressure ulcers, and
      reliably identify community versus nosocomial pressure ulcers.

PMID- 16816608
TI  - Impact of a nurse short message service intervention for patients with diabetes.
AB  - The purpose of this study was to investigate the effect of a nurse short message
      service by cellular phone and the Internet on glycosylated hemoglobin (HbA1c)
      levels and adherence to diabetes control recommendations. The patients with
      diabetes were asked to input their blood glucose levels every day by cellular
      phone or the Internet. Optimal recommendations were sent weekly to each patient
      by short message service. After 12 weeks, the patients had a mean decrease of
      1.1% in HbA1c level and an increase in diabetic medication taking, 30 minutes of
      physical exercise, and foot care adherence.

PMID- 16816609
TI  - Decreasing urinary tract infections through staff development, outcomes, and
      nursing process.
AB  - For patients with indwelling catheters, even with current standards of care and
      evidence-based practice, urinary tract infections continue to be a problem. Data
      were gathered on urinary catheter usage in a large, rural acute care hospital,
      and outcomes profiles were developed (including mortality, morbidity, length of
      stay, and costs). An innovative poster and video approach focusing on
      alternatives to urinary catheterization, early discontinuance of catheters, and
      proper insertion and care techniques were used to educate nursing staff and
      improve outcomes.

PMID- 16816610
TI  - Gender differences for Rapid After Bypass Back Into Telemetry tract following
      cardiac surgery.
AB  - The Rapid After Bypass Back Into Telemetry program is based on a simple clinical
      algorithm to predict same-day transfer of patients to the cardiac telemetry unit
      following cardiac surgery. This program proved to be an excellent predictor for
      decreased postoperative complications, shorter intensive care unit and hospital
      stay, and lower costs. We believe that any candidate for cardiac surgery should
      be screened for eligibility to participate in the program with special focus on
      female patients to further improve their outcomes.

PMID- 16816624
TI  - Managing pruritus.

PMID- 16816625
TI  - Oxygen delivery device can also deliver infections.

PMID- 16816626
TI  - Building on Mexican-American cultural values.

PMID- 16816627
TI  - Playing your part in a clinical trial.

PMID- 16816628
TI  - ACTH stimulation: Testing the adrenals.

PMID- 16816629
TI  - Intravenous fluids: the whys and wherefores.

PMID- 16816638
TI  - Myths and facts... About breast cancer in men.

PMID- 16816639
TI  - Caring for your patient's suprapubic catheter.

PMID- 16816648
TI  - Managing systolic heart failure.

PMID- 16816650
TI  - So you've been named in a lawsuit?: What happens next?

PMID- 16816651
TI  - Patient education series. Protecting yourself against medical errors.

PMID- 16816652
TI  - Which analgesic is right for my patient?

PMID- 16816657
TI  - First aid for bee, wasp, & hornet stings: learn how to protect the victim-and
      yourself-from the potentially dangerous effects of their venom.

PMID- 16816658
TI  - Here's HELP to prevent delirium in the hospital.

PMID- 16816660
TI  - Pertussis.

PMID- 16816661
TI  - Does reduction mammaplasty improve lung function test in women with macromastia?
      Results of a randomized controlled trial.
AB  - BACKGROUND: To determine the effects of reduction mammaplasty on lung function in
      women with mammary hypertrophy (macromastia), a prospective, randomized,
      controlled trial was conducted at the Academic Surgery and Plastic Surgery Units,
      Castle Hill Hospital, Cottingham, United Kingdom. METHODS: Seventy-three women
      who were referred for consideration of bilateral breast reduction surgery were
      randomized into either an early intervention group (surgery within 6 weeks) or a
      control group (surgery 6 months after recruitment). Each group had two sets of
      lung function tests: the intervention group had one before and one 3 months after
      surgery and the control arm had one test initially and a second test 4 months
      after randomization and before surgery. The main outcome measure was the lung
      function test. RESULTS: Sixty-five patients completed the study. The mean age was
      39 years (SD, 12 years); both groups were equally matched for age, smoking
      status, social class, and educational status. By independent t test, there was no
      significant difference in lung function in the two groups. Subgroup analysis of
      the intervention group demonstrated a positive correlation between specimen
      weight and forced expiratory volume/vital capacity, forced expiratory
      volume/forced vital capacity, peak expiratory flow rate, and forced vital
      capacity. A paired sample t test revealed a significant improvement in the
      percentage of forced vital capacity performed/forced vital capacity predicted.
      CONCLUSION: The improvement in pulmonary function following reduction mammaplasty
      correlates with specimen weight resected.

PMID- 16816662
TI  - Mandible augmentation for osseointegrated implants using tissue engineering
      strategies.

PMID- 16816663
TI  - Free flaps harvested from paralytic lower extremities in patients with late polio
      sequel.

PMID- 16816665
TI  - Use of regenerative human acellular tissue (AlloDerm) to reconstruct the
      abdominal wall following pedicle TRAM flap breast reconstruction surgery.
AB  - BACKGROUND: Harvest of transverse rectus abdominis musculocutaneous (TRAM) flaps
      for breast reconstruction leaves a variable defect in the anterior rectus fascia.
      Inadequate closure of the defect could lead to the development of hernia or
      abdominal wall bulging. Various techniques have been developed to reduce the
      incidence of hernia and abdominal wall bulging. The authors describe a novel
      technique of using a regenerative human acellular matrix (AlloDerm) as a fascial
      substitute in closing the defect. METHODS: Fifty-four consecutive patients who
      opted for pedicle TRAM flap procedures for breast reconstruction postmastectomy
      were scheduled for donor-site repair with the use of AlloDerm. AlloDerm was
      placed interpositionally as an inlay graft to mimic the anterior rectus fascia.
      RESULTS: Hernia or infection did not develop in any of the patients. There was a
      greater incidence of seroma and bulging among the first 18 patients, with eight
      seromas (44.4 percent) and six bulges (33.3 percent). When the technique was
      ameliorated in the next 36 patients, there was a reduction in the incidence of
      seromas (16.7 percent, p = 0.03) and bulges (16.7 percent, p = 0.17). Of the
      three patients who experienced wound dehiscence, partial AlloDerm exposure
      occurred in two, but was resolved without further consequences. Biopsy specimens
      of AlloDerm, obtained 12 and 14 months after TRAM donor-site repair, showed full
      tissue integration. The cell density, vasculature, and collagen orientation in
      the biopsies were consistent with abdominal fascia tissue. CONCLUSION: Based on
      these results, the authors recommend the use of AlloDerm as an alternative option
      for abdominal fascia closure after TRAM flap harvest for breast reconstruction.

PMID- 16816667
TI  - Intracranial extension of a zygoma fracture: benefits of selective repair.

PMID- 16816668
TI  - Frequently used grafts in rhinoplasty: nomenclature and analysis.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Accurately name the most frequently used grafts in primary and secondary
      rhinoplasty. 2. Describe the precise anatomical position of each graft. 3.
      Discuss the clinical indications of each graft. SUMMARY: In this article, the
      authors present the grafting techniques most commonly used to sculpt the nasal
      framework in primary and secondary rhinoplasty. The grafts are described in terms
      of their nomenclature, anatomical location, and clinical indications, presenting
      a simple and easy-to-reference guide for both beginners and expert surgeons.

PMID- 16816669
TI  - Breast reconstruction in older women: should age be an exclusion criterion?
AB  - BACKGROUND: At present, breast reconstruction is undertaken by fewer than 10
      percent of breast cancer patients undergoing mastectomy. Even though the benefits
      are numerous, this finding is even more notable among older women. Traditionally,
      women older than the age of 60 have been offered implant reconstruction or no
      reconstruction at all in hopes of minimizing potential morbidity. This practice
      may be due to a number of factors including a lack of patient education and
      information, as well as physician/surgeon bias regarding the safety or relevance
      of breast reconstruction in older women. METHODS: The authors undertook a
      retrospective study in which they surveyed 75 women (age range, 60 to 77 years)
      from two surgeons' practices who underwent various forms of breast reconstruction
      over the past 8 years. Type of reconstruction, recovery time, and complication
      rate were correlated with patient satisfaction, general health, and quality of
      life. RESULTS: An 81 percent response rate was obtained, yielding an average age
      of 66.6 years over a 3.8-year period. The overall rate of complications requiring
      operative intervention was 20.5 percent. When asked whether age should be a
      determining factor for breast reconstruction, more than 90 percent felt that it
      should not be. Only 16.1 percent of patients who had a delayed reconstruction
      stated that the option of breast reconstruction was presented to them at the time
      of their diagnosis, although 100 percent felt that it should have been. A
      significantly poorer physical health score was found among patients who
      experienced a complication, and lower mental health scores correlated with women
      who were less satisfied with their outcome. CONCLUSIONS: The authors believe that
      all types of reconstruction should be an option for women older than 60 years of
      age and that age as an isolated factor should not deter physicians from offering
      these women the option of breast reconstruction.

PMID- 16816670
TI  - A novel reconstructive technique following central lumpectomy.

PMID- 16816671
TI  - Induction of heat shock proteins in a rat composite tissue allotransplantation
      model of acute rejection.
AB  - BACKGROUND: Clinical cases of composite tissue allotransplantation have been
      reported, but the exact mechanisms of allograft rejection remain unclear. The
      current study examined the possible involvement of heat shock proteins in major
      histocompatibility complex-compatible minor-mismatch composite tissue
      allotransplantation rejection. METHODS: Allotransplantation (Fisher 344 to Lewis)
      and isotransplantation (Lewis to Lewis) of rat lower extremities were performed.
      Temporal profiles of 70-kDa and 60-kDa heat shock proteins (heat shock protein 70
      and heat shock protein 60) were conducted by quantitative Western blot analysis
      and immunohistochemistry. Analyses were performed immediately after reperfusion
      (day 0) and on postoperative days 1, 3, 7, and 12 (n = 5 for quantitative Western
      blot analysis and n = 5 for immunohistochemistry). RESULTS: The expression levels
      of the inducible forms of heat shock protein 70 and heat shock protein 60 were
      uniformly and significantly augmented until postoperative day 7 in the
      allografts, compared with the isografts (p < 0.001 for each protein).
      Immunoreactivities to heat shock protein 70 and heat shock protein 60 in
      keratinocytes, hair follicular cells, and endothelial cells of the subdermal
      vascular plexus were enhanced in the allografts early on postoperative day 1.
      Positive staining of hair follicles extended to deeper parts of the hair
      follicles and hair bulbs in the allografts on postoperative day 3. Although
      dendritic cells were positive for both heat shock protein 70 and heat shock
      protein 60, infiltrating lymphocytes were positive only for heat shock protein
      60. CONCLUSIONS: These results suggest the possible involvement of heat shock
      proteins in the process of major histocompatibility complex-compatible minor
      mismatch composite tissue allotransplantation rejection. Thus, modulation of the
      function of heat shock proteins might be an important therapeutic option for
      improving the outcome of minor-mismatch allografts.

PMID- 16816672
TI  - Tissue engineering cartilage with aged articular chondrocytes in vivo.
AB  - BACKGROUND: Tissue engineering has the potential to repair cartilage structures
      in middle-aged and elderly patients using their own "aged" cartilage tissue as a
      source of reparative chondrocytes. However, most studies on tissue-engineered
      cartilage have used chondrocytes from postfetal or very young donors. The authors
      hypothesized that articular chondrocytes isolated from old animals could produce
      neocartilage in vivo as well as articular chondrocytes from young donors.
      METHODS: Articular chondrocytes from 8-year-old sheep (old donors) and 3- to 6
      month-old sheep (young donors) were isolated. Cells were mixed in fibrin gel
      polymer at 40 x 10 cells/ml until polymerization. Cell-polymer constructs were
      implanted into the subcutaneous tissue of nude mice and harvested at 7 and 12
      weeks. RESULTS: Samples and native articular cartilage controls were examined
      histologically and assessed biochemically for total DNA, glycosaminoglycan, and
      hydroxyproline content. Histological analysis showed that samples made with
      chondrocytes from old donors accumulated basophilic extracellular matrix and
      sulfated glycosaminoglycans around the cells in a manner similar to that seen in
      samples made with chondrocytes from young donors at 7 and 12 weeks. Biochemical
      analysis revealed that DNA, glycosaminoglycan, and hydroxyproline content
      increased in chondrocytes from old donors over time in a pattern similar to that
      seen with chondrocytes from young donors. CONCLUSIONS: This study demonstrates
      that chondrocytes from old donors can be rejuvenated and can produce neocartilage
      just as chondrocytes from young donors do when encapsulated in fibrin gel polymer
      in vivo. This study suggests that middle-aged and elderly patients could benefit
      from cartilage tissue-engineering repair using their own "aged" articular
      cartilage as a source of reparative chondrocytes.

PMID- 16816674
TI  - Biologic brachytherapy: ex vivo transduction of microvascular beds for efficient,
      targeted gene therapy.
AB  - BACKGROUND: Gene therapy for cancer holds enormous therapeutic promise, but its
      clinical application has been limited by the inability to achieve targeted, high
      level transgene expression with limited systemic toxicity. The authors have
      developed a novel method for delivering genes to microvascular free flaps
      (commonly used during reconstructive surgery) to avoid these problems. METHODS:
      During the finite period in which a free flap is separated from the host (ex
      vivo), it can be perfused with extremely high titers of genetic material through
      the afferent artery, resulting in efficient transduction of the tissue. Before
      reanastomosis, unincorporated genetic material is flushed from the flap,
      minimizing systemic toxicity. RESULTS: In a rodent model using an adenoviral
      vector containing the lacZ reporter gene, high regional expression of beta
      galactosidase was achieved in all the different cells in a microvascular free
      flap. Moreover, no beta-galactosidase staining was observed outside of the
      transduced flap, and viral sequence was undetectable by polymerase chain reaction
      analysis in other tissues. Further analysis confirmed that high-level transgene
      expression was precisely localized to the explanted tissue, with no collateral
      transduction. CONCLUSIONS: Targeting gene delivery with minimal systemic toxicity
      is essential for successful gene therapy. This form of "biological brachytherapy"
      provides a new opportunity to deliver targeted therapeutic transgenes to patients
      undergoing reconstructive surgery and allows microvascular free flaps to perform
      therapeutic and reconstructive functions.

PMID- 16816676
TI  - The effects of cavernous nerve grafting following surgically induced loss of
      erectile function in a large-animal model.
AB  - BACKGROUND: Prostate cancer is the second most common cause of cancer deaths in
      men in the United States. Many patients experience partial or complete loss of
      erectile function following prostatectomy. The cavernous nerves can be
      reconstructed intraoperatively using sural nerve grafts in an attempt to restore
      erectile function. METHODS: In this study, multiple anatomical dissections and
      neurologic assessments were used to define the position and histologic parameters
      of the cavernous nerve in a canine model. The subsequent experimental design
      included three groups of adult mongrel dogs followed for an 8-month period. Group
      1, the control group, underwent bilateral nerve ablation to substantiate
      surgically induced loss of erectile function. Group 2, the "sham" group,
      underwent exploration only. Group 3 underwent bilateral cavernous nerve ablation
      with bilateral sural nerve graft reconstruction. Erectile function was evaluated
      with indirect electrical nerve and manual penile stimulation preoperatively and
      1, 2, 4, 6, and 8 months postoperatively. Direct nerve stimulation and histologic
      analysis was preformed at the first operation and at the time the animals were
      euthanized at 8 months. RESULTS: Bilateral cavernous nerve ablation resulted in a
      significant loss of erectile function for 8 months postoperatively in the control
      animals. The sham animals demonstrated preservation of erectile function
      immediately following exploration. The animals in the grafted group demonstrated
      a significant return of erectile function by 4 months compared with preoperative
      measurements and by 2 months compared with control animals. CONCLUSIONS: This
      study establishes the first large-animal model for surgically induced loss of
      erectile function with successful cavernous nerve graft reconstruction, and it
      provides the unique opportunity to explore the effects of changes to this model
      in the future.

PMID- 16816677
TI  - The fetal cleft palate: IV. Midfacial growth and bony palatal development
      following in utero and neonatal repair of the congenital caprine model.
AB  - BACKGROUND: Midfacial hypoplasia and growth disturbances following cleft palate
      repair are well-known consequences of the maxillary scarring inherent with each
      repair technique. The present study investigated the influence of in utero
      palatoplasty, and cleft repair in 6-week-old goats, on midfacial growth and bony
      palatal development in the authors' congenital caprine cleft palate model in an
      effort to identify an inherent component of facial growth impairment associated
      with the cleft anomaly. METHODS: At 85 days' gestation, eight clefted fetuses
      underwent in utero cleft palate repair using a modified von Langenbeck technique;
      eight fetuses remained as unrepaired controls. At 6 weeks of age, eight goats
      underwent cleft palate repair using the same technique. All goats were euthanized
      at 6 months of age; dry skull measurements and cephalometric analyses were
      performed. RESULTS: Fetal Repairs: Both repaired and unrepaired clefted goats
      demonstrated significant evidence of maxillary hypoplasia compared with unclefted
      controls. Repaired goats showed a decrease of 15.7 percent in maxillary length,
      and unrepaired clefted goats showed a decrease of 18.0 percent in maxillary
      length, compared with unclefted controls. There was no significant difference in
      maxillary growth between the repaired and unrepaired clefted groups. Bony cleft
      width was reduced by 48 percent anteriorly and 60 percent posteriorly. Thirty
      seven percent of repaired congenital clefts demonstrated partial bony fusion
      involving 10 to 70 percent of the palatal length. This was accompanied by an 8.8
      percent decrease in maxillary width at the level of the third molar crown
      compared with unclefted controls and an 18.3 percent decrease in maxillary width
      compared with unrepaired clefted goats. Unrepaired clefted goats demonstrated
      neither a decrease in maxillary width nor any narrowing or fusion of the bony
      cleft. Newborn Repairs: Significant midfacial growth impairment was seen in
      animals that underwent cleft palate repair at 6 weeks of age compared with those
      repaired in utero and with unclefted controls. Repaired clefted goats
      demonstrated a significant decrease in maxillary length by 29.5 percent compared
      with unclefted controls and 16.4 percent compared with the group repaired in
      utero. Repaired goats also demonstrated a significant decrease in maxillary width
      in the transverse dimension at the level of the third molar. A decrease in
      maxillary width of 25.3 percent was seen compared with the unclefted controls and
      18.1 percent compared with the fetal repairs. Bony cleft width was reduced by 32
      percent anteriorly and 27 percent posteriorly following repair at 6 weeks of age.
      Although all goats demonstrated narrowing following repair, partial bony palatal
      fusion was not seen in this group. CONCLUSIONS: In utero cleft palate repair does
      not contribute to impairment of midfacial growth. The authors attribute this
      finding to the scarless nature of mucoperiosteal healing in the privileged fetal
      environment. However, the cleft palate anomaly does have an inherent component of
      facial dysmorphology that is evidenced as maxillary hypoplasia or retrusion in
      unrepaired clefted animals. Cleft repair in the newborn period, or thereafter,
      results in midfacial growth impairment in a manner similar to that seen
      clinically. The authors attribute this finding to the scarring that routinely
      accompanies conventional palatoplasty. The combination of the growth impairment
      inherent in the cleft anomaly and that attributable to postnatal repair scarring
      yields the midfacial retrusion commonly associated with cleft palate.

PMID- 16816678
TI  - Clinical and anatomical study of superficial cervical artery flaps: retrospective
      study of reconstructions with 41 flaps and the feasibility of harvesting them as
      perforator flaps.
AB  - BACKGROUND: The superficial cervical artery musculocutaneous flap was first
      reported by Nakajima and Fujino in 1984; the present authors developed it for use
      as a skin flap in 1990, and in 1993, they succeeded in harvesting it as a free
      flap. Since 1986, they have harvested 41 superficial cervical artery flaps of
      various types from 32 patients to reconstruct head and neck scar contractures and
      intractable ulcers. METHODS: In a retrospective clinical study, the authors
      classified these 41 flaps into three types according to their pedicles:
      musculocutaneous pedicled flaps (n = 5); muscle pedicled flaps (n = 14), and
      vascular pedicled flaps (n = 22). In an anatomical study, they harvested 10 flaps
      from five preserved cadavers and took microangiograms of the trapezius muscle and
      dorsal skin to identify the distribution of the superficial cervical artery.
      RESULTS: Thirty-six flaps survived completely, and both the aesthetic and
      functional results were good. Among the other five flaps, partial necrosis was
      observed in four and complete necrosis was seen in one. Among the 36 surviving
      flaps, 23 were more than 30 cm long. CONCLUSIONS: The authors fully confirmed
      from their clinical and anatomical studies that the superficial cervical artery
      flap is useful for reconstruction of the head and neck regions. In each flap, the
      superficial cervical artery was found to be a "transverse cervical perforator" or
      "trapezius perforator" and was large enough to be used as a vascular pedicled
      flap, suggesting that it can be elevated as a "perforator flap."

PMID- 16816679
TI  - Release and free flap reconstruction for trismus that develops after previous
      intraoral reconstruction.
AB  - BACKGROUND: Oral cancer patients receive wide excision of oral structures and
      reconstruction of the intraoral defects with skin grafts and/or local, regional,
      or free flaps. Trismus is a common postoperative sequela, even without
      postoperative radiotherapy. Trismus decreases patients' quality of life and can
      have detrimental effects on their oral hygiene and nutritional status. METHODS:
      Between May of 1999 and June of 2003, 11 patients were operated on for release of
      trismus and reconstruction after previous intraoral reconstructions. The patients
      had been reconstructed with skin grafts (n = 4), radial forearm flaps (n = 3),
      anterolateral thigh flaps (n = 1), artificial dermis (n = 1), radial forearm
      flaps with skin grafts (n = 1), and pedicled pectoralis major flaps with skin
      grafts (n = 1). Eight patients had received postoperative radiotherapy. The
      patients presented with a mean interincisal distance of 3.1 mm (range, 0 to 10
      mm). RESULTS: After trismus release, the intraoral soft-tissue defects were
      reconstructed with one or two free flaps (six anterolateral thigh flaps, nine
      forearm flaps, and one fibula osteoseptocutaneous flap). Fifteen of the 16 flaps
      were successful, with one flap failure. Average interincisal distance was 33.4 mm
      immediately after the release (range, 27 to 35 mm) and 18.9 mm (range, 5 to 30
      mm) at a mean follow-up time of 22.7 months (16.1 mm in the radiated group and
      26.3 mm in the nonradiated group). The mean amount of improvement was 15.8 mm.
      CONCLUSION: The use of free flaps to reconstruct the defects created after
      trismus release in patients with previous intraoral reconstruction is a viable
      option that yields reasonable, long-lasting improvements in mouth opening,
      intraoral hygiene, and quality of life.

PMID- 16816680
TI  - Monitoring buried free flaps: limitations of the implantable Doppler and use of
      color duplex sonography as a confirmatory test.
AB  - BACKGROUND: Postoperative monitoring of free flaps is important to minimize the
      risk of flap failure, but monitoring buried free flaps is difficult because the
      standard methods of clinical examination and surface Doppler monitoring are not
      possible. Buried free flaps are often monitored using an implantable 20-MHz
      ultrasonic Doppler probe. METHODS: The authors conducted a retrospective clinical
      study of buried free flaps to assess the reliability of the implantable Doppler
      probe in postoperative monitoring of free flaps. RESULTS: During the 38-month
      study period, 956 free flap operations were performed at the authors'
      institution. Twenty (2.1 percent) of these cases involved completely buried free
      flaps in which an implantable Doppler probe was used for flap monitoring.
      Implantable Doppler probe monitoring had a 100 percent sensitivity rate in
      detecting loss of flap perfusion, making it a good screening test for free flap
      viability. However, it suffered from a high false-positive rate of 88 percent,
      which resulted in a high proportion of subsequent negative surgical explorations.
      In one case, color duplex sonography, a rapid and noninvasive test, revealed that
      the loss of signal from the implantable Doppler probe was a false-positive
      result. CONCLUSIONS: The implantable Doppler probe is a sensitive method for
      postoperative monitoring of free flaps but is prone to false-positive signals.
      The use of color duplex sonography to confirm implantable Doppler probe findings
      may avert unnecessary surgical exploration, thereby improving postoperative
      monitoring of free flaps.

PMID- 16816682
TI  - Prediction of morbidity and mortality on admission to a burn unit.
AB  - BACKGROUND: Improvements in burn care during the last two decades call for new
      prediction models of morbidity and mortality. The aim of the study was to
      identify parameters that are predictive of major morbidity factors and risk of
      mortality in patients with burn injury. METHODS: The charts of 249 patients (236
      survivors) aged 1 to 94 years who were treated for second- and third-degree burns
      from 1995 to 2002 were reviewed. A multivariate linear stepwise regression model
      was fitted to the data to predict length of hospitalization, length of
      operations, and mortality rate. RESULTS: Survivors' mean burn size was 14 +/- 15
      percent of the total body surface area (range, 5 to 90 percent), with a mean
      hospitalization time of 22.9 +/- 17.1 days and a mean operative time of 127.5 +/-
      166.8 minutes. The prognostic factors in each of the regression models predicted
      40 percent and 55 percent of the variance in length of hospital stay and
      operative time, respectively. Total body surface area alone explained most of the
      variance (29 percent and 44 percent, respectively). As a result, the authors
      created shorter formulas: Length of hospitalization (days) = 18 + [total body
      surface area]/3; Operative time (minutes) = 55 + 4[total body surface area].
      Total body surface area and smoke inhalation were the only statistically
      significant predictors of death. Every 1 percent increase in total body surface
      area was associated with a 6 percent increase in mortality risk. The presence of
      smoke inhalation increased mortality risk by nine-fold. CONCLUSIONS: Using
      objective measurements in burn treatment is of great importance. The formulas
      presented by the authors explain a considerable percentage of the probability of
      morbidity in burn victims. The authors suggest that other burn units develop
      their own statistically supported prediction models.

PMID- 16816683
TI  - Why not indirect nonmuscle perforator flaps?

PMID- 16816684
TI  - Expanding the scope of the turnover flap.
AB  - BACKGROUND: Turnover flaps are often utilized as alternatives to more traditional
      flaps, especially in situations where traditional flap viability is limited. Most
      turnover flaps are currently used in the lower extremities. METHODS: This study
      examined the senior author's use of the turnover flap in 103 cases between 1987
      and 2004. Postoperative follow-up ranged from 3 months to 10 years, with an
      average follow-up of 9 months. RESULTS: The majority (n = 90) of the cases
      involved the lower extremities and carried high success rates; there were 72
      successful operations (complete graft take), 10 partial flap losses (partial
      graft take that could be treated postoperatively without surgery), and eight
      complete flap losses (no graft take and the necessity of additional surgery).
      Three of the partial flap losses and two of the complete flap losses involved
      patients with end-stage vascular disease. End-stage vascular disease cases
      represented 20.0 percent of the lower extremity cases and carried a significantly
      higher percentage of partial or complete flap loss (27.8 percent). These
      circumstances were examined in detail; the authors found that the turnover flap
      provided improved outcome to such end-stage patients who otherwise would have
      undergone amputation. In 13 cases, turnover flaps were utilized in nontraditional
      regions, such as the chest wall, abdominal wall, head and neck region, and upper
      extremities, with a high degree of success (zero partial or complete flap
      losses). These approaches are discussed in detail. The surgical approach is
      examined with recommendations regarding preferred wound size and type and overall
      flap design. CONCLUSIONS: This study indicates that turnover flaps are effective
      and useful as an alternative and, in some cases, primary procedure. In addition,
      the results serve to expand the present scope of the turnover flap by examining
      nontraditional regions in which the flap was highly successful. The authors
      believe the turnover flap should be given higher priority as a reconstructive
      option, but more research is needed to explain the sources of blood supply in
      these flaps.

PMID- 16816685
TI  - A technique for localizing and removing a radio-opaque foreign body.

PMID- 16816686
TI  - Staged versus simultaneous bilateral endoscopic carpal tunnel release: an outcome
      study.
AB  - BACKGROUND: This study compared outcomes of bilateral simultaneous endoscopic
      carpal tunnel release to staged release using the Levine-Katz outcome instrument
      and physical measurements. METHODS: Seventy-one patients were evaluated
      preoperatively and at 6 months postoperatively. One group underwent simultaneous
      releases, a second group underwent staged releases 1 to 3 weeks apart, and a
      third underwent staged releases more than 3 weeks apart. Preoperative data
      included age, gender, race, medical history, initial symptom severity score, and
      body mass index. Preoperative and postoperative data included Semmes-Weinstein
      testing, grip and pinch strength, Tinel's sign, Phalen's test, Levine-Katz
      questionnaire, occupational history, postoperative complications, and patient
      satisfaction. RESULTS: Groups were similar demographically except that the
      simultaneous group had more men and patients were younger. Level of preoperative
      symptom severity was similar in all groups. Physical measurements were similar
      for all groups preoperatively and improved similarly at follow-up. All groups
      improved Levine-Katz mean symptom severity score and functional status score at
      follow-up. The groups had no significant difference in number of complications,
      and patient satisfaction was similar. CONCLUSIONS: In selected patients,
      bilateral simultaneous endoscopic carpal tunnel release has an outcome similar to
      that for surgery staged weeks apart. However, patients who choose simultaneous
      surgery may benefit from a shorter postoperative disability period and earlier
      return to work.

PMID- 16816688
TI  - Angiosome territories of the nerves of the upper limbs.
AB  - BACKGROUND: The use of free vascularized nerve grafts requires intimate knowledge
      of the blood supply of peripheral nerves. The authors aimed to demonstrate
      radiographically the topography of the upper limb nerves with their blood supply,
      and to examine them as an application of the angiosome concept. An angiosome is a
      three-dimensional block of composite tissue supplied by a single source artery.
      METHODS: This anatomical study involved the meticulous dissection of four fresh
      upper limb specimens injected intraarterially with a gelatin-lead oxide mixture.
      The nerves were tagged circumferentially with copper wire and radiographs were
      taken of the nerves with their arterial blood supply. The median, ulnar, radial,
      musculocutaneous, and axillary nerves were examined. RESULTS: The authors showed
      that the nerves of the upper limb were supplied segmentally by source vessels,
      which reinforced the angiosome concept. The suitability of each nerve for harvest
      in free vascularized nerve transfer was assessed according to its pattern of
      blood supply. CONCLUSIONS: The authors' work has a wide range of clinical
      applications and provides an anatomical basis for neurovascular and
      neurocutaneous flaps and free vascularized nerve grafting.

PMID- 16816689
TI  - Increased prevalence of community-acquired methicillin-resistant Staphylococcus
      aureus in hand infections at an urban medical center.
AB  - BACKGROUND: The purpose of this article is to report the increased incidence of
      community-acquired methicillin-resistant S. aureus in hand infections at an urban
      medical center. METHODS: The authors performed a retrospective review of all
      patients with hand infections over a 21-month period, and all patients with
      culture-positive methicillin-resistant S. aureus were identified. Cases
      determined to be nosocomial were excluded. The study period was divided into
      three 7-month periods. RESULTS: A total of 343 hand infections were treated over
      a 21-month period. Eighty-nine patients (26 percent) with culture positive
      methicillin-resistant S. aureus were identified; of these, 75 were determined to
      be community-acquired methicillin-resistant S. aureus patients. Statistical
      analysis was performed using the Fisher's exact test (p < 0.0001), the chi-square
      test for equal proportions, the Cochran-Armitage trend test, and two-way analysis
      of variance. The demographics of the patients were compared using two-way
      analysis of variance, and patients were found to be similar in all three time
      periods with respect to mean age and sex. The incidence of community-acquired
      methicillin-resistant S. aureus increased to 40 percent during the last 7-month
      period compared with 14 percent during the first two periods. Overall, the
      incidence of methicillin-resistant S. aureus increased to 47 percent during the
      last 7 months compared with 16 percent and 17 percent in the first two 7-month
      periods, respectively. Based on their treatment approach and literature review,
      the authors have developed an algorithm to treat community-acquired methicillin
      resistant S. aureus hand infections. CONCLUSIONS: The authors' findings at Temple
      University Hospital may help to alert health care providers to take necessary
      steps to control the spread of methicillin-resistant S. aureus in the community
      and in the inpatient setting. Cultures should be carefully followed and
      infections should be treated with appropriate antibiotics.

PMID- 16816691
TI  - Subcutaneous laser treatment of axillary osmidrosis: a new technique.

PMID- 16816692
TI  - Intellectual outcomes in children and adolescents with syndromic and nonsyndromic
      craniosynostosis.
AB  - BACKGROUND: Craniosynostosis, the premature fusion of the skull bones, is a
      congenital deformity that has functional and morphologic implications. Cranial
      vault reconstructive surgery is required to improve skull shape and increase
      intracranial volume. Craniosynostosis disorders carry a risk of brain insult and
      associated neurologic and cognitive dysfunction. This study investigated the long
      term effects of craniosynostosis on intelligence in children and adolescents with
      syndromic and nonsyndromic disorders who had undergone cranial expansion surgery
      during infancy. METHODS: Global intellectual evaluations were obtained on 31
      children aged 7 to 16 years with mixed syndromic (n = 13) and nonsyndromic (n =
      18) craniosynostoses. Results of intellectual assessment were compared with norm
      referenced data. Age at surgery and gender comparisons were also made. RESULTS:
      Mean +/- SD general intelligence quotient of the total sample was within the
      average range (intelligence quotient, 95.6 +/- 21.2). Intellectual functioning
      was significantly lower in children with syndromic craniosynostosis (mean
      intelligence quotient, 83.1 +/- 21.9) than nonsyndromic craniosynostosis (mean
      intelligence quotient, 104.7 +/- 15.8). The majority of children with syndromic
      craniosynostosis (77 percent) were of normal intelligence. Children with
      nonsyndromic craniosynostosis did not display obvious evidence of intellectual
      dysfunction. There were no age or gender differences in intellectual outcomes in
      this sample. CONCLUSIONS: Findings are contrary to the historical impression that
      has regarded syndromic craniosynostosis as synonymous with intellectual
      disability. Children with nonsyndromic craniosynostosis are of normal
      intelligence during their school-age years.

PMID- 16816694
TI  - Prevalence of abnormal pattern reversal visual evoked potentials in
      craniosynostosis.
AB  - BACKGROUND: The purpose of this study was to examine the prevalence and type of
      changes observed in the pattern reversal visual evoked potentials recorded at the
      first assessment of children with craniosynostosis. METHODS: Visual evoked
      potentials were recorded from 114 patients with craniosynostosis. Eighty-one
      patients were syndromic and 33 were nonsyndromic. No patient had received any
      craniofacial surgical intervention. At the time of the test, 22 of 40 patients
      were aged 6 months and younger, and 18 patients were between 6 months and 1 year
      of age. Pattern reversal visual evoked potentials were recorded from a
      midoccipital electrode positioned 3 cm above the inion. The pattern reversal
      visual evoked potentials elicited to 50' checks with three reversals per second
      viewed with both eyes were analyzed for n80-p100 amplitude, p100 latency, and
      breadth of waveform. RESULTS: Sixty percent of patients had abnormal pattern
      reversal visual evoked potentials to 50' checks. This did not show a significant
      association with age, or classification of craniosynostosis. CONCLUSIONS: The
      high prevalence of abnormal pattern reversal visual evoked potentials to a robust
      stimulus suggests that visual pathway dysfunction, as measured
      electrophysiologically, can affect a majority of patients with craniosynostosis.
      This study indicates that a baseline evaluation of all children with
      craniosynostosis at their first presentation is essential if subsequent
      electrophysiologic visual pathway monitoring is to take place.

PMID- 16816695
TI  - Two-flap palatoplasty: 20-year experience and evolution of surgical technique.
AB  - BACKGROUND: The two-flap palatoplasty was described more than 30 years ago, but
      there are few reports of long-term results using this technique. There are also
      very few long-term series of a single method of palatoplasty from a single
      surgeon. METHODS: The authors reviewed the technique of the two-flap
      palatoplasty, with emphasis on the senior author's (K.E.S.) modifications. The
      authors also retrospectively reviewed 382 two-flap palatoplasties performed by
      the senior author in nonsyndromic patients over a 20-year period. The incidence
      of secondary velopharyngeal surgery was established. Detailed speech analysis was
      performed in a subset of 150 patients. RESULTS: The proportion of patients with
      velopharyngeal insufficiency over 20 years was 8.92 percent, falling from 10.95
      percent in the first decade to 6.43 percent in the second decade. There was no
      significant difference in velopharyngeal insufficiency between the cleft
      subtypes. Age at palatoplasty did not affect the development of velopharyngeal
      insufficiency, but it should be noted that most of the patients underwent palate
      repair before 12 months of age. Speech results were consistently good across the
      two decades. In the second decade, 91.14 percent had normal to mildly impaired
      resonance, 79.75 percent had no or inaudible nasal air emission, and 97.47
      percent demonstrated no compensatory articulation errors. CONCLUSIONS: The two
      flap palatoplasty is a reliable technique that has yielded excellent surgical and
      speech outcomes. Early and regular speech assessments and appropriate treatment
      when indicated are an integral part of the multidisciplinary approach to achieve
      good speech outcome.

PMID- 16816696
TI  - Is it safe to combine abdominoplasty with elective breast surgery? A review of
      151 consecutive cases.
AB  - BACKGROUND: This study was designed to evaluate and compare the complication
      rates of patients having abdominoplasty without breast surgery with the rates of
      those having abdominoplasty with various types of elective breast surgery,
      including breast augmentation, breast reduction, mastopexy, and mastopexy
      combined with simultaneous augmentation. METHODS: The data collected represent a
      retrospective chart review of consecutive abdominoplasty procedures performed at
      a single outpatient facility by the senior surgeon (W.G.S.) over a 15-year period
      (1989 to 2004). Two groups were compared: patients who underwent abdominoplasty
      without breast surgery and those who had abdominoplasty with breast surgery. The
      second group was subdivided by the various types of breast procedures noted
      above. The minor complications assessed included seromas, hematomas, infections,
      and small (<5 cm) wound breakdowns. Major complications evaluated included large
      (>5 cm) flap necrosis, need for blood transfusion, deep vein thrombosis,
      pulmonary embolus, myocardial infarction, and death. Additional data compiled
      included age, sex, tobacco use, body mass index, past medical history, American
      Society of Anesthesiologists physical status level, and operative times. RESULTS:
      Of the 415 abdominoplasty procedures, 264 (group 1) did not include simultaneous
      breast surgery. One hundred fifty-one procedures (group 2) involved simultaneous
      breast surgery, representing 36 percent of the total. Group 2 was further
      subdivided into those who had breast augmentation surgery (group 2A, n = 50),
      those who had breast reduction surgery (group 2B, n = 31), those who had
      mastopexy surgery (group 2C, n = 28), and those who had simultaneous mastopexy
      and breast augmentation surgery (group 2D, n = 42). Removal and replacement of
      implants and capsulectomy/capsulotomy procedures were included in the
      augmentation group (group 2A). There were no major complications, including flap
      necrosis (open wound >5 cm), blood transfusions, deep vein thrombosis, pulmonary
      embolus, myocardial infarction, or death. No patients required hospitalization.
      No statistically significant associations with complications were noted between
      groups 1 and 2 (chi-square, 0.0045; p > 0.95, not significant). Furthermore, when
      subdivided by type of breast surgery, no statistically significant associations
      were noted among subgroups: group 1 versus 2A (chi-square, 0.96; p > 0.05, not
      significant), group 1 versus 2B (chi-square, 0.032; p > 0.9, not significant),
      group 1 versus 2C (chi-square, 0.003; p > 0.975, not significant), and group 1
      versus 2D (chi-square, 0.83; p > 0.5, not significant). CONCLUSION: The results
      of this retrospective review indicate that combining elective breast surgery with
      abdominoplasty does not appear to significantly increase the number of major or
      minor complications.

PMID- 16816698
TI  - Textured saline-filled breast implants for augmentation mammaplasty: does
      overfilling prevent deflation? A long-term follow-up.
AB  - BACKGROUND: Augmentation mammaplasty is the second most commonly performed
      aesthetic operation. Since the moratorium on gel-filled devices in 1992, saline
      filled devices have become the prosthesis of choice in the United States.
      Although inflatable breast implants have been available since 1965, high rates of
      complete implant deflation have been reported. In this retrospective study, the
      authors highlight the effect of filling volume on the incidence of implant
      deflation, other implant-related trade-offs, and implant survival. METHODS: Forty
      nine women who had undergone aesthetic augmentation mammaplasty were followed up
      for up to 139 months. Twelve implants were underfilled (group 1), 47 devices were
      filled within the recommended volume (group 2), and 37 implants were overfilled
      beyond the manufacturer's maximum recommended volume (group 3). All the implants
      used were of the same type and from the same manufacturer (Siltex by Mentor,
      2600). Through an inframammary approach, subpectoral placement of the device was
      used exclusively. RESULTS: Nineteen women experienced complete deflation of their
      implants, with an overall implant complete deflation rate of 19.79 percent. This
      complication occurred in 16.6 percent of group 1 patients, 21.2 percent of group
      2, and 18.9 percent of group 3. Skin wrinkling and rippling were encountered in
      50 percent of group 1, 29.78 percent of group 2, and 43.2 percent of group 3,
      with an overall incidence of 37.5 percent. In this series, the authors could not
      find a protective effect of overfilling on complete deflation (p = 0.925) nor on
      the avoidance of rippling and wrinkling (p = 0.285). Moreover, overfilling by
      more than 25 ml beyond the maximum recommended dose showed no statistical
      significance for the frequency of complete deflation (p = 0.982) or for the
      incidence of wrinkling and rippling (p = 0.828). However, Kaplan-Meier survival
      analysis revealed that overfilling the implants prolonged their longevity and had
      a statistically significant effect on the implants' 10-year survival rate. Of the
      49 women, 34 (69.3 percent) needed a secondary surgical procedure, mainly for
      complete deflation (38.7 percent) and skin wrinkling/rippling (20.4 percent). At
      the end of the current study, eight of 49 women, representing 15 implants,
      retained their original implants for more than 120 months. CONCLUSIONS: Use of
      Mentor 2600 prostheses for aesthetic breast augmentation led to a very high
      incidence of complete deflation and skin wrinkling and a high reoperation rate.
      Filling the implants within the recommended range or overfilling them increased
      device longevity and had a statistically significant effect on the implants' 10
      year survival rate.

PMID- 16816700
TI  - Determination of serum fibrosis indexes in patients with capsular contracture
      after augmentation with smooth silicone gel implants.
AB  - BACKGROUND: Several studies have confirmed a correlation between the
      concentration of serum hyaluronan and progressive fibrotic disorders such as
      liver cirrhosis. The aim of this study was to explore the relationship between
      serum hyaluronan levels and capsular contracture after aesthetic breast
      augmentation. METHODS: The study included 25 female patients (average age, 40 +/-
      12 years) with capsular contracture after cosmetic breast augmentation with
      smooth silicone gel implants (Mentor, Santa Barbara, Calif.). The implants were
      placed in a submuscular position through an inframammary fold incision. The
      implant removals were prompted by development of capsular fibrosis (Baker grades
      I through IV). Samples of capsular tissue were obtained from all patients for
      standard histologic and immunohistochemical analysis. Blood samples were drawn
      from all patients immediately before operation. Sera from 20 healthy female
      patients (average age, 34 +/- 9 years) were used as control. RESULTS: : Capsular
      tissue revealed significantly higher thickness in patients with grade III/IV
      contracture than in women with grade II contracture, according to Baker's
      classification. There was a moderate (n = 15) or severe (n = 10) chronic
      inflammatory reaction in the capsules around the implants. Fibroblasts,
      fibroblast-like cells, and macrophages represented the major cell populations
      found within the fibrous capsules, along with scattered polymorphonuclear
      leukocytes, lymphocytes, plasma cells, and mast cells. In addition, activated
      CD4+ cells were detected. An inner layer with synovia-like metaplasia and
      multinucleated giant cells was found. There was a significantly higher level (p <
      0.05) of hyaluronan serum concentration in patients with capsular contracture (26
      +/- 14 microg/liter) compared with control subjects (12 +/- 6 microg/liter).
      There was a positive correlation between the grade of capsular contracture (Baker
      grades I through IV) and the hyaluronan serum concentration (Baker grade II, 15
      +/- 3 microg/liter; Baker grade III, 34 +/- 13 microg/liter; Baker grade IV, 42
      +/- 11 microg/liter) (r = 0.73; p < 0.05). CONCLUSIONS: Serum hyaluronan levels
      were significantly elevated in patients with capsular contracture after breast
      augmentation, and there was a positive correlation with stage of capsular
      contracture. Further study is necessary to determine whether hyaluronan might be
      useful as a predictor for the development and progress of capsular fibrosis.

PMID- 16816701
TI  - Histological analysis of human diced cartilage grafts.
AB  - BACKGROUND: Grafting the radix and dorsum of the nose has been controversial and
      the plastic surgery community has recently revisited diced cartilage grafts.
      Previous articles by the authors reported clinical failures of diced cartilage
      Surgicel-wrapped grafts and the successful implementation of diced cartilage
      fascia-wrapped grafts for rhinoplasty procedures. This article investigates four
      means of radix and dorsum augmentation, including banked and fresh septum.
      METHODS: Twenty-seven human specimens were taken from rhinoplasty patients: six
      failed diced cartilage-Surgicel-wrapped grafts, eight diced cartilage-fascia
      wrapped grafts, and 13 specimens of fresh cartilage or previously placed
      cartilage grafts. All were stained with hematoxylin and eosin, Masson's
      trichrome, safranin-O, glial fibrillary acidic protein, and Evans' van Gieson
      stains and analyzed for chondrocyte viability, matrix proteins, and regenerative
      potential of the cartilage. RESULTS: The diced cartilage-Surgicel-wrapped grafts
      showed disorganized fibrosis, loss of nuclei in chondrocyte lacunae, and negative
      glial fibrillary acidic protein staining. All specimens contained remnants of
      Surgicel and evidence of foreign body reaction. The diced cartilage-fascia
      wrapped grafts showed normal histologic characteristics, healthy cartilage pieces
      with viable chondrocytes in their lacunae, positive glial fibrillary acidic
      protein staining, and organized capsule of fibrosis surrounding the cartilage
      pieces. The fascia was viable and showed an organized architecture distinctly
      different from the disorganized scar tissue of the diced cartilage-Surgicel
      wrapped grafts. CONCLUSIONS: Given the histologic findings, diced cartilage
      Surgicel-wrapped grafts absorbed due to foreign body reaction. Diced cartilage
      fascia wrapped grafts survived and demonstrated normal cartilage viability.
      According to the clinical performance and analysis of these grafts, diced
      cartilage-fascia is the most reliable way to augment the nasal dorsum and radix
      with autologous diced cartilage.

PMID- 16816702
TI  - An algorithmic approach to upper arm contouring.
AB  - There has been a renewed interest in upper arm contouring given the recent
      advances and subsequent patient interest in weight loss. Patients undergoing
      bariatric surgery are often left with a significant amount of redundant skin and
      laxity of their upper extremity. Some patients within this group have excess fat
      in their upper arms with relatively good skin tone, while others have a paucity
      of excess fat with a significant amount of redundant skin. The optimal treatment
      for each patient can vary. A clinical algorithm is presented that is designed to
      select the best method for upper arm contouring based on the aesthetic analysis
      of the upper arm. Case examples are provided demonstrating results that were
      obtained by following this algorithm.

PMID- 16816703
TI  - Vitamin E: patterns of understanding, use, and prescription by health
      professionals and students at a university teaching hospital.
AB  - BACKGROUND: Vitamin E is a generic term used to describe the many derivatives of
      tocol and tocotrienol. It is the major lipid-soluble antioxidant in the skin and
      has been used as treatment for many skin conditions, including scarring. Studies
      have shown that vitamin E provides no benefit to the cosmetic outcome of scars.
      METHODS: The authors constructed and distributed a questionnaire among staff and
      students at their institution. Their aim was to determine patterns of use and
      prescription of vitamin E among staff and students and to determine the
      understanding of the properties and biological functions of vitamin E. RESULTS:
      Questionnaires were completed by 208 staff and students, including 110
      nonconsultant hospital doctors (52.89 percent), 61 nurses (29.33 percent), and 27
      medical students (12.98 percent). Nearly 68 percent thought that vitamin E could
      be of use in improving the cosmetic appearance of scars, while 25 percent
      actually recommended vitamin E to patients to improve the cosmetic outcome of
      scars. Just under 40 percent were aware of the biological function of vitamin E,
      while 16.35 percent thought vitamin E had absolutely no effect on scarring. Of
      respondents, 21.64 percent had used vitamin E for their own scars; 31.11 percent
      of these said it was suggested by a doctor, while 6.67 percent said a pharmacist
      suggested it. CONCLUSIONS: Without scientific basis, health professionals
      continue to recommend vitamin E for use on scars. Such recommendations should not
      be made in the absence of evidence-based medicine.

PMID- 16816704
TI  - Anti-aging medicine: part 3. Growth hormone replacement.

PMID- 16816705
TI  - "See one, do one, teach one": an old adage with a new twist.

PMID- 16816706
TI  - Ethics.

PMID- 16816709
TI  - Regarding the treatment of dynamic nasal tip ptosis with botulinum toxin A.

PMID- 16816710
TI  - The use of Adson-Brown forceps to score the cartilage in otoplasty.

PMID- 16816712
TI  - Response to "New-fill injections may induce late-onset foreign body granulomatous
      reaction".

PMID- 16816713
TI  - Use of axial pattern cervico-occipital flaps in restoration of beard defects.

PMID- 16816714
TI  - Revisiting the reconstructive ladder.

PMID- 16816716
TI  - Controversies following the report on transplantation of cephalocervical skin
      flap.

PMID- 16816717
TI  - The use of the pedicled supraclavicular flap in noma reconstructive surgery.

PMID- 16816718
TI  - "Keystone" approach for intracranial nasofrontal dermoid sinuses.

PMID- 16816719
TI  - Complications after Pi plate osteosynthesis.

PMID- 16816720
TI  - Involvement of the basilar coronal ring in unilateral coronal synostosis.

PMID- 16816721
TI  - Complication rates in inferior pedicle reduction mammaplasty.

PMID- 16816723
TI  - Deepithelialization of pedicle in breast reduction: the maze technique.

PMID- 16816724
TI  - Concern about "A prospective study of antibiotic efficacy in preventing infection
      in reduction mammaplasty".

PMID- 16816726
TI  - The ballooning maneuver in breast augmentation.

PMID- 16816727
TI  - "Flag" drain fixation: a secure method.

PMID- 16816728
TI  - The thoracoacromial vessels as recipient vessels in microsurgery and
      supermicrosurgery: an anatomical and sonographic study.

PMID- 16816729
TI  - Three-dimensional anatomical vascular distribution in the pectoralis major
      myocutaneous flap.

PMID- 16816730
TI  - Arterial supply to type II muscle after fasciocutaneous free flap transfer.

PMID- 16816732
TI  - Experiences in harvesting type II distally based anterolateral thigh flaps.

PMID- 16816734
TI  - Bone exposure in the leg: is a free muscle flap necessary?

PMID- 16816736
TI  - Defining vascular supply and territory of thinned perforator flaps: part I.
      Anterolateral thigh perforator flap.

PMID- 16816737
TI  - Nose elongation.

PMID- 16816738
TI  - Rhinoplasty and PubMed.

PMID- 16816739
TI  - Three-dimensional surgical videos: a new medium for supporting patient education
      before aesthetic surgery.

PMID- 16816740
TI  - Total nipple-areola complex necrosis in inferior pedicle breast reduction.

PMID- 16816741
TI  - Liposuction and pulmonary embolism: can we trust D-dimer values?

PMID- 16816742
TI  - Improving the cosmetic acceptability of punch biopsies: a simple method to reduce
      dog-ear formation.

PMID- 16816743
TI  - An efficient method to increase specificity of acoustic Doppler sonography for
      planning a perforator flap: perforator compression test.

PMID- 16816744
TI  - Improvement of the bipedicled fascial flap with a cutaneous V and Y island for
      coverage of the heel.

PMID- 16816745
TI  - Extramedullary multiple myeloma associated with amyloidomas of the lower limbs.

PMID- 16816746
TI  - Cutaneous island with V-Y closure over a gastrocnemius muscle flap.

PMID- 16816747
TI  - Exogenous cross-linking increases the stability of spinal motion segments.
AB  - STUDY DESIGN: The mechanical stability of cross-linked and control spinal motion
      segments was evaluated using neutral zone, range of motion (ROM), and instability
      score metrics. OBJECTIVE: To determine if exogenous cross-linking could increase
      the stability of spinal motion segments. SUMMARY OF BACKGROUND DATA: The
      microstructure of the anulus fibrosus extracellular matrix can affect the
      stability of the intervertebral joint. Parallel testing in our laboratory has
      shown that exogenous cross-linking can improve the fatigue resistance of anulus
      fibrosus. METHODS: There were 3 separate experimental protocols conducted. The
      first study used calf lumbar intervertebral joints randomly divided into a
      genipin cross-linked group and phosphate buffered saline-soaked controls. After 2
      days of soaking, flexion-extension ramp cycles were applied to the specimens. The
      second study repeated the test protocol using 22 moderately and severely
      degenerated human lumbar intervertebral joints. The third experiment compared the
      effect of cross-linking treatment on human discs with known degrees of
      preexisting mechanical instability. Each data set was used to assess joint
      instability by 3 calculations: ROM, neutral zone, and an instability score. Joint
      instability for each data set was evaluated using 3 calculations: ROM, neutral
      zone, and a novel instability score. RESULTS: These results show that cross-link
      augmentation can effectively reduce instability of intervertebral discs. The
      stabilizing effect was observed to be higher in the more mechanically unstable
      discs. However, cross-linking did not appear to affect the total range of
      sagittal motion. CONCLUSIONS: By reducing the neutral zone, exogenous cross
      linking may help combat the progression of instability in degenerative disc
      disease.

PMID- 16816748
TI  - Spatially varying material properties of the rat caudal intervertebral disc.
AB  - STUDY DESIGN: The use of a microscopy based material testing technique to assess
      the local material properties of rat caudal intervertebral discs under uniaxial
      compression. OBJECTIVES: To better understand the cell environment of rat caudal
      intervertebral discs during mechanical loading and elucidate better the role of
      the nucleus pulposus to the overall disc material properties. SUMMARY OF
      BACKGROUND DATA: Rat tail models of disc degeneration have been widely used for
      their similarity with the degeneration phenomena in human beings. Degenerative
      patterns in the disc are often inhomogeneous, however, only average material
      properties of rodent discs have been studied. Knowledge of the spatially varying
      properties within the disc is necessary to understand the disc cell milieu during
      tissue loading. METHODS: Rat caudal motion segments were tested intact,
      sectioned, and with alterations of nucleus pulposus using microscopy based
      techniques. Local displacements and strains were obtained using digital image
      correlation. Strains and load measurements were used to get the average apparent
      Young's modulus, peak stress, local Young's modulus, and local Poisson's ratio.
      RESULTS: There was no difference observed in the average apparent Young's modulus
      among experimental groups. Peak stresses decreased significantly when the nucleus
      pulposus was replaced with extremely fluid-like materials. The axial displacement
      field showed 3 distinct linear distributions in samples which were sectioned. The
      center region in all groups had significantly smaller axial strain and showed a
      higher local Young's modulus. CONCLUSIONS: The average equilibrium Young's
      modulus may be dependent on short-range ultrastructural organization. Spatially
      varying material properties within the intervertebral disc may be caused by
      orientation of fiber bundles in the different regions of the anulus fibrosus. The
      fiber bundles are better able to resist compressive loads when oriented parallel
      rather than perpendicular to the loading direction. At equilibrium, the anulus
      fibrosus also appears to have a shielding effect independent of the material
      filling up the nucleus pulposus space.

PMID- 16816749
TI  - Fatigue failure in shear loading of porcine lumbar spine segments.
AB  - STUDY DESIGN: An in vitro study on porcine spinal segments. OBJECTIVES: To
      determine the differences in mechanical behavior and fatigue strength in shear
      loading between intact spinal segments and segments without posterior elements,
      and between segments in neutral and flexed positions. SUMMARY OF BACKGROUND DATA:
      Limited data are available on shear strength of spinal segments. Literature
      suggests that shear loading can lead to failure of the posterior elements and
      failure of the disc, when the posterior elements cannot provide adequate
      protection. METHODS: In 2 experiments, 18 and 20 spines of pigs (80 kg) were
      used, respectively. Shear strength of the T13-L1 segment was tested, while loaded
      with 1600-N compression. L2-L3 and L4-L5 segments were loaded with a sinusoidal
      shear between 20% and 80% of the strength of the corresponding T13-L1 segment and
      1600-N compression. In experiment No. 1, the posterior elements were removed in
      half the segments. In experiment No. 2, half the segments were tested in the
      neutral position, and half were tested in 10 degrees flexion. RESULTS: The group
      without posterior elements had failure earlier than the intact group. In the
      group without posterior element, stiffness increased on failure; in the intact
      group, it decreased. In experiment No. 2, no differences between groups were
      found. CONCLUSIONS: Repetitive shear loading can induce failure of porcine spinal
      segments, likely caused by fracture of the posterior elements, and, although
      repetitive anterior shear forces can also induce disc damage, this appears not to
      occur in intact segments, not even when flexed close to maximal.

PMID- 16816750
TI  - Biomechanical comparison of augmentation techniques for insufficiency fractures.
AB  - STUDY DESIGN: Biomechanical laboratory research. OBJECTIVE: To compare 4
      techniques for vertebral body insufficiency fracture repair by analyzing
      restoration of height, strength, and stiffness, and quantifying cement leakage.
      SUMMARY OF BACKGROUND DATA: Current techniques for insufficiency fracture repair,
      restore prefracture strength, and all potentially have the complication of cement
      extrusion. To our knowledge, there is no information directly comparing different
      augmentation techniques. METHODS: There were 4 osteoporotic/osteopenic fresh
      cadaveric spines' (T6-L5) vertebral bodies divided into the 4 groups and by
      levels (thoracic, thoracolumbar, lumbar). They were compressed to 25% of their
      initial height to simulate insufficiency fractures. Fixation techniques were
      vertebroplasty, osteoplasty (Interpore Cross Int., Irvine, CA), the Cavity
      Creation System (Synthes, Paoli, PA), and kyphoplasty (Kyphon, Sunnyvale, CA).
      Fractures were fixed using 3 cc of bone cement and recompressed. RESULTS: No
      significant difference was found in strength, height restoration, or stiffness
      among techniques (P < 0.05). Stiffness was significantly different in the lumbar
      levels between initial and post-fixation measurements (P < 0.05). Cement
      extrusion of 1 mL was seen in 1 vertebroplasty specimen. CONCLUSIONS: The 4
      techniques equally restored strength and stiffness. No difference was seen in
      height restoration. Cement extrusion was significant in only 1 vertebral body,
      which may be attributable to the cement quantity.

PMID- 16816751
TI  - Agreement between surgeons and an independent panel with respect to surgical site
      fusion after single-level anterior cervical spine surgery: a prospective,
      multicenter study.
AB  - STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To assess the: (1)
      agreement between surgeon and independent review of fusion after single-level
      anterior cervical decompression and fusion, and (2) influence of surgeon
      impression of patient status on agreement. SUMMARY OF BACKGROUND DATA: Failure to
      achieve fusion can lead to poor functional outcome. Visual inspection of plain
      radiographs is used to assess fusion, but this assessment's reliability is not
      well understood. METHODS: Of 668 participants in the Cervical Spine Research
      Society Outcomes Study, 181 underwent single-level procedures. Three independent
      reviewers and each surgeon assessed fusion (i.e., radiographic trabecular
      bridging of the graft-vertebral body gap and absence of spinous process motion)
      on plain radiographs at 3 and 6 months after surgery. Agreement was evaluated
      with an intraclass correlation coefficient (ICC). The influence of surgeon
      impression of patient status on agreement was assessed with logistic regression
      analysis. RESULTS: Agreement was high among reviewers (ICC 0.822 to 0.892) but
      poor between reviewers and surgeons (ICC 0.308 to 0.484); disagreement was higher
      when the surgeon reported medical (odds ratio [OR] = 0.19, 95%; confidence
      interval [CI] 0.12, 0.30; P < 0.001), neurologic (OR = 0.13, 95% CI: 0.09, 0.21,
      P < 0.001), or functional (OR = 0.19, 95% CI: 0.12, 0.29, P < 0.001) improvement
      than when the surgeon did not report this improvement. CONCLUSIONS: The finding
      that surgeons and independent reviewers disagreed on fusion assessment highlights
      the need for objective and reproducible measures of fusion.

PMID- 16816752
TI  - Three-dimensional spinal and pelvic alignment in an asymptomatic population.
AB  - STUDY DESIGN: A 3-dimensional (3-D) analysis of asymptomatic spinal and pelvic
      alignment. OBJECTIVE: To obtain 3-D reference values of spinal and pelvic
      parameters, vertebral and intervertebral orientations. SUMMARY OF BACKGROUND
      DATA: Referential values of spine and pelvis alignment are essential for the
      assessment of posture and balance. However, only 2-D referential values have been
      reported using standing sagittal radiographs, and, to our knowledge, no 3-D
      referential values have been reported to date. METHODS: A biplanar radiographic
      technique was used to obtain the 3-D reconstruction of the spine and pelvis of 34
      asymptomatic standing subjects. The 3-D values were calculated for most of the
      spinal and pelvic parameters. In addition, 3-D vertebral and intervertebral
      orientations were computed, and the apical and junctional zones were
      investigated. RESULTS: As reported in 2-D, a large variability and particular
      correlations were observed for the 3-D spinal and pelvic parameters. However,
      significant differences were found between 3-D and 2-D values. The 3-D vertebral
      and intervertebral sagittal rotations showed specific features in the apical and
      junctional zones of the asymptomatic spine. CONCLUSION: These data may be used as
      3-D referential values of spinal and pelvic alignment.

PMID- 16816753
TI  - Comparison of the anatomical risk for vertebral artery injury associated with the
      C2-pedicle screw and atlantoaxial transarticular screw.
AB  - STUDY DESIGN: We evaluated the trajectories of atlantoaxial transarticular and C2
      pedicle screws in 3 dimensions using computerized tomography. OBJECTIVE: To
      compare the anatomic risk for vertebral artery injury associated with C2-pedicle
      and atlantoaxial transarticular screws. SUMMARY OF BACKGROUND DATA: The
      atlantoaxial fixation technique using C1-lateral mass screws combined with C2
      pedicle screws is considered a safer technique for preventing vertebral artery
      injury than atlantoaxial transarticular fixation. However, few reports have
      compared the anatomic risk of vertebral artery injury associated with C2-pedicle
      screws with that of transarticular screws. METHODS: A total of 62 consecutive
      patients with cervical lesions were evaluated using 3-dimensional images
      reconstructed by a computer-assisted navigation system. We compared the maximum
      possible diameters of the atlantoaxial transarticular screw and C2-pedicle screw
      trajectories, and examined whether the maximum possible diameters were limited by
      the height or width of the bony structure in screw trajectories < or = 4 mm in
      diameter. RESULTS: Mean maximum possible diameters did not differ significantly
      between the trajectories of 124 atlantoaxial transarticular and 124 C2-pedicle
      screws. In screw trajectories < or = 4 mm in diameter, 57.1% of transarticular
      screw trajectories were limited by the height of the bony structure, and all
      pedicle screw trajectories were limited by the width. CONCLUSIONS: C2-pedicle
      screw placement has nearly the same anatomic risk of vertebral artery injury as
      transarticular screw placement. Preoperative 3-dimensional evaluation may be
      useful for choosing the best surgical technique.

PMID- 16816754
TI  - The relationship between active and neural measures in patients with nonspecific
      low back pain.
AB  - STUDY DESIGN: Cross-sectional study of 50 individuals with nonspecific low back
      pain (LBP). OBJECTIVE: To evaluate the relationship between active and neural
      measurements in individuals with nonspecific LBP. SUMMARY OF BACKGROUND DATA: The
      Panjabi model for spinal stability consists of 3 interacting subsystems. Specific
      musculoskeletal measurements can be identified within the active and neural
      systems. The relationships among measures within this model have not been
      identified. METHODS: A total of 50 individuals with nonspecific LBP were
      evaluated for measures of the active and neural stability systems, and analyzed
      using a canonical correlation analysis, which is used to measure the relationship
      between 2 multidimensional variables. RESULTS: There were 2 significant
      relationships identified. The first identified a relationship among fatigue,
      flexion relation, and the feedforward abdominal response (r = 0.764, P < 0.001).
      The second relationship was between the Sorenson endurance test and feedforward
      abdominal response (r = 0.697, P = 0.006). CONCLUSION: Identification of
      relationships between back pain measurements may allow discrimination between
      individuals with different histology and pain levels. This process may assist the
      specificity of treatment programs prescribed for patients with back pain.

PMID- 16816756
TI  - Cost-effectiveness of two self-care interventions to reduce disability associated
      with back pain.
AB  - STUDY DESIGN: Two randomized, controlled trials. OBJECTIVE: To evaluate the
      incremental cost-effectiveness of psychologist-led and lay-led interventions in
      reducing disability in 2 cohorts of primary care patients with back pain. SUMMARY
      OF BACKGROUND DATA: Although activating self-care interventions have been
      advanced as effective tools to reduce back pain-related activity limitations, few
      studies have evaluated the added costs of these programs relative to their added
      benefits. METHODS: We estimated the incremental benefits and incremental costs
      associated with 2 self-care interventions for primary care patients with back
      pain. Effectiveness was measured as the number of low-impact back pain days
      (i.e., days when patients were satisfied with their level of back pain) over a 1
      year follow-up. Costs of back-pain related services were estimated from health
      plan cost data. Incremental cost-effectiveness ratios were calculated for each
      intervention to determine the costs associated with an additional low-impact back
      pain day. RESULTS: Patients assigned to the lay and psychologist interventions
      had a mean of 14.3 (95% confidence interval [CI] -2.7 to 30.9) and 26.2 (95% CI
      9.1-44.4) additional low-impact back pain days, respectively, compared with
      patients receiving usual care. The incremental per-person costs of the lay-led
      and psychologist-led interventions were dollar 139 (95% CI - dollar 62.13 to
      dollar 321.76) and dollar 161 (95% CI dollar 51.18 to dollar 275.93),
      respectively. The mean cost of an additional low-impact back pain day was dollar
      9.70 for the lay-led intervention and dollar 6.13 for the psychologist-led
      intervention. CONCLUSIONS: Both the lay and psychologist interventions were
      associated with modest improvements in outcomes but with somewhat higher costs
      compared to usual care.

PMID- 16816757
TI  - Postoperative analgesia after anterior correction of thoracic scoliosis: a
      prospective randomized study comparing continuous double epidural catheter
      technique with intravenous morphine.
AB  - STUDY DESIGN: Prospective randomized comparative study of two techniques for
      postoperative analgesia. OBJECTIVE: Assess the efficacy of two epidural catheters
      compared with intravenous morphine after anterior correction of thoracic
      scoliosis. SUMMARY OF BACKGROUND DATA: Spine surgery with anterior thoracotomy
      can cause severe postoperative pain. Continuous epidural analgesia through two
      epidural catheters was shown to be effective after posterior scoliosis
      correction. The efficacy of this technique has still not been demonstrated in
      this surgical context. METHODS: Thirty adolescent patients with thoracic
      idiopathic scoliosis scheduled for anterior correction were prospectively
      randomized into morphine (M) or epidural (E) group. In the E group, two epidural
      catheters were placed transforaminally after scoliosis correction. The immediate
      postoperative analgesia was performed with remifentanil in all patients until the
      first postoperative morning (T0 = begin of study), when either continuous
      intravenous morphine (M group) or continuous epidural ropivacaine 0.3% (E group)
      was initiated. Pain at rest and in motion, morphine consumption, sensory level,
      motor blockade, nausea/vomiting, pruritus, bowel function, and patient
      satisfaction were assessed. RESULTS: In the E group, there was significantly less
      pain at rest and in motion, less rescue morphine consumption, improved bowel
      activity, and higher patient satisfaction. The incidence of side effects was
      significantly higher in M group. CONCLUSIONS: Two epidural catheters provide
      better postoperative analgesia with fewer side effects and higher patient
      satisfaction after anterior instrumentation of thoracic scoliosis.

PMID- 16816758
TI  - A psycho-educational video used in the emergency department provides effective
      treatment for whiplash injuries.
AB  - STUDY DESIGN: Randomized control trial conducted between June 2000 and September
      2002. OBJECTIVE: To determine whether a short psycho-educational video shown in
      the Emergency Department shortly after the injury would produce follow-up pain
      reductions and reduced medical utilization. SUMMARY OF BACKGROUND DATA: Chronic
      pain following a whiplash injury is one example of the massive medical/legal
      problem of chronic muscular pain. Approaches using local pain sources (trigger
      points) have shown promise as treatment models for this type of pain. METHODS: 1)
      SETTING: Emergency Departments (ED) and urgent care (UC) facilities. 2) PATIENTS:
      126 patients entering EDs or UCs. 3) INTERVENTION: PATIENTS assigned to 12-minute
      video or care as usual. 4) MAIN OUTCOME MEASURES: Short Form Musculoskelatal
      Function Assessment (SMFA), phone questionnaires assessing: narcotics use, ER
      use, UC use, surgical consultations, etc. RESULTS AND CONCLUSIONS: PATIENTS
      viewing the video had dramatically lower pain ratings at a 1-month follow (6.09
      [10.6] vs. 21.23 [17.4], P < 0.001) and this pattern held for the 3- and 6-month
      follow-up period. Similarly, for 17 of 21 items asked at follow-up, the video
      group showed superior outcomes (chi2 ranged from 5 to 35, P < 0.05, all). For
      example, 4% of video patients were using narcotics at 6 month post ED visit
      compared with 36% of controls. The brief psycho-educational video had a profound
      effect on subsequent pain and medical utilization.

PMID- 16816759
TI  - Disc distraction shows evidence of regenerative potential in degenerated
      intervertebral discs as evaluated by protein expression, magnetic resonance
      imaging, and messenger ribonucleic acid expression analysis.
AB  - STUDY DESIGN: An animal model of degeneration was used to determine the effects
      of disc distraction, and was evaluated with magnetic resonance imaging (MRI) as
      well as gene and protein expression levels. OBJECTIVE: To investigate gene
      expression and MRI effects of distraction. SUMMARY OF BACKGROUND DATA: Disc
      degeneration can result from hyper-physiologic loading. Distracted discs with
      degeneration showed histologic signs of tissue recovery. METHODS: There were 18
      rabbits that underwent 28 days of compression (200 N) to induce moderate disc
      degeneration followed by 28 days of distraction (120 N; attached and loaded
      distraction device) or sham distraction (attached but unloaded distraction
      device). Comparison was performed with 56 days of compressed discs without
      distraction. Quantitative outcome measures were MRI signal intensity and gene
      expression analysis to determine: messenger ribonucleic acid levels for
      extracellular matrix genes, including collagen 1, collagen 2, biglycan, decorin,
      aggrecan, fibromodulin, and osteonectin; and matrix-regulative genes, including
      matrix metalloproteinase-13, tissue-inhibitor of matrix metalloproteinase-1, and
      bone morphogenetic protein (BMP)-2. Immunohistology was performed for collagen 2
      and BMP-2 to label cells semiquantitatively by staining of the cell-surrounding
      matrix. RESULTS: A total of 28 days of compression decreased signal intensity.
      Distraction over the same period reestablished physiologic signal intensity,
      however, a persistent reduction was found in sham distraction. Distraction
      resulted in gene expression up-regulation of collagen 1 (5.4-fold), collagen 2
      (5.5-fold), biglycan (7.7-fold), and decorin (3.4-fold), while expression of
      fibromodulin (0.16-fold), tissue-inhibitor of matrix metalloproteinase-1 (0.05
      fold), and BMP-2 (0.15-fold) was decreased, as compared with 56 days compression.
      Distracted discs showed more BMP-2 (19.67 vs. 3.67 in 56 days compression) and
      collagen 2 (18.67 vs. 11.33 in 56 days compression) positive cells per field.
      CONCLUSIONS: Distraction results in disc rehydration, stimulated extracellular
      matrix gene expression, and increased numbers of protein-expressing cells.

PMID- 16816760
TI  - Porous coated motion cervical disc replacement: a biomechanical,
      histomorphometric, and biologic wear analysis in a caprine model.
AB  - STUDY DESIGN: The biomechanical, histopathologic, and histomorphometric
      characteristics of cervical disc replacement were assessed in a caprine animal
      model. OBJECTIVE: To investigate the biomechanical, porous ingrowth, and
      histopathologic characteristics of the Porous Coated Motion (PCM) Cervical Disc
      replacement (Cervitech, Inc., Rockaway, NJ). SUMMARY OF BACKGROUND DATA: As an
      alternative to anterior cervical interbody arthrodesis, an artificial cervical
      disc serves to replace the symptomatic degenerated disc, restore the functional
      biomechanical properties of the motion segment, and preserve neurologic function.
      METHODS: There were 12 mature Nubian goats divided into 2 groups based on
      postoperative survival periods of 6 (n = 6) and 12 months (n = 6). Using an
      anterior surgical approach, a complete discectomy was performed at the C3-C4,
      followed by implantation of the PCM device. Functional outcomes of the disc
      prosthesis were based on computerized tomography (CT), multidirectional
      flexibility testing, undecalcified histology, histomorphometric, and
      immunocytochemical analyses. RESULTS: There was no evidence of prosthesis
      loosening, or neurologic or vascular complications. CT showed the ability to
      image and assess the cervical spinal canal for the presence of compressive
      pathology in the area of the CoCrMo prosthesis. Multidirectional flexibility
      testing under axial rotation and lateral bending indicated no differences in the
      full range of intervertebral motion between the disc prosthesis and nonoperative
      controls (P > 0.05). Based on immunohistochemical and histologic analysis, there
      was no evidence of particulate debris, cytokines, or cellular apoptosis within
      the local or systemic tissues. Moreover, review of the spinal cord at the
      operative levels indicated no evidence of cord lesions, inflammatory reaction,
      wear particles, or significant pathologic changes in any treatment.
      Histomorphometric analysis at the metal-bone interface indicated the mean
      trabecular ingrowth of 40.5% +/- 24.4% and 58.65% +/- 28.04% for the 6 and 12
      month treatments, respectively. CONCLUSION: To our knowledge, this serves as the
      first in vivo time-course study investigating the use of the PCM device for
      cervical arthroplasty. All 12 animals undergoing cervical disc replacement had no
      evidence of implant loosening, subluxation, or inflammatory reactions. PCM
      cervical arthroplasty permits unobstructed visualization of the spinal canal
      based on CT imaging. Segmental intervertebral motion was preserved under axial
      rotation and lateral bending loading conditions, while at the same time
      permitting porous osseointegration at the prosthesis-bone interface. Based on
      histopathologic review of all local and systemic tissues, there was no evidence
      of particulate wear debris, cytokines, cellular apoptosis, or significant
      pathologic changes in any treatment.

PMID- 16816761
TI  - In vivo temperature profile of intervertebral discs and vertebral endplates
      during vertebroplasty: an experimental study in sheep.
AB  - STUDY DESIGN: Experimental study of temperature profiles during vertebroplasty.
      OBJECTIVES: To define accurate temperature profiles during vertebroplasty in an
      in vivo animal model. SUMMARY OF BACKGROUND DATA: Controversy still exists
      whether vertebroplasty achieves its analgesic effect by stabilizing fracture
      fragments or due to thermal damage of sensory nerves inside the vertebral body.
      Furthermore, the energy release during cement polymerization may cause thermal
      injury to the spinal cord or intervertebral discs. METHODS: A total of 4.0 mL
      PMMA was injected into three lumbar vertebrae of four skeletally mature mixed
      bred ewes. Nine separate K-type thermocouples were placed into 12 vertebrae and
      their adjacent intervertebral discs. Temperature changes were recorded
      continuously before, during, and after the injection. RESULTS: The highest peak
      temperatures were measured at the cranial endplate (mean 42.4 +/- 8.8 C) and in
      the center of the vertebral body (mean 43.3 +/- 6.9 C). Temperatures stayed above
      40 C for approximately 2.5 minutes. Peak temperatures in the discs and at the
      dorsal wall (closest to spinal cord) did not exceed 41 C and 47 C and stayed
      above 40 C for approximately 1.5 minutes. CONCLUSIONS: The intervertebral discs
      and the spinal cord do not seem to be in danger of thermal damage during
      vertebroplasty. The measured energy does not seem to be sufficient for the
      palliative effect achieved by vertebroplasty.

PMID- 16816763
TI  - The effects of rod contouring on spinal construct fatigue strength.
AB  - STUDY DESIGN: In vitro fatigue loading using a corpectomy model outfitted with
      posterior pedicle screw instrumentation. OBJECTIVE: The purpose of this study was
      to detect differences in fatigue resistance of titanium and stainless steel
      spinal constructs that use rods contoured using a French Bender, and to compare
      differences in fatigue resistance of contoured and straight titanium rods.
      SUMMARY OF BACKGROUND DATA: Instrumentation failure is generally thought to be
      caused by fatigue or cyclic loading. Intraoperative contouring of the posterior
      rods is almost always required to match the native kyphotic (thoracic) or
      lordotic (cervical or lumbar) spinal curvature. How bending these rods affects
      their overall fatigue resistance is not well described. In addition, changes in
      fatigue resistance may be a function of material type. METHODS: Spinal constructs
      were evaluated using the ASTM F1717-01 model. Two different titanium-based rods
      (Ti6AL4V and CpTi) and two different steel-based rods (Orthinox and 316L
      stainless steel) were evaluated in this study (n = 6 for each group). Rods were
      contoured at two points using a French Bender and were rigidly coupled to
      polyaxial pedicle screws within UHMWPE vertebral bodies. Constructs were cycled
      at a load ratio of 10 between a minimum and maximum loading regime of -250 N/-25
      N and -700 N/-70 N at a frequency of 4 Hz. Estimated maximum nominal stresses at
      various points of interest in the spinal constructs were calculated using beam
      theory. Effects of the rod material, load, and stress on the number of cycles to
      failure were analyzed using Cox proportional hazards regression. RESULTS: All of
      the spinal constructs with contoured CpTi rods and contoured Ti6Al4V rods failed
      at one of the bends in the rods. Almost all of the spinal constructs with
      straight CpTi rods and straight Ti6Al4V rods failed where the blocker screw
      fastens the rod to the coupler of the polyaxial screw head. Contoured titanium
      constructs demonstrated significantly lower fatigue life than contoured 316L
      constructs. Contouring tended to lower the fatigue life of both the Ti6Al4V and
      CpTi constructs. CONCLUSION: Intraoperative rod contouring using a French Bender
      significantly reduces the fatigue life of titanium spinal constructs.

PMID- 16816764
TI  - The effect of anterior cervical fusion on neck motion.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To precisely measure the
      effect of anterior cervical fusion on neck motion. SUMMARY OF BACKGROUND DATA:
      Anterior cervical decompression and stabilization procedures are successful in
      treating recalcitrant cervical radiculopathy and cervical myelopathy. Most assume
      that these "fusion" procedures result in a loss of neck motion, although changes
      in overall motion following anterior cervical fusion have never been precisely
      quantified. METHODS: Twenty-five consecutive patients undergoing anterior
      cervical fusion of one to four levels underwent cervical range of motion testing
      in three planes using an unconstrained instrumented linkage before surgery and
      more than 3 months after surgery. These data were compared with that of 10
      volunteers with no prior history of neck complaints. Motion data were compared
      between patients and volunteers, and between the patients before surgery and at
      last follow-up, using RMANOVA and Fisher's PLSD post hoc test. RESULTS: Before
      surgery, the patients had significantly less motion than the volunteers in all
      directions. Following surgical fusion, patients gained a statistically
      significant amount of motion in all planes, although they did not achieve the
      motion seen among the volunteers. Gains in motion were seen among all patients,
      including those undergoing four-level fusions, and there was no correlation
      between postoperative motion and the number of levels fused. CONCLUSIONS:
      Patients undergoing anterior cervical fusion have diminished neck motion compared
      with normal volunteers. Following surgery, they may be expected to gain motion,
      even when undergoing multilevel fusions. However, these patients are unlikely to
      regain the neck motion seen among normal individuals without neck complaints.

PMID- 16816765
TI  - Clinical and radiologic 2-4-year results of transforaminal lumbar interbody
      fusion in degenerative and isthmic spondylolisthesis grades 1 and 2.
AB  - STUDY DESIGN: Prospective clinical study. OBJECTIVE: To evaluate the clinical and
      radiographic result of the transforaminal lumbar interbody fusion (TLIF) as an
      alternative new technique in degenerative and isthmic lower grade
      spondylolisthesis. SUMMARY OF BACKGROUND DATA: TLIF is a new alternative surgical
      technique used for spinal fusion avoiding the ventral approach and can
      theoretically prevent typical complications, such as those seen in anterior and
      posterior lumbar interbody fusion. MATERIALS AND METHODS: There were 19
      degenerative, 19 isthmic, and 1 dysplastic spondylolistheses operated on with
      TLIF. The clinical follow-up used the Oswestry Disability Index, the radiologic
      follow-up radiograph, analyzing segmental lordosis, intervertebral space,
      reduction, and fusion rate. The minimum follow-up was 24 months, mean clinical
      follow-up was 50 months, and radiologic follow-up was 35 months. RESULTS: The
      medium of the Oswestry Disability Index in all patients decreased from 23.5 to
      13.5 points, in isthmic spondylolistheses from 20.5 to 10.95 after 2 years. The
      radiographic fusion rate was 94.8%. The sagittal translation was reduced from 23%
      to 15%. There were 3 (7.6%) serious postoperative complications observed, which
      required operative revision. CONCLUSIONS: TLIF is a safe and effective method to
      treat low-grade spondylolisthesis, which can theoretically prevent typical
      complications of anterior and posterior lumbar interbody fusion. The results of
      isthmic spondylolistheses were significantly better compared to degenerative
      spondylolistheses.

PMID- 16816766
TI  - Predictors of outcome in patients with (sub)acute low back pain differ across
      treatment groups.
AB  - STUDY DESIGN: Prospective study with 6 weeks of follow-up. OBJECTIVE: To examine
      the predictors of outcome for patients with (sub)acute low back pain (LBP)
      receiving usual care (UC) or a minimal intervention strategy (MIS) aimed at
      psychosocial factors. SUMMARY OF BACKGROUND DATA: A randomized controlled trial
      in general practice showed no differences in average effect between UC and MIS.
      METHODS: Socio-demographic variables, characteristics of LBP, and psychosocial
      factors were included as potential predictors of outcome. The outcome clinically
      important improvement was defined as a reduction of at least 30% on functional
      disability plus patient perceived recovery. Logistic regression analyses were
      used to study the associations between predictors and outcome at 6 weeks follow
      up. RESULTS: In the UC group (n = 163), the multivariable model included a
      shorter duration of the LBP episode, few previous episodes, less pain
      catastrophizing, and good perceived general health. The area under the curve
      (AUC) of the model was 0.77 (95% confidence interval, 0.70-0.85). In the MIS
      group (n = 142), the multivariable model included less somatizing symptoms, more
      solicitous responses by an important other, lower perceived risk for chronic LBP,
      more fear avoidance beliefs, higher level of education, and shorter duration of
      the LBP episode. This AUC was 0.78 (95% confidence interval, 0.71-0.86).
      CONCLUSIONS: As we found two different profiles, our approach may contribute to
      the important question: what intervention works for whom?

PMID- 16816767
TI  - The position of the aorta relative to the spine before and after anterior
      instrumentation in right thoracic scoliosis.
AB  - STUDY DESIGN: Preoperative magnetic resonance images (MRI) and postoperative
      axial computed tomography (CT) scans in 25 consecutive patients with idiopathic
      right thoracic adolescent scoliosis (AIS) and anterior correction and fusion with
      a dual rod system were analyzed in a prospective study. OBJECTIVES: Evaluation of
      the spatial relations between the vertebral body and the aorta and the relative
      migration of the aorta due to the anterior correction and instrumentation in
      right thoracic scoliosis patients. SUMMARY OF BACKGROUND DATA: In anterior
      scoliosis surgery, bicortical screw purchase is performed to increase pullout
      strength. However, impingement of the aorta due to excessive contralateral screw
      penetration has been reported, especially after endoscopic instrumentation. For a
      safe screw placement, knowledge of both the preoperative topographic relation of
      aorta and vertebral body and its changes due to surgical correction is crucial.
      Recent studies reported on a more lateral and posterior position of the aorta in
      AIS patients. However, there are hardly any data on the changes of the aortic
      position after anterior curve correction available in the current literature.
      METHODS: All 25 patients underwent an identical anterior surgical technique with
      standard open approach and dual rod instrumentation of the primary curve.
      Preoperative MRI and postoperative sequential CT scans of 180 vertebrae were
      analyzed with respect to following parameters: vertebral body width and depth,
      diameter of the aorta, closest distance between aorta and the vertebral body, the
      aorta-vertebral angle, and the position of the aorta in relation to the spinal
      canal. RESULTS: Before surgery, the aorta is positioned posterolaterally with an
      aorta-vertebral angle of between 78 degrees and 92 degrees (between T5 and T10).
      Between T11 and L2, the aorta is positioned more anteromedially with an aorta
      vertebral angle from 62 degrees (T11) to 16 degrees (L2). After surgery, the
      aorta has migrated from a posterolateral to a more anteromedial position. This
      migration is maximal at the apex vertebra with an average change of the aorta
      vertebral angle of 31.4 degrees . Whereas the distance between the aorta and the
      vertebral body increases at the upper and lower fusion levels, the aorta moves
      significantly closer to the vertebral body at the curve apex due to surgical
      correction. In patients with thoracic hypokyphosis, the aorta is positioned
      significantly more posterior than in patients with hyperkyphosis. CONCLUSIONS:
      This MRI and CT based study of 25 patients with thoracic AIS treated by standard
      open dual rod and dual screw instrumentation demonstrates a migration of the
      aorta by 31 degrees from a more posterolateral position before surgery to a more
      anteromedial position after surgery at the curve apex. Scoliosis surgeons should
      be aware of these changes; any excessive contralateral screw penetration must be
      avoided at any level.

PMID- 16816768
TI  - A three-year follow-up of lumbar spine endplate (Modic) changes.
AB  - STUDY DESIGN: A longitudinal follow-up of Modic changes on magnetic resonance
      imaging (MRI). OBJECTIVES: To assess the prevalence and natural course Modic
      changes over a 3-year follow-up period. SUMMARY OF BACKGROUND DATA: Modic changes
      are bone marrow and endplate lesions visible on MRI. To the authors' knowledge,
      no follow-up studies on their natural course have been published. METHODS: The
      study population consisted of 60 unoperated sciatica patients 23 to 76 years of
      age. Baseline and 3-year lumbar MR images from L1-L2 through L5-S1 were analyzed
      independently by 2 radiologists and a consensus reading was performed. RESULTS:
      At baseline, the prevalence of Modic changes was 23%. Seven discs had mixed Type
      I/II, and 63 Type II change. Changes typically occurred at L4-L5 and L5-S1, and
      associated positively with age (P = 0.009). Ten of 70 discs (14%) with Modic
      changes at baseline displayed another type at 3 years. Furthermore, the
      nonconverted changes increased significantly in size. The incidence of new Modic
      changes during the follow-up was 6% (13 of 230). CONCLUSIONS: Modic changes are
      common MRI findings in patients with degenerative lumbar disc disease. We found
      evidence that Modic Type II changes may be less stable than previously assumed.

PMID- 16816769
TI  - Interobserver and intraobserver reliability of maximum canal compromise and
      spinal cord compression for evaluation of acute traumatic cervical spinal cord
      injury.
AB  - STUDY DESIGN: Prospective, blinded validation study of an objective, quantitative
      measure to assess maximum canal compromise (MCC) and maximum spinal cord
      compression (MSCC) in individuals with acute cervical spinal cord injury (SCI).
      OBJECTIVE: To examine the intraobserver and interobserver reliability of MCC and
      MSCC in individuals with acute traumatic cervical SCI. SUMMARY OF BACKGROUND
      DATA: To date, few quantitative reliable radiologic methods for assessing the
      extent of spinal cord compression in the setting of acute SCI have been reported.
      MCC and MSCC, as assessed on mid-sagittal CT and T2-weighted MR images,
      respectively, appear to have potential clinical and prognostic value. To date,
      the validation of these assessment tools has been limited to a small number of
      observers at a single institution. However, to date no study has focused on the
      reliability of these radiologic parameters among a large cohort of spine surgeons
      from North America and abroad. This type of validation is critical to allow the
      broader use of these outcome measures in research studies and in clinical
      practice. METHODS: Mid-sagittal MRI and CT images of cervical spine were selected
      from 10 individuals with acute traumatic cervical SCI. A total of 28 spine
      surgeons independently estimated CT MCC, T1-weighted MRI MCC, and T2-weighted MRI
      MSCC on two occasions using a calibrated ruler. In the first round of
      measurements, the observers estimated the radiologic parameters using only
      written instructions. The second measurement set was obtained after an
      interactive teaching session on the methodology. The order of the images was
      altered for the second set of measurements. RESULTS: Analysis using parametric
      and nonparametric statistics indicated high intraobserver reliability for CT MCC,
      T1-weighted MRI MCC, and T2-weighted MSCC with interclass correlation
      coefficients (ICCs) of 0.92, 0.95, and 0.97, respectively. The interobserver
      reliability for all three radiologic parameters was considered moderate with ICCs
      ranging from 0.35 to 0.56. CONCLUSION: Our results indicate that the
      intraobserver reliability for the MCC and MSCC was high. Although the
      interobserver reliability for all three radiologic parameters in the present
      study was below 0.75, the observed differences were small and largely accounted
      for by the limitations in the precision of the calibrated ruler. For cases with
      minimal cord compression, the measurement of canal stenosis (MCC) proved more
      accurate. In contrast, in cases with severe cord compression, the assessment of
      MSCC was more accurate. It is anticipated that the use of digital imaging
      technologies will further enhance the precision of these outcome measures.

PMID- 16816770
TI  - Mobility of lumbar segments instrumented with a ProDisc II prosthesis: a two-year
      follow-up study.
AB  - STUDY DESIGN: Longitudinal prospective study on a sample of 41 consecutive disc
      prosthesis patients, covering a postoperative time period of at least 2 years.
      OBJECTIVES: To document the rotational and translational range of segmental
      motion of patients instrumented with ProDisc II prostheses in the lumbar spine
      and to compare motion between instrumented and untreated adjacent segments with
      respect to a normative database. To discuss potential causes of the low range of
      rotational motion observed after instrumentation with a Prodisc II prosthesis.
      SUMMARY OF BACKGROUND DATA: Disc replacement is intended to restore physiologic
      motion and height of the affected levels. Published reports show, however, that
      the goal of restoring motion at the operated segment is missed in the majority of
      cases. The cause of this failure is unresolved. METHODS: Rotational and
      translational segmental motion in the sagittal plane, disc height, and
      posteroanterior displacement were measured from lateral radiographic views taken
      standing (before surgery) and in flexion and extension (1 year and 2 years after
      surgery) by Distortion Compensated Roentgen Analysis (DCRA). The protocol permits
      to take measurements from all segments imaged on the radiographic views and
      compensates for variations in stature, magnification, and posture. Data from
      instrumented and untreated segments can be compared and related to a previously
      determined normative database. RESULTS: The rotational range of motion of
      segments instrumented with a ProDisc II prosthesis was low, especially at L4-L5
      and L5-S1. In the majority of cases, it amounted to less than 45% of the normal
      range. Virtually no improvement occurred between 1 and 2 years after surgery.
      Malalignment of the axis of rotation of the prosthesis with respect to the
      anatomic axis, persisting clinical symptoms, or the significant increase of
      intervertebral space documented after instrumentation are unlikely to cause the
      low range of motion. As the range of rotational motion of the untreated segments
      was low with respect to normal as well, it is conjectured that tissue adaptation
      during the preoperative symptomatic time period might have caused the
      postoperative motion deficit. This conjecture complies with fragmentary previous
      observations of a low postoperative segmental range of motion from untreated
      segments of fusion patients. CONCLUSIONS: Disc replacement in the lumbar spine by
      a ProDisc II implant fails to restore normal segmental rotational motion in the
      sagittal plane, specifically at levels L4-L5 and L5-S1. As segmental motion of
      the untreated segments was lower than normal as well, though not quite as
      conspicuous as that of instrumented segments, adaptation of soft tissue taken
      place during the preoperative symptomatic time period is conjectured to cause the
      observed motion deficit. Postoperative physical therapy might be considered if
      restoration of a normal range of rotational motion is desired.

PMID- 16816771
TI  - Screw position after double-rod anterior spinal fusion in idiopathic scoliosis:
      an evaluation using computerized tomography.
AB  - STUDY DESIGN: A retrospective evaluation of screw position after double-rod
      anterior spinal fusion in idiopathic scoliosis using computerized tomography
      (CT). OBJECTIVE: To evaluate screw position and complications related to screw
      position after double-rod anterior instrumentation in idiopathic scoliosis.
      SUMMARY OF BACKGROUND DATA: Anterior instrumentation and fusion in idiopathic
      scoliosis is gaining widespread use. However, no studies have been published
      regarding the accuracy of screw placement and screw-related complications in
      double-rod and double-screw anterior spinal fusion and instrumentation in
      idiopathic thoracolumbar scoliosis surgery. METHODS: CT examinations were
      performed after surgery in 17 patients with idiopathic scoliosis. At each
      instrumented level, the position of the screw and the plate relative to the
      spinal canal, relative to the neural foramen, and relative to the aorta was
      measured. Complications related to screw position were registered. RESULTS: A
      total of 189 screws in 17 patients were evaluated. Malposition occurred in 23%
      (16 patients) of the total number of screws. Three screws (2 patients) were
      partially in the spinal canal (1%). This resulted in pain in the right leg in 2
      patients. However, electromyography showed no abnormalities. At three levels (3
      patients), there was contact between the instrumentation and the aorta. However,
      no vascular complications occurred. A total of 113 screws (10 patients) were
      placed under fluoroscopic control and 76 screws (7 patients) were placed without
      use of fluoroscopy. Less screw malposition was observed in the group in which
      fluoroscopic control was used (19% vs. 30%, not significant). CONCLUSIONS: Screw
      placement in double-rod anterior spinal fusion in idiopathic scoliosis seems to
      be technically demanding, and the use of fluoroscopic control results in less
      frequent malposition. The risk of neurologic and vascular complications is low.

PMID- 16816772
TI  - Association between back pain and physical fitness in adolescents.
AB  - STUDY DESIGN: A cross-sectional study of 9413 adolescents. OBJECTIVES: To study
      the associations between back pain, physical activity, and physical fitness.
      SUMMARY OF BACKGROUND DATA: A high physical fitness level, and especially muscle
      endurance in the back muscles, is associated with lower risk of back pain, but
      little is known about other types of physical fitness and back pain in
      adolescents. METHODS: A cross-sectional study of 3956 boys and 5457 girls 17
      years of age. The associations between self-reported back pain and different
      types of physical fitness and self-reported physical activity were analyzed in
      high schoolchildren in Denmark. RESULTS: Back pain was reported by 43% of the
      girls and 37% of the boys. Back pain was associated with low isometric muscle
      endurance in the back extensors, and the highest quartile had a lower risk of
      back pain (odds ratio = 0.71; 95% confidence interval, 0.62-0.82) within the last
      month. No associations were found to aerobic fitness, functional strength,
      flexibility, or physical activity level after adjustment for muscle endurance.
      More girls than boys experienced back pain, and it was more common in taller
      adolescents. CONCLUSION: Children with high isometric muscle endurance were less
      likely to report back pain. No other measures of physical fitness or level of
      self-reported physical activity were linked to back pain reporting.

PMID- 16816773
TI  - Thoracolumbar hemivertebrae resection by double approach in a single procedure:
      long-term follow-up.
AB  - STUDY DESIGN: Retrospective review of patients records with clinical and
      radiographic assessment. OBJECTIVE: To evaluate the long-term result of
      thoracolumbar hemivertebrae resection using a double approach in a single
      procedure. SUMMARY OF BACKGROUND DATA: Thoracolumbar hemivertebrae resection by a
      combined posterior and anterior approach has been previously described, but this
      is the largest series of hemivertebrae reported. METHODS: From 1987 to 2003, a
      consecutive series of 34 congenital scoliosis or kyphoscoliosis due to
      thoracolumbar hemivertebrae were managed by hemivertebra resection using a
      combined posterior and anterior approach and short anterior and posterior convex
      fusion in the same day/same anesthesia. RESULTS: The mean age at surgery was 3.5
      years. The mean follow-up period was 6.0 years. There was a mean improvement of
      69.3% in the segmental curve from a mean angle of 34.8 degrees before surgery to
      10.7 degrees at the latest follow-up assessment. The global scoliosis curve
      improved of 33.4% from 40.4 degrees to 26.9 degrees, respectively. Trunk shift
      was significantly improved. The mean final kyphosis was within normal values.
      CONCLUSIONS: This procedure is safe and offers a persistent correction with a
      short segment fusion. Surgery should be performed as early as possible to avert
      severe local deformities and prevent secondary structural deformities in order to
      avoid extensive fusions.

PMID- 16816774
TI  - Re: Lowe TG, Wilson L, Chien JT, et al. A posterior tether for fusionless
      modulation of sagittal plane growth in a sheep model. Spine 2005;30:S69-S74.

PMID- 16816775
TI  - Re: Asher MA, Lai SM, Glattes RC, et al. Refinement of the SRS-22 questionnaire
      Function domain. Spine 2006;31:593-597.

PMID- 16816777
TI  - Clinical assessment of suicide risk in depressive disorder.
AB  - Efforts to identify clinical risk factors for complete suicide through the follow
      up of depressed patients have yielded relatively few robust predictors. Those
      identified by at least three studies are (in order of decreasing frequency)
      suicidal plans/attempts, male sex, being single or living alone, inpatient
      status, and hopelessness. Because the best established of these predictors has
      only modest sensitivity and specificity, the need for other robust tools is
      clear. A rich body of research has identified two biological risk factors for
      suicide in depressive disorder: hypothalamic-pituitary-adrenal axis hyperactivity
      and deficits in serotonin function. Moreover, there is now considerable evidence
      that the dexamethasone suppression test and measures of serum cholesterol
      concentrations, respectively, may provide a clinically useful reflection of these
      two mechanisms. Observations that these measures appear to be additive, both with
      each other and with other clinical risk factors, indicate that a substantial
      improvement in the clinician's ability to assess suicide risk is possible.

PMID- 16816778
TI  - Addressing suicide and its risk.

PMID- 16816779
TI  - Beauty and the beast: Psychobiologic and evolutionary perspectives on body
      dysmorphic disorder.
AB  - Body dysmorphic disorder (BDD) is characterized by preoccupation with a defect in
      appearance. Concepts of beauty play a particularly crucial role in humans' mental
      and social life, and may have specific psychobiologic and evolutionary
      underpinnings. In particular, there is a growing literature on the neurocircuitry
      underpinning the body schema, body image and facial expression processing, and
      aesthetic and symmetry judgments. Speculatively, disruptions in cognitive
      affective processes relevant to judgements about physical beauty lead to BDD.

PMID- 16816780
TI  - Syndrome of inappropriate antidiuretic hormone associated with escitalopram
      therapy.
AB  - Escitalopram is the selective serotonin reuptake inhibitor (SSRI) most recently
      approved for use in the United States. It is structurally related to citalopram,
      but is felt to have a more tolerable side-effect profile than its parent
      compound. Side effects are not generally serious and include headache, diarrhea,
      and nausea. While hyponatremia and the syndrome of inappropriate antidiuretic
      hormone (SIADH) have been associated with treatment with other SSRIs, there has
      only been one case of escitalopram-induced SIADH reported in the literature to
      date. We now report another case of a patient who developed SIADH after being
      treated with escitalopram for 4 weeks. The patient's hyponatremia improved
      following the discontinuation of escitalopram. Clinicians should be aware of this
      uncommon but significant side effect of SSRIs and monitor high-risk patients for
      the development of SIADH.

PMID- 16816781
TI  - Aripiprazole-related tardive dyskinesia.
AB  - The low prevalence of extrapyramidal symptoms associated with atypical
      antipsychotics has led to their widespread use during the past decade.
      Aripiprazole, the newest medication in this class, has been associated with
      extrapyramidal symptoms (eg, akathisia) and with improvement of tardive
      dyskinesia (TD), but to date it has not been associated with the development of
      TD. We report a case of TD associated with the use of aripiprazole 15 mg/day for
      18 months for refractory depression. Symptoms of TD resolved within several weeks
      of discontinuation of aripiprazole.

PMID- 16816782
TI  - What has clinical research in suicide prevention done for you lately?

PMID- 16816783
TI  - The standard of care in suicide risk assessment: An elusive concept.
AB  - Suicide risk assessment is now a core competency requirement in the residency
      training of psychiatrists. The purpose of suicide risk assessment is to identify
      modifiable or treatable acute, high-risk suicide factors, and available
      protective factors that inform patient treatment and safety management. The
      standard of care varies according to state statutory definitions. Heretofore,
      most states adopted an average physician or "ordinarily employed standard."
      Currently, more states are adopting a "reasonable, prudent physician" standard.
      No single source or authority defines the standard of care for suicide risk
      assessment. Evidence-based psychiatry can inform clinicians' suicide risk
      assessments. Carefully documented risk assessments will assist the courts in
      evaluating clinicians' decision-making process.

PMID- 16816784
TI  - Application of The APA Practice Guidelines on Suicide to Clinical Practice.
AB  - This article presents charts from The American Psychiatric Association Practice
      Guideline for the Assessment and Treatment of Patients with Suicidal Behaviors,
      part of the Practice Guidelines for the Treatment of Psychiatric Disorders
      Compendium, and a summary of the assessment information in a format that can be
      used in routine clinical practice. Four steps in the assessment process are
      presented: the use of a thorough psychiatric examination to obtain information
      about the patient's current presentation, history, diagnosis, and to recognize
      suicide risk factors therein; the necessity of asking very specific questions
      about suicidal ideation, intent, plans, and attempts; the process of making an
      estimation of the patient's level of suicide risk is explained; and the use of
      modifiable risk and protective factors as the basis for treatment planning is
      demonstrated. Case reports are used to clarify use of each step in this process.

PMID- 16816785
TI  - Suicide in bipolar disorder: Risks and management.
AB  - Bipolar disorders are prevalent, often severe, and disabling illnesses with
      elevated lethality largely due to suicide. Suicide rates average approximately 1%
      annually, or perhaps 60 times higher than the international population rate of
      0.015% annually. Suicidal acts typically occur early in bipolar disorders and in
      association with severe depressive or mixed states. The high lethality of
      suicidal acts in bipolar disorders is suggested by a much lower ratio of
      attempts:suicide (approximately 3:1) than in the general population
      (approximately 30:1). Risk factors can help to identify patients at increased
      suicidal risk, but ongoing clinical assessment is essential to limit risk.
      Empirical short-term interventions to manage acute suicidal risk include close
      clinical supervision, rapid hospitalization, and electroconvulsive therapy.
      Remarkably, however, evidence of the long-term effectiveness of most treatments
      against suicidal behavior is rare. A notable exception is lithium prophylaxis,
      which is associated with consistent evidence of major (approximately 80%),
      sustained relative reductions of risk of suicides and attempts, and lower
      lethality (increased attempts:suicide ratio). Such benefits are unproved for
      other treatments commonly used to treat bipolar disorder patients, including
      anticonvulsants, antipsychotics, antidepressants, and psychosocial interventions.
      Applying available knowledge systematically, with close and sustained clinical
      supervision, can enhance management of suicidal risk in bipolar disorders
      patients.

PMID- 16816786
TI  - Defining and diagnosing involuntary emotional expression disorder.
AB  - Uncontrollable episodes of emotional expression occur in a variety of
      neurological conditions. This emotional disinhibition syndrome is characterized
      by episodes of crying or laughing that are unrelated to or out of proportion to
      the eliciting stimulus. This syndrome is common among patients with amyotrophic
      lateral sclerosis, multiple sclerosis, stroke, and traumatic brain injury and a
      variety of terms and definitions have been used to describe it. The confusing
      nomenclature has been a barrier to understanding, diagnosis, and treatment of
      this disorder. The authors propose a unifying term, involuntary emotional
      expression disorder (IEED), and provide diagnostic criteria for this disorder.

PMID- 16816787
TI  - More to movement disorders than motion.

PMID- 16816788
TI  - Insight in body dysmorphic disorder with and without comorbid obsessive
      compulsive disorder.
AB  - INTRODUCTION: The aim of this study was to compare the level of insight in
      patients with body dysmorphic disorder (BDD) with and without comorbid obsessive
      compulsive disorder (OCD), and to measure its possible relationships with
      clinical features. METHODS: Thirty outpatients affected by BDD, according to
      Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria, of
      whom 18 were also suffering from OCD, were included in the study. Clinical
      assessment was carried out by means of the Yale-Brown Obsessive-Compulsive Scale
      modified for BDD and a specially designed OCD Questionnaire. The level of insight
      was measured by means of the score at item 11 of the Yale-Brown Obsessive
      Compulsive Scale modified for BDD. RESULTS: The insight resulted to be excellent
      in four cases, good in four, fair in five, poor in 15 and absent in two.
      Significant and positive correlations were observed between the level of insight
      and the following items: resistance to thoughts and to activities as well as to
      time spent on activities and control on activities related to the defect. The
      insight was significantly lower in patients affected by both BDD and OCD.
      CONCLUSION: The findings indicate that the majority of BDD patients in this
      study, and especially those with comorbid OCD, have a low degree of insight that
      is significantly correlated to symptoms specific of the disorder.

PMID- 16816790
TI  - Psychogenic tremor: long-term outcome.
AB  - INTRODUCTION: Psychogenic disorders, also referred to as somatoform, conversion,
      somatization, hysteria, and medically unexplained symptoms, are among the most
      challenging disorders to diagnose and treat. Psychogenic movement disorders are
      increasingly encountered in specialized clinics, and represent approximately 15%
      of all patients evaluated in the Baylor College of Medicine Movement Disorders
      Clinic. OBJECTIVE: To characterize psychogenic tremor and provide data on
      prognosis and long-term outcome in a large group of patients with psychogenic
      tremor followed in a movement disorders clinic. METHODS: Patients evaluated at
      the Baylor College of Medicine Movement Disorders Clinic in Houston, Texas,
      between 1990 and 2003 with the diagnosis of psychogenic movement disorder (PMD),
      who consented to be interviewed, were administered a structured questionnaire
      designed to assess current motor and psychological function. RESULTS: psychogenic
      tremor is the most common PMD, accounting for 4.1% of all patients evaluated in
      our clinic. We were able to obtain clinical information on a total of 228 of 517
      (44.1%) patients with PMD, followed for a mean of 3.4+/-2.8 years. Among the 127
      patients diagnosed with psychogenic tremor, 92 (72.4%) were female, the mean age
      at initial evaluation was 43.7+/-14.1 years, and the mean duration of symptoms
      was 4.6+/-7.6 years. The following clinical features were considered to be
      characteristic of psychogenic tremor: abrupt onset (78.7%), distractibility
      (72.4%), variable amplitude and frequency (62.2%), intermittent occurrence
      (35.4%), inconsistent movement (29.9%), and variable direction (17.3%).
      Assessment of long-term outcome showed that 56.6% of patients reported
      improvement in their tremor. Factors predictable of a favorable outcome were
      elimination of stressors and patient's perception of effective treatment by the
      physician. CONCLUSION: This largest longitudinal study of patients with
      psychogenic tremor provides data on the clinical characteristics and natural
      history of this most common PMD. The accurate diagnosis of psychogenic tremor is
      based not only on exclusion of other causes but is also dependent on positive
      clinical criteria, the presence of which should avoid unnecessary investigation.
      The prognosis of psychogenic tremor may be improved with appropriate behavioral
      and pharmacologic management.

PMID- 16816791
TI  - Restless legs syndrome: a review.
AB  - Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an
      irresistible urge to move the limbs accompanied by uncomfortable sensations,
      leading to sleep disturbances. It is associated with psychiatric comorbidities
      and a decreased quality of life. RLS is common and most severe among females and
      the elderly. It may be primary or secondary to other conditions and may be
      familial. Linkage to several chromosomal loci have been demonstrated. The
      pathogenesis of RLS involves dopaminergic dysfunction, iron metabolism, and
      abnormalities in supraspinal inhibition. The mainstay of RLS therapy are dopamine
      agonists or levodopa. This article reviews the clinical characteristics,
      epidemiology, diagnosis, pathogenesis, and treatment of RLS.

PMID- 16816792
TI  - Lessons learned in deep brain stimulation for movement and neuropsychiatric
      disorders.
AB  - The introduction of deep brain stimulation (DBS) as a treatment for medication
      refractory essential tremor in the late 1980s revealed, for the first time, that
      "chronically" implanted brain hardware had the potential to modulate neurologic
      function with surprisingly low morbidity. Over time, the therapeutic promise of
      DBS has become evident in Parkinson's disease and dystonia. In some experienced
      centers, complex tremor disorders, such as posttraumatic Holmes tremor and the
      tremor of multiple sclerosis, are being increasingly targeted. More recently,
      other indications, including obsessive-compulsive disorder, Tourette's syndrome,
      major depression, and chronic pain, have been proposed. As the field has
      expanded, our knowledge about potential cognitive side effects of DBS has also
      expanded. This article reviews the current knowledge regarding the impact of
      stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis
      intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's
      disease, and dystonia. Also discussed are the emerging targets, what is known
      about the cognitive sequelae of DBS, and what has been learned about the
      complications and therapeutic failures.

PMID- 16816793
TI  - Non-motor aspects of Parkinson's disease.
AB  - Parkinson's disease is primarily considered to be a movement disorder and is
      defined by its motor signs. Yet, the behavioral manifestations of the disease are
      often more debilitating than its motor complications. This review will focus on
      the non-motor aspects of Parkinson's disease, including mood, psychosis,
      cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may
      occur. The phenomenology, pathology, and treatment of the behavioral symptoms of
      Parkinson's disease will be discussed.

PMID- 16816794
TI  - An overview of the Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE) study.

PMID- 16816795
TI  - Clinical trials in schizophrenia with results for the real world.
AB  - Most clinical data for antipsychotics come from studies designed to test the
      efficacy and safety of the drugs under ideal conditions, in limited subgroups of
      patients. In contrast, practical clinical trials (PCTs) are designed to test the
      effectiveness of different treatment options under conditions that more
      accurately reflect actual clinical practice. Consequently, PCTs are able to
      provide information that can be utilized by healthcare providers and other
      decision makers. Characteristics of PCTs include a clinically relevant question,
      a representative sample of patients and practice settings, sufficient power to
      identify modest relevant effects, randomization to protect against bias,
      uncertainty regarding the outcome of treatment, assessment and treatment
      protocols that enact best clinical practices, simple and relevant outcomes, and
      limited subject and investigator burden. The Clinical Antipsychotic Trials of
      Intervention Effectiveness (CATIE) research program is an example of a PCT. The
      CATIE study illustrates how PCTs, when properly designed, might be helpful in
      informing clinical decision making. Because the CATIE study was designed to
      reflect the effectiveness of antipsychotics under naturalistic clinical
      conditions, its results should have particular applicability to the arena of
      clinical practice. This article provides a discussion of the differences between
      efficacy and effectiveness studies. In assessing the practical utility of results
      from the CATIE study, much can be learned on how to shape future studies of
      effectiveness so as to better generate data that are applicable to the "real
      world."

PMID- 16816796
TI  - Interpreting the efficacy findings in the CATIE study: what clinicians should
      know.
AB  - The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)
      schizophrenia trial was an effectiveness/"pragmatic" clinical trial designed to
      compare the efficacy, tolerability, and cost-effectiveness of four atypical
      antipsychotics (olanzapine, quetiapine, risperidone and ziprasidone) and a
      conventional antipsychotic (perphenazine) for an 18-month period in patients with
      schizophrenia. The study randomized 1,460 patients with fewer exclusion criteria
      than in most trials in hopes that this would allow for a more representative
      sample of outpatients in "real world" practice. Olanzapine demonstrated
      significant superiority in time to discontinuation for all cause and for lack of
      efficacy, as well as likelihood of hospitalization for relapse; however, it was
      associated with a significantly higher rate of metabolic side effects.
      Perphenazine exhibited comparable effectiveness with quetiapine, risperidone, and
      ziprasidone, and appeared to be as well tolerated as the atypicals. However, it
      had the highest rate of drop out due to extrapyramidal symptoms and was
      restricted to patients who did not have tardive dyskinesia (TD). This article
      examines the phase 1 CATIE results to guide the clinician in understanding how to
      interpret the findings, which were intended to be a guide for clinical practice.
      The nature of the patient population, the doses of drugs relative to one another,
      inclusion of patients who were treatment resistant, and exclusion of patients
      with TD from randomization to perphenazine were potential sources of bias in the
      study. In particular, the use of a higher-than-usual peak dose of olanzapine may
      have led to the superior results achieved with it. Practical suggestions are
      given for choice of antipsychotic medication in patients with chronic
      schizophrenia.

PMID- 16816797
TI  - Implications of the CATIE trial on treatment: extrapyramidal symptoms.
AB  - Development of extrapyramidal symptoms (EPS), particularly tardive dyskinesia
      (TD), has long been a troubling side effect for patients taking antipsychotics.
      Atypical antipsychotics have been hailed as an improvement over conventional
      antipsychotics, offering similar efficacy with more favorable EPS profiles. In
      the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)
      study, which compared the conventional antipsychotic perphenazine with atypical
      antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone in patients
      with schizophrenia, no significant differences in time to treatment
      discontinuation due to intolerability were observed between treatment groups.
      However, perphenazine was associated with a higher rate of patients experiencing
      EPS as well as a significantly higher rate of discontinuation due to EPS, despite
      the fact that patients with TD at baseline were excluded from the perphenazine
      group. Unfortunately, due to short treatment duration, the CATIE study did not
      have the assay sensitivity to detect differences in TD risk among any of the
      drugs. Thus, the atypical antipsychotics remain the first line of treatment for
      most patients, with specific drug selection based on benefit-risk profiles that
      best fit the individual patient's needs. Frequent monitoring, while noting a
      patient's subjective experience, remains the best strategy for choosing therapy
      to maximize symptom relief and minimize the impact of EPS and other side effects
      over the long- term. This article explores the reported results of the CATIE
      trial regarding EPS and emphasizes the differentiation of the atypicals from
      perphenazine on EPS and how these results should be incorporated into daily
      practice for the clinician.

PMID- 16816798
TI  - Metabolic findings from the CATIE trial and their relation to tolerability.
AB  - The overall effectiveness of antipsychotics for the management of schizophrenia
      is restricted by their side-effect profiles, particularly over an extended
      treatment period. Intolerable side effects can reduce patient adherence to
      medication and often lead to treatment discontinuation. Some side effects that
      result from antipsychotic use are precursors to the metabolic syndrome, which is
      prevalent among individuals with schizophrenia and represents a significant
      source of cardiovascular risk. The Clinical Antipsychotic Trials of Intervention
      Effectiveness (CATIE) schizophrenia study assessed the efficacy of the atypical
      antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone relative to
      the conventional drug perphenazine. Additional assessments included the metabolic
      effects of these agents in patients with schizophrenia and the incidence of
      negative side effects. No significant differences were found between treatment
      groups for time to discontinuation due to intolerability, but the rates of side
      effects significantly differed (P=.04). For metabolic parameters, olanzapine was
      associated with greater and significant adverse effects on weight, lipids, and
      glucose metabolism versus the other antipsychotics tested. The CATIE results show
      that important distinctions exist among currently available atypical
      antipsychotics. Physicians should be aware of the propensity of these drugs to
      increase the risks of cardiovascular disease and diabetes in treated patients and
      tailor individual treatment decisions accordingly. This article highlights the
      metabolic findings from the CATIE schizophrenia study, and explores the
      differences shown by atypical antipsychotics, with regard to metabolic side
      effects that increase cardiovascular risk.

PMID- 16816799
TI  - Understanding the results of CATIE in the context of the field.
AB  - The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was
      undertaken to provide a valid assessment of the differences between conventional
      and atypical antipsychotics and among the atypicals themselves in patients with
      schizophrenia. The CATIE investigators reported that while none of the study
      medications were ideal, olanzapine was the most effective in terms of treatment
      discontinuation, and there were no significant differences in effectiveness
      between the conventional antipsychotic perphenazine and the atypicals quetiapine,
      risperidone, and ziprasidone. Each drug differed slightly in rates of side
      effects, with more patients discontinuing perphenazine due to extrapyramidal side
      effects and more patients discontinuing olanzapine due to weight gain and
      metabolic effects. In order for data from phase 1 of the CATIE study to be
      interpreted within the appropriate context, physicians must understand how
      aspects of study design and statistical methods affect interpretation, and how
      this trial weighs against other data in the literature. This article enumerates
      the factors that complicate our understanding of the CATIE results and compares
      these findings with those from previously published meta-analyses. It is clear
      that therapeutic and side effects of antipsychotics vary from person to person.
      The goal of schizophrenia management is to maintain pharmacotherapeutic efficacy
      and tolerability over the long-term in order to maximize treatment adherence and
      benefits. What should emerge from CATIE is a renewed commitment to tailor
      schizophrenia treatment to the individual patient for long-term management.

PMID- 16816802
TI  - For debate: did the small-bodied hominis from flores (Indonesia) suffer from a
      molecular defect in the growth hormone receptor gene (Laron syndrome)?

PMID- 16816803
TI  - Testicular anti-Mullerian hormone: history, genetics, regulation and clinical
      applications.
AB  - Anti-Mullerian hormone (AMH), also called MUllerian inhibiting substance (MIS) is
      a product of supporting gonadal Sertoli and granulosa cells. Its main
      physiological role is the induction of regression of Mullerian ducts in male
      fetuses but it also plays a role in Leydig cell steroidogenesis and in follicular
      development. It is a member of the transforming growth factor B family and
      signals through two serine/threonine kinase receptors, only one of whom, type II,
      is specific. Type I receptors and the intracytoplasmic signaling molecules are
      shared with the bone morphogenetic family. AMH is positively regulated by SF1,
      SOX9 and FSH. Testosterone is a powerful downregulator. Males lacking functional
      AMH or AMH receptor genes do not undergo regression of MUllerian derivatives
      during fetal life. AMH is an excellent marker of prepubertal testicular function
      and has gained recognition as a valuable marker of follicular reserve in adult
      women.

PMID- 16816804
TI  - Steroidogenic factor-1 (SF-1) and its relevance to pediatric endocrinology.
AB  - Steroidogenic factor-1 (SF-1) (NR5A1) is a member of the nuclear receptor
      superfamily that is expressed widely throughout the adrenal and reproductive axes
      during development and plays a central role in the function of these endocrine
      systems in post-natal and adult life. Much has been learned about the role of
      this transcription factor since its initial cloning in 1992, largely due to the
      creation of an Sf-1 (FtzF1) knockout mouse model, in vitro studies of nuclear
      receptor function and, more recently, following identification and
      characterization of patients with naturally-occurring SF-1 mutations. In this
      review, we will summarize how our knowledge of SF-1 in endocrine development and
      disease evolved to its current state, focusing on the spectrum of phenotypes
      associated with mutations in this transcription factor in patients who might
      present to a pediatric endocrinologist.

PMID- 16816805
TI  - Catch-up growth: an overview.
AB  - Normal growth in humans results from interactions between several mechanisms
      (genetic, nutritional, environmental, social and economic) that lead in concert
      to gain in weight and height. Many systemic diseases and environmental conditions
      do impair linear growth. When remission occurs, growth often resumes at a rate
      faster and beyond the normal rate for age. This phase of accelerated growth
      constitutes the "catch-up growth" phenomenon, which may be complete or incomplete
      depending upon the final height with reference preferably to the genetic target
      height. The exact mechanisms of catch-up growth remain unknown, but two
      hypotheses have been proposed: the neuroendocrine or sizostat hypothesis; and the
      growth plate hypothesis. Although no experimental data supports the former, it is
      most likely that the catch-up growth process involves both systemic and local
      (growth plate) factors, with the participation of a normally functioning GH
      Thyroid-IGF-I axis. The Ob gene protein, leptin serves as an afferent signal in a
      negative feedback loop to regulate the size of adipose tissue mass (body weight).
      Experimental studies have demonstrated its links with the GH - Thyroid - IGF-I
      and growth plate axis. To resume normal growth or initiate catch-up growth, an
      undernourished child must regain up to 85% of weight for height. This may mean
      that a close relationship exists between mechanisms regulating weight and those
      regulating linear growth. More studies are needed to determine the links that
      probably exist between the chondrocyte, adipocyte, leptin, and GH - Thyroid - IGF
      I axis on one side and the catch-up growth on the other.

PMID- 16816806
TI  - New perspectives on the pathogenesis of cerebral edema complicating diabetic
      ketoacidosis in children.
AB  - Cerebral edema is a serious complication of diabetic ketoacidosis (DKA) in
      children and is the most frequent diabetes-related cause of death in this age
      group. Many theories have been proposed to explain the pathogenesis of this
      complication, but data from the literature have not clearly supported any
      particular theory and DKA-related cerebral edema remains poorly understood. The
      question of whether DKA treatment may play a role in causing or exacerbating
      cerebral edema has been particularly controversial. Recent data have provided
      helpful evidence in favor or against various theories of pathogenesis and these
      data are the topic of the current review.

PMID- 16816807
TI  - Pseudotumor cerebri - idiopathic intracranial hypertension in the pediatric
      population.
AB  - Pseudotumor cerebri (PTC) or Idiopathic Intracranial Hypertension (IIH) is a well
      known syndrome in the pediatric population. PTC/IIH is less common in children
      than in adults, has distinct clinical manifestations and different
      characteristics in the prepubertal versus the pubertal age groups. Secondary risk
      factors are relatively common. As in adults, the pathophysiological basis of
      PTC/IIH is as yet undefined.

PMID- 16816808
TI  - Clinical utility of insulin-like growth factor-I (IGF-I) and IGF binding protein
      3 measurements in paediatric practice.
AB  - Measurements of serum insulin-like growth factor-I (IGF-I) and its major binding
      protein, IGFBP-3, are utilised in the routine clinical management of short
      children. In this review, the value of such measurements in the diagnosis of
      primary and secondary IGF-I deficiency is presented. The achievement of optimal
      growth while maintaining IGF-I within the normal range is the goal of GH
      treatment schedules used in a range of growth disorders, and thus data on IGF-I
      monitoring during initiation and maintenance phases of GH treatment are
      discussed. Comment is also made on the relationship between levels of IGF-I and
      IGFBP-3 in the population with regard to risks for cancer and cardiovascular
      disease.IGF-I and IGFBP-3 are important parameters to measure as one part of the
      process of managing short children. It is proposed that improving the clinical
      value of IGF measurement may involve measurement of specific prohormones and E
      peptides, to get closer to the pool of GH dependent IGF-I.

PMID- 16816809
TI  - Periodontal regeneration in clinical practice.
AB  - The regeneration or restitution of lost supporting tissue has always been
      considered the ideal objective of periodontal therapy. However, attempts to
      convert this intention into solid clinical practice can become tremendously
      complex, the results of which are very different from the original intention. The
      aim of this article is to offer an up-to-date, general perspective on periodontal
      regeneration, orienting the clinician within the global strategy for oral
      treatment. To this end, we revise the healing process of periodontal injury, the
      different therapeutic approaches, the interpretation of the results, and finally,
      limiting factors in periodontal regeneration.

PMID- 16816810
TI  - Structural and functional salivary disorders in type 2 diabetic patients.
AB  - Diabetes mellitus type 2 is the most common metabolic disorder and it causes an
      important morbimortality. The structural modifications in the parotid gland
      (sialosis) had already been described in these patients and could result in
      variations in the salivary composition, as well as an increase in periodontal and
      dental pathology. OBJECTIVES: To compare the biochemical findings in the saliva
      and to correlate these biochemical disturbances with the morphologic findings
      previously described. PATIENTS AND METHODS: Clinical information were gathered
      about 33 patients, 17 had type 2 diabetes. Samples of whole saliva were obtained
      for biochemical analysis and serum samples to determine metabolic control.
      RESULTS: In the diabetics saliva we found urea and total proteins increased and
      reduced levels of microalbumina. Salivary glucose was only augmented in patients
      with poor metabolic control. Clinical symptoms of xerostomia were present in
      76,4% and dental and periodontal disease in 100%. The parotid gland was
      characterised by the presence of small acini, lipid intracytoplasmic droplets, as
      well as adipose stroma infiltration. The acinar cytoqueratins expression was
      heterogeneous and very positive in the hyperplasic ducts. CONCLUSIONS: These
      biochemical disorders in the saliva of the type 2 diabetic patients would be
      related with the structural changes previously observed in parotid glands.

PMID- 16816811
TI  - Stafne bone cavity--magnetic resonance imaging.
AB  - A case of Stafne bone cavity (SBC) affecting the body of the mandible of a 51
      year-old female is reported. The imaging modalities included panoramic
      radiograph, computed tomography (CT) and magnetic resonance (MR) imaging.
      Panoramic radiograph and CT were able to determine the outline of the cavity and
      its three dimensional shape, but failed to precisely diagnose the soft tissue
      content of the cavity. MR imaging demonstrated that the bony cavity is filled
      with soft tissue that is continuous and identical in signal with that of the
      submandibular salivary gland. Based on the MR imaging a diagnosis of SBC was made
      and no further studies or surgical treatment were initiated. MR imaging should be
      considered the diagnostic technique in cases where SBC is suspected. Recognition
      of the lesion should preclude any further treatment or surgical exploration.

PMID- 16816812
TI  - Delayed contact sensitivity on the lips and oral mucosa due to propolis-case
      report.
AB  - We report a rare case of a patient who was referred to the Department of Oral
      medicine in Zagreb, Croatia. The patient was 20 years old, otherwise healthy and
      not taking any medication. She presented with irregular erosions partially
      covered with pseudomembranes that involved both lips and retrocomissural mucosa.
      Discrete erosion was also noticed on her lower lingual gingiva in the area 42.
      She reported a propolis solution self-medication for treatment of recurrent
      aphthous ulcers. After ten days of propolis application, lip and oral lesions
      developed. Patch test to propolis was proven. We highlight the fact that some
      folk medicine medications, such as propolis, although being known for many
      decades to be helpful in various conditions, in some individuals might lead to
      unwanted side-effects due to its antigenic potential. Additionally, every
      colleague, during the differential diagnosis of the oral lesions must bear in
      mind unwanted reactions to folk medicine products.

PMID- 16816813
TI  - Follicular adenomatoid odontogenic tumor: immunohistochemical study.
AB  - Adenomatoid odontogenic tumor (AOT) is an uncommon benign odontogenic lesion that
      affects young patients, with female predominance, mainly in second decade,
      showing a radiolucent unilocular image associated with an unerupted tooth,
      usually a canine. In spite of previous and confusing denominations, such as
      adenoameloblastoma or adenomatoid ameloblastic tumor, AOT is a benign tumor with
      a very low rate of recurrence, that show a peculiar morphological picture
      (basaloid appearance with glandular-like structures, calcifying areas, and
      amiloid-like material) that allow its histopathological recognition. We present a
      clinicopathological analysis of a case of follicular AOT affecting the mandible
      in a 9 years-old female patient associated with unerupted lower left canine.
      Immunohistochemical study showed some data previously unrecognised. All cellular
      types that composed AOT showed nuclear positivity for p63 indicating a basal
      characterization in the different cellular components. According to its benign
      character and low potential for recurrence, AOT revealed a scant proliferative
      activity (2-3% nuclei showed Ki-67 positivity) limited to some epithelial nodules
      (AE1-3 +) of fusiform appearance. Absence of reactivity for hormonal receptors
      (RE and RPg) excluded a possible hormonodependence in AOT that could explain the
      observed female predominance.

PMID- 16816814
TI  - Immunohistochemical evaluation of metallothionein in palatal mucosal cells of
      mice treated with 4NQO.
AB  - OBJECTIVE: Metallothionein (MT) may play a preventive role in various
      carcinogenic process. 4NQO is an alkaline compound and potent mutagen that causes
      the formation of DNA adducts. The purpose of this study was to evaluate the
      immunoexpression of MT in palatal cells of mice submitted to the carcinogen 4NQO.
      STUDY DESIGN: C57BL/6 mice received applications of 4NQO to palate for periods of
      8, 16, 20 and 24 weeks (experimental group). A control group received only
      applications of propylene glycol for the same periods. Subsequently animals of
      experimental and control groups were sacrificed and the palate was histologically
      analysed and MT immunohistochemistry performed. RESULTS: Although morphological
      atypical features were scant, the expression of MT was higher in the experimental
      group in comparison to controls. There was an amplified induction of MT
      expression in oral epithelium of mice treated by 4NQO. CONCLUSION: These results
      suggest that MT may act as an endogenous defensive factor against 4NQO in early
      phases of oral carcinogenesis.

PMID- 16816815
TI  - Multiple oral fibropapillomatosis as an initial manifestation of Cowden Syndrome.
      Case report.
AB  - Cowden syndrome is a rare hereditary disease included within hamartoma-type
      gastrointestinal polyposis. It is characterised by associated mucocutaneous
      anomalies and by the extraordinary tendency to develop malignant neoplasia,
      mainly in the breast and thyroid. Early diagnosis of the syndrome and adequate
      tumoral screening in patients with mucocutaneous papillomatosis make it possible
      to make an earlier diagnosis of associated pathologies which have great morbidity
      when detected late. We present the case of a patient diagnosed with Cowden
      syndrome after consultation for labial papillomatous lesions of long evolution
      who was subsequently treated for breast and kidney cancer in initial stages. The
      correct diagnosis of a banal pathology of oral mucosa made it possible for us to
      take early action against the neoplastic pathology associated with this disease.

PMID- 16816816
TI  - Helicobacter pylori in the dental plaque: is it of diagnostic value for gastric
      infection?
AB  - AIM: The aim of present study was the assessment of association of helicobacter
      pylori of dental plaque and stomach in a more homogenous population and also to
      determine the diagnostic value of dental plaque for gastric infection. MATERIALS
      AND METHODS: Based on the results of Rapid urease test (RUT) on specimens from
      gastric antrum, 88 patients with symptoms of dyspepsia were assigned into two
      groups of infected and non-infected with helicobacter pylori. Supragingival
      plaque samples were collected from mandibular first and second molar area using
      and sterile curette and were investigated using RUT. Statistical analysis of data
      was performed using chi-square test and independent t-test. RESULTS: H. pylori
      was detected in 34.1 % of dental plaque specimens. The prevalence of helicobacter
      pylori infection in dental was 31.8 % and 36.4 % in patients with and without
      gastric infection (P=0.6). Also the interaction of age and infection was not
      significant but the prevalence of H. pylori both in the dental plaque and the
      stomach of male patients was higher than female patients. CONCLUSION: There is
      not any significant association between the helicobacter pylori of the dental
      plaque and the stomach. Also the dental plaque can not be used as a primary
      diagnostic aid for gastric infection.

PMID- 16816817
TI  - Hamular Bursitis and its possible craniofacial referred symptomatology: two case
      reports.
AB  - The diagnosis of craniofacial pain is conditioned by the interdisciplinary
      management of its presentation especially in the absence of unique and objective
      signs. Bursitis is a pathological entity recently found in the hamular area and
      should be included in the diagnosis for exclusion of temporomandibular disorders
      (TMD), ear-nose-throat pathologies, due to the similar symptomatology to other
      head and neck conditions. The hamular process bursitis is a painful condition
      that can easily be confused with glosopharinge or trigeminal neuralgia that
      generates an uncomfortable feeling in the oropharinge with ipsilateral referred-
      heteretopic-symptomatology to the head. This pathology, in chronic states, can be
      responsible for the amplification of the pain perceived by the central excitation
      effect. In this report are presented two clinical cases of hamular bursitis and
      its conservative therapeutic management. The recognition of the inflammation of
      the bursa of the tensor veli palati muscle supplies the specialist with another
      tool in the management of craniofacial pain.

PMID- 16816818
TI  - Incidence of oral sinus communications in 389 upper thirmolar extraction.
AB  - INTRODUCTION: The incidence of oral sinus communications (OSC) following the
      extraction of an upper third molar remains uncertain. OBJECTIVES: The purpose of
      this study was to determine the incidence of OSC following the extraction of 389
      consecutive upper third molars during 2003 in the Master of Oral Surgery and
      Orofacial Implantology (Barcelona University, Spain). PATIENTS AND METHOD:
      Different variables were recorded, including patient age, sex, molar angulation,
      surgical technique and radiological sinus proximity, to determine the relation
      between third molar extraction and the incidence of OSC. RESULTS: Only 5.1% (95%
      CI: 2.2-7.3%) of the upper molar surgical extractions produced OSC, the risk of
      which was found to be similar in all age groups and increased with the depth of
      third molar inclusion, the complexity of the surgical technique and the
      performance of an ostectomy.

PMID- 16816819
TI  - Retrospective study of 145 supernumerary teeth.
AB  - OBJECTIVE: The goal of the present retrospective study is to describe the
      distribution of the supernumerary teeth in a population of patients that have
      been attended at the Public Clinic of the Department of Oral Surgery. BACKGROUND:
      Supernumerary teeth and multiple hyperdontia are usually associated with
      different syndromes, such as Gardner syndrome, or with facial fissures; however,
      they can appear in patients without any pathology. Their prevalence oscillates to
      0.5-3.8% in patients with permanent teeth and to 0.35-0.6% in patients with
      primary teeth. PATIENTS AND METHODS: A total of 36,057 clinical histories of
      patients that were admitted at the clinic between September of 1991 and March of
      2003 were revised. The following data were extrapolated: age, sex, number of
      extracted supernumerary teeth, localization, morphology and type of supernumerary
      teeth. Consequently, 102 patients were included into the present study. RESULTS:
      Of the 147 supernumerary teeth identified in the oral cavities of patients 145
      were extracted. The most frequent supernumerary teeth identified were mesiodens
      (46.9%), followed by premolars (24.1%) and fourth molars or distal molars (18%).
      As for location, 74.5% of the supernumerary teeth were found in the superior
      maxillary bone and 46.9% of the supernumerary teeth were present in the
      palatine/lingual area. Heteromorphology was found in two thirds of the
      supernumerary teeth, with conical shape being the most frequent. Finally, 29.7%
      of the supernumerary teeth had occlusion with permanent teeth, and mesiodens were
      the predominating type of supernumerary teeth that showed this feature.
      CONCLUSIONS: Mesiodens very frequently cause retention of permanent incisors,
      which erupt spontaneously after the extraction of supernumerary teeth, if there
      is sufficient space in the dental arch and if they conserve the eruptive force.
      Generally, supernumerary premolars are eumorphic and are casually discovered
      during radiological exam, if not producing any symptomology.

PMID- 16816820
TI  - A review of facial injuries due to dog bites.
AB  - Bite injuries to the head and neck region can result in facial disfigurement with
      distressing physical and psychological consequences. This article reviewed the
      causes and management of facial bite wounds due to dog bites. A PUBMED search of
      the National Library of Medicine from 1995 to December 2005 was conducted.
      Keywords used in the search were facial wound, bite wound, dog bite. The results
      showed that the risk factors for dog attacks include: school-aged children, male,
      households with dogs, male dogs and certain breeds (german shepherds, bull
      terriers, blue/red heelers, dobermans and rottwellers). Early management of such
      complex injuries usually guarantees satisfactory outcome. Most of the cases
      involve a known dog (friends, neighbors) and family pet. Although animal bites
      are not the most accounted children injuries, deaths may a result of these
      attacks. Antibiotic therapy is indicated for infected bite wounds and fresh
      wounds considered at risk for infection, such as extremely large wounds, large
      hematoma, and cat bites, that appear be more infected than dog bites. Tetanus
      immunization status and the risk of rabies infection should be routinely
      addressed in bite wound management. Prevention strategies should be considered
      for preventing dog bites.

PMID- 16816821
TI  - Pyogenic granuloma.

PMID- 16816822
TI  - Antibiotic prophylaxis in pediatric odontology. An update.
AB  - Most orofacial infections are of odontogenic origin, and are of a self-limiting
      nature, characterized by spontaneous drainage. The causal bacteria are generally
      saprophytes. On the other hand, invasive dental interventions give rise to
      transient bacteremia. When an oral lesion is contaminated by extrinsic bacteria,
      the required antibiotic treatment should be provided as soon as possible. In the
      case of pulpitis, such treatment is usually not indicated if the infection only
      reaches the pulp tissue or the immediately adjacent tissues. In the event of
      dental avulsion, local antibiotic application is advised, in addition to the
      provision of systemic antibiotics. The dental professional must know the severity
      of the infection and the general condition of the child in order to decide
      referral to a medical center. Prophylaxis is required in all immunocompromised
      patients, as well as in individuals with cardiac problems associated with
      endocarditis, vascular catheters or prostheses. Penicillin V associated to
      clavulanic acid and administered via the oral route is known to be effective
      against odontogenic infections. In the case of allergies to penicillin, an
      alternative drug is clindamycin. Most acute infections are resolved within 3-7
      days. In recent years, the tendency is to reduce general antibiotic use for
      preventive or therapeutic purposes.

PMID- 16816823
TI  - Telescopic crowns in adult case with lip and palate cleft. Update on the etiology
      and management.
AB  - Lip and palatal clefts are among the most important congenital craniofacial
      malformations to be taken into account in general dental practice, due to their
      high incidence and important repercussions upon the oral cavity. The underlying
      causes are genetic and fundamentally environmental, and the disorders manifest as
      early as in the embryonic period. Males are predominantly affected, with a 7:3
      ratio versus females. Our patient, a 20-year-old male, presented the most common
      association, i.e., total unilateral hare lip with palatal cleft. A description is
      provided of the treatment for his dental problem, together with an update on the
      etiology and management of adults with malformations of this kind.

PMID- 16816824
TI  - Chromatic appreciation in the clinic and the laboratory.
AB  - Aesthetic requirement in dentistry is getting more and more important every day.
      One of its basic principles is the correct selection of colour for the
      restorations. Colour is a quality which is modulated by a series of factors,
      environmental and individual, that the clinic must know. Colour measurement by
      the human eye can induce to an appreciation mistake if it doesn't follow a
      correct protocol of light conditions and observation technique, checked by the
      authors, simplifying it with a practical focusing. Colour measurement instruments
      have appeared recently, trying to correct the problems of conventional technique.

PMID- 16816825
TI  - Oral health survey of the child population in the Valencia Region of Spain
      (2004).
AB  - INTRODUCTION (BASIS AND OBJECTIVES): The objectives of this study were to study
      the evolution of child oral health in the Valencia Region and establish a six
      year interval for these surveys, at a time of major demographic changes
      associated with immigration into the region. MATERIALS AND METHODS: A cross
      sectional study was conducted in a random sample of 509 children aged 6 years,
      478 aged 12 years and 401 aged 15-16 years. The clinical examinations were
      performed by calibrated dentists (Kappa > 0.85). RESULTS: Caries prevalence was
      32% at 6 years of age (dft=1.08) in primary dentition and 42.5% at 12 years
      (DMFT=1.07) and 55.9% at 15-16 years (DMFT=1.84) in permanent dentition. Caries
      levels in immigrant children were significantly high. The mean numbers of
      sextants with bleeding were 0.16, 1.58 and 1.10 while the scores for sextants
      with calculus were 0.15, 0.76 and 0.88, respectively. CONCLUSIONS: Caries levels
      in both primary and permanent dentition have remained stable at 6 and 12 years of
      age and have continued to fall in the 15-16-year-old age group. Immigrant
      children have high caries levels and are a population group in serious need of
      treatment and prevention plans.

PMID- 16816826
TI  - Two routes of hormonal replacement therapy in symptomatic menopausal women after
      kidney transplantation.
AB  - OBJECTIVES: The assessment of efficacy and safety of two regimens of hormonal
      replacement therapy (HRT) in women after kidney transplantation with climacteric
      symptoms. MATERIAL AND METHODS: Combined transdermal or transdermal-oral hormonal
      replacement therapy was administered to 86 kidney-transplanted women, aged 31-52
      years, with moderate to severe climacteric symptoms in years 1995-2005. The
      patients underwent follow-up examinations one, three and six months after onset
      of the therapy and every four months subsequently. Blood pressure, body weight,
      sex hormone profile, serum parameters of both kidney and liver function,
      endometrial image in transvaginal sonography and reduction of climacteric
      symptoms were assessed. RESULTS: The mean time of the therapy was 5.6 years for
      transdermal-oral regimen (54 patients) and 4.7 years for transdermal regimen (32
      patients). Most patients reported reduction of climacteric symptoms and improved
      life quality after 6 months of HRT. 28% of women discontinued therapy for medical
      indications, most often due to significant deterioration of liver function. One
      case of profound vein thrombosis was noted. 21% of women decided to discontinue
      therapy after the results of the WHI trial had been published. CONCLUSIONS:
      Hormonal replacement therapy is effective in climacteric symptoms relief and
      improvement of life quality in kidney transplanted women. Higher rate of side
      effects observed in that group of patients contributes to the need for frequent,
      attentive surveillance. Further studies should be conducted to establish the
      optimal doses and routes of administration of HRT as well as to assess the range
      of necessary follow-up examinations.

PMID- 16816827
TI  - The role of CpG islands hypomethylation and abnormal expression of neuronal
      protein synuclein-gamma (SNCG) in ovarian cancer.
AB  - BACKGROUND: The synucleins are a family of small cytoplasmic proteins that are
      expressed predominantly in neurons. Recently, their expression has been found
      also in many human cancers. AIM: To understand the molecular mechanisms
      underlying the abnormal expression of SNCG in malignant ovarian tumors, in this
      study, we examined the methylation status of a CpG island located in exon 1 of
      SNCG gene in a panel of ovarian malignant tumors to determine if DNA methylation
      is related to clinical and histological tumor characteristics. METHODS: SNCG mRNA
      expression in tumor samples was assessed by RT-PCR. Methylation status of SNCG
      gene was studied using methylation specific PCR (MSP). RESULTS: Study group
      included 43 ovarian carcinoma samples (40 primary and 3 metastatic). The
      expression of SNCG mRNA was detectable in 33 of 43 ovarian cancer cases (76.7%).
      There were no significant differences in the mRNA expression between serous or
      nonserous tumors. The presence of SNCG mRNA in tumor samples was not correlated
      with age and menopausal status of patients, also no correlation was found with
      clinical stage or histological grading of malignant tumors. In 29 of 43 (67.4%)
      cases of tumors unmethylated product of MSP amplification was present. In a group
      of SNCG mRNA-positive tumors there were 75.7% (25 of 33) cases with demethylated
      or hypomethylated exon 1 of SNCG. The differences between the groups were
      statistically significant (chi2 =4.46; p=0.034). Demethylation of SNCG was not
      related to clinical tumor stage (p>0.05), but it was strongly associated with
      tumor grading (chi2=6.66; p=0.035). Aberrant methylation of SNCG was more often
      seen in tumors of women after menopause (78.2% vs 55%). In postmenopausal women
      18 of 33 (62.1%) tumor samples synuclein-gamma mRNA expression was found, however
      the differences were not statistically significant. No correlations between SNCG
      hypomethylation and patient age, clinical stage and tumor grading were found. In
      9 of 43 samples (21%) both products of amplification with methylated or
      unmethylated primer sets were found. In all of these cases SNCG mRNA was present.
      CONCLUSIONS: SNCG mRNA is expressed in a substantial proportion of malignant
      ovarian tumors and demethylation is an important event in abnormal synuclein
      gamma expression in most of these cases.

PMID- 16816828
TI  - The influence of scopolamine and extreme temperatures on the lipid level in some
      mouse organs.
AB  - OBJECTIVES: The effect of scopolamine administration at dose 0,5 g/kg b.w. and
      high (+40 degrees C) and low (+4 degrees C) temperature on the level of
      triacyloglycerides, total lipids and cholesterol in the mouse liver, kidney and
      muscle of males and females. METHODS: The homogenates of the liver, kidney and
      muscle were taken for examination. The concentrations of triacyloglycerides,
      total lipids and cholesterol was estimated according to the Bio-La-Tests
      (Poland). RESULTS: The concentration of triacyloglycerides and total lipids in
      the liver, kidney and muscle increased of males and females after scopolamine
      injections and after exposure to high and low temperatures. CONCLUSION:
      Scopolamine may effect an increase in the rate of the lipid metabolism.

PMID- 16816829
TI  - The effect of repetitive transcranial magnetic stimulation (rTMS) on symptoms in
      obsessive compulsive disorder. A randomized, double blind, sham controlled study.
AB  - BACKGROUND: The goal of our study is to assess whether transcranial magnetic
      stimulation (rTMS) would facilitate the effect of antidepressant in OCD patients.
      METHOD: The aim of the randomized, double-blind, sham controlled study was to
      compare the 2 and 4 week efficacy of the 10 sessions rTMS with sham rTMS in
      serotonin reuptake inhibitor resistant OCD patient. Thirty three right-handed
      patients were randomly assigned to either active rTMS or to sham rTMS. Active
      rTMS with the frequency of 1 Hz at 110% of motor threshold (MT) was administered
      over the left dorso-lateral prefrontal cortex. The same time schedule was used
      for sham administration. Thirty patients finished the study, three patients'
      dropped out at the beginning. Psychopathology was assessed by CGI, HAMA, Y-BOCS
      and BAI before the treatment, immediately after the experimental treatment, and 2
      weeks after the experimental treatment by an independent reviewer. RESULTS: Both
      groups improved during the study period but the treatment effect did not differ
      between them in any of the instruments. CONCLUSION: Low frequency rTMS
      administered over the left dorso-lateral prefrontal cortex during 10 daily
      sessions did not differ from sham rTMS in facilitating the effect of serotonin
      reuptake inhibitors in OCD patients.

PMID- 16816830
TI  - The effect of melatonin on glutathione and glutathione transferase and
      glutathione peroxidase activities in the mouse liver and kidney in vivo.
AB  - OBJECTIVES: The changes in reduced glutathione (GSH), activity of glutathione
      transferase (GST) and glutathione peroxidase (GSPx) after administration of
      exogenous melatonin (N-acetyl-5-methoxy-tryptamine) at a dose 20 mg/kg b.w. were
      investigated for five and ten days in the liver and kidney of male and female
      mice. METHODS: The liver and kidney were homogenized in 0.1 M phosphate buffer.
      Glutathione level and activity of studied glutathione enzymes were determined in
      the supernatants. RESULTS: Melatonin caused an increase in glutathione level, the
      activity of glutathione peroxidase as well as glutathione transferase in the
      examined organs. CONCLUSION: Melatonin may exert some effects on the activity of
      enzymes engaged in the metabolism of thiol compounds in the cell. Glutathione may
      be useful for monitoring melatonin's protective role on cell damage.

PMID- 16816831
TI  - Substance P plasma concentration during the LH preovulatory surge of the
      menstrual cycle in the human.
AB  - OBJECTIVES: In order to determine the exact pattern of plasma Substance P (SP)
      concentration during the LH preovulatory surge and the functional correlates
      which could exist between plasma SP, LH, 17 beta-estradiol (E2) and Progesterone,
      we performed a detailed analysis of changes in plasma SP concentration, during
      the critical phases of the LH preovulatory surge in the Human. METHODS: The
      experimental study was performed in 21 women between the ages of 26 and 35 years.
      For each subject, blood samples were taken every 15 min, between 07:00 a.m. and
      09:00 a.m. for 3 consecutive days when E2 plasma values reached at last 125
      pg/ml. Then, each subject, according to the mean LH value of each day, was
      classified into one of the following groups: 1) the day before the day of the
      ascending phase, 2) the day of the ascending phase, 3) The day of the LH surge,
      4) the day of the descending phase, 5) the day after the day of the descending
      phase. RESULTS: Mean SP plasma values for the day of the LH peak, the day of the
      descending phase and the day after the day of the descending phase were all
      significantly higher than the values of the day of the ascending phase. Overall,
      there was an almost linear increase for plasma SP values between the day before
      the day of the ascending phase and the day after the day of the descending phase
      Also,this linear increase in plasma SP concentration exhibited a positive
      correlation (p = 0.016) with plasma progesterone concentrations which also
      started to increase on the day of the ascending phase of the LH surge.
      CONCLUSIONS: Taken together with previous results which have shown that the
      administration of a SP antagonist reduces both the amplitude and the duration of
      the preovulatory LH surge in the monkey, the increase in plasma SP
      concentrations, possibly driven by the rise in serum progesterone concentration,
      which take place at the time of the preovulatory LH surge, is certainly an
      important element of the Hypothalamo-Pituitary-Gonadal interactive network
      necessary for the full development of the preovulatory LH surge in the Human.

PMID- 16816832
TI  - Reductions in plasma prolactin during acute erythropoietin administration.
AB  - OBJECTIVES: The presence of erythropoietin (EPO) and its receptors in several
      central nervous system regions indicates additional functions beside its
      hematopoietic role. Preclinical data suggest that it may slow down the process of
      neuronal loss, and that EPO may cause dopamine release, and thus influence
      hormone release, especially prolactin. This possibility has not yet been studied
      in humans. METHODS: During a clinical trial on possible protective effects in
      patients with amyotrophic lateral sclerosis (ALS), we studied the acute effects
      of EPO administration on prolactin, the release of which is under tonic
      inhibition of hypothalamic-pituitary dopaminergic activity. Prolactin as well as
      EPO levels were estimated in blood samples taken every 30 min over 2 hours after
      administration of 3000 IU EPO i.v. in seven male and four female patients with
      ALS. RESULTS: The baseline PRL levels of the 11 patients were all within normal
      range (4.5-10.5 ng/ml). EPO administration caused a significant reduction in
      prolactin levels, maximal at 60 min after administration. Reductions in PRL were
      not related to EPO dose (IU per kg body weight), or to duration of illness.
      CONCLUSIONS: The findings indicate that EPO promotes dopamine release in humans,
      and is consistent with preclinical data showing that EPO releases dopamine from
      rat striatal slices. Previous reports showed that dopaminergic neurons express
      EPO receptors, which exert a facilitating action on dopamine release, and the
      present data indicate that this may hold true in humans.

PMID- 16816833
TI  - Improved circadian sleep-wake cycle in infants fed a day/night dissociated
      formula milk.
AB  - On the basis of the circadian nutritional variations present in breast milk, and
      of the implications for the sleep/wake cycle of the nutrients present in infant
      formula milks, we designed a formula milk nutritionally dissociated into a
      Day/Night composition. The goal was to improve the bottle-fed infant's sleep/wake
      circadian rhythm. A total of 21 infants aged 4-20 weeks with sleeping
      difficulties were enrolled in the three-week duration study. The sleep analysis
      was performed using an actimeter (Actiwatch) placed on an ankle of each infant to
      uninterruptedly record movements during the three weeks. The dissociated Day
      milk, designed to be administered from 06:00 to 18:00, contained low levels of
      tryptophan (1.5g/100g protein) and carbohydrates, high levels of proteins, and
      the nucleotides Cytidine 5 monophosphate, Guanosine 5 monophosphate and Inosine 5
      monophosphate. The dissociated Night milk, designed to be administered from 18.00
      to 06.00, contained high levels of tryptophan (3.4g/100g protein) and
      carbohydrates, low levels of protein, and the nucleotides Adenosine 5
      monophosphate and Uridine 5 monophosphate. Three different milk-feeding
      experiments were performed in a double-blind procedure covering three weeks. In
      week 1 (control), the infants received both by day and by night a standard
      formula milk; in week 2 (inverse control), they received the dissociated milk
      inversely (Night/Day instead of Day/Night); and in week 3, they received the
      Day/Night dissociated formula concordant with the formula design. When the
      infants were receiving the Day/Night dissociated milk in concordance with their
      environment, they showed improvement in all the nocturnal sleep parameters
      analyzed: total hours of sleep, sleep efficiency, minutes of nocturnal
      immobility, nocturnal awakenings, and sleep latency. In conclusion, the use of a
      chronobiologically adjusted infant formula milk seems to be effective in
      improving the consolidation of the circadian sleep/wake cycle in bottle-fed
      infants.

PMID- 16816834
TI  - Growth-inhibitory action of melatonin and thiazolidinedione derivative CGP 52608
      on murine 16/C breast cancer cells.
AB  - OBJECTIVES: Melatonin may influence directly tumor cells through the specific
      binding sites. The best known melatonin binding sites are membrane receptors.
      Recently, the participation of nuclear signalling via estrogen as well as RZR/ROR
      receptors in oncostatic action of melatonin on the breast cancer has been widely
      discussed. The aim of present study was to investigate effects of melatonin, the
      selective ligand for nuclear RZR/ROR receptors - CGP 52608, and methotrexate on
      growth of murine 16/C breast cancer cells. MATERIAL AND METHODS: The experiment
      was performed in vitro. The breast cancer cells were incubated for 2 days in the
      presence of melatonin, CGP 52608 (at concentrations of 10(-5)M, 10(-7)M, 10(-9)M,
      10-(11)M ) and methotrexate (at concentrations of 0.25 and 0.125 microg/ml). The
      growth of cells was measured using the modified Mossman method. RESULTS: All
      examined compounds significantly inhibited the growth of cancer cells. The
      effects of MLT and CGP 52 608 were comparable with suppression caused by
      methotrexate. The significant differences of efficacy between two examined
      concentrations of methotrexate were not observed. CONCLUSION: The obtained data
      together with our previous results indicate that nuclear receptors RZR/ROR play
      an important, although not sufficiently recognized role in the oncostatic action
      of melatonin.

PMID- 16816835
TI  - Endothelin ETA and ETB receptor expression in the human trigeminal ganglion.
AB  - OBJECTIVES: Endothelin is a potent peptide mediator that is synthesized by a
      number of cells. Previous studies have revealed the occurrence of endothelin in
      nerve cell bodies of some peripheral ganglia. Endothelin mediates its effects via
      two distinct receptor subtypes ETA and ETB. The present study was designed to
      investigate the presence of these two receptors in the human trigeminal ganglion.
      METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to
      show the presence of mRNA encoding ETA and ETB receptors in the human trigeminal
      ganglion. To localize the protein immunocytochemistry with antibodies against the
      endothelin receptors was used. RESULTS: Reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis revealed mRNA for both receptor subtypes in the human
      trigeminal ganglion. Immunocytochemistry revealed numerous cell bodies containing
      the ETA and the ETB receptor proteins. CONCLUSIONS: The expression of ETA and ETB
      receptors in the human trigeminal ganglion suggests a role for endothelin in
      autonomic and sensory neural transmission.

PMID- 16816836
TI  - Distribution of antidepressants between plasma and red blood cells.
AB  - OBJECTIVE: The distribution of different antidepressants between plasma and red
      blood cells (RBCs) or between water and erythrocyte membranes (ghosts) has not
      been sufficiently compared so far. MATERIALS AND METHODS: Distribution of seven
      antidepressants (amitriptyline, nortriptyline, imipramine, desipramine,
      didesmethylimipramine, dothiepin, and citalopram) was measured in vitro in small
      volumes of blood or erythrocyte membrane suspension using radiolabeled drugs.
      Blood samples were taken from healthy subjects. RESULTS: The distribution of
      antidepressants between plasma and RBCs is strongly affected by temperature;
      however, it does not depend on the antidepressant concentration in the range of
      their therapeutic concentrations. The data analysis proved that the ratio of RBCs
      to plasma volume concentrations is the suitable parameter characterizing
      antidepressant distribution in whole blood. Significantly higher ratios of RBCs
      to plasma concentrations were found for demethylated metabolites of tricyclic
      antidepressants and in the case of citalopram. Citalopram showed the highest
      accumulation in intact RBCs and at the same time the lowest binding to isolated
      membranes. The binding of drugs to isolated erythrocyte membranes was much higher
      than in whole blood. CONCLUSION: The concentration ratio of antidepressant in
      RBCs and in plasma is sensitive not only to the binding properties of plasma
      proteins and cell membranes, but also to changes in drug molecule, both in
      aminopropyl chain and in aromatic rings. This ratio is to a large extent
      characteristic of a particular antidepressant.

PMID- 16816837
TI  - Current status and future prospects of needle-free liquid jet injectors.
AB  - Needle-free liquid jet injectors have been used for more than 50 years for
      parenteral delivery of vaccines and drugs. Although excellent bioavailability has
      been reported for a number of drugs, occasional pain and bruising have limited
      wide acceptance of jet injectors. This article reviews jet injectors with respect
      to their current clinical applications, emerging applications, mechanistic
      understanding and future prospects.

PMID- 16816838
TI  - B cells move to centre stage: novel opportunities for autoimmune disease
      treatment.
AB  - The B-cell arm of the immune system has long been appreciated for its crucial
      role in pathogen resistance, but in the study of many autoimmune diseases, T
      cells have dominated the limelight for decades. However, the development of the B
      cell-depleting antibody rituximab as a lymphoma therapy has provided a tool to
      probe the contribution made by B cells in several immune disorders. Recently, the
      success of B-cell depletion with rituximab in the treatment of rheumatoid
      arthritis has stimulated investigation of its effects in several other immune
      disorders, and considerable interest in the potential of drugs that can modulate
      B-cell function for the treatment of such diseases in general. This article
      discusses the role of B cells in a range of autoimmune disorders, including
      rheumatoid arthritis and systemic lupus erythematosus, and analyses approaches to
      therapeutic B-cell manipulation.

PMID- 16816839
TI  - Applications of ESI-MS in drug discovery: interrogation of noncovalent complexes.
AB  - For many years, analytical mass spectrometry has had numerous supporting roles in
      the drug development process, including the assessment of compound purity;
      quantitation of absorption, distribution, metabolism and excretion; and compound
      specific pharmacokinetic analyses. More recently, mass spectrometry has emerged
      as an effective technique for identifying lead compounds on the basis of the
      characterization of noncovalent ligand-macromolecular target interactions. This
      approach offers several attractive properties for screening applications in drug
      discovery compared with other strategies, including the small quantities of
      target and ligands required, and the capacity to study ligands or targets without
      having to label them. Here, we review the application of electrospray ionization
      mass spectrometry to the interrogation of noncovalent complexes, highlighting
      examples from drug discovery efforts aimed at a range of target classes.

PMID- 16816840
TI  - Drug discovery in the ubiquitin-proteasome system.
AB  - Regulated protein turnover via the ubiquitin-proteasome system (UPS) underlies a
      wide variety of signalling pathways, from cell-cycle control and transcription to
      development. Recent evidence that pharmacological inhibition of the proteasome
      can be efficacious in the treatment of human cancers has set the stage for
      attempts to selectively inhibit the activities of disease-specific components of
      the UPS. Here, we review recent advances linking UPS components with specific
      human diseases, most prominently cancer and neurodegenerative disorders, and
      emphasize potential sites of therapeutic intervention along the regulated protein
      degradation pathway.

PMID- 16816841
TI  - Minimally Invasive Limited Ligation Endoluminal-assisted Revision (MILLER) for
      treatment of dialysis access-associated steal syndrome.
AB  - Dialysis-associated steal syndrome (DASS) is defined as a clinical condition
      caused by arterial insufficiency distal to the dialysis access owing to diversion
      of blood into the fistula or graft. The incidence of symptomatic DASS requiring
      treatment is 1-8%. The etiology is iatrogenic and symptoms are quite
      debilitating. Banding of the access inflow has largely been abandoned because of
      the inherent problem with balancing fistula flow with distal flow complicated by
      a high incidence of subsequent access thrombosis. In this study, we are reporting
      a modification to the traditional banding procedure, which markedly improves
      banding outcomes. We are reporting 16 patients who underwent a new standardized
      minimally invasive banding procedure performed in an outpatient setting with
      minimal morbidity. This modified banding procedure requires a small (1-2 cm) skin
      incision for the placement of a ligature and utilizes a 4 or 5 mm diameter
      endoluminal balloon to achieve and standardize the desired reduction of inflow
      size. All 16 patients had immediate symptomatic and angiographic improvement
      after the procedure. Follow-up showed none of the patients had recurrence of
      symptoms or thrombosis of the access. In our experience, this procedure is an
      excellent treatment option because of its simplicity and should be considered as
      a first-line treatment for patients with DASS.

PMID- 16816842
TI  - Polycystic kidney disease: cell division without a c(l)ue?
AB  - Polycystic kidneys are caused by an amazingly broad array of genetic mutations
      and manipulations. The ciliary hypothesis has evolved as the unifying concept of
      cystogenesis: cilia, bend by fluid flow, initiate a calcium influx that prevents
      cyst formation. The integrity of ciliary functions has been linked to the
      polycystic kidney disease gene products localizing to the cilium or the basal
      body/centrosome. Until recently, the signals and cellular programs located
      downstream of the ciliary-mediated calcium flux have remained elusive. Now,
      several reports point towards a role of the cilium or the basal body/centrosome
      complex in planar cell polarity, a pathway that orients cell in the plane of a
      tissue layer. First, Inversin, a protein mutated in nephronophthisis type II was
      found to act as a switch between the canonical and the noncanonical Wnt cascade,
      suggesting that beta-catenin/TCF-dependent gene transcription has to be curtailed
      to allow normal tubular differentiation. Second, heterozygote deletions of Bardet
      Biedl syndrome proteins affect neural tube closure and disrupt the cochlear
      sterociliary bundles, two typical planar cell polarity defects. Third, tubular
      epithelial cells undergo oriented cell division during tubular elongation, along
      the axis of the anterior-posterior axis of the nephron. Thus, the cilium or the
      basal body/centrosome complex may provide the spatial cues to position the
      centrosome and the mitotic spindle before the next cell division. Failure to
      communicate this spatial information may condemn the tubular epithelial cells to
      proliferate and to form cysts.

PMID- 16816848
TI  - Cochrane reviews on dietary advice for reducing intakes of fat and salt.

PMID- 16816845
TI  - A clinical drug library screen identifies astemizole as an antimalarial agent.
AB  - The high cost and protracted time line of new drug discovery are major roadblocks
      to creating therapies for neglected diseases. To accelerate drug discovery we
      created a library of 2,687 existing drugs and screened for inhibitors of the
      human malaria parasite Plasmodium falciparum. The antihistamine astemizole and
      its principal human metabolite are promising new inhibitors of chloroquine
      sensitive and multidrug-resistant parasites, and they show efficacy in two mouse
      models of malaria.

PMID- 16816850
TI  - [Application of single radial hemolysis technique for diagnosis of influenza A
      (H5N1)].
AB  - BACKGROUND: To understand the optimal condition of single radial hemolysis (SRH)
      for diagnosis of avian influenza A (H5N1) virus in order that SRH could be
      performed in general laboratories. METHODS: The effect of different concentration
      of virus and species of red blood cells, as well as kind and concentration of
      agarose on testing sensitivity of SRH was determined. Meanwhile the sensitivity
      and specificity of this method were compared with those of micro-neutralization
      test. RESULTS: The optimal condition of SRH included the viral concentration of
      1000 HA units per 0.1 ml packed chicken red blood cells, the agarose
      concentration of 1.0%, the compliment added into agarose-virus-rbc slides after
      diffusion of sera. The sensitivity and specificity of SRH were very similar to
      those of micro-neutralization test. Meanwhile, no cross reaction between
      antibodies, especially antibodies against N1 antigens, H5N1 and H1N1 viruses was
      detected. CONCLUSION: The sensitivity and specificity of SRH were very similar to
      those of micro-neutralization assay. SRH could be performed in normal
      laboratories and be used for testing large scale serum samples.

PMID- 16816851
TI  - [Analysis of human H5N1 virus hemagglutinin gene isolated from the mainland of
      China].
AB  - BACKGROUND: To analyze the genetic and antigenic characteristics of human H5N1
      virus isolated from the mainland of China. METHODS: The hemagglutinin (HA) gene
      of human H5N1 virus were sequenced and analyzed. RESULTS: The results of HA gene
      sequencing showed that all the virus isolates belong to the same group because of
      the high similarity, but they were different from the virus isolated from
      Thailand and Vietnam. The sequence data also showed that the receptor specificity
      and the connecting peptide between HA1 and HA2 are still avian influenza origin.
      CONCLUSION: The virus isolates from mainland of China until now belong to the
      same group and are different from the virus isolated from Thailand and Vietnam,
      and there is no evidence showing the human-avian influenza reassortant and
      recombination.

PMID- 16816852
TI  - [Antigenic and genetic study of influenza virus B circulated in China in 2004
      2005].
AB  - BACKGROUND: To analyze the genetic and antigenic characteristics of hemagglutinin
      (HA) gene of human influenza B virus isolated from the mainland of China since
      2004-2005. METHODS: The single-way hemagglutinin inhibition (HI) tests were used
      to test the antigenic characteristics, and the HA1 gene was sequenced based on
      the antigenic results. RESULTS: The Yamagata-like and Victoria-like viruses co
      circulated in 2004-2005. For the Yamagata-like virus, the single-way HI results
      showed that 3.7% and 4.5% of the viruses had 4-fold greater HI titer difference
      compared with B/Shanghai/361/02 in 2004 and 2005, respectively. The HA1 sequence
      data showed that the virus had amino acid mutation, and there was one more
      glycosylation site at 196th site. For the Victoria-like virus, the single-way HI
      results showed that 8.5% and 20.6% of the viruses had 4-fold greater HI titer
      difference compared with B/Hong kong/330/01 in 2004 and 2005, respectively. The
      HA1 sequence data showed that the virus had replacement of 9 amino acids, and
      there was one more glycosylation site at 197th site. CONCLUSION: The results
      showed that influenza B viruses had changed antigenic and genetic characteristics
      compared with B/Shanghai/361/02, B/Hong kong/330/01 in 2004-2005.

PMID- 16816853
TI  - [Laboratory diagnoses of the first confirmed human case of avian influenza A
      (H5N1) in the mainland of China].
AB  - BACKGROUND: To determine the etiologic agent of an atypical pneumonia human case
      admitted to Xiangtan City hospital, Hunan Province in Oct. 2005. METHODS: The
      patient's respiratory tract samples and serum were collected. Throat swabs were
      tested by microneutralization and hemagglutination-inhibition assays. RESULTS:
      The results of nucleic acid detection of all respiratory samples were negative
      and virus isolation was also negative. The H5-specific antibodies of
      convalescence showed a 4-fold greater rise than acute phase. CONCLUSION: The
      atypical pneumonias case was confirmed as the first human case of avian influenza
      A (H5N1) infection in the mainland of China.

PMID- 16816854
TI  - [Establishment of molecular differential diagnostic (MDD) technology for
      detection of common respiratory viruses].
AB  - BACKGROUND: To provide rapid laboratory evidence for diagnosis of respiratory
      infection and help diagnose accurately and reduce the spread of disease, so that
      the patients can be diagnosed and treated early. METHODS: Thirteen kinds of
      respiratory viruses were detected by using Genaco's MDD technology. RESULTS: All
      the specimens were detected, the total positive rate was 100%; the sensitivity of
      the method was 10e2 (pfu/ml). CONCLUSION: The MDD system can distinguish the 13
      respiratory viruses, which helps diagnosis of respiratory viral infection.

PMID- 16816855
TI  - [Adamantane resistance among influenza A (H3N2) viruses isolated from the
      mainland of China].
AB  - BACKGROUND: To study the incidence of adamantane resistance among influenza A
      (H3N2) viruses isolated from the mainland of China since 1989 through our
      influenza surveillance system, and to provide more information for the clinical
      usage of adamantane drugs. METHODS: Totally 584 influenza A (H3N2) virus strains
      were randomly selected from our surveillance network since 1989, the adamantane
      drug resistance related gene M2 of all 584 strains was sequenced, and the drug
      sensitivity of viruses was also assayed by using biological methods in cells.
      RESULTS: No adamantane resistant strains were detected among the strains isolated
      from 1989 to 1999, but there was a surprisingly increased resistance rate of 56%
      in 2003 compared with 3.4% in 2002, and in 2005 the resistance rate increased to
      77.6%. CONCLUSION: Over 50% of virus among the strains isolated showed adamantane
      resistance since 2003, and the incidence rate is increasing.

PMID- 16816856
TI  - [Development of methods for detection of H5N1 from human clinical specimens].
AB  - BACKGROUND: To establish a method for H5N1 RNA detection and laboratory diagnosis
      of suspected human avian influenza (H5N1) virus infected cases. METHODS: The
      typing and sub-typing primers were designed according to M and H5 and N1 gene
      respectively, and the RT-PCR and real-time PCR were developed using these
      primers. RESULTS: The RT-PCR and real-time PCR could be used for H5N1 detection
      specifically, and there was no cross reaction with other influenza subtypes such
      as H1 and H3. The sensitivity for RT-PCR and real-time PCR was 1 TCID50 and 0.01
      TCID50 respectively. Thirteen laboratory confirmed human H5N1 cases were detected
      from 42 suspected cases by using these methods. CONCLUSION: The established RT
      PCR and real-time PCR methods can be used for laboratory detection of suspected
      human H5N1 cases.

PMID- 16816857
TI  - [Antigenic and genetic study of influenza virus (H1N1) circulated in China in
      2004-2005].
AB  - BACKGROUND: To analyze the genetic and antigenic characteristics of hemagglutinin
      (HA) gene of human influenza (H1N1) virus isolated from the mainland of China
      since 2004 to 2005. METHODS: The single-way hemagglutination inhibition (HI)
      tests were used to test the antigenic characteristics, and the HA1 gene was
      sequenced based on the antigenic results. RESULTS: The single-way HI results
      showed that no virus isolates had 4-folds greater HI titer compared with
      A/Shanghai/1/1999 (H1N1) in 2004, but there was 6.3% virus had 4-fold greater
      difference in 2005. The HA1 sequence data showed that the H1N1 virus had the
      following amino acid mutations such as 54 K > R, 90 T > K, 101 Y > H, 149 R > K,
      169 V > A, 190 D > N, 212 R > K, 219 K > R, 245 W > R, 246 Y > F, 258 T > N, 318
      V > A and the 54 and 190 amino acids located in antigenic group of HA1.
      CONCLUSION: The H1N1 virus was changing in antigenic and genetic characteristics.

PMID- 16816858
TI  - [Significance of detection of serum sialic acid and Epstein-Barr virus VCA-IgA in
      diagnosis and monitoring radiotherapy effectiveness in nasopharyngeal carcinoma
      patients].
AB  - BACKGROUND: To understand the significance of detection of serum sialic acid (SA)
      and Epstein-Barr virus VCA-IgA (EBV-CA-IgA) in diagnosis and monitoring
      radiotherapy effectiveness of nasopharyngeal carcinoma (NPC) patients. METHODS:
      Serum SA and EBV-CA-IgA were detected in 65 cases with NPC before radiotherapy
      and one months after radiotherapy and 21 cases one year after radiotherapy for
      NPC with local recurrence and/or distant metastasis. Healthy persons and patients
      with benign lesions of head and neck were also enrolled as control group.
      RESULTS: SA and EBV-CA-IgA of NPC patients before radiotherapy were significantly
      higher than those in control group (P<0.01). The sensitivity of combination of SA
      and EBV-CA-IgA (96.9%) was higher than those determined alone (P<0.05). The SA
      level of NPC patients after radiotherapy and without recurrence after
      radiotherapy was reduced significantly compared to the NPC patients before
      radiotherapy (P<0.01). The SA level of NPC patients with recurrence was
      significantly higher than that in NPC patients without recurrence (P<0.01),
      whereas the positive rate of EBV-CA-IgA changed little. CONCLUSION: Dynamic
      detection of serum SA may be a valuable technique for diagnosis and monitoring
      radiotherapy effectiveness in NPC patients. The combined determination of the two
      indexes can raise the positive rate of patients with NPC.

PMID- 16816859
TI  - [Expression of the human papillomavirus type 16L/E7 fusion protein in E. coli and
      observation of its immunogenicity in mice].
AB  - BACKGROUND: Many epidemiological and experimental evidences prove that cervical
      cancers are strongly associated with genital high-risk types of human
      papillomavirus (HPV). HPV16 is present in 50% of the tumor specimens. Thus, it is
      important to develop vaccines against HPV16 and cervical cancer. The authors
      studied the expression of the HPV16 L1DeltaCE7N fusion protein in E. coli and
      observed its immunogenicity. METHODS: The fragment of HPV16 L1DeltaC gene and the
      E7N gene were amplified by PCR separately; the fusion gene named L1DeltaCE7N was
      generated by fusing E7N to the C terminal of L1DeltaC then the chimeric gene was
      cloned into prokaryotic expression vector pGEX-2T and expressed in E. coli strain
      JM109. The L1DeltaCE7N protein expressed were detected by Western blot. Finally
      its immunogenicity was characterized in immunized mice. RESULTS: It was proved
      that the sequence and open reading frame of fusion gene L1DeltaE7N was correct by
      sequencing; SDA-PAGE gel analysis showed that HPV16 L1/E7 fusion protein was
      highly expressed in E. coli; the protein was expressed as soluble form and the
      molecular weight was about 85 x 10(3). The fusion protein could be purified by
      affinity chromatography and gel filtration. The ELISA result indicated that L1/E7
      could elicit specific antibodies against L1 and E7 in immunized mice. In vivo
      tumor protection test indicated that tumor formation was retarded or prevented in
      the mice after vaccination with L1/E7, when C57 BL/6 mice were challenged by
      syngeneic HVP16E6 and E7 transformed tumor cells. CONCLUSION: HPV16L1/E7 fusion
      protein was expressed in E. coli, it can be a candidate for prophylactic and
      therapeutic vaccine for HPV16-associated infection and tumors.

PMID- 16816860
TI  - [Expression of the hepatitis Delta antigen in prokaryotic cell and evaluation of
      its application as an EIA diagnostic reagent].
AB  - BACKGROUND: To construct the pRSETB-HDAg recombinant expression plasmid and to
      obtain soluble hepatitis D virus antigen with high biological and antigenic
      activity. METHODS: HDAg gene fragment was inserted into fusion expression pRSET B
      vector that includes T7 promoter and a polyhistidine tag. The recombinant plasmid
      was transformed into host bacterium BL21 after induction with IPTG. The
      expression supernatant was purified by chelating affinity chromatography and the
      recombinant HDAg antigenic activity was detected by EIA. RESULTS: EIA detection
      using the recombinant HDAg showed strong positive reaction with hepatitis D
      patients sera. The positive rates of the EIA, compared with HDAg from USA and Hua
      Mei EIA kit in detecting 26 cases of anti-HDV positive reference sera, were 100%,
      96.15% and 100%, respectively. CONCLUSION: Recombinant plasmid for HDAg with good
      antigenicity was successfully constructed and could be used as hepatitis D
      antibody detection reagent.

PMID- 16816861
TI  - [Efficacy, influencing factors and safety of PEG-INF alpha-2a (PEG-INF-2a) in the
      treatment of chronic hepatitis C: analysis of 89 patients].
AB  - BACKGROUND: To investigate the efficacy, influencing factors and safety of PEG
      INF alpha-2a (PEG-INF-2a) in the treatment of hepatitis C. METHODS: Totally 89
      patients with hepatitis C were included in this study and 46 patients were
      treated with PEG-INF-2a (180 microg or 135 microg/week) and RBV 900 mg/d, 43
      patients were treated with IFNalpha-2a (5 MIU/qod) and RBV 900 mg/d. The time of
      treatment was 48 weeks, and all the patients were visited 24 weeks after
      treatment. There were no significant differences between the two groups in
      pretreatment HCV-RNA, HCV genotype and other clinical data. The main parameters
      to evaluate the efficacy were virological and biochemical responses. The side
      effects were intensively observed. RESULTS: Sustained virological response (SVR)
      rate in PEG-IFNalpha-2a group was significantly higher than that in IFNalpha-2a
      group (56.5% and 19.5% respectively, P<0.001). As the patients were divided
      according to HCV genotype 1 and high virus load, the SVR rate of PEG-INF alpha-2a
      group was higher than IFNalpha-2a group (P<0.001). However, there was no
      significant difference between two groups in the patients with non-genotype 1 and
      low viral load (P=0.664, 0.116). Similar side-effects were observed in PEG
      IFNalpha-2a group and IFNalpha-2a group, but the rate of weight decline and the
      degree of leukocyte decrease were more significant in PEG-INF alpha-2a group than
      in IFNalpha-2a group (P=0.001). CONCLUSION: The efficacy of PEG-INF alpha-2a in
      the treatment of chronic hepatitis C is superior to that of conventional IFNalpha
      2a, PEG-INF alpha-2a had good tolerance and safety profiles.

PMID- 16816862
TI  - [Screening and identification of genes trans-regulated by a novel HbeAg
      interacting protein AK026018 with microarray assay].
AB  - BACKGROUND: To investigate the biological functions of a novel hepatitis B virus
      e antigen (HbeAg) interacting protein AK026018, and to use cDNA microarray
      technique to screen genes regulated by the protein. METHODS: The AK026018 coding
      DNA fragment was amplified by reverse transcription polymerase chain reaction (RT
      PCR) technique from HepG2 cell. The expressive vector of pcDNA3.1-AK was
      constructed by routine molecular biological methods. The HepG2 cells were
      transfected with pcDNA3.1 and pcDNA3.1-AK, respectively by using lipofectamine.
      The total RNA was isolated and reverse transcribed. The cDNA of each sample was
      subjected to microarray screening with 8,464 cDNA probes and analyzed by
      bioinformatics. RESULTS: The expressive vector was constructed and confirmed by
      DNA sequencing analysis and restriction enzyme digestion. High quality mRNA and
      cDNA of transfected HepG2 cells had been prepared and successful microarray
      screening conducted. From the scanning results, there were 122 differential
      expression genes, of which 36 genes were down-regulated, and 16 genes were up
      regulated. CONCLUSION: Microarray technique was successfully used to screen the
      genes trans-regulated by AK026018. The expression of AK026018 protein affects the
      expression spectrum of HepG2 cells.

PMID- 16816863
TI  - [Clinical analysis of the infection with human papillomavirus in women].
AB  - BACKGROUND: To determine the relationship between human papillomavirus infection,
      cervical carcinoma, pre-cancerous lesion and condyloma acuminatum. METHODS: From
      January 2004 to August 2005, 1086 inpatients in department of dermatology and
      department of gynaecology and obstetrics in Southwest Hospital and No. 302
      Hospital with cervical lesions and condyloma were reviewed. All specimens were
      detected for HPV-DNA using techniques of Gene Array and fluorogenic quantitative
      polymerase chain reaction (FQ-PCR). All detections of HPV-DNA were performed in
      the first admission before the patients underwent any examination or treatment.
      RESULTS: The positive rates of HPV-DNA detection were 100% in cervical
      intraepithelial neoplasia (CIN) I, and II and cervical carcinoma. Among these,
      the main subtype was HPV 16. But some of the patients were found to be positive
      for more than 2 subtypes of HPV. While the commonest HPV subtype was HPV 18 in
      endometrial cancer. Some of the patients were detected to be positive for more
      than 2 subtypes of HPV. In 636 female patient with condyloma acuminatum, the
      infection rates of HPV6, HPV11 accounted for 44.97% and 29.40%, respectively, HPV
      16 and/or HPV 18 infection constituted a small percentage. In a few cases,
      infection with more than 2 subtypes was detected. CONCLUSION: Cervical carcinoma
      including pre-cancerous lesion differs from condyloma acuminatum in dominate
      infectious subtype of HPV. The former is mainly associated with HPV 16 and HPV 18
      infections, and the latter mainly associated with HPV 6 and HPV 11 infections.
      But in both of the above lesions, a mixed infection with more than 2 types may
      occur and make the pathological changes and clinical treatment more complicated.
      The early diagnosis and supervision of HPV infection may be of great value for
      improvement of prognosis and quality of life.

PMID- 16816864
TI  - [Reevaluation of the typing criteria for patients with chronic severe hepatitis].
AB  - BACKGROUND: To study the clinical features and more reasonable typing criteria
      for patients with chronic severe hepatitis and decompensated liver function.
      METHODS: Data of 106 cases of decompensated cirrhosis, 124 cases of chronic liver
      failure and 100 cases of chronic liver failure (chronic liver failure group I,
      CLF I) with decompensated cirrhosis (chronic liver failure group II, CLF II) were
      analyzed retrospectively. RESULTS: (1) The ages were youngest in chronic liver
      failure group I (about 30 years), and the oldest in decompensated cirrhosis group
      (about 50 years). (2) There were significant differences in albumin, globulin,
      ALT, AST, protruding activity, blood glucose, blood lipid and cholinesterase
      among the three groups. (3) There was no significant difference in upper
      digestive tract bleeding and hepatorenal syndrome, on the other hand, there was
      significant difference in ascites and hepatic encephalopathy. (4) The prognosis
      of the patients in decompensated cirrhosis group was better than that of chronic
      liver failure group I and chronic liver failure group II. CONCLUSION: The
      clinical feature and prognosis in three groups were different, so, it is
      suggested that chronic severe liver disease be divided into 2 types: one is
      chronic severe liver disease type I, which is associated with chronic hepatitis,
      and the other is chronic severe liver disease type II, which is associated with
      cirrhosis, and the typing criteria for decompensated cirrhosis remains unchanged.

PMID- 16816865
TI  - [Full length nucleotide sequence analysis of L and M segments of Hantavirus Q32
      strain gene].
AB  - BACKGROUND: To study the full length L and M sequence of Hantavirus Q32 strain
      gene and explore its molecular characters. METHODS: The L and M segment cDNA of
      Hantavirus Q32 strain was amplified by RT-PCR. The purified PCR products were
      sequenced directly or cloned into pGEM-T Vector and then sequenced. RESULTS: The
      L genome segment of Q32 virus was found to be 6533 nucleotides in length. One
      large open reading frame was found located at bases 38 to 6493. This was
      predicted to encode an L protein 2151 amino acids in length with a molecular mass
      of 2.46 x 10(5). The M genome segment was 3616 nucleotides in length. One open
      reading frame was located at bases 41 to 3488. This was predicted to encode an M
      protein 1135 amino acids with a molecular mass of 1.26 x 10(5). CONCLUSION: The
      nucleotides sequence of M and L segments of strain Q32 was similar to that of
      other Hantavirus M and L segments. Deduced amino acid sequences of glycoprotein
      and RNA polymerase revealed high homologue to other Hantavirus.

PMID- 16816866
TI  - [Prevalence of anti-human parvovirus B19 IgG antibody among blood donors in Jilin
      province].
AB  - BACKGROUND: To investigate the prevalence of the parvovirus B19 infection among
      the blood donors in Jilin province to provide the basic data to evaluate the
      epidemics of B19 virus in China. METHODS: Indirect ELISA was used to detect IgG
      antibody against parvovirus B19 in the sera from blood donors. RESULTS: In a
      total of 184 serum samples, IgG antibody was detected in 55.43% samples, antibody
      positive rate in female was significantly higher than that in male (P<0.05) and
      the positive rate peaked at 35-45 years age group. CONCLUSION: These data
      illustrate that the prevalence of the B19 antibody in blood donors of Jilin
      province was high, and it is therefore necessary to detect the B19 DNA to ensure
      the blood safety.

PMID- 16816867
TI  - [Immune responses in rhesus induced by recombinant adenovirus Ad-LMP2].
AB  - BACKGROUND: To observe the LMP2 specific cellular and humoral immune responses
      after immunization with recombinant adenovirus Ad-LMP2 in rhesus. METHODS: The
      rhesuses were immunized with Ad-LMP2 through intra muscular injection in three
      groups, high dosage (4.5 x 10(11) VP/kg), medium dosage (1.5 x 10(11) VP/kg) and
      low dosage (0.5 x 10(11) VP/kg) groups. They were totally immunized six times at
      intervals of 5 days. The specific cellular immune responses were tested during
      the 7th week by ELISPOT after immunization. And the titers of anti-LMP2 antibody
      were tested by EIA throughout the period of immunization. RESULTS: LMP2 induced
      specific cellular and humoral immune responses in all three dosage group. The
      potency of immune responses was related with the dosage of immunization. Higher
      dosage elicited more potent immune response. Both the neutralizing antibody to
      adenovirus and anti-LMP2 antibody could be detected from 2 weeks after
      immunization. They would reach the peak during 3-4 weeks after immunization, then
      declined during the 7th week after immunization. CONCLUSION: The recombinant
      adenovirus LMP2 could induce specific cellular and humoral responses in rhesus
      after immunization.

PMID- 16816868
TI  - [Identification and typing of human enteroviruses using an RT-PCR assay].
AB  - BACKGROUND: To establish a molecular detection and typing assay for
      identification and typing of human enteroviruses (HEV) which is suitable for
      clinical detection and epidemiologic research. METHODS: Using both primers
      specific for HEV genus and HEV typing primers and reverse transcription
      polymerase chain reaction (RT-PCR) the authors detected preliminarily HEV by
      agarose gel electrophoresis and then identified serotype through nucleotide
      sequence analysis of RT-PCR amplicons. The monospecific antisera neutralization
      was applied to validate the typing results. RESULTS: The serotype of 18
      suspicious HEV samples was identified: 4 Coxsackievirus type A24 (CVA24), 3 CVB3,
      1 CVB2, 1 CVA9, 1 CVA15, 1 Echovirus type 3 (E3), 1 E6, 1 E9, 1 E11, 1 E14, 1 E33
      and 1 Rhinovirus type 9. The result was validated by monospecitive antisera
      neutralization. CONCLUSION: This RT-PCR assay for HEV detection and typing may be
      suitable for clinical detection and epidemic research since this method is
      sensitive and specific for direct identification and typing of HEV.

PMID- 16816869
TI  - [Epidemiologic study and HLA analysis of highly exposed to HIV but persistently
      seronegative subjects (HEPS) in commercial blood donors in China].
AB  - BACKGROUND: To investigate epidemiology and HLA typing of highly exposed to HIV
      but persistently seronegative subjects (HEPS) in commercial blood donors in
      China. METHODS: This was a cohort study for epidemiologic characteristics of
      highly exposed but persistently seronegative subjects. PCR with sequence-specific
      primer and PCR-SSP for HLA typing were applied. RESULTS: Eight HEPS were
      identified. Compared HLA typing with seropositive couple, high frequency of HLA
      a24, HLA-B40 genotyping was observed. CONCLUSION: Highly exposed to HIV but
      persistently seronegative subjects in commercial blood donors in China had high
      frequency of HLA-A24 and HLA-B40 genotype.

PMID- 16816870
TI  - [Construction of bicistronic vector and its application to combined DNA vaccine].
AB  - BACKGROUND: To study preparation of polyvalent DNA vaccine and the control of
      multiple gene expression. METHODS: A bicistronic vector pcDNA3.0BA was
      constructed from pcDNA3.0. HCV PC154 gene and HBV preS2S gene were inserted into
      this vector to form bicistronic expression construct pcDNA3.0BAPC154S2S and
      monocistronic expression construct pcDNA3.0BAPC154 or pcDNA3.0BAS2S. These
      plasmids were transiently expressed in COS-7 cells and injected into muscles of
      BALB/c mice. RESULTS: pcDNA3.0BA contains two cistronic units, which can co
      express two kinds of genes, with the first immunogen gene and the second gene
      serving as additional immunogen or as modulator for the immune responses. HBV
      surface Ag and HCV core Ag were coexpressed in vitro. The antibody responses and
      lymphoproliferation to antigens were similar between bicistronic and
      monocistronic expression construct in mice. CONCLUSION: pcDNA3.0BA is a novel
      vector, which can coexpress two proteins and elicit polyvalent immune responses.

PMID- 16816871
TI  - [Comparative study on the resistance of Bacteriophage phi chi 174D, T4 and f2 to
      an iodophor in laboratory].
AB  - BACKGROUND: To screen for the most resistant bacteriophage as indicator in
      disinfection tests, the resistance of bacteriophage phi chi 174D, T4 and f2 to
      iodophor were observed in laboratory. METHODS: The virucidal activity of iodophor
      against bacteriophage phi chi 174D, T4, and f2 were assessed by suspension test.
      The neutralizer is selected and appraised by testing with neutralizer.
      Bacteriophage phi chi 174D, T4, and f2 were detected and enumerated by the double
      agar-layer plaque technique. RESULTS: (1) With 500 mg/L of available iodine of
      iodophor solution, within a contact time of 40 min, or 750 mg/L, 10 min, or 1000
      mg/L, 5 min, the reduction of bacteriophage phi chi 174D could achieve the
      "disinfection" level [log10 inactivation value (LIV) or log10 reduction value
      (LRV) of bacteriophage phi chi 174D (log10 No-log10 Nt) was > or = 4.00 log10].
      (2) With 600 mg/L of available iodine of iodophor solution, within a contact time
      of 40 min, or 700 mg/L, 5 min, the reductions of bacteriophage T4 could achieve
      the "disinfection" level. (3) With 50 mg/L of available iodine of iodophor
      solution, within a contact time of 10 min, or 75 mg/L, 10 min, the reductions of
      bacteriophage f2 could achieve the "disinfection" level. CONCLUSION: The order of
      resistance of the above three bacteriophages to iodophor from greatest to
      smallest is as follows: bacteriophage phi chi 174D greater than bacteriophage T4
      > bacteriophage f2.

PMID- 16816872
TI  - [The promotive effects of N-nitrosopiperidine on the malignant transformation of
      the immortalized esophageal epithelium induced by human papillomavirus].
AB  - BACKGROUND: Study on the promotive effects of N-nitrosopiperidine on
      carcinogenesis process was performed, based on the immortalization of human fetal
      esophageal epithelium induced by human papillomavirus (HPV) 18E6E7 genes.
      METHODS: The immortalized esophageal epithelium SHEE was induced by HPV18E6E7.
      The cells at 17th passages were cultured in 50 ml flasks. The N-nitrosopiperidine
      (NPIP) 0, 2, 4, 8 mmol/L added to the cultured medium of SHEE cells for 3 weeks.
      The morphology, proliferation and apoptosis of the cells were studied by phase
      contrast microscopy and flow cytometry. Modal number of chromosomes was analyzed
      by standard method. Tumorigenicity of the cells was assessed by soft agar colony
      formation and by transplantation of cells into nude mice. Expression of HPV was
      detected by Western blot. RESULTS: When cells were exposed to high concentration
      (8 mmol/L) of NPIP, cell death was increased, leaving a few live cells. In normal
      cultural medium instead of NPIP proliferative status of the cells restored after
      4 weeks and the cells progressed to the proliferation stage with continuous
      replication and atypical hyperplasia. At the end of the 8th week, the cells
      appeared with large colonies in soft-agar and tumor formation in transplanted
      nude mice. When the cells were cultured in 2, 4 mmol/L NPIP the doubling passage
      was delayed and without tumor formation in transplanted nude mice. Modal number
      of chromosomes was 61-65, in 8 mmol/L NPIP group and control group, 56-61.
      Expression of HPV18 appeared in experimental and control groups. CONCLUSION: NPIP
      promotes malignant change of the immortalized esophageal epithelial cells induced
      by HPV18E6E7. HPV18E6E7 synergy with NPIP will accelerate malignant
      transformation in esophageal epithelium.

PMID- 16816873
TI  - [Comparison of homemade and imported HbsAg ELISA kits on screening blood
      samples].
AB  - BACKGROUND: To evaluate homemade and imported HbsAg ELISA kits on screening blood
      donors. METHODS: Samples for evaluation included 120 HbsAg serum plates for the
      golden criteria and 400 sets of serum from blood donors in Dongguan. The samples
      underwent blind screening with homemade and imported ELISA kits respectively.
      RESULTS: The sensitivity of homemade (Xinchuang) and imported (Diasorin) HbsAg
      ELISA kit were 85.71% (72/84) and 100% (84/84), respectively. Their specificity
      was 100% (436/436) and 96.55% (421/436) respectively. The consistency of two
      ELISA kits was 100%. CONCLUSION: The imported ELISA kit had the highest
      sensitivity, but its specificity was not as good as that of homemade ELISA kit.
      The two kinds of ELISA kits had good repetition. The combination of the two
      reagents may ensure the safety of blood transfusion.

PMID- 16816874
TI  - [Follow up study on viruses associated with SARS among the SARS patients].
AB  - BACKGROUND: To study the existence status of the SARS-CoV, retrovirus, and the
      poliovirus in the bodies of the patients with SARS and the possible relationship
      between the three viruses and SARS. METHODS: The clinical specimens of the
      nasopharyngeal swabs, sputum (or saliva), urine, fecal specimens were collected
      on three consecutive days from 8 patients with SARS 2 years after the recovery
      from SARS. SARS-CoV, reovirus and poliovirus RNA was detected by using reverse
      transcription (RT)-PCR; IgG antibody to the poliovirus type 1 and 3 and the
      antibody to SARS-CoV were determined using enzyme linked immunosorbent assay
      (ELISA). RESULTS: All the specimens were negative for SARS-CoV and reovirus by RT
      PCR, but the fecal specimens from 4 persons were positive for poliovirus. The
      sequences of these poliovirus were highly homologous to that of human poliovirus
      type 1 strain sabin 1 genome at nucleotide level, but back mutations have
      occurred in the primary attenuating mutation sites at nucleotide position 480 (G 
      -> A) in the 5' UTR and the nucleotide position 2795 (A --> G). No SARS-CoV,
      reovirus, and poliovirus were found in the normal controls. Three serum specimens
      were positive for the antibody to SARS-CoV. The IgG antibody to poliovirus were
      detected in 4 SARS patients and 23 healthy persons. No positive results for
      antibody to SARS-CoV were detected in the 25 healthy persons. CONCLUSION: The
      positive rate of the poliovirus antibody in the serum of SARS patients 2 years
      after recovery was significantly different from that of the normal controls, and
      the positive rate of poliovirus in the fecal specimens was still very high, and
      more importantly back mutations have occurred in the attenuating mutation sites
      at nucleotide position which plays an important role in the poliomyelitis.

PMID- 16816875
TI  - Treatment of hypertension in patients with congestive cardiac failure.
AB  - Hypertension is a major risk factor for the development of cardiac failure.
      Patients with severe heart failure and left ventricular ejection fraction <40%
      are excluded from the majority of hypertension trials. The European Guidelines
      recommend treatment of hypertension in patients with heart failure and the
      introduction of blood pressure-lowering drugs that deal with the underlying
      disease. Several of the drugs may be needed in combination to achieve target
      blood pressure.

PMID- 16816876
TI  - Stem cell therapy in heart failure: where do we stand and where are we heading?
AB  - Heart failure is a multifactorial and complex debilitating disease facing
      limitations in available pharmacological therapeutics. To cure such a disease,
      cardiac regeneration has been envisioned using stem cells. A few clinical trials
      using bone marrow-derived stem cells have been carried out without conclusive
      results. Stem cells of other origins should therefore be considered for future
      trials. In this article, the advantages and disadvantages of the most promising
      stem cells to be used in cell therapy are reviewed. The remaining challenges of
      cell therapy of heart failure are also presented.

PMID- 16816877
TI  - Current thinking regarding the use of diuretics in heart failure.
AB  - The majority of therapies used in the contemporary management of chronic heart
      failure (CHF) have been rigorously evaluated by means of large-scale clinical
      trials to assess their beneficial effects on quality of life and prognosis. Such
      therapies include angiotensin-converting enzyme (ACE) inhibitors, beta-blockers,
      and cardiac resynchronization therapy (CRT). Diuretics are the most commonly
      prescribed class of drugs in CHF patients and in the short term they remain the
      most efficacious treatment for relief from fluid congestion. There is, however,
      scant evidence to suggest that they confer any long term benefit in terms of
      disease progression or prognosis to the CHF sufferer. Injudicious use of
      diuretics has been demonstrated to be potentially harmful and consideration
      should be paid to avoiding dietary salt indiscretion as well as the
      pharmacokinetic properties of individual diuretics to achieve optimal diuretic
      response. In this article, we explore the current insight into the use of
      diuretics in CHF.

PMID- 16816880
TI  - [Apathy in Alzheimer's disease].
AB  - Apathy is the most common neuropsychiatry syndrome in Alzheimer's disease
      affecting 30-60% of patients. It can be defined as a loss of motivation and
      manifests in affect, cognition and behavioral changes, determining blunted
      emotional response, lack of insight and social retraction, respectively. In this
      paper, the clinical features and the therapeutic perspectives of apathy are
      presented. There is considerable overlap between apathy and depression in
      Alzheimer's disease, but both are considered discrete syndromes. Pharmacological
      interventions for apathy include psychostimulants, such as methylphenidate,
      dopaminergic agents and cholinesterase inhibitors, but the results are
      controversial and there is no established treatment.

PMID- 16816882
TI  - Factors for satisfaction among providers of ancillary health services in a
      community-based cancer prevention program: a pilot study in Nevada.
AB  - Providers of ancillary health services are essential members of any health care
      delivery system. They supply laboratory, radiology, and other diagnostic
      modalities necessary for quality medical care. Assessment of the providers'
      factors for satisfaction in participating in cancer prevention programs can
      contribute to better services and can serve as a model for other community-based
      health programs. We conducted a pilot survey of providers of ancillary services
      in the Nevada Women's Health Connection, a community breast and cervical cancer
      prevention program. Of the 93 participating providers, a total of 44 providers
      completed the survey. We subjected the survey data to factor analysis using
      iterative principal axis factoring with Varimax rotation. Three components of
      satisfaction were identified, comprising satisfaction with the (1) reimbursement
      process, (2) positive perception of the program, and (3) familiarity with
      program's requirements. All three components accounted for 72.08% of the total
      variance before the rotation. Amount of financial gain was not a significant
      factor for satisfaction among participating providers. Providers of ancillary
      health services were satisfied in their participation in this community-based
      cancer prevention program. There were three components of satisfaction
      identified. Further attention should be given on these issues as they have
      implications for quality improvement in health services for community-based
      programs dealing with low income and uninsured patients.

PMID- 16816883
TI  - Prenatal calcification of the inferior vena cava and renal veins in a normal
      neonate.
AB  - Prenatal calcification of the inferior vena cava (IVC) and renal veins is a rare
      condition with unclear etiology and prognosis. It occurs with renal vein
      thrombosis in utero and is associated with congenital anomalies and abnormal
      prenatal hemodynamic status. We report a rare case of prenatal IVC and renal vein
      calcification in a normal neonate without any history of compromised prenatal or
      perinatal condition, or significant deterioration of kidney function.

PMID- 16816884
TI  - The perception of South African adolescents regarding primary health care
      services.
AB  - Most of the South African public health facilities fail to provide adolescent
      friendly health services. A quantitative, descriptive research study was
      conducted at Stinkwater, a rural area in Hammanskraal, South Africa. The
      objective of the study was to describe the adolescent's preferences regarding
      primary health care services. A survey was conducted among 119 adolescents. It
      was found that adolescents wished to be involved in the planning of the
      activities of the adolescent health service, and that friendliness and respect
      for adolescents were seen as desirable characteristics of an adolescent-friendly
      health care service. Adolescents preferred services to be available throughout
      the week and to be located at the school, youth center, community center,
      hospital, or clinic. Health education was indicated as a priority and the health
      care team should include different members of a multidisciplinary team.
      Adolescents preferred that their health services be separated from adult services
      and that a male nurse be employed in the adolescent service in order to create a
      less feminine image. It was also recommended that all adolescents be educated
      about the types of services available. Understanding health care service
      preferences of adolescents is needed in order to deliver optimal health care to
      this group.

PMID- 16816885
TI  - Nutcracker syndrome: a rare cause of hematuria.
AB  - Nutcracker syndrome is the compression of the left renal vein between the aorta
      and superior mesenteric artery. It is a rare cause of hematuria which results
      from the rupture of congested renal veins into the collecting system.

PMID- 16816886
TI  - Leptin levels in Henoch-Schonlein purpura.
AB  - The objective of this paper is to assess the possible role of nitric oxide (NO)
      and leptin in Henoch-Schonlein purpura (HSP). We investigated the serum leptin
      and total nitrite levels in 22 children with HSP in the acute phase and after
      remission and in 20 age- and sex-matched healthy control. Serum leptin levels
      (nanograms per milliliter; median, min-max) were statistically higher in the
      acute phase (12.9, 9.1-19.5) than those in the remission phase (6.1, 3.7-10.5,
      p<0.001) and in the control group (4.9, 3.8-7.5, p<0.001). Also, serum nitrite
      levels (micromole per liter; median, min-max) were higher in children in the
      acute phase (45.0, 32.0-60.0) compared to those in remission phase (30.5, 23.0
      48.0) and in the control group (29.5, 18.0-38.0) (p<0.001, p<0.001,
      respectively). There was a positive correlation between serum leptin and total
      nitrite levels (r=0.65, p<0.001). We have demonstrated that serum leptin and NO
      levels were increased during the acute phase in children with HSP, and returned
      to normal levels in remission. We suggest that leptin and NO may have a role in
      the immunoinflammatory process of HSP, especially in the acute phase. Further
      studies are needed to clearly establish the roles of leptin and NO in the
      pathogenesis of HSP.

PMID- 16816887
TI  - Relationship between histological subtypes and clinical characteristics at
      presentation and outcome in biopsy-proven temporal arteritis. Identification of a
      relatively benign subgroup.
AB  - Temporal arteritis (TA) may offer major complications, whilst high dosage of
      prednisone may result in serious side effects. We tried to identify a subgroup of
      TA, which can be treated with a lower dosage of prednisone. Retrospectively,
      clinical and laboratory data were studied at presentation, as well as the outcome
      in 44 consecutive patients with biopsy-proven temporal arteritis. These data were
      related to three particular histological subgroups, (a) classical giant cell
      arteritis, (b) atypical arteritis, and (c) 'healed arteritis', defined according
      to Allsop and Gallagher (The American Journal of Surgical Pathology 5:317-332,
      1981). At presentation in subgroup c, erythrocyte sedimentation rate was lower
      and the level of haemoglobin was higher than in the other two subgroups. During
      follow-up in the healed arteritis group, reactivation, recurrence, or early death
      were not observed, whilst prednisone dosage after 2 and 3 years was lower
      compared to subgroup b. Major complications (permanent blindness and
      cerebrovascular accident) were only observed in subgroups a and b. We believe
      that the healed arteritis subgroup represents a relatively benign subgroup with a
      mild clinical presentation and a good prognosis. Therefore, a much lower initial
      prednisone dosage (15 mg/day) is suggested for patients in subgroup c than in the
      other two subgroups (40-60 mg/day).

PMID- 16816888
TI  - A review of the adverse effects of laser hair removal.
AB  - Laser hair removal is ever increasing in popularity. Technology is fast
      advancing, and there are increasingly excessive commercial claims that laser hair
      removal in all skin types is free of side effects. The aim of this study is to
      review the evidence from published literature regarding the incidence of adverse
      effects after laser and light systems for hair removal. A review of the current
      published literature on the ill effects reported after laser/light-assisted
      depilation was conducted. Overall incidence of adverse effects after laser/light
      hair removal appears to be low, with very uncommon permanent sequelae. The two
      largest studies to date have shown that acute and transient side effects do
      occur. Higher incidence of pigmentary alterations is associated with the shorter
      wavelength lasers (up to 19%), particularly with darker skin types, compared with
      lower incidence using the neodymium-yttrium-aluminium-garnet laser (2-3%). Both
      studies did not show any long-term side effects or scarring. Laser/light hair
      removal, carried out by trained professionals, is a safe procedure with a very
      low incidence of permanent sequelae. The majority of adverse effects are
      transient and minor. They are more common in darker skin. Longer wavelength
      devices reduce the risk in darker skin.

PMID- 16816889
TI  - The vertebral artery: know the high risk patients.

PMID- 16816890
TI  - Complex venous anomalies: magnetic resonance imaging findings in a 5-year-old
      boy.
AB  - We report magnetic resonance imaging (MRI) findings of a very unusual venous
      anomaly case. A 5-year-old boy who had surgical repair of coarctation of the
      thoracic aorta was referred to our department for evaluation of an enlarged
      venous structure anterior to the aorta, which had been noted during the surgery.
      Contrast enhanced dynamic MRI revealed partial anomalous pulmonary venous return
      to the left azygos vein, double inferior and superior vena cava with the left
      azygos continuation of the left superior vena cava. The recognition of venous
      anomalies allows correct planning of surgical and interventional procedures. MRI
      is a valuable imaging tool providing detailed anatomical information.

PMID- 16816891
TI  - The "muscular hernia sign": an original ultrasonographic sign to detect lesions
      of the forearm's interosseous membrane.
AB  - The total disruption of the forearm's interosseous membrane can lead to an Essex
      Lopresti syndrome. The diagnosis must be done early for a better prognostic.
      Incomplete lesions can aggravate and an early diagnosis of incomplete lesions is
      a challenging problem. Magnetic resonance imaging is the gold standard but
      remains expensive, and is hard to obtain in an emergency. On the contrary,
      ultrasonography is cheap, accessible in an emergency, and dynamical tests can be
      performed easily. Twelve fresh frozen forearms were randomized in four groups.
      The membrane was divided into three parts (proximal, middle, and distal thirds).
      Each group was prepared with variable patterns of lesions. Two radiologists
      performed an ultrasonographic (US) examination of these forearms. They were
      blinded with respect to the lesional status of the forearms. Each examination
      consisted of two stages: static and dynamic. During the dynamic examination, the
      radiologist looked for the "muscular hernia sign". The results of their
      examinations were compared with the real lesional status. The static examination
      was very efficient in the proximal and middle parts of the membrane, and less
      reliable in the distal third. With the dynamical examination, no mistake occurred
      at the proximal and middle parts of the forearm, and there was only one at the
      distal part. The US examination of the interosseous membrane is very efficient to
      detect incomplete lesions, mostly, if dynamical tests are performed looking for a
      "muscular hernia sign".

PMID- 16816893
TI  - Optimal production of poly-gamma-glutamic acid by metabolically engineered
      Escherichia coli.
AB  - Metabolically-engineered Escherichia coli strains were developed by cloning poly
      gamma-glutamic acid (gamma-PGA) biosynthesis genes, consisting of pgsB, pgsC and
      pgsA, from Bacillus subtilis The metabolic and regulatory pathways of gamma-PGA
      biosynthesis in E. coli were analyzed by DNA microarray. The inducible trc
      promoter and a constitutive promoter (P(HCE)) derived from the D-amino acid
      aminotransferase (D-AAT) gene of Geobacillus toebii were employed. The
      constitutive HCE promoter was more efficient than inducible trc promoter for the
      expression of gamma-PGA biosynthesis genes. DNA microarray analysis showed that
      the expression levels of several NtrC family genes, glnA, glnK, glnG, yhdX, yhdY,
      yhdZ, amtB, nac, argT and cbl were up-regulated and sucA, B, C, D genes were down
      regulated. When (NH(4))(2)SO(4 )was added at 40 g/l into the feeding solution,
      the final gamma-PGA concentration reached 3.7 g/l in the fed-batch culture of
      recombinant E. coli/pCOpgs.

PMID- 16816892
TI  - Intraoperative applications of the H-reflex and F-response: a tutorial.
AB  - Traditional intraoperative monitoring of spinal cord function involves the use of
      three techniques: 1. Orthodromic ascending somatosensory evoked potentials
      (SSEPs) and 2. antIDromic descending neurogenic somatosensory evoked potentials
      (DNSSEPs) monitor long-tract sensory function. SSEPs and DNSSEPs do not monitor
      interneuronal gray matter function. 3. Transcranial motor evoked potentials
      (TMEPs) monitor descending long-tract motor function and measure interneuronal
      gray matter function by activating motor neurons. TMEPs activate from 4-5% of the
      motor neuron pool. When using TMEPs 95-96% of the motor spinal cord systems
      activating the motor neurons are not monitored. Our ability to interact with our
      environment involves not only intact sensation and strength, but also complex
      coordinated motor behavior. Complex coordinated motor behavior is controlled by
      groups of electrically-coupled spinal cord central pattern generators (CPGs). The
      components of CPGs are: descending and propriospinal systems, peripheral input,
      and segmental interneurons. The point-of-control is the level of excitation of
      interneurons, which is determined by the integrated activity of the other
      components. Spinal cord injury (SCI) changes segmental reflex gain by uncoupling
      these components. Changes in gain are detected by recordings from muscles. SSEPs,
      DNSSEPs and TMEPs provIDe limited information about the status of CPGs. H
      reflexes measure the function of from 20-100% of the motor neuron pool. F
      responses measure the function of from 1-5% of the motor neuron pool. H-reflexes
      and F-responses provIDe information about the degree of coupling between CPG
      components. Recording H-reflexes and F-responses together with SSEPs and TMEPs
      not only monitors spinal cord long-tract function, but also provIDes a multiple
      systems approach that monitors those spinal cord systems that are responsible for
      the control of complex coordinated motor behavior. The objective of this paper is
      to describe how H-reflexes and F-responses can be used to monitor complex
      coordinated motor behavior.

PMID- 16816894
TI  - Pro-antibiotic substrates for the identification of enantioselective hydrolases.
AB  - A new growth-based screening method for the identification of enantioselective
      hydrolases, such as lipases and esterases, using pro-antibiotic substrates was
      devised. An enantioselective hydrolase could be identified by measuring growth
      rates of cells in liquid media containing (R)- or (S)-2-phenylbutyric
      chloramphenicol esters. This method can be applied to the screening of novel
      enantioselective microbes and to the high-throughput screening for the directed
      evolution of enantioselective hydrolytic enzymes.

PMID- 16816895
TI  - Sendai virus infection up-regulates trypsin I and matrix metalloproteinase-9,
      triggering viral multiplication and matrix degradation in rat lungs and lung L2
      cells.
AB  - To elucidate the virus-host cell interaction, we analyzed quantitatively the
      expression of various cellular proteases and tumor necrosis factor-alpha (TNF
      alpha) after Sendai virus infection in rat lungs and lung L2 cells. After
      infection, TNF-alpha mRNA levels increased rapidly to a peak on day one, and then
      trypsin I and matrix metalloproteinase (MMP)-9, but not MMP-2, were significantly
      up-regulated with a peak on day 2 in vivo. These up-regulations were confirmed in
      L2 cells. Up-regulation of proMMP-9 and its active convertase trypsin I seems to
      synergistically enhance virus multiplication and the destruction of lung matrix,
      resulting in the progression of pneumonia.

PMID- 16816896
TI  - One stroke--two triggers.

PMID- 16816897
TI  - Taenia solium DNA is present in the cerebrospinal fluid of neurocysticercosis
      patients and can be used for diagnosis.
AB  - Neurocysticercosis is the most frequent parasitic infection of the CNS and the
      main cause of acquired epilepsy worldwide. Seizures are the most common symptoms
      of the disease, together with headache, involuntary movements, psychosis and a
      global mental deterioration. Absolute diagnostic criteria include the
      identification of cysticerci, with scolex, in the brain by MRI imaging. We
      demonstrate here, for the first time, that T. solium DNA is present in the
      cerebrospinal fluid of patients. The PCR amplification of the parasite DNA in the
      CSF enabled the correct identification of 29/30 cases (96.7 %). The PCR diagnosis
      of parasite DNA in the CSF may be a strong support for the diagnosis of
      neurocysticercosis.

PMID- 16816899
TI  - Modern laparoscopy and the archery episode in the greatest epic of India:
      Mahabarata.
AB  - The laparoscopic surgeon is trained to acquire advanced skills to perform the
      complicated laparoscopic surgery of the target tissue in a three-dimensional (3D)
      space by viewing its two-dimensional (2D) video image. This technique finds its
      parallel in a very ancient archery episode portrayed in the longest and the
      greatest Indian epic, Mahabarata. In this epic, Arjuna, the master archer, is
      required to employ the strategy of aiming at the eye of a target fish rotating
      above his head by viewing its reflected image below in water; of course, all this
      to win the hand of a beautiful princess! Arjuna is so trained that he cannot but
      excel in focusing his attention on his target. A comparative study of the
      laparoscopic surgeon and the ancient master archer is done in this paper with a
      view to throwing light on the interesting similarities between the archer and the
      modern laparoscopic surgeon with respect to training methods, skills, and
      techniques.

PMID- 16816902
TI  - Neurological manifestation of tick-borne encephalitis.

PMID- 16816898
TI  - Laparoscopic surgery--15 years after clinical introduction.

PMID- 16816903
TI  - Utility of delayed spinal cord injury rehabilitation: an Italian study.
AB  - The objective was to examine the utility of delayed spinal cord injury
      rehabilitation. The design was a retrospective study in the spinal unit of a
      large rehabilitation hospital. The participants were 117 patients at their first
      rehabilitation admission with an event to admission time of 90 days or more. The
      main outcome measures were the Barthel Index, Rivermead Mobility Index, Walking
      Index for Spinal Cord Injury and motor scores at admission and discharge;
      relative changes were examined. Patients showed a significant increase in all the
      outcome measures and achieved independence or assisted independence; significant
      neurological improvement and improvement in walking were recorded too; most of
      the patients were discharged home. The present data demonstrate the utility of
      delayed rehabilitation and highlight the importance of having rehabilitation in a
      specialised setting.

PMID- 16816904
TI  - Validation of the Swedish version of the disease-specific Myasthenia Gravis
      Questionnaire.
AB  - The aim of this study was to translate and validate the disease-specific patient
      derived Myasthenia Gravis (MG) Questionnaire to enable use among Swedish MG
      patients. The original Italian version of the MG Questionnaire (MGQ) was
      translated into Swedish and transculturally adapted. The validity and reliability
      was tested on 48 Swedish MG patients. We correlated MGQ scores with disease
      severity and with the Swedish version of the Short-Form 36-item general health
      survey (SF-36). Reproducibility was assessed on 18 clinically stable MG patients.
      A significant correlation regarding the MGQ scores was seen when correlated with
      physical scores of the SF-36 and the overall clinical status. Internal
      consistency and reproducibility was excellent. We conclude that the evaluation
      capacities of the Swedish MGQ are equivalent to those of the original Italian
      version of the MGQ. The questionnaire was successfully validated as an outcome
      measure also for Swedish MG patients, which is important for international
      multicentre clinical trials.

PMID- 16816905
TI  - Two new families with hereditary essential chin myoclonus: clinical features,
      neurophysiological findings and treatment.
AB  - Hereditary essential chin myoclonus (HECM) is a rare movement disorder
      characterised by involuntary and irregular twitches of the chin. It can be
      considered a benign, focal variant of hereditary essential myoclonus. We studied
      two families that had several members suffering from HECM. Both families showed
      an autosomal dominant transmission with incomplete penetrance. Extensive
      neurophysiological studies were carried out on three patients. The results
      confirmed the myoclonic nature of phenotypical appearance and allowed
      identification of the subcortical origin of the myoclonus. The neurophysiological
      mechanisms underlying HECM are still unknown. It is supposed that pontine
      reticular formation, not controlled by superior centers, may be responsible of an
      abnormal activation of motor neurons innervating mentalis muscle. We treated
      three patients with periodic injections of botulinum toxin; a complete
      disappearance of chin myoclonus improved their quality of life.

PMID- 16816906
TI  - Size frequency distributions of the florid prion protein aggregates in variant
      Creutzfeldt-Jakob disease follow a power-law function.
AB  - The objective was to test the hypothesis that the size frequency distributions of
      the prion protein (PrP) plaques in cases of variant Creutzfeldt-Jakob disease
      (vCJD) follow a power-law function. The design was a retrospective
      neuropathological study. The patients were 11 cases of clinically and
      neuropathologically verified vCJD. Size distributions of the diffuse and florid
      type plaques were measured in several areas of the cerebral cortex and
      hippocampus from each case and a power-law function fitted to each distribution.
      The size distributions of the florid and diffuse plaques were fitted successfully
      by a powerlaw function in 100% and 42% of brain areas investigated respectively.
      Processes of aggregation/disaggregation may be more important than surface
      diffusion in the pathogenesis of the florid plaques. By contrast, surface
      diffusion may be a more significant factor in the development of the diffuse
      plaques.

PMID- 16816907
TI  - Transitory, spontaneously recovering, peripheral facial nerve palsy after
      vinorelbine administration.
AB  - Childhood intrinsic brain-stem gliomas have a dismal prognosis. Different
      treatment strategies have been adopted over the years without changing the final
      outcome of this ominous disease. Due to this grim prognosis, experimental
      therapeutic designs are worthwhile. Vinorelbine is a semi-synthetic vinca
      alkaloid that has demonstrated a broad spectrum of activity both in in vitro and
      in vivo experimental systems. By adopting vinorelbine during and after focal
      radiotherapy in the last two years, we have tried to evocate its known
      synergistic effect in brain-stem tumour control. Vinorelbine was administered
      intravenously before, during and after radiotherapy on tumour bed for a total
      duration of 10 months. All the consecutive patients whose clinical and
      radiological features corresponded to the diagnosis of an intrinsic brain-stem
      tumour, i.e., diffuse pontine glioma, have been accrued to this treatment
      protocol since July 2002. A histological assessment was not required. All
      patients were treated during hospital stay or in the outpatient clinic at the
      Istituto Nazionale Tumori of Milan (n=12) and at the Pediatric Clinic of
      Policlinico in Catania (n=1). Two of the thirteen patients so far treated have
      developed multiple subsequent, and transitory, episodes of monolateral peripheral
      facial nerve palsy during vinorelbine administration. The palsy always completely
      and spontaneously resolved at a short interval-around 30 min-after the end of the
      drug infusion. Obvious tumour progression was excluded by means of MRI; therefore
      the drug was administered as scheduled until the end of the treatment. We
      describe possible neurological and oncological implications of this unusual side
      effect, until now not reported in any other series dealing with vinorelbine as
      adjuvant treatment.

PMID- 16816908
TI  - A novel missense mutation in the L1CAM gene in a boy with L1 disease.
AB  - A novel missense mutation of the L1CAM gene (Xq28) is described in an adult
      patient affected with severe mental retardation, spastic paraparesis, adducted
      thumbs, agenesis of corpus callosum and microcephaly (L1 disease). We detected a
      transition c2308G-->A in exon 18 that caused an amino acid change in codon 770.
      The patient's mother and two sisters were heterozygous for the same mutation.
      This newly described mutation predicts the substitution of an aspartate by
      asparagine (D770N) in the second fibronectin (Fn2) domain of the extracellular
      portion of the mature L1 protein. Even if amino acid substitution does not
      significantly change the physico-chemical properties of the Fn2 domain, it seems
      clear that the integrity of this domain is required to maintain the biological
      functions of the protein. The feature peculiar to this patient is the decelerated
      head growth post-natally, leading to microcephaly. Mutations of L1CAM associated
      with prolonged survival may hamper post-natal brain and head growth.

PMID- 16816909
TI  - Creutzfeldt-Jakob disease presenting as corticobasal degeneration: a
      neurophysiological study.
AB  - Creutzfeldt-Jakob disease (CJD) can occasionally present with a clinical picture
      resembling a corticobasal degeneration (CBD). Transcallosal inhibition, as tested
      by focal transcranial magnetic stimulation, is frequently absent or highly
      disrupted in CBD patients. We report a case of CJD presenting at the beginning of
      the disease as a CBD in which the ipsilateral silent period (iSP) was present and
      well detectable. This brief report shows that study of the iSP may be a useful
      diagnostic tool in order to differentiate CBD from syndromes presenting with
      similar clinical features.

PMID- 16816910
TI  - Neurological manifestation of tick-borne encephalitis in North-Eastern Italy.
AB  - Tick-borne encephalitis (TBE) is an infectious zoonotic disease, moving from
      Central Europe to other countries and still rare in Italy. The disease, produced
      by the European subtype virus, typically takes a biphasic course with
      neurological disorders of different severity during its second phase. We report
      the first three TBE cases in Friuli Venezia Giulia (FVG), characterised by
      extremely variable clinical features. Knowledge of these different presentations
      will assist physicians in increasing their level of attention to TBE also in this
      region, where no cases of TBE had been reported in the past, despite the fact
      that it borders countries with high prevalence of the infection.

PMID- 16816911
TI  - Acute iliopsoas and adductor brevis abscesses presenting with proximal leg muscle
      weakness.
AB  - Pyomyositis is a bacterial infection of skeletal muscle. We describe the clinical
      case of a 77-year-old woman affected by gait disturbance, repetitive falls, low
      back pain and left thigh and groin pain, but without symptoms of systemic
      infection. Computed tomography and magnetic resonance imaging of the abdomen and
      pelvis showed abscesses in the left psoas and adductor brevis muscles.
      Investigations of urogenital tract and gastrointestinal system were normal.
      Systemic antibiotic treatment alone was not efficient, while surgical drainage
      improved the clinical picture. The aetiological organism, isolated from the
      abscess, was Staphylococcus aureus. We suggest that this patient had a primary
      pyomyositis rather than a secondary form. This is the first report of concomitant
      abscesses of psoas and adductor brevis muscles with early neurological
      involvement.

PMID- 16816912
TI  - Severe amnesia following bilateral medial temporal lobe damage occurring on two
      distinct occasions.
AB  - A comprehensive neuropsychological assessment was performed on a 38-year-old
      woman with drug-resistant right temporal lobe epilepsy before temporal lobectomy,
      during a 2-year follow-up period, and approximately 3 years after surgery when
      she developed a malignant glioma in the left medial temporal lobe (MTL). Both
      before and after epilepsy surgery, memory function was normal. When the tumour
      was discovered, the patient suffered from severe retrograde and anterograde
      amnesia, whereas working memory and the other cognitive abilities were preserved.
      Compared with other cases of bilateral temporal lesion, this case is peculiar
      because the damage occurred on two distinct occasions. It suggests that only one
      MTL can allow normal memory function, or can take over the function normally
      subserved by a dysfunctional contralateral MTL when the dysfunction is marked and
      prolonged, such as in chronic epilepsy.

PMID- 16816913
TI  - Epilepsy and limb girdle muscular dystrophy type 2A: double trouble,
      serendipitous finding or new phenotype?
AB  - Autosomal recessive limb girdle muscular dystrophies (LGMD) type 2A are a group
      of disorders characterised by progressive involvement of proximal limb girdle
      muscles and caused by changes in the CAPN3 gene. Involvement of tissues other
      than the skeletal muscle has not been reported so far. Here we describe the
      unusual association of LGMD2A and idiopathic generalised epilepsy in a 14-year
      old girl.

PMID- 16816914
TI  - SPIR MRI usefulness for steroid treatment management in Tolosa-Hunt syndrome.
AB  - A 40-year-old man underwent surgery for a right middle ear cholesteatoma. One
      month later, he presented with a subacute ocular pain that was followed one day
      later by the appearance of vertical diplopia attributable to a right superior
      rectus paresis, lid ptosis and hypoaesthesia in the territory of the I and the II
      right trigeminal branches. A fat-suppressed (selective partial inversion
      recovery, SPIR) gadolinium-enhanced MRI favours the detection of inflammatory
      pathological tissue inside the right cavernous sinus, and in this patient it
      suggested a diagnosis of Tolosa-Hunt syndrome. The pain disappeared quickly after
      steroid treatment was started whereas the ocular nerve involvement improved only
      slightly during the first week of treatment. After two months, the patient only
      complained of diplopia on up-gaze, but the therapy was discontinued two months
      later on the basis of both clinical signs and MRI findings. SPIR MRI may be
      useful not only to support a diagnosis of Tolosa-Hunt syndrome, but also to
      follow-up the disease course and to manage steroid treatment.

PMID- 16816915
TI  - Friedreich's ataxia: clinical heterogeneity in two sisters.
AB  - Diagnostic evaluation of two sisters affected by ataxia, with similar age of
      onset, revealed a characteristic trinucleotide expansion in the Friedreich's
      ataxia (FRDA) locus and two different phenotypic presentations. At onset the
      elder sister had retained deep tendon reflexes (FARR), while the younger sister
      presented classic FRDA. The GAA expansion in the patients' alleles proved to be
      similar in both siblings, ruling out that age at onset and clinical heterogeneity
      could be due to different FRDA mutations. On the whole, clinical and genetic data
      on these patients confirmed that FARR is a variant phenotype of FRDA.

PMID- 16816916
TI  - Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review
      of the mutations in the CYP27A1 gene.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease due to
      defective activity of the mitochondrial enzyme sterol 27-hydroxylase. In 1991,
      sterol 27-hydroxylase gene (CYP27A1) was localised on the long arm of chromosome
      2 [1]. Clinical characteristics of CTX are diarrhoea, cataracts, tendon xanthomas
      and neurological manifestations including dementia, psychiatric disturbances,
      pyramidal and/or cerebellar signs, and seizures. More than 300 patients with CTX
      have been reported to date worldwide and about 50 different mutations identified
      in the CYP27A1 gene. Almost all mutations lead to the absence or inactive form of
      the sterol 27-hydroxylase. In this review, according with the aims of this
      section of the journal, we describe the different pathogenetic mutations in the
      CYP27A1 gene and the main clinical and pathogenetic aspects that may help
      clinical neurologists in the diagnosis of CTX.

PMID- 16816919
TI  - Phosphodiesterase 4 inhibitor rolipram potentiates the inhibitory effect of
      calcitonin on osteoclastogenesis.
AB  - To assess the combination effect of calcitonin and the phosphodiesterase 4
      inhibitor rolipram on osteoclastogenesis, adherent cell-depleted bone marrow
      cells from mouse tibia and femur (ACD-BMCs), which were cultured in the presence
      of 25 ng/ml colony-stimulating factor 1 (CSF-1) and 100 ng/ml soluble receptor
      activator of NF-kappaB ligand (sRANKL), were utilized. Calcitonin inhibited
      formation of tartrate-resistant acid phosphatase-positive multinucleated cells,
      as mature osteoclasts, by 70% even at 20 pM, whereas rolipram (10 microM)
      scarcely affected osteoclast formation; in contrast, the combination of both
      agents led to significant inhibition of multinucleation and pit formation ability
      of osteoclasts. The combined administration of calcitonin and rolipram attenuated
      calcitonin receptor mRNA expression in comparison to treatment with either agent
      alone, whereas expression of RANK and CSF-1 receptor mRNAs was unchanged. Alone,
      these agents scarcely elevated intracellular cyclic AMP (cAMP) concentration;
      however, combination treatment with both agents significantly increased cAMP
      concentration in osteoclast progenitors and osteoclasts. The combination effect
      was abolished by H-89, an inhibitor of protein kinase A. It appears that rolipram
      inhibited hydrolysis of cAMP formed by calcitonin in cells and potentiated the
      inhibitory effect of calcitonin on osteoclastogenesis. The escape phenomenon
      following calcitonin treatment may also be prevented by concomitant treatment
      with the phosphodiesterase 4 inhibitor.

PMID- 16816920
TI  - Expression of osteotropic growth factors and growth hormone receptor in a canine
      distraction osteogenesis model.
AB  - Osteotropic growth factors play an important role in bone metabolism.
      Nevertheless, knowledge about their expression in relation to distraction
      osteogenesis remains limited. The aim of the present study was to determine the
      expression of growth hormone (GH), growth hormone receptor (GHR), insulin-like
      growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and bone
      morphogenetic protein 2 (BMP-2) in distraction-induced bone regeneration.
      Expression of these factors was assessed during the consolidation phase,
      comparing distraction osteogenesis with osteotomy-induced bone formation. Real
      time PCR was performed as a semiquantitative measurement of mRNA, and the
      relative expression levels of these factors were determined. In addition, plasma
      GH profiles and plasma concentrations of IGF-I, IGF-II, and insulin-like growth
      factor-binding protein 4 and -6 (IGFBP-4 and -6) were measured to assess their
      potential systemic role during bone formation. Expression of GHR, IGF-I, and BMP
      2 had significantly increased in comparison with the expression of these factors
      in mature bone. Expression of GHR was significantly higher in distraction-induced
      bone regenerate than in osteotomy-induced bone. No significant differences were
      found for the expression of IGF-I and BMP-2 between distraction and osteotomy.
      Plasma concentrations of GH, IGF-I, IGF-II, IGFBP-4, and IGFBP-6 did not
      demonstrate any significant differences between treatment groups and controls.
      Upregulation of GHR expression in distraction osteogenesis may enhance
      sensitivity to endogenous systemic GH and thus promote consolidation of the
      regenerated bone. Changes in the systemic osteotropic growth factors GH, IGF-I,
      IGF-II, IGFBP-4, and IGFBP-6 do not seem to be of importance during distraction
      osteogenesis.

PMID- 16816921
TI  - Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with
      collagen-induced arthritis (CIA).
AB  - Macrophage colony-stimulating factor (M-CSF) is a key factor for
      osteoclastogenesis at the bone-pannus interface in patients with rheumatoid
      arthritis as well as a receptor activator of NF-kappaB ligand (RANKL). Imatinib
      mesylate inhibits the phosphorylation of c-fms, a receptor for M-CSF. The present
      study investigates the effect of imatinib mesylate on joint destruction in rats
      with collagen-induced arthritis (CIA) and on osteoclastogenesis in vitro.
      Imatinib mesylate (50 or 150 mg/kg), dexamethasone, or vehicle was administered
      daily to CIA rats for 4 weeks from the onset of arthritis. Hind-paw swelling and
      body weight were measured weekly. At weeks 2 and 4, the metatarsophalangeal (MTP)
      joints and the ankle and subtalar joints were radiographically and histologically
      assessed. The effect of imatinib mesylate on osteoclast formation from rat bone
      marrow cells with M-CSF and soluble RANKL (sRANKL) in vitro was also examined.
      Radiographic assessment showed that 150 mg/kg imatinib mesylate suppressed the
      destruction of the MTP and the ankle and subtalar joints at week 2, and MTP joint
      destruction at week 4 in CIA rats, although hind-paw swelling was not suppressed.
      The number of TRAP-positive cells at the bone-pannus interface was significantly
      reduced in the group administered with 150 mg/kg imatinib mesylate compared with
      that given vehicle at week 4. Imatinib mesylate dose-dependently inhibited the
      proliferation of M-CSF-dependent osteoclast precursor cells in vitro as well as
      osteoclast formation induced by M-CSF and sRANKL. These findings suggest that
      imatinib mesylate could prevent joint destruction in patients with rheumatoid
      arthritis.

PMID- 16816922
TI  - Osteoblast differentiation is impaired in SOCS-1-deficient mice.
AB  - The suppressor of cytokine signaling-1 (SOCS-1) is a cytokine-inducible
      intracellular molecule that inhibits excessive activation of the JAK-STAT
      mediated signal cascade initiated by various stimuli. The smaller size of SOCS-1
      knockout (KO) mice suggests the presence of skeletal abnormality caused by the
      disruption of the regulatory system in JAK-STAT signaling. In addition to
      macroscopic examination, peripheral quantitative computed tomography (pQCT), bone
      histomorphometrical analysis, and in situ hybridization were used to examine the
      skeletal properties of SOCS-1 KO mice. Moreover, differentiation of primary
      cultured osteoblasts was investigated. Distinct phosphorylation of STAT1 was
      detected in the SOCS-1 KO calvarial cells but was hardly detectable in wild-type
      (WT) mice. Undercalcified areas in the skulls and sternum, as well as
      comparatively thinner calcified areas of cortical bone, were found in SOCS-1 KO
      mice. pQCT analysis showed a marked decrease in salt content, whereas the
      mineralization activity of primary cultured calvarial cells strongly suggested
      significant impairment in osteoblasts of SOCS-1 KO mice. In situ hybridization
      analysis demonstrated that these mice expressed the early markers [type I
      collagen (COL-1) and osteonectin (ON)] and the mid-marker [osteopontin (OP)] at
      levels comparable with those seen in WT mice. However, a dramatic decrease was
      observed in the expression level of the late marker [osteocalcin (OC)] of
      osteoblasts. Our findings thus demonstrate that SOCS-1 regulates osteoblast
      differentiation in the later stage.

PMID- 16816923
TI  - Immobilization decreases duodenal calcium absorption through a 1,25
      dihydroxyvitamin D-dependent pathway.
AB  - Immobilization induces significant and progressive bone loss, with an increase in
      urinary excretion and a decrease in intestinal absorption of calcium. These
      actions lead to negative calcium balance and the development of disuse
      osteoporosis. The aims of this study were to evaluate the molecular mechanisms of
      decreased intestinal calcium absorption and to determine the effect of dietary
      1,25-dihydroxyvitamin D [1,25(OH)2D] and a high-calcium diet on bone loss due to
      immobilization. The immobilized rat model was developed in the Bollman cage III
      to induce systemic disuse osteoporosis in the animals. There was a significant
      decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption
      in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D
      concentration did not change, but 1,25(OH)2D concentration decreased
      significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase
      (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha
      hydroxylase (1alpha-hydroxylase), duodenal transient receptor potential cation
      channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all
      decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or
      affect the mRNA expression of proteins related to calcium transport. Dietary
      administration of 1,25(OH)2D increased the intestinal calcium absorption that had
      been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels
      were also upregulated, resulting in prevention of the reduction in lumbar BMD.
      Therefore, it is concluded that dietary 1,25(OH)2D prevented decreases in
      intestinal calcium absorption and simultaneously prevented bone loss in
      immobilized rats. However, it remains unclear that calcium absorption and
      expression of calcium transport proteins are essential for the regulation of
      lumbar BMD.

PMID- 16816924
TI  - Direct in vitro evidence of the suppressive effect of cinacalcet HCl on
      parathyroid hormone secretion in human parathyroid cells with pathologically
      reduced calcium-sensing receptor levels.
AB  - Clinical studies have been performed to determine the effect of cinacalcet HCl
      (cinacalcet), an allosteric modulator of the calcium-sensing receptor (CaR), on
      primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism of uremia
      (SHPT). However, no in vitro studies on human parathyroid cells have been
      reported to date. In this study, the inhibitory effect of cinacalcet on PTH
      secretion was analyzed in primary cultured parathyroid cells obtained from
      patients. The investigation involved three PHPT and three SHPT patients subjected
      to therapeutic parathyroidectomy. Notably, all SHPT patients were resistant to
      intravenous vitamin D analogue therapy. Removed parathyroid tumors were used for
      immunohistochemistry and parathyroid cell primary culture. Immunohistochemical
      analyses revealed diminished expression of CaR and vitamin D receptor (VDR) in
      all parathyroid tumors. PTH secretion from cultured parathyroid cells of PHPT and
      SHPT patients was suppressed by extracellular Ca2+ and cinacalcet in a dose
      dependent manner. Rates of suppression of PTH secretion in PHPT and SHPT by
      cinacalcet (1000 nmol/l) were 61% +/- 21% and 61% +/- 19%, respectively.
      Cinacalcet demonstrates significant potency in the suppression of PTH secretion
      in primary cultured human parathyroid cells in vitro, despite reduced levels of
      the target protein, CaR. Data from this in vitro analysis support the clinical
      application of cinacalcet in PHPT and SHPT therapy.

PMID- 16816925
TI  - Decreased activities of daily living and associations with bone loss among aged
      residents in a rural Japanese community: the Miyama Study.
AB  - The present study aimed to clarify frequencies of decreased activities of daily
      living (ADL) and associations with rate of bone loss among inhabitants more than
      60 years old in Miyama, a rural community in Japan. A cohort of 1543 inhabitants
      aged 40-79 years was established according to Miyama resident registrations in
      1989. Men (n = 50) and women (n = 50) from each of two age strata between 60 and
      79 years (N = 200) were selected from this cohort, and bone mineral density (BMD)
      of the lumbar spine and proximal femur was measured using dual-energy X-ray
      absorptiometry in 1990 (initial survey) and again in 1993, 1997, and 2000.
      Difficulties involving ADL were surveyed at every follow-up study. Of the 200
      initial participants, 124 (57 men, 67 women; 62.0%) completed all BMD
      measurements and answered all items about ADL in the follow-up survey. The
      following items were investigated as a general indication of changes to ADL:
      reaching objects on a high shelf or cupboard (reaching); washing and drying the
      body (washing body); washing hair over a washbasin (washing hair); sitting for 1
      h on a hard chair (sitting); raising the torso from a lying position in bed
      (raising); standing continuously for 30 min (standing); taking socks on and off
      the feet (taking socks); bending down from a seated position and picking up a
      small object at the side of the chair (bending); lifting heavy objects (lifting);
      and running 100 m without stopping (running). Among ADL items, the most frequent
      difficulties in men involved running (50.0%), followed by raising (30.6%),
      standing (27.1%), sitting (24.7%), and reaching (16.5%). In women, difficulties
      involved running (67.0%), followed by lifting (36.3%), standing (33.1%), reaching
      (30.8%), and sitting (23.6%). To evaluate relationships between decreased ADL and
      changes in BMD, annual rates of change for BMD at the lumbar spine and femoral
      neck were compared to changes for each ADL item (2 grade decrease; 1 grade
      decrease; or no change). Analysis of covariance (ANCOVA) was then performed on
      decreased ADL and annual bone changes after adjustment for age, concomitant
      disease (previous fractures, gastrectomy, diabetes mellitus, and renal dialysis
      at initial survey). In men, annual rates of change in BMD at the femoral neck
      over 10 years were significantly correlated with decreased abilities in bending
      (P = 0.046; R2 = 0.10). In women, annual rates of change in BMD at the lumbar
      spine over 10 years were significantly correlated with decreased abilities in
      reaching (P = 0.007; R2 = 0.25), and lifting (P = 0.014, R2 = 0.27), and those at
      the femoral neck were significantly correlated with decreased abilities in
      lifting (P = 0.001, R2 = 0.33).

PMID- 16816926
TI  - Effects of ospemifene and raloxifene on biochemical markers of bone turnover in
      postmenopausal women.
AB  - Ospemifene is a novel selective estrogen receptor modulator (SERM) that is
      initially being developed for the treatment of vaginal atrophy in postmenopausal
      women. However, it also shows promise in the prevention and treatment of
      osteoporosis. As a part of a phase II trial, we compared the effects of
      ospemifene and raloxifene on bone turnover in postmenopausal women. The study was
      conducted as a randomized, double-blind study in which 118 healthy postmenopausal
      women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n
      = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the
      urinary outputs of N- and C-terminal cross-linking telopeptides of type I
      collagen (NTX and CTX, respectively). Bone formation was assessed by measuring
      bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type
      I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All
      markers were studied before and at 3 months and 2-4 weeks after cessation of the
      medication. Urine NTX outputs decreased in all study groups, and the only
      statistically significant difference in NTX was observed between raloxifene and
      30 mg ospemifene, which was reduced more in the raloxifene group. The output of
      CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant
      differences between study groups emerged. A significant difference was found
      between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene.
      No other differences in bone formation markers emerged between ospemifene and
      raloxifene. The study confirms the bone-restoring activity of ospemifene, which
      is comparable to that of raloxifene.

PMID- 16816927
TI  - Abnormal expression of Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage with
      Kashin-Beck disease.
AB  - The purpose of the current study was to investigate the abnormal expression of
      Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage from patients with Kashin
      Beck disease (KBD) to understand the pathogenesis of chondronecrosis in KBD.
      Articular cartilage and growth plate cartilage collected were divided into four
      groups: control children (8 samples, 5 cases), KBD children (19 samples, 9
      cases), control adults (8 samples, 6 cases), and KBD adults (16 samples, 15
      cases). The presence of PTHrP, TGF-beta1, bFGF, VEGF, and collagen X in articular
      cartilage and in growth plate cartilage was analyzed by immunohistochemistry.
      Articular cartilage and growth plate were each divided in three zones, and the
      rate of positive cells was counted by light microscope for cytoplasmic and
      pericellular staining. Results showed that (1) in KBD children, Col X expression
      was lower in the deep zone of growth plate cartilage than in normal children; in
      articular cartilage of KBD adults, however, collagen X expression was higher in
      the middle zone compared to the controls; (2) staining for bFGF, PTHrP, TGF
      beta1, and VEGF in KBD adult patients was prominent in the chondrocyte clusters
      and the eroded surface of articular cartilage, and the percentage of chondrocyte
      staining was significantly higher than in control samples (t = 3.64-10.34, df =
      12 for children and 19 for adults, P = 0.002-0.0001); and (3) the enhanced PTHrP,
      TGF-beta1, and VEGF staining in the deep and middle zone of KBD articular
      cartilage correlated with the high incidence of chondronecrosis in the middle
      zone (48.5% +/- 10.2%) and deep zone (70.6% +/- 27.0%) of adult KBD cartilage. In
      conclusion, Col X expression was reduced in areas of chondrocyte necrosis in the
      deep zone of KBD articular cartilage, indicating changes in terminal chondrocyte
      differentiation. PTHrP, TGF-beta1, and VEGF expression was significantly altered
      and indicated degenerative changes in KBD cartilage, which initially resemble
      those occurring in osteoarthritis, but lead eventually to chondronecrosis, an
      event not observed in osteoarthritis.

PMID- 16816928
TI  - Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone
      turnover in Danish girls.
AB  - Peak bone mass is a major determinant of osteoporosis risk in later life. It is
      under strong genetic control; however, little is known about the identity of the
      genes involved. In the present study, we investigated the relationship between
      polymorphisms in the genes encoding the vitamin D receptor (VDR) (FokI, TaqI) and
      estrogen receptor-alpha (ERalpha) (PvuII, XbaI), and bone mineral density (BMD),
      bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged
      11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum
      osteocalcin, 25(OH)D, and parathyroid hormone (PTH) were measured by ELISA assays
      and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium,
      and Tanner stage were assessed by questionnaire. In general, there were no
      significant differences in anthropometrical variables, physical activity, dietary
      calcium, serum 25(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine
      or whole body (adjusted for body and bone size and pubertal status) were not
      associated with VDR or ERalpha genotypes or the combination of these genotypes.
      This lack of association remained even after adjustment for dietary and
      environmental factors. VDR genotypes had no effect on bone turnover markers. XX
      and PP ERalpha genotypes were associated (P < 0.05) with reduced levels of
      urinary pyridinium cross-links, whereas serum osteocalcin was similar among
      genotypes. These findings suggest that the rate of bone resorption was influenced
      by ERalpha genotypes, even though these biochemical differences were not evident
      in bone mass indices.

PMID- 16816929
TI  - Linkage exclusion mapping with bone size in 79 Caucasian pedigrees.
AB  - Bone size is an important risk factor of osteoporotic fractures and has strong
      genetic determination. However, genetic studies on bone size variation are
      relatively rare. In the present study, we conducted a linkage exclusion mapping
      for bone size variation on chromosomes 1, 4, 6, and 17 in 79 Caucasian pedigrees.
      For hip bone size variation, several genomic regions were excluded at effect
      sizes of 10% or greater, including regions of 61-77cM at 1p35-p34, 43-59cM at
      4p15-p13, 1-59cM at 6p25-p21, 82-88cM at 17q23-q24, and 113-114cM at 17q25. For
      spine bone size, at effect sizes of 10% or greater, we excluded regions of 115
      122cM at 1p31-p22, 136-141cM at 1p21, 207-260cM at 1q31-q42, 20-89cM at 4p16-q21,
      11-21cM at 6p24-p23, and 1-6cM at 17p13. These results suggested that a number of
      candidate genes located in the excluded regions, such as the growth hormone (GH)
      gene, tumor necrosis factor-alpha (TNF-alpha) gene, and bone morphogenetic
      protein-3 (BMP3) gene, are unlikely to have a substantial effect on bone size
      variation in this Caucasian population.

PMID- 16816930
TI  - Prevalence and involvement patterns of radiographic hand osteoarthritis in
      Japanese women: the Hizen-Oshima Study.
AB  - The prevalence and pattern of joint involvement in radiographic hand
      osteoarthritis (OA) have been reported in Western populations, but similar data
      are lacking for Japanese. We examined this issue in 551 Japanese women aged > or
      = 40 years. Radiographs were obtained of both hands and graded according to the
      Kellgren-Lawrence (K-L) criteria. OA was defined as K-L grade 2 or higher. The
      prevalence of radiographic OA in the IP, MCP, and CMC joints was distributed
      similarly in both hands. The most frequent locations of radiographic OA were the
      distal IP joints of the index finger, the IP joint of the thumb, and the distal
      IP joints of the middle finger, in this order. The prevalence of radiographic OA
      in each joint group increased significantly with age, and that in Japanese women
      was lower in the thumb CMC joint and higher in the thumb IP joint compared to
      those in Caucasian women reported previously. The strongest predictor for the
      presence of radiographic OA in a particular joint was the disease status in the
      same joint of the opposite hand (OR = 18.5; 95% CI; 15.2-22.7), followed by the
      joints in the same row of the same hand (OR = 15.5; 95% CI, 11.9-20.1), and then
      by the joints in the same ray of the same hand (OR = 1.3; 95% CI, 1.0-1.6).
      Although the prevalence of hand OA is likely to show site-specific differences
      between Japanese and Caucasian women, our results indicate that both groups show
      similar involvement pattern symmetrically and in the same row of the same hand.

PMID- 16816931
TI  - A case of primary hyperparathyroidism with marked changes in bone mineral density
      and geometry after parathyroidectomy.

PMID- 16816932
TI  - Hoarseness and laryngopharyngeal reflux: a cause and effect relationship or
      coincidence?
AB  - The role of laryngopharyngeal reflux (LPR) on hoarseness is widely assumed and
      accepted. Few articles present objective information on the subject. One of the
      main problems in establishing a relationship is our lack of knowledge of what is
      normal. We compared patients with chronic hoarseness and healthy controls to
      establish three goals: (1) to demonstrate the presence of additional symptoms and
      signs of LPR in patients with hoarseness; (2) to find the prevalence of LPR by
      utilizing 24 h double-probe in patients with hoarseness and compare it with that
      of the control group; (3) to contribute data to establish prevalence of LPR in
      healthy population. Forty-three patients with hoarseness and 20 healthy
      volunteers were enrolled in the study. All the patients in the study group had
      hoarseness of more than 3 months duration. The subjects recieved
      videolaryngoscopic evaluation and 24 h double-probe pH monitoring, and the
      results were compared. In the study group, 27 patients (62.8%) out of 43 had LPR
      episodes, compared to 6 (30%) of 20 healthy volunteers. Mean number of LPR
      episodes recorded by the pharyngeal probe was 7.0 [standard deviation (SD): 8.8]
      in 24 h, and this was significantly higher than that of the healthy controls
      [0.9/24 h (SD: 1.9)] (P = 0.003). Mean number of LPR episodes of the study group
      in upright position was 5.8 (SD: 7,0) and in supine position was 1.2 (SD: 3.3).
      These numbers were also significantly higher from the controls (P = 0.005 and P =
      0.014 respectively). The results of this study show that: (1) most common
      additional symptoms were heartburn and chronic throat clearing and most common
      finding is pachydermia; (2) LPR incidence in patients with chronic hoarseness is
      significantly higher than the LPR incidence in healthy controls; (3) LPR is
      present in healthy people. However, the severity of LPR seems to be the causative
      factor rather than its presence.

PMID- 16816933
TI  - Acoustic rhinometry in nasal provocation test in perennial allergic rhinitis.
AB  - Acoustic rhinometry is one method to evaluate nasal geometry by an acoustic
      reflection technique. The aim of this study was to investigate the changes in
      acoustic rhinometry after nasal provocation in patients with exclusively
      perennial allergic rhinitis. In 19 patients, acoustic rhinometry and active
      anterior rhinomanometry were performed before and after nasal provocation test.
      There was a statistically significant nasal flow reduction measured by active
      anterior rhinomanometry after nasal provocation (p < 0.05) and a median symptom
      score of four points, both indicating a positive response to nasal provocation.
      On the other hand, there was no statistically significant change in the values of
      acoustic rhinometry after nasal provocation (p > 0.05). In patients with
      exclusively perennial allergic rhinitis, acoustic rhinometry does not seem to
      significantly change after nasal provocation. In contrast, active anterior
      rhinomanometry values decreased significantly after nasal provocation. The
      presented results indicate that acoustic rhinometry does not seem to be a
      diagnostic method superior to active anterior rhinomanometry in this context.

PMID- 16816934
TI  - Clinical investigation on hypotensive patients with vertigo.
AB  - The aim of this study was to investigate the characteristic of hypotensive
      patients with vertigo. Twenty hypotensive patients with rotatory vertigo, 15
      hypotensive subjects without vertigo, and 15 mitral valve prolapse subjects
      without vertigo underwent a battery of tests including audiometry,
      electronystagmography (ENG), and vestibular evoked myogenic potential (VEMP)
      test. The abnormal rates in terms of audiometry, eye tracking, optokinetic
      nystagmus, visual suppression, and caloric tests were 15, 35, 35, 10, and 42% for
      the first group; 13, 20, 33, 0, and 0% for the second group; and 7, 13, 60, 0,
      and 3% for the third group, respectively. Comparison of the first group with the
      other two control groups revealed that significant difference existed only in the
      abnormality of caloric responses. Fifteen (75%) of 20 hypotensive patients with
      vertigo having abnormal ENG results, asymmetric caloric responses, or delayed
      VEMPs were attributed to vertigo of central origin, possibly from ischemic
      disorder. In contrast, five patients (25%) had neither central signs in ENG nor
      abnormal VEMPs, but showing bilateral normal or hyperactive caloric responses
      were classified as autonomic dysfunction. After 3 months of medication, all
      patients with autonomic dysfunction had their vertigo and autonomic symptoms
      subsided, whereas 27% of the patients with ischemic disorder had vertigo
      persisted, showing a significant difference. In conclusion, hypotensive patients
      with vertigo could be due to either direct autonomic dysfunction or ischemic
      disorder mediated by autonomic deficits.

PMID- 16816935
TI  - Extraskeletal myxoid chondrosarcoma of the nasal cavity.
AB  - Extraskeletal myxoid chondrosarcoma presenting in the head and neck is extremely
      rare. Histologic diagnosis is difficult and close co-operation among clinician,
      radiologist and pathologist is recommended. The tumour has a better prognosis
      than myxoid chondrosarcoma of the bone but surgical resection may be difficult
      due to its gelatinous nature. We present a case of extraskeletal myxoid
      chondrosarcoma originating in the left nasal cavity of a 35-year-old woman.

PMID- 16816936
TI  - Post-tonsillectomy hematoma of the mouth floor.
AB  - Tonsillectomy is one of the most common operations performed by
      otolaryngologists. Sore throat, otalgia, fever, dehydration, uvular edema, and
      tonsillar hemorrhage are common complications. Hematoma of the mouth floor, an
      unusual complication, was reported. A 21-year-old man presented with a soft, dark
      red swelling of the mouth floor three days after undergoing tonsillectomy. The
      hematoma of the mouth floor subsided spontaneously 2 weeks later. The
      complication in this case was most likely caused by the blood vessel insult,
      which resulted from suspension of the mouth with tongue retraction during
      surgery. This procedure should be done carefully to prevent this complication.
      Hematoma of the mouth floor can cause airway obstruction, and if present, health
      providers should be alert to the possibility of airway compromise.

PMID- 16816937
TI  - Orbital tuberculosis - an interesting case report.
AB  - Orbital tuberculosis is a relatively uncommon disease. A 17-year-old male
      presented with an intraorbital lesion suggestive of orbital pseudotumor. Initial
      clinical response to oral corticosteroid therapy was followed by development of a
      mass lesion in the left orbit, which led to the formation of a discharging sinus
      in relation to the orbit and simultaneous cervical lymphadenitis. Diagnosis of
      tuberculosis was confirmed and patient responded to four drug antitubercular
      therapy. The patient had an unusual presentation and the disease course was
      altered by corticosteroid therapy. This case highlights the need for keeping a
      high index of suspicion for tuberculosis, especially in patients on
      immunosuppressive therapy.

PMID- 16816938
TI  - Cell death in development: shaping the embryo.
AB  - Cell death in animals is normally classified as type I (apoptotic), type II
      (autophagic) or necrotic. Of the biologically controlled types of death, in most
      embryos apoptosis is the most common, although in metamorphosis and in cells with
      massive cytoplasm type II is often seen, and intermediate forms are seen. For
      vertebrate embryos other than mammals, apoptosis is not seen prior to
      gastrulation but thereafter is used to sculpt the organs of the embryo, while
      overproduction of cells with subsequent death of excess cells is a common means
      of generating high specificity with low information cost. In zebrafish at least,
      the inability of embryos prior to the maternal-zygotic transition to undergo
      apoptosis appears to derive from the inability of the cells to resist lysis once
      apoptosis begins, rather than any inhibition of apoptosis. In mammalian embryos,
      apoptosis is seen during cavitation. Thereafter, as in other embryos, cell death
      plays a major role in shaping and sculpting the embryo. In those situations that
      have been carefully studied, cell death is under tight genetic control (including
      regulation of gene products whose function in cell death is not yet known, such
      as cdk5), with activation of apoptosis sometimes regulated by local environmental
      variables.

PMID- 16816940
TI  - Direct molecular haplotyping of multiple polymorphisms within exon 4 of the human
      catechol-O-methyltransferase gene by liquid chromatography-electrospray
      ionization time-of-flight mass spectrometry.
AB  - The applicability of ion-pair reversed-phase high-performance liquid
      chromatography hyphenated to electrospray ionization time-of-flight mass
      spectrometry (ICEMS) for the haplotyping of five SNPs (rs769223, rs4818,
      rs4986871, rs8192488, rs4680) located within exon 4 of the human catechol-O
      methyltransferase (COMT, EC 2.1.1.6) gene is demonstrated. Two differently sized
      products of polymerase chain reaction--a 71-bp amplicon partially covering the
      sequence of a 124-bp amplicon--were used to determine unequivocally the allelic
      states of the single nucleotide polymorphisms linked on both chromosomes. The two
      amplicons were co-loaded onto the chromatographic column and simultaneously
      analyzed within a single gradient run. Using the described strategy, 101
      individuals representing an Austrian population sample were typed. The obtained
      haplotype frequencies will serve as reference values in future association
      studies to examine the impact of the COMT gene on neuropsychiatric disorders.
      Additionally, two newly discovered polymorphic sites within the sequence of the
      COMT gene are described (a synonymous C>T mutation at the third position of the
      amino acid codon 99 in the soluble COMT protein or 149 in the membrane-bound COMT
      protein; a non-synonymous G>A substitution at the second position of the amino
      acid codon 95 in the soluble COMT protein or 145 in the membrane-bound-COMT
      protein).

PMID- 16816939
TI  - The splenic marginal zone in humans and rodents: an enigmatic compartment and its
      inhabitants.
AB  - The role of the spleen in B memory cell development and maintenance is attracting
      increased attention. Studies in mice and rats have indicated that memory
      functions are associated with large B cells residing in the marginal zone (MZ) of
      the spleen. Although the cellular composition of the MZ is relatively well known
      in these species, controversies exist about the function of MZ B cells, their
      dependence on the presence of the spleen and the stage at which their development
      branches from that of recirculating follicular B cells. Additional confusion has
      arisen with respect to MZ B cells in humans, because the microscopic anatomy of
      the human splenic MZ differs decisively from that of rodents. Several recent
      publications indicate that the functional and migratory properties of human MZ B
      cells may be species-specific. The hypothesis derived from these publications and
      from our immunohistological observations implies that at least a major number of
      human splenic CD27(+) MZ B cells are migratory. Phenotypic data suggest a
      recirculation pathway between the spleen and mucosal tissues in humans.

PMID- 16816941
TI  - FT-midIR determination of fatty acid profiles, including trans fatty acids, in
      bakery products after focused microwave-assisted Soxhlet extraction.
AB  - A study of the feasibility of Fourier transform medium infrared spectroscopy (FT
      midIR) for analytical determination of fatty acid profiles, including trans fatty
      acids, is presented. The training and validation sets-75% (102 samples) and 25%
      (36 samples) of the samples once the spectral outliers have been removed-to
      develop FT-midIR general equations, were built with samples from 140 commercial
      and home-made bakery products. The concentration of the analytes in the samples
      used for this study is within the typical range found in these kinds of products.
      Both sets were independent; thus, the validation set was only used for testing
      the equations. The criterion used for the selection of the validation set was
      samples with the highest number of neighbours and the most separation between
      them (H<0.6). Partial least squares regression and cross validation were used for
      multivariate calibration. The FT-midIR method does not require post-extraction
      manipulation and gives information about the fatty acid profile in two min. The
      14:0, 16:0, 18:0, 18:1 and 18:2 fatty acids can be determined with excellent
      precision and other fatty acids with good precision according to the Shenk
      criteria, R (2)>/=0.90, SEP=1-1.5 SEL and R (2)=0.70-0.89, SEP=2-3 SEL,
      respectively. The results obtained with the proposed method were compared with
      those provided by the conventional method based on GC-MS. At 95% significance
      level, the differences between the values obtained for the different fatty acids
      were within the experimental error.

PMID- 16816942
TI  - Rosetted glioneuronal tumour of the spine: clinical, histological and cytogenetic
      data.

PMID- 16816943
TI  - GABAergic modulation of diffuse noxious inhibitory controls (DNIC): a test by use
      of lorazepam.
AB  - Diffuse noxious inhibitory controls (DNIC) are an important supra-spinal
      mechanism of pain inhibition. Neurotransmitters and modulators involved in DNIC
      are serotonin and endogenous opioids. The influence of substances binding to the
      GABA(A) receptor complex, which has been suggested to play an important role in
      descending pain inhibition on DNIC has not yet been investigated. The aim of the
      present study was to find out whether the inhibitory action of DNIC might also be
      mediated by GABAergic mechanisms. Therefore, DNIC modulation via GABAergic
      mechanisms was studied in a double blind, placebo-controlled crossover design by
      oral application of 0.02 mg/kg(body weight )lorazepam in 20 healthy subjects.
      DNIC inhibition was induced by heterotopically administered tonic heat. The
      inhibitory effect was assessed by use of a multiple staircase method, measuring
      electrocutaneous detection, and pain thresholds in parallel. Concurrent tonic
      heat stimuli, at both painful and non-painful levels, significantly increased the
      electrical pain threshold whereas the electrical detection threshold was not
      affected. This pain-specific inhibitory effect did not differ significantly
      between sessions with lorazepam and placebo. Accordingly, lorazepam did not
      modify the inhibitory action of DNIC although lorazepam generally increased heat
      pain threshold. The results of the present study provided no evidence for DNIC
      being mediated by activation of the GABA(A) receptor complex.

PMID- 16816944
TI  - Overlapping visual response latency distributions in visual cortices and LP
      pulvinar complex of the cat.
AB  - The visual system of the cat is considered to be organized in both a serial and
      parallel manner. Studies of visual onset latencies generally suggest that
      parallel processing occurs throughout the dorsal stream. These studies are at
      odds with the proposed hierarchies of visual areas based on termination patterns
      of cortico-cortical projections. In previous studies, a variety of stimuli have
      been used to compute latencies, and this is problematic as latencies are known to
      depend on stimulus parameters. This could explain the discrepancy between latency
      and neuroanatomical based studies. Therefore, the first aim of the present study
      was to determine whether latencies increased along the hierarchy of visual areas
      when the same stimuli are used. In addition, the effect of stimulus complexity
      was assessed. Visual onset latencies were calculated for area 17, PMLS, AMLS, and
      AEV neurons. Latencies were also computed from neurons in the lateral posterior
      (LP)-pulvinar complex given the importance of this extrageniculate complex in
      cortical intercommunication. Latency distributions from all regions overlapped
      substantially, and no significant difference was present, regardless of the type
      of stimulus used. The onset latencies in the LP-pulvinar complex were comparable
      to those seen in cortical areas. The data suggest that the initial processing of
      information in the visual system is parallel, despite the presence of a
      neuroanatomical hierarchy. Simultaneous response onsets among cortical areas and
      the LP-pulvinar suggest that the latter is more than a simple relay station for
      information headed to cortex. The data are consistent with proposals of the LP
      pulvinar as a center for the integration and distribution of information from/to
      multiple cortical areas.

PMID- 16816945
TI  - The vertebral endplate: disc degeneration, disc regeneration.
AB  - The vertebral endplates are critical for maintaining disc function yet like other
      components of the disc are vulnerable to degeneration. This paper provides an
      overview of the development and normal function of the endplates as well as an
      impression of what happens when they undergo progressive degeneration. Recent
      research suggests that the degenerative process can be retarded or reversed.

PMID- 16816946
TI  - Cost-effectiveness of the Danish smoking cessation interventions: subgroup
      analysis based on the Danish Smoking Cessation Database.
AB  - The cost-effectiveness of smoking cessation interventions is well documented.
      However, most studies are based on randomized controlled trials (RCTs) and
      provide little information on the differences between subgroups. This study
      assessed the relative cost-effectiveness of smoking cessation interventions
      offered to various subgroups of smokers, based on real-life data. Regression
      analyses provided information on the factors determining abstinence and costs and
      led to the formation of relevant subgroups of smokers. Probabilistic Markov
      modeling was then used to estimate the relative cost-effectiveness of smoking
      cessation interventions for the entire database population and for the subgroups
      compared to a no-intervention case. The ICER for the base case population was
      estimated at 1,358 euro. This is consistent with results from the existing
      literature. Group simulations showed lower ICERs for men, hospitals, and light
      smokers and falling ICERs with increasing age. Despite differences in the cost
      effectiveness ratios between subgroups our results do not justify any kind of
      subgroup differentiation in a smoking prevention policy.

PMID- 16816947
TI  - The efficacy of autologous platelet gel in pain control and blood loss in total
      knee arthroplasty. An analysis of the haemoglobin, narcotic requirement and range
      of motion.
AB  - Biological materials used to assist in haemostasis following total knee
      arthroplasty have been the subject of much recent research. Autologous platelet
      gel is a substance that is derived from platelet-rich plasma extracted from the
      patient's blood and centrifuged perioperatively, and is applied to exposed
      tissues, synovium and the lining of the wound at closure. Concentrating and
      applying these factors directly to the wound at the end of a total knee
      arthroplasty procedure may lead to more complete haemostasis, a reduction in
      perioperative blood loss, accelerated tissue repair and decreased postoperative
      pain. In this study, 98 unilateral total knee arthroplasties were evaluated
      retrospectively, 61 of which involved the intaroperative use of platelet gel, and
      37 of which served as control subjects. Outcomes analysed were postoperative
      haemoglobin changes, intravenous and oral narcotic requirements, range of motion
      on discharge and total days in hospital. Patients receiving platelet gel during
      surgery had less postoperative blood loss as measured by differences in the
      preoperative and postoperative haemoglobin on day 3 (2.7 vs. 3.2 g/dl; P=0.026).
      The narcotic requirement was less in the platelet gel group for both intravenous
      (17.0 vs. 36.3 mg/day; P=0.024) and oral (1.84 vs. 2.75 tabs/day; P=0.063)
      medication. This group also achieved a higher range of motion prior to discharge
      (78.2 vs. 71.9; P=0.052) and were discharged an average of 1 day earlier than
      their control counterparts. Though further prospective trials are necessary, this
      study indicates that the application of autologous platelet gel may lead to
      improved haemostasis, better pain control and a shortened hospital stay.

PMID- 16816948
TI  - Pol5p, a novel binding partner to Cdc10p in fission yeast involved in rRNA
      production.
AB  - Cdc10p is a major component of the cell cycle transcription factor complex MBF
      that controls G1-S phase specific gene expression in the fission yeast
      Schizosaccharomyces pombe. Here, we describe the identification of a new binding
      partner to Cdc10p and Pol5p. Pol5p was discovered through a 2-hybrid screen, with
      the direct interaction confirmed by in vitro "pull-down" experiments with
      bacterially expressed proteins. Pol5p appears to have no role in cell cycle gene
      expression, but is instead required for rRNA production. Pol5p is an essential
      gene, expressed constitutively throughout both the mitotic and meiotic life
      cycles, and localises to the nucleus. Over-expressing Pol5p has no phenotype, but
      reducing levels of Pol5p inhibits rRNA production. Pol5p is shown to bind to rDNA
      promoter fragments. Potentially, we have identified a mechanism by which Cdc10p
      controls rDNA gene expression, therefore linking the cell cycle with cellular
      growth.

PMID- 16816949
TI  - Both conserved and non-conserved regions of Spo11 are essential for meiotic
      recombination initiation in yeast.
AB  - DNA double-strand breaks (DSBs) are the initiators of most meiotic recombination
      events. In Saccharomyces cerevisiae, at least ten genes are necessary for meiotic
      DSB formation. However, the molecular roles of these proteins are not clearly
      understood. The meiosis-specific Spo11 protein, which shows sequence similarity
      with a subunit of an archaeal topoisomerase, is believed to catalyze the meiotic
      DSB formation. Spo11 is also required for induction of meiotic DSBs at long
      inverted repeats and at large trinucleotide repeat tracts. Here we report the
      isolation and characterization of temperature-sensitive spo11-mutant alleles to
      better understand how Spo11 functions, and how meiotic DSBs are generated at
      various recombination hotspots. Analysis of mutation sites of isolated spo11
      mutant alleles indicated that both N-terminal and C-terminal non-conserved
      residues of Spo11 are essential for the protein's function, possibly for
      interaction with other meiotic DSB enzymes. Several of the mutation sites within
      the conserved region are predicted to lie on the surface of the protein,
      suggesting that this region is required for activation of the meiotic initiation
      complex via protein-protein interaction. In addition to the conditional mutants,
      we isolated partially recombination-defective mutants; analysis of one of these
      mutants indicated that Ski8, as observed previously, interacts with Spo11 via the
      latter's C-terminal residues.

PMID- 16816950
TI  - Vildagliptin therapy reduces postprandial intestinal triglyceride-rich
      lipoprotein particles in patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: We assessed the effects of vildagliptin, a novel dipeptidyl
      peptidase IV inhibitor, on postprandial lipid and lipoprotein metabolism in
      patients with type 2 diabetes. SUBJECTS, MATERIALS AND METHODS: This was a single
      centre, randomised, double-blind study in drug-naive patients with type 2
      diabetes. Patients received vildagliptin (50 mg twice daily, n=15) or placebo
      (n=16) for 4 weeks. Triglyceride, cholesterol, lipoprotein, glucose, insulin,
      glucagon and glucagon-like peptide-1 (GLP-1) responses to a fat-rich mixed meal
      were determined for 8 h postprandially before and after 4 weeks of treatment.
      RESULTS: Relative to placebo, 4 weeks of treatment with vildagliptin decreased
      the AUC(0-8h) for total trigyceride by 22+/-11% (p=0.037), the incremental AUC(0
      8h) (IAUC(0-8h)) for total triglyceride by 85+/-47% (p=0.065), the AUC(0-8h) for
      chylomicron triglyceride by 65+/-19% (p=0.001) and the IAUC(0-8h) for chylomicron
      triglyceride by 91+/-28% (p=0.002). This was associated with a decrease in
      chylomicron apolipoprotein B-48 (AUC(0-8h), -1.0+/-0.5 mg l(-1) h, p=0.037) and
      chylomicron cholesterol (AUC(0-8h), -0.14+/-0.07 mmol l(-1) h, p=0.046).
      Consistent with previous studies, 4 weeks of treatment with vildagliptin also
      increased intact GLP-1, suppressed inappropriate glucagon secretion, decreased
      fasting and postprandial glucose, and decreased HbA(1c) from a baseline of 6.7%
      (change, -0.4+/-0.1%, p<0.001), all relative to placebo.
      CONCLUSIONS/INTERPRETATION: Treatment with vildagliptin for 4 weeks improves
      postprandial plasma triglyceride and apolipoprotein B-48-containing triglyceride
      rich lipoprotein particle metabolism after a fat-rich meal. The mechanisms
      underlying the effects of this dipeptidyl peptidase IV inhibitor on postprandial
      lipid metabolism remain to be explored.

PMID- 16816951
TI  - Antibiotic treatment partially protects against type 1 diabetes in the Bio
      Breeding diabetes-prone rat. Is the gut flora involved in the development of type
      1 diabetes?
AB  - AIMS/HYPOTHESIS: Accumulating data suggest that the gut immune system plays a
      role in the development of type 1 diabetes. The intestinal flora is essential for
      the development of the (gut) immune system and the establishment of tolerance. It
      has been reported that oral administration of food and bacterial antigens early
      in life suppresses later development of diabetes in the Bio-Breeding diabetes
      prone (BB-DP) rat. This study was designed to investigate the possible
      relationship between the development of diabetes and the composition of
      intestinal flora. MATERIALS AND METHODS: The intestinal flora of BB-DP rats, a
      rat model for type 1 diabetes, was characterised long before the clinical onset
      of diabetes by fluorescent in situ hybridisation. In a separate experiment, BB-DP
      rats were treated with antibiotics and the effect on diabetes incidence and level
      of insulitis was analysed. RESULTS: We observed a difference in bacterial
      composition between rats that eventually did and those that did not develop
      diabetes. This difference was detectable long before clinical onset of the
      disease. Rats that did not develop diabetes at a later age displayed a lower
      amount of Bacteroides sp. Modulation of the intestinal flora through antibiotic
      treatment decreased the incidence and delayed the onset of diabetes. A
      combination of antibiotic treatment and a protective hydrolysed casein diet
      completely prevented diabetes in the BB-DP rat. CONCLUSIONS/INTERPRETATION: Our
      data suggest that the intestinal flora is involved in the development of type 1
      diabetes. Factors influencing composition of the intestinal flora could be a
      target for therapeutic intervention.

PMID- 16816952
TI  - Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control
      of patients with permanent neonatal diabetes mellitus due to activating mutations
      of the KCNJ11 (KIR6.2) gene.

PMID- 16816953
TI  - Plasma concentrations of vascular endothelial growth factor are associated with
      peripheral oedema in patients treated with thiazolidinedione.

PMID- 16816954
TI  - [Therapy of atopic dermatitis].
AB  - Atopic eczema is one of the most common diseases in dermatology. Patients suffer
      from both the chronic relapsing skin disease and the associated emotional stress.
      Itching and visible lesions on the face and hands are the most unpleasant
      features for many often young patients, seriously reducing their quality of life.
      New therapeutic approaches have changed the management of atopic eczema in recent
      years. Relatively potent new drugs with fewer side effects than corticosteroids
      help to control the disease. This review focuses on the basic principles of
      modern atopic eczema treatment, emphasizing basic emollient therapy and topical
      therapy with calcineurin inhibitors.

PMID- 16816955
TI  - Prospective analysis of uncomplicated bone bruises in the pediatric knee.
AB  - To determine the incidence of uncomplicated knee bone contusions in pediatric
      patients. MRI studies were obtained using either high-field (1.5 T) or mid-field
      strength magnets (0.2-0.3 T), identifying 48 pediatric patients suitable for
      study. Contusion location, size, and any ligamentous or meniscal injuries were
      recorded. Exclusionary criteria did not include plain film findings, the interval
      between injury to imaging, or history of patellar dislocation [Fulkerson (2002)
      30:447-456]. Uncomplicated bone bruises were those occurring in the absence of
      other internal derangements of the knee, such as meniscal and ligament tears.
      Consensus imaging findings by two reviewing radiologists revealed a 25% incidence
      of uncomplicated bruises (12/48 patients). These bone bruises involved the
      lateral and medial knee compartments 56 and 44% of the time, respectively.
      Bruises of the lateral compartment were larger (2.4 cm) than those found in the
      medial compartment (1.8 cm). Given the high incidence of symptomatic but
      uncomplicated contusions identified in this study of a pediatric population, we
      suggest appropriate joint rest and follow-up without other intervention as a
      primary course of treatment.

PMID- 16816956
TI  - Splenic rupture after diagnostic colonoscopy: a case report.
AB  - Colonoscopy is a commonly used diagnostic and therapeutic procedure. Splenic
      injury or rupture after this procedure is rare. We report a case of splenic
      rupture and hematoma in a middle-aged man who presented with symptoms of worsened
      anemia after diagnostic colonoscopy.

PMID- 16816957
TI  - A case of hepatocellular carcinoma who admitted with Raynaud's phenomenon.
AB  - Hepatocellular carcinoma (HCC) may be present in one of the several ways. The
      classical presentation is with right upper quadrant abdominal pain, abdominal
      swelling and weight loss. HCC may also be associated with several paraneoplastic
      manifestations. The mechanisms of these manifestations are not well known. The
      association of digital ischemia and malignancy was reported as early as 1884 and
      1891. We report a case of HCC associated with Raynaund's phenomenon.

PMID- 16816959
TI  - Amoeboid form of Blastocystis hominis - a detailed ultrastructural insight.
AB  - The amoeboid form of Blastocystis hominis has been reported infrequently, and its
      morphological descriptions have yielded conflicting and confusing reports. In the
      present study, we used the amoeboid forms seen predominantly in symptomatic
      patients infected with Blastocystis to provide detailed descriptions on the fine
      surface structure and intracellular morphology. Scanning electron microscopy
      revealed the irregular shape of the amoeboid form, with an intercalated fibrillar
      structure and a highly convoluted surface with deep indentations and projected
      pseudopodia. Transmission electron microscopy showed the existence of two types
      of amoeboid forms of B. hominis in in vitro culture, one with a large central
      vacuole containing tiny electron-dense particles while the other contains
      multiple small vacuoles in the cytoplasm. A surface coat with varying thickness
      surrounded the amoeboid form, which also showed prominent, extended pseudopodia
      of varying shape. Irregularly shaped mitochondrion-like organelles with prominent
      cristae, lipid inclusions, and multiple vacuoles were frequently seen in close
      proximity with the pseudopodia. The characteristic nucleus with a crescentic band
      of electron-dense chromatin material was also seen.

PMID- 16816958
TI  - Reduction of tick infections with Anaplasma marginale and A. phagocytophilum by
      targeting the tick protective antigen subolesin.
AB  - Subolesin was recently shown by both gene silencing and immunization with the
      recombinant protein to protect against tick infestations, and to cause reduced
      tick survival and degeneration of gut and salivary gland tissues. In this
      research, we extended these studies by testing whether targeting subolesin by
      RNAi or vaccination interfered with the ability of ticks to become infected with
      two tick-borne pathogens, Anaplasma marginale which causes bovine anaplasmosis
      and Anaplasma phagocytophilum, the causative agent of human granulocytin
      anaplasmosis. For the A. marginale studies, Dermacentor variabilis males were
      injected with subolesin dsRNA or saline and then were allowed to feed on cattle
      with ascending rickettsemias, while for the A. phagocytophilum studies, mice were
      immunized with the recombinant subolesin protein, infected with the pathogen and
      then infested with larval Ixodes scapularis. Tick infections were determined by
      quantitative polymerase chain reaction of gut and salivary gland tissues. In both
      experimental approaches, tick infections were significantly reduced. These
      results suggest that subolesin appears to be a candidate vaccine antigen that may
      contribute to control of multiple tick species and the reduction of tick-borne
      pathogens.

PMID- 16816960
TI  - A simplified method of antibiotic lock therapy for Broviac-Hickman catheters
      using a CLC 2000 connector device.
AB  - INTRODUCTION: We report a simplified method of performing antibiotic lock therapy
      (ALT) based on a disposable central venous catheter (CVC) hub device, CLC 2000,
      enabling an open-ended CVC to be flushed with normal saline solution without
      heparin. METHODS: ALT was administered through a CLC 2000 connector for recurrent
      CVC-bloodstream infections (BSI) by the same organism in four patients and for
      CVC colonization in five patients. RESULTS: The antibiotic concentration obtained
      in the lumen of the CVC with ALT was 2,500-fold higher than the minimum
      inhibiting concentration of targeted bacteria for patients treated with
      vancomycin, 2,500-80,000-fold higher for patients treated with teicoplanin, and
      10,000-fold higher for the patient treated with amikacin. All CVC-BSIs treated
      with ALT resulted in complete clinical and microbiological responses. No case of
      malfunction in withdrawing or flushing the CVC and no precipitation during the
      administration of the antibiotic solution was observed. No recurrence of CVC-BSI
      or CVC colonization by the same organism was diagnosed during subsequent follow
      up, despite the fact that all patients had further periods of severe neutropenia.
      At the last follow-up, three CVCs had been removed for other infections (fever of
      unknown origin in two; fungemia in one), four CVCs had been removed at the end of
      therapy, and one CVC is still in situ 20 months after ALT. CONCLUSIONS: In
      conclusion, a course of ALT is feasible in cancer patients with infected but much
      needed CVCs before resorting to removal. The use of the CLC 2000 connector device
      simplifies the procedure for preparation and administration of ALT without
      compromising its efficacy.

PMID- 16816961
TI  - The effects of age and emotional acceptance on distress among breast cancer
      patients.
AB  - OBJECTIVES: This study examined whether emotional acceptance moderates the
      relationship between age and distress among breast cancer patients near the end
      of the first year after diagnosis. MATERIALS AND METHOD: The Emotional acceptance
      scale and the Profile of Mood States scale were completed by 79 women with Stage
      II or III breast cancer. RESULTS: Results showed that younger women reported
      greater distress than older women. Those who were less accepting of their
      emotions also reported greater distress than those who were more accepting,
      regardless of age. DISCUSSION: These results suggest that emotional acceptance
      may be beneficial for both younger and older women facing breast cancer.
      Additional implications of these findings are discussed.

PMID- 16816962
TI  - [Total hip arthroplasty in cerebral palsy].
AB  - BACKGROUND: The treatment of painful osteoarthritis of the hip in cerebral palsy
      requires a therapy concept that considers the pathoanatomical features and adapts
      the treatment to the individual physical and mental abilities. Femoral head
      resection has been proven be effective in severely dislocated hip joints in
      completely immobilized patients, whereas no satisfactory outcome is achieved in
      those patients with sufficient walking ability and moderate expression of
      spasticity. RESULTS: The following study investigates the results of total hip
      replacement (THR) in patients with tetraspastic cerebral palsy. Between 1992 and
      2004, 19 total hip arthroplasties were performed in 175 patients with an average
      follow-up of 4,6 years. In all patients the walking ability improved
      significantly; 84% of the patients were pain free. Aseptic loosening of the
      femoral component was registered in one patient. A periprosthetic fracture in
      another patient required the implantation of a modular non-cemented femoral
      component. CONCLUSION: In this study total hip arthroplasty represents an
      important expansion of operative treatment options in secondary osteoarthritis of
      cerebral palsy in selected and cooperative patients. Taking the contradictions
      into consideration (severe athetosis, absence of adequate weight bearing, severe
      pelvic obliquity), THR promises to be an effective alternative to femoral head
      resection with significant pain reduction and improvement of walking abilities.

PMID- 16816963
TI  - Correction of high myopia with different phakic anterior chamber intraocular
      lenses: ICARE angle-supported lens and Verisyse iris-claw lens.
AB  - PURPOSE: To evaluate the efficacy, predictability and safety of implanting two
      models of anterior chamber IOLs for high myopia. Comparison of the refractive
      results between two groups of patients implanted with different IOLs. MATERIALS
      AND METHODS: Forty eyes were implanted with phakic IOLs. The ICARE myopia lens
      was implanted in 20 eyes of 12 patients with preoperative myopia that ranged from
      -21.875 to -10.0. The mean patients' age was 30 years. The Verisyse IOL was
      implanted in 20 eyes of 12 patients with spherical equivalent of the refractive
      error from -21.625 to -10.375D, and the mean patients' age was 32.25 years. The
      dioptric power of the intraocular lens was calculated by considering refraction,
      keratometry, and anterior chamber depth. The follow-up period was 12 months.
      RESULTS: Twelve months after surgery, the mean refractive error (SE) was -0.19D
      (100% of eyes were within +/-1.0D of the target refraction) in the ICARE group,
      and -0.86D (95% of eyes were within +/-1.0D of the target refraction) in the
      Verisyse group. The postoperative refraction remained stable during the entire
      follow-up period. The mean uncorrected visual acuity was 0.7 in the ICARE group,
      and 0.69 in the Verisyse group 1 year postoperatively. There was no loss in
      visual acuity 1 year after surgery in the ICARE implanted eyes, one patient in
      the Verisyse group lost 1 line of BCVA as compared to the preoperative state.
      Mean endothelial cell density loss was 6.12% and 6.79% in the ICARE and Verisyse
      groups, respectively. There were no statistically significant differences
      regarding the analyzed outcome parameters between the two study groups.
      CONCLUSION: The implantation of both anterior chamber phakic intraocular lenses
      to correct high myopia resulted in a stable and predictable refractive outcome.
      Efficacy and safety of surgery for both implanted lens models are very high.

PMID- 16816964
TI  - Characterization of the HMW glutenin subunits from Aegilops searsii and
      identification of a novel variant HMW glutenin subunit.
AB  - High molecular weight (HMW) glutenin subunits are conserved seed storage proteins
      in wheat and related species. Here we describe a more detailed characterization
      of the HMW glutenin subunits from Aegilops searsii, which is diploid and contains
      the S(s) genome related to the S genome of Aegilops speltoides and the A, B and D
      genomes of hexaploid wheat. SDS-PAGE experiments revealed two subunits (one x and
      one y) for each of the nine Ae. searsii accessions analyzed, indicating that the
      HMW glutenin subunit gene locus of Ae. searsii is similar to the Glu-1 locus
      found in wheat in containing both x and y genes. The primary structure of the
      four molecularly cloned subunits (from two Ae. searsii accessions) was highly
      similar to that of the previously reported x and y subunits. However, in one
      accession (IG49077), the last 159 residues of the x subunit (1S(s)x49077), which
      contained the sequence element GHCPTSPQQ, were identical to those of the y
      subunit (1S(s)y49077) from the same accession. Consequently, 1S(s)x49077 contains
      an extra cysteine residue located at the C-terminal part of its repetitive
      domain, which is novel compared to the x-type subunits reported so far. Based on
      this and previous studies, the structure and expression of the Glu-1 locus in Ae.
      searsii is discussed. A hypothesis on the genetic mechanism generating the coding
      sequence for the novel 1S(s)x49077 subunit is presented.

PMID- 16816965
TI  - Dendritic spikes and activity-dependent synaptic plasticity.
AB  - Whereas the regenerative nature of action potential conduction in axons has been
      known since the late 1940s, neuronal dendrites have been considered as passive
      cables transferring incoming synaptic activity to the soma. The relatively recent
      discovery that neuronal dendrites contain active conductances has revolutionized
      our view of information processing in neurons. In many neuronal cell types,
      sodium action potentials initiated at the axon initial segment can back-propagate
      actively into the dendrite thereby serving, for the dendrite, as an indicator of
      the output activity of the neuron. In addition, the dendrites themselves can
      initiate action-potential-like regenerative responses, so-called dendritic
      spikes, that are mediated either by the activation of sodium, calcium, and/or N
      methyl-D-aspartate receptor channels. Here, we review the recent experimental and
      theoretical evidence for a role of regenerative dendritic activity in information
      processing within neurons and, especially, in activity-dependent synaptic
      plasticity.

PMID- 16816966
TI  - Dedifferentiated high-grade osteosarcoma originating from low-grade central
      osteosarcoma of the fibula.
AB  - Low grade central osteosarcoma is a distinct, rare low grade malignant neoplasm
      characterized histologically by a spindle cell proliferation associated with
      trabecular bone formation. This tumor usually carries a good prognosis. However,
      it has the potential to recur, dedifferentiate, and metastasize subsequent to
      surgical treatment. In extremely rare occasions, LGCOS presents with areas of
      dedifferentiation upon initial patient evaluation. In this report we describe one
      such case affecting the fibula of a 39-year-old female, presenting with pain.
      Initial biopsy demonstrated a high-grade osteosarcoma. No areas of LGCOS were
      seen histologically. Following biopsy the patient received 3 months of
      chemotherapy at a different institution. However, the patient continued to
      exhibit symptoms. X-rays indicated a very aggressive tumor in the diaphysis of
      the proximal fibula, MRI revealed soft tissue involvement. The tumor and
      surrounding soft-tissues were excised en bloc at our institution.
      Microscopically, the lesion consisted of high-grade osteosarcoma as well as an
      underlying LGCOS that involved the cortex and medullary cavity of the fibula. The
      two histological components of the tumor were sharply delineated from one
      another. No chemotherapy effect was appreciated histologically or clinically.
      Eight months following the surgery, the patient died from lung metastases. This
      is the third documented case of dedifferentiated LGCOS at initial presentation.
      This case reveals that the low-grade component was also evident on preoperative
      radiographs.

PMID- 16816968
TI  - The ten Hox genes of the millipede Glomeris marginata.
AB  - We have isolated the ten Hox genes from the pill millipede Glomeris marginata
      (Myriapoda:Diplopoda). All ten genes are expressed in characteristic Hox-gene
      like expression patterns. The register of Hox gene expression borders is
      conserved and the expression profiles show that the anterior-most limb-bearing
      segment in arthropods (antennal/cheliceral segment) does not express any Hox
      gene, while the next segment (intercalary/second
      antennal/premandibular/pedipalpal segment) does express Hox genes. The Hox
      expression patterns in this millipede thus support the conclusion that all
      arthropods possess a deuterocerebral segment. We find that there is an apparent
      posterior shift of Hox gene expression domains dorsally relative to their ventral
      patterns, indicating that the decoupling of dorsal and ventral segmentation is
      not restricted to the level of segment polarity genes but apparently includes the
      Hox genes. Although the mechanism for the decoupling of dorsal and ventral
      segmentation remains unsolved, the decoupling must be at a level higher in the
      hierarchy than that of the segment polarity and Hox genes. The expression
      patterns of Ultrabithorax and abdominal-A suggest a correlation between the
      function of these genes and the delayed outgrowth of posterior trunk appendages.
      This delay may be caused by an assumed repressor function of Ultrabithorax, which
      might partially repress the activation of the Distal-less gene. The Glomeris
      fushi tarazu gene is expressed in a Hox-like domain and in the developing central
      nervous system, but not in segmental stripes such as has been reported in another
      myriapod species, the centipede Lithobius. In contrast to the Lithobius fushi
      tarazu gene, there is no indication for a role in segment formation for the
      millipede fushi tarazu gene, suggesting that fushi tarazu first acquired its
      segmentation function in the lineage of the insects.

PMID- 16816970
TI  - A maternal hypomethylation syndrome presenting as transient neonatal diabetes
      mellitus.
AB  - The expression of imprinted genes is mediated by allele-specific epigenetic
      modification of genomic DNA and chromatin, including parent of origin-specific
      DNA methylation. Dysregulation of these genes causes a range of disorders
      affecting pre- and post-natal growth and neurological function. We investigated a
      cohort of 12 patients with transient neonatal diabetes whose disease was caused
      by loss of maternal methylation at the TNDM locus. We found that six of these
      patients showed a spectrum of methylation loss, mosaic with respect to the extent
      of the methylation loss, the tissues affected and the genetic loci involved. Five
      maternally methylated loci were affected, while one maternally methylated and two
      paternally methylated loci were spared. These patients had higher birth weight
      and were more phenotypically diverse than other TNDM patients with different
      aetiologies, presumably reflecting the influence of dysregulation of multiple
      imprinted genes. We propose the existence of a maternal hypomethylation syndrome,
      and therefore suggest that any patient with methylation loss at one maternally
      methylated locus may also manifest methylation loss at other loci, potentially
      complicating or even confounding the clinical presentation.

PMID- 16816971
TI  - [To Prof. Dr. Werner Wenz on the occasion of his 80th birthday].

PMID- 16816969
TI  - The evolution of arthropod heads: reconciling morphological, developmental and
      palaeontological evidence.
AB  - Understanding the head is one of the great challenges in the fields of
      comparative anatomy, developmental biology, and palaeontology of arthropods.
      Numerous conflicting views and interpretations are based on an enormous variety
      of descriptive and experimental approaches. The interpretation of the head
      influences views on phylogenetic relationships within the Arthropoda as well as
      outgroup relationships. Here, we review current hypotheses about head
      segmentation and the nature of head structures from various perspectives, which
      we try to combine to gain a deeper understanding of the arthropod head. Though
      discussion about arthropod heads shows some progress, unquestioned concepts
      (e.g., a presegmental acron) are still a source of bias. Several interpretations
      are no longer tenable based on recent results from comparative molecular
      developmental studies, improved morphological investigations, and new fossils.
      Current data indicate that the anterior arthropod head comprises three elements:
      the protocerebral/ocular region, the deutocerebral/antennal/cheliceral segment,
      and the tritocerebral/pedipalpal/second antennal/intercalary segment. The labrum
      and the mouth are part of the protocerebral/ocular region. Whether the labrum
      derives from a former pair of limbs remains an open question, but a majority of
      data support its broad homology across the Euarthropoda. From the alignment of
      head segments between onychophorans and euarthropods, we develop the concept of
      "primary" and "secondary antennae" in Recent and fossil arthropods, posit that
      "primary antennae" are retained in some fossil euarthropods below the crown group
      level, and propose that Trilobita are stem lineage representatives of the
      Mandibulata.

PMID- 16816972
TI  - Fascaplysin, a selective CDK4 inhibitor, exhibit anti-angiogenic activity in
      vitro and in vivo.
AB  - PURPOSE: This study was to evaluate the correlation of two important strategies,
      namely, cell cycle proliferation arrest and anti-angiogenesis. We chose
      fascaplysin, a marine natural product with selective CDK4 selective inhibition
      activity, to study its potential anti-angiogenesis effects in vivo and in vitro.
      METHODS: Chorioallantoic membrane (CAM) assay was initially used as an in vivo
      approach to evaluate anti-angiogenic activity of fascaplysin. In addition, human
      umbilical vein endothelial cell (HUVEC) line was used to further confirm the anti
      angiogenic activity of fascaplysin in vitro. To explore the mechanism of anti
      angiogenesis, we examined the effect of fascaplysin on vascular endothelial
      growth factor (VEGF) expression and secretion by hepatocarcinoma cells BeL-7402.
      RESULTS: The results of CAM assay suggested fascaplysin inhibited capillary
      plexus formation in a dose-dependent manner and suppressed VEGF in cross section.
      Moreover, the in vitro assay also confirmed that fascaplysin provided selective
      inhibition of endothelial cells proliferation towards tumor cells in low
      concentration. The immunocytochemical staining and ELISA verified fascaplysin
      could inhibit VEGF expression and secretion by BeL-7402. CONCLUSIONS: These
      findings strongly suggest that fascaplysin is a natural angiogenesis inhibitor.

PMID- 16816973
TI  - [Pedunculated conjunctival tumor. Pedunculated conjunctival metastases of a clear
      cell kidney carcinoma].

PMID- 16816974
TI  - [Terminally ill tumor patients in emergency medical care].
AB  - We report about an emergency case of a female patient with terminal carcinoma of
      the ovary. On the basis of this case it becomes evident that palliative care
      questions are also important in emergency medicine. In this situation cooperation
      of the medical disciplines involved appears urgently necessary. This may allow
      the possibility for terminally ill patients to stay at home in the last days of
      life.

PMID- 16816975
TI  - [Coagulation monitoring of lung embolism using thrombelastography. Resuscitation-
      Thrombolysis--Massive haemorrhaging].
AB  - Thrombelastography (TEG) is a bedside method used to determine coagulation
      parameters such as clot formation, stabilization and lysis. This report describes
      a case of cardiopulmonary arrest due to fulminant pulmonary embolism in a 42-year
      old postpartum patient. We discuss the dynamics of coagulation parameters during
      CPR and thrombolysis complicated by bleeding, as assessed by TEG.

PMID- 16816976
TI  - [Comment on the STAR study: Comparison of the efficacy and tolerance of
      solifenacin and tolterodine retard in the treatment of overactive bladder].

PMID- 16816977
TI  - Genetic susceptibility to Parkinson's disease among South and North Indians: I.
      Role of polymorphisms in dopamine receptor and transporter genes and association
      of DRD4 120-bp duplication marker.
AB  - The depletion of dopamine levels in the brain due to degeneration of dopaminergic
      neurons of substantia nigra pars compacta is a hallmark of Parkinson's disease
      (PD). The cumulative contribution of genetic variations in genes from the
      dopaminergic pathway has been widely implicated to confer susceptibility to
      idiopathic PD. We present in this paper an extensive association analysis of a
      total of 20 markers including single nucleotide polymorphism/short tandem
      repeat/variable number tandem repeat/duplication markers from five candidate
      genes (namely, dopamine receptors DRD1, DRD2, DRD3, and DRD4, and dopamine
      transporter) with PD among two independent sample sets. The allelic, genotypic,
      and haplotypic association of these markers with PD was tested in South Indian
      (SI) samples (147 cases, 130 controls) and replicated in a larger North Indian
      (NI) sample set (340 cases, 344 controls). Of the several markers analyzed, 120
      bp duplication marker of DRD4 gene showed promising results with PD in both of
      the sample sets. A significant allelic association in SI [odds ratio, OR (95%
      confidence interval, CI)=0.67 (0.47-0.97) for 120 bp dup; 1.48 (1.03-2.13) for
      120 bp WT] and genotypic association in SI [OR (95% CI)= 0.56 (0.35-0.91) for 120
      bp dup/dup; 1.62 (0.99-2.64) for 120 bp dup/120 bp WT] and in NI [OR (95% CI)=
      1.41 (1.03-1.93) for 120 bp dup/120 bp WT] was observed. This is the first report
      on the association of dopaminergic gene polymorphisms with PD from the Indian sub
      continent.

PMID- 16816979
TI  - Editorial on "Surgical treatment of epilepsy in children".

PMID- 16816978
TI  - Acute necrotizing encephalopathy: combined therapy and favorable outcome in a new
      case.
AB  - BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare disease
      characterized by multiple, symmetrical brain lesions, affecting thalami,
      brainstem tegmentum, and cerebellar medulla; more inconstantly, other structures
      are involved, i.e., internal capsules, posterolateral putamen, and deep
      periventricular white matter. FEATURES: The clinical picture consists of rapidly
      deteriorating acute monophasic encephalopathy preceded by prodromal febrile
      illness; the symptoms include hyperpyrexia, convulsions, recurrent vomiting, and
      coma within 24 h. PROGNOSIS: The outcome is usually poor and approximately 70% of
      the patients die within a few days from the onset of fever. There is no specific
      therapy for ANE but, in some patients, the clinical status improved with steroid
      treatment.

PMID- 16816980
TI  - Symptomatic epilepsy in children with poroencephalic cysts secondary to perinatal
      middle cerebral artery occlusion.
AB  - BACKGROUND: Perinatal cerebral artery occlusion is responsible for ischemic
      cerebral infarction leading to brain cavitation and gliosis; the territory of the
      middle cerebral artery is most frequently involved. The resulting poroencephalic
      cysts are frequently associated with hemiplegia and epilepsy; that can be managed
      medically in most cases, only 6-7% of them being refractory to medical treatment.
      This particular subset of congenitally hemiplegic children will be possible
      candidates for electrophysiological investigation and eventually for resective
      surgery. Whatever the kind of surgical treatment, surgery should be performed as
      soon as possible to optimize functional brain reorganization. CLINICAL MATERIAL:
      Twelve children with poroencephalic cysts and refractory epilepsy were studied
      and operated on at the Divisions of Child Neurology and Pediatric Neurosurgery,
      the Catholic University Medical School, Rome. The hemiparesis ranged from mild to
      moderate; the developmental delay was of mild degree in three cases, moderate in
      four cases and severe in the remaining five. Behavioral disorders were observed
      in patients with mental retardation; two of them also manifested autistic
      features. All the children presented with a severe epileptic syndrome (starting
      almost invariably during the first year of life); six patients presented with a
      West syndrome followed by symptomatic partial epilepsy; the other six presented
      with partial epilepsy, followed in two cases by continuous spike-waves during
      sleep. The electroencephalograph (EEG) recordings disclosed focal unilateral
      interictal epileptiform abnormalities that usually corresponded to the side of
      the cystic lesion; however, paroxysmal activity often spread synchronously over
      the contralateral hemisphere. The selection of candidates for surgical treatment
      was based on neuroimaging and video-EEG monitoring; in particular, we did not use
      invasive intraoperative neurophysiologic techniques. The convergence of
      neuroimaging and neurophysiologic findings guided us in performing a limited
      cortical excision corresponding to the malacic cortex (cyst "membrane"). RESULTS:
      All the patients underwent excision of the cyst wall. Careful attention was paid
      not to enter the body of the lateral ventricle to avoid ventriculo-subarachnoid
      fistulas, eventually responsible for subdural hygroma or cerebrospinal fluid
      leak. There was one surgery-related death secondary to disseminated intravascular
      coagulation, following an otherwise uneventful surgical procedure. An elevated
      systemic blood pressure, secondary to repeated adrenocorticotropic hormone
      therapy, can represent a possible concurrent factor for this event. No major
      complications were recorded among the remaining 11 children. Seizure control was
      excellent in all the 11 survivors in the early postoperative period. Two children
      presented a relapse of seizures, after an initial improvement, respectively 3 and
      4 years after the operation. These two children underwent subsequently a
      functional hemispherectomy. Overall, seizure outcome was excellent in all the
      cases. Seven patients (including the two who underwent functional
      hemispherectomy) are seizure-free (Engel's class Ia), and in one of them
      antiepileptic therapy has been weaned. In the remaining five children, seizures
      are sporadic and definitely improved (Engel's class II). An improvement of
      developmental delay, in particular of cognitive competence, was registered in 8
      out of the 11 patients. Two of the four severely retarded children, who also
      presented behavioral abnormalities, did not show any cognitive improvement,
      whereas some mild improvement of their basal abilities was demonstrated in the
      other two. All the remaining children, even though maintaining a moderate
      retardation, definitely improved their abilities; in particular, one of them
      reached an almost borderline level. The three patients with unchanged
      neurodevelopmental delay presented also persistent seizures. On the other hand,
      two children with persistent seizures presented neurodevelopmental improvement.
      CONCLUSIONS: Simple surgical excision of the cyst "membrane" of epileptogenic
      poroencephalic cysts can represent an excellent means to control epilepsy in
      affected children. However, postoperative seizure persistence and late
      recurrences, although rare, do not allow to exclude that hemispherectomy or
      partial resections (based on electrocorticography findings) might represent the
      good answer at least in some cases.

PMID- 16816981
TI  - Vagal nerve stimulation for refractory epilepsy in children: indications and
      experience at The Hospital for Sick Children.
AB  - OBJECTIVES: The management of intractable epilepsy in children is a challenging
      problem. For those patients who do not respond to antiepileptic drugs and are not
      candidates for epilepsy surgery, vagal nerve stimulation (VNS), can be a viable
      alternative for reducing seizure frequency. We have reviewed the historical and
      clinical background of VNS treatment. We also include our experience at The
      Hospital for Sick Children in children who underwent VNS implantation. METHODS:
      Forty-one children underwent VNS implantation for epilepsy over 6 years. After a
      mean follow-up of 31 months, 15 (38%) patients had a seizure frequency reduction
      of more than 90%. Fifteen (38%) children failed to respond to the VNS treatment.
      The device was removed in five children: in one, due to late infection; the other
      four could not tolerate the side effects of chronic VNS therapy. Two patients
      required reimplantation due to electrode failure. The most common side effects in
      our series were cough and vocal disturbances. CONCLUSIONS: Our results show that
      VNS implantation can be a safe and effective alternative therapy for children
      with drug-resistant epilepsy who are not candidates for epilepsy surgery.

PMID- 16816982
TI  - Is the increase in type III collagen of the patellar tendon graft after ligament
      reconstruction really caused by "ligamentization" of the graft?
AB  - To test the hypothesis that extrinsic cells that infiltrate the devitalized
      patellar tendon (PT) synthesize type III collagen even in the environmental
      milieu of the native PT, we conducted the present experimental study using the
      rat in situ frozen-thawed PTs. Tissue culture showed no cell outgrowth from the
      tendons immediately after the freeze-thaw treatment. Analysis by RT-PCR showed
      that the expression level of type III procollagen mRNA in the frozen-thawed
      tendon was significantly higher than that in the sham-operated tendon at 6 and 12
      weeks. Immunohistological findings showed positive type III collagen staining
      around cells that had infiltrated the necrotized tendon at 3, 6, and 12 weeks. In
      addition, the elastic modulus of the in situ frozen-thawed tendon at 6 weeks was
      significantly less than that of the sham-operated tendon. The present study
      indicates that extrinsic cells that had infiltrated the devitalized PT
      synthesized type III collagen at least for 12 weeks even in the environmental
      milieu of the native PT. These findings raised the question whether the increase
      in type III collagen of the PT graft after ACL reconstruction is really caused by
      "ligamentization," the adaptation of the PT graft to the ACL environment.

PMID- 16816983
TI  - Comparing in vivo kinematics of anterior cruciate-retaining and posterior
      cruciate-retaining total knee arthroplasty.
AB  - The purpose of this study was to compare knee kinematics in patients with bi
      cruciate preserving total knee arthroplasty and posterior cruciate ligament (PCL)
      preserving total knee arthroplasty. Five knees received PCL-retaining
      arthroplasty and nine knees received both cruciate-retaining arthroplasty
      (ACL/PCL knees). We studied treadmill gait, stair stepping, and maximum flexion
      activities using lateral fluoroscopy and shape matching. For maximum flexion, the
      ACL/PCL knees showed 6 mm more posterior translation of the lateral condyle (p <
      0.05). For the stair activity, posterior translations of the lateral condyle were
      significantly greater in the ACL/PCL knees from 30 degrees to 70 degrees flexion
      (p < 0.05). Both condyles in the ACL/PCL knees showed greater posterior
      translation in the stance and swing phases of gait than in the PCL knees (p <
      0.05). Preserving both cruciate ligaments in total knee arthroplasty appears to
      maintain some basic features of normal knee kinematics in these activities.

PMID- 16816984
TI  - Recurrent shoulder instability among athletes: changes in quality of life, sports
      activity, and muscle function following open repair.
AB  - BACKGROUND: Recurrent anterior shoulder instability is a disabling condition in
      young athletes with possibly underestimated impact on quality of life and sports
      activity. Commonly used clinical scoring systems do not reflect the impairment of
      quality of life and sports activity. It was our aim to assess the return to
      preinjury levels of quality of life and sports activity as well as the changes in
      muscle function among competitive and recreational athletes. HYPOTHESIS: Patients
      suffering from post-traumatic recurrent shoulder instability have to adopt their
      participation in sports and therefore discover a reduction in quality of life.
      Open stabilization procedures are able to improve shoulder function and to reduce
      recurrence rates. However, return to preinjury shoulder function is not
      guaranteed. STUDY DESIGN: Retrospective longitudinal cohort study on 19
      consecutive athletes with recurrent, post-traumatic shoulder instability. All
      patients were treated with an open, capsulo-labral repair. The minimum follow-up
      was 24 months. METHODS: Life quality (SF12) and sports activity data (Athletic
      Shoulder Outcome Scoring System) were retrospectively collected for the time
      before injury (time 1) and for the time with recurrent instability (time 2). Two
      years after surgical stabilization (time 3), we followed our patients with
      different clinical outcome scores, rotator surface EMG measurement, isokinetic
      muscle strength testing, and a radiological evaluation. This design of a three
      step follow-up allowed for calculating the impact on quality of life and sports
      activity following the injury. RESULTS: Two years after surgery, the clinical
      scoring systems revealed good-to-excellent results in all patients. Quality of
      life physical component summary remained diminished by 9.2% despite the surgical
      procedure and was therefore significantly lower as compared to preinjury levels
      (p < 0.05). Sports activity was also significantly lower at the time of follow-up
      (p < 0.05). In this specific procedure, external rotation was not impaired
      postoperatively. EMG testing showed an overall reduction of muscle activity,
      however not significant. Isokinetic muscle strength was significantly diminished
      for external rotation and shoulder abduction. CONCLUSIONS: Open reconstruction
      procedures for recurrent shoulder instability can restore shoulder function and
      stability to near-normal values. Despite good-to-excellent clinical results,
      there is a significant impairment of quality of life and sports activity 2 years
      after surgery. Muscle activity and muscle strength are diminished. Recurrent
      shoulder instability remains a disabling condition to the young athlete. Future
      strategies have to emphasize restoration of quality of life, sports activity, and
      muscle function.

PMID- 16816987
TI  - Spelling in adults: the combined influences of language skills and reading
      experience.
AB  - One hundred and twelve university students completed 7 tests assessing word
      reading accuracy, print exposure, phonological sensitivity, phonological coding
      and knowledge of English morphology as predictors of spelling accuracy. Together
      the tests accounted for 71% of the variance in spelling, with phonological skills
      and morphological knowledge emerging as strong predictors of spelling accuracy
      for words with both regular and irregular sound-spelling correspondences. The
      pattern of relationships was consistent with a model in which, as a function of
      the learning opportunities that are provided by reading experience, phonological
      skills promote the learning of individual word orthographies and structural
      relationships among words.

PMID- 16816985
TI  - Arthroscopic posterior cruciate ligament reconstruction with hamstring tendon
      autograft: results with a minimum 4-year follow-up.
AB  - This study prospectively evaluates the outcomes at a minimum 4-year follow-up
      after PCL reconstruction using quadruple hamstring tendon autograft with an
      arthroscopic double fixation technique. During 1996-1999, hamstring tendon
      autograft graft has been used in 57 patients. Data from 52 patients who had been
      followed up completely were analyzed. All patients suffered from a grade 3 or
      higher grade of posterior drawer test and posterior sag sign with MRI image
      confirmation. Twelve knees had combined posterior and posterolateral instability,
      which were simultaneously reconstructed. Clinical assessments included Lysholm
      knee score, International Knee Documentation Committee (IKDC) scores, KT-1000
      instrumented test, thigh muscle assessment, and radiographic evaluation. The mean
      Lysholm score was 54 (40-65) and 91 (65-100) points (P<0.01) before and after
      surgery. Thirty (58%) patients could return to moderate or strenuous activity.
      The evaluation of AP translation has been performed with KT-1000. The average
      posterior displacement measured with KT-1000 was 11.69+/-2.01 mm preoperatively
      and 3.45+/-2.04 mm postoperatively. Forty-two (81%) patients demonstrated
      ligament laxity of less than 5 mm. Forty-two (81%) patients were rated as normal
      or nearly normal based on IKDC scores. Forty-six (88%) patients achieved a
      minimum of 80% recovery of extensor strength and 44 (85%) patients achieved a
      minimum of 80% recovery of flexor strength. Statistically significant differences
      existed in thigh girth, extensor strength, and flexor strength before and after
      reconstruction. Arthroscopic reconstruction for PCL with four-strand hamstring
      tendon graft produced satisfactory results. The semitendinosus and gracilis
      tendon graft is adequate in graft size, technically easier to perform and more
      reproducible, and had a satisfactory result.

PMID- 16816988
TI  - Citrus flavonoids in fruit and traditional Chinese medicinal food ingredients in
      China.
AB  - Flavonoids-enriched tissues of citrus such as peel, immature fruit and flower are
      consumed as culinary seasonings, tea ingredients in China for centuries. This
      HPLC quantitative study on the five citrus flavonoids, naringin, hesperidin,
      neohesperidin, sinensetin and nobiletin on a wide range of Chinese citrus fruits
      and several Traditional Chinese Medicinal food ingredients in East China,
      revealed a great diversity in flavonoid composition. Huyou peel (C. paradisi cv.
      Changshanhuyou) was found to be the best naringin (3.25%) and neohesperidin
      (2.76%) source; C. aurantium, a major ingredient of several citrus-related TCM,
      is also a suitable source of naringin and neohesperidin, and a good juice source
      for flavanone glycosides; the peel of Wenzhoumiju (C. unshiu) is one of the
      richest local species in hesperidin (up to 6.25%); Zaoju (C. subcompressa) has
      the highest content of nobiletin (0.59%), a polymethoxylated flavone. LC-ES-MS
      analysis of Zanthoxylum genus for flavonoids revealed for the first time the
      presence of significant amounts (0.74%) of hesperidin in the root of
      Liangmianzhen (Z. nitidum (Roxb.) DC), a relative of Sichuan pepper, which is a
      spice widely used in China.

PMID- 16816989
TI  - Long term effect of methylparathion contamination on soil microbial community
      diversity estimated by 16S rRNA gene cloning.
AB  - The long-term effects of methylparathion contamination on the diversity of soil
      microbial community was investigated by a culture-independent approach using
      small subunit ribosomal RNA (SSU rRNA) gene-based cloning. Microbial DNA
      extracted from both the control soil sample and methylparathion contaminated soil
      sample was subjected to PCR amplification with primers specific for bacterial 16S
      rRNA gene sequences. From the PCR amplification product, clone libraries were
      constructed for both samples. Phylotypes were defined by performing a restriction
      fragment length polymorphism analysis of 16S rRNA gene sequences with the enzymes
      RsaI and HhaI. A total of 603 phylotypes were identified among the 16S ribosomal
      DNA (rDNA) clones, the phylotype richness, frequency distribution (evenness) of
      the two clone libraries were compared by using a variety of diversity indices.
      Phylogenetic analysis of the sequences of the dominant phylotypes revealed that
      the bacterial communities changed noticeably. In the control soil, the dominant
      bacterial groups included a member of a novel bacterial division, the bacillus
      genus, and a member of alpha-proteobacteria, while in methylparathion
      contaminated soil, the dominant phylotypes were replaced by a member of the
      flexibactera-cytophaga-bacteroides division and two members of the gamma
      proteobacteria subdivision. This is the first report of the long-term effects of
      methylparathion (one of the major pesticides widely used in developing countries)
      on soil microbial community diversity and structure by a culture-independent
      method, and provides the evidences to assess the long-term environmental
      toxicological effects of methylparathion from the microbial community viewpoint.

PMID- 16816990
TI  - Pre/early adolescent onset of gambling and psychosocial problems in treatment
      seeking pathological gamblers.
AB  - This study examined the association between pre- or early-adolescent onset of
      gambling and severity of gambling and psychosocial problems in treatment-seeking
      adult pathological gamblers. A total of 236 pathological gamblers entering
      outpatient treatment completed the South Oaks Gambling Screen (SOGS) and the
      Addiction Severity Index (ASI). Using a quartile split procedure, gamblers who
      began gambling during their pre- or early-adolescent years (mean age of 10.5
      years; 1st quartile) were compared to gamblers who began gambling later in life
      (mean age of 23.0 years; 2nd to 4th quartiles). Compared to later onset gamblers,
      pre/early adolescent onset gamblers reported increased severity of psychiatric,
      family/social, and substance abuse problems on the ASI. They were more likely to
      report cognitive problems (trouble understanding, concentrating, or remembering),
      suicidal ideation, and a history of inpatient psychiatric treatment, and were
      less likely to be satisfied with their current living situation. Pre/early
      adolescent onset gamblers also reported earlier age of initiation of drinking,
      and were more likely to have received treatment for an alcohol use disorder, and
      to have used cannabis and cocaine in their lifetimes. Taken together, these data
      suggest that pre/early adolescent-onset of gambling may be a risk factor for
      later-life psychiatric, family/social, and substance abuse problems in treatment
      seeking pathological gamblers.

PMID- 16816991
TI  - Prevalence and diagnostic correlates of DSM-IV pathological gambling in
      psychiatric outpatients.
AB  - Studies of the prevalence of pathological gambling (PG) in psychiatric and
      substance abusing patients suggest that the disorder is not rare. Most studies
      have been of substance abusers in treatment, and the rate of PG has been found to
      be several times higher than the rate found in community based epidemiological
      surveys. However, only one study has examined the prevalence of PG in a
      heterogeneous sample of patients, and this was a study of psychiatric inpatients.
      We are not aware of any prior study of the prevalence of PG in a psychiatric
      outpatient sample. In the present report from the Rhode Island Methods to Improve
      Diagnosis and Services (MIDAS) project we examined the current and lifetime
      prevalence of PG in 1,709 psychiatric outpatients interviewed with a semi
      structured diagnostic interview that included a module to diagnose DSM-IV PG.
      Forty (2.3%) patients had a lifetime history of DSM-IV PG, all of whom had at
      least one other DSM-IV axis I disorder. Patients with PG had significantly more
      axis I disorders than patients without PG, and had significantly higher rates of
      bipolar disorder, social phobia, panic disorder with agoraphobia, alcohol use
      disorder, and other impulse control disorders. Possible reasons for the low
      prevalence of PG in our sample are discussed.

PMID- 16816992
TI  - Mental health outcomes and physical restraint use in nursing homes {private}.
AB  - We investigate the nexus between mental health outcomes in nursing home residents
      and the use of physical restraints. Previous studies in this area used limited
      statistical tests such as correlations and t-tests, that could not account for
      potential biases, such as residents who become mentally disturbed may be most
      likely to be restrained. We use propensity matching models that are less
      susceptible to this bias and data from the Minimum Data Set, representing
      approximately 2,000 residents over a period of 6 years. Our results clearly show
      that restrained residents are more likely to become more impaired with respect to
      cognitive performance, depression, and social engagement. We conclude that if
      facilities reduce restraint use then the prevalence of resident mental health
      problems will also likely decline.

PMID- 16816994
TI  - Genes and developmental stabiltiy of aggressive behavior problems at home and
      school in a community sample of twins aged 7-12.
AB  - Though behavioral genetic studies of aggression have implicated heritable and
      environmental factors, there is limited understanding of how these factors
      influence aggression across different settings and over time. Ratings for 732
      twins were collected from parents and teachers during middle childhood and early
      adolescence. Total aggression scores on the Child Behavioral Checklist (CBCL) and
      Teacher Report Form (TRF) were examined at each age, across both settings, and
      developmentally. In this sample, aggressive behavior was moderately to largely
      heritable at each age within the home (.76-.84) and school (.42-.61). Across each
      age, ratings by parents and teachers were moderately correlated (.19-.36).
      Genetic and environmental effects that were limited to a particular setting were
      important etiological factors for aggressive behavior consistently within each
      setting, while only genetic factors influenced levels of aggression across both
      settings. Stability during these ages was due to genetic effects common to each
      age and the persistence of child-specific environmental experiences within each
      setting. These results suggest that genetic and environmental influences on
      children's aggressive behavior are largely setting specific. Levels of aggression
      seen consistently across both settings are due to genetic influences.
      Developmentally stable levels of aggressive behavior result from genetic
      influences common to all ages and individual environmental influences whose
      effects persist across ages.

PMID- 16816995
TI  - Disability management practices in Ontario health care workplaces.
AB  - BACKGROUND: Workplace disability management programs are important in managing
      injury and disability. METHODS: A stratified random sample of 188 employers in
      health care workplaces (71 hospitals, 48 nursing homes, 42 private clinics, and
      27 community clinics) completed a mailed Organizational Policies and Practices
      (OPP) questionnaire. The OPP asked questions about eight workplace disability
      management practices. This article compares disability management practices
      across the four types of health care workplaces. RESULTS: A one-way analysis of
      variance for each of the eight practices demonstrated significant differences
      across facility types for all practices, except ergonomic practices. For
      unionized versus non-unionized workplaces, there were significant differences in
      all practices, except ergonomic practices. For workplaces with formal policies
      versus those without policies, there were significant differences in all
      practices, except people-oriented culture and safety diligence. CONCLUSION:
      Variations in disability management practices in health care workplaces need to
      be addressed to provide more effective prevention and treatment of work-related
      injuries and disability.

PMID- 16816996
TI  - Supervisors' views on employer responsibility in the return to work process. A
      focus group study.
AB  - BACKGROUND: Supervisors' attitudes and measures have been pointed out by
      employees to influence the return to work process. The purpose of this study was
      to explore supervisors' views on employer responsibility in the return to work
      process and factors influencing the support of sick-listed employees. METHOD: The
      focus group method was used. Six groups were conducted and each group met on one
      occasion. Twenty-three supervisors experienced in managing sick-listed employees
      participated. RESULT: Two different themes emerged; In "The Supervisor is the Key
      Person" the participants found themselves as being key persons, carrying the main
      responsibility for the rehabilitation of the sick-listed employees and for
      creating a good working environment, thus preventing ill health and sick-listing
      among the employees. In the second theme "Influential Factors in Rehabilitation
      Work" the participants described the rehabilitation work as a part of a greater
      whole influenced by society, demands and resources of the workplace and the
      interplay between all parties involved. CONCLUSION: The study gives us the
      supervisors' perspective on the complexity of the return to work rehabilitation.
      This knowledge could be invaluable and be used to improve the possibilities for
      developing successful collaboration in occupational rehabilitation.

PMID- 16816997
TI  - Preconception care and women with or at risk for diabetes: implications for
      community intervention.

PMID- 16816998
TI  - Oral health in women during preconception and pregnancy: implications for birth
      outcomes and infant oral health.
AB  - The mouth is an obvious portal of entry to the body, and oral health reflects and
      influences general health and well being. Maternal oral health has significant
      implications for birth outcomes and infant oral health. Maternal periodontal
      disease, that is, a chronic infection of the gingiva and supporting tooth
      structures, has been associated with preterm birth, development of preeclampsia,
      and delivery of a small-for-gestational age infant. Maternal oral flora is
      transmitted to the newborn infant, and increased cariogenic flora in the mother
      predisposes the infant to the development of caries. It is intriguing to consider
      preconception, pregnancy, or intrapartum treatment of oral health conditions as a
      mechanism to improve women's oral and general health, pregnancy outcomes, and
      their children's dental health. However, given the relationship between oral
      health and general health, oral health care should be a goal in its own right for
      all individuals. Regardless of the potential for improved oral health to improve
      pregnancy outcomes, public policies that support comprehensive dental services
      for vulnerable women of childbearing age should be expanded so that their own
      oral and general health is safeguarded and their children's risk of caries is
      reduced. Oral health promotion should include education of women and their health
      care providers ways to prevent oral disease from occurring, and referral for
      dental services when disease is present.

PMID- 16816999
TI  - Medically unnecessary emergency medical services (EMS) transports among children
      ages 0 to 17 years.
AB  - OBJECTIVES: Estimate the prevalence of medically unnecessary Emergency Medical
      Services (EMS) transports among children. METHODS: We linked EMS and emergency
      department (ED) billing records for all EMS-to-hospital transports of children
      originating in three counties in South Carolina between January 1, 2001 and March
      31, 2003. EMS responses resulting in no transport, transports to destinations
      other than the ED, or multiple trips for the same child in a single day could not
      be linked to ED data and were excluded. Medically unnecessary transports were
      identified with an algorithm using pre-hospital impressions, ED diagnoses and ED
      procedures. After exclusions, 5,693 transports of children between 0 and 17 years
      were available for study. RESULTS: Sixteen percent (16.4%) of all transports were
      medically unnecessary. Among children through age 12, upper respiratory and viral
      problems were the most common diagnoses associated with medically unnecessary
      transports; among older children, behavioral problems such as conduct disturbance
      or drug abuse were common. In multivariable analysis, the odds of an unnecessary
      transport were higher among younger children, non-white children, rural children,
      and children insured by Medicaid. CONCLUSIONS: The proportion of EMS transports
      which may be medically unnecessary is relatively modest compared to previous
      studies. However, many questions remain for future research. Further
      investigation should include examination of primary care availability and
      occurrence of unnecessary EMS use, existence of race-based disparities, and
      transports involving conduct disturbance and other behavioral conditions among
      children.

PMID- 16817000
TI  - Effect of "this side up" T-shirts on infant sleep position.
AB  - OBJECTIVES: To assess the impact of "This Side Up" T-shirts on parental practices
      in Nebraska. METHODS: A random sample of 3,210 Nebraska women who gave birth in
      2004, stratified by race/ethnicity, was mailed a brief questionnaire on their
      receipt of a T-shirt and SIDS risk reduction materials at their birthing
      hospital, and on infant sleep position. RESULTS: Response rates were low (25.9%),
      ranging from 10.6% for Native American mothers to 46.4% for White mothers. Half
      (52.0%) had received a T-shirt and 71.6% had received SIDS information. Two
      thirds (64.0%) reported that their infants slept on their backs; African-American
      and Hispanic infants were significantly less likely to back sleep. In univariate
      logistic regression models, African-American race, Hispanic ethnicity and
      maternal age 30-39 were significant negative predictors of back sleeping; White
      race and having received a SIDS brochure were positive predictors. In the fully
      controlled model African American and Asian race and Hispanic ethnicity were
      negative predictors of back sleeping; neither receiving SIDS information nor the
      infant T-shirt was significant. Effects of maternal age and a SIDS informational
      brochure appeared in models stratified by race/ethnicity. CONCLUSIONS: In these
      data, receiving an infant T-shirt was not related to how mothers placed their
      infants to sleep. Additional research is needed on effective methods of
      delivering targeted counseling and promoting safe sleep practices among families,
      particularly among racial and ethnic subgroups.

PMID- 16817001
TI  - Preconception care between pregnancies: the content of internatal care.
AB  - For more than two decades, prenatal care has been a cornerstone of our nation's
      strategy for improving pregnancy outcomes. In recent years, however, a growing
      recognition of the limits of prenatal care and the importance of maternal health
      before pregnancy has drawn increasing attention to preconception and internatal
      care. Internatal care refers to a package of healthcare and ancillary services
      provided to a woman and her family from the birth of one child to the birth of
      her next child. For healthy mothers, internatal care offers an opportunity for
      wellness promotion between pregnancies. For high-risk mothers, internatal care
      provides strategies for risk reduction before their next pregnancy. In this paper
      we begin to define the contents of internatal care. The core components of
      internatal care consist of risk assessment, health promotion, clinical and
      psychosocial interventions. We identified several priority areas, such as FINDS
      (family violence, infections, nutrition, depression, and stress) for risk
      assessment or BBEEFF (breastfeeding, back-to-sleep, exercise, exposures, family
      planning and folate) for health promotion. Women with chronic health conditions
      such as hypertension, diabetes, or weight problems should receive on-going care
      per clinical guidelines for their evaluation, treatment, and follow-up during the
      internatal period. For women with prior adverse outcomes such as preterm
      delivery, we propose an internatal care model based on known etiologic pathways,
      with the goal of preventing recurrence by addressing these biobehavioral pathways
      prior to the next pregnancy. We suggest enhancing service integration for women
      and families, including possibly care coordination and home visitation for
      selected high-risk women. The primary aim of this paper is to start a dialogue on
      the content of internatal care.

PMID- 16817002
TI  - Family planning services: an essential component of preconception care.
AB  - Family planning services are necessary for the widespread adoption of
      preconception care for two reasons. First, preconception care is more likely if
      pregnancies are planned, and family planning services encourage pregnancy
      planning. Second, family planning services usually include counseling, and
      counseling provides an opportunity to discuss the advantages of preconception
      care. However, the potential of family planning services to promote preconception
      care is limited by underutilization of these services and inadequate attention to
      preconception care during family planning visits. This article suggests ways to
      reduce these problems.

PMID- 16817003
TI  - Playing patient, playing doctor: Munchausen syndrome, clinical S/M, and ruptures
      of medical power.
AB  - This article deploys sadomasochism as a framework for understanding medical
      practice on an institutional level. By examining the case of the factitious
      illness Munchausen syndrome, this article analyzes the operations of power in the
      doctor-patient relationship through the trope of role-playing. Because Munchausen
      syndrome causes a disruption to the dyadic relationship between physicians and
      patients, a lens of sadomasochism highlights dynamics of power in medical
      practice that are often obscured in everyday practice. Specifically, this article
      illustrates how classification and diagnosis are concrete manifestations of the
      mobilization of medical power.

PMID- 16817004
TI  - Effects of unmeasured heterogeneity in the linear transformation model for
      censored data.
AB  - We investigate the effect of unobserved heterogeneity in the context of the
      linear transformation model for censored survival data in the clinical trials
      setting. The unobserved heterogeneity is represented by a frailty term, with
      unknown distribution, in the linear transformation model. The bias of the
      estimate under the assumption of no unobserved heterogeneity when it truly is
      present is obtained. We also derive the asymptotic relative efficiency of the
      estimate of treatment effect under the incorrect assumption of no unobserved
      heterogeneity. Additionally we investigate the loss of power for clinical trials
      that are designed assuming the model without frailty when, in fact, the model
      with frailty is true. Numerical studies under a proportional odds model show that
      the loss of efficiency and the loss of power can be substantial when the
      heterogeneity, as embodied by a frailty, is ignored.

PMID- 16817005
TI  - A comparison of models for dynamic life tables. Application to mortality data
      from the Valencia Region (Spain).
AB  - The graduation of mortality data aims to estimate the probabilities of death at
      age x, q ( x ), by means of an age-dependent function, whose parameters are
      adjusted from the crude probabilities that are directly obtainable from the data.
      However, current life tables have a problem, the need for periodic updates due to
      changes in mortality over short periods of time. The table containing mortality
      rates for different ages in different years, q ( xt ), is called a dynamic life
      table, which captures mortality variation over time. This paper proposes a review
      of the most commonly used dynamic models and compares the results obtained by
      each of them when applied to mortality data from the Valencia Region (Spain). The
      result of the comparison leads us to the conclusion that the Lee-Carter method
      offers the best results for both sexes, while that based on Heligman and Pollard
      functions provides the best fit for men alone. Our working method is of
      additional interest as it may be applied to mortality data for a wide range of
      ages in any geographical location, allowing the most appropriate dynamic life
      table to be selected for the case at hand.

PMID- 16817006
TI  - Dynamic path analysis-a new approach to analyzing time-dependent covariates.
AB  - In this article we introduce a general approach to dynamic path analysis. This is
      an extension of classical path analysis to the situation where variables may be
      time-dependent and where the outcome of main interest is a stochastic process. In
      particular we will focus on the survival and event history analysis setting where
      the main outcome is a counting process. Our approach will be especially fruitful
      for analyzing event history data with internal time-dependent covariates, where
      an ordinary regression analysis may fail. The approach enables us to describe how
      the effect of a fixed covariate partly is working directly and partly indirectly
      through internal time-dependent covariates. For the sequence of times of event,
      we define a sequence of path analysis models. At each time of an event, ordinary
      linear regression is used to estimate the relation between the covariates, while
      the additive hazard model is used for the regression of the counting process on
      the covariates. The methodology is illustrated using data from a randomized trial
      on survival for patients with liver cirrhosis.

PMID- 16817007
TI  - Analysis of longitudinal health-related quality of life data with terminal
      events.
AB  - Longitudinal health-related quality of life data arise naturally from studies of
      progressive and neurodegenerative diseases. In such studies, patients' mental and
      physical conditions are measured over their follow-up periods and the resulting
      data are often complicated by subject-specific measurement times and possible
      terminal events associated with outcome variables. Motivated by the "Predictor's
      Cohort" study on patients with advanced Alzheimer disease, we propose in this
      paper a semiparametric modeling approach to longitudinal health-related quality
      of life data. It builds upon and extends some recent developments for
      longitudinal data with irregular observation times. The new approach handles
      possibly dependent terminal events. It allows one to examine time-dependent
      covariate effects on the evolution of outcome variable and to assess
      nonparametrically change of outcome measurement that is due to factors not
      incorporated in the covariates. The usual large-sample properties for parameter
      estimation are established. In particular, it is shown that relevant parameter
      estimators are asymptotically normal and the asymptotic variances can be
      estimated consistently by the simple plug-in method. A general procedure for
      testing a specific parametric form in the nonparametric component is also
      developed. Simulation studies show that the proposed approach performs well for
      practical settings. The method is applied to the motivating example.

PMID- 16817008
TI  - Do provocateurs' emotion displays influence children's social goals and problem
      solving?
AB  - The social goals and social problem-solving of children who varied in social
      adjustment were examined in the context of hypothetical ambiguous provocation
      situations in which provocateurs' emotion displays were systematically
      manipulated. Children rated the importance of six different social goals and
      explained how they would solve the problems. Social adjustment was measured with
      rating and nomination sociometric procedures. Rejected-aggressive, rejected
      nonaggressive, average-nonaggressive, and popular-nonaggressive children showed
      both commonalities and differences in rating the six social goals, the relative
      importance of the six social goals, and social problem-solving depending on the
      provocateur's emotion display. When provocateurs were happy, there were few group
      differences, but when provocateurs were angry or sad, rejected-aggressive
      children: a) rated hostile/instrumental goals more positively; b) rated prosocial
      goals less positively; and c) made problem-solving responses that were less
      friendly than those of other children. Results are discussed in relation to
      Lemerise and Arsenio's (2000) model of emotion and social information processing.

PMID- 16817009
TI  - Implications of timing of maternal depressive symptoms for early cognitive and
      language development.
AB  - : Statistically, women, particularly pregnant women and new mothers, are at
      heightened risk for depression. The present review describes the current state of
      the research linking maternal depressed mood and children's cognitive and
      language development. Exposure to maternal depressive symptoms, whether during
      the prenatal period, postpartum period, or chronically, has been found to
      increase children's risk for later cognitive and language difficulties. The
      present review considers both the timing of maternal depression and the
      chronicity of mothers' depression on children's risk for cognitive and language
      delays. Infancy is frequently identified as a sensitive period in which
      environmental stimulation has the potential to substantially influence children's
      cognitive and language development. However, children's exposure to chronic
      maternal depression seems to be associated with more problematic outcomes for
      children, perhaps because depression interferes with mothers' ability to respond
      sensitively and consistently over time. Consistent with this expectation,
      interventions targeting parenting practices of depressed mothers have been found
      to increase children's cognitive competence during early childhood. The current
      review provides a synthesis of the current state of the field regarding the
      association between maternal depression and children's cognitive and language
      development during early childhood.

PMID- 16817010
TI  - Predictors of partner notification for C. trachomatis and N. gonorrhoeae: an
      examination of social cognitive and psychological factors.
AB  - Efforts to control chlamydial and gonococcal infections include notifying
      eligible sexual partners of possible infection, primarily by asking the diagnosed
      patient to notify their partners. This approach, known as patient referral, is
      widely used but poorly understood. The current study examined psychosocial and
      cognitive factors associated with patient referral among an urban, minority
      sample of 168 participants recently diagnosed with Chlamydia trachomatis or
      Neisseria gonorrhoeae. At a follow-up interview 1-month from diagnosis,
      participants were more likely to have notified all eligible partners if they had
      greater intention to notify at baseline (OR = 3.72; 95% CI = 1.34, 10.30) and if
      they had only one partner at baseline (OR = 4.08; 95% CI = 1.61, 10.31). There
      were also gender differences as well as differences based on type of partner
      (i.e., regular, casual, one-time). The implications of these findings for the
      design of programs to promote patient referral for sexually transmitted
      infections are discussed.

PMID- 16817011
TI  - Improvement in serial cardiopulmonary exercise testing following enzyme
      replacement therapy in Fabry disease.
AB  - BACKGROUND: Fabry disease is an X-linked genetic disorder resulting in the
      accumulation of glycosphingolipids in various organs, leading to exercise
      intolerance and early mortality. Enzyme replacement therapy (ERT) has recently
      been approved for use in Fabry patients. GOALS OF STUDY: To assess baseline
      cardiopulmonary exercise characteristics in both invasive and noninvasive tests
      and to study the impact of ERT on exercise. METHODS: A total of 15 patients with
      Fabry disease underwent baseline cardiopulmonary exercise tests. Six patients
      were randomized 2:1 to receive either ERT or placebo. We performed serial
      cardiopulmonary exercise tests at baseline and every 3 months over a period of at
      least 18 months. The baseline test was compared to the last two exercise tests
      for each patient. RESULTS: Mean age was 32 years. Mean VO2max was 1.680 +/- 0.67
      L/min and increased by 0.459 +/- 0.64 L/min in the patients receiving ERT. Mean
      VO2max was 1.462 +/- 0.25 L/min and decreased by 0.116 +/- 0.44 L/min in patients
      on placebo. Mean oxygen pulse (VO2/HR) increased by 1.71 with enzyme, but
      increased only 0.025 in patients taking placebo. Estimated stroke volume (SV)
      increased by 10 ml in patients on ERT. CONCLUSIONS: In this small cohort,
      exercise tolerance increased in patients receiving enzyme replacement therapy.
      Cardiopulmonary exercise testing is a useful test in measuring the response to
      therapy in Fabry disease patients.

PMID- 16817012
TI  - Genetic and biochemical characterization of 16 acute intermittent porphyria cases
      with a high prevalence of the R173W mutation.
AB  - Acute intermittent porphyria (AIP) is a metabolic disease with a variable
      prevalence among different countries. In some areas of southern Europe it remains
      to be fully evaluated. We undertook a genetic and biochemical study of 16
      unrelated Spanish AIP patients and relatives. The genetic analyses showed they
      harboured the following mutations in the porphobilinogen deaminase gene: R173W,
      G111R, L278P, L238P, R116W, R26C, 340insT, 730delCT, 691del30bp, and IVS14+1g>a.
      The mutation R173W was found in 6 patients (37.5%), including the only patients
      of our series with >3 recurrent porphyria attacks. While in clinical remission,
      all AIP patients exhibited sustained increased excretion of porphyrins and
      precursors. PBG excretion showed a high between-subject variation and was not
      related to erythrocyte PBG deaminase activity. The study of family members
      allowed the identification of 22 asymptomatic AIP carriers. These included 8
      persons harbouring the R173W mutation belonging to four different families. Six
      of these latent AIP subjects showed increased PBG elimination, and in two the
      urinary levels were >10-fold the normal limit. These results reinforce the
      hypothesis that the R173W mutation may have a high biochemical and clinical
      penetrance among AIP patients.

PMID- 16817013
TI  - Maple syrup urine disease: favourable effect of early diagnosis by newborn
      screening on the neonatal course of the disease.
AB  - BACKGROUND: In the rare autosomal recessive disorder maple syrup urine disease
      (MSUD) the accumulation of the branched-chain amino acids and their metabolic
      products results in acute and chronic brain dysfunction. Since 2002, MSUD has
      been part of the extended newborn screening programme in Germany and Austria.
      Early diagnosis and intervention during the presymptomatic or early symptomatic
      period should improve the outcome of the patients, which would make the case for
      screening for MSUD. AIM: The aim of the study was to evaluate the clinical course
      and alterations of marker metabolites during the first weeks of life in 10
      patients with classical MSUD detected by newborn screening (NBS) in comparison
      with the 10 youngest German patients diagnosed clinically. METHOD: Laboratory
      data as well as information on clinical course and management during the neonatal
      period were obtained retrospectively. RESULTS: Patients detected in NBS presented
      with lower plasma leucine concentrations at confirmation of diagnosis and less
      severe clinical symptoms. Lowering of leucine to below a critical threshold of
      1000 micromol/L was achieved earlier than in patients diagnosed on clinical
      grounds. CONCLUSION: After diagnosis in screening, treatment can be initiated
      before the occurrence of severe metabolic decompensation. However, a favourable
      effect can only be achieved with immediate transfer of the neonate to a metabolic
      centre for adequate treatment in case of a positive screening result.

PMID- 16817014
TI  - Mechanisms of N-acetylcysteine-driven enhancement of MK886-induced apoptosis.
AB  - N-Acetylcysteine (NAC), besides being a precursor of glutathione, has an array of
      other effects including an ability to scavenge free radicals, modulate gene
      expression and signal transduction pathways, and regulate cell survival and
      apoptosis. At concentrations lower than 20 mmol/L, NAC is nontoxic to cultured
      cells and can protect against apoptosis induced by a number of agents. A few
      recent reports, however, have indicated that NAC can also increase apoptosis.
      MK886, a 5-lipoxygenase activating protein (FLAP) inhibitor, induces apoptosis in
      many cell lines by an unknown mechanism that is independent of FLAP and
      lipoxygenase activity but is possibly related to effects on kinases such as Akt.
      In Jurkat T lymphocytes, NAC pretreatment (10 mmol/L) enhanced MK886-induced
      apoptosis by 2.4-fold. Following NAC-MK886 treatment, there was a significant
      increase in caspase-3 activity, and a decrease in mitochondrial transmembrane
      potential compared to MK886 alone. However, the extent of cytochrome c release
      was comparable between MK886 alone and MK886-NAC treatments. The enhancement of
      MK886-induced apoptosis by 10 mmol/L NAC appears to be partly related to a
      decrease in pH caused by this concentration of NAC, because an acidic environment
      favors activation of effector caspases and triggering of mitochondrial apoptosis.
      However, because neutralized NAC also enhanced apoptosis (1.6-fold), a direct
      role for NAC in augmenting the apoptotic pathways initiated by MK886 is
      suggested.

PMID- 16817015
TI  - Sodium chloride regulates Extracellular Regulated Kinase 1/2 in different tumor
      cell lines.
AB  - Perturbations of the extracellular ionic content by different hypo- or
      hyperosmolar stimuli initiate stress responses to maintain cell viability that
      include activation of Mitogen Activated Protein Kinases (MAPK) in cell lines
      derived from kidney epithelium. When hyperosmolar conditions induced by different
      salts occurred in the extracellular environment of tumor-derived cell lines, they
      activated the Extracellular Regulated Kinase 1/2 by increasing its
      phosphorylation steady-state on Thr202/Tyr204 in a time- and dose-dependent
      manner. It was found that Extracellular Regulated Kinase 1/2 activation is a
      consequence of selective phosphorylation by mitogen-activated protein kinase/ERK
      kinase. Changes in cell shape or in tubulin or actin cytoskeletal structure were
      not found, although cell growth arrest was observed as well as induction of
      apoptosis and modified cell migration ability that were dependent upon
      Extracellular Regulated Kinase 1/2 activation evidencing a critical role for the
      Extracellular Regulated Kinase 1/2 in mediating survival of cells in hyperosmotic
      conditions.

PMID- 16817016
TI  - Potential protein partners for the human TIMAP revealed by bacterial two-hybrid
      screening.
AB  - BacterioMatch Two-Hybrid System (Stratagene) was applied in order to identify
      potential human TIMAP interaction proteins in the lung. TIMAP highly expressed in
      endothelial cells and may be involved in endothelial cytoskeletal and barrier
      regulation. Seven TIMAP interacting partner proteins were identified. Four of
      identified proteins: cystein and glycine-rich protein 1, eukaryotic translation
      elongation factor 2, U5 snRNP-specific protein 116 kD, and solute carrier family
      3 member 2 are involved in actin cytoskeleton organization, cell adhesion or
      translation and transcriptional regulation.

PMID- 16817017
TI  - Induction of human UDP-glucuronosyltransferase 1A1 by cortisol-GR.
AB  - During the course of the study of UGT1A1 induction by bilirubin, we could not
      detect the induction of the reporter gene (-3174/+14) of human UGT1A1 in HepG2 by
      bilirubin (Mol. Biol. Rep. 31: 151-158 (2004)). In this report, we show the
      finding of the induction of the reporter gene of UGT1A1 by cortisol at 1 microM,
      a major natural cortico-steroid, with human glucocorticoid receptor (GR). RU486
      of a typical GR antagonist at 10 microM inhibited the induction by cortisol from
      5.9- to 1.8-fold. This result indicates that the induction by cortisol-GR is
      dependence on ligand-binding. This induction is caused by the UGT reporter gene
      itself, from the results of noinduction with control vector pGL2 (equal to pGV-C)
      in the presence of cortisol-GR. We confirmed that the induction of the reporter
      gene by cortisol is dependent on the position of proximal element (-97/-53) of
      UGT1A1. From this result, we concluded that the increase of corticosteroid in
      neonates must induce the elevation of UGT1A1 after birth and prevent jaundice.
      With the study of induction by corisol, we studied the influence of co-expression
      of PXR (pregnenolone xenobiotic receptor) with the UGT1A1 reporter gene and we
      could not find the induction of UGT1A1 expression in the presence of
      dexamethasone, rifampicin, or pregnenolone 16alpha-carbonitrile of the PXR
      ligands. These results suggest that the induction of UGT1A1 expression by GR is
      not mediated by PXR, unlike the induction of CYP3A4 through PXR.

PMID- 16817018
TI  - Identification of epitope on DNA-binding protein expressed in insect cell
      infected by baculovirus.
AB  - DNA-binding protein (DBP) is an early gene product produced during viral
      replication. Polyclonal anti-DBP was produced using rabbit by intradermal
      injections of Escherichia coli-expressed purified recombinant DBP. Prepared anti
      DBP completely blocked the replication of baculovirus in insect cells. The anti
      DBP binding to DBP was confirmed by both Western blotting with Tn-5B1-4 insect
      cell lysates as well as immunostained baculovirus-infected Tn-5B1-4 insect cells.
      To determine the anti-DBP epitope 12 peptides were synthesized and their specific
      binding activities were measured using ELISA. Based on specific-binding activity
      against anti-DBP the epitope was predicted to be between amino acid residues 248
      265 (QRMSVEDFDRLFEMDKID). Especially from 18 amino acid residues it was further
      to be narrowed between amino acid residues 260-265 (EMDKID) which showed a
      critical role in specific-binding activity.

PMID- 16817019
TI  - Cloning, chromosome mapping and expression analysis of an R2R3-MYB gene under
      expressed in maize hybrid.
AB  - R2R3-MYB transcription factors play important role in transcriptional controls
      during higher plant metabolism and development. In this study, an R2R3-MYB gene
      was isolated from maize according to an EST, which expressed differentially
      between a hybrid and the two parents on a cDNA chip. The full-length cDNA,
      designated by ZmMYBL1 (GenBank accession no. AY365033) consists of 1417
      nucleotides and contains an open reading frame of 828 bp. The deduced amino acid
      sequence contained two conserved MYB domains near its N-terminus, a conserved E1
      motif and an acidic Ser/Thr rich region toward its C-terminus. Southern blot
      analysis revealed ZmMYBL1 could be a single copy gene belonging to a multi-gene
      family in the maize genome. Expression analysis showed ZmMYBL1 transcripts
      accumulated in various tissues examined, with strong level in tassel and weak
      level in leaf. Also it was under-expressed in root, stem, and leaf of hybrid as
      compared with that of the two parents. ZmMYBL1 was mapped on maize chromosome
      bin7.03 between two SSR markers, bn1g339 and umc1865 using Yuyu22 recombinant
      inbred line population. A QTL for root average diameter in maize seedlings was
      also localized on the corresponding region of chromosome 7 within the interval
      ZmMYBLI-bnIg1805. A possible role of ZmMYBL1 and its relation to maize heterosis
      were discussed based on these results.

PMID- 16817020
TI  - Molecular cloning of a novel gene ZAhi-1 and its expression analysis during
      zebrafish gametogenesis.
AB  - Proto-oncogen Ahi-1 is closely related to a lot of human and mouse diseases. Ahi
      1 mutation will lead to leukemia in mice and Joubert syndrome in human beings. We
      have cloned the full cDNA sequence of Ahi-1 homologous in zebrafish, and RT-PCR
      results of ZAhi-1 in different tissues reveal that ZAhi-1 expressed highest in
      the mature gonad. In situ hybridization results of zebrafish gonad show that ZAhi
      1 only expressed in the early stages' gamete cells. RT-PCR analyses of mouse Ahi
      1 in different stages of spermatogenesis have been done according to the
      published Ahi-1 sequence, and the findings reveal that Ahi-1 is expressed in
      gamete of pachytene stage. It can then be safely concluded that Ahi-1 might take
      place in the spermatocyte from the early pachytene stage to the late pachytene
      stage.

PMID- 16817021
TI  - Cloning and characterization of a root-specific expressing gene encoding 3
      hydroxy-3-methylglutaryl coenzyme A reductase from Ginkgo biloba.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR, EC: 1.1.1.34) catalyzes
      the first committed step in mevalonic acid (MVA) pathway for biosynthesis of
      isoprenoids. The full-length cDNA encoding HMGR was isolated from Ginkgo biloba
      for the first time (designated as GbHMGR, GenBank accession number AY741133),
      which contained a 1713 bp ORF encoding 571 amino acids. The GbHMGR genomic DNA
      sequence was also obtained, revealing GbHMGR had four exons and three introns.
      The deduced GbHMGR protein showed high identity to other plant HMGRs and
      contained two trans-membrane domains and a catalytic domain. The three
      dimensional model of GbHMGR represented a typical spatial structure of HMGRs. The
      Southern blot and RT-PCR assay results indicated that GbHMGR belonged to a small
      gene family, and expressed in a tissue-specific manner with a low level
      expression being only found in root. The potential significance of GbHMGR gene
      was also discussed.

PMID- 16817022
TI  - Molecular cloning and characterization of the myostatin gene in croceine croaker,
      Pseudosciaena crocea.
AB  - Myostatin (MSTN) is a negative regulator of skeletal muscle mass and has a
      potential application in aquaculture. We reported the characterization of the
      myostatin gene and its expression in the croceine croaker, Pseudosciaena crocea.
      The myostatin gene had three exons encoding 376 amino acids. The cDNA was 1,906
      bp long with a 5'-UTR and 3'-UTR of 108 bp and 667 bp, respectively. A
      microsatellite sequence, CA(30) and CA(26) separated by TA, existed in the 3'
      UTR. Intron I and II were 343 bp and 758 bp in length, respectively. The deduced
      amino acid sequence was highly conserved, and had more than 90% identical to shi
      drum, gilthead seabream, striped sea-bass, white perch, and white bass proteins.
      The myostatin of croceine croaker had a putative amino terminal signal sequence
      (residues 1-22), a transforming growth factor-beta (TGF-beta) propeptide domain
      (residues 41-256), a RXXR proteolytic processing site (RARR, residues 264-267,
      matching the RXXR consensus site), and a TGF-beta domain (residues 282-376).
      There were 13 conserved cysteine residues in croceine croaker myostatin, nine of
      which are common to all TGF-beta superfamily members. The most conserved region
      of vertebrate myostatins is the TGF-beta domain, which was the mature bioactive
      domain of the myostatin protein. The myostatin gene was expressed not only in the
      skeletal muscle, but also in the other tissues.

PMID- 16817023
TI  - Cloning and characterization of a novel KRAB-domain-containing zinc finger gene
      (ZNF284L).
AB  - The zinc finger gene (ZNF) family plays an important role in the regulation of
      transcription. This study reports the cloning and characterization of a novel
      human zinc finger protein cDNA (ZNF284L) from fetal brain cDNA library. The
      ZNF284L cDNA is 2223 bp in length encoding a 593-aa polypeptide. The protein
      contains a KRAB A+b box and eleven C2H2 type zinc finger motifs. ZNF284L gene is
      mapped to 19q13.2-19q13.3 with 5 exons, and the expression pattern of ZNF284L
      gene was also examined by reverse transcription polymerase chain reaction (RT
      PCR). The transcripts were detected in the human lung, liver, pancreas, thymus,
      heart, placenta, spleen, prostate, ovary, small intestine and colon, but in human
      brain, skeletal muscle, kidney, testis and peripheral blood leukocyte, no
      expression was detected.

PMID- 16817024
TI  - Apolipoprotein E gene polymorphism and allele frequencies in the Lebanese
      population.
AB  - Apolipoprotein E (ApoE) genotypes were studied in order to determine the
      prevalence in the Lebanese population and compare it with other populations. DNA
      from 160 unrelated healthy donors from our HLA-bank was used. ApoE genotype was
      determined using the CardioVascular Disease (CVD) StripAssay (this assay is based
      on a Polymerase Chain Reaction-Reverse Hybridization technique). The prevalence
      of genotypes E3/3, E3/4, and E2/3 was found to be 69%, 26%, and 22%,
      respectively, and 0.6% for each of E2/4 and E4/4 genotypes. The Lebanese
      population tested showed similarities to earlier reported ApoE genotypic
      distributions (high E3 allele frequency) but also peculiar differences especially
      to some Arabic countries (total absence of E2 allele among Saudis) and other
      populations. This is the first report from Lebanon that will serve as a template
      for future investigations of the prevalence of ApoE alleles in association with
      various clinical entities.

PMID- 16817025
TI  - Regional cardiac dysfunction is associated with specific alterations in
      inflammatory cytokines and matrix metalloproteinases after acute myocardial
      infarction in sheep.
AB  - Cardiac remodeling following myocardial infarction (MI) is a maladaptive process,
      fundamental to the progression of ischemic heart failure. The extent of
      remodeling is influenced by mechanical stress, inflammatory response and
      activation of matrix metalloproteinases (MMPs). This study examined regional
      association between these parameters in response to acute MI. Coronary ligation
      was performed in ten sheep. Sonomicrometer transducers measured segmental length
      in the infarcted, border and non-infarcted region. Regional tissue samples
      obtained 3 h post MI from six sheep were analysed using RT-PCR, gelatin
      zymography and Western blot. Six sham-operated sheep served as controls.Region
      specific dilation and reduced contraction was associated with corresponding
      alterations in matrix molecules.IL-6 and MMP-9 mRNA were increased in the
      infarcted and border regions compared to controls.MMP-2 and TIMP-1 mRNA increased
      in non-infarcted myocardium and both correlated positively with segmental
      shortening. IL-6 mRNA levels, in contrast, were negatively associated with
      segmental shortening. In summary, inflammatory cytokines and MMPs are altered
      early after MI in a region-specific manner, and these changes correspond to acute
      regional myocardial dysfunction. Therapies for LV remodeling from the time of
      reperfusion may benefit from further understanding this portfolio of acute
      alterations.

PMID- 16817026
TI  - Reduced repolarization reserve due to anthracycline therapy facilitates torsade
      de pointes induced by IKr blockers.
AB  - BACKGROUND: Cytostatic agents such as anthracyclines may cause changes in the
      electrophysiologic properties of the heart. We hypothesized that anthracyclines
      facilitate life-threatening proarrhythmic side effects of cardiovascular and non
      cardiovascular repolarization prolonging drugs. METHODS AND RESULTS: The
      electrophysiologic effects of chronic administration of doxorubicin (Dox) were
      studied in ten rabbits, which were treated with Dox twice a week (1.5 mg/kg
      i.v.). A control group (11 rabbits) was given NaCl solution. Two of ten Dox
      rabbits died suddenly, the remaining animals showed mild clinical signs of heart
      failure after a period of six weeks. Echocardiography demonstrated a decrease in
      ejection fraction (pre treatment: 74 +/- 23% to post treatment: 63 +/- 16% (p
      <0.05)). In isolated hearts, action potential duration measured by eight
      simultaneously recorded monophasic action potentials (MAP) was similar in Dox and
      control hearts. However, in Dox rabbits, administration of the I(Kr)-blocker
      erythromycin (150-300 microM) led to a significant greater prolongation of the
      mean MAP duration (63 +/- 21ms vs 29 +/- 12 ms, p <0.05) and the QT interval (100
      +/- 32ms vs 58 +/- 17 ms, p <0.05) as compared to control. Moreover, I(Kr)-block
      led to a more marked increase of dispersion of MAP(90) in the Dox group as
      compared to control hearts (23 +/- 7ms vs. 9 +/- 4 ms). In the presence of
      hypokalemia more episodes of early afterdepolarizations and torsade de pointes
      occurred (p <0.05). CONCLUSION: Even during the early phase of chemotherapeutic
      treatment,before significant QT-prolongation is present,anthracyclines lead to an
      increased sensitivity to the proarrhythmic potency of I(Kr)-blocking drugs. Thus,
      anthracycline therapy reduces repolarization reserve and thereby represents a
      novel contributing factor for the development of life-threatening proarrhythmia.

PMID- 16817027
TI  - High-dose 17beta-estradiol treatment prevents development of heart failure post
      myocardial infarction in the rat.
AB  - OBJECTIVES: Prognosis of heart failure remains poor despite therapeutic advances,
      such as angiotensin converting enzyme inhibition or beta-receptor blockade. Thus,
      more effective forms of treatment are urgently needed. Since estrogens have been
      shown to modulate migration and proliferation of cardiac fibroblasts and to
      modulate the expression of estrogen receptors of cardiomyocytes we examined
      whether high-dose estrogen treatment can affect post-myocardial infarction left
      ventricular remodeling. METHODS: Female rats were treated with 17beta-estradiol
      (7.5 mg/90 d) or placebo for ten weeks, starting two weeks prior to experimental
      myocardial infarction. Eight weeks after infarction, in vivo echocardiographic
      and hemodynamic measurements as well as isolated heart perfusion were performed.
      RESULTS: In vivo, chronic estrogen treatment almost completely prevented the
      development of all signs of heart failure that occur in untreated infarcted
      hearts, such as increased left ventricular diameters (dilatation), reduced
      fractional shortening (systolic dysfunction) or increased left ventricular end
      diastolic pressure (diastolic dysfunction). In vitro, the right- (indicating
      structural dilatation) and downward (indicating left ventricular dysfunction)
      shift of left ventricular pressure-volume curves occurring in untreated infarcted
      hearts was completely prevented by estrogen. CONCLUSIONS: High dose estradiol
      treatment prevented development of post-MI remodeling, as assessed by in vivo and
      in vitro parameters of LV dysfunction. Estrogen may hold the potential of
      becoming a new form of heart failure treatment.However, the mechanisms
      responsible for this striking and unexpected beneficial action of estrogen in
      heart failure remain to be elucidated.

PMID- 16817028
TI  - Mechanics and chemotaxis in the morphogenesis of vascular networks.
AB  - The formation of vascular networks in vitro develops along two rather distinct
      stages: during the early migration-dominated stage the main features of the
      pattern emerge, later the mechanical interaction of the cells with the substratum
      stretches the network. Mathematical models in the relevant literature have been
      focusing just on either of the aspects of this complex system. In this paper, a
      unified view of the morphogenetic process is provided in terms of physical
      mechanisms and mathematical modeling.

PMID- 16817029
TI  - Status and perspective of sponge chemosystematics.
AB  - In addition to their pharmaceutical applications, sponges are an important source
      of compounds that are used to elucidate classification patterns and phylogenetic
      relationships. Here we present a review and outlook on chemosystematics in
      sponges in seven sections: Secondary metabolites in sponges; Further applications
      of bioactive compound research in sponges; Sponge chemotaxonomy; Pitfalls of
      sponge chemotaxonomy; The chemotaxonomic suitability of sponge compounds;
      Potential synapomorphic markers in sponges; and The future of sponge
      chemotaxonomy.

PMID- 16817030
TI  - Screening behavior in women at increased familial risk for breast cancer.
AB  - This multicenter study examined the adherence of high-risk women to screening
      recommendations for breast and ovarian cancer following consultation at a
      familial cancer clinic (FCC). Self-report questionnaires assessing recall of
      screening advice, tests undertaken, risk perception, anxiety (Impact of Events
      Scale) and demographics were mailed to 396 consecutive eligible women who had
      attended one of six FCCs a median of 3.6 years prior. Family history, genetic
      test results and screening recommendations were abstracted from medical records.
      182/266 (68.4%) women responded with 130 lost to follow-up. The proportions of
      women undertaking at least the recommended frequency of screening tests were:
      breast self examination (BSE) 50.4%, clinical breast examination (CBE) 66.0%,
      mammography 82.2%, transvaginal ultrasound (TVUS) 70.0%, CA125 84.0%. Factors
      associated with adherence to screening were: higher anxiety for BSE and CBE,
      being BRCA1/2 positive for CBE, older age, method of arrangement and having at
      least one affected first degree relative for mammography. Factors significantly
      associated with over-adherence were higher scores for anxiety for BSE and CBE and
      younger age (< 40 years) for TVUS. Between 41.3% (BSE) and 57.6% (CBE) of women
      incorrectly recalled their screening recommendations. A substantial minority of
      high-risk women do not adhere to screening advice. Strategies to improve the
      accuracy of recall of recommendations and the uptake of recommended screening are
      required.

PMID- 16817031
TI  - The added value of PMS2 immunostaining in the diagnosis of hereditary
      nonpolyposis colorectal cancer.
AB  - Identification and characterization of the genetic background in patients with
      the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome is important since
      control programmes can in a cost-effective manner prevent cancer development in
      high-risk individuals. HNPCC is caused by germline mismatch repair (MMR) gene
      mutations and the genetic analysis of HNPCC therefore includes assessment of
      microsatellite instability (MSI) and immunohistochemical MMR protein expression
      in the tumor tissue. MSI is found in >95% of the HNPCC-associated tumors and
      immunostaining using antibodies against the MMR proteins MLH1, MSH2, and MSH6 has
      been found to correctly pinpoint the affected gene in about 90% of the cases. The
      PMS2 antibody was the most recently developed and we have in a clinical material
      assessed the added value of PMS2 immunostaining in 213 patients with suspected
      hereditary colorectal cancer. All 119 MSS tumors showed retained expression for
      all four antibodies and PMS2 did thus not identify any underlying MMR defect in
      these cases. However, PMS2 immunostaining contributed to the characterization of
      the MMR defect in a subset of the MSI tumors. Concomitant loss of MLH1 and PMS2,
      which functionally interact in the MutLalpha complex, was found in 98% of the
      tumors from patients with germline MLH1 mutations. Among the 12 MSI-high tumors
      with retained expression of MLH1, MSH2 and MSH6, 8 tumors showed loss of PMS2
      staining, and mutations in MLH1 were identified in 2 and mutations in PMS2 in 3
      of these individuals. In summary, isolated loss of PMS2 was found in 8% of the
      MSI-high tumors in our series, including 8/12 previously unexplained MSI-high
      tumors, in which mutations either in MLH1 or in PMS2 were identified in five
      cases.

PMID- 16817032
TI  - The midline suboccipital subtonsillar approach to the hypoglossal canal: surgical
      anatomy and clinical application.
AB  - Primary lesions of the hypoglossal canal, such as hypoglossal schwannomas, are
      rare. No consensus exists with regard to the surgical approach of choice for
      treatment of these lesions. Usually, lateral transcondylar approaches have been
      used. The authors describe the surgical anatomy of the midline subtonsillar
      approach to the hypoglossal canal. This approach includes a midline suboccipital
      craniotomy, dorsal opening of the foramen magnum and elevation of ipsilateral
      cerebellar tonsil to expose the hypoglossal nerve and its canal. The midline
      subtonsillar approach permits a straight primary intradural view to the
      hypoglossal canal. There is no necessity of condylar resections. The surgical
      anatomy of the subtonsillar approach is described and illustrated by an example
      of a case.

PMID- 16817033
TI  - Molecular epidemiology of African swine fever virus studied by analysis of four
      variable genome regions.
AB  - Variable regions of the African swine fever virus genome, which contain arrays of
      tandem repeats, were compared in the genomes of isolates obtained over a 40-year
      period. Comparison of the size of products generated by polymerase chain reaction
      (PCR) from four different genome regions, within the B602L and KP86R genes and
      intergenic regions J286L and BtSj, placed 43 closely related isolated from
      Europe, the Caribbean, West and Central Africa into 17 different virus sub
      groups. Sequence analysis of the most variable fragment, within the B602L gene,
      from 81 different isolates distinguished 31 sub-groups of virus isolates which
      varied in sequence and number of a tandem repeat encoding 4 amino acids. Thus,
      each of these analysis methods enabled isolates, which were previously grouped
      together by sequencing of a more conserved genome region, to be separated into
      multiple sub-groups. This provided additional information about strains of
      viruses circulating in different countries. The methods could be used in future
      to study the epidemiology and evolution of virus isolates and to trace the
      sources of disease outbreaks.

PMID- 16817035
TI  - Maribor General Hospital from its foundation until World War II.
AB  - The author describes the history of Maribor General Hospital from its foundation
      in 1799 until the beginning of World War II. In 1799 the magistrate of the town
      of Maribor issued a memorandum regarding the establishment of a town hospital in
      the renovated building of the town hospice, providing space for 24 patients. The
      work of the hospital was carried out in the former hospice building until 1855.
      In the period between its establishment and eventual relocation 26 beds were
      added. The last two decades of the hospital's operation at the original location
      were marked by the assiduous work of the town's physicist, Dr. Anton Kuker. In
      the first half of the 19th century, the population of Maribor grew rapidly as a
      consequence of the construction of the Southern Railway. The town authorities
      therefore purchased the Prosenjak family villa in the Magdalena suburbs and
      relocated the hospital to it in 1855, providing 28 rooms for 110 patients. For a
      whole century, the care of patients was taken over by the Daughters of Charity of
      Saint Vincent de Paul. The hospital was soon admitting over 1000 patients a year,
      the most common complaints being pulmonary catarrh, gastritis and fever. In 1872,
      when the Master of Surgery Feliks Ferk joined the hospital, the internal
      "medical" and the "external" surgical departments were formed. Although medical
      studies were not easily accessible, there were a number of Slovene physicians
      working in the hospital and the town in that period. In the last decades of the
      19th century, the hospital was often renovated and enlarged. The infrastructure
      (telephone, water supply system, heating, lighting) had also been modernized
      before World War I. In 1914, the first X-ray apparatus was purchased. Between the
      wars, the hospital's development was boosted by recruitment of the Slovene
      physicians Ivan Matko, Mirko Cernic, Janko Dernovsek and Hugon Robic. The initial
      external and medical departments split into several departments: internal
      medicine, surgery, dermatovenereology, gynecology and obstetrics, infectious
      diseases, X-ray institute, autopsy department, and pulmonary department. A
      department of otology and ophthalmology was also founded. After the
      disintegration of the Austro-Hungarian Empire, Maribor Hospital was no longer
      overshadowed by the formerly dominant regional hospital in Graz in present-day
      Austria. A greater number of patients entailed more rapid professional
      development. At the beginning of World War II, the hospital comprised six
      departments, two institutes and a dispensary, and had an elaborate administrative
      structure with numerous support services.

PMID- 16817036
TI  - Treatment of ruptured intracranial aneurysms: report from a low-volume center.
AB  - BACKGROUND: The aim of this retrospective analysis was to present our experience
      and results in treating subarachnoid hemorrhage due to ruptured intracranial
      aneurysms at a neurosurgical department with a small annual number of cases (i.e.
      a low-volume center) and to discover which factors could influence treatment and
      reliably predict the outcome of hemorrhage. METHODS: All patients with aneurysmal
      subarachnoid hemorrhage treated at our department between 1973 and 2003 were
      retrospectively analyzed. We performed 293 operations and 21 endovascular
      procedures. In the majority of patients we excluded the aneurysm from circulation
      by placing a clip on the aneurysmal neck. Relevant data were obtained on
      patients' performance, imaging studies, treatment and outcome. RESULTS: According
      to the Hunt & Hess grade, the majority of patients were in groups 1 or 2.
      Perioperative mortality was 3%. Postoperative mortality due to complications
      related to subarachnoid hemorrhage was 10%. Vasospasm was detected in 18% of
      patients and was a direct cause of death in 5%. The outcome was good in 68%
      (grades 4 or 5 on the Glasgow outcome scale). In multivariate analysis, the Hunt
      & Hess grade, age and clinical vasospasm all had important predictive value for
      the outcome. CONCLUSIONS: The results of treatment in our series of patients fall
      within reported norms and are comparable to results from other low-volume
      centers. For successful treatment of aneurysmal subarachnoid hemorrhage, fast
      diagnosis, correct surgical or endovascular treatment and proper intensive pre-
      and postoperative care are of utmost importance.

PMID- 16817037
TI  - The frequency of neonatal morbidity after exposure to antiepileptic drugs in
      utero: a retrospective population-based study.
AB  - OBJECTIVES: To investigate the frequency of malformations, fetal growth
      retardation, cerebral hemorrhage and neonatal withdrawal symptoms in newborns
      exposed to antiepileptic drugs (AEDs) in utero. DESIGN: Population of the
      northeastern part of Slovenia (pregnant women and newborns between 1998 and
      2002). METHODS: Data on newborns born between 1998 and 2002 of 37 epileptic
      mothers taking AEDs in pregnancy, of 32 epileptic mothers not taking AEDs in
      pregnancy and of 211 mothers healthy in pregnancy were ascertained from hospital
      obstetric and neonatal records and included in the study. The health status of
      270 newborns was assessed. MAIN OUTCOME MEASURES: frequency of congenital
      malformations, growth retardation (SFD), intracranial hemorrhage, feeding
      problems and withdrawal symptoms. RESULTS: In the group not exposed to
      antiepileptic drugs (32 neonates), two (2.9%) had germinal matrix hemorrhage
      grade I, one (1.4%) was small for date (SFD) and one (1.4%) had feeding problems.
      In the group exposed to antiepileptic drugs (37 neonates), nine (13%) had
      germinal matrix hemorrhage grade I, six (8.6%) were SFD, five (7.24%) had feeding
      problems, four (5.8%) had withdrawal symptoms and three (4.3%) "macro" congenital
      anomalies. Among neonatal problems in the control non-exposed group of newborns
      of 211 healthy women we identified 23 (10.9%) newborns who were SFD, 5 (2.4%)
      cases with germinal matrix hemorrhage grade I, 5 (2.4%) cases with major
      congenital malformations and 7 (3.3%) cases with feeding problems. CONCLUSIONS:
      Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is
      associated with increased risk of neonatal morbidity. In our study a particularly
      significant connection was established between carbamazepine therapy during
      pregnancy and cerebral hemorrhage in the neonates.

PMID- 16817039
TI  - Effect of etidronate in preventing periprosthetic bone loss following cemented
      hip arthroplasty: a randomized, double blind, controlled trial.
AB  - INTRODUCTION: Periprosthetic bone loss occurs after insertion of a total hip
      prosthesis and is often a result of stress shielding or altered loading of the
      proximal femur. Preventing the bone loss, which may threaten the prosthesis
      survival, with an antiresorptive drug would be highly advantageous. MATERIALS AND
      METHODS: Our study investigated the effect of cyclic etidronate therapy on
      periprosthetic, contralateral hip, and spine bone mineral density (BMD) in a one
      year, prospective, randomized, double-blind study in 31 patients after cemented
      hip arthroplasty. Etidronate was taken orally in a regimen repeated every 14
      weeks, and periprosthetic BMD was measured with dual energy X-ray absorptiometry
      (DXA) in the total periprosthetic area and in the seven Gruen zones at 1 week
      (baseline), 6 weeks, 3 months, 6 months, and 12 months postoperatively. RESULTS:
      In the etidronate group there were significant temporal BMD decreases measured in
      Gruen zones 2, 3, 6, and 7 and in the entire proximal femur; the greatest
      decrease was 12.9% and was measured in zone 7 at six months. Also in the
      etidronate group, there was a significant 2.8% temporal BMD increase in the spine
      at 12 months. In the placebo group there were significant temporal BMD decreases
      measured in Gruen zones 1, 2, 3, 5, 6, and 7 and in the entire proximal femur;
      the greatest decrease was 25.5% and was measured in zone 7 at 12 months. There
      were no significant differences between the mean BMD measurements of the
      etidronate and placebo groups. CONCLUSION: These findings suggest that cyclic
      etidronate therapy has no significant effect in suppressing periprosthetic bone
      loss after cemented hip arthroplasty.

PMID- 16817038
TI  - Acquired cystic kidney disease and arterial hypertension in hemodialysis
      patients.
AB  - BACKGROUND: Acquired cystic kidney disease (ACKD) and arterial hypertension (AH)
      are both frequent complications in hemodialysis (HD) patients. Until now, AH has
      not been described as a complication of ACKD. PATIENTS AND METHODS: Our study
      included 86 HD patients (46 men and 40 women; mean age 51.3 years; mean duration
      of HD treatment 55.3 months). Their native kidneys were examined with an ATL-HDI
      3000 ultrasound device (2-4 MHz convex probe). Depending on the number of cysts
      in the kidney, the manifestations were divided into three grades: grade 0: no
      cysts; grade 1: fewer than ten cysts in both kidneys; grade 2: more than ten
      cysts in both kidneys. Blood pressure was measured 30 minutes before and after
      HD. Mean one-month values were analyzed. AH was defined as systolic blood
      pressure > or = 150 mmHg, diastolic blood pressure > or = 90 mmHg and/or
      antihypertensive treatment. The diameter of the inferior vena cava (indicator of
      dry weight) was measured with the same ultrasound device as the kidneys three
      hours after HD. RESULTS: ACKD was present in 48 (55.8%) patients, there was no
      statistically significant difference regarding sex. Twenty-four (50%) patients
      had grade 1 ACKD and 24 (50%) grade 2 ACKD. Sixty-eight (79.1%) patients suffered
      from AH, which was significantly more common among the men (P = 0.048). AH was
      detected before HD in 68 (79.1%) patients and in 54 (62.8%) patients also after
      HD. Thirty-nine (45.3%) patients suffered simultaneously from ACKD and AH; 22
      (56.4%) of them were men and 17 (43.6%) women. No significant correlation between
      AH and ACKD was established. The prevalence and grade of ACKD were significantly
      associated with the duration of dialysis treatment (P < 0.01). Multiple
      regression analysis detected a significant correlation only between AH and the
      diameter of the inferior vena cava (P < 0.05). CONCLUSIONS: ACKD is common in HD
      patients. Its prevalence and grade increase with the duration of dialysis
      treatment. ACKD is not associated with AH. There is a correlation between the
      diameter of the inferior vena cava, as a factor of circulating fluid volume, and
      AH in HD patients.

PMID- 16817040
TI  - Polyneuropathy in hemodialysis patients: the most sensitive electrophysiological
      parameters and dialysis adequacy.
AB  - BACKGROUND: Polyneuropathy (PNP) is a common complication in hemodialysis (HD)
      patients. Electrophysiological parameters are quantitative indices of its
      severity. The aim of our study was to find the prevalence of pathologic
      electrophysiological parameters, to assess their prevalence in relation to
      duration of HD treatment and age, to establish which parameters are the most
      sensitive in demonstrating PNP and to find an association between them and HD
      adequacy. PATIENTS AND METHODS: We included 84 (50 men, 34 women) HD patients
      (average age 47.32 years; average dialysis duration 62.56 months) and divided
      them into three groups according to the duration of HD treatment. Each group was
      further divided into two subgroups according to age. We included
      electrophysiological parameters for evaluation of motor and sensory nerve
      functions (Medelec Sapphire Premiere device). HD adequacy was measured with urea
      kinetic modeling (Kt/V). RESULTS: PNP was found in 77 (91.6%) HD patients and was
      more common in men (P < 0.016). The association between the number of pathologic
      electrophysiological parameters and age (P < 0.0001), duration of HD treatment (P
      < 0.009) and HD adequacy (P < 0.0001) was statistically significant. The most
      sensitive electrophysiological parameter was the latency of the F wave
      (pathologic values of F wave latency in the lower limbs in 86% patients and in
      the upper limbs in 49%). Sensory conduction velocities and the amplitudes of the
      orthodromic sensory action potentials and the M wave were also sensitive
      parameters. The F wave latency of different nerves was associated with dialysis
      adequacy. CONCLUSIONS: PNP is frequent in HD patients and is associated with age
      and duration of dialysis treatment. The most sensitive electrophysiological
      parameter of PNP is F wave latency, which may also be used as a parameter of
      dialysis adequacy.

PMID- 16817041
TI  - Hereditary diffuse palmoplantar keratodermas in Slovenia: epidemiologic foci in
      remote rural areas.
AB  - BACKGROUND: Previous studies carried out in Slovenia revealed a high frequency of
      cases of hereditary diffuse palmoplantar keratodermas (DPPK). The relatively
      small total population of about two million in a small territory and an efficient
      public health service were favorable preconditions for such a study. METHODS:
      Existing hospital and outpatient department records served as starting points.
      Patients were invited to come for a follow-up examination, and visiting the
      patients at their homes enabled us to gather further data. Thus efforts were made
      to include all patients with hereditary DPPK in Slovenia. RESULTS: Altogether 170
      DPPK patients were detected, giving a prevalence of 8.3 per 100,000 inhabitants.
      The patients originated from remote, mostly mountainous districts, where the
      local DPPK prevalence highly significantly exceeded the average Slovene
      prevalence. The segregation ratio showed an autosomal dominant mode of
      inheritance. The percentage of persons affected was 34.4% (95% confidence
      interval 29.8-39.4), lower than expected for autosomal dominant inheritance (the
      difference is highly significant, P < 0.00001; exact binomial test). CONCLUSION:
      One autosomal dominant gene alone does not fully explain the transmission of the
      disorder to siblings. Evidence is produced that additional factors are necessary
      for the transmission of this genetic condition. The degree of consanguinity and
      the physical pressure on palms and soles seem to play an important part. It is
      reasonable to expect that molecular-biology studies linked to the epidemiological
      data could contribute to the solution of the problem.

PMID- 16817042
TI  - [Posterior capsule opacification after phacoemulsification in patients with
      rheumatoid arthritis].
AB  - PURPOSE: To assess the posterior capsule opacification (PCO) rate after
      phacoemulsification with polyacrylic intraocular lens (IOL) implantation in
      patients with rheumatoid arthritis (RA) compared with the controls, and to assess
      whether preoperative activity of RA is associated with a higher incidence of PCO.
      METHODS: 24 eyes of 20 RA patients operated in a period of 4 years were included
      in our study. A control group of 20 eyes from 20 health subjects were also
      included in our study. All procedures were performed by a single surgeon with the
      same surgical technique and postoperative medication. RESULTS: One year
      postoperatively in two eyes (8.3%) of RA-patients lens epithelial cells (LEC)
      migration of grade 1 was observed, in controls also in two eyes (10%). No
      correlation was observed between age, duration of RA or preoperative activity of
      RA and the PCO rate. CONCLUSION: Following acrylic IOL implantation, the PCO rate
      one year after surgery was 8.3% in RA patients and 10% in controls. RA patients
      present no higher risk for PCO development than controls.

PMID- 16817043
TI  - Anatomical peculiarities of the cavo-tricuspid isthmus in the human heart.
AB  - The cavo-tricuspid isthmus is the term for the part of the right atrium between
      the ostium of the inferior vena cava and its border--the Eustachian ridge on one
      side and the tricuspid valve on the other side. In this area lie the coronary
      sinus ostium with its Thebesian valve, the fibers of Chiari (10%), and ostia of
      the deep cardiac veins--the Thebesian veins in close relation to the coronary
      sinus ostium (35%). Pacing of the coronary sinus is very often used during the
      treatment of cardiac arrhythmias; radiofrequency catheter ablation in cases of
      permanent atrial tachycardia is successfully performed through the coronary
      sinus; during certain cardiosurgical procedures, cardioplegia is performed by
      retrograde perfusion of the myocardium through the coronary sinus. Knowing and
      recognizing certain anatomical peculiarities of the structures in this part of
      the right atrium may be interesting for clinical practice.

PMID- 16817044
TI  - Does endoscopic ultrasound staging already allow individual treatment regimens in
      gastric cancer.
AB  - AIM: The aim of our study was to evaluate the accuracy of preoperative TNM
      staging with endoscopic ultrasound (EUS) in gastric cancer patients in comparison
      with the pathohistological stage of the resected specimen, and to determine the
      possible implications of EUS for individualized treatment of gastric cancer
      patients at our institution. PATIENTS AND METHODS: The study included 82 patients
      operated for resectable gastric cancer between January 1(st) 2001 and July 1(st)
      2003 at the Maribor Teaching Hospital Department of Abdominal and General
      Surgery. The EUS stage was assessed preoperatively at the Endoscopical Unit, and
      the pathohistological stage in the resected specimen was determined
      postoperatively at the Department of Pathologic Morphology according to
      recommended standards. RESULTS: Comparison of EUS and pathohistological
      assessments revealed accuracy of EUS staging for locoregional tumor infiltration
      (category T) in 68% of patients. The accuracy of EUS staging was 68% for T1, 69%
      for T2, 69% for T3 and 60% for T4. Lymph nodes (category N) were correctly staged
      with EUS in 57% of cases. The EUS stage was correct for lymph nodes with no
      metastases (N-) in 40% of cases, and for lymph nodes with metastases (N+) in 90%.
      There was no significant difference in accuracy of EUS staging with regard to
      tumor site (P = 0.768) or tumor size (P = 0.766). CONCLUSIONS: According to our
      results the accuracy of EUS staging matched pathohistological staging with regard
      to tumor infiltration and lymph node stage in 68% and 57% of cases respectively.
      Underestimation of the final T2 and T3 stages as T1 stage by EUS presents a
      problem regarding the consistency of EUS examination at our institution,
      particularly with respect to individual treatment for early gastric cancer. The
      present uncertainty in EUS stage reliability makes it necessary to have a
      strategy of radical resection with D2 lymphadenectomy in patients within EUS
      stages T1-T3, with additional CT examinations in more advanced EUS stages in
      order to visualize the circumstances of tumor growth. Nevertheless, EUS provides
      an opportunity for the surgeon to gain more insight into the loco-regional
      circumstances of the gastric tumor process. For development of individual modes
      of treatment based on EUS staging, a more reliable assessment of EUS stage is
      mandatory.

PMID- 16817045
TI  - Women and men with unstable angina and/or non-ST-elevation myocardial infarction.
AB  - BACKGROUND: In unstable angina and/or non-ST-elevation myocardial infarction
      (UA/NSTEMI), sex-related differences in outcomes are less well known than in ST
      elevation myocardial infarction (STEMI), where women experience worse outcomes
      than men. Our aim was a prospective comparison between men and women with
      UA/NSTEMI of baseline characteristics, in-hospital complications, mortality,
      reinfarctions and combined endpoint of mortality and/or reinfarction during
      hospital stay, at 30 days and at six months. METHODS: Initial medical treatment
      was given to 92 men and 47 women with UA/NSTEMI. Percutaneous coronary
      interventions (PCI) were performed within the first 48 hours in cases of
      recurrent chest pain and/or rhythmic and/or hemodynamic instability. RESULTS:
      Women were significantly older (66.6 +/- 9.6 vs. 59.7 +/- 10.6, P = 0.0001), less
      physically active (76.6% vs. 91.3%, P = 0.035), with significantly more frequent
      arterial hypertension (78.7% vs. 51%, P = 0.0039) and insulin-treated diabetes
      (17% vs. 5.4%, P = 0.0341), but with less likely prior MI (21.3% vs. 48.9%, P =
      0.003), smoking (10.6% vs. 32.6%, P = 0.009) and dyslipidemia with HDL
      cholesterol < 1.0 mmol/L (25.5% vs. 46.4%, P = 0.015) than men. Though medical
      and invasive treatments were similar in both sexes, women were at significantly
      increased risk of in-hospital pulmonary edema (OR 4.16, 95% CI 1.51 to 11.45) but
      not at increased risk of adverse in-hospital, 30-day and six-month outcomes in
      comparison with men. CONCLUSIONS: Women with UA/NSTEMI, being significantly older
      and with more comorbidity, were at significantly increased risk of in-hospital
      heart failure but not at increased risk of in-hospital, 30-day and six-month
      adverse outcomes when compared with men, despite their similar treatments.

PMID- 16817046
TI  - Long-term results after open Bankart operation for anterior shoulder instability.
      A 3- to 16-year follow-up.
AB  - The open Bankart procedure is still considered the gold standard for patients
      with recurrent posttraumatic anterior shoulder instability. The purpose of this
      retrospective study was to analyze long-term results after open Bankart procedure
      in 83 patients that were operated between 1987 and 2000 and to evaluate the rate
      of recurrent instability, level of function and range of motion. The mean follow
      up time was 9 (3-16) years. The postoperative recurrence rate including
      subluxations was 12%. The mean Constant score was 77 and the mean Rowe score was
      63. Average loss of external rotation in 90 degrees of abduction was 19 degrees .
      The results were disappointing in terms of stability and function. In the absence
      of longterm prospective studies on newer arthroscopic techniques, the decision on
      the reconstruction method must still be based on the surgeon's experience and the
      patient's choice.

PMID- 16817047
TI  - Serum CA 125 levels and lymph node metastasis in patients with endometrial
      cancer.
AB  - The aim of this study was to evaluate the correlation of preoperative serum CA
      125 levels and lymph node metastasis in patients with endometrial cancer.
      Preoperative levels of serum CA 125 were determined in 64 patients with
      endometrial cancer treated with total abdominal hysterectomy with a lymph node
      dissection as initial therapy. Lymph node status, determined by histopathology,
      was correlated with both normal and elevated CA 125 levels, determined
      preoperatively. A serum CA 125 level of >30 IU/ml was considered elevated. There
      were five patients (7.8%) with pelvic or paraaortic lymph node metastases and 59
      patients (92.2%) without nodal metastases. In all five patients with lymph node
      metastases, serum CA 125 was within normal limits. Preoperative serum CA 125
      levels were above normal in eight lymph node-negative patients. In the remaining
      group of 51 node-negative patients, serum CA 125 levels were within normal
      limits. Among the five lymph node-positive patients, four had endometrioid and
      one had serous papillary cancer. One patient had histologic grade 2 tumor and
      four patients had histologic grade 3. Preoperative serum CA 125 levels do not
      offer any information for predicting lymph node metastasis in patients with
      endometrial cancer.

PMID- 16817048
TI  - Cystatin C versus creatinine as a marker of glomerular filtration rate in the
      newborn.
AB  - AIM: Serum cystatin C (cysC) has been proposed as a promising endogenous marker
      of glomerular filtration rate (GFR) in adults and children. The aim of this study
      was to determine the reference values of cysC at birth and three days later in
      comparison with creatinine (Cr) and Schwartz's estimated clearance. PATIENTS AND
      METHODS: 75 newborns (42 boys, 33 girls) were enrolled in the study. The
      gestational age ranged from 34 to 41 weeks, and the birth weight from 2070 to
      4410 g. Blood samples were taken from the umbilical cord at birth and from a
      peripheral vein three days after birth. CysC and Cr were measured in all serum
      samples and values analyzed in different subgroups of neonates according to sex,
      gestational age, birth weight, umbilical blood pH, the influence of bilirubin,
      hemoglobin and hydration state. The Mann-Whitney U-test and Wilcoxon's analysis
      were used. RESULTS: At birth, serum cysC values ranged from 1.38 to 3.23 mg/l,
      not significantly decreasing after 3 days of life. Cr levels, determined
      simultaneously at birth, ranged from 34 to 99 mumol/l and were also not
      significantly different from day 3 levels. Both CysC and Cr levels were
      independent of sex, gestational age, birth weight, bilirubin levels and hydration
      state. CysC correlated positively only with the hemoglobin level (r = 0.28, P =
      0.01) and negatively with cord blood pH (r = -0.40, P = 0.001), similarly to Cr.
      Significant correlation was found between cysC and Cr in umbilical cord blood (r
      = 0.30, P = 0.006) and day 3 blood samples (r = 0.37, P = 0.001). No correlation
      was found between 1/cysC and Schwartz GFR in cord blood (r = 0.18, P = 0.18), but
      correlation became significant in day 3 blood samples (r = 0.27, P = 0.02).
      CONCLUSION: This study suggests that cysC is not more sensitive than Cr as a
      marker of GFR in the newborn.

PMID- 16817049
TI  - Infected femoral pseudoaneurysms from intravenous drug abuse in young adults.
AB  - Intravenous or parenteral drug abuse is the most common cause of infected femoral
      artery pseudoaneurysms (IFAP). This complication of intravenous drug abuse is not
      only limb threatening but can also be life threatening. The management of IFAP is
      difficult and controversial. Generally speaking, ligation and excision of the
      pseudoaneurysm without revascularization is accepted procedure in the majority of
      patients, with acceptable morbidity and low rate of limb loss. However, it is not
      an appropriate procedure for cases of acute interruption of the femoral artery
      flow, where a high probability of amputation is expected. We present four cases
      of young patients (average 19.5 years, range 17-24) with IFAP, where primary
      reconstruction was performed due to the absence of a Doppler signal over the
      pedal arteries after ligation of the common femoral artery. In two cases
      complications in the form of hemorrhage and repeated infection developed in the
      late postoperative period; in one case excision and ligation was performed, and
      in the last case reconstruction with a silver-impregnated dacron prosthesis. None
      of the patients required an amputation. Overall prognosis is uncertain because of
      the high incidence of postoperative drug injection despite aggressive drug
      rehabilitation.

PMID- 16817050
TI  - Use of mesh cerclage in prevention of early preterm delivery: a promising new
      surgical method for women with dilated cervix and membrane herniation?
AB  - OBJECTIVE: To present our innovative surgical method for prevention of early
      preterm delivery in women with cervical dilatation and membrane herniation. STUDY
      DESIGN: A woman in the 24th gestational week, with membrane herniation due to a 2
      3 cm dilatation of the cervix, is presented. The surgical technique for occlusion
      and reinforcement of the dilated cervix with circular suture and polypropylene
      mesh is described. RESULTS: We succeeded in preventing early preterm delivery and
      achieving 38 gestational weeks when the mesh cerclage was electively removed.
      CONCLUSIONS: Occlusion of the dilated cervix by mesh cerclage is a promising new
      surgical possibility of preventing early preterm delivery and achieving fetal
      maturity in women with dilated cervix and membrane herniation.

PMID- 16817051
TI  - Endovascular treatment of a direct post-traumatic carotid-cavernous fistula with
      electrolytically detachable coils.
AB  - Carotid-cavernous fistulae are abnormal communications between the internal
      carotid artery and venous compartments of the cavernous sinus. Fistulae are
      uncommon but well-documented sequelae of craniofacial trauma. The characteristic
      clinical presentation includes ocular pain, chemosis, exophthalmus and visual
      disturbances. We report on a 28-year-old man with a history of severe
      craniocerebral injury, including multiple craniofacial fractures resulting from a
      fall from a height of approximately 6 meters, who was surgically treated one year
      ago. Two months before presentation, the patient began to exhibit progressive
      chemosis, proptosis, eyelid swelling, diplopia and exophthalmus. Computerized
      tomography and computerized tomographic angiography revealed findings consistent
      with a carotid-cavernous fistula of the right side of the cavernous sinus with
      dilatation of the right ocular vein. Digital subtractional angiography of the
      right internal carotid artery revealed a fistula between the cavernous part of
      the artery and the right cavernous sinus. There was only minimal blood flow in
      the supraclinoid part of the internal carotid artery because of the high pressure
      within the fistula. Our decision was to try to occlude the fistula by means of
      endovascular embolization. The origin of the fistula in the internal carotid
      artery was successfully obliterated with seven electolytically detachable coils.
      Control digital subtractional angiography at the end of the procedure
      demonstrated minimal residual flow through the fistula. Two months after the
      treatment, angiographic control revealed complete obliteration of the fistula.
      Clinical examination showed total resolution of signs and symptoms of a carotid
      cavernous fistula. Endovascular transarterial embolization of carotid cavernous
      fistulae is a widely accepted, safe and successful treatment option. In the case
      that we describe we occluded the fistula and right cavernous sinus with
      electrolytically detachable coils that we could place into the sinus. Other
      endovascular treatment options include the use of detachable balloons, stent
      placement, transvenous embolization or surgical ligation of the fistula.

PMID- 16817052
TI  - Different approaches to surgical treatment of arachnoid cysts.
AB  - Although most arachnoid cysts remain static fluid-filled compartments throughout
      life, some become enlarged, exerting a mass effect on adjacent neural structures.
      The decision-making process for patients with arachnoid cysts still represents a
      challenge for the neurosurgeon. We report three cases of intracranial arachnoid
      cysts treated with different surgical approaches: (i) endoscopic fenestration of
      the cyst into the lateral ventricle; (ii) a cystoperitoneal shunt; (iii) a
      cystoperitoneal shunt and establishment of communication between the cyst and the
      fourth ventricle with the help of an endoscope. Given the advances in
      instrumentation over the past decade, it is probable that most arachnoid cysts
      will be managed endoscopically in the future.

PMID- 16817053
TI  - Distinct immunohistochemical expression of osteopontin in the adult rat major
      salivary glands.
AB  - Osteopontin is a multifunctional protein secreted by epithelial cells of various
      tissues. Its expression in the adult rat major salivary glands has not yet been
      studied. We examined osteopontin expression by immunohistochemistry using a well
      characterized monoclonal antibody. Submandibular glands of young adult male rats
      (70-100 days old) showed specific expression in secretion granules of granular
      duct cells but also in cells of the striated ducts and excretory duct. In the
      major sublingual as well as the parotid gland expression was found solely in the
      duct system. In addition, a few interstitial-like cells exhibiting very strong
      immunostaining for osteopontin could be found in either organ. Expression could
      neither be seen in acinar cells nor in cells of the intercalated ducts. Moreover,
      in submandibular glands of more aged rats (6- to 7-month old) which show well
      developed granular convoluted tubules, there was almost exclusive expression of
      osteopontin in granular duct cells as well as in some interstitial-like cells,
      but barely in the striated/excretory duct system. Western blot analysis of the
      submandibular gland showed a specific band migrating at approximately 74 kDa,
      detectable at both age stages. Osteopontin secreted fom granular duct cells may
      influence the composition of the saliva, e.g. thereby modulating pathways
      affecting sialolithiasis. Its expression in striated duct cells may also hint to
      roles such as cell-cell attachment or cell differentiation. The cell-specific
      expression detected in the rat major salivary glands differs in part from that
      reported in mice, human and monkey.

PMID- 16817054
TI  - Chronic paroxysmal hemicrania, hemicrania continua and SUNCT: the fate of the
      three first described cases.
AB  - The first patient with chronic paroxysmal hemicrania has been followed for 45
      years, and for 33 years with indomethacin treatment. The headache became less
      severe with time; there was no indomethacin tachyphylaxis. The first patient with
      SUNCT was followed for 28 years, until his demise at 89. Pain became worse with
      time. No adequate therapy was found. The first patient with Hemicrania continua
      was followed for 19 years, until her demise at 81. She was treated with
      indomethacin during the whole observation time. There was no tachyphylaxis. Both
      patients treated with indomethacin developed gastric ulcer. And both had gastric
      surgery. Indomethacin therapy may be a life-long affair. The risk of gastric
      complications may be substantial.

PMID- 16817055
TI  - Public health support to policies in the fields of headache. Different ways of
      producing data and modalities of reading them with the aid of the meta-analytic
      approach.

PMID- 16817056
TI  - A theory-based approach to understanding sexual behavior at Mardi Gras.
AB  - Using the Triandis Model of Interpersonal Behavior (TIB), we considered the
      unique context of Mardi Gras, the annual festival in New Orleans, Louisiana, and
      how it might influence sexual behavior. This study utilized a two-stage,
      qualitative and quantitative methodological framework. Focus groups of past Mardi
      Gras participants were held to gather data to inform the development of the study
      instruments, and data were subsequently collected from 300 Mardi Gras
      participants in February 2004 using a pencil-and-paper questionnaire. For women,
      the TIB model did not significantly predict intentions to engage in sexual
      behavior at Mardi Gras. Cognitive beliefs and subjective social norms predicted
      intentions to engage in oral and vaginal sex among male participants. For men and
      women, peer sexual activity, intentions, and previous sexual experience predicted
      engaging in sexual behaviors at Mardi Gras. Situational conditions related to
      Mardi Gras culture predicted anal sex behavior. The TIB, as a guiding framework
      for the study, makes apparent the importance of cultural context when developing
      interventions related to sexuality that are to be implemented in a specific
      setting like Mardi Gras.

PMID- 16817057
TI  - Examining links between cocaine use and street-based sex work in New South Wales,
      Australia.
AB  - We examined potential links between cocaine use and street-based sex work in New
      South Wales (NSW), Australia, following reports of increased cocaine use among
      injection drug users (IDU). Police data on prostitution and possession/use of
      cocaine was analysed using time series analysis. Interviews with key informants
      and IDU were also conducted, and data on cocaine use from ongoing monitoring
      systems targeted at IDU were analysed. There was a clear increase in cocaine use
      among IDU which occurred in 2001. This occurred at the same time as an increase
      in prostitution offenses. Qualitative data suggested that a greater number of
      primary heroin users were engaging in street-based sex work, which was driven in
      part by the increases in cocaine use among this group. Subsequent reductions in
      cocaine availability led to decreased cocaine use and possession offenses, along
      with reductions in prostitution offenses.

PMID- 16817058
TI  - Race, ethnicity, gender, and generational factors associated with the coming-out
      process among lesbian, and bisexual individuals.
AB  - Age at coming out among gay/lesbian/bisexual (GLB) persons and sexual debut with
      same-gendered partners has typically been investigated in samples that do not
      reflect the racial and ethnic diversity of these communities. Addressing this
      limitation, data were collected from a diverse sample of men and women attending
      large-scale GLB community events in New York and Los Angeles in 2003 (N = 2,733).
      Compared to older cohorts, younger cohorts (18-24 year olds) of both men and
      women reported significantly earlier ages for sexual debut with same-gendered
      partners, and earlier ages for coming out to themselves and to others. Also,
      women began the process at later ages than men, as they reported coming out to
      themselves and sexual debut with a same-gender partner approximately two years
      later than men. There were no racial or ethnic differences in age out to self or
      others; however, persons of color were less likely to be out to their parents.
      Service providers, sexuality educators, and researchers should attend to the
      diversity in experience of coming out among GLB populations as they relate to the
      individuals gender, age, and racial and ethnic backgrounds.

PMID- 16817059
TI  - Attitudes toward homosexuality among U.S. residents of Mexican descent.
AB  - This study examined attitudes toward lesbians and gay men in a sample of northern
      California residents of Mexican descent (N = 616), using 3-item versions of the
      Attitudes Toward Gay Men (ATG) and Attitudes Toward Lesbians (ATL) scales
      presented simultaneously in Spanish and English. Males attitudes toward
      homosexual men were significantly more negative than females attitudes, whereas
      females expressed relatively negative attitudes toward lesbians. Overall,
      respondents expressing negative attitudes endorsed more traditional gender
      attitudes than respondents with positive attitudes, tended to be older and less
      educated, had more children, were more likely to belong to a fundamentalist
      religious denomination and to attend religious services frequently, were more
      conservative politically, and were less likely to have personal contact with gay
      people. Further analyses revealed that associations between attitudes and
      education, number of children, personal contact, and religious attendance
      occurred mainly among respondents who spoke and read English (rather than
      Spanish) or identified with U.S. culture (rather than Mexican culture).

PMID- 16817060
TI  - The relationship between negative mood and sexuality in heterosexual college
      woman and men.
AB  - Negative mood states, such as depression and anxiety, are typically associated
      with decreased sexual interest and arousal. However, there is also some evidence
      that depressed or anxious mood may increase sexual interest or arousal in some
      individuals. In this study, 663 female college students (mean age = 18.9 years,
      SD = 1.21) answered questions regarding the effects of anxious and depressed mood
      on sexual interest and arousal and completed trait measures of sexual excitation
      and inhibition, anxiety, and depression. The majority of women reported decreased
      sexual interest and response when feeling depressed or anxious; a minority (about
      10%) of women, however, reported increased sexual interest/response during
      anxious and depressed mood. This sample of women was compared to a sample of 399
      college-aged men. In general, men were more likely than women to report increased
      sexual interest during negative mood states. Of the variables explored,
      propensity for sexual excitation was the strongest predictor of the relationship
      between negative mood and sexuality in women. Individual differences in the
      effects of negative mood may prove relevant to our understanding of a variety of
      topics, including risky and compulsive sexual behavior and sexual dysfunction.

PMID- 16817061
TI  - The ebb and flow of marital lust: a relational approach.
AB  - This diary study examined daily fluctuation in marital lust over a 56-day period.
      The purposes of the study were to describe typical patterns of lust over time and
      to examine intrapersonal and interpersonal associations between relationship
      affect, relationship states, and marital lust. We also tested various daily
      moderational predictions. Four patterns of daily fluctuation in lust were
      identified. Typical patterns varied from almost no fluctuation to wide
      fluctuation over time. Our findings showed that daily affect was generally
      related to lust both within partners and between partners. Also, spouses
      relational states (closeness and equality of power) moderated several of these
      intrapersonal and interpersonal associations. In general, the affect-lust link
      was strengthened by closeness and equality of power, while the lust-lust link
      between spouses was often conditioned by both relationship affect and relational
      states. However, the role of negative affect toward spouses in interactions with
      other constructs was not as expected. We discuss possible explanations for the
      findings and implications for further research.

PMID- 16817062
TI  - Non-erotic thoughts: content and relation to sexual functioning and sexual
      satisfaction.
AB  - We examined the possible range of content of non-erotic thoughts experienced
      during typical sexual activities with a partner. Undergraduate men (n = 47) and
      women (n = 50) were administered a measure of non-erotic thought content,
      frequency, and anxiety, along with measures of sexual attitude, satisfaction, and
      functioning. Men were more likely to report performance-related thoughts, and
      women were more likely to report thoughts about body image. However, men and
      women were equally likely to report thoughts about the external consequences of
      the activity (e.g., pregnancy, being caught) and the emotional consequences of
      the activity (e.g., morality, implications of the activity for the relationship).
      Women reported that their thoughts occurred more frequently and caused more
      anxiety. Greater thought frequency and greater anxiety over thoughts were
      associated with poorer sexual functioning for both men and women. For women,
      greater frequency of and anxiety evoked by thoughts was associated with lower
      sexual satisfaction. These data provide modest support for cognitive-behavioral
      models of sexual dysfunction and indicate the importance of both examining a
      broad range of non-erotic thought content and taking gender into account when
      applying these models to understanding and treating sexual difficulties.

PMID- 16817063
TI  - Gender differences in the enactment of sociosexuality: an examination of implicit
      social motives, sexual fantasies, coercive sexual attitudes, and aggressive
      sexual behavior.
AB  - An unrestricted sociosexual orientation (the endorsement of casual sex) has been
      found to correlate with undesirable behaviors and personality characteristics
      more so in men than in women. Using a community sample of men and women, we
      investigated the correlations between sociosexuality and behaviors, motives,
      attitudes, and fantasies related to sexual aggression. Participants (n = 168;
      ages 21-45) completed self-report measures of sociosexual orientation, sexual
      conservatism, rape myth acceptance, adversarial sexual beliefs, attitudes toward
      women, sexual behaviors, and perpetration of sexual aggression. Participants also
      wrote five brief stories that were scored for power and affiliation-intimacy
      motives and two sexual fantasies that were coded for the theme of dominance. For
      both men and women, an unrestricted sociosexual orientation was correlated with
      behavioral items indicating earlier life experiences with sex, a greater number
      of lifetime sex partners, and more frequent sexual activity. For men, an
      unrestricted sociosexual orientation was linked with higher levels of rape myth
      acceptance and adversarial sexual beliefs; more conservative attitudes toward
      women; higher levels of power motivation and lower levels of affiliation-intimacy
      motivation; and past use of sexual aggression. For women, an unrestricted
      sociosexual orientation was associated with sexual fantasies of dominance and
      lower levels of sexual conservatism.

PMID- 16817064
TI  - The sexual partnerships of people with serious mental illness.
AB  - We compared the sexualities of people with serious mental illness and the general
      population using the National Health and Social Life Survey (Laumann et al.,
      1994) and the Indiana Mental Health Services and HIV Risk Study (Wright, 2003).
      We investigated whether and how the sexual behaviors and relationships of people
      with serious mental illness differ from the general populations and identified
      factors differently influencing the organization of sexuality in these two
      groups. We found evidence that the relationships of people with serious mental
      illness are characterized by less intimacy and commitment than those of the
      general population. Additionally, although people with serious mental illness use
      condoms more consistently, they are also more likely to have concurrent
      relationships and tend to have sex sooner with new partners, which may contribute
      to a higher risk of contracting HIV. Our findings point to a need for a paradigm
      shift in the way that clinicians and researchers conceptualize and manage client
      sexuality. A less individualistic approach that takes into consideration the
      relationship context and social and institutional constraints is needed.

PMID- 16817065
TI  - Peep show establishments, police activity, public place, and time: a study of
      secondary effects in San Diego, California.
AB  - An empirical study was undertaken in San Diego, California, to test assumptions
      made by the government and by conservative religious policy advocates that there
      is a greater incidence of crime in the vicinity of peep show establishments. We
      asked two questions: (a) Is criminal activity in San Diego particularly acute at
      peep show establishments compared to surrounding control locations? and (b) Is
      criminal activity in San Diego disproportionately greater at or near peep show
      establishments between the hours of 2 a.m. and 6 a.m. compared to other times of
      the day? The levels of crime activity and the expenditure of police resources
      were examined by measuring the number of calls-for-service (CFSs) to the police
      within a 1,000-ft. area on either side of the peep show establishments and
      comparably-sized control areas beyond the immediate 1,000-foot area. A more
      focused late-night (2 a.m. to 6 a.m.) analysis was also undertaken. The results
      showed no reliable evidence of differences in crime levels between the control
      and test areas, nor was there any evidence of disproportionately greater amounts
      of crime within the 2 a.m. to 6 a.m. time period in the areas surrounding the
      peep show establishments. We concluded that San Diego does not have a problem
      with crime at the peep show establishments generally, nor is there a heightened
      problem with crime during the 2 a.m. to 6 a.m. period. We discuss the
      implications of assuming that peep show establishments are associated with
      negative effects in the community and the possibility of viewpoint discrimination
      against sex communication.

PMID- 16817066
TI  - Sexual functioning in women with chronic pelvic pain: the impact of depression,
      support, and abuse.
AB  - Many studies have documented associations between sexual functioning, depression,
      experiences of childhood sexual abuse, relationship support, and chronic pelvic
      pain, but none have addressed the interrelationships among all of these variables
      in a unified model. The aim of this preliminary study was to construct an
      integrative model predicting sexual functioning for women with chronic pelvic
      pain. Sixty-three women with chronic pelvic pain completed measures of sexual
      functioning for use as the criterion variable, and measures of the impact of
      chronic pain, depression, experiences of sexual abuse, and relationship support
      as predictors. The primary finding was that depression mediated the effects of
      child sexual abuse and partially mediated the effects of relationship support on
      sexual behavior and satisfaction with the sexual relationship. In addition to its
      indirect relationship through depression, relationship support also independently
      predicted sexual function. Thus, in this nonclinical sample, the effects of child
      sexual abuse on sexual function depended on the extent of depressive symptoms,
      while the influence of relationship support depended in part on depression.

PMID- 16817067
TI  - Sexual identity development among gay, lesbian, and bisexual youths: consistency
      and change over time.
AB  - A longitudinal report of 156 gay, lesbian, and bisexual youths examined changes
      in sexual identity over time. Fifty-seven percent of the youths remained
      consistently self-identified as gay/lesbian, 18% transited from bisexual to
      gay/lesbian, and 15% consistently identified as bisexual over time. Although
      youths who consistently identified as gay/lesbian did not differ from other
      youths on time since experiencing sexual developmental milestones, they reported
      current sexual orientation and sexual behaviors that were more same-sex centered
      and they scored higher on aspects of the identity integration process (e.g., more
      certain, comfortable, and accepting of their same-sex sexuality, more involved in
      gay-related social activities, more possessing of positive attitudes toward
      homosexuality, and more comfortable with others knowing about their sexuality)
      than youths who transited to a gay/lesbian identity and youths who consistently
      identified as bisexual. Contrary to the hypothesis that females are more sexually
      fluid than males, female youths were less likely to change identities than male
      youths. The finding that youths who transited to a gay/lesbian identity differed
      from consistently gay/lesbian youths suggests that identity integration continues
      after the adoption of a gay/lesbian sexual identity.

PMID- 16817068
TI  - Gender differences in the content of cognitive distraction during sex.
AB  - This study compared 220 college men and 237 college women on two types of self
      reported cognitive distraction during sex, performance- and appearance-based.
      Affect, psychological distress, sexual knowledge, attitudes, fantasies,
      experiences, body image, satisfaction, and sexual function were assessed with the
      Derogatis Sexual Functioning Inventory and the Sexual History Form to determine
      associations with distraction. Between-gender analyses revealed that women
      reported higher levels of overall and appearance-based distraction than did men,
      but similar levels of performance-based distraction. Within-gender analyses
      revealed that women reported as much of one type of distraction as the other,
      while men reported more performance- than appearance-based distraction. In women,
      appearance-based distraction was predicted by negative body image, psychological
      distress, and not being in a relationship, while performance-based distraction
      was predicted by negative body image, psychological distress, and sexual
      dissatisfaction. In men, appearance-based distraction was predicted by negative
      body image, sexual dissatisfaction and not being in a relationship, while
      performance-based distraction was predicted by negative body image and sexual
      dissatisfaction. Investigating the content of cognitive distraction may be useful
      in understanding gender differences in sexual experience and in refining
      cognitive components of sex therapy.

PMID- 16817069
TI  - Dysfunctional sexual beliefs as vulnerability factors to sexual dysfunction.
AB  - The differences on sexual beliefs presented by men and women with sexual
      dysfunction and their sexually functional counterparts were investigated. A total
      of 488 participants (160 females and 232 males without sexual problems and 47
      females and 49 males with a DSM-IV diagnosis of sexual dysfunction) answered the
      Sexual Dysfunctional Beliefs Questionnaire. Findings showed that, although
      effects have only reached statistical significance for the female group, both
      dysfunctional men and women endorsed more sexual dysfunctional beliefs than
      functional. Women presented significantly more age related beliefs (after
      menopause women loose their sexual desire, as women age, the pleasure they get
      from sex decreases) and body image beliefs (women who are not physically
      attractive cannot be sexually satisfied). Additionally, sexually dysfunctional
      males presented higher scores (not statistically significant) on 'macho' belief
      (a real man has sexual intercourse very often) and the beliefs about women
      satisfaction (the quality of the erection is what most satisfies women). Overall,
      findings support the idea that sexual beliefs may play a role as vulnerability
      factors for sexual dysfunction.

PMID- 16817070
TI  - The brief sexual attitudes scale.
AB  - The measurement of sexual attitudes is important, and ease of scale usability is
      one key aspect of measurement. This paper details three studies conducted to
      develop a briefer and thus more efficient version of the multidimensional Sexual
      Attitudes Scale (43 items). The first two studies (I and II) employed existing
      data sets to develop a 23-item version of the Sexual Attitudes Scale, using
      exploratory factor analysis in Study I and confirmatory factor analysis in Study
      II. The same four subscales of Permissiveness, Birth Control (formerly called
      Sexual Practices), Communion, and Instrumentality were retained in the 23-item
      measure, called the Brief Sexual Attitudes Scale. Study III was a prospective
      data collection using only the 23 items composing the Brief Sexual Attitudes
      Scale. The four subscales were hypothesized to correlate with a number of
      relationship measures in predictable ways. Results indicated that the Brief
      Sexual Attitudes Scale is a reliable and valid measure of the four sexual
      attitudes, and has strong psychometric properties. It should be effective and
      efficient for both research and clinical uses.

PMID- 16817071
TI  - Perceptions of sexual coercion in heterosexual dating relationships: the role of
      aggressor gender and tactics.
AB  - A large body of research has found a concerning prevalence rate of sexual
      coercion in heterosexual college student dating relationships; however, little
      research has examined how college students perceive and interpret these
      behaviors. In the current study we examined the impact of initiator gender and
      sexually coercive strategy (verbal pressure, purposeful intoxication, physical
      force, or control/mutual consent) on perceptions of the aggressor, victim,
      behavior, and relationship quality. Results indicated that men who coerce are
      viewed as aggressive; women who coerce are viewed as promiscuous. Targets of
      sexual coercion are not perceived as experiencing high levels of victimization
      following the incident. These findings suggest that college students do not
      perceive sexually coercive behaviors to be highly problematic. The results are
      discussed in terms of gender roles and practical implications for college student
      relationships.

PMID- 16817072
TI  - Prognosis of women with pelvic pain during pregnancy: a long-term follow-up
      study.
AB  - STUDY DESIGN: A follow-up study of women with pelvic pain during pregnancy.
      OBJECTIVES: To evaluate prognostic factors for pelvic pain. METHODS: Out of a
      cohort of 870 pelvic pain patients, 598 women, who delivered less than 42 months
      prior to the follow-up measurement, were selected for follow-up. RESULTS: Data of
      430 women were available for analysis with a mean follow-up duration of 18 months
      postpartum. Forty-three women still experienced moderate or severe pain and were
      seriously hindered in more than one activity. At intake symptomatic women
      experienced a higher overall severity of complaints, more walking deficiencies,
      and mentioned prepregnancy back pain more often and reported labor lasting longer
      than 18 h 2.5 times more often than asymptomatic women. Explained variance of
      these factors is small. CONCLUSIONS: Mean 18 months postpartum a small group had
      moderate or severe pain. Prepregnancy back pain, severity of complaints, and
      number of walking deficiencies at primary referral as well as duration of labor
      showed a significant relation with symptoms.

PMID- 16817073
TI  - The joint effect of vaginal Ureaplasma urealyticum and bacterial vaginosis on
      adverse pregnancy outcomes.
AB  - OBJECTIVE: To examine associations of vaginal Ureaplasma urealyticum (UU) and
      bacterial vaginosis (BV) with preterm delivery (PTD), small for gestational age
      (SGA), and low birth weight (LBW). MATERIAL AND METHODS: A population-based,
      prospective cohort study of 2,927 pregnancies. After exclusion of multiples and
      antibiotic use sample size was 2,662. BV (Amsel's criteria) and UU (culture) were
      assessed in week 17. Gestational age was determined by last menstrual period,
      confirmed by ultrasound measurement in 97.5%. SGA infants were calculated from
      intrauterine fetal growth measurements. RESULTS: There was no increased risk for
      spontaneous PTD among women with BV only (crude odds ratio 1.0, 95% CI 0.4-2.7),
      among women with UU only (1.3, 0.8-2.0), nor among women with UU + BV (0.9, 0.4
      2.3) compared to women without UU and BV. However, there was a threefold
      increased risk of a LBW birth in women with UU + BV (3.1, 1.8-5.4), a twofold
      risk of a LBW birth among women with UU only (1.9, 1.3-2.9), but no increased
      risk among women with BV only (0.8, 0.3-2.2). Similarly, women with UU + BV had
      over a twofold increased risk of an SGA birth (2.3, 1.3-4.0), women with UU only
      had a 70% increase (1.7, 1.1-2.5), whereas a nonsignificant increase was found in
      women with BV only (1.3, 0.6-2.9). Adjustment by established confounders
      (smoking, previous PTD, previous LBW, and Escherichia coli) did not affect risk
      estimates. CONCLUSION: This analysis suggests that UU is independently associated
      with fetal growth and LBW and that BV with UU may enhance the risk of these
      outcomes.

PMID- 16817074
TI  - The Pregnancy Mobility Index: a mobility scale during and after pregnancy.
AB  - BACKGROUND: During pregnancy, every second woman will experience some degree of
      back or pelvic pain. While several validated instruments to assess back pain
      exist for the general population, these are not suitable for application in a
      pregnant population and have not been validated for this purpose. A pregnant
      population not only differs from the general population regarding the type of
      back pain--frequently a pelvic girdle component is added--but pregnant women also
      have different mobility patterns and expectations. We therefore present in this
      study a self-report mobility scale specifically designed for a pregnant
      population: the Pregnancy Mobility Index. METHODS: Longitudinal cohort study
      including 672 nulliparous women with a singleton low-risk pregnancy. The
      Pregnancy Mobility Index consists of items concerning day-to-day activities
      selected through literature research and clinical experience. Participating women
      completed the questionnaire at 12 and 36 weeks' gestation and one year after
      delivery. Reliability, construct and criterion validity were tested. RESULTS: The
      internal consistency (Cronbach's alpha) was 0.8 or higher. The Pregnancy Mobility
      Index scales correlated best with the physical and pain scale of the RAND-36,
      indicating a good construct validity. The assumptions that the Pregnancy Mobility
      Index scores increase during pregnancy and decrease after delivery and that women
      with back or pelvic problems scored higher on the Pregnancy Mobility Index
      domains than women without back or pelvic pain were confirmed, indicating a good
      criterion validation. CONCLUSION: The Pregnancy Mobility Index has been shown to
      be a reliable and valid questionnaire well suited for use during and after
      pregnancy.

PMID- 16817075
TI  - Fetal heart rate patterns and neurodevelopmental outcome in very low birth weight
      infants.
AB  - BACKGROUND: To evaluate the validity of fetal heart rate monitoring during the
      last hour prior to birth, as a predictor of long term neurodevelopmental outcome
      of very low birth weight infants. METHODS: A total of 111 very low birth weight
      infants were included in the study. Fetal heart rate tracings were obtained
      during the last hour prior to delivery. A perinatologist, blinded to the neonatal
      outcome, evaluated the tracings and divided them into three groups: reassuring,
      nonreassuring, and pathological. Neurodevelopmental status was evaluated at age 2
      years. The relationship between fetal heart rate monitoring results and the
      neurodevelopmental outcome at 2 years of age was assessed with a chi-square test
      and the Student's t-test. RESULTS: At 2 years of age 97 (87.4%) of the children
      had normal neurodevelopmental function, while 14 (12.6%) had variable degrees of
      neurodevelopmental impairment. The fetal heart rate monitoring results were
      classified as reassuring (normal) in 35 cases (31.5%), nonreassuring in 56 cases
      (50.5%), and pathological in 20 cases (18.0%). Both normal and pathological fetal
      heart rate patterns were associated with similar incidence of abnormal
      neurodevelopmental outcome, 14.3% and 15.0% of cases, respectively (p=0.778).
      Pathological fetal heart rate patterns as a predictor of neurodevelopmental
      outcome had a sensitivity of 27%, specificity of 74%, positive predictive value
      of 15%, and negative predictive value of 86%. CONCLUSION: Electronic fetal heart
      rate monitoring prior to delivery is not a reliable tool for the prediction of
      neurodevelopmental impairment in premature infants of very low birth weight, at 2
      years of age.

PMID- 16817076
TI  - Audit of severe maternal morbidity in Uganda--implications for quality of
      obstetric care.
AB  - BACKGROUND: For every maternal death, there are probably 100 or more morbidities,
      but the quality of health care for these women who survive has rarely been an
      issue. The purpose of this study is to explore audit of severe obstetric
      morbidity and the concept of near miss in four referral hospitals in Uganda.
      METHODS: This was an exploratory systematic enquiry into the care of a subset of
      women with severe morbidity designated as near miss cases by organ failure or
      dysfunction. Patient factors and environmental factors were also explored. Data
      were abstracted from clinical records and from interviews with patients,
      relatives, and health workers. RESULTS: Records of 685 women with severe maternal
      morbidity were examined and 229 cases fulfilled the criteria for near miss cases.
      Obstetric hemorrhage, rupture of the uterus, puerperal sepsis, and abortion
      complications were the major conditions leading to the near miss state in more
      than three quarters of the patients. Nearly half the cases were at home when the
      events occurred. More than half the cases delayed to seek care, because the
      patients were unwilling, or relatives were not helpful. Similar proportion also
      experienced substandard care in the hospitals. CONCLUSIONS: A systemic analysis
      found substandard care and records, and patient-related factors in more than half
      the cases of severe maternal morbidity. Audit of near miss cases might offer a
      non-threatening stimulus for improving the quality of obstetric care.

PMID- 16817077
TI  - Obstetric outcome in post-term pregnancies: time for reappraisal in clinical
      management.
AB  - BACKGROUND: The objective of this study was to determine the outcome of pregnancy
      in post-term cases compared with term cases in a well defined population
      receiving modern obstetric care. METHODS: We utilized the population-based birth
      registry data of the Kuopio University Hospital (1990-2000) to investigate
      pregnancy outcome in 1,678 post-term singleton pregnancies. The general obstetric
      population (n=22,712) was used as a reference group in logistic regression
      analysis. RESULTS: The overall frequency of post-term pregnancies was 6.9% and
      the incidence of post-term pregnancies was found to be increased in obese,
      primiparous, and smoking women, whereas in women with chronic diseases and
      obstetric risks deliveries were induced earlier. The risks of macrosomia,
      maternal complications, and operative deliveries were increased in post-term
      pregnancies. Post-term infants experienced meconium passage (21.2% versus 12.8%)
      (p<0.01) and intrapartum asphyxia (3.4% versus 2.1%) (p<0.01) significantly more
      often than the controls. However, the stillbirth rate was low, probably due to
      careful monitoring of these pregnancies. CONCLUSIONS: Although high-risk
      pregnancies were not allowed to come post-term, postmaturity per se is a moderate
      risk state compromising fetal well-being with regard to meconium passage and acid
      base status at birth. We conclude that simple antenatal monitoring beyond 42
      weeks reduces perinatal mortality but is inefficient in reducing meconium-stained
      liquor seen with increasing gestation.

PMID- 16817078
TI  - Obstetrical factors related to nuchal cord.
AB  - BACKGROUND: To investigate the intrapartum factors related to umbilical cord
      nuchal loops (nuchal cord) with particular reference to shoulder dystocia.
      METHODS: We studied all singleton pregnancies with a vertex presentation and a
      birth weight of at least 2500 g from 1 January 1978 to 31 March 1997 and the
      13,717 pregnancies with nuchal cord were compared to the 44,136 without nuchal
      cord. RESULTS: When compared to pregnant women without nuchal cord, a greater
      proportion of pregnant women with nuchal cord underwent induction of labor
      (adjusted OR 1.09, 95% CI 1.04-1.15) and augmentation with oxytocin (adjusted OR
      1.06, 95% CI 1.01-1.11). They had a longer second stage of labor (p=0.0013) and a
      greater proportion of primiparous women with tight nuchal cord had second stage
      of labor that lasted longer than two hours (adjusted OR 1.21, 95% CI 1.03-1.41).
      The proportion of abnormal fetal heart rate patterns was higher in the presence
      of nuchal cord (adjusted OR 1.61, 95% CI 1.55-1.68). Shoulder dystocia occurred
      more commonly in association with nuchal cord, especially when the nuchal cord
      was tight (adjusted OR 1.50, 95% CI 1.30-1.72 for all nuchal cord; adjusted OR
      1.82, 95% CI 1.42-2.34 for tight nuchal cord). CONCLUSIONS: Umbilical cord nuchal
      loops are associated with induction of labor, slow progress of labor, and
      shoulder dystocia.

PMID- 16817079
TI  - Angiographic embolization for obstetrical hemorrhage: effectiveness and follow-up
      outcome of fertility.
AB  - BACKGROUND: This study was undertaken to describe the results of angiographic
      embolization for obstetrical hemorrhage and the follow-up outcome of fertility.
      METHODS: Consecutive patients who received angiographic embolization for the
      management of obstetrical hemorrhage at a single tertiary center were included in
      this study. Medical records were reviewed to collect the clinical data and
      details on the procedure. Patients were interviewed by telephone to obtain the
      long-term outcomes for complications, menstruation, desire for conception, and
      subsequent pregnancies. RESULTS: Embolization was successful in 42 (86%) of 49
      patients with obstetrical hemorrhage resulting from various causes. The main
      cause of hemorrhage was uterine atony (n=24). The success rate was significantly
      lower in cases with abnormal placentation than in other causes of hemorrhage
      (p<0.05). The procedure took an average of 45.6 min (range, 20-120 min). There
      were no major complications related to the procedure. We were able to follow-up
      48 patients. Among 37 patients with preserved uteri, menstruation resumed
      spontaneously in 36 patients. Nine patients became pregnant, of which six gave
      birth to healthy babies and three ended in early miscarriage. CONCLUSIONS:
      Angiographic embolization is an effective noninvasive method for the management
      of obstetrical hemorrhage and a useful technique for preserving fertility.

PMID- 16817080
TI  - A narrow pelvic outlet increases the risk for emergency cesarean section.
AB  - BACKGROUND: The rate of cesarean section (CS) is increasing in Sweden as well as
      in most of the industrialized world. One of the most common indications for
      emergency CS is protracted labor. To what extent fetal pelvic disproportion is a
      cause of protracted labor is unclear. The value of pelvimetry has been
      questioned. The purpose of this study was to investigate whether women delivered
      with emergency CS because of protracted labor had a narrower pelvis than women
      delivered vaginally did. METHODS: Thirty women delivered with CS because of
      protracted labor comprised the study group. Thirty women vaginally delivered
      served as controls. The two groups were matched for gestational age, birth
      weight, and parity. The study group and the control group underwent an X-ray
      pelvimetry within 1 month of delivery. RESULTS: The study group and the control
      group did not differ in maternal age or body mass index. The mean birth weight
      was 3914 g in the study group and 3884 g in the control group. The mean pelvic
      outlet was 328 mm in the study group and 346 mm in the control group (P=0.0024).
      The mean pelvic inlet was 245 mm in the study group and 255 mm in the control
      group (P=0.0038). CONCLUSION: A narrow pelvic outlet is associated with an
      increased risk of emergency CS because of protracted labor. A postpartum
      pelvimetry is recommended and should be used when to decide on route of delivery
      in forthcoming pregnancies.

PMID- 16817081
TI  - Randomized study on the effect of adding oxytocin to ethacridine lactate or
      misoprostol for second-trimester termination of pregnancy.
AB  - OBJECTIVE: To compare effectiveness of misoprostol and ethacridine lactate with
      or without oxytocin in second-trimester medical abortions. SUBJECTS AND METHODS:
      A randomized prospective study. A total of 388 women with genetic indications for
      termination of pregnancy at 13-24 weeks of gestation were recruited. Group I
      (n=85) were treated with extra-amniotic ethacridine lactate, 10 ml instilled per
      gestational week, to a maximum of 200 ml. Group II (n=93) were treated with
      misoprostol administered intravaginally (200 microg), followed by 100 microg of
      oral misoprostol 4 hourly for 24 h. Group III (n=102) were treated with a
      combination of ethacrine lactate and oxytocin. An initial dose of 6 mU/min
      oxytocin was given, followed by additional 6 mU/min doses every 20 min. Group IV
      (n=96) were treated with a combination of misoprostol and oxytocin administered
      in a similar way as in group III. The main outcome measures were time to induce
      abortion, side effects, and failure/success rates. RESULTS: The mean time to
      induce abortion was 14.2+/-3.6, 13.2+/-3.4, 10.8+/-2.6, and 9.9+/-2.4 h in groups
      I, II, III, and IV, respectively (p<0.001). Addition of oxytocin to ethacridine
      lactate did not decrease the risk of prolongation of induction beyond 24 h but
      use of oxytocin with misoprostol did reduce the risk of induction beyond 24 h
      (OR: 0.46, 95%CI: 0.21-1, p<0.05). The occurrence of minor side effects was
      similar in all groups. CONCLUSION: Addition of oxytocin to ethacridine lactate or
      misoprostol significantly decreases the length of time to induce abortion without
      supplementary side effects.

PMID- 16817082
TI  - Female patients report on health care staff's disobedience of ethical principles.
AB  - BACKGROUND: Earlier studies have shown a high prevalence of abuse in health care
      (AHC). We hypothesized that patients might easily feel abused when staff do not
      follow prevailing ethical principles. Therefore we developed the Violations of
      Ethical Principles Questionnaire (ViolEP), with 30 examples of situations in
      health care where four ethical principles are disobeyed (autonomy,
      nonmaleficence, justice, and integrity). Respondents reported whether or not they
      had ever experienced each of the situations, and whether or not they had
      perceived that event as a violation. RESEARCH QUESTIONS: 1. What proportion of
      female patients have ever experienced staff disobeying ethical principles in
      health care? 2. To what extent are such events perceived as violations? and 3.
      How well do perceived violations of ethical principles correspond to experiences
      of AHC? METHOD: Our sample was 661 consecutive female patients at the Department
      of Obstetrics and Gynecology in Linkoping, Sweden. They completed ViolEP and
      NorVold Abuse Questionnaire (NorAQ) at home and returned them by post. RESULTS:
      20/661 (64%) women answered the ViolEP and 426/661 (64%) returned the NorAQ. The
      majority (73%) (306/420) had experienced staff disobeying ethical principles.
      More than every second woman had perceived those events as violations (68%)
      (209/306). The prevalence of AHC was 23%. ViolEP had good sensitivity but low
      specificity when we used AHC according to NorAQ as the "gold standard".
      CONCLUSION: The majority of the patients had experienced health care staff
      disobeying prevailing ethical principles. These events were not always perceived
      as violations. The reason for this discrepancy needs to be explored.

PMID- 16817083
TI  - Use of pH/whiff test or QuickVue Advanced pH and Amines test for the diagnosis of
      bacterial vaginosis and prevention of postabortion pelvic inflammatory disease.
AB  - BACKGROUND: Untreated bacterial vaginosis (BV) is a risk factor for postabortion
      pelvic inflammatory disease (PID). METHODS: Eight hundred and eight women who
      requested therapeutic abortion were consecutively examined for the presence of
      BV, using either pH/whiff test or QuickVue Advanced pH and Amines test. All
      patients who tested positive to BV were treated with clindamycin or metronidazole
      prior to abortion. RESULTS: Based on the wet smear examination, the incidence of
      BV was 21.6%. Positive pH and whiff test had a sensitivity of 53%, specificity of
      98% and Kappa index 0.59 (n=239). Values for QuickVue Advanced pH and Amines test
      were 53%, 97%, and 0.58 respectively (n=508). The incidence of PID among all
      patients was 2.4% after pharmacological abortion and 4.9% after surgical
      abortion. Among the patients with microscopic presence of BV diagnosed positive
      by the pH/whiff test or QuickVue Advanced pH and Amines test and treated with
      antibiotics, no PID occurred. Patients with negative pH/whiff test or QuickVue pH
      and amines test who consequently did not receive preoperative antibiotics, but
      who later demonstrated microscopic presence of BV, had an incidence of 14.3%
      (5/35) postoperative PID compared to women with normal lactobacilli flora 4.3%
      (10/234) (OR 3.73; 95% CI 1.21-9.21). CONCLUSIONS: Although the pH/whiff test and
      QuickVue pH and Amines test failed to ascertain BV in almost half of the
      participants later found to have BV, we found that preabortal screening and
      subsequent treatment of those who test clinically positive does lower the
      incidence of postabortion PID.

PMID- 16817084
TI  - Effect of presurgical local infiltration of levobupivacaine in the surgical field
      on postsurgical wound pain in laparoscopic gynecological surgery.
AB  - BACKGROUND: To maintain a high standard of patient care, it is essential to
      provide adequate pain management in patients who undergo laparoscopic surgery.
      METHODS: We randomly enrolled 74 women who underwent laparoscopic surgery for
      gynecological benign diseases. Patients in the levobupivacaine group (n=37) were
      injected with 7 ml of 5 mg/ml levobupivacaine at all incisional areas patients in
      the control group (n=37) were injected with an equal volume of physiologic saline
      solution. In the postoperative period the following variables were assessed for
      each group: decline of hemoglobin concentration, consumption of analgesics, time
      of ambulation, length of postoperative ileus, length of postoperative hospital
      stay, and VAS scores at 6, 12, and 24 h after surgery. RESULTS: Mean pain
      intensity at 6 and 12 h after surgery was significantly lower in the
      levobupivacaine group than in the control group (p<0.01). Analgesic requirement
      was significantly lower (p<0.01) in the levobupivacaine group (0.3 phial+/-0.2)
      than in the control group (2.1 phial+/-1.0). The mean time of ambulation was
      significantly lower (p<0.05) in the levobupivacaine group (16+/-4) than in the
      control group (22+/-6). No significant difference was observed between the two
      groups in mean pain intensity 24 h after surgery, decline of hemoglobin
      concentration, length of postoperative ileus, or length of postoperative hospital
      stay. CONCLUSIONS: Our results suggest that presurgical infiltration of
      levobupivacaine in addition to general anesthesia and standard analgesic therapy
      significantly decreases the intensity of postsurgical pain, especially for the
      first 12 h after surgery, and reduces analgesic consumption after surgery.

PMID- 16817085
TI  - Placement of probes in electrostimulation and biofeedback training in pelvic
      floor dysfunction.
AB  - BACKGROUND: We examined the positioning of five commonly used probes in
      electrostimulation and biofeedback training. MATERIALS AND METHODS: Ultrasound
      and MRI were used to evaluate the position of these probes in two multiparous
      women, in reference to pelvic floor anatomy. RESULTS: From caudal to cranial we
      identified the anal external sphincter, puborectal muscle, and levator group.
      Positioning of probes varied considerably: the recording plates are situated from
      1 cm caudal to 6 cm cranial of the puborectal muscle. Most probes stretched, due
      to a relatively large diameter, the vagina wall, anal external sphincter, or
      puborectal muscle beyond physiological proportions. On straining, all probes were
      pushed upwards into the rectum. CONCLUSION: The positioning of all examined
      probes varied considerably. Hence it is not likely that these probes give a
      reliable and uniform registration of muscular activity of the pelvic floor
      function or are all optimal for electrostimulation.

PMID- 16817086
TI  - The role of mediolateral episiotomy during labour: analysis of risk factors for
      obstetric anal sphincter tears.
AB  - BACKGROUND: To determine risk factors for third-degree and complete third- or
      fourth-degree anal sphincter tears in vaginal delivery. METHODS: This is a
      retrospective comparative study. Fifty-three women who had sustained an anal
      sphincter tear were compared with 9,178 women without such a complication between
      August 1997 and October 2001. Obstetric data was collected from an electronic
      database. The main outcome measures were odds ratios. RESULTS: In the whole study
      population, odds ratios (ORs) for third-degree tears were: primiparity, 8.34 (95%
      confidence interval [CI] 3.98-17.48); vacuum extraction, 5.22 (95% CI 2.69
      10.13); parietal presentation, 3.97 (95% CI 1.16-13.64); and birth weight >4,000
      g, 3.77 (95% CI 2.11-6.68); and for complete third- or fourth-degree tears odds
      ratios were 5.42, 2.98, 5.64, and 3.01, respectively. In multivariate analysis,
      mediolateral episiotomy appeared to be protective as regards third-degree tears
      (OR 0.37 [95% CI 0.2020-0.70]). CONCLUSIONS: Vacuum-assisted vaginal delivery
      bears an increased risk of third-degree anal sphincter tears in a maternity unit
      where forceps are not used. Restricted use of mediolateral episiotomy may have a
      protective effect on the perineum.

PMID- 16817087
TI  - Polycystic ovary syndrome and metformin in pregnancy.
AB  - The diagnostic criteria of polycystic ovary syndrome incorporate
      hyperandrogenism, polycystic ovaries, anovulation and irregular menstrual
      bleeding and the syndrome is a recognized reason behind infertility. The
      biguanide metformin has encouraging effects on several metabolic aspects of the
      syndrome, including insulin sensitivity, plasma glucose concentration and lipid
      profile. Moreover, metformin improves the ovarian function in women diagnosed
      with polycystic ovary syndrome. Hence, metformin is considered an agent for
      ovulation induction among these patients. However, even higher ovulation
      frequencies have been observed when metformin has been adjuvant to clomifene
      therapy. Metformin-induced ovulation presumably brings about resumption of
      regular menstrual cycles and improved conception rates. Polycystic ovary syndrome
      patients are presumably more likely than healthy women to suffer from pregnancy
      related problems like early pregnancy loss, gestational diabetes mellitus and
      hypertensive states in pregnancy. Recent data suggest sparing effects of
      continued metformin therapy throughout pregnancy on early pregnancy loss and
      gestational diabetes mellitus, but its impact on hypertensive complications to
      pregnancy appears less evident. Instead, metformin might even induce pre
      eclampsia or exert no effect on blood pressure. CONCLUSION: So far, evidence for
      safety of continued therapy throughout gestation is insufficient, and existing
      papers are limited in design and might mask for fetal toxic outcomes due to
      metformin therapy. Prior to a recommendation of sustained metformin therapy
      throughout pregnancy, randomized placebo-controlled double-blinded clinical
      trials are awaited with interest, so that present assumptions on efficiency can
      be clarified, in order to assure efficient and safe management of pregnant
      polycystic ovary syndrome patients.

PMID- 16817088
TI  - Impaired glucose tolerance is associated with changes in clinical and biochemical
      parameters in women with polycystic ovary syndrome.
AB  - BACKGROUND: To characterize the phenotype of women with polycystic ovary syndrome
      with and without impaired glucose tolerance by determining various polycystic
      ovary syndrome-associated clinical and laboratory parameters. METHODS: In a
      prospective clinical study, we evaluated a series of 102 Caucasian women with
      polycystic ovary syndrome. Women completed a detailed questionnaire and underwent
      a standardized oral glucose tolerance test. Various polycystic ovary syndrome
      associated laboratory values such as hormonal and metabolic parameters were
      determined in these women and correlated to clinical data and the
      presence/absence of impaired glucose tolerance. Furthermore, the insulin
      resistance was calculated using the homeostasis model assessment index and
      correlated with clinical and biochemical parameters. RESULTS: Eighty-eight
      (86.3%) and 14 (13.7%) women were diagnosed as having non-impaired glucose
      tolerance and impaired glucose tolerance, respectively. Presence of impaired
      glucose tolerance was associated with an increased body mass index, increased
      body weight, elevated serum levels of bioavailable testosterone, insulin like
      growth factor-1, insulin, HbA1c, leucocytes, uric acid, alkaline phosphatase,
      hepatic C-reactive protein, and decreased serum levels of sex-hormone binding
      globulin. No association was ascertained with subfertility, hirsutism, and
      menstrual irregularities. We ascertained a positive correlation between the
      homeostasis model assessment index and body mass index, body weight, alkaline
      phosphatase, and hepatic C-reactive protein. CONCLUSIONS: Impaired glucose
      tolerance seems to be associated with a specific phenotype within polycystic
      ovary syndrome. This phenotype is more likely to present with biochemical
      parameters similar to an inflammatory reaction and a metabolic disorder.

PMID- 16817089
TI  - Transvaginal repair of enterocele and vaginal vault prolapse using autologous
      fascia lata graft.
AB  - BACKGROUND: The aim was to describe the operative technique of transvaginal
      repair of enterocele and apical prolapse using autologous fascia lata and report
      intra- and postoperative complications and long-term outcome. METHODS: A
      retrospective chart review of 74 consecutive patients who had repair of a
      symptomatic enterocele and vaginal vault prolapse or uterine prolapse from
      January 1987 to August 1999. All patients were followed for a minimum of 3 months
      and 61 were available for long-term evaluation at 18-106 months (median 52
      months). RESULTS: Intra- and postoperative complications were few. Pelvic
      examination at long-term follow-up disclosed a recurrence rate for enterocele of
      1.7%, vaginal vault prolapse of 8.3%, and cystocele of 15%. Ninety-one per cent
      were subjectively satisfied with the relief of mechanical vaginal symptoms. Only
      35% (6/17) were cured of constipation. Out of the 22 women who were sexually
      active after the procedure, 12 (54%) experienced improved quality. CONCLUSION:
      Repair of the posterior compartment defect and suspension of the vaginal vault
      using autologous fascia lata graft provides acceptable intra- and postoperative
      complication and long-term results.

PMID- 16817090
TI  - Vesicoamniotic shunting using a double-basket catheter appears effective in
      treating fetal bladder outlet obstruction.
AB  - BACKGROUND: To estimate the effect of vesicoamniotic shunting using a double
      basket catheter on treating fetal bladder outlet obstruction. METHODS: A
      retrospective study involving 8 prenatally diagnosed bladder outlet obstruction
      cases that underwent vesicoamniotic shunt placement using a double-basket
      catheter from 1998 to 2004. Patients were followed-up for prenatal and neonatal
      outcome analyses. RESULTS: Vesicoamniotic shunting was performed in 8 fetuses
      aged between 13.7 and 25.4 weeks' gestation (mean+/-SD, 19.7+/-3.5 weeks). Final
      diagnoses included 5 posterior urethral valves, 1 cloacal anomaly, 1 urethral
      stenosis, and 1 unknown. There were no maternal complications associated with the
      procedures. One woman diagnosed as having a fetus with posterior urethral valves
      decided to terminate her pregnancy and one fetus died in uterus spontaneously.
      Six women delivered live babies, and one baby required postnatal ventilatory
      support. Postnatal follow-up ranged from 3 to 60 months. Of the 6 newborns, 4
      survived with normal renal function, 1 had renal insufficiency, and 1 died of
      renal failure at 3 months of age. CONCLUSIONS: Vesicoamniotic shunt placement
      using a double-basket catheter may be effective in improving perinatal and
      neonatal outcomes through long-term decompression of the fetal urinary tract in
      carefully selected cases.

PMID- 16817091
TI  - Mutational analysis of the follistatin-related gene in women with premature
      ovarian failure and polycystic ovary syndrome.

PMID- 16817092
TI  - Polycythemia as a result of ectopic erythropoietin production in benign cystic
      leiomyoma of uterus.

PMID- 16817093
TI  - Salmonella Newport as the infective agent in a pyosalpinx.

PMID- 16817094
TI  - Brain metastases from early stage endometrial carcinoma 8 years after primary
      treatment: case report and review of the literature.

PMID- 16817095
TI  - The impact of physical activity in a case of polycystic ovary syndrome.

PMID- 16817096
TI  - When should blood samples be obtained for an appropriate estimation?

PMID- 16817099
TI  - [Finally under one umbrella -- the German Society on Eating Disorders was
      founded].

PMID- 16817100
TI  - [Pneumocystis jiroveci pneumonia in immunocompromised patients without AIDS -- a
      case series].
AB  - BACKGROUND AND OBJECTIVE: Patients with pneumonia resistant to treatment are a
      common problem in chest hospitals. Pneumocystis jiroveci (Pc) should always be
      considered as an opportunistic pathogen in case of potential, especially T cell
      related immunodeficiency, even if AIDS is not obvious. We report on cases of
      Pneumocystis jiroveci pneumonia (PcP) (n = 1921) without associated AIDS in a
      chest hospital. PATIENTS AND METHODS: We assessed 1921 inpatients presenting with
      pneumonia during January 1 (st) 1996 and September 30 (th) 2005 in our hospital.
      Identification of the cases with PcP was based on discharge diagnosis as well as
      on our microbiological database (detection of Pc by immunofluorescence-test (IFT)
      and/or PCR). RESULTS: The diagnosis of PcP was made in 14 patients (11 males, 3
      females) without associated AIDS. All patients were treated with
      immunosuppressive medication before admission. CD4 cell-counts were substantially
      decreased (CD4 cells < 200/microl) in 11 patients. To establish the diagnosis of
      PcP a Pc-PCR (using broncho-alveolar lavage (BAL) as the best material) was
      necessary in 8 patients, since the Pc-IFT proved positive only in 6 patients.
      Severe hypoxemia had to be managed by noninvasive ventilation in 3 patients,
      while another 4 patients had to be ventilated invasively. The mortality rate was
      2 out of 14 patients. CONCLUSIONS: PcP is an important disease in the
      differential diagnosis of pneumonia and at the same time constitutes a severe
      pulmonary complication in immunodeficient patients. If immunodeficiency is
      suspected, a CD4 cell-count as well as bronchoscopy with BAL should be performed
      to diagnose PcP. As expected, Pc-PCR was superior to Pc-IFT and should therefore
      be used on a routine basis for diagnosing PcP.

PMID- 16817101
TI  - [Leptospirosis after a stay in Thailand].
AB  - HISTORY AND ADMISSION FINDINGS: A 35-year-old man was admitted to our hospital
      with chills, headache, pain in the calves for five days and a bloody sputum. The
      day before he had returned from a 4-week trip to the north of Thailand. There he
      had participated in hiking trips and walked sometimes over wet fields with small
      skin injuries on his feet. The admission examination was uneventful except fever
      as high as 39 Celsius, particularly no rash, no conjunctivitis, no spleno- or
      hepatomegaly and no palpable lymph nodes could be noted. DIAGNOSTIC PROCEDURES:
      An x-ray of the chest showed confluent opacities, a bronchoscopy revealed diffuse
      alveolar hemorrhagy. Blood chemistry showed elevated liver enzymes, elevated
      kidney retention parameters and an increased C-reactive protein. An extended
      microbiological diagnostic procedure showed elevated antibody titers for
      leptospira and a PCR detected leptospira-DNA, representing acute leptospirosis.
      TREATMENT AND OUTCOME: After initiation of an antibiotic regimen including
      ceftriaxone and erythromycine the fever resolved immediately and the general
      condition improved. The patient could be discharged after two weeks in a good
      physical condition. CONCLUSION: The constellation of flu-like symptoms, hepatitis
      and nephritis, eventually escorted by bloody sputum, may suggest leptospirosis.

PMID- 16817103
TI  - [Cardiopulmonary resuscitation in adults].

PMID- 16817104
TI  - [Focal segmental glomerulosclerosis (FSGS). Molecular defects and clinical
      relevance].

PMID- 16817105
TI  - [Molecular and cellular basis of joint destruction in rheumatoid arthritis].

PMID- 16817106
TI  - [Where is acupuncture going? Letter no. 2].

PMID- 16817107
TI  - [Where is acupuncture going? Letter no.1].

PMID- 16817110
TI  - [Radiologic findings in hemochromatosis].

PMID- 16817121
TI  - [Evidence-based radiology: a new approach to evaluate the clinical practice of
      radiology].
AB  - Over the last several years, the concept and methodology of Evidence-Based
      Medicine (EBM) have received significant attention in the scientific community.
      However, compared to therapeutic medical disciplines, EBM-based radiological
      publications are still underrepresented. This article summarizes the principles
      of EBM and discusses the possibilities of their application in radiology. The
      presented topics include the critical appraisal of studies on the basis on EBM
      principles, the explanation of EBM-relevant statistical outcome parameters (e.
      g., "likelihood ratio" for diagnostic and "number needed to treat" for
      interventional procedures), as well as the problems facing evidence-based
      radiology. Evidence-based evaluation of radiological procedures does not only
      address aspects of cost-effectiveness, but is also particularly helpful in
      identifying patient-specific usefulness. Therefore it should become an integral
      part of radiologist training.

PMID- 16817122
TI  - [Familial breast cancer: what the radiologist needs to know].
AB  - About 10 % of breast cancers are "hereditary", i. e. caused by a pathogenic
      mutation in one of the "breast and ovarian cancer susceptibility genes" (BRCA).
      The BRCA genes 1 and 2 identified to date follow an autosomal dominant
      inheritance pattern. A clustering of breast cancer in a family without a
      documented mutation and without a recognizable inheritance pattern is usually
      referred to as "familial cancer". A distinction between hereditary and familial
      is difficult in the individual case because not all of the genetic mutations that
      cause breast cancer susceptibility are known and thus amenable to genetic
      testing. Women who are suspected of or documented as carrying a breast cancer
      susceptibility gene face a substantially increased lifetime risk of breast (and
      ovarian) cancer ranging from 60-80 % for breast and up to 40 % for ovarian
      cancer. In addition, the disease develops at a young age (the personal risk
      starts increasing at age 25; average age of diagnosis is 40). BRCA-associated
      breast cancers tend to exhibit histologic and histochemical evidence of
      aggressive biologic behavior (usually grade 3, receptor negative) with very fast
      growth rates. In particular BRCA1-associated breast cancer may be
      indistinguishable from fibroadenomas: they appear as well-defined, roundish,
      hypoechoic masses with smooth borders, without posterior acoustic shadowing on
      ultrasound, without associated microcalcifications on mammography, and with
      strong wash-out phenomenon on breast MRI. This article reviews the different
      options that exist for the prevention of familial or hereditary breast cancer and
      the specific difficulties that are associated with the radiological diagnosis of
      these cancers. Lastly, an overview is given of the current evidence regarding the
      effectiveness of the different imaging modalities for early diagnosis of familial
      and hereditary breast cancer.

PMID- 16817123
TI  - [Comparison of different review displays with respect to the detection of low
      contrast details in digital radiographs].
AB  - PURPOSE: Assessment of low-contrast details in digital radiographs on different
      review displays (RD). MATERIALS AND METHODS: 20" flat screen panels (RD1:
      standard color LCD-TFT, RD2: monochrome LCD-TFT for radiological reading, RD1*:
      RD1 with optional image inversion; 205 cd/m (2) luminance, respectively) were
      evaluated. At 30 lx ambient lighting, 10 radiologists gradually increased the
      contrast (constant steps) for both a homogeneous picture and a cutout of a thorax
      radiography of n = 480 simulated nodules until they became recognizable. RESULTS:
      In the case of bright nodules on an anthropomorphic background, the use of image
      inversion produced significantly better results. No other significant differences
      were detected. CONCLUSION: Provided that the working environment is not bright,
      the results suggest that low-cost RD can be used for the recognition of low
      contrast details in radiographies of the chest. Further studies including more
      display models are necessary. Among different ambient lighting and luminance
      settings, these studies should include a closer analysis of the special features
      of digital systems such as brightness/contrast adaptation, picture enlargement
      (zoom shot), and image inversion.

PMID- 16817124
TI  - [Partial k-space sampling with zero filling used with phase-contrast flow
      measurements: in vivo and in vitro validation].
AB  - PURPOSE: To validate the technique of partial k-space sampling and zero filling
      with phase-contrast flow measurements as compared to measurements with full k
      space sampling. MATERIALS AND METHODS: In vitro: A laminar flow phantom was
      utilized to evaluate the effect of partial k-space sampling on the accuracy,
      precision and signal-to-noise ratio of phase-contrast flow measurements. In vivo:
      The effect of partial k-space sampling on the quantification of cardiac output (n
      = 40 patients) and the duration of the scan were evaluated in the ascending aorta
      (n = 37) and pulmonary trunk (n = 34) in a prospective study. RESULTS: Partial k
      space sampling resulted in an increase in the SNR by 2 % in vitro. The precision
      was altered by less than 1 %. Flow volumes were systematically overestimated by
      3.5 %. No significant differences were found in the in vivo measurements of
      cardiac output. The scan duration was reduced by 34 % by utilizing partial k
      space sampling. CONCLUSION: Partial k-space sampling can be used to reduce scan
      time without a significant decrease in the accuracy or precision of phase
      contrast flow measurements in large arteries.

PMID- 16817125
TI  - [Large, cystic papillary thyroid carcinoma in a young man].

PMID- 16817126
TI  - [Progressive metastatic calcification of the lung].

PMID- 16817127
TI  - [Imaging techniques for Moschkowitz syndrome].

PMID- 16817140
TI  - [Gene expression analysis by DNA microarray in papillary thyroid cancer].
AB  - In our study we present chosen elements of microarray analysis of gene expression
      profile in papillary thyroid cancer. The study group included 16 papillary
      thyroid cancer tissues and 16 corresponding normal tissues. Samples were analyzed
      on high density oligonucleotide microarrays (GeneChip HG-U133A) which contain
      22.000 genes. 110 genes, which had significant changed expression, were selected
      by MAS 5.0 program. 3 genes were chosen to the deeper analysis:
      dipeptidylpeptidase 4 (DPP4), fibronectin 1 (FN1), tissue inhibitor of
      metalloproteinase 1 (TIMP1). DPP4-RNA were absent in normal tissue while in
      cancer tissue it was detected in large amount. FN1 and TIMP1 expression were
      detected in normal tissue but markedly increased in papillary thyroid cancer.
      Among these 3 genes DPP4 seems to be the best molecular marker for papillary
      thyroid cancer.

PMID- 16817142
TI  - [The cysteine bonding in TSH receptor and it function in autoantibodies
      recognition].
AB  - The majority of epitopes for TSH receptor (TSHR) stimulating autoantibodies are
      clustered around the Nterminal region of the TSH receptor. The characteristic
      feature of this region is the presence of four cysteine residues. It was proposed
      that cysteines in positions 29 and 41 in the receptor are connected by disulfide
      bonds and they are the target for receptor stimulating antibodies. The present
      study was aimed to check this possibility. The synthetic peptides: peptide
      corresponding to the part of TSHR containing the above 29-41 cysteine bond, the
      peptide similar to this peptide but without disulfide bond and the control
      peptide, containing sequence absent in the receptor were used for rabbit
      immunization. The thyroid status of all immunized rabbits was the same. Rabbits
      immunized with peptides related to TSHR generated antisera reactive with TSHR in
      immunoenzymatic assay. To check specificity of this reaction the influence of the
      peptides and the antisera on TSH binding to the receptor in competitive assay
      (TRAK) and their influence on adenylate cyclase activity were studied. It was
      found that neither synthetic peptides nor antiserum from any rabbit influenced
      TSH binding to the receptor in TRAK. In contrast low, but significant adenylate
      cyclase stimulating activity was noticed for antisera from two of six rabbit
      immunized by peptide containing the disulfide bond. We concluded that such a bond
      between cysteine residues 29 and 41 are present in TSHR in the site of
      stimulating antibodies epitope.

PMID- 16817141
TI  - [Clinical course and treatment of patients with differentiated thyroid carcinoma
      diagnosed during the year 1995].
AB  - The aim of the study was to analyze the clinical course and therapy in patients
      with differentiated thyroid carcinoma (DTC) diagnosed in Poland within the year
      1995. The group of 478 patients with thyroid cancer (57.7% of all thyroid cancer
      cases diagnosed this year in Poland) was analyzed. Patients were diagnosed or
      treated in Maria Sklodowska-Curie Memorial Cancer Center and Institute of
      Oncology, Gliwice Branch. Detailed analysis was performed in 352 patients with
      DTC who were treated by surgery. 292 patients (60%) received adjuvant radioiodine
      therapy. Hormonal (L-thyroxine) treatment was administered to all patients. In 37
      patients (8.6%) local recurrence was observed. 10-year overall survival was 96.4%
      and disease-free survival was respectively 68%. The comparison of Polish data to
      analysis in German population published by Holtzer et al. (Cancer, 2000) was also
      performed in this study. We conclude that DTC therapy, currently recommended in
      our country, gives satisfactory results and that clinical outcome and therapeutic
      methods are similar both in Poland and Germany.

PMID- 16817143
TI  - [Evaluation of the effect of GHRH(1-44)NH2 on the secretion of interleukin-2 (IL
      2) and soluble IL-2 receptor alpha (sIL-2Ralpha) from human peripheral blood
      mononuclear cells in vitro].
AB  - OBJECTIVE: The bidirectional communication between the neuroendocrine and the
      immune systems is now a subject of an intensive investigation. Somatoliberin
      (GHRH) is a hypothalamic hormone that enhances the synthesis and the release of
      growth hormone (GH) from the anterior pituitary cells. Few recent reports
      demonstrate also role of the neuropeptide in the regulation of the immune system
      function. AIM: The aim of the study was to examine the influence of GHRH on IL -2
      as well as sIL -2Ralpha secretion from mitogen-stimulated peripheral blood
      mononuclear cells. MATERIAL AND METHOD: Mononuclear cells (PBMC) were isolated
      from the peripheral blood of healthy adults according to the technique described
      by Boyum. Cells, cultured 24 hours at 37 degrees C in humidified atmosphere of
      95% air and 5% CO2, were stimulated with phytohemaglutinin (PHA; 10 microg/ml),
      and then GHRH(1-44)NH2 at the final concentrations 10(-12), 10(-10), 10(-8) and
      10(-6) M was added to appropriate wells. ELISA kits were used to measure IL-2 and
      sIL-2Ralpha concentrations in the supernatants of cultured cells. Comparisons
      between tested groups were made by U Mann-Whitney test. The differences were
      considered significant if p < 0.05. RESULTS: GHRH stimulated the secretion of IL 
      2 into the supernatants acting significantly at the concentration of 10(-12) M (p
      < 0.001). Moreover, GHRH at concentrations 10(-10) M and 10(-8) M significantly
      increased the secretion of sIL-2Ralpha as well (p < 0.001). Strong positive
      correlation between tested GHRH concentrations and sIL-2Ralpha levels in the
      supernatants was demonstrated (r = 0.8664; p <0.001). CONCLUSIONS: The results
      demonstrate the potential involvement of GHRH in the regulation of T lymphocytes
      secretory function.

PMID- 16817144
TI  - [Macroprolactin in subjects with hyperprolactinaemia: clinical observations and
      relations between free PRL and PRL complexed with IgG].
AB  - In some patients with hyperprolactinaemia a large portion of circulating
      prolactin is bound to authologous gammaglobulin and therefore it is called
      macroprolactin or Big-Big-Prolactin (BB-PRL). THE AIM: of the study was to select
      patients with predominance of macroprolactin and to learn more about the natural
      course of this disorder, in particular about the possible dependence of the
      presence of clinical features from the amount of circulating "free" PRL level,
      and also to search whether the quantitative proportions of both forms of PRL are
      stable or they change parallel to changes of the total serum PRL level. MATERIAL
      AND METHODS: We identified 58 patients with hyperprolactinaemia, in whom BB-PRL
      consisted>or=60% of the total PRL concentration. The predominance of
      macroprolactin was settled using the well accepted method of polyethylene glycol
      (PEG) precipitation of large m.w. serum proteins, followed by contemporary
      immunoradiometric measurement of the total and free PRL levels, and calculation
      of BB-PRL. Repeating such measurements during the long term observation lasting 6
      66 months (mean 33 months), which was possible in 18 our patients (13--with
      idiopathic hyperprolactinaemia and 5--with pituitary adenoma), we could analyze
      the relations between both forms of PRL during the specific treatment, after it's
      cessation and, in few cases--during pregnancy. Apart of that, in 18 patients
      selected from 53 with idiopathic hyperprolactinaemia, we analyzed the shortterm
      alterations in the ratio between free and complexed PRL during the metoclopramide
      PRL stimulation test. RESULTS AND CONCLUSIONS: 1. In hyperprolactinaemic patients
      with predominance of BB-PRL, there was no direct correlation between the presence
      of clinical features and the concentration of residual "free" PRL. 2. During the
      long-term observation, in spite of moderate changes in the total PRL
      concentration induced by the treatment or it's cessation (excluding pregnancy),
      the ratio of "free" PRL and BB-PRL remained stable. 3. During the short time of
      metoclopramide stimulation test, there was a marked rise mainly of the total and
      "free" PRL concentrations, and, in some tested subjects, the predominance of BB
      PRL was lost temporally for 1 to 2 hours.

PMID- 16817145
TI  - Reversal of the sex difference in plasma leptin levels in obese children with
      impaired glucose tolerance.
AB  - INTRODUCTION: Basal leptin level has been demonstrated to correlate positively
      with many indices of obesity, as well as insulin resistance. However, to date,
      little is known about regulation of leptin in obese children with incipient
      glucose metabolic disorders. OBJECTIVE: The aim of this study was to define the
      precise influence of the glucose tolerance status on plasma leptin in obese boys
      and girls separately. MATERIAL AND METHODS: 70 obese children with impaired
      glucose tolerance (IGT) and well-matched 70 normal glucose-tolerant (NGT)
      subjects were examined. Fasting and 2-h post glucose load plasma glucose and
      insulin levels as well as fasting leptin levels were determined, apart from
      anthropometric measurements. RESULTS: Leptin levels were significantly lower in
      girls with IGT compared to NGT girl (17.7+/-6.5 microg/L vs. 23.1+/-7.7 microg/L;
      p<.001). No such difference was observed in boys. In a multiple regression
      analysis adjusting for age and adiposity, in the female group plasma glucose and
      insulin levels 2-h after glucose load were the best predictors of fasting plasma
      leptin (r=-0.49, p<.005 and r=0.34, p<.05; respectively). In boys, plasma insulin
      level 2-h after glucose load was the independent determinant of leptin (r=0.36,
      p<.05). CONCLUSION: The differences between regulation of leptin synthesis in
      girls and boys with simple obesity were found. The stimulatory effect of insulin
      on leptin synthesis was greater in girls with normoglycemia than in girls with
      impaired glucose tolerance.

PMID- 16817146
TI  - [Pituitary resistance to thyroid hormone--a case report].
AB  - Pituitary resistance to thyroid hormone is a very rare cause of hyperthyroidism.
      It is characterized by normal, or elevated TSH concentration with high
      concentration of T3 and T4. Here, we present a case of a 24-year-old woman who
      suffered from mild thyrotoxicosis and diffuse goiter for several years. She had
      elevated fT3 and fT4 with slightly elevated TSH concentration. Pituitary adenoma
      was excluded as magnetic resonance imaging showed normal pituitary gland, alpha
      subunit was within normal range and TSH concentration increased after TRH
      administration. Sonography revealed normoechogenic, slightly enlarged thyroid
      gland. Previously, she was given thiamazole, but without any significant
      amelioration. Thus, the diagnosis of the syndrome of pituitary resistance to
      thyroid hormone was established. The patient was given bromocriptine at a dose of
      10 mg per day. After 2 months of treatment she achieved a state of constant
      euthyrosis and following next few months thyroid volume diminished.

PMID- 16817147
TI  - [Type 1 diabetes as a mask of a neuroendocrine tumour of pancreas].
AB  - Neuroendocrine tumours of pancreas originating from pancreatic islet cells are
      uncommon neoplasms with clinical manifestation depending on a type of hormone
      secreted. Diabetes as a clinical sign of such a tumour has been reported many
      times and is not an uncommon finding but it is generally mild and makes only a
      part ofa whole pattern of symptoms. We report on a case of a malignant
      neuroendocrine pancreatic tumour in 19 years old patient, where diabetes, with a
      clinical course typical for type 1 diabetes, was the first and the main symptom
      of the disease.

PMID- 16817148
TI  - A practical approach to computing power for generalized linear models with
      nominal, count, or ordinal responses.
AB  - Data analysts facing study design questions on a regular basis could derive
      substantial benefit from a straightforward and unified approach to power
      calculations for generalized linear models. Many current proposals for dealing
      with binary, ordinal, or count outcomes are conceptually or computationally
      demanding, limited in terms of accommodating covariates, and/or have not been
      extensively assessed for accuracy assuming moderate sample sizes. Here, we
      present a simple method for estimating conditional power that requires only
      standard software for fitting the desired generalized linear model for a non
      continuous outcome. The model is fit to an appropriate expanded data set using
      easily calculated weights that represent response probabilities given the assumed
      values of the parameters. The variance-covariance matrix resulting from this fit
      is then used in conjunction with an established non-central chi square
      approximation to the distribution of the Wald statistic. Alternatively, the model
      can be re-fit under the null hypothesis to approximate power based on the
      likelihood ratio statistic. We provide guidelines for constructing a
      representative expanded data set to allow close approximation of unconditional
      power based on the assumed joint distribution of the covariates. Relative to
      prior proposals, the approach proves particularly flexible for handling one or
      more continuous covariates without any need for discretizing. We illustrate the
      method for a variety of outcome types and covariate patterns, using simulations
      to demonstrate its accuracy for realistic sample sizes.

PMID- 16817149
TI  - Nested, non-parametric, correlative analysis of microarrays for heterogenous
      phenotype characterization.
AB  - We present a non-parametric approach for qualitatively selecting candidate genes
      to characterize several criteria that are nested among genes selected on the
      basis of their individual, similar effects upon an array-wide closeness measure.
      In this setting, a goal is to obtain a reliable characterization of phenotypes,
      based on very high-dimensional data from a few samples. As opposed to a distance
      based approach, the proposed measure defines closeness based on gene signal
      profiles (functionals) rather than on isolated (numerical) differences in each
      gene between samples. By using such a measure to characterize intensity
      differences, we effectively separate biological from artifactual variation in
      expression, due to tissue effects or signal calibration. Based on this measure,
      we successively examine the significance of the following: a set of similarly
      behaved genes relative to all arrayed genes, a set of candidate genes relative to
      similarly behaved genes, individual candidate genes relative to non-candidates,
      and the direction, as over- or under-expressed, of candidate genes. In each
      setting, sample pairs are the units of analysis, with U-statistics the
      theoretical framework. We illustrate the method on a microarray experiment, where
      the goal is to select sets of genes that characterize a type of skin cancer and
      its histological subtypes.

PMID- 16817154
TI  - Recognition of culture state using two-dimensional gel electrophoresis with an
      artificial neural network.
AB  - Proteomic technologies were applied to the examination of nutrient components in
      culture broth. In bioprocesses, many types of media have been proposed and used
      on the commercial scale. Natural nutrients, the chemical components of which
      cannot be identified completely, are often used in fermentation processes such as
      in the production of baker's yeast, alcoholic beverages, amino acids, and
      pharmaceuticals. The catabolic activities of the microorganisms in these
      processes vary with the species used. We used an artificial neural network (ANN)
      to recognize the sufficiency of chemical elements based on the protein spots
      resolved in 2-DE, and we evaluated this technique using the leave-one-out method.
      We also attempted to reduce the number of input data for spot selection based on
      sensitivity analysis of the ANN, and the selected data were used to improve
      accuracy.

PMID- 16817155
TI  - Calreticulin induces delayed cardioprotection through mitogen-activated protein
      kinases.
AB  - Hypoxic preconditioning (HPC) attenuates tissue injury caused by
      ischemia/reperfusion. The protective mechanisms of HPC involve up-regulation of
      the protective proteins and mitigation of cellular calcium overload. Calreticulin
      (CRT), a Ca(2+)-binding chaperone, plays an important role in regulating calcium
      homeostasis and folding of proteins. The role of CRT in cardioprotection of HPC
      and the pathways determining CRT expression during HPC are not clear. In this
      work, 2-DE and MALDI-MS were employed to analyze CRT differential expression in
      cardiomyocytes subjected to transient hypoxia. Western blotting analysis was used
      to detect the CRT expression and activities of p38 mitogen-activated protein
      kinase (p38 MAPK) and c-Jun NH(2)-terminal kinase (JNK) in myocardium subjected
      to ischemia with and without HPC and sham operation. The hearts from HPC group
      were more resistant to sustained ischemia and had much stronger phosphorylation
      of p38 MAPK, with a reduced phosphorylation of JNK, than controls. The CRT
      expression was positively correlated with the phosphorylation of p38 MAPK and
      negatively correlated with the level of JNK phosphorylation. Furthermore,
      inhibition of the p38 MAPK with SB202190 abolished, while inhibition of the JNK
      with SP600125 enhanced the CRT up-regulation in cardiomyocytes induced by HPC.
      The results indicate that HPC up-regulates CRT expression through the MAPK
      signaling pathways.

PMID- 16817157
TI  - Knowledge-based proteome profiling: considering identified proteins to evaluate
      separation efficiency by 2-D PAGE.
AB  - Proteome profiling techniques rely on the separation of proteins or peptides and
      their subsequent quantification. The reliability of this technique is still
      limited because a proteome profiling result does not necessarily represent the
      true protein composition of the analysed sample, thus seriously hampering proper
      data interpretation. Many experimentally observed proteome alterations are
      biologically not significant. It was the aim of this study to use the knowledge
      of the biological context of proteins in order to establish optimised proteome
      profiling protocols. While 2-D spot patterns of total cell protein fractions were
      found to poorly represent the true protein composition, purified subcellular
      protein fractions were found to better represent the protein composition of the
      analysed sample. The application of a standardised protocol to different kinds of
      cells revealed several striking observations. Firstly, the protein composition of
      cultured cells of various origins is very similar. Secondly, proteome alterations
      observed with the described protocols do make sense from a biologic point of view
      and may thus be considered as truly representative for the analysed samples.
      Thirdly, primary white blood cells isolated from different donors were found to
      show minor, but reproducible and significant individual differences. We designate
      the consideration of known properties of identified proteins in proteome profiles
      as a knowledge-based approach. The present data suggest that this approach may
      tremendously help to improve the applied techniques and assess the results. We
      demonstrate that the fulfilment of well-defined criteria of proteome profiles
      eventually results in reliable and biologically relevant data.

PMID- 16817158
TI  - Glycosylation patterns of human chorionic gonadotropin revealed by liquid
      chromatography-mass spectrometry and bioinformatics.
AB  - Due to their extensive structural heterogeneity, the elucidation of glycosylation
      patterns in glycoproteins such as the subunits of human chorionic gonadotropin
      (hCG), hCG-alpha, and hCG-beta, remains one of the most challenging problems in
      the proteomic analysis of post-translational modifications. In consequence,
      glycosylation is usually studied after decomposition of the intact proteins to
      the proteolytic peptide level. However, by this approach all information about
      the combination of the different glycopeptides in the intact protein is lost. In
      this study we have, therefore, attempted to combine the results of glycan
      identification after tryptic digestion with molecular mass measurements on the
      native starting material of the new first WHO Reference Reagents (RR) for hCG
      alpha (99/720) and hCG-beta (99/650). Despite the extremely high number of
      possible combinations of the glycans identified in the tryptic peptides by HPLC
      MS (>1000 for hCG-alpha and >10 000 for hCG-beta), the mass spectra of intact hCG
      alpha and hCG-beta revealed only a limited number of glycoforms present in hCG
      preparations from pools of pregnancy urines. Peak annotations for hCG-alpha were
      performed with the help of a bioinformatic algorithm that generated a database
      containing all possible modifications of the proteins, including modifications
      possibly introduced during sample preparation such as oxidation or truncation,
      for subsequent searches for combinations fitting the mass difference between the
      polypeptide backbone and the measured molecular masses. Fourteen different
      glycoforms of hCG-alpha, containing biantennary, partly sialylized hybrid-type
      glycans, including methionine-oxidized and N-terminally truncated forms, were
      identified. Mass spectra of high quality were also obtained for hCG-beta,
      however, a database search mass accuracy of +/-5 Da was insufficient to
      unambiguously assign the possible combinations of post-translational
      modifications. In summary, mass spectrometric fingerprints of intact molecules
      were shown to be highly useful for the characterization of glycosylation patterns
      of different hCG preparations such as the new first WHO RR for immunoassays and
      could be the first step in establishing biophysical reference methods for hCG and
      related molecules.

PMID- 16817160
TI  - Capillary electrophoresis-mass spectrometry of citrus endophytic bacteria
      siderophores.
AB  - CE-ESI-MS with a liquid sheath interface and IT mass analyzer was used for
      analysis of siderophores from different strains of Methylobacterium spp. citrus
      endophyte extracts. Three Methylobacterium strains were investigated according to
      positive bioassay tests. Bacteria cultures were grown under Fe(III) absence
      (siderophore producing cultures) and under Fe(III) presence (control cultures).
      Siderophores were extracted from culture supernatant with polystyrene resins. BGE
      and sheath-liquid composition were optimized, respectively, in order to assure
      both, best peak resolution and ESI-MS sensitivity. The best analysis conditions
      were obtained with 100 mmol/L ammonium bicarbonate at pH 8 as BGE and
      methanol:H(2)O 25:75 + 0.05% formic acid as sheath liquid. CZE-ESI-MS analysis
      revealed two possible siderophores, according to bacterium species, presenting
      M(r) of 1004.3 and 798.3 Da.

PMID- 16817161
TI  - Distribution of low-density lipoprotein-bound low-molecular-weight thiols: a new
      analytical approach.
AB  - We have recently demonstrated that low-density lipoprotein (LDL) apoprotein is
      able to bind the most concentrated plasma thiols such as cysteine,
      cysteinylglycine, and homocysteine by disulfide linkage. However, the LIF CE
      assay employed to measure linked thiols was not sensitive enough to verify
      whether low concentrated plasma thiols as glutathione and glutamylcysteine are
      also linked to apoprotein. By modifying sample treatment and electrophoretic
      parameters we set up a new method with an LOQ of about 1.5 nmol/L, by which we
      demonstrate that LDL apoprotein binds all physiological plasma thiols. The
      increased sensitivity was obtained by drying released apoB thiols after reduction
      treatment, dissolving them directly in a low volume of derivatization buffer and
      decreasing the dilution factor of derivatized sample before CE injection.
      Moreover, by increasing the concentration of the electrolyte buffer, we improved
      the selectivity of peaks, in particular between glutathione (GSH) and the
      impurity peak derived from unreacted 5-iodoacetamidofluorescein, which in the
      previous electrophoretic conditions were overlapped. The method optimization,
      reached by searching the best combination between sample matrix and CE run
      buffer, is fully described. Given the potential pathologic significance of
      protein thiolation, the proposed method may be useful to understand the
      mechanisms and the balances that regulate the interaction between thiols and -SH
      free groups of proteins.

PMID- 16817162
TI  - Binding of Ca2+, Mg2+, and heparin by human serum amyloid P component in affinity
      capillary electrophoresis.
AB  - Human serum amyloid P component (SAP) is a glycoprotein circulating in the blood
      and found in association with all types of amyloid (malfolded potein aggregates)
      examined so far. Despite uncertainties regarding the precise function of SAP in
      vivo, the lectin-like properties of this Ca(2+)-activated protein with affinity
      for anionic saccharides and malfolded proteins are well known. The propensity to
      form homomeric penta- or decamers in solution and the selfaggregation in the
      presence of Ca(2+) as well as the tendency of SAP to attach to uncoated fused
      silica have precluded the analysis of SAP by microelectrophoretic methods. We now
      work out conditions to characterize the binding of Ca(2+) and Mg(2+) and the
      binding of heparin to SAP in the presence of divalent metal ions by ACE. The
      results show a strong binding of heparin (sub-muM apparent dissociation
      constants) even in the abscence of Ca(2+) at low ionic strength, pH 8.2. Also, a
      selective interaction with Ca(2+) compared with Mg(2+) is demonstrated. The
      approach will further the use of microelectrophoretic methods to examine the
      interactions of SAP with ligands of putative pathophysiological relevance such as
      lipopolysaccharides and misfolded proteins.

PMID- 16817163
TI  - Capillary electrophoresis-mass spectrometry, an attractive tool for drug
      bioanalysis and biomarker discovery.
AB  - The coupling of CE with MS detection, a relatively recent hyphenated technique,
      has gained increasing respect in the field of bioanalytical applications over the
      past few years. The first part of this review presents CE-MS applications dealing
      with drug bioanalysis, including forensic analysis and metabolism studies.
      Practical considerations to achieve a robust and sensitive CE-MS coupling are
      also presented. It is indeed essential to strictly control some critical
      electrospray parameters, such as the sheath liquid composition and flow rate, the
      nebulizing gas pressure as well as the capillary outlet position. The second part
      of the review critically describes the applications of CE coupled on-line to MS
      for the identification of biomarkers in body fluids for diagnostic purposes.
      Since the sample preparation procedures strongly differ according to the intended
      use (drug bioanalysis or biomarker discovery), they are discussed separately,
      taking into account the particular properties of plasma and urine matrices.

PMID- 16817164
TI  - Glycoform characterization of erythropoietin combining glycan and intact protein
      analysis by capillary electrophoresis - electrospray - time-of-flight mass
      spectrometry.
AB  - Glycosylation of recombinant human erythropoietin (rHuEPO) is a post
      translational process that alters biological activity, solubility and lifetime of
      the glycoprotein in blood, and strongly depends on the type of cell and the cell
      culture conditions. A fast and simple method providing extensive carbohydrate
      information about the glycans present in rHuEPO and other glycoproteins is needed
      in order to improve current methods in drug development or product quality
      control. Here, an improved method for intact rHuEPO glycoform characterization by
      CZE-ESI-TOF MS has been developed using a novel capillary coating and compared to
      a previous study. Both methods allow a fast separation in combination with
      accurate mass characterization of the single protein isoforms. The novel dynamic
      coating provides a separation at an EOF close to zero, enabling better
      separation. This results in an improved mass spectrometric resolution and the
      detection of minor isoforms. In order to assign an unequivocal carbohydrate
      composition to every intact glycoform, a CZE-ESI-MS separation method for
      enzymatically released underivatized N-glycans has been developed. The TOF MS
      allows the correct identification of the glycans due to its high mass accuracy
      and resolution. Therefore, glycan modifications such as acetylation, oxidation,
      sulfation and even the exchange of OH by NH(2) are successfully characterized.
      Information of the protein-backbone molecular mass has been combined with results
      from peptide analysis (revealing information about O-glycosylation) and from the
      glycan analysis, including the detection of as yet undescribed glycans containing
      four antennae and five sialic acids. This allows an unequivocal assignment of an
      overall glycosylation composition to the molecular masses obtained for the intact
      rHuEPO glycoforms.

PMID- 16817165
TI  - Bioanalysis in structured microfluidic systems.
AB  - Microfluidic and lab-on-a-chip devices have attracted widespread interest in
      separation sciences and bioanalysis. Recent designs in microfluidic devices
      extend common separation concepts by exploiting new phenomena for molecular
      dynamics on a length scale of 10 mum and below, giving rise to novel manipulation
      tools and nonintuitive phenomena for microseparations. Here, we focus on three
      very recent developments for bioseparations based on tailored microfluidic
      systems: Single cell navigation, trapping and steering with subsequent on-chip
      lysis, protein separation and LIF detection (Section 3.1), then we report
      dielectrophoretic trapping and separation of large DNA fragments in structured
      microfluidic devices (Section 3.2). Finally, a paradoxial migration phenomenon
      based on thermal fluctuations, periodically arranged microchannels and a biased
      alternating current electric field is presented in Section 3.3.

PMID- 16817166
TI  - Detection and analysis of protein-protein interactions in organellar and
      prokaryotic proteomes by native gel electrophoresis: (Membrane) protein complexes
      and supercomplexes.
AB  - It is an essential and challenging task to unravel protein-protein interactions
      in their actual in vivo context. Native gel systems provide a separation platform
      allowing the analysis of protein complexes on a rather proteome-wide scale in a
      single experiment. This review focus on blue-native (BN)-PAGE as the most
      versatile and successful gel-based approach to separate soluble and membrane
      protein complexes of intricate protein mixtures derived from all biological
      sources. BN-PAGE is a charge-shift method with a running pH of 7.5 relying on the
      gentle binding of anionic CBB dye to all membrane and many soluble protein
      complexes, leading to separation of protein species essentially according to
      their size and superior resolution than other fractionation techniques can offer.
      The closely related colorless-native (CN)-PAGE, whose applicability is restricted
      to protein species with intrinsic negative net charge, proved to provide an
      especially mild separation capable of preserving weak protein-protein
      interactions better than BN-PAGE. The essential conditions determining the
      success of detecting protein-protein interactions are the sample preparations,
      e.g. the efficiency/mildness of the detergent solubilization of membrane protein
      complexes. A broad overview about the achievements of BN- and CN-PAGE studies to
      elucidate protein-protein interactions in organelles and prokaryotes is
      presented, e.g. the mitochondrial protein import machinery and oxidative
      phosphorylation supercomplexes. In many cases, solubilization with digitonin was
      demonstrated to facilitate an efficient and particularly gentle extraction of
      membrane protein complexes prone to dissociation by treatment with other
      detergents. In general, analyses of protein interactomes should be carried out by
      both BN- and CN-PAGE.

PMID- 16817167
TI  - An integrated map of the murine hippocampal proteome based upon five mouse
      strains.
AB  - With the advent of proteomics technologies it is possible to simultaneously
      demonstrate the expression of hundreds of proteins. The information offered by
      proteomics provides context-based understanding of cellular protein networks and
      has been proven to be a valuable approach in neuroscience studies. The mouse
      hippocampus has been a major target of analysis in the search for molecular
      correlates to neuronal information storage. Although human and rat hippocampal
      samples have been successfully subjected to proteomic profiling, no elaborate
      analysis providing the fundamental experimental basis for protein-expression
      studies in the mouse hippocampus has been carried out as yet. This led us to
      construct a master map generated from the individual hippocampal proteomes of
      five different mouse strains. A proteomic approach, based upon 2-DE coupled to MS
      (MALDI-TOF/TOF) has been chosen in an attempt to establish a comprehensive
      reference database of proteins expressed in the mouse hippocampus. 469 individual
      proteins, represented by 1156 spots displaying various functional states of the
      respective gene products were identified. Proteomic profiling of the hippocampus,
      a brain region with a pivotal role for neuronal information processing and
      storage may provide insight into the characteristics of proteins serving this
      highly sophisticated function.

PMID- 16817170
TI  - New designer drug N-(1-phenylcyclohexyl)-3-ethoxypropanamine (PCEPA): studies on
      its metabolism and toxicological detection in rat urine using gas
      chromatographic/mass spectrometric techniques.
AB  - Studies are described on the metabolism and toxicological detection of the
      phencyclidine-derived designer drug N-(1-phenylcyclohexyl)-3-ethoxypropanamine
      (PCEPA) in rat urine using gas chromatographic/mass spectrometric techniques. The
      identified metabolites indicated that PCEPA was metabolized by N-dealkylation, O
      deethylation partially followed by oxidation of the resulting alcohol to the
      corresponding carboxylic acid, hydroxylation of the cyclohexyl ring at different
      positions of PCEPA, N-dealkyl PCEPA, O-deethyl PCEPA, and of the corresponding
      carboxylic acids. Finally, aromatic hydroxylation of PCEPA, the corresponding
      carboxylic acids, and O-deethyl PCEPA, the latter partially followed by oxidation
      to the corresponding carboxylic acid and hydroxylation of the cyclohexyl ring
      could be observed. All metabolites were partially excreted in the conjugated
      form. The authors' systematic toxicological analysis (STA) procedure using full
      scan GC/MS after acid hydrolysis, liquid-liquid extraction, and microwave
      assisted acetylation allowed the detection in rat urine of an intake of a common
      drug users' dose of PCEPA. Assuming a similar metabolism in humans, the STA in
      human urine should be suitable as proof of intake of PCEPA.

PMID- 16817171
TI  - Who needs the concept of 'spirituality'?

PMID- 16817172
TI  - Three-dimensional ultrasound assessment of the cervix for predicting time to
      spontaneous onset of labor and time to delivery in prolonged pregnancy.
AB  - OBJECTIVES: To determine whether three-dimensional (3D) ultrasound including
      power Doppler examination of the cervix is useful for predicting time to
      spontaneous onset of labor or time to delivery in prolonged pregnancy. METHODS: A
      prospective study was conducted in 60 women who went into spontaneous labor. All
      underwent transvaginal 3D power Doppler ultrasound examination of the cervix
      immediately before a prolonged-pregnancy check-up at > or = 41 + 5 gestational
      weeks. Univariate and multivariate logistic regression analysis was used to
      determine which of the following variables predicted spontaneous onset of labor >
      24 h and > 48 h and vaginal delivery > 48 h and > 60 h: length, anteroposterior
      (AP) diameter and width of the cervix and of any cervical funneling; cervical
      volume (cm3); vascularization index (VI); flow index (FI); vascularization flow
      index (VFI); parity; and Bishop score. Multivariate logistic regression analysis
      was carried out both with and without Bishop score as a predictive variable.
      Receiver-operating characteristics (ROC) curves were used to describe the
      diagnostic performance of the tests. RESULTS: The areas under the ROC curves for
      Bishop score, cervical length, and logistic regression models did not differ
      significantly (areas ranging from 0.72 to 0.82). If Bishop score was not included
      in the logistic regression model, cervical length, VI and FI independently
      predicted delivery > 48 h, the likelihood increasing with increasing cervical
      length, decreasing VI and increasing FI. CONCLUSIONS: In prolonged pregnancy
      cervical vascularization as estimated by 3D power Doppler ultrasound is related
      to time to delivery > 48 h, but the likelihood of delivery > 48 h can be
      predicted equally well using Bishop score alone or sonographic cervical length
      alone.

PMID- 16817173
TI  - Bishop score and ultrasound assessment of the cervix for prediction of time to
      onset of labor and time to delivery in prolonged pregnancy.
AB  - OBJECTIVES: To determine the ability of Bishop score and sonographic cervical
      length to predict time to spontaneous onset of labor and time to delivery in
      prolonged pregnancy. METHODS: Ninety-seven women underwent transvaginal
      ultrasound examination and palpation of the cervix at 291-296 days' gestation
      according to ultrasound fetometry at 12-20 weeks' gestation. Sonographic cervical
      length and Bishop score were recorded. Multivariate logistic regression analysis
      was used to determine which variables were independent predictors of the onset of
      labor/delivery < or = 24 h, < or = 48 h, and < or = 96 h. Receiver-operating
      characteristics (ROC) curves were drawn to assess diagnostic performance.
      RESULTS: In nulliparous women (n = 45), both Bishop score and sonographic
      cervical length predicted the onset of labor/delivery < or = 24 h and < or = 48 h
      (area under ROC curve for the onset of labor < or = 24 h 0.79 vs. 0.80, P = 0.94;
      for delivery < or = 24 h 0.81 vs. 0.85, P = 0.64; for the onset of labor < or =
      48 h 0.73 vs. 0.74, P = 0.90; for delivery < or = 48 h 0.77 vs. 0.71, P = 0.50).
      Only Bishop score discriminated between nulliparous women who went into
      labor/delivered < or = 96 h or > 96 h. A logistic regression model including
      Bishop score and cervical length was superior to Bishop score alone in predicting
      delivery < or = 24 h (area under ROC curve 0.93 vs. 0.81, P = 0.03) and superior
      to Bishop score alone and cervical length alone in predicting the onset of labor
      < or = 24 h (area under ROC curve 0.90 vs. 0.79, P = 0.06; and 0.90 vs. 0.80, P =
      0.06). In parous women (n = 52), Bishop score and sonographic cervical length
      predicted the onset of labor/delivery < or = 24 h (area under ROC curve for the
      onset of labor 0.75 vs. 0.69, P = 0.49; for delivery 0.74 vs. 0.70, P = 0.62),
      but only Bishop score discriminated between women who went into labor/delivered <
      or = 48 h and > 48 h. Three parous women had not gone into labor and six had not
      given birth at 96 h. In parous women logistic regression models including both
      Bishop score and cervical length did not substantially improve prediction of the
      time to onset of labor/delivery. CONCLUSIONS: In prolonged pregnancy Bishop score
      and sonographic cervical length have a similar ability to predict the time to the
      onset of labor and delivery. In nulliparous women the use of logistic regression
      models including Bishop score and cervical length is likely to offer better
      prediction of the onset of labor/delivery < or = 24 h than the use of the Bishop
      score alone.

PMID- 16817174
TI  - Prevalence of social phobia and its comorbidity with psychiatric disorders in
      Iran.
AB  - This study explored the prevalence of social phobia (SP) in the general
      population of Iran, the sociodemographic characteristics of subjects with SP, and
      its comorbidity with the other lifetime psychiatric disorders. Our study was part
      of the nationwide study on the prevalence of psychiatric disorders in Iran.
      Overall, 25,180 Iranian subjects, age 18 years and over, from urban and rural
      areas of Iran were selected by a clustered random sampling method and interviewed
      face-to-face by 250 trained clinical psychologists using DSM-IV diagnostic
      criteria. Out of 12,398,235 households, 7,795 households in the form of 1,559
      clusters of five households were selected. The statistical framework was based on
      the household lists available from the Department of Health in the provinces. The
      response rate was 90%. The lifetime prevalence of SP was 0.82%. The rate was 0.4%
      in males and 1.3% in females. The rate was higher in younger age groups and
      widows/widowers. It was not related to educational level and residential area.
      Specific phobia (66.7%), obsessive-compulsive disorder (17.4%), major depressive
      disorder (15%), and panic disorder (12.1%) were the most common lifetime
      psychiatric disorders among subjects with SP. The rate of SP in Iran is more
      similar to that in other Asian countries, and it is lower than that in Western
      countries. The rate of other psychiatric disorders among subjects with SP is more
      than that in the general population, and the most common psychiatric disorders
      were the other anxiety disorders and major depressive disorder.

PMID- 16817175
TI  - First report of prevalence of non-syndromic hereditary prosopagnosia (HPA).
AB  - Acquired prosopagnosia (PA) is a rare condition after, for example, a stroke or
      brain injury. The congenital form of PA is generally considered to be even less
      common. Beside a few single case reports and anecdotal mentioning of familial
      cases no data on the epidemiology exists. Following a questionnaire-based
      screening in local secondary schools and at our medical faculty, candidates
      suspicious for PA underwent a semi-structured interview followed by examinations
      of first degree relatives. Among 689 local pupils and medical students of our
      university we found 17 with congenital PA. This corresponds to a prevalence rate
      of 2.47% (95% CI 1.31-3.63). The frequency is among the highest known for a
      monogenic disorder. All those index subjects (n = 14) of the target group who
      agreed to further examinations of their family members had other first degree
      relatives with the same cognitive disorder. This study provides epidemiological
      evidence that congenital PA is a very common cognitive disorder which almost
      always runs in families. The segregation pattern of this hereditary prosopagnosia
      (HPA) is fully compatible with autosomal dominant inheritance.

PMID- 16817176
TI  - Feasibility and short-term efficacy of percutaneous mitral annular reduction for
      the therapy of functional mitral regurgitation in patients with heart failure.
AB  - BACKGROUND: While functional mitral regurgitation (MR) commonly accompanies heart
      failure and contributes to heart failure progression, mitral repair in the
      setting of HF is not routinely practiced because of the attendant significant
      morbidity and mortality. This limitation has fostered the development of
      percutaneous devices to reduce MR, and our group has recently reported the short-
      and long-term effectiveness of a percutaneous mitral annuloplasty device placed
      in the coronary sinus (Percutaneous Mitral Annuloplasty Device (PMAD), Cardiac
      Dimensions(R), Inc., Kirkland, WA) in reducing MR in experimental animal models
      of heart failure with associated MR. In this article, we report results of a
      "first-in-human" study of temporary placement of the PMAD device. The aim of this
      study was to demonstrate the feasibility and safety of temporary deployment of
      this device in patients with functional MR in association with heart failure.
      METHODS: Five patients undergoing scheduled coronary angiography with heart
      failure and functional MR (mean age 52 +/- 9 [SD] years) were recruited, and four
      had anatomy suitable for deployment of the device. Transthoracic echocardiography
      and coronary angiography were performed before and after temporary placement and
      tensioning of the PMAD via the right internal jugular vein. RESULTS: Temporary
      deployment of the device resulted in a significant reduction in the septal
      lateral mitral annular dimension from 35.5 +/- 4.7 to 32.2 +/- 4.6 mm (P = 0.02),
      with evidence of a reduction in the MR color Doppler area from 98.3 +/- 43.6 to
      83.3 +/- 35.1 mm(2) (P = 0.09). There were no complications. CONCLUSIONS: This
      first-in-human study of a novel device for percutaneous treatment of functional
      MR has shown that temporary placement of this device in the coronary sinus/great
      cardiac vein of patients with heart failure and MR is feasible and safe. Evidence
      of temporary reduction in MR and a reduction in mitral annular area indicate
      promise for device effectiveness in chronic implantation.

PMID- 16817177
TI  - Early administration of abciximab bolus in the emergency department improves
      angiographic outcome after primary PCI as assessed by TIMI frame count: results
      of the early ReoPro administration in myocardial infarction (ERAMI) trial.
AB  - OBJECTIVES: We assessed the safety and efficacy of early administration of
      abciximab prior to percutaneous coronary intervention (PCI) in acute myocardial
      infarction (AMI) patients. BACKGROUND: Research suggests that platelet
      glycoprotein IIb/IIIa receptor inhibitors, e.g. abciximab, may improve myocardial
      perfusion. In particular, early administration in the emergency department, prior
      to PCI, may result in more effective reperfusion. METHODS: Eighty AMI patients
      with planned PCI were randomized in a double-blind fashion to receive a 0.25
      mg/kg abciximab bolus either "early" in the emergency department or "late" in the
      catheterization laboratory after angiographic assessment. In total, 74 patients
      underwent PCI after diagnostic angiography, all of which then received an
      abciximab infusion of 0.125 microg/kg/min for 12 hr. RESULTS: Prior to PCI, no
      significant differences were observed between the two groups regarding the
      angiographic endpoints or ST-segment resolution. After PCI, thrombolysis in MI
      (TIMI) frame count (TFC) was significantly improved in patients treated early
      rather than in those treated late (23 +/- 10 vs. 41 +/- 35; P = 0.02). Consistent
      trends, also favoring early treatment, were observed for TIMI flow grade 3 (TFG
      3), corrected TFC (CTFC), and TIMI myocardial perfusion grade 3 (TMPG 3). Nine
      deaths (4 early, 5 late) and six significant bleeds (4 early, 2 late) were
      observed at 30 days after randomization. CONCLUSIONS: Early administration of
      abciximab is both feasible and safe in patients planned for primary PCI,
      increasing coronary flow and myocardial reperfusion after PCI, as demonstrated by
      significantly decreased TFC scores and trends toward improvements in TFG, CTFC,
      and TMPG.

PMID- 16817178
TI  - Drug-eluting stent supported percutaneous coronary intervention for unprotected
      left main disease.
AB  - OBJECTIVES: This study sought to determine the clinical and angiographic outcomes
      of unselected patients receiving drug-eluting stents for unprotected left main
      disease. BACKGROUND: The results of several series of percutaneous coronary
      intervention (PCI) for left main disease in the pre-drug-eluting stent era have
      arisen concerns on the safety and mid-term efficacy of PCI. METHODS: Consecutive
      patients with unprotected left main disease were considered eligible for drug
      eluting stent supported PCI. The surgical risk score (risk of death within 1
      month) of each patient was calculated according to the European System for
      Cardiac Operative Risk Evaluation (EuroSCORE) model. RESULTS: One-hundred and one
      patients with unprotected left main disease underwent PCI. The mean EuroSCORE was
      19 +/- 23. Successfully left main stenting was performed in 98 patients (primary
      success rate 97%). The overall 1-month mortality rate was 9.9%. The 1-month
      mortality rate was 50% in patients with acute myocardial infarction (AMI) on
      presentation, and 4.5% in patients without AMI on presentation. The 1-month
      mortality rate of patients with a risk score <13 was 3%, while it was 21% in
      patients with a risk score >or=13. At 6 months, the mortality rate of the entire
      cohort of patients increased to 12.8%, and the one of the non-AMI patients to
      7.8%. Survival rate was 86% +/- 4% (mean follow-up 295 +/- 175 days). Target
      vessel revascularization was performed in 14 patients (16%). The 6-month in
      segment restenosis rate was 16%. CONCLUSION: Drug-eluting stent supported PCI may
      provide early and mid-term outcomes comparable or superior to those expected from
      coronary artery surgery. (c) 2006 Wiley-Liss, Inc.

PMID- 16817180
TI  - American psychology and the religious imagination.
AB  - In just three generations, American psychology grew from a fledgling science to a
      culturally authoritative discipline. Standard accounts of psychology's meteoric
      rise typically omit what most needs to be illuminated: the resonance between
      psychological theory and the symbolic universe underlying America's popular
      religious imagination. This article sketches a cultural history of American
      psychology by examining how many of its core concepts invoke a metaphysical
      horizon associated with the nation's heritage of unchurched spirituality.

PMID- 16817179
TI  - The social control of behavior control: behavior modification, Individual Rights,
      and research ethics in America, 1971-1979.
AB  - In 1971, the U.S. Senate Subcommittee on Constitutional Rights began a three-year
      study to investigate the federal funding of all research involving behavior
      modification. During this period, operant programs of behavior change,
      particularly those implemented in closed institutions, were subjected to specific
      scrutiny. In this article, I outline a number of scientific and social factors
      that led to this investigation and discuss the study itself. I show how
      behavioral scientists, both individually and through their professional
      organizations, responded to this public scrutiny by (1) self-consciously altering
      their terminology and techniques; (2) considering the need to more effectively
      police their professional turf; and (3) confronting issues of ethics and values
      in their work. Finally, I link this episode to the formation of the National
      Commission for the Protection of Human Subjects of Biomedical and Behavioral
      Research, whose recommendations resulted in changes to the ethical regulation of
      federally funded human subjects research that persist to the present day.

PMID- 16817181
TI  - The rise of Soviet sociolinguistics from the ashes of Volkerpsychologie.
AB  - Nineteenth-century Russian philology was dominated by an approach derived from
      German Volkerpsychologie. Language and social consciousness were viewed as
      embodiments of "national-popular psychology." The shortcomings of this approach
      were becoming apparent at the end of the prerevolutionary period, but it was only
      in the 1920s that the hegemony of Volkerpsychologie was decisively challenged.
      Volkerpsychologie was attacked in the name of "objective psychology," and
      concrete studies of the relationship between language and social structure were
      carried out. By the end of the 1920s, volkerpsychologische ideas were subsumed
      into a new and progressive form of sociological linguistics.

PMID- 16817184
TI  - Relationship between abdominal and pelvic floor muscle activation and
      intravaginal pressure during pelvic floor muscle contractions in healthy
      continent women.
AB  - AIM: Activation of the abdominal muscles might contribute to the generation of a
      strong pelvic floor muscle contraction, and consequently may contribute to the
      continence mechanism in women. The purpose of this study was to determine the
      abdominal muscle activation levels and the patterns of muscle activity associated
      with voluntary pelvic floor muscle (PFM) contractions in urinary continent women.
      METHODS: Fifteen healthy continent women participated. They performed three
      maximal contractions of each of the four abdominal muscles and of their PFMs
      while in supine. Abdominal and PFM activity was recorded using electromyography
      (EMG), and intravaginal pressure was recorded using a custom modified Femiscan
      probe. RESULTS: During voluntary maximal PFM contractions, rectus abdominus was
      activated to 9.61 (+/-7.42)% maximal voluntary electrical activity (MVE),
      transversus abdominus was activated to 224.30(+/-47.4)% MVE, the external
      obliques were activated to 18.72(+/-13.33)% MVE, and the internal obliques were
      activated to 81.47(+/-63.57)% MVE. A clear pattern of activation emerged, whereby
      the transversus abdominus, internal oblique, and rectus abdominus muscles worked
      with the PFM in the initial generation of maximal intravaginal pressure. PFM
      activity predominated in the initial rise in lower vaginal pressure, with later
      increases in pressure (up to 70% maximum pressure) being associated with the
      combined activation of the PFM, rectus abdominus, internal obliques, and
      transverses abdominus. These abdominal muscles were the primary source of
      intravaginal pressure increases in the latter 30% of the task, whereas there was
      little increase in PFM activation from this point on. The external oblique
      muscles showed no clear pattern of activity, but worked at approximately 20% MVE
      throughout the PFM contractions, suggesting that their role may be predominantly
      in postural setting prior to the initiation of intravaginal pressure increases.
      CONCLUSIONS: Defined patterns of abdominal muscle activity were found in response
      to voluntary PFM contractions in healthy continent women.

PMID- 16817185
TI  - Early outcomes of mid-urethral slings for female stress urinary incontinence
      stratified by valsalva leak point pressure.
AB  - AIMS: To assess the early results of mid-urethral slings placed via the
      transobturator approach (TVT-O) for stress urinary incontinence (SUI) in women
      with high (>60 cm H(2)O) and low (<or=60 cm H(2)O) valsalva leak point pressure
      (VLPP). MATERIALS AND METHODS: Forty-three women with urodynamically proven SUI
      underwent TVT-O. Patients were divided into either high (>60 cm H(2)O) or low
      (<or=60 cm H(2)O) VLPP categories based on preoperative urodynamic studies.
      Patient outcomes were assessed based on degree of postoperative SUI as either dry
      (no pads, no SUI), or wet (any leakage). Follow-up visits were at 1, 6, 12, and
      24 weeks. RESULTS: Overall, 65% (28/43) women were cured following TVT-O for SUI.
      When stratified based on preoperative VLPP, 77% (24/31) of patients with VLPP
      greater than 60 were cured while only 25% (3/12) of patients with VLPP less than
      or equal to 60 were cured. No intraoperative complications were noted. The odds
      of continued SUI following TVT-O were 12 times greater for women with VLPP <or=60
      compared to those with VLPP >60. CONCLUSIONS: With limited follow up, TVT-O
      appears to be a safe and effective surgical treatment for female SUI producing
      excellent results in patients with VLPP >60 cm/H(2)0. Patients with low VLPP may
      consider conventional, retropubic mid-urethral slings or other procedures as
      treatment for SUI.

PMID- 16817187
TI  - Characterization of EGF coupling to aminated silicone rubber surfaces.
AB  - Tethering of growth factors to biomaterial substrates via a polyethylene glycol
      (PEG) spacer has been established as a means of controlling dosage and
      conformation of the protein at the material surface, while retaining biological
      activity. However, the extent of modification through a comparison of bound
      versus unbound protein has not generally been characterized. In this work,
      covalent tethering of epidermal growth factor (EGF) to allylamine plasma modified
      polydimethylsiloxane (PDMS) substrates is characterized to determine the nature
      of the bound growth factor and to optimize the conditions for the reaction.
      Tethering is achieved via conjugation of EGF with homobifunctional N
      hydroxysuccinimide (NHS) ester of PEG-butanoic acid (SBA2-PEG) in solution,
      followed by exposure of the pegylated EGF to the aminated surfaces (solution
      first reaction). SDS-PAGE analysis indicates that a low ratio of EGF:PEG is
      required to maximize the yield of the EGF-PEG reaction; a relatively short
      reaction time is needed to limit hydrolysis of the NHS ester. With increasing
      amounts of PEG and a higher reaction time, a higher fraction of the EGF can be
      covalently tethered to the surfaces, as shown by binding of 125I-labeled EGF and
      subsequent washing with sodium dodecyl sulfate (SDS) to remove adsorbed protein.
      However, even under the optimal reaction conditions established by the SDS-PAGE
      analysis, higher molecular weight EGF-PEG complexes are observed by SDS-PAGE and
      matrix-assisted laser desorption/ionization (MALDI). The presence of these
      complexes, as well as unreacted growth factor, can lead to a surface of
      heterogeneous composition. While these surfaces were found to have biological
      activity, stimulating the adhesion and growth of corneal epithelial cells versus
      PDMS controls, further optimization of reaction conditions, including the use of
      a homobifunctional PEG linker and possibly separation of reaction species are
      required to achieve a uniformly active and well-defined biomaterial surface.

PMID- 16817188
TI  - High-throughput and real-time study of single cell electroporation using
      microfluidics: effects of medium osmolarity.
AB  - Electroporation has been widely accepted as an important tool for the delivery of
      exogenous molecules into cells. Previous mechanistic studies have been carried
      out by observing either the average behavior from a large population of cells or
      the response from a small number of single cells. In this study, we demonstrated
      a novel microfluidic method with high throughput (up to 30 Hz) for real-time
      studies of single cell electroporation events. Electroporation occurred when
      cells flowed through a section of a microfluidic channel defined by special
      geometry. A CCD camera was used to monitor the response of cells starting from
      the onset of the electroporation. We studied the swelling of Chinese hamster
      ovary cells and the rupture of cell membrane during electroporation using this
      technique. We applied buffers with different osmolarities to investigate the
      effects of medium osmolarity, based on results from a population of single cells.
      We were able to establish the distributions of the rates of swelling and membrane
      rupture in the cell population. We also explored establishing the correlation
      between the property (the cell diameter) and the behavior (the swelling rate) of
      single cells. Our results indicated that the processes of swelling and rupture
      occurred more rapidly in the hypotonic or hypertonic buffers than in the isotonic
      buffer. Statistical analysis did not reveal strong linear correlation between the
      cell size and the swelling rate. These proof-of-concept studies reveal the
      potential of applying microfluidics to study electroporation of a cell population
      at single cell level in real time with high throughput. The limitations
      associated with this approach were also addressed.

PMID- 16817189
TI  - Visualising fouling of a chromatographic matrix using confocal scanning laser
      microscopy.
AB  - Confocal scanning laser microscopy (CSLM) was used to visualise the spatial
      location of foulants during the fouling of Q Sepharose FF matrix in finite batch
      experiments and for examining the subsequent effectiveness of clean-in-place
      (CIP) treatments in cleaning the heavily fouled beads. Beads were severely fouled
      with partially clarified E. coli homogenate by contacting the beads with the
      foulant for contact times of 5 min, 1 or 12 h. The use of two different
      fluorescent dyes, PicoGreen and Cy5.5, for labelling genomic PicoGreen-labelled
      dsDNA and protein respectively, allowed the direct observation of the
      chromatographic beads. The extent of fouling was assessed by measuring the
      subsequent adsorption of Cy5.5-labelled BSA to the beads. Control studies
      established that the labelling of BSA did not affect significantly the protein
      properties. In the control case of contacting the unfouled matrix with Cy5.5
      labelled BSA, protein was able to penetrate the entire matrix volume. After
      fouling, Cy5.5-labelled BSA was unable to penetrate the bead but only to bind
      near the bead surface where it slowly displaced PicoGreen-conjugated dsDNA, which
      bound only at the exterior of the beads. Labelled host cell proteins bound
      throughout the bead interior but considerably less at the core; suggesting that
      other species might have occupied that space. The gross levels of fouling
      achieved drastically reduced the binding capacity and maximum Cy5.5-labelled BSA
      uptake rate. The capacity of the resin was reduced by 2.5-fold when incubated
      with foulant for up to 1 h. However, when the resin was fouled for a prolonged
      time of 12 h a further sixfold decrease in capacity was seen. The uptake rate of
      Cy5.5-labelled BSA decreased with increased fouling time of the resin. Incubating
      the fouled beads in 1 M NaCl dissociated PicoGreen-labelled dsDNA from the bead
      exterior within 15 min of incubation but proved ineffective in removing all the
      foulant protein. Cy5.5-labelled BSA was still unable to bind beyond the outer
      region of the beads. A harsher CIP treatment of 1 M NaCl dissolved in 1 M NaOH
      was also ineffective in removing all the foulant protein but did remove PicoGreen
      conjugated dsDNA within 15 min of incubation. Cy5.5-labelled BSA was able to bind
      throughout the bead interior after this more aggressive CIP treatment but at a
      lower capacity than in the case of fresh beads. The competitive adsorption of
      BacLight Red-labelled whole cells or cell debris and PicoGreen-conjugated dsDNA
      was also visualised using CSLM.

PMID- 16817190
TI  - Rat choroid plexuses contain myeloid progenitors capable of differentiation
      toward macrophage or dendritic cell phenotypes.
AB  - The interface between the blood and the cerebrospinal fluid (CSF) is formed by
      the choroid plexuses (CPs), which are specialized structures located within the
      brain ventricles. They are composed of a vascularized stroma surrounded by a
      tight epithelium that controls molecular and cellular traffic between the blood
      and the CSF. Cells expressing myeloid markers are present within the choroidal
      stroma. However, the exact identity, maturation state, and functions of these CP
      associated myeloid cells are not fully clarified. We show here that this cell
      population contains immature myeloid progenitors displaying a high proliferative
      potential. Thus, in neonate rats and, to a lesser extent, in adult rats, cultured
      CP stroma cells form large colonies of macrophages, in response to M-CSF or GM
      CSF, while, under the same conditions, peripheral blood monocytes do not. In
      addition, under GM-CSF treatment, free-floating colonies of CD11c(+) monocytic
      cells are generated which, when restimulated with GM-CSF and IL-4, differentiate
      into OX62(+)/MHC class II(+) dendritic cells. Interestingly, in CP stroma
      cultures, myeloid cells are found in close association with fibroblastic-like
      cells expressing the neural stem-cell marker nestin. Similarly, in the developing
      brain, macrophages and nestin(+) fibroblastic cells accumulate in vivo within the
      choroidal stroma. Taken together, these results suggest that the CP stroma
      represents a niche for myeloid progenitors and may serve as a reservoir for brain
      macrophages.

PMID- 16817191
TI  - Adsorption of bisphosphonate onto hydroxyapatite using a novel co-precipitation
      technique for bone growth enhancement.
AB  - Premature bone resorption and remodeling by osteoclasts can limit the longevity
      of implant fixation and recovery time. Orally administered bisphosphonates (BPs)
      have been used to inhibit osteoclast action at the implant/bone interface.
      Ideally, these should be delivered at the interface with the osteoblast-active
      hydroxyapatite (HA) for maximum effect. This investigation introduces a novel BP
      loading technique to achieve improved BP release from a simulated body fluid
      grown HA (SBF-HA) with the aim of improving implant fixation. A solution co
      precipitation technique incorporates the BP (pamidronate) into a thin SBF-HA
      coating. Surface analysis, using X-ray photoelectron spectroscopy (XPS), of the
      resultant coating was employed to confirm the presence of the adsorbed BP on the
      surface of SBF-HA. XPS analysis was also used to determine the optimal adsorption
      process. Osteoclast cell culture experiments confirmed the biological
      effectiveness of BP adsorption and proved that the pamidronate was biologically
      active, causing both decreased osteoclast numbers and decreased resorption.

PMID- 16817192
TI  - Effects of biomaterial surface chemistry on the adhesion and biofilm formation of
      Staphylococcus epidermidis in vitro.
AB  - The formation of biofilm, a structured community of bacteria enclosed in slime,
      is a significant virulence factor in medical-device-centered infection. The
      development of cardiovascular device infection can be separated into two phases:
      initial bacterial adhesion and aggregation, followed by proliferation and
      production of slime. It is possible to modulate the adhesion and biofilm
      formation of Staphylococcus epidermidis, a commensal skin bacterium commonly
      found on infected medical devices, through biomaterial surface chemistry. This
      study examines bacterial adhesion and biofilm formation on surface-modified
      polyethylene terephthalate (PET), including surfaces with varying hydrophilic,
      hydrophobic, and ionic character. Bacterial adhesion and biofilm formation were
      observed over 48 hours in phosphate-buffered saline (PBS) and 20% pooled human
      serum. The hydrophilic surface (PAAm) had significantly less nonspecific adhesion
      of bacteria than that in the control (PET) and other surfaces, when cultured in
      PBS (P < 0.0001). Charged surfaces, both anionic and cationic, had increased
      adhesion and aggregation of bacteria in comparison with the control (PET) in the
      presence of serum proteins over 24 hours (P < 0.0001). Bacteria cultured in serum
      on the charged surfaces did not have significantly different amounts of biofilm
      formation compared with that of the control (PET) surface after 48 hours. This
      study showed that biomaterial surface chemistry characteristics impact initial
      adhesion and aggregation of S. epidermidis on biomaterials.

PMID- 16817193
TI  - Dystonia, mental deterioration, and dyschromatosis symmetrica hereditaria in a
      family with ADAR1 mutation.
AB  - A family with dystonia associated with dyschromatosis symmetrica hereditaria
      (DSH), mental deterioration, and tissue calcification is described. The proband
      possessed an adenosine deaminase acting on the RNA 1 gene (ADAR1) mutation
      Gly1007Arg. This ADAR1 mutation could disturb RNA editing at Q/R sites of
      glutamate receptor in the brain and increase Ca(2+) influx into neurons, which is
      thought to induce dystonia and mental deterioration. The observations in our
      family raise the possibility that the ADAR1 mutation might be a direct cause or a
      predisposing factor for heredodegenerative dystonia. Further investigation of
      ADAR1 mutations will shed light on the genotype-phenotype correlation in DSH.

PMID- 16817195
TI  - Pseudoathetosis: report of three patients.
AB  - We report on 3 patients with pseudoathetosis, which are involuntary, slow,
      writhing movements due to loss of proprioception.

PMID- 16817194
TI  - Noninvasive cortical stimulation with transcranial direct current stimulation in
      Parkinson's disease.
AB  - Electrical stimulation of deep brain structures, such as globus pallidus and
      subthalamic nucleus, is widely accepted as a therapeutic tool for patients with
      Parkinson's disease (PD). Cortical stimulation either with epidural implanted
      electrodes or repetitive transcranial magnetic stimulation can be associated with
      motor function enhancement in PD. We aimed to study the effects of another
      noninvasive technique of cortical brain stimulation, transcranial direct current
      stimulation (tDCS), on motor function and motor-evoked potential (MEP)
      characteristics of PD patients. We tested tDCS using different electrode montages
      [anodal stimulation of primary motor cortex (M1), cathodal stimulation of M1,
      anodal stimulation of dorsolateral prefrontal cortex (DLPFC), and sham
      stimulation] and evaluated the effects on motor function--as indexed by Unified
      Parkinson's Disease Rating Scale (UPDRS), simple reaction time (sRT) and Purdue
      Pegboard test--and on corticospinal motor excitability (MEP characteristics). All
      experiments were performed in a double-blinded manner. Anodal stimulation of M1
      was associated with a significant improvement of motor function compared to sham
      stimulation in the UPDRS (P < 0.001) and sRT (P = 0.019). This effect was not
      observed for cathodal stimulation of M1 or anodal stimulation of DLPFC.
      Furthermore, whereas anodal stimulation of M1 significantly increased MEP
      amplitude and area, cathodal stimulation of M1 significantly decreased them.
      There was a trend toward a significant correlation between motor function
      improvement after M1 anodal-tDCS and MEP area increase. These results confirm and
      extend the notion that cortical brain stimulation might improve motor function in
      patients with PD.

PMID- 16817196
TI  - Balance in Parkinson's disease under static and dynamic conditions.
AB  - We tested balance performance in 15 on phase Parkinson's disease (PD) patients (8
      nonfallers, PD-NF; 7 fallers, PD-F) during quiet stance (stabilometry) and on a
      platform continuously moving in the anteroposterior direction (dynamic test).
      Neither stabilometry (eyes open or closed) nor the dynamic test (eyes open)
      separated PD-F from PD-NF. With the dynamic test, eyes closed, PD-F with respect
      to PD-NF showed larger head oscillations, smaller cross-correlation between head
      and malleolus motion (more so in patients with low Unified Parkinson's Disease
      Rating Scale, or UPDRS), and larger delays of head with respect to platform
      motion. Further, across all PD patients, head displacement increased with the
      equivalent levodopa dose, indicating a trend for medication to worsen balancing
      capacity while improving UPDRS. The dynamic test is a sensitive tool for
      detecting instability in PD-F since absence of visual flow selectively impairs
      both association between body segment movements and anticipatory adjustments.

PMID- 16817197
TI  - Leucine-rich repeat kinase 2 (LRRK2) mutations in a Swedish Parkinson cohort and
      a healthy nonagenarian.
AB  - Specific variants of Leucine-rich repeat kinase 2 (LRRK2) have been shown to
      associate with Parkinson's disease (PD). Several mutations have been found in PD
      populations from different parts of the world. We investigated the occurrence of
      three mutations (R1441G/C/H, G2019S, and I2020T) in our Swedish case-control
      material and identified four carriers of the G2019S mutation in 284 PD cases and
      1 95-year-old carrier in 305 controls. The other two variants were absent in our
      material. We conclude that the LRRK2 G2019S mutation constitutes a significant
      factor for PD in the Swedish population and that it is not completely penetrant.

PMID- 16817198
TI  - Botulinum toxin A may be efficacious as treatment for jaw tremor in Parkinson's
      disease.
AB  - Jaw tremor in Parkinson's disease (PD) may not respond well to conventional
      treatment. It causes embarrassment and social handicap. We piloted the use of
      botulinum toxin (BTX) injections in three patients with PD jaw tremor. BTX A
      (Dysport; mean, 53 U; range, 30-100 U) was given into each masseter muscle.
      Outcome was assessed by subjective and clinical improvement and by video
      recording before and 4 to 9 weeks after injections. There was an excellent
      response in all without side effects. BTX injections into the masseter may
      effectively improve jaw tremor and be useful in PD and other conditions.

PMID- 16817199
TI  - Iron metabolism in Parkinsonian syndromes.
AB  - Growing evidence suggests an involvement of iron in the pathophysiology of
      neurodegenerative diseases. Several of the diseases are associated with
      parkinsonian syndromes, induced by degeneration of basal ganglia regions that
      contain the highest amount of iron within the brain. The group of
      neurodegenerative disorders associated with parkinsonian syndromes with increased
      brain iron content can be devided into two groups: (1) parkinsonian syndromes
      associated with brain iron accumulation, including Parkinson's disease, diffuse
      Lewy body disease, parkinsonian type of multiple system atrophy, progressive
      supranuclear palsy, corticobasal ganglionic degeneration, and Westphal variant of
      Huntington's disease; and (2) monogenetically caused disturbances of brain iron
      metabolism associated with parkinsonian syndromes, including aceruloplasminemia,
      hereditary ferritinopathies affecting the basal ganglia, and panthotenate kinase
      associated neurodegeneration type 2. Although it is still a matter of debate
      whether iron accumulation is a primary cause or secondary event in the first
      group, there is no doubt that iron-induced oxidative stress contributes to
      neurodegeneration. Parallels concerning pathophysiological as well as clinical
      aspects can be drawn between disorders of both groups. Results from animal models
      and reduction of iron overload combined with at least partial relief of symptoms
      by application of iron chelators in patients of the second group give hope that
      targeting the iron overload might be one possibility to slow down the
      neurodegenerative cascade also in the first group of inevitably progressive
      neurodegenerative disorders.

PMID- 16817200
TI  - Differential effects of imatinib on PDGF-induced proliferation and PDGF receptor
      signaling in human arterial and venous smooth muscle cells.
AB  - Platelet-derived growth factor (PDGF) has been implicated in smooth muscle cell
      (SMC) proliferation, a key event in the development of myointimal hyperplasia in
      vascular grafts. Recent evidence suggests that the PDGF receptor (PDGFR) tyrosine
      kinase inhibitor, imatinib, can prevent arterial proliferative diseases. Because
      hyperplasia is far more common at the venous anastomosis than the arterial
      anastomosis in vascular grafts, we investigated whether imatinib also inhibited
      venous SMC (VSMC) proliferation, and examined possible differences in its
      mechanism of action between VSMC and arterial SMC (ASMC). Human ASMC and VSMC
      were stimulated with PDGF-AB, in the presence or absence of imatinib (0.1-10
      microM). Proliferation was assayed using the 5-bromo-2'-deoxyuridine (BrdU)
      incorporation assay, while PDGFR, Akt and ERK1/2-mitogen activated protein kinase
      (MAPK) signaling pathways were investigated by immunoblotting. The proliferative
      response to PDGF at 50 and 100 ng/ml was 32 and 43% greater, respectively, in
      VSMC than in ASMC. Similarly, PDGF-stimulated proliferation was more sensitive to
      inhibition by imatinib in VSMC than ASMC (IC(50) = 0.05 microM vs. 0.4 microM; P
      < 0.01). Imatinib also more effectively inhibited PDGF-induced phosphorylation of
      PDGFRbeta and Akt in VSMC, compared to ASMC. These data highlight inherent
      pharmacodynamic differences between VSMC and ASMC in receptor and cell signaling
      functions and suggest that imatinib therapy may be useful for the prevention of
      venous stenosis in vascular grafts.

PMID- 16817202
TI  - Different expression of synemin isoforms in glia and neurons during nervous
      system development.
AB  - The synemin gene encodes proteins belonging to the intermediate filament family.
      These proteins confer resistance to mechanical stress and modulate cell shape.
      Three synemin isoforms, of 180 (H), 150 (M) and 41 (L) kDa, are produced by
      alternative splicing of the pre-mRNA and are regulated differently during
      development. The three isoforms differ in their C-terminal tail domains, while
      their IF rod domains are identical. Synemins H/M occurred together with nestin
      and vimentin in glial progenitors during the early differentiation of the
      developing mouse central nervous system. They are later found in GFAP-labeled
      cells. In contrast, the L isoform appeared only in neurons, together with
      neurofilaments and betaIII-tubulin in the brain after birth. However, synemin L
      appeared from E13 in the peripheral nervous system, where it was confined to the
      neurons of spinal ganglia. In the meantime, the synemin H/M isoforms were found
      in both the neurons and Schwann cells of the sensorial ganglia from E11. Tissue
      fractionation and purification of IFs from adult mouse spinal cord revealed that
      the synemin L isoform binds to neurofilaments associated with the membrane
      compartment. This report describes the synthesis of the three synemin isoforms by
      selective cell types, and their temporal and spatial distributions. Mechanisms
      specific to neurons and glia probably control the splicing of the common synemin
      mRNA and the synthesis of each synemin isoform.

PMID- 16817201
TI  - Expression and function of calcium-activated potassium channels in human glioma
      cells.
AB  - Ca(2+)-activated K(+) (K(Ca)) channels are a unique family of ion channels
      because they are capable of directly communicating calcium signals to changes in
      cell membrane potential required for cellular processes including but not limited
      to cellular proliferation and migration. It is now possible to distinguish three
      families of K(Ca) channels based on differences in their biophysical and
      pharmacological properties as well as genomic sequence. Using a combination of
      biochemical, molecular, and biophysical approaches, we show that human tumor
      cells of astrocytic origin, i.e. glioma cells, express transcripts for all three
      family members of K(Ca) channels including BK, IK, and all three SK channel types
      (SK1, SK2, and SK3). The use of selective pharmacological inhibitors shows
      prominent expression of currents that are inhibited by the BK channel specific
      inhibitors iberiotoxin and paxilline. However, despite the presence of
      transcripts for IK and SK, neither clotrimazole, an inhibitor of IK channels, nor
      apamin, known to block most SK channels inhibited any current. The exclusive
      expression of functional BK channels was further substantiated by shRNA knockdown
      experiments, which selectively reduced iberiotoxin sensitive currents. Western
      blotting of patient biopsies with antibodies specific for all three KCa channel
      types further substantiated the exclusive expression of BK type KCa channels in
      vivo. This finding is in sharp contrast to other cancers that express primarily
      IK channels.

PMID- 16817203
TI  - Mineralization of hydroxyapatite in electrospun nanofibrous poly(L-lactic acid)
      scaffolds.
AB  - A highly porous electrospun poly(L-lactic acid) (PLLA) nanofibrous scaffold was
      used as a matrix for mineralization of hydroxyapatite. The mineralization process
      could be initiated by immersing the electrospun scaffold in the simulated body
      fluids (SBF) at 37 degrees C for varying periods of time. Scanning electron
      microscopy (SEM), energy-dispersive spectroscopy (EDS), wide-angle X-ray
      diffraction (WAXD), Fourier transform infrared (FTIR), and Raman spectroscopy
      were used to characterize the composition and the structure of the deposited
      mineral on the nanofiber surface. Results indicated that the mineral phase was a
      carbonated apatite with thin flake-like nanostructures. The effects of functional
      groups on the scaffold surface and anionic additives in the incubation fluids on
      the nucleation and growth of the mineral were investigated. It was found that a
      minuscule amount of anionic additives (e.g., citric acid and poly-L-aspartic
      acid) in the SBF could effectively inhibit the mineral growth. Surface
      modification of the scaffold was carried out by hydrolysis of PLLA scaffold in
      NaOH aqueous solution, where carboxylic acid groups were produced without
      compromising the scaffold integrity. The mineralization process from modified
      PLLA electrospun scaffolds was significantly enhanced because the calcium ions
      can bind to the carboxylate groups on the fiber surface.

PMID- 16817204
TI  - In vitro biocompatibility of a novel membrane of the composite poly(vinylidene
      trifluoroethylene)/barium titanate.
AB  - This study was aimed at investigating the in vitro biocompatibility of a novel
      membrane of the composite poly(vinylidene-trifluoroethylene)/barium titanate
      (P(VDF-TrFE)/BT). Osteoblastic cells were obtained from human alveolar bone
      fragments and cultured under standard osteogenic condition until subconfluence.
      First passaged cells were cultured on P(VDF-TrFE)/BT and expanded
      polytetrafluoroethylene (e-PTFE--control) membranes in 24-well plates. Cell
      adhesion and spreading were evaluated at 30 min, and 4 and 24 h. For
      proliferation assay, cells were cultured for 1, 7, and 10 days. Cell viability
      was detected by trypan blue at 7 and 10 days. Total protein content and alkaline
      phosphatase (ALP) activity were measured at 7, 14, and 21 days. Cultures were
      stained with Alizarin red at 21 days, for detection of mineralized matrix. Data
      were compared by ANOVA and Student t test. Cell attachment (p = 0.001), cell
      number (p = 0.001), and ALP activity (p = 0.0001) were greater on P(VDF-TrFE)/BT.
      Additionally, doubling time was greater on P(VDF-TrFE)/BT (p = 0.03), indicating
      a decreased proliferation rate. Bone-like nodule formation took place only on
      P(VDF-TrFE)/BT. The present results showed that both membranes are biocompatible.
      However, P(VDF-TrFE)/BT presented a better in vitro biocompatibility and allowed
      bone-like nodule formation. Therefore, P(VDF-TrFE)/BT could be an alternative
      membrane to be used in guided tissue regeneration.

PMID- 16817205
TI  - Validity of the 30-item geriatric depression scale in patients with Parkinson's
      disease.
AB  - Depression in Parkinson's disease (dPD) is difficult to diagnose because
      depressive symptoms can overlap with symptoms of Parkinson's disease (PD).
      Subject-rated scales such as the 30-item Geriatric Depression Scale (GDS) may be
      useful in screening for dPD. There were 57 patients (33 men, 24 women; mean age,
      58.6 years [SD +/- 8.4]) enrolled in a study of pallidotomy for intractable PD
      who were evaluated for depression before and after surgery. Subjects were
      evaluated using the 17-item Hamilton Depression Rating Scale (HDRS), Structured
      Clinical Interview for Diagnostic and Statistical Manual-III (SCID), and the GDS.
      SCID was used to diagnose major depression with confirmation by an expert
      geropsychiatrist. Receiver-operating curves (ROC) were used to identify cutoff
      points with maximal discriminant validity for diagnosing dPD. A total of 213
      evaluation time points were included for the 52 patients with time points that
      included a valid SCID diagnosis, GDS, and HDRS. A ROC established points of
      maximum specificity/sensitivity for the GDS at a cutoff of 9/10 (sensitivity =
      0.809, specificity = 0.837, positive predictive value [PPV] = 0.584, negative
      predictive value [NPV] = 0.939) and for the HDRS at a cutoff of 12/13
      (sensitivity = 0.810, specificity = 0.821, PPV = 0.580, NPV = 0.934). The GDS was
      moderately correlated with the HDRS (Pearson's r = 0.54; P < 0.001). The GDS is
      useful in screening for dPD. A cutoff score of 9/10 has acceptable discriminant
      validity for dPD, and the GDS has a moderate correlation with the HDRS in PD
      patients.

PMID- 16817206
TI  - P2X(7) receptors on microglial cells mediate injury to cortical neurons in vitro.
AB  - The P2X(7) receptor has been implicated in the release of cytokines and in the
      induction of cell death, and is up-regulated in a transgenic mouse model of
      Alzheimer's disease. Using cocultures of rat cortical neurons and microglia, we
      show that ATP and the more potent P2X(7) agonist benzoylbenzoyl-ATP (BzATP) cause
      neuronal cell injury. The deleterious effects of BzATP-treated microglia were
      prevented by nonselective P2X antagonists (PPADS and oxidized ATP) and by the
      more selective P2X(7) antagonist Brilliant Blue G. Similar concentrations of
      BzATP caused release of superoxide and nitric oxide from isolated microglia, and
      neuronal cell injury was attenuated by a superoxide dismutase mimetic and by a
      peroxynitrite decomposition catalyst, suggesting a role for reactive oxide
      species. Cocultures composed of wild-type cortical neurons, and microglia from
      P2X(7) receptor-deficient mice failed to exhibit neuronal cell injury in the
      presence of BzATP, but retained sensitivity to injury when microglia were derived
      from genotypically matched normal (P2X(7) (+/+) mice), thereby establishing
      P2X(7) involvement in the injury process. P2X(7) receptor activation on microglia
      thus appears necessary for microglial-mediated injury of neurons, and proposes
      that targeting P2X(7) receptors may constitute a novel approach for the treatment
      of acute and chronic neurodegenerative disorders where a microglial component is
      evident.

PMID- 16817207
TI  - Aripiprazole associated with severe exacerbation of Parkinson's disease.

PMID- 16817208
TI  - Effects of interconnecting porous structure of hydroxyapatite ceramics on
      interface between grafted tendon and ceramics.
AB  - The purpose of this study was to evaluate histologically and biomechanically the
      interface between porous hydroxyapatite ceramics and a tendon grafted into
      ceramics, and to compare the interface in two ceramics with different porous
      structures: interconnected porous calcium hydroxyapatite ceramics (IP-CHA) with
      an effective porosity index (interpore diameter > 20 microm) of 63.6%, and porous
      calcium hydroxyapatite ceramics with less interconnection (HA-L) with an
      effective porosity index of 5.5%. The tendon-IP-CHA complex and the tendon-HA-L
      complex were implanted into the bone defects made in both knees of rabbits. With
      IP-CHA, abundant fibrous tissue, including vessels and collagen fiber continuity,
      was observed inside interface-region pores. The amount of osseous tissue in
      interface-region pores increased over time, and at 24 weeks after operation, the
      tendon was in direct contact with the osseous tissue in IP-CHA. With HA-L, the
      amount of fibrous tissue in interface-region pores was low and did not increase.
      The results of biomechanical analysis revealed that the maximum tendon pull-out
      load from IP-CHA was significantly higher than that from HA-L. With the porous
      hydroxyapatite ceramics having highly interconnecting porous structure, a
      bioactive interface was achieved between ceramics and grafted tendon. On the
      basis of these results, we conclude that bone defects, including tendon
      insertion, can be reconstructed using IP-CHA.

PMID- 16817209
TI  - Strain patterns during tensile, compressive, and shear fatigue of human cortical
      bone and implications for bone biomechanics.
AB  - It is a common theme in basic bone biomechanics and in biomechanical applications
      that much of the behavior can be determined and is dictated by the level of
      strain, whether this pertains to bone physiology, bone remodeling,
      osseoinduction, osseointegration, or the development of damage. The development
      of damage, demonstrated by stiffness loss measurements, has already been reported
      in detail in the literature. However, the systematic study of the development of
      "plastic" (residual) strains, which are associated with the inelastic mechanical
      behavior of bone tissue, has generally been overlooked. The present study
      compares the rates at which the elastic (e(a)) and plastic components (e(p)) of
      strain developed during tensile, compressive, and shear fatigue in human cortical
      bone of six individuals aged between 53 and 79 years. The overall hypothesis of
      this investigation is that there is a common underlying factor in the damage
      related behavior of bone, which may allow us to link together the various aspects
      of the damage related behavior of bone. The rate of development of plastic strain
      (Deltae(p)/DeltaN) and the rate of growth in elastic strain amplitude
      (Deltae(a)/DeltaN) are described as a function of the stress (sigma), and/or
      stress normalized by the modulus of elasticity (sigma/E). The implications of our
      findings are discussed with respect to simple models/mechanisms, which may
      underlie the observed behavior.

PMID- 16817210
TI  - Calcium carbonate-calcium phosphate mixed cement compositions for bone
      reconstruction.
AB  - The feasibility of making calcium carbonate-calcium phosphate (CaCO(3)-CaP) mixed
      cements, comprising at least 40% (w/w) CaCO(3) in the dry powder ingredients, has
      been demonstrated. Several original cement compositions were obtained by mixing
      metastable crystalline CaCO(3) phases with metastable amorphous or crystalline
      CaP powders in aqueous medium. The cements set within at most 1 h at 37 degrees C
      in atmosphere saturated with water. The hardened cement is microporous and
      exhibits weak compressive strength. The setting reaction appeared to be
      essentially related to the formation of a highly carbonated nanocrystalline
      apatite phase by reaction of the metastable CaP phase with part or almost all of
      the metastable CaCO(3) phase. The recrystallization of metastable CaP varieties
      led to a final cement consisting of a highly carbonated poorly crystalline
      apatite analogous to bone mineral associated with various amounts of vaterite
      and/or aragonite. The presence of controlled amounts of CaCO(3) with a higher
      solubility than that of the apatite formed in the well-developed CaP cements
      might be of interest to increase resorption rates in biomedical cement and favors
      its replacement by bone tissue. Cytotoxicity testing revealed excellent
      cytocompatibility of CaCO(3)-CaP mixed cement compositions.

PMID- 16817211
TI  - Biomineralization of polyanionic collagen-elastin matrices during cavarial bone
      repair.
AB  - The polyanionic collagen-elastin matrices (PCEMs) are osteoconductive scaffolds
      that present high biocompatibility and efficacy in the regeneration of bone
      defects. In this study, the objective was to determine if these matrices are
      directly mineralized during the osteogenesis process and their influence in the
      organization of the new bone extracellular matrix. Samples of three PCEMs,
      differing in their charge density, were implanted into critical-sized calvarial
      bone defects created in rats and evaluated from 3 days up to 1 year after
      implantation. The implanted PCEMs were directly biomineralized by osteoblasts as
      shown by ultrastructural, histoenzymologic, and morphologic analysis. The removal
      of the implants occurred during the bone remodeling process. The organization of
      the new bone matrix was evaluated by image texture analysis determining the
      Shannon's entropy and the fractal dimension of digital images. The bone matrix
      complexity decreased as the osteogenesis progressed approaching the values
      obtained for the original bone structure. These results show that the PCEMs allow
      faster formation of new bone by direct biomineralization of its structure and
      skipping the biomaterial resorption phase.

PMID- 16817212
TI  - Global gene expression analysis of the effects of vinblastine on endothelial
      cells, when eluted from a thermo-responsive polymer.
AB  - In-stent restenosis remains a significant problem associated with bare metal
      stents. This drawback has prompted research into improving stent design and the
      development of novel coatings, including drug-eluting stents. A number of drug
      eluting stents are currently on the market; however, the success rate of these
      stents in complex situations has been found to be quite low. Thus, there remains
      potential for the development of more suitable drug-eluting stents. The aims of
      this study were to use a thermoresponsive polymer to develop a system to locally
      deliver vinblastine, an antimitotic agent currently used as an anticancer drug,
      and in addition, assess the effects of this drug at the gene expression level in
      vitro. An N-isopropylacrylamide/N-tert-butylacrylamide (NiPAAm/NtBAAm) copolymer
      solution in the ratio 65:35 was prepared and appropriate volumes of vinblastine
      were added to generate two final drug concentrations of 22 nanomoles/film or
      0.022 nanomoles/film. Stainless steel discs (316) were coated with the copolymer
      solution or this solution containing drug. Human endothelial cells were cultured
      on collagen type 1 gels and then incubated with the coated discs for 24 h. Gene
      expression studies using oligonucleotide microarray analysis and quantitative RT
      PCR were then performed. Microarray analysis revealed that vinblastine causes the
      differential expression of a range of genes involved in a variety of different
      functions, including cell cycle and apoptosis. The changes in expression of some
      of these genes culminate in cell cycle arrest and apoptotic pathways.

PMID- 16817214
TI  - Mating biology of the leaf-cutting ants Atta colombica and A. cephalotes.
AB  - Copulation behavior has often been shaped by sexually selected sperm competition
      or cryptic female choice. However, manipulation of previously deposited
      ejaculates is unknown in the social Hymenoptera and the degree to which sperm
      competes after insemination or is actively selected by females has remained
      ambiguous. We studied the mating process in the leaf-cutting ants Atta colombica
      and A. cephalotes, which belong to one of the few derived social insect lineages
      where obligate multiple mating has evolved. As copulations often occur at night
      and in remote places, direct observations were impossible, so we had to
      reconstruct the sequential copulation events by morphological analysis of the
      male and female genitalia and by tracking the process of sperm transfer and sperm
      storage. We show that Atta male genitalia have two external rows of spiny teeth,
      which fit into a specialized pouch organ in the female sexual tract.
      Reconstruction of the sperm storage process indicated that sperm is transferred
      to the spermatheca during or immediately after ejaculation and without being
      mixed with sperm and seminal fluids from other males. A convergent mechanism of
      direct sperm transfer to the spermatheca of queens is known from two species of
      dwarf honeybees. Direct sperm transfer may restrict female control over the sperm
      storage process and the number of males that contribute to the stored sperm.

PMID- 16817213
TI  - A case of dysferlinopathy presenting choreic movements.
AB  - Mutations in the dysferlin gene cause limb-girdle muscular dystrophy type 2B
      (LGMD2B). The involvement of the central nervous system in dysferlinopathy has
      not been described. We describe the clinical features of a patient with LGMD2B
      associated with dysferlin mutations (homozygous G3370T) who presented progressive
      choreic movements. The patient had no evidence of other causes of chorea. It is
      suggested that the chorea may be associated with the altered expression of the
      brain isoform of dysferlin.

PMID- 16817215
TI  - Cobalt and chromium ions induce nitration of proteins in human U937 macrophages
      in vitro.
AB  - The in situ localization of nitrotyrosine, a product of the nitration of tyrosine
      residues by peroxynitrite, in the interface membranes from Co--Cr--Mo and Ti--Al-
      V prostheses provided evidence of nitric oxide-induced oxidative damage in the
      periprosthetic environment. In the present study, we compared the effects of
      different wear products from hip prostheses on the nitration of proteins in
      macrophages in vitro. Nitration of proteins was measured by Western blot using a
      polyclonal antibody directed against nitrotyrosines. Results showed that Co(2+)
      and Cr(3+) ions induced the nitration of a 79 +/- 4 kDa protein in a time- and
      dose-dependent manner. Indeed, the stimulation was significant (p < 0.05) after
      24 h with 10 ppm Co(2+) and reached a plateau level between 48 and 72 h. With
      Cr(3+), the stimulation was significant (p < 0.05) only after 48 and 72 h. The
      effect of both Co(2+) and Cr(3+) ions was inhibited by glutathione monoethyl
      ester that provides protection against oxidative stress. However, ultrahigh
      molecular-weight-polyethylene and alumina ceramic particles had no significant
      effect on the nitration of proteins. Finally, the results showed that nitrated
      proteins are mainly found in the cytoplasmic fraction of cells and are absent
      from the nucleus. In conclusion, our results show that Co(2+) and Cr(3+) ions
      induce the nitration of cytoplasmic proteins in human U937 macrophages,
      suggesting that metal ions from MM prostheses have the potential to modify
      protein function in the periprosthetic environment and in circulating cells.

PMID- 16817216
TI  - Novel nerve guidance material prepared from bovine aponeurosis.
AB  - Spinal cord injury (SCI) creates an adverse environment for axon regeneration. As
      a result, the axons at the injury sites begin to be atrophy, retract and lose
      their functions. Several strategies to promote axon regeneration at the injury
      site have been tested, but the progress is very limited. One of the major reasons
      is that the regenerated axons often extend randomly and do not reach the proper
      place. Fabricating linearly ordered materials as nerve guidance would be
      important to solve such problems. In this study, a novel type of nerve guidance
      material was prepared from the bovine aponeurosis, which mainly consisted of
      ordered collagen fibers. The processed material showed good cell compatibility
      and low immunogenisity. Moreover, the processed material guided the neurites
      outgrowth of in vitro cultured cortical neurons along its fibers. The results
      suggested that the processed aponeurosis would be a proper nerve guidance
      biomaterial for SCI repair.

PMID- 16817217
TI  - Host inflammatory response to NiCr, CoCr, and Ti in a soft tissue implantation
      model.
AB  - The inflammatory response to nickel chromium (NiCr), cobalt chromium (CoCr), and
      titanium (Ti) implants at 7 and 28 days was investigated using real-time PCR
      analysis along with histological and immunohistochemical staining. Contrasting
      inflammatory profiles were found in response to the different metal compositions.
      The inflammatory profile induced by CoCr remained consistent and elevated during
      the 28-day period with high cell counts associated with the implants and a
      progressive recruitment of T lymphocytes. The response to NiCr was also elevated,
      but with an initially low T-lymphocyte infiltration that increased by the later
      time period. Ti indicated an early increased inflammatory response that had
      reduced by 28 days. Changes in gene expression demonstrated that Ti induced very
      low levels of expression of the three inflammatory cytokine genes. NiCr initiated
      a significant upregulation in gene expression for IL-6 and TNF-alpha. CoCr
      resulted in the highest upregulation of IL-2 indicative of T-lymphocyte
      activation to this material.

PMID- 16817218
TI  - Macrophage-mediated biodegradation of poly(DL-lactide-co-glycolide) in vitro.
AB  - Biodegradation of poly-DL-lactide-co-glycolide (PLGA) both in vitro and in vivo
      has been well documented. However, the roles that macrophages and their fused
      multinucleated giant cells (MNGCs) play in this biodegradation are still unclear.
      The current study aimed to investigate macrophage-mediated biodegradation of PLGA
      thin films and of PLGA composites with hydroxyapatite (HA) and tricalcium
      phosphate (TCP) ceramic powders in vitro using a murine macrophage cell line (RAW
      264.7). The interactions were analyzed by using cell viability assays, scanning
      electron microscopy, and focused ion beam microscopy. The results showed that RAW
      264.7 cells effectively attached and proliferated on the PLGA films and PLGA-HA,
      PLGA-TCP composites. The RAW 264.7 cells were observed to aggregate and fuse to
      form MNGCs. The cell processes on the membrane, or pseudopodia, penetrated into
      the PLGA films and evidently eroded the surface. We conclude that macrophages and
      fused MNGCs actively respond to PLGA films as substratum and degrade the surface
      of this polymer.

PMID- 16817219
TI  - Fracture toughness estimation for the TMJ disc.
AB  - J contour integral fracture toughness of the temporomandibular (TMJ) disc was
      estimated from a computational model based on fracture load data derived from
      experimental tests. The computational model involved a stress analysis of TMJ
      disc specimens with cracks oriented parallel and perpendicular to the primary
      collagen fiber axis within the intermediate zone of the disc. The results
      demonstrated differences occurred between crack orientations when an orthotropic
      model was used. Fracture toughness was much lower for a crack oriented parallel
      to the collagen fiber direction than that for a crack oriented perpendicularly.
      Thickness, crack size, and anisotropy ratio were observed as additional variables
      affecting the fracture toughness of the TMJ disc. Future model enhancements may
      be achieved by considering the poroviscoelastic nature of the TMJ disc.

PMID- 16817220
TI  - Using single-walled carbon nanotubes nonwoven films as scaffolds to enhance long
      term cell proliferation in vitro.
AB  - Carbon nanotubes have attracted intensive interests in biomedical research in
      recent years. In this study, a novel type of carbon nanotubes material so called
      nonwoven single-walled carbon nanotubes (SWNTs) with nanotopographic structure
      and macroscopic volume was used as cell growing scaffold. The morphology and
      surface chemistry of nonwoven SWNTs were observed and characterized through
      scanning electron microscopy and X-ray photoelectron spectroscopy, respectively.
      The cells were cultivated in nonwoven SWNTs and in other types of substrate as
      control. The cells growth behaviors including adhesion, proliferation, and
      cytoskeletal development was investigated by using cell viability assay and
      confocal observation. The experimental results indicated that nonwoven SWNTs
      exhibited significant enhancement to the cells adhesion and proliferation in at
      least 3 weeks. Numerous and highly organized cytoskeletal structures were
      observed when the cells were cultured in nonwoven SWNTs. Furthermore, an obvious
      promotional influence of the cells cultivated in nonwoven SWNTs scaffold upon the
      proliferation of those growing in the other kind of substrate through cell-cell
      communication had been found. The results obtained in this work are of
      significance to in vitro cell amplification in large scale, tissue regeneration,
      or guided repair, as well as biomedical device application.

PMID- 16817221
TI  - Substrate mineralization stimulates focal adhesion contact redistribution and
      cell motility of bone marrow stromal cells.
AB  - Understanding the mechanisms of substrate based control of cell function is
      critical to the design of biomaterials. Cells interact with their extracellular
      matrix through cell adhesion contacts. We have previously described the self
      assembly of bone-like mineral onto an organic template and have shown that these
      biomimetic surfaces lead to an increased volume fraction of bone regenerated in
      vivo. In the present study, we compared the distribution of cell adhesion
      contacts, cell spreading, and cell motility of murine bone marrow stromal cells
      (BMSC) on mineralized vs. nonmineralized substrates. We developed a new approach
      for quantification of cell-material interactions and demonstrated that cell
      adhesion contacts on mineralized substrates were distributed throughout the cell
      surface contacting the substrate, whereas on nonmineralized substrates cell
      adhesion contacts were present near the cell periphery. We propose that
      mineralized substrates stimulate the predominant expression of fibrillar
      contacts, and nonmineralized substrates stimulate expression of focal adhesion
      contacts. Cell motility assays with colloidal gold demonstrated a statistically
      significant decrease in the average phagokinetic index of migrating cells on
      mineralized vs. nonmineralized substrates after 90 min of cell seeding. We
      propose that the physical-chemical properties of the substrate, altered by
      mineralization, cause expression of specific types of cell contacts and, as a
      result, modify molecular mechanisms responsible for cell spreading, motility, and
      possibly differentiation.

PMID- 16817222
TI  - Comparison of aortic valve allograft decellularization techniques in the rat.
AB  - Rodent models have been essential to understanding the immune-mediated failure of
      aortic valve allografts (AVAs). Decellularization has been proposed to reduce the
      immunogenicity of AVAs. The objective of this study was to determine the most
      effective method to decellularize AVAs for use in a rat model. Three different
      decellularization techniques were compared in Lewis aortic valves. Detergent
      decellularization involved a series of hypotonic and hypertonic Tris buffers at 4
      degrees C for 48 h/buffer containing 0.5% Triton X-100 followed by a 72 h washout
      in phosphate-buffered saline. Osmotic decellularization was performed in similar
      manner to the detergent-based technique except without the addition of Triton X
      100. Enzymatic decellularization consisted of trypsin/EDTA at 37 degrees C for 48
      h. Assessment was performed with light microscopy (H&E, Movat's pentachrome),
      immunohistochemistry for residual cellular elements, and hydroxyproline assays.
      Detergent-based methodology effected near-complete decellularization of both the
      leaflets and aortic wall in addition to preservation of the extracellular matrix
      (ECM). Osmotic lysis was associated with preservation of ECM and moderate
      decellularization. Enzymatic decellularization resulted in complete
      decellularization but extensive degeneration and fragmentation of the ECM. When
      implanted into the infrarenal aorta of allogeneic rats for 1 week, valves
      decellularized with detergent-based and osmotic methodology failed to stimulate
      an allogeneic immune response as evidenced by an absence of T cell infiltrates.
      Osmotic lysis protocols with low dose detergent appear to be most effective at
      both removing antigenic cellular elements and preserving ECM.

PMID- 16817224
TI  - Centrosome function in normal and tumor cells.
AB  - Centrosomes nucleate microtubules that form the mitotic spindle and regulate the
      equal division of chromosomes during cell division. In cancer, centrosomes are
      often found amplified to greater than two per cell, and these tumor cells
      frequently have aneuploid genomes. In this review, we will discuss the cellular
      factors that regulate the proper duplication of the centrosome and how these
      regulatory steps can lead to abnormal centrosome numbers and abnormal mitoses. In
      particular, we highlight the newly emerging role of the Breast Cancer 1 (BRCA1)
      ubiquitin ligase in this process.

PMID- 16817223
TI  - The scale of substratum topographic features modulates proliferation of corneal
      epithelial cells and corneal fibroblasts.
AB  - The cornea is a complex tissue composed of different cell types, including
      corneal epithelial cells and keratocytes. Each of these cell types are directly
      exposed to rich nanoscale topography from the basement membrane or surrounding
      extracellular matrix. Nanoscale topography has been shown to influence cell
      behaviors, including orientation, alignment, differentiation, migration, and
      proliferation. We investigated whether proliferation of SV40-transformed human
      corneal epithelial cells (SV40-HCECs), primary human corneal epithelial cells
      (HCECs), and primary corneal fibroblasts is influenced by the scale of
      topographic features of the substratum. Using basement membrane feature sizes as
      our guide and the known dimensions of collagen fibrils of the corneal stroma (20
      60 nm), we fabricated polyurethane molded substrates, which contain anisotropic
      feature sizes ranging from 200-2000 nm on pitches ranging from 400 to 4000 nm
      (pitch = ridge width + groove width). The planar regions separating each of the
      six patterned regions served as control surfaces. Primary corneal and SV40-HCEC
      proliferation decreased in direct response to decreasing nanoscale topographies
      down to 200 nm. In contrast to corneal epithelial cells, corneal fibroblasts did
      not exhibit significantly different response to any of the topographies when
      compared with planar controls at 5 days. However, decreased proliferation was
      observed on the smallest feature sizes after 14 days in culture. Results from
      these experiments are relevant in understanding the potential mechanisms involved
      in the control of proliferation and differentiation of cells within the cornea.

PMID- 16817225
TI  - Involvement of caspase activation and mitochondrial stress in trichostatin A
      induced apoptosis of Burkitt's lymphoma cell line, Akata.
AB  - Epstein-Barr virus (EBV) infects more than 90% of the human population and has a
      potential oncogenic nature. Trichostatin A (TSA) has potent antitumor activity,
      but its exact mechanism on EBV-infected cells is unclear. This study examined the
      effects of TSA on proliferation and apoptosis of the Burkitt's lymphoma cell
      line, Akata. TSA treatment inhibited cell growth and induced cytotoxicity in both
      the EBV-negative and -positive Akata cells. TSA sensitively induced apoptosis in
      both cells, as demonstrated by the increased number of positively stained cells
      in the TUNEL assay, the migration of many cells to sub-G1 phase by flow
      cytometric analysis, and the formation of DNA ladders. This suggests that EBV has
      no effect on the sensitivity to TSA. Western blot analysis showed that the
      cleavage of PARP and Bid and the activation of caspases are closely related to
      the TSA-induced apoptosis of the cells. The reduction in mitochondrial transition
      potential and the release of apoptosis-inducing factor from mitochondria to
      cytosol was also observed after the TSA treatment, but was suppressed by treating
      the cells with a cathepsin B inhibitor. Overall, these findings suggest that
      besides the caspase-dependent pathway, mitochondrial events are also associated
      with the TSA-induced apoptosis of Akata cells.

PMID- 16817226
TI  - Transcriptional regulation of the homeobox gene NKX3.1 by all-trans retinoic acid
      in prostate cancer cells.
AB  - NKX3.1 is a homeobox gene, expression of which is largely restricted to the adult
      prostatic epithelium. Loss of NKX3.1 expression has been linked to prostate
      carcinogenesis and disease progression and occurs in the absence of mutations in
      the coding region of the NKX3.1 gene. In this study, we have characterized
      regulation of NKX3.1 expression by all-trans retinoic acid (tRA), a naturally
      occurring vitamin A metabolite that is accumulated at high levels in the
      prostate. Using the prostate cancer cell line LNCaP, Western blot analysis
      revealed a approximately twofold induction of NKX3.1 protein levels following tRA
      exposure, with sequential analysis of NKX3.1 protein levels in cycloheximide co
      treated cells indicating that tRA does not alter NKX3.1 protein turnover. The
      approximately 1.6-fold increase in NKX3.1 mRNA levels detected in tRA-treated
      LNCaP cells also occurred independently of new protein synthesis and was not
      mediated by changes in NKX3.1 mRNA stability. In contrast, nuclear run-on assays
      indicated that tRA treatment increased NKX3.1 transcription. To identify retinoid
      responsive regions of the NKX3.1 gene, DNA sequences encompassing approximately 2
      kb of the NKX3.1 promoter or the entire 3'untranslated region (UTR) were cloned
      into luciferase reporter plasmids. Analysis of induced luciferase activity
      following transfection of these constructs into prostate cancer cells did not
      identify tRA responsiveness, however the 3'UTR was found to be strongly androgen
      responsive. These studies demonstrate that the NKX3.1 gene is a direct target of
      retinoid receptors and suggest that androgen regulation of NKX3.1 expression is
      mediated in part by the 3'UTR.

PMID- 16817227
TI  - The effects of a mutant p53 protein on the proliferation and differentiation of
      PC12 rat phaeochromocytoma cells.
AB  - PC12 rat phaeochromocytoma cells show neuronal differentiation upon NGF
      treatment. NGF induces prolonged activation of the Ras/Raf/MEK/ERK pathway in
      which the 42/44 kDa mitogen-activated protein kinases (MAPKs), ERK 1 and 2 are
      thought to be the key mediators of the differentiation signals. Activation of
      ERKs leads to the increased transcription of early response genes resulting in
      cell cycle arrest. Upon NGF treatment the p53 protein, the most commonly mutated
      tumor suppressor in human cancers, translocates to the nucleus and may play a
      role in the mediation of NGF-induced cell cycle arrest and neuronal
      differentiation. Here we demonstrate that in PC12 cells expressing both wild-type
      and V143A mutant p53 proteins (p143p53PC12 cells), p53-mediated biological
      responses are critically influenced. p143p53PC12 cells are not able to cease
      their proliferation and begin their neuronal differentiation program upon NGF
      treatment. The presence of mutant p53 also reduces the DNA-binding activity of
      endogenous p53 and disturbs the regulatory machinery of p53 including both the
      phosphorylation of ERK 1/2, p38 and SAPK/JNK MAP kinases and itself.

PMID- 16817228
TI  - Functional regression analysis using an F test for longitudinal data with large
      numbers of repeated measures.
AB  - Longitudinal data sets from certain fields of biomedical research often consist
      of several variables repeatedly measured on each subject yielding a large number
      of observations. This characteristic complicates the use of traditional
      longitudinal modelling strategies, which were primarily developed for studies
      with a relatively small number of repeated measures per subject. An innovative
      way to model such 'wide' data is to apply functional regression analysis, an
      emerging statistical approach in which observations of the same subject are
      viewed as a sample from a functional space. Shen and Faraway introduced an F test
      for linear models with functional responses. This paper illustrates how to apply
      this F test and functional regression analysis to the setting of longitudinal
      data. A smoking cessation study for methadone-maintained tobacco smokers is
      analysed for demonstration. In estimating the treatment effects, the functional
      regression analysis provides meaningful clinical interpretations, and the
      functional F test provides consistent results supported by a mixed-effects linear
      regression model. A simulation study is also conducted under the condition of the
      smoking data to investigate the statistical power for the F test, Wilks'
      likelihood ratio test, and the linear mixed-effects model using AIC.

PMID- 16817229
TI  - Phosphatidylinositol 3-kinase/Akt auto-regulates PDGF-BB-stimulated interleukin-6
      synthesis in osteoblasts.
AB  - It has been reported that platelet-derived growth factor (PDGF)-BB stimulates the
      synthesis of interleukin (IL)-6 in osteoblasts. In the present study, we
      investigated whether the phosphatidylinositol 3-kinase (PI3K)/Akt is involved in
      the PDGF-BB-induced IL-6 synthesis in osteoblast-like MC3T3-E1 cells. PDGF-BB
      markedly induced the phosphorylation of Akt and GSK-3beta. Akt inhibitor, 1L-6
      hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate,
      significantly amplified the synthesis of IL-6 by PDGF-BB. The PDGF-BB-induced GSK
      3beta phosphorylation was suppressed by the Akt inhibitor. The IL-6 synthesis
      stimulated by PDGF-BB was markedly enhanced by LY294002 and wortmannin,
      inhibitors of PI3K. Wortmannin and LY294002 suppressed the PDGF-BB-induced
      phosphorylation of Akt and GSK-3beta. Taken together, these results strongly
      suggest that PI3K/Akt negatively regulates the PDGF-BB-stimulated IL-6 synthesis
      in osteoblasts.

PMID- 16817230
TI  - Overexpression of regucalcin enhances glucose utilization and lipid production in
      cloned rat hepatoma H4-II-E cells: Involvement of insulin resistance.
AB  - The role of regucalcin, which is a regulatory protein in intracellular signaling
      pathway, in the regulation of glucose utilization and lipid production was
      investigated using the cloned rat hepatoma H4-II-E cells overexpressing
      regucalcin. The hepatoma cells (wild-type) and stable regucalcin/pCXN2
      transfected cells (transfectant) were cultured for 72 h in a medium containing
      10% fetal bovine serum (FBS) to obtain subconfluent monolayers. Cells with
      subconfluency were cultured for 24 or 72 h in medium containing either vehicle or
      insulin (10(-8) or 10(-7) M) with or without supplementation of glucose (10, 25,
      or 50 mg/ml of medium) in the absence of insulin. The production of triglyceride
      and free fatty acid was significantly increased in transfectants cultured without
      insulin and glucose supplementation as compared with that of wild-type cells. The
      supplementation of glucose (10, 25, or 50 mg/ml) caused a remarkable increase in
      medium glucose consumption, triglyceride, and free fatty acid productions in
      transfectants cultured without insulin. The presence of insulin (10(-7) M) caused
      a significant increase in medium glucose consumption, triglyceride, and free
      fatty acid productions in wild-type cells cultured with glucose supplementation.
      These increases were significantly prevented in transfectants cultured for 72 h.
      The expression of acetyl-CoA carboxylase, HMG-CoA reductase, glucokinase,
      pyruvate kinase, and glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) mRNAs in
      wild-type cells was not significantly changed by culture with or without glucose
      supplementation in the presence of insulin. These gene expressions were not
      significantly changed in transfectants. The expression of glucose transporter 2
      mRNA was significantly increased in transfectants as compared with that of wild
      type cells. Such an increase was not seen in transfectants cultured in the
      presence of insulin with or without glucose supplementation. This study
      demonstrates that overexpression of regucalcin enhances glucose utilization and
      lipid production in the cloned rat hepatoma H4-II-E cells, and that it regulates
      the effect of insulin.

PMID- 16817231
TI  - Biological activity of rainbow trout Ea4-peptide of the pro-insulin-like growth
      factor (pro-IGF)-I on promoting attachment of breast cancer cells (MDA-MB-231)
      via alpha2- and beta1-integrin.
AB  - E-peptide of pro-IGF-I was considered as biologically inactive. We have
      demonstrated that rainbow trout (rt) Ea4-peptide exerted biological activities in
      several established tumor cell lines [Chen et al., 2002; Kuo and Chen, 2002].
      Here we report the activity of rtEa4-peptide in promoting attachment of human
      breast cancer cells (MDA-MB-231). While rtEa2-, rtEa3-, and rtEa4-peptides
      enhanced the attachment of MDA-MB-231 cells in a dose dependent manner, rtEa4
      peptide possessed the highest activity. Antibodies specific to alpha2 and beta1
      integrins significantly inhibited the attachment of cells to rtEa4-peptide coated
      plates by 40%. In addition, rtEa4-peptide induced the expression of fibronectin 1
      and laminin receptor genes in MDA-MB-231 cells. Blocking new protein synthesis by
      cycloheximide significantly reduced the attachment of MDA-MB-231 cells to rtEa4
      peptide coated wells by 50%. These results suggest that rtEa4-peptide may promote
      cell attachment by interacting with alpha2/beta1 integrin receptors at the cell
      surface and by inducing the expression of fibronectin 1 and laminin receptor
      genes. Expression of fibronectin 1 gene induced by rtEa4-peptide in MDA-MB-231
      cells was abolished by inhibitors of PI3K, PKC, Mek1/2, JNK1/2, and p38 MAPK
      signaling transduction molecules. These results suggested that induction of
      fibronectin 1 gene expression in MDA-MB-231 cells by rtEa4-peptide may be
      mediated via PI3K, PKC, Mek1/2, JNK1/2, and p38 MAPK signal transduction
      molecules.

PMID- 16817232
TI  - Functional analysis of CBP/p300 in embryonic orofacial mesenchymal cells.
AB  - CREB binding protein (CBP) and the close structural homolog, p300, are nuclear
      coactivators of multiple signaling pathways that play important roles in
      embryonic development and cellular homeostasis. TGFbeta regulates the
      proliferation rate of many cell types and has been demonstrated to inhibit the
      growth rate of mouse embryonic maxillary mesenchymal (MEMM) cells. The role of
      CBP and p300 in TGFbeta-mediated control of proliferation of MEMM cells was thus
      investigated using an in vitro gene knockdown approach. TGFbeta reporter assays
      demonstrated that p300 mRNA knockdown via targeted siRNAs led to a reduction in
      the response to TGFbeta, whereas knockdown of CBP by the same approach had an
      insignificant effect. In MEMM cell proliferation assays, siRNA-mediated knockdown
      of CBP and/or p300 had little impact upon TGFbeta-mediated growth inhibition;
      however, the basal rate of proliferation was increased. Inhibition of p300
      activity via overexpression of a dominant-negative mutant (p300deltaC/H3) led to
      significant inhibition of TGFbeta-mediated activation of p3TP-lux. As with the
      siRNA knockdown approach, p300deltaC/H3 also increased the basal rate of cell
      proliferation of MEMM cells. CBP/p300 siRNA knockdown had a significant but
      incomplete inhibition of TGFbeta-induction of matrix metalloproteinase-9
      (gelatinase B) expression. These data demonstrate that p300 is involved in Smad
      mediated transcription of p3TP-lux, however, its role (and that of CBP) in
      biological processes such as the control of cell proliferation and extracellular
      matrix metabolism is more complex and may be mediated via mechanisms beyond
      coactivator recruitment.

PMID- 16817233
TI  - Conformational changes of the p53-binding cleft of MDM2 revealed by molecular
      dynamics simulations.
AB  - Two 35-ns molecular dynamics simulations of both ligated [mouse double minute
      protein 2 (MDM2(p53))] and unligated (MDM2(apo)) structures of human MDM2 bound
      to the N-terminal domain of the tumor suppressor p53 have been performed.
      Analysis of the dynamics revealed that the most flexible region of MDM2 was the
      p53-binding cleft. When MDM2 was bound to p53, a wider and more stable topology
      of the cleft was obtained, while unligated MDM2 showed a narrower and highly
      flexible cleft. It was also found that the dynamics involved in the
      opening/closing motions were due to the movement of different domains of the
      protein, which is in agreement with recent experimental data. Considering our
      results, a mechanism in which p53 might be recognized and attached to MDM2 is
      proposed, and some implications on future directions for in silico anticancer
      drug design efforts are discussed. In summary, the observations made here would
      be very useful not only for better understanding of the biological implications
      of the MDM2 dynamics, but also for future efforts in anticancer drug design and
      discovery.

PMID- 16817234
TI  - Differential effects of matrix and growth factors on endothelial and fibroblast
      motility: application of a modified cell migration assay.
AB  - Cell migration is crucial in virtually every biological process and strongly
      depends on the nature of the surrounding matrix. An assay that enables real-time
      studies on the effects of defined matrix components and growth factors on cell
      migration is not available. We have set up a novel, quantitative migration assay,
      which enables unharmed cells to migrate along a defined matrix. Here, we used
      this so-called barrier-assay to define the contribution of fibronectin (FN) and
      Collagen-I (Col-I) to vascular endothelial growth factor (VEGF), basic fibroblast
      growth factor (bFGF), and lysophosphatidic acid (LPA)-induced cell migration of
      endothelial cells (EC) and fibroblasts. In EC, both FN and Col-I stimulated
      migration, but FN-induced motility was random, while net movement was inhibited.
      Addition of bFGF and VEGF overcame the effect of FN, with VEGF causing
      directional movement. In contrast, in 3T3 fibroblasts, FN stimulated motility and
      this effect was enhanced by bFGF. This motility was more efficient and
      morphologically completely different compared to LPA stimulation. Strikingly,
      directional migration of EC was not paralleled by higher amounts of stable
      microtubules (MT) or an increased reorientation of the microtubule-organizing
      centre (MTOC). For EC, the FN effect appeared concentration dependent; high FN
      was able to induce migration, while for fibroblasts both low and high
      concentrations of FN induced motility. Besides showing distinct responses of the
      different cells to the same factors, these results address contradictive reports
      on FN and show that the interplay between matrix components and growth factors
      determines both pattern and regulation of cell migration. J. Cell. Biochem. 99:
      1536-1552, 2006. (c) 2006 Wiley-Liss, Inc.

PMID- 16817235
TI  - In vivo modulation of epidermal growth factor receptor phosphorylation in mice
      expressing different gangliosides.
AB  - We studied in this work the in vivo phosphorylation of the epidermal growth
      factor receptor (EGFr) in skin from knockout mice lacking different ganglioside
      glycosyltransferases. Results show an enhancement of EGFr phosphorylation, after
      EGF stimulation, in skin from Sial-T2 knockout and Sial-T2/GalNAc-T double
      knockout mice as compared with wild-type and Sial-T1 knockout mice. Qualitative
      analysis of ganglioside composition in mice skin suggest that the increase of
      EGFr phosphorylation observed in skin from Sial-T2 knockout and Sial-T2/GalNAc-T
      double knockout mice in response to EGF might not be primary attributed to the
      expression of GD3 or a-series gangliosides in mice skin. These studies provide,
      for the first time, an approach for studying the molecular mechanisms involved in
      the in vivo regulation of EGFr function by gangliosides.

PMID- 16817236
TI  - Mechanism of 24,25-dihydroxyvitamin D3-mediated inhibition of rapid, 1,25
      dihydroxyvitamin D3-induced responses: role of reactive oxygen species.
AB  - In intestine, 24,25(OH)(2)D(3), which is made under conditions of calcium-,
      phosphate-, and 1,25(OH)(2)D(3) sufficiency, inhibits the stimulatory actions of
      1,25(OH)(2)D(3) on phosphate and calcium absorption. In the current work, we
      provide evidence that 24,25(OH)(2)D(3)-mediated signal transduction occurs
      mechanistically through increased H(2)O(2) production which involves binding of
      24,25(OH)(2)D(3) to catalase and resultant decreases in enzyme activity.
      Physiological levels of H(2)O(2) mimicked the action of 24,25(OH)(2)D(3) on
      inhibiting 1,25(OH)(2)D(3)-stimulated phosphate uptake in isolated enterocytes.
      Moreover, the molecular basis of such inhibition was suggested by the presence of
      two thioredoxin domains in the 1,25D(3)-MARRS protein/ERp57: Exposure of cells to
      either 24,25(OH)(2)D(3) or H(2)O(2) gradually reduced 1,25(OH)(2)D(3) binding to
      1,25D(3)-MARRS protein, between 10 and 20 min of incubation, but not to VDR.
      Feeding studies with diets enriched in the antioxidants vitamins C and E showed
      that net phosphate absorption in vivo nearly doubled relative to chicks on
      control diet. Antioxidant diets also resulted in increased [(3)H]1,25(OH)(2)D(3)
      binding to both 1,25D(3)-MARRS and VDR, suggesting benefits to both transcription
      and membrane-initiated signaling pathways. Intriguingly, phosphorous content of
      bones from birds on antioxidant diets was reduced, suggesting increased
      osteoclast activity. Because mature osteoclasts lack VDR, we analyzed a clonal
      osteoclast cell line by RT-PCR and found it contained the 1,25D(3)-MARRS mRNA.
      The combined data provide mechanistic details for the
      1,25(OH)(2)D(3)/24,25(OH)(2)D(3) endocrine system, and point to a role for the
      1,25D(3)-MARRS protein as a redox-sensitive mediator of osteoclast activity and
      potential therapeutic target.

PMID- 16817237
TI  - Calcium-pH crosstalks in the human mast cell line HMC-1: intracellular
      alkalinization activates calcium extrusion through the plasma membrane Ca2+
      ATPase.
AB  - The human mast cell line (HMC-1) has been used to study the relationship between
      intracellular pH and cytosolic calcium (Ca2+) in mast cells. Thapsigargin (TG)
      caused store-operated Ca2+ entry, that is enhanced by the PKC activator PMA.
      NH4Cl-induced alkalinization showed an inhibitory effect on TG-sensitive stores
      depletion (not on TG-insensitive stores), and also on final cytosolic Ca2+ levels
      reached in response to both TG and the ionophore ionomycin. Loperamide, a
      positive modulator of store-operated channels, induced a slight Ca2+ entry by
      itself, and also increased TG-induced Ca2+ entry. This enhancement was not enough
      to reverse the inhibitory effect of NH4Cl-induced alkalinization. When comparing
      the effect of NH4Cl-induced alkalinization on Ca2+ levels, with those observed
      using Ca2+ channel blockers (namely Ni2+ and SKF-96365), cytosolic profiles for
      this ion are different, either in modified saline solution or in HCO3(-)-free
      medium. Thus, it seems unlikely that the inhibitory effect of NH4Cl-induced
      alkalinization on Ca2+ is taking place by blockage of Ca2+ entry. Furthermore,
      inhibition of the plasma membrane Ca2+-ATPase (an important mechanism for Ca2+
      efflux) with sodium orthovanadate (SO) matches with the inhibition of the
      negative effect on Ca2+ levels elicited by NH4Cl. Data indicate that NH4Cl
      induced alkalinization might be activating Ca2+ efflux from the cell, by
      stimulation of the plasma membrane Ca2+-ATPase, and also confirm our previous
      finding that Ca2+ is a secondary signal to activate HMC-1 cells.

PMID- 16817238
TI  - Surface display of transglucosidase on Escherichia coli by using the ice
      nucleation protein of Xanthomonas campestris and its application in glucosylation
      of hydroquinone.
AB  - A surface anchoring motif using the ice nucleation protein (INP) of Xanthomonas
      campestris pv. campestris BCRC 12,846 for display of transglucosidase has been
      developed. The transglucosidase gene from Xanthomonas campestris pv. campestris
      BCRC 12,608 was fused to the truncated ina gene. This truncated INP consisting of
      N- and C-terminal domains (INPNC) was able to direct the expressed
      transglucosidase fusion protein to the cell surface of E. coli with apparent high
      enzymatic activity. The localization of the truncated INPNC-transglucosidase
      fusion protein was examined by Western blot analysis and immunofluorescence
      labeling, and by whole-cell enzyme activity in the glucosylation of hydroquinone.
      The glucosylation reaction was carried out at 40 degrees C for 1 h, which gave 23
      g/L of alpha-arbutin, and the molar conversion based on the amount of
      hydroquinone reached 83%. The use of whole-cells of the wild type strain resulted
      in an alpha-arbutin concentration of 4 g/L and a molar conversion of 16% only
      under the same conditions. The results suggested that E. coli displaying
      transglucosidase using truncated INPNC as an anchoring motif can be employed as a
      whole-cell biocatalyst in glucosylation.

PMID- 16817239
TI  - Eliminating non-renewable CO2 emissions from sewage treatment: an anaerobic
      migrating bed reactor pilot plant study.
AB  - The aim of this work was to demonstrate at pilot scale a high level of energy
      recovery from sewage utilising a primary Anaerobic Migrating Bed Reactor (AMBR)
      operating at ambient temperature to convert COD to methane. The focus is the
      reduction in non-renewable CO(2) emissions resulting from reduced energy
      requirements for sewage treatment. A pilot AMBR was operated on screened sewage
      over the period June 2003 to September 2004. The study was divided into two
      experimental phases. In Phase 1 the process operated at a feed rate of 10 L/h
      (HRT 50 h), SRT 63 days, average temperature 28 degrees C and mixing time
      fraction 0.05. In Phase 2 the operating parameters were 20 L/h, 26 days, 16
      degrees C and 0.025. Methane production was 66% of total sewage COD in Phase 1
      and 23% in Phase 2. Gas mixing of the reactor provided micro-aeration which
      suppressed sulphide production. Intermittent gas mixing at a useful power input
      of 6 W/m(3) provided satisfactory process performance in both phases. Energy
      consumption for mixing was about 1.5% of the energy conversion to methane in both
      operating phases. Comparative analysis with previously published data confirmed
      that methane supersaturation resulted in significant losses of methane in the
      effluent of anaerobic treatment systems. No cases have been reported where
      methane was considered to be supersaturated in the effluent. We have shown that
      methane supersaturation is likely to be significant and that methane losses in
      the effluent are likely to have been greater than previously predicted. Dissolved
      methane concentrations were measured at up to 2.2 times the saturation
      concentration relative to the mixing gas composition. However, this study has
      also demonstrated that despite methane supersaturation occurring, micro-aeration
      can result in significantly lower losses of methane in the effluent (<11% in this
      study), and has demonstrated that anaerobic sewage treatment can genuinely
      provide energy recovery. The goal of demonstrating a high level of energy
      recovery in an ambient anaerobic bioreactor was achieved. An AMBR operating at
      ambient temperature can achieve up to 70% conversion of sewage COD to methane,
      depending on SRT and temperature.

PMID- 16817240
TI  - The effects of methanol on the biofiltration of dimethyl sulfide in inorganic
      biofilters.
AB  - Air emissions from the pulp and paper industry frequently contain reduced sulfur
      compounds (RSC), such as dimethyl sulfide (DMS) mixed with volatile organic
      compounds (VOC) (e.g., methanol, MeOH) and it is desirable to treat either one or
      both of these groups of compounds. The objective of this study was to assess the
      effects of VOC (MeOH) on the biofiltration of DMS. Results obtained from
      continuous experiments using three bench-scale biofilters packed with inorganic
      material clearly show that MeOH has a positive effect (11-fold increase) on the
      biofiltration of DMS. Further experiments indicate that MeOH addition enhances
      biomass concentration and viability (threefold) in the biofilters. However, a
      suspension of MeOH addition causes a rapid significant increase (twofold) in the
      removal rate of DMS, suggesting that the presence of MeOH also has a competitive
      effect on DMS biodegradation. This negative effect was also confirmed in batch
      experiments. The decrease of biofilter performance with time for a long-term
      suspension of MeOH addition indicates that MeOH addition is necessary to sustain
      a high removal rate of DMS in inorganic biofilters. Results on metabolic products
      of DMS biodegradation demonstrate that DMS is almost completely converted to
      sulfate in the absence of MeOH, while it is partially oxidized to elemental
      sulfur in the presence of MeOH. This study suggests that there exists an optimum
      mix of DMS and MeOH for the treatment of DMS emissions in inorganic biofilters.

PMID- 16817241
TI  - Chemometrics and visible-near infrared spectroscopic monitoring of red wine
      fermentation in a pilot scale.
AB  - The modern wine industry needs tools for process control and quality assessment
      in order to better manage fermentation or bottling processes. During wine
      fermentation it is important to measure both substrate and product concentrations
      (e.g. sugars, phenolic compounds), however, the analysis of these compounds by
      traditional means requires sample preparation and in some cases several steps of
      purification are needed. The combination of visible/near-infrared (Vis/NIR)
      spectroscopy and chemometrics potentially provides an ideal solution to
      accurately and rapidly monitor physical or chemical changes in wine during
      processing without the need for chemical analysis. The aim of this study was to
      assess the possibility of combining spectral and multivariate techniques, such as
      principal component analysis (PCA), discriminant partial least squares (DPLS), or
      linear discriminant analysis (LDA), to monitor time-related changes that occur
      during red wine fermentation. Samples (n = 652) were collected at various times
      from several pilot scale fermentations with grapes from either Cabernet Sauvignon
      or Shiraz varieties, over three vintages (2001-2003) and scanned using a
      monochromator instrument (Foss-NIRSystems 6500, Silver Spring, MD) in
      transmission mode (400-2,500 nm). PCA was used to demonstrate consistent
      progressive spectral changes that occur through the time course of the
      fermentation. LDA using PCA scores showed that regardless of variety or vintage,
      samples belonging to a particular time point in fermentation could be correctly
      classified. This study demonstrates the potential of Vis/NIR spectroscopy
      combined with chemometrics, as a tool for the rapid monitoring of red wine
      fermentation.

PMID- 16817242
TI  - Binding capacity differences for antibodies and Fc-fusion proteins on protein A
      chromatographic materials.
AB  - A range of studies were carried out to investigate the underlying reason for
      differences in dynamic binding capacities observed with various antibodies and Fc
      fusion proteins during Protein A chromatography. Dynamic binding capacities were
      determined for these biomolecules using different protein A stationary phase
      materials. SEC was carried out to determine the relative sizes of the antibodies
      and fusion proteins. Pore diffusivities and static binding capacities were also
      determined on these Protein A resin materials. Trends in the dynamic binding
      capacities for these molecules did not correlate with differences in pore
      diffusion coefficients as might be expected for a mass transfer limited system.
      Instead, dynamic binding capacities were seen to follow the same trends as the
      static binding capacities and the apparent size of the molecules. Differences in
      static binding capacities were attributed to be due to differences in steric
      factor between the molecules. Solution binding stoichiometry studies were
      employed to estimate intra-Protein A steric effects while binding to the various
      domains within a Protein A ligand. In addition, steric hindrance was also found
      to exist between adjacent immobilized Protein A ligands on the chromatographic
      surface. The combination of intra and inter Protein A steric hindrances can
      explain differences in binding capacities observed between various antibody and
      Fc fusion proteins. The effect of Protein A ligand density on these supports was
      also examined and the results indicate that increasing Protein A ligand density
      leads to a situation of diminishing returns for binding capacity due to increased
      steric hindrance on the resin surface. The results presented in this paper show
      that steric hindrances can dominate over mass transfer effects in causing
      capacity variation between different molecules on the same stationary phase. This
      can lead to the development of more cost-efficient chromatographic stationary
      phases as well as provide information during the selection of Protein A media for
      preparative purification of monoclonal antibodies and Fc fusion proteins.

PMID- 16817243
TI  - Characterization of isoquinoline alkaloids, diterpenoids and steroids in the
      Chinese herb Jin-Guo-Lan (Tinospora sagittata and Tinospora capillipes) by high
      performance liquid chromatography/electrospray ionization with multistage mass
      spectrometry.
AB  - This study sought to determine the primary components (isoquinoline alkaloids,
      diterpenoids and steroids) in crude extracts of the Chinese herb Jin-Guo-Lan,
      prepared from the roots of Tinospora sagittata and T. capillipes, by liquid
      chromatography/electrospray ionization multistage mass spectrometry coupled with
      diode-array detection (LC-DAD/ESI-MS(n)). After separation on a reversed-phase
      C(18) column using gradient elution, positive and negative ESI-MS experiments
      were performed. In positive ion mode, the three types of compounds showed very
      different characteristic ions: strong [M](+) or [M+H](+) ions were observed for
      isoquinoline alkaloids; [M+NH(4)](+) and/or [M+H-CO(2)](+) for diterpenoids; [M+H
      nH(2)O](+) (n=1-3) for steroids. These adduct ions and/or fragments were used to
      deduce the mass and categories of known and unknown components in crude extracts,
      and their structures were further confirmed by ESI-MS(n) in positive ion mode.
      Moreover, UV absorption peaks obtained from DAD provided useful functional group
      information to aid the MS(n)-based identification. As a result, 11 compounds were
      unambiguously identified by comparing with standard compounds and 13 compounds
      were tentatively identified or deduced according to their MS(n) data. Two of
      these compounds (13-hydroxycolumbamine and 13-hydroxyjatrorrhizine) were found to
      be new compounds and another one (13-hydroxypalmatine) was detected for the first
      time as a natural product. In addition, a [M-*CH(3)-H(2)O](*+) ion in MS(2) of
      [M](+) after in-source collision-induced dissociation was used to differentiate
      positional isomers of protoberberine alkaloids, columbamine and jatrorrhizine.
      Although the roots of T. sagittata and T. capillipes contain almost identical
      compounds, the content of the compounds in them is dramatically different,
      suggesting the necessity for further comparison of the bioactivities of the two
      species.

PMID- 16817244
TI  - Electron ionisation and fast-atom bombardment mass spectrometry study of diaryl
      carbonates.
AB  - Electron ionisation mass spectrometry studies were performed previously for p
      diphenyl carbonate and some monosubstituted diphenyl carbonates. In this work, p
      diphenyl carbonate and p-methoxyphenylphenyl carbonate are re-examined, and p
      chlorophenyl phenyl carbonate and two disubstituted diphenyl carbonates, bis (p
      chlorophenyl) carbonate and p-methoxyphenyl-p-fluorophenyl carbonate, are studied
      for the first time. The previously established fragmentation routes were observed
      for all compounds investigated. Some other different sequences were observed, and
      a fragmentation path, other than decarboxylation, of the molecular ion is
      proposed. In the fast-atom bombardment study it was observed that the
      M(+*)/[MH](+) ion abundance ratio increased from 0.44 for compound 1 to 2.95 for
      compound 5. [MH](+) is not a dominant ion in most of compounds studied, in spite
      of the presence of a carbonyl group, a strong proton acceptor. The presence of
      two oxygen atoms bonded to the carbonyl group appears to induce delocalisation of
      the electron pairs, thus deactivating the carbonyl site for protonation. In
      addition, m-nitrobenzyl alcohol (NBA) being a relatively aprotic/hydrophobic
      matrix reinforces the deactivation for protonation. Because the carbonate group
      and NBA are common features to the study, the contributions of the substituents
      were taken into account to explain the different behaviour of the five compounds
      with respect to protonation.

PMID- 16817246
TI  - Bibliography. Current awareness in prenatal diagnosis.

PMID- 16817245
TI  - Accurate mass measurement using Fourier transform ion cyclotron resonance mass
      spectrometry for structure elucidation of designer drug analogs of tadalafil,
      vardenafil and sildenafil in herbal and pharmaceutical matrices.
AB  - Phosphodiesterase type 5 (PDE-5) inhibitors are a class of drugs used primarily
      in the treatment of erectile dysfunction. The Food and Drug Administration (FDA)
      approved PDE-5 inhibitors include sildenafil citrate, vardenafil hydrochloride
      and tadalafil. In this study, accurate mass measurements were made by
      electrospray ionization (ESI) using Fourier transform ion cyclotron resonance
      mass spectrometry (FTICRMS) to elucidate the structures of sildenafil, tadalafil
      and vardenafil analogs that were found in products marketed as dietary
      supplements. Initial detection of these analogs was accomplished through routine
      screening of suspect samples by liquid chromatography/electrospray ionization
      multi-stage mass spectrometry (LC/ESI-MS(n)) on a low-resolution ion trap
      instrument. The chromatographic behavior and mass spectrometric fragmentation
      patterns observed were often similar to those observed for FDA approved PDE-5
      inhibitors. The mass accuracy and resolving power associated with FTICRMS allows
      for the determination of elemental compositions. Elucidation of the product ion
      structures for the analogs was accomplished through the use of accurate mass
      measurements with the aid of Mass Frontier software (version 4.0). Using FTICRMS,
      accurate masses with measurement errors averaging <0.4 ppm were achieved,
      allowing assignment of one possible elemental formula to each fragment ion. The
      mass measurement errors associated with [M + H](+) for the analogs
      aminotadalafil, piperidino vardenafil, hydroxyacetildenafil and piperidino
      acetildenafil were 0.1, 0.0, 0.1 and 0.5 ppm, respectively. Based on the accuracy
      of the measurements, structural assignments could be made with a high degree of
      confidence.

PMID- 16817247
TI  - Chalk it down. By Caveman.

PMID- 16817248
TI  - Innovation in care and research: meeting highlights from the seventh Milan Breast
      Cancer Conference (Milan, 15-17 June, 2005).
AB  - The Seventh Milan Breast Cancer Conference (MBCC), Innovation in Care and
      Research, held in Milan, Italy from 15 to 17 June 2005 was attended by more of
      1100 physicians from 62 countries. This meeting report summarizes the highlights
      of the 12 sessions.

PMID- 16817249
TI  - [LDL target values in diabetic patients].

PMID- 16817250
TI  - Argument over HHABN implementation heats up between provider, patient advocacy
      groups.

PMID- 16817251
TI  - [Catheter removal in children--pain and anxiety free].

PMID- 16817253
TI  - [Aids for future planning for the urologist].

PMID- 16817252
TI  - [New occupational and public health insurance rights and 2006 future strategy for
      specialists].

PMID- 16817254
TI  - [Surgery of the female urethra: meatus-plasty, operation of the urethral
      caruncle, urethral prolapse and urethral diverticulum].

PMID- 16817255
TI  - Glucose concentration in 254 sudden infant death syndrome livers suggests
      pathophysiological heterogeneity.

PMID- 16817256
TI  - The deep inferior epigastric perforator flap for breast reconstruction, the
      learning curve explored.
AB  - The deep inferior epigastric perforator (DIEP) flap has been used as the
      principle tool for secondary breast reconstruction in our department. This
      article details our experience in learning and improving the technique with the
      help of an external team of experienced surgeons. In our initial 65 DIEP flap
      breast reconstructions our total flap loss rate was reduced from 9.5 to 0%,
      partial flap loss rate from 31 to 0%, and fat necrosis rate from 17 to 4.3%. We
      illustrate how a surgical team, which might initially have considered the
      complication rate from DIEP flap breast reconstruction too high, can benefit from
      a staged approach to this complex, but useful, reconstruction technique.

PMID- 16817257
TI  - Breast reconstruction using deep inferior epigastric perforator flaps in EEC
      syndrome.
AB  - Ectrodactyly, ectodermal dysplasia, cleft lip/palate (EEC) syndrome is a rare
      condition that may result in failure of breast development. Breast reconstruction
      in these patients may pose a challenging problem, as they are young and
      reconstructive options should have minimal long-term complications. The use of
      deep inferior epigastric perforator (DIEP) flaps in breast reconstruction
      following breast cancer has been well described with good results. The use of
      DIEP flaps in breast augmentation, however, is far less common. We present the
      case of a young patient with EEC syndrome and mammary hypoplasia who underwent
      DIEP flap reconstruction for breast augmentation. The outcome was satisfactory to
      both patient and surgeon.

PMID- 16817258
TI  - More degrees of freedom by using chimeric concept in the applications of
      anterolateral thigh flap.
AB  - For obliterating a dead space, especially deep and slender, it is more
      challenging for a reconstructive surgeon to design a musculocutaneous flap by
      conventional technique. Tethering at the midway of a musculocutaneous flap while
      inset is not unusual, and trimming of excess muscle may jeopardize the perfusion
      of the skin. Based on the lateral femoral circumflex system (LFCS), introducing a
      chimeric concept into the reconstruction of these difficult wounds will simplify
      the flap design and give more degrees of freedom to inset the flap. Technique of
      intramuscular dissection of perforators is frequently demanded. Vastus lateralis
      muscle based on the distal runoff of the LFCS can be included with sharp
      dissection. Using chimeric concept in the application of anterolateral thigh
      flap, the muscle and skin can be considered as individual units although they
      base on a single pedicle. The dimension of skin and the volume of muscle can be
      tailored as adequate as desired. While insetting the flap, the lengthy pedicles
      distal to the bifurcation enhance a three-dimensional reconstruction without
      difficulty. Chimeric concept of anterolateral thigh flap affords more degrees of
      freedom for difficult reconstructions.

PMID- 16817259
TI  - Anterolateral thigh perforator flap from previously burned skin for secondary
      reconstruction of neck with post burn sequelae, new limits explored.
AB  - We report the use of anterolateral thigh perforator flap (ALTF) from previously
      burned skin for reconstruction of burn cervical contracture. At the time of
      treatment, there are no reports of the use of perforator flaps from previously
      burned skin. We have used this technique and feel that it might be an option to
      consider in view of the fact that massively burned patients often have limited
      donor site availability, despite requiring flap tissue to resurface difficult
      anatomical regions.

PMID- 16817260
TI  - Haemodynamic enhancement in perforator flaps: the inversion phenomenon and its
      clinical significance. A study of the relation of blood velocity and flow between
      pedicle and perforator vessels in perforator flaps.
AB  - Perforator flaps are perfused through a long vessel whose calibre decreases from
      its origin to the skin, because all branches have been sealed, resulting in a
      conduit with resistances in series, rather than a tree with resistances in
      parallel, as in the normal systemic circulation. This study was planned to assess
      whether the differences between perforator flap and normal systemic vasculature
      have an impact on haemodynamic parameters in perforator flaps and on their
      clinical significance. The study was performed on 10 patients. Echo-colour
      Doppler measurement of diameters, velocity of flow and calculations of flow rate
      were made at the level of flap pedicle artery and skin perforator artery, pre-
      and post-operatively in each patient. Statistical analysis used the Wilcoxon
      matched pairs signed sum rank test. Our data show that in the donor area pre
      operatively, blood velocity in skin artery perforator is lower that in the
      corresponding pedicle artery, whereas post-operatively, in perforator flaps,
      blood velocity in the perforator is higher than in the pedicle. The difference
      was statistically significant (P<0.01). There is an inversion of the gradient of
      blood velocity between pedicle artery and perforator artery compared to normal
      circulation. Furthermore, in normal circulation flow through the perforator was
      found smaller than that at the pedicle, whereas in perforator flaps, flow through
      the perforator is smaller but is a greater proportion of the flow through the
      pedicle and the difference is statistically significant (P<0.01). Therefore, the
      velocity of blood and the rate of flow reaching the skin are higher in perforator
      flaps than in normal circulation.

PMID- 16817262
TI  - Deep inferior epigastric perforator flap (DIEP) breast reconstruction in the
      presence of a midline vertical scar.

PMID- 16817261
TI  - A systematic multiple stage surgical approach for attainment of satisfactory and
      favourable surgical results in an extremely severe von Recklinghausen's disease,
      elephantiasis neurofibromatosa.
AB  - This disease was first described by von Recklinghausen and Festscher and has been
      known as the von Recklinghausen's disease or neurofibromatosis (NF). Numerous
      articles have been published on this subject where majority of the authors have
      stressed their difficulty in achieving favourable surgical results. This disease
      is pathologically accepted to be of neuroectodermal origin with a positive family
      history in approximately 50% of the cases, autosomal dominant trait and is known
      to involve the periorbital regions, orbit (preoperative CT scan: upper left and
      right photographs), temporal region to a variable extent, mid-facial region to
      the mandibular region. The indicated treatment for this disease is surgery
      including cranio-maxillofacial surgery even though re-evaluation of the
      conventional methods of surgery should be considered. This particular case is an
      extremely difficult and challenging case for any reconstructive plastic surgeon
      and required extensive preoperative planning. The systematic multiple stage
      surgical approach for an extremely severe von Recklinghausen's disease,
      elephantiasis neurofibromatosa is presented and discussed in detail.

PMID- 16817264
TI  - An observation on the acupuncture treatment of ischemic wind-stroke with
      different lengths of needle-retaining time.
AB  - OBJECTIVE: To observe the effects of different lengths of needle-retaining time
      on the therapeutic results of acupuncture treatment for ischemic wind-stroke.
      METHODS: According to the severity of disease, 251 cases of ischemic wind-stroke
      were randomly divided into 3 groups and treated by acupuncture, with the needle
      retaining time lasting 20, 40, and 60 minutes respectively. Observation was
      mainly focused on the scores of nervous dysfunction and the clinical therapeutic
      results. RESULTS: The comparison of the scores of nervous dysfunction in the 3
      groups before and after the treatment showed that under Wilcoxon's pair-match
      symbol rank test, except for horizontal gaze, other indexes all showed
      significant differences (P < 0.01). In the between-group comparison before and
      after the treatment, there showed significant or very significant differences in
      the indexes of myodynamia of the upper limb, myodynamia of hand and the total
      scores (P < 0.05, P < 0.01). In the between-group comparison by Mann-Whitney rank
      test of the indexes of myodynamia of upper limb, myodynamia of hand and the total
      scores, the 20-min. group and the 60-min. group showed significant differences (P
      < 0.05); and 40-min. group and 60-min. group showed significant differences in
      myodynamia of upper limb (P < 0.05). In comparison of the therapeutic effects of
      the 3 groups by Kruskal-wallis rank test, there showed very significant
      differences (P < 0.01). In the between-group comparison by Mann-Whitney rank
      test, the 40-min.group and 60-min. group showed significant differences (P =
      0.013); while the 20-min. group and 60-min. group showed very significant
      differences (P = 0.000). CONCLUSION: There is a time-effect relationship between
      the length of needle-retaining time and the therapeutic effects of acupuncture
      for ischemic wind-stroke.

PMID- 16817265
TI  - Effect of "phased whole acupuncture therapy" on ability of daily life in 63 cases
      of cerebral infarction-induced hemiplegia.
AB  - OBJECTIVE: To observe the effect of "phased whole acupuncture therapy" on the
      ability of daily life (ADL) of the patients with cerebral infarction-induced
      hemiplegia. METHODS: 113 patients were randomly divided into a treatment group
      (n=63) treated with phased whole acupuncture and a control group (n=50) treated
      with traditional acupuncture. After the treatment, the improvement of ADL was
      compared between the two groups. RESULTS: Patients in the treatment group
      obtained satisfactory therapeutic effects in ADL improvement and in lowering of
      deformed rate, which were superior to those in the control group. CONCLUSION: The
      phased whole acupuncture is an effective therapy in treating cerebral infarction
      induced hemiplegia, which can better improve the life quality of the patients.

PMID- 16817266
TI  - Effects of CT-localized scalp round-needling on the blood rheology, NO and NOS of
      patients with multiple infarctional dementia.
AB  - OBJECTIVE: To observe the short-term therapeutic effects of CT-localized scalp
      round-needling on the blood rheology, nitric oxide (NO) and nitric oxide
      synthetase (NOS) of patients with multiple infarctional dementia. METHODS: 89
      cases of multiple infarctional dementia were randomly divided into an electro
      round-needling group (57 cases), and a western medication group (32 cases). The
      therapeutic effects, including the effects on the blood rheology, NO and NOS,
      were observed. RESULTS: After receiving same courses of treatment, both the
      electro-round-needling group and the western medication group showed significant
      differences in the various kinds of indexes (P < 0.05-0.01). CONCLUSION: The CT
      localized scalp round-needling is an effective therapy for multiple infarctional
      dementia.

PMID- 16817267
TI  - Clinical application of the acupuncture manipulation methods of warm-reinforcing
      and cool-reducing.

PMID- 16817268
TI  - Location of Yaotong point and the optimal time of its needling.
AB  - OBJECTIVE: To determine the location of Yaotong point and the optimal time of its
      needling in the treatment of acute lumbar sprain. METHOD: Thirty-five cases of
      acute lumbar sprain were retrospectively analyzed for the location of Yaotong
      point and the method of its needling according to their disease courses and
      effects. RESULTS: The optimal time of needling is 1-3 days after lumbar sprain,
      and the location of Yaotong points on both hands correspond to the location of
      sprain. CONCLUSION: This correspondence is useful in

PMID- 16817269
TI  - Thirty cases of sub-healthy state regulated by acupuncture and He-Ne laser
      vascular irradiation.

PMID- 16817270
TI  - Role of Du Channel in treating senile dementia.

PMID- 16817271
TI  - Acupuncture treatment of children nocturnal enuresis--a report of 56 cases.
AB  - OBJECTIVE: To observe the effect of acupuncture in treating nocturnal enuresis in
      children. METHOD: Shenmen (HT 7) and Weizhong (BL 40) are selected as the main
      points. Zhongji (CV 3) and Shenshu (BL 23) are added for warming and
      supplementing the lower origin, and Qihai (CV 6) and Taiyuan (LU 9) for
      supplementing the middle-jiao and reinforcing the qi, Taichong (LR 3) and
      Xingjian (LR 2) for clearing away the damp-heat. RESULTS: 56 cases were treated
      with a total effective rate of 96%. CONCLUSION: Nocturnal enuresis is a condition
      due to imbalance between the Heart Channel and Bladder Channel. Shenmen (HT 7), a
      point pertaining to the Heart Channel of Hand-Shaoyin and Weizhong (BL 40), a
      point pertaining to the Bladder Channel of Foot-Taiyang are selected as the main
      points, with a good result.

PMID- 16817272
TI  - Examples for application of hegu (LI 4).

PMID- 16817273
TI  - Essentials for acupuncture treatment of periarthritis of shoulder.

PMID- 16817274
TI  - Clinical observation on senile patients with impaired glucose tolerance treated
      by point application.
AB  - In order to observe and evaluate the therapeutic effects of point application on
      senile impaired glucose tolerance (IGT), 64 senile IGT patients were randomly
      divided into two groups with 32 cases in each group. The control group was
      treated with interference therapy of controlling diet, while the observation
      group was given point application at Yishu ([Chinese characters: see text] 1.5
      cun lateral to the Du Channel, at the level of the lower border of the spinous
      process of the eighth thoracic vertebra), Pishu (BL 20), Sanyinjiao (SP 6),
      Zusanli (ST 36) and other points in addition to interference therapy of
      controlling diet. After 2 courses of treatment, the postprandial blood sugar was
      detected. As a result, the postprandial blood sugar obviously reduced in both
      groups (P < 0.05, P < 0.01) with a lower level in the observation group than in
      the control group (P < 0.05), indicating that point application in combination
      with interference therapy of controlling diet has a reliable therapeutic effect
      on senile IGT patients.

PMID- 16817275
TI  - Treatment of Meniere's disease with a heavy dosage of gu sui bu (Rhizoma
      Drynariae).

PMID- 16817276
TI  - Study on atherosclerosis treated with theory of detoxification.
AB  - Starting with the contents, classification and pathogenic characteristics of the
      toxic pathogen and combining the modern medical research on the correlation of
      atherosclerosis with inflammation and immune reaction, authors have studied and
      expounded the interrelationship between the toxic pathogen and atherosclerosis.
      The toxic pathogen affecting the whole pathological process of atherosclerosis is
      a key factor for the disease to remain lingering and a cause of various
      cardiocerebrovascular diseases. Detoxification can be used to treat
      atherosclerosis so as to enhance the toxin-removing ability of the body and
      resist the damage to the body from the toxic pathogen.

PMID- 16817278
TI  - Treatment of tension headache with Chinese herbs and acupuncture--a report of 40
      cases.

PMID- 16817277
TI  - Effects of replenishing qi, promoting blood circulation and resolving phlegm on
      vascular endothelial function and blood coagulation system in senile patients
      with hyperlipemia.
AB  - OBJECTIVE: To observe the curative effect of the method of replenishing qi,
      promoting blood circulation and resolving phlegm on senile hyperlipemia and its
      effects on vascular endothelial function and blood coagulation system. METHOD: 96
      patients with senile hyperlipemia were randomly divided into a treatment group
      and a control group. 56 patients in the treatment group orally took danshen
      jueming granules while 40 patients in the control group orally took xuezhikang
      capsules. Observed were indexes of blood lipid, vascular endothelial function,
      blood coagulation system and safety. RESULTS: After treatment, the treatment
      group was obviously superior to the control group (P < 0.05) in reducing plasma
      total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as well as
      in the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1alpha (6-keto
      PGF1alpha), D-dimer (D-D) and fibrinogen (FIB). CONCLUSION: Danshen Jueming
      Granules have the effect of regulating metabolism of blood lipid, and improving
      vascular endothelial function and blood coagulation system in senile patients
      with hyperlipemia.

PMID- 16817279
TI  - Treatment of reflux laryngopharyngitis with modified banxia xiexin tang (Pinellia
      decoction for draining the heart)--a report of 40 cases.
AB  - OBJECTIVE: To evaluate the effect of modified banxia xiexin tang ([Chinese
      characters: see text] Pinellia Decoction for Draining the Heart) in treatment of
      laryngopharyngitis caused by gastroesophageal reflux disease (GERD). METHODS:
      Forty patients in the treatment group were treated with modified Pinellia
      Decoction for Draining the Heart and 38 patients in the control group were
      treated with Jinsang Liyan Wan ([Chinese characters: see text] Pills for a Good
      Voice by Relieving Sore-Throat). The effects were evaluated by the improvement in
      symptoms and the parameters obtained in a grading system of gastroscopy and
      laryngoscopy. RESULTS AND CONCLUSION: The comparison of therapeutic effects on
      complication of laryngopharyngitis, GERD symptoms, and findings in gastroscope
      grading and laryngoscope (P < 0.05 or P < 0.01) demonstrated that the modified
      Pinellia Decoction for Draining the Heart was much more effective in treating
      laryngopahryngitis caused by gastroesophageal reflux.

PMID- 16817280
TI  - A study of Dr. Gao Huiyuan's new prescriptions.

PMID- 16817281
TI  - Acupuncture increases bone strength by improving mass and structure in
      established osteoporosis after ovariectomy in rats.
AB  - The effects of acupuncture on bone biomechanical properties and histomorphometry
      in ovariectomized (OVX) rats were studied. Twenty-four 8-week-old female Sprague
      Dawley rats were randomly assigned to three groups: sham, model and acupuncture.
      Rats in the model and acupuncture groups were ovariectomized, while those in the
      sham group underwent a sham operation. All rats were anesthetized and fastened
      for 15 minutes, and for the acupuncture group, needling on Pishu (BL20) and
      Shenshu (BL23) was performed. Blood and urine were collected to measure serum
      osteocalcin (OC) and urinary calcium, phosphorus or deoxypyridinoline (Dpd).
      After 16 weeks of treatment, all the rats were killed and their tibiae and femora
      were removed. The tibiae were used for analyses of bone histomorphometry and the
      femora for a three-point bending test. Acupuncture gave significant protection
      against ovariectomy-caused decline on femoral strength in the mechanical test,
      increased the trabecular bone volume and thickness, lowered the trabecular
      separation of tibiae and restricted the excretion of phosphorus and Dpd, while
      promoting the concentrations of serum osteocalcin as compared with model rats.
      These results seemed to indicate that acupuncture on the points of Pishu (BL20)
      and Shenshu (BL23) not only promoted the bone formation but also suppressed the
      bone resorption induced by OVX in osteoporotic rats, which suggests that it would
      be a potentially useful and convenient method in preventing osteoporosis.

PMID- 16817282
TI  - Effect of electroacupuncture at acupoints of the governor vessel on aquaporin-4
      in rat with experimental spinal cord injury.
AB  - This study is to investigate the effects of electroacupuncture at acupoints of
      the Governor Vessel (GV) on aquaporin-4 (AQP-4) expression and on functions of
      the hind limbs in the rat of spinal cord injury. The functions of the hind limbs
      were detected with BBB scale on the 1d, 3d, 7 d and 21 d after the spinal cord
      injury, respectively, and AQP-4 expression in the spinal cord was determined with
      immunohistochemical method and analyzed quantitatively with image analyzer. The
      results indicated that on the 1 d after the spinal cord injury, increased AQP-4
      expression can be seen significantly in both the gray matter and the white matter
      of the injured spinal cord, and it reached the peaks on the 3d after the spinal
      cord injury in both the electroacupuncture group and the spinal cord injury
      group. However, AQP-4 express was significantly decreased in the
      electroacupuncture group as compared with that in the control group on 7 d, 14 d
      and 21 d (P < 0.05 or P < 0.01). The decrease of AQP-4 expression almost went
      with the improvement of the neurological function, which suggested that
      electroacupuncture at the acupoints of the Governor Vessel can inhibit edema of
      the spinal cord to alleviate the secondary spinal cord injury by means of
      decreasing the AQP-4 expression after the spinal cord injury, so as to protect
      the residual normal spinal cord tissues and promote the rebuilding of nervous
      tissues.

PMID- 16817283
TI  - Effects of buyang huanwu decoction on apoptosis of nervous cells and expressions
      of Bcl-2 and bax in the spinal cord of ischemia-reperfusion injury in rabbits.
AB  - OBJECTIVE: To study the effect of buyang huanwu decoction ([Chinese characters:
      see text] BYHWD) on spinal ischemia-reperfusion injury and explore the possible
      mechanism involved. METHOD: 27 model rabbits with ischemia-reperfusion injury
      were randomly divided into a sham operation group, a model group and a BYHWD-pre
      treated group. 24 and 48 hours after the ischemia-reperfusion injury, the motor
      functions of hind limbs were observed, the expressions of apoptosis-related
      proteins bcl-2 and Bax in the spinal tissue were investigated with the
      immunohistochemical methods and apoptosis of nervous cells with TUNEL straining;
      and the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in
      the spinal cord were then determined. RESULTS: BYHWD can improve significantly
      the motor function of hind limbs, increase SOD activity and decrease the level of
      MDA, up-regulate expression of Bcl-2 and down-regulated expression of Bax, and
      depress apoptosis of nervous cells in the spinal cord caused by the ischemia
      reperfusion in the rabbits. CONCLUSION: BYHWD has a protective action on the
      spinal ischemia-reperfusion injury, and the mechanisms may be related to the
      decrease of lipid peroxidation and inhibition of apoptosis of nervous cells.

PMID- 16817284
TI  - A survey of TCM studies on systemic scleroderma.

PMID- 16817285
TI  - Direct evidence of endothelial injury during cardiopulmonary bypass by
      demonstration of circulating endothelial cells.
AB  - Endothelial activation is considered a key process in the development of a whole
      body inflammatory response secondary to cardiopulmonary bypass (CPB). Increased
      levels of a multitude of soluble mediators have been described as being released
      during and after cardiac surgery. Circulating endothelial cells have recently
      been established as a novel marker of endothelial damage in a variety of vascular
      disorders. Blood samples from 20 patients undergoing elective coronary artery
      bypass surgery were obtained preoperatively and 1, 6, 12, 24, and 48 h after
      termination of CPB. Control samples were obtained from ten healthy volunteers.
      Circulating endothelial cells (CEC) were isolated with immunomagnetic anti-CD146
      coated Dynabeads, and counted in a Nageotte chamber. Low numbers of CEC were
      observed in healthy control volunteers (12 +/- 6 cells/mL; median: 9 cells/mL).
      CEC numbers were already significantly elevated in all patients before CPB, and
      there was a further significant increase after weaning from CPB (maximum increase
      at 6 h after CPB: 73 +/- 30 cells/mL; range: 30-153 cells/mL, p < 0.001). The
      number of CEC provides further and direct evidence that CPB is associated with a
      pronounced endothelial injury and/or damage. CEC appear to be most useful markers
      for vascular endothelial activation because they are specific, stable, and
      circulating components of injured vessel wall.

PMID- 16817286
TI  - Is body surface area still the best way to determine pump flow rate during
      cardiopulmonary bypass?
AB  - For over four decades, pump flow rate during cardiopulmonary bypass (CPB) has
      been estimated using body surface area (BSA). As patients presenting for heart
      surgery are increasingly obese, this approach may no longer be appropriate and
      other estimates of systemic metabolism should be used, such as body mass index
      and lean body mass. Mixed venous oxygen saturation (SvO2) is a robust and
      independent estimate of the global efficacy of CPB. The aim of this study was to
      determine which factors, including body surface area, body mass index and lean
      body mass, best predict SvO2 during CPB. Forty-eight patients undergoing elective
      cardiac surgery requiring CPB were studied. Patients' height, weight and skinfold
      thickness at four sites (biceps, triceps, subscapularis and suprailiac) were
      measured. Body surface area, lean body mass and body mass index were then
      calculated. Pump flow rate was maintained at 2.4 L/min/ m2 during CPB as per
      standard unit protocol. Arterial and mixed venous blood samples were taken during
      the cooling, stable hypothermia and rewarming phases of CPB. Nasopharyngeal
      temperatures and flow rates were recorded contemporaneously. The blood samples
      were analysed for oxygen saturation, haemoglobin concentration and partial
      pressures of oxygen and carbon dioxide. The values of the three time points were
      meaned. All potential predictor variables were then univariately correlated with
      mixed venous oxygen saturation (SvO2). Those correlating significantly (p < 0.1)
      were entered into a multivariate linear regression model. Nasopharyngeal
      temperature (beta = 0.615, p < 0.001) and lean body mass (beta = 0.256, p <
      0.028) were the only significant predictors of SvO2 (r2 = 0.433, p2 < 0.001).
      Pump flow rates maintained at 2.4 L/min/m2 throughout CPB results in relative
      over-perfusion during hypothermia. Lean body mass may be a more sensitive
      estimate of systemic metabolism and, therefore, may provide a more accurate means
      of determining pump flow rate than body surface area in patients undergoing heart
      surgery.

PMID- 16817287
TI  - Influence of hematocrit and pump prime on cerebral oxygen saturation in on-pump
      coronary revascularization.
AB  - BACKGROUND: The couplings between cerebral oxygenation (rSO2), on-pump hematocrit
      and circuit prime are explored in this study. METHODS: Thirty-eight consecutive
      patients undergoing coronary revascularization with cardiopulmonary bypass (CPB)
      were matched on preoperative hematocrit < 40% and > 40% (n = 16). Similarly, six
      blood prime patients were matched with six crystalloid prime patients. Hematocrit
      and rSO2 levels were then compared on CPB. RESULTS: The preoperative hematocrit >
      40% group retained higher levels on pump run (p < 0.01) and significantly higher
      rSO2 prior to CPB (64.8 +/- 9.6 versus 73.2 +/- 7.3), and on and off CPB (61.1 +/
      8.8 versus 67.4 +/- 6.4). Blood priming increased absolute rSO2 (2.3 +/- 6.3
      versus -10.9 +/- 5.9) and % rSO2 (4.7 +/- 11.8 versus -14.2 +/- 7.4%) in the low
      hematocrit group. CONCLUSION: Blood primes are instrumental in high-risk and low
      preoperative hematocrit patients in preventing cerebral oxygen desaturation
      during initiation and maintenance of CPB.

PMID- 16817288
TI  - Changes in muscle compartment pressure after cardiopulmonary bypass.
AB  - PURPOSE: Hemodilution and inflammation lead to edema and increased muscle
      compartment pressure after cardiac surgery. The aim of this study was to find
      whether muscle compartment pressure was affected by the addition of albumin and
      mannitol to the pump prime, heparin coating or leukocyte depletion. Additionally,
      we studied the relationship between intraocular pressure and lower leg muscle
      compartment pressure. Edema during and following cardiac surgery is due to
      hemodynamic, osmotic and inflammatory changes, according to Starling's Law. We
      attempted to influence the osmotic balance and reduce the inflammatory response
      in order to reduce the edema. METHODS: Thirty-six patients who underwent cardiac
      surgery were randomly allocated into four groups. Group A received albumin and
      mannitol into the pump prime. Group B had an, heparin-coated perfusion system,
      Group C had a leukocyte-depletion arterial line filter and Group D was the
      control group, where intraocular pressure was also measured. RESULTS: Lower leg
      muscle compartment pressure increased significantly during and after cardiac
      surgery in all groups, but this increase was significantly less in Group A than
      in the control group 24 h after surgery. No correlation was found between
      muscular compartment pressure and intraocular pressure. The intraocular pressure
      profile is different from the muscular compartment pressure and recovers much
      faster. CONCLUSION: Lower leg muscle compartment pressure and intraocular
      pressure behave differently during and after cardiac surgery. Albumin and
      mannitol added to the pump prime decreases muscle compartment pressure after
      cardiac surgery.

PMID- 16817289
TI  - Adhesion of thrombotic components to the surface of a clinically used oxygenator
      is not affected by Trillium coating.
AB  - The Trillium coating is designed to minimize adsorption of protein and the
      attachment of cells and other particles. The present study was undertaken to
      investigate the effect of surface coating on the adhesion of thrombotic
      components (activated platelets, white blood cells and fibrin) to the surface of
      a clinically used oxygenator. Twenty patients undergoing elective coronary artery
      bypass grafting (CABG) were randomized to one of the two oxygenator groups: non
      coated (NC, n = 10) or Trillium-coated (TC, n = 10). Platelet and white blood
      cell counts and factor XIIa concentrations were determined prior to the induction
      of anesthesia and at the end of cardiopulmonary bypass (CPB). Binding of
      activated platelets, white blood cells and fibrin to the artificial surfaces was
      quantified by means of antibody binding and histological validation was achieved
      by scanning electron microscopy. Patient demographic and CPB data were similar
      for the two groups. No significant differences between the groups were found for
      any of the tested thrombotic components. However, observations from our scanning
      electron microscopy suggested a release of formed particles from the Trillium
      coated surface. Primary adhesion of activated platelets, white blood cells and
      fibrin to the artificial surface of the venous blood inlet from an oxygenator is
      not affected by the Trillium surface coating under conditions of full systemic
      heparinization.

PMID- 16817290
TI  - Hyperkalemia of the blood-primed ECLS circuit does not result in post-initiation
      hyperkalemia in infants < 10 kg.
AB  - OBJECTIVE: To assess the risk of hyperkalemia with blood-primed extracorporeal
      life support (ECLS) circuits in infants < 10 kg. DESIGN: Retrospective cohort
      study of all neonatal and pediatric patients < 10 kg placed on ECLS from May 1998
      to April 2001. MEASUREMENTS AND MAIN RESULTS: Data collection including patient
      weight, patient potassium levels pre- and post-initiation of ECLS, potassium
      level of the primed ECLS circuit, age of the packed red blood cell (PRBC) unit,
      type of preservative, and preservative reduction status. Seventy-six circuits
      were available for the analysis. The age of the PRBC unit and preservative
      reduction status significantly affected the potassium level of the primed ECLS
      circuit. Multivariate linear regression analysis showed no significant effect on
      the post-ECLS initiation patient potassium level with respect to the PRBC age,
      the preservative reduction status, the patient potassium level prior to ECLS
      initiation, and the potassium level of the primed ECLS circuit. CONCLUSIONS:
      Initiation of ECLS in infants < 10 kg should not be delayed unnecessarily to
      perform preservative reduction or to utilize PRBC units of a specific age, as
      hyperkalemia of the primed ECLS circuit is not associated with systemic
      hyperkalemia in the patient post-initiation of ECLS.

PMID- 16817291
TI  - Myocardial protective effects of nicorandil, an opener of potassium channels on
      senile rat heart.
AB  - The purpose of this study was to investigate the cardioprotective effects of
      nicorandil, an opener of potassium channels, on senile rat hearts from ischemic
      reperfusion injury. A modified working model of isolated perfused hearts of
      senile rats was used. After isolation, the hearts underwent 60 min of global
      hypothermic ischemia treatment, followed by 30 min of reperfusion. These hearts
      were distributed into three groups, each receiving different cardioplegic
      solutions: (1) St. Thomas' solution (Group S), (2) 100 micromol/L nicorandil
      (Group N), (3) St. Thomas' solution combined with 100 micromol/L nicorandil
      (Group S+N). The pre- and post-ischemic myocardial function were assessed by the
      percentage recovery of the heart rate (HR), +/- dp/dt(max) (maximal rate of
      change of left ventricular pressure) and cardiac output (CO). Upon reperfusion,
      the cardioplegic solution was collected from the coronary sinus and tested for
      lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity. During 30
      min of reperfusion, the percentage recovery of HR, +dp/dt and left ventricular
      stroke work (LVSW) were significantly higher in Group S+N than in Group S and
      Group N (p < 0.05). The percentage of recovery in CO was higher in Group N and
      Group S+N than in Group S. The electrical activities arresting time (EAT) and
      mechanical activities arresting time (MAT) were longer in Group N than in Group S
      and Group N+S (p < 0.01). There were no statistical significance between Group S
      and Group N+S (p > 0.05). There were no significant differences in the levels of
      LDH and CK-MB. Electron microscopic examination revealed better preservation of
      the ultrastructures of the myocardial tissue in Group N+S than the other two
      groups. These results indicate that nicorandil combined with St. Thomas' solution
      can improve the left ventricular function of the post-ischemic senile rat and
      offer a better myocardial protective effect on the ischemic senile myocardium.

PMID- 16817292
TI  - Cardiopulmonary bypass in the immature fetus through novel use of a mini
      centrifugal pump.
AB  - The concept that the natural history of certain heart defects could be positively
      modified through in utero intervention has stimulated extensive research in fetal
      cardiac intervention and surgery since the early 1980s. Since the management of
      certain defects would require the use of cardiopulmonary support, extensive
      studies have been directed toward the application of a variety of perfusion
      circuits. The unique features of the fetal patient have directed the focus of
      many of these designs toward miniaturization of components and minimization of
      prime volume. Large extracorporeal surface contact areas and prime volumes have
      been identified as potential contributors to a frequently observed placental
      dysfunction following fetal cardiopulmonary bypass (CPB). We set out to develop
      means of CPB using a centrifugal micro-system that would not require supplemental
      prime volume. We describe the unique application of an adult right heart assist
      device, primarily used for 'off-pump' coronary revascularization for fetal
      cardiopulmonary support. Finally, while previous fetal experiments have used late
      gestation mature fetuses, we studied more immature fetuses of mid-gestation,
      relevant to current clinical attempts in fetal therapy.

PMID- 16817293
TI  - The nurse's responsibility in creating a 'nurse-friendly' culture in the
      workplace.

PMID- 16817294
TI  - Getting to the heart of the NPSGs.

PMID- 16817295
TI  - Nursing care of the person having bariatric surgery.
AB  - The increasing incidence of morbid obesity suggests that the quantity of
      bariatric surgical procedures will continue to multiply each year. Bariatric
      surgery has become an accepted approach to weight management with the additional
      benefit of resolution of several co-morbidities. However, quality nursing care
      and effective patient teaching are essential to achieve positive patient
      outcomes. Nursing care along the continuum of the bariatric surgical experience
      is key to positive outcomes for these patients. Throughout the process from
      selection for surgery to follow-up visits in the physician's office, the nurse
      can have a significant impact on the response of the patient and family to the
      surgical procedure. During the selection process, the nurse can explain the
      required diagnostic tests and their rationale and conduct a thorough medical
      history, informing the physician of pertinent information that might affect the
      patient's outcomes. Patient and family teaching begins at this stage with
      information about the peri-operative experience. Bariatric surgery results in a
      major lifestyle change for the patient. This change will evolve over time as
      weight is lost, and the patient adjusts to changes in eating patterns, body
      image, and the perceptions of others. The nurse should see that the patient has
      appropriate referral information for support services and should follow up to see
      that the patient and family availed themselves of these services. The patient's
      stay in acute care is usually very short. Clearly the patient and family need to
      go home with specific information about drinking/eating, caring for drainage
      tubes, skin and wound care, ambulation, self-care, and signs and symptoms that
      require medical attention. Nursing care should include written information and
      demonstrations of such activities as care of the wounds and drains. The nurse
      should assure that the patient leaves the hospital with a call number if
      questions arise at home. Ideally the nurse, patient, and family should have an
      opportunity for private education sessions prior to discharge. During the
      postoperative period, the nurse in the physician's office can serve as a source
      of information and a monitor of patient progress. Follow-up calls to patients and
      families after surgery are very helpful in determining the welfare of the
      patient, offering suggestions for managing the patient's care, and learning if
      any complications are developing. At the same time, the nurse can assess the
      psychological condition of the patient and his or her adjustment to a new way of
      living.

PMID- 16817296
TI  - Collaborating with chaplains to meet spiritual needs.
AB  - Current accreditation and professional standards in health care reflect the
      importance of chaplaincy services to patients, families, the health care team,
      and the organization. However, inadequate spiritual assessment, the
      organizational structure and climate, and lack of understanding of the chaplain's
      role can prevent these services from being optimally utilized. Chaplains are
      trained extensively to provide spiritual care to patients, families, and staff as
      they assist in meeting the organization's mission to provide patient-centered
      care. Spiritual assessment is a tool for nurses to recognize patient's needs for
      spiritual intervention and chaplain referral. By collaborating with chaplains,
      nurses can help develop an organizational infrastructure capable of timely
      responsiveness to patients' spiritual needs.

PMID- 16817297
TI  - Team approach demonstrates success in intermediate respiratory unit.

PMID- 16817298
TI  - Physical restraint use: a nursing perspective.

PMID- 16817299
TI  - Lung cancer epidemiology.

PMID- 16817300
TI  - Improving care of the older adult.

PMID- 16817301
TI  - Gonzales v. Oregon and the legitimate purposes of medicine: who gets to decide?

PMID- 16817302
TI  - So, what do I put on this wound? Making sense of the wound dressing puzzle: part
      II.

PMID- 16817304
TI  - Painful memories.

PMID- 16817305
TI  - Screen test.

PMID- 16817306
TI  - Finkelstein's test.

PMID- 16817307
TI  - Changing career.

PMID- 16817308
TI  - A fresh start?

PMID- 16817309
TI  - Getting back in the driving seat.

PMID- 16817310
TI  - Stroke as a clinical emergency.

PMID- 16817311
TI  - Practice makes perfect: intraocular injury.

PMID- 16817312
TI  - Identifying pleuritic chest pain.

PMID- 16817313
TI  - Pain assessment at nurse triage: a literature review.

PMID- 16817314
TI  - Delivering a new intravenous therapy service.

PMID- 16817315
TI  - Why emergency department nurses can find it difficult to ask families and loved
      ones about organ and tissue donation?

PMID- 16817316
TI  - Stress down south: meeting report of the fifth International Workshop on the
      Molecular Biology of Stress Responses.

PMID- 16817318
TI  - Human resting extracellular heat shock protein 72 concentration decreases during
      the initial adaptation to exercise in a hot, humid environment.
AB  - Heat shock protein (Hsp) 72 is a cytosolic protein that also is present in the
      circulation. Extracellular Hsp72 (eHsp72) is inducible by exercise and is
      suggested to act as a danger signal to the immune system. The adaptive response
      of eHsp72 to repeated exercise-heat exposures in humans remains to be determined.
      An intracellular animal study found a reduced Hsp72 response, with no change in
      resting levels, during heat stress after a single day of passive heat
      acclimation. The current study therefore tested whether adaptations in human
      eHsp72 levels would similarly occur 24 hours after a single exercise-heat
      exposure. Seven males completed cycle exercise (42.5% V(O2peak) for 2 hours) in a
      hot, humid environment (38 degrees C, 60% relative humidity) on each of 2
      consecutive days. Blood samples were obtained from an antecubital vein before
      exercise and 0 hours and 22 hours postexercise for the analysis of eHsp72.
      Exercise-heat stress resulted in enhanced eHsp72, with a similar absolute
      increase found on both days (day 1: 1.26 ng/mL [0.80 ng/mL]; day 2: 1.29 ng/mL
      [1.60 ng/mL]). Resting eHsp72 decreased from rest on day 1 to day 2's 22-hour
      postexercise sample (P < 0.05). It is suggested that the reduction in resting
      eHsp72 after 2 consecutive exercise-heat exposures is possibly due to an enhanced
      removal from the circulation, for either immunoregulatory functions, or for
      improved cellular stress tolerance in this initial, most stressful period of
      acclimation.

PMID- 16817317
TI  - On the brotherhood of the mitochondrial chaperones mortalin and heat shock
      protein 60.
AB  - The heat shock chaperones mortalin/mitochondrial heat shock protein 70 (mtHsp70)
      and Hsp60 are found in multiple subcellular sites and function in the folding and
      intracellular trafficking of many proteins. The chaperoning activity of these 2
      proteins involves different structural and functional mechanisms. In spite of
      providing an excellent model for an evolutionarily conserved molecular
      "brotherhood", their individual functions, although overlapping, are
      nonredundant. As they travel to various locations, both chaperones acquire
      different binding partners and exert a more divergent involvement in
      tumorigenesis, cellular senescence, and immunology. An understanding of their
      functional biology may lead to novel designing and development of therapeutic
      strategies for cancer and aging.

PMID- 16817320
TI  - Histidine 89 is an essential residue for Hsp70 in the phosphate transfer
      reaction.
AB  - Autophosphorylation of Hsp70 is detected in the process of substrate refolding in
      the presence of adenosine triphosphate (ATP) in the reaction mixture. But to
      date, the role and mechanism of Hsp70 autophosphorylation have not been
      elucidated. In this study we determined the site of histidine phosphorylation of
      Hsp70 as an intermediate in the process of phosphate transfer reaction by site
      directed mutagenesis. We selected two possible sites (ie, His89 and His227) of
      intermediate histidine phosphorylation based on our hypothesis of the transfer of
      gamma-phosphoryl groups and replacement by glycine and serine. Although an acid
      labile autophosphorylation intermediate of Hsp70 and its cytidine diphosphate
      dependent dephosphorylation were detected in wild-type Hsp70, they were markedly
      suppressed in the H89S mutation of Hsp70, but not on the H227S mutation. The
      ATPase activity and ATP synthesis activity of Hsp70 were almost completely
      suppressed in the H89S and H89G mutations. The role of His89 in the phosphate
      transfer reaction of Hsp70 is discussed.

PMID- 16817319
TI  - Stress-induced phosphorylation of caveolin-1 and p38, and down-regulation of EGFr
      and ERK by the dietary lectin jacalin in two human carcinoma cell lines.
AB  - We have examined the A431 (human epidermoid carcinoma) and HT29 (human colorectal
      carcinoma) cellular responses evoked by lectins of dietary origin, Jacalin of
      Artocarpus integrifolia (native jacalin; nJacalin), peanut agglutinin (PNA) of
      Arachis hypogea, and recombinant single-chain jacalin (rJacalin), which has the
      same protein backbone but approximately 100-fold less affinity for carbohydrates
      than nJacalin. All three lectins (nJacalin, rJacalin, and PNA) are cycotoxic
      inhibitors of proliferation of A431 cells. However, cells recover once jacalin
      but not PNA have been removed from the growth medium. Treatment of nJacalin
      results in morphologically visible cell rounding while retaining the membrane
      integrity when treated at 40 microg ml(-1), but treatment with PNA did not induce
      such changes. The observed cell rounding was found to be due to stress as the
      phosphorylation of caveolin-1 (at tyr14), p38 but not c-Jun N-terminal kinase
      were up-regulated, while PNA did not up-regulate the phosphorylation of the same.
      Jacalin also down-regulated the phosphorylation of the epidermal growth factor
      receptor and extracellular signal regulated kinase in contrast to PNA, which
      failed to down-regulate the same. Confocal microscopic studies reveal that
      jacalin is not internalized, unlike the lectin of Agaricus bisporous. Analysis of
      the proteins that bind to an nJacalin-sepharose column revealed the binding of
      six to eight proteins, and significant among them is a protein at approximately
      110 kDa, which appears to be oxygen-regulated protein 150 (ORP150) (endoplasmic
      reticulum chaperone) as identified by its isoelectric point, two-dimensional
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometric
      analysis. This 110-kDa band is detectable with anti-Hsp70 antibody because ORP150
      has homology with Hsp70. Confocal microscopic studies reveal the presence of
      Hsp70-like proteins on the surface of A431 cells as revealed by immunostaining
      with anti-Hsp70 antibody. Moreover, overexpression of ORP150 in A431 cells has
      resulted in a dramatic protection of A431 cells against jacalin-induced toxicity,
      confirming that the jacalin-induced cytotoxicity is mediated through ORP150, and
      impairment of ORP150 functions with the help of jacalin makes the cells more
      susceptible to death due to stress. Our studies suggest that the cellular
      responses, as a consequence of lectin binding, may not be exclusively mediated by
      carbohydrate binding property alone, but other factors such as protein-protein
      interactions may also contribute to the observed cellular responses.

PMID- 16817321
TI  - Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in
      mammalian cells.
AB  - Because heat shock proteins (Hsps) are involved in protecting cells and in the
      pathophysiology of diseases such as inflammation, cancer, and neurodegenerative
      disorders, the use of regulators of the expression of Hsps in mammalian cells
      seems to be useful as a potential therapeutic modality. To identify compounds
      that modulate the response to heat shock, we analyzed several natural products
      using a mammalian cell line containing an hsp promoterregulated reporter gene. In
      this study, we found that an extract from Fructus Arctii markedly suppressed the
      expression of Hsp induced by heat shock. A component of the extract arctigenin,
      but not the component arctiin, suppressed the response at the level of the
      activation of heat shock transcription factor, the induction of mRNA, and the
      synthesis and accumulation of Hsp. Furthermore, arctigenin inhibited the
      acquisition of thermotolerance in mammalian cells, including cancer cells. Thus,
      arctigenin seemed to be a new suppressive regulator of heat shock response in
      mammalian cells, and may be useful for hyperthermia cancer therapy.

PMID- 16817322
TI  - Overexpressed heat shock protein 70 protects cells against DNA damage caused by
      ultraviolet C in a dose-dependent manner.
AB  - Heat shock protein 70 (Hsp70) comprises proteins that have been reported to
      protect cells, tissues, and organisms against damage from a wide variety of
      stressful stimuli; however, little is known about whether Hsp70 protects against
      DNA damage. In this study, we investigated the relationship between Hsp70
      expression and the levels of ultraviolet C (UVC)-induced DNA damage in A549 cells
      with normal, inhibited, and overexpressed Hsp70 levels. Hsp70 expression was
      inhibited by treatment with quercetin or overexpressed by transfection of
      plasmids harboring the hsp70 gene. The level of DNA damage was assessed by the
      comet assay. The results showed that the levels of DNA damage (shown as the
      percentage of comet cells) in A549 cells increased in all cells after exposure to
      an incident dose of 0, 10, 20, 40, and 80 J/m2 whether Hsp70 was inhibited or
      overexpressed. This response was dose dependent: a protection against UVC-induced
      DNA damage in cells with overexpressed Hsp70 was observed at UVC dose 20 J/m2
      with a maximum at 40 J/m2 when compared with cells with normal Hsp70 levels and
      in quercetin-treated cells. This differential protection disappeared at 80 J/m2.
      These results suggest that overexpressed Hsp70 might play a role in protecting
      A549 cells from DNA damage caused by UVC irradiation, with a threshold of
      protection from at UVC irradiation-induced DNA damage by Hsp70. The detailed
      mechanism how Hsp70 is involved in DNA damage and possible DNA repair warrants
      further investigation.

PMID- 16817323
TI  - In vivo resolution of oligomers with fluorescence photobleaching recovery
      histograms.
AB  - Simple independent enzyme-catalyzed reactions distributed homogeneously
      throughout an aqueous environment cannot adequately explain the regulation of
      metabolic and other cellular processes in vivo. Such an unstructured system
      results in unacceptably slow substrate turnover rates and consumes inordinate
      amounts of cellular energy. Current approaches to resolving compartmentalization
      in living cells requires the partitioning of the molecular species in question
      such that its localization can be resolved with fluorescence microscopy. Standard
      imaging approaches will not resolve localization of protein activity for proteins
      that are ubiquitously distributed, but whose function requires a change in state
      of the protein. The small heat shock protein sHSP27 exists as both dimers and
      large multimers and is distributed homogeneously throughout the cytoplasm. A
      fusion of the green fluorescent protein variant S65T and sHSP27 is used to assess
      the ability of diffusion rate histograms to resolve compartmentalization of the 2
      dominant oligomeric species of sHSP27. Diffusion rates were measured by
      multiphoton fluorescence photobleaching recovery. Under physiologic conditions,
      diffusion rate histograms resolved at least 2 diffusive transport rates within a
      living cell potentially corresponding to the large and small oligomers of sHSP27.
      Given that oligomerization is often a means of regulation, compartmentalization
      of different oligomer species could provide a means for efficient regulation and
      localization of sHsp27 activity.

PMID- 16817324
TI  - Overexpression of inducible heat shock protein 70 and its mutants in astrocytes
      is associated with maintenance of mitochondrial physiology during glucose
      deprivation stress.
AB  - Wild-type inducible Hsp70 (WT) and 2 folding deficient mutants protect the brain
      against focal cerebral ischemia in vivo and brain cells from oxygen-glucose
      deprivation (OGD) in vitro, but the protective mechanisms remain unclear.
      Mitochondria are central to both normal physiological function and the regulation
      of cell death. We tested the effect of overexpressing Hsp70 and 2 mutants, Hsp70
      K71 E, an adenosine triphosphatase (ATPase)-deficient point mutant, and Hsp70-381
      640, a deletion mutant lacking the ATPase domain on mitochondrial physiology
      under glucose deprivation (GD) stress in primary cultured astrocytes.
      Mitochondrial membrane potential was assessed using a potentiometric fluorescent
      dye tetramethylrhodamine ethyl ester (TMRE). By 5 hours of GD, the mitochondria
      in the LXSN control transfected astrocytes had markedly reduced membrane
      potential. However, in the Hsp70-WT, -K71E, and -381-640 groups, there was no
      apparent change in TMRE signal during 5 hours of GD. Oxygen consumption was
      measured to assess oxidative respiration. Overexpression of Hsp70-K71 E and -381
      640 prevented the decrease in state III respiration observed at 5 hours, and all
      3 prevented the increase in state IV respiration found in LXSN controls after 5
      hours of GD. Reactive oxygen species (ROS) production was assessed with
      hydroethidine. Hsp70 and its mutants all significantly reduced the increases in
      ROS accumulation during 5 hours of GD. The results demonstrate that the
      protective effect of the carboxyl-terminal half of Hsp70 and of the full-length
      molecule is associated with better maintained mitochondrial membrane potential,
      better maintained state IV respiration, and reduced ROS generation during GD.

PMID- 16817326
TI  - Intra-European differences in the radiotherapeutic management of breast cancer: a
      survey study.
AB  - AIMS: To document and explain self-reported practices of the radiotherapeutic
      management of breast cancer within different European regions. METHODS: An
      original survey questionnaire was developed to assess radiation oncologists' self
      reported management of breast cancer. The questionnaire was distributed to
      physician members of the American Society for Therapeutic Radiology and Oncology
      and the European Society of Therapeutic Radiation Oncology. This paper presents
      the results of the comparative analysis of 702 responses from North America and
      435 responses from Europe. RESULTS: Several areas of variation are identified.
      These include the selection criteria for post-mastectomy radiation and radiation
      for ductal carcinoma in situ (DCIS). Variations are also seen in the management
      of regional lymph nodes after lumpectomy, and radiation dose and fractionation.
      CONCLUSIONS: Radiation oncologists within Europe vary in their self-reported
      practices for managing women with breast cancer. These differences may be rooted
      in deeper cultural differences and differences in the healthcare systems of
      different European countries. They may also reflect differences in the relative
      weight radiation oncologists place upon data generated within their own
      countries. These results support the need for co-operative group trials to
      provide evidence for more uniform treatment recommendations and policies.

PMID- 16817325
TI  - The function of the beta3 interactive domain in the small heat shock protein and
      molecular chaperone, human alphaB crystallin.
AB  - Knowledge of the interactive domains on the surface of small heat shock proteins
      (sHSPs) is necessary for understanding the assembly of complexes and the activity
      as molecular chaperones. The primary sequences of 26 sHSP molecular chaperones
      were aligned and compared. In the interactive beta3 sequence, 73DRFSVNLDVKHFS85
      of human alphaB crystallin, Ser-76, Asn-78, Lys-82, and His-83 were identified as
      nonconserved residues on the exposed surface of the alpha crystallin core domain.
      Site-directed mutagenesis produced the mutant alphaB crystallins: S76E, N78G,
      K82Q, and H83F. Domain swapping with homologous beta3 sequences,
      32EKFEVGLDVQFFT44 from Caenorhabditis elegans sHSP12.2 or 69DKFVIFLDVKHFS81 from
      alphaA crystallin, resulted in the mutant alphaB crystallins, CE1 and alphaA1,
      respectively. Decreased chaperone activity was observed with the point mutants
      N78G, K82Q, and H83F and with the mutant, CE1, in aggregation assays using betaL
      crystallin, alcohol dehydrogenase (ADH), or citrate synthase (CS). The S76E
      mutant had minimal effect on chaperone activity, and domain swapping with alphaA
      crystallin had no effect on chaperone activity. The mutations that resulted in
      altered chaperone activity, produced minimal modification to the secondary,
      tertiary, and quaternary structure of human alphaB crystallin as determined by
      ultraviolet circular dichroism spectroscopy, chymotrypsin proteolysis, and size
      exclusion chromatography. Chaperone activity was influenced by the amount of
      unfolding of the target proteins and independent of complex size. The results
      characterized the importance of the exposed side chains of Glu-78, Lys-82, and
      His-83 in the interactive beta3 sequence of the alpha crystallin core domain in
      alphaB crystallin for chaperone function.

PMID- 16817327
TI  - Clinical trials and modern advertising: the lung cancer trials flowchart.

PMID- 16817328
TI  - Small cell lung cancer treated in southeast Wales.
AB  - AIMS: In small cell lung cancer (SCLC), consolidation thoracic irradiation (CTI)
      increases 3-year absolute survival by 5.4% in patients with limited disease and a
      complete response to chemotherapy. Early concurrent thoracic radiotherapy has
      been shown to improve local control and prolong survival compared with CTI in
      some trials. The standard management of patients with SCLC in southeast Wales is
      CTI in individuals with limited disease and a complete response to chemotherapy.
      A review of patients with SCLC was carried out to establish whether survival
      locally is comparable with that reported in published studies, and if patients
      given CTI have survival comparable with that reported in studies where early
      concurrent thoracic radiotherapy was used. MATERIALS AND METHODS: Between January
      2000 and December 2002, 303 patients were registered with SCLC in southeast
      Wales. One hundred and fifteen (47%) patients had limited disease and 60/115
      (52%) received CTI. RESULTS: Patients with limited disease receiving CTI had a
      median survival of 17.7 months (95% confidence interval: 15-27.9 months). The 2-
      and 5-year survivals were 38 and 13%, respectively. CONCLUSIONS: These results
      compare favourably with previously published studies on SCLC. There are no plans
      to change our current treatment policy for SCLC in southeast Wales.

PMID- 16817329
TI  - Radical radiotherapy in head and neck squamous cell carcinoma: an analysis of
      prognostic and therapeutic factors.
AB  - AIMS: Head and neck squamous cell carcinoma (HNSCC) continues to be a leading
      cancer in developing countries. Definitive radiation therapy either primary or as
      postoperative adjuvant is offered to most patients. We aimed to identify
      prognostic and therapeutic factors that affect locoregional control and survival
      in patients undergoing radical radiotherapy for head and neck squamous cell
      cancers. MATERIALS AND METHODS: A retrospective analysis of 568 previously
      untreated patients with squamous head and neck cancers, who received radical
      radiotherapy between 1990 and 1996, using local control, locoregional control and
      disease-free survival (DFS) as outcome measures. RESULTS: With a median follow-up
      of 18 months for living patients, the 5-year local control, locoregional control
      and DFS for all 568 patients were 53%, 45% and 41%, respectively, for all stages
      combined. The 5-year local control, locoregional control and DFS as per the
      American Joint Committee on Cancer stage grouping were 78%, 70% and 70%; 64%, 59%
      and 57%; 51%, 42% and 37%; and 40%, 27% and 22% from stages I to IV,
      respectively, with highly significant P values. Patients receiving higher doses
      (> or = 66 Gy) had a significantly better outcome compared with lower doses. The
      5-year local control (59% vs 48%, P = 0.0015), locoregional control (47% vs 41%;
      P = 0.0043) and DFS (44% vs 37%; P = 0.0099) were significantly better in
      patients receiving > or = 66 Gy. Site of primary also affected outcome
      significantly, with oral cavity lesions faring badly. CONCLUSION: Tumour stage
      remains the most important factor affecting outcome in radical radiotherapy of
      HNSCC. A definite dose-response relationship exists with higher total doses,
      leading to better local control, locoregional control and DFS in all stages. Site
      of primary affects outcome too, with laryngeal primaries doing well and oral
      cavity cancers faring the worst.

PMID- 16817331
TI  - Can I look at my list? An evaluation of a 'prompt sheet' within an oncology
      outpatient clinic.
AB  - AIMS: We introduced a patient 'prompt sheet' into our clinic between January 2004
      and January 2005. The aim was to determine whether it would facilitate
      communication and help patients in obtaining their desired level of information
      about their illness, and assist with decision making. We conducted an audit
      survey to investigate the way follow-up takes place in our oncology clinic, to
      determine what works and what does not work in the clinic, and to examine how
      patients access the most useful information and to assess the utility of, and
      patient satisfaction with, a locally developed pilot prompt sheet. MATERIALS AND
      METHODS: A single questionnaire was designed to elicit information on patients'
      information needs, overall satisfaction with the oncology clinic, and uptake and
      perceived usefulness of the prompt sheet. We carried out an audit survey in the
      form of a Likert-scale questionnaire (33 questions), followed immediately
      afterwards by a semi-structured interview. A specialist nurse asked a range of
      open questions about what was good and bad about the clinic and the prompt
      sheets. RESULTS: Despite efforts to ensure that all patients received the prompt
      sheet leaflets, only 254 out of 300 (85%) received them. Of these, 195 (65%) felt
      that they were 'very helpful', and 30 (10%) found them 'fairly helpful'. However,
      15 (5%) had no strong feelings and only three found them either fairly or
      completely unhelpful. One-third of the patients were able to ask more questions
      about their disease as a result of the prompt sheet, although they felt the
      doctor was busy and did not want to take up too much of their time. Men with
      prostate cancer found the prompt sheet particularly helpful to ask questions.
      CONCLUSION: This satisfaction audit suggests that our pilot prompt sheet is
      helpful to patients attending oncology outpatient appointments, particularly for
      men with prostate cancer. We aim to adapt the present prompt sheet on the basis
      of the replies obtained, and re-audit in the future.

PMID- 16817330
TI  - Primary radical radiotherapy for squamous cell carcinoma of the middle ear and
      external auditory cana--an historical series.
AB  - AIMS: To evaluate patients treated with radical radiotherapy alone for squamous
      cell carcinoma of the middle ear (MEC) and external auditory canal (EAC) in terms
      of freedom from local recurrence, cancer-specific survival and morbidity.
      MATERIALS AND METHODS: Between 1965 and 1988, 123 patients were treated, 70 with
      MEC and 53 with EAC. The median age was 64 years (range 21-86) and 78% presented
      as late stage. The median dose was 55 Gy (range 39-55) in 16 once daily fractions
      (range 13-21). RESULTS: At 5 and 10 years, respectively, freedom from local
      recurrence was 56 and 56%, disease-free survival was 45 and 43%, cancer-specific
      survival was 53 and 51%, and overall survival was 40 and 21%. Cancer-specific
      survival was significantly worse with late stage as opposed to early stage (P =
      0.0026), as was local recurrence (P = 0.0088). No differences in survival and
      local control were seen according to site. Radionecrosis developed in 6% of
      patients. CONCLUSIONS: Combined treatment using radiotherapy and radical surgery
      is often favoured. This large series shows that radical radiotherapy achieves
      comparable results in terms of local control and cancer-specific survival. Our
      radiotherapy regimen is now 55 Gy in 20 daily fractions to reduce late morbidity.
      Radiotherapy alone remains a viable option, especially as morbidity can be
      minimised and target volume delineation optimised using computer planning in the
      future.

PMID- 16817332
TI  - Waiting times for cancer surgery in Ontario: 1984-2000.
AB  - AIMS: Despite persistent public interest and the perception among clinicians and
      patients that increased waiting time for cancer surgery is related to worse
      outcomes, little is known about waiting time for cancer surgery. Our aim is to
      describe changes in waiting times for cancer surgery in Ontario between 1984 and
      2000, and associated factors. MATERIALS AND METHODS: The interval between date of
      diagnosis and admission for surgery for all patients receiving surgical treatment
      for cancers of the larynx, hypopharynx, stomach, colon, rectum, breast, cervix,
      uterus, prostate, bladder, lung and oesophagus was calculated for all patients in
      Ontario between 1984 and June 2000. This was accomplished by retrospective review
      of prospectively gathered electronic records. RESULTS: Median waiting times for
      cancer surgery increased for all cancer types, including substantial increases
      for oesophageal cancer (from 14 days between 1984 and 1987 to 33 days between
      1998 and 2000), breast cancer (12-27 days), and laryngeal cancer (16-33 days). A
      similar increase in waiting times for patients awaiting radiation therapy was
      identified. The proportion of patients receiving diagnosis and definitive
      resection on the same admission for colon cancer decreased (from 79.4% between
      1984 and 1987 to 47.9% between 1998 and 2000) for laryngeal cancer (35.5-9.4%),
      and for lung cancer (61.6-23.0%). Age, sex, cancer site, hospital type, household
      income and cancer centre location were all independently related to waiting
      times. CONCLUSIONS: Waiting times for cancer surgery increased substantially
      between 1984 and 2000. Waiting times were influenced by disease, patient and
      health-system-related factors.

PMID- 16817333
TI  - An electrodiagnostic evaluation of the effect of pre-existing peripheral nervous
      system disorders in patients treated with the novel proteasome inhibitor
      bortezomib.
AB  - AIMS: Bortezomib (Velcade), a novel proteasome inhibitor, has shown promise in
      the treatment of malignancies, including multiple myeloma and non-Hodgkin's
      lymphoma. Several studies have identified neuropathy as a potentially dose
      limiting side effect of treatment with bortezomib. We report the clinical and
      electrodiagnostic data from four patients who developed signs and symptoms of
      peripheral neuropathy from treatment with bortezomib. MATERIALS AND METHODS:
      Patients were included if they were enrolled in active phase 2 trials of
      bortezomib for non-Hodgkin's lymphoma or prostate cancer, developed signs and
      symptoms of peripheral neuropathy, and were referred for electrodiagnostic
      evaluation. RESULTS: Four patients, including two with non-Hodgkin's lymphoma and
      two with prostate cancer, underwent electrodiagnostic testing. Electrodiagnostic
      evaluation showed pre-existing peripheral nervous system disorders in three out
      of four patients. Multiple peripheral nervous system disorders were present in
      two out of four patients. CONCLUSIONS: Bortezomib can cause a predominately
      sensory axonal polyneuropathy. Pre-existing peripheral nervous system disorders,
      such as neuropathy and radiculopathy, are common in patients with cancer, and may
      pre-dispose to the development of symptomatic neuronal toxicity when treated with
      bortezomib. Baseline electrodiagnostic evaluation may identify patients with pre
      existing peripheral nervous system disorders at risk for additive neuronal
      toxicity from neurotoxic chemotherapeutic agents.

PMID- 16817334
TI  - Late radiotherapy effects: is bowel morbidity adequately documented or patients'
      needs managed appropriately?

PMID- 16817335
TI  - Response to cetuximab and gemcitabine-oxaliplatin in an advanced case of
      intrahepatic cholangiocarcinoma.

PMID- 16817336
TI  - A case of advanced scalp angiosarcoma successfully treated with combination
      chemotherapy of adriamycin, cisplatin and ifosfamide.

PMID- 16817337
TI  - Radiation-induced lumbo-sacral plexopathy (RILSP): an important enigma.

PMID- 16817338
TI  - [Primary hyperparathyroidism].

PMID- 16817339
TI  - [Asymptomatic hyperparathyroidism].

PMID- 16817340
TI  - [Familial hyperparathyroidism].

PMID- 16817341
TI  - [Neonatal hyperparathyroidism].

PMID- 16817342
TI  - [Hyperparathyroidism--jaw tumor syndrome].

PMID- 16817343
TI  - [Parathyroid cancer].

PMID- 16817344
TI  - [Secondary hyperparathyroidism].

PMID- 16817345
TI  - [Idiopathic hypoparathyroidism].

PMID- 16817346
TI  - [Familial isolated hypoparathyroidism].

PMID- 16817347
TI  - [DiGeorge syndrome].